PMID- 11221826
TI  - Electroporation-mediated interleukin-12 gene therapy for hepatocellular carcinoma
      in the mice model.
AB  - Applications of nonviral vectors for gene transfer into tumors in vivo have been
      limited by the relatively low expression levels of the transferred gene. The aim
      of this study is to evaluate the efficacy of electroporation-mediated interleukin
      12 (IL-12) gene therapy for hepatocellular carcinoma (HCC). First, we
      investigated the optimal conditions of electric pulses (voltage, pulsing
      duration, numbers of shocks) of in vivo electroporation for gene transfer into
      HCC established by s.c. implantation of MH134 cells to C3H mice. This process
      made use of plasmid DNA that express the luciferase gene. We concluded that the
      optimal conditions for the electric pulses are as follows: voltage at 150 V;
      pulsing duration at 50 ms; nonpulsing duration at 950 ms; and the number of
      shocks at 10. Second, we tried to treat s.c. HCC by electroporation using plasmid
      DNA that expresses the murine interleukin-12 (mlL-12) gene. Intratumoral
      administration of the mIL-12 vector elevated serum IL-12 and IFN-gamma and
      significantly inhibited the growth not only of HCC into which the mIL-12 vector
      had been directly transferred, but also of the distant HCC. In addition,
      intratumoral administration of the mIL-12 vector inhibited spontaneous lung
      metastasis and delayed establishment of HCC injected 3 days after mIL-12 gene
      therapy. The IL-12 gene therapy induced more lymphocyte infiltration by NK cells,
      CD3+ cells, and Mac-1 positive cells into the tumor and reduced the number of
      microvessels. Therefore, more terminal deoxynucleotidyl transferase-mediated dUTP
      nick end labeling-positive tumor cells were found. These results demonstrate that
      gene therapy for HCC by electroporation in vivo using IL-12 is very efficient and
      is thus promising for further clinical trial.

PMID- 11221827
TI  - In vitro and in vivo anticancer activities of synthetic macrocyclic ketone
      analogues of halichondrin B.
AB  - Halichondrin B is a highly potent anticancer agent originally found in marine
      sponges. Although scarcity of the natural product has hampered efforts to develop
      halichondrin B as a new anticancer drug, the existence of a complete synthetic
      route has allowed synthesis of structurally simpler analogues that retain the
      remarkable potency of the parent compound. In this study, we show that two
      macrocyclic ketone analogues of halichondrir B, ER-076349 and ER-086526, have sub
      nM growth inhibitory activities in vitro against numerous human cancer cell lines
      as well as marked in vivo activities at 0.1-1 mg/kg against four human
      xenografts: MDA-MB-435 breast cancer, COLO 205 colon cancer, LOX melanoma, and
      NIH: OVCAR-3 ovarian cancer. ER-076349 and ER-086526 induce G2-M cell cycle
      arrest and disruption of mitotic spindles, consistent with the tubulin-based
      antimitotic mechanism of halichondrin B. This is supported further by direct
      binding of the biotinylated analogue ER-040798 to tubulin and inhibition of
      tubulin polymerization in vitro by ER-076349 and ER-086526. Retention of the
      extraordinary in vitro and in vivo activity off halichondrin B in structurally
      simplified, fully synthetic analogues establishes the feasibility of developing
      halichondrin B-based agents as highly effective, novel anticancer drugs.

PMID- 11221828
TI  - Metastatin: a hyaluronan-binding complex from cartilage that inhibits tumor
      growth.
AB  - In this study, a hyaluronan-binding complex, which we termed Metastatin, was
      isolated from bovine cartilage by affinity chromatography and found to have both
      antitumorigenic and antiangiogenic properties. Metastatin was able to block the
      formation of tumor nodules in the lungs of mice inoculated with B16BL6 melanoma
      or Lewis lung carcinoma cells. Single i.v. administration of Metastatin into
      chicken embryos inhibited the growth of both B16BL6 mouse melanoma and TSU human
      prostate cancer cells growing on the chorioallantoic membrane. The in vivo
      biological effect may be attributed to the antiangiogenic activity because
      Metastatin is able to inhibit the migration and proliferation of cultured
      endothelial cells as well as vascular endothelial growth factor-induced
      angiogenesis on the chorioallantoic membrane. In each case, the effect could be
      blocked by either heat denaturing the Metastatin or premixing it with hyaluronan,
      suggesting that its activity critically depends on its ability to bind hyaluronan
      on the target cells. Collectively, these results suggest that Metastatin is an
      effective antitumor agent that exhibits antiangiogenic activity.

PMID- 11221829
TI  - Dual antitumor effects of 5-fluorouracil on the cell cycle in colorectal
      carcinoma cells: a novel target mechanism concept for pharmacokinetic modulating
      chemotherapy.
AB  - 5-Fluorouracil (5-FU) is one of the most widely used anticancer agents for
      advanced colorectal carcinoma, but its response rate is only 15%. The
      "pharmacokinetic modulating chemotherapy" (PMC) regimen that we have advocated
      has proved to be highly effective in treating colorectal carcinoma. PMC consists
      of a continuous i.v. infusion of 5-FU over 24 h for 1day a week at 600 mg/m2/day,
      and an oral dose of uracil-tegafur (UFT), a 5-FU derivative, at 400 mg/day for 5
      7 days per week, repeated every week for more than 6 months. Assays of 5-FU in 23
      patients receiving this treatment showed serum concentrations ranging from 88 to
      1,323 ng/ml. We then analyzed the effects of clinically relevant concentrations
      of 5-FU found in colorectal cancer patients treated with the PMC regimen on the
      growth of three human colorectal adenocarcinoma cell lines, SW480 and COLO320DM
      (mutant p53) and HCT116 (wild-type p53). Exposure of these three cell lines to 5
      FU resulted in growth inhibition in a dose-dependent manner. Exposure to 100
      ng/ml of 5-FU in SW480 and COLO320DM caused G1 arrest after 24 h and G2 arrest
      after 72-144 h, and only a minority of the cell population showed apoptotic
      features, which indicated that most of the cells were killed through mitotic
      catastrophe, nonapoptotic cell death. On the contrary, exposure to 1000 ng/ml of
      5-FU in SW480 and COLO320DM resulted in G1-S-phase arrest and the induction of
      apoptosis throughout the experimental period. Nuclear cyclin B1 expression was
      markedly induced with exposure to 100 ng/ml of 5-FU in SW480 and COLO320DM; and
      expression of 14-3-3sigma protein, a cell cycle inhibitor in the GG phase, was
      induced in SW480. ICT116 responded to lower concentrations of 5-FU more rapidly:
      G2 arrest was seen after 24-72 h of exposure to 10 ng/ml of 5-FU, and G,1rrest
      was seen after 12-24 h of exposure to 100 ng/ml. These results show that 5-FU
      acts via two different pathways, depending on dose: (a) G,1S-phase cell cycle
      arrest and apoptosis at 1,000 ng/ml in SW480 and COLO320DM, and 100 ng/ml in
      HCT116; and (b) G2-M-phase cell cycle arrest and mitotic catastrophe at 100 ng/ll
      in SW480 and COLO320DM, and 10 ng/ml in HCT116. These results suggest that the
      efficacy of our PMC regimen is based on targeting at least two different phases
      of the cell cycle. In our clinical trial, we showed efficacy independent of p53
      status, ascertained by cell kinetic analysis in vitro, which may lead to a novel
      concept of schedule-oriented biochemical modulation of this drug.

PMID- 11221830
TI  - Anticancer drugs induce increased mitochondrial cytochrome c expression that
      precedes cell death.
AB  - Recent studies have demonstrated that cytochrome c plays an important role in
      cell death. In the present study, we report that teniposide and various other
      chemotherapeutic agents induced a dose-dependent increase in the expression of
      the mitochondrial respiratory chain proteins cytochrome c, subunits I and IV of
      cytochrome c oxidase, and the free radical scavenging enzyme manganous superoxide
      dismutase. The teniposide-induced increase of cytochrome c was inhibited by
      cycloheximide, indicating new protein synthesis. Elevated cytochrome c levels
      were associated with enhanced cytochrome c oxidase-dependent oxygen uptake using
      TMPD/ascorbate as the electron donor, suggesting that the newly synthesized
      proteins were functional. Cytochrome c was released into the cytoplasm only after
      maximal levels had been reached in the mitochondria, but there was no concomitant
      decrease in mitochondrial membrane potential or caspase activation. Our results
      suggest that the increase in mitochondrial protein expression may play a role in
      the early cellular defense against anticancer drugs.

PMID- 11221831
TI  - Tumor necrosis factor alpha sensitizes low epidermal growth factor receptor
      (EGFR)-expressing carcinomas for anti-EGFR therapy.
AB  - Analysis of 1,060 xenotransplants derived from cancer cell lines as wel as
      spontaneously occurring tumors from the larynx, pharynx, mammary gland, uterine
      cervix, and vulva revealed that tumor regression induced by treatment with
      monoclonal antibodies (EMD 55900 and EMD 72000 against the epidermal growth
      factor receptor (EGFR) could be enhanced by tumor necrosis factor alpha (TNF
      alpha) treatment in vivo. Moreover, tumor that primarily do not respond to
      antibody treatment can be made suscep tible by additional TNF-alpha treatment. To
      investigate the in vivo effects of monoclonal antibodies, we treated tumors
      derived from cell lines (A431 and Detroit 562) as well as spontaneously occurring
      squamous cell carci nomas and adenocarcinomas (transplanted on NMRI-nu/nu mice)
      gener ally with EMD 55900 (40 microg/g mouse) and its humanized version EMD 72000
      (40 microg/g mouse). When treated with EMD 55900 and EMD 72000 carcinomas with an
      EGFR concentration of > or = 70 fmol/mg protein showed significant reduction in
      tumor size compared with untreated controls. The degree of tumor regression
      correlated with the EGFR concentration of the tumor. In mice treated with TNF
      alpha (0.5 microg/g mouse) and EMD 55900 72000 simultaneously, we observed
      enhanced antitumor effects up to complete tumor eradication. Carcinomas with an
      EGFR concentration <70 fmol/mg protein could be made susceptible to treatment
      with EMD 55900 and EMD 72000 by simultaneous treatment with TNF-alpha, resulting
      in a significant reduction in tumor size.

PMID- 11221832
TI  - Triggering of antitumor activity through melanoma-specific transduction of a
      constitutively active tumor necrosis factor (TNF) R1 chimeric receptor in the
      absence of TNF-alpha.
AB  - Tumor necrosis factor-alpha (TNF-alpha) has been intensively studied because of
      the specific toxicity of this cytokine toward cells that undergo malignant
      transformation. However, its proinflammatory and immunoregulatory properties
      always represented a drawback to the TNF-alpha administration in cancer therapy.
      In this study, we describe an adenovirus-based strategy in which the tumoricidal
      activity of TNF-alpha can be selectively triggered to eradicate tumors without
      administering TNF-alpha. This strategy might allow us to prevent TNF-alpha
      effects on normal tissues and, therefore, to bypass its systemic toxic effects.
      We inserted the constitutively active version of the Mr 55,000 TNF receptor,
      which was shown previously (F. Bazzoni et al., Proc. Natl. Acad. Sci. USA, 92:
      5376-5380, 1995) to be capable of killing cells upon expression in the absence of
      its ligand, into a replication-deficient adenovirus, and under the control of a
      melanoma-specific promoter/enhancer element. We show that, upon infection, the
      recombinant gene reaches high level of expression in melanoma cell lines and
      triggers apoptosis by activating the caspase cascade. Expression and function of
      this receptor is restricted to melanoma cell lines, because morphology,
      viability, and proliferation of other cell types exposed to the recombinant
      adenovirus infection are not affected. We show for the first time that a TNF-like
      apoptotic response can be triggered in the absence of TNF-alpha and can be
      selectively confined to specific cellular targets. Killing activity and tissue
      specificity of the recombinant TNF receptor adenovirus, together with the
      advantage of triggering a TNF-like antitumor activity in the absence of TNF-alpha
      itself, are ideal features for a vector that might be the choice for gene therapy
      aimed to eradicate malignant cells.

PMID- 11221833
TI  - Characterization of metabolites of the chemopreventive agent curcumin in human
      and rat hepatocytes and in the rat in vivo, and evaluation of their ability to
      inhibit phorbol ester-induced prostaglandin E2 production.
AB  - Curcumin, the yellow pigment in turmeric, has been shown to prevent malignancies
      in a variety of tissues in rodents, especially in the intestinal tract.
      Pharmacological activities of curcumin in cells in situ germane to
      chemoprevention, such as inhibition of expression of cyclooxygenase-2 (COX-2),
      require drug concentrations in the 10(-5) - 10(-4) M range. The systemic
      bioavailability of curcumin is low, so that its pharmacological activity may be
      mediated, in part, by curcumin metabolites. To investigate this possibility, we
      compared curcumin metabolism in human and rat hepatocytes in suspension with that
      in rats in vivo. Analysis by high-performance liquid chromatography with
      detection at 420 and 280 nm permitted characterization of metabolites with both
      intact diferoylmethane structure and increased saturation of the heptatrienone
      chain. Chromatographic inferences were corroborated by mass spectrometry. The
      major metabolites in suspensions of human or rat hepatocytes were identified as
      hexahydrocurcumin and hexahydrocurcuminol. In rats, in vivo, curcumin
      administered i.v. (40 mg/kg) disappeared from the plasma within 1 h of dosing.
      After p.o. administration (500 mg/kg), parent drug was present in plasma at
      levels near the detection limit. The major products of curcumin biotransformation
      identified in rat plasma were curcumin glucuronide and curcumin sulfate whereas
      hexahydrocurcumin, hexahydrocurcuminol, and hexahydrocurcumin glucuronide were
      present in small amounts. To test the hypothesis that curcumin metabolites
      resemble their progenitor in that they can inhibit COX-2 expression, curcumin and
      four of its metabolites at a concentration of 20 microM were compared in terms of
      their ability to inhibit phorbol ester-induced prostaglandin E2 (PGE2) production
      in human colonic epithelial cells. Curcumin reduced PGE2 levels to preinduction
      levels, whereas tetrahydrocurcumin, previously shown to be a murine metabolite of
      curcumin, hexahydrocurcumin, and curcumin sulfate, had only weak PGE2 inhibitory
      activity, and hexahydrocurcuminol was inactive. The results suggest that (a) the
      major products of curcumin biotransformation by hepatocytes occur only at low
      abundance in rat plasma after curcumin administration; and (b) metabolism of
      curcumin by reduction or conjugation generates species with reduced ability to
      inhibit COX-2 expression. Because the gastrointestinal tract seems to be exposed
      more prominently to unmetabolized curcumin than any other tissue, the results
      support the clinical evaluation of curcumin as a colorectal cancer
      chemopreventive agent.

PMID- 11221834
TI  - S-Phase arrest by nucleoside analogues and abrogation of survival without cell
      cycle progression by 7-hydroxystaurosporine.
AB  - The mechanisms of resistance to nucleoside analogues established in preclinical
      models are rarely found in primary tumors resistant to therapy with these agents.
      We tested the hypothesis that cells sense sublethal incorporation of analogues
      into DNA during replication and react by arresting further DNA synthesis and cell
      cycle progression. After removal of drug, cells may be able to repair damaged DNA
      and continue proliferation, thus escaping nucleoside analogue toxicity. As a
      corollary, we evaluated whether dysregulation of this mechanism causes cell
      death. Using gemcitabine as a model of S-phase-specific nucleoside analogues in
      human acute myelogenous leukemia ML-1 cells, we found that DNA synthesis
      decreased, cells arrested in S-phase transit, and 60-70% of the population
      accumulated in S-phase in response to cytostatic conditions. Proliferation
      continued after washing the cells into drug-free medium. S-phase-arrested cells
      were then treated with otherwise nontoxic concentrations of UCN-01, which caused
      rapid onset of apoptosis without cell cycle progression specifically in cells
      with an S-phase DNA content. Thus, S-phase arrest by nucleoside analogues
      sensitizes cells to UCN-01, which appears to activate signaling for death
      mechanisms and/or inhibit survival pathways. These results differ from those in
      cells arrested at the G2 checkpoint, in which UCN-01 abrogates cell cycle arrest,
      permitting cells to progress in the cell cycle before apoptosis.

PMID- 11221835
TI  - Inhibition of N-myc expression and induction of apoptosis by iron chelation in
      human neuroblastoma cells.
AB  - Neuroblastoma is the second most common solid malignancy of childhood. Enhanced
      expression of the amplified N-myc gene in the tumor cells may be associated with
      poor patient prognosis and may contribute to tumor development and progression.
      The use of deferoxamine mesylate (DFO), an iron chelator, to treat neuroblastoma
      is being investigated in national clinical studies. We show here by TUNEL assay
      and DNA laddering that DFO induces apoptosis in cultured human neuroblastoma
      cells, which is preceded by a decrease in the expression of N-myc and the altered
      expression of some other oncogenes (up-regulating c-fos and down-regulating c
      myb) but not housekeeping genes. The decrease in N-myc expression is iron
      specific but does not result from inhibition of ribonucleotide reductase, because
      specific inhibition of this iron-containing enzyme by hydroxyurea does not affect
      N-myc protein levels. Nuclear run-on and transient reporter gene expression
      experiments show that the decrease in N-myc expression occurs at the level of
      initiation of transcription and by inhibiting N-myc promoter activity. Comparison
      across neuroblastoma cell lines of the amount of residual cellular N-myc protein
      with the extent of apoptosis measured as pan-caspase activity after 48 h of iron
      chelation reveals no correlation, suggesting that the decrease in N-myc
      expression is unlikely to mediate apoptosis. In conclusion, chelation of cellular
      iron by DFO may alter the expression of multiple genes affecting the malignant
      phenotype by multiple pathways. Given the clinical importance of N-myc
      overexpression in neuroblastoma malignancy, decreasing N-myc expression by DFO
      might be useful as an adjunct to current

PMID- 11221836
TI  - Enhancement of DNA vaccine potency by linkage of antigen gene to a gene encoding
      the extracellular domain of Fms-like tyrosine kinase 3-ligand.
AB  - Recently, Flt3 (Fms-like tyrosine kinase 3)-ligand has been identified as an
      important cytokine for the generation of professional antigen-presenting cells
      (APCs), particularly dendritic cells (DCs). A recombinant chimera of the
      extracellular domain of Flt3-ligand (FL) linked to a model antigen may
      potentially target the antigen to DCs and their precursor cells. Using human
      papillomavirus-16 E7 as a model antigen, we evaluated the effect of linkage to FL
      on the potency of antigen-specific immunity generated by naked DNA vaccines
      administered intradermally via gene gun. We found that vaccines containing
      chimeric FL-E7 fusion genes significantly increased the frequency of E7-specific
      CD8+ T cells relative to vaccines containing the wild-type E7 gene. In vitro
      studies indicated that cells transfected with FL-E7 DNA presented E7 antigen
      through the MHC class I pathway more efficiently than wild-type E7 DNA.
      Furthermore, bone marrow-derived DCs pulsed with cell lysates containing FL-E7
      fusion protein presented E7 antigen through the MHC class I pathway more
      efficiently than DCs pulsed with cell lysates containing wild-type E7 protein.
      More importantly, this fusion converted a less effective vaccine into one with
      significant potency against established E7-expressing metastatic tumors. The FL
      E7 fusion vaccine mainly targeted CD8+ T cells, and antitumor effects were
      completely CD4 independent. These results indicate that fusion of a gene encoding
      the extracellular domain of FL to an antigen gene may greatly enhance the potency
      of DNA vaccines via CD8-dependent pathways.

PMID- 11221837
TI  - Use of an in vitro immunoselected tumor line to identify shared melanoma antigens
      recognized by HLA-A*0201-restricted T cells.
AB  - An immunoselected melanoma cell line that had lost expression of the dominant
      melanoma antigens MART-1 and gp100 was generated in an attempt to identify
      previously unknown tumor antigens. After repeated stimulation with the autologous
      immunoselected tumor line, a number of HLA-A*0201-restricted T-cell clones were
      established from the peripheral blood of a single melanoma patient. One T-cell
      clone (C-22) recognized 14 of 16 HLA-A2+ melanoma cell lines, as well as HLA-A2+
      melanocytes but recognized neither HLA-A2+ fibroblasts nor autologous B cells.
      Screening of an autologous cDNA library resulted in the isolation of a transcript
      identical to an entry in the expressed sequence tag database. Northern blot
      analysis revealed that this gene was expressed in most melanoma cell lines and
      melanocytes but not in normal tissues. The peptide epitope (AMF-GREFCYA)
      recognized by clone C-22 was identified based on studies of the recognition of
      truncated cDNAs and the use of the consensus HLAA*0201 binding motif. A second T
      cell clone (C-29) was found to recognize a new tyrosinase-related protein 2
      epitope (455-463; YAIDLPVSV) in an HLA-A*0201-restricted manner. Together, these
      results provide additional targets that can be used for the development of
      immunotherapeutic protocols in HLA-A2+ melanoma patients and demonstrate the
      utility of immunoselected tumor lines for the identification of new melanoma
      antigens.

PMID- 11221838
TI  - Characterization of the major histocompatibility complex class I deficiencies in
      B16 melanoma cells.
AB  - The murine B16 melanoma system represents an important in vivo model for the
      evaluation of T cell-based immunization and vaccination strategies, although
      deficient MHC class I surface expression has been identified in these cells. We
      postulate here that the MHC class I-deficient phenotype of B16 melanoma cells is
      attributable to down-regulation or the loss of the expression and function of
      multiple components of the MHC class I antigen-processing pathway, including the
      peptide transporter associated with antigen processing, the proteasome subunits
      LMP2, LMP7, and LMP10, PA28alpha and -beta, and the chaperone tapasin. In
      contrast, calnexin, calreticulin, ER60, and protein disulfide isomerase
      expression are unaltered or only marginally suppressed in these cells. The level
      of down-regulation of the components of the antigen-processing pathway is either
      transcriptionally or posttranscriptionally controlled and could be corrected in
      all cases by IFN-y treatment, which also reconstituted MHC class I surface
      expression. Thus, B16 melanoma cells can be used as a model for the
      characterization of the mechanisms underlying the coordinated dysregulation of
      the antigen-processing components, which should provide new insights into the
      development of tumors and the factors controlling this process.

PMID- 11221839
TI  - Macrophage arginase promotes tumor cell growth and suppresses nitric oxide
      mediated tumor cytotoxicity.
AB  - Macrophages use L-arginine to synthesize nitric oxide (NO) and polyamines through
      the inducible NO synthase (iNOS) and arginase, respectively. The released NO
      contributes to the tumoricidal activity of macrophages, whereas polyamines may
      promote the growth of tumor cells. Both the tumoricidal and growth-promoting
      activities from macrophages have been reported; however, the underlying
      mechanisms for switching between this dual function of macrophages remain
      unclear. Here, we test the hypothesis that arginase participates in the switching
      between the cytotoxic and growth-promoting activities of macrophages toward tumor
      cells. To alter arginase activity in macrophages, cells (murine macrophage cell
      line J774A.1) were transfected with the rat liver arginase gene or treated with
      an arginase inhibitor, L-norvaline. The effects of macrophage arginase activity
      on the growth-promoting and cytotoxic activities of macrophages toward breast
      tumor cells (ZR-75-1) were investigated in a coculture system. The results
      demonstrated that overexpression of arginase in macrophages enhanced L-ornithine
      and putrescine production and consequently promoted tumor cell proliferation.
      This proliferative effect was down-regulated by the arginase inhibitor L
      norvaline. Furthermore, increases in arginase activity also attenuated NO
      production by the lipopolysaccharide-activated macrophages and thus reduced the
      cytotoxic effect on cocultured tumor cells. Inhibiting arginase activity by L
      norvaline effectively reversed the suppression of NO-mediated tumor cytotoxicity.
      Together, these results suggest that arginase induction in macrophages can
      enhance tumor cell growth by providing them with polyamines and suppress tumor
      cytotoxicity by reducing NO production. It appears that L-arginine metabolism
      through the arginase and iNOS pathways in macrophages can have very different
      influences on the growth of nearby tumor cells depending on which pathway is
      prevailing.

PMID- 11221840
TI  - Optimal induction of effector but not memory antitumor cytotoxic T lymphocytes
      involves direct antigen presentation by the tumor cells.
AB  - MHC class I-restricted tumor antigen can be presented to CD8+ T cells by two
      distinct mechanisms. Direct presentation involves degradation of cytosolic
      proteins by the proteosome into peptides, transport of the peptides across the
      endoplasmic reticulum membrane, and expression of the MHC-peptide complex on the
      tumor cell surface. Cross-presentation, on the other hand, involves uptake and
      intracellular processing of the tumor antigen by host antigen-presenting cells.
      Whereas it is clear that cross-presentation is necessary and sufficient for the
      induction of memory CTLs, it has not been tested whether such presentation is
      sufficient to induce effector CTLs. Here we analyzed the requirements of direct
      antigen presentation for the induction of effector and memory antitumor CTLs
      using a MHC class I- mutant incapable of direct antigen presentation and its
      parent, the MHC class I+ J558 cell line. We report that in comparison with the
      MHC class I+ tumor cell, the MHC class I- mutant induces equal priming for recall
      CTL response but poor effector CTLs. Our results demonstrate that optimal
      induction of effector CTLs, but not memory CTLs, requires direct antigen
      presentation by the tumor cells.

PMID- 11221841
TI  - Heat-activated transgene expression from adenovirus vectors infected into human
      prostate cancer cells.
AB  - Replication-deficient adenovirus expression vectors were used to introduce a
      recombinant DNA construct containing enhanced green fluorescent protein (EGFP)
      under control of a truncated, human heat shock promoter into human prostate
      cancer cells growing either exponentially or in plateau phase. This was done to
      measure controlled, heat shock-induced EGFP expression under conditions relevant
      to treating human cancers with heat-activated gene therapy. Both the temporal
      duration and magnitude of EGFP expression increased proportionately with stronger
      heat shocks (time at temperature) up to maximum values that were induced by 4 h
      at 41.0 degrees C or 2 h at 42.0 degrees C. Longer heat shocks at either
      temperature yielded no additional EGFP expression and ultimately reduced it.
      Maximal EGFP expression was induced in exponential cultures by heat shocks
      delivered 12-24 h after virus infection. Induction at progressively later
      postinfection times induced increasingly lower, peak EGFP expression. Maximal
      EGFP expression could not be induced until 48 h after infection of plateau phase
      cultures but could still be induced 180 h after virus infection. However, peak
      EGFP levels in plateau cultures were approximately 25-50% of those observed in
      identically induced exponential cultures. Ostensibly, the differences in
      expression from the heat shock promoter observed in exponential and plateau
      cultures were attributable to cell division diluting the vector within
      exponential cultures and the lower metabolic activity in serum-starved plateau
      cultures. For all experimental conditions, EGFP expression induced from the heat
      shock promoter was comparable with or higher than that from the constitutively
      active cytomegalovirus promoter over any 24-h period. The experimental results
      demonstrated that EGFP expression from the heat shock promoter was controllable
      in both exponential and plateau phase cultures and support the plausibility of
      using controlled heat shock activation of this promoter as a means of regulating
      both the spatial and temporal expression of therapeutic DNA constructs within
      human tissues. The ability to localize and regulate expression from the heat
      shock promoter may prove particularly advantageous for many cancer applications,
      especially if the therapeutic products are highly toxic, e.g., proteotoxins or
      cytokines. However, the results of this study suggest that differential growth
      conditions within tumors could markedly affect the expression of recombinant DNA
      under control of both inducible and constitutive promoters. Consequently,
      inducing schemes may need to be spatially adjusted to obtain the desired
      therapeutic results in all tumor domains using heat-activated gene therapy.

PMID- 11221842
TI  - Analysis of complex relationships between age, p53, epidermal growth factor
      receptor, and survival in glioblastoma patients.
AB  - Glioblastoma multiforme (GBM) carries a dismal prognosis. However, a range of
      survival times exists, and parameters that define prognostic groups may help to
      optimize treatment. To identify such prognostic groups, we analyzed tumor tissue
      from 110 cases of newly diagnosed GBM from two clinical protocols. Similar to
      other studies, we found no association of epidermal growth factor receptor (EGFR)
      overexpression (as assessed by immunohistochemistry), p53 immunopositivity, or
      p53 mutation with survival in the entire sample. However, EGFR overexpression
      showed trends toward worse prognosis in patients younger than the median age, but
      better prognosis in patients older than the median age. This interaction of EGFR
      with age group was statistically significant and led us to focus our further
      analyses on the younger patients. In this group, a statistically significant
      association of EGFR overexpression with worse survival was identified in the p53
      negative but not p53-positive tumors. We found a similar result after screening
      these cases for mutations in p53: EGFR overexpression was negatively associated
      with survival only in the p53 wild-type cases. To confirm this unexpected result,
      this finding was reproduced in a validation sample of an additional 42 tumors
      from younger patients on the same two clinical protocols. This complex
      relationship between EGFR and p53 in younger patients remained in a multivariate
      analysis that incorporated additional prognostic variables. The results suggest
      that analysis of prognostic markers in GBM is complex, and maximal information
      may require analysis of subgroups based on age and the status of specific markers
      such as p53. In addition, they suggest a specific group of patients on which to
      focus promising therapies targeting EGFR.

PMID- 11221843
TI  - Different mechanisms of radiation-induced loss of heterozygosity in two human
      lymphoid cell lines from a single donor.
AB  - Allelic loss is an important mutational mechanism in human carcinogenesis. Loss
      of heterozygosity (LOH) at an autosomal locus is one outcome of the repair of DNA
      double-strand breaks (DSBs) and can occur by deletion or by mitotic
      recombination. We report that mitotic recombination between homologous
      chromosomes occurred in human lymphoid cells exposed to densely ionizing
      radiation. We used cells derived from the same donor that express either normal
      TP53 (TK6 cells) or homozygous mutant TP53 (WTK1 cells) to assess the influence
      of TP53 on radiation-induced mutagenesis. Expression of mutant TP53 (Met 237 Ile)
      was associated with a small increase in mutation frequencies at the hemizygous
      HPRT (hypoxanthine phosphoribosyl transferase) locus, but the mutation spectra
      were unaffected at this locus. In contrast, WTK1 cells (mutant TP53) were 30-fold
      more susceptible than TK6 cells (wild-type TP53) to radiation-induced mutagenesis
      at the TK1 (thymidine kinase) locus. Gene dosage analysis combined with
      microsatellite marker analysis showed that the increase in TK1 mutagenesis in
      WTK1 cells could be attributed, in part, to mitotic recombination. The
      microsatellite marker analysis over a 64-cM region on chromosome 17q indicated
      that the recombinational events could initiate at different positions between the
      TK1 locus and the centromere. Virtually all of the recombinational LOH events
      extended beyond the TK1 locus to the most telomeric marker. In general, longer
      LOH tracts were observed in mutants from WTK1 cells than in mutants from TK6
      cells. Taken together, the results demonstrate that the incidence of radi-ation
      induced mutations is dependent on the genetic background of the cell at risk, on
      the locus examined, and on the mechanisms for mutation available at the locus of
      interest.

PMID- 11221844
TI  - Signaling events triggered by tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL): caspase-8 is required for TRAIL-induced apoptosis.
AB  - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a TNF
      family member and potent apoptosis inducer. In contrast to TNF-alpha or Fas
      ligand, relatively little is known about the signaling events activated by TRAIL.
      In particular, the initial caspase(s) required for TRAIL-induced apoptosis
      remains to be determined Caspase-3-like protease but not caspase-1-like protease
      (YVADase) activity rapidly increased in HeLa cells in response to TRAIL
      treatment. The increase in protease activity correlated with the profile of
      apoptotic cell death that was inhibited by the pan-caspase inhibitor Z-VAD-fmk.
      In response to TRAIL, caspase-8, an initiator caspase in death receptor-mediated
      apoptosis, was activated within 1 h in association with Bid cleavage, cytochrome
      c release, caspase-3 activation, and DNA fragmentation factor 45 cleavage. Z-IETD
      fmk, a caspase-8 inhibitor, completely blocked caspase-8 activation and resulted
      in inhibition of caspase-3 (a caspase-3-like protease) activation and apoptotic
      cell death. Overexpression of a caspase-8 dominant negative mutant inhibited
      apoptosis induced by TRAIL. Caspase-8-deficient Jurkat cells were resistant to
      both TRAIL and Fas-induced apoptosis, whereas wild-type Jurkat cells were
      susceptible to both TRAIL- and Fas-induced apoptosis. The caspase-8-reintro duced
      caspase-8-deficient Jurkat cells acquired normal susceptibility to both TRAIL and
      agonistic Fas antibody. Reverse transcription-PCR and sequence analyses have
      revealed that these caspase-8-deficient Jurkat cell express wild-type caspase-10.
      Therefore, our data indicate that caspase-8 is required for TRAIL-induced
      apoptosis and suggest that caspase-10 may play a minor role, if any, in TRAIL
      induced apoptosis.

PMID- 11221845
TI  - Identification of a novel member of the snail/Gfi-1 repressor family, mlt 1,
      which is methylated and silenced in liver tumors of SV40 T antigen transgenic
      mice.
AB  - DNA methylation is the only known mechanism for an epigenetic genomic DNA
      modification that is capable of altering gene expression. A recent study reveals
      that the pattern of CpG island methylation is largely characteristic of tumor
      type, suggesting that distinct sets of genes are inactivated by methylation
      during development of each tumor type. We compared previously the methylation
      status between normal liver and liver tumors in SV40 T/t antigen transgenic mice
      (MT-D2 mice) using Restriction Landmark Genomic Scanning for Methylation (RLGS-M)
      and identified several loci/spots that appeared to be methylated frequently in
      liver tumors. One of these spots, B236, identified a locus on chromosome 12
      (D12Ncvs7) syntenic with human 14q12-q21 that is frequently lost in certain human
      cancers. Shotgun sequencing of a bacterial artificial chro mosome clone
      containing this spot/locus was performed to identify genes within this region.
      The Genescan program predicted an open reading frame of a novel, intron-less gene
      adjacent to the B236 spot that encodes a putative 493-amino acid protein
      containing the SNAG repressor motif in the NH2-terminal region and five C2H2-type
      zinc finger motifs in the COOH-terminal half. This putative gene, methylated in
      liver tumor (mlt 1), is a novel member of the SNAG transcriptional repressor
      family with 43% amino acid identity to insulinoma-associated protein 1. An open
      reading frame encoding a protein quite similar to mouse mlt 1 (56% amino acid
      identity) was located in the syntenic region of the human genome, indi cating
      that mlt 1 is evolutionarily conserved in human. Northern blot analysis revealed
      that mlt 1 is normally expressed in brain, spleen, stom ach, and liver. However,
      mlt 1 expression was silenced in the liver tumors of MT-D2 mice. The putative
      promoter region of mlt 1 is unmethylated in normal tissues but methylated in all
      liver tumors from 11 MT-D2 mice We also found that mlt 1 was methylated and not
      expressed in N18TG-22 cells, a mouse neuroblastoma cell line. Treatment of N18TG
      2 cells with a demethylating agent, 5-aza-deoxycytidine, resulted in an
      expression of mlt 1, indicating that the repression of mlt 1 is attributable to
      methylation Thus, mlt 1 is a novel target gene that is silenced by methylation
      during liver tumorigenesis initiated by SV40 T antigen.

PMID- 11221846
TI  - Evidence for three tumor suppressor loci on chromosome 9p involved in melanoma
      development.
AB  - Cytogenetic and loss of heterozygosity (LOH) studies have long indicated the
      presence of a tumor suppressor gene (TSG) on 9p involved in the development of
      melanoma. Although LOH at 9p has been reported in approximately 60% of melanoma
      tumors, only 5-10% of these tumors have been shown to carry CDKN2A mutations,
      raising the possibility that another TSG involved in melanoma maps to chromosome
      9p. To investigate this possibility, a panel of 37 melanomas derived from 35
      individuals was analyzed for CDKN2A mutations by single-strand conformation
      polymorphism analysis and sequencing. The melanoma samples were then typed for 15
      markers that map to 9p13-24 to investigate LOH trends in this region. In those
      tumors demonstrating retention of heterozygosity at markers flanking CDKN2A and
      LOH on one or both sides of the gene, multiplex microsatellite PCR was performed
      to rule out homozygous deletion of the region encompassing CDKN2A. CDKN2A
      mutations were found in tumors from 5 patients [5 (14%) of 35], 4 of which
      demonstrated LOH across the entire region examined. The remaining tumor with no
      observed LOH carried two point mutations, one on each allele. Although LOH was
      identified at one or more markers in 22 (59%) of 37 melanoma tumors corresponding
      to 20 (57%) of 35 individuals, only 11 tumors from 9 individuals [9 (26%) of 35]
      demonstrated LOH at D9S942 and D9S1748 the markers closest to CDKN2A. Of the
      remaining 11 tumors with LOH 9 demonstrated LOH at two or more contiguous markers
      either centromeric and/or telomeric to CDKN2A while retaining heterozygosity at
      several markers adjacent to CDKN2A. Multiplex PCR revealed one tumor carried a
      homozygous deletion extending from D9S1748 to the IFN-alpha locus. In the
      remaining eight tumors, multiplex PCR demonstrated that the observed
      heterozygosity was not attributable to homozygous deletion and stromal
      contamination at D9S1748, D9S942, or D9S974, as measured by comparative
      amplification strengths, which indicates that retention of heterozygosity with
      flanking LOH does not always indicate a homozygous deletion. This report supports
      the conclusions of previous studies that a least two TSGs involved in melanoma
      development in addition to CDKN2A may reside on chromosome 9p.

PMID- 11221847
TI  - Induction and intracellular regulation of tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL) mediated apotosis in human malignant glioma cells.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) preferentially
      triggers apoptosis in tumor cells versus normal cells, thus providing a
      therapeutic potential. In this study, we examined a large panel of human
      malignant glioma cell lines and primary cultures of normal human astrocytes for
      their sensitivity to TRAIL. Of 13 glioma cell lines, 3 were sensitive (80-100%
      death), 4 were partially resistant (30-79% death), and 6 were resistant (< 30%
      death). Normal astrocytes were also resistant. TRAIL-induced cell death was
      characterized by activation of caspase-8 and -3, poly(ADP-ribose) polymerase
      cleavage, and DNA fragmentation. Decoy receptor (DcR1 and DcR2) expression was
      limited in the glioma cell lines and did not correlate with TRAIL sensitivity.
      Both sensitive and resistant cell lines expressed TRAIL death receptor (DR5),
      adapter protein Fas-associated death domain (FADD), and caspase-8; but resistant
      cell lines expressed 2-fold higher levels of the apoptosis inhibitor
      phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes-15 kDa
      (PED/PEA-15). In contrast, cellular FADD-like IL-1beta-converting enzyme-like
      inhibitory protein (cFLIP) expression was similar in sensitive and resistant
      cells. Transfection of sense PED/PEA-15 cDNA in sensitive cells resulted in cell
      resistance, whereas transfection of antisense in resistant cells rendered them
      sensitive. Inhibition of protein kinase C (PKC) activity restored TRAIL
      sensitivity in resistant cells, suggesting that PED/ PEA-15 function might be
      dependent on PKC-mediated phosphorylation. In summary, TRAIL induces apoptosis in
      > 50% of glioma cell lines, and this killing occurs through activation of the DR
      pathway. This caspase-8-induced apoptotic cascade is regulated by intracellular
      PED/PEA-15, but not by cFLIP or decoy receptors. This pathway may be exploitable
      for glioma and possibly for other cancer therapies.

PMID- 11221848
TI  - Loss of heterozygosity mapping at chromosome arm 16q in 712 breast tumors reveals
      factors that influence delineation of candidate regions.
AB  - Loss of heterozygosity (LOH) at the long arm of chromosome 16 occurs in at least
      half of all breast tumors and is considered to target one or more tumor
      suppressor genes. Despite extensive studies by us and by others, a clear
      consensus of the boundaries of the smallest region of overlap (SRO) could not be
      identified. To find more solid evidence for SROs, we tested a large series of 712
      breast tumors for LOH at 16q using a dense map of polymorphic markers. Strict
      criteria for LOH and retention were applied, and results that did not meet these
      criteria were excluded from the analysis. We compared LOH results obtained from
      samples with different DNA isolation methods, ie., from microdissected tissue
      versus total tissue blocks. In the latter group, 16% of the cases were excluded
      because of noninterpretable LOH results. The selection of polymorphic markers is
      clearly influencing the LOH pattern because a chromosomal region seems more
      frequently involved in LOH when many markers from this region are used. The LOH
      detection method, i.e., radioactive versus fluorescence detection, has no marked
      effect on the results. Increasing the threshold window for retention of
      heterozygosity resulted in significantly more cases with complex LOH, i.e.,
      several alternating regions of loss and retention, than seen in tumors with a
      small window for retention. Tumors with complex LOH do not provide evidence for
      clear-cut SROs that are repeatedly found in other samples. On disregarding these
      complex cases, we could identify three different SROs, two at band 16q24.3 and
      one at 16q22.1. In all three tumor series, we found cases with single LOH regions
      that designated the distal region at 16q24.3 and the region at 16q22.1. Comparing
      histological data on these tumors did not result in the identification of a
      particular subtype with LOH at 16q or a specific region involved in LOH. Only the
      rare mucinous tumors had no 16q LOH at all. Furthermore, a positive estrogen
      content is prevalent in tumors with 16q LOH, but not in tumors with LOH at
      16q24.3 only.

PMID- 11221849
TI  - A modest reduction in c-myc expression has minimal effects on cell growth and
      apoptosis but dramatically reduces susceptibility to Ras and Raf transformation.
AB  - Dergulation of c-myc and mutation of ras genes is commonly found in many human
      tumors. Several lines of evidence indicate that c-Myc and oncogenic Ras cooperate
      in causing malignant transformation, but the mechanism of this cooperation is not
      understood. We set out to investigate the effect on transformation of a modest
      reduction in endogenous c-Myc expression, which was achieved using a c-myc
      heterozygous cell line constructed by targeted homologous recombination. In
      contrast to previous reports where c-Myc expression or activity was ablated using
      antisense or dominant-defective methods, use of c-myc +/- cells provides a stable
      and homogeneous cell culture system with a precisely defined c-Myc expression
      level. In addition, this approach does not suffer from nonspecific artifacts such
      as antisense oligonucleotide toxicity or interference of dominant-defective
      proteins with multiple (and often undefined) target proteins. The striking and
      unexpected finding communicated here is that the relatively modest 50% reduction
      in c-Myc expression resulted in a greater than 10-fold reduction in
      susceptibility to transformation by oncogenic Ras or Raf proteins. This very
      significant defect in transformation potential cannot be explained on the basis
      of a generalized cell-cycle defect, because c-myc +/- cells exhibit only a
      minimal (20%) reduction in proliferation. Genetic epistasis analysis indicated
      that c-Myc and Ras acted by independent pathways that converged to regulate the
      abundance of the cyclin-dependent kinase inhibitor protein p27Kip1. Anchorage
      deprivation elicited a strong up-regulation of p27, and a 50% reduction in c-Myc
      expression significantly compromised the ability of Ras to down-regulate p27. We
      propose that Ras and c-Myc signals cooperate to regulate the activity of cyclin D
      Cdk4/6 complexes: the former by up-regulating the expression of cyclin D1 and the
      latter by affecting the activity of the complexes. Ectopic expression of cyclin A
      restored the transformation potential of c-myc +/- cells, implicating it as a
      downstream genetic component in the pathway. From a therapeutic standpoint, it is
      of interest that, although transformation appears to be very sensitive to c-Myc
      expression levels, much larger reductions can be tolerated without causing any
      significant cell cycle defects.

PMID- 11221850
TI  - Involvement of the Oct-1 regulatory element of the gadd45 promoter in the p53
      independent response to ultraviolet irradiation.
AB  - The gadd45 gene, a growth arrest and DNA damage (gadd)-induced gene, is
      transcriptionally activated by UV irradiation through two distinct pathways. One
      requires the sequence-specific binding of the p53 tumor suppressor protein to a
      responsive element within the third intron of the gadd45 gene, and the other is
      p53-independent activation of the gadd45 promoter region, although the UV
      response element that mediates this has yet to be defined. To investigate the
      sequences involved in induction of gadd45 by UV irradiation in a p53-independent
      pathway, we performed mutation analyses of the human gadd45 promoter fused to the
      luciferase reporter gene in cell lines in which p53 was inactivated. We found
      that the UV-responsive element was involved in the Oct-1 binding site at -99 bp
      relative to the transcription start site. Electrophoretic mobility shift assays
      showed that Oct-1, a transcription factor, bound this element on the gadd45 gene,
      although the intensity and mobility pattern of the retarded bands were not
      altered by UV irradiation. These results suggest that the Oct-1 regulatory
      element might be one of the essential elements involved in the activation of the
      gadd45 promoter by UV irradiation in a p53-independent pathway.

PMID- 11221851
TI  - Expression of adrenomedullin and peptide amidation activity in human prostate
      cancer and in human prostate cancer cell lines.
AB  - After therapeutic hormone deprivation, prostate cancer (CaP) cells often develop
      androgen-independent growth through not-well-defined mechanisms. The presence of
      neuroendocrine (NE) cells is often greater in prostate carcinoma than in normal
      prostate, and the frequency of NE cells correlates with tumor malignancy, loss of
      androgen sensitivity, increase of autocrine-paracrine activity, and poor
      prognosis. In some CaPs, neuropeptides have been previously implicated as growth
      factors. Peptidylglycine alpha-amidating monooxygenase (PAM) is the enzyme
      producing alpha-amidated bioactive peptides from their inactive glycine-extended
      precursors. In the present work, we demonstrate that androgen-independent PC-3
      and DU145 cell lines, derived from human CaP, express PAM in vitro and in
      xenografts implanted in athymic nude mice, indicating that they are able to
      produce alpha-amidated peptides. Contrarily, barely detectable levels of PAM were
      found in the androgen-sensitive LNCaP cell line. We also show that whereas PC-3
      and DU145 cells produce and secrete adrenomedullin (AM), a multifunctional
      amidated peptide, no expression was found in LNCaP cells. We further demonstrate
      that AM acts as a growth factor for DU145 cells, which suggests the existence of
      an autocrine loop mechanism that could potentially drive neoplastic growth. PAM
      mRNA levels were found to be 3-fold higher in prostate adenocarcinomas compared
      with that of human benign prostate hyperplasia (BPH) as demonstrated by real-time
      quantitative reverse transcription-PCR. The analysis of AM message expression in
      BPH and CaP (Gleason's score, 6-9) shows a clear distinction between benign and
      CaP. The expression was detected only in adenocarcinomas tissues with a marked
      increase in samples with a high Gleason's score. Immunocytochemically, AM was
      localized in the carcinomatous epithelial compartment. NE phenotype, assessed
      after the immunocytochemical localization of neuron-specific enolase (NSE), was
      found in both the epithelial and the stromal compartments of cancers; in BPH,
      only some spare basal cells were NSE-labeled. Cancer progression could be
      accelerated by peptides secreted by a population of cells capable of inducing
      androgen-independent tumoral growth via autocrine-paracrine mechanisms.

PMID- 11221852
TI  - Involvement of Flt-1 tyrosine kinase (vascular endothelial growth factor receptor
      1) in pathological angiogenesis.
AB  - Vascular endothelial growth factor (VEGF) and its two receptors, Fms-like
      tyrosine kinase 1 (Flt-1) (VEGFR-1) and KDR/Flk-1 (VEGFR-2), have been
      demonstrated to be an essential regulatory system for blood vessel formation in
      mammals. KDR is a major positive signal transducer for angiogenesis through its
      strong tyrosine kinase activity. Flt-1 has a unique biochemical activity, 10-fold
      higher affinity to VEGF, whereas much weaker tyrosine kinase activity compared
      with KDR. Recently, we and others have shown that Flt-1 has a negative regulatory
      function for physiological angiogenesis in the embryo, possibly with its strong
      VEGF-trapping activity. However, it is still open to question whether the
      tyrosine kinase of Flt-1 has any positive role in angiogenesis at adult stages.
      In this study, we examined whether Flt-1+ could be a positive signal transducer
      under certain pathological conditions, such as angiogenesis with tumors
      overexpressing a Flt-1-specific, VEGF-related ligand. Our results show clearly
      that murine Lewis lung carcinoma cells overexpressing placenta growth factor-2,
      an Flt-1-specific ligand, grew in wild-type mice much faster than in Flt-1
      tyrosine kinase domain-deficient mice. Blood vessel formation in tumor tissue was
      higher in wild-type mice than in Flt-1 tyrosine kinase-deficient mice. On the
      other hand, the same carcinoma cells overexpressing VEGF showed no clear
      difference in the tumor growth rate between these two genotypes of mice. These
      results indicate that Flt-1 is a positive regulator using its tyrosine kinase
      under pathological conditions when the Flt-1-specific ligand is abnormally highly
      expressed. Thus, Flt-1 has a dual function in angiogenesis, acting in a positive
      or negative manner in different biological conditions.

PMID- 11221853
TI  - Chromosomal rearrangements and oncogene amplification precede aneuploidization in
      the genetic evolution of breast cancer.
AB  - Breast carcinoma is thought to arise because of multiple successive changes in
      the genome of the normal epithelial cells. However, little is known of the order
      of appearance of different types of genetic aberrations We studied the ERBB2 (Her
      2/neu) and CCND1 (cyclin D1) oncogene amplification in flow cytometrically sorted
      diploid and nondiploid tumor cell populations by fluorescence in situ
      hybridization (FISH). The purity of the cell sorting was confirmed by static DNA
      image cytometry. Spectral karyotyping was used to define differences in a genome
      wide manner between two distinctly different aneuploid cell clones found in each
      of two breast cancer cell lines. FISH indicated the presence of gene
      amplification both in diploid and nondiploid cell clones in 17 of the 21
      amplification-containing tumors analyzed. The oncogene copy numbers remained
      unchanged throughout aneuploidization in 11 of 17 tumors. The remaining six
      tumors showed an increase in oncogene copy number as well as the number of
      chromosome 11 or 17 centromeres (the original location of CCNDI and ERBB2,
      respectively). Breast carcinoma cell lines MDA-157 and MDA-436 showed a
      significant number of chromosomal rearrangements in the near-diploid clones,
      which were present in duplicate in the corresponding aneuploid (polyploid)
      clones. These results indicate that ploidy shift, ie., aneuploidization, in
      breast cancer is a late genetic event which is preceded by both oncogene
      amplifications as well as many chromosomal rearrangements.

PMID- 11221854
TI  - Intranuclear compartmentalization of cyclin E during the cell cycle: disruption
      of the nucleoplasm-nucleolar shuttling of cyclin E in bladder cancer.
AB  - Cyclin E/cyclin-dependent kinase 2 complexes are essential during the cell cycle
      for entrance into S phase. Cyclin E expression starts in mid-G1, reaches a
      maximum at S-phase entrance, and undergoes proteolysis mediated by the ubiquitin
      pathway as the cell progresses through S phase. Laser scanning cytometry, a
      microscope-based cytofluorometer combining the advantages of both flow and image
      analysis, allowed the determination of subcellular localization of cyclin E, p27,
      and retinoblastoma protein during cell cycle progression in normal human
      fibroblasts and nine bladder cancer cell lines. We observed that in normal
      fibroblasts and most tumor cell lines, cyclin E localizes in the nucleoplasm
      during mid-G1, and is translocated to the nucleolus during G1-S-phase transition,
      and its levels are undetectable in G2-M phase. Neither levels nor subcellular
      localization of p27 and retinoblastoma protein was cell cycle dependent in normal
      or tumor cells. However, four of nine bladder cancer cell lines continued to
      express cyclin E in all phases of the cycle, and image analysis revealed that it
      was localized to nucleoli. These observations suggest that the nucleolus mediates
      a cyclin E "shuttling" between the nucleus and the cytoplasm that is probably
      involved in its regulation and that this mechanism could be disrupted in bladder
      cancer.

PMID- 11221855
TI  - Loss of caspase-1 and caspase-3 protein expression in human prostate cancer.
AB  - Activation of the caspase cascade is involved in the execution of apoptosis in a
      variety of cellular systems. Recent studies demonstrated that caspase-1
      activation was required for human prostate cancer cells to undergo apoptosis in
      response to transforming growth factor-beta (Y. Guo and N. Kyprianou, Cancer
      Res., 59: 1366-1371, 1999). In the present study, to identify the significance of
      caspases in prostate cancer progression, we examined the expression of three key
      caspases, caspase-1, caspase-3, and caspase-9, in normal and malignant human
      prostates. Caspase-1, -3, and -9 expression was examined at the mRNA and the
      protein level in a series of human normal and malignant prostate specimens. No
      significant differences were observed in the mRNA expression in prostatic tumors
      relative to the normal gland for any of the three caspases. Immunohistochemical
      analysis revealed that the pattern of protein expression and distribution was
      uniformly homogeneous in the normal prostate, with the epithelial cells
      exhibiting a diffuse cytoplasmic staining for caspase-1 and caspase-3.
      Significantly, the majority of primary prostate cancer specimens (80%) had total
      lack of caspase-1 immunoreactivity, whereas the remaining showed a significantly
      reduced expression compared with the normal prostate (P < 0.05). Caspase-3
      expression was also reduced in moderately and poorly differentiated prostatic
      tumors compared with well-differentiated prostate adenocarcinomas and the normal
      prostate (P < 0.05). No significant correlation was found between the apoptotic
      index or Gleason grade and the pattern of caspase protein expression in the
      primary prostatic tumors analyzed. Western blot analysis revealed constitutive
      expression of the proenzyme forms of caspase-1, -3, and -9 in the human prostate
      cancer cell lines PC-3, DU-145, TSU-Pr1m and LNCaP, but caspase-1 expression was
      low in the less tumorigenic cell lines, DU-145 and LNCaP. These findings
      implicate the loss of caspase-1 protein as a potential step in the loss of
      apoptotic control during prostate tumorigenesis. This study suggests that the
      pattern of caspase-1 and -3 expression in prostatic tumors may have prognostic
      significance in disease progression.

PMID- 11221856
TI  - Induction of apoptotic cell death and prevention of tumor growth by ceramide
      analogues in metastatic human colon cancer.
AB  - Dysfunction in the physiological pathways of programmed cell death may promote
      proliferation of malignant cells, and correction of such defects may selectively
      induce apoptosis in cancer cells. We measured the levels of ceramide, a candidate
      lipid mediator of apoptosis, in human metastatic colorectal cancer and tested in
      vitro and in vivo effects of various ceramide analogues in inducing apoptosis in
      metastatic colon cancer. Human colon cancer showed a > 50% decrease in the
      cellular content of ceramide when compared with normal colon mucosa. Application
      of ceramide analogues and ceramidase inhibitors induced rapid cell death through
      activation of various proapoptotic molecules, such as caspases and release of
      cytochrome c. Ceramidase inhibition increases the ceramide content of tumor
      cells, resulting in maximum activation of the apoptotic cascade. Normal liver
      cells were completely resistant to inhibitors of ceramidases. Treatment of nude
      mice with B13, the most potent ceramidase inhibitor, completely prevented tumor
      growth using two different aggressive human colon cancer cell lines metastatic to
      the liver. Therefore, B13 and related analogues of ceramide and inhibitors of
      ceramidases offer a promising therapeutic strategy with selective toxicity toward
      malignant but not normal cells. These studies also suggest that the ceramide
      content in cancer cells might be involved in the pathogenesis of tumor growth in
      vitro and in vivo.

PMID- 11221857
TI  - Tumor hypoxia, the physiological link between Trousseau's syndrome (carcinoma
      induced coagulopathy) and metastasis.

PMID- 11221858
TI  - Selected cell and selective microenvironment in neoplastic development.
AB  - Recent analysis of genetic alterations in human cancer points to a major role for
      selection in neoplastic development but provides few details about the dynamics
      of the process. Many such details, however, have emerged from quantitative
      studies of spontaneous transformation among mammalian cells in culture. The chief
      insight of these studies is that there is a continuous generation of variants in
      proliferative potential among growing cells that provides the substratum for
      progressive development to a frankly neoplastic state when selective growth
      conditions are persistently applied. Much of the selection occurs before the
      cells are capable of producing discrete neoplastic foci. The varied observations
      in cell culture draw attention to analogous features of carcinogenesis in
      experimental animals and the development of human cancer.

PMID- 11221859
TI  - Protein kinase C-epsilon transgenic mice: a unique model for metastatic squamous
      cell carcinoma.
AB  - Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are the most common
      forms of human skin cancer. BCC is slow growing and mostly localized, whereas SCC
      metastasizes to the regional lymph nodes and subsequently to distal organs. In
      murine skin carcinogenesis models for SCC, the incidence of metastasis is very
      low. We report here that FVB/N transgenic mice, which overexpress (approximately
      18-fold) epitope-tagged protein kinase C-epsilon (T7-PKCepsilon) protein in the
      epidermis provide a unique murine model system for highly malignant/metastatic
      SCC. Skin tumors were developed by the initiation-promotion protocol (initiation
      with 100 nmol 7,12-dimethyl-benz[a]anthracene; promotion with 5 nmol 12-O
      tetradecanoylphorbol-13-acetate twice weekly). T7-PKCepsilon transgenic mice
      showed 92% suppression of papilloma development compared with wild-type
      littermates after 23 weeks of tumor promotion. However, within 15-20 weeks of 12
      O-tetradecanoylphorbol-13-acetate promotion, 40% of T7-PKCepsilon mice developed
      at least one carcinoma compared with 7% of the wild-type mice. All carcinomas
      from T7-PKCepsilon mice appeared without prior papilloma formation.
      Interestingly, 7,12-dimethyl-benz[a]anthracene alone resulted in the development
      of squamous cell carcinomas in 22% of T7-PKCepsilon mice, whereas wild-type
      littermates developed no tumors. Histopathological analysis of tumors from
      multiple T7-PKCepsilon mice revealed moderately differentiated SCC invading the
      dermal region with neoplasia appearing to originate and invade from the hair
      follicle. Carcinomas of T7-PKCepsilon mice rapidly metastasized to regional lymph
      nodes within 3 weeks of appearance. In wild-type mice, the grade of the invading
      tumors, originating from interfollicular epidermis, was pathologically
      categorized as well-differentiated SCC and remained localized to the dermis. The
      T7-PKCepsilon transgenic mice may provide a rapid and unique in vivo model to
      investigate metastatic SCC.

PMID- 11221860
TI  - Efficient oncolysis by a replicating adenovirus (ad) in vivo is critically
      dependent on tumor expression of primary ad receptors.
AB  - Replicating adenoviruses (Ads) are designed to replicate in and destroy cancer
      cells, generating viral progeny that spread within the tumor. To address the
      importance of the primary cellular receptor for Ads, the coxsackievirus and Ad
      receptor (CAR), in permitting intratumoral spread of a replicating Ad, we have
      used a pair of tumor cell lines differing only in the expression of a primary
      receptor for Ad5. This novel system thus allowed the first direct evaluation of
      the relationship between the efficacy of a replicating Ad and the primary
      receptor levels of the host cell without the confounding influence of other
      variable cellular factors. We demonstrate that the absence of the primary
      cellular receptor on the tumor cells restricts the oncolytic potency of a
      replicating Ad both in vitro and in vivo. Based on these findings, it is apparent
      that the potential therapeutic advantages afforded by viral replication would be
      negated by poor intratumoral spread of the viral progeny due to the failure to
      infect neighboring tumor cells. Because a number of studies have reported that
      primary cancer cells express only low levels of CAR, our results suggest that
      strategies to redirect Ads to achieve CAR-independent infection will be necessary
      to realize the full potential of replicating Ads in the clinical setting.

PMID- 11221861
TI  - Evidence that genetic instability occurs at an early stage of colorectal
      tumorigenesis.
AB  - Chromosomal instability is believed to be a common feature of most human tumors,
      but the stage at which such instability originates has not been defined. At the
      molecular level, chromosomal instability is characterized by allelic imbalance
      (AI), representing losses or gains of defined chromosomal regions. We have
      assessed AI in early colorectal tumors using newly developed methods for
      assessing AI in complex cell populations. A total of 32 adenomas of average size
      (2 mm; range, 1-3 mm) were studied. AI of chromosome 5q markers occurred in 55%
      of tumors analyzed, consistent with a gatekeeping role of the adenomatous
      polyposis coli tumor suppressor gene located at chromosomal position 5q21. AI was
      also detected in each of the other four chromosomes tested. The fractions of
      adenomas with AI of chromosomes 1p, 8p, 15q, and 18q were 10,19, 28, and 28%,
      respectively. Over 90% of the tumors exhibited AI of at least one chromosome, and
      67% had allelic imbalance of a chromosome other than 5q. These findings
      demonstrate that AI is a common event, even in very small tumors, and suggest
      that chromosomal instability occurs very early during colorectal neoplasia.

PMID- 11221862
TI  - PAX3 is expressed in human melanomas and contributes to tumor cell survival.
AB  - Deregulated expression of the transcription factor PAX3 was observed previously
      in several tumors like rhabdomyosarcoma and Ewing's sarcoma. Because PAX3
      expression is also found in pluripotent neural crest cells, we investigated
      whether melanomas, tumors derived mostly from cutaneous intraepidermal
      melanocytes, might show deregulated PAX3 expression. Using a specific and
      sensitive reverse transcription-PCR, we detected PAX3 mRNA in 77% (27 of 35) of
      primary cultured melanomas. These results could be confirmed by direct in situ
      hybridization on the corresponding tissue sections where PAX3 expression was
      unambiguously confined to tumor cells and not detected in surrounding normal
      tissue, normal skin sections, or sections of benign lesions. Furthermore, down
      regulation of PAX3 expression achieved through a specific antisense
      oligonucleotide-based treatment resulted in > 70% of dead cells specifically in
      PAX3-positive melanomas. Annexin V staining confirmed that primary melanoma cells
      underwent apoptosis after treatment These experiments suggest that in situ
      hybridization of PAX3 on paraffin-embedded tissue may represent a novel means to
      identify melanoma cell lesions, which appear to become dependent on expression of
      this deregulated transcription factor.

PMID- 11221863
TI  - Methylation of O-6-methylguanine DNA methyltransferase characterizes a subset of
      colorectal cancer with low-level DNA microsatellite instability.
AB  - The significance of low-level DNA microsatellite instability (MSI-L) is not well
      understood. K-ras mutation is associated with MSI-L colorectal cancer and with
      the silencing of the DNA repair gene O-6-methylguanine DNA methyltransferase
      (MGMT) by methylation of its promoter region. MGMT methylation was studied in
      sporadic colorectal cancers stratified as DNA microsatellite instability-high (n
      = 23), MSI-L (n = 44), and microsatellite-stable (n = 23). Methylation-specific
      PCR was used to detect MGMT-promoter hypermethylation in 3 of 23 (13%)
      microsatellite instability-high, in 28 of 44 (64%) MSI-L, and in 6 of 23 (26%)
      microsatellite-stable cancers (P = 0.0001). K-ras was mutated in 20 of 29 (69%)
      methylated MSI-L cancers and in 2 of 15 (13%) unmethylated MSI-L cancers (P =
      0.001), indicating a relationship between MGMT-methylation and mutation of K-ras.
      Loss of nuclear expression of MGMT was demonstrated immunohistochemically in 23
      of 31 (74%) cancers with methylated MGMT and in 10 of 49 (20%) cancers with
      nonmethylated MGMT (P < 0.0001). Loss of expression of MGMT was also demonstrated
      in 9 of 31 serrated polyps. Silencing of MGMT may predispose to mutation by
      overwhelming the DNA mismatch repair system and occurs with greatest frequency in
      MSI-L colorectal cancers.

PMID- 11221864
TI  - Simultaneous detection of multiple genetic aberrations in single cells by
      spectral fluorescence in situ hybridization.
AB  - Spectral fluorescence in situ hybridization (S-FISH) is a novel molecular
      cytogenetic approach that detects multiple disease-specific chromosomal
      aberrations in interphase nuclei using combinatorial fluorescence and digital
      imaging microscopy. A panel of six centromeric probes for chromosomes 7, 8, 9,
      10, X, and Y, using a unique two-dye combination of four fluorophores, was
      developed to assess ploidy in breast tumors, bladder washings, and leukemia.
      Validation of S-FISH was performed by classic cytogenetics when metaphases were
      available or by standard fluorescence in situ hybridization (FISH) analyses. S
      FISH identified clonal aberrations in newly diagnosed breast tumors and recurrent
      bladder cancer and revealed minimal residual disease in hyperdiploid acute
      lymphocytic leukemia, providing "proof of concept." Like standard FISH,
      aberrations were identified in poor growth/no growth specimen at the single cell
      level; however, S-FISH provided increased sensitivity over standard FISH by
      surveying six genetic targets instead of one or two. Disadvantages of the current
      assay include labor intensive screening and interpretative challenges with signal
      overlap in highly aneuploid samples and focal plane distortions. S-FISH appears
      to be a sensitive oncology assay with significant clinical application for early
      detection of new or reemerging clones, allowing for earlier therapeutic
      intervention and development of probe panels for individualized therapy.

PMID- 11221865
TI  - Loss of Fhit expression is a predictor of poor outcome in tongue cancer.
AB  - Abnormalities of FHIT, a candidate tumor suppressor gene located at 3pl4.2, have
      been found frequently in multiple tumor types, including head and neck squamous
      cell carcinoma. To determine the role of FHIT in tongue cancers, Fhit expression
      was determined by immunohistochemistry studies in tissue samples from 41 patients
      with stages II-IV squamous cell carcinomas of the tongue. All of the patients
      underwent curative surgical treatment with a median of 83 months of follow-up
      care. We found that 28 (68%) of the 41 tumor specimens demonstrated a lack of or
      significantly decreased staining for Fhit. Fhit expression tended to be stronger
      in well-differentiated tumor areas than it was in poorly differentiated areas,
      although this trend was not statistically significant. There was no significant
      correlation between Fhit expression and a patient's age or sex or the
      histological grade or clinical stage of disease. As expected, clinical stage and
      nodal involvement correlated with prognosis. Interestingly, patients whose tumors
      demonstrated low levels of or no Fhit expression had a significantly shorter time
      of disease-free survival than those whose tumors had high Fhit expression (P =
      0.035, by log-rank test). This prognostic value of Fhit was independent of other
      clinical parameters, including stage of disease and nodal status. We conclude
      that Fhit plays an important role in the development of squamous cell carcinomas
      of the tongue and that loss of Fhit expression may be an independent prognostic
      indicator for clinical outcome in patients with this tumor type.

PMID- 11221866
TI  - Vaccination of malignant glioma patients with peptide-pulsed dendritic cells
      elicits systemic cytotoxicity and intracranial T-cell infiltration.
AB  - In this Phase I trial, patients' peripheral blood dendritic cells were pulsed
      with peptides eluted from the surface of autologous glioma cells. Three biweekly
      intradermal vaccinations of peptide-pulsed dendritic cells were administered to
      seven patients with glioblastoma multiforme and two patients with anaplastic
      astrocytoma. Dendritic cell vaccination elicited systemic cytotoxicity in four of
      seven tested patients. Robust intratumoral cytotoxic and memory T-cell
      infiltration was detected in two of four patients who underwent reoperation after
      vaccination. This Phase I study demonstrated the feasibility, safety, and
      bioactivity of an autologous peptide-pulsed dendritic cell vaccine for patients
      with malignant glioma.

PMID- 11221867
TI  - Risk of endometrial cancer and estrogen replacement therapy history by CYP17
      genotype.
AB  - Common variants among genes coding for enzymes in sex steroid biosynthetic
      pathways may influence the risk of endometrial cancer. We examined the
      association between endometrial cancer risk and estrogen replacement therapy
      (ERT) by CYP17 genotype using 51 incident cases and 391 randomly selected
      controls from a multiethnic cohort in Hawaii and Los Angeles, California. The
      relative risk of endometrial cancer was calculated for ever use versus never use
      of ERT by CYP17 genotype (TT, TC, and CC). We found that women who reported ever
      taking ERT were more than twice as likely to develop endometrial cancer as women
      who never took ERT [odds ratio (OR), 2.24; 95% confidence interval (CI), 1.19
      4.23]. Among these women, the risk of endometrial cancer was higher for women
      homozygous for the CYP17 T allele (OR, 4.10; 95% CI, 1.64-10.3), but not for
      women with the C allele (OR, 1.31; 95% CI, 0.53-3.21). These preliminary findings
      suggest that CYP17 or other variants in estrogen biosynthesis or metabolism
      pathways may be potential markers of endometrial cancer susceptibility due to
      ERT.

PMID- 11221868
TI  - Inhibition of epidermal growth factor-induced cell transformation and activator
      protein 1 activation by [6]-gingerol.
AB  - Many spices, including plants of the ginger family, possess anticarcinogenic
      activity. However, the molecular mechanisms by which they exert their
      antitumorigenic effects are unknown. Activator protein 1 (AP-1) has a critical
      role in tumor promotion, and blocking of tumor promoter-induced activation of AP
      1 inhibits neoplastic transformation. Epidermal growth factor induces cell
      transformation and AP-1 activity. The purpose of this study was to investigate
      the effect of two structurally related compounds of the ginger family, [6]
      gingerol and [6]-paradol, on EGF-induced cell transformation and AP-1 activation.
      Our results provide the first evidence that both block EGF-induced cell
      transformation but act by different mechanisms.

PMID- 11221869
TI  - A mammalian two-hybrid system for adenomatous polyposis coli-mutated colon cancer
      therapeutics.
AB  - Colon cancer cells frequently lose expression of the tumor suppressor adenomatous
      polyposis coli (APC). As result, beta-catenin accumulates and activates
      transcription of Tcf-responsive genes. Here we describe a novel mammalian two
      hybrid system that selectively kills APC-mutated cells. This system consists of
      GAL4/beta-catenin, VP16/Tcf4, and a gene that is transcribed when GAL4 and VP16
      associate. In APC-mutated human colon cancer cells, such as SW480, GAL4/beta
      catenin accumulates, and in the presence of VP16/Tcf4, induces high levels of
      expression of the reporter gene. Expression of wild-type APC reduced GAL4/beta
      catenin and intact beta-catenin levels and inhibited reporter gene expression. In
      colon cancer cells such as SW48 that have wild-type APC, GAL4/beta-catenin was
      degraded, and expression levels of the output gene were low. Replacement of the
      reporter gene with a suicide gene resulted in selective killing of SW480 cells.
      This system may be applicable for broader use of gene therapy by targeting
      diseases that involve protein degradation.

PMID- 11221870
TI  - Therapeutic tumor immunity induced by polyimmunization with melanoma antigens
      gp100 and TRP-2.
AB  - To improve the immunogenicity of melanoma self-antigens, we used a novel strategy
      of nonviral genetic vaccination coupled with muscle electroporation.
      Electroporation-enhanced immunization with plasmids encoding either human gp100
      or mouse TRP-2 antigens induced only partial rejection of B16 melanoma challenge.
      However, immunization with a combination of these two antigens caused tumor
      rejection in 100% of the immunized mice. Splenocytes from combination-immunized
      animals killed syngeneic targets loaded with peptides derived from both gp100 and
      TRP-2. Immune cell depletion experiments identified CD8+ T lymphocytes as the
      primary effectors of antitumor immunity. Most importantly, polyimmunization led
      to the generation of a therapeutic immune response that significantly improved
      the mean survival time of mice bearing established lung metastases. These results
      validated the usefulness of electroporation-enhanced, nonviral genetic
      immunization for the active immunotherapy of cancer and indicated that using a
      combination of different tumor antigens may be a decisive strategy for a
      successful therapeutic vaccination.

PMID- 11221871
TI  - Intraneoplastic polymer-based delivery of cyclophosphamide for intratumoral
      bioconversion by a replicating oncolytic viral vector.
AB  - rRp450 is an oncolytic herpesvirus that expresses the CYP2B1 cDNA, responsible
      for bioconverting cyclophosphamide (CPA) into the active metabolites 4
      hydroxyCPA/aldophosphamide (AP). However, formal proof of prodrug activation is
      lacking. We report that activation of CPA in cells infected with rRp450 generates
      a time-dependent increase of diffusible 4-hydroxyCPA/AP. For in vivo
      applications, a CPA-impregnated polymer was implanted into human tumor xenografts
      inoculated with rRp450. The area under the curve for 4-hydroxyCPA/AP was 806
      microg/g of tumor tissue/h when CPA was administered via intraneoplastic polymer
      and 3 microg/g of tumor tissue/h when CPA was administered i.p. Therefore, (a) a
      lytic virus expressing a "suicide" gene can activate a prodrug; and (b) within
      rRp450-infected tumor, more prolonged and higher concentrations of activated
      metabolites are generated by intraneoplastic compared with systemic
      administration of prodrug.

PMID- 11221872
TI  - Identification of a cytotoxic T lymphocyte response to the apoptosis inhibitor
      protein survivin in cancer patients.
AB  - During the last decade, a large number of human tumor-associated antigens have
      been identified that are recognized by CTLs in a MHC-restricted fashion. The
      apoptosis inhibitor protein survivin is overexpressed in most human cancers, and
      inhibition of its function results in increased apoptosis. Therefore, this
      protein may serve as a target for therapeutic CTL responses. Here, using CTL
      epitopes deduced from survivin, we describe specific T-cell reactivity against
      this antigen in peripheral blood from chronic lymphatic leukemia patients and in
      tumor-infiltrated lymph nodes from melanoma patients by ELISPOT analysis. CTL
      responses against two survivin-deduced peptide epitopes were detected in three of
      six melanoma patients and three of four chronic lymphatic leukemia patients. No T
      cell reactivity was detected in peripheral blood lymphocytes from six healthy
      controls. Thus, survivin may serve as an important and widely applicable target
      for anticancer immunotherapeutic strategies.

PMID- 11221873
TI  - Cytotoxic T lymphocytes from HLA-A2.1 transgenic mice define a potential human
      epitope from simian virus 40 large T antigen.
AB  - Recent reports have documented the presence of SV40 large T antigen (T ag)
      sequences in a number of human tumors and raised the question of whether cellular
      immunity to T ag is elicited in such individuals. We used HLA-A2.1 transgenic
      C57BL/6 mice to identify an epitope from T ag recognized by CD8+ CTLs when
      presented by this human MHC class I molecule. Immunization of HLA-A2.1 transgenic
      mice with syngeneic T ag-transformed cells resulted in the induction of HLA-A2.1
      restricted, T ag-specific CTLs. The target epitope, residues 281-289 (KCDDVLLLL)
      of T ag, was identified using both cell lines expressing T ag variants and
      synthetic T ag peptides. Peptide 281-289 bound stably to HLA-A2.1 molecules,
      effectively sensitized target cells for CTL lysis, and was efficiently processed
      from endogenous T ag in cells of both mouse and human origin. CTLs were not cross
      reactive on the human BK or JC virus T ags. Thus, SV40 T ag 281-289 represents a
      potential specific CTL recognition epitope for humans.

PMID- 11221874
TI  - The collaboration of both humoral and cellular HER-2/neu-targeted immune
      responses is required for the complete eradication of HER-2/neu-expressing
      tumors.
AB  - HER-2/neu (neu) transgenic mice (neu-N mice), which express the nontransforming
      rat proto-oncogene, demonstrate immunological tolerance to neu that is similar to
      what is encountered in patients with neu-expressing breast cancer. We have shown
      previously that a significant increase in neu-specific T cells, but no induction
      of neu-specific antibody, is seen after neu-specific vaccination in neu-N mice.
      In contrast, a significant induction of both neu-specific T-cell and antibody
      responses is found in nontoleragenic FVB/N mice after vaccination. These mice are
      fully protected from a s.c. challenge with NT cells, a mammary tumor cell line
      derived from a spontaneous tumor that arose in a neu-N mouse, whereas neu-N mice
      are not. In this study, we demonstrate that CD4+ T cell-depleted FVB/N mice show
      no induction of neu-specific IgG after vaccination and are unable to reject an NT
      challenge (0 of 10 mice were tumor free). Conversely, the depletion of natural
      killer cells has no effect on vaccine-mediated tumor rejection (100% of mice were
      tumor free). In CD8+ T cell-depleted animals, where vaccine-induced neu-specific
      IgG titers were normal, NT growth was delayed, but only 10% of mice remained
      tumor free, demonstrating that neu-specific IgG alone is insufficient for
      protection from NT challenge. To directly assess the necessity for the
      combination of neu-specific cellular and humoral immune responses, severe
      combined immunodeficient mice were given an adoptive transfer of CTLs plus IgG
      derived from FVB/N mice. Animals that were given CTLs that recognized an
      irrelevant antigen plus neu-specific IgG developed tumors at a rate similar to
      CD8+ T cell-depleted FVB/N mice. Animals receiving an adoptive transfer of neu
      specific CTLs plus control IgG derived from naive FVB/N mice were only partially
      protected from NT challenge (50% of animals were tumor free). However, only
      animals receiving the combination of neu-specific CTLs and neu-specific IgG were
      fully protected from NT challenge (100% of animals were tumor free). These
      studies specifically define the immunological requirements for the eradication of
      neu-expressing tumors in this model system, demonstrating that both cellular and
      humoral neu-specific responses are necessary for protection from an NT challenge.
      These data suggest that vaccines optimized to induce maximal T- and B-cell
      immunity to neu, and possibly to similar putative tumor-rejection antigens, may
      lead to more potent in vivo antitumor immunity.

PMID- 11221875
TI  - Interleukin-18 (IL-18) synergizes with IL-2 to enhance cytotoxicity, interferon
      gamma production, and expansion of natural killer cells.
AB  - We investigated the in vitro effects of combining interleukin-18 (IL-18) and IL-2
      on human lymphocytes. The combined use of these two cytokines synergistically
      enhanced the proliferation, cytolytic activity, and interferon-gamma production
      of peripheral blood mononuclear cells. Phenotypic analysis revealed a
      preferential expansion of CD56+CD3- cells and an up-regulation of IL-2 receptor
      alpha expression on natural killer cells. Isolated natural killer cells showed a
      substantial increase in proliferation and cytotoxicity compared with CD4+ and
      CD8+ T cells. The combined use of IL-18 and IL-2 should be considered a viable
      strategy to induce an antitumor response in vivo.

PMID- 11221876
TI  - Differential gene expression profiles of scirrhous gastric cancer cells with high
      metastatic potential to peritoneum or lymph nodes.
AB  - Scirrhous gastric cancer is often accompanied by metastasis to the peritoneum
      and/or lymph nodes, resulting in the highest mortality rate among gastric
      cancers. Mechanisms involved in gastric cancer metastasis are not fully clarified
      because metastasis involves multiple steps and requires the accumulation of
      altered expression of many different genes. Thus, independent analysis of any
      single gene would be insufficient to understand all of the aspects of gastric
      cancer metastasis. In this study, we performed global analysis on differential
      gene expression of a scirrhous gastric cancer cell line (OCUM-2M) and its
      derivative sublines with high potential for metastasis to the peritoneal cavity
      (OCUM-2MD3) and lymph nodes (OCUM-2MLN) in a nude mice model. By applying a high
      density oligonucleotide array method, expression of approximately 6800 genes was
      analyzed, and selected genes were confirmed by the Northern blot method. In our
      observations in OCUM-2MD3 cells, 12 genes were up-regulated, and 20 genes were
      down-regulated. In OCUM-2MLN cells, five genes were up-regulated, and five genes
      were down-regulated. The analysis revealed two functional gene clusters with
      altered expression: (a) down-regulation of a cluster of squamous cell
      differentiation marker genes such as small proline-rich proteins [SPRRs (SPRR1A,
      SPRR1B, and SPRR2A], annexin A1, epithelial membrane protein 1, cellular retinoic
      acid-binding protein 2, and mesothelin in OCUM-2MD3 cells; and (b) up-regulation
      of a cluster of antigen-presenting genes such as MHC class II (DP, DR, and DM)
      and invariant chain (II) in OCUM-2MLN cells through up-regulation of CIITA (MHC
      class II transactivator). We then analyzed six gastric cancer cell lines by
      Northern blot and observed preferential up-regulation of trefoil factor 1, alpha
      1-antitrypsin, and galectin 4 and down-regulation of cytidine deaminase in cells
      prone to peritoneal dissemination. Genes highly correlated with invasion or
      peritoneal dissemination of gastric cancer, such as E-cadherin or integrin beta4,
      were down-regulated in both of the derivative cell lines analyzed in this study.
      This is the first demonstration of global gene expression analysis of gastric
      cancer cells with different metastatic potentials, and these results provide a
      new insight in the study of human gastric cancer metastasis.

PMID- 11221877
TI  - Microsatellite instability and mismatch-repair protein expression in hereditary
      and sporadic colorectal carcinogenesis.
AB  - Aberrant crypt foci (ACF) are microscopic clusters of altered colonic crypts
      considered premalignant lesions in the large bowel. Genomic instability at short
      tandem repeats in the DNA, referred to as microsatellite instability (MSI) is the
      hallmark of hereditary nonpolyposis colorectal carcinoma (HNPCC) caused by
      mutations in DNA mismatch-repair genes, mostly hMLH1 and hMSH2. In this study, we
      evaluated for MSI ACF (n = 16), adenomas (n = 18), carcinomas (n =22), and lymph
      node metastases (n = 3) from 17 patients with colorectal cancer positive for MSI.
      Ten patients were members of HNPCC families; 7 patients had no family history of
      cancer. MSI was found in 7 of 7 (100%) ACF and 11 of 12 (91%) adenomas from
      patients with HNPCC. MSI was not related to histology and size of ACF. A
      progressive increase in instability as estimated by the number of shifted bands
      was observed along the ACF-adenoma-carcinoma sequence. In contrast, two of nine
      (22%) ACF and none of six adenomas from patients with MSI sporadic carcinoma were
      unstable at microsatellite loci. hMLH1 or hMSH2 protein expression was altered
      only in MSI-positive premalignant lesions (ACF and/or adenomas), but not in all
      MSI-positive lesions in patients with HNPCC. These observations provide evidence
      of the premalignant nature of ACF in HNPCC and suggest that MSI is a very early
      event both in HNPCC and in sporadic colorectal carcinogenesis, although in the
      latter it seems infrequent.

PMID- 11221878
TI  - Detection of aberrantly methylated hMLH1 promoter DNA in the serum of patients
      with microsatellite unstable colon cancer.
AB  - Serological tumor markers have proven valuable in the care of individuals with
      cancer for the early detection of primary cancers, early detection of cancer
      relapse, monitoring the response of cancers to therapy, and as predictors of
      cancer prognosis. Recently, the aberrant hypermethylation of the hMLH1 promoter
      and its consequent transcriptional silencing has been shown to be a common event
      in the formation of sporadic microsatellite unstable colon cancer. The silencing
      of hMLH1 expression appears to be controlled by the hypermethylation of a
      specific region in the hMLH1 promoter. We developed a methylation-specific PCR
      assay that assesses this region of the hMLH1 promoter. We found that this assay
      is able to detect methylated hMLH1 promoter DNA in the serum of some patients
      with microsatellite unstable colon cancers. In a panel of sera from 19 colon
      cancer cases, 9 with hMLH1 promoter methylation in the tumor primary, the assay
      proved 33% sensitive and 100% specific. This assay offers a potential means for
      the serum-based detection and/or monitoring of microsatellite unstable colon
      cancers.

PMID- 11221879
TI  - Overexpression of the steroid receptor coactivator AIB1 in breast cancer
      correlates with the absence of estrogen and progesterone receptors and positivity
      for p53 and HER2/neu.
AB  - The gene for the steroid receptor coactivator amplified in breast cancer 1
      (AIBI), located on chromosome 20q12, is overexpressed at the mRNA level in up to
      60% of primary breast carcinomas; however, only 5% of these tumors show DNA
      amplification. The transcription factors and signaling pathways relevant to
      breast cancer, which in the absence of DNA amplification are responsible for and
      targeted by elevated levels of AIBI mRNA, are unknown. In the present study, in
      situ hybridization was used to examine AIB1 mRNA expression in 93 breast
      carcinomas of varying histological grade and immunohistochemical profile. AIB1
      mRNA was overexpressed relative to normal breast tissue in 26 of 83 (31%)
      invasive tumors. This was found to associate with high tumor grade (P = 0.0006),
      lack of immunohistochemical staining for the steroid receptors estrogen receptor
      (P = 0.002) and progesterone receptor (P = 0.002), and strong protein staining
      for p53 (P = 0.01) and HER2/neu (P = 0.002). These findings suggest that AIB1
      overexpression may impact on breast cancer by a mechanism not wholly dependent on
      steroid receptor coexpression and which may involve other oncogenic events, such
      as p53 protein stabilization and HER2/neu overexpression.

PMID- 11221880
TI  - The androgen receptor and genetic susceptibility to ovarian cancer: results from
      a case series.
AB  - Our objectives were to test whether polymorphic variation in the (CAG)n repeat of
      the androgen receptor (AR) gene affects penetrance of germ-line BRCA mutations
      for ovarian cancer or age of diagnosis for ovarian cancer. Using a case-series
      study design, 179 consecutive Ashkenazi Jewish ovarian cancer patients were
      genotyped for AR repeat length and BRCA mutation status. There was no association
      between AR repeat length and presence of a BRCA mutation. However, ovarian cancer
      patients from both groups (with or without BRCA mutation) who carried a short AR
      allele were diagnosed an average of 7.2 (95% confidence interval, 2.3-12.1) years
      earlier than patients who did not carry a short allele (P = 0.004). These data
      suggest that AR allele length affects age of diagnosis of ovarian cancer,
      irrespective of BRCA mutation status.

PMID- 11221881
TI  - Telomere length abnormalities in mammalian radiosensitive cells.
AB  - Telomere lengths in radiosensitive murine lymphoma cells L5178Y-S and parental
      radioresistant L5178Y cells were measured by quantitative fluorescence in situ
      hybridization. Results revealed a 7-fold reduction in telomere length in
      radiosensitive cells (7 kb) in comparison with radioresistant cells (48 kb).
      Therefore, it was reasoned that telomere length might be used as a marker for
      chromosomal radiosensitivity. In agreement with this hypothesis, a significant
      inverse correlation between telomere length and chromosomal radiosensitivity was
      observed in lymphocytes from 24 breast cancer patients and 5 normal individuals.
      In contrast, no chromosomal radiosensitivity was observed in mouse cell lines
      that showed shortened telomeres, possibly reflecting differences in radiation
      responses between primary cells and established cell lines. Telomere length
      abnormalities observed in radiosensitive cells suggest that these two phenotypes
      may be linked.

PMID- 11221882
TI  - Differential binding of the Menin tumor suppressor protein to JunD isoforms.
AB  - The role of the Jun family of proteins (c-Jun, JunB, and JunD) in oncogenesis has
      been extensively studied, but the distinct biological roles of each Jun protein
      is not known. For example, whereas c-Jun can transform primary cells in
      cooperation with an activated ras oncogene, JunD antagonizes ras-mediated
      transformation. We have discovered that two isoforms of the JunD transcription
      factor are ubiquitously expressed, resulting from use of an alternative
      translation start codon within the JunD mRNA. Here we report the first
      characterized functional difference between these JunD isoforms; only the full
      length isoform of JunD binds to the Menin tumor suppressor protein. Furthermore,
      Menin suppresses transcriptional activity of the full-length but not the
      truncated isoform of JunD, which identifies the full-length JunD isoform as a
      functional target of Menin.

PMID- 11221883
TI  - Wilms' tumor suppressor gene (WT1) is expressed in primary breast tumors despite
      tumor-specific promoter methylation.
AB  - We analyzed Wilms' tumor suppressor 1 (WT1) expression and its regulation by
      promoter methylation in a panel of normal breast epithelial samples and primary
      carcinomas. Contrary to previous reports, WT1 protein was strongly expressed in
      primary carcinomas (27 of 31 tumors) but not in normal breast epithelium (1 of 20
      samples). Additionally, the WT1 promoter was methylated in 6 of 19 (32%) primary
      tumors, which nevertheless expressed WT1. The promoter is not methylated in
      normal epithelium. Thus, although tumor-specific methylation of WT1 is
      established in primary breast cancer at a low frequency, other transcriptional
      regulatory mechanisms appear to supercede its effects in these tumors. Our
      results demonstrate expression of WT1 in mammary neoplasia, and that WT1 may not
      have a tumor suppressor role in breast cancer.

PMID- 11221884
TI  - Versican accumulation in human prostatic fibroblast cultures is enhanced by
      prostate cancer cell-derived transforming growth factor beta1.
AB  - We have previously demonstrated that peritumoral stromal matrix derived from
      prostate cancer patients who relapse after radical surgery contains elevated
      levels of versican. The purpose of this study was to determine whether prostate
      cancer cells control stromal cell secretion of versican. Serum-free conditioned
      medium from three prostate adenocarcinoma cell lines, LNCaP, PC3, and DU145, was
      added to cultures of fibroblasts established from prostatic tissue of patients
      with benign prostatic hyperplasia, and the medium was harvested at 24, 48, and 72
      h. Immunoblotting with an antiversican core protein antibody revealed that
      prostatic fibroblast medium harvested at 72 h contained increased levels of
      versican after treatment with either LNCaP-, PC3- or DU145-conditioned medium
      (2.5-, 4.5-, and 5-fold, respectively) compared with control cultures. This
      increase in versican in the culture medium was not observed after coincubation
      with transforming growth factor beta1-neutralizing antisera. The results of this
      study suggest that prostate tumor cells induce host stromal cells to secrete
      increased versican levels via a paracrine mechanism mediated by transforming
      growth factor beta1.

PMID- 11221885
TI  - MS-275, a histone deacetylase inhibitor, selectively induces transforming growth
      factor beta type II receptor expression in human breast cancer cells.
AB  - Transcriptional repression of the transforming growth factor (TGF)-1P type II
      receptor (TPRII) gene appears to be a major mechanism to inactivate TGF-beta
      responsiveness in many human cancers. Because histone acetylation/deacetylation
      plays a role in transcriptional regulation, we have examined the effect of MS
      275, a synthetic inhibitor of histone deacetylase, in human breast cancer cell
      lines. MS-275 showed antiproliferative activity against all human breast cancer
      cell lines examined and induced TbetaRII mRNA, but not TGF-beta type I receptor
      mRNA. MS-275 caused an accumulation of acetylated histones H3 and H4 in total
      cellular chromatin. An increase in the accumulation of acetylated histones H3 and
      H4 was detected in the TbetaRII promoter after treatment with MS-275. However,
      the level of histone acetylation did not change in chromatin associated with the
      TGF-beta type I receptor gene. MS-275 treatment enhanced TGF-beta1-induced
      plasminogen activator inhibitor 1 expression. Thus, antitumor activity of MS-275
      may be mediated in part through the induction of TbetaRII expression and
      consequent potentiation of TGF-beta signaling.

PMID- 11221886
TI  - P73a overexpression is associated with resistance to treatment with DNA-damaging
      agents in a human ovarian cancer cell line.
AB  - We examined the consequences of p73alpha overexpression on gene expression and
      cellular response to anticancer agents in clones from the human ovarian cancer
      cell line A2780. Using microarray filters, the expression of 588 genes in two
      clones overexpressing p73alpha (A2780/p73.4 and A2780/ p73.5) in comparison with
      empty vector-transfected cells was evaluated. There were clear differences in
      gene expression profiles. Both of the clones showed a marked increase in the
      expression of genes involved in DNA repair, including genes participating in
      nucleotide excision repair and mismatch repair. This was confirmed by reverse
      transcription-PCR and Northern blot analysis and was associated with an increase
      in the ability of p73alpha-expressing clones to repair two different DDP (cis
      dichlorodiammine platinum)-damaged plasmids in a host reactivation assay.
      p73alpha overexpressing clones were less sensitive than parental cells to
      alkylating agents treatment or UV radiation but equally sensitive to the
      topoisomerase I inhibitor topotecan, which indicated that the increase in
      expression of DNA repair genes has implications for the response to DNA damaging
      agents.

PMID- 11221887
TI  - Promoter hypermethylation patterns of p16, O6-methylguanine-DNA
      methyltransferase, and death-associated protein kinase in tumors and saliva of
      head and neck cancer patients.
AB  - Aberrant promoter hypermethylation is common in head and neck cancer and may be
      useful as a marker for cancer cells. We examined whether cells with tumor
      specific aberrant DNA-methylation might be found in the saliva of affected
      patients. We tested 30 patients with primary head and neck tumors using
      methylation-specific PCR searching for promoter hypermethylation of the tumor
      suppressor gene p16 (CDKN2A), the DNA repair gene O6-methylguanine-DNA
      methyltransferase (MGMT) and the putative metastasis suppressor gene death
      associated protein kinase (DAP-K). Aberrant methylation of at least one of these
      genes was detected in 17 (56%) of 30 head and neck primary tumors; 14 (47%) of 30
      at p16, 10 (33%) of 30 at Dap-K and 7 (23%) of 30 at MGMT. In 11 (65%) of 17
      methylated primary tumors abnormal methylated DNA was detected in the matched
      saliva samples. Abnormal promoter methylation in saliva DNA was found in all
      tumor stages and more frequently in tumors located in the oral cavity. Moreover,
      none of the saliva from patients with methylation-negative tumors displayed
      methylation of any marker. Of 30 saliva samples from healthy control subjects (15
      smokers and 15 nonsmokers), only one sample from a smoking patient was positive
      for DNA methylation at two target genes. Detection of aberrant promoter
      hypermethylation patterns of cancer-related genes in saliva of head and cancer
      patients is feasible and may be potentially useful for detecting and monitoring
      disease recurrence. Long-term longitudinal studies are needed to evaluate this
      approach for early detection of head and neck cancer in at-risk populations.

PMID- 11221888
TI  - Phorbol esters modulate the Ras exchange factor RasGRP3.
AB  - RasGRP represents the prototype of a new class of guanine nucleotide exchange
      factors that activate small GTPases. The guanyl nucleotide-releasing protein
      (GRP) family members contain catalytic domains related to CDC25, the Ras exchange
      factor of Saccharomyces cerevisiae. They also contain a motif resembling a pair
      of calcium-binding EF-hands and a C1 domain similar to the diacylglycerol
      interaction domain of protein kinase C. The sequence of KIAA0846, identified in a
      human brain cDNA library, encodes a member of the GRP family that we refer to as
      RasGRP3. We show here that RasGRP3 bound phorbol esters with high affinity. This
      binding depended on anionic phospholipids, which is characteristic of phorbol
      ester binding to C1 domain proteins. In addition, phorbol esters also caused
      activation of the RasGRP3 exchange activity in intact cells, as determined by an
      increase in RasGTP and phosphorylation of the extracellular-regulated kinases.
      Finally, both phorbol 12-myristate 13-acetate and the diacylglycerol analogue 1,2
      dioctanoyl-sn-glycerol induced redistribution of RasGRP3 to the plasma membrane
      and/or perinuclear area in HEK-293 cells, as demonstrated using a green
      fluorescent fusion protein. We conclude that RasGRP3 serves as a PKC-independent
      pathway to link the tumor-promoting phorbol esters with activation of Ras
      GTPases.

PMID- 11221889
TI  - High density O-glycosylation of the MUC2 tandem repeat unit by N
      acetylgalactosaminyltransferase-3 in colonic adenocarcinoma extracts.
AB  - A synthetic peptide corresponding to the human MUC2 tandem repeat unit was
      glycosylated in vitro using UDP-GalNAc and extracts of colonic adenocarcinoma and
      paired normal mucosa, followed by fractionation of the products by reverse phase
      high-performance liquid chromatography. Several peaks of glycopeptides with
      different numbers of GalNAc residues attached were detected. It is notable that
      the adenocarcinoma extract was capable of glycosylating peptides to a much
      greater extent than was normal mucosa. The levels of mRNA for N
      acetylgalactosaminyltransferases-1, -2, and -3 were determined by reverse
      transcription-PCR. Only N-acetylgalactosaminyltransferase-3 mRNA was expressed at
      a higher level in the adenocarcinoma than in the normal tissue. When the MUC2
      tandem repeat peptide was glycosylated with a mixture of the normal mucosa
      extract and recombinant N-acetylgalactosaminyltransferase-3, larger amounts of
      glycopeptides with higher contents of GalNAc residues were produced. The MUC2
      tandem repeat peptides glycosylated extensively by recombinant N
      acetylgalactosaminyltransferase-1, -2, or -3 were prepared and characterized.
      Substitution at each Thr residue, as revealed by Edman degradation sequencing, in
      conjunction with evidence obtained on mass spectrometry indicated a heterogeneous
      pattern of site-specific glycosylation within the MUC2 tandem repeat. It was
      found that maximum numbers of 6, 8, and 11 GalNAc residues were incorporated by N
      acetylgalactosaminyltransferases-1, -2, and -3, respectively, and that only N
      acetylgalactosaminyltransferase-3 could completely glycosylate both consecutive
      sequences composed of three and five Thr residues in the MUC2 tandem repeat unit.
      These results suggest that O-glycosylation of the clustered Thr residues is a
      selective process controlled by N-acetylgalactosaminyltransferase-3 in the
      synthesis of clustered carbohydrate antigens.

PMID- 11221890
TI  - Identification of precursor forms of free prostate-specific antigen in serum of
      prostate cancer patients by immunosorption and mass spectrometry.
AB  - The structural features of the free prostate-specific antigen (F-PSA) present in
      human blood have not been clarified up to now, and it is, therefore, not known
      why F-PSA is not complexed by the protease inhibitors that are present in human
      blood in large amounts. This lack of information is mainly attributable to the
      low amount of F-PSA in serum, which makes the isolation and structural
      characterization very difficult, especially when only limited amounts of
      individual sera are available. It has now been demonstrated that F-PSA occurs as
      a mixture of different pro-PSA forms (zymogen forms) in the sera of prostate
      cancer patients, and that, in some of these sera, a form with the regular NH2
      terminus of PSA is present as well. Among the five serum samples investigated,
      all contained the (-7), (-5), and (-4) pro-PSA forms, whereas the (-1) and (-2)
      forms were only present in three of them. These three samples also contained the
      form with the regular NH2 terminus. The (-3) and (-6) pro-PSA forms have not been
      detected thus far. The F-PSA has been isolated by immunosorption from the
      individual sera using streptavidin-coated magnetic beads. The pro-PSA forms were
      identified by matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry after producing peptides by endoproteinase from Lysobacter
      enzymogenes digestion of the SDS-PAGE-separated F-PSA band. The structural
      identity of the (-7)pro-PSA form was further proven by sequencing of that
      particular peptide using electrospray ionization quadrupole time-of-flight mass
      spectrometry.

PMID- 11221891
TI  - Kinase suppressor of ras is necessary for tumor necrosis factor alpha activation
      of extracellular signal-regulated kinase/mitogen-activated protein kinase in
      intestinal epithelial cells.
AB  - Mitogen-activated protein (MAP) kinase activity is essential for tumor necrosis
      factor (TNF) alpha receptor 1 regulation of intestinal epithelial cell
      proliferation. However, the mechanism of TNF-alpha mediated activation of
      extracellular signal-regulated kinase (ERK)/M1AP kinase has not been established
      clearly. Both TNF-alpha and cell-permeable ceramide have been reported to
      increase the kinase activity of kinase suppressor of Ras (KSR). To determine the
      role of KSR in TNF-alpha-induced ERK1/ERK2 activation, we studied young adult
      mouse colon cells expressing a dominant-negative, kinase-inactive (ki) KSR. We
      report that TNF-alpha, a cell-permeable ceramide, and sphingomyelinase stimulate
      ERK1/ERK2 activation and increase the phosphoserine content of KSR, which are
      inhibited by kiKSR expression in intact cells. Furthermore, TNF-alpha-induced Raf
      1 threonine phosphorylation, kinase activity toward MEK1, and association with
      KSR are also inhibited by kiKSR expression. Our data also show by sequential in
      vitro kinase assays that TNF-alpha enhances KSR phosphorylation of Raf-1 on
      threonine, enhancing Raf-1 kinase activity toward MAP kinase kinase. We therefore
      conclude that KSR is an essential upstream regulator of TNF-alpha-stimulated
      ERK1/ERK2 activation, most likely mediated via direct phosphorylation of Raf-1.

PMID- 11221892
TI  - Overexpression of plasminogen activator inhibitor type 2 in basal keratinocytes
      enhances papilloma formation in transgenic mice.
AB  - The serpin plasminogen activator inhibitor (PAI) type 2 is expressed in
      differentiated epidermal keratinocytes. To explore its role in this tissue, we
      studied the impact of PAI-2 overexpression on epidermal differentiation and skin
      carcinogenesis. A mouse PAI-2-encoding transgene was targeted to basal epidermis
      and hair follicles under the control of the bovine keratin type 5 gene promoter.
      Two mouse lines were established, one of which strongly expressed the transgene
      and produced elevated levels of PAI-2 in the epidermis. Although it had no
      manifest impact on cellularity or differentiation of skin or hair follicles, PAI
      2 overexpression rendered the mice highly susceptible to skin carcinogenesis
      induced by a single application of 7,12-dimethylbenz(a)anthracene (initiation)
      followed by twice weekly applications of 12-O-tetradecanoylphorbol-13-acetate
      [TPA (promotion)]. In transgenic mice, papillomas could be observed after 3 weeks
      of promotion; after 8 weeks, 94% (31 of 33) of transgenic mice had developed
      readily visible papillomas, whereas only 35% (7 of 20) of control mice (transgene
      negative littermates) had barely detectable lesions. After 11 weeks, all but 1
      (32 of 33) of the transgenic mice had papillomas as compared with only 65% (13 of
      20) of control mice. After 11 weeks of promotion, application of TPA was
      terminated. In control mice, papillomas regressed and eventually disappeared; in
      transgenic mice, there was continued growth of papillomas, some of which further
      progressed to carcinomas. In contrast to massive apoptosis in regressing
      papillomas of control mice, only a few apoptotic cells were detected in
      transgenic papillomas after the cessation of TPA application. The effect of PAI-2
      on papilloma formation did not appear to involve inhibition of the secreted
      protease urokinase-type plasminogen activator (uPA): PAI-2 accumulated
      predominantly in cells, and PAI-2 overexpression failed to alleviate a phenotype
      induced by uPA secretion, as demonstrated by a double transgenic strategy. In
      addition, in situ hybridization revealed that uPA mRNA is not expressed
      concomitantly with PAI-2 in developing papillomas. We conclude that
      overexpression of PAI-2 promotes the development and progression of epidermal
      papillomas in a manner that does not involve inhibition of its extracellular
      target protease, uPA, but appears to be related to an inhibition of apoptosis.

PMID- 11221893
TI  - Early p53-positive foci as indicators of tumor risk in ultraviolet-exposed
      hairless mice: kinetics of induction, effects of DNA repair deficiency, and p53
      heterozygosity.
AB  - p53 mutations appear to be early events in skin carcinogenesis induced by chronic
      UVB irradiation. Clusters of epidermal cells that express p53 in mutant
      conformation ("p53 positive foci") are easily detected by immunohistochemical
      staining long before the appearance of skin carcinomas or their precursor
      lesions. In a hairless mouse model, we determined the dose-time dependency of the
      induction of these p53+ foci and investigated the relationship with the induction
      of skin carcinomas. The density of p53+ foci may be a good direct indicator of
      tumor risk. Hairless SKH1 mice were exposed to either of two regimens of daily
      UVB (500 or 250 J/m2 broadband UV from Philips TL12 lamps; 54% UVB 280-315 nm).
      With the high-dose regimen, the average number of p53+ foci in a dorsal skin area
      (7.2 cm2) increased rapidly from 9.0 +/- 2.1 (SE) at 15 days to 470 +/- 80 (SE)
      at 40 days. At half that daily dose, the induction of p53+ foci was slower by a
      factor of 1.49 +/- 0.15, very similar to a previously observed slower induction
      of squamous cell carcinomas by a factor of 1.54 +/- 0.02. In a double-log plot of
      the average number of p53 + foci versus time, the curves for the two exposure
      regimens ran parallel (slope, 3.7 +/- 0.7), similar to the curves for the number
      of tumors versus time (slope, 6.9 +/- 0.8). The difference in slopes (3.7 versus
      6.9) is in line with the contention that more rate-limiting steps are needed to
      develop a tumor than a p53+ focus. By the time the first tumors appear (around 7
      8 weeks with the high daily dose), the dorsal skin contains >100 p53+ foci/cm2.
      To further validate the density of p53+ foci as a direct measure of tumor risk,
      we carried out experiments with transgenic mice with an enhanced susceptibility
      to UV carcinogenesis, homozygous Xpa knockout mice (deficient in nucleotide
      excision repair) and heterozygousp53 knockout mice (i.a. partially deficient in
      apoptosis). In both of these cancer-prone strains, the p53+ foci were induced at
      markedly increased rates, corresponding to increased rates of carcinoma
      formation. Therefore, the frequency of p53+ foci appears to correlate well with
      UVB-induced tumor risk.

PMID- 11221894
TI  - Overexpression of membrane-type matrix metalloproteinase-1 gene induces mammary
      gland abnormalities and adenocarcinoma in transgenic mice.
AB  - To investigate the role of membrane-type matrix metalloproteinase-1 (MT1-MMP) in
      mammary gland development and tumorigenesis, transgenic mice overexpressing MT1
      MMP in mammary gland under the control of the mouse mammary tumor virus long
      terminal repeat-promoter were generated. The mouse mammary tumor virus/MT1-MMP
      transgenic mice displayed abnormalities in 82% of female mammary glands. The
      abnormalities were verified as lymphocytic infiltration, fibrosis, hyperplasia,
      alveolar structure disruption, dysplasia, and adenocarcinoma. Northern and
      reverse transcription-PCR analyses demonstrated that MT1-MMP mRNA was
      overexpressed in mammary glands exhibiting abnormalities. Western blot analysis
      and immunohistochemical studies have revealed that the protein expression level
      was also increased in these glands. In addition, the beta-casein gene as a
      functional epithelial cell marker was poorly expressed in the mammary glands of
      transgenic mice exhibiting abnormalities. Gelatin zymography showed significantly
      increased MMP-2 activation in these mammary glands. These results showed that
      overexpression of MT1-MMP induced remodeling of the extracellular matrix and
      tumor formation in the mammary glands of transgenic mice. Therefore, we suggest
      that overexpression of MT1-MMP may play a key role in development and
      tumorigenesis in mammary glands.

PMID- 11221895
TI  - Protoporphyrin IX occurs naturally in colorectal cancers and their metastases.
AB  - Colorectal cancers exhibit a red fluorescence. The nature of the responsible
      fluorophore and its eventual diagnostic potential were investigated. Thirty-three
      consecutive colorectal resection specimen, 32 of which with histologically
      confirmed cancer, and a total of 1053 palpable mesenteric nodes were
      fluorimetrically characterized ex vivo. Furthermore, frozen material from 28
      patients was analyzed, selected for the availability of primary tumor material
      and metastatic tissue, e.g., lymphatic and liver metastases from the same
      patient. Biochemical characterization was carried out through chemical extraction
      and reversed phase high-performance liquid chromatography. The fluorescence
      spectra of tissues, tissue extracts, and standard solutions of porphyrins were
      determined using a pulsed solid-state laser system for excitation and an imaging
      polychromator, together with an intensified CCD camera for time-delayed
      observation. Protoporphyrin IX (PpIX) was identified as the predominant
      fluorophore in primary tumors and their metastases. The fluorophore occurred in
      the absence of necrosis and in sterile locations. In untreated cases (n = 24),
      PpIX fluorescence discriminates metastatically involved lymph nodes from all
      other palpable nodes with a sensitivity of 62% at a specificity of 78% (P <
      0.0001). After neoadjuvant treatment of rectal cancer, the PpIX fluorescence
      level of the primary tumors was reduced and a discrimination of lymph nodes based
      on PpIX-fluorescence was impossible. We conclude that colorectal cancer
      metastases accumulate diagnostic levels of endogenous PpIX as a result of a tumor
      specific metabolic alteration.

PMID- 11221896
TI  - Development of bladder control in children and adolescents with cerebral palsy.
AB  - The study aimed to investigate the development of bladder control in children
      with cerebral palsy (CP) and to determinate subgroups with deviant development of
      bladder control and a higher risk of not achieving urinary continence. Children
      and adolescents between the ages of 4 and 18 years with a diagnosis of CP, from
      six Dutch rehabilitation centres were included in the study (n=601). Parents of
      these participants were sent a questionnaire, of whom 76% responded. Prevalence
      of primary urinary incontinence was 23.5%. Survival curves were made to determine
      the development of achieving bladder control in CP. For participants who achieved
      urinary continence, the development was delayed in comparison with normally
      developing children and adolescents. The most important factors influencing the
      occurrence of urinary incontinence in CP were tetraplegia and low intellectual
      capacity. At age six, 54% of participants with spastic tetraplegia and 80% with
      spastic hemiplegia or diplegia gained urinary continence spontaneously. Of those
      who had low intellectual capacity, 38% were dry at this age.

PMID- 11221897
TI  - Visual impairment due to a dyskinetic eye movement disorder in children with
      dyskinetic cerebral palsy.
AB  - Neurological lesions that cause dyskinetic cerebral palsy (CP) commonly involve
      ocular movements. This report describes a group of 14 children (nine males, five
      females) whose CP is associated with severe dyskinetic eye movements. Ages ranged
      from 4 months to 13 years (mean 6.9 years). Clinical features of this eye
      movement disorder are discussed and defined. The visual function of these
      children is slow, variable, and highly inefficient. They are often misdiagnosed
      as blind, due to cortical visual impairment. Early recognition of dyskinetic eye
      moment disorder and appropriate developmental and educational management are
      important.

PMID- 11221898
TI  - Longitudinal stability of visual evoked potentials in children and adolescents
      with hydrocephalus.
AB  - There were two purposes for this study: to determine the within-subject changes
      of visual evoked potentials (VEPs) over time, and to evaluate the usefulness of
      baseline VEP testing in the early diagnosis of increased intracranial pressure
      (ICP). Twenty children with hydrocephalus between the ages of 4 and 18 years (18
      males, 2 females) were evaluated monthly for up to four months. Flash-evoked VEP
      tests were done in a standardized manner using a Cadwell Quantum 84 evoked
      potential stimulation and recording instrument. One participant had abnormal VEPs
      found during a previous episode of shunt malfunction. For all of the other VEP
      tests, the latency of the N2 response was in the range of adult normal values.
      For 15 participants with multiple evaluations there were non-significant
      differences in N2 latency from one session to the next. This study's results
      provide evidence that within-subject VEP measurements in children with
      hydrocephalus appear to be relatively stable over limited periods. However,
      considerable differences were found when comparing VEPs between participants.
      Further research may provide additional evidence that periodic, routine VEP
      testing is an effective way to monitor individuals who have shunted hydrocephalus
      in order to detect increased ICP before the appearance of obvious symptoms.

PMID- 11221899
TI  - Impact of the therapist-child dyad on children's pain and coping during medical
      procedures.
AB  - This study examined the effects of physical therapists' behaviors on the levels
      of distress and coping of 32 children (19 males, 11 females; age range 2.6 to 9.1
      years) during a painful medical procedure. This is the second study to assess
      children throughout rehabilitation following selective posterior rhizotomy and
      the first to assess the impact of physical therapists' behaviors. Results of the
      Child-Adult Medical Procedure Interaction Scale-Revised confirmed the hypotheses
      that: (1) children exhibit more coping behaviors and fewer distress behaviors
      over time, and (2) positive relationships exist between coping-promoting
      behaviors in physical therapists and coping in children, and distress-promoting
      behaviors in physical therapists and distress in children. Prompts for children
      to use a coping strategy, reassuring comments, and non-procedural talk by
      therapists explained 67% of the variance in children's coping. Criticism,
      reassurance, checking child's status, praise, and empathic statements by
      therapists explained 65% of the variance in children's distress. Older children
      and children with higher IQ scores exhibited more coping behaviors.

PMID- 11221900
TI  - Gliomatosis cerebri in a 10-year-old girl masquerading as diffuse
      encephalomyelitis and spinal cord tumour.
AB  - Gliomatosis cerebri is the unifying term used when diffuse glial infiltration
      occurs throughout the cerebral hemispheres. The very few cases reported in
      children have presented with intractable epilepsy, corticospinal tract deficits,
      unilateral tremor, headaches, and developmental delay. Antemortem diagnosis is
      difficult because of the vagueness of the physical, radiological and pathological
      findings. Adult cases may simulate an acute diffuse encephalomyelitis and show
      postmortem evidence of a marked swelling of the spinal cord. Apparently benign
      intracranial hypertension with papilloedema has also been recorded. We report a
      10-year-old girl who presented with a history and physical signs suggestive of
      benign intracranial hypertension. A diffuse encephalomyelopathy occurred, which
      was complicated by spinal cord swelling, followed by deterioration and death.
      Gliomatosis cerebri affecting the brain and spinal cord was found at postmortem
      examination.

PMID- 11221901
TI  - Prolonged epileptic blindness in an infant associated with cortical dysplasia.
AB  - We report a female infant with status epilepticus amauroticus and intractable
      focal motor seizures associated with congenital cortical dysplasia. EEG
      demonstrated persistent epileptiform discharges over the right parieto-temporal
      regions extending to occipital areas. She required cortical resection of the
      epileptic zone at age 8 months given failure of very high dose antiepileptic
      combinations. Histological analysis of a sample of cortex resected from the right
      central parieto-temporal region, identified by electrocorticography as the focus
      of epileptic activity, showed cortical dysplasia. The seizures ceased and the
      infant gained full vision after 48 hours. During an 8-year follow-up period she
      has had a few short-lived seizures, currently controlled with carbamazepine and
      vigabatrin. Her cognition and speech are intact. This case demonstrates that: (1)
      resection of a central temporo-parietal focus, which may have spread to the
      occipital regions, may result in complete visual recovery and cessation of
      seizures; and (2) EEG should be considered in every infant with alleged delayed
      visual maturation, to rule out concealed epileptic activity.

PMID- 11221902
TI  - Developmental delay and multiple congenital anomalies in a child with a unique
      combination of partial monosomy 18 and partial trisomy 16.
AB  - A male child with multiple congenital anomalies and developmental delay is
      described. Cytogenetic evaluation showed that the patient was partially monosomic
      for the short arm of chromosome 18 and partially trisomic for the short arm of
      chromosome 16: a combination of chromosomal syndromes not previously described.

PMID- 11221903
TI  - Hereditary vitamin-E deficiency.

PMID- 11221904
TI  - Melatonin as a sedation substitute for diagnostic procedures: MRI and EEG.

PMID- 11221905
TI  - Dramatic improvement of severe acute disseminated encephalomyelitis after
      treatment with intravenous immunoglobulin in a three-year-old boy.

PMID- 11221906
TI  - Beliefs about pain among professionals working with children with significant
      neurologic impairment.

PMID- 11221907
TI  - What's in a name?

PMID- 11221908
TI  - Adults with cerebral palsy: a survey describing problems, needs, and resources,
      with special emphasis on locomotion.
AB  - The purpose of this study was to describe problems and resources of adults with
      cerebral palsy (CP) with special emphasis on locomotion. A questionnaire
      concerning demographic facts, locomotion, musculoskeletal problems, and present
      physical activity was mailed to 363 adults with CP. Two hundred and twenty-one
      adults, (125 male and 96 female; mean age 36 years, range 20 to 58 years)
      answered the questionnaire. Seventy-seven per cent reported problems with
      spasticity. Eighty-four per cent lived in their own apartments, with or without
      home services. Twenty-four per cent worked full-time and 18% had full disability
      pension. Twenty-seven per cent had never been able to walk, 64% could walk with
      or without walking aids, 35% reported decreased walking ability, and 9% had
      stopped walking. Eighty per cent reported contractures and 18% had pain every
      day. Approximately 60% were regularly physically active, and despite their
      disability, 54% considered that they were not limited in their ability to move
      about in the community.

PMID- 11221909
TI  - Predicting patterns of interaction between children with cerebral palsy and their
      mothers.
AB  - Children with cerebral palsy (CP) have often been described as passive
      communicators. Their familiar conversation partners tend to direct and control
      interaction. Such conversation patterns may have various precursors: children's
      motor impairment, their intelligibility difficulties, and/or their level of
      cognitive development. To test the comparative influence of these factors,
      measures of motor function, speech, communication, cognitive and language skills
      were applied in 40 children (18 males, 22 females) with CP who were aged from 2
      years 8 months to 10 years. These variables were correlated with measures
      relating to interaction patterns to investigate whether individual features
      predicted communication style. In this group, poor speech intelligibility was the
      main predictor of restrictive communication patterns, such as fewer child
      initiated conversation exchanges, more simple child communicative acts such as
      yes/no answers and acknowledgements of the other partner's messages. Results
      support the provision of therapy to increase children's intelligibility, whether
      spoken or augmented, such as the introduction of communication aids and training
      programmes for parents.

PMID- 11221910
TI  - Cerebral function monitoring in paediatric intensive care: useful features for
      predicting outcome.
AB  - Neurological integrity in sick children is difficult to assess clinically. The
      aim of this study was to determine the predictive value of EEG activity recorded
      with a bedside EEG analysing monitor in an intensive care unit. EEG activity was
      monitored in 108 children (age range 2 weeks to 16 years, median 1.7 years)
      considered at risk for cerebral abnormalities with a cerebral function analysing
      monitor (CFAM). Recordings were evaluated for features of background EEG activity
      including mean amplitude, frequencies, and symmetry. Electrical seizure activity
      was quantified if present. Predictive value of the EEG features was evaluated
      relative to the clinical neurological outcome after one year. Asymmetrical
      recordings were not seen in any child with a normal outcome. Suppression of
      background activity was seen in 75% of the children who died. Seizures were
      present in 68% of children with a poor outcome. Seventeen of the 32 children
      (65%) who died had prolonged seizures. Absence of seizures and the presence of
      superimposed fast EEG activity in response to benzodiazepine infusions correlated
      with good outcome. A combination of two or more predictive EEG features
      demonstrated >90% specificity and positive predictive likelihood of poor outcome.
      EEG features provide information about the functional cerebral integrity of sick
      children. Changes in cerebral activity detected by the CFAM aid decision making
      by providing such information readily at the bedside in intensive care.

PMID- 11221911
TI  - Interobserver reliability of the gross motor performance measure: preliminary
      results.
AB  - Although assessment of the quality of movement in children with cerebral palsy
      (CP) is difficult, the development of the Gross Motor Performance Measure (GMPM)
      has facilitated this process. In order to determine the interobserver reliability
      of the GMPM, 36 children with spastic neuromuscular disorders (mean age 7 years,
      range 4 to 15 years) were evaluated using four of the five dimensions of the
      GMPM. Percent Agreement, Intraclass Correlations, and Kappas were calculated by
      both dimension and attribute to determine reliability. In addition, reliability
      measures were evaluated over time to determine whether reliability improved with
      continual use of the GMPM. Overall, interobserver reliability was in the 'fair to
      good' category regardless of the reliability measure used in the analysis.
      Reliability scores improved over time with a greater number of individual item
      scores moving from the 'fair to good' category to the 'excellent' category.
      Results from this study indicate that it is possible to assess reliably the
      quality of movement in children with CP.

PMID- 11221912
TI  - The relationship between varicocele and semen nitric oxide concentrations.
AB  - We investigated the relationship between seminal plasma nitric oxide (NO)
      concentrations and conventional semen parameters in patients with varicocele.
      Semen samples were obtained from infertile patients with varicocele (n = 55) and
      from normal controls (n = 48). The mean NO concentration in the seminal plasma of
      patients with varicocele was significantly higher than that of the controls (P <
      0.01). A significant negative correlation was noted between NO and sperm motility
      (r = -0.29, P = 0.003), NO and sperm concentration (r = -0.26, P = 0.008) and NO
      and normal morphology (normal %) (r = -0.25, P = 0.01). It was concluded that
      increased NO production may influence sperm production, motility and morphology
      in patients with varicocele.

PMID- 11221913
TI  - Testicular nitric oxide levels after unilateral testicular torsion/detorsion in
      rats pretreated with caffeic acid phenethyl ester.
AB  - Nitric oxide (NO) plays an important role in modulating blood flow in normal and
      in several pathological conditions, and its levels seem to change with ischemia
      reperfusion injuries. Caffeic acid phenethyl ester (CAPE), an active component of
      propolis, exhibits antioxidant properties. This experimental study was designed
      to determine the changes in NO levels and the effect of CAPE on NO levels after
      testicular torsion/ detorsion in rats. Thirty-five adult male albino rats were
      divided into four groups: sham operation (n = 8), torsion (n = 9),
      saline/detorsion (n = 9), and CAPE/detorsion (n = 9). Rats in the sham operation
      group were killed after the testes were handled without torsion. Rats in the
      torsion group were killed after 720 degrees clockwise testicular torsion for 2 h.
      CAPE was administered 30 min before detorsion in the CAPE/detorsion group and
      saline was administered in the saline/detorsion group. After 4 h of testicular
      detorsion in both of these groups, the rats were killed and bilateral orchiectomy
      was performed to determine the tissue levels of NO. The level of NO in the
      torsion group (113.77 +/- 33.18 nmol/g protein) was significantly higher than
      that of the sham operation group (64.53 +/- 29.64 nmol/g protein). In the
      saline/detorsion group, the NO level (31.26 +/- 12.58 nmol/g protein) was
      significantly lower than in the torsion and sham operation groups. CAPE
      administration in the CAPE/detorsion group seemed to raise the NO level (72.63 +/
      23.87 nmol/g protein) above the level of the sham operation group. Contralateral
      testes were not affected by the torsion/detorsion processes performed on the
      ipsilateral testes. These results show that NO levels increase with torsion and
      decrease with detorsion. CAPE administration seems to increase tissue NO levels
      and this may be important for protecting the testes from torsion/detorsion
      injuries.

PMID- 11221914
TI  - Determination of nitric oxide metabolites by means of the Griess assay and gas
      chromatography-mass spectrometry in the cavernous and systemic blood of healthy
      males and patients with erectile dysfunction during different functional
      conditions of the penis.
AB  - Recent research implicated that the relaxation of cavernous arterial and
      trabecular smooth muscle-- the crucial event in penile erection--is initiated by
      the release of nitric oxide (NO) from nerve terminals within the cavernous tissue
      as well as from the endothelia that line the lacunar spaces and the intima of
      penile arteries. The present study was undertaken to determine whether plasma
      levels of the NO metabolites nitrate (NO3-) and nitrite (NO2-) in the systemic
      and cavernous blood of male subjects change during different penile conditions,
      and whether there is a difference in the NO3- and NO2- levels of normal males and
      patients with erectile dysfunction (ED). Twenty-four potent adult male volunteers
      and 15 patients with ED were exposed to visual and tactile erotic stimuli in
      order to elicit penile tumescence and, in the group of healthy volunteers,
      rigidity. Whole blood was aspirated from the corpus cavernosum and the cubital
      vein, and NO3- and NO2- levels were determined in plasma aliquots by means of the
      Griess reaction and a method combining gas chromatography and mass spectrometry
      (GC-MS). The mean systemic and cavernous plasma NO3-/NO2- level in blood samples
      obtained from the healthy volunteers was 25-31 microM when determined by means of
      the Griess reaction and 37-41 microM when measured by GC-MS. Both approaches
      revealed that NO3-/NO2- levels in the peripheral and cavernous blood do not
      change appreciably during developing erection, rigidity and detumescence.
      Moreover, no significant differences were found between NO3-/ NO2- plasma levels
      in the systemic and cavernous blood samples taken from the normal subjects and
      patients during penile flaccidity, tumescence and detumescence. Our results may
      reflect the fact that NO metabolism in the corpora cavernosa in the phases of
      penile tumescence and rigidity may account for only a minor fraction of local
      levels of NO3- and NO2-, which may also derive from exogenous sources. Moreover,
      the basal levels of NO metabolites in the blood flushing the lacunar spaces of
      the cavernous body in the state of developing erection could conceal any release
      of NO that may occur within the penile tissue. Thus, we conclude that the
      quantification of NO metabolites by means of advanced detection methods, such as
      GC-MS, is of no use in the workup of ED.

PMID- 11221915
TI  - Effects of cotinine on sperm motility, membrane function, and fertilizing
      capacity in vitro.
AB  - We evaluated the effect of cotinine on sperm fertilizing capacity in vitro. Human
      spermatozoa were washed and re-suspended in medium containing albumin and various
      concentrations of cotinine (0, 100, 200, 400, or 800 ng/ml). After an 8-h
      incubation period, sperm motility, hypoosmotic swelling test (HOST) outcome, and
      the percentage of hyperactivated spermatozoa were assayed. Aliquots of
      spermatozoa were then processed for the zona-free hamster oocyte sperm
      penetration assay (SPA) or hamster ooplasmic injections. Spermatozoa exposed to
      concentrations of cotinine equal to 400 or 800 ng/ml demonstrated significantly
      smaller outcomes for all of the above with the exception of after hamster
      ooplasmic injections, where high cotinine concentrations did not affect sperm
      viability or sperm capacity to undergo decondensation and activate hamster
      oocytes. It appears that cotinine concentrations of 400 or 800 ng/ml exert a
      detrimental effect on sperm motility, membrane function, and the ability to
      undergo capacitation. In addition, the current findings suggest that smokers with
      a high seminal plasma cotinine concentration who participate in assisted
      reproduction programs may be treated with intracytoplasmic sperm injections
      (ICSI) rather than conventional in vitro fertilization (IVF) trials.

PMID- 11221916
TI  - Diclofenac and NS-398, a selective cyclooxygenase-2 inhibitor, decrease agonist
      induced contractions of the pig isolated ureter.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are currently considered a first
      line treatment of renal colic. Their action has been ascribed to the inhibition
      of renal prostaglandin synthesis, which decreases renal blood flow and diuresis,
      and consequently lowers the pressure in the renal pelvis and ureter. However, the
      effects of NSAIDs on induced contractions of ureteral smooth muscle have received
      little attention. Also, there is a lack of clinically relevant spasmolytic drugs
      for the ureter. Therefore, we studied the influence of the non-selective
      cyclooxygenase (COX) inhibitor diclofenac, a NSAID drug customarily used in the
      treatment of renal colic, and of NS-398, a selective COX-2 inhibitor, on induced
      contractions of the pig ureter. Serotonin (0.1-30 microM), norepinephrine (0.1-30
      microM) and neurokinin A (0.03-10 microM) induced reproducible concentration
      dependent contractions, which were inhibited by diclofenac and NS-398 (10-300
      microM) in a concentration-dependent manner. The sensitivity of neurokinin A
      induced contractions to diclofenac was 3-4 times greater than that of the amines.
      Depending on the concentration, inhibition ranged between 25 and 96% of the
      initially induced contractile activity. In the presence of inhibitors,
      supramaximal concentrations of agonists were unable to trigger recuperation of
      the initially induced contractions. Prostaglandin F2alpha did not reverse the
      effect of diclofenac on agonist-induced contractions. Removal of diclofenac or NS
      398 from the organ baths showed that the inhibition was totally reversible. Thus,
      the non-selective COX inhibitor diclofenac and the selective COX-2 inhibitor NS
      398 are almost equipotent in reducing agonist-induced contractions in the
      isolated porcine ureter. Although the clinical relevance of this spasmolytic
      effect remains to be demonstrated, the data suggest that patients suffering from
      renal colic may benefit not only from the anti-diuretic and analgesic effects of
      diclofenac, but also from its potential spasmolytic properties. Moreover,
      selective COX-2 inhibitors may have clinical potential, as they may cause fewer
      side effects.

PMID- 11221917
TI  - Ex vivo stimulation of renal tubular p-aminohippurate transport by dexamethasone
      and triiodothyronine in human renal cell carcinoma.
AB  - This paper is the third of a long-term planned series of papers dealing with ex
      vivo investigations of drug transport in human kidney. The aims of this study are
      (a) to investigate whether or not human renal cell carcinoma (RCC) can actively
      accumulate p-aminohippurate (PAH) and (b) to test the response of RCC on
      dexamethasone or triiodothyronine (T3) using tissue slices ex vivo. By this
      approach, the accumulation capacity of RCC should be stimulated as a prerequisite
      for an increased uptake of anti-tumour drugs. Tissue slices of RCC samples of 30
      patients were incubated for 24 h in Williams medium E containing 0.01-50 microM
      dexamethasone or T3. Thereafter, slices were placed in PAH-containing Cross
      Taggart medium, and PAH uptake into kidney tissue was measured for 2h under
      standardised conditions as described previously. In intact human renal cortical
      slices, PAH uptake capacity, expressed as slice to medium ratio (QS/M), was about
      2.8 +/- 0.16 after 24 h of incubation and increased significantly in
      dexamethasone-containing medium in a concentration-dependent manner, up to
      approximately 150%, whereas T3 did not influence PAH accumulation. On the other
      hand, in RCC the PAH accumulation capacity was completely abolished (QsM
      approximately 1). However, after administration of dexamethasone, the accumulated
      amount of PAH increased significantly in RCC tissue in a concentration-dependent
      manner, up to approximately 190%. T3 was without effect in RCC, too.
      Surprisingly, the dexamethasone-mediated stimulation could be differentiated into
      responders and non-responders, with maximal effects at different concentrations
      for each patient. Nevertheless, the maximal transport rates remained low in RCC,
      even under hormone influence. In conclusion, a moderate stimulation of tubular
      transport capacity can be shown ex vivo in human RCC. This phenomenon is only of
      a relatively low degree compared with intact renal tissue. However, in principle,
      the response of RCC on dexamethasone could form a basis for further therapeutic
      strategies to overcome multi-drug resistance in RCC patients. For this purpose,
      additional experiments analysing the expression of transporters of the ABC
      cassette-type are in progress.

PMID- 11221918
TI  - Potentiation of effects of anticancer agents by local electric pulses in murine
      bladder cancer.
AB  - Electrochemotherapy is a novel cancer treatment in which electric pulses (EP) are
      used as a means of delivering anticancer agents to the cytoplasm of cancer cells
      (electroporation). The present study evaluates whether electrochemotherapy has in
      vitro and in vivo anticancer effects in murine bladder cancer. Using mouse
      bladder tumor cells (MBT-2 cells), in vitro electrochemotherapy was performed by
      applying EP to the cell suspension immediately after the addition of anticancer
      agents. The cytotoxicity of adriamycin (ADM), bleomycin (BLM) and cis
      diamminedichloroplatinum(II) (CDDP) was determined by measuring succinate
      dehydrogenase (SD) activity in both electroporated and non-electroporated cells.
      In addition, intracellular concentrations of these anticancer agents were also
      measured. In the in vivo study, tumor-bearing C3H/He mice were treated with an
      intraperitoneal injection of anticancer agents followed by a local delivery of EP
      at the tumor site. Then, tumor growth rate (TGR) was determined and compared to
      that in the sham-treated control group, the EP-only group and the drug-only
      group. The in vitro study showed that, with electroporation, the cytotoxicity of
      BLM in electroporated cells was increased by as much as 95.7-fold compared to
      that of non-electroporated MBT-2 cells; CDDP showed only an increase of 1.8-fold
      and ADM showed no increase. After electroporation, the intracellular
      concentration of BLM, CDDP and ADM showed an increase of 120-, 1.7- and 0.8-fold,
      respectively. In electrochemotherapy for in vivo growing tumors, the potentiation
      of the antitumor effect was most prominent when combined with BLM, only slightly
      with CDDP, and totally absent with ADM. It is clear from in vitro and in vivo
      studies that, in a murine bladder tumor, the anticancer effect of BLM can be
      considerably potentiated by applying EP. Thus, BLM seems to be the most suitable
      anticancer agent for electrochemotherapy of bladder cancer.

PMID- 11221919
TI  - Expression of MAGE antigens and analysis of the inflammatory T-cell infiltrate in
      human seminoma.
AB  - The MAGE gene family encodes antigens that are recognized by cytotoxic T-cells.
      The expression of MAGE antigens has been linked to tumor stage, and MAGE peptides
      are under investigation as possible vaccines. Seminomas are tumors that are
      typically accompanied by a heavy inflammatory infiltrate, but have not been
      studied with regard to their MAGE antigen expression and its correlation with the
      inflammatory infiltrate. We investigated, therefore, MAGE protein expression, the
      amount of cytotoxic T-cells, clonality of the lymphocytic infiltrate, apoptotic
      activity and occurrence of necrosis. Specimens of 27 patients with classical
      seminoma were examined by immunohistochemistry for CD4, CD8, CD56, CD45R0, beta2
      microglobulin and HLA-DR. MAGE expression was detected with the monoclonal
      antibody 57B, reactive with MAGE-1, -3, -4, -6 and -12. Clonality of the
      inflammatory infiltrate was examined by multiplex polymerase chain reaction (PCR)
      analysis of the T-cell receptor rearrangement. Apoptotic cells were detected by
      DNA nick-end labeling of fragmented DNA, and the apoptotic index was determined
      semi-quantitatively. Expression of 57B was found in 19 (70%) of 27 seminomas. In
      all cases, more than 70% of T-cells expressed CD45R0. In four cases, a
      predominant infiltration of CD8-positive cytotoxic T-cells (CD4/CD8 ratio < 1)
      was present. However, 15 seminomas showed a CD4/CD8 ratio > 1. In all cases,
      infiltration of CD56-positive natural killer cells was only focal. HLA-DR
      expression was not detectable in tumor tissue; beta2-microglobulin was only focal
      in three cases. Analysis of the T-cell clonality revealed a polyclonal
      population. The apoptotic index was not significantly different in 57B-positive
      seminomas (4.15%) compared with 57B negative seminomas (3.80%). Also, no
      correlation between the 57B expression and the occurrence of necrosis was found.
      MAGE antigens are homogeneously expressed in most seminomas, but their presence
      does not appear to represent a dominant epitope responsible for the lymphocytic
      infiltrate.

PMID- 11221920
TI  - Nephrocalcinosis and hyperlipidemia in rats fed a cholesterol- and fat-rich diet:
      association with hyperoxaluria, altered kidney and bone minerals, and renal
      tissue phospholipid-calcium interaction.
AB  - To determine whether an "atherogenic" diet (excess of cholesterol and neutral
      fat) induces pathological calcification in various organs, including the kidney,
      and abnormal oxalate metabolism, 24 male Sprague-Dawley rats were fed either
      normal lab chow (controls, n = 12) or the cholesterol- and fat-rich experimental
      diet (CH-F, n = 12) for 111 +/- 3 days. CH-F rats developed dyslipidemia [high
      blood levels of triglycerides, total, low-density lipoprotein (LDL)-, very low
      density lipoprotein (VLDL)-, high-density lipoprotein (HDL)-bound cholesterol,
      total phospholipids], elevated serum total alkaline phosphatase and lactate
      dehydrogenase (LDH) levels, in the absence of changes in overall renal function,
      extracellular mineral homeostasis [serum protein-corrected total calcium,
      magnesium, parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25(OH)2D)],
      plasma glycolate and oxalate levels. There was a redistribution of bone calcium
      and enhanced exchange of this within the extraosseous space, which was
      accompanied by significant bone calcium loss, but normal bone histomorphometry.
      Liver oxalate levels, if expressed per unit of defatted (DF) dry liver, were
      three times higher than in the controls. Urinary glycolate, oxalate, calcium and
      total protein excretion levels were elevated, the latter showing an excess of
      proteins > 100 kD and a deficit of proteins > 30-50 kD. Urinary calcium oxalate
      supersaturation was increased, and calcium phosphate supersaturation was
      unchanged. There were dramatically increased (by number, circumference, and area)
      renal calcium phosphate calcifications in the cortico-medullary region, but
      calcium oxalate deposits were not detectable. Electron microscopy (EM) and
      elemental analysis revealed intratubular calcium phosphate, apparently needle
      like hydroxyapatite. Immunohistochemistry of renal tissue calcifications revealed
      co-localization of phospholipids and calcium phosphate. It is concluded that rats
      fed the CH-F diet exhibited: (1) a spectrum of metabolic abnormalities, the more
      prominent being dyslipidemia, hyperoxaluria, hypercalciuria, dysproteinuria, loss
      of bone calcium, and calcium phosphate nephrocalcinosis (NC); and (2) an
      interaction between calcium phosphate and phospholipids at the kidney level. The
      biological significance of these findings for the etiology of idiopathic calcium
      urolithiasis in humans is uncertain, but the presented animal model may be
      helpful when designing clinical studies.

PMID- 11221921
TI  - Chromium speciation in liquid matrices: a survey of the literature.
AB  - A thorough review of the literature published (1983 - March 1999) on chromium
      speciation in liquid samples is presented, and analytical techniques used in the
      404 articles are summarized. The discussion focuses on atomic spectrometric
      techniques, which are mainly employed for chromium speciation in liquid matrices
      (134 articles). Details on the type of pretreatment, species, samples, techniques
      and analytical features of the methodologies proposed are given.

PMID- 11221922
TI  - Enhanced sensitivity for Os isotope ratios by magnetic sector ICP-MS with a
      capacitive decoupling Pt guard electrode.
AB  - A magnetic sector ICP-MS with enhanced sensitivity was used to measure Os isotope
      ratios in solutions of low Os concentration (approximately 1 ng g(-1) or less).
      Ratios with 192Os as the basis were determined, while the geologically useful
      187Os/188Os ratio was also measured. Sample introduction was via the traditional
      nebuliser-spray chamber method. A capacitive decoupling Pt shield torch was
      developed "in-house" and was found to increase Os signals by approximately 5 x
      under "moderate" plasma conditions (1050 W) over that found during normal
      operation (1250 W). Sensitivity using the guard electrode for 192Os was
      approximately 250-350,000 counts s(-1) per ng g(-1) Os. For a I ng g(-1) Os
      solution with no guard electrode, precisions of the order of 0.2-0.3%
      (189Os/192Os and 190Os/192Os) to approximately 1% or greater (186Os/192Os,
      187Os/192Os and 187Os/188Os) were found (values as 1 sigma for n = 10). With the
      guard electrode in use, ratio precisions were found to improve to 0.2 to 0.8%.
      The total amount of Os used in the acquisition of this data was approximately 2.5
      ng per measurement per replicate. At the higher concentration of 10 ng g(-1),
      precisions of the order of 0.15-0.3% were measured (for all ratios), irrespective
      of whether the shield torch was used. Ratio accuracy was confirmed by comparison
      with independently obtained NTIMS data. For both Os concentrations considered,
      the improvement in precision offered by the guard electrode (if any) was small in
      comparison to calculated theoretical values based on Poisson counting statistics,
      suggesting noise contributions from other sources (such as the sample
      introduction system, plasma flicker etc). At lower Os concentrations (to 100 pg
      g(-1)) no appreciable loss of ratio accuracy was observed, although as expected
      based on counting statistics, poorer precisions of the order of 0.45-3% (1 sigma,
      n = 5) were noted. Re was found to have a detrimental effect on the precision of
      Os ratios involving 187Os, indicating that separation of Re and Os samples is a
      necessary pre-requisite for highly accurate and precise Os isotope ratio
      measurements.

PMID- 11221923
TI  - Identification of chemical substances by testing and screening of hypotheses. I.
      General.
AB  - The characteristic features and the constituents of an identification procedure
      for chemical substances are discussed. This procedure is a screening of
      identification hypotheses followed by experimental testing of each one. The
      testing operation consists of comparison of the values of the quantities measured
      with other measurement results or reference data, resulting in the Student's
      ratio, the significance level, the matching of spectra, etc. The performance and
      the correctness of identification are expressed as "identification uncertainty",
      i.e. the probability of incorrect identification. The statistical significance
      level and other similarity values in spectra, chromatography retention
      parameters, etc. are the particular measures of uncertainty. Searching of prior
      data and estimation of the prior probability of the presence of particular
      compounds in the sample (matrix) to be analysed simplifies the setting up and
      cancelling of hypotheses during screening. Usually, identification is made by the
      analyst taking into account measurement results, prior information and personal
      considerations. The estimation of uncertainty and rules for the incorporation of
      prior data, make the result of identification less subjective.

PMID- 11221924
TI  - Identification of chemical substances by testing and screening of hypotheses. II.
      Determination of impurities in n-hexane and naphthalene.
AB  - The impurities in n-hexane and naphthalene are identified by gas chromatography
      and mass spectrometry when applying the multiple criteria of identification. The
      identification uncertainty is expressed by the significance level, the difference
      in retention indexes and the mass spectra fit value. Identified impurities are
      substances which are rather abundant in nature/practice/research and rather
      frequently co-cited with matrix substance in chemical literature. This regularity
      is discussed with reference to statistical treatment of chemical database as a
      means to screen identification hypotheses.

PMID- 11221925
TI  - Improvements in calibration procedures for the quantitative determination of
      trace elements in carbonate material (mussel shells) by laser ablation ICP-MS.
AB  - A better repeatability and accuracy in the quantitative determination of trace
      elements in mussel shells or carbonate-based materials by LA-ICP-MS was achieved
      by using a series of multielement calibration standards prepared by co
      precipitation of twelve elements into a CaCO3 matrix in order to improve the
      homogeneity of the resulting powder samples. Pressed powder discs of good
      mechanical stability could be obtained at a pressure of 50 MPa, without the
      addition of a binder. An UV laser (modified Nd:YAG, 266 nm) was used in the Q
      switched mode at a repetition rate of 10 Hz and an energy level of 3.5 mJ.
      Correlation coefficients (R) for the linear calibration graphs (concentration
      range: 1.5-400 microg/g) for Cr, Mn, Co, Cu, Zn, As, Cd, Sn, Ba, and Pb are
      generally better than 0.997. The detection limits for all elements investigated
      are in the sub-microg/g range. Incorporation of elements into the matrix by co
      precipitation has shown as a superior method for producing calibration standards
      than the simple mixture of the analytes (in carbonate or oxide form) with the
      matrix (CaCO3) or addition of standard solutions to a carbonate powder base. Two
      examples of the quantitative determination of toxic elements in mussel shells
      will be presented.

PMID- 11221926
TI  - Analysis of inorganic anions by electrostatic ion chromatography using
      zwitterionic/cationic mixed micelles as the stationary phase.
AB  - The inability to separate fluoride, phosphate and sulfate by electrostatic ion
      chromatography (EIC) was overcome by using an ODS silica column coated with mixed
      zwitterionic-cationic surfactants as the stationary phase. The best results were
      obtained using the zwitterionic surfactant, 3-(N,N-dimethylmyristylammonium)
      propanesulfonate (C19H41NO3S), and the cationic surfactant,
      myristyltrimethylammonium, CH3(CH2)13N+(CH3)3, in a 10:1 molar ratio in the
      column coating solution. With a dilute solution of sodium tetraborate as the
      eluent the model analyte anions were completely separated in the following
      elution order: F, HPO42-, SO42-, Cl-, NO2-, Br-, NO3-. The very early elution of
      phosphate and sulfate is most unusual and is unique to this system. Detection
      limits better than 1.1 x 10(-4) mM and linear calibration plots up to 7.0 mM were
      obtained with a suppressed conductivity system.

PMID- 11221927
TI  - Kinetic spectrophotometric determination of traces of sulfide in nonionic
      micellar medium.
AB  - A sensitive kinetic spectrophotometric method for the determination of ng amounts
      of sulfide has been developed based on the reduction of Azure A by sulfide in the
      presence of Brij-35 at pH 7. The decrease in absorbance of Azure A at 600 nm is
      proportional to the concentration of sulfide over the range 25-1,400 ng mL(-1).
      The variables affecting the rate of the reaction were investigated and the
      optimum conditions were established. The method is simple, rapid, precise,
      sensitive, and widely applicable. The limit of detection is 17 ng mL(-1), and the
      relative standard deviation of seven determinations of 500 ng mL(-1) sulfide was
      2.1%. The method was applied to the determination of sulfide in spring water.

PMID- 11221928
TI  - Photokinetic voltammetric method for the determination of thiocyanate.
AB  - Thiocyanate traces have a strong inhibitory effect on the oxidation of Neutral
      Red by potassium bromate under UV irradiation in diluted phosphoric acid. Neutral
      Red exhibits a sensitive second derivative oscillopolarographic wave at -0.6
      V(vs. SCE) in diluted phosphoric acid and sodium acetate solution. The
      oscillopolarographic behavior of Neutral Red was selected as indicator component
      for its photo-activated oxidation. The photochemical reaction rate equation was
      determined. A detection limit of 0.3 ng mL(-1) (3sigma/k) and a linear
      calibration curve from 2.0-48.0 ng mL(-1) thiocyanate were obtained. The method
      was applied to the determination of thiocyanate in urine, saliva and serum with
      satisfactory results.

PMID- 11221929
TI  - On-line complexation of zinc with 5-Br-PADAP and preconcentration using a knotted
      reactor for inductively coupled plasma atomic emission spectrometric
      determination in river water samples.
AB  - An on-line zinc preconcentration and determination system implemented with
      inductively coupled plasma atomic emission spectrometry (ICP-AES) associated with
      flow injection (FI) was studied. The zinc was retained as zinc-2-(5-bromo-2
      pyridylazo)-5-diethylaminophenol (Zn-(5-Br-PADAP)) complex at pH 9.2. The zinc
      complex was removed from the knotted reactor (KR) with 30% v/v nitric acid. An
      enrichment factor of 42 was obtained for the KR system with respect to ICP-AES
      using pneumatic nebulization. The detection limit for the preconcentration of 10
      mL of aqueous solution was 0.09 microg/L. The precision for 10 replicate
      determinations at the 5 microg/L Zn level was 2.3% relative standard deviation
      (RSD), calculated with the peak heights obtained. The calibration graph using the
      preconcentration system for zinc was linear with a correlation coefficient of
      0.9997 at levels near the detection limits up to at least 100 microg/L. The
      method was succesfully applied to the determination of zinc in river water
      samples.

PMID- 11221930
TI  - Fluorometric determination of Ethofenprox in water by using solid-phase
      extraction.
AB  - Ethofenprox (pesticide) exhibits a relatively strong fluorescence in the UV
      region. Its fluorescence properties were investigated in aqueous solution,
      organic solvents, and micellar media. The fluorescence intensity of Ethofenprox
      was enhanced by a factor of 1.2 to 2.7 in the presence of surfactants and by 1.4
      in pure organic solvents without significant shift of the excitation and emission
      wavelengths. The conditions for solid-phase extraction of Ethofenprox from water
      samples were examined. Among the solid-phase extraction cartridges studied, a Sep
      Pak C8 with weak sorption ability was found to be the most useful due to the
      extremely high hydrophobicity of Ethofenprox. For the complete elution of
      Ethofenprox from the sorbent, an addition of 40%v/v methanol to the sample water
      was necessary and effective to eliminate the fluorescent impurities of the
      matrix. The calibration graph obtained was linear over the range of 0.03 to 2.4
      mg L(-1) in 100 mL sample. The method was successfully applied to the
      determination of Ethofenprox in tap, well, and river waters with recoveries of
      93.2-95.7%.

PMID- 11221931
TI  - HPLC separation of flavonols, flavones and oxidized flavonols with UV-, DAD-,
      electrochemical and ESI-ion trap MS detection.
AB  - The cation-induced or electrochemical oxidation of flavonols has been reported to
      yield 2-(hydroxybenzoyl)-2-hydroxy-3(2H)-benzofuranone. Two new gradient reversed
      phase HPLC methods are presented which allow the determination of those oxidized
      flavonols simultaneously with flavonols and flavones. UV and electrochemical
      detection are used because of their high sensitivity. Qualitative detection
      together with quantification of all compounds is achieved with photodiode-array
      detection. An electrospray ionization ion trap mass spectrometric method is
      presented for unique identification of the benzofuranones after HPLC separation.

PMID- 11221932
TI  - Sensitive detection of a plant virus by electrochemical enzyme-linked
      immunoassay.
AB  - The electrochemical enzyme-linked immunoassay increases the sensitivity of the
      detection of cucumber mosaic virus (CMV) by 5-fold compared with the
      spectrophotometric o-phenylenediamine (OPD) enzyme-linked immunosorbent assay
      (ELISA). The detection limit for the purified CMV is 1.0 ng/mL and the highest
      dilution ratio of the infected leaf sap is 1:5.0 x 10(4). The method is based on
      coupling the oxidation reaction of o-aminophenol (OAP)-H2O2 catalyzed by HRP-IgG
      conjugate with the electro-reduction of the enzymatic product. The enzymatic
      product 2-aminophenoxazine-3-one exhibits a sensitive second order derivative
      linear-sweep voltammetric response at the potential of -0.65 V (vs. Ag/AgCl) in
      pH 8.0 Britton-Robinson (B-R) buffer solution. So it can be applied to the
      detection of the plant virus with highly improved sensitivity.

PMID- 11221933
TI  - Flow injection analysis with in-line solid phase extraction for the
      spectrophotometric determination of sulfonated and unsulfonated Quinoline Yellow
      in Cologne.
AB  - An integrated solid-phase spectrophotometry/ FIA method is proposed for the
      determination of the synthetic colorant matter Quinoline Yellow (QYWS) in the
      presence of its unsulfonated derivative QYSS. The procedure is based on the
      retention and preconcentration of the low level QYSS on a C-18 silica gel
      minicolumn, followed by sequential measurement of its absorbance at lambda = 410
      nm after its elution with methanol. The applicable concentration range, the
      detection limit and the relative standard deviation were the following: for QYWS,
      from 0.10 to 30.0 mg L(-1); 0.013 mg L(-1); and 0.6%; and for QYSS, between 10
      and 1.000 microg L(-1); 2 microg L(-1); and 1.3%, respectively. The method was
      applied to the determination of small amounts of QYSS present in QYWS in
      Colognes. Percentages of recovery between 98% and 99% were obtained in all
      instances. The method was also satisfactorily applied to the determination of
      these compounds in samples of commercial Colognes comparing the results for QYWS
      with those offered by an HPLC reference method and also validating the results
      chemometrically.

PMID- 11221934
TI  - Von Hippel-Lindau gene therapy: a novel strategy in limiting endothelial cell
      proliferative activity.
AB  - There is evidence that loss of function of the von Hippel-Lindau (VHL) gene
      causes transcriptional activation of the vascular endothelial growth factor
      (VEGF) gene, which in turn may lead to increased proliferation of vascular
      endothelial cells. We hypothesized that transfer of VHL gene, a tumor suppressor
      gene, into vascular endothelial cells could cause loss of viability and
      suppression of its proliferative ability. Human aortic endothelial cells (HAEC)
      were grown as monolayers and transfected with varying titers of adenovirus
      containing the VHL cDNA (AdVHL). The negative controls used were adenovirus
      containing green fluorescent protein (AdGFP), vector alone (AdNull), and
      infection medium without virus. Adenovirus encoding p53 (Adp53) was used as
      positive control. Cell viability and proliferation were determined by trypan blue
      dye exclusion and by a tetrazolium-based colorimetric assay. All experiments were
      performed in triplicate. Our results showed that proliferative activity in HAEC
      can be blocked and viability of HAEC reduced by adenovirus-mediated gene transfer
      of VHL gene. This is the first time that VHL gene has been effectively
      transferred to HAEC. VHL gene transfer into the vascular endothelium may have
      potential in limiting proliferative processes, including intimal hyperplasia.

PMID- 11221936
TI  - The hemodynamics of vein grafts: measurement and meaning.
AB  - The long-term patency of infrainguinal vein grafts appears to depend primarily on
      the size and quality of the venous conduit. Therefore, those quantities which
      directly relate to the conduit's ability to act as a transporter of blood, namely
      internal diameter and longitudinal impedance (Z(L)), have predictive value for
      patency. Autologous grafts of good quality frequently remain patent even with
      compromised outflow. Therefore, those quantities that are outflow dependent,
      including deltaP, flow, velocity, shear stress, and resistance, carry less
      predictive value for long-term performance.

PMID- 11221935
TI  - Reduction in wound morbidity rates following endoscopic saphenous vein harvest.
AB  - To determine whether less-invasive saphenous vein harvest reduces morbidity in
      patients undergoing infrainguinal bypass, we retrospectively compared 61 patients
      undergoing endoscopic harvest (ENDO) with 49 patients undergoing conventional
      harvest (OPEN) over the past 13 months. Patients were classified as potential
      short-stay if adjunctive suprainguinal inflow procedures or foot amputations were
      not required and the patient was ambulatory prior to elective operation. Mean
      endoscopic harvest time was 50+/-18 (range 25-90) min, and no more than three 5
      cm incisions were required in 87% of cases. Szilagyi class II or III wound
      complications occurred after 1 of the 61 (2%) ENDO procedures and 7 of the 49
      (14%) OPEN (p < 0.01), and any complication occurred in 13 (21%) vs. 25 (51%) of
      ENDO and OPEN procedures, respectively (p < 0.002). Mean postoperative length of
      stay was significantly shorter in the 24 short-stay ENDO (4.0+/-2.4 days) vs. 25
      short-stay OPEN (6.0+/-3.2 days) patients (p < 0.02). Thirty-day patency rates
      between the two groups were not different. Endoscopic saphenous vein harvest is
      associated with a reduced incidence of serious wound complications and, in
      selected patients, shortened postoperative hospital stay.

PMID- 11221937
TI  - Design of endovascular grafts for abdominal aortic aneurysm repair.

PMID- 11221938
TI  - Surgery for carotid artery stenosis following neck irradiation.
AB  - Carotid angioplasty and stenting (CAS) is being promoted for patients with
      carotid artery stenosis who have received neck irradiation. We reviewed our
      experience with carotid endarterectomy (CEA) following neck irradiation to
      determine if indeed postoperative and long-term problems were an issue in these
      patients. Over the past 13 years, 10 patients with a history of neck irradiation
      underwent 11 procedures. The average time interval between radiation treatment
      and surgery was 14 years (range 1-44). All carotid arteries were repaired with a
      standard endarterectomy, eight of which were patched. Three patients had
      undergone a radical neck dissection on the side ipsilateral to the carotid
      lesion. They received a pectoral myocutaneous flap (PMF) to protect the carotid
      artery and optimize wound healing. The lack of perioperative complications and of
      morbidity indicate that carotid reconstruction for patients with previous neck
      irradiation is safe and durable. Until long-term favorable results with CAS are
      available for these patients, operative intervention should remain the standard
      treatment.

PMID- 11221939
TI  - Causes of perioperative stroke after carotid endarterectomy: special
      considerations in symptomatic patients.
AB  - In order to maximize the efficacy of carotid endarterectomy (CEA), the rate of
      perioperative stroke must be kept to a minimum. A recent analysis of carotid
      surgery at our institution found that most perioperative strokes were due to
      technical errors resulting in thrombosis or embolization. From 1992 through 1997
      we have performed nearly 1200 additional CEAs; the purpose of this study was to
      examine recent trends in the causes of perioperative stroke, with specific
      attention to differences in symptomatic and asymptomatic patients. The records of
      1041 patients undergoing 1165 CEAs were reviewed from a prospectively compiled
      database. Analysis of these data showed that a history of preoperative stroke
      appears to increase the risk of perioperative stroke after CEA. Surgical factors
      associated with perioperative stroke include an inability to tolerate clamping,
      use of an intraarterial shunt, and having surgery performed under general
      anesthesia; these factors are clearly interrelated and only the use of
      intraarterial shunting remains a risk factor by multivariate analysis. Over half
      of all perioperative strokes (54%) appear to be caused by intraoperative or
      postoperative thrombosis and embolization. The patient requiring use of
      intraarterial shunting and/or with a preoperative stroke most likely has a
      significant watershed area of brain at increased risk of infarction. However,
      technical errors are still the most common cause of perioperative stroke in these
      high-risk patients. Such high-risk patients may manifest clinical stroke from
      small emboli that may be tolerated by asymptomatic clamp-tolerant patients.
      Technical precision and appropriate cerebral protection are particularly critical
      for successful outcomes in high-risk patients.

PMID- 11221940
TI  - Vertical ramus osteotomy allows exposure of the distal internal carotid artery to
      the base of the skull.
AB  - Exposure of the distal internal carotid artery (ICA) above the level of the
      second cervical vertebra can be difficult and often require maneuvers such as
      division of the digastric muscle or mandibular subluxation. These techniques
      increase exposure but may not provide adequate access. We report a series of
      eight cases in which vertical division of the mandibular ramus provided access of
      the ICA up to the base of the skull. Over the last 10 years, eight patients
      underwent vertical ramus osteotomy (VRO) to aid in distal ICA exposure.
      Preoperative arteriography revealed ICA lesions within 1.5 cm of the skull base.
      Indications for surgery were compelling and included gunshot wounds to zone III
      of the neck (n = 2), transient ischemic attack (n = 2), and preocclusive stenosis
      (n = 4). VRO was performed through a standard vertical neck incision and was
      created from the depth of the sigmoid notch to the angle of the mandible after
      elevating the masseter muscle from the bone. Miniature titanium plates were used
      to reapproximate the mandible after endarterectomy (n = 5), bypass (n = 2), or
      arterial repair (n = 1). We found that VRO provides reliable exposure of the
      distal ICA up to the base of the skull. Unlike mandibular subluxation, it
      requires no pre-incision preparation, thus mandibulotomy can be performed after
      carotid artery dissection has begun, and may even be avoided. VRO is especially
      useful when carotid artery pathology unexpectedly extends beyond the usual field
      of exposure. Work on the carotid artery at the skull base is associated with
      significant complications and should be reserved for compelling indications.

PMID- 11221941
TI  - Long-term follow-up and patient satisfaction after surgery for thoracic outlet
      syndrome.
AB  - The purpose of this study was to review the long-term outcomes, particularly
      patient satisfaction, of patients surgically treated for thoracic outlet syndrome
      (TOS). All patients who had undergone surgery for TOS at the University of Iowa
      Hospitals and Clinics between 1988 and 1999 were reviewed. A retrospective chart
      review of 29 patients (36 operations) was performed. In addition, 20 (69%) of the
      patients were able to be contacted for a phone survey. There was no operative
      mortality. Specific neurologic complications occurred in 4/36 operations (11%)
      including one brachial plexus traction palsy, two phrenic nerve palsies, and one
      long thoracic nerve palsy. All nerve palsies were either mild or temporary. Mean
      follow-up was 4 years. On phone survey, 80% of the patients were actively
      employed. Twenty-seven percent reported that they had an excellent result, 58%
      reported they had a good result, 8% reported that they had a fair result, and 8%
      had a poor result. If they had it to do over again, 85% of the patients would
      have the same surgery again for relief of TOS.

PMID- 11221942
TI  - Safety and efficacy of early surgical decompression of the thoracic outlet for
      Paget-Schroetter syndrome.
AB  - The surgical treatment of Paget-Schroetter syndrome has evolved to include early
      thrombolytic therapy and an interval period of anticoagulation, followed by late
      surgical decompression of the thoracic outlet. More recently, we have developed
      an abbreviated course of therapy in which the thrombolytic therapy is followed by
      early surgical decompression during the same admission, then a period of
      anticoagulation. We compared early surgical decompression with the standard
      management protocol to determine safety and efficacy of the early treatment
      algorithm. Nine patients were treated with lysis and early operation. These were
      compared with the preceding nine consecutive patients treated with lysis and
      staged operation. Demographic data, risk factors, duration of thrombosis, lytic
      therapy, time to surgery, operative variables, and postoperative complications
      were analyzed. Our results showed that thrombolysis followed by early operation
      does not result in increased perioperative morbidity or mortality. Early surgical
      decompression of the thoracic outlet during the same admission as lysis is as
      safe and efficacious as the traditional (staged decompression) approach to Paget
      Schroetter syndrome. Lysis followed by early surgical decompression should be
      considered a new standard of care in the management of Paget-Schroetter syndrome.

PMID- 11221943
TI  - Determinates of functional disability after complex upper extremity trauma.
AB  - This is a retrospective chart review of 71 patients who were operated on for
      presumed upper extremity arterial trauma between June 1992 and June 1998.
      Penetrating trauma occurred in 50 (70%) patients, and blunt trauma in 21 (30%).
      There were 2 innominate, 6 subclavian, 13 axillary, 26 brachial, 5 radial, 6
      ulnar, and 6 multiple arterial injuries. There were 7 negative explorations (4
      venous injuries, 2 false-positive angiograms, and 1 branch artery injury). In
      addition to the vascular injury, 44 patients (69%) had another injury in the
      extremity, including 8 (12.5%) orthopedic injuries, 12 (19%) nerve injuries, and
      24 (37.5%) combination nerve and orthopedic injuries. There were three arterial
      thromboses, one arterial disruption, and four amputations, resulting in a patency
      rate and limb salvage rate of 94%. Persistent disability was more common in those
      patients with blunt injury (p = 0.02) and in those patients with associated
      neurologic and orthopedic injuries (p < 0.05). Full functional recovery was seen
      in 21 (33%) patients, while some form of disability was noted in the remaining
      67%. The magnitude of the concomitant neurologic injury was the major determinate
      of functional outcome in this patient population.

PMID- 11221944
TI  - Left atrial femoral bypass and cerebrospinal fluid drainage decreases neurologic
      complications in repair of descending and thoracoabdominal aortic aneurysms.
AB  - This study was undertaken to evaluate the role of cerebrospinal fluid (CSF)
      drainage and left atrial to femoral artery (LAFA) bypass in preventing
      postoperative neurologic complications for patients who had undergone descending
      and thoracoabdominal aortic aneurysm (TAAA) repair. LAFA bypass and CSF drainage
      were used as adjuncts in the treatment of 8 patients with descending and 13
      patients with TAAAs (December 1999 to March 2000). LAFA bypass was established
      with the use of a centrifugal Biomedicus pump. Distal flows were maintained
      between 1.5 and 2.5 L/min during the procedures. Mean LAFA bypass time was 40
      (range, 21 to 60 min). The CSF pressure was kept below 10-12 mmHg during the
      operations and for the first 72 hr postoperatively. All patients received heparin
      (1 mg/kg), which was reversed at the completion of the procedure. Passive
      hypothermia (rectal temperature: 32 degrees-34 degrees C) was used in all cases.
      All patent T8-L1 intercostal arteries were reattached to the graft. There were 13
      men and 8 women. The median age was 56 years (range, 49 to 78). Chronic aortic
      dissection was the cause of the aneurysm in 9 patients (43%), trauma in 1 patient
      (5%), and medial degeneration in 11 patients (52%). There were four type I (19%),
      four type II (19%), and five type III (24%) TAAA. In eight patients (38%) the
      entire descending thoracic aorta was aneurysmal. Our results showed that the use
      of CSF drainage and LAFA bypass prevents paraplegia/paraparesis after repair of
      thoracoabdominal and descending thoracic aneurysms.

PMID- 11221945
TI  - Comparison of open transabdominal AAA repair with endovascular AAA repair in
      reduction of postoperative stress response.
AB  - Operative intervention causes a necessary biologic response known as the
      hypermetabolic stress response. Less invasive operative procedures may cause
      fewer metabolic and endocrine derangements. To evaluate the metabolic and
      endocrine differences between endovascular and transperitoneal abdominal aortic
      aneurysm (AAA) repair, 10 patients underwent standard open repair (open group)
      and 10 patients underwent endovascular repair of AAA (endovascular group) with a
      modular bifurcated endograft. Blood samples were obtained prior to general
      anesthesia (baseline) and every 6 hr for a 24-hr period. Assays for hormones
      related to the postoperative stress response as well as retinol-binding protein
      were performed. Peak hormonal values are presented in relation to the baseline.
      Demographic analysis of the two groups showed that there were no significant
      differences in age or ASA classification. The open group had a 9.6-fold increase
      in epinephrine release, which was significantly higher than the 1.6-fold increase
      in the endovascular group (p < 0.05). Elevations in cortisol were also
      significantly higher in the open group. Early postoperative nutritional
      derangements, as reflected by the levels of retinol-binding protein, were far
      less in the endovascular group than in the open group. Endovascular AAA repair
      appears to be associated with a marked reduction in the hypermetabolic stress
      response and nutritional deterioration, compared to traditional open repair. This
      reduction in physiologic stress may have salutary effects on the incidence of
      postoperative medical morbidity.

PMID- 11221946
TI  - Endovascular revascularization of renal artery stenosis in the solitary
      functioning kidney.
AB  - The treatment of renal artery stenosis by angioplasty and stenting is an
      effective and accepted alternative to surgery for the treatment of renovascular
      hypertension and preservation of renal function. We report the technical and
      clinical outcomes of renal artery stenting in patients with a solitary
      functioning kidney and renal artery stenosis. From October 1993 to November 1999,
      30 stents were placed in the renal arteries of 27 patients (mean age 72+/-8
      years) with a solitary functioning kidney and azotemia. The mean diameter renal
      artery stenosis was 86+/-14%. The mean preprocedure serum creatinine (Cr) level
      was 3.0+/-1.5 mg/dL (range 1.5-7.5 mg/dL), arterial blood pressure was 171+/
      29/85+/-13 mmHg, and the number of antihypertensive drugs was 2.9+/-1.1.
      Indications for stenting were suboptimal balloon dilation (n = 16), intimal
      dissection (n = 6), and restenosis following angioplasty (n = 5). Atherosclerotic
      ostial lesions were present in 25 (93%) of 27 renal arteries. This represents the
      largest series of renal artery stenting in patients with a solitary functioning
      kidney, and demonstrates this treatment modality to be a relatively safe
      alternative to conventional surgery in this high-risk patient group. Most (74%)
      of the patients in this series had improved or stabilized renal function. Further
      efforts to define preprocedural indicators of success are necessary to identify
      the patients who may benefit from revascularization of their solitary kidney.

PMID- 11221947
TI  - Combined iliac angioplasty and infrainguinal revascularization surgery are
      effective in diabetic patients with multilevel arterial disease.
AB  - The success of percutaneous transluminal angioplasty (PTA) in the treatment of
      common and external iliac atherosclerotic lesions has been established for the
      general population. However, several studies have suggested that the presence of
      diabetes may reduce the effectiveness of iliac angioplasty, particularly in the
      setting of limb-threatening ischemia requiring concomitant lower extremity
      revascularization. This study compared the results of iliac artery PTA performed
      in conjunction with infrainguinal bypass for limb-threatening ischemia for
      diabetic (DM) and nondiabetic (non-DM) patients. Between 1991 and 2000, 159 PTA
      were performed in 126 patients (DM = 99/79%, non-DM = 27/21%) in conjunction with
      subsequent infrainguinal bypass for limb-threatening ischemia (gangrene = 42%,
      ulcer = 36%, rest pain = 22%). These patients were followed prospectively using a
      computerized vascular registry. Stents were placed in 34 (21.4%) cases for
      suboptimal angioplasty results. In this study the combined use of standard
      surgical and endoluminal modalities for the treatment of multilevel arterial
      occlusive disease resulted in excellent cumulative patency and limb salvage
      rates. The presence of diabetes did not alter these favorable results. Multimodal
      vascular therapy may be used effectively in diabetic patients with limb
      threatening ischemia due to multiple levels of arterial occlusion.

PMID- 11221948
TI  - Analysis of nonpenetrating clips versus sutures for arterial venous graft
      anastomosis.
AB  - The use of nonpenetrating clips (NPC) for vascular anastomosis is quickly
      becoming accepted. Studies attest to decreased anastomotic time, comparable
      patency rates, and decreased blood loss. Few human studies on the use of NPC have
      been done to date. The purpose of this study was to evaluate primary patency
      rates, operative time, and complications associated with NPC compared to those
      with standard sutures for arterial venous graft (AVG). We retrospectively
      reviewed the clinical course of 82 patients with a mean age of 45 years (range,
      22 to 87) from February 1996 to July 1999. All patients underwent upper extremity
      AVG construction. The procedures were performed at a single institution, by a
      single, well-experienced surgeon who has extensive experience with NPC. Primary
      patency rates, operative time, and complications were analyzed. Overall
      thrombotic incidence of AVG when NPC were used (27/48, 56%) was similar to that
      of sutures (17/34, 50%). Thrombotic incidence within the first year was similar
      as well (23/48, 48% and 13/34, 38%). The mean time to primary thrombosis was
      similar in both groups (6.9 and 6.8 months). The operative time required to
      construct an AVG with NPC (83 min) was significantly less than that with sutures
      (96 min) (p = 0.015). There was no significant difference in incidence of graft
      infection or pseudoaneurysm formation. NPC for AVG reduced operative time and
      resulted in primary patency and complication rates similar to those associated
      with use of sutures. The mean time to primary thrombosis was similar for both
      groups. Our findings suggest an intimal hyperplastic response of a similar nature
      resulting in thrombosis of both NPC and sutured AVGs.

PMID- 11221949
TI  - Noninvasive localization of infrainguinal arterial occlusive disease in
      diabetics.
AB  - A retrospective review of 101 diabetics without aortoiliac disease was carried
      out to analyze the ability of various noninvasive tests to predict the level of
      significant (>50% stenosis) infrainguinal arterial disease. Patients were studied
      with anklebrachial indices (ABI), toebrachial indices (TBI), segmental pulse
      volume recordings (PVR), segmental pressures (SEGP), segmental Doppler waveforms
      (DWF), and arteriography. Results were classified as normal, disease at the
      femoropopliteal level, infrapopliteal level, or both levels (multilevel), or
      noninterpretable. Our findings for the entire study showed that, as a single
      test, DWF appears to have the best angiographic correlation, although the summed
      diagnosis of combined DWF and PVR data is superior in distinguishing multilevel
      disease from isolated tibial disease. SEGP are of very limited use in diabetics,
      even in multimodality testing, and we no longer include that test in our routine
      evaluation of diabetics.

PMID- 11221950
TI  - Outcomes with plantar bypass for limb-threatening ischemia.
AB  - Patients with severely diseased or occluded infrageniculate arteries, limited
      runoff, and tissue loss may often present for primary amputation. In this study,
      we review our experience with plantar artery revascularization when no other
      bypass options are feasible. All patients requiring infrainguinal bypass to the
      plantar artery level over the last 3 years were prospectively entered into our
      vascular surgery database. Indications, demographics, length of stay (LOS),
      outcome, and patency were reviewed. Our results showed that plantar artery bypass
      is a safe and reasonable alternative to primary amputation. Excellent limb
      salvage can be achieved if the bypass remains patent through the initial 30 days
      postoperatively.

PMID- 11221951
TI  - Revascularization and quality of life for patients with limb-threatening
      ischemia.
AB  - Traditional outcomes following revascularization for chronic critical limb
      ischemia consider limb retention and hemodynamic results. Health-related quality
      of life is not measured. This study was undertaken to determine if surgery for
      chronic critical limb ischemia improves health-related quality of life. Forty-six
      patients undergoing revascularization (anklebrachial index <0.4 for nondiabetics,
      ankle-brachial index <0.6 for diabetics and rest pain or nonhealing ischemic
      ulcers) completed pre- and postoperative Short-Form 36 questionnaires, which were
      used to assess health-related quality of life in patients undergoing arterial
      reconstruction for chronic critical limb ischemia. Patients reported a mild
      improvement in functional status postoperatively, and overall low health-related
      quality of life. Health-related quality of life is slow to show progress
      following revascularization. Health-related quality of life should become an
      important outcomes end point.

PMID- 11221952
TI  - The value and limitations of the arm cephalic and basilic vein for arteriovenous
      access.
AB  - The National Kidney Foundation has identified the use arteriovenous grafts (AVG)
      and the interventions required to maintain their patency as two major causes of
      increased expenditure in the management of hemodialysis access in end-stage renal
      disease patients. They have issued an appeal for the increased use of native
      arteriovenous fistulae (AVF). Although the radialcephalic AVF is considered to be
      the procedure of choice for these patients, other veins should be sought after to
      maintain an all-autogenous AVF policy. We examined our experience of using arm
      veins that were transposed to the brachial artery. Over the last 2.5 years, 109
      brachiocephalic AVF (BCAVF) and 63 brachiobasilic AVF (BBAVF) were placed in 163
      patients with chronic renal failure. In each group, 40 and 25 patients were
      males, respectively. Ages ranged from 29 to 88 years (mean 67+/-1.4 years) and 37
      to 84 years (mean 69+/-2.0 years) in each group. Diabetic patients comprised 56
      and 65% of each group and hypertensive patients comprised 73 and 75% of each
      group. Data collection was via chart review, personal interviews, and review of
      the dialysis records. Patency was assessed by life-table analysis. The log-rank
      test was performed in conjunction with Kaplan-Meier survival analysis. Our
      results showed that the use of BCAVF and BBAVF appears to be a viable alternative
      to prosthetic arteriovenous grafts. On the basis of our experience, an algorithm
      for placement of AVF is suggested.

PMID- 11221953
TI  - Abnormal duplex findings at the proximal anastomosis of infrainguinal bypass
      grafts: does revision enhance patency?
AB  - Using color duplex ultrasound (CDU) surveillance of autogenous infrainguinal
      bypasses, a peak systolic flow velocity (PSFV) ratio of greater than 3 to 1
      within the graft relative to adjacent PSFV has been accepted as predicting
      significant stenosis mandating revision. At the proximal anastomosis, where
      significant vessel diameter differences and turbulent flow exist, the validity of
      these criteria is less clear. Our purpose was to review our experience with
      proximal anastomotic abnormalities in a CDU surveillance protocol. Routine CDU
      surveillance for all infrainguinal bypass gratis consisted of evaluation in an
      accredited vascular laboratory at 1 month postoperatively, every 3 months for the
      first year, every 6 months in the second year, and annually thereafter. Grafts
      with a PSFV ratio of >3 at the proximal anastomosis on any CDU study were
      included in this review. From our results we conclude that currently accepted CDU
      criteria for graft-threatening stenosis may not be valid for abnormalities at the
      proximal anastomosis of infrainguinal grafts. Regression of these abnormalities
      is common. Better CDU criteria are needed for predicting not only severity of
      proximal anastomotic stenosis but also likelihood of graft thrombosis.

PMID- 11221954
TI  - Use of 5-FU plus hyperbaric oxygen for treating malignant tumors: evaluation of
      antitumor effect and measurement of 5-FU in individual organs.
AB  - PURPOSE: Hyperbaric oxygen (HBO) has been shown to increase tumor
      radiosensitivity. Several reports indicate that it also increases sensitivity to
      alkylating agents, but other reports suggest that it may speed angiogenesis and
      tumor growth. To throw light on these questions, we investigated the effects of
      HBO and 5-fluorouracil (5-FU), individually and in combination, on Sarcoma 180
      implants in mice. METHODS: We administered 5-FU at a dose of 0.75 mg/mouse six
      times per week and HBO at 2 atm absolute pressure for 90 min six times per week,
      both 17 times in total. In combination treatment, HBO was administered
      immediately after 5-FU injection. RESULTS: Over the treatment period, tumor
      diameter increased 277.8% in the untreated control group, 244.1% in the group
      receiving HBO monotherapy, 182.7% in the group receiving 5-FU monotherapy, and
      138.5% in the group receiving combination therapy. Concomitant HBO increased
      accumulation of 5-FU in the tumors, liver, and kidneys, but not in the brain, of
      recipient animals. CONCLUSIONS: Based on the above results, we conclude that
      concomitant HBO enhances the effects of 5-FU.

PMID- 11221955
TI  - Pharmacokinetics of liposomal daunorubicin (DaunoXome) during a phase I-II study
      in children with relapsed acute lymphoblastic leukaemia.
AB  - PURPOSE: The pharmacokinetics of DaunoXome were studied during a multicentric
      phase I-II study performed in children suffering from relapsed acute
      lymphoblastic leukaemia and treated on a weekly schedule. PATIENTS AND METHODS: A
      group of 18 patients were studied during the first course of treatment at dose
      levels between 40 and 120 mg/m2. Blood samples were obtained up to 72 h after
      infusion. The liposomal and free forms of daunorubicin, as well as
      daunorubicinol, were separated and quantified by HPLC using fluorometric
      detection, and data were analysed using a model-independent approach. RESULTS:
      Unchanged liposomal daunorubicin disappeared from plasma following a
      monoexponential decay. Its AUC represented 95.8% of the total fluorescent species
      found in plasma and increased linearly with the dose administered. The
      elimination half-life was 5.23 h, total plasma clearance 0.344 1/h per m2, and
      volume of distribution at steady state 2.08 l/m2. Free daunorubicin and
      daunorubicinol were detected in plasma at all time-points studied. Their AUCs
      represented, respectively, 2.53% and 1.70% of total fluorescent species and their
      elimination half-lives were, respectively, 16.6 h and 22.3 h. The
      daunorubicinol/daunorubicin AUC ratio was 0.82%. CONCLUSIONS: This study is the
      first to demonstrate that free daunorubicin is present in plasma after DaunoXome
      administration and that it originates from in vivo release from the liposomes.
      The pharmacokinetics of free daunorubicin appeared to be comparable to those
      observed after conventional administration. However, the concentration of
      daunorubicinol appeared to be lower than that found after conventional
      administration of daunorubicin.

PMID- 11221956
TI  - A review of dose-limiting events in phase I trials: antimetabolites show
      unpredictable relationships between dose and toxicity.
AB  - INTRODUCTION: In a sample of NCIC CTG phase I trials we noted that studies of
      antimetabolites were frequently confounded by the occurrence of dose-limiting
      toxicities (DLT) at doses well below those ultimately recommended (recommended
      dose, RD) for further study, necessitating frequent expansion of dose levels and
      usually a change to more conservative dose escalation. This slowed development,
      exposed patients to ineffective doses of drugs, and raises concerns about the
      safety of current trial designs which include a single patient per dose level.
      Conversely, some patients treated at the RD may be receiving inadequate doses of
      anticancer drugs. To determine if this was a general phenomenon, we undertook a
      review of the results of a large group of phase I trials of cytotoxic agents.
      METHODS: Starting dose (SD), number of dose levels, dose at first DLT (D-DLT),
      maximum tolerated doses (MTD, dose at which DLT is seen in two or more patients)
      and RD were extracted from the NCI-Canada phase I trial database, and from a
      literature survey of phase I studies published between 1985 and 1999. Combination
      phase I and phase Ib studies were excluded. RESULTS: The review included 33
      trials with antimetabolites and 60 with other cytotoxic agents. The median ratio
      D-DLT/MTD was 0.33 for antimetabolites and 0.75 for other cytotoxic agents (P <
      0.01). Similarly, the median ratio D-DLT/RD was 0.43 for antimetabolites and 1
      for other cytotoxic agents (P < 0.01). The median number of dose levels tested
      was nine for antimetabolites and six for other cytotoxic agents. DISCUSSION:
      Statistically significant differences in the ratios D-DLT/MTD and D-DLT/RD
      between antimetabolites and other cytotoxic compounds were noted, confirming our
      initial observations that unpredictable DLT occurs earlier and at lower dose
      levels in phase I clinical trials of antimetabolites than would be expected as
      compared to other classes ofcytotoxic agents. Toxicity thus appears to be
      incompletely predicted by dose alone for antimetabolites. DLT may occur in
      certain patients at doses well below the RD. Current phase I design may not be
      ideal for development of these compounds, and should focus on pharmacodynamic
      endpoints in addition to traditional pharmacokinetic and clinical endpoints.

PMID- 11221957
TI  - The platelet-sparing effect of paclitaxel is not related to changes in the
      pharmacokinetics of carboplatin.
AB  - PURPOSE: To determine whether the platelet-sparing effect of paclitaxel is
      related to changes in pharmacology of carboplatin. METHODS: A group of 32
      patients with epithelial ovarian cancer were treated with intraperitoneal (i.p.)
      carboplatin-based chemotherapy with carboplatin alone or in combination with
      cyclophosphamide or paclitaxel, and the relationship between the pharmacology of
      serum platinum and thrombocytopenia was examined. The target AUC of i.p.
      carboplatin was 6.5 mg min/ml. Cyclophosphamide was administered intravenously at
      400 mg/m2 after i.p. carboplatin and paclitaxel at 175 mg/m2 was given before
      i.p. carboplatin. RESULTS: Ten patients received i.p. carboplatin alone, 10
      received cyclophosphamide and 12 received paclitaxel. The ages of the patients,
      body surface area, serum creatinine, platelet count before chemotherapy, and the
      total dose of carboplatin in each patient were similar in all groups. The
      measured AUC, Cmax, T 1/2, and MRT were similar in these groups. The nadir
      platelet counts were significantly higher (P = 0.0018) in patients treated with
      i.p. carboplatin with paclitaxel (12.1 +/- 4.3 x 10(4)/mm3) compared with
      carboplatin alone (5.2 +/- 3.3 x 10(4)/mm3) or with cyclophosphamide (5.2 +/- 4.8
      x 10(4)/mm3). The percentage decrease in platelet counts was significantly lower
      (62.5 +/- 18.2%) in patients treated with paclitaxel than in the other two groups
      (81.5 +/- 12.6% carboplatin alone, 88.7 +/- 7.9% with cyclophosphamide).
      CONCLUSION: The addition of paclitaxel or cyclophosphamide to i.p. carboplatin
      did not alter the pharmacology of serum platinum. Thrombocytopenia was
      significantly less in patients treated with carboplatin in combination with
      paclitaxel. The platelet-sparing effect of paclitaxel is not related to changes
      in the pharmacology of carboplatin.

PMID- 11221958
TI  - The absorption of retinoic acids from the gastrointestinal tract is dependent
      upon chemical structure.
AB  - PURPOSE: The gastrointestinal permeability of a number of retinoic acids was
      determined in order to evaluate whether the gastrointestinal membrane was able to
      distinguish between retinoids in which the polyene chain was present in several
      different isomeric forms. In addition, the structure of the six-membered ring was
      varied in order to determine which portion of the molecule was most important for
      its recognition by the membrane. The role of bile salt micelle composition in the
      intestinal absorption of retinoids was also evaluated. METHODS: In situ perfused
      rat intestinal segment preparations (= 78) were used, and the retinoids were each
      perfused at a concentration of approximately 1 microg/ml in either simple
      micelles of sodium taurocholate (10 mM) or mixed micelles of sodium
      taurocholate/egg phosphatidylcholine (10 mM/10 mM). The flow rate of the
      perfusate was either 0.1 or 0.35 ml/min. RESULTS: For each retinoid, the mixed
      micelles were associated with a higher degree of retinoid uptake into the jejunal
      cells than were the simple micelles. In addition, the permeability was higher
      when the perfusate flow was greater, indicating that the aqueous boundary layer
      of the intestine contributes to the resistance to the disappearance of the
      retinoid from the intestinal lumen. Retinoid structure was also found to have a
      significant effect on the permeability in the mixed micelle systems at both low
      and high flow rates, but not with simple micelles. The structure of the six
      membered ring was not a major determinant of the permeability. However, the
      permeability of the retinoids with the polyene chain in the 13-cis position was
      significantly greater than when the chain was all-trans or in the 9-cis position.
      CONCLUSIONS: The isomeric position of the polyene chain and the presence of
      phospholipid in the micellar vehicle have a significant influence on the membrane
      transport of the retinoic acids.

PMID- 11221959
TI  - Suppression of tumor growth and metastasis by dietary fish oil combined with
      vitamins E and C and cisplatin.
AB  - PURPOSE: The anticancer activity of omega-3 polyunsaturated fatty acids (omega-3
      PUFA) has been shown in a large number of studies. This study was undertaken to
      analyze the combined effect of omega-3 PUFA and antioxidative vitamins on the
      level of spontaneous metastatic dissemination. The supportive effect of this
      dietary combination on chemotherapy with cisplatin (CP) was determined in
      parallel. METHODS: C57BL/6J mice bearing the Lewis lung carcinoma 3LL were fed ad
      libitum one of three isocaloric diets containing 5% soybean oil supplemented with
      40 mg/kg alpha-tocopherol acetate (SO diet), or 4% fish oil plus 1% corn oil, and
      basal amounts of vitamin E (FO diet) or FO diet supplemented with vitamins E and
      C (FO+E+C diet). These diets were tested in combination with the conventional
      cytotoxic agent CP in a series of regimens. Tumor growth, feed consumption, body
      weight, lung metastasis and lung histology were followed. RESULTS: Both the FO
      dietary groups showed significantly lower tumor development than the SO group in
      all examined parameters, indicating that omega-3 PUFA have anticancer activity.
      However, the FO diet, in comparison with the FO+E+C diet induced a significantly
      slower rate of tumor growth, and lower metastatic load, as reflected in lung
      weight. The decrease in the anticancer activity of FO by the addition of vitamins
      E and C suggests that in situ oxidation of omega-3 PUFA underlies their
      anticancer action. It is thus proposed that oxidized omega-3 PUFA accumulates in
      the membranes and the cytosol of tumor cells, reducing their vitality and
      eventually leading to their death. No signs of anorexia or cachexia were observed
      in either FO group, in contrast to the SO group. CP treatment with the SO diet
      had no apparent therapeutic effect, while with the FO diets it reduced the
      metastatic load. The best regimen of this combined treatment was FO diet followed
      by CP treatment with FO diet supplemented with vitamins E and C after resection
      of the primary growth. This regimen could be translated to a combined therapy for
      human cancer. CONCLUSIONS: Diets enriched with omega-3 PUFA may have beneficial
      anticancer effects in particular when containing only basal amounts of
      antioxidants such as vitamin E or C. Furthermore, the addition of drugs which
      promote oxidation of omega-3 PUFA, such as ferrous salts (e.g. as prescribed for
      the treatment of anemia), may further increase these effects. However, the
      supportive effect of omega-3 PUFA in chemotherapy (e.g. with CP) increases when
      vitamins E and C are also included.

PMID- 11221960
TI  - Plasma pharmacokinetics and cerebrospinal fluid penetration of hypericin in
      nonhuman primates.
AB  - Hypericin, a polycyclic aromatic dianthroquinone, is a natural pigment derived
      from the plant Hypericum perforatum (St John's Wort). The compound has been
      synthesized and shown to inhibit the growth of malignant glioma cell lines in
      vitro via inhibition of protein kinase C. Oral hypericin has entered clinical
      trials in adults with recurrent malignant glioma. PURPOSE: The present study was
      performed to characterize the plasma pharmacokinetics (PK) and cerebrospinal
      fluid (CSF) penetration of hypericin in nonhuman primates. METHODS: Hypericin was
      administered as an intravenous bolus dose of 2 mg/kg (n = 3) or 5 mg/kg (n = 1).
      Plasma and CSF (ventricular or lumbar) were sampled prior to administration and
      at frequent intervals for up to 50 h after administration of the drug. Hypericin
      concentrations in plasma and CSF were determined using a specific reverse-phase
      HPLC assay. RESULTS: Mean peak plasma concentration of hypericin following the 2
      mg/kg dose was 142 +/- 45 microM. Elimination of hypericin from plasma was
      biexponential, with an average alpha half-life of 2.8 +/- 0.3 h and average
      terminal half-life of 26 +/- 14 h. CONCLUSIONS: The 2 mg/kg dose in the nonhuman
      primate was sufficient to maintain plasma concentrations above 10 microM (the in
      vitro concentration required for growth inhibition of human glioma cell lines)
      for up to 12 h. No hypericin was detected in the CSF of any animal (lower limit
      of detection 0.1 microM); the CSF penetration is therefore less than 1%. A severe
      dose-limiting photosensitivity skin rash was seen at the 5 mg/kg dose level.

PMID- 11221961
TI  - The pharmacokinetics and pharmacodynamics of high-dose paclitaxel monotherapy
      (825 mg/m2 continuous infusion over 24 h) with hematopoietic support in women
      with metastatic breast cancer.
AB  - PURPOSE: We evaluated the pharmacokinetics and pharmacodynamics of high-dose
      paclitaxel (HDP) monotherapy (825 mg/m2 continuous infusion over 24 h) with
      peripheral blood progenitor cell (PBPC) and G-CSF support in 17 women with
      metastatic breast cancer. METHODS: Pharmacokinetic and pharmacodynamic data were
      collected in 17 women entered in a phase II trial of sequential HDP, and high
      dose melphalan and cyclophosphamide/thiotepa/carboplatin. RESULTS: The maximal
      plasma concentration (Cmax), area under the plasma concentration time curve
      (AUC), apparent clearance (Clapp), duration of plasma concentration above 0.05
      microM (t > 0.05 microM) for paclitaxel were (means SD): 9.11 +/- 7.45 microM,
      145 +/- 88 microM x h, 8.06 +/- 2.90 l/h per m2 and 82.4 +/- 31.2 h,
      respectively. There was a significant correlation between the plasma paclitaxel
      concentration at 1 h (r2 = 0.87), 12 h (r2 = 0.85) and 23 h (r2 =0.92) and the
      AUC (P < 0.0001). Duration of neutropenia was brief (median 3 days, range 0-5
      days) and neutrophil recovery occurred earlier (median 6 days, range 0-7 days)
      than could be attributed to infused PBPC. Median nadir count for platelets was 66
      x 10(9)/l (range 13-160 x 10(9)/l). Pharmacodynamic analysis showed no
      correlation between pharmacokinetic parameters (Cmax, AUC, t > 0.05 microM) and
      time to neutropenic nadir, duration of neutropenia, platelet count nadir and
      grades of neuropathy or mucositis. In ten patients in whom detailed neurologic
      and nerve conduction studies were performed, linear regression analysis showed a
      significant correlation between pre- and post-HDP treatment total neuropathy
      scores (r2 = 0.46, P = 0.03). CONCLUSIONS: HDP (825 mg/m2 continuous infusion
      over 24 h) did not appear to be myeloablative. The degree of neurotoxicity
      subsequent to HDP was associated with the degree of baseline neuropathy but was
      not predictable from pharmacokinetic parameters.

PMID- 11221962
TI  - Differences in intracellular sites of action of Adriamycin in neoplastic and
      normal differentiated cells.
AB  - PURPOSE: This study was performed to clarify the intracellular specificity of the
      differential cytotoxic effects of Adriamycin (ADM) on neoplastic and normal
      cells. METHODS: The mouse lymphocytic leukemia cell line L1210 and pig kidney
      proximal tubular epithelial cell line LLC-PK1 were used as neoplastic and normal
      cells, respectively. These cells were treated with various concentrations of ADM
      for 24 h and toxicological parameters were determined. RESULTS: ADM (0.1-10
      microM) significantly down-regulated cell growth rate and [3H]thymidine
      incorporation into DNA in the log phase, and at concentrations of more than 1
      microM reduced the viability of both cell lines. Lipid peroxidation was increased
      at 1 microM ADM in L1210 cells and at 10 microM ADM in LLC-PK1 cells. The
      microsomal and nuclear fractions of both cell lines showed approximately the same
      level of ADM-induced superoxide anion (O2-) production, while the mitochondrial
      fraction of differentiated LLC-PK1 cells produced the highest levels of O2-.
      Differentiated LLC-PK1 cells showed the highest mitochondrial NADH-cytochrome c
      reductase activity. L1210 cells showed lower mitochondrial activities of enzymes
      involved in scavenging of reactive oxygen species, such as superoxide dismutase,
      glutathione peroxidase and catalase, than the other cells. CONCLUSIONS: These
      results suggest that ADM exerts cytostatic effects on neoplastic and normal
      undifferentiated cells through the inhibition of DNA synthesis by DNA
      intercalation, and cytotoxic effects on neoplastic cells through the accumulation
      of reactive oxygen species resulting from low scavenger enzyme activities. The
      cytotoxic effects on normal differentiated cells may be related to the high
      levels of production of reactive oxygen species due to high mitochondrial NADH
      cytochrome c reductase activity.

PMID- 11221963
TI  - Docetaxel monotherapy in heavily pretreated metastatic breast cancer: a
      multicenter, community-based feasibility trial.
AB  - PURPOSE: To evaluate the efficacy and safety of docetaxel in heavily pretreated
      and anthracycline-resistant patients with metastatic breast cancer in an
      outpatient setting. PATIENTS AND METHODS: Between February 1996 and June 1998, 98
      consecutive patients who had progressed during or relapsed following prior
      anthracycline-containing chemotherapy were enrolled into the trial. Docetaxel was
      administered at a dose of 100 mg/m2 by intravenous infusion every 3 weeks. The
      administration of colony-stimulating factors was at the discretion of the
      attending physician. Premedication with dexamethasone was mandatory for all
      patients. RESULTS: Of the 98 patients, 93 were evaluable for toxicity and
      response. Patients had received two palliative regimens (median, range 1-5) prior
      to docetaxel treatment. The most frequent toxicity observed was leukopenia grade
      III and IV (WHO grading system) which occurred in 47% of patients (grade IV only
      in 14%). Except for alopecia grade III (64% of patients), nonhematologic side
      effects grade III-IV were rare (1-7% of patients) and included nausea,
      stomatitis, diarrhea, peripheral neuropathy, fluid retention and pulmonary
      toxicities. There were no treatment-related deaths. Objective responses occurred
      in 40% of patients (CR 6%, PR 34%), and stable disease in 38% of patients. The
      median duration of response was 5.3 months (range 0.7-18.1 months) while the
      median survival was 15 months (range 2 36 months). CONCLUSION: Docetaxel is a
      highly active agent in patients with anthracycline-resistant metastatic breast
      cancer, even in heavily pretreated patients, with moderate toxicity.

PMID- 11221964
TI  - Inactivation of O6-alkylguanine-DNA alkyltransferase by 8-substituted O6
      benzylguanine analogs in mice.
AB  - PURPOSE: The purpose of this study was to determine the usefulness of various 8
      substituted O6-benzylguanine (BG) analogs as modulators of the DNA repair
      protein. O6-alkylguanine-DNA alkyltransferase (AGT). More specifically, the
      degree of inactivation of AGT in mouse brain, liver, kidney and tumor by O6
      benzyl-8-oxoguanine (8-oxoBG), 8-aza-O6-benzylguanine (8-azaBG), O6-benzyl-8
      bromoguanine (8-bromoBG) and O6-benzyl-8-trifluoromethylguanine (8-tfmBG) was
      compared to inactivation by BG, a modulator in phase II clinical trials. BG is
      converted rapidly to 8-oxoBG in rodents, monkeys and humans. It was reasoned that
      8-substituted analogs of BG would exhibit different pharmacological properties
      compared to BG which could influence tissue bioavailability and, thus, the extent
      of AGT inactivation in vivo. We compared the tissue distribution of these agents
      and AGT activity following administration of the 8-substituted analogs. MATERIALS
      AND METHODS: At various time points up to 24 h after i.p. administration of the
      BG analogs, tissues (i.e. brain, liver, kidney), A549 lung tumor xenografts
      (i.p.) or D456 brain tumor xenografts (i.c.) were harvested from athymic nude
      mice for AGT analysis. AGT activity was quantified in tissue extracts using a
      biochemical assay with [3H]methylated DNA as a substrate. In addition,
      concentrations of BG and 8-oxoBG were determined by HPLC with fluorescence
      detection in mouse tissues following administration of drug. RESULTS: Each of the
      8-substituted analogs of BG demonstrated variable AGT inactivation capabilities
      that were comparable to or better than those of BG especially in kidney and brain
      tissues. There was a more pronounced depletion of AGT inactivation in brain and
      D456 brain tumor xenografts following administration of BG compared to 8-oxoBG
      that could be explained by a much greater concentration of AGT-inactivating drug
      (BG plus the metabolite 8-oxoBG for mice treated with BG versus 8-oxoBG for mice
      treated with 8-oxoBG) present in these tissues. The AUCs for brain, kidney and
      liver were 3.2, 6.9 and 1 1.8 times greater for BG than for 8-oxoBG. CONCLUSIONS:
      8-substituted analogs of BG possess unique AGT-inactivation profiles in vivo that
      are different from that of BG. The AGT-inhibitory activities of BG and its major
      metabolite, 8-oxoBG, are related to tissue disposition of both drugs.

PMID- 11221965
TI  - Dose schedule of recombinant murine thrombopoietin prior to myelosuppressive and
      myeloablative therapy in mice.
AB  - PURPOSE: Thrombopoietin is being investigated as a therapeutic agent for platelet
      recovery following myelosuppressive therapy. Little information is available,
      however, on the optimal dose of this drug or the timing of its administration. To
      develop these data, a series of studies were conducted to examine the effects
      that time of dosing has on the efficacy and safety of recombinant full-length
      murine thrombopoietin in murine myelosuppression and murine myeloablation models.
      METHODS: For the myelosuppression model, mice were exposed to 500 rad whole-body
      irradiation in a cesium irradiator and received an intraperitoneal dose of 1.2 mg
      carboplatin at time 0. For the myeloablation model, mice were exposed to 900 to
      950 rad of whole-body irradiation at time 0. RESULTS: Significant increases in
      the number of platelets and red and white blood cells were observed by day 10 in
      mice that had received a single intravenous bolus dose of recombinant murine
      thrombopoietin from 2 h before until 4 h after myelosuppressive therapy compared
      to those had received myelosuppressive therapy alone. In the myeloablation
      studies, mice treated with 900 rad of whole-body irradiation alone had a
      mortality rate of 50% compared to 0% for mice that had received recombinant
      murine thrombopoietin 2 h prior to whole-body irradiation. When the whole-body
      irradiation dose was increased to 950 rad, the mortality rate of the control mice
      was 83% compared to 25% for mice that had received recombinant murine
      thrombopoietin 2 h prior to whole-body irradiation. Dosing with recombinant
      murine thrombopoietin 7 days prior to whole-body irradiation resulted in a
      mortality rate greater than or equal to that of control mice. CONCLUSIONS: These
      data suggest that pretreatment with thrombopoietin can dramatically affect
      recovery from myelosuppressive and myeloablative therapy. Therefore, the timing
      of thrombopoietin administration in relation to the therapy may be critical to
      the drug's safety and efficacy.

PMID- 11221966
TI  - A reexamination of PSC 833 (Valspodar) as a cytotoxic agent and in combination
      with anticancer agents.
AB  - BACKGROUND: The cyclosporins have been thought as being mainly immunosuppressive
      agents which interfere with the function of the MDR pump and thus play a role in
      resistance to drug anticancer effects. We reexamined their cytotoxicity in
      defined cell lines both as single agents and in combination with agents which may
      be of value in human malignant disease. METHODS: Cells were grown to confluence
      following inoculation at 5,000-8,000 cells/well in 96-well dishes, and growth
      patterns and death were determined by an MTT assay. Median effect analysis was
      used to look for synergy, additive effects, or antagonism between the
      cyclosporins and drugs with antitumor effects in humans. RESULTS: Cyclosporin A
      and PSC 833 were found to have cytotoxic activity at clinically achievable
      concentrations in breast, leukemia, and prostate cell lines. Synergistic or
      additive effects were demonstrated in all three prostate cell lines when PSC 833
      was combined with estramustine, etoposide, ketoconazole, suramin, or vinorelbine
      in the prostate cancer cell lines. Cell line-selective additive effects or
      synergism were also identified with bicalutamide, carboplatin, cisplatinum, cis
      retinoic acid, dexamethasone, 5-fluorouracil, liarozole, and trans-retinoic acid.
      CONLCLUSIONS: PSC 833 or cyclosporin alone or in combination with other agents
      may have an anticancer effect independently of their modulatory action on MDR.
      Several of the synergistic combinations which are not mediated by the MDR pump
      need to be tested in vivo for efficacy.

PMID- 11221967
TI  - A phase I and pharmacodynamic evaluation of polyethylene glycol-conjugated L
      asparaginase in patients with advanced solid tumors.
AB  - PURPOSE: To evaluate the in vitro activity of polyethylene glycol-conjugated L
      asparaginase (PEG-Lasparaginase) against fresh human tumor specimens, using the
      human tumor clonogenic assay (HTCA), and to perform a phase I dose-escalation
      clinical trial of PEG-L-asparaginase. The goal of the clinical study was to
      determine the toxicity and optimum biologic dose of PEG-L-asparaginase based on
      depletion of serum L-asparagine in patients with advanced solid tumors. METHODS:
      A modified method for determination of serum L-asparagine is described. PEG-L
      asparaginase was administered by intramuscular injection every 2 weeks to 28
      patients with various types of advanced solid tumor malignancies. At least 3
      patients were evaluated at each dose level: 250 IU/m2, 500 IU/m2, 1,000 IU/m2,
      1,500 IU/m2, 2,000 IU/m2. RESULTS: The in vitro HTCA studies suggested good
      antitumor activity against malignant melanoma and multiple myeloma. Serum L
      asparagine was most consistently and profoundly depleted (up to 4 weeks) in
      patients treated with 2,000 IU/m2. Patients receiving this dose level also showed
      more frequent grade 1, grade 2, and occasional grade 3 toxicities of
      fatigue/weakness, nausea/vomiting, and anorexia/ weight loss. Three patients
      developed hypersensitivity reactions, but these were not dose related. Two
      patients developed deep vein thromboses. We saw no episodes of clinical
      pancreatitis, but there were minor fluctuations of serum amylase and lipase. We
      saw no partial or complete responses in patients treated in this study, including
      11 patients with malignant melanoma. CONCLUSIONS: We conclude that PEG-L
      asparaginase is generally well tolerated in patients with advanced solid tumors,
      and a dosage of 2,000 IU/m2 by intramuscular injection every 2 weeks results in
      significant depletion of serum L-asparagine.

PMID- 11221968
TI  - Effect of hemodialysis on topotecan disposition in a patient with severe renal
      dysfunction.
AB  - The pharmacokinetics of topotecan have been extensively studied in patients with
      normal renal function and there is one study of patients with mild to moderate
      renal insufficiency. However, the effect of hemodialysis on topotecan disposition
      has not been reported. The objective of this study was to characterize the
      disposition of topotecan in a patient with severe renal insufficiency receiving
      hemodialysis. Topotecan lactone disposition was characterized in a patient on and
      off hemodialysis. The topotecan lactone clearance determined after administration
      of topotecan alone and with hemodialysis was 5.3 l/h per m(2) vs 20.1 l/h per m2
      respectively. At 30 min after the completion of hemodialysis, the topotecan
      plasma concentration obtained was greater than that measured at the end of
      hemodialysis (i.e. 8.0 ng/ml vs 4.9 ng/ml), suggesting a rebound effect. The
      topotecan terminal half-life off dialysis was 13.6 h, compared with an apparent
      half-life determined during hemodialysis of 3.0 h. These results demonstrate that
      topotecan plasma clearance while on hemodialysis increased approximately
      fourfold. Hemodialysis may be an effective systemic clearance process for
      topotecan and should be considered in selected clinical situations (e.g.
      inadvertent overdose, severe renal dysfunction).

PMID- 11221969
TI  - Heart and lung preservation for transplantation.
AB  - Since the beginning of transplantation the search for optimal means of organ
      preservation has been ongoing. One of the major causes of death early following
      heart or lung transplantation is graft failure. Factors that play a role in this
      problem include recipient and donor issues, but clearly procurement techniques
      and preservation solutions are important. This article summarizes the history,
      current clinical practice, and research devoted to heart and lung preservation
      for transplantation.

PMID- 11221970
TI  - Acute allograft failure in thoracic organ transplantation.
AB  - Thoracic organ transplantation is an effective form of treatment for end-stage
      heart and lung disease. Despite major advances in the field, transplant patients
      remain at risk for acute allograft dysfunction, a major cause of early and late
      mortality. The most common causes of allograft failure include primary graft
      failure secondary to inadequate heart and lung preservation during cold storage,
      cellular rejection, and various donor-recipient-related factors. During cold
      storage and early reperfusion, heart and lung allografts are vulnerable to
      intracellular calcium overload, acidosis, cell swelling, injury mediated by
      reactive oxygen species, and the inflammatory response. Brain death itself is
      associated with a reduction in myocardial contractility, and recipient-related
      factors such as preexisting pulmonary hypertension can lead to acute right heart
      failure and the pulmonary reimplantation response. The development of new methods
      to prevent or treat these various causes of acute graft failure could lead to a
      marked improvement in short- and long-term survival of patients undergoing
      thoracic organ transplantation.

PMID- 11221971
TI  - Mechanical support for acutely failed heart or lung grafts.
AB  - Heart and lung allograft dysfunction continues to be a problem in thoracic
      transplantation. Although medical therapy is often sufficient to restore
      allograft function, occasionally more invasive means are required. Mechanical
      assist devices, inhaled nitric oxide (iNO), and extracorporeal membrane
      oxygenation (ECMO) have been used with a modest degree of success in cases of
      refractory heart, lung, and heart-lung allograft failure. Allograft failure
      secondary to pulmonary hypertension often responds to iNO concentrations between
      5 and 70 ppm without major toxicity. More severe cases may require mechanical
      assist devices or ECMO and carry higher risks of complications such as bleeding,
      neurological injury, and death. Utilization of and weaning from these
      interventions require intensive monitoring. Randomized, prospective studies are
      not ethically feasible, but case reports and patient series indicate the
      usefulness of mechanical circulatory support, iNO, and ECMO. This review focuses
      on the indications, complications, and patient survival rates associated with
      these modalities.

PMID- 11221972
TI  - Preservation, reperfusion, and rejection in transgenic xenograft organs.
AB  - The success of transplantation has resulted in increasing demand, despite a
      continuing fall, in donor organ supply. This widening gap encourages the argument
      for animals to act as a reservoir for donor organs (xenografts). Despite genetic
      manipulation, transgenic xenograft organs are at risk of vascular rejection in
      man (delayed xenograft rejection), a process in part involving endothelial cell
      activation. It appears that ischemia-reperfusion injury also involves endothelial
      cell activation. Evidence already exists to support the suggestion that ischemia
      reperfusion injury may promote delayed xenograft rejection. The mechanisms of
      both these processes are briefly described and a case is made for optimum organ
      preservation of transgenic xenograft donor organs before clinical work is
      proposed.

PMID- 11221973
TI  - Adequate lung preservation for clinical lung transplantation: an important
      condition for satisfactory graft function.

PMID- 11221974
TI  - Contribution of inflammation to reperfusion injury.
AB  - Interrupting the flow of blood to an organ for even a relatively brief period
      disrupts multiple essential vascular homeostatic mechanisms. This results in the
      cardinal manifestations of reperfusion injury, which, at the tissue level, are
      comprised of leukocyte infiltration, thrombosis, edema, and vasoconstriction.
      Molecular mechanisms that are particularly relevant to postischemic inflammation
      and reperfusion injury include induction of adhesion receptor expression at the
      endothelial surface, alterations in the procoagulant/anticoagulant balance to
      promote accumulation of intravascular thrombus, oxidant stress that directly
      injures cells and indirectly promotes inflammatory upregulation, loss of
      protective second messenger cyclic nucleotide systems, and activation of the
      complement cascade that causes vascular injury as well as collateral damage to
      innocent bystander cells with the reperfused tissue. Understanding the
      inflammatory mechanisms that participate in reperfusion injury may lead to
      reperfusion therapies designed to improve postischemic organ function.

PMID- 11221975
TI  - Overview and future practice patterns in cardiac and pulmonary preservation.
AB  - Heart and lung transplantation have become standard therapy for many patients
      with end-stage heart and lung disease. Successful transplantation requires
      preservation of allografts until they can be implanted and reperfused. In the
      decades since the transplantation of thoracic organs became a clinical reality,
      many advances have been made in preoperative donor management, procurement, and
      preservation techniques. This article summarizes the state of the art in heart
      and lung preservation and review some of the areas of current research that may
      lead to improvements in preservation techniques in the future.

PMID- 11221976
TI  - Physical examination of the pulmonary system.
AB  - Physical examination of the pulmonary system includes inspection, auscultation,
      percussion, and palpation. By integrating these findings, it is often possible to
      diagnose and differentiate pulmonary edema, pleural effusion, pneumothorax,
      pulmonary fibrosis, and tracheal collapse. The veterinarian can use the physical
      examination optimally by initially performing examinations with those who are
      experienced with the methods and with an understanding of the relatively simple
      laws of physiology and physics governing transmission of sounds from the
      patient's lung.

PMID- 11221977
TI  - Pulmonary diagnostics.
AB  - Respiratory medicine is an underdeveloped subspecialty in veterinary medicine,
      and there are relatively few sophisticated tests that are available to the
      clinician that actually diagnose specific pulmonary disorders. Instead, most of
      the commonly available tests are most helpful if used to point the veterinarian
      in the right direction and to rule out the presence of other potentially
      confounding disorders. This article reviews the diagnostic tests that are
      available to evaluate dogs and cats with signs of respiratory disease, including
      the advantages, disadvantages, and current controversies regarding many of the
      tests used to evaluate animals with signs of pulmonary impairment.

PMID- 11221978
TI  - Lung biopsy.
AB  - There are many techniques that can be used to arrive at a diagnosis in dogs and
      cats with signs referable to the pulmonary system. Biopsy of the pulmonary
      parenchyma remains the technique of choice when a diagnosis is absolutely
      required; it is also the technique with the greatest potential for serious
      complications during and after the procedure. This potential caused most
      veterinarians to refrain from performing biopsy in the majority of their
      respiratory cases. Nevertheless, newer, sophisticated biopsy equipment and
      techniques are now available, with lower complication rates. As more
      veterinarians become comfortable with this technology, pulmonary biopsy will
      become more commonplace, and more definitive diagnosis will be obtained. This
      will benefit the client, the patient, the practitioner, and the profession.

PMID- 11221979
TI  - Surgically treatable upper respiratory disorders.
AB  - Diseases of the upper airways and trachea frequently result in inspiratory
      dyspnea, and surgery is often required to alleviate symptoms arising from these
      disorders. Although surgery alone may not effectively treat all diseases of the
      nasal cavity and sinuses, surgery allows removal of foreign bodies that cannot be
      retrieved endoscopically and may facilitate treatment of other disorders.
      Indications for surgery are discussed, and principles of surgery of the upper
      airways are reviewed.

PMID- 11221980
TI  - Tracheal collapse. Diagnosis and medical and surgical treatment.
AB  - Tracheal collapse remains a common clinical problem in middle-aged, small-breed
      dogs. Clinical signs are characteristic, and the diagnostic work-up serves to
      identify predisposing triggers of disease and to allow optimization of therapy
      for individual animals. Bronchoscopic confirmation of airway collapse aids in
      characterizing the extent of airway damage and allows collection of airway
      samples to rule out infectious or inflammatory airway disease. Once coincident
      diseases have been managed, cough suppressants are used to control signs and
      reduce chronic airway injury.

PMID- 11221981
TI  - Diagnosis and treatment of canine chronic bronchitis. Twenty years of experience.
AB  - Chronic bronchitis is a frustrating disease because the cause is rarely
      determined, the pathologic changes that accompany and define the disease are
      usually nonreversible and often progress to life-threatening disorders, and there
      is a lack of direct scientific evidence for the treatment recommendations that
      have been offered for the management of this disease in dogs. This article
      reviews the pathophysiology, clinical presentation, diagnosis, and evaluation of
      chronic bronchitis in dogs. Important diagnostic tools for use in diagnosis are
      discussed, including clinical pathology, chest radiographs, and culture and
      cytology of airway fluid samples.

PMID- 11221982
TI  - Feline asthma. Diagnosis and treatment.
AB  - Human asthma is not a curable disease, although spontaneous resolution is common
      in adult asthmatics who developed asthma in childhood. We do not know if this is
      true or not for cats with asthma. We do know that some cats may be only mildly
      and intermittently symptomatic and that others may suffer life-threatening
      illness. An important new development in our understanding of this disease is the
      occurrence of airway inflammation even when patients are symptom-free. It is
      therefore crucial that we direct our therapeutic attention toward the underlying
      chronic inflammation that causes the acute clinical signs of cough, wheeze, and
      increased respiratory effort. Client education is also critical so that our
      clients develop realistic expectations of the effectiveness of these treatments
      for their pets. A great deal still needs to be learned regarding the pathogenesis
      of feline asthma and the optimal approach(es) to treating cats with this
      sometimes debilitating and potentially fatal respiratory syndrome. There is great
      hope and anticipation that ongoing research can bring new treatments for human
      and feline asthmatics alike.

PMID- 11221983
TI  - Canine and feline pleural disease.
AB  - Diseases of the pleural space are relatively common disorders in small animal
      clinical practice. The abnormal presence of air, fluid, or tissue within the
      pleural cavity does not generally reflect disease of the pleura per se; instead,
      it represents a disorder of the airways or lung parenchyma or the development of
      a primary systemic illness. This article discusses common causes of the most
      frequently seen pleural space disorders and outlines general treatment plans that
      can be used as guidelines when treating actual clinical cases.

PMID- 11221984
TI  - Respiratory diseases of rodents and rabbits.
AB  - This article is written to provide differential diagnostic help for the
      practitioner who suspects respiratory disease in rodents or rabbits. The authors
      are laboratory animal veterinarians who work with rodents and rabbits on a herd
      health basis but also have considerable experience dealing with individual mice,
      rats, guinea pigs, hamsters, gerbils, and rabbits. The article presents
      descriptions of the presentation, pathology, treatment, and control of the
      primary respiratory pathogens of these species, along with an explanation of
      conditions that may confuse the diagnostic efforts. The article also mentions
      reported pathogens of secondary importance and provides extensive references.

PMID- 11221985
TI  - Rational antibiotic therapy for respiratory disorders in  dogs and cats.
AB  - Therapy of respiratory tract infections presents some unique challenges to the
      veterinary practitioner. These infections often involve underlying disease
      processes that have predisposed the patient to secondary bacterial infection and
      may complicate the response to therapy. Because of the diversity of microbial
      organisms that may colonize and invade the respiratory tract, treatment targeted
      at the infecting pathogens is best accomplished with bacterial culture and
      susceptibility testing. When these data are unavailable, rational antibiotic
      treatment should be based on familiarity with historical data and clinical
      experience. Optimal drug selection is based on predicted microbial
      susceptibility, drug distribution in the respiratory tract, and safety of the
      patient. Instituting the appropriate dosage regimen and duration of therapy
      maximizes the opportunity for a successful resolution of bacterial infections.

PMID- 11221986
TI  - Experimental drug therapy for respiratory disorders in dogs  and cats.
AB  - Experimental therapy in veterinary medicine is based on empiric reasoning. If a
      particular therapy is labeled experimental, it means that its effectiveness has
      not been demonstrated scientifically. Empiric therapy is experimental and is
      based on experience, not on scientific proof. The purpose of this article is to
      suggest the use of specific experimental drug therapies for certain respiratory
      disorders in dogs and cats.

PMID- 11221987
TI  - Guidance for the clinical evaluation of weight-control drugs.

PMID- 11221988
TI  - Lung cancer mortality in an urban and industrialised area of Brazil:1980-93.

PMID- 11221989
TI  - Guidelines on good publication practice.

PMID- 11221990
TI  - Autoimmunity in the pathogenesis of cardiomyopathy.

PMID- 11221991
TI  - Analysis of TCR Vbeta repertoire and cytokine gene expression in patients with
      idiopathic dilated cardiomyopathy.
AB  - Although the etiopathogenesis of idiopathic dilated cardiomyopathy (IDC) is still
      unclear, it is widely accepted that a complex interplay between viral infections
      and immune mechanisms is the basis of disease genesis. Previously, we showed that
      heart-infiltrating T cells of patients suffering from acute, fulminant Coxsackie
      virus B3+-IDC shared a preferential usage of three variable gene segments of the
      T cell receptor beta chain-(TCR-Vbeta) encoding families Vbeta3, 7 and 13.1. This
      indicated the possible presence of a superantigen-driven immune response. Here,
      we further investigated the IDC immunological scenario by analysing different
      phenotypes of heart-infiltrating cells: TCR repertoires, cytokine expression and
      presence of enterovirus-specific antigens. IDC patients who underwent heart
      transplantation at different times after the onset of heart failure were studied.
      A cardiac infiltrate of CD4+ and CD8+ T cells was present together with activated
      macrophages. Furthermore, the same Vbeta gene families, previously found to be
      skewed in hearts from fulminant cases of CVB3+-IDC, together with two additional
      Vbeta gene families, Vbeta1 and 5B, were increased. IL-1beta, IL-2, IL-6 and IFN
      gamma were expressed in the myocardium while others, like IL-4 were not. In
      conclusion, an orchestrated complex of immune mechanisms seems to be the basis of
      IDC etiopathogenesis.

PMID- 11221992
TI  - Prediction of diabetes and response to therapy in individual animals: are there
      lessons for man? Report on the JDF/Snow Mountain Meeting, 5-7 October 2000,
      Winter Park, CO, USA.

PMID- 11221993
TI  - Oral administration of insulin to neonates suppresses spontaneous and
      cyclophosphamide induced diabetes in the NOD mouse.
AB  - Oral administration of autoantigens to adult mice is an effective means of
      suppressing experimental autoimmune diseases including diabetes and experimental
      allergic encephalomyelitis (EAE). Different mechanisms are involved in induction
      of oral tolerance including active suppression, anergy and deletion. Oral
      tolerance is generally not inducible in the neonatal period and we previously
      found that EAE development in Lewis rats is enhanced when animals are fed myelin
      antigens as neonates. Here we report the unexpected finding that oral
      administration of either human insulin or the insulin B-chain peptide (10-24) in
      the neonatal period suppresses the development of diabetes in the non-obese
      diabetic (NOD) mouse. Furthermore, suppression of diabetes by neonatal oral human
      insulin was more effective than oral human insulin given to NOD mice (3-4 weeks
      of age). No protection against EAE was observed in NOD mice neonatally fed PLP
      (48-70) or MOG (35-55) peptide prior to EAE induction, whereas adult NOD mice
      orally tolerized to these peptides were protected against EAE. Neonatal
      administration of insulin B-chain peptide also suppressed cyclophosphamide
      induced diabetes in the NOD whereas oral insulin administration to 4-week-old NOD
      mice had no effect, suggesting that the mechanism of disease suppression in the
      neonate involved anergy or deletion. Our findings that neonatal feeding of human
      insulin or insulin B-chain peptide is effective in inhibiting diabetes when given
      to the NOD mouse may have applications in preventing diabetes in high risk human
      populations.

PMID- 11221994
TI  - Production of experimental autoimmune sialadenitis in mice immunized with
      homologous salivary gland extract and Klebsiella O3 lipopolysaccharide.
AB  - An experimental murine model for autoimmune sialadenitis was produced by repeated
      immunization of homologous salivary gland extract together with Klebsiella O3
      lipopolysaccharides as an immunological adjuvant. The cell infiltration was
      observed in the salivary glands of mice immunized more than twice. Inflammatory
      cells consisting mainly of CD4+ T cells and CD8+ T cells accumulated at the
      perivascular regions. There was hyperplasia and enlargement of ductal epithelial
      cells in the secretory acinar units in salivary glands of repeatedly immunized
      mice. The repeated immunization developed delayed-type hypersensitivity and
      autoantibody production to the homologous salivary gland extract. The
      immunohistochemical analysis showed positive staining on the cuboidal cells in
      the intercalated ducts, and the columnar pseudostratified cells in the striated
      ducts. Organ-specific antigens with molecular weights ranging from 20 to 90 kDa
      were recognized by the sera from immunized mice. Therefore, it was suggested that
      the sialadenitis was produced by the autoimmune mechanism and might be a new
      experimental model for characterization of the pathogenesis of autoimmune
      sialadenitis.

PMID- 11221995
TI  - Characteristics of inflammatory cells in spontaneous autoimmune thyroiditis of
      NOD.H-2h4 mice.
AB  - Thyroid lesions develop in most NOD.H-2h4 mice 6 weeks after they are given 0.05%
      NaI in drinking water. B cells are required for spontaneous autoimmune
      thyroiditis (SAT) development, and anti-thyroglobulin autoantibody levels
      correlate with SAT severity. Immunohistochemical staining of thyroids obtained 2
      10 weeks after administration of NaI water suggested that CD4+ T cells initially
      infiltrated the thryoid, followed by CD8+ T cells and B cells. Intrathyroidal
      CD4+ T cells are more numerous than CD8+ T cells. CD4+ T cells and B cells form
      aggregates in the thyroid, while CD8+ T cells are scattered throughout the
      thyroid. Intrathyroidal germinal centre-like structures could be observed in
      thyroid lesions with 2-3+ SAT and intrathyroidal B cells co-expressed OX40L. By
      RT-PCR, intrathyroidal expression of OX40L, OX40, CD40L, IL-2R, CTLA-4 and Igbeta
      mRNA correlated closely with the SAT severity score. These molecules were not
      expressed in normal thyroids. In the spleen, OX40L-positive cells were detected
      at 2 weeks and increased 4-6 weeks after NaI water. OX40, OX40L, CD40L, IL-2R and
      B7-1 as well as IFN-gamma and IL-4 mRNA were minimally expressed in normal
      spleens, usually began to be expressed at 2 weeks and increased to maximal level
      4-8 weeks after NaI water. These results suggest that in NOD.H-2h4 mice, the
      OX40L, OX40, CD40L and B7 molecules, which increase in the spleen and thyroid of
      these mice after receiving NaI water, may play a role in SAT development,
      implying that one or more of these molecules might be good targets for the
      prevention or treatment of SAT.

PMID- 11221996
TI  - Antidiabetogenic effect of pentoxifylline is associated with systemic and target
      tissue modulation of cytokines and nitric oxide production.
AB  - We have shown recently that xanthine derivative pentoxifylline (PTX)
      downregulates an inflammatory autoimmune process triggered in genetically
      susceptible Dark Agouti rats by multiple low doses of streptozotocin (MLD-SZ, 20
      mg/kg/day ip for 5 days). We studied the cellular and molecular consequences of
      PTX treatment during MLD-SZ-induced diabetes with special emphasis on local vs.
      systemic production of inflammatory mediators. Administration of PTX (200
      mg/kg/day for 10 days) during induction of the disease reduced clinical signs of
      diabetes and protected rats from development of destructive intrainsulitis.
      Pentoxifylline did not affect diabetogenic effect of single high dose of SZ (100
      mg/kg SZ). Ex vivo analysis of the islets of Langerhans performed in early
      disease development revealed that PTX downregulates production of proinflammatory
      cytokines IFN-gamma and TNF, as well as inducible nitric oxide synthase (iNOS)
      expression and NO production. In addition, PTX treatment suppressed splenocyte
      autoreactivity, as well as the frequency of cells expressing IL-2R and MHC class
      II antigens. There was no evidence of any changes in proportion of ICAM-1 and LFA
      1 expressing splenocytes in comparison to control MLD-SZ-treated animals. In
      contrast to suppressed intraislet production, high peripheral expression of both
      iNOS mRNA and NO was found in MLD-SZ rats treated with PTX. Taken together, the
      data indicate that the effect on both systemic and intra-islet production of NO,
      suppression of autoreactive cell activation and of local type 1 cytokine release
      may contribute to the therapeutic benefit achieved by PTX in the rat.

PMID- 11221997
TI  - Monoclonal antibodies derived from BALB/c mice immunized with apoptotic Jurkat T
      cells recognize known autoantigens.
AB  - It has been postulated that post-translational modifications and relocalization
      of proteins during apoptosis may lead to presentation of these molecules to the
      immune system in such a way that normal mechanisms of tolerance are bypassed. In
      the present study, Jurkat cells were induced to undergo apoptosis by treatment
      with the chemotherapeutic agent Ara-C. BALB/c mice were then immunized with the
      apoptotic cells and hybridomas were generated. Using an indirect
      immunofluorescence assay, the monoclonal antibodies produced were screened by
      flow cytometry for those monoclonal antibodies demonstrating reactivity with
      permeabilized apoptotic Jurkat cells but not with non-permeabilized normal or
      apoptotic Jurkat cells. Of 281 monoclonal antibodies, 20 monoclonal antibodies
      with these properties were selected for further analysis. Using 32P- or 35S
      metabolically labelled Jurkat cells, these selected monoclonal antibodies were
      screened for their ability to recognize autoantigens by immunoprecipitation and
      Western blotting. Well characterized autoimmune sera were then used to confirm
      the identity of autoantigens by immunoblotting. We demonstrate that immunization
      of normal mice with apoptotic Jurkat cells results in the formation of antibodies
      targeting multiple autoantigens or autoantigen complexes, including Ku, rRNPs,
      snRNPs and vimentin. These findings are consistent with the hypothesis that
      apoptosis can contribute to the development of autoimmunity.

PMID- 11221998
TI  - Rapid assays for detection of anti-islet autoantibodies: implications for organ
      donor screening.
AB  - The purpose of the current study was to develop and evaluate rapid assays for
      autoantibodies to GAD65 (GAA), ICA512bdc/IA-2 (ICA512AA), and insulin (microIAA,
      mIAA) as a potential tool for identification of cadaveric pancreas donors who
      were at high risk for developing diabetes. The study included 154 new onset
      diabetic, prediabetic, and healthy control subjects. Subjects were evaluated for
      all three autoantibodies in three separate assays: (1) standard (std) assay with
      a 24-h or 72-h incubation at 4 degrees C (combined GAA/ICA512AA or mIAA,
      respectively), (2) rapid assay with 1-h room temperature (RT) incubation, and (3)
      rapid assay with 2-h RT incubation. The serum samples from 777 organ donors were
      also evaluated for all three autoantibodies and all the positive samples from
      standard assay evaluated with the 1-h incubation assay. Simple linear regression
      analyses revealed excellent correlation between the standard assay and the rapid
      assays for all three autoantibodies, as follows: (1) GAA: std vs. 1 h (R2=0.85)
      and std vs. 2 h (R2=0.83), (2) ICA512AA: std vs. 1 h (R2=0.85) and std vs. 2 h
      (R2=0.84), and (3) mIAA: std vs. 1 h (R2=0.70) and std vs. 2 h (R2=0.64).
      Comparison of assay correlation rates between subject cohorts revealed no
      significant differences. Compared to their respective standard assays, the 1-h RT
      GAA assay missed 3.2% and identified an additional 1.3% of samples, the 1-h RT
      ICA512AA assay had no discordant samples, and the 1-h RT mIAA assay missed 7.1%
      and identified an additional 5.8% of samples. We analysed a series of 777 stored
      serum samples from cadaveric donors. Two of 777 (0.25%) were positive for two
      autoantibodies (both GAA and ICA512AA) and 23 of 777 (3.0%) one autoantibody (11
      IAA; 12 GAA). The rapid analysis for all three autoantibodies could be completed
      in less than 3 h with comparable concordance rates to the more time-consuming
      standard assays, making these assays an attractive option for organ donor
      screening to identify potential pancreata for immunopathogenetic research.

PMID- 11221999
TI  - Altered self-reactive antibody repertoires are a general feature of patients with
      myelodysplastic syndrome.
AB  - Myelodysplastic syndrome (MDS) is characterized by an acquired clonal disorder of
      haematopoietic progenitor cells that results in inhibition of normal
      haematopoiesis and contributes to the development of haematological malignancies.
      Autoimmune syndromes may occur in MDS, but they are not a major clinical feature
      of the disease. In the present study, we have analysed the global antibody
      repertoires of IgM and IgG in plasma of 10 patients with MDS toward self- and non
      self-antigens by quantitative immunoblotting. Myelodysplastic syndrome patients
      included in this study did not exhibit autoimmune symptoms nor secondary
      haematological neoplastic disease. Data were compared by means of multiparametric
      statistical analysis. We demonstrate that the antibody repertoires of self
      reactive IgM and IgG of patients with MDS exhibit significantly altered patterns
      of reactivity, as compared to those of healthy individuals. In contrast,
      reactivity patterns of IgM in plasma of patients and of healthy controls toward
      non-self-antigens were similar, whereas reactivity patterns of IgG of patients
      and healthy subjects toward non-self-antigens were discriminated by
      multiparametric statistical analysis. These observations indicate that a broad
      disturbance of self-recognition mechanisms is a general feature of patients with
      MDS. A failure in the regulation of self-reactivity may contribute to the
      pathogenesis of MDS.

PMID- 11222000
TI  - What's in a shape? Children represent shape variability differently than adults
      when naming objects.
AB  - Children and adults often generalize a word to objects of the same shape.
      However, the shape properties on which generalization is based are unknown. We
      investigated the degree to which two shape dimensions were represented
      categorically by children and adults when learning names for objects.
      Multidimensional scaling techniques were used to establish the perceptual
      similarity of two sets of objects in Experiment 1. In Experiments 2 and 3,
      children (from 2;8 to 4;5 years of age) and adults participated in two tasks in
      which they learned a novel name for an exemplar. We then examined how often the
      novel name was generalized to different objects and to line drawings of the
      objects. In one task, participants generalized the names from memory; in a second
      task the exemplar was in front of the participant during generalization. Adults
      accepted names more often to objects that fell "within" the proposed shape
      boundaries than to objects that fell "across" the boundaries. Children, however,
      were just as likely to generalize names to novel objects that fell within as to
      objects that crossed the boundaries.

PMID- 11222001
TI  - Does the coordination of verbal and motor information explain the development of
      counting in children?
AB  - Counting is often considered to be the coordination of two actions: saying the
      number-words and pointing to each object. We report three experiments to test the
      hypothesis that this coordination requires the use of the central executive (A.
      D. Baddeley, 1990), and that the cost of coordination decreases with age.
      Participants were 5- and 9-year-old children and adults. At all ages tested, the
      manipulation of the difficulty of each component affected counting performance
      but did not make coordination more difficult. These results suggest that, at
      least from the age 5, counting is a procedure in which the control of
      coordination is not attention demanding.

PMID- 11222002
TI  - The role of target distinctiveness in infant perseverative reaching.
AB  - From a dynamic systems perspective, perseverative errors in infancy arise from
      the interaction of the perceptual cues with the memory of previous actions. To
      evaluate this account, we tested 9-month-old infants in a task in which they
      reached for two targets. Experimenters repeatedly cued the first target, which
      always matched the background (A), and then cued the second target, which varied
      in its distinctiveness (B). We predicted that a sufficiently distinctive B target
      would lessen perseverative responding. Results showed that infants perseverated
      when reaching for two identical targets, but that they made nonperseverative
      responses when reaching in the presence of a highly distinctive B target. Reach
      direction on each trial was jointly determined by the distinctiveness of the
      target, the immediately preceding perceptual events, and the history of reaches
      in the task.

PMID- 11222003
TI  - Dissociations between featural versus conjunction-based texture processing in
      infancy: analyses of three potential contributing factors.
AB  - Many models of object perception posit that adults encode individual features in
      visual scenes before processing the conjunction relations among these features to
      generate holistic representations. Prior research suggests that infants detect
      textural discrepancies based on individual features more readily than those based
      on feature conjunctions. While these results suggest adult-like qualitative
      differences in infants' processing of features versus conjunctions, there are
      potential alternative explanations. We examined three such explanations: (1)
      failure to process one of the features that constitute the conjunction, (2)
      failure to encode and remember conjunction information that is necessary to
      detect conjunction-based textural discrepancies, and (3) the fact that
      conjunction-based discrepancies involve stimuli that are more similar to original
      stimuli than those involving feature-based discrepancies. None of these factors
      could explain 5.5-month-olds' superior processing of featural than conjunction
      based textural discrepancies. Thus, in infancy, as in adulthood, features and
      conjunction relations appear to be processed by qualitatively different
      mechanisms.

PMID- 11222004
TI  - The localization of persistent foot and mouth disease virus in the epithelial
      cells of the soft palate and pharynx.
AB  - After contact with foot and mouth disease virus (FMDV), cattle may become
      persistently infected, regardless of their pre-existing immune status or whether
      they develop clinical disease. The cellular sites of FMDV persistence have not
      previously been determined. The use of in-situ hybridization in combination with
      tyramide signal amplification (TSA) provided the first direct evidence that FMDV
      RNA is localized within the epithelial cells of the soft palate and pharynx
      during persistent infection, indicating that these cells remain persistently
      infected after contact with FMDV.

PMID- 11222005
TI  - Pathological, immunohistochemical and bacteriological findings in kidneys of
      cattle with contagious bovine pleuropneumonia (CBPP).
AB  - Between 1990 and 1993, 61 outbreaks of contagious bovine pleuropneumonia (CBPP)
      were reported in Lombardy, Northern Italy. In this study, gross pathological
      examination was carried out on 3129 slaughtered cattle, 716 of which (22.9%)
      showed typical CBPP pulmonary lesions. Single or multiple renal infarcts at
      different stages of development were observed in 88 (12.2%) of these 716 cattle.
      The kidneys of 77 cattle whose lungs showed typical CBPP lesions and were
      bacteriologically and immunohistochemically positive for the small colony type of
      Mycoplasma mycoides subspecies mycoides (M. m. mycoides SC) were selected and
      submitted to histological, immunohistochemical and bacteriological examination.
      Histologically, in chronic CBPP cases, infarcts were characterized by fibrosis,
      calcification of cortical tubules and tubular atrophy, accompanied by the
      presence of interstitial inflammatory infiltrates composed of lymphocytes, plasma
      cells and histiocytes. M. m. mycoides SC antigen was detected
      immunohistochemically in 65 (84.4%) of the 77 kidneys examined. The antigen was
      detected in the lumen of blood vessels and in glomerular cells. Immunolabelled
      interstitial cells and tubular epithelial cells were seen in chronic cases only.
      M. m. mycoides SC was isolated from the kidneys of 12 animals (15.6%) and more
      frequently in cases with renal infarcts. This study confirms previous
      observations that demonstrated a renal involvement in cases of CBPP. Moreover,
      the immunohistochemical results indicated that M. m. mycoides SC antigen was
      frequently detectable in different renal structures and cells in spontaneous
      cases of CBPP.

PMID- 11222006
TI  - Post-mortem findings in harbour porpoises (Phocoena phocoena) from the German
      North and Baltic Seas.
AB  - Between 1991 and 1996, necropsies were performed on 445 harbour porpoises
      (Phocoena phocoena), in various states of preservation, stranded on German coasts
      or accidentally caught by German fishermen. The animals originated from the North
      and Baltic Seas, and 133 were considered suitable for histopathological,
      immunohistochemical and microbiological examination. Most of the lesions in these
      133 porpoises were caused by parasites, in particular in the respiratory tract,
      two-thirds of the animals exhibiting pneumonia associated with the parasites.
      Pneumonia was considered to be the cause of death in 46% of the stranded subadult
      and adult animals. The findings gave no evidence of any epidemic due to bacterial
      or viral infection. Bacteriological examination suggested that pneumonia was
      mainly caused by secondary bacterial infection and not by parasitic infestation
      alone. Beta-haemolytic streptococci were considered to be the main infectious
      agents. Morbillivirus antigen was not detected immunohistochemically.

PMID- 11222007
TI  - Bax/bcl-2: cellular modulator of apoptosis in feline skin and basal cell tumours.
AB  - Bcl-2 and bax are two members of the BCL-2 gene family that play a prominent role
      in the regulation of apoptosis. Bax and bcl-2 expression were examined
      immunohistochemically in normal (healthy) feline skin and in 24 benign feline
      cutaneous basal cell tumours. The tumours were also examined for cellular
      proliferation by measurement of reactivity for the proliferation marker Ki-67,
      and for apoptosis by in-situ labelling for fragmented DNA. Bcl-2 was detected in
      normal basal epithelium and in 23 of 24 basal cell tumours. Bax was detected in
      both basal and suprabasal epithelium, but in only seven of 24 tumours. For
      tumours that expressed both bax and bcl-2, the bax:bcl-2 ratio was low. Neither
      bax nor bcl-2 expression was detected in 14 feline cutaneous squamous cell
      carcinomas. Basal cell tumours showed modest cellular proliferation (median,
      17.5% Ki-67- reactive cells), but few (less than 1%) apoptotic cells. The slow,
      indolent growth of feline cutaneous basal cells in these benign skin tumours may
      be a response, at least in part, to opposing regulatory expressions of bcl-2 and
      bax.

PMID- 11222008
TI  - Immunohistochemical analysis of equine pulmonary granular cell tumours.
AB  - Histopathological and immunohistochemical examinations were made on four female
      horses aged 9-12 years with pulmonary granular cell tumours (GCTs). The tumours,
      which were multiple, of varying size, firm and off-white in colour, surrounded
      the bronchi and bronchioles. Metastatic lesions were not detected. The tumour
      cells had abundant eosinophilic cytoplasm filled with prominent coarse
      eosinophilic granules. Immunohistochemically, these tumour cells reacted
      uniformly with vimentin and S100 antibodies. Most were immunolabelled by
      antibodies against glial fibrillary acidic protein (GFAP), myelin basic protein
      (MBP) and protein gene product 9.5 (PGP9.5), and a few cells were positive with
      Leu7 antibody. However, the tumour cells did not react with antibodies against
      neurofilament protein (NF), cytokeratin (CK), chromogranin, alpha1
      antichymotrypsin (AACT), myoglobin, desmin, alpha-actin or alpha-smooth muscle
      actin (alpha-SMA). These immunohistochemical properties of tumour cells support
      the hypothesis that equine pulmonary GCTs are derived from Schwann cells of the
      peripheral nervous system in peribronchial and peribronchiolar tissues. GFAP,
      MBP, Leu7 and PGP9.5 antibodies should help to distinguish equine granular cell
      tumours from other tumours.

PMID- 11222009
TI  - Spontaneous tumours in captive African hedgehogs (Atelerix albiventris): a
      retrospective study.
AB  - Forty tumours were diagnosed in 35 (53%) of 66 captive African hedgehogs
      documented at Northwest ZooPath (NZP) between 1994 and 1999. Three hedgehogs had
      more than one type of tumour and the remaining 32 had a single type. Of the 35
      hedgehogs with tumours, 14 were female, 11 were male, and 10 were of unknown
      gender; 21 were from zoological parks and 14 were privately owned. Twenty of the
      hedgehogs with tumours were adult (>1 year old) with a median age of 3.5 years
      (range 2-5.5 years); 15, of unreported age, were classified as adult. Thirty-four
      (85%) of the 40 tumours were classified as malignant and six (15%) as benign. The
      integumentary, haemolymphatic, digestive and endocrine systems were common sites
      for tumours. The most common tumours were mammary gland adenocarcinoma, lympho
      sarcoma and oral squamous cell carcinoma.

PMID- 11222010
TI  - Distribution of rabbit haemorrhagic disease virus RNA in experimentally infected
      rabbits.
AB  - Adult rabbits were inoculated with liver homogenate from a rabbit that died in a
      Japanese outbreak of rabbit haemorrhagic disease (RHD). All experimentally
      infected rabbits died with typical clinical, gross and histological findings of
      RHD. Distribution of RHD virus in tissues of the infected rabbits was studied by
      non-isotopic in-situ hybridization. Both viral plus- and minus-strand RNAs were
      detected within the cytoplasm of hepatocytes, Kupffer cells and splenic and
      alveolar macrophages, mainly in morphologically intact cells. Strand-specific
      reverse transcriptase-polymerase chain reaction also demonstrated viral minus
      strand RNA as well as plus-strand RNA in the liver, lung and spleen of infected
      rabbits. These results suggest that viral replication occurs not only in
      hepatocytes but also in macrophages. The infected macrophages may contribute to
      viral dissemination in RHD.

PMID- 11222011
TI  - Neuronal and fibre organization in neocortical grafts placed in post-ischaemic
      adult rat brain: a three-dimensional confocal microscopy study.
AB  - The dendritic morphology in neocortical grafts was studied with three-dimensional
      confocal laser scanning microscopy after microinjection of Lucifer Yellow into
      individual cells. The grafts had been implanted into infarct cavities in the
      neocortex of hypertensive rats 46 weeks earlier. The carbocyanine dye method was
      used to identify afferent (host to transplant) and efferent (transplant to host)
      connections. Pyramidal, nonpyramidal and glial cells were present in the
      transplants. Some dendrites had an almost normal appearance, but abnormalities
      (atypical orientation of apical, basal or oblique apical dendrites) were
      observed. Some bi-apical pyramidal neurons and pyramidal neurons with obliquely
      oriented apical dendrites were also observed. Carbocyanine dye-labelled fibres of
      different diameter formed a dense network in the transplant, enabling the border
      between transplant and host tissue to be clearly recognized. No labelled fibres
      were observed to enter the host brain. Fibres with "boutons en passant" and no
      preferential orientation were noted. It is proposed that Lucifer Yellow
      microinjection may be a useful method in studies aimed at improving graft
      morphology. Failure to demonstrate host to transplant connections with the
      carbocyanine dye method was contrary to earlier studies in which tracers were
      applied in vivo. A combined use of in-vivo and post-mortem tracer techniques is
      needed to establish the reason for the discrepancy.

PMID- 11222012
TI  - Bone marrow response to acute and chronic Trypanosoma congolense infection in
      multimammate rats (Mastomys coucha).
AB  - The femoral bone marrow of multimammate rats (n=90), aged 3-8 weeks,
      experimentally infected with different doses of Trypanosoma congolense was
      examined by light and electron microscopy. Some animals died from trypanosomosis,
      but groups of 10 were killed at 4-8, 9-16, 20-24, 30, 40, 50 and 60 days post
      infection (dpi). In the acute stage of infection (4-8 dpi) the bone marrow
      invariably showed a striking increase in erythropoiesis, characterized by an
      increase in the number of mitotic figures and erythroblastic islands and by a
      marked decrease in the myeloid:erythroid cell ratio. Later in the infection,
      erythropoietic activity decreased, while erythrophagocytosis, granulopoiesis,
      megakaryopoiesis and plasma cell population increased. In chronic infection (16
      60 dpi), erythropoietic activity decreased, while intra- and extra-vascular
      erythrophagocytosis greatly increased. There was also an increase in the bone
      marrow stroma cells. Excessive erythrophagocytosis by these cells led to the
      formation of myelin figures and cytoplasmic telephagolysosomes. Degeneration and
      necrosis of neutrophils lining the adluminal surfaces of the blood sinuses were
      observed. It is concluded that in the acute stage of the infection, the bone
      marrow is responsive to the anaemia and that in the chronic stage,
      dyserythropoiesis and increased erythrophagocytosis by the expanded and activated
      cells of the mononuclear phagocytic system play an important role in the
      production of anaemia.

PMID- 11222013
TI  - Effect of impact on different regions of the head of lambs.
AB  - The heads of anaesthetized lambs aged 4-5 weeks were subjected to impact
      (temporal, frontal or occipital) of constant strength with a humane stunner. Two
      hours later, the brains were perfusion-fixed with 4% paraformaldehyde and serial
      whole coronal slices processed by routine methods. Sections were stained with
      haematoxylin and eosin or labelled with a monoclonal antibody to amyloid
      precursor protein, a sensitive marker of axonal injury and neuronal reaction.
      Microscopical evaluation of axonal, neuronal and vascular damage was performed
      with a quantitative grid system. Frontal impact produced the greatest damage,
      followed by occipital then temporal impact. An unusual lesion found in the
      majority of lambs subjected to impact was multifocal necrosis of the cerebellar
      granular layer. The findings should assist clinicians in evaluating the probable
      outcome of traumatic head injury in domestic animals.

PMID- 11222014
TI  - Ehrlichial proliferation and acute hepatocellular necrosis in immunocompetent
      mice experimentally infected with the HF strain of Ehrlichia, closely related to
      Ehrlichia chaffeensis.
AB  - Ehrlichia chaffeensis, the agent of human monocytic ehrlichiosis, is closely
      related to the HF strain of Ehrlichia isolated from ticks in Japan. In this
      study, BALB/c mice inoculated intraperitoneally with the HF strain developed
      severe illness and died at about day 9 post-inoculation. At necropsy, diffuse
      liver necrosis was evident. Ehrlichial microcolonies were observed in endothelial
      cells, monocytes and macrophages of the liver, bone marrow, spleen, thymus, and
      large and small intestine. Immunocompetent mice infected with the HF strain would
      provide a useful model for studying pathogenesis and immunity in acute and severe
      ehrlichiosis caused by E. chaffeensis and related Ehrlichia spp.

PMID- 11222015
TI  - The distribution of leucocyte subsets in the small intestine of healthy cats.
AB  - The aim of this study was to investigate the distribution of leucocyte subsets in
      the small intestine of healthy adult cats (n=16). Immunohistochemical methods
      were used to identify leucocyte subsets within the mucosa of the duodenum,
      jejunum and ileum. Computer-aided morphometry was used to enumerate cells within
      the epithelial compartment, villous lamina propria and lamina propria adjacent to
      upper and lower crypt. Throughout the small intestine, IgA+ and IgM+ plasma cells
      were more prominent in the lamina propria adjacent to the lower crypt than in the
      villus, whereas IgG+ plasma cells were present in equal numbers in the crypt and
      villous regions. Overall, IgA+ plasma cells predominated and IgM+ plasma cells
      were higher in number than IgG+ plasma cells at each of the three anatomical
      locations. By contrast, T cells (CD3+) and T-cell subsets (CD4+ and CD8+) were
      present in greater numbers in the villous lamina propria than in the lamina
      adjacent to the crypts. Intraepithelial lymphocytes (IELs) were also
      characterized phenotypically, the majority being CD8+ T lymphocytes. Lamina
      propria macrophages and dendritic cells were characterized by expression of L1
      and major histocompatibility complex (MHC) class II, and MHC class II expression
      by enterocytes overlying Peyer's patches, although rare, was also shown. The
      qualitative and quantitative data from this study provide a basis for comparison
      with cats with inflammatory enteropathies.

PMID- 11222016
TI  - Macrophage-like cell line (HS-P) from a rat histiocytic sarcoma.
AB  - With future exploration of macrophage properties in mind, we established a novel
      cell line (HS-P) from a transplantable histiocytic sarcoma, derived originally
      from a tumour in an aged F344 rat. HS-P was subjected to 70 serial passages, in
      which the mean doubling time was 15.7 h. The cells, which were round, oval or
      polygonal in shape, were arranged in a compact sheet. They reacted to varying
      degrees for lysosomal enzymes (acid phosphatase and non-specific esterase) and
      with the following antibodies: ED1/ED2 (rat macrophage/histiocyte-specific), OX6
      (rat MHC class II-specific), lysozyme antibody and alpha1-antichymotrypsin
      antibody. Electron microscopically, HS-P cells showed lysosomes and prominent
      cell projections. These findings indicated that the cultured cells were
      macrophage-like. Syngeneic rats inoculated subcutaneously or intraperitoneally
      with HS-P cells invariably developed sarcomatous tumours consisting of
      monomorphic mononuclear cells, which exhibited cytochemical properties similar to
      those of cultured HS-P cells. Bioassay and reverse transcription-polymerase chain
      reaction methods revealed that tumour necrosis factor-alpha increased on addition
      of lipopolysaccharide (LPS), indicating that HS-P cells remained LPS-responsive.
      HS-P cells may prove to be a useful tool for in-vitro studies of macrophage
      function.

PMID- 11222017
TI  - Comparative aspects of plasma antioxidant status in sheep and goats, and the
      influence of experimental abomasal nematode infection.
AB  - This paper provides, for the first time, comparative data on the plasma
      antioxidant status of two ruminant species, namely sheep and goats. In addition,
      the influence of experimental infection with Teladorsagia circumcincta on
      antioxidant status in the same two species is compared and contrasted. In general
      terms, antioxidant status was significantly higher in uninfected kids than in
      lambs. Differences in protein sulphydryl groups and vitamin E concentrations were
      particularly noteworthy; trends were similar, however, for albumin, vitamin A and
      total antioxidant capacity (TAC). Parasitological results, based on worm burden,
      faecal egg counts and peripheral blood eosinophil numbers, confirmed that goat
      kids were more susceptible than lambs to experimental T. circumcincta infection.
      "Trickle infection" had a variable impact on both total and individual
      antioxidant status; particularly during the early weeks, the trend was for
      reduced values in lambs and increased values in kids, as compared with uninfected
      controls. Subsequent challenge infection was associated with a transient decrease
      in TAC and albumin in trickle-infected animals of both species, and in
      appropriate control animals. The observed differences in plasma antioxidant
      capacity between sheep and goats may have important implications in terms of the
      comparative resilience of sheep and goats to parasite infection.

PMID- 11222018
TI  - Immunohistochemical characterization of hepatic lesions associated with migrating
      larvae of Ascaris suum in pigs.
AB  - This paper describes the histopathological features and the cellular distribution
      of T lymphocytes (CD3), B cells (CD79a), immunoglobulin (IgG, IgA, IgM)-bearing
      plasma cells, macrophages (Mac387 and alpha-1-antitrypsin), MHC class II antigen
      and S-100 protein in hepatic white spots associated with naturally occurring
      Ascaris suum parasitism in 35 pigs. Hepatic granulomas were observed in 10 pigs,
      whereas lymphoid proliferation with a diffuse or lymphonodular pattern was the
      main histopathological lesion in 14 other pigs, and portal fibrosis in a further
      11 animals. In lymphonodular lesions, the distribution of immunoreactive cells
      with all antibodies tested was closely similar to that found in the cortex of
      lymph nodes. Thus, lymphoid follicles were composed mainly of CD79a(+)B cells and
      interfollicular tissue was composed mainly of CD3(+)T lymphocytes. The presence
      of follicular dendritic and interdigitating cells expressing S-100 protein and
      MHC class II antigen in lymphonodular lesions suggested that these are highly
      organized structures developed to enhance antigen presentation to B and T cells,
      and consequently the local immune response against the parasite. The humoral
      local response was represented mainly by IgG-secreting plasma cells.

PMID- 11222019
TI  - Canine distemper in a genet (Gennetta gennetta), associated with endogenous lipid
      pneumonia.
AB  - This report describes the histological and immunohistochemical findings in an
      adult male genet (Gennetta gennetta) which died a few hours after being found
      lying in a forest in Lugo (north-western Spain). Subpleural, yellowish, firm foci
      were found in the lung. Histopathological examination confirmed a diagnosis of
      endogenous lipid pneumonia. Microscopical lesions that gave rise to a suspicion
      of canine distemper virus (CDV) infection included lymphoid depletion, non
      suppurative encephalitis and demyelination in the central nervous system, and the
      presence of inclusion bodies in renal tubules. Immunohistochemical examination
      was performed with the streptavidin-biotin-complex method and a monoclonal
      antibody against the nucleocapsid protein (NP) of CDV. Antigen was detected in
      epithelial, nervous and lymphoid cells in several organs. This would appear to be
      the first report of distemper-like infection in a genet.

PMID- 11222020
TI  - Immunohistochemical detection of galectin-3 in canine gastric carcinomas.
AB  - Galectin-3 was detected immunohistochemically in nine canine gastric carcinomas.
      In normal gastric tissue adjacent to the neoplasms, the gastric epithelial cells
      showed faint immunolabelling for galectin-3, but in all the tumours the
      neoplastic cells showed moderate to strong immunolabelling. Galectin-3 was
      localized in the cytoplasm of the normal mucosal cells, whereas it was found in
      both the cytoplasm and the nucleus of the neoplastic cells. Positive cells
      typically exhibited dark brown coloration of the nucleus or cytoplasm, without
      background labelling. The results suggest that galactin-3 has a
      pathophysiological role in canine gastric carcinoma.

PMID- 11222021
TI  - Orchitis in a cat associated with coronavirus infection.
AB  - A case of severe, pyogranulomatous and necrotizing orchitis in a cat, which later
      succumbed to systemic feline infectious peritonitis (FIP), is described. The 3.5
      year-old cat, positive for feline immunodeficiency virus infection, presented
      with a left testicular enlargement. A few months after castration the animal was
      humanely destroyed due to declining health. Post-mortem examination revealed
      inflammatory lesions in abdominal organs and in the brain compatible with FIP.
      Infection was confirmed with a reverse transcriptase-polymerase chain reaction
      test and by immunohistochemical demonstration of coronavirus antigen in the
      affected tissues, including the left testicle. FIP is usually a systemic disease.
      However, lesions and presenting clinical signs in a single organ system such as
      the brain are not uncommon. The results of this case study indicate that
      orchitis, although rare, should be on the list of lesions of FIP.

PMID- 11222022
TI  - A joint myxoma in a dog.
AB  - Myxomas of the joints are extremely rare in domestic animals, only four cases,
      all in dogs, having been reported previously. This paper describes a myxoma
      originating from the synovium of the right radiocarpal joint of a mature female
      Dobermann pinscher with right front limb lameness. The tumour was excised
      surgically and no recurrence was detected during a 2-year follow-up period.
      Immunohistochemically, the tumour cells reacted with antibodies to vimentin and
      S100 protein but not with antibodies to cytokeratins (high and low molecular
      weight) or human callus keratin.

PMID- 11222023
TI  - Papillary meningioma in the dog: a clinicopathological study of two cases.
AB  - Two cases of canine papillary meningioma are reported. The first animal, an 11
      year-old male Boxer, presented with vestibular ataxia and the tumour was located
      in the left pontomedullary region. The second animal, a 15-year-old female cross
      bred Miniature Poodle, presented with dementia, truncal ataxia and hypermetria,
      and the tumour was located in the right semilunar ganglion of Gasser. In the
      first case, histopathological examination showed that the papillary pattern
      merged with a typical syncytial meningioma, with extensive areas of necrosis. In
      the second case, the multilobular tumour had lobules with a purely syncytial,
      fibrous or transitional histological pattern, and lobules with intermingling
      papillary and secretory histological patterns. Both tumours exhibited
      histological features of malignancy, but evidence of remote metastasis was not
      found.

PMID- 11222024
TI  - Ice nucleation and antinucleation in nature.
AB  - Plants and ectothermic animals use a variety of substances and mechanisms to
      survive exposure to subfreezing temperatures. Proteinaceous ice nucleators
      trigger freezing at high subzero temperatures, either to provide cold protection
      from released heat of fusion or to establish a protective extracellular freezing
      in freeze-tolerant species. Freeze-avoiding species increase their supercooling
      potential by removing ice nucleators and accumulating polyols. Terrestrial
      invertebrates and polar marine fish stabilize their supercooled state by means of
      noncolligatively acting antifreeze proteins. Some organisms also depress their
      body fluid melting point to ambient temperature by evaporation and/or solute
      accumulation.

PMID- 11222025
TI  - Noninvasive monitoring of citrate, acetate, lactate, and renal medullary osmolyte
      excretion in urine as biomarkers of exposure to ischemic reperfusion injury.
AB  - Injury during the transplant process affects the alloantigen-dependent factors
      and the alloantigen-independent processes of "chronic" rejection. Consequently,
      the determination of reliable parameters for the assessment of ischemic damage is
      essential for the prediction of renal changes after ischemia/reperfusion injury.
      The aim of this study was to assess the ability of (1)H NMR spectroscopy to
      predict the early graft dysfunction in an ischemia/reperfusion model after
      preservation in two standard preservation solutions, Euro-Collins (EC) and
      University of Wisconsin (UW). The second aim was to specify the role of the UW
      solution in preventing renal medullary injury. Urine and plasma samples from
      three experimental groups were examined during 2 weeks: control group (n = 5), EC
      group (cold flushed and 48-h cold storage of kidney in EC and
      autotransplantation, n = 12), and UW group (cold flushed and 48-h cold storage of
      kidney in UW and autotransplantation; n = 12). We also examined these kidneys 30
      40 min after implantation and on the sacrifice day. Creatinine clearance was
      significantly reduced in the EC group during the second week. Fractional
      excretion of sodium and urine N-acetyl-beta-d-glucosaminidase activity were
      improved but not significantly different in the preserved groups. Urinary
      concentrations of the alpha-class glutathione S-transferase were significantly
      greater in the EC group during the first week after transplantation. The most
      relevant resonances for evaluating renal function after transplantation
      determined by (1)H NMR spectroscopy were those arising from citrate,
      dimethylamine (DMA), lactate, and acetate in urine and trimethylamine-N-oxide
      (TMAO) in urine and plasma. These findings suggest that graft dysfunction is
      associated with damage to the renal medulla determined by TMAO release in urine
      and plasma associated with DMA and acetate excretion. Citrate is also a urinary
      marker that can discriminate kidneys with a favorable evolution. Our results
      suggest that (1)H NMR spectroscopy is an efficient technique for detecting
      ischemic damage when accurate and precise data on graft injury is required. In
      addition, this study outlines the specific impact of the UW solution against
      injury to the renal medulla.

PMID- 11222026
TI  - Hypothermic storage of coronary endothelial cells reduces nitric oxide synthase
      activity and expression.
AB  - Preservation with University of Wisconsin (UW) solution has been implicated in
      coronary artery endothelial damage and loss of endothelium-dependent
      vasodilatation. Therefore, the objective of this study was to investigate the
      effect of this solution on basal nitric oxide (NO) release from porcine coronary
      endothelial cells (CEC). Cultures were exposed to cold (4 degrees C) storage in
      UW solution for 6, 8 and 12 h. Parallel cultures were incubated with control
      medium at 37 degrees C. After treatment, NO release was evaluated by nitrite
      production, a stable metabolite of NO. Activity of the constitutive endothelial
      nitric oxide synthase (eNOS) was measured by the conversion [3H]-l-arginine to
      [3H]-l-citrulline and eNOS protein expression by Western blotting. Nitrite
      production by control cells was augmented with increasing times of incubation,
      whereas no change was observed in those cultures preserved with UW solution.
      Activity of eNOS was significantly decreased compared to the respective control
      group by cold storage of cells for longer periods than 6 h. Such decrease was
      correlated with a diminished eNOS protein expression in CEC preserved with UW
      solution after 8- and 12-h storage. These results suggest that prolonged
      hypothermic storage of CEC with UW solution does not preserve basal NO release
      because of a certain loss of eNOS protein, which may contribute to the reported
      injury of heart transplants after long-term preservation.

PMID- 11222027
TI  - Marked difference in tumor necrosis factor-alpha expression in warm ischemia- and
      cold ischemia-reperfusion of the rat liver.
AB  - Although tumor necrosis factor-alpha has been implicated in liver injury after
      both warm ischemia- and cold ischemia-reperfusion, it is unclear whether
      reactivity of the liver to these stimuli is similar with regard to cytokine
      expression. Here we compare the effects of warm and cold ischemia on tumor
      necrosis factor-alpha expression and test the hypothesis that cold ischemia
      preceding warm ischemia causes overexpression of this cytokine. Rat livers were
      flushed out with University of Wisconsin solution and subjected to varying
      periods of warm ischemia, cold ischemia, or cold ischemia plus warm ischemia
      followed by reperfusion using a blood-free perfusion model. Tumor necrosis factor
      alpha and interleukin-10 release into the perfusate and bile were measured by
      ELISA, and expression of these cytokines and that of c-fos, c-jun, and c-myc were
      studied by reverse-transcriptase polymerase chain reaction. We found high levels
      of tumor necrosis factor-alpha in the perfusates of livers subjected to warm
      ischemia-reperfusion, whereas minimal or no tumor necrosis factor-alpha was
      detected in livers subjected to cold ischemia-reperfusion or to cold ischemia
      plus warm ischemia-reperfusion. Reverse-transcriptase polymerase chain reaction
      confirmed the above findings and showed that immediate early genes were expressed
      in reperfused groups of livers. Measurements of cytokine release into bile showed
      that neither tumor necrosis factor-alpha nor interleukin-10 were upregulated by
      cold ischemia-reperfusion. The results suggest that (1) warm ischemia- and cold
      ischemia-reperfusion of rat liver lead to very different outcomes with regard to
      tumor necrosis factor-alpha expression and (2) cold ischemia preceding warm
      ischemia prevents upregulation of tumor necrosis factor-alpha.

PMID- 11222028
TI  - A comparison of a sucrose-based solution with other preservation media for cold
      storage of isolated hepatocytes.
AB  - A sucrose-based solution has been compared with other preservation solutions
      (University of Wisconsin (UW) solution and Marshall's citrate solution, with
      Dulbecco's medium as control) during hypothermic preservation of isolated rat
      hepatocytes for up to 72 h. Studies on the stability of liver cells at low
      temperature by exclusion of trypan blue dye and morphological appearance were
      conducted. During storage beyond 24 h, there was a clear difference between cells
      stored in Dulbecco's medium and Marshall's citrate and those stored in sucrose
      based solution and UW solution, with the former storage groups showing many cells
      developing large membrane "blebs" and the latter storage groups maintaining a
      more typical morphology and developing only small membrane protrusions. Dye
      exclusion was higher in sucrose-based solution (48 h, 75 +/- 7%; 72 h, 65 +/- 6%)
      and UW solution (48 h, 72 +/- 5%; 72 h, 63 +/- 4%) than in Marshall's citrate (48
      h, 31 +/- 5%; 72 h, 10 +/- 1%) and Dulbecco's medium (48 h, 8 +/- 2%; 72 h, 5 +/-
      1%). These data suggest that sucrose-based solution should be investigated
      further as a less complex alternative solution for storage of isolated
      hepatocytes.

PMID- 11222029
TI  - The lower hydrolysis of ATP by the stress protein GroEL is a major factor
      responsible for the diminished chaperonin activity at low temperature.
AB  - The chaperonins GroEL and GroES were shown to facilitate the refolding of urea
      unfolded rhodanese in an ATP-dependent process at 25 or 37 degrees C. A
      diminished chaperonin activity was observed at 10 degrees C, however. At low
      temperature, GroEL retains its ability to form a complex with urea-unfolded
      rhodanese or with GroES. GroEL is also able to bind ATP at 10 degrees C.
      Interestingly, the ATPase activity of GroEL was highly decreased at low
      temperatures. Hydrolysis of ATP by GroEL was 60% less at 10 degrees C than at 25
      degrees C. We conclude that the reduced hydrolysis of ATP by GroEL is a major but
      perhaps not the only factor responsible for the diminished chaperonin activity at
      10 degrees C. GroEL may function primarily at higher temperatures in which the
      ability of GroEL to hydrolyze ATP is not compromised.

PMID- 11222031
TI  - The use of biomarkers in Daphnia magna toxicity testing V. In vivo alterations in
      the carbohydrate metabolism of Daphnia magna exposed to sublethal concentrations
      of mercury and lindane.
AB  - Aspects of the carbohydrate metabolism of Daphnia magna exposed for 48 and 96 h
      to sublethal concentrations of mercury and lindane were investigated. General as
      well as toxicant-specific perturbations in the intermediary metabolism were
      observed. Both model toxicants caused an increase in glycolytic and hexose
      monophosphate shunt activity. Mercury exposure increased lactate dehydrogenase
      and isocitrate activity (only after 96 h), while lindane exposure, on the
      contrary, inhibited the cellular lactate formation and increased the Krebs' cycle
      activity (only after 48 h). Daphnids exposed to sublethal mercury concentrations
      clearly exhibited increased glycogenolytic activity, while in lindane-exposed
      organisms mainly glycogen phosphorylase inhibition was detected. The short-term
      enzyme-based effect levels (48--96 h LOEC and EC(10) values) were compared with
      the effects on the population dynamics. This evaluation for both model toxicants
      suggests that threshold levels (LOEC or EC(10) values) based on pyruvate kinase
      activity after 48 and 96 h of exposure could be potential early warning signals
      for long-term effects. A set of enzymatic endpoints, based on the intermediary
      metabolism, is suggested to characterize the metabolic state of the daphnids.

PMID- 11222032
TI  - Complex dynamics of adaptation in a nonaxenic microcystis culture. 1. Effects of
      dinitrophenol on population growth.
AB  - Chronic exposure to toxicants is a selective pressure affecting populations and
      also the interactions between populations. Nonaxenic cultures of the blue-green
      alga Microcystis aeruginosa were used to investigate the ecological dynamics and
      the effect of preexposure to 2,4-dinitrophenol (DNP) on the tolerance toward
      subsequent DNP inputs. It was predicted that preexposure would induce an
      increased tolerance to further inputs. This should cause a higher population
      growth rate under a given DNP exposure, a broader tolerance range (the range of
      concentrations over which population growth can be sustained), a higher EC(50),
      and a lesser variability in growth rates, over the range of experimental exposure
      concentrations. DNP reduced Microcystis growth proportionally to exposure
      concentration. Light, inorganic carbon, and DNP were likely limiting factors for
      algal growth. Heterotrophic bacteria presumably used the dead cells and the
      exudate of living algae as substrates. Some unexpected effects occurred, such as
      an apparent increase in dissolved DNP in the medium following its initial decline
      and fluctuations of the bacterial population. The hypotheses were verified as
      concerns the effect of preexposure on tolerance. Changes were apparent in the
      EC(50) and in the breadth of the tolerance range. Moreover, the variability of
      preexposed populations, in terms of algal growth rate, over the range of exposure
      concentrations, was smaller than that of non-preexposed populations. Such a
      decrease in variability may reduce the potential of a population to resist
      further stresses.

PMID- 11222033
TI  - Complex dynamics of adaptation in a nonaxenic microcystis culture. 2. Computer
      simulation of dinotrophenol effects.
AB  - A hypothesis was modeled to account for complex 20-day dynamics in a culture of
      blue-green algae Microcystis and heterotrophic bacteria exposed to 2,4
      dinitrophenol (DNP). In trials with little or no added DNP, a limiting factor
      (light or CO(2)) may cause algal density to fluctuate after 14 days of increase.
      Such factors may be unimportant at levels of DNP that restrict photosynthesis.
      Bacterial growth may be limited by organic substrate, and bacteria may be more
      resistant to DNP than blue-green algae. Hence, at intermediate levels of DNP,
      substrate provided by increased algal death stimulates bacterial growth more than
      DNP retards it, causing a bacterial peak. Sorption of DNP to cells may cause the
      DNP decline. Greater growth and slower DNP decline in experiments with preexposed
      organisms indicate lower DNP sorption affinity in preexposed cells. Bacterial
      assimilation of DNP-containing substrate may cause the reappearance of DNP. The
      model reproduced the fluctuation in algal density after growth was limited and
      better growth and lower DNP decline with preexposed organisms. Reappearance of
      DNP occurred, but was not obvious. Bacterial dynamics were least well reproduced.
      Changes in bacterial constants most affected output. Despite model inadequacies,
      probable aspects of toxicant action in nature have been revealed. Ecological
      relationships among populations of different species and genetic differences
      among individuals may have led to lower than expected toxicity, adaptation, and
      even growth stimulation. Responses of single species tested in isolation may be
      inadequate to predict toxicant impact.

PMID- 11222034
TI  - Stress responses and changes in protein metabolism in carp Cyprinus carpio during
      cadmium exposure.
AB  - Stress responses and changes in protein metabolism were studied in common carp
      Cyprinus carpio exposed to 0, 0.8, 4, and 20 microM cadmium (Cd) over a 29-day
      period. Blood and other tissue samples were taken after 4 and 29 days of
      exposure. The highest Cd concentration proved to be lethal to the fish, resulting
      in 100% mortality after 21 days of exposure. Cd accumulated in the tissues in the
      following order: kidney>liver>gills. Blood hematocrit, blood hemoglobin, plasma
      glucose, plasma lactate, and tissue total protein contents were not significantly
      altered. The concentrations of Cd and zinc (Zn) binding metallothioneins ((Cd,
      Zn)-MTs) were in the following order=liver>kidney>gills. An increase in (Cd, Zn)
      MTs was observed at all exposure concentrations at days 4 and 29 in kidney and at
      Day 29 in gills. No significant changes in (Cd, Zn)-MT contents were found in
      liver. The concentrations of free amino acids and the activities of proteases
      were increased at Day 4 in gills, liver, and kidney of carp exposed to 4 and 20
      microM Cd, and in gills and kidney at Day 29 in carp exposed to 4 microM Cd. The
      observed increases in the activities of aspartate aminotransferase and alanine
      aminotransferase suggest that the observed proteolysis is intended to increase
      the role of proteins in the energy production during Cd stress. However, this
      increased activity of both aminotransferases was not found in gills during
      exposure to the lethal Cd concentration, indicating that Cd may also cause an
      inhibitory effect on the activity of these enzymes above a certain level.

PMID- 11222035
TI  - In vivo effects of inorganic mercury (HgCl(2)) on striatal dopaminergic system.
AB  - In the present study, the effects of intrastriatal administration of different
      concentrations (40 microM, 400 microM, and 4 mM) of inorganic mercury (HgCl(2))
      on the dopaminergic system of rat striatum were evaluated, using a microdialysis
      technique coupled to liquid chromatography-electrochemical detection. In previous
      studies, we discussed the effects of organic mercury (MeHg) administration on the
      striatal dopaminergic system on the basis of changes in the release and
      metabolism of striatal dopamine (DA). In the present study it is demonstrated
      that intrastriatal administration of all concentrations of HgCl(2) produced
      significant increases in the output of DA (1240, 2500, and 2658% for the
      concentrations of 40 microM, 400 microM, and 4 mM HgCl(2), respectively) from rat
      striatal tissue, associated with significant decreases in striatal levels of its
      metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) with
      the concentrations of 400 microM and 4 mM HgCl(2) (74.4 and 3.4% for DOPAC and
      71.0 and 50.6% for HVA, respectively), whereas no changes in metabolite levels
      were observed with the concentration of 40 microM HgCl(2). These effects are
      explained as a result of stimulated DA release and/or changed DA metabolism. The
      effects of intrastriatal administration of HgCl(2) were compared with those of
      MeHg on DA extracellular levels.

PMID- 11222036
TI  - Ultrastructural variations in Lethocerus niloticum (Insecta: Hemiptera) caused by
      pollution in Lake Mariut, Alexandria, Egypt.
AB  - Water bugs, Lethocerus niloticum (Hemiptera: Belostomatidae), were collected from
      polluted and unpolluted areas of Lake Mariut to study ultrastructural alterations
      of different organs as a response to mainly heavy metal water pollution in the
      lake. Malpighian tubules are described by light, scanning, and transmission
      electron microscopy. L. niloticum has four Malpighian tubules floating in the
      hemolymph. Each tubule opens separately into the hindgut, consisting of one type
      of epithelium cells, and is divided into four regions. Structural changes in
      cells of the third distinctive region are examined. The most prominent
      pathological changes are the occurrence of pleomorphic mitochondria, the presence
      of enlarged irregular laminated concretions, an increase in lysosomes, and lysis
      of cytoplasm. Indentations of the nucleus and chromatin clumping are observed.
      These results allowed determination of the impact of pollutants in Malpighian
      tubule cells of L. niloticum, and thus this insect can be used as a biomonitor.

PMID- 11222037
TI  - Continuous monitoring of Folsomia candida (Insecta: Collembola) in a metal
      exposure test.
AB  - Current recommended ecotoxicological tests with the parthenogenetic springtail
      Folsomia candida using standard OECD soil do not allow for continuous monitoring
      during the exposure period. Effects of chemicals cannot be determined until the
      end of the experiment (typically after 4 weeks), since the animals stay below the
      soil surface. In this study, F. candida were maintained on a plaster of
      Paris/graphite substrate for 7 weeks and were supplied with an aqueous suspension
      of yeast contaminated with Cd, Cu, Pb, and Zn as nitrate salts. Growth rate, time
      to first batch of eggs, quantity of food consumed, and the presence of graphite
      in the gut (a sign of avoidance of yeast) were all affected by metal contaminated
      diets. The relative toxicities of Cd:Cu:Pb:Zn in the yeast were
      1.0:1.07:12.0:4.3, respectively (on a weight basis) with Cd being the most toxic.
      Internal body concentrations increased, and the concentration factor (metal
      concentration in F. candida/metal concentration in yeast) decreased with
      increasing metal exposure. In general, metals are much less toxic when added to
      the food of F. candida than when incorporated into soil in standard tests. It is
      suggested that Collembola have a greater tolerance of metals in the diet since
      they avoid contaminated food, and are able to excrete assimilated metals at
      moulting via exfoliation of the midgut epithelium where the elements are retained
      as part of a storage--detoxification system. The methodology described in this
      article allows effects on growth to be observed as early as 7 days after the
      beginning of the experiment.

PMID- 11222038
TI  - Acute toxicity of LAS homologues in marine microalgae: esterase activity and
      inhibition growth as endpoints of toxicity.
AB  - The toxicity of two linear alkylbenzene sulfonate (LAS) homologues (C(10) and
      C(13)) was evaluated in four marine microalgae (Nannochloropsis gaditana,
      Tetraselmis suecica, Rhodomonas salina, and Isocrysis galbana), using growth
      inhibition rate and esterase activity (measured by flow cytometry) as endpoints.
      The inhibitor effect was higher for the C(13) LAS homologue than for C(11), in
      both responses analyzed. When both endpoints were compared, the growth inhibition
      rate was between 2 and 5 times more sensitive than esterase activity. Among
      microalgae species, R. salina exhibited the highest sensitivity.

PMID- 11222039
TI  - Long-term toxic impact of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the
      reproduction, sexual differentiation, and development of different life stages of
      Gobiocypris rarus and Daphnia magna.
AB  - The sexual ratio of Gobiocypris rarus exposed to 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) and 17 beta-estradiol from embryo to sexually mature revealed
      feminization and overdevelopment of connective tissue in male fish gonad in 2--30
      pg/L TCDD concentration range. Daphnia magna was not sensitive to the high dose
      of TCDD (0.1--1000 ng/ml), but the reproduction of D. magna treated with TCDD
      decreased after the 8th day. 7-Ethoxyresorufin-O-deethylase (EROD) activities in
      newly fertilized eggs of G. rarus exposed to TCDD dosage groups (1000--100,000
      pg/L) were significantly induced and increased with TCDD concentrations at the
      early life stage, while no difference was found between low TCDD dosage groups
      (<100 pg/L), but a good relationship between the EROD activity and the TCDD
      concentration was observed during a long-term developmental stage. There was a
      pericardial edema formed in a 2-week yolk-sac at the concentration of 1000 pg/L
      TCDD. But in the exposure group (2 pg/L TCDD for 120 days), the cell nuclei of
      hepatocytes was far from the center and packed toward the cell membrane; the
      cristae of most mitochondria in the cell dropped and collapsed; the rough
      endoplasmic reticulum broke into fragments; and numerous lipid droplets formed in
      the cell.

PMID- 11222040
TI  - Suppression of hippocampal slice excitability by 2-, 3-, and 4-methylpyridine.
AB  - The present study assessed the effects of 2-, 3-, and 4-methylpyridine on rat
      hippocampal slice excitability. Tests of excitatory and inhibitory systems in
      area CA1 of the hippocampal slice were conducted over a period of 3 h
      postexposure. Following exposures of 100 microM 2-, 3-, or 4-methylpyridine,
      evoked population excitatory postsynaptic potential and population spike
      responses recorded in the cell body field of hippocampal area CA1 were slowly
      suppressed over the course of 3 h, whereas no effects on local inhibitory
      processes or latency of evoked responses were detected. No significant
      differences were observed between agents.

PMID- 11222041
TI  - Metabolic responses of fish following exposure to two different oil spill
      remediation techniques.
AB  - To assess the impacts of two oil spill remediation techniques on fish metabolism,
      change in aerobic and anaerobic enzyme activities in juvenile Australian Bass,
      Macquaria novemaculeata, was examined. Changes in cytochrome C oxidase (CCO) and
      lactate dehydrogenase (LDH) activities were investigated following exposure to
      the crude oil water accommodated fraction (WAF) and chemically dispersed crude
      oil WAF. There was a significant stimulation in CCO activity in the gills and
      livers of fish exposed to the WAF of Bass Strait crude oil and chemically
      dispersed crude oil, compared to the control treatment. In addition, LDH activity
      was significantly stimulated in the liver of fish exposed to dispersed crude oil
      WAF, compared to the crude oil WAF. Fish exposed to the dispersed crude oil WAF
      treatment had significantly higher oxygen consumption, as measured by oxygen
      depletion in a sealed chamber, than fish exposed to the crude oil WAF and control
      treatments.

PMID- 11222042
TI  - Biodegradability of metronidazole, olaquindox, and tylosin and formation of
      tylosin degradation products in aerobic soil--manure slurries.
AB  - The use of veterinary drugs (primarily antibiotics) in animal husbandry harbors
      the risk that these compounds end up in the farmland when manure is used as
      fertilizer. The biodegradability of three compounds, olaquindox (OLA),
      metronidazole (MET), and tylosin (TYL), was simulated in soil--manure slurries
      with 50 g of soil per liter. Supplemental batch sorption tests revealed that
      insignificant amounts of OLA and MET were located in the soil phase, whereas only
      0.1 to 10% of the added amounts of TYL remained in the liquid phase. This may
      reduce the bioavailability and thus biodegradation rates of TYL. Unidentified
      metabolites of OLA and TYL and four known TYL metabolites were detected using
      HPLC. However, none of these substances were seen to persist in the
      biodegradation experiments, indicating that OLA and TYL most likely were
      mineralized in the experiments. Neither the use of sandy or clayey soil nor the
      use of 0, 1, or 10% (V/V) of manure added to these soils had a significant effect
      on the degradation rates. Degradation half-lives for the primary degradation were
      3.3--8.1 days for TYL, 5.8--8.8 days for OLA, and 13.1--26.9 days for MET. Based
      on comparisons of results obtained with the benchmark chemical aniline and
      degradation half-lives of this compound in nature, it was assessed that results
      obtained with the current test method slightly overestimate real-world
      biodegradation rates.

PMID- 11222044
TI  - A mathematical model of auxin-mediated radial growth in trees.
AB  - A mathematical model is presented to describe the coupling between the
      concentration of indole-3-acetic acid (IAA) in the cambial region of a tree
      branch and the radial expansion of the branch during active growth. The main
      features of the model are (1) the branch cambium is treated as an approximately
      cylindrical surface of negligible thickness, (2) the rate of radial growth is
      proportional to the mass of IAA per unit area on the cambial surface, and (3) IAA
      is transported basipetally through the cambium at a constant speed. We neglect
      the role of elastic strains in the determination of branch shape, and the effects
      of IAA synthesis and metabolization in the cambium, so the model is not
      quantitatively accurate. However, the model does reproduce several important
      qualitative features of tree growth including the approximate area-preserving
      property of tree branch junctions and the ability of a branch to maintain its
      shape despite perturbations due to injury.

PMID- 11222045
TI  - Revisiting the relationship of the mammalian G1 phase to cell differentiation.

PMID- 11222046
TI  - Uncovering biases in high throughput screens of G-protein coupled receptors.
AB  - The ability of high throughput membrane binding assays to detect ligands for G
      protein coupled receptors was examined using mathematical models. Membrane assay
      models were developed using the extended ternary complex model (Samama et al.,
      1993) as a basis. Ligand binding to whole cells was modeled by adding a G-protein
      activation step. Results show that inverse agonists bind more slowly and with a
      lower affinity to receptors in the membrane binding assay than to receptors in
      whole cells, causing the membrane assay to miss pharmaceutically important
      inverse agonists. Assay modifications to allow detection of inverse agonists are
      discussed. Finally, kinetic binding data are shown to provide information about
      ligand efficacy. This work demonstrates the utility of mathematical modeling in
      detecting biases in drug-screening assay, and also in suggesting techniques to
      correct those biases.

PMID- 11222047
TI  - A model of primitive streak initiation in the chick embryo.
AB  - Initiation of the primitive streak in avian embryos provides a well-studied
      example of a pattern-forming event that displays a striking capacity for
      regulation. The mechanisms underlying the regulative properties are, however,
      poorly understood and are not easily accounted for by traditional models of
      pattern formation, such as reaction-diffusion models. In this paper, we propose a
      new activator-inhibitor model for streak initiation. We show that the model is
      consistent with experimental observations, both in its pattern-forming properties
      and in its ability to form these patterns on the correct time-scales for
      biologically realistic parameter values. A key component of the model is a
      travelling wave of inhibition. We present a mathematical analysis of the speed of
      such waves in both diffusive and juxtacrine relay systems. We use the streak
      initiation model to make testable predictions. By varying parameters of the
      model, two very different types of patterning can be obtained, suggesting that
      our model may be applicable to other processes in addition to streak initiation.

PMID- 11222048
TI  - Model selection in non-nested hidden Markov models for ion channel gating.
AB  - An important task in the application of Markov models to the analysis of ion
      channel data is the determination of the correct gating scheme of the ion channel
      under investigation. Some prior knowledge from other experiments can reduce
      significantly the number of possible models. If these models are standard
      statistical procedures nested like likelihood ratio testing, provide reliable
      selection methods. In the case of non-nested models, information criteria like
      AIC, BIC, etc., are used. However, it is not known if any of these criteria
      provide a reliable selection method and which is the best one in the context of
      ion channel gating. We provide an alternative approach to model selection in the
      case of non-nested models with an equal number of open and closed states. The
      models to choose from are embedded in a properly defined general model.
      Therefore, we circumvent the problems of model selection in the non-nested case
      and can apply model selection procedures for nested models.

PMID- 11222049
TI  - Thermoregulation through skin under variable atmospheric and physiological
      conditions.
AB  - Considering three layers of the skin and subcutaneous region, an attempt has been
      made to obtain the analytical and numerical solutions for temperature
      distribution of the bioheat equation. The problem is studied under variable
      physiological parameters and atmospheric conditions. The role of metabolic heat
      generation, blood mass flow and perspiration in different thicknesses have been
      noted. The numerical solutions for different parametric values are shown
      graphically.

PMID- 11222050
TI  - Partnership.
AB  - Individuals are called partners when it is in their best interest to help each
      other, if by doing so they increase the probability of being together in the
      future when, for similar reasons, they will continue to help each other. Kinsmen
      or individuals who often face (hedonic) situations in which helping is the
      dominating strategy are committed to help each other. Partnership may develop
      among them since the loss of the other means the loss of a guaranteed helper.
      Thus, they may be willing to take additional risks to help each other.
      Partnership may occur among unrelated individuals and with no hedonic situations.
      Partnership creates bonds between partners which may be much stronger than those
      between kinsmen; an individual may take more risks for his partner than he will
      ever take for a kin. Partnership may evolve without the sophistication and memory
      required for reciprocation altruism. Although kin selection, partnership and
      reciprocation are likely to appear fused as the causes for altruism, we argue
      that it may be possible to distinguish between them in some situations. We show
      that as the partners get older partnership may become less important to them. We
      also show that like cooperation, and for analogous reasons, malice may evolve
      among partners so that each will be willing to take additional risks in order to
      eliminate the other.

PMID- 11222051
TI  - Double-stranded RNA as a not-self alarm signal: to evade, most viruses purine
      load their RNAs, but some (HTLV-1, Epstein-Barr) pyrimidine-load.
AB  - For double-stranded RNA (dsRNA) to signal the presence of foreign (non-self)
      nucleic acid, self-RNA-self-RNA interactions should be minimized. Indeed, self
      RNAs appear to have been fine-tuned over evolutionary time by the introduction of
      purines in clusters in the loop regions of stem-loop structures. This adaptation
      should militate against the "kissing" interactions which initiate formation of
      dsRNA. Our analyses of virus base compositions suggest that, to avoid triggering
      the host cell's dsRNA surveillance mechanism, most viruses purine-load their RNAs
      to resemble host RNAs ("stealth" strategy). However, some GC-rich latent viruses
      (HTLV-1, EBV) pyrimidine-load their RNAs. It is suggested that when virus
      production begins, these RNAs suddenly increase in concentration and impair host
      mRNA function by virtue of an excess of complementary "kissing" interactions
      ("surprise" strategy). Remarkably, the only mRNA expressed in the most
      fundamental form of EBV latency (the "EBNA-1 program") is purine-loaded. This
      apparent stealth strategy is reinforced by a simple sequence repeat which prefers
      purine-rich codons. During latent infection the EBNA-1 protein may evade
      recognition by cytotoxic T-cells, not by virtue of containing a simple sequence
      amino acid repeat as has been proposed, but by virtue of the encoding mRNA being
      purine-loaded to prevent interactions with host RNAs of either genic or non-genic
      origin.

PMID- 11222052
TI  - Complementarity of ecological goal functions.
AB  - This paper summarizes, in the framework of network environ analysis, a set of
      analyses of energy-matter flow and storage in steady-state systems. The network
      perspective is used to codify and unify ten ecological orientors or extremal
      principles: maximum power (Lotka), maximum storage (Jorgensen-Mejer), maximum
      empower and emergy (Odum), maximum ascendency (Ulanowicz), maximum dissipation
      (Schneider-Kay), maximum cycling (Morowitz), maximum residence time (Cheslak
      Lamarra), minimum specific dissipation (Onsager, Prigogine), and minimum empower
      to exergy ratio (Bastianoni-Marchettini). We show that, seen in this framework,
      these seemingly disparate extrema are all mutually consistent, suggesting a
      common pattern for ecosystem development. This pattern unfolds in the network
      organization of systems.

PMID- 11222053
TI  - A conflict between two evolutionary levels in trees.
AB  - Due to the lack of germ line segregation in plants, it is possible to consider
      plant evolution (but not the evolution of most animals) as being composed of two
      evolutionary levels: 1. Intra-organism, in which the replicating unit is a part
      of the tree (e.g. a branch), reproduction is asexual, mutations are somatic, and
      selection operates only upon traits relevant to vegetative growth. 2. Inter
      organism, in which the replicating unit is the whole tree, reproduction is
      sexual, and selection operates upon all the traits. In this work, a case of a
      conflict between these two levels is studied. The dynamics of a mutation, which
      is advantageous on the branch level but harmful for the whole tree, are discussed
      for a one-locus two-allele model. Several cases are considered: dominant,
      partially dominant, and haploid. Necessary and sufficient conditions for fixation
      of such a mutation are found. The model predicts that as the longevity of a tree
      species increases, the trees are expected to be more strongly shifted from their
      optimal growth-to-reproduction ratio towards growth, and resource allocation
      between branches and other tree parts is expected to be shifted in favor of the
      branches. Traditional approach, considering the second level only, is justified
      as a limit case for short longevity.

PMID- 11222054
TI  - Lesions of the entorhinal cortex impair acquisition of hippocampal-dependent
      trace conditioning.
AB  - Rabbits with the electrolytic lesions of bilateral entorhinal cortex (EC) were
      trained with the hippocampal-dependent trace conditioning of the nictitating
      membrane response. The multiple-unit activity of the hippocampal CA1 region was
      recorded during conditioning. The conditioned stimulus was a tone (1 kHz, 85 dB,
      200-ms duration), the unconditioned stimulus was a corneal air puff (3 psi, 150
      ms duration), and the interstimulus interval was 750 ms. The EC-lesioned animals
      showed only 30% conditioned response (CR) by the ninth session while the sham
      operated animals showed above 80% CR. The lesioned animals did not show learning
      related changes in the hippocampal activity. When the training was switched to
      the 300-ms interstimulus interval trace conditioning, both groups learned above
      80% CR. The EC-lesioned animals, however, showed less learning-related activity
      in the hippocampus than the sham-operated animals. These results suggest that the
      development of the learning-related activity in the hippocampus depends on the
      intact EC, and that the EC may provide a possible pathway conveying learning
      information from the cerebellum or cerebral cortex to the hippocampus during the
      trace conditioning.

PMID- 11222055
TI  - Effects of excitotoxic brain lesions on taste-mediated odor learning in the rat.
AB  - The association learning between taste and odor is important in ingestive
      behavior. For a better understanding of this learning, we have developed a
      convenient and useful paradigm to assess the taste-mediated odor learning. In the
      training session, Wistar male rats drank water from two bottles in their home
      cages and from eight small glass dishes. In the learning session they were
      exposed in their home cages and also in a circular open-field apparatus to 0.005
      M Na-saccharin and 0.02 M quinine hydrochloride which contained either banana or
      almond odors. One learning trial consisted of this pair of exposures. The
      preceding behavioral experiment has shown that these two odors are not aversive
      and are differentially perceived by rats. In the test session, the animals were
      put in the open-field apparatus equipped with eight dishes: four contained water
      with banana, and another four, with almond. Normal control rats preferred to
      drink water with the odor previously associated with saccharin. Stronger and more
      persistent preference was attained after two or three learning trials. To
      elucidate the brain sites responsible for this taste-mediated odor learning, the
      same procedure was assessed on brain-lesioned rats. Rats with lesions in the
      amygdala showed rapid extinction of preference to the saccharin-associated odor,
      whereas control rats did not. However, rats with lesions in the insular cortex
      showed retention of learning similar to that of the control rats. Rats with
      lesions in the sulcal prefrontal or cingulate cortices showed moderate disruptive
      effects on preference to the saccharin-associated odor. In conclusion, the odor
      learning established in our experimental paradigm is based on the association
      between the quality of odor and hedonics of taste. The amygdala may play a role
      in the formation, at least in the retention process, of this taste-odor
      association learning.

PMID- 11222057
TI  - Calcitonin gene-related peptide released within the amygdala is involved in
      Pavlovian auditory fear conditioning.
AB  - The effects of CGRP and the CGRP receptor antagonist hCGRP(8-37) injected into
      the amygdala on both the acquisition and expression of fear behavior to a
      discrete auditory conditional stimulus (CS) and the training context were
      assessed. In Experiment 1, pretraining injections of CGRP but not hCGRP(8-37)
      produced fear-like behavior before any aversive stimuli were presented. While
      both compounds attenuated freezing to the contextual CS on the test day, neither
      affected learning about the auditory CS. In Experiment 2, pretesting injections
      of hCGRP(8-37) (0.63 mM) selectively attenuated freezing to the auditory CS but
      left freezing to the contextual CS intact. These data suggest that CGRP in the
      amygdala may selectively contribute to the expression of learning about auditory
      stimuli during fear conditioning.

PMID- 11222056
TI  - Comparability of a single-trial passive avoidance learning task in the young
      chick across different laboratories.
AB  - The discrepant results noted by the La Trobe/Monash, Sussex, Open, and Berkeley
      University memory research groups employing the passive avoidance task (PAT) with
      the chick indicate that some of these differences may be due to differences in
      training procedures between the various groups. The procedures employed by each
      group were replicated as closely as possible and compared using the same strain
      of chick. Higher levels of pecking and lower training latencies were observed in
      the La Trobe/Monash chicks. Improved training latency was observed following a
      change in the day of experimentation with Sussex chicks, and in white light in
      Open chicks. A powerful reinforcing effect was observed when pretraining was
      conducted with a wet lure across multiple pretraining trials, indicating the
      importance of this difference between groups. The observed impact on chick
      performance of these variables indicates that differences between PAT procedures
      may have important interactive effects with aversive learning. The results of
      data gathered using different procedures may only be superficially comparable,
      and further investigation of the effects of these variables is indicated.

PMID- 11222058
TI  - Place and response learning of rats in a Morris water maze: differential effects
      of fimbria fornix and medial prefrontal cortex lesions.
AB  - The question examined in this study is concerned with a possible functional
      dissociation between the hippocampal formation and the prefrontal cortex in
      spatial navigation. Wistar rats with hippocampal damage (inflicted by a bilateral
      lesion of the fimbria fornix), rats with damage to the medial prefrontal cortex,
      and control-operated rats were examined for their performance in either one of
      two different spatial tasks in a Morris water maze, a place learning task
      (requiring a locale system), or a response learning task (requiring a taxon
      system). Performance of the classical place learning (allocentric) task was found
      to be impaired in rats with lesions of the fimbria fornix, but not in rats with
      damage of the medial prefrontal cortex, while the opposite effect was found in
      the response learning (egocentric) task. These findings are indicative of a
      double functional dissociation of these two brain regions with respect to the two
      different forms of spatial navigation. When the place learning task was modified
      by relocating the platform, the impairment in animals with fimbria fornix lesions
      was even more pronounced than before, while the performance of animals with
      medial prefrontal cortex lesions was similar to that of their controls. When the
      task was again modified by changing the hidden platform for a clearly visible one
      (visual cue task), the animals with fimbria fornix lesions had, at least
      initially, shorter latencies than their controls. By contrast, in the animals
      with medial prefrontal cortex damage this change led to a slight increase in
      escape latency.

PMID- 11222059
TI  - Glucose treatment reduces memory deficits in young adult rats fed high-fat diets.
AB  - Feeding rats high-fat diets for 3 months produces a widespread cognitive deficit
      that affects performance on a wide range of learning and memory tasks. The
      present study tested the hypothesis that this effect is related to a fat-induced
      impairment in glucose metabolism. Following 3 months of dietary intervention (20%
      by weight fat diets, composed primarily of either beef tallow or soybean oil
      versus standard laboratory chow), male Long-Evans rats were tested on a variable
      interval delayed alternation (VIDA) task that measures learning and memory
      functions that differentially involve specific brain regions. Relative to rats
      fed chow, rats consuming the high-fat diets were impaired on all aspects of VIDA
      performance. Following baseline testing, rats were maintained on their respective
      diets and the effect of glucose administration (100 mg/kg BW; i.p.) was examined.
      For the next 6 days, animals alternately received injections of saline or glucose
      30 min prior to VIDA testing. Glucose treatment improved performance, with the
      effect being most pronounced at the longer intertrial intervals where task
      performance is sensitive to hippocampal impairment. Importantly, the beneficial
      effect of glucose were confined to those animals consuming the high-fat diets and
      were not observed in rats fed chow. These results demonstrate that glucose
      administration can overcome those deficits associated with hippocampal function
      in rats fed high-fat diets and are consistent with the hypothesis that high-fat
      diets, in part, mediate their effect through the development of insulin
      resistance and glucose intolerance.

PMID- 11222060
TI  - Effect of neonatal dentate gyrus lesion on allothetic and idiothetic navigation
      in rats.
AB  - Goal-directed navigation is believed to be the combined product of idiothetic and
      allothetic orientation. Although both navigation systems require the hippocampal
      formation, it is probable that different circuits implement them. Examination of
      Long-Evans rats with dentate gyrus lesions induced by neonatal X-ray irradiation
      may show the dissociation of these two components of navigation. Two recently
      developed place avoidance tasks on a rotating circular arena were used to test
      this hypothesis. In the first test, the position of the punished area is stable
      in the room frame but is permanently changing on the surface of the arena. This
      task requires the rat to use allothetic orientation and to disregard idiothetic
      orientation. In the second test, the prohibited area is fixed in the coordinate
      system of the arena and the experiment is conducted in complete darkness, forcing
      the rat to rely exclusively on idiothesis supported by substratal cues. The
      results suggest that the dentate gyrus lesion interferes less with idiothetic
      orientation than with allothetic orientation. In addition, an attempt was made to
      control the number of developing granule cells by exact timing of a single high
      dose of perinatal irradiation, and to measure the ensuing behavioral deficits.
      Rats irradiated at 6, 18, or 24 h after birth were tested as adults in the Morris
      water maze. Irradiated animals showed significant, but highly variable, learning
      deficit, but histological examination indicated that the granule cell loss did
      not correlate with the degree of behavioral impairment.

PMID- 11222061
TI  - A behavioral study of alpha-1b adrenergic receptor knockout mice: increased
      reaction to novelty and selectively reduced learning capacities.
AB  - Knockout mice lacking the alpha-1b adrenergic receptor were tested in behavioral
      experiments. Reaction to novelty was first assessed in a simple test in which the
      time taken by the knockout mice and their littermate controls to enter a second
      compartment was compared. Then the mice were tested in an open field to which
      unknown objects were subsequently added. Special novelty was introduced by moving
      one of the familiar objects to another location in the open field. Spatial
      behavior and memory were further studied in a homing board test, and in the water
      maze. The alpha-1b knockout mice showed an enhanced reactivity to new situations.
      They were faster to enter the new environment, covered longer paths in the open
      field, and spent more time exploring the new objects. They reacted like controls
      to modification inducing spatial novelty. In the homing board test, both the
      knockout mice and the control mice seemed to use a combination of distant visual
      and proximal olfactory cues, showing place preference only if the two types of
      cues were redundant. In the water maze the alpha-1b knockout mice were unable to
      learn the task, which was confirmed in a probe trial without platform. They were
      perfectly able, however, to escape in a visible platform procedure. These results
      confirm previous findings showing that the noradrenergic pathway is important for
      the modulation of behaviors such as reaction to novelty and exploration, and
      suggest that this is mediated, at least partly, through the alpha-1b adrenergic
      receptors. The lack of alpha-1b adrenergic receptors in spatial orientation does
      not seem important in cue-rich tasks but may interfere with orientation in
      situations providing distant cues only.

PMID- 11222062
TI  - Learning and memory in S100-beta transgenic mice: an analysis of impaired and
      preserved function.
AB  - S100-beta, a calcium-binding astrocytic protein from chromosome 21, has been
      implicated in CNS function generally and the hippocampus in particular. Elevated
      levels of S100-beta have been observed reliably in the brains of patients with
      Alzheimer's Disease and Down Syndrome. Groups of transgenic mice, carrying
      multiple S100-beta gene copies, and nontransgenic controls were administered a
      series of behavioral tests (delayed spatial and nonspatial non-matching-to
      sample, radial arm maze, socially acquired food preference) that assessed a wide
      range of cognitive functions. Consistent with the widespread presence of S100
      beta throughout the brain, transgenic mice exhibited learning or memory
      impairment on all tasks. The dementia-like cognitive profile of S100-beta mice
      represents a promising model for studying comparable cognitive deficits
      associated with neurodegenerative diseases.

PMID- 11222063
TI  - Immediate CT pneumocolon for failed colonoscopy; comparison with routine
      pneumocolon.
AB  - AIM: To assess the role and reliability of 2D CT pneumocolon in the diagnosis of
      colonic malignancy, and compare feasibility of referral sources. MATERIALS AND
      METHODS: A prospective study of 50 patients with suspected large bowel
      malignancy. Patients underwent bowel cleansing, rectal air insufflation and
      contrast enhanced CT with 5 mm collimation, 3 mm reconstruction and a pitch of
      1.4. Subsequent correlation was with pathology (16), colonoscopy (13), barium
      enema (5), ERCP (1) and clinical follow-up alone (8). RESULTS: Diagnostic images
      were obtained in 43/50 patients (86% feasibility). Follow-up was obtained in
      35/43 patients (one patient died of an unrelated cause, and seven patients were
      deemed unfit for further investigation). Seventeen colonic carcinomas were
      diagnosed (three false-positives: one ischaemic colitis, one diverticular
      stricture and one faecal mass), one diverticular stricture, one fistula, one
      pancreatic carcinoma and one ovarian malignancy. The remaining 14 were negative.
      Overall sensitivity was 100% (for lesions >1.5 cm) with a specificity of 94% for
      structural abnormalities, but only 82% for the correct identification of
      malignancy. CONCLUSION: Computed tomography (CT) pneumocolon is a reliable
      alternative to barium enema where colonoscopy is incomplete, with the advantage
      of extraluminal screening, and examination of the proximal bowel. In the frail
      elderly or young unfit patient, it is a valuable additional diagnostic tool.

PMID- 11222064
TI  - The assessment of irradiated bladder carcinoma using dynamic contrast-enhanced MR
      imaging.
AB  - AIM: To evaluate the role of dynamic contrast-enhanced magnetic resonance imaging
      (DCEMRI) in distinguishing residual or recurrent tumour from radiation change in
      patients with bladder carcinoma. MATERIALS AND METHODS: Forty patients with
      biopsy proven bladder carcinoma were imaged before and at 4 and 12 months after
      radiotherapy (XRT) using conventional and dynamic contrast-enhanced magnetic
      resonance imaging at 0.5 Tesla. An enhancement of >1.54 times above baseline at
      80 s post-contrast injection proved a reliable indicator of tumour before
      radiotherapy and was therefore applied to the assessment of patients after XRT.
      Conventional MR images and dynamic enhancement profiles (DEPs) from the site of
      previous tumour were scored by three radiologists for the presence of tumour at 4
      and 12 months after XRT. Findings were compared with cystoscopic biopsy. RESULTS:
      Dynamic contrast-enhanced magnetic resonance imaging had negative predictive
      values of 100% and 93% for tumour recurrence at 4 and 12 months, respectively.
      The positive predictive values, sensitivity and specificity were 48, 100 and 48%
      at 4 months and 50, 80 and +76% at 12 months post XRT, respectively. CONCLUSION:
      Dynamic contrast-enhanced magnetic resonance imaging may prove reliable in
      excluding the presence of persistent or recurrent tumour up to 12 months after
      XRT.

PMID- 11222065
TI  - Radiation protection in interventional radiology.
AB  - There is growing concern regarding the radiation dose delivered during
      interventional procedures, particularly in view of the increasing frequency and
      complexity of these techniques. This paper reviews the radiation dose levels
      currently encountered in interventional procedures, the consequent risks to
      operators and patients and the dose reduction that may be achieved by employing a
      rigorous approach to radiation protection.

PMID- 11222066
TI  - Magnetic resonance imaging of femoral marrow cellularity in hypocellular
      haemopoietic disorders.
AB  - AIM: Magnetic resonance imaging (MRI) of the femora was used to investigate the
      marrow cellularity during the evolution of non-transplanted aplastic anaemia (AA)
      and hypocellular myelodysplastic syndrome (h-MDS) in order to investigate the
      relationship between this cellularity and disease progression. METHODS: Magnetic
      resonance imaging was performed in adult patients with pancytopaenia and
      hypocellular bone marrow. Coronal T1 weighted and STIR images were obtained, and
      analysed semiquantitatively. These data were compared with diagnosis, peripheral
      blood counts and bone marrow histology at diagnosis and at the time of the MRI
      examination. RESULTS: Patients were examined 2-84 months after diagnosis (median,
      16 months). In AA, 11/13 patients showed a fatty, faint or nodular pattern. In h
      MDS, the majority of the patients (10/14) had a scattered or uniform signal
      pattern. In AA, a significant correlation was found between the degree of femoral
      cellularity and disease duration. Only three cases had diffuse high signal on
      STIR: among them, one had paroxysmal nocturnal haemoglobinuria and the other
      developed acute leukaemia 3 months after MRI examination. Four patients have
      died: three with h-MDS presenting a scattered (two cases) or a uniform (one case)
      MRI signal and one with AA (with a nodular pattern) CONCLUSION: In AA, femoral
      haemopoiesis is usually not pronounced, and if present, does not contribute to
      the improvement of blood counts. In h-MDS, patients with discrete femoral
      haemopoiesis had an improvement in their blood counts with disease duration,
      similar to that found in AA. Conversely, in patients with pronounced femoral
      cellularity, blood counts remained stable or had deteriorated since diagnosis.
      This favours the hypothesis that, as is observed in MDS with a hypercellular
      marrow, scattered or uniform marrow patterns in femoral MRI are signs of more
      aggressive disease.

PMID- 11222067
TI  - 'Pseudocystic' appearance of non-Hodgkin's lymphomatous nodes: an infrequent
      finding with high-resolution transducers.
AB  - AIMS: A pseudo-cystic appearance and posterior enhancement are previously
      reported to be diagnostic sonographic features of lymph node involvement in non
      Hodgkin's lymphoma. This study was undertaken to determine whether these
      ultrasonic features remain with the use of high-resolution transducers. MATERIAL
      AND METHODS: A review of ultrasound examinations in 32 patients with proven
      lymphomatous cervical lymphadenopathy (27 non-Hodgkin's lymphoma, five Hodgkin's
      disease) was performed. A total of 95 lymph nodes were assessed for size, shape,
      posterior enhancement and internal architecture. All examinations were performed
      with the same high-resolution transducer and by the same sonologist. RESULTS:
      Lymphomatous nodes (irrespective of type) are frequently heterogeneous (68-86%),
      have a micronodular pattern (63-69%) and less commonly demonstrate posterior
      enhancement (9-26%). CONCLUSION: Using a high-resolution ultrasonic transducer,
      cervical nodes involved with lymphoma (irrespective of type) commonly demonstrate
      a heterogeneous micronodular pattern. The pseudocystic appearance of nodes with
      posterior enhancement in non-Hodgkin's nodes is seen infrequently.

PMID- 11222068
TI  - The effect of radiotherapy treatment changes on sites of relapse in stage I
      testicular seminoma.
AB  - AIM: To evaluate relapse patterns in stage I testicular seminoma related to
      changes in radiotherapy practice. METHOD: Four hundred and six patients with
      stage I testicular seminoma were treated with adjuvant radiotherapy following
      orchidectomy: 338 patients received para-aortic radiotherapy only and 68 patients
      with added risk factors had radiotherapy extended to include the pelvis. Computed
      tomograms of relapsed patients were reviewed and sites of relapse were documented
      with correlation to the radiotherapy field. RESULTS: Thirteen relapses were
      identified; 10 occurring in the para-aortic radiotherapy group (3.0% relapse
      rate) and three in the extended radiotherapy field group (4.4% relapse rate).
      Sites of relapse were; five pelvis, three mediastinum, one lung, one scapula, one
      scrotum, while one patient had multiple relapse sites including the pelvis and
      one had a tumour marker relapse with no site identified. All the pelvic relapses
      occurred in the para-aortic radiotherapy group. CONCLUSION: Pelvic relapse only
      occurred when radiotherapy had been confined to the para-aortic region. Since
      para-aortic radiotherapy achieves equivalent outcome to wider field radiotherapy
      with reduced toxicity, it is likely to become standard practice in stage I
      seminoma and pelvic relapses will therefore increase in frequency. It is
      therefore important to include pelvic imaging when relapse is suspected.

PMID- 11222069
TI  - CT diagnosis of internal mammary artery injury caused by blunt trauma.
AB  - AIM: To describe the computed tomography (CT) findings associated with active
      bleeding from the internal mammary artery (IMA) in blunt trauma victims and to
      assess complications related to IMA haemorrhage. MATERIAL AND METHODS: All cases
      of active IMA haemorrhage identified in blunt trauma patients on admission CT
      were identified from a trauma radiology data base covering 1990-1999. Computed
      tomography examinations, operative and medical records were reviewed to ascertain
      CT findings, complications, and patient outcome. The determination of active
      bleeding required CT evidence of a central contrast blush of CT density within 10
      HU of an adjacent artery surrounded by haematoma. RESULTS: Four patients with CT
      evidence of active IMA haemorrhage were identified. All cases had surgical
      confirmation of an IMA source of haemorrhage. There were three patients with
      unilateral and one patient with bilateral IMA disruption. Three patients
      exhibited clinical signs of cardiac tamponade related to compression of one or
      more cardiac chambers by the anterior mediastinal haematoma. Sudden clinical
      deterioration compatible with tamponade developed in all three patients.
      CONCLUSION: Early CT recognition of active bleeding within the chest can direct
      rapid surgical or angiographic intervention. On-going blood loss and, in
      particular, the threat of cardiac tamponade must be considered with IMA injury.

PMID- 11222070
TI  - Does anybody know how we should measure Doppler parameters in lymph nodes?
AB  - AIM: To show how currently described techniques confuse interpretation of Doppler
      indices in lymph node characterization. MATERIALS AND METHODS: The Doppler
      indices [resistivity index (RI) and pulsatility index (PI)] were obtained in 35
      malignant lymph nodes by colour duplex sonography. Each node was sampled at eight
      different sites. Data were analysed using our own method, and methods employed in
      six previous studies. RESULTS: Restistivity index values varied between 0.69 and
      0.88 and PI values ranged from 1.28 to 2.34. All but two methods produced
      different resistance indices (P < 0.05). CONCLUSION: Conflicting results are
      obtained analysing the same data using different methods. Standardized techniques
      should be agreed and employed in future studies.

PMID- 11222071
TI  - Comparison of non-breath-hold high resolution gadolinium-enhanced MRA with
      digital subtraction angiography in the evaluation on allograft renal artery
      stenosis.
AB  - AIM: The study objective was to compare the diagnostic accuracy of non-breath
      hold high resolution gadolinium-enhanced magnetic resonance angiography (Gd-MRA)
      with intra-arterial digital subtraction angiography (DSA) in the evaluation of
      allograft renal artery stenosis (ARAS). MATERIALS AND METHODS: We studied 17
      renal transplant recipients (six men, 11 women, age 34-64 years) with a systolic
      bruit in the transplant region beyond the early post-operative period. Gadolinium
      enhanced magnetic resonance angiography was performed by non-breath-hold high
      resolution 3D acquisition in the oblique coronal plane using a 256 x 512
      matrix.Digital subtraction angiography was performed with AP and oblique views
      and ARAS was graded as < or =50% or >50% diameter stenosis on the view that
      displayed the maximal narrowing. RESULTS: Digital subtraction angiography showed
      >50% stenosis in seven patients, all of whom were diagnosed correctly on Gd-MRA.
      Gadolinium-enhanced magnetic resonance angiography diagnosed two patients with
      >50% stenosis which were not confirmed on DSA. Eight patients had no or < or =50%
      stenosis on both Gd-MRA and DSA. The sensitivity and specificity of Gd-MRA in
      revealing >50% stenosis were 100% and 75%, respectively, using DSA as the gold
      standard. CONCLUSION: High resolution Gd-MRA employing a non-breath-hold
      technique is highly sensitive in the diagnosis of ARAS greater than 50%. It is
      preferred as a non-invasive screening technique to DSA in suspected ARAS.

PMID- 11222072
TI  - Post-operative lumbar spine: comparative study of TSE T2 and turbo-FLAIR
      sequences vs contrast-enhanced SE T1.
AB  - AIM: To compare turbo T2 weighted spin echo (TSE T2) and turbo-FLAIR (fluid
      attenuated inversion recovery) vs gadolinium enhanced T1 weighted spin echo (SE
      T1) sequence in the differential diagnosis between disc herniation and post
      surgical fibrosis. MATERIALS AND METHODS: Sixty-four patients who underwent
      surgical treatment for lumbar disc herniation with persistent or recurrent post
      surgical symptoms were studied with a 0.5 Tesla MR system. The sequences used
      were TSE T2, turbo-FLAIR and T1 SE with and without intravenous gadolinium DTPA.
      The enhanced T1 SE sequence was considered the gold standard. Sensitivity and
      specificity were calculated. RESULTS: The sensitivity was 100% for both TSE T2
      and turbo-FLAIR sequences. The specificity was 94% for TSE T2 and 92% for turbo
      FLAIR. Negative predictive value was 100% for both sequences and positive
      predictive value 84% and 80% for TSE T2 and turbo-FLAIR, respectively.
      CONCLUSION: Although both sequences show high sensitivity, TSE-T2 presents
      greater specificity than turbo-FLAIR as compared to enhanced T1 SE. TSE T2 also
      offers the advantage of myelographic effect. We consider that the use of rapid
      sequences may avoid the need for intravenous contrast medium in most cases,
      reserving gadolinium DTPA only to those where all the criteria for hernia or
      fibrosis are not fulfilled.

PMID- 11222073
TI  - Pre-operative detection of malignant hepatic tumours: value of combined helical
      CT during arterial portography and biphasic CT during hepatic arteriography.
AB  - AIMS: The purpose of our study was to evaluate the observer performance with
      combined helical CT during arterial portography (CTAP) and biphasic CT hepatic
      arteriography (CTHA) in the pre-operative detection of malignant hepatic tumours.
      METHODS: Computed tomography images obtained in 41 patients with suspected
      hepatic tumours were retrospectively reviewed. In a blind fashion, three off
      site, independent radiologists reviewed CTAP and early-phase CTHA combined for
      the first review, then late-phase CTHA was added for the second review.
      Statistical analysis was conducted on lesion-by-lesion and segment-by-segment
      bases; a total of 328 liver segments including 65 segments with 74 malignant
      hepatic tumours ranging in size from 5 to 100 mm (mean, 21.4 mm) were analysed.
      RESULTS: Sensitivity for detection of liver segments harbouring tumours of CTAP
      and biphasic CTHA combined (82%) was identical to that of CTAP and early-phase
      CTHA combined (82%). Specificity of CTAP and biphasic CTHA combined (93%) was
      greater than that of CTAP and early-phase CTHA combined (90%, P < 0.005). The
      mean confidence level for the 74 tumours significantly increased by adding late
      phase CTHA (P < 0.0005). The mean confidence level for 100-142 benign perfusion
      abnormalities detected with CTAP and early-phase CTHA combined significantly
      decreased by adding late-phase CTHA (P < 0.0005). CONCLUSION: By combining late
      phase CTHA with CTAP and early-phase CTHA information, the specificity for the
      detection of malignant hepatic tumours rises significantly, allowing more
      accurate preoperative tumour detection.

PMID- 11222074
TI  - Deltoid contracture: MR imaging features.
AB  - AIM: To describe the magnetic resonance imaging (MRI) features of deltoid
      contracture and compare these findings with the operative and histological
      findings and to determine the utility of MRI for diagnosis and treatment
      planning. PATIENTS AND METHODS: Retrospective review of clinical and imaging in
      six patients with deltoid contracture, as well as the operative and histological
      findings of four operated patients. RESULTS: Magnetic resonance imaging clearly
      demonstrated the intramuscular fibrous bands of the deltoid as a homogeneously
      hypointense area with distinctive margins on T1-, T2- and T2*-weighted images.
      Operative findings were exactly consistent with the findings observed by MRI.
      CONCLUSION: Deltoid contracture is best evaluated with MRI which facilitates
      visualization of the intramuscular fibrous bands being pathognomonic of this
      entity and may provide information useful in treatment planning.

PMID- 11222075
TI  - Radiologist detection of microcalcifications with and without computer-aided
      detection: a comparative study.
AB  - AIM: To compare the sensitivity and specificity of microcalcification detection
      by radiologists alone and assisted by a computer-aided detection (CAD) system.
      MATERIALS AND METHODS: Films of 106 patients were masked, randomized, digitized
      and analysed by the CAD-system. Five readers interpreted the original mammograms
      and were blinded to demographics, medical history and earlier films. Forty-two
      mammograms with malignant microcalcifications, 40 with benign microcalcifications
      and 24 normal mammograms were included. Results were recorded on a standardized
      image interpretation form. The mammograms with suspicious areas flagged by the
      CAD-system were displayed on mini-monitors and immediately re-reviewed. The
      interpretation was again recorded on a new copy of the standard form and
      classified according to six groups. RESULTS: Forty-one out of 42 (98%) malignant
      microcalcifications and 32 of 40 (80%) benign microcalcifications were flagged by
      the CAD-system. There was an average of 1.2 markers per image. The sensitivity
      for malignant microcalcifications detection by mammographers without and with the
      CAD-system ranged from 81% to 98% and from 88% to 98%, respectively. The mean
      difference without and with CAD-system was 2.2% (range 0-7%). CONCLUSION: No
      statistically significant changes in sensitivity were found when experienced
      mammographers were assisted by the CAD-system, with no significant compromise in
      specificity.

PMID- 11222076
TI  - Isolated tubal torsion: CT features.

PMID- 11222077
TI  - Cystic lymphangioma of the retroperitoneum.

PMID- 11222078
TI  - Haemangioma in the distal end of the ulna resembling aneurysmal bone cyst.

PMID- 11222079
TI  - Spiral CT diagnosis of isolated systemic supply to normal lung merging from the
      coeliac trunk.

PMID- 11222080
TI  - Testicular microlithiasis in a patient with a mediastinal germ cell tumour.

PMID- 11222081
TI  - Who should be performing routine abdominal ultrasound?

PMID- 11222082
TI  - Senile scleral plaques.

PMID- 11222083
TI  - Ozone-induced modulation of cell-mediated immune responses in the lungs.
AB  - Most pulmonary immunotoxicology studies of ambient pollutants have been broadly
      designed to discern if overall humoral or cell-mediated immunity (CMI) was
      altered; few have assessed effects on particular aspects of immune function. We
      hypothesized that effects from ozone (O3) exposure on pulmonary CMI are linked in
      part to changes in local immune cell capacities to form and/or to interact with
      immunoregulatory cytokines. Rats exposed to 0.1 or 0.3 ppm O3 4 h/day 5
      days/week, for 1 or 3 weeks were assessed for resistance to, and pulmonary
      clearance of, a subsequent Listeria monocytogenes challenge. In situ cytokine
      release and immune cell profiles were also analyzed at different stages of the
      antilisterial response. Although O3 exposure modulated CMI, effects were not
      consistently concentration- or duration-dependent. Exposure did not effect
      cumulative mortality from infection, but induced concentration-related effects
      upon morbidity onset and persistence. All 1-week exposed rats had listeric
      burdens trending higher than controls; 0.3 ppm rats displayed continual burden
      increases rather than any onset of resolution. Rats exposed for 3 weeks had no O3
      related changes in clearance. No exposure-related effect on neutrophil or
      pulmonary macrophage (PAM) numbers or percentages was noted. Bacterial burden
      analyses with respect to cell type showed that Listeria:PAM ratios in 0.3 ppm
      rats ultimately became greatest compared to all other rats. In situ IL-1alpha and
      TNFalpha levels were consistently higher in O3-exposed rats. All rats displayed
      increasing in situ IFNgamma levels as infection progressed, but no constant
      relationship was evident between IFNgamma and initial IL-1alpha/TNFalpha levels
      in O3-exposed hosts. It seems that short-term (i.e., 1 week) repeated O3
      exposures imparted more effects upon CMI than a more prolonged (i.e., 3 week)
      regimen, with effects manifesting at the level of the PAM and in the cytokine
      network responsible for immunoactivation.

PMID- 11222084
TI  - Polychlorinated biphenyl-induced effects on metabolic enzymes, AP-1 binding,
      vitamin E, and oxidative stress in the rat liver.
AB  - Environmental pollutants, such as polychlorinated biphenyls (PCBs), may induce
      drug metabolism and may be substrates for the induced metabolic enzymes. Both
      processes may lead to oxidative stress. The goal of this study was to determine
      the influence of polychlorinated biphenyls, selected as inducers and substrates
      of drug metabolism, on oxidative events within the liver over a 3-week time
      course. Male and female Sprague-Dawley rats received two ip injections per week
      of 4-chlorobiphenyl, 2,4,4'-trichlorobiphenyl, 3,4,5-trichlorobiphenyl, 3,3',4,4'
      tetrachlorobiphenyl (PCB 77), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), or
      both PCB 77 and 153 (100 micromol/kg/injection) and were euthanized at the end of
      1, 2, or 3 weeks. Hepatic cytochrome P450 1A1 (EROD) activity, DT-diaphorase
      activity, AP-1 DNA-binding activity, conjugated dienes, and alpha-tocopherol
      (vitamin E) as well as alpha-tocopheryl quinone (oxidized vitamin E) were
      determined. While the lower chlorinated biphenyls (at these doses and times)
      showed little or no effect on these oxidative stress parameters, both CYP 1A1 and
      DT-diaphorase activities were significantly increased in both male and female
      rats receiving PCB 77, a ligand for the aryl hydrocarbon receptor. In addition,
      the DNA-binding activity of the transcription factor AP-1 was increased in rats
      treated with PCB 77 or PCB 153. Within the lipid fraction there was no
      significant increase observed in conjugated diene concentrations, but there was a
      significant increase in alpha-tocopheryl quinone upon treatment with all PCBs
      tested. These data indicate that alpha-tocopheryl quinone may be a sensitive
      marker for PCB exposure and is possibly increased by a wide range of PCBs.

PMID- 11222085
TI  - Mechanisms of JP-8 jet fuel toxicity. I. Induction of apoptosis in rat lung
      epithelial cells.
AB  - JP-8 is a kerosene-based fuel widely used by the U.S. military. Various models of
      human occupational and animal exposure to JP-8 have demonstrated the potential
      for local and systemic toxicity but the mechanisms involved are unknown. The
      purpose of our investigation was to study the molecular mechanisms of JP-8
      toxicity by using an in vitro model. JP-8 exposure in a rat lung alveolar type II
      epithelial cell line (RLE-6TN) induces biochemical and morphological markers of
      apoptotic cell death: caspase-3 activation, poly(ADP-ribose) polymerase (PARP)
      cleavage, chromatin condensation, membrane blebbing, cytochrome c release from
      mitochondria, and genomic DNA cleavage into both oligonucleosomal (DNA ladder)
      and high-molecular-weight (HMW) fragments. The human histiocytic lymphoma cell
      line (U937) also responds to JP-8 with caspase-3 activation, cleavage of caspase
      substrates, including PARP, DNA-PK, and lamin B1, and degradation of genomic DNA
      with the production of HMW fragments. Caspase-3 activation and PARP cleavage also
      occur in the acute T-cell leukemia cell line (Jurkat) following treatment with JP
      8. Furthermore, Jurkat cells stably transfected with a plasmid encoding the
      antiapoptotic protein Bcl-x(L) or pretreated with the pan-caspase inhibitor Boc-d
      fmk, are relatively resistant to the cytotoxic effects of JP-8 compared to
      control cells. Finally, we demonstrate that PARP cleavage occurs in primary mouse
      thymocytes exposed to JP-8. In conclusion, our data support the hypothesis that
      apoptotic cell death is responsible at least partially for the cytotoxic effects
      of JP-8 and suggest that inhibition of the apoptotic cascade might reduce JP-8
      toxicity.

PMID- 11222086
TI  - Mechanisms of JP-8 jet fuel cell toxicity. II. Induction of necrosis in skin
      fibroblasts and keratinocytes and modulation of levels of Bcl-2 family members.
AB  - JP-8 induces apoptosis in rat lung epithelial cells, primary mouse T lymphocytes,
      Jurkat T lymphoma cells, and U937 monocytic cells (Stoica et al., 2001). Here, we
      have observed a different mechanism of cytotoxicity in human keratinocytes grown
      in culture as well as when grafted onto nude mice. At lower levels of JP-8 (80
      microg/ml; 1 x 10(-4) dilution), sufficient to induce apoptosis in other cell
      types, including lung epithelial cells (Stoica et al., 2001), no apoptosis was
      observed. At higher levels (>200 microg/ml; 2.5 x 10(-4) dilution), JP-8 is
      cytotoxic to both primary and immortalized human keratinocytes, as evidenced by
      the metabolism of calcein, as well as by morphological changes such as cell
      rounding and cell detachment. There was no evidence of activation of caspases-3, 
      7, or -8 either by enzyme activity or immunoblot analysis, and the stable
      expression of a dominant-negative inhibitor of apoptosis (FADD-DN) did not
      increase the survival of keratinocytes to JP-8. The pattern of poly(ADP-ribose)
      polymerase (PARP) cleavage was also characteristic of necrosis. PARP has been
      also been implicated in necrosis via its ability to lower levels of ATP in
      damaged cells. However, fibroblasts derived from PARP-/- mice underwent necrotic
      cell death similar to those derived from PARP+/+ mice, indicating that the
      effects of JP-8 are independent of PARP. Immunoblot analysis further revealed
      that exposure of keratinocytes to the toxic higher levels of JP-8 markedly
      downregulates the expression of the prosurvival members of the Bcl-2 family, Bcl
      2 and Bcl-x(L), and upregulates the expression of antisurvival members of this
      family, including Bad and Bak. Bcl-2 and Bcl-x(L) have been shown to preserve
      mitochondrial integrity and suppress cell death. In contrast, Bak and Bad both
      promote cell death by alteration of the mitochondrial membrane potential, in part
      by heterodimerization with and inactivation of Bcl-2 and Bcl-x(L), and either
      inducing necrosis or activating a downstream caspase program. High intrinsic
      levels of Bcl-2 and Bcl-x(L) may prevent apoptotic death of keratinocytes at
      lower levels of JP-8, while perturbation of the balance between pro- and
      antiapoptotic Bcl-2 family members at higher levels may ultimately play a role in
      necrotic cell death in human keratinocytes. Finally, when human keratinocytes
      were grafted to form a human epidermis on nude mice, treatment of these grafts
      with JP-8 revealed cytotoxicity and altered histology in vivo.

PMID- 11222088
TI  - Trimethylolpropane phosphate induces epileptiform discharges in the CA1 region of
      the rat hippocampus.
AB  - The actions of trimethylolpropane phosphate (TMPP), an ethyl bicyclophosphate
      convulsant produced during the partial pyrolysis of some phosphate ester-based
      lubricants, were tested on CA1 neurons of rat hippocampal slices using
      intracellular recording techniques. Bath application of TMPP (0.1-100 microM)
      induced spontaneous paroxysmal depolarizing shifts and the associated spontaneous
      epileptiform bursts followed by after-hyperpolarizations in 63% of neurons
      tested. The TMPP-induced epileptiform bursts were blocked by muscimol, a gamma
      aminobutyric acid A (GABA(A)) receptor agonist, diazepam (DZP), a GABA(A)
      benzodiazepine ionophore complex agonist, or baclofen, a GABA(B) receptor
      agonist. While bath application of muscimol, DZP, or baclofen suppressed
      spontaneous activity in CA1 neurons not previously exposed to TMPP, subsequent
      application of TMPP (10 microM) reversed the actions of muscimol and diazepam,
      but not baclofen. TMPP (0.1-100 microM) also induced membrane hyperpolarization
      associated with an increase in peak input resistance and inward rectification in
      33% of neurons tested or membrane depolarization associated with an increase in
      input resistance in 17% of neurons tested. In summary, TMPP induced epileptiform
      activities in hippocampal CA1 neurons. The epileptogenic effects of TMPP are
      consistent with its interaction with GABA(A)-benzodiazepine receptors.

PMID- 11222087
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin affects the number and function of murine
      splenic dendritic cells and their expression of accessory molecules.
AB  - Primary T cell-mediated immune responses are highly susceptible to suppression by
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure, yet direct effects of TCDD
      on T cells have been difficult to demonstrate. Since the activation of naive T
      cells has been shown to be initiated primarily by dendritic cells (DC), these
      cells represent a potential target for TCDD immunotoxicity. In this report, we
      have examined the influence of TCDD exposure on splenic DC phenotype and function
      in the absence of antigenic stimulation. Results showed that DC from TCDD-treated
      mice expressed higher levels of several accessory molecules including ICAM-1,
      CD24, B7-2, and CD40, whereas the expression of LFA-1 was significantly reduced.
      These effects were dose-dependent and persisted for at least 14 days after
      exposure. The effects were also dependent upon the aryl hydrocarbon receptor
      (AhR), as similar effects were observed in AhR+/+ C57Bl/6 and Balb/c mice but not
      in AhR-/- mice. When DC from TCDD-treated mice were cultured with allogeneic T
      cells, the proliferative response and production of IL-2 and IFN-gamma by the T
      cells were increased. Production of IL-12 by the DC was likewise enhanced in
      comparison to cells from vehicle-treated mice. Interestingly, however, the number
      of DC recovered from TCDD-treated mice was significantly decreased. Taken
      together, these results suggest that, in the absence of antigen, TCDD provides an
      activation stimulus to DC that may lead to their premature deletion. Since the
      survival of DC has been shown to influence the strength and duration of the
      immune response, these results suggest a possible novel mechanism for TCDD
      induced immune suppression.

PMID- 11222089
TI  - Activation and suppression of RNA silencing by plant viruses.

PMID- 11222090
TI  - The genome of the archaeal virus SIRV1 has features in common with genomes of
      eukaryal viruses.
AB  - The virus SIRV1 of the extremely thermophilic archaeon Sulfolobus has a double
      stranded DNA genome similar in architecture to the genomes of eukaryal viruses of
      the families Poxviridae, Pycodnaviridae, and Asfarviridae: the two strands of the
      32,301 bp long linear genome are covalently connected forming a continuous
      polynucleotide chain and 2029 kb long inverted repeats are present at the
      termini. Very likely it also shares with these viruses mechanisms of initiation
      of replication and resolution of replicative intermediates.

PMID- 11222091
TI  - Sp1-p53 heterocomplex mediates activation of HTLV-I long terminal repeat by 12-O
      tetradecanoylphorbol-13-acetate that is antagonized by protein kinase C.
AB  - We have previously demonstrated that 12-O-tetradecanoylphorbol-13-acetate (TPA)
      activates human T-cell leukemia virus type-I long terminal repeat (LTR) in Jurkat
      cells by a protein kinase C (PKC)-independent mechanism involving a
      posttranslational activation of Sp1 binding to an Sp1 site located within the Ets
      responsive region-1 (ERR-1). By employing the PKC inhibitor, bisindolylmaleimide
      I and cotransfecting the reporter LTR construct with a vector expressing PKC
      alpha, we demonstrated, in the present study, that this effect of TPA was not
      only independent of, but actually antagonized by, PKC. Electrophoretic mobility
      shift assays together with antibody-mediated supershift and immuno
      coprecipitation analyses, revealed that the posttranslational activation of Sp1
      was exerted by inducing the formation of Sp1-p53 heterocomplex capable of binding
      to the Sp1 site in ERR-1. Furthermore, we demonstrated that Jurkat cells contain
      both wild-type (w.t.) and mutant forms of p53 and we detected both of them in
      this complex at variable combinations; some molecules of the complex contained
      either the w.t. or the mutant p53 separately, whereas others contained the two of
      them together. Finally, we showed that the Sp1-p53 complexes could bind also to
      an Sp1 site present in the promoter of another gene such as the cyclin-dependent
      kinase inhibitor p21(WAF-1), but not to consensus recognition sequences of the
      w.t. p53. Therefore, we speculate that there might be several other PKC
      independent biological effects of TPA which result from interaction of such Sp1
      p53 complexes with Sp1 recognition sites residing in the promoters of a wide
      variety of cellular and viral genes.

PMID- 11222092
TI  - The efficacy of potent anti-retroviral drug combinations tested in a murine model
      of HIV-1 encephalitis.
AB  - Development of anti-retroviral regimens with enhanced efficacy against brain HIV
      1 is essential if viral eradication is to be achieved. To address this, a severe
      combined immune deficiency mouse model of HIV-1 encephalitis was used to assay
      the effect of protease-containing and protease-sparing drug regimens on viral
      replication in brain macrophages. Here, HIV-1-infected human monocyte-derived
      macrophages (MDM) are inoculated into basal ganglia, causing a multinucleated
      giant cell encephalitis reminiscent of human disease. Drugs were administered at
      the time of MDM inoculation and continued until sacrifice. Immunohistochemical
      tests evaluated ongoing viral replication, glial immunity, and neuronal survival.
      Treatment with ddI/d4T decreased the numbers of infected cells by 75%, while
      ddI/d4T/amprenavir or ZDV/3TC/ABC diminished infection by 98%. Triple drug
      regimens decreased astrogliosis by > or = 25%. This small-animal model may be
      used to screen drug regimens that affect ongoing HIV-1 replication within its
      brain sanctuary.

PMID- 11222093
TI  - Transmission of human papillomavirus type 11 infection by desquamated cornified
      cells.
AB  - While much is known about the human papillomavirus (HPV) productive cycle, the
      mechanisms of virion transmission from person to person are poorly understood.
      The keratinocyte is the target cell of HPV infection. As keratinocytes
      differentiate, nuclei are lost and the cornified cell envelope develops. Layers
      of these desquamated cornified cells (DCCs) are continuously shed from the
      stratum corneum. Release of HPV requires the cornified cell envelope, a normally
      very durable structure, to break apart, liberating the contents of the cell. In
      differentiated keratinocytes infected with HPV 11, the cornified cell envelope is
      abnormally thin and fragile. In this study, DCCs from HPV 11-infected genital
      epithelium were used to investigate the mechanisms of viral transmission. First,
      HPV 11-infected tissue was examined for the presence of virions by transmission
      electron microscopy. Virions were observed in the nuclei of differentiated
      keratinocytes. In addition, virions were detected in the cytoplasm of DCCs that
      had undergone nuclear dissolution. Rarely, virions were observed outside of
      cells. Next, infectivity of intact and ruptured DCCs was tested in an assay
      performed in the athymic mouse xenograft system. High-titer cesium chloride
      gradient-purified HPV 11 virions infected 100% of recovered xenografts. Using
      intact DCCs derived from HPV 11-infected tissue, 62.5% of recovered xenografts
      were infected. To test the effects of mechanical stress on infectivity, DCCs were
      ruptured by sonication and used in the infectivity assay. The infectivity rate
      increased to 90%. We conclude that DCCs serve as vehicles for efficient,
      concentrated delivery of virions in HPV 11 infection.

PMID- 11222094
TI  - Resistance to Fas-mediated apoptosis of human T-cell lines expressing human T
      lymphotropic virus type-2 (HTLV-2) Tax protein.
AB  - The susceptibility to Fas-mediated apoptosis was evaluated in seven T-cell lines
      (two infected with HTLV-2, one with HTLV-1, and four HTLV-free) as well as in
      Jurkat cells transfected with a Tax-2 expressing vector. Fas-mediated apoptosis
      was significantly reduced in the HTLV-1- and HTLV-2-infected lines in comparison
      with the HTLV-free lines regardless of the surface expression of Fas antigen
      (which was no different in the infected and uninfected cells). Fas-mediated
      apoptosis was also significantly inhibited in Jurkat cells transfected with the
      Tax-2 expressing vector without any modification in Fas expression. There was
      significantly more antiapoptotic Bcl-x(L) mRNA and protein in the transfected
      than in the untransfected Jurkat T cells. In conclusion, our results suggest that
      HTLV-2 is capable of inhibiting Fas-mediated apoptosis by means of a mechanism
      involving the tax-2 gene and probably the expression of bcl-x(L) messenger and
      protein.

PMID- 11222095
TI  - Retention of a small replicase gene segment in tomato bushy stunt virus defective
      RNAs inhibits their helper-mediated trans-accumulation.
AB  - Tomato bushy stunt virus (TBSV) and other tombusviruses are notorious for their
      propensity to accumulate defective interfering RNAs (DIs) upon serial passage
      through experimental Nicotiana species. Hallmarks of this occurrence include
      reduced levels of helper RNA and protein accumulation and amelioration of the
      lethal necrosis induced upon infection of the host with the helper viruses alone.
      The objective of this study was to determine whether the prolific trans
      accumulation of defective RNAs typically occurs for all replicase-deficient TBSV
      mutants, or if this process is influenced by internal cis-acting elements that
      have been excised from DIs. For this purpose, various replicase-deficient TBSV
      cDNA constructs were generated and their transcripts were tested for trans
      accumulation competence in the presence of helper virus. The results revealed
      that a region of ca. 150 nucleotides near the center of the replicase gene, with
      a predicted high degree of secondary structure, was a potent inhibitor of trans
      rescue (ITR) by TBSV. Relocation of the ITR into efficiently trans-replicating
      DIs inhibited their accumulation drastically, but only when inserted in the
      reverse orientation and with an intact 5' ITR-specific predicted hairpin
      structure. Insertion of the ITR element in the positive orientation yielded DI
      transcripts that were able to replicate, but failed to interfere noticeably with
      either accumulation of the helper RNA or the onset of the lethal necrosis
      phenotype in N. benthamiana. In conclusion, the ITR has an intrinsic capacity to
      inhibit trans-accumulation of defective RNAs, but its stringency and biological
      effects are strongly influenced by the overall sequence context.

PMID- 11222096
TI  - Disruption of differentiated functions during viral infection in vivo. V. Mapping
      of a locus involved in susceptibility of mice to growth hormone deficiency due to
      persistent lymphocytic choriomeningitis virus infection.
AB  - Lymphocytic choriomeningitis virus (LCMV) Armstrong strain selectively and
      persistently infects the majority of growth hormone (GH) producing cells in the
      anterior lobe of pituitary glands of C3H/St mice but negligibly infects GH
      producing cells of BALB/WEHI mice (Oldstone et al., Virology 142, 175--182, 1985;
      Oldstone et al., Science 218, 1125--1127, 1982). Although infected GH cells
      remain free of structural damage, disrupted initiation of GH transcription
      (Klavinskis and Oldstone, J. Gen. Virol. 68, 1867--1873, 1989; Valsamakis et al.,
      Virology 156, 214--220, 1987) occurs with a resultant decrease in the synthesis
      of GH, leading to a failure of growth and development (Oldstone et al., Science
      218, 1125--1127, 1982). Microsatellite mapping of DNA obtained from 101
      individual C3H/St x BALB/WEHI F1 x F1 mice shows that the growth failure
      correlates with host genes linked (P value 0.0008) on chromosome 17 just outside
      of the H-2D MHC site between D17 Mit24 and D17 Mit51, a distance of 2.5 cM. The
      genetic mapping done here excludes alpha-dystroglycan (alpha-DG), a known
      receptor for LCMV (Cao et al., Science 282, 2079--2081, 1998) in pathogenesis of
      GH disease, as alpha-DG is encoded in the mouse by a gene residing on chromosome
      9 (Yotsumoto et al., Hum. Mol. Genet. 5, 1259--1267, 1996).

PMID- 11222097
TI  - The Bunyamwera virus nonstructural protein NSs inhibits viral RNA synthesis in a
      minireplicon system.
AB  - The small (S) genomic segment of Bunyamwera virus (family Bunyaviridae, genus
      Bunyavirus) encodes the nucleocapsid protein, N, and a nonstructural protein,
      NSs, in overlapping reading frames. In order to elucidate the function of NSs, we
      established a plasmid-based minireplicon system using mammalian cells that
      express large amounts of T7 RNA polymerase. Expression of N, the viral polymerase
      protein (L), and a minireplicon containing a reporter gene was sufficient to
      reconstitute functional virus nucleocapsids. Coexpression of NSs, however, led to
      a dose-dependent decrease in reporter activity without affecting expression of
      controls. The inhibition could not be reversed by overexpression of N, L or the
      minireplicon, indicating that the NSs effect was not caused by a reduction in
      virus gene expression. The NSs proteins of two other members of the Bunyavirus
      genus, Guaroa virus and Lumbo virus, were also inhibitory in our system. The
      intracellular localisation of Bunyamwera virus NSs was investigated and found to
      be predominantly cytoplasmic, but intranuclear inclusion was also detected. Taken
      together, these data suggest that, in mammalian cells, the bunyavirus NSs protein
      controls the activity of the viral polymerase by a highly conserved mechanism.

PMID- 11222098
TI  - Genetic variation in the 3' non-coding region of dengue viruses.
AB  - The 3' non-coding region (3'NCR) of strains of dengue 1 (DEN 1), DEN 2, DEN 3,
      and DEN 4 viruses, isolated in different geographical regions, was sequenced and
      compared to published sequences of the four dengue viruses. A total of 50 DEN 2
      strains was compared: 7 West African strains, 3 Indonesian mosquito strains, 1
      Indonesian macaque isolate, and 39 human isolates from Southeast Asia, the South
      Pacific, and the Caribbean and Americas. Nucleotide sequence alignment revealed
      few deletions and no repeat sequences in the 3' NCR of DEN 2 viruses and showed
      that much of the 3' NCR was well conserved. The strains could be divided into two
      groups, sylvatic and human/mosquito/macaque, based on nucleotide sequence
      homology. A hypervariable region was identified immediately following the NS5
      stop codon, which involved a 2-10 nucleotide deletion in human, mosquito, and
      macaque isolates compared with the sylvatic strains. The DEN 2 3'NCR was also
      compared with 3'NCR sequences from strains of DEN 1, DEN 3, and DEN 4 viruses.
      DEN 1 was found to have four copies of an eight nucleotide imperfect repeat
      following the NS5 stop codon, while DEN 4 virus had a deletion of 75 nucleotides
      in the 3'NCR. We propose that the variation in nucleotide sequence in the 3'NCR
      may have evolved as a function of DEN virus transmission and replication in
      different mosquito and non-human primate/human host cycles. The results from this
      study are consistent with the hypothesis that DEN viruses arose from sylvatic
      progenitors and evolved into human epidemic strains. However, the data do not
      support the hypothesis that variation in the 3'NCR correlates with DEN virus
      pathogenesis.

PMID- 11222099
TI  - Detection and subcellular localization of the turnip yellow mosaic virus 66K
      replication protein in infected cells.
AB  - Turnip yellow mosaic virus (TYMV) encodes a 206-kDa (206K) polyprotein with
      domains of methyltransferase, proteinase, NTPase/helicase, and RNA-dependent RNA
      polymerase (RdRp). In vitro, the 206K protein has been shown to undergo
      proteolytic processing, giving rise to the synthesis of 140-kDa (140K) and 66-kDa
      (66K) proteins, the latter comprising the RdRp protein domain. Antibodies were
      raised against the 66K protein and were used to detect the corresponding viral
      protein in infected cells; both leaf tissues and protoplasts were examined. The
      antiserum specifically recognized a protein of approximately 66 kDa, indicating
      that the cleavage observed in vitro is also functional in vivo. The 66K protein
      accumulates transiently during protoplast infection and localizes to cellular
      membrane fractions. Indirect immunofluorescence assays and electron microscopy of
      immunogold-decorated ultrathin sections of infected leaf tissue using anti-66K
      specific antibody revealed labeling of membrane vesicles located at the
      chloroplast envelope.

PMID- 11222100
TI  - In vitro dissection of the membrane and RNP binding activities of influenza virus
      M1 protein.
AB  - Spontaneous proteolysis of influenza virus M1 protein during crystallisation has
      defined an N-terminal domain of amino acids 1--164. Full-length M1, the N
      terminal domain, and the C-terminal part of M1 (residues 165--252) were produced
      in Escherichia coli. In vitro tests showed that only full-length M1 and its N
      terminal domain bind to negatively charged liposomes and that only full-length M1
      and its C-terminal part bind to RNP. However, only full-length M1 had
      transcription inhibition activity. Several independent experimental approaches
      indicate that in vitro transcription inhibition occurs through
      polymerisation/aggregation of M1 onto RNP, or of M1 onto M1 already bound to RNP,
      rather than by binding to a specific active site on the nucleoprotein or the
      polymerase. The structure/function of influenza virus M1 will be compared with
      that of the Ebola virus matrix protein, VP40.

PMID- 11222101
TI  - Role of distal zinc finger of nucleocapsid protein in genomic RNA dimerization of
      human immunodeficiency virus type 1; no role for the palindrome crowning the R-U5
      hairpin.
AB  - Genomic RNA isolated from HIV-1 variously mutated in nucleocapsid protein (NC)
      was characterized by nondenaturing gel electrophoresis. Mutations in the C
      terminal, the N-terminal, and the linker regions had no effect on genomic RNA
      dimerization [they are R7R10K11S, P31L, R32G, S3(32-34), and K59L], while a
      C36S/C39S mutation in the distal zinc knuckle (Cys-His box or zinc finger)
      inhibited genome dimerization as much as disrupting the kissing-loop domain. The
      four mutations which inhibited tRNA(Lys3) genomic placement (i.e., the in vivo
      placement of tRNA(Lys3) on the primer binding site) had no effect on genome
      dimerization. Among five mutations which inhibited genome packaging, four had no
      effect on genome dimerization. Thus the N-terminal and linker regions of NC
      control genome packaging/tRNA(Lys3) placement (two processes which do not require
      mature NC) but have little influence on genome dimerization and 2-base extension
      of tRNA(Lys3) (two processes which are likely to require mature NC). It has been
      suggested, based on electron microscopy, that the AAGCUU82 palindrome crowning
      the R-U5 hairpin stimulates genomic RNA dimerization. To test this hypothesis, we
      deleted AGCU81 from wild-type viruses and from viruses bearing a disrupted
      kissing-loop hairpin or kissing-loop domain; in another mutant, we duplicated
      AGCU81. The loss of AGCU81 reduced dimerization by 2.5 +/- 4%; its duplication
      increased it by 3 +/- 6%. Dissociation temperature was left unchanged. We reach
      two conclusions. First, the palindrome crowning the R-U5 hairpin has no impact on
      HIV-1 genome dimerization. Second, genomic RNA dimerization is differentially
      influenced by NC sequence: it is Zn finger dependent but independent of the basic
      nature of the N-terminal and linker subdomains. We propose that the NC regions
      implicated in 2-base extension of tRNA(Lys3) are required for a second
      (maturation) step of tRNA placement. Genome dimerization and mature tRNA
      placement would then become two RNA-RNA interactions sharing similar NC sequence
      requirements.

PMID- 11222102
TI  - In vitro translational analysis of genomic, defective, and satellite RNAs of
      Cryphonectria hypovirus 3-GH2.
AB  - Cryphonectria hypovirus 3-GH2 (CHV3-GH2) is a member of the fungal virus family
      Hypoviridae that differs from previously characterized members in having a single
      large open reading frame with the potential to encode a protein of 326 kDa from
      its 9.8-kb genome. The N-terminal portion of the ORF contains sequence motifs
      that are somewhat similar to papain-like proteinases identified in other
      hypoviruses. Translation of the ORF is predicted to release autocatalytically a
      32.5-kDa protein. A defective RNA, predicted to encode a 91.6-kDa protein
      representing most of the N-terminal proteinase fused to the entire putative
      helicase domain, and two satellite RNAs, predicted to encode very small proteins,
      also are associated with CHV3-GH2 infected fungal cultures. We performed in vitro
      translation experiments to examine expression of these RNAs. Translation of three
      RT-PCR clones representing different lengths of the amino-terminal portion of the
      ORF of the genomic RNA resulted in autocatalytic release of the predicted 32.5
      kDa protein. Site-directed mutagenesis was used to map the processing site
      between Gly(297) and Thr(298). In vitro translation of multiple independent cDNA
      clones of CHV3-GH2-defective RNA 2 resulted in protein products of approximately
      92 kDa, predicted to be the full-length translation product, 32 kDa, predicted to
      represent the N-terminal proteinase, and 60 kDa, predicted to represent the C
      terminal two-thirds of the full-length product. In vitro translation of cDNA
      clones representing satellite RNA 4 resulted in products of slightly less than 10
      kDa, consistent with the predicted 9.4 kDa product.

PMID- 11222103
TI  - Analyzing the mechanisms of interferon-induced apoptosis using CrmA and hepatitis
      C virus NS5A.
AB  - The dsRNA-dependent protein kinase, PKR, is a key component of interferon (IFN)
      mediated anti-viral action and is frequently inhibited by many viruses following
      infection of the cell. Recently, we have demonstrated that IFN and PKR can
      sensitize cells to apoptosis predominantly through the FADD/caspase-8 pathway (S.
      Balachandran, P. C. Roberts, T. Kipperman, K. N. Bhalla, R. W. Compans, D. R.
      Archer, and G. N. Barber. (2000b) J. Virol. 74, 1513-1523). Given these findings,
      it is thus plausible that rather than specifically target IFN-inducible genes
      such as PKR, viruses could also subvert the mechanisms of IFN action, in part, at
      locations that could block the apoptotic cascade. To explore this possibility, we
      analyzed whether the poxvirus caspase-8 inhibitor, CrmA, was able to inhibit IFN
      or PKR/dsRNA-mediated apoptosis. Our findings indicated that CrmA could indeed
      inhibit apoptosis induced by both viral infection and dsRNA without blocking PKR
      activity or inhibiting IFN signaling. In contrast HCV-encoded NS5A, a putative
      inhibitor of PKR, did not appear to inhibit cell death mediated by a number of
      apoptotic stimuli, including IFN, TRAIL, and etoposide. Our data imply that viral
      encoded inhibitors of apoptosis, such as CrmA, can block the innate arms of the
      immune response, including IFN-mediated apoptosis, and therefore potentially
      constitute an alternative family of inhibitors of IFN action in the cell.

PMID- 11222104
TI  - Paramyxovirus fusion (F) protein: a conformational change on cleavage activation.
AB  - The fusion (F) protein of the paramyxovirus SV5 promotes both virus-cell and cell
      cell fusion. Recently, the atomic structure at 1.4 A of an extremely thermostable
      six-helix bundle core complex consisting of two heptad repeat regions of the F
      protein has been described (K. A. Baker, R. E. Dutch, R. A. Lamb, and T. S
      Jardetsky, Mol. Cell 3, 309-319, 1999). To analyze the conformations of the F
      protein at various stages of the membrane fusion process and to understand
      further the role of formation of the six-helix bundle core complex in promotion
      of membrane fusion, antibodies to peptides corresponding to regions of the F
      protein were obtained. Major changes in F protein antibody recognition were found
      after cleavage of the precursor protein F(0) to the fusogenically active
      disulfide-linked heterodimer, F(1) + F(2), and antibodies directed against the
      heptad repeat regions recognized only the uncleaved form. A monoclonal antibody
      directed against the F protein showed increased recognition at the cell surface
      of the cleaved form of the F protein as compared to uncleaved F protein, again
      indicating changes in conformation between the uncleaved and cleaved forms of the
      F protein. Anti-peptide antibodies specific for the heptad repeat regions were
      unable to precipitate a synthetic protein that consisted of the heptad repeat
      regions separated only by a small spacer, suggesting that the antibodies are
      unable to recognize their target regions when the heptad repeats are present in
      the six-helix bundle core complex. Taken together, these data indicate that the
      six-helix bundle core complex is not present in the precursor molecule F(0) and
      that significant conformational changes occur subsequent to cleavage of the F
      protein.

PMID- 11222105
TI  - Limitations of chromosome classification by multicolor karyotyping.
AB  - Multicolor karyotyping technologies, such as spectral karyotyping (SKY) (Schrock
      et al.1996; Liyanage et al. 1996) and multiplex (M-) FISH (Speicher et al. 1996),
      have proved to be extremely useful in prenatal, postnatal, and cancer
      cytogenetics. However, these technologies have inherent limitations that, in
      certain situations, may result in chromosomal misclassification. In this report,
      we present nine cases, which fall into five categories, in which multicolor
      karyotyping has produced erroneous interpretations. Most errors appear to have a
      similar mechanistic basis.

PMID- 11222106
TI  - Linkage analysis of a complex pedigree with severe bipolar disorder, using a
      Markov chain Monte Carlo method.
AB  - Recently developed algorithms permit nonparametric linkage analysis of large,
      complex pedigrees with multiple inbreeding loops. We have used one such
      algorithm, implemented in the package SimWalk2, to reanalyze previously published
      genome-screen data from a Costa Rican kindred segregating for severe bipolar
      disorder. Our results are consistent with previous linkage findings on chromosome
      18 and suggest a new locus on chromosome 5 that was not identified using
      traditional linkage analysis.

PMID- 11222107
TI  - Evaluation of pulmonary alveolar epithelial integrity by the detection of
      restriction to diffusion of hydrophilic solutes of different molecular sizes.
AB  - The rate of transfer of a hydrophilic solute from the alveoli to pulmonary blood
      following inhalation as an aerosol depends on the molecular size of the solute
      and the permeability of the alveolar epithelium. The value of this measurement
      for assessing damage to the epithelium in lung disease is compromised by
      cigarette smoking, which accelerates clearance by unknown mechanisms. The rates
      of clearance of (99m)Tc-labelled diethylenetriaminepenta-acetic acid (DTPA)
      (molecular mass 492 Da) and (113m)In-labelled biotinylated DTPA (B-DTPA)
      (molecular mass 1215 Da) were monitored simultaneously by dynamic gamma-radiation
      camera imaging following simultaneous inhalation, and compared between eight
      normal non-smoking subjects and nine habitual cigarette smokers. The clearance
      rates of DTPA were 0.95 (S.D. 0.39)%/min in non-smokers and 4.13 (1.06) %/min in
      smokers. These were about twice the clearance rates of B-DTPA, which in the
      corresponding groups were 0.41 (0.26) and 2.12 (0.72)%/min respectively. The
      ratio of the B-DTPA/DTPA clearance rates was, in all subjects, less than the
      ratio (0.74) of the cube roots of the molecular masses of the solutes, assumed to
      correspond to the ratio of their free diffusion coefficients in water, and was
      not significantly different between smokers and non-smokers. As alveolar
      permeability increased, the ratio of clearance rates in the entire population
      showed a significant trend to increase in a non-linear fashion towards the value
      corresponding to the ratio of the free diffusion coefficients. We conclude that
      the diffusion of at least the larger of these two solutes through the pulmonary
      alveolar epithelium is restricted (i.e. associated with a reflection coefficient
      greater than zero). Cigarette smoking, however, does not appear to cause a loss
      of this restriction, and may increase solute clearance by other mechanisms, such
      as reducing fluid volume within the alveolus, thereby raising the local
      radiotracer concentration, or increasing the number of pores available for solute
      exchange without affecting pore size. Conversely, if restriction was lost in lung
      disease, the ratio of the clearance rates of two solutes of dissimilar sizes
      could be used to detect disease in smokers as well as non-smokers.

PMID- 11222108
TI  - Does free extracellular iron exist in haemochromatosis and other pathologies, and
      is it redox active?

PMID- 11222109
TI  - A simple, highly sensitive and improved method for the measurement of bleomycin
      detectable iron: the 'catalytic iron index' and its value in the assessment of
      iron status in haemochromatosis.
AB  - In the presence of ferrous ions (Fe(2+)), the anti-tumour agent bleomycin will
      induce DNA degradation. Degradation of DNA into substances detectable by the
      thiobarbituric acid test has been used previously for the detection of iron in a
      form that is capable of catalysing the formation of the potentially harmful
      hydroxyl free radical. In the present paper, we describe the application of the
      ethidium-binding assay of DNA damage to the measurement of bleomycin-detectable
      iron, comparing its performance with the conventional method in the assessment of
      iron standard solutions and plasma samples from haemochromatosis patients. The
      ethidium-binding assay proved to be more responsive than the thiobarbituric acid
      test in the detection of DNA damage induced by very low concentrations of iron,
      but became saturated at higher iron concentrations. Agreement between the two
      versions of the assay in the identification of plasma samples containing
      bleomycin-detectable iron was good, but agreement on the actual concentrations of
      such iron in the positive samples was poor. This discrepancy is believed to be
      due to interference with the thiobarbituric acid assay by plasma. Consequently,
      it was not possible to obtain reliable estimates of free iron concentrations in
      plasma when using the conventional version of the bleomycin assay. We have
      devised a parameter of iron status called the catalytic iron index. For healthy,
      non-haemochromatotic individuals, the mean value of this parameter was found to
      be 0.81 (range 0.78-0.84; n=20). Elevated values were observed in some plasma
      samples from haemochromatosis patients, but these showed no correlation with
      serum ferritin levels. In contrast, correlations were seen with both serum iron
      and transferrin saturation levels, but only when these were above the normal
      range.

PMID- 11222110
TI  - Aminoguanidine and ramipril prevent diabetes-induced increases in protein kinase
      C activity in glomeruli, retina and mesenteric artery.
AB  - This study investigated the effects of insulin therapy, inhibition of advanced
      glycation end-product formation with aminoguanidine and angiotensin-converting
      enzyme inhibition with ramipril on diabetes-related increases in protein kinase C
      (PKC) activity in the streptozotocin-diabetic rat. PKC activity in the glomeruli,
      retina and mesenteric artery was increased by 1.5-2-fold after induction of
      diabetes, and this increase was maintained over 24 weeks. Treatment with insulin
      at 2 units or 6 units per day attenuated glomerular PKC in proportion to the
      level of glycohaemoglobin after 4 weeks of diabetes (r=0.68, P<0.0001). The
      higher dose of insulin prevented the diabetes-related increase in glomerular PKC
      activity, although blood glucose levels were not normalized. After 8 weeks of
      diabetes, ramipril completely prevented the diabetes-related increases in PKC
      activity in the glomeruli, retina and mesenteric artery. By contrast,
      aminoguanidine treatment resulted in no inhibition of glomerular PKC activity,
      partial inhibition of retinal PKC activity and complete inhibition of mesenteric
      artery PKC activity. After 24 weeks of diabetes, both aminoguanidine and ramipril
      prevented the diabetes-related increases in PKC activity in all three tissues, in
      parallel with suppression of albuminuria by both agents. Aminoguanidine also
      prevented diabetes-related increases in retinal permeability at 16 weeks. These
      results suggest that the organ-protective effects of insulin, aminoguanidine and
      ramipril in diabetes may be mediated, at least in part, through the differential
      inhibition of PKC activity in various tissues.

PMID- 11222111
TI  - Post-transcriptional effects of extracellular pH on tumour necrosis factor-alpha
      production in RAW 246.7 and J774 A.1 cells.
AB  - The present studies determined the effects of extracellular pH (pH(o)) on the
      production of tumour necrosis factor-alpha (TNF-alpha) in the macrophage-like
      cell lines RAW 246.7 and J774 A.1. The cells were activated with
      lipopolysaccharide (LPS) at pH(o) 5.5, 6.5 or 7.4. TNF-alpha gene transcription
      was monitored by Northern blot analysis. Synthesis of the cytokine was monitored
      by ELISA measurements of the TNF-alpha content of cell-conditioned media
      (extracellularly released TNF-alpha) and cell lysates (cytosolic TNF-alpha). The
      magnitude of the TNF-alpha response differed markedly between the two cell lines.
      RAW cells were more responsive to LPS than were J774 cells. However, the effects
      of pH(o) on TNF-alpha production were similar in the two cell lines. TNF-alpha
      gene transcription was insensitive to experimental pH(o). The pH(o) had no effect
      on the abundance of TNF-alpha mRNA at 2, 4 or 18 h. Nonetheless, synthesis of TNF
      alpha was affected significantly by pH(o). The TNF-alpha contents of cell
      conditioned medium and cell lysate at 18 h were reduced progressively at lower
      pH(o) values. The data indicate that pH(o) alters TNF-alpha production in RAW and
      J774 cells at a post-transcriptional level. These findings suggest that pH(o)
      influences the phenotypic responses of macrophages to activating stimuli and
      modifies the role that macrophages play in inflammatory and immune actions.

PMID- 11222112
TI  - Influence of aging on cardiac baroreflex sensitivity determined non-invasively by
      power spectral analysis.
AB  - Aging reduces cardiac baroreflex sensitivity. Our primary aim in the present
      study was to assess the effects of aging on cardiac baroreflex sensitivity, as
      determined by power spectral analysis (alpha index), in a large population of
      healthy subjects. We also compared the alpha indexes determined by power spectral
      analysis with cardiac baroreflex sensitivity measured by the phenylephrine method
      (BS(phen)). We studied 142 subjects (79 males/63 females; age range 9-94 years),
      who were subdivided into five groups according to percentiles of age (25, 50, 75
      and 95). Power spectral analysis yields three alpha indexes: an alpha low
      frequency (LF) index of cardiac baroreflex sensitivity that ranges around 0.1 Hz;
      an alpha high-frequency (HF) index reflecting cardiac baroreflex sensitivity
      corresponding to the respiratory rate; and alpha total frequency (alpha TF), a
      new index whose spectral window includes all power in the range 0.03-0.42 Hz.
      Spectra were recorded during controlled and uncontrolled respiration. Under both
      conditions, all three alpha indexes were higher in the youngest age group (< or
      =34 years old) than in the three oldest groups. Notably, alpha TF was
      significantly higher in younger subjects than in the three oldest groups [14+/-1
      ms/mmHg compared with 9+/-1 (P<0.05), 8.1+/-1 (P<0.001) and 8.1+/-1 (P<0.05)
      ms/mmHg respectively]. BS(phen) showed a similar pattern [12+/-1 ms/mmHg compared
      with 8+/-0.5 (P<0.001), 6+/-0.5 (P<0.05) and 6+/-1 (P<0.05) ms/mmHg
      respectively]. No significant differences were found for cardiac baroreflex
      sensitivity among the three oldest groups. All alpha indexes were correlated
      inversely with age. The index yielding the closest correlation with BS(phen) was
      alpha TF (r=0.81, P<0.001). Cardiac baroreflex sensitivity in normotensive
      individuals declines with age. It falls predominantly in middle age (from approx.
      48 years onwards) and remains substantially unchanged thereafter. The elderly
      subjects we selected for this study probably had greater resistance to
      cardiovascular disease that is manifested clinically, with preserved cardiac
      baroreceptor sensitivity.

PMID- 11222113
TI  - Role of GADD153 (growth arrest- and DNA damage-inducible gene 153) in vascular
      smooth muscle cell apoptosis.
AB  - GADD153 (growth arrest- and DNA damage-inducible gene 153) is expressed at very
      low levels in growing cells, but is markedly induced in response to a variety of
      cellular stresses, including glucose deprivation, exposure to genotoxic agents
      and other growth-arresting situations. Forced expression of GADD153 induces cell
      cycle arrest in many types of cells. It is also reported that GADD153 is directly
      associated with apoptosis. Recently we have reported that platelet-derived growth
      factor (PDGF)-BB induces apoptosis in cultured vascular smooth muscle cells
      (VSMC), but only when 100% confluency is reached. These results suggested that
      cell-cell contact inhibition (cell growth arrest) may be a critical factor for
      induction of VSMC apoptosis by PDGF-BB. In the present study, we explored the
      role of GADD153, one of a number of growth-arrest-related gene products, in the
      molecular mechanisms of VSMC apoptosis in vitro and in vivo. GADD153 was markedly
      induced at both the mRNA and protein levels, in parallel with the induction of
      VSMC apoptosis, after treatment with PDGF-BB. Moreover, overexpression of GADD153
      in VSMC significantly reduced cell viability and induced apoptosis. In the
      carotid artery balloon injury model in rats, GADD153 protein was expressed in
      apoptotic VSMC which were positively stained by in situ DNA labelling. These
      results demonstrate an important role for GADD153 in the molecular mechanisms of
      VSMC apoptosis.

PMID- 11222114
TI  - Insulin stimulates laser Doppler signal by rat muscle in vivo, consistent with
      nutritive flow recruitment.
AB  - Insulin-mediated increases in limb blood flow are thought to enhance glucose
      uptake by skeletal muscle. Using the perfused rat hindlimb, we report that macro
      laser Doppler flowmetry (LDF) probes positioned on the surface of muscle detect
      changes in muscle capillary (nutritive) flow. With this as background, we
      examined the effects of insulin and adrenaline (epinephrine), which are both
      known to increase total leg blood flow, on the LDF signals from scanning and
      stationary probes on the muscle surface in vivo. The aim is to assess the
      relationship between capillary recruitment, total limb blood flow and glucose
      metabolism. Glucose infusion rate, femoral arterial blood flow (FBF) and muscle
      LDF, using either scanning or a stationary probe positioned over the biceps
      femoris muscle, were measured. With scanning LDF, animals received insulin (10 m
      units x min(-1) x kg(-1)), adrenaline (0.125 microg.min(-1) x kg(-1)) or saline.
      By 1 h, insulin had increased the glucose infusion rate from 0 to 128
      micromol.min(-1) x kg(-1) and the scanning LDF had increased by 62+/-8% (P<0.05),
      but FBF was unaffected. Adrenaline increased FBF by 49% at 15 min, but LDF was
      unchanged. With saline at 1 h, neither FBF nor LDF had changed. With the
      stationary LDF surface probe, insulin at 1 h had increased FBF by 47% (P<0.05)
      and LDF by 47% (P<0.05) relative to saline controls. Adrenaline increased FBF
      (39%), but LDF was unaltered. The stimulation of LDF by insulin is consistent
      with capillary recruitment (nutritive flow) as part of the action of this hormone
      in vivo. The recruitment may be independent of changes in total flow, as
      adrenaline, which also increased FBF, did not increase LDF. The time of onset
      suggests that LDF closely parallels glucose uptake. Thus, depending on probe
      design, measurement of muscle haemodynamic effects mediated by insulin in
      normally responsive and insulin-resistant patients should be possible.

PMID- 11222115
TI  - Peroral immunization with Helicobacter pylori adhesin protein genetically linked
      to cholera toxin A2B subunits.
AB  - Helicobacter pylori is a major cause of gastric-associated diseases. To evaluate
      the efficacy of a possible vaccine antigen against H. pylori infection, the
      chimaeric construct adhesin--CTXA2B, derived from H. pylori adhesin genetically
      coupled to cholera toxin (CTX) subunits A2 and B (CTXA2B), was expressed in
      Escherichia coli as an insoluble recombinant chimaeric protein. The protein was
      then purified by denaturation, renaturation and size-exclusion chromatography.
      The composition of purified adhesin--CTXA2B was verified by SDS/PAGE and Western
      blotting with antibodies to antigenic components of adhesin and CTXB, and
      confirmed as a chimaeric protein with G(M1)-ganglioside binding activity and
      adhesin epitopes by a G(M1)-ELISA developed using antibodies to adhesin. Oral
      immunization of mice with adhesin--CTXA2B induced higher levels of mucosal IgA
      and serum IgG antibodies to H. pylori adhesin and to CTXB than in mice immunized
      with adhesin or CTXA2B alone. Adhesin--CTXA2B was also demonstrated to be a
      potential protective antigen in a mouse model of H. pylori infection. The
      immunization of mice with adhesin--CTXA2B protected 62.5% of mice infected with
      H. pylori SS1 strain, whereas adhesin immunization was not able to confer
      protection to mice. This protection may be correlated with high levels of mucosal
      IgA and serum IgG antibodies against H. pylori adhesin. Taken together, the
      results indicate that the genetically linked CTXA2B acts as a useful mucosal
      adjuvant, and that the adhesin-CTXA2B chimaeric protein could be a potential
      component in future H. pylori vaccine development.

PMID- 11222116
TI  - Muscle glutamine production in burn patients: the physiological meaning of tracer
      estimates.

PMID- 11222117
TI  - Attenuated cardiac baroreflex in men with presyncope evoked by lower body
      negative pressure.
AB  - Mechanisms responsible for presyncope during lower body negative pressure (LBNP)
      in otherwise healthy subjects are poorly understood. Muscle sympathetic nerve
      activity (MSNA), blood pressure, heart rate (HR), HR power spectra, central
      venous pressure (CVP) and stroke volume were determined in 14 healthy men
      subjected to incremental LBNP. Of these, seven experienced presyncope at LBNP >
      15 mmHg. Subjects who tolerated LBNP >-15 mmHg had significantly lower CVP (2.6+/
      1.0 versus 7.2+/-1.2 mmHg; means+/-S.E.M., P<0.02), HR (59+/-2 versus 66+/-3
      beats/min, P<0.05) and MSNA burst frequency (29.0+/-2.4 versus 39.0+/-3.5
      bursts/min, P<0.05) during supine rest. LBNP at -15 mmHg had no effect on blood
      pressure, but caused similar and significant reductions in stroke volume and
      cardiac output in both groups. Subjects who tolerated LBNP had significant reflex
      increases in HR, MSNA burst frequency and burst amplitude with LBNP of -15 mmHg.
      These responses were absent in those who experienced presyncope. The gain of the
      cardiac baroreflex regulation of MSNA was markedly attenuated in pre-syncopal
      subjects (1.2+/-0.6 versus 8.8+/-1.4 bursts/100 heart beats per mmHg; P<0.001).
      Healthy subjects who experience presyncope in response to LBNP appear more
      dependent, when supine, upon MSNA to maintain preload, and less able to increase
      sympathetic vasoconstrictor discharge to skeletal muscle reflexively in response
      to orthostatic stimuli.

PMID- 11222118
TI  - Selective enhancement of sensitivity to endothelin-1 despite normal endothelium
      dependent relaxation in subcutaneous resistance arteries isolated from patients
      with Type I diabetes.
AB  - Type I diabetes mellitus is associated with abnormal vascular function, but few
      studies have documented its effects on human resistance arteries. This study
      aimed to determine whether endothelial cell and smooth muscle cell function was
      impaired in resistance arteries isolated from patients with this condition.
      Biopsies of subcutaneous gluteal fat were taken from 12 patients with Type I
      diabetes (age 32.3+/-1.9 years; duration of diabetes 13.9+/-2.5 years) and 12
      matched controls (age 31.5+/-2.2 years). Levels of glycosylated haemoglobin were
      higher (P<0.0001) in patients (9.38+/-0.35%) than in controls (5.48+/-0.11%), but
      most (11 out of 12) patients showed no evidence of microvascular disease. Small
      resistance arteries were isolated from the biopsies, and isometric responses to
      vasoconstrictors and vasodilators were measured in a small-vessel myograph. The
      magnitude and sensitivity of responses to noradrenaline and potassium were not
      different in diabetic patients compared with controls. In contrast, the
      sensitivity (pD(2); negative logarithm of the concentration of the
      vasoconstrictor required to produce 50% of the maximum effect), but not the
      magnitude, of contraction in response to endothelin-1 in vessels from patients
      (8.87+/-0.12) was significantly (P=0.02) greater than in those from controls
      (8.40+/-0.13). Endothelium-dependent (acetylcholine, bradykinin, A23187) and 
      independent (3'-morpholinosydnonimine) relaxation responses were unaltered in
      patients with Type I diabetes. These results suggest a selective alteration in
      receptor activity in the endothelium, and contrast strikingly with the
      considerable evidence of impaired endothelium-dependent relaxation in Type I
      diabetes. The present study indicates, therefore, that endothelial cell function
      is largely maintained in resistance arteries from patients with well controlled
      Type I diabetes. The increased response to endothelin-1 supports the possibility
      that more significant abnormalities would be evident in patients with severe
      microvascular complications.

PMID- 11222119
TI  - Effects of nitric oxide synthase inhibition on angiotensin receptors and
      metabolism in the pregnant hypertensive rat.
AB  - Endothelial dysfunction and a consequent decrease in nitric oxide production have
      been implicated in the pathogenesis of pre-eclampsia. A prominent feature of the
      pre-eclamptic syndrome is a loss of the pregnancy-induced refractoriness to
      infused pressor agents, such as angiotensin. In this study, we sought to
      determine whether a decrease in nitric oxide production might be linked via
      changes in angiotensin II receptors and angiotensin II metabolism to changes in
      pressor sensitivity to infused angiotensin II. Pregnant and non-pregnant
      spontaneously hypertensive rats (SHRs) were randomly allocated to receive 5 mg x
      kg(-1) x day(-1) N(G)-nitro-L-arginine methyl ester (L-NAME) in the drinking
      water or drinking water alone from days 7 to 14 of gestation. Steady-state
      metabolic clearance studies of angiotensin II were then performed, or tissues
      were harvested for angiotensin II receptor studies. Treatment with L-NAME caused
      an increase in systolic pressure (P<0.001) in both pregnant and non-pregnant
      rats, while urinary protein excretion increased only in the pregnant SHRs
      (P<0.001). Plasma angiotensin II levels were significantly increased in the L
      NAME-treated SHRs compared with controls (non-pregnant, P<0.0005; pregnant,
      P<0.01). The metabolic clearance rate of angiotensin II was decreased by L-NAME
      treatment in non-pregnant SHRs (P<0.05), but was increased by L-NAME treatment in
      the pregnant rats (P<0.01). In the aorta, the angiotensin II receptor number
      increased after treatment with L-NAME in both non-pregnant (P<0.0005) and
      pregnant (P<0.05) SHRs, and the dissociation constant increased in the non
      pregnant SHRs (P<0.005). Thus treatment of SHRs with L-NAME increased blood
      pressure, as well as the circulating angiotensin II concentration and vascular
      angiotensin II receptor expression. However, treatment with L-NAME did not affect
      pressor sensitivity to infused angiotensin II. We conclude, therefore, that
      although a decrease in nitric oxide production is associated with changes in
      angiotensin II concentrations and receptor numbers, it does not induce changes in
      pressor sensitivity to infused angiotensin II in the SHR.

PMID- 11222120
TI  - Comparison of nasal pH values in black and white individuals with normal and high
      blood pressure.
AB  - Salt-sensitive hypertension is common in people of African origin, and may be
      caused by increased transepithelial sodium absorption. The pH of nasal secretions
      is negatively correlated with the difference in Na(+) concentration between nasal
      secretions and plasma, and may be a marker of transepithelial sodium absorption.
      Nasal pH was measured using a probe sited under the inferior turbinate.
      Measurements of nasal pH were reproducible, with a coefficient of variation of
      3.3% for repeated measurements on the same day and of 2.7% between measurements
      on different days. Nasal pH did not correlate with nasal potential difference, a
      measure of transepithelial sodium absorption. Nasal pH was significantly lower in
      89 black individuals (24 normotensive and 65 hypertensive) than in 51 white
      individuals (26 normotensive and 25 hypertensive) (black normotensive. 6.44+/
      0.08; black hypertensive, 6.62+/-0.05; white normotensive, 6.91+/-0.06; white
      hypertensive, 6.98+/-0.06), after adjustment for age, gender, current smoking
      status, body mass index and 24 h urinary sodium excretion (P=0.002), but was not
      significantly different between the normotensive and hypertensive individuals.
      Nasal pH was more acidic in black than in white individuals, which may represent
      generalized up-regulation of sodium transport in black people. However, the lack
      of correlation between nasal pH and potential difference suggests that nasal pH
      is, at best, only weakly related to transepithelial sodium absorption. Ethnic
      differences in nasal pH may be of direct relevance in the airways, as many of the
      functions of airway surface liquid are dependent on pH.

PMID- 11222121
TI  - Water ingestion increases sympathetic vasoconstrictor discharge in normal human
      subjects.
AB  - A marked pressor response to water drinking has been observed in patients with
      autonomic failure and in the elderly, and has been attributed to sympathetic
      vasoconstrictor activation, despite the absence of such a pressor response in
      healthy subjects with intact sympathetic mechanisms. We investigated whether
      water drinking in normal subjects affected peripheral sympathetic neural
      discharge and its effect on vascular resistance. In nine normal human subjects,
      we examined the effect of water ingestion on muscle sympathetic neural activity
      from the peroneal nerve, as multi-unit bursts (muscle sympathetic nerve activity;
      MSNA) and as single-unit impulses (s-MSNA) with vasoconstrictor function, and on
      calf vascular resistance for 120 min. In each subject, water ingestion caused
      increases in s-MSNA and MSNA which peaked at 30 min after ingestion; they
      increased respectively (mean+/-S.E.M.) from 42+/-4 to 58+/-5 impulses/100 beats
      (P<0.01) and from 36+/-4 to 51+/-5 bursts/100 beats (P<0.001). There were
      corresponding increases in calf vascular resistance and in plasma noradrenaline
      levels. A significant correlation occurred between all of these data. In
      conclusion, measurement of MSNA has provided direct evidence that water drinking
      in normal human subjects increases sympathetic nerve traffic, leading to
      peripheral vasoconstriction. This sympathetic activation was not accompanied by
      significant changes in arterial blood pressure.

PMID- 11222122
TI  - Increased levels of high-density lipoprotein cholesterol are ineffective in
      inhibiting the development of immune responses to oxidized low-density
      lipoprotein and atherosclerosis in transgenic rabbits expressing human
      apolipoprotein (apo) A-I with severe hypercholesterolaemia.
AB  - High levels of high-density lipoprotein (HDL) cholesterol have been reported to
      protect against the development of atherosclerosis in humans by increasing
      reverse cholesterol transport and inhibiting the oxidation of low-density
      lipoprotein (LDL) due to the paraoxonase content of HDL. The purpose of the
      present study was to assess if there are any relationships between in vivo
      increases in serum levels of immunological LDL oxidation markers [autoantibodies
      against oxidized LDL, autoantibodies against malondialdehyde-modified LDL, LDL
      immune complexes and anti-cardiolipin autoantibodies], paraoxonase activity and
      the development of atherosclerosis in control rabbits and in transgenic rabbits
      expressing human apolipoprotein (apo) A-I. A total of 13 apo A-I transgenic
      rabbits and 18 non-transgenic littermates were fed on a cholesterol-rich diet
      (0.4%, w/w) for 14 weeks, and were monitored at weeks 0, 2, 6, 10 and 14. Aortic
      atherosclerotic lesions were measured at the end of this period. Human apo A-I
      transgenic rabbits with high HDL cholesterol levels were not protected against
      the development of atherosclerosis when they were fed on a cholesterol-rich diet
      which induced dramatic hypercholesterolaemia. Immunological markers of LDL
      oxidation increased and serum paraoxonase activity decreased similarly in control
      and transgenic rabbits. In conclusion, the present study demonstrates that high
      HDL cholesterol levels are ineffective in inhibiting increases in immunological
      markers of LDL oxidation and the development of atherosclerosis in a mammal with
      severe hypercholesterolaemia.

PMID- 11222123
TI  - A shot in the dark: the silent quest of a free-flying phonotactic fly.
AB  - To reproduce, females of the parasitoid fly Ormia ochracea detect and localise a
      calling male cricket upon which they deposit their endoparasitic larvae. Calling
      male crickets are therefore subject to both sexual and natural selection by
      simultaneously attracting mates and phonotactic parasitoids. The possible
      strategy of song interruption employed by the cricket host to reduce his
      attractiveness to acoustic parasitoids was tested in the laboratory by examining
      the fly's phonotactic quest in response to synthetic cricket songs. Phonotactic
      flight trajectories were recorded in three dimensions with a stereo infrared
      video tracking system while the sound stimulus was controlled on-line as a
      function of the fly's position in space. Within a single flight, three distinct
      phases could be observed: a take-off phase, a cruising phase, during which course
      and altitude were rather constant, and a landing phase characterised by a
      spiralling descent towards the sound source. The flies showed remarkable
      phonotactic accuracy in darkness; they landed at a mean distance of 8.2 cm from
      the centre of the loudspeaker after a flight distance of approximately 4 m. The
      present data illustrate the fly's surprising ability to gauge the direction and
      distance of a sound source in three dimensions and, subsequently, to find it in
      darkness and silence.

PMID- 11222124
TI  - Properties of the mammalian and yeast metal-ion transporters DCT1 and Smf1p
      expressed in Xenopus laevis oocytes.
AB  - Transition metals are essential for many metabolic processes, and their
      homeostasis is crucial for life. Metal-ion transporters play a major role in
      maintaining the correct concentrations of the various metal ions in living cells.
      Little is known about the transport mechanism of metal ions by eukaryotic cells.
      Some insight has been gained from studies of the mammalian transporter DCT1 and
      the yeast transporter Smf1p by following the uptake of various metal ions and
      from electrophysiological experiments using Xenopus laevis oocytes injected with
      RNA copies (c-RNA) of the genes for these transporters. Both transporters
      catalyze the proton-dependent uptake of divalent cations accompanied by a
      'slippage' phenomenon of different monovalent cations unique to each transporter.
      Here, we further characterize the transport activity of DCT1 and Smf1p, their
      substrate specificity and their transport properties. We observed that Zn(2+) is
      not transported through the membrane of Xenopus laevis oocytes by either
      transporter, even though it inhibits the transport of the other metal ions and
      enables protons to 'slip' through the DCT1 transporter. A special construct
      (Smf1p-s) was made to enhance Smf1p activity in oocytes to enable
      electrophysiological studies of Smf1p-s-expressing cells. 54Mn(2+) uptake by
      Smf1p-s was measured at various holding potentials. In the absence of Na(+) and
      at pH 5.5, metal-ion uptake was not affected by changes in negative holding
      potentials. Elevating the pH of the medium to 6.5 caused metal-ion uptake to be
      influenced by the holding potential: ion uptake increased when the potential was
      lowered. Na(+) inhibited metal-ion uptake in accordance with the elevation of the
      holding potential. A novel clutch mechanism of ion slippage that operates via
      continuously variable stoichiometry between the driving-force pathway (H(+)) and
      the transport pathway (divalent metal ions) is proposed. The possible
      physiological advantages of proton slippage through DCT1 and of Na(+) slippage
      through Smf1p are discussed.

PMID- 11222125
TI  - ATP-regenerating system in the cilia of Paramecium caudatum.
AB  - The energy supply for eukaryotic ciliary and flagellar movement is thought to be
      maintained by ATP-regenerating enzymes such as adenylate kinase, creatine kinase
      and arginine kinase. In this study, the energy-supplying system for the ciliary
      movement of Paramecium caudatum was examined. Arginine kinase and adenylate
      kinase activities were detected in the cilia. To demonstrate that phosphoarginine
      satisfactorily supplies high-energy phosphate compounds into the narrow ciliary
      space, we prepared an intact ciliated cortical sheet from live Paramecium
      caudatum. These cortical sheets, with an intact ciliary membrane, produced a half
      closed system in which each cilium was covered with a ciliary membrane with an
      opening to the cell body. Ciliary beating on the intact cortical sheets was
      induced by perfusing not only ATP but also ADP. Addition of phosphoarginine (0.2
      mmol l(-1)) increased the beat frequency. A further increase in beat frequency
      was observed in 0.4 mmol l(-1) phosphoarginine, and this was enhanced when the
      cilia were reactivated with relatively low concentrations of ATP. We have
      demonstrated that phosphoarginine supplies energy as a 'phosphagen' for ciliary
      beating in Paramecium caudatum, suggesting that phosphoarginine functions not
      only as a reservoir of energy but also as a transporter of energy in these
      continuously energy-consuming circumstances.
      http://www.biologists.com/JEB/movies/jeb3123.html

PMID- 11222126
TI  - Daily variations in crustacean hyperglycaemic hormone and serotonin
      immunoreactivity during the development of crayfish.
AB  - The present study investigated changes in crustacean hyperglycaemic hormone (CHH)
      and serotonin (5-hydroxytryptamine, 5-HT) immunoreactivity in the retina and the
      X-organ/sinus gland complex (XO-SG) of the crayfish Procambarus clarkii at two
      developmental stages, post-embryonic stage two (PO2) and the juvenile stage, at
      three different times of day, under a photoperiod cycle of 12 h:12 h L:D, using
      qualitative and quantitative immunohistochemical methods. In the retina, CHH
      immunoreactivity is located in the tapetal cells, while 5-HT immunoreactivity is
      found in the retinular cells. In the XO-SG, CHH-immunoreactivity is localized to
      the CHH-producing cell perikarya and in their axons and endings in the sinus
      gland, while 5-HT immunoreactivity is restricted to axon endings branching into
      the perikarya of the CHH-producing cells. A stereological analysis demonstrates
      that the PO2 and juvenile stages show significant differences in the amount of
      the immunoreactive CHH and 5-HT material at the three selected time points,
      indicating daily and related changes in the levels of CHH and 5-HT in the XO-SG
      and the retina. Our findings therefore support the idea that daily rhythms in the
      secretory activity of the XO-SG complex affect the circadian sensitivity of the
      eye. Furthermore, the differences found between the PO2 and juvenile stages
      suggest that both CHH and 5-HT are key factors in the development of the
      circadian rhythm of retinal sensitivity.

PMID- 11222127
TI  - Oxygen uptake by embryos and ovigerous females of two intertidal crabs,
      Heterozius rotundifrons (Belliidae) and Cyclograpsus lavauxi (Grapsidae): scaling
      and the metabolic costs of reproduction.
AB  - Heterozius rotundifrons and Cyclograpsus lavauxi are crabs of similar size, whose
      intertidal habitats overlap. They differ in the number and size of their eggs. A
      2 g ovigerous H. rotundifrons incubates 675 large yolky eggs (mean single-egg
      mass 269 microg; egg clutch 9.15 % of mass of female crab; increasing to 435
      microg and 13.4 % at hatching). The egg clutch of a 2 g C. lavauxi is larger
      (15.4 % of crab mass increasing to 18.9 % at hatching) and contains more numerous
      (28 000), smaller (10.9 microg increasing to 20.3 microg) eggs. The longer
      development time of the larger eggs (194 days versus 56 days at 15 degrees C)
      results from a delayed increase in metabolic rate (diapause) and not metabolic
      scaling. On the basis of the total mass of single eggs, the mass-specific
      metabolic rates of early embryonic stages of H. rotundifrons (0.72 micromol g(-1
      )h(-1) for the blastula stage at 15 degrees C) and C. lavauxi (1.13 micromol g(-1
      )h(-1)) were similar to those of the adult female crabs (0.70 micromol g(-1 )h(
      1) for H. rotundifrons and 0.91 micromol g(-1 )h(-1) for C. lavauxi) and
      increased 13- and 10-fold, respectively, by the time of hatching. Thus, early
      embryonic metabolic rates were much lower than expected from their mass, but the
      metabolic rates of pre-hatching embryos were consistent with the allometry of
      juveniles and adults. Possible interpretations of this apparently anomalous
      scaling of embryonic metabolic rates are discussed. Mass-specific rates of oxygen
      consumption by ovigerous females (including the eggs) of both species were higher
      than for non-ovigerous crabs, in water and in air, and increased greatly during
      the development of the eggs. This difference was attributable mainly to the
      increasing metabolic rates of the attached embryos, but early ovigerous crabs
      (blastula stage) of both species also demonstrated a small elevation in metabolic
      rate by the crab itself, i.e. a metabolic cost of egg-bearing. In contrast, the
      elevation of the rate of oxygen consumption by late ovigerous females of C.
      lavauxi was less than predicted from the metabolic rate of eggs in a stirred
      respirometer. This suggests that, towards the end of development in C. lavauxi,
      the oxygen supply to the eggs in situ may be diffusion-limited by unstirred
      layers, an effect not observed for the larger eggs and more open egg clutch of H.
      rotundifrons. The cost of development, in terms of total oxygen consumption of
      single eggs, from extrusion to hatching, was 3.34 micromol O2 (approximately 1.5
      J) for H. rotundifrons and 0.105 micromol O2 (approximately 0.05 J) for C.
      lavauxi. This 30-fold ratio approximates the ratios of their initial masses and
      yolk contents but represents only approximately one-third of the initial energy
      contents of the eggs.

PMID- 11222128
TI  - Mechanics of limb bone loading during terrestrial locomotion in the green iguana
      (Iguana iguana) and American alligator (Alligator mississippiensis).
AB  - In vivo measurements of strain in the femur and tibia of Iguana iguana (Linnaeus)
      and Alligator mississippiensis (Daudin) have indicated three ways in which limb
      bone loading in these species differs from patterns observed in most birds and
      mammals: (i) the limb bones of I. iguana and A. mississippiensis experience
      substantial torsion, (ii) the limb bones of I. iguana and A. mississippiensis
      have higher safety factors than those of birds or mammals, and (iii) load
      magnitudes in the limb bones of A. mississippiensis do not decrease uniformly
      with the use of a more upright posture. To verify these patterns, and to evaluate
      the ground and muscle forces that produce them, we collected three-dimensional
      kinematic and ground reaction force data from subadult I. iguana and A.
      mississippiensis using a force platform and high-speed video. The results of
      these force/kinematic studies generally confirm the loading regimes inferred from
      in vivo strain measurements. The ground reaction force applies a torsional moment
      to the femur and tibia in both species; for the femur, this moment augments the
      moment applied by the caudofemoralis muscle, suggesting large torsional stresses.
      In most cases, safety factors in bending calculated from force/video data are
      lower than those determined from strain data, but are as high or higher than the
      safety factors of bird and mammal limb bones in bending. Finally, correlations
      between limb posture and calculated stress magnitudes in the femur of I. iguana
      confirm patterns observed during direct bone strain recordings from A.
      mississippiensis: in more upright steps, tensile stresses on the anterior cortex
      decrease, but peak compressive stresses on the dorsal cortex increase.
      Equilibrium analyses indicate that bone stress increases as posture becomes more
      upright in saurians because the ankle and knee extensor muscles exert greater
      forces during upright locomotion. If this pattern of increased bone stress with
      the use of a more upright posture is typical of taxa using non-parasagittal
      kinematics, then similar increases in load magnitudes were probably experienced
      by lineages that underwent evolutionary shifts to a non-sprawling posture. High
      limb bone safety factors and small body size in these lineages could have helped
      to accommodate such increases in limb bone stress.

PMID- 11222129
TI  - Reproductive behaviour in the male cricket Gryllus bimaculatus DeGeer. I.
      Structure and function of the genitalia.
AB  - We have investigated the morphology and physiology of the genitalia of the male
      cricket to establish a basis for neuroethological study of its reproductive
      behaviour. First, the structure of the phallic complex, including the dorsal
      pouch, guiding rod, epiphallus, ventral lobes and median pouch, are described, as
      are the muscles, cuticle, membranes and biomechanics of copulation. The
      innervation and sensory receptors have also been examined. Second, the functional
      role of the muscle in each genital organ has been determined by direct
      observation of muscle contraction during spontaneous or evoked movements and by
      analysis of the changes in movements after the ablation of the muscle. Third, for
      the flexible membranous organs, the ventral lobes and median pouch, the passages
      for haemolymph and their dynamic properties have been examined using petroleum
      jelly. Fourth, the sequence of coordinated motor actions performed by the
      internal and external genital organs, which were induced in both restrained and
      dissected males using newly developed techniques, has been analyzed during
      tethered copulation and spermatophore formation. As a result, the mechanisms of
      copulation and spermatophore formation are now more fully understood.

PMID- 11222130
TI  - Reproductive behaviour in the male cricket Gryllus bimaculatus DeGeer. II. Neural
      control of the genitalia.
AB  - To understand the neural mechanisms of reproductive behaviour in the male
      cricket, we identified motor neurones innervating the muscles in each genital
      organ by backfilling with cobalt/nickel and recording their extracellular spike
      activity from nerve bundles of the terminal abdominal ganglion during tethered
      copulation and spermatophore formation. During tethered copulation, at least two
      motor neurones innervating two ipsilateral muscles were activated during
      projection of the guiding rod of the phallic dorsal pouch. Only one motor
      neurone, innervating four ipsilateral muscles of the dorsal pouch, was
      responsible for spermatophore extrusion by deforming the dorsal pouch. For
      spermatophore transfer, three motor neurones, singly innervating three epiphallus
      muscles, played a major role in opening passages for haemolymph to enter the
      ventral lobes and median pouch by bending the epiphallus. Two ventral lobe and 3
      5 median pouch motor neurones seemed to play a role in expanding or folding the
      two membranous structures by relaxing or contracting their muscle fibres. After
      spermatophore transfer, most of the genital motor neurones exhibited a rhythmic
      burst of action potentials causing movement of the phallic complex coupled with
      strong abdominal contractions. For spermatophore formation, the genital motor
      neurones began to accelerate their rhythmic bursts approximately 30 s prior to
      subgenital plate opening and then changed their activity to tonic bursting or
      silence. The results have allowed us to describe the timing of the onset and
      termination of genital muscle contraction more precisely than before, to examine
      the neural mechanisms of copulatory motor control and to speculate on the neural
      organization of the reproductive centre for spermatophore extrusion and
      protrusion.

PMID- 11222131
TI  - Gliding flight in a jackdaw: a wind tunnel study.
AB  - We examined the gliding flight performance of a jackdaw Corvus monedula in a wind
      tunnel. The jackdaw was able to glide steadily at speeds between 6 and 11 m s(
      1). The bird changed its wingspan and wing area over this speed range, and we
      measured the so-called glide super-polar, which is the envelope of fixed-wing
      glide polars over a range of forward speeds and sinking speeds. The glide super
      polar was an inverted U-shape with a minimum sinking speed (V(ms)) at 7.4 m s(-1)
      and a speed for best glide (V(bg)) at 8.3 m s(-)). At the minimum sinking speed,
      the associated vertical sinking speed was 0.62 m s(-1). The relationship between
      the ratio of lift to drag (L:D) and airspeed showed an inverted U-shape with a
      maximum of 12.6 at 8.5 m s(-1). Wingspan decreased linearly with speed over the
      whole speed range investigated. The tail was spread extensively at low and
      moderate speeds; at speeds between 6 and 9 m s(-1), the tail area decreased
      linearly with speed, and at speeds above 9 m s(-1) the tail was fully furled.
      Reynolds number calculated with the mean chord as the reference length ranged
      from 38 000 to 76 000 over the speed range 6-11 m s(-1). Comparisons of the
      jackdaw flight performance were made with existing theory of gliding flight. We
      also re-analysed data on span ratios with respect to speed in two other bird
      species previously studied in wind tunnels. These data indicate that an equation
      for calculating the span ratio, which minimises the sum of induced and profile
      drag, does not predict the actual span ratios observed in these birds. We derive
      an alternative equation on the basis of the observed span ratios for calculating
      wingspan and wing area with respect to forward speed in gliding birds from
      information about body mass, maximum wingspan, maximum wing area and maximum
      coefficient of lift. These alternative equations can be used in combination with
      any model of gliding flight where wing area and wingspan are considered to
      calculate sinking rate with respect to forward speed.

PMID- 11222132
TI  - Field estimates of body drag coefficient on the basis of dives in passerine
      birds.
AB  - During forward flight, a bird's body generates drag that tends to decelerate its
      speed. By flapping its wings, or by converting potential energy into work if
      gliding, the bird produces both lift and thrust to balance the pull of gravity
      and drag. In flight mechanics, a dimensionless number, the body drag coefficient
      (C(D,par)), describes the magnitude of the drag caused by the body. The drag
      coefficient depends on the shape (or streamlining), the surface texture of the
      body and the Reynolds number. It is an important variable when using flight
      mechanical models to estimate the potential migratory flight range and
      characteristic flight speeds of birds. Previous wind tunnel measurements on dead,
      frozen bird bodies indicated that C(D,par) is 0.4 for small birds, while large
      birds should have lower values of approximately 0.2. More recent studies of a few
      birds flying in a wind tunnel suggested that previous values probably
      overestimated C(D,par). We measured maximum dive speeds of passerine birds during
      the spring migration across the western Mediterranean. When the birds reach their
      top speed, the pull of gravity should balance the drag of the body (and wings),
      giving us an opportunity to estimate C(D,par). Our results indicate that C(D,par)
      decreases with increasing Reynolds number within the range 0.17-0.77, with a mean
      C(D,par) of 0.37 for small passerines. A somewhat lower mean value could not be
      excluded because diving birds may control their speed below the theoretical
      maximum. Our measurements therefore support the notion that 0.4 (the 'old'
      default value) is a realistic value of C(D,par) for small passerines.

PMID- 11222133
TI  - Maximum cold-induced food consumption in mice selected for high locomotor
      activity: implications for the evolution of endotherm energy budgets.
AB  - We studied house mice (Mus domesticus) that had been artificially selected for
      high activity to test the hypothesis that a high capacity for energy assimilation
      in cold-exposed endotherms could evolve as a correlated response to selection for
      increased locomotor activity. After 10 generations of selection for increased
      voluntary wheel-running, mice from four selected lines ran 75 % more wheel
      revolutions per day than did mice from four random-bred, control lines. The
      maximum cold-induced rates of food consumption (C(max); mean 10.6 g day(-1)) and
      energy assimilation (A(max); mean 141 kJ day(-1)) were not significantly higher
      in the selected than in the control mice. However, in cold-exposure trials, mice
      from the selected lines maintained body mass better than did mice from the
      control lines. C(max) and A(max) were positively correlated with the amount of
      wheel-running activity measured before cold-exposure and also with the rates of
      food consumption measured when the mice had access to running wheels. In females
      at least, the correlation was significant not only among individuals but also
      among adjusted means of the replicate lines, which suggests the presence of a
      positive genetic correlation between the traits. Thus, despite the lack of a
      significant difference between the selected and control lines in maximum rate of
      food consumption, the remaining results conform to the hypothesis that a
      selection for increased locomotor activity could be a factor behind the evolution
      of the ability to sustain activity and maintain energy balance during prolonged
      cold-exposure, as occurred during the evolution of mammalian and avian
      endothermy.

PMID- 11222134
TI  - Regional effects of voluntary exercise on cell size and contraction-frequency
      responses in rat cardiac myocytes.
AB  - A model of voluntary exercise, in which rats are given free access to a running
      wheel over a 14-week period, led to left ventricular hypertrophy. To test whether
      the hypertrophic response to exercise was uniformly distributed across the
      ventricular wall, single ventricular myocytes were isolated from the sub
      epicardium (EPI) and sub-endocardium (ENDO) of exercised rats and from sedentary
      rats for comparison. Cellular hypertrophy (approximately 20 % greater cell
      volume) was seen in ENDO cells from exercised animals, but no significant changes
      were observed in EPI cells when compared with sedentary controls. This regional
      effect of exercise may be a response to transmural changes in ventricular wall
      stress and/or strain. Cell contraction was measured as cell shortening in ENDO
      and EPI cells at stimulation frequencies between 1 and 9 Hz at 37 degrees C.
      Exercise training had no effect on cell shortening. Positive and negative
      contraction-frequency relationships (CFRs) were found in both EPI and ENDO cells
      between 1 and 5 Hz; at higher frequencies (5-9 Hz), all myocytes displayed a
      negative CFR. The CFR of a myocyte was, therefore, independent of regional origin
      and unaffected by exercise. These results suggest that, in vivo, the rat heart
      displays a negative CFR. We conclude that increased cell size may be a more
      important adaptive response to exercise than a modification of excitation
      contraction coupling.

PMID- 11222135
TI  - Effects of season on kidney morphology in house sparrows.
AB  - Seasonal variability in kidney morphology of the house sparrow Passer domesticus
      was examined using light microscopy. Sparrows were captured from the wild in
      winter, spring, summer and autumn. The kidneys were perfused with half-strength
      Karnovsky's fixative and processed for light microscopy by embedding in either
      paraffin wax or JB4 acrylic resin. Absolute volumes of the kidneys, their
      components (cortex, medulla and blood vessels), components of the nephron (renal
      corpuscles, proximal tubules, loops of Henle, distal tubules and collecting
      ducts) and the capillaries surrounding the nephron were quantified using
      stereology. Tissue processed in paraffin wax had a mean shrinkage of 17.7 %
      compared with 10.1 % in JB4 resin. Absolute volumes of the kidneys and nephrons
      were compared statistically between tissue processing methods and among seasons.
      Absolute volumes of the structures within the kidneys were not significantly
      different between treatments or among seasons. Within the nephron, the only
      measured variables to show significant differences were the absolute volumes of
      the distal tubules and cortical collecting ducts between tissue processing
      treatments. Thus, kidney morphology was relatively unaffected by changes in
      season. In addition, the results show that embedding tissue using acrylic resin
      causes less shrinkage, and it should therefore be the preferred embedding medium
      for quantitative morphologists.

PMID- 11222136
TI  - Strike feeding behavior in the muskellunge, Esox masquinongy: contributions of
      the lateral line and visual sensory systems.
AB  - The muskellunge, Esox masquinongy, is a predatory esocid fish with well-developed
      visual and lateral line systems. The purpose of this study was to determine the
      relative roles of these two sensory modalities in organizing the strike behavior
      of the animal. Subadult muskellunge were videotaped in a test arena while feeding
      on fathead minnows (Pimephales promelas). Animals were tested under five
      conditions: (i) control animals in which the visual and lateral line systems were
      intact; (ii) animals with lateral line afference suppressed by immersion for 12
      24 h in 0.1 mmol l(-1) CoCl2; (iii) animals blinded by bilateral optic nerve
      transection; (iv) animals that had been unilaterally blinded; and (v) animals in
      which the lateral line system had been unilaterally denervated. The feeding
      behavior of the muskellunge consists of two phases: a slow stalk of the prey with
      minimal body movement followed by an explosive C- or S-start lunge at the prey.
      Quantitative comparisons of animals in the five test groups indicate that,
      although vision is used in the initial acquisition of the prey, both vision and
      the lateral line system play important roles in determining the initiation of the
      rapid strike. The lateral line system may play a critical role in the final
      capture of the prey at the end of the strike. In addition, lateral-line
      suppressed muskellunge strongly alter their approaches to more distant prey.
      Bilaterally blinded muskellunge do not stalk their prey, but will lunge only at
      prey that are at close range. Unilaterally blinded or denervated muskellunge also
      alter their detection of and approach to prey, attending to a wider region of the
      intact sensory hemisphere. Our data suggest not only that the visual and lateral
      line systems play complementary roles in the feeding behavior sequence but also
      that each system plays a more or less dominant role during consecutive phases of
      the behavior.

PMID- 11222137
TI  - A new visualization approach for identifying mutations that affect
      differentiation and organization of the Drosophila ommatidia.
AB  - The Drosophila eye is widely used as a model system to study neuronal
      differentiation, survival and axon projection. Photoreceptor differentiation
      starts with the specification of a founder cell R8, which sequentially recruits
      other photoreceptor neurons to the ommatidium. The eight photoreceptors that
      compose each ommatidium exist in two chiral forms organized along two axes of
      symmetry and this pattern represents a paradigm to study tissue polarity. We have
      developed a method of fluoroscopy to visualize the different types of
      photoreceptors and the organization of the ommatidia in living animals. This
      allowed us to perform an F(1) genetic screen to isolate mutants affecting
      photoreceptor differentiation, survival or planar polarity. We illustrate the
      power of this detection system using known genetic backgrounds and new mutations
      that affect ommatidial differentiation, morphology or chirality.

PMID- 11222138
TI  - Tissue-restricted expression of thrombomodulin in the placenta rescues
      thrombomodulin-deficient mice from early lethality and reveals a secondary
      developmental block.
AB  - The endothelial cell surface receptor thrombomodulin (TM) inhibits blood
      coagulation by forming a complex with thrombin, which then converts protein C
      into the natural anticoagulant, activated protein C. In mice, a loss of TM
      function causes embryonic lethality at day 8.5 p.c. (post coitum) before
      establishment of a functional cardiovascular system. At this developmental stage,
      TM is expressed in the developing vasculature of the embryo proper, as well as in
      non-endothelial cells of the early placenta, giant trophoblast and parietal
      endoderm. Here, we show that reconstitution of TM expression in extraembryonic
      tissue by aggregation of tetraploid wild-type embryos with TM-null embryonic stem
      cells rescues TM-null embryos from early lethality. TM-null tetraploid embryos
      develop normally during midgestation, but encounter a secondary developmental
      block between days 12.5 and 16.5 p.c. Embryos lacking TM develop lethal
      consumptive coagulopathy during this period, and no live embryos are retrieved at
      term. Morphogenesis of embryonic blood vessels and other organs appears normal
      before E15. These findings demonstrate a dual role of TM in development, and that
      a loss of TM function disrupts mouse embryogenesis at two different stages. These
      two functions of TM are exerted in two distinct tissues: expression of TM in non
      endothelial extraembryonic tissues is required for proper function of the early
      placenta, while the absence of TM from embryonic blood vessel endothelium causes
      lethal consumptive coagulopathy.

PMID- 11222139
TI  - Specification of embryonic axes begins before cleavage in normal mouse
      development.
AB  - Studies on the development of aggregated, isolated and rearranged blastomeres
      have engendered the view that in mammals, unlike most other animals, egg
      organization has no role in the genesis of asymmetries that are essential for
      cellular diversification and the specification of embryonic axes. Such
      asymmetries are assumed to arise post-zygotically through interactions between
      initially naive cells. However, various findings are difficult to reconcile with
      this view. Here, a consistent relationship between the structure of the
      blastocyst and the two-cell stage in the mouse has been found using a strictly
      non-invasive marking technique: injection of small oil drops into the substance
      of the zona pellicuda. This has revealed that both the embryonic-abembryonic axis
      of the blastocyst and its plane of bilateral symmetry are normally orthogonal to
      the plane of first cleavage. This relationship was also seen when denuded two
      cell conceptuses were prevented from rotating during subsequent cleavage by
      immobilizing them in a gel. Therefore, during normal mouse development the axes
      of the blastocyst, which have been implicated in establishing those of the fetus,
      are already specified by the onset of cleavage.

PMID- 11222140
TI  - The type I serine/threonine kinase receptor Alk8/Lost-a-fin is required for
      Bmp2b/7 signal transduction during dorsoventral patterning of the zebrafish
      embryo.
AB  - Ventral specification of mesoderm and ectoderm depends on signaling by members of
      the bone morphogenetic protein (Bmp) family. Bmp signals are transmitted by a
      complex of type I and type II serine/threonine kinase transmembrane receptors.
      Here, we show that Alk8, a novel member of the Alk1 subgroup of type I receptors,
      is disrupted in zebrafish lost-a-fin (laf) mutants. Two alk8/laf null alleles are
      described. In laf(tm110), a conserved extracellular cysteine residue is replaced
      by an arginine, while in laf(m100), Alk8 is prematurely terminated directly after
      the transmembrane domain. The zygotic effect of both mutations leads to
      dorsalization of intermediate strength. A much stronger dorsalization, similar to
      that of bmp2b/swirl and bmp7/snailhouse mutants, however, is obtained by
      inhibiting both maternally and zygotically supplied alk8 gene products with
      morpholino antisense oligonucleotides. The phenotype of laf mutants and alk8
      morphants can be rescued by injected mRNA encoding Alk8 or the Bmp-regulated
      transcription factor Smad5, but not by mRNA encoding Bmp2b or Bmp7. Conversely,
      injected mRNA encoding a constitutively active version of Alk8 can rescue the
      strong dorsalization of bmp2b/swirl and bmp7/snailhouse mutants, whereas
      smad5/somitabun mutant embryos do not respond. Altogether, the data suggest that
      Alk8 acts as a Bmp2b/7 receptor upstream of Smad5.

PMID- 11222141
TI  - Lost-a-fin encodes a type I BMP receptor, Alk8, acting maternally and zygotically
      in dorsoventral pattern formation.
AB  - TGFbeta signaling pathways of the bone morphogenetic protein (BMP) subclass are
      essential for dorsoventral pattern formation of both vertebrate and invertebrate
      embryos. Here we determine by chromosomal mapping, linkage analysis, cDNA
      sequencing and mRNA rescue that the dorsalized zebrafish mutant lost-a-fin (laf)
      is defective in the gene activin receptor-like kinase 8 (alk8), which encodes a
      novel type I TGFbeta receptor. The alk8 mRNA is expressed both maternally and
      zygotically. Embyros that lack zygotic, but retain maternal Laf/Alk8 activity,
      display a weak dorsalization restricted to the tail and die by 3 days
      postfertilization. We rescued the laf dorsalized mutant phenotype by alk8 mRNA
      injection and generated homozygous laf/alk8 mothers to investigate the maternal
      role of Laf/Alk8 activity. Adult fish lacking Laf/Alk8 activity are fertile,
      exhibit a growth defect and are significantly smaller than their siblings.
      Embryos derived from homozygous females, which lack both maternal and zygotic
      Laf/Alk8 activity, display a strongly dorsalized mutant phenotype, no longer
      limited to the tail. These mutant embryos lack almost all gastrula ventral cell
      fates, with a concomitant expansion of dorsal cell types. During later stages,
      most of the somitic mesoderm and neural tissue circumscribe the dorsoventral axis
      of the embryo. Zygotic laf/alk8 mutants can be rescued by overexpression of the
      BMP signal transducer Smad5, but not the Bmp2b or Bmp7 ligands, consistent with
      the Laf/Alk8 receptor acting within a BMP signaling pathway, downstream of a
      Bmp2b/Bmp7 signal. Antibodies specific for the phosphorylated, activated form of
      Smad1/5, show that BMP signaling is nearly absent in gastrula lacking both
      maternal and zygotic Laf/Alk8 activity, providing further evidence that Laf/Alk8
      transduces a BMP signal. In total, our work strongly supports the role of
      Laf/Alk8 as a type I BMP receptor required for the specification of ventral cell
      fates.

PMID- 11222142
TI  - A bipotential precursor population for pancreas and liver within the embryonic
      endoderm.
AB  - The pancreas emerges independently from dorsal and ventral domains of embryonic
      gut endoderm. Gene inactivation experiments in mice have identified factors
      required for dorsal pancreas development, but factors that initiate the ventral
      pancreas have remained elusive. In this study, we investigated the hypothesis
      that the emergence of the ventral pancreas is related to the emergence of the
      liver. We find that the liver and ventral pancreas are specified at the same time
      and in the same general domain of cells. Using embryo tissue explantation
      experiments, we find that the default fate of the ventral foregut endoderm is to
      activate the pancreas gene program. FGF signalling from the cardiac mesoderm
      diverts this endoderm to express genes for liver instead of those for pancreas.
      No evidence was found to indicate that the cell type choice for pancreas or liver
      involves a selection for growth or viability. Cardiac mesoderm or FGF induces the
      local expression of sonic hedgehog, which in turn is inhibitory to pancreas but
      not to liver. The bipotential precursor cell population for pancreas and liver in
      embryonic development and its fate selection by FGF has features that appear to
      be recapitulated in the adult pancreas and are reflected in the evolution of
      these organs.

PMID- 11222143
TI  - Hemicentin, a conserved extracellular member of the immunoglobulin superfamily,
      organizes epithelial and other cell attachments into oriented line-shaped
      junctions.
AB  - him-4 mutations cause a novel syndrome of tissue fragility, defective cell
      migration and chromosome instability in Caenorhabditis elegans. Null mutants have
      abnormal escape reflex, mispositioning of the vas deferens and uterus, and
      mitotic chromosome loss and multinucleate cells in the germline. The him-4 gene
      product, hemicentin, is a conserved extracellular matrix protein with 48 tandem
      immunoglobulin repeats flanked by novel terminal domains. Secreted from skeletal
      muscle and gonadal leader cells, hemicentin assembles into fine tracks at
      specific sites, where it contracts broad regions of cell contact into oriented
      linear junctions. Some tracks organize hemidesmosomes in the overlying epidermis.
      Hemicentin tracks facilitate mechanosensory neuron anchorage to the epidermis,
      gliding of the developing gonad along epithelial basement membranes and germline
      cellularization.

PMID- 11222144
TI  - A role for the EphA family in the topographic targeting of vomeronasal axons.
AB  - We have investigated the role of the Eph family of receptor tyrosine kinases and
      their ligands in the establishment of the vomeronasal projection in the mouse.
      Our data show intriguing differential expression patterns of ephrin-A5 on
      vomeronasal axons and of EphA6 in the accessory olfactory bulb (AOB), such that
      axons with high ligand concentration project onto regions of the AOB with high
      receptor concentration and vice versa. These data suggest a mechanism for
      development of this projection that is the opposite of the repellent interaction
      between Eph receptors and ligands observed in other systems. In support of this
      idea, when given the choice of whether to grow on lanes containing EphA
      F(c)/laminin or F(c)/laminin protein (in the stripe assay), vomeronasal axons
      prefer to grow on EphA-F(c)/laminin. Analysis of ephrin-A5 mutant mice revealed a
      disturbance of the topographic targeting of vomeronasal axons to the AOB. In
      summary, these data, which are derived from in vitro and in vivo experiments,
      indicate an important role of the EphA family in setting up the vomeronasal
      projection.

PMID- 11222145
TI  - Expression of activated Ras during Dictyostelium development alters cell
      localization and changes cell fate.
AB  - There is now a body of evidence to indicate that Ras proteins play important
      roles in development. Dictyostelium expresses several ras genes and each appears
      to perform a distinct function. Previous data had indicated that the
      overexpression of an activated form of the major developmentally regulated gene,
      rasD, caused a major aberration in morphogenesis and cell type determination. We
      now show that the developmental expression of an activated rasG gene under the
      control of the rasD promoter causes a similar defect. Our results indicate that
      the expression of activated rasG in prespore cells results in their
      transdifferentiation into prestalk cells, whereas activated rasG expression in
      prestalk causes gross mislocalization of the prestalk cell populations.

PMID- 11222146
TI  - Activation of rabbit oocytes: the impact of the Ca2+ signal regime on
      development.
AB  - Postfertilization manipulation of mammalian embryos results in various
      developmental alterations. To determine whether the manipulation of the Ca2+
      regime causing oocyte activation is a valuable experimental means in helping
      understand the biological process by which embryos integrate signals from outside
      and later regulate gene expression, we linked Ca2+ signal parameters i.e.
      amplitude, number and frequency, with the efficiency and quality of
      postimplantation development. Freshly ovulated rabbit oocytes were subjected to
      repetitive and modulated Ca2+ influx. The results provide three major pieces of
      information. Firstly, the Ca2+ stimulus is the most efficient signal activating
      mammalian eggs when it is applied in a repetitive manner, the amplitude being the
      crucial factor. Secondly, the dynamics of early cleavage does not appear to be
      determined by either the frequency or the amplitude of modulation of the Ca2+
      signal that activates the oocyte. Thirdly, amplitude and temporal modulation of
      the Ca2+ signal in the early minutes influences the developmental performance and
      the morphology of the rabbit parthenogenetic conceptus at day 11.5 of pregnancy.
      The results demonstrate the importance of epigenetic events during
      postfertilization as well as the possible uses of Ca2+ modulation in studying
      long term developmental effects.

PMID- 11222147
TI  - Rescuing desmoplakin function in extra-embryonic ectoderm reveals the importance
      of this protein in embryonic heart, neuroepithelium, skin and vasculature.
AB  - Desmosomes mediate intercellular adhesion through desmosomal cadherins, which
      interface with plakoglobin (PG) and desmoplakin (DP) to associate with the
      intermediate filament (IF) cytoskeleton. Desmosomes first assemble in the E3.5
      mouse trophectoderm, concomitant with establishment of epithelial polarity and
      appearance of a blastocoel cavity. Increasing in size and number, desmosomes
      continue their prominence in extra-embryonic tissues, but as development
      proceeds, they also become abundant in a number of embryonic tissues, including
      heart muscle, epidermis and neuroepithelium. Previously, we explored the
      functional importance of desmosomes by ablating the Dsp gene. Homozygous Dsp
      mutant embryos progressed through implantation, but did not survive beyond E6.5,
      owing to a loss or instability of desmosomes and tissue integrity. We have now
      rescued the extra-embryonic tissues by aggregation of tetraploid (wild-type) and
      diploid (Dsp mutant) morulae. These animals survive several days longer, but die
      shortly after gastrulation, with major defects in the heart muscle,
      neuroepithelium and skin epithelium, all of which possess desmosomes, as well as
      the microvasculature, which does not. Interestingly, although wild-type
      endothelial cells of capillaries do not form desmosomes, they possess unusual
      intercellular junctions composed of DP, PG and VE-cadherin. The severity in
      phenotype and the breadth of defects in the Dsp mutant embryo is greater than PG
      mutant embryos, substantiating redundancy between PG and other armadillo proteins
      (e.g. beta-catenin). The timing of lethality is similar to that of the VE
      cadherin null embryo, suggesting that a participating cause of death may be a
      defect in vasculature, not reported for PG null embryos.

PMID- 11222148
TI  - Regulation of retinal ganglion cell production by Sonic hedgehog.
AB  - Previous work has shown that production of retinal ganglion cells is in part
      regulated by inhibitory factors secreted by ganglion cell themselves; however,
      the identities of these molecules are not known. Recent studies have demonstrated
      that the signaling molecule Sonic hedgehog (Shh) secreted by differentiated
      retinal ganglion cells is required to promote the progression of ganglion cell
      differentiation wave front and to induce its own expression. We present evidence
      that Shh signals play a role to negatively regulate ganglion cell genesis behind
      the differentiation wave front. Higher levels of Shh expression are detected
      behind the wave front as ganglion cells accumulate, while the Patched 1 receptor
      of Shh is expressed in adjacent retinal progenitor cells. Retroviral-mediated
      overexpression of Shh results in reduced ganglion cell proportions in vivo and in
      vitro. Conversely, inhibiting endogenous Shh activity by anti-Shh antibodies
      leads to an increased production of ganglion cells. Shh signals modulate ganglion
      cell production within the normal period of ganglion cell genesis in vitro
      without significantly affecting cell proliferation or cell death. Moreover, Shh
      signaling affects progenitor cell specification towards the ganglion cell fate
      during or soon after their last mitotic cycle. Thus, Shh derived from
      differentiated ganglion cells serves as a negative regulator behind the
      differentiation wave front to control ganglion cell genesis from the competent
      progenitor pool. Based on these results and other recent findings, we propose
      that Shh signals secreted by early-differentiated retinal neurons play dual roles
      at distinct concentration thresholds to orchestrate the progression of retinal
      neurogenic wave and the emergence of new neurons.

PMID- 11222149
TI  - Developmental origin of the rat adenohypophysis prior to the formation of
      Rathke's pouch.
AB  - In amphibians, it has already been shown that the adenohypophysis originates from
      the anterior neural ridge. During the migration and morphogenesis of this organ,
      the anterior neural ridge transiently forms a Rathke's pouch-like structure by
      attaching itself to the rostral tip of the foregut, and finally gives rise to the
      adenohypophysis by detaching from the foregut and becoming connected to the
      infundibulum of the hypothalamus. In order to identify the origin of the
      adenohypophyseal cells in mammalian embryos prior to the formation of Rathke's
      pouch (RP), we labeled the rostral end of the neural plate and the adjacent area
      focally with DiI at the open neurula stage (9.5 dpc). After a 48-hours culture of
      the whole embryos, strongly labeled cells were detected in the RP only when DiI
      was applied to a small area situated just anterior to the rostral end of the
      neural plate. By explanting the labeled RP for a further 7 days, we confirmed
      immunohistochemically that the labeled cells developed into the secretory cells
      of the adenohypophysis. The developmental origin of the adenohypophysis is
      identified for the first time in the early mammalian embryo before the formation
      of RP.

PMID- 11222150
TI  - Biphasic activation of the BMP pathway patterns the Drosophila embryonic dorsal
      region.
AB  - The BMP pathway patterns the dorsal region of the Drosophila embryo. Using an
      antibody recognizing phosphorylated Mad (pMad), we followed signaling directly.
      In wild-type embryos, a biphasic activation pattern is observed. At the cellular
      blastoderm stage high pMad levels are detected only in the dorsal-most cell rows
      that give rise to amnioserosa. This accumulation of pMad requires the ligand
      Screw (Scw), the Short gastrulation (Sog) protein, and cleavage of their complex
      by Tolloid (Tld). When the inhibitory activity of Sog is removed, Mad
      phosphorylation is expanded. In spite of the uniform expression of Scw, pMad
      expansion is restricted to the dorsal domain of the embryo where Dpp is
      expressed. This demonstrates that Mad phosphorylation requires simultaneous
      activation by Scw and Dpp. Indeed, the early pMad pattern is abolished when
      either the Scw receptor Saxophone (Sax), the Dpp receptor Thickveins (Tkv), or
      Dpp are removed. After germ band extension, a uniform accumulation of pMad is
      observed in the entire dorsal domain of the embryo, with a sharp border at the
      junction with the neuroectoderm. From this stage onward, activation by Scw is no
      longer required, and Dpp suffices to induce high levels of pMad. In these
      subsequent phases pMad accumulates normally in the presence of ectopic Sog, in
      contrast to the early phase, indicating that Sog is only capable of blocking
      activation by Scw and not by Dpp.

PMID- 11222151
TI  - Local nonpermissive and oriented permissive cues guide vestibular axons to the
      cerebellum.
AB  - Information that originates from peripheral sensory organs is conveyed by axons
      of cephalic sensory cranial ganglia connecting the sensory organs to appropriate
      central targets in the brain. Thus, the establishment of correct axonal
      projections by sensory afferents is one of the most important issues in neural
      development. Previously, we examined the development of the vestibular nerve that
      originates from the VIIIth ganglion using a flat whole-mount preparation of the
      rat hindbrain and developed an in vitro, culture preparation that can
      recapitulate vestibular nerve development (Tashiro, Y., Endo, T., Shirasaki, R.,
      Miyahara, M., Heizmann, C. W. and Murakami, F. (2000) J. Comp. Neurol. 417, 491
      500). Both in vivo and in vitro, the ascending branch of the VIIIth ganglion
      projecting to the cerebellum reaches the base of the cerebellar primordium and
      starts to splay out towards the rhombic lip, apparently avoiding the ventral
      metencephalon. We now examine the nature of cues that guide vestibulocerebellar
      axons by applying various manipulations to the flat whole-mount in vitro
      preparation. Our observations suggest that local nonpermissive cues and oriented
      cues play a pivotal role in the guidance of vestibular axons to their central
      target.

PMID- 11222152
TI  - Spatially restricted activity of a Drosophila lipid phosphatase guides migrating
      germ cells.
AB  - Temporal and spatial controls of cell migration are crucial during normal
      development and in disease. Our understanding, though, of the mechanisms that
      guide cells along a specific migratory path remains largely unclear. We have
      identified wunen 2 as a repellant for migrating primordial germ cells. We show
      that wunen 2 maps next to and acts redundantly with the previously characterized
      gene wunen, and that known wunen mutants affect both transcripts. Both genes
      encode Drosophila homologs of mammalian phosphatidic acid phosphatase. Our work
      demonstrates that the catalytic residues of Wunen 2 are necessary for its
      repellant effect and that it can affect germ cell survival. We propose that
      spatially restricted phospholipid hydrolysis creates a gradient of signal
      necessary and specific for the migration and survival of germ cells.

PMID- 11222153
TI  - Polycomb group proteins and heritable silencing of Drosophila Hox genes.
AB  - Early in Drosophila embryogenesis, transcriptional repressors encoded by Gap
      genes prevent the expression of particular combinations of Hox genes in each
      segment. During subsequent development, those Hox genes that were initially
      repressed in each segment remain off in all the descendent cells, even though the
      Gap repressors are no longer present. This phenomenon of heritable silencing
      depends on proteins of the Polycomb Group (PcG) and on cis-acting Polycomb
      response elements (PREs) in the Hox gene loci. We have removed individual PcG
      proteins from proliferating cells and then resupplied these proteins after a few
      or several cell generations. We show that most PcG proteins are required
      throughout development: when these proteins are removed, Hox genes become
      derepressed. However, we find that resupply of at least some PcG proteins can
      cause re-repression of Hox genes, provided that it occurs within a few cell
      generations of the loss of repression. These results suggest a functional
      distinction between transcriptional repression and heritable silencing: in at
      least some contexts, Hox genes can retain the capacity to be heritably silenced,
      despite being transcribed and replicated. We propose that silenced Hox genes bear
      a heritable, molecular mark that targets them for transcriptional repression.
      Some PcG proteins may be required to define and propagate this mark; others may
      function to repress the transcription of Hox genes that bear the mark.

PMID- 11222154
TI  - Differential expression and functional analysis of Pitx2 isoforms in regulation
      of heart looping in the chick.
AB  - Pitx2, a bicoid-related homeobox gene, plays a crucial role in the left-right
      axis determination and dextral looping of the vertebrate developing heart. We
      have examined the differential expression and function of two Pitx2 isoforms
      (Pitx2a and Pitx2c) that differ in the region 5' to the homeodomain, in early
      chick embryogenesis. Northern blot and RT-PCR analyses indicated the existence of
      Pitx2a and Pitx2c but not Pitx2b in the developing chick embryos. In situ
      hybridization demonstrated a restricted expression of Pitx2c in the left lateral
      plate mesoderm (LPM), left half of heart tube and head mesoderm, but its absence
      in the extra-embryonic tissues where vasculogenesis occurs. RT-PCR experiments
      revealed that Pitx2a is absent in the left LPM, but is present in the head and
      extra-embryonic mesoderm. However, ectopic expression of either Pitx2c or Pitx2a
      via retroviral infection to the right LMP equally randomized heart looping
      direction. Mapping of the transcriptional activation function to the C terminus
      that is identical in both isoforms explained the similar results obtained by the
      gain-of-function approach. In contrast, elimination of Pitx2c expression from the
      left LMP by antisense oligonucleotide resulted in a randomization of heart
      looping, while treatment of embryos with antisense oligonucleotide specific to
      Pitx2a failed to generate similar effect. We further constructed RCAS retroviral
      vectors expressing dominant negative Pitx2 isoforms in which the C-terminal
      transcriptional activation domain was replaced by the repressor domain of the
      Drosophila Engrailed protein (En(r)). Ectopic expression of Pitx2c-En(r), but not
      Pitx2a-En(r), to the left LPM randomized the heart looping. The results thus
      demonstrate that Pitx2c plays a crucial role in the left-right axis determination
      and rightward heart looping during chick embryogenesis.

PMID- 11222155
TI  - A lesson from flex: consider the Y chromosome when assessing Drosophila sex
      specific lethals.
AB  - Bhattacharya et al. (Bhattacharya, A., Sudha, S., Chandra, H. S. and Steward, R.
      (1999) Development 126, 5485-5493) reported that loss-of-function mutations in
      the flex (female-specific lethal on X) gene caused female-specific lethality
      because flex(+) acts as a positive regulator of the master switch gene Sex lethal
      (Sxl). Sxl is essential for female development. Key to their conclusion was the
      ability of flex mutations to suppress the male lethality caused by Sxl(M)
      mutations, which inappropriately activate Sxl female-specific expression. Here we
      report our contrary findings that flex mutations fail to suppress even the
      weakest Sxl(M )alleles, arguing against the proposed regulatory relationship
      between flex and Sxl. Instead we show that the lethal flex phenotype depends on
      the absence of a Y chromosome, not on the presence of two X chromosomes. flex
      lethality is caused by a defect in the functioning of the X-linked rDNA locus
      called bobbed, since this defect is complemented by the corresponding wild-type
      rDNA complex on the Y.

PMID- 11222156
TI  - [Diagnostic usefulness of Alcohol Use Disorders Identification Test (AUDIT) for
      detecting hazardous alcohol consumption in primary care settings].
AB  - BACKGROUND: To evaluate the diagnostic usefulness of AUDIT (Alcohol Use Disorders
      Identification Test) for detecting hazardous alcohol consumption in primary care
      settings, to assess the potential differences according to age or sex and to
      compare its diagnostic value with that of other conventionally used measures
      (CAGE questionnaire and biological markers). PATIENTS AND METHOD: This is a
      descriptive cross-sectional study for evaluation of diagnostic tests with 500
      participating patients randomly selected among those attending a family health
      care center. Data about alcohol intake were collected using a semistructured
      interview, considering as hazardous alcohol consumption a weekly intake of 35
      SDUs (standard drink unit) or above for men and 21 for women. AUDIT and CAGE
      questionnaires were administered and blood levels of GGT, MCV, AST, ALT, alkaline
      phosphatase, platelets, tryglicerides and uric acid were determined. For each one
      of those sensitivity, specificity, global value, predictive values, positive and
      negative probability ratio were calculated as well as ROC analysis for the
      questionnaires. RESULTS: Sensitivity of AUDIT in detecting current hazardous
      drinkers was 89%, specificity was 93% and area under ROC was 0.98 (95% CI, 0.96
      0.99). Its sensitivity was found to be lower in the female group (60 vs. 78%) as
      well as for age group under 60 years (86 vs. 100%). CAGE questionnaire showed a
      sensitivity of 48% and a specificity of 97%. Biological markers offered
      sensitivities lower than 40% and specificities over 90%. CONCLUSIONS: AUDIT is a
      useful tool for detecting hazardous alcohol consumption in ambulatory care. Its
      sensitivity being lower for women and its diagnostic usefulness significantly
      exceeding that of other screening measures commonly used.

PMID- 11222157
TI  - [Risk of hepatitis B virus transmission from hepatitis B core antibody-positive
      liver donors].
AB  - BACKGROUND: To study the hepatitis B virus (HBV) transmission from donors HBsAg
      /AntiHBc+ to liver transplant recipients. PATIENTS AND METHOD: We studied
      retrospectively the HBV serological markers in 43 donors from our center and also
      the serological condition of the 41 recipients. The HBV serological markers were
      analyzed by ELISA and HBV DNA was detected by hybridation assays. RESULTS: 13
      donors samples showed some HBV serological markers: 6 anti-HBc and anti- HBs
      (13.9%), 4 anti-HBc (9%) and 3 anti- HBs (6.9%). There were no cases of hepatitis
      B among liver recipients from donors with negative serological markers. Among the
      13 recipients with HBV serological markers, 9 were followed during 39 (SD 17)
      months. The 5 recipients with no HBV markers, who received an anti- HBc+ with or
      without anti- HBs (100%) developed hepatitis B. The two liver recipients with
      anti-HBs solely, did not developed infection (0%). Of the 41 recipients, 15 had
      some HBV markers before transplant and two of them received an anti-HBc+ and did
      not develop the infection (0%). CONCLUSIONS: In our study, the prevalence of
      serological HBV infection in donors and recipients was of 30.2 and 31.7%,
      respectively. Anti-HBc with or without anti-HBs donors transmitted the HBV
      infection in all the cases (100%) to the susceptible recipients. The presence of
      anti-HBs in recipients protected these against the infection. Only the anti-HBs
      positive donors did not trasmit the HBV infection.

PMID- 11222158
TI  - [Food consumption and nutrient intake in relation to smoking].
AB  - BACKGROUND: It is well known that smoking and some nutritional habits are two of
      the most important risk factors for the development of certain cancers and
      cardiovascular diseases. The purpose of this study is to assess the food and
      nutrient consumption in relation to smoking in the Catalan population, Spain.
      SUBJECTS AND METHOD: A representative sample of the Catalan population of 1774
      people aged 18 to 64 years from both sexes. Nutritional status was evaluated
      using selected anthropometrical indexes, and food consumption with two 24-hour
      recall. Questionnaires about smoking consumption and a semiquantitative frequency
      questionnaire about alcohol consumption were also administered. RESULTS: Male non
      smokers consumed more dairy products than smokers, and more fruits and nuts than
      smokers and ex-smokers. Female non-smokers consumed more chicken, fruits and less
      sweets than smokers and ex-smokers. In both genders, smokers consumed more
      alcohol. With respect to nutrients, smokers consumed less fiber than non smokers
      and more energy from lipids and saturated and monounsaturated fatty acids.
      CONCLUSIONS: The diet of smokers is less healthy than that of non smokers and ex
      smokers, which indicates a higher risk for the incidence of certain cancers and
      cardiovascular diseases.

PMID- 11222159
TI  - [Phlebitis due to intravenous administration of macrolide antibiotics. A
      comparative study of erythromycin versus clarithromycin].
AB  - BACKGROUND: To know and to compare the incidence of phlebitis due to intravenous
      administration of macrolide antibiotics erythromycin and clarithromycin. PATIENTS
      AND METHOD: Non-randomized prospective study of consecutive patients who were
      diagnosed of community pneumonia and treated with intravenous macrolides (19 with
      erythromycin and 25 with clarithromycin). RESULTS: The cumulative incidence of
      phlebitis in patients treated with erythromycin was 78.9% (incidence rate of 0.40
      episodes/patient-day) and in those treated with clarithromycin 76% (incidence
      rate of 0.35 episodes/patient-day). CONCLUSIONS: The risk of phlebitis is high
      and similar with intravenous administration of both macrolides.

PMID- 11222160
TI  - [Role of primary care in problems derived from alcohol consumption].

PMID- 11222162
TI  - [Eutanasia and palliative care: dangerous friends].

PMID- 11222161
TI  - [Identification and characterization of the first Spanish familial ligand
      defective apolipoprotein B homozygote].
AB  - BACKGROUND: Familial ligand-defective apolipoprotein B 100 (FDB) is an autosomal
      inherited disease due to mutations on apo B 100, clinically indistinguishable
      from familial hypercholesterolemia (FH). We described the first Spanish
      homozygote for FDB. METHODS: We have screened R3500Q mutation of apo B gene (PCR
      SSCP analysis) in a large family with FDB and have identified the first Spanish
      homozygote for FDB. RESULTS: The homozygote is a 58 year-old man with coronary
      heart disease, no presence of xanthomata and with total cholesterol and LDL
      cholesterol plasma levels of 415 and 352 mg/dl. The response to statins and
      resins was up to 42% for total cholesterol and 51% for LDLc plasma values. The
      LDL receptor activity was normal in the FDB homozygote. CONCLUSIONS: We have
      identified and characterised the first Spanish homozygote for FDB (R3500Q
      mutation). Our data indicate a moderate lipoprotein phenotype in FDB homozygote,
      different as expected comparing to homozygous FH.

PMID- 11222163
TI  - [A diagnostic algorithm for ferropenia].

PMID- 11222164
TI  - [Methadone maintenance programs effectiveness. An outcome evaluation studies
      review].

PMID- 11222165
TI  - [Syndrome of hypersensitivity by antiepileptic drugs].

PMID- 11222166
TI  - [The impact of a itinerant market on emergency department visits].

PMID- 11222167
TI  - [Pulmonary hyalinizing multiple granuloma].

PMID- 11222168
TI  - [Chronic treatment of advanced and terminal neoplastic disease].

PMID- 11222169
TI  - [Useless catheterization in an emergency service].

PMID- 11222171
TI  - [Prospective study of 221 community acquired pneumonias followed up in an
      outpatient clinic. Etiology and clinical-radiological progression].
AB  - BACKGROUND: All the community acquired pneumonia followed up in an outpatient
      clinic were prospectively studied in order to determine: etiology, clinical
      radiological characteristics and its progression with diagnostic and therapeutic
      protocols. PATIENTS AND METHOD: We arranged clinical evaluation protocols,
      etiological diagnosis by means of serology (in the first visit and three weeks
      later); and when necessary, by means of fiberbronchoscopy (protected
      microbiological brush), as well as clinical and radiological progression (up to
      three visits) after empirical treatment. RESULTS: Initially, 240 patients were
      included, of which 221 were fully followed up. Etiological diagnosis was obtained
      in 86 patients (39%). The bacteria most frequently isolated was Coxiella burnetii
      (12.2%), followed up Mycoplasma pneumoniae and Legionella pneumophila. Two cases
      of Strepcococus pneumoniae were diagnosed. The most frequent radiological onset
      was alveolar infiltrate (86%). The initial empiric treatment were macrolids (71%)
      or second generation cephalosporines (22%). Most patients presented a favourable
      clinical and radiological progression. Only 2 patients needed admission to the
      hospital (< 1%). CONCLUSIONS: In community acquired pneumonias studied in our
      outpatient clinic we found a high number of "atypical" agents. Treatment with
      macrolids or second generation cephalosporines are appropriate for these
      patients.

PMID- 11222172
TI  - [Diagnosis and treatment of tuberculosis in Spain: results of the Multicenter
      Project for Tuberculosis Research].
AB  - BACKGROUND: To analyze clinical practice regarding tuberculosis in Spain.
      MATERIAL AND METHOD: After active search in 14 registries, cases of tuberculosis
      were identified in 13 autonomous regions, representing almost 67% of the total
      Spanish population. The study period was May 1996-April 1997. RESULTS: 10,053
      cases were identified. Almost 80% were diagnosed at the hospital and most of the
      patients (91.7%) were symptomatic. Median patient delay was 21 days and median
      delay between symptoms and treatment was 41 days. Smear and culture was performed
      in 82% of pulmonary cases while at least a culture was performed in 75.5% of
      extrapulmonary cases. 72.5% of pulmonary cases and 39.7% of extrapulmonary cases
      were culture positive. More than 76% of the subjects were treated with 3 drugs,
      generally rifampin, isoniazid and pirazinamide in agreement with Spanish
      guidelines; however, the information on duration of treatment was insuficient.
      Combined tablets were usually prescribed (86.8% of patients) and use of DOT was
      scarce (5.4% of cases). The information on contact investigation was poor.
      CONCLUSIONS: Diagnostic and treatment practices regarding tuberculosis have
      clearly improved in Spain, but patient management has still to improve.

PMID- 11222173
TI  - [Incidence and survival of leukemias according to the different histologic
      subsets, in Tarragona, Spain, between 1980-1994].
AB  - BACKGROUND: To study the incidence and survival of leukemias according to the
      different histologic types in Tarragona, Spain. MATERIAL AND METHOD: Analysis of
      the information obtained from the Cancer Registry of Tarragona (Spain) between
      1980-1994. The leukemias were classified in: acute lymphoblastic leukemia (ALL),
      acute myelogenous leukemia (AML), chronic lymphoid leukemia (CLL) and chronic
      myeloid leukemia (CML). The estimated incidence rates have been adjusted to the
      worldwide population, the percentage of the incidence annual change through
      Poisson regression models and the relative survival using the registry of death
      rate of Catalonia. RESULTS: The adjusted rate for leukemias between the period
      1990-1994 was 8.0 per 100,000 inhabitants in men and of 5.2 in women, being the
      CLL the most frequent subtype. Regarding the trend of incidence an increase of
      the CLL of 2.2% annual (CI 95%, 0.1-6.6) in men and of 7.7% (CI 95%, 1.4-14.4) in
      women was observed. In the remaining subtypes, there was no trend, but the non
      classified leukemias decreased a -10.8% annual (CI 95%, -15.0 to -6.4) in men and
      a -9.9% annual (CI 95%, 15.4 to -4.0) in women. 5-year relative survival (RS5y)
      for the total leukemias was 37.7% in men and 45.3% in women. It stands out the
      CLL with a RS5y of 64.8% in men and of 75.7% in women and childhood ALL with a
      RS5y of 83.0% in boys and of 84.9% in girls. CONCLUSIONS: In Tarragona, Spain, an
      increase of the CLL incidence has been observed suggesting an improvement in the
      diagnosis, parallel to a decrease of the non-classified leukemias. The survival
      in this cohort of patients was similar to the that reported in other european
      registries.

PMID- 11222174
TI  - [Etiology and management evaluation of community acquired pneumonia].

PMID- 11222175
TI  - [Exposure to Mycobacterium tuberculosis during a bus travel].
AB  - BACKGROUND: In an outbreak of tuberculosis that occurred in a school, we
      evaluated the possible transmission during a trip in a school bus as the cause of
      infection. SUBJECTS, PATIENTS AND METHODS: Contact tracing of the driver, 3
      teachers and 49 students from different grades who were travelling from Malaga to
      Sierra Nevada (Spain) in March 1998. All the students from the ten grades where
      any case of tuberculosis appeared from April to December 1998 and all the
      teachers of the school were included. RESULTS: At the school, 232 students were
      studied. The prevalence of the infection was 35%. A total of 12 new cases among
      the students were found. No teachers out of the 127 examined became ill. Out of
      the people who travelled by school bus, 2 teachers and 19 students were infected,
      prevalence among students 46%; five of those become ill. The odds ratio of
      infection for those having a class mate with positive smears was 5,5. On the
      other hand, the trip by bus (compared with those who did not take it) meant a
      odds ratio of 3,4. Most of the infected travellers were sitting in the bus close
      to the index case. CONCLUSIONS: In this tuberculosis outbreak some of the
      students who became ill or infected were not near the index case nor friendly
      with him at class. Therefore is possible that in some cases tuberculosis was
      transmitted inside the bus.

PMID- 11222176
TI  - [The end of life: could it be comfortable?].

PMID- 11222177
TI  - [Molecular biology of hepatitis C virus: implications for the development of new
      therapies and prophylactic vaccine].

PMID- 11222178
TI  - [Adrenal carcinoma and spinal epidural lipomatosis].

PMID- 11222179
TI  - [Internal calls to the emergency team of medical area].

PMID- 11222182
TI  - Information transfer: radiology reports.

PMID- 11222180
TI  - [Short term benefit of genotype resistance testing].

PMID- 11222183
TI  - The molecular genetic revolution in congenital heart disease.

PMID- 11222184
TI  - House call.

PMID- 11222186
TI  - Radiology reports: examining radiologist and clinician preferences regarding
      style and content.
AB  - OBJECTIVE: The introduction of picture archiving and communication systems (PACS)
      frequently includes the option of computer-generated itemized reports. This
      motivated us to reassess the merits of traditional prose dictated reports. This
      study examines radiologist and clinician preferences regarding report style and
      content. MATERIALS AND METHODS: The study was conducted in two parts. The first
      part was a retrospective audit of existing medical imaging prose reports to
      determine their content. The second part comprised a questionnaire containing
      three mock clinical scenarios. Three pairs of reports were provided for each
      scenario, with only essential information in the first pair, some optional
      information in the second, and the most complete report in the third. Each pair
      consisted of a prose and itemized report with identical content. Participants
      ranked reports by preference and were asked specific questions regarding report
      content. The questionnaires were mailed to referring clinicians and administered
      during an interactive forum to staff radiologists, radiology fellows, and
      radiology residents. RESULTS: The audit of existing reports showed a wide
      variation in all fields with consistency limited to a given radiologist.
      Responses to the questionnaire showed that, in general, a majority of
      radiologists and referring clinicians preferred itemized reports. The itemized
      report with the most detailed content was ranked highest of all three scenarios.
      CONCLUSION: Prose reports foster a lack of standardization of content among
      different radiologists. Itemized reports facilitate complete documentation of
      information and measurements and are more popular with both radiologists and
      referring clinicians.

PMID- 11222185
TI  - Quantitative and qualitative evaluation of volume of low osmolality contrast
      medium needed for routine helical abdominal CT.
AB  - OBJECTIVE: The purpose of our study was to determine the minimum optimal dose of
      IV contrast medium for helical CT that can preserve image quality while reducing
      cost. SUBJECTS AND METHODS: Four hundred sixty-three patients from six centers
      were enrolled in a prospective trial in which patients were randomized into one
      of four weight-based dose categories of iopromide, 300 mg I/mL: 1.25, 1.50, 1.75,
      and 2.0 mL/kg. Six of 463 patients were excluded from analysis. A radiologist at
      each center who was unaware of the volume of contrast medium administered
      determined whether the scans were acceptable. The responses were analyzed by
      dose, in aggregate, and by weight. Enhancement values (in Hounsfield units) in
      regions of interest in the liver, pancreas, aorta, and kidneys were obtained at a
      single time during the scan. The participating radiologist was unaware of these
      values. Finally, three additional nonparticipating site observers assessed the
      images for acceptability, diagnostic quality, and overall level of confidence. A
      cost model comparing incurred charges in using 150 or 100 mL, or 1.5 mL/kg, of
      low osmolality contrast medium was developed from experience in an additional 303
      patients. RESULTS: We found no clinically significant difference in acceptability
      of scans at doses greater than 1.5 mL/kg. However, significant variability
      occurred among the centers. The use of 1.5 mL/kg led to a savings of $9927.16 for
      303 patients when compared with the use of 150 mL at list price. The cost is the
      same for 1.5 mL/kg or use of 100 mL of contrast medium. CONCLUSION: A weight
      based dose at 1.5 mL/kg of low osmolality contrast medium can provide acceptable
      scans in most patients, with a significant cost savings.

PMID- 11222187
TI  - The HIV-positive patient and confidentiality.

PMID- 11222188
TI  - The ability of helical CT to preoperatively stage endometrial carcinoma.
AB  - OBJECTIVE: This study evaluated helical CT as an imaging modality for
      preoperative staging of endometrial carcinoma. MATERIALS AND METHODS: Three
      radiologists retrospectively and independently reviewed the preoperative helical
      CT scans of 25 consecutive patients with endometrial carcinoma. The presence or
      absence of deep myometrial invasion and the presence or absence of cervical
      involvement were evaluated on helical CT and compared with pathologic findings at
      hysterectomy. RESULTS: Helical CT has a sensitivity of 83% and a specificity of
      42% for the detection of deep myometrial invasion (stage IC). Helical CT has a
      sensitivity of 25% and a specificity of 70% for the detection of cervical
      involvement (state II). These results compare poorly with those of MR imaging
      (sensitivity 92%, specificity 90% for the detection of deep myometrial invasion;
      sensitivity 86%, specificity 97% for the detection of cervical involvement).
      CONCLUSION: Helical CT is insensitive and nonspecific compared with MR imaging
      for the preoperative staging of endometrial carcinoma. MR imaging remains the
      imaging modality of choice.

PMID- 11222189
TI  - Hemorrhage during pregnancy: sonography and MR imaging.

PMID- 11222190
TI  - Endometrial polyps: sonohysterographic evaluation.

PMID- 11222191
TI  - Vaginitis emphysematosa: CT and review of the literature.
AB  - OBJECTIVE: This report describes the CT appearance of vaginitis emphysematosa.
      CONCLUSION: Vaginitis emphysematosa is characterized by gas-filled cysts in the
      vaginal wall, in a pattern similar to pneumatosis of the intestines or bladder.
      This bacterial vaginitis is benign and self-limited and does not signify the
      presence of tissue necrosis or life-threatening infection.

PMID- 11222193
TI  - Collecting duct carcinoma of the kidney: are imaging findings suggestive of the
      diagnosis?
AB  - OBJECTIVE: Collecting duct carcinoma derives from the renal medulla and has an
      infiltrative growth pattern at pathologic examination. The purpose of our study
      was to characterize the imaging features of this aggressive malignancy and
      determine whether the diagnosis can be reliably suggested from imaging findings.
      MATERIALS AND METHODS: Radiologic studies from 17 patients with pathologically
      proven collecting duct carcinoma were analyzed by two reviewers. RESULTS: The
      tumors varied in size from 1.5 to 19 cm (mean, 7.7 cm). Medullary involvement was
      present on CT in 16 (94%) of 17 cases, but cortical involvement or an exophytic
      component was also present in 15 cases (88%) and 10 cases (59%), respectively.
      The reniform contour of the kidney was preserved in seven cases (41%) and
      correlated with a smaller tumor size (p<0.01). Tumors showed an infiltrative
      appearance on CT in 11 cases (65%), but an expansile component was also present
      in eight of these cases. A cystic component was present on CT in six (35%) of 17
      cases. On sonography, the solid tumor component was hyperechoic to normal renal
      parenchyma in six of seven cases and isoechoic in the other. On MR imaging, all
      tumors (4/4) were hypointense on T2-weighted imaging. On urography, all lesions
      (5/5) distorted the intrarenal collecting system. On angiography, all tumors
      (3/3) were hypovascular. CONCLUSION: Medullary involvement and an infiltrative
      appearance are common findings on cross-sectional imaging and may suggest the
      diagnosis of collecting duct carcinoma. In large tumors, however, these features
      are frequently overshadowed by an exophytic or expansile component that cannot be
      distinguished from the more common cortical renal cell carcinoma.

PMID- 11222194
TI  - Evaluating the CT diagnosis of Clostridium difficile colitis: should CT guide
      therapy?
AB  - OBJECTIVE: The purpose of this study was to further characterize the CT findings
      of Clostridium difficile colitis and to provide for the first time a diagnostic
      sensitivity, specificity, positive predictive value, and negative predictive
      value to help clinicians decide whether antibiotic treatment is warranted on the
      basis of CT findings while awaiting stool test results (which may take as long as
      48 hr). MATERIALS AND METHODS: A retrospective review covering a 4-year period
      was performed of the charts and CT scans of 54 symptomatic patients with stool
      test results positive for C. difficile and of a control group of 56 patients with
      antibiotic-associated diarrhea with stool test results negative for C. difficile.
      RESULTS: At our institution, C. difficile colitis was explicitly diagnosed at CT
      in these patients with a sensitivity of 52%, specificity of 93%, positive
      predictive value of 88%, and negative predictive value of 67%. The sensitivity
      can be raised to 70% with no change in specificity with more rigid adherence to
      diagnostic criteria of colon wall thickening of greater than 4 mm combined with
      any one or more findings of pericolonic stranding, colon wall nodularity, the
      "accordion" sign, or otherwise unexplained ascites. CONCLUSION: Although routine
      CT screening of antibiotic-associated diarrhea is not advocated, the 88% positive
      predictive value of a diagnosis of C. difficile colitis in those who are scanned
      may merit consideration of treatment by clinicians on the basis of the CT results
      alone.

PMID- 11222196
TI  - Defecographic measurements of rectal intussusception and prolapse in patients and
      in asymptomatic subjects.
AB  - OBJECTIVE: The aim of this study was to provide measurements for the
      defecographic diagnosis of rectal intussusception and rectal prolapse. MATERIALS
      AND METHODS: Four hundred thirty-seven consecutive patients with defecation and
      micturition disorders and gynecologic complaints were studied by means of
      defecography (120 patients), colpodefecography (17 patients), or
      cystocolpodefecography (300 patients). As a control group, 43 asymptomatic
      subjects underwent defecographic examination. RESULTS: Thirty-five patients were
      found to have rectal intussusception and 18, to have rectal prolapse. Anterior
      and posterior rectal wall folding thickness, intussuscipiens diameter,
      intussusceptum lumen diameter, and the ratio between the intussuscipiens diameter
      and the intussusceptum lumen diameter were measured in all patients. The findings
      were compared with those obtained in 13 of 43 asymptomatic subjects with rectal
      outline changes mimicking intussusception. Rectal folding thickness and the ratio
      between the intussuscipiens diameter and the intussusceptum lumen diameter were
      significantly greater in subjects with rectal intussusception and rectal prolapse
      than in asymptomatic subjects with rectal mucosa folding. CONCLUSION: Our
      findings suggest that dynamic evacuation radiology contributes to making a
      differential diagnosis between rectal intussusception and mucosal folds in the
      rectum.

PMID- 11222197
TI  - Digital subtraction bowel cleansing in CT colonography.

PMID- 11222198
TI  - CT of angioedema of the small bowel.
AB  - OBJECTIVE: The purpose of this study was to determine the added diagnostic value
      of CT for the diagnosis of visceral angioedema. CONCLUSION: Thickening of the
      small-bowel wall and mucosa with increased contrast enhancement, depiction of
      more layers of the small-bowel wall than normal, prominent mesenteric vessels,
      ascites, and fluid accumulation in the small bowel or together in the small bowel
      and the colon were the most significant CT findings in three patients with
      visceral angioedema. Findings appear to be transient.

PMID- 11222199
TI  - Tissue harmonic imaging: is it a benefit for bile duct sonography?
AB  - OBJECTIVE: Our purpose was to compare tissue harmonic imaging with conventional
      sonography of the biliary tract. SUBJECTS AND METHODS: Eighty patients with
      suspect biliary disease had conventional sonography and tissue harmonic imaging
      with an ATL 3000 or 5000 scanner in a 6-month interval. Final diagnoses included
      malignant biliary obstruction (n = 30), choledocholithiasis (n = 16), sclerosing
      cholangitis (n = 4), normal or nonobstructed ducts (n = 16), and miscellaneous
      conditions (n = 14). Similar images were taken with each technique in terms of
      projection, field of view, focal zone selection, and evidence of disease. Two
      separate observers blinded to patient data and technique reviewed and graded
      images individually for the appearance of the lumen of the bile ducts, the length
      of the visible duct, the appearance of the duct wall, the presence of any
      intraluminal masses, and the appearance of associated acoustic shadows. Images
      were graded from zero to 3, with 3 being the best. RESULTS: The median of the 546
      tissue harmonic images was one grade higher than the median for the corresponding
      conventional images (p < 0.0001). Improvements with tissue harmonic imaging
      included better sharpness of the duct walls (p < 0.01), a clearer lumen (p <
      0.0001), identification of a longer length of the common bile duct (p < 0.0001),
      and improved detection of intraluminal masses (p < 0.006). Acoustic shadows were
      better defined and blacker with tissue harmonic imaging (p < 0.007). CONCLUSION:
      Improvement in contrast and reduction of side lobe artifacts with tissue harmonic
      imaging enhance visualization of the biliary ducts. Tissue harmonic imaging is
      now our routine technique for bile duct examination.

PMID- 11222201
TI  - Contrast-enhanced subtraction harmonic sonography for evaluating treatment
      response in patients with hepatocellular carcinoma.
AB  - OBJECTIVE: Our objective was to assess the usefulness of contrast-enhanced
      subtraction harmonic sonography in evaluating the treatment response of patients
      with hepatocellular carcinoma. SUBJECTS AND METHODS: Thirty-two hepatocellular
      carcinoma lesions in 26 patients (age range, 44-85 years; mean age, 66 years)
      were examined with Levovist-enhanced intermittent harmonic imaging before and
      after therapy. A Toshiba Powervision 8000 was used. A subtraction image was
      obtained by digitally subtracting the last-frame harmonic image from the first
      frame image when multishot mode was preset. Results of contrast-enhanced CT were
      compared with the results of subtraction harmonic imaging. RESULTS: Before
      therapy, an enhancement pattern of tumor vascularity was seen for 93.8% (30/32)
      of hepatocellular carcinoma nodules on subtraction harmonic imaging. After
      therapy, subtraction harmonic imaging showed 46.7% (14/30) enhancement
      (incomplete tumor necrosis) and 53.3% (16/30) no enhancement (complete tumor
      necrosis). When dynamic CT was the gold standard, the sensitivity, specificity,
      and accuracy of subtraction harmonic imaging were 93.3%, 100%, and 96.7%,
      respectively. Intratumoral flow signals in hepatocellular carcinoma after therapy
      on harmonic imaging were used as a guide to target additional percutaneous
      therapy. CONCLUSION: Digital subtraction contrast-enhanced harmonic imaging can
      depict tumor vascularity in hepatocellular carcinoma after therapy sensitively
      and accurately. Because it is easy to perform and provides real-time needle
      insertion guidance, it may be preferable to perform after localized therapy to
      monitor treatment response, which will reduce unnecessary CT scanning.

PMID- 11222202
TI  - Hepatic perfusion parameters in chronic liver disease: dynamic CT measurements
      correlated with disease severity.
AB  - OBJECTIVE: The aim of our study was to determine if hepatic perfusion parameters
      measured with CT change in relation to disease severity in patients with chronic
      liver disease. SUBJECTS AND METHODS: Dynamic contrast-enhanced single-section CT
      scans of the liver were obtained in 40 individuals who included six control
      subjects, 16 patients with noncirrhotic chronic liver disease, and 18 patients
      with cirrhosis. Hepatic, aortic, and portal venous time-density curves were
      fitted to a dual-input one-compartment model to calculate the liver perfusion,
      arterial fraction, distribution volume, and mean transit time. RESULTS: Liver
      perfusion decreased in patients with cirrhosis (67 +/- 23 mL. min(-1). 100 mL(-1)
      versus 108 +/- 34 mL. min(-1). 100 mL(-1) in control subjects [p = 0.009] and 98
      +/- 36 mL. min(-1). 100 mL(-1) in patients with noncirrhotic chronic liver
      disease [p = 0.003]), and the arterial fraction and the mean transit time
      increased (41 +/- 27% and 51 +/- 79 sec versus 17 +/- 16% and 16 +/- 5 sec in
      control subjects, and 19 +/- 6% and 17 +/- 8 sec in patients with noncirrhotic
      chronic liver disease [p < 0.05]). A significant correlation was seen between
      these three perfusion parameters and the severity of chronic liver disease based
      on clinical and biologic data (p < 0.001). No significant change in distribution
      volume was observed. CONCLUSION: Hepatic perfusion parameters measured with CT
      were significantly altered in cirrhosis and correlated with the severity of
      chronic liver disease.

PMID- 11222204
TI  - Dynamic CT of hepatic abscesses: significance of transient segmental enhancement.
AB  - OBJECTIVE: The purpose of this study was to evaluate dynamic CT findings of
      hepatic abscesses, especially segmental hepatic enhancement, and to clarify the
      cause. MATERIALS AND METHODS: Twenty-four abscesses in eight patients were
      examined by early (30 sec) and late phase (90 sec) dynamic CT. Patients underwent
      abscess drainage (n = 1), hepatic resection (n = 2), or antibiotic therapy (n =
      5). CT during arterial portography and CT during hepatic arteriography were
      performed in one patient. We retrospectively observed the frequency and changes
      of segmental hepatic enhancement on dynamic CT and determined its cause using
      radiologic and pathologic correlation. RESULTS: Sixteen abscesses (67%) showed
      transient segmental hepatic enhancement and three abscesses showed only segmental
      hepatic enhancement in the early phase. Four abscesses in one patient who
      underwent CT during arterial portography and CT during hepatic arteriography
      showed a segmental perfusion defect on CT during arterial portography and
      segmental enhancement on CT during hepatic arteriography. On follow-up dynamic CT
      performed 10-17 days after the initial CT, segmental hepatic enhancement
      surrounding hepatic abscesses decreased or disappeared in all abscesses.
      Pathologic examination of two patients showed marked inflammatory cell
      infiltration with stenosis of portal venules within the portal tracts surrounding
      hepatic abscesses without definite inflammation in the liver parenchyma.
      CONCLUSION: Segmental hepatic enhancement on dynamic CT is frequently associated
      with hepatic abscesses and may be caused by decreased portal flow resulting from
      inflammation of the portal tracts.

PMID- 11222205
TI  - Targeted transarterial oily chemoembolization for small foci of hepatocellular
      carcinoma using a unified helical CT and angiography system: analysis of factors
      affecting local recurrence and survival rates.
AB  - OBJECTIVE: We assessed the local recurrence rate after a single targeted
      transarterial oily chemoembolization for small hepatocellular carcinoma with the
      unified helical CT and angiography system and analyzed the factors affecting the
      local recurrence rate and survival rate with Cox proportional hazards model.
      MATERIALS AND METHODS: For 54 consecutive patients with 71 small hepatocellular
      carcinomas (< or = 5 cm) with no more than two associated lesions, targeted oily
      chemoembolization was performed with an emulsion of doxorubicin hydrochloride
      mixed with iodized oil or a suspension of zinostatin stimalamer followed by
      gelatin sponge particles. When local recurrence or a new lesion appeared, follow
      up targeted oily chemoembolization was performed. RESULTS: For 52 of 71 lesions,
      the catheterization to a subsegmental or more distal feeding artery could be
      performed. Local recurrence was recognized in 33.2% at 1 year and 37.8% at 2 and
      3 years. The significant factors that affected local recurrence were tumor size
      (p = 0.005) and degree of deposition of iodized oil within the lesion (p =
      0.049). The survival rates at 1, 2, and 3 years were 93.3%, 77.1%, and 77.1%,
      respectively. The significant factors affecting survival rate were tumor thrombus
      in large vessels (p = 0.0001), appearing after the first chemoembolization, and
      maximum tumor size (p = 0.022). CONCLUSION: Single targeted transarterial oily
      chemoembolization with the unified helical CT and angiography system had a low
      local recurrence rate for small hepatocellular carcinoma, and follow-up
      embolization resulted in a good survival rate. Tumor size along with degree of
      intratumoral iodized oil deposition and tumor thrombus along with maximum tumor
      size were significant factors affecting local recurrence and survival rate,
      respectively.

PMID- 11222206
TI  - Multidetector CT of the pancreas and bile duct system: value of curved planar
      reformations.

PMID- 11222207
TI  - Pancreatic parenchymal metastases: observations on helical CT.

PMID- 11222208
TI  - Role of chest CT in the follow-up of ovarian adenocarcinoma.
AB  - OBJECTIVE: We describe the prevalence of metastatic chest disease in ovarian
      adenocarcinoma as seen on CT. We sought to determine whether routine chest CT
      added any pertinent information to the follow-up examination of patients with
      ovarian adenocarcinoma. MATERIALS AND METHODS: Retrospective review of our tumor
      registry yielded 96 patients with ovarian adenocarcinoma who had only a single
      primary malignancy and at least one CT scan of the chest, abdomen, and pelvis. CT
      scans were reviewed to assess the presence of metastatic chest disease in
      relation to disease activity in the abdomen and pelvis. Chest CT findings were
      correlated with the physical examination findings and CA-125 levels and were
      reviewed in consultation with a gynecologic oncologist to select only those
      patients with chest abnormalities attributable to metastatic disease. RESULTS: A
      total of 266 CT scans were obtained. Forty (41.7%) of the 96 patients had
      abnormalities attributable to metastatic chest disease on one or more scans. In
      the absence of disease progression in the abdomen and pelvis, chest disease
      progression was seen in only six (2.7%) of the 226 follow-up CT scans. Five of
      the six patients had rising CA-125 levels. CONCLUSION: Correlation of the
      findings of abdominal and pelvic CT with the physical findings and the CA-125
      levels serves as effective follow-up in patients with ovarian adenocarcinoma. The
      contribution of additional chest CT in these patients is small.

PMID- 11222209
TI  - Focal abnormalities of the trachea and main bronchi.

PMID- 11222210
TI  - Unilateral absence of pulmonary perfusion mimicking pulmonary embolism.

PMID- 11222211
TI  - Diffuse abnormalities of the trachea and main bronchi.

PMID- 11222212
TI  - Paclitaxel-induced hypersensitivity pneumonitis: radiographic and CT findings.

PMID- 11222213
TI  - Learning curve for stereotactic breast biopsy: how many cases are enough?
AB  - OBJECTIVE: The objective of this study was to evaluate the learning curve for
      stereotactic breast biopsy. MATERIALS AND METHODS: Retrospective review was
      performed of 923 consecutive lesions that underwent stereotactic breast biopsy
      performed by one of six radiologists. Four hundred fourteen lesions had 14-gauge
      automated core biopsy, and 509 subsequent lesions had vacuum-assisted biopsy (14
      gauge in 163 and 11-gauge in 346). Medical records were reviewed to determine the
      technical success rate and false-negative rate as a function of operator
      experience. RESULTS: For 14-gauge automated core biopsy, a significantly lower
      technical success rate was seen for the first five cases of each radiologist than
      for subsequent cases (25/30 = 83.3% versus 366/384 = 95.3%, p < 0.02) and for the
      first 20 cases than for subsequent cases (90/100 = 90% versus 284/296 = 95.9%, p
      < 0.05). For 11-gauge vacuum-assisted biopsy, a significantly lower technical
      success rate was seen for the first five cases than for subsequent cases (17/20 =
      85.0% versus 310/322 = 96.3%, p < 0.05) and for the first 15 cases than for
      subsequent cases (54/60 = 90.0% versus 273/283 = 96.5%, p = 0.03). The false
      negative rate was higher for the first 15 cases compared with subsequent cases
      both for stereotactic 14-gauge automated core biopsy (4/31 = 12.9% versus 3/115 =
      2.6%, p < 0.04) and for stereotactic 11-gauge vacuum-assisted biopsy (2/27 = 7.4%
      versus 0/85 = 0%, p < 0.06). CONCLUSION: A learning curve exists for stereotactic
      breast biopsy. Significantly higher technical success rates and lower false
      negative rates were observed after the first five to 20 cases for 14-gauge
      automated core biopsy and after the first five to 15 cases for 11-gauge vacuum
      assisted biopsy. Even after a radiologist has experience with stereotactic
      biopsy, changes in equipment may result in a new learning curve.

PMID- 11222215
TI  - Is a pseudocystic serpentine mass a sonographic indicator of breast lymphoma?
      Radiologic-histologic correlation of an unusual finding.

PMID- 11222214
TI  - Medical audit of diagnostic mammography examinations: comparison with screening
      outcomes obtained concurrently.
AB  - OBJECTIVE: We performed a medical audit of our diagnostic mammography practice
      and compared clinical outcomes with those of screening mammography examinations
      performed concurrently. MATERIALS AND METHODS: We analyzed 46,857 consecutive
      mammography examinations (10,007 diagnostic, 36,850 screening) from 1997 to 2000,
      including data on demographics, image interpretation, and biopsy (including size,
      nodal status, and cancer stage). RESULTS: The mean age at diagnostic mammography
      was 55.8 years (mean age at screening mammogram, 59.1 years; p < 0.0001). Among
      patients who underwent diagnostic examinations, 14.7% had a strong or very strong
      family history of breast cancer (screening, 11.6%; p < 0.0001). Examination
      findings were interpreted as abnormal in 14.4% (screening, 5.2%; p < 0.0001).
      Biopsy was performed in 11.9% (screening, 1.4%; p < 0.0001). Forty-six percent of
      the biopsies were positive for malignancy (screening, 38%; p < 0.0001). The
      cancer detection rate was 55 per 1000 (screening, 5/1000; p < 0.0001). Of cancers
      found, 74.4% were stage 0 or I (screening, 89.3%; p < 0.0001), average size was
      18.0 mm (screening, 12.9 mm; p < 0.0001), and axillary nodes were positive for
      malignancy in 19.9% of invasive cancers (screening, 6.3; p < 0.0001). Differences
      between diagnostic and screening outcomes were attributable predominantly to the
      subgroup of diagnostic examinations performed for evaluation of palpable masses.
      CONCLUSION: Medical auditing of diagnostic mammography examinations yields
      substantially different results compared with those of screening examinations,
      including different patient demographics; higher number of positive biopsies;
      higher cancer detection rates; and larger, more advanced-stage cancers.
      Diagnostic and screening data should be segregated during auditing, or if this is
      not possible, analysis of combined results should be based on known differences
      between diagnostic and screening outcomes.

PMID- 11222216
TI  - Serial MR imaging of pineal cysts: implications for natural history and follow
      up.
AB  - OBJECTIVE: The purpose of this study was to examine the frequency of change in
      size of pineal cysts on serial MR studies. MATERIALS AND METHODS: Thirty-two
      patients (19 females, 13 males) with a diagnosis of pineal cyst at any time who
      underwent brain MR imaging more than once in a period of at least 6 months were
      identified by computerized search of radiology reports. Four patients underwent
      MR imaging to follow up pineal cysts, whereas the remaining patients were imaged
      for a variety of indications, including intracerebral neoplasms. Measurements of
      maximal cyst dimension on both initial and latest follow-up studies were obtained
      in all patients, and cyst volumes were calculated in 23 patients. RESULTS: Length
      of follow-up ranged from 6 months to 9 years. All cysts were considered
      incidental and none were treated. Maximal cyst dimensions ranged from 0.5 to 2.2
      cm. On average, there was no significant change in cyst volume. The maximal
      dimension of the cyst did not change in 24 (75%) of 32 patients. Two cysts
      resolved completely on follow-up, three cysts decreased by 2-4 mm, two cysts
      enlarged by 2-3 mm, and one cyst formed and grew to 1.2 cm. CONCLUSION: Whereas
      the size of pineal cysts as a whole remained unchanged on serial MR studies,
      cysts may either form or involute in individual patients. Small increases in cyst
      size did occur but were not associated with specific clinical findings. These
      findings suggest that typical pineal cysts may be followed up on a clinical basis
      alone rather than on imaging.

PMID- 11222217
TI  - Sonography of the cervical vagus nerve: normal appearance and abnormal findings.
AB  - OBJECTIVE: The purpose of this study was to assess the appearance of the cervical
      vagus nerve in healthy individuals and to investigate the potential role of
      sonography in revealing neck masses that cause vagal dysfunction. SUBJECTS AND
      METHODS: We examined 150 consecutive patients. In 144 patients the presence of
      thyroid, salivary gland, or lymph node disease was suspected. In three patients a
      cervical mass was palpable, and three patients had symptoms of dysfunction of the
      inferior laryngeal or vagal nerves. The pathologic diagnoses of the masses were
      obtained at biopsy. RESULTS: In 144 individuals the normal vagus nerve was
      recognized on each side of the neck as a thin band that occupied the posterior
      angle formed by the common carotid artery and the internal jugular vein. Three
      patients had tumors arising from the vagus nerve: one neurofibroma, one
      neurinoma, and one chemodectoma. These tumors were located in the neurovascular
      bundle and posterior to the vessels; their origin from the vagus nerve was
      clearly visible in all patients because of the contiguity of the mass with the
      nerve bundle. In the other three patients, sonography revealed an extrinsic mass
      that compressed and displaced the vagus nerve out of its longitudinal axis; two
      cases were hyperplastic nodules of the thyroid, and in one case the nodule was a
      branchial cyst. CONCLUSION: Sonography can reveal the vagus nerve in healthy
      conditions and correctly reveal the vagal origin of some tumors in the
      parapharyngeal spaces.

PMID- 11222219
TI  - Sonographic appearance of focal thyroiditis.
AB  - OBJECTIVE: The purpose of this study is to report the sonographic appearance of
      focal thyroid nodules that prove to be lymphocytic thyroiditis on fine-needle
      aspiration. CONCLUSION: In a patient population undergoing sonography for
      palpable nodular disease without known thyroiditis, focal nodules of thyroiditis
      had a wide variety of appearances. They most commonly appeared as solid
      hyperechoic nodules with ill-defined margins. However, the echogenicity was
      variable, and calcification and cystic-appearing regions were also noted. The
      vascularity of these nodules as assessed with color Doppler and power Doppler
      sonography also varied widely. Biopsy of these lesions is still necessary because
      there are no sonographic features that can reliably diagnose these lesions as
      thyroiditis and differentiate them from other lesions.

PMID- 11222220
TI  - Pulmonary metastases at diagnosis of neuroblastoma in pediatric patients: CT
      findings and prognosis.
AB  - OBJECTIVE: We undertook this study to determine the frequency, CT appearance, and
      clinical implications of the rare occurrence of pulmonary metastases among
      children presenting with neuroblastoma. MATERIALS AND METHODS: A search of the
      Children's Cancer Group database revealed 21 of 567 children with reported lung
      metastases at original diagnosis of neuroblastoma. CT examinations available for
      17 of these patients were analyzed retrospectively to determine if lung
      metastases were present, and if so, to characterize their radiographic features.
      RESULTS: Seventeen (3%) of 567 patients presenting with Evans stage IV
      neuroblastoma had confirmed pulmonary metastases at diagnosis. All had metastases
      to at least one site other than the lungs. The most common CT appearance of
      pulmonary lesions was of up to five, small, bilateral, noncalcified nodules. In
      nine patients (53%), the pulmonary nodules initially resolved with treatment. In
      this cohort, six children developed progressive disease and died, and three are
      still alive. All eight children whose lung lesion did not completely respond to
      treatment died. Overall, children with pulmonary metastases had unfavorable
      Shimada histology, a higher association with amplification of the MYCN oncogene
      (p = 0.0002), and a decreased event-free survival (p < 0.001) when compared with
      all children with stage IV neuroblastoma without pulmonary metastases.
      CONCLUSION: The search for neuroblastoma lung metastases, which occur more
      frequently than previously reported, is clinically important because their
      presence portends a poor prognosis.

PMID- 11222221
TI  - Percutaneous transhepatic cholangiography and biliary drainage in pediatric liver
      transplant patients.
AB  - OBJECTIVE: In children with liver transplants, percutaneous transhepatic
      cholangiography has a critical role in evaluation and treatment of biliary
      complications. The purpose of this study was to evaluate the technical success
      and complication rates of percutaneous transhepatic cholangiography and biliary
      drain placement in children who underwent liver transplantation. MATERIALS AND
      METHODS: Between January 1, 1995 and July 1, 1999, 120 pediatric percutaneous
      transhepatic cholangiography procedures were performed in 76 patients (34 boys,
      42 girls; age range, 5 months to 18 years; mean age, 5.3 years). Patients had
      received left lateral segment, whole-liver, or split-liver transplant grafts.
      Retrospective review of all pertinent radiology studies and electronic chart
      review were performed. RESULTS: A diagnostic cholangiogram was obtained in 96%
      (115/120) of all procedures and drainage catheter placement was successful in 89%
      (88/99) of attempts. In patients with nondilated intrahepatic bile ducts, a
      diagnostic cholangiogram was obtained in 92% (46/50) of procedures, and drainage
      catheter placement was successful in 76% (19/25) of attempts. Minor complications
      occurred in 10.8% (13/120) of procedures and included transient hemobilia with
      mild drop in hematocrit level (n = 2), mild pancreatitis (n = 1), fever with
      bacteremia (n = 5), and fever with negative blood cultures (n = 5). Major
      complications occurred in 1.7% (2/120) of procedures and included sepsis (n = 1)
      and hemoperitoneum requiring immediate surgery (n = 1). CONCLUSION: Percutaneous
      transhepatic cholangiography and biliary drainage can be performed with high
      technical success and low complication rates in pediatric liver transplant
      patients, even in those with nondilated intrahepatic ducts.

PMID- 11222222
TI  - Radiologic removal of buried gastrostomy bumpers in pediatric patients.

PMID- 11222223
TI  - Cervical laminar torus fracture in a child.

PMID- 11222224
TI  - Lesions of the menisci of the knee: value of MR imaging criteria for recognition
      of unstable lesions.
AB  - OBJECTIVE: This study aimed to determine the value of four MR imaging criteria
      for evaluating unstable meniscal lesions. MATERIALS AND METHODS: Criteria for
      unstable meniscal lesions were the presence of a displaced meniscal fragment,
      visibility on more than three 3-mm-thick coronal and two 4-mm-thick sagittal
      images, having more than one orientation plane or more than one pattern (contour
      irregularity, peripheral separation, tear), and having intrameniscal high signal
      intensity on T2-weighted spin-echo images. Sensitivity, specificity, and positive
      and negative predictive values for recognition of instability among all meniscal
      lesions were determined for the presence of each individual criterion and for the
      presence of at least one criterion in 50 consecutive patients (mean age, 46
      years) who underwent MR imaging and subsequent arthroscopy. RESULTS:
      Sensitivities and specificities of these four criteria ranged between 18% and 54%
      and between 94% and 100%, respectively. Positive and negative predictive values
      ranged between 92% and 100% and between 39% and 52%, respectively. The presence
      of at least one criterion enabled recognition of unstable lesions with a
      sensitivity and specificity of 82% and with positive and negative predictive
      values of 90% and 70%, respectively. CONCLUSION: The four MR imaging criteria
      have high specificities and positive predictive values and low sensitivities and
      negative predictive values when evaluating unstable meniscal lesions.

PMID- 11222225
TI  - Sonographic examination of lateral epicondylitis.
AB  - OBJECTIVE: The purpose of this study was to describe the sonographic appearance
      of the common extensor origin in cadavers and asymptomatic volunteers, and to
      relate this appearance to the findings in patients with lateral epicondylitis.
      SUBJECTS AND METHODS: Seventy-two elbows in 71 patients with lateral
      epicondylitis were examined on sonography. Most of the patients (60/71) gave a
      history of repetitive microtrauma. The injuries were evaluated with respect to
      location and severity. Focal areas of degeneration, discrete cleavage tears, and
      involvement of the lateral collateral ligament were identified. Calcification and
      bony changes were noted. The appearance of the normal common extensor tendon was
      described, and cadaveric specimens were dissected. Twenty-one patients
      subsequently underwent surgery. RESULTS: The normal common extensor origin is
      composed of longitudinal fibrils bound closely with the extensor carpi radialis
      brevis constituting most of the deep fibers, with the extensor digitorum making
      up the superficial part. The lateral collateral ligament can be identified as a
      discrete and separate band. The most common appearance of lateral epicondylitis
      is a focal hypoechoic area in the deep part of the tendon (46/72). These focal
      areas were identified at surgery and corresponded histologically to collagen
      degeneration with fibroblastic proliferation. Often discrete cleavage planes
      traversing the tendon were manifest as partial (18/72) and complete (2/72) tears.
      The lateral collateral ligament was involved in eight of 72 elbows. CONCLUSION:
      Sonography of the common extensor origin can be used to confirm lateral
      epicondylitis in patients with lateral elbow pain and provide information about
      the severity of the disease.

PMID- 11222226
TI  - Imaging findings in pseudocystic osteosarcoma.
AB  - OBJECTIVE: Our purpose was to describe four female patients with osteosarcoma
      whose clinical and imaging findings primarily suggested either simple or
      aneurysmal bone cyst. All lesions were osteolytic, intracompartmental, and
      expanded bone without periosteal reaction. None of the patients presented during
      the peak age incidence for osteosarcoma. From imaging to histologic diagnosis,
      the discovery of osteosarcoma ranged from 1 week to 3 years. CONCLUSION: Atypical
      osteosarcoma may rarely mimic simple or aneurysmal bone cyst radiologically and
      may show a nonmalignant rate of growth. It may be more frequently encountered in
      females and may not present during the peak age incidence for osteosarcoma.
      Microscopically, the tumors were not cystic, necrotic, or telangiectatic but were
      conventional osteosarcoma and osteoclast-rich osteosarcoma.

PMID- 11222227
TI  - Effect of vascular occlusion on radiofrequency ablation of the liver: results in
      a porcine model.
AB  - OBJECTIVE: This study determined the effect of vascular occlusion on
      radiofrequency lesion shape, volume, and temperature in a porcine liver model.
      SUBJECTS AND METHODS: Radiofrequency lesions (n = 33) were created in the livers
      of six domestic pigs in vivo using a multiprong radiofrequency electrode. Lesions
      were randomly assigned to one of four vascular occlusion groups: portal vein,
      hepatic artery, Pringle maneuver (both hepatic artery and portal vein), or no
      occlusion. Radiofrequency parameters were time, 7 min; power, 50 W; and target
      temperature, 100 degrees C. Temperatures were measured 5, 10, and 15 mm from the
      electrode. After the animals were sacrificed, the lesions were excised. Lesion
      volume, diameter, and shape; maximum temperature; and time exposed to lethal
      temperatures (42-60 degrees C) were determined. RESULTS: Lesion volume was
      greatest with the Pringle maneuver lesions (12.6 +/- 4.8 cm(3)), followed by
      occlusion of the portal vein (8.6 +/- 3.8 cm(3)), occlusion of the hepatic artery
      (7.6 +/- 2.9 cm(3)), and no occlusion (4.3 +/- 1.0 cm(3)) (p < 0.05). Maximum
      lesion diameter was similar with the Pringle maneuver (3.3 +/- 0.3 cm), the
      portal vein (3.3 +/- 0.2 cm), and the hepatic artery (3.2 +/- 0.2 cm) groups
      compared with no occlusion (2.6 +/- 1.0 cm) (p < 0.05). Minimum lesion diameter
      ranged from 2.9 cm for Pringle maneuver lesions to 1.0 cm for lesions with no
      occlusion (p < 0.05). Vascular occlusion increased the time tissue was exposed to
      lethal temperatures (> 42-60 degrees C) and created more spherical lesions than
      no occlusion. CONCLUSION: Vascular occlusion combined with radiofrequency
      ablation increases the volume of necrosis, creates a more spherical lesion, and
      increases the time tissue is exposed to lethal temperatures when compared with
      radiofrequency alone. Most of this vascular occlusion effect could be
      accomplished with hepatic artery occlusion alone.

PMID- 11222228
TI  - Successful resuscitative sacral artery embolization after traumatic unstable
      pelvic fracture.

PMID- 11222229
TI  - Multiple bile duct biopsies using a sheath with a side port: usefulness of
      intraductal sonography.
AB  - OBJECTIVE: We clarified the number of biopsies required to determine malignancy
      of the biliary tract on the basis of the type of bile duct tumor. SUBJECTS AND
      METHODS: Patients with a biliary tract malignancy (n = 33) and a benign biliary
      stenosis (n = 3) underwent biopsy via the percutaneous transhepatic route. We
      performed intraductal sonography using a 20-MHz probe with a 2.0-mm diameter. The
      sonographic findings were prospectively classified as polypoid, circular, or
      semicircular. The tip of a long 9-French sheath with a side port was wedged into
      the stenosis, and six specimens were obtained with a 1.8-mm-diameter forceps with
      serrated cups. RESULTS: When cholangiography or intraductal sonography showed a
      polypoid lesion, the sensitivity of two biopsies was 100% (6/6). When
      cholangiography showed a stenotic lesion, the sensitivity of nine biopsies (96%,
      26/27) was superior to that of two biopsies (74%, 20/27; p < 0.05). When
      intraductal sonography showed a circular lesion, the sensitivity of three
      biopsies (100%, 14/14) was superior to that of a single biopsy (64%, 9/14; p <
      0.05). When it showed a semicircular lesion, the sensitivity of nine biopsies
      (92%, 12/13) was superior to that of two biopsies (54%, 7/13; p < 0.05).
      CONCLUSION: Bile duct biopsy using a sheath with a side port has a high
      sensitivity. However, the number of biopsies required depends on the
      cholangioscopic and intraductal sonographic appearance of the tumor.

PMID- 11222230
TI  - Changes in wall mechanics after endovascular stenting in the rabbit aorta:
      comparison of three stent designs.
AB  - OBJECTIVE: The aim of this study was to evaluate changes in the wall mechanics of
      small-diameter arteries after endovascular placement of three different stents.
      SUBJECTS AND METHODS: Five self-expandable stents (Wallstent), five balloon
      expandable noncovered Palmaz stents, and three balloon-expandable covered stents
      (Jostent) were placed in the infrarenal aorta of 13 New Zealand white rabbits.
      Systolic blood pressure changes, blood-flow velocity, systolic diameter, and
      diameter changes were measured and used to calculate the diameter compliance, the
      distensibility coefficient, and the pulsatility index. RESULTS: Compliance (10(
      3) mm kPa(-1)) was 75.3 +/- 20.1 before stenting and reached 94.7 +/- 42.2
      upstream, 38.8 +/- 14.2 at the stent level (p < 0.05), and 70.8 +/- 23.2
      downstream from the stent. Distensibility (10(-3) kPa(-1)) was 24.3 +/- 6.3
      before stenting and reached 27.8 +/- 10.3 upstream, 10.5 +/- 4.4 at the stent
      level (p < 0.001), and 21.9 +/- 8.6 downstream from the stent. Compliance and
      distensibility were significantly lower at the stent level than upstream and
      downstream (p < 0.05). Aortic diameter increased significantly at the stent level
      from 3.11 +/- 0.40 mm before to 3.76 +/- 0.42 mm after stenting. No significant
      difference was found among the three stent designs for all the studied data.
      CONCLUSION: Regardless of the three tested stent designs, endovascular stenting
      produces a significant decrease in arterial wall compliance of the rabbit aorta.

PMID- 11222231
TI  - Percutaneous jejunostomy using CT fluoroscopy.

PMID- 11222232
TI  - American College of Radiology Appropriateness Criteria and Standards: separate
      programs.

PMID- 11222233
TI  - Additional foot radiographs.

PMID- 11222234
TI  - Imaging of the subcoracoid bursa.

PMID- 11222235
TI  - Physician sonography training competency.

PMID- 11222236
TI  - Percutaneous cholangiography and drainage in patients with nondilated
      intrahepatic bile ducts.

PMID- 11222237
TI  - Author's correction.

PMID- 11222238
TI  - Paget's disease causing an Arnold-Chiari Type 1 malformation: radiographic
      findings.

PMID- 11222239
TI  - Percutaneous microwave coagulation therapy using artificial ascites.

PMID- 11222240
TI  - Ectopic pregnancy showing interesting findings on MR imaging.

PMID- 11222241
TI  - Floral development in Aphandra (Arecaceae).
AB  - The organogenesis of staminate flower clusters and flowers and some observations
      on the corresponding pistillate structures of Aphandra natalia are described and
      compared with those of the other two genera in the Phytelephantoideae
      (Arecaceae). In Aphandra, staminate flowers are borne in monopodial clusters of
      mostly four (1-6) flowers. Each flower is surrounded by two pairs of subopposite
      bracteoles and has two rather indistinctly four-parted whorls of perianth parts.
      Stamen primordia arise on a shallow apical dome and then centrifugally down the
      sides of a long, angled, and laterally flattened receptacle. Immediately before
      the staminate bud opens, the floral receptacle below the androecium rapidly
      elongates, becoming funnel-shaped, with the bracteoles and a perianth sheath
      adnate to it forming a pseudopedicel. Epidermal and subepidermal layers of these
      pseudopedicels split at anthesis and release a great number of raphide idioblasts
      that resemble the pollen grains in shape and size. It is hypothesized that the
      idioblasts deter pollen feeding or ovidepositing insects. The phylogenetic
      implications of these findings are important within the Phytelephantoideae and
      among palms in general.

PMID- 11222242
TI  - Structural homology and developmental transformations associated with ovary
      diversification in Lithophragma (Saxifragaceae).
AB  - Lithophragma, comprising only ten species, encompasses a remarkable diversity of
      ovary positions, reported to range from inferior to superior. The structural
      homology of the gynoecium and developmental transformations associated with ovary
      diversification are investigated for Lithophragma. Scanning electron and light
      microscopy indicate that all species of Lithophragma have epigynous flowers.
      Lithophragma campanulatum, L. glabrum, and L. heterophyllum have ovaries that
      externally appear nearly superior, but are actually shallowly inferior or
      "pseudosuperior." The inferior ovaries of Lithophragma species can be
      conceptually divided into superior and inferior regions that meet at the point of
      perianth and androecial insertion. Static and ontogenetic allometry reveal that
      across the species of Lithophragma the lengths of these two ovary regions are
      coordinated. Ovary regions in mature flowers display an approximately linear
      relationship that can be expressed through the allometric equation SL = -0.5314
      IL + 2.0348 (where SL and IL are the lengths of the superior and inferior regions
      of the ovary, respectively; r = 0.7683, df = 35, P = 2.45 * 10). Mapping
      ontogenetic allometries onto a recent phylogeny for Lithophragma shows that ovary
      position evolution is bidirectional and has shifted toward greater superiority in
      some species and greater inferiority in others.

PMID- 11222243
TI  - Seasonal conductivity and embolism in the roots and stems of two clonal ring
      porous trees, Sassafras albidum (Lauraceae) and Rhus typhina (Anacardiaceae).
AB  - Seasonal xylem (wood) conductivity and embolism (air blockage) patterns were
      monitored in roots vs. stems of two clonal ring-porous tree species, Sassafras
      albidum and Rhus typhina, throughout 1996 and 1997. Stems of both species were
      100% embolized in the early spring and became conductive by late June following
      leaf expansion and maturation of new earlywood vessels. Dyes indicated the stem
      conduction was restricted almost exclusively to the current year's growth ring.
      Stems became totally embolized again by early October, before the first freezing
      temperatures. In contrast, woody roots of both species maintained low embolism
      values, many conductive growth rings, and high conductivity values regardless of
      the season. No positive root pressures were detected in either species. The mean
      frost depth (204 +/- 11 mm) was deeper than all sampled roots of Rhus and 47% of
      sampled roots of Sassafras. The roots that had been in frozen soil either avoided
      embolism altogether or they were able to reverse embolism by a mechanism other
      than positive root pressures.

PMID- 11222244
TI  - Tests of pre- and postpollination barriers to hybridization between sympatric
      species of Ipomopsis (Polemoniaceae).
AB  - The Ipomopsis aggregata species complex (Polemoniaceae) includes species pairs
      that hybridize readily in nature as well as pairs that meet along contact zones
      with no apparent hybridization. Artificial hybrids can be made between I.
      aggregata and I. arizonica, yet morphological intermediates between these two
      species have not been observed in natural populations. This apparent lack of
      hybridization is perplexing given that plants of the two species often grow
      within a few metres of each other and both species have red flowers visited by
      the same species of hummingbirds. We used trained hummingbirds to examine pollen
      transfer within and between species. We also hand-pollinated flowers to examine
      paternal success of heterospecific and conspecific pollen, testing paternity with
      electrophoretic examination of seeds. Hummingbirds were not simply better at
      transferring pollen within than between species. Instead, I. arizonica was a
      better pollen donor so that considerable pollen transfer was observed from I.
      arizonica to I. aggregata, but very little in the opposite direction. Conversely,
      once pollen arrived at stigmas, I. arizonica pollen performed very poorly on I.
      aggregata pistils. However, pollen from I. aggregata could, in some cases, sire
      seeds on I. arizonica. We hypothesize that hybrids are scarce in nature, in part,
      because of asymmetric barriers to reproduction: little pollen transfer in one
      direction and poor pollen performance in the other.

PMID- 11222245
TI  - Breeding System and pollination of selected plants endemic to Juan Fernandez
      Islands.
AB  - We conducted field studies on the Juan Fernandez Islands flora on the breeding
      system of 25 endemic species from 17 families. We recorded data on flower
      features, pollen and ovule number, pollen/ovule ratio, pollen size, self
      compatibility, floral visitors, and pollination. Flowers are mostly
      hermaphrodite, inconspicuous, small, and green. Six species are dioecious. Over
      80% of the cosexual species are self compatible. However, many species are
      dichogamous (mostly protandrous); thus, even the self-compatible species may
      require pollen transfer. Selfing through geitonogamy seems to be the most common
      system, and several species express mixed breeding systems. Floral visitors are
      uncommon to rare, except for two hummingbird species (one native and one endemic)
      that visit five species we studied. In more than 300 h of observation of flowers
      over three field seasons, we detected only 23 native insect visits representing
      ten species (Diptera, Lepidoptera, and Coleoptera). One species each of an
      introduced ant and an introduced bee were also observed on some flowers, all near
      the single human settlement of San Juan Bautista. Wind directly moving pollen, or
      indirectly via shaking the flowers, is the most important pollen distribution
      mechanism. The majority of the wind-pollinated species bear some typical
      anemophilous features, but also others not characteristic of wind pollination,
      that presumably represent the condition of their biotically pollinated ancestors.
      Floral features often reflect ancestral reproductive systems, so floral biology
      studies of oceanic islands in particular must be done with cognizance of presumed
      ancestral forms, because the observed characters can be misleading.

PMID- 11222246
TI  - Ecological benefits of myrmecochory for the endangered chaparral shrub
      Fremontodendron decumbens (Sterculiaceae).
AB  - Fremontodendron decumbens grows in a single county in central California, USA.
      Prior research showed that its elaiosome-bearing seeds are dispersed by the
      harvester ant Messor andrei. I tested several hypotheses regarding the positive
      role of ant-mediated dispersal to F. decumbens: (1) Does ant-mediated seed
      dispersal facilitate seed escape from rodent predation?; (2) Does ant processing
      of seeds stimulate germination?; (3) Are ant middens more suitable microsites for
      seed or seedling survival in unburned chaparral areas?; and (4) Do survival
      benefits of dispersal occur post-fire in the form of differences in seedling
      survival probabilities and, if so, why? Results of tests of each hypothesis were:
      (1) similar percentages of seeds placed on ant middens and under F. decumbens
      shrub canopies were destroyed by rodents, but seeds from which elaiosomes had
      been removed were more likely to escape rodent predation; (2) seeds processed by
      ants did not germinate more readily than seeds removed directly from shrub
      branches; (3) seedling predation was a major cause of mortality in unburned
      chaparral on both ant middens and under shrubs, and overall seedling survival did
      not differ between the two microsites; (4) post-burn seedling survival was
      significantly greater for seedlings dispersed away from F. decumbens shrub
      canopies, because dispersed seedlings were both less likely to be killed by
      predators and more likely to be growing in a gap created by the fire-caused death
      of an established shrub. I concluded that the major ecological benefit to F.
      decumbens of ant-mediated seed dispersal was elevated post-fire seedling survival
      resulting from enhanced escape by dispersed seedlings from both predation and
      competition.

PMID- 11222247
TI  - Mechanisms of differential pollen donor performance in wild radish, Raphanus
      sativus (Brassicaceae).
AB  - In order to understand the characters on which sexual selection might operate in
      plants, it is critical to assess the mechanisms by which pollen competition and
      mate choice occur. To address this issue we measured a number of postpollination
      characters, ranging from pollen germination and pollen tube growth to final seed
      paternity, in wild radish. Crosses were performed using four pollen donors on a
      total of 16 maternal plants (four each from four families). Maternal plants were
      grown under two watering treatments to evaluate the effects of maternal tissue on
      the process of mating. The four pollen donors differed significantly in number of
      seeds sired and differed overall in the mating characters measured. However, it
      was difficult to associate particular mechanistic characters with ability to sire
      seeds, perhaps because of interactions among pollen donors within styles or among
      pollen donors and maternal plants. The process of pollen tube growth and
      fertilization differed substantially among maternal watering treatments, with
      many early events occurring more quickly in stressed plants. Seed paternity,
      however, was somewhat more even among pollen donors used on stressed maternal
      plants, suggesting that when maternal tissue is more competent, mating is slowed
      and is more selective.

PMID- 11222248
TI  - Nonlocal transplantation and outbreeding depression in the subshrub Lotus
      scoparius (Fabaceae).
AB  - The genetic background of transplants used to create or augment wild populations
      may affect the long-term success of restored populations. If seed sources are
      from differently adapted populations, then the relative performance of progeny
      from crosses among populations may decrease with an increase in genetic
      differences of parents and in the differences of parental environments to the
      transplant location. We evaluated the potential for such outbreeding depression
      by hybridizing individuals from six different populations of Lotus scoparius var.
      scoparius and L. s. var. brevialatus. We used allozyme data to calculate genetic
      distances between source populations, and compiled climatic data and measured
      soil traits to estimate environmental distances between source populations. We
      found significant outbreeding depression following controlled crosses. In the
      greenhouse, the success of crosses (seeds/flower * seedlings/seed) decreased with
      increasing genetic distance between populations revealing genetically based
      outbreeding depression unrelated to local adaptation. After outplanting to one
      native site (in situ common garden), field cumulative fitness of progeny
      (survival * fruit production) decreased significantly with mean environmental
      distance of the parental populations to the transplant site, but not with genetic
      distance between the crossed populations. This result is consistent with a
      disruption of local adaptation. At the second, ecologically contrasting common
      garden, where low survival reduced statistical power, field cumulative fitness
      (survival * progeny height) did not decrease significantly with either
      environmental distance or genetic distance. Overall, intervariety crosses were 40
      and 50% as fit (seeds/flower * seedlings/seed * survival * fruits at the first
      garden or * height at the second) as intravariety crosses. These results suggest
      that the cumulative outbreeding depression was caused by a combination of
      genetically based ecological differences among populations and other genomic
      coadaptation. We conclude that mixing genetically differentiated seed sources of
      Lotus scoparius may significantly lower the fitness of augmented or restored
      populations. Genetic and environmental similarities of source populations
      relative to the transplant site should be considered when choosing source
      materials, a practice recommended by recent seed transfer policies. Geographic
      separation was not a good surrogate for either of these measures.

PMID- 11222249
TI  - Transgressive character expression in a hybrid sunflower species.
AB  - Diploid hybrid lineages often are ecologically distinct from their parental
      species. However, it is unclear whether this niche divergence is typically
      achieved via hybrid intermediacy, a mixture of parental traits, and/or the
      evolution of extreme (transgressive) morphological and ecophysiological features.
      Here we compare an extensively studied hybrid sunflower species, Helianthus
      anomalus, with its putative parents, H. annuus and H. petiolaris, for 41
      morphological and 12 ecophysiological traits. Helianthus anomalus was
      morphologically intermediate for one trait (2.4%), parental-like for 23 traits
      (56.1%), and transgressive for 17 traits (41.5%). For ecophysiological traits, H.
      anomalus was not significantly different from one or both parents for nine traits
      (75%), and was transgressive for the remaining three (25%). Thus, H. anomalus
      appears to be a mosaic of parental-like and transgressive phenotypes. Although
      the fitness effects of the transgressive characters are not yet known, many of
      these characters are consistent with adaptations reported for other sand dune
      plants. Genetic studies are currently underway to ascertain whether these extreme
      characters arose as a direct byproduct of hybridization or whether they evolved
      via mutational divergence.

PMID- 11222250
TI  - Estimating near-infrared leaf reflectance from leaf structural characteristics.
AB  - The relationship between near-infrared reflectance at 800 nm (NIRR) from leaves
      and characteristics of leaf structure known to affect photosynthesis was
      investigated in 48 species of alpine angiosperms. This wavelength was selected to
      discriminate the effects of leaf structure vs. chemical or water content on leaf
      reflectance. A quantitative model was first constructed correlating NIRR with
      leaf structural characteristics for six species, and then validated using all 48
      species. Among the structural characteristics tested in the reflectance model
      were leaf trichome density, the presence or absence of both leaf bicoloration and
      a thick leaf cuticle (>1 MUm), leaf thickness, the ratio of palisade mesophyll to
      spongy mesophyll thickness (PM/SM), the proportion of the mesophyll occupied by
      intercellular air spaces (%IAS), and the ratio of mesophyll cell surface area
      exposed to IAS (A(mes)) per unit leaf surface area (A), or A(mes)/A. Multiple
      regression analysis showed that measured NIRR was highly correlated with
      A(mes)/A, leaf bicoloration, and the presence of a thick leaf cuticle (r = 0.93).
      In contrast, correlations between NIRR and leaf trichome density, leaf thickness,
      the PM/SM ratio, or %IAS were relatively weak (r < 0.25). A model incorporating
      A(mes)/A, leaf bicoloration, and cuticle thickness predicted NIRR accurately for
      48 species (r = 0.43; P < 0.01) and may be useful for linking remotely sensed
      data to plant structure and function.

PMID- 11222251
TI  - Barriers to interbreeding in the Eriophyllum lanatum (Asteraceae, Helenieae)
      species complex.
AB  - Sampling 426 plants from 271 populations of Eriophyllum lanatum, a western North
      American species complex, revealed 195 diploid (x = 8), 61 tetraploid, ten
      hexaploid, and five octoploid populations. Polyploids were ~400% more frequent in
      taxonomic intermediates. One to four supernumerary chromosomes were found in 13%
      of the populations. Artificial hybridizations were made in 58 of the 65 possible
      diploid-level combinations involving the ten varieties of E. lanatum and E.
      confertiflorum var. confertiflorum. Aberrations, mostly failure to pair normally,
      were observed in diakinesis or M(1) cells of progeny in 23 of 99 crosses. Studies
      of pollen stainability in cotton blue-lactophenol and other fertility indicators
      in 886 F(1)'s from 191 crosses involving 81 populations showed that strong (22
      40% pollen stainability) to weak (60-76% pollen stainability) barriers to
      interbreeding existed among diploids of the E. lanatum varieties and among them
      and E. confertiflorum var. confertiflorum. Pollen stainability was much higher in
      progenies of tetraploid, hexaploid, and octoploid intra- and interspecific
      crosses involving E. confertiflorum var. tanacetiflorum, E. jepsonii, and E.
      latilobum than in diploid ones, supporting the hypothesis that polyploidy has
      mainly served to stabilize the products of intervarietal and interspecific
      hybridizations.

PMID- 11222252
TI  - Phylogeny of the Celastraceae inferred from phytochrome B gene sequence and
      morphology.
AB  - Phylogenetic relationships within Celastraceae were inferred using a simultaneous
      analysis of 61 morphological characters and 1123 base pairs of phytochrome B exon
      1 from the nuclear genome. No gaps were inferred, and the gene tree topology
      suggests that the primers were specific to a single locus that did not duplicate
      among the lineages sampled. This region of phytochrome B was most useful for
      examining relationships among closely related genera. Fifty-one species from 38
      genera of Celastraceae were sampled. The Celastraceae sensu lato (including
      Hippocrateaceae) were resolved as a monophyletic group. Loesener's subfamilies
      and tribes of Celastraceae were not supported. The Hippocrateaceae were resolved
      as a monophyletic group nested within a paraphyletic Celastraceae sensu stricto.
      Goupia was resolved as more closely related to Euphorbiaceae, Corynocarpaceae,
      and Linaceae than to Celastraceae. Plagiopteron (Flacourtiaceae) was resolved as
      the sister group of Hippocrateoideae. Brexia (Brexiaceae) was resolved as closely
      related to Elaeodendron and Pleurostylia. Canotia was resolved as the sister
      group of Acanthothamnus within Celastraceae. Perrottetia and Mortonia were
      resolved as the sister group of the rest of the Celastraceae. Siphonodon was
      resolved as a derived member of Celastraceae. Maytenus was resolved as three
      disparate groups, suggesting that this large genus needs to be recircumscribed.

PMID- 11222253
TI  - Phylogenetic relationships of Loasaceae subfamily Gronovioideae inferred from
      matK and ITS sequence data.
AB  - Members of subfamily Gronovioideae are distinctive among Loasaceae in their
      androecial and gynoecial simplicity. The four genera of the subfamily differ,
      however, in chromosome number, floral novelties, and pollen exine sculpturing,
      which led to suggestions that the Gronovioideae were polyphyletic. Phylogenetic
      analyses based on sequences of the chloroplast gene matK and the internal
      transcribed spacer region (ITS) of nuclear rDNA have been conducted using
      parsimony and maximum likelihood methods to assess the monophyly of Gronovioideae
      and to determine the sister group relationships of gronovioid genera. The results
      show Gronovioideae are monophyletic and placed as the sister to Mentzelia. Within
      Gronovioideae, Petalonyx is sister to a clade consisting of Cevallia, Gronovia,
      and Fuertesia. Among the remaining Loasaceae, subfamily Mentzelioideae, as
      originally circumscribed, is paraphyletic. Subfamily Loasoideae is placed as the
      sister to the Gronovioideae-Mentzelia clade.

PMID- 11222254
TI  - Molecular markers reveal little genetic differentiation among Aconitum
      noveboracense and A. columbianum (Ranunculaceae) populations.
AB  - Aconitum noveboracense, a rare, herbaceous perennial, is restricted to recently
      unglaciated areas in Iowa, Wisconsin, Ohio, and New York, and federally
      classified as a threatened species. These populations may be disjuncts of the
      common congener, A. columbianum Nutt., which occurs in the mountains of the
      western United States. Morphological characters do not reliably separate these
      taxa. The identity of Black Hills populations, located between the ranges of the
      rare and common species, is also uncertain. We characterized genetic variation
      within and among the Aconitum populations in question using isozymes and randomly
      amplified polymorphic DNA (RAPDs). Isozymes indicate a high degree of similarity
      among all populations and a high level of genetic diversity in Black Hills
      populations. Of 97 scorable RAPD loci, 89.7% are polymorphic and clearly resolve
      most populations. Like isozymes, RAPDs indicate high levels of genetic diversity
      in the Black Hills and very strong similarity of these populations to A.
      columbianum from the Bighorn Mountains. Aconitum noveboracense populations show
      >80% similarity to A. columbianum populations. A population of A. uncinatum from
      Ohio shows the greatest differentiation from other populations. Therefore, both
      isozyme and RAPD data concur with the recent treatment of A. noveboracense and A.
      columbianum as a single species.

PMID- 11222255
TI  - Disintegration of the scrophulariaceae.
AB  - A molecular systematic study of Scrophulariaceae sensu lato using DNA sequences
      of three plastid genes (rbcL, ndhF, and rps2) revealed at least five distinct
      monophyletic groups. Thirty-nine genera representing 24 tribes of the
      Scrophulariaceae s.l. (sensu lato) were analyzed along with representatives of 15
      other families of Lamiales. The Scrophulariaceae s.s. (sensu stricto) include
      part or all of tribes Aptosimeae, Hemimerideae, Leucophylleae, Manuleae,
      Selagineae, and Verbasceae (= Scrophularieae) and the conventional families
      Buddlejaceae and Myoporaceae. Veronicaceae includes all or part of tribes
      Angelonieae, Antirrhineae, Cheloneae, Digitaleae, and Gratioleae and the
      conventional families Callitrichaceae, Globulariaceae, Hippuridaceae, and
      Plantaginaceae. The Orobanchaceae include tribes Buchnereae, Rhinantheae, and the
      conventional Orobanchaceae. All sampled members of Orobanchaceae are parasitic,
      except Lindenbergia, which is sister to the rest of the family. Family
      Calceolariaceae Olmstead is newly erected herein to recognize the phylogenetic
      distinctiveness of tribe Calceolarieae. The Calceolariaceae are close to the base
      of the Lamiales. The Stilbaceae are expanded by the inclusion of Halleria.
      Mimulus does not belong in any of these five groups.

PMID- 11222257
TI  - Registration of the expression patterns of Drosophila segmentation genes by two
      independent methods.
AB  - MOTIVATION: To construct an integrated map of Drosophila segmentation gene
      expression from partial data taken from individual embryos. RESULTS: Spline and
      wavelet based registration techniques were developed to register Drosophila
      segmentation gene expression data. As ground control points for registration we
      used the locations of extrema on gene expression patterns, represented in 1D. The
      registration method was characterized by unprecedented high accuracy. A method
      for constructing the integrated pattern of gene expression at cellular resolution
      was designed. These patterns were constructed for 9 segmentation genes belonging
      to gap and pair-rule classes.

PMID- 11222258
TI  - Pro-Frame: similarity-based gene recognition in eukaryotic DNA sequences with
      errors.
AB  - Performance of existing algorithms for similarity-based gene recognition in
      eukaryotes drops when the genomic DNA has been sequenced with errors. A
      modification of the spliced alignment algorithm allows for gene recognition in
      sequences with errors, in particular frameshifts. It tolerates up to 5% of
      sequencing errors without considerable drop of prediction reliability when a
      sufficiently close homologous protein is available (normalized evolutionary
      distance similarity score 50% or higher).

PMID- 11222259
TI  - PAQ: Partition Analysis of Quasispecies.
AB  - MOTIVATION: The complexities of genetic data may not be accurately described by
      any single analytical tool. Phylogenetic analysis is often used to study the
      genetic relationship among different sequences. Evolutionary models and
      assumptions are invoked to reconstruct trees that describe the phylogenetic
      relationship among sequences. Genetic databases are rapidly accumulating large
      amounts of sequences. Newly acquired sequences, which have not yet been
      characterized, may require preliminary genetic exploration in order to build
      models describing the evolutionary relationship among sequences. There are
      clustering techniques that rely less on models of evolution, and thus may provide
      nice exploratory tools for identifying genetic similarities. Some of the more
      commonly used clustering methods perform better when data can be grouped into
      mutually exclusive groups. Genetic data from viral quasispecies, which consist of
      closely related variants that differ by small changes, however, may best be
      partitioned by overlapping groups. RESULTS: We have developed an intuitive
      exploratory program, Partition Analysis of Quasispecies (PAQ), which utilizes a
      non-hierarchical technique to partition sequences that are genetically similar.
      PAQ was used to analyze a data set of human immunodeficiency virus type 1 (HIV-1)
      envelope sequences isolated from different regions of the brain and another data
      set consisting of the equine infectious anemia virus (EIAV) regulatory gene rev.
      Analysis of the HIV-1 data set by PAQ was consistent with phylogenetic analysis
      of the same data, and the EIAV rev variants were partitioned into two overlapping
      groups. PAQ provides an additional tool which can be used to glean information
      from genetic data and can be used in conjunction with other tools to study
      genetic similarities and genetic evolution of viral quasispecies.

PMID- 11222260
TI  - Variations on probabilistic suffix trees: statistical modeling and prediction of
      protein families.
AB  - MOTIVATION: We present a method for modeling protein families by means of
      probabilistic suffix trees (PSTs). The method is based on identifying significant
      patterns in a set of related protein sequences. The patterns can be of arbitrary
      length, and the input sequences do not need to be aligned, nor is delineation of
      domain boundaries required. The method is automatic, and can be applied, without
      assuming any preliminary biological information, with surprising success. Basic
      biological considerations such as amino acid background probabilities, and amino
      acids substitution probabilities can be incorporated to improve performance.
      RESULTS: The PST can serve as a predictive tool for protein sequence
      classification, and for detecting conserved patterns (possibly functionally or
      structurally important) within protein sequences. The method was tested on the
      Pfam database of protein families with more than satisfactory performance.
      Exhaustive evaluations show that the PST model detects much more related
      sequences than pairwise methods such as Gapped-BLAST, and is almost as sensitive
      as a hidden Markov model that is trained from a multiple alignment of the input
      sequences, while being much faster.

PMID- 11222261
TI  - Functional and structural genomics using PEDANT.
AB  - MOTIVATION: Enormous demand for fast and accurate analysis of biological
      sequences is fuelled by the pace of genome analysis efforts. There is also an
      acute need in reliable up-to-date genomic databases integrating both functional
      and structural information. Here we describe the current status of the PEDANT
      software system for high-throughput analysis of large biological sequence sets
      and the genome analysis server associated with it. RESULTS: The principal
      features of PEDANT are: (i) completely automatic processing of data using a wide
      range of bioinformatics methods, (ii) manual refinement of annotation, (iii)
      automatic and manual assignment of gene products to a number of functional and
      structural categories, (iv) extensive hyperlinked protein reports, and (v)
      advanced DNA and protein viewers. The system is easily extensible and allows to
      include custom methods, databases, and categories with minimal or no programming
      effort. PEDANT is actively used as a collaborative environment to support several
      on-going genome sequencing projects. The main purpose of the PEDANT genome
      database is to quickly disseminate well-organized information on completely
      sequenced and unfinished genomes. It currently includes 80 genomic sequences and
      in many cases serves as the only source of exhaustive information on a given
      genome. The database also acts as a vehicle for a number of research projects in
      bioinformatics. Using SQL queries, it is possible to correlate a large variety of
      pre-computed properties of gene products encoded in complete genomes with each
      other and compare them with data sets of special scientific interest. In
      particular, the availability of structural predictions for over 300 000 genomic
      proteins makes PEDANT the most extensive structural genomics resource available
      on the web.

PMID- 11222262
TI  - Alignment of 3D structures of macromolecular assemblies.
AB  - MOTIVATION: A number of macromolecular assemblies are being reconstructed in 3D
      from electron micrographs. The analysis yields a 3D matrix representing the
      protein density map. In reconstruction processes and in comparing the results of
      different experiments, it is often necessary to obtain all models oriented the
      same way in three dimensions. The problem is not trivial since there exist no 3D
      counterpart of correlation analysis used for 2D images. It is usually solved by
      time consuming trial and error algorithms. RESULTS: 3D density distributions can
      be brought to a 'canonical' orientation. The tensor of inertia of the
      distribution is determined and its eigenvectors are oriented along the coordinate
      axes. The method is fast and essentially free of reference. It is suitable for
      structures whose inertial axes do not completely degenerate as they do in
      icosahedral viruses or if symmetry is cubic. Applications are presented for
      asymmetric objects and for molecules possessing symmetry axes higher than
      twofold. IMPLEMENTATION: The implementation simply requires the accumulation of
      the inertial tensor and its diagonalisation. Volume data rotation has been
      already illustrated in this journal by the authors.

PMID- 11222263
TI  - What are the baselines for protein fold recognition?
AB  - MOTIVATION: What constitutes a baseline level of success for protein fold
      recognition methods? As fold recognition benchmarks are often presented without
      any thought to the results that might be expected from a purely random set of
      predictions, an analysis of fold recognition baselines is long overdue. Given
      varying amounts of basic information about a protein-ranging from the length of
      the sequence to a knowledge of its secondary structure-to what extent can the
      fold be determined by intelligent guesswork? Can simple methods that make use of
      secondary structure information assign folds more accurately than purely random
      methods and could these methods be used to construct viable hierarchical
      classifications? EXPERIMENTS PERFORMED: A number of rapid automatic methods which
      score similarities between protein domains were devised and tested. These methods
      ranged from those that incorporated no secondary structure information, such as
      measuring absolute differences in sequence lengths, to more complex alignments of
      secondary structure elements. Each method was assessed for accuracy by comparison
      with the Class Architecture Topology Homology (CATH) classification. Methods were
      rated against both a random baseline fold assignment method as a lower control
      and FSSP as an upper control. Similarity trees were constructed in order to
      evaluate the accuracy of optimum methods at producing a classification of
      structure. RESULTS: Using a rigorous comparison of methods with CATH, the random
      fold assignment method set a lower baseline of 11% true positives allowing for 3%
      false positives and FSSP set an upper benchmark of 47% true positives at 3% false
      positives. The optimum secondary structure alignment method used here achieved
      27% true positives at 3% false positives. Using a less rigorous Critical
      Assessment of Structure Prediction (CASP)-like sensitivity measurement the random
      assignment achieved 6%, FSSP-59% and the optimum secondary structure alignment
      method-32%. Similarity trees produced by the optimum method illustrate that these
      methods cannot be used alone to produce a viable protein structural
      classification system. CONCLUSIONS: Simple methods that use perfect secondary
      structure information to assign folds cannot produce an accurate protein
      taxonomy, however they do provide useful baselines for fold recognition. In terms
      of a typical CASP assessment our results suggest that approximately 6% of targets
      with folds in the databases could be assigned correctly by randomly guessing, and
      as many as 32% could be recognised by trivial secondary structure comparison
      methods, given knowledge of their correct secondary structures.

PMID- 11222264
TI  - A Web interface generator for molecular biology programs in Unix.
AB  - MOTIVATION: Almost all users encounter problems using sequence analysis programs.
      Not only are they difficult to learn because of the parameters, syntax and
      semantic, but many are different. That is why we have developed a Web interface
      generator for more than 150 molecular biology command-line driven programs,
      including: phylogeny, gene prediction, alignment, RNA, DNA and protein analysis,
      motif discovery, structure analysis and database searching programs. The
      generator uses XML as a high-level description language of the legacy software
      parameters. Its aim is to provide users with the equivalent of a basic Unix
      environment, with program combination, customization and basic scripting through
      macro registration. RESULTS: The program has been used for three years by about
      15000 users throughout the world; it has recently been installed on other sites
      and evaluated as a standard user interface for EMBOSS programs.

PMID- 11222265
TI  - ISYS: a decentralized, component-based approach to the integration of
      heterogeneous bioinformatics resources.
AB  - MOTIVATION: Heterogeneity of databases and software resources continues to hamper
      the integration of biological information. Top-down solutions are not feasible
      for the full-scale problem of integration across biological species and data
      types. Bottom-up solutions so far have not integrated, in a maximally flexible
      way, dynamic and interactive graphical-user-interface components with data
      repositories and analysis tools. RESULTS: We present a component-based approach
      that relies on a generalized platform for component integration. The platform
      enables independently-developed components to synchronize their behavior and
      exchange services, without direct knowledge of one another. An interface-based
      data model allows the exchange of information with minimal component
      interdependency. From these interactions an integrated system results, which we
      call ISYSf1.gif" BORDER="0">. By allowing services to be discovered dynamically
      based on selected objects, ISYS encourages a kind of exploratory navigation that
      we believe to be well-suited for applications in genomic research.

PMID- 11222266
TI  - Transcription-associated protein families are primarily taxon-specific.
AB  - The mechanisms controlling gene regulation appear to be fundamentally different
      in eukaryotes and prokaryotes (Struhl (1999) CELL, 98, 1-4). To investigate this
      diversity further, we have analysed the distribution of all known transcription
      associated proteins (TAPs), as reflected by sequence database annotations. Our
      results for the primary phylogenetic domains (Archaea, Bacteria and Eukaryota)
      show that TAP families are mostly taxon-specific and very few transcriptional
      regulators are common across these domains.

PMID- 11222267
TI  - PrimeArray: genome-scale primer design for DNA-microarray construction.
AB  - PrimeArray is a Windows program that computes oligonuceotide primer pairs for
      genome-scale gene amplification by the Polymerase Chain Reaction (PCR). The
      program supports the automated extraction of coding sequences (CDS) from various
      input-file formats and allows highly automated primer pair-optimization.

PMID- 11222268
TI  - The PACRAT system: an extensible WWW-based system for correlated sequence
      retrieval, storage and analysis.
AB  - With PACRAT (Patterns, Analyses, Correlations. Remote Archive Testbed) we present
      an online database solution to the problem of accessing high-confidence sequences
      with specific relationships to classes of genes, such as upstream intergenic
      regions attached to tRNA genes. In addition the software contains a data
      warehousing and analysis-facilitating suite to streamline the process of
      analyzing the collected data. An unexpected additional benefit of the system is
      that it also provides easy access to sequences of lower confidence, and may be of
      assistance in such things as resolving ORF-call conflicts in genomic annotation
      projects.

PMID- 11222269
TI  - EASY--an Expert Analysis SYstem for interpreting database search outputs.
AB  - With the ever-increasing need to handle large volumes of sequence data
      efficiently and reliably, we have developed the EASY system for performing
      combined protein sequence and pattern database searches. EASY runs searches
      simultaneously and distils results into a concise 1-line diagnosis. By bringing
      together results of several different analyses, EASY provides a rapid means of
      evaluating biological significance, minimising the risk of inferring false
      relationships, for example from relying exclusively on top BLAST hits. The
      program has been tested using a variety of protein families and was instrumental
      in resolving family assignments in a major update of the PRINTS database.

PMID- 11222271
TI  - Reaction complexity of flowing human blood.

PMID- 11222272
TI  - Photosynthetic electron transfer controlled by protein relaxation: analysis by
      Langevin stochastic approach.
AB  - Relaxation processes in proteins range in time from picoseconds to seconds.
      Correspondingly, biological electron transfer (ET) could be controlled by slow
      protein relaxation. We used the Langevin stochastic approach to describe this
      type of ET dynamics. Two different types of kinetic behavior were revealed,
      namely: oscillating ET (that could occur at picoseconds) and monotonically
      relaxing ET. On a longer time scale, the ET dynamics can include two different
      kinetic components. The faster one reflects the initial, nonadiabatic ET, whereas
      the slower one is governed by the medium relaxation. We derived a simple relation
      between the relative extents of these components, the change in the free energy
      (DeltaG), and the energy of the slow reorganization Lambda. The rate of ET was
      found to be determined by slow relaxation at -DeltaG < or = Lambda. The
      application of the developed approach to experimental data on ET in the bacterial
      photosynthetic reaction centers allowed a quantitative description of the
      oscillating features in the primary charge separation and yielded values of
      Lambda for the slower low-exothermic ET reactions. In all cases but one, the
      obtained estimates of Lambda varied in the range of 70-100 meV. Because the vast
      majority of the biological ET reactions are only slightly exothermic (DeltaG > or
      = -100 meV), the relaxationally controlled ET is likely to prevail in proteins.

PMID- 11222273
TI  - Surface-mediated control of blood coagulation: the role of binding site densities
      and platelet deposition.
AB  - A mathematical model of the extrinsic or tissue factor (TF) pathway of blood
      coagulation is formulated and results from a computational study of its behavior
      are presented. The model takes into account plasma-phase and surface-bound
      enzymes and zymogens, coagulation inhibitors, and activated and unactivated
      platelets. It includes both plasma-phase and membrane-phase reactions, and
      accounts for chemical and cellular transport by flow and diffusion, albeit in a
      simplified manner by assuming the existence of a thin, well-mixed fluid layer,
      near the surface, whose thickness depends on flow. There are three main
      conclusions from these studies. (i) The model system responds in a threshold
      manner to changes in the availability of particular surface binding sites; an
      increase in TF binding sites, as would occur with vascular injury, changes the
      system's production of thrombin dramatically. (ii) The model suggests that
      platelets adhering to and covering the subendothelium, rather than chemical
      inhibitors, may play the dominant role in blocking the activity of the TF:VIIa
      enzyme complex. This, in turn, suggests that a role of the IXa-tenase pathway for
      activating factor X to Xa is to continue factor Xa production after platelets
      have covered the TF:VIIa complexes on the subendothelium. (iii) The model gives a
      kinetic explanation of the reduced thrombin production in hemophilias A and B.

PMID- 11222274
TI  - Statistical thermodynamics of membrane bending-mediated protein-protein
      attractions.
AB  - Highly wedge-shaped integral membrane proteins, or membrane-adsorbed proteins can
      induce long-ranged deformations. The strain in the surrounding bilayer creates
      relatively long-ranged forces that contribute to interactions with nearby
      proteins. In contrast, to direct short-ranged interactions such as van der
      Waal's, hydrophobic, or electrostatic interactions, both local membrane Gaussian
      curvature and protein ellipticity can induce forces acting at distances of up to
      a few times their typical radii. These forces can be attractive or repulsive,
      depending on the proteins' shape, height, contact angle with the bilayer, and a
      pre-existing local membrane curvature. Although interaction energies are not
      pairwise additive, for sufficiently low protein density, thermodynamic properties
      depend only upon pair interactions. Here, we compute pair interaction potentials
      and entropic contributions to the two-dimensional osmotic pressure of a
      collection of noncircular proteins. For flat membranes, bending rigidities of
      approximately 100k(B)T, moderate ellipticities, and large contact angle proteins,
      we find thermally averaged attractive interactions of order k(B)T. These
      interactions may play an important role in the intermediate stages of protein
      aggregation. Numerous biological processes where membrane bending-mediated
      interactions may be relevant are cited, and possible experiments are discussed.

PMID- 11222275
TI  - Bayesian restoration of ion channel records using hidden Markov models.
AB  - Hidden Markov models have been used to restore recorded signals of single ion
      channels buried in background noise. Parameter estimation and signal restoration
      are usually carried out through likelihood maximization by using variants of the
      Baum-Welch forward-backward procedures. This paper presents an alternative
      approach for dealing with this inferential task. The inferences are made by using
      a combination of the framework provided by Bayesian statistics and numerical
      methods based on Markov chain Monte Carlo stochastic simulation. The reliability
      of this approach is tested by using synthetic signals of known characteristics.
      The expectations of the model parameters estimated here are close to those
      calculated using the Baum-Welch algorithm, but the present methods also yield
      estimates of their errors. Comparisons of the results of the Bayesian Markov
      Chain Monte Carlo approach with those obtained by filtering and thresholding
      demonstrate clearly the superiority of the new methods.

PMID- 11222276
TI  - Combined Monte Carlo and molecular dynamics simulation of hydrated lipid
      cholesterol lipid bilayers at low cholesterol concentration.
AB  - We have applied a hybrid equilibration and sampling procedure for the atomic
      level simulation of a hydrated lipid bilayer to systems consisting of dipalmitoyl
      phosphatidylcholine (DPPC) and cholesterol, and palmitoyl-oleyl
      phosphatidylcholine (POPC) at low (approximately 6%) cholesterol concentration.
      The procedure is applied to bilayers of 94 molecules of DPPC, 6 molecules of
      cholesterol, and 3205 water molecules, and to bilayers of 120 molecules of POPC,
      8 molecules of cholesterol, and 4268 water molecules, at a temperature of 325 K.
      After equilibration, three separate 400-ps continuous molecular dynamics runs,
      separated by 10,000 configurational bias Monte Carlo steps, were carried out for
      each system. Properties of the systems were calculated and averaged over the
      three separate runs. Results of the simulations are presented and compared with
      experimental data and with other recent simulations of DPPC and cholesterol, and
      of pure DPPC, and pure POPC. Certain properties of the bilayers are
      indistinguishable from cholesterol-free bilayers, including lateral diffusion and
      electron density. Other properties, most notably the order parameter profile,
      show the effect of cholesterol even at low concentrations.

PMID- 11222277
TI  - Protein flexibility from the dynamical transition: a force constant analysis.
AB  - A standard analysis of the scattered neutron incoherent elastic intensity
      measured with very good energy resolution yields elastic scans, i.e., mean-square
      displacements of atomic motions (in a pico to nanosecond time scale) in a sample
      as a function of temperature. This provides a quick way for characterizing the
      dynamical behavior of biological macromolecules, such behavior being correlated
      with biological function and activity. Elastic scans of proteins exhibit a
      dynamical transition at approximately 200 K, marking a cross-over in molecular
      fluctuations between harmonic and nonharmonic dynamical regimes. This paper
      presents an approach allowing analysis of the elastic scan in terms of force
      constants and related parameters, such as the free energy barrier DeltaG at the
      transition. We find that the increased protein flexibility beyond the dynamical
      transition is associated with DeltaG approximately equals RT and effective force
      constants of the order of 0.1-3 N/m. The analysis provides a set of parameters
      for characterizing molecular resilience and exploring relations among dynamics,
      function, and activity in proteins.

PMID- 11222278
TI  - Dynamic contact forces on leukocyte microvilli and their penetration of the
      endothelial glycocalyx.
AB  - We develop a theoretical model to examine the combined effect of gravity and
      microvillus length heterogeneity on tip contact force (F(m)(z)) during free
      rolling in vitro, including the initiation of L-, P-, and E-selectin tethers and
      the threshold behavior at low shear. F (m)(z) grows nonlinearly with shear. At
      shear stress of 1 dyn/cm(2), F(m)(z) is one to two orders of magnitude greater
      than the 0.1 pN force for gravitational settling without flow. At shear stresses
      > 0.2 dyn/cm(2) only the longest microvilli contact the substrate; hence at the
      shear threshold (0.4 dyn/cm(2) for L-selectin), only 5% of microvilli can
      initiate tethering interaction. The characteristic time for tip contact is
      surprisingly short, typically 0.1-1 ms. This model is then applied in vivo to
      explore the free-rolling interaction of leukocyte microvilli with endothelial
      glycocalyx and the necessary conditions for glycocalyx penetration to initiate
      cell rolling. The model predicts that for arteriolar capillaries even the longest
      microvilli cannot initiate rolling, except in regions of low shear or flow
      reversal. In postcapillary venules, where shear stress is approximately 2
      dyn/cm(2), tethering interactions are highly likely, provided that there are some
      relatively long microvilli. Once tethering is initiated, rolling tends to ensue
      because F(m)(z) and contact duration will both increase substantially to
      facilitate glycocalyx penetration by the shorter microvilli.

PMID- 11222279
TI  - Calculated pH-dependent population and protonation of carbon-monoxy-myoglobin
      conformers.
AB  - X-ray structures of carbonmonoxymyoglobin (MbCO) are available for different pH
      values. We used conventional electrostatic continuum methods to calculate the
      titration behavior of MbCO in the pH range from 3 to 7. For our calculations, we
      considered five different x-ray structures determined at pH values of 4, 5, and
      6. We developed a Monte Carlo method to sample protonation states and
      conformations at the same time so that we could calculate the population of the
      considered MbCO structures at different pH values and the titration behavior of
      MbCO for an ensemble of conformers. To increase the sampling efficiency, we
      introduced parallel tempering in our Monte Carlo method. The calculated
      population probabilities show, as expected, that the x-ray structures determined
      at pH 4 are most populated at low pH, whereas the x-ray structure determined at
      pH 6 is most populated at high pH, and the population of the x-ray structures
      determined at pH 5 possesses a maximum at intermediate pH. The calculated
      titration behavior is in better agreement with experimental results compared to
      calculations using only a single conformation. The most striking feature of pH
      dependent conformational changes in MbCO-the rotation of His-64 out of the CO
      binding pocket-is reproduced by our calculations and is correlated with a
      protonation of His-64, as proposed earlier.

PMID- 11222280
TI  - Molecular dynamics study of the energetic, mechanistic, and structural
      implications of a closed phosphate tube in ncd.
AB  - The switch 1 region of myosin forms a lid over the nucleotide phosphates as part
      of a structure known as the phosphate-tube. The homologous region in kinesin
      family motors is more open, not interacting with the nucleotide. We used
      molecular dynamics (MD) simulations to examine a possible displacement of switch
      1 of the microtubule motor, ncd, from the open conformation to the closed
      conformation seen in myosin. MD simulations were done of both the open and the
      closed conformations, with either MgADP or MgATP at the active site. All MD
      structures were stable at 300 K for 500 ps, implying that the open and closed
      conformers all represented local minima on a global free energy surface. Free
      energy calculations indicated that the open structure was energetically favored
      with MgADP at the active site, suggesting why only the open structure has been
      captured in crystallographic work. With MgATP, the closed and open structures had
      roughly equal energies. Simulated annealing MD showed the transformation from the
      closed phosphate-tube ncd structure to an open configuration. The MD simulations
      also showed that the coordination of switch 1 to the nucleotide dramatically
      affected the position of both the bound nucleotide and switch 2 and that a closed
      phosphate-tube may be necessary for catalysis.

PMID- 11222282
TI  - Irreversibility in unbranched pathways: preferred positions based on regulatory
      considerations.
AB  - It has been observed experimentally that most unbranched biosynthetic pathways
      have irreversible reactions near their beginning, many times at the first step.
      If there were no functional reasons for this fact, then one would expect
      irreversible reactions to be equally distributed among all positions in such
      pathways. Since this is not the case, we have attempted to identify functional
      consequences of having an irreversible reaction early in the pathway. We
      systematically varied the position of the irreversible reaction in model pathways
      and compared the resulting systemic behavior according to several criteria for
      functional effectiveness, using the method of mathematically controlled
      comparisons. This technique minimizes extraneous differences in systemic behavior
      and identifies those that are fundamental. Our results show that a pathway with
      an irreversible reaction located at the first step, and with all other reactions
      reversible, is on average better than an otherwise equivalent pathway with all
      reactions reversible, which in turn is on average better than an otherwise
      equivalent pathway with an irreversible reaction located at any step other than
      the first. Pathways with an irreversible first reaction and low concentrations of
      intermediates (one of the primary criteria for functional effectiveness) exhibit
      the following profile when compared to fully reversible pathways: changes in the
      concentration of intermediates in response to changes in the level of initial
      substrate are equally low, the robustness of the intermediate concentrations and
      of the flux is similar, the margins of stability are similar, flux is more
      responsive to changes in demand for end product, intermediate concentrations are
      less responsive to changes in demand for end product, and transient times are
      shorter. These results provide a functional rationale for the positioning of
      irreversible reactions at the beginning of unbranched biosynthetic pathways.

PMID- 11222281
TI  - Modeling Pseudomonas syringae ice-nucleation protein as a beta-helical protein.
AB  - Antifreeze proteins (AFPs) inhibit the growth of ice, whereas ice-nucleation
      proteins (INPs) promote its formation. Although the structures of several AFPs
      are known, the structure of INP has been modeled thus far because of the
      difficulty in determining membrane protein structures. Here, we present a novel
      model of an INP structure from Pseudomonas syringae based on comparison with two
      newly determined insect AFP structures. The results suggest that both this class
      of AFPs and INPs may have a similar beta-helical fold and that they could
      interact with water through the repetitive TXT motif. By theoretical arguments,
      we show that the distinguishing feature between an ice inhibitor and an ice
      nucleator lies in the size of the ice-interacting surface. For INPs, the larger
      surface area acts as a template that is larger than the critical ice embryo
      surface area required for growth. In contrast, AFPs are small enough so that they
      bind to ice and inhibit further growth without acting as a nucleator.

PMID- 11222283
TI  - Flexible polymer-induced condensation and bundle formation of DNA and F-actin
      filaments.
AB  - A simple semi-empirical theory is developed for the ionic strength dependence of
      the flexible polymer-induced condensation of semiflexible polyelectrolytes such
      as DNA and F-actin filaments. Critical concentrations of flexible polymer needed
      for condensation are calculated by comparing the free energies of inserting the
      semiflexible polyelectrolytes in a solution of flexible polymers, respectively,
      in their free state, and in their condensed state. Predictions of the theory are
      compared to experimental data on the condensation of DNA and F-actin filaments
      induced by the flexible polymer poly(ethylene oxide). The theory also predicts
      that reentrant decollapse is possible at low ionic strength and high
      concentrations of flexible polymer, as observed for DNA.

PMID- 11222284
TI  - Excitation wave propagation as a possible mechanism for signal transmission in
      pancreatic islets of Langerhans.
AB  - In response to glucose application, beta-cells forming pancreatic islets of
      Langerhans start bursting oscillations of the membrane potential and
      intracellular calcium concentration, inducing insulin secretion by the cells.
      Until recently, it has been assumed that the bursting activity of beta-cells in a
      single islet of Langerhans is synchronized across the whole islet due to coupling
      between the cells. However, time delays of several seconds in the activity of
      distant cells are usually observed in the islets of Langerhans, indicating that
      electrical/calcium wave propagation through the islets can occur. This work
      presents both experimental and theoretical evidence for wave propagation in the
      islets of Langerhans. Experiments with Fura-2 fluorescence monitoring of
      spatiotemporal calcium dynamics in the islets have clearly shown such wave
      propagation. Furthermore, numerical simulations of the model describing a cluster
      of electrically coupled beta-cells have supported our view that the
      experimentally observed calcium waves are due to electric pulses propagating
      through the cluster. This point of view is also supported by independent
      experimental results. Based on the model equations, an approximate analytical
      expression for the wave velocity is introduced, indicating which parameters can
      alter the velocity. We point to the possible role of the observed waves as
      signals controlling the insulin secretion inside the islets of Langerhans, in
      particular, in the regions that cannot be reached by any external stimuli such as
      high glucose concentration outside the islets.

PMID- 11222285
TI  - Side-chain ionization states in a potassium channel.
AB  - KcsA is a bacterial K+ channel that is gated by pH. Continuum dielectric
      calculations on the crystal structure of the channel protein embedded in a low
      dielectric slab suggest that side chains E71 and D80 of each subunit, which lie
      adjacent to the selectivity filter region of the channel, form a proton-sharing
      pair in which E71 is neutral (protonated) and D80 is negatively charged at pH 7.
      When K+ ions are introduced into the system at their crystallographic positions
      the pattern of proton sharing is altered. The largest perturbation is for a K+
      ion at site S3, i.e., interacting with the carbonyls of T75 and V76. The presence
      of multiple K+ ions in the filter increases the probability of E71 being ionized
      and of D80 remaining neutral (i.e., protonated). The ionization states of the
      protein side chains influence the potential energy profile experienced by a K+
      ion as it is translated along the pore axis. In particular, the ionization state
      of the E71-D80 proton-sharing pair modulates the shape of the potential profile
      in the vicinity of the selectivity filter. Such reciprocal effects of ion
      occupancy on side-chain ionization states, and of side-chain ionization states on
      ion potential energy profiles will complicate molecular dynamics simulations and
      related studies designed to calculate ion permeation energetics.

PMID- 11222286
TI  - Voltage-dependent membrane capacitance in rat pituitary nerve terminals due to
      gating currents.
AB  - We investigated the voltage dependence of membrane capacitance of pituitary nerve
      terminals in the whole-terminal patch-clamp configuration using a lock-in
      amplifier. Under conditions where secretion was abolished and voltage-gated
      channels were blocked or completely inactivated, changes in membrane potential
      still produced capacitance changes. In terminals with significant sodium
      currents, the membrane capacitance showed a bell-shaped dependence on membrane
      potential with a peak at approximately -40 mV as expected for sodium channel
      gating currents. The voltage-dependent part of the capacitance showed a strong
      correlation with the amplitude of voltage-gated Na+ currents and was markedly
      reduced by dibucaine, which blocks sodium channel current and gating charge
      movement. The frequency dependence of the voltage-dependent capacitance was
      consistent with sodium channel kinetics. This is the first demonstration of
      sodium channel gating currents in single pituitary nerve terminals. The gating
      currents lead to a voltage- and frequency-dependent capacitance, which can be
      well resolved by measurements with a lock-in amplifier. The properties of the
      gating currents are in excellent agreement with the properties of ionic Na+
      currents of pituitary nerve terminals.

PMID- 11222287
TI  - The sodium pump modulates the influence of I(Na) on [Ca2+]i transients in mouse
      ventricular myocytes.
AB  - To investigate whether activity of the sarcolemmal Na pump modulates the
      influence of sodium current on excitation-contraction (E-C) coupling, we measured
      [Ca(2+)](i) transients (fluo-3) in single voltage-clamped mouse ventricular
      myocytes ([Na+](pip) = 15 or 0 mM) when the Na pump was activated (4.4 mM
      K(+)(o)) and during abrupt inhibition of the pump by exposure to 0 K with a rapid
      solution-switcher device. After induction of steady state [Ca2+](i) transients by
      conditioning voltage pulses (0.25 Hz), inhibition of the Na pump for 1.5 s
      immediately before and continuing during a voltage pulse (200 ms, -80 to 0 mV)
      caused a significant increase (15 +/- 2%; n = 16; p < 0.01) in peak systolic
      [Ca2+](i) when [Na+](pip) was 15 mM. In the absence of sodium current (I(Na),
      which was blocked by 60 microM tetrodotoxin (TTX)), inhibition of the Na pump
      immediately before and during a voltage pulse did not result in an increase in
      peak systolic [Ca2+](i). Abrupt blockade of I(Na) during a single test pulse with
      TTX caused a slight decrease in peak [Ca2+](i), whether the pump was active (9%)
      or inhibited (10%). With the reverse-mode Na/Ca exchange inhibited by KB-R 7943,
      inhibition of the Na pump failed to increase the magnitude of the peak systolic
      [Ca2+](i) (4 +/- 1%; p = NS) when [Na+](pip) was 15 mM. When [Na+](pip) was 0 mM,
      the amplitude of the peak systolic [Ca2+](i) was not altered by abrupt inhibition
      of the Na pump immediately before and during a voltage pulse. These findings in
      adult mouse ventricular myocytes indicate the Na pump can modulate the influence
      of I(Na) on E-C coupling in a single beat and provide additional evidence for the
      existence of Na fuzzy space, where [Na+] can significantly modulate Ca2+ influx
      via reverse Na/Ca exchange.

PMID- 11222288
TI  - Alternatively spliced alpha(1G) (Ca(V)3.1) intracellular loops promote specific T
      type Ca(2+) channel gating properties.
AB  - At least three genes encode T-type calcium channel alpha(1) subunits, and
      identification of cDNA transcripts provided evidence that molecular diversity of
      these channels can be further enhanced by alternative splicing mechanisms,
      especially for the alpha(1G) subunit (Ca(V)3.1). Using whole-cell patch-clamp
      procedures, we have investigated the electrophysiological properties of five
      isoforms of the human alpha(1G) subunit that display a distinct III-IV linker,
      namely, alpha(1G-a), alpha(1G-b), and alpha(1G-bc), as well as a distinct II-III
      linker, namely, alpha(1G-ae), alpha(1G-be), as expressed in HEK-293 cells. We
      report that insertion e within the II-III linker specifically modulates
      inactivation, steady-state kinetics, and modestly recovery from inactivation,
      whereas alternative splicing within the III-IV linker affects preferentially
      kinetics and voltage dependence of activation, as well as deactivation and
      inactivation. By using voltage-clamp protocols mimicking neuronal activities,
      such as cerebellar train of action potentials and thalamic low-threshold spike,
      we describe that inactivation properties of alpha(1G-a) and alpha(1G-ae) isoforms
      can support channel behaviors reminiscent to those described in native neurons.
      Altogether, these data demonstrate that expression of distinct variants for the T
      type alpha(1G) subunit can account for specific low-voltage-activated currents
      observed in neuronal tissues.

PMID- 11222289
TI  - Synapse-specific contribution of the variation of transmitter concentration to
      the decay of inhibitory postsynaptic currents.
AB  - Synaptic transmission is characterized by a remarkable trial-to-trial variability
      in the postsynaptic response, influencing the way in which information is
      processed in neuronal networks. This variability may originate from the
      probabilistic nature of quantal transmitter release, from the stochastic behavior
      of the receptors, or from the fluctuation of the transmitter concentration in the
      cleft. We combined nonstationary noise analysis and modeling techniques to
      estimate the contribution of transmitter fluctuation to miniature inhibitory
      postsynaptic current (mIPSC) variability. A substantial variability
      (approximately 30%) in mIPSC decay was found in all cell types studied
      (neocortical layer2/3 pyramidal cells, granule cells of the olfactory bulb, and
      interneurons of the cerebellar molecular layer). This large variability was not
      solely the consequence of the expression of multiple types of GABA(A) receptors,
      as a similar mIPSC decay variability was observed in cerebellar interneurons that
      express only a single type (alpha(1)beta(2)gamma(2)) of GABA(A) receptor. At
      large synapses on these cells, all variance in mIPSC decay could be accounted for
      by the stochastic behavior of approximately 36 pS channels, consistent with the
      conductance of alpha(1)beta(2)gamma(2) GABA(A) receptors at physiological
      temperatures. In contrast, at small synapses, a significant amount of variability
      in the synaptic cleft GABA transient had to be present to account for the
      additional variance in IPSC decay over that produced by stochastic channel
      openings. Thus, our results suggest a synapse-specific contribution of the
      variation of the spatiotemporal profile of GABA to the decay of IPSCs.

PMID- 11222291
TI  - Multiple binding sites for melatonin on Kv1.3.
AB  - Melatonin is a small amino acid derivative hormone of the pineal gland. Melatonin
      quickly and reversibly blocked Kv1.3 channels, the predominant voltage-gated
      potassium channel in human T-lymphocytes, acting from the extracellular side. The
      block did not show state or voltage dependence and was associated with an
      increased inactivation rate of the current. A half-blocking concentration of 1.5
      mM was obtained from the reduction of the peak current. We explored several
      models to describe the stoichiometry of melatonin-Kv1.3 interaction considering
      one or four independent binding sites per channel. The model in which the
      occupancy of one of four binding sites by melatonin is sufficient to block the
      channels gives the best fit to the dose-response relationship, although all four
      binding sites can be occupied by the drug. The dissociation constant for the
      individual binding sites is 8.11 mM. Parallel application of charybdotoxin and
      melatonin showed that both compounds can simultaneously bind to the channels,
      thereby localizing the melatonin binding site out of the pore region. However,
      binding of tetraethylammonium to its receptor decreases the melatonin affinity,
      and vice versa. Thus, the occupancy of the two separate receptor sites
      allosterically modulates each other.

PMID- 11222290
TI  - Cytoplasmic polyamines as permeant blockers and modulators of the voltage-gated
      sodium channel.
AB  - We report that voltage-gated Na+ channels (Na(V)) from rat muscle (mu1) expressed
      in HEK293 cells exhibit anomalous rectification of whole-cell outward current
      under conditions of symmetrical Na+. This behavior gradually fades with time
      after membrane break-in, as if a diffusible blocking substance in the cytoplasm
      is slowly diluted by the pipette solution. The degree of such block and
      rectification is markedly altered by various mutations of the conserved Lys(III)
      residue in Domain III of the Na(V) channel selectivity filter (DEKA locus), a
      principal determinant of inorganic ion selectivity and organic cation permeation.
      Using whole-cell and macropatch recording techniques, we show that two ubiquitous
      polyamines, spermine and spermidine, are potent voltage-dependent cytoplasmic
      blockers of mu1 Na(V) current that exhibit relief of block at high positive
      voltage, a phenomenon that is also enhanced by certain mutations of the Lys(III)
      residue. In addition, we find that polyamines alter the apparent rate of
      macroscopic inactivation and exhibit a use-dependent blocking phenomenon
      reminiscent of the action of local anesthetics. In the presence of a
      physiological Na+/K+ gradient, spermine also inhibits inward Na(V) current and
      shifts the voltage dependence of activation and inactivation. Similarities
      between the endogenous blocking phenomenon observed in whole cells and polyamine
      block characterized in excised patches suggest that polyamines or related
      metabolites may function as endogenous modulators of Na(V) channel activity.

PMID- 11222292
TI  - Apparent intracellular Mg2+ buffering in neurons of the leech Hirudo medicinalis.
AB  - The apparent intracellular Mg2+ buffering, or muffling (sum of processes that
      damp changes in the free intracellular Mg2+ concentration, [Mg2+](i), e.g.,
      buffering, extrusion, and sequestration), was investigated in Retzius neurons of
      the leech Hirudo medicinalis by iontophoretic injection of H+, OH-, or Mg2+.
      Simultaneously, changes in intracellular pH and the intracellular Mg2+, Na+, or
      K+ concentration were recorded with triple-barreled ion-selective
      microelectrodes. Cell volume changes were monitored measuring the
      tetramethylammonium (TMA) concentration in TMA-loaded neurons. Control
      measurements were carried out in electrolyte droplets (diameter 100-200 microm)
      placed on a silver wire under paraffin oil. Droplets with or without ATP, the
      presumed major intracellular Mg2+ buffer, were used to quantify the pH dependence
      of Mg2+ buffering and to determine the transport index of Mg2+ during
      iontophoretic injection. The observed pH dependence of [Mg2+](i) corresponded to
      what would be expected from Mg2+ buffering through ATP. The quantity of Mg2+
      muffling, however, was considerably larger than what would be expected if ATP
      were the sole Mg2+ buffer. From the decrease in Mg2+ muffling in the nominal
      absence of extracellular Na+ it was estimated that almost 50% of the ATP
      independent muffling is due to the action of Na+/Mg2+ antiport.

PMID- 11222293
TI  - Quantal and non-quantal current and potential fields around individual
      sympathetic varicosities on release of ATP.
AB  - The electrical phenomena that occur at sympathetic varicosities due to the
      release of ATP include spontaneous and evoked excitatory junction potentials
      (SEJPs and EJPs; recorded with an intracellular electrode) as well as fast and
      slow excitatory junctional currents (EJCs; recorded with a loose-patch electrode
      placed over varicosities). The electrical analysis of these transients is
      hampered by lack of a detailed theory describing how current and potential fields
      are generated upon the release of a quantum of ATP. Here, we supply such a theory
      and develop a computational model for the electrical properties of a smooth
      muscle syncytium placed within a volume conductor, using a distributed
      representation for the individual muscle cells. The amplitudes and temporal
      characteristics of both SEJPs and fast EJCs are predicted by the theory, but
      those of the slow EJCs are not. It is shown that these slow components cannot
      arise as a consequence of propagation of fast quantal components from their site
      of origin in the muscle syncytium to the point of recording. The possibility that
      slow components arise by a mechanism of transmitter secretion that is different
      from quantal release is examined. Experiments that involve inserting peptide
      fragments of soluble N-ethylmaleimide-sensitive fusion attachment protein (alpha
      SNAP) into varicosities, a procedure that is known to block quantal release, left
      the slow component of release unaffected. This work provides an internally
      consistent description of quantal potential and current fields about the
      varicosities of sympathetic nerve terminals and provides evidence for a non
      quantal form of transmitter release.

PMID- 11222294
TI  - Studies of the structure and organization of cationic lipid bilayer membranes:
      calorimetric, spectroscopic, and x-ray diffraction studies of linear saturated P
      O-ethyl phosphatidylcholines.
AB  - Differential scanning calorimetry, x-ray diffraction, and infrared and (31)P
      nuclear magnetic resonance ((31)P-NMR) spectroscopy were used to examine the
      thermotropic phase behavior and organization of cationic model membranes composed
      of the P-O-ethyl esters of a homologous series of n-saturated 1,2-diacyl
      phosphatidylcholines (Et-PCs). Differential scanning calorimetry studies indicate
      that on heating, these lipids exhibit single highly energetic and cooperative
      endothermic transitions whose temperatures and enthalpies are higher than those
      of the corresponding phosphatidylcholines (PCs). Upon cooling, these Et-PCs
      exhibit two exothermic transitions at temperatures slightly below the single
      endotherm observed upon heating. These cooling exotherms have both been assigned
      to transitions between the liquid-crystalline and gel phases of these lipids by x
      ray diffraction. The x-ray diffraction data also show that unlike the parent PCs,
      the chain-melting phase transition of these Et-PCs involves a direct
      transformation of a chain-interdigitated gel phase to the lamellar liquid
      crystalline phase for the homologous series of n > or = 14. Our (31)P-NMR
      spectroscopic studies indicate that the rates of phosphate headgroup
      reorientation in both gel and liquid-crystalline phases of these lipids are
      comparable to those of the corresponding PC bilayers. However, the shape of the
      (31)P-NMR spectra observed in the interdigitated gel phase indicates that
      phosphate headgroup reorientation is subject to constraints that are not
      encountered in the non-interdigitated gel phases of parent PCs. The infrared
      spectroscopic data indicate that the Et-PCs adopt a very compact form of
      hydrocarbon chain packing in the interdigitated gel phase and that the
      polar/apolar interfacial regions of these bilayers are less hydrated than those
      of corresponding PC bilayers in both the gel and liquid-crystalline phases. Our
      results indicate that esterification of PC phosphate headgroups results in many
      alterations of bilayer physical properties aside from the endowment of a
      positively charged surface. This fact should be considered in assessing the
      interactions of these compounds with naturally occurring lipids and with other
      biological materials.

PMID- 11222295
TI  - Differential interaction of equinatoxin II with model membranes in response to
      lipid composition.
AB  - Equinatoxin II is a 179-amino-acid pore-forming protein isolated from the venom
      of the sea anemone Actinia equina. Large unilamellar vesicles and lipid
      monolayers of different lipid compositions have been used to study its
      interaction with membranes. The critical pressure for insertion is the same in
      monolayers made of phosphatidylcholine or sphingomyelin (approximately 26 mN m(
      1)) and explains why the permeabilization of large unilamellar vesicles by
      equinatoxin II with these lipid compositions is null or moderate. In
      phosphatidylcholine-sphingomyelin (1:1) monolayers, the critical pressure is
      higher (approximately 33 mN m(-1)), thus permitting the insertion of equinatoxin
      II in large unilamellar vesicles, a process that is accompanied by major
      conformational changes. In the presence of vesicles made of phosphatidylcholine,
      a fraction of the protein molecules remains associated with the membranes. This
      interaction is fully reversible, does not involve major conformational changes,
      and is governed by the high affinity for membrane interfaces of the protein
      region comprising amino acids 101-120. We conclude that although the presence of
      sphingomyelin within the membrane creates conditions for irreversible insertion
      and pore formation, this lipid is not essential for the initial partitioning
      event, and its role as a specific receptor for the toxin is not so clear-cut.

PMID- 11222296
TI  - Ultraweak sugar-sugar interactions for transient cell adhesion.
AB  - Carbohydrate-carbohydrate interactions are rarely considered in biologically
      relevant situations such as cell recognition and adhesion. One Ca(2+)-mediated
      homotypic interaction between two Lewis(x) determinants (Le(x)) has been proposed
      to drive cell adhesion in murine embryogenesis. Here, we confirm the existence of
      this specific interaction by reporting the first direct quantitative measurements
      in an environment akin to that provided by membranes. The adhesion between giant
      vesicles functionalized with Le(x) was obtained by micropipette aspiration and
      contact angle measurements. This interaction is below the thermal energy, and
      cell-cell adhesion will require a large number of molecules, as illustrated by
      the Le(x) concentration peak observed at the cell membranes during the morula
      stage of the embryo. This adhesion is ultralow and therefore difficult to
      measure. Such small interactions explain why the concept of specific interactions
      between carbohydrates is often neglected.

PMID- 11222297
TI  - Amyloid-beta peptide assembly: a critical step in fibrillogenesis and membrane
      disruption.
AB  - Identifying the mechanisms responsible for the assembly of proteins into higher
      order structures is fundamental to structural biology and understanding specific
      disease pathways. The amyloid-beta (Abeta) peptide is illustrative in this regard
      as fibrillar deposits of Abeta are characteristic of Alzheimer's disease. Because
      Abeta includes portions of the extracellular and transmembrane domains of the
      amyloid precursor protein, it is crucial to understand how this peptide interacts
      with cell membranes and specifically the role of membrane structure and
      composition on Abeta assembly and cytotoxicity. We describe the results of a
      combined circular dichroism spectroscopy, electron microscopy, and in situ
      tapping mode atomic force microscopy (TMAFM) study of the interaction of soluble
      monomeric Abeta with planar bilayers of total brain lipid extract. In situ
      extended-duration TMAFM provided evidence of membrane disruption via fibril
      growth of initially monomeric Abeta1-40 peptide within the total brain lipid
      bilayers. In contrast, the truncated Abeta1-28 peptide, which lacks the anchoring
      transmembrane domain found in Abeta1-40, self-associates within the lipid
      headgroups but does not undergo fibrillogenesis. These observations suggest that
      the fibrillogenic properties of Abeta peptide are in part a consequence of
      membrane composition, peptide sequence, and mode of assembly within the membrane.

PMID- 11222299
TI  - Association of a fluorescent amphiphile with lipid bilayer vesicles in regions of
      solid-liquid-disordered phase coexistence.
AB  - The effects of solid-fluid phase separations on the kinetics of association of a
      single-chain fluorescent amphiphile were investigated in two different systems:
      pure DMPC (dimyristoylphosphatidylcholine) and a 1:1 mixture of DMPC and DSPC
      (distearoylphosphatidylcholine). In pure DMPC vesicles, solid (s) and fluid
      (l(d)) phases coexist at the phase transition temperature, T(m), whereas a 1:1
      mixture of DMPC and DSPC shows a stable s-l(d) phase separation over a large
      temperature interval. We found that in single-component bilayers, within the main
      phase transition, the experimental kinetics of association are clearly not single
      exponential, the deviation from that function becoming maximal at the T(m). This
      observation can be accounted for by a rate of desorption that is slower than
      desorption from either fluid or solid phases, leaving the rates of insertion
      unchanged, but a treatment in terms of stable fluid and solid domains may not be
      adequate for the analysis of the association of an amphiphile with pure DMPC
      vesicles at the T(m). In DMPC/DSPC mixtures with solid-fluid phase coexistence,
      association occurs overall faster than expected based on phase composition. The
      observed kinetics can be described by an increase in the rate of insertion,
      leaving the desorption rates unchanged. The fast kinetics of insertion of the
      amphiphile into two-phase bilayers in two-component vesicles is attributed to a
      more rapid insertion into defect-rich regions, which are most likely phase
      boundaries between solid and fluid domains. A two-component mixture of lipids
      that shows a stable phase separation between l(d)-s phases over a large
      temperature interval thus behaves very differently from a single-component
      bilayer at the T(m), with respect to insertion of amphiphiles.

PMID- 11222298
TI  - Lipid membrane expansion and micelle formation by polymer-grafted lipids: scaling
      with polymer length studied by spin-label electron spin resonance.
AB  - Spin-label electron spin resonance (ESR) spectroscopy and auxiliary optical
      density measurements are used to study lipid dispersions of N-poly(ethylene
      glycol)-dipalmitoyl phosphatidylethanolamine (PEG:5000-DPPE) mixed with
      dipalmitoyl phosphatidylcholine (DPPC). PEG:5000-DPPE bears a large hydrophilic
      polymer headgroup (with approximately 114 oxyethylene monomers) and is commonly
      used for steric stabilization of liposomes used in drug delivery. Comparison is
      made with results from mixtures of DPPC with polymer lipids bearing shorter
      headgroups (approximately 45 and 8 oxyethylene monomers). ESR spectra of
      phosphatidylcholine spin-labeled on the 5-C atom position of the sn-2 chain are
      shown to reflect the area expansion of the lipid membranes by the lateral
      pressure exerted in the polymer brush, in a way that is consistent with theory.
      The lipid chain packing density at the onset of micelle formation is the same for
      all three PEG-lipids, although the mole fraction at which this occurs differs
      greatly. The mole fraction at onset scales inversely with the size of the polymer
      headgroup, where the experimental exponent of 0.7 is close to theoretical
      predictions (viz. 0.55-0.6). The mole fraction of PEG-lipid at completion of
      micelle formation is more weakly dependent on polymer size, which conforms with
      theoretical predictions. At high mole fractions of PEG:5000-DPPE the dependence
      of lipid packing density on mole fraction is multiphasic, which differs
      qualitatively from the monotonic decrease in packing density found with the
      shorter polymer lipids. Lipid spin-label ESR is an experimental tool that
      complements theoretical analysis using polymer models combined with the lipid
      equation of state.

PMID- 11222300
TI  - Is there a conserved interaction between cardiolipin and the type II bacterial
      reaction center?
AB  - In a recent publication, the structural details of an interaction between the
      Rhodobacter sphaeroides reaction center and the anionic phospholipid
      diphosphatidyl glycerol (cardiolipin) were described (K. E. McAuley, P. K. Fyfe,
      J. P. Ridge, N. W. Isaacs, R. J. Cogdell, and M. R. Jones, 1999, Proc. Natl.
      Acad. Sci. U.S.A. 96:14706-14711). This was the first crystallographic
      description of an interaction between this biologically important lipid and an
      integral membrane protein and was also the first piece of evidence that the
      reaction center has a specific interaction with cardiolipin. We have examined the
      extent to which the residues that interact with the cardiolipin are conserved in
      other species of photosynthetic bacteria with this type of reaction center and
      discuss the possibility that this cardiolipin binding site is a conserved feature
      of these reaction centers. We look at how sequence variations that would affect
      the shape of the cardiolipin binding site might affect the protein-cardiolipin
      interaction, by modeling the binding of cardiolipin to the reaction center from
      Rhodopseudomonas viridis.

PMID- 11222301
TI  - Determination of membrane immersion depth with O(2): a high-pressure (19)F NMR
      study.
AB  - Oxygen is known to partition with an increasing concentration gradient toward the
      hydrophobic membrane interior. At partial pressures (P(O2)) of 100 Atm or more,
      this concentration gradient is sufficient to induce paramagnetic effects that
      depend sensitively on membrane immersion depth. This effect is demonstrated for
      the fluorine nucleus by depth-dependent paramagnetic shifts and spin-lattice
      relaxation rates, using a fluorinated detergent, CF3(CF(2))(5)C(2)H(4)-O-maltose
      (TFOM), reconstituted into a lipid bilayer model membrane system. To interpret
      the spin-lattice relaxation rates (R) in terms of a precise immersion depth, two
      specifically fluorinated cholesterol species (6-fluorocholesterol and 25
      fluorocholesterol), whose membrane immersion depths were independently estimated,
      were studied by (19)F NMR. The paramagnetic relaxation rates, R, of the
      cholesterol species were then used to parameterize a Gaussian profile that
      directly relates R to immersion depth z. This same Gaussian curve could then be
      used to determine the membrane immersion depth of all six fluorinated chain
      positions of TFOM and of two adjacent residues of specifically fluorinated
      analogs of the antibacterial peptide indolicidin. The potential of this method
      for determination of immersion depth and topology of membrane proteins is
      discussed.

PMID- 11222302
TI  - Lipid rafts reconstituted in model membranes.
AB  - One key tenet of the raft hypothesis is that the formation of glycosphingolipid-
      and cholesterol-rich lipid domains can be driven solely by characteristic lipid
      lipid interactions, suggesting that rafts ought to form in model membranes
      composed of appropriate lipids. In fact, domains with raft-like properties were
      found to coexist with fluid lipid regions in both planar supported lipid layers
      and in giant unilamellar vesicles (GUVs) formed from 1) equimolar mixtures of
      phospholipid-cholesterol-sphingomyelin or 2) natural lipids extracted from brush
      border membranes that are rich in sphingomyelin and cholesterol. Employing
      headgroup-labeled fluorescent phospholipid analogs in planar supported lipid
      layers, domains typically several microns in diameter were observed by
      fluorescence microscopy at room temperature (24 degrees C) whereas non-raft
      mixtures (PC-cholesterol) appeared homogeneous. Both raft and non-raft domains
      were fluid-like, although diffusion was slower in raft domains, and the probe
      could exchange between the two phases. Consistent with the raft hypothesis, GM1,
      a glycosphingolipid (GSL), was highly enriched in the more ordered domains and
      resistant to detergent extraction, which disrupted the GSL-depleted phase. To
      exclude the possibility that the domain structure was an artifact caused by the
      lipid layer support, GUVs were formed from the synthetic and natural lipid
      mixtures, in which the probe, LAURDAN, was incorporated. The emission spectrum of
      LAURDAN was examined by two-photon fluorescence microscopy, which allowed
      identification of regions with high or low order of lipid acyl chain alignment.
      In GUVs formed from the raft lipid mixture or from brush border membrane lipids
      an array of more ordered and less ordered domains that were in register in both
      monolayers could reversibly be formed and disrupted upon cooling and heating.
      Overall, the notion that in biomembranes selected lipids could laterally
      aggregate to form more ordered, detergent-resistant lipid rafts into which
      glycosphingolipids partition is strongly supported by this study.

PMID- 11222303
TI  - Axial disposition of myosin heads in isometrically contracting muscles.
AB  - Meridional x-ray diffraction diagrams, recorded with high angular resolution,
      from muscles contracting at the plateau of isometric tension show that the myosin
      diffraction orders are clusters of peaks. These clusters are due to pronounced
      interference effects between the myosin diffracting units on either side of the M
      line. A theoretical analysis based on the polarity of the myosin (and actin)
      filaments shows that it is possible to extract phase information from which the
      axial disposition of the myosin heads can be determined. The results show that
      each head in a crown pair has a distinct structural disposition. It appears that
      only one of the heads in the pair stereospecifically interacts with the thin
      filament at any one time.

PMID- 11222305
TI  - Halide dependence of the halorhodopsin photocycle as measured by time-resolved
      infrared spectra.
AB  - Time-resolved Fourier transform infrared (FTIR) difference spectra of the
      halorhodopsin (hR) photocycle have been collected from 3 micros to 100 ms in
      saturating concentrations of KCl or KBr. Kinetic analysis of these data revealed
      two decay processes, with time constants of tau(1) approximately 150 micros and
      tau(2) approximately 16 ms in the presence of either halide, with tau(2)
      describing the return to the starting (hR) state. Comparison to previous low
      temperature FTIR spectra of hR intermediates confirms that characteristic hK and
      hL spectral features are both present before the tau(1) decay, in a state
      previously defined as hK(L) (Dioumaev, A., and M. Braiman. 1997. Photochem.
      Photobiol. 66:755-763). However, the relative sizes of these features depend on
      which halide is present. In Br-, the hL features are clearly more dominant than
      in Cl-. Therefore, the state present before tau(1) is probably best described as
      an hK(L)/hL(1) equilibrium, instead of a single hK(L) state. Different halides
      affect the relative amounts of hK(L) and hL(1) present, i.e., Cl- produces a much
      more significant back-reaction from hL(1) to hK(L) than does Br-. The halide
      dependence of this back-reaction could therefore explain the halide selectivity
      of the halorhodopsin anion pump.

PMID- 11222304
TI  - Unfolding of titin domains explains the viscoelastic behavior of skeletal
      myofibrils.
AB  - The elastic section of the giant muscle protein titin contains many
      immunoglobulin-like domains, which have been shown by single-molecule mechanical
      studies to unfold and refold upon stretch-release. Here we asked whether the
      mechanical properties of Ig domains and/or other titin regions could be
      responsible for the viscoelasticity of nonactivated skeletal-muscle sarcomeres,
      particularly for stress relaxation and force hysteresis. We show that isolated
      psoas myofibrils respond to a stretch-hold protocol with a characteristic force
      decay that becomes more pronounced following stretch to above 2.6-microm
      sarcomere length. The force decay was readily reproducible by a Monte Carlo
      simulation taking into account both the kinetics of Ig-domain unfolding and the
      worm-like-chain model of entropic elasticity used to describe titin's elastic
      behavior. The modeling indicated that the force decay is explainable by the
      unfolding of only a very small number of Ig domains per titin molecule. The
      simulation also predicted that a unique sequence in titin, the PEVK domain, may
      undergo minor structural changes during sarcomere extension. Myofibrils subjected
      to 1-Hz cycles of stretch-release exhibited distinct hysteresis that persisted
      during repetitive measurements. Quick stretch-release protocols, in which
      variable pauses were introduced after the release, revealed a two-exponential
      time course of hysteresis recovery. The rate constants of recovery compared well
      with the refolding rates of Ig-like or fibronectin-like domains measured by
      single-protein mechanical analysis. These findings suggest that in the sarcomere,
      titin's Ig-domain regions may act as entropic springs capable of adjusting their
      contour length in response to a stretch.

PMID- 11222306
TI  - Conformational disorder of proteins assessed by real-space molecular dynamics
      refinement.
AB  - Motion is critical to the function of many proteins, but much more difficult to
      study than structure. Due to lack of easy alternatives, although there are
      inherent limitations, there have been several prior attempts to extract some
      information from the Bragg scattering in conventional diffraction patterns. Bragg
      diffraction reflects only a small proportion of a protein's motion and disorder,
      so fitted values likely underestimate reality. However, this work shows that the
      fitted estimates should be even smaller, because current methods of refinement
      over-fit the Bragg diffraction, leading to a component of the disorder that is
      not based on any experimental data, and could be characterized as a guess. Real
      space refinement is less susceptible than other methods, but its application
      depends on the availability of very accurate experimental phases. A future
      challenge will be the collection of such data without resort to cryo-techniques,
      so that a physiologically relevant understanding can be achieved.

PMID- 11222307
TI  - pH-dependent local structure of ferricytochrome c studied by x-ray absorption
      spectroscopy.
AB  - We have studied, using x-ray absorption spectroscopy by synchrotron radiation,
      the native state of the horse heart cytochrome c (N), the HCl denatured state
      (U(1) at pH 2), the NaOH denatured state (U(2) at pH 12), the intermediate HCl
      induced state (A(1) at pH 0.5), and the intermediate NaCl induced state (A(2) at
      pH 2). Although many results concerning the native and denatured states of this
      protein have been published, a site-specific structure analysis of the denatured
      and intermediate solvent induced states has never been attempted before. Model
      systems and myoglobin in different states of coordination are compared with
      cytochrome c spectra to have insight into the protein site structure in our
      experimental conditions. New features are evidenced by our results: 1) x-ray
      absorption near edge structure (XANES) of the HCl intermediate state (A(1))
      presents typical structures of a pentacoordinate Fe(III) system, and 2) local
      site structures of the two intermediate states (A(1) and A(2)) are different.

PMID- 11222308
TI  - Thermal stability of collagen fibers in ethylene glycol.
AB  - The mechanism that renders collagen molecules more stable when precipitated as
      fibers than the same molecules in solution is controversial. According to the
      polymer-melting mechanism the presence of a solvent depresses the melting point
      of the polymer due to a thermodynamic mechanism resembling the depression of the
      freezing point of a solvent due to the presence of a solute. On the other hand,
      according to the polymer-in-a-box mechanism, the change in configurational
      entropy of the collagen molecule on denaturation is reduced by its confinement by
      surrounding molecules in the fiber. Both mechanisms predict an approximately
      linear increase in the reciprocal of the denaturation temperature with the volume
      fraction (epsilon) of solvent, but the polymer-melting mechanism predicts that
      the slope is inversely proportional to the molecular mass of the solvent (M),
      whereas the polymer-in-a-box mechanism predicts a slope that is independent of M.
      Differential scanning calorimetry was used to measure the denaturation
      temperature of collagen in different concentrations of ethylene glycol (M = 62)
      and the slope found to be (7.29 +/- 0.37) x 10(-4) K(-1), compared with (7.31 +/-
      0.42) x 10(-4) K(-1) for water (M = 18). This behavior was consistent with the
      polymer-in-a-box mechanism but conflicts with the polymer-melting mechanism.
      Calorimetry showed that the enthalpy of denaturation of collagen fibers in
      ethylene glycol was high, varied only slowly within the glycol volume fraction
      range 0.2 to 1, and fell rapidly at low epsilon. That this was caused by the
      disruption of a network of hydrogen-bonded glycol molecules surrounding the
      collagen is the most likely explanation.

PMID- 11222309
TI  - Effect of high pressure on the photochemical reaction center from Rhodobacter
      sphaeroides R26.1.
AB  - High-pressure studies on the photochemical reaction center from the
      photosynthetic bacterium Rhodobacter sphaeroides, strain R26.1, shows that, up to
      0.6 GPa, this carotenoid-less membrane protein does not loose its three
      dimensional structure at room temperature. However, as evidenced by Fourier
      transform preresonance Raman and electronic absorption spectra, between the
      atmospheric pressure and 0.2 GPa, the structure of the bacterial reaction center
      experiences a number of local reorganizations in the binding site of the primary
      electron donor. Above that value, the apparent compressibility of this membrane
      protein is inhomogeneous, being most noticeable in proximity to the
      bacteriopheophytin molecules. In this elevated pressure range, no more structural
      reorganization of the primary electron donor binding site can be observed.
      However, its electronic structure becomes dramatically perturbed, and the
      oscillator strength of its Q(y) electronic transition drops by nearly one order
      of magnitude. This effect is likely due to very small, pressure-induced changes
      in its dimeric structure.

PMID- 11222310
TI  - Time-resolved study of the inner space of lactose permease.
AB  - Pyranine (8-hydroxy pyrene-1,3,6-trisulfonate) is a commonly used photoacid that
      discharges a proton when excited to its first electronic singlet state. Follow-up
      of its dissociation kinetics reveals the physicochemical properties of its most
      immediate environment. At vanishing ionic strength the dye adsorbs to the
      Escherichia coli lactose permease with stoichiometry of 1:1 and an association
      constant of 2.5 x 10(5) M(-1). The reversal of the binding at high ionic strength
      and the lower pK value of the bound dye imply that positive charge(s) stabilize
      the dye in its site. The fluorescence decay curve of the bound dye was measured
      by time-correlated single photon counting and the measured transient was
      subjected to kinetic analysis based on the geminate recombination model. The
      analysis indicated that the binding domain is a cleft (between 9 and 17 A deep)
      characterized by low activity of water (a((water)) = 0.71), reduced diffusivity
      of protons, and enhanced electrostatic potential. The binding of pyranine and a
      substrate are not mutually exclusive; however, when the substrate is added, the
      dye-binding environment is better solvated. These properties, if attributed to
      the substrate-conducting pathway, may explain some of the forces operating on the
      substrate in the cavity. The reduced activities of the water strips the substrate
      from some of its solvation water molecules and replace them by direct interaction
      with the protein. In parallel, the lower dielectric constant enhances the binding
      of the proton to the protein, thus keeping a tight seal that prevents protons
      from diffusing.

PMID- 11222311
TI  - Ligand migration in human myoglobin: steric effects of isoleucine 107(G8) on O(2)
      and CO binding.
AB  - To investigate the ligand pathway in myoglobin, some mutant myoglobins, in which
      one of the amino acid residues constituting a putative ligand-docking site,
      Ile107, is replaced by Ala, Val, Leu, or Phe, were prepared and their structural
      and ligand binding properties were characterized. The kinetic barrier for the
      ligand entry to protein inside was lowered by decreasing the side-chain volume at
      position 107, indicating that the bulky side chain interferes with the formation
      of the activation state for the ligand migration and the free space near position
      107 would be filled with the ligand in the activation state. Another prominent
      effect of the reduced side-chain volume at position 107 is to stabilize the
      ligand-binding intermediate state. Because the stabilization can be ascribed to
      decrease of the positive enthalpy, the enlarged free space near position 107
      would relieve unfavorable steric interactions between the ligand and nearby amino
      acid residues. The side-chain volume at position 107, therefore, is crucial for
      the kinetic barrier for the ligand migration and free energy of the ligand
      binding intermediate state, which allows us to propose that some photodissociated
      O(2) moves toward position 107 to be trapped and then expelled to the solvent.

PMID- 11222312
TI  - Pressure-jump small-angle x-ray scattering detected kinetics of staphylococcal
      nuclease folding.
AB  - The kinetics of chain disruption and collapse of staphylococcal nuclease after
      positive or negative pressure jumps was monitored by real-time small-angle x-ray
      scattering under pressure. We used this method to probe the overall conformation
      of the protein by measuring its radius of gyration and pair-distance-distribution
      function p(r) which are sensitive to the spatial extent and shape of the
      particle. At all pressures and temperatures tested, the relaxation profiles were
      well described by a single exponential function. No fast collapse was observed,
      indicating that the rate limiting step for chain collapse is the same as that for
      secondary and tertiary structure formation. Whereas refolding at low pressures
      occurred in a few seconds, at high pressures the relaxation was quite slow,
      approximately 1 h, due to a large positive activation volume for the rate
      limiting step for chain collapse. A large increase in the system volume upon
      folding implies significant dehydration of the transition state and a high degree
      of similarity in terms of the packing density between the native and transition
      states in this system. This study of the time-dependence of the tertiary
      structure in pressure-induced folding/unfolding reactions demonstrates that novel
      information about the nature of protein folding transitions and transition states
      can be obtained from a combination of small-angle x-ray scattering using high
      intensity synchrotron radiation with the high pressure perturbation technique.

PMID- 11222313
TI  - Meanfield approach to the thermodynamics of protein-solvent systems with
      application to p53.
AB  - We present a meanfield theoretical approach for studying protein-solvent
      interactions. Starting with the partition function of the system, we develop a
      field theory by introducing densities for the different components of the system.
      At this point, protein-solvent interactions are introduced following the
      inhomogeneous Flory-Huggins model for polymers. Finally, we calculate the free
      energy in a meanfield approximation. We apply this method to study the stability
      of the tetramerization domain of the tumor suppressor protein p53 when subjected
      to site-directed mutagenesis. The four chains of this protein are held together
      by hydrophobic interactions, and some mutations can weaken this bond while
      preserving the secondary structure of the single protein chains. We find good
      qualitative agreement between our numerical results and experimental data, thus
      encouraging the use of this method as a guide in designing experiments.

PMID- 11222314
TI  - Fluorescent detection of Zn(2+)-rich vesicles with Zinquin: mechanism of action
      in lipid environments.
AB  - High concentrations of free Zn2+ ions are found in certain glutamatergic synaptic
      vesicles in the mammalian brain. These terminals can be visualized
      histochemically with quinoline sulfonamide compounds that form fluorescent
      complexes with Zn2+. The present study was undertaken to examine the interaction
      of the water-soluble quinoline sulfonamide probe, Zinquin (2-methyl-8-(toluene-p
      sulfonamido)-6-quinolyloxyacetic acid) with the complex heterogeneous cellular
      environment. Experiments on rat hippocampal and neocortical slices gave
      indications that Zinquin in its free acid form was able to diffuse across the
      plasma and synaptic vesicle membranes. Further experiments were undertaken on
      unilamellar liposomes to study the interaction of Zinquin and its metal complexes
      in membranes. These experiments confirmed that Zinquin is able to diffuse across
      lipid bilayers. Steady-state and time-resolved fluorimetric studies showed that
      Zinquin in aqueous solution mainly forms a 1:2 (metal:ligand) complex with small
      amounts of a 1:1 complex. Formation of the 1:1 complex was favored by the
      presence of lipid, suggesting that it partitions into membranes. Evidence is
      presented that Zinquin can act as a Zn(2+)-ionophore, exchanging Zn2+ for two
      protons. The presence of a pH gradient across vesicles traps the Zn(2+)-probe
      complex within the vesicles. Zinquin is useful as a qualitative probe for
      detecting the presence of vesicular Zn2+; however, its tendency to partition into
      membranes and to serve as an ionophore should be borne in mind.

PMID- 11222315
TI  - Optical and acoustical dynamics of microbubble contrast agents inside
      neutrophils.
AB  - Acoustically active microbubbles are used for contrast-enhanced ultrasound
      assessment of organ perfusion. In regions of inflammation, contrast agents are
      captured and phagocytosed by activated neutrophils adherent to the venular wall.
      Using direct optical observation with a high-speed camera and acoustical
      interrogation of individual bubbles and cells, we assessed the physical and
      acoustical responses of both phagocytosed and free microbubbles. Optical analysis
      of bubble radial oscillations during insonation demonstrated that phagocytosed
      microbubbles experience viscous damping within the cytoplasm and yet remain
      acoustically active and capable of large volumetric oscillations during an
      acoustic pulse. Fitting a modified version of the Rayleigh-Plesset equation that
      describes mechanical properties of thin shells to optical radius-time data of
      oscillating bubbles provided estimates of the apparent viscosity of the
      intracellular medium. Phagocytosed microbubbles experienced a viscous damping
      approximately sevenfold greater than free microbubbles. Acoustical comparison
      between free and phagocytosed microbubbles indicated that phagocytosed
      microbubbles produce an echo with a higher mean frequency than free microbubbles
      in response to a rarefaction-first single-cycle pulse. Moreover, this frequency
      increase is predicted using the modified Rayleigh-Plesset equation. We conclude
      that contrast-enhanced ultrasound can detect distinct acoustic signals from
      microbubbles inside of neutrophils and may provide a unique tool to identify
      activated neutrophils at sites of inflammation.

PMID- 11222316
TI  - Optical anisotropy in lipid bilayer membranes: coupled plasmon-waveguide
      resonance measurements of molecular orientation, polarizability, and shape.
AB  - The birefringence and linear dichroism of anisotropic thin films such as
      proteolipid membranes are related to molecular properties such as polarizability,
      shape, and orientation. Coupled plasmon-waveguide resonance (CPWR) spectroscopy
      is shown in the present work to provide a convenient means of evaluating these
      parameters in a single lipid bilayer. This is illustrated by using 1-10 mol % of
      an acyl chain chromophore-labeled phosphatidylcholine (PC) incorporated into a
      solid-supported PC bilayer deposited onto a hydrated silica surface. CPWR
      measurements were made of refractive index and extinction coefficient
      anisotropies with two exciting light wavelengths, one of which is absorbed by the
      chromophore and one of which is not. These results were used to calculate
      longitudinal and transverse molecular polarizabilities, the orientational order
      parameter and average angle between the longitudinal axis of the lipid molecule
      and the membrane normal, and the molecular shape factors of the lipid molecules.
      The values thereby obtained are in excellent agreement with parameters determined
      by other techniques, and provide a powerful tool for analyzing lipid-protein,
      protein-protein, and protein-ligand interactions in proteolipid films.

PMID- 11222317
TI  - Coherent scattering in multi-harmonic light microscopy.
AB  - By focusing a pulsed laser beam into a sample, harmonic up-conversion can be
      generated as well as multi-photon excited fluorescence. Whereas multi-photon
      excited fluorescence microscopy is well established, the use of multi-harmonic
      generation for three-dimensional image contrast is very recent. Both techniques
      can provide similar resolution and, for adequate radiating source density,
      comparable signal levels, allowing them to be combined in a single versatile
      instrument. However, harmonic generation differs fundamentally from fluorescence
      generation in that it is coherent and produces radiation patterns that are highly
      sensitive to phase. As such, multi-harmonic generation microscopy provides a
      unique window into molecular spatial organization that is inaccessible to
      fluorescence.

PMID- 11222318
TI  - Total internal reflection with fluorescence correlation spectroscopy: combined
      surface reaction and solution diffusion.
AB  - Total internal reflection with fluorescence correlation spectroscopy (TIR-FCS) is
      a method for measuring the surface association/dissociation rates and absolute
      densities of fluorescent molecules at the interface of solution and a planar
      substrate. This method can also report the apparent diffusion coefficient and
      absolute concentration of fluorescent molecules very close to the surface. An
      expression for the fluorescence fluctuation autocorrelation function in the
      absence of contributions from diffusion through the evanescent wave, in solution,
      has been published previously (N. L. Thompson, T. P. Burghardt, and D. Axelrod.
      1981, Biophys. J. 33:435-454). This work describes the nature of the TIR-FCS
      autocorrelation function when both surface association/dissociation kinetics and
      diffusion through the evanescent wave contribute to the fluorescence
      fluctuations. The fluorescence fluctuation autocorrelation function depends in
      general on the kinetic association and dissociation rate constants, the surface
      site density, the concentration of fluorescent molecules in solution, the
      solution diffusion coefficient, and the depth of the evanescent field. Both
      general and approximate expressions are presented.

PMID- 11222319
TI  - Time dependence of aggregation in crystallizing lysozyme solutions probed using
      NMR self-diffusion measurements.
AB  - The time dependence of aggregation in supersaturated lysozyme solutions was
      studied using pulsed-gradient spin-echo NMR diffusion measurements as a function
      of lysozyme concentration at pH 6.0 and 298 K in the presence of 0.5 M NaCl. The
      measurements provide estimates of the weight-averaged diffusion coefficient of
      the monomeric to intermediate molecular weight lysozyme species present in the
      solution (very large aggregates and crystals are excluded from the average due to
      the NMR relaxation-weighting effects inherent in the method). The results show
      that the average molecular weight of the various lysozyme aggregates changed with
      sigmoidal kinetics and that these kinetics were strongly influenced by the
      initial lysozyme concentration. The visualization of the time dependence of the
      protein aggregation afforded by this method provides a deeper understanding of
      how the crystallizing conditions (especially the initial protein concentration)
      are related to the resulting crystals.

PMID- 11222320
TI  - Spectroscopy on the B850 band of individual light-harvesting 2 complexes of
      Rhodopseudomonas acidophila. I. Experiments and Monte Carlo simulations.
AB  - The electronic structure of the circular aggregate of 18 bacteriochlorophyll a
      (BChl a) molecules responsible for the B850 absorption band of the light
      harvesting 2 (LH2) complex of the photosynthetic purple bacterium
      Rhodopseudomonas acidophila has been studied by measuring fluorescence-excitation
      spectra of individual complexes at 1.2 K. The spectra reveal several well
      resolved bands that are obscured in the single, broad B850 band observed in
      conventional absorption measurements on bulk samples. They are interpreted
      consistently in terms of the exciton model for the circular aggregate of BChl a
      molecules. From the energy separation between the different exciton transitions a
      reliable value of the intermolecular interaction is obtained. The spectra of the
      individual complexes allow for a distinction between the intra- and the
      intercomplex disorder. In addition to the random disorder, a regular modulation
      of the interaction has to be assumed to account for all the features of the
      observed spectra. This modulation has a C(2) symmetry, which strongly suggests a
      structural deformation of the ring into an ellipse.

PMID- 11222321
TI  - Spectroscopy on the B850 band of individual light-harvesting 2 complexes of
      Rhodopseudomonas acidophila. II. Exciton states of an elliptically deformed ring
      aggregate.
AB  - Spectroscopy of individual light-harvesting 2 complexes from purple
      photosynthetic bacteria revealed a deformation of the circular complex into C(2)
      symmetry. The present work relates the geometry of the deformed aggregate to its
      spectroscopic properties. Different models of elliptical deformation are
      discussed and compared with the experimental findings. It is shown that the model
      with smaller interpigment distances, where the curvature of the ellipse is small,
      provides the best agreement with fluorescence excitation spectra of individual
      complexes.

PMID- 11222322
TI  - World blindness--no end in sight.

PMID- 11222323
TI  - Cataract surgery in young children.

PMID- 11222324
TI  - Gene therapy in hereditary retinal degeneration and the tower of Babel.

PMID- 11222326
TI  - Screening and surveillance for ophthalmic disorders and visual deficits in
      children in the United Kingdom.

PMID- 11222327
TI  - World blindness: a 21st century perspective.

PMID- 11222328
TI  - Results of cataract surgery in young children in east Africa.
AB  - BACKGROUND: Cataract is the leading cause of blindness in children in east
      Africa. The results of surgery are poor, partly because of inadequate correction
      of aphakia. METHODS: A retrospective survey of 118 eyes in 71 children with
      bilateral cataract. All eyes had implantation of an IOL at the time of cataract
      surgery. The average age at surgery was 3.5 years. 28 patients(39%) were less
      than 2 years old at the time of surgery on their first eye. RESULTS:
      Preoperatively, 75.4% of eyes and 76.1% of patients were blind. A follow up of at
      least 3 months was available in 91 (77.1%) eyes. In these eyes, 44% had a latest
      corrected vision of 6/18 or better and 91.2% had a latest corrected vision of
      6/60 or better. Eyes with zonular cataract, and eyes operated after the age of 2
      years were more likely to obtain a vision of 6/18 or better. 3.3% of eyes and
      1.8% of patients had an acuity of less than 3/60. Nystagmus was present in 42.3%
      of patients before surgery. In those patients followed up for a minimum of 6
      months, 10.2% still had nystagmus. The most frequent complication was severe
      fibrinous uveitis, which occurred in 36 (30.5%) eyes. 62 (52.5%) eyes had a
      posterior capsulotomy at the time of cataract extraction. Of the remaining 56
      eyes, 20 (35.7%) had so far required a posterior capsulotomy. The leading cause
      of poor visual outcome was amblyopia. Two patients developed severe complications
      related to the intraocular lens. CONCLUSIONS: Insertion of a lens implant at the
      time of cataract extraction appears to be well tolerated in the short term, and
      may offer significant advantages in an African setting.

PMID- 11222329
TI  - Screening human donor corneas during organ culture for the presence of guttae.
AB  - AIMS: To detect the presence of guttae by means of light microscopy during organ
      culture and to evaluate the influence of the presence of guttae in the donor
      tissue on transplantation outcome. METHODS: Donor corneas were investigated for
      the presence of guttae by means of light microscopy at the end of organ culture.
      Recipient corneal buttons from patients with severe Fuchs' dystrophy and donor
      corneas with advanced guttae were first studied by light microscopy and
      subsequently by transmission electron microscopy. Lastly, 168 consecutive donor
      corneas were evaluated for the presence of guttae and issued for transplantation.
      RESULTS: Corneal specimens with Fuchs' dystrophy displayed numerous round highly
      reflecting guttae at the level of the corneal endothelium. Donor corneas with
      advanced guttae showed less numerous guttae. Among 168 organ cultured donor
      corneas issued for transplantation, low density guttae were found in 43 (25.6%)
      corneas. The endothelial cell density and figure coefficient were significantly
      lower and organ culture time was significantly higher in the cornea guttata group
      than in the control group. The presence of grouped guttae significantly decreased
      the adjusted graft survival. The incidence of postoperative stage 3 cornea
      guttata was significantly higher when grouped guttae were found (5/6) than when
      no guttae or scattered guttae were found (8/101). CONCLUSION: Cornea guttata can
      be detected during organ culture by means of light microscopy. It is associated
      with a decrease in endothelial cell figure coefficient and cell density. The
      presence of grouped guttae is associated with poorer graft survival and more
      frequent stage 3 cornea guttata in the graft after transplantation.

PMID- 11222330
TI  - Persistence of acanthamoeba antigen following acanthamoeba keratitis.
AB  - AIM: To investigate the hypothesis that persistent corneal and scleral
      inflammation following acanthamoeba keratitis is not always caused by active
      amoebic infection but can be due to persisting acanthamoebic antigens METHODS: 24
      lamellar corneal biopsy and penetrating keratoplasty specimens were obtained from
      14 consecutive patients at various stages of their disease and divided for
      microscopy and culture. Histological sections were immunostained and screened for
      the presence of Acanthamoeba cysts by light microscopy. Cultures were carried out
      using partly homogenised tissues on non-nutrient agar seeded with E coli.
      Clinical data were obtained retrospectively from the case notes of these
      patients. RESULTS: Of the 24 specimens, 20 were obtained from eyes that were
      clinically inflamed at the time of surgery. Acanthamoeba cysts were present in 16
      (80%) of these 20 specimens, while only five (25%) were culture positive.
      Acanthamoeba cysts were found to persist for up to 31 months after antiamoebic
      treatment. CONCLUSION: These findings support the hypothesis that Acanthamoeba
      cysts can remain in corneal tissue for an extended period of time following
      acanthamoeba keratitis and may cause persistent corneal and scleral inflammation
      in the absence of active amoebic infection. In view of these findings, prolonged
      intensive antiamoebic therapy may be inappropriate when the inflammation is due
      to retained antigen rather than to viable organisms

PMID- 11222331
TI  - Immunogenetics and clinical phenotype of sympathetic ophthalmia in British and
      Irish patients.
AB  - BACKGROUND/AIMS: Sympathetic ophthalmia (SO) is a classic example of autoimmune
      disease where human leucocyte antigen (HLA) genomic associations could provide
      further understanding of mechanisms of disease. This study sought to assess HLA
      genetic polymorphism in British and Irish patients with SO, and to assess whether
      HLA gene variants are associated with clinical phenotype or disease severity.
      METHODS: High resolution DNA based HLA typing using polymerase chain reaction
      sequence specific primers was performed in 27 patients with SO and 51 matched
      healthy controls. Clinical phenotype and markers of disease severity were
      determined prospectively in 17 newly diagnosed patients and from medical record
      review and repeat clinical examination in 10 previously diagnosed patients.
      RESULTS: HLA-Cw*03 (p=0.008), DRB1*04 (p=0.017), and DQA1*03 (p=0.014) were
      significantly associated with SO. For class II alleles at higher resolution, only
      HLA-DRB1*0404 (relative risk (RR) = 5.6, p = 0.045) was significantly associated
      with SO. The highest relative risk for any of the associated haplotypes was with
      HLA-DRB1*0404-DQA1*0301 (RR=10.9, p=0.019). Patients with the DRB1*04-DQA1*03
      associated haplotype were significantly more likely to develop SO earlier, with
      fewer inciting ocular trauma events, and to require more systemic steroid therapy
      to control inflammatory activity. CONCLUSIONS: Sympathetic ophthalmia is
      associated with HLA-DRB1*04 and DQA1*03 genotypes in white patients, similar to
      Japanese patients. Differences in DRB1*04 gene variant associations (-0404 in
      Britain and Ireland and -0405 in Japan) may have implications for HLA peptide
      binding in disease initiation. The DRB1*04-DQA1*03 haplotype is a marker of
      increased SO susceptibility and severity, as in Vogt-Koyanagi-Harada disease,
      which also has similar clinicopathological and HLA associations.

PMID- 11222332
TI  - Reduced amplitude and delayed latency in foveal response of multifocal
      electroretinogram in early age related macular degeneration.
AB  - AIM: To explore the use of multifocal electroretinograms (MERG) in detecting
      early changes in age related macular degeneration (AMD). METHOD: 15 pre-AMD or
      early AMD eyes showing retinal drusen or irregular fundus pigmentation with
      window defects by fluorescein angiography (FA) and mildly decreased visual acuity
      were examined and compared with their asymptomatic fellow eyes. 20 age matched
      normal eyes were included as controls. MERG was recorded by a Veris system
      (version 3.0) using a 103 hexagon stimulus and 218 second total recording time
      per eye. The first order kernel was used to calculate amplitudes and latencies in
      three configurations: the nasal and the temporal areas, the superior and the
      inferior areas, and six concentric rings centred on the fovea. RESULTS: There
      were no significant differences in the amplitudes and the latencies between the
      different regions (nasal versus temporal and superior versus inferior) of the
      retina as well as between the different groups of eyes (normal, pre-AMD or early
      AMD, and the asymptomatic fellow eyes) in each region. Using the concentric
      configuration, the foveal amplitude of pre-AMD or early AMD eyes was
      significantly suppressed when compared with the age matched control group and
      their average latency was longer in the fovea than in outer rings and
      significantly prolonged when compared with the normal control group. Similar
      changes in amplitude and latency were also observed in the asymptomatic fellow
      eyes. CONCLUSION: Significant abnormality in the foveal amplitude and the foveal
      latency of MERG could be detected in pre-AMD or early AMD eyes as well as their
      asymptomatic contralateral eyes, suggesting MERG as a sensitive tool in detecting
      early foveal abnormalities in AMD.

PMID- 11222333
TI  - Distant cancer effects on standardised testing of peripheral vision.
AB  - BACKGROUND: Profound central-retinal visual losses have been a major presenting
      factor reported in cancer and melanoma associated retinopathies (CAR, MAR).
      However, it is well established that standardised tests of peripheral retinal
      function are often the most sensitive detectors of early eye disease. This is a
      preliminary investigation of the responsiveness of the peripheral retina to
      "distant" (non-eye or CNS) cancers using easily obtained standardised tests.
      METHODS: The design is a single blind study where test results are compared with
      published norms and a small age matched control group. Of 120 ambulatory cancer
      outpatients who were interviewed at routine follow up examinations, 111
      volunteered and admitted a range of mild visual changes. 25 cancer patients
      completed all tests of peripheral vision function and a clinical screening. There
      were seven control subjects of the same age range. RESULTS: 98% (49 of 50) of
      eyes from the patient cohort were judged clinically normal following examinations
      which emphasised the central retina, fundus appearance, and static fields. On
      testing which emphasised the visual periphery, 46 (92%) eyes showed one or more
      quantitative abnormalities >2 SD from the age adjusted norm means. These
      abnormalities clustered mainly about dark adaptation (rod cell) sensitivity (31,
      62% of measured sites), the blue sensitive retinal cells (17, 34% of measured
      eyes), and the oscillatory component (OP) of the electroretinogram (23, 46% of
      measured eyes). One control eye (7%) showed a significant dark adaptation
      abnormality and ERG reduction. There was no identifiable interaction between
      chemotherapy mode and the cancer associated retinal deficits (CARD). Antiretinal
      antibodies were found in sera from most patients and controls. CONCLUSION: CARD
      is common in the retinal periphery of many cancer patients, and is distinct from
      rare CAR, MAR central-retinal responses. CARD has numerous potential clinical
      uses which justify expanded research with more defined large samples.

PMID- 11222334
TI  - Scanning laser ophthalmoscopy of the optic nerve head in exfoliation glaucoma and
      ocular hypertension with exfoliation syndrome.
AB  - AIMS: To study the relation between optic nerve head topography (Heidelberg
      retina tomograph, HRT) and disc area, visual field index mean defect (MD), and
      intraocular pressure (IOP), and to see whether change in HRT parameters is
      associated with change in MD in a prospective follow up. METHODS: 80 consecutive
      patients (69 patients with exfoliation glaucoma and 11 with ocular hypertension
      combined with exfoliation syndrome) were examined before IOP reducing
      intervention and prospectively followed every 6 months for 2 years. RESULTS: At
      the entry point, multiple regression analysis showed significant linear
      association between MD and all HRT parameters, when controlling for disc area.
      Disc area showed significant association with cup area, cup/disc area ratio, rim
      area, cup volume, and mean RNFL thickness. Six months after intervention IOP had
      decreased significantly. Reversible changes in cup area, cup/disc area ratio, rim
      area, cup volume, rim volume, mean cup depth, and maximum cup depth were
      associated with decrease in IOP. During the follow up period from 6 month to 2
      years, IOP did not change significantly, and MD was used as a measure of
      progression of glaucoma. During this period, only cup shape measure among HRT
      parameters showed significant association with subsequent change in MD.
      CONCLUSION: Disc area should be taken into account when using HRT to compare
      patients. Any effect of change in IOP should be also taken into account when
      using HRT in follow up. Cup shape measure is a promising indicator of progression
      of glaucomatous damage.

PMID- 11222335
TI  - New neuroretinal rim blood flow evaluation method combining Heidelberg retina
      flowmetry and tomography.
AB  - AIM: Accurate Heidelberg retina flowmeter (HRF) measurements require correct
      manual setting of the HRF photodetector sensitivity. The neuroretinal rim
      produces a weak signal relative to the peripapillary retina. A newly developed
      HRF alignment and sensitivity protocol, capable of accurate rim measurement, was
      investigated. METHODS: 18 eyes of nine healthy volunteers were examined by HRF.
      Three images of each eye were taken using three different imaging methods. Method
      1: a conventional image (optic nerve head centred image with photodetector
      sensitivity optimised for the strong signal from the peripapillary retina);
      method 2: the setting of method 1 with photodetector sensitivity optimised for
      the weak signal from the rim; and method 3: the setting of method 2 with the
      temporal rim margin tangent to the lateral image border to remove the
      overpowering signal from the temporal peripapillary retina. The neuroretinal rim
      was defined by the Heidelberg retina tomograph (HRT). Blood flow and reflectivity
      values (DC component) in the rim area were compared for the three methods using
      pointwise analysis. Coefficients of variation of repeated measurements in 12
      subjects have been calculated for method 3. RESULTS: The neuroretinal rim area
      measured by method 1 had a significantly lower brightness compared with method 2
      and 3 (p=0.0002 and p=0.0002, respectively). Method 2 provided proper sensitivity
      for the weak signals of the rim area based on rim tissue DC values; however, this
      sensitivity setting was too high for the strong signal from the peripapillary
      retina. Method 3 avoided the strong peripapillary signal with the proper signal
      from the rim and provided significantly higher flow values of the rim area at 75
      and 90 percentile pixels (p=0.0065 and p=0.0038 respectively) compared with
      method 2. Interobserver repeatability ranged from 16.85% to 21.96% for the
      different parameters. CONCLUSIONS: Method 3 provides an accurate and reproducible
      flow measurement of the neuroretinal rim area through proper sensitivity for the
      weak rim signal, alignment, and removal of the strong temporal signal from the
      image. This new method is recommended to improve accuracy of blood flow
      measurement in the neuroretinal rim.

PMID- 11222336
TI  - Intensive occlusion therapy for amblyopia.
AB  - AIM: To study the effects of supervised inpatient occlusion treatment for
      amblyopia in children who had failed to respond to outpatient treatment. METHODS:
      A retrospective study of 39 children admitted to a paediatric ophthalmic ward for
      5 days of supervised intensive occlusion therapy having previously failed to
      respond to outpatient occlusion. Visual acuity of amblyopic and fellow eyes was
      recorded at each clinic visit before admission, daily during admission, and at
      each outpatient visit after discharge. RESULTS: There was no significant overall
      improvement in visual acuity during a mean of 9 months of attempted outpatient
      occlusion before admission. During the 5 days of admission 26 children (67%)
      gained at least one line of acuity in their amblyopic eye and five (13%) gained
      three or more lines (mean gain 1.03 Snellen lines). The acuities of both the
      amblyopic and fellow eyes subsequently improved with continuing part time
      patching as an outpatient, including in nine of the children who did not respond
      during admission. At the last recorded visit, at a median time of 14 months after
      discharge, 13 (33%) of the patients had an acuity of at least 6/12 in their
      amblyopic eye. CONCLUSIONS: The acuity of amblyopic eyes did not improve without
      effective treatment. Subsequent supervised inpatient occlusion therapy was
      effective in the majority of the children.

PMID- 11222337
TI  - Value of nasal endoscopy and probing in the diagnosis and management of children
      with congenital epiphora.
AB  - BACKGROUND: Congenital nasolacrimal obstruction is usually the result of failure
      of canalisation of the distal end of the nasolacrimal duct. The most common
      outcome is spontaneous resolution, but some children do require surgical
      treatment by probing. Probing is a blind procedure with a recognised failure
      rate. METHODS: In 52 lacrimal systems of 40 children nasal endoscopy was combined
      with a "stepwise" systematic probing in an attempt to improve the outcome and
      reduce the number of repeat procedures. RESULTS: Combined nasal endoscopy and
      probing improved the understanding of outflow obstruction in young children. The
      success of the procedure depended upon the level of the obstruction within the
      outflow system. Formation of a false passage was seen in six cases (15%). The
      probe was rerouted under direct visualisation in these cases to form a
      functioning passage. Reasons for failure were identified in those who did not
      have a successful outcome and only one repeat procedure was required. CONCLUSION:
      Using nasal endoscopy the area of lacrimal outflow obstruction at the lower end
      of the nasolacrimal duct can be observed directly and it is possible to guide the
      progress of probing under direct vision. This gives better information about the
      nature of the obstruction, minimises the formation of false passages, and allows
      a wider range of treatment options under a single anaesthetic.

PMID- 11222338
TI  - The assessment of lens opacities in clinical practice: results of a national
      survey.
AB  - AIM: To investigate the examination of lens opacities in routine ophthalmic
      clinical practice. METHOD: A questionnaire survey was mailed to 703 consultant
      ophthalmologists in the UK. The surgeons were asked which lens feature(s) they
      assessed in their clinics when deciding whether to offer cataract surgery.
      RESULTS: 489 replies were received. A broad range of lens opacities was assessed,
      with differences between surgeons for some opacities with high prevalences in the
      population, particularly cortical opacities. Many (74% of 467) surgeons assessed
      one or more lens opacities (anterior subcapsular cataract, vacuoles, water
      clefts, coronary flakes, focal dots, retrodots, fibre folds) which may be
      visually important but which have received relatively little attention by
      researchers. CONCLUSIONS: Some classes of lens opacity which are traditionally
      measured by researchers may be ignored in clinical practice and opacities which
      are traditionally ignored by some researchers are regarded as clinically
      important by a substantial number of surgeons.

PMID- 11222339
TI  - Vision impairment predicts 5 year mortality.
AB  - AIM: To describe predictors of mortality in the 5 year follow up of the Melbourne
      Visual Impairment Project (VIP) cohort. METHODS: The Melbourne VIP was a
      population based study of the distribution and determinants of age related eye
      disease in a cluster random sample of Melbourne residents aged 40 years and
      older. Baseline examinations were conducted between 1992 and 1994. In 1997, 5
      year follow up examinations of the original cohort commenced. Causes of death
      were obtained from the National Death Index for all reported deaths. RESULTS: Of
      the original 3271 participants, 231 (7.1%) were reported to have died in the
      intervening 5 years. Of the remaining 3040 participants eligible to return for
      follow up examinations, 2594 (85% of eligible) did participate, 51 (2%) had moved
      interstate or overseas, 83 (3%) could not be traced, and 312 (10%) refused to
      participate. Best corrected visual acuity <6/12 (OR=2.34) was associated with a
      significantly increased risk of mortality, as were increasing age (OR=1.09), male
      sex (OR=1.62), increased duration of cigarette smoking (OR=2.06 for smoking >30
      years), increased duration of hypertension (OR=1.51 for duration >10 years), and
      arthritis (OR=1.42). CONCLUSIONS: Even mild visual impairment increases the risk
      of death more than twofold. Further research is needed to determine why decreased
      visual acuity is associated with increased risk of mortality.

PMID- 11222340
TI  - Utility values associated with blindness in an adult population.
AB  - AIM: To ascertain utility values associated with varying degrees of legal
      blindness. METHODS: A cross sectional study on three group of patients. There
      were: (1) 15 patients with complete absence of vision (no light perception) in at
      least one eye who were asked to assume a scenario of no light perception in the
      second eye as well, (2) 17 patients with light perception to counting fingers in
      the better seeing eye, and (3) 33 patients with 20/200-20/400 vision in the
      better seeing eye. Utility values were measured using the time trade-off and
      standard gamble methods in each of the three groups. RESULTS: The mean time trade
      off utility value for the no light perception group with the theoretical scenario
      of bilateral absence of light perception was 0.26 (95% CI, 0.19-0.33). The mean
      utility value for the light perception to counting fingers group was 0.47 (95%
      CI, 0.33-0.61), and the mean utility value for the 20/200-20/400 group was 0.65
      (95% CI, 0.58-0.72). Thus, patients with no light perception in one eye, who were
      presented with the same scenario in the second eye as well, were willing to trade
      almost 3 out of every 4 years of remaining life in return for perfect vision in
      each eye. Those with light perception to counting fingers would trade
      approximately 1 of 2 remaining years and those with 20/200-20/400 would trade
      approximately 1 of 3 remaining years. CONCLUSIONS: There is a wide range of
      utility values associated with legal blindness. The utility value decreases
      dramatically with perceived total loss of vision (absence of light perception in
      each eye), compared with counting fingers to light perception vision, indicating
      that the preservation of even small amounts of vision in patients with legal
      blindness is critically important to their wellbeing and functioning in life.

PMID- 11222341
TI  - The effect of scleral search coil lens wear on the eye.
AB  - BACKGROUND/AIM: Scleral search coils are used to measure eye movements. A recent
      abstract suggests that the coil can affect the eye by decreasing visual acuity,
      increasing intraocular pressure, and damaging the corneal and conjunctival
      surface. Such findings, if repeated in all subjects, would cast doubt on the
      credibility of the search coil as a reliable investigative technique. The aim of
      this study was to reassess the effect of the scleral search coil on visual
      function. METHODS: Six volunteer subjects were selected to undergo coil wear and
      baseline measurements were taken of logMAR visual acuity, non-contact tonometry,
      keratometry, and slit lamp examination. Four drops of 0.4% benoxinate
      hydrochloride were instilled before insertion of the lens by an experienced
      clinician. The lens then remained on the eye for 30 minutes. Measurements of the
      four ocular health parameters were repeated after 15 and 30 minutes of lens wear.
      The lens was then removed and the health of the eye reassessed. RESULTS: No
      obvious pattern of change was found in logMAR visual acuity, keratometry, or
      intraocular pressure. The lens did produce changes to the conjunctival and
      corneal surfaces, but this was not considered clinically significant. CONCLUSION:
      Search coils do not appear to cause any significant effects on visual function.
      However, thorough prescreening of subjects and post-wear checks should be carried
      out on all coil wearers to ensure no adverse effects have been caused.

PMID- 11222342
TI  - A comparison of cyst age and assay method of the efficacy of contact lens
      disinfectants against Acanthamoeba.
AB  - AIMS: (i) To determine effect of Acanthamoeba cyst age, method of production, and
      (ii) to assay technique on the efficacy of multipurpose solutions (MPS) and
      hydrogen peroxide based contact lens disinfectants. (iii) To establish if MPS can
      remove mature cysts from contact lenses according to the ISO/DIS 14729 regimen
      test for microbe removal. METHODS: Immature and mature cysts of A polyphaga were
      tested against the MPS Opti-Free express and the hydrogen peroxide based
      solutions Oxysept 1Step and Oxysept 1 using two assay methods. Simulated patient
      regimen testing was performed with the Opti-Free express and Complete using
      mature cysts inoculated on to group I or group IV lenses. RESULTS: Immature cysts
      were sensitive to disinfection by all solutions. No killing was observed with
      mature cysts with Opti-Free express, while immature cysts yielded a 1-2 log
      reduction in viability. Oxysept 1Step gave a 1.1 (SD 0.3) log reduction in mature
      cysts after 6 hours. Oxysept 1 gave a 2.4 (0.3) log reduction in mature cysts
      after 4 hours and a 3.8 (0.5) log reduction after 6 hours. Patient regimen
      testing using Opti-Free express and Complete resulted in no recovery of viable
      mature cysts from the contact lenses or from the soaking solutions. CONCLUSION:
      Cyst age but not method of production used in this study influences the efficacy
      of contact lens disinfectants against Acanthamoeba. MPS are effective in removing
      cysts from contact lens surfaces and may have a role in the prevention of
      acanthamoeba keratitis.

PMID- 11222343
TI  - An immune response after intraocular administration of an adenoviral vector
      containing a beta galactosidase reporter gene slows retinal degeneration in the
      rd mouse.
AB  - BACKGROUND/AIMS: Retinal degenerations are a leading cause of blindness for which
      there are currently no effective treatments. This has stimulated interest in the
      investigation of gene therapy strategies for these diseases in a variety of
      animal models. A number of attempts have been made to prevent photoreceptor loss
      in the rd mouse model of retinal degeneration using adenoviral vectors containing
      either a copy of the missing functional gene or a gene encoding either a
      neurotrophic factor or an antiapoptotic factor. The authors have previously
      demonstrated that intraocular administration of an adenoviral vector containing a
      beta galactosidase gene (AV.LacZ) results in an immune response to viral gene
      products and beta galactosidase. Here the effect of the immune response on
      retinal degeneration is examined. METHODS: Juvenile rd mice were injected
      intravitreally with AV.LacZ and a proportion were depleted of either CD4+ or CD8+
      T cells or both. Control animals were injected with PBS. The mice were sacrificed
      10 and 20 days post-injection and their eyes embedded in paraffin wax and
      sectioned. RESULTS: 10 days after intravitreal injection of AV.LacZ, the outer
      nuclear layer contains an average of 2.5 rows compared with 1.5 in PBS injected
      animals (p<0.005). The protective effect of AV.LacZ is negated by immune
      suppression and does not extend beyond 20 days. CONCLUSION: An immune response to
      vector and transgene products is able to slow degeneration in the rd mouse. This
      phenomenon should be taken into account when analysing the degeneration in the rd
      mouse following gene transfer.

PMID- 11222344
TI  - Effects of amniotic membrane on epithelial wound healing and stromal remodelling
      after excimer laser keratectomy in rabbit cornea.
AB  - AIMS: To investigate if the amniotic membrane (AM) promotes epithelial migration
      while inhibiting stromal remodelling associated with corneal haze after excimer
      laser keratectomy. METHODS: A wound 150 microm in depth and 6.0 mm in diameter
      was produced in 40 rabbits using an excimer laser. One eye was randomly chosen to
      be covered by the AM while the other eye served as a control. Epithelial wound
      healing was evaluated, together with any morphological changes of the anterior
      stroma connected with corneal haze. These morphological changes were
      histopathologically analysed using dichlortriazinyl aminofluorescein (DTAF),
      Masson trichrome staining, and an image analyser. RESULTS: The AM group had a
      short latent phase followed by fast epithelial healing (p<0.001) during the early
      wound healing period and a significant decrease in the inflammatory response,
      together with a smaller change in the number of keratocytes than the control
      group. The mean thickness of the regenerated stroma was significantly thinner in
      the AM group than in the control group at 8 weeks (p<0.0001). The AM group had a
      more regular architecture of regenerated stromal lamella at 8 weeks and
      significantly less haze after 4 weeks than the control group (p<0.05).
      CONCLUSION: Use of the AM as a dressing on a corneal wound created by excimer
      laser surgery, in which severe haze is expected, may induce rapid epithelial
      healing with less inflammatory response. The AM may inhibit the irregular
      synthesis of stromal collagen that is associated with corneal haze.

PMID- 11222345
TI  - Vascular patterns in pterygium and conjunctival autografting: a pilot study using
      indocyanine green anterior segment angiography.
AB  - AIMS: To characterise the vasculature of pterygium using indocyanine green (ICG)
      anterior segment angiography and to demonstrate the pattern of revascularisation
      following conjunctival autografting. METHODS: ICG anterior segment angiography
      was performed on nine patients with pterygium. Angiography was repeated at 1-2
      weeks and 2 months following conjunctival autografting in these patients.
      RESULTS: Angiography showed a single feeder vessel originating from the anterior
      conjunctival circulation in six cases (66.7%). This vessel branched to form the
      radial vessels of the pterygium. Following conjunctival autografting, reperfusion
      of the vessels in the conjunctival autograft was demonstrable as early as 1 week
      postoperatively from the episcleral bed. At 2 months postoperatively, the graft
      appeared well perfused with mild leakage demonstrable at the edges of the graft.
      CONCLUSIONS: A single feeder vessel from the anterior conjunctival circulation
      branches to form the radial vessels in pterygium. Reperfusion of conjunctival
      autografts occurs as early as 1 week postoperatively from the episcleral bed.

PMID- 11222346
TI  - Incidence of blindness due to diabetic eye disease in Fife 1990-9.
AB  - AIMS: In the light of goals for reducing blindness due to diabetes, published in
      the St Vincent Declaration, 1989, the aim of this study was to find the incidence
      and prevalence of blindness in the diabetic population of Fife. METHODS: All
      blind registrations for the period 1990-9 were studied. Those with diabetes as
      the first or main diagnosis were included as new diabetic blind. The prevalence
      of diabetes was studied in a large sample population and extrapolated to the
      estimated population of Fife. RESULTS: The incidence of blindness due to diabetes
      was 64 (SD 24, 95% CI 49-79) per 100 000 diabetic population/year. The point
      prevalence of blindness due to diabetes on 31 December 1999 was 210 per 100 000
      diabetic population. CONCLUSION: The incidence of blindness due to diabetes, in a
      diabetic population, is now known. Without this benchmark it is impossible to
      assess the implementation of the St Vincent Declaration.

PMID- 11222347
TI  - Ocular significance of intraventricular haemorrhage in premature infants.
AB  - AIM: To document ocular outcome in premature infants with intraventricular
      haemorrhages (IVH). METHODS: 68 preterm infants with IVH were examined. RESULTS:
      Mean gestational age was 28.1 weeks (range 24-35). Mean birth weight was 1045.9 g
      (630-2240). Mean follow up was 54.6 months (6-150). IVH is graded from 1 to 4
      based on the severity of haemorrhages. The incidence of ocular abnormalities was
      compared between low grade IVH (grade 1 and 2) and high grade IVH (grade 3 and
      4). Of the 68 infants with IVH, ROP occurred in 33 infants (48.5%); 13 (43.3%)
      had low grade IVH; 20 (52.6%) had high grade IVH. Strabismus developed in 30
      infants (44.1%); 14 (46.6%) had low grade IVH; 16 (42.1%) had high grade IVH.
      Infants with high grade IVH were at significant greater risk than infants with
      low grade IVH for the development of optic atrophy (31.5% v 16.6%), hydrocephalus
      (57.8% v 10%). CONCLUSION: This study highlights the serious significance of all
      grades of IVH with the higher incidence of optic atrophy and hydrocephalus with
      high grade IVH.

PMID- 11222348
TI  - Clinical comparison of frequency doubling technology perimetry and Humphrey
      perimetry.
AB  - AIM: To determine the number of missed points on frequency doubling technology
      (FDT) perimetry that optimise the sensitivity and specificity of the test and to
      determine the topographical accuracy of the test in a clinical setting. METHODS:
      In a prospective study, the perimetric data from 99 patients who underwent both
      FDT perimetry in the screening mode and Humphrey 24-2 (H24-2) were used to
      determine the sensitivity and specificity of the FDT perimetry compared with the
      full threshold H24-2 as the gold standard. RESULTS: Missed points on the FDT
      perimetry correlated with both the mean deviation and the corrected pattern
      standard deviation on the Humphrey perimetry. A score assigned to abnormal points
      on the FDT perimetry and the Humphrey total deviation plot showed a significant
      correlation for both the location and the depth of the defect. In comparing the
      Humphrey hemifield test with the FDT perimetry results, if at least one missed
      point on the frequency doubling test was considered as abnormal then the overall
      sensitivity of the test was 78.1% and the specificity was 89.1%. CONCLUSION: FDT
      perimetry in the screening mode performed in a clinical setting was highly
      specific, exhibited reasonable sensitivity, and accurately determined the
      location and depth of scotomas when compared with the full threshold Humphrey 24
      2.

PMID- 11222349
TI  - Rapid onset of ptosis indicates accurate intraconal placement during retrobulbar
      anaesthetic injection.
AB  - BACKGROUND: Anecdotal evidence has previously suggested that retrobulbar local
      anaesthetic (LA) injection is accompanied by the rapid onset of ptosis. Here the
      validity of this potentially valuable sign is tested. METHODS: 25 patients
      received a retrobulbar injection and the times for development of ptosis and
      akinesia in other extraocular muscle groups were recorded and compared. The
      effects of retrobulbar injections were also studied on posterior orbital
      structures in 10 patients using low frequency ultrasound. RESULTS: The mean time
      of onset of ptosis was 4.76 seconds, an order of magnitude less than times
      recorded for akinesia in other muscle groups. Ultrasonography revealed a
      significant distension of the extraocular muscle cone during retrobulbar
      injection. CONCLUSION: Ptosis develops significantly more rapidly than other
      motor effects in retrobulbar anaesthesia and can therefore be taken as an
      indicator of accurate intraconal placement. Retrobulbar injection is associated
      with significant distension of the extraocular muscle cone.

PMID- 11222351
TI  - Anterior uveitis and its relation to stress.

PMID- 11222350
TI  - The absence of diabetic retinopathy in patients with retinitis pigmentosa:
      implications for pathophysiology and possible treatment.

PMID- 11222356
TI  - Fas-L up-regulation by highly malignant myeloma plasma cells: role in the
      pathogenesis of anemia and disease progression.
AB  - Highly malignant myeloma cells up-regulate their Fas-ligand (Fas-L) to escape
      immune surveillance by Fas(+) cytotoxic cells. Here it is demonstrated that this
      abnormality is involved in the pathogenesis of the severe anemia associated with
      progression of multiple myeloma (MM). By measuring Fas and Fas-L in plasma cells
      and erythroblasts from 19 MM patients and 5 with monoclonal gammopathies of
      undetermined significance (MGUS), it was found that both Fas-L(+) myeloma cells
      and Fas(+) erythroid progenitors were significantly increased in patients with
      stage III MM whose erythroblasts, cultured in the presence of autologous plasma
      cells or their supernatant, underwent prompt apoptosis as evaluated by propidium
      iodide staining, the TUNEL assay, and detection of the APO2.7-reactive
      mitochondrial antigen. Flow cytometry of fresh erythroblasts revealed a
      considerable expression of the caspases CPP32 and FLICE in both their
      constitutive proenzymatic forms and in cleaved subunits. By contrast, their
      intracytoplasmic expression was defective in patients with inactive disease and
      MGUS controls. The evidence that Fas-L(+) myeloma clones directly prime
      erythroblast apoptosis in vivo was further supported by the occurrence of
      fluorescein isothiocyanate-TUNEL(+) erythroblasts juxtaposed to myeloma cells in
      bone marrow smears. These results strongly suggest that the deregulated apoptosis
      in myeloma clones plays an active role in the progressive destruction of the
      erythroid matrix by a cytotoxic mechanism based on up-regulation of Fas-L.

PMID- 11222357
TI  - Frequent monitoring of Epstein-Barr virus DNA load in unfractionated whole blood
      is essential for early detection of posttransplant lymphoproliferative disease in
      high-risk patients.
AB  - Posttransplant lymphoproliferative disease (PTLD) is a frequent and severe
      Epstein-Barr virus (EBV)-associated complication in transplantation recipients
      that is caused by iatrogenic suppression of T-cell function. The diagnostic value
      of weekly EBV DNA load monitoring was investigated in prospectively collected
      unfractionated whole blood and serum samples of lung transplantation (LTx)
      recipients with and without PTLD. In PTLD patients, 78% of tested whole blood
      samples were above the cut-off value of quantitative competitive polymerase chain
      reaction (Q-PCR) (greater than 2000 EBV DNA copies per mL blood), with the
      majority of patients having high viral loads before and at PTLD diagnosis.
      Especially in a primary EBV-infected patient and in patients with conversion of
      immunosuppressive treatment, rapid increases in peripheral blood EBV DNA load
      diagnosed and predicted PTLD. In non-PTLD transplantation recipients, only 3.4%
      of the whole blood samples was above the cut-off value (P <.0001) despite heavy
      immune suppression and cytomegalovirus (CMV)-related disease. These findings
      illustrate the clinical importance of frequent EBV DNA load monitoring in LTx
      recipients. The increased EBV DNA loads in PTLD patients were restricted to the
      cellular blood compartment, as parallel serum samples were all below cut-off
      value, which indicates absence of lytic viral replication. EBV(+) cells in PTLD
      patients have a very short doubling time, which can be as low as 56 hours,
      thereby creating the need for high screening frequency in high-risk patients.
      Furthermore, it is shown that EBV and CMV can reactivate independently in LTx
      recipients and that EBV DNA load monitoring may be useful in discriminating PTLD
      from rejection.

PMID- 11222358
TI  - Expression of DNA methyltransferases DNMT1, 3A, and 3B in normal hematopoiesis
      and in acute and chronic myelogenous leukemia.
AB  - Aberrant hypermethylation of tumor suppressor genes plays an important role in
      the development of many tumors. Recently identified new DNA methyltransferase
      (DNMT) genes, DNMT3A and DNMT3B, code for de novo methyltransferases. To
      determine the roles of DNMT3A, DNMT3B, as well as DNMT1, in the development of
      leukemia, competitive polymerase chain reaction (PCR) assays were performed and
      the expression levels of DNMTs were measured in normal hematopoiesis, 33 cases of
      acute myelogenous leukemia (AML), and 17 cases of chronic myelogenous leukemia
      (CML). All genes were constitutively expressed, although at different levels, in
      T lymphocytes, monocytes, neutrophils, and normal bone marrow cells.
      Interestingly, DNMT3B was expressed at high levels in CD34(+) bone marrow cells
      but down-regulated in differentiated cells. In AML, 5.3-, 4.4-, and 11.7-fold
      mean increases were seen in the levels of DNMT1, 3A, and 3B, respectively,
      compared with the control bone marrow cells. Although CML cells in the chronic
      phase did not show significant changes, cells in the acute phase showed 3.2-, 4.5
      , and 3.4-fold mean increases in the levels of DNMT1, 3A, and 3B, respectively.
      Using methylation-specific PCR, it was observed that the p15(INAK4B) gene, a cell
      cycle regulator, was methylated in 24 of 33 (72%) cases of AML. Furthermore, AML
      cells with methylated p15(INAK4B) tended to express higher levels of DNMT1 and
      3B. In conclusion, DNMTs were substantially overexpressed in leukemia cells in a
      leukemia type- and stage-specific manner. Up-regulated DNMTs may contribute to
      the pathogenesis of leukemia by inducing aberrant regional hypermethylation.
      (Blood. 2001;97:1172-1179)

PMID- 11222359
TI  - Deleterious clinical effects of transfusion-associated immunomodulation: fact or
      fiction?

PMID- 11222360
TI  - How I treat chronic graft-versus-host disease.
AB  - Allogeneic stem cell transplantation (SCT) is now a commonplace procedure.
      Clinicians who care for patients with hematologic malignancies and aplastic
      anemia are almost certain to follow up patients after SCT. This review is
      intended to help clinicians observe patients for probably the most important late
      complication of SCT, chronic graft-versus-host disease (GVHD). It reviews the
      pathophysiology, risk factors, clinical manifestations, evaluation, treatment,
      and supportive care of chronic GVHD.

PMID- 11222361
TI  - Serum nm23-H1 protein as a prognostic factor in aggressive non-Hodgkin lymphoma.
AB  - Advances in chemotherapy have led to a favorable long-term prognosis in
      approximately 50% of patients with aggressive non-Hodgkin lymphoma (NHL).
      However, the remaining patients do not enjoy such prolonged survival after
      standard treatment. New prognostic factors are needed to define this poor
      prognosis group and to plan an appropriate treatment strategy. It has been
      reported that serum nm23-H1 protein may be a new prognostic factor for aggressive
      NHL. In the present study involving multiple institutions and a large number of
      patients, the level of nm23-H1 protein was compared among different types of
      lymphoma; it was lowest for indolent lymphoma, followed by aggressive lymphoma
      and then highly aggressive lymphoma. In addition, patients with aggressive NHL
      and higher nm23-H1 levels had worse overall and progression-free survival rates
      than those with lower nm23-H1 levels. The nm23-H1 level was also compared between
      patients with diffuse large B-cell lymphoma and patients with peripheral T-cell
      lymphoma. The results suggest that the level of nm23-H1 could serve as a
      prognostic factor in both groups. Moreover, the prognosis of lymphoma patients
      could be ascertained even more precisely by combining soluble interleukin-2
      receptor or soluble CD44 and nm23-H1 levels. A multivariate analysis confirmed
      that the nm23-H1 level is an independent and important prognostic factor in
      aggressive NHL. Therefore, it may provide useful information for clinicians to
      determine the appropriate therapy for each type of lymphoma.

PMID- 11222362
TI  - Improved outcome for children with acute lymphoblastic leukemia: results of Dana
      Farber Consortium Protocol 91-01.
AB  - The Dana-Farber Cancer Institute (DFCI) acute lymphoblastic leukemia (ALL)
      Consortium Protocol 91-01 was designed to improve the outcome of children with
      newly diagnosed ALL while minimizing toxicity. Compared with prior protocols,
      post-remission therapy was intensified by substituting dexamethasone for
      prednisone and prolonging the asparaginase intensification from 20 to 30 weeks.
      Between 1991 and 1995, 377 patients (age, 0-18 years) were enrolled; 137 patients
      were considered standard risk (SR), and 240 patients were high risk (HR).
      Following a 5.0-year median follow-up, the estimated 5-year event-free survival
      (EFS) +/- SE for all patients was 83% +/- 2%, which is superior to prior DFCI ALL
      Consortium protocols conducted between 1981 and 1991 (P =.03). There was no
      significant difference in 5-year EFS based upon risk group (87% +/- 3% for SR and
      81% +/- 3% for HR, P =.24). Age at diagnosis was a statistically significant
      prognostic factor (P =.03), with inferior outcomes observed in infants and
      children 9 years or older. Patients who tolerated 25 or fewer weeks of
      asparaginase had a significantly worse outcome than those who received at least
      26 weeks of asparaginase (P <.01, both univariate and multivariate). Older
      children (at least 9 years of age) were significantly more likely to have
      tolerated 25 or fewer weeks of asparaginase (P <.01). Treatment on Protocol 91-01
      significantly improved the outcome of children with ALL, perhaps due to the
      prolonged asparaginase intensification and/or the use of dexamethasone. The
      inferior outcome of older children may be due, in part, to increased intolerance
      of intensive therapy.

PMID- 11222363
TI  - Development of a prognostic model for grading chronic graft-versus-host disease.
AB  - The disease-specific survival (DSS) of 151 patients with chronic graft-versus
      host disease (cGVHD) was studied in an attempt to stratify patients into risk
      groups and to form a basis for a new grading of cGVHD. The data included the
      outcome and 23 variables at the diagnosis of cGVHD and at the primary treatment
      failure (PTF). Eighty-nine patients (58%) failed primary therapy for cGVHD.
      Nonrelapse mortality was 44% after a median follow-up of 7.8 years. The
      probability of DSS at 10 years after diagnosis of cGVHD (DSS1) and after PTF
      (DSS2) was 51% (95% confidence interval [CI] = 39%, 60%) and 38% (95% CI = 28%,
      49%), respectively. According to multivariate analysis, extensive skin
      involvement (ESI) more than 50% of body surface area; hazard ratio (HR) of 7.0
      (95% CI = 3.6-13.4), thrombocytopenia (TP) (< 100 000/microL; HR, 3.6; 95% CI =
      1.9-6.8), and progressive-type onset (PTO) (HR, 1.7; 95% CI = 0.9-3.0)
      significantly influenced DSS1. These 3 factors and Karnofsky Performance Score of
      less than 50% at PTF were significant predictors for DSS2. The DSS1 at 10 years
      for patients with prognostic factor score (PFS) at diagnosis of 0 (none), 1.9 and
      below [corrected] (ESI only or TP and/or PTO), above 1.9 and not above 3.5
      [corrected] (ESI plus either TP or PTO), and more than 3.5 (all 3 factors) was
      82%, 68%, 34%, and 3% (P =.05, <.001, <.001), respectively. The DSS2 at 5 years
      for patients with PFS at PTF of 0, 2 or less, 2 to 3.5, and more than 3.5 were
      91%, 71%, 22%, and 4% (P =.2,.005, and <.001), respectively. It was concluded
      that these prognostic models might be useful in grouping the patients with
      similar outcome.

PMID- 11222364
TI  - Clinical responses to bone marrow transplantation in children with severe
      osteogenesis imperfecta.
AB  - Preclinical models have shown that transplantation of marrow mesenchymal cells
      has the potential to correct inherited disorders of bone, cartilage, and muscle.
      The report describes clinical responses of the first children to undergo
      allogeneic bone marrow transplantation (BMT) for severe osteogenesis imperfecta
      (OI), a genetic disorder characterized by defective type I collagen, osteopenia,
      bone fragility, severe bony deformities, and growth retardation. Five children
      with severe OI were enrolled in a study of BMT from human leukocyte antigen (HLA)
      compatible sibling donors. Linear growth, bone mineralization, and fracture rate
      were taken as measures of treatment response. The 3 children with documented
      donor osteoblast engraftment had a median 7.5-cm increase in body length (range,
      6.5-8.0 cm) 6 months after transplantation compared with 1.25 cm (range, 1.0-1.5
      cm) for age-matched control patients. These patients gained 21.0 to 65.3 g total
      body bone mineral content by 3 months after treatment or 45% to 77% of their
      baseline values. With extended follow-up, the patients' growth rates either
      slowed or reached a plateau phase. Bone mineral content continued to increase at
      a rate similar to that for weight-matched healthy children, even as growth rates
      declined. These results suggest that BMT from HLA-compatible donors may benefit
      children with severe OI. Further studies are needed to determine the full
      potential of this strategy.

PMID- 11222365
TI  - Direct visualization of cytomegalovirus-specific T-cell reconstitution after
      allogeneic stem cell transplantation.
AB  - Cytomegalovirus (CMV) remains an important cause of morbidity and mortality after
      allogeneic stem cell transplantation (SCT), but cytotoxic T lymphocytes (CTL) may
      play a critical role in controlling CMV reactivation. Fluorescent HLA-peptide
      tetramers containing immunodominant peptides from CMV were used to prospectively
      monitor the recovery of CMV CTL in recipients of allogeneic transplants from
      siblings (n = 13) or unrelated donors (n = 11). In patients given allografts from
      a sibling when both the patient and donor were seropositive for CMV before SCT,
      recovery of CMV-specific CTL was rapid and reached up to 21% of all CD8(+) T
      cells. Early reconstitution of CMV-specific immunity was not observed if either
      the donor or recipient was seronegative for CMV. In recipients of transplants
      from volunteer unrelated donors, recovery of CMV-specific CTL was delayed in
      comparison to that in recipients of transplants from siblings and no CTL were
      observed within the first 100 days after SCT. CTL numbers were increased after
      episodes of CMV reactivation but were suppressed by prednisolone therapy.
      Recovery of CMV-specific CTL to levels greater than 10 x 10(6)/L was associated
      with protection from CMV disease. It was concluded that use of HLA-peptide
      tetramers to quantify CMV CTL is valuable for studying T-cell responses after
      allogeneic SCT. It should allow prediction of CMV reactivation in individual
      patients and assist in the development of adoptive T-cell immunotherapy.

PMID- 11222366
TI  - Differentiation of Langerhans cells in Langerhans cell histiocytosis.
AB  - Langerhans cell histiocytosis (LCH) consists of lesions composed of cells with a
      dendritic Langerhans cell (LC) phenotype. The clinical course of LCH ranges from
      spontaneous resolution to a chronic and sometimes lethal disease. We studied 25
      patients with various clinical forms of the disease. In bone and chronic lesions,
      LCH cells had immature phenotype and function. They coexpressed LC antigens CD1a
      and Langerin together with monocyte antigens CD68 and CD14. Class II antigens
      were intracellular and LCH cells almost never expressed CD83 or CD86 or dendritic
      cell (DC)-Lamp, despite their CD40 expression. Consistently, LCH cells sorted
      from bone lesions (eosinophilic granuloma) poorly stimulated allogeneic T-cell
      proliferation in vitro. Strikingly, however, in vitro treatment with CD40L
      induced the expression of membrane class II and CD86 and strongly increased LCH
      cell allostimulatory activity to a level similar to that of mature DCs. Numerous
      interleukin-10-positive (IL-10(+)), Langerin(-), and CD68(+) macrophages were
      found within bone and lymph node lesions. In patients with self-healing and/or
      isolated cutaneous disease, LCH cells had a more mature phenotype. LCH cells were
      frequently CD14(-) and CD86(+), and macrophages were rare or absent, as were IL
      10-expressing cells. We conclude that LCH cells in the bone and/or chronic forms
      of the disease accumulate within the tissues in an immature state and that most
      probably result from extrinsic signals and may be induced to differentiate toward
      mature DCs after CD40 triggering. Drugs that enhance the in vivo maturation of
      these immature DCs, or that induce their death, may be of therapeutic benefit.

PMID- 11222367
TI  - A Fas-based suicide switch in human T cells for the treatment of graft-versus
      host disease.
AB  - Graft-versus-host disease (GVHD) is a major complication of allogeneic bone
      marrow transplantation. One strategy to treat GVHD is to equip donor T cells with
      a conditional suicide mechanism that can be triggered when GVHD occurs. The
      herpes simplex virus thymidine kinase (HSV-tk)/ganciclovir system used clinically
      has several limitations, including immunogenicity and cell cycle dependence. An
      alternative switch based on chemically inducible apoptosis was designed and
      evaluated. A chimeric human protein was expressed comprising an extracellular
      marker (DeltaLNGFR), the Fas intracellular domain, and 2 copies of an FK506
      binding protein (FKBP). Primary human T lymphocytes retrovirally transduced with
      this construct could be purified to homogeneity using immunomagnetic beads.
      Genetic integrity of the construct was ensured by redesigning repetitive
      sequences. Transduced T cells behaved indistinguishably from untransduced cells,
      retaining the ability to mount a specific antiallogeneic immune response.
      However, they rapidly underwent apoptosis with the addition of subnanomolar
      concentrations of AP1903, a bivalent "dimerizer" drug that binds FKBP and induces
      Fas cross-linking. A single 2-hour treatment eliminated approximately 80% of T
      cells, and multiple exposures induced further apoptosis. T cells were eliminated
      regardless of their proliferation state, suggesting that the AP1903/Fas system,
      which contains only human components, is a promising alternative to HSV-tk for
      treating GVHD.

PMID- 11222368
TI  - Factors influencing in vivo transduction by recombinant adeno-associated viral
      vectors expressing the human factor IX cDNA.
AB  - Long-term expression of coagulation factor IX (FIX) has been observed in murine
      and canine models following administration of recombinant adeno-associated viral
      (rAAV) vectors into either the portal vein or muscle. These studies were designed
      to evaluate factors that influence rAAV-mediated FIX expression. Stable and
      persistent human FIX (hFIX) expression (> 22 weeks) was observed from 4 vectors
      after injection into the portal circulation of immunodeficient mice. The level of
      expression was dependent on promoter with the highest expression, 10% of
      physiologic levels, observed with a vector containing the cytomegalovirus (CMV)
      enhancer/beta-actin promoter complex (CAGG). The kinetics of expression after
      injection of vector particles into muscle, tail vein, or portal vein were similar
      with hFIX detectable at 2 weeks and reaching a plateau by 8 weeks. For a given
      dose, intraportal administration of rAAV CAGG-FIX resulted in a 1.5-fold or 4
      fold higher level of hFIX compared to tail vein or intramuscular injections,
      respectively. Polymerase chain reaction analysis demonstrated predominant
      localization of the rAAV FIX genome in liver and spleen after tail vein injection
      with a higher proportion in liver after portal vein injection. Therapeutic levels
      of hFIX were detected in the majority of immunocompetent mice (21 of 22)
      following intravenous administration of rAAV vector without the development of
      anti-hFIX antibodies, but hFIX was not detected in 14 immunocompetent mice
      following intramuscular administration, irrespective of strain. Instead,
      neutralizing anti-hFIX antibodies were detected in all the mice. These
      observations may have important implications for hemophilia B gene therapy with
      rAAV vectors.

PMID- 11222369
TI  - Initiation of polyoma virus origin-dependent DNA replication through STAT5
      activation by human granulocyte-macrophage colony-stimulating factor.
AB  - Several lines of evidence indicate that transcriptional activation is coupled
      with DNA replication initiation, but the nature of initiation of DNA replication
      in mammalian cells is unclear. Polyoma virus replicon is an excellent system to
      analyze the initiation of DNA replication in murine cells because its replication
      requires an enhancer, and all components of replication machinery, except for DNA
      helicase large T antigen, are supplied by host cells. This system was used to
      examine the role of signal transducer and activator of transcription (STAT5) in
      replication initiation of polyoma replicon in the mouse lymphoid cell line BA/F3.
      The plasmid with tandem repeats of consensus STAT5 binding sites followed by
      polyoma replication origin was replicated by stimulation with human granulocyte
      macrophage colony-stimulating factor (hGM-CSF) in the presence of polyoma large T
      antigen in BA/F3 cells. Mutation analysis of the hGM-CSF receptor beta subunit
      revealed that only the box1 region is essential, and the C-terminal tyrosine
      residues are dispensable for the activity. Addition of the tyrosine kinase
      inhibitor genistein suppressed this replication without affecting transcriptional
      activation of STAT5. Because deletion analysis of STAT5 indicates the importance
      of the C-terminal transcriptional activation domain of STAT5 for the initiation
      of replication, the role of this region in the activation of replication was
      examined with a GAL4-STAT5 fusion protein. GAL4-STAT5 activated replication of
      the plasmid containing tandem repeats of GAL4 binding sites and polyoma
      replication origin in BA/F3 cells. Mutation analysis of GAL4-STAT5 indicated that
      multiple serine residues coordinately have a role in activating replication. This
      is the first direct evidence indicating the potential involvement of STAT5 in
      replication.

PMID- 11222370
TI  - Assessment of mechanism of acquired skewed X inactivation by analysis of twins.
AB  - Skewed X-chromosome inactivation in peripheral blood granulocytes becomes more
      frequent with increasing age, affecting up to half of those over 75 years old. To
      investigate the mechanisms underlying this phenomenon, X-inactivation profiles in
      33 monozygotic and 22 dizygotic elderly twin pairs were studied. Differential
      methylation-sensitive restriction enzyme cutting at a hypervariable locus in the
      human androgen receptor gene (HUMARA) was studied on purified granulocytes using
      T cells as controls. A large genetic effect on skewed granulocytic X inactivation
      was shown (P <.05); heritability was estimated to be 0.68. A minor part (SD.0151
      relative allele frequency [ie, larger/smaller] units) of the observed variance is
      due to experimental error. A further contributor to acquired skewing is
      stochastic asymmetric stem cell division, which was modeled and shown as unlikely
      to account for a substantial part of variance. Two monozygotic twin pairs had X
      inactivation ratios skewed markedly in opposite directions, evidence for a
      further stochastic mechanism, suggestive of a single overrepresented clone. In
      conclusion, all 3 suggested mechanisms contribute to acquired X inactivation but
      the dominant mechanism is genetic selection. The observed proportion of
      putatively clonal hematopoiesis is similar to the lifetime incidence of
      hematopoietic stem cell malignancy consistent with the concept that clonal
      hematopoiesis precedes stem cell malignancy.

PMID- 11222371
TI  - Synergistic mobilization of hemopoietic progenitor cells using concurrent beta1
      and beta2 integrin blockade or beta2-deficient mice.
AB  - The hierarchy of cytoadhesion molecules involved in hematopoietic/stem progenitor
      cell mobilization has not yet been delineated. Previous studies have suggested an
      important role for alpha4beta1 integrin in this process. To test whether
      mobilization involves dynamic interactions of alpha4beta1 with other integrins on
      hematopoietic cells, especially the beta2 integrins, mice and primates were
      treated with anti-beta1 or anti-beta2 antibodies alone or in combination. A
      single injection of anti-alpha4beta1 antibody elicited reproducible mobilization
      in contrast to other antibodies, and 3 injections yielded higher mobilization
      efficiency than each of the other antibodies. When the anti-beta2 (anti-CD11a or
      anti-CD18) or anti-alpha5/beta1 integrin antibody was combined with anti-alpha4,
      an augmentation in mobilization was seen that was either additive or synergistic,
      depending on the potency of the antibody used. Synergy between anti-alpha4 and
      anti-CD18 (beta(2)) antibody blockade was seen in primates and confirmed in anti
      alpha4-treated CD18-deficient mice. In the latter, there was a 49-fold increase
      in mobilization with anti-alpha4, much higher than in littermate control animals,
      in CD18 hypomorphic mice, or in other strains of mice tested. Data from both the
      antibody blockade and gene-targeted mice suggest that the cooperativity of
      alpha4beta1 with beta2 integrins becomes evident when they are concurrently
      inhibited. It is unclear whether this cooperativity is exerted at the stage of
      reversible adhesion versus migration, and enhancement of and whether the 2
      integrins work in a sequential or parallel manner. Whatever the mechanism, the
      data provide a novel example of beta1 and beta2 integrin crosstalk in
      stem/progenitor cell mobilization.

PMID- 11222372
TI  - Protein phosphatase 2A activates the proapoptotic function of BAD in interleukin-
      3-dependent lymphoid cells by a mechanism requiring 14-3-3 dissociation.
AB  - BAD is a proapoptotic member of the BCL-2 family of proteins, which play a major
      role in regulating apoptosis in cytokine-dependent hematopoietic cells. The
      function of BAD is regulated by reversible phosphorylation. Deprivation of
      survival factors induces BAD dephosphorylation, resulting in apoptosis. Serine
      threonine phosphatase activity dephosphorylated BAD in interleukin-3-dependent
      FL5.12 lymphoid cells. Inhibition of PP2A activity by treatment of cells with
      PP2A-selective inhibitors, okadaic acid and fostriecin, prevented BAD
      dephosphorylation in these cells. Conversely, BAD dephosphorylation was not
      inhibited by the PP1-selective inhibitor tautomycin. In cell-free extracts, BAD
      phosphatase activity was also inhibited by the PP2A-selective inhibitors okadaic
      acid and fostriecin, but not by the PP1-specific protein inhibitor I-2.
      Dissociation of 14-3-3 from BAD was a prerequisite for BAD dephosphorylation in
      vitro, suggesting a mechanism by which 14-3-3 can regulate the activation of the
      proapoptotic function of BAD in vivo. Significantly, the inhibition of BAD
      phosphatase activity rescued cell death induced by survival factor withdrawal in
      FL5.12 cells expressing wild-type BAD but not phosphorylation-defective mutant
      BAD. These data indicate that PP2A, or a PP2A-like enzyme, dephosphorylates BAD
      and, in conjunction with 14-3-3, modulates cytokine-mediated survival.

PMID- 11222373
TI  - Early growth response gene 1 stimulates development of hematopoietic progenitor
      cells along the macrophage lineage at the expense of the granulocyte and
      erythroid lineages.
AB  - Using a variety of differentiation-inducible myeloid cell lines, we previously
      showed that the zinc-finger transcription factor early growth response gene 1
      (Egr-1) is a positive modulator of macrophage differentiation and negatively
      regulates granulocytic differentiation. In this study, high-efficiency retroviral
      transduction was used to ectopically express Egr-1 in myeloid-enriched or stem
      cell-enriched bone marrow cultures to explore its effect on the development of
      hematopoietic progenitors in vitro and in lethally irradiated mice. It was found
      that ectopic Egr-1 expression in normal hematopoietic progenitors stimulates
      development along the macrophage lineage at the expense of development along the
      granulocyte or erythroid lineages, regardless of the cytokine used. Moreover, Egr
      1 accelerated macrophage development by suppressing the proliferative phase of
      the growth-to-macrophage developmental program. The remarkable ability of Egr-1
      to dictate macrophage development at the expense of development along other
      lineages resulted in failure of Egr-1-infected hematopoietic progenitors to
      repopulate the bone marrow and spleen, and thereby prevent death, in lethally
      irradiated mice. These observations further highlight the role Egr-1 plays in
      monocytic differentiation and growth suppression.

PMID- 11222374
TI  - Unique effects of zinc protoporphyrin on HO-1 induction and apoptosis.
AB  - Zinc protoporphyrin (ZnPP), a naturally occurring molecule, is increased in iron
      deficiency and lead intoxication. ZnPP can also induce heme oxygenase (HO-1), the
      enzyme it competitively inhibits. In cultured cells (HA-1), ZnPP was the
      strongest HO-1 inducer of any metalloporphyrin (MP) tested. This was not due to
      increased oxidative stress, enhanced binding at metal response element, nor
      increased binding at activator protein-1 (AP-1) or SP-1 sites on HO-1. Only ZnPP,
      however, increased binding of nuclear proteins to early growth response-1 (Egr-1)
      protein consensus sequence. Pretreatment of HA-1 with cycloheximide inhibited
      ZnPP-induced HO-1 messenger RNA (mRNA) by 55%. Incubation with antisense Egr-1
      oligomers decreased ZnPP-induced HO-1 expression by 47%. Furthermore, the level
      of HO-1 mRNA induction by ZnPP was 2-fold less in Egr-1-deficient fibroblasts
      than in wild-type cells. Because no Egr-1 binding site was previously identified
      on the HO-1 promoter, HA-1 cells were transfected with HO-1 CAT constructs
      containing segments of a 12.5-kb enhancer region of HO-1. A 196-bp fragment (RH)
      located approximately 9.5 kb upstream of the transcription start site mediated HO
      1 induction by ZnPP alone. DNase I footprinting analysis further revealed that
      nuclear proteins bound to a 50-bp sequence in the RH. Within this sequence, a
      novel 9-bp region with 78% homology to the Egr-1 consensus sequence was
      identified further suggesting that Egr-1 partially mediates HO-1 induction by
      ZnPP. Lastly, increased apoptosis and nuclear localization were only seen with
      ZnPP, suggesting that increased ZnPP in disease states may serve as a cellular
      signaling mechanism.

PMID- 11222375
TI  - Positive and negative regulation of granulopoiesis by endogenous RARalpha.
AB  - Acute promyelocytic leukemia (APL) is always associated with chromosomal
      translocations that disrupt the retinoic acid receptor alpha (RARalpha) gene.
      Whether these translocations relate to a role for endogenous RARalpha in normal
      granulopoiesis remains uncertain because most studies addressing this question
      have used non-physiological overexpression systems. Granulocyte differentiation
      in cells derived from RARalpha-deficient (RARalpha(-/-)) mice was studied and
      evaluated in the context of agonist-bound and ligand-free RARalpha. Our results
      demonstrate that RARalpha is dispensable for granulopoiesis, as RARalpha(-/-)
      mice have a normal granulocyte population despite an impaired ability to respond
      to retinoids. However, although it is not absolutely required, RARalpha can
      bidirectionally modulate granulopoiesis. RARalpha stimulates differentiation in
      response to exogenous retinoic acid. Furthermore, endogenous retinoids control
      granulopoiesis in vivo, as either vitamin A-deficient mice or animals treated
      with an RAR antagonist accumulate more immature granulocytes in their bone
      marrow. Conversely, RARalpha acts to limit differentiation in the absence of
      ligand because granulocyte precursors from RARalpha(-/-) mice differentiate
      earlier in culture. Thus, the block in granulopoiesis exerted by RARalpha fusion
      proteins expressed in APL cells may correspond to an amplification of a normal
      function of unliganded RARalpha.

PMID- 11222377
TI  - Autosomal dominant macrothrombocytopenia in Italy is most frequently a type of
      heterozygous Bernard-Soulier syndrome.
AB  - A form of autosomal dominant macrothrombocytopenia is characterized by mild or no
      clinical symptoms, normal platelet function, and normal megakaryocyte count.
      Because this condition has so far received little attention, patients are subject
      to misdiagnosis and inappropriate therapy. To identify the molecular basis of
      this disease, 12 Italian families were studied by linkage analysis and mutation
      screening. Flow cytometry evaluations of platelet membrane glycoproteins (GPs)
      were also performed. Linkage analysis in 2 large families localized the gene to
      chromosome 17p, in an interval containing an excellent candidate, the GPIbalpha
      gene. GPIbalpha, together with other proteins, constitutes the plasma von
      Willebrand factor (vWF) receptor, which is altered in Bernard-Soulier syndrome
      (BSS). In 6 of 12 families, a heterozygous Ala156Val missense substitution was
      identified. Platelet membrane GP studies were performed in 10 patients. Eight
      were distinguished by a reduction of GPs comparable to that found in a BSS
      heterozygous condition, whereas the other 2, without the Ala156Val mutation, had
      a normal content of platelet GPs. In conclusion, the current study provides
      evidence that most (10 of 12) patients with an original diagnosis of autosomal
      dominant macrothrombocytopenia shared clinical and molecular features with the
      heterozygous BSS phenotype. The remaining 2 affected subjects represented
      patients with "true" autosomal dominant macrothrombocytopenia; the GPIb/IX/V
      complex was normally distributed on the surface of their platelets. Thus, the
      diagnosis of heterozygous BSS must always be suspected in patients with inherited
      thrombocytopenia and platelet macrocytosis.

PMID- 11222376
TI  - A permissive role for tumor necrosis factor in vascular endothelial growth factor
      induced vascular permeability.
AB  - Vascular endothelial growth factor (VEGF) induces both angiogenesis and an
      increase in vascular permeability, 2 processes that are considered to be
      important for both tumor growth and the delivery of drugs to the site of tumors.
      This study demonstrates that transmembrane expression of tumor necrosis factor
      (tmTNF) is up-regulated in the endothelium of a murine methylcholanthrene (meth
      A)-induced sarcoma in comparison to the adjacent normal dermal vasculature and is
      also present on cultivated human endothelial cells. It is further shown that
      tmTNF is required for VEGF-mediated endothelial hyperpermeability in vitro and in
      vivo. This permissive activity of TNF appears to be selective, because anti-TNF
      antibodies ablated the VEGF-induced permeability but not proliferation of
      cultivated human endothelial cells. Furthermore, tnf gene-deficient mice show no
      obvious defects in vascularization and develop normally but failed to respond to
      administration of VEGF with an increase in vascular permeability. Subsequent
      studies indicated that the tmTNF and VEGF signaling pathways converge at the
      level of a secondary messenger, the "stress-activated protein kinase-2" (SAPK
      2)/p38: (1) up-regulated endothelial expression of tmTNF resulted in the
      continuous activation of SAPK-2/p38 in vitro, and (2) an inhibitor of SAPK-2/p38
      activation abolished the vascular permeability activity of VEGF in vivo. In
      conclusion, the study's finding that continuous autocrine signaling by tmTNF
      sensitizes endothelial cells to respond to VEGF by increasing their vascular
      permeability provides new therapeutic concepts for manipulating vascular
      hyperpermeability.

PMID- 11222378
TI  - Dissociation of thymic positive and negative selection in transgenic mice
      expressing major histocompatibility complex class I molecules exclusively on
      thymic cortical epithelial cells.
AB  - Thymic positive and negative selection of developing T lymphocytes confronts us
      with a paradox: How can a T-cell antigen receptor (TCR)-major histocompatibility
      complex (MHC)/peptide interaction in the former process lead to transduction of
      signals allowing for cell survival and in the latter induce programmed cell death
      or a hyporesponsive state known as anergy? One of the hypotheses put forward
      states that the outcome of a TCR-MHC/peptide interaction depends on the cell type
      presenting the selecting ligand to the developing thymocyte. Here we describe the
      development and lack of self-tolerance of CD8(+) T lymphocytes in transgenic mice
      expressing MHC class I molecules in the thymus exclusively on cortical epithelial
      cells. Despite the absence of MHC class I expression on professional antigen
      presenting cells, normal numbers of CD8(+) cells were observed in the periphery.
      Upon specific activation, transgenic CD8(+) T cells efficiently lysed syngeneic
      MHC class I(+) targets in vitro and in vivo, indicating that thymic cortical
      epithelium (in contrast to medullary epithelium and antigen-presenting cells of
      hematopoietic origin) is incapable of tolerance induction. Thus,
      compartmentalization of the antigen-presenting cells involved in thymic positive
      selection and tolerance induction can (at least in part) explain the
      positive/negative selection paradox.

PMID- 11222379
TI  - SHIP's C-terminus is essential for its hydrolysis of PIP3 and inhibition of mast
      cell degranulation.
AB  - The SH2-containing inositol-5'-phosphatase, SHIP, restrains bone marrow-derived
      mast cell (BMMC) degranulation, at least in part, by hydrolyzing
      phosphatidylinositol (PI)-3-kinase generated PI-3,4,5-P(3) (PIP3) to PI-3,4-P(2).
      To determine which domains within SHIP influence its ability to hydrolyze PIP3,
      bone marrow from SHIP(-/-) mice was retrovirally infected with various SHIP
      constructs. Introduction of wild-type SHIP into SHIP(-/-) BMMCs reverted the
      Steel factor (SF)-induced increases in PIP3, calcium entry, and degranulation to
      those observed in SHIP(+/+) BMMCs. A 5'-phosphatase dead SHIP, however, could not
      revert the SHIP(-/-) response, whereas a SHIP mutant in which the 2 NPXY motifs
      were converted to NPXFs (2NPXF) could partially revert the SHIP(-/-) response. SF
      stimulation of BMMCs expressing the 2NPXF, which could not bind Shc, led to the
      same level of mitogen-activated protein kinase (MAPK) phosphorylation as that
      seen in BMMCs expressing the other constructs. Surprisingly, C-terminally
      truncated forms of SHIP, lacking different amounts of the proline rich C
      terminus, could not revert the SHIP(-/-) response at all. These results suggest
      that the C-terminus plays a critical role in enabling SHIP to hydrolyze PIP(3)
      and inhibit BMMC degranulation.

PMID- 11222380
TI  - SH2 domain-mediated targeting, but not localization, of Syk in the plasma
      membrane is critical for FcepsilonRI signaling.
AB  - Aggregation of the high-affinity IgE receptor induces the tyrosine
      phosphorylation of subunits of the receptor and the subsequent association with
      the receptor of the cytosolic protein tyrosine kinase Syk. The current
      experiments examined the functional importance of membrane association of Syk and
      the role of the SH2 domain in receptor-mediated signal transduction. Wild-type
      Syk and chimeric Syk molecules with the c-Src myristylation sequence at the amino
      terminus were expressed in a Syk-negative mast cell line. Chimeric Syk with the
      myristylation sequence was membrane associated, and a small fraction was
      constitutively colocalized with FcepsilonRI, Lyn, and LAT (linker for T-cell
      activation) in the glycolipid-enriched microdomains or rafts. However, even under
      these conditions, the tyrosine phosphorylation of Syk and the downstream
      propagation of signals required FcepsilonRI aggregation. This chimeric Syk was
      less active than wild-type Syk in FcepsilonRI-mediated signal transduction. In
      contrast, a truncated membrane-associated form of Syk that lacked the SH2 domains
      was not tyrosine phosphorylated by receptor aggregation and failed to transduce
      intracellular signals. These findings suggest that SH2 domain-mediated membrane
      translocation of Syk is essential for the FcepsilonRI-mediated activation of Syk
      for downstream signaling events leading to histamine release. Furthermore, the
      localization of Syk in glycolipid-enriched microdomains by itself is not enough
      to generate or enhance signaling events.

PMID- 11222381
TI  - Thymic emigrants isolated by a new method possess unique phenotypic and
      functional properties.
AB  - T cells that emigrate from the thymus have primarily been studied in vivo using
      fluorescent dye injection of the thymus. This study examined the properties of
      thymocytes that emigrate from cultured thymic lobes in organ culture. Under these
      conditions, thymic emigrants displayed the expected phenotype, that of mature
      thymocytes expressing high levels of T-cell receptor (TCR-alphabeta) and either
      CD4 or CD8, and were observed to emigrate within 24 hours of positive selection.
      Emigration was inhibited by cytochalasin D, pertussis toxin, or Clostridium
      difficile toxin B, implicating an active motility process. Most of the surface
      markers on alphabeta-thymic emigrants (Thy1, CD44, CD69, CD25, leukocyte
      functional antigen-1, intercellular adhesion molecule-1, alpha(4)-integrin,
      alpha(5)-integrin, CD45, and CD28) were expressed at a surface density similar to
      that on mature intrathymic cells and peripheral splenic T cells. Heterogeneous
      expression of L-selectin and heat-stable antigen (HSA) suggested that subsets
      emerge from the thymus with a commitment to different migration patterns. The
      only marker on emigrants not found on either intrathymic cells or mature spleen T
      cells was CTLA-4, which could dampen the response of emigrants to peripheral
      antigens. Antigen responsivenes measured in vitro against allogeneic dendritic
      cells showed a proliferative response comparable to that of splenic T cells. In
      vivo, however, thymic emigrants failed to induce an acute graft-versus-host
      reaction in allogeneic severe combined immunodeficiency recipients. This suggests
      that a mechanism operating in vivo, perhaps tolerance or migration pattern,
      attenuates the response of emigrants against antigens that did not induce their
      deletion in the thymus.

PMID- 11222382
TI  - Idiotype-encoding recombinant adenoviruses provide protective immunity against
      murine B-cell lymphomas.
AB  - Vaccination with tumor-specific immunoglobulin or idiotype (Id) is a promising
      new form of immunotherapy for B-cell malignancies. Id protein vaccination has
      demonstrated clinical activity in B-cell lymphomas, yet it requires the laborious
      and time-consuming procedures of tumor-myeloma cell hybridization, large-scale in
      vitro culture, and protein purification. Recombinant adenoviruses are highly
      efficient and immunogenic gene transfer vehicles from which individualized
      vaccines can be rapidly assembled using polymerase chain reaction-amplified tumor
      Id genes. Id-encoding adenoviruses were evaluated as vaccines in 2 murine B-cell
      lymphoma models. A single injection of recombinant Id adenovirus provided
      protection from subsequent tumor challenge that was equivalent or superior to
      that afforded by Id protein vaccination. Protected mice had substantial serum
      titers of Id-specific antibodies. When used in conjunction with chemotherapy,
      vaccination also prolonged the survival of mice bearing pre-existing tumor.
      Mechanistic studies demonstrated that tumor protection was not dependent upon T
      cells. Importantly, in mice prevaccinated with an irrelevant adenovirus, tumor
      protection following vaccination with Id adenovirus was not significantly
      impaired. These findings have implications for the design of future lymphoma
      immunotherapy trials.

PMID- 11222383
TI  - Activation of caspase-8 in drug-induced apoptosis of B-lymphoid cells is
      independent of CD95/Fas receptor-ligand interaction and occurs downstream of
      caspase-3.
AB  - The activation of caspase-8, a crucial upstream mediator of death receptor
      signaling, was investigated in epirubicin- and Taxol-induced apoptosis of B
      lymphoma cells. This study was performed because the CD95/Fas receptor-ligand
      interaction, recruitment of the Fas-associated death domain (FADD) adaptor
      protein, and subsequent activation of procaspase-8 have been implicated in the
      execution of drug-induced apoptosis in other cell types. Indeed, active caspase-8
      was readily detected after treatment of mature and immature B-lymphoid cells with
      epirubicin or Taxol. However, neither constitutive nor drug-induced expression of
      the CD95/Fas ligand was detectable in B-lymphoma cells. Furthermore,
      overexpression of a dominant-negative FADD mutant (FADDdn) did not block caspase
      8 processing and subsequent DNA fragmentation, indicating that drug-induced
      caspase-8 activation was mediated by a CD95/Fas-independent mechanism. Instead,
      caspase-8 cleavage was slightly preceded by activation of caspase-3, suggesting
      that drug-induced caspase-8 activation in B-lymphoma cells is a downstream event
      mediated by other caspases. This assumption was confirmed in 2 experimental
      systems-zDEVD-fmk, a cell-permeable inhibitor of caspase-3-like activity, blocked
      drug-induced caspase-8 cleavage, and depletion of caspase-3 from cell extracts
      impaired caspase-8 cleavage after in vitro activation with dATP and cytochrome c.
      Thus, these data indicate that drug-induced caspase-8 activation in B-lymphoma
      cells is independent of death receptor signaling and is mediated by
      postmitochondrial caspase-3 activation.

PMID- 11222384
TI  - CD4(+) cutaneous T-cell lymphoma cells express the p140-killer cell
      immunoglobulin-like receptor.
AB  - Tumor cells of patients with cutaneous T-cell lymphoma (CTCL) have the cell
      surface phenotype of mature T-helper lymphocytes, and it may be impossible to
      differentiate them from nonmalignant lymphocytes in skin and blood. Until now, no
      specific cell membrane marker of CTCL has been reported. In the current study, it
      is reported for the first time that CTCL cells express the major
      histocompatibility complex class I binding p140-killer cell immunoglobulin-like
      receptor, which has been described on a minor subset of natural killer
      lymphocytes and on a marginal circulating CD8(+) T lymphocyte subset.
      Interestingly, the molecular characterization of this KIR expressed by CTCL
      allowed us to isolate a novel allelic form of p140-KIR3DL, resulting in 4 amino
      acid substitutions, 3 in the extracellular immunoglobulin-like domain of the
      protein and one in the cytoplasmic region. This finding is likely to be important
      both for the pathophysiology and for the clinical treatment of patients with
      CTCL.

PMID- 11222385
TI  - Homodimers but not monomers of Rituxan (chimeric anti-CD20) induce apoptosis in
      human B-lymphoma cells and synergize with a chemotherapeutic agent and an
      immunotoxin.
AB  - In 1997, a chimeric anti-CD20 monoclonal antibody (mAb) (Rituxan) was approved
      for the treatment of low-grade/follicular B-cell lymphoma. Rituxan has a long
      half-life and low immunogenicity, and it mediates effector function. Rituxan
      induces apoptosis in some tumor cell lines in vitro. Previous studies with mAbs
      that react with neoplastic B cells have demonstrated that homodimers of
      immunoglobulin G ([IgG](2)) often inhibit cell growth more effectively than their
      monomeric (IgG)(1) counterparts. In this study, the ability of IgG or F(ab')(2)
      homodimers vs monomers of Rituxan were compared for their ability to inhibit the
      growth of several different B-lymphoma cell lines in vitro. It was found that
      homodimers of Rituxan had superior antigrowth activity in vitro and that
      F(ab')(2) homodimers were the most active. Homodimers, but not monomers, of
      Rituxan induced both apoptosis and necrosis of several B-cell lymphoma lines in
      vitro; the inhibition of cell growth was not dependent upon the presence of Fc
      receptors or upon 10-fold or greater differences in the density of CD20 on the
      target cells. Rituxan homodimers, compared with monomers, also rendered drug
      resistant CD20(+) B-lymphoma cells more sensitive to chemotherapeutic agents and
      synergized with an anti-CD22 immunotoxin in vitro.

PMID- 11222386
TI  - Treatment of Bcr/Abl-positive acute lymphoblastic leukemia in P190 transgenic
      mice with the farnesyl transferase inhibitor SCH66336.
AB  - The Philadelphia (Ph) chromosome is found in approximately 3% of pediatric
      patients with acute lymphoblastic leukemia (ALL) and the percentage markedly
      increases in adult patients. The prognosis for this class of patients is poor,
      and no standard chemotherapy combination so far has demonstrated long-term
      efficacy. The Ph-translocation joins the BCR and ABL genes and leads to
      expression of a chimeric Bcr/Abl protein with enhanced tyrosine kinase activity.
      This increase in activity leads to malignant transformation by interference with
      basic cellular functions such as the control of proliferation, adherence to
      stroma and extracellular matrix, and apoptosis. One important pathway activated
      by Bcr/Abl is the Ras pathway. Ras proteins have to undergo a series of
      posttranslational modifications to become biologically active. The first
      modification is the farnesylation of the C-terminus catalyzed by farnesyl
      transferase. We studied the effect of the farnesyl transferase inhibitor SCH66336
      in an in vivo murine model of Bcr/Abl-positive acute lymphoblastic leukemia. In
      the early leukemic phase, mice were randomly assigned to a treatment, a vehicle,
      and a nontreatment group. The treatment was well tolerated without any detectable
      side effects. All animals of the control groups died of leukemia/lymphoma within
      103 days (range, 18-103 days). In contrast, 80% of the drug-receiving group
      survived without any signs of leukemia or lymphoma until termination of
      treatment, after a median treatment period of 200 days (range, 179-232 days). We
      conclude that farnesyl transferase inhibitor SCH66336 is able to revert early
      signs of leukemia and significantly prolongs survival in a murine ALL model.

PMID- 11222387
TI  - Activity of the farnesyl protein transferase inhibitor SCH66336 against BCR/ABL
      induced murine leukemia and primary cells from patients with chronic myeloid
      leukemia.
AB  - BCR/ABL, the oncoprotein responsible for chronic myeloid leukemia (CML),
      transforms hematopoietic cells through both Ras-dependent and -independent
      mechanisms. Farnesyl protein transferase inhibitors (FTIs) were designed to block
      mutant Ras signaling, but they also inhibit the growth of transformed cells with
      wild-type Ras, implying that other farnesylated targets contribute to FTI action.
      In the current study, the clinical candidate FTI SCH66336 was characterized for
      its ability to inhibit BCR/ABL transformation. When tested against BCR/ABL-BaF3
      cells, a murine cell line that is leukemogenic in mice, SCH66336 potently
      inhibited soft agar colony formation, slowed proliferation, and sensitized cells
      to apoptotic stimuli. Quantification of activated guanosine triphosphate (GTP)
      bound Ras protein and electrophoretic mobility shift assays for AP-1 DNA binding
      showed that Ras effector pathways are inhibited by SCH66336. However, SCH66336
      was more inhibitory than dominant-negative Ras in assays of soft agar colony
      formation and cell proliferation, suggesting activity against targets other than
      Ras. Cell cycle analysis of BCR/ABL-BaF3 cells treated with SCH66336 revealed
      G2/M blockade, consistent with recent reports that centromeric proteins that
      regulate the G2/M checkpoint are critical farnesylated targets of FTI action.
      Mice injected intravenously with BCR/ABL-BaF3 cells developed acute leukemia and
      died within 4 weeks with massive splenomegaly, elevated white blood cell counts,
      and anemia. In contrast, nearly all mice treated with SCH66336 survived and have
      remained disease-free for more than a year. Furthermore, SCH66336 selectively
      inhibited the hematopoietic colony formation of primary human CML cells. As an
      oral, nontoxic compound with a mechanism of action distinct from that of ABL
      tyrosine kinase inhibition, FTI SCH66336 shows promise for the treatment of
      BCR/ABL-induced leukemia.

PMID- 11222388
TI  - The antiangiogenic protein kinase inhibitors SU5416 and SU6668 inhibit the SCF
      receptor (c-kit) in a human myeloid leukemia cell line and in acute myeloid
      leukemia blasts.
AB  - SU5416 and SU6668 are potent antiangiogenic small-molecule inhibitors of receptor
      tyrosine kinases, including those of the vascular endothelial growth factor and
      platelet-derived growth factor receptor families. The stem cell factor (SCF)
      receptor, c-kit, is structurally related to these receptors and, although not
      expressed on mature peripheral blood cells, is expressed in leukemic blasts
      derived from 60% to 80% of acute myeloid leukemia (AML) patients. The c-kit
      kinase inhibitory activity of SU5416 and SU6668 was evaluated in MO7E cells, a
      human myeloid leukemia cell line. Tyrosine autophosphorylation of the receptor,
      induced by SCF, was inhibited in these cells by SU5416 and SU6668 in a dose
      dependent manner (inhibitory concentration of 50% [IC(50)] 0.1-1 microM).
      Inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation,
      a signaling event downstream of c-kit activation, was also inhibited in a dose
      dependent manner. Both compounds also inhibited SCF-induced proliferation of MO7E
      cells (IC(50) 0.1 microM for SU5416; 0.29 microM for SU6668). Furthermore, both
      SU5416 and SU6668 induced apoptosis in a dose- and time-dependent manner as
      measured by the increase in activated caspase-3 and the enhanced cleavage of its
      substrate poly(ADP-ribose) polymerase. These findings with MO7E cells were
      extended to leukemic blasts from c-kit(+) patients. In patient blasts, both
      SU5416 and SU6668 inhibited SCF-induced phosphorylation of c-kit and ERK1/2 and
      induced apoptosis. These studies indicate that SU5416 and SU6668 inhibit biologic
      functions of c-kit in addition to exhibiting antiangiogenic properties and
      suggest that the combination of these activities may provide a novel therapeutic
      approach for the treatment of AML.

PMID- 11222389
TI  - Low NAD(P)H:quinone oxidoreductase 1 activity is associated with increased risk
      of acute leukemia in adults.
AB  - NAD(P)H:quinone oxidoreductase 1 (NQO1) is an enzyme that detoxifies quinones and
      reduces oxidative stress. A cysteine-to-threonine (C --> T) substitution
      polymorphism at nucleotide 609 of the NQO1 complementary DNA (NQO1 C609T) results
      in a lowering of NQO1 activity. Individuals homozygous for this mutation have no
      NQO1 activity, and heterozygotes have low to intermediate activity compared with
      people with wild type. DNA samples from 493 adult de novo acute leukemia patients
      and 838 matched controls were genotyped for NQO1 C609T. The majority of cases
      were diagnosed as acute myeloid leukemia (AML) (n = 420); 67 as acute
      lymphoblastic leukemia (ALL); and 6 as other forms of acute leukemia. The
      frequency of cases with low or null NQO1 activity (heterozygote + homozygous
      mutant) was significantly higher among total acute leukemia case subjects
      compared with their matched controls (odds ratio [OR] = 1.49; 95% confidence
      interval [CI], 1.17-1.89). Both ALL (OR = 1.93; 95% CI, 0.96-3.87) and AML case
      subjects (OR = 1.47; 95% CI, 1.13-1.90) exhibited a higher frequency of low or
      null NQO1 genotypes than controls. For de novo AML, the most significant effect
      of low or null NQO1 activity was observed among the 88 cases harboring
      translocations and inversions (OR = 2.39; 95% CI, 1.34-4.27) and was especially
      high for those harboring inv(16) (OR = 8.13; 95% CI, 1.43-46.42). These findings
      were confirmed in a second group of 217 de novo AML cases with known
      cytogenetics. Thus, inheritance of NQO1 C609T confers an increased risk of de
      novo acute leukemia in adults, implicating quinones and related compounds that
      generate oxidative stress in producing acute leukemia.

PMID- 11222390
TI  - Vascular endothelial cell growth factor is an autocrine promoter of abnormal
      localized immature myeloid precursors and leukemia progenitor formation in
      myelodysplastic syndromes.
AB  - Vascular endothelial growth factor (VEGF) is a potent angiogenic peptide with
      biologic effects that include regulation of hematopoietic stem cell development,
      extracellular matrix remodeling, and inflammatory cytokine generation. To
      delineate the potential role of VEGF in patients with myelodysplastic syndrome
      (MDS), VEGF protein and receptor expression and its functional significance in
      MDS bone marrow (BM) were evaluated. In BM clot sections from normal donors, low
      intensity cytoplasmic VEGF expression was detected infrequently in isolated
      myeloid elements. However, monocytoid precursors in chronic myelomonocytic
      leukemia (CMML) expressed VEGF in an intense cytoplasmic pattern with membranous
      co-expression of the Flt-1 or KDR receptors, or both. In situ hybridization
      confirmed the presence of VEGF mRNA in the neoplastic monocytes. In acute
      myelogenous leukemia (AML) and other MDS subtypes, intense co-expression of VEGF
      and one or both receptors was detected in myeloblasts and immature myeloid
      elements, whereas erythroid precursors and lymphoid cells lacked VEGF and
      receptor expression. Foci of abnormal localized immature myeloid precursors
      (ALIP) co-expressed VEGF and Flt-1 receptor, suggesting autocrine cytokine
      interaction. Antibody neutralization of VEGF inhibited colony-forming unit (CFU)
      leukemia formation in 9 of 15 CMML and RAEB-t patient specimens, whereas VEGF
      stimulated leukemia colony formation in 12 patients. Neutralization of VEGF
      activity suppressed the generation of tumor necrosis factor-alpha and interleukin
      1beta from MDS BM-mononuclear cells and BM-stroma and promoted the formation of
      CFU-GEMM and burst-forming unit-erythroid in methylcellulose cultures. These
      findings indicate that autocrine production of VEGF may contribute to leukemia
      progenitor self-renewal and inflammatory cytokine elaboration in CMML and MDS and
      thus provide a biologic rationale for ALIP and its adverse prognostic relevance
      in high-risk MDS.

PMID- 11222391
TI  - Induction of myeloproliferative disease in mice by tyrosine kinase fusion
      oncogenes does not require granulocyte-macrophage colony-stimulating factor or
      interleukin-3.
AB  - Tyrosine kinase fusion oncogenes that occur as a result of chromosomal
      translocations have been shown to activate proliferative and antiapoptotic
      pathways in leukemic cells, but the importance of autocrine and paracrine
      expression of hematopoietic cytokines in leukemia pathogenesis is not understood.
      Evidence that leukemic transformation may be, at least in part, cytokine
      dependent includes data from primary human leukemia cells, cell culture
      experiments, and murine models of leukemia. This report demonstrates that
      interleukin (IL)-3 plasma levels are elevated in myeloproliferative disease (MPD)
      caused by the TEL/tyrosine kinase fusions TEL/platelet-derived growth factor beta
      receptor (PDGFbetaR), TEL/Janus kinase 2 (JAK2), and TEL/neurotrophin-3 receptor
      (TRKC). Plasma granulocyte-macrophage colony-stimulating factor (GM-CSF) levels
      were elevated by TEL/PDGFbetaR and TEL/JAK2. However, all of the fusions tested
      efficiently induced MPD in mice genetically deficient for both GM-CSF and IL-3,
      demonstrating that these cytokines are not necessary for the development of
      disease in this model system. Furthermore, in experiments using normal marrow
      transduced with TEL/PDGFbetaR retrovirus mixed with marrow transduced with an
      enhanced green fluorescent protein (EGFP) retrovirus, the MPD induced in these
      mice demonstrated minimal stimulation of normal myelopoiesis by the TEL/PDGFbetaR
      expressing cells. In contrast, recipients of mixed GM-CSF-transduced and EGFP
      transduced marrow exhibited significant paracrine expansion of EGFP-expressing
      cells. Collectively, these data demonstrate that, although cytokine levels are
      elevated in murine bone marrow transplant models of leukemia using tyrosine
      kinase fusion oncogenes, GM-CSF and IL-3 are not required for myeloproliferation
      by any of the oncogenes tested.

PMID- 11222392
TI  - Interleukin 3 and granulocyte-macrophage colony-stimulating factor are not
      required for induction of chronic myeloid leukemia-like myeloproliferative
      disease in mice by BCR/ABL.
AB  - Primitive hematopoietic progenitors from some patients with Philadelphia
      chromosome (Ph)-positive chronic myeloid leukemia (CML) express aberrant
      transcripts for interleukin 3 (IL-3) and granulocyte colony-stimulating factor (G
      CSF), and exhibit autonomous proliferation in serum-free cultures that is
      inhibited by anti-IL-3 and anti-IL-3 receptor antibodies. Expression of the
      product of the Ph chromosome, the BCR/ABL oncogene, in mice by retroviral bone
      marrow transduction and transplantation induces CML-like leukemia, and some
      leukemic mice have increased circulating IL-3, and perhaps granulocyte-macrophage
      colony-stimulating factor (GM-CSF). These observations raise the possibility of
      autocrine or paracrine cytokine production in the pathogenesis of human CML. Mice
      with homozygous inactivation of the Il-3 gene, the Gm-csf gene, or both, were
      used to test the requirement for these cytokines for induction of CML-like
      disease by BCR/ABL. Neither IL-3 nor GM-CSF was required in donor, recipient, or
      both for induction of CML-like leukemia by p210 BCR/ABL. Use of novel mice
      deficient in both IL-3 and GM-CSF demonstrated that the lack of effect on
      leukemogenesis was not due to redundancy between these hematopoietic growth
      factors. Analysis of cytokine levels in leukemic mice where either donor or
      recipient was Il-3(-/-) indicated that the increased IL-3 originated from the
      recipient, suggestive of a host reaction to the disease. These results
      demonstrate that IL-3 and GM-CSF are not required for BCR/ABL-induced CML-like
      leukemia in mice and suggest that autocrine production of IL-3 does not play a
      role in established chronic phase CML in humans.

PMID- 11222393
TI  - Treatment with NS3623, a novel Cl-conductance blocker, ameliorates erythrocyte
      dehydration in transgenic SAD mice: a possible new therapeutic approach for
      sickle cell disease.
AB  - The dehydration of sickle red blood cells (RBCs) through the Ca-activated K
      channel depends on the parallel movement of Cl ions. To study whether Cl
      conductance block might prevent dehydration of sickle RBCs, a novel Cl
      conductance inhibitor (NS3623) was characterized in vitro using RBCs from healthy
      donors and sickle cell patients and in vivo using normal mice and a transgenic
      mouse model of sickle cell disease (SAD mice). In vitro, NS3623 reversibly
      blocked human RBC Cl-conductance (g(Cl)) with an IC(50) value of 210 nmol/L and a
      maximal block of 95%. In vivo, NS3623 inhibited RBC g(Cl) after oral
      administration to normal mice (ED(50) = 25 mg/kg). Although g(Cl), at a single
      dose of 100 mg/kg, was still 70% inhibited 5 hours after dosing, the inhibition
      disappeared after 24 hours. Repeated administration of 100 mg/kg twice a day for
      10 days caused no adverse effects; therefore, this regimen was chosen as the
      highest dosing for the SAD mice. SAD mice were treated for 3 weeks with 2 daily
      administrations of 10, 35, and 100 mg/kg NS3623, respectively. The hematocrit
      increased, and the mean corpuscular hemoglobin concentration decreased in all
      groups with a concomitant increase in the intracellular cation content. A loss of
      the densest red cell population was observed in conjunction with a shift from a
      high proportion of sickled to well-hydrated discoid erythrocytes, with some
      echinocytes present at the highest dosage. These data indicate feasibility for
      the potential use of Cl-conductance blockers to treat human sickle cell disease.

PMID- 11222394
TI  - Factors affecting thymic function after allogeneic hematopoietic stem cell
      transplantation.
AB  - Hematopoietic stem cell transplantation (HSCT) is followed by profound
      immunodeficiency. Thymic function is necessary for de novo generation of T cells
      after HSCT. Circulating CD45RA(+) naive T-cell levels are predictive of antigen
      specific T-cell responses in the absence of graft-versus-host disease (GVHD).
      These T cells may not represent recent thymic emigrants, since naive T cells may
      maintain this phenotype if not antigen-activated. To accurately measure thymic
      output after HSCT and determine the factors that influence thymic function, T
      cell receptor excision circles (TRECs) were examined in CD4(+) and CD8(+) cells
      from a cross-section of patients following HSCT. TREC levels rose weeks after
      HSCT and could be detected in patients 6 years after HSCT. TREC levels correlated
      with the frequency of phenotypically naive T cells, indicating that such cells
      were not expanded progeny of naive T cells present in the donor graft. Chronic
      GVHD was the most important factor that predicted low TREC levels even years
      after HSCT. Patients with a history of resolved GVHD had decreased numbers of
      TREC, compared with those with no GVHD. Because few adults had no history of
      GVHD, it was not possible to determine whether age alone inversely correlated
      with TREC levels. Recipients of cord blood grafts had no evidence of decreased
      TREC induced by immunosuppressive prophylaxis drugs. Compared with unrelated
      donor grafts, recipients of matched sibling grafts had higher TREC levels.
      Collectively, these data suggest that thymopoiesis is inhibited by GVHD. Larger
      studies will be needed to determine the independent contributions of age and
      preparative regimen to post-transplant thymopoietic capacity.

PMID- 11222395
TI  - Posttransplantation lymphoproliferative disease in miniature swine after
      allogeneic hematopoietic cell transplantation: similarity to human PTLD and
      association with a porcine gammaherpesvirus.
AB  - Posttransplantation lymphoproliferative disease (PTLD) is a major complication of
      current clinical transplantation regimens. The lack of a reproducible large
      animal model of PTLD has limited progress in understanding the pathogenesis of
      and in developing therapy for this clinically important disease. This study found
      a high incidence of PTLD in miniature swine undergoing allogeneic hematopoietic
      stem cell transplantation and characterized this disease in swine. Two days
      before allogeneic peripheral blood stem cell transplantation, miniature swine
      were conditioned with thymic irradiation and in vivo T-cell depletion. Animals
      received cyclosporine daily beginning 1 day before transplantation and continuing
      for 30 to 60 days. Flow cytometry and histologic examination were performed to
      determine the cell type involved in lymphoproliferation. Polymerase chain
      reaction was developed to detect and determine the level of porcine
      gammaherpesvirus in involved lymph node tissue. PTLD in swine is morphologically
      and histologically similar to that observed in human allograft recipients. Nine
      of 21 animals developed a B-cell lymphoproliferation involving peripheral blood
      (9 of 9), tonsils, and lymph nodes (7 of 9) from 21 to 48 days after
      transplantation. Six of 9 animals died of PTLD and 3 of 9 recovered after
      reduction of immunosuppression. A novel porcine gammaherpesvirus was identified
      in involved tissues. Miniature swine provide a genetically defined large-animal
      model of PTLD with many characteristics similar to human PTLD. The availability
      of this reproducible large-animal model of PTLD may facilitate the development
      and testing of diagnostic and therapeutic approaches for prevention or treatment
      of PTLD in the clinical setting.

PMID- 11222396
TI  - In vitro tumor-pulsed or in vivo Flt3 ligand-generated dendritic cells provide
      protection against acute myelogenous leukemia in nontransplanted or syngeneic
      bone marrow-transplanted mice.
AB  - To determine whether immune stimulation could reduce acute myelogenous leukemia
      (AML) lethality, dendritic cells (DCs) were pulsed with AML antigens and used as
      vaccines or generated in vivo by Flt3 ligand (Flt3L), a potent stimulator of DC
      and natural killer (NK) cell generation. Mice were then challenged with AML
      cells. The total number of splenic anti-AML cytotoxic T-lymphocyte precursors
      (CTLPs) present at the time of challenge was increased 1.9-fold and 16.4-fold by
      Flt3L or DC tumor vaccines, respectively. As compared with the 0% survival of
      controls, 63% or more of recipients of pulsed DCs or Flt3L survived long term.
      Mice given AML cells prior to DC vaccines or Flt3L had only a slight survival
      advantage versus non-treated controls. NK cells or NK cells and T cells were
      found to be involved in the antitumor responses of Flt3L or DCs, respectively. DC
      vaccines lead to long-term memory responses but Flt3L does not. Syngeneic bone
      marrow transplantation (BMT) recipients were analyzed beginning 2 months post
      BMT. In contrast to the uniform lethality in BMT controls given AML cells,
      recipients of either Flt3L or DC vaccines had a significant increase in survival.
      The total number of splenic anti-AML CTLPs at the time of AML challenge in BMT
      controls was 40% of concurrently analyzed non-BMT controls. Flt3L or DC vaccines
      increased the total anti-AML CTLPs 1.4-fold and 6.8-fold, respectively. Neither
      approach was successful when initiated after AML challenge. It was concluded that
      DC vaccines and Flt3L administration can enhance an AML response in non
      transplanted or syngeneic BMT mice but only when initiated prior to AML
      progression.

PMID- 11222397
TI  - Defective antifungal T-helper 1 (TH1) immunity in a murine model of allogeneic T
      cell-depleted bone marrow transplantation and its restoration by treatment with
      TH2 cytokine antagonists.
AB  - Patients undergoing full haplotype-mismatched hematopoietic transplantations may
      experience severe intractable invasive fungal infections. To verify whether an
      imbalanced production of T-helper 1 (TH1) and TH2 cytokines may be responsible
      for susceptibility to fungal infections, C3H/HeJ (H-2(k)) recipient mice were
      lethally irradiated, received transplantations with T-cell-depleted allogeneic
      bone marrow (BM) cells from mice of H-2(d) haplotype, and were infected with
      Candida albicans. At different time-points after transplantation, mice were
      assessed for pattern of TH cytokine production and susceptibility to infection.
      The results show that a long-term, donor-type chimerism was achieved as early as
      2 weeks after BM transplantation (BMT), at the time when high-level production of
      TH2 cytokines (interleukin-4 [IL-4] and IL-10) and impaired production of TH1
      cytokines (interferon-gamma [IFN-gamma] and IL-12] were observed. At this time,
      mice were highly susceptible to both disseminated and mucosal infections, as
      indicated by decreased survival, uncontrolled fungal growth, and failure to
      develop protective TH1 immunity. However, a predominant production of TH1
      cytokines was observed by week 5 after BMT, at the time when mice developed donor
      type protective TH1 responses and were resistant to infections. Therapeutic
      ablation of IL-4 or IL-10 greatly increased resistance to candidiasis. These
      results indicate that a dysregulated production of TH cytokines occurs in mice
      undergoing T-cell-depleted allogeneic BMT. The transient predominant production
      of TH2 cytokines over that of IL-12 impaired the ability of mice to develop
      antifungal TH1 resistance, an activity that could be efficiently restored upon
      treatment with TH2 cytokine antagonists.

PMID- 11222398
TI  - IL-7 increases both thymic-dependent and thymic-independent T-cell regeneration
      after bone marrow transplantation.
AB  - Thymic-dependent differentiation of bone marrow (BM)-derived progenitors and
      thymic-independent antigen-driven peripheral expansion of mature T cells
      represent the 2 primary pathways for T-cell regeneration. These pathways are
      interregulated such that peripheral T-cell expansion is increased in
      thymectomized versus thymus-bearing hosts after bone marrow transplantation
      (BMT). This study shows that this interregulation is due to competition between
      progeny of these 2 pathways because depletion of thymic progeny leads to
      increased peripheral expansion in thymus-bearing hosts. To test the hypothesis
      that competition for growth factors modulates the magnitude of antigen-driven
      peripheral expansion during immune reconstitution in vivo, a variety of T-cell
      active cytokines were administered after BMT. Of the cytokines (interleukins)
      tested (IL-3, IL-12, IL-6, IL-2, and IL-7), IL-2 modestly increased peripheral
      expansion in the face of increasing numbers of thymic emigrants, whereas IL-7
      potently accomplished this. This report also demonstrates that the beneficial
      effect of IL-7 on immune reconstitution is related to both increases in
      thymopoiesis as well as a direct increase in the magnitude of antigen-driven
      peripheral expansion. Therefore, the administration of exogenous IL-7, and to a
      lesser extent IL-2, abrogates the down-regulation in antigen-driven peripheral
      expansion that occurs in thymus-bearing hosts after BMT. These results suggest
      that one mechanism by which T-cell-depleted hosts may support antigen-driven T
      cell expansion in vivo is via an increased availability of T-cell-active
      cytokines to support clonal expansion.

PMID- 11222399
TI  - Nonablative neonatal marrow transplantation attenuates functional and physical
      defects of beta-glucuronidase deficiency.
AB  - The toxicity of preparative regimens render neonatal bone marrow transplantation
      (BMT) for progressive childhood diseases a controversial treatment. Ablative BMT
      in neonatal mice with or without the lysosomal storage disease
      mucopolysaccharidosis type VII (MPS VII) show high morbidity and developmental
      disruption of both brain and bone structure. In this investigation, BMT was
      performed with a high dose of congenic, normal bone marrow into nonablated
      newborn mice. Recipients had lifelong, multilineage, peripheral blood chimerism
      with the donor beta-glucuronidase-positive (GUS(+)) cells that was both well
      tolerated and therapeutic. Three daily injections of normal adult marrow
      increased the average life span by at least 6 months and corrected the functional
      breeding deficits typical of the MPS VII mice. Twelve months after injection,
      several structural features of femurs were more like that of normal mice than of
      untreated MPS VII mice. Periosteal circumference and bone cortical thickness were
      significantly improved in males and cortical density did not differ significantly
      from values in normal females. Significant reduction of lysosomal
      glycosaminoglycan storage corresponded directly with GUS enzyme activity and
      percentage of histochemically GUS(+) cells in visceral organs and hematopoietic
      tissues such as thymus, spleen, peripheral blood, and bone marrow. By all
      criteria tested, BMT into neonatal MPS VII mice in the absence of any preparative
      regimen is a successful therapy.

PMID- 11222400
TI  - The interphase microtubule damage checkpoint defines an S-phase commitment point
      and does not require p21(waf-1).
AB  - Cell cycle checkpoints ensure orderly progression of events during cell division.
      A microtubule damage (MTD)-induced checkpoint has been described in G(1) phase of
      the cell cycle (G(1)MTC) for which little is known. The present study shows that
      the G(1)MTC is intact in activated T lymphocytes from mice with the p21(waf-1)
      gene deleted. However, p21(waf-1) gene deletion does affect the ratio of cells
      that arrest at the G(1)MTC and the spindle checkpoint after MTD. The G(1)MTC
      arrests T lymphocytes in G(1) prior to cdc2 up-regulation and prior to G(1)
      arrest by p21(waf-1). Once cells have progressed past the G(1)MTC, they are
      committed to chromosome replication and metaphase progression, even with extreme
      MTD. The G(1)MTC is also present in a human myeloid cell line deficient in
      p21(waf-1) gene expression. The p21-independent G(1)MTC may be important in
      cellular responses to MTD such as those induced by drugs used to treat cancer.

PMID- 11222401
TI  - Sperm protein 17 is a novel cancer-testis antigen in multiple myeloma.
AB  - Various studies have demonstrated the aberrant expression of normal testicular
      proteins in neoplastic cells. These proteins collectively form the new class of
      tumor antigens called cancer-testis (CT) antigens. Their selective normal tissue
      expression makes them ideal antigens for immune targeting of the malignant
      disease. In this study, the expression of a spermatozoa protein, Sp17, in
      multiple myeloma was investigated. It was found that Sp17 is detectable in tumor
      cells from 12 of 47 (26%) myeloma patients. Reverse transcription polymerase
      chain reaction (RT-PCR) and Western blot analysis detected Sp17 transcripts and
      proteins, respectively. Northern blot analysis and RT-PCR demonstrated that Sp17
      transcripts were detected only in normal testis, supporting its tissue
      specificity. Since a high proportion of normal individuals develop antibodies
      against Sp17 following vasectomy, Sp17 is likely to be a highly immunogenic
      protein in vivo. Sp17 is therefore a novel member of the CT antigen family and
      should be an ideal target for immunotherapy of multiple myeloma.

PMID- 11222402
TI  - The diversity of rearranged immunoglobulin heavy chain variable region genes in
      peripheral blood B cells of preterm infants is restricted by short third
      complementarity-determining regions but not by limited gene segment usage.
AB  - The immunoglobulin diversity is restricted in fetal liver B cells. This study
      examined whether peripheral blood B cells of extremely preterm infants show
      similar restrictions (overrepresentation of some gene segments, short third
      complementarity-determining regions [CDR3]). DNA of rearranged immunoglobulin
      heavy chain genes was amplified by polymerase chain reaction, cloned, and
      sequenced. A total of 417 sequences were analyzed from 6 preterm infants (25-28
      weeks of gestation), 6 term infants, and 6 adults. Gene segments from the entire
      V(H) and D(H) gene locus were rearranged in preterm infants, even though the
      D(H)7-27 segment was overrepresented (17% of rearrangements) compared to term
      infants (7%) and adults (2%). CDR3 was shorter in preterm infants (40 +/- 10
      nucleotides) than in term infants (44 +/- 12) and adults (48 +/- 14) (P <.001)
      due to shorter N regions. Somatic mutations were exclusively found in term
      neonates and adults (mutational frequency 0.8% and 1.8%). We conclude that
      preterm infants have no limitations in gene segment usage, whereas the diversity
      of CDR3 is restricted throughout gestation.

PMID- 11222403
TI  - Torsades de pointes in 3 patients with leukemia treated with arsenic trioxide.
AB  - Arsenic trioxide is used in clinical trials in the treatment of relapsed and
      resistant cases of acute promyelocytic leukemia. Adverse effects from arsenic in
      these studies have been multisystemic. Arsenic is known to cause corrected QT
      interval prolongation and T-wave changes, but the potential for serious
      ventricular arrhythmias is less well understood. Torsades de pointes, a form of
      ventricular tachycardia, has been reported with arsenic poisoning but not at
      therapeutic doses used in protocols for hematologic malignancies. We describe 3
      patients in whom this arrhythmia developed while they were treated with arsenic
      trioxide. Early recognition of the arrhythmia or correction of contributory
      factors is important because arsenic induced ventricular arrhythmias are known to
      be resistant to most chemical methods and electrical cardioversion.

PMID- 11222404
TI  - Prenatal diagnoses of sex chromosome conditions.

PMID- 11222405
TI  - Undermining data privacy in health information.

PMID- 11222406
TI  - Physical health of people with severe mental illness.

PMID- 11222407
TI  - Towards a global definition of patient centred care.

PMID- 11222408
TI  - Wider lessons of the pulmonary artery catheter trial.

PMID- 11222409
TI  - Drug companies sue South African government over generics.

PMID- 11222410
TI  - The failings of NICE. Latest decision on zanamivir will not end postcode
      prescribing.

PMID- 11222411
TI  - Medical research under threat after Alder Hey scandal.

PMID- 11222412
TI  - Complaints against UK doctors rise 50%.

PMID- 11222413
TI  - Alcohol and drug misuse sweeping world, says WHO.

PMID- 11222414
TI  - US employer agrees to stop genetic testing.

PMID- 11222415
TI  - India plans massive hospital rebuilding after earthquake.

PMID- 11222416
TI  - Blair unable to fulfil pledge on health spending, says analysis.

PMID- 11222417
TI  - Dutch smokers seek tobacco damages.

PMID- 11222418
TI  - Antismoking drug comes under scrutiny after deaths.

PMID- 11222419
TI  - Therapeutic nursing or unblocking beds? A randomised controlled trial of a post
      acute intermediate care unit.
AB  - OBJECTIVES: To compare post-acute intermediate care in an inpatient nurse-led
      unit with conventional post-acute care on general medical wards of an acute
      hospital and to examine the model of care in a nurse-led unit. DESIGN: Randomised
      controlled trial with six month follow up. SETTING: Urban teaching hospital and
      surrounding area, including nine community hospitals. PARTICIPANTS: 238 patients
      accepted for admission to nurse-led unit. INTERVENTIONS: Care in nurse-led unit
      or usual post-acute care. MAIN OUTCOME MEASURES: Patients' length of stay,
      functional status, subsequent move to more dependent living arrangement. RESULTS:
      Inpatient length of stay was significantly longer in the nurse-led unit than in
      general medical wards (14.3 days longer (95% confidence interval 7.8 to 20.7)),
      but this difference became non-significant when transfers to community hospitals
      were included in the measure of initial length of stay (4.5 days longer (-3.6 to
      12.5)). No differences were observed in mortality, functional status, or living
      arrangements at any time. Patients in the nurse-led unit received significantly
      fewer minor medical investigations and, after controlling for length of stay,
      significantly fewer major reviews, tests, or drug changes. CONCLUSIONS: The nurse
      led unit seemed to be a safe alternative to conventional management, but a full
      accounting of such units' place in the local continuum of care and the costs
      associated with acute hospitals managing post-acute patients is needed if nurse
      led units are to become an effective part of the government's recent commitment
      to intermediate care.

PMID- 11222420
TI  - Mumps, measles, and rubella vaccine and the incidence of autism recorded by
      general practitioners: a time trend analysis.
AB  - OBJECTIVE: To estimate changes in the risk of autism and assess the relation of
      autism to the mumps, measles, and rubella (MMR) vaccine. DESIGN: Time trend
      analysis of data from the UK general practice research database (GPRD). SETTING:
      General practices in the United Kingdom. SUBJECTS: Children aged 12 years or
      younger diagnosed with autism 1988-99, with further analysis of boys aged 2 to 5
      years born 1988-93. MAIN OUTCOME MEASURES: Annual and age specific incidence for
      first recorded diagnoses of autism (that is, when the diagnosis of autism was
      first recorded) in the children aged 12 years or younger; annual, birth cohort
      specific risk of autism diagnosed in the 2 to 5 year old boys; coverage
      (prevalence) of MMR vaccination in the same birth cohorts. RESULTS: The incidence
      of newly diagnosed autism increased sevenfold, from 0.3 per 10 000 person years
      in 1988 to 2.1 per 10 000 person years in 1999. The peak incidence was among 3
      and 4 year olds, and 83% (254/305) of cases were boys. In an annual birth cohort
      analysis of 114 boys born in 1988-93, the risk of autism in 2 to 5 year old boys
      increased nearly fourfold over time, from 8 (95% confidence interval 4 to 14) per
      10 000 for boys born in 1988 to 29 (20 to 43) per 10 000 for boys born in 1993.
      For the same annual birth cohorts the prevalence of MMR vaccination was over 95%.
      CONCLUSIONS: Because the incidence of autism among 2 to 5 year olds increased
      markedly among boys born in each year separately from 1988 to 1993 while MMR
      vaccine coverage was over 95% for successive annual birth cohorts, the data
      provide evidence that no correlation exists between the prevalence of MMR
      vaccination and the rapid increase in the risk of autism over time. The
      explanation for the marked increase in risk of the diagnosis of autism in the
      past decade remains uncertain.

PMID- 11222421
TI  - What parents are told after prenatal diagnosis of a sex chromosome abnormality:
      interview and questionnaire study.
AB  - OBJECTIVE: To investigate how the prenatal diagnosis of a sex chromosome anomaly
      is first communicated to parents. DESIGN: Health professionals were interviewed
      by telephone and the conversation was taped; parents were sent questionnaires at
      1 month after diagnosis and those who responded were sent another at 6 months.
      PARTICIPANTS: 29 health professionals who had recently informed parents that a
      sex chromosome anomaly had been identified in an apparently anatomically normal,
      viable fetus. 23 mothers and partners who had been informed of such a diagnosis.
      MAIN OUTCOME MEASURES: Health professionals' knowledge about sex chromosome
      anomalies and parents' responses to information provided by health professionals.
      RESULTS: Analysis of the telephone interviews identified great variation in what
      different healthcare professionals know, think, and say about the same sex
      chromosome anomaly. The small numbers and the low response rate for the
      questionnaire (39% for women and 30% for men) meant that statistical analysis was
      not appropriate. CONCLUSIONS: It is essential for obstetric units to have an
      established protocol for giving results and for all staff who communicate results
      to parents to have accurate, up to date information about the condition
      identified.

PMID- 11222422
TI  - Mortality of third generation Irish people living in England and Wales:
      longitudinal study.

PMID- 11222424
TI  - Management of patients in fast track surgery.

PMID- 11222423
TI  - Preferences of patients for patient centred approach to consultation in primary
      care: observational study.
AB  - OBJECTIVE: To identify patient's preferences for patient centred consultation in
      general practice. DESIGN: Questionnaire study. SETTING: Consecutive patients in
      the waiting room of three doctors' surgeries. MAIN OUTCOME MEASURES: Key domains
      of patient centredness from the patient perspective. Predictors of preferences
      for patient centredness, a prescription, and examination. RESULTS: 865 patients
      participated: 824 (95%) returned the pre-consultation questionnaire and were
      similar in demographic characteristic to national samples. Factor analysis
      identified three domains of patient preferences: communication (agreed with by 88
      99%), partnership (77-87%), and health promotion (85-89%). Fewer wanted an
      examination (63%), and only a quarter wanted a prescription. As desire for a
      prescription was modestly associated with desire for good communication (odds
      ratio 1.20; 95% confidence interval 0.85 to 1.69), partnership (1.46; 1.01 to
      2.09), and health promotion (1.61; 1.12 to 2.31) this study may have
      underestimated preferences for patient centredness compared with populations with
      stronger preferences for a prescription. Patients who strongly wanted good
      communication were more likely to feel unwell (very, moderately, and slightly
      unwell; odds ratios 1, 0.56, 0.39 respectively, z trend P<0.001), be high
      attenders (1.70; 1.18 to 2.44), and have no paid work (1.84; 1.21 to 2.79).
      Strongly wanting partnership was also related to feeling unwell, worrying about
      the problem, high attendance, and no paid work; and health promotion to high
      attendance and worry. CONCLUSION: Patients in primary care strongly want a
      patient centred approach, with communication, partnership, and health promotion.
      Doctors should be sensitive to patients who have a strong preference for patient
      centredness-those vulnerable either psychosocially or because they are feeling
      unwell.

PMID- 11222426
TI  - ABC of diseases of liver, pancreas, and biliary system.

PMID- 11222427
TI  - Lesson of the week: Splenic trauma complicating cardiopulmonary resuscitation.

PMID- 11222428
TI  - Depression in developing countries: lessons from Zimbabwe.

PMID- 11222429
TI  - What brings asylum seekers to the United Kingdom?

PMID- 11222430
TI  - Comparison of St John's Wort and imipramine. Remission is important outcome.

PMID- 11222431
TI  - The failings of NICE. NICE's guidance suggests using rosiglitazone in type 2
      diabetes later than is ideal.

PMID- 11222432
TI  - Comparison of St John's Wort and imipramine. Study design casts doubt on value of
      St John's wort in treating depression.

PMID- 11222433
TI  - Foundation is helping carers to reduce risk of sudden infant death syndrome.

PMID- 11222434
TI  - Comparison of St John's Wort and imipramine. Finding must be treated with
      caution.

PMID- 11222435
TI  - Needle length and incidence of local reactions to immunisation. Is there a real
      benefit for the child?

PMID- 11222436
TI  - Increasing use of abbreviations is unacceptable.

PMID- 11222437
TI  - The failings of NICE. Reply from chairman of NICE.

PMID- 11222438
TI  - The failings of NICE. Editor's choice of acronym for new NICE is Punjabi for
      thief.

PMID- 11222439
TI  - The failings of NICE. NICE and evidence based medicine are not really compatible.

PMID- 11222440
TI  - Needle length and incidence of local reactions to immunisation. How quickly can
      research change practice?

PMID- 11222441
TI  - The failings of NICE. Rationing is a respectable word for a disgraceful retreat.

PMID- 11222442
TI  - The failings of NICE. Doctors treating patients with multiple sclerosis will lose
      confidence in NICE.

PMID- 11222443
TI  - The failings of NICE. "Spinning" is not nice.

PMID- 11222444
TI  - Needle length and incidence of local reactions to immunisation. Further research
      is needed before practice is changed.

PMID- 11222445
TI  - Risk stratification and carotid surgery: new technology but old trials.

PMID- 11222446
TI  - Severely impaired cerebrovascular reactivity predicts stroke and TIA risk in
      patients with carotid artery stenosis and occlusion.
AB  - Cross-sectional studies suggest that impaired cerebral haemodynamics is
      associated with symptomatic status in patients with carotid stenosis and
      occlusion, but there is relatively little prospective data confirming this
      association. Transcranial Doppler ultrasonography was used to determine the
      reactivity of the middle cerebral artery to 8% carbon dioxide in air in 107
      patients with either carotid occlusion (n = 48) or asymptomatic carotid stenosis
      (n = 59). Subjects were followed prospectively until stroke, transient ischaemic
      attack (TIA), death or study end. Mean duration of follow-up was 635 days. No
      patients dropped out due to operation before an end-point was reached, or were
      lost to follow-up. There were 11 ipsilateral ischaemic events during follow-up
      (six strokes, five TIAs). Exhausted ipsilateral middle cerebral artery reactivity
      (>20% increase in ipsilateral middle cerebral flow velocity in response to 8%
      carbon dioxide) predicted ipsilateral stroke and TIA risk in the whole group (P:
      < 0.00001) and in the carotid occlusion (P: = 0.019) and carotid stenosis (P: =
      0.015) groups alone. It also predicted the risk of ipsilateral stroke alone in
      all three groups. Cox regression was performed, controlling for age, gender,
      hypertension, diabetes, smoking, ipsilateral CT infarct, degree of contralateral
      stenosis and the presence of ipsilateral stenosis versus occlusion. Exhausted
      reactivity remained an independent predictor of ipsilateral stroke and TIA (odds
      ratio 14.4, 95% confidence interval 2.63-78.74, P: = 0.0021). In contrast, the
      pulsatility index of the middle cerebral artery was a poor predictor of the risk
      of stroke. Reactivity to 6% carbon dioxide also predicted the risk of stroke and
      TIA, but slightly less effectively than reactivity to 8% carbon dioxide. Severely
      reduced cerebrovascular reactivity predicts the risk of ipsilateral stroke and
      TIA in patients with carotid occlusion, and to a lesser extent in asymptomatic
      carotid stenosis. Particularly in the former group, a study is required to
      determine whether revascularization reduces the risk of stroke in patients with
      exhausted reactivity.

PMID- 11222447
TI  - Long-term remyelination after optic neuritis: A 2-year visual evoked potential
      and psychophysical serial study.
AB  - Thirty-one patients were followed-up, at 3-month intervals for the first year and
      at 6-month intervals for the second year, after an episode of optic neuritis. The
      object was to confirm previous evidence for a progressive shortening of visual
      evoked potential (VEP) latencies and to determine whether this is associated with
      any change in the clinical ocular examination, visual fields or contrast
      sensitivity. VEP latencies were found to decrease significantly during both the
      first and (less strikingly) the second year, the most marked changes occurring
      between 3 and 6 months. Contrast sensitivity improved during the first 9 months,
      but subsequently tended (non-significantly) to deteriorate. A similarly transient
      improvement in central visual field sensitivity was seen in a subgroup of
      patients with clinically overt multiple sclerosis. In the data from the acutely
      unaffected fellow eyes, no significant changes in VEP parameters or functional
      indices were observed. The findings extend those of a previous study which showed
      significant shortening of VEP latencies between 6 months and 3 years without
      significant functional improvement. Over this period, a significant prolongation
      of VEP latencies occurred in the asymptomatic fellow eye, accompanied by contrast
      sensitivity deterioration. Taken in conjunction, the two studies suggest that
      recovery processes involving remyelination or, possibly, ion channel
      reorganization proceed for at least 2 years. The concurrent effects of insidious
      demyelination and/or axonal degeneration (also occurring in the fellow optic
      nerve) are initially masked by the recovery process, but gradually become more
      evident. The functional benefits of the long-term recovery process are relatively
      minor and are usually reversed within a few years. Nevertheless, it is suggested
      that long-term remyelination may perform an important role in protecting
      demyelinated axons from degeneration. Understanding the factors which promote
      long-term remyelination may have significant implications for therapy in multiple
      sclerosis.

PMID- 11222448
TI  - Two subsets of dendritic cells are present in human cerebrospinal fluid.
AB  - Little is known about the presence of dendritic cells in the human CNS. To
      investigate the occurrence of dendritic cells in the CSF, paired blood/CSF
      samples from patients with multiple sclerosis, acute optic neuritis, Lyme
      neuroborreliosis, other inflammatory neurological diseases and non-inflammatory
      neurological diseases were examined using flow cytometry. Almost all CSF samples
      contained myeloid (lin-CD11c+HLA-DR++CD123(dim)) and plasmacytoid (lin-CD11c-HLA
      DR+CD123(high)) dendritic cells. In non-inflammatory neurological diseases,
      dendritic cells of either subset only constituted up to 1% of CSF mononuclear
      cells. Myeloid CSF dendritic cells were elevated in optic neuritis,
      neuroborreliosis and other inflammatory neurological disorders, while
      plasmacytoid dendritic cells were elevated in all neuroinflammatory conditions
      studied, with especially high numbers in neuroborreliosis. Numbers of CSF
      dendritic cells correlated with the common parameters of CNS inflammation. The
      myeloid dendritic cells in CSF expressed higher levels of HLA-DR, CD86, CD80 and
      CD40 than those in blood, whereas expression of these molecules by plasmacytoid
      dendritic cells was equal in blood and CSF. Both CSF and blood dendritic cells
      expressed the chemokine receptor CCR5. This is the first demonstration that
      dendritic cells are present in human CSF and that plasmacytoid dendritic cells
      are present in a non-lymphoid compartment. Myeloid and plasmacytoid dendritic
      cells in CSF may contribute to orchestration of the local immune responses.

PMID- 11222449
TI  - Matrix metalloproteinases and tissue inhibitors of metalloproteinases in
      cerebrospinal fluid differ in multiple sclerosis and Devic's neuromyelitis
      optica.
AB  - Matrix metalloproteinases (MMPs) are increased in the CSF of patients with
      multiple sclerosis. Devic's neuromyelitis optica (DNO) is a demyelinating
      syndrome that involves the optic nerve and cervical cord but differs
      pathologically from multiple sclerosis. Therefore, we hypothesized that the type
      of inflammatory reaction that causes MMPs to be elevated in multiple sclerosis
      would be absent in patients with DNO. CSF was collected from 23 patients with
      relapsing-remitting or secondary progressive multiple sclerosis, all of whom were
      experiencing acute symptoms, from seven patients with DNO, and from seven normal
      volunteers. Diagnoses were made according to current criteria on the basis of
      clinical manifestations, imaging results and CSF studies. IgG synthesis was
      increased in the CSF of multiple sclerosis patients but not in that of DNO
      patients. Zymography, reverse zymography and ELISA (enzyme-linked immunosorbent
      assay) were used to measure gelatinase A (MMP-2), gelatinase B (MMP-9) and tissue
      inhibitors of metalloproteinases (TIMPs). Zymograms showed that multiple
      sclerosis patients had elevated MMP-9 compared with DNO patients and controls (P:
      < 0.05). TIMP-1 and TIMP-2 levels were similar in all three groups. We conclude
      that multiple sclerosis patients have higher MMP-9 levels in the CSF than
      patients with DNO, which supports the different pathological mechanisms of these
      diseases.

PMID- 11222450
TI  - Focal autobiographical amnesia in association with transient epileptic amnesia.
AB  - Although problems with remembering significant events from the past (e.g.
      holidays, weddings, etc.) have been reported previously in patients with
      transient epileptic amnesia (TEA), to date there have been no detailed studies of
      autobiographical memory in patients with this disorder. To investigate this
      issue, a 68-year-old right-handed man (R.G.) who suffered from TEA and reported
      significant autobiographical memory problems was tested on a battery of
      neuropsychological tests of anterograde and remote memory. Tests of
      autobiographical memory revealed that R.G. was unable to evoke detailed
      autobiographical recollections from a substantial part of his life. By contrast,
      he performed well on tests of new learning and general knowledge and possessed
      good personal semantic information about his past. In summary, a distinct form of
      autobiographical amnesia, which is characterized by loss of experiential
      remembering of significant events, may be associated with TEA. It is proposed
      that the autobiographical memory deficit seen in the disorder may result from the
      progressive erasure of cortically based memory representations. This case adds to
      growing evidence for a dissociation between mechanisms subserving anterograde
      memory and those required to evoke remote episodic memories.

PMID- 11222451
TI  - The functional anatomy of single-word reading in patients with hemianopic and
      pure alexia.
AB  - We investigated single-word reading in normal subjects and patients with alexia
      following a left occipital infarct, using PET. The most posterior brain region to
      show a lateralized response was at the left occipitotemporal junction, in the
      inferior temporal gyrus. This region was activated when normal subjects, patients
      with hemianopic alexia and patients with an incomplete right homonymous
      hemianopia, but no reading deficit, viewed single words presented at increasing
      rates. This same area was damaged in a patient with pure alexia ("alexia without
      agraphia") and no hemianopia, who read words slowly using a letter-by-letter
      strategy. Although the exact level of the functional deficit is controversial,
      pure alexia is the result of an inability to map a percept of all the letters in
      a familiar letter string on to the mental representation of the whole word form.
      However, the commonest deficit associated with "pure" alexia is a right
      homonymous field defect; an impairment that may, by itself, interfere with single
      word reading because of inability to see the letters towards the end of a word.
      The relative contributions of pure and hemianopic alexia in individual patients
      needs to be assessed, as the latter has been shown to respond well to specific
      rehabilitation programmes.

PMID- 11222452
TI  - Oculopharyngeal muscular dystrophy: phenotypic and genotypic studies in a UK
      population.
AB  - Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disorder of
      late onset that commonly presents with ptosis and dysphagia. The genetic basis of
      the condition has been identified recently as a stable trinucleotide repeat
      expansion in exon 1 of the poly(A) binding protein 2 gene (PABP2), in which
      (GCG)(6) is the normal repeat length. The prevalence of OPMD is greatest in
      patients of French-Canadian origin. It is not clear if expansion repeat length is
      a reliable test in other populations. In this study, we analysed the phenotypic
      and genotypic characteristics of 31 patients with OPMD in the UK. Ptosis was the
      first reported symptom in two-thirds of the patients, and half of the subjects
      studied had evidence of ophthalmoplegia. All but one family had a pathological
      expansion in the PABP2 gene, ranging from (GCG)(8) to (GCG)(13). In contrast to
      the French-Canadian population, (GCG)(10) was almost as common as (GCG)(9),
      evidence against a strong founder effect in the UK population. There was a weak
      association between repeat length and age of disease onset. Patients with longer
      repeat lengths, such as (GCG)(13), developed severe limb weakness early in the
      disease. We were unable to detect the (GCG)(7) polymorphism in over 200 normal
      controls, suggesting that the frequency of this expansion is lower than that
      found in the French-Canadian population. One family was negative for the
      expansion. Affected members presented with the classical features of OPMD, namely
      ptosis, dysphagia and cytoplasmic inclusions on muscle biopsy, although with some
      atypical features, such as early age of onset, high serum levels of creatine
      kinase and a profound ophthalmoplegia. This family is an example of a GCG
      expansion-negative oculopharyngeal syndrome requiring further genetic
      investigation. We conclude that PABP2 analysis is a reliable non-invasive
      diagnostic test for OPMD in the UK population.

PMID- 11222453
TI  - Size perception in hemianopia and neglect.
AB  - Some debate remains as to whether underestimation of the horizontal size of
      objects in the left part of visual space is a general disturbance in spatial
      neglect. The issue is unclear because size perception may be influenced by
      factors other than neglect, e.g. visual field defects such as hemianopia. To
      disentangle these effects, we compared the performance of patients with pure
      neglect, pure hemianopia or both on the same size-comparison test. Whereas pure
      neglect was accompanied by misperception of horizontal object size, patients with
      pure hemianopia showed an even greater impairment of size perception.
      Accordingly, the area of maximum lesion overlap of these patients with impaired
      size perception was not centred around the parietotemporal cortex, which is
      typically associated with spatial neglect, but rather was found in the occipital
      lobe (Brodmann areas 17 and 18). The results suggest that spatial neglect is not
      an inevitable consequence of distorted size perception. The perceptual distortion
      of objects in the leftward parts of visual space is not sufficient to account for
      the occurrence of visuospatial neglect.

PMID- 11222454
TI  - Abnormalities of sensorimotor integration in focal dystonia: a transcranial
      magnetic stimulation study.
AB  - It has been postulated that sensorimotor integration is abnormal in dystonia. We
      investigated changes in motor cortical excitability induced by peripheral
      stimulation in patients with focal hand dystonia (12 patients with hand cramps)
      and with cervical dystonia (nine with spasmodic torticollis) compared with 16 age
      matched normal controls. Motor evoked potentials (MEP) to focal (figure-of-eight
      coil) transcranial magnetic stimulation of the hand area were recorded from the
      right abductor pollicis brevis (APB), first dorsal interosseus (FDI), flexor
      carpi radialis and extensor carpi radialis muscles. Changes of test MEP size
      following conditioning stimulation of the right median nerve (or of the index
      finger) at conditioning-test (C-T) intervals of 50, 200, 600 and 1000 ms were
      analysed. Peripheral stimulation significantly reduced test MEP size in the APB
      and FDI muscles of normal control and spasmodic torticollis patients. The
      inhibitory effect was larger upon median nerve stimulation and reached a maximum
      at the C-T interval of 200 ms. On the contrary, hand cramp patients showed a
      significant facilitation of test MEP size. This study suggests that MEP
      suppression following peripheral stimulation is defective in patients with focal
      hand dystonia. Central processing of sensory input is abnormal in dystonia and
      may contribute to increased motor cortical excitability.

PMID- 11222455
TI  - Dopamine agonist-induced dyskinesias are correlated to both firing pattern and
      frequency alterations of pallidal neurones in the MPTP-treated monkey.
AB  - Despite the importance and frequency of levodopa-induced dyskinesias, little is
      known about their causal mechanisms. In this study, electrophysiological single
      unit recordings of the neuronal activity of the globus pallidus internalis (GPi),
      the main basal ganglia output structure, and the globus pallidus externalis (GPe)
      were recorded continuously in both normal and 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine treated subhuman primates before and after the administration
      of three dopamine agonists--apomorphine (a dopaminergic mixed agonist), SKF-38393
      (a D1 partial agonist) and piribedil (a D2/D3 agonist)--at doses known to induce
      dyskinesias in the parkinsonian monkey. Changes in both the firing frequency and
      the firing pattern were analysed in relation to behavioural modifications. In
      both the normal and the parkinsonian monkey, the three agonists induced a
      decrease in the mean firing frequency of GPi neurones, although dyskinesias were
      induced only in the parkinsonian animals. In this situation, the improvement of
      parkinsonian motor abnormalities was correlated with the decrease in GPi firing
      frequency, whereas firing pattern changes were concomitant with the onset of
      dyskinesias. Moreover, firing frequency seemed to be decreased excessively during
      dyskinesias. The results indicate that the electrophysiological mechanism of
      dyskinesia involves an excessive decrease in GPi firing frequency and a
      modification of the firing pattern. However, the similarity between the induced
      decrease in firing frequency in normal and parkinsonian animals underlines the
      need for dopamine depletion in the induction of dyskinesias.

PMID- 11222456
TI  - Event-related functional magnetic resonance imaging in Parkinson's disease before
      and after levodopa.
AB  - Event-related functional MRI (fMRI) was used to study blood oxygen level
      dependent cortical signal changes associated with volitional limb movements off
      and on levodopa in Parkinson's disease. Eight patients with early stage akinetic
      Parkinson's disease and eight healthy volunteers underwent three functional
      imaging runs (high speed echo planar imaging with 600 scans/run) while performing
      paced single joystick movements in a freely chosen direction every 7-15 s. The
      non-magnetic joystick was linked to a monitoring system for on-line registration
      of performance parameters along with timing of the pacing tones and fMRI-scan
      acquisition parameters. This allowed correlation of movement onset, i.e. event
      onset, to scanning time. We repeated the scanning procedure in the Parkinson's
      disease patients when akinesia improved 30 min after oral levodopa. Compared with
      the control group, patients both off and on levodopa showed movement-related
      impaired activation in the rostral supplementary motor area and increased
      activation in primary motor cortex (M1) and the lateral premotor cortex
      bilaterally. Levodopa led to a relative normalization of the impaired activation
      in the mesial premotor cortex and decreased signal levels in M1, lateral premotor
      and superior parietal cortex. We conclude that levodopa improves impaired motor
      initiation in the supplementary motor area and decreases hyperfunction of lateral
      premotor and M1 associated with Parkinson's disease during simple volitional
      movements.

PMID- 11222457
TI  - Cortical mechanism for the visual guidance of hand grasping movements in the
      monkey: A reversible inactivation study.
AB  - Picking up an object requires two basic motor operations: reaching and grasping.
      Neurophysiological studies in monkeys have suggested that the visuomotor
      transformations necessary for these two operations are carried out by separate
      parietofrontal circuits and that, for grasping, a key role is played by a
      specific sector of the ventral premotor cortex: area F5. The aim of the present
      study was to test the validity of this hypothesis by reversibly inactivating area
      F5 in monkeys trained to grasp objects of different shape, size and orientation.
      In separate sessions, the hand field of the primary motor cortex (area F1 or area
      4) was also reversibly inactivated. The results showed that after inactivation of
      area F5 buried in the bank of the arcuate sulcus (the F5 sector where visuomotor
      neurones responding to object presentation are located), the hand shaping
      preceding grasping was markedly impaired and the hand posture was not appropriate
      for the object size and shape. The monkeys were eventually able to grasp the
      objects, but only after a series of corrections made under tactile control. With
      small inactivations the deficits concerned the contralesional hand, with larger
      inactivations the ipsilateral hand as well. In addition, there were signs of
      peripersonal neglect in the hemispace contralateral to the inactivation site.
      Following inactivation of area F5 lying on the cortical convexity (the F5 sector
      where visuomotor neurones responding to action observation, 'mirror neurones',
      are found) only a motor slowing was observed, the hand shaping being preserved.
      The inactivation of the hand field of area F1 produced a severe paralysis of
      contralateral finger movements with hypotonia. The results of this study indicate
      the crucial role of the ventral premotor cortex in visuomotor transformations for
      grasping movements. More generally, they provide strong support for the notion
      that distal and proximal movement organization relies upon distinct cortical
      circuits. Clinical data on distal movement deficits in humans are re-examined in
      the light of the present findings.

PMID- 11222458
TI  - Vascular abnormalities in reflex sympathetic dystrophy (CRPS I): mechanisms and
      diagnostic value.
AB  - Complex regional pain syndrome type I (CRPS I, formerly known as reflex
      sympathetic dystrophy) is a painful neuropathic disorder that develops after
      trauma affecting the limbs without overt nerve injury. Clinical features are
      spontaneous pain, hyperalgesia, impairment of motor function, swelling, changes
      in sweating, and vascular abnormalities. In this study, the pathophysiological
      mechanisms of vascular abnormalities were investigated. Furthermore, the
      incidence, sensitivity and specificity of side differences in skin temperature
      were defined in order to distinguish patients with definite CRPS I from patients
      with extremity pain of other origin. In 25 CRPS I patients and two control groups
      (20 healthy subjects and 15 patients with other types of extremity pain),
      cutaneous sympathetic vasoconstrictor activity was altered tonically by the use
      of controlled thermoregulation. Whole-body temperature changes were induced with
      a thermal suit in which cold or hot water circulated. The vascular reflex
      response (skin blood flow, laser Doppler flowmetry, skin temperature, infrared
      thermometry) was analysed to quantify sympathetic outflow. Measurements were
      performed during a complete thermoregulatory cycle, i.e. during the entire
      spectrum of sympathetic vasoconstrictor activity from high (whole-body cooling)
      to low sympathetic activity (whole-body warming). Venous noradrenalin levels were
      determined bilaterally in five CRPS patients. (i) Three distinct vascular
      regulation patterns were identified related to the duration of the disorder. In
      the "warm" (acute) type of regulation, the affected limb was warmer and perfusion
      values were higher than in the contralateral limb during the entire spectrum of
      sympathetic activity. In the "intermediate" type of regulation the limb was
      either warmer or colder. In the "cold" (chronic) type of regulation, skin
      temperature and perfusion values were lower on the affected side during the
      entire spectrum of sympathetic vasoconstrictor activity. (ii) Noradrenalin levels
      were lower on the affected side, even in chronic patients with considerable
      cutaneous vasoconstriction. (iii) Temperature and blood flow differences between
      the two sides were dynamic and most prominent at a high to medium level of
      vasoconstrictor activity. (iv) In both control groups, there were only minor side
      differences in flow and temperature. In conclusion, it is suggested that, in CRPS
      I, unilateral inhibition of sympathetic vasoconstrictor neurones leads to a
      warmer affected limb in the acute stage. Secondary changes in neurovascular
      transmission may lead to vasoconstriction and cold skin in chronic CRPS I,
      whereas sympathetic activity is still depressed. Vascular abnormalities are
      dynamic. The maximal skin temperature difference that occurs during the
      thermoregulatory cycle distinguishes CRPS I from other extremity pain syndromes
      with high sensitivity and specificity.

PMID- 11222459
TI  - "Theory of mind" impairments and their relationship to executive functioning
      following frontal lobe excisions.
AB  - It has been suggested that mental states play an important role in determining
      behaviour and that mental state attributions ("theory of mind") underlie the
      ability to understand and predict other peoples' behaviour. Theory of mind was
      investigated in 31 patients with unilateral frontal lobe lesions (15 right-sided
      and 16 left-sided) by comparing their performance with that of 31 matched control
      subjects. The ability to infer first- and second-order beliefs was tested by
      requiring subjects to listen to stories in which a protagonist acted upon a false
      belief. Both patient groups exhibited significantly impaired performance on the
      two theory of mind measures. Both frontal lobe groups also exhibited a range of
      deficits in tests of executive functions, but analyses revealed that these seemed
      to be independent of theory of mind impairments. These findings are discussed in
      terms of the hypothesis of a specialized, adaptive brain system underlying theory
      of mind reasoning ability, and are related to observed difficulties in social
      functioning among patients with frontal lobe damage.

PMID- 11222460
TI  - Diffusion tensor imaging in patients with epilepsy and malformations of cortical
      development.
AB  - Malformations of cortical development (MCD) are a common cause of epilepsy.
      Studies of structural MRIs and PET data in patients with MCD have found
      widespread changes outside the visually identified lesions. The aim of this study
      was to investigate diffusion changes interictally in patients with MCD and to
      test the hypothesis that MCD would be associated with widespread abnormalities of
      diffusion. We used diffusion tensor imaging (DTI) and statistical parametric
      mapping (SPM) to compare objectively tissue organization in 22 patients with
      partial seizures and MCD, with 30 control subjects. Whole-brain DTI was acquired
      using echo planar imaging. Rotationally invariant anisotropy and diffusivity maps
      were calculated and, after normalization to Talairach space, each patient was
      compared with the group of control subjects using SPM. Areas of reduced
      anisotropy were found in 17 patients and areas of increased diffusivity in 10.
      Two patients had areas of increased anisotropy. There were no patients with
      reduced diffusivity. Areas of increased diffusivity were in general more
      extensive than areas of reduced anisotropy. Changes in tissue beyond the MCD,
      that appeared normal on conventional MRI, were found in six patients for
      anisotropy and nine patients for diffusivity. Both measurements showed widespread
      changes in tissue beyond the MCD, i.e. adding information to conventional MRI.
      Increased or abnormally located grey matter or pathological white matter with
      abnormal myelination or ectopic neurones could cause reduced anisotropy.
      Increased diffusivity could be caused by a defect of neurogenesis or cell loss
      resulting in increased extracellular space. The widespread nature of
      abnormalities should be considered if surgical treatment is contemplated.

PMID- 11222461
TI  - Diffusion tensor imaging of cryptogenic and acquired partial epilepsies.
AB  - Current optimal MRI identifies a relevant structural abnormality in up to 80% of
      patients with refractory partial seizures. Identification of a structural lesion
      is fundamental to pre-surgical evaluation. We used diffusion tensor imaging (DTI)
      and statistical parametric mapping (SPM) to examine objectively the diffusion
      properties, and hence structural organization, of cerebral tissue in 10 patients
      with partial seizures and acquired lesions and 30 patients with partial seizures
      and normal MRI. Fractional anisotropy and mean diffusivity maps were calculated
      and, using SPM, individual patients were compared with a group of 30 control
      subjects. Diffusion tensor imaging and voxel-by-voxel statistical comparisons
      identified significant increases in diffusivity and significant reductions of
      anisotropy in all patients with acquired non-progressive cerebral lesions and
      partial seizures. In all of these patients, the areas of increased diffusivity,
      and in nine patients the areas of decreased anisotropy, concurred with
      abnormalities identified on visual inspection of conventional MRI. In addition,
      there were 10 areas which were normal on conventional imaging which exhibited
      abnormal anisotropy or diffusivity. Individual analyses of the 30 patients with
      partial seizures and normal optimal MRI identified a significant increase in
      diffusivity in eight of the subjects. In six of these, the areas of increased
      diffusivity concurred with the localization of epileptiform EEG abnormality.
      Analysis of anisotropy in the MRI-negative patients revealed significant
      differences in two patients, one of which concurred with electroclinical seizure
      localization. Group analysis of nine patients with normal conventional MRI and
      electroclinical seizure onset localizing to the left temporal region revealed a
      significant increase in diffusivity and a significant reduction in anisotropy
      within the white matter of the left temporal lobe. DTI analysed using SPM was
      sensitive in patients with acquired cerebral damage. Significant differences in
      the diffusion indices in individual MRI negative patients and the group effect in
      patients with left temporal lobe epilepsy suggest that minor structural
      disorganization exists in occult epileptogenic cerebral lesions. These techniques
      are promising, non-invasive imaging methods for identifying the cause of partial
      seizures, and can contribute to pre-surgical evaluation.

PMID- 11222462
TI  - Adrenergic receptor polymorphisms and cardiac function (and dysfunction): a
      failure to communicate?

PMID- 11222463
TI  - Results of targeted anti-tumor necrosis factor therapy with etanercept (ENBREL)
      in patients with advanced heart failure.
AB  - BACKGROUND: Previously, we showed that tumor necrosis factor (TNF) antagonism
      with etanercept, a soluble TNF receptor, was well tolerated and that it
      suppressed circulating levels of biologically active TNF for 14 days in patients
      with moderate heart failure. However, the effects of sustained TNF antagonism in
      heart failure are not known. METHODS AND RESULTS: We conducted a randomized,
      double-blind, placebo-controlled, multidose trial of etanercept in 47 patients
      with NYHA class III to IV heart failure. Patients were treated with biweekly
      subcutaneous injections of etanercept 5 mg/m(2) (n=16) or 12 mg/m(2) (n=15) or
      with placebo (n=16) for 3 months. Doses of 5 and 12 mg/m(2) etanercept were safe
      and well tolerated for 3 months. Treatment with etanercept led to a significant
      dose-dependent improvement in left ventricular (LV) ejection fraction and LV
      remodeling, and there was a trend toward an improvement in patient functional
      status, as determined by clinical composite score. CONCLUSION: Treatment with
      etanercept for 3 months was safe and well-tolerated in patients with advanced
      heart failure, and it resulted in a significant dose-dependent improvement in LV
      structure and function and a trend toward improvement in patient functional
      status.

PMID- 11222464
TI  - Blunted cardiac responses to receptor activation in subjects with Thr164Ile
      beta(2)-adrenoceptors.
AB  - BACKGROUND: Recent evidence indicates that certain genotypes of beta(2)
      adrenoceptors (AR) may indicate an increased risk of cardiovascular disease or an
      increased rate of disease progression. Of particular importance, the Thr164Ile
      polymorphism, which is found in approximately 4% of humans, shows decreased
      receptor signaling, blunted cardiac response when expressed in transgenic mice,
      and is associated with a decreased survival rate in patients with congestive
      heart failure. METHODS AND RESULTS: In this study, we compared functional
      activity, ie, chronotropic (heart rate increases) and inotropic (duration of the
      electromechanical systole) responses to intravenously administered terbutaline,
      in 6 subjects (4 women and 2 men) who were heterozygous for Thr164Ile with the
      responses in 12 volunteers (6 women and 6 men) who were homozygous for wild-type
      (WT) beta(2)-AR (ie, Arg16, Gln27, and Thr164). The beta(2)AR polymorphism
      significantly affected the dose-response curves for terbutaline-induced inotropic
      and chronotropic responses: compared with WT individuals, subjects with the
      Thr164Ile receptor had substantial blunting in maximal increases in heart rate
      (WT, 29.7+/-3.9 beats/min; Ile164, 20.7+/-1.9 beats/min; P:=0.016) and a
      shortening of the duration of electromechanical systole (WT, 51.9+/-4.5 ms;
      Ile164, 37.9+/-4.6 ms; P:=0.02). CONCLUSIONS: These data show that humans with
      the Ile164 genotype show blunted cardiac beta(2)-AR responsiveness, which may
      help explain the decreased survival of patients with this genotype in the setting
      of congestive heart failure.

PMID- 11222465
TI  - The impact of calcification on the biomechanical stability of atherosclerotic
      plaques.
AB  - BACKGROUND: Increased biomechanical stresses in the fibrous cap of
      atherosclerotic plaques contribute to plaque rupture and, consequently, to
      thrombosis and myocardial infarction. Thin fibrous caps and large lipid pools are
      important determinants of increased plaque stresses. Although coronary
      calcification is associated with worse cardiovascular prognosis, the relationship
      between atheroma calcification and stresses is incompletely described. METHODS
      AND RESULTS: To test the hypothesis that calcification impacts biomechanical
      stresses in human atherosclerotic lesions, we studied 20 human coronary lesions
      with techniques that have previously been shown to predict plaque rupture
      locations accurately. Ten ruptured and 10 stable lesions derived from post mortem
      coronary arteries were studied using large-strain finite element analysis.
      Maximum stress was not correlated with percentage of calcification, but it was
      positively correlated with the percentage of lipid (P:=0.024). When calcification
      was eliminated and replaced with fibrous plaque, stress changed insignificantly;
      the median increase in stress for all specimens was 0.1% (range, 0% to 8%;
      P:=0.85). In contrast, stress decreased by a median of 26% (range, 1% to 78%;
      P:=0.02) when lipid was replaced with fibrous plaque. CONCLUSIONS: Calcification
      does not increase fibrous cap stress in typical ruptured or stable human coronary
      atherosclerotic lesions. In contrast to lipid pools, which dramatically increase
      stresses, calcification does not seem to decrease the mechanical stability of the
      coronary atheroma.

PMID- 11222466
TI  - Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and
      class A scavenger receptor expression in human monocyte-derived macrophages.
AB  - BACKGROUND: Excessive lipid accumulation in macrophages plays an important role
      in the development of atherosclerosis. Recently, we discovered an adipocyte
      specific plasma protein, adiponectin, that is decreased in patients with coronary
      artery disease. We previously demonstrated that adiponectin acts as a modulator
      for proinflammatory stimuli and inhibits monocyte adhesion to endothelial cells.
      The present study investigated the effects of adiponectin on lipid accumulation
      in human monocyte-derived macrophages. METHODS AND RESULTS: Human monocytes were
      differentiated into macrophages by incubation in human type AB serum for 7 days,
      and the effects of adiponectin were investigated at different time intervals.
      Treatment with physiological concentrations of adiponectin reduced intracellular
      cholesteryl ester content, as determined using the enzymatic, fluorometric
      method. The adiponectin-treated macrophages contained fewer lipid droplets
      stained by oil red O. Adiponectin suppressed the expression of the class A
      macrophage scavenger receptor (MSR) at both mRNA and protein levels by Northern
      and immunoblot analyses, respectively, without affecting the expression of CD36,
      which was quantified by flow cytometry. Adiponectin reduced the class A MSR
      promoter activity, as measured by luciferase reporter assay. Adiponectin
      treatment dose-dependently decreased class A MSR ligand binding and uptake
      activities. The mRNA level of lipoprotein lipase as a marker of macrophage
      differentiation was decreased by adiponectin treatment, but that of
      apolipoprotein E was not altered. Adiponectin was detected around macrophages in
      the human injured aorta by immunohistochemistry. CONCLUSIONS: The adipocyte
      derived plasma protein adiponectin suppressed macrophage-to-foam cell
      transformation, suggesting that adiponectin may act as a modulator for macrophage
      to-foam cell transformation.

PMID- 11222467
TI  - Chronic infections and the risk of carotid atherosclerosis: prospective results
      from a large population study.
AB  - BACKGROUND: Chronic infections have been implicated in the pathogenesis of
      atherosclerosis, yet from an epidemiological perspective, this concept remains
      controversial. METHODS AND RESULTS: The Bruneck Study is a prospective population
      based survey on the pathogenesis of atherosclerosis. In 826 men and women 40 to
      79 years old (1990 baseline), 5-year changes in carotid atherosclerosis were
      thoroughly assessed by high-resolution duplex scanning. The presence of chronic
      respiratory, urinary tract, dental, and other infections was ascertained by
      standard diagnostic criteria. Chronic infections amplified the risk of
      atherosclerosis development in the carotid arteries. The association was most
      pronounced in subjects free of carotid atherosclerosis at baseline (age-/sex
      adjusted odds ratio [95% CI] for any chronic infection versus none, 4.08 [2.42 to
      6.85]; P:<0.0001) and applied to all types of chronic (bacterial) infections. It
      remained independently significant after adjustment for classic vascular risk
      attributes and extended to low-risk individuals free of conventional risk
      factors. Among subjects with chronic infections, atherosclerosis risk was highest
      in those with a prominent inflammatory response. Markers of systemic
      inflammation, such as soluble adhesion molecules and circulating bacterial
      endotoxin, and levels of soluble human heat-shock protein 60 and antibodies to
      mycobacterial heat-shock protein 65 were elevated in subjects with chronic
      infections and predictive of an increased risk of atherosclerosis. CONCLUSIONS:
      The present study provides solid evidence for a role of common chronic infections
      in human atherogenesis. Induction of systemic inflammation and autoimmunity may
      be potential pathophysiological links.

PMID- 11222468
TI  - Antibodies to human heat-shock protein 60 are associated with the presence and
      severity of coronary artery disease: evidence for an autoimmune component of
      atherogenesis.
AB  - BACKGROUND: Antibodies to mycobacterial heat-shock protein (HSP) 65 have been
      reported to be associated with carotid artery thickening. We examined whether
      antibodies to human HSP60 are associated with the risk of coronary artery disease
      (CAD). METHODS AND RESULTS: Blood samples from 391 patients (62% men, mean age 57
      years) being evaluated for CAD by coronary angiography were tested for IgG
      antibodies to human HSP60 by ELISA. We found that 75% of the study subjects had
      anti-HSP60 antibodies. The prevalence of CAD was increased in seropositive
      compared with seronegative patients (68% versus 49%, P:=0.0009). Mean titers of
      HSP60 antibodies were higher in CAD patients than in non-CAD patients (P:=0.008).
      No association between HSP60 antibodies and infection or inflammation was found.
      Importantly, HSP60 antibodies were related to disease severity. The prevalence of
      HSP60 antibodies was 76%, 80%, and 85% in patients with 1-, 2-, and 3-vessel
      disease, compared with 64% in patients without CAD (P: for trend=0.003). A
      similar association between increasing antibody titers and number of diseased
      vessels was also found (P:=0.03). Significant associations between antibodies to
      HSP60 and CAD severity persisted after adjustment for traditional risk factors by
      age, race, sex, smoking, diabetes, hypercholesterolemia, hypertension, and C
      reactive protein levels. Adjusted OR for number of vessels diseased was 1.86 (95%
      CI 1.13 to 3.04). CONCLUSIONS: This is the first study demonstrating a
      significant association between human HSP60 antibodies and both the presence and
      severity of CAD.

PMID- 11222469
TI  - Similarity of ventricular function in patients alive 5 years after randomization
      to surgery or angioplasty in the BARI trial.
AB  - BACKGROUND: Left ventricular ejection fraction (LVEF) is a recognized determinant
      of survival in patients with coronary artery disease. In major trials comparing
      surgical and percutaneous revascularization approaches, the long-term effect of
      the coronary revascularization strategy on LVEF has not been reported. METHODS
      AND RESULTS: In the NHLBI-sponsored Bypass and Angioplasty Revascularization
      Investigation (BARI) randomized trial comparing angioplasty and bypass surgery as
      initial treatment strategies, 1220 (75%) of the 1617 surviving randomized
      patients had their EF measured by radionuclide ventriculography 5 years after
      study entry. For the total study group, the 5-year EF in the CABG group (n=623)
      was 55.8+/-12.3, compared with 55.7+/-12.7 in PTCA group (n=597, P:=0.82). There
      was no significant difference in measured EF between the CABG group and the PTCA
      group within multiple subgroups determined by the presence or absence of
      diabetes, 3-vessel disease, complete revascularization, or prior myocardial
      infarction. In a multiple linear regression model developed to predict 5-year EF,
      treatment assignment to PTCA or CABG was not significant (P:=0.95). If an EF of 0
      was imputed for patients who were dead and missing EF data, however, there was a
      higher EF in the CABG group (P:=0.0018) among diabetic patients only.
      CONCLUSIONS: In the BARI randomized trial, initial treatment assignment to
      angioplasty was not associated with any difference in long-term ventricular
      function compared with initial treatment assignment to surgery. These results
      apply, however, only to patients who were alive at 5 years.

PMID- 11222470
TI  - Beneficial effects of pentoxifylline in patients with idiopathic dilated
      cardiomyopathy treated with angiotensin-converting enzyme inhibitors and
      carvedilol: results of a randomized study.
AB  - BACKGROUND: We previously reported beneficial effects of pentoxifylline, a
      xanthine-derived agent known to inhibit the production of tumor necrosis factor
      alpha, in patients with idiopathic dilated cardiomyopathy treated with diuretics,
      digoxin, and ACE inhibitors. Since then, 3 large clinical trials showed important
      clinical benefits of beta-blockers in this population. Therefore, we designed the
      present study to establish whether in patients with heart failure already
      receiving treatment with ACE inhibitors and beta-blockers, the addition of
      pentoxifylline would have an additive beneficial effect. METHODS AND RESULTS: In
      a single-center, prospective, double-blind, randomized, placebo-controlled study,
      39 patients with idiopathic dilated cardiomyopathy were randomized to
      pentoxifylline 400 mg TID (n=20) or placebo (n=19) if they had a left ventricular
      ejection fraction <40% after 3 months of therapy with digoxin, ACE inhibitors,
      and carvedilol. Primary end points were New York Heart Association functional
      class, exercise tolerance, and left ventricular function. Patients were followed
      up for 6 months. Five patients died (3 in the placebo group). Patients treated
      with pentoxifylline had a significant improvement in functional class compared
      with the placebo group (P:=0.01), with an increment in exercise time from 9.5+/-5
      to 12.3+/-6 minutes (P:=0.1). Left ventricular ejection fraction improved from
      24+/-9% to 31+/-13%, P:=0.03, in the treatment group. CONCLUSIONS: In patients
      with idiopathic dilated cardiomyopathy, the addition of pentoxifylline to
      treatment with digoxin, ACE inhibitors, and carvedilol is associated with a
      significant improvement in symptoms and left ventricular function.

PMID- 11222471
TI  - Signaling pathways responsible for fetal gene induction in the failing human
      heart: evidence for altered thyroid hormone receptor gene expression.
AB  - BACKGROUND: We have previously demonstrated that changes in myosin heavy chain
      (MHC) isoforms that occur in failing human hearts resemble the pattern produced
      in rodent myocardium in response to hypothyroidism. Because thyroid hormone
      status is usually within normal limits in these patients, we hypothesized that
      failing/hypertrophied human myocardium might have a defect in thyroid hormone
      signaling due to alterations in expression of thyroid hormone receptors (TRs).
      METHODS AND RESULTS: To examine this hypothesis, we used RNase protection assay
      to measure mRNA levels of TRs in failing left ventricles that exhibited a fetal
      pattern of gene expression, ie, decreased expression of alpha-MHC with increased
      beta-MHC expression compared with left ventricles from age-matched controls. We
      detected expression of TR-alpha(1), -alpha(2), and -beta(1) isoforms in human
      left ventricles. In failing left ventricles, TR-alpha(1) was downregulated,
      whereas TR-alpha(2), a splice variant that does not bind thyroid hormone but
      inhibits responses to liganded TRs, was increased. Expression levels of TR
      beta(1) did not differ significantly between the 2 groups. According to linear
      regression analysis, expression levels of TR-alpha(1) and -alpha(2) were
      positively and negatively correlated with those of alpha-MHC, respectively.
      CONCLUSIONS: We conclude that decreases in TR-alpha(1) and increases in TR
      alpha(2) may lead to local attenuation of thyroid hormone signaling in the
      failing human heart and that the resulting tissue-specific hypothyroidism is a
      candidate for the molecular mechanism that induces fetal gene expression in the
      failing human ventricle.

PMID- 11222472
TI  - Notched T waves on Holter recordings enhance detection of patients with LQt2
      (HERG) mutations.
AB  - BACKGROUND: The 2 genes KCNQ1 (LQT1) and HERG (LQT2), encoding cardiac potassium
      channels, are the most common cause of the dominant long-QT syndrome (LQTS). In
      addition to QT-interval prolongation, notched T waves have been proposed as a
      phenotypic marker of LQTS patients. METHODS AND RESULTS: The T-wave morphology of
      carriers of mutations in KCNQ1 (n=133) or HERG (n=57) and of 100 control subjects
      was analyzed from Holter ECG recordings. Averaged T-wave templates were obtained
      at different cycle lengths, and potential notched T waves were classified as
      grade 1 (G1) in case of a bulge at or below the horizontal, whatever the
      amplitude, and as grade 2 (G2) in case of a protuberance above the horizontal.
      The highest grade obtained from a template defined the notch category of the
      subject. T-wave morphology was normal in the majority of LQT1 and control
      subjects compared with LQT2 (92%, 96%, and 19%, respectively, P:<0.001). G1
      notches were relatively more frequent in LQT2 (18% versus 8% [LQT1] and 4%
      [control], P:<0.01), and G2 notches were seen exclusively in LQT2 (63%).
      Predictors for G2 were young age, missense mutations, and core domain mutations
      in HERG. CONCLUSIONS: This study provides novel evidence that Holter recording
      analysis is superior to the 12-lead ECG in detecting G1 and G2 T-wave notches.
      These repolarization abnormalities are more indicative of LQT2 versus LQT1, with
      G2 notches being most specific and often reflecting HERG core domain missense
      mutations.

PMID- 11222473
TI  - Bundle-branch reentry and the postpacing interval after entrainment by right
      ventricular apex stimulation: a new approach to elucidate the mechanism of wide
      QRS-complex tachycardia with atrioventricular dissociation.
AB  - BACKGROUND: Diagnosis of bundle-branch reentry ventricular tachycardia (BBR-VT)
      by the standard approach is challenging, and this may lead to nonrecognition of
      this tachycardia mechanism. Because the postpacing interval (PPI) after
      entrainment has been correlated with the distance from the pacing site to the
      reentrant circuit, BBR-VT entrainment by pacing from the right ventricular apex
      (RVA) should result in a PPI similar to the tachycardia cycle length (TCL). This
      factor may differentiate BBR-VT from other mechanisms of wide-QRS-complex
      tachycardia with AV dissociation, such as myocardial reentrant VT (MR-VT) or AV
      nodal reentrant tachycardia (AVNRT), in which the circuit is usually located away
      from the RVA. METHODS AND RESULTS: Transient entrainment by RVA pacing was
      attempted in 18 consecutive BBR-VTs and finally achieved in 13. Results were
      compared with those found in 59 consecutive MR-VTs and 50 consecutive AVNRTs. The
      mean PPI-TCL difference was significantly (P:<0.0001) shorter in the BBR-VT group
      (9+/-11 ms) than in the MR-VT (109+/-48 ms) and the AVNRT (150+/-29 ms) groups.
      No BBR-VT showed a PPI-TCL >30 ms (range -12 to 24 ms). Except for 2 MR-VTs, no
      MR-VT (range 21 to 211 ms) or AVNRT (range 100 to 215 ms) showed a PPI-TCL <30
      ms. CONCLUSIONS: A PPI-TCL >30 ms, after entrainment by RVA stimulation, makes
      BBR-VT unlikely. Conversely, a PPI-TCL <30 ms is suggestive of BBR-VT but should
      lead to further investigation by use of conventional criteria.

PMID- 11222474
TI  - Peripheral flow response to transient arterial forearm occlusion does not reflect
      myocardial perfusion reserve.
AB  - BACKGROUND: Ultrasonographic evaluation of systemic arterial function is widely
      available, and a close relation of endothelial function in the coronary and
      brachial arteries has been documented. It is unknown, however, whether a similar
      correlation exists for their 2 microcirculatory territories and thus whether
      assessment of the systemic microcirculation can be used similarly as a surrogate
      marker of myocardial perfusion. METHODS AND RESULTS: Twenty-three patients with
      documented coronary artery disease (CAD; 66+/-9 years old, 18 men), 16 patients
      with syndrome X (SX; 56+/-5 years old, 13 women), and 45 healthy control subjects
      (C; 34+/-9 years old, 22 men) were studied. Myocardial perfusion was measured at
      rest and after dipyridamole (0.56 mg. kg(-1). min(-1) over 4 minutes) by PET, and
      brachial artery blood flow was measured at rest and after transient forearm
      ischemia by standard Doppler ultrasound techniques. Dipyridamole increased
      myocardial perfusion in all groups (mL. g(-1). min(-1): CAD, 0.89+/-0.27 versus
      1.62+/-0.67, P:<0.001; SX, 0.82+/-0.16 versus 1.67+/-0.49, P:<0.001; and C,
      0.82+/-0.15 versus 2.32+/-0.64, P:<0.001). Postocclusion forearm flow increased
      similarly in all groups (CAD, 52+/-18 versus 174+/-77 mL/min, P:<0.001; SX, 49+/
      29 versus 202+/-82 mL/min, P:<0.001; and C, 61+/-34 versus 229+/-108 mL/min,
      P:<0.001). No significant correlations were found between peripheral and
      myocardial microcirculatory beds for either resting flow, hyperemic flow, or flow
      reserve in any of the groups (r(2)<0.1, P:=NS). CONCLUSIONS: The peripheral
      perfusion responses to transient forearm ischemia do not correlate with
      dipyridamole-induced myocardial hyperemia. The lack of correlation indicates
      different mechanisms of microvascular activation or regulation and confirms that
      extrapolations between findings in the 2 vascular beds are not suitable.

PMID- 11222475
TI  - Inducible nitric oxide synthase deficiency does not affect the susceptibility of
      mice to atherosclerosis but increases collagen content in lesions.
AB  - BACKGROUND: Although endothelial nitric oxide synthase (NOS) is antiatherogenic,
      the role of inducible NOS (iNOS) in the development of atherosclerosis is not
      established. METHODS AND RESULTS: We compared the susceptibility of iNOS knockout
      (iNOS(-/-)) and wild-type (iNOS(+/+)) mice to the development of atherosclerosis
      induced by feeding an atherogenic diet for 15 weeks. Plasma lipid level,
      atherosclerotic lesion size, and cellular density in the lesions were all similar
      in the 2 strains (lesion size: iNOS(+/+) 285+/-73x10(3) microm(2), iNOS(-/-)
      293+/-82x10(3) microm(2), n=10). iNOS mRNA was detected in the lesions of
      iNOS(+/+) but not iNOS(-/-) mice through RT-PCR. Immunohistochemically, iNOS(+/+)
      mice showed iNOS staining in macrophages and medial smooth muscle cells in the
      lesions. Nitrotyrosine staining showed a similar distribution, whereas it was
      absent in iNOS(-/-) mice. There was no apparent difference in the intensity or
      distribution of vascular cell adhesion molecule-1 staining in the lesions of the
      2 strains. However, the lesions of iNOS(+/+) mice showed a markedly decreased
      extracellular collagen content compared with those of iNOS(-/-) mice CONCLUSIONS:
      iNOS induction does not affect the development of atherosclerosis in mice fed an
      atherogenic diet, but the resulting lesions show decreased levels of
      extracellular collagen and may be more fragile.

PMID- 11222476
TI  - Transforming growth factor-beta(1) stimulates L-arginine transport and metabolism
      in vascular smooth muscle cells: role in polyamine and collagen synthesis.
AB  - BACKGROUND: Transforming growth factor-beta(1) (TGF-beta(1)) contributes to
      arterial remodeling by stimulating vascular smooth muscle cell (VSMC) growth and
      collagen synthesis at sites of vascular injury. Because L-arginine is metabolized
      to growth-stimulatory polyamines and to the essential collagen precursor L
      proline, we examined whether TGF-beta(1) regulates the transcellular transport
      and metabolism of L-arginine by VSMCs. METHODS AND RESULTS: TGF-beta(1) increased
      L-arginine uptake, and this was associated with a selective increase in cationic
      amino acid transporter-1 (CAT-1) mRNA. In addition, TGF-beta(1) stimulated L
      arginine metabolism by inducing arginase I mRNA and arginase activity. TGF
      beta(1) also stimulated L-ornithine catabolism by elevating ornithine
      decarboxylase (ODC) and ornithine aminotransferase (OAT) activity. TGF-beta(1)
      markedly increased the capacity of VSMCs to generate the polyamine putrescine and
      L-proline from extracellular L-arginine. The TGF-beta(1)-mediated increase in
      putrescine and L-proline production was reversed by methyl-L-arginine, a
      competitive inhibitor of cationic amino acid transport, or by hydroxy-L-arginine,
      an arginase inhibitor. Furthermore, the formation of putrescine was inhibited by
      the ODC inhibitor alpha-difluoromethylornithine, and L-proline generation was
      blocked by the OAT inhibitor L-canaline. L-Canaline also inhibited TGF-beta(1)
      stimulated type I collagen synthesis. CONCLUSIONS: These results demonstrate that
      TGF-beta(1) stimulates polyamine and L-proline synthesis by inducing the genes
      that regulate the transport and metabolism of L-arginine. In addition, they show
      that TGF-beta(1)-stimulated collagen production is dependent on L-proline
      formation. The ability of TGF-beta(1) to upregulate L-arginine transport and
      direct its metabolism to polyamines and L-proline may contribute to arterial
      remodeling at sites of vascular damage.

PMID- 11222477
TI  - Recombinant soluble p-selectin glycoprotein ligand-1-Ig reduces restenosis
      through inhibition of platelet-neutrophil adhesion after double angioplasty in
      swine.
AB  - BACKGROUND: P-selectin mediates leukocyte recruitment to activated platelets and
      endothelium through its high-affinity receptor P-selectin glycoprotein ligand-1
      (PSGL-1). Platelet and leukocyte activation and binding have been reported after
      coronary angioplasty and were correlated with restenosis. We investigated the
      effect of a recombinant soluble PSGL-1 (rPSGL-Ig) on the adhesion of platelets
      and neutrophils and the development of restenosis after double arterial injury.
      METHODS AND RESULTS: Four weeks after angioplasty of both carotid arteries in
      pigs, a second angioplasty was performed at the same sites, 15 minutes after a
      single administration of vehicle or rPSGL-1 (1 mg/kg IV). Animals were euthanized
      1 hour, 4 hours, 1 week, or 4 weeks later. Adhesion of autologous (51)Cr
      platelets and (111)In-neutrophils was quantified and histological/morphometric
      analyses were performed. Although rPSGL-Ig did not affect adherence of these
      cells 1 hour after injury, it significantly reduced the adhesion of platelets
      (50% at 4 hours and 85% at 1 week) and neutrophils (50% at 4 hours and 78% at 1
      week) to deeply injured arteries. At 4 weeks, the residual lumen was 63% larger
      in rPSGL-Ig-treated arteries as compared with control arteries (6.1+/-0.6 versus
      3.8+/-0.1 mm(2); P:<0.002). The neointimal area was slightly reduced (0.5 in
      rPSGL-Ig versus 0.7 mm(2) in control). The ratio of the external elastic lamina
      of injured to uninjured reference segments was >1 in treated arteries and <1 in
      control arteries. CONCLUSIONS: P-selectin antagonism with rPSGL-Ig inhibits early
      platelet/leukocyte adhesion on injured arteries and reduces restenosis through a
      positive impact on vascular remodeling. Hence, rPSGL-Ig may have potential in the
      prevention of restenosis.

PMID- 11222478
TI  - Effect of selective or combined inhibition of integrins alpha(IIb)beta(3) and
      alpha(v)beta(3) on thrombosis and neointima after oversized porcine coronary
      angioplasty.
AB  - BACKGROUND: Thrombosis and neointima formation limit the efficacy of coronary
      angioplasty (PTCA). Clinical trials have implicated the adhesion molecules
      integrin alpha(IIb)beta(3) and integrin alpha(v)beta(3) in these processes. The
      roles of these molecules in vascular smooth muscle cell adhesion, platelet
      aggregation, and the thrombotic and neointimal response to oversize porcine PTCA
      was investigated by use of a selective alpha(IIb)beta(3) antagonist (lamifiban),
      a selective alpha(v)beta(3) antagonist (VO514), and a combined
      alpha(IIb)beta(3)/alpha(v)beta(3) antagonist (G3580). METHODS AND RESULTS: In
      vitro, both alpha(v)beta(3) inhibitors caused dose-dependent inhibition of
      porcine vascular smooth muscle cell adhesion to vitronectin but not to collagen
      type IV, fibronectin, or laminin, whereas selective alpha(IIb)beta(3) inhibition
      had no effect. Intravenous infusions of either alpha(IIb)beta(3) inhibitor in
      swine profoundly inhibited ex vivo platelet aggregation to ADP, whereas selective
      alpha(v)beta(3) inhibition had no effect. In a porcine PTCA model, intravenous
      infusions of the integrin antagonists were administered for 14 days after
      oversized balloon angioplasty injury. After PTCA, there was regional upregulation
      of integrin alpha(v)beta(3) in the developing neointima, as assessed by
      immunohistochemistry. Six hours after PTCA, obstruction of lumen by thrombus was
      reduced significantly by alpha(IIb)beta(3) inhibition compared with either
      control or alpha(v)beta(3) inhibition (mean control, 18.7%; VO514, 18.5%;
      lamifiban, 6.4%; G3580, 7.9%). Twenty-eight days after PTCA, there was a
      significant reduction of neointima with inhibitors of either integrin (mean
      intima/media ratio: control, 3.08; VO514, 1.33; lamifiban, 0.97; G3580, 1.32).
      CONCLUSIONS: We conclude that both integrin alpha(IIb)beta(3) and integrin
      alpha(v)beta(3) participate in neointima development after experimental
      angioplasty.

PMID- 11222480
TI  - Mechanisms of resetting reentrant circuits in canine ventricular tachycardia.
AB  - BACKGROUND: Resetting has been used to characterize reentrant circuits causing
      clinical tachycardias. METHODS AND RESULTS: To determine the mechanisms of
      resetting, sustained ventricular tachycardia was induced in dogs with 4-day-old
      myocardial infarctions by programmed stimulation. Premature stimulation was
      accomplished from multiple regions within reentrant circuits; resetting curves
      were constructed and compared with activation maps. Monotonically increasing
      responses, or a "mixed" response (increasing portion preceded by a flat portion),
      occurred. All reentrant circuits had a fully excitable gap. Interval-dependent
      conduction delay and concealed retrograde penetration led to increased resetting
      response curves. CONCLUSIONS: Multiple mechanisms revealed by mapping cause
      resetting of reentrant circuits.

PMID- 11222479
TI  - Evidence of macrophage foam cell formation by very low-density lipoprotein
      receptor: interferon-gamma inhibition of very low-density lipoprotein receptor
      expression and foam cell formation in macrophages.
AB  - BACKGROUND: Expression of the VLDL receptor, primarily in macrophages, has been
      confirmed in human and rabbit atherosclerotic lesions. The high binding affinity
      of the VLDL receptor for remnant particles implicates the VLDL receptor pathway
      in the foam cell formation mechanism in macrophages. This study investigates the
      effect of interferon (IFN)-gamma on VLDL receptor expression in phorbol-12
      myristate-13-acetate (PMA)-treated THP-1, HL-60 macrophages, and human monocyte
      derived macrophages. METHODS AND RESULTS: THP-1 cells were induced to
      differentiate into macrophages by PMA treatment. IFN-gamma was added to the
      medium, and expression of the VLDL receptor was determined. (125)I-beta-VLDL
      degradation study and oil red O staining were examined. In THP-1 macrophages,
      VLDL receptor protein expression decreased at 2 days after PMA treatment but
      increased at 3 days and increased up to 5 days. Scavenger receptor proteins,
      which were not originally present, appeared at 3 days after PMA treatment. IFN
      gamma inhibited VLDL receptor expression in a dose-and time-dependent manner in
      macrophages. However, no inhibitory effect was observed in monocytes. Moreover,
      IFN-gamma receptor mRNA increased during differentiation to macrophages. (125)I
      beta-VLDL degradation study and oil red O staining showed that IFN-gamma
      significantly inhibited foam cell formation after the uptake of beta-VLDL. LDL
      receptor-related protein (LRP) and LDL receptor mRNAs were not expressed in
      macrophages. In PMA-treated HL-60 macrophages and human monocyte-derived
      macrophages, IFN-gamma also inhibited VLDL receptor expression and foam cell
      formation by beta-VLDL. CONCLUSIONS: VLDL receptor expression is upregulated
      during monocyte-macrophage differentiation. IFN-gamma inhibits VLDL receptor
      expression and foam cell formation only in macrophages. Remnant particles induce
      macrophage foam cell formation through the VLDL receptor pathway.

PMID- 11222481
TI  - Pulmonary veins and ligament of Marshall as sources of rapid activations in a
      canine model of sustained atrial fibrillation.
AB  - BACKGROUND: In dogs, chronic rapid pacing may result in sustained atrial
      fibrillation (AF). However, activation patterns in pacing-induced sustained AF
      are unclear. METHODS AND RESULTS: We induced sustained AF (>48 hours) in 6 dogs
      by rapid pacing for 139+/-84 days. We then performed computerized atrial
      epicardial mappings and recorded the activations in the ligament of Marshall
      (LOM) and the pulmonary veins (PVs). During AF, mean activation cycle length in
      the right atrial free wall (126+/-17 ms) was significantly longer than that in
      the left atrial free wall (96+/-5 ms, P:=0.006). In addition, mean activation
      cycle length in the left atrial free wall was significantly longer than that in
      the LOM (84+/-5 ms, P:<0.001), the left inferior PV (81+/-4 ms, P:=0.001), and
      the left superior PV (85+/-7 ms, P:=0.003). Similarly, the dominant frequency was
      highest in the LOM and the PVs (range 11.2 to 13.3 Hz), followed by the left and
      right atria (P:<0.001). In all dogs studied, rapid and complicated electrograms
      were consistently observed at the LOM and the PVs. During AF, both wandering
      wavelets and organized reentry were present. There were more wave fronts in the
      left atrium than in the right atrium (P:<0.001). CONCLUSIONS: In chronic pacing
      induced sustained AF, the LOM and the PVs are the sources of rapid activations.
      The mechanism by which the left atrium activates faster and has more wave fronts
      than the right atrium may relate to the fact that the left atrium is closer to
      the sources of rapid activations.

PMID- 11222482
TI  - Induction of rapid atherogenesis by perivascular carotid collar placement in
      apolipoprotein E-deficient and low-density lipoprotein receptor-deficient mice.
AB  - BACKGROUND: Perivascular collar placement has been used as a means for localized
      atherosclerosis induction in a variety of experimental animal species. In mice,
      however, atherosclerosis-like lesions have thus far not been obtained by this
      method. The aim of this study was the development of a mouse model of rapid, site
      controlled atherogenesis. METHODS AND RESULTS: Silastic collars were placed
      around the carotid arteries of apolipoprotein E-deficient (apoE-/-) and LDL
      receptor-deficient (LDLr-/-) mice. The development of collar-induced lesions was
      found to occur predominantly in the area proximal to the collar and to be
      dependent on a high-cholesterol diet. Lesions were evident in apoE-/- mice after
      3 weeks and in LDLr-/- mice after 6 weeks and were overtly atherosclerotic in
      appearance. Lumen stenosis reached 85% in apoE-/- mice and 61% in LDLr-/- mice 6
      weeks after collar insertion. Expression levels of intercellular adhesion
      molecule-1 and vascular cell adhesion molecule-1 were increased both proximal and
      distal to the collar, whereas endothelial nitric oxide synthase expression was
      downregulated at the proximal site. CONCLUSIONS: We propose that this model of
      collar-induced acceleration of carotid atherogenesis is of hemodynamic cause. It
      may serve as a substrate for sequential mechanistic studies concerned with the
      underlying cause and pathogenesis of atherosclerosis. The rapidity of lesion
      development will also aid the efficient screening of new potentially
      antiatherogenic chemical entities and the evaluation of therapies with limited
      duration of effectiveness, such as adenoviral gene therapy.

PMID- 11222483
TI  - Bolus fibrinolysis: risk, benefit, and opportunities.

PMID- 11222484
TI  - Coronary dissection and occlusion due to sports injury.

PMID- 11222485
TI  - AHA Science Advisory. Stanol/sterol ester-containing foods and blood cholesterol
      levels. A statement for healthcare professionals from the Nutrition Committee of
      the Council on Nutrition, Physical Activity, and Metabolism of the American Heart
      Association.
AB  - Considerable attention in the recent past has focused on the potential benefits
      or adverse effects of butter versus different types of margarines, usually with
      respect to their relative content of polyunsaturated, saturated, and trans fatty
      acids, and the impact of these on low-density lipoprotein (LDL) cholesterol
      levels. Recently, a new class of margarines and other fat-derived products (eg,
      salad dressings, mayonnaise) containing plant-derived sterols that are intended
      for use to lower blood cholesterol levels have been introduced into the food
      supply. These products are being marketed as adjuncts to low-saturated-fat and
      low-cholesterol diets to maximize reductions in LDL cholesterol levels achievable
      by dietary means.

PMID- 11222487
TI  - Meeting highlights : highlights of the 22nd congress of the european society of
      cardiology.

PMID- 11222486
TI  - Development of unilateral pulmonary arteriovenous malformations due to unequal
      distribution of hepatic venous flow.

PMID- 11222488
TI  - Patent foramen ovale and stroke.

PMID- 11222489
TI  - History repeats itself.

PMID- 11222490
TI  - Monocyte tissue factor induction by C-reactive protein and relationship with
      hormone replacement treatment.

PMID- 11222491
TI  - Aggrenox and stress testing.

PMID- 11222492
TI  - Antioxidants and prevention of restenosis after directional coronary atherectomy.

PMID- 11222493
TI  - Cardiovascular news.

PMID- 11222494
TI  - Identification of genetic loci associated with paralysis, inflammation and weight
      loss in mouse experimental autoimmune encephalomyelitis.
AB  - Experimental autoimmune encephalomyelitis (EAE), a model for human multiple
      sclerosis, is an inducible inflammatory and demyelinating disease of the central
      nervous system (CNS). Susceptibility to this disease is heritable and is
      demonstrated by the development of an ascending paralysis accompanied by a loss
      in body wt 2-3 weeks following immunization with proteins derived from CNS
      myelin. In a previous genetic analysis of susceptibility to EAE in a cross
      between susceptible SJL/J mice and resistant B10.S mice, we found suggestive
      evidence of linkage with disease susceptibility at the telomeric end of
      chromosome 2 and in the central region of chromosome 3. To define these
      associations more precisely and to investigate the genetic factors controlling
      measurable phenotypes of EAE, we performed a new analysis with a larger number of
      mice. The results now indicate that the chromosome 2 locus significantly
      influences EAE-related weight loss (P = 6.7 x 10(-5)) and that the chromosome 3
      locus is linked with the development of paralysis. In addition, an intriguing
      inheritance pattern was revealed in which female backcross mice generated from
      B10.S female x (B10.S x SJL/J)F(1) male parents experienced significantly more
      EAE-related weight loss (P = 1.2 x 10(-4)) than females generated from F1 female
      x B10.S male parents. After controlling for this inheritance, a new locus at the
      centromeric end of chromosome 8 was identified that significantly influences both
      the development of paralysis (P = 8.2 x 10(-6)) and the incidence of CNS
      inflammation (P = 7.0 x 10(-5)) in EAE.

PMID- 11222495
TI  - Immunization with tumor-associated epitopes fused to an endoplasmic reticulum
      translocation signal sequence affords protection against tumors with down
      regulated expression of MHC and peptide transporters.
AB  - Treatment of human cancers with an inherent antigen-processing defect due to a
      loss of peptide transporters (TAP-1 and TAP-2) and/or MHC class I antigen
      expression remains a considerable challenge. There is now an increasing
      realization that tumor cells with down-regulated expression of TAP and/or MHC
      class I antigens display strong resistance to cytotoxic T lymphocyte (CTL)
      mediated immune control, and often fail to respond to the conventional
      immunotherapeutic protocols based on active immunization with tumor-associated
      epitopes (TAE) or adoptive transfer of tumor-specific T cells. In the present
      study, we describe a novel approach based on immunization with either genetically
      modified tumor cells or naked DNA vectors encoding TAE fused to an endoplasmic
      reticulum (ER) signal sequence (ER-TAE) which affords protection against
      challenge by melanoma cells with down-regulated expression of TAP-1/2 and MHC
      class I antigens. In contrast, animals immunized with a vaccine based on TAE
      alone showed no protection against tumor challenge. Although MHC-peptide tetramer
      analysis showed a similar frequency of antigen-specific CTL in both ER-TAE- and
      TAE-immunized mice, functional analysis revealed that CTL activated following
      immunization with ER-TAE displayed significantly higher avidity for TAE when
      compared to animals immunized with the TAE alone. These observations provide a
      new strategy in anti-cancer vaccine design that allows activation of a highly
      effective and well-defined CTL response against tumors with down-regulated
      expression of TAP and MHC class I antigens.

PMID- 11222496
TI  - CD40-mediated signaling in monocytic cells: up-regulation of tumor necrosis
      factor receptor-associated factor mRNAs and activation of mitogen-activated
      protein kinase signaling pathways.
AB  - The biochemical pathways involved in CD40 signaling have been extensively studied
      in B cells and B cell lines, and appear to be primarily initiated by recruitment
      of the tumor necrosis factor (TNF) receptor-associated factor (TRAF) signaling
      proteins to the CD40 cytoplasmic domain. Signaling pathways activated through
      CD40 in monocytes/macrophages have not been characterized as well as in B cells.
      Using human monocytes and the human monocytic cell line THP1, we examined signal
      transduction events induced by CD40 engagement with its ligand, CD154. In human
      monocytes, all TRAF mRNAs were expressed constitutively and CD40 ligation
      resulted in a strong up-regulation of TRAF1 mRNA. In THP1 cells, CD40 ligation
      induced expression of TRAF1 and TRAF5 mRNAs. Engagement of CD40 in both monocytes
      and THP1 cells led to the rapid and transient activation of the extracellular
      signal-regulated kinases (ERK) 1 and 2, and to low levels of JNK activation. No
      CD40-dependent activation of p38 mitogen-activated protein kinase (MAPK) was
      found. In CD154-stimulated monocytes and THP1 cells the upstream ERK1/2
      activator, MAPK kinase (MEK) 1/2, and downstream substrate, c-Myc, were
      activated. By blocking activation of ERK1/2 with a MEK-specific inhibitor,
      PD98059, CD40-dependent secretion of the pro-inflammatory cytokines, TNF-alpha,
      IL-6 and IL-8, was demonstrated to be linked to the ERK1/2 pathway. The ERK1/2
      pathway did not appear to be involved in up-regulating TRAF1 and TRAF5 mRNAs in
      THP1 cells. Collectively, these results suggest distinct differences between B
      cells and monocytic cells in CD40-dependent activation of MAPK pathways.

PMID- 11222497
TI  - Difference in apoptosis induction between surface IgD and IgM.
AB  - In the classic 'two-signal' model for B cell activation, signal 1 through the
      antigen receptor plus signal 2 through lymphokine receptors and CD40 leads to
      proliferation, but signal 1 alone leads to tolerance or anergy. In a protocol
      designed to deliver signal 1 in vitro with anti-delta without signal 2, purified
      small dense B cells from untreated mice exposed to any of three monoclonal anti
      delta antibodies or to polyclonal anti-delta in vitro showed modest S phase entry
      at 50 microg/ml. In contrast, at low doses (0.1-0.5 microg/ml) of anti-delta,
      there was no cell cycle entry at 64 h, but apoptosis was accelerated at 16 h.
      Polyclonal anti-mu and three monoclonal anti-mus did not show this early
      apoptosis induction. Anti-CD40 and IL-4 inhibited apoptosis in B cells treated
      with 0.5 microg/ml anti-delta and increased S phase entry at 10 microg/ml anti
      delta. Low-dose anti-delta (but not anti-mu) induced increased B7-2 and class II
      MHC expression on a subset of B cells, many of which were in apoptosis. Larger
      transient increases in c-Myc and Egr-1 expression were seen with low-dose anti
      delta than with anti-mu, followed by an abrupt fall below baseline, a sequence
      previously linked to apoptosis. There was no change in Bcl-2, Bcl-x(L) or Bax.
      These data suggest a functional difference between delta and mu cross-linking on
      resting spleen B cells. A BCR stimulus sufficient for early activation events,
      but insufficient for full G1 entry, may lead to apoptosis.

PMID- 11222498
TI  - IL-4 gene expression up-regulated by mercury in rat mast cells: a role of oxidant
      stress in IL-4 transcription.
AB  - In the Brown Norway (BN) rat, chemical compounds [mercuric chloride (HgCl2), D
      penicillamine or gold salts] induce a T(h)2-dominated autoimmune syndrome with
      tissue injury in the form of a vasculitis and arthritis. An early phase of
      vasculitis in the model occurs within 24 h of an injection of HgCl2, is alphabeta
      T cell independent and involves the mast cell. In addition, HgCl2 induces IL-4
      mRNA in mast cells from BN rats. Our recent work has demonstrated that the
      balance of oxidative/antioxidative influences plays an important role in the
      modulation of mast cell function (degranulation) in chemically induced
      autoimmunity. The aim of this study was to determine, in mast cells, whether
      oxidative status influences IL-4 transcription and translation, which is required
      for the development of a T(h)2 response. Exposure of the mast cell line RBL-2H3
      to HgCl2 enhanced both IL-4 mRNA and its promoter activity. Oxidative stress by
      hydrogen peroxide mimicked the effects of HgCl2 in enhancing IL-4 promoter
      activity. The enhancement of IL-4 gene expression by HgCl2 was significantly
      reduced by antioxidants (both sulphydryl and non-sulphydryl containing). The same
      pattern of regulation was also observed on IL-4 protein expression in the mast
      cells. These data suggest a novel mechanism of IL-4 transcriptional up-regulation
      by oxidative stress. Our results provide evidence to support our hypothesis that
      alterations in intracellular reactive oxygen species production modulate both IL
      4 gene expression and mast cell function.

PMID- 11222499
TI  - A potential role for protein tyrosine kinase p56(lck) in rheumatoid arthritis
      synovial fluid T lymphocyte hyporesponsiveness.
AB  - Rheumatoid arthritis (RA) synovial fluid (SF)-T lymphocytes appear relatively
      inactive in situ and respond only weakly to diverse stimuli ex vivo. To
      characterize the molecular defects underlying this hyporesponsiveness we analyzed
      the expression level of several proteins involved in TCR-proximal signal
      transduction. As compared to peripheral blood (PB)-T lymphocytes, SF-T cells from
      some (but not all) of the patients analyzed expressed lower levels of
      TCRalphabeta, CD3epsilon, TCRzeta, p56(lck) and LAT, while p59(fyn),
      phospholipase C-gamma1 and ZAP-70 expression was unaltered. Semi-quantitative
      analysis of T cells from several patients revealed that the degree of TCRzeta
      chain and p56(lck) modulation correlated statistically significantly with the
      level of SF-T cell hyporesponsiveness. The differential reactivity of p56(lck)
      specific monoclonal and polyclonal antibodies in SF-T but not PB-T lymphocytes
      indicated that p56(lck) modulation consists of a conformational change rather
      than loss of expression. Our results indicate that multiple signaling molecules
      can be modulated in RA SF-T cells and show for the first time a direct
      quantitative correlation between T cell hyporesponsiveness and modulation of
      TCRzeta and of p56(lck), a critical protein tyrosine kinase required for T cell
      activation.

PMID- 11222500
TI  - Heterogeneity within medullary-type TCRalphabeta(+)CD3(+)CD4(-)CD8(+) thymocytes
      in normal mouse thymus.
AB  - The functional maturation process of medullary-type CD4(-)CD8(+) [CD8 single
      positive (SP)] thymocytes remains largely uncharacterized. We describe a
      phenotypic analysis of CD8 SP medullary-type thymocytes and find a remarkable
      heterogeneity within this thymic cell population. While mature CD8(+) T cells in
      the periphery are relatively homogeneous (TCRalphabeta(+)CD3(+)Qa-2(+) HSA(
      )3G11(-)6C10(-)CD69(-)), CD8 SP medullary-type thymocytes contain discrete
      subpopulations that can be identified by differential expression of several cell
      surface markers. We have identified at least six discrete subpopulations in the
      subset of TCRalphabeta(+)CD3(+) CD8 SP cells in the thymus. According to the
      expressed phenotypes, a linear developmental pathway is predicted among these CD8
      SP subpopulations as follows: 6C10(+)CD69(+)HSA(hi)3G11(+)Qa-2(-) --> 6C10(
      )CD69(+)HSA(hi/int)3G11(+)Qa-2(-) --> 6C10(-)CD69(-)HSA(int)3G11(+)Qa-2(-) -->
      6C10(-)CD69(-)HSA(lo)3G11(+)Qa-2(-) --> 6C10(-)CD69(-)HSA(-/lo)3G11(-)Qa-2(-) -->
      6C10(-)CD69(-)HSA(-/lo)3G11(-)Qa-2(+). This study provides a framework for
      understanding CD8 SP T cell maturation in the thymic medulla.

PMID- 11222501
TI  - The non-classical MHC class I molecule Qa-1(b) inhibits classical MHC class I
      restricted cytotoxicity of cytotoxic T lymphocytes.
AB  - The CD94/NKG2A heterodimer is an inhibitory receptor expressed on a subset of
      mouse NK cells. CD94/NKG2A recognizes the non-classical MHC class I (class Ib)
      molecule Qa-1(b) and inhibits NK cytotoxicity. Qa-1(b) presents a peptide derived
      from the leader sequence of classical MHC class I molecules. Here, we examined
      the role of CD94/NKG2A in T cell-mediated cytotoxicity. Soluble tetrameric Qa
      1(b) bound to almost all CD8(+), but not CD4(+), T cells. This binding seems to
      be mediated by CD8, because COS cells transfected with CD8 also bound Qa-1(b)
      tetramer. Therefore, the expression of CD94/NKG2 in T cells was further examined
      by single-cell RT-PCR. Most murine CD8(+) T cells constitutively expressed CD94
      and NKG2A transcripts, whereas they were not detected in CD4(+) T cells. Co
      expression of Qa-1(b) and D(k) on target cells significantly inhibited
      cytotoxicity of D(k)-specific cytotoxic T lymphocytes generated by mixed
      lymphocyte reaction, indicating that Qa-1(b) on antigen-presenting cells
      interacts with CD94/NKG2A on CD8 T cells and regulates classical MHC class I
      restricted cytotoxic T cells. These results suggest a significant role of
      CD94/NKG2A as an inhibitory receptor on CD8(+) T cells.

PMID- 11222502
TI  - Correlation between eosinophilia induced by CD4(+) T cells and bronchial hyper
      responsiveness.
AB  - The relationship between CD4(+) T cell-mediated airway eosinophilic inflammation
      and bronchial hyper-responsiveness (BHR) was investigated. Ovalbumin-reactive
      T(h)0 clones were adoptively transferred to unprimed BALB/c mice and then the
      mice were challenged by inhalation of the relevant antigen. Upon antigen
      provocation, infused T(h) clones infiltrated into the airways, followed by the
      accumulation and degranulation of eosinophils, goblet cell hyperplasia, edema and
      increase in bronchial responsiveness to acetylcholine. Transfer of several clones
      that differed in the levels of IL-5 production revealed that the magnitude of in
      vivo eosinophilia strongly correlated with the IL-5-producing capacity of the
      infused T(h) clones. Administration of anti-IL-5 mAb almost completely suppressed
      antigen-induced eosinophilic inflammation and BHR. Administration of anti-IL-4
      mAb or anti-IFN-gamma mAb enhanced the eosinophilia and BHR, whereas anti-IL-2
      mAb did not affect them. The number of accumulated eosinophils significantly
      correlated with the intensity of BHR. Our present results clearly demonstrated
      that CD4(+) T cells induced BHR as a result of eosinophilic inflammation. IL-5
      totally regulated both responses.

PMID- 11222503
TI  - Induction of type 2 activity in adult human CD8(+) T cells by repeated
      stimulation and IL-4.
AB  - Repeated administration or chronic presence of antigen during CD4(+) T cell
      activation and a cytokine milieu enriched in IL-4 favour the generation and
      maintenance of a T(h)2 population. However, there is little data on how these
      factors affect adult human CD8(+) T cell functions. We established in vitro
      conditions to culture purified human CD8(+) T cells, and investigated how
      repeated stimulation and exogenous IL-4 modulated their functions. Repeated TCR
      CD3 stimulation of CD8(+) T cells increased the number of CD25-, CD30- and CD40
      ligand-expressing cells, and their capacity to secrete IL-4 and IL-5. In
      addition, repeatedly stimulated CD8(+) T cells had cytotoxic activity and
      provided help to resting B cells for IgE synthesis. The presence of exogenous IL
      4 during repeated stimulation further increased the number of CD25(+) and CD30(+)
      CD8(+) T cells, up-regulated the number of IL-5(+) cells, and increased IL-5
      levels released. These observations demonstrate that repeated TCR-CD3 stimulation
      of normal human CD8(+) T cells favoured the growth of cells with a type 2
      phenotype and that this was further amplified by the presence of IL-4. These
      mechanisms may be important in virus-induced lung eosinophilic inflammation in
      healthy subjects and virus-induced exacerbations of asthma.

PMID- 11222504
TI  - Human monoclonal anti-endothelial cell IgG-derived from a systemic lupus
      erythematosus patient binds and activates human endothelium in vitro.
AB  - Our objectives were to obtain monoclonal anti-endothelial cell antibodies (AECA)
      from systemic lupus erythematosus (SLE) patients, to characterize their antigen
      specificity, and their capability to induce a pro-inflammatory and pro-adhesive
      endothelial phenotype, and to investigate the mechanism of endothelial cell (EC)
      activation in vitro. Monoclonal IgG AECA were generated by hybridoma formation
      with human SLE B cells. Antigen specificity was characterized by immunoblotting
      with enriched cell membrane fractions, by cytofluorimetry and by cell solid-phase
      ELISA. Endothelial activation was evaluated by measuring increases in U937 cell
      adhesiveness, adhesion molecule (E-selectin and ICAM-1) expression and IL-6
      production. In addition, mechanisms of endothelial activation were investigated
      by assessment of NF-kappaB by measuring the loss of its inhibitor I-kappaB. mAb E
      3 bound live EC and recognized a 42 kDa EC membrane protein, it enhanced U937
      adhesiveness, E-selectin and ICAM-1 expression and IL-6 production, and caused
      the loss of I-kappaB. We conclude this is the first in vitro demonstration that a
      human monoclonal AECA from a SLE patient reacts with a constitutive endothelial
      membrane antigen and induces a pro-inflammatory endothelial phenotype through NF
      kappaB activation.

PMID- 11222505
TI  - CD44 binds a chondroitin sulfate proteoglycan, aggrecan.
AB  - Here we report that CD44 binds a chondroitin sulfate (CS) proteoglycan, aggrecan,
      a major component of cartilage. Soluble CD44-IgG and CD44(+) cells bound to
      aggrecan from rat chondrosarcoma and bovine cartilage, immobilized on microtiter
      plates. In both cases, binding was blocked by a neutralizing anti-CD44 mAb or by
      the pretreatment of aggrecan with chondroitinase, but not hyaluronidase or
      keratanase, indicating that CD44 binds aggrecan in a manner dependent on CS side
      chains of aggrecan and that hyaluronic acid is not involved in the binding.
      Structural analysis showed that glycosaminoglycans of aggrecan from rat
      chondrosarcoma and bovine articular cartilage consist of mainly CS A and a
      mixture of CS A and C respectively. When immobilized on microtiter plates, both
      CS A and C bound CD44-IgG, and the reaction was specifically inhibited by an anti
      CD44 mAb. In addition, aggrecan augmented apoptosis in cells expressing CD44-Fas
      chimeric molecules in synergy with a non-blocking anti-CD44 mAb IRAWB14.4,
      suggesting that CD44-aggrecan interaction can induce oligomerization of the
      chimeric molecules. These results suggest that aggrecan interacts with CD44 to
      mediate cell adhesion and to trigger oligomerization of CD44 molecules, which may
      lead to intracellular signaling.

PMID- 11222506
TI  - Comprehensive gene expression profile of human activated T(h)1- and T(h)2
      polarized cells.
AB  - In response to antigen stimulation, T(h) cells differentiate into two types of
      effector cells, T(h)1 and T(h)2. T(h)1 cells predominantly mediate cellular
      immunity, whereas T(h)2 cells induce humoral allergic responses. We have
      conducted here serial analysis of gene expression (SAGE) in human activated T(h)1
      and T(h)2-polarized cells from cord blood. SAGE analysis of 64,510 tags (32,219
      and 32,291 tags from T(h)1 and T(h)2 cells respectively) allowed identification
      of 22,096 different transcripts. In activated T(h)1 cells, many of the known
      genes (12 genes, P: < 0.01; 56 genes, P: < 0.05), including genes encoding IFN
      gamma, lymphotactin, osteopontin, MIP-1alpha, MIP-1beta, perforin, beta-catenin
      and CD55, are highly expressed. On the other hand, in activated T(h)2 cells
      rather limited numbers of known genes (four genes, P: < 0.01; 10 genes; P: <
      0.05), such as genes encoding FUS, ILF-2, IL-13 and E2-EPF, are found to be
      selectively expressed. The comprehensive identification of genes selectively
      expressed in human activated T(h)1 or T(h)2 cells should contribute to our
      understanding of the molecular basis of T(h)1/T(h)2-dominated human diseases and
      may provide genetic information to diagnose these diseases.

PMID- 11222507
TI  - CD28 co-stimulation restores T cell responsiveness in NOD mice by overcoming
      deficiencies in Rac-1/p38 mitogen-activated protein kinase signaling and IL-2 and
      IL-4 gene transcription.
AB  - Previously, we reported that T cell hyporesponsiveness induced by TCR ligation is
      causal to autoimmune diabetes in NOD mice. Neonatal CD28 co-stimulation reverses
      T cell hyporesponsiveness and protects NOD mice from diabetes by an IL-4-mediated
      mechanism, indicating that a deficiency in TCR signaling may be overcome by
      CD28/B7-2 co-stimulation in NOD T cells. To investigate which co-stimulation
      induced signaling events mediate this protection, we analyzed the activity of
      Ras, Rac-1, mitogen-activated protein kinases (MAPK) and several transcription
      factors in TCR-activated NOD T cells in the presence or absence of CD28 co
      stimulation. We show that CD28 co-stimulation restores normal TCR-induced
      activation of Rac-1 and p38 MAPK in NOD T cells. Deficiencies in TCR-induced
      nuclear expression of activating protein (AP)-1 binding proteins as well as
      activation of AP-1 and NF-AT in the IL-2 and IL-4 P1 promoters are also corrected
      by CD28 co-stimulation. Thus, CD28 co-stimulation reverses NOD T cell
      hyporesponsiveness by restoring TCR signaling leading to the activation of AP-1
      and NF-AT during IL-2 and IL-4 gene transcription. Our findings provide
      additional evidence that CD28 co-stimulation amplifies signals delivered by the
      TCR and further explain the mechanism by which CD28 co-stimulation may protect
      against autoimmune diabetes.

PMID- 11222508
TI  - Maturation of antigen-presenting cells is compromised in HLA-G transgenic mice.
AB  - The human MHC class Ib antigen HLA-G is thought to regulate maternal immune
      responses during pregnancy. Here we show that expression of HLA-G in transgenic
      mice diminished cellular immunity by inhibiting maturation of myelomonocytic
      cells into functional antigen-presenting cells (APC). Skin allografts applied to
      HLA-G transgenic mice survived longer and resultant T cell responses were less
      potent compared to control mice. T cells from HLA-G mice responded normally to
      allogeneic APC and immunohistological analyses of spleen revealed no marked
      abnormalities. However, spontaneous outgrowths of myeloid cells were observed
      when bone marrow or splenocytes from HLA-G mice were cultured in vitro, but
      functionally competent APC did not develop spontaneously in bone marrow cultures
      supplemented with granulocyte macrophage colony stimulating factor (GM-CSF).
      Addition of lipopolysaccharide (LPS) to GM-CSF-derived bone marrow cultures
      rescued APC maturation. Studies using HLA-G tetrameric reagents revealed that HLA
      G-specific binding activity was associated with CD11c(+) myelomonocytic cells,
      while binding to lymphoid and NK cell subsets was undetectable. These data show
      that spontaneous maturation of functionally competent dendritic cells (DC) is
      compromised in HLA-G mice. We hypothesize that HLA-G inhibits maturation of DC
      via receptor-mediated interactions with myelomonocytic precursors, which render
      immature DC precursors unable to receive signals from activated T cells.

PMID- 11222509
TI  - Development of cataractous macrophthalmia in mice expressing an active MEK1 in
      the lens.
AB  - PURPOSE: To characterize the extracellular signal-regulated kinase (ERK) pathway
      in the lens and to try to understand how this pathway contributes to lens
      function and cataractogenesis. METHODS: The members of the ERK pathway in the
      lens were examined by Western blotting, immunohistochemical staining, and kinase
      assay. A gain-of-function approach was used to perturb the ERK pathway in the
      lenses of transgenic mice via expression of a constitutively active mutant of the
      mitogen-activated protein kinase kinase 1 (MEK1(E)), the direct upstream kinase
      of the ERK1 and ERK2 kinases, under the alphaA-crystallin promoter. RESULTS: The
      presence of an active ERK pathway was found in lens epithelial cells and in
      differentiating fibers. Transgenic mice that expressed MEK1(E) developed
      postnatal cataracts as well as macrophthalmia. Distinct morphologic alterations,
      such as lens enlargement, swelling fiber cells, enlarged extracellular space, and
      vacuole formation, were observed in the lenses of these transgenic mice. A
      significant increase in the glucose transporter 1 (GLUT1) level, as well as in
      the glucose level, was detected in the lens. CONCLUSIONS: The MAP kinase pathway
      is involved in the regulation of glucose metabolism and balance in the mouse
      lens. Moreover, the alteration of MAP kinase activity in the lens is sufficient
      to cause cataract formation with enlarged extracellular space and vacuoles in the
      differentiating fibers. This transgenic mouse may provide a useful model for
      understanding the mechanism(s) for some aspects of human cataracts.

PMID- 11222510
TI  - Elevated expression of transglutaminase 1 and keratinization-related proteins in
      conjunctiva in severe ocular surface disease.
AB  - PURPOSE: In severe ocular surface diseases, pathologic keratinization of the
      ordinarily nonkeratinized corneal and conjunctival mucosal epithelia results in
      severe visual loss. The expression in conjunctivalized corneas of various
      proteins known to play important roles in the physiological keratinization
      process in human epidermis was examined to better understand the mechanism of
      keratinization. METHODS: Conjunctiva covering the cornea was examined in 12 eyes
      with ocular surface disease in the chronic cicatricial phase. These comprised
      four Stevens-Johnson syndrome, four ocular cicatricial pemphigoid, and four
      chemical injuries. Normal conjunctivas from four age-matched individuals served
      as controls. Semiquantitative reverse transcription-polymerase chain reaction (RT
      PCR) was used to investigate transglutaminase 1 gene expression and
      immunohistochemistry to study the expression of transglutaminase 1 protein along
      with other keratinization-related proteins (involucrin, loricrin, filaggrin, and
      cytokeratins 1 and 10) and cytokeratin pairs 4/13 and 3/12. RESULTS:
      Semiquantitative RT-PCR showed that transglutaminase 1 mRNA expression was
      upregulated in keratinized conjunctiva compared with normal. Also, in this
      tissue, immunohistochemistry demonstrated elevated levels of transglutaminase 1,
      involucrin, filaggrin, and the cytokeratin pair 1/10. Levels of loricrin and
      cytokeratin pairs 4/13 and 3/12, however, remained the same. CONCLUSIONS: Various
      keratinization-related proteins, transglutaminase 1 included, are most likely
      involved in the pathogenesis of cicatrizing ocular surface diseases.

PMID- 11222511
TI  - Effects of nicotinic antagonists on ocular growth and experimental myopia.
AB  - PURPOSE: To learn whether nicotinic cholinergic receptors modulate postnatal eye
      growth and influence the course of form-deprivation myopia. METHODS: One-week-old
      White Leghorn chicks wore a unilateral goggle to induce form-deprivation myopia.
      Other chicks were never goggled. Nicotinic antagonist drugs were administered by
      intravitreal injection, usually daily or every other day to the goggled eye or to
      one eye of never-goggled chicks. After 1 week, the eyes were studied by
      refractometry, A-scan ultrasonography, and caliper measurements. RESULTS: The
      relatively non-subtype-specific channel-blocking nicotinic antagonists
      chlorisondamine and mecamylamine each inhibited the development of form
      deprivation myopia but with complex multiphasic dose responses. Chlorisondamine
      was the most effective. Mecamylamine, at the lowest tested doses, tended to
      stimulate the growth response and myopic refractive shift of goggle wearing.
      Methyllycaconitine competitively inhibits nicotinic receptors containing the
      alpha7 and alpha8 subunits, which are highly expressed in chick retina. It showed
      a less dramatic but still significant inhibitory effect on myopia. The effects of
      dihydro-beta-erythroidine, a competitive antagonist relatively selective for
      nicotinic receptors with alpha3 or alpha4 subunits and particularly for
      alpha3beta2-containing receptors, were the weakest and inhibited primarily axial
      elongation. Chlorisondamine but not mecamylamine also affected nongoggled eyes,
      inhibiting growth and shifting refraction toward hyperopia, but chlorisondamine
      also induced degenerative changes to the retinal pigment epithelium (RPE).
      CONCLUSIONS: Nicotinic receptors are involved in eye growth control. Nicotinic
      antagonists affect the development of form-deprivation myopia and perhaps the
      growth of nongoggled eyes. The differences in drug activity and multiphasic dose
      response curves may reflect the complexity of nicotinic receptor subtypes
      associated with the eye and/or pharmacokinetic differences between the individual
      drugs. Although another tissue(s) cannot be completely excluded by these data,
      the site of action of these agents may be neural retina or RPE.

PMID- 11222512
TI  - Lacrimal drainage-associated lymphoid tissue (LDALT): a part of the human mucosal
      immune system.
AB  - PURPOSE: Mucosa-associated lymphoid tissue (MALT) specifically protects mucosal
      surfaces. In a previous study of the human conjunctiva, evidence was also found
      for the presence of MALT in the lacrimal sac. The present study, therefore, aims
      to investigate its morphology and topographical distribution in the human
      lacrimal drainage system. METHODS: Lacrimal drainage systems (n = 51) obtained
      from human cadavers were investigated by clearing flat wholemounts or by serial
      sections of tissue embedded in paraffin, OCT compound, or epoxy resin. These were
      further analyzed by histology, immunohistochemistry, and electron microscopy.
      RESULTS: All specimens showed the presence of lymphocytes and plasma cells as a
      diffuse lymphoid tissue in the lamina propria, together with intraepithelial
      lymphocytes and occasional high endothelial venules (HEV). It formed a narrow
      layer along the canaliculi that became thicker in the cavernous parts. The
      majority of lymphocytes were T cells, whereas B cells were interspersed
      individually or formed follicular centers. T cells were positive for CD8 and the
      human mucosa lymphocyte antigen (HML-1). Most plasma cells were positive for IgA
      and the overlying epithelium expressed its transporter molecule secretory
      component (SC). Basal mucous glands were present in the lacrimal canaliculi and
      in the other parts accompanied by alveolar and acinar glands, all producing IgA
      rich secretions. Primary and secondary lymphoid follicles possessing HEV were
      present in about half of the specimens. CONCLUSIONS: The term lacrimal drainage
      associated lymphoid tissue (LDALT) is proposed here to describe the lymphoid
      tissue that is regularly present and belongs to the common mucosal immune system
      and to the secretory immune system. It is suggested that it may form a functional
      unit together with the lacrimal gland and conjunctiva, connected by tear flow,
      lymphocyte recirculation, and probably the neural reflex arc, and play a major
      role in preserving ocular surface integrity.

PMID- 11222513
TI  - Differences in time course and visual requirements of ocular responses to lenses
      and diffusers.
AB  - PURPOSE: Myopia can be induced in chickens by having them wear either negative
      lenses (lens-compensation myopia [LCM]) or diffusers (form-deprivation myopia
      [FDM]), whereas positive lenses cause lens-compensation hyperopia (LCH). These
      three conditions were compared with respect to (i) their early time course and
      (ii) the effect of two manipulations of the lighting. METHODS: Longitudinal
      changes in ocular dimensions and refractive error were measured in chicks
      maintained under three different conditions: (i) wearing either -15 D lenses or
      diffusers in a normal light/dark cycle; (ii) wearing either +15 D lenses, -15 D
      lenses, or diffusers with brief periods of stroboscopic lights at the beginning
      and end of the dark period; (iii) wearing either +6 D lenses, -6 D lenses, or
      diffusers with the nights interrupted by brief periods of white light. In
      addition, scleral and choroidal proteoglycan synthesis was measured in eyes that
      wore positive lenses, negative lenses, or diffusers for 3 hours followed by
      different periods of darkness. RESULTS: (i) The time course of the changes in
      axial length over the first 72 hours was significantly faster in LCM than in FDM.
      Indeed, the diffusers did not begin to significantly affect the total length of
      the globe for 3 days, although the vitreous chamber had deepened after 9 hours,
      because the choroid thinned extremely rapidly (within 1 hour) with either
      diffusers or negative lenses. (ii) Scleral proteoglycan synthesis was higher in
      eyes with negative lenses than in those with diffusers at 11 hours, but the
      reverse was true at 27 hours. (iii) Brief periods of stroboscopic light
      attenuated FDM more than LCM. (iv) In contrast, interruption of the nights by
      brief periods of light attenuated LCM more than FDM. (v) Neither lighting
      manipulation affected LCH. (vi) Choroidal proteoglycan synthesis decreased
      similarly with 3 hours of wearing either diffusers or negative lenses.
      CONCLUSIONS: Although both negative lenses and diffusers cause similar increases
      in the rate of ocular elongation, the responses differ in time course and in the
      effect of manipulations of the daily lighting. The responses to positive lenses
      differ from both of these.

PMID- 11222514
TI  - Endogenous rhythms in axial length and choroidal thickness in chicks:
      implications for ocular growth regulation.
AB  - PURPOSE: To determine whether the diurnal rhythms in axial length and choroidal
      thickness in the chick eye are endogenous circadian rhythms. METHODS: Six
      chickens, 14 days of age, were put into darkness for 4 days. Beginning on the 3rd
      day, ocular dimensions were measured using high-frequency A-scan ultrasonography,
      in darkness, at 6-hour intervals over 48 hours. Five age-matched chickens reared
      in a normal light/dark (L/D) cycle and measured at 6-hour intervals for 5 days
      were controls. RESULTS: The rhythms in axial length and choroidal thickness
      persist in constant darkness. The phases of these rhythms are approximately in
      antiphase to one another, similar to those of eyes in a L/D cycle; however, the
      peak of the rhythm in axial length occurs slightly earlier relative to that of
      eyes in L/D (12 PM versus 3 PM; P: < 0.05, one-tailed t-test). By the 3rd day in
      darkness, the rate of growth is significantly higher than that in L/D (117 versus
      72 microm/24 hours; P: < 0.01), and the choroid becomes significantly thinner
      (159 versus 210 microm; P: < 0.0001). CONCLUSIONS: The rhythms in axial length
      and choroid thickness are circadian rhythms, driven by an endogenous oscillator.
      The phase of the rhythm in axial length in constant darkness is slightly phase
      advanced relative to eyes in L/D and thus is similar to eyes that are deprived of
      form vision. These findings suggest that in the absence of visual input, the eyes
      revert to a "default" growth state and that the similarities between the effects
      of constant darkness and of form deprivation suggest that deprivation may
      represent a type of "constant" condition.

PMID- 11222515
TI  - The relationship between opsin overexpression and photoreceptor degeneration.
AB  - PURPOSE: To characterize the process by which overexpression of normal opsin
      leads to photoreceptor degeneration. METHODS: Three transgenic mouse lines were
      generated that express different levels of an opsin with three amino acid
      modifications at the C terminus. These modifications created an epitopic site
      that can be readily distinguished from the endogenous protein using a bovine
      opsin-specific antibody. Evidence of degeneration associated with opsin
      overexpression was provided by anatomic studies and electroretinogram (ERG)
      recordings. Western blot analysis was used to confirm the production of the
      transgenic opsin, and an enzyme-linked immunosorbent assay (ELISA) was used to
      determine the amounts of opsin overexpressed in each line. Immunocytochemistry
      was used to determine the cellular localization of transgenic opsin. Amounts of
      11-cis retinal were determined by extraction and high-performance liquid
      chromatography (HPLC). RESULTS: Opsin expression levels in the three lines were
      found to be 123%, 169%, and 222% of the level measured in nontransgenic animals,
      providing direct correlation between the level of transgene expression and the
      severity of the degenerative phenotype. In the lower expressing lines, ERG a-wave
      amplitudes were reduced to less than approximately 30% and 15% of normal values,
      whereas responses of the highest expressing line were indistinguishable from
      noise. In the lowest expressor, a 26% elevation in 11-cis retinal was observed,
      whereas in the medium and the high expressors, 11-cis retinal levels were
      increased by only 30% to 33%, well below the 69% and 122% increases in opsin
      levels. CONCLUSIONS: The overexpression of normal opsin induces photoreceptor
      degeneration that is similar to that seen in many mouse models of retinitis
      pigmentosa. This degeneration can be induced by opsin levels that exceed by only
      approximately 23% that of the normal mouse retina. Opsin overexpression has
      potential implications in retinitis pigmentosa.

PMID- 11222516
TI  - The heritability of age-related cortical cataract: the twin eye study.
AB  - PURPOSE: A classical twin study was performed to establish the relative
      importance of genes and environment in cortical cataract. METHODS: Five hundred
      six pairs of unselected female twin volunteers (226 monozygotic and 280
      dizygotic) with a mean age of 62 years (range, 49-79 years) were examined.
      Cortical cataract was assessed using the slit-lamp-based Oxford Clinical Cataract
      Classification and Grading System (clinical grading) and the Wilmer Automated
      Grading System, which analyzed digital retroillumination images of subjects'
      lenses (digital grading). The worse eye categorized score for each individual was
      used in maximum likelihood path modeling of the correlations within twin pairs.
      These correlations were used to determine the underlying liability to cortical
      cataract. RESULTS: Prevalence of significant cortical cataract (>/=5% of lens
      area) was similar in monozygotic and dizygotic twins, occurring in 19.4% and
      20.6% with the clinical grading system and 24% and 23% using the digital grading
      system, respectively. Modeling suggested liability to cortical cataract is
      explained by additive and dominant genes, individual environment, and age.
      Estimates of the broad sense heritability of cortical cataract were 58% (95%
      confidence interval [CI], 51%-64%) for the clinical grading system and 53% (95%
      CI, 45%-60%) for the digital system. Dominant genes were estimated to contribute
      to 38% (95% CI, 1%-64%) of the genetic effect with the clinical grading and 53%
      (95% CI, 28%-60%) with the digital grading. Individual environment explained 26%
      and 37% and age 16% and 11% of cortical cataract variance in clinical and digital
      gradings, respectively. CONCLUSIONS: Genetic effects are important in the
      development of cortical cataract and involve the action of dominant genes.

PMID- 11222518
TI  - Relation between size at birth and age-related cataract.
AB  - PURPOSE: To determine whether poor fetal growth, as determined by size at birth,
      is associated with an increased risk of age-related cataract. METHODS: A total of
      741 men and women born in Sheffield, England between 1922 and 1930 and whose size
      at birth was available were traced and invited to take part in the study. Of
      these, 392 (53%) attended for ophthalmic examination. Lens opacity in these
      volunteers was graded using the Lens Opacities Classification System (LOCS) III.
      RESULTS: After adjusting for age, gender, gestational age, and risk factors for
      cataract there were no consistent associations between size at birth and age
      related cataract. However, the odds ratio for nuclear cataract (opalescence)
      among subjects whose birth weight was more than 8 lb was 2.4 (95% CI 1.2 to 5.0)
      compared with those who weighed under 6 lb 12 oz at birth. Risk of cortical
      cataract by contrast fell with increasing birth weight, but the trend was not
      significant and became weak after adjusting for gestational age and other risk
      factors for cataract. No relation was evident between risk of posterior
      subcapsular cataract and size at birth. CONCLUSIONS: There is no consistent
      association between size at birth and age-related cataract. The higher risk of
      nuclear cataract with increased birth weight was contrary to the expected trend.
      The apparent difference in direction of the relation between birth weight and
      different subtypes of cataract may be a chance finding but warrants further
      exploration.

PMID- 11222517
TI  - Psychometric properties of the 25-item NEI-VFQ in a Hispanic population: Proyecto
      VER.
AB  - PURPOSE: To assess the psychometric properties of the NEI-VFQ-25 in a population
      based study of older Hispanic persons living in the United States, explore other
      demographic factors that affect participant response, and observe the
      comparability of the Spanish and English versions of the instrument. METHODS: A
      sample of randomly selected block groups in Tucson and Nogales, Arizona, were
      selected for study. Participants were interviewed at home; a majority of the
      interviews were conducted in Spanish. The home interview included questions from
      the NEI-VFQ-25 and HHANES: Presenting acuity was done using ETDRS methodology,
      followed by a standardized eye examination by an ophthalmologist. The authors
      analyzed the internal consistency of the NEI-VFQ-25 responses using Cronbach's
      alpha coefficient and the construct validity by assessing the relationship
      between presenting acuity and scale scores, adjusting for age and gender. A
      second model was also explored to determine whether other demographic variables
      affected scale scores; differences in reporting between the Spanish and English
      versions was observed in this model, used in a subset of the population that
      minimized interviewer effect. RESULTS: Of the 4774 participants in the study,
      99.7% had completed questionnaires, not completed by proxy. The highest
      nonresponse rate occurred in the Driving scale, with 25% of participants not
      driving for reasons other than problems with vision. Internal consistency was
      high, with Cronbach alpha ranging between 0.65 and 0.86 for scales with multiple
      items. Adjusting for age and gender, those with presenting acuity worse than
      20/40 scored significantly lower than those with presenting acuity 20/40 or
      better, for all scales. The demographic variables with the most consistent
      association across the NEI-VFQ-25 scales were presenting acuity, income, and
      gender. No significant differences in reporting were found between the Spanish
      and English versions of the questionnaire in the subset of the population.
      CONCLUSIONS: In this study of Hispanic people age 40 years or older, the NEI-VFQ
      25 was sensitive to presenting acuity and other demographic variables, such as
      age, gender, and income. The findings from this psychometric analysis provide
      evidence of the reliability and validity of some of the scales in the 25-item NEI
      VFQ when used among people with a range of visual acuity level, providing other
      explanatory variables are also considered.

PMID- 11222519
TI  - Upper eyelid motility in blepharoptosis and in the aging eyelid.
AB  - PURPOSE: To study the metrics of lid saccades in blepharoptosis and to
      distinguish any differences in the dynamics of eyelid movements that are related
      to the cause of blepharoptosis and to aging. METHODS: The lid and vertical eye
      saccades of 7 patients with congenital blepharoptosis and those of 18 patients
      with aponeurogenic blepharoptosis, either involutional or rigid-contact-lens
      induced, were recorded with electromagnetic search coils. For each saccade, two
      parameters were assessed: amplitude and peak velocity. Two age-matched control
      groups were assessed in the same manner. Repeated measures analysis of variance
      was used to investigate any observed differences between the included groups.
      RESULTS: Congenital and rigid-contact-lens-induced blepharoptosis were readily
      distinguishable from one another, as well as from the age-matched control group,
      in both lid saccadic amplitude and peak velocity. For example, 40 degrees
      downward lid saccades in the congenital blepharoptosis group averaged 22.9
      degrees +/- 4.0 degrees (SD), whereas 30.0 degrees +/- 4.7 degrees lid saccades
      were made by the age-matched control group. The subjects in the two groups with
      aponeurogenic blepharoptosis also made lid saccades that were distinctive for
      their group (P: < 0.02), in both amplitude and peak velocity. For 40 degrees
      downward saccades in involutional and rigid-contact-lens-induced blepharoptosis,
      lid saccadic amplitude averaged 32.7 degrees +/- 4.3 degrees and 40.3 degrees +/-
      3.5 degrees, respectively. Lid saccadic peak velocity declined significantly with
      age. Lid saccadic peak velocity for 40 degrees upward saccades in the younger
      control group averaged 401.7 +/- 11.4 deg/sec, whereas the older control group
      achieved an average peak velocity of 360.7 +/- 60.4 deg/sec. The lid saccadic
      dynamics in the involutional blepharoptosis group proved to be similar (P: >
      0.05) in saccadic amplitude and peak velocity to those of age-matched controls.
      CONCLUSIONS: In different forms of blepharoptosis, distinctive metrics of lid
      saccades occur. The current data suggest that involutional blepharoptosis is not
      a consequence of normal age-related changes in eyelid function.

PMID- 11222520
TI  - Visual dysfunction between migraine events.
AB  - PURPOSE: To evaluate interictal visual dysfunction in persons with migraine in
      terms of spatiotemporal selectivity and location within the visual pathways.
      METHODS: The vision of a group of 15 persons who had experienced migraine with
      aura was compared with that of 15 normal age-matched control subjects. A range of
      thresholds was measured to evaluate precortical (background modulation, contrast
      thresholds for static, and moving stimuli), area V1 (orientation discrimination
      and motion discrimination thresholds), and higher order (global dot motion
      thresholds) visual processes. Testing was performed centrally and at 10 degrees
      in the superior visual field. For each of the tests, the spatial and temporal
      parameters of the stimuli were selected to bias detection toward either
      parvocellular or magnocellular visual mechanisms. RESULTS: No defects were found
      for parvocellular processes. Significant (P: < 0.05) losses were apparent with
      the temporal background modulation method (16 Hz), orientation discrimination
      (0.5 cyc/deg), and global dot motion tasks. CONCLUSIONS: Both cortical and
      precortical visual dysfunction were identified in migraine group 7 days after the
      headache. This loss was selective for targets with temporal modulation of
      approximately 16 Hz.

PMID- 11222521
TI  - Corneal morphology and sensitivity in lattice dystrophy type II (familial
      amyloidosis, Finnish type).
AB  - PURPOSE: To describe the corneal abnormalities and to measure different
      modalities of corneal sensitivity in corneal lattice dystrophy type II (familial
      amyloidosis, Finnish type, also known as gelsolin-related amyloidosis and
      originally as Meretoja syndrome). METHODS: Twenty eyes of 20 patients were
      examined by in vivo confocal microscopy and noncontact gas esthesiometry.
      RESULTS: Pleomorphism of, and dense deposits between or posterior to, the basal
      epithelial cells were frequently observed, as well as a reduction of long nerve
      fiber bundles in the subbasal nerve plexus. The anterior stroma was altered in
      most cases, with fibrosis and abnormal extracellular matrix. In 15 corneas, thick
      anterior and midstromal filaments, corresponding to lattice lines, and in 11
      corneas, thin undulated structures were observed. The average mechanical
      sensitivity threshold of 12 subjects was increased, and in the remaining 8
      subjects there was no response, even to the highest intensity of stimuli used.
      Three patients did not respond to CO(2), 11 to heat, and 2 to cold, but those
      patients who responded had normal thresholds. Patients with more long nerve fiber
      bundles per confocal microscopic image had better mechanical and cold sensitivity
      than patients with fewer nerve fiber bundles. CONCLUSIONS: Lattice lines seem to
      be related to amyloid material and not to corneal nerves. However, the subbasal
      nerve density appears reduced, which results mainly in a decrease in mechanical
      and, to a lesser extent, thermal sensitivity. The location of stromal filaments
      and undulated structures changes with increasing age.

PMID- 11222523
TI  - Effect of cyclosporine on conjunctival mucin in a canine keratoconjunctivitis
      sicca model.
AB  - PURPOSE: To test the hypothesis that beneficial effects of Cyclosporin A (CsA;
      Sandimmune; Sandoz, Basel, Switzerland) in treating keratoconjunctivitis sicca
      (KCS) include an effect on the mucin-producing conjunctival goblet cells
      independent of CsA's effect on lacrimation. METHODS: Keratoconjunctivitis sicca
      was induced bilaterally in six dogs after removal of orbital and nictitans
      lacrimal glands. Two weeks after induction of KCS, either 2% CsA or vehicle was
      applied twice daily to each surgically altered eye until 6 weeks after KCS
      induction. Eyes of three control dogs without surgically altered eyes were
      treated twice daily with vehicle only. Incisional biopsy specimens of ventral
      fornix conjunctiva were collected before gland removal (baseline) and at 2, 4,
      and 6 weeks after KCS induction. At each sampling time, eyes were photographed,
      and color images were subsequently graded for degree of conjunctivitis and
      characteristics of ocular discharge. Intracellular mucin stores in conjunctival
      epithelia were estimated using computer-assisted morphometry of biopsy specimen
      cross sections, and clinical and morphometric findings were correlated. RESULTS:
      Lacrimal gland removal resulted in induction of KCS in dogs by 2 weeks, with mean
      Schirmer tear test (STT) values of 5 mm/min or less occurring in surgically
      altered eyes compared with STT values of 22.5 mm/min before surgery and 22.9
      mm/min in unaltered control eyes at 2 weeks. In surgically altered eyes, STTs
      remained low during the 6-week study, independent of topical treatment.
      Intracellular mucin stores were quantified from conjunctival samples collected
      from each eye at baseline and 2, 4, and 6 weeks. At 4 and 6 weeks (after 2 and 4
      weeks of topical treatment), intraepithelial mucin quantities were significantly
      greater (P: < 0.05) in CsA-treated KCS eyes (14.4 and 13.1 microm(2)/microm,
      respectively) compared with pretreatment KCS (7.4 microm(2)/microm) eyes and
      vehicle-treated KCS eyes (7.3 and 8.5 microm(2)/microm, respectively). KCS eyes
      treated with CsA had lower conjunctivitis and ocular discharge scores than did
      vehicle-treated KCS eyes. CONCLUSIONS: Topical 2% CsA restored in vivo
      conjunctival mucin stores to control levels over a 4-week period, determined by
      computer-assisted morphometry of sequential conjunctival biopsy specimens from
      eyes of dogs with surgically induced KCS. Degree of conjunctivitis and severity
      of mucus discharge were decreased in KCS eyes treated with CsA. Because lacrimal
      tissues were removed from animals in this study, conjunctival responses occurred
      independent of lacrimogenic effect(s). These results indicate that restoration of
      conjunctival goblet cell mucin production, i.e., the balance between synthesis
      and secretion of mucin glycoproteins, may play an important role in the
      beneficial effect of CsA in treating KCS.

PMID- 11222522
TI  - Quaternary ammoniums and other preservatives' contribution in oxidative stress
      and apoptosis on Chang conjunctival cells.
AB  - PURPOSE: To investigate some of the toxicity mechanisms of 10 preservatives
      currently used in ophthalmic solutions in vitro. METHODS: A continuous human
      conjunctival cell line was treated with different concentrations of various
      preservatives for 15 minutes and for 15 minutes followed by 24 hours of cell
      recovery: three benzalkonium chlorides (BACs) with different hydrocarbon chain
      length, benzododecinium bromide (BOB), cetrimide (Cet), phenylmercuric nitrate
      (PM), thimerosal (thi), methyl parahydroxybenzoate (MPHB), chlorobutanol (clb),
      and EDTA. An inhibition study was then conducted using a 1-hour vitamin E
      pretreatment followed by a 15-minute BAC treatment. Membrane integrity was
      assessed using a neutral red test and chromatin condensation with a Hoechst 33342
      test. Reactive oxygen species were measured using dichlorofluorescein diacetate
      test for H2O2 production and hydroethidine test for O2.- production. These tests
      were performed using microplate cold light cytofluorometry. Cell size and DNA
      content were also analyzed using flow cytometry. Confocal microscopy was used to
      explore morphologic changes. RESULTS: A significant decrease of membrane
      integrity with chromatin condensation was observed with all the quaternary
      ammoniums tested at concentrations of 0.005% and higher. The effect was amplified
      after 24 hours of cell recovery. The other preservatives tested did not decrease
      membrane integrity. H2O2 production was observed with all the preservatives,
      whereas O2.- production was significantly higher with the quaternary ammoniums at
      0.005% and 0.01%, compared with the other preservatives. Flow cytometry results
      confirmed the cytotoxicity observed with cold light cytofluorometry. CONCLUSIONS:
      The quaternary ammoniums tested (BAC, BOB, and Cet) were the most cytotoxic
      preservatives in the current model. An apoptotic mechanism appeared to be present
      at low concentrations of quaternary ammoniums, whereas a necrotic process
      appeared at higher concentrations. Superoxide anions may play an important role
      in tissue damage induced by preservatives in ocular surface disorders.

PMID- 11222524
TI  - Three-dimensional Hess screen test with binocular dual search coils in a three
      field magnetic system.
AB  - PURPOSE: To establish an objective Hess screen test that allows a simultaneous
      and binocular analysis of all three axes of eye rotation. METHODS: In orthotropic
      and strabismic human subjects, both eyes were recorded with dual scleral search
      coils in a three-field magnetic system. Before mounting the search coil annuli on
      the eyes, the voltage offsets of each channel and the relative magnitudes of the
      three magnetic fields were determined. For calibration, subjects were only
      required to fix monocularly on a single reference target. During fixation of
      targets on the Hess screen by the uncovered eye, the three-dimensional eye
      position of both the occluded and the viewing eye was simultaneously measured.
      RESULTS: For clinical interpretation, an easy to understand graphical description
      of the three-dimensional Hess screen test was developed. Positions of orthotropic
      and strabismic eyes tended to follow Listing's law, which in both eyes allowed
      the determination of the primary position, that is, the position of gaze from
      which pure horizontal and pure vertical movements do not lead to an ocular
      rotation about the line-of-sight. To a first approximation, the location of
      primary position is a result of the summation of the individual rotation axes of
      the six extraocular muscles and thus can be used to infer which muscle is
      paretic. CONCLUSIONS: The three-dimensional Hess screen test with binocular dual
      search coils in a three-field magnetic system is an objective method to assess
      the ocular alignment in three dimensions with high precision. From these
      recordings, the clinician can relate deviations of primary position to specific
      eye muscle palsies.

PMID- 11222525
TI  - Cross-axis adaptation of pursuit initiation in humans.
AB  - PURPOSE: The initial acceleration of pursuit in the open-loop period is under
      adaptive control and undergoes motor learning. The current study was undertaken
      to examine the hypothesis that the direction of pursuit initiation can also be
      adaptively modified. METHODS: Four neurologically and ophthalmologically normal
      subjects participated in the experiment. A modified step-ramp paradigm was used
      to induce cross-axis adaptation, in which a ramp target changed its direction
      orthogonally just after the target crossed the center. Four direction changes
      were tested in separate experiments: left to up, left to down, down to left, and
      up to left. During a 30-minute adaptation session, the target moved in one of two
      randomly chosen directions (right to left or up to down) at one of two randomly
      chosen speeds (15.6 or 22.3 deg/sec), but the target changed orthogonally in only
      one direction. A linear regression fit to the initial 100-msec segment of the
      pursuit trace was used to determine the direction of pursuit initiation. RESULTS:
      In all cases, an adaptive change in pursuit initiation was gradually induced in
      the direction called for by the training paradigm. Adaptation was usually
      completed (90 degrees shift) within the 30-minute training session but declined
      quickly to an approximate 30 degrees -shift after training. The latency and
      vectorial amplitude of the initial acceleration remained unchanged. The
      adaptation was specific for the direction but not the velocity of the target.
      CONCLUSIONS: This study showed that the direction of pursuit initiation is under
      adaptive control, as has been shown for saccadic eye movements and the vestibulo
      ocular reflex.

PMID- 11222526
TI  - The pupil in dominant optic atrophy.
AB  - PURPOSE: To compare visual and pupil afferent function in dominant optic atrophy
      (DOA). METHODS: Patients with DOA who belonged to families showing evidence of
      linkage to the locus on chromosome 3q28-qter were recruited from the Moorfields
      Genetic Register. Patients and healthy control subjects underwent visual and
      pupil perimetry using a modified automated perimeter (Octopus 1-2-3; Interzeag,
      Schlieren, Switzerland). Five stimulus locations were tested: fixation, and at 17
      degrees eccentricity along the 45 degrees and 135 degrees meridians in all four
      quadrants. The visual deficit (difference in decibels between the patient's
      luminance threshold and that in age-matched healthy control subjects) was
      compared directly with the pupil deficit (difference in decibels between the
      stimulus intensity giving the patient's pupil response and that giving an
      equivalent pupil response in healthy control subjects) at each test location.
      RESULTS: Visual deficits and pupil afferent deficits were found at all five
      locations. The visual deficits were significantly greater than the pupil deficits
      at the four peripheral locations (median difference = 6.3 dB, P: < 0.001). At
      fixation, the difference was not significant (median difference = 2.3 dB, P: =
      0.407). CONCLUSIONS: Pupil function appears less affected than visual function at
      four of five locations tested. This result provides evidence that the
      retinotectal fibers serving the pupil light reflex are less susceptible to damage
      from the OPA1 genetic defect than the retinogeniculate fibers serving vision.

PMID- 11222527
TI  - Effect of latanoprost and timolol on the histopathology of the rabbit
      conjunctiva.
AB  - PURPOSE: Long-term medical treatment of glaucoma has an effect on the
      conjunctiva, possibly affecting the outcome of subsequent filtering surgery. The
      type and extent of these tissue changes caused by frequently used medications is
      important. An animal study using rabbits was performed to assess the tissue
      changes caused by timolol, latanoprost, and a combination of both substances.
      METHODS: Rabbits were treated with timolol, latanoprost, or a combination of
      these drugs for 18 months. Conjunctival specimens were examined by light
      microscopy, quantitative transmission electron microscopy, and
      immunohistochemistry with antibodies against matrix metalloproteinase (MMP)-3 and
      tissue inhibitors of metalloproteinase (TIMP)-2. RESULTS: By electron microscopy,
      the area of subepithelial collagen was significantly larger (P: < 0.03; Mann
      Whitney test) in timolol-treated eyes (71.6%) than in control (52.7%) and
      latanoprost-treated eyes (57.7%). An increase of amorphous material was present
      in timolol-treated eyes (25.6% versus 7.6% in the controls) as well as a smaller
      area of empty spaces (2.5% versus 39.4% in control eyes). Latanoprost-treated
      eyes had no significant increase of empty spaces but showed a marked staining for
      MMP-3 in the conjunctiva. This staining was not present in control or timolol
      treated eyes. Morphologically, degenerative changes of fibrocytes were seen in
      timolol-treated eyes only. CONCLUSIONS: A significant increase of subepithelial
      collagen density was present in timolol-treated eyes, whereas this finding was
      not apparent in latanoprost-treated eyes. Latanoprost-treated eyes showed an
      upregulation of MMP-3, which may be the reason for reduced extracellular matrix
      accumulation in such eyes. The morphologic feature of increased subepithelial
      collagen density and extracellular matrix changes may relate to failure of
      filtering blebs.

PMID- 11222528
TI  - Neuroprotective effect and intraocular penetration of nipradilol, a beta-blocker
      with nitric oxide donative action.
AB  - PURPOSE: To investigate the effect of nipradilol, an alpha(1),beta-blocker with a
      nitric oxide donative action, on N:-methyl-D-aspartate (NMDA)-induced retinal
      damage in rats and to determine whether topically instilled nipradilol penetrates
      the ipsilateral posterior retina-choroid at pharmacologically active
      concentrations in rabbits. METHODS: To determine effects on NMDA-induced damage,
      drugs were injected alone or with NMDA into the vitreous of one eye, and cell
      loss in the ganglion cell layer (GCL) and thinning of the retinal neural cell
      layers were histologically evaluated. To evaluate posterior penetration, first,
      [(14)C]-nipradilol was instilled, and its tissue concentration was measured.
      Second, nipradilol or timolol was instilled, and their effects on intravitreal
      injection of endothelin-1-induced retinal artery contraction were compared, to
      evaluate whether a pharmacologically active level of nipradilol penetrates the
      inner limiting layer by topical application. RESULTS: Intravitreous injection of
      NMDA reduced cell numbers in the GCL and the thickness of the inner plexiform
      layer (IPL) to 50.4% +/- 2.6% and 47.8% +/- 4.9% (n = 8) of control,
      respectively. Nipradilol alone had no effect. Coadministration of nipradilol with
      NMDA reduced cell numbers in the GCL and IPL thickness to 67.8% +/- 2.2% and
      74.4% +/- 5.2% of control, respectively (P: < 0.05-0.01). Sodium nitroprusside,
      but not timolol or bunazosin, also significantly prevented the NMDA-induced
      reduction of cell numbers in the GCL and IPL thickness. Radioactivity of
      nipradilol was found in the ipsilateral posterior retina-choroid at 318.6 +/-
      42.9 ng/g (n = 4), which was significantly higher than in the contralateral
      control (107.4 +/- 21.8 ng/g). Topical application of nipradilol, but not
      timolol, significantly suppressed the endothelin-1-induced contraction of the
      retinal artery (83.95% +/- 8.15% and 35.24% +/- 5.62% of baseline vessel diameter
      for nipradilol and timolol, respectively). CONCLUSIONS: Nipradilol suppressed the
      NMDA-induced retinal damage in rats for which nitric oxide released from
      nipradilol may be responsible. Posterior penetration studies suggested that an
      effective concentration of nipradilol reached the posterior retina after topical
      application.

PMID- 11222529
TI  - A new poly(ortho ester)-based drug delivery system as an adjunct treatment in
      filtering surgery.
AB  - PURPOSE: Pharmacologic modulation of wound healing after glaucoma filtering
      surgery remains a major clinical challenge in ophthalmology. Poly(ortho ester)
      (POE) is a bioerodible and biocompatible viscous polymer potentially useful as a
      sustained drug delivery system that allows the frequency of intraocular
      injections to be reduced. The purpose of this study was to determine the efficacy
      of POE containing a precise amount of 5-fluorouracil (5-FU) in an experimental
      model of filtering surgery in the rabbit. METHODS: Trabeculectomy was performed
      in pigmented rabbit eyes. An ointmentlike formulation of POE containing 1% wt/wt
      5-FU was injected subconjunctivally at the site of surgery, during the procedure.
      Intraocular pressure (IOP), bleb persistence, and ocular inflammatory reaction
      were monitored until postoperative day 30. Quantitative analysis of 5-FU was
      performed in the anterior chamber. Histologic analysis was used to assess the
      appearance of the filtering fistula and the polymer's biocompatibility. RESULTS:
      The decrease in IOP from baseline and the persistence of the filtering bleb were
      significantly more marked in the 5-FU-treated eyes during postoperative days 9
      through 28. Corneal toxicity triggered by 5-FU was significantly lower in the
      group that received 5-FU in POE compared with a 5-FU tamponade. Histopathologic
      evaluation showed that POE was well tolerated, and no fibrosis occurred in eyes
      treated with POE containing 5-FU. CONCLUSIONS: In this rabbit model of
      trabeculectomy, the formulation based on POE and containing a precise amount of 5
      FU reduced IOP and prolonged bleb persistence in a way similar to the
      conventional method of a 5-FU tamponade, while significantly reducing 5-FU
      toxicity.

PMID- 11222530
TI  - Synthesis of type II interleukin-1 receptors by human corneal epithelial cells
      but not by keratocytes.
AB  - PURPOSE: The purpose of this study was to determine whether human corneal
      epithelial cells and keratocytes synthesize both the soluble and membrane forms
      of the type II IL-1 receptor (IL-1RII). METHODS: Primary cell cultures of human
      corneal epithelial cells and keratocytes were established from human corneas. RT
      PCR was used to analyze cell cultures for expression of IL-1RII mRNA. The
      capacity of corneal cells to synthesize membrane-bound IL-1RII was determined by
      immunofluorescence microscopy, whereas ELISA was used to quantitate synthesis of
      soluble IL-1RII after IL-1alpha and TNF-alpha stimulation. RESULTS: Corneal
      epithelial cells expressed IL-1RII mRNA. The cells also stained positive for
      membrane-bound IL-1RII, and media harvested from epithelial cell cultures
      contained up to 50 pg/ml of soluble IL-1RII. Both IL-1alpha and TNF-alpha
      significantly enhanced the amounts of soluble IL-1RII released from epithelial
      cell surfaces. In contrast to epithelial cells, corneal keratocytes did not
      express IL-1RII mRNA. Membrane-bound IL-1RII was not detected on keratocytes, nor
      was soluble IL-1RII detected in culture media harvested from these cells.
      CONCLUSIONS: Human corneal epithelial cells but not corneal keratocytes
      synthesize both membrane and soluble forms of IL-1RII. Because both forms of IL
      1RII can function as IL-1alpha antagonists, the results suggest that human
      corneal epithelial cells but not corneal keratocytes have evolved the capacity to
      dampen IL-1alpha responses through the production of IL-1RII.

PMID- 11222531
TI  - Mechanisms of photoreceptor cell death in cancer-associated retinopathy.
AB  - PURPOSE: In a previous study, both recoverin and heat shock cognate protein (hsc)
      70 were recognized as autoantigens by sera from patients with cancer-associated
      retinopathy (CAR), and retinal dysfunction similar to CAR was inducible by
      intravitreous injection of anti-recoverin and anti-hsc 70 antibodies to Lewis
      rat. The purpose of the present study was to elucidate the effects of these
      antibodies on retinal photoreceptor cell functions, the contribution of caspase
      during the photoreceptor degeneration, and the roles of aberrant expression of
      recoverin in tumor cells. METHODS: As photoreceptor functions, rhodopsin
      phosphorylation using freshly prepared rod outer segments (ROS) and
      electroretinogram (ERG) were studied. Expression of recoverin in several kinds of
      tumors was examined by reverse transcription-polymerase chain reaction and
      Western blot analysis. The effects of recoverin on calcium-dependent protein
      phosphorylation were studied using the A549 lung adenocarcinoma cell line, which
      does not express recoverin. RESULTS: Rhodopsin phosphorylation in bovine ROS was
      significantly promoted by the addition of anti-recoverin antibody. Similar
      effects on rhodopsin phosphorylation and ERG impairment were observed in rat eyes
      treated with anti-recoverin antibody. Co-injection of caspase inhibitors with
      anti-recoverin antibody inhibited ERG impairment and significantly suppressed the
      antibody-induced enhancement of rhodopsin phosphorylation. Aberrant expression of
      recoverin was found in 15 of 30 tumor tissues from patients with cancer without
      CAR. Profiles of calcium-dependent protein phosphorylation of cell lysate from
      A549 cells were modulated by the presence of purified recoverin. CONCLUSIONS:
      These observations suggest that anti-recoverin antibody is incorporated into rod
      photoreceptor cells and modulates rhodopsin phosphorylation, which in turn
      produces activation of caspase-dependent apoptotic pathways. Regarding antibody
      generation in CAR, a high incidence of aberrant expression of recoverin in cancer
      tissues is important, as suggested previously.

PMID- 11222532
TI  - Regulation of nitric oxide synthase 2 in rabbit corneal cells.
AB  - PURPOSE: The purpose of these studies was to investigate the role of interferon
      gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL
      1beta), and transforming growth factor-beta (TGF-beta) in the regulation of
      inducible nitric oxide synthase (NOS2) activity in rabbit corneal cells. METHODS:
      Rabbit corneal epithelial, stromal, and endothelial cells were grown in culture
      and treated with cytokines and growth factors, alone or in combination. NOS
      activity was measured at times up to 72 hours after treatment by assaying the
      culture medium for nitrite using the Griess reaction. Cell lysates were analyzed
      by Western blot analysis for NOS2 protein. RNA was isolated and amplified with
      NOS1-, NOS2-, and NOS3-specific primers by RT-PCR. RESULTS: NOS2 expression was
      induced by combined cytokine treatment from nondetectable levels to abundant
      levels in low passage (<4) stromal cells and to low levels in corneal endothelial
      cells but not in corneal epithelial cells. In the absence of IFN-gamma, little or
      no nitrite accumulation was induced by TNF-alpha, IL-1beta, or lipopolysaccharide
      (LPS) treatment. The inductive effects of IFN-gamma were antagonized in a dose
      dependent manner by the myxoma virus rabbit IFN-gamma receptor homolog, M-T7.
      rRaIFN-gamma, in combination with IL-1beta and TNF-alpha, induced the appearance
      of NOS2 mRNA within 24 hours but detectable nitrite did not accumulate in large
      amounts (>10 microM) until after 24 hours postinduction. NOS2 was identified as a
      130 kDa protein on Western blot analysis using monoclonal antibody against murine
      NOS2. TGF-beta(1) and beta(2) inhibited the accumulation of cytokine-induced
      nitrite in a dose-dependent manner while not significantly reducing the steady
      state level of NOS2 mRNA. The activity of the induced NOS was inhibited by 1400W,
      a NOS2-selective inhibitor, but not 7-nitroindazole, a NOS1-selective inhibitor.
      CONCLUSIONS: In cultured corneal stromal cells, NOS2 expression was upregulated
      by IFN-gamma in combination with IL-1beta and TNF-alpha but not by any of these
      cytokines alone, while TGF-beta downregulated the activity. Cultures of corneal
      epithelial cells could not be induced to express NOS2, yet cultures of
      endothelial cells produced low amounts of NO in response to cytokines. The NOS1
      and NOS3 isoforms were not detected in any of these corneal cells.

PMID- 11222533
TI  - Role of recipient epithelium in promoting survival of orthotopic corneal
      allografts in mice.
AB  - PURPOSE: To determine whether epithelium-deprived corneal allografts covered with
      syngeneic epithelium display immune privilege in orthotopic transplantation and
      whether syngeneic epithelium containing antigen-presenting cells nullifies this
      effect. METHODS: Epithelium-deprived allogeneic corneas (C57BL/6) and epithelium
      deprived allogeneic corneas reconstituted with syngeneic (BALB/c) epithelium
      (containing or deprived of Langerhans' cells) were transplanted orthotopically
      into normal eyes of BALB/c mice. Graft survival was assessed clinically and
      evaluated histologically. RESULTS: Epithelium-deprived corneal grafts survived in
      syngeneic recipients but were swiftly rejected in allogeneic recipients. These
      allografts incited intense stromal inflammation and neovascularization.
      Epithelium-deprived allografts that were resurfaced in vivo by syngeneic
      epithelium derived from immune-incompetent SCID mice also underwent intense acute
      rejection when placed in normal eyes of BALB/c mice. The epithelium of in vivo
      resurfaced grafts was replete with Langerhans' cells. By contrast, most of the
      epithelium-deprived allografts reconstituted in vitro with fresh, normal BALB/c
      corneal epithelium survived indefinitely when placed in eyes of BALB/c mice.
      Similar grafts reconstituted with BALB/c epithelium containing Langerhans' cells
      were swiftly rejected. CONCLUSIONS: Replacement of donor epithelium with
      Langerhans' cell-deficient syngeneic epithelium protects orthotopic allogeneic
      cornea grafts (stroma plus endothelium) from immune-mediated rejection. The
      presence of an intact, histocompatible layer of corneal epithelium has two
      important effects on orthotopic corneal allografts: It suppresses nonspecific
      inflammation and neovascularization within the graft, and it blunts the
      alloimmunogenicity of the histoincompatible stroma and endothelium.

PMID- 11222534
TI  - Changes in adhesion complexes define stages in the differentiation of lens fiber
      cells.
AB  - PURPOSE: During their differentiation, lens fiber cells elongate, detach from the
      lens capsule, associate at the sutures, and degrade all cytoplasmic membrane
      bound organelles. Changes in the expression or organization of cell adhesion and
      cytoskeleton-associated proteins were correlated with these events during fiber
      cell differentiation in chicken embryos. METHODS: Fixed or living lenses were
      sliced with a tissue slicer, permeabilized or extracted with detergents, stained
      with antibodies or fluorescent-labeled phalloidin, and viewed with a confocal
      microscope. The distribution of N-cadherin in elongating and mature fiber cells
      was determined by Western blot analysis. Reverse transcription-polymerase chain
      reaction (RT-PCR) was used to determine the distribution of vinculin and paxillin
      transcripts. RESULTS: Staining for N-cadherin and band 4.1 protein decreased soon
      after fiber cells detached from the capsule. Detergent extraction of lens
      sections and Western blots of dissected lens regions showed that much of this
      decrease in staining was due to epitope masking. Vinculin immunoreactivity was
      barely detectable on the lateral membranes of elongating fiber cells but
      increased markedly once these cells reached their maximum length and formed the
      sutures. Staining for paxillin was also low in elongating fiber cells but
      increased late in fiber cell differentiation, just before the cells destroyed
      their membrane-bound organelles. Spectrin and ankyrin immunoreactivity did not
      change when fiber cells reached the sutures. Staining for F-actin increased
      transiently in cells that had just reached the sutures. Messenger RNAs for
      vinculin and paxillin were more abundant in maturing than in elongating fiber
      cells. CONCLUSIONS: The adhesion complexes of lens fiber cells change in
      organization and composition soon after these cells finish elongating and detach
      from the capsule. Increased staining for vinculin and paxillin defines distinct
      stages of fiber cell differentiation that are intermediate between the completion
      of cell elongation and the time when lens fiber cells degrade their membrane
      bound organelles. Remodeling adhesion complexes during fiber cell maturation may
      assure the stability of fiber-fiber associations, once these cells are no longer
      transcriptionally active.

PMID- 11222535
TI  - Development- and differentiation-dependent reorganization of intermediate
      filaments in fiber cells.
AB  - PURPOSE: To define the remodeling of lens fiber cell intermediate filaments (IF)
      that occurs with both development and differentiation. METHODS: Prenatal and
      postnatal mice were probed for the IF proteins phakosin, filensin, and vimentin,
      using light microscope immunocytochemical methodology. RESULTS: The pattern of
      vimentin accumulation in elongating fiber cells changed with development. Early
      in development vimentin first emerged predominantly as focal accumulations in the
      basal region of both epithelial and primary fiber cells. A light diffuse
      cytoplasmic staining was also noted. Later in embryonic development, and through
      maturity, vimentin in fiber cells was predominantly associated with the plasma
      membrane with no anterior-posterior polarity. Phakosin and filensin were first
      detected in the very latest stages of primary fiber elongation and continued to
      accumulate well after cells had completed elongation. Initially, these proteins
      accumulated in the anterior half of the fiber cells and were cytoplasmic in
      distribution. After P13, the pattern of initial distribution in differentiating
      fiber cells changed to a predominantly plasma membrane localization. Neither
      beaded filament protein showed focal basal accumulations. In mature lenses, all
      three proteins ultimately disappeared from the nuclear fiber cells. CONCLUSIONS:
      Beaded filament protein accumulation lags significantly behind both primary and
      secondary fiber cell elongation, suggesting a functional role subsequent to
      elongation. The subcellular distribution of vimentin and the beaded filament
      proteins showed marked differences within the cell, with differentiation, and
      with development. The differences in time of initial synthesis and in
      distribution of these IF proteins may bear on hypotheses about the role of IFs in
      fiber cell elongation and in structural-functional polarity of the fiber cell.

PMID- 11222536
TI  - Human lens thioltransferase: cloning, purification, and function.
AB  - PURPOSE: To clone the human lens thioltransferase (TTase) gene and to purify,
      characterize and study the possible function of the recombinant human lens
      thioltransferase (RHLT). METHODS: The human lens TTase gene was cloned by using
      RT-PCR and verified by sequence and RNase protection assay. TTase overexpressed
      in Escherichia coli was isolated and purified to homogeneity by column
      chromatography and identified by Western blot analysis. The activity was assayed
      with a synthetic substrate hydroxyethyl disulfide. Its function in dethiolating
      and reactivating other key metabolic enzymes was studied by using pure
      glutathione S:-transferase (GST) and glutathione peroxidase (GPx) from commercial
      source and also with the cell extract of rabbit lens epithelial cells preexposed
      to H2O2. RESULTS: The cloned human lens TTase gene showed identical sequence to
      the TTase gene from other human tissues. The RNase protection assay displayed a
      single transcript from the total RNA of human lens epithelial cells. The purified
      RHLT had a molecular weight of 11.8 kDa and reacted positively with anti-pig
      liver TTase. It displayed similar structural, functional, and kinetic
      characteristics to those of TTases from other sources. It was shown that RHLT
      effectively regenerated the activities of GST and GPx, after each was inactivated
      by S-thiolation with cystine in vitro. Furthermore, RHLT was able to restore the
      activity of the oxidatively inactivated glyceraldehyde-3-phosphate dehydrogenase
      (G-3PD) in H2O2-exposed rabbit lens epithelial cells. CONCLUSIONS: The human lens
      TTase gene has been cloned for the first time. Its gene product showed the
      characteristics which support our speculation that TTase may play a major role in
      maintaining the homeostasis of lens protein thiols thus protecting against
      oxidative stress.

PMID- 11222537
TI  - Comparison of retinal transit times and retinal blood flow: a study in monkeys.
AB  - PURPOSE: To determine the correlation between transit times of retinal blood flow
      calculated from fluorescein angiograms and retinal blood flow determined by the
      microsphere method. METHODS: Two fluorescein angiograms were obtained in each eye
      of six monkeys, followed by determination of retinal blood flow with labeled
      microspheres. Angiograms in 10 eyes were analyzed for mean transit time (MTT) and
      arteriovenous passage time (AVP). MTT was determined in two ways: from dye curves
      reconstructed by extrapolation of semilogarithmic plots of the recorded curves
      (MTT(slope)) and by a new technique based on an impulse-response analysis
      (MTT(ir)). RESULTS: Mean values (+/-SD) for retinal blood flow in 10 eyes were
      23.2 +/- 6.9 mg/min. Corresponding values for MTT(ir), MTT(slope), and AVP were
      2.22 +/- 0.38, 4.89 +/- 5.89, and 1.08 +/- 0.14 seconds. There was a weak, but
      not statistically significant, correlation between retinal blood flow and MTT(ir)
      (r = -0.60, P = 0.06) but no useful correlation between retinal blood flow and
      either MTT(slope) or AVP. CONCLUSIONS: The relationship between retinal blood
      flow and transit times determined from fluorescein angiograms is weak. Of the
      three transit parameters tested, MTT(ir), determined with the recently developed
      impulse-response technique, had the best correlation with retinal blood flow.
      Further studies are needed to determine the ability of these transit parameters
      to detect a change in retinal blood flow and the possibility that transit times
      may provide useful clinical information unrelated to absolute values of retinal
      blood flow.

PMID- 11222538
TI  - Flicker-evoked responses of human optic nerve head blood flow: luminance versus
      chromatic modulation.
AB  - PURPOSE: To determine the response of human optic nerve head blood flow
      (R:F(onh)) to heterochromatic equiluminant flicker modulation and compare it to
      the response induced by pure luminance flicker. METHODS: In five normal
      volunteers, F(onh) measured at the neuroretinal rim was monitored continuously by
      laser Doppler flowmetry. Stimuli were generated by green and red light emitting
      diodes and delivered to the fundus in Maxwellian view (field of 25(o)). Both
      green (G:) and red (R:) illuminances were square-wave modulated, 180(o) out of
      phase, with a maximum value of 10.4 for G: and 2.64 lux for R: Flicker frequency
      was varied from 2 Hz to 40 Hz. R:F(onh) was defined as the change in F(onh)
      during stimulation relative to the prestimulus F(onh). RESULTS: Defining the
      color ratio r as R:/(R: + G:), the R:F(onh), measured for a 15-Hz flicker, was
      largest at pure luminance (r = 0 and 1), declined at mixed luminance and
      chromatic modulations, and reached a secondary maximum at r = 0.45, the value of
      psychophysical equiluminance. R:F(onh) versus flicker frequency displayed the
      characteristics of a low-pass function for the equiluminance flicker stimulus and
      of a band-pass function, with a maximum at intermediate frequencies, for the
      luminance flicker stimulus. CONCLUSIONS: R:F(onh) in humans can be evoked by
      heterochromatic flicker, modulated either in luminance or chromatic equiluminant
      conditions. R:F(onh) may be specific for luminance and chromatic modulations,
      similar to neural responses dominated by the magno- and parvocellular activity,
      respectively. These findings offer a new approach to study the neurovascular
      coupling at the optic nerve head in both physiological and diseased conditions
      involving predominantly or selectively the magno- and parvocellular pathways.

PMID- 11222539
TI  - Immunocytochemical localization of NaK-ATPase isoforms in the rat and mouse
      ocular ciliary epithelium.
AB  - PURPOSE: Ion gradients established by NaK-adenosine triphosphatase (ATPase) in
      the ocular ciliary epithelium (CE) contribute to the production of aqueous humor.
      Modulation of NaK-ATPase activity in the CE may alter aqueous inflow, aqueous
      turnover, and intraocular pressure. To understand the role of NaK-ATPase, it is
      necessary to examine the distribution of NaK-ATPase subunit isoforms within the
      epithelium. METHODS: Isoform-specific antibodies and scanning laser confocal
      microscopy were used to localize NaK-ATPase subunit isoforms in the CE of the
      mouse and rat. RESULTS: The nonpigmented epithelium (NPE) expressed alpha2 and
      beta3 at very high levels on its basolateral surface, and alpha1 and beta2 at
      much lower levels. The pigmented epithelium (PE) expressed alpha1 and beta1
      subunits on its basolateral surface along its entire length, whereas alpha3 was
      expressed in the pars plana only. The distribution and apparent expression levels
      of isoforms were similar for mouse and rat, with only minor discrepancies, most
      likely caused by antibody sensitivity. CONCLUSIONS: The results indicate that
      sodium pumps in the NPE are primarily composed of alpha2 and beta3, whereas those
      in the PE are alpha1 and beta1. This specialization in isoform expression implies
      that NaK-ATPase has distinct physiological functions in the two epithelia and
      that its activity is likely to be regulated by different mechanisms.

PMID- 11222540
TI  - Electroretinographic anomalies in mice with mutations in Myo7a, the gene involved
      in human Usher syndrome type 1B.
AB  - PURPOSE: In humans, mutations in the gene encoding myosin VIIa can cause Usher
      syndrome type 1b (USH1B), a disease characterized by deafness and retinitis
      pigmentosa. Myosin VIIa is also the gene responsible for the inner ear
      abnormalities at the shaker1 (sh1) locus in mice. To date, none of the sh1
      alleles examined have shown any signs of retinal degeneration. In the present
      study, electroretinograms (ERGs) were recorded from sh1 mice to determine whether
      they have any physiological abnormalities. METHODS: ERGs were recorded from mice
      homozygous for one of nine mutant alleles of Myo7a ranging in age from postnatal
      day (P)20 to approximately 1 year. All mice were dark adapted for 30 minutes, and
      all the mutant mice were paired with an appropriately age- and strain-matched
      control animal. A presumptive null allele of myosin VIIa, Myo7a(4626SB), was used
      to determine whether mice without myosin VIIa had an increased threshold, as
      assessed by the light level required to elicit a 15-microV b-wave. RESULTS: At
      the maximum light intensity used, five of the nine alleles examined had
      significantly reduced a- and b-wave amplitudes. For example, Myo7a(4626SB) mutant
      mice had a 20% reduction in a-wave amplitude at the maximum light intensity, and
      this reduction was the same for mice ranging in age from P20 through 7 months.
      The b-wave thresholds of the Myo7a(4626SB) mutant mice were not significantly
      different from those of the control mice. Furthermore, whereas most of the
      alleles' a-wave implicit times were the same in mutant and control mice, mutant
      mice with two of the alleles had significantly faster a-wave implicit times.
      CONCLUSIONS: Mutations in myosin VIIa in mice can lead to decreased ERG
      amplitudes while threshold remains normal. This is the first report of a
      physiological anomaly in a mouse model with a mutation in the same gene as
      involved in USH1B.

PMID- 11222541
TI  - Local cone and rod system function in patients with retinitis pigmentosa.
AB  - PURPOSE: To compare local cone and rod system function in patients with retinitis
      pigmentosa (RP) using electrophysiological and psychophysical techniques.
      METHODS: Cone-mediated multifocal electroretinograms (M-ERGs), cone system
      threshold visual fields, rod-mediated M-ERGs, and rod system threshold visual
      fields were measured in seven patients with RP. RESULTS: All the patients had
      normal cone system visual field thresholds and normal cone-mediated M-ERG
      implicit times within the central 5 degrees. Both cone-mediated responses were
      abnormal at some peripheral retinal locations. There were significant
      correlations among cone system amplitude, timing, and visual field loss. All the
      patients had some retinal areas where the rod-mediated M-ERG amplitudes were not
      measurable. In areas where they were measurable, these rod-mediated M-ERG
      responses were often within normal limits for amplitude and timing. In contrast
      to the cone system data, there were no significant relationships between rod
      mediated M-ERG measures and rod system threshold elevations. The cone and rod
      system psychophysical thresholds showed regional correspondence; the amplitude
      scale and time-scale measures of the M-ERG did not. CONCLUSIONS: The results
      indicate that there was better local correspondence between psychophysical and
      electrophysiological measures in the cone system than in the rod system in
      patients with RP. In addition, the psychophysical measures of cone and rod system
      function showed better correspondence than did the electrophysiological measures.

PMID- 11222542
TI  - Sensitive blood-retinal barrier breakdown quantitation using Evans blue.
AB  - PURPOSE: This study investigated whether a nonradioactive dye, Evans blue, can be
      adapted as a safe alternative to the isotope-dilution method for quantitating
      blood-retinal barrier breakdown. METHODS: Blood-retinal barrier breakdown was
      induced in rats with vascular endothelial growth factor (VEGF) or through the
      induction of diabetes. After allowing Evans blue to circulate in the vasculature,
      the dye was cleared from the bloodstream with saline, citrate, or citrate
      buffered paraformaldehyde, and the efficacies of the perfusion solutions were
      compared. Extravasated dye was detected at 620 nm and was normalized against the
      time-averaged Evans blue plasma concentration, the circulation time, and also
      against wet and dry retina weights. RESULTS: Evans blue leakage from retinas
      treated with VEGF was 4.0-fold higher than that of contralateral untreated eyes
      (n = 6 rats, P: < 0.05). Retinal Evans blue leakage of eyes from 1-week diabetic
      animals (n = 11 retinas) was 1.7-fold higher (P: < 0.05) than that of nondiabetic
      controls (n = 10 retinas). Intra-animal, inter-retina weights showed
      significantly less variability (P: < 0.05) with the use of dry weights (11.2%, n
      = 74 retina pairs) than with wet weights (20.5%, n = 93 retina pairs).
      CONCLUSIONS: The Evans blue dye technique can be modified to be as sensitive and
      quantitative as the isotope-dilution method for measuring blood-retinal barrier
      breakdown. The advantages of the Evans blue technique are its safety, relative
      simplicity, and economy.

PMID- 11222543
TI  - Preservation of ganglion cell layer neurons in age-related macular degeneration.
AB  - PURPOSE: To determine the number of neurons remaining in the ganglion cell layer
      (GCL) of eyes with nonexudative and exudative age-related macular degeneration
      (NEAMD and EXAMD, respectively) in relation to photoreceptor loss in the same
      retinas. METHODS: The study design was a clinicopathologic correlation. Macular
      photoreceptors and GCL neurons were counted in unstained retinal wholemounts from
      eyes of patients with NEAMD (n = 6) and EXAMD (n = 5) and from control patients
      without grossly visible drusen or pigmentary change (n = 15; age range, 60-95
      years). The authors determined the percentage of counting sites with significant
      cell loss relative to control eyes and for photoreceptors, the percentage of
      sites where rod or cone loss predominated. The total numbers of cones, rods, and
      GCL neurons were determined within the 6-mm-diameter macula. Fellow eyes were
      prepared for light and electron microscopic evaluation of retinal pigment
      epithelium and Bruch's membrane disease. RESULTS: EXAMD eyes had severe
      photoreceptor loss. The total number of macular photoreceptors in NEAMD eyes was
      similar to the number in control eyes, despite moderate loss in the parafovea. In
      9 of 11 AMD eyes, rod loss was greater than cone loss at the same locations.
      EXAMD eyes had 47% fewer GCL neurons than control eyes. GCL neurons in NEAMD eyes
      did not differ significantly from control eyes. CONCLUSIONS: Interventions
      targeted at the outer retina early in the progression of neovascular disease
      should benefit from the full age-appropriate complement of GCL neurons.

PMID- 11222544
TI  - Effects of oxygen and bFGF on the vulnerability of photoreceptors to light
      damage.
AB  - PURPOSE: To test whether tissue oxygen levels affect the vulnerability of
      photoreceptors to damage by bright continuous light (BCL). METHODS: Albino rats
      were raised in standard conditions of cyclic light (12-hour light, 12-hour
      darkness) with the light level at 5 to 10 lux or 40 to 65 lux. They were then
      exposed to BCL (1000-1400 lux), either continuously for 48 hours or for the day
      or night components of the 48-hour period. During BCL, some rats were kept in
      room air (normoxia, 21% oxygen), some in hypoxia (10%), and some in hyperoxia
      (70%). Their retinas were examined for cell death, for the expression of basic
      fibroblast growth factor (bFGF), and for response to light (electroretinogram,
      ERG). RESULTS: The death of retinal cells induced by BCL was confined to
      photoreceptors. Within the retina, the severity of death was inversely related to
      the level of bFGF immunolabeling in the somas of the outer nuclear layer (ONL)
      before exposure. The death of photoreceptors was accompanied by an upregulation
      of bFGF protein levels in the ONL and by a decline in the ERG. Both hypoxia and
      hyperoxia during BCL reduced the photoreceptor death, bFGF upregulation, and ERG
      decline caused by BCL. The protective effects of hyperoxia and hypoxia were
      evident during both the day and night halves of the daily cycle. Hypoxia or
      hyperoxia alone did not upregulate bFGF or ciliary neurotrophic factor (CNTF)
      expression in the retina. CONCLUSIONS: Photoreceptors are protected from light
      damage by hypoxia and hyperoxia during exposure. The protection provided by
      oxygen levels operates during both day and night. The protection is not mediated
      by an upregulation of bFGF or CNTF.

PMID- 11222545
TI  - Expression of X-linked retinoschisis protein RS1 in photoreceptor and bipolar
      cells.
AB  - PURPOSE: To examine the biochemical properties, cell expression, and localization
      of RS1, the product of the gene responsible for X-linked juvenile retinoschisis.
      METHODS: Rs1h mRNA expression was measured from the eyes of wild-type and rd/rd
      mice by Northern blot analysis and reverse transcription-polymerase chain
      reaction (RT-PCR). Specific antibodies raised against the N terminus of RS1 were
      used as probes to examine the properties and distribution of RS1 in retina,
      retinal cell cultures, and transfected COS-1 cells by Western blot analysis and
      immunofluorescence microscopy. RESULTS: Rs1h mRNA expression was detected in the
      retina of postnatal day (P)11 and adult CD1 mice, but not homozygous rd/rd mice
      by Northern blot analysis. However, Rs1h expression was detected in rd/rd mice by
      RT-PCR. RS1 migrated as a single 24-kDa polypeptide under disulfide-reducing
      conditions and a larger complex (>95 kDa) under nonreducing conditions in the
      membrane fraction of retinal tissue homogenates and transfected COS-1 cells. RS1
      antibodies specifically stained rod and cone photoreceptors and most bipolar
      cells, but not Muller cells, ganglion cells, or the inner limiting membrane of
      adult and developing retina as revealed in double-labeling studies. RS1
      antibodies also labeled retinal bipolar cells of photoreceptorless mice and
      retinal bipolar cells grown in cell culture. CONCLUSIONS: RS1 is expressed and
      assembled in photoreceptors of the outer retina and bipolar cells of the inner
      retina as a disulfide-linked oligomeric protein complex. The secreted complex
      associates with the surface of these cells, where it may function as a cell
      adhesion protein to maintain the integrity of the central and peripheral retina.

PMID- 11222546
TI  - Mutant rhodopsin transgene expression on a null background.
AB  - PURPOSE: To study mechanisms leading to photoreceptor degeneration in mouse
      models for autosomal dominant retinitis pigmentosa (adRP) based on the rhodopsin
      P23H mutation. METHODS: Mice of a transgenic line expressing a rhodopsin triple
      mutant, V20G, P23H, and P27L (GHL), were mated with rhodopsin (rho) knockout
      mice. Littermates of various ages and genotypes (GHL+rho+/+, GHL+rho+/-, and
      GHL+rho-/-) were examined for outer nuclear layer thickness and outer segment
      formation (histology), fate of mutant rhodopsin (immunocytochemistry), and
      photoreceptor function (electroretinogram; ERG). RESULTS: Mice expressing GHL
      rhodopsin in the absence of wild-type rhodopsin had severe retinopathy, which was
      nearly complete by postnatal day (P)30. GHL-rhodopsin formed homodimers nearly
      exclusively on sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels,
      whereas wild-type rhodopsin predominantly formed monomers. Expression level of
      mutant rhodopsin in predegenerate (P10) GHL+rho-/- retinas was low, approximately
      10% to 25% of normal levels. No elaboration of disc membrane or outer segment
      formation was observed at any time point examined. The mutant rhodopsin was found
      mostly in perinuclear locales (endoplasmic reticulum; ER) as evidenced by
      colocalization using the antibodies Rho1D4 and calnexin-NT. CONCLUSIONS: GHL
      rhodopsin dimerizes, localizes to the ER, and fails to transport and support
      outer segment formation. Additionally, the mutant protein does not support a
      scotopic ERG a-wave and accelerates photoreceptor degeneration over that
      occurring with the rhodopsin knockout alone. These findings indicate a cytotoxic
      effect of the mutant protein, probably elicited by an unfolded protein response.

PMID- 11222547
TI  - Differential recovery of retinal function after mitochondrial inhibition by
      methanol intoxication.
AB  - PURPOSE: The authors' laboratory has previously documented formate-induced
      retinal toxicity in a rodent model of methanol intoxication. These studies
      determined functional, bioenergetic, and structural recovery of the retina after
      methanol intoxication. METHODS: Rats were intoxicated with methanol, and retinal
      function was assessed by electroretinography 72 hours after the initial dose of
      methanol and after a 72-hour recovery period. Retinal energy metabolites,
      glutathione (GSH) concentrations, and histology were determined at the same time
      points. RESULTS: Both rod-dominated and UV-cone-mediated electroretinogram
      responses were profoundly attenuated in methanol-intoxicated rats. In rats
      allowed to recover from methanol intoxication, there was significant, although
      incomplete, recovery of rod-dominated retinal function. However, there was no
      demonstrable improvement in UV-cone-mediated responses. Retinal adenosine
      triphosphate (ATP), adenosine diphosphate (ADP), and GSH concentrations were
      significantly reduced after intoxication. Although retinal energy metabolites
      returned to control values after the recovery period, retinal GSH remained
      significantly depleted. Histopathologic changes were apparent in the
      photoreceptors after methanol intoxication, with evidence of inner segment
      swelling and mitochondrial disruption. In animals allowed to recover from
      methanol intoxication, there was no evidence of histopathology at the light
      microscopic level; however, ultrastructural studies revealed subtle photoreceptor
      mitochondrial alterations. CONCLUSIONS: These findings support the hypothesis
      that formate inhibits retinal mitochondrial function and increases oxidative
      stress. They also provide evidence for a differential sensitivity of
      photoreceptors to the cytotoxic actions of formic acid, with a partial recovery
      of rod-dominated responses and no recovery of UV-cone-mediated responses.

PMID- 11222548
TI  - Extended photoreceptor viability by light stress in the RCS rats but not in the
      opsin P23H mutant rats.
AB  - PURPOSE: To determine the effect of light stress on retinal function and long
      term photoreceptor viability in Royal College of Surgeons (RCS) rats and the
      applicability of the light treatment to the opsin P23H mutant rats. METHODS: RCS
      rats at postnatal day (P)23 were illuminated with 120 foot-candles (fc) white
      light for 10 hours. Photoreceptor survival and basic fibroblast growth factor
      (bFGF) expression were measured at P60 and P83. Retinal function was evaluated by
      electroretinography. Opsin P23H transgenic rats were treated with light at P28
      and analyzed at P70 for photoreceptor viability, ultrastructure, and bFGF
      expression. RESULTS: Light-treated RCS rats at P60 had four to five rows of
      nuclei versus one to two rows in untreated littermates. The average amplitude of
      the ERG b-wave was 28 microV in treated rats, compared with 6 microV in untreated
      littermates. By P83 there was still significant preservation of the ONL in
      treated rats. Immunoblot analysis showed a high expression of bFGF in the treated
      retinas even 2 months after treatment. Illumination of P23H rats at P28 with 120
      fc white light for 10 hours caused substantial photoreceptor cell death, although
      bFGF expression was upregulated. Lowered illumination dosages continued to cause
      photoreceptor damage until levels were reached that neither caused damage nor
      enhanced survival. CONCLUSIONS: Although light stress promotes photoreceptor
      survival and function in the RCS rat, it elicits death signals in the P23H rats
      that may not be overcome by survival-promoting factors. Therefore, use of light
      stress to promote photoreceptor survival should be considered with regard to
      sensitivity of the mutation to light damage.

PMID- 11222549
TI  - Localization of caveolin-1 in photoreceptor synaptic ribbons.
AB  - PURPOSE: The purpose of this study is to determine whether caveolin-1 is a
      constituent of photoreceptor synaptic ribbons. METHODS: Immunoblot assay and
      electron microscopic immunocytochemistry were used to localize caveolin-1 in
      synaptic ribbons. RESULTS: Synaptic ribbons were localized close to the active
      site of presynaptic membranes and surrounded by a halo of synaptic vesicles.
      Immunosignals of caveolin-1 were clearly detected on the synaptic ribbons in rod
      and cone photoreceptors. However, the signal was seen neither on synaptic
      vesicles nor on presynaptic plasma membranes. CONCLUSIONS: Caveolin-1 is a
      component protein of synaptic ribbons and may be involved in the regulation of
      transmitter release.

PMID- 11222550
TI  - TGF-beta increases retinal endothelial cell permeability by increasing MMP-9:
      possible role of glial cells in endothelial barrier function.
AB  - PURPOSE: To determine transforming growth factor (TGF) beta effects on matrix
      metalloproteinases (MMPs) as a potential cause of the blood-retinal barrier
      breakdown at the onset of angiogenesis. Previously, glial cells were shown to
      play a role in the angiogenesis process and to express the angiogenic regulating
      factor TGF-beta, which becomes active under hypoxia conditions. Here, the authors
      demonstrate that retinal endothelial cells express MMP-9 when treated with TGF
      beta or cocultured with glial cells and that both TGF-beta and MMP-9 increase
      endothelial cell permeability. METHODS: Primary cultures of bovine retinal
      endothelial (BRE) cells grown on porous membranes were treated with TGF-beta or
      purified MMP-9, and permeability changes were assayed. The amount and
      distribution of the tight junction protein occludin also was analyzed by
      immunocytochemistry and Western blotting. Cell extracts or conditioned media from
      TGF-beta-treated BRE cells and from glial cell-BRE cocultures were analyzed for
      MMP-9 content by substrate gel electrophoresis (zymography) or Western blotting.
      RESULTS: Both TGF-beta and MMP-9 increased the permeability of BRE monolayers and
      reduced the levels of the junction protein occludin. The effect of MMP-9 on
      permeability was rapid, but the TGF-beta-induced permeability required longer
      incubation and was blocked by anti-TGF-beta and anti-MMP-9 antibodies as well as
      by TGF-beta latency-associated peptide. Zymography showed that MMP-9 activity,
      which was very low or absent in untreated BRE cultures, was dramatically
      increased by TGF-beta as well as by coculturing with either astrocytes or Muller
      glial cells. Anti-TGF-beta antibody blocked the TGF-beta effect, but not the
      coculture effect on MMP-9 production. CONCLUSIONS: These data indicate a direct
      correlation between TGF-beta-induced MMP-9 activity and increased endothelial
      cell permeability. Moreover, endothelial cell production of MMP-9 is regulated by
      glial cells through expression of TGF-beta or by direct cell-to-cell contact.
      During retinal disease, glial cell production of active TGF-beta may contribute
      to breakdown of the blood-retinal barrier by stimulating endothelial cell MMP-9
      production.

PMID- 11222551
TI  - Upregulation of P2X(7) receptor currents in Muller glial cells during
      proliferative vitreoretinopathy.
AB  - PURPOSE: Muller glial cells from the human retina express purinergic P2X(7)
      receptors. Because extracellular adenosine triphosphate (ATP) is assumed to be a
      mediator of the induction or maintenance of gliosis, this study was undertaken to
      determine whether the expression of these receptors is different in human Muller
      cells obtained from retinas of healthy donors and of patients with choroidal
      melanoma and proliferative vitreoretinopathy (PVR). METHODS: Human Muller cells
      were enzymatically isolated from donor retinas, and whole-cell patch-clamp
      recordings were made to characterize the density of the P2X(7) currents and the
      activation of currents through Ca2+-activated K+ channels of big conductance
      (I:(BK)) that reflects the increase of the intracellular Ca2+ concentration.
      RESULTS: Stimulation by external ATP or by benzoylbenzoyl ATP (BzATP) evoked both
      release of Ca2+ from thapsigargin-sensitive intracellular stores and opening of
      Ca2+ -permeable P2X(7) channels. These responses caused transient and sustained
      increases in I:(BK). In Muller cells from patients with PVR, the mean density of
      the BzATP-evoked cation currents was significantly greater compared with cells
      from healthy donors. As a consequence, such cells displayed an enlarged I:(BK)
      during application of purinergic agonists. ATP and BzATP increased the DNA
      synthesis rate of cultured cells. This effect could be reversed by blocking the
      I:(BK). CONCLUSIONS: The increased density of P2X(7) receptor channels may permit
      a higher level of entry of extracellular Ca2+ into cells from patients with PVR.
      Enhanced Ca2+ entry and the subsequent stronger activation of I:(BK) may
      contribute to the induction or maintenance of proliferative activity in gliotic
      Muller cells during PVR.

PMID- 11222552
TI  - Investigations of photoreceptor synaptic transmission and light adaptation in the
      zebrafish visual mutant nrc.
AB  - PURPOSE: To characterize the retinal physiology of the zebrafish visual mutant no
      optokinetic response c (nrc) and to identify the genetic map position of the nrc
      mutation. METHODS: Electroretinograms were recorded from wild-type and nrc
      zebrafish larvae between 5 to 6 days postfertilization. Responses to flash
      stimuli, On and Off responses to prolonged light stimuli, and responses to flash
      stimuli with constant background illumination were characterized. The glutamate
      agonist, 2-amino-4-phosphonobutyric acid (APB) was used to examine the
      photoreceptor specific a-wave component of the electroretinogram. Amplified
      fragment length polymorphism methodology was used to place the nrc mutation on
      the zebrafish genomic map. RESULTS: nrc and wild-type zebrafish larvae 5 to 6
      days postfertilization have similar threshold responses to light, but the b-wave
      of the nrc electroretinogram is significantly delayed and reduced in amplitude.
      On and Off responses of nrc larvae to prolonged light have multiple oscillations
      that do not occur in normal zebrafish larvae after 5 days postfertilization.
      Analysis of the b-wave demonstrated a light adaptation defect in nrc that causes
      saturation at background light levels approximately 1 order of magnitude less
      than those with wild-type larvae. Application of the glutamate analog, APB,
      uncovered the photoreceptor component of the electroretinogram and revealed a
      light adaptation defect in nrc photoreceptors. The nrc mutation was placed
      approximately 0.2 cM from sequence length polymorphism marker Z7504 on linkage
      group 10. CONCLUSIONS: The zebrafish mutant nrc is a possible model for human
      retinal disease. nrc has defects in photoreceptor synaptic transmission and light
      adaptation. The nrc mutant phenotype shows striking similarities with phenotypes
      of dystrophin glycoprotein complex mutants, including patients with
      Duchenne/Becker muscular dystrophy. Localization of the nrc mutation now makes it
      possible to evaluate candidate genes and clone the nrc gene.

PMID- 11222553
TI  - Contour integration deficits in anisometropic amblyopia.
AB  - PURPOSE: Previous retrospective studies have found that integration of
      orientation information along contours defined by Gabor patches is abnormal in
      strabismic, but not in anisometropic, amblyopia. This study was conducted to
      reexamine the question of whether anisometropic amblyopes have contour
      integration deficits prospectively in an untreated sample, to isolate the effects
      of the disease from the effects of prior treatment-factors that may have
      confounded the results in previous retrospective studies. METHODS: Contour
      detection thresholds, optotype acuity, and stereoacuity were measured in a group
      of 19 newly diagnosed anisometropic amblyopes before initiation of occlusion
      therapy. Contour detection thresholds were measured using a card-based procedure.
      RESULTS: Significant interocular differences in contour detection thresholds were
      present in 14 of the 19 patients with anisometropic amblyopia. CONCLUSIONS:
      Contour integration deficits are a common, but not universal, finding in
      untreated anisometropic amblyopia. Differences in the prevalence of contour
      integration deficits between the present study and that of another study may lie
      in differences in treatment history and/or in the sensitivity of the two
      different contour integration tasks.

PMID- 11222554
TI  - Spatiotemporal visual function in tinted lens wearers.
AB  - PURPOSE: Tinted lenses have been widely publicized as a successful new treatment
      for reading disorders and visual stress in children. The present study was
      designed to investigate a variety of visual deficits reported by children who
      experience high levels of visual stress and perceptual distortions when reading
      (Meares-Irlen syndrome; MIS) and to assess the improvements in visual comfort
      they report when tinted lenses are worn. METHODS: Twenty children (13.1 +/- 0.9
      years of age) were recruited who had successfully worn tinted lenses for at least
      6 months and were compared with an age-matched control group (12.6 +/- 2.2 years
      of age) of 21 children who were not lens wearers. A range of psychophysical tasks
      was adapted to identify specific anomalous visual perceptions. Spatiotemporal
      contrast sensitivity and contrast increment thresholds were used to investigate
      subjective reports of dazzle and hypercontrast, and a minimum motion perception
      (D(min)) and a motion-coherence task were used to assess subjective reports of
      visual instability and motion. RESULTS: In all viewing conditions (with versus
      without lens), no selective functional visual loss was demonstrated with any of
      the tasks used. Psychometric functions also revealed no significant difference
      between subject groups (control versus MIS). CONCLUSIONS: Under thorough
      psychophysical investigation, these results revealed no significant difference in
      visual function between subject group, and this finding is consistent with the
      absence of any effect of the tinted lenses in the group with MIS.

PMID- 11222556
TI  - Of Pseudomonas, porins, pumps and carbapenems.

PMID- 11222557
TI  - New treatments for viral respiratory tract infections--opportunities and
      problems.

PMID- 11222558
TI  - Effect of hydrophobicity and molecular mass on the accumulation of
      fluoroquinolones by Staphylococcus aureus.
AB  - Ten novel fluoroquinolones, with similar chemical structures but differing
      antibacterial activities and hydrophobicities, were studied to evaluate the role
      of the physical properties of quinolones on their accumulation and antibacterial
      activity for Staphylococcus aureus. Six of the 10 agents and tosufloxacin were
      more active against quinolone-susceptible and -resistant S. aureus than the
      remaining four agents and several piperazinyl fluoroquinolones. Changes to the
      side chains of the pyrollidinyl substituent at the R7 position alone made little
      difference to the MICs. Comparison of MICs of agents that were structurally
      identical apart from the R1 substituents, confirmed that a t-butyl group confers
      enhanced activity against S. aureus over a cyclopropyl or ethyl group at this
      position. The steady-state concentrations (SSCs) of the 10 novel quinolones
      accumulated by wild-type S. aureus did not correlate with their MICs or chemical
      structures. There was no apparent relationship between logP of the quinolone and
      accumulation by S. aureus F77; however, accumulation was positively correlated
      with molecular mass for 9/10 agents (r = 0.745) confirming that high molecular
      mass is not a barrier to accumulation in S. aureus. For all 10 agents, the
      presence of carbonyl cyanide m-chlorophenylhydrazone (CCCP) increased the
      concentration of quinolone accumulated by SA-1199, suggesting that NorA was
      inhibited. The fold increase of the SSC in the presence of CCCP did not correlate
      with hydrophobicity, but the SSC of agents with either an ethyl or cyclopropyl
      group at R1 was increased two- to three-fold in the presence of CCCP, suggesting
      that affinity for the NorA efflux pump may be influenced by quinolone structure.

PMID- 11222559
TI  - Antimicrobial activity of fluoroquinolone photodegradation products determined by
      parallel-line bioassay and high performance liquid chromatography.
AB  - The fluoroquinolones produce multiple photodegradation products. Little is known
      about these products, particularly whether any possess antimicrobial activity. To
      investigate this, we used the parallel-line bioassay to investigate discrepancies
      in zone of inhibition size in conjunction with high performance liquid
      chromatography (HPLC) analysis. A continuous flow photochemical reaction unit
      ('Beam-Boost') was used to partially photodegrade the fluoroquinolones ofloxacin,
      levofloxacin, ciprofloxacin and moxifloxacin (0.02 mM) by between 15 and 89%, as
      confirmed by HPLC. The concentration of residual parent fluoroquinolone in each
      irradiated sample was measured by HPLC and a non-irradiated control solution was
      prepared at the same concentration. These were compared by parallel-line
      bioassays using Escherichia coli, Enterobacter cloacae and Klebsiella oxytoca.
      With ofloxacin and levofloxacin, the zone size for the control solution was
      significantly less than that of the irradiated solutions, with >15%
      photodegradation in at least two of the indicator organisms, indicating that the
      photodegradation products possess antimicrobial activity. No difference was seen
      with ciprofloxacin at any level of photodegradation with any of the indicator
      organisms, nor with moxifloxacin at 30 and 54% photodegradation. A significant
      difference was observed with E. cloacae only, at 83% photodegradation.

PMID- 11222560
TI  - Fitness and competitive growth advantage of new gentamicin-susceptible MRSA
      clones spreading in French hospitals.
AB  - Since 1991, new epidemic methicillin-resistant Staphylococcus aureus (MRSA)
      strains characterized by the unexpected reappearance of heterogeneous phenotypic
      expression of resistance to methicillin and by susceptibility to gentamicin and
      various other antibiotics (GS-MRSA) have been reported in France. GS-MRSA strains
      have progressively replaced MRSA clones expressing homogeneous resistance to
      methicillin and resistance to gentamicin (GR-MRSA). In this study, we
      investigated the physiological characteristics of these new clones. In
      particular, we evaluated and compared the maximal growth rate and the deduced
      generation times (related to fitness of strains) of the major French epidemic
      MRSA clones. The population studied consisted of 79 isolates including (i) GR
      MRSA that comprised six different types on the basis of PFGE; (ii) GS-MRSA the
      majority of which clustered into two PFGE types, A1 (usually resistant to
      erythromycin) and B (usually susceptible to erythromycin); (iii) methicillin
      susceptible S. aureus (MSSA). GS-MRSA-A1 and MSSA strains were shown to have a
      significant fitness benefit (about 20%) with shorter generation times (theta =
      23.7 +/- 0.1 and 22.9 +/- 0.05 min, respectively) than GR-MRSA and GS-MRSA-B
      strains (theta = 30.3 +/- 0.2 and 32.5 +/- 0.5 min, respectively). These data
      suggest that a link exists between genetic patterns, resistance profiles and
      physiological properties. In vitro competitive experiments indicated that GS-MRSA
      A1 strains were able to rapidly outgrow GR-MRSA strains. The growth advantage
      observed should be taken into account in understanding the spread of some new
      clones of MRSA.

PMID- 11222561
TI  - Polymorphism of Neisseria meningitidis penA gene associated with reduced
      susceptibility to penicillin.
AB  - We studied polymorphism of penA (which encodes penicillin-binding protein 2) in
      13 strains of Neisseria meningitidis susceptible to penicillin (pen(S)) and 12
      strains with reduced susceptibility to penicillin (pen(I)). These strains
      differed in geographical origin. Serological and genetic typing showed that they
      were highly diverse and belonged to several genetic lineages. Restriction
      analysis and DNA sequencing of penA showed that all pen(S) strains had the same
      penA allele regardless of genetic group, whereas pen(I) strains harboured various
      penA alleles. Transformation with amplicons of penA and genomic DNA from several
      pen(I) strains conferred the pen(I) phenotype on a pen(S) strain. Thus, reduction
      in susceptibility to penicillin is directly related to changes in penA and
      analysis of penA polymorphisms could be used as a reliable tool for
      characterizing meningococcal strains in terms of their susceptibility to
      penicillin.

PMID- 11222562
TI  - Detection of mecA, mecR1 and mecI genes among clinical isolates of methicillin
      resistant staphylococci by combined polymerase chain reactions.
AB  - The distribution of the mec genes mecA, mecR1 and mecI that regulate the
      expression of methicillin resistance was investigated by PCR in 145 staphylococci
      of hospital origin. Determination of alterations and deletions in parts of the
      genes was achieved using 11 sets of primers in combined reactions. Methicillin
      resistant Staphylococcus epidermidis strains appeared relatively stable, with
      57.9% of isolates containing the whole regulatory region. Alterations within the
      mecA gene were detected more often in other coagulase-negative staphylococci,
      which also had a higher percentage with deletions of regulatory genes. Among
      methicillin-resistant S. aureus, a genetically heterogeneous population was
      identified, with several alterations and deletions of mec genes.

PMID- 11222563
TI  - Factors associated with antibiotic resistance in coliform organisms from
      community urinary tract infection in Wales.
AB  - Routine susceptibility data for urinary coliform isolates from community practice
      were analysed in comparison with dispensed antibiotic prescriptions for all
      conditions and social deprivation data for Bro Taf and North Wales Health
      Authorities for financial years 1996--1998. Prescribing rates and resistance
      rates varied widely between practices. Among isolates from practices with high
      usage of an antibiotic, rates of resistance to that antibiotic tended to be high,
      and usage correlated significantly with resistance between practice population
      units. Cross-correlations were found between usage of one antibiotic and
      resistance to another, particularly for trimethoprim and ampicillin. Usage,
      particularly of trimethoprim, was associated with multi-resistance to up to four
      antibiotics. Resistance was more frequent in isolates from males, children and
      the elderly. Ampicillin resistance correlated with social deprivation. Analyses
      including or excluding potential repeat isolates yielded closely similar results.
      Indices reflecting sampling behaviour (laboratory coliform positivity rates,
      positivity per 1000 registered patients, specimens submitted per 1000 registered
      patients) varied widely between surgeries, suggesting lack of consensus on urine
      sampling policies. These indices showed only weak correlations with usage or
      resistance. Associations between resistance and usage were compared for isolates
      from two patient subsets that were likely to differ in their proportions of non
      Escherichia coli isolates: female patients aged 16--55 years; and males, children
      and patients aged >55 years. The latter showed higher base levels of resistance,
      but the associations of resistance with usage were statistically
      indistinguishable for the two populations. The results suggest that usage of
      antibiotics in a practice population may affect the rate of urinary infection
      caused by resistant coliform organisms in that population.

PMID- 11222564
TI  - Antimicrobial resistance in salmonellae from humans, food and animals in Spain in
      1998.
AB  - We studied 1710 Salmonella: spp. isolates from human (1051), food (421) and
      animal (238) sources. They were tested by the disc diffusion method for
      susceptibility to 12 different antimicrobial agents. The incidence of resistance
      and multiple resistance (MR) among the salmonella strains of different origins,
      the relationship between their most frequent serotypes and phage types (PTs) and
      their antimicrobial resistance patterns were determined. In general, the
      incidence of resistance and MR was significantly higher in animal isolates than
      in human and food isolates (P < 0.05). Resistance to each individual drug among
      the human isolates and food isolates was very similar, with resistance to
      ampicillin, tetracycline, streptomycin and sulphonamides most frequently
      observed. MR has remained uncommon in Salmonella enteritidis. Nevertheless, 90%
      of PT6A of the human isolates and 100% of the food isolates were ampicillin
      resistant and 80 and 60%, respectively, of the PT1 isolates were nalidixic acid
      resistant. Salmonella typhimurium was the most multiresistant serotype in the
      three sample populations and ten different patterns of MR were seen. Almost 100%
      of the Salmonella hadar isolates, from human and food sources, were resistant. We
      recommend restriction of the use of antibiotics in veterinary medicine in order
      to reduce the selection and spread of multiresistant strains.

PMID- 11222565
TI  - Effects of cationic liposome-encapsulated doxycycline on experimental Chlamydia
      trachomatis genital infection in mice.
AB  - In a previous study, we demonstrated that cationic liposome-encapsulated
      doxycycline (CaL-Dox) was two-fold more effective than free doxycycline against
      Chlamydia trachomatis in vitro. Here, we evaluated the effects of two CaL-Dox
      regimens in comparison with unencapsulated doxycycline on the course of
      chlamydial genital infection in mice. Progesterone-treated, female CF-1 mice were
      challenged intravaginally with 1.2 x 10(5) inclusion-forming units (ifu) of C.
      trachomatis. Two days post-infection, the animals were divided into four
      treatment groups for im injection of doxycycline at 10 mg/kg body weight bd for 3
      (3 Dox) or 7 days (7 Dox), or of CaL-Dox at the same dose level for 3 (3 CaL-Dox)
      or 7 days (7 CaL-Dox) consecutively. An infected fifth group served as a control
      and was given an empty CaL preparation. C. trachomatis were isolated after five
      blind passages from 82% of infected control mice, 61.4% of 3 Dox, 52.2% of 3 CaL
      Dox, 29% of 7 Dox and 20% of 7 CaL-Dox animals. Histopathological reactions were
      found in various tissues of the genital tract in 79.5% of infected control mice,
      80.9% of 3 Dox, 65.2% of 3 CaL-Dox, 47.1% of 7 Dox and 25.7% of 7 CaL-Dox
      animals. Total antichlamydial antibody titres were lower in 7 CaL-Dox mice than
      in all the other groups (P < 0.005). The results showed that progesterone-treated
      CF-1 mice are suitable for investigation of both lower and upper genital tract
      infection with a lymphogranuloma venereum biovar strain of C. trachomatis.
      Neither 7 CaL-Dox nor 3 CaL-Dox treatment was more effective than unencapsulated
      7 Dox doses in the bacteriological cure of chlamydial genital infection in mice.
      However, 7 CaL-Dox prevented tissue damage in the genital tract significantly
      more than all the other regimens (P < 0.05). These results suggest that liposome
      encapsulated doxycycline, particularly CaL-Dox, may have potential for the
      clinical treatment of chlamydial infections.

PMID- 11222566
TI  - Acquired itraconazole resistance in Aspergillus fumigatus.
AB  - The antifungal susceptibility profiles of four ASPERGILLUS: fumigatus isolates,
      recovered at different times from a patient treated with itraconazole for a
      pulmonary ASPERGILLUS: infection, were evaluated. Itraconazole MICs against two
      pre-treatment isolates were 0.5 mg/L, whilst two later isolates, recovered after
      at least 4 months of itraconazole therapy, had itraconazole MICs of >16 mg/L. In
      vivo susceptibilities to itraconazole and amphotericin B were tested in a murine
      model of disseminated aspergillosis. Treatment efficacy was evaluated by
      examining mortality rates and qualitative cultures of brain and kidneys.
      Itraconazole therapy significantly prolonged survival of mice infected with the
      initial isolates as compared with untreated controls. The third isolate was only
      partially susceptible to itraconazole in vivo, and the fourth isolate was highly
      resistant. The four isolates were typed by random amplified polymorphic DNA
      (RAPD) with four different primers. RAPD patterns obtained with each of them were
      identical, suggesting that the same strain was recovered over time and had
      acquired resistance to itraconazole.

PMID- 11222567
TI  - Characterization of high-level fluoroquinolone resistance in Escherichia coli
      O78:K80 isolated from turkeys.
AB  - Fluoroquinolone resistance was characterized in Escherichia coli O78:K80 isolated
      from diseased turkeys. The level of resistance to fluoroquinolones of the
      isolates appeared closely correlated with substitutions in GyrA and ParC, but not
      with the production of the AcrAB efflux pump. Among isolates highly resistant to
      ciprofloxacin (MIC 8 mg/L) and harbouring identical substitutions (two in GyrA
      and one in ParC), two close but distinguishable ribotypes were identified. This
      indicated that at least two independent selection events may have occurred.

PMID- 11222568
TI  - Phenotypic and genotypic characterization of macrolide-resistant group A
      Streptococcus strains in the province of Quebec, Canada.
AB  - Resistance to macrolides among group A streptococci is an increasing problem
      worldwide. We examined 496 strains phenotypically and genotypically for
      resistance to erythromycin and clindamycin. Strains were isolated in five
      different geographical areas representing about 45% of the total Quebec
      population. The overall resistance rate was 4.6% but varied from 0% in rural
      areas to 9.4% in Montreal. Of the 23 strains showing resistance to erythromycin,
      15 (65%) had an identical pulsed-field gel electrophoresis pattern, were of
      serotype M28T28 and harboured the erm(TR) gene, suggesting the spread of a single
      clone. Of the remaining eight strains, two strains had the erm(B) gene, five had
      the mef gene and one with a different serotype also had the erm(TR) gene.

PMID- 11222569
TI  - Efficacy of linezolid in a staphylococcal endocarditis rabbit model.
AB  - A rabbit endocarditis model was used to test the efficacy of oral linezolid and
      iv vancomycin. Twenty-four hours after catheter placement across the aortic
      valve, rabbits were infected with 3.5 x 10(6) cfu of Staphylococcus aureus (UC
      9258). Two days after infection, control rabbits were killed, and treated rabbits
      were given 5 days of therapy with linezolid at 8 h intervals (tds) using either
      25, 50 or 75 mg/kg/dose, or vancomycin at 12 h intervals (bd) using 25
      mg/kg/dose. Linezolid at 75 and 50 mg/kg, and vancomycin significantly reduced S.
      aureus in aortic valve vegetations compared with the control. Linezolid at 25
      mg/kg was ineffective. The efficacy of 75 and 50 mg/kg linezolid was related to
      maintenance of plasma drug levels near or above the linezolid MIC for UC-9258 (2
      mg/L).

PMID- 11222571
TI  - Detection of glycopeptide resistance in Staphylococcus aureus.

PMID- 11222570
TI  - A phase I/II study of the safety and activity of a microsphere formulation of KNI
      272 in patients with HIV-1 infection.
AB  - Eighteen patients with symptomatic HIV disease were enrolled into a phase I/II
      study of a microsphere formulation of the HIV protease inhibitor KNI-272, with
      doses escalated up to a maximum dose of 60 mg/kg/day. One patient developed
      reversible elevation in hepatic transaminase. The plasma half-life of the drug
      was very short, varying between 0.25 and 1.1 h. No consistent effect on plasma
      HIV RNA levels or CD4(+) lymphocyte counts was seen.

PMID- 11222572
TI  - Clarithromycin and risk of Clostridium difficile-associated diarrhoea.

PMID- 11222573
TI  - The activity of antibiotics against Legionella pneumophila: in vitro and in vivo
      studies.

PMID- 11222574
TI  - In vitro activity of gemifloxacin against Helicobacter pylori.

PMID- 11222575
TI  - In vitro susceptibility of Vibrio cholerae O1 biotype El Tor strains associated
      with an outbreak of cholera in Kerala, Southern India.

PMID- 11222576
TI  - Bacteraemia due to vancomycin-resistant enterococci in Slovakia.

PMID- 11222577
TI  - Daptomycin for line-related Leuconostoc bacteraemia.

PMID- 11222578
TI  - Subdural empyema caused by Prevotella loescheii with reduced susceptibility to
      metronidazole.

PMID- 11222579
TI  - Prescribing quality is not synonymous with cost minimization for antibiotics.

PMID- 11222581
TI  - Sigma(B) activity depends on RsbU in Staphylococcus aureus.
AB  - Derivatives of the widely used laboratory strain Staphylococcus aureus NCTC8325,
      which are natural rsbU mutants, were shown to be unable to produce RsbU, a
      positive regulator of the alternative sigma factor sigma(B). The lack of RsbU
      prevented the heat-dependent production of sigma(B)-controlled transcripts and
      resulted in reduced H2O2 and UV tolerance, enhanced alpha-hemolysin activity, and
      the inability to produce the alkaline shock protein Asp23. After 48 h of growth,
      rsbU mutant strains failed to accumulate staphyloxanthin, the major stationary
      phase carotenoid. Transcription of Asp23 was found to be exclusively controlled
      by sigma(B), making it an excellent target for the study of sigma(B) activity in
      S. aureus. Reporter gene experiments, using the firefly luciferase gene (luc+)
      fused to the sigma(B)-dependent promoter(s) of asp23, revealed that sigma(B) is
      almost inactive in 8325 derivatives. cis complementation of the 8325 derivative
      BB255 with the wild-type rsbU gene from strain COL produced the rsbU(+)
      derivative GP268, a strain possessing a sigma(B) activity profile comparable to
      that of the rsbU(+) wild-type strain Newman. In GP268, the heat inducibility of
      sigma(B)-dependent genes, Asp23 production, alpha-hemolysin activity,
      pigmentation, and susceptibility to H2O2 were restored to the levels observed in
      strain Newman, clearly demonstrating that RsbU is needed for activation of
      sigma(B) in S. aureus.

PMID- 11222580
TI  - The pleiotropic two-component regulatory system PhoP-PhoQ.

PMID- 11222582
TI  - Degenerative minimalism in the genome of a psyllid endosymbiont.
AB  - Psyllids, like aphids, feed on plant phloem sap and are obligately associated
      with prokaryotic endosymbionts acquired through vertical transmission from an
      ancestral infection. We have sequenced 37 kb of DNA of the genome of Carsonella
      ruddii, the endosymbiont of psyllids, and found that it has a number of unusual
      properties revealing a more extreme case of degeneration than was previously
      reported from studies of eubacterial genomes, including that of the aphid
      endosymbiont Buchnera aphidicola. Among the unusual properties are an
      exceptionally low guanine-plus-cytosine content (19.9%), almost complete absence
      of intergenic spaces, operon fusion, and lack of the usual promoter sequences
      upstream of 16S rDNA. These features suggest the synthesis of long mRNAs and
      translational coupling. The most extreme instances of base compositional bias
      occur in the genes encoding proteins that have less highly conserved amino acid
      sequences; the guanine-plus-cytosine content of some protein-coding sequences is
      as low as 10%. The shift in base composition has a large effect on proteins: in
      polypeptides of C. ruddii, half of the residues consist of five amino acids with
      codons low in guanine plus cytosine. Furthermore, the proteins of C. ruddii are
      reduced in size, with an average of about 9% fewer amino acids than in homologous
      proteins of related bacteria. These observations suggest that the C. ruddii
      genome is not subject to constraints that limit the evolution of other known
      eubacteria.

PMID- 11222583
TI  - T7 single strand DNA binding protein but not T7 helicase is required for DNA
      double strand break repair.
AB  - An in vitro system based on Escherichia coli infected with bacteriophage T7 was
      used to test for involvement of host and phage recombination proteins in the
      repair of double strand breaks in the T7 genome. Double strand breaks were placed
      in a unique XhoI site located approximately 17% from the left end of the T7
      genome. In one assay, repair of these breaks was followed by packaging DNA
      recovered from repair reactions and determining the yield of infective phage. In
      a second assay, the product of the reactions was visualized after electrophoresis
      to estimate the extent to which the double strand breaks had been closed. Earlier
      work demonstrated that in this system double strand break repair takes place via
      incorporation of a patch of DNA into a gap formed at the break site. In the
      present study, it was found that extracts prepared from uninfected E. coli were
      unable to repair broken T7 genomes in this in vitro system, thus implying that
      phage rather than host enzymes are the primary participants in the predominant
      repair mechanism. Extracts prepared from an E. coli recA mutant were as capable
      of double strand break repair as extracts from a wild-type host, arguing that the
      E. coli recombinase is not essential to the recombinational events required for
      double strand break repair. In T7 strand exchange during recombination is
      mediated by the combined action of the helicase encoded by gene 4 and the
      annealing function of the gene 2.5 single strand binding protein. Although a
      deficiency in the gene 2.5 protein blocked double strand break repair, a gene 4
      deficiency had no effect. This argues that a strand transfer step is not required
      during recombinational repair of double strand breaks in T7 but that the ability
      of the gene 2.5 protein to facilitate annealing of complementary single strands
      of DNA is critical to repair of double strand breaks in T7.

PMID- 11222584
TI  - Molecular characterization of global regulatory RNA species that control
      pathogenicity factors in Erwinia amylovora and Erwinia herbicola pv. gypsophilae.
AB  - rsmB(Ecc) specifies a nontranslatable RNA regulator that controls exoprotein
      production and pathogenicity in soft rot-causing Erwinia carotovora subsp.
      carotovora. This effect of rsmB(Ecc) RNA is mediated mostly by neutralizing the
      function of RsmA(Ecc), an RNA-binding protein of E. carotovora subsp. carotovora,
      which acts as a global negative regulator. To determine the occurrence of
      functional homologs of rsmB(Ecc) in non-soft-rot-causing Erwinia species, we
      cloned the rsmB genes of E. amylovora (rsmB(Ea)) and E. herbicola pv. gypsophilae
      (rsmB(Ehg)). We show that rsmB(Ea) in E. amylovora positively regulates
      extracellular polysaccharide (EPS) production, motility, and pathogenicity. In E.
      herbicola pv. gypsophilae, rsmB(Ehg) elevates the levels of transcripts of a
      cytokinin (etz) gene and stimulates the production of EPS and yellow pigment as
      well as motility. RsmA(Ea) and RsmA(Ehg) have more than 93% identity to RsmA(Ecc)
      and, like the latter, function as negative regulators by affecting the transcript
      stability of the target gene. The rsmB genes reverse the negative effects of
      RsmA(Ea), RsmA(Ehg), and RsmA(Ecc), but the extent of reversal is highest with
      homologous combinations of rsm genes. These observations and findings that
      rsmB(Ea) and rsmB(Ehg) RNA bind RsmA(Ecc) indicate that the rsmB effect is
      channeled via RsmA. Additional support for this conclusion comes from the
      observation that the rsmB genes are much more effective as positive regulators in
      a RsmA(+) strain of E. carotovora subsp. carotovora than in its RsmA(-)
      derivative. E. herbicola pv. gypsophilae produces a 290-base rsmB transcript that
      is not subject to processing. By contrast, E. amylovora produces 430- and 300
      base rsmB transcripts, the latter presumably derived by processing of the primary
      transcript as previously noted with the transcripts of rsmB(Ecc). Southern blot
      hybridizations revealed the presence of rsmB homologs in E. carotovora, E.
      chrysanthemi, E. amylovora, E. herbicola, E. stewartii and E. rhapontici, as well
      as in other enterobacteria such as Escherichia coli, Salmonella enterica serovar
      Typhimurium, Serratia marcescens, Shigella flexneri, Enterobacter aerogenes,
      Klebsiella pneumoniae, Yersinia enterocolitica, and Y. pseudotuberculosis. A
      comparison of rsmB sequences from several of these enterobacterial species
      revealed a highly conserved 34-mer region which is predicted to play a role in
      positive regulation by rsmB RNA.

PMID- 11222585
TI  - Quantitation of the capacity of the secretion apparatus and requirement for PrsA
      in growth and secretion of alpha-amylase in Bacillus subtilis.
AB  - Regulated expression of AmyQ alpha-amylase of Bacillus amyloliquefaciens was used
      to examine the capacity of the protein secretion apparatus of B. subtilis. One B.
      subtilis cell was found to secrete maximally 10 fg of AmyQ per h. The signal
      peptidase SipT limits the rate of processing of the signal peptide. Another limit
      is set by PrsA lipoprotein. The wild-type level of PrsA was found to be 2 x 10(4)
      molecules per cell. Decreasing the cellular level of PrsA did not decrease the
      capacity of the protein translocation or signal peptide processing steps but
      dramatically affected secretion in a posttranslocational step. There was a linear
      correlation between the number of cellular PrsA molecules and the number of
      secreted AmyQ molecules over a wide range of prsA and amyQ expression levels.
      Significantly, even when amyQ was expressed at low levels, overproduction of PrsA
      enhanced its secretion. The finding is consistent with a reversible interaction
      between PrsA and AmyQ. The high cellular level of PrsA suggests a chaperone-like
      function. PrsA was also found to be essential for the viability of B. subtilis.
      Drastic depletion of PrsA resulted in altered cellular morphology and ultimately
      in cell death.

PMID- 11222586
TI  - Involvement of a CbbR homolog in low CO2-induced activation of the bicarbonate
      transporter operon in cyanobacteria.
AB  - The cmpABCD operon of Synechococcus sp. strain PCC 7942, encoding a high-affinity
      bicarbonate transporter, is transcribed only under CO2-limited conditions. In
      Synechocystis sp. strain PCC 6803, the slr0040, slr0041, slr0043, and slr0044
      genes, forming an operon with a putative porin gene (slr0042), were identified as
      the cmpA, cmpB, cmpC, and cmpD genes, respectively, on the basis of their strong
      similarities to the corresponding Synechococcus cmp genes and their induction
      under low CO2 conditions. Immediately upstream of and transcribed divergently
      from the Synechocystis cmp operon is a gene (sll0030) encoding a homolog of CbbR,
      a LysR family transcriptional regulator of the CO2 fixation operons of
      chemoautotrophic and purple photosynthetic bacteria. Inactivation of sll0030, but
      not of another closely related cbbR homolog (sll1594), abolished low CO2
      induction of cmp operon expression. Gel retardation assays showed specific
      binding of the Sll0030 protein to the sll0030-cmpA intergenic region, suggesting
      that the protein activates transcription of the cmp operon by interacting with
      its regulatory region. A cbbR homolog similar to sll0030 and sll1594 was cloned
      from Synechococcus sp. strain PCC 7942 and shown to be involved in the low CO2
      induced activation of the cmp operon. We hence designated the Synechocystis
      sll0030 gene and the Synechococcus cbbR homolog cmpR. In the mutants of the cbbR
      homologs, upregulation of ribulose-1,5-bisphosphate carboxylase/oxygenase operon
      expression by CO2 limitation was either unaffected (strain PCC 6803) or enhanced
      (strain PCC 7942), suggesting existence of other low CO2-responsive
      transcriptional regulator(s) in cyanobacteria.

PMID- 11222587
TI  - Reinvestigation of a new type of aerobic benzoate metabolism in the
      proteobacterium Azoarcus evansii.
AB  - The aerobic metabolism of benzoate in the proteobacterium Azoarcus evansii was
      reinvestigated. The known pathways leading to catechol or protocatechuate do not
      operate in this bacterium. The presumed degradation via 3-hydroxybenzoyl-coenzyme
      A (CoA) and gentisate could not be confirmed. The first committed step is the
      activation of benzoate to benzoyl-CoA by a specifically induced benzoate-CoA
      ligase (AMP forming). This enzyme was purified and shown to differ from an
      isoenzyme catalyzing the same reaction under anaerobic conditions. The second
      step postulated involves the hydroxylation of benzoyl-CoA to a so far unknown
      product by a novel benzoyl-CoA oxygenase, presumably a multicomponent enzyme
      system. An iron-sulfur flavoprotein, which may be a component of this system, was
      purified and characterized. The homodimeric enzyme had a native molecular mass of
      98 kDa as determined by gel filtration and contained 0.72 mol flavin adenine
      dinucleotide (FAD), 10.4 to 18.4 mol of Fe, and 13.3 to 17.9 mol of acid-labile
      sulfur per mol of native protein, depending on the method of protein
      determination. This benzoate-induced enzyme catalyzed a benzoyl-CoA-, FAD-, and
      O2-dependent NADPH oxidation surprisingly without hydroxylation of the aromatic
      ring; however, H2O2 was formed. The gene (boxA, for benzoate oxidation) coding
      for this protein was cloned and sequenced. It coded for a protein of 46 kDa with
      two amino acid consensus sequences for two [4Fe-4S] centers at the N terminus.
      The deduced amino acid sequence showed homology with subunits of ferredoxin-NADP
      reductase, nitric oxide synthase, NADPH-cytochrome P450 reductase, and phenol
      hydroxylase. Upstream of the boxA gene, another gene, boxB, encoding a protein of
      55 kDa was found. The boxB gene exhibited homology to open reading frames in
      various other bacteria which code for components of a putative aerobic
      phenylacetyl-CoA oxidizing system. The boxB gene product was one of at least five
      proteins induced when A. evansii was grown on benzoate.

PMID- 11222588
TI  - Analysis of the pmsCEAB gene cluster involved in biosynthesis of salicylic acid
      and the siderophore pseudomonine in the biocontrol strain Pseudomonas fluorescens
      WCS374.
AB  - Mutants of Pseudomonas fluorescens WCS374 defective in biosynthesis of the
      fluorescent siderophore pseudobactin still display siderophore activity,
      indicating the production of a second siderophore. A recombinant cosmid clone
      (pMB374-07) of a WCS374 gene library harboring loci necessary for the
      biosynthesis of salicylic acid (SA) and this second siderophore pseudomonine was
      isolated. The salicylate biosynthesis region of WCS374 was localized in a 5-kb
      EcoRI fragment of pMB374-07. The SA and pseudomonine biosynthesis region was
      identified by transfer of cosmid pMB374-07 to a pseudobactin-deficient strain of
      P. putida. Sequence analysis of the 5-kb subclone revealed the presence of four
      open reading frames (ORFs). Products of two ORFs (pmsC and pmsB) showed
      homologies with chorismate-utilizing enzymes; a third ORF (pmsE) encoded a
      protein with strong similarity with enzymes involved in the biosynthesis of
      siderophores in other bacterial species. The region also contained a putative
      histidine decarboxylase gene (pmsA). A putative promoter region and two predicted
      iron boxes were localized upstream of pmsC. We determined by reverse
      transcriptase-mediated PCR that the pmsCEAB genes are cotranscribed and that
      expression is iron regulated. In vivo expression of SA genes was achieved in P.
      putida and Escherichia coli cells. In E. coli, deletions affecting the first ORF
      (pmsC) diminished SA production, whereas deletion of pmsB abolished it
      completely. The pmsB gene induced low levels of SA production in E. coli when
      expressed under control of the lacZ promoter. Several lines of evidence indicate
      that SA and pseudomonine biosynthesis are related. Moreover, we isolated a Tn5
      mutant (374-05) that is simultaneously impaired in SA and pseudomonine
      production.

PMID- 11222589
TI  - The -10 region is a key promoter specificity determinant for the Bacillus
      subtilis extracytoplasmic-function sigma factors sigma(X) and sigma(W).
AB  - Transcriptional selectivity derives, in large part, from the sequence-specific
      DNA-binding properties of the sigma subunit of RNA polymerase. There are 17 sigma
      factors in Bacillus subtilis which, in general, recognize distinct sets of
      promoters. However, some sigma factors have overlapping promoter selectivity. We
      hypothesize that the overlap between the regulons activated by the sigma(X) and
      sigma(W) factors can be explained by overlapping specificity for the -10 region:
      sigma(X) recognizes -10 elements with the sequence CGAC and sigma(W) recognizes
      CGTA, while both can potentially recognize CGTC. To test this model, we mutated
      the sigma(X)-specific autoregulatory site (P(X)), containing the -10 element
      CGAC, to either CGTC or GCTA. Conversely, the sigma(W) autoregulatory site (P(W))
      was altered from CGTA to CGTC or CGAC. Transcriptional analyses, both in vitro
      and in vivo, indicate that changes to the -10 element are sufficient to switch a
      promoter from the sigma(X) to the sigma(W) regulon or, conversely, from the
      sigma(W) to the sigma(X) regulon, but context effects clearly play an important
      role in determining promoter strength. It seems likely that these subtle
      differences in promoter selectivity derive from amino acid differences in
      conserved region 2 of sigma, which contacts the -10 element. However, we were
      unable to alter promoter selectivity by replacements of two candidate recognition
      residues in sigma(W).

PMID- 11222590
TI  - Complete genomic sequence of the lytic bacteriophage phiYeO3-12 of Yersinia
      enterocolitica serotype O:3.
AB  - phiYeO3-12 is a T3-related lytic bacteriophage of Yersinia enterocolitica
      serotype O:3. The nucleotide sequence of the 39,600-bp linear double-stranded DNA
      (dsDNA) genome was determined. The phage genome has direct terminal repeats of
      232 bp, a GC content of 50.6%, and 54 putative genes, which are all transcribed
      from the same DNA strand. Functions were assigned to 30 genes based on the
      similarity of the predicted products to known proteins. A striking feature of the
      phiYeO3-12 genome is its extensive similarity to the coliphage T3 and T7 genomes;
      most of the predicted phiYeO3-12 gene products were >70% identical to those of
      T3, and the overall organizations of the genomes were similar. In addition to an
      identical promoter specificity, phiYeO3-12 shares several common features with
      T3, nonsubjectibility to F exclusion and growth on Shigella sonnei D(2)371-48 (M.
      Pajunen, S. Kiljunen, and M. Skurnik, J. Bacteriol. 182:5114-5120, 2000). These
      findings indicate that phiYeO3-12 is a T3-like phage that has adapted to Y.
      enterocolitica O:3 or vice versa. This is the first dsDNA yersiniophage genome
      sequence to be reported.

PMID- 11222591
TI  - Involvement of ResE phosphatase activity in down-regulation of ResD-controlled
      genes in Bacillus subtilis during aerobic growth.
AB  - The ResD-ResE signal transduction system is required for aerobic and anaerobic
      respiration in Bacillus subtilis. The histidine sensor kinase ResE, by
      functioning as a kinase and a phosphatase for the cognate response regulator
      ResD, controls the level of phosphorylated ResD. A high level of phosphorylated
      ResD is postulated to cause a dramatic increase in transcription of ResDE
      controlled genes under anaerobic conditions. A mutant ResE, which retains
      autophosphorylation and ResD phosphorylation activities but is defective in ResD
      dephosphorylation, allowed partially derepressed aerobic expression of the ResDE
      controlled genes. The result indicates that phosphatase activity of ResE is
      regulated by oxygen availability and anaerobic induction of the ResDE regulon is
      partly due to a reduction of the ResE phosphatase activity during anaerobiosis.
      That elimination of phosphatase activity does not result in complete aerobic
      derepression suggests that the ResE kinase activity is also subject to control in
      response to oxygen limitation.

PMID- 11222592
TI  - Cellulosomal scaffoldin-like proteins from Ruminococcus flavefaciens.
AB  - Two tandem cellulosome-associated genes were identified in the cellulolytic rumen
      bacterium, Ruminococcus flavefaciens. The deduced gene products represent
      multimodular scaffoldin-related proteins (termed ScaA and ScaB), both of which
      include several copies of explicit cellulosome signature sequences. The scaB gene
      was completely sequenced, and its upstream neighbor scaA was partially sequenced.
      The sequenced portion of scaA contains repeating cohesin modules and a C-terminal
      dockerin domain. ScaB contains seven relatively divergent cohesin modules, two
      extremely long T-rich linkers, and a C-terminal domain of unknown function.
      Collectively, the cohesins of ScaA and ScaB are phylogenetically distinct from
      the previously described type I and type II cohesins, and we propose that they
      define a new group, which we designated here type III cohesins. Selected modules
      from both genes were overexpressed in Escherichia coli, and the recombinant
      proteins were used as probes in affinity-blotting experiments. The results
      strongly indicate that ScaA serves as a cellulosomal scaffoldin-like protein for
      several R. flavefaciens enzymes. The data are supported by the direct interaction
      of a recombinant ScaA cohesin with an expressed dockerin-containing enzyme
      construct from the same bacterium. The evidence also demonstrates that the ScaA
      dockerin binds to a specialized cohesin(s) on ScaB, suggesting that ScaB may act
      as an anchoring protein, linked either directly or indirectly to the bacterial
      cell surface. This study is the first direct demonstration in a cellulolytic
      rumen bacterium of a cellulosome system, mediated by distinctive cohesin-dockerin
      interactions.

PMID- 11222593
TI  - Catalytic and molecular properties of the quinohemoprotein tetrahydrofurfuryl
      alcohol dehydrogenase from Ralstonia eutropha strain Bo.
AB  - The quinohemoprotein tetrahydrofurfuryl alcohol dehydrogenase (THFA-DH) from
      Ralstonia eutropha strain Bo was investigated for its catalytic properties. The
      apparent k(cat)/K(m) and K(i) values for several substrates were determined using
      ferricyanide as an artificial electron acceptor. The highest catalytic efficiency
      was obtained with n-pentanol exhibiting a k(cat)/K(m) value of 788 x 10(4) M(-1)
      s(-1). The enzyme showed substrate inhibition kinetics for most of the alcohols
      and aldehydes investigated. A stereoselective oxidation of chiral alcohols with a
      varying enantiomeric preference was observed. Initial rate studies using ethanol
      and acetaldehyde as substrates revealed that a ping-pong mechanism can be assumed
      for in vitro catalysis of THFA-DH. The gene encoding THFA-DH from R. eutropha
      strain Bo (tfaA) has been cloned and sequenced. The derived amino acid sequence
      showed an identity of up to 67% to the sequence of various quinoprotein and
      quinohemoprotein dehydrogenases. A comparison of the deduced sequence with the N
      terminal amino acid sequence previously determined by Edman degradation analysis
      suggested the presence of a signal sequence of 27 residues. The primary structure
      of TfaA indicated that the protein has a tertiary structure quite similar to
      those of other quinoprotein dehydrogenases.

PMID- 11222595
TI  - Effects of ribosomes and intracellular solutes on activities and stabilities of
      elongation factor 2 proteins from psychrotolerant and thermophilic methanogens.
AB  - Low-temperature-adapted archaea are abundant in the environment, yet little is
      known about the thermal adaptation of their proteins. We have previously compared
      elongation factor 2 (EF-2) proteins from Antarctic (Methanococcoides burtonii)
      and thermophilic (Methanosarcina thermophila) methanogens and found that the M.
      burtonii EF-2 had greater intrinsic activity at low temperatures and lower
      thermal stability at high temperatures (T. Thomas and R. Cavicchioli, J.
      Bacteriol. 182:1328-1332, 2000). While the gross thermal properties correlated
      with growth temperature, the activity and stability profiles of the EF-2 proteins
      did not precisely match the optimal growth temperature of each organism. This
      indicated that intracellular components may affect the thermal characteristics of
      the EF-2 proteins, and in this study we examined the effects of ribosomes and
      intracellular solutes. At a high growth temperature the thermophile produced high
      levels of potassium glutamate, which, when assayed in vitro with EF-2, retarded
      thermal unfolding and increased catalytic efficiency. In contrast, for the
      Antarctic methanogen adaptation to growth at a low temperature did not involve
      the accumulation of stabilizing organic solutes but appeared to result from an
      increased affinity of EF-2 for GTP and high levels of EF-2 in the cell relative
      to its low growth rate. Furthermore, ribosomes greatly stimulated GTPase activity
      and moderately stabilized both EF-2 proteins. These findings illustrate the
      different physiological strategies that have evolved in two phylogenetically
      related but thermally distinct methanogens to enable EF-2 to function
      satisfactorily.

PMID- 11222596
TI  - Identification of an Actinobacillus pleuropneumoniae consensus promoter
      structure.
AB  - Actinobacillus pleuropneumoniae promoter-containing clones were isolated from a
      genomic DNA library constructed in our lVET promoter trap vector pTF86. The
      promoter-containing clones were identified by their ability to drive expression
      of the promoterless luxAB genes of Vibrio harveyi. The degree of expression was
      quantifiable, and only high-expression or "hot" promoters were used for this
      study. Nine clones were sequenced, and their transcriptional start sites were
      determined by primer extension. The sequences upstream of the start site were
      aligned, and a consensus promoter structure for A. pleuropneumoniae was
      identified. The consensus promoter sequence for A. pleuropneumoniae was found to
      be TATAAT and TTG/AAA, centered approximately 10 and 35 bp upstream of the
      transcriptional start site, respectively. A comparison of the A. pleuropneumoniae
      consensus with other prokaryotic consensus promoters showed that the A.
      pleuropneumoniae consensus promoter is similar to that found in other eubacteria
      in terms of sequence, with an identical -10 element and a similar but truncated 
      35 element. However, the A. pleuropneumoniae consensus promoter is unique in the
      spacing between the -10 and -35 elements. The promoter spacing was analyzed by
      site-directed mutagenesis, which demonstrated that optimal spacing for an A.
      pleuropneumoniae promoter is shorter than the spacing identified for Escherichia
      coli and Bacillus subtilis promoters.

PMID- 11222594
TI  - Essential thioredoxin-dependent peroxiredoxin system from Helicobacter pylori:
      genetic and kinetic characterization.
AB  - Helicobacter pylori, an oxygen-sensitive microaerophile, contains an alkyl
      hydroperoxide reductase homologue (AhpC, HP1563) that is more closely related to
      2-Cys peroxiredoxins of higher organisms than to most other eubacterial AhpC
      proteins. Allelic replacement mutagenesis revealed ahpC to be essential,
      suggesting a critical role for AhpC in defending H. pylori against oxygen
      toxicity. Characterization of the ahpC promoter region divulged two putative
      regulatory elements and identified the transcription initiation site, which was
      mapped to 96 and 94 bp upstream of the initiation codon. No homologue of ahpF,
      which encodes the dedicated AhpC reductase in most eubacteria, was found in the
      H. pylori genome. Instead, homologues of Escherichia coli thioredoxin (Trx)
      reductase (TrxR, HP0825) and Trx (Trx1, HP0824) formed a reductase system for H.
      pylori AhpC. A second Trx homologue (Trx2, HP1458) was identified but was
      incapable of AhpC reduction, although Trx2 exhibited disulfide reductase activity
      with other substrates [insulin and 5,5'-dithiobis(2-nitrobenzoic acid)]. AhpC
      interactions with each substrate, Trx1 and hydroperoxide, were bimolecular and
      nonsaturable (infinite V(max) and K(m) values) but rapid enough (at 1 x 10(5) to
      2 x 10(5) M(-1) s(-1)) to suggest an important role for AhpC in cellular peroxide
      metabolism. AhpC also exhibited a wide specificity for hydroperoxide substrates,
      which, taken together with the above results, suggests a minimal binding site for
      hydroperoxides composed of little more than the cysteinyl (Cys49) active site. H.
      pylori AhpC was not reduced by Salmonella typhimurium AhpF and was slightly more
      active with E. coli TrxR and Trx1 than was S. typhimurium AhpC, demonstrating the
      specialized catalytic properties of this peroxiredoxin.

PMID- 11222597
TI  - Gene expression in Pseudomonas aeruginosa: evidence of iron override effects on
      quorum sensing and biofilm-specific gene regulation.
AB  - Prior studies established that the Pseudomonas aeruginosa oxidative stress
      response is influenced by iron availability, whereas more recent evidence
      demonstrated that it was also controlled by quorum sensing (QS) regulatory
      circuitry. In the present study, sodA (encoding manganese-cofactored superoxide
      dismutase [Mn-SOD]) and Mn-SOD were used as a reporter gene and endogenous
      reporter enzyme, respectively, to reexamine control mechanisms that govern the
      oxidative stress response and to better understand how QS and a nutrient stress
      response interact or overlap in this bacterium. In cells grown in Trypticase soy
      broth (TSB), Mn-SOD was found in wild-type stationary-phase planktonic cells but
      not in a lasI or lasR mutant. However, Mn-SOD activity was completely suppressed
      in the wild-type strain when TSB was supplemented with iron. Reporter gene
      studies indicated that sodA transcription could be variably induced in iron
      starved cells of all three strains, depending on growth stage. Iron starvation
      induction of sodA was greatest in the wild-type strain and least in the lasR
      mutant and was maximal in stationary-phase cells. Reporter experiments in the
      wild-type strain showed increased lasI::lacZ transcription in response to iron
      limitation, whereas the expression level in the las mutants was minimal and iron
      starvation induction of lasI::lacZ did not occur. Studies comparing Mn-SOD
      activity in P. aeruginosa biofilms and planktonic cultures were also initiated.
      In wild-type biofilms, Mn-SOD was not detected until after 6 days, although in
      iron-limited wild-type biofilms Mn-SOD was detected within the initial 24 h of
      biofilm establishment and formation. Unlike planktonic bacteria, Mn-SOD was
      constitutive in the lasI and lasR mutant biofilms but could be suppressed if the
      growth medium was amended with 25 microM ferric chloride. This study demonstrated
      that (i) the nutritional status of the cell must be taken into account when one
      is evaluating QS-based gene expression; (ii) in the biofilm mode of growth, QS
      may also have negative regulatory functions; (iii) QS-based gene regulation
      models based on studies with planktonic cells must be modified in order to
      explain biofilm gene expression behavior; and (iv) gene expression in biofilms is
      dynamic.

PMID- 11222598
TI  - Hfq is necessary for regulation by the untranslated RNA DsrA.
AB  - DsrA is an 85-nucleotide, untranslated RNA that has multiple regulatory
      activities at 30 degrees C. These activities include the translational regulation
      of RpoS and H-NS, global transcriptional regulators in Escherichia coli. Hfq is
      an E. coli protein necessary for the in vitro and in vivo replication of the RNA
      phage Qbeta. Hfq also plays a role in the degradation of numerous RNA
      transcripts. Here we show that an hfq mutant strain is defective for DsrA
      mediated regulation of both rpoS and hns. The defect in rpoS expression can be
      partially overcome by overexpression of DsrA. Hfq does not regulate the
      transcription of DsrA, and DsrA does not alter the accumulation of Hfq. However,
      in an hfq mutant, chromosome-expressed DsrA was unstable (half-life of 1 min) and
      truncated at the 3' end. When expressed from a multicopy plasmid, DsrA was stable
      in both wild-type and hfq mutant strains, but it had only partial activity in the
      hfq mutant strain. Purified Hfq binds DsrA in vitro. These results suggest that
      Hfq acts as a protein cofactor for the regulatory activities of DsrA by either
      altering the structure of DsrA or forming an active RNA-protein complex.

PMID- 11222599
TI  - SecG function and phospholipid metabolism in Escherichia coli.
AB  - SecG is an auxiliary protein in the Sec-dependent protein export pathway of
      Escherichia coli. Although the precise function of SecG is unknown, it stimulates
      translocation activity and has been postulated to enhance the membrane insertion
      deinsertion cycle of SecA. Deletion of secG was initially reported to result in a
      severe export defect and cold sensitivity. Later results demonstrated that both
      of these phenotypes were strain dependent, and it was proposed that an additional
      mutation was required for manifestation of the cold-sensitive phenotype. The
      results presented here demonstrate that the cold-sensitive secG deletion strain
      also contains a mutation in glpR that causes constitutive expression of the glp
      regulon. Introduction of both the glpR mutation and the secG deletion into a wild
      type strain background produced a cold-sensitive phenotype, confirming the
      hypothesis that a second mutation (glpR) contributes to the cold-sensitive
      phenotype of secG deletion strains. It was speculated that the glpR mutation
      causes an intracellular depletion of glycerol-3-phosphate due to constitutive
      synthesis of GlpD and subsequent channeling of glycerol-3-phosphate into
      metabolic pathways. In support of this hypothesis, it was demonstrated that
      addition of glycerol-3-phosphate to the growth medium ameliorated the cold
      sensitivity, as did introduction of a glpD mutation. This depletion of glycerol-3
      phosphate is predicted to limit phospholipid biosynthesis, causing an imbalance
      in the levels of membrane phospholipids. It is hypothesized that this state of
      phospholipid imbalance imparts a dependence on SecG for proper function or
      stabilization of the translocation apparatus.

PMID- 11222600
TI  - Mobile cytochrome c2 and membrane-anchored cytochrome cy are both efficient
      electron donors to the cbb3- and aa3-type cytochrome c oxidases during
      respiratory growth of Rhodobacter sphaeroides.
AB  - We have recently established that the facultative phototrophic bacterium
      Rhodobacter sphaeroides, like the closely related Rhodobacter capsulatus species,
      contains both the previously characterized mobile electron carrier cytochrome c2
      (cyt c2) and the more recently discovered membrane-anchored cyt cy. However, R.
      sphaeroides cyt cy, unlike that of R. capsulatus, is unable to function as an
      efficient electron carrier between the photochemical reaction center and the cyt
      bc1 complex during photosynthetic growth. Nonetheless, R. sphaeroides cyt cy can
      act at least in R. capsulatus as an electron carrier between the cyt bc1 complex
      and the cbb3-type cyt c oxidase (cbb3-Cox) to support respiratory growth. Since
      R. sphaeroides harbors both a cbb3-Cox and an aa3-type cyt c oxidase (aa3-Cox),
      we examined whether R. sphaeroides cyt cy can act as an electron carrier to
      either or both of these respiratory terminal oxidases. R. sphaeroides mutants
      which lacked either cyt c2 or cyt cy and either the aa3-Cox or the cbb3-Cox were
      obtained. These double mutants contained linear respiratory electron transport
      pathways between the cyt bc1 complex and the cyt c oxidases. They were
      characterized with respect to growth phenotypes, contents of a-, b-, and c-type
      cytochromes, cyt c oxidase activities, and kinetics of electron transfer mediated
      by cyt c2 or cyt cy. The findings demonstrated that both cyt c2 and cyt cy are
      able to carry electrons efficiently from the cyt bc1 complex to either the cbb3
      Cox or the aa3-Cox. Thus, no dedicated electron carrier for either of the cyt c
      oxidases is present in R. sphaeroides. However, under semiaerobic growth
      conditions, a larger portion of the electron flow out of the cyt bc1 complex
      appears to be mediated via the cyt c2-to-cbb3-Cox and cyt cy-to-cbb3-Cox
      subbranches. The presence of multiple electron carriers and cyt c oxidases with
      different properties that can operate concurrently reveals that the respiratory
      electron transport pathways of R. sphaeroides are more complex than those of R.
      capsulatus.

PMID- 11222601
TI  - Identification of the varR gene as a transcriptional regulator of virginiamycin S
      resistance in Streptomyces virginiae.
AB  - A gene designated varR (for virginiae antibiotic resistance regulator) was
      identified in Streptomyces virginiae 89 bp downstream of a varS gene encoding a
      virginiamycin S (VS)-specific transporter. The deduced varR product showed high
      homology to repressors of the TetR family with a conserved helix-turn-helix DNA
      binding motif. Purified recombinant VarR protein was present as a dimer in vitro
      and showed clear DNA binding activity toward the varS promoter region. This
      binding was abolished by the presence of VS, suggesting that VarR regulates
      transcription of varS in a VS-dependent manner. Northern blot analysis revealed
      that varR was cotranscribed with upstream varS as a 2.4-kb transcript and that VS
      acted as an inducer of bicistronic transcription. Deletion analysis of the varS
      promoter region clarified two adjacent VarR binding sites in the varS promoter.

PMID- 11222602
TI  - Alternative translation initiation produces a short form of a spore coat protein
      in Bacillus subtilis.
AB  - During endospore formation in Bacillus subtilis, over two dozen polypeptides are
      localized to the developing spore and coordinately assembled into a thick
      multilayered structure called the spore coat. Assembly of the coat is initiated
      by the expression of morphogenetic proteins SpoIVA, CotE, and SpoVID. These
      morphogenetic proteins appear to guide the assembly of other proteins into the
      spore coat. For example, SpoVID forms a complex with the SafA protein, which is
      incorporated into the coat during the early stages of development. At least two
      forms of SafA are found in the mature spore coat: a full-length form and a
      shorter form (SafA-C(30)) that begins with a methionine encoded by codon 164 of
      safA. In this study, we present evidence that the expression of SafA-C(30) arises
      from translation initiation at codon 164. We found only a single transcript
      driving expression of SafA. A stop codon engineered just upstream of a predicted
      ribosome-binding site near codon M164 abolished formation of full-length SafA,
      but not SafA-C(30). The same effect was observed with an alanine substitution at
      codon 1 of SafA. Accumulation of SafA-C(30) was blocked by substitution of an
      alanine codon at codon 164, but not by a substitution at a nearby methionine at
      codon 161. We found that overproduction of SafA-C(30) interfered with the
      activation of late mother cell-specific transcription and caused a strong
      sporulation block.

PMID- 11222603
TI  - Programmed cell death in Escherichia coli: some antibiotics can trigger mazEF
      lethality.
AB  - The discovery of toxin-antitoxin gene pairs (also called addiction modules) on
      extrachromosomal elements of Escherichia coli, and particularly the discovery of
      homologous modules on the bacterial chromosome, suggest that a potential for
      programmed cell death may be inherent in bacterial cultures. We have reported on
      the E. coli mazEF system, a regulatable addiction module located on the bacterial
      chromosome. MazF is a stable toxin and MazE is a labile antitoxin. Here we show
      that cell death mediated by the E. coli mazEF module can be triggered by several
      antibiotics (rifampicin, chloramphenicol, and spectinomycin) that are general
      inhibitors of transcription and/or translation. These antibiotics inhibit the
      continuous expression of the labile antitoxin MazE, and as a result, the stable
      toxin MazF causes cell death. Our results have implications for the possible
      mode(s) of action of this group of antibiotics.

PMID- 11222604
TI  - Postsegregational killing mediated by the P1 phage "addiction module" phd-doc
      requires the Escherichia coli programmed cell death system mazEF.
AB  - "Addiction modules" consist of two genes; the product of the second is long lived
      and toxic, while the product of the first is short lived and antagonizes the
      lethal action of the toxin. The extrachromosomal addiction module phd-doc,
      located on the P1 prophage, is responsible for the postsegregational killing
      effect (death of plasmid-free cells). The Escherichia coli chromosomal addiction
      module analogue, mazEF, is responsible for the induction of programmed cell
      death. Here we show that the postsegregational killing mediated by the P1 phd-doc
      module depends on the presence of the E. coli mazEF system. In addition, we
      demonstrate that under conditions of postsegregational killing, mediated by phd
      doc, protein synthesis of E. coli is inhibited. Based on our findings, we suggest
      the existence of a coupling between the phd-doc and mazEF systems.

PMID- 11222605
TI  - D-alanylation of lipoteichoic acid: role of the D-alanyl carrier protein in
      acylation.
AB  - The D-alanylation of membrane-associated lipoteichoic acid (LTA) in gram-positive
      organisms requires the D-alanine-D-alanyl carrier protein ligase (AMP) (Dcl) and
      the D-alanyl carrier protein (Dcp). The dlt operon encoding these proteins (dltA
      and dltC) also includes dltB and dltD. dltB encodes a putative transport system,
      while dltD encodes a protein which facilitates the binding of Dcp and Dcl for
      ligation with D-alanine and has thioesterase activity for mischarged D-alanyl
      acyl carrier proteins (ACPs). In previous results it was shown that D-alanyl-Dcp
      donates its ester residue to membrane-associated LTA (M. P. Heaton and F. C.
      Neuhaus, J. Bacteriol. 176: 681-690, 1994). However, all efforts to identify an
      enzyme which catalyzes this D-alanylation process were unsuccessful. It was
      discovered that incubation of D-alanyl-Dcp in the presence of LTA resulted in the
      time-dependent hydrolysis of this D-alanyl thioester. D-Alanyl-ACP in the
      presence of LTA was not hydrolyzed. When Dcp was incubated with membrane
      associated D-alanyl LTA, a time and concentration-dependent formation of D-alanyl
      Dcp was found. The addition of NaCl to this reaction inhibited the formation of D
      alanyl-Dcp and stimulated the hydrolysis of D-alanyl-Dcp. Since these reactions
      are specific for the carrier protein (Dcp), it is suggested that Dcp has a unique
      binding site which interacts with the poly(Gro-P) moiety of LTA. It is this
      specific interaction that provides the functional specificity for the D
      alanylation process. The reversibility of this process provides a mechanism for
      the transacylation of the D-alanyl ester residues between LTA and wall teichoic
      acid.

PMID- 11222606
TI  - Regulatory architecture of the iron-regulated fepD-ybdA bidirectional promoter
      region in Escherichia coli.
AB  - The overlapping and opposing promoter elements for the Escherichia coli fepDGC
      operon and the ybdA gene (encoding a 43-kDa cytoplasmic membrane protein) within
      the enterobactin gene cluster were investigated by measuring the effects of site
      specific mutations on transcript levels and on expression of reporter genes in a
      bidirectional transcriptional fusion vector. Primary promoter structures for the
      opposing transcripts overlapped extensively such that their -10 sequences were
      almost directly opposed on the two strands of the DNA helix and their +1
      transcription start sites were only 23 bp apart. Relative to the E. coli
      consensus sequence, both promoters were poorly conserved at the -35 position and
      mutations which strengthened the -35 element of either promoter significantly
      enhanced its transcription, decreased that of the opposing promoter, and
      dramatically altered iron-mediated regulation of expression. Both the fepD and
      ybdA primary promoters were shown to require a 5'-TGn-3' upstream extension of
      their -10 elements for optimal activities. Secondary promoters were identified
      for both fepD and ybdA, and their contributions to the overall expression levels
      were evaluated in these dual expression vector constructs. The data provided
      strong evidence that the architecture of the regulatory elements within the
      overlapping fepD and ybdA promoters is configured such that there is a direct
      competition for binding RNA polymerase and that the expression levels at these
      promoters are influenced not only by the activity of the opposing promoters but
      also by additional promoter sequence elements and perhaps accessory regulatory
      factors. Iron-mediated regulation of these promoters through the repressor
      protein Fur is a consequence of the relative promoter strengths and the position
      of an operator site that consists of two overlapping Fur-binding sequences in
      this compact regulatory region.

PMID- 11222608
TI  - Role for a phage promoter in Shiga toxin 2 expression from a pathogenic
      Escherichia coli strain.
AB  - Shiga toxins (Stxs), encoded by the stxA and stxB genes, are important
      contributors to the virulence of Escherichia coli O157:H7 and other Stx-producing
      E. coli (STEC) strains. The stxA and stxB genes in STEC strains are located on
      the genomes of resident prophages of the lambda family immediately downstream of
      the phage late promoters (p(R')). The phage-encoded Q proteins modify RNA
      polymerase initiating transcription at the cognate p(R') promoter which creates
      transcription complexes that transcend a transcription terminator immediately
      downstream of p(R') as well as terminator kilobases distal to p(R'). To test if
      this Q-directed processive transcription plays a role in stx(2)AB expression, we
      constructed a mutant prophage in an O157:H7 clinical isolate from which p(R') and
      part of Q were deleted but which has an intact pStx, the previously described
      stx(2)AB-associated promoter. We report that production of significant levels of
      Stx2 in this O157:H7 isolate depends on the p(R') promoter. Since transcription
      initiating at p(R') ultimately requires activation of the phage lytic cascade,
      expression of stx(2)AB in STEC depends primarily on prophage induction. By
      showing this central role for the prophage in stx(2)AB expression, our findings
      contradict the prevailing assumption that phages serve merely as agents for
      virulence gene transfer.

PMID- 11222607
TI  - MeaA, a putative coenzyme B12-dependent mutase, provides methylmalonyl coenzyme A
      for monensin biosynthesis in Streptomyces cinnamonensis.
AB  - The ratio of the major monensin analogs produced by Streptomyces cinnamonensis is
      dependent upon the relative levels of the biosynthetic precursors methylmalonyl
      coenzyme A (CoA) (monensin A and monensin B) and ethylmalonyl-CoA (monensin A).
      The meaA gene of this organism was cloned and sequenced and was shown to encode a
      putative 74-kDa protein with significant amino acid sequence identity to
      methylmalonyl-CoA mutase (MCM) (40%) and isobutyryl-CoA mutase (ICM) large
      subunit (36%) and small subunit (52%) from the same organism. The predicted C
      terminus of MeaA contains structural features highly conserved in all coenzyme
      B12-dependent mutases. Plasmid-based expression of meaA from the ermE* promoter
      in the S. cinnamonensis C730.1 strain resulted in a decreased ratio of monensin A
      to monensin B, from 1:1 to 1:3. Conversely, this ratio increased to 4:1 in a meaA
      mutant, S. cinnamonensis WM2 (generated from the C730.1 strain by insertional
      inactivation of meaA by using the erythromycin resistance gene). In both of these
      experiments, the overall monensin titers were not significantly affected.
      Monensin titers, however, did decrease over 90% in an S. cinnamonensis WD2 strain
      (an icm meaA mutant). Monensin titers in the WD2 strain were restored to at least
      wild-type levels by plasmid-based expression of the meaA gene or the
      Amycolatopsis mediterranei mutAB genes (encoding MCM). In contrast, growth of the
      WD2 strain in the presence of 0.8 M valine led only to a partial restoration
      (<25%) of monensin titers. These results demonstrate that the meaA gene product
      is significantly involved in methylmalonyl-CoA production in S. cinnamonensis and
      that under the tested conditions the presence of both MeaA and ICM is crucial for
      monensin production in the WD2 strain. These results also indicate that valine
      degradation, implicated in providing methylmalonyl-CoA precursors for many
      polyketide biosynthetic processes, does not do so to a significant degree for
      monensin biosynthesis in the WD2 mutant.

PMID- 11222609
TI  - Occurrence of transsulfuration in synthesis of L-homocysteine in an extremely
      thermophilic bacterium, Thermus thermophilus HB8.
AB  - A cell extract of an extremely thermophilic bacterium, Thermus thermophilus HB8,
      cultured in a synthetic medium catalyzed cystathionine gamma-synthesis with O
      acetyl-L-homoserine and L-cysteine as substrates but not beta-synthesis with DL
      homocysteine and L-serine (or O-acetyl-L-serine). The amounts of synthesized
      enzymes metabolizing sulfur-containing amino acids were estimated by determining
      their catalytic activities in cell extracts. The syntheses of cystathionine beta
      lyase (EC 4.4.1.8) and O-acetyl-L-serine sulfhydrylase (EC 4.2.99.8) were
      markedly repressed by L-methionine supplemented to the medium. L-Cysteine and
      glutathione, both at 0.5 mM, added to the medium as the sole sulfur source
      repressed the synthesis of O-acetylserine sulfhydrylase by 55 and 73%,
      respectively, confirming that this enzyme functions as a cysteine synthase.
      Methionine employed at 1 to 5 mM in the same way derepressed the synthesis of O
      acetylserine sulfhydrylase 2.1- to 2.5-fold. A method for assaying a low
      concentration of sulfide (0.01 to 0.05 mM) liberated from homocysteine by
      determining cysteine synthesized with it in the presence of excess amounts of O
      acetylserine and a purified preparation of the sulfhydrylase was established. The
      extract of cells catalyzed the homocysteine gamma-lyase reaction, with a specific
      activity of 5 to 7 nmol/min/mg of protein, but not the methionine gamma-lyase
      reaction. These results suggested that cysteine was also synthesized under the
      conditions employed by the catalysis of O-acetylserine sulfhydrylase using sulfur
      of homocysteine derived from methionine. Methionine inhibited O-acetylserine
      sulfhydrylase markedly. The effects of sulfur sources added to the medium on the
      synthesis of O-acetylhomoserine sulfhydrylase and the inhibition of the enzyme
      activity by methionine were mostly understood by assuming that the organism has
      two proteins having O-acetylhomoserine sulfhydrylase activity, one of which is
      cystathionine gamma-synthase. Although it has been reported that homocysteine is
      directly synthesized in T. thermophilus HB27 by the catalysis of O
      acetylhomoserine sulfhydrylase on the basis of genetic studies (T. Kosuge, D.
      Gao, and T. Hoshino, J. Biosci. Bioeng. 90:271-279, 2000), the results obtained
      in this study for the behaviors of related enzymes indicate that sulfur is first
      incorporated into cysteine and then transferred to homocysteine via cystathionine
      in T. thermophilus HB8.

PMID- 11222610
TI  - Functional characterization of a novel xylanase from a corn strain of Erwinia
      chrysanthemi.
AB  - A beta-1,4-xylan hydrolase (xylanase A) produced by Erwinia chrysanthemi D1
      isolated from corn was analyzed with respect to its secondary structure and
      enzymatic function. The pH and temperature optima for the enzyme were found to be
      pH 6.0 and 35 degrees C, with a secondary structure under those conditions that
      consists of approximately 10 to 15% alpha-helices. The enzyme was still active at
      temperatures higher than 40 degrees C and at pHs of up to 9.0. The loss of
      enzymatic activity at temperatures above 45 degrees C was accompanied by
      significant loss of secondary structure. The enzyme was most active on xylan
      substrates with low ratios of xylose to 4-O-methyl-D-glucuronic acid and appears
      to require two 4-O-methyl-D-glucuronic acid residues for substrate recognition
      and/or cleavage of a beta-1,4-xylosidic bond. The enzyme hydrolyzed sweetgum
      xylan, generating products with a 4-O-methyl-glucuronic acid-substituted xylose
      residue one position from the nonreducing terminus of the oligoxyloside product.
      No internal cleavages of the xylan backbone between substituted xylose residues
      were observed, giving the enzyme a unique mode of action in the hydrolysis
      compared to all other xylanases that have been described. Given the size of the
      oligoxyloside products generated by the enzyme during depolymerization of xylan
      substrates, the function of the enzyme may be to render substrate available for
      other depolymerizing enzymes instead of producing oligoxylosides for cellular
      metabolism and may serve to produce elicitors during the initiation of the
      infectious process.

PMID- 11222611
TI  - Mobilization function of the pBHR1 plasmid, a derivative of the broad-host-range
      plasmid pBBR1.
AB  - The pBHR1 plasmid is a derivative of the small (2.6-kb), mobilizable broad-host
      range plasmid pBBR1, which was isolated from the gram-negative bacterium
      Bordetella bronchiseptica (R. Antoine and C. Locht, Mol. Microbiol. 6:1785-1799,
      1992). Plasmid pBBR1 consists of two functional cassettes and presents sequence
      similarities with the transfer origins of several plasmids and mobilizable
      transposons from gram-positive bacteria. We show that the Mob protein
      specifically recognizes a 52-bp sequence which contains, in addition to the
      transfer origin, the promoter of the mob gene. We demonstrate that this gene is
      autoregulated. The binding of the Mob protein to the 52-bp sequence could thus
      allow the formation of a protein-DNA complex with a double function: relaxosome
      formation and mob gene regulation. We show that the Mob protein is a relaxase,
      and we located the nic site position in vitro. After sequence alignment, the
      position of the nic site of pBBR1 corresponds with those of the nick sites of the
      Bacteroides mobilizable transposon Tn4555 and the streptococcal plasmid pMV158.
      The oriT of the latter is characteristic of a family of mobilizable plasmids that
      are found in gram-positive bacteria and that replicate by the rolling-circle
      mechanism. Plasmid pBBR1 thus appears to be a new member of this group, even
      though it resides in gram-negative bacteria and does not replicate via a rolling
      circle mechanism. In addition, we identified two amino acids of the Mob protein
      necessary for its activity, and we discuss their involvement in the mobilization
      mechanism.

PMID- 11222612
TI  - Involvement of domain 3 in oligomerization by the protective antigen moiety of
      anthrax toxin.
AB  - Protective antigen (PA), a component of anthrax toxin, binds receptors on
      mammalian cells and is activated by a cell surface protease. The resulting active
      fragment, PA(63), forms ring-shaped heptamers, binds the enzymic moieties of the
      toxin, and translocates them to the cytosol. Of the four crystallographic domains
      of PA, domain 1 has been implicated in binding the enzymic moieties; domain 2 is
      involved in membrane insertion and oligomerization; and domain 4 binds receptor.
      To determine the function of domain 3, we developed a screen that allowed us to
      isolate random mutations that cause defects in the activity of PA. We identified
      several mutations in domain 3 that affect monomer-monomer interactions in the
      PA(63) heptamer, indicating that this may be the primary function of this domain.

PMID- 11222613
TI  - Phase-variable expression of an operon encoding extracellular alkaline protease,
      a serine protease homolog, and lipase in Pseudomonas brassicacearum.
AB  - The rhizobacterium Pseudomonas brassicacearum forms phenotypic variants which do
      not show extracellular protease and lipase activity. The operon encoding these
      enzymes, a serine protease homolog, and a type I secretion machinery was
      characterized. Transcriptional lacZ gene fusions revealed that the expression of
      the operon is under the control of phase variation.

PMID- 11222614
TI  - Novel lysophospholipase A secreted by Legionella pneumophila.
AB  - We show that Legionella pneumophila possesses lysophospholipase A activity, which
      releases fatty acids from lysophosphatidylcholine. The NH2-terminal sequence of
      the enzyme contained FGDSLS, corresponding to a catalytic domain in a recently
      described group of lipolytic enzymes. Culture supernatants of a L. pneumophila
      pilD mutant lost the ability to cleave lysophosphatidylcholine.

PMID- 11222615
TI  - snr-1 gene is required for nitrate reduction in Pseudomonas aeruginosa PAO1.
AB  - Pseudomonas aeruginosa is able to use nitrate for both assimilation and anaerobic
      respiration. One set of genes, designated snr (for "shared nitrate reduction"),
      have been recently cloned and partially characterized. In this study, we
      demonstrate that the snr-1 gene encodes a predicted 52.5-kDa protein that is 82%
      similar to a unique cytochrome c of Desulfomonile tiedjei DCB-1. Importantly, the
      Snr-1 protein sequence of P. aeruginosa differed from that of the cytochrome c of
      D. tiedjei primarily in the first 25 amino acids, which are required for membrane
      attachment in D. tiedjei. In P. aeruginosa, the Snr-1 protein hydropathy profile
      indicates that it is a soluble protein. An isogenic snr-1::Gm insertional mutant
      was unable to grow aerobically with nitrate as a sole nitrogen source or
      anaerobically with nitrate as an electron acceptor. Complementation of the snr
      1::Gm mutant with the snr-1 gene restored the wild-type phenotypes.
      Interestingly, anaerobic growth rates were significantly higher in the snr-1
      mutant harboring a multicopy plasmid containing snr-1. In contrast, aerobic
      growth rates of the restored mutant using nitrate as the sole nitrogen source
      were similar to those of the wild type. Transcriptional lacZ fusions demonstrated
      that snr-1 was not regulated by molybdate, oxygen, or nitrate.

PMID- 11222616
TI  - Identification of specific residues in colicin E1 involved in immunity protein
      recognition.
AB  - The basis of specificity between pore-forming colicins and immunity proteins was
      explored by interchanging residues between colicins E1 (ColE1) and 10 (Col10) and
      testing for altered recognition by their respective immunity proteins, Imm and
      Cti. A total of 34 divergent residues in the pore-forming domain of ColE1 between
      residues 419 and 501, a region previously shown to contain the specificity
      determinants for Imm, were mutagenized to the corresponding Col10 sequences. The
      residue changes most effective in converting ColE1 to the Col10 phenotype are
      residue 448 at the N terminus of helix VI and residues 470, 472, and 474 at the C
      terminus of helix VII. Mutagenesis of helix VI residues 416 to 419 in Col10 to
      the corresponding ColE1 sequence resulted in increased recognition by Imm and
      loss of recognition by Cti.

PMID- 11222617
TI  - Construction and characterization of mutations at codon 751 of the Escherichia
      coli gyrB gene that confer resistance to the antimicrobial peptide microcin B17
      and alter the activity of DNA gyrase.
AB  - Microcin B17 is a peptide antibiotic that inhibits DNA replication in Escherichia
      coli by targeting DNA gyrase. Previously, two independently isolated microcin B17
      resistant mutants were shown to harbor the same gyrB point mutation that results
      in the replacement of tryptophan 751 by arginine in the GyrB polypeptide. We used
      site-directed mutagenesis to construct mutants in which tryptophan 751 was
      deleted or replaced by other amino acids. These mutants exhibit altered DNA
      gyrase activity and different levels of resistance to microcin B17.

PMID- 11222618
TI  - Symbiotic plasmid rearrangement in Rhizobium leguminosarum bv. viciae VF39SM.
AB  - A rearrangement between the symbiotic plasmid (pRleVF39d) and a nonsymbiotic
      plasmid (pRleVF39b) in Rhizobium leguminosarum bv. viciae VF39 was observed. The
      rearranged derivative showed the same plasmid profile as its parent strain, but
      hybridization to nod, fix, and nif genes indicated that most of the symbiotic
      genes were now present on a plasmid corresponding in size to pRleVF39b instead of
      pRleVF39d. On the other hand, some DNA fragments originating from pRleVF39b now
      hybridized to the plasmid band at the position of pRleVF39d. These results
      suggest that a reciprocal but unequal DNA exchange between the two plasmids had
      occurred.

PMID- 11222619
TI  - Genes involved in copper homeostasis in Escherichia coli.
AB  - Recently, genes for two copper-responsive regulatory systems were identified in
      the Escherichia coli chromosome. In this report, data are presented that support
      a hypothesis that the putative multicopper oxidase CueO and the transenvelope
      transporter CusCFBA are involved in copper tolerance in E. coli.

PMID- 11222620
TI  - DnaD protein of Bacillus subtilis interacts with DnaA, the initiator protein of
      replication.
AB  - The yeast two-hybrid assay revealed that Bacillus subtilis DnaD, a possible
      component of the primosome and required for replication initiation, interacted
      with DnaA and DnaD itself. The mutant DnaD23 was incapable of interacting with
      DnaA but retained interaction with the wild-type DnaD. These results suggest that
      interaction between DnaD and DnaA is important for replication initiation.

PMID- 11222621
TI  - Analysis of promoters recognized by PvdS, an extracytoplasmic-function sigma
      factor protein from Pseudomonas aeruginosa.
AB  - The alternative sigma factor PvdS is required by Pseudomonas aeruginosa for
      initiation of transcription from pyoverdine (pvd) promoters. Two divergent PvdS
      dependent promoters (pvdE and pvdF) were characterized by deletion analysis, and
      the minimal promoter region for each included a sequence element, the iron
      starvation (IS) box, that is present in other pvd promoters. Site-directed
      mutagenesis showed that the IS box elements were essential for promoter activity
      in vivo. Band shift assays and in vitro transcription experiments showed that a
      complex of PvdS and core RNA polymerase required the presence of an IS box in
      order to bind to and initiate transcription from pvd promoters. These results
      indicate that IS box elements participate in sequence-specific recognition by
      PvdS to enable initiation of transcription from pvd promoters and are likely to
      represent a -35 sequence element for this sigma factor.

PMID- 11222622
TI  - Activation of glycogen synthase by insulin in 3T3-L1 adipocytes involves c-Cbl
      associating protein (CAP)-dependent and CAP-independent signaling pathways.
AB  - In adipose and muscle, insulin stimulates glucose uptake and glycogen synthase
      activity. Phosphatidylinositol 3-kinase (PI3K) activation is necessary but not
      sufficient for these metabolic actions of insulin. The insulin-stimulated
      translocation of phospho-c-Cbl to lipid rafts, via its association with CAP,
      comprises a second pathway regulating GLUT4 translocation. In 3T3-L1 adipocytes,
      overexpression of a dominant negative CAP mutant (CAP Delta SH3) completely
      blocked the insulin-stimulated glucose transport and glycogen synthesis but only
      partially inhibited glycogen synthase activation. In contrast, CAP Delta SH3
      expression did not affect glycogen synthase activation by insulin in the absence
      of extracellular glucose. Moreover, CAP Delta SH3 has no effect on the PI3K
      dependent activation of protein phosphatase-1 or phosphorylation of glycogen
      synthase kinase-3. These results indicate blockade of the c-Cbl/CAP pathway
      directly inhibits insulin-stimulated glucose uptake, which results in secondary
      inhibition of glycogen synthase activation and glycogen synthesis.

PMID- 11222625
TI  - Helical structure of the COOH terminus of S3 and its contribution to the gating
      modifier toxin receptor in voltage-gated ion channels.
AB  - The voltage-sensing domains in voltage-gated K(+) channels each contain four
      transmembrane (TM) segments, termed S1 to S4. Previous scanning mutagenesis
      studies suggest that S1 and S2 are amphipathic membrane spanning alpha-helices
      that interface directly with the lipid membrane. In contrast, the secondary
      structure of and/or the environments surrounding S3 and S4 are more complex. For
      S3, although the NH(2)-terminal part displays significant helical character in
      both tryptophan- and alanine-scanning mutagenesis studies, the structure of the
      COOH-terminal portion of this TM is less clear. The COOH terminus of S3 is
      particularly interesting because this is where gating modifier toxins like
      Hanatoxin interact with different voltage-gated ion channels. To further examine
      the secondary structure of the COOH terminus of S3, we lysine-scanned this region
      in the drk1 K(+) channel and examined the mutation-induced changes in channel
      gating and Hanatoxin binding affinity, looking for periodicity characteristic of
      an alpha-helix. Both the mutation-induced perturbation in the toxin-channel
      interaction and in gating support the presence of an alpha-helix of at least 10
      residues in length in the COOH terminus of S3. Together with previous scanning
      mutagenesis studies, these results suggest that, in voltage-gated K(+) channels,
      the entire S3 segment is helical, but that it can be divided into two parts. The
      NH(2)-terminal part of S3 interfaces with both lipid and protein, whereas the
      COOH-terminal part interfaces with water (where Hanatoxin binds) and possibly
      protein. A conserved proline residue is located near the boundary between the two
      parts of S3, arguing for the presence of a kink in this region. Several lines of
      evidence suggest that these structural features of S3 probably exist in all
      voltage-gated ion channels.

PMID- 11222626
TI  - Mechanism of inhibition of cyclic nucleotide-gated channel by protein tyrosine
      kinase probed with genistein.
AB  - Rod cyclic nucleotide-gated (CNG) channels are modulated by changes in tyrosine
      phosphorylation catalyzed by protein tyrosine kinases (PTKs) and phosphatases
      (PTPs). We used genistein, a PTK inhibitor, to probe the interaction between the
      channel and PTKs. Previously, we found that in addition to inhibiting tyrosine
      phosphorylation of the rod CNG channel alpha-subunit (RETalpha), genistein
      triggers a noncatalytic inhibitory interaction between the PTK and the channel.
      These studies suggest that PTKs affects RETalpha channels in two ways: (1) by
      catalyzing phosphorylation of the channel protein, and (2) by allosterically
      regulating channel activation. Here, we study the mechanism of noncatalytic
      inhibition. We find that noncatalytic inhibition follows the same activity
      dependence pattern as catalytic modulation (phosphorylation): the efficacy and
      apparent affinity of genistein inhibition are much higher for closed than for
      fully activated channels. Association rates with the genistein-PTK complex were
      similar for closed and fully activated channels and independent of genistein
      concentration. Dissociation rates were 100 times slower for closed channels,
      which is consistent with a much higher affinity for genistein-PTK. Genistein-PTK
      affects channel gating, but not single channel conductance or the number of
      active channels. By analyzing single channel gating during genistein-PTK
      dissociation, we determined the maximal open probability for normal and genistein
      PTK-bound channels. genistein-PTK decreases open probability by increasing the
      free energy required for opening, making opening dramatically less favorable.
      Ni(2+), which potentiates RETalpha channel gating, partially relieves genistein
      inhibition, possibly by disrupting the association between the genistein-PTK and
      the channel. Studies on chimeric channels containing portions of RETalpha, which
      exhibits genistein inhibition, and the rat olfactory CNG channel alpha-subunit,
      which does not, reveals that a domain containing S6 and flanking regions is the
      crucial for genistein inhibition and may constitute the genistein-PTK binding
      site. Thus, genistein-PTK stabilizes the closed state of the channel by
      interacting with portions of the channel that participate in gating.

PMID- 11222627
TI  - Scam feels the pinch.

PMID- 11222628
TI  - Location of a constriction in the lumen of a transmembrane pore by targeted
      covalent attachment of polymer molecules.
AB  - Few methods exist for obtaining the internal dimensions of transmembrane pores
      for which 3-D structures are lacking or for showing that structures determined by
      crystallography reflect the internal dimensions of pores in lipid bilayers.
      Several approaches, involving polymer penetration and transport, have revealed
      limiting diameters for various pores. But, in general, these approaches do not
      indicate the locations of constrictions in the channel lumen. Here, we combine
      cysteine mutagenesis and chemical modification with sulfhydryl-reactive polymers
      to locate the constriction in the lumen of the staphylococcal alpha-hemolysin
      pore, a model protein of known structure. The rates of reaction of each of four
      polymeric reagents (MePEG-OPSS) of different masses towards individual single
      cysteine mutants, comprising a set with cysteines distributed over the length of
      the lumen of the pore, were determined by macroscopic current recording. The
      rates for the three larger polymers (1.8, 2.5, and 5.0 kD) were normalized with
      respect to the rates of reaction with a 1.0-kD polymer for each of the seven
      positions in the lumen. The rate of reaction of the 5.0-kD polymer dropped
      dramatically at the centrally located Cys-111 residue and positions distal to Cys
      111, whether the reagent was applied from the trans or the cis side of the
      bilayer. This semi-quantitative analysis sufficed to demonstrate that a
      constriction is located at the midpoint of the pore lumen, as predicted by the
      crystal structure, and although the constriction allows a 2.5-kD polymer to pass,
      transport of a 5.0-kD molecule is greatly restricted. In addition, PEG chains
      gave greater reductions in pore conductance when covalently attached to the
      narrower regions of the lumen, permitting further definition of the interior of
      the pore. The procedures described here should be applicable to other pores and
      to related structures such as the vestibules of ion channels.

PMID- 11222630
TI  - Na(+) occupancy and Mg(2+) block of the n-methyl-d-aspartate receptor channel.
AB  - The effect of extracellular and intracellular Na(+) on the single-channel
      kinetics of Mg(2+) block was studied in recombinant NR1-NR2B NMDA receptor
      channels. Na(+) prevents Mg(2+) access to its blocking site by occupying two
      sites in the external portion of the permeation pathway. The occupancy of these
      sites by intracellular, but not extracellular, Na(+) is voltage-dependent. In the
      absence of competing ions, Mg(2+) binds rapidly (>10(8) M(-1)s(-1), with no
      membrane potential) to a site that is located 0.60 through the electric field
      from the extracellular surface. Occupancy of one of the external sites by Na(+)
      may be sufficient to prevent Mg(2+) dissociation from the channel back to the
      extracellular compartment. With no membrane potential; and in the absence of
      competing ions, the Mg(2+) dissociation rate constant is >10 times greater than
      the Mg(2+) permeation rate constant, and the Mg(2+) equilibrium dissociation
      constant is approximately 12 microM. Physiological concentrations of
      extracellular Na(+) reduce the Mg(2+) association rate constant approximately 40
      fold but, because of the "lock-in" effect, reduce the Mg(2+) equilibrium
      dissociation constant only approximately 18-fold.

PMID- 11222631
TI  - K(+) occupancy of the N-methyl-d-aspartate receptor channel probed by Mg(2+)
      block.
AB  - The single-channel kinetics of extracellular Mg(2+) block was used to probe K(+)
      binding sites in the permeation pathway of rat recombinant NR1/NR2B NMDA receptor
      channels. K(+) binds to three sites: two that are external and one that is
      internal to the site of Mg(2+) block. The internal site is approximately 0.84
      through the electric field from the extracellular surface. The equilibrium
      dissociation constant for this site for K(+) is 304 mM at 0 mV and with Mg(2+) in
      the pore. The occupancy of any one of the three sites by K(+) effectively
      prevents the association of extracellular Mg(2+). Occupancy of the internal site
      also prevents Mg(2+) permeation and increases (by approximately sevenfold) the
      rate constant for Mg(2+) dissociation back to the extracellular solution. Under
      physiological intracellular ionic conditions and at -60 mV, there is
      approximately 1,400-fold apparent decrease in the affinity of the channel for
      extracellular Mg(2+) and approximately 2-fold enhancement of the apparent voltage
      dependence of Mg(2+) block caused by the voltage dependence of K(+) occupancy of
      the external and internal sites.

PMID- 11222629
TI  - Oxidative regulation of large conductance calcium-activated potassium channels.
AB  - Reactive oxygen/nitrogen species are readily generated in vivo, playing roles in
      many physiological and pathological conditions, such as Alzheimer's disease and
      Parkinson's disease, by oxidatively modifying various proteins. Previous studies
      indicate that large conductance Ca(2+)-activated K(+) channels (BK(Ca) or Slo)
      are subject to redox regulation. However, conflicting results exist whether
      oxidation increases or decreases the channel activity. We used chloramine-T,
      which preferentially oxidizes methionine, to examine the functional consequences
      of methionine oxidation in the cloned human Slo (hSlo) channel expressed in
      mammalian cells. In the virtual absence of Ca(2+), the oxidant shifted the steady
      state macroscopic conductance to a more negative direction and slowed
      deactivation. The results obtained suggest that oxidation enhances specific
      voltage-dependent opening transitions and slows the rate-limiting closing
      transition. Enhancement of the hSlo activity was partially reversed by the enzyme
      peptide methionine sulfoxide reductase, suggesting that the upregulation is
      mediated by methionine oxidation. In contrast, hydrogen peroxide and cysteine
      specific reagents, DTNB, MTSEA, and PCMB, decreased the channel activity.
      Chloramine-T was much less effective when concurrently applied with the K(+)
      channel blocker TEA, which is consistent with the possibility that the target
      methionine lies within the channel pore. Regulation of the Slo channel by
      methionine oxidation may represent an important link between cellular electrical
      excitability and metabolism.

PMID- 11222632
TI  - synaptotagmin mutants reveal essential functions for the C2B domain in Ca2+
      triggered fusion and recycling of synaptic vesicles in vivo.
AB  - Synaptotagmin has been proposed to function as a Ca(2+) sensor that regulates
      synaptic vesicle exocytosis, whereas the soluble N-ethylmaleimide-sensitive
      factor attachment protein receptor (SNARE) complex is thought to form the core of
      a conserved membrane fusion machine. Little is known concerning the functional
      relationships between synaptotagmin and SNAREs. Here we report that synaptotagmin
      can facilitate SNARE complex formation in vitro and that synaptotagmin mutations
      disrupt SNARE complex formation in vivo. Synaptotagmin oligomers efficiently bind
      SNARE complexes, whereas Ca(2+) acting via synaptotagmin triggers cross-linking
      of SNARE complexes into dimers. Mutations in Drosophila that delete the C2B
      domain of synaptotagmin disrupt clathrin AP-2 binding and endocytosis. In
      contrast, a mutation that blocks Ca(2+)-triggered conformational changes in C2B
      and diminishes Ca(2+)-triggered synaptotagmin oligomerization results in a
      postdocking defect in neurotransmitter release and a decrease in SNARE assembly
      in vivo. These data suggest that Ca(2+)-driven oligomerization via the C2B domain
      of synaptotagmin may trigger synaptic vesicle fusion via the assembly and
      clustering of SNARE complexes.

PMID- 11222633
TI  - A ganglioside-specific sialyltransferase localizes to axons and non-Golgi
      structures in neurons.
AB  - To investigate the tissue distribution and subcellular localization of ST3GalV
      (CMP-NeuAc:lactosylceramide alpha2,3 sialyltransferase/GM3 synthase) in the adult
      mouse, we generated two antisera against mouse ST3GalV that were designated CS2
      (directed against amino acids K227-I272) and CS14 (directed against amino acids
      D308-H359). We previously reported that CS2 antiserum stains medial and trans
      Golgi cisternae in all cell types investigated. In neural tissue, however, CS14
      antiserum reveals a subpopulation of ST3GalV with a subcellular distribution
      complementary to CS2 antiserum. CS14 antiserum strongly stains axons in cortical,
      cerebellar, brainstem, and spinal cord tissue sections. The subcellular
      localization of neuronal ST3GalV is maintained in primary cultures of rat
      hippocampal neurons and in PC12 cells. In PC12 cells, ST3GalV localization
      evolves during NGF-induced differentiation such that a pool of enzyme leaves the
      Golgi for a distal compartment in conjunction with neurite outgrowth. In PC12
      cells transfected with an epitope-tagged form of ST3GalV, staining for the
      epitope tag coincides with expression of endogenous enzyme. The non-Golgi pool of
      ST3GalV does not colocalize with markers for the trans-Golgi network, endosome,
      or synaptic vesicles, nor is it detected on the cell surface. Distinct
      subpopulations of ST3GalV imply that ganglioside synthesis can occur outside of
      the Golgi or, alternatively, that a portion of the total ST3GalV pool subserves a
      nonenzymatic function. Significantly fewer transfected cells were found in PC12
      cultures treated with plasmid encoding ST3GalV than in cultures treated with
      control plasmid, indicating that the expression of ST3GalV in excess of
      endogenous levels results in either cell death or a decreased rate of cell
      division.

PMID- 11222634
TI  - Alpha-1-antichymotrypsin promotes beta-sheet amyloid plaque deposition in a
      transgenic mouse model of Alzheimer's disease.
AB  - Alpha(1)-antichymotrypsin (ACT), an acute-phase inflammatory protein, is an
      integral component of the amyloid deposits in Alzheimer's disease (AD) and has
      been shown to catalyze amyloid beta-peptide polymerization in vitro. We have
      investigated the impact of ACT on amyloid deposition in vivo by generating
      transgenic GFAP-ACT-expressing mice and crossing them with the PDGF-hAPP/V717F
      mice, which deposit amyloid in an age-dependent manner. The number of amyloid
      deposits measured by Congo Red birefringence was increased in the double
      ACT/amyloid precursor protein (APP) transgenic mice compared with transgenic mice
      that only expressed APP, particularly in the hippocampus where ACT expression was
      highest, and the increase was preceded by elevated total amyloid beta-peptide
      levels at an early age. Our data demonstrate that ACT promotes amyloid deposition
      and provide a specific mechanism by which inflammation and the subsequent
      upregulation of astrocytic ACT expression in AD brain contributes to AD
      pathogenesis.

PMID- 11222635
TI  - Molecular and physiological diversity of nicotinic acetylcholine receptors in the
      midbrain dopaminergic nuclei.
AB  - Nicotinic acetylcholine receptors (nAChRs) on dopaminergic (DA) and GABAergic
      (Gaba) projection neurons of the substantia nigra (SN) and ventral tegmental area
      (VTA) are characterized by single-cell RT-PCR and patch-clamp recordings in
      slices of rat and wild-type, beta2-/-, alpha4-/-, and alpha7-/- mice. The eight
      nAChR subunits expressed in these nuclei, alpha3-7 and beta2-4, contribute to
      four different types of nAChR-mediated currents. Most DA neurons in the SN and
      VTA express two nAChR subtypes. One is inhibited by dihydro-beta-erythroidine (2
      microm), alpha-conotoxin MII (10 nm), and methyllycaconitine (1 nm) but does not
      contain the alpha7 subunit; it possesses a putative alpha4alpha6alpha5(beta2)(2)
      composition. The other subtype is inhibited by dihydro-beta-erythroidine (2
      microm) and has a putative alpha4alpha5(beta2)(2) composition. Gaba neurons in
      the VTA exhibit a third subtype with a putative (alpha4)(2)(beta2)(3)
      composition, whereas Gaba neurons in the SN have either the putative
      (alpha4)(2)(beta2)(3) oligomer or the putative alpha4alpha6alpha5(beta2)(2)
      oligomer. The fourth subtype, a putative (alpha7)(5) homomer, is encountered in
      less than half of DA and Gaba neurons, in the SN as well as in the VTA. Neurons
      in the DA nuclei thus exhibit a diversity of nAChRs that might differentially
      modulate reinforcement and motor behavior.

PMID- 11222636
TI  - c-Src is required for glial cell line-derived neurotrophic factor (GDNF) family
      ligand-mediated neuronal survival via a phosphatidylinositol-3 kinase (PI-3K)
      dependent pathway.
AB  - The glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs),
      consisting of GDNF, neurturin, persephin, and artemin, signal via a
      multicomponent complex composed of Ret tyrosine kinase and the glycosyl
      phosphatidylinositol (GPI)-anchored coreceptors GFRalpha1-alpha4. In previous
      work we have demonstrated that the localization of Ret to membrane microdomains
      known as lipid rafts is essential for GDNF-induced downstream signaling,
      differentiation, and neuronal survival. Moreover, we have found that Ret
      interacts with members of the Src family kinases (SFK) only when it is localized
      to these microdomains. In the present work we show by pharmacological and genetic
      approaches that Src activity was necessary to elicit optimal GDNF-mediated
      signaling, neurite outgrowth, and survival. In particular, p60Src, but not the
      other ubiquitous SFKs, Fyn and Yes, was responsible for the observed effects.
      Moreover, Src appeared to promote neuronal survival via a phosphatidylinositol-3
      kinase (PI-3K)-dependent pathway because the PI-3K inhibitor LY294002 prevented
      GFL-mediated neuronal survival and prevented activated Src-mediated neuronal
      survival. In contrast, the inhibition of Src activity had no effects on NGF
      mediated survival, indicating that the requirement for Src was selective for GFL
      mediated neuronal survival. These data confirm the importance of protein-protein
      interactions between Ret and raft-associated proteins in the signaling pathways
      elicited by GDNF, and the data implicate Src as one of the major signaling
      molecules involved in GDNF-mediated bioactivity.

PMID- 11222637
TI  - Kv2 channels form delayed-rectifier potassium channels in situ.
AB  - A non inactivating potassium current known as the delayed rectifier plays a major
      role in membrane repolarization during an action potential. Whereas several
      candidate genes exist that code for potassium current, the identities of the
      molecular isotypes that are responsible in situ for membrane repolarization
      remain unidentified. We report that Kv2 channels play a major role in action
      potential repolarization. Kv2 channel elimination resulted in a reduction of the
      density of noninactivating potassium current and a prolonged impulse duration. In
      contrast, suppression of noninactivating current carried by Kv1 channels was much
      less effective in increasing action potential durations. Thus, whereas different
      potassium channels encode sustained potassium current, their contributions to
      action potential repolarization vary and require direct examination in situ. Our
      results indicate that Kv2 subunits function as classic delayed-rectifier channels
      in vertebrate neurons.

PMID- 11222638
TI  - Insulin-like growth factor-I overexpression attenuates cerebellar apoptosis by
      altering the expression of Bcl family proteins in a developmentally specific
      manner.
AB  - In studies of transgenic (Tg) mice that overexpress insulin-like growth factor-I
      (IGF-I) exclusively in the CNS, we demonstrated a dramatic increase in cerebellar
      granule cell number that appeared to be attributable predominantly to enhanced
      survival. IGF-I anti-apoptotic actions are well established in cultured neurons,
      but comparable studies in vivo are few. Using the same Tg mice, therefore, we set
      out to document IGF-I anti-apoptotic effects during cerebellar development and to
      probe IGF-I signaling mechanisms. Compared with cerebella (CBs) of non-Tg
      littermates, those of Tg mice had fewer apoptotic cells at postnatal day 7 (P7)
      and showed a similar tendency at P14 and P21. At each age studied, procaspase-3
      and caspase-3 were decreased in CBs of Tg mice. The caspase-3 decline was
      accompanied by decreases in the 85 kDa fragment of Poly(ADP-ribose) polymerase, a
      known product of caspase cleavage, suggesting decreased caspase activity. At P7
      decreased apoptosis in Tg mice was associated with increased expression of the
      anti-apoptotic Bcl genes, Bcl-x(L) and Bcl-2. The mRNA expression of the
      proapoptotic Bcl genes, Bax and Bad, also was increased, but no changes were
      observed in the abundance of their proteins. At P14 Bcl-xL and Bcl-2 expression
      were similar in normal and Tg mice; Bax mRNA was unchanged in Tg mice, but its
      protein abundance was decreased, and both Bad mRNA and protein abundance were
      decreased. At P21 Bcl-xL and Bcl-2 expression were unchanged, but Bax and Bad
      expression were decreased. Our data show that IGF-I exerts anti-apoptotic actions
      during cerebellar development, and thereby alters the magnitude of naturally
      occurring apoptosis. IGF-I appears to affect multiple steps in the apoptotic
      pathway in a developmentally specific manner. IGF-I decreases caspase-3
      availability and activity, increases the expression of anti-apoptotic Bcl-x(L)
      and Bcl-2 during early postnatal development, and decreases proapoptotic Bax and
      Bad expression at later developmental stages.

PMID- 11222639
TI  - Cytoplasmic domain mutations of the L1 cell adhesion molecule reduce L1-ankyrin
      interactions.
AB  - The neural adhesion molecule L1 mediates the axon outgrowth, adhesion, and
      fasciculation that are necessary for proper development of synaptic connections.
      L1 gene mutations are present in humans with the X-linked mental retardation
      syndrome CRASH (corpus callosum hypoplasia, retardation, aphasia, spastic
      paraplegia, hydrocephalus). Three missense mutations associated with CRASH
      syndrome reside in the cytoplasmic domain of L1, which contains a highly
      conserved binding region for the cytoskeletal protein ankyrin. In a cellular
      ankyrin recruitment assay that uses transfected human embryonic kidney (HEK) 293
      cells, two of the pathologic mutations located within the conserved SFIGQY
      sequence (S1224L and Y1229H) strikingly reduced the ability of L1 to recruit 270
      kDa ankyrinG protein that was tagged with green fluorescent protein (ankyrin-GFP)
      to the plasma membrane. In contrast, the L1 missense mutation S1194L and an L1
      isoform lacking the neuron-specific sequence RSLE in the cytoplasmic domain were
      as effective as RSLE-containing neuronal L1 in the recruitment of ankyrin-GFP.
      Ankyrin binding by L1 was independent of cell-cell interactions. Receptor
      mediated endocytosis of L1 regulates intracellular signal transduction, which is
      necessary for neurite outgrowth. In rat B35 neuroblastoma cell lines stably
      expressing L1 missense mutants, antibody-induced endocytosis was unaffected by
      S1224L or S1194L mutations but appeared to be enhanced by the Y1229H mutation.
      These results suggested a critical role for tyrosine residue 1229 in the
      regulation of L1 endocytosis. In conclusion, specific mutations within key
      residues of the cytoplasmic domain of L1 (Ser(1224), Tyr(1229)) destabilize
      normal L1-ankyrin interactions and may influence L1 endocytosis to contribute to
      the mechanism of neuronal dysfunction in human X-linked mental retardation.

PMID- 11222640
TI  - Hippocampal synaptic plasticity involves competition between Ca2+/calmodulin
      dependent protein kinase II and postsynaptic density 95 for binding to the NR2A
      subunit of the NMDA receptor.
AB  - NMDA receptor, Ca(2+)/calmodulin-dependent protein kinase II (alphaCaMKII), and
      postsynaptic density 95 (PSD-95) are three major components of the PSD fraction.
      Both alphaCaMKII and PSD-95 have been shown previously to bind NR2 subunits of
      the NMDA receptor complex. The nature and mechanisms of targeting to the NMDA
      receptor subunits are, however, not completely understood. Here we report that
      the C-terminal NR2A(S1389-V1464) sequence was sufficient to guarantee the
      association of both native and recombinant alphaCaMKII and PSD-95. PSD-95(54-256)
      was able to compete with the binding of both native and recombinant alphaCaMKII
      to the NR2A C-tail. Accordingly, alphaCaMKII(1-325) competes with both the native
      PSD-95 and the native kinase itself for the binding to NR2A. In addition,
      Ser/Ala1289 and Ser/Asp1289 point mutations on the unique CaMKII phosphosite of
      NR2A did not significantly influence the binding of native alphaCaMKII and PSD-95
      to the NR2A C-tail. Finally, the association-dissociation of alphaCaMKII and PSD
      95 to and from the NR2A C-tail was significantly modulated by activation of NMDA
      receptor achieved by either pharmacological tools or long-term potentiation
      induction, underlining the importance of dynamic and reciprocal interactions of
      NMDA receptor, alphaCaMKII, and PSD-95 in hippocampal synaptic plasticity.

PMID- 11222641
TI  - Differential expression of glutamate receptor subunits in the nervous system of
      Caenorhabditis elegans and their regulation by the homeodomain protein UNC-42.
AB  - In almost all nervous systems, rapid excitatory synaptic communication is
      mediated by a diversity of ionotropic glutamate receptors. In Caenorhabditis
      elegans, 10 putative ionotropic glutamate receptor subunits have been identified,
      a surprising number for an organism with only 302 neurons. Sequence analysis of
      the predicted proteins identified two NMDA and eight non-NMDA receptor subunits.
      Here we describe the complete distribution of these subunits in the nervous
      system of C. elegans. Receptor subunits were found almost exclusively in
      interneurons and motor neurons, but no expression was detected in muscle cells.
      Interestingly, some neurons expressed only a single subunit, suggesting that
      these may form functional homomeric channels. Conversely, interneurons of the
      locomotory control circuit (AVA, AVB, AVD, AVE, and PVC) coexpressed up to six
      subunits, suggesting that these subunits interact to generate a diversity of
      heteromeric glutamate receptor channels that regulate various aspects of worm
      movement. We also show that expression of these subunits in this circuit is
      differentially regulated by the homeodomain protein UNC-42 and that UNC-42 is
      also required for axonal pathfinding of neurons in the circuit. In wild-type
      worms, the axons of AVA, AVD, and AVE lie in the ventral cord, whereas in unc-42
      mutants, the axons are anteriorly, laterally, or dorsally displaced, and the
      mutant worms have sensory and locomotory defects.

PMID- 11222642
TI  - Altered electrical properties in Drosophila neurons developing without synaptic
      transmission.
AB  - We examine the role of synaptic activity in the development of identified
      Drosophila embryonic motorneurons. Synaptic activity was blocked by both pan
      neuronal expression of tetanus toxin light chain (TeTxLC) and by reduction of
      acetylcholine (ACh) using a temperature-sensitive allele of choline
      acetyltransferase (Cha(ts2)). In the absence of synaptic activity, aCC and RP2
      motorneurons develop with an apparently normal morphology and retain their
      capacity to form synapses. However, blockade of synaptic transmission results in
      significant changes in the electrical phenotype of these neurons. Specifically,
      increases are seen in both voltage-gated inward Na(+) and voltage-gated outward
      K(+) currents. Voltage-gated Ca(2+) currents do not change. The changes in
      conductances appear to promote neuron excitability. In the absence of synaptic
      activity, the number of action potentials fired by a depolarizing ramp (-60 to
      +60 mV) is increased and, in addition, the amplitude of the initial action
      potential fired is also significantly larger. Silencing synaptic input to just
      aCC, without affecting inputs to other neurons, demonstrates that the capability
      to respond to changing levels of synaptic excitation is intrinsic to these
      neurons. The alteration to electrical properties are not permanent, being
      reversed by restoration of normal synaptic function. Whereas our data suggest
      that synaptic activity makes little or no contribution to the initial formation
      of embryonic neural circuits, the electrical development of neurons that
      constitute these circuits seems to depend on a process that requires synaptic
      activity.

PMID- 11222643
TI  - Endogenous serotonin contributes to a developmental decrease in long-term
      potentiation in the rat visual cortex.
AB  - The primary visual cortex shows synaptic plasticity during a postnatal "critical
      period," and its plasticity declines with development. Indeed, we found a
      developmental decrease in the induction of long-term potentiation (LTP) in the
      rat visual cortex. In visual cortex slices obtained from 2- to 3-week-old rats,
      tetanic stimulation (100 Hz for 1 sec, twice at an interval of 30 sec) of the
      white matter reproducibly induced LTP of field potentials in layer II/III.
      However, in slices from 5-week-old rats, the same tetanic stimulation failed to
      induce LTP. We hypothesized that endogenous serotonin (5-HT) is responsible for
      the developmental decrease in visual cortex LTP, because the induction of visual
      cortex LTP was suppressed by the addition of exogenous 5-HT (10 microm) and
      because the amount of 5-HT in the visual cortex increased during development. To
      test this hypothesis, we investigated the effect of methysergide, a 5-HT receptor
      antagonist, on the induction of visual cortex LTP. When visual cortex slices from
      5-week-old rats were perfused with 50 microm methysergide, tetanic stimulation of
      the white matter induced robust LTP in layer II/III. Furthermore, serotonergic
      neurons were lesioned by intracerebroventricular injection of 5,7
      dihydroxytryptamine (5,7-DHT). LTP was induced in visual cortex slices from 5,7
      DHT-treated, 5-week-old rats. These results suggest that the induction of visual
      cortex LTP in 5-week-old rats is suppressed by endogenous 5-HT. 5-HT may be a
      factor that determines a critical period for synaptic plasticity in the rat
      visual cortex.

PMID- 11222644
TI  - Induction of astrocyte differentiation by endothelial cells.
AB  - Here we have investigated the mechanisms that control astrocyte differentiation
      within the developing rat optic nerve. Astrocytes are normally generated by
      astrocyte precursor cells within the embryonic optic nerve. We show that there is
      a close temporal and spatial correlation between endothelial and astrocyte
      differentiation. We tested the potential role of endothelial cells in inducing
      astrocyte differentiation by developing an immunopanning method to highly purify
      endothelial cells from developing optic nerves. We show that the purified
      endothelial cells, but not other embryonic optic nerve cell types, strongly
      induce the differentiation of purified astrocyte precursor cells into astrocytes
      in vitro. Leukemia inhibitory factor (LIF) and LIF receptors have been implicated
      previously in astrocyte differentiation in vivo. We show that purified
      endothelial cells express LIF mRNA and that their ability to induce astrocyte
      differentiation is prevented by a neutralizing anti-LIF, but not anti-ciliary
      neurotrophic factor, antiserum. These findings demonstrate a role for endothelial
      cells in inducing astrocyte differentiation. The induction of astrocyte
      differentiation by endothelial cells makes sense phylogenetically, anatomically,
      and functionally, because astrocytes evolved concurrently with brain vasculature
      and ensheathe capillaries throughout the brain. The ability to purify and culture
      astrocytes and endothelial cells should provide an excellent model system for
      future studies of blood-brain barrier development.

PMID- 11222645
TI  - The N-terminal leucine-rich regions in Slit are sufficient to repel olfactory
      bulb axons and subventricular zone neurons.
AB  - The Slit proteins are a new family of secreted guidance cues involved in axon
      guidance and neuronal migration. Each mammalian Slit protein contains >1400 amino
      acid residues, with four leucine-rich regions (LRRs), nine epidermal growth
      factor repeats, a laminin G domain, and a C-terminal cysteine-rich domain. A
      receptor for Slit is the transmembrane protein Roundabout (Robo), whose
      extracellular part contains five Ig domains and three fibronectin type III
      repeats. We report here that the LRRs in Slit are sufficient for binding to the
      Ig domains of Robo. Mutant forms of Slit containing only the LRRs function as
      chemorepellents for axons projecting from the olfactory bulb both in vitro and in
      the telencephalon. The LRRs can repel neurons migrating from the anterior
      subventricular zone (SVZa) to the olfactory bulb in brain slices isolated from
      neonatal rodents. However, the LRRs do not show repulsive effects on the SVZa
      neurons migrating in collagen gels. Our results indicate that the same LRRs are
      sufficient for guiding both axon projection and neuronal migration and suggest
      that the other regions in the Slit proteins may be involved in regulating the
      diffusion and distribution of the Slit proteins. The fact that the same domains
      are involved in guiding axon projection and neuronal migration further
      strengthens the idea of a conserved guidance mechanism for these important
      processes.

PMID- 11222646
TI  - Chronic NMDA receptor blockade from birth increases the sprouting capacity of
      ipsilateral retinocollicular axons without disrupting their early segregation.
AB  - We have investigated the role of the NMDA glutamate receptor (NMDAR) in the
      genesis and regulation of structural plasticity during synaptogenesis in the
      visual layers of the rat superior colliculus (sSC). In this neuropil, three
      projections compete for synaptic space during development. By fluorescently
      labeling the projections of both eyes and imaging them with confocal microscopy,
      we can quantify the sprouting of the ipsilateral retinal projection that follows
      removal of a portion of the contralateral retinal and/or corticocollicular
      projection. Using these techniques we have studied the effects of NMDAR blockade
      under different levels of competition. NMDARs were chronically blocked from birth
      [postnatal day 0 (P0)] by suspending the competitive antagonist 2-amino-5
      phosphonopentanoic acid in the slow release plastic Elvax, a slab of which was
      implanted over the sSC. Such treatment alone does not impair the normal
      segregation of the retinal projections. However, if sprouting of the ipsilateral
      projection is initiated with a small contralateral retinal lesion at P6, this
      sprouting can be further increased by blocking NMDARs from birth. Sprouting of
      the ipsilateral retinal projection is also induced by retinal lesions made at
      P10/P11, but NMDAR blockade does not augment the sprouting induced by this later
      lesion. However, when combined with simultaneous ablation of the ipsilateral
      visual cortex, P10/P11 lesions show increased sprouting after NMDAR blockade.
      These data indicate that P0 NMDAR blockade does not eliminate synaptic
      competition in the sSC. Instead, early elimination of NMDAR function appears to
      facilitate sprouting that is gated in a stepwise manner by the other visual
      afferents.

PMID- 11222647
TI  - Activation of phosphatidylinositol-3 kinase (PI-3K) and extracellular regulated
      kinases (Erk1/2) is involved in muscarinic receptor-mediated DNA synthesis in
      neural progenitor cells.
AB  - Muscarinic acetylcholine receptor (mAChR), a member of the G-protein-coupled
      receptors (GPCRs) gene superfamily, has been shown to mediate the effects of
      acetylcholine on differentiation and proliferation in the CNS. However, the
      mechanism or mechanisms whereby mAChRs regulate cell proliferation remain poorly
      understood. Here we show that in vitro bFGF-expanded neural progenitor cells
      dissociated from rat cortical neuroepithelium express muscarinic acetylcholine
      receptor subtype mRNAs. We demonstrate that stimulation of these mAChRs with
      carbachol, a muscarinic agonist, activated extracellular-regulated kinases
      (Erk1/2) and phosphatidylinositol-3 kinase (PI-3K). This, in turn, stimulated DNA
      synthesis in neural progenitor cells. MEK inhibitor PD98059 and PI-3K inhibitors
      wortmannin and LY294002 inhibited a carbachol-induced increase in DNA synthesis.
      These findings indicate that the activation of both PI-3 kinase and MEK signaling
      pathways via muscarinic receptors is involved in stimulating DNA synthesis in the
      neural progenitor cells during early neurogenesis.

PMID- 11222648
TI  - Detailed field pattern is intrinsic to the embryonic mouse hippocampus early in
      neurogenesis.
AB  - There is accumulating evidence that the mammalian cerebral cortex is regionally
      specified early in neurogenesis. However, the degree and scale of the regional
      pattern that is intrinsic to different parts of the cortical primordium remains
      unclear. Here, we show that detailed patterning-the accurate positioning of
      several areas or fields-is intrinsic to the part of the primordium that generates
      the hippocampus. A caudomedial portion of the cortical primordium, the site from
      which the hippocampus arises, was isolated from potential extrinsic patterning
      cues by maintaining it in explant culture. Explants were prepared at embryonic
      day (E) 12.5, which is early in hippocampal neurogenesis in the mouse and 3 d
      before individual fields are seen by differential gene expression. Allowed to
      develop for 3 d in vitro, E12.5 explants upregulate field-specific patterns of
      gene expression with striking temporal and spatial accuracy. Possible sources of
      patterning signals intrinsic to the explants were evaluated by removing the
      cortical hem or presumptive extrahippocampal cortex from the explants. To expose
      cells to different local positional cues, explant fragments were grafted into
      ectopic positions in a larger explant. None of these manipulations altered the
      development of patterned, field-specific gene expression. Finally, explants
      harvested at E10.5 also upregulate field-specific gene expression, although less
      robustly. Some hippocampal patterning information is therefore intrinsic to the
      caudomedial cortical primordium at the time that the first hippocampal neurons
      are born at E10.5. By E12.5, hippocampal field patterning appears to be well
      established and resistant to the manipulation of several potential intrinsic
      cues.

PMID- 11222650
TI  - Hemispheric lateralization in the cortical motor preparation for human
      vocalization.
AB  - To investigate the cortical information processing during the preparation of
      vocalization, we performed transcranial magnetic stimulation (TMS) over the
      cortex while the subjects prepared to produce voice in response to a visual cue.
      The control reaction time (RT) of vocalization without TMS was 250-350 msec. TMS
      prolonged RT when it was delivered up to 150-200 msec before the expected onset
      of voice (EOV). The largest delay of RT was induced bilaterally over points 6 cm
      to the left and right of the vertex (the left and right motor areas), resulting
      in 10-20% prolongation of RT. During the early phase of prevocalization period
      (50-100 msec before EOV), the delay induced over the left motor area was slightly
      larger than that induced over the right motor area, whereas, during the late
      phase (0-50 msec before EOV), it was significantly larger over the right motor
      area. Bilateral and simultaneous TMS of the left and right motor areas induced
      delays not significantly different from that induced by unilateral TMS during the
      early phase, but induced a large delay well in excess of the latter during the
      late phase. Thus, during the cortical preparation for human vocalization,
      alternation of hemispheric lateralization takes place between the bilateral motor
      cortices near the facial motor representations, with mild left hemispheric
      predominance at the early phase switching over to robust right hemispheric
      predominance during the late phase. Our results also suggested involvement of the
      motor representation of respiratory muscles and also of supplementary motor
      cortex.

PMID- 11222649
TI  - Regulation of mouse kappa opioid receptor gene expression by retinoids.
AB  - The effect of retinoids on the expression of kappa opioid receptor (KOR) gene was
      examined in normal and transgenic animals. KOR-lacZ transgene expression was
      specifically elevated in KOR-positive areas of the developing CNS by depleting
      vitamin A from animal diets. The endogenous KOR mRNA species, including all three
      isoforms, were also upregulated by depleting vitamin A in developing animals.
      Change in the expression of isoforms a and b is similar in prenatal stages but
      differs during postnatal development. Interestingly, upregulation of isoform c is
      most significant postnatally. The regulation of KOR gene by vitamin A was
      substantiated in a mouse embryonal carcinoma P19 culture system in which retinoic
      acid (RA), the most potent ingredient of vitamin A, was able to suppress the
      expression of all the three KOR isoforms and KOR protein. The RA-mediated
      suppression was blocked by an RA receptor antagonist and a histone deacetylase
      (HDAC) inhibitor. By using a reporter transfection assay in P19 cells, the
      potential genetic element responsible for RA-mediated suppression of KOR gene
      expression was located to intron 1 of the mouse KOR gene, which could also be
      blocked by HDAC inhibitor. Furthermore, suppression of KOR gene expression by RA
      in P19 cells appeared to be an indirect event and required protein synthesis. A
      role of RA in KOR gene regulation during developmental stages was discussed.

PMID- 11222651
TI  - Neural network partitioning by NO and cGMP.
AB  - The stomatogastric ganglion (STG) of the crab Cancer productus contains
      approximately 30 neurons arrayed into two different networks (gastric mill and
      pyloric), each of which produces a distinct motor pattern in vitro. Here we show
      that the functional division of the STG into these two networks requires intact
      NO-cGMP signaling. Multiple nitric oxide synthase (NOS)-like proteins are
      expressed in the stomatogastric nervous system, and NO appears to be released as
      an orthograde transmitter from descending inputs to the STG. The receptor of NO,
      a soluble guanylate cyclase (sGC), is expressed in a subset of neurons in both
      motor networks. When NO diffusion or sGC activation are blocked within the
      ganglion, the two networks combine into a single conjoint circuit. The gastric
      mill motor rhythm breaks down, and several gastric neurons pattern switch and
      begin firing in pyloric time. The functional reorganization of the STG is both
      rapid and reversible, and the gastric mill motor rhythm is restored when the
      ganglion is returned to normal saline. Finally, pharmacological manipulations of
      the NO-cGMP pathway are ineffective when descending modulatory inputs to the STG
      are blocked. This suggests that the NO-cGMP pathway may interact with other
      biochemical cascades to partition rhythmic motor output from the ganglion.

PMID- 11222652
TI  - Spontaneous hemorrhagic stroke in a mouse model of cerebral amyloid angiopathy.
AB  - A high risk factor for spontaneous and often fatal lobar hemorrhage is cerebral
      amyloid angiopathy (CAA). We now report that CAA in an amyloid precursor protein
      transgenic mouse model (APP23 mice) leads to a loss of vascular smooth muscle
      cells, aneurysmal vasodilatation, and in rare cases, vessel obliteration and
      severe vasculitis. This weakening of the vessel wall is followed by rupture and
      bleedings that range from multiple, recurrent microhemorrhages to large
      hematomas. Our results demonstrate that, in APP transgenic mice, the
      extracellular deposition of neuron-derived beta-amyloid in the vessel wall is the
      cause of vessel wall disruption, which eventually leads to parenchymal
      hemorrhage. This first mouse model of CAA-associated hemorrhagic stroke will now
      allow development of diagnostic and therapeutic strategies.

PMID- 11222653
TI  - Circulating insulin-like growth factor I mediates exercise-induced increases in
      the number of new neurons in the adult hippocampus.
AB  - Although the physiological significance of continued formation of new neurons in
      the adult mammalian brain is still uncertain, therapeutic strategies aimed to
      potentiate this process show great promise. Several external factors, including
      physical exercise, increase the number of new neurons in the adult hippocampus,
      but underlying mechanisms are not yet known. We recently found that exercise
      stimulates uptake of the neurotrophic factor insulin-like growth factor I (IGF-I)
      from the bloodstream into specific brain areas, including the hippocampus. In
      addition, IGF-I participates in the effects of exercise on hippocampal c-fos
      expression and mimics several other effects of exercise on brain function.
      Because subcutaneous administration of IGF-I to sedentary adult rats markedly
      increases the number of new neurons in the hippocampus, we hypothesized that
      exercise-induced brain uptake of blood-borne IGF-I could mediate the stimulatory
      effects of exercise on the adult hippocampus. Thus, we blocked the entrance of
      circulating IGF-I into the brain by subcutaneous infusion of a blocking IGF-I
      antiserum to rats undergoing exercise training. The resulting inhibition of brain
      uptake of IGF-I was paralleled by complete inhibition of exercise-induced
      increases in the number of new neurons in the hippocampus. Exercising rats
      receiving an infusion of nonblocking serum showed normal increases in the number
      of new hippocampal neurons after exercise. Thus, increased uptake of blood-borne
      IGF-I is necessary for the stimulatory effects of exercise on the number of new
      granule cells in the adult hippocampus. Taken together with previous results, we
      conclude that circulating IGF-I is an important determinant of exercise-induced
      changes in the adult brain.

PMID- 11222654
TI  - Accumulation of hippocampal place fields at the goal location in an annular
      watermaze task.
AB  - To explore the plastic representation of information in spatially selective
      hippocampal pyramidal neurons, we made multiple single-unit recordings in rats
      trained to find a hidden platform at a constant location in a hippocampal
      dependent annular watermaze task. Hippocampal pyramidal cells exhibited place
      related firing in the watermaze. Place fields tended to accumulate near the
      platform, even in probe trials without immediate escape. The percentage of cells
      with peak activity around the hidden platform was more than twice the percentage
      firing in equally large areas elsewhere in the arena. The effect was independent
      of the actual position of the platform in the room frame. It was dissociable from
      ongoing motor behavior and was not related to linear or angular speed, swim
      direction, or variation in hippocampal theta activity. There was no accumulation
      of firing in any particular region in rats that were trained with a variable
      platform location. These training-dependent effects suggest that regions of
      particular behavioral significance may be over-represented in the hippocampal
      spatial map, even when these regions are completely unmarked.

PMID- 11222655
TI  - Local specification of relative strengths of synapses between different abdominal
      stretch-receptor axons and their common target neurons.
AB  - Stretch-receptor (SR) axons form a parallel array of 20 excitatory synapses with
      target neurons in the crayfish CNS. In each postsynaptic neuron, EPSPs from
      different SR axons differ significantly in size. These amplitudes are correlated
      with the segment in which each axon originates and form a segmental gradient of
      synaptic excitation in individual postsynaptic neurons. These differences might
      arise postsynaptically because of differential postsynaptic attenuation or
      presynaptically because of local regulation of the strength of each synapse. To
      examine these possibilities, we stimulated each SR axon separately and studied
      integration of its EPSPs in an identified neuron, Flexor Inhibitor 6 (FI6).
      Transmission from SR axons to FI6 was chemical and direct: EPSPs were accompanied
      by an increased postsynaptic conductance, were affected by extracellular Ca(2+),
      and showed frequency-dependent depression. EPSPs from different SR axons summed
      linearly. The rise times of EPSPs from different SR axons were not significantly
      different. We also filled individual SR axons and FI6 neurons and mapped and
      counted their points of contact. Each SR axon contacted each FI6 bilaterally, and
      contacts of SR axons from different segments were intermingled on FI6. SR axons
      that made the strongest synapses made more points-of-contact with FI6. These
      results imply that differences in strength do not arise because of differential
      postsynaptic attenuation of EPSPs, but rather because certain SR axons
      predictably make more points of contact with FI6 than do others. Thus, this
      gradient in excitation requires that each synapse be regulated by an exchange
      between the SR axon and its target neuron.

PMID- 11222656
TI  - Fos expression in orexin neurons varies with behavioral state.
AB  - The neuropeptide orexin (also known as hypocretin) is hypothesized to play a
      critical role in the regulation of sleep-wake behavior. Lack of orexin produces
      narcolepsy, which is characterized by poor maintenance of wakefulness and
      intrusions of rapid eye movement (REM) sleep or REM sleep-like phenomena into
      wakefulness. Orexin neurons heavily innervate many aminergic nuclei that promote
      wakefulness and inhibit REM sleep. We hypothesized that orexin neurons should be
      relatively active during wakefulness and inactive during sleep. To determine the
      pattern of activity of orexin neurons, we recorded sleep-wake behavior, body
      temperature, and locomotor activity under various conditions and used double
      label immunohistochemistry to measure the expression of Fos in orexin neurons of
      the perifornical region. In rats maintained on a 12 hr light/dark cycle, more
      orexin neurons had Fos immunoreactive nuclei during the night period; in animals
      housed in constant darkness, this activation still occurred during the subjective
      night. Sleep deprivation or treatment with methamphetamine also increased Fos
      expression in orexin neurons. In each of these experiments, Fos expression in
      orexin neurons correlated positively with the amount of wakefulness and
      correlated negatively with the amounts of non-REM and REM sleep during the
      preceding 2 hr. In combination with previous work, these results suggest that
      activation of orexin neurons may contribute to the promotion or maintenance of
      wakefulness. Conversely, relative inactivity of orexin neurons may allow the
      expression of sleep.

PMID- 11222657
TI  - Organization of olivocerebellar activity in the absence of excitatory
      glutamatergic input.
AB  - The olivocerebellar system has been proposed to function as a timing device for
      motor coordination in which inferior olivary neurons act as coupled oscillators
      that spontaneously generate rhythmic and synchronous activity. However, the
      inferior olive receives excitatory afferents, which can also drive the activity
      of these neurons. The extent to which the olivocerebellar system can
      intrinsically generate synchronous activity and olivary neurons act as neuronal
      oscillators has not been determined. To investigate this issue, multiple
      electrode recordings of complex spike (CS) activity were obtained from 236 crus
      2a Purkinje cells in anesthetized rats. Intraolivary injections of the glutamate
      antagonists 6-cyano-7-nitroquinoxaline-2,3-dione or 1,2,3,4-tetrahydro-6-nitro
      2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium were made, and the resulting
      changes in CS activity were determined. Loss of evoked CS responses to motor
      cortex stimulation or perioral tactile stimulation was used to measure the
      efficacy of the block. Block of glutamatergic input decreased the average CS
      firing rate by approximately 50% but did not abolish spontaneous CS activity. The
      remaining CS activity was significantly more rhythmic than that in control. The
      patterns of synchrony were similar to those found in control conditions (i.e.,
      synchronous CSs primarily occurred among Purkinje cells located within the same
      approximately 250-microm-wide rostrocaudally oriented cortical strip); however,
      this normal banding pattern was enhanced. These changes in CS activity were not
      observed with vehicle injections. The results suggest that excitatory afferent
      activity disrupts olivary oscillations and support the hypotheses that olivary
      neurons are capable of acting as neuronal oscillators and that synchronous CS
      activity results from electrotonic coupling of olivary neurons.

PMID- 11222658
TI  - Correlated firing in macaque visual area MT: time scales and relationship to
      behavior.
AB  - We studied the simultaneous activity of pairs of neurons recorded with a single
      electrode in visual cortical area MT while monkeys performed a direction
      discrimination task. Previously, we reported the strength of interneuronal
      correlation of spike count on the time scale of the behavioral epoch (2 sec) and
      noted its potential impact on signal pooling (Zohary et al., 1994). We have now
      examined correlation at longer and shorter time scales and found that pair-wise
      cross-correlation was predominantly short term (10-100 msec). Narrow, central
      peaks in the spike train cross-correlograms were largely responsible for
      correlated spike counts on the time scale of the behavioral epoch. Longer-term
      (many seconds to minutes) changes in the responsiveness of single neurons were
      observed in auto-correlations; however, these slow changes in time were on
      average uncorrelated between neurons. Knowledge of the limited time scale of
      correlation allowed the derivation of a more efficient metric for spike count
      correlation based on spike timing information, and it also revealed a potential
      relative advantage of larger neuronal pools for shorter integration times.
      Finally, correlation did not depend on the presence of the visual stimulus or the
      behavioral choice of the animal. It varied little with stimulus condition but was
      stronger between neurons with similar direction tuning curves. Taken together,
      our results strengthen the view that common input, common stimulus selectivity,
      and common noise are tightly linked in functioning cortical circuits.

PMID- 11222659
TI  - Contextual modulation in primary visual cortex of macaques.
AB  - Recent studies have suggested that V1 neurons extract figures from their
      backgrounds, in that they respond better to interior features of figures than to
      equivalent features of background stimuli. This is reportedly true even when the
      figure boundaries are distant from the borders of the classical receptive field
      (RF). To test the role of V1 neurons in figure-ground segregation, we recorded
      their responses to texture figures on texture backgrounds, centered on the RF.
      The texture elements of the figures remained identical across trials, and figure
      boundaries were defined by orientation differences between the elements in the
      background texture relative to elements in the figure. For nearly all neurons
      (98/102), responses to a large texture figure did not differ from the responses
      to a uniform-texture background. Although many neurons gave enhanced responses to
      texture boundaries, this occurred only when the boundaries were within or close
      to the RF borders. Similar effects were found in V2. For neurons in V1, the
      limited spatial extent of the contextual modulation was not increased either at
      low stimulus contrast or when the animal was rewarded for detecting an
      orientation-defined figure. Thus, V1 neurons appear to signal texture boundaries
      rather than figures per se. Unexpectedly, many V1 neurons gave significant long
      latency responses to texture stimuli located entirely outside the classical RF,
      up to 5 degrees from the RF border in some cases. However, these responses did
      not depend on the stimulus forming a figure that contained the RF. Although V1
      neurons are influenced by stimuli outside the classical RF, they do not appear to
      segregate figures from ground.

PMID- 11222660
TI  - Specific roles of NMDA and AMPA receptors in direction-selective and spatial
      phase-selective responses in visual cortex.
AB  - Cells in the superficial layers of primary visual cortex (area 17) are
      distinguished by feedforward input from thalamic-recipient layers and by massive
      recurrent excitatory connections between neighboring cells. The connections use
      glutamate as transmitter, and the postsynaptic cells contain both NMDA and AMPA
      receptors. The possible role of these receptor types in generating emergent
      responses of neurons in the superficial cortical layers is unknown. Here, we show
      that NMDA and AMPA receptors are both involved in the generation of direction
      selective responses in layer 2/3 cells of area 17 in cats. NMDA receptors
      contribute prominently to responses in the preferred direction, and their
      contribution to responses in the nonpreferred direction is reduced significantly
      by GABAergic inhibition. AMPA receptors decrease spatial phase-selective simple
      cell responses and generate phase-invariant complex cell responses.

PMID- 11222661
TI  - Hippocampal inactivation disrupts contextual retrieval of fear memory after
      extinction.
AB  - Recent studies implicate the hippocampus in contextual memory retrieval. The
      present experiments explore this possibility by examining the impact of
      reversible inactivation of the dorsal hippocampus (DH) on the context-specific
      expression of extinction. In experiment 1, rats were conditioned to fear a tone
      conditional stimulus (CS) and subsequently extinguished either in the same
      context as conditioning or in a novel context. A third group of rats underwent
      fear conditioning but did not receive extinction. After extinction, conditional
      fear to the tone CS was assessed in the conditioning context by measuring
      freezing. Rats extinguished in the conditioning context exhibited low levels of
      freezing, whereas those extinguished in a different context and those that
      received no extinction showed high levels of freezing. This indicates that the
      expression of extinction is context-specific. In experiment 2, the context
      specific expression of extinction was disrupted by infusion of muscimol, a
      GABA(A) receptor agonist, into the DH. Rats that received muscimol infusions into
      the DH showed little freezing to the tone CS, regardless of whether the CS had
      been extinguished in the testing context or another context. In experiment 3,
      intrahippocampal muscimol infusions did not disrupt the expression of conditional
      freezing to the tone CS in rats that did not receive extinction. Thus, muscimol
      infusion into the DH produced a selective impairment in the context-specific
      expression of extinction. These results extend findings from other behavioral
      paradigms and provide additional support for a role for the hippocampus in
      contextual memory retrieval.

PMID- 11222662
TI  - Differential expression of synaptic and nonsynaptic mechanisms underlying
      stimulus-induced gamma oscillations in vitro.
AB  - Gamma frequency oscillations occur in hippocampus in vitro after brief tetani
      delivered to afferent pathways. Previous reports have characterized these
      oscillations as either (1) trains of GABA(A) inhibitory synaptic events mediated
      by depolarization of both pyramidal cells and interneurons at least in part
      mediated by metabotropic glutamate and acetylcholine receptors, or (2) field
      potential oscillations occurring in the near absence of an inhibitory synaptic
      oscillation when cells are driven by depolarizing GABA responses and local
      synchrony is produced by field effects. The aim of this study was to investigate
      factors involved in the differential expression of these synaptically and
      nonsynaptically gated oscillations. Field effects were undetectable in control
      recordings but manifested when slices were perfused with hypo-osmotic solutions
      or a reduced level of normal perfusate. These manipulations also reduced the
      amplitude of the train of inhibitory synaptic events associated with an
      oscillation and enhanced the depolarizing GABA component underlying the post
      tetanic depolarization. The resulting field oscillation was still dependent, at
      least in part, on inhibitory synaptic transmission, but spatiotemporal aspects of
      the oscillation were severely disrupted. These changes were also accompanied by
      an increase in estimated [K(+)](o) compared with control. We suggest that
      nonsynaptic oscillations occur under conditions also associated with epileptiform
      activity and constitute a phenomenon that is distinct from synaptically gated
      oscillations. The latter remain a viable model for in vivo oscillations of
      cognitive relevance.

PMID- 11222663
TI  - Contribution of postsynaptic Ca2+ to the induction of post-tetanic potentiation
      in the neural circuit for siphon withdrawal in Aplysia.
AB  - Recent studies in Aplysia have revealed a novel postsynaptic Ca(2+) component to
      posttetanic potentiation (PTP) at the siphon sensory to motor neuron (SN-MN)
      synapse. Here we asked whether the postsynaptic Ca(2+) component of PTP was a
      special feature of the SN-MN synapse, and if so, whether it reflected a unique
      property of the SN or the MN. We examined whether postsynaptic injection of BAPTA
      reduced PTP at SN synapses onto different postsynaptic targets by comparing PTP
      at SN-MN and SN-interneuron (L29) synapses. We also examined PTP at L29-MN
      synapses. Postsynaptic BAPTA reduced PTP only at the SN-MN synapse; it did not
      affect PTP at either the SN-L29 or the L29-MN synapse, indicating that the SN and
      the MN do not require postsynaptic Ca(2+) for PTP with all other synaptic
      partners. The postsynaptic Ca(2+) component of PTP is present at other Aplysia SN
      MN synapses; tail SN-MN synapses also showed reduced PTP when the MN was injected
      with BAPTA. Surprisingly, in both tail and siphon SN-MN synapses, there was an
      inverse relationship between the initial size of the EPSP and the postsynaptic
      component to PTP; only the initially weak SN-MN synapses showed a BAPTA-sensitive
      component. Homosynaptic depression of initially strong SN-MN synapses into the
      size range of initially weak synapses did not confer postsynaptic Ca(2+)
      sensitivity to PTP. Finally, the postsynaptic Ca(2+) component of PTP could be
      induced in the presence of APV, indicating that it is not mediated by NMDA
      receptors. These results suggest a dual model for PTP at the SN-MN synapse, in
      which a postsynaptic Ca(2+) contribution summates with the conventional
      presynaptic mechanisms to yield an enhanced form of PTP.

PMID- 11222664
TI  - Direct activation of rat spinal dorsal horn neurons by prostaglandin E2.
AB  - Whole-cell patch-clamp and intracellular recording techniques have been used to
      study the action of prostaglandin E2 (PGE2) on neurons in adult rat transverse
      spinal cord slices. Bath-applied PGE2 (1-20 microm) induced an inward current or
      membrane depolarization in the majority of deep dorsal horn neurons (laminas III
      VI; 83 of 139 cells), but only in a minority of lamina II neurons (6 of 53
      cells). PGE2 alone never elicited spontaneous action potentials; however, it did
      convert subthreshold EPSPs to suprathreshold, leading to action potential
      generation. PGE2-induced inward currents were unaffected by perfusion with either
      a Ca(2+)-free/high Mg(2+) (5 mm) solution or tetrodotoxin (1 microm), indicating
      a direct postsynaptic action. Both 17-phenyl trinor prostaglandin E2 (an EP1
      agonist) and sulprostone (an EP3 agonist) had little effect on membrane current,
      whereas butaprost methyl ester (an EP2 agonist) mimicked the effect of PGE2.
      Depolarizing responses to PGE2 were associated with a decrease in input
      resistance, and the amplitude of inward current was decreased as the holding
      potential was depolarized. PGE2-induced inward currents were reduced by
      substitution of extracellular Na(+) with N-methyl-d-glucamine and inhibited by
      flufenamic acid (50-200 microm), which is compatible with activation of a
      nonselective cation channel. These results suggest that PGE2, acting via an EP2
      like receptor, directly depolarizes spinal neurons. Moreover, these findings
      imply an involvement of spinal cord-generated prostanoids in modulating sensory
      processing through an alteration in dorsal horn neuronal excitability.

PMID- 11222665
TI  - Discharge profiles of ventral tegmental area GABA neurons during movement,
      anesthesia, and the sleep-wake cycle.
AB  - Although mesolimbic dopamine (DA) transmission has been implicated in behavioral
      and cortical arousal, DA neurons in the ventral tegmental area (VTA) and
      substantia nigra pars compacta (SNc) are not significantly modulated by
      anesthetics or the sleep-wake cycle. However, VTA and SN non-DA neurons evince
      increased firing rates during active wakefulness (AW) and rapid eye movement
      (REM) sleep, relative to quiet wakefulness. Here we describe the effects of
      movement, select anesthetics, and the sleep-wake cycle on the activity of a
      homogeneous population of VTA GABA-containing neurons during normal sleep and
      after 24 hr sleep deprivation. In freely behaving rats, VTA GABA neurons were
      relatively fast firing (29 +/- 6 Hz during AW), nonbursting neurons that
      exhibited markedly increased activity during the onset of discrete movements.
      Adequate anesthesia produced by administration of chloral hydrate, ketamine, or
      halothane significantly reduced VTA GABA neuron firing rate and converted their
      activity into phasic 0.5-2.0 sec ON/OFF periods. VTA GABA neuron firing rate
      decreased 53% during slow-wave sleep (SWS) and increased 79% during REM, relative
      to AW; however, the discharging was not synchronous with electrocortical alpha
      wave activity during AW, delta wave activity during SWS, or gamma wave activity
      during REM. During deprived SWS, there was a direct correlation between increased
      VTA GABA neuron slowing and increased delta wave power. These findings indicate
      that the discharging of VTA GABA neurons correlates with psychomotor behavior and
      that these neurons may be an integral part of the extrathalamic cortical
      activating system.

PMID- 11222666
TI  - Extrinsic modulation and motor pattern generation in a feeding network: a
      cellular study.
AB  - Systems level studies have shown that the paired serotonergic cerebral giant
      cells (CGCs) of gastropod mollusks have important extrinsic modulatory actions on
      the central pattern generator (CPG) underlying rhythmic ingestion movements. Here
      we present the first study that investigates the modulatory actions of the CGCs
      and their released transmitter 5-HT on the CPG at the cellular level. In the
      snail, Lymnaea, motoneurons such as the B4, B8, and B4CL cells are part of the
      feeding CPG and receive serotonergic synaptic inputs from CGCs. These motoneurons
      were used to investigate the effect of serotonergic modulation on endogenous
      cellular properties of CPG neurons. Cells were isolated from the intact nervous
      system, and their properties were examined by pharmacological methods in cell
      culture. Motoneurons were also grown in coculture with CGCs to compare 5-HT
      effects with CGC stimulation. Three distinct modulatory effects of exogenously
      applied 5-HT/CGC activity were seen: all three motoneuron types were depolarized
      by 5-HT for prolonged periods leading to firing. Conditional bursting accompanied
      this depolarization in the B4/B8 cells, but not in B4CL cells. The frequency of
      the bursting was increased with increased CGC tonic firing. An increase in the
      size of postinhibitory rebound (PIR) occurred with 5-HT application in all three
      cell types, because of an increase in a CsCl-sensitive, hyperpolarization
      activated inward current. Similar modulatory effects on membrane potential,
      endogenous bursting, and PIR properties could be observed in the intact nervous
      system and were necessary for motoneuron activation during feeding. Part of the
      systems gating and frequency control functions of the CGCs appear to be caused by
      these modulatory effects on feeding motoneurons.

PMID- 11222667
TI  - Pronociceptive actions of dynorphin maintain chronic neuropathic pain.
AB  - Whereas tissue injury increases spinal dynorphin expression, the functional
      relevance of this upregulation to persistent pain is unknown. Here, mice lacking
      the prodynorphin gene were studied for sensitivity to non-noxious and noxious
      stimuli, before and after induction of experimental neuropathic pain.
      Prodynorphin knock-out (KO) mice had normal responses to acute non-noxious
      stimuli and a mild increased sensitivity to some noxious stimuli. After spinal
      nerve ligation (SNL), both wild-type (WT) and KO mice demonstrated decreased
      thresholds to innocuous mechanical and to noxious thermal stimuli, indicating
      that dynorphin is not required for initiation of neuropathic pain. However,
      whereas neuropathic pain was sustained in WT mice, KO mice showed a return to
      baselines by post-SNL day 10. In WT mice, SNL upregulated lumbar dynorphin
      content on day 10, but not day 2, after injury. Intrathecal dynorphin antiserum
      reversed neuropathic pain in WT mice at post-SNL day 10 (when dynorphin was
      upregulated) but not on post-SNL day 2; intrathecal MK-801 reversed SNL-pain at
      both times. Opioid (mu, delta, and kappa) receptor density and G-protein
      activation were not different between WT and KO mice and were unchanged by SNL
      injury. The observations suggest (1) an early, dynorphin-independent phase of
      neuropathic pain and a later dynorphin-dependent stage, (2) that upregulated
      spinal dynorphin is pronociceptive and required for the maintenance of persistent
      neuropathic pain, and (3) that processes required for the initiation and the
      maintenance of the neuropathic pain state are distinct. Identification of
      mechanisms that maintain neuropathic pain appears important for strategies to
      treat neuropathic pain.

PMID- 11222668
TI  - Dopaminergic role in stimulant-induced wakefulness.
AB  - The role of dopamine in sleep regulation and in mediating the effects of wake
      promoting therapeutics is controversial. In this study, polygraphic recordings
      and caudate microdialysate dopamine measurements in narcoleptic dogs revealed
      that the wake-promoting antinarcoleptic compounds modafinil and amphetamine
      increase extracellular dopamine in a hypocretin receptor 2-independent manner. In
      mice, deletion of the dopamine transporter (DAT) gene reduced non-rapid eye
      movement sleep time and increased wakefulness consolidation independently from
      locomotor effects. DAT knock-out mice were also unresponsive to the normally
      robust wake-promoting action of modafinil, methamphetamine, and the selective DAT
      blocker GBR12909 but were hypersensitive to the wake-promoting effects of
      caffeine. Thus, dopamine transporters play an important role in sleep regulation
      and are necessary for the specific wake-promoting action of amphetamines and
      modafinil.

PMID- 11222669
TI  - Long-range cortical synchronization without concomitant oscillations in the
      somatosensory system of anesthetized cats.
AB  - To determine whether neuronal oscillations are essential for long-range cortical
      synchronization in the somatosensory system, we characterized the incidence and
      response properties of gamma range oscillations (20-80 Hz) among pairs of
      synchronized neurons in primary (SI) and secondary (SII) somatosensory cortex.
      Synchronized SI and SII discharges, which occurred within a 3 msec period, were
      detected in 13% (80 of 621) of single-unit pairs and 25% (29 of 118) of multiunit
      pairs. Power spectra derived from the auto-correlation histograms (ACGs) revealed
      that approximately 15% of the neurons forming synchronized pairs were
      characterized by oscillations. Although 24% of the synchronized neuron pairs
      (19/80) were characterized by oscillations in one or both neurons, only 1% (1/80)
      of these pairs displayed oscillations at the same frequency in both neurons.
      Similar results were observed among pairs of multiunit responses. When single
      trial responses were analyzed, the vast majority of responses still did not
      exhibit oscillations in the gamma frequency range. These results suggest that
      separate populations of cortical neurons can be bound together without being
      constrained by the phase relationships defined by specific oscillatory
      frequencies.

PMID- 11222670
TI  - Pax-6 regulates expression of SFRP-2 and Wnt-7b in the developing CNS.
AB  - Wnt signaling regulates a wide range of developmental processes such as
      proliferation, cell migration, axon guidance, and cell fate determination. In
      this report, we studied the expression of secreted frizzled related protein-2
      (SFRP-2), which codes for a putative Wnt inhibitor, in the developing nervous
      system. SFRP-2 is expressed in several discrete neuroepithelial domains,
      including the diencephalon, the insertion of the eminentia thalami into the
      caudal telencephalon, and the pallial-subpallial boundary (PSB). We also noted
      that Wnt-7b expression was similar to SFRP-2 expression. Because many of these
      structures are disrupted in Pax-6 mutant mice, we examined SFRP-2 and Wnt-7b
      expression in the forebrains of Pax-6 Sey/Sey mice. We found that Pax-6 mutants
      lack SFRP-2 expression in the PSB and diencephalon. Interestingly, Pax-6 mutants
      also lack Wnt-7b expression in the PSB, but Wnt-7b expression in the diencephalon
      is preserved. Furthermore, in the spinal cord of Pax-6 mutants, SFRP-2 and Wnt-7b
      expression was greatly reduced. Our results suggest that by virtue of its
      apposition to Wnt-7b expression, SFRP-2 may modulate its function, particularly
      at boundaries such as the PSB, and that changes in Wnt signaling contribute to
      the phenotype of Pax-6 mutants.

PMID- 11222671
TI  - Previous exposure to amphetamine enhances the subsequent locomotor response to a
      D1 dopamine receptor agonist when glutamate reuptake is inhibited.
AB  - The role of nucleus accumbens (NAcc) glutamate (GLU) and D(1) dopamine (DA)
      receptor activation in the expression of locomotor sensitization to amphetamine
      (AMPH) was investigated in rats. Rats were preexposed to either AMPH or saline,
      and 2 weeks later their locomotion was assessed after a microinjection into the
      NAcc of the selective glutamate reuptake blocker l-trans-pyrrolidine-2,4
      dicarboxylic acid (PDC) (10 nmol per side), the D(1)-like DA receptor agonists
      SKF82958 (2.4 nmol per side) and SKF38393 (3.1 nmol per side), the D(2)-like DA
      receptor agonist quinelorane (3.1 nmol per side), or AMPH (6.8 nmol per side).
      All compounds other than quinelorane increased locomotion when infused into the
      NAcc. Only AMPH, however, produced enhanced locomotion in AMPH relative to saline
      preexposed rats. When additional rats were tested after NAcc infusions of PDC
      together with either SKF82958 or quinelorane, enhanced locomotion was observed in
      AMPH relative to saline-preexposed rats after NAcc PDC + SKF82958. These results
      suggest that in the NAcc, increased GLU neurotransmission and activation of D(1)
      DA receptors, neither of which is by itself sufficient, together contribute to
      the expression of locomotor sensitization by AMPH. They stress, with other
      findings, the importance of GLU-DA interactions in the NAcc not only in the
      generation of acute stimulant drug effects but in sensitized responding to these
      drugs as well.

PMID- 11222672
TI  - Independence of firing correlates of anatomically proximate hippocampal pyramidal
      cells.
AB  - In neocortex, neighboring neurons frequently exhibit correlated encoding
      properties. There is conflicting evidence whether a similar phenomenon occurs in
      hippocampus. To assess this quantitatively, a comparison was made of the spatial
      and temporal firing correlations within and between local groups of hippocampal
      cells, spaced 350-1400 microm apart. No evidence of clustering was found in a
      sample of >3000 neurons. Moreover, cells active in two environments were
      uniformly interspersed at a scale of <100 microm, as assessed by the activity
      induced gene Arc. Independence of encoding characteristics implies uncorrelated
      inputs, which could enhance the capacity of the hippocampus to store arbitrary
      associations.

PMID- 11222673
TI  - Bacteriophage K1-5 encodes two different tail fiber proteins, allowing it to
      infect and replicate on both K1 and K5 strains of Escherichia coli.
AB  - A virulent double-stranded DNA bacteriophage, Phi K1-5, has been isolated and
      found to be capable of infecting Escherichia coli strains that possess either the
      K1 or the K5 polysaccharide capsule. Electron micrographs show that the virion
      consists of a small icosohedral head with short tail spikes, similar to members
      of the Podoviridae family. DNA sequence analysis of the region encoding the tail
      fiber protein showed two open reading frames encoding previously characterized
      hydrolytic phage tail fiber proteins. The first is the K5 lyase protein gene of
      Phi K5, which allows this phage to specifically infect K5 E. coli strains. A
      second open reading frame encodes a protein almost identical in amino acid
      sequence to the N-acetylneuraminidase (endosialidase) protein of Phi K1E, which
      allows this phage to specifically infect K1 strains of E. coli. We provide
      experimental evidence that mature phage particles contain both tail fiber
      proteins, and mutational analysis indicates that each protein can be
      independently inactivated. A comparison of the tail gene regions of Phi K5, Phi
      K1E, and Phi K1-5 shows that the genes are arranged in a modular or cassette
      configuration and suggests that this family of phages can broaden host range by
      horizontal gene transfer.

PMID- 11222674
TI  - Cross-reactive, cell-mediated immunity and protection of chickens from lethal
      H5N1 influenza virus infection in Hong Kong poultry markets.
AB  - In 1997, avian H5N1 influenza virus transmitted from chickens to humans resulted
      in 18 confirmed infections. Despite harboring lethal H5N1 influenza viruses, most
      chickens in the Hong Kong poultry markets showed no disease signs. At this time,
      H9N2 influenza viruses were cocirculating in the markets. We investigated the
      role of H9N2 influenza viruses in protecting chickens from lethal H5N1 influenza
      virus infections. Sera from chickens infected with an H9N2 influenza virus did
      not cross-react with an H5N1 influenza virus in neutralization or
      hemagglutination inhibition assays. Most chickens primed with an H9N2 influenza
      virus 3 to 70 days earlier survived the lethal challenge of an H5N1 influenza
      virus, but infected birds shed H5N1 influenza virus in their feces. Adoptive
      transfer of T lymphocytes or CD8(+) T cells from inbred chickens (B(2)/B(2))
      infected with an H9N2 influenza virus to naive inbred chickens (B(2)/B(2))
      protected them from lethal H5N1 influenza virus. In vitro cytotoxicity assays
      showed that T lymphocytes or CD8(+) T cells from chickens infected with an H9N2
      influenza virus recognized target cells infected with either an H5N1 or H9N2
      influenza virus in a dose-dependent manner. Our findings indicate that cross
      reactive cellular immunity induced by H9N2 influenza viruses protected chickens
      from lethal infection with H5N1 influenza viruses in the Hong Kong markets in
      1997 but permitted virus shedding in the feces. Our findings are the first to
      suggest that cross-reactive cellular immunity can change the outcome of avian
      influenza virus infection in birds in live markets and create a situation for the
      perpetuation of H5N1 influenza viruses.

PMID- 11222675
TI  - Type D retrovirus Gag polyprotein interacts with the cytosolic chaperonin TRiC.
AB  - The carboxy terminus-encoding portion of the gag gene of Mason-Pfizer monkey
      virus (M-PMV), the prototype immunosuppressive primate type D retrovirus, encodes
      a 36-amino-acid, proline-rich protein domain that, in the mature virion, becomes
      the p4 capsid protein. The p4 domain has no known role in M-PMV replication. We
      found that two mutants with premature termination codons that remove half or all
      of the p4 domain produced lower levels of stable Gag protein and of self
      assembled capsids. Interestingly, yeast two-hybrid screening revealed that p4
      specifically interacted with TCP-1gamma, a subunit of the chaperonin TRiC (TCP-1
      ring complex). TRiC is a cytosolic chaperonin that is known to be involved in
      both folding and subunit assembly of a variety of cellular proteins. TCP-1gamma
      also associated with high specificity with the M-PMV pp24/16-p12 domain and human
      immunodeficiency virus p6. Moreover, in cells, Gag polyprotein associated with
      the TRiC chaperonin complex and this association depended on ATP hydrolysis. In
      the p4 truncation mutants, the Gag-TRiC association was significantly reduced.
      These results strongly suggest that cytosolic chaperonin TRiC is involved in Gag
      folding and/or capsid assembly. We propose that TRiC associates transiently with
      nascent M-PMV Gag molecules to assist in their folding. Consequently, properly
      folded Gag molecules carry out the intermolecular interactions involved in self
      assembly of the immature capsid.

PMID- 11222676
TI  - African swine fever virus IAP homologue inhibits caspase activation and promotes
      cell survival in mammalian cells.
AB  - African swine fever virus (ASFV) A224L is a member of the inhibitor of apoptosis
      protein (IAP) family. We have investigated the antiapoptotic function of the
      viral IAP both in stably transfected cells and in ASFV-infected cells. A224L was
      able to substantially inhibit caspase activity and cell death induced by
      treatment with tumor necrosis factor alpha and cycloheximide or staurosporine
      when overexpressed in Vero cells by gene transfection. We have also observed that
      ASFV infection induces caspase activation and apoptosis in Vero cells.
      Furthermore, using a deletion mutant of ASFV lacking the A224L gene, we have
      shown that the viral IAP modulates the proteolytic processing of the effector
      cell death protease caspase-3 and the apoptosis which are induced in the infected
      cells. Our findings indicate that A224L interacts with the proteolytic fragment
      of caspase-3 and inhibits the activity of this protease during ASFV infection.
      These observations could indicate a conserved mechanism of action for ASFV IAP
      and other IAP family members to suppress apoptosis.

PMID- 11222677
TI  - A GP64-null baculovirus pseudotyped with vesicular stomatitis virus G protein.
AB  - The Autographa californica multiple nucleopolyhedrovirus (AcMNPV) GP64 protein is
      an essential virion protein that is involved in both receptor binding and
      membrane fusion during viral entry. Genetic studies have shown that GP64-null
      viruses are unable to move from cell to cell and this results from a defect in
      the assembly and production of budded virions (BV). To further examine
      requirements for virion budding, we asked whether a GP64-null baculovirus, vAc(64
      ), could be pseudotyped by introducing a heterologous viral envelope protein
      (vesicular stomatitis virus G protein [VSV-G]) into its membrane and whether the
      resulting virus was infectious. To address this question, we generated a stably
      transfected insect Sf9 cell line (Sf9(VSV-G)) that inducibly expresses the VSV-G
      protein upon infection with AcMNPV Sf9(VSV-G) and Sf9 cells were infected with
      vAc(64-), and cells were monitored for infection and for movement of infection
      from cell to cell. vAc(64-) formed plaques on Sf9(VSV-G) cells but not on Sf9
      cells, and plaques formed on Sf9(VSV-G) cells were observed only after prolonged
      intervals. Passage and amplification of vAc(64-) on Sf9(VSV-G) cells resulted in
      pseudotyped virus particles that contained the VSV-G protein. Cell-to-cell
      propagation of vAc(64-) in the G-expressing cells was delayed in comparison to
      wild-type (wt) AcMNPV, and growth curves showed that pseudotyped vAc(64-) was
      generated at titers of approximately 10(6) to 10(7) infectious units (IU)/ml,
      compared with titers of approximately 10(8) IU/ml for wt AcMNPV. Propagation and
      amplification of pseudotyped vAc(64-) virions in Sf9(VSV-G) cells suggests that
      the VSV-G protein may either possess the signals necessary for baculovirus BV
      assembly and budding at the cell surface or may otherwise facilitate production
      of infectious baculovirus virions. The functional complementation of GP64-null
      viruses by VSV-G protein was further demonstrated by identification of a vAc(64-)
      derived virus that had acquired the G gene through recombination with Sf9(VSV-G)
      cellular DNA. GP64-null viruses expressing the VSV-G gene were capable of
      productive infection, replication, and propagation in Sf9 cells.

PMID- 11222678
TI  - Duplication of the primary encapsidation and dimer linkage region of human
      immunodeficiency virus type 1 RNA results in the appearance of monomeric RNA in
      virions.
AB  - The dimerization initiation site (DIS) and the dimer linkage sequences (DLS) of
      human immunodeficiency virus type 1 have been shown to mediate in vitro
      dimerization of genomic RNA. However, the precise role of the DIS-DLS region in
      virion assembly and RNA dimerization in virus particles has not been fully
      elucidated, since deletion or mutation of the DIS-DLS region also abolishes the
      packaging ability of genomic RNA. To characterize the DIS-DLS region without
      altering packaging ability, we generated mutant constructs carrying a duplication
      of approximately 1,000 bases including the encapsidation signal and DIS-DLS
      (E/DLS) region. We found that duplication of the E/DLS region resulted in the
      appearance of monomeric RNA in virus particles. No monomers were observed in
      virions of mutants carrying the E/DLS region only at ectopic positions. Monomers
      were not observed when pol or env regions were duplicated, indicating an absolute
      need for two intact E/DLS regions on the same RNA for generating particles with
      monomeric RNA. These monomeric RNAs were most likely generated by intramolecular
      interaction between two E/DLS regions on one genome. Moreover, incomplete genome
      dimerization did not affect RNA packaging and virion formation. Examination of
      intramolecular interaction between E/DLS regions could be a convenient tool for
      characterizing the E/DLS region in virion assembly and RNA dimerization within
      virus particles.

PMID- 11222679
TI  - Nuclear localization and shuttling of herpes simplex virus tegument protein
      VP13/14.
AB  - The herpes simplex virus type 1 gene UL47 encodes the tegument proteins referred
      to collectively as VP13/14, which are believed to be differentially modified
      forms of the same protein. Here we show that the major product of the UL47 gene
      during transient expression is VP14, suggesting that some feature of virus
      infection is required to produce VP13. We have tagged VP13/14 with green
      fluorescent protein and have demonstrated that the protein is targeted
      efficiently to the nucleus, where it often localizes in numerous punctate
      domains. Furthermore, we show that removal of the N-terminal 127 residues of the
      protein abrogates nuclear accumulation, and we have identified a 14-amino-acid
      peptide from this region that is sufficient to function as a nuclear targeting
      signal and transport a heterologous protein to the nucleus. This short peptide
      contains two runs of four arginine residues, suggesting that the VP13/14 nuclear
      localization signal may behave in a manner similar to that of the arginine-rich
      nuclear localization signals of the retrovirus transactivator proteins Tat, Rev,
      and Rex. In addition, by using heterokaryon assays, we show that VP13/14 is
      capable of shuttling between the nucleus and cytoplasm of the cell, a property
      that may be attributed to three leucine-rich stretches in the C-terminal half of
      the protein that again bear similarity to the nuclear export signals of Rev and
      Rex. This is the first demonstration of a tegument protein that is specifically
      targeted to the nucleus, a feature which may be relevant both during virus entry,
      when VP13/14 enters the cell as a component of the tegument, and at later times,
      when large amounts of newly synthesized VP13/14 are present within the cell.

PMID- 11222680
TI  - Fluorescent tagging of herpes simplex virus tegument protein VP13/14 in virus
      infection.
AB  - The cellular site of herpesvirus tegument assembly has yet to be defined. We have
      previously used a recombinant herpes simplex virus type 1 expressing a green
      fluorescent protein (GFP)-tagged tegument protein, namely VP22, to show that VP22
      is localized exclusively to the cytoplasm during infection. Here we have
      constructed a similar virus expressing another fluorescent tegument protein, YFP
      VP13/14, and have visualized the intracellular localization of this second
      tegument protein in live infected cells. In contrast to VP22, VP13/14 is targeted
      predominantly to the nuclei of infected cells at both early and late times in
      infection. More specifically, YFP-13/14 localizes initially to the nuclear
      replication compartments and then progresses into intense punctate domains that
      appear at around 12 h postinfection. At even later times this intranuclear
      punctate fluorescence is gradually replaced by perinuclear micropunctate and
      membranous fluorescence. While the vast majority of YFP-13/14 seems to be
      targeted to the nucleus, a minor subpopulation also appears in a vesicular
      pattern in the cytoplasm that closely resembles the pattern previously observed
      for GFP-22. Moreover, at late times weak fluorescence appears at the cell
      periphery and in extracellular virus particles, confirming that YFP-13/14 is
      assembled into virions. This predominantly nuclear targeting of YFP-13/14
      together with the cytoplasmic targeting of VP22 may imply that there are multiple
      sites of tegument protein incorporation along the virus maturation pathway. Thus,
      our YFP-13/14-expressing virus has revealed the complexity of the intracellular
      targeting of VP13/14 and provides a novel insight into the mechanism of tegument,
      and hence virus, assembly.

PMID- 11222681
TI  - Protein-DNA binding and CpG methylation at nucleotide resolution of latency
      associated promoters Qp, Cp, and LMP1p of Epstein-Barr virus.
AB  - Epstein-Barr viral (EBV) latency-associated promoters Qp, Cp, and LMP1p are
      crucial for the regulated expression of the EBNA and LMP transcripts in
      dependence of the latency type. By transient transfection and in vitro binding
      analyses, many promoter elements and transcription factors have previously been
      shown to be involved in the activities of these promoters. However, the latency
      promoters have only partially been examined at the nucleotide level in vivo.
      Therefore, we undertook a comprehensive analysis of in vivo protein binding and
      CpG methylation patterns at these promoters in five representative cell lines and
      correlated the results with the known in vitro binding data and activities of
      these promoters from previous transfection experiments. Promoter activity
      inversely correlated with the methylation state of promoters, although Qp was a
      remarkable exception. Novel protein binding data were obtained for all promoters.
      For Cp, binding correlated well with promoter activity; for LMP1p and Qp, binding
      patterns looked similar regardless of promoter activity.

PMID- 11222682
TI  - Release of virus from lymphoid tissue affects human immunodeficiency virus type 1
      and hepatitis C virus kinetics in the blood.
AB  - Kinetic parameters of human immunodeficiency virus type 1 (HIV-1) and hepatitis C
      virus (HCV) infections have been estimated from plasma virus levels following
      perturbation of the chronically infected (quasi-) steady state. We extend
      previous models by also considering the large pool of virus localized in the
      lymphoid tissue (LT) compartment. The results indicate that the fastest time
      scale of HIV-1 plasma load decay during therapy probably reflects the clearance
      rate of LT virus and not, as previously supposed, the clearance rate of virus in
      plasma. This resolves the discrepancy between the clearance rate estimates during
      therapy and those based on plasma apheresis experiments. In the extended models
      plasma apheresis measurements are indeed expected to reflect the plasma decay
      rate. We can reconcile all current HIV-1 estimates with this model when, on
      average, the clearance rate of virus in plasma is approximately 20 day(-1), that
      of LT virus is approximately 3 day(-1), and the death rate of virus-producing
      cells is approximately 0.5 day(-1). The fast clearance in the LT compartment
      increases current estimates for total daily virus production. Because HCV is
      produced in the liver, we let virus be produced into the blood compartment of our
      model. The results suggest that extending current HCV models with an LT
      compartment is not likely to affect current estimates for kinetic parameters and
      virus production. Estimates for treatment efficacy might be affected, however.

PMID- 11222683
TI  - Human immunodeficiency virus type 1 induces expression of complement factors in
      human astrocytes.
AB  - Since the brain is separated from the blood immune system by a tight barrier, the
      brain-resident complement system may represent a central player in the immune
      defense of this compartment against human immunodeficiency virus (HIV). Chronic
      complement activation, however, may participate in HIV-associated
      neurodegeneration. Since the level of complement factors in the cerebrospinal
      fluid is known to be elevated in AIDS-associated neurological disorders, we
      evaluated the effect of HIV type 1 (HIV-1) on the complement synthesis of brain
      astrocytes. Incubation of different astrocytic cell lines and primary astrocytes
      with HIV-1 induced a marked upregulation of the expression of the complement
      factors C2 and C3. The synthesis of other secreted or membrane-bound complement
      proteins was not found to be altered. The enhancement of C3 production was
      measured both on the mRNA level and as secreted protein in the culture
      supernatants. HIV-1 laboratory strains as well as primary isolates were capable
      of inducing C3 production with varied effectiveness. The usage of viral
      coreceptors by HIV-1 was proved to be a prerequisite for the upregulation of C3
      synthesis, which was modulated by the simultaneous addition of cytokines. The C3
      protein which is secreted after incubation of the cells with HIV was shown to be
      biologically active as it can participate in the complement cascade.

PMID- 11222684
TI  - Identification of residues of the Moloney murine leukemia virus nucleocapsid
      critical for viral DNA synthesis in vivo.
AB  - The nucleocapsid (NC) protein of retroviruses is a small nucleic acid-binding
      protein important in virion assembly and in the encapsidation of the viral RNA
      genome into the virion particle. Multiple single-amino-acid substitutions were
      introduced into the NC of Moloney murine leukemia virus to examine further its
      role in viral replication. Two residues were shown to play important roles in the
      early events of replication. Unlike viruses with previously characterized NC
      mutations, these viruses showed no impairment in the late events of replication.
      Viruses containing the substitutions L21A and K30A expressed the normal
      complement of properly processed viral Gag proteins. Analysis of the RNA content
      of mutant virions revealed normal levels of unspliced and spliced viral RNA, and
      the tRNA(Pro) primer was properly annealed to the primer binding site on the
      viral genome. The virions demonstrated no defect in initiation of reverse
      transcription using the endogenous tRNA primer or in the synthesis of long viral
      DNA products in vitro. Nonetheless, viruses possessing these NC mutations
      demonstrated significant defects in the synthesis and accumulation of viral DNA
      products in vivo.

PMID- 11222685
TI  - Antiviral response in cells containing Stat1 with heterologous transactivation
      domains.
AB  - The STATs (signal transducers and activators of transcription), latent
      cytoplasmic transcription factors, are activated by binding of extracellular
      polypeptides to cell surface receptors. Dimerization, accumulation in the
      nucleus, and transcriptional inductions of specific genes then occur. The COOH
      terminus of the STATs acts as a transcriptional activation domain (TAD). Stat1,
      one of seven mammalian STAT genes, forms a homodimer after activation by gamma
      interferon and induces transcription of a number of genes. These induced genes in
      turn produce the antiviral state. In the present experiments we used a Stat1
      deficient cell line complemented with Stat1 or various fusion constructs in which
      the wild-type Stat1 TAD was replaced by other TADs to test the possibility that a
      specific activating domain was necessary for the induction of the antiviral
      response. We found that a wide variety of TADs with different activation
      potential appended to the Stat1 COOH terminus could substitute for the wild-type
      protein in inducing the antiviral state.

PMID- 11222686
TI  - Modified FGF4 signal peptide inhibits entry of herpes simplex virus type 1.
AB  - Entry of herpes simplex virus type 1 (HSV-1) into host cells occurs through
      fusion of the viral envelope with the plasma membrane and involves complex and
      poorly understood interactions between several viral and cellular proteins. One
      strategy for dissecting the function of this fusion machine is through the use of
      specific inhibitors. We identified a peptide with antiviral activity that blocks
      HSV-1 infection at the entry stage and during cell-to-cell spreading. This
      peptide (called EB for "entry blocker") consists of the FGF4 signal sequence with
      an RRKK tetramer at the amino terminus to improve solubility. The activity of EB
      depends exclusively but not canonically on the signal sequence. Inhibition of
      virus entry (hrR3) and plaque formation (KOS) strongly depend on virus
      concentrations and serum addition, with 50% inhibitory concentrations typically
      ranging from 1 to 10 microM. Blocking preadsorbed virus requires higher EB
      concentrations. Cytotoxic effects (trypan blue exclusion) are first noted at 50
      microM EB in serum-free medium and at > or = 200 microM in the presence of serum.
      EB does not affect gC-dependent mechanisms of virus attachment and does not block
      virus attachment at 4 degrees C. Instead, EB directly interacts with virions and
      inactivates them irreversibly without, however, disrupting their physical
      integrity as judged by electron microscopy. At subvirucidal concentrations, EB
      changes the adhesive properties of virions, causing aggregation at high virus
      concentrations. This peptide may be a useful tool for studying viral entry
      mechanisms.

PMID- 11222687
TI  - cis-Acting signals in encapsidation of Hantaan virus S-segment viral genomic RNA
      by its N protein.
AB  - The nucleocapsid (N) protein encapsidates both viral genomic RNA (vRNA) and the
      antigenomic RNA (cRNA), but not viral mRNA. Previous work has shown that the N
      protein has preference for vRNA, and this suggested the possibility of a cis
      acting signal that could be used to initiate encapsidation for the S segment. To
      map the cis-acting determinants, several deletion RNA derivatives and synthetic
      oligoribonucleotides were constructed from the S segment of the Hantaan virus
      (HTNV) vRNA. N protein-RNA interactions were examined by UV cross-linking
      studies, filter-binding assays, and gel electrophoresis mobility shift assays to
      define the ability of each to bind HTNV N protein. The 5' end of the S-segment
      vRNA was observed to be necessary and sufficient for the binding reaction.
      Modeling of the 5' end of the vRNA revealed a possible stem-loop structure (SL)
      with a large single-stranded loop. We suggest that a specific interaction occurs
      between the N protein and sequences within this region to initiate encapsidation
      of the vRNAs.

PMID- 11222688
TI  - Ross River virus glycoprotein-pseudotyped retroviruses and stable cell lines for
      their production.
AB  - Pseudotyped retroviruses have important applications as vectors for gene transfer
      and gene therapy and as tools for the study of viral glycoprotein function.
      Recombinant Moloney murine leukemia virus (Mo-MuLV)-based retrovirus particles
      efficiently incorporate the glycoproteins of the alphavirus Ross River virus
      (RRV) and utilize them for entry into cells. Stable cell lines that produce the
      RRV glycoprotein-pseudotyped retroviruses for prolonged periods of time have been
      constructed. The pseudotyped viruses have a broadened host range, can be
      concentrated to high titer, and mediate stable transduction of genes into cells.
      The RRV glycoprotein-pseudotyped retroviruses and the cells that produce them
      have been employed to demonstrate that RRV glycoprotein-mediated viral entry
      occurs through endocytosis and that membrane fusion requires acidic pH.
      Alphavirus glycoprotein-pseudotyped retroviruses have significant advantages as
      reagents for the study of the biochemistry and prevention of alphavirus entry and
      as preferred vectors for stable gene transfer and gene therapy protocols.

PMID- 11222689
TI  - Protection from Ebola virus mediated by cytotoxic T lymphocytes specific for the
      viral nucleoprotein.
AB  - Cytotoxic T lymphocytes (CTLs) are proposed to be critical for protection from
      intracellular pathogens such as Ebola virus. However, there have been no
      demonstrations that protection against Ebola virus is mediated by Ebola virus
      specific CTLs. Here, we report that C57BL/6 mice vaccinated with Venezuelan
      equine encephalitis virus replicons encoding the Ebola virus nucleoprotein (NP)
      survived lethal challenge with Ebola virus. Vaccination induced both antibodies
      to the NP and a major histocompatibility complex class I-restricted CTL response
      to an 11-amino-acid sequence in the amino-terminal portion of the Ebola virus NP.
      Passive transfer of polyclonal NP-specific antiserum did not protect recipient
      mice. In contrast, adoptive transfer of CTLs specific for the Ebola virus NP
      protected unvaccinated mice from lethal Ebola virus challenge. The protective
      CTLs were CD8(+), restricted to the D(b) class I molecule, and recognized an
      epitope within amino acids 43 to 53 (VYQVNNLEEIC) in the Ebola virus NP. The
      demonstration that CTLs can prevent lethal Ebola virus infection affects vaccine
      development in that protective cellular immune responses may be required for
      optimal protection from Ebola virus.

PMID- 11222690
TI  - Increased expression of MIP-1 alpha and MIP-1 beta mRNAs in the brain correlates
      spatially and temporally with the spongiform neurodegeneration induced by a
      murine oncornavirus.
AB  - The chimeric murine oncornavirus FrCas(E) causes a rapidly progressive paralytic
      disease associated with spongiform neurodegeneration throughout the neuroaxis.
      Neurovirulence is determined by the sequence of the viral envelope gene and by
      the capacity of the virus to infect microglia. The neurocytopathic effect of this
      virus appears to be indirect, since the cells which degenerate are not infected.
      In the present study we have examined the possible role of inflammatory responses
      in this disease and have used as a control the virus F43. F43 is an highly
      neuroinvasive but avirulent virus which differs from FrCas(E) only in 3' pol and
      env sequences. Like FrCas(E), F43 infects large numbers of microglial cells, but
      it does not induce spongiform neurodegeneration. RNAase protection assays were
      used to detect differential expression of genes encoding a variety of cytokines,
      chemokines, and inflammatory cell-specific markers. Tumor necrosis factor alpha
      (TNF-alpha) and TNF-beta mRNAs were upregulated in advanced stages of disease but
      not early, even in regions with prominent spongiosis. Surprisingly there was no
      evidence for upregulation of the cytokines interleukin-1 alpha (IL-1 alpha), IL-1
      beta, and IL-6 or of the microglial marker F4/80 at any stage of this disease. In
      contrast, increased levels of the beta-chemokines MIP-1 alpha and -beta were seen
      early in the disease and were concentrated in regions of the brain rich in
      spongiosis, and the magnitude of responses was similar to that observed in the
      brains of mice injected with the glutamatergic neurotoxin ibotenic acid. MIP
      1alpha and MIP-1beta mRNAs were also upregulated in F43-inoculated mice, but the
      responses were three- to fivefold lower and occurred later in the course of
      infection than was observed in FrCas(E)-inoculated mice. These results suggest
      that the robust increase in expression of MIP-1 alpha and MIP-1 beta in the brain
      represents a correlate of neurovirulence in this disease, whereas the TNF
      responses are likely secondary events.

PMID- 11222691
TI  - Role for human immunodeficiency virus type 1 Tat protein in suppression of viral
      reverse transcriptase activity during late stages of viral replication.
AB  - We have examined the role of the human immunodeficiency virus type 1 (HIV-1) Tat
      protein in the regulation of reverse transcription. We show that a two-exon but
      not a one-exon form of Tat markedly suppressed cell-free reverse transcriptase
      (RT) activity. Conversely, viruses expressing two-exon Tat (pNL43 and pNL101)
      showed rapid replication kinetics and more efficient endogenous RT activity
      compared with viruses expressing one-exon Tat (pM1ex). The pM1ex virions, as well
      as pM1ex-infected cells, also contained higher levels of viral DNA than did
      either the pNL43 or pNL101 viruses, indicating that reverse transcription might
      have continued during later stages of viral replication in the absence of the
      second Tat exon. Moreover, degradation of viral genomic RNA was more apparent in
      the pM1ex virions. Accordingly, we propose that the two-exon Tat may help augment
      viral infectivity by suppressing the reverse transcription reaction during late
      stages of viral synthesis and by preventing the synthesis of potentially
      deleterious viral DNA products.

PMID- 11222692
TI  - Inhibition of hepatitis B virus replication by the interferon-inducible MxA
      protein.
AB  - Human MxA is an alpha/beta interferon-inducible intracytoplasmic protein that
      mediates antiviral activity against several RNA viruses. We had previously shown
      that overexpression of the hepatitis B virus (HBV) capsid led to selective
      downregulation of MxA gene expression, suggesting a mechanism by which the virus
      escapes from the host defense system (O. Rosmorduc, H. Sirma, P. Soussan, E.
      Gordien, P. Lebon, M. Horisberger, C. Brechot and D. Kremsdorf, J. Gen. Virol.
      80:1253-1262, 1999). In the present study, we investigated the antiviral activity
      of MxA protein against HBV. MxA-expressing HuH7 clones were established and
      transiently transfected with HBV, and viral replication was then studied. Viral
      protein secretion was profoundly reduced in MxA-expressing clones by 80% for HBV
      surface antigen (HBsAg) and 70% for HBV e antigen (HBeAg). The levels of
      intracytoplasmic HBsAg and HBeAg were reduced by about 80 and 50% in the two MxA
      positive clones tested. A nearly complete disappearance of HBV DNA replicative
      intermediates was observed in MxA-expressing clones. Although the expression of
      total viral RNAs was not modified, two- to fourfold reductions in HBV cytoplasmic
      RNAs were found in MxA-expressing clones. This suggests the inhibition of HBV
      replication at a posttranscriptional level. Indeed, using the well-characterized
      posttranscriptional regulation element (PRE) reporter system, we were able to
      demonstrate a marked reduction (three- to eightfold) in the nucleocytoplasmic
      export of unspliced RNA in MxA-expressing clones. In addition, MxA protein did
      not interact with HBV nucleocapsid or interfere with HBV nucleocapsid formation.
      Our results show an antiviral effect of MxA protein on a DNA virus for the first
      time. MxA protein acts, at least in part, by inhibiting the nucleocytoplasmic
      export of viral mRNA via the PRE sequence.

PMID- 11222693
TI  - Random, asynchronous, and asymmetric transcriptional activity of enhancer
      flanking major immediate-early genes ie1/3 and ie2 during murine cytomegalovirus
      latency in the lungs.
AB  - The lungs are a major organ site of cytomegalovirus (CMV) pathogenesis, latency,
      and recurrence. Previous work on murine CMV latency has documented a high load
      and an even distribution of viral genomes in the lungs after the resolution of
      productive infection. Initiation of the productive cycle requires expression of
      the ie1/3 transcription unit, which is driven by the immediate-early (IE)
      promoter P(1/3) and generates IE1 and IE3 transcripts by differential splicing.
      Latency is molecularly defined by the absence of IE3 transcripts specifying the
      essential transactivator protein IE3. In contrast, IE1 transcripts were found to
      be generated focally and randomly, reflecting sporadic P(1/3) activity. Selective
      generation of IE1 transcripts implies molecular control of latency operating
      after ie1/3 transcription initiation. P(1/3) is regulated by an upstream
      enhancer. It is widely assumed that the viral transcriptional program is started
      by activation of the enhancer through the binding of transcription factors.
      Accordingly, stochastic transcription during latency might reflect episodes of
      enhancer activation by the "noise" activity of intrinsic transcription factors.
      In addition to ie1/3, the enhancer controls gene ie2, which has its own promoter,
      P(2), and is transcribed in opposite direction. We show here that ie2 is also
      randomly transcribed during latency. Notably, however, ie1 and ie2 were found to
      be expressed independently. We infer from this finding that expression of the
      major IE genes is regulated asymmetrically and asynchronously via the combined
      control unit P(1/3) -E-P(2). Our data are consistent with a stochastic nature of
      enhancer action as it is proposed by the "binary" or probability model.

PMID- 11222694
TI  - Macrophage tropism of human immunodeficiency virus type 1 facilitates in vivo
      escape from cytotoxic T-lymphocyte pressure.
AB  - Early after seroconversion, macrophage-tropic human immunodeficiency virus type 1
      (HIV-1) variants are predominantly found, even when a mixture of macrophage
      tropic and non-macrophage-tropic variants was transmitted. For virus contracted
      by sexual transmission, this is presently explained by selection at the port of
      entry, where macrophages are infected and T cells are relatively rare. Here we
      explore an additional mechanism to explain the selection of macrophage-tropic
      variants in cases where the mucosa is bypassed during transmission, such as blood
      transfusion, needle-stick accidents, or intravenous drug abuse. With molecularly
      cloned primary isolates of HIV-1 in irradiated mice that had been reconstituted
      with a high dose of human peripheral blood mononuclear cells, we found that a
      macrophage-tropic HIV-1 clone escaped more efficiently from specific cytotoxic T
      lymphocyte (CTL) pressure than its non-macrophage-tropic counterpart. We propose
      that CTLs favor the selective outgrowth of macrophage-tropic HIV-1 variants
      because infected macrophages are less susceptible to CTL activity than infected T
      cells.

PMID- 11222695
TI  - Herpes simplex virus type 1 blocks the apoptotic host cell defense mechanisms
      that target Bcl-2 and manipulates activation of p38 mitogen-activated protein
      kinase to improve viral replication.
AB  - Wild-type (wt) herpes simplex virus type 1 (HSV-1) suppresses cell death. We
      investigated the apoptotic pathways triggered during infection with mutant
      viruses tsk and 27lacZ (which lack functional ICP4 and ICP27 viral proteins,
      respectively) and examined the mechanisms used by wt HSV-1 to protect against
      programmed cell death induced by the DNA-damaging compound cisplatin. In our
      studies, we used BHK and HeLa cells, with similar results. We suggest that a
      decrease in the levels of Bcl-2 protein is a key event during apoptosis induced
      by the mutant viruses and that Bcl-2 levels are targeted by (i) a decrease of bcl
      2 RNA, (ii) caspase-related proteolysis, and (iii) p38 mitogen-activated protein
      kinase (p38MAPK)-dependent destabilization of Bcl-2 protein. We show that wt HSV
      1, but not the mutant viruses, maintains bcl-2 RNA and protein levels during
      infection and protects from the cisplatin-induced decrease in bcl-2 RNA; our data
      suggest that both ICP27 and ICP4 are required for this function. Additionally, wt
      HSV-1 evades but does not actively block activation of caspases. Although wt HSV
      1 induces p38MAPK activation during infection, it prevents p38MAPK-dependent
      destabilization of Bcl-2 and exploits p38MAPK stimulation to enhance
      transcription of specific viral gene promoters to increase viral yields.

PMID- 11222696
TI  - Evolutionary relationships among parvoviruses: virus-host coevolution among
      autonomous primate parvoviruses and links between adeno-associated and avian
      parvoviruses.
AB  - The current classification of parvoviruses is based on virus host range and
      helper virus dependence, while little data on evolutionary relationships among
      viruses are available. We identified and analyzed 472 sequences of parvoviruses,
      among which there were (virtually) full-length genomes of all 41 viruses
      currently recognized as individual species within the family Parvoviridae. Our
      phylogenetic analysis of full-length genomes as well as open reading frames
      distinguished three evolutionary groups of parvoviruses from vertebrates: (i) the
      human helper-dependent adeno-associated virus (AAV) serotypes 1 to 6 and the
      autonomous avian parvoviruses; (ii) the bovine, chipmunk, and autonomous primate
      parvoviruses, including human viruses B19 and V9; and (iii) the parvoviruses from
      rodents (except for chipmunks), carnivores, and pigs. Each of these three
      evolutionary groups could be further subdivided, reflecting both virus-host
      coevolution and multiple cross-species transmissions in the evolutionary history
      of parvoviruses. No parvoviruses from invertebrates clustered with vertebrate
      parvoviruses. Our analysis provided evidence for negative selection among
      parvoviruses, the independent evolution of their genes, and recombination among
      parvoviruses from rodents. The topology of the phylogenetic tree of autonomous
      human and simian parvoviruses matched exactly the topology of the primate family
      tree, as based on the analysis of primate mitochondrial DNA. Viruses belonging to
      the AAV group were not evolutionarily linked to other primate parvoviruses but
      were linked to the parvoviruses of birds. The two lineages of human parvoviruses
      may have resulted from independent ancient zoonotic infections. Our results
      provide an argument for reclassification of Parvovirinae based on evolutionary
      relationships among viruses.

PMID- 11222697
TI  - Antibody binding and neutralization of primary and T-cell line-adapted isolates
      of human immunodeficiency virus type 1.
AB  - The relative resistance of human immunodeficiency virus type 1 (HIV-1) primary
      isolates (PIs) to neutralization by a wide range of antibodies remains a
      theoretical and practical barrier to the development of an effective HIV vaccine.
      One model to account for the differential neutralization sensitivity between Pls
      and laboratory (or T-cell line-adapted [TCLA]) strains of HIV suggests that the
      envelope protein (Env) complex is made more accessible to antibody binding as a
      consequence of adaptation to growth in established cell lines. Here, we revisit
      this question using genetically related PI and TCLA viruses and molecularly
      cloned env genes. By using complementary techniques of flow cytometry and virion
      binding assays, we show that monoclonal antibodies targeting the V3 loop, CD4
      binding site, CD4-induced determinant of gp120, or the ectodomain of gp41 bind
      equally well to PI and TCLA Env complexes, despite large differences in
      neutralization outcome. The data suggest that the differential neutralization
      sensitivity of PI and TCLA viruses may derive not from differences in the initial
      antibody binding event but rather from differences in the subsequent functioning
      of the PI and TCLA Envs during virus entry. An understanding of these as yet
      undefined differences may enhance our ability to generate broadly neutralizing
      HIV vaccine immunogens.

PMID- 11222698
TI  - Characterization of Rous sarcoma virus Gag particles assembled in vitro.
AB  - Purified retrovirus Gag proteins or Gag protein fragments are able to assemble
      into virus-like particles (VLPs) in vitro in the presence of RNA. We have
      examined the role of nucleic acid and of the NC domain in assembly of VLPs from a
      Rous sarcoma virus (RSV) Gag protein and have characterized these VLPs using
      transmission electron microscopy (TEM), scanning TEM (STEM), and cryoelectron
      microscopy (cryo-EM). RNAs of diverse sizes, single-stranded DNA oligonucleotides
      as small as 22 nucleotides, double-stranded DNA, and heparin all promoted
      efficient assembly. The percentages of nucleic acid by mass, in the VLPs varied
      from 5 to 8%. The mean mass of VLPs, as determined by STEM, was 6.5 x 10(7) Da
      for both RNA-containing and DNA oligonucleotide-containing particles,
      corresponding to a stoichiometry of about 1,200 protein molecules per VLP,
      slightly lower than the 1,500 Gag molecules estimated previously for infectious
      RSV. By cryo-EM, the VLPs showed the characteristic morphology of immature
      retroviruses, with discernible regions of high density corresponding to the two
      domains of the CA protein. In spherically averaged density distributions, the
      mean radial distance to the density corresponding to the C-terminal domain of CA
      was 33 nm, considerably smaller than that of equivalent human immunodeficiency
      virus type 1 particles. Deletions of the distal portion of NC, including the
      second Zn-binding motif, had little effect on assembly, but deletions including
      the charged residues between the two Zn-binding motifs abrogated assembly.
      Mutation of the cysteine and histidine residues in the first Zn-binding motif to
      alanine did not affect assembly, but mutation of the basic residues between the
      two Zn-binding motifs, or of the basic residues in the N-terminal portion of NC,
      abrogated assembly. Together, these findings establish VLPs as a good model for
      immature virions and establish a foundation for dissection of the interactions
      that lead to assembly.

PMID- 11222699
TI  - Identification of novel porcine endogenous betaretrovirus sequences in miniature
      swine.
AB  - PCR amplification of genomic DNA from miniature swine peripheral blood
      lymphocytes, using primers corresponding to highly conserved regions of the
      polymerase (pol) gene, allowed the identification of two novel porcine endogenous
      retrovirus (PERV) sequences, PMSN-1 and PMSN-4. Phylogenetic analyses of the
      nucleotide sequences of PMSN-1 and PMSN-4 revealed them to be most closely
      related to betaretroviruses. The identification of PERVs belonging to the
      Betaretrovirus genus shows that endogenous retroviruses of this family are more
      broadly represented in mammalian species than previously appreciated. Both
      sequences contained inactivating mutations, implying that these particular loci
      are defective. However, Southern blot analysis showed additional copies of
      closely related proviruses in the miniature swine genome. Analyses of fetal and
      adult miniature swine tissues revealed a broad mRNA expression pattern of both
      PMSN-1 and PMSN-4. The most abundant expression was detected in whole bone marrow
      c-kit(+) (CD117(+)) progenitor bone marrow cells, fetal liver, salivary gland,
      and thymus. It appears unlikely that functional loci encoding these novel PERV
      sequences exist, but this remains to be established. The betaretrovirus sequences
      described in this report will allow such investigations to be actively pursued.

PMID- 11222700
TI  - Multiple groups of novel retroviral genomes in pigs and related species.
AB  - In view of the concern over potential infection hazards in the use of porcine
      tissues and organs for xenotransplantation to humans, we investigated the
      diversity of porcine endogenous retrovirus (PERV) genomes in the DNA of domestic
      pigs and related species. In addition to the three known envelope subgroups of
      infectious gamma retroviruses (PERV-A, -B, and -C), classed together here as PERV
      group gamma 1, four novel groups of gamma retrovirus (gamma 2 to gamma 5) and
      four novel groups of beta retrovirus (beta 1 to beta 4) genomes were detected in
      pig DNA using generic and specific PCR primers. PCR quantification indicated that
      the retroviral genome copy number in the Landrace x Duroc F(1) hybrid pig ranged
      from 2 (beta 2 and gamma 5) to approximately 50 (gamma 1). The gamma 1, gamma 2,
      and beta 4 genomes were transcribed into RNA in adult kidney tissue. Apart from
      gamma 1, the retroviral genomes are not known to be infectious, and sequencing of
      a small number of amplified genome fragments revealed stop codons in putative
      open reading frames in several cases. Analysis of DNA from wild boar and other
      species of Old World pigs (Suidae) and New World peccaries (Tayassuidae) showed
      that one retrovirus group, beta 2, was common to all species tested, while the
      others were present among all Old World species but absent from New World
      species. The PERV-C subgroup of gamma1 genomes segregated among domestic pigs and
      were absent from two African species (red river hog and warthog). Thus domestic
      swine and their phylogenetic relatives harbor multiple groups of hitherto
      undescribed PERV genomes.

PMID- 11222701
TI  - Novel, live attenuated simian immunodeficiency virus constructs containing major
      deletions in leader RNA sequences.
AB  - We have constructed a series of simian immunodeficiency virus (SIV) mutants
      containing deletions within a 97-nucleotide (nt) region of the leader sequence.
      Deletions in this region markedly decreased the replication capacity in tissue
      culture, i.e., in both the C8166 and CEMx174 cell lines, as well as in rhesus
      macaque peripheral blood mononuclear cells. In addition, these deletions
      adversely affected the packaging of viral genomic RNA into virions, the
      processing of Gag precursor proteins, and patterns of viral proteins in virions,
      as assessed by biochemical labeling and polyacrylamide gel electrophoresis.
      Different levels of attenuation were achieved by varying the size and position of
      deletions within this 97-nt region, and among a series of constructs that were
      generated, it was possible to rank in vitro virulence relative to that of wild
      type virus. In all of these cases, the most severe impact on viral replication
      was observed when the deletions that were made were located at the 3' rather than
      5' end of the leader region. The potential of viral reversion over protracted
      periods was investigated by repeated viral passage in CEMx174 cells. The results
      showed that several of these constructs showed no signs of reversion after more
      than 6 months in tissue culture. Thus, a series of novel, attenuated SIV
      constructs have been developed that are significantly impaired in replication
      capacity yet retain all viral genes. One of these viruses, termed SD4, may be
      appropriate for study with rhesus macaques, in order to determine whether
      reversions will occur in vivo and to further study this virus as a candidate for
      attenuated vaccination.

PMID- 11222702
TI  - Systemic immunity and mucosal immunity are induced against human immunodeficiency
      virus Gag protein in mice by a new hyperattenuated strain of Listeria
      monocytogenes.
AB  - Vaccines designed to control chronic infections by intracellular agents such as
      human immunodeficiency virus type 1 (HIV-1) require the induction of cell
      mediated immune responses to rid the host of pathogen-infected cells. Listeria
      monocytogenes has characteristics that make it an attractive vaccine vector for
      use against such infections. Here we show that parenteral immunization with a new
      highly attenuated strain of this organism provided complete protection against
      systemic and mucosal challenges with a recombinant vaccinia virus expressing HIV
      1 gag. Immunization also generated a strong, long-term memory cytotoxic-T
      lymphocyte (CTL) response in spleen, mesenteric lymph nodes, and Peyer's patches
      directed against the gag protein. Oral immunization with this attenuated strain
      also produced complete, long-lasting protection against the recombinant virus but
      only against mucosal virus challenge. Curiously, oral immunization was associated
      with a transient CTL response in the three lymphoid tissues examined.

PMID- 11222703
TI  - Variations in disparate regions of the murine coronavirus spike protein impact
      the initiation of membrane fusion.
AB  - The prototype JHM strain of murine hepatitis virus (MHV) is an enveloped, RNA
      containing coronavirus that has been selected in vivo for extreme neurovirulence.
      This virus encodes spike (S) glycoproteins that are extraordinarily effective
      mediators of intercellular membrane fusion, unique in their ability to initiate
      fusion even without prior interaction with the primary MHV receptor, a murine
      carcinoembryonic antigen-related cell adhesion molecule (CEACAM). In considering
      the possible role of this hyperactive membrane fusion activity in neurovirulence,
      we discovered that the growth of JHM in tissue culture selected for variants that
      had lost murine CEACAM-independent fusion activity. Among the collection of
      variants, mutations were identified in regions encoding both the receptor-binding
      (S1) and fusion-inducing (S2) subunits of the spike protein. Each mutation was
      separately introduced into cDNA encoding the prototype JHM spike, and the set of
      cDNAs was expressed using vaccinia virus vectors. The variant spikes were similar
      to that of JHM in their assembly into oligomers, their proteolysis into S1 and S2
      cleavage products, their transport to cell surfaces, and their affinity for a
      soluble form of murine CEACAM. However, these tissue culture-adapted spikes were
      significantly stabilized as S1-S2 heteromers, and their entirely CEACAM-dependent
      fusion activity was delayed or reduced relative to prototype JHM spikes. The
      mutations that we have identified therefore point to regions of the S protein
      that specifically regulate the membrane fusion reaction. We suggest that cultured
      cells, unlike certain in vivo environments, select for S proteins with delayed,
      CEACAM-dependent fusion activities that may increase the likelihood of virus
      internalization prior to the irreversible uncoating process.

PMID- 11222704
TI  - Virus-neutralizing monoclonal antibody expressed in milk of transgenic mice
      provides full protection against virus-induced encephalitis.
AB  - Neutralizing antibodies represent a major host defense mechanism against viral
      infections. In mammals, passive immunity is provided by neutralizing antibodies
      passed to the offspring via the placenta or the milk as immunoglobulin G and
      secreted immunoglobulin A. With the long-term goal of producing virus-resistant
      livestock, we have generated mice carrying transgenes that encode the light and
      heavy chains of an antibody that is able to neutralize the neurotropic JHM strain
      of murine hepatitis virus (MHV-JHM). MHV-JHM causes acute encephalitis and acute
      and chronic demyelination in susceptible strains of mice and rats. Transgene
      expression was targeted to the lactating mammary gland by using the ovine beta
      lactoglobulin promoter. Milk from these transgenic mice contained up to 0.7 mg of
      recombinant antibody/ml. In vitro analysis of milk derived from different
      transgenic lines revealed a linear correlation between antibody expression and
      virus-neutralizing activity, indicating that the recombinant antibody is the
      major determinant of MHV-JHM neutralization in murine milk. Offspring of
      transgenic and control mice were challenged with a lethal dose of MHV-JHM.
      Litters suckling nontransgenic dams succumbed to fatal encephalitis, whereas
      litters suckling transgenic dams were fully protected against challenge,
      irrespective of whether they were transgenic. This demonstrates that a single
      neutralizing antibody expressed in the milk of transgenic mice is sufficient to
      completely protect suckling offspring against MHV-JHM-induced encephalitis.

PMID- 11222705
TI  - In vitro assembly of Sindbis virus core-like particles from cross-linked dimers
      of truncated and mutant capsid proteins.
AB  - A nucleic acid-bound capsid protein dimer was previously identified using a
      Sindbis virus in vitro nucleocapsid assembly system and cross-linking reagents.
      Cross-link mapping, in combination with a model of the nucleocapsid core,
      suggested that this dimer contained one monomer from each of two adjacent
      capsomeres. This intercapsomere dimer is believed to be the initial intermediate
      in the nucleocapsid core assembly mechanism. This paper presents the purification
      of cross-linked dimers of a truncated capsid protein and the partial purification
      of cross-linked dimers of a full-length assembly-defective mutant. The assembly
      of core-like particles from these cross-linked capsid protein dimers is
      demonstrated. Core-like particles generated from cross-linked full-length mutant
      CP(19-264)L52D were examined by electron microscopy and appeared to have a
      morphology similar to that of wild-type in vitro-assembled core-like particles,
      although a slight size difference was often visible. Truncated cross-linked CP(81
      264) dimers generated core-like particles as well. These core-like particles
      could subsequently be disassembled when reversible cross-linking reagents were
      used to form the dimers. The ability of the covalent intercapsomere cross-link to
      rescue capsid proteins with assembly defects or truncations in the amino-terminal
      region of the capsid protein supports the previous model of assembly and suggests
      a possible role for the amino-terminal region of the protein.

PMID- 11222707
TI  - Detection of infectious baboon cytomegalovirus after baboon-to-human liver
      xenotransplantation.
AB  - Xenotransplantation is considered to be a solution for the human donor shortage.
      However, there is a potential risk of transmitting animal infections from the
      transplanted organ. The known transmissibility and clinical significance of human
      cytomegalovirus (HCMV) infection after allotransplantation led us to evaluate
      whether baboon cytomegalovirus (BCMV) transmission could occur after a baboon-to
      human liver xenotransplant. We examined serial blood samples from a baboon liver
      recipient and isolated replication-competent CMV-like agents on days 29, 36, and
      42 after xenotransplantation. BCMV and HCMV DNAs were detected in the day 29
      isolate, while only HCMV DNA was detected in the other isolates. This is the
      first report of detecting a replication-competent virus from a source animal
      after xenotransplantation and is a concern with regard to potential zoonotic
      transmission to others.

PMID- 11222706
TI  - Sequences at the 3' untranslated region of bamboo mosaic potexvirus RNA interact
      with the viral RNA-dependent RNA polymerase.
AB  - The 3' untranslated region (UTR) of bamboo mosaic potexvirus (BaMV) genomic RNA
      was found to fold into a series of stem-loop structures including a pseudoknot
      structure. These structures were demonstrated to be important for viral RNA
      replication and were believed to be recognized by the replicase (C.-P. Cheng and
      C.-H. Tsai, J. Mol. Biol. 288:555-565, 1999). Electrophoretic mobility shift and
      competition assays have now been used to demonstrate that the Escherichia coli
      expressed RNA-dependent RNA polymerase domain (Delta 893) derived from BaMV open
      reading frame 1 could specifically bind to the 3' UTR of BaMV RNA. No competition
      was observed when bovine liver tRNAs or poly(I)(C) double-stranded homopolymers
      were used as competitors, and the cucumber mosaic virus 3' UTR was a less
      efficient competitor. Competition analysis with different regions of the BaMV 3'
      UTR showed that Delta 893 binds to at least two independent RNA binding sites,
      stem-loop D and the poly(A) tail. Footprinting analysis revealed that Delta 893
      could protect the sequences at loop D containing the potexviral conserved hexamer
      motif and part of the stem of domain D from chemical cleavage.

PMID- 11222708
TI  - A novel silencer element in the bovine papillomavirus type 4 promoter represses
      the transcriptional response to papillomavirus E2 protein.
AB  - The long control regions (LCRs) of mucosal epitheliotropic papillomaviruses have
      similar organizations: a promoter region, an enhancer region, and a highly
      conserved distribution of E2 DNA binding sites (C. Desaintes and C. Demeret,
      Semin. Cancer Biol. 7:339--347, 1996). The enhancer of these viruses is
      epithelial cell specific, as it fails to activate transcription from heterologous
      promoters in nonepithelial cell types (B. Gloss, H. U. Bernard, K. Seedorf, and
      G. Klock, EMBO J. 6:3735--3743, 1987). Using the bovine papillomavirus type 4
      (BPV-4) LCR and a bovine primary cell system, we have shown previously that a
      level of epithelial specificity resides in a papillomavirus promoter region. The
      BPV-4 promoter shows an enhanced response to transcriptional activators in
      epithelial cells compared with that of fibroblasts (K. W. Vance, M. S. Campo, and
      I. M. Morgan, J. Biol. Chem. 274:27839--27844, 1999). A chimeric lcr/tk promoter
      suggests that the upstream BPV-4 promoter region determines the cell-type
      selective response of this promoter in fibroblasts and keratinocytes. Promoter
      deletion analysis identified two novel repressor elements that are, at least in
      part, responsible for mediating the differential response of this promoter to
      upstream activators in fibroblasts and keratinocytes. One of these elements,
      promoter repressor element 2 (PRE-2), is conserved in position and sequence in
      the related mucosal epitheliotropic papillomaviruses, BPV-3 and BPV-6. PRE-2
      functions in cis to repress the basal activity of the simian virus 40 promoter
      and binds a specific protein complex. We identify the exact nucleotides necessary
      for binding and correlate loss of binding with loss of transcriptional
      repression. We also incorporate these mutations into the BPV-4 promoter and
      demonstrate an enhanced response of the mutated promoter to E2 in fibroblasts.
      The DNA binding protein in the detected complex is shown to have a molecular mass
      of approximately 50 kDa. The PRE-2 binding protein represents a novel
      transcriptional repressor and regulator of papillomavirus transcription.

PMID- 11222710
TI  - Differences in cytokine and chemokine responses during neurological disease
      induced by polytropic murine retroviruses Map to separate regions of the viral
      envelope gene.
AB  - Infection of the central nervous system (CNS) by several viruses can lead to
      upregulation of proinflammatory cytokines and chemokines. In immunocompetent
      adults, these molecules induce prominent inflammatory infiltrates. However, with
      immunosuppressive retroviruses, such as human immunodeficiency virus (HIV),
      little CNS inflammation is observed yet proinflammatory cytokines and chemokines
      are still upregulated in some patients and may mediate pathogenesis. The present
      study examined expression of cytokines and chemokines in brain tissue of neonatal
      mice infected with virulent (Fr98) and avirulent (Fr54) polytropic murine
      retroviruses. While both viruses infect microglia and endothelia primarily in the
      white matter areas of the CNS, only Fr98 induces clinical CNS disease. The
      pathology consists of gliosis with minimal morphological changes and no
      inflammation, similar to HIV. In the present experiments, mice infected with Fr98
      had increased cerebellar mRNA levels of proinflammatory cytokines tumor necrosis
      factor alpha (TNF-alpha), TNF-beta, and interleukin-1 alpha and chemokines
      macrophage inflammatory protein-1 alpha (MIP-1 alpha), MIP-1 beta, monocyte
      chemoattractant protein 1 (MCP-1), gamma-interferon-inducible protein 10 (IP-10),
      and RANTES compared to mice infected with Fr54 or mock-infected controls. The
      increased expression of these genes occurred prior to the development of clinical
      symptoms, suggesting that these cytokines and chemokines might be involved in
      induction of neuropathogenesis. Two separate regions of the Fr98 envelope gene
      are associated with neurovirulence. CNS disease associated with the N-terminal
      portion of the Fr98 env gene was preceded by upregulation of cytokines and
      chemokines. In contrast, disease associated with the central region of the Fr98
      env gene showed no upregulation of cytokines or chemokines and thus did not
      require increased expression of these genes for disease induction.

PMID- 11222709
TI  - Role of single-stranded DNA binding activity of T antigen in simian virus 40 DNA
      replication.
AB  - We have previously mapped the single-stranded DNA binding domain of large T
      antigen to amino acid residues 259 to 627. By using internal deletion mutants, we
      show that this domain most likely begins after residue 301 and that the region
      between residues 501 and 550 is not required. To study the function of this
      binding activity, a series of single-point substitutions were introduced in this
      domain, and the mutants were tested for their ability to support simian virus 40
      (SV40) replication and to bind to single-stranded DNA. Two replication-defective
      mutants (429DA and 460EA) were grossly impaired in single-stranded DNA binding.
      These two mutants were further tested for other biochemical activities needed for
      viral DNA replication. They bound to origin DNA and formed double hexamers in the
      presence of ATP. Their ability to unwind origin DNA and a helicase substrate was
      severely reduced, although they still had ATPase activity. These results suggest
      that the single-stranded DNA binding activity is involved in DNA unwinding. The
      two mutants were also very defective in structural distortion of origin DNA,
      making it likely that single-stranded DNA binding is also required for this
      process. These data show that single-stranded DNA binding is needed for at least
      two steps during SV40 DNA replication.

PMID- 11222711
TI  - Replicating adenoviruses that target tumors with constitutive activation of the
      wnt signaling pathway.
AB  - Despite important advances in understanding the molecular basis of cancer, few
      treatments have been devised which rationally target known causal oncogenic
      defects. Selectively replicating viruses have a major advantage over
      nonreplicating viruses to target these defects because the therapeutic effect of
      the injected virus is augmented by virus produced within the tumor. To permit
      rational targeting of colon tumors, we have developed replicating adenoviruses
      that express the viral E1B and E2 genes from promoters controlled by the Tcf4
      transcription factor. Tcf4 is constitutively activated by mutations in the
      adenomatous polyposis coli and beta-catenin genes in virtually all colon tumors
      and is constitutively repressed by Groucho and CtBP in normal tissue. The Tcf-E2
      and Tcf-E1B promoters are active in many, but not all, cell lines with activation
      of the wnt pathway. Viruses with Tcf regulation of E2 expression replicate
      normally in SW480 colon cancer cells but show a 50- to 100-fold decrease in
      replication in H1299 lung cancer cells and WI38 normal fibroblasts. Activation of
      wnt signaling by transduction of a stable beta-catenin mutant into normal
      fibroblasts renders the cells permissive for virus replication. Insertion of Tcf4
      sites in the E1B promoter has only small effects on replication in vitro but
      significantly reduces the inflammatory response in a rodent lung model in vivo.
      Replicating adenoviruses with Tcf regulation of both E1B and E2 transcription are
      potentially useful for the treatment of liver metastases from colorectal tumors,
      but additional changes will be required to produce a virus that can be used to
      treat all colon tumors.

PMID- 11222712
TI  - Lytic replication of Kaposi's sarcoma-associated herpesvirus results in the
      formation of multiple capsid species: isolation and molecular characterization of
      A, B, and C capsids from a gammaherpesvirus.
AB  - Despite the discovery of Epstein-Barr virus more than 35 years ago, a thorough
      understanding of gammaherpesvirus capsid composition and structure has remained
      elusive. We approached this problem by purifying capsids from Kaposi's sarcoma
      associated herpesvirus (KSHV), the only other known human gammaherpesvirus. The
      results from our biochemical and imaging analyses demonstrate that KSHV capsids
      possess a typical herpesvirus icosahedral capsid shell composed of four
      structural proteins. The hexameric and pentameric capsomers are composed of the
      major capsid protein (MCP) encoded by open reading frame 25. The heterotrimeric
      complexes, forming the capsid floor between the hexons and pentons, are each
      composed of one molecule of ORF62 and two molecules of ORF26. Each of these
      proteins has significant amino acid sequence homology to capsid proteins in alpha
      and betaherpesviruses. In contrast, the fourth protein, ORF65, lacks significant
      sequence homology to its structural counterparts from the other subfamilies.
      Nevertheless, this small, basic, and highly antigenic protein decorates the
      surface of the capsids, as does, for example, the even smaller basic capsid
      protein VP26 of herpes simplex virus type 1. We have also found that, as with the
      alpha- and betaherpesviruses, lytic replication of KSHV leads to the formation of
      at least three capsid species, A, B, and C, with masses of approximately 200,
      230, and 300 MDa, respectively. A capsids are empty, B capsids contain an inner
      array of a fifth structural protein, ORF17.5, and C capsids contain the viral
      genome.

PMID- 11222713
TI  - Capsid structure of Kaposi's sarcoma-associated herpesvirus, a gammaherpesvirus,
      compared to those of an alphaherpesvirus, herpes simplex virus type 1, and a
      betaherpesvirus, cytomegalovirus.
AB  - The capsid of Kaposi's sarcoma-associated herpesvirus (KSHV) was visualized at 24
      A resolution by cryoelectron microscopy. Despite limited sequence similarity
      between corresponding capsid proteins, KSHV has the same T=16 triangulation
      number and much the same capsid architecture as herpes simplex virus (HSV) and
      cytomegalovirus (CMV). Its capsomers are hexamers and pentamers of the major
      capsid protein, forming a shell with a flat, close-packed, inner surface (the
      "floor") and chimney-like external protrusions. Overlying the floor at trigonal
      positions are (alpha beta(2)) heterotrimers called triplexes. The floor structure
      is well conserved over all three viruses, and the most variable capsid features
      reside on the outer surface, i.e., in the shapes of the protrusions and
      triplexes, in which KSHV resembles CMV and differs from HSV. Major capsid protein
      sequences from the three subfamilies have some similarity, which is closer
      between KSHV and CMV than between either virus and HSV. The triplex proteins are
      less highly conserved, but sequence analysis identifies relatively conserved
      tracts. In alphaherpesviruses, the alpha-subunit (VP19c in HSV) has a 100-residue
      N-terminal extension and an insertion near the C terminus. The small basic capsid
      protein sequences are highly divergent: whereas the HSV and CMV proteins bind
      only to hexons, difference mapping suggests that the KSHV protein, ORF65, binds
      around the tips of both hexons and pentons.

PMID- 11222714
TI  - Expression of major capsid protein VP-1 in the absence of viral particles in
      thymomas induced by murine polyomavirus.
AB  - Thymomas induced by polyomavirus strain PTA in mice are known to express the
      major capsid protein VP-1. Since the expression of a late structural protein such
      as VP-1 is considered a sign of virus replication, the present work attempted to
      clarify the implication of the presence of this protein in tumor cells. Electron
      microscopy of tumors showed a striking absence of viral particles in the vast
      majority of the cells. However, immunoelectron microscopy of the same samples
      demonstrated intranuclear VP-1 in most cells despite the absence of viral
      particles. Very little infectious virus was recovered from tumors. A change in
      the electrophoretic mobility of VP-1 from thymomas was detected compared with VP
      1 from productively infected cells. The data presented in this work prove that
      the expression of VP-1 in polyomavirus-induced tumors is not synonymous with the
      presence of infectious virus, suggesting a possible defect in viral
      encapsidation.

PMID- 11222715
TI  - Nuclear covalently closed circular viral genomic DNA in the liver of hepatocyte
      nuclear factor 1 alpha-null hepatitis B virus transgenic mice.
AB  - The role of hepatocyte nuclear factor 1alpha (HNF1 alpha) in the regulation of
      hepatitis B virus (HBV) transcription and replication in vivo was investigated
      using a HNF1 alpha-null HBV transgenic mouse model. HBV transcription was not
      measurably affected by the absence of the HNF1 alpha transcription factor.
      However, intracellular viral replication intermediates were increased two- to
      fourfold in mice lacking functional HNF1 alpha protein. The increase in
      encapsidated cytoplasmic replication intermediates in HNF1 alpha-null HBV
      transgenic mice was associated with the appearance of nonencapsidated nuclear
      covalently closed circular (CCC) viral genomic DNA. Viral CCC DNA was not readily
      detected in HNF1 alpha-expressing HBV transgenic mice. This indicates the
      synthesis of nuclear HBV CCC DNA, the proposed viral transcriptional template
      found in natural infection, is regulated either by subtle alterations in the
      levels of viral transcripts or by changes in the physiological state of the
      hepatocyte in this in vivo model of HBV replication.

PMID- 11222716
TI  - Inducible cyclic AMP early repressor produces reactivation of latent herpes
      simplex virus type 1 in neurons in vitro.
AB  - Herpes simplex virus type 1 (HSV-1) establishes a latent infection in neurons of
      the peripheral nervous system. During latent HSV-1 infection, viral gene
      expression is limited to latency-associated transcripts (LAT). HSV-1 remains
      latent until an unknown mechanism induces reactivation. The ability of the latent
      virus to periodically reactivate and be shed is essential to the transmission of
      disease. In vivo, the stimuli that induce reactivation of latent HSV-1 include
      stress, fever, and UV damage to the skin at the site of initial infection. In
      vitro, in primary neurons harboring latent HSV-1, nerve growth factor (NGF)
      deprivation or forskolin treatment induces reactivation. However, the mechanism
      involved in the induction of reactivation remains poorly understood. An in vitro
      neuronal model of HSV-1 latency was used to investigate potential mechanisms
      involved in the induction of reactivation of latent HSV-1. In situ hybridization
      analysis of neuronal cultures harboring latent HSV-1 showed a marked, rapid
      decrease in the percentage of LAT-positive neurons following induction of
      reactivation by NGF deprivation or forskolin treatment. Western blot analysis
      showed a corresponding increase in expression of the cellular transcription
      factor inducible cyclic AMP early repressor (ICER) during reactivation. In
      transient-transfection assays, ICER downregulated LAT promoter activity.
      Expression of ICER from a recombinant adenoviral vector induced reactivation and
      decreased the percentage of LAT-positive neurons in neuronal cultures harboring
      latent HSV-1. These results indicate that ICER represses LAT expression and
      induces reactivation of latent HSV-1.

PMID- 11222717
TI  - Spontaneous activation of the lytic cycle in cells infected with a recombinant
      Kaposi's sarcoma-associated virus.
AB  - The genetic analysis of human herpesvirus 8 (HHV8), also termed Kaposi's sarcoma
      associated virus, has been hampered by severe difficulties in producing
      infectious viral particles and modifying the viral genome. In this article, we
      report the successful cloning of the HHV8 complete genome onto a prokaryotic F
      plasmid replicon which allows the propagation of the recombinant viral DNA in
      Escherichia coli. The insertion of the F-plasmid into the HHV8 genome interrupts
      the ORF56 gene, whose expression product-by homology with the Epstein-Barr virus
      BSLF1 gene--is supposed to be necessary for lytic DNA replication. After
      introduction of the recombinant HHV8 DNA into 293 cells, early viral antigens are
      expressed, suggesting that spontaneous lytic replication is initiated. However,
      completion of the lytic program is prevented by the absence of the ORF56 protein,
      and a quasi-latent state is established. Upon reintroduction of the ORF56 viral
      gene, the block is overcome and infectious HHV8 virions are produced. As the
      recombinant HHV8 genome can be easily modified in E. coli, this experimental
      system opens the way to an extensive genetic analysis of other HHV8 functions.

PMID- 11222718
TI  - Linkage between STAT regulation and Epstein-Barr virus gene expression in tumors.
AB  - Epstein-Barr virus (EBV) latency gene expression in lymphoblastoid cell lines is
      regulated by EBNA2. However, the factors regulating viral expression in EBV
      associated tumors that do not express EBNA2 are poorly understood. In EBV
      associated tumors, EBNA1 and frequently LMP1 are synthesized. We found that an
      alternative latent membrane protein 1 (LMP1) promoter, L1-TR, located within the
      terminal repeats is active in both nasopharyngeal carcinoma and Hodgkin's disease
      tissues. Examination of the L1-TR and the standard ED-L1 LMP1 promoters in
      electrophoretic mobility shift assays revealed that both promoters contain
      functional STAT binding sites. Further, both LMP1 promoters responded in reporter
      assays to activation of JAK-STAT signaling. Cotransfection of JAK1 or v-Src or
      treatment of cells with the cytokine interleukin-6 upregulated expression from ED
      L1 and L1-TR reporter plasmids. Cotransfection of a dominant negative STAT3 beta
      revealed that STAT3 is likely to be the biologically relevant STAT for EBNA1 Qp
      and LMP1 L1-TR promoter regulation. In contrast, LMP1 expression from ED-L1 was
      not abrogated by STAT3 beta, indicating that the two LMP1 promoters are regulated
      by different STAT family members. Taken together with the previous demonstration
      of JAK-STAT activation of Qp driven EBNA1 expression, this places two of the EBV
      genes most commonly expressed in tumors under the control of the same signal
      transduction pathway. Immunohistochemical analyses of nasopharyngeal carcinoma
      tumors revealed that STAT3, STAT5, and STAT1 are constitutively activated in
      these tumors while STAT3 is constitutively activated in the malignant cells of
      Hodgkin's disease. We hypothesize that chronic or aberrant STAT activation may be
      both a necessary and predisposing event for EBV-driven tumorigenesis in
      immunocompetent individuals.

PMID- 11222719
TI  - Internal ribosome entry site regulates translation of Kaposi's sarcoma-associated
      herpesvirus FLICE inhibitory protein.
AB  - The gammaherpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) (or human
      herpesvirus 8) is associated with the endothelial tumor Kaposi's sarcoma (KS) and
      lymphoproliferative disorders in immunocompromised individuals. Only a small
      number of viral proteins are expressed in B cells latently infected with KSHV;
      here we characterize the mechanism of expression of one of these, the viral FLICE
      inhibitory protein v-FLIP (K13, ORF71). The v-FLIP coding region is present in a
      bicistronic message, following the v-cyclin coding region. Using both in vitro
      translation and cell transfection assays, we have identified an internal ribosome
      entry site (IRES) preceding the v-FLIP start codon and overlapping the v-cyclin
      (ORF 72) coding region, which allows v-FLIP translation. Using an antibody
      against v-FLIP we have detected expression of the endogenous protein in latently
      infected KSHV-positive primary effusion lymphoma (PEL) cell lines. Induction of
      apoptosis by serum withdrawal from PEL cells results in a relative increase in v
      FLIP synthesis, as previously described for some cellular proteins translated
      from IRES.

PMID- 11222720
TI  - Epstein-Barr virus BamHi-a rightward transcript-encoded RPMS protein interacts
      with the CBF1-associated corepressor CIR to negatively regulate the activity of
      EBNA2 and NotchIC.
AB  - The Epstein-Barr virus (EBV) BamHI-A rightward transcripts (BARTs) are expressed
      in all EBV-associated tumors as well as in latently infected B cells in vivo and
      cultured B-cell lines. One of the BART family transcripts contains an open
      reading frame, RPMS1, that encodes a nuclear protein termed RPMS. Reverse
      transcription-PCR analysis revealed that BART transcripts with the splicing
      pattern that generates the RPMS1 open reading frame are commonly expressed in EBV
      positive lymphoblastoid cell lines and are also detected in Hodgkin's disease
      tissues. Experiments undertaken to determine the function of RPMS revealed that
      RPMS interacts with both CBF1 and components of the CBF1-associated corepressor
      complex. RPMS interaction with CBF1 was demonstrated in a glutathione S
      transferase (GST) affinity assay and by the ability of RPMS to alter the
      intracellular localization of a mutant CBF1. A Gal4-RPMS fusion protein mediated
      transcriptional repression, suggesting an additional interaction between RPMS and
      corepressor proteins. GST affinity assays revealed interaction between RPMS and
      the corepressor Sin3A and CIR. The RPMS-CIR interaction was further substantiated
      in mammalian two-hybrid, coimmunoprecipitation, and colocalization experiments.
      RPMS has been shown to interfere with NotchIC and EBNA2 activation of CBF1
      containing promoters in reporter assays. Consistent with this function,
      immunofluorescence assays performed on cotransfected cells showed that there was
      colocalization of RPMS with NotchIC and with EBNA2 in intranuclear punctate
      speckles. The effect of RPMS on NotchIC function was further examined in a muscle
      cell differentiation assay where RPMS was found to partially reverse NotchIC
      mediated inhibition of differentiation. The mechanism of RPMS action was examined
      in cotransfection and mammalian two-hybrid assays. The results revealed that RPMS
      blocked relief of CBF1-mediated repression and interfered with SKIP-CIR
      interactions. We conclude that RPMS acts as a negative regulator of EBNA2 and
      Notch activity through its interactions with the CBF1-associated corepressor
      complex.

PMID- 11222722
TI  - Adenovirus type 5 viral particles pseudotyped with mutagenized fiber proteins
      show diminished infectivity of coxsackie B-adenovirus receptor-bearing cells.
AB  - A major limitation of adenovirus type 5 (Ad5)-based gene therapy, the inability
      to target therapeutic genes to selected cell types, is attributable to the
      natural tropism of the virus for the widely expressed coxsackievirus-adenovirus
      receptor (CAR) protein. Modifications of the Ad5 fiber knob domain have been
      shown to alter the tropism of the virus. We have developed a novel system to
      rapidly evaluate the function of modified fiber proteins in their most relevant
      context, the adenoviral capsid. This transient transfection/infection system
      combines transfection of cells with plasmids that express high levels of the
      modified fiber protein and infection with Ad5.beta gal.Delta F, an E1-, E3-, and
      fiber-deleted adenoviral vector encoding beta-galactosidase. We have used this
      system to test the adenoviral transduction efficiency mediated by a panel of
      fiber protein mutants that were proposed to influence CAR interaction. A series
      of amino acid modifications were incorporated via mutagenesis into the fiber
      expression plasmid, and the resulting fiber proteins were subsequently
      incorporated onto adenoviral particles. Mutations located in the fiber knob AB
      and CD loops demonstrated the greatest reduction in fiber-mediated gene transfer
      in HeLa cells. We also observed effects on transduction efficiency with mutations
      in the FG loop, indicating that the binding site may extend to the adjacent
      monomer in the fiber trimer and in the HI loop. These studies support the concept
      that modification of the fiber knob domain to diminish or ablate CAR interaction
      should result in a detargeted adenoviral vector that can be combined
      simultaneously with novel ligands for the development of a systemically
      administered, targeted adenoviral vector.

PMID- 11222721
TI  - Exchange of the basic domain of human immunodeficiency virus type 1 Rev for a
      polyarginine stretch expands the RNA binding specificity, and a minimal arginine
      cluster is required for optimal RRE RNA binding affinity, nuclear accumulation,
      and trans-activation.
AB  - The Rev regulatory protein of human immunodeficiency virus (HIV) facilitates the
      nuclear export of unspliced and partially spliced HIV RNAs. Using a Rev:MS2 phage
      coat protein fusion that could be targeted to bind and activate the Rev
      responsive element (RRE) RNA or heterologous MS2 phage operator RNA, we analyzed
      the role(s) of the arginine-rich RNA binding domain in RNA binding and
      transactivation. The arginine-rich domain could be functionally replaced by a
      stretch of nine arginines. However, polyarginine substitutions expanded the RNA
      binding specificity of the resultant mutant Rev protein. Polyarginine insertions
      in place of residues 24 to 60 that excised the RNA binding and oligomerization
      domains of Rev preserved the activation for MS2 RNA, but not for the RRE. A nine
      arginine insertion outside of the natural context of the Rev nuclear localization
      signal domain was incompatible with activation of either RNA target. Insertions
      of fewer than eight arginines impaired RRE activation. Interrupted lysine
      clusters and disruption of the arginine stretch with lysine or neutral residues
      resulted in a similar phenotype. Some of these mutants with a null phenotype for
      RRE activated the heterologous MS2 RNA target. Under steady-state conditions,
      mutants that preserved the Rev response for RRE RNA localized to the nuclei;
      those with poor or no Rev response accumulated mostly in the cytoplasm. Many of
      the cytoplasmically resident derivatives became nuclear when leptomycin B (LMB)
      treatment inhibited nuclear export of nuclear export signal-containing proteins.
      Mutants that had a null activation potential for either RNA target were
      particularly resistant to LMB treatment. Abbreviated nuclear residence times and
      differences in RRE binding affinity may have compromised their activation
      potential for RRE. High-affinity binding to MS2 RNA through the intact coat
      protein was sufficient to overcome the short nuclear residence times and to
      facilitate MS2 activation by some derivatives.

PMID- 11222723
TI  - The highly conserved C-terminal dileucine motif in the cytosolic domain of the
      human immunodeficiency virus type 1 envelope glycoprotein is critical for its
      association with the AP-1 clathrin adaptor [correction of adapter].
AB  - Short amino acid sequences in the cytosolic domains of transmembrane proteins are
      recognized by specialized adaptor [corrected] proteins which are part of coated
      vesicles utilized to transport membrane proteins between the trans-Golgi network
      (TGN) and the plasma membrane (forward and backward). Previously, we and others
      reported that the membrane-proximal tyrosine residues Y712 (human
      immunodeficiency virus [HIV]) and Y721 (simian immunodeficiency virus [SIV]) in
      the envelope glycoprotein (Env) of the primate lentiviruses are crucial for the
      association of Env with clathrin-associated adaptor [corrected] complex AP-2. The
      same tyrosine-based endocytosis motifs in the cytosolic domains (EnvCD) of
      transmembrane gp41 of HIV type 1 (HIV-1) and SIV, respectively, were also shown
      to modulate the interaction with TGN- and endosome-based clathrin-associated
      complex AP-1. Our findings suggested that EnvCD binding to AP-1, unlike the
      association of EnvCD with AP-2, is dependent largely on residues other than Y712
      and Y721. Here, we tested if motifs downstream of Y712 affect HIV-1 EnvCD-AP-1
      binding and Env trafficking. Mutational analysis revealed that the C-terminal
      leucine-based motif in Env was crucial for the recruitment of AP-1 in vitro and
      in Env-expressing cells. In addition to affecting Env-AP-1 association, mutations
      at the C terminus of Env also altered the subcellular localization of Env,
      suggesting that proper post-Golgi routing of Env depends on its recruitment of AP
      1. Finally, the C-terminal dileucine was shown to assist the membrane-proximal
      Y712 motif in restricting the cell surface expression of Env.

PMID- 11222724
TI  - Human immunodeficiency virus type 1 Nef functions at the level of virus entry by
      enhancing cytoplasmic delivery of virions.
AB  - The Nef protein of the type 1 human immunodeficiency virus (HIV-1) plays a key
      although poorly understood role in accelerating the progression of clinical
      disease in vivo. Nef exerts several biological effects in vitro, including
      enhancement of virion infectivity, downregulation of CD4 and major
      histocompatibility complex class I receptor expression, and modulation of various
      intracellular signaling pathways. The positive effect of Nef on virion
      infectivity requires its expression in the producer cell, although its effect is
      manifested in the subsequent target cell of infection. Prior studies suggest that
      Nef does not alter viral entry into target cells; nevertheless, it enhances
      proviral DNA synthesis, arguing for an action of Nef at the level of viral
      uncoating or reverse transcription. However, these early studies discounting an
      effect of Nef on virion entry may be confounded by the recent finding that HIV
      enters cells by both fusion and endocytosis. Using epifluorescence microscopy to
      monitor green fluorescent protein-Vpr-labeled HIV virion entry into HeLa cells,
      we find that endocytosis forms a very active pathway for virus uptake. Virions
      entering via the endocytic pathway do not support productive infection of the
      host cell, presumably reflecting their inability to escape from the endosomes.
      Conversely, our studies now demonstrate that HIV Nef significantly enhances CD4-
      and chemokine receptor-dependent entry of HIV virions into the cytoplasmic
      compartment of target cells. Mutations in Nef either impairing its ability to
      downregulate CD4 or disrupting its polyproline helix compromise virion entry into
      the cytoplasm. We conclude that Nef acts at least in part as a regulator of
      cytosolic viral entry and that this action contributes to its positive effects on
      viral infectivity.

PMID- 11222725
TI  - Expression of human MxA protein in mosquito cells interferes with LaCrosse virus
      replication.
AB  - Human MxA protein inhibits LaCrosse virus (LAC virus; family Bunyaviridae)
      replication in vertebrate cells and MxA-transgenic mice. LAC virus is transmitted
      to humans by Aedes triseriatus mosquitoes. In this report, we have shown that
      transfected mosquito cells expressing the human MxA cDNA are resistant to LAC
      virus but permissive for Sindbis virus (family Togaviridae) infection.

PMID- 11222726
TI  - Evaluation of accumulation of hepatitis C virus mutations in a chronically
      infected chimpanzee: comparison of the core, E1, HVR1, and NS5b regions.
AB  - Four hepatitis C virus genome regions (the core, E1, HVR1, and NS5b) were
      amplified and sequenced from yearly samples obtained from a chronically infected
      chimpanzee over a 12-year span. Nucleotide substitutions were found to accumulate
      in the core, E1, and HVR1 regions during the course of chronic infection;
      substitutions within the NS5b region were not detected for the first 8 years and
      were found to be minimal during the last 4 years. The rate of accumulation of
      mutations in the core and E1 regions, based on a direct comparison between the
      first 1979 sequence and the last 1990 sequence, was 1.120 x 10(-3), while
      phylogenetic ancestral comparison using the 12 yearly sequences showed a rate of
      0.816 x 10(-3) bases per site per year. Temporal evaluation of the sequences
      revealed that there appeared to be periods in which substitutions accumulated and
      became fixed, followed by periods with relative stasis or random substitutions
      that did not persist. Synonymous and nonsynonymous substitutions within the core,
      E1, and HVR1 regions were also analyzed. In the core and E1 regions, synonymous
      substitutions predominated and gradually increased over time. However, within the
      HVR1 region, nonsynonymous substitutions predominated but gradually decreased
      over time.

PMID- 11222727
TI  - TRADD domain of Epstein-Barr virus transforming protein LMP1 is essential for
      inducing immortalization and suppressing senescence of primary rodent
      fibroblasts.
AB  - Mutation analysis of latent membrane protein 1 (LMP1) in Epstein-Barr virus (EBV)
      induced B-cell immortalization revealed two transformation effector sites, TES1
      and TES2. TES2 mediates the interaction with tumor necrosis factor receptor
      associated death domain protein (TRADD) and plays a key role in transactivating
      NF-kappa B and AP-1. Recombinant EBV containing LMP1 with TES2 deleted induces a
      limited proliferation of B cells. The present study shows that a mutant with an
      LMP1 site-specific mutation at TES2, LMP1(TRADD), initially stimulates cell
      growth and significantly extends the life span of MEF. However, it is not
      sufficient for the immortalization of MEF, and MEF-LMP1(TRADD) cells eventually
      enter growth arrest. Further analysis reveals that although LMP1(TRADD) promotes
      cell growth, it does not prevent the eventual onset of senescence and the
      expression of tumor suppressor p16(Ink4a).

PMID- 11222728
TI  - Establishment of latent Epstein-Barr virus infection and stable episomal
      maintenance in murine B-cell lines.
AB  - Epstein-Barr virus (EBV) is a strict human pathogen for which no small animal
      models exist. Plasmids that contain the EBV plasmid origin of replication, oriP,
      and express EBV nuclear antigen 1 (EBNA1) are stably maintained
      extrachromosomally in human cells, whereas these plasmids replicate poorly in
      rodent cells. However, the ability of oriP and EBNA1 to maintain the entire EBV
      episome in proliferating rodent cells has not been determined. Expression of the
      two human B-cell receptors for EBV on the surfaces of murine B cells allows
      efficient viral entry that leads to the establishment of latent EBV infection and
      long-term persistence of the viral genome. Latent gene expression in these cells
      resembles the latency II profile in that EBNA1 and LMP1 can be detected whereas
      EBNA2 and the EBNA3s are not expressed.

PMID- 11222729
TI  - Downregulation of IRF-3 levels by ribozyme modulates the profile of IFNA subtypes
      expressed in infected human cells.
AB  - As an early response to viral infection, cells express a number of cellular genes
      that play a role in innate immunity, including alpha/beta interferons (IFN). IFN
      alpha/beta are encoded by a single IFNB gene and multiple, closely related IFNA
      genes. The induction of these IFN genes in infected cells occurs at the
      transcriptional level, and two transcription factors of the IRF family, IRF-3 and
      IRF-7, were shown to play a role in their activation. While the expression of IRF
      3 alone was shown to be sufficient for induction of the IFNB gene, induction of
      all the IFNA subtypes in human cells required the presence of IRF-7. Since IRF-3
      is expressed constitutively in all cells examined, the role of IRF-3 in the
      induction of IFNA genes has not been clarified. Using ribozyme targeted to IRF-3
      mRNA, we found that the downregulation of IRF-3 levels in the infected cells
      inhibited not only the induction of IFNB gene but also the expression of IFNA
      genes. Furthermore, downmodulation of IRF-3 levels altered the expression profile
      of IFNA subtypes induced by viral infection. These studies suggest that the ratio
      between the relative levels of IRF-3 and IRF-7 is a critical determinant for the
      induction of the individual IFNA subtypes in infected cells.

PMID- 11222730
TI  - Simian immunodeficiency virus (SIV) infection of a rhesus macaque induces SIV
      specific CD8(+) T cells with a defect in effector function that is reversible on
      extended interleukin-2 incubation.
AB  - A vigorous expansion of antigen-specific CD8(+) T cells lacking apparent effector
      function was observed in a rhesus macaque acutely infected with the simian
      immunodeficiency virus (SIV) strain SIVmac239. Antigen-specific CD8(+) T cells
      were identified using antigenic-peptide class I major histocompatibility complex
      tetramers. As many as 8.3% of CD8(+) cells recognized the Mamu-A*01-associated
      SIV epitope Gag(181-189) (CTPYDINQM); however, these cells demonstrated no
      effector function when presented with peptide-incubated targets, as measured by
      intracellular cytokine staining for gamma interferon (IFN-gamma), interleukin-2
      (IL-2) production, or direct cellular lysis. Similar results were observed with
      three other SIV peptide antigens. Nonresponsiveness did not correlate with
      apoptosis of the CD8(+) cells, nor were cells from this macaque impaired in their
      ability to present peptide antigens. Associated with the nonresponsive state was
      a lack of IL-2 production and decreased IL-2 receptor expression. Exogenous IL-2
      treatment for 1 week in the absence of antigenic stimulation restored antigen
      specific responses and the quantitative correlation between tetramer recognition
      and antigen-responsive IFN-gamma secretion. This case report suggests a
      regulatory mechanism that may impede the effector function of antigen-specific T
      cells during acute infection with SIV or human immunodeficiency virus in some
      cases. This mechanism may participate in the failure of the immune system to
      limit infection.

PMID- 11222731
TI  - Activation of NFAT-dependent gene expression by Nef: conservation among divergent
      Nef alleles, dependence on SH3 binding and membrane association, and cooperation
      with protein kinase C-theta.
AB  - Here we show that the potential to regulate NFAT is a conserved property of
      different Nef alleles and that Nef residues involved in membrane targeting and
      SH3 binding are critical for this function. Cotransfection of an activated
      protein kinase C-theta (PKC-theta) with Nef implicated PKC-theta as a possible
      physiological cofactor of Nef in promoting NFAT-dependent gene expression and T
      cell activation.

PMID- 11222732
TI  - Membrane-anchored peptide inhibits human immunodeficiency virus entry.
AB  - Peptides derived from the heptad repeats of human immunodeficiency virus (HIV)
      gp41 envelope glycoprotein, such as T20, can efficiently inhibit HIV type 1 (HIV
      1) entry. In this study, replication of HIV-1 was inhibited more than 100-fold in
      a T-helper cell line transduced with a retrovirus vector expressing membrane
      anchored T20 on the cell surface. Inhibition was independent of coreceptor usage.

PMID- 11222733
TI  - High-magnitude, virus-specific CD4 T-cell response in the central nervous system
      of coronavirus-infected mice.
AB  - The neurotropic JHM strain of mouse hepatitis virus (MHV) causes acute
      encephalitis and chronic demyelinating encephalomyelitis in rodents. Previous
      results indicated that CD8 T cells infiltrating the central nervous system (CNS)
      were largely antigen specific in both diseases. Herein we show that by 7 days
      postinoculation, nearly 30% of the CD4 T cells in the acutely infected CNS were
      MHV specific by using intracellular gamma interferon (IFN-gamma) staining assays.
      In mice with chronic demyelination, 10 to 15% of the CD4 T cells secreted IFN
      gamma in response to MHV-specific peptides. Thus, these results show that
      infection of the CNS is characterized by a large influx of CD4 T cells specific
      for MHV and that these cells remain functional, as measured by cytokine
      secretion, in mice with chronic demyelination.

PMID- 11222735
TI  - Discovery of a novel murine type C retrovirus by data mining.
AB  - Analysis of genomic and expression data allows both identification and
      characterization of novel retroviruses. We describe a recombinant type C murine
      retrovirus, similar to the Mus dunni endogenous retrovirus, with VL30-like long
      terminal repeats and murine leukemia virus-like coding sequences. This virus is
      present in multiple copies in the mouse genome and expressed in a range of mouse
      tissues.

PMID- 11222734
TI  - Gender influences herpes simplex virus type 1 infection in normal and gamma
      interferon-mutant mice.
AB  - Gender influences the incidence and severity of some bacterial and viral
      infections and autoimmune diseases in animal models and humans. To determine a
      gender-based difference, comparisons were made between male and female mice
      inoculated with herpes simplex virus type 1 (HSV-1) by the corneal route.
      Mortality was higher in the male mice of the three strains tested: 129/Sv//Ev
      wild type, gamma interferon (IFN-gamma) knockout (GKO), and IFN-gamma receptor
      knockout (RGKO). Similarly, in vivo HSV-1 reactivation occurred more commonly in
      male mice, but the male-female difference in reactivation was restricted to the
      two knockout strains and was not seen in the 129/Sv//Ev control. Comparison among
      male mice of the three strains showed a higher mortality of the RGKO mice and a
      higher reactivation rate of the GKO and RGKO mice than of the 129/Sv//Ev males.
      In contrast, female RGKO and GKO mice did not differ from female 129/Sv//Ev
      controls in either mortality or reactivation. HSV-1 periocular and eyelid disease
      was also more severe in male and dihydrotestosterone (DHT)-treated female mice
      than in control female mice. These results show a consistent gender difference in
      HSV-1 infection, with a worse outcome in male mice. In addition, the results
      comparing GKO and RGKO mice to controls show differences only in male mice,
      suggesting that some effects of IFN-gamma, a key immunoregulatory molecule, are
      gender specific.

PMID- 11222737
TI  - Floppy SOX: mutual induced fit in hmg (high-mobility group) box-DNA recognition.
AB  - The high-mobility group (HMG) box defines a DNA-bending motif of broad interest
      in relation to human development and disease. Major and minor wings of an L
      shaped structure provide a template for DNA bending. As in the TATA-binding
      protein and a diverse family of factors, insertion of one or more side chains
      between base pairs induces a DNA kink. The HMG box binds in the DNA minor groove
      and may be specific for DNA sequence or distorted DNA architecture. Whereas the
      angular structures of non-sequence-specific domains are well ordered, free SRY
      and related autosomal SOX domains are in part disordered. Observations suggesting
      that the minor wing lacks a fixed tertiary structure motivate the hypothesis that
      DNA bending and stabilization of protein structure define a coupled process. We
      further propose that mutual induced fit in SOX-DNA recognition underlies the
      sequence dependence of DNA bending and enables the induction of promoter-specific
      architectures.

PMID- 11222738
TI  - SRYand architectural gene regulation: the kinetic stability of a bent protein-DNA
      complex can regulate its transcriptional potency.
AB  - Protein-directed DNA bending is proposed to regulate assembly of higher-order DNA
      multiprotein complexes (enhanceosomes and repressosomes). Because transcriptional
      initiation is a nonequilibrium process, gene expression may be modulated by the
      lifetime of such complexes. The human testis-determining factor SRY contains a
      specific DNA-bending motif, the high-mobility group (HMG) box, and is thus
      proposed to function as an architectural factor. Here, we test the hypothesis
      that the kinetic stability of a bent HMG box-DNA complex can in itself modulate
      transcriptional potency. Our studies employ a cotransfection assay in a mammalian
      gonadal cell line as a model for SRY-dependent transcriptional activation.
      Whereas sex-reversal mutations impair SRY-dependent gene expression, an
      activating substitution is identified that enhances SRY's potency by 4-fold. The
      substitution (I13F in the HMG box; fortuitously occurring in chimpanzees) affects
      the motif's cantilever side chain, which inserts between base pairs to disrupt
      base pairing. An aromatic F13 cantilever prolongs the lifetime of the DNA complex
      to an extent similar to its enhanced function. By contrast, equilibrium
      properties (specific DNA affinity, specificity, and bending; thermodynamic
      stability and cellular expression) are essentially unchanged. This correlation
      between potency and lifetime suggests a mechanism of kinetic control. We propose
      that a locked DNA bend enables multiple additional rounds of transcriptional
      initiation per promoter. This model predicts the occurrence of a novel class of
      clinical variants: bent but unlocked HMG box-DNA complexes with native affinity
      and decreased lifetime. Aromatic DNA-intercalating agents exhibit analogous
      kinetic control of transcriptional elongation whereby chemotherapeutic potencies
      correlate with drug-DNA dissociation rates.

PMID- 11222739
TI  - Three-dimensional structure of human follicle-stimulating hormone.
AB  - The crystal structure of a betaThr26Ala mutant of human follicle-stimulating
      hormone (hFSH) has been determined to 3.0 A resolution. The hFSH mutant was
      expressed in baculovirus-infected Hi5 insect cells and purified by affinity
      chromatography, using a betahFSH-specific monoclonal antibody. The betaThr26Ala
      mutation results in elimination of the betaAsn24 glycosylation site, yielding
      protein more suitable for crystallization without affecting the receptor binding
      and signal transduction activity of the glycohormone. The crystal structure has
      two independent hFSH molecules in the asymmetric unit and a solvent content of
      about 80%. The alpha- and betasubunits of hFSH have similar folds, consisting of
      central cystine-knot motifs from which three beta-hairpins extend. The two
      subunits associate very tightly in a head-to-tail arrangement, forming an
      elongated, slightly curved structure, similar to that of human chorionic
      gonadotropin (hCG). The hFSH heterodimers differ only in the conformations of the
      amino and carboxy termini and the second loop of the beta-subunit (L2beta).
      Detailed comparison of the structures of hFSH and hCG reveals several differences
      in the beta-subunits that may be important with respect to receptor binding
      specificity or signal transduction. These differences include conformational
      changes and/or differential distributions of polar or charged residues in loops
      L3beta (hFSH residues 62-73), the cystine noose, or determinant loop (residues 87
      94), and the carboxy-terminal loop (residues 94-104). An additional interesting
      feature of the hFSH structure is an extensive hydrophobic patch in the area
      formed by loops alphaL1, alphaL3, and betaL2. Glycosylation at alphaAsn52 is well
      known to be required for full signal transduction activity and heterodimer
      stability. The structure reveals an intersubunit hydrogen bonding interaction
      between this carbohydrate and betaTyr58, an indication of a mechanism by which
      the carbohydrate may stabilize the heterodimer.

PMID- 11222740
TI  - Insertional mutagenesis of the arginine cage domain of the gonadotropin-releasing
      hormone receptor.
AB  - The pattern of side-chain conservation at the cytoplasmic side of the third
      transmembrane domain of rhodopsin family G protein-coupled receptors, Asp/Glu-Arg
      Tyr/X-X-X-Ile/Val, defines a structural "arginine cage" domain. Previous
      computational and mutagenesis studies of the GnRH receptor indicated an important
      contribution of local interactions to the function of this domain. We have
      investigated the functional importance of the intrahelical position and
      orientation of the arginine cage using insertional mutagenesis. Introduction of a
      single Ala proximal to the conserved Asp-Arg of this domain caused loss of
      detectable ligand binding. Inserting a second Ala, however, restored high
      affinity agonist binding. Further insertion of three or four Ala residues at this
      site generated receptors that bound agonist with an affinity 3- to 10-fold higher
      than that of the wild-type receptor. Loss of detectable coupling to inositol
      phosphate turnover in all these mutant receptors confirms that the structure
      required in this region for efficient signaling is highly constrained. In
      contrast, the recovery of agonist binding with the progressive insertion of two
      to four Ala residues indicates that specific orientations of this segment can
      stabilize high-affinity receptor conformations that are uncoupled from signal
      transduction.

PMID- 11222741
TI  - Hormone selectivity in thyroid hormone receptors.
AB  - Separate genes encode thyroid hormone receptor subtypes TRalpha (NR1A1) and
      TRbeta (NR1A2). Products from each of these contribute to hormone action, but the
      subtypes differ in tissue distribution and physiological response. Compounds that
      discriminate between these subtypes in vivo may be useful in treating important
      medical problems such as obesity and hypercholesterolemia. We previously
      determined the crystal structure of the rat (r) TRalpha ligand-binding domain
      (LBD). In the present study, we determined the crystal structure of the rTRalpha
      LBD in a complex with an additional ligand, Triac (3,5, 3'-triiodothyroacetic
      acid), and two crystal structures of the human (h) TRbeta receptor LBD in a
      complex with either Triac or a TRbeta-selective compound, GC-1 [3,5-dimethyl-4
      (4'-hydroy-3'-isopropylbenzyl)-phenoxy acetic acid]. The rTRalpha and hTRbeta
      LBDs show close structural similarity. However, the hTRbeta structures extend
      into the DNA-binding domain and allow definition of a structural "hinge" region
      of only three amino acids. The two TR subtypes differ in the loop between helices
      1 and 3, which could affect both ligand recognition and the effects of ligand in
      binding coactivators and corepressors. The two subtypes also differ in a single
      amino acid residue in the hormone-binding pocket, Asn (TRbeta) for Ser (TRalpha).
      Studies here with TRs in which the subtype-specific residue is exchanged suggest
      that most of the selectivity in binding derives from this amino acid difference.
      The flexibility of the polar region in the TRbeta receptor, combined with
      differential recognition of the chemical group at the 1-carbon position, seems to
      stabilize the complex with GC-1 and contribute to its beta-selectivity. These
      results suggest a strategy for development of subtype-specific compounds
      involving modifications of the ligand at the 1-position.

PMID- 11222742
TI  - Combined pituitary hormone deficiency due to the F135C human Pit-1 (pituitary
      specific factor 1) gene mutation: functional and structural correlates.
AB  - The pituitary-specific transcription factor Pit-1 (pituitary-specific factor 1)
      is known to play a key role in the differentiation of PRL-, GH-, and TSH
      secreting cells, and in the regulation of expression of the corresponding genes.
      In recent years, 12 distinct mutations of the Pit-1 gene have been shown to be
      responsible for a phenotype of multiple congenital pituitary hormone deficiency
      involving PRL, GH, and TSH. We had previously identified, in four siblings with
      GH, PRL, and TSH deficiencies, a mutation (F135C) resulting in a single amino
      acid change within the POU-specific binding domain of the Pit-1 molecule. In the
      present report, we have explored the functional effect of the F135C mutation. In
      vitro activity tests performed by transfection in human HeLa cells showed
      decreased transactivation capacity on the PRL, GH, and Pit-1 genes. The DNA
      binding experiments performed by gel shift showed that the F135C mutation
      generated a protein capable of binding to DNA response elements. To analyze how
      the F135C mutation might affect functionality of the transcription factor despite
      a normal DNA binding, we used a structure modelization approach and also analyzed
      two other Pit-1 mutant proteins (F135A and F135Y). The loss of functionality in
      these two mutants was similar to that of F135C. This finding was in keeping with
      our molecular modeling studies. According to structural data derived from the
      crystallographic analysis of the DNA/Pit-1 POU domain complex, the conformation
      of the first helix of the F135C-mutated POU-specific domain could be perturbed to
      such an extent that any interaction with other transcription cofactors might be
      definitively prevented.

PMID- 11222743
TI  - Probing conformational changes in the estrogen receptor: evidence for a partially
      unfolded intermediate facilitating ligand binding and release.
AB  - Because the ligand bound to the ligand-binding domain (LBD) of nuclear hormone
      receptors is completely enveloped by protein, it is thought that the process of
      ligand binding or unbinding must involve a significant conformational change of
      this domain. We have used the intrinsic tryptophan fluorescence of the estrogen
      receptor-alpha (ERalpha) or estrogen receptor-beta (ERbeta) LBD, as well as bis
      anilinonaphthalenesulfonate (bis-ANS), a probe for accessible interior regions of
      protein, to follow the guanidine-hydrochloride (Gua-HCl)-induced unfolding of
      this domain. In both cases, we find that the ER-LBD unfolding follows a two-phase
      process. At low Gua-HCl, the ER-LBD undergoes partial unfolding, whereas at high
      Gua-HCl, this domain undergoes a global unfolding, with bis-ANS binding
      preferentially to the partially unfolded state. The partially unfolded state of
      the ERalpha-LBD induced by denaturant does not bind ligand stably, but it may
      resemble an intermediate that this domain accesses transiently under native
      conditions that allow ligands to enter or exit the ligand-binding pocket.

PMID- 11222744
TI  - Regulation of Ca2+-sensitive adenylyl cyclase in gonadotropin-releasing hormone
      neurons.
AB  - In immortalized GnRH neurons, cAMP production is elevated by increased
      extracellular Ca2+ and the Ca2+ channel agonist, BK-8644, and is diminished by
      low extracellular Ca2+ and treatment with nifedipine, consistent with the
      expression of adenylyl cyclase type I (AC I). Potassium-induced depolarization of
      GT1-7 neurons causes a dose-dependent monotonic increase in [Ca2+]i and elicits a
      bell-shaped cAMP response. The inhibitory phase of the cAMP response is prevented
      by pertussis toxin (PTX), consistent with the activation of G(i)-related proteins
      during depolarization. Agonist activation of the endogenous GnRH receptor in GT1
      7 neurons also elicits a bell-shaped change in cAMP production. The inhibitory
      action of high GnRH concentrations is prevented by PTX, indicating coupling of
      the GnRH receptors to G(i)-related proteins. The stimulation of cAMP production
      by activation of endogenous LH receptors is enhanced by low (nanomolar)
      concentrations of GnRH but is abolished by micromolar concentrations of GnRH,
      again in a PTX-sensitive manner. These findings indicate that GnRH neuronal cAMP
      production is maintained by Ca2+ entry through voltage-sensitive calcium
      channels, leading to activation of Ca2+-stimulated AC I. Furthermore, the Ca2+
      influx-dependent activation of AC I acts in conjunction with AC-regulatory G
      proteins to determine basal and agonist-stimulated levels of cAMP production.

PMID- 11222745
TI  - Role of signal transducers and activators of transcription 1 and -3 in inducible
      regulation of the human angiotensinogen gene by interleukin-6.
AB  - The circulating level of angiotensinogen (AGT) is dynamically regulated as an
      important determinant of blood pressure and electrolyte homeostasis. Because the
      mechanisms controlling the regulated expression of human angiotensinogen (hAGT)
      are unknown, we investigated the inducible regulation of the hAGT gene in well
      differentiated HepG2 cells. Interleukin-6 (IL-6) stimulation produced a 3.2-fold
      increase in hAGT mRNA peaking at 96 h after stimulation. Deletional mutagenesis
      of the hAGT promoter in transient transfection assays identified an IL-6 response
      domain between nucleotides -350 and -122 containing three reiterated motifs,
      termed human acute phase response elements (hAPREs). Although mutation of each
      site individually caused a fall in IL-6-inducible luciferase activity, mutation
      of all three sites was required to block the IL-6 effect. Electrophoretic
      mobility shift assay (EMSA), supershift, and microaffinity DNA binding assays
      indicate IL-6-inducible high-affinity binding of signal transducers and
      activators of transcription 1 and -3 (STAT1 and -3) to hAPRE1 and -3 but only low
      affinity binding to hAPRE2. Expression of a dominant-negative form of STAT3, but
      not STAT1, produced a concentration-dependent reduction in IL-6-induced hAGT
      transcription and endogenous mRNA expression. These data indicate that STAT3
      plays a major role in hAGT gene induction through three functionally distinct
      hAPREs in its promoter and suggest a mechanism for its up-regulation during the
      acute-phase response.

PMID- 11222746
TI  - Heterodimerization between the glucocorticoid receptor and the unrelated DNA
      binding protein, Xenopus glucocorticoid receptor accessory factor.
AB  - The adrenal steroid hormones, glucocorticoids, control many physiological
      responses to trauma, including elevated synthesis of fibrinogen, a major blood
      clotting protein. Glucocorticoid regulation of the gamma-fibrinogen subunit gene
      in Xenopus laevis is mediated by a binding site for Xenopus glucocorticoid
      receptor accessory factor (XGRAF) and a contiguous glucocorticoid response
      element (GRE) half-site. Here, we characterize the protein:DNA complex formed by
      a cooperative interaction between XGRAF, GR, and the DNA. We demonstrate that the
      complex contains XGRAF by competition in a gel shift assay. The presence of GR is
      established by two criteria: 1) size dependence of the XGRAF:GR:DNA complex on
      the size of the GR component and 2) interference with complex formation by GR
      antibody. Cooperative binding of XGRAF and GR to the DNA was quantitated, showing
      that GR favors binding to XGRAF:DNA compared with free DNA by a factor of 30. The
      cooperative interaction between XGRAF and GR can occur on nicked DNA but is
      disrupted when 1 bp is inserted between the XGRAF binding site and half-GRE.
      Significantly, this loss of physical association in vitro correlates with loss of
      XGRAF amplification of GR activity in transiently transfected primary Xenopus
      hepatocytes. The simplest explanation for cooperativity between XGRAF and GR is
      formation of a DNA-bound heterodimer of these two proteins. This mechanism
      represents a new mode of transcriptional regulation in which GR and a nonreceptor
      protein form a heterodimer, with both partners contacting their specific DNA
      sites simultaneously.

PMID- 11222747
TI  - Distinct tissue-specific roles for thyroid hormone receptors beta and alpha1 in
      regulation of type 1 deiodinase expression.
AB  - Type 1 deiodinase (D1) metabolizes different forms of thyroid hormones to control
      levels of T3, the active ligand for thyroid hormone receptors (TR). The D1 gene
      is itself T3-inducible and here, the regulation of D1 expression by TRalpha1 and
      TRbeta, which act as T3-dependent transcription factors, was investigated in
      receptor-deficient mice. Liver and kidney D1 mRNA and activity levels were
      reduced in TRbeta(-/-) but not TRalpha1(-/-) mice. Liver D1 remained weakly T3
      inducible in TRbeta(-/-) mice whereas induction was abolished in double mutant
      TRalpha1(-/-)TRbeta(-/-) mice. This indicates that TRbeta is primarily
      responsible for regulating D1 expression whereas TRalpha1 has only a minor role.
      In kidney, despite the expression of both TRalpha1 and TRbeta, regulation relied
      solely on TRbeta, thus revealing a marked tissue restriction in TR isotype
      utilization. Although TRbeta and TRalpha1 mediate similar functions in vitro,
      these results demonstrate differential roles in regulating D1 expression in vivo
      and suggest that tissue-specific factors and structural distinctions between TR
      isotypes contribute to functional specificity. Remarkably, there was an
      obligatory requirement for a TR, whether TRbeta or TRalpha1, for any detectable
      D1 expression in liver. This suggests a novel paradigm of gene regulation in
      which the TR sets both basal expression and the spectrum of induced states.
      Physiologically, these findings suggest a critical role for TRbeta in regulating
      the thyroid hormone status through D1-mediated metabolism.

PMID- 11222748
TI  - Beta-cell differentiation from a human pancreatic cell line in vitro and in vivo.
AB  - Cell transplantation therapy for diabetes is limited by an inadequate supply of
      cells exhibiting glucose-responsive insulin secretion. To generate an unlimited
      supply of human beta-cells, inducibly transformed pancreatic beta-cell lines have
      been created by expression of dominant oncogenes. The cell lines grow
      indefinitely but lose differentiated function. Induction of beta-cell
      differentiation was achieved by stimulating the signaling pathways downstream of
      the transcription factor PDX-1, cell-cell contact, and the glucagon-like peptide
      (GLP-1) receptor. Synergistic activation of those pathways resulted in
      differentiation into functional beta-cells exhibiting glucose-responsive insulin
      secretion in vitro. Both oncogene-expressing and oncogene-deleted cells were
      transplanted into nude mice and found to exhibit glucose-responsive insulin
      secretion in vivo. The ability to grow unlimited quantities of human beta-cells
      is a major step toward developing a cell transplantation therapy for diabetes.

PMID- 11222749
TI  - Exoribonuclease superfamilies: structural analysis and phylogenetic distribution.
AB  - Exoribonucleases play an important role in all aspects of RNA metabolism.
      Biochemical and genetic analyses in recent years have identified many new RNases
      and it is now clear that a single cell can contain multiple enzymes of this
      class. Here, we analyze the structure and phylogenetic distribution of the known
      exoribonucleases. Based on extensive sequence analysis and on their catalytic
      properties, all of the exoribonucleases and their homologs have been grouped into
      six superfamilies and various subfamilies. We identify common motifs that can be
      used to characterize newly-discovered exoribonucleases, and based on these motifs
      we correct some previously misassigned proteins. This analysis may serve as a
      useful first step for developing a nomenclature for this group of enzymes.

PMID- 11222750
TI  - Fluorescent RNA cytochemistry: tracking gene transcripts in living cells.
AB  - The advent of jellyfish green fluorescent protein and its spectral variants,
      together with promising new fluorescent proteins from other classes of the
      Cnidarian phylum (coral and anemones), has greatly enhanced and promises to
      further boost the detection and localization of proteins in cell biology. It has
      been less widely appreciated that highly sensitive methods have also recently
      been developed for detecting the movement and localization in living cells of the
      very molecules that precede proteins in the gene expression pathway, i.e. RNAs.
      These approaches include the microinjection of fluorescent RNAs into living
      cells, the in vivo hybridization of fluorescent oligonucleotides to endogenous
      RNAs and the expression in cells of fluorescent RNA-binding proteins. This new
      field of 'fluorescent RNA cytochemistry' is summarized in this article, with
      emphasis on the biological insights it has already provided. These new techniques
      are likely to soon collaborate with other emerging approaches to advance the
      investigation of RNA birth, RNA-protein assembly and ribonucleoprotein particle
      transport in systems such as oocytes, embryos, neurons and other somatic cells,
      and may even permit the observation of viral replication and transcription
      pathways as they proceed in living cells, ushering in a new era of nucleic acids
      research in vivo.

PMID- 11222751
TI  - Sp1 phosphorylation regulates inducible expression of platelet-derived growth
      factor B-chain gene via atypical protein kinase C-zeta.
AB  - Platelet-derived growth factor (PDGF) is a broadly expressed mitogenic and
      chemotactic factor with diverse roles in a number of physiologic and pathologic
      settings. The zinc finger transcription factors Sp1, Sp3 and Egr-1 bind to
      overlapping elements in the proximal PDGF B-chain promoter and activate
      transcription of this gene. The anthracycline nogalamycin has previously been
      reported to inhibit the capacity of Egr-1 to bind DNA in vitro. Here we used
      electrophoretic mobility shift assays to show that nogalamycin added to cells in
      culture did not alter the interaction of Egr-1 with the PDGF-B promoter. Instead,
      it enhanced the capacity of Sp1 to bind DNA. Nogalamycin increased PDGF-B mRNA
      expression at the level of transcription, which was abrogated by mutation of the
      Sp1 binding site in the PDGF-B promoter or overexpression of mutant Sp1. Rather
      than increasing total levels of Sp1, nogalamycin altered the phosphorylation
      state of the transcription factor. Overexpression of dominant-negative PKC-zeta
      blocked nogalamycin-inducible Sp1 phosphorylation and PDGF-B promoter-dependent
      expression. Nogalamycin stimulated the phosphorylation of PKC-zeta (on residue
      Thr(410)). These findings demonstrate for the first time that PKC-zeta and Sp1
      phosphorylation mediate the inducible expression of this growth factor.

PMID- 11222752
TI  - Statistical prediction of single-stranded regions in RNA secondary structure and
      application to predicting effective antisense target sites and beyond.
AB  - Single-stranded regions in RNA secondary structure are important for RNA-RNA and
      RNA-protein interactions. We present a probability profile approach for the
      prediction of these regions based on a statistical algorithm for sampling RNA
      secondary structures. For the prediction of phylogenetically-determined single
      stranded regions in secondary structures of representative RNA sequences, the
      probability profile offers substantial improvement over the minimum free energy
      structure. In designing antisense oligonucleotides, a practical problem is how to
      select a secondary structure for the target mRNA from the optimal structure(s)
      and many suboptimal structures with similar free energies. By summarizing the
      information from a statistical sample of probable secondary structures in a
      single plot, the probability profile not only presents a solution to this
      dilemma, but also reveals 'well-determined' single-stranded regions through the
      assignment of probabilities as measures of confidence in predictions. In
      antisense application to the rabbit beta-globin mRNA, a significant correlation
      between hybridization potential predicted by the probability profile and the
      degree of inhibition of in vitro translation suggests that the probability
      profile approach is valuable for the identification of effective antisense target
      sites. Coupling computational design with DNA-RNA array technique provides a
      rational, efficient framework for antisense oligonucleotide screening. This
      framework has the potential for high-throughput applications to functional
      genomics and drug target validation.

PMID- 11222753
TI  - Transcriptional activation by hepatocyte nuclear factor-4 in a cell-free system
      derived from rat liver nuclei.
AB  - Hepatocyte nuclear factor-4 (HNF4) regulates gene expression by binding to direct
      repeat motifs of the RG(G/T)TCA sequence separated by one nucleotide (DR1). In
      this study we demonstrate that endogenous HNF4 present in rat liver nuclear
      extracts, as well as purified recombinant HNF4, activates transcription from
      naked DNA templates containing multiple copies of the DR1 element linked to the
      adenovirus major late promoter. Recombinant HNF4 also activates transcription
      from the rat cellular retinol binding protein II (CRBPII) promoter in vitro. The
      region between -105 and -63 bp of this promoter is essential for HNF-mediated
      transactivation. The addition of a peptide containing the LXXLL motif abolished
      HNF4-mediated transactivation in vitro suggesting that LXXLL-containing protein
      factor(s) are involved in HNF4-mediated transactivation in rat liver nuclear
      extracts. This is the first report on transactivation by HNF4 in a cell-free
      system derived from rat liver nuclei.

PMID- 11222754
TI  - Determination of the binding constants of the centromere protein Cbf1 to all 16
      centromere DNAs of Saccharomyces cerevisiae.
AB  - Cbf1p is a Saccharomyces cerevisiae chromatin protein belonging to the basic
      region helix-loop-helix leucine zipper (bHLHzip) family of DNA binding proteins.
      Cbf1p binds to a conserved element in the 5'-flanking region of methionine
      biosynthetic genes and to centromere DNA element I (CDEI) of S.cerevisiae
      centromeric DNA. We have determined the apparent equilibrium dissociation
      constants of Cbf1p binding to all 16 CDEI DNAs in gel retardation assays. Binding
      constants of full-length Cbf1p vary between 1.7 and 3.8 nM. However, the
      dissociation constants of a Cbf1p deletion variant that has been shown to be
      fully sufficient for Cbf1p function in vivo vary in a range between 3.2 and 12
      nM. In addition, native polyacrylamide gel electrophoresis revealed distinct
      changes in the 3D structure of the Cbf1p/CEN complexes. We also show that the
      previously reported DNA binding stimulation activity of the centromere protein
      p64 functions on both the Cbf1 full-length protein and a deletion variant
      containing only the bHLHzip domain of Cbf1p. Our results suggest that centromeric
      DNA outside the consensus CDEI sequence and interaction of Cbf1p with adjacent
      centromere proteins contribute to the complex formation between Cbf1p and CEN
      DNA.

PMID- 11222756
TI  - The Dictyostelium discoideum family of Rho-related proteins.
AB  - Taking advantage of the ongoing Dictyostelium genome sequencing project, we have
      assembled >73 kb of genomic DNA in 15 contigs harbouring 15 genes and one
      pseudogene of Rho-related proteins. Comparison with EST sequences revealed that
      every gene is interrupted by at least one and up to four introns. For racC
      extensive alternative splicing was identified. Northern blot analysis showed that
      mRNAs for racA, racE, racG, racH and racI were present at all stages of
      development, whereas racJ and racL were expressed only at late stages. Amino acid
      sequences have been analysed in the context of Rho-related proteins of other
      organisms. Rac1a/1b/1c, RacF1/F2 and to a lesser extent RacB and the GTPase
      domain of RacA can be grouped in the Rac subfamily. None of the additional
      Dictyostelium Rho-related proteins belongs to any of the well-defined
      subfamilies, like Rac, Cdc42 or Rho. RacD and RacA are unique in that they lack
      the prenylation motif characteristic of Rho proteins. RacD possesses a 50 residue
      C-terminal extension and RacA a 400 residue C-terminal extension that contains a
      proline-rich region, two BTB domains and a novel C-terminal domain. We have also
      identified homologues for RacA in Drosophila and mammals, thus defining a new
      subfamily of Rho proteins, RhoBTB.

PMID- 11222755
TI  - Identification of human DNA helicase V with the far upstream element-binding
      protein.
AB  - The properties of human DNA helicase V (HDH V) were studied in greater detail
      following an improved purification procedure. From 450 g of cultured cells, <0.1
      mg of pure protein was isolated. HDH V unwinds DNA unidirectionally by moving in
      the 3' to 5' direction along the bound strand in an ATP- and Mg(2+)-dependent
      fashion. The enzyme is not processive and can also unwind partial RNA-RNA
      duplexes such as HDH IV and HDH VIII. The M:(r) determined by SDS-PAGE (66 kDa)
      corresponds to that measured under native conditions, suggesting that HDH V
      exists as a monomer in the nucleus. Microsequencing of the purified HDH V shows
      that this enzyme is identical to the far upstream element-binding protein (FBP),
      a protein that stimulates the activity of the c-myc gene by binding specifically
      to the 'FUSE' DNA region localized upstream of its promoter. The sequence of HDH
      V/FBP contains RGG motifs like HDH IV/nucleolin, HDH VIII/G3BP as well as other
      human RNA and DNA helicases identified by other laboratories.

PMID- 11222757
TI  - Functionality of the STNV translational enhancer domain correlates with affinity
      for two wheat germ factors.
AB  - The satellite tobacco necrosis virus RNA is uncapped and requires a 3'
      translational enhancer domain (TED) for translation. Both in the wheat germ
      extract and in tobacco, TED stimulates in cis translation of heterologous,
      uncapped RNAs. In this study we investigated to what extent translation
      stimulation by TED depends on binding to wheat germ factors. We show that in
      vitro TED binds at least seven wheat germ proteins. Translation and crosslinking
      assays, to which TED or TED derivatives with reduced functionality were included
      as competitor, showed that TED function correlates with binding to a 28 kDa
      protein (p28). One particular condition of competition revealed that p28 binding
      is not obligatory for TED function. Under this condition, a 30 kDa protein (p30)
      binds to TED. Importantly, affinity of p30 correlates with functionality of TED.
      These results strongly suggest that TED has the capacity to stimulate translation
      by recruiting the translational machinery either via binding to p28 or via
      binding to p30.

PMID- 11222758
TI  - Ethidium derivatives bind to G-quartets, inhibit telomerase and act as
      fluorescent probes for quadruplexes.
AB  - The telomeric G-rich single-stranded DNA can adopt in vitro an intramolecular
      quadruplex structure, which has been shown to directly inhibit telomerase
      activity. The reactivation of this enzyme in immortalized and most cancer cells
      suggests that telomerase is a relevant target in oncology, and telomerase
      inhibitors have been proposed as new potential anticancer agents. In this paper,
      we describe ethidium derivatives that stabilize G-quadruplexes. These molecules
      were shown to increase the melting temperature of an intramolecular quadruplex
      structure, as shown by fluorescence and absorbance measurements, and to
      facilitate the formation of intermolecular quadruplex structures. In addition,
      these molecules may be used to reveal the formation of multi-stranded DNA
      structures by standard fluorescence imaging, and therefore become fluorescent
      probes of quadruplex structures. This recognition was associated with telomerase
      inhibition in vitro: these derivatives showed a potent anti-telomerase activity,
      with IC(50) values of 18-100 nM in a standard TRAP assay.

PMID- 11222759
TI  - Radical SAM, a novel protein superfamily linking unresolved steps in familiar
      biosynthetic pathways with radical mechanisms: functional characterization using
      new analysis and information visualization methods.
AB  - A novel protein superfamily with over 600 members was discovered by iterative
      profile searches and analyzed with powerful bioinformatics and information
      visualization methods. Evidence exists that these proteins generate a radical
      species by reductive cleavage of S:-adenosylmethionine (SAM) through an unusual
      Fe-S center. The superfamily (named here Radical SAM) provides evidence that
      radical-based catalysis is important in a number of previously well- studied but
      unresolved biochemical pathways and reflects an ancient conserved mechanistic
      approach to difficult chemistries. Radical SAM proteins catalyze diverse
      reactions, including unusual methylations, isomerization, sulfur insertion, ring
      formation, anaerobic oxidation and protein radical formation. They function in
      DNA precursor, vitamin, cofactor, antibiotic and herbicide biosynthesis and in
      biodegradation pathways. One eukaryotic member is interferon-inducible and is
      considered a candidate drug target for osteoporosis; another is observed to bind
      the neuronal Cdk5 activator protein. Five defining members not previously
      recognized as homologs are lysine 2,3-aminomutase, biotin synthase, lipoic acid
      synthase and the activating enzymes for pyruvate formate-lyase and anaerobic
      ribonucleotide reductase. Two functional predictions for unknown proteins are
      made based on integrating other data types such as motif, domain, operon and
      biochemical pathway into an organized view of similarity relationships.

PMID- 11222760
TI  - Excision of 8-oxoguanine within clustered damage by the yeast OGG1 protein.
AB  - Clustered damages are formed in DNA by ionising radiation and radiomimetic
      anticancer agents and are thought to be biologically severe. 7,8-dihydro-8
      oxoguanine (8-oxoG), a major DNA damage resulting from oxidative attack, is
      highly mutagenic leading to a high level of G.C-->T.A transversions if not
      previously excised by OGG1 DNA glycosylase/AP lyase proteins in eukaryotes.
      However, 8-oxoG within clustered DNA damage may present a challenge to the repair
      machinery of the cell. The ability of yeast OGG1 to excise 8-oxoG was determined
      when another type of damage [dihydrothymine, uracil, 8-oxoG, abasic (AP) site or
      various types of single-strand breaks (SSBs)] is present on the complementary
      strand 1, 3 or 5 bases 5' or 3' opposite to 8-oxoG. Base damages have little or
      no influence on the excision of 8-oxoG by yeast OGG1 (yOGG1) whereas an AP site
      has a strong inhibitory effect. Various types of SSBs, obtained using either
      oligonucleotides with 3'- and 5'-phosphate termini around a gap or through
      conversion of an AP site with either endonuclease III or human AP endonuclease 1,
      strongly inhibit excision of 8-oxoG by yOGG1. Therefore, this large inhibitory
      effect of an AP site or a SSB may minimise the probability of formation of a
      double-strand break in the processing of 8-oxoG within clustered damages.

PMID- 11222761
TI  - PCR candidate region mismatch scanning: adaptation to quantitative, high
      throughput genotyping.
AB  - Linkage and association analyses were performed to identify loci affecting
      disease susceptibility by scoring previously characterized sequence variations
      such as microsatellites and single nucleotide polymorphisms. Lack of markers in
      regions of interest, as well as difficulty in adapting various methods to high
      throughput settings, often limits the effectiveness of the analyses. We have
      adapted the Escherichia coli mismatch detection system, employing the factors
      MutS, MutL and MutH, for use in PCR-based, automated, high-throughput genotyping
      and mutation detection of genomic DNA. Optimal sensitivity and signal-to-noise
      ratios were obtained in a straightforward fashion because the detection reaction
      proved to be principally dependent upon monovalent cation concentration and MutL
      concentration. Quantitative relationships of the optimal values of these
      parameters with length of the DNA test fragment were demonstrated, in support of
      the translocation model for the mechanism of action of these enzymes, rather than
      the molecular switch model. Thus, rapid, sequence-independent optimization was
      possible for each new genomic target region. Other factors potentially limiting
      the flexibility of mismatch scanning, such as positioning of dam recognition
      sites within the target fragment, have also been investigated. We developed
      several strategies, which can be easily adapted to automation, for limiting the
      analysis to intersample heteroduplexes. Thus, the principal barriers to the use
      of this methodology, which we have designated PCR candidate region mismatch
      scanning, in cost-effective, high-throughput settings have been removed.

PMID- 11222762
TI  - Comparative mutational analysis of cis-acting RNA signals for translational
      frameshifting in HIV-1 and HTLV-2.
AB  - Human immunodeficiency virus type 1 (HIV-1) and human T cell leukemia virus type
      II (HTLV-2) use a similar mechanism for -1 translational frameshifting to
      overcome the termination codon in viral RNA at the end of the gag gene. Previous
      studies have identified two important RNA signals for frameshifting, the slippery
      sequence and a downstream stem-loop structure. However, there have been somewhat
      conflicting reports concerning the individual contributions of these sequences.
      In this study we have performed a comprehensive mutational analysis of the cis
      acting RNA sequences involved in HIV-1 gag-pol and HTLV-2 gag-pro frameshifting.
      Using an in vitro translation system we determined frameshifting efficiencies for
      shuffled HIV-1/HTLV-2 RNA elements in a background of HIV-1 or HTLV-2 sequences.
      We show that the ability of the slippery sequence and stem-loop to promote
      ribosomal frameshifting is influenced by the flanking upstream sequence and the
      nucleotides in the spacer element. A wide range of frameshift efficiency rates
      was observed for both viruses when shuffling single sequence elements. The
      results for HIV-1/HTLV-2 chimeric constructs represent strong evidence supporting
      the notion that the viral wild-type sequences are not designed for maximal
      frameshifting activity but are optimized to a level suited to efficient viral
      replication.

PMID- 11222763
TI  - A nicked duplex decamer DNA with a PEG(6) tether.
AB  - A dumbbell double-stranded DNA decamer tethered with a hexaethylene glycol linker
      moiety (DDSDPEG), with a nick in the centre of one strand, has been synthesised.
      The standard NMR methods, E.COSY, TOCSY, NOESY and HMQC, were used to measure
      (1)H, (31)P and T:(1) spectral parameters. Molecular modelling using rMD
      simulated annealing was used to compute the structure. Scalar couplings and
      dipolar contacts show that the molecule adopts a right-handed B-DNA helix in 38
      mM phosphate buffer at pH 7. Its high melting temperature confirms the good base
      stacking and stability of the duplex. This is partly attributed to the presence
      of the PEG(6) linker at both ends of the duplex that restricts the dynamics of
      the stem pentamers and thus stabilises the oligonucleotide. The inspection of the
      global parameters shows that the linker does not distort the B-DNA geometry. The
      computed structure suggests that the presence of the nick is not disturbing the
      overall tertiary structure, base pair geometry or duplex base pairing to a
      substantial extent. The nick has, however, a noticeable impact on the local
      geometry at the nick site, indicated clearly by NMR analysis and reflected in the
      conformational parameters of the computed structure. The (1)H spectra also show
      much sharper resonances in the presence of K(+) indicating that conformational
      heterogeneity of DDSDPEG is reduced in the presence of potassium as compared to
      sodium or caesium ions. At the same time the (1)H resonances have longer T:(1)
      times. This parameter is suggested as a sensitive gauge of stabilisation.

PMID- 11222765
TI  - Polysomal ribonuclease 1 exists in a latent form on polysomes prior to estrogen
      activation of mRNA decay.
AB  - Estrogen induces a global change in the translation profile of Xenopus
      hepatocytes, replacing serum protein synthesis with production of the yolk
      protein precursor vitellogenin. This is accomplished by the coordinate
      destabilization of serum protein mRNAs and the transcriptional induction and
      subsequent stabilization of vitellogenin mRNA. Previous work identified an
      endonuclease activity whose appearance on polysomes correlated with the
      disappearance of serum protein mRNAs. This enzyme, polysomal ribonuclease 1
      (PMR1), is a novel member of the peroxidase gene family. The current study
      examined the association of PMR1 with its mRNA targets on polysomes and mRNPs.
      The highest amount of polysome-bound PMR1 was observed prior to estrogen
      induction of mRNA decay. Its distribution on sucrose density gradients matched
      the absorbance profile of polysome-bound mRNA, suggesting that PMR1 forms a
      latent complex with mRNA. Following dissociation with EDTA the 62 kDa PMR1
      sedimented with a larger complex of >670 kDa. Estrogen induces a 22-fold increase
      in unit enzymatic activity of polysome-bound PMR1, and a time-dependent loss of
      PMR1 from polysomes in a manner that mirrors the disappearance of albumin mRNA.
      These data suggest that the key step in the extensive estrogen-induced change in
      mRNA decay in Xenopus liver is activation of a latent mRNA endonuclease
      associated with its target mRNA.

PMID- 11222764
TI  - Characterization and mutational analysis of yeast Dbp8p, a putative RNA helicase
      involved in ribosome biogenesis.
AB  - RNA helicases of the DEAD box family are involved in almost all cellular
      processes involving RNA molecules. Here we describe functional characterization
      of the yeast RNA helicase Dbp8p (YHR169w). Our results show that Dbp8p is an
      essential nucleolar protein required for biogenesis of the small ribosomal
      subunit. In vivo depletion of Dbp8p resulted in a ribosomal subunit imbalance due
      to a deficit in 40S ribosomal subunits. Subsequent analyses of pre-rRNA
      processing by pulse-chase labeling, northern hybridization and primer extension
      revealed that the early steps of cleavage of the 35S precursor at sites A(1) and
      A(2) are inhibited and delayed at site A(0). Synthesis of 18S rRNA, the RNA
      moiety of the 40S subunit, is thereby blocked in the absence of Dbp8p. The
      involvement of Dbp8p as a bona fide RNA helicase in ribosome biogenesis is
      strongly supported by the loss of Dbp8p in vivo function obtained by site
      directed mutagenesis of some conserved motifs carrying the enzymatic properties
      of the protein family.

PMID- 11222766
TI  - In vitro roles of invariant helix-turn-helix motif residue R383 in sigma(54)
      (sigma(N)).
AB  - In vitro DNA-binding and transcription properties of sigma(54) proteins with the
      invariant Arg383 in the putative helix-turn-helix motif of the DNA-binding domain
      substituted by lysine or alanine are described. We show that R383 contributes to
      maintaining stable holoenzyme-promoter complexes in which limited DNA opening
      downstream of the -12 GC element has occurred. Unlike wild-type sigma(54),
      holoenzymes assembled with the R383A or R383K mutants could not form activator
      independent, heparin-stable complexes on heteroduplex Sinorhizobium meliloti nifH
      DNA mismatched next to the GC. Using longer sequences of heteroduplex DNA,
      heparin-stable complexes formed with the R383K and, to a lesser extent, R383A
      mutant holoenzymes, but only when the activator and a hydrolysable nucleotide was
      added and the DNA was opened to include the -1 site. Although R383 appears
      inessential for polymerase isomerisation, it makes a significant contribution to
      maintaining the holoenzyme in a stable complex when melting is initiating next to
      the GC element. Strikingly, Cys383-tethered FeBABE footprinting of promoter DNA
      strongly suggests that R383 is not proximal to promoter DNA in the closed
      complex. This indicates that R383 is not part of the regulatory centre in the
      sigma(54) holoenzyme, which includes the -12 promoter region elements. R383
      contributes to several properties, including core RNA polymerase binding and to
      the in vivo stability of sigma(54).

PMID- 11222767
TI  - RegA proteins from phage T4 and RB69 have conserved helix-loop groove RNA binding
      motifs but different RNA binding specificities.
AB  - The RegA proteins from the bacteriophage T4 and RB69 are translational repressors
      that control the expression of multiple phage mRNAs. RegA proteins from the two
      phages share 78% sequence identity; however, in vivo expression studies have
      suggested that the RB69 RegA protein binds target RNAs with a higher affinity
      than T4 RegA protein. To study the RNA binding properties of T4 and RB69 RegA
      proteins more directly, the binding sites of RB69 RegA protein on synthetic RNAs
      corresponding to the translation initiation region of two RB69 target genes were
      mapped by RNase protection assays. These assays revealed that RB69 RegA protein
      protects nucleotides -9 to -3 (relative to the start codon) on RB69 gene 44,
      which contains the sequence GAAAAUU. On RB69 gene 45, the protected site
      (nucleotides -8 to -3) contains a similar purine-rich sequence: GAAAUA.
      Interestingly, T4 RegA protein protected the same nucleotides on these RNAs. To
      examine the specificity of RNA binding, quantitative RNA gel shift assays were
      performed with synthetic RNAs corresponding to recognition elements (REs) in
      three T4 and three RB69 mRNAs. Comparative gel shift assays demonstrated that
      RB69 RegA protein has an approximately 7-fold higher affinity for T4 gene 44 RE
      RNA than T4 RegA protein. RB69 RegA protein also binds RB69 gene 44 RE RNA with a
      4-fold higher affinity than T4 RegA protein. On the other hand, T4 RegA exhibited
      a higher affinity than RB69 RegA protein for RB69 gene 45 RE RNA. With respect to
      their affinities for cognate RNAs, both RegA proteins exhibited the following
      hierarchy of affinities: gene 44 > gene 45 > regA. Interestingly, T4 RegA
      exhibited the highest affinity towards RB69 gene 45 RE RNA, whereas RB69 RegA
      protein had the highest affinity for T4 gene 44 RE RNA. The helix-loop groove RNA
      binding motif of T4 RegA protein is fully conserved in RB69 RegA protein.
      However, homology modeling of the structure of RB69 RegA protein reveals that the
      divergent residues are clustered in two areas of the surface, and that there are
      two large areas of high conservation near the helix-loop groove, which may also
      play a role in RNA binding.

PMID- 11222768
TI  - GeneSplicer: a new computational method for splice site prediction.
AB  - GeneSplicer is a new, flexible system for detecting splice sites in the genomic
      DNA of various eukaryotes. The system has been tested successfully using DNA from
      two reference organisms: the model plant Arabidopsis thaliana and human. It was
      compared to six programs representing the leading splice site detectors for each
      of these species: NetPlantGene, NetGene2, HSPL, NNSplice, GENIO and SpliceView.
      In each case GeneSplicer performed comparably to the best alternative, in terms
      of both accuracy and computational efficiency.

PMID- 11222769
TI  - Kinetics of formation of hypoxanthine containing base pairs by HIV-RT: RNA
      template effects on the base substitution frequencies.
AB  - Hypoxanthine (H), the deamination product of adenine, has been implicated in the
      high frequency of A to G transitions observed in retroviral and other RNA
      genomes. Although H.C base pairs are thermodynamically more stable than other H.N
      pairs, polymerase selection may be determined in part by kinetic factors.
      Therefore, the hypoxanthine induced substitution pattern resulting from
      replication by viral polymerases may be more complex than that predicted from
      thermodynamics. We have examined the steady-state kinetics of formation of base
      pairs opposite template H in RNA by HIV-RT, and for the incorporation of dITP
      during first- and second-strand synthesis. Hypoxanthine in an RNA template
      enhances the k(2app) for pairing with standard dNTPs by factors of 10-1000
      relative to adenine at the same sequence position. The order of base pairing
      preferences for H in RNA was observed to be H.C >> H.T > H.A > H.G. Steady-state
      kinetics of insertion for all possible mispairs formed with dITP were examined on
      RNA and DNA templates of identical sequence. Insertion of dITP opposite all bases
      occurs 2-20 times more frequently on RNA templates. This bias for higher
      insertion frequencies on RNA relative to DNA templates is also observed for
      formation of mispairs at template A. This kinetic advantage afforded by RNA
      templates for mismatches and pairing involving H suggests a higher induction of
      mutations at adenines during first-strand synthesis by HIV-RT.

PMID- 11222770
TI  - Y box-binding protein-1 binds preferentially to single-stranded nucleic acids and
      exhibits 3'-->5' exonuclease activity.
AB  - We have previously shown that Y box-binding protein-1 (YB-1) binds preferentially
      to cisplatin-modified Y box sequences. Based on structural and biochemical data,
      we predicted that this protein binds single-stranded nucleic acids. In the
      present study we confirmed the prediction and also discovered some unexpected
      functional features of YB-1. We found that the cold shock domain of the protein
      is necessary but not sufficient for double-stranded DNA binding while the C-tail
      domain interacts with both single-stranded DNA and RNA independently of the cold
      shock domain. In an in vitro translation system the C-tail domain of the protein
      inhibited translation but the cold shock domain did not. Both in vitro pull-down
      and in vivo co-immunoprecipitation assays revealed that YB-1 can form a
      homodimer. Deletion analysis mapped the C-tail domain of the protein as the
      region of homodimerization. We also characterized an intrinsic 3'-->5' DNA
      exonuclease activity of the protein. The region between residues 51 and 205 of
      its 324-amino acid extent is required for full exonuclease activity. Our findings
      suggest that YB-1 functions in regulating DNA/RNA transactions and that these
      actions involve different domains.

PMID- 11222771
TI  - Detection of alkali metal ions in DNA crystals using state-of-the-art X-ray
      diffraction experiments.
AB  - The observation of light metal ions in nucleic acids crystals is generally a
      fortuitous event. Sodium ions in particular are notoriously difficult to detect
      because their X-ray scattering contributions are virtually identical to those of
      water and Na(+.)O distances are only slightly shorter than strong hydrogen bonds
      between well-ordered water molecules. We demonstrate here that replacement of
      Na(+) by K(+), Rb(+) or Cs(+) and precise measurements of anomalous differences
      in intensities provide a particularly sensitive method for detecting alkali metal
      ion-binding sites in nucleic acid crystals. Not only can alkali metal ions be
      readily located in such structures, but the presence of Rb(+) or Cs(+) also
      allows structure determination by the single wavelength anomalous diffraction
      technique. Besides allowing identification of high occupancy binding sites, the
      combination of high resolution and anomalous diffraction data established here
      can also pinpoint binding sites that feature only partial occupancy. Conversely,
      high resolution of the data alone does not necessarily allow differentiation
      between water and partially ordered metal ions, as demonstrated with the crystal
      structure of a DNA duplex determined to a resolution of 0.6 A.

PMID- 11222772
TI  - Prediction of operons in microbial genomes.
AB  - Operon structure is an important organization feature of bacterial genomes. Many
      sets of genes occur in the same order on multiple genomes; these conserved gene
      groupings represent candidate operons. This study describes a computational
      method to estimate the likelihood that such conserved gene sets form operons. The
      method was used to analyze 34 bacterial and archaeal genomes, and yielded more
      than 7600 pairs of genes that are highly likely (P: >/= 0.98) to belong to the
      same operon. The sensitivity of our method is 30-50% for the Escherichia coli
      genome. The predicted gene pairs are available from our World Wide Web site
      http://www.tigr.org/tigr-scripts/operons/operons.cgi.

PMID- 11222773
TI  - Translational control of human p53 expression in yeast mediated by 5'-UTR-ORF
      structural interaction.
AB  - We have expressed human p53 cDNA in the yeast Saccharomyces cerevisiae and shown
      that the level of production and the length of the p53 protein depends on the
      presence of untranslated mRNA regions (UTRs). The expression of the ORF alone
      leads to a p53 protein of correct size (53 kDa) that accumulates to high levels,
      concomitantly with the presence of a small amount of a p40 protein (40 kDa).
      However, when either the entire 5'-UTR and a part of the 3'- or 5'-UTR alone is
      used, this leads to the production of small amounts of the 40 kDa truncated form
      only. The p40 protein corresponds to a truncated form of p53 at the C-terminal
      extremity since it reacts only with a monoclonal antibody recognising the N
      terminal epitope. This effect on the amount and length of p53 protein had no
      correlation at the mRNA level, suggesting that translational control probably
      occurs through the 5'-UTR. We propose a model of structural interaction between
      this UTR and a part of the ORF mRNA for the regulation of p53 expression in this
      heterologous context.

PMID- 11222775
TI  - Phylogenetic relationships among group II intron ORFs.
AB  - Group II introns are widely believed to have been ancestors of spliceosomal
      introns, yet little is known about their own evolutionary history. In order to
      address the evolution of mobile group II introns, we have compiled 71 open
      reading frames (ORFs) related to group II intron reverse transcriptases and
      subjected their derived amino acid sequences to phylogenetic analysis. The
      phylogenetic tree was rooted with reverse transcriptases (RTs) of non-long
      terminal repeat retroelements, and the inferred phylogeny reveals two major
      clusters which we term the mitochondrial and chloroplast-like lineages. Bacterial
      ORFs are mainly positioned at the bases of the two lineages but with weak
      bootstrap support. The data give an overview of an apparently high degree of
      horizontal transfer of group II intron ORFs, mostly among related organisms but
      also between organelles and bacteria. The Zn domain (nuclease) and YADD motif (RT
      active site) were lost multiple times during evolution. Differences in domain
      structures suggest that the oldest ORFs were concise, while the ORF in the
      mitochondrial lineage subsequently expanded in three locations. The data are
      consistent with a bacterial origin for mobile group II introns.

PMID- 11222774
TI  - Regulation of c-maf gene expression by Pax6 in cultured cells.
AB  - c-Maf is a bZip transcription factor expressed in developmental and cellular
      differentiation processes. Recently, a c-maf knockout mouse model, showing
      abnormal lens development, has been reported. In order to study the regulation
      mechanisms of c-maf gene expression during the differentiation process we have
      cloned and functionally characterized the rat c-maf (maf-2) gene. The rat c-maf
      gene is an intronless gene, covering a length of 3.5 kb. Transient transfection
      analysis of the 5'-flanking region of the c-maf gene using luciferase as the
      reporter gene shows that Pax6, a master transcription factor for lens
      development, strongly activates the c-maf promoter construct. Endogenous c-maf is
      also activated by the Pax6 expression vector. Electrophoresis mobility shift
      assay and DNase I footprinting analysis show that at least three Pax6-binding
      sites are located in the 5'-flanking and 5'-non-coding regions of the rat c-maf
      gene. The c-maf gene was also markedly activated by its own product, c-Maf,
      through the MARE (Maf recognition element), suggesting that a positive
      autoregulatory mechanism controls this gene. In situ hybridization histochemical
      detection of Pax6 and c-Maf in the E14 lens showed that both mRNAs are expressed
      in the lens equator where lens epithelial cells are differentiating to lens fiber
      cells. These results suggest that a Pax6/c-Maf transcription factor cascade is
      working in lens development.

PMID- 11222776
TI  - Pituitary Ets-1 and GABP bind to the growth factor regulatory sites of the rat
      prolactin promoter.
AB  - Ets factors play a critical role in oncogenic Ras- and growth factor-mediated
      regulation of the proximal rat prolactin (rPRL) promoter in pituitary cells. The
      rPRL promoter contains two key functional Ets binding sites (EBS): a composite
      EBS/Pit-1 element located at -212 and an EBS that co-localizes with the basal
      transcription element (BTE, or A-site) located at -96. Oncogenic Ras exclusively
      signals to the -212 site, which we have named the Ras response element (RRE);
      whereas the response of multiple growth factors (FGFs, EGF, IGF, insulin and TRH)
      maps to both EBSs. Although Ets-1 and GA binding protein (GABP) have been
      implicated in the Ras and insulin responses, respectively, the precise identity
      of the pituitary Ets factors that specifically bind to the RRE and BTE sites
      remains unknown. In order to identify the Ets factor(s) present in GH4 and GH3
      nuclear extracts (GH4NE and GH3NE) that bind to the EBSs contained in the RRE and
      BTE, we used EBS-RRE and BTE oligonucleotides in electrophoretic mobility shift
      assays (EMSAs), antibody supershift assays, western blot analysis of partially
      purified fractions and UV-crosslinking studies. EMSAs, using either the BTE or
      EBS-RRE probes, identified a specific protein-DNA complex, designated complex A,
      which contains an Ets factor as determined by oligonucleotide competition
      studies. Using western blot analysis of GH3 nuclear proteins that bind to heparin
      Sepharose, we have shown that Ets-1 and GABP, which are MAP kinase substrates, co
      purify with complex A, and supershift analysis with specific antisera revealed
      that complex A contains Ets-1, GABPalpha and GABPbeta1. In addition, we show that
      recombinant full-length Ets-1 binds equivalently to BTE and EBS-RRE probes, while
      recombinant GABPalpha/beta preferentially binds to the BTE probe. Furthermore,
      comparing the DNA binding of GH4NE containing both Ets-1 and GABP and HeLa
      nuclear extracts devoid of Ets-1 but containing GABP, we were able to show that
      the EBS-RRE preferentially binds Ets-1, while the BTE binds both GABP and Ets-1.
      Finally, UV-crosslinking experiments with radiolabeled EBS-RRE and BTE
      oligonucleotides showed that these probes specifically bind to a protein of
      approximately 64 kDa, which is consistent with binding to Ets-1 (54 kDa) and/or
      the DNA binding subunit of GABP, GABPalpha (57 kDa). These studies show that
      endogenous, pituitary-derived GABP and Ets-1 bind to the BTE, whereas Ets-1
      preferentially binds to the EBS-RRE. Taken together, these data provide important
      insights into the mechanisms by which the combination of distinct Ets members and
      EBSs transduce differential growth factor responses.

PMID- 11222777
TI  - Escherichia coli strains that allow antibiotic-free plasmid selection and
      maintenance by repressor titration.
AB  - We report the construction of two novel Escherichia coli strains (DH1lacdapD and
      DH1lacP2dapD) that facilitate the antibiotic-free selection and stable
      maintenance of recombinant plasmids in complex media. They contain the essential
      chromosomal gene, dapD, under the control of the lac operator/promoter. Unless
      supplemented with IPTG (which induces expression of dapD) or DAP, these cells
      lyse. However, when the strains are transformed with a multicopy plasmid
      containing the lac operator, the operator competitively titrates the LacI
      repressor and allows expression of dapD from the lac promoter. Thus transformants
      can be isolated and propagated simply by their ability to grow on any medium by
      repressor titration selection. No antibiotic resistance genes or other protein
      expressing sequences are required on the plasmid, and antibiotics are not
      necessary for plasmid selection, making these strains a valuable tool for
      therapeutic DNA and recombinant protein production. We describe the construction
      of these strains and demonstrate plasmid selection and maintenance by repressor
      titration, using the new pORT plasmid vectors designed to facilitate recombinant
      DNA exploitation.

PMID- 11222778
TI  - Isolation of anti-angiogenesis antibodies from a large combinatorial repertoire
      by colony filter screening.
AB  - We describe here a method, based on iterative colony filter screening, for the
      rapid isolation of binding specificities from a large synthetic repertoire of
      human antibody fragments in single-chain Fv configuration. Escherichia coli
      cells, expressing the library of antibody fragments, are grown on a porous master
      filter, in contact with a second filter coated with the antigen, onto which
      antibodies secreted by the bacteria are able to diffuse. Detection of antigen
      binding on the second filter allows the recovery of a number of E.coli cells,
      including those expressing the binding specificity of interest, which can be
      submitted to a second round of screening for the isolation of specific monoclonal
      antibodies. We tested the methodology using as antigen the ED-B domain of
      fibronectin, a marker of angiogenesis. From an antibody library of 7 x 10(8)
      clones, we recovered a number of specifically-binding antibodies of different
      aminoacid sequence. The antibody clone showing the strongest enzyme-linked
      immunosorbent assay signal (ME4C) was further characterised. Its epitope on the
      ED-B domain was mapped using the SPOT synthesis method, which uses a set of
      decapeptides spanning the antigen sequence synthesised and anchored on cellulose.
      ME4C binds to the ED-B domain with a dissociation constant K:(d) = 1 x 10(-7) M
      and specifically stains tumour blood vessels, as shown by immunohistochemical
      analysis on tumour sections of human and murine origin.

PMID- 11222779
TI  - Identification of partial loss of function p53 gene mutations utilizing a yeast
      based functional assay.
AB  - Missense mutations within the central DNA binding region of p53 are the most
      prevalent mutations found in human cancer. Numerous studies indicate that 'hot
      spot' p53 mutants (which comprise approximately 30% of human p53 gene mutations)
      are largely devoid of transcriptional activity. However, a growing body of
      evidence indicates that some non-hot-spot p53 mutants retain some degree of
      transcriptional activity in vivo, particularly against strong p53 binding sites.
      We have modified a previously described yeast-based p53 functional assay to
      readily identify such partial loss of function p53 mutants. We demonstrate the
      utility of this modified p53 functional assay using a diverse panel of p53
      mutants.

PMID- 11222780
TI  - Quantitative analysis of mRNA amplification by in vitro transcription.
AB  - Effective transcript profiling in animal systems requires isolation of homogenous
      tissue or cells followed by faithful mRNA amplification. Linear amplification
      based on cDNA synthesis and in vitro transcription is reported to maintain
      representation of mRNA levels, however, quantitative data demonstrating this as
      well as a description of inherent limitations is lacking. We show that published
      protocols produce a template-independent product in addition to amplifying real
      target mRNA thus reducing the specific activity of the final product. We describe
      a modified amplification protocol that minimizes the generation of template
      independent product and can therefore generate the desired microgram quantities
      of message-derived material from 100 ng of total RNA. Application of a second,
      nested round of cDNA synthesis and in vitro transcription reduces the required
      starting material to 2 ng of total RNA. Quantitative analysis of these products
      on Caenorhabditis elegans Affymetrix GeneChips shows that this amplification does
      not reduce overall sensitivity and has only minor effects on fidelity.

PMID- 11222781
TI  - Time for more attention to migrainous vertigo?

PMID- 11222782
TI  - Improving brain function with transcranial magnetic stimulation?

PMID- 11222783
TI  - The interrelations of migraine, vertigo, and migrainous vertigo.
AB  - OBJECTIVE: To assess the prevalence of migrainous vertigo in patients with
      migraine and in patients with vertigo according to explicit diagnostic criteria
      that are presented for discussion. METHODS: The authors prospectively evaluated
      200 consecutive patients from a dizziness clinic and 200 patients from a migraine
      clinic for migrainous vertigo based on the following criteria: 1) recurrent
      vestibular symptoms (rotatory/positional vertigo, other illusory self or object
      motion, head motion intolerance); 2) migraine according to the criteria of the
      International Headache Society (IHS); 3) at least one of the following migrainous
      symptoms during at least two vertiginous attacks: migrainous headache,
      photophobia, phonophobia, visual or other auras; and 4) other causes ruled out by
      appropriate investigations. In addition, the authors compared the prevalence of
      migraine according to the IHS criteria in the dizziness clinic group with a sex-
      and age-matched control group of 200 orthopedic patients. RESULTS: The prevalence
      of migraine according to the IHS criteria was higher in the dizziness clinic
      group (38%) compared with the age- and sex-matched control group (24%, p < 0.01).
      The prevalence of migrainous vertigo was 7% in the dizziness clinic group, and 9%
      in the migraine clinic group. In 15 of 33 patients with migrainous vertigo,
      vertigo was regularly associated with migrainous headache. In 16 patients,
      vertigo occurred both with and without headache, and in two patients headache and
      vertigo never occurred together. The duration of attacks varied from minutes to
      days. CONCLUSION: These results substantiate the epidemiologic association
      between migraine and vertigo and indicate that migrainous vertigo affects a
      significant proportion of patients both in dizziness and headache clinics.

PMID- 11222784
TI  - Quality of life in ALS is maintained as physical function declines.
AB  - OBJECTIVES: To study patients with ALS to determine how physical function,
      quality of life (QOL), and spirituality or religiousness change over time, and
      what relationship these changes have to one another. METHODS: Sixty patients with
      ALS were studied prospectively. They were assessed at baseline, 3 months, and 6
      months, using questionnaires designed to measure general quality of life (McGill
      Quality of Life questionnaire), religiosity (Idler Index of Religiosity), ALS
      specific health-related quality of life (SIP/ALS-19), and ALS-specific function
      (ALS functional rating scale). RESULTS: A two-way repeated measures multivariate
      analysis of variance revealed that both the passage of time and the specific QOL
      scales used were factors in predicting patient quality of life (F[1, 59]= 9.87, p
      < 0.003 and F[3, 177]= 16.90, p < 0.001) Despite a progressive decline in
      physical function as measured by the ALS-specific function score, the general QOL
      and religiosity scores changed little. In contrast, the ALS-specific health
      related QOL score declined in parallel with the ALS-specific function score.
      CONCLUSIONS: QOL in patients with ALS appears to be independent of physical
      function, which agrees with a previous cross-sectional study. The ALS-specific
      health-related QOL score is primarily a measure of physical function. QOL
      instruments that assess spiritual, religious, and psychological factors produce
      different results than those obtained using measures of physical function alone.

PMID- 11222785
TI  - Randomized controlled trial of IVIg in untreated chronic inflammatory
      demyelinating polyradiculoneuropathy.
AB  - OBJECTIVE: To determine the efficacy of IV immunoglobulin (IVIg) given patients
      with untreated chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).
      METHODS: A randomized, double-blind, multicenter, investigator-initiated study
      compared IVIg (Aventis Behring LLC, King of Prussia, PA) with placebo (5%
      albumin). On days 1, 2, and 21, IVIg (1 g/kg) or placebo was given. The primary
      outcome measure was the change in muscle strength from baseline to day 42, using
      the average muscle score (AMS). Secondary outcome measures included change from
      baseline AMS at days 10 and 21, the Hughes' functional disability scale, forced
      vital capacity (FVC), and nerve conduction studies (NCS) of four motor nerves
      (median, ulnar, peroneal, and tibial). RESULTS: The patients (n = 33) were
      randomized. Of these, 30 (14 women, 16 men, aged 54 +/- 20 years, range 13 to 82)
      received IVIg and 23 were given placebo (12 women, 11 men, aged 50 +/- 18 years,
      range 23 to 73). Baseline AMS values of the groups were similar (IVIg 7.06 +/-
      1.31 versus placebo 7.28 +/- 1.18, p = 0.53). There were two dropouts in placebo
      group and one in the IVIg group. Mean AMS improved at day 42 comparing IVIg with
      placebo (0.63 versus -0.1, p = 0.006). Improved strength was seen by day 10. The
      placebo group lost strength over this same interval. In the IVIg, 11 subjects
      improved by the functional disability scale; none worsened. This differed (p =
      0.019) from those in the placebo-treated group (two improved, two got worse,
      remainder unchanged). Forced vital capacity did not improve with IVIg treatment.
      IVIg improved ulnar motor distal latency (p = 0.005), tibial distal compound
      muscle amplitude (p = 0.003), and peroneal nerve conduction velocity (p = 0.03).
      CONCLUSIONS: IVIg improves strength in patients with untreated CIDP by day 10
      with continued benefit through day 42; more than one third improve by at least a
      functional grade on a disability scale. This study provides data supporting IVIg
      as the initial treatment for CIDP.

PMID- 11222786
TI  - Autosomal dominant limb-girdle muscular dystrophy: a large kindred with evidence
      for anticipation.
AB  - BACKGROUND: Fourteen genetically distinct forms of limb-girdle muscular dystrophy
      (LGMD) have been identified, including five types of autosomal dominant LGMD (AD
      LGMD). OBJECTIVE: To describe clinical, histologic, and genetic features of a
      large Spanish kindred with LGMD and apparent autosomal dominant inheritance
      spanning five generations. METHOD: The authors examined 61 members of the family;
      muscle biopsies were performed on five patients. Linkage analysis assessed
      chromosomal loci associated with other forms of AD-LGMD. RESULTS: A total of 32
      individuals had weakness of the pelvic and shoulder girdles. Severity appeared to
      worsen in successive generations. Muscle biopsy findings were nonspecific and
      compatible with MD. Linkage analysis to chromosomes 5q31, 1q11-q21, 3p25, 6q23,
      and 7q demonstrated that this disease is not allelic to LGMD forms 1A, 1B, 1C,
      1D, and 1E. CONCLUSIONS: This family has a genetically distinct form of AD-LGMD.
      The authors are currently performing a genome-wide scan to identify the disease
      locus.

PMID- 11222788
TI  - New mutation (R42P) of the parkin gene in the ubiquitinlike domain associated
      with parkinsonism.
AB  - OBJECTIVE: To investigate the association between parkin gene mutations and
      parkinsonism in an Italian family in which three of 12 siblings born to first
      degree consanguineous parents had early-onset parkinsonism. BACKGROUND: Several
      deleting or truncating mutations as well as missense mutations of the parkin gene
      were associated with early-onset parkinsonism. METHOD: Three brothers were
      examined clinically at several stages of the disease. Single-strand
      conformational polymorphism analysis was done on the parkin gene of 32 members of
      the family. Samples showing mobility shifts were considered for mutation
      analysis. RESULTS: Direct DNA sequencing revealed a novel homozygous amino acid
      substitution, Arg42Pro, in all three patients compared with a control DNA sample.
      The mutation occurred in the ubiquitinlike domain at the N-terminal of the
      protein. The patients did not display the clinical hallmarks previously seen with
      parkin mutations and were indistinguishable from patients with sporadic PD.
      CONCLUSIONS: These findings confirm the recessive character of parkin mutations
      causing early-onset parkinsonism and the essential role of the ubiquitinlike
      region, highly conserved among species, and in accordance with the proposed
      parkin function.

PMID- 11222789
TI  - Paraplegin gene analysis in hereditary spastic paraparesis (HSP) pedigrees in
      northeast England.
AB  - OBJECTIVE: To identify the frequency and characterize the phenotype of paraplegin
      mutations in the hereditary spastic paraparesis (HSP) population in the northeast
      of England. BACKGROUND: HSP is a disorder that shows both clinical and genetic
      heterogeneity. To date, 13 loci have been associated with an HSP phenotype, with
      the causative gene having been identified in four of these. Two autosomal genes
      have been identified, paraplegin and spastin, and two X-linked genes have been
      identified, L1CAM (cell adhesion molecule) and proteolipid protein. METHODS:
      Thirty HSP pedigrees from the northeast of England were analyzed for mutation in
      each of the 17 exons of the paraplegin gene. RESULTS: A single family with a
      paraplegin mutation was identified in which the paraplegin mutation co-segregates
      with an HSP phenotype in an apparent dominant manner. The authors also describe
      frequent polymorphism in the paraplegin gene in both the HSP and control
      populations. CONCLUSION: Mutations in the paraplegin gene are not a common cause
      of HSP in the northeast of England. The phenotype of the paraplegin-related HSP
      family described had several striking features including amyotrophy, raised
      creatine kinase, sensorimotor peripheral neuropathy, and oxidative
      phosphorylation defect on muscle biopsy.

PMID- 11222787
TI  - A randomized, controlled trial of remacemide for motor fluctuations in
      Parkinson's disease.
AB  - BACKGROUND: Preclinical studies suggest that glutamate antagonists help
      ameliorate motor fluctuations in patients with PD treated with levodopa. METHODS:
      In a multicenter, randomized, double-blind, placebo-controlled, parallel-group,
      dose-ranging study, the authors assessed the safety, tolerability, and efficacy
      of the glutamate receptor blocker remacemide hydrochloride in 279 patients with
      motor fluctuations treated with levodopa. The primary objective was to assess the
      short-term tolerability and safety of four dosage levels of remacemide during 7
      weeks of treatment. Patients were also monitored with home diaries and the
      Unified PD Rating Scale (UPDRS) to collect preliminary data on treatment
      efficacy. RESULTS: Remacemide was well tolerated up to a dosage of 300 mg/d on a
      twice daily schedule and 600 mg/d on a four times daily schedule. The most common
      dosage-related adverse events were dizziness and nausea, as observed in previous
      studies of remacemide. The percent "on" time and motor UPDRS scores showed trends
      toward improvement in the patients treated with 150 and 300 mg/d remacemide
      compared with placebo-treated patients, although these improvements were not
      significant. CONCLUSION: Remacemide is a safe and tolerable adjunct to
      dopaminergic therapy for patients with PD and motor fluctuations. Although this
      study had limited power to detect therapeutic effects, the observed improvement
      is consistent with studies of non-human primates with 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine-induced parkinsonian signs and symptoms. Additional studies
      are warranted to confirm these results over an extended period of observation,
      and to explore the potential neuroprotective effects of remacemide in slowing the
      progression of PD.

PMID- 11222790
TI  - The functional anatomy of gaze-evoked tinnitus and sustained lateral gaze.
AB  - OBJECTIVE: To identify neural sites associated with gaze-evoked tinnitus (GET),
      an unusual condition that may follow cerebellar-pontine angle surgery. METHODS:
      The authors examined eight patients with GET and used PET to map the neural sites
      activated by lateral gaze in them and seven age- and sex-matched control
      subjects. RESULTS: In patients with GET, tinnitus loudness and pitch increased
      with lateral gaze and, to a lesser extent, up and down gaze. Evidence for neural
      activity related to GET was seen in the auditory lateral pontine tegmentum or
      auditory cortex. GET-associated nystagmus appears to activate the cuneus and
      cerebellar vermis. These sites were found in addition to an extensive network
      that included frontal eye fields and other sites in frontal, parietal, and
      temporal cortex that were activated by lateral gaze in seven control subjects and
      the patients. The unilateral deafness in patients with GET was associated with
      expansion of auditory cortical areas responsive to tones delivered to the good
      ear. In addition to GET, unilateral deafness, end-gaze nystagmus, and facial
      nerve dysfunction were common. CONCLUSIONS: Patients with GET have plastic
      changes in multiple neural systems that allow neural activity associated with eye
      movement, including those associated with the neural integrator, to stimulate the
      auditory system. Anomalous auditory activation is enhanced by the failure of
      cross-modal inhibition to suppress auditory cortical activity. The time course
      for the development of GET suggests that it may be due to multiple mechanisms.

PMID- 11222791
TI  - MRI identification of early white matter injury in anoxic-ischemic
      encephalopathy.
AB  - BACKGROUND: Anoxic-ischemic encephalopathy (AIE) affects the gray matter more
      than the white matter. Recent animal experiments suggest that the white matter is
      more sensitive to ischemia than previously thought. The authors describe the MRI
      findings in seven patients with AIE who demonstrate early preferential
      involvement of the white matter. MATERIALS AND METHODS: A retrospective case
      series study was performed, including seven patients with AIE who underwent MRI
      of the brain within 7 days of insult. Demographic information, type of insult,
      clinical examination findings, EEG findings, and clinical outcome were obtained.
      MRI studies were reviewed with specific attention to the cortex, deep gray
      matter, and the white matter structures. Mean apparent diffusion coefficient
      (ADC) was calculated in regions of interest placed in the cerebellar hemispheres,
      putamen, thalamus, splenium of corpus callosum, centrum semiovale, and medial
      frontal cortex. RESULTS: The causes of AIE were cardiac arrhythmias in two
      patients, myocardial infarction in one, drug overdose in two, carbon monoxide
      poisoning in one, and respiratory failure and sepsis in one. The median time to
      MRI was 2.5 days. Symmetric areas of restricted diffusion were found in the
      periventricular white matter tracts (7/7 patients), the corpus callosum (6/7
      patients), internal capsule (5/7 patients), and the subcortical association
      fibers (3/7 patients). ADC maps confirmed the restricted diffusion. Gray matter
      involvement was seen in three patients, and was more prominent on conventional
      imaging sequences compared with diffusion-weighted imaging. A subtle decrease in
      mean ADC was seen in cortex. CONCLUSIONS: Prominent, symmetric restricted
      diffusion can occur early after AIE in white matter, whereas gray matter
      involvement may be less prominent. Further studies involving a larger sample and
      serial imaging are required to confirm these preliminary findings.

PMID- 11222792
TI  - Neuropathology in vegetative and severely disabled patients after head injury.
AB  - OBJECTIVE: To discover if the neuropathology differs in head-injured patients who
      were in a vegetative state (VS) or were severely disabled at time of death.
      METHODS: Review of 35 VS cases and 30 severely disabled cases treated in this
      institute in the acute stage, surviving at least a month; all brains were fixed
      for 3 weeks before full neuropathologic examination. RESULTS: The severely
      disabled cases were older, had a higher incidence of skull fracture and of
      evacuated intracranial hematoma, and they had more cortical contusions. Diffuse
      axonal injury (DAI) was less common in the severely disabled cases, particularly
      its most severe grade. Structural damage in the thalamus was much less common in
      severely disabled cases. Half of the severely disabled patients had neither grade
      2 or 3 DAI nor thalamic damage and 10 of these 15 cases did not have ischemic
      brain damage either. These combinations did not occur in a single VS case.
      However, some severely disabled cases had similar lesions to VS cases, and this
      included some patients who were in a minimally conscious state as well as some
      who were out of bed and mobile. CONCLUSIONS: Half the severely disabled cases had
      only focal brain damage, a feature not found in any VS cases. In the severely
      disabled patients with lesions similar to those of VS cases it is likely that a
      greater quantitative amount of damage occurred in the VS cases.

PMID- 11222793
TI  - Association of a 27-bp repeat polymorphism in ecNOS gene with ischemic stroke in
      Chinese patients.
AB  - OBJECTIVE: To investigate the association between a 27-bp repeat polymorphism of
      the ecNOS gene in 364 patients with ischemic stroke and 516 control subjects.
      BACKGROUND: The incidence of stroke in China is higher than that of coronary
      artery disease. Furthermore, ischemic stroke is more prevalent than hemorrhagic
      stroke. A 27-bp repeat polymorphism in intron 4 of the endothelial constitutive
      nitric oxide synthase (ecNOS) gene has been reported to associate with coronary
      artery disease in an Australian population, but no association was found between
      this polymorphism and ischemic stroke in a Japanese population. METHODS: All
      patients and unrelated control subjects were screened by CT. All participants
      lived in central China. Multivariate logistic regression analysis was used to
      determine the independent roles of this ecNOS gene polymorphism and covariates in
      ischemic stroke. RESULTS: These results indicated an association between the
      ecNOS a allele and ischemic stroke in the Chinese patients studied (7.8 versus
      17.0%; OR = 2.44; 95% CI = 1.60 to 3.71, p < 0.0001). CONCLUSION: The ecNOS a
      allele in intron 4 may be an independent risk factor for ischemic stroke in the
      Chinese population studied, especially in those lacking other conventional risk
      factors.

PMID- 11222794
TI  - Embolism in acute middle cerebral artery stenosis.
AB  - OBJECTIVE: To investigate the frequency of middle cerebral artery (MCA) stenosis
      in a series of nonselected patients and the coexistence of microembolic signals
      with stenosis. METHODS: MCA stenosis was sought by transcranial Doppler (TCD) in
      387 patients admitted consecutively with acute ischemic cerebrovascular disease
      within the first 48 hours of the onset of symptoms and again at 6 months. TCD
      monitoring for microembolic signals was performed on all patients with MCA
      stenosis. RESULTS: MCA stenoses were found in 29 patients (7%), although in only
      20 patients (5%) was the stenosis symptomatic. Microembolic signals were detected
      in five of 14 symptomatic stenoses (36%) monitored at the acute phase, but none
      were found in the chronic phase or in asymptomatic stenosis. Despite one third of
      symptomatic patients having had a further source of emboli, microembolic signals
      were detected only distally to the MCA stenosis. In the symptomatic group, 25% of
      stenoses had completely disappeared 6 months after stroke. Microembolic signal
      detection at the acute phase was associated with the subsequent disappearance of
      the stenosis. CONCLUSIONS: The frequency of symptomatic MCA stenosis in acute
      ischemic stroke was 5% in the population studied. Many stenoses are transient,
      and microembolic signals are often detectable at the poststenotic segment in the
      acute phase. The origin of at least 25% of symptomatic acute MCA stenoses may be
      embolic rather than atherosclerotic.

PMID- 11222795
TI  - Assessment of aspiration risk in stroke patients with quantification of voluntary
      cough.
AB  - BACKGROUND: Dysphagia and subsequent aspiration are serious complications of
      acute stroke that may be related to an impaired cough reflex. It was hypothesized
      that aspirating stroke patients would have impaired objective measures of
      voluntary cough as compared with both nonstroke control subjects and
      nonaspirating stroke patients. METHODS: Swallowing was evaluated by standard
      radiologic or endoscopic methods, and stroke patients were grouped by aspiration
      severity (severe, n = 11; mild, n = 17; no aspiration, n = 15). Airflow patterns
      and sound pressure level (SPL) of voluntary cough were measured in stroke
      patients and in a group of normal control subjects (n = 18). Initial stroke
      severity was determined retrospectively with the Canadian Neurological Scale.
      RESULTS: All cough measures were altered in stroke patients as a group relative
      to nonstroke control subjects. Univariate analysis showed that peak flow of the
      inspiration phase (770.6 +/- 80.6 versus 1,120.1 +/- 148.4 mL/s), SPL (90.0 +/-
      3.1 versus 100.2 +/- 1.6 dB), peak flow of the expulsive phase (875.1 +/- 122.7
      versus 1,884.1 +/- 221.6 mL/s), expulsive phase rise time (0.34 +/- 0.1 versus
      0.09 +/- 0.01 s), and cough volume acceleration (5.5 +/- 1.3 versus 27.8 +/- 3.9
      mL/s/s) were significantly impaired in severe aspirators as compared with
      nonaspirators. Aspirating patients had more severe strokes than nonaspirators
      (mean Canadian Neurological Scale score 7.7 +/- 0.7 versus 9.8 +/- 0.3).
      Multivariate logistic regression found only expulsive phase rise time values
      during cough correlated with aspiration status. CONCLUSION: Objective analysis of
      cough may provide a noninvasive way to identify the aspiration risk of stroke
      patients.

PMID- 11222796
TI  - MS and neuromyelitis optica in Martinique (French West Indies).
AB  - BACKGROUND AND OBJECTIVE: A population-based study is reported of MS in French
      Afro-Caribbeans (FAC) in Martinique. FAC are descendants of interracial mating
      that occurred between French Caucasians and black Africans in the 17th and the
      18th centuries. METHODS: The authors surveyed the entire island of Martinique
      (area 1,128 km(2), population 357,000) between November 1997 and October 1999.
      RESULTS: Sixty-two patients (46 females, 16 males, ratio 2.9:1) were identified
      with definite or probable disease by the Poser criteria. Prevalence for all
      patients on December 31, 1998, was 17.4/10(5) (95% CI 13.1 to 21.7) and
      14.3/10(5) (95% CI 10.4 to 18.2) for clinically definite cases (n = 51). Age
      range of patients on prevalence day was 17 to 73 years (mean +/- SD 39 +/- 11.3
      years). Mean age at onset was 31.2 +/- 11 years. Overall, 9.7% had primary
      progressive disease and 19.4% had benign MS. A low proportion of definite and
      probable MS cases had oligoclonal bands in CSF (50.9%). Seventeen patients, 13 of
      whom were alive on prevalence day, had a relapsing form of neuromyelitis optica.
      CONCLUSION: The island of Martinique appears to have a low to medium prevalence
      of MS. MS was almost unknown in FAC in Martinique until the late 1970s. The
      apparent recent increase may be explained by improved recognition of patients,
      increased availability of MRI for diagnosis, increased disease awareness among
      physicians, increased survival of MS patients, or an actual increase in disease
      frequency.

PMID- 11222797
TI  - Mortality in antiepileptic drug development programs.
AB  - BACKGROUND: Pooled data from New Drug Applications (NDAs) submitted to the U.S.
      Food and Drug Administration (FDA) provide an opportunity to study the incidence
      of and risk factors for rare events. OBJECTIVE: To examine the incidence and
      causes of mortality in patients with epilepsy participating in clinical trials of
      antiepileptic drugs (AEDs); and to examine the incidence of and risk factors for
      sudden unexplained death in such patients. METHODS: Exposure data and death
      narratives were obtained from the NDAs of five recently reviewed AEDs. Deaths
      were classified as sudden unexplained, accidental, or other cause using the 1993
      Burroughs-Wellcome expert panel criteria, and mortality rates were calculated for
      each category. Add-on trials were analyzed separately from monotherapy initiation
      trials. RESULTS: Among 9,144 patients in the add-on trial database, the all-cause
      and sudden unexplained mortality rates were 9.1 and 3.8 deaths per 1,000 person
      years (124 and 52 deaths in 13,617.1 person-years of drug exposure). Sixty-five
      percent of all deaths were related to the underlying epilepsy. Of the examined
      risk factors, only age was associated with the incidence of sudden unexplained
      death. Among 1,293 patients in the monotherapy initiation trials, the all-cause
      and sudden unexplained mortality rates were 7.1 and 0 deaths per 1,000 person
      years (7 and 0 deaths in 982.5 person-years of drug exposure). CONCLUSIONS: A
      large proportion of the deaths in the add-on cohort was attributable to epilepsy
      related causes. Mortality due to sudden death in the add-on cohort falls into the
      high end of the reported range for patients with epilepsy. The difference in
      mortality due to sudden death between the add-on and monotherapy initiation
      cohorts suggests that disease severity is the primary determining factor for risk
      of sudden unexplained death.

PMID- 11222798
TI  - Incidence and risk factors in sudden unexpected death in epilepsy: a prospective
      cohort study.
AB  - OBJECTIVE: To determine incidence of and risk factors for sudden unexpected death
      in epilepsy (SUDEP). METHODS: Three epilepsy centers enrolled 4,578 patients and
      prospectively followed these patients for 16,463 patient-years. The cohort was
      screened for death annually. Deaths were investigated to determine whether SUDEP
      occurred. Potential risk factors were compared in SUDEP cases and in controls
      enrolled contemporaneously at the same center. RESULTS: Incidence of SUDEP was
      1.21/1,000 patient-years and was higher among women (1.45/1,000) than men
      (0.98/1,000). SUDEP accounted for 18% of all deaths. Occurrence of tonic-clonic
      seizures, treatment with more than two anticonvulsant medications, and full-scale
      IQ less than 70 were independent risk factors for SUDEP. The number of tonic
      clonic seizures was a risk factor only in women. The presence of cerebral
      structural lesions and use of psychotropic drugs at the last visit were not risk
      factors for SUDEP in this cohort. Subtherapeutic anticonvulsant levels at the
      last visit were equally common in the two groups. No particular anticonvulsant
      appeared to be associated with SUDEP. CONCLUSIONS: These results support the idea
      that tonic-clonic seizures are an important proximate cause of SUDEP. This
      information creates a risk profile for SUDEP that may help direct preventative
      efforts.

PMID- 11222799
TI  - Enhancing analogic reasoning with rTMS over the left prefrontal cortex.
AB  - The authors utilized repetitive transcranial magnetic stimulation (rTMS) in 16
      normal volunteers to investigate the role of the left dorsolateral prefrontal
      cortex (PFC) in analogic reasoning. rTMS over the left and right PFC, over the
      left motor cortex, and sham stimulation over the left PFC were administered
      during memory and analogic reasoning conditions. rTMS over the left PFC led to a
      significant reduction in response times only in the analogy condition without
      affecting accuracy. These results indicate that the left PFC is relevant for
      analogic reasoning and that rTMS applied to the PFC can speed up solution time.

PMID- 11222800
TI  - Antibodies to brain antigens following stroke.
AB  - Cerebral necrosis following stroke exposes brain antigens to the immune system,
      potentially initiating an antibody response. The authors measured levels of
      antibodies to specific neuronal antigens, neurofilaments (NF), and a ubiquitous
      antigen, cardiolipin (CL), in 45 patients following an acute first-ever stroke,
      within 48 hours, and 1, 3, and 6 months later. The mean levels of anti-NF
      antibodies were elevated compared with baseline at 1, 3, and 6, months (p =
      0.012, 0.002, and 0.003 by paired t-test). Anti-CL levels did not change
      significantly.

PMID- 11222801
TI  - Suppression of recurrent transient ischemic attacks by a statin agent.
AB  - Recent studies of hydroxy-methylglutaryl coenzyme A reductase inhibitors have
      demonstrated that therapy with statins is associated with a significant decrease
      in the risk of stroke and TIA in patients with coronary artery disease. The
      underlying mechanism responsible for this effect is unclear. The author presents
      two patients who had cessation of TIAs upon institution of statin therapy. A
      variety of non-lipid-lowering mechanisms may account for this beneficial effect.
      This initial observation, if confirmed by further study, may suggest a role for
      statin agents in preventing recurrent TIAs.

PMID- 11222802
TI  - Asterixis after unilateral stroke: lesion location of 30 patients.
AB  - The author describes 30 consecutive patients with unilateral stroke who had
      asterixis on presentation. The lesion location was as follows: thalamus in 19
      (mostly, ventrolateral nucleus), frontal lobe in six, lenticulocapsular area in
      one, midbrain in two, and the cerebellum in two patients. Four patients had
      bilateral asterixis, and two patients with cerebellar lesions had ipsilateral
      asterixis. The asterixis may be caused by the abnormal control of arm posture
      maintenance due to functional dysregulation of the brainstem-spinal tracts from
      the cerebello-brainstem-thalamo-frontal lobe system.

PMID- 11222803
TI  - Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston
      criteria.
AB  - The authors performed clinical-pathologic correlation to assess the validity of
      the Boston diagnostic criteria for cerebral amyloid angiopathy (CAA). Thirteen
      subjects were diagnosed clinically with probable CAA from among 39 patients with
      available pathologic tissue in a prospective cohort of subjects aged > or = 55
      years with primary lobar hemorrhage. All 13 individuals were confirmed
      neuropathologically as having CAA. This small pathologic series indicates that
      the diagnosis of probable CAA can be made during life with high accuracy.

PMID- 11222804
TI  - CCM1 gene mutations in families segregating cerebral cavernous malformations.
AB  - Cerebral cavernous malformations (CCM) are vascular anomalies, sometimes
      inherited as an autosomal dominant trait, which can cause strokes and seizures.
      Recently, mutations of the CCM1 gene (chromosome 7q) have been found in a subset
      of families. The authors found 10 new mutations by screening 29 families and five
      seemingly sporadic cases of CCM. The mutations predicted truncation of the Krit1
      mRNA encoded by CCM1, supporting the contention that CCM result from loss of
      Krit1 protein function and the possibility that this protein acts as a tumor
      suppressor.

PMID- 11222805
TI  - Diffusion tensor brain MR imaging in X-linked cerebral adrenoleukodystrophy.
AB  - Brain diffusion tensor MRI of 11 boys with X-linked adrenoleukodystrophy was
      performed. The authors determined quantitative isotropic apparent diffusion
      coefficient (ADC(i)) and fractional anisotropy (FA) values in the white matter.
      ADC(i) and FA values in the affected white matter were significantly different
      from those in normal-appearing white matter. Zonal ADC(i) and FA gradations,
      which might originate from well-established histopathologic zonal changes,
      existed within affected white matter.

PMID- 11222807
TI  - Deep brain stimulation of the subthalamic nucleus: clinical effectiveness and
      safety.
AB  - The authors report the data relative to the clinical effectiveness of bilateral
      deep brain stimulation of the subthalamic nucleus in 16 patients with PD 3 months
      after the surgery. The comparison of the Unified PD Rating Scale scores in the
      different conditions of medication and stimulation, and the lack of significant
      surgical complications, confirm the effectiveness and the safety of the
      subthalamic nucleus deep brain stimulation for the treatment of advanced PD.

PMID- 11222806
TI  - Safety and efficacy of pallidal or subthalamic nucleus stimulation in advanced
      PD.
AB  - The authors retrospectively compared 1-year results of bilateral deep brain
      stimulation (DBS) of the subthalamic nucleus (STN; n = 16) and internal pallidum
      (GPi) (n = 11) in advanced PD and found about equal improvements in "off" period
      motor symptoms, dyskinesias, and fluctuations. STN stimulation reduced medication
      requirements by 65% and required significantly less electrical power. These
      advantages contrasted with a need for more intensive postoperative monitoring and
      a higher incidence of adverse events related to levodopa withdrawal.

PMID- 11222808
TI  - Clinical and pathologic abnormalities in a family with parkinsonism and parkin
      gene mutations.
AB  - A Dutch family with autosomal recessive early-onset parkinsonism showed a
      heterozygous missense mutation in combination with a heterozygous exon deletion
      in the parkin gene. Although the main clinical syndrome consisted of
      parkinsonism, the proband clinically had additional mild gait ataxia and
      pathologically showed neuronal loss in parts of the spinocerebellar system, in
      addition to selective loss of dopaminergic neurons in the substantia nigra pars
      compacta. Lewy bodies and neurofibrillary tangles were absent, but tau pathology
      was found.

PMID- 11222809
TI  - Machado-Joseph disease associated with an absence of fungiform papillae on the
      tongue.
AB  - The authors report the case of a family with Machado-Joseph disease (MJD)
      associated with sensory and autonomic disturbances-particularly the absence of
      fungiform papillae on the tongue and taste buds. Sural nerve biopsy showed a loss
      of myelinated fibers. Autonomic function tests showed bladder-bowel dysfunction,
      hypohidrosis, and low coefficients of variation of R-R intervals on
      electrocardiogram. These findings may be another possible variant or previously
      unrecognized symptoms in MJD.

PMID- 11222810
TI  - Changes in referral pattern and its effect on outcome in patients with Guillain
      Barre syndrome.
AB  - The authors assessed the referral pattern and outcome in patients with Guillain
      Barre syndrome (n = 266) after the introduction of intravenous immunoglobulin
      (IVIg). Fewer patients were transferred from small to large hospitals after the
      introduction of IVIg (p = 0.05). This did not result in a worse outcome in
      patients treated in small centers. The introduction of IVIg has led to a better
      use of different levels of health care facilities.

PMID- 11222811
TI  - Myocardial injury after hemorrhage into the lateral medulla oblongata.

PMID- 11222812
TI  - Deterioration following improvement with tPA therapy: carotid thrombosis and
      reocclusion.

PMID- 11222813
TI  - Acute periaqueductal syndrome associated with the G11778A mitochondrial DNA
      mutation.

PMID- 11222814
TI  - Sudden sensorineural hearing loss associated with herpes simplex virus type 1
      infection.

PMID- 11222815
TI  - In myasthenia gravis cells from atrophic thymus secrete acetylcholine receptor
      antibodies.

PMID- 11222816
TI  - Practice parameter: evaluating a first nonfebrile seizure in children: Report of
      the Quality Standards Subcommittee of the American Academy of Neurology, the
      Child Neurology Society, and the American Epilepsy Society.

PMID- 11222817
TI  - Cervical dural sac and spinal cord in juvenile muscular atrophy of distal upper
      extremity.

PMID- 11222818
TI  - Developmental apraxia arising from neonatal brachial plexus palsy.

PMID- 11222819
TI  - Decreased CSF amyloid beta42 and normal tau levels in dementia with Lewy bodies.

PMID- 11222820
TI  - Changing practice in health care.

PMID- 11222821
TI  - Use of the diagnostic bacteriology laboratory: a practical review for the
      clinician.

PMID- 11222824
TI  - Is wine good for your heart? A critical review.

PMID- 11222823
TI  - Thrombolysis in acute ischaemic stroke.
AB  - In conclusion, thrombolysis with rtPA given within six hours of the onset of
      stroke in carefully selected patients is a safe therapy. However, efficacy has
      only been demonstrated within three hours after stroke onset. At present, only 6%
      12% of all stroke patients are likely to be eligible for thrombolysis. Improved
      methods for investigating acute stroke, particularly magnetic resonance
      techniques, may improve the appropriate targeting of this treatment to those
      patients most likely to benefit. What is certain is that any increasing use of
      thrombolysis will have major effects on stroke services. The emphasis will have
      to be on early assessment and referral, if only to reach an imaging facility for
      a treatment decision to be made.

PMID- 11222825
TI  - Sarcoidosis 2001.
AB  - In every decade, sarcoidosis makes a chameleon-like change so its profile needs
      to be updated. It was first recognised as a dermatological curiosity which
      evolved into a multisystem disorder with bone cysts, uveitis, and intrathoracic
      involvement. New dimensions were uncovered by biochemistry and immunology,
      bringing it still nearer the elusive enigma, namely the cause of sarcoidosis.
      Aetiology includes an understanding of a genetic predisposition and environmental
      trigger factors. What was left undone in the 20th century will become evident in
      the 21st century with more sophisticated technology. Likewise, conventional
      treatments of the past will be superseded by cytokines and other magic bullets of
      the millennium.

PMID- 11222822
TI  - Pregnancy in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly
      affects women of reproductive age. Pregnancy and its outcome is a major concern
      to most SLE patients. Queries regarding the risk of disease flares during
      pregnancy, chance of fetal loss, and the safety of various drugs are often
      raised. With the improvement in the understanding of the pathogenesis of SLE and
      the judicious use of immunosuppressive drugs, better disease control can now be
      achieved and SLE patients should not be deprived of the opportunity for bearing
      children. Prepregnancy counselling and close collaboration with other specialists
      such as the obstetricians and the perinatologists is essential in optimising the
      maternal and fetal outcome in lupus pregnancies. In this review, important issues
      regarding the fertility rate, optimal timing of conception, risk of disease
      flares during lupus pregnancy, pregnancy course, fetal outcome, safety of various
      drugs used for disease control during pregnancy and lactation, and contraceptive
      advice are discussed.

PMID- 11222826
TI  - Evaluation of local invasion by oesophageal carcinoma--a prospective study of
      prone computed tomography scanning.
AB  - The aim of this study was to assess the value of prone computed tomography
      compared with the traditional supine position, in the assessment of invasion of
      adjacent mediastinal structures by oesophageal cancer. A prospective, single
      blind case-case comparative study of signs of local tumour invasion was
      conducted. Sixty nine consecutive patients undergoing computed tomography for
      preoperative staging of oesophageal carcinoma were studied. Computed tomography
      scanning of the thorax was performed in the standard supine followed by prone
      position; in 39 patients the computed tomography findings were correlated with
      the surgical findings. Four established radiological signs used to assess
      mediastinal invasion were scored in each case. Based on the radiological scoring
      system, there was a significant down staging in the probability of aortic
      invasion in 12 of the 69 cases (p<0.05). A similar improvement in accuracy was
      seen in the cases undergoing surgery; of the 38 cases who did not have aortic
      invasion at operation, 10 cases were scored as high for aortic invasion on the
      supine scans compared with only three on the prone position (p<0.05). Prone
      scanning was not of significant additional value in the assessment of major
      airway or pericardial invasion. Modification of the computed tomography protocol
      to include scanning in the prone position will improve the accuracy of the
      preoperative staging of patients with oesophageal malignancy and reduce the
      chance of overstaging disease. Especially in centres where endoscopic ultrasound
      is not available, our modification may reduce the chance of denying patients
      potentially curative operations.

PMID- 11222828
TI  - Evolution of an inguinal hernia surgery practice.
AB  - BACKGROUND: Inguinal hernia surgery has undergone numerous advances in the last
      few years. This study analysed the changes in the practice of one surgeon in a
      district general hospital over a seven year interval. The effect of changing from
      Bassini to Lichtenstein repair in 1994 was evaluated. METHODS: The study involved
      two parts: first a search of a computerised database of inguinal hernia
      procedures, and second, postal audits of men who had an inguinal hernia repair in
      1993 and 1994 with outpatient follow up for those with a possible recurrence.
      RESULTS: A total of 1037 hernias were repaired over the seven years. There was an
      increase in the proportion of day cases from 18% to 70% and the number of
      operations performed under local anaesthetic rose from 1% to 45%. The postal
      audits had response rates of 79% (1993) and 66% (1994). Some 5/98 (5%) recurrent
      hernias were identified from the 1993 (Bassini) patients compared with 1/67
      (1.5%) from the 1994 (Lichtenstein) cohort. CONCLUSION: Lichtenstein hernia
      repair can be performed safely as a day case using local anaesthetic in the
      majority of patients and appears to have a lower recurrence rate than Bassini
      repair.

PMID- 11222827
TI  - Cervical tuberculous lymphadenopathy: changing clinical pattern and concepts in
      management.
AB  - Tuberculosis is one of the biggest health challenges the world is facing. In this
      study the clinical pattern of patients with cervical lymphadenitis, who presented
      to the ear, nose, and throat outpatient department of the Government Medical
      College Hospital, Chandigarh, India between June 1997 and May 1998 is recorded.
      Tuberculosis accounted for 60 out of 94 cases of cervical lymph node enlargement.
      The commonest age group affected was 11-20 years. Constitutional symptoms were
      not present in most of the patients. Multiple matted nodes were seen in 23
      patients but a single discrete node was seen in 18 patients. Upper deep jugular
      nodes were the most commonly affected lymph nodes. Discharging sinus and abscess
      formation were uncommon. Fine needle aspiration cytology yielded a positive
      diagnosis in 52 out of 56 patients. Chest lesions on radiography were evident in
      16% of the patients. Mantoux test was positive and was more than 15 mm in most of
      the patients. This study shows that the classical picture of "scrofula" is no
      longer seen nowadays and can probably be explained by the earlier presentation of
      the disease. All the patients were treated with short course daily chemotherapy
      for six months. Surgery was not required in the majority of patients except in
      four cases where excision biopsy was performed. Patients with abscess formation
      were managed with wide bore needle aspiration only. With a minimum six month
      period of follow up, no patient was found to have a recurrence of local or
      systemic disease. This study emphasises the role of fine needle aspiration
      cytology in diagnosis and confirms the efficacy of six months short course
      chemotherapy.

PMID- 11222829
TI  - Colchicine induced rhabdomyolysis.
AB  - A case of colchicine induced rhabdomyolysis is reported. A 73 year old man with
      ischaemic heart disease, atrial fibrillation, chronic congestive cardiac failure,
      and chronic gout presented with diffuse muscle pain. He had been taking an
      increased dose of colchicine (1.5 mg daily) for an exacerbation of gout for six
      weeks before the presentation. Investigations confirmed the diagnosis of
      rhabdomyolysis and discontinuation of colchicine resulted in resolution of
      clinical and biochemical features of rhabdomyolysis. Although neuromuscular
      adverse effects of colchicine are well recognised, rhabdomyolysis is rare and
      this is only the fourth reported case of colchicine induced rhabdomyolysis in the
      literature.

PMID- 11222830
TI  - Bilateral superselective arterial microcoil embolisation in delayed post
      traumatic high flow priapism.
AB  - High flow arteriogenic priapism is uncommon and usually occurs after trauma to
      the genitoperineal area. The onset of prolonged erection can be delayed and is
      often relatively pain free. Arteriography in this case illustrated the causative
      bilateral arteriocavernosal fistulae and pseudoaneurysms. Treatment consisted of
      staged bilateral superselective metallic microcoil embolisations, resulting in
      prompt detumescence. There were no complications. The patient had normal erectile
      function six months later. Recent concerns about erectile dysfunction with the
      bilateral use of permanent metallic coils appear to be unfounded.

PMID- 11222831
TI  - Laparoscopic excision of splenic hydatid cyst.
AB  - Hydatid disease of the spleen is a rare condition. The standard treatment is open
      total or partial splenectomy. Recently hand assisted laparoscopic total
      splenectomy for splenic hydatid cyst has been reported. A case is described of
      splenic hydatid cyst in a 45 year old man that was excised laparoscopically; the
      related literature is reviewed.

PMID- 11222832
TI  - Neurovascular lessons from a pair of identical twins with cerebral aneurysms.
AB  - A pair of hypertensive identical twins are reported, one of whom was non
      compliant with her antihypertension medication, and after a subarachnoid
      haemorrhage was found to have multiple cerebral aneurysms. The other asymptomatic
      compliant twin was noted to have only a single small cerebral aneurysm. As both
      identical twins are likely to share the same cerebral vascular architecture it is
      suggested that good control of blood pressure contributed to the cerebral
      vascular integrity of the asymptomatic twin. This is the first report on the role
      of blood pressure in the formation of cerebral aneurysms and provides insights
      for an alternative approach to the controversial management of asymptomatic
      cerebral aneurysms.

PMID- 11222834
TI  - Balancing statistical and clinical significance in evaluating treatment effects.

PMID- 11222833
TI  - Pericardial tamponade caused by Pasteurella multocida infection after a cat bite.
AB  - An unusual case of meningitis and pericardial tamponade caused by Pasteurella
      multocida after a cat bite is reported. The patient was successfully treated by
      antibiotics and pericardiocentesis and made an uneventful recovery from a life
      threatening condition. This case illustrates the potential dangers that can arise
      from a seemingly trivial and commonplace injury.

PMID- 11222835
TI  - Selective angiographic catheterisation for jejunal angiodysplasia.

PMID- 11222836
TI  - A patient with atherosclerosis and livedo reticularis.

PMID- 11222837
TI  - Fever, rash, swollen joints, and sore throat in a young man.

PMID- 11222838
TI  - A rare cause of respiratory failure.

PMID- 11222839
TI  - Refractory seizure with hypokalaemia.

PMID- 11222840
TI  - A complication after internal fixation of fracture.

PMID- 11222849
TI  - Polyploidy and gender dimorphism.

PMID- 11222850
TI  - Variability in the El Nino-Southern Oscillation through a glacial-interglacial
      cycle.
AB  - The El Nino-Southern Oscillation (ENSO) is the most potent source of interannual
      climate variability. Uncertainty surrounding the impact of greenhouse warming on
      ENSO strength and frequency has stimulated efforts to develop a better
      understanding of the sensitivity of ENSO to climate change. Here we use annually
      banded corals from Papua New Guinea to show that ENSO has existed for the past
      130,000 years, operating even during "glacial" times of substantially reduced
      regional and global temperature and changed solar forcing. However, we also find
      that during the 20th century ENSO has been strong compared with ENSO of previous
      cool (glacial) and warm (interglacial) times. The observed pattern of change in
      amplitude may be due to the combined effects of ENSO dampening during cool
      glacial conditions and ENSO forcing by precessional orbital variations.

PMID- 11222851
TI  - Observation of d(x2-y2)-like superconducting gap in an electron-doped high
      temperature superconductor.
AB  - High-resolution angle-resolved photoemission spectroscopy of the electron-doped
      high-temperature superconductor Nd(2-x)Ce(x)CuO4 (x = 0.15, transition
      temperature T(c) = 22 K) has found the quasiparticle signature as well as the
      anisotropic d(x2-y2)-like superconducting gap. The spectral line shape at the
      superconducting state shows a strong anisotropic nature of the many-body
      interaction. The result suggests that the electron-hole symmetry is present in
      the high-temperature superconductors.

PMID- 11222852
TI  - Rapid electron tunneling through oligophenylenevinylene bridges.
AB  - We measured rate constants of thermal, interfacial electron transfer through
      oligophenylenevinylene bridges between a gold electrode and a tethered redox
      species in contact with an aqueous electrolyte using the indirect laser-induced
      temperature jump technique. Analysis of the distance dependence indicates that,
      unlike other bridges studied to date, the rate constants are not limited by
      electronic coupling for bridges up to 28 angstroms long. The energy levels of the
      bridges relative to those of the redox species rule out hopping through the
      bridge. We conclude that, out to 28 angstroms, the transfer is limited by
      structural reorganization and that electron tunneling occurs in less than 20
      picoseconds, suggesting that oligophenylenevinylene bridges could be useful for
      wiring molecular electronic elements.

PMID- 11222853
TI  - Automated solid-phase synthesis of oligosaccharides.
AB  - Traditionally, access to structurally defined complex carbohydrates has been very
      laborious. Although recent advancements in solid-phase synthesis have made the
      construction of complex oligosaccharides less tedious, a high level of technical
      expertise is still necessary to obtain the desired structures. We describe the
      automated chemical synthesis of several oligosaccharides on a solid-phase
      synthesizer. A branched dodecasaccharide was synthesized through the use of
      glycosyl phosphate building blocks and an octenediol functionalized resin. The
      target oligosaccharide was readily obtained after cleavage from the solid
      support. Access to certain complex oligosaccharides now has become feasible in a
      fashion much like the construction of oligopeptides and oligonucleotides.

PMID- 11222854
TI  - Redox state of Mars' upper mantle and crust from Eu anomalies in shergottite
      pyroxenes.
AB  - The oxidation state of basaltic martian meteorites is determined from the
      partitioning of europium (Eu) in their pyroxenes. The estimated redox conditions
      for these samples correlate with their initial neodymium and strontium isotopic
      compositions. This is interpreted to imply varying degrees of interaction between
      the basaltic parent melts, derived from a source in the martian mantle, and a
      crustal component. Thus, the mantle source of these martian basalts may have a
      redox state close to that of the iron-wustite buffer, whereas the martian crust
      may be more oxidized (with a redox state higher than or equal to that of the
      quartz-fayalite-magnetite buffer). A difference in redox state of more than 3 log
      units between mantle and crustal reservoirs on Mars could result from oxidation
      of the crust by a process such as aqueous alteration, together with a subsequent
      lack of recycling of this oxidized crust through the reduced upper mantle.

PMID- 11222855
TI  - Impact event at the Permian-Triassic boundary: evidence from extraterrestrial
      noble gases in fullerenes.
AB  - The Permian-Triassic boundary (PTB) event, which occurred about 251.4 million
      years ago, is marked by the most severe mass extinction in the geologic record.
      Recent studies of some PTB sites indicate that the extinctions occurred very
      abruptly, consistent with a catastrophic, possibly extraterrestrial, cause.
      Fullerenes (C60 to C200) from sediments at the PTB contain trapped helium and
      argon with isotope ratios similar to the planetary component of carbonaceous
      chondrites. These data imply that an impact event (asteroidal or cometary)
      accompanied the extinction, as was the case for the Cretaceous-Tertiary
      extinction event about 65 million years ago.

PMID- 11222856
TI  - Costs and the diversification of exaggerated animal structures.
AB  - Sexual selection can favor production of extravagant ornaments and weapons in the
      contest for access to the opposite sex. Existing explanations for the diversity
      of sexually selected structures focus on reproductive benefits conferred by
      particular ornament or weapon morphologies. Here, I show that costs of weapon
      production also may drive patterns of weapon evolution. In beetles, production of
      horns reduces the size of neighboring morphological structures (antennae, eyes,
      or wings, depending on the location of the horns), and these tradeoffs reveal
      unexpected functional associations between ecology and horn morphology. This
      study illustrates a critical but overlooked role of costs in sexual selection and
      has implications for understanding the evolution of animal morphology.

PMID- 11222857
TI  - TCR-induced transmembrane signaling by peptide/MHC class II via associated Ig
      alpha/beta dimers.
AB  - Previous findings suggest that during cognate T cell-B cell interactions, major
      histocompatability complex (MHC) class II molecules transduce signals, leading to
      Src-family kinase activation, Ca2+ mobilization, and proliferation. Here, we show
      that antigen stimulation of resting B cells induces MHC class II molecules to
      associate with Immunoglobulin (Ig)-alpha/Ig-beta (CD79a/CD79b) heterodimers,
      which function as signal transducers upon MHC class II aggregation by the T cell
      receptor (TCR). The B cell receptor (BCR) and MHC class II/Ig-alpha/Ig-beta are
      distinct complexes, yet class II-associated Ig-alpha/beta appears to be derived
      from BCR. Hence, Ig-alpha/beta are used in a sequential fashion for transduction
      of antigen and cognate T cell help signals.

PMID- 11222858
TI  - Contribution of receptor editing to the antibody repertoire.
AB  - Receptor editing, clonal deletion, and anergy are the mechanisms by which B cells
      maintain tolerance to self antigens. To determine the extent to which receptor
      editing shapes the normal antibody repertoire, we generated an immunoglobulin
      kappa polymorphism that facilitates the detection of editing of immunoglobulin
      light chains in vivo. We found that B cells are targeted for editing during a 2
      hour delay in development at the pre-BII cell stage, and that about 25% of all
      antibody molecules are produced by gene replacement. These results suggest that
      receptor editing represents a major force in shaping the antibody repertoire.

PMID- 11222859
TI  - Induction of direct antimicrobial activity through mammalian toll-like receptors.
AB  - The mammalian innate immune system retains from Drosophila a family of homologous
      Toll-like receptors (TLRs) that mediate responses to microbial ligands. Here, we
      show that TLR2 activation leads to killing of intracellular Mycobacterium
      tuberculosis in both mouse and human macrophages, through distinct mechanisms. In
      mouse macrophages, bacterial lipoprotein activation of TLR2 leads to a nitric
      oxide-dependent killing of intracellular tubercle bacilli, but in human monocytes
      and alveolar macrophages, this pathway was nitric oxide-independent. Thus,
      mammalian TLRs respond (as Drosophila Toll receptors do) to microbial ligands and
      also have the ability to activate antimicrobial effector pathways at the site of
      infection.

PMID- 11222860
TI  - Requirement of a centrosomal activity for cell cycle progression through G1 into
      S phase.
AB  - Centrosomes were microsurgically removed from BSC-1 African green monkey kidney
      cells before the completion of S phase. Karyoplasts (acentrosomal cells) entered
      and completed mitosis. However, postmitotic karyoplasts arrested before S phase,
      whereas adjacent control cells divided repeatedly. Postmitotic karyoplasts
      assembled a microtubule-organizing center containing gamma-tubulin and
      pericentrin, but did not regenerate centrioles. These observations reveal the
      existence of an activity associated with core centrosomal structures-distinct
      from elements of the microtubule-organizing center-that is required for the
      somatic cell cycle to progress through G1 into S phase. Once the cell is in S
      phase, these core structures are not needed for the G2-M phase transition.

PMID- 11222861
TI  - Centrosome-dependent exit of cytokinesis in animal cells.
AB  - As an organelle coupling nuclear and cytoplasmic divisions, the centrosome is
      essential to mitotic fidelity, and its inheritance could be critical to
      understanding cell transformation. Investigating the behavior of the centrosome
      in living mitotic cells, we documented a transient and remarkable postanaphase
      repositioning of this organelle, which apparently controls the release of central
      microtubules from the midbody and the completion of cell division. We also
      observed that the absence of the centrosome leads to defects in cytokinesis.
      Together with recent results in yeasts, our data point to a conserved centrosome
      dependent pathway that integrates spatial controls into the decision of
      completing cell division, which requires the repositioning of the centrosome
      organelle.

PMID- 11222862
TI  - Structure of a Bag/Hsc70 complex: convergent functional evolution of Hsp70
      nucleotide exchange factors.
AB  - Bag (Bcl2-associated athanogene) domains occur in a class of cofactors of the
      eukaryotic chaperone 70-kilodalton heat shock protein (Hsp70) family. Binding of
      the Bag domain to the Hsp70 adenosine triphosphatase (ATPase) domain promotes
      adenosine 5'-triphosphate-dependent release of substrate from Hsp70 in vitro. In
      a 1.9 angstrom crystal structure of a complex with the ATPase of the 70
      kilodalton heat shock cognate protein (Hsc70), the Bag domain forms a three-helix
      bundle, inducing a conformational switch in the ATPase that is incompatible with
      nucleotide binding. The same switch is observed in the bacterial Hsp70 homolog
      DnaK upon binding of the structurally unrelated nucleotide exchange factor GrpE.
      Thus, functional convergence has allowed proteins with different architectures to
      trigger a conserved conformational shift in Hsp70 that leads to nucleotide
      exchange.

PMID- 11222864
TI  - Modulation of oscillatory neuronal synchronization by selective visual attention.
AB  - In crowded visual scenes, attention is needed to select relevant stimuli. To
      study the underlying mechanisms, we recorded neurons in cortical area V4 while
      macaque monkeys attended to behaviorally relevant stimuli and ignored
      distracters. Neurons activated by the attended stimulus showed increased gamma
      frequency (35 to 90 hertz) synchronization but reduced low-frequency (<17 hertz)
      synchronization compared with neurons at nearby V4 sites activated by
      distracters. Because postsynaptic integration times are short, these localized
      changes in synchronization may serve to amplify behaviorally relevant signals in
      the cortex.

PMID- 11222865
TI  - Organophosphate antagonism of the androgen receptor.

PMID- 11222863
TI  - Taste receptor cells that discriminate between bitter stimuli.
AB  - Recent studies showing that single taste bud cells express multiple bitter taste
      receptors have reignited a long-standing controversy over whether single
      gustatory receptor cells respond selectively or broadly to tastants. We examined
      calcium responses of rat taste receptor cells in situ to a panel of bitter
      compounds to determine whether individual cells distinguish between bitter
      stimuli. Most bitter-responsive taste cells were activated by only one out of
      five compounds tested. In taste cells that responded to multiple stimuli, there
      were no significant associations between any two stimuli. Bitter sensation does
      not appear to occur through the activation of a homogeneous population of broadly
      tuned bitter-sensitive taste cells. Instead, different bitter stimuli may
      activate different subpopulations of bitter-sensitive taste cells.

PMID- 11222866
TI  - Toxicologists and the founding of the society of toxicology.

PMID- 11222867
TI  - Challenges and limitations of gene expression profiling in mechanistic and
      predictive toxicology.
AB  - RNA and protein expression profiling technologies have revolutionized how
      toxicologists can study the molecular basis of adverse effects of chemicals and
      drugs. It is expected that these new technologies will afford efficient and high
      throughput means to delineate mechanisms of action and predict toxicity of
      unknown agents. To reach these goals, a more thorough understanding of the
      constraints of the methodology is needed to design genome-scale studies and to
      interpret the vast amount of data collected. This paper addresses some of the
      limitations and uncertainties of gene expression profiling in mechanistic and
      predictive toxicology with respect to the expectations of toxicogenomics. The
      challenges associated with interpreting information from large-scale gene
      expression experiments in vivo is also discussed.

PMID- 11222868
TI  - Cytochrome p450-dependent metabolism of trichloroethylene in rat kidney.
AB  - The metabolism of trichloroethylene (Tri) by cytochrome P450 (P450) was studied
      in microsomes from liver and kidney homogenates and from isolated renal proximal
      tubular (PT) and distal tubular (DT) cells from male Fischer 344 rats. Chloral
      hydrate (CH) was the only metabolite consistently detected and was used as a
      measurement of P450-dependent metabolism of Tri. Pretreatment of rats with
      pyridine increased CH formation in both liver and kidney microsomes, whereas
      pretreatment of rats with clofibrate increased CH formation only in kidney
      microsomes. Pyridine increased CYP2E1 expression in both liver and kidney
      microsomes, whereas clofibrate had no effect on hepatic but increased renal
      CYP2E1 and CYP2C11 protein levels. These results suggest a role for CYP2E1 in
      both the hepatic and renal metabolism of Tri and a role for CYP2C11 in the renal
      metabolism of Tri. Studies with the general P450 inhibitor SKF-525A and the
      CYP2E1 competitive substrate chlorzoxazone provided additional support for the
      role of CYP2E1 in both tissues. CH formation was higher in PT cells than in DT
      cells and was time and reduced nicotinamide adenine dinucleotide phosphate
      (NADPH) dependent. However, pretreatment of rats with either pyridine or
      clofibrate had no effect on CYP2E1 or CYP2C11 protein levels or on CH formation
      in isolated cells. These data show for the first time that Tri can be metabolized
      to at least one of its P450 metabolites in the kidneys and quantitate the effect
      of P450 induction on Tri metabolism in the rat kidney.

PMID- 11222869
TI  - PBPK modeling of canine inhalation exposures to halogenated hydrocarbons.
AB  - Human exposure guidelines for halogenated hydrocarbons (halons) and halon
      replacement chemicals have been established using dose-response data obtained
      from canine cardiac sensitization studies. In order to provide a tool for
      decision makers and regulators tasked with setting guidelines for egress from
      exposure to halon replacement chemicals, a quantitative approach, using a
      physiologically based pharmacokinetic model, was established that allowed
      exposures to be assessed in terms of the chemical concentrations in blood during
      the exposure. This model, which includes a respiratory tract compartment
      containing a dead-space region, a pulmonary exchange area, and a breath-by-breath
      description of respiratory tract uptake, allows successful simulation of exhaled
      breath concentrations of humans during the first minute of exposure to the
      anesthetics halothane, isoflurane, and desflurane. In the current study, the
      human model was modified with canine parameters and validated with data obtained
      from dog studies with halothane, isoflurane, desflurane, and CFC-11. With
      consideration of appropriate values for ventilation and cardiac output, the model
      successfully simulated data collected under a variety of exposure scenarios. The
      canine model can be used for simulating blood concentrations associated with the
      potential for cardiac sensitization. These target blood concentrations can then
      be used with the human model for establishing safe human exposure duration.
      Development of the canine model stresses the need for appropriate data collection
      for model validation.

PMID- 11222870
TI  - Toxicology and carcinogenesis studies of p,p'-dichlorodiphenyl sulfone in rats
      and mice.
AB  - p,p'-Dichlorodiphenyl sulfone (DDS) is used as a starting material in the
      production of polysulfones and polyethersufones, a family of thermoplastics. DDS
      was studied because of its high production volume and use. In toxicology studies,
      10 Fischer 344 rats and 10 B6C3F1 mice/sex/group were fed diets containing 0, 30,
      100, 300, 1,000 or 3,000 ppm DDS for 14 weeks. All animals survived until the end
      of the studies. Mean body weights of groups exposed to 300 ppm or greater were
      significantly decreased. Liver and kidney in rats and liver in mice were the
      major target organs of DDS toxicity. Dose-related increases in liver weights and
      incidences of centrilobular hepatocyte hypertrophy were observed in DDS-exposed
      groups. Nephropathy was seen in male and female rats only at and above 300 ppm.
      Neurotoxicity evaluations were negative in DDS-treated animals. Clinical
      chemistry and hematology parameters were minimally affected. In the 2-year
      toxicity and carcinogenicity studies, 50 rats and 50 mice/sex/group were fed
      diets containing 0, 10 (male rats), 30, 100, or 300 ppm DDS for 104 to 105 weeks.
      Survival of exposed groups was not affected. There were no clinical signs of
      toxicity related to DDS exposure. Final mean body weights were 2-17% lower in DDS
      treated groups. Liver was the only target organ of DDS-induced toxicity. The
      incidence of centrilobular hepatocyte hypertrophy in mice and rats, and the
      incidence of bile duct hyperplasia and centrilobular degeneration in female rats
      was significantly greater than in controls. A no-observed-adverse-effect level
      (NOAEL) of 30 ppm DDS in the diet (1.5 mg/kg body weight) was established for
      rats. DDS was not carcinogenic in these studies.

PMID- 11222871
TI  - Increased ErbB-2 tyrosine kinase activity, MAPK phosphorylation, and cell
      proliferation in the prostate cancer cell line LNCaP following treatment by
      select pesticides.
AB  - The oncogene erbB-2 codes for a receptor tyrosine kinase that functions as a key
      mitotic signal in a variety of cell types. Amplification or overexpression of
      erbB-2 occurs in many forms of cancer, such as of the breast, colon, and
      prostate, and is an indicator of poor prognosis in those diseases. In the human
      prostate cancer cell lines LNCaP and PC-3, erbB-2 kinase was activated by
      pesticides of different chemical classes: (1) the organochlorine insecticides
      beta-hexa-chlorocyclohexane (beta-HCH), o,p'-dichlorodiphenyltrichloroethane
      (o,p'-DDT), and heptachlor epoxide; (2) the pyrethroid insecticide trans
      permethrin, and (3) the fungicide chlorothalonil. o,p'-DDT also causes
      phosphorylation of mitogen-activated protein kinase (MAPK) and cellular
      proliferation of the androgen-dependent LNCaP line. However, no proliferative
      effect was observed in the androgen-independent PC-3 line. The proliferative
      effect of o,p'-DDT in LNCaP could not be blocked by the androgen receptor
      antagonist p,p'-dichlorodiphenyldichloroethene (p,p'-DDE), indicating that this
      effect of o,p'-DDT does not occur through direct interaction with the androgen
      receptor. Together these data demonstrate a putative mechanism for the action of
      certain pesticides in hormonal carcinogenesis.

PMID- 11222872
TI  - Mechanisms of extrahepatic tumor induction by peroxisome proliferators in male CD
      rats.
AB  - Wyeth-14,643 (WY) and ammonium perfluorooctanoate (C8) belong to a diverse class
      of compounds which have been shown to produce hepatic peroxisome proliferation in
      rodents. From previous work, WY, but not C8, has been shown to produce
      hepatocellular carcinoma in rats, while C8 has been shown to produce Leydig cell
      adenomas. In addition, based on a review of bioassay data a relationship appears
      to exist between peroxisome-proliferating compounds and Leydig cell adenoma and
      pancreatic acinar cell hyperplasia/adenocarcinoma formation. To further
      investigate the relationship between peroxisome-proliferating compounds and
      hepatic, Leydig cell, and pancreatic acinar cell tumorigenesis, a 2-year feeding
      study in male CD rats was initiated to test the hypothesis that peroxisome
      proliferating compounds induce a tumor triad (liver, Leydig cell, pancreatic
      acinar cell), and to examine the potential mechanism for the Leydig cell tumors.
      The study was conducted using 50 ppm WY and 300 ppm C8. The concentration of WY
      in the diet was decreased to 25 ppm on test day 301 due to increased mortality.
      In addition to the ad libitum control, a second control was pair-fed to the C8
      group. Interim sacrifices were performed at 1- or 3-month intervals. Peroxisome
      proliferation measured by beta-oxidation activity and cell proliferation were
      measured in the liver and testis at all time points and in the pancreas beginning
      at the 9-month time point (cell proliferation only). Serum hormone concentrations
      (estradiol, testosterone, LH, FSH, and prolactin) were also measured at each time
      point. Increased relative liver weights and hepatic beta-oxidation activity were
      observed in both the WY- and C8-treated rats at all time points. In contrast,
      hepatic cell proliferation was significantly increased only in the WY-treated
      group. Neither WY nor C8 significantly altered the rate of Leydig cell beta
      oxidation or Leydig cell proliferation when compared to the control groups.
      Moreover, the basal rate of beta-oxidation in Leydig cells was approximately 20
      times less than the rate of hepatic beta-oxidation. There were no biologically
      meaningful differences in serum testosterone, FSH, prolactin, or LH
      concentrations in the WY- and C8-treated rats when compared to their respective
      controls. There were, however, significant increases in serum estradiol
      concentrations in the WY- and C8-treated rats at 1, 3, 6, 9, 15, 18, and 21
      months. At 12 months, only the C8-treated rats had elevated serum estradiol
      concentrations when compared to the pair-fed control. Histopathological
      evaluation revealed compound-related increases in liver, Leydig cell, and
      pancreatic acinar cell tumors in both WY- and C8-treated rats. The data support
      the hypothesis that the peroxisome-proliferating compounds induce the previously
      described tumor triad. In addition, both C8 and WY produced a sustained increase
      in serum estradiol concentrations that correlated with the potency of the 2
      compounds to induce Leydig cell tumors (i.e., WY caused a more consistent
      sustained increase in serum estradiol throughout the entire study, and more
      specifically at the end of the study, than did C8). This study suggests that
      estradiol may play a role in enhancement of Leydig cell tumors in the rat, and
      that peroxisome proliferators may induce tumors via a non-LH type mechanism.

PMID- 11222873
TI  - Androgen receptor antagonism by the organophosphate insecticide fenitrothion.
AB  - Organophosphate insecticides represent one of the most widely used classes of
      pesticides with high potential for human exposure in both rural and residential
      environments. We investigated the interaction of the organophosphothioate
      pesticide fenitrothion (O,O-dimethyl O-(4-nitro-m-tolyl) phosphorothioate) with
      the human androgen receptor (AR). Fenitrothion blocked dihydrotestosterone
      dependent AR activity in a concentration-dependent and competitive manner in
      HepG2 human hepatoma liver cells transiently transfected with human AR and an AR
      dependent luciferase reporter gene. Schild regression analysis yielded an
      equilibrium dissociation constant value of 2.18 x 10(-8) M. To determine the
      antiandrogenic potential of fenitrothion in vivo, 7-week-old castrated Sprague
      Dawley rats were dosed once a day for 7 days with testosterone propionate (50
      microg/day, sc) plus gavage doses of either corn oil vehicle or fenitrothion (15
      or 30 mg/kg/day). An additional group of rats was given testosterone propionate
      and flutamide (50 mg/kg/day). Motor activity and acetylcholinesterase activity in
      whole blood and brain were also assessed. Both fenitrothion and the reference
      antiandrogen flutamide caused significant decreases in the ventral prostate,
      seminal vesicle, and levator ani plus bulbocavernosus muscles tissue weights. In
      contrast, blood acetylcholinesterase activity, a standard biomarker of
      organophosphate poisoning, was only inhibited at the higher dose of fenitrothion
      (30 mg/kg). Our results demonstrate that fenitrothion is a competitive AR
      antagonist, comparable in potency to the pharmaceutical antiandrogen flutamide
      and more potent, based on in vitro assays, than the known environmental
      antiandrogens linuron and p,p'-, 2,2-bis(p-hydroxyphenyl)-1,1-dichloroethylene (
      p,p'-DDE).

PMID- 11222874
TI  - Evaluation of the male pubertal assay's ability to detect thyroid inhibitors and
      dopaminergic agents.
AB  - The male pubertal onset assay is under consideration as an alternate Tier I
      screening assay to detect potential endocrine active chemicals (EACs) acting
      through a variety of steroid hormone and thyroid hormone receptor-mediated and
      non-receptor-mediated mechanisms. This study focused on the assay's ability to
      detect several non-receptor-mediated EACs. Weanling male CD rats (21 days old)
      were dosed for 30 d by gavage with vehicle (0.5% METHOCEL) or the following EAC
      classes (mg/kg/d): a potent thyroid agent (6-propylthiouracil, PTU, 240), a weak
      thyroid agent (phenobarbital, PB, 50 or 100), a dopamine antagonist (haloperidol,
      HALO, 2 or 4), or a dopamine agonist (bromocryptine, BRC, 10 or 50). In vehicle
      treated males, preputial separation (PPS) occurred at 44.4 +/- 2.0 days of age.
      Age at PPS was delayed with PTU and 50 BRC, treatments that also delayed growth.
      Absolute testes and/or epididymal weights were decreased by PTU and 100 PB. BRC
      (50) and PB (100) decreased absolute prostate and seminal vesicle weights.
      Relative thyroid weights were altered by HALO, PTU, and PB, agents that
      significantly decreased serum T(4) levels. PTU increased serum thyroid
      stimulating hormone (TSH) by 8.5 times and markedly altered thyroid histology,
      whereas HALO and PB did not significantly increase TSH and had marginal effects
      on thyroid histology. Thus, this assay detected both strong (PTU) and weak (PB)
      thyroid agents as well as the dopamine agonist BRC; however, its ability to
      detect dopamine antagonists remains unproven. These results confirm that thyroid
      weight measurements, although not required in the current male pubertal assay
      protocol, may add valuable information for interpretation of thyroid effects. Due
      to the apical nature of the male pubertal assay end points, additional work will
      be required to establish definitive criteria for a positive result in this assay.

PMID- 11222875
TI  - Acquired resistance to Ah receptor agonists in a population of Atlantic killifish
      (Fundulus heteroclitus) inhabiting a marine superfund site: in vivo and in vitro
      studies on the inducibility of xenobiotic metabolizing enzymes.
AB  - New Bedford Harbor (NBH), MA, is a federal Superfund site that is heavily
      contaminated with polychlorinated biphenyls (PCBs) and other halogenated aromatic
      hydrocarbons (HAHs), including some potent aryl hydrocarbon receptor (AhR)
      agonists. A population of Atlantic killifish (Fundulus heteroclitus) continues to
      inhabit this site, despite accumulating extraordinarily high concentrations of
      PCBs (272 microg/g dry weight). To determine if NBH killifish have developed
      resistance to HAHs that act through the AhR, we examined the inducibility of
      cytochrome P4501A1 (CYP1A1), UDP glucuronosyl transferase (UGT), and glutathione
      S-transferase (GST) in fish from NBH and a reference site, Scorton Creek (SC,
      Cape Cod, MA; PCB concentrations 0.177 microg/g dry weight). 2,3,7,8
      Tetrachlorodibenzofuran (TCDF) induced CYP1A1 mRNA, protein, and activity in SC
      fish in all tissues examined (liver, heart, gut, gill, kidney, spleen, and
      gonad). In contrast, NBH fish expressed low levels of CYP1A1 and showed no
      induction of CYP1A1 mRNA, protein, or activity by TCDF, or induction that was
      lower in magnitude or required higher doses of inducer. p-Nitrophenol UGT
      activity was not induced by TCDF in either population, while GST activity with 1
      chloro-2,4-dinitrobenzene as substrate was induced only in NBH fish in one
      experiment. Inducibility of CYP1A1 by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      or beta-naphthoflavone (BNF) was measured in primary hepatocyte cultures prepared
      from SC and NBH fish. TCDD induced CYP1A1 activity (ethoxyresorufin O-deethylase)
      to the same degree in hepatocytes from both populations, demonstrating the
      functionality of the AhR signaling pathway in NBH fish. However, hepatocytes from
      NBH fish were 14-fold less sensitive to TCDD than were those from SC fish. The
      nonhalogenated AhR agonist BNF also induced CYP1A1 in cells from both
      populations, although with only a 3-fold difference in sensitivity (NBH < SC).
      These results indicate that chronic exposure to high levels of HAHs has led to a
      reduction in the sensitivity of NBH killifish to AhR agonists. The resistance is
      systemic and pretranslational, and exhibits compound-specific differences in
      magnitude. These findings suggest an alteration in the AhR signal transduction
      pathway in NBH fish.

PMID- 11222876
TI  - Production of DNA strand breaks in vitro and reactive oxygen species in vitro and
      in HL-60 cells by PCB metabolites.
AB  - PCBs are industrial chemicals that continue to contaminate our environment. They
      cause various toxic effects in animals and in exposed human populations. The
      mechanisms of toxicity, however, are not completely understood. PCBs are
      metabolized by cytochromes P450 to mono- and dihydroxylated compounds. Dihydroxy
      PCBs can potentially be oxidized to the corresponding quinones. We hypothesized
      that reactive oxygen species (ROS) are produced by redox reactions of PCB
      metabolites. We tested several synthetic dihydroxy- and quinoid-PCBs with 1-3
      chlorines for their potential to produce ROS in vitro and in HL-60 human leukemia
      cells, and DNA strand breaks in vitro. All dihydroxy-PCBs tested produced
      superoxide. The quinones generated superoxide only in the presence of GSH,
      probably during the autoxidation of the glutathione conjugates. We observed
      increased superoxide production with decreasing halogenation. Incubation of
      dihydroxy-PCBs or PCB quinones + GSH with plasmid DNA resulted in DNA strand
      break induction in the presence of Cu(II). Tests with various ROS scavengers
      indicated that hydroxyl radicals and singlet oxygen are likely involved in this
      strand break induction. Finally, dihydroxy- and quinoid PCBs also produced ROS in
      HL-60 cells in a dose- and time-dependent manner. We conclude that dihydroxylated
      PCBs, and PCB quinones after reaction with GSH, produce superoxide and other ROS
      both in vitro and in HL-60 cells, and oxidative DNA damage in the form of DNA
      strand breaks in vitro. The reactions seen in vitro and in cells may well be a
      predictor of the toxicity of PCBs in animals.

PMID- 11222877
TI  - Seizure activity and hyperthermia potentiate the increases in dopamine and
      serotonin extracellular levels in the amygdala during exposure to d-amphetamine.
AB  - Behavioral stereotypy, hyperthermia, and convulsive activity produced by exposure
      to multiple doses of d-amphetamine (AMPH) were related to changes in the
      extracellular levels of dopamine and serotonin (5-HT) in the amygdala, using the
      technique of microdialysis in awake and freely moving rats. Hyperactivity and
      stereotypy, as well as increases in microdialysis dopamine levels ranging from
      100-300% of pre-AMPH basal microdialysate levels (BL), occurred during exposure
      to 3 doses of 2.5 mg/kg (3 x 2.5 mg/kg) AMPH. Three doses of 5 mg/kg produced a
      more intense stereotypic behavior as well as hyperthermia, and resulted in large
      increases in the peak dopamine levels (700% BL) while 5-HT levels were increased
      to a lesser extent (300% BL). The highest doses tested of 3 x 15 mg/kg produced
      convulsive activity, seizures, intense stereotypy and hyperthermia with peak
      microdialysate dopamine (1300% BL) and 5-HT levels (1800% BL) that were 2-fold
      and 6-fold greater, respectively, than those at the 3 x 5-mg/kg doses.
      Microdialysate glutamate levels were not changed by AMPH exposure. Rats that did
      not become hyperthermic when dosed with 15 mg/kg AMPH in a cold environment (10
      degrees C) exhibited some hyperactivity and stereotypic behavior, but not overt
      convulsive behavior. Dopamine and 5-HT levels in these rats were significantly
      reduced by about 75% and 60%, respectively, compared to the room-temperature
      group. Inclusion of 2 microM tetrodotoxin (TTX) in the microdialysis buffer
      significantly reduced the 15-mg/kg AMPH-induced increases in dopamine by 30% and
      the increase in 5-HT levels by 70% at room temperature. These results indicate
      that a smaller portion of the dopamine release evoked by doses of AMPH that
      induce seizure activity is neuronal impulse-dependent while the majority of 5-HT
      released is impulse-dependent. Irrespective of impulse activity, the hyperthermia
      alone markedly potentiated dopamine release but had a lesser effect on 5-HT
      release. Thus, there are differences in the regulation of dopamine and serotonin
      release in the amygdala from high doses of AMPH, which are known to produce
      neurotoxicity. Further studies are necessary to determine the impact of these
      differences in release on AMPH neurotoxicity.

PMID- 11222878
TI  - Evaluation of the developmental toxicity of isoeugenol in Sprague-Dawley (CD)
      rats.
AB  - Isoeugenol, used as a perfumery and flavoring agent, was evaluated for
      developmental toxicity. Timed-pregnant CD((R)) outbred albino Sprague-Dawley rats
      received isoeugenol (250, 500, or 1000 mg/kg/day) or vehicle (5 ml/kg corn oil)
      by gavage on gestational days (gd) 6 through 19. Maternal food and water
      consumption, body weight, and clinical signs were monitored at regular intervals
      throughout gestation. At termination (gd 20), confirmed-pregnant females (23-25
      per group) were evaluated for gestational outcome. All live fetuses were weighed
      and examined for external malformations, and approximately 50% were evaluated for
      visceral or skeletal malformations. There were no treatment-related maternal
      deaths. Clinical signs associated with isoeugenol exposure included dose-related
      evidence of sedation and aversion to treatment (rooting behavior) in all
      isoeugenol groups, as well as an increased incidence of piloerection at >/= 500
      mg/kg/day. Maternal body weight, weight gain, and gestational weight gain
      (corrected for gravid uterine weight) were reduced at all doses in a dose-related
      manner. Gravid uterine weight was significantly decreased at the mid and high
      doses, whereas maternal relative liver weight was increased at all three dose
      levels. During treatment (gd 6 to 20), maternal relative food consumption was
      significantly decreased at the high dose, and maternal relative water consumption
      was elevated in the mid- and high-dose groups. Prenatal mortality (resorption or
      late fetal death) was unaffected. At 1000 mg/kg/day, average fetal body
      weight/litter was decreased by 7% (male) or 9% (female). Incidences of fetal
      morphological anomalies were statistically equivalent among groups, except for an
      increase in the incidence of unossified sternebra(e), a skeletal variation, at
      the high dose. In summary, the maternal toxicity lowest observed adverse effect
      level (LOAEL) was 250 mg/kg/day based primarily on reduced body weight and
      gestational weight gain (corrected for gravid uterine weight), and the maternal
      toxicity no observed adverse effect level (NOAEL) was not determined in this
      study. The developmental toxicity LOAEL was 1000 mg/kg/day based on intrauterine
      growth retardation and mildly delayed skeletal ossification. The developmental
      toxicity NOAEL was 500 mg/kg/day.

PMID- 11222879
TI  - Developmental toxicity studies in rats and rabbits on 2,4-dichlorophenoxyacetic
      acid and its forms.
AB  - The potential for 2,4-D and its salts and esters to induce developmental toxicity
      was investigated in rats (8 studies) and rabbits (7 studies). Maternal toxicity
      associated with exposure was dependent on the dose level expressed as 2,4-D acid
      equivalents. The severity of the maternal effect was correlated to the 2,4-D acid
      equivalent dose, with increasing dose levels that exceeded renal clearance
      causing increasingly more severe maternal effects. In both species, maternal body
      weight effects began to be manifested at dose levels of 30 mg 2,4-D acid
      equivalent/kg/day. At higher dose levels (50-75 mg/kg/day in rats and 75-90
      mg/kg/day in rabbits), body weights and feed consumption were more severely
      affected. At dose levels > or =90 mg/kg/day in rats, clinical signs of toxicity
      (ataxia, muscular stiffness, and decreased motor activity) and mortality were
      noted. The no-observed-adverse-effect level (NOAEL) for maternal toxicity in both
      species across the family of 2,4-D salts and esters was approximately 10
      mg/kg/day. Significantly decreased fetal body weights and increased fetal
      variations were seen in rats only at maternally toxic dose levels in excess of 90
      mg/kg/day acid equivalent. At maternally toxic doses in rabbits, embryonal and
      fetal development were essentially unaffected. There were no effect on maternal
      reproductive measures such as litter size, resorption rates, or fetal body
      weights, and there was no evidence of teratogenic activity. In summary,
      equivalent toxicity of the salts and esters is consistent with rapid and complete
      metabolic conversion to 2,4-D acid. No adverse fetal effects were noted at dose
      levels that did not also produce evidence of maternal toxicity or exceed renal
      clearance of 2,4-D indicating that the developing rat and rabbit fetus were not
      uniquely sensitive to 2,4-D and its forms.

PMID- 11222880
TI  - Maternal exposure to a low dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      suppressed the development of reproductive organs of male rats: dose-dependent
      increase of mRNA levels of 5alpha-reductase type 2 in contrast to decrease of
      androgen receptor in the pubertal ventral prostate.
AB  - To assess the health risks associated with exposure to 2,3,7,8-tetrachlorodebenzo
      p-dioxin (TCDD), we studied the effects of a relatively low dose of TCDD on the
      male reproductive system of rats, using the experimental protocol of T. A. Mably
      et al. (1992, Toxicol. Appl. Pharmacol. 114, 97-107, 108-117, 118-126), and
      searched for the most sensitive and reliable among several indices of TCDD
      toxicity. Pregnant Holtzman rats were given a single oral dose of 0, 12.5, 50,
      200, or 800 ng TCDD/kg body weight on gestational day (GD) 15, and male offspring
      were sacrificed on postnatal day (PND) 49 or 120. GC-MS analysis of the abdominal
      fat tissue and testis clearly showed increased amounts of TCDD in these
      offspring. However, there was no TCDD effect on body weight of offspring. There
      were no changes on testicular or epididymal weights by TCDD administration, even
      at the 800-ng/kg dose in rats sacrificed on either PND 49 or 120. In addition,
      TCDD administration resulted in no changes in daily sperm production or sperm
      reserve at any of the doses used. However, the weight of the urogenital complex,
      including the ventral prostate, was significantly reduced at doses of 200 and 800
      ng TCDD/kg in rats sacrificed on PND 120. Moreover, the anogenital distance (AGD)
      of male rats sacrificed on PND 120 showed a significant decrease in the groups
      receiving doses greater than 50 ng TCDD/kg. TCDD administration resulted in no
      apparent dose-dependent changes in levels of either serum testosterone or
      luteinizing hormone. Interestingly, reverse transcription-polymerase chain
      reaction (RT-PCR) analysis revealed that, in the ventral prostates of the PND 49
      group, TCDD administration resulted in both a dose-dependent increase in 5alpha
      reductase type 2 (5alphaR-II) mRNA level and a dose-dependent decrease in
      androgen receptor (AR) mRNA level. These results suggest that low-dose TCDD
      administration had a greater effect on the development of the external genital
      organs and ventral prostate than on development of the testis and other internal
      genital organs. Moreover, it is highly suggested that the decrease in the size of
      the ventral prostate by maternal TCDD exposure might be due to decreased
      responsiveness of the prostate to androgen due to an insufficient expression
      level of androgen receptor during puberty.

PMID- 11222881
TI  - Development of pulmonary tolerance in mice exposed to zinc oxide fumes.
AB  - As a result of repeated exposures to inhaled toxicants such as zinc oxide (ZnO),
      numerous individuals acquire tolerance to the exposures and display reduced
      symptoms. To ascertain whether tolerance is developed in an animal model, NIH
      Swiss mice were exposed to 1.0 mg/m(3) ZnO for 1, 3, or 5 days (1X, 3X, or 5X),
      and polymorphonuclear leukocyte (PMN) and protein levels in bronchoalveolar
      lavage (BAL) were measured. Mice acquired tolerance to neutrophil infiltration
      into the lungs, as total PMNs returned near baseline in 5X-exposed animals as
      compared to that of the 1X exposure group (1X = 2.7 +/- 0.4 x 10(4), 5X = 0.2 +/-
      0.1 x 10(4), mean +/- SE, p < 0.05). Development of tolerance to changes in
      lavageable protein, however, was not observed (1X = 313 +/- 29 microg/ml, 5X =
      684 +/- 71 microg/ml, p < 0.05). Tolerance to PMN influx did not persist
      following re-exposure to ZnO after 5 days of rest. In contrast to ZnO exposure,
      following single and repeated exposure to aerosolized endotoxin there was
      development of tolerance to protein in BAL (1X = 174 +/- 71 microg/ml, 5X = 166
      +/- 14 microg/ml, p > 0.05), but not to PMN influx (1X = 5.5 +/- 1.7 x 10(4),
      13.9 +/- 1.7 x 10(4), p < 0.05). Induction of lung metallothionein (MT) was also
      observed in mice exposed once or repeatedly exposed to ZnO, suggesting that MT
      may play a role in its molecular mechanism.

PMID- 11222882
TI  - Prior exposure to aged and diluted sidestream cigarette smoke impairs bronchiolar
      injury and repair.
AB  - The bronchiolar injury/repair response to naphthalene (NA) in mice includes acute
      distal airway epithelial injury that is followed by epithelial proliferation and
      redifferentiation, which result in repair of the epithelium within 14 days. To
      test whether prior exposure to aged and diluted sidestream cigarette smoke (TS)
      would alter the injury/repair response of the airway epithelium, adult mice were
      exposed to either filtered air (FA) or smoke for 5 days before injection with
      either corn oil carrier (CO) or naphthalene. Mice were killed 1 and 14 days after
      naphthalene injury. Lung and lobar bronchus were examined and measured using high
      resolution epoxyresin sections. The control group (FACOFA) that was exposed to
      filtered air/corn oil/filtered air contained airway epithelium similar to
      untreated controls at all airway levels. The group exposed to tobacco smoke/corn
      oil/filtered air (TSCOFA) contained some rounded cells in the small airways and
      some expansion of the lateral intercellular space in the larger airways. Necrotic
      or vacuolated cells were not observed. As expected, the epithelium in the group
      exposed to filtered air/naphthalene/filtered air (FANAFA) contained many light
      staining vacuolated Clara cells and squamated ciliated cells within distal
      bronchioles during the acute injury phase. Repair (including redifferentiation of
      epithelial cells and restoration of epithelial thickness) was nearly complete 14
      days after injury. The extent of Clara cell injury, as assessed in lobar bronchi,
      was not different between the four groups. Although the FANAFA group contained
      greater initial injury in the distal airways at 1 day, the group exposed to
      tobacco smoke/naphthalene/filtered air (TSNAFA) had the least amount of
      epithelial repair at 14 days after naphthalene treatment; many terminal
      bronchioles contained abundant squamated undifferentiated epithelium. We conclude
      that tobacco smoke exposure prior to injury (1) does not change the target site
      or target cell type of naphthalene injury, since Clara cells in terminal
      bronchioles are still selectively injured; (2) results in slightly diminished
      acute injury from naphthalene in distal bronchioles; and (3) delays bronchiolar
      epithelial repair.

PMID- 11222883
TI  - Acute canine model for drug-induced Torsades de Pointes in drug safety evaluation
      influences of anesthesia and validation with quinidine and astemizole.
AB  - An acute in vivo model for drug-induced torsades de pointes (TdP) for use in
      safety evaluation of drugs was developed using dogs with acute complete
      atrioventricular (AV) block. In order to study the effects of anesthetic agents
      on the inducibility of TdP, arrhythmias were induced by programmed electrical
      stimulation (PES) before and after cumulative intravenous administration of
      quinidine under anesthesia with sodium pentobarbital, halothane, or isoflurane.
      Both prolongation of the QTc and the incidence of TdP were greatest in dogs
      anesthetized with halothane and were smallest in those given pentobarbital,
      suggesting that halothane is the most suitable anesthetic for this TdP model. To
      further validate this model, astemizole was administered intravenously to other
      dogs under halothane anesthesia. Astemizole at 0.3 mg/kg caused slight
      prolongation of the QT interval but did not induce any arrhythmias. At 1 mg/kg,
      however, TdP were induced in 5 of 10 animals and in an additional 2 animals at 3
      mg/kg. Single and multiple ectopic beats preceded the induction of TdP, and the
      ectopic beats were observed in a dose-dependent manner. The plasma concentrations
      of quinidine in dogs with TdP were equivalent to or less than quinidine levels in
      humans with TdP, while those of astemizole were higher in dogs. In conclusion,
      this acute canine model of TdP with halothane anesthesia, complete AV block, PES,
      and simultaneous measurements of plasma drug concentration would be valuable for
      assessing the risk of drugs, especially I(Kr) blockers, to induce TdP in humans.

PMID- 11222884
TI  - Single-dose toxicity study of hepatic intra-arterial infusion of doxorubicin
      coupled to a novel magnetically targeted drug carrier.
AB  - The toxicity of a single hepatic intra-arterial administration of doxorubicin
      (DOX) coupled to a magnetically targeted drug carrier (MTC) was evaluated in a
      swine model. MTC is a microparticle composite of elemental iron and activated
      carbon. MTC-DOX is a new formulation of doxorubicin absorbed to the MTC and is
      designed for site-specific delivery to a solid tumor in the presence of an
      externally applied magnetic field. The magnetic field induces extravasation of
      MTCs through the vascular wall, leading to localization and retention in the
      tissue at the targeted site. Eighteen swine were assigned to 6 treatment groups,
      including 3 control groups (vehicle control, doxorubicin, MTC), and 3
      experimental groups that received the MTC-DOX preparation. Animals were given a
      single administration of test article, evaluated over 28 days, and then
      sacrificed. Signs of toxicity were monitored via clinical status, total body
      weight, gross and microscopic pathology, and serum chemistries. Angiography was
      used to determine the extent of any embolization present. There were no adverse
      effects observed in the DOX-alone group. Biologically significant, treatment
      related gross and microscopic lesions were limited to the targeted area of the
      liver only in groups receiving > or =75 mg of MTC (with or without doxorubicin).
      The severity of liver necrosis correlated to the severity of embolization
      following treatment. Doxorubicin was not freely circulating in any of the MTC-DOX
      groups, suggesting successful localization to the targeted site. The no-adverse
      effect level (NOAEL) was determined to be the MTC-DOX low-dose group.

PMID- 11222885
TI  - Increased metallothionein in mouse liver, kidneys, and duodenum during lactation.
AB  - Lactation-induced increases in cadmium absorption and retention have been
      demonstrated in mid-lactating mice, but no systematic measurements of endogenous
      metal-binding protein concentrations during lactation have been reported. Using
      Cd/hemoglobin radioassay, this study detected significant increases in
      metallothionein (MT) concentrations in liver (4-fold), kidneys (2-fold), and
      duodenum (2-fold), but not jejunum, of mouse dams on days 13 and 20 of lactation.
      These increases occurred in the absence of cadmium exposure and were specific to
      the lactation period; dams 5 days after weaning showed MT levels that were
      similar to those of nonpregnant (NP) mice. Similarly, Northern blot analyses of
      livers from lactating mice demonstrated that MT mRNA concentrations in maternal
      liver during mid-lactation were 6-fold higher than those observed 5 days after
      pups were weaned. Gel filtration of final supernatants from the Cd/hemoglobin
      assay confirmed that the Cd-binding molecule induced during lactation was indeed
      metallothionein. In addition, chromatographic analyses of cytosols from tissues
      taken from dams administered small amounts of Cd (66 ng/mouse) showed that the
      trace amounts of Cd absorbed through the maternal gastrointestinal tract during
      mid-lactation were also bound to the MT. These results indicate MT induction in
      mouse dams occurs as a physiological consequence of lactation, requiring no
      external stimulus. This induced MT participates in binding low levels of dietary
      cadmium consumed by the dam. During lactation, elevated maternal MT may affect
      pathways for essential trace metals as well as sequester toxic metals harmful to
      the neonate. Multiparous humans may have increased risk of accumulating
      environmental Cd.

PMID- 11222886
TI  - Early failure of a roughened surface, precoated femoral component in total hip
      arthroplasty.
AB  - A retrospective study was performed of a consecutive series examining 98 primary
      hip arthroplasties between March 1992 and December 1995. A second-generation
      roughened surface (grit-blasted), polymethyl methacrylate-precoated femoral
      component (Centralign prosthesis, Zimmer, Inc, Warsaw, IN) was used for all
      cases. Clinical and radiographic data were available for 84 hips (76 patients).
      The average duration of follow-up was 35.8 months. There were 10 failures by
      aseptic mechanical loosening of the femoral component (12%) at an average 30.6
      months postoperatively, 9 having been revised (11%). Revision was pending in the
      remaining patient. The average age of patients at primary arthroplasty for the
      failed group was 48.2 years compared with 63.4 years for the asymptomatic
      patients (P =.0008). In all cases, failures occurred by debonding of the femoral
      prosthesis from the cement mantle. We are not aware of any series using modern
      implant components and cementing techniques with an early mechanical failure rate
      of this magnitude.

PMID- 11222887
TI  - A novel method of cross-linking ultra-high-molecular-weight polyethylene to
      improve wear, reduce oxidation, and retain mechanical properties. Recipient of
      the 1999 HAP Paul Award.
AB  - Increasing cross-linking has been shown in vitro and in vivo to improve markedly
      the wear resistance of ultra-high-molecular-weight polyethylene (UHMWPE). The
      reduction in the mechanical properties of polyethylene under certain methods used
      to produce cross-linking has been a concern, however. These reductions are known
      to result from the processes used to increase the cross-link density and could
      affect the device performance in vivo. We present a novel method of increasing
      the cross-link density of UHMWPE in which UHMWPE is irradiated in air at an
      elevated temperature with a high-dose-rate electron beam and subsequently is melt
      annealed. This treatment improves markedly the wear resistance of the polymer as
      tested in a hip simulator, while maintaining the mechanical properties of the
      material within national and international standards. This method leads to the
      absence of detectable free radicals in the polymer and, as a result, excellent
      resistance to oxidation of the polymer.

PMID- 11222888
TI  - Survival analysis of cemented Press-Fit Condylar total knee arthroplasty.
AB  - We performed a survival analysis on 354 cemented primary Press-Fit Condylar (PFC)
      total knee arthroplasties (TKA) in 277 patients with prospective follow-up (mean,
      6 years; range, 2-11.7 years). No patient was lost to follow-up. Using revision
      for all causes as the endpoint, the cumulative survival rate at 10 years was
      95.5% (95% confidence interval, 90.1%-98.1%). The 10-year clinical outcome
      available on 41 patients was good, with significant improvement in pain and
      mobility assessments using the Nottingham data collection system. Our results
      indicate that the cemented PFC TKA has good long-term survival based on revision
      as the endpoint. Revision for implant failure is rare and brings to question
      modifications to this prosthesis.

PMID- 11222889
TI  - Patellar infera after high tibial osteotomy.
AB  - Forty-six knees in 41 patients that had undergone high tibial osteotomy (HTO)
      were evaluated to assess the potential correlation between alteration in the
      inclination of the proximal tibial articular surface and subsequent patellar
      height. Of the knees examined, 61% lost > or =5 degrees of posterior tibial
      inclination after HTO, whereas 54% of knees showed a relative lowering of
      patellar height of >10%, as measured by the Insall-Salvati ratio. The loss of the
      normal posterior tibial inclination was found to have a statistically significant
      association with the subsequent loss of the patellar height. Clinically, these
      results suggest that careful preservation of the posterior tibial inclination at
      the time of HTO could minimize the risk of subsequent patellar infera and
      alteration in patellofemoral mechanics.

PMID- 11222890
TI  - Does metal backing improve fixation of tibial component in unicondylar knee
      arthroplasty? A randomized radiostereometric analysis.
AB  - In a prospective, randomized study, patients with medial gonarthrosis stage I to
      III according to Ahlback were allocated to a unicondylar knee arthroplasty
      (Miller-Galante, Zimmer, Inc., Warsaw, IN) with an all-polyethylene tibial
      component or metal-backed tibial component of the same design. The purpose of the
      study was to evaluate if metal backing enhanced tibial component fixation. A
      total of 45 knees (42 patients; 23 metal-backed components and 22 all
      polyethylene components) were examined. We used radiostereometric analysis to
      measure micromotion of the tibial component over a period of 2 years after
      surgery. Hospital for Special Surgery score was used for clinical evaluation. We
      found no statistically significant differences in clinical results or migration
      of the tibial component over a 2-year follow-up period. These findings do not
      support better fixation of metal-backed tibial components. Because of these
      findings, we advocate all-polyethylene tibial components in unicondylar knee
      arthroplasties because of optimal biomechanical strength at a given height of
      tibial component, avoiding potential problems of modularity and minimizing the
      amount of interfaces, at a lower cost.

PMID- 11222891
TI  - Radiographic assessment of uncemented humeral components in total shoulder
      arthroplasty.
AB  - Seventy-two total shoulder arthroplasties performed using Neer II press-fit
      humeral components and followed for an average of 4.1 years (range, 2-7.8 years)
      were analyzed radiographically. A humeral component was considered
      radiographically at risk for clinical loosening when a radiolucent line > or =2
      mm in width was present in > or =3 zones or tilt or subsidence was identified on
      sequential radiographs by 2 of 3 or 3 of 3 independent observers. Forty
      components (55.6%) were judged to be at risk. There were no identifiable
      characteristics associated with the development of an at-risk humeral component
      except longer average follow-up of the at-risk group (4.7 years vs 3.3 years, P
      =.001). Humeral components at risk had a higher rate of endosteal erosion (P
      =.04) and greater number of zones with sclerosis. Radiographic changes around
      Neer II uncemented humeral components are common. Data from this study can be
      used as 1 benchmark to compare with alternate methods of humeral component
      fixation.

PMID- 11222892
TI  - Total hip arthroplasty in young adults after failed triple innominate osteotomy.
AB  - This study compared the results of total hip arthroplasty (THA) in 11 patients
      with 13 hips who underwent THA after a failed triple innominate osteotomy (TIO)
      with an age-matched and sex-matched group of patients who underwent THA without
      prior TIO. The average age at the time of THA was 37 years (range, 16-50 years).
      The average follow-up of the patients who underwent THA for failed TIO was 36
      months and for the control group was 28 months. One hip in each group underwent
      revision for dislocation. At final follow-up, the average Harris hip score in the
      study group was 76, whereas in the control group it was 88 (P <.05). The pain
      component of the Harris hip score in the study group averaged 32, whereas in the
      control group it averaged 40 (P <.05). Functional scores between the 2 groups
      were similar. Radiographically, there was no difference between the 2 groups.
      Estimated blood loss for the hips performed for failed TIO averaged 721 mL,
      whereas in the control group the estimated blood loss averaged 448 mL (P <.05).
      There was no difference in operative time. The results of this study indicated
      that although the radiographic results of THA after TIO are equivalent to THA
      without prior TIO, clinical results in terms of pain relief and the technical
      difficulty of THA are not equivalent to results in young adult patients who
      undergo THA without prior TIO.

PMID- 11222893
TI  - Unicompartmental knee arthroplasty for lateral gonarthrosis: midterm results.
AB  - Thirty-eight lateral compartment arthroplasties were performed in 22 years.
      Eighteen joints in 17 patients with an average age of 64.5 years were evaluated
      with minimum 5-year follow-up. Using the Hospital for Special Surgery knee score,
      16 of 18 joints had satisfactory results in terms of function and pain relief.
      The average preoperative alignment on standing was 14.9 degrees of valgus
      angulation, which was corrected to 6.9 degrees of valgus. On radiographic
      analysis, no radiolucent lines were seen under the tibial component, but the
      femoral component was loose in 1 joint. Although 5 joints showed slight
      deterioration of osteoarthritic change in the medial compartment, lateral
      compartment arthroplasty is a reliable and successful option in the treatment of
      patients with a low level of physical activity.

PMID- 11222894
TI  - Impaction bone grafting using freeze-dried allograft in revision hip
      arthroplasty.
AB  - We report on 32 patients undergoing revision hip arthroplasty using cemented
      components and impaction allografting with processed freeze-dried bone. The
      survivorship with this type of graft at a mean follow-up of 4 years was 91%.
      There were no femoral component failures, although revision was required in 3
      patients because of failure of the acetabulum. Freeze-dried graft can require
      prolonged rehydration for satisfactory impaction. The results of impaction bone
      grafting with freeze-dried bone alone have been satisfactory, although we
      recommend caution in its use alone in the hostile acetabulum.

PMID- 11222895
TI  - Enhanced soft tissue repair using locking loop stitch after posterior approach
      for hip hemiarthroplasty.
AB  - Hemiarthroplasty of the hip for displaced fracture of the femoral neck (including
      Austin-Moore and Thompson arthroplasties) frequently is performed by orthopaedic
      surgeons. The posterior approach is used despite the slight increase in risk of
      postoperative dislocation. The outcome after dislocation can be disastrous. We
      tried to prevent this complication by repairing the posterior capsule and the
      short external rotators (piriformis, superior and inferior gemellus, obturator
      internus, and upper part of quadratus femoris) using locking loop stitch as
      described by Krackow. From January 1998 to April 1999, 205 hips were operated on
      and followed up for >3 months; no dislocation was found. Using the past records
      as the comparative group, 28 posterior dislocations (1.9%) were found in 1,483
      hip hemiarthroplasties using the posterior approach (P <.05 using exact
      probability test). Enhanced soft tissue repair with locking loop stitch is an
      effective way to reduce the incidence of dislocation after hip hemiarthroplasty
      using the posterior approach.

PMID- 11222896
TI  - Radiologic analysis of the tibial intramedullary canal in Chinese varus knees:
      implications in total knee arthroplasty.
AB  - Seventy-two lower limb long radiographs were reviewed with respect to mechanical
      and anatomic axes. A template of an intramedullary tibial guide rod was employed
      to determine the accuracy of the intramedullary guide in producing ideal tibial
      cuts (ie, 90 degrees ) and acceptable tibial cuts (ie, 90 degrees +/- 2 degrees
      ). The mean difference of the angle formed by the 2 axes was 1.84 degrees +/-
      1.42 degrees. In our findings, 22.2% of patients would have unacceptable cuts if
      an intramedullary device were employed for the tibial cut during a total knee
      arthroplasty. A radiograph showing the whole tibia is required preoperatively to
      identify varus tibiae that are not suitable for the intramedullary method.

PMID- 11222897
TI  - The effect of femoral prosthesis design on cement strain in cemented total hip
      arthroplasty.
AB  - Finite element studies show that the highest cement stresses are located at the
      most proximal and distal ends of the prosthesis. In vitro biomechanical and
      histologic analyses of autopsy-retrieved cemented femoral components show these
      areas to be associated with cement-prosthesis debonding. In this study, cement
      strains were measured in 2 geometrically different femoral stems in paired
      cadaver femora: A straight, collared, moderately tapered stem (Centralign) was
      compared with an anatomically curved, collarless, dramatically tapered stem
      (Scientific Hip Prosthesis [SHP]). Results showed that the maximum strain and the
      overall strain profile differed between the 2 stems. The Centralign had peak
      strains located at the most proximal gauge positions, whereas the peak strains of
      the SHP were located around the middle of the femoral stem. Minimization of
      cement strain, especially at the crucial proximal and distal areas of the stem,
      by altering component design may be able to reduce cement-prosthesis debonding
      and improve clinical results.

PMID- 11222898
TI  - Septic sacroiliitis with hematogenous spread to a total knee arthroplasty.
AB  - Septic sacroiliitis is an uncommon infection that comprises <2% of all
      nontuberculous septic arthritis and osteomyelitis. This case report describes a
      patient with rheumatoid arthritis who developed septic sacroiliitis that
      metastasized to her total knee arthroplasty.

PMID- 11222899
TI  - Periprosthetic high-grade B-cell lymphoma complicating an infected revision total
      hip arthroplasty.
AB  - We report a non-Hodgkin's B-cell lymphoma arising adjacent to a chronically
      infected revision total hip arthroplasty presenting as malignant hypercalcemia 12
      years after original implantation. We believe that this is only the fifth case of
      lymphoma associated with a metal implant to be reported in the English
      literature.

PMID- 11222900
TI  - Dislocation of Insall-Burstein II modified total knee arthroplasty.
AB  - Dislocation of total knee arthroplasty is a rare but serious complication. The
      experience with the Insall-Burstein II modified knee prosthesis, which was
      designed to address the issue of dislocation, has been favorable. We present a
      series of 3 dislocations in 1,500 total knee arthroplasties done with this
      prosthesis, accounting for about 0.2% of cases.

PMID- 11222901
TI  - Early fatigue failures of cemented, forged, cobalt-chromium femoral stems at the
      neck-shoulder junction.
AB  - Femoral component fracture is a rare but well-documented complication after total
      hip arthroplasty. Historically, most stem fractures have occurred at the middle
      third of the implant, where proximal stem loosening and solid distal stem
      fixation result in cantilever bending and eventual fatigue failure. In contrast,
      we report 2 early fatigue failures of well-positioned, well-fixed, cemented,
      forged, cobalt-chromium femoral components at the neck-shoulder junction. A
      contributing factor to the implant failures was heavy laser etching in a region
      of the implant subjected to high stresses, leading to decreased fatigue
      resistance and subsequent fracture.

PMID- 11222902
TI  - Failed cementless total knee arthroplasty presenting as osteolysis of the fibular
      head.
AB  - Large osteolytic lesions can occur adjacent to cementless total knee arthroplasty
      components. This occurrence frequently is related to suboptimal design features
      leading to the generation of metal or polyethylene wear debris. Occasionally,
      such lesions can mimic a bone tumor. A case of a lytic lesion of the fibular head
      adjacent to a failed cementless knee arthroplasty is described along with a
      description of the damaged retrieved component that led to the failure.

PMID- 11222903
TI  - Detection of osteomyelitis using FDG and positron emission tomography.
AB  - A positron emission tomography (PET) scan with 2-[fluorine-18]fluoro-2-deoxy-D
      glucose ((18)FDG) was performed on a patient with clinical and laboratory signs
      of infection after a removed hip prosthesis but with indistinct signs on the bone
      scan and radiographs. The PET scan confirmed the clinical and laboratory signs
      and revealed an unidentified focus of infection in the distal area of the right
      femur.

PMID- 11222904
TI  - Unusual complication associated with femoral intramedullary alignment guide in
      total knee arthroplasty.
AB  - The few reported complications related to the use of a femoral intramedullary
      alignment guide in total knee arthroplasty include increase in perioperative
      bleeding and fat embolism. We report 3 patients suffering from an unusual
      complication, concerning trapping of the tibial locking pin inside the
      intramedullary canal of the femur secondary to the use of an intramedullary
      alignment guide. Methods of retrieving the locking pin from the medullary canal
      are discussed.

PMID- 11222905
TI  - Wavelet domain de-noising of time-courses in MR image sequences.
AB  - Magnetic resonance images acquired with high temporal resolution often exhibit
      large noise artifacts, which arise from physiological sources as well as from the
      acquisition hardware. These artifacts can be detrimental to the quality and
      interpretation of the time-course data in functional MRI studies. A class of
      wavelet-domain de-noising algorithms estimates the underlying, noise-free signal
      by thresholding (or 'shrinking') the wavelet coefficients, assuming the
      underlying temporal noise of each pixel is uncorrelated and Gaussian. A Wiener
      type shrinkage algorithm is developed in this paper, for de-noising either
      complex- or magnitude-valued image data sequences. Using the de-correlation
      properties of the wavelet transform, as elucidated by Johnstone and Silverman,
      the assumption of i.i.d. Gaussian noise can be abandoned, opening up the
      possibility of removing colored noise. Both wavelet- and wavelet-packet based
      algorithms are developed, and the Wiener method is compared to the traditional
      Hard and Soft wavelet thresholding methods of Donoho and Johnstone. The methods
      are applied to two types of data sets. In the first, an artificial set of complex
      valued images was constructed, in which each pixel has a simulated bimodal time
      course. Gaussian noise was added to each of the real and imaginary channels, and
      the noise removed from the complex image sequence as well as the magnitude image
      sequence (where the noise is Rician). The bias and variance between the original
      and restored paradigms was estimated for each method. It was found that the
      Wiener method gives better balance in bias and variance than either Hard or Soft
      methods. Furthermore, de-noising magnitude data provides comparable accuracy of
      the restored images to that obtained from de-noising complex data. In the second
      data set, an actual in vivo complex image sequence containing unknown
      physiological and instrumental noise was used. The same bimodal paradigm as in
      the first data set was added to pixels in a small localized region of interest.
      For the paradigm investigated here, the smooth Daubechies wavelets provide better
      de-noising characteristics than the discontinuous Haar wavelets. Also, it was
      found that wavelet packet de-noising offers no significant improvement over the
      computationally more efficient wavelet de-noising methods. For the in vivo data,
      it is desirable that the groups of "activated" time-courses are homogeneous. It
      was found that the internal homogeneity of the group of time-courses increases
      when de-noising is applied. This suggests using de-noising as a pre-processing
      tool for both exploratory and inferential data analysis methods in fMRI.

PMID- 11222906
TI  - New monoclonal antibody specific for a 6.5 kDa glycoprotein which presents mainly
      on a B cell of chronic lymphocytic leukemia (CLL).
AB  - Chronic lymphocytic leukaemia (CLL) is a most common form of adult leukemia. No
      specific marker for CLL has been defined until today. We attempt to produce a
      specific monoclonal antibody (mAb) to CLL B cells. For this purpose, Balb-C mice
      were immunised with peripheral blood lymphocytes of a patient with CLL. After the
      fusion, the immunised mouse spleen cells and SP2/0 myeloma cell line, antibody
      secreting clones were selected by ELISA and specific antibody was determined by
      flow cytometry. Leukemic cells from different patients, different cell line and
      lymphoid tissue were tested with this mAb using flow cytometry and
      immunoperoxidase methods. Ligand of the mAb on cell surface was identified using
      epitope analysing method. We have shown that this mAb is specific to a molecule
      with 6.5 kDa molecular weight, which is present mainly on B CLL cells (63.7+/
      16.4%). It has also been shown that this molecule was a glycoprotein. Amongst the
      different cell lines that were tested, Raji cell, Molt-3 and P3HR-1 cells were
      expressing this molecule. We, therefore, suggest that it is a novel molecule with
      unknown function and is mainly present on the B cells of CLL.

PMID- 11222907
TI  - Differential expression and secretion of RANTES and MCP-1 in activated peripheral
      blood mononuclear cell cultures of atopic subjects.
AB  - RANTES and MCP-1 represent a link between the activation of monocytes,
      lymphocytes, basophils, mast cells and eosinophils in inflammatory disorders,
      such as the late phase allergic reaction. These C-C chemokines also play a role
      in regulating Th cell cytokine production and leukocyte trafficking. In this
      study, we determined the expression and secretion of RANTES and MCP-1 from PHA
      activated PBMC of healthy and atopic subjects with no symptoms. Levels of RANTES
      from PHA-activated PBMC of atopic patients were higher, at 18 and 24 h
      incubations (42+/-5.5 and 48+/-4), compared to controls (20+/-4 and 35+/-4),
      respectively; while MCP-1 was not (12+/-3 and 17+/-3) compared to controls
      (10.5+/-3 and 15+/-2), respectively. This effect was also revealed on RANTES mRNA
      expression, as determined by reverse transcriptase polymerase chain reaction (RT
      PCR) analysis. In addition, PHA-activated PBMC of atopic subjects produce more IL
      4 (five times more) than healthy subjects, while IFN-gamma did not vary. RANTES,
      compared to MCP-1, may have more influence on signal transduction pathways,
      either in physiologic or inflammatory states and may induce profound effects on
      the regulation of cell activity. The differential production of RANTES and MCP-1
      may lead to diverse regulation of the function and development of cells involved
      in the allergic response. These studies emphasize the importance of chemokine
      selectivity during inflammation.

PMID- 11222908
TI  - Molecular characterization of a monoclonal murine anti-blood group A antibody.
AB  - A mouse monoclonal anti-human blood group A antigen (AC12, mu, kappa) has been
      generated and sequenced in order to analyze the immunoglobulin genes used to
      generate antibodies with anti-human blood group A specificity. Mice were
      immunized with human type A RBC. Anti-A producing hybridomas were detected by
      agglutination against human type A RBC. Total cellular RNA was extracted from
      hybridomas cells. PCR amplification and sequencing of anti-A heavy and light
      chain cDNAs were performed. The VH and VK sequences of antibody AC12 were shown
      to be very homologous to that used by other antibodies recognizing carbohydrates
      as well as glycoproteins, peptides or haptens constituting self antigens as well
      as nonself antigens. The VH sequence of antibody AC12 presented important
      homology with a previously reported monoclonal anti-blood group B antibody. The
      antibody AC12 also presented homology with the VH and VK sequences of a
      previously reported human anti-blood group A antibody which contributes
      additional evidence in favor of a restricted usage of V segments by antibodies
      directed against red blood antigens.

PMID- 11222909
TI  - Production of polyclonal and monoclonal antibodies against CD54 molecules by
      intrasplenic immunization of plasmid DNA encoding CD54 protein.
AB  - DNA immunization, in theory, is of great interest as a source of specific
      antibodies against different antigens. In an attempt to produce polyclonal and
      monoclonal antibodies against cell surface molecules by using the DNA
      immunization strategy, intramuscular and intrasplenic routes of DNA injection
      were compared. Two to five, but not a single, intramuscular DNA immunizations
      induced anti-CD54 and anti-CD147 antibody production. In contrast, a single
      intrasplenic immunization of CD54-encoding DNA could induce anti-CD54 antibody
      production. To produce monoclonal antibody (mAb), spleen cells obtained from an
      intrasplenic CD54-encoding DNA immunized mouse were fused with myeloma cells
      using the standard hybridoma technique. A hybridoma secreting specific mAb to
      CD54 was established. The generated mAb reacted to CD54 protein expressed on
      transfected COS cells and various cell types, the same as using standard CD54 mAb
      MEM-111. Our results demonstrated that direct immunization of antigen-encoding
      DNA into spleen is an effective route for production of both polyclonal and
      monoclonal antibodies to cell surface molecules. This finding is very useful for
      the production of antibodies to cell surface molecules where the protein antigen
      is not available or difficult to prepare, but cDNA encoding the corresponding
      protein is available.

PMID- 11222910
TI  - Cloning of the MHC class II DRB cDNA from the brushtail possum (Trichosurus
      vulpecula).
AB  - The cell-surface glycoproteins encoded by the major histocompatibility complex
      (MHC) bind to processed foreign antigens and present them to T lymphocytes. Two
      classes of MHC molecules and their corresponding gene sequences have been
      extensively studied in eutherian mammals and birds, but data on the marsupial MHC
      are limited. Marsupials split from eutherian mammals about 125 million years ago
      and represent a distinct branch in mammalian evolution. Here the cDNA cloning of
      MHC class II genes of the brushtail possums (Trichosurus vulpecula) is reported.
      The sequences obtained were found to be relatively conserved when compared to the
      red-necked wallaby (Macropus rufogriseus) and an South American marsupial,
      Monodelphis domestica. The T. vulpecula sequence shared an average overall
      sequence identity of 75.4% at the deduced amino acid level with M. rufogriseus
      and M. domestica, respectively.

PMID- 11222911
TI  - HLA class I molecule expression is up-regulated during maturation of dendritic
      cells, protecting them from natural killer cell-mediated lysis.
AB  - It has been widely demonstrated that natural killer (NK) cells are able to
      discriminate between normal and abnormal cells on the basis of the interaction of
      their NKRs with the MHC molecules expressed on the target cells. Recent studies
      showed that also normal dendritic cells are susceptible to NK cell-mediated
      lysis. In this work, the potential relationships between the expression of
      different surface molecules on both immature and mature DC and susceptibility to
      lysis have been investigated. The reduced density of HLA class I on the surface
      of immature DC resulted in the only permissive signal to NK cell mediated
      killing. On the contrary, the remarkable increase in HLA class I molecules
      detected during DC maturation was strictly related to the resistance to NK cell.
      Contemporary, no clear evidences of a role for other surface molecules modulated
      during DC maturation (CD80, CD83, CD86 and CD40), were obtained.

PMID- 11222912
TI  - Decreased CD57 lymphocyte subset in patients with chronic Lyme disease.
AB  - BACKGROUND: Chronic Lyme disease (LD) is a debilitating illness caused by
      tickborne infection with the spirochete Borrelia burgdorferi. Although
      immunologic abnormalities appear to play a role in this disease, specific
      immunologic markers of chronic LD have not been identified. METHODS: We evaluated
      73 patients with chronic LD for lymphocyte subset abnormalities using flow
      cytometry. Of these, 53 patients had predominant musculoskeletal symptoms, while
      20 patients had predominant neurologic symptoms. The estimated duration of
      infection ranged from 3 months to 15 years, and all patients had positive
      serologic tests for B. burgdorferi. Ten patients with acute LD (infection less
      than 1 month) and 22 patients with acquired immunodeficiency syndrome (AIDS)
      served as disease controls. RESULTS: All 31 chronic LD patients who were tested
      prior to antibiotic treatment had significantly decreased CD57 lymphocyte counts
      (mean, 30+/-16 cells per microl; normal, 60-360 cells per microl, P<0.001).
      Nineteen of 37 patients (51%) who were tested after initiating antibiotic therapy
      had decreased CD57 levels (mean, 66+/-39 cells per microl), and all five patients
      tested after completing antibiotic treatment had normal CD57 counts (mean, 173+/
      98 cells per microl). In contrast, all 10 patients with acute LD and 82% of AIDS
      patients had normal CD57 levels, and the difference between these groups and the
      pre-treatment patients with chronic LD was significant (P<0.001). Patients with
      chronic LD and predominant neurologic symptoms had significantly lower mean CD57
      levels than patients with predominant musculoskeletal symptoms (30+/-21 vs. 58+/
      37 cells per microl, P=0.002). CD57 levels increased in chronic LD patients whose
      symptoms improved, while patients with refractory disease had persistently low
      CD57 counts. CONCLUSIONS: A decrease in the CD57 lymphocyte subset may be an
      important marker of chronic LD. Changes in the CD57 subset may be useful to
      monitor the response to therapy in this disease.

PMID- 11222913
TI  - Characterization of hnRNP A2 and B1 using monoclonal antibodies: intracellular
      distribution and metabolism through cell cycle.
AB  - Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 are nuclear RNA binding
      proteins involved in pre-RNA processing. The alternative splicing of the second
      mini exon of A2/B1 gene produces A2 and less abundant B1. It has been reported
      that patients with autoimmune diseases frequently have blood autoantibody valence
      for A2/B1, and recently that the overexpression, especially of B1, is useful for
      detecting cancers in early stage. Three anti-A2/B1 monoclonal antibodies were
      developed using recombinant A2 protein and synthesized peptides around the second
      splicing site. Three antibodies could separately recognize A2 and B1, and their
      specificity made them useful in the study of the biochemical and functional
      properties of A2 and B1. These antibodies have demonstrated differences between
      A2 and B1 in the intracellular distribution and in the metabolism through cell
      cycle. They are valuable reagents to clarify the clinical significance of A2/B1
      in autoimmune diseases and cancers.

PMID- 11222914
TI  - Lysis of autologous macrophages pulsed with hsp10 from Mycobacterium leprae is
      associated to the absence of bacilli in leprosy.
AB  - Peripheral blood mononuclear cells from leprosy patients and normal individuals
      were analysed for their ability to lyse autologous macrophages pulsed with the
      Mycobacterium leprae 10 kDa heat shock protein (hsp10), an antigen considered to
      have an important role in the protective responses in leprosy. Strong cytotoxic
      responses, with an involvement of gammadelta T and class-I and class-II
      restricted alphabeta T cells and/or CD16+56+ cells, were observed in normal
      individuals, paucibacillary (PB) and those multibacillary (MB) patients with
      undetectable bacillary load. On the contrary, only a weak class-II restricted
      cytotoxic response was observed in those MB patients with positive bacillary load
      (MB(+)). Simultaneous addition of IFNgamma plus TNFalpha and IL-12 during hsp10
      stimulation could partially upregulate the low cytotoxic response observed in
      MB(+) by enhancing class-II restricted T cell activity and by development of
      gammadelta T and/or CD16+56+ cell activity. Our results suggest that the ability
      to mount an effective cytotoxic response against hsp10-pulsed macrophages in
      leprosy patients is closely related to the patient's bacterial load and not to
      the clinical form of the disease.

PMID- 11222915
TI  - A clinically approved oral vaccine against pneumotropic bacteria induces the
      terminal maturation of CD83+ immunostimulatory dendritic cells.
AB  - Dendritic cells (DCs) are important antigen-presenting cells of the immune system
      that have attracted interest as cellular adjuvants to induce immunity in clinical
      settings. We have investigated the effects of Broncho-Vaxom, an oral vaccine
      composed of lysates from eight pneumotropic bacteria, on human monocyte-derived
      dendritic cells (moDCs). Broncho-Vaxom induced the terminal maturation of CD83+
      moDCs. MoDCs stimulated with Broncho-Vaxom displayed a phenotype of activated DCs
      with high levels of major histocompatibility complex (MHC) molecules and
      increased levels of adhesion and co-stimulatory molecules. In addition, moDCs
      activated with Broncho-Vaxom exhibited enhanced T cell-stimulatory capacity in
      the allogeneic mixed leukocyte reaction. Broncho-Vaxom at 100 microg/ml was as
      potent as TNF-alpha at 1000 U/ml in activating human moDCs. Neither LPS-like
      activity nor bacterial DNA was found to be responsible for the maturation
      inducing activity of Broncho-Vaxom, suggesting that Broncho-Vaxom contains other
      bacterial factors that are capable of inducing the terminal maturation of moDCs.
      In DC-based immunotherapy, Broncho-Vaxom could be used as a stimulus of DC
      maturation, which meets the standards of good manufacturing practice (GMP). In
      addition, vaccination with Broncho-Vaxom-loaded moDCs may be an attractive
      treatment option in preventing recurrent airway infection in predisposed
      individuals.

PMID- 11222916
TI  - Comparison of ketamine stereoisomers on tissue metabolic activity in an in vitro
      model of global cerebral ischaemia.
AB  - Ketamine (2-o-chlorophenenyl-2-methylaminocyclohexanone hydrochloride) is a
      dissociative general anaesthetic with neuroprotective properties. Since ketamine
      is optically active, we compared the neuroprotective efficacy of the (+)- or (-)
      enantiomers in global cerebral ischaemia. Rat corticostriatal slices superfused
      with, or incubated in, artificial CSF at 34 degrees C were subjected to a brief
      ischaemic insult. Dopamine efflux was measured using fast cyclic voltammetry.
      Tissue metabolism was determined with 2,3,5-triphenyltetrazolium chloride
      staining, a marker of mitochondrial enzyme activity. In control slices, ischaemia
      caused rapid striatal dopamine release (to 122 microM over 18 s) after an initial
      delay of 149s. Racemic ketamine (100 micromol/l) significantly delayed (by 24%,
      P<0.05), slowed (by 63%, P<0.01) and reduced (by 27%, P<0.05) ischaemia-induced
      dopamine release. Ischaemia (10 min) also caused significant decreases in
      striatal (25%, P<0.01) and cortical (31%, P<0.001) metabolic activity, manifested
      as a drop in mean TTC staining intensity. Racemic ketamine and its (+)- and (-)
      enantiomers (each 100 microM) attenuated the loss of metabolic activity in the
      striatum. However, in the cortex, only (+)-ketamine (100 microM) was
      significantly neuroprotective. We conclude that neuroprotection by ketamine in
      cerebral ischaemia is both region- and isomer-dependent.

PMID- 11222917
TI  - Acquisition of blood--tissue barrier--supporting features by hepatic stellate
      cells and astrocytes of myofibroblastic phenotype. Inverse dynamics of
      metallothionein and glial fibrillary acidic protein expression.
AB  - A number of similarities between astrocytes and hepatic stellate cells (HSC) rose
      the question whether or not the protective barrier features of blood-tissue
      interface may be provided by HSC as well. To test this hypothesis, we
      investigated the presence of metallothionein (MT), a functional marker of blood-
      brain barrier, in HSC in situ and in cell culture and compared the results with
      those obtained with astrocytes. The dynamics of MT expression in cultured
      astrocytes and HSC was investigated by simultaneous labelling of the cells with a
      monoclonal antibody (MAb MT) against a lysine-containing epitope of the cadmium
      induced monomer of MT-I from rat liver and antiserum against glial fibrillary
      acidic protein (GFAP). Cell activation was estimated by the presence of smooth
      muscle alpha-actin (SMAA). In immunoblotting, MAb MT recognized monomeric MT
      protein and proteins in the 30-kDa range; both bands were pronounced in brain and
      barely visible in liver homogenates. In situ, MAb MT reacted with very few
      perivascular cells situated in the parenchyma of the liver. Double
      immunolabelling of brain slices with MAb MT and antiserum against GFAP showed
      large areas of brain containing cells expressing both MT and GFAP. However, there
      were also regions in the brain where the cells produced solely GFAP or MT. In
      liver cell culture, MT was absent from HSC and hepatocytes in early periods of
      cultivation, during which the cells maintained their original features; however,
      MT was expressed strongly in HSC during their activation under prolonged culture
      conditions. Inversely, in astrocytes MT was expressed during early culturing and
      disappeared from the cells together with SMAA in late culture when GFAP was
      upregulated. These results suggest that the acquisition of myofibroblastic
      features by perivascular cells empowers them to establish a protective blood
      tissue permeability barrier. In addition, this study shows that, at least in cell
      culture, an enrichment of perivascular cells in GFAP results in the disappearance
      of protective functions.

PMID- 11222918
TI  - Retinal glutamate in diabetes and effect of antioxidants.
AB  - Diabetes results in various biochemical abnormalities in the retina, but which of
      these abnormalities are critical in the development of retinopathy is not known.
      The aim of this study is to examine the effect of antioxidant supplementation on
      diabetes-induced alterations of retinal glutamate, and to explore the inter
      relationship between alterations of retinal glutamate, oxidative stress, and
      nitric oxide (NO) in diabetes. Glutamate was measured in the retina at 2 months
      of diabetes in rats receiving diets supplemented with or without a mixture of
      antioxidants containing ascorbic acid, Trolox, DL alpha-tocopherol acetate, N
      acetyl cysteine, beta-carotene and selenium. The relationship between glutamate,
      oxidative stress and NO was evaluated using both bovine retinal endothelial cells
      and normal rat retina. In diabetes, retinal glutamate was elevated by 40,
      thiobarbituric acid-reactive substances (TBARS) by 100, and NO by 70%,
      respectively. Administration of antioxidants inhibited the diabetes-induced
      increases in glutamate, TBARS and NO. Incubation of bovine retinal endothelial
      cells or normal rat retina with glutamate significantly increased TBARS and NO,
      and addition of either antioxidant (N-acetyl cysteine) or a NO synthase inhibitor
      prevented the glutamate-induced elevation in oxidative stress and NO. Incubation
      of retina with a glutamate agonist, likewise elevated oxidative stress and NO,
      and memantine inhibited such elevations. Thus, the alterations of retinal
      glutamate, oxidative stress and NO appear to be inter-related in diabetes, and
      antioxidant therapy may be a suitable approach to determine the roles of these
      abnormalities in the development of diabetic retinopathy.

PMID- 11222919
TI  - Effect of an adenosine A(1) receptor agonist and a novel pyrimidoindole on
      membrane properties and neurotransmitter release in rat cortical and hippocampal
      neurons.
AB  - Activation of adenosine A(1) receptors by endogenous adenosine plays a
      neuroprotective role under various pathophysiological conditions including
      hypoxia. Intracellular recordings were made in rat pyramidal cells of the
      somatosensory cortex. Hypoxia (5 min) induced a membrane depolarization and a
      decrease of input resistance. The A(1) receptor agonist N(6)-cyclopentyladenosine
      (CPA, 100 microM) reversibly inhibited the hypoxic depolarization. The inhibition
      was also present after blockade of the A(2A), A(2B) and A(3) receptor subtypes by
      selective antagonists. CPA had no effect on the hypoxic decrease of input
      resistance. 1,3-Dipropyl-8-cyclopentylxanthine (DPCPX), a selective A(1) receptor
      antagonist, which did not alter hypoxic depolarization when given alone abolished
      the inhibitory effect of CPA. Neither CPA nor DPCPX influenced membrane potential
      or apparent input resistance under normoxic conditions. The novel pyrimidoindole
      (R)-9-(1-methylbenzyl)-2-(4'-pyridyl)-9H-pyrimido[4,5-b]indole-4-amine (APPPI, 1
      and 10 microM) reversibly diminished hypoxic depolarization but had no
      significant effect on input resistance. The effect of APPPI at a concentration of
      1 microM, but not at 10 microM, was blocked by DPCPX (0.1 microM). CPA (100
      microM) inhibited [(3)H]-noradrenaline ([(3)H]-NA) release from rat hippocampal
      brain slices significantly only in the presence of rauwolscine (0.1 microM), an
      alpha(2)-adrenoceptor antagonist. APPPI (1 and 10 microM) exhibited an inhibitory
      effect similar to that observed with CPA. The effects of both CPA and APPPI were
      antagonized by DPCPX (0.1 microM). The present data suggest that mainly
      presynaptic mechanisms prevent neurons from hypoxic changes by an inhibition of
      transmitter release. However, in contrast to CPA, APPPI exhibited additional
      effects, which require further investigation.

PMID- 11222920
TI  - Metabolism of [1-(13)C)glucose and [2-(13)C]acetate in the hypoxic rat brain..
AB  - The effects of hypoxia on the metabolism of the central nervous system were
      investigated in rats submitted to a low oxygen atmosphere (8% O(2); 92% N(2)). [1
      (13)C]glucose and [2-(13)C]acetate were used as substrates, this latter being
      preferentially metabolized by glial cells. After 1-h substrate infusion, the
      incorporation of 13C in brain metabolites was determined by NMR spectroscopy.
      Under hypoxia, an important hyperglycemia was noted. As a consequence, when using
      labeled glucose, the specific enrichment of brain glucose C1 was lower (48.2+/
      5.1%) than under normoxia (66.9+/-2.5%). However, relative to this specific
      enrichment, the (13)C incorporation in amino acids was increased under hypoxia.
      This suggested primarily a decreased exchange between blood and brain lactate.
      The glutamate C2/C4 enrichment ratio was higher under hypoxia (0.62+/-0.01) than
      normoxia (0.51+/-0.06), indicating a lower glutamate turnover relative to the
      neuronal TCA cycle activity. The glutamine C2/C4 enrichment ratio was also higher
      under hypoxia (0.87+/-0.07 instead of 0.65+/-0.11), indicating a new balance in
      the contributions of different carbon sources at the acetyl-CoA level. When using
      [2-(13)C]acetate as substrate, no difference in glutamine enrichment appeared
      under hypoxia, whereas a significant decrease in glutamate, aspartate, alanine
      and lactate enrichments was noted. This indicated a lower trafficking between
      astrocytes and neurons and a reduced tricarboxylic acid cycle intermediate
      recycling of pyruvate.

PMID- 11222921
TI  - Cyclosporin A-sensitive signaling pathway involving calcineurin regulates
      survival of reactive astrocytes.
AB  - Calcineurin, a ubiquitous calcium-activated serine phosphatase, plays an
      important role in the signal transduction. We have previously reported that
      cyclosporin A (CsA) inhibits the growth and survival of the rat C6 glioma cells
      due to the inhibition of signaling pathway involving calcineurin and
      transcription factor nuclear factor of activated T cells (NFAT). In the present
      study, we show that CsA affects the survival of reactive astrocyte cultures
      derived from striatal trauma. Exposure of reactive astrocytes to doses of CsA >50
      microg/ml for 24--72 h produces morphological changes, including cell body
      shrinkage and loss of extensions, followed by cell death. This death was
      accompanied by apoptotic changes in nuclear morphology and DNA fragmentation, as
      revealed by Hoechst 33258 and positive TUNEL staining. We demonstrated the
      presence of calcineurin A subunit in reactive astrocytes and corpus callosum
      (brain structure enriched in astrocytes) and an additional calcineurin-like
      protein occurring solely in reactive astrocytes. FK506, a calcineurin inhibitor
      unrelated to CsA, inhibits proliferation of astrocytes and induces death
      accompanied by apoptotic changes in nuclear morphology and DNA fragmentation.
      Since calcineurin is a major target for both CsA and FK506, the results suggest
      that this phosphatase is involved in the regulation of reactive astrocyte
      survival.

PMID- 11222922
TI  - Antinociceptive effect of spinally injected L-NAME on the acute nociceptive
      response induced by low concentrations of formalin.
AB  - The formalin test has been proposed as an animal model of pain produced by tissue
      injury. Although biphasic nociceptive responses to formalin injection have been
      well documented, low concentrations (0.125 and 0.5%) of formalin injected into
      the mouse hindpaw produced only the phasic (acute) paw-licking response, lasting
      the first 5 min after the formalin injection. To explore the involvement of
      nitric oxide (NO) in the spinal cord and peripheral system during the acute phase
      of the formalin test, we examined the effect of intrathecal (i.t.) or
      intraplantar (i.pl.) injection of L-N(G)-nitro arginine methyl ester (L-NAME), a
      NO synthase inhibitor in mice. Pretreatment with L-NAME (160 nmol), injected
      i.t., resulted in a significant inhibition of the paw-licking response induced by
      0.125 and 0.5% of formalin. L-Arginine (600 mg/kg, i.p.) but not D-arginine (600
      mg/kg, i.p.) reversed the antinociceptive effect of L-NAME on the acute
      nociceptive response induced by low concentrations of formalin. The i.pl.
      injection of L-NAME (160 nmol) produced a significant decrease of the late
      (tonic) phase response evoked by 2.0% formalin without affecting the early
      (acute) phase response. Similar results have been reported in the case of i.t.
      injected L-NAME as assayed by the 2.0% formalin test. L-NAME (160 nmol), injected
      into the plantar paw, gave no significant effect on the acute nociceptive
      response induced by a low concentration of formalin (0.125%). These results
      suggest that NO in the spinal cord may be involved in not only the late phase
      response of the formalin (2.0%)-induced paw-licking, but also at least the acute
      phase response induced by low concentrations (0.125 and 0.5%) of formalin, while
      peripheral NO has little effect on the early (acute) phase nociceptive response
      evoked by formalin (0.125--2.0%) injection.

PMID- 11222923
TI  - Protein thiol oxidation by haloperidol results in inhibition of mitochondrial
      complex I in brain regions: comparison with atypical antipsychotics.
AB  - Usage of 'typical' but not 'atypical' antipsychotic drugs is associated with
      severe side effects involving extrapyramidal tract (EPT). Single dose of
      haloperidol caused selective inhibition of complex I in frontal cortex, striatum
      and midbrain (41 and 26%, respectively) which was abolished by pretreatment of
      mice with thiol antioxidants, alpha-lipoic acid and glutathione isopropyl ester,
      and reversed, in vitro, by disulfide reductant, dithiothreitol. Prolonged
      administration of haloperidol to mice resulted in complex I loss in frontal
      cortex, hippocampus, striatum and midbrain, while chronic dosing with clozapine
      affected only hippocampus and frontal cortex. Risperidone caused complex I loss
      in frontal cortex, hippocampus and striatum but not in midbrain from which
      extrapyramidal tract emanates. Inhibition of the electron transport chain
      component, complex I by haloperidol is mediated through oxidation of essential
      thiol groups to disulfides, in vivo. Further, loss of complex I in extrapyramidal
      brain regions by anti-psychotics correlated with their known propensity to
      generate side-effects involving extra-pyramidal tract.

PMID- 11222924
TI  - Effects of L-glutamate, D-aspartate, and monensin on glycolytic and oxidative
      glucose metabolism in mouse astrocyte cultures: further evidence that glutamate
      uptake is metabolically driven by oxidative metabolism.
AB  - The hypothesis was tested that oxidative metabolism, mainly fueled by glutamate
      itself, provides the energy for active, Na(+),K(+)-ATPase-catalyzed Na(+)
      extrusion following glutamate uptake in conjunction with Na(+). This hypothesis
      was supported by the following observations: (i) glutamate had either no effect
      or caused a slight reduction in glycolytic rate, measured as deoxyglucose
      phosphorylation; (ii) D-aspartate, which is accumulated by the L-glutamate
      carrier, but cannot be metabolized by the cells, caused an increase in glycolytic
      rate; (iii) monensin which, like D-aspartate, stimulates the intracellular, Na(+)
      activated site of the Na, K-ATPase and thus energy metabolism, but provides no
      metabolic substrate, stimulated both glycolysis and glucose oxidation; and (iv)
      oxidation of glucose was potently inhibited by glutamate, although glutamate is
      known to stimulate oxygen consumption in primary cultures of astrocytes, a
      combination showing that oxidation of a non-glucose substrate is increased in the
      presence of glutamate. These findings should be considered in attempts to
      understand metabolic interactions between neurons and astrocytes and regulation
      of energy metabolism in brain.

PMID- 11222925
TI  - Okadaic acid and cyclosporin A modulate [(3)H]GABA release from rat brain
      synaptosomes.
AB  - Rat brain synaptosomes were used to investigate the effect of okadaic acid, an
      inhibitor of protein phosphatase 1 and 2A, and cyclosporin A, an inhibitor of
      protein phosphatase 2B (calcineurin), on [(3)H]GABA release. Release of
      [(3)H]GABA was evoked by 4-aminopyridine in the presence of calcium and by alpha
      latrotoxin in the presence and absence of calcium. Pretreatment of synaptosomes
      with 1 microM okadaic acid reduced [(3)H]GABA release evoked by 4-aminopyridine
      by about 40%. The effect of alpha-latrotoxin on [(3)H]GABA release was stimulated
      by okadaic acid. This stimulation was equal in both media. The stimulating effect
      of 4-aminopyridine and alpha-latrotoxin on [(3)H]GABA release was activated when
      synaptosomes were pretreated with cyclosporin A. Activation of 4-aminopyridine
      evoked [(3)H]GABA release was observed at 1 microM cyclosporin A, but the toxin
      effect was enhanced only when concentration of cyclosporin A was increased to 10
      microM. The level of cyclosporin A activation depended on alpha-latrotoxin
      concentrations used - a higher stimulating effect of cyclosporin A was observed
      with lower toxin concentration. These results suggest that in calcium medium 4
      aminopyridine- and alpha-latrotoxin-evoked [(3)H]GABA release was realized by
      different mechanisms.

PMID- 11222926
TI  - Cultured astrocytes react to LPS with increased cyclooxygenase activity and
      phagocytosis.
AB  - Phagocytosis and prostaglandin E(2) production were investigated in purified
      cultures of perinatal rat forebrain astrocytes. Light and electron microscopic
      data indicated that astrocytes respond to bacterial endotoxin, lipopolysaccharide
      (LPS) by increased phagocytosis and by activating the cyclooxygenase enzyme
      pathway. LPS-inducible phagocytosis of astrocytes was demonstrated by electron
      microscopic studies on colloidal gold uptake and by photometric determination of
      fluorescent bead ingestion. The internalisation of fragments of the plasma
      membrane was shown by histochemical detection of membrane-bound ecto-ATPase
      activity within intracellular vesicles. Activation of the cyclooxygenase pathway,
      a characteristic reaction of immune cells under inflammatory conditions, was also
      detected in astroglial cells upon treatment with LPS. The increased prostaglandin
      E(2) (PGE(2)) production by astrocytes in response to LPS was reduced by the non
      steroid anti-inflammatory drug, indomethacin. Our data indicate that astrocytes
      display some tissue-protective reactions in response to inflammation inducing
      factors, even in the absence of peripheral immune cells or central microglia. The
      role of inducible astrocytic phagocytosis in a non-immune protection-pathway is
      discussed.

PMID- 11222927
TI  - Passive extensibility of skeletal muscle: review of the literature with clinical
      implications.
AB  - The purpose of this article was to review the literature on passive extensibility
      of skeletal muscle with reference to its anatomic and physiologic properties,
      mechanisms of adaptations and clinical implications. Studies with animal muscles
      have shown that passive extensibility is influenced by the size (mass) and length
      of muscle fibers, and the amount and arrangement of the connective tissues of the
      muscle belly. The resistance to passive lengthening is influenced by the readily
      adaptable amount of muscle tissue, including the contractile proteins and the non
      contractile proteins of the sarcomere cytoskeletons. The relationship of
      adaptable changes in the muscle tissue and in the extracellular connective
      tissues remains unclear. Muscle length adaptations result from changes in the
      number of sarcomeres in series, which depend on the imposed length of muscles,
      not on the level of muscle activation and tension. This mechanism of muscle
      length adaptations, termed 'myogenic', has not been demonstrated in human
      muscles, but it has been intimated by therapeutic lengthening studies showing
      that both healthy and neurologically impaired human muscles can undergo increased
      length adaptations in the presence of muscle activations. Studies have suggested
      that optimal muscle function is probably achieved by increasing muscle length,
      length extensibility, passive elastic stiffness, mass and strength, but
      additional studies are needed to investigate these relationships, particularly
      for aged muscles and for muscles affected by clinical disorders, disease and
      injury. Such studies could contribute to the development of new intervention
      strategies designed to promote the passive muscle extensibility that enhances
      total muscle function, and ultimately improves the ability to complete functional
      activities and excel in athletic performances.

PMID- 11222928
TI  - Neuromuscular neutral zones sensitivity to lumbar displacement rate.
AB  - OBJECTIVES: To determine the displacement and tension thresholds (developed
      during anterior lumbar flexion) which trigger reflexive muscular activity in the
      multifidus muscles; their variability with the velocity of flexion; and the
      pattern of threshold variability across the lumbar spine.Design. An in-vivo study
      of the feline during passive lumbar flexion applied via the L-4/5 supraspinous
      ligament. METHOD: EMG from six pairs of intramuscular electrodes inserted in the
      L-1/2 to L-6/7 multifidus muscles was recorded while the lumbar spine was
      passively flexed to 75% of the physiological strain of the supraspinous ligament
      at rates of 17-100%/s. Three-dimensional models of tension threshold, flexion
      rate and lumbar levels were developed from the experimental data. RESULTS:
      Displacement and tension thresholds were the lowest at the fastest flexion rate
      and gradually increased as flexion rates decreased. Electromyographic activity
      was detected at low thresholds at the center of the flexion and at gradually
      increasing thresholds at higher and lower lumbar segments. CONCLUSION: Multifidus
      reflexive muscular activity, which stabilize the spine, is triggered at a
      displacement and tension thresholds of 5-15% of the physiological range. Earlier
      activation of muscular activity occurs as the velocity of flexion increases.
      Earlier activation also occurs near the center of flexion. RELEVANCE: Sensory
      motor neurological feedback maintains spine stability and is responsive to the
      velocity of lumbar motion. A neuromuscular silence exists in small lumbar
      movements in which spine stability is not protected by the musculature. Spine
      models constructed to predict risk factors could benefit from incorporating this
      new information.

PMID- 11222929
TI  - Symmetry and linearity of trunk function in subjects with non-specific low back
      pain.
AB  - Objective. To investigate the effect of a standard rehabilitation program on the
      symmetry of trunk kinematics in subjects with non-specific low back pain.Design.
      Assessing lumbar spine kinematics in the cardinal planes using
      dynamometry.Background. Previous evaluations of trunk symmetry focussed more on
      anatomical rather than functional symmetry. Correlation of functional symmetry
      with low back pain was occasionally performed, but only for base line
      evaluations. To the best of the author's knowledge, there is no study examining
      the effect of exercise on the functional symmetry of the trunk, especially in non
      specific low back pain subjects.Methods. Two groups of young male subjects whose
      working conditions incurred long daily hours of sitting and standing participated
      in the study. Muscles of the lumbar spine were initially evaluated in the
      cardinal planes using dynamometry. The same parameters (maximum isometric torque,
      dynamic torque, angular velocity and range of motion) were then repeatedly
      measured throughout a standardized strength protocol lasting for 12 sessions over
      a four-week period.Results. As pain gradually disappeared over a one-month period
      of rehabilitation, certain factors of the trunk kinematics exhibited convergence
      towards perfect symmetry while others showed oscillations. Moreover, global right
      left data for certain trunk kinematics exhibited near-perfect linear
      relationship.Conclusion. Functional symmetry of the trunk in the coronal and
      transverse planes can be used to assess the progress of rehabilitation programs
      of non-specific low back pain subjects. RelevanceRehabilitation programs focus on
      the progress of directly measured trunk kinematics, which do not always exhibit
      monotonic behavior. This paper alludes to the importance of tracking symmetry of
      trunk kinematics as it may help clinicians modify the strengthening protocols in
      order to achieve more rapid relief from back pain.

PMID- 11222930
TI  - The effect of partial removal of the nucleus pulposus from the intervertebral
      disc on the response of the human annulus fibrosus to compression.
AB  - OBJECTIVE: To determine how partial removal of the nucleus changes the response
      of the annulus to compression. DESIGN: The deformation of the annulus in the mid
      sagittal plane, during compression, was determined from digital video images.
      BACKGROUND: Several studies have shown that removal of the nucleus changes the
      external behaviour of the intervertebral disc, but few studies have investigated
      changes to internal behaviour. METHODS: Six frozen human lumbar discs were
      bisected in the sagittal plane to produce 12 specimens. The cut surfaces were
      marked with seven dots of Alcian blue stain. The specimens were sealed, enabling
      their internal structure to be viewed directly by a digital video recording
      system, and thawed. The video system recorded the response of each specimen as it
      was compressed by up to 1.8 mm at a rate of 0.2 mm s(-1). The displacements of
      the Alcian blue marks were measured using an image analysis program. Magnetic
      resonance imaging was used to investigate the validity of this technique.
      RESULTS: Partial removal of the nucleus changed the way that the disc deformed
      under compression. A highly significant change in direction of movement was seen
      in the inner posterior region of the annulus. CONCLUSIONS: Partial removal of the
      nucleus changes the response of the annulus to compression. RELEVANCE: Partial
      denucleation of the human intervertebral disc is shown to change the direction of
      bulging of the inner annulus when the disc is compressed. Increases in shear
      stress, arising from these changes, may lead to further disc degeneration in the
      form of circumferential tears.

PMID- 11222931
TI  - In vivo geometrical evaluation of Cheneau-Toulouse-Munster brace effect on
      scoliotic spine using MRI method.
AB  - OBJECTIVES: The aim was to quantify the immediate effect of the Cheneau-Toulouse
      Munster brace (worn at night) on scoliotic curvatures in vivo.Design. A three
      dimensional geometrical model of the spine was developed using magnetic resonance
      images. BACKGROUND: Many corrective ortheses were proposed for the orthopaedic
      treatment of idiopathic scoliosis. Simple radiographs were not sufficient to
      analyse the three-dimensional spinal deformations. So, three-dimensional
      geometrical models were developed using stereoradiography and axial tomography.
      MRI has been only used clinically for investigation of intervertebral disc
      disorders. METHOD: MRI examination had been performed on 14 girls having an
      idiopathic scoliosis and wearing a first Cheneau-Toulouse-Munster brace. The
      protocol investigated was performed with and without brace. Using an in-house
      image processing software and the pre-post processing software Patran, two
      geometrical models of the spine (spine without brace and spine with brace
      correction) were obtained, respectively, for each patient, the models including
      the vertebral bodies. RESULTS: Our method reproducibility was found to be 0.5 mm
      on the displacements and 2.5 degrees on the rotations. The Cheneau-Toulouse
      Munster brace decreased the coronal shift forward, the coronal tilt, the axial
      rotation, and increased the sagittal shift forward and the sagittal vertebral
      tilt. DISCUSSION: The results showed that the Cheneau-Toulouse-Munster brace had
      a three-dimensional and personalised action on vertebrae. This technique using
      MRI provides no irradiation and allows the soft tissue visualisation, but
      actually is not dedicated for clinical use and is limited to the lying position.
      RELEVANCE: The qualitative and quantitative data obtained allowed a better
      description of the Cheneau-Toulouse-Munster brace effect on scoliotic spine, and
      will help the orthopaedist in the brace design and the clinician in the scoliosis
      comprehension.

PMID- 11222932
TI  - Dynamic inferior stabilizers of the shoulder joint.
AB  - BACKGROUND: The glenohumeral joint is soft-tissue balanced. However, few studies
      have focused on its dynamic inferior stabilizers. OBJECTIVE: The objective of
      this study was to investigate the dynamic contributions of five shoulder muscles
      to inferior stability of the glenohumeral articulation in four joint positions.
      METHODS: The anterior, lateral and posterior deltoid, supraspinatus, short head
      of biceps, coracobrachialis and long head of triceps from ten cadaveric shoulders
      were tested in 0 degrees, 30 degrees, 60 degrees and 90 degrees of glenohumeral
      abduction. A constant inferior force of 15 N was applied to the humerus. The
      tendons were loaded sequentially in proportion to their respective muscle's cross
      sectional area. Translations of the humeral head on the glenoid were recorded
      with a 3-Space tracking device. RESULTS: The lateral deltoid (8.2 mm, SD 4.8 mm)
      was potentially most effective in superior translation of the humeral head
      followed by the posterior deltoid (7.7 mm, SD 4.8 mm). The coracobrachialis and
      short head of biceps had considerable capability to translate the humeral head
      superiorly (2.8 mm, SD 1.3 mm) while the supraspinatus showed the weakest effects
      (1.3 mm, SD 0.5 mm). RELEVANCE: Strengthening exercises of the deltoid may be
      useful in the treatment of inferior glenohumeral instability, while the
      supraspinatus seems to be less important for inferior glenohumeral stability than
      previously assumed.

PMID- 11222933
TI  - Loosening performance of cemented glenoid prosthesis design pairs.
AB  - OBJECTIVE: The purpose of this pilot study (n=3) was to compare the loosening
      performance of glenoid prosthesis design pairs where only one design variable
      differed. DESIGN: Glenoids were subjected to dynamic edge loading in a biaxial
      test setup. BACKGROUND: Glenoid component loosening is the primary concern in
      total shoulder arthroplasty. METHODS: After the humeral head was cycled 100,000
      times to the superior and inferior edges of the glenoid, the tensile edge
      displacements were measured under superior and inferior off-center loading.
      RESULTS AND CONCLUSIONS: Based on this study, a rough-backed design had
      dramatically better loosening performance than a smooth-backed; curved-backed was
      superior to flat-backed; a less-constrained articular surface was better than a
      more-constrained articular surface; pegs outperformed a keel; threaded pegs were
      marginally preferable to cylindrical pegs; and an all-polyethylene design rocked
      slightly less than a metal-mesh-backed design. RELEVANCE: A comparison of the
      laboratory loosening behavior of glenoid prostheses may lead to improved designs,
      subsequently leading to a reduction in the incidence of clinical loosening.

PMID- 11222934
TI  - Rapid application fracture fixators - an evaluation of mechanical performance.
AB  - OBJECTIVE: This study evaluates the mechanical performance of the Pinless and
      Centrafix fixators for rapid application to tibial fractures in a disaster or
      battlefield scenario. DESIGN: Comparative study based on measurements made in the
      laboratory. BACKGROUND: The Pinless and Centrafix fixators may be considered for
      rapid application to stabilise fractures in emergency conditions without the aid
      of electrical equipment such as power drills for bone screw insertion or image
      intensifiers to facilitate bone alignment. METHODS: Stiffnesses, maximum service
      loads and fatigue strengths of the fixators were measured in the orientations of
      loading that correspond to walking and stretcher-bearing. These properties were
      compared with measurements on three conventional fixators, the AO, Shearer and
      Triax. RESULTS: The Centrafix stiffnesses were 31 N/mm (axial), 1 N/ degrees
      (torsional shear), 0.4 N/ degrees (coronal plane bending), 4 N/ degrees (sagittal
      plane bending) and 11 N/mm (transverse shear) and strengths were 95 N (axial) and
      1.9 Nm (bending). Corresponding Pinless stiffnesses were 43 N/mm, 0.7 N/ degrees,
      0.3 N/ degrees, 8 N/ degrees and 50 N/mm, and strength was 55 N (axial).
      CONCLUSIONS: The stiffness and strength of both rapid application fixators in
      simulated walking was judged to be low, and additionally the stiffness and
      strength of the Centrafix in simulated stretcher-bearing was judged to be low.
      RELEVANCE: The Pinless is not recommended for weight-bearing subjects with
      unstable fractures. The Centrafix is not recommended for stretcher-bearing or
      weight-bearing with unstable fractures.

PMID- 11222935
TI  - The influence of inserting a Fuji pressure sensitive film between the
      tibiofemoral joint of knee prosthesis on actual contact characteristics.
AB  - OBJECTIVE: To investigate the influence of inserting a Fuji pressure sensitive
      film between the tibiofemoral joint of knee prosthesis on actual contact
      characteristics. DESIGN: A finite element analysis was used to investigate the
      alteration of contact characteristics of the tibiofemoral joint due to inserting
      a pressure sensitive film between the contacting surfaces. BACKGROUND: The
      discrepancy between actual contact behaviors of tibiofemoral joint of knee
      prosthesis and the measurement using Fuji pressure sensitive film was not
      discussed extensively. The change of direct contact circumstance of the
      tibiofemoral joint due to inserting a pressure sensitive film was not well
      reported. METHOD: A two-dimensional finite element model of the tibiofemoral
      joint of knee prosthesis in the sagittal plane was constructed. Four different
      radii of the femoral component were used to investigate the conformity effect.
      Two-layers of plane strain element were used to model the pressure sensitive
      film. The influence of inserting a pressure sensitive film on the actual contact
      characteristics was analyzed by comparing the results of the change in contact
      radius. RESULTS: Inserting a pressure sensitive film between contacting surfaces
      would disturb the original contact behaviors, especially in the lowest conformity
      design. The maximum difference of contact radius between the model simulating
      actual contact circumstance and the model with inserting a pressure sensitive
      film between contacting surface was 77% in the lowest conformity condition at the
      smallest load. CONCLUSIONS: This study proposes a quantitative analysis of
      contact characteristics in the tibiofemoral joint of knee prosthesis between the
      models with and without inserting a pressure sensitive film into the contact
      surface. The measurement of contact area in artificial tibiofemoral joints by
      using Fuji pressure sensitive film is always overestimated its true contact area
      by 14-77%. RELEVANCE: This study revealed the measurement of contact
      characteristics of artificial tibiofemoral joints by using Fuji pressure
      sensitive film which depends on not only the applied load, but also the
      conformity and material properties of the contact surface. Therefore, the
      information of the conformity and material properties of the contact surface
      should be provided as well as the applied load wherever a measurement of contact
      characteristics using Fuji pressure sensitive film is analyzed and interpreted.

PMID- 11222936
TI  - Effect of slip on movement of body center of mass relative to base of support.
AB  - OBJECTIVE: The purpose is to investigate the effect of balance conditions and
      slippery perturbation on the position and velocity of the body's center of mass
      relative to the body's base of support. DESIGN: Twenty-two young and healthful
      subjects were investigated while their walk was perturbed by a soap patch applied
      over a force plate. A safety harness was used to prevent the subject from falling
      on knee or buttock. BACKGROUND: Appropriate postural response to meet
      physiological biomechanical requirements is mandatory in restoration of balance
      upon slip. METHODS: Twenty-two healthy subjects dressed with safety harness
      walked first without and then with slippery perturbation, guided by a metronome
      at 120 steps/min and 90 steps/min cadence. Data were collected from a motion
      analysis system and force plates. RESULTS: For slippery perturbation, the
      displacement and velocity of center of mass with respect to base of support
      became smaller from heel strike to contralateral toe off. Subject's balance
      condition correlated significantly to the displacement of center of mass with
      respect to base of support (r=-0.51 at 120 steps/min and r=-0.471 at 90
      steps/min), as well as the velocity (r=-0.834 at 120 steps/min, r=-0.673 at 90
      steps/min) at contralateral toe off. CONCLUSIONS: For slip during walking,
      smaller excursion and faster velocity of center of mass with respect to base of
      support were important for subjects regaining balance from heel strike to
      contralateral toe off. The critical time for subjects regaining stability is the
      first double support phase of the gait cycle. RELEVANCE: It is confirmed that two
      variables, the displacement and the velocity of center of mass with respect to
      base of support, are valuable biomechanical factors and provide quantifiable
      determination for investigation of the balance condition in slipping.

PMID- 11222937
TI  - A novel function of 20-hydroxyecdysone: translational repression of the lysosomal
      protease mRNA in the mosquito fat body.
AB  - In the female fat body of the mosquito Aedes aegypti, lysosomes play important
      roles during the cessation of vitellogenesis by degrading the biosynthetic
      machinery and aiding the remodeling of the fat body cells. A detailed study of a
      mosquito lysosomal aspartic protease (AaLAP) has shown a unique expression
      pattern in the vitellogenic fat body: the level of AaLAP mRNA dramatically rises
      and peaks at 24 h post blood meal (PBM) correlating with the high titer of
      ecdysteroids; however, there is a 12 h lag before peak levels of AaLAP protein
      and its enzymatic activity has been observed. These observations suggest that the
      high titer of 20-hydroxyecdysone (20E) may hinder translation of the AaLAP mRNA.
      Here, we used an in vitro organ culture to study the effect of 20E on the protein
      synthesis of AaLAP in the fat body. The increase in the AaLAP protein level in
      the fat body, dissected at 24 h PBM and incubated for 6 or 12 h, was inhibited by
      the presence of 10(-5) M 20E in the medium. Incubation in the hormone-free medium
      did not effect accumulation of the AaLAP protein which proceeded at the levels
      comparable to the intact insect. Furthermore, the effect of 10(-5) M 20E on the
      AaLAP accumulation was reversible. These experiments support the hypothesis of
      the 20E-mediated repression of lysosomal protease mRNAs at the translational
      level in the regulation of vitellogenic and postvitellogenic events in the
      mosquito fat body. Analysis of the 5' and 3' -end untranslated regions (UTR) of
      AaLAP mRNA form secondary structures suggest that they may also contribute to
      mRNA stability and 20E-mediated translational inhibition.

PMID- 11222939
TI  - Developmental profile, isolation, and biochemical characterization of a novel
      lipoglycoheme-carrier protein from the American dog tick, Dermacentor variabilis
      (Acari: Ixodidae) and observations on a similar protein in the soft tick,
      Ornithodoros parkeri (Acari: Argasidae).
AB  - A novel lipoglycoheme-carrier protein (CP) in the American dog tick, Dermacentor
      variabilis (Say) has been purified and characterized. CP was purified by native
      PAGE from partially fed virgin females. CP has a density of 1.25 g/ml with a
      molecular weight of 200 K by native-PAGE and 340 K by gel filtration
      chromatography. CP is comprised of two majour subunits, 98 K and 92 K in
      molecular weight by SDS-PAGE. Separate amino acid composition of the two subunits
      indicated high contents of As(x), Gl(x) and leucine. However, the N-terminal
      amino acid sequence of the two subunits was only 13% identical. The lower
      molecular weight subunit showed 61% identity to artemocyanin (biliprotein) in
      fairy shrimps, 46% identity to minor vitellogenin in chickens and 13% identity to
      vitellin of the black-legged tick. No similarity match was found for the other
      subunit. CP is a lipoglycoheme-protein as indicated by selective staining of
      native-PAGE gel for lipids, carbohydrates and heme. Lipid analysis by thin layer
      chromatography revealed the presence of cholesterol, phospholipids,
      monoacylglycerides, triacylglycerides and free fatty acids. Heme associated with
      purified CP demonstrated a lambda(max) of 397.5 nm while the lambda(max) of crude
      hemolymph plasma was 402.5 nm. The presence of CP in whole body homogenates of
      eggs, unfed and fed larvae and fed nymphs as well as in the plasma of unfed and
      fed adults including vitellogenic females was demonstrated by native-PAGE.
      Although a protein of analogous size was not found in the soft tick, Ornithodoros
      parkeri Cooley, a high molecular weight protein (500 K) is the predominant plasma
      protein in both unfed and fed male and female adults of that species as
      determined by native-PAGE. Also, CP appears to function as a biliprotein which
      sequesters heme.

PMID- 11222938
TI  - Biosynthesis and subcellular localization of a lepidopteran insect alpha 1,2
      mannosidase.
AB  - Like lower and higher eucaryotes, insects have alpha 1,2-mannosidases which
      function in the processing of N-glycans. We previously cloned and characterized
      an insect alpha 1,2-mannosidase cDNA and demonstrated that it encodes a member of
      a family of N-glycan processing alpha 1,2-mannosidases (Kawar, Z., Herscovics,
      A., Jarvis, D.L., 1997. Isolation and characterisation of an alpha 1,2
      mannosidase cDNA from the lepidopteran insect cell line Sf9. Glycobiology 7, 433
      443). These enzymes have similar protein sequences, require calcium for their
      activities, and are sensitive to 1-deoxymannojirimycin, but can have different
      substrate specificities and intracellular distributions. We recently determined
      the substrate specificity of the insect alpha 1,2-mannosidase, SfManI (Kawar, Z.,
      Romero, P., Herscovics, A., Jarvis, D.L., 2000. N-glycan processing by a
      lepidopteran insect and 1,2-mannosidase. Glycobiology 10, 347-355). Now, we have
      examined the biosynthesis and subcellular localization of SfManI. We found that
      SfManI is partially N-glycosylated and that N-glycosylation is dramatically
      enhanced if the wild type sequon is changed to one that is highly utilized in a
      mammalian system. We also found that an SfManI-GFP fusion protein had a punctate
      cytoplasmic distribution in insect cells. Colocalization studies indicated that
      this fusion protein is localized in the Golgi apparatus, not in the endoplasmic
      reticulum or lysosomes. Finally, N-glycosylation had no influence over the
      substrate specificity or subcellular localization of SfManI.

PMID- 11222940
TI  - Glutathione S-transferase in the defence against pyrethroids in insects.
AB  - The correlation between the natural levels of GST and the tolerance to the
      insecticide decamethrin (dMT), as well as the interaction between the molecules
      of affinity purified enzyme and the insecticide were investigated in order to
      collect further information on the obscure role of the Glutathione S-transferase
      system (GST) as a mechanism of defence against pyrethroids. The studies were
      carried out, comparatively, on the larvae and pupae developmental stages of the
      coleopteran Tenebrio molitor, which exhibit varying natural levels of GST
      activity. No stage dependent susceptibility of the insect against pyrethroid
      insecticides was found during the first 24 h, however 48 h after treatment, the
      KD50 dose increased significantly due to the recovery of some individuals from
      the larvae stage. Simultaneous injection of decamethrin with compounds which
      inhibit GST activity in vitro, resulted in an increased tolerance, which was more
      pronounced in the pupae stage. Inhibition studies combined with competitive
      fluorescence spectroscopy and high pressure liquid chromatography (HPLC) showed
      that the insecticide binds probably to the active site of the enzyme inhibiting
      its activity towards CDNB in a competitive manner, but is not conjugated with
      GSH. According to this, GST offers a passive protection towards pyrethroid
      insecticides by binding to their molecule in a sequestering mechanism.

PMID- 11222941
TI  - Ecdysteroid-inducible genes in the programmed cell death during insect
      metamorphosis.
AB  - The anterior silk gland of the silkworm, Bombyx mori, undergoes programmed cell
      death (PCD) during pupal metamorphosis and PCD is triggered by 20-hydroxyecdysone
      (20E) in vitro. In order to identify the genes responsible for the PCD, we
      subtracted cDNAs prepared from the anterior silk glands incubated in the presence
      or absence of 20E in vitro. After a series of screenings by dot blot
      hybridization, DNA sequencing and reverse transcription polymerase chain reaction
      (RT-PCR), we obtained seven novel genes that were activated by 20E in vitro.
      Nucleotide sequence analysis indicated that two cDNAs (EN78 and EC08) did not
      have any obvious region to encode proteins, while five genes, designated EC74,
      EN86, EN03, EN10 and EN16, encoded proteins that are similar to inorganic
      phosphate cotransporter, TIA-1-like protein, chitinase-related protein,
      translation-initiation-factor subunit and annexin, respectively. Expression
      profiles of the genes after 20E stimulation indicated that four genes could be
      classified as early genes, while two are delayed early genes. The genes
      identified may provide insight into the PCD induced by a steroid hormone.

PMID- 11222942
TI  - Phenolamine-dependent adenylyl cyclase activation in Drosophila Schneider 2
      cells.
AB  - Drosophila Schneider 2 (S2) cells are often employed as host cells for non-lytic,
      stable expression and functional characterization of mammalian and insect G
      protein-coupled receptors (GPCRs), such as biogenic amine receptors. In order to
      avoid cross-reactions, it is extremely important to know which endogenous
      receptors are already present in the non-transfected S2 cells. Therefore, we
      analyzed cellular levels of cyclic AMP and Ca2+, important second messengers for
      intracellular signal transduction via GPCRs, in response to a variety of
      naturally occurring biogenic amines, such as octopamine, tyramine, serotonin,
      histamine, dopamine and melatonin. None of these amines (up to 0.1 mM) was able
      to reduce forskolin-stimulated cyclic AMP production in S2 cells. Furthermore, no
      agonist-induced calcium responses were observed. Nevertheless, the phenolamines
      octopamine (OA) and tyramine (TA) induced a dose-dependent increase of cyclic
      adenosine monophosphate (AMP) production in S2 cells, while serotonin, histamine,
      dopamine and melatonin (up to 0.1 mM) did not. The pharmacology of this response
      was similar to that of the octopamine-2 (OA2) receptor type. In addition, this
      paper provides evidence for the presence of an endogenous mRNA encoding an
      octopamine receptor type in these cells, which is identical or very similar to
      OAMB. This receptor was previously shown to be positively coupled to adenylyl
      cyclase.

PMID- 11222943
TI  - Partial purification of a novel insect antidiuretic factor from the Colorado
      potato beetle, Leptinotarsa decemlineata (Say) (Coleoptera: Chrysomelidae), which
      acts on Malpighian tubules.
AB  - In this study, we report for the first time the presence of an antidiuretic
      factor in the head of the Colorado potato beetle (Leptinotarsa decemlineata
      (Say)) which acts directly on Malpighian tubules. Biologically active fractions
      were isolated from the head and separated using molecular weight filtration and
      high-performance liquid chromatography (HPLC). The resulting fractions were
      tested for their antidiuretic activity on single isolated Malpighian tubules.
      Antidiuretic activity was found in the 25% acetonitrile Sep-Pak fraction and the
      Cn-2 (3000-10,000 MW) and Cn-3 (<3000 MW) fractions, suggesting that the
      antidiuretic factor was probably a peptide of 25 to 50 amino acids. The
      antidiuretic factor was very potent, since after five successive fractionations
      on two different HPLC columns, a high level of inhibition (63%) of fluid
      secretion by Malpighian tubules could be observed at low dose (0.14 head
      equivalent/microl). The antidiuretic factor isolated from the head of the
      Colorado potato beetle was not affected by repeated freezing and thawing but was
      sensitive to heat. The differences observed between the Colorado potato beetle
      antidiuretic factor and other insect diuretic and antidiuretic factors may
      indicate the possibility of a novel family of water regulation hormones in
      insects.

PMID- 11222944
TI  - Developmental profile of the changes in the prothoracicotropic hormone titer in
      hemolymph of the silkworm Bombyx mori: correlation with ecdysteroid secretion.
AB  - A very sensitive time-resolved fluoroimmunoassay for the prothoracicotropic
      hormone (PTTH) of the silkworm Bombyx mori has been established. The lower limit
      of detection in this assay was 0.1 pg. With this assay method, the amounts of
      PTTH in the central nervous system and hemolymph were quantified. PTTH was
      detected only in the brain within the central nervous system, and, in the fifth
      instar, its content in the brain increased gradually with larval growth and
      decreased rapidly after the beginning of wandering. A substantial amount of PTTH
      was also found in the retrocerebral complex of day-3 fifth instar larvae,
      accounting for 28% of total PTTH. The PTTH titer in hemolymph changed
      dramatically during Bombyx development, with a small peak in the middle of the
      fourth instar, medium-sized peaks at the wandering and prepupal stages in the
      fifth instar, and a large prolonged peak during early pupal-adult development.
      The changes were overall closely correlated with those in hemolymph ecdysteroid
      titer. However, some unexpected aspects of PTTH dynamics in hemolymph have also
      been disclosed. Based on these observations, the significance of PTTH secretion
      in the control of insect development is discussed.

PMID- 11222945
TI  - Heme biosynthesis and oogenesis in the blood-sucking bug, Rhodnius prolixus.
AB  - We have previously shown that the pathway of porphyrin synthesis operates in the
      blood feeding triatomine bug Rhodnius prolixus but not in the cattle tick
      Boophilus microplus. In the present paper we studied the correlation between heme
      synthesis and egg development in Rhodnius. There is a sharp increase heme
      biosynthetic capability in the fat body (160%) and in the ovaries (360%) in
      response to a blood meal, as evaluated from the activity of the enzyme delta
      aminolevulinate dehydratase (EC 4.2.1.24). The in vivo inhibition of ALA-D by
      succinyl acetone results in a dose dependent decrease of oviposition. Oviposition
      is recovered when porphobilinogen, the product of the impaired reaction, is added
      to the succinyl acetone enriched blood. Taken together, these results show that
      heme biosynthesis is a fundamental event to vitellogenic females. The demand for
      heme in this metabolic juncture cannot be supplied by the heme eventually
      absorbed during blood digestion and associated with Rhodnius heme binding protein
      (RHBP), which is then incorporated into growing oocytes. Inhibition of heme
      biosynthesis results in lower levels of RHBP in the hemolymph, suggesting that
      the synthesis of this protein is controlled by heme availability.

PMID- 11222946
TI  - Variations in chemical mimicry by the ectoparasitic mite Varroa jacobsoni
      according to the developmental stage of the host honey-bee Apis mellifera.
AB  - The ectoparasitic mite Varroa jacobsoni poses a major threat to the survival of
      European honey-bee populations. Development of effective control methods is
      therefore much needed. Study of interspecific chemical communication between the
      parasite and host is a particularly promising avenue of research. Previous study
      has shown that the cuticular hydrocarbons of the parasite mite Varroa jacobsoni
      are qualitatively identical to those of its honey-bee host Apis mellifera (Nation
      J.L., Sanford M.T., Milne K., 1992. Cuticular hydrocarbons from Varroa jacobsoni.
      Experimental and Applied Acarology 16, 331-344). The purpose of the present study
      was to compare the cuticular hydrocarbon patterns of the two species at different
      stages of bee development. Cuticular components were identified by gas
      chromatography/mass spectrometry. The proportion of each component was calculated
      at three stages of bee development (larvae, pupa, emerging bee). The degree of
      chemical mimicry between the parasite and host was evaluated by multivariate
      analyses using the resulting proportions for each category of individuals. There
      were four main findings. The first was that the proportions of some components
      are different at the larval, pupal and imago stage of bee development. Second,
      Varroa profiles vary depending on the developmental stage of the host. Third, the
      cuticular profile of adult mites is more similar to that of the stage of the host
      than that of later and/or earlier stages except for parasites collected from
      emerging adult bees. Fourth, the degree of mimicry by Varroa is greater during
      larval and pupal stages than during the emerging adult bee stages. The role of
      chemical mimicry - although it is not perfect - in enabling parasites to infest
      bee colonies by the parasite is discussed.

PMID- 11222947
TI  - Antagonistic effects of hypertrehalosemic neuropeptide on the activities of 6
      phosphofructo-1-kinase and fructose-1,6-bisphosphatase in cockroach fat body.
AB  - Hypertrehalosemic neuropeptides from the corpora cardiaca such as the decapeptide
      Bld HrTH bring about a profound switch in the metabolic activity of cockroach fat
      body during which production of the blood sugar trehalose is stimulated while the
      catabolism of carbohydrate (glycolysis) is inhibited. The mechanisms of the
      metabolic switch are not fully understood. Incubation of isolated fat body from
      the cockroach Blaptica dubia with 10(-8) M Bld HrTH, for 10-60 min, stimulated
      glycogen breakdown and increased the content of the substrates of both the
      glycolytic enzyme 6-phosphofructo-1-kinase (PFK, EC 2.7.1.11) and the
      gluconeogenic enzyme fructose-1,6-bisphosphatase (FBPase, EC 3.1.3.11) in the
      tissue. The glycolytic signal fructose 2,6-bisphosphate was markedly decreased in
      fat body on incubation with Bld HrTH. The content of ATP was slightly reduced,
      while the contents of ADP and AMP were increased after incubation with the
      hormone. Fructose 2,6-bisphosphate is a potent activator of PFK and a strong
      inhibitor of FBPase purified from fat body. The activity of PFK was decreased by
      about 90% when the hormone-dependent changes in effectors and substrates in fat
      body were simulated in vitro. FBPase, in contrast, was activated about 25-fold
      under these conditions, suggesting the hormone to stimulate gluconeogenesis in
      fat body. The data support the view that fructose 2,6-bisphosphate is a pivotal
      intracellular messenger in the hormone-induced metabolic switch from carbohydrate
      degradation to trehalose production in cockroach fat body.

PMID- 11222948
TI  - Daily variations of antioxidant enzyme and luciferase activities in the
      luminescent click-beetle Pyrearinus termitilluminans: cooperation against oxygen
      toxicity.
AB  - Several lines of investigation have suggested an interplay between
      bioluminescence (BL) and oxyradical metabolism, mainly in bacteria and beetles.
      Although not yet confirmed, luminescent beetles seem to be challenged daily by
      oxidative conditions imposed by higher oxygen absorption necessary to enhance
      light emission for courtship (adult lampyrids and elaterids) and prey attraction
      (e.g. Pyrearinus termitilluminans larvae). This work reports the activities of
      luciferase, superoxide dismutase (SOD), catalase and dehydroascorbate reductase
      (DHAR) and total glutathione content at different times of the day in the bright
      prothorax and dim abdomen of larval Pyrearinus termitilluminans (Coleoptera:
      Elateridae), investigating a possible adjuvant role for luciferase in oxygen
      detoxification. Luciferase activity in the prothorax was shown to peak at 7 p.m.,
      which is the time when P. termitilluminans larvae light up for prey attraction.
      In their habitat, P. termitilluminans larvae emit light until 8.30 p.m. However,
      at 8 p.m., prothorax luciferase activity achieved basal levels and total
      glutathione content declined to the daily lowest value, possibly resulting from
      hyperoxidative conditions during this time. Significant increases in the
      activities of total SOD (28%) and catalase (37%) were observed in the prothorax
      at 9 p.m., which should minimize the extent of damage from this potentially
      hazardous period. Prothorax total SOD (42% higher than daily average) and abdomen
      CuZnSOD (41%) and catalase (95%) activities showed extra peaks at 7-10 a.m., and
      abdomen DHAR activity was maximal (37%) earlier (4-7 a.m.). These morning
      increases in antioxidant enzyme activities may be associated with biological
      events other than bioluminescence, e.g. intense physical activity for digging
      tunnels and/or digestion of captured preys. These data suggest that oxyradical
      pathway and bioluminescence are coordinated, especially in the prothorax, to
      minimize the oxidative stress imposed by higher irrigation of the photocytes with
      O(2) when P. termitilluminans larvae emit light.

PMID- 11222949
TI  - Thiafatty acids as tracers to investigate biosynthetic pathways of lepidopteran
      sex pheromones.
AB  - In order to investigate the potential utility of thiafatty acids as tracers for
      biosynthetic studies of moth sex pheromones, a series of thiatetradecanoic acids,
      namely 8-, 9-, 10-, 11-, 12- and 13-thiatetradecanoic, were prepared and their
      metabolism was investigated in pheromone glands of Spodoptera littoralis.
      Analysis by gas chromatography coupled to mass spectrometry of extracts from
      pheromone glands treated with the above acids showed that only 8
      thiatetradecanoic acid and 13-thiatetradecanoic acid were metabolized by
      desaturation and were incorporated into the sex pheromone biosynthetic pathway.
      13-Thiatetradecanoic acid was converted into (E)- and (Z)-13-thiatetradec-11
      enoic acids, (Z,E)-13-thiatetradeca-9,11-dienoic acid, 11-thiadodecanoic acid,
      (E)- and (Z)-11-thiadodec-9-enoic acids and 15-thiahexadecanoic acid. 8
      Thiatetradecanoic acid gave rise to two monoenoic thiafatty acids and two dienoic
      thiafatty acids, which were assigned to (Z)- and (E)-8-thiatetradec-11-enoic
      acids, (Z,E)-8-thiatetradeca-9,11-dienoic acid and (E,E)-8-thiatetradeca-10,12
      dienoic acid. The other thiafatty acids tested, 9-, 10-, 11- and 12
      thiatetradecanoic acids, were not metabolized by desaturation, although the
      corresponding products of beta-oxidation and chain elongation were detected. The
      occurrence of sulfoxides was not detected in this case, in disagreement with
      results on the metabolism of some thiaacids previously reported by other authors
      in yeast, Saccharomyces cerevisiae.

PMID- 11222950
TI  - The 30kP protease A responsible for 30-kDa yolk protein degradation of the
      silkworm, Bombyx mori: cDNA structure, developmental change and regulation by
      feeding.
AB  - We have cloned and sequenced the cDNA encoding the major component (43-kDa
      peptide) of 30kP protease A which selectively hydrolyzes 30-kDa yolk proteins of
      the silkworm, Bombix mori. The deduced amino acid sequence consisted of 318 amino
      acids and shared sequences conserved in many serine proteases. Northern blot
      analysis using the cDNA as probe revealed that 43-kDa peptide mRNA began to rise
      at the last phase of embryogenesis and reached a maximum level at larval
      hatching. This level was maintained with some fluctuations throughout post
      embryonic development. The concentration of 43-kDa peptide increased greatly
      toward larval hatching coinciding with the changing pattern of mRNA. When larvae
      were fed, the peptide concentration abruptly decreased and remained near zero
      throughout post-embryonic development. The decrease in peptide concentration did
      not occur, however, when the hatched larvae were starved. Thus, the nutritional
      shift from endogenous yolk to exogenous food plays a key role in 30kP protease A
      elimination from neonate larvae.

PMID- 11222951
TI  - Preliminary characterisation of digestive proteases of the green mirid,
      Creontiades dilutus (Hemiptera: Miridae).
AB  - Protease activities in the secreted saliva, salivary glands and midgut of the
      green mirid, Creontiades dilutus, were investigated. The saliva and salivary
      glands had more protease activity than the midgut, but no differences in protease
      activity levels were detected between male and female mirids, adult mirids and
      third instar nymphs, or between fed and starved mirids. In the salivary glands,
      chymotrypsin-like serine proteases predominated, as characterised by inhibitor
      specificity, basic pH optima, and hydrolysis of N-benzoyl-L-tyrosine p
      nitroanilide and N-succinyl-ala-ala-pro-leu p-nitroanilide. The pH optimum of
      midgut extracts was acidic (pH 4), implying that acidic proteases predominate.
      However, protease activity was inhibited substantially by both aprotinin and E
      64, suggesting the presence of both serine and cysteine proteases in the midgut
      of the green mirid.

PMID- 11222952
TI  - 3-Hydroxy-3-methylglutaryl coenzyme A synthase-1 of Blattella germanica has
      structural and functional features of an active retrogene.
AB  - Blattella germanica has two cytosolic 3-hydroxy-3-methylglutaryl coenzyme A (HMG
      CoA) synthase genes, HMG-CoA synthase-1 and -2. HMG-CoA synthase-1 gene shows
      several features of processed genes (retroposons): it contains no introns but has
      a short direct-repeat sequence (ATTATTATT) at both ends. An atypical feature is
      the presence at both ends of the gene of short inverse repeats flanked by direct
      repeats. There is neither a TATA box nor a CAAT box in the 5' region. Comparative
      analysis with other species suggests that the HMG-CoA synthase-1 gene derives
      from HMG-CoA synthase-2. Cultured embryonic B. germanica UM-BGE-1 cells express
      HMG-CoA synthase-1 but not HMG-CoA synthase-2, suggesting that the intron-less
      gene is functional. In addition, it can complement MEV-1 cell line, which is
      auxotrophic for mevalonate. We show that compactin and mevalonate do not
      significantly affect the mRNA levels of HMG-CoA synthase-1 in UM-BGE-1 cells.
      Compactin induces a 6.7-fold increase in HMG-CoA reductase activity, which is
      restored to normal levels by mevalonate. HMG-CoA synthase activity is not
      modified by either of these effectors, suggesting that the mevalonate pathway in
      this insect cell line is regulated by post-transcriptional mechanisms affecting
      HMG-CoA reductase but not HMG-CoA synthase.

PMID- 11222953
TI  - Prostaglandin biosynthesis by fat body from true armyworms, Pseudaletia
      unipuncta.
AB  - We describe prostaglandin (PG) biosynthesis by microsomal-enriched fractions of
      fat body prepared from true armyworms, Pseudaletia unipuncta. PG biosynthesis was
      sensitive to experimental conditions, including incubation time, temperature, pH,
      substrate and protein concentration. Optimal PG biosynthesis conditions included
      1 mg of microsomal-enriched protein, incubated at 28 degrees C for 7.5 min at pH
      8. These preparations yielded four major PGs: PGA(2), PGE(2), PGD(2) and
      PGF(2alpha). PGA(2) and PGE(2) were the predominant eicosanoids produced under
      these conditions. Two non-steroidal anti-inflammatory drugs, indomethacin and
      naproxen, effectively inhibited PG biosynthesis. Unlike other invertebrate PG
      biosynthetic systems studied so far, the true armyworm system appeared to be
      independent of the usual exogenous co-factors required by mammalian and other
      invertebrate systems. These findings are discussed with respect to PG
      biosynthesis in other invertebrate and vertebrate systems.

PMID- 11222954
TI  - Matrix proteins from insect pliable cuticles: are they flexible and easily
      deformed?
AB  - Proteins from pliable cuticle of locusts, Schistocerca gregaria, and silk moth
      larvae, Hyalophora cecropia, were studied in solution by means of a fluorescent
      probe, 8-anilinonaphthalene-1-sulphonic acid (ANS), which is much more
      fluorescent in non-polar media than in polar media. An intense ANS-fluorescence
      was observed in the presence of the cuticular proteins at pH-values close to
      their acidic isoelectric points, and the fluorescence decreased markedly when pH
      was increased to neutrality or when small amounts of denaturants were added.
      Aggregation and eventual precipitation of both H. cecropia and locust proteins
      were obtained by addition of neutral salts, and the aggregation was accompanied
      by an increased ANS-fluorescence intensity. A decreased ANS-fluorescence was
      observed at salt concentrations too low to cause visible aggregation of the H.
      cecropia proteins, probably due to weakened electrostatic interactions between
      chain segments, but such a decrease was not observed for the locust proteins. The
      changes in intensity of ANS-fluorescence induced by addition of small amounts of
      denaturants or salts to solutions of the proteins indicate that more hydrophobic
      residues are exposed to the solvent, when either hydrophobic interactions or
      electrostatic attractions between chain segments are weakened. The result is a
      less compact protein structure, where fewer and smaller hydrophobic clusters are
      available for protecting ANS-molecules from the quenching effects of water. The
      effects of denaturants on ANS-fluorescence in the presence of the cuticular
      proteins are different from those observed for globular proteins, such as hen egg
      albumen, and the differences can be explained by the suggestion that the
      cuticular proteins do not have a precisely folded and densely packed hydrophobic
      core comparable to that present in native globular proteins, and that accordingly
      they do not undergo a process of denaturation corresponding to that of globular
      proteins. The behaviour of the cuticular proteins resembles that described for
      unordered, randomly coiled, thermally agitated polymer chains, whose hydrodynamic
      volumes depend upon the composition of the medium. It is proposed that the major
      part of the peptide chains of the cuticular proteins are in an unordered, random
      structure both when the proteins are in solution and when present in the intact
      cuticle; probably only the chain regions involved in binding the proteins to
      chitin will have a well-defined spatial organisation.

PMID- 11222955
TI  - Complexity in specificities and expression of Helicoverpa armigera gut
      proteinases explains polyphagous nature of the insect pest.
AB  - Helicoverpa armigera is a devastating pest of cotton and other important crop
      plants all over the world. A detailed biochemical investigation of H. armigera
      gut proteinases is essential for planning effective proteinase inhibitor (PI)
      based strategies to counter the insect infestation. In this study, we report the
      complexity of gut proteinase composition of H. armigera fed on four different
      host plants, viz. chickpea, pigeonpea, cotton and okra, and during larval
      development. H. armigera fed on chickpea showed more than 2.5- to 3-fold
      proteinase activity than those fed on the other host plants. H. armigera gut
      proteinase composition revealed the predominance of serine proteinase activity;
      however, the larvae fed on pigeonpea revealed the presence of metalloproteases
      and low levels of aspartic and cysteine proteases as well. Gut proteinase
      activity increased during larval development with the highest activity seen in
      the fifth instar larvae which, however, declined sharply in the sixth instar.
      Over 90% of the gut proteinase activity of the fifth instar larvae was of the
      serine proteinase type, however, the second instar larvae showed the presence of
      proteinases of other mechanistic classes like metalloproteases, aspartic and
      cysteine proteases along with serine proteinase activity as evident by inhibition
      studies. Analysis of fecal matter of larvae showed significant increase in
      proteinase activity when fed on an artificial diet with or without non-host PIs
      than larvae fed on a natural diet. The diversity in the proteinase activity
      observed in H. armigera gut and the flexibility in their expression during
      developmental stages and depending upon the diet provides a base for selection of
      proper PIs for insect resistance in transgenic crop plants.

PMID- 11222956
TI  - Triapsin, an unusual activatable serine protease from the saliva of the
      hematophagous vector of Chagas' disease Triatoma infestans (Hemiptera:
      Reduviidae).
AB  - Salivary anticoagulant activities are widely distributed among hematophagous
      arthropods. Most of them are inhibitors of the serine proteases of the
      coagulation cascade. Here we show that the saliva of the exclusively
      hematophagous insect Triatoma infestans, an important vector in the transmission
      of Chagas' disease, contains an uncommon trypsin-like activity, triapsin. This
      novel enzyme was purified and characterized. It is a serine protease that is
      stored as a zymogen in the luminal content of the salivary glands D2. Triapsin is
      activated by trypsin treatment, or when the saliva is ejected during the insect
      bite. The enzyme was purified 300-fold from the released saliva by anion exchange
      chromatography in a HiTrap Q column, followed by chromatography in Phenyl
      Superose, and Superdex HR75. The purified triapsin shows an apparent molecular
      mass of around 40 kDa in non-reduced SDS gels and in sieving chromatography, and
      33 kDa in reduced SDS-gels. Its activity is lost after incubation with
      dithiothreitol indicating that cysteine bridges are essential for activity.
      Triapsin cleaves gelatin and synthetic substrates showing preference for arginine
      at P1 residues. The best p-nitroanilide substrate is isoleucyl-prolyl-arginine.
      It does not cleave bradykinin, angiotensin and other lysine containing
      substrates. The triapsin amidolytic activity against chromogenic substrates is
      similar to plasminogen activators, such as urokinase and tissue plasminogen
      activator. However, it does not activate plasminogen. The fact that triapsin is
      released at the bite in its active form suggests that it has a role in blood
      feeding.

PMID- 11222957
TI  - The biolistic method as a tool for testing the differential activity of putative
      silkmoth chorion gene promoters.
AB  - Bombyx mori unpaired early chorion gene copies 6F6.1,.2 and.3 are exceptions to
      the typical organization and distribution pattern of known early ErA/ErB, middle
      A/B and late HcA/HcB divergently transcribed gene pairs. Contrary to such pairs,
      the boundaries of the 6F6 regulatory sequences are not easily defined; moreover,
      they share common sequence elements with the regulatory sequences of middle and
      late genes. In order to perform a functional study of the tissue and temporal
      specificity of the 6F6 putative promoter region, we decided to apply biolistics.
      In the present work, use of a region from the 6F6.2 5' untranslated sequence,
      spanning nucleotides -138 to the cap site, gave an expected expression pattern of
      a lacZ reporter gene. Temporal specificity was further verified by control
      experiments using the cloned intergenic sequence of the late gene pair HcA/B.12,
      which resulted in lacZ expression in late choriogenic follicles. At present,
      despite the recent successful germinal transgenesis of Bombyx mori, the biolistic
      transient expression system seems to be the most rapid technique to pursue the
      functional study of the promoter region of early chorion genes, including the
      three unconventional early 6F6 genes.

PMID- 11222958
TI  - Aedes aegypti peroxidase gene characterization and developmental expression.
AB  - The functions of insect peroxidases include detoxification, stabilization of
      extracellular matrices, and possible involvement in insect immunity. The current
      study describes the isolation of a peroxidase gene, AePox, and its cDNA from the
      mosquito, Aedes aegypti. AePox codes for a protein that is homologous to various
      heme-peroxidases from vertebrates and invertebrates, with highest identity to
      Drosophila melanogaster peroxidase (62%). Sequence comparison identified several
      functionally and structurally conserved domains in the mosquito peroxidase,
      including a heme environment, a calcium binding site, and five possible disulfide
      bridges. These results imply that AePOX may likely have a similar structure and
      catalytic mechanism as those described for the mammalian myeloperoxidase
      superfamily. Expression studies demonstrate that AePox is transcribed in mosquito
      larvae and pupae, but not in adults, in ovaries, or in early embryos. However,
      AePOX protein is present in all mosquito stages and possibly has a maturation
      process that is similar to that of human myeloperoxidase. Unlike most human
      peroxidases, the AePox gene contains a TATA box and an ecdysone response element
      (EcRE).

PMID- 11222959
TI  - Expression of host S-adenosylmethionine decarboxylase gene and polyamine
      composition in aphid bacteriocytes.
AB  - Differential cDNA display and quantitative RT-PCR revealed that mRNA of host S
      adenosylmethionine decarboxylase (SAMDC) was abundant only in the aphid
      endosymbiotic system well organized in young hosts, suggesting that SAMDC plays
      some important roles in the system. SAMDC is a key enzyme to synthesize
      polyamines that are known to be involved in a large array of biological events
      including protein synthesis, DNA stabilization, DNA replication, and cell
      proliferation. As the first step to investigate roles of polyamines in the
      endosymbiotic system, polyamine composition in bacteriocytes was determined by
      high performance liquid chromatography. As a result, we found that bacteriocytes
      contained virtually an only single polyamine, spermidine. The spermidine content
      of bacteriocytes fluctuated with time in the course of development and aging of
      the host aphid. This is the first report of polyamine assessment in a prokaryote
      eukaryote endocellular symbiotic system, which demonstrated a unique polyamine
      composition.

PMID- 11222960
TI  - A genomic clone for a chitinase gene from the silkworm, Bombyx mori: structural
      organization identifies functional motifs.
AB  - A genomic clone containing the chitinase gene was isolated and characterized from
      the silkworm, Bombyx mori, using the polymerase chain reaction technique directed
      by primers designed from the chitinase cDNA of the insect previously cloned
      [Insect Biochem. Molec. Biol. 28 (1998) 163]. Results from nucleotide sequence
      analysis of the gene and its PCR amplification suggest that the B. mori genome
      probably has only one copy of chitinase gene. The gene is organized into 10
      coding regions, exons, interrupted by noncoding regions, introns. The motifs
      encoded and exon organization of the gene are almost identical to the related
      gene from Manduca sexta. The results suggest that the domain organization of
      chitinase genes may be conserved among insect cuticular chitinase genes and that
      they are more complex than their counterparts in plants. The possibilities of
      intron splicing from the primary transcripts are also discussed.

PMID- 11222961
TI  - Separation of spikes from background by independent component analysis with
      dipole modeling and comparison to intracranial recording.
AB  - OBJECTIVE: Epileptiform discharges can be objectively separated from the EEG
      background by independent component analysis (ICA) into the discharge's waveform
      and its spatial distribution. The correspondence between ICA components,
      including epileptiform transients extracted from the scalp EEG and intracranial
      epileptic fields, was investigated. METHODS: In 11 spike patterns from 8
      patients, the scalp EEG data were decomposed by ICA. The corresponding averaged
      intracranial data were compared with the extracted epileptic components regarding
      the number of source patterns and source locations estimated from ICA maps.
      RESULTS: Clear epileptic components could be separated in 10/11 spike patterns.
      The number of epileptic components was identical to the number of intracranial
      field peaks in 7 spike patterns with simple intracranial fields, and was less in
      the remaining 3 patterns with complex intracranial peaks. The distance between
      the contact of the maximal intracranial field and the dipole location estimated
      by the single dipole model for the clearest epileptic component ranged from 4.7
      to 31.9 mm. CONCLUSIONS: The number of epileptic ICA components largely matched
      the number of intracranial field patterns, and the dipole location estimated for
      the map of the clearest epileptic component was generally correct. This
      establishes the validity of epileptic components extracted by ICA from the scalp
      background.

PMID- 11222962
TI  - Dipole modeling of scalp electroencephalogram epileptic discharges: correlation
      with intracerebral fields.
AB  - OBJECTIVE: In order to evaluate the feasibility of modeling seizures and the
      reliability of dipole models, we compared source localizations of scalp seizures
      with the distribution of simultaneous intracerebral electroencephalogram (SEEG).
      METHODS: In a first session, only scalp electroencephalogram (EEG) was recorded
      from 15 patients. We averaged the first detectable ictal activity in two
      consecutive segments of stable topography and morphology. Spatio-temporal dipole
      sources were estimated for each segment and projected on 3D-magnetic resonance
      images. In a second session, SEEG was recorded simultaneously with control scalp
      electrodes, allowing the identification of ictal patterns similar to those
      submitted to dipole modeling. RESULTS: Ictal discharges could be analyzed in only
      6 of 15 patients. In the remaining 9, scalp discharges were undetectable or non
      reproducible in 6, and solutions were unstable despite an apparently stable
      discharge in 3. In the 6 patients successfully modeled, dipoles were found in
      regions where SEEG discharges were present. However, when intracerebral
      discharges were very focal, there was no corresponding scalp activity. When
      intracerebral signals were maximal in the mesial temporal regions at the seizure
      onset, only lateral neocortical dipoles were found. When discharges reached the
      frontal lobes, we could identify lateral and mesial frontal sources. CONCLUSIONS:
      In most seizures, it was not possible to obtain satisfactory dipole models,
      probably a reflection of the high noise level or widespread generators. When
      modeling was possible, our results suggested that mesial temporal seizure
      discharges did not contribute to scalp EEG activity. This activity appears to
      reflect signals synchronized and distributed over the lateral temporal or frontal
      neocortex, as well as signals generated in mesial frontal areas.

PMID- 11222963
TI  - Potentials recorded at the scalp by stimulation near the human subthalamic
      nucleus.
AB  - OBJECTIVE: To record the potentials evoked at the scalp by stimulation through
      electrodes targeted at the human subthalamic nucleus (STN) and to determine
      whether the responsible pathways continue to be excited or become blocked with
      high frequency stimulation. METHODS: We recorded the potentials evoked at the
      scalp in response to single and multiple stimuli delivered through STN contacts
      in 6 patients with Parkinson's disease. RESULTS: On 9/11 sides tested, single
      stimuli elicited a negative potential with latency of approximately 3 ms which
      was largest over the frontal region. Its short chronaxie (50 micros) and
      refractory period imply that it arose from the activation of low threshold neural
      elements, possibly myelinated axons. This potential could follow at 100 Hz. This
      early potential was sometimes followed by later negative potentials at
      approximately 5 ms (6/11 sides) and approximately 8 ms (8/11 sides). The
      responsible neural elements had the same short chronaxie. These potentials were
      augmented by paired stimuli at separations of 2-7 ms and by trains of stimuli at
      200 Hz. CONCLUSIONS: Trains of stimuli delivered to the STN may excite low
      threshold neural elements which can transmit impulses at frequencies >100 Hz
      without blocking and which may produce postsynaptic facilitation at the cortex.

PMID- 11222965
TI  - Neurophysiological mechanisms underlying motor evoked potentials in anesthetized
      humans. Part 2. Relationship between epidurally and muscle recorded MEPs in man.
AB  - OBJECTIVE AND METHODS: Direct (D) and transynaptic, (i.e. indirect) (I)
      corticospinal tract (CT) discharges were simultaneously recorded epidurally with
      muscle motor evoked potentials (MEPs) in patients under different levels of
      anesthesia. The effects of the one, two or more equal electrical stimuli, applied
      transcranially or directly to the motor cortex, were studied at different
      interstimulus intervals (ISIs) to determine the optimal conditions for eliciting
      I and MEP responses. RESULTS AND CONCLUSION: At anesthetic levels permiting large
      D and I responses to single stimuli, optimal D and I wave facilitation and MEPs
      occurred with two stimuli at ISIs greater than 4 ms (e.g. at 5.9 and 8 ms). When
      single electrical stimuli elicit only a D response, optimal MEP responses are
      determined by the number of stimuli and the recovery of CT fibers excitability
      (e.g. at an ISI of 4 ms).

PMID- 11222966
TI  - Crossed effects of muscle vibration on motor-evoked potentials.
AB  - OBJECTIVES: Muscle vibration (MV) to a forearm muscle augments motor-evoked
      potentials (MEPs) following transcranial magnetic stimulation (TMS) and the
      underlying mechanism involves cortical structures. Although MV-induced cortical
      activation is bilateral, the effects of MV on MEPs in contralateral muscles have
      not been investigated. METHODS: Low-amplitude MV (80 Hz, amplitude 0.5 mm,
      duration 4 s), subthreshold for the tonic vibration reflex, was applied to the
      right extensor carpi radialis muscle (ECR). MEPs were elicited (0.5, 3 and 5 s
      after MV onset) in the left and right ECR and flexor carpi radialis muscle (FCR)
      by TMS (120% of threshold at rest) to the left and right hemisphere,
      respectively. RESULTS: During MV of right ECR the left ECR revealed a slight non
      significant augmentation of MEPs. In contrast, the left FCR showed a gradual
      depression of MEPs with ongoing MV and at 3 s the reduction of MEPs was
      significant. The time course of MEP changes in left FCR correlated with the
      facilitation of the vibrated right ECR. Post-vibration MEPs at 1 s after the
      offset of MV were still significantly decreased. CONCLUSIONS: The study
      demonstrates crossed effects of MV on motor cortex excitability, suggesting
      transcallosal MEP modulation.

PMID- 11222964
TI  - Neurophysiological mechanisms underlying motor evoked potentials in anesthetized
      humans. Part 1. Recovery time of corticospinal tract direct waves elicited by
      pairs of transcranial electrical stimuli.
AB  - Direct (D) corticospinal tract discharges were recorded epidurally in patients at
      anesthetic depths suppressing indirect (I) activity and were elicited by two
      equal transcranial electrical stimuli. The recovery of amplitude of the second D
      wave (D2) was a function of the interstimulus interval (ISI) and the stimulus
      duration. For example, with a 100 micros pulse, there was no response at an ISI
      of 1.1 ms, but partial recovery occurred with a 500 micros pulse. This indicates
      a relative refractory component at this ISI. Both D2 amplitude and conduction
      time recovered completely using a 4 ms ISI, with evidence of increased amplitude
      and reduced conduction time (supernormality) at longer ISIs. These findings are
      relevant in explaining high frequency D and I discharges and facilitation of
      motor responses by two transcranial magnetic pulses. Furthermore, these data help
      to understand why an ISI of 4 ms would be optimal in eliciting limb muscle
      responses when a short train of transcranial stimuli elicits only D waves in
      anesthetized patients (Deletis et al., Clin Neurophysiol 112 (2001) 445).

PMID- 11222967
TI  - Terminal latency index and modified F ratio in distinction of chronic
      demyelinating neuropathies.
AB  - OBJECTIVE: To evaluate indexes calculated from standard electrophysiological data
      in differentiating chronic demyelinating polyneuropathy (CDP). METHODS: Nerve
      conduction study of upper limbs was investigated in 19 chronic inflammatory
      demyelinating polyneuropathy (CIDP) patients, 25 anti-myelin-associated
      glycoprotein/sulfated glucuronyl paragloboside antibodies (MAG/SGPG) CDP
      patients, 13 Charcot-Marie-Tooth disease type 1A (CMT1A) patients and 22
      controls. Terminal latency index (TLI) was used to compare the wrist-to-thenar
      muscle segment with the elbow-to-wrist conduction velocity. Modified F ratio
      (MFR) was used to compare the spinal cord-to-elbow segment latency with that of
      the wrist-to-thenar muscle segment. RESULTS: Compared with controls, TLI was
      decreased in 21 anti-MAG/SGPG CDP patients while MFR was either decreased or was
      normal. In 16 CIDP patients, MFR was increased while TLI was either normal or
      increased. In CMT1A both TLI and MFR were in normal ranges. The sensitivity of
      MFR as a supportive finding in CIDP was found to be 84% and its specificity 89%.
      The sensitivity of TLI as a mean of diagnosis of anti-MAG/SGPG CDP was found to
      be 93% and its specificity 90%. CONCLUSIONS: The results of TLI and MFR
      facilitates distinction between different types of CDP. In CIDP, MFR was
      significantly higher and TLI showed no change; in the anti-MAG/SGPG CDP, TLI and
      MFR were significantly lower; in CMT1A, TLI and MFR showed no change in
      comparison with the controls.

PMID- 11222968
TI  - Simulation of the normal concentric needle electromyogram by using a muscle
      model.
AB  - OBJECTIVES: To study the correlation between anatomical parameters and EMG
      signals by means of simulations. METHODS: A mathematical model of the electrical
      activity from muscle fibres and motor units has been developed. The electrical
      fields around the muscle fibres are simulated using a line source model. The
      model permits the simulation of single muscle fibre action potentials obtained by
      SFEMG, concentric and Macro EMG electrodes. By using appropriate anatomical
      parameters EMG recordings with these electrodes can be simulated. The model is
      flexible and permits a number of anatomical parameters to be changed such as;
      number of muscle fibres in a motor unit, fibre diameter distribution, and motor
      end-plate geometry. Some physiological parameters can be optionally varied;
      firing rate, threshold for recruitment, jitter. RESULTS: In this study,
      simulations of CNEMG are performed and the influence of a number of parameters on
      the CNEMG signal is studied. It is shown that the model produces motor unit
      potentials reasonably well resembling those from live recordings. More important
      is however the relative change in MUP parameters when certain conditions are
      changed; number of muscle fibres in a motor unit, recording position, muscle
      fibre diameters and some special effects of the recording conditions.
      CONCLUSIONS: The simulated muscle and corresponding EMG recording can be used
      both as a research tool and for teaching.

PMID- 11222969
TI  - Pudendal nerve terminal motor latency: age effects and technical considerations.
AB  - OBJECTIVES: The measurement of the pudendal nerve terminal motor latency (PNTML)
      is used to assess anal sphincter innervation. In healthy subjects, we studied the
      influence of age on PNTML and the advantage of a new intra-rectal stimulator.
      METHODS: PNTML was determined in a first series of 40 normal subjects, aged 21-75
      years, using a standard St. Mark's electrode, and in a second series of 20 normal
      subjects over 50 years, using a new intra-rectal monopolar stimulator that did
      not require finger insertion through the anal canal. RESULTS: In the first
      series, PNTML ranged from 1.8 to 5.6 ms (mean+/-SD 2.94+/-0.8 ms) and correlated
      positively with the age of the subjects (P=0.01, Spearman test). In the second
      series, PNTML ranged from 2.2 to 5.4 ms (3.7+/-0.9 ms) and was similar to that of
      the subjects over 50 years of the first series (3.5+/-0.4 ms) (P=0.35, Mann
      Whitney U test). CONCLUSIONS: This study showed significant effects of age on
      PNTML. This should encourage every examiner to establish age-stratified reference
      values of PNTML for older age groups. In addition, we showed the advantage of
      using a new type of intra-rectal stimulator to reduce the patient's discomfort by
      avoiding finger insertion to stimulate the pudendal nerve.

PMID- 11222970
TI  - Overlap of attention and movement-related activity in lateralized event-related
      brain potentials.
AB  - OBJECTIVE: In tasks that involve lateralized visuospatial attention and a
      lateralized motor response, the associated brain electrical potentials, i.e. the
      attention-related N2pc and the lateralized readiness potential, typically overlap
      at central scalp sites. The manifestation of the N2pc at central electrode sites
      is commonly attributed to electric volume conduction effects, assuming the N2pc
      to be generated in occipito-temporal brain areas. We evaluated this explanation
      in a simulation study. METHODS: Using a forward modeling approach with a
      realistically shaped volume conduction model, we calculated the range of
      amplitude ratios between occipital and central electrode sites when a single
      source is assumed in area V4 or in area TO, at the temporo-occipital convexity.
      RESULTS: A comparison of the simulated amplitude ratios with reported data
      indicates that volume conduction effects from the investigated source origins in
      the occipito-temporal region are insufficient to explain the experimental data.
      CONCLUSIONS: We conclude that the anterior spread of the N2pc from its occipito
      temporal maximum to central electrode sites is probably due to simultaneous
      attention-related activity in posterior and central brain areas.

PMID- 11222971
TI  - Differences between the N1 waves of the responses to interaural time and
      intensity disparities: scalp topography and dipole sources.
AB  - OBJECTIVES: Being the two complementary cues to directional hearing, interaural
      time and intensity disparities (ITD and IID, respectively), are known to be
      separately encoded in the brain stem. We address the question as to whether their
      codes are collapsed into a single lateralization code subcortically or they reach
      the cortex via separate channels and are processed there in different areas.
      METHODS: Two continuous trains of 100/s clicks were dichotically presented. At 2
      s intervals either an interaural time delay of 1ms or an interaural level
      difference of 20 dB (HL) was introduced for 50 ms, shifting the intracranial
      sound image laterally for this brief period of time. Long-latency responses to
      these directional stimuli, which had been tested to evoke no potentials under
      monotic or diotic conditions, as well as to sound pips of 50 ms duration were
      recorded from 124 scalp electrodes. Scalp potential and current density maps at
      N1 latency were obtained from thirteen normal subjects. A 4-sphere head model
      with bilaterally symmetrical dipoles was used for source analysis and a simplex
      algorithm preceded by a genetic algorithm was employed for solving the inverse
      problem. RESULTS: Inter- and intra-subject comparisons showed that the N1
      responses evoked by IID and ITD as well as by sound pip stimuli had significantly
      different scalp topographies and interhemispheric dominance patterns. Significant
      location and orientation differences between their estimated dipole sources were
      also noted. CONCLUSIONS: We conclude that interaural time and intensity
      disparities (thus the lateral shifts of a sound image caused by these two cues)
      are processed in different ways and/or in different areas in auditory cortex.

PMID- 11222972
TI  - Near-DC magnetic fields following a periodic presentation of long-duration
      tonebursts.
AB  - OBJECTIVES: The purpose of this study was to determine the time course of low
      frequency (<0.1 Hz) magnetic field components evoked by long-duration tonebursts.
      The following two questions were of central interest. Does the sustained field
      (SF) show adaptation as described before for the sustained potential (SP)? How
      does the field amplitude return to the pre-stimulus baseline after stimulus
      offset? METHODS: Neuromagnetic measurements were done with a 37-channel first
      order gradiometer system. The stimulus was a 1 kHz toneburst of 10 s duration
      presented at fixed 20 s intervals. The averaged data (high-pass filtered, 0.03 Hz
      cut-off) were analyzed using the model of an equivalent current dipole with time
      invariant location and orientation (fixed dipole). RESULTS: In the grand average
      of the subjects with the best signal-to-noise ratio, the SF exhibited adaptation
      with a time constant of 3.6 s. After stimulus offset, the amplitude of the dipole
      moment dropped to a lower level within 300 ms and decayed exponentially to the
      baseline thereafter (time constant 2.7 s). CONCLUSIONS: A two-component model is
      proposed: One component roughly follows the envelope of the stimulus, the other
      behaves like a leaky integrator. A better understanding of near-DC fields appears
      to be crucial for the understanding of the relationship between
      magnetoencephalography and other functional imaging techniques like functional
      magnetic resonance imaging and positron emission tomography.

PMID- 11222973
TI  - Auditory response following vocalization: a magnetoencephalographic study.
AB  - OBJECTIVE: We recorded vocalization-related cortical fields (VRCF) under complete
      masking of a subject's own voice to identify the auditory component evoked by a
      subject's own voice in the VRCF complex. METHODS: We recorded VRCF during simple
      vowel (/u/) vocalization in 10 right-handed healthy volunteers under two
      conditions: (1) no masking (control) and (2) masking of the subject's own voice
      by weighted-white noise during vocalization. In the second experiment, we
      recorded auditory evoked magnetic fields (AEF) following stimulation of a speech
      sound applied by voice-recorder. RESULTS: The onset of VRCF appeared gradually
      before the vocalization onset, and a clear phase-reversed deflection was
      identified after the onset of vocalization. The difference waveform obtained by
      subtracting the VRCF of the masking condition from that of the control showed a
      deflection (1M) at 81.3+/-20.5 (mean+/-SD) ms after the onset of vocalization,
      but there was no consistent deflection before the vocalization onset. The AEF
      following voice sound in the second experiment showed the M100 component at
      94.3+/-18.4 ms. The equivalent current dipole of the 1M component for different
      waveforms was located close in the auditory cortex to that of the M100 for AEF
      waveforms in each hemisphere. CONCLUSION: We successfully separated the auditory
      feedback response from the VRCF complex, using an adequate masking condition
      during vocalization of a subject's own voice. The masking effect was crucial to
      the auditory feedback process after the onset of vocalization. The present
      results suggested that the 1M component was mainly generated from the auditory
      feedback process by the subject's own voice. The activated auditory area for
      simple own voice might be similar to that for simple external sound.

PMID- 11222974
TI  - Sleep spindle characteristics in healthy subjects of different age groups.
AB  - OBJECTIVES: Few studies have quantified the various characteristics of sleep
      spindles (SS) in groups of normal human subjects. The aim of the present study
      was to look at the effects of age on the number, density, duration, intra-spindle
      frequency, and periodicity of SS during stage 2 sleep in normal subjects of
      different age groups. METHODS: Thirty-six healthy subjects participated in the
      study. They were divided into 6 age groups: 10-19, 20-29, 30-39, 40-49, 50-59 and
      60-69 years. RESULTS: The results show that there is a progressive decrease in SS
      number, density, duration and a progressive increase in intra-spindle frequency
      with age. These changes occur mainly in the first 4 decades, except for SS number
      and density, for which the changes seem to continue until the sixth decade. The
      present study also reveals a clear periodicity of SS in human sleep. SS occur
      every 3-6 s, and the modal value of inter-spindle intervals increases with aging.
      CONCLUSIONS: The progressive decrease in the number of SS and slow-wave sleep
      time with age suggests that SS are part of sleep promoting mechanisms. The
      negative correlation found between SS density and sleep efficiency in the present
      study is congruent with the sleep maintenance role of SS.

PMID- 11222975
TI  - Characterization of the mu rhythm during rapid eye movement sleep.
AB  - OBJECTIVE: The rolandic mu rhythm, a resting activity of somatosensory cortex, is
      a striking feature of the waking human electroencephalogram. This study will
      demonstrate that activity with identical features occurs during rapid eye
      movement (REM) sleep. METHODS: Eye and chin leads were added during prolonged
      closed circuit television (video) electroencephalographic (EEG) recording with
      scalp (12 patients) or subdural electrodes including 64 contract grids over the
      frontoparietal cortices (5 patients). Sleep staging was performed by reformatting
      into standard polysomnography montages (using two EEG channels, and eye and chin
      channels) and applying standard scoring criteria. The recordings were then
      reviewed using all EEG channels to assess rhythmic EEG activity by a reader
      blinded to the sleep staging. RESULTS: During scalp recordings, 7-10 Hz central
      rhythms were seen during wakefulness in 7 patients, with 6 of these also having
      similar rhythms during REM sleep. Similar activity was seen over somatosensory
      cortex during wakefulness and REM in all invasively recorded patients. This
      activity was blocked by contralateral body movement or contralateral
      somatosensory stimuli, even during REM sleep. It was absent in other sleep
      stages. CONCLUSIONS: This REM sleep activity recapitulates all the
      characteristics of the waking rolandic mu rhythm. This demonstrates functional
      similarity between the states of wakefulness and REM sleep.

PMID- 11222976
TI  - Heart rate changes during sleep in response to experimental thermal (nociceptive)
      stimulations in healthy subjects.
AB  - OBJECTIVE: During wakefulness, nociceptive thermal stimulation can trigger a
      rapid and transient rise in heart rate (HR). During sleep, HR variations are
      different across sleep stages; HR is more variable in stage 2 and in REM than in
      stages 3 and 4. The aim of this study was to assess the HR response to
      experimental thermal stimulation during different sleep stages. METHODS: Eight
      young subjects free of sleep and pain problems, underwent a night of
      polysomnographic recording during which experimental thermal stimulations were
      applied. During all sleep stages (St), a series of cold, warm/control and heat
      pain stimulations were applied over the shoulder skin by means of a water-driven
      system. Variation of HR interval was measured for 6 s before and for 6 s during
      the thermal stimulation. RESULTS: In comparison to control warm stimulation,
      experimental nociceptive thermal stimulation induced a significant rise in HR
      during sleep; HR increased by 7% in St 2, 5.4% in St 3&4, and by 4.3% in REM
      sleep. CONCLUSION: The brief increase in cardiac activity with experimental
      nociceptive stimulation suggests that during sleep, the autonomic-cardiac nervous
      system remains reactive to external sensory inputs and is part of the
      physiological response to preserve body safety and sleep integrity in the face of
      potentially harmful stimulation.

PMID- 11222977
TI  - Scalp electrode impedance, infection risk, and EEG data quality.
AB  - OBJECTIVES: Breaking the skin when applying scalp electroencephalographic (EEG)
      electrodes creates the risk of infection from blood-born pathogens such as HIV,
      Hepatitis-C, and Creutzfeldt-Jacob Disease. Modern engineering principles suggest
      that excellent EEG signals can be collected with high scalp impedance (
      approximately 40 kOmega) without scalp abrasion. The present study was designed
      to evaluate the effect of electrode-scalp impedance on EEG data quality. METHODS:
      The first section of the paper reviews electrophysiological recording with modern
      high input-impedance differential amplifiers and subject isolation, and explains
      how scalp-electrode impedance influences EEG signal amplitude and power line
      noise. The second section of the paper presents an experimental study of EEG data
      quality as a function of scalp-electrode impedance for the standard frequency
      bands in EEG and event-related potential (ERP) recordings and for 60 Hz noise.
      RESULTS: There was no significant amplitude change in any EEG frequency bands as
      scalp-electrode impedance increased from less than 10 kOmega (abraded skin) to 40
      kOmega (intact skin). 60 Hz was nearly independent of impedance mismatch,
      suggesting that capacitively coupled noise appearing differentially across
      mismatched electrode impedances did not contribute substantially to the observed
      60 Hz noise levels. CONCLUSIONS: With modern high input-impedance amplifiers and
      accurate digital filters for power line noise, high-quality EEG can be recorded
      without skin abrasion.

PMID- 11222979
TI  - Self-initiation of EEG-based communication in paralyzed patients.
AB  - OBJECTIVES: Severely paralyzed patients could learn to voluntarily generate slow
      cortical potential (SCP) shifts in their electroencephalogram and to use these
      signals to operate a communication device. To enhance the patients' autonomy, the
      present study describes the development of a permanently available communication
      system that can be turned on and off by locked-in patients without external
      assistance. A skill necessary for turning the system on is the ability to
      regulate one's slow potentials in the absence of continuous feedback. METHODS: A
      stepwise learning approach was employed to train two paralyzed patients to
      regulate their SCPs without continuous feedback. Elements of the original
      communication system were gradually removed and elements of the new stand-by mode
      were introduced. RESULTS: At the end of the learning procedure, both patients
      achieved correct response rates of above 84% in training sessions without
      continuous feedback. This skill enabled them to turn the communication device on
      and off without assistance from others. CONCLUSIONS: These findings suggest that
      severely paralyzed individuals can learn to operate an EEG-based communication
      device autonomously.

PMID- 11222978
TI  - A convenient method for detecting electrolyte bridges in multichannel
      electroencephalogram and event-related potential recordings.
AB  - Dense electrode arrays offer numerous advantages over single channel
      electroencephalogram/event-related potential (EEG/ERP) recordings, but also
      exaggerate the influence of common error sources arising from the preparation of
      scalp placements. Even with conventional low density recordings (e.g. 30-channel
      Electro-Cap), over-application of electrode gel may result in electrolyte leakage
      and create low impedance bridges, particularly at vertically-aligned sites (e.g.
      inferior-lateral). The ensuing electrical short produces an artificial similarity
      of ERPs at neighboring sites that distorts the ERP topography. This artifact is
      not immediately apparent in group averages, and may even go undetected after
      visual inspection of the individual ERP waveforms. Besides adding noise variance
      to the topography, this error source also has the capacity to introduce
      systematic, localized artifacts (e.g. add or remove evidence of lateralized
      activity). Electrolyte bridges causing these artifacts can be easily detected by
      a simple variant of the Hjorth algorithm (intrinsic Hjorth), in which spatial
      interelectrode distances are replaced by an electrical analog of distance (i.e.
      the variances of the difference waveforms for all pairwise combinations of
      electrodes). When a low impedance bridge exists, the Hjorth algorithm identifies
      all affected sites as flat lines that are readily distinguishable from Hjorth
      waveforms at unbridged electrodes.

PMID- 11222980
TI  - Weighted averaging of steady-state responses.
AB  - OBJECTIVE: To compare weighted averaging and artifact-rejection to normal
      averaging in the detection of steady-state responses. METHODS: Multiple steady
      state responses were evoked by auditory stimuli modulated at rates between 78 and
      95 Hz. The responses were evaluated after recording periods of 3, 6 and 10 min,
      using 5 averaging protocols: (1) normal averaging; (2) sample-weighted averaging;
      (3) noise-weighted averaging; (4) amplitude-based artifact-rejection; and (5)
      percentage-based artifact rejection. The responses were analyzed in the frequency
      domain and the signal-to-noise ratio was estimated by comparing the signals at
      the modulation-frequencies to the noise at adjacent frequencies. RESULTS:
      Weighted averaging gave the best signal-to-noise ratios. Artifact-rejection was
      better than normal averaging but not as good as weighted averaging. Responses
      that were not significant with normal averaging became significant with weighted
      averaging much more frequently than vice versa. False alarm rates did not
      significantly differ among the protocols. The advantage of weighted averaging was
      especially evident when stimuli were presented at lower intensities or when
      smaller amounts (e.g. only 3 or 6 min) of data were evaluated. Weighted averaging
      was most effective when the background noise levels were variable. Weighted
      averaging underestimated the amplitude of the responses by about 2%. CONCLUSION:
      Weighted averaging should be used instead of normal averaging for detecting
      steady-state responses.

PMID- 11222981
TI  - Elicitation of predictable immune responses by using live bacterial vectors.
AB  - There is an increasing need for novel vaccines able to stimulate efficient and
      long-lasting responses, which have also low production costs. To confer
      protective immunity following vaccination, the adequate type of response should
      be elicited. Vaccines based on attenuated bacterial carriers have contained
      production and delivery costs, and are able to stimulate more potent immune
      responses than non-replicating formulations. The improved knowledge on carrier
      physiology and host response, the availability of different mutants and highly
      sophisticated expression tools, and the possibility of co-administering
      modulators enable to trigger predictable responses according to the specific
      needs. Recent studies support the use of attenuated bacteria not only as
      conventional carriers, but also as a delivery system for DNA vaccines against
      infectious agents and tumors. In this review we discuss the most widely used
      bacterial carrier systems for either antigens or nucleic acid vaccines, and the
      strategies which have been successfully exploited to modulate the immune
      responses elicited.

PMID- 11222983
TI  - Target gene identification from expression array data by promoter analysis.
AB  - DNA microchips and expression arrays yield enormous amounts of data linking cDNA
      sequences to gene expression patterns. This now allows the characterization of
      gene expression in normal and diseased tissues as well as the response of tissues
      to the application of therapeutic reagents. Software currently exists to analyze
      DNA array/chip data with respect to corresponding mRNA sequences, which
      facilitates the precise determination of when and where certain groups of genes
      are expressed. The information concerning transcriptional regulatory networks
      responsible for the observed expression patterns is not contained within the cDNA
      sequences used to generate the arrays, but resides often within the promoter
      sequences of the individual genes (and/or enhancers). The complete sequence of
      the human genome will provide the molecular basis for the identification of such
      regulatory regions. Promoter sequences for specific cDNAs can be obtained
      reliably from genomic sequences simply by exon mapping. Promoter prediction tools
      can also be used to locate promoters directly in the genomic sequence in many
      cases in which cDNAs are 5'-incomplete. Once sufficient numbers of promoter
      sequences have been obtained, the comparative promoter analysis of the co
      regulated genes and groups of genes can be applied in order to generate models
      describing the higher order levels of the transcription factor binding site
      organization within these promoter regions. As evident from several examples,
      this approach can identify promoter modules responsible for the common regulation
      of promoters solely by the application of bioinformatics methods. Such modules
      represent the molecular mechanisms through which regulatory networks influence
      gene expression. Another advantage of this approach is that it also provides a
      powerful alternative for elucidating functional features of genes with no
      detectable sequence similarity, by linking them to other genes on the basis of
      their common promoter structures.

PMID- 11222982
TI  - Enhanced green fluorescent protein as a useful tag for rapid identification of
      homozygous transgenic mice.
AB  - We developed a technique that simplifies the process of confirming homozygous
      transgenics at preimplantation stages, which are the earliest stages used in test
      breeding, using enhanced green fluorescent protein as a tag. All the blastocysts
      obtained by mating with the combination of Tg/Tg male (homozygous for transgene)
      x +/+ female exhibited fluorescence.

PMID- 11222984
TI  - Molecular characterization of minimal residual cancer cells in patients with
      solid tumors.
AB  - The failure to reduce the mortality of patients with solid tumors is mainly a
      result of the early dissemination of cancer cells to secondary sites, which is
      usually missed by conventional diagnostic procedures used for tumor staging. PCR
      was shown to be superior to conventional techniques in detecting circulating
      tumor cells and micrometastases allowing the identification of one tumor cell in
      up to 10(7) normal cells in various sources such as blood, bone marrow, lymph
      nodes, urine or stool. The methods used are based on the detection of either
      genomic alterations in oncogenes and tumor suppressor genes or on the mRNA
      expression of tissue-specific and tumor-associated genes. The additional
      implementation of techniques for cancer cell purification had a significant
      impact on analytical sensitivity and specificity of MRCC detection. For patients
      with e.g. melanoma, breast, colorectal or prostate cancer it was demonstrated
      that the presence of disseminated cancer cells defines a subgroup of patients
      with reduced time to recurrence. The possibility to use easily accessible body
      fluids as a source for MRCC detection enables longitudinal observations of the
      disease. In this review we discuss the potential of molecular characterization of
      MRCC as a tool to improve prognostication, therapy selection and drug targeting
      as well as therapy monitoring.

PMID- 11222985
TI  - DNA architecture and transcriptional regulation of the Escherichia coli
      penicillin amidase (pac) gene.
AB  - The transcriptional regulation of Escherichia coli ATCC11105 penicillin amidase
      (pac) gene was studied by modifying DNA sequences responsible for promoter
      activation by cyclic AMP receptor protein (CRP). The nucleotide sequence of the
      5'-flanking region of the pac gene contains putative tandem CRP binding sites
      positioned at -69/-70 and at -111/-112 with respect to the transcriptional start
      site. Our results obtained with either point mutations or insertion or deletion
      mutants (each of which rotated the helix structure at the CRP binding site one
      half turn) showed significant decrease of penicillin amidase (PA) activity,
      suggesting the CRP as a major activator. In this study, the evidence for the
      importance of spacing between tandem binding sites for CRP as well as for their
      location related to the promoter core sequence has been provided. Involvement of
      integration host factor (IHF) as an additional regulatory protein in the pac gene
      transcription regulation was also analyzed. It is shown that activation of the
      pac gene transcription is elevated by IHF.

PMID- 11222986
TI  - Central corticotropin releasing factor (CRF) and adrenergic receptors mediate
      hemodynamic responses to cocaine.
AB  - Cocaine administration evokes cardiovascular responses that are variable in rats
      such that the pressor response is attributable to either a large increase in
      systemic vascular resistance and a decrease in cardiac output (vascular
      responders) or a smaller increase in systemic vascular resistance and no change
      or an increase in cardiac output (mixed responders). This study was designed to
      determine the role of central corticotropin releasing factor (CRF) and adrenergic
      receptors in mediating specific hemodynamic response patterns. Rats were
      instrumented for ascending aortic blood flow determination (cardiac output) using
      a pulsed Doppler system, arterial pressure measurement and for intravenous and
      intracerebroventricular (icv) administration of drugs. After characterizing the
      hemodynamic response pattern in individual rats to cocaine (5 mg/kg, i.v., 4-6
      trials), selective receptor antagonists were administered icv 10 min before
      cocaine (5 mg/kg, i.v.). Pretreatment with the CRF antagonist alpha-helical CRF(9
      41) (10 microg/5 microl, icv) prevented the decrease in cardiac output in
      vascular responders without altering hemodynamic responses to cocaine in mixed
      responders. Astressin (5 microg/5 microl, icv) exerted a similar effect in
      vascular responders. The alpha(2) receptor antagonist, yohimbine (3
      microg/microl, icv) also prevented the decrease in cardiac output in vascular
      responders. Lower doses of alpha-helical CRF(9-41) (1 and 3 microg) were
      ineffective whereas higher doses of either CRF antagonist were lethal within 24
      h. In contrast, propranolol (3 or 30 microg, icv) pretreatment enhanced the
      cocaine-induced decrease in cardiac output and increase in systemic vascular
      resistance noted in vascular responders and resulted in a decrease in cardiac
      output in mixed responders. We conclude that CRF and adrenoceptors in the CNS
      play an important role in determining the hemodynamic response pattern to
      cocaine. Furthermore, central beta-adrenoceptors may be responsible for the
      reported effects of intravenous propranolol on cocaine-induced responses.

PMID- 11222987
TI  - Axon terminals containing CGRP-immunoreactivity form synapses with CRF- and Met
      enkephalin-immunopositive neurons in the laterodorsal division of the bed nucleus
      of the stria terminalis in the rat.
AB  - The lateral division of the bed nucleus of the stria terminalis (BSTL) is an
      important forebrain structure that relays information between limbic structures
      and the hypothalamus. The BSTL displays a very dense calcitonin gene-related
      peptide-immunoreactive (-ir) fiber terminal network, and contains a substantial
      number of the corticotropin releasing factor (CRF)-ir neurons. Several Met
      enkephalin-ir perikarya have also been observed in the BSTL. The distributions of
      CRF- and Met-enkephalin-ir neurons and that of the calcitonin gene-related
      peptide (CGRP)-ir axon terminals overlap within the BSTL, suggesting synaptic
      connections between CRF- and Met-enkephalin-ir neurons and axon terminals
      immunoreactive for CGRP. Double staining immunohistochemistry revealed that CGRP
      ir axon terminals were within close proximity to dendrites or perikarya of
      corticotropin releasing factor and Met-enkephalin-ir neurons. When viewed at the
      electron microscopic level, axodendritic or axosomatic synapses between CGRP-ir
      fiber terminals and neurons immunoreactive for CRF and Met-enkephalin were
      detected. Most of the CRF-ir neurons project to brainstem centers, which modulate
      the physiological changes accompanying stress, whereas the Met-enkephalin-ir
      perikarya are most likely interneurons that often colocalize with GABA. The
      parabrachial nucleus, a vital autonomic center, is the primary source of CGRP-ir
      fiber terminals to the BSTL. The synaptic contacts between the CGRP axon
      terminals and CRF- and Met-enkephalin-ir neurons underlie the importance of
      connections between autonomic brainstem centers and BSTL, which can be
      fundamental in the modulatory control of endocrine, physiological and behavioral
      responses during stress.

PMID- 11222988
TI  - Alpha-helical-corticotropin-releasing hormone reverses anxiogenic effects of C
      type natriuretic peptide in rats.
AB  - Previously we have shown that atrial natriuretic peptide (ANP) has anxiolytic
      like properties after intraperitoneal, intracerebroventricular and intraamygdala
      infusion in rats. Since C-type natriuretic peptide (CNP) exerts endocrine and
      behavioral effects opposing those of ANP, we characterized the behavioral
      properties of CNP after icv infusion in rats by their performance in the elevated
      plus maze with and without the corticotropin-releasing hormone (CRH) antagonist
      alpha-helical-CRH (alpha-CRH). Low CNP doses of 0.05 microg icv or 0.1 microg icv
      did not significantly influence the behavior of rats in the plus maze. At higher
      doses (0.5 microg, 2 microg, 5 microg icv) CNP had distinct anxiogenic
      properties. Our hypothesis that corticotropin-releasing hormone (CRH) is
      involved, which elicits anxiety-like behavior, was examined by icv
      coadministration of alpha-CRH, an antagonist at CRH-1 and CRH-2-receptors. Icv
      alpha-CRH alone had no intrinsic anxiolytic properties at a dose of 25 microg.
      The anxiogenic effects of 2 microg CNP icv seen in the plus maze were entirely
      blocked by alpha-CRH. Directly after exposition ACTH and corticosterone levels
      did not differ between the groups, but after 30 min ACTH levels were
      significantly higher in the CNP-treated group compared to alpha-CRH/CNP-treated
      animals. Corticosterone was found significantly lowered in the alpha-CRH/saline
      group compared to the CNP treated group but not compared to saline controls. Our
      data suggest opposing effects of CNP and ANP on anxiety-related behavior and
      neuroendocrine regulation in rats, which appear to be mediated via different
      receptor occupation and brain regions, and by a CRH-dependent mechanism.

PMID- 11222989
TI  - Role of CRF receptor 1 in central CRF-induced stimulation of colonic propulsion
      in rats.
AB  - The CRF receptor subtype mediating the colonic and gastric motor responses to
      central CRF was investigated in conscious rats. CRF (0.6 microg/rat) injected
      intracerebroventicularly (i.c.v.) or 1 h water avoidance stress stimulated
      defecation (pellet/60 min: 4.1+/-1.0 and 8.7+/-0.7 respectively vs. 0.3+/-0.3 in
      i.c.v. vehicle/no stress). The CRF receptor 1 (CRF-R1) antagonist, NBI-27914 (50
      100 microg/rat) injected i.c.v., abolished the colonic response to i.c.v. CRF and
      dose-dependently reduced that induced by water avoidance stress. NBI-27914 (100
      microg/rat) injected peripherally did not influence the defecatory response to
      stress. The peptide CRF-R1/R2 antagonist, astressin (10 microg/rat, i.c.v.)
      inhibited the colonic motor response to i.c.v. CRF and stress similarly as NBI
      27914 injected i.c.v. at 100 microg/rat. Intracisternal (i.c.) injection of
      astressin (10 microg/rat) also completely prevented CRF (0.6 g, i.c.)-induced
      delayed gastric emptying while i.c. NBI-27914 (50 or 100 microg) had no effect.
      These results indicate a differential role of central CRF receptor subtypes in
      the colonic stimulatory and gastric inhibitory motor responses to central CRF and
      that the CRF component of stress-related activation of colonic expulsion is
      primarily mediated by CRF-R1.

PMID- 11222990
TI  - The effects of cooling and rewarming on the neuronal activity of pyramidal
      neurons in guinea pig hippocampal slices.
AB  - To investigate the reversibility of neuronal functions during deep and mild
      hypothermia, we have examined changes in membrane properties of pyramidal neurons
      of the CA3 region of hippocampal slices during cooling and rewarming (8
      approximately 37 degrees C) of the perfusion medium. Hypothermia reduced the
      excitatory postsynaptic potential (EPSP) slope in a temperature dependent manner,
      but the EPSP amplitude was enhanced transiently between 30 and 25 degrees C. In
      observing spikes generated by either orthodromic stimulation or by direct
      intracellular current injection, the critical threshold for spike generation was
      decreased transiently at a temperature of 30 degrees C. In addition, the numbers
      of spikes were increased transiently regardless of the progressive prolongation
      of spike duration and latency with cooling. The resting membrane potential was
      stable from 37 to 20 degrees C. However, this potential showed a depolarizing
      shift at 15 degrees C. The neuronal activities, including membrane properties,
      recovered fully when the temperature was raised to 35 degrees C even from a low
      of 15 degrees C. In addition, field population spikes (PS) recorded in the
      pyramidal cell layer showed a complete reversibility after long-term severe
      hypothermia (8 degrees C). These results suggest that synaptic function, neuronal
      excitability and membrane properties maintain reversibility during deep
      hypothermia, as well as in mild hypothermia.

PMID- 11222991
TI  - Effects of glial glutamate transporter inhibitors on intracellular Na+ in mouse
      astrocytes.
AB  - The effects of inhibitors of the glial Na+/glutamate co-transporter on the
      intracellular Na+ concentration ([Na+](i)) were investigated in mouse cortical
      astrocytes. [Na+](i) was monitored by fluorescence microscopy on single
      astrocytes using the Na+-sensitive probe sodium-binding benzofuran isophtalate.
      Application of the competitive inhibitors threo-beta-hydroxyaspartate (THA) and
      trans-pyrrolidine-2,4-dicarboxylic acid (t-PDC) resulted in robust and reversible
      increases in [Na+](i) that were comparable in shape to the response to glutamate
      but about twice lower in amplitude. As previously observed with glutamate, the
      amplitude of the [Na+](i) response to these compounds was concentration-dependent
      with EC(50) values of 11.1 microM (THA) and 7.6 microM (t-PDC), as was the
      initial rate of [Na+](i) rise (EC(50) values of 14.8 microM for THA and 11.5
      microM for t-PDC). Both compounds diminished the response to subsequent glutamate
      applications, possibly because of an inhibitory effect of the intracellularly
      accumulated compounds. In comparison, the newly-developed compound threo-beta
      benzyloxyaspartate (TBOA) alone did not cause any significant alteration of
      [Na+](i) up to a concentration of 500 microM . TBOA inhibited the [Na+](i)
      response evoked by 200 microM glutamate in a concentration-dependent manner with
      IC(50) values of 114 and 63 microM, as measured on the amplitude and the initial
      rate, respectively. The maximum inhibition of glutamate-evoked [Na+](i) increase
      by TBOA was approximately 70%. The residual response persisted in the presence of
      a non-NMDA receptor antagonist or the inhibitor of the GLT-1 glutamate
      transporters, dihydrokainate (DHK). In view of the complete reversibility of its
      effects, TBOA represents a very useful pharmacological tool for studies of
      glutamate transporters.

PMID- 11222992
TI  - Repeated electroconvulsive stimulation, but not antidepressant drugs, induces
      mossy fibre sprouting in the rat hippocampus.
AB  - Electroconvulsive stimulation (ECS) has been shown recently to induce axonal
      sprouting of granule cells in the rodent hippocampus. This may relate to the
      clinical efficacy of electroconvulsive therapy (ECT) in humans. We compared the
      effects of three different clinically effective antidepressant treatments on
      mossy fibre sprouting in the rat dentate gyrus using Timm's histochemistry: (1)
      repeated spaced ECS; (2) daily administration for 4 weeks of the serotonin re
      uptake inhibitor fluoxetine (1 mg/kg); and (3) daily administration for 4 weeks
      of the noradrenaline re-uptake inhibitor desipramine (5 mg/kg). The effect of
      subconvulsive electrical stimulation was also examined. Repeated ECS-induced
      sprouting while subconvulsive stimulation (which is ineffective clinically) did
      not. The two well-established chemical antidepressant therapies were also
      ineffective, indicating that induction of mossy fibre sprouting is not a common
      property of effective antidepressant agents. It is possible that the ability to
      induce sprouting might relate to the superior efficacy of ECT when compared to
      chemical antidepressants in clinical practice. Alternatively, it may contribute
      to the transient cognitive impairment that accompanies ECS in humans and other
      species.

PMID- 11222993
TI  - Responses of spinal neurones to cutaneous and dorsal root stimuli in rats with
      mechanical allodynia after contusive spinal cord injury.
AB  - The firing of neurones in spinal segments adjacent to a contusive T13 spinal cord
      injury was characterised in anaesthetised rats. Three groups of rats were
      examined: (1) allodynic spinally injured, (2) non-allodynic spinally injured and
      (3) normal, uninjured. Spinal cord field potentials evoked by electrical dorsal
      root stimulation and the responses of 207 dorsal horn neurones to mechanical
      stimuli applied to the skin were studied. Within the lesioned spinal segment few
      active neurones were encountered and field potentials were absent. Depolarising
      field potentials recorded rostral to the lesion were reduced in both allodynic
      and non-allodynic animals compared to uninjured controls, while those recorded in
      caudal segments were enhanced in allodynic animals. Neuronal recordings revealed
      that allodynia was associated with exaggerated responses, including
      afterdischarges, to innocuous and noxious mechanical stimuli in a proportion of
      wide dynamic range, but not low threshold, neurones. These changes were observed
      both rostral and caudal to the site of injury. The results suggest that an
      increased responsiveness of some dorsal horn neurones in segments neighbouring a
      contusive spinal cord injury may contribute to the expression of mechanical
      allodynia. It is proposed that a relative lack of inhibition underlies altered
      cell responses.

PMID- 11222994
TI  - Metabolic activity of the human ventromedial nucleus neurons in relation to sex
      and ageing.
AB  - The ventromedial nucleus (VMN) in animals is involved in a number of sexually
      dimorphic behaviors, including reproduction, and is a well-documented target for
      sex steroids. In rats and in lizards, it is also characterized by the presence of
      structural sexual dimorphisms. In the present study, we determined whether the
      metabolic activity of human ventromedial nucleus neurons was sex- or age-related.
      The size of the immunocytochemically defined Golgi apparatus (GA) and cell
      profiles were determined as measures for neuronal metabolic activity in 12 male
      and 16 female control brains sub-divided into four groups with the dividing line
      being the age of 50. It appeared that the size of the GA relative to cell size
      was 34% larger in young women (<50 years old) than in young men and was 25%
      larger in elderly men (> or = 50 years old) than in young men. In addition, the
      GA/cell size ratio correlated significantly with age in men and not in women. Our
      data suggest that androgens play an inhibitory role with respect to the metabolic
      activity of the human VMN neurons.

PMID- 11222995
TI  - Serotonin transporter localization in the hamster suprachiasmatic nucleus.
AB  - Pacemaker cells within the hamster suprachiasmatic nucleus generate circadian
      rhythms. The suprachiasmatic nucleus is heavily innervated by serotonin axons
      originating in the median raphe nuclei. Consequently, serotonergic agonists and
      antagonists or agents that alter levels of serotonin in the synapse following
      transmission can modulate many aspects of circadian rhythmicity. Examples of the
      latter are some antidepressants and the stimulant amphetamine that bind to the
      serotonin transporter and block serotonin reuptake. It has been hypothesized that
      circadian rhythm dysfunction may be involved in depression, and that the efficacy
      of certain antidepressants in treating depression may involve an alteration of
      serotonin levels and certain circadian rhythm parameters. However, although the
      hamster is the behavioral model of choice for the study of circadian rhythms, the
      identification of serotonin transporters in this species has not been reported.
      Therefore, in this report we describe the distribution of the serotonin
      transporter in the hamster suprachiasmatic nucleus using immunohistochemical
      techniques. Our results demonstrate a dense labeling of the serotonin transporter
      throughout the ventral and medial regions of the suprachiasmatic nucleus, a
      pattern that overlaps the distribution of serotonergic afferents in this nucleus.
      Amphetamines and certain antidepressants may serve as substrates for this
      transporter and elicit chronopharmacological activity by elevating serotonin
      levels in the suprachiasmatic nucleus.

PMID- 11222996
TI  - Dorsal horn lesion resulting from spinal root avulsion leads to the accumulation
      of stress-responsive proteins.
AB  - The aim of this study was to demonstrate acute to subacute molecular episodes in
      the dorsal horn following root avulsion using immunohistochemical methods with
      the markers for synapses, astrocytes and such stress-responsive molecules as heat
      shock proteins (Hsps) and p38 MAP kinase (p38). Among them, Hsp27 was accumulated
      selectively in the injured substantia gelatinosa 24 h after avulsion injury. The
      localization of Hsp27 in astrocytes within the substantia gelatinosa was
      confirmed by the double immunofluorescence method using anti-Hsp27 antibody and
      either anti-synaptophysin antibody or anti-glutamine synthetase antibody and by
      immunoelectron microscopy for Hsp27. The pattern of Hsp27 expression subsequently
      changed from glial pattern to punctate pattern by 7 days. Immunoelectron
      microscopy revealed that the punctate pattern in the subacute stage corresponded
      to distal parts of the astrocytic processes. Hsp27 immunoreaction was decreased
      21 days after root avulsion. In the distal axotomy model, Hsp27 was accumulated
      later in the ipsilateral dorsal horn in a punctate pattern from 7 days after the
      axotomy. Phosphorylation of p38 was detected in microglia in the dorsal horn
      following both avulsion and axotomy. Substance P was slightly decreased in the
      injured substantia gelatinosa in both the avulsion and axotomy models around 14
      21 days. We conclude that Hsp27 is a useful marker for demonstrating dorsal horn
      lesions following avulsion injury and that avulsion injury may induce Hsp27 in
      the dorsal horn more rapidly than distal axotomy.

PMID- 11222997
TI  - CPI-1189 attenuates effects of suspected neurotoxins associated with AIDS
      dementia: a possible role for ERK activation.
AB  - Individuals infected with the human immunodeficiency virus (HIV) often experience
      a dementia characterized by mental slowing and memory loss. Motor dysfunction may
      also accompany this condition. The pathogenesis of the dementia is not known, but
      microscopic examination of brain tissue from those afflicted shows evidence of
      chronic inflammation, reactive gliosis and cell death. Neurotoxic factors
      produced from activated macrophage or microglial cells such as tumor necrosis
      factor-alpha (TNFalpha), gp120 and quinolinic acid have been implicated as agents
      for the cell death which often appears to occur by an apoptotic mechanism. CPI
      1189, a drug currently undergoing clinical evaluation as a treatment for the
      dementia associated with AIDS, is shown in this paper to mitigate apoptosis
      induced by TNFalpha, gp120, and necrosis induced by quinolinic acid. In addition,
      CPI-1189 mitigates the cell death produced by supernatants from cultured
      macrophages obtained from patients with AIDS dementia. The exact mechanism by
      which CPI-1189 prevents neurotoxicity is not known; however, protection from
      TNFalpha and supernatant-induced toxicity does not appear to involve NFkappaB
      translocation, and appears to be associated with an increase in activated ERK-MAP
      kinase. These findings may have implications for other neurological diseases
      where apoptotic cell death contributes to neurodegeneration.

PMID- 11222998
TI  - Immunohistochemistry of matrix metalloproteinases in reperfusion injury to rat
      brain: activation of MMP-9 linked to stromelysin-1 and microglia in cell
      cultures.
AB  - Reperfusion damages the blood-brain barrier (BBB). Matrix metalloproteinases
      (MMPs) are associated with the opening of the BBB, but their cellular
      localization and activation mechanisms are uncertain. We used
      immunohistochemistry to determine the cellular localization of the MMPs in
      reperfused rat brain, and cell cultures to study their activation. Spontaneously
      hypertensive rats (SHR) had a 90 min middle cerebral artery occlusion (MCAO)
      followed by reperfusion for times from 3 h to 21 days. Frozen sections were
      immunostained with antibodies to gelatinase A (MMP-2), stromelysin-1 (MMP-3), and
      gelatinase B (MMP-9). Sham-operated control rats showed MMP-2 immunostaining in
      astrocytic processes next to blood vessels. After 3 h of the onset of reperfusion
      MMP-2 immunostaining increased in astrocytes. At 24 h immunoreactivity for MMP-3
      and MMP-9 appeared. MMP-3 co-localized with activated microglia (Ox-42+) and
      ischemic neurons (NeuN+). MMP-9 immunostaining was seen at 48 h in endothelial
      cells, neutrophils, and neurons. At 5 and 21 days intense MMP-2 staining was seen
      in reactive astrocytes around the ischemic core. Studies of activation of the MMP
      were done in lipopolysaccharide (LPS)-stimulated astrocyte and microglia
      cultures. Stimulated astrocytes produced an activated form of MMP-2. When
      microglia were stimulated, they activated MMP-9. Immunostaining showed MMP-3 in
      cultures of enriched microglial cells. The hydroxymate-type, MMP inhibitor, BB
      1101, blocked the activation of MMP-2 and MMP-9 by LPS in mixed glial cultures.
      We propose that MMP-2 is normally present in astrocytic end feet, and that during
      ischemia MMP-9 and MMP-3 are produced. MMP-3 in microglia/macrophages may be
      activating proMMP-9. Our results show that a differential expression of MMPs by
      astrocytes, microglia, and endothelial cells at the blood vessels is involved in
      the proteolytic disruption of the BBB.

PMID- 11222999
TI  - Immunohistochemical investigation of caspase-1 and effect of caspase-1 inhibitor
      in delayed neuronal death after transient cerebral ischemia.
AB  - The localization of caspase-1 protein, interleukin-1beta (IL-1beta)-converting
      enzyme, was immunohistochemically examined in the hippocampal CA-1 subfield by a
      transient occlusion of bilateral common carotid arteries in Mongolian gerbils.
      Immunoreactivities for caspase-1 were found in microglias, astrocytes,
      endothelial cells of capillaries and some non-pyramidal neurons. Immunopositive
      microglias increased in number from 3 days until 7 days from the transient
      ischemia, and astrocytes also increased in number from 3 days until 28 days. At
      the electron microscopic level, caspase-1 immunoreaction endproducts were
      associated with Golgi apparatus in glial cells, endothelial cells of blood
      vessels and non-pyramidal neurons. The delayed neuronal death of CA-1 pyramidal
      cells was significantly protected by the treatment of specific caspase-1
      inhibitor (Ac-WEHD-CHO) or broad caspase family inhibitor (z-VAD-FMK). Cell death
      was protected in a dose dependent manner by the former by 43-57%, and by the
      latter by 66-91% when injected at 1 and 10 microg, respectively. On the other
      hand, the protective effect of specific caspase-3 inhibitor (Ac-DMQD-CHO) was
      less significant at higher dose (10 microg) by 33% (P<0.05), and not detectable
      at lower dose (1 microg) by 13% (P=0.27). Furthermore, a significant decrease of
      microglias and astrocytes was found in the CA-1 as well as the reduction of IL
      1beta and caspase-1 immunoreactivities by the treatment of Ac-WEHD-CHO.
      Extravasation of serum albumin was also extremely reduced by this treatment.
      These findings suggest that the inhibition of caspase-1 activity ameliorates the
      ischemic injury by inhibiting the activity of IL-1beta.

PMID- 11223000
TI  - Mu-, delta- and kappa-opioid receptor populations are differentially altered in
      distinct areas of postmortem brains of Alzheimer's disease patients.
AB  - The putative role of the opioid system in cognitive and memory functions prompted
      us to search for possible changes in the cohort of the major opioid receptors,
      mu, delta and kappa, in Alzheimer's disease. The present study examines
      alterations in opioid receptor levels by quantitative autoradiography. These
      experiments were carried out on coronal sections of postmortem brains from
      Alzheimer's disease patients and from aged-matched, dementia-free individuals.
      Brain sections were labeled with the tritiated forms of mu-, delta- and kappa
      opioid ligands; DAMGO ([D-Ala(2),N-Me-Phe(4),Gly-ol(5)]-enkephalin), DPDPE ([D
      Pen2,5]-enkephalin) and bremazocine (in the presence of mu- and delta-ligands),
      respectively. Nonspecific binding was determined in the presence of naloxone (10
      microM). Brain areas analyzed were caudate, putamen, amygdaloid complex,
      hippocampal formation and various cerebral and cerebellar cortices. Image
      analyses of autoradiographs show, that in comparison to the same areas in control
      brain, statistically significant reductions in mu-opioid receptor binding occur
      in the subiculum and hippocampus of Alzheimer's disease brains. Binding of delta
      opioid receptors is also decreased in the amygdaloid complex and ventral putamen
      of Alzheimer's disease brains. In contrast, large increases of kappa-opioid
      receptor binding are found in the dorsal and ventral putamen as well as in the
      cerebellar cortex of Alzheimer's disease brains. Levels of mu- delta- and kappa
      opioid receptor binding are unaltered in the caudate, parahippocampal gyrus and
      occipito-temporal gyrus. These results may suggest an involvement of the
      endogenous opioid system in some of the multitude of effects that accompany this
      dementia.

PMID- 11223001
TI  - Stereotaxic delivery of corticosterone to the amygdala modulates colonic
      sensitivity in rats.
AB  - Episodes of anxiety are often associated with the onset or exacerbation of
      visceral pain in patients with irritable bowel syndrome (IBS). The central
      amygdaloid nucleus (CeA) is a key limbic structure involved in the expression of
      anxiety as well as a major site for regulating autonomic and visceral responses
      to stress. Previous experiments have shown that glucocorticoids can act directly
      at the CeA to increase the level of anxiety in rats. Therefore, the goal of this
      study was to examine the effect of stereotaxic delivery of corticosterone into
      the CeA on the development of visceral hypersensitivity by measuring visceromotor
      response to colorectal distention in rats. Stereotaxic delivery of corticosterone
      to the CeA increases indices of anxiety and produces a hypersensitive colon as
      demonstrated by an exaggerated visceromotor response to colorectal distention in
      the F344 rat strain. Our findings suggest that modulation of anxiety by
      manipulating amygdala function with corticosterone induced colonic
      hypersensitivity via descending neuronal pathways from the CeA.

PMID- 11223002
TI  - Comparison of glucose and lactate as substrates during NMDA-induced activation of
      hippocampal slices.
AB  - It has been postulated that lactate released from astrocytes may be the preferred
      metabolic substrate for neurons, particularly during intense neuronal activity
      (the astrocyte-neuron lactate shuttle hypothesis). We examined this hypothesis by
      exposing rat hippocampal slices to artificial cerebrospinal fluid containing
      either glucose or lactate and either N-methyl-D-aspartate, which activates
      neurons without stimulating astrocytic glucose uptake, or alpha-cyano-4
      hydroxycinnamate, which blocks monocarboxylate transport across plasma and
      mitochondrial membranes. When exposed to N-methyl-D-aspartate, slices lost
      synaptic transmission and K+ homeostasis more slowly in glucose-containing
      artificial cerebrospinal fluid than in lactate-containing artificial
      cerebrospinal fluid. After N-methyl-D-aspartate exposure, slices recovered
      synaptic transmission more completely in glucose. These results suggest that
      hippocampal neurons can use glucose more effectively than lactate when energy
      demand is high. In experiments with alpha-cyano-4-hydroxycinnamate, 500 microM
      alpha-cyano-4-hydroxycinnamate caused loss of K+ homeostasis and synaptic
      transmission in hippocampal slices during normoxia. When 200 microM alpha-cyano-4
      hydroxycinnamate was used, synaptic activity and intracellular pH in slices
      decreased significantly during normoxia. These results suggest that alpha-cyano-4
      hydroxycinnamate may have blocked mitochondrial oxidative metabolism along with
      lactate transport. Thus, studies using alpha-cyano-4-hydroxycinnamate to
      demonstrate the presence of a lactate shuttle in the brain tissue may need
      reevaluation. Our findings, together with observations in the literature that (1)
      glucose is available to neurons during activation, (2) heightened energy demand
      rapidly activates glycolysis in neurons, and (3) activation of glycolysis
      suppresses lactate utilization, suggests that glucose is the primary substrate
      for neurons during neuronal activation and do not support the astrocyte-neuron
      lactate shuttle hypothesis.

PMID- 11223003
TI  - Naturalistic activation of barosensitive afferents release substance P in the
      nucleus tractus solitarius of the cat.
AB  - The role for substance P (SP) in baroreceptor transmission in the nucleus tractus
      solitarius (NTS) remains an area of active research. The purpose of the present
      study was to determine whether naturalistic activation of barosensitive afferent
      fibers in the glossopharygneal and vagus nerves release SP in the caudal NTS.
      Experiments were performed on chloralose anesthetized, artificially ventilated
      and paralyzed cats. A microdialysis probe was stereotaxically positioned
      unilaterally in the NTS. Dialysate samples were collected and SP-like
      immunoreactivity (SP-LI) was measured by radioimmunoassay. Barosensitive
      afferents were mechanically activated by inflation of a balloon catheter
      positioned in the thoracic aorta at heart level. Graded balloon inflation
      produced increases in mean arterial pressure (MAP) of 33+/-5 mmHg and 60+/-3 mmHg
      (P<0.05) and evoked proportional baroreflex decreases in heart rate of 8+/-3
      b.p.m. and 19+/-3 b.p.m. (P<0.05). This was accompanied by increases in SP-LI of
      16+/-3% and 39+/-8%, respectively (P<0.05). A positive linear relationship was
      found between changes in MAP and SP-LI (slope=1.73 fmol/microl/mmHg, r(2)=0.62)
      that was completely abolished following barodenervation. These findings provide
      evidence that naturalistic activation of pressure-sensitive afferents in the
      glossopharygneal and vagus nerves release SP in a region of the NTS that receives
      primary afferent projections from aortic, carotid sinus and cardiac receptors in
      the cat.

PMID- 11223004
TI  - Changes in EEG power spectra and behavioral states in rats exposed to the
      acetylcholinesterase inhibitor chlorpyrifos and muscarinic agonist oxotremorine.
AB  - Organophosphates (OPs) inhibit acetylcholinesterase (AChE) activity causing
      cholinergic stimulation in the central nervous system (CNS). Cholinergic systems
      are crucial in electroencephalogram (EEG) generation and regulation of behavior;
      however, little is known about how OP exposure affects the EEG and behavioral
      states. We recorded EEG, core temperature and motor activity before and after
      exposure to the OP pesticide chlorpyrifos (CHP) in adult female rats implanted
      with telemetric transmitters. The recording and reference electrodes were placed
      in the occipital and frontal bones, respectively. The animals received CHP, 25
      mg/kg, p.o., or oxotremorine (OX), 0.2 mg/kg, s.c. CHP led to a significant
      increase in delta (0.1-3.5 Hz), slow theta (4-6.5 Hz), gamma 2 (35.5-50 Hz),
      reduction in fast theta (7-8.5 Hz), alpha/sigma (9-14 Hz), beta 1 (14.5-24 Hz),
      beta 2 (24.5-30 Hz) and gamma 1 (30.5-35 Hz) powers, slowing of peak frequencies
      in 1-9 Hz range, hypothermia and decrease in motor activity. The drop in 7-14 Hz
      was associated with cholinergic suppression of sleep spindles. Changes in
      behavioral state were characterized by dramatic diminution of sleep postures and
      exploring activity and prolongation of quiet waking. There was recovery in all
      bands in spite of continued inhibition of AChE activity [44,45] in rats exposed
      to CHP. OX-induced EEG and behavioral alterations were similar to CHP except
      there was no increase in delta and the onset and recovery were more rapid. We did
      not find a correlation between the EEG and core temperature alterations. Overall,
      changes in EEG (except in delta band) and behavior following CHP were
      attributable to muscarinic stimulation. Cortical arousal together with increased
      quiet waking and decreased sleep after CHP occurred independently from inhibition
      of motor activity and lowering of core temperature.

PMID- 11223005
TI  - Increased extracellular DA and normal evoked DA release in the rat striatum after
      a partial lesion of the substantia nigra.
AB  - After injection of 6-hydroxydopamine into the lateral part of the rat substantia
      nigra, tissue dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic
      acid (HVA) were reduced in the corresponding lateral part of the ipsilateral
      caudate/putamen (CP) complex (13, 40 and 56% of controls, respectively). In this
      region, tyrosine hydroxylase (TH, the rate limiting enzyme of the DA synthesis)
      immunoautoradiography decreased by more than 80% as was the case for the binding
      of tritiated GBR12935 (a specific marker of the DA-carrier protein). In the
      medial region of the CP, only very moderate reductions of DA, DOPAC and HVA (77,
      76 and 84% of controls, respectively) were observed. In this region, TH
      immunoautoradiography and GBR12935 binding were only reduced by about 20%
      reflecting weak DA denervation. However, using in vivo voltammetry, extracellular
      basal DA levels were found to be particularly high in the medial region of CP
      complex when compared to unoperated animals (up to 235%). In the medial region,
      TH activity was also significantly increased (161%) but the electrical
      stimulation of DA fibers produced the same DA overflow in control and lesioned
      animals. From these results, it may be concluded that elevated basal DA levels in
      this region cannot be attributed to the reduced DA uptake and/or to an increased
      ability of DA neurons to release DA in response to impulse flow.

PMID- 11223007
TI  - Insulin reverses impaired acetylcholine-induced dilatation of the rat basilar
      artery during diabetes mellitus.
AB  - The goal of this study was to determine whether treatment of diabetic rats with
      insulin reverses impaired nitric oxide synthase-dependent reactivity of the
      basilar artery in vivo. We measured the diameter of the basilar artery in non
      diabetic rats, diabetic (streptozotocin; 50-60 mg/kg i.p.) rats, and diabetic
      rats treated with insulin implants in response to acetylcholine and nitroglycerin
      before and following topical application of N(G)-monomethyl-L-arginine (L-NMMA).
      Reactivity of the basilar artery was measured 2-3 months after injection of
      streptozotocin. We found that topical application of acetylcholine (1.0 and 10
      microM) produced dose-related dilatation of the basilar artery in non-diabetic
      rats, which was inhibited (>80%) by topical application of L-NMMA (10 microM). In
      diabetic rats, the magnitude of vasodilation produced by acetylcholine was
      significantly less than in non-diabetic rats. Further, topical application of L
      NMMA did not affect dilatation of the basilar artery in diabetic rats in response
      to acetylcholine. In insulin treated diabetic rats, dilatation of the basilar
      artery in response to acetylcholine was significantly greater than that observed
      in either non-diabetic or diabetic rats. In contrast, dilatation of the basilar
      artery in response to nitroglycerin was similar in insulin treated diabetic rats,
      non-diabetic rats and diabetic rats. Topical application of L-NMMA only partially
      inhibited dilatation of the basilar artery in response to acetylcholine in
      diabetic rats treated with insulin. Thus, the findings of this study suggest that
      impaired acetylcholine-induced dilatation of the basilar artery during diabetes
      mellitus can be restored by treatment with insulin. Further, it appears that the
      contribution of cellular pathways, in addition to nitric oxide synthase, may
      contribute to dilatation of the basilar artery in response to acetylcholine in
      rats treated with insulin.

PMID- 11223006
TI  - Actions of cocaine- and amphetamine-regulated transcript (CART) peptide on
      regulation of appetite and hypothalamo-pituitary axes in vitro and in vivo in
      male rats.
AB  - Cocaine- and amphetamine-regulated transcript (CART) and CART peptide are
      abundant in hypothalamic nuclei controlling anterior pituitary function.
      Intracerebroventricular (ICV) injection of CART peptide results in neuronal
      activation in the paraventricular nucleus (PVN), rich in corticotrophin-releasing
      factor (CRH) and thyrotrophin-releasing factor (TRH) immunoreactive neurons. The
      aims of this study were three-fold. Firstly, to examine the effects of CART
      peptide on hypothalamic releasing factors in vitro, secondly, to examine the
      effect of ICV injection of CART peptide on plasma pituitary hormones and finally
      to examine the effect of PVN injection of CART peptide on food intake and
      circulating pituitary hormones. CART(55-102) (100 nM) peptide significantly
      stimulated the release of CRH, TRH and neuropeptide Y from hypothalamic explants
      but significantly reduced alpha melanocyte stimulating hormone release in vitro.
      Following ICV injection of 0.2 nmol CART(55-102), a dose which significantly
      reduces food intake, plasma prolactin (PRL), growth hormone (GH) and
      adrenocorticotrophin hormone (ACTH) and corticosterone increased significantly.
      Following PVN injection of CART(55-102), food intake was significantly reduced
      only at 0.2 and 0.6 nmol. However, PVN injection of 0.02 nmol CART(55-102)
      produced a significant increase in plasma ACTH. ICV injection of CART peptide
      significantly reduces food intake. Unlike many anorexigenic peptides, there is no
      increased sensitivity to PVN injection of CART(55-102). In contrast, both ICV and
      PVN injection of CART(55-102) significantly increased plasma ACTH and release of
      hypothalamic CRH is significantly increased by CART peptide in vitro. This
      suggests that CART peptide may play a role in the control of pituitary function
      and in particular the hypothalamo-pituitary adrenal axis.

PMID- 11223008
TI  - Comparative effects of scopolamine and quinpirole on the striatal fos expression
      induced by stimulation of D(1) dopamine receptors in the rat.
AB  - Treatment of intact rats with the full D(1) dopamine agonist A-77636 induced Fos
      like immunoreactivity in the medial and, to a lesser extent, the lateral portions
      of the striatum. Pretreatment with the muscarinic antagonist scopolamine
      hydrobromide (1.5-6 mg/kg) potentiated the response to A-77636 and eliminated the
      mediolateral staining gradient seen after A-77636 alone. Similar effects were not
      produced by scopolamine methylbromide, which fails to cross the blood-brain
      barrier, demonstrating that the actions of scopolamine were centrally mediated.
      The effects of scopolamine were further compared to those of the D(2)-like
      dopamine agonist quinpirole using a factorial design in which subjects were
      pretreated with either scopolamine, quinpirole, or a combination of the two drugs
      before receiving A-77636. Pretreatment with either scopolamine or quinpirole
      increased staining in the lateral striatum, but the combination of the two drugs
      was no more effective than was quinpirole alone. Pretreatment with quinpirole,
      but not scopolamine, resulted in a markedly "patchy" pattern of staining and
      actually suppressed staining in the region between patches in the medial
      striatum. These findings demonstrate that there are both differences and
      similarities between the effects of scopolamine and quinpirole on D(1) agonist
      induced Fos expression and suggest that although inhibition of cholinergic
      neurons may be one of the mechanisms through which the effects of quinpirole are
      produced, other factors must also contribute.

PMID- 11223009
TI  - The estrous cycle affects pseudorabies virus (PRV) infection of the CNS.
AB  - Previous work had suggested that mucosal immunity may be affected by the stage of
      the estrous cycle. Here, susceptibility to a neurotropic virus infection at
      different stages of the estrous cycle was assessed in a rodent model after direct
      injection of the virus into visceral organs. In the first two experiments, female
      Sprague-Dawley rats were infected with pseudorabies virus (PRV, Bartha's K
      strain) by injection into either the cervix or the kidney after monitoring their
      estrous cycle. After either 4- or 5-day survival period post-infection, the rats
      were euthanized by transcardially perfusion and peripheral and central nervous
      system tissues were removed for immunocytochemical staining. The number of
      infected neurons was counted in various regions. Statistical analysis revealed
      that: (1) the number of infected cells in the sympathetic or parasympathetic
      ganglion, or the dorsal root ganglia was not affected regardless of the stage of
      the estrous cycle after cervix injection with PRV; (2) in contrast, the number of
      infected neurons in the spinal cord was affected significantly by the stage of
      the estrous cycle during viral infection of the cervix; (3) after kidney
      infection, the number of infected neurons found within the spinal cord or dorsal
      root ganglia varied significantly across the estrous cycle. In both cases,
      animals infected in proestrus or estrus had fewer infected neurons than animals
      infected in diestrus I or diestrus II (proestrous and estrous animals had less
      than 20% of infected cells found in diestrus I or diestrus II rats). In the third
      experiment, older, persistent estrous or persistent diestrous rats were infected
      by kidney injection and given a 4-day survival period, prior to virus isolation
      from lower thoracic spinal cord. Animals in persistent estrous had significantly
      less virus per gram of tissue than the persistent diestrous rats. These data
      suggest that the CNS of animals in proestrus or estrus is less susceptible to PRV
      infection compared to animals in either diestrus I or diestrus II. Because
      estrogen replacement therapy is known to restore some immune functions during
      reproductive ageing, it is speculated that plasma estrogen levels modulate the
      central nervous system's susceptibility to viral infections.

PMID- 11223010
TI  - Change in gene expression in facial nerve nuclei and the effect of superoxide
      dismutase in a rat model of ischemic facial paralysis.
AB  - Peripheral nerve injury induces changes in gene expressions of a variety of
      neuroactive substances in cell somata, which may have roles in the adaptive
      response to the injury, neuronal survival, growth and regeneration. In this
      study, we designed a rat model of ischemic peripheral facial paralysis with a
      selective embolization technique, and observed mRNA expression of calcitonin gene
      related peptide (CGRP), c-jun, and growth associated protein (GAP)-43 in facial
      nerve nuclei using in situ hybridization histochemistry. The rats were
      demonstrated to have a transient facial paralysis consistently, and thus this
      method was regarded as a model of minor peripheral nerve injury. The mRNA of
      CGRP, c-jun and GAP-43 showed a distinct pattern of induction and time course of
      increase after the ischemic nerve injury. The results suggest that the small
      injury to the peripheral nerve was able to induce changes in mRNA expression in
      the cell body of motoneurons. We also investigated the protective effect of
      superoxide dismutase (SOD), which is a free radical-scavenging enzyme involved in
      cellular antioxidant defenses. The SOD treatment clearly alleviated the
      behavioral impairment and decreased the CGRP mRNA expression at 3rd day after
      injury. These data suggest that a free radical generated by the ischemia may be
      partially responsible for ischemic nerve damage and the change in gene expression
      in motoneurons.

PMID- 11223011
TI  - TNFalpha reduces glutamate induced intracellular Ca(2+) increase in cultured
      cortical astrocytes.
AB  - The proinflammatory cytokine TNFalpha is locally released during various
      inflammatory CNS diseases and high cerebrospinal fluid (CSF) titers of TNFalpha
      were found in meningitis patients. We know from previous studies that TNFalpha
      also depolarizes astrocytes by reducing their inwardly rectifying K+ currents. We
      have now investigated the effect of TNFalpha on the glutamate induced
      intracellular Ca2+ increase in astrocytes, a process which seems to be involved
      in glial mediated modulation of neuronal synaptic transmisssion. Incubation with
      TNFalpha (50-1000 U/ml for 60 min) reduces the glutamate induced intracellular
      Ca2+ increase in astrocytes but not in neurons and this seems to be a phenomenon
      secondary to the TNFalpha induced depolarization. While other proinflammatory
      cytokines (interleukin 1beta, IL-2, IL-6) did not interfere with the astrocytic
      glutamate response, incubation in CSF from septic meningitis patients (CSF-SM)
      also reduced the glutamate induced intracellular Ca2+ increase. The application
      of a neutralizing anti-TNFalpha antibody to the CSF-SM prior to cell incubation
      partially restored the glutamate response. Our data suggest that inflammatory
      molecules such as TNFalpha impair astrocytes' response to glutamate and this may
      indirectly affect neuronal synaptic transmission.

PMID- 11223012
TI  - Immunohistochemical localization of interleukin-2 and its receptor subunits
      alpha, beta and gamma in the main olfactory bulb of the rat.
AB  - Endogenous interleukin-2 (IL-2) was found in the adult rat brain, however, it has
      not been reported whether this cytokine is present in the olfactory bulb.
      Immunohistochemical techniques were used to examine the cellular localization of
      IL-2 and its receptor subunits in the main olfactory bulb of the rat. Strong IL-2
      immunoreactivity was localized in glial cells, specifically in the olfactory
      nerve layer, glomerular layer and external plexiform layer. IL-2 mRNA was
      detected in the olfactory bulb by RT-PCR. All three IL-2 receptor subunits also
      showed distinct laminar distributions. The IL-2Ralpha and IL-2Rbeta
      immunoreactivity was found both in neurons and glial cells, whereas IL-2Rgamma
      imunoreactivity was found in glial cells, and thus resembled IL-2 immunostaining.
      The present results demonstrated a wide distribution of IL-2 and its receptor
      subunits in the main olfactory bulb of the rat, suggesting that IL-2 might play a
      role in the olfactory function through autocrine or paracrine pathways. The
      exclusive high expression of IL-2 in glial cells in distinct laminar structures,
      where neuron-glia interactions are closely associated with olfactory nerve
      regeneration, imply that IL-2 might be involved in the process of nerve
      regeneration in the olfactory bulb.

PMID- 11223013
TI  - GABA immunoreactivity in the olfactory bulbs of the adult sea lamprey Petromyzon
      marinus L.
AB  - The distribution of gamma-aminobutyric acid (GABA) immunoreactivity in the
      olfactory bulbs of the adult sea lamprey was studied using an antibody against
      this transmitter. Five types of GABA-immunoreactive (GABAir) cells were observed.
      Medium-sized GABAir cells (periglomerular cells) were located around the
      olfactory glomeruli and occasionally within them. In the inner cellular layer of
      the bulbs and around the olfactory ventricles, two types of GABAir perikarya were
      present: some medium-sized GABAir cells and numerous small GABAir cells
      (granules). In the walls of the olfactory ventricle, some medium-sized GABAir
      cells of cerebrospinal fluid-contacting type were observed. At the entrance of
      the olfactory nerves, medium-sized GABAir bipolar cells were present, mostly
      located between the olfactory nerve and the glomerular layer or close to the
      meninges, but some in the intracranial portion of the olfactory nerve. GABAir
      processes were present in all layers of the olfactory bulb. In addition there
      were also GABAir cells in the dorsal interbulbar commissure. The distribution of
      GABA observed in the olfactory system of lampreys indicates that this transmitter
      plays a major role in the modulation of bulbar circuits. The presence of granular
      and periglomerular cells in lampreys indicates that these two intrinsic GABAergic
      neurons of the olfactory bulbs are shared by most vertebrates, although lampreys
      have additional GABAir cell types.

PMID- 11223014
TI  - Two point mutations in mitochondrial DNA of cytochrome c oxidase coexist with
      normal mtDNA in a patient with Alzheimer's disease.
AB  - The mitochondrial cytochrome c oxidase (CO) gene sequence was determined on a
      patient with Alzheimer's disease (AD). Compared to the standard Cambridge
      sequence to identify base changes,two missense mutations were found in the
      patient with AD. The mutations were a G to T transition at np 8206 and an A to T
      transition at np 8224. The np 8206 mutation changed a Met to an Ile and np 8224
      mutation changed a Leu to a Phe. The normal bases and the mutations of
      mitochondrial DNA (mtDNA) coexist in the patient. Further studies will be
      required to demonstrate the role of the point mutations of mitochondrial DNA in
      the pathogenesis of Alzheimer's disease.

PMID- 11223015
TI  - Anti-nociceptive effect of neuropeptide Y in periaqueductal grey in rats with
      inflammation.
AB  - Experimental inflammation was induced by subcutaneous injection of carrageenan
      into the left hindpaw of rats. Intra-periaqueductal grey (PAG) injection of 0.02
      or 0.1 nmol of neuropeptide Y (NPY), but not 0.004 nmol, induced significant
      increases in hindpaw withdrawal latency (HWL) to thermal and mechanical
      stimulation in rats with inflammation. Furthermore, the anti-nociceptive effect
      of NPY was blocked partly by following intra-PAG injection of the Y1 receptor
      antagonist NPY28-36. The results demonstrated that NPY plays an anti-nociceptive
      role in PAG in rats with inflammation, in which Y1 receptor is involved.

PMID- 11223016
TI  - Does CDP-choline modulate phospholipase activities after transient forebrain
      ischemia?
AB  - Ten min forebrain ischemia/1-day reperfusion resulted in significant decreases in
      total phosphatidylcholine (PtdCho), phosphatidylinositol (PtdIns), and
      cardiolipin in gerbil hippocampus. CDP-choline restored cardiolipin levels,
      arachidonic acid content of PtdCho, partially but significantly restored total
      PtdCho, and had no effect on PtdIns. These data suggest that CDP-choline
      prevented the activation of phospholipase A(2) (rather than inhibiting
      phospholipase A(2) activity) but did not affect activities of PtdCho
      phospholipases C and/or D, or phosphoinositide-phospholipase C. CDP-choline also
      provided significant protection for hippocampal CA(1) neurons.

PMID- 11223017
TI  - Responses of small- and large-field bipolar cells to GABA and glycine.
AB  - Morphologically distinct subtypes of retinal bipolar cells transmit information
      along parallel pathways to convey different aspects of the visual scene, but the
      synaptic mechanisms that regulate signal transmission are largely unknown. The
      all-rod retina of skate provides a comparatively simple system in which to
      correlate bipolar cell morphology with responses to the inhibitory
      neurotransmitters GABA and glycine. Two subtypes of bipolar cells can be
      identified when isolated in culture: large-field bipolar cells with extensive
      dendritic arbors, and small-field bipolar cells with one or two dendritic
      branches. Under voltage-clamp, glycine elicited significant current responses
      from small-field cells, but not from large-field bipolar cells. Although all
      bipolar cells displayed GABA-activated chloride currents mediated by both GABA(A)
      and GABA(C) receptors, the small-field bipolar cells showed a significantly
      greater contribution from GABA(A) receptors. The results of the present study
      reveal for the first time that the relative expression of the two classes of GABA
      receptor on each bipolar cell type correlates with cell morphology and the
      presence of the glycine receptor.

PMID- 11223018
TI  - COMT-dependent protection of dopaminergic neurons by methionine, dimethionine and
      S-adenosylmethionine (SAM) against L-dopa toxicity in vitro.
AB  - L-dopa may be toxic to dopamine neurons, possibly due to catechol-autoxidation.
      Catechols are O-methylated by catechol-O-methyltransferase (COMT) in a SAM
      consuming reaction, preventing the initiation of catechol autoxidation. We
      hypothesized that SAM or SAM-precursors ameliorate L-dopa neurotoxicity, in a
      COMT-dependent fashion. We tested this hypothesis in primary mesencephalic
      cultures by adding 200 microM L-dopa with 2 mM methionine or 1 mM dimethionine or
      0.5 mM SAM with or without 0.2 microM of the COMT-inhibitor 2', 5'
      dinitrocatechol (OR 486). L-dopa was found to be neurotoxic as the surviving
      neurons had fewer and shorter processes. Methionine, dimethionine and SAM all
      protected DA neurons against damaged induced by L-dopa. The COMT inhibitor
      dinitrocatechol (DNC) completely abolished the protective effect against L-dopa
      toxicity. We conclude that supplementation with methionine, dimethionine or SAM
      ameliorates L-dopa neurotoxicity to dopamine neurons, while inhibition of COMT
      may aggravate or unmask L-dopa neurotoxicity.

PMID- 11223019
TI  - Neostriatal stimulation activates tongue-protruder muscle, but not tongue
      retractor or facial muscles: an electrical and chemical microstimulation study in
      rats.
AB  - Whether electrical microstimulation of a rat's striatal jaw region (SJR) in fact
      induced tongue or facial muscle activity in addition to jaw muscle activity was
      tested. Microstimulation of SJR-evoked EMG activity in a jaw-opener (anterior
      digastricus) and tongue-protruder (genioglossus). No activity was evoked in jaw
      closers (temporalis or masseter), tongue-retractor (hyoglossus) or in facial
      muscles. In addition, the EMG effect could still be induced after extensive
      ablation of the neocortex; it was reproduced by microinjection of 50 mM kainic
      acid into SJR. The effective sites were histologically localized to a small
      central striatal region adjoining the anterior commissure. These findings may be
      of considerable value in understanding the striatal mechanism of orolingual
      dyskinesia involving involuntary jaw and tongue movements.

PMID- 11223020
TI  - Acidic pH promotes the formation of toxic fibrils from beta-amyloid peptide.
AB  - Beta-amyloid (Abeta) peptides, the major component of senile plaques in brains of
      patients with Alzheimer's disease (AD), were found in the low pH organelles (i.e.
      endosome/lysosome) of cultured neuronal cells. Since acidic pH values have been
      shown to promote the self-assembly of Abetas, which seems to be a prerequisite
      for their neuropathogenicity, elucidating the aggregation behavior of Abetas in
      acidic environments and their subsequent effects on neuronal cells may be crucial
      for understanding the neurodegenerative process of AD. In this study, the extent
      and rate of aggregation of Abeta(1-42) peptides at pH values of 5.8 and 7.4, as
      well as the structure and neurotoxic effects of these aggregates, were examined.
      We showed that Abeta(1-42) peptides formed large and complex fibrils much more
      efficiently at acidic rather than neutral pH. Furthermore, only the pH 5.8 Abeta
      aggregates induced significant apoptotic death of PC12 cells, as indicated by a
      decrease in 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT)
      reduction and an increase in phosphatidylserine externalization. Taken together,
      our results suggest that the Abetas present in the acidic organelles may form
      neurotoxic fibrils more easily than those in the neutral cellular compartments.

PMID- 11223021
TI  - Spinal taurine levels are increased 7 and 30 days following methylprednisolone
      treatment of spinal cord injury in rats.
AB  - The amino acid taurine serves many functions in the nervous system serving as
      inhibitory neurotransmitter/neuromodulator, neurotrophin, antioxidant, and
      osmolyte. Taurine levels are increased following brain injury and glucocorticoid
      administration. Thus, the purpose of this study was to examine spinal taurine
      concentrations following spinal cord injury (SCI) and methylprednisolone (MP)
      treatment of SCI. A total of 44 adult male Sprague-Dawley rats were divided into
      control and lesion groups. Control rats received a T6 vertebral laminectomy while
      lesioned rats received a laminectomy followed by complete spinal transection.
      Half of the animals in each group received MP intravenously following sham
      operation or SCI. Rats survived for 7 or 30 days and concentrations of taurine in
      spinal gray and white matter, in spinal segments both near and distant from the
      injury epicenter, were resolved by HPLC analysis. Taurine levels were increased 7
      and 30 days following transection in spinal segments immediately adjacent to the
      lesion and were further elevated by MP treatment. No increases were seen in far
      rostral/caudal segments, and MP treatment alone had no effect on spinal taurine
      levels. These findings demonstrate that spinal injury results in increased
      taurine concentrations in spinal segments undergoing the greatest degree of
      cellular reactivity and tissue reorganization and that MP therapy potentiates
      these increases. These findings are significant in that they further characterize
      the effects of acute MP therapy in spinal tissue. Since taurine is thought to be
      involved in neuroprotection and/or regeneration following injury, the
      potentiation of taurine levels by MP treatment may relate to its therapeutic
      properties.

PMID- 11223024
TI  - Making decisions in G1. Proceedings of a workshop. Rome, Italy.

PMID- 11223022
TI  - Stress response to hypoxia in gerbil brain: HO-1 and Mn SOD expression and glial
      activation.
AB  - Hypoxic preconditioning has been shown to induce neuroprotection against a
      subsequent damaging insult. In order to study the underlying molecular and
      cellular mechanisms of hypoxic preconditioning, we investigated, in gerbil
      hippocampus, the effects in vivo of transient exposure to hypoxia (4% O(2) for 6
      min followed by either 48 h or 7 days of reoxygenation) (i) on the induction of
      72 kDa heat shock protein (HSP72), heme oxygenase-1 (HO-1) and manganese
      superoxide dismutase (Mn SOD) as assessed by Western immunoblotting and (ii) on
      the astroglial and microglial activation as detected by both immunohistochemistry
      and Western immunoblotting for GFAP, and histochemistry for isolectin B4,
      respectively. Our data show that, although hypoxia and subsequent reoxygenation
      led to neither neuronal damage nor HSP72 induction in gerbil hippocampus, it
      induced a progressive and sustained expression of HO-1 and Mn SOD. As expected
      from the absence of neuronal death, hypoxia was not associated with microglial
      activation but led to a significant astrocytic activation. These findings
      demonstrate that transient hypoxia enhances the antioxidative enzymatic defenses
      of the brain, which are susceptible to increased tolerance against a subsequent
      damaging insult.

PMID- 11223025
TI  - Growth factor-dependent signaling and cell cycle progression.
AB  - There are three central ideas contained within this review. Firstly, growth
      factor-stimulated signaling is not restricted to a 30-60 min window, but occurs
      at a much later time as well. Secondly, the second wave of signaling overlaps
      temporally with the cell cycle program and may be directly responsible for
      engaging it. Thirdly, the G1 to S interval appears to encompass two distinct
      phases of the cell cycle, during which the coordinated activation of distinct
      sets of signaling enzymes drives cell cycle progression. Each of these concepts
      is likely to initiate new investigation and hence provide additional insight into
      the fundamental question of how growth factors drive cell proliferation.

PMID- 11223027
TI  - Ras-dependent cell cycle commitment during G2 phase.
AB  - Synchronization used to study cell cycle progression may change the
      characteristics of rapidly proliferating cells. By combining time-lapse,
      quantitative fluorescent microscopy and microinjection, we have established a
      method to analyze the cell cycle progression of individual cells without
      synchronization. This new approach revealed that rapidly growing NIH3T3 cells
      make a Ras-dependent commitment for completion of the next cell cycle while they
      are in G2 phase of the preceding cell cycle. Thus, Ras activity during G2 phase
      induces cyclin D1 expression. This expression continues through the next G1 phase
      even in the absence of Ras activity, and drives cells into S phase.

PMID- 11223026
TI  - Pathways governing G1/S transition and their response to DNA damage.
AB  - The ability to self-replicate is a fundamental feature of life, reflected at the
      cellular level by a highly regulated process initiated in G1 phase via commitment
      to a round of DNA replication and cell division. Here we briefly highlight recent
      advances in understanding the molecular pathways which govern the decision of
      mammalian somatic cells to enter S phase, and the so-called cell cycle
      checkpoints which guard the G1/S transition and S phase progression against
      potentially deleterious effects of genotoxic stress. Particular emphasis is put
      on the emerging parallel yet cooperative pathways of retinoblastoma protein (pRB)
      E2F and Myc, their convergence to control the activity of the cyclin-dependent
      kinase 2 (Cdk2) at the G1/S boundary, as well as the two waves of checkpoint
      responses at G1/S: the rapid pathway(s) leading to Cdc25A degradation, and the
      delayed p53-p21 cascade, both silencing the Cdk2 activity upon DNA damage.

PMID- 11223028
TI  - Negative regulation of receptor tyrosine kinase signals.
AB  - In Metazoans a number of cellular functions are controlled by receptor tyrosine
      kinases (RTKs) during development and in postnatal life. The execution of these
      programs requires that signals of adequate strength are delivered for the
      appropriate time within precise spatial boundaries. Several RTK inhibitors have
      been identified in invertebrate and mammalian organisms. Because they are
      involved in tuning and termination of receptor signals, negative regulators of
      RTK activity fulfill a fundamental function in the control of receptor signaling.

PMID- 11223029
TI  - Molecular mechanisms underlying endocytosis and sorting of ErbB receptor tyrosine
      kinases.
AB  - The major process that regulates the amplitude and kinetics of signal
      transduction by tyrosine kinase receptors is endocytic removal of active ligand
      receptor complexes from the cell surface, and their subsequent sorting to
      degradation or to recycling. Using the ErbB family of receptor tyrosine kinases
      we exemplify the diversity of the down regulation process, and concentrate on two
      sorting steps whose molecular details are emerging. These are the Eps15-mediated
      sorting to clathrin-coated regions of the plasma membrane and the c-Cbl-mediated
      targeting of receptors to lysosomal degradation. Like in yeast cells, sorting
      involves not only protein phosphorylation but also conjugation of ubiquitin
      molecules. The involvement of other molecules is reviewed and recent observations
      that challenge the negative regulatory role of endocytosis are described.
      Finally, we discuss the relevance of receptor down regulation to cancer therapy.

PMID- 11223030
TI  - Making decisions through Myc.
AB  - c-Myc is a transcriptional regulator involved in carcinogenesis through its role
      in growth control and cell cycle progression. Here we attempt to relate its role
      in stimulating the G1-S transition to the ability to affect functioning of key
      cell cycle regulators, and we focus on how its property of modulating
      transcription of a wide range of target genes could explain its capacity to
      affect multiple pathways leading to proliferation, apoptosis, growth, and
      transformation.

PMID- 11223031
TI  - From p63 to p53 across p73.
AB  - Most genes are members of a family. It is generally believed that a gene family
      derives from an ancestral gene by duplication and divergence. The tumor
      suppressor p53 was a striking exception to this established rule. However, two
      new p53 homologs, p63 and p73, have recently been described [1-6]. At the
      sequence level, p63 and p73 are more similar to each other than each is to p53,
      suggesting the possibility that the ancestral gene is a gene resembling p63/p73,
      while p53 is phylogenetically younger [1,2].The complexity of the family has also
      been enriched by the alternatively spliced forms of p63 and p73, which give rise
      to a complex network of proteins involved in the control of cell proliferation,
      apoptosis and development [1,2,4,7-9]. In this review we will mainly focus on
      similarities and differences as well as relationships among p63, p73 and p53.

PMID- 11223032
TI  - Regulation of MyoD function in the dividing myoblast.
AB  - Proliferating myoblasts express MyoD, yet no phenotypic markers are activated as
      long as mitogen levels are sufficient to keep the cells dividing. Depending upon
      mitogen levels, a decision is made in G1 that commits the myoblast to either
      continue to divide or to exit from the cell cycle and activate terminal
      differentiation. Ectopic expression of MyoD under the control of the RSV or CMV
      promoters causes 10T1/2 cells to rapidly exit the cell cycle and differentiate as
      single myocytes, even in growth medium, whereas expression of MyoD under the
      weaker SV40 promoter is compatible with proliferation. Co-expression of MyoD and
      cyclin D1, but not cyclins A, B, E or D3, blocks transactivation of a MyoD
      responsive reporter. Similarly, transfection of myoblasts with the cyclin
      dependent kinase (cdk) inhibitors p16 and p21 supports some muscle-specific gene
      expression even in growth medium. Taken altogether, these results suggest cell
      cycle progression negatively regulates myocyte differentiation, possibly through
      a mechanism involving the D1 responsive cdks. We review evidence coupling growth
      status, the cell cycle and myogenesis. We describe a novel mitogen-sensitive
      mechanism that involves the cyclin D1-dependent direct interaction between the G1
      cdks and MyoD in the dividing myoblast, which regulates MyoD function in a
      mitogen-sensitive manner.

PMID- 11223033
TI  - Regulation of the G1 to S transition by the ubiquitin pathway.
AB  - This year the most prestigious prize in medical sciences, the Lasker Award, has
      been presented to the three scientists who discovered the ubiquitin pathway:
      Aaron Ciechanover, Avram Hershko, and Alexander Varshavsky [Nature Med. 6 (2000)
      1073-1081]. During a time when the scientific community was focused on
      understanding how proteins were synthesized, they intently pursued the novel idea
      that cells were programmed to selectively destroy proteins. Their work led to the
      identification of an elaborate system of protein degradation targeting a myriad
      of cellular substrates. A small protein called ubiquitin is at the center of this
      process. Although the ubiquitin pathway was first described in the early 1980s,
      it has only more recently advanced to the forefront of basic research as a
      significant regulatory network within the cell. The field continues to grow as
      new ubiquitination enzymes and novel functions of this system are identified.
      Scientists are focused on elucidating the mechanisms by which cells deploy the
      ubiquitin pathway to control levels of selected proteins, such as cell cycle
      regulatory proteins, transcription factors and signaling molecules. Accelerated
      or decelerated rates of degradation of particular substrates participate in the
      genesis of many human diseases. Thus, understanding the mechanisms that confer
      specificity to the ubiquitin system will allow the development of novel
      therapeutic approaches to target aberrations in this pathway underlying
      tumorigenesis and other human pathologies.

PMID- 11223034
TI  - Functions of WW domains in the nucleus.
AB  - The WW domain is a protein module found in a wide range of signaling proteins. It
      is one of the smallest protein modules that folds as a monomer without disulfide
      bridges or cofactors. WW domains bind proteins containing short linear peptide
      motifs that are proline-rich or contain at least one proline. Although the WW
      domain was initially considered a 'cytoplasmic module', the proteins containing
      WW domains have also been localized in the cell nucleus. Moreover, these proteins
      have been documented to participate in co-activation of transcription and
      modulation of RNA polymerase II activity. The carboxy-terminal domain (CTD) of
      RNA polymerase II acts as an assembly platform for distinct WW domain-containing
      proteins that affect the function of the RNA polymerase II. The formation of
      complexes between CTD and WW domain-containing proteins is regulated by
      phosphorylation of the CTD. Since the CTD sequence is highly repetitive and a
      target of several post-translational modifications and conformational changes, it
      presents a unique structure capable of enormous molecular diversity. The WW
      domain has been implicated in several human diseases including Alzheimer's
      disease. The WW domain-containing iso-prolyl isomerase named Pin1, a protein
      known to be essential for cell cycle progression, was shown to be active in
      restoration of the microtubule-binding activity of Tau, a protein of
      neurofibrillar tangles found in the brains of Alzheimer's patients. It is the WW
      domain of Pin1 that interacts directly with Tau protein. In addition, the WW
      domain-containing adapter protein FE65 was shown to regulate processing of
      Alzheimer's amyloid precursor protein. It is expected that by understanding the
      details of the WW domain-mediated protein-protein interactions, we will be able
      to illuminate numerous signaling pathways which control certain aspects of
      transcription and cell cycle.

PMID- 11223035
TI  - Downregulation of MDM2 stabilizes p53 by inhibiting p53 ubiquitination in
      response to specific alkylating agents.
AB  - p53 is stabilized in response to DNA damaging stress. This stabilization is
      thought to result from phosphorylation in the N-terminus of p53, which inhibits
      p53:MDM2 binding, and prevents MDM2 from promoting p53 ubiquitination. In this
      report, the DNA alkylating agents mitomycin C (MMC) and methylmethane sulfonate
      (MMS), as well as UV radiation, stabilized p53 in a manner independent of
      phosphorylation in p53 N-terminus. This stabilization coincided with decreased
      levels of MDM2 mRNA and protein, and a corresponding decrease in p53
      ubiquitination. Importantly, MDM2 overexpression inhibited the stabilization of
      p53 and decrease in ubiquitination following MMC, MMS, and UV treatment. This
      indicates that downregulation of MDM2 contributes to the stabilization of p53 in
      response to these agents.

PMID- 11223037
TI  - Editorial.

PMID- 11223036
TI  - MDM2 and MDMX can interact differently with ARF and members of the p53 family.
AB  - Members of the p53 family of transcription factors have essential roles in tumor
      suppression and in development. MDM2 is an essential regulator of p53 that can
      inhibit the transcriptional activity of p53, shuttle p53 out of the nucleus, and
      target p53 for ubiquitination-mediated degradation. Little is known about the
      interaction and selectivity of different members of the p53 family (p53, p63, and
      p73) and the MDM2 family (MDM2 and MDMX). Here we show that the transcriptional
      activities of p53 and p73, but not that of p63, were inhibited by both MDM2 and
      MDMX. Consistent with these, we found that MDMX can physically interact with p53
      and p73, but not with p63. Moreover, ectopically expressed MDM2 and MDMX could
      induce alterations in the subcellular localization of p73, but did not affect the
      subcellular localization of p53 and p63. Finally, we demonstrate that while ARF
      can interact with MDM2 and inhibit the regulation of p53 by MDM2, no interaction
      was found between ARF and MDMX. These data reveal that significant differences
      and selectivity exist between the regulation of different members of the p53
      family by MDM2 and MDMX.

PMID- 11223038
TI  - Increases in fines and driver licence withdrawal have effectively reduced
      immediate deaths from trauma on Brazilian roads: first-year report on the new
      traffic code.
AB  - Road accidents are a major cause of death in Brazil, with rates increasing
      steadily for years. Our objective here is to report the impact of the new
      Brazilian Traffic Code, introduced in 1998. Its main new features include a large
      increase in fines and a rigid penalty scoring system that leads to driver license
      withdrawal. Speed limits have actually been raised on many roads, but adherence
      to the rules has been monitored more closely. We compare the incidence of injured
      patients and immediate deaths in road accidents and emergency room admissions to
      a level I trauma centre in downtown Sao Paulo between January and December 1998
      with corresponding data from between January and December 1997. There was an
      overall 21.3% reduction in the number of accidents and a 24.7% reduction in
      immediate deaths, saving 5962 lives on Brazilian highways. Tickets issued fell by
      49.5% (601977 during 1997 to 304785 during 1998). Motor vehicle accident-related
      emergency room admissions decreased by 33.2%. We conclude that very costly
      tickets and threatened driver licences have proved very effective in decreasing
      immediate deaths from trauma. Further advances in educational programmes
      associated with road and vehicle safety measures are likely to provide the much
      needed further reduction in the still high trauma mortality on Brazilian roads
      and streets.

PMID- 11223039
TI  - Ultrasound detection of blunt splenic injury.
AB  - The purpose of this study was to determine the sensitivity of emergency
      ultrasound (US) for the detection of blunt splenic injury (BSI), and to describe
      sonographic parenchymal patterns. Over 3 years, 2138 emergency US were performed,
      and 162 patients had BSI. CT was performed for 76 patients, and there were 86
      laparotomies. Seventy patients (43%) had concomitant intraabdominal injuries.
      Ultrasound detected free fluid in 109 patients (67%), and parenchymal injury in
      31 patients (19%). There were 48 false negative US (30%). Sonographic patterns
      included a diffuse heterogeneous appearance, hyperechoic and hypoechoic
      perisplenic crescents, and discrete hypoechoic or hyperechoic areas within the
      spleen. Overall sensitivity of US for detection of BSI was 69%, but was 86% for
      grade III or higher injuries. Ultrasound is most sensitive for the detection of
      grade III or higher BSI based on the presence of haemoperitoneum. Ultrasound may
      also identify BSI on the basis of parenchymal abnormality, with a diffuse
      heterogeneous pattern most commonly encountered. Sonographic evaluation for both
      free fluid and parenchymal injury improves sensitivity of US.

PMID- 11223040
TI  - Abdominal trauma due to road traffic accidents in Qatar.
AB  - OBJECTIVES: To measure the incidence and severity of abdominal trauma due to road
      traffic accidents (RTA) in Qatar. PATIENT AND METHODS: Retrospective analysis of
      all patients admitted with documented abdominal trauma to the only acute General
      Hospital in the state of Qatar in the period 1991-1995. RESULTS: In the 5-year
      period, 3744 patients were admitted following an RTA. Of these, 667 (17.8%) were
      admitted to the surgical intensive care unit (SICU) and 84 patients had abdominal
      injuries, constituting 0.45% of total number and 12.6% of patients admitted to
      SICU. Twenty-one (25%) of patients with abdominal trauma died. However, only nine
      patients died from the abdominal injury. Eight patients died due to hepatic
      injury and one patient due to splenic injury.

PMID- 11223041
TI  - Outcome in fracture healing: a review.
AB  - This editorial reviews outcome measures in fracture healing. Individually
      radiological and clinical methods are inaccurate, but together provide a good
      indicator in clinical practice when a fracture has healed. Other quantitative
      methods are not practical. Vibrational analysis of fracture healing is complex
      and limited to research at present. Indirect fracture stiffness measurement is
      possible and has been used in clinical trials. Pin loosening reduces accuracy.
      The measurement of direct fracture stiffness has been validated and using this a
      decrease in re-fracture rate and a reduction of time to independent weight
      bearing (on average 3 weeks) was found. The system is accurate and simple to use
      in the clinical setting and allows the rate of healing to be monitored in
      fractures. Studies using poor outcome measures should be interpreted with care.
      The study of healing fractures is no exception.

PMID- 11223042
TI  - The results of internal fixation of three- and four-part proximal humeral
      fractures with the Polarus nail.
AB  - Twenty-three patients with acute displaced three- and four-part fractures of the
      proximal humerus, including seven patients with associated shaft involvement,
      were treated with the Polarus intramedullary interlocking nail using a closed
      technique. At the 1-year follow up, the median Neer scores were 89 and 60 for the
      three- and four-part fractures, respectively. Three patients (13%), all of whom
      were in the four-part group, continued to have significant pain at final review.
      We found the implant to be extremely satisfactory and particularly useful in the
      treatment of combined neck and shaft fractures of the humerus.

PMID- 11223043
TI  - Injuries of the pelvic ring in road traffic accidents: a medical and technical
      analysis.
AB  - Between 1985 and 1995, 9380 traffic accidents occurring in the area of Hannover,
      Germany, were analysed; 12428 individuals had been injured and 387 (3.1%) had
      sustained a pelvic-ring injury (AIS(PELVIS)>2). In 131 cases (34%), the injuries
      were further classified (Pennal and Tile) and a technical reconstruction made of
      the accident: 52% were type A, 27% type B and 21% type C injuries; 46% were in
      cars, 12% on motorised two-wheelers, 10% on bicycles and 1% in utility vehicles;
      31% were pedestrians. Pelvic-ring injuries occurred in restrained vehicle
      occupants in accidents with a (delta)V of more than 30 km/h, whereas they
      occurred in a considerable proportion of unrestrained vehicle occupants,
      pedestrians and bicyclists at lower (delta)V or collision speed. The percentage
      of B- and C-type injuries increased in crashes with higher (delta)v or collision
      speed. In addition to further improvements of the passive safety, lower collision
      speeds or (delta)V would reduce or prevent pelvic-ring injuries. Due to the small
      number of occupants protected by airbags in this study, their protective effect
      for the pelvis could not be assessed. The reconstruction of pelvic-ring injury
      mechanism in traffic accidents is possible when technical and medical factors are
      considered.

PMID- 11223044
TI  - Clinical experience of patellar fracture fixation using metal wire or non
      absorbable polyester--a study of 37 cases.
AB  - The results of patellar fracture fixation using metal wire and non-absorbable
      polyester (5 Ethibond) are presented. In group 1 (21 cases), the standard "AO"
      technique using stainless steel wire was used, and in group 2 (16 cases) we used
      5 Ethibond. Patients were assigned to the two groups on surgeon preference. Post
      operative management in the two groups was similar, with patients being allowed
      to mobilise as comfort allowed, under the supervision of the physiotherapists.
      All patients were followed-up until union of the fractures or until further
      surgical intervention was carried out. At a mean of 2 years and 6 months (range 1
      4 years), we reviewed the notes and X-rays of all 37 cases. In group 2 there were
      no cases of infection but there were three cases of post-operative infections in
      group 1. Re-operation rate was 6/21 (38%) in group 1 and 1/6 (6%) in group 2.
      Therefore, the relative risk of re-operation in the metal group is six times that
      in the non-absorbable polyester group. The risk of infection in the metal group
      is also higher. These have implication on patient morbidity associated with the
      operative treatment of patellar fractures. Non-absorbable polyester appears to
      compare favourably with the use of metallic wire to fix patellar fractures.

PMID- 11223045
TI  - Initial rotational stability of distal tibial fractures nailed without proximal
      locking: the importance of fracture type and degree of cortical contact.
AB  - Although distally locked (dynamic) nailing is generally recommended for fractures
      below the isthmus of the tibia in the presence of adequate proximal nail-bone
      contact, rotational stability in the above situation appears to be a major
      concern and can increase the risk of malunion. However, there is no published
      experimental evidence to quantify this mechanical parameter or to relate factors
      such as the fracture pattern with the final clinical outcome. This in-vitro
      biomechanical experimental study was set out to measure the initial rotational
      stability of dynamically nailed fractures of the distal tibial diaphysis. Using a
      composite tibial model, three non-comminuted types (spiral, oblique and
      transverse) and various comminuted patterns (comminution, 0-85%) of dynamically
      nailed fractures of the distal tibial diaphysis were tested. Using a special rig
      to simultaneously apply axial and torsional loading measurements of torsional
      stiffness and the previously described "spring-back angle" were carried out. Our
      results showed that in terms of torsional stiffness and the "spring-back" angle
      oblique fractures are the most stable followed by transverse and spiral
      fractures. Furthermore, when testing of the above parameters against the degree
      of comminution was carried out, a significant reduction of rotational stability
      was evident with comminution of 50% or above. It is concluded that oblique
      fractures of the distal tibial third that can be reduced with at least 50%
      cortical apposition present the optimal rotational stability following dynamic
      nailing.

PMID- 11223046
TI  - Arthrodesis after osteosynthesis and infection of the ankle joint.
AB  - Nineteen patients with a severely infected ankle joint after previous
      osteosynthesis were treated with arthrodesis in our institution. Their notes and
      X-rays were reviewed. Goals of treatment were eradication of infection by
      aggressive debridement of infected tissues, obtaining adequate soft-tissue
      coverage, preservation/restoration of bonelength, and finally consolidation of
      the arthrodesis. Thirteen men and six women were treated, with a median age of 46
      (17-69) years. Arthrodesis took place after a median of 6 months (0.5-40) post
      accident, and after one to six earlier operative procedures. Primarily there had
      been four bimalleolar, five trimalleolar and ten pilon tibial fractures. Fifteen
      fractures were open with severe soft tissue damage. Seven free muscle transfers
      were performed, and ten cancellous bone graftings. Finally 29 attempts at
      arthrodesis were performed. Ultimately we had to perform two amputations. After a
      mean follow up of 3.5 years, one patient has an aseptic but asymptomatic
      pseudarthrosis, for which no further surgery is scheduled. Sixteen extremities
      are free from infection while full weightbearing is possible. The limb
      threatening problem of deep infection after osteosynthesis of an ankle fracture
      can be resolved by consistent but prolonged treatment. After successful
      arthrodesis a weightbearing extremity without infection remains in the majority
      of cases.

PMID- 11223047
TI  - Traumatic intrapericardial diaphragmatic hernia: case report and literature
      review.
AB  - A traumatic rupture of the diaphragm, with herniation of the abdominal viscera
      into the thoracic cavity, is relatively rare, being observed in approximately 3
      7% of all abdominal or thoracic traumas [1]. Herniation into the pericardium is
      very rare [2]. We have reviewed the post-traumatic intrapericardial diaphragmatic
      hernias (TIPDH) published in the world literature within our reach and, as it was
      already stated in the review carried out by Van Loenhout et al. [3] in 1986,
      approximately one post-traumatic intrapericardial hernia is reported every year.
      The patient that we present makes case 82 of those published until October of
      1999.

PMID- 11223048
TI  - Fracture of the occipital condyle.

PMID- 11223049
TI  - A rare complication of percutaneous iliosacral screw in a vertically unstable
      pelvic disruption in a child.
AB  - The use of iliosacral screws in managing vertically unstable fractures in adults
      has been popularised and the early results are quite promising. However, the role
      and indication of this technique in paediatric patients are not clear. There has
      been a concern about its safety and risk of screw misplacement.

PMID- 11223050
TI  - Closed reduction of the traumatically dislocated hip: a new technique.
AB  - Traumatic dislocation of the hip joint without associated fracture is not common.
      It is the result of high energy transfer usually a RTA or fall from a height. It
      is a true emergency, and the joint should be relocated within 6h. Failure to do
      so increases the risk of avascular necrosis of the femoral head with resultant
      early degenerative joint disease often in an otherwise fit young patient.

PMID- 11223051
TI  - Percutaneous manipulation of an osteoarthritic hip for femoral nailing.
AB  - An increasing number of elderly patients with femoral shaft fractures also have
      coexisting osteoarthritis of the hip. This proves to be difficult both in
      fracture reduction [1] and localisation of the point of entry into the piriform
      fossa. To facilitate guide wire entry in a patient with osteoarthritis of the
      hip, considerable adduction of the hip may be required during conventional closed
      antegrade femoral nailing. We describe a technique using a Steinman pin on a T
      clamp to facilitate localisation of the piriform fossa.

PMID- 11223052
TI  - Confirmation of an intact patellar tendon in superior dislocation of the patella
      using magnetic resonance imaging.

PMID- 11223053
TI  - Isolated compartment syndrome of the tibialis anterior muscle.

PMID- 11223054
TI  - The interplay of knowledge and decision making between nurses and doctors in
      critical care.
AB  - This paper explores the complex interrelationships between knowledge and decision
      making as nurses and doctors interacted with each other in a critical care unit,
      which comprised a combined general intensive care and cardiothoracic surgical
      unit. The critical ethnographic study upon which this paper is based, involved a
      research group of six nurses who worked in the unit. Nurses differentially valued
      their knowledge, depending on the situation, experience and level of medical
      input. They were also involved in decision making based on their differential
      visibility in the process. Nurses' specialised knowledge of the critical care
      unit played a major role in influencing how they interacted during decision
      making.

PMID- 11223055
TI  - Tasmanian nurses' knowledge of pain management.
AB  - The aim of this research was to obtain information concerning knowledge of the
      pain management practices of Tasmanian nurses. We examined the knowledge of
      Tasmanian Registered Nurses in relation to pain management issues such as
      addiction, use of analgesics and the assessment of pain. In addition, we queried
      them about their satisfaction with information they had received about how to
      manage pain in both workplace programs and in their initial education. A total of
      2768 registered nurses were mailed a 29-item survey examining knowledge of pain
      management practices. One thousand and fifteen valid surveys were returned. Mean
      scores on the knowledge questions (72% correct) of the survey revealed deficits
      in knowledge. Nurses specifically lacked up-to-date knowledge concerning the
      pharmacological management of pain, but displayed a more up-to-date knowledge
      concerning the effect of patient variables on pain perception. Nurses also rated
      the information they received about pain management during workplace programs as
      poor, feeling that they acquired significantly more in-depth information during
      their initial education. The results of this study have implications for
      institutions involved in both patient pain management and pain management
      education.

PMID- 11223056
TI  - Factors influencing job valuation: a comparative study of critical care and non
      critical care nurses.
AB  - This study sought to identify the relationship between three predictor variables,
      perceived collaboration with medical staff, autonomy and independent actions and
      an outcome, the value hospital nurses placed on their work. In total 189 critical
      care and 366 non-critical care nurses completed a mailed survey. Critical care
      nurses perceived themselves to have a more collaborative relationship with the
      medical staff, described performing actions independent of medical orders more
      frequently and perceived their jobs to have more value than non-critical care
      nurses. However the latter group perceived themselves to have more autonomy in
      their work. Within both groups collaboration and autonomy were significantly, but
      weak to moderately correlated with job valuation. Simply expanding the work
      hospital nurses do is unlikely to result in nurses valuing their jobs more,
      however promoting an environment of respect and sharing between the medical and
      nursing staff and supporting nurses when they act in an autonomous fashion may
      positively influence nurses' perceptions of their work.

PMID- 11223058
TI  - Spiritual resources of Chinese immigrants with breast cancer in the USA.
AB  - A synthesis of ethnographic and phenomenological research approaches was used to
      investigate spiritual resource as the lived experience of Chinese immigrants with
      breast cancer in the US. The assumptions for the phenomena in this study were
      based upon Tu's cultural China and Confucian spirituality, as well as van Manen's
      phenomenological perspectives and Kleinman's ethnographic works. Fifteen Chinese
      immigrants with breast cancer in the US were recruited. The results reveal six
      cultural themes including family closeness, traditional Chinese values, religion,
      alternative therapy, art, prose and literature and Chinese support groups.

PMID- 11223057
TI  - Developing the nurse's role in patient education: rehabilitation as a case
      example.
AB  - Over the past decade considerable emphasis has been placed on the nurse's role in
      patient education. Despite this numerous studies have suggested that this aspect
      of nursing practice is under-developed. Using rehabilitation as a case example
      this paper explores the nursing contribution to patient education in five
      conditions: multiple sclerosis; arthritis; myocardial infarction; spinal injury
      and stroke. Although the literature identifies considerable potential for nurses
      to take a lead role in patient education this is rarely achieved in practice.
      Analyses of printed curricula from a range of courses indicate that nurses are
      not adequately prepared for patient education and that a reorientation of nurse
      education is required.

PMID- 11223059
TI  - Nursing research on physical activity: a feminist critique.
AB  - Studies on physical activity have rarely included women as research participants,
      and have been mainly conducted among Western populations. In this paper, nursing
      research on women's physical activity is analyzed and critiqued using a feminist
      perspective that respects and values women's own experiences and their
      diversities. An extensive literature search was conducted using computerized data
      retrieval systems and 47 empirical studies published in nursing literature were
      selected and analyzed. The critique is presented with three main themes emerged
      from the analysis: (a) "without considering women's own experiences"; (b)
      "implicit androcentric and ethnocentric assumptions"; (c) "without meaningful
      interactions". Based on the analysis, future directions for nursing research on
      physical activity are proposed.

PMID- 11223060
TI  - A critical review of the Delphi technique as a research methodology for nursing.
AB  - The Delphi technique is an approach used to gain consensus among a panel of
      experts. This is normally achieved through a series of rounds where information
      is fed back to panel members using questionnaires. It has been used extensively
      within social science research and is being increasingly employed by nurse
      researchers. This popularity has meant that the technique has been adapted in
      various ways and there is the possibility that the rigour associated with the
      original format has been threatened. This signals the need for a critical review
      of the Delphi as a robust and systematic approach to data collection. While there
      is a great volume of literature surrounding the "Delphi", there is a dearth of
      papers critically analysing the technique. This paper aims to examine critically
      the Delphi technique from a range of perspectives. Discussion will focus on
      problems of definition and the advantages and disadvantages and the techniques'
      application in nursing. The critique will be structured through an analysis of
      the key aspects of the Delphi process. These key aspects include analysis of
      sampling, anonymity, use of experts, rounds and application. The critical
      analysis highlights the increasing popularity of the Delphi and the modifications
      to the process which may cause methodological problems. Ultimately, the Delphi
      has much to offer in terms of gaining consensus from a wide range of individuals
      on specific topics.

PMID- 11223061
TI  - The burnout in nursing academicians in Turkey.
AB  - The purpose of this study was to determine the level of burnout in nursing
      academicians in Turkey and to investigate the variables which are strongly
      correlated with the burnout nursing education settings in Turkey. The sample of
      the study consisted of the nursing academicians working in the schools of nursing
      at the different universities in Turkey. Although the total number of nursing
      academicians in Turkey was 179, the subjects who agreed to participate in the
      research was 135. The Maslach Burnout Inventory (MBI) was used to measure
      burnout, after having been statistically tested for its validity and reliability
      in nursing education settings in Turkey. The multiple regression analysis was
      carried out in order to determine the main variables correlated with burnout,
      namely "the predictors" of each of the three components (emotional exhaustion
      (EE), depersonalization (DP), personal accomplishment (PA)) of burnout. The
      results indicated that the most significant predictor of EE was work-setting
      satisfaction, of DP was job pressure, and of PA was job satisfaction in nursing
      education settings in Turkey. Finally, these findings were compared with of those
      previous studies in the field.

PMID- 11223062
TI  - Telephone support group intervention for persons with hemophilia and HIV/AIDS and
      family caregivers.
AB  - The purpose of this pilot project was to test the feasibility of a telephone
      support group intervention for persons with hemophilia and HIV/AIDS and for their
      family caregivers. Their support needs were unique because they did not identify
      with predominant groups of persons with AIDS and were geographically dispersed
      from peers. The 12 week intervention involved separate telephone support groups
      for hemophiliacs and for family caregivers. The two groups, comprised of a
      predetermined maximum of six people, were co-led by a professional and a peer.
      The support group for family caregivers involved six people and the group for men
      with hemophilia included five people, including one peer facilitator and one
      professional facilitator in each group. The telephone support group discussions
      were taped, transcribed, and analyzed for prevalent themes. The peer and
      professional facilitators maintained weekly field notes. All participants
      reported that the telephone groups had a positive impact on meeting their support
      needs. They believed that they had benefitted from sharing information and that
      the support groups had decreased their feelings of isolation and loneliness.
      Participants, however, contended that the intervention should be longer than 12
      weeks.

PMID- 11223063
TI  - Woman-centred care.
AB  - Changes over the past decade have emphasised the individual service user and
      their relationship with the health service. Within the maternity services this
      has been interpreted as woman-centred care a result of key initiatives; the
      Winterton Report (House of Commons, 1992. Maternity Services. Second Report of
      the Health Committee (Winterton Report), Vol. 1. HMSO, London) and Changing
      Childbirth (DoH, 1993a, Changing childbirth: reports of the expert maternity
      group parts 1 & 2. HMSO, London). Changing Childbirth outlined key principles of
      the maternity services and the need for the woman (and her partner, if she
      wishes) to be the focus of care. The key principles are choice, continuity and
      control. High quality care depends on the recognition of individuals as having
      unique needs which continues to be reflected within contemporary policy documents
      (DoH, 1997, The new NHS: modern and dependable. HMSO, London). This paper
      presents findings related to the provision of woman-centred care from a national
      research and development study. The study design incorporated (i): a national
      survey which was undertaken with midwives, midwife supervisors and doctors; and
      (ii): in-depth case studies in which information was obtained through interviews
      with midwives, midwife supervisors, educators, managers, doctors and mothers.
      Midwives, at all levels, are involved in changing maternity service provision and
      adapting to new systems of care which aim to increase continuity of care and
      carer for the woman. The researchers sought to understand how woman-centred care
      was interpreted and experienced in practice. The findings have been used to
      identify the continuing educational needs of midwives, and to develop an open
      learning educational package to meet identified need. The curriculum was designed
      to enhance the move towards the provision of a more integrated woman-centred
      service.

PMID- 11223064
TI  - Introduction: bispecific antibodies.

PMID- 11223065
TI  - Bispecific human IgG by design.
AB  - A major obstacle facing the development of bispecific antibodies as therapeutics
      has been the formidable task of producing these complex molecules in sufficient
      quantity and purity for clinical trials. These production difficulties have been
      largely overcome with the advent of efficient methods for the secretion of
      designer bispecific antibody fragments such as diabodies and miniantibodies from
      Escherichia coli. In contrast, the creation of bispecific IgG by the coexpression
      of two different IgG is highly inefficient due to unwanted pairings of the
      component heavy and light chains. A robust technology for the creation of
      bispecific IgG has recently been developed that virtually precludes IgG
      contaminants, as reviewed here. This technology is anticipated to spur the
      clinical development of bispecific IgG and other bifunctional Fc-containing
      molecules such as antibody/immunoadhesin hybrids and bispecific immunoadhesins.

PMID- 11223066
TI  - Selection of cell binding and internalizing epidermal growth factor receptor
      antibodies from a phage display library.
AB  - The first step in developing a targeted cancer therapeutic is generating a ligand
      that binds to a receptor which is either tumor specific or sufficiently
      overexpressed in tumors to provide targeting specificity. For this work, we
      generated human monoclonal antibodies to the EGF receptor (EGFR), an antigen
      overexpressed on many solid tumors. Single chain Fv (scFv) antibody fragments
      were directly selected by panning a phage display library on tumor cells (A431)
      overexpressing EGFR or Chinese hamster ovary cells (CHO/EGFR cells) transfected
      with the EGFR gene and recovering endocytosed phage from within the cell. Three
      unique scFvs were isolated, two from selections on A431 cells and two from
      selections on CHO/EGFR cells. All three scFv bound native receptor as expressed
      on a panel of tumor cells and did not bind EGFR negative cells. Phage antibodies
      and multivalent immunoliposomes constructed from scFv were endocytosed by EGFR
      expressing cells as shown by confocal microscopy. Native scFv primarily stained
      the cell surface, with less staining intracellularly. The results demonstrate how
      phage antibodies binding native cell surface receptors can be directly selected
      on overexpressing cell lines or transfected cells. Use of a transfected cell line
      allows selection of antibodies to native receptors without the need for protein
      expression and purification, significantly speeding the generation of targeting
      antibodies to genomic sequences. Depending upon the format used, the antibodies
      can be used to deliver molecules to the cell surface or intracellularly.

PMID- 11223067
TI  - Ribosome display and affinity maturation: from antibodies to single V-domains and
      steps towards cancer therapeutics.
AB  - Protein affinity maturation using molecular evolution techniques to produce high
      affinity binding proteins is an important step in the generation of reagents for
      cancer diagnosis and treatment. Currently, the most commonly used molecular
      evolution processes involve mutation of a single gene into complex gene
      repertoires followed by selection from a display library. Fd-bacteriophage are
      the most popular display vectors, but are limited in their capacity for library
      presentation, speed of processing and mutation frequency. Recently, the potential
      of ribosome display for directed molecular evolution was recognised and developed
      into a rapid and simple affinity selection strategy using ribosome complexes to
      display antibody fragments (scFv). Ribosome display and selection has the
      potential to generate and display large libraries more representative of the
      theoretical optima for naive repertoires (10(14)). Even more important is the
      application of ribosome display for the affinity maturation of individual
      proteins by rapid mutation and selection cycles. These display strategies can
      apply to other members of the immunoglobulin superfamily; for example single V
      domains which have an important application in providing specific targeting to
      either novel or refractory cancer markers. We discuss the application of ribosome
      display and selection in conjunction with variable domain (CTLA-4) libraries as
      the first step towards this objective and review affinity maturation strategies
      for in vitro ribosome display systems.

PMID- 11223068
TI  - Design and application of diabodies, triabodies and tetrabodies for cancer
      targeting.
AB  - Multivalent recombinant antibody fragments provide high binding avidity and
      unique specificity to a wide range of target antigens and haptens. This review
      describes the design and expression of diabodies, triabodies and tetrabodies
      using examples of scFv molecules that target viruses (influenza neuraminidase)
      and cancer (Ep-CAM; epithelial cell adhesion molecule). We discuss the preferred
      choice of linker length between V-domains to direct the formation of either
      diabodies (60 kDa), triabodies (90 kDa) or tetrabodies (120 kDa), each with size,
      flexibility and valency suited to different applications for in vivo imaging and
      therapy. The increased binding valency of these scFv multimers results in high
      avidity (low off-rates). A particular advantage for tumour targeting is that
      molecules of 60-100 kDa have increased tumour penetration and fast clearance
      rates compared to the parent Ig (150 kDa). We highlight a number of cancer
      targeting scFv multimers that have recently successfully undergone pre-clinical
      trials for in vivo stability and efficacy. We also review the design of multi
      specific Fv modules suited to cross-link two or more different target antigens.
      These bi- and tri-specific multimers can be formed by association of different
      scFv molecules and, in the first examples, have been designed as cross-linking
      reagents for T-cell recruitment into tumours (immunotherapy), viral retargeting
      (gene therapy) and as red blood cell agglutination reagents (immunodiagnostics).

PMID- 11223069
TI  - Functional expression of chimeric receptor genes in human T cells.
AB  - Tumor immunotherapy has been limited to date by the poor antigenicity of most
      tumors, the immunocompromised state of many cancer patients, and the slow tumor
      penetration and short half-life of exogenously-introduced anti-tumor antibodies.
      Our group has developed a model immunotherapy system using a chimeric construct
      containing an antibody V region fused to a T cell activation molecule (T body)
      introduced by transfection into cytotoxic T cell lines, or populations of
      activated primary T or natural killer (NK) cells. In this study we have optimized
      the conditions needed for efficient transduction of human peripheral lymphocytes
      (PBL) using retroviral vectors pseudotyped with the gibbon ape leukemia virus
      (GaLV) envelope. Selection of packaging cells producing high virus titers was
      performed following transfection with constructs containing the green fluorescent
      protein (GFP), and FACS sorting. As a model chimeric receptor gene we used a
      tripartite construct consisting of a single-chain anti-TNP antibody variable
      region linked to part of the extracellular domain and the membrane spanning
      regions of the CD28 coreceptor molecule and joined at its 5' end to a gene
      fragment encoding the intracellular moiety of the gamma activation molecule
      common to the Fcepsilon and Fcgamma receptors. Enriched preparations of
      retrovectors containing this chimeric receptor and the GFP gene could stably and
      efficiently transduce human PBL co-activated by anti-CD3 and anti-CD28
      antibodies. In routine experiments, the transgene was expressed in 35-70% of the
      human T cells. Such lymphocytes express the chimeric receptors on their surface
      and upon stimulation with hapten immobilized on plastic they can produce IL-2.
      Transfectomas activated in this manner also undergo specific proliferation in the
      absence of exogenous IL-2. Moreover, the transduced lymphocytes could effectively
      lyse target cells expressing the TNP hapten on their surface. These studies
      establish the conditions for the optimal transfection of effector lymphocytes to
      redirect them against a variety of tumor targets.

PMID- 11223070
TI  - Development and applications of surface-linked single chain antibodies against T
      cell antigens.
AB  - In this report the use of surface-linkage to expand the potential experimental
      and therapeutic applications of single chain antibody (scFv) constructs is
      reviewed. A strategy for the generation and functional characterization of
      surface-linked scFvs that bind selectively to the T-cell proteins CD3epsilon,
      CD28, and CD152 (CTLA-4) is described in detail. Experimental examples are
      provided of the use of these constructs to study the positive and negative
      regulation of T-cell activation and to manipulate the in vivo immunogenicity of
      tumor cells. In addition, a novel system for Simultaneous T-cell Activation and
      Retroviral Transduction (START) is described in which retroviral packaging cells
      are rendered mitogenic for T lymphocytes by combined expression of surface-linked
      scFvs. Finally, the use of random mutagenesis and yeast surface display to
      increase the affinity and functional efficacy of scFv constructs is demonstrated.

PMID- 11223071
TI  - Antibody-cytokine fusion proteins for the therapy of cancer.
AB  - Advances in genetic engineering and expression systems have led to rapid progress
      in the development of antibodies fused to other proteins. These 'antibody fusion
      proteins' have novel properties and include antibodies with specificity for tumor
      associated antigens fused to cytokines such as interleukin-2 (IL2),
      granulocyte/macrophage colony-stimulating factor (GM-CSF), and interleukin-12
      (IL12). The goal of this approach to cancer therapy is to concentrate the
      cytokine in the tumor microenvironment and in so doing directly enhance the
      tumoricidal effect of the antibody and/or enhance the host immune response (T
      cell, B-cell or NK) against the tumor. In the past decade, multiple antibody
      cytokine fusion proteins have been developed with different specificities
      targeting a broad variety of tumors. These novel molecules retain both antibody
      and cytokine associated functions. In addition, in animals bearing tumors,
      antibody-cytokine fusion proteins are able to target the tumor and to elicit a
      significant anti-tumor response that in some cases results in a complete
      elimination of the tumor. These results suggest that antibody-cytokine fusion
      proteins have potential for use in the treatment of human cancer. In the present
      review, we describe strategies for construction of antibody-cytokine fusion
      proteins and discuss the properties of several antibody-cytokine fusion proteins
      with IgG genetically fused to the cytokines IL2, GM-CSF or IL12.

PMID- 11223072
TI  - Mechanisms of G-CSF- or GM-CSF-stimulated tumor cell killing by Fc receptor
      directed bispecific antibodies.
AB  - Studies with gene-modified mice have recently reinforced the importance of Fc
      receptor-mediated effector mechanisms for the therapeutic efficacy of rituxan and
      herceptin - two clinically approved antibodies for the treatment of tumor
      patients. We investigated Fc receptor-dependent tumor cell killing by mononuclear
      and granulocytic effector cells - comparing human IgG1 antibodies against CD20 or
      HER-2/neu with their respective FcgammaRI (CD64)-, FcgammaRIII (CD16)-, or
      FcalphaRI (CD89)-directed bispecific derivatives. With blood from healthy donors
      as effector source, human IgG1 and FcgammaRIII (CD16)-directed bispecific
      antibodies proved most effective in recruiting mononuclear effector cells,
      whereas tumor cell killing by granulocytes was most potently triggered by
      FcalphaRI-directed bispecific constructs. Granulocyte-mediated tumor cell lysis
      was significantly enhanced when blood from G-CSF- or GM-CSF-treated patients was
      investigated. Interestingly, however, both myeloid growth factors improved
      effector cell recruitment by different mechanisms, which were furthermore
      dependent on the tumor target antigen, and on the selected cytotoxic Fc receptor.

PMID- 11223073
TI  - Bispecific antibody-mediated destruction of Hodgkin's lymphoma cells.
AB  - CD30 is a molecule that is overexpressed on the surface of Hodgkin's lymphoma
      cells. Therefore, CD30 represents a potential candidate for immunotherapy. In
      this study, we report the in vitro results of two bispecific molecules (BSMs)
      that target CD30 to trigger molecules expressed on myeloid effector cells. The
      first BSM is composed of the Fab' fragment of a CD30-specific antibody, Ki-4,
      chemically linked to the Fab' fragment of the humanized CD64 (FcgammaRI)-specific
      antibody, H22 (H22xKi-4). In the second BSM, the H22 Fab' is replaced with the
      Fab' fragment of the CD89 (FcalphaR)-specific, antibody, A77 (A77xKi-4). Both
      BSMs were able to bind specifically to lymphoma cell lines expressing CD30. In
      addition, the H22xKi-4 and A77xKi-4 BSMs were shown to bind cells expressing CD64
      and CD89, respectively. Both BSMs mediated potent, dose-dependent antibody
      dependent cell-mediated cytotoxicity (ADCC) of CD30-expressing tumor cell lines
      when human monocytes were used as effector cells. In addition, freshly prepared
      polymorphonuclear leukocytes (PMNs) and effector cells in whole blood were able
      to mediate the ADCC of targets in conjunction with the A77xKi-4 BSM in some, but
      not all, experiments. Furthermore, we examined the ability of monocyte-derived
      macrophages (MDMs) to phagocytose CD30-expressing tumor cell lines in conjunction
      with the BSM. MDM-mediated phagocytosis was significantly enhanced in the
      presence of both BSMs. These results demonstrate that targeting lymphoma cells
      via CD30 to the myeloid high affinity Fc receptor for IgG and to the Fc receptor
      for IgA results in potent in vitro anti-tumor activity.

PMID- 11223074
TI  - A bispecific dsDNAxmonoclonal antibody construct for clearance of anti-dsDNA IgG
      in systemic lupus erythematosus.
AB  - High avidity anti-dsDNA IgG antibodies are believed to play an important role in
      the pathogenesis of the autoimmune disease systemic lupus erythematosus (SLE) and
      therefore attempts have been made to reduce the concentration of these antibodies
      in the bloodstream of SLE patients. Previously we reported the development of an
      antigen based heteropolymer (AHP), a bispecific complex prepared by using the
      avidin-biotin system to crosslink dsDNA to a mAb specific for the human
      erythrocyte (E) complement receptor. Our studies indicated that this AHP could
      bind anti-dsDNA antibodies to E and facilitate clearance of these autoantibodies
      from the circulation of a monkey without E destruction. Here we report an
      improved covalent crosslinking procedure and purification scheme in which the AHP
      construct is isolated by precipitation in 50% saturated ammonium sulfate. We used
      a dsDNA binding dye, PicoGreen, to demonstrate specificity of binding of dsDNA to
      E via the AHP. The efficacy of the AHP in binding IgG anti-dsDNA antibodies to E
      was demonstrated in a sensitive and quantitative assay, based on the time
      resolved fluorescence properties of europium-labeled anti-human IgG mAbs used to
      probe the E. We also used this assay to screen SLE patient and normal plasmas for
      levels of anti-dsDNA IgG. The results of this assay correlate very well with the
      Farr assay, and therefore this approach may be useful in the development of
      informative and specific assays for a variety of autoantibodies. Treatment of SLE
      plasmas with E-AHP under conditions close to physiological led to substantial
      reductions (> or = 90%) in anti-dsDNA titers. It should be possible to test these
      new AHP for their ability to target and safely remove IgG anti-dsDNA antibodies
      from the circulation in animal models.

PMID- 11223075
TI  - CD40 ligation for immunotherapy of solid tumours.
AB  - Tumour vaccines provide an important focus of current cancer research and are
      often based on the premise that although T-cells do respond naturally to certain
      tumours, this is usually weak and therefore ineffective at controlling disease.
      An integral and necessary part of a T-cell immune response involves triggering of
      CD40 on antigen-presenting cells (APC) by its ligand, CD154, on responding T
      helper (Th) cells. Furthermore, cytotoxic responses to tumours may fail because
      the Th-cell response is inadequate and unable to provide CD40 stimulation of APC.
      Growing evidence shows that stimulating APC with soluble CD40L or an agonistic
      anti-CD40 mAb can, at least in part, replace the need for Th cells and generate
      APC that are capable of priming cytotoxic T lymphocytes (CTL). The aim of this
      study was to investigate whether a range of solid tumours (CD40(-)) could be
      treated with anti-CD40 mAb. It was found that this treatment was effective, and
      correlated with the intrinsic immunogenicity and aggressiveness of the tumours.
      The mAb could be delivered locally or at a distal site, but increased antigen
      load provided by irradiated tumour cells added little to the effectiveness of the
      treatment. T-cells were required since cytokine (interferon-gamma) and CTL
      activity were demonstrated following treatment and the therapeutic efficacy was
      lost in nude mice. In addition, depletion of CD8(+) cells abrogated protection
      whilst depletion of CD4(+) cells had no effect. This study demonstrates that
      solid CD40(-) tumours are sensitive to anti-CD40 mAb therapy and that the
      response bypasses the need for Th cells.

PMID- 11223076
TI  - Pharmacokinetic-pharmacodynamic relationships of the bispecific antibody MDX-H210
      when administered in combination with interferon gamma: a multiple-dose phase-I
      study in patients with advanced cancer which overexpresses HER-2/neu.
AB  - INTRODUCTION: MDX-H210 is a Fab'xFab' bispecific antibody (BsAb) constructed
      chemically by crosslinking Fab' mAb 520C9 (anti-HER-2/neu) and Fab' mAbH22 (anti
      CD64). STUDY DESIGN AND OBJECTIVES: This was a dose escalation study of
      intravenous MDX-H210 (1-70 mg/m(2)), preceded 24 h beforehand by subcutaneous
      IFNgamma (50 microg/m(2) to up-regulate FcgammaRI) administered three times a
      week for 3 weeks. We investigated the pharmacokinetic-pharmacodynamic
      relationships between MDX-H210 C(max) and AUC and (i) MDX-H210 binding to
      peripheral blood monocytes and neutrophils, (ii) the peak plasma G-CSF, IL-6, IL
      8 and TNFalpha concentrations, and (iii) the observed clinical toxicity. RESULTS:
      23 patients (19F:4M; median age 51.5; range 25-72 y) with advanced HER-2/neu
      positive cancers (19 breast, three prostate and one lung) were studied. Plasma
      MDX-H210 concentrations over time, circulating numbers of monocytes and
      neutrophils, percent saturation of monocyte and neutrophil FcgammaRI, and plasma
      concentrations over time of G-CSF, IL-6, IL-8 and TNFalpha were measured and
      clinical toxicity monitored. The E(max) pharmacodynamic model best fitted the
      relationship of MDX-H210 C(max) and the maximum percent saturation of both
      monocytes (E(max)=74.6; EC(50)=0.9 microg/ml) and neutrophils (E(max)=66.2;
      EC(50)=2.3 microg/ml) on the first day of treatment. On the last day of
      treatment, day 19, these parameters were E(max)=57.0% and EC(50)=0.46 microg/ml
      for monocytes and E(max)=61.9% and EC(50)=0.26 microg/ml for neutrophils. No
      positive relationship was defined between the log MDX-H210 C(max) and the log
      peak plasma IL-6, G-CSF, TNF or IL-8 concentrations on day 1. On day 19 these
      plasma cytokine concentrations were undetectable post MDX-H210 therapy. There was
      no consistent relationship between MDX-H210 C(max) and the observed clinical
      toxicities. CONCLUSIONS: These data suggest that MDX-H210 C(max) and AUC could be
      related by the E(max) model to maximum percent FcgammaRI saturation on
      circulating monocytes and neutrophils in the patients studied. After day 1, the
      post MDX-H210 therapy cytokine response attenuated over time, consistent with
      desensitization. We did not find a relationship between log MDX-H210 C(max) and
      peak plasma cytokine concentrations or clinical toxicities.

PMID- 11223077
TI  - Bispecific antibody-targeted phagocytosis of HER-2/neu expressing tumor cells by
      myeloid cells activated in vivo.
AB  - Studies from our laboratory and others have established that both mononuclear
      phagocytes and neutrophils mediate very efficient cytotoxicity when targeted
      through Fc receptors using a suitable monoclonal or bispecific antibody (BsAb).
      Cross-linking an Fc receptor for IgG (FcgammaR) triggers multiple anti-tumor
      activities including superoxide generation, cytokine and enzyme release,
      phagocytosis and antibody-dependent cellular cytotoxicity (ADCC). In this report,
      using unfractionated leukocytes and two color flow cytometric analysis, we
      describe the phagocytic capacity of peripheral blood polymorphonuclear cells
      (PMN) and monocytes isolated from patients enrolled in a phase I clinical trial
      of MDX-H210 given in combination with IFNgamma. MDX-H210 is a BsAb targeting the
      myeloid trigger molecule FcgammaRI and the HER-2/neu proto-oncogene product
      overexpressed on a variety of adenocarcinomas. In this trial, cohorts of patients
      received escalating doses of MDX-H210 3 times per week for 3 weeks. Interferon
      gamma (IFNgamma) was given 24 h prior to each BsAb infusion. Our results
      demonstrate that monocytes from these patients were inherently capable of
      phagocytosing the HER-2/neu positive SK-BR-3 cell line and that addition of MDX
      H210 into the assay significantly enhanced the number of targets phagocytosed.
      Two days after administration of an immunologically active dose of MDX-H210 (10
      mg/m2), monocytes from these patients were able to phagocytose greater amounts of
      target cell material, indicating that these cells remained armed with
      functionally sufficient BsAb for at least 48 h. PMN from these patients very
      efficiently mediated phagocytosis through FcgammaRI after being treated with
      IFNgamma, but not before. We conclude that phagocytosis is not only an efficient
      mechanism of myeloid cell-mediated cytotoxicity, but may also be a mechanism by
      which antigens from phagocytosed cells can enter a professional antigen
      presenting cell for processing and presentation.

PMID- 11223078
TI  - Exogenous antigen targeted to FcgammaRI on myeloid cells is presented in
      association with MHC class I.
AB  - Vaccine therapy is attractive for prostate cancer patients because the tumor is
      slow growing (allowing time to augment host responses) and occurs in an older
      population less likely to tolerate more toxic treatments. We have constructed an
      expression vector based on a monoclonal antibody (mAb) that targets the high
      affinity receptor for IgG (FcgammaRI, CD64) which is exclusively expressed on
      myeloid cells including dendritic cells (DC). The heavy chain of mAb H22 CH2 and
      CH3 domains were removed and replaced with the gene for prostate specific antigen
      (PSA). Using that vector, we have constructed and purified FPH22.PSA, a fusion
      protein that targets PSA to FcgammaRI on antigen presenting cells (APC). This
      fusion protein has an apparent molecular mass of 80-83 kDa, binds to FcgammaRI
      with high affinity and expresses PSA. We demonstrate that FPH22.PSA targeted PSA
      was internalized and processed by the human myeloid THP-1 cell line resulting in
      presentation of MHC class I-associated PSA peptides and lysis of THP-1 by PSA
      specific human CTL. Moreover, pretreatment of THP-1 cells with antibodies to
      block either FcgammaRI or MHC class I, blocked lysis indicating that targeting to
      FcgammaRI results in presentation of exogenous antigen on MHC class I molecules.
      These data demonstrate that FPH22.PSA was processed in such a manner by the
      myeloid cell line to allow for presentation of immunodominant peptides in MHC
      class I molecules and suggests that uptake of antigen via FcgammaRI results in
      cross-priming.

PMID- 11223079
TI  - First tryptophan-containing weak neurotoxin from cobra venom.
AB  - With the purpose of studying structure-function relationships among weak
      neurotoxins (called so because of their low toxicity), we have isolated a toxin
      (WTX) from the venom of cobra Naja kaouthia using a combination of gel-filtration
      and ion-exchange chromatography. The amino acid sequence of the isolated toxin
      was determined by means of Edman degradation and MALDI mass spectrometry, the
      primary structure obtained being confirmed by 1H-NMR in the course of spatial
      structure analysis. The WTX sequence differs slightly from that of the toxin CM
      9a isolated earlier from the same venom (Joubert and Taljaard, Hoppe-Seyler's Z.
      Physiol. Chem., 361 (1980) 425). The differences include an extra residue (Trp36)
      between Ser35 and Arg37 as well as interchanging of two residues (Tyr52 and
      Lys50) in the C-terminal part of the toxin molecule. These changes improve the
      alignment that can be made with other weak neurotoxin sequences. An extended
      sequence comparison reveals that WTX is the first case of a tryptophan-containing
      weak neurotoxin isolated from cobra venom. WTX was found to compete with
      radioiodinated alpha-bungarotoxin for binding to the membrane-bound nicotinic
      acetylcholine receptor from Torpedo californica.

PMID- 11223080
TI  - A functional assay for paralytic shellfish toxins that uses recombinant sodium
      channels.
AB  - Saxitoxin (STX) and its derivatives are highly toxic natural compounds produced
      by dinoflagellates commonly present in marine phytoplankton. During algal blooms
      ("red tides"), shellfish accumulate saxitoxins leading to paralytic shellfish
      poisoning (PSP) in human consumers. PSP is a consequence of the high-affinity
      block of voltage-dependent Na channels in neuronal and muscle cells. PSP poses a
      significant public health threat and an enormous economic challenge to the
      shellfish industry worldwide. The standard screening method for marine toxins is
      the mouse mortality bioassay that is ethically problematic, costly and time
      consuming. We report here an alternative, functional assay based on electrical
      recordings in cultured cells stably expressing a PSP target molecule, the STX
      sensitive skeletal muscle Na channel. STX-equivalent concentration in the
      extracts was calibrated by comparison with purified STX, yielding a highly
      significant correlation (R=0.95; N=30) between electrophysiological
      determinations and the values obtained by conventional methods. This simple,
      economical, and reproducible assay obviates the need to sacrifice millions of
      animals in mandatory paralytic shellfish toxin screening programs.

PMID- 11223081
TI  - Occurrence of tetrodotoxin in the skin of a rhacophoridid frog Polypedates sp.
      from Bangladesh.
AB  - Twenty-three specimens of a tree-frog Polypedates sp. were collected from two
      locations (Mymensingh and Barisal) of Bangladesh in 1999, and assayed for their
      toxicity scores and toxin principle. Among the tissues, only the skin of the
      Mymensingh specimens was found to be toxic in mouse test, with the toxicity
      scores of 31-923MU/g. The toxin isolated from the skin was analyzed by high
      performance liquid chromatography, electrospray ionization-time of flight mass
      spectrometry and proton nuclear magnetic resonance, and characterized as
      tetrodotoxin, a toxin principle.

PMID- 11223082
TI  - Hematological studies on DIC-like findings observed in patients with snakebite in
      south China.
AB  - To clarify the characteristics of the hematological disturbances evoked by
      snakebite, we measured the antithrombin III (AT-III) activity, alpha2-plasmin
      inhibitor (alpha2-PI) activity, fibrinogen concentration (Fg) and level of fibrin
      degradation products (FDP) in 21 patients envenomed by several snakes in south
      China between August 1998 and October 1999. The hematological changes observed
      were as follows: the mean activities of AT-III were decreased in patients bitten
      by Ophiophagus hannah (Oh.), Bungarus fasciatus (Bf.), Hydrophis cyanocinctus
      (Hc.), Rhabdophis subminiatus (Rs.), and Trimeresurus stejnegeri (Ts.), while
      those of alpha2-PI were decreased in all patients in the present study; Fg was
      not detectable in the case of Rs. bite, and the Fg concentration after Ts., Oh.,
      Hc. and Bf. bites also decreased markedly thereby increasing the mean levels of
      FDP in all patients. It thus appeared that DIC-like syndrome was caused in
      patients envenomed by snakebite. In the present study, we found that patients who
      were bitten by Rs., which is still being classified as a non-venomous snake,
      exhibited complete defibrinogenation and severe hemorrhage without any evidence
      of severe multiple organ damage. We also found that patients with Ts. bite showed
      marked hemostatic disturbance without severe multiple organ damage. It is
      considered that such a discrepancy between the hematological findings and
      clinical symptoms could be a characteristic phenomenon of the DIC-like syndrome
      induced by snakebite, especially by Rs. and Ts. bites.

PMID- 11223083
TI  - Cross reactivity of different specific Micrurus antivenom sera with homologous
      and heterologous snake venoms.
AB  - Coral snakes are the only Elapids in America. They are represented by three
      genera: Leptomicrurus, Micruroides and Micrurus, of which the latter are the most
      abundant and diversified group. Little is known about the biochemistry of
      Micrurus venoms due to low availability. Here, we present a study on the cross
      reactivity of different specific Micrurus antivenom with homologous and
      heterologous snake venoms in order to contribute to the generation of more
      efficient antiserum for therapeutic purposes. The three specific antisera tested,
      anti-Micrurus corallinus, anti-Micrurus frontalis, and anti-Micrurus spixii, as
      well as the bivalent anti-elapid venom sera, raised against a mixture (50% each)
      of Micrurus frontalis and Micrurus corallinus venoms, were assayed by Western
      Blot against Micrurus and non-Micrurus elapid venoms. An antisera raised against
      a recombinant alpha-neurotoxin-like protein from Micrurus corallinus venom, only
      reacted in Western blot with its homologous venom, indicating that this protein
      is specific for Micrurus corallinus coral snake.

PMID- 11223084
TI  - An analysis of geographic and intersexual chemical variation in venoms of the
      spider Tegenaria agrestis (Agelenidae).
AB  - The spider Tegenaria agrestis is native to Europe, where it is considered
      medically innocuous. This species recently colonized the US where it has been
      accused of bites that result in necrotic lesions and systemic effects in humans.
      One possible explanation of this pattern is the US spiders have unique venom
      characteristics. This study compares whole venoms from US and European
      populations to look for unique US characteristics, and to increase our
      understanding of venom variability within species. This study compared venoms
      from T. agrestis males and females from Marysville, Washington (US), Tungstead
      Quarry, England (UK) and Le Landeron, Switzerland, by means of liquid
      chromatography; and the US and UK populations by insect bioassays.
      Chromatographic profiles were different between sexes, but similar within sexes
      between US and UK populations. Venoms from the Swiss population differed subtly
      in composition from UK and US venoms. No peaks were unique to the US population.
      Intersexual differences were primarily in relative abundance of components.
      Insect assays revealed no differences between US and UK venom potency, but female
      venoms were more potent than male. These results are difficult to reconcile with
      claims of necrotic effects that are unique to venoms of US Tegenaria.

PMID- 11223085
TI  - The effect of repeated gavage doses of fumonisin B1 on the sphinganine and
      sphingosine levels in vervet monkeys.
AB  - Fumonisins occur widely around the world in maize products intended for human and
      animal consumption posing a health hazard. Direct measurement of fumonisins in
      physiological fluids as a biomarker of exposure is not practicable, however
      fumonisins disrupt sphingoid metabolism by inhibition of sphinganine N
      acyltransferase. In this study the disruption in sphinganine (Sa) and sphingosine
      (So) levels in plasma and urine was measured in vervet monkeys (Cercopithecus
      aethiops) dosed with repeated gavages of 1mg fumonisin B1 (FB1)/kg body weight
      three times/week continuously over a 51-day period. The plasma Sa/So ratio
      reached a maximum (mean of 4.3) after 30 days in the dosed monkeys with a three
      fold increase above the ratio of the control monkeys and then declined slowly to
      double the value in controls after 51 days. The lack of a clear elevation in
      urinary Sa/So ratios after 51 days of multiple exposure in the dosed monkeys
      indicates that the plasma ratio is more sensitive than urinary changes in
      monkeys. This is confirmed by the plasma levels of liver function enzymes of
      which aspartate transaminase, glutamyl-transferase and lactate dehydrogenase were
      increased in the dosed monkeys, while the plasma indicators of renal function
      were not increased above the levels in the control monkeys. Thus repeated low
      doses of FB1 can cause sustained disruption of sphingoid metabolism.

PMID- 11223086
TI  - Isolation and identification of the cyanotoxin cylindrospermopsin and deoxy
      cylindrospermopsin from a Thailand strain of Cylindrospermopsis raciborskii
      (Cyanobacteria).
AB  - A strain of Cylindrospermopsis (Cyanobacteria) isolated from a fishpond in
      Thailand was examined for its taxonomy based upon morphology and 16S rRNA gene
      sequence. It was also examined for production of the hepatotoxic cyanotoxin
      called cylindrospermopsin (CYN) and deoxycylindrospermopsin (deoxy-CYN). The
      strain (CY-Thai) was identified as C. raciborskii (Woloszynska) Seenaya and Subba
      Raju based upon morphological examination which was confirmed by 16S rRNA gene
      sequences and phylogenetic comparisons based upon its 16S rRNA gene. The alkaloid
      heptatotoxin CYN was confirmed using mouse bioassay, HPLC and HPLC-MS/MS while
      deoxy-CYN was confirmed using HPLC-MS/MS. The mouse bioassay gave a minimum
      lethal dose at 250mg dry weight cells/kg body weight within 24h and 125mg/kg at
      72h, with signs of poisoning the same as in literature reports for CYN. HPLC
      chromatographic comparison of the CY-Thai toxin with standard CYN gave the same
      retention time and an absorbance maximum at 262nm. HPLC-MS/MS confirmed the
      presence of CYN (M+H 416) and deoxy-CYN (M+H 400). The CYN content in strain CY
      Thai was estimated at 1.02mg/g and approximately 1/10 of this amount for deoxy
      CYN. This is the first report from Asia of a CYN, deoxy-CYN producing
      Cylindrospermopsis raciborskii.

PMID- 11223087
TI  - Partial purification and characterization of a hemolysin (CAH1) from Hawaiian box
      jellyfish (Carybdea alata) venom.
AB  - We have isolated and characterized a novel hemolytic protein from the venom of
      the Hawaiian box jellyfish (Carybdea alata). Hemolysis of sheep red blood cells
      was used to quantitate hemolytic potency of crude venom extracted from isolated
      nematocysts and venom after fractionation and purification procedures. Hemolytic
      activity of crude venom was reduced or lost after exposure to the proteolytic
      enzymes trypsin, collagenase and papain. The activity exhibited lectin-like
      properties in that hemolysis was inhibited by D-lactulose and certain other
      sugars. Activity was irreversibly lost after dialysis of crude venom against
      divalent-free, 20mM EDTA buffer; it was optimal in the presence of 10mM Ca2+ or
      Mg2+. Two chromatographic purification methods, size fractionation on Sephadex G
      200 and anion exchange with quaternary ammonium, provided fractions in which
      hemolytic activity corresponded to the presence of a protein band with an
      apparent molecular weight of 42kDa by SDS-PAGE. We have designated this protein
      as CAH1. The N-terminal sequence of CAH1 was determined to be: XAADAXSTDIDD/GIIG.

PMID- 11223089
TI  - In vivo neurotoxicity of Androctonus australis hector scorpion venom: evidence
      that the supra-thoracic nervous system is not implicated in the clinical
      manifestations.
AB  - The severity of scorpion stings is related to the highly active neurotoxins in
      the venom. In this study, rats whose supra-spinal central nervous system was
      deprived of its peripheral connections were experimentally poisoned by the venom
      of Androctonus australis hector scorpion. Clinical signs of severity were not
      modified when the rats had previously undergone high medullar section. These
      results suggest that the supra-thoracic nervous system is not implicated in the
      neurotoxicity manifestations of scorpion envenomation.

PMID- 11223088
TI  - Effects of a Lasiodora spider venom on Ca2+ and Na+ channels.
AB  - The venom of a Brazilian spider, Lasiodora sp (Mygalomorphae, Theraphosidae), was
      screened for activity against ion channels using Ca2+ imaging and whole-cell
      patch clamp in GH3 cells. When tetrodotoxin (TTX) was present to block Na+
      channels, the venom abolished the Ca2+ oscillations that are normally present in
      these cells and reduced the basal level of intracellular Ca2+. Under patch clamp,
      the venom reduced the L-type Ca2+ channel conductance and caused a positive shift
      in its voltage dependence of activation. In addition to these effects, when
      applied without TTX, the venom also caused a slow and noisy increase in
      intracellular Ca2+. The sensitivity of this second effect to TTX suggested an
      effect on Na+ channels, which was tested using patch clamp. Control Na+ currents
      inactivated completely as a single exponential. Treatment with the venom did not
      affect the amplitude of I(Na), but caused it to divide in two slower exponential
      components plus a sustained component, all of which were suppressed by TTX. The
      venom also caused a negative shift in the voltage dependence of activation and
      steady-state inactivation of I(Na). The observed effects of this venom on whole
      cell currents explain the changes it causes in intracellular Ca2+ in GH3 cells
      and demonstrate that the venom of this spider is a source of toxins active
      against ion channels.

PMID- 11223090
TI  - Purification, amino-acid sequence and partial characterization of two toxins with
      anti-insect activity from the venom of the South American scorpion Tityus
      bahiensis (Buthidae).
AB  - We report here the isolation by a two-step chromatographic procedure of two new
      toxins from the South American scorpion Tityus bahiensis. Their amino-acid
      sequences and some of their biological features were established. The two toxins
      have different biological properties. Toxin TbIT-I had almost no activity or
      pharmacological effects in vertebrate tissues whereas it was lethal to house
      flies (LD50 80.0 ng/house fly). In contrast, Tb2-II was active against both
      mammals (intracerebroventricular injection of 100 ng/mouse was lethal) and
      insects (LD50 40.0 ng/house fly). The amino-acid sequences of these toxins were
      established and found to be similar (60-95%) to previously described beta-toxins
      from the Tityus genus. Based on the available comparative information, this study
      attempts identify possible structure-function relationships that may be
      responsible for the differences in bioactivity displayed by these toxins.

PMID- 11223091
TI  - A cytotoxicity assay for the detection and differentiation of two families of
      shellfish toxins.
AB  - There is an urgent need for an alternative to the mouse bioassay for the
      detection of algal toxins in shellfish on both analytical and animal welfare
      grounds. Several alternative methodologies have been described, but have not
      gained widespread acceptance to date, because each assay measures only one or a
      small number of related phycotoxins out of the increasing range that needs to be
      detected. A simple cytotoxicity assay using either the HepG2 or ECV-304 cell
      lines is described with two end-point measurements, which can detect and
      distinguish between two unrelated classes of phycotoxins. Morphological
      examination following 3h exposure to the sample enables the detection of the
      diarrhetic shellfish poisons, including okadaic acid and related toxins.
      Viability testing using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl
      tetrazolium bromide), following 24h exposure of the same cells to the sample,
      reveals a second class of toxin, which is most probably the newly-described
      toxin, azaspiracid. This assay should play an important role in shellfish
      monitoring in the future.

PMID- 11223092
TI  - Accumulation and depuration of paralytic shellfish poisoning toxins by purple
      clam Hiatula rostrata Lighttoot.
AB  - Purple clams (Hiatula rostrata Lighttoot) accumulated paralytic shellfish
      poisoning (PSP) toxins produced by a toxic strain of the dinoflagellate
      Alexandrium minutum Halim for subsequent study of toxin distribution during
      depuration (detoxification by a nontoxic microalgal diet or starvation). The
      results confirm the data in the literature concerning the high toxicity of the
      digestive gland, and the depuration efficiency between feed with nontoxic
      microalgae and starvation is similar. The toxin profile of the purple clams was
      similar with that of Alexandrium minutum at the end of the exposure period; GTX4
      and GTX1 were dominant. However, at the end of the depuration period, GTX3 and
      GTX2 were dominant. The non-visceral tissues were toxic after feeding with toxic
      algae. The toxicity was low and the profile were also similar with that of the
      toxic algae. No PSP toxins other than GTX-1, 2, 3 and 4 were detected in the
      experimental period.

PMID- 11223093
TI  - Monthly variations in diarrhetic toxins and yessotoxin in shellfish from coast to
      the inner part of the Sognefjord, Norway.
AB  - Monthly concentrations of diarrhetic shellfish poisoning (DSP) toxins and
      yessotoxin (YTX) in mussels from the coast to the inner part of the Sognefjord
      were determined. Mussels from nine locations were sampled from March to November
      1997. The DSP toxins and YTX were analysed by a colorimetric protein phosphatase
      2A (PP2A) inhibition assay or fluorometric HPLC, respectively. The mouse bioassay
      for DSP toxins was performed including either chloroform or diethyl ether in the
      final step of extraction. Using ether in the final step normally facilitated
      extraction of the DSP toxins, okadaic acid (OA) and dinophysis toxin-1 (DTX-1),
      while chloroform extraction included a wider spectrum of toxins, including YTX
      and a fast acting toxin(s) with neurotoxic effects. The concentrations of DSP
      toxins and YTX in mussels increased with distance from the coast. The highest
      concentrations of YTX (574 microg YTX/100 g mussel meat) and diarrhetic toxins
      (349 microg OA equivalents/100 g mussel meat) were measured in May and August,
      respectively, at locations in the inner part of the fjord. Since concentrations
      of DSP toxins and YTX in mussels increased with distance from the coast, the
      locations for mussel farming in the Sognefjord close to the coast, seem to be
      preferable.

PMID- 11223094
TI  - A cyclic peptide with high affinity to alpha-bungarotoxin protects mice from the
      lethal effect of the toxin.
AB  - Employing a combinatorial phage-peptide library, we previously identified the
      peptide MRYYESSLKSYPD (designated, library-peptide) that binds the snake toxin
      alpha-bungarotoxin (alpha-BTX) with a moderate binding constant of 10(-6)M
      (Balass et al., 1997. Proc. Natl. Acad. Sci. USA 94, 6054-6058). Under the
      experimental conditions employed, we found that the library-peptide did not
      protect mice from alpha-BTX lethality when injected concomitantly with the toxin.
      In order to improve the affinity of the peptide to alpha-BTX, we designed and
      synthesized the peptide CRYYESSLKSYCD (Met1 and Pro12 were replaced by
      cysteines), which following oxidation creates a single disulfide bond and forms a
      cyclic structure. The design of the cyclic peptide was based on our previous NMR
      analysis of the library-peptide/alpha-BTX complex (Scherf et al., 1997. Proc.
      Natl. Acad. Sci. USA 94, 6059-6064). The cyclic peptide binds alpha-BTX with
      affinity two orders of magnitude higher than that of the linear library selected
      peptide. Whereas the library peptide was ineffective, the cyclic peptide
      conferred protection from alpha-BTX lethality in mice, even when given 1h after
      the toxin injection. The cyclic peptide conferred complete protection from alpha
      BTX lethality in mice when administered 40min prior to toxin injection. However,
      experiments with the whole venom of the snake Bungarus multicinctus showed that
      protection could be achieved only when the cyclic peptide was administered
      concomitantly with the venom.

PMID- 11223095
TI  - Main features of Cortinarius spp. poisoning: a literature review.
AB  - INTRODUCTION: Cortinarius spp. poisoning is characterized by a delayed acute
      renal failure. The main features of this severe poisoning are still poorly known
      and often overlooked. The aim of this literature review is a better description
      of Cortinarius spp. poisoning. MATERIALS AND METHODS: The main medical databases
      were searched: Abstracts of Mycology, Current Contents, Medline, Pascal,
      Micromedex Poisindex, Toxicology abstracts, Toxline. All case reports that
      included a description of the clinical features of Cortinarius spp. poisoning
      were studied. RESULTS: 245 cases were collected and 90 cases could be analyzed in
      details. Gastrointestinal disorders are the main symptoms of the prerenal phase
      of the poisoning. They appear a few days after the ingestion of the mushrooms
      (median 3 days). The renal phase is delayed (median 8.5 days). Moderate and
      transient hepatic abnormalities have been reported. A severe hepatic failure can
      be ruled out. Muscular lesions are highly questionable. Treatment is supportive.
      No specific treatment can be recommended. Acute renal failure progressed towards
      chronic renal failure in half of the cases; intermittent hemodialysis or kidney
      transplantations were necessary in 70% of those cases. CONCLUSION: Cortinarius
      spp. poisoning is severe. Ingestion of Cortinarius species must be systematically
      suspected whenever tubulo-interstitial nephritis is diagnosed, especially as
      mushrooms may have been ingested 1-2 weeks before.

PMID- 11223096
TI  - Purification and properties of a proteinaceous toxin from the brackishwater clam
      (Corbicula japonica).
AB  - Water extracts from the brackishwater clam (Corbicula japonica) are lethal to
      mice upon i.v. injection. Further mouse assays confirmed that the toxicity
      exhibits a regional variation but no seasonal or sexual variations. The C.
      japonica toxin was purified from foot muscle, the most toxic tissue, successively
      by hydrophobic chromatography on Phenyl Sepharose, gel filtration on Sephacryl S
      200, hydrophobic FPLC on Phenyl Superose and cation-exchange FPLC on Mono S. The
      purified toxin had an i.v. LD50 of 11 microg/kg against mice. It was a weakly
      basic protein (pI 7.7) with a mol. wt of 23,000 and was rich in Gly, Glx and Asx
      but devoid of Met. Analysis of the purified toxin by a protein sequencer afforded
      no N-terminal amino acid. In addition to C. japonica, two species of freshwater
      clams belonging to the genus Corbicula, C. leana and C. sandai, were newly found
      to be toxic, although much less potent than C. japonica. Despite the difference
      in anatomical distribution of toxins among the three species of Corbicula clams,
      both C. leana and C. sandai toxins were closely similar in stability and mol. wt
      to the C. japonica toxin.

PMID- 11223097
TI  - Characterization, amino acid sequence and evolution of edema-inducing, basic
      phospholipase A2 from Trimeresurus flavoviridis venom.
AB  - Two phospholipases A2 (PLA2s) were purified from the venom of Trimeresurus
      flavoviridis (Crotalinae) inhabiting Tokunoshima island, Japan, and named PLA-A
      and PLA-B in the order of elution on a cation-exchange column. Lipolytic
      activities of PLA-A and PLA-B toward mixed micelles and liposomes were
      substantially lower than that of PLA2 (an [Asp49]PLA2) which had been isolated
      from the same venom. Both PLA-A and PLA-B consisted of 122 amino acids and
      contained aspartate at position 49 (the numbering according to the aligned
      sequences of PLA2s in Fig. 8), thus belonging to an [Asp49]PLA2 subgroup. PLA-A
      and PLA-B were identical in sequence with an exception at position 79. PLA-B
      contained Asn-Gly at positions 79 and 80 which are located in the beta-sheet
      region. On the other hand, PLA-A had beta-Asp-Gly and alpha-Asp-Gly in high and
      low proportion, respectively, at the corresponding positions which were produced
      from Asn-Gly through the base-catalyzed formation and hydrolysis of the
      succinimide type intermediate. Thus, PLA-A is derived from PLA-B. PLA-B is
      similar in sequence to PL-X, which had been purified from the venom of T.
      flavoviridis inhabiting Amami-Oshima island, Japan, and to PL-X', whose cDNA had
      been cloned from Tokunoshima T. flavoviridis venom gland, rather than PLA2. PLA-B
      showed strong edema-inducing activity, while PLA-A exhibited rather lower
      activity. The sequence around position 79 which constitutes a beta-turn segment
      seems to be crucial for edema-inducing activity. Phylogenetic tree of Tokunoshima
      T. flavoviridis venom PLA2 isozymes indicated that PLA-B and PL-X' diverged from
      PLA2 after branching of [Asp49]PLA2 forms and [Lys49]PLA2 forms.

PMID- 11223098
TI  - Microcystin contamination in fish from the Jacarepagua Lagoon (Rio de Janeiro,
      Brazil): ecological implication and human health risk.
AB  - Chronic and subchronic toxicity from exposure to microcystins, cyclic peptide
      liver toxins from certain cyanobacteria, poses an important hazard, which has
      received little study. No in vivo information exists on accumulation and transfer
      of microcystin from the food chain to humans. This paper present results of a 3
      year study that demonstrates bioaccumulation of microcystins by fish and
      potential rates of microcystin ingestion by humans. The study was carried out in
      a shallow coastal lagoon in the city of Rio de Janeiro (Jacarepagua Lagoon). Fish
      (Tilapia rendalli) were collected every 2 weeks from August 1996 to November
      1999. Microcystins were analyzed by HPLC in phytoplankton, fish liver and viscera
      while fish muscle tissue was analyzed by enzyme linked immunosorbant assay
      (ELISA). Phytoplankton samples, dominated by the genus Microcystis, were
      confirmed to contain microcystins as were fish livers, viscera and muscle tissue.
      During the entire study period, including times of low water bloom densities,
      fish muscle tissue contained concentrations of microcystins close to or above the
      recommended limit for human consumption (0.04 microg x kg(-1) day). Our findings
      demonstrate that microcystins can accumulate in fish tissue used for human
      consumption. Rates of ingestion routinely exceed the TDI guidelines as set by the
      WHO for drinking water. Appropriate epidemiology and risk assessment should be
      undertaken so that an acceptable TDI and appropriate risk management decisions
      can be made for human consumption of fish which are harvested from cyanobacterial
      blooms that contain cyanotoxins.

PMID- 11223099
TI  - Development of a polymerase chain reaction to distinguish monocellate cobra (Naja
      khouthia) bites from other common Thai snake species, using both venom extracts
      and bite-site swabs.
AB  - A PCR technique was used in this study to identify and distinguish monocellate
      cobra snake bites using snake venoms and swab specimens from snake bite-sites in
      mice from bites by other common Thai snakes. The sequences of nucleotide primers
      were selected for the cobrotoxin-encoding gene from the Chinese cobra (Naja atra)
      since the sequences of monocellate cobra (Naja kaouthia) venom are still unknown.
      However, the 113-bp fragment of cDNA of the cobrotoxin-encoding gene was detected
      in the monocellate cobra venom using RT-PCR. This gene was not found in the
      venoms of Ophiophagus hannah (king cobra), Bungarus fasciatus (banded krait),
      Daboia russelii siamensis (Siamese Russell's Viper, and Calloselasma rhodostoma
      (Malayan pit viper). Moreover, direct PCR could detect a 665-bp fragment of the
      cobrotoxin-encoding gene in the monocellate cobra venom but not the other snake
      venoms. Likewise, this gene was only observed in swab specimens from cobra snake
      bite-sites in mice. This is the first report demonstrating the ability of PCR to
      detect the cobrotoxin-encoding gene from snake venoms and swab specimens. Further
      studies are required for identification of this and other snakes from the bite
      sites on human skin.

PMID- 11223101
TI  - The Journal Welcomes its new partnerships with the International Society for
      Affective Disorders (ISAD) and the WPA Section of Affective Disorders.

PMID- 11223102
TI  - The evolution of life events research in psychiatry.

PMID- 11223103
TI  - Mitochondrial DNA polymorphisms in bipolar disorder.
AB  - BACKGROUND: Previous studies suggested mitochondrial abnormality in bipolar
      disorder: (1) possible contribution of parent-of-origin effect in transmission of
      bipolar disorder; (2) abnormal brain phosphorus metabolism detected by phosphorus
      31 magnetic resonance spectroscopy; (3) comorbidity of affective disorders in
      patients with mitochondrial encephalopathy; (4) increased levels of the 4977bp
      deletion of mitochondrial DNA (mtDNA) in the postmortem brains. We investigated
      mtDNA polymorphisms in association with bipolar disorder. METHODS: Twelve PCR
      fragments including all tRNA genes were examined by the single-strand
      conformation polymorphism method in 43 bipolar patients. All observed
      polymorphisms were sequenced. Association of these polymorphisms with bipolar
      disorder was examined by restriction fragment length polymorphism method in 135
      bipolar patients and 187 controls. RESULTS: In total, we found 28 polymorphisms
      including 14 polymorphisms that have not been reported previously. The A10398G
      polymorphism was significantly associated with bipolar disorder (10398A genotype:
      33.1% in bipolar, 22.2% in the control, P<0.05). Although this difference was not
      significant after Bonferroni correction, the CA haplotype of the 5178 and 10398
      polymorphisms was still significantly associated with bipolar disorder (CA
      haplotype: 33.6% in bipolar, 16.8% in control, P<0.001). Three rare mutations
      substituting evolutionary conserved bases; A5539G in tRNA(Trp) gene, A5747G in
      the origin of L-strand replication, and A8537G in ATPase subunit-6 and -8 genes,
      were found in patients with family history in which maternal transmission was
      suspected. DISCUSSION: The 5178C/10398A haplotype in mtDNA may be a risk factor
      of bipolar disorder (odds ratio, 2.4). Pathophysiological significance of rare
      mtDNA mutations needs to be verified in the future. This finding may imply the
      pathophysiological significance of mtDNA in bipolar disorder.

PMID- 11223104
TI  - Personality structure in patients with winter depression, assessed in a
      depression-free state according to the five-factor model of personality.
AB  - BACKGROUND: Depressive disorders are often associated with abnormalities of
      personality. This has also been found in Seasonal Affective Disorder, Winter
      Depression type (W-SAD), although relatively few and small studies have been done
      on this disorder so far, and mainly in the depressed phase. The aim of this study
      was to explore the personality structure and its possible background and clinical
      correlates in a larger group of patients with W-SAD, assessed in a non-depressed
      state, in the Five-Factor (or "Big Five") model of personality paradigm. METHODS:
      82 persons (87% of those asked) with diagnosed W-SAD, most of them originally
      self-referred, who had previously received light treatment at our unit, completed
      a Norwegian version of an inventory yielding the personality factors
      Agreeableness, Surgency, Conscientiousness, Emotional stability, and Openness to
      experience. RESULTS: Compared to a Norwegian reference group, the mean scores of
      the W-SAD patients were significantly lower on the factors agreeableness,
      surgency and emotional stability, and significantly higher on conscientiousness.
      However, very few patients had scores outside the reference range. The
      personality factors do not seem to be associated with the core physiological
      manifestations of winter depression, but rather with the psychic aspects, and are
      poor predictors of response to light treatment. LIMITATIONS: Some reservations
      should be made as to the generalisability of the findings to SAD patients in
      general. Thus, increased conscientiousness may reflect help-seeking behaviour.
      CONCLUSIONS: Personality structure does not seem to predict occurrence of
      physiological reactions to lack of adequate daylight in autumn/winter, and is a
      poor predictor of improvement after light treatment, but may predict the
      associated psychic symptomatology.

PMID- 11223105
TI  - Depressive conduct disorder: symptom patterns and correlates in referred children
      and adolescents.
AB  - BACKGROUND: In order to examine the validity of the ICD-10 diagnostic category of
      depressive conduct disorder (DCD), a sample of 58 patients (mean age 11.6) with
      this diagnosis consecutively referred to a teaching hospital was compared with
      151 patients with conduct disorder (CD) (mean age 12.3) and with 128 patients
      with depressive disorder (DD) (mean age 14.2). METHOD: Data on symptom profile,
      sociodemographic characteristics, duration of disorder, family history and
      psychosocial background were collected using the Maudsley item sheet. Comparison
      of the three groups was performed using SPSS. RESULTS: Controlling for age and
      gender differences, the DCD group had fewer biological depressive symptoms, fewer
      anxiety symptoms, less guilt and lower severity of overall depression compared to
      the DD group. They also displayed more self-injurious behaviour and had more
      adverse psychosocial circumstances than the DD subjects. Compared to the CD
      group, the DCD patients were less overtly aggressive and violent than the CD
      subjects, in addition to having significant depressive symptoms and a more
      frequent history of abuse. LIMITATIONS: The study was based on case-control and
      diagnosis had been reached after the discussion of clinicians involved in
      assessment. CONCLUSIONS: Overall, the results tentatively support the validity of
      this diagnostic subgrouping.

PMID- 11223106
TI  - Autonomic neurocardiac function in patients with major depression and effects of
      antidepressive treatment with nefazodone.
AB  - BACKGROUND: Major depression (MD) is associated with an augmented risk of
      cardiovascular mortality. One possible explanation for this association is that
      MD influences autonomic neurocardiac regulation (ANR). However, previous studies
      on this subject revealed conflicting results. METHODS: Using an autonomic test
      battery, which consisted of standardised measurements of heart rate variability
      (HRV) and blood pressure, we (1) compared ANR between 25 patients with DSM-III-R
      diagnosed MD and 60 healthy controls, and (2) investigated the autonomic effects
      of antidepressive treatment with nefazodone. RESULTS: Following multivariate
      analysis of all tests a significant reduction in HRV could only be shown for the
      Valsalva ratio amongst the depressives compared to controls. There was a
      significant inverse correlation between the HRV during deep respiration and both
      the severity of depression and the duration of the depressive episode. Serial HRV
      recordings revealed that both the mean resting heart rate and systolic blood
      pressure significantly decreased after 21 days of nefazodone treatment (average
      dosage 413 mg/day), whereas after 10 days (average dosage 270.8 mg/day) there
      were no striking changes compared to the pre-treatment values. During nefazodone
      treatment no significant changes in parasympathetic tone occurred. LIMITATIONS:
      ANR was not assessed in a randomised, placebo-controlled fashion. CONCLUSIONS:
      (1) Patients with MD may suffer from functional disturbances in the interaction
      between the sympathetic and parasympathetic autonomic tree. (2) The pattern of
      autonomic changes during treatment suggests that nefazodone induced a dose
      dependent, serotonergically-mediated down-regulation of the sympathetic tone.
      This mechanism might be responsible for nefazodone's properties of reducing
      anxiety.

PMID- 11223107
TI  - Comparison of consultation rates in primary care attenders with and without
      seasonal affective disorder.
AB  - BACKGROUND: There is a lack of published information about the consultation
      patterns of patients with seasonal affective disorder (SAD) in primary care, when
      compared with non-seasonal controls (NSCs). METHODS: Interview-confirmed SAD
      cases (n=90) were age- and sex-matched to two controls without significant
      seasonal morbidity on the Seasonal Pattern Assessment Questionnaire (SPAQ) (non
      seasonal controls, NSCs). A comparison of their consultation rates was made using
      data abstracted from primary care records over 4 years. RESULTS: The monthly rate
      of general practice consultations for SAD cases was significantly higher than
      that for NSCs. There was a significant difference in the median number of
      consultations in winter and autumn between the two groups. The matched
      multivariate analysis revealed that February and April were the independent
      months in which cases of SAD had significantly more consultations than NSCs.
      LIMITATIONS: Optimal diagnostic criteria for SAD have not been determined and our
      criteria may have been over-inclusive. CONCLUSION: In addition to a marked
      difference in monthly consultation rates between SAD cases and NSCs, the data
      demonstrate a difference in the pattern of seasonality of these rates. It is
      possible that increased frequency of consultation, in particular during the
      winter months (in patients who score as a case SPAQ), could be used as an
      indication of SAD in primary care.

PMID- 11223108
TI  - Sleep deprivation as a predictor of response to light therapy in major
      depression.
AB  - BACKGROUND: While the majority of depressed patients benefit from total sleep
      deprivation (TSD), light therapy is regarded as a first-line treatment only for
      seasonal affective disorder (SAD). The results of light therapy in nonseasonal
      major depressive disorder have been non-conclusive. We examined the correlation
      of TSD response and light therapy response in major depressed patients. METHODS:
      40 inpatients with major depressive disorder (seven with seasonal pattern, 33
      without seasonal pattern) were deprived of a night's sleep. The TSD responders,
      as well as the TSD nonresponders, were randomly assigned to receive adjunct light
      therapy either with bright white light (2500 lux) or dim red light (50 lux)
      during 2 weeks beginning on the third day after TSD. RESULTS: The 20 TSD
      responders improved significantly better under the light therapy than the 20 TSD
      nonresponders (according to the Hamilton Depression Rating Scale and the self
      rating depression scale Bf-S; v. Zerssen). LIMITATIONS: No significant difference
      could be found between the two light intensities. Since the patients were
      additionally treated with medication an interaction with the two adjunctive
      therapies cannot be excluded. CONCLUSION: Our results indicate that a positive
      TSD response in major depressed patients can be predicative of beneficial outcome
      of subsequent light therapy.

PMID- 11223109
TI  - Cholesterol and serotonin indices in depressed and suicidal patients.
AB  - BACKGROUND: Prolactin and cortisol responses to d-fenfluramine challenge of
      central serotonin are reduced in depressed and suicidal patients. Low serum
      cholesterol levels are also reported in suicidal behavior. Thus, we examined for
      a relationship between serum cholesterol and fenfluramine challenge responses in
      patients with depression and/or attempted suicide. METHODS: We studied 12
      patients and six controls. Blood was drawn for baseline serum cholesterol and the
      d-fenfluramine challenge test performed. RESULTS: Serum cholesterol levels were
      significantly lower in suicidal patients than in either non-suicidal patients or
      controls. However, neither the prolactin nor cortisol responses to d-fenfluramine
      correlated significantly with serum cholesterol levels. CONCLUSION: No
      relationship was found between serum cholesterol and these peripheral indices of
      serotonergic function.

PMID- 11223110
TI  - Morning sunlight reduces length of hospitalization in bipolar depression.
AB  - BACKGROUND: Bright artificial light improves non-seasonal depression. Preliminary
      observations suggest that sunlight could share this effect. METHODS: Length of
      hospitalization was recorded for a sample of 415 unipolar and 187 bipolar
      depressed inpatients, assigned to rooms with eastern (E) or western (W) windows.
      RESULTS: Bipolar inpatients in E rooms (exposed to direct sunlight in the
      morning) had a mean 3.67-day shorter hospital stay than patients in W rooms. No
      effect was found in unipolar inpatients. CONCLUSIONS: Natural sunlight can be an
      underestimated and uncontrolled light therapy for bipolar depression.
      LIMITATIONS: This is a naturalistic retrospective observation, which needs to be
      confirmed by prospective studies.

PMID- 11223111
TI  - Disinhibition of libido: an adverse effect of SSRI?
AB  - BACKGROUND: The article focuses on adverse drug reactions (ADR) to selective
      serotonin reuptake inhibitors (SSRI) concerning libido and sexual behaviour:
      cases of disinhibition of libido observed at the Psychiatric Hospital of
      Kilchberg near Zurich are described. METHOD: Within the scope of a drug safety
      program, the physicians of the hospital are regularly asked about severe and
      unexpected events under drug treatment. RESULTS: During remission of depression,
      five outpatients noticed an increase of libido experienced as strange to them,
      i.e. preoccupation with sexual thoughts, first appearance of promiscuity, of
      unsafe sexual intercourse, and of excessive pursuit of pornography, respectively,
      during administration, change in dose or discontinuation of SSRI. DISCUSSION: The
      case studies suggest that SSRI treatment might be associated with increase and
      disinhibition of libido. The phenomena are discussed as a "selective switch" into
      partly manic symptomatology or an induction of mixed states with prevailing
      sexual symptoms.

PMID- 11223112
TI  - Attentional processing and levels of symptomatology in Seasonal Affective
      Disorder (SAD): a preliminary longitudinal study.
AB  - DESIGN: The ability of performance on the emotional Stroop task to predict
      subsequent levels of symptomatology was examined within a longitudinal design in
      a group of individuals with SAD. Participants were tested in the winter when
      depressed and again in the summer when remitted. RESULTS: There was no change in
      emotional Stroop performance across the two time points. However, winter
      performance on the emotional Stroop task predicted symptom levels in the summer,
      even with winter symptom levels partialled out. The nature of this relationship
      was that a greater emotional Stroop effect for threat words in the winter was
      related to more improved mood in the summer. Furthermore, the strength of the
      relationship between lower winter emotional Stroop performance and more negative
      winter mood was associated with poorer mood in the summer.

PMID- 11223113
TI  - Depression in acutely medically ill elderly inpatients: a pilot study of early
      identification and intervention by formal psychogeriatric consultation.
AB  - BACKGROUND: Depressive disorders are common among acutely medically ill elderly
      inpatients, but they are poorly recognised and treated. A single blind,
      randomised and controlled pilot study evaluating the efficacy of early
      identification of depression and intervention by a psychogeriatric consultation
      was undertaken. METHOD: A two-stage screening procedure, using the Geriatric
      Depression Scale (GDS) and the Brief Assessment Schedule (BAS), was used to
      identify patients with depression. They were randomised into two groups: one
      received a psychogeriatric consultation and the other acted as a control group.
      Patients were followed-up at 10 weeks and 1 year interval. RESULTS: There were no
      differences between the intervention group and the control group on any outcome
      measure at 10 week and 1 year follow-up. There was poor concordance between
      recommended interventions and their implementation by the geriatricians in the
      intervention group. Also, there were no differences between the intervention and
      control groups in terms of the interventions received by the patient. The whole
      sample improved on almost all outcome measures from baseline to 10 weeks and 1
      year follow-up. CONCLUSIONS: Reasons for the absence of efficacy of
      psychogeriatric consultation and suggestions for improved methodology are
      discussed.

PMID- 11223114
TI  - Relationship between central serotonergic function and aggression in prepubertal
      boys: effect of age and attention-deficit/hyperactivity disorder.
AB  - Data indicate that diminished central serotonergic (5-HT) function is related to
      aggression in adults, but discrepant findings in children suggest that age or the
      presence of attention-deficit/hyperactivity disorder (ADHD) may influence this
      relationship. This study examined whether age or ADHD affects the association
      between 5-HT and aggression in 7-11-year old clinically-referred boys. Forty-six
      boys were divided into non-aggressive ADHD, aggressive ADHD, and aggressive non
      ADHD groups based on responses to interviews and ratings of behavior. Central 5
      HT function was assessed by measuring the prolactin response to a 1-mg/kg oral
      dose of D,L-fenfluramine. There was no significant difference in the prolactin
      response across the three groups of boys. Furthermore, when examined
      dimensionally, prolactin response was largely unrelated to ratings of aggression,
      even after controlling for ADHD. Finally, age was not associated with prolactin
      response, and had no effect on the relationship between prolactin response and
      aggression. This study provides further evidence that there is no clear
      relationship between central 5-HT function and aggression in disruptive boys.
      Moreover, these data do not confirm the hypothesis that age or the presence of
      ADHD influence the relationship between 5-HT and childhood aggression.

PMID- 11223115
TI  - Syndromes of schizophrenia and smooth-pursuit eye movement dysfunction.
AB  - There have been a number of studies on smooth pursuit eye movement (SPEM)
      dysfunction in schizophrenia. However, the association between SPEM dysfunction
      and particular clinical symptoms remains unclear. We examined SPEM dysfunction in
      relation to schizophrenic symptoms using both the positive/negative dichotomy and
      the three-syndrome model. Subjects included 78 patients with schizophrenia and 60
      healthy control subjects. SPEM performance was indexed by root mean square error.
      Symptom profiles were assessed using the Positive and Negative Syndrome Scale
      (PANSS), and the three-primary syndromes were identified by factor analysis of
      PANSS ratings (Psychomotor poverty: deficit negative symptoms; Disorganization:
      defined primarily by thought disorder; and Reality distortion: hallucinations and
      delusions). Compared with controls, the schizophrenia group showed significant
      impairment in global SPEM function. The three-syndrome approach produced more
      specific findings than the dichotomous model. Of the three syndromes, only the
      Disorganization dimension showed a significant association with increased global
      SPEM dysfunction. The specificity of SPEM dysfunction to Disorganization was
      verified in comparisons among schizophrenia subgroups and the control group. By
      contrast, the general domains of positive and negative symptoms were both found
      to be modestly associated with SPEM dysfunction. The separation of positive and
      negative symptoms that contribute to Disorganization from those that define
      Reality Distortion and Psychomotor Poverty has revealed significant new
      associations between SPEM and schizophrenic symptoms. These findings are
      interpreted in light of the proposal that the Disorganization syndrome is the
      central form of pathology in schizophrenia.

PMID- 11223116
TI  - An analysis of the specificity and the syndromal correlates of verbal memory
      impairments in schizophrenia.
AB  - It was investigated whether schizophrenic and depressive patients show a
      distinguishable mnestic profile. A further aim was to explore the
      psychopathological correlates of memory malperfomance in schizophrenic patients.
      For the present study, schizophrenic, depressive and healthy samples (n=25 each)
      were compared regarding their performance in the Rey Auditory Verbal Learning
      Test. Subjects' sociodemographic background variables were comparable except for
      age (entered as a covariate). Depressive and schizophrenic patients performed
      significantly worse than healthy controls regarding both short-term and long-term
      free recall as well as recognition. No differences occurred for two parameters
      reflecting proneness to interference. Negative schizophrenic symptomatology was
      strongly correlated with memory dysfunction before and after controlling for
      distractibility. The study supports previous research suggesting that memory
      impairments in schizophrenia are not an epiphenomenon of deficits in verbal
      fluency or an attentional impairment. The major deficit in both schizophrenic and
      depressive patients is inferred to be the capability to learn.

PMID- 11223117
TI  - No relationship between--141C Ins/Del polymorphism in the promoter region of
      dopamine D2 receptor and extrapyramidal adverse effects of selective dopamine D2
      antagonists in schizophrenic patients: a preliminary study.
AB  - Previous studies have shown that subjects without Del alleles of the--141C
      Ins/Del polymorphism in the promoter region of the dopamine D2 receptor (DRD2)
      gene have lower DRD2 density that those with one or two Del alleles. The present
      study aims to investigate the relationship between the -141C Ins/Del polymorphism
      and extrapyramidal adverse effects of bromperidol and nemonapride, antipsychotic
      drugs with a selective and potent DRD2 antagonistic property, in schizophrenic
      inpatients. Twenty-seven patients were treated with bromperidol at a fixed-dose
      of 6, 12 or 18 mg/day, and 25 patients were treated with nemonapride at a fixed
      dose of 18 mg/day. The duration of treatment with these drugs was 3 weeks. The
      Ins and Del alleles were determined by PCR. Extrapyramidal adverse effects were
      assessed by the Udvalg for Kliniske Undersogelser side effects rating scale. The
      subjects consisted of 38 homozygotes of the Ins allele and 14 heterozygotes of
      the Ins and Del alleles. There were no significant differences in the incidence
      or severity of extrapyramidal adverse effects between patients with and without
      the Del allele. It is possible that this result was due to a lack of statistical
      power. However, the present study suggests that the--141C Ins/Del polymorphism is
      not related to the development of extrapyramidal adverse effects during acute
      phase treatment with antidopaminergic agents.

PMID- 11223118
TI  - Roles of arginine vasopressin and atrial natriuretic peptide in polydipsia
      hyponatremia of schizophrenic patients.
AB  - Respective contributions of arginine vasopressin (AVP) and atrial natriuretic
      peptide (ANP) to the urinary sodium concentration were evaluated in 23
      naturalistic incidents of polydipsia-hyponatremia observed in 11 hospitalized
      schizophrenics (10 males and 1 female). The sodium concentration of the
      spontaneously excreted urine was examined before and after the forced water
      restriction. Before the water restriction, mean (+/-S.D.) plasma ANP was 52.8 +/-
      33.9 pg/ml (range = 6.9-137). Plasma AVP levels were below 0.3 pg/ml in 15
      episodes; relatively high levels (> or = 0.3) were noted in eight episodes. Means
      of urinary sodium concentration (mEq/l) were significantly higher in episodes
      with high AVP (> or = 0.3) alone (25.0 +/- 8.2, n=4), with high ANP (> 43) alone
      (21.3+/-7.4, n = 9), and with high AVP and ANP (26.8 +/- 6.4, n = 4) as compared
      to that of the low AVP (< 0.3) and ANP (< or = 43) group (13.5 +/- 3.7, n = 6).
      The data indicate that the elevated urinary sodium in polydipsic patients is
      possibly due to the AVP-induced antidiuresis and/or the ANP-induced natriuresis.
      In addition, we observed a close relationship between elevated plasma AVP and
      vomiting, suggesting that vomiting is one of the causal factors responsible for
      AVP elevations in this syndrome.

PMID- 11223119
TI  - Diagnosis of manic episodes in adolescent inpatients: structured diagnostic
      procedures compared to clinical chart diagnoses.
AB  - This study examined the accuracy of clinical chart diagnoses of manic episodes in
      adolescent psychiatric patients, as well as treatment selection and patient
      outcome. A consecutive sample of 120 consenting adolescent patients was assessed
      at admission, discharge, and 30 and 120 days post-discharge. Clinical chart
      diagnoses were compared to research-quality diagnoses involving structured
      interview, chart review, and consensus. Agreement statistics were computed, and
      the symptom and treatment differences were compared between patients for whom
      there was and was not diagnostic agreement. Clinical diagnoses of manic episodes
      were more common than research diagnoses, and the rate of agreement between
      diagnoses was low (kappa = 0.15). Patients diagnosed as experiencing a manic
      episode by the clinical chart, but not via the research procedure, had reduced
      severity scores on elation and activity, and higher scores on depression. These
      patients also had more severe scores on depressive symptoms at follow-up. Manic
      episodes were diagnosed more frequently by clinicians relative to research
      quality procedures. Patients who were diagnosed as experiencing manic episodes by
      the clinician, but not the research procedure, appeared to have depression and
      hostility, but not elation. The depression in these patients may not be
      adequately treated, and there are potential clinical implications of over
      diagnosis of manic episodes in adolescents.

PMID- 11223120
TI  - Factor analysis of the Communication Disturbances Index.
AB  - The present study utilized factor analysis to investigate possible underlying
      processes in schizophrenic thought disorder. Using the Communication Disturbances
      Index [CDI; Arch. Gen. Psychiatry, 53, (1996) 358], a measure of disruption in
      the communication of meaning from speaker to listener, we examined the speech of
      58 stable schizophrenia outpatients for six different types of referential
      communication disturbances. We calculated instances of disturbance per 100 words
      and then factor-analyzed our data using the SAS statistical package. Principal
      components analysis with an oblique rotation produced both a two- and a three
      factor solution, depending on factor inclusion criteria. In the three-factor
      solution, the first two factors reflected weaknesses in language structural
      organization and in concept-boundary definition, respectively. The third factor
      appeared to reflect weaknesses in specific facets of memory functioning. In the
      two-factor solution, the aforementioned structural organization and concept
      boundary definition factors were combined into a single executive functioning
      factor. Results from the study may be heuristic in the development of models of
      language disturbance in schizophrenia patients.

PMID- 11223121
TI  - Is somatization a habituation disorder? Physiological reactivity in somatization
      syndrome.
AB  - The present study investigates whether physiological activity may play a part in
      maintaining the amplified perception of bodily processes typical for
      somatization. Eighty-one persons were classified into three groups by means of a
      structured clinical interview: 24 patients with somatization syndrome, 34
      patients with somatization syndrome and comorbid major depression, and 23 healthy
      controls. Subjects completed four blocks of an attentional task, each of the
      blocks separated by resting periods. Physiological patterns demonstrated higher
      activity during mental tasks than during rest. The heart rate deceleration after
      changing from mental challenge to rest was less pronounced in the groups of
      patients with somatization syndrome than in controls. Moreover, patients with
      somatization syndrome reported feeling more and more tense during the
      investigation, while controls showed the tendency to habituate. The effects of
      heart rate and of feelings of tension partly replicated earlier findings, and
      demonstrated that physiological activity may interact with psychological
      processes in somatization.

PMID- 11223122
TI  - Auditory P300 event related potential and serotonin reuptake inhibitor treatment
      in obsessive-compulsive disorder patients.
AB  - Neuropsychological findings in obsessive-compulsive disorder (OCD) have been
      explained in terms of reduced cognitive shifting ability as a result of low
      levels of frontal inhibitory activity. This deficit could be reflected in an
      abnormal P300 component of the event-related potential. The improvement in
      cognitive processing due to pharmacological treatment would modify the P300
      component, bringing it close to that of normal controls. Nineteen patients
      suffering from OCD and 19 normal controls were recorded. We used a computerized
      version of the auditory 'odd-ball paradigm' to obtain the P300 component at the
      Pz electrode. Patients were tested twice, drug-free and under treatment with
      clomipramine in 250-300 mg doses. We observed the P300 component to have lower
      amplitude and longer latency in drug-free OCD patients when compared with
      controls. P300 amplitude in OCD increased after treatment, although this was
      supported only by a statistical trend. There was no modification in P300 latency
      after treatment. It is possible that inhibitory activity improves with treatment
      and allows patients to answer with more confidence, which results in an increase
      in P300 amplitude. This study suggests that cognitive dysfunction in OCD
      fluctuates with changes in the clinical associated with treatment, probably in
      relationship to central serotoninergic transmission.

PMID- 11223123
TI  - Characterisation of the growth and differentiation in vivo and in vitro-of
      bloodstream-form Trypanosoma brucei strain TREU 927.
AB  - Trypanosoma brucei TREU 927/4 has been chosen as the reference strain targeted
      for complete sequencing of the genome of the African trypanosome. This line is
      pleomorphic in mammalian hosts and is fly transmissible; however it is relatively
      unstable with respect to variable surface glycoprotein (VSG) expression.
      Therefore, we subjected TREU 927/4 to 27 rapid syringe passages through mice, and
      derived a cloned line which expressed Glasgow University Trypanozoon antigen type
      (GUTat) 10.1 with relative stability. This line also retained pleomorphism in the
      bloodstream, being able to generate homogeneous populations of stumpy forms in
      mice. Furthermore, these parasites remain able to transform to procyclic forms
      synchronously in vitro and can complete their life cycle in tsetse flies. The
      passaged cell line was also adapted to in vitro bloodstream-form culture and
      transfected with a construct encoding the tetracycline repressor (TETR) protein.
      The resulting TETR subline no longer expressed the GUTat 10.1 VSG but remained
      able to generate uniform populations of stumpy form cells in mice
      immunocompromised with cyclophosphamide. They could also differentiate to
      procyclic forms synchronously in vitro. The generated lines and analyses of their
      growth and differentiation will provide a basic resource for the analysis and
      interpretation of gene function in the T. brucei genome reference strain.

PMID- 11223124
TI  - Alternative splicing and sequence diversity of transcripts from the oncosphere
      stage of Taenia solium with homology to the 45W antigen of Taenia ovis.
AB  - Genes and transcripts which show homology to the host-protective 45W antigen of
      Taenia ovis have been cloned from the human parasite Taenia solium. The T. solium
      genes cloned in this study (TSO45) show conserved genomic structural features
      which are also features of the T. ovis 45W gene family. The TSO45 genes consist
      of a four exon and three intron structure. Eight TSO45 transcripts, encoded by at
      least five genes, were cloned from T. solium oncospheres and comparison of their
      DNA sequence indicates that some transcripts have arisen by alternative splicing,
      the first demonstration of exon inclusion/exon skipping in cestodes. Alternative
      splicing occurred with respect to both exons II and III with three splice
      variants identified from the TSO45-1 gene and two splice variants from TSO45-5.
      The proteins encoded by this family of genes contain putative N-linked
      glycosylation sites, an amino terminal secretory signal, a hydrophobic carboxy
      terminal sequence characteristic of GPI-anchored proteins and fibronectin type
      III motifs. These features are common to their T. ovis and Taenia saginata
      homologues. The similarities of the TSO45 genes cloned in this study with genes
      encoding host-protective antigens of T. ovis and T. saginata indicates that the
      encoded T. solium proteins are quite possibly antigenic and have potential use as
      a vaccine to prevent T. solium infection in the parasite's intermediate host. In
      this respect, the generation of sequence diversity and hence potential antigenic
      diversity through alternative splicing of TSO45 genes may have implications for
      the use of these proteins in vaccines against T. solium cysticercosis.

PMID- 11223125
TI  - Cloning of a pyruvate phosphate dikinase from Trypanosoma cruzi.
AB  - We have cloned and characterised a gene that encodes a putative pyruvate
      phosphate dikinase (PPDK) from Trypanosoma cruzi, an enzyme that catalyses the
      reversible conversion of phosphoenolpyruvate to pyruvate. PPDK is absent in
      mammalian cells, but has been found in a wide variety of other organisms,
      including plants and bacteria. In T. cruzi, two genes (PPDK1 and PPDK2) are
      present in a tandem array localised on a 1 Mbp chromosome. Northern and Western
      blot analyses indicates that PPDK is expressed as a 100-kDa protein in
      epimastigote, amastigote and trypomastigote forms. PPDK1 and PPDK2 encode an
      identical protein of 100.8 kDa with a C-terminal extension ending with the
      sequence AKL, a signal for glycosomal import. Both T. cruzi and T. brucei enzymes
      possess a 23-residue insertion, that is absent in other PPDKs. A three
      dimensional alignment with the crystal structure of the enzyme from Clostridium
      symbiosum predicts that this insertion is located on the surface of the
      nucleotide-binding domain. Phylogenetic studies indicate that bacterial and
      protist PPDKs cluster as a separate group from those of plants. The evolutionary
      implications and possible role of this enzyme in T. cruzi is discussed.

PMID- 11223126
TI  - Sequence diversity and antigenic polymorphism in the Plasmodium yoelii p235 high
      molecular mass rhoptry proteins and their genes.
AB  - A gene family in Plasmodium yoelii YM encodes p235, a group of high molecular
      mass erythrocyte-binding rhoptry proteins. Sequence analysis of 6 cDNA clones
      from the 3' end of expressed p235 genes divided them into two groups
      corresponding to genes on chromosomes 1, and 5 and 6, respectively. Twelve
      partial p235 protein sequences, derived from cDNA sequences from the region with
      greatest protein sequence similarity to Plasmodium vivax RBP2, fell into three
      groups, together with one chimeric sequence. A comparison of these cDNA sequences
      with genomic DNA sequences from the same region suggested that only a subset of
      the gene repertoire is expressed. Three genomic DNA clones, derived from the 5'
      end of p235 genes designated E1, E2, and E5 and located on chromosome 5/6, were
      also obtained and aligned with sequences from the known E8 and E3 genes. In the
      region of overlap there was only approximately 27% protein sequence identity,
      indicating that the sequences in this p235 N-terminal region are more diverse
      than at the C-terminal end. This sequence variation in the expressed genes did
      not result in antigenically different rhoptry proteins as detected with a panel
      of p235-specific mAbs. Only one schizont out of 500 examined with mAb 25.86
      appeared to be an antigenic variant, with all of the developing merozoites in
      this schizont being mAb 25.86 negative. No other antigenic variants were detected
      with the other antibodies, and therefore it is likely that these antibodies
      recognise conserved epitopes.

PMID- 11223127
TI  - A novel anti-inflammatory oligopeptide produced by Entamoeba histolytica.
AB  - The monocyte locomotion inhibitory factor (MLIF), a heat-stable oligopeptide
      found in the supernatant fluid of Entamoeba histolytica axenic cultures was
      isolated by ultra-filtration, gel-sieve chromatography and high powered liquid
      chromatography (HPLC), and its primary structure (Met-Gln-Cys-Asn-Ser)
      established by Edman sequencing and mass-spectrometry (MS). A synthetic peptide
      had the same selective anti-inflammatory features as the native material in
      comparable concentrations: in vitro inhibition of the locomotion in human
      peripheral blood monocytes, and of the respiratory burst in the same cells and in
      human neutrophil polymorphonuclear leucocytes; and in vivo depression of delayed
      hypersensitivity skin reactions to dinitrochlorobenzene in guinea pigs. This
      oligopeptide is apparently synthesized by the ameba as suggested by [(35)S]-Cys
      and Met incorporation, probably as part of a larger molecule, from which it is
      cleaved by proteolysis. The full sequence was not found in the 431 available E.
      histolytica protein sequences. The factor may contribute to the unexpected
      paucity of the late inflammatory reaction found in advanced invasive amebiasis
      and, perhaps in consequence, to the regeneration without scarring (restitutio ad
      integrum) of the affected organs that is observed following successful treatment
      of this disease

PMID- 11223128
TI  - Rapid recombination among transfected plasmids, chimeric episome formation and
      trans gene expression in Plasmodium falciparum.
AB  - Although recombination is known to be important to generating diversity in the
      human malaria parasite P. falciparum, the low efficiencies of transfection and
      the fact that integration of transfected DNA into chromosomes is observed only
      after long periods (typically 12 weeks or more) have made it difficult to
      genetically manipulate the blood stages of this major human pathogen. Here we
      show that co-transfection of a P. falciparum line with two plasmids, one
      expressing a green fluorescent protein (gfp) reporter and the other expressing a
      drug resistance marker (Tgdhfr-ts M23), allowed selection of a population in
      which about approximately 30% of the parasites produce GFP. In these GFP
      producing parasites, the transfected plasmids had recombined into chimeric
      episomes as large as 20 kb and could be maintained under drug pressure for at
      least 16 weeks. Our data suggest that chimera formation occurs early (detected by
      7--14 days) and that it involves homologous recombination favored by presence of
      the same P. falciparum 5'hrp3 UTR promoting transcription from each plasmid. This
      indicates the presence of high levels of homologous recombination activity in
      blood stage parasites that can be used to drive rapid recombination of newly
      introduced DNA, study mechanisms of recombination, and introduce genes for trans
      expression in P. falciparum.

PMID- 11223129
TI  - The malaria parasite Plasmodium falciparum possesses a functional thioredoxin
      system.
AB  - The thioredoxin system consists of the NADPH dependent disulphide oxidoreductase
      thioredoxin reductase (TrxR) which catalyses the reduction of the small protein
      thioredoxin. This system is involved in a variety of biological reactions
      including the reduction of deoxyribonucleotides, transcription factors and
      hydrogen peroxide. In recent years the TrxR of the malaria parasite Plasmodium
      falciparum was isolated and characterised using model substrates like 5,5'
      dithiobis (2-nitrobenzoic acid) (DTNB) and Escherichia coli thioredoxin. Here we
      report on the isolation of a cDNA encoding for P. falciparum thioredoxin (PfTrx)
      and the expression and characterisation of the recombinant protein, the natural
      substrate of PfTrxR. The deduced amino acid sequence of PfTrx encodes for a
      polypeptide of 11715 Da and possesses the typical thioredoxin active site motif
      CysGlyProCys. Both cysteine residues are essential for catalytic activity of the
      protein, as shown by mutational analyses. Steady state kinetic analyses with
      PfTrxR and PfTrx in several coupled assay systems resulted in K(m)-values for
      PfTrx in the range of 0.8--2.1 microM which is about 250-fold lower than for the
      model substrate E. coli thioredoxin. Since the turnover of both substrates is
      similar, the catalytic efficiency of PfTrxR to reduce the isolated PfTrx is at
      least 250-fold higher than to reduce E. coli thioredoxin. PfTrx contains a
      cysteine residue in position 43 in addition to the active-site cysteine residues,
      which is partially responsible for dimer formation of the protein as demonstrated
      by changing this amino acid into an alanine residue. Using DTNB we showed that
      all three cysteine residues present in PfTrx are accessible to modification by
      this compound. Surprisingly the first cysteine residue of the active site motif
      (Cys30) is less accessible than the second cysteine (Cys33), which is highly
      prone to the modification. These results suggest a difference in the structure
      and reaction mechanism of PfTrx compared to other known thioredoxins.

PMID- 11223130
TI  - Anopheles gambiae laminin interacts with the P25 surface protein of Plasmodium
      berghei ookinetes.
AB  - Laminin is a major constituent of the basal lamina surrounding the midgut of the
      malaria vectors that has been implicated in the development of the Plasmodium
      oocyst. In this report we describe the cloning of the Anopheles gambiae gene
      encoding the laminin gamma 1 polypeptide and follow its expression during
      mosquito development. To further investigate the putative role of laminin in the
      transmission of the malaria parasite we studied the potential binding of the P25
      surface protein of Plasmodium berghei using a yeast two-hybrid system.
      Heterodimer formation was observed and does not require any additional protein
      factors since purified fusion proteins can also bind each other in vitro. Laminin
      gamma 1 also interacts with the paralogue of P25, namely P28, albeit more weakly,
      possibly explaining why the two parasite proteins can substitute for each other
      in deletion mutants. This represents the first direct evidence for molecular
      interactions between a surface protein of the Plasmodium parasite with an
      Anopheles protein; the strong interplay between laminin gamma 1 and P25 suggests
      that this pair of proteins may function as a receptor/ligand complex regulating
      parasite development in the mosquito vector.

PMID- 11223131
TI  - A bifunctional dihydrofolate synthetase--folylpolyglutamate synthetase in
      Plasmodium falciparum identified by functional complementation in yeast and
      bacteria.
AB  - Folate metabolism in the human malaria parasite Plasmodium falciparum is an
      essential activity for cell growth and replication, and the target of an
      important class of therapeutic agents in widespread use. However, resistance to
      antifolate drugs is a major health problem in the developing world. To date, only
      two activities in this complex pathway have been targeted by antimalarials. To
      more fully understand the mechanisms of antifolate resistance and to identify
      promising targets for new chemotherapies, we have cloned genes encoding as yet
      uncharacterised enzymes in this pathway. By means of complementation experiments
      using 1-carbon metabolism mutants of both Escherichia coli and Saccharomyces
      cerevisiae, we demonstrate here that one of these parasite genes encodes both
      dihydrofolate synthetase (DHFS) and folylpolyglutamate synthetase (FPGS)
      activities, which catalyse the synthesis and polyglutamation of folate
      derivatives, respectively. The malaria parasite is the first known example of a
      eukaryote encoding both DHFS and FPGS activities in a single gene. DNA sequencing
      of this gene in antifolate-resistant strains of P. falciparum, as well as drug
      inhibition assays performed on yeast and bacteria expressing PfDHFS--FPGS,
      indicate that current antifolate regimes do not target this enzyme. As PfDHFS-
      FPGS harbours two activities critical to folate metabolism, one of which has no
      human counterpart, this gene product offers a novel chemotherapeutic target with
      the potential to deliver a powerful blockage to parasite growth.

PMID- 11223132
TI  - The Plasmodium falciparum knob-associated PfEMP3 antigen is also expressed at pre
      erythrocytic stages and induces antibodies which inhibit sporozoite invasion.
AB  - The expression of the pfemp3 gene and the corresponding PfEMP3 knob-associated
      protein in the pre-erythrocytic stages of Plasmodium falciparum was demonstrated
      by RT-PCR, Western blots, IFAT and IEM. The antigen was found on the surface of
      the sporozoite and in the cytoplasm of mature hepatic stage parasites.
      Immunological cross-reactivity was observed with sporozoites from the rodent
      malaria parasites Plasmodium yoelii yoelii and Plasmodium berghei and was
      exploited to assess a potential role of this protein at the pre-erythrocytic
      stages. Specific antibodies from immune individuals were found to inhibit P.
      yoelii yoelii and P. berghei sporozoite invasion of primary hepatocyte cultures.
      PfEMP3 should now be added to the small list of proteins expressed at the pre
      erythrocytic stages of P. falciparum, and its vaccine potential now deserves to
      be investigated.

PMID- 11223133
TI  - Molecular, cellular and functional characterizations of a novel ICAM-like
      molecule of the immunoglobulin superfamily from Leishmania mexicana amazonensis.
AB  - A molecule with two immunoglobulin (Ig) domains cloned from Leishmania mexicana
      amazonensis was characterized to have a sequence homology to the Ig domains of an
      ICAM-like molecule telencephalin, cloned from the brain of mammals, as well as to
      the variable domains of human immunoglobulin lambda light chain. The molecule
      therefore appears to be an ICAM-like molecule as well as a member of the
      immunoglobulin superfamily. We thus named it ICAM-L for Leishmania ICAM. The gene
      was coamplified with the ribonucleotide reductase M(2) subunit gene responsible
      for hydroxyurea resistance from hydroxyurea (Hu)-resistant Leishmania variants.
      As expected, an increase of the ICAM-L protein as well as an increase of the
      specific ICAM-L transcript of 2.1 kb was detected in the Hu-resistant variants
      with increasing doses of the drug used for resistance selection. Structurally,
      ICAM-L is more similar to the secretory adhesive molecules, such as 1Bgp and the
      link protein of the immunoglobulin superfamily, in that it lacks a transmembrane
      region and a GPI anchor sequence. Although ICAM-L was mainly localized in the
      nucleus of the parasite by confocal microscopy, however, detailed studies by
      electron microscopy and FACS analysis indicated that the protein was also
      localized on the surface of the parasite. The surface localization of the protein
      was furthered strengthened by the observations that anti-ICAM-L or ICAM-L itself
      can significantly block the binding of the parasite to macrophages. The blocking
      of the attachment of parasite to macrophages may indicate that ICAM-L functions
      as an intercellular adhesive molecule.

PMID- 11223134
TI  - The cell cycle of Entamoeba invadens during vegetative growth and
      differentiation.
AB  - The cell division cycle of Entamoeba invadens was studied during vegetative
      growth of trophozoites and during their differentiation into cysts. During
      vegetative growth of trophozoites, it was observed that DNA synthesis typically
      continued after one genome content had been duplicated. During encystation, DNA
      synthesis was arrested after 4n genome content had been synthesised. Using multi
      parameter flow cytometry, the light scattering properties of cysts and
      trophozoites were studied. The cytoplasmic granularity, reflected by the side
      scatter of light, was proportional to DNA content of trophozoites, whereas cysts
      with similar DNA contents showed heterogeneity in their cytoplasmic granularity.
      Dynamic changes in the intracellular calcium pools were observed during
      differentiation of trophozoites to cysts. Comparison of E. invadens and Entamoeba
      histolytica cell cycles suggest that both organisms may have similar regulatory
      processes during cell division and differentiation. Since E. histolytica cannot
      be induced to encyst in axenic culture, analysis of the E. invadens cell cycle
      during encystation may be useful for identifying homologous processes in
      E.histolytica.

PMID- 11223135
TI  - Use of the elongation factor-1 alpha gene in a polymerase chain reaction-based
      restriction-fragment-length polymorphism analysis of genetic heterogeneity among
      Blastocystis species.

PMID- 11223136
TI  - Bradyzoite-specific expression of a P-type ATPase in Toxoplasma gondii.

PMID- 11223137
TI  - Conserved regions of the Plasmodium yoelii rhoptry protein RhopH3 revealed by
      comparison with the P. falciparum homologue.

PMID- 11223139
TI  - Thiolated dermal bovine collagen as a novel support for bioactive substances-
      conjugation with lysozyme.
AB  - Thiol groups were introduced to dermal bovine collagen (DBC) by the reaction with
      gamma-thiobutyrolactone. Thiolated DBC reacted with 2-pyridyl disulfide group
      introduced to lysozyme to form DBC-lysozyme conjugate through disulfide bridge.
      The enzymatic activity of freshly prepared conjugate was almost unchanged during
      ten consecutive runs over one month. The DBC-lysozyme conjugate showed the
      maximum activity at pH 6.3, on the contrary, that of native lysozyme was pH 9.0.
      Thermal stability of lysozyme was enhanced by the conjugation with DBC. The
      present results showed that the conjugation using thiolated collagen could be one
      of the useful alternative approaches to modify collagen with bioactive molecules.

PMID- 11223138
TI  - Acyl-CoA binding protein is essential in bloodstream form Trypanosoma brucei.

PMID- 11223140
TI  - Characterization of the promoter and upstream activating sequence from the
      Pseudomonas alcaligenes lipase gene.
AB  - Pseudomonas alcaligenes secretes a lipase with a high pH optimum, which has
      interesting properties for application in detergents. The expression of the
      lipase is strongly dependent on the presence of lipids in the growth medium such
      as soybean oil. The promoter of the gene was characterized and found to have
      resemblance to sigma54 controlled promoters, which are known to be tightly
      regulated. The transcription start was mapped precisely downstream of a sequence
      with close similarity to the -12/-24 consensus sequence of sigma54 controlled
      promoters. Interestingly, a hyperproducer mutant strain was isolated and found to
      have a C to T mutation in the -12/-24 promoter consensus region. In addition an
      Upstream Activating Sequence (UAS) with homology to sigma54 UAS consensus
      sequences was identified. It was demonstrated that an increase of the distance
      from the UAS to the transcription start or the deletion of the UAS results in
      significantly lower expression levels of lipase. A systematic mutational analysis
      of the UAS sequence has resulted in a variant with an increased lipase
      expression.

PMID- 11223141
TI  - Development of an Escherichia coli whole cell biocatalyst for the production of L
      amino acids.
AB  - A whole cell biocatalyst for the enzymatic production of L-amino acids from
      hydantoins was created by coexpressing the genes encoding the L-hydantoinase, the
      L-N-carbamoylase and the hydantoin racemase from Arthrobacter aurescens in
      Escherichia coli. In order to construct a well balanced reaction system the
      enzymatic activity in the cells was varied by using vectors with different copy
      numbers for expression of the genes. Derivatives of pSC101, pACYC184 and pBR322
      were employed for the various constructions and in one construct the hydantoinase
      gene was integrated into the E. coli chromosome. All constructs carried the E.
      coli rhamnose promoter system enabling gene expression control by transcriptional
      regulation. The productivity for L-tryptophan from the corresponding hydantoin
      was more than 6-fold higher than achieved with Arthrobacter aurescens.

PMID- 11223142
TI  - Secretory pathway limits the enhanced expression of classical swine fever virus
      E2 glycoprotein in insect cells.
AB  - The 3' untranslated region (UTR) is an important element that determines the
      level of recombinant protein expression via baculovirus vectors. Previous work
      using chloramphenicol acetyl transferase as reporter has shown that p10-promoter
      based baculovirus vectors with the authentic p10 3' UTR resulted in higher
      expression levels than vectors carrying an SV40 early terminator, as part of a
      lacZ selection cassette. To examine whether a similar increase in expression
      levels could be obtained for baculovirus-expressed glycoproteins, the classical
      swine fever virus E2 antigen was used as a model. With the authentic p10 3' UTR
      higher levels of E2 transcript were found than in the presence of the SV40
      terminator. This higher number of transcripts was accompanied by elevated levels
      of intracellular, non-glycosylated E2 protein. However, the levels of
      intracellular glycosylated forms of E2 and of extracellular E2 were similar for
      both type of terminators. These results show that translation of the recombinant
      mRNA is not the rate limiting step in the expression of glycoproteins, but the
      downstream processing and secretion of the translation products.

PMID- 11223143
TI  - Dynamic responses of Pseudomonas fluorescens DF57 to nitrogen or carbon source
      addition.
AB  - Cultures of Pseudomonas fluorescens DF57 were grown on different carbon and
      nitrogen sources. Glucose, succinate and acetate were used as carbon source and
      pulsed to an aerobic steady-state cultivation of P. fluorescens DF57 at D = 0.1
      h(-1) with citrate as limiting carbon source. Glucose was utilised with the
      fastest uptake rate (19.4 C mmol l(-1) h(-1)) compared to succinate (8.8 C mmol
      l(-1) h(-1)) and acetate (4.3 C mmol l(-1) h(-1)). Acetate triggered an
      inhibition of cellular metabolism, which resulted in 2-h long growth arrest after
      its addition to the steady-state culture. The influence of the nitrogen source
      was investigated in an aerobic cultivation on a mixture of ammonium and nitrate
      as limiting nitrogen sources and citrate as non-limiting carbon source. When
      ammonia and nitrate were pulsed to the steady-state culture, they were mainly
      assimilated into biomass with a maximum uptake rate of 111 and 33 mg N l(-1) h(
      1), respectively. Nitrate uptake was never complete as the residual concentration
      in the chemostat cultivation was 30 mg N l(-1) nitrate. A pulse of nitrite in the
      cultivation broth resulted in an inhibition of the growth but not of the primary
      metabolism, as nitrite was taken up at 38 mg N l(-1) h(-1), citrate was consumed
      and cofactors were produced continuously. In all experiments, oxygen was used as
      electron acceptor.

PMID- 11223144
TI  - Expression and purification of human recombinant GST-FGF receptor-1.
AB  - When tumors undergo the angiogenic switch, cell growth and tissue invasion is
      facilitated by the formation of new capillaries from preexisting blood vessels, a
      process known as angiogenesis. Growth factors such as vascular endothelial growth
      factor/vascular permeability factor (VEGF/VPF) and fibroblast growth factor (FGF)
      trigger the process of angiogenesis. Here we describe a protocol for the
      expression and one-step purification of human recombinant GST-FGF receptor type 1
      (FGFR-1) from Sf9 cells. This protocol allows generating an active kinase as
      indicated by its reactivity with a monoclonal antibody to phosphorylated
      tyrosine. The purified enzyme displays a specific activity of 1.2 x 10(4) pmol
      mg(-1) min(-1), which is in the range of activities reported for homogeneously
      purified recombinant kinases. We have employed a number of compounds to show that
      the GST-FGFR-1 preparation is suitable to the identification of tyrosine kinase
      inhibitors. Considering that inhibitors of angiogenesis may represent an
      attractive tool in therapeutic strategies targeting invasive metastatic tumors
      the results presented here, along with available data on the structure of the ATP
      binding pocket of FGFR-1, should facilitate the rational design of specific FGFR
      1 inhibitory compounds.

PMID- 11223145
TI  - Optimization of the high-level production of Rhizopus oryzae lipase in Pichia
      pastoris.
AB  - The lipases of the Rhizopus species family are important and versatile enzymes
      that are mainly used in fat and oil modification due to their strong 1,3
      regiospecificity. Inexpensive synthetic medium was used for the production of
      Rhizopus oryzae lipase in the methylotrophic yeast Pichia pastoris. Methanol
      accumulation inside the bioreactor has previously been shown to negatively
      influence the production level. Three different methanol fed-batch strategies for
      maintaining the methanol concentration within optimal limits have been assayed in
      high-density cultures. One methanol feeding strategy, which is based on the
      monitoring of the methanol concentration by gas chromatography, resulted in a 2.5
      fold higher productivity compared to an initial cultivation, where the feeding
      rate was adjusted according to the dissolved oxygen concentration (DO) in the
      supernatant. Finally, productivity could be further increased by introducing a
      transition phase that involved the simultaneous feeding of glycerol and methanol
      followed by a single methanol feed. This optimized strategy resulted in the
      highest productivity (12888 U l(-1) h(-1)), which is 13.6-fold higher than the DO
      based strategy.

PMID- 11223147
TI  - Enhancement of fluoroscopic images with varying contrast.
AB  - A heuristic algorithm for enhancement of fluoroscopic images of varying contrast
      is proposed. The new technique aims at identifying a suitable type of enhancement
      for different locations in an image. The estimation relies on simple preliminary
      classification of image parts into one of the following types: uniform, sharp
      (with sufficient contrast), detail-containing (structure present) and unknown
      (for the cases where it is difficult to make a decision). Different smoothing
      techniques are applied locally in the different types of image parts. For those
      parts that are classified as detail-containing, probable object boundaries are
      identified and local sharpening is carried out to increase the contrast at these
      places. The adopted approach attempts to improve the quality of an image by
      reducing available noise and simultaneously increasing the contrast at probable
      object boundaries without increasing the overall dynamic range. In addition, it
      allows noise to be cleaned, that at some locations is stronger than the fine
      structure at other locations, whilst preserving the details.

PMID- 11223146
TI  - Succinylation of cyclodextrin glycosyltransferase from Thermoanaerobacter sp. 501
      enhances its transferase activity using starch as donor.
AB  - A simple modification procedure, the succinylation of amino groups, was suitable
      to increase the transferase (disproportionation) activity of cyclodextrin
      glycosyltransferase (CGTase) from Thermoanaerobacter sp. 501 using different
      linear oligosaccharides as acceptors. On the contrary, the synthesis of
      cyclodextrins (CDs), the coupling of CDs with oligosaccharides, and the
      hydrolysis of starch decreased after chemical modification. The degree of
      succinylation of amino groups (45%) was accurately determined by MALDI-TOF mass
      spectrometry. The formation of CDs under industrial conditions was analyzed for
      native and succinylated CGTases, showing similar selectivity to alpha-, beta-,
      gamma-CD. The acceptor reaction with D-glucose using soluble starch as glucosyl
      donor was studied at 60 degrees C and pH 5.5. Malto-oligosaccharides (MOS)
      production was notably higher using the semisynthetic enzyme at different ratios
      (w/w) starch:D-glucose. Thus, more than 90% of the initial starch was converted
      into MOS (G2-G7) in 48 h employing a ratio donor:acceptor 1:2 (w/w).

PMID- 11223148
TI  - Generating random series with known values of Kendall's tau.
AB  - Kendall's tau(a) offers statistical advantages to the more common Pearson's
      correlation and both are common in biomedical research. While generating random X
      Y pairs from a known population value of Pearson's correlation is
      straightforward, the process for generating random sequences for a known value of
      Kendall's tau(a) is more complicated. Algorithms are presented that yield random
      numbers from a population with a known expected tau(a). They begin with a small
      set of values that have a known tau. These values are 'grown' to produce an
      arbitrarily large population that has the same expectation as the smaller set.
      Two examples are given. One example simulated samples from a population where
      tau(a) equaled 0.33 and confidence intervals are produced. A second example
      illustrates how the algorithm can be used to provide statistical power estimates
      for research studies using Kendall's tau(a).

PMID- 11223149
TI  - Three dimensional reconstruction of coronary arteries from two views.
AB  - Geometric representation and measurements of localized lumen stenosis of coronary
      arteries are important considerations in the diagnosis of cardiovascular
      diseases. This discrete narrowing of the arteries typically impairs blood flow in
      regions of the heart, and can be present along the entire length of the artery.
      Three-dimensional (3-D) reconstruction of coronary arterial tree allows clinician
      to visualize vascular geometry. Three-dimensional representation of tree topology
      facilitates calculation of hemodynamic measurements to study myocardial
      infarction and stenosis. The 3-D arterial tree, computed from two views, can
      provide more information about the tree geometry than individual views. In this
      paper, a 3-step algorithm for 3-D reconstruction of arterial tree using two
      standard views is presented. The first step is a multi-resolution segmentation of
      the coronary vessels followed by medial-axis detection along the entire arterial
      tree for both views. In the second step, arterial trees from the two views are
      registered using medial-axis representation at the coarsest resolution level to
      obtain an initial 3-D reconstruction. This initial reconstruction at the coarsest
      level is then modified using 3-D geometrical a priori information. In the third
      step, the modified reconstruction is projected on the next higher-resolution
      segmented medial-axis representation and an updated reconstruction is obtained at
      the higher resolution. The process is iterated until the final 3-D reconstruction
      is obtained at the finest resolution level. Linear programming based constrained
      optimization method is used for registering two views at the coarse resolution.
      This is followed by a Tree-Search method for registering detailed branches at
      higher resolutions. The automated 3-D reconstruction method was evaluated on
      computer-simulated as well as human angiogram data. Results show that the
      automated 3-D reconstruction method provided good registration of computer
      simulated data. On human angiogram data, the computed 3-D reconstruction matched
      well with manual registration.

PMID- 11223150
TI  - A general algorithm for optimal sampling schedule design in nuclear medicine
      imaging.
AB  - Optimal sampling schedule (OSS) is of great interest in biomedical experiment
      design, as it can improve the physiological parameter estimation precision and
      significantly reduce the samples required. A number of well designed algorithms
      and software packages have been developed, which deal with the instantaneous
      measurements at discrete times. However, in nuclear medicine tracer kinetic
      studies, the imaging systems, such as positron emission tomography (PET) and
      single photon emission computed tomography (SPECT), take measurements (images)
      based on continuous accumulation over time intervals. In this case, the existing
      algorithms cannot be used to design OSS so as to reduce the image frame numbers.
      In this paper, a general OSS design algorithm for the accumulative measurement is
      proposed. The potential usefulness of the algorithm is demonstrated by its
      designing OSS in [18F] fluoro-2-deoxy-D-glucose (FDG) studies with PET to
      estimate the local cerebral metabolic rate of glucose. The robustness of
      parameter estimation using the OSS with respect to intra-subject and inter
      subject parameter variations is also presented.

PMID- 11223151
TI  - An object oriented fully 3D tomography visual toolkit.
AB  - In this paper we present a modern object oriented component object model (COMM) C
      + + toolkit dedicated to fully 3D cone-beam tomography. The toolkit allows the
      display and visual manipulation of analytical phantoms, projection sets and
      volumetric data through a standard Windows graphical user interface. Data
      input/output is performed using proprietary file formats but import/export of
      industry standard file formats, including raw binary, Windows bitmap and AVI,
      ACR/NEMA DICOMM 3 and NCSA HDF is available. At the time of writing built-in
      implemented data manipulators include a basic phantom ray-tracer and a Matrox
      Genesis frame grabbing facility. A COMM plug-in interface is provided for user
      defined custom backprojector algorithms: a simple Feldkamp ActiveX control,
      including source code, is provided as an example; our fast Feldkamp plug-in is
      also available.

PMID- 11223152
TI  - Implementation of a dynamic platform-independent DICOM-server.
AB  - Hospital-wide image and patient data transfer within heterogeneous hard- and
      software infrastructures can be facilitated by using standardized communication
      protocols and data formats such as digital imaging and communications in medicine
      (DICOM). Each DICOM application entity (AE) usually provides a static and fixed
      set of services according to its functionality. However, certain security
      concepts, changing demands of medical users, or restricted hardware capabilities
      may be more easily addressed by applications that dynamically provide variable
      subsets of DICOM services. In a new approach, an object-oriented DICOM server
      framework was developed that served as a basis for assembling various DICOM
      applications. These applications may be set up dynamically to offer variable
      subsets of services at runtime, similar to "plug-ins". The framework was designed
      and implemented in Java in order to provide low-cost platform-independent
      solutions. As an example, a DICOM server was implemented and tested in a clinical
      application providing access to MR and CT images through a Java/DICOM viewer.
      Data retrieval was optimized by storing parts of the image acquisition and
      patient data into a relational database.

PMID- 11223153
TI  - Three-dimensional visualization of lung blood flow heterogeneity based on
      fluorescent microsphere technique and fractal dimension: The Blood Flow Analysis
      System - BFA System.
AB  - The heterogeneity of regional pulmonary blood flow (RPBF) can be assessed by
      fractal analysis. The fractal dimension (FD) is a scale-independent measure of
      spatial heterogeneity of blood flow. The relative dispersion (RD) is often used
      to obtain the heterogeneity of RPBF but it is influenced by the resolution of
      measurement. The Blood Flow Analysis (BFA) System was developed in Delphi to
      represent the three-dimensional structure of lung blood flow and calculates
      statistics of FD, RD, spatial correlation of neighbored tissue samples and shows
      histograms of blood flows at diverse time points during different experiments.
      The BFA System reads a text file with flows, measured with fluorescent
      microsphere technique, and constructs the lung anatomy with volumetric pixels
      showing the flows with a color schema. It is possible to rotate the lungs into
      two axis (XY) and the statistics are shown with 3D graphics. The System maintains
      a database with data from various studies at same time. The BFA System was
      validated with four data sets from previous experiments. The BFA System has shown
      consistency and it is a new tool to help researchers during lung perfusion
      studies.

PMID- 11223154
TI  - Gene expression profile in Alzheimer's brain screened by molecular indexing.
AB  - Gene expression in the Alzheimer brain and normal brain was compared by molecular
      indexing, an advanced version of differential display. Using this technique, each
      gene was represented by a 3'-end cDNA fragment generated by class IIS restriction
      enzymes. The fragments were divided into 384 groups, and each group was separated
      by denaturing polyacrylamide gel electrophoresis. Comparison of gel patterns
      revealed 70 genes exhibiting marked differences in gene expression between AD and
      normal brain. A similarity search revealed 22 genes already reported, including
      those considered to be related to the pathogenesis such as G protein, G protein
      related, and mitochondrial components. Detailed analysis of one from those only
      matched to EST sequences revealed a novel protein with leucine-zipper and SH3
      binding motifs. Its expression was suppressed in a subpopulation of cortical
      pyramidal neurons in the AD brain, suggesting a possible relation to the
      pathogenesis. Thus, genome-scale analysis of gene expression of neurodegeneration
      is a potentially powerful approach to listing genes related to the pathogenesis.

PMID- 11223155
TI  - Influence of the somatostatin receptor sst2 on growth factor signal cascades in
      human glioma cells.
AB  - The somatostatin receptor subtype sst2A is highly expressed, non-mutated and
      functionally active in gliomas. After stimulation of cultivated human U343 glioma
      cells with somatostatin, octreotide (sst2-, sst3- and sst5-selective peptide
      agonist) or the sst2-selective non-peptide agonist L-054,522 multiple signal
      transduction pathways are induced: elevated cAMP levels are reduced, protein
      tyrosine phosphatases (especially SHP2) are activated and mitogen-activated
      protein kinases are inhibited. Stimulation of the phosphatases resulted in
      dephosphorylation of activated receptors for EGF and PDGF (epidermal and platelet
      derived growth factor), and as a consequence the mitogen-activated protein
      kinases ERK 1 and 2 (p42/p44) were de-phosphorylated in co-stimulation
      experiments. Furthermore, somatostatin or sst2-selective agonists reduced EGF
      stimulated expression of the AP-1 complex (c-jun/c-jun) on the transcriptional
      and translational level. These experiments show that the interaction of
      stimulatory and inhibitory receptors are important mechanisms for the regulation
      of signal cascades and gene expression.

PMID- 11223156
TI  - The small myelin-associated glycoprotein binds to tubulin and microtubules.
AB  - The myelin-associated glycoprotein (MAG) exists as two isoforms, differing only
      by their respective cytoplasmic domains, that have been suggested to function in
      the formation and maintenance of myelin. In the present study, a 50 kDa protein
      binding directly to the small MAG (S-MAG) cytoplasmic domain was detected and
      identified as tubulin, the core component of the microtubular cytoskeleton. In
      vitro, the S-MAG cytoplasmic domain slowed the polymerization rate of tubulin and
      co-purified with assembled microtubules. A significant sequence homology was
      found between the tau family tubulin-binding repeats and the carboxy-terminus of
      S-MAG. Our results indicate that S-MAG is the first member of the Ig superfamily
      that can be classified as a microtubule-associated protein, and place S-MAG in a
      dynamic structural complex that could participate in linking the axonal surface
      and the myelinating Schwann cell cytoskeleton.

PMID- 11223157
TI  - Axotomy alters neurotrophin and neurotrophin receptor mRNAs in the vagus nerve
      and nodose ganglion of the rat.
AB  - Neurotrophins and neurotrophin receptors play an important role in survival and
      growth of injured peripheral nerves. To study the injury-mediated neurotrophic
      response in autonomic nerves, we investigated changes in mRNA expression of
      neurotrophins and their receptors in the transected vagus nerve and nodose
      ganglion. Studies using in situ hybridization histochemistry showed that axotomy
      of the cervical vagus nerve resulted in increased expression of mRNAs for nerve
      growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3
      (NT-3), and for TrkA, TrkB, and TrkC receptors in non-neuronal cells at both the
      proximal and distal segments of the transected cervical vagus nerve. Moreover,
      NGF protein was increased in the distal end, and NT-3 protein was increased in
      both the proximal and the distal ends of the transected nerve 3 days after
      axotomy. No change of p75(NTR) mRNA was detected in the transected vagus nerve.
      The induction of each neurotrophin and Trk receptor mRNA was apparent within 1
      day after the axotomy and was sustained at least 14 days. By 45 days after the
      axotomy, a time when axonal reconnection with target tissue is made (integrity of
      the nerve-target connection was confirmed by the retrograde transport of
      FluoroGold from the stomach to vagal cell bodies), the levels of neurotrophin and
      Trk mRNAs in the vagus nerve declined to pre-axotomy levels. TrkA, TrkC, and
      p75(NTR) mRNA-containing vagal sensory neurons in the nodose ganglion were
      reduced in number after cervical vagotomy. Neurotrophin-mRNA-containing neurons
      were not found in the nodose ganglia from either intact or vagotomized rats. The
      axotomy-induced up-regulation of neurotrophins and Trk receptors mainly in the
      non-neuronal cells at or near the site of transection suggests that neurotrophins
      are involved in the survival and regeneration process of the vagus nerve after
      injury.

PMID- 11223159
TI  - Glatiramer acetate blocks interleukin-1-dependent nuclear factor-kappaB
      activation and RANTES expression in human U-251 MG astroglial cells.
AB  - RANTES is a basic 8-kDa polypeptide of the C-C chemokine subfamily with strong
      chemoattractant activity for T lymphocytes and monocytes/macrophages that are
      implicated in the pathogenesis of multiple sclerosis (MS) lesions. Glatiramer
      acetate is a drug recently approved for the treatment of MS. We therefore
      investigated the effect of glatiramer acetate on RANTES expression in glial cells
      in vitro. Treatment of human U-251 MG astroglial cells with glatiramer acetate
      blocks IL-1beta-induced RANTES chemokine production in a dose- and time-dependent
      manner. Glatiramer acetate also decreased steady-state levels of RANTES mRNA in
      these cells, which was attributable to reduced transcription, as assessed by
      nuclear run-on assays. In addition, we showed that NF-kappaB may be the
      transcriptional activator responsible for the IL-1beta-mediated RANTES gene
      expression in this system. Our data indicated that the IL-1beta-induced increase
      in RANTES was associated with an increase in in vitro nuclear extract binding
      activity specific for the NF-kappaB site in the promoter region of the RANTES
      gene. The increases in RANTES mRNA and protein expression were suppressed by the
      NF-kappaB inhibitors gliotoxin, isohelenin, and pyrrolidine dithiocarbamate
      (PDTC). Furthermore, we demonstrated that the increase in NF-kappaB DNA-binding
      activity was prevented by pretreatment with glatiramer acetate or the NF-kappaB
      inhibitors. Our results suggest that glatiramer acetate may inhibit IL-1beta
      stimulated RANTES expression in human glial cells by blocking NF-kappaB
      activation, thus identifying part of the molecular basis for its anti
      inflammatory and immunosuppressive effects in demyelinating diseases.

PMID- 11223158
TI  - Gonadal regulation of PrRP mRNA expression in the nucleus tractus solitarius and
      ventral and lateral reticular nuclei of the rat.
AB  - We investigated the prolactin-releasing peptide (PrRP) gene expression
      quantitatively in the rat brain and the involvement of estrogen and progesterone
      using in situ hybridization. The strongest signals were observed in the nucleus
      tractus solitarius (NTS), which showed approximately 70% of total PrRP mRNA in
      the brain. Moderate expression was observed in the ventral and lateral reticular
      nuclei (VLRN) of the medulla oblongata. PrRP mRNA signals in the hypothalamic
      ventromedial- and dorsomedial nuclei showed only 5% of total signals. The PrRP
      mRNA expression among female rats showing normal gonadal cycle and male rats
      showed that the highest levels were in female rats in proestrus. Administration
      of estrogen or progesterone after ovariectomy induced an increase in PrRP mRNA
      expression in the NTS. PrRP mRNA content in the NTS increased with the progress
      of the pregnancy and reached a peak on the 14th day, the mid-period of pregnancy,
      when plasma progesterone increases. We also observed the colocalization of PrRP
      and estrogen receptor alpha in the neurons distributed in the NTS by double
      labeling immunocytochemistry. These findings indicate that PrRP gene expression
      is regulated by gonadal steroid hormones in the medulla oblongata, and parts of
      PrRP synthesizing neurons are considered to be directly influenced by estrogen in
      the NTS.

PMID- 11223160
TI  - Dexamethasone reduces the expression of p75 neurotrophin receptor and apoptosis
      in contused spinal cord.
AB  - Apoptosis is an important cause of secondary cell death in spinal cord injury
      (SCI). SCI induces the expression of the low affinity neurotrophin receptor p75
      (p75NTR), that in the absence of the high affinity component, TrkA, can promote
      cell death by apoptosis. We therefore hypothesized that a reduction of p75NTR
      expression in SCI may increase tissue sparing and therefore improve recovery of
      function. As a tool to test our hypothesis we used the synthetic glucocorticoid
      dexamethasone (DEX) to down-regulate p75NTR expression. A standardized thoracic
      spinal cord contusion injury was produced in female rats. Laminectomized and SCI
      rats received various doses of DEX immediately after injury and the treatment was
      continued daily for 7 days. DEX, given at high doses (20 mg/kg, s.c.) but not at
      low doses (1 or 8 mg/kg) prevented the increase in p75NTR mRNA and protein in SCI
      rats, without affecting the expression of TrkA. High doses of DEX also reduced
      cellular apoptosis both in white and gray matters. This effect correlated with
      the ability of DEX to accelerate behavioral recovery of function measured by a
      combined behavioral score. These data suggest that reduction of p75NTR in SCI may
      be a therapeutic strategy to limit cell and tissue damage and therefore to
      improve recovery of function in SCI patients.

PMID- 11223161
TI  - Intravenous basic fibroblast growth factor (bFGF) decreases DNA fragmentation and
      prevents downregulation of Bcl-2 expression in the ischemic brain following
      middle cerebral artery occlusion in rats.
AB  - In previous studies, we showed that basic fibroblast growth factor (bFGF) reduced
      infarct volume when infused intravenously in animal models of focal cerebral
      ischemia. In the current study, we examined the potential mechanism of infarct
      reduction by bFGF, especially effects on apoptosis within the ischemic brain. We
      found that bFGF decreased DNA fragmentation in the ischemic hemisphere, as
      assessed by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick
      end labeling (TUNEL) histochemical methods combined with morphological criteria.
      bFGF also prevented reduction of immunoreactivity of the anti-apoptotic protein
      Bcl-2 in the ischemic hemisphere, but did not alter immunoreactivity of the pro
      apoptotic proteins Bax, Caspase-1, or Caspase-3. These changes in TUNEL
      histochemistry and Bcl-2 immunoreactivity were especially prominent in cortex at
      the borders ('penumbra') of infarcts, spared by bFGF treatment. We conclude that
      the infarct-reducing effects of bFGF may be due, in part, to prevention of
      downregulation of Bcl-2 expression and decreased apoptosis in the ischemic brain.

PMID- 11223162
TI  - Inhibition of depolarisation-evoked [(3)H]noradrenaline release from SH-SYFY
      human neuroblastoma cells by muscarinic (M1) receptors is not mediated by changes
      in [Ca(2+)].
AB  - The aim of this study was to obtain further understanding of the mechanism by
      which activation of muscarinic M(1) receptors inhibits K(+)-evoked noradrenaline
      (NA) release in the human neuroblastoma SH-SY5Y. Previous studies have found that
      muscarinic M(1) and M(3) receptors couple to the activation of phospholipase C in
      SH-SY5Y cells leading to an increase in (a) intracellular calcium ([Ca(2+)](i))
      and (b) activation of protein kinase C (PKC). This study used specific inhibitors
      of PKC and conditions which deplete Ca(2+)(i) stores to examine the role of
      protein kinase C and changes in [Ca(2+)](i) in mediating the inhibition of K(+)
      evoked NA release by muscarine. Our data show that pretreatment of SH-SY5Y cell
      layers with bisindolylmaleimide I (BIM-I) (i) failed to reverse inhibition of
      K(+)-evoked NA release by muscarine but (ii) did overcome the attenuation of
      muscarine inhibition following pretreatment with TPA. Furthermore pretreating
      cell layers with Ca(2+)-free Hepes buffered saline in the presence of
      thapsigargin, conditions which prevented muscarine induced increases in
      [Ca(2+)](i), failed to prevent inhibition of K(+)-evoked NA release by muscarine.
      The effect of muscarine on K(+)-evoked uptake of Ca(2+)(e) was examined in SH
      SY5Y cells loaded with Fura-2. Muscarine inhibited Ca(2+)(e)-uptake by decreasing
      the rate at which Ca(2+) entered SH-SY5Y cells via voltage sensitive Ca(2+)
      channels. Thus this study shows that muscarine inhibits depolarisation-evoked NA
      release by a mechanism which is not dependent on activation of PKC or release of
      Ca(2+) from internal stores.

PMID- 11223163
TI  - Clock gene expressions in the suprachiasmatic nucleus and other areas of the
      brain during rhythm splitting in CS mice.
AB  - The CS mouse is a mutant strain which displays spontaneous splitting in the
      circadian locomotor rhythm under continuous darkness. To clarify whether the
      rhythm splitting occurs in the suprachiasmatic nucleus (SCN) where the mammalian
      circadian clock is located, the circadian rhythmicities of mammalian clock genes,
      mPer1, mBMAL1 and mClock, were examined in the SCN and cerebral cortex during
      rhythm splitting. The circadian profiles of the clock genes during rhythm
      splitting were essentially the same as those observed under unsplit conditions.
      However, the mPer1 gene expression throughout the day was bimodal in the piriform
      and cingulate cortices, peaking in correspondence with two split components of
      behavioral rhythm. These results indicate that the circadian profiles of three
      clock gene expressions in the SCN are not consistent with the overt circadian
      locomotor rhythm, suggesting that the site of rhythm splitting is somewhere
      outside the SCN, or alternatively different subregions or other clock genes in
      the SCN are involved in rhythm splitting.

PMID- 11223165
TI  - Localization of the human mGluR4 gene within an epilepsy susceptibility locus(1).
AB  - The family of metabotropic glutamate receptors (mGluRs) consists of eight
      homologous G-protein coupled receptors. Several of the mGluRs, including the
      mGluR4 receptor subtype, are localized presynaptically; activation of this
      receptor induces an inhibition of neurotransmitter release from nerve terminals.
      Disruption of the mGluR4 gene in mice results in impaired motor and spatial
      learning, and alterations in seizure susceptibility. In this study, we have
      determined the structure of the human mGluR4 gene, as well as its chromosomal
      localization. A comparison of the gene structure of mGluR4 with the highly
      homologous mGluR6 receptor subtype reveals that both of the genes contain ten
      exons with similar exon/intron boundaries. A refined localization of mGluR4 was
      carried out by constructing a bacterial artificial chromosome clone contig of the
      region surrounding the gene. Thirteen sequence tagged sites (STSs) were
      identified within this contig. The gene was localized to chromosome 6 band p21.3
      by fluorescence in situ hybridization (FISH). The mapping of the mGluR4 gene
      indicates that it is approximately 1 megabases centromeric of the major
      histocompatibility complex and 5 megabase from the GABA(B)R1 gene. The mGluR4
      gene also falls within a susceptibility locus for juvenile myoclonic epilepsy
      suggesting a potential link to this form of epilepsy.

PMID- 11223164
TI  - Agonists of the retinoic acid- and retinoid X-receptors inhibit hepatocyte growth
      factor secretion and expression in U87 human astrocytoma cells.
AB  - Retinoids participate in the onset of differentiation, apoptosis and the
      inhibition of growth in a wide variety of normal and cancerous cells. Several
      recent reports have shown that hepatocyte growth factor (HGF), and its receptor,
      c-Met, are expressed at abnormally high levels in various human malignant gliomas
      and exert a strong proliferative action in an autocrine fashion. These results,
      consequently, imply that HGF and its receptor may represent a major contributor
      to the progression of such malignancies. Since astrocytomas are the most
      frequently occurring glioma, we have shown here that U87 cells - a well
      established, human astrocytoma cell line - express both HGF and c-Met, thereby
      providing a suitable astrocytic tumor model for studying the potential role of
      HGF, functioning in an autocrine mode, in astrocytic tumorigenesis. Furthermore,
      we demonstrated the expression of the retinoic acid receptor (RAR) isoforms,
      RARalpha, -beta and -gamma, as well as the retinoid x-receptor (RxR) isoforms,
      RxRalpha and -beta, by RT-PCR and western blot analysis in these cells. Since
      ligands of the RARs and RxRs are known to exert growth inhibitory effects on
      various tumor cells which include some astrocytomas, we speculated that such
      effect of retinoids might be mediated via inhibition of HGF secretion in human
      astrocytoma cells. Indeed, we have shown that the RAR agonists, all-trans
      retinoic acid (ATRA) and (E)-4-[2-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2
      naphthylenyl)-1-propenyl] benzoic acid (TTNPB), inhibited HGF secretion with half
      maximal inhibition occurring at 3.0 microM and 15 nM, respectively, as did the
      RxR agonists, 9-cis- and 13-cis retinoic acid (9cRA and 13cRA, respectively),
      which exerted half-maximal inhibitory effects at 40 and 25 nM, respectively.
      These actions of the RAR and RxR agonists appear to be exerted at the
      transcriptional level as assessed by Northern blot analysis. Taken together, our
      results show for the first time that retinoids, acting via the RAR and RxRs,
      significantly inhibit both the secretion and expression of HGF, thereby
      interrupting a potentially highly tumorigenic autocrine loop in astrocytoma
      cells.

PMID- 11223166
TI  - A spontaneous recurrent seizure-related Rattus NSF gene identified by linker
      capture subtraction.
AB  - Spontaneous recurrent seizures (SRS) are the major clinical characteristic of
      epilepsy. In this study, using a SRS-behavior test combined with linker capture
      subtraction (LCS) to identify genes altered in their expression in response to a
      single kainic acid (KA)-induced SRS at 3 weeks in the rat hippocampal formation.
      Dot blot analysis of the differentially expressed cDNA fragments with LCS showed
      the down-regulation of one cDNA related to SRS, which was designated epilepsy
      related gene 1 (ERG1). Northern blot analysis showed that ERG1 mRNA was reduced
      by KA administration with and without SRS, but more so with SRS. This
      differential expression had also been confirmed by in situ hybridization, which
      showed that ERG1 mRNA was down-regulated in the dorsal dentate granule cells
      (dDGCs) of the hippocampal formation, but remarkable up-regulated in the
      amygdalohippocampal area (AHi), posteromedial cortical amygdaloid nucleus (PMCo)
      and perirhinal cortex (PRh). The complete cDNA of ERG1 was cloned, sequenced
      (AF142097). It encodes a Rattus homologue of N-ethylmaleimide-sensitive fusion
      protein (NSF), which is an ATPase that plays a key role in mediating docking
      and/or fusion of transport vesicles in the multi-step pathways of vesicular
      transport. Sequence analysis revealed that ERG1 has high sequence similarity with
      the cDNA of the Mus musculus suppressor of K(+) transport growth defect (SKD2), N
      ethylmaleimide(NEM)-sensitive fusion protein of Chinese hamster and human NEM
      sensitive factor (HSU03985).

PMID- 11223167
TI  - Cloning of dopamine, norepinephrine and serotonin transporters from monkey brain:
      relevance to cocaine sensitivity.
AB  - We used RT-PCR to clone monoamine transporters from Macaca mulatta, Macaca
      fasicularis and Saimiri sciureus (dopamine transporter; DAT) and Macaca mulatta
      (norepinephrine transporter; NET and serotonin transporter; SERT). Monkey DAT,
      NET and SERT proteins were >98% homologous to human and, when expressed in HEK
      293 cells, displayed drug affinities and uptake kinetics that were highly
      correlated with monkey brain or human monoamine transporters. In contrast to
      reports of other species, we discovered double (leucine for phenylalanine 143 and
      arginine for glutamine 509; Variant I) and single (proline for leucine 355;
      Variant II) amino acid variants of DAT. Variant I displayed dopamine transport
      kinetics and binding affinities for various DAT blockers (including cocaine)
      versus [3H] CFT (WIN 35, 428) that were identical to wild-type DAT (n=7 drugs;
      r(2)=0.991). However, we detected a six-fold difference in the affinity of
      cocaine versus [3H] cocaine between Variant I (IC(50): 488+/-102 nM, SEM, n=3)
      and wild-type DAT (IC(50): 79+/-8.2 nM, n=3, P<0.05). Variant II was localized
      intracellularly in HEK-293 cells, as detected by confocal microscopy, and had
      very low levels of binding and dopamine transport. Also discovered was a novel
      exon 5 splice variant of NET that displayed very low levels of transport and did
      not bind cocaine. With NetPhos analysis, we detected a number of highly conserved
      putative phosphorylation sites on extracellular as well as intracellular loops of
      the DAT, NET, and SERT, which may be functional for internalized transporters.
      The homology and functional similarity of human and monkey monoamine transporters
      further support the value of primates in investigating the role of monoamine
      transporters in substance abuse mechanisms, neuropsychiatric disorders and
      development of diagnostic and therapeutic agents.

PMID- 11223168
TI  - Cytochrome b(5) plays a key role in human microsomal chromium(VI) reduction.
AB  - The reduction of chromium(VI) to Cr(III) results in the formation of reactive
      intermediates that contribute to the cytotoxicity, genotoxicity, and
      carcinogenicity of Cr(VI)-containing compounds. Previous studies suggest that
      human microsomal Cr(VI) reduction likely proceeds through cytochrome b(5). In
      order to better understand Cr(VI) toxicity in humans, the role of cytochrome b(5)
      in combination with P450 reductase was examined in the reductive transformation
      of Cr(VI). Proteoliposomes containing human recombinant cytochrome b(5) and P450
      reductase were constructed. The ability of P450 reductase to mediate efficient
      electron transfer from NADPH to cytochrome b(5) was confirmed by spectral
      analysis. The NADPH-dependent Cr(VI) reduction rate mediated by proteoliposomes
      was then compared to that of human microsomes. When these rates were normalized
      to equivalent cytochrome b(5) concentrations, the NADPH-dependent Cr(VI)
      reduction rates mediated by human microsomes were essentially identical to those
      for proteoliposomes containing cytochrome b(5) plus P450 reductase.
      Proteoliposomes containing only P450 reductase or cytochrome b(5) exhibited poor
      Cr(VI) reducing capabilities. Since it had been previously shown that trace
      amounts of iron (Fe) could dramatically stimulate microsomal Cr(VI) reduction,
      the ability of Fe to stimulate Cr(VI) reduction by proteoliposomes was examined.
      Both ferric chloride (FeCl(3)) and ferric adenosine-5'-diphosphate (FeADP) were
      shown to stimulate Cr(VI) reduction; this stimulation could be abolished by the
      addition of deferoxamine, a specific Fe(III) chelator. The NADPH-dependent
      reduction rates of various ferric complexes by proteoliposomes were sufficient to
      account for the increased Cr(VI) reduction rates seen with the addition of
      FeCl(3) or FeADP. Cr(V) was detected by electron paramagnetic resonance (EPR)
      spectroscopy as a transient intermediate formed during NADPH-dependent Cr(VI)
      reduction mediated by proteoliposomes containing cytochrome b(5) and P450
      reductase. Overall, cytochrome b(5) in combination with P450 reductase can
      account for the majority of the NADPH-dependent Cr(VI) reduction seen with human
      microsomes.

PMID- 11223169
TI  - Cytotoxicity of derivatives from dehydrocrotonin on V79 cells and Escherichia
      coli.
AB  - New derivatives from dehydrocrotonin (DHC, compound I), with the same anti
      ulcerogenic properties but less toxicity were synthesised by reducing the
      cyclohexenone moiety of DHC with NaBH(4) (compound II), by reducing the
      cyclohexenone and lactone moieties with LiAlH(4) (compound III) and by
      transforming the lactone moiety into an amide (compound IV) using dimethylamine.
      The cytotoxicity of these derivatives from DHC was assayed on V79 fibroblast cell
      line. Three independent endpoints for cytotoxicity were evaluated; namely, the
      nucleic acid content (NAC), tetrazolium reduction (MTT) and neutral red uptake
      (NRU). IC(50) values of 540 and 350 microM were obtained for compound II in the
      NRU and NAC tests, respectively. Compound III was less toxic than the other DHC
      derivatives (IC(50)=1800 microM) on V79 cells based on NAC assay. Compound IV
      showed an IC(50) ranging from 350 to 600 microM based on the three endpoints
      evaluated. The three compounds were less toxic on V79 cells than DHC. DHC,
      compounds II, III and IV did not change the respiration rate of Escherichia coli
      on the acute toxicity assay.

PMID- 11223171
TI  - Occurrence of verotoxin-producing Escherichia coli in dairy heifers grazing an
      irrigated pasture.
AB  - Verotoxin-producing Escherichia coli (VTEC) produce one or two toxins known as
      VT1 and VT2. These toxins have been associated with several human illnesses.
      Dairy cattle harboring VTEC represent a potential health hazard because they
      enter the food chain as ground beef. The objective of this study was to assess
      the occurrence of VTEC in dairy heifers. A total of 91 fecal samples were
      rectally collected during four periods (spring, summer, fall, and winter of 1999)
      from 23 heifers. A random sample (n=530) of potential VTEC isolates were tested
      for verotoxicity and were screened by the polymerase chain reaction (PCR) for
      presence or absence of VT1 and/or VT2 genes. Thirteen isolates from two heifers
      (from the winter collection) were verotoxic and were confirmed as E. coli. VTEC
      were only detected during winter with an occurrence rate of 9.5%. Using PCR, five
      isolates had the VT1 gene while the remaining eight had the VT2 gene. The
      sequence and expression of VT1 and VT2 genes were confirmed. No E. coli O157:H7
      was detected, but serotyping revealed that the five VT1-positive isolates were
      O26:NM (a non-motile strain of O26). The remaining eight isolates were
      untypeable. Identification of VTEC-positive cattle before slaughter is a critical
      step in any on-farm strategy to minimize the risk of beef contamination with such
      pathogens.

PMID- 11223170
TI  - Effect of diesel exhaust particles and their components on the allergen-specific
      IgE and IgG1 response in mice.
AB  - Increased antigen-specific IgE expression is a hallmark of the allergic response
      in mice. IgG1 may also be involved. Co-injection of mice with diesel exhaust
      particles (DEP) and ovalbumin three times over a 2 week period lead to a rapid
      and marked elevation of ovalbumin-specific IgE, IgG1 and also IgG2a, compared
      with ovalbumin alone. When DEP were injected 1 day before or after ovalbumin on
      each occasion, their adjuvant effect was considerably muted, suggesting that the
      adjuvant effect of DEP is short-lived, or that a physical interaction between
      ovalbumin and DEP is required. DEP were extracted with methylene chloride. Both
      the resulting core carbon particles and the organic extract enhanced ovalbumin
      specific IgE and IgG1 levels. Thus the adjuvant effect of DEP in this model is
      due both to the physical and the chemical attributes of the particles. The
      tricyclic hydrocarbons phenanthene (the most prevalent polycyclic aromatic
      hydrocarbon in DEP) and anthracene were both capable of enhancing antigen
      specific IgE and IgG1 production. The phenolic antioxidant, butylated
      hydroxyanisole, which can affect gene expression via the antioxidant responsive
      element (ARE), had a lesser effect. Two agonists for the aryl hydrocarbon
      receptor, 3-methychloranthrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin, either
      were without effect or suppressed the response, suggesting that DEP adjuvancy may
      not be mediated by this receptor.

PMID- 11223172
TI  - Diet restriction modulates lung response and survivability of rats exposed to
      ozone.
AB  - Ozone (O(3)) is a powerful oxidant component of photochemical smog polluting the
      air of urban cities. Exposure to low-level O(3) causes lung injury and increased
      morbidity of the sensitive segment of population, and exposure to high levels can
      be lethal to experimental animals. Injury from O(3) exposure is generally
      associated with free radical formation and oxidative stress. Because diet
      restriction is proposed to enhance antioxidant status, we examined whether it
      would influence the response to inhaled O(3). Twenty-four Sprague-Dawley rats, 1
      month old, weighing 150 g, were divided into two dietary regimens (12
      rats/regimen); one was freely-fed (FF), and the second was diet-restricted (DR)
      to 20% the average daily intake of the FF. After 60 days of dietary conditioning,
      the body weight of DR rats was reduced to 50% that of FF rats. Then, in one
      experiment, two groups (six rats/group), one FF and the other DR, were exposed to
      0.8+/-0.1 p.p.m. (1570+/-196 microg/m(3)) O(3), continuously for 3 days. Another
      two similar groups of rats were exposed to filtered room air and served as
      matched controls. After exposure, all rats were euthanized and the lungs analyzed
      for biochemical markers of oxidative stress. In a second experiment, 24 rats were
      divided into two groups (12 rats/group), one FF and the other DR, then exposed to
      high-level O(3) for 8 h (4 p.p.m., 7848+/-981 microg/m(3)) and the mortality
      noted during exposure and for 16 h post-exposure. Following low-level O(3),
      inhalation, greater alterations were observed in FF rats compared with DR rats.
      With high-level O(3) exposure, DR rats exhibited a much greater survivability
      compared with FF rats (90% versus 8%, respectively). These observations suggest
      that diet restriction leading to significant reduction of body weight is
      beneficial, and may play a role in the resistance to the adverse effects of O(3).

PMID- 11223173
TI  - Dehydroepiandrosterone stimulates proliferation and gene expression in MCF-7
      cells after conversion to estradiol.
AB  - Dehydroepiandrosterone (DHEA) is a mitogen for estrogen-dependent MCF-7 breast
      cancer cells. Our aims were to determine whether DHEA required conversion to
      estrogens in order to stimulate cell proliferation and estrogen-dependent gene
      expression. After incubation of cells with 100 nM DHEA for 4 days, estradiol was
      present in the medium at a concentration of approximately 200 pM. Other compounds
      identified were testosterone ( approximately 300 pM) and estrone. Significant
      stimulation of cell proliferation by 1 nM estradiol and 100 nM DHEA was observed
      after 38 h and 4 days of incubation, respectively, indicating the necessity of
      DHEA conversion. DHEA doses > or = 10 nM induced estrogen-dependent reporter gene
      expression in MCF-7 cells transfected with a luciferase reporter gene under the
      control of the estrogen response element. DHEA-dependent stimulation of
      proliferation and luciferase induction could be inhibited by the anti-estrogens
      ICI182,780 and tamoxifen, respectively, and by the aromatase inhibitor 4
      hydroxyandrostenedione. An androgenic effect of DHEA on proliferation and gene
      expression of MCF-7 cells was not observed. We conclude that conversion of DHEA
      to estrogens, particularly estradiol, is required to exert a mitogenic response.

PMID- 11223174
TI  - Specific inhibition by hGRB10zeta of insulin-induced glycogen synthase
      activation: evidence for a novel signaling pathway.
AB  - Grb10 is a member of a family of adapter proteins that binds to tyrosine
      phosphorylated receptors including the insulin receptor kinase (IRK). In this
      study recombinant adenovirus was used to over-express hGrb10zeta, a new Grb10
      isoform, in primary rat hepatocytes and the consequences for insulin signaling
      were evaluated. Over-expression of hGrb10zeta resulted in 50% inhibition of
      insulin-stimulated IRK autophosphorylation and activation. Analysis of downstream
      events showed that hGrb10zeta over-expression specifically inhibits insulin
      stimulated glycogen synthase (GS) activity and glycogen synthesis without
      affecting insulin-induced IRS1/2 phosphorylation, PI3-kinase activation, insulin
      like growth factor binding protein-1 (IGFBP-1) mRNA expression, and ERK1/2 MAP
      kinase activity. The classical pathway from PI3-kinase through Akt-PKB/GSK-3
      leading to GS activation by insulin was also not affected by hGrb10zeta over
      expression. These results indicate that hGrb10zeta inhibits a novel and presently
      unidentified insulin signaling pathway leading to GS activation in liver.

PMID- 11223175
TI  - Biochemical characterization and expression analysis of the Xenopus laevis
      corticotropin-releasing hormone binding protein.
AB  - Corticotropin-releasing hormone (CRH) plays a key role in the regulation of
      responses to stress. The presence of a high affinity binding protein for CRH (CRH
      BP) has been reported in mammals. We have characterized the biochemical
      properties and expression of CRH-BP in the South African clawed frog, Xenopus
      laevis. Apparent inhibition constants (K(i[app])) for different ligands were
      determined by competitive binding assay. Xenopus CRH-BP (xCRH-BP) exhibited a
      high affinity for xCRH (K(i[app])=1.08 nM) and sauvagine (1.36 nM). Similar to
      rodent and human CRH-BPs, the frog protein binds urotensin I and urocortin with
      high affinity, and ovine CRH with low affinity. RT-PCR analysis showed that xCRH
      BP is expressed in brain, pituitary, liver, tail, and intestine. Brain xCRH-BP
      mRNA is expressed at a relatively constant level throughout metamorphosis and
      increases slightly in the metamorphic frog. By contrast, the gene is strongly
      upregulated in the tail at metamorphic climax. Thus, regulation of xCRH-BP gene
      expression is tissue specific. Because xCRH-BP binds CRH-like peptides with high
      affinity the protein may regulated, the bioavailability of CRH in amphibia as it
      does in mammals.

PMID- 11223177
TI  - Antecedent protein restriction and high-fat feeding interactively sensitise the
      leptin response to elevated insulin.
AB  - Using a rat model of moderate (8 vs. 20% protein) isocaloric protein restriction
      initiated in early life (low protein, LP), we examined the possible basis for the
      association between impaired early growth and elevated leptin levels in later
      life in man by examining the acute leptin response to insulin and its
      relationship with glucose utilisation. We placed subsets of LP rats on a high
      saturated-fat (HF) diet containing 20% protein for 4 weeks (LP-4HF) or 8 weeks
      (LP-8HF), making comparison with age-matched control (C) groups (C, C-4HF, C
      8HF). At ambient insulin concentrations, LP was not associated with altered
      leptinaemia compared with C, despite a more active lipolytic programme as
      inferred from increased adipocyte sensitivity to norepinephrine. HF feeding led
      to insulin resistance with respect to whole-body glucose disposal (R(d))
      (measured using [3-(3)H] glucose at steady state) in both LP and C in vivo and
      impaired suppression of agonist-stimulated lipolysis by insulin in LP but not C
      in vitro. Whereas insulin infusion for 2 h (while maintaining euglycaemia) only
      modestly increased plasma leptin levels in vivo in C, C-4HF, C-8HF and LP groups,
      the leptin response to insulin was greatly enhanced in the HF-fed LP groups. A
      close positive correlation (r = 0.96) existed between plasma leptin levels and
      R(d) in the C groups (viz. C, C-4HF, C-8HF) whereas a close inverse correlation
      (r = 0.95) existed between plasma leptin levels and insulin-stimulated R(d) in
      the LP groups (viz. LP, LP-4HF, LP-8HF). Glucose utilisation (estimated from 2
      deoxy-D-[1-(3)H] glucose 6-phosphate accumulation) in vivo in two intra-abdominal
      and two superficial adipose-tissue depots was consistently higher in the LP
      group. After HF feeding, glucose utilisation by the superficial adipose-tissue
      depots was threefold higher in the LP than in the C group. We conclude that
      protein restriction from conception to adulthood followed by high-fat feeding
      sensitizes the acute leptin response to insulin, an adaptation associated with
      enhanced glucose utilisation by adipose tissue. This effect is observed despite
      impaired insulin sensitivity, both at the level of whole-body glucose disposal
      and adipocyte anti-lipolysis, and increased lipolytic activity (although the
      latter is not in itself sufficient to influence the leptin response). We propose
      that associations between a low birthweight and elevated leptin concentrations in
      later life may reflect long-term modulation of adipocyte glucose handling.

PMID- 11223176
TI  - The stimulation of MAP kinase by 1,25(OH)(2)-vitamin D(3) in skeletal muscle
      cells is mediated by protein kinase C and calcium.
AB  - In previous work we have demonstrated that the steroid hormone 1,25(OH)(2)
      vitamin D(3) [1,25(OH)(2)D(3)] stimulates in skeletal muscle cells the
      phosphorylation and activity of the extracellular signal-regulated mitogen
      activated protein (MAP) kinase isoforms ERK1 and ERK2. In the present study we
      evaluated the involvement of Ca(2+) and protein kinase C (PKC) on 1,25(OH)(2)D(3)
      induced activation of MAP kinase. The hormone response was found to depend on PKC
      stimulation since it was attenuated by the PKC inhibitors calphostin C (100 nM)
      and bisindolylmaleimide I (30 nM) and PKC downregulation by prolonged treatment
      with the phorbol ester TPA (1 microM). Removal of external Ca(2+), chelation of
      intracellular Ca(2+) with BAPTA (5 microM), inhibition of phosphoinositide
      phospholipase C (PLC) by neomycin, the calmodulin antagonist fluphenazine (50
      microM) and the specific inhibitor of calmodulin kinase II, KN-62 (10 microM),
      significantly decreased 1,25(OH)(2)D(3)-activation of MAP kinase. In addition,
      the Ca(2+)-channel blocker verapamil (5 microM) suppressed hormone-induced MAP
      kinase activity in these cells. Furthermore, the Ca(2+)-mobilizing agent
      thapsigargin and the Ca(2+)-inophore A23187 paralleled the phosphorylation of MAP
      kinase observed with 1,25(OH)(2)D(3). Taken together, these results indicate that
      PKC and Ca(2+) are two upstream activators mediating the effects of
      1,25(OH)(2)D(3) on MAP kinase in skeletal muscle cells.

PMID- 11223178
TI  - Androgen receptor signalling: comparative analysis of androgen response elements
      and implication of heat-shock protein 90 and 14-3-3eta.
AB  - Androgen receptor (AR) signalling was analysed using as models the cysteine-rich
      secretory protein-1 (CRISP-1) and CRISP-3 gene promoters, which are
      differentially regulated by androgen in vivo and contain multiple potential
      androgen response elements. Using electrophoretic mobility shift assay, we
      identified several elements with differing affinities for the AR at positions 
      3706, -1270, -1253 and -350 of the CRISP-1 promoter and at positions -369 and 
      349 of the CRISP-3 promoter. The strongest binding was observed for the -1253
      element of CRISP-1. In transactivation assays using a PC-3 cell line stably
      transfected with the AR (PC-3/AR), the -1253 element placed as two or four copies
      upstream of the TK minimal promoter yielded a strong induction of luciferase
      reporter gene activity in the presence of the androgen methyltrienolone (R1881).
      In the context of the CRISP promoters a 2-fold induction by R1881 was measured
      for the CRISP-3 upstream region whereas only limited effects were noted for the
      CRISP-1 upstream region. The androgenic stimulation of the p(-1253 ARE)(4x)-TK
      luciferase reporter construct was dose-dependently inhibited by geldanamycin and
      radicicol, two compounds that selectively interact with the chaperone protein,
      heat-shock protein 90. Cotransfection with an expression vector for the 14-3-3eta
      protein markedly enhanced the androgen-dependent stimulation. These results
      emphasize the influence of promoter context on androgen regulation and the
      importance of AR-associated proteins.

PMID- 11223179
TI  - The vitellogenin gene of the mosquito Aedes aegypti is a direct target of
      ecdysteroid receptor.
AB  - In the female mosquito Aedes aegypti, vitellogenin (Vg), the major YPP, is
      activated by 20-hydroxyecdysone (20E) at the transcriptional level. We used cell
      transfection assays in the Drosophila S2 cells to investigate whether 20E acts
      directly on the Vg gene via its functional receptor, the heterodimer composed of
      the ecdysteroid receptor (EcR) and the ultraspiracle (USP) proteins. We
      demonstrated that the Vg 5'-regulatory region contains a functional ecdysteroid
      responsive element (VgEcRE1) that is necessary to confer responsiveness to 20E.
      VgEcRE binds directly to EcR-USP produced in vitro and extracted from the
      vitellogenic fat body nuclei. The binding intensity of the EcR-USP-EcRE1 complex
      from nuclear extracts corresponds to the levels of ecdysteroids and of the Vg
      transcript during the vitellogenic cycle. Given the modest level of 20E-dependent
      activation, it is likely that the EcR-USP receptor acts synergistically with
      other transcription factors to bring about the high level of Vg gene expression.

PMID- 11223180
TI  - Differential effects of agonists of aldosterone secretion on steroidogenic acute
      regulatory phosphorylation.
AB  - The steroidogenic acute regulatory (StAR) protein mediates cholesterol transport
      within the mitochondria, and its phosphorylation is believed to be required for
      steroidogenesis. Increased extracellular potassium concentrations (K(+)),
      angiotensin II (AngII), and adrenocorticotropic hormone (ACTH) induce aldosterone
      secretion from bovine adrenal glomerulosa cells. We hypothesized that, although
      these agonists act via different signaling pathways, StAR phosphorylation should
      be common to their action. We studied the effects of K(+), AngII, and ACTH, at
      concentrations that yield comparable secretory responses, on StAR
      phosphorylation. All three agents induced significant increases in StAR
      phosphorylation although the response to ACTH was less than that of AngII and
      K(+). In cells stimulated with the protein kinase C (PKC) agonist 12
      tetradecanoylphorbol 13-acetate (TPA), the Ca(2+) channel agonist BAY K8644, and
      the adenylate cyclase agonist forskolin, TPA caused a small but statistically
      significant increase in StAR phosphorylation while BAY K8644 and forskolin had no
      significant effect. Interestingly, the combination of TPA and BAY K8644 produced
      a larger increase in StAR phosphorylation than the agents alone. We conclude that
      in cultured bovine adrenal glomerulosa cells the PKC signaling pathway is most
      effective at inducing StAR phosphorylation but that there is no simple
      correlation between this event and aldosterone production.

PMID- 11223181
TI  - Mechanisms involved in the homologous down-regulation of transcription of the
      follicle-stimulating hormone receptor gene in Sertoli cells.
AB  - The action of follicle-stimulating hormone (FSH) in spermatogenesis is regulated
      at a fundamental level by controlling the number of competent receptors present
      at the surface of Sertoli cells. By controlling the number of receptors, the cell
      is able to modulate the timing and magnitude of subsequent signal transduction in
      response to FSH. One mechanism of control is the down-regulation of the steady
      state levels of the FSH receptor gene after exposure to FSH or agents that
      stimulate or prolong the cAMP signal transduction cascade (homologous down
      regulation) in Sertoli cells. The goals of this study were to examine possible
      mechanisms involved in the down-regulation of mRNA levels of this gene. Analysis
      of transcription and processing by a PCR-based assay showed that treatment of
      Sertoli cells with FSH caused at least a 50% reduction of hnRNA for the FSH
      receptor gene. Reporter genes controlled by 5' flanking sequences of the FSH
      receptor gene that were transiently transfected into Sertoli cells were not down
      regulated. In electrophoretic mobility shift assays (EMSA), cAMP-inducible
      nuclear protein complex containing c-Fos formed on the activator protein-1/cAMP
      responsive element-like site located at -216 to -210 in the promoter of the rat
      FSH receptor gene. We concluded from this study that there was no evidence for
      the putative role of ICER in the down-regulation of the FSH receptor promoter. In
      addition, the FSH-induced down-regulation of the transcription of the FSH
      receptor gene in Sertoli cells was prevented by the treatment of Sertoli cells
      with trichostatin A prior to the addition of FSH. This experiment coupled with
      other observations suggested that the down-regulation may be mediated by changes
      in chromatin structure.

PMID- 11223182
TI  - Analysis of in vitro interactions of protein tyrosine phosphatase 1B with insulin
      receptors.
AB  - One strategy to treat the insulin resistance that is central to type II diabetes
      mellitus may be to maintain insulin receptors (IR) in the active (tyrosine
      phosphorylated) form. Because protein tyrosine phosphatase 1B (PTP1B) binds and
      subsequently dephosphorylates IR, inhibitors of PTP1B-IR binding are potential
      insulin 'sensitizers.' A Scintillation Proximity Assay (SPA) was developed to
      characterize and quantitate PTP1B-IR binding. Human IR were solubilized and
      captured on wheat germ agglutinin (WGA)-coated SPA beads. Subsequent binding of
      human, catalytically inactive [35S] PTP1B Cys(215)/Ser (PTP1B(C215S)) to the
      lectin-anchored IR results in scintillation from the SPA beads that can be
      quantitated. Binding of PTP1B to IR was pH- and divalent cation-sensitive. Ca(2+)
      and Mn(2+), but not Mg(2+), dramatically attenuated the loss of PTP1B-IR binding
      observed when pH was raised from 6.2 to 7.8. PTP1B binding to IR from insulin
      stimulated cells was much greater than to IR from unstimulated cells and was
      inhibited by either an antiphosphotyrosine antibody or treatment of IR with
      alkaline phosphatase, suggesting that tyrosine phosphorylation of IR is required
      for PTP1B binding. Phosphopeptides modeled after various IR phosphotyrosine
      domains each only partially inhibited PTP1B-IR binding, indicating that multiple
      domains of IR are likely involved in binding PTP1B. However, competitive
      displacement of [35S]PTP1B(C215S) by PTP1B(C215S) fitted best to a single binding
      site with a K(d) in the range 100-1000 nM, depending upon pH and divalent
      cations. PNU-200898, a potent and selective inhibitor of PTP1B whose orientation
      in the active site of PTP1B has been solved, competitively inhibited catalysis
      and PTP1B-IR binding with equal potency. The results of this novel assay for
      PTP1B-IR binding suggest that PTP1B binds preferentially to tyrosine
      phosphorylated IR through its active site and that binding may be susceptible to
      therapeutic disruption by small molecules.

PMID- 11223183
TI  - Immunohistochemical distribution of 11beta-hydroxysteroid dehydrogenase in human
      eye.
AB  - 11beta-hydroxysteroid dehydrogenase (11beta-HSD) regulates local actions of
      corticosteroids at glucocorticoid and mineralocorticoid receptors.
      Corticosteroids are thought to play important roles in ocular function. However,
      mechanisms of intraocular corticosteroid action are still unclear. Therefore, in
      this study, we examined the immunohistochemical localization of 11beta-HSD type 1
      (11beta-HSD1), 11beta-HSD type 2 (11beta-HSD2), mineralocorticoid receptor (MR)
      and glucocorticoid receptor (GR) in human ocular tissues from patients (6 months
      to 78 years of age; n = 10) retrieved from surgical pathology files. Both 11beta
      HSD2 and MR immunoreactivity was detected only in non-pigmented epithelium of the
      ciliary body, but was undetectable in cornea, lens, iris, retina, choroid and
      sclera, in all the cases examined. GR was detected in all cell types in the human
      eye. 11beta-HSD1 immunoreactivity was not detected in the human eye in this
      study. These results suggest that 11beta-HSD2 play an important role in human
      ocular mineralocorticoid action, such as the production of aqueous humor, in the
      ciliary body. The widespread expression of GR suggests that glucocorticoids may
      play an important role in the function and homeostasis of the human eye.

PMID- 11223184
TI  - Differentially expressed genes in zona reticularis cells of the human adrenal
      cortex.
AB  - The zona reticularis (ZR) cell in the human adrenal cortex is responsible for the
      secretion of dehydroepiandrosterone, but its biology, origin, and putative
      decrease in number during aging are poorly understood. In the present
      experiments, we investigated to what extent ZR and zona fasciculata (ZF) cells
      differ in patterns of gene expression. Both cell types were purified by
      microdissection from adult adrenal cortex specimens. After a brief period in
      culture, RNA was harvested from the cells and used to prepare radioactively
      labeled probes following amplification by PCR. Probes were used in hybridizations
      of arrays of cDNAs on nylon membranes (PCR products or plasmids obtained from an
      adrenal cDNA library). Analysis of hybridization intensities showed that 17 of
      the 750 genes studied differed in expression by more than 2-fold. Several genes
      expressed at higher levels in ZR cells encode components of the major
      histocompatibility complex or enzymes involved in peroxide metabolism. Members of
      the tubulin gene family were expressed at higher levels in ZF cells. Differential
      expression of four of the genes was confirmed by Northern blotting. These
      differences show that although ZR and ZF cells are similar in gene expression, ZR
      cells have a gene expression pattern related to the unique biology of this cell
      type.

PMID- 11223185
TI  - Sex steroid receptor regulation by genistein in the prepubertal rat uterus.
AB  - We evaluated the mechanism of action by the phytoestrogen genistein in the
      prepubertal rat uterus, when administered pharmacologically or physiologically.
      Female rats were injected with genistein (500 microg/g body weight), estradiol
      benzoate (EB) (500 ng/g body weight) or vehicle, dimethylsulfoxide (DMSO), on
      days 16, 18, and 20 postnatal. In 21-day-old rats, both compounds increased
      circulating estradiol and decreased progesterone concentrations. Uterine estrogen
      receptor alpha (ER-alpha) and androgen receptor (AR) proteins were reduced, and
      progesterone receptors (PR) were increased, as measured by western blot analyses.
      Immunohistochemistry for ER-alpha was confirmatory. Reverse transcription
      polymerase chain reaction (RT-PCR) analyses indicated a decrease in ER-alpha, but
      not in ER-beta, PR and AR mRNA levels following genistein treatment. In
      prepubertal rats exposed perinatally to 250 mg genistein per kg AIN-76A diet or
      250 microg estradiol per kg diet, uterine ER-alpha, AR, and PR proteins were not
      altered significantly. We conclude that pharmacologic, but not physiologic
      concentrations of genistein can modulate sex steroid receptor expression in the
      rat uterus.

PMID- 11223186
TI  - Enhancer regions of ovine interferon-tau gene that confer PMA response or cell
      type specific transcription.
AB  - Interferon-tau (IFNtau), produced by the trophectoderm of peri-implantation
      conceptuses in ruminant ungulates, attenuates the uterine production of a
      luteolytic factor, prostaglandin F(2alpha), resulting in the maintenance of
      corpus luteum function. However, molecular mechanisms regulating the
      temporal/spatial expression of IFNtau gene are not clearly understood. The 5'
      upstream region of the sheep IFNtau (oIFNtau) gene was examined for its
      transcriptional regulation in two different cell types; JEG3 cells supported the
      transactivation of oIFNtau-reporter construct, but HeLa cells did not. In a
      heterologous SV40 enhancer-oIFNtau promoter or oIFNtau enhancer-SV40 promoter
      systems, elements required for such cell specific transactivation were localized
      between -654 and -555 bases, the enhancer, but not the basal promoter region of
      the oIFNtau gene. In these combinations, high degrees of transactivation were
      observed in JEG3 cells and the activity was further enhanced by the addition of
      phorbol 12-myristate 13-acetate (PMA), while those responses were absent in HeLa
      cells. To identify nucleotide sequences responsible for cell specific expression,
      transient transfection studies with sequential point mutations in the enhancer
      elements were executed. Transactivation of oIFNtau enhancer-reporter constructs
      was primarily regulated by three regions containing AP-1 site, GATA like sequence
      and site(s) unidentified. In gel mobility shift assays (GMSAs), the AP-1 site
      located in the enhancer region was recognized by nuclear extracts from both cell
      types. However, one of the GMSA probes containing GATA-like sequence exhibited
      different DNA-protein complex patterns in JEG3 and HeLa cells. Observations, in
      which the same upstream sequence behaved differently due possibly to kinds of
      nuclear factors available in these cell lines, suggest that such a sequence may
      be involved in cell specific transactivation of the oIFNtau gene. Furthermore,
      the same enhancer sequences were also recognized by nuclear extracts from sheep
      trophoblasts, suggesting that the enhancer sequences between -654 and -555 bases
      of oIFNtau gene may be functioning in vivo.

PMID- 11223187
TI  - Analysis of exonic splicing enhancers in the mouse gonadotropin-releasing hormone
      (GnRH) gene.
AB  - We have previously reported that efficient removal of the first intron (intron A)
      of gonadotropin-releasing hormone (GnRH) pre-mRNA is the prerequisite event for
      post-transcriptional regulation. In the present study, using an in vitro HeLa
      splicing system, we examined the enhancing activities of exonic elements for GnRH
      pre-mRNA splicing. While not excised by exon 2 alone, intron A was efficiently
      excised when exon 3 and/or exon 4 was combined with exon 2, suggesting the
      presence of exonic splicing enhancers (ESEs) in exons 3 and 4. Purine-rich
      sequences located in the border of exons 2 and 3 (denoted ESE3) and in exon 4
      (ESE4) revealed strong splicing enhancing activities. Mutation in ESE3 decreased
      pre-mRNA splicing, while mutation in purine-rich sequences in exon 2 did not. We
      further analyzed the functional activity of ESE4 by mutations or deletions of the
      ESE4 sequence that consists of three purine-repeats separated by two spacers and
      a putative hairpin constructing sequence. An UV cross-linking assay using the RNA
      sequence of ESE4 examined the presence of ESE4-specific binding proteins in the
      nuclear extracts from GT1 hypothalamic GnRH neurons. Collectively, this study
      indicates that a sequence context of ESE4 and its binding proteins may be
      crucially involved in enhanced GnRH pre-mRNA splicing. However, it should be
      further clarified as to which splicing factor(s) is responsible for ESE4
      dependent GnRH pre-mRNA splicing.

PMID- 11223188
TI  - Intrinsic signals in the sexually dimorphic circulating growth hormone profiles
      of the rat.
AB  - Male rats secrete growth hormone (GH) in episodic bursts every 3.5-4 h. Between
      the peaks, GH levels are undetectable. In females, GH secretory profiles are
      characterized as continuous because hormone concentrations are always measurable
      in the circulation. These gender differences in the circulating GH profiles are
      responsible, to varying degrees, for observed sexual dimorphisms ranging from
      body growth to the expression of hepatic cytochrome P450 (P450, CYP) isoforms.
      Using hypophysectomized rats in which restored gender-dependent plasma GH
      profiles were manipulated, we have investigated the importance of the interpulse
      period in the masculine episodic plasma GH profile in regulating expression
      (mRNA, protein and/or specific catalytic activity) of male-specific CYP2A2, 2C11,
      2C13 and 3A2, female-specific CYP2C12 and female-predominant CYP2A1, 2C6 and 2C7.
      We observed that some isoforms were induced or suppressed by discerning the
      length of the GH-devoid interpulse period, others responded to the pulse
      amplitudes, still others recognized the mean circulating concentrations of GH and
      some were regulated by a combination of these signals. We conclude that concealed
      in the gender-dependent circulating GH profiles are numerous intrinsic signals,
      both inductive and repressive, individually "tailored" to be recognized by each
      isoform of P450. There would appear to be no one signal in each gender-dependent
      GH profile responsible, in toto, for the characteristic sexually dimorphic
      expression of some dozen hepatic P450s in male and female rats.

PMID- 11223189
TI  - Steroidogenic acute regulatory protein expression is dependent upon post
      translational effects of cAMP-dependent protein kinase A.
AB  - Tropic hormones acutely stimulate adrenal and gonadal steroidogenesis by
      activation of the cAMP-dependent protein kinase A (PKA) signaling pathway and
      subsequent induction of Steroidogenic Acute Regulatory (StAR) protein (StAR)
      expression. We present a comparative study of StAR regulation in mouse
      adrenocortical Y1 and the derived PKA mutant Kin-8 cell lines to evaluate the PKA
      requirement for StAR expression. A parallel increase in StAR steady-state mRNA
      and protein was observed in Y1 cells. StAR mRNA was induced in 8-Br-cAMP-treated
      Kin-8 cells with maximal expression levels approx. 50% of that observed in Y1
      cells. However, a corresponding increase in StAR protein, as detected by Western
      analysis, was absent in the Kin-8 cells. A similar distribution of StAR mRNA in
      active polysome fractions was observed for both 8-Br-cAMP-treated Y1 and Kin-8
      cells, as well as a 2-fold increase in incorporation of [35S]methionine into
      StAR, which indicated translation was not blocked in Kin-8 cells. Together these
      data indicate that PKA functions at the post-translational level to regulate StAR
      expression and we propose that phosphorylation of StAR by PKA contributes to
      protein stability

PMID- 11223190
TI  - GRKO mice express an aberrant dexamethasone-binding glucocorticoid receptor, but
      are profoundly glucocorticoid resistant.
AB  - The introduction of a targeted insertion mutation into exon 2 of the gene coding
      for the glucocorticoid receptor (GR) enabled production of glucocorticoid
      receptor knock-out (GRKO) mice. GRKO mice on a C57BL/6/129sv mixed genetic
      background show a variable phenotype, with 90% of -/- mice dying at birth with
      respiratory insufficiency but 10% of mutant mice surviving to maturity. To
      investigate the possibility of residual GR expression in surviving GRKO mice we
      have measured binding of the synthetic glucocorticoid dexamethasone in tissue
      extracts from adrenalectomized mice. High affinity binding of dexamethasone in
      protein extracts of liver, kidney, lung and brain from adult GRKO mice is found
      at levels 30-60% those in wild-type mice, with heterozygotes (+/-) having
      intermediate levels. PCR and ribonuclease protection analysis showed comparable
      levels of GR mRNA on the 3' side of the gene-targeted insertional mutation in
      exon 2 of the GR gene, with almost no GR mRNA detected from exons 1 and 2 on the
      5' side of the gene-targeted insertional mutation. Western blot analysis using a
      C-terminal specific GR antibody detects a 39 kDa GR fragment in extracts from
      adult GRKO mice. Despite the evidence for expression of a ligand-binding domain
      fragment of the glucocorticoid receptor these mice are profoundly glucocorticoid
      resistant, with elevated levels of plasma ACTH and corticosterone. Thymocytes
      from adult and fetal GRKO mice are resistant to dexamethasone-induced apoptosis
      and cultured fetal hepatocytes from GRKO mice are completely refractory to
      glucocorticoid induction of the gluconeogenic enzyme glucose-6-phosphatase. Thus
      although the surviving adult homozygous GRKO mice express a dexamethasone-binding
      GR fragment, their classic target tissues remain profoundly glucocorticoid
      insensitive.

PMID- 11223191
TI  - Control of renin secretion from adrenal gland in transgenic Ren-2 and normal
      rats.
AB  - In Ren-2 rats, plasma active renin and prorenin increase following binephrectomy
      (BNx) related to increasing plasma potassium. Adrenal is the source of the
      increasing prorenin but active renin comes mainly from thymus and gut. Trophic
      influences other than potassium were tested in the present work. Angiotensin did
      not influence the post-BNx increases in plasma active or prorenin but suppressed
      resting plasma prorenin from non-adrenal, non-renal sources virtually to zero.
      ACTH and histamine had no discernible effects. Hexamethonium decreased by 50% the
      post BNx increase in prorenin but not active renin. In Sprague-Dawley and
      spontaneously hypertensive rats, low levels of active renin secretion were
      detected from adrenal but no prorenin. Thus, in anesthetized Ren-2 rats, secreted
      prorenin is from two sources, i.e. extrarenal and extra-adrenal sites readily
      suppressible with angiotensin and the adrenal that is partly suppressible by
      autonomic blockage. This may assist in identifying the origin of extra-renal
      prorenin secreted in man.

PMID- 11223194
TI  - Relationships among Sarcocystis species transmitted by New World opossums
      (Didelphis spp.).
AB  - At least three species of Sarcocystis (S. neurona, S. falcatula, S. speeri) have
      recently been shown to use opossums of the genus Didelphis as their definitive
      host. In order to evaluate the evolutionary relationships among Sarcocystis spp.
      isolates from the Americas, and to determine whether organisms representing the
      same parasite lineages are transmitted north and south of the Panamanian isthmus,
      we inferred the phylogenetic relationships from nucleotide sequence variation in
      parasites isolated from three opossum species (D. virginiana, D. albiventris, D.
      marsupialis). In particular, we used variation in the 25/396 marker to compare
      several isolates from Brazil, Argentina, and the United States to each other and
      to cloned S. neurona and S. falcatula whose morphology and host affinities have
      been defined in the laboratory. S. neurona was identified from a Brazilian D.
      albiventris, as well as from North American D. virginiana. Parasites resembling
      the Cornell isolate of S. falcatula are transmitted both south and north of the
      Panamanian isthmus by D. albiventris and D. virginiana, respectively. Distinct
      attributes at two genetic loci differentiated a Brazilian isolate of S. falcatula
      from all other known parasite lineages. We confirm S. neurona as the causative
      agent of recently reported neurologic disease in Southern sea otters, Enhydra
      lutris nereis. And we found that S. speeri could not be compared to the other
      opossum-derived Sarcocystis isolates on the basis of nucleotide variation at the
      25/396 locus. The widespread distribution of certain species of Sarcocystis may
      derive from their ability to parasitize migratory bird hosts in their
      intermediate stage.

PMID- 11223193
TI  - A review of Sarcocystis neurona and equine protozoal myeloencephalitis (EPM).
AB  - Equine protozoal myeloencephalitis (EPM) is a serious neurological disease of
      horses in the Americas. The protozoan most commonly associated with EPM is
      Sarcocystis neurona. The complete life cycle of S. neurona is unknown, including
      its natural intermediate host that harbors its sarcocyst. Opossums (Didelphis
      virginiana, Didelphis albiventris) are its definitive hosts. Horses are
      considered its aberrant hosts because only schizonts and merozoites (no
      sarcocysts) are found in horses. EPM-like disease occurs in a variety of mammals
      including cats, mink, raccoons, skunks, Pacific harbor seals, ponies, and
      Southern sea otters. Cats can act as an experimental intermediate host harboring
      the sarcocyst stage after ingesting sporocysts. This paper reviews information on
      the history, structure, life cycle, biology, pathogenesis, induction of disease
      in animals, clinical signs, diagnosis, pathology, epidemiology, and treatment of
      EPM caused by S. neurona.

PMID- 11223195
TI  - Characterization of a Sarcocystis neurona isolate from a Missouri horse with
      equine protozoal myeloencephalitis.
AB  - Little information is available about antigenic variation of Sarcocystis neurona
      isolated from horses with equine protozoal myeloencephalitis, nor is there much
      information available on the specific antibody pattern to S. neurona antigens of
      horses from different geographic regions where S. neurona isolates have been
      obtained. This communication reports on the characterization of a new S. neurona
      isolate, SN-MU1. The isolate was obtained from a 3-year old Thoroughbred that had
      asymmetrical neurological signs and localized skeletal muscle atrophy. This S.
      neurona isolate is similar to other S. neurona isolates by molecular analysis of
      the internal transcribed spacer (ITS-1) region and a random-amplified polymorphic
      DNA marker, but is phenotypically distinct from the other S. neurona isolates
      examined. Evaluation of the antibodies from the affected horse and
      immunohistochemical results suggested that antigenic variation of S. neurona can
      result in variable antibody-antigen reactivity observed in the S. neurona
      immunoblot test.

PMID- 11223197
TI  - Comparison of Sarcocystis neurona isolates derived from horse neural tissue.
AB  - Sarcocystis neurona is a protozoan parasite that can cause neurological deficits
      in infected horses. The route of transmission is by fecal-oral transfer of
      sporocysts from opossums. However, the species identity and the lifecycle are not
      completely known. In this study, Sarcocystis merozoites from eight isolates
      obtained from Michigan horses were compared to S. neurona from a California horse
      (UCD1), Sarcocystis from a grackle (Cornell), and five Sarcocystis isolates from
      feral opossums from Michigan. Comparisons were made using several techniques. SDS
      PAGE analysis with silver staining showed that Sarcocystis spp. from the eight
      horses appeared the same, but different from the grackle isolate. One Michigan
      horse isolate (MIH6) had two bands at 72 and 25kDa that were more prominent than
      the UCD1 isolate and other Michigan horse isolates. Western blot analysis showed
      that merozoites of eight of eight equine-derived isolates, and the UCD1 S.
      neurona isolate had similar bands when developed with serum or CSF of an infected
      horse. Major bands were seen at 60, 44, 30, and 16kDa. In the grackle (Cornell)
      isolate, bands were seen at 60, 44, 29, and 16kDa. DNA from merozoites of each of
      the eight equine-derived isolates and the grackle-derived isolate produced a
      334bp PCR product (Tanhauser et al., 1999). Restriction fragment length
      polymorphism (RFLP) analysis of these horse isolates showed banding patterns
      characteristic for S. neurona. The grackle (Cornell) isolate had an RFLP banding
      pattern characteristic of other S. falcatula species. Finally, electron
      microscopy examining multiple merozoites of each of these eight horse isolates
      showed similar morphology, which differed from the grackle (Cornell) isolate. We
      conclude that the eight Michigan horse isolates are S. neurona species and the
      grackle isolate is an S. falcatula species.

PMID- 11223196
TI  - Characteristics of a recent isolate of Sarcocystis neurona (SN7) from a horse and
      loss of pathogenicity of isolates SN6 and SN7 by passages in cell culture.
AB  - An isolate of Sarcocystis neurona (SN7) was obtained from the spinal cord of a
      horse with neurologic signs. The parasite was isolated in cultures of bovine
      monocytes and equine spleen cells. The organism divided by endopolygeny and
      completed at least one asexual cycle in cell cultures in 3 days. The parasite was
      maintained by subpassages in bovine monocytes for 10 months when it was found to
      be non-pathogenic to gamma interferon knockout (KO) mice. Revival of a low
      passage (10th passage) of the initial isolate stored in liquid nitrogen for 18
      months retained its pathogenicity for KO mice. Merozoites (10(6)) of the late
      passage (22nd passage) were infective to only one of four KO mice inoculated.
      Similar results were obtained with SN6 isolate of S. neurona. No differences were
      found in Western blot patterns using antigens from the low and high passage
      merozoites of the SN7 and SN6 isolates. These results suggest that prolonged
      passage in cell culture may affect the pathogenicity of some isolates of S.
      neurona.

PMID- 11223198
TI  - Direct agglutination test for the detection of antibodies to Sarcocystis neurona
      in experimentally infected animals.
AB  - Equine protozoal myeloencephalitis (EPM) is a serious neurological disease of
      horses in the Americas. The apicomplexan protozoan most commonly associated with
      EPM is Sarcocystis neurona. A direct agglutination test (SAT) was developed to
      detect antibodies to S. neurona in experimentally infected animals. Merozoites of
      the SN6 strain of S. neurona collected from cell culture were used as antigen and
      2-mercaptoethanol was added to the antigen suspension to destroy IgM antibodies
      when mixed with test sera. Mice fed sporocysts of S. speeri or S. falcatula-like
      sporocysts from opossums did not seroconvert in the SAT. The sensitivity of the
      SAT was 100% and the specificity was 90% in mice.

PMID- 11223199
TI  - Interpretation of the detection of Sarcocystis neurona antibodies in the serum of
      young horses.
AB  - Horses that are exposed to Sarcocystis neurona, a causative agent of equine
      protozoal myeloencephalitis, produce antibodies that are detectable in serum by
      western blot (WB). A positive test is indicative of exposure to the organism.
      Positive tests in young horses can be complicated by the presence of maternal
      antibodies. Passive transfer of maternal antibodies to S. neurona from
      seropositive mares to their foals was evaluated. Foals were sampled at birth
      (presuckle), at 24h of age (postsuckle), and at monthly intervals. All foals
      sampled before suckling were seronegative. Thirty-three foals from 33
      seropositive mares became seropositive with colostrum ingestion at 24h of age,
      confirming that passive transfer of S. neurona maternal antibodies occurs. Thirty
      one of the 33 foals became seronegative by 9 months of age, with a mean
      seronegative conversion time of 4.2 months. These results indicate that
      evaluation of exposure to S. neurona by WB analysis of serum may be misleading in
      young horses.

PMID- 11223200
TI  - Immunoconversion against Sarcocystis neurona in normal and dexamethasone-treated
      horses challenged with S. neurona sporocysts.
AB  - Equine protozoal myeloencephalitis is a common neurologic disease of horses in
      the Americas usually caused by Sarcocystis neurona. To date, the disease has not
      been induced in horses using characterized sporocysts from Didelphis virginiana,
      the definitive host. S. neurona sporocysts from 15 naturally infected opossums
      were fed to horses seronegative for antibodies against S. neurona. Eight horses
      were given 5x10(5) sporocysts daily for 7 days. Horses were examined for abnormal
      clinical signs, and blood and cerebrospinal fluid were harvested at intervals for
      90 days after the first day of challenge and analyzed both qualitatively (western
      blot) and quantitatively (anti-17kDa) for anti-S. neurona IgG. Four of the
      challenged horses were given dexamethasone (0.1mg/kg orally once daily) for the
      duration of the experiment. All challenged horses immunoconverted against S.
      neurona in blood within 32 days of challenge and in CSF within 61 days. There was
      a trend (P = 0.057) for horses given dexamethasone to immunoconvert earlier than
      horses that were not immunosuppressed. Anti-17kDa was detected in the CSF of all
      challenged horses by day 61. This response was statistically greater at day 32 in
      horses given dexamethasone. Control horses remained seronegative throughout the
      period in which all challenged horses converted. One control horse
      immunoconverted in blood at day 75 and in CSF at day 89. Signs of neurologic
      disease were mild to equivocal in challenged horses. Horses given dexamethasone
      had more severe signs of limb weakness than did horses not given dexamethasone;
      however, we could not determine whether these signs were due to spinal cord
      disease or to effects of systemic illness. At necropsy, mild-moderate multifocal
      gliosis and neurophagia were found histologically in the spinal cords of 7/8
      challenged horses. No organisms were seen either in routinely processed sections
      or by immunohistochemistry. Although neurologic disease comparable to naturally
      occurring equine protozoal myeloencephalitis (EPM) was not produced, we had clear
      evidence of an immune response to challenge both systemically and in the CNS.
      Broad immunosuppression with dexamethasone did not increase the severity of
      histologic changes in the CNS of challenged horses. Future work must focus on
      defining the factors that govern progression of inapparent S. neurona infection
      to EPM.

PMID- 11223201
TI  - Utilization of stress in the development of an equine model for equine protozoal
      myeloencephalitis.
AB  - Neurologic disease in horses caused by Sarcocystis neurona is difficult to
      diagnose, treat, or prevent, due to the lack of knowledge about the pathogenesis
      of the disease. This in turn is confounded by the lack of a reliable equine model
      of equine protozoal myeloencephalitis (EPM). Epidemiologic studies have
      implicated stress as a risk factor for this disease, thus, the role of transport
      stress was evaluated for incorporation into an equine model for EPM. Sporocysts
      from feral opossums were bioassayed in interferon-gamma gene knockout (KO) mice
      to determine minimum number of viable S. neurona sporocysts in the inoculum. A
      minimum of 80,000 viable S. neurona sporocysts were fed to each of the nine
      horses. A total of 12 S. neurona antibody negative horses were divided into four
      groups (1-4). Three horses (group 1) were fed sporocysts on the day of arrival at
      the study site, three horses were fed sporocysts 14 days after acclimatization
      (group 2), three horses were given sporocysts and dexamethasone 14 days after
      acclimatization (group 3) and three horses were controls (group 4). All horses
      fed sporocysts in the study developed antibodies to S. neurona in serum and
      cerebrospinal fluid (CSF) and developed clinical signs of neurologic disease. The
      most severe clinical signs were in horses in group 1 subjected to transport
      stress. The least severe neurologic signs were in horses treated with
      dexamethasone (group 3). Clinical signs improved in four horses from two
      treatment groups by the time of euthanasia (group 1, day 44; group 3, day 47).
      Post-mortem examinations, and tissues that were collected for light microscopy,
      immunohistochemistry, tissue cultures, and bioassay in KO mice, revealed no
      direct evidence of S. neurona infection. However, there were lesions compatible
      with S. neurona infection in horses. The results of this investigation suggest
      that stress can play a role in the pathogenesis of EPM. There is also evidence to
      suggest that horses in nature may clear the organism routinely, which may explain
      the relatively high number of normal horses with CSF antibodies to S. neurona
      compared to the prevalence of EPM.

PMID- 11223202
TI  - Viability of Sarcocystis neurona sporocysts and dose titration in gamma
      interferon knockout mice.
AB  - Gamma-interferon knockout mice have become the model animal used for studies on
      Sarcocystis neurona. In order to determine the viability of S. neurona sporocysts
      and to evaluate the course of the disease in these mice, sporocysts were
      collected from opossums (Didelphis virginiana), processed, and stored for varying
      periods of time. Gamma-interferon knockout mice were then inoculated orally with
      different isolates at different doses. These animals were observed daily for
      clinical signs until they died or it appeared necessary to humanely euthanize
      them. 15 of 17 (88%) mice died or showed clinical signs consistent with
      neurologic disease. The clinical neurologic symptoms observed in these mice
      appeared to be similar to those observed in horses. 15 of 17 (88%) mice were
      euthanized or dead by day 35 and organisms were observed in the brains of 13 of
      17 (77%) mice. Dose appeared not to effect clinical signs, but did effect the
      amount of time in which the course of disease was completed with some isolates.
      The minimum effective dose in this study was 500 orally inoculated sporocysts.
      Efforts to titrate to smaller doses were not attempted. Direct correlation can be
      made between molecularly characterized S. neurona sporocysts and their ability to
      cause neurologic disease in gamma-interferon knockout mice.

PMID- 11223203
TI  - Initiation of a Sarcocystis neurona expressed sequence tag (EST) sequencing
      project: a preliminary report.
AB  - To accelerate genetic and molecular characterization of Sarcocystis neurona, the
      primary causative agent of equine protozoal myeloencephalitis (EPM), a sequencing
      project has been initiated that will generate approximately 7000-8000 expressed
      sequence tags (ESTs) from this apicomplexan parasite. Poly(A)(+) RNA was isolated
      from culture-derived S. neurona merozoites, and a cDNA library was constructed in
      a unidirectional lambda phage cloning vector. Sixty phage clones were randomly
      picked from the library, and the cDNA inserts were amplified from these clones
      using the T3 and T7 primers that flank the multi-cloning site of the lambda
      vector. This analysis demonstrated that 100% (60/60) of the clones selected from
      this library contained recombinant cDNA inserts ranging in size from 0.4 to 4.0
      kilobases (kb) with an average size of 1.23kb. Single-pass sequencing from the 5'
      end of the 60 amplified cDNAs produced high-quality nucleotide sequence from 53
      of the clones. Comparison of these ESTs to the current gene databases revealed
      significant matches for 10 of the ESTs, six of which are similar to sequences
      from other Apicomplexa (i.e., Toxoplasma gondii). Importantly, none of the ESTs
      were of obvious mammalian origin, thus indicating that the cDNAs in this library
      were derived primarily from parasite mRNA and not from mRNA of the bovine
      turbinate host cells. Collectively, these data indicate that the described cDNA
      library will provide an excellent substrate for generating a portion of the ESTs
      that are planned from S. neurona. This sequencing project will greatly hasten
      gene discovery for this protozoan pathogen thereby enhancing efforts towards the
      development of improved diagnostics, treatments, and preventatives for EPM. In
      addition, the S. neurona ESTs will represent a significant contribution to the
      extensive database of sequences from the Apicomplexa. Comparative analyses of
      these apicomplexan sequences will likely offer a multitude of important
      information about the biology and evolutionary history of this phylogenetic
      grouping of parasites.

PMID- 11223204
TI  - In vitro quantitative analysis of (3)H-uracil incorporation by Sarcocytis neurona
      to determine efficacy of anti-protozoal agents.
AB  - Parasite-specific incorporation of (3)H-uracil was used to assess the replication
      of Sarcocystis neurona, a protozoal parasite associated with equine protozoal
      myeloencephalitis (EPM). Anti-protozoal drugs, pyrimethamine (0.01, 0.1 and
      1.0microg/ml PYR), sulfadiazine (5microg/ml; SDZ), sulfamethoxazole (5microg/ml;
      SMZ), diclazuril (100ng/ml; DCZ), atovaquone (0.04ng/ml; ATQ), tetracycline
      (5microg/ml; TET) and the herbicide glyphosate (1.5 and 4.5mM; GLY) were studied
      with varying S. neurona parasite densities (2x10(1)-1.2x10(6)merozoites/well). A
      microtiter plate format was used to test these compounds, and incorporation of
      (3)H-uracil was determined using a semi-automated plate harvester and liquid
      scintillation counter. When PYR, DCZ, ATQ, SMZ, SDZ, and TET were tested, the
      assay was most reliable when parasite densities were greater than 9.0x10(4)
      individual merozoites per well. When the herbicide GLY was tested, as few as 900
      individual merozoites were sufficient to demonstrate reduction in parasite
      proliferation. Of the anti-protozoal drugs commonly used to treat EPM, PYR was
      the most potent anti-S. neurona agent tested. The herbicide GLY appears to be
      more potent than all of the other compounds tested in vitro; however information
      regarding in vivo use of GLY is not available, and central nervous system
      penetration by this compound is unlikely. Incorporation of (3)H-uracil by
      replicating S. neurona is quantitative and can be used in a semi-automated assay.
      This in vitro assay is capable of high throughput screening of candidate drugs
      that may have applications in a clinical setting. Further studies using a wider
      range of drug concentrations with optimal numbers of merozoites are necessary to
      determine true potency of these agents.

PMID- 11223205
TI  - In vitro culture and synchronous release of Sarcocystis neurona merozoites from
      host cells.
AB  - The growth of Sarcocystis neurona, isolate UCD1, in continuous culture was
      examined in 10 cell lines to identify growth conditions and methods for the
      preparation of parasites free of gross host cell contamination for molecular
      studies. The unpredictable, slow release of merozoites in most cell lines
      prompted development of a method to synchronously release the parasites from
      infected host cells. The calcium ionophore A23187 at a concentration of 1 microM
      was found to release intracellular merozoites with a 40 min treatment at 37
      degrees C. The release of merozoites en masse from attached host cells allowed
      for the rapid collection of relatively pure parasites from the culture
      supernatant. This release of merozoites occurred in five different host cell
      lines. The ionophore-released parasites were highly infectious for host cells and
      appeared to be morphologically identical to naturally released merozoites, except
      that the treated merozoites had an increased number of micronemes when examined
      by electron microscopy. The ionophore did not enhance the release of sporozoites
      from sporocysts, but freezing in the presence of 5% DMSO released sporozoites
      that were infectious to bovine monocytes in in vitro culture.

PMID- 11223206
TI  - Ultrastructure of schizonts and merozoites of Sarcocystis neurona.
AB  - The ultrastructure of Sarcocystis neurona schizonts and merozoites was studied in
      specimens derived from cell culture and from the brains of infected mice.
      Schizonts and merozoites were located in the host cell cytoplasm without a
      parasitophorous vacuole at any stage of development. Merozoites divided by
      endopolygeny. Fully formed merozoites had a pellicle, numerous polysomes and
      ribosomes, smooth and rough endoplasmic reticulum, 22 subpellicular microtubules,
      9-16 dense granules, 25-75 micronemes, a plastid, a Golgi complex, 1-3
      mitochondria, a conoid, 2 apical rings, 2 polar rings, 0-6 lipid bodies, a
      nucleus and nucleolus, but no rhoptries. Most micronemes were located anterior to
      the nucleus including 1-6 micronemes in the conoid. Merozoites were either
      slender (7.3 microm x 1.7 microm) or stumpy (7.7 microm x 3.1 microm). Dense
      granules appeared to arise from the maturation face of the Golgi complex. The
      ultrastructure of in vitro derived schizonts and merozoites were similar to in
      vivo derived organisms.

PMID- 11223207
TI  - Prevalence of Neospora hughesi and Sarcocystis neurona antibodies in horses from
      various geographical locations.
AB  - Parasite-specific antibody responses to Neospora antigens were detected using the
      immunofluorescent antibody test (IFAT) and immunoblot analysis in select equine
      populations. For comparison, a naturally infected Neospora hughesi horse and an
      experimentally inoculated Neospora caninum horse were used. In addition, all
      samples were tested for antibodies to Sarcocystis neurona by immunoblot analysis.
      A total of 208 samples was evaluated. The equine populations were derived from
      five distinct geographic regions. Locations were selected based on distribution
      of Didelphis virginiana, the native North American opossum which serves as the
      definitive host for S. neurona. Only 11% of the samples that had positive titers
      of 1:100 using the IFAT were also positive for antibodies by immunoblot analysis
      in this study. Overall, there was a 2% seroprevalence for Neospora antibodies in
      all horses tested based on immunoblot analysis described. The seroprevalence for
      S. neurona antibodies varied from 0% (New Zealand and Montana) to 54% (Missouri).
      We concluded that, in testing for antibodies against Neospora antigens using
      either IFAT or immunoblot analysis, as described, positive results should not be
      attributed to the presence of antibodies to S. neurona.

PMID- 11223208
TI  - Prevalence of Sarcocystis neurona sporocysts in opossums (Didelphis virginiana)
      from rural Mississippi.
AB  - Sarcocystis species sporocysts were found in intestinal scrapings from 24 of 72
      opossums (Didelphis virginiana) from rural Mississippi. The number of sporocysts
      in each opossum varied from a few ( < 100000) to 187 million. Sporocysts from 24
      opossums were bioassayed for Sarcocystis neurona infections by feeding to gamma
      interferon knockout (KO) mice. S. neurona was detected in the brains of KO mice
      fed sporocysts from 19 opossums by immunohistochemical staining with anti-S.
      neurona specific polyclonal rabbit serum, and by in vitro culture from the brains
      of KO mice fed sporocysts. The isolates of S. neurona from opossums were
      designated SN16-OP to SN34-OP. Merozoites from 17 of 19 isolates tested at the
      25/396 locus were identical to previously described S. neurona isolates from
      horses. The high prevalence of S. neurona sparocysts in D. virginiana suggests
      that this opossum constitutes an ample reservoir of infection in the southern
      United States.

PMID- 11223209
TI  - First isolation of Sarcocystis neurona from the South American opossum, Didelphis
      albiventris, from Brazil.
AB  - Sarcocystis neurona was isolated from sporocysts from two of eight South American
      opossums, Didelphis albiventris, from Brazil. Interferon gamma gene knock out
      (KO) mice fed sporocysts from two opossums developed neurologic sarcocystosis. S.
      neurona was demonstrated in the brains of infected KO mice by immunohistochemical
      staining with anti-S. neurona antibody. The parasite was cultivated in cell
      culture and S. neurona DNA was isolated from cultured merozoites. This is the
      first report of isolation of S. neurona from Brazil and the first report from its
      new host, D. albiventris.

PMID- 11223210
TI  - Sporocyst size of isolates of Sarcocystis shed by the Virginia opossum (Didelphis
      virginiana).
AB  - The Virginia opossum (Didelphis virginiana) is a definitive host for multiple
      Sarcocystis species including Sarcocystis neurona, one of the causative agents of
      equine protozoal myeloencephalitis (EPM), a severe, neuromuscular disease of
      horses. Size and morphologic characteristics of isolates of Sarcocystis shed by
      the opossum were examined to determine if differences were useful in
      discriminating between the isolates and/or species. Collections of sporocysts
      from 17 opossums were molecularly characterized and measured using an ocular
      micrometer. The mean sporocyst size of isolates of S. neurona was 10.7 microm x
      7.0 microm, Sarcocystis falcatula 11.0 microm x 7.1 microm, Sarcocystis speeri
      12.2 microm x 8.8 microm, 1085-like isolate 10.9 microm x 6.8 microm, and 3344
      like isolate 19.4 microm x 10.5 microm. The length and width of S. speeri were
      statistically different (p < 0.05) from the sporocysts of other types. The length
      of S. neurona and S. falcatula sporocysts were statistically different (p < 0.05)
      from each other and the width of S. falcatula and 1085 differed (p < 0.05). The
      fifth sporocyst type (3344) was observed, but due to pronounced morphological
      characteristics, statistical analysis was not performed. There was no consistent
      difference between the taxa based on internal structure of the sporocyst.

PMID- 11223211
TI  - Evaluation of the shedding of Sarcocystis falcatula sporocysts in experimentally
      infected Virginia opossums (Didelphis virginiana).
AB  - Five Virginia opossums (Didelphis virginiana) were fed muscles of brown-headed
      cowbirds (Molothrus ater) containing sarcocysts of Sarcocystis falcatula.
      Shedding of sporocysts was confirmed in all five opossums by fecal flotation.
      Counts were conducted daily for 2 weeks and then biweekly until the animals were
      euthanized and necropsied. The average prepatent period was 9.8 (7-16) days. The
      number of sporocysts shed varied greatly between the opossums with maximum mean
      shedding occurring at 71.6 (26-112) days post-infection (DPI). Average sporocyst
      production was 1480 sporocysts/gram of feces (SPG). Maximum output was 37,000
      SPG. Average fecal yield in captivity was 17.5g of feces/day. Opossums shed
      25,900 sporocysts/day (average) and a maximum of 647,500 sporocysts/day. All
      opossums shed sporocysts until time of euthanasia (46-200 DPI). Histologically,
      numerous sporocysts were present in the lamina propria at necropsy, primarily in
      the proximal half of the small intestine. Sporocysts were generally in clusters
      within the lamina propria of the luminal two-thirds of the villi. Sporocysts were
      found less frequently in the epithelium. No evidence of ongoing gametogony or
      other development was evident.

PMID- 11223212
TI  - Influence of size of sporocyst inoculum upon the size and number of sarcocysts of
      Sarcocystis falcatula which develop in the brown-headed cowbird.
AB  - The influence of the number of sporocysts in the inoculum of Sarcocystis
      falcatula on the morphology of the sarcocysts has not been reported in the
      literature. To determine if there is a relationship, different number of
      sporocysts were inoculated orally into wild-caught cowbirds. After 14 weeks, the
      cowbirds were euthanised and muscle tissue was examined grossly and by histologic
      sections. Sarcocysts were compared based on the numbers which developed and their
      sizes. There was a linear increase in the number of sarcocysts as the size of the
      inoculum increased, however, the size of the sarcocysts became smaller with the
      increase in number of sporocysts inoculated.

PMID- 11223213
TI  - Development of Sarcocystis falcatula in its intermediate host, the Brown-headed
      Cowbird (Molothrus ater).
AB  - Sporocysts of Sarcocystis falcatula obtained from experimentally infected
      Virginia opossums (Didelphis virginiana) were inoculated orally to 60 wild-caught
      Brown-headed Cowbirds (Molothrus ater). Another 30 Brown-headed Cowbirds were not
      challenged and served as uninfected controls. Two inoculated and one control
      cowbird were necropsied every 2 weeks and the pectoral and thigh muscles were
      examined grossly for cyst development. Stained histologic sections of pectoral
      muscle, thigh muscle, and lung were examined by light microscopy and presence,
      density, and size of sarcocysts were determined. Sarcocysts were present by 6
      weeks post-inoculation (PI) and were still growing at 40 weeks PI. The sarcocysts
      from birds 40 weeks post-infection were infective to an opossum. The morphology
      of the sarcocyst wall by transmission electron microscopy substantiated the
      identification as S. falcatula. Lung sections were examined for the presence of
      schizonts, but were seen only at 2 weeks PI. This evaluation was complicated by
      the presence of unidentified microfilariae. These birds are migratory and the
      continued growth and development of muscle cysts would allow them to be a source
      of infection at both extremes of their geographic range, regardless of which end
      of the migration at which they were infected.

PMID- 11223214
TI  - Myocarditis and encephalitis associated with Sarcocystis neurona infection in
      raccoons (Procyon lotor).
AB  - Sarcocystis neurona associated granulomatous encephalitis was found in 2 of 84
      adult raccoons. Both raccoons also had an extensive nonsuppurative myocarditis
      and one had S. neurona schizonts and merozoites in the myocardium. Only the
      asexual stages (schizonts and merozoites) of S. neurona are found in tissues of
      naturally infected animals (horse, mink, raccoons, cats, skunk, pony, seals, sea
      otters) and since these have not been reported outside the central nervous
      system, the presence of concurrent myocarditis in raccoons with the presence of
      S. neurona in the current study is of interest. Pathologists should consider the
      possible association of S. neurona with myocardial inflammation in other S.
      neurona susceptible animals.

PMID- 11223215
TI  - Migration and development of Sarcocystis neurona in tissues of interferon gamma
      knockout mice fed sporocysts from a naturally infected opossum.
AB  - Migration and development of Sarcocystis neurona was studied in 50 gamma
      interferon knockout mice fed graded doses of S. neurona sporocysts from the
      intestine of a naturally infected opossum. Mice were examined at necropsy 1-62
      days after feeding sporocysts (DAFS). All tissue sections were reacted with anti
      S. neurona-specific polyclonal rabbit serum in an immunohistochemical (IHC) test.
      Between 1 and 3 DAFS, organisms were seen mainly in intestines. Between 4 and 11
      DAFS, organisms were seen in several visceral tissues. Beginning with 13 DAFS,
      schizonts and merozoites were present in sections of brains of all infected mice.
      All regions of the brain were parasitized but the hind brain was most severely
      affected. S. neurona was found in the spinal cord of all 10 mice examined 22-30
      DAFS. Of the 28 infected mice examined 20-62 DAFS, S. neurona was found in the
      brains of all 28, lungs of 14, hearts of 8 and eyes of 3. More organisms were
      seen in IHC-stained sections than in sections stained with hematoxylin and eosin.
      Treatment of tissues with glutaraldehyde, Karnovsky fixative, and ethylene
      diamino tetra acetic acid (EDTA, used for decalcification) did not affect
      staining of organisms by IHC.

PMID- 11223216
TI  - Sarcocystis neurona and Sarcocystis falcatula: monitoring of schizogony in cell
      culture using fluorescent nuclear labeling.
AB  - The nuclei of merozoites of Sarcocystis neurona and Sarcocystis falcatula were
      labeled with the fluorescent marker Syto21. It was shown that the marker would
      label the parasites and that they would retain the marker throughout schizogony.
      Thus, there was sufficient marker in the daughter merozoites to make them easily
      visible with fluorescence microscopy. This technique will be helpful in studying
      the developmental biology of these parasites in vitro.

PMID- 11223217
TI  - A new acyclic monoterpene glucoside from Viscum album ssp. album.
AB  - 2,6-Dimethylocta-2,7-diene-1,6-diol 6-O-[6'-O-beta-D-apiofuranosyl]-beta-D
      glucopyranoside (1) was isolated from Viscum album ssp. album.

PMID- 11223219
TI  - Antiviral activity of an acidic polysaccharides fraction extracted from Cedrela
      tubiflora leaves.
AB  - An acidic polysaccharides fraction (APS) obtained from Cedrela tubiflora leaves
      was tested for antiviral activity. This fraction inhibited the replication of HSV
      2 and VSV, while the replication of poliovirus was not affected. APS was not
      virucidal, but no cytotoxicity was present in the different concentrations of APS
      assayed.

PMID- 11223218
TI  - New antifungal constituents from Terminalia alata.
AB  - The roots of Terminalia alata yielded three new glycosides: 3,3'-di-O
      methylellagic acid 4-O-beta-D-glucopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-
      >2)-alpha-L-arabinopyranoside (1), 5,7,2'-tri-O-methylflavanone 4'-O-alpha-L
      rhamnopyranosyl-(1-->4)-beta-D-glucopyranoside (2), and 2alpha,3beta, 19beta,23
      tetrahydroxyolean-12-en-28-oic acid 3-O-beta-D-galactopyranosyl-(1-->3)-beta-D
      glucopyranoside-28-O-beta-D-glucopyranoside (3). Compounds 2 and 3 displayed
      antifungal activity.

PMID- 11223220
TI  - Two new epimeric isopavine N-oxides from Meconopsis horridula var. racemosa.
AB  - Two new epimeric isopavine N-oxides, amuresinine N-oxide A (1) and B (2), were
      isolated from Meconopsis horridula var. racemosa. Their structures were
      elucidated by spectroscopic methods.

PMID- 11223221
TI  - CNS pharmacological effects of the total alkaloidal fraction from Albizia
      inopinata leaves.
AB  - The total alkaloidal fraction of Albizia inopinata leaves (FLA) was investigated
      for its central nervous system (CNS) effects. FLA (10 mg/kg, i.p.) significantly
      reduced (45%) the locomotor activity in mice. In addition, it inhibited the
      conditioned avoidance response behavior and induced ptosis in rats. On the other
      hand, FLA did not exert significant effect on catalepsy, but potentiated the
      haloperidol-induced catalepsy. No effect was observed on sleep induced by sodium
      pentobarbital or apomorphine-induced stereotypes.

PMID- 11223222
TI  - Anti-inflammatory activity of Dalbergia sissoo leaves.
AB  - The possible anti-inflammatory activity of the 90% ethanolic extract of Dalbergia
      sissoo leaves (DSELE) was studied in different models of inflammation in rats
      after oral administration at doses of 100, 300 and 1000 mg/kg. DSELE
      significantly inhibited carrageenin, kaolin and nystatin-induced paw oedema, as
      well as the weight of granuloma induced by a cotton pellet. It also inhibited dye
      leakage in acetic acid-induced vascular permeability test in mice. DSELE was
      devoid of ulcerogenic effect on the gastric mucosa of rats in acute and chronic
      tests. In acute toxicity studies, it was found to be safe up to 10.125 g/kg, p.o.
      in the rat. It was concluded that the D. sissoo leaf extract possessed
      significant anti-inflammatory activity (in acute, sub-acute and chronic models of
      inflammation) without any side effect on gastric mucosa.

PMID- 11223223
TI  - A new oleanane glycoside from the stem bark of Albizia gummifera.
AB  - The stem bark of Albizia gummifera has yielded four triterpenes, lupeol,
      lupenone, vitalboside-A (1) and vitalboside-A 2'-methylglucuronate (2), the last
      of which appears to be novel.

PMID- 11223224
TI  - Traditional medicinal plants in Mizoram, India.
AB  - In rural societies of Mizoram, India, traditional methods of treatment are
      followed in the majority of the populace. Information on 135 plant species from
      122 genera and 65 families is presented here.

PMID- 11223225
TI  - Antibacterial activity of Barringtonia racemosa.
AB  - The antibacterial activity of the ethanol extract of Barringtonia racemosa roots,
      its chloroform soluble fraction and, a there from an isolated clerodane
      diterpenoid is reported.

PMID- 11223226
TI  - Wound healing activity of Opuntia ficus-indica.
AB  - The methanolic extract of Opuntia ficus-indica stems and its hexane, ethyl
      acetate, n-butanol and aqueous fractions were evaluated for their wound healing
      activity in rats. The extract and less polar fractions showed significant
      effects.

PMID- 11223228
TI  - Antibacterial activity of Punica granatum.
AB  - Successive petroleum ether, chloroform, methanol and water extracts of Punica
      granatum were tested (in vitro) for their antibacterial activity. The methanolic
      extract was found to be most effective against all tested microorganisms.

PMID- 11223227
TI  - Anti-inflammatory effect of (+)-pinitol.
AB  - In the carrageenin-induced paw oedema in rats, (+)-pinitol (2.5-10 mg/kg, i.p.),
      isolated from Abies pindrow leaves, showed a significant anti-inflammatory
      effect, the highest dose being comparable to phenylbutazone (100 mg/kg, i.p.).

PMID- 11223229
TI  - Antimicrobial activity of Castanopsis acuminatissima.
AB  - The methanol extracts of Castanopsis acuminatissima leaves, stem and root barks
      were partitioned (petrol, dichloromethane, ethyl acetate). Though all of the
      crude methanolic extracts and obtained fractions from them, showed a broad
      spectrum of antibacterial activity, in most cases the activity was decreased on
      fractionation. None was active against tested moulds.

PMID- 11223230
TI  - Antifungal activity of Ajuga remota.
AB  - Successive petroleum ether, dichloromethane and methanol extracts of Ajuga remota
      aerial parts were tested in vitro for their antifungal activity. The petroleum
      ether fraction was found to be the most effective against the tested pathogens.

PMID- 11223231
TI  - Effect of certain plant extracts on alpha-amylase activity.
AB  - Ethanolic extracts of Punica granatum, Mangifera indica, Boerhaavia diffusa,
      Embelia ribes, Phyllanthus maderaspatensis, and Withania somnifera, were tested
      for their effect on alpha-amylase activity (in vitro). P. granatum and M. indica
      were found to exhibit interesting alpha-amylase inhibitory activity.

PMID- 11223232
TI  - Myricetin glycosides from Licania densiflora.
AB  - Dried leaves of Licania densiflora yielded five myricetin glycosides: myricetin
      3'-methylether-3-O-glucoside (1), myricetin 3'-methylether-3-O-galactoside (2),
      myricetin 4'-methylether-3-O-rhamnoside (3), myricetin 3',5'-dimethylether-3-O
      glucoside (4), and myricetin 3',5'-dimethylether-3-O-rhamnoside (5). Their
      structures were elucidated by spectroscopic methods including mono- and bi
      dimensional NMR techniques.

PMID- 11223233
TI  - Constituents of Carapa granatum fruits.
AB  - The isolation of 6alpha,11beta-diacetoxygedunin (1) and other minor constituents
      from Carapa granatum fruits is reported.

PMID- 11223234
TI  - Triterpenes of Albizia versicolor and Albizia schimperana stem barks.
AB  - Several triterpenes were isolated from stem barks of Albizia versicolor and A.
      schimperana. Spectral data of acacic acid lactone (1) are presented.

PMID- 11223235
TI  - Triterpenoid glycoside from the roots of Terminalia alata.
AB  - The isolation and NMR spectra of the triterpenoidal glycoside,
      2alpha,3beta,19alpha-trihydroxyolean-12-en-28-oic acid 3-O-beta-D
      galactopyranosyl- (1-->3)-beta-D-glucopyranoside (1), from the roots of
      Terminalia alata are reported.

PMID- 11223236
TI  - Constituents of Asteracantha longifolia.
AB  - The isolation of two aliphatic esters and betulin from the aerial parts of
      Asteracantha longifolia is reported.

PMID- 11223237
TI  - Two amides from Piper tuberculatum fruits.
AB  - The fruits of Piper tuberculatum yielded pellitorine, N-isobutyl-2E,4E
      decadienamide (1), and piperidide-2E,4E-decadienamide (2). Their complete NMR
      analysis, based on one- and two-dimensional experiments, is reported.

PMID- 11223238
TI  - Animal mitochondrial biogenesis and function: a regulatory cross-talk between two
      genomes.
AB  - Mitochondria play a pivotal role in cell physiology, producing the cellular
      energy and other essential metabolites as well as controlling apoptosis by
      integrating numerous death signals. The biogenesis of the oxidative
      phosphorylation system (OXPHOS) depends on the coordinated expression of two
      genomes, nuclear and mitochondrial. As a consequence, the control of
      mitochondrial biogenesis and function depends on extremely complex processes that
      require a variety of well orchestrated regulatory mechanisms. It is now clear
      that in order to provide cells with the correct number of structural and
      functional differentiated mitochondria, a variety of intracellular and
      extracellular signals including hormones and environmental stimuli need to be
      integrated. During the last few years a considerable effort has been devoted to
      study the factors that regulate mtDNA replication and transcription as well as
      the expression of nuclear-encoded mitochondrial genes in physiological and
      pathological conditions. Although still in their infancy, these studies are
      starting to provide the molecular basis that will allow to understand the
      mechanisms involved in the nucleo-mitochondrial communication, a cross-talk
      essential for cell life and death.

PMID- 11223239
TI  - The dystrophin / utrophin homologues in Drosophila and in sea urchin.
AB  - The gene which is defective in Duchenne muscular dystrophy (DMD) is the largest
      known gene containing at least 79 introns, some of which are extremely large. The
      product of the gene in muscle, dystrophin, is a 427 kDa protein. The same gene
      encodes at least two additional non-muscle full length dystrophin isoforms
      transcribed from different promoters located in the 5'-end region of the gene,
      and four smaller proteins transcribed from internal promoters located further
      downstream, and lack important domains of dystrophin. Several other genes,
      encoding evolutionarily related proteins, have been identified. To study the
      evolution of the DMD gene and the significance of its various products, we have
      searched for genes encoding dystrophin-like proteins in sea urchin and in
      Drosophila. We previously reported on the characterization of a sea urchin gene
      encoding a protein which is an evolutionary homologue of Dp116, one of the small
      products of the mammalian DMD gene, and on the partial sequencing of a large
      product of the same gene. Here we describe the full-length product which shows
      strong structural similarity and sequence identity to human dystrophin and
      utrophin. We also describe a Drosophila gene closely related to the human
      dystrophin gene. Like the human gene, the Drosophila gene encodes at least three
      isoforms of full length dystrophin-like proteins (dmDLP1, dmDLP2 and dmDLP3,),
      regulated by different promoters located at the 5' end of the gene, and a smaller
      product regulated by an internal promoter (dmDp186). As in mammals, dmDp186 and
      the dmDLPs share the same C-terminal and cysteine-rich domains which are very
      similar to the corresponding domains in human dystrophin and utrophin. In
      addition, dmDp186 contains four of the spectrin-like repeats of the dmDLPs and a
      unique N-terminal region of 512 amino acids encoded by a single exon. The full
      length products and the small product have distinct patterns of expression. Thus,
      the complex structure of the dystrophin gene, encoding several large dystrophin
      like isoforms and smaller truncated products with different patterns of
      expression, existed before the divergence between the protostomes and
      deuterostomes. The conservation of this gene structure in such distantly related
      organisms, points to important distinct functions of the multiple products.

PMID- 11223240
TI  - Characterization of a MEN1 ortholog from Drosophila melanogaster.
AB  - Multiple endocrine neoplasia type 1 (MEN1) is a familial cancer syndrome
      characterized by tumors of the parathyroid, entero-pancreatic neuroendocrine and
      pituitary tissues and caused by inactivating mutations in the MEN1 gene. Menin,
      the 610-amino acid nuclear protein encoded by MEN1, binds to the transcription
      factor JunD and can repress JunD-induced transcription. We report here the
      identification of a MEN1 ortholog in Drosophila melanogaster, Menin1, that
      encodes a 763 amino acid protein sharing 46% identity with human menin.
      Additionally, 69% of the missense mutations and in-frame deletions reported in
      MEN1 patients appear in amino acid residues that are identical in the Drosophila
      and human protein, suggesting the importance of the conserved regions. Drosophila
      Menin1 gene transcripts use alternative polyadenylation sites resulting in 4.3
      and 5-kb messages. The 4.3-kb transcript appears to be largely maternal, while
      the 5-kb transcript appears mainly zygotic. The binding of Drosophila menin to
      human JunD or Drosophila Jun could not be demonstrated by the yeast two-hybrid
      analysis. The identification of the MEN1 ortholog from Drosophila melanogaster
      will provide an opportunity to utilize Drosophila genetics to enhance our
      understanding of the function of human menin.

PMID- 11223241
TI  - Herbicide resistance from a divided EPSPS protein: the split Synechocystis DnaE
      intein as an in vivo affinity domain.
AB  - We report that the N- and C-terminal splicing domains of the intein found in the
      dnaE gene of Synechocystis sp. PCC6803 (Ssp DnaE intein) are capable of
      association in vivo and in vitro, even with key splicing residues changed to
      alanine (Cys(1), Asn(159), and Cys(+1) to Ala). These studies utilized the
      herbicide resistant form of 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS)
      from Salmonella typhimurium and an Escherichia coli strain with the EPSPS gene
      deleted from its genome (E. coli strain ER2799). EPSPS was mapped to identify
      potential split sites using a facile Tn7 linker scanning procedure. Forty
      positions were found to tolerate a five amino acid insertion while 21 sites did
      not, as assayed by the rescue of growth of E. coli strain ER2799. Further
      characterization of these sites by inserting a full length Ssp DnaE intein
      identified residue 235 of EPSPS as the optimal position. The EPSPS gene was then
      divided into amino acids 1-235 and 236-427 which were fused to residues 1-123 and
      124-159 of a splicing defective Ssp DnaE intein, respectively. Expression of the
      EPSPS-intein fusions from separate DNA molecules conferred resistance to the
      herbicide glyphosate, indicating that the intein splicing domains were bringing
      the EPSPS fragments together to generate activity. As a control the split EPSPS
      without the intein-affinity domain did not allow cell growth. The use of an
      intein as an in vivo affinity domain was termed intein-mediated protein
      complementation (IPC). Intein fragment assembly was verified in vitro by
      immobilizing the C-terminal splicing domain of the Ssp DnaE intein on a resin and
      demonstrating that the N-terminal 235 amino acids of EPSPS only bound to the
      resin when fused to the N-terminal splicing domain of the Ssp DnaE intein. As
      chloroplast DNA is not transmitted by pollen in plants such as corn and soybean,
      transgene spread via pollen may be controlled in the future by expressing
      inactive gene fragments from separate DNA locations, such as the nuclear and
      chloroplast genome, and using the split intein to generate protein activity.

PMID- 11223242
TI  - Mikimopine synthase (mis) gene on pRi1724.
AB  - By determination of the nucleotide sequence adjacent to the right border of T-DNA
      of the mikimopine-type Ri plasmid (pRi1724) in Agrobacterium rhizogenes, a new
      open reading frame (ORF) encoding 318 amino acids was found. A transcript of 1.35
      kb derived from this ORF was observed in hairy roots of Ajuga reptans by northern
      blotting analysis. Including its own promoter and terminator, this ORF was
      isolated from the pRi1724 T-DNA and introduced into tobacco plants by the
      Agrobacterium-binary vector system. Since mikimopine, an opine and a stereoisomer
      of cucumopine, was accumulated in all organs of the transgenic tobacco plants,
      the new ORF was deduced to be the mikimopine synthase gene. For comparison, the
      nucleotide sequence of cucumopine synthase encoded on pRi2659 was also
      determined. No homology was found between mikimopine synthase and cucumopine
      synthase at the nucleotide, but partial homology was found at the amino acid
      level. Mikimopine synthase and cucumopine synthase produced by a protein
      expression system using E. coli catalyzed the synthesis of mikimopine and
      cucumopine from L-histidine and alpha-ketoglutaric acid, requiring NADH as a
      cofactor. These synthesized opines were identified by paper electrophoresis, TLC
      and HPLC analyses. The synthesized mikimopine or cucumopine could be degraded by
      A. rhizogenes strains harboring Ri plasmids encoding the respective catabolic
      enzyme.

PMID- 11223243
TI  - A repressor element in the 5'-untranslated region of human Pax5 exon 1A.
AB  - B-cell-specific activator protein (BSAP) encoded by the Pax5 gene plays a
      critical role during B-cell development. We have analyzed the 5'-flanking region
      plus the 5'-untranslated region (5'-UTR) of human Pax5 exon1A to clarify its
      regulatory mechanisms. Functional dissection of these regions by luciferase
      reporter assays indicated that a cluster of regulatory elements acts as a strong
      repressor between +320 and +453. Insertion of this segment between the
      heterologous simian virus 40 (SV40) promoter and the luciferase gene in both the
      sense and reverse orientation sharply reduced the luciferase activity, but
      insertion into the upstream of the SV40 promoter did not. This suggests that this
      segment must be located in the 5'-UTR to function effectively. A search through
      databases with the sequence of this segment did not reveal any known DNA binding
      factor site. Electrophoretic gel mobility shift assay (EMSA) experiments
      demonstrated that unknown factors bound to the fragment +408 to +429. Insertion
      of this fragment between the SV40 promoter and the reporter gene strongly
      suppressed the luciferase activity. Competitive EMSA indicated that the region
      between nucleotides +413 and +427 encompassed the binding site of the unknown
      factors and was hence regarded as a repressor element. Mutagenesis in this
      element significantly recovered reporter gene activity. These results suggest
      that the segment +320 to +453, especially the repressor element +413 to +427, in
      the 5'-UTR is involved in the regulation of Pax5 gene expression.

PMID- 11223244
TI  - Characterisation of a collagen gene subfamily from the potato cyst nematode
      Globodera pallida.
AB  - We have isolated two full-length genomic DNA sequences, which encode the cuticle
      collagen proteins GP-COL-1 and GP-COL-2, from the potato cyst nematode Globodera
      pallida. A third, partial collagen gene ORF termed gp-col-t(t=truncated) has also
      been isolated and appears to represent an unexpressed pseudogene. The gp-col-1
      and gp-col-2 genes both contain three short (<97 bp) introns which disrupt coding
      regions predicted to specify proteins with molecular weights of 33 and 32.7 kDa
      respectively. All three sequences show high similarity to each other and to the
      previously isolated G. pallida cDNA clone gp-col-8. The conserved pattern of
      cysteine residues and non-(Gly-X-Y)(n) region sequence similarity observed in all
      four G. pallida genes suggests that these molecules form part of the same
      subfamily of collagens. Southern analysis indicates that this subfamily is likely
      to contain further members. The G. pallida collagen sequences show striking
      similarity to twelve genes from Caenorhabditis elegans which collectively
      represent the recently classified Group 1a collagen subfamily. No data exists on
      the function of this subfamily in C. elegans. gp-col-1 and gp-col-2 are
      developmentally regulated with transcripts of both genes detected in adult virgin
      and gravid females but not in pre-parasitic second stage juveniles. A similar
      expression pattern is observed for the Group 1a collagen lemmi 5 from Meloidogyne
      incognita perhaps indicating a generic link between subfamily and function during
      the various changes in cuticular structure which accompany nematode growth and
      reproduction. Immunochemical studies indicate that the GP-COL-1 protein is
      specifically located in the hypodermis of G. pallida adult females.

PMID- 11223245
TI  - Functional screening of a retroviral peptide library for MHC class I
      presentation.
AB  - We have used retroviral vector technology to develop a method for functional
      screening of combinatorial peptide libraries expressed inside mammalian cells
      with the ultimate goal of identifying new drug targets. The method was validated
      in a library screening experiment based on antigen presentation of small
      peptides. A library encoding SIXNXEKX-peptides, where X designates randomised
      positions corresponding to major histocompatibility (MHC) class I anchor
      residues, was generated in a retroviral vector. The library was transduced into a
      population of antigen presenting cells (APCs) known to mediate MHC class I
      restricted presentation of the SIINFEKL peptide. The cellular library was
      screened by using an antigen presentation assay in which a T cell hybridoma
      recognising the MHC class I/SIINFEKL peptide complex was employed. Using this
      experimental model, we identified two positive cellular clones both encoding
      SIINFEKL peptides with identical codon usage. This number corresponded well to
      the expected frequency of SIINFEKL in the library. The lack of identification of
      other peptides capable of activating the T-hybridoma supports previous findings
      of a high degree of specificity at the level of peptide-loading of MHC-molecules.
      The result further demonstrates the potential of using combinatorial libraries
      for functional screening and selection of effector peptides stably expressed in
      mammalian cells.

PMID- 11223246
TI  - Identification and characterization of a novel human cDNA encoding a 21 kDa pRb
      associated protein.
AB  - The retinoblastoma protein (pRb) functions as a critical master regulator in cell
      cycle regulation, which is an important cell-regulatory process, through its
      interaction with various cellular proteins. Using the C-terminus of human pRb and
      the yeast two-hybrid system, a novel protein named RBP21 that contains 187 amino
      acid residues with a calculated molecular weight of 21 kDa was identified as a
      pRb-binding protein. Sequence analysis indicates that RBP21 shares homology with
      other retinoblastoma-binding proteins in the pRb-binding motif LxCxE at the C
      terminal region. In vitro specific interaction between pRb and RBP21 was
      confirmed using in vitro translation products. When overexpressed in COS-7 cells,
      RBP21 could co-immunoprecipitate with pRb. This interaction requires the LxCxE
      motif of RBP21 and the entire pocket region of pRb. Each point mutation of the
      conserved amino acid residues in pRb-binding motif of RBP21 abolished its
      specific interaction with pRb. RH mapping result showed that this novel gene was
      mapped to chromosome region 15q21.1-21.3. Northern blot analysis suggested that
      RBP21 was widely expressed in various human tissues and cancer cell lines. When
      expressed in HeLa cells as a green fluorescent protein fusion, RBP21 was
      distributed throughout the cell.

PMID- 11223247
TI  - Comparative evaluation of 5'-end-sequence quality of clones in CAP trapper and
      other full-length-cDNA libraries.
AB  - To enhance the usefulness of the laboratory mouse and to facilitate the rapid
      assay of gene functions we have been collecting the entire set of mouse full
      length cDNA by one-pass sequencing. To collect full-length cDNA clones
      efficiently, it is critical to construct high-quality cDNA libraries. In recent
      years, we have been developing a way to construct full-length cDNA libraries by
      using biotinylation of the cap structure (the 'CAP-trapper' method) coupled with
      treatment to increase reverse transcriptase efficiency at high temperature by the
      addition of trehalose. In this paper we report our evaluation of the quality of
      CAP trapper and a number of other full-length cDNA libraries, including the
      results of 5' end analysis of clones in CAP trapper and the other libraries. We
      used a procedure that compared the 5'-ends of cDNA clones with those of genes in
      the public databases. Our analysis showed that 63% of cDNA clones in CAP trapper
      libraries had sequences that were either the same length as those of equivalent
      genes in the public database or 5'-extended, and that 90% of these clones
      maintained their coding sequences. These results indicate that the CAP trapper
      library is a promising tool for collecting full-length cDNA in large-scale
      projects. Comparison of the quality of CAP trapper with that of other full-length
      cDNA libraries confirmed the value of these libraries.

PMID- 11223248
TI  - Ingestion of bacterially expressed dsRNAs can produce specific and potent genetic
      interference in Caenorhabditis elegans.
AB  - Genetic interference mediated by double-stranded RNA (RNAi) has been a valuable
      tool in the analysis of gene function in Caenorhabditis elegans. Here we report
      an efficient induction of RNAi using bacteria to deliver double-stranded RNA.
      This method makes use of bacteria that are deficient in RNaseIII, an enzyme that
      normally degrades a majority of dsRNAs in the bacterial cell. Bacteria deficient
      for RNaseIII were engineered to produce high quantities of specific dsRNA
      segments. When fed to C. elegans, such engineered bacteria were found to produce
      populations of RNAi-affected animals with phenotypes that were comparable in
      expressivity to the corresponding loss-of-function mutants. We found the method
      to be most effective in inducing RNAi for non-neuronal tissue of late larval and
      adult hermaphrodites, with decreased effectiveness in the nervous system, in
      early larval stages, and in males. Bacteria-induced RNAi phenotypes could be
      maintained over the course of several generations with continuous feeding,
      allowing for convenient assessments of the biological consequences of specific
      genetic interference and of continuous exposure to dsRNAs.

PMID- 11223249
TI  - Identification and characterization of the gene encoding human cytoplasmic
      polyadenylation element binding protein.
AB  - The maturation of human oocytes occurs in the absence of gene transcription. In
      model organisms, such as Drosophila, Xenopus, and the mouse, oocyte maturation
      and early pattern formation is mediated through the regulated translation of
      maternally derived mRNAs. The maturation-dependent stimulation of maternal mRNA
      translation is correlated with increases in poly(A) tail length, controlled
      through a process termed cytoplasmic polyadenylation. However, this mechanism of
      mRNA translational control has not been characterized in humans. In this study we
      report the cloning of a human cytoplasmic polyadenylation element binding (hCPEB)
      protein with sequence-specific RNA binding activity. Our data demonstrate that
      alternative splicing generates hCPEB mRNAs that encode proteins with a conserved
      C-terminal RNA binding domain but with different N-terminal regulatory domains.
      The hCPEB mRNA is expressed in the brain and heart as well as in immature
      oocytes, consistent with the hypothesis that cytoplasmic polyadenylation may
      regulate the translation of human mRNAs in both oocytes and somatic cells.

PMID- 11223251
TI  - Cytoplasmic retention of HIV-1 regulatory protein Vpr by protein-protein
      interaction with a novel human cytoplasmic protein VprBP.
AB  - Vpr is an HIV-1 auxiliary regulatory protein packaged in the virion. It has been
      shown to enhance the nuclear transport of the HIV-1 pre-integration complex,
      activate transcription of cellular and viral promoters, and arrest the cell cycle
      at the G2/M check-point. We previously identified a cellular protein of 180 kDa
      (RIP) that interacted with HIV-1 Vpr specifically. We now rename this cellular
      protein as Vpr-binding protein, or VprBP. In this report, we describe the cloning
      of the VprBP cDNA that encodes 1507 aa residues and is identical to the
      previously cloned cDNA KIAA0800. We demonstrate that Vpr specifically interacts
      with recombinantly expressed VprBP in vitro as well as in vivo. Furthermore, Vpr
      interacts with the cellular endogenous VprBP in the context of the HIV-1 life
      cycle. Mutational analysis of VprBP suggests that the Vpr binding domain is
      located within the C-terminal half of VprBP, which has a Pro-rich domain and
      several Phe-x-x-Phe repeats. Subcellular fractionation studies show that both the
      endogenous VprBP and the adenovirus-expressed VprBP are distributed predominantly
      in the cytoplasmic fraction. Consistent with previous reports, the adenovirus
      expressed Vpr is distributed in both the cytoplasmic and the nuclear fractions.
      However, when VprBP and Vpr are expressed together, Vpr is found almost
      exclusively in the cytoplasm. Expression of VprBP does not affect the nuclear
      transport of the adenoviral nuclear protein, pTP. VprBP expressed in insect cells
      also blocks the nuclear transport of a Vpr-GFP fusion protein, and VprBP mutants
      incapable of interacting with Vpr fail to block Vpr-GFP nuclear transport. We
      hypothesize that Vpr interaction with VprBP may cause changes in the host cell
      cytoplasm that affect HIV-1 pathogenesis as well as HIV-1 replication.

PMID- 11223252
TI  - Sequence analysis of the myosin regulatory light chain gene of the
      vestimentiferan Riftia pachyptila.
AB  - We have isolated and characterized a cDNA (DNA complementary to RNA) clone (Rf69)
      from the vestimentiferan Riftia pachyptila. The cDNA insert consists of 1169 base
      pairs. The aminoacid sequence deduced from the longest reading frame is 193
      residues in length, and clearly characterized it as a myosin regulatory light
      chain (RLC). The RLC primary structure is described in relation to its function
      in muscle contraction. The comparison with other RLCs suggested that Riftia
      myosin is probably regulated through its RLC either by phosphorylation like the
      vertebrate smooth muscle myosins, and/or by Ca2+-binding like the mollusk
      myosins. Riftia RLC possesses a N-terminal extension lacking in all other species
      besides the earthworm Lumbricus terrestris. Aminoacid sequence comparisons with a
      number of RLCs from vertebrates and invertebrates revealed a relatively high
      identity score (64%) between Riftia RLC and the homologous gene from Lumbricus.
      The relationships between the members of the myosin RLCs were examined by two
      phylogenetic methods, i.e. distance matrix and maximum parsimony. The resulting
      trees depict the grouping of the RLCs according to their role in myosin activity
      regulation. In all trees, Riftia RLC groups with RLCs that depend on Ca2+-binding
      for myosin activity regulation.

PMID- 11223253
TI  - Differential splicing of Pneumocystis carinii f. sp. carinii inosine 5'
      monophosphate dehydrogenase pre-mRNA.
AB  - Inosine 5'-monophosphate dehydrogenase (IMPDH) is a rate-limiting enzyme in
      guanine nucleotide metabolism that has drawn attention as a drug target in
      several organisms. Pneumocystis carinii f. sp. carinii IMPDH mRNA (GeneBank
      Accession No: U42442) previously identified from cultured organisms yielded a
      predicted amino acid sequence about 70 amino acids shorter at the amino terminus
      than IMPDH from other species. Recent research has shown that the amino terminal
      region is important for enzyme activity, suggesting that the previous putative P.
      carinii IMPDH might not represent full length, functional enzyme. To test this
      hypothesis, RT-PCR was performed with total RNA isolated from P. carinii f. sp.
      carinii. Three IMPDH splicing variants were found and splicing preference was
      observed: P. carinii isolated from infected rat lung contained primarily splicing
      variant one (introns two and four deleted), but organisms from spinner flask
      culture contained primarily splicing variant three (all four introns deleted).
      Importantly, splicing variant one (GeneBank Accession No: AF196975) contained an
      open reading frame for 529 amino acids, a size comparable to that of other
      eukaryotic IMPDH forms. The other variants contained the same open reading frame
      (454 amino acids) previously reported. Sequence analysis and complementation
      studies suggest variant one represents the full length, catalytically active form
      of P. carinii IMPDH. The differential splicing of the enzyme may reflect a
      mechanism by which the organism regulates the expression of IMPDH in response to
      environmental stresses.

PMID- 11223250
TI  - A survey of genes in the Atlantic salmon (Salmo salar) as identified by expressed
      sequence tags.
AB  - We describe the construction and quality analysis of six cDNA libraries from the
      liver, ovary, testis, brain, spleen and muscle tissues of adult Atlantic salmon.
      The cDNA libraries were then screened with total cDNA probes to catalogue clones
      representing the abundant and rare mRNA populations in each tissue. Subsequently,
      the 5'-terminal DNA sequences of 1152 cDNA clones, composed of 96 clones from
      each of the abundant and rare mRNA populations in the six tissues, were
      determined. Bioinformatic analysis revealed that 510 (50%) of the salmon
      expressed sequence tags (ESTs) of sufficient length showed significant homology
      to previously identified genes from salmonid and other species, while 517 (50%)
      of salmon ESTs were unidentified or novel. After accounting for multi-EST
      redundancy, the 510 identified ESTs provided DNA sequence markers for 178 salmon
      genes which are listed in terms of tissue of origin and mRNA abundance class.

PMID- 11223254
TI  - New selectable marker/auxotrophic host strain combinations for molecular genetic
      manipulation of Pichia pastoris.
AB  - We describe the isolation and characterization of three new biosynthetic genes
      ARG4, ADE1, and URA3-from the methylotrophic yeast Pichia pastoris. The predicted
      products of the genes share significant sequence similarity to their
      Saccharomyces cerevisiae counterparts, namely argininosuccinate lyase, PR
      aminoimidazolesuccinocarboxamide synthase, and orotidine-5'-phosphate
      decarboxylase, respectively. Along with the previously described HIS4 gene, each
      gene was incorporated as the yeast selectable marker into a set of shuttle
      vectors designed to express foreign genes in P. pastoris. In addition, we have
      constructed a series of host strains containing all possible combinations of
      ade1, arg4, his4, and ura3 auxotrophies to be used with these new vectors.

PMID- 11223255
TI  - Isolation and characterization of a transforming growth factor-beta Type II
      receptor cDNA from Xenopus laevis.
AB  - Transforming Growth Factor-beta (TGF-beta) and their receptors have been
      characterized from many organisms. Two TGF-beta signaling receptors called Type I
      and II have been described for various ligands of the superfamily from organisms
      ranging from Drosophila to humans. In Xenopus laevis, TGF-beta2 and 5 have been
      reported and presumably, play important roles during early development. Several
      Type I and type II receptors for many ligands of the TGF-beta superfamily except
      TGF-beta type II receptor (TbetaIIR), have been characterized in Xenopus laevis.
      A chemical cross linking experiment using iodinated TGF-beta1 and -beta5,
      revealed four specific binding proteins on XTC cells. In order to understand the
      TGF-beta involvement during Xenopus development, a TGF-beta type II receptor
      (XTbetaIIR) has been isolated from a XTC cDNA library. XTbetaIIR was a partial
      cDNA lacking a portion of the signal peptide. The sequence analysis and homology
      comparison with the human TbetaIIR revealed 67% amino acid similarity in the
      extra cellular domain, 60% similarity in the transmembrane domain and 87%
      similarity in the cytoplasmic kinase domain, suggesting that XTbetaIIR is a
      putative TGF-beta type II receptor. In addition, the consensus amino acid motif
      for serine threonine receptor kinases was also present. Further, a dominant
      negative expression construct lacking the cytoplasmic kinase domain (engineered
      with the signal peptide from human TGF-beta type II receptor), was able to
      abolish TGF-beta mediated induction of a luciferase reporter plasmid, in a
      transient cell transfection assay. This substantiates the notion that XTbetaIIR
      cDNA can act as a receptor for TGF-beta. RT-PCR analysis using RNA isolated from
      various developmental stages of Xenopus laevis revealed expression of this gene
      in all the early stages of development and in the adult organs, except in stages
      46/48.

PMID- 11223256
TI  - Cloning and expression of a nuclear encoded plastid specific 33 kDa
      ribonucleoprotein gene (33RNP) from pea that is light stimulated.
AB  - We report the cloning and sequencing of both cDNA and genomic DNA of a 33 kDa
      chloroplast ribonucleoprotein (33RNP) from pea. The analysis of the predicted
      amino acid sequence of the cDNA clone revealed that the encoded protein contains
      two RNA binding domains, including the conserved consensus ribonucleoprotein
      sequences CS-RNP1 and CS-RNP2, on the C-terminus half and the presence of a
      putative transit peptide sequence in the N-terminus region. The phylogenetic and
      multiple sequence alignment analysis of pea chloroplast RNP along with RNPs
      reported from the other plant sources revealed that the pea 33RNP is very closely
      related to Nicotiana sylvestris 31RNP and 28RNP and also to 31RNP and 28RNP of
      Arabidopsis and spinach, respectively. The pea 33RNP was expressed in Escherichia
      coli and purified to homogeneity. The in vitro import of precursor protein into
      chloroplasts confirmed that the N-terminus putative transit peptide is a bona
      fide transit peptide and 33RNP is localized in the chloroplast. The nucleic acid
      binding properties of the recombinant protein, as revealed by South-Western
      analysis, showed that 33RNP has higher binding affinity for poly (U) and oligo dT
      than for ssDNA and dsDNA. The steady state transcript level was higher in leaves
      than in roots and the expression of this gene is light stimulated. Sequence
      analysis of the genomic clone revealed that the gene contains four exons and
      three introns. We have also isolated and analyzed the 5' flanking region of the
      pea 33RNP gene.

PMID- 11223257
TI  - Characterization of a rice (Oryza sativa L.) Bowman-Birk proteinase inhibitor:
      tightly light regulated induction in response to cut, jasmonic acid, ethylene and
      protein phosphatase 2A inhibitors.
AB  - The Bowman-Birk (BB) family of proteinase inhibitors (PI), initially reported
      from legume seeds, and thereafter also from wounded alfalfa and maize leaves
      appear to be regulated in similar ways as the extensively characterized PI I and
      PI II family from dicots. Here, we report a first characterization of the
      expression profiles of a rice (Oryza sativa L. cv. Nipponbare) BBPI gene, OsBBPI,
      which is part of a multigene family as demonstrated by genomic Southern
      hybridization. OsBBPI was found to be rapidly induced in rice seedling leaf in
      response to cut, exogenous jasmonic acid (JA), and two potent protein phosphatase
      2A (PP2A) inhibitors, cantharidin (CN) and endothall (EN), in a light/dark-, time
      and dose-dependent manner; this induction was completely inhibited by
      cycloheximide (CHX), indicating a requirement for de novo protein synthesis in
      its induction. Surprisingly, dark strongly up regulated cut-, JA-, CN-, and EN
      induced OsBBPI expression, with the strongest enhancement observed with JA. A
      simultaneous application of a serine/threonine protein kinase inhibitor
      staurosporine (ST) did not affect significantly the JA-, CN-, and EN-induced
      OsBBPI transcript. Besides JA, it was found that the ethylene generator ethephon
      (ET) also had an enhancing effect on OsBBPI transcript, suggesting a direct
      effect of ethylene on OsBBPI expression. However, a simultaneous application of
      salicylic acid (SA) and abscisic acid (ABA), with JA, respectively, completely
      blocked OsBBPI gene expression, whereas kinetin (KN) was only partially
      effective. To the best of our knowledge, complete inhibition of JA-induced OsBBPI
      expression by SA is the first report in monocots, and with ABA in plants. Taken
      together, these results suggest that among the phytohormones tested here, JA and
      ethylene play important role(s) in regulating OsBBPI expression, with an intimate
      interaction with light signals. Finally, that the induced OsBBPI expression
      follows a kinase-signaling cascade is implied by the use of PP2A inhibitors.

PMID- 11223258
TI  - Sequence diversity of Vipera lebetina snake venom gland serine proteinase
      homologs--result of alternative-splicing or genome alteration.
AB  - Four clones encoding homologous protein(ase)s were isolated from the Vipera
      lebetina (snake) venom gland cDNA library. One of them represented DNA encoding
      factor V activating enzyme (Siigur et al., 1999), the other is homologous to
      VLFVA but has two principal discrepancies in the translated protein sequence in
      comparison with snake venom serine proteinase structures: in the active site
      triad Ser195 is replaced by Asn195 and His57 by Arg57. The third and the fourth
      clone represent combinations of the first two clones. The possibilities of
      generation of such clones via trans-splicing of the primary gene transcript, by
      exon shuffling or by unequal crossing-over on the genome level are discussed.

PMID- 11223259
TI  - Cloning and characterization of full-length human ribosomal protein L15 cDNA
      which was overexpressed in esophageal cancer.
AB  - The aim of this investigation was trying to identify the genes differentially
      expressed in esophageal cancer. By combining suppression subtractive
      hybridization (SSH) with reverse Northern high density blots, a gene named EC45
      was obtained, which dramatically overexpressed in 70% esophageal cancer (18/26).
      EC45 was mapped to 3p12-3p11.2 by radiation hybrid mapping (RH mapping). The
      putative full length EC45 cDNA (1987 bp) was identified by cDNA libraries
      screening of esophageal cancer. EC45 encoded 204 amino acids, and it shared a
      100% similarity with ribosomal protein L15 (635 bp, mRNA) in ORF, but no
      similarity in 5' UTR or 3' UTR. Northern blot panel of multiple adult human
      normal tissues showed EC45 distributed in almost normal tissues tested. All these
      data suggested that EC45, encoding ribosomal protein L15 and overexpressing in
      esophageal cancer might play a possible role in carcinogenesis of esophagus.

PMID- 11223261
TI  - New BEL-like LTR-retrotransposons in Fugu rubripes, Caenorhabditis elegans, and
      Drosophila melanogaster.
AB  - The BEL group of retroelements is present in greater numbers, variety and
      taxonomic range than may have been thought previously. In addition to the
      insects, nematodes and schistosomes, BEL-like elements are present in
      echinoderms, urochordates, and at least two highly diverged species of fish. We
      describe one new full-length BEL-like element in Fugu that we call Suzu, another
      in Drosophila that we call Tinker, and seven new families in C. elegans. Many of
      the C. elegans elements have an unusual insertion at the 5' end. The previously
      known Roo, TRAM and Telemac are also BEL-like retrotransposons. Some BEL-like
      elements have captured an envelope gene, probably from other retroelements in
      some cases but from a phlebovirus in one case.

PMID- 11223260
TI  - Discovery of new human beta-defensins using a genomics-based approach.
AB  - Epithelial beta-defensins are broad-spectrum cationic antimicrobial peptides that
      also act as chemokines for adaptive immune cells. In the human genome, all known
      defensin genes cluster to a <1 Mb region of chromosome 8p22-p23. To identify new
      defensin genes, the DNA sequence from a contig of large-insert genomic clones
      from the region containing human beta-defensin-2 (HBD-2) was analyzed for the
      presence of defensin genes. This sequence survey identified a novel beta
      defensin, termed HBD-3. The HBD-3 gene contains two exons, is located 13 kb
      upstream from the HBD-2 gene, and it is transcribed in the same direction. A
      partial HBD-3 cDNA clone was amplified from cDNA derived from IL-1beta induced
      fetal lung tissue. The cDNA sequence encodes for a 67 amino acid peptide that is
      approximately 43% identical to HBD-2 and shares the beta-defensin six cysteine
      motif. By PCR analysis of two commercial cDNA panels, HBD-3 expression was
      detected in adult heart, skeletal muscle, placenta and in fetal thymus. From RT
      PCR experiments, HBD-3 expression was observed in skin, esophagus, gingival
      keratinocytes, placenta and trachea. Furthermore, in fetal lung explants and
      gingival keratinocytes, HBD-3 mRNA expression was induced by IL-1beta. Additional
      sequence analysis identified the HE2 (human epididymis secretory protein) gene 17
      kb upstream from the HBD-3 gene. One splice variant of this gene (HE2beta1)
      encodes a beta-defensin consensus cysteine motif, suggesting it represents a
      defensin gene product. HE2beta1 mRNA expression was detected in gingival
      keratinocytes and bronchial epithelia using RT-PCR analysis. The discovery of
      these novel beta-defensin genes may allow further understanding of the role of
      defensins in host immunity at mucosal surfaces.

PMID- 11223262
TI  - Cloning of the Retinoblastoma cDNA from the Japanese medaka (Oryzias latipes) and
      preliminary evidence of mutational alterations in chemically-induced
      retinoblastomas.
AB  - We have cloned a medaka homolog of the human retinoblastoma (Rb) susceptibility
      gene. The medaka Rb cDNA encodes a predicted protein of 909 amino acids. DNA
      sequence analysis with other vertebrate Rb sequences demonstrates that the medaka
      Rb cDNA is highly conserved in regions of functional importance. An antibody
      raised against an epitope of the human pRb recognizes the protein product of the
      medaka Rb gene, detecting a 105 kDa protein in all tissues examined and at
      differential levels for the stages of embryonic development studied. The sequence
      reported herein, combined with the high degree of conservation observed in
      critical domains, has also facilitated a preliminary investigation of the
      molecular etiology of chemically-induced retinoblastoma. The mutational
      alterations characterized suggest that medaka may provide a novel model and,
      thus, provide additional insight into the human retinoblastoma condition.

PMID- 11223263
TI  - The DBP transcriptional activation domain is highly homologous to that of HLF and
      TEF and is not responsible for the tissue type-specific transcriptional activity
      of DBP.
AB  - DBP, HLF and TEF comprise a distinct subfamily of mammalian bZIP proteins that
      plays an important role in regulation of tissue-specific gene expression,
      particularly in the liver. In this report we demonstrate that DBP contains a 38
      amino acid TAD which is highly homologous to the HLF and TEF TADs that we have
      delineated previously. Deletion of this domain completely abrogates
      transcriptional activity of native DBP and GAL4-DBP fusion proteins. This domain
      functions as a modular TAD that is a potent transcriptional activator when fused
      to the GAL4 DBD. While DBP itself is a liver-specific transactivator, the DBP TAD
      is active in a variety of cell types, indicating that liver-specific activity is
      not an intrinsic property of the TAD and must be conferred by other regions of
      the protein. Using GAL4-HLF fusion proteins, we further refine the core TAD of
      PAR proteins to a region of 13 amino acids. Recently described PAR-bZIP proteins
      from Drosophila and zebrafish also contain domains that share strong homology
      with the TAD of mammalian PAR proteins, making this one of the most highly
      evolutionarily conserved TADs identified to date.

PMID- 11223264
TI  - Maque, a family of extremely short interspersed repetitive elements:
      characterization, possible mechanism of transposition, and evolutionary
      implications.
AB  - Database analysis revealed a novel family of very short interspersed repetitive
      elements named Maque in the African malaria mosquito, Anopheles gambiae. Past
      mobility of Maque was demonstrated by evidence of its insertion that resulted in
      a target duplication. Approximately 220 copies of Maque were present in the A.
      gambiae genome. Although only approximately 60 bp long, Maque has the appearance
      of a distinct transposition unit. Eleven of the 12 Maque elements found in the
      database were flanked by 9-14 bp direct repeats, indicating that their
      transposition was relatively recent. Sequence comparison and phylogenetic
      analyses suggest that there are at least two subgroups within the Maque family,
      suggesting that they may have been originated from more than one source. Five of
      the 12 Maque elements had at least one other repetitive element nearby. Three of
      the Maque elements were found near genes. However, Maque was not found in the
      coding regions of genes or in any of the expressed sequence tags (ESTs), which is
      consistent with its significantly biased distribution toward A + T rich regions.
      Several characteristics of Maque indicate that it is likely a non-autonomous
      retro-element. The evolutionary origin of Maque and the differences between Maque
      and other known retro-elements including short interspersed repetitive elements
      (SINEs) are discussed. A hypothesis is proposed in which short sequences
      containing just the reverse transcriptase recognition signal (RTRS) could
      potentially contribute to exon shuffling and the genesis of some primordial
      SINEs.

PMID- 11223265
TI  - The Streptomyces venezuelae pikAV gene contains a transcription unit essential
      for expression of enzymes involved in glycosylation of narbonolide and 10
      deoxymethynolide.
AB  - In Streptomyces venezuelae, four polyketide synthase (PKS) polypeptides encoded
      by pikAI-pikAIV are used to generate 10 and 12-membered macrocyclic structures,
      narbonolide and 10-deoxymethynolide. Sequence analysis suggests these genes are
      translationally coupled with downstream genes, pikAV (encoding a type II
      thioesterase), desVIII-desVI (encoding enzymes responsible for production of the
      final glycosylated products pikromycin, narbomycin, methymycin and neomethymycin)
      and desR (a resistance gene). Type II thioesterases have been suggested to have
      an editing function in polyketide biosynthesis and deletion of the corresponding
      genes often leads to decreased levels of polyketide production. Surprisingly an
      in-frame deletion of 687 bp of the 843 bp pikAV ORF led to a strain SC1022 that
      produced normal yields of polyketide products, but only in the aglycone form.
      Plasmid-based expression of the desVIII-VI and desR in the SC1022 strain
      completely restored production of glycosylated products, despite the absence of a
      functional pikAV gene product. Under these conditions the PikAV TEII therefore
      does not play an important role in polyketide biosynthesis, and its function
      remains an enigma. These observations also demonstrate that the region of pikAV
      DNA deleted in strain SC1022 contains a transcription unit essential for
      expression of the des genes. A sequence alignment of PikAV with members of the
      highly conserved type II thioesterases revealed a short divergent region at the
      carboxy terminus, suggesting a region of pikAV that might contain such a
      transcription unit. DNA containing this region of pikAV was shown to be able to
      increase plasmid-based expression of both crotonyl CoA reductase gene (ccr) and
      the erythromycin resistance gene (ermE) in S. venezuelae.

PMID- 11223266
TI  - Expression sequence tag-specific full-length cDNA cloning: actin cDNAs.
AB  - Current strategies for cDNA cloning are based on construction of cDNA libraries
      and colony screening. The process of obtaining a full-length cDNA clone can be
      highly time and labor intensive. Using the human actin gene as a model target
      cDNA, we have developed an RNA-capture method for rapid cloning of full-length
      cDNAs. The approach involves the capture of mRNA with expressed sequence tag
      (EST)-derived, biotin labeled antisense "capture" primers and streptavidin-coated
      magnetic beads. Full-length cDNA is then synthesized from purified EST-specific
      mRNA and cloned directly into plasmid vectors. The results of using beta-actin
      based capture primers on cytoplasmic RNA were the isolation of both beta- and
      gamma-actin cDNA clones. Of the 16 actin-specific cDNA clones analyzed, 15 (93%)
      were full-length. This approach for cloning full-length cDNAs from available ESTs
      or partial cDNA sequences will facilitate a more rapid and efficient
      characterization of gene structure and function.

PMID- 11223267
TI  - Codon bias at the 3'-side of the initiation codon is correlated with translation
      initiation efficiency in Escherichia coli.
AB  - The codon that follows the AUG initiation triplet (+2 codon) affects gene
      expression in Escherichia coli. We have extended this analysis using two model
      genes lacking any apparent Shine-Dalgarno sequence. Depending on the identity of
      the +2 codon a difference in gene expression up to 20-fold could be obtained. The
      effects did not correlate with the levels of intracellular pools of cognate tRNA
      for the +2 codon, with putative secondary mRNA structures, or with mRNA
      stability. However, most +2 iso-codons that were decoded by the same species of
      tRNA gave pairwise similar effects, suggesting that the effect on gene expression
      was associated with the decoding tRNA. High adenine content of the +2 codon was
      associated with high gene expression. Of the fourteen +2 codons that mediated the
      highest efficiency, all except two had an adenine as the first base of the codon.
      Analysis of the 3540 E. coli genes from the TransTerm database revealed that
      codons associated with high gene expression in the two expression systems are
      over-represented at the +2 position in natural genes. Codons that are associated
      with low gene expression are under-represented. The data suggest that evolution
      has favored codons at the +2 position that give high translation initiation.

PMID- 11223268
TI  - Molecular cloning of human and mouse DJ-1 genes and identification of Sp1
      dependent activation of the human DJ-1 promoter.
AB  - DJ-1 has been identified as a novel oncogene that transforms mouse NIH3T3 cells
      in cooperation with activated ras. Subsequently, two other groups have identified
      SP22 or CAP-1, rat homologs of human DJ-1, as a sperm protein targeted by some
      toxicants leading to male infertility, and another group has also reported that
      RS, the same as human DJ-1, is a component of an RNA-binding protein complex. To
      characterize the expression or functional importance of DJ-1, the genomic DNAs of
      both human and mouse DJ-1 were cloned and characterized. Both genomic DNAs
      comprise 7 exons spanning about 16-24 kb, in which 2-6 exons encode the DJ-1
      protein. The human DJ-1 gene was mapped at chromosome 1p36.2-p36.3, a region that
      has been shown to be a hot spot of chromosome abnormalities in several tumor
      cells. To analyze the promoter of the human DJ-1 gene, a series of deletion
      constructs of the region upstream of exon 2 were linked to the luciferase gene,
      and their luciferase activities were measured in human HeLa cells. Of the many
      putative transcription regulatory sequences, the Sp1 site present at -100 from
      the transcription initiation site contributed to the major promoter activity, and
      Sp1 was identified as a protein binding to this site by a mobility shift assay
      using HeLa nuclear extract.

PMID- 11223269
TI  - Parents' support of their other children after a miscarriage or perinatal death.
AB  - OBJECTIVES: This study, which grew out of the author's counselling work with the
      Edinburgh Stillbirth and Neonatal Death Society, explores the way parents who
      have recently lost a baby support other children in the family. In view of recent
      research in America on the continuing but changing bonds with the deceased, the
      place which the parents give to the deceased baby in the ongoing life of the
      family was also examined. DESIGN OF STUDY: Data were collected through semi
      structured interviews with eight families who had initially contacted the
      Edinburgh Stillbirth and Neonatal Death Society (SANDS). RESULTS: The kinds of
      support parents provided and felt was needed fell under three main headings:
      recognising and acknowledging the child's grief, including the child in family
      rituals and keeping the baby alive in the family memory. CONCLUSIONS: While there
      was some consistency in the kinds of support parents recognised as required, the
      parents own circumstances and beliefs influenced the way support was given.
      Further research might explore these factors with a larger sample. There did seem
      to be a recognition by parents, in their longer-term support and the range of
      family activities, of continuing and changing bonds with the deceased baby rather
      than the severing of bonds.

PMID- 11223270
TI  - The present status of exogenous surfactant for the newborn.
AB  - This year is the 20th anniversary of the first successful trial of exogenous
      surfactant for respiratory distress syndrome in the newborn and it is perhaps a
      good time to review recent advances in basic science and clinical practice as
      they relate to surfactant therapy.

PMID- 11223271
TI  - Congenital malformations among infants whose mothers had gestational diabetes or
      preexisting diabetes.
AB  - BACKGROUND: Diabetes type 1 is associated with an increased risk for infant
      congenital malformations. It is debated whether this is true also at gestational
      diabetes. AIMS: To study occurrence of congenital malformations in infants whose
      mothers had preexisting or gestational diabetes. STUDY DESIGN: A register study
      covering over 1.2 million Swedish births in 1987-1997 based on the Swedish health
      registries. SUBJECTS: We identified from the Medical Birth Registry 3864 infants
      born of women with preexisting diabetes and 8688 infants born of women with
      gestational diabetes. OUTCOMES MEASURES: Congenital malformations identified in
      the Medical Birth Registry, the Registry of Congenital Malformations, and the
      Hospital Discharge Registry. The rates of congenital malformations among these
      infants was compared with the population rates. RESULTS: At preexisting diabetes,
      the total malformation rate was 9.5% while the rate at gestational diabetes was
      similar to the population rate, 5.7%. At preexisting diabetes, certain conditions
      were more common than expected: orofacial clefts, cardiovascular defects,
      oesophageal/intestinal atresia, hypospadias, limb reduction defects, spine
      malformations, and polydactyly. For some of these conditions, an excess was found
      also for infants whose mothers had gestational diabetes. Infants with multiple
      malformations were in excess at preexisting diabetes but not at gestational
      diabetes but the specific type of malformations involved were similar in the two
      diabetes groups. CONCLUSIONS: It is suggested that in the group of gestational
      diabetes exists a subgroup with an increased risk for a diabetes embryopathy,
      perhaps due to preexisting but undetected diabetes type 2.

PMID- 11223272
TI  - Longitudinal follow-up of children born preterm: somatic and mental health, self
      esteem and quality of life at age 19.
AB  - In a long-term prospective study, 39 preterm children born before 35 completed
      weeks of gestation and 23 full-term children were followed up at 19 years of age.
      Information about somatic and mental health was obtained through interviews and
      confirmed by medical records. Self-esteem and quality of life were assessed from
      the subjects' perspective. Significantly more preterms than full-terms had
      somatic health problems, both during childhood and adolescence and also at age
      19. A wide spectrum of diagnoses was represented. Preterms with moderately severe
      somatic problems also showed signs of psychological distress. The frequency of
      mental health problems did not differ between the groups. Preterms and full-terms
      had similarly positive scores regarding self-esteem and quality of life.
      Altogether, the results indicate that apart from some vulnerability regarding
      physical health, this group of moderately immature subjects born preterm seems to
      function as well as young adults in general in important domains of life.

PMID- 11223273
TI  - Two types of umbilical venous pulsations and outcome of high-risk pregnancy.
AB  - Normally, blood flows evenly in the umbilical vein, without fluctuation. A
      pulsating pattern has been reported during fetal heart failure and asphyxia.
      Recently we have noticed two types of pulsating pattern; its relationship to
      adverse outcome is unclear. In a prospective multicenter study, recording of
      umbilical cord venous blood flow was conducted in high-risk pregnancies admitted
      for routine artery Doppler. In cases of pulsating flow or signs of vascular
      resistance in the umbilical artery, the examination was extended to the intra
      abdominal part of the umbilical vein. Venous pulsation, single or double, were
      noted and correlated to perinatal outcome. Venous flow pulsatility was noted in
      83 fetuses during 2 years, 26 had a double pulsating pattern, which was closely
      related to increased vascular resistance in the umbilical artery and perinatal
      mortality. A single pulsating venous pattern in one location had a good
      prognosis. In conclusion a double pulsating venous pattern, especially if
      extending to the cord, is an ominous finding in high-risk pregnancy associated
      with poor perinatal outcome. A single pulsating pattern predicted a much better
      outcome and might be an indication for delivery in the high-risk case.

PMID- 11223274
TI  - Apnoea of prematurity and arousal from sleep.
AB  - The incidence of sudden infant death syndrome (SIDS) has been found to be
      consistently higher in preterm and low birth weight infants than in infants born
      at term and this increase is inversely related to gestational age. The incidence
      and severity of apnoea of prematurity, are also inversely related to gestational
      age. The aim of this study was to investigate whether a neonatal history of
      apnoea/bradycardia affected the maturation of arousal responses. Twenty-five
      premature infants were studied. A perinatal risk score was determined for each
      infant and infants were divided into those with a neonatal history of
      apnoea/bradycardia (n=16) and those without (n=9). All infants were studied using
      daytime polysomnography on three occasions: (a) a preterm study around 36 weeks
      gestation, (b) within 3 weeks of term, and (c) 2-3 months post-term. Multiple
      measurements of arousal threshold (cm H2O) in response to air-jet stimulation
      applied alternately to the nares were made in both active sleep (AS) and quiet
      sleep (QS). Arousal thresholds were elevated in apnoeic infants compared to
      control infants in both AS (P<0.05) and QS (P<0.001) at the term study and in QS
      at 2-3 months post-term (P<0.01). In addition, arousal thresholds were positively
      correlated with perinatal risk score in both sleep states, in all studies, with
      the exception of AS at 2-3 months when all infants were readily arouseable. We
      conclude that a history of prematurity with neonatal apnoea has a persisting
      effect on decreasing arousabilty from sleep and these infants may be at increased
      risk for SIDS.

PMID- 11223275
TI  - Fetal habituation to vibroacoustic stimulation in relation to fetal states and
      fetal heart rate parameters.
AB  - OBJECTIVES: Fetal habituation to repeated stimulation has the potential to become
      a tool in the assessment of fetal condition and of the function of the fetal
      central nervous system (CNS). However, the influence of fetal quiescence and
      activity on habituation remains to be clarified. We studied habituation and the
      influence of fetal state and fetal heart rate (FHR) parameters on habituation in
      healthy term fetuses. SUBJECTS AND METHOD: We studied habituation in 37 healthy
      fetuses in two tests with an interval of 10 min. The vibroacoustic stimuli were
      applied to the maternal abdomen above the fetal legs for a period of 1 s every 30
      s. A fetal trunk movement within 1 s after stimulation was defined as a positive
      response. Habituation rate is defined as the number of stimuli applied before an
      observed non-response to four consecutive stimuli. The FHR patterns (FHRP) of the
      10 min observation period before and after the tests were visually classified.
      Fetal states were defined according to the FHRP. Baseline FHR, FHR variability
      and the number of accelerations were calculated in a subgroup of 25 fetuses.
      RESULTS: Of the 32 fetuses that responded normally during the first test, 26
      habituated and six had persistent responses. The median habituation rate
      decreased significantly in the second test (P=0.001). There was no difference in
      habituation rate between fetuses that where initially in a quiet state and those
      in an active state. The FHR parameters before the first test and the difference
      between these FHR parameters before and after the test did not correlate with the
      habituation rate. CONCLUSIONS: Although the majority of healthy fetuses was able
      to habituate, the interfetal variability in habituation performance is such that
      testing of habituation seems not to be a sensitive tool for the assessment of the
      fetal CNS. This variability is neither the result of differences in fetal state
      nor of the various FHR parameters before testing, nor of the difference in change
      of FHR parameters arising from stimulation.

PMID- 11223276
TI  - Rate influences on tone burst summating potential amplitude in
      electrocochleography: clinical(a) and experimental(b) data.
AB  - Electrocochleographic recordings of action and summating potentials are widely
      used in the electrophysiological assessment of endolymphatic hydrops (ELH).
      Increased amplitudes of the summating potential (SP) in response to tone burst
      stimuli are indicative of positive ELH. This study reports the effect of
      repetition rate of tone burst stimulation on the SP amplitude. Using
      transtympanic electrocochleography (ECochG), the SP in response to 1 kHz tone
      bursts was recorded in both a Meniere and a non-Meniere population. Absolute
      values of the SP were systematically higher in the Meniere group. Moreover, in
      the Meniere and non-Meniere groups, the response amplitudes of the SP at a
      repetition rate of 8.4 tone bursts/s were only 66 and 32%, respectively, of the
      maximal response amplitude which was obtained at the rate of 37.4 tone bursts/s.
      Additionally, in normal guinea pigs chronically implanted with a round window
      electrode, the SP was recorded to 0.5-16 kHz tone burst stimulations presented at
      100 dB SPL with the same different repetition rates. Similar enhancement of the
      SP amplitude was observed from 8.4 to 37.4 stimuli/s, whatever the frequency.
      This effect is interpreted as an increased asymmetry of vibration of the cochlear
      partition, whose mechanical operating point would not return to the normal
      resting position at high repetition rates, since it is permanently shifted in
      ELH.

PMID- 11223277
TI  - No evidence of auditory dysfunction in guinea pigs immunized with myelin P0
      protein.
AB  - Recent data have focused on the peripheral nerve myelin glycoprotein P0 as a
      putative autoantigen involved in the autoimmune etiology of some cases of
      Meniere's disease, idiopathic sensorineural hearing loss and sudden deafness. To
      determine whether antibodies to myelin P0 can alter cochlear function, 13 healthy
      guinea pigs were immunized with purified porcine myelin P0 while 10 controls were
      injected with saline water. The animals were then evaluated for evidence of
      evolving inner ear disease using immunological, electrophysiological and
      morphological methods. Twenty-six experimental ears were tested weekly with a
      brainstem auditory evoked potential technique for a period of 4 months and were
      compared to 20 control ears. Uniformly, all P0-sensitized guinea pigs showed
      antibodies to myelin protein P0 as evidenced by ELISA. Clinical signs of
      inflammatory demyelination were not discernible in P0-sensitized guinea pigs and
      all the animals were qualitatively normal. No significant increase of evoked
      potential thresholds was found in the P0-sensitized animals when compared to
      controls (P>0.05). Peak latencies of waves I, II, III, IV and V and inter-peak
      latencies in P0-sensitized guinea pigs did not significantly differ from those of
      controls (P>0.05). Histological sections of inner ear and peripheral nerves were
      free of disease in both groups. These findings indicate that the sole presence of
      antibodies to myelin P0 in the sera of guinea pigs or patients suspected of
      having autoimmune inner ear diseases is unlikely to elicit auditory abnormalities
      and that additional factors are necessary for the pathogenic development of these
      disorders.

PMID- 11223278
TI  - Effects of underwater noise on auditory sensitivity of a cyprinid fish.
AB  - The ability of a fish to interpret acoustic information in its environment is
      crucial for its survival. Thus, it is important to understand how underwater
      noise affects fish hearing. In this study, the fathead minnow (Pimephales
      promelas) was used to examine: (1) the immediate effects of white noise exposure
      (0.3-4.0 kHz, 142 dB re: 1 microPa) on auditory thresholds and (2) recovery after
      exposure. Audiograms were measured using the auditory brainstem response protocol
      and compared to baseline audiograms of fathead minnows not exposed to noise.
      Immediately after exposure to 24 h of white noise, five out of the eight
      frequencies tested showed a significantly higher threshold compared to the
      baseline fish. Recovery was found to depend on both duration of noise exposure
      and auditory frequency. These results support the hypothesis that the auditory
      threshold of the fathead minnow can be altered by white noise, especially in its
      most sensitive hearing range (0.8-2.0 kHz), and provide evidence that these
      effects can be long term (>14 days).

PMID- 11223279
TI  - The effect of proteolytic enzymes on the alpha9-nicotinic receptor-mediated
      response in isolated frog vestibular hair cells.
AB  - In frog vestibular organs, efferent neurons exclusively innervate type II hair
      cells. Acetylcholine, the predominant efferent transmitter, acting on
      acetylcholine receptors of these hair cells ultimately inhibits and/or
      facilitates vestibular afferent firing. A coupling between alpha9-nicotinic
      acetylcholine receptors (alpha9nAChR) and apamin-sensitive, small-conductance,
      calcium-dependent potassium channels (SK) is thought to drive the inhibition by
      hyperpolarizing hair cells thereby decreasing their release of transmitter onto
      afferents. The presence of alpha9nAChR in these cells was demonstrated using
      pharmacological, immunocytochemical, and molecular biological techniques.
      However, fewer than 10% of saccular hair cells dissociated using protease VIII,
      protease XXIV, or papain responded to acetylcholine during perforated-patch clamp
      recordings. When present, these responses were invariably transient, small in
      amplitude, and difficult to characterize. In contrast, the majority of saccular
      hair cells ( approximately 90%) dissociated using trypsin consistently responded
      to acetylcholine with an increase in outward current and concomitant
      hyperpolarization. In agreement with alpha9nAChR pharmacology obtained in other
      hair cells, the acetylcholine response in saccular hair cells was reversibly
      antagonized by strychnine, curare, tetraethylammonium, and apamin. Brief
      perfusions with either protease or papain permanently abolished the alpha9
      nicotinic response in isolated saccular hair cells. These enzymes when
      inactivated became completely ineffective at abolishing the alpha9-nicotinic
      response, suggesting an enzymatic interaction with the alpha9nAChR and/or
      downstream effector. The mechanism by which these enzymes render saccular hair
      cells unresponsive to acetylcholine remains unknown, but it most likely involves
      proteolysis of alpha9nAChR, SK, or both.

PMID- 11223280
TI  - A biochemical model of peripheral tinnitus.
AB  - Subjective tinnitus may be defined as the perceptual correlate of altered
      spontaneous neural activity occurring in the absence of an externally evoking
      auditory stimulus. Tinnitus can be caused or exacerbated by one or more of five
      forms of stress. We propose and provide evidence supporting a model that
      explains, but is not limited to, peripheral (cochlear) tinnitus. In this model,
      naturally occurring opioid dynorphins are released from lateral efferent axons
      into the synaptic region beneath the cochlear inner hair cells during stressful
      episodes. In the presence of dynorphins, the excitatory neurotransmitter
      glutamate, released by inner hair cells in response to stimuli or (spontaneously)
      in silence, is enhanced at cochlear N-methyl-D-aspartate (NMDA) receptors. This
      results in altered neural excitability and/or an altered discharge spectrum in
      (modiolar-oriented) type I neurons normally characterized by low rates of
      spontaneous discharge and relatively poor thresholds. It is also possible that
      chronic exposure to dynorphins leads to auditory neural excitotoxicity via the
      same receptor mechanism. Finally, the proposed excitatory interactions of
      dynorphins and glutamate at NMDA receptors need not be restricted to the auditory
      periphery.

PMID- 11223281
TI  - Cochlear implant thresholds: comparison of middle latency responses with
      psychophysical and cortical-spike-activity thresholds.
AB  - The electrically evoked middle latency response (EMLR) is a potentially useful
      measure of activation of the auditory system by a cochlear prosthesis. The
      present study compared cochlear prosthesis thresholds determined using EMLR with
      thresholds determined for psychophysical detection and for spike activity in
      cortical neurons. In systemically deafened guinea pigs, the difference between
      EMLR and psychophysical threshold level varied, with differences ranging from 
      4.6 dB (EMLR threshold more sensitive) to +10.7 dB (psychophysical threshold more
      sensitive) across animals and phase durations. Threshold differences between EMLR
      and auditory cortex neural spike responses were similar in magnitude and range (
      6 to +15 dB) to those seen for EMLR vs. psychophysical thresholds. These ranges
      are comparable to the behavioral operating range for a given condition. In 3 of
      12 subjects, the EMLR was absent for some or all electrode configurations tested,
      even at levels well above the threshold for psychophysical detection or cortical
      neuronal response. These results suggest that neither the EMLR thresholds nor
      cortical neuronal spike thresholds are an adequate substitute for psychophysical
      measures of threshold. While not sufficient for use in place of psychophysical
      measures, EMLR threshold level is strongly correlated with psychophysical
      threshold level across subjects (R(2)=0.82). Interestingly, plots of thresholds
      vs. phase duration were roughly parallel for psychophysical and EMLR thresholds,
      in contrast to the divergence of psychophysical and more peripheral (e.g.,
      electrically evoked auditory brainstem response) evoked neural threshold vs.
      phase duration functions.

PMID- 11223283
TI  - Electrically evoked otoacoustic emissions from apical and basal perilymphatic
      electrode positions in the guinea pig cochlea.
AB  - Stimulation of the cochlea with sinusoidal current results in the production of
      an otoacoustic emission at the primary frequency of the stimulus current. In this
      study we test the hypothesis that the wide frequency response from round window
      (RW) stimulation is due to the involvement of a relatively large spatial segment
      of the organ of Corti. Tonotopically organized group delays would be evident from
      perilymphatic electrode locations that restrict the spatial extent of hair cell
      stimulation. Monopolar and bipolar-paired stimulus electrodes were placed in
      perilymphatic areas of the first or third cochlear turns and the electrically
      evoked otoacoustic emissions (EEOAE) produced by these electrodes were compared
      to that from the RW monopolar electrode in the anesthetized guinea pig. Current
      stimuli of 35 microA RMS were swept across the frequency range between 60 Hz and
      100 kHz. The EEOAE was measured using a microphone coupled to the ear canal. It
      was found that the bandwidth of EEOAEs from RW stimulation extended to at least
      40 kHz and was a relatively insensitive to electrode location on the RW. The
      group delay of the EEOAE from stimulation at the RW membrane (corrected to stapes
      motion) was about 53 micros. First and third turn stimulations from electrode
      placements in perilymph near the bony wall of cochlea yielded narrower band EEOAE
      magnitude spectra but which had the same short group delays as for RW
      stimulation. A confined current (from a bipolar electrode pair) applied close to
      the basilar membrane (BM) in the first turn produced the narrowest frequency-band
      magnitude emissions and a mean corrected group delay of 176 micros for a location
      approximately 3 mm from the high frequency end of the BM (corresponding to about
      the 18 kHz best frequency location). Bipolar electrodes in the third turn scala
      tympani produced low pass EEOAE magnitude functions with corrected group delays
      ranging between approximately 0.3 and 1 ms. The average phase slopes did not
      change with altered cochlear sensitivity and postmortem. These data indicate that
      the EEOAE from RW stimulation is the summed response from a wide-tonotopic
      distribution of outer hair cells. A preliminary model study indicates that short
      time delayed emissions are the result of a large spatial distribution of current
      applied to perilymphatic locations possibly giving rise to "wave-fixed"
      emissions.

PMID- 11223282
TI  - Regional distribution of calcium currents in frog semicircular canal hair cells.
AB  - In the present work we studied the regional expression of voltage-dependent Ca
      channels in hair cells from the frog semicircular canals, employing whole-cell
      patch-clamp on isolated and in situ hair cells. Although Ca channels are thought
      to play a major role in afferent transmission, up to now no data were available
      regarding their distribution in vestibular organs. The problem appears of
      interest, especially in the light of recent results showing the presence of
      multiple Ca current components in semicircular canal hair cells. Our data suggest
      the presence, in all regions of the crista ampullaris, of two classes of cells,
      one displaying an inactivating Ca current (R1) and one lacking it. In the former
      cells, Ca current amplitude decreased from the central to the peripheral zone
      (the maximal currents being observed in the intermediate zone). Only L-type and
      R2 current components displayed regional differences in expression, whereas the
      size and properties of R1, although variable among cells, were not regionalized.
      However, in cells lacking R1, Ca current amplitudes were similar regardless of
      cell shape and location. The possible contributions of this Ca current
      distribution to afferent discharge properties are discussed.

PMID- 11223284
TI  - Computer-simulation studies on roles of potassium currents in neurotransmission
      of the auditory nerve.
AB  - Our previous work showed that action potentials (APs) fired in spiral ganglion
      (SG) neurons broaden gradually as a result of cumulative inactivation of the
      potassium current (I(K)), or with the application of a tinnitus-inducing drug
      (quinine). These results led us to speculate that AP width could affect
      neurotransmission of the auditory nerve under both normal and pathological
      conditions. This study used both experimental and theoretical approaches to test
      this hypothesis. We first measured the effect of AP broadening on Ca2+ entry into
      SG neurons. The effect of pre-synaptic AP broadening on post-synaptic responses
      was then assessed using computer-simulations. Results showed that wider
      presynaptic APs augmented responses of all types of postsynaptic glutamatergic
      receptors mainly by amplifying responses of postsynaptic receptors whose
      locations were not well aligned with the presynaptic release sites. A cumulative
      inactivation of I(K) in SG neurons significantly enhanced the responses of
      kainate receptors at all spike rates, while the augmentations for the alpha-amino
      3-hydroxy-5-methylisoxazole-4-propionic acid and N-methyl-D-aspartic acid
      receptors were most prominent below 100 spikes/s. These modeling results suggest
      that, in addition to the AP firing rate and timing, the width of APs could affect
      the neurotransmission of the auditory nerve under both normal and pathological
      conditions.

PMID- 11223285
TI  - Human middle-ear sound transfer function and cochlear input impedance.
AB  - The middle-ear pressure gain, defined as the ear canal sound pressure to cochlear
      vestibule pressure gain, GME, and the ear canal sound pressure to stapes
      footplate velocity transfer function, SVTF, simultaneously measured in 12 fresh
      human temporal bones for the 0.05 to 10 kHz frequency range are reported. The
      mean GME magnitude reached 23.5 dB at 1.2 kHz with a slope of approximately 6
      dB/octave from 0.1 to 1.2 kHz and -6 dB/octave above 1.2 kHz. From 0.1 to 0.5
      kHz, the mean GME phase angle was 51 degrees, rolling off at -78 degrees /octave
      above this frequency. The mean SVTF magnitude reached a maximum of 0.33 mm s(
      1)/Pa at 1.0 kHz with nearly the same shape in magnitude and phase angle as the
      mean GME. The ratio of GME and SVTF provide the first direct measurements of Z(c)
      in human ears. The mean Z(c) was virtually flat with a value of 21.1 acoustic
      GOmega MKS between 0.1 and 5.0 kHz. Above 5 kHz, the mean Z(c) increased to a
      maximum value of 49.9 GOmega at 6.7 kHz. The mean Z(c) angle was near 0 degrees
      from 0.5 to 5.0 kHz, decreasing below 0.5 kHz and above 5 kHz with peaks and
      valleys.

PMID- 11223286
TI  - Relating cluster and population responses to natural sounds and tonal stimuli in
      cat primary auditory cortex.
AB  - Most information about neuronal properties in primary auditory cortex (AI) has
      been gathered using simple artificial sounds such as pure tones and broad-band
      noise. These sounds are very different from the natural sounds that are processed
      by the auditory system in real world situations. In an attempt to bridge this
      gap, simple tonal stimuli and a standard set of six natural sounds were used to
      create models relating the responses of neuronal clusters in AI of barbiturate
      anesthetized cats to the two classes of stimuli. A significant correlation was
      often found between the response to the separate frequency components of the
      natural sounds and the response to the natural sound itself. At the population
      level, this correlation resulted in a rate profile that represented robustly the
      spectral profiles of the natural sounds. There was however a significant scatter
      in the responses to the natural sound around the predictions based on the
      responses to tonal stimuli. Going the other way, in order to understand better
      the non-linearities in the responses to natural sounds, responses of neuronal
      clusters were characterized using second order Volterra kernel analysis of their
      responses to natural sounds. This characterization predicted reasonably well the
      amplitude of the response to other natural sounds, but could not reproduce the
      responses to tonal stimuli. Thus, second order non-linear characterizations, at
      least those using the Volterra kernel model, do not interpolate well between
      responses to tones and to natural sounds in auditory cortex.

PMID- 11223287
TI  - Effects of contralateral acoustical stimulation on three measures of cochlear
      function in the guinea pig.
AB  - The magnitudes of suppression of the click-evoked compound action potential of
      the auditory nerve (CAP), transient click-evoked otoacoustic emissions (TEOAEs)
      and ensemble background activity of the auditory nerve (EBA), elicited by
      contralateral acoustical stimulation, were compared in awake or lightly sedated
      guinea pigs. The contralateral ear was stimulated either by continuous broad-band
      noise or by low-pass or high-pass noise (intensity 41-62 dB SPL) with cut-off
      frequencies of 2, 8 and 12 kHz. The maximal suppression of TEOAEs was achieved by
      contralateral noise containing mainly low frequencies, whereas for suppression of
      the CAP it was necessary for middle frequencies to be present in the
      contralateral noise (less than 8 kHz). In contrast to this, EBA was suppressed
      mainly by high-frequency noise (higher than 8 kHz) whereas low- and middle
      frequency noise was ineffective in suppressing EBA. Evaluation of the root mean
      square voltage of the EBA (filtered in frequency range 0.75-1.25 kHz) enabled the
      evaluation of fast and slow components of olivocochlear activation. Both fast and
      slow effects were proportionally suppressed by individual types of contralateral
      stimulation. The mechanisms of TEOAEs and CAP generation has been confirmed in
      many earlier studies, but the origin of EBA has yet to be fully elucidated. The
      obtained data support the hypothesis that a large part of EBA is formed by
      spontaneous activity of high-frequency-tuned auditory nerve fibres. Suppression
      of the EBA magnitude during contralateral stimulation may be caused either by a
      reduced spontaneous firing rate or by a decrease in possible synchronised
      neuronal firing.

PMID- 11223288
TI  - Distortion product otoacoustic emissions in human hypercholesterolemia.
AB  - Epidemiological and experimental studies suggest that hypercholesterolemia
      promotes the development of sensorineural hearing loss; however, the underlying
      cellular pathomechanism remains obscure. In the present study, 20 healthy
      subjects and 20 patients with familial hypercholesterolemia were compared with
      respect to their hearing function. None of the 40 persons reported any history of
      hearing disorder. In accordance with this subjective impression, mean hearing
      thresholds were within the normal, age-dependent ranges in both groups. In
      contrast, the single-generator distortion product otoacoustic emissions (sgDPOAE)
      were reduced at and above 4 kHz. Input-output functions of DPOAE could be
      subdivided into three groups: (i) normal, with unity slope at low intensities and
      slope less than unity (0.24+/-0.07 dB/dB at higher intensities; (ii) pathologic,
      described by a single straight line; (iii) ill-defined, with data usually
      indistinguishable from the background noise level. The ill-defined DPOAE behavior
      was only found in patients with hypercholesterolemia; namely, for 25% of patients
      at f(2)=1.5 kHz and for 50% at f(2)=4 kHz. Patients belonging to the pathologic
      and ill-defined DPOAE groups had significantly (P<0.05) higher total serum
      cholesterol and LDL-cholesterol levels compared with subjects from the normal
      DPOAE group. While hearing thresholds of patients with ill-defined growth
      functions were not statistically different from those of normal subjects, speech
      scores were significantly reduced in these cases. The data imply that nonlinear
      mechanical processes in the cochlea are compromised in hypercholesterolemic
      patients.

PMID- 11223289
TI  - Effects of changes in stimulus level on phases of distortion product otoacoustic
      emissions.
AB  - Effect of changes in stimulus levels of both lower (f(1)) and higher (f(2))
      stimulus tones on phases of 2f(1)-f(2) component of the distortion product
      otoacoustic emission (DPOAE) was examined in five normal hearing adults. The f(2)
      was fixed at 4004 Hz in all of the measurements, and the stimulus frequency ratio
      (f(2)/f(1)) was varied from 1.15 to 1.3. Change of the level of lower stimulus
      tone (L(1)) and the level of higher stimulus tone (L(2)) showed different effects
      on the DPOAE phases. The phase lags increased with increasing L(1), when
      f(2)/f(1) was above 1.22, whereas the phase gains increased with increasing L(1),
      when f(2)/f(1) was below 1.22. On the other hand, the difference in L(2)
      minimally affected DPOAE phase at most f(1)s. The previous studies about basilar
      membrane vibration revealed that phase lags increase with increasing stimulus
      level, when the stimulus frequency is below the best frequency, while phase gains
      increase with increasing stimulus level, when the stimulus frequency is above the
      best frequency, and the effect of phase change in stimulus level diminished, when
      the stimulus frequency was far above the best frequency. Based on the comparison
      between the results of the present study and the previous findings of others
      concerning basilar membrane vibration, the DPOAE generation site is assumed to be
      located at apical of the peak of the f(2) traveling wave.

PMID- 11223290
TI  - Masking by harmonic complexes in birds: behavioral thresholds and cochlear
      responses.
AB  - Thresholds for pure tones embedded in harmonic complexes were measured
      behaviorally and physiologically for three species of birds, and physiologically
      in gerbils. The harmonic maskers were generated using the Schroeder-phase
      algorithm, characterized by monotonically increasing or decreasing phase across
      frequency. Previous work has shown that these stimuli produce large differences
      in masking in humans but not budgerigars. In this study, we show that for two
      additional species of birds, the patterns of masking were similar to those shown
      for budgerigars, with masking differing only slightly for the two Schroeder-phase
      waveforms, and in the opposite direction from that demonstrated in humans.
      Amounts of masking among species corresponded qualitatively to differences in
      their critical ratios. Evoked potential measurements in birds and gerbils
      indicated responses that were consistent with the behaviorally measured
      thresholds in birds and humans. Results are interpreted in light of differences
      in frequency selectivity and cochlear temporal processing across species.

PMID- 11223291
TI  - Does xanthine oxidase contribute to the hydroxyl radical generation in ischemia
      and reperfusion of the cochlea?
AB  - We investigated the effect of a hydroxyl radical scavenger, 1,3-dimethyl-2
      thiourea (dimethylthiourea), and two xanthine oxidase inhibitors, oxypurinol and
      allopurinol, on the threshold shift of the compound action potential (CAP) after
      transient ischemia of the cochlea. Transient ischemia of 30 min duration was
      induced in albino guinea pigs via a skull base approach. The animals were treated
      with perilymphatic perfusion of dimethylthiourea, oxypurinol or allopurinol from
      10 min before the onset of ischemia to 4 h after the termination of ischemia.
      Dimethylthiourea ameliorated the CAP threshold shifts at 4 h after the onset of
      reperfusion in a dose-dependent manner. However, oxypurinol and allopurinol did
      not affect the post-ischemic cochlear dysfunction. These results imply that the
      hydroxyl radical plays an important role in generation of cochlear dysfunction
      induced by ischemia-reperfusion and that xanthine oxidase may not be the primary
      source of this radical.

PMID- 11223292
TI  - Role of nitric oxide in focal microcirculation disorder of guinea pig cochlea.
AB  - This study was designed to evaluate the role of endogenous nitric oxide (NO) in
      focal microcirculation disorder of the guinea pig cochlea. Focal microcirculation
      disorder was induced by a photochemical reaction at the lateral wall of the
      second cochlear turn. Saline or N omega-nitro-L-arginine methyl ester (L-NAME)
      was administered before the onset of photochemical reaction. Cochlear blood flow
      (CBF) was measured at the focal lesion (ischemic core), 1 mm from the lesion in
      the apical and basal direction (ischemic border zone) by using a novel non
      contact laser blood flowmeter. NO synthase activities were measured by
      radioenzymeassay. In the saline pretreatment group, CBF was significantly
      decreased to 58.8+/-4.4% of the baseline at the ischemic core 30 min after the
      onset of photochemical reaction (P<0.01), while CBF showed no significant change
      at the ischemic border zone. In the L-NAME pretreatment group, CBF was
      significantly decreased not only at the focal lesion (48.3+/-6.5%, P<0.01), but
      also at the ischemic border zone (apical, 49.3+/-2.3%, P<0.05; basal, 58.7+/
      7.1%, P<0.05, respectively). NO synthase III activity of cochlea was increased
      significantly (P<0.01) 15 min after microcirculation disorder. These findings
      suggest that formation of endogenous NO plays a key role in the maintenance of
      CBF in acute focal cochlear microcirculation disorder.

PMID- 11223293
TI  - Distortion product otoacoustic emissions in the tree frog Hyla cinerea.
AB  - The frog inner ear contains two hearing organs: the amphibian and the basilar
      papilla. The amphibian papilla is sensitive to low- and mid-frequency stimuli
      (0.1--0.5 and 0.5--1.3 kHz, respectively, in Hyla cinerea), while the basilar
      papilla is sensitive to high-frequency stimuli (2.8--3.9 kHz in H. cinerea).
      Distortion product otoacoustic emissions (DPOAE) were recorded from the ear of
      the tree frog H. cinerea. In each of six ears investigated, a cubic distortion
      product (DP) at 2f(1)--f(2) was present when the primary frequencies f(1) and
      f(2) and the DP frequency were close to either the mid- or the high-frequency
      range. At frequencies between the sensitive ranges of both papillae, no emissions
      were observed. For the basilar papilla, the dependence of DP level on the primary
      tone frequency ratio f(2)/f(1) showed a pattern characteristic of the response of
      a single nonlinear resonator. Thus, in agreement with neural data, DPOAE from the
      basilar papilla reflect the contribution of a single auditory filter to emission
      generation.

PMID- 11223294
TI  - Nitric oxide distribution and production in the guinea pig cochlea.
AB  - Production sites and distribution of nitric oxide (NO) were detected in cochlear
      lateral wall tissue, the organ of Corti and in isolated outer hair cells (OHCs)
      from the guinea pig using the fluorescent dye, 4,5-diaminofluorescein diacetate.
      Fluorescent signal, indicating the presence of NO, was found in the afferent
      nerves and their putative endings near inner hair cells (IHCs) and putative
      efferent nerve endings near OHCs, the IHCs and OHCs, the endothelial cells of
      blood vessels of the spiral ligament, the stria vascularis, and the spiral blood
      vessels of the basilar membrane. An increased NO signal was observed following
      exposure to the substrate for NO, L-arginine, while exposure to NO synthase
      inhibitors resulted in a decrease in NO signal. Observation of OHCs at the
      subcellular level revealed differentially strong fluorescent signals at the
      locations of cuticular plate, the subcuticular plate region, the infranuclear
      region, and the region adjacent to the lateral wall. The findings indicate the
      presence of NO in the cochlea and suggest that NO may play an important role in
      both regulating vascular tone and mediating neurotransmission in guinea pig
      cochlea.

PMID- 11223295
TI  - The amplitude-modulation following response in young and aged human subjects.
AB  - The amplitude-modulation following response (AMFR) is a steady-state auditory
      response which may be an objective measure of intensity discrimination. Aged
      subjects with normal hearing have poorer intensity discrimination for low
      frequency tones measured behaviorally, which would predict poorer AMFRs for low
      frequency carriers. Experiment 1 was designed to assess age-related differences
      in AMFR characteristics. Response amplitudes were not significantly different
      among the young and aged groups for either carrier frequency (520 or 4000 Hz) or
      modulation depth (0--100%). Response phase did not vary systematically among
      groups. These results suggest that the AMFR may not be directly comparable to
      behavioral measures of intensity discrimination in aged subjects with normal
      hearing. To assess the contribution of high-frequency hearing loss on the AMFR in
      aged subjects, Experiment 2 compared AMFR amplitudes in aged subjects and in
      young subjects under the condition of high-pass masking. The amplitude of the
      AMFR was reduced at 520 Hz for both aged subjects and masked young subjects
      compared to unmasked young subjects, suggesting that reduced amplitudes in aged
      subjects with high-frequency hearing loss were associated with threshold
      elevations. Furthermore, the results suggest that the base of the cochlea
      contributes to the AMFR for low carrier frequencies.

PMID- 11223296
TI  - A model of the electrically excited human cochlear neuron. I. Contribution of
      neural substructures to the generation and propagation of spikes.
AB  - Differences in neural geometry and the fact that the soma of the human cochlear
      neuron typically is not myelinated are reasons for disagreements between single
      fiber recordings in animals and the neural code evoked in cochlear implant
      patients. We introduce a compartment model of the human cochlear neuron to study
      the excitation and propagation process of action potentials. The model can be
      used to predict (i) the points of spike generation, (ii) the time difference
      between stimulation and the arrival of a spike at the proximal end of the central
      axon, (iii) the vanishing of peripherally evoked spikes at the soma region under
      specific conditions, (iv) the influence of electrode positions on spiking
      behavior, and (v) consequences of the loss of the peripheral axon. Every subunit
      of the cochlear neuron is separately modeled. Ion channel dynamics are described
      by a modified Hodgkin--Huxley model. Influence of membrane noise is taken into
      account. Additionally, the generalized activating function is introduced as a
      tool to give an envision of the origin of spikes in the peripheral and in the
      central axon without any knowledge of the gating processes in the active
      membranes. Comparing the reactions of a human and cat cochlear neuron, we find
      differences in spiking behavior, e.g. peripherally and centrally evoked spikes
      arrive with a time difference of about 400 mus in man and 200 mus in cat.

PMID- 11223297
TI  - A model of the electrically excited human cochlear neuron. II. Influence of the
      three-dimensional cochlear structure on neural excitability.
AB  - A simplified spiraled model of the human cochlea is developed from a cross
      sectional photograph. The potential distribution within this model cochlea is
      calculated with the finite element technique for an active scala tympani implant.
      The method in the companion article [Rattay et al., 2001] allows for simulation
      of the excitation process of selected elements of the cochlear nerve. The bony
      boundary has an insulating influence along every nerve fiber which shifts the
      stimulation condition from that of a homogeneous extracellular medium towards
      constant field stimulation: for a target neuron which is stimulated by a ring
      electrode positioned just below the peripheral end of the fiber the extracellular
      voltage profile is rather linear. About half of the cochlear neurons of a
      completely innervated cochlea are excited with monopolar stimulation at three
      fold threshold intensity, whereas bipolar and especially quadrupolar stimulation
      focuses the excited region even for stronger stimuli. In contrast to single fiber
      experiments with cats, the long peripheral processes in human cochlear neurons
      cause first excitation in the periphery and, consequently, neurons with lost
      dendrite need higher stimuli.

PMID- 11223298
TI  - Vesicular bodies in fish maculae are artifacts not contributing to otolith
      growth.
AB  - The presence, morphology and possible origin of vesicle-like bodies (VBs) within
      the inner ear macular otolithic membrane of developmental stages of cichlid fish
      Oreochromis mossambicus and neonate (i.e. functionally fully developed except the
      reproductive organs) swordtail fish Xiphophorus helleri were analyzed by means of
      transmission and scanning electron microscopy (TEM and SEM, respectively)
      employing various fixation procedures. Some authors believe that these VBs are
      involved in the formation of the organic phase of inner ear otoliths (or
      statoliths in birds and mammals). Decreasing the osmolarity of the fixation
      medium from a value rather close to that of native fresh water fish tissue (i.e.
      250 mOsm and 290--300 mOsm, respectively) to a value of fixatives mostly employed
      in TEM studies (ca. 190 mOsm), the amount of VBs increased and the components of
      sensory inner ear tissue increasingly dilated. Whilst a conventional prefixation
      with aldehydes followed by osmium tetroxide postfixation yielded numerous VBs,
      only few of them were observed when the tissue was fixed with aldehydes and
      osmium tetroxide simultaneously. Therefore, the results demonstrate that inner
      ear sensory epithelia are extremely sensitive to altering fixation media. On this
      background it must be concluded that VBs are fixative (i.e. glutaraldehyde)
      induced artificial structures, so-called membrane blisters. Thus, the protein
      matrix of otoliths (and possibly that of statoliths in higher vertebrates) is
      rather provided by secretion processes than by the release of vesicles.

PMID- 11223299
TI  - Efferent innervation in the goldfish saccule examined by acetylcholinesterase
      histochemistry.
AB  - In contrast to the abundance of information available regarding the anatomy and
      physiology of afferents within the goldfish saccule, the efferent system of this
      auditory endorgan has been scarcely studied morphologically. In this study,
      acetylcholinesterase histochemistry with diaminobenzidine enhancement was used to
      describe the morphology of efferents. Under light microscopy, labeled fibers
      appeared in the distal portion of the saccular nerve, penetrated the basement
      membrane and formed a horizontal mesh-like plexus near the base of hair cells.
      Many vertical branchlets with terminal swellings protruded upward toward hair
      cells from the plexus. Under electron microscopy, dense extracellular labeling
      was present around efferent terminals, which often formed clusters on hair cells.
      Labeling was also present around unmyelinated fibers of passage within the
      sensory epithelium and the distal saccular nerve. These fibers contained coarse
      microtubules and small vesicles, and often ran in a bundle with other similar
      fibers. Based on their position within the epithelium, histochemistry and
      ultrastructural characteristics, these fibers were concluded to be efferents.
      These fibers became myelinated and unlabeled in the proximal saccular nerve.
      These results suggest that acetylcholinesterase can be a marker of entire distal
      unmyelinated portions of efferent fibers and demonstrated abundant efferent
      innervation in the goldfish saccule.

PMID- 11223300
TI  - Expression of osteopontin by exudate macrophages in inflammatory tissues of the
      middle ear: a possible association with development of tympanosclerosis.
AB  - Tympanosclerosis is a condition leading to a calcification process in the middle
      ear, and often develops after chronic inflammation of the middle ear. Since
      osteopontin (OPN) has been shown to participate in the pathological
      calcification, we here investigated whether OPN is involved in the process of
      calcification in tympanosclerosis. The tympanic membrane and middle ear mucosa,
      obtained from patients of tympanosclerosis and chronic otitis media, were
      histologically classified depending on the calcification degree. In hyalinized
      tissues with macroscopic calcification and fibrous tissues with microscopic
      calcification, OPN was immunohistochemically found in the calcification sites. In
      inflammatory tissues with microscopic calcification, OPN was also found in the
      calcifying foci, and many OPN mRNA-expressing cells, determined by in situ
      hybridization, located around their foci. Moreover, immunohistochemical double
      staining of OPN and CD68 showed that the OPN-expressing cells were CD68-positive,
      indicating these cells were macrophages. In inflammatory tissues without
      calcification, immunohistochemistry of CD68 and in situ hybridization of OPN mRNA
      revealed that most OPN mRNA-expressing cells were CD68-positive. The expression
      of OPN mRNA in inflammatory tissues was also shown by reverse transcriptase
      polymerase chain reaction. These results suggest that OPN secreted by exudate
      macrophages might be an important regulator in the calcification of
      tympanosclerosis.

PMID- 11223301
TI  - Auditory stream segregation processes operate similarly in school-aged children
      and adults.
AB  - Our previous research with adults suggests that pre-attentive (bottom-up) brain
      processes govern auditory stream segregation [Sussman et al., 1998. Brain Res.
      789, 130--138; Sussman et al., 1999. Psychophysiology 36, 22--34; Winkler et al.,
      submitted for publication]. We investigated whether the pre-attentive mechanisms
      underlying auditory stream segregation operate similarly in school-aged (7--10
      years of age) children and adults. We used an electrophysiological index of
      auditory change detection that does not require the experimental participant to
      focus on the sounds to be evoked. In Experiment 1, children were presented with
      mixtures of high and low frequency tones in different conditions and were
      instructed to watch a silent video and ignore the sounds. In Experiment 2,
      children were asked to listen to the same sets of sounds as presented in
      Experiment 1 and tell whether they heard one or two auditory streams. The pre
      attentive processing of the mixture of sounds as one or two auditory streams
      (Experiment 1), matched with the perception of the sounds as one or two distinct
      streams (Experiment 2). Our results demonstrate that the mechanisms for auditory
      stream segregation operate similarly in school-aged children and adults when
      frequency proximity is the cue for segregation.

PMID- 11223302
TI  - Electrophysiological measures of auditory function in the neurofilament-deficient
      mutant quail (Quv).
AB  - Auditory pathway electrophysiological studies were performed on the mutant quail
      'Quv'. This mutation is known to result in neurofilament deficiencies of both the
      peripheral and central nervous systems. Auditory evoked brainstem responses
      (ABRs), electrocochleograms (EcochGs) and middle latency responses (MLRs) were
      evaluated. ABRs in Quv quails demonstrated markedly altered waveforms exhibiting
      longer latencies, absence of the later peaks and lower amplitudes. The EcochG
      showed normal cochlear microphonics with no obvious abnormalities in amplitude or
      latency and normal latencies for peak N1. Quv quails had a mild threshold
      elevation with a normal latency for the first peak of the ABR (P1). The Quv MLRs
      showed no significant differences in amplitude but they revealed a latency
      prolongation for peaks N0, Pa and Na relative to the controls. We have discovered
      abnormal findings of auditory evoked potentials in the neurofilament-deficient
      quail (Quv). We suggest that the smaller axonal size and axonal hypotrophy due to
      altered neurofilament expression underlies these abnormal auditory evoked
      potential responses.

PMID- 11223303
TI  - Temporal envelope expansion of speech in noise for normal-hearing and hearing
      impaired listeners: effects on identification performance and response times.
AB  - The effects of expanding the temporal envelope of speech sounds on speech
      identification in noise were investigated in normal-hearing and hearing-impaired
      listeners. Expansion was performed by applying a power-law transformation to the
      low-frequency temporal modulations (<500 Hz) of vowel-consonant-vowel logatomes
      presented against a background noise. Stimuli were spectrally degraded, allowing
      a direct examination of the perceptual effects induced by the modification of the
      temporal envelope alone on speech reception. This study extended a previous study
      conducted by Lorenzi et al. [1999. Hear. Res. 136, 131--138] by measuring the
      effects of envelope expansion on both identification performance and response
      times in normal-hearing and hearing-impaired listeners. Overall, the results show
      that temporal expansion yields only small improvements in identification scores
      (approximately 5%) in normal-hearing listeners. No effect of expansion on
      identification scores was observed in hearing-impaired listeners. On the other
      hand, the results show that expansion led to a significant decrease in response
      times in both normal-hearing and hearing-impaired listeners. The average benefit
      from expansion was about 65 ms in both groups. These results suggest that
      expanding the temporal envelope of speech sounds presented in noise may improve
      'ease of listening' in both normal-hearing and hearing-impaired listeners.

PMID- 11223304
TI  - KCNQ1/KCNE1 potassium channels in mammalian vestibular dark cells.
AB  - The high [K(+)] in the inner ear endolymph is essential for mechanosensory
      transduction in hearing and balance. Several ion channels, including a slowly
      activating, voltage-dependent, outwardly conducting K(+) channel composed of the
      KCNQ1 (KvLQT1) and KCNE1 (IsK/minK) subunits, are expressed at the apical surface
      of vestibular dark cells. We investigated the underlying molecular mechanisms of
      this conductance using in situ hybridization, RT-PCR, and immunocytochemistry and
      by tracking the ultrastructural changes of vestibular structures in kcne1(-/-)
      mice. In the wild type mice, the KCNE1 and KCNQ1 proteins are expressed
      specifically at the apical membrane of dark cells, as early as gestational day
      (GD) 17 for KCNE1 while KCNQ1 mRNAs can be detected at GD 18. This is the first
      demonstration that the two protein components of this potassium channel co
      localize in a polarized fashion at the cellular level. Although the vestibular
      end-organs are normal at birth in kcne1(-/-) mice, they begin to show
      modifications during postnatal development: we observed an increase in the height
      of the dark cells, in their number of mitochondria, and in basolateral membrane
      infoldings. Subsequently, the epithelium degenerates and the endolymphatic space
      collapses. Similar changes are known to occur in the cardio-auditory Jervell-
      Lange-Nielsen syndrome which is caused by mutations in the same channel.

PMID- 11223305
TI  - Effects of middle-ear static pressure on pars tensa and pars flaccida of gerbil
      ears.
AB  - It has long been known that static pressure affects middle-ear function and
      conventional tympanometry uses variations in static pressure for clinical
      assessment of the middle ear. However, conventional tympanometry treats the
      entire tympanic membrane as a uniform interface between the external and middle
      ear and does not differentiate the behavior of the two components of the tympanic
      membrane, pars tensa and pars flaccida. To analyze separately the different
      acoustic behavior of these two tympanic membrane components, laser Doppler
      velocimetry is used to determine the motion of each of these two structures. The
      velocities of points near the center of p. tensa and p. flaccida in response to
      the external-ear sound pressure at different middle-ear static pressures were
      measured in nine gerbil ears. The effect of middle-ear static pressure on the
      acoustic response of both structures is similar in that non-zero middle-ear
      static pressures generally reduce the velocity magnitude of the two membrane
      components in response to sound stimuli. Middle-ear under-pressures tend to
      reduce the velocity magnitude more than do middle-ear over-pressures. The
      acoustic stiffness and inertance of both p. tensa and p. flaccida are altered by
      static pressure, as shown in our results as changes of transfer-function phase
      angle. Compared to p. tensa, p. flaccida showed larger reductions in the velocity
      magnitude to small over- and under-pressures near the ambient middle-ear
      pressure. This higher pressure sensitivity of p. flaccida has been found in all
      ears and may link the previously proposed middle-ear pressure regulating and the
      acoustic shunting functions of p. flaccida. We also describe, in both p. tensa
      and p. flaccida, a frequency dependence of the velocity measurements, hysteresis
      of velocity magnitude between different directions of pressure sweep and
      asymmetrical effects of over- and under-pressure on the point velocity.

PMID- 11223306
TI  - Quantitative analysis of rat inner ear blood flow using the iodo[(14)C]antipyrine
      technique.
AB  - A number of different qualitative and quantitative techniques have been used to
      measure inner ear blood flow and all have required that the animal be
      anesthetized. It is well known that anesthesia can cause a variety of circulatory
      as well as other systemic changes. In this study, we have employed a technique
      commonly used for quantifying brain blood flow, the iodo[(14)C]antipyrine
      technique ([(14)C]IAP). Unlike other techniques, [(14)C]IAP can be used in
      unanesthetized animals under conditions that are nearly normal, it is non
      invasive, it can be used reliably in regions of low local blood flow, and data
      can be acquired from both the periphery and central nervous system. Results show
      that blood flow to the lateral wall of the basal turn of the cochlea (387 +/- 19
      microl/g/min) is significantly higher (P<0.001) than that of the utricular macula
      (189 +/- 23 microl/g/min), horizontal (186 +/- 22 microl/g/min), superior (185 +/
      22 microl/g/min), or posterior canal crista (185 +/- 25 microl/g/min).
      Surprisingly, blood flow to all of the vestibular end-organs is remarkably
      similar. The use of this technique should allow pharmacological experimentation
      on inner ear blood flow without the unknown complications of anesthesia or
      invasive procedures.

PMID- 11223307
TI  - Responses of young and aged rat inferior colliculus neurons to sinusoidally
      amplitude modulated stimuli.
AB  - The inferior colliculus (IC) is a processing center for monaural and binaural
      auditory signals. Many units in the central nucleus of the inferior colliculus
      (CIC) respond to amplitude and frequency modulated tones, features found in
      communication signals. The present study examined potential effects of age on
      responses to sinusoidally amplitude modulated (SAM) tones in CIC and external
      cortex of the inferior colliculus (ECIC) units in young and aged F344 rats.
      Extracellular recordings from 154 localized single units of aged (24 month) rats
      were compared to recordings from 135 IC units from young adult (3 month) animals.
      SAM tones were presented at 30 dB above threshold. Comparisons were made between
      CIC and ECIC regarding the percentage of units responding to SAM stimuli, the
      relationship between SAM responsiveness and temporal response patterns, maximum
      discharge rates and maximum modulation gains, shapes of rate transfer functions
      and synchronization modulation transfer functions (MTFs) in response to SAM
      tones. Sixty percent of units in young and aged rat IC were selectively
      responsive to SAM stimuli. Eighty-one percent of units classified as onset
      temporal response patterns were not tonically responsive to SAM stimuli. Median
      maximum discharge rate in response to SAM tones was 17.6/s in young F344 rats;
      median maximum modulation gain was 3.85 dB. These measurements did not change
      significantly with age. Thirty-seven percent of young rat units displayed
      bandpass MTFs and 53% had lowpass MTFs. There was a significant age-related shift
      in the distribution of MTF shapes in both the CIC and ECIC. Aged animals showed a
      lower percentage of bandpass functions and a higher percentage of lowpass
      functions. Age-related changes observed in SAM coding may reflect an altered
      balance between excitatory/inhibitory neurotransmitter efficacy in the aged rat
      IC, and/or possibly a change in the functional dynamic range of IC neurons.

PMID- 11223308
TI  - Hair cell regeneration and recovery of auditory thresholds following
      aminoglycoside ototoxicity in Bengalese finches.
AB  - Birds regenerate auditory hair cells when original hair cells are lost.
      Regenerated hair cells become innervated and restore hearing function. Functional
      recovery during hair cell regeneration is particularly interesting in animals
      that depend on hearing for vocal communication. Bengalese finches are songbirds
      that depend on auditory feedback for normal song learning and maintenance. We
      examined the structural and functional recovery of the Bengalese finch basilar
      papilla after aminoglycoside ototoxicity. Birds were treated with the ototoxic
      aminoglycoside, amikacin, daily for 1 week. Treatment resulted in hair cell loss
      across the basal half of the basilar papilla and corresponding high frequency
      hearing loss. Hair cell regeneration and recovery of auditory brainstem responses
      were compared in the same animals. Survival times following treatment were
      between 1 day and 12 weeks. Analysis of structural recovery at weekly intervals
      indicated that hair cells in the Bengalese finch papilla require a maximum of 1
      week to regenerate and appear with immature morphology at the epithelial surface.
      An additional 6 days are required for adult-like morphology to develop.
      Repopulation of the damaged region was complete by 8 weeks. Recovery of auditory
      thresholds began 1 week after treatment and reached asymptote by 4 weeks. Slight
      residual threshold shifts at 2.0 kHz and above were observed up to 12 weeks after
      treatment. Direct comparison of structural and functional recovery indicates that
      auditory thresholds recover maximally before a full complement of hair cells has
      regenerated.

PMID- 11223309
TI  - Impact of the Edmonton Labeled Visual Information System on physician recall of
      metastatic cancer patient histories. a randomized controlled trial.
AB  - The Edmonton Labeled Visual Information System (ELVIS) is a novel method of
      documenting clinical information because it is a pictorial method of representing
      cancer burden and treatment. This randomized, crossover, multiperiod trial
      involved 16 physicians who each reviewed two ELVIS and two control (text) cancer
      patient cases (total 32 ELVIS and 32 text cases). Short-answer questionnaires
      were administered immediately and 18--24 hours following. Mean (+/- SD) recall of
      basic disease and treatment information was superior immediately following the
      ELVIS cases (83% +/- 14%) versus text cases (60% +/- 14%, P < 0.0001) and 18--24
      hours later (ELVIS cases 65% +/- 21% versus text cases 43% +/- 21%, P < 0.0001).
      Mean (+/- SD) time required to memorize information was reduced in the ELVIS
      cases (4 +/- 2 min) versus text cases (13 +/- 6 min, P < 0.0001). Ratings of
      overall physician preference strongly favored the ELVIS over text. The data
      indicate that ELVIS aids the process of learning complex cancer patient
      histories.

PMID- 11223310
TI  - Care of the dying: setting standards for symptom control in the last 48 hours of
      life.
AB  - The hospice model of care of the dying patient is regarded as a model of
      excellence; however, outcomes of this care have been poorly demonstrated.
      Integrated Care Pathways (ICPs) provide a method of recording and measuring
      outcomes of care. The ICP document replaces all previous documentation and is a
      multiprofessional record of patient care. The aim of this study was to implement
      an ICP in an inpatient hospice setting in order to set standards of care for
      symptom control in the dying phase of a patient's life. ICPs were analyzed from
      168 inpatients who died over a one-year period. Symptoms of pain, agitation, and
      respiratory tract secretions (RTS) were monitored every four hours by nursing
      staff as either present or absent. For each symptom, 80% of patients had one
      episode or complete control of the symptom, 10% had two episodes, and 10% had
      three episodes or more recorded. As death neared, there was a statistically
      significant increase in the number of patients whose pain was controlled. The ICP
      has provided a means to measure symptom control in the dying patient and set
      standards of care, which is integrated into clinical practice.

PMID- 11223311
TI  - Congruity of cancer pain perceptions between Taiwanese patients and family
      caregivers: relationship to patients' concerns about reporting pain and using
      analgesics.
AB  - The purposes of this study were twofold: first, to examine the congruity of
      cancer pain perceptions between Taiwanese cancer patients and their family
      caregivers and second, to determine if there was a relationship between this
      congruity of perception and patients' concerns about reporting pain and using
      analgesics. A total of 89 dyads of oncology inpatients and their primary family
      caregivers participated in this study. The instruments completed by patients
      consisted of Barriers Questionnaire Taiwan Form, the Brief Pain Inventory Chinese
      version (BPI), the Eastern Cooperative Oncology Group (ECOG) performance status
      scale, and a demographic questionnaire. Family caregivers completed the Brief
      Pain Inventory short form and a demographic questionnaire. The Pearson's
      correlation, intraclass correlation coefficients, and the kappa statistics
      between family caregivers and patients' pain ratings were statistically
      significant. Patients in the noncongruent group (difference of >1 on "pain now"
      scale of the BPI) experienced higher levels of pain and poor levels of
      performance status. Family caregivers in the noncongruent group were more likely
      to be older and less educated. A patient's greater concerns about reporting pain
      and using analgesics were related to a lower level of congruity concerning pain
      perception between them and their family caregivers. Interventions aimed at
      overcoming patients' concerns about reporting pain and using analgesics may have
      beneficial effects on the congruency between pain perceptions of patients and
      family caregivers.

PMID- 11223312
TI  - Assessing patient satisfaction with pain management through a continuous quality
      improvement effort.
AB  - A quasi-experimental study was conducted to evaluate patient satisfaction with
      pain management before and after a continuous quality improvement (CQI) project
      in a large, university medical center. The CQI project aim was to implement
      American Pain Society (APS) quality improvement guidelines regarding the
      recognition and prompt treatment of pain. A modified version of the questionnaire
      recommended by the APS Subcommittee on Quality Assurance Standards was used to
      survey 83 patients prior to implementation of the CQI effort and 89 patients one
      year later. Half of the patients reported moderate to severe pain both before and
      after the CQI project. Less than half reported complete relief of pain after
      treatment. Despite significant levels of pain and ineffective treatment, greater
      than 90% of patients reported being satisfied with pain management. Responses to
      open-ended questions were analyzed. Findings from the study are being used to
      develop a medical center-wide action plan to guide further CQI efforts to improve
      pain management.

PMID- 11223313
TI  - The use of highly active antiretroviral therapy (HAART) in patients with advanced
      HIV infection: impact on medical, palliative care, and quality of life outcomes.
AB  - The effect of highly active antiretroviral therapy (HAART) in the treatment of
      HIV infection is usually measured by survival, CD4 lymphocyte counts, HIV-1 RNA
      viral load testing, and the occurrence of opportunistic infections. This pilot
      study sought to measure the impact of HAART treatments on a wide range of
      clinical outcomes and psychological variables in a sample of patients with
      advanced HIV infection. Seventy patients with advanced AIDS who were protease
      inhibitor naive were started on HAART regimens. Patients were admitted to an AIDS
      inpatient unit of a long-term care facility that provides treatment and
      palliative care. All patients were diagnosed with AIDS, had CD4 cell counts below
      300/cc(3), and had a projected survival of greater than one month. Patients were
      started on triple-drug HAART regimens with daily medical supervision and
      observation. In addition to standard clinical and laboratory markers, a series of
      observer-rated and self-report instruments were used to measure various physical
      and psychological factors (e.g., pain and symptom distress, psychological well
      being, depression). Data were collected at baseline and after 1 and 3 months of
      HAART therapy. As expected, the CD4 count increased and viral load levels
      decreased significantly over the 3-month study period. In addition, patients
      improved significantly in body weight, and serum albumin and ferritin levels. The
      only psychosocial measure that improved significantly with treatment was
      depression. Ratings of pain intensity, physical and psychological symptom
      distress, and overall quality of life did not change. Of the 70 patients studied,
      84.3% were still alive after the 3-month study period. Of these, 6 (8.6%) were
      discharged to community. However, 17 surviving patients (24.3%) had HAART
      regimens discontinued due to drug intolerance and 11 patients (15.7%) expired
      during the study period. While these data are preliminary, HAART regimens appear
      to have positive effects on CD4 count, HIV viral load, and several other measures
      of physical well-being in patients with advanced AIDS. Despite these
      improvements, the benefits of treatment on pain and symptom distress, and
      psychological well-being were less clear. In addition, treatment failure
      (mortality and intolerance) were not uncommon in this sample (40%). Further
      research is clearly necessary to better understand the benefits of HAART therapy
      in patients with advanced HIV infection.

PMID- 11223314
TI  - Using a trade-show format to educate the public about death and survey public
      knowledge and needs about issues surrounding death and dying.
AB  - A public education event on death and dying, based on the design of a commercial
      trade show, was held to raise the profile of palliative care in the community.
      Attendees answered a questionnaire designed to assess their knowledge on issues
      about dying and their anticipated needs if they were to face a terminal illness.
      Healthcare providers knew significantly more about dying, but there were
      persistent misconceptions that morphine shortens life, causes addiction, and
      develops tolerance. The questionnaire revealed confusion about treatment choices
      available to patients and euthanasia. The anticipated needs questions revealed
      that increasing age leads to less concern about physical needs, and
      independence/control. Further public forums on death and dying will be held with
      attention to education on the identified issues and inclusion of wider education
      and cultural groups.

PMID- 11223315
TI  - Assessing delirium in cancer patients: the Italian versions of the Delirium
      Rating Scale and the Memorial Delirium Assessment Scale.
AB  - To validate the Italian versions of the Delirium Rating Scale (DRS) and the
      Memorial Delirium Assessment Scale (MDAS), 105 cancer patients consecutively
      referred for neurological or psychiatric consultation for mental status change
      were evaluated using the Confusion Assessment Method (CAM), the DRS, the MDAS,
      and the Mini-Mental State Examination (MMSE). According to the CAM criteria and
      clinical examination, 66 patients were delirious, and 39 received diagnoses other
      than delirium. The DRS and the MDAS scores significantly distinguished delirious
      from non-delirious patients. The MDAS and the DRS were mutually correlated. When
      using the proposed cut-off scores for the two scales, the MDAS had higher
      specificity (94%) but lower sensitivity (68%) than the DRS (sensitivity = 95%,
      specificity = 61% for DRS cut-off 10; sensitivity = 80%, specificity = 76%, DRS
      cut-off 12). The MMSE showed high sensitivity (96%) and very low specificity
      (38%). Exploratory factor analysis of the DRS and the MDAS suggested a three
      factor and two-factor structure, respectively. Both instruments in their Italian
      version proved to be useful for the assessment of delirium among cancer patients.
      Further research is needed to examine the use of the DRS and the MDAS in other
      clinical contexts.

PMID- 11223316
TI  - Transdermal fentanyl for chronic pain in AIDS: a pilot study.
AB  - This prospective, open-label, before-after trial was designed to compare the
      efficacy of oral opioids with that of transdermal fentanyl in severe AIDS-related
      chronic pain, as well as assess barriers, patient satisfaction, and side effects.
      Thirty-five sequentially selected male and female outpatients with AIDS who were
      at least 18 years old were enrolled. All had chronic pain requiring continuous
      treatment with > or = 45 mg/day oral morphine or an equivalent. Eighteen of the
      patients had a history of chemical dependency. Baseline data were collected while
      patients received their previously prescribed opioid; assessments were made again
      after a stable transdermal fentanyl dose (25--300 microg/h) had been maintained
      for 15 days. Patients completed the International Association for the Study of
      Pain Classification of Chronic Pain Syndromes questionnaire, the Brief Pain
      Inventory, and a Satisfaction With Pain Medication questionnaire for assessing
      pain intensity, relief, and interference with normal functioning. With
      transdermal fentanyl, pain severity scores decreased significantly, mean pain
      relief scores increased, and daily functioning measures improved significantly.
      Most adverse events were mild and unrelated to fentanyl use. Transdermal fentanyl
      was effective for chronic pain in both chemically dependent and non-chemically
      dependent patients with AIDS.

PMID- 11223317
TI  - Gabapentin in phantom limb pain management in children and young adults: report
      of seven cases.
AB  - Seven children and young adults with phantom limb pain (PLP) were treated with
      gabapentin. PLP resolved in six patients within two months. One patient still had
      symptoms to a lesser degree. Mean follow up time was 1.74 years. Gabapentin may
      be a useful adjunct to pain management in patients with PLP symptoms.

PMID- 11223318
TI  - Are randomized clinical trials good for us (in the short term)? Evidence for a
      "trial effect".
AB  - OBJECTIVE: To assess whether there is evidence that randomized controlled trials
      are systematically beneficial, or harmful, for patients. In other words, is there
      a "trial effect"? If so, to examine whether the evidence sheds light on the
      likely sources of the difference in outcomes. METHODS: Systematic review of the
      literature. RESULTS: We set out in some detail potential sources of a "trial
      effect" and potential biases. We found only 14 research articles (covering more
      than 21 trials) with relevant primary data. We extracted, with difficulty,
      quantitative data-sets from the articles, and classified these according to
      likely source of any apparent trial effect. The categories used were: differences
      in prognosis; superior treatment in the trial; and "protocol/Hawthorne effect"
      (benefit from improved routine care within a trial). ANALYSIS: The evidence
      available is limited in breadth (coming largely from cancer trials) and quality,
      as well as quantity. There is weak evidence to suggest that clinical trials have
      a positive effect on the outcome of participants. This does not appear to depend
      strongly on the trial demonstrating that an experimental treatment is superior.
      However, benefit to participants is less evident where scope for a
      "protocol/Hawthorne effect" was apparently limited (because there was no
      effective routine treatment or because the comparison group also received
      protocol care). A form of bias, arising if clinicians who tend to recruit to
      trials also tend to be better clinicians, could also explain these results.
      CONCLUSION: While the evidence is not conclusive, it is more likely that clinical
      trials have a positive rather than a negative effect on the outcome of patients.
      In the limited data available, the effect seems to be larger in trials where an
      effective treatment already exists and is included in the trial protocol.
      RECOMMENDATION: That carefully researched treatment protocols, and monitoring of
      outcomes, be used for all patients, not just those in trials.

PMID- 11223319
TI  - Changing rates of cancer. The hazards of using a single definition.
AB  - Changing cancer rates, abstracted from tumor registries, are used to make
      inferences about the effect of carcinogens and cancer treatments on a population
      wide basis. We compared the annual age-standardized incidence rates of extremity
      soft tissue sarcomas from two large tumor registries using different case
      definitions. We identified all limb soft tissue sarcoma cases diagnosed 1973-1993
      in the Ontario Cancer Registry (OCR) and the Surveillance, Epidemiology, and End
      Results (SEER) databases. Two case definitions for limb soft tissue sarcoma were
      used based on missing data, incomplete diagnostic methods and ICD-9 codes; an
      upper limit estimate of the rates which included all possible cases of limb soft
      tissue sarcoma and a lower limit estimate of the rates which included all
      definite cases of limb soft tissue sarcoma (with the true rates lying in
      between). The upper limit OCR rates showed a statistically significant decreasing
      linear trend (slope = -0.021, P < 0.01). Whereas the slope of the OCR lower limit
      regression line showed a statistically significant increase in rates (slope =
      0.01, P = 0.04). Neither the upper or lower limit SEER rates had a statistically
      significant linear trend (slope = 0.002, P = 0.60 and slope = 0.001, P = 0.18,
      respectively). Case definition affects incidence rates and changing rates of
      cancer. Thus the use of a single case definition along with changing coding
      practices may alone explain changing cancer rates.

PMID- 11223320
TI  - Factors associated with errors in death certificate completion. A national study
      in Taiwan.
AB  - To identify characteristics of certifying physicians and the deceased that are
      associated with errors in death certificate completion in Taiwan, we
      retrospectively reviewed 4123 systematically sampled death certificates issued in
      1994. Multivariate analyses were used to assess the associations of various
      characteristics of the certifying physicians and the deceased with four types of
      error. Of the 4123 death certificates reviewed, 2525 (61%) were completed
      correctly. In 289 (7%), only the mechanism(s) of death was given (Major Error 1);
      in 146 (4%), multiple causal sequences were given in part I (Major Error 2); in
      800 (19%), a single causal sequence was given but was not specific enough (Minor
      Error 1); and in 363 (9%), a single causal sequence was given but the order was
      incorrect (Minor Error 2). Multiple logistic regression analyses revealed that
      the probability of error in death certification increased as the age of the
      deceased increased, the age of the certifier decreased, and the level of the
      hospital decreased. These findings suggest that training in death certificate
      completion should focus on younger certifiers and those working at lower level
      teaching hospitals and nonteaching hospitals. Given the high rate of Minor Error
      1, physicians should be reminded to state information as specifically as possible
      to render cause-of-death statistics more informative.

PMID- 11223321
TI  - Recording of diabetes on death certificates. Has it improved?
AB  - OBJECTIVE: To determine whether the recording of diabetes on death certificates
      improved from 1986 to 1993. METHOD: Comparison of two National Mortality Follow
      back Surveys that selected independent samples of death certificates with the
      purpose of obtaining information from informants about the decedents. RESULTS:
      The recording of diabetes on death certificates did not improve from 1986 to
      1993. CONCLUSION: Periodic monitoring of the accuracy of death certificates is
      essential for proper interpretation of mortality statistics which are routinely
      used to describe the burden of diabetes in our society.

PMID- 11223322
TI  - Predictive modeling and heterogeneity of baseline risk in meta-analysis of
      individual patient data.
AB  - We developed and evaluated methods for the analysis and interpretation of the
      baseline risk heterogeneity in meta-analysis of individual patient data (MIPD)
      based on information on predictive factors. We used data from a typical MIPD of
      eight clinical trials (1792 patients, 2947 years of follow-up) on the efficacy of
      high-dose acyclovir in human immunodeficiency virus infection. Cox models with
      four predictive factors (age, disease state, CD4 cell count and hemoglobin
      levels) were used to estimate predicted individual hazards both for single trials
      and for various MIPD modeling methods (simple pooling, adjusted for study,
      stratified per study, fixed and random effects for predictors). For each study
      and for each method of MIPD synthesis, we estimated the odds ratio for death in
      the upper versus the lower quartile of predicted risk (Extreme Quartile Odds
      Ratio, EQuOR) and the respective rate ratio (Extreme Quartile Rate Ratio, EQuRR).
      Only the CD4 cell count showed a significantly heterogeneous predictive effect
      across the eight studies (P =.024). The EQuOR of single studies ranged from 3.5
      (little heterogeneity) to 24 (intermediate heterogeneity), substantially lower
      than the EQuOR of the MIPD (167 to 275, depending on the model used). The EQuRR
      values ranged from 3.5 to 77 for single studies and from 77 to 116 for the
      various MIPD models. Predictive modeling can be a major strength of MIPD, when
      performed and interpreted with standardized approaches. All models consistently
      show that MIPD may be a study design with extreme heterogeneity of patient
      baseline risk.

PMID- 11223323
TI  - When should an effective treatment be used? Derivation of the threshold number
      needed to treat and the minimum event rate for treatment.
AB  - Clinicians and patients must decide when treatment effects are large enough to
      more than offset the adverse effects and costs of therapy. Calculation of the
      number of patients one needs to treat (NNT) in order to prevent one patient from
      having the target event is one tool to help with this decision. Clinicians should
      treat patients when the NNT is lower than a threshold NNT at which point the
      therapeutic risk equals the therapeutic benefit. We aimed: (1) to identify the
      determinants of the threshold NNT, and (2) to derive equations for the explicit
      estimation of the threshold NNT and of the minimum expected rate of target event,
      without treatment, above which treatment is justified. We conceived the threshold
      number needed to treat to prevent one target event as the point at which the
      benefits of treating that number of patients equal the negative consequences of
      treating that same number of patients. After identifying the various elements
      comprising the treatment impact, we equated the benefits and negative
      consequences and solved the equation for threshold NNT. We then derived the
      minimum expected rate of target event which would justify treatment. We derived
      an equation that relates the threshold NNT to the treatment-attributable adverse
      event rates (AER) and the relative values (RV) of the adverse events compared to
      that of the target event prevented. Specifically, the threshold NNT, denoted
      NNT(T) is given by NNT(T) = 1/(AER(1).RV(1) +...+ AER(n).RV(n)). We also derived
      a more complex equation which addresses the costs incurred by treatment and costs
      avoided by preventing target events. Solving the equation that includes costs
      requires specifying both the value of preventing a target event and the values of
      adverse treatment effects in economic units. The threshold NNT and the relative
      risk reduction (RRR) for the target event determine the minimum target event rate
      above which treatment is justified. This minimum event rate for treatment is
      1/(NNT(T).RRR). The values that clinicians and patients use determine the
      threshold NNT and therefore also the minimum target event rate, without
      treatment, above which treatment is justified. Quantification of the determinants
      of the threshold NNT and of the minimum event rate to justify treatment can
      assist clinicians and patients in the explicit use of underlying values when
      making treatment decisions.

PMID- 11223324
TI  - Comparing discriminative validity between a disease-specific and a general health
      scale in patients with moderate asthma.
AB  - Health-related quality of life scales such as the Asthma Quality of Life
      Questionnaire and the Medical Outcomes Study Short-form General Health Survey SF
      36 have become important measures of health status in clinical asthma trials. The
      discriminative properties of these scales, however, have not been extensively
      evaluated and compared. The purposes of this study were to assess and compare
      scale and discriminative properties of the Asthma Quality of Life Questionnaire
      (AQLQ) and the SF-36 in a group of patients with moderate asthma using a patient
      rated global measure of disease activity as the criterion variable. Patients were
      interviewed in-person with a series of questionnaires including the AQLQ and the
      SF-36, and were also asked the global question "How active is your asthma now?"
      with possible responses of "extremely," "very," "moderately," "mildly" or "not
      active." Discriminative properties were determined using receiver operating
      characteristic (ROC) curves with responses to the global question as the
      criterion variable and mean domain scale scores as the independent variables.
      Relative validities for the AQLQ and SF-36 domains were also compared. A total of
      230 patients, mean age of 41 years, were enrolled. Scores were lower and ranges
      were narrower for the AQLQ compared to the SF-36. In general, the AQLQ and the SF
      36 were highly correlated, with r = 0.69 for the AQLQ overall score and the SF-36
      Physical Component Summary (PCS) score. According to ROC analyses, both scales
      had excellent discriminative properties; however the area under the ROC curve was
      higher for the AQLQ overall score (0.81) than for the PCS (0.75). When ranked
      according to ROC area, the symptoms domain (0.83) had the greatest area under the
      ROC curve, followed by the emotional (0.76) and activities (0.76) domains of the
      AQLQ. However, in some cases, the area under the curve was less for an AQLQ
      domain (for example, 0.71 for the environmental domain) than for SF-36 domains
      (for example, 0.75 for the role physical, and 0.75 for the social domain).
      Similarly, the AQLQ overall had a higher relative validity (5.2) compared to the
      PCS (2.2), and the symptoms domain of the AQLQ had the highest relative validity
      (6.0). Thus, both the Asthma Quality of Life Questionnaire and the SF-36 were
      able to characterize patients with moderate asthma in our cross-sectional study.
      In addition, both scales had strong discriminative properties when assessed with
      a global patient rating of current disease activity.

PMID- 11223325
TI  - The association between neck pain intensity, physical functioning, depressive
      symptomatology and time-to-claim-closure after whiplash.
AB  - Time-to-claim-closure is a common outcome in cohort studies of whiplash injuries.
      However, its relationship to health recovery is unknown. We investigated the
      association between neck pain, physical functioning, depressive symptomatology
      and time-to-claim-closure in a Saskatchewan cohort of 5398 whiplash claimants in
      1994-1995. Participants were surveyed five times over 1 year. In 1995, the
      insurance system changed from tort to no-fault, eliminating compensation for pain
      and suffering. Under tort, a 10-point increase in pain reduced the claim-closure
      rate by 13-24% while a 10-point increase in physical functioning increased it by
      17%. Depressive symptomatology reduced the claim-closure rate by 37%. Under no
      fault, a 10-point increase in pain reduced the claim-closure rate by 18% while a
      10-point increase in physical functioning increased it by 10-35%. The presence of
      depressive symptomatology reduced the claim-closure rate by 36%. The results
      suggests lower pain, better function and the absence of depressive symptoms are
      strongly associated with faster time-to-claim-closure and recovery after
      whiplash, independent of the insurance system.

PMID- 11223326
TI  - Prevalence of comorbidity in patients with a chronic airway obstruction and
      controls over the age of 40.
AB  - The goal of this study is to determine the prevalence of 23 common diseases in
      subjects with a chronic airway obstruction and in controls. All subjects with a
      known diagnosis by their general practitioner of asthma or chronic obstructive
      pulmonary disease (COPD), and who were 40 years and older were selected (n =
      1145). Subjects who were willing to participate (n = 591) and who appeared to
      have an irreversible airway obstruction (n = 290) were included. To recruit
      controls, a random sample was taken of 676 individuals who were 40 years and
      older and who were not diagnosed as having asthma or COPD by their general
      practitioner. Of these 676 individuals 421 were willing to participate. The
      presence of diseases was determined by using a questionnaire. One hundred and
      ninety-four subjects (73%) and 229 controls (63%) were shown to be suffering from
      one or more (other) diseases. In both groups, locomotive diseases, high blood
      pressure, insomnia and heart disease were most common. Locomotive diseases,
      insomnia, sinusitis, migraine, depression, stomach or duodenal ulcers and cancer
      were significantly more common in the subject group than in the control group.
      For both clinical and research purposes, it is important to consider the presence
      of diseases in patients with a chronic airway obstruction.

PMID- 11223327
TI  - The role of comorbidity in the assessment of intermittent claudication in older
      adults.
AB  - The prevalence of intermittent claudication (IC) in older adults by questionnaire
      is less than 5% while the prevalence of peripheral arterial disease (PAD) by non
      invasive testing is 2-4-fold higher. Comorbid conditions may result in under
      reporting intermittent claudication (IC) as assessed by the Rose Questionnaire.
      We examined characteristics of those who report leg pain in relationship to other
      comorbid conditions and disability in 5888 participants of the Cardiovascular
      Health Study (CHS). Older adults with exertional leg pain, not meeting criteria
      for IC, had a higher prevalence of PAD on non-invasive testing with the ankle-arm
      index than those without pain, as well as a higher prevalence of arthritis. The
      pattern of responses suggested that pain for both conditions was reported
      together. The Rose Questionnaire for IC is specific for PAD, but a negative
      questionnaire does not indicate a lack of symptoms, rather the presence of PAD
      along with other conditions that can cause pain.

PMID- 11223328
TI  - Glottic cancer in Ontario, Canada and the SEER areas of the United States. Do
      different management philosophies produce different outcome profiles?
AB  - We compared the management and outcome of glottic cancer in Ontario, Canada to
      that in the Surveillance, Epidemiology and End Results (SEER) Program areas in
      the United States to determine whether the greater use of primary radiotherapy
      with surgery reserved for salvage in Ontario was associated with similar survival
      and better larynx retention rates than the U.S. approach where primary surgery is
      used more often. Electronic, clinical and hospital data were linked to cancer
      registry data and supplemented by chart review where necessary. Initial treatment
      and survival in patients diagnosed in the SEER areas from 1988 through 1994 were
      compared to patients from Ontario diagnosed from 1982 through 1995. Actuarial
      laryngectomy rates were compared for patients over 65 at diagnosis in the two
      regions. Analyses were conducted over all cases and stratified by disease stage.
      In localized disease (T1 or T2), conservative treatment was the most common
      initial treatment in both regions, although total laryngectomy was used more
      often in SEER than Ontario (6.2% vs. 0.2%, respectively, P <.001). In advanced
      disease (T3 or T4), total laryngectomy was more commonly used as initial
      treatment in SEER (62.9% vs. 21.0% in Ontario, P < or =.001). Over all cases, the
      relative survival rate was 80% in Ontario at 5 years compared to 78% in SEER (P
      =.33). In localized disease, the relative survival rates were 4 to 5% higher in
      Ontario from the second year on, while in advanced disease 2 to 3% higher rates
      in SEER did not approach statistical significance. Actuarial laryngectomy rates
      at 3 years differed between the two regions, with a 4% higher rate in SEER (P
      =.01). In localized disease, 12.6% of Ontario patients had a laryngectomy by 3
      years postdiagnosis compared to 17.9% in SEER (P =.05). In advanced disease, the
      rates were 63.3% and 79.2%, respectively (P =.07). There are large differences in
      the management of glottic cancer between the SEER areas of the U.S. and Ontario
      and no evidence that a policy emphasizing radiotherapy with surgery reserved for
      salvage is associated with worse survival. Ultimate laryngectomy rates are lower
      in Ontario for localized disease and may be lower for advanced disease.
      Conservation treatment should be used for localized disease while the treatment
      decision in advanced disease may be especially sensitive to patient values for
      voice retention versus initial cure.

PMID- 11223329
TI  - White blood cell count: an independent predictor of coronary heart disease
      mortality among a national cohort.
AB  - An association between elevated white blood cell (WBC) count and coronary heart
      disease (CHD) mortality has been previously observed. However, the relationship
      between WBC count and CHD mortality independent of cigarette smoking and the
      possible interaction between WBC count and smoking remains unclear. We examined
      the association between WBC count and CHD mortality with Cox regression analyses
      of data from 8914 adults, aged 30-75, in the NHANES II Mortality Study (1976
      1992). Covariates included age, sex, race, education, physical activity, smoking
      status, hypertensive status, total serum cholesterol, body mass index,
      hematocrit, and history of cardiovascular disease, stroke, and diabetes. During
      17 follow-up years, there were 548 deaths from CHD (ICD-9 410-414) and 782 deaths
      from diseases of the heart (ICD-9 390-398, 402, 404, 410-414, 415-417, 420-429).
      Mean WBC count (x10(9) cells/L) was greater among persons who died from CHD (7.6
      vs 7.2, P <.001). Compared to persons with a WBC count <6.1, persons with a WBC
      count > 7.6 were at increased risk of death from CHD (relative risk = 1.4, 95%
      confidence interval = 1.1-1.8) after adjustment for smoking status and other CVD
      risk factors. Similar results were observed among nonsmokers (RR = 1.4, 95% CI =
      0.9-2.0). These results suggest that higher WBC counts are a predictor of CHD
      mortality independent of the effects of smoking and other traditional CVD risk
      factors, which may indicate a role for inflammation in the pathogenesis of CHD.
      Additional studies are needed to determine whether interventions to decrease
      inflammation can reduce the risk for CHD associated with elevated WBC.

PMID- 11223330
TI  - Endochondral ossification of costal cartilage is arrested after chondrocytes have
      reached hypertrophic stage of late differentiation.
AB  - Late cartilage differentiation during endochondral bone formation is a multistep
      process. Chondrocytes transit through a differentiation cascade under the
      direction of environmental signals that either stimulate or repress progression
      from one step to the next. In human costal cartilage, chondrocytes reach very
      advanced stages of late differentiation and express collagen X. However,
      remodeling of the tissue into bone is strongly repressed. The second hypertrophy
      marker, alkaline phosphatase, is not expressed before puberty. Upon sexual
      maturity, both alkaline phosphatase and collagen X activity levels are increased
      and slow ossification takes place. Thus, the expression of the two hypertrophy
      markers is widely separated in time in costal cartilage. Progression of
      endochondral ossification in this tissue beyond the stage of hypertrophic
      cartilage appears to be associated with the expression of alkaline phosphatase
      activity. Costal chondrocytes in culture are stimulated by parathyroid hormone in
      a PTH/PTHrP receptor-mediated manner to express the fully differentiated
      hypertrophic phenotype. In addition, the hormone stimulates hypertrophic
      development even more powerfully through its carboxyterminal domain, presumably
      by interaction with receptors distinct from PTH/PTHrP receptors. Therefore, PTH
      can support late cartilage differentiation at very advanced stages, whereas the
      same signal negatively controls the process at earlier stages.

PMID- 11223331
TI  - Cysteine proteinases in chondrosarcomas.
AB  - The aim of the present study was to define the role of cathepsins B, H, K, L and
      S in the pathogenesis of human chondrosarcomas. For this purpose 40 tumour
      samples obtained from 12 patients with the diagnosis of conventional
      chondrosarcoma were systematically investigated for the expression of cathepsin
      mRNAs by Northern hybridisation, and for immunohistochemical localisation of the
      proteins. Northern analysis demonstrated the highest levels of cathepsins B and L
      in a recurring grade 1 chondrosarcoma, and in a grade 3 chondrosarcoma and in
      fibrous histiocytomas. Increased expression of cathepsin K mRNA was seen in seven
      chondrosarcomas, as well as in control tumours; fibrous histiocytomas,
      osteosarcomas, enchondromas and a giant cell tumour of bone. Cathepsin L was
      immunolocalised within the large chondrocytes, while cathepsin K was
      predominantly localised in large multinucleated osteoclastic cells and in some
      hypertrophic chondrocytes. These results suggest that chondrosarcoma can be
      included in the growing list of tumours, where cathepsins may well be involved in
      tumour progression. The simultaneous upregulation of cathepsins B and L, together
      with matrix metalloproteinase-13, and the association of cathepsin K with
      negative prognostic parameters suggests that an aggressive biological behaviour
      of chondrosarcoma may be related to the synthesis of cysteine proteinases and
      activation of other proteolytic enzymes. If this turns out to be the case,
      cathepsin inhibitors could provide the much needed adjuvant therapy for
      chondrosarcomas.

PMID- 11223332
TI  - Type XIII collagen: a novel cell adhesion component present in a range of cell
      matrix adhesions and in the intercalated discs between cardiac muscle cells.
AB  - Recent analysis of type XIII collagen surprisingly showed that it is anchored to
      the plasma membranes of cultured cells via a transmembrane segment near its amino
      terminus. Here we demonstrate that type XIII collagen is concentrated in cultured
      skin fibroblasts and several other human mesenchymal cell lines in the focal
      adhesions at the ends of actin stress fibers, co-localizing with the known focal
      adhesion components talin and vinculin. This co-occurrence was also observed in
      rapidly forming adhesive structures of spreading and moving fibroblasts and in
      disrupting focal adhesions following microinjection of the Rho-inhibitor C3
      transferase into the cells, suggesting that type XIII collagen is an integral
      focal adhesion component. Moreover, it appears to have an adhesion-related
      function since cell-surface expression of type XIII collagen in cells with weak
      basic adhesiveness resulted in improved cell adhesion on selected culture
      substrata. In tissues type XIII collagen was found in a range of integrin
      mediated adherens junctions including the myotendinous junctions and costameres
      of skeletal muscle as well as many cell-basement membrane interfaces. Some cell
      cell adhesions were found to contain type XIII collagen, most notably the
      intercalated discs in the heart. Taken together, the results strongly suggest
      that type XIII collagen has a cell adhesion-associated function in a wide array
      of cell-matrix junctions.

PMID- 11223333
TI  - Decreased capacity of asthmatic bronchial fibroblasts to degrade collagen.
AB  - The mechanisms of fibrillar collagen accumulation in asthmatic bronchi remain
      unclear, an imbalance between synthesis and degradation of collagen may be
      implicated in this process. The aim of this study was to compare the capacities
      of normal (BNF) and asthmatic (BAF) bronchial fibroblasts to degrade collagen.
      Metalloproteinases and their inhibitors were measured by ELISA, types I and III
      procollagen synthesis was determined by liquid RIA and, finally, zymography was
      used to assess the presence of active and latent forms of MMPs. The capacity of
      fibroblasts to degrade collagen coated onto latex beads was evaluated by flow
      cytometry. Our results showed that MMP-2 secretion was significantly higher in
      BNF when compared to BAF and this was confirmed by gelatin zymography. In BNF
      culture, TIMP-1 and MMP-1 secretions positively correlated with types I and III
      procollagen synthesis. However, in BAF, this correlation was negative. This
      suggests that a balance exists between collagen synthesis and degradation in BNF
      and that this balance is compromised in BAF. On the other hand, BAF did show
      significantly reduced capacity to degrade collagen when compared to that of BNF.
      This reduced phagocytic activity was not associated with a decrease in collagen
      receptor expression. This study establishes for the first time that a
      relationship exists between metalloproteinases enzyme dysregulation and the
      reduced capacity of asthmatic bronchial fibroblast to degrade collagen. These
      events may shed light on why accumulation of collagen can be observed in
      asthmatic airways.

PMID- 11223334
TI  - Reduced hydrolysis of amelogenin may result in X-linked amelogenesis imperfecta.
AB  - Amelogenesis imperfecta (AI) is a group of inherited disorders with defective
      tooth enamel formation caused by various gene mutations. One of the mutations
      substitutes a cytidine to adenine in exon 6 of the X-chromosomal amelogenin gene,
      which results in a proline to threonine change in the expressed amelogenin. This
      transformation is four amino acids N terminal to the proteinase cleavage site in
      amelogenin for enamel matrix metalloproteinase-20 (MMP-20), also known as
      enamelysin. MMP-20 effects the release of tyrosine rich amelogenin peptide (TRAP)
      from amelogenin. This study evaluated the rate MMP-20 hydrolyzes the putative
      mutated amelogenin cleavage site. The proteolytic site was modeled as a substrate
      by two synthetic peptides, P1 (SYGYEPMGGWLHHQ) and M1 (SYGYETMGGWLHHQ), selected
      from residue 36-49 of the amino acid sequence for amelogenin and the respective X
      linked amelogenin mutant. Recombinant metalloproteinase-20 (rMMP-20) was used to
      digest the oligopeptides and the truncated peptides were separated by reversed
      phase HPLC and identified by mass spectrometry. The results demonstrate that both
      peptides are cleaved between tryptophan and leucine, matching the TRAP cutting
      site found in tooth enamel. However, the apparent first order rate of digestion
      of the mutation containing peptide by rMMP-20 was approximately 25 times slower
      than that of the non-mutated peptide. This study suggests that the reduced rate
      of TRAP formation due to a single amino acid substitution may alter enamel
      formation and consequently result in amelogenesis imperfecta.

PMID- 11223335
TI  - Stage-and tissue-specific expression of a Col2a1-Cre fusion gene in transgenic
      mice.
AB  - To achieve chondrocyte-specific deletion of floxed genes we generated a
      transgenic mouse line expressing the Cre recombinase under the control of the
      mouse type II collagen gene (Col2a1) regulatory regions. Northern and in situ
      hybridization analyses demonstrated the expression of the transgene (Col2a1-Cre)
      in cartilaginous tissues. To test the excision efficiency of Cre, the Col2a1-Cre
      strain was crossed with the ROSA26 reporter strain. LacZ staining of double
      transgenic mice revealed Cre activity in both chondrogenic and non-chondrogenic
      tissues. During early embryonic development (E9.5-11.5), LacZ expression was
      detected in tissues where the endogenous Col2a1 transcript is expressed such as
      the otic capsule, notochord, developing brain, sclerotome and mesenchymal
      condensations of future cartilage. At later stages, Cre activity was observed in
      all cartilaginous tissues with virtually 100% of chondrocytes being LacZ
      positive. These data suggest that the Col2a1-Cre mouse strain described here can
      be useful to achieve Cre-mediated recombination in Col2a1 expressing cells,
      especially in chondrocytes.

PMID- 11223336
TI  - Basement membrane and interstitial proteoglycans produced by MDCK cells
      correspond to those expressed in the kidney cortex.
AB  - Multiple proteoglycans (PGs) are present in all basement membranes (BM) and may
      contribute to their structure and function, but their effects on cell behavior
      are not well understood. Their postulated functions include: a structural role in
      maintaining tissue histoarchitecture, or aid in selective filtration processes;
      sequestration of growth factors; and regulation of cellular differentiation.
      Furthermore, expression PGs has been found to vary in several disease states. In
      order to elucidate the role of PGs in the BM, a well-characterized model of
      polarized epithelium, Madin-Darby canine kidney (MDCK) cells has been utilized.
      Proteoglycans were prepared from conditioned medium by DEAE anion exchange
      chromatography. The eluted PGs were treated with heparitinase or chondroitinase
      ABC (cABC), separately or combined, followed by SDS-PAGE. Western blot analysis,
      using antibodies specific for various PG core proteins or CS stubs generated by
      cABC treatment, revealed that both basement membrane and interstitial PGs are
      secreted by MDCK cells. HSPGs expressed by MDCK cells are perlecan, agrin, and
      collagen XVIII. Various CSPG core proteins are made by MDCK cells and have been
      identified as biglycan, bamacan, and versican (PG-M). These PGs are also
      associated with mammalian kidney tubules in vivo.

PMID- 11223337
TI  - Cell density regulates prolyl 4-hydroxylase activity independent of mRNA levels.
AB  - In embryonic avian tendon, cell density regulates collagen production. This
      control is propagated through the alpha-subunit of prolyl 4-hydroxylase where
      protein levels were previously shown to rise fivefold with increasing cell
      density. In contrast, mRNA levels are now shown not to change by both Northern
      and RNAse protection assays. This lack of increase contrasts with previous
      reports as does the mRNA length: this is 50% larger as confirmed by sequencing
      the 3' end. Alternative sites for cell density regulation of the enzyme could
      rely on its sensitivity to sulfhydryl groups. Using a fluorescent sulfhydryl
      probe as well as a sulfhydryl inhibitor, one observes a strong cell density
      response, supporting the hypothesis that cellular redox potential could alter
      protein stability.

PMID- 11223338
TI  - Analysis of the promoter region of human cartilage oligomeric matrix protein
      (COMP).
AB  - Cartilage oligomeric matrix protein (COMP) is an extracellular matrix protein
      expressed in cartilage, ligament, and tendon. The importance of COMP in the
      matrix of these cells is underscored by the discovery that mutations in COMP
      cause the skeletal dysplasias, pseudoachondroplasia (PSACH) and multiple
      epiphyseal dysplasia (EDM1). Here, we present the first report on the analysis of
      the human COMP promoter region in cartilage, ligament, and tendon cells. A 1.7-kb
      region of the COMP promoter has been cloned and sequenced and no TATA or CAAT
      boxes were found. Primer extension identified multiple transcription start sites.
      All four transcription start sites were utilized in chondrocytes with only three
      of them utilized in tendon and ligament cells. Differential regulation was
      observed for different parts of this 1.7-kb region with the 370-bp proximal
      region conveying the strongest promoter activity. The highest activity was
      observed in tendon and ligament. Finally, we provide evidence that the DNA
      binding protein SP1 plays a role in the regulation of COMP expression. These
      results indicate that COMP expression within these cells is regulated in a unique
      manner that differs from the expression of other extracellular matrix genes.

PMID- 11223339
TI  - Secretion pattern, ultrastructural localization and function of extracellular
      matrix molecules involved in eggshell formation.
AB  - The chicken eggshell is a composite bioceramic containing organic and inorganic
      phases. The organic phase contains, among other constituents, type X collagen and
      proteoglycans (mammillan, a keratan sulfate proteoglycan, and ovoglycan, a
      dermatan sulfate proteoglycan), whose localization depends on a topographically
      defined and temporally regulated deposition. Although the distribution of these
      macromolecules in the eggshell has been well established, little is known about
      their precise localization within eggshell substructures and oviduct cells or
      their pattern of production and function during eggshell formation. By using
      immunofluorescent and immuno-ultrastructural analyses, we examined the
      distribution of these macromolecules in oviduct cells at different post
      oviposition times. To understand the role of proteoglycan sulfation on eggshell
      formation, we studied the effects of inhibition of proteoglycan sulfation by
      treatment with sodium chlorate. We showed that these macromolecules are produced
      by particular oviduct cell populations and at precise post-oviposition times.
      Based on the precise ultrastructural localization of these macromolecules in
      eggshell substructures, the timing of the secretion of these macromolecules by
      oviduct cells and the effects on eggshell formation caused by the inhibition of
      proteoglycan sulfation, the putative role of mammillan is in the nucleation of
      the first calcite crystals, while that of ovoglycan is to regulate the growth and
      orientation of the later forming crystals of the chicken eggshell.

PMID- 11223340
TI  - Changes in leucine-rich repeat proteoglycans during maturation of the bovine
      growth plate.
AB  - The primary growth plate of the fetal bovine tibia was studied in order to
      determine whether changes in the structure, abundance and expression of the
      leucine-rich repeat proteoglycans were occurring during tissue maturation from
      reserve cartilage to hypertrophic cartilage. The proteoglycans under study were
      decorin, biglycan, fibromodulin and lumican. Decorin was readily detectable in
      both the reserve and proliferating zones of the growth plate, but its abundance
      decreased markedly in the zones of maturation and hypertrophy where it could not
      be detected under the same conditions of analysis. In contrast to decorin,
      fibromodulin and biglycan could be detected throughout the growth plate, though
      their abundance was decreased in the proliferative and hypertrophic zones. Unlike
      the other proteoglycans, lumican could not be detected throughout the growth
      plate. At the message level, the expression of decorin shows a similar trend to
      that of protein abundance in the extracellular matrix, with its expression
      dropping markedly in the proliferative and hypertrophic zones. In the case of
      both biglycan and fibromodulin, message expression continued at a similar level
      throughout the growth plate. Thus, the leucine-rich repeat proteoglycans are
      different in the way they behave during growth plate maturation.

PMID- 11223341
TI  - SPARC, a matricellular protein: at the crossroads of cell-matrix communication.
AB  - SPARC is a multifunctional glycoprotein that belongs to the matricellular group
      of proteins. It modulates cellular interaction with the extracellular matrix
      (ECM) by its binding to structural matrix proteins, such as collagen and
      vitronectin, and by its abrogation of focal adhesions, features contributing to a
      counteradhesive effect on cells. SPARC inhibits cellular proliferation by an
      arrest of cells in the G1 phase of the cell cycle. It also regulates the activity
      of growth factors, such as platelet-derived growth factor (PDGF), fibroblast
      growth factor (FGF)-2, and vascular endothelial growth factor (VEGF). The
      expression of SPARC in adult animals is limited largely to remodeling tissue,
      such as bone, gut mucosa, and healing wounds, and it is prominent in tumors and
      in disorders associated with fibrosis. The crystal structure of two of the three
      domains of the protein has revealed a novel follistatin-like module and an
      extracellular calcium-binding (EC) module containing two EF-hand motifs. The
      follistatin-like module and the EC module are shared by at least four other
      proteins that comprise a family of SPARC-related genes. Targeted disruption of
      the SPARC locus in mice has shown that SPARC is important for lens transparency,
      as SPARC-null mice develop cataracts shortly after birth. SPARC is a prototypical
      matricellular protein that functions to regulate cell-matrix interactions and
      thereby influences many important physiological and pathological processes.

PMID- 11223342
TI  - A method for preventive cardiology in children.
AB  - There are clear indications for prevention of atherosclerotic disease to begin in
      childhood. Optimal primary prevention will utilize a public health strategy. For
      children with elevated risk for atherosclerotic disease a clinically based
      prevention program is helpful. The indications for and an approach to the
      pediatric preventive cardiology clinic are reviewed.

PMID- 11223343
TI  - Obesity in the pediatric patient: cardiovascular complications.
AB  - The prevalence and severity of obesity are increasing in children and
      adolescents. This raises concerns about the accompanying cardiovascular
      complications. Such complications include hypertension, dyslipidemia, type II
      diabetes which may accelerate vascular disease, left ventricular hypertrophy and
      pulmonary hypertension due to obstructive sleep apnea. The evaluation of an obese
      child or adolescent should include careful consideration of these possible
      cardiovascular complications. If they are present, treatment should be directed
      at both obesity and the risk factor abnormality. This treatment may be important
      for prevention of future cardiovascular morbidity and mortality. In addition,
      research is necessary to better understand the mechanisms by which obesity
      increases the risk of cardiovascular disease.

PMID- 11223344
TI  - Insulin resistance and cardiovascular risk in the pediatric patient.
AB  - The insulin resistance syndrome, a cluster of potent risk factors for
      atherosclerotic cardiovascular disease and type 2 diabetes in adults, is composed
      of hyerinsulinemia, obesity, hypertension and hyperlipidemia. In addition, left
      ventricular hypertrophy and its precursor increased left ventricular mass, is
      known to be a powerful predictor of adverse cardiovascular events, both as an
      independent risk factor and by association with the insulin resistance syndrome.
      Obesity appears to have a major role in the relations between the components of
      the insulin resistance syndrome, and their association with increased heart mass.
      Of significant impact in the adult population, atherosclerotic cardiovascular
      disease and death are rarely seen in the young, but the pathologic processes and
      risk factors associated with its development have been shown to begin during
      childhood. Recent studies revealed the presence of components of the insulin
      resistance syndrome also in children and adolescents, however, their associations
      are not well understood. A direct link between obesity and insulin resistance has
      also been reported in the young, as has the link between insulin resistance and
      abnormal lipid profile. There is an increasing amount of data to show that being
      overweight during childhood and adolescence is significantly associated with
      insulin resistance, abnormal lipids and elevated blood pressure in young
      adulthood. Weight loss in these situations results in a decrease in insulin
      concentration and an increase in insulin sensitivity toward normalcy. Moreover,
      it has been determined that increased left ventricular mass is present in
      childhood, and is related to other risk factors, namely obesity and insulin
      resistance. Based on current knowledge, it is reasonable to suggest that weight
      control, and lifestyle modification, could alter the incidence of the syndrome of
      insulin resistance, and improve the risk profiles for cardiovascular disease as
      children make the transition toward adolescence and young adulthood.

PMID- 11223345
TI  - Evaluation and management of hypertension in childhood.
AB  - Hypertension, a relatively uncommon problem in childhood except in certain groups
      of children, is an important cardiovascular risk factor that can have significant
      health implications, especially the tendency for an elevated blood pressure in
      childhood to predict the development of adult hypertension. Common causes of
      childhood hypertension include renal and cardiac disease, as well as essential
      hypertension in adolescents. Given these factors, it is usually possible to
      evaluate the hypertensive child in a focused manner that should reveal not only
      the underlying cause of hypertension, but also its severity. Treatment should
      incorporate non-pharmacologic approaches as well as antihypertensive medications,
      and should take into account other cardiovascular risk factors such as
      hyperlipidemia. This review highlights these and other important issues in the
      evaluation and management of hypertensive children, and provides practical
      guidance to the practitioner involved in caring for such patients.

PMID- 11223346
TI  - Prevention of essential hypertension in minority populations.
AB  - The precursors of essential hypertension (EH) begin in childhood. If the etiology
      of the evolution of EH were discovered, interventions may be developed to lead to
      the primary prevention of EH. In particular, one ethnic group, African-Americans
      (Blacks), are at increased risk of development of EH in adulthood. Hemodynamic
      changes in response to stressors are termed measures of cardiovascular reactivity
      (CVR). Ethnic difference in CVR are known to exist; are these markers or
      mechanisms of EH evolution? Investigations are underway to discover the
      mechanism(s) of the excessive vasoconstriction which appears to be characteristic
      of the CVR responses in Blacks. These may lead to the pharmacologic, or non
      pharmacologic, interventions which may be initiated in childhood and prevent EH
      in adults.

PMID- 11223347
TI  - Active and passive tobacco exposure.
AB  - Both passive and active exposure to tobacco smoke have adverse cardiovascular
      consequences for children and adolescents. Smoking as a habit begins in mid
      adolescence and is perpetuated by the highly addictive nature of nicotine.
      Smoking has been associated with decreased life expectancy from all causes and
      early atherogenesis. The physiologic effects of active, and possibly passive
      smoke exposure include endothelial injury, increased oxidizability of LDL
      cholesterol, lower HDL cholesterol, impaired exercise performance, and altered
      oxygen delivery. Physician roles have been limited to research into the harmful
      nature of tobacco in the past, but new roles in advocacy against tobacco
      companies and the treatment of nicotine addiction are evolving.

PMID- 11223348
TI  - The role of physical activity and fitness in children in the prevention of adult
      cardiovascular disease.
AB  - Research data in adults have provided convincing evidence that regular exercise
      creates a protective effect against the complications of coronary artery disease.
      Given that the atherosclerotic process begins during the pediatric years,
      improved physical activity and fitness has been promoted in children and
      adolescents as a means of preventing cardiovascular disease in adulthood.
      Although intuitively compelling, direct proof of this rationale for improving
      exercise habits of children is not available. Scientific data examining the
      effects of activity and fitness on coronary artery disease risk factors in the
      growing years do provide some evidence that promoting exercise in children might
      serve as a means of preventing future cardiovascular disease.

PMID- 11223349
TI  - Management of hyperlipidemia in children.
AB  - Atherosclerosis is a major cause of death and disability in adults. Recent
      investigations suggest that although cardiac end-points such as myocardial
      infarction and strokes mainly occur in middle-age and older subjects, the
      pathological basis for atherosclerosis begins in childhood. Hypercholesterolemia
      is one of the most important risk factors for atherosclerosis in adults and
      elevated cholesterol in children is associated with sub-clinical deposition of
      lipids in the aorta and coronary arteries. This report summarizes an approach to
      the diagnosis and treatment of hyperlipidemia in children. Based on guidelines
      from the National Cholesterol Education Program, children over 2 years of age
      should be screened for hypercholesterolemia if there is a family history of
      premature heart disease or hyperlipidemia. Therapy must be individualized. The
      majority of children with hyperlipidemia should be managed with a low-saturated
      fat and low-cholesterol diet. Children over 10 years of age with severe
      elevations of LDL-cholesterol and who come from high-risk families may be
      considered for more aggressive dietary therapy or medication in some cases. This
      is especially true for children with inherited disorders of lipid metabolism such
      as LDL-receptor deficiency. By identifying high-risk children and instituting
      therapy during childhood it is hoped that premature onset of adult coronary heart
      disease can be delayed or avoided altogether.

PMID- 11223350
TI  - The role and clinical applications of bioactive lysolipids in ovarian cancer.
AB  - OBJECTIVE: To review the current understanding of the role of bioactive
      lysolipids in ovarian cancer and their potential clinical applications. METHODS:
      A MEDLINE search and our own work, including some unpublished work, are the major
      sources of the review. The MEDLINE search terms used included lysophosphatidic
      acid, lysophophatidylcholine (LPC), lysophosphatidylinositol (LPI), sphingosine-1
      phosphate, and sphingosylphosphorylcholine (SPC). RESULTS: Elevated lysolipid
      levels were detected in plasma and ascites samples from patients with ovarian
      cancer compared with samples from healthy controls or patients with nonmalignant
      diseases. These lysolipids regulate growth adhesion, production of angiogenic
      factors, and chemotherapeutic drug resistance in ovarian cancer cells. Ovarian
      cancer cells were likely to be at least one of the sources for elevated lysolipid
      levels in the blood and ascites of patients with ovarian cancer. CONCLUSIONS:
      Bioactive lysolipid levels might be sensitive markers for detecting gynecologic
      cancers, particularly ovarian cancer. The prognostic value of lysolipids in
      ascites is worth further investigation. Bioactive lysolipid molecules can affect
      both the proliferative and metastatic potentials of ovarian cancer cells;
      therefore, regulation of the production or degradation of these lipids and
      interception of the interaction between these lipids and their receptors could
      provide novel and useful preventative or therapeutic measures.

PMID- 11223351
TI  - Inpatient monitoring on an outpatient basis: managing hypertensive pregnancies in
      the community using automated technologies.
AB  - Automated measurement of blood pressure and urinalysis is reviewed, and the
      strengths and weaknesses of these devices are compared with conventional
      techniques. The few early reports of such management strategies are reviewed with
      emphasis on the advantages of automated monitoring. The article concludes with a
      review of published pilot data in this field and places those findings in the
      context of recent recommendations for the development of obstetric care in the
      United Kingdom.

PMID- 11223352
TI  - Differential effects of endothelin A and B receptor antagonism on fetal growth in
      normal and nitric oxide-deficient rats.
AB  - OBJECTIVE: To determine the role of endothelin (ET) in fetal and placental growth
      in rats with and without long-term nitric oxide synthase (NOS) inhibition.
      METHODS: Pregnant rats were treated with N(omega)-nitro-L-arginine methyl ester
      (L-NAME) or saline and with one of three ET receptor antagonists or vehicle. The
      antagonists included A-182086 (nonselective) as well as A-127722 and FR-139317
      (both ET(A) selective). Treatment was begun on day 14 of gestation. On
      gestational day 21, a hysterotomy was done. Litter size was recorded, and
      viability and fetal and placental weights were determined. Results were analyzed
      by analysis of variance or by a Kruskal-Wallis nonparametric analysis. RESULTS:
      In the absence of L-NAME, fetal and placental weights were not affected by ET(A)
      selective antagonism but were significantly decreased by nonselective receptor
      antagonism (P <.001 and P <.05 for fetal and placental weights, respectively).
      Infusion of L-NAME resulted in fetal and placental growth restriction (P <.001).
      In the setting of L-NAME infusion, fetal and placental weights were increased by
      the ET(A)-selective antagonists (P <.01) but not by the nonselective antagonist,
      compared with weights from animals treated with L-NAME alone. There were more
      fetal deaths with L-NAME treatment (P <.05), but their occurrence was not
      significantly affected by any of the ET receptor antagonists. CONCLUSIONS:
      Endothelin-A antagonism alone did not affect fetal or placental growth, whereas
      combined ET(A) plus ET(B) antagonism produced fetal and placental growth
      restriction. In the setting of long-term NOS inhibition, ET(A)-selective
      antagonism improved fetal and placental growth, whereas antagonism of both ET(A)
      and ET(B) receptors did not. Endothelin contributes to NOS inhibition-induced
      growth restriction acting through the ET(A) receptor.

PMID- 11223353
TI  - Maternal basic fibroblast growth factor serum levels are associated with
      pregnancy-induced hypertension.
AB  - OBJECTIVE: To test the hypothesis that serum levels of basic fibroblast growth
      factor (bFGF) are altered among women with pregnancy-induced hypertension (PIH)
      and are associated with disease severity. METHODS: We evaluated serum levels of
      bFGF in 46 women with PIH, 46 age- and parity-matched healthy pregnant women, and
      46 healthy nonpregnant controls. Enzyme-linked immunosorbent assays were used to
      determine serum levels of bFGF. Results were correlated to clinical data.
      RESULTS: The overall mean serum levels of bFGF were 3.2 (standard deviation [SD]
      9.3) micromol/L. Mean serum levels of bFGF in normal controls, healthy pregnant
      women, and women with PIH were 0 (SD 0) micromol/L, 2.6 (SD 6.3) micromol/L, and
      6.8 (SD 13.8) micromol/L, respectively (P =.003) for normal controls compared
      with healthy pregnant women and P <.001 for healthy pregnant women compared with
      women with PIH). In a univariate logistic regression model bFGF showed a
      significant influence on the odds of presenting with PIH compared with healthy
      pregnant women (P =.002). The mean serum levels of bFGF in women with severe PIH
      and in women with mild PIH were 4.4 (SD 10.6) micromol/L and 9.5 (SD 17.3)
      micromol/L, respectively (P =.1). In a univariate logistic regression model bFGF
      did not reveal a significant influence on the odds of developing severe PIH (P
      =.3). CONCLUSIONS: Elevated serum levels of bFGF are associated with PIH, but
      bFGF does not seem to be a useful prognostic parameter for severe PIH.

PMID- 11223355
TI  - Plasma from preeclamptic women stimulates decidual endothelial cell growth and
      prostacyclin but not nitric oxide production: close correlation of prostacyclin
      and thromboxane production.
AB  - OBJECTIVE: To examine the effect of plasma from preeclamptic women on production
      of the vasoactive substances prostacyclin, thromboxane, nitric oxide, and cyclic
      guanosine monophosphate (cGMP) by decidual endothelial cells; to determine any
      effects on cell growth and health; and to examine whether cells from preeclamptic
      women are activated compared with cells from normal women. METHODS: Decidual
      endothelial cells from normal and preeclamptic women were incubated for 24 hours
      in media containing 10% plasma from preeclamptic women or matched normal women.
      Prostacyclin and thromboxane production was measured, as was nitric oxide and
      cGMP production after a further 45-minute generation period in 2% test plasma.
      Cell numbers and lactate dehydrogenase release were also determined. RESULTS: In
      plasma from preeclamptic women, cells grew significantly faster (P <.05),
      prostacyclin production was increased (P <.05), and lactate dehydrogenase release
      was reduced (P <.01). Production of thromboxane, nitric oxide, and cGMP was not
      significantly affected. Decidual endothelial cells from preeclamptic women had
      increased growth (P <.0001) and produced more prostacyclin (P <.05) and nitric
      oxide (P <.001) than normal decidual endothelial cells. There were highly
      significant correlations between prostacyclin and thromboxane production for
      incubations in plasmas from preeclamptic women and between background levels of
      prostacyclin in each plasma from preeclamptic women and the prostacyclin produced
      in incubations containing that plasma (P <.0001). CONCLUSION: We found that
      plasma from preeclamptic women contained a factor that stimulated endothelial
      cell growth and regulated production of related amounts of prostacyclin and
      thromboxane. The plasma level of this factor appeared to be related to background
      levels of prostacyclin. The results also indicated that decidual endothelial
      cells from preeclamptic women were in a relatively activated state.

PMID- 11223354
TI  - Maternal serum transforming growth factor beta-2 in preeclampsia and eclampsia, a
      potential biomarker for the assessment of disease severity and fetal outcome.
AB  - OBJECTIVE: The emerging role of transforming growth factor beta in hypertension,
      kidney disease, and trophoblast differentiation promoted our interest in
      evaluating the clinical value of assaying maternal serum TGF-beta2 levels in
      pregnancies complicated by preeclampsia and eclampsia. We wished to determine
      these levels in relation to the severity of the disease, the degree of renal
      involvement, and fetal outcome. METHODS: A prospective study was carried out in
      50 pregnant patients with preeclampsia (PE) and eclampsia and these women were
      compared to 20 pregnant normotensive controls. Preeclamptic patients were
      subdivided into 20 cases of mild PE, 20 cases of severe PE, and 10 cases of
      eclampsia. Maternal serum levels of TGF-beta2 were determined in all cases by
      enzyme immunoassay. Maternal serum creatinine and uric acid were measured,
      together with an assessment of fetal well being, using the Biophysical Profile
      Score. RESULTS: Maternal serum TGF-beta2 levels were significantly increased in
      cases of severe preeclampsia and eclampsia compared to controls. This increase
      was positively correlated with elevated levels of serum creatinine and uric acid,
      as well as poor biophysical profile scores (BPS), and low birth weight (LBW).
      CONCLUSION: Measurement of maternal serum TGF-beta2 levels in preeclampsia may be
      a useful biomarker for the assessment of the severity of disease and fetal
      outcome in PE.

PMID- 11223356
TI  - The preterm prediction study: maternal serum relaxin, sonographic cervical
      length, and spontaneous preterm birth in twins.
AB  - OBJECTIVE: The risk of spontaneous preterm birth has been related to decreased
      cervical length and to increased serum relaxin. To explore a relationship between
      these findings, we used data collected from two prior studies to correlate
      relaxin levels with cervical length and risk of spontaneous preterm birth in
      women with twin pregnancies. METHODS: In a secondary analysis of data collected
      in two previous observational studies of risk factors for preterm birth, relaxin
      levels in maternal serum and cervical length were measured at 24 (n= 188) and 28
      (n= 145) weeks in women with spontaneous twin pregnancies. Relaxin, as a
      continuous variable, was related by logistic regression analysis to risk of
      spontaneous preterm birth before 37, 35, and 32 weeks' gestation, and by Spearman
      correlation coefficients to cervical length at 24 and 28 weeks. Cervical length
      at 24 weeks was known to be correlated with spontaneous preterm birth before 37,
      35, and 32 weeks (P =.03,.01, and.002, respectively) in this study population.
      RESULTS: Cervical length did not correlate with relaxin levels at 24 (P=.601) or
      28 (P=.304) weeks. Relationships between relaxin and spontaneous preterm birth
      were observed at 24 weeks for births before 37 weeks (odds ratio [OR] 1.56, 95%
      confidence interval [CI] 1.00, 2.44; P=.05), and at 28 weeks for births before 35
      weeks (OR 1.97, 95% CI 1.05, 3.70; P=.034) and 32 weeks (OR 2.43, 95% CI 1.01,
      5.83; P=.048). CONCLUSION: The absence of an association between relaxin and
      cervical length suggests that increased relaxin does not explain the inverse
      correlation between cervical length and spontaneous preterm birth in women with
      spontaneous twin pregnancies.

PMID- 11223357
TI  - Maternal serum leptin concentrations do not correlate with cord blood leptin
      concentrations in normal pregnancy.
AB  - OBJECTIVE: To determine whether there is a difference in maternal leptin
      concentration and cord blood concentration, consistent with the hypothesis of a
      noncommunicating, two-compartement model of fetoplacental leptin regulation.
      METHODS: Blood samples were collected from 139 women, identified as having an
      uncomplicated pregnancy, from an antecubital vein at delivery. Cord blood samples
      were taken from the umbilical vein. Leptin was measured by radioimmunoassay, and
      its relationship to fetal and maternal anthropometrics was assessed by Spearman
      correlation. Differences in maternal and cord blood leptin levels between male
      and female infants were tested with the Mann-Whitney Utest. Maternal and cord
      blood leptin were compared by the Wilcoxon signed rank test. The outcome measures
      were maternal and cord blood leptin at delivery, fetal birth weight, length,
      weight/length ratio, and ponderal index, maternal prepregnancy body mass index,
      pregnancy weight gain, relative weight gain, and body mass index at delivery.
      RESULTS: No correlations were found between maternal and cord blood leptin
      concentrations. Fetal leptin level correlated with birth weight (rho = 0.665; P
      <.0001), length (rho = 0.490; P <.0001), ponderal index (rho = 0.260; P =.002),
      and weight/length ratio (rho = 0.625; P <.0001). Median leptin concentrations
      were higher in female (9.3 ng/mL, range 1.5-34.4 ng/mL) than in male (8.2 ng/mL,
      range 1.6-38.3 ng/mL) neonates, but this difference was statistically not
      significant. Logistic regression analysis showed a significant influence on
      umbilical venous leptin concentration for birth weight (P <.0001) but not for
      gender. Maternal leptin concentrations were significantly higher than cord leptin
      concentrations (P <.0005 for the male and female neonates and the entire group).
      CONCLUSION: There was no correlation between maternal and cord leptin, which
      supports the hypothesis of a noncommunicating, two-compartment model of
      fetoplacental leptin regulation.

PMID- 11223358
TI  - Four-channel tocography in uneventful pregnancies: a prospective study in
      primigravidas and multigravidas.
AB  - OBJECTIVE: The simultaneous recording of external uterine pressure in four
      locations on the abdominal wall with four-channel-tocography provides new ways to
      describe the dynamics of uterine activity. METHODS: Fifty-eight healthy
      primigravidas and 25 healthy multigravidas were studied prospectively with four
      channel tocography during the course of pregnancy. Starting at 21 weeks'
      gestation, the following five intervals were defined: 21-24, 25-28, 29-32, 33-36
      and more than 37 completed weeks. Eligibility criteria included informed consent,
      no history of malformations of the uterus, and no previous preterm deliveries.
      Patients were excluded for the following reasons: medication for preterm labor,
      cerclage, placenta previa, delivery before 37 weeks' gestation, less than three
      measurements completed, and patient's withdrawal of consent. RESULTS: The median
      contraction frequency per hour was six for primigravidas and five for
      multigravidas, without significant correlation with gestational age. At all time
      periods studied, the median rate of global contractions developing simultaneously
      in at least three uterine segments was less than 15%; however, it was
      significantly higher in primigravidas than in multigravidas (14% versus 4%, P
      <.001). Both groups had more activity in the right upper quadrant of the uterus
      shortly before delivery. CONCLUSION: Four-channel tocography provided insight
      into uterine activity patterns and might enable obstetricians to select
      clinically relevant contractions for further treatment.

PMID- 11223360
TI  - Systemic benefits of cyclic ovarian function.
AB  - OBJECTIVE: To consider the systemic benefits of cyclic ovarian function. METHODS:
      Review and interpretation of extant data and concepts, with a focus on the
      physiologic impact of gonadal steroid exposures upon key nonreproductive target
      tissues in women. RESULTS: The role of cyclic ovarian function in reproductive
      processes such as menstruation, folliculogenesis, and conception is well
      understood. Less is known about the impact of the characteristic sex steroid
      fluctuations associated with ovulatory menstrual cycles upon what are typically
      viewed as nonreproductive tissues, such as the limbic lobe and cerebral cortex.
      The explosion in knowledge regarding the molecular mechanisms of steroid action
      has expanded our appreciation of the complex and often subtle nature of this
      impact. CONCLUSIONS: A clear understanding of the systemic benefits of cyclic
      ovarian function is required to advise patients adequately about the risks and
      benefits of exogenous hormone use for the remediation or induction of anovulatory
      states. The inherent complexity of steroid hormone action coupled with the
      recognition that there is a long list of reproductive and nonreproductive target
      tissues obviates simple statements about the risks and benefits of hormonal
      manipulation and anovulatory states.

PMID- 11223361
TI  - Systemic adversities of ovarian failure.
AB  - Normal human ovarian function is a complex process. Ovarian failure can lead to
      lack of not only female estrogenic steroids, but also progestins, androgens,
      protein hormones and growth factors, and oocytes themselves. In addition, the
      process is not abrupt or immediate but often intermittent, leading to
      difficulties in diagnosis and treatment. The systemic impact of ovarian failure
      depends on the timing of ovarian failure (before or after puberty, family
      building, and age-expected menopause) as well as on the specific compartments
      that are compromised. Although the impact of reduced estrogen secretion is
      generally known, the systemic effects of the losses of pregnancy, progestins,
      androgens, and other ovarian products remain poorly understood. Finally, the
      underlying diseases causing premature ovarian failure may result in additional
      systemic symptoms. In summary, cessation of ovarian function has many physiologic
      implications for women that extend far beyond the loss of estrogen secretion.

PMID- 11223362
TI  - Research on the mechanisms of premature ovarian failure.
AB  - As many as 5% of women may experience menopause at or before age 45 (POF). Four
      causes are known for POF: (1) Genetic. Clear-cut X chromosome deletions,
      particularly those in the critical region, result in truncation of reproductive
      lifespan. Creation of a central genetic data bank for women with POF may assist
      in defining the genetic contribution to this condition. (2) Autoimmune. POF
      coexists with virtually all of the permutations of the autoimmune polyglandular
      failure syndromes, most often in linkage with antithyroid and antiadrenal
      antibodies. (3) Iatrogenic. Iatrogenic POF results from repeated ovarian
      surgeries, or from the underlying disease that led to the surgery. (4)
      Environmental. Environmental toxicants are difficult to pinpoint, but evidence
      suggests that galactose consumption is linked to early menopause. We investigated
      the possibility that POF represented premature endocrine aging that was
      generalized, rather than specifically targeted to the ovary. Detailed
      investigation of the gonadotropin-releasing hormone-luteinizing hormone system,
      the somatotrophic axis, the adrenal glucocorticoid and androgen axes, and the
      prolactin axis have led us to conclude that women with POF are not prematurely
      aged in any endocrine system other than the ovary. Basic research on how the
      ovary interacts with the immune system, particularly in the early stages of
      oogenesis, how the oocyte and follicle interact in fetal life, and how follicles
      might be protected from damage in the case of immune self-attack are all fruitful
      avenues of clinically applicable work that may lead to treatments for this most
      vexing reproductive disorder.

PMID- 11223363
TI  - Role of growth factors in ovary organogenesis.
AB  - The organogenesis of the ovary encompasses the formation of a great variety of
      structures, both germinal and nongerminal. Primordial follicle (PF) formation is
      of the utmost importance because PFs are obligatory for the reproductive cycle
      and female fertility. The major events involved in PF formation are described.
      Areas that could benefit from more investigation are discussed. The working
      premise is that the number of PFs formed during normal ovary organogenesis varies
      from one female to the next (ranging from high to low), and that this variability
      is revealed by the timing of age-related infertility and the menopause. Implicit
      in this supposition is the concept that anything that alters the sequence of
      events involved in the process of PF development will have important consequences
      on female fertility and health.

PMID- 11223364
TI  - Cellular interactions that control primordial follicle development and
      folliculogenesis.
AB  - Specific factors that mediate local cell--cell interactions in the ovary related
      to the initiation and progression of follicle development will be discussed.
      Recently, several factors produced locally by the primordial follicle have been
      shown to induce primordial follicle development from a quiescent state to promote
      follicle development. Kit ligand/stem cell factor (KL/SCF) produced by the
      immature granulosa cells appears to promote theca cell organization. Basic
      fibroblast growth factor produced predominately by the oocyte, but by all cells
      at reduced levels, also was found to induce primordial follicle development
      similar to KL. It is likely that numerous locally produced factors will mediate
      cellular interactions and interact between each other to control the induction of
      primordial follicle development and influence processes such as the onset of
      puberty and menopause. After follicle development has been induced, theca cells
      and granulosa cells interact through classical mesenchymal-epithelial type
      interactions to influence the progression of follicle development. Mesenchymally
      derived theca cells have been shown to produce transforming growth factor alpha
      (TGF-alpha), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF),
      and transforming growth factor beta to regulate granulosa cell growth and
      function. The epithelial granulosa cells have been show to produce KL/SCF that
      can feed back on the theca cells to regulate theca cell growth and stimulate the
      production of the theca cell factors (TGF-alpha, KGF, and HGF). Therefore, a
      positive feedback loop between the theca cells and granulosa cells appears to
      exist to promote the dramatic cell growth required during folliculogenesis.
      Interestingly, hormones such as estrogen and gonadotropins stimulate the
      expression of these paracrine growth factors. Therefore, the actions of hormones
      to stimulate follicle development and growth are mediated in part through
      altering these local cell--cell interactions. In summary, the locally produced
      paracrine factors that mediate cell-cell interactions involved in primordial
      follicle development and the progression of follicle development during
      folliculogenesis are starting to be elucidated.

PMID- 11223365
TI  - Graafian follicle function and luteinization in nonprimates.
AB  - The ovarian follicle has two major functions. It provides for the maturation and
      release of a fertilizable oocyte. It also forms the corpus luteum, which promotes
      and maintains implantation of the embryo. For these processes to occur, the
      follicle has to grow, ovulate, and luteinize. The transition of granulosa cells
      to luteal cells requires rapid changes in the expression of specific genes. In
      this transition, many genes expressed in granulosa cells are turned off, whereas
      the genes controlling terminal differentiation to luteal cells are induced. Of
      major importance are changes in the regulation of specific kinase cascades that
      regulate proliferation and differentiation as well as specific protease cascades
      that control the remodeling of the follicle during ovulation and formation of the
      corpus luteum. The dramatic reprogramming of gene expression in granulosa cells
      leading to that of luteal cells is complete within 5 to 7 hours and is
      irreversible.

PMID- 11223366
TI  - Modifications in gonadotropin signaling: a key to understanding cyclic ovarian
      function.
AB  - The enigma in understanding the regulation of ovarian function throughout the
      menstrual cycle is that both follicle-stimulating hormone (FSH) and luteinizing
      hormone (LH) act on the ovary, at least in part through the cyclic adenosine
      monophosphate (cAMP) intracellular signaling pathway. If cAMP is a common
      intracellular messenger of gonadotropic stimulation during both the follicular
      and the luteal phases, how can the responses of the follicle and the corpus
      luteum to their respective trophic hormones differ so dramatically? The actions
      of FSH and LH on the ovary are summarized and a mechanistic hypothesis is
      provided as to how ovarian cyclicity (initiation of follicular development,
      selection of a single preovulatory follicle, corpus luteum function, corpus
      luteum regression, and corpus luteum rescue during early pregnancy) could be
      controlled by a single intracellular messenger: cAMP.

PMID- 11223367
TI  - Insulin-like growth factor family in Graafian follicle development and function.
AB  - The insulin-like growth factor (IGF) family plays an important role in follicle
      development, dominant follicle growth and steroidogenesis, and follicular
      atresia. Insulin-like growth factor (IGF)-II is the primary IGF in human ovary,
      acting as a mediator of gonadotropin action. IGF-II stimulates granulosa
      steroidogenesis, and its actions, along with those of follicle-stimulating
      hormone (FSH), are inhibited by IGF binding protein (IGFBP)-4. At the time of
      follicle selection, in the estrogen-dominant follicle, granulosa IGF-II synthesis
      increases dramatically. Simultaneously, in the selected follicle, IGFBP-4, an
      inhibitor of IGF-II action and abundant within androgen-dominant follicles, is
      proteolyzed by a specific IGFBP-4 protease, resulting in decreased affinity of
      IGFBP-4 for IGF-II. The IGFBP-4 protease has recently been identified in human
      ovary as pregnancy-associated plasma protein-A (PAPP-A). In the Graafian
      follicle, IGF-II bioavailability is increased to act as a mediator of FSH action,
      by increased synthesis of this peptide and concomitant decrease in an inhibitor
      of its actions by proteolysis of IGFBP-4.

PMID- 11223369
TI  - The X chromosome and the ovary.
AB  - X chromosome abnormalities are the leading identifiable cause of premature
      ovarian failure (POF). POF-related abnormalities range from the complete absence
      of one X chromosome to assorted deletions and translocations to mutations in
      specific genes. The diversity of X chromosome abnormalities associated with POF
      indicates that the disorder is genetically heterogeneous. Potential molecular
      mechanisms include both dominant and recessive mutations in X-linked genes as
      well as nonspecific chromosome effects that impair meiosis. A list of candidate X
      linked POF genes is emerging from molecular studies of X chromosome
      abnormalities, data from the Human Genome Project and related functional genomics
      projects, and the results of gene targeting experiments in mice. Mutational
      analysis of candidate genes in a large number of women with idiopathic POF is
      needed to determine which of these genes contribute to the cause of this
      disorder.

PMID- 11223368
TI  - Transgenic models of ovarian failure.
AB  - Reproductive development and function are a complex process requiring the
      coordinate interactions of multiple extragonadal and intragonadal factors.
      Peptide hormones from the hypothalamus (eg, gonadotropin releasing hormone) and
      the pituitary (eg, follicle stimulating hormone, luteinizing hormone, oxytocin)
      as well as growth factors and steroids from the gonads (eg, inhibins, growth
      differentiation factor-9, progesterone, estradiol, testosterone) play key
      functions in regulating specific aspects of reproduction. Our laboratory used
      spontaneous mutant mice and transgenic mouse models to address the essential
      roles of some of these factors in the propagation of the mammalian species. This
      review summarizes some of our initial studies to understand this process.

PMID- 11223370
TI  - Ovarian gene database.
AB  - OBJECTIVE: The entire human genome will be sequenced in September 2000. Facing
      the exponential increase of data in the GenBank at the National Center for
      Biotechnology Information, reproductive biologists are being bombarded with
      massive amounts of information on diverse genes. It is becoming increasingly
      difficult for individual investigators to sort out the diverse genetic and
      physiologic information on the localization and function of different genes in
      the ovary. To alleviate the present situation, we have taken advantage of the
      accessibility of the Internet and initiated a project that serves the entire
      ovarian research community. RESULTS AND DISCUSSION: The Ovarian Kaleidoscope
      database provides information regarding biologic function, expression pattern,
      and regulation of genes that are expressed in the ovary. In addition, it serves
      as a gateway to other online information resources relevant to ovarian research
      by offering results from original papers and data about nucleotide and amino acid
      sequences, and human and murine mutation phenotypes. All references are linked by
      hypertext to PubMed and additional links to sequence databases are also included.
      This information is accessible online and searchable not only by gene name but
      also by criteria such as the cellular and ovarian function of the gene product,
      the expression of genes in different ovarian cell types, or their association
      with specific ovarian phenotypes.

PMID- 11223371
TI  - Oxidative stress and the ovary.
AB  - Superoxide (O(2)(-)), hydrogen peroxide (H(2)O(2)), and lipid peroxides are
      generated in luteal tissue during natural and prostaglandin-induced regression in
      the rat, and this response is associated with reversible depletion of ascorbic
      acid. Reactive oxygen species immediately uncouple the luteinizing hormone
      receptor from adenylate cyclase and inhibit steroidogenesis by interrupting
      transmitochondrial cholesterol transport. The cellular origin of oxygen radicals
      in regressing corpora lutea is predominantly from resident and infiltrated
      leukocytes, notably neutrophils. Reactive oxygen species are also produced within
      the follicle at ovulation and, like the corpus luteum, leukocytes are the major
      source of these products. Antioxidants block the resumption of meiosis, whereas
      the generation of reactive oxygen induces oocyte maturation in the follicle.
      Although oxygen radicals may serve important physiologic roles within the ovary,
      the cyclic production of these damaging agents over years may lead to an
      increased cumulative risk of ovarian pathology that would probably be exacerbated
      under conditions of reduced antioxidant status.

PMID- 11223372
TI  - The ovary as an immune target.
AB  - The ovary does not have a distinct morphologic barrier between the immune system
      and the developing gametes. This is in contrast to the testis in which the
      junctional complexes between the Sertoli cells form the blood-testis barrier.
      Whereas there are numerous factors, including genetic ones, associated with
      ovarian dysfunction, the immune factors have frequently been implicated in
      ovarian dysfunction. Much of our knowledge used to evaluate the immune system of
      the ovary has come from studies on the expression of the zona pellucida (ZP)
      proteins during ovarian development. Initial studies by Dunbar and colleagues
      demonstrated that immunization of rabbits with porcine ZP proteins (but not
      rabbit ZP proteins) would result in the generation of antibodies that inhibit
      sperm binding to the ZP and interfere with normal ovarian follicular development.
      In contrast to the rabbit and primate models, immunization of mice or rats with
      porcine ZP proteins does not have an effect on fertility or ovarian function
      although immunization of certain strains of mice with mouse ZP peptides and
      immune activator systems has been shown to result in ovarian pathology. Whereas
      immune inflammatory reactions have been observed in the mouse models, no such
      immune reactions have been observed in rabbit, guinea pig, or nonhuman primate
      models. Subsequent observations in nonhuman primates have shown that immunization
      of primates with ZP proteins expressed from cDNAs coding for the mouse and rabbit
      ZP2 (the mouse homologue has 60% amino acid identity with human ZP2) or the mouse
      ZP3 (the mouse protein has 67% amino acid identity with human ZP3) causes ovarian
      dysgenesis. In contrast, immunization of primates with recombinant rabbit ZP1
      protein (the mouse homologue has 39% amino acid identity with human ZP1) does not
      affect nonhuman primate ovarian function or follicular development but will
      elicit antibodies that inhibit sperm binding to the primate ZP. These studies
      have collectively provided important information concerning the immunologic
      status of the ovary and demonstrate the species variations in immune responses to
      different ovarian immunogens.

PMID- 11223373
TI  - Autoimmune ovarian disease: mechanism of induction and prevention.
AB  - Research on murine autoimmune ovarian disease (AOD) models suggests that the
      following sequence of events operate in prevention and induction of AOD.
      Potentially pathogenic T cells for oocyte antigens that exist in normal mice are
      kept in check by regulatory CD25(+) T cells. Oocyte-specific pathogenic T cells
      are activated when the regulation is lost, as after day 3 thymectomy, or when T
      cells are stimulated through molecular mimicry. Activated, proinflammatory T
      cells induce interstitial ovarian inflammation without disruption in ovarian
      function. Activated T cells also help B cells that respond to endogenous oocyte
      antigens, to produce oocyte autoantibodies of diversified specificities.
      Autoantibodies, nonpathogenic in themselves, retarget T cell-mediated
      inflammation to ovarian follicles resulting in ovarian atrophy and ovarian
      failure. Future studies should determine the applicability of these findings to
      human ovarian autoimmunity.

PMID- 11223374
TI  - Autoimmune hypogonadism as part of an autoimmune polyglandular syndrome.
AB  - The most compelling case for autoimmune mediated hypogonadism occurs when ovarian
      failure is part of an autoimmune polyglandular syndrome (APS). In patients with
      the rare, recessively inherited type 1 APS (APS-1), characterized by the triad of
      chronic mucocutaneous moniliasis, hypoparathyroidism, and Addison's disease,
      primary amenorrhea (elevated pituitary gonadotropins) or oligomenorrhea and
      infertility are constant features. Ovarian failure is associated with
      autoantibodies to steroid hormone secreting cells in the adrenal cortex, Leydig
      cells of the testes, granulosa/thecal cells of the Graffian follicles, corpus
      luteum, and the syncytiotrophoblast of the placenta. These autoantibodies react
      with 3 P450 enzymes involved with steroidogenesis, namely, 21-hydroxylase
      (adrenal specific), 17 alpha-hydroxylase, and the side chain cleavage enzyme.
      Recently the 14 exon, APS-1 (autoimmune regulator or AIRE) gene has been cloned
      (chr. 21p22.3), and multiple mutants discovered. Parents who are obligatory
      heterozygotes for a single mutant gene lack clinical features of APS-1. They also
      do not develop APS-1 autoantibodies. Thus, hypogonadal patients without features
      of APS-1 are unlikely to have AIRE gene mutations. In the more common APS-2/3,
      characterized by combinations of autoimmune thyroid disease, immune mediated type
      1 diabetes, vitiligo, pernicious anemia, and Addison's disease (type 2, not type
      3), ovarian disease may be seen. In primary hypogonadism outside of the context
      of an APS, these autoantibodies are rare.

PMID- 11223375
TI  - Autoimmune ovarian failure: comparing the mouse model and the human disease.
AB  - The neonatal-thymectomy-induced mouse model of autoimmune oophoritis has two
      important similarities with human autoimmune oophoritis. First, in both cases
      there is some defect in the immune system that permits the development of organ
      specific autoimmunity. Second, in both there is some ovarian target under attack.
      In neither case do we fully understand the nature of the immune defect or the
      ovarian target. Because of its strong analogy with the human disease, murine
      experimental postthymectomy autoimmune oophoritis may provide insight into the
      pathogenesis of autoimmune premature ovarian failure in women. Such studies may
      open new avenues toward the development of specific diagnostic and therapeutic
      methods. The histologic distribution of the ovarian lymphocytic infiltration is
      similar in the mouse and the human, and both mice and women with the disorder
      have reduced natural killer cell activity. Furthermore, susceptibility in both
      mice and women appears to be associated with genes outside the major
      histocompatibility complex. Finally, the mouse disorder is associated with a
      persistent neonatal-like Th2 response that suggests possible similarities with
      autoimmune polyglandular failure type 1 in humans. There is no currently
      available validated serum antibody marker that will confirm a clinical diagnosis
      of autoimmune premature ovarian failure. While investigating this animal model we
      cloned a novel gene that encodes an ooplasm-specific antigen associated with
      autoimmune oophoritis in mice. Based on its role in preimplantation development,
      we have designated this antigen Maternal Antigen That Embryos Require (MATER).
      MATER provides a new determinant with which to investigate the mechanisms of
      autoimmune premature ovarian failure.

PMID- 11223376
TI  - Treatment concepts for premature ovarian failure.
AB  - Treatment concepts for premature ovarian failure concern restoration,
      preservation, and substitution of ovarian function. To date, there is no
      effective treatment to restore ovarian function. Preservation of ovarian function
      using cryopreservation and auto- or xenotransplantation will be possible in the
      near future. Regulation of the dynamics of the oocyte pool through GDF9 or AMH is
      not envisaged in the near future. Developments in estrogen receptor research may
      change treatment concepts in hormone replacement therapy.

PMID- 11223377
TI  - Ovarian rescue/protection from chemotherapeutic agents.
AB  - BACKGROUND: After improved long-term survival in young women with lymphoma and
      leukemia undergoing chemotherapy, preservation of future fertility has been the
      focus of recent interest. The investigational endeavors of ovarian
      cryopreservation await the clinical experience of in vitro maturation of thawed
      primordial follicles, their in vitro fertilization, and embryo transfer. Although
      promising, this experience is not yet available. Moreover, the risk of possible
      reimplantation of malignant stem cells with the thawed cryoperserved ovary has
      been raised after experimental animal observations. Therefore, until these
      innovative endeavors prove successful, and in parallel with them, we attempted to
      minimize the gonadotoxic effect of chemotherapy by the cotreatment with a
      gonadotropin-releasing hormone (GnRH) agonistic analogue to induce a temporary
      prepubertal milieu. Whereas inhibin-B concentrations in serum may reflect the
      ovarian granulosa cell compartment, inhibin-A reflects luteal function.
      Immunoreactive inhibin-A and -B in these patients before, during, and after
      gonadotoxic chemotherapy were measured. METHODS: A prospective clinical protocol
      was undertaken in 44 women with lymphoma, aged 15--40 years, ten with leukemia
      and eight undergoing chemotherapeutic treatments for nonmalignant diseases such
      as systemic lupus erythematosus or other autoimmune diseases. A monthly injection
      of depot D-TRP6-GnRH-a was administered from before the start of chemotherapy
      until its conclusion, up to a maximum of 6 months. A hormonal profile was taken
      before starting the GnRH-a/chemotherapy cotreatment, and monthly thereafter until
      the women resumed spontaneous ovulation. This group was compared with a control
      group of 55 women who had been treated with similar chemotherapy. Inhibin-A and 
      B immunoactivity was measured. RESULTS: Whereas all but one (40-year-old) of the
      surviving patients with GnRH-a/chemotherapy cotreatment group resumed spontaneous
      ovulation and menses within 6 months, fewer than half of the patients in the
      control group (chemotherapy without GnRH-A cotreatment) resumed ovarian function
      and regular cyclic activity (P <.05). The remaining 60% experienced premature
      ovarian failure (POF). Temporary increased follicle-stimulating hormone (FSH)
      concentrations were experienced by almost a third of the patients resuming cyclic
      ovarian function, suggesting a reversible ovarian damage in a larger proportion
      of women than those experiencing POF. Inhibin-A and -B decreased during GnRH
      a/chemotherapy cotreatment but increased to normal levels in patients who resumed
      regular ovarian cyclicity and/or spontaneously conceived, compared with low
      levels in those who developed POF. CONCLUSIONS: If these preliminary data are
      consistent in a larger group of patients, inhibin-A or -B concentrations may
      serve as prognostic factors to predict the resumption of ovarian function, in
      addition to the levels of FSH, luteinizing hormone, and estradiol. GnRH-a
      cotreatment should be considered for every woman of reproductive age who receives
      chemotherapy, in addition to assisted reproductive technology and the
      investigational attempts of ovarian cryopreservation for future in vitro
      maturation.

PMID- 11223378
TI  - Menstrual irregularities and the perimenopause.
AB  - The perimenopause is defined as the phase of women's reproductive life between
      the time when cycles change and become irregular until menopause. Compared with
      younger women, follicle-stimulating hormone is elevated. In ovulatory cycles,
      luteal insufficiency frequently occurs. Estrogen secretion is elevated throughout
      the menstrual cycle during some phases of the perimenopause. Perimenopausal women
      are deficient in the hypothalamic-pituitary estrogen positive feedback mechanism
      on luteinizing hormone (LH) secretion. We challenged young and perimenopausal
      women with earlier follicular-phase estrogen boluses to attempt to induce LH
      surges. Whereas six of eight young women exhibited surges, only one of eight
      perimenopausal women had a surge of LH to estrogen challenge. Thus,
      perimenopausal changes involve mechanisms other than ovarian hypofunction.
      Complex central nervous system mechanistic changes also occur. A better
      understanding of the physiology in control mechanisms should allow for better
      symptom management of the perimenopause.

PMID- 11223379
TI  - Endocrine function of the postmenopausal ovary.
AB  - The ovaries of postmenopausal women are smaller than those of premenopausal women
      and consist primarily of stromal cells. These cells have receptors for, and
      respond to, gonadotropins and secrete testosterone and lesser amounts of other
      androgens and estrogens. The ovaries of some postmenopausal women contain P-450
      aromatase and secrete estradiol. There is little evidence that inhibins A or B
      are secreted by postmenopausal ovaries.

PMID- 11223380
TI  - Induction of 7-ethoxyresorufin-O-deethylase activity by planar chlorinated
      hydrocarbons and polycyclic aromatic hydrocarbons in cell lines from the rainbow
      trout pituitary.
AB  - The induction of 7-ethoxyresorufin-o-deethylase (EROD) activity was examined in
      three rainbow trout pituitary cell lines: RTP-91E, RTP-91F and RTP-2. RTP-91E and
      RTP-91F were developed from the pituitary of a male and have epithelial-like and
      fibroblast-like morphologies, respectively. RTP-2, which was described
      previously, was developed from the pituitary of a female and has an epithelial
      like shape. In all cell lines EROD activity was induced by 2,3,7,8-
      tetrachlorodibenzo-p-dioxin (TCDD). Immunoblotting with the polyclonal antibody,
      anti-trout CYP1A1(277-294)/KLH, confirmed induction of a 58-kDa polypeptide.
      Potential inhibitors of the aryl hydrocarbon receptor, geldanamycin and alpha
      naphthoflavone, inhibited EROD induction by TCDD. Other compounds inducing EROD
      activity were 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PCDD), 2,3,7,8
      tetrachlorodibenzofuran (TCDF), 3,3',4,4',5-pentachlorobiphenyl (PCB 126), and 3
      methylcholanthrene (3MC). When judged by the concentration eliciting 50% of the
      maximal response (EC50), induction was similar in RTP-2 and RTP-91E, and less
      effective in RTP-91F. Regardless of the cell line, the rank order from most to
      least potent inducer on the basis of EC50 value was TCDD> or =PCDD>TCDF>PCB
      126>>3MC. When induction potencies were expressed relative to TCDD, the values
      obtained with the pituitary cell lines were similar to previously published
      values derived with a rainbow trout liver cell line.

PMID- 11223381
TI  - Assessment of tissue-level kidney functions with primary cultures.
AB  - Primary cultures of renal proximal tubule have become important tools for
      examination of the mechanisms and control of transepithelial transport processes.
      The utility of the culture preparations for study of integrated tissue functions
      depends upon their accurate expression of in vivo transport processes.
      Maintenance of differentiation in culture is enhanced by contractible collagen
      substratum. Epithelial monolayer primary cultures of flounder and chicken
      proximal tubule, prepared by enzymatic and mechanical maceration with
      differential centrifugation, exhibit functional properties at the tissue level
      that generally resemble known properties of the freshly isolated or in vivo
      proximal tubule. Transepithelial electrical resistances and potential differences
      are very similar or identical to those of intact tubules. Na+-dependent glucose
      transport, a hallmark of proximal tubule function, has the same properties in
      culture as the tissue in vivo. Similarly, where appropriate comparisons are
      possible, amino acid, uric acid, and organic anion and cation transepithelial
      transport processes are qualitatively very similar in culture and in vivo. These
      two non-mammalian primary proximal tubule culture systems adequately reflect in
      vivo function, and thus provide opportunities for experimental manipulation
      otherwise not available.

PMID- 11223382
TI  - Biological functions of trout pavement-like gill cells in primary culture on
      solid support: pH(i) regulation, cell volume regulation and xenobiotic
      biotransformation.
AB  - This review presents results obtained on rainbow trout gill cells in primary
      culture on solid support. Ultrastructural analysis showed that cultured gill
      cells displayed features of pavement cells in situ. Several biological functions
      have been investigated on these cultured cells. First, it was shown that their
      intracellular pH at rest and after acidosis is regulated by a Na+/H+ exchanger.
      Second, gill cells in primary culture can regulate their volume after a cell
      swelling. Intracellular calcium appears to be involved in this regulation. The
      effects of different xenobiotics on the capacity of gill cells to regulate their
      volume are presented. Third, cultured pavement cells contain biotransformation
      enzymes to metabolize xenobiotics. All these results demonstrate that gill cells
      in primary culture on solid support represent a promising in vitro model for the
      study of pavement cells physiology. In conclusion, applications of this culture
      are discussed and compared with the permeable filter method, together with the
      limitations and prospects of this in vitro model on solid support.

PMID- 11223383
TI  - Effects of environmental dilution on body fluid regulation in the yellow
      stingray, Urolophus jamaicensis.
AB  - Adult yellow stingrays (Urolophus jamaicensis), collected off the southeast
      Florida coast, were maintained in filtered and re-circulated synthetic sea water
      (33 per thousand) for 5-13 days at 30 degrees C. Animals exposed to 82%, 74% and
      66% SW in gradual steps exhibited rapid and significant weight gains followed by
      recovery to pre-dilution levels in 2-6 days. Acclimated animals at each salinity
      [100% (N=12), 82% (7), 74% (4) and 66% SW (3)] were anesthetized (MS222) and bled
      from the caudal vein. In 100% SW, stingray plasma was slightly hypo-osmotic to
      the external medium. Plasma osmolality decreased with stepwise dilutions, but
      became increasingly hyperosmotic to the bathing media. Plasma [Na] and [Cl] each
      decreased by approximately 13%, 23% and 16%, respectively, in 82%, 74% and 66%
      SW. Plasma [urea] decreased by 21%, 25% and 59%, respectively. Changes in plasma
      [K] and [Ca] were minor. Mean corpuscular [Hb] measurements suggest that stingray
      red cells swelled less at each dilution than predicted for a passive erythrocyte
      osmometer. RBC [K] decreased by 12%, 36% and 29%, respectively, in 82%, 74% and
      66% SW. Quantitatively, the other measured electrolytes (Cl, Na and Ca) changed
      by lesser amounts. Results suggest that for mild and moderate dilutions (82% and
      74% SW), yellow stingrays release both ions and urea from intracellular and
      extracellular compartments. With further dilution (66% SW), the elasmobranchs
      retain electrolytes at the expense of urea.

PMID- 11223384
TI  - Neuropathogenic properties of Argas (Persicargas) walkerae larval homogenates.
AB  - Several tick species have been demonstrated, described, or suspected to cause
      paralysis in their host during the repletion process, presumably by impairing
      neurotransmission. The resulting polyneuropathy gradually spreads to the upper
      limbs causing incoordination and ends in respiratory failure. This form of
      paralysis is commonly confused with Guillain-Barre syndrome, botulism and
      myasthenia gravis and although the clinical symptoms of these diseases are
      similar, it is not clear whether the pathogenesis is also the same. During this
      study we investigated the mechanism of paralysis by the tick Argas (Persicargas)
      walkerae by determining the effect of larval homogenates on both potassium
      stimulated (calcium-dependent) and veratridine-stimulated (external calcium
      independent) release of [3H]glycine from crude rat brain synaptosomes. The
      results indicated that larval homogenates inhibited both processes. These
      findings are reconcilable with the results obtained for two other paralysis
      causing tick species, Ixodes holocyclus and Dermacentor andersoni, which were
      indicated to cause paralysis by decreasing the synthesis or release of
      acetylcholine at the neuromuscular junction.

PMID- 11223385
TI  - Cytological effects of platelet-derived growth factor on mitochondrial
      ultrastructure in fibroblasts.
AB  - The goal of this study was to evaluate morphofunctional changes in mitochondrial
      ultrastructure after platelet-derived growth factor application in fibroblasts as
      an indicator of mitochondrial activation in processes like wound healing. NRK-49F
      fibroblasts were synchronized, incubated with PDGF (platelet-derived growth
      factor) and studied by electron microscopy. Volume density (Vv), numerical
      density (Nv) and surface density (Sv) were measured by stereological analysis.
      Application of PDGF on NRK-49F caused an increase in mitochondrial volume density
      by 57% and surface area of cristae per mitochondrion by 65%. The numerical
      density of the mitochondria was decreased in the PDGF-treated cells by 23%, but
      at the same time their mean volume was increased. Furthermore, the mitochondria
      had a complex and highly variable shape both in control and PDGF-treated cells,
      possibly indicating the existence of a mitochondrial reticulum. The results
      demonstrated that biochemically active membrane systems in fibroblast
      mitochondria are enlarged as a direct effect of small doses of platelet-derived
      growth factor and support the concept that this factor and related peptides serve
      as mitogens for connective tissue forming cells. Thus, in mitogenic processes
      like wound healing, the high energy demand of fibroblasts is provided by the
      increase of the inner surface of mitochondria.

PMID- 11223386
TI  - Arachidonic and eicosapentaenoic acids in tissues of the firefly, Photinus
      pyralis (Insecta: Coleoptera).
AB  - We report on the presence of high proportions of arachidonic acid (20:4n-6) and
      eicosapentaenoic acid (20:5n-3) in the tissue lipids of adult fireflies, Photinus
      pyralis. Arachidonic acid typically occurs in very small proportions in
      phospholipids (PLs) of terrestrial insects, ranging from no more than traces to
      less than 1% of PL fatty acids, while 20:5n-3 is often missing entirely from
      insect lipids. Contrarily, 20:4n-6 made up approximately 21% of the PL fatty
      acids prepared from whole males and females, and from heads and thoraces prepared
      from males. Proportions of 20:4n-6 associated with PLs varied among tissues,
      including approximately 8% for male gut epithelia, 13% for testes, and
      approximately 25% for light organs and body fat from males. Substantial
      proportions of 20:5n-3 were also associated with PLs prepared from male firefly
      tissues, including 5% for body fat and 8% for light organs. Because 20:4n-6 and
      20:5n-3 are precursors for biosynthesis of prostaglandins and other eicosanoids,
      we considered the possibility that firefly tissues might produce eicosanoids at
      exceptionally high rates. Preliminary experiments indicated otherwise. Hence,
      fireflies are peculiar among terrestrial insects with respect to maintaining high
      proportions of PL 20:4n-6 and 20:5n-3.

PMID- 11223387
TI  - Natriuretic peptide receptors in the central vasculature of the toad, Bufo
      marinus.
AB  - Natriuretic peptide receptors in the central vasculature of the toad, Bufo
      marinus, were characterized using autoradiographical, molecular, and
      physiological techniques. Specific 125I-rat ANP binding sites were present in the
      carotid and pulmonary arteries, the lateral aorta, the pre- and post-cava, and
      the jugular vein, and generally occurred in each layer of the blood vessel. The
      125I-rat ANP binding was partially displaced by the specific natriuretic peptide
      receptor C ligand, C-ANF, which indicates the presence of two types of
      natriuretic peptide receptors in the blood vessels. This was confirmed by a RT
      PCR study, which demonstrated that guanylyl cyclase receptor (NPR-GC) and NPR-C
      mRNAs are expressed in arteries and veins. An in vitro guanylyl cyclase assay
      showed that frog ANP stimulated the production of cGMP in arterial membrane
      fractions. Physiological recordings from isolated segments of the carotid and
      pulmonary arteries and the lateral aorta, which had been pre-constricted with
      arginine vasotocin, showed that rat ANP, frog ANP and porcine CNP relaxed the
      vascular smooth muscle with relatively similar potency. Together, the data show
      that the central vasculature contains two types of natriuretic peptide receptors
      (NPR-C and NPR-GC) and that the vasculature is a target for ANP and CNP.

PMID- 11223388
TI  - Intestinal uptake of betaine in vitro and the distribution of methyl groups from
      betaine, choline, and methionine in the body of broiler chicks.
AB  - The efficiency of betaine absorption into small intestinal slices of broiler
      chicks was studied in vitro with 14C-labeled betaine. The relative proportion of
      Na+-coupled betaine uptake, as well as the total uptake capacity was larger in
      the duodenum than in the jejunum. Dietary betaine increased the Na+-coupled
      uptake in the duodenum. In in vivo-experiments, methyl-14C-labeled betaine,
      methionine, or choline was fed to broiler chicks. Betaine appeared in the blood
      more rapidly, and reached a higher total concentration than choline or
      methionine. The data suggest that choline and methionine were associated with
      plasma lipoproteins whereas betaine remained free in the plasma. The label
      distribution in liver, kidney, and intestinal tissues was studied 24 h after
      label ingestion. Most of the label from betaine was found in the aquaeous phase
      in the muscle, while in the liver and jejunum the label from betaine was
      distributed more evenly between the aquaeous, lipid, and protein phases. Label
      from choline accumulated in the lipid fraction, particularly so in the liver,
      whereas label from methionine showed a more variable distribution pattern. The
      distribution results are interpreted in terms of specific roles of betaine,
      choline, and methionine in methyl group metabolism.

PMID- 11223389
TI  - Ionomycin and 2,5'-di(tertbutyl)-1,4,-benzohydroquinone elicit Ca2+-induced Ca2+
      release from intracellular pools in Physarum polycephalum.
AB  - Calcium level in organelles of the slime mold Physarum polycephalum was monitored
      by chlortetracycline, a low-affinity calcium indicator. It was found that 2,5'
      di(tertbutyl)-1,4,-benzohydroquinone (BHQ) at a concentration of 100 microM, but
      not the highly specific inhibitor of sarco-endoplasmic reticulum Ca2+-ATPase
      (SERCA), thapsigargin (1-10 microM), elicited calcium release from the CTC
      stained intracellular calcium pool. Ionomycin also caused a calcium release
      (23.7+/-5.1%), which was less than that induced by BHQ (30.1+/-6.0%). Procaine
      (10 mM), a blocker of ryanodine receptor, completely abolished the responses to
      BHQ and ionomycin. Another blocker, ryanodine (100 microM), only slightly
      diminished the responses to ionomycin and BHQ. Apparently, BHQ and ionomycin
      acting as a Ca2+-ATPase inhibitor and an ionophore, respectively, elicit an
      increase in [Ca2+]i, which in turn triggers a calcium-induced calcium release
      (CICR) via the ryanodine receptor. Caffeine, an activator of ryanodine receptor,
      at a concentration of 25-50 mM produced a Ca2+-release (5.6-16.0%), which was not
      similar in magnitude to CICR. The response to 25 mM caffeine was only moderately
      inhibited by 25 mM procaine, and almost completely abolished by 50 mM procaine
      and 100 microM ryanodine.

PMID- 11223390
TI  - Metabolic evidence of a 'rumen bypass' or a 'ruminal escape' of nutrients in roe
      deer (Capreolus capreolus).
AB  - As short chain fatty acids produced in the forestomach are insufficient to
      satisfy the energy requirements of the concentrate selecting roe deer (Capreolus
      capreolus), it is proposed that these animals may have other mechanisms to avoid
      energy losses due to microbial fermentation. Nutrients bypassing down the
      ventricular groove (rumen bypass) or ruminal escape of unfermented or partially
      fermented nutrients may be two alternatives. As metabolic evidence for incomplete
      fermentation in the forestomach we investigated: (1) the abundance of the sodium
      dependent glucose co-transporter (SGLT1) in the duodenum; (2) enzyme activities
      of maltase, saccharase and alpha-amylase in duodenal and pancreatic tissue; and
      (3) the proportion of essential, polyunsaturated fatty acids in depot fat samples
      from ruminants of different feeding type and--for comparison--from animals with a
      simple stomach. The high abundance of SGLT1, high enzyme activity and the high
      proportion of polyunsaturated fatty acids in the concentrate selecting ruminants
      support the hypothesis of rumen bypass or ruminal escape of nutrients in roe deer
      and reflect differences in nutrient utilization by ruminants that belong to
      different feeding types.

PMID- 11223391
TI  - Hemolymph levels of methyl farnesoate increase in response to osmotic stress in
      the green crab, Carcinus maenas.
AB  - The salinity of estuarine environments can vary widely, exposing resident
      organisms to considerable osmotic stress. The green crab Carcinus maenas is well
      known for its ability to osmoregulate in response to such stress. Therefore, we
      tested the relationship between osmoregulation and hemolymph levels of methyl
      farnesoate (MF), a compound previously shown to rise in response to various types
      of environmental stresses. When crabs were transferred from 100% seawater to
      dilute (hypo-osmotic) seawater, hemolymph osmolality dropped rapidly, reaching an
      acclimation level 48 h after transfer. Hemolymph levels of MF also rose in these
      animals after a delay of 6 h, and reached a maximum level at 48 h. MF levels
      remained elevated as long as the crabs were maintained in dilute seawater, and
      quickly returned to basal levels when the animals were returned to full strength
      seawater. In most (but not all) animals, MF levels were elevated when hemolymph
      osmolality fell below the isosmotic point (approx. 800 mOsm/kg). These data
      suggest that MF may have a role in osmoregulation by this species. In addition,
      the elevation of MF by hypo-osmotic seawater suggests an experimental strategy
      for manipulating MF levels in crustaceans.

PMID- 11223392
TI  - Physiological effects of seawater intake in adult harp seals during phase I of
      fasting.
AB  - Previous studies have shown that harp seals may drink considerable amounts of
      seawater. The current study was undertaken to study the physiological responses
      to bolus administration of seawater. Adult harp seals (Phoca groenlandica) were
      fasted without access to water for 48 h and then given 1000 or 1500 ml of
      seawater by a stomach tube. Changes in urine and plasma parameters were
      thereafter monitored for another 12-20 h. Urine production and urine excretion
      rate of Na+ and Cl- increased soon after administration and reached a maximum 3-4
      h later. Urine osmolality was kept rather stable and high ( approximately 1500
      mOsm x kg(-1)) following seawater administration, due to a drop in urine
      concentration of urea that was proportional to the simultaneous increase in urine
      concentration of NaCl. Plasma osmolality remained at approximately 340 mOsm x kg(
      1), while plasma concentration of urea decreased some 20-25% due to increased
      excretion of urea when seawater was ingested. Despite bolus administrations of
      seawater of up to approximately 2% of body mass, homeostasis was maintained and
      no ill effects observed. It is concluded that the concentrating abilities of the
      kidneys of harp seals are sufficient to prevent net loss of body water following
      seawater ingestion. Seawater ingestion may, moreover, increase urinary osmotic
      space and thus serve as a mechanism to excrete additional urea produced during
      phase I of fasting.

PMID- 11223393
TI  - Changes in free amino acids in the hemolymph of giant freshwater prawn
      Macrobrachium rosenbergii exposed to varying salinities: relationship to
      osmoregulatory ability.
AB  - Changes in free amino acids (FAA) in the hemolymph of the giant freshwater prawn,
      Macrobrachium rosenbergii, were examined in individuals exposed to varying
      salinities for up to 1 week. In freshwater and under conditions of low salinity,
      total FAA concentrations were maintained between approximately 0.85 and 1 mM and
      did not exhibit changes in response to salinity exposure. Under high salinities,
      total FAA concentrations increased dramatically, reaching up to 2.1 mM depending
      on treatment. Examination of individual amino acid concentrations revealed that
      these increases were based on specific changes in glycine, arginine, alanine,
      proline and lysine. Among these, alanine showed the greatest increases, resulting
      in levels six-fold higher under high salinity than in freshwater and under low
      salinity. The other amino acid species showed increases of 2.5-fold compared to
      original values. These five FAAs in freshwater and under low salinity together
      occupied approximately 45% of total FAA contents and under high salinity
      comprised more than 70% of total FAA contents. These results suggest that
      specific hemolymph FAAs are involved in mediating response to salinity exposure
      in freshwater prawns.

PMID- 11223394
TI  - Effects of sinus gland extract on mandibular organ size and methyl farnesoate
      synthesis in the crawfish.
AB  - Eyestalk inhibition of farnesoic acid O-methyl transferase, which mediates the
      final step of methyl farnesoate synthesis in the mandibular organ of the crawfish
      Procambarus clarkii, was evaluated. Eyestalk removal caused a 20-100-fold
      increase in methyl transferase activity 8-12 days following surgery. The surge in
      activity following eyestalk removal in males was approximately 4 days ahead of
      that of the females. This was accompanied by a three-fold increase in mandibular
      organ protein content. Methyl transferase inhibition was accomplished in vitro
      after only a 15-min exposure to sinus gland extract. The inhibition obtained by
      injecting animals in vivo was noticeably attenuated 6 h following injection. The
      contrast of the short-lived inhibition with the growth and prolonged increase
      following eyestalk removal suggests that the eyestalk exerts both chronic and
      acute effects on the mandibular organ.

PMID- 11223395
TI  - Effects of short chain fatty acids on colonic Na+ absorption and enzyme activity.
AB  - Short chain fatty acids (SCFA) stimulate colonic Na+ absorption and inhibit cAMP
      and cGMP-mediated Cl- secretion. It is uncertain whether SCFA have equivalent
      effects on absorption and whether SCFA inhibition of Cl- secretion involves
      effects on mucosal enzymes. Unidirectional Na+ fluxes were measured across
      stripped colonic segments in the Ussing chamber. Enzyme activity was measured in
      cell fractions of scraped colonic mucosa. Mucosal 50 mM acetate, propionate,
      butyrate and poorly metabolized isobutyrate stimulated proximal colon Na+
      absorption equally (300%). Neither 2-bromo-octanoate, an inhibitor of beta
      oxidation, nor carbonic anhydrase inhibition affected this stimulation. All SCFA
      except acetate stimulated distal colon Na+ absorption 200%. Only one SCFA
      affected proximal colon cGMP phosphodiesterase (PDE) (18% inhibition by 50 mM
      butyrate). All SCFA at 50 mM stimulated distal colon cAMP PDE (24-43%) and
      decreased forskolin-stimulated mucosal cAMP content. None of the SCFA affected
      forskolin-stimulated adenylyl cyclase in distal colon or ST(a)-stimulated
      guanylyl cyclase in proximal colon. Na+-K+-ATPase in distal colon was inhibited
      23-51% by the SCFA at 50 mM. We conclude that all SCFA (except acetate in distal
      colon) stimulate colonic Na+ absorption equally, and the mechanism does not
      involve mucosal SCFA metabolism or carbonic anhydrase. SCFA inhibition of cAMP
      mediated secretion may involve SCFA stimulation of PDE and inhibition of Na+-K+
      ATPase.

PMID- 11223396
TI  - Characterization of oxyntic glands isolated from the rat gastric mucosa.
AB  - A simple and reproducible method for isolating oxyntic glands from the rat
      gastric mucosa was developed. The mucosa was incubated with pronase and EGTA, and
      then treated mechanically to release glands that were separated from single cells
      by sedimentation. Parietal cells were identified by immunostaining using a
      monoclonal antibody against H,K-ATPase. The glandular cells appeared
      morphologically intact. By careful control of the conditions of gland isolation,
      long glandular structures comprising hundreds of cells surrounding the lumen were
      obtained. Intraperitoneal injection of Br-deoxyuridine in the rat 1.5 h before
      the isolation procedure resulted in glands with a labeling of cells in their neck
      region. The glands were viable, as demonstrated by their ability to respond to
      various hormones. Histamine dose-dependently stimulated the acid formation which
      was measured as the accumulation of [14C]aminopyrine. At 100 microM histamine the
      accumulation was increased 5-10-fold. At 100 nM, pentagastrin potentiated the
      histamine stimulated accumulation by approximately 40% but pentagastrin alone did
      not stimulate. The oxyntic glands obtained by the present procedure appear useful
      for studies on cell physiology, including regulation of acid secretion, cellular
      interactions, and possibly also differentiation and proliferation mechanisms
      since long glandular fragments that contained the proliferative zone could be
      isolated.

PMID- 11223397
TI  - Comparison of in vitro systems of protein digestion using either mammal or fish
      proteolytic enzymes.
AB  - Hydrolysis of three different proteins by either crude fish digestive extracts or
      purified mammal proteases was assayed using two different in vitro systems. The
      closed system was a modification of the pH-stat method including a previous acid
      digestion. The open system used a digestion cell containing a semi-permeable
      membrane which allowed continuous separation of the final products of hydrolysis
      with a molecular cut-off of 1000 Da. Assays in both systems resulted a similar
      arrangement of the tested proteins in relation to their ability to be hydrolyzed,
      with casein>fish meal> or =soybean meal. With the exception of casein, no
      significant differences were found between results produced by any of the enzyme
      sources using the closed system. In constrast, significantly higher hydrolysis of
      all proteins was produced by mammal enzymes under conditions operating in the
      open system. Differences in the rate of release of amino acids measured in this
      latter system were related both to the type of protein and the origin of the
      enzymes. When using purified mammal enzymes, release of lysine or phenylalanine
      from casein and soybean was high, but low from fishmeal. Isoleucine and valine
      present in fishmeal were preferentially hydrolyzed by commercial enzymes, but
      glycine and proline by fish enzymes.

PMID- 11223398
TI  - Effect of hypergravity on the Ca/Sr composition of developing otoliths of larval
      cichlid fish (Oreochromis mossambicus).
AB  - The amounts of calcium and strontium were measured by inductively coupled plasma
      mass spectrometry (ICP-MS) in saccular and utricular inner ear otoliths (sagittae
      and lapilli, respectively) of developing cichlid fish. These fish had been
      maintained for 22 days at 3-g hypergravity conditions within a centrifuge. During
      this time-span, the animals completed their ontogenetic development from hatch to
      the free-swimming stage. Neither the morphogenetic development nor the timely
      onset and gain of performance of the swimming behaviour was impaired by the
      experimental conditions. Experimental and control animals also did not differ
      concerning their size (total length). ICP-MS revealed that the otoliths contained
      significantly less calcium (in microg/otolith) after hyper-g exposure compared to
      parallelly raised 1-g control specimens (lapilli: 0.74+/-0.21 vs. 1.16+/-0.41;
      sagittae: 2.09+/-0.49 vs. 2.76+/-0.47). The content of strontium (in
      microg/otolith: lapilli: 0.0044+/-0.0023 vs. 0.0022+/-0.0013; sagittae: 0.0094+/
      0.0026 vs. 0.0081+/-0.0016) and, consequently, the Sr/Ca ratio (Sr/Cax100) was
      increased (lapilli: 0.607+/-0.267 vs. 0.201+/-0.12; sagittae: 0.439+/-0.093 vs.
      0.301+/-0.086). Since the calcium content can be taken as a proxy for otolith
      weight, and because parallelly undertaken morphometric investigations revealed
      smaller otoliths (maximum radius and surface area) due to hyper-g exposure, the
      results suggest that the growth of otoliths at hyper-g is slowed down. Since the
      concentration of trace elements incorporated into otoliths is likely based on the
      composition of the respective protein matrix, our findings suggest that the
      protein metabolism is affected by hypergravity.

PMID- 11223399
TI  - Differential influence of butyrate concentration on proximal and distal colonic
      mucosa in rats born germ-free and associated with a strain of Clostridium
      paraputrificum.
AB  - In vivo influence of butyrate in colonic mucosa was studied using a model of
      gnotobiotic rats monoassociated with a Clostridium paraputrificum. Rats were fed
      a diet containing increasing amounts of non-digestible carbohydrates, the
      fermentation of which led to modulated amounts of butyrate in the large
      intestine. In the proximal colon, the increase in the butyrate concentration
      alters crypt depth and the number of mucus-containing cells; the increase in
      butyrate was highly correlated with the number of neutral-mucin-containing cells.
      Conversely, in the distal colon, no relation was found between the increase in
      butyrate concentration and crypt depth or number of mucin-containing cells. In
      both the proximal and distal colon, the mitotic index remained unchanged. In
      conclusion, in vivo production of physiological quantities of butyrate had a
      trophic effect on proximal colonic mucosa, but did not influence the distal
      epithelium.

PMID- 11223400
TI  - Compartmental responses to acute osmotic stress in Leishmania major result in
      rapid loss of Na+ and Cl-.
AB  - The elemental composition of the cytoplasm, electron dense vacuoles, and
      heterochromatin and euchromatin regions of the nucleus of Leishmania major
      promastigotes was measured by electron probe X-ray microanalysis under iso
      osmotic conditions (305 mOsM) and shortly after a sudden increase (to 615 mOsM)
      or decrease (to 153 mOsM) in the osmolality of the buffer in which they were
      suspended. In response to acute hypotonicity a complete loss of Na from the
      electron dense vacuoles and an approximately threefold decrease in the Na
      concentrations in the cytoplasm and the nuclear regions occurred, together with
      an approximately threefold decrease in Cl content in each compartment and a
      smaller (approx. 1.2-fold) decrease in K content. Thus, in addition to the rapid
      change in shape and release of amino acids known to occur in response to acute
      hypo-osmotic stress, a major efflux of Na and Cl, and, to a lesser extent, of K,
      also occurs. In response to acute hypertonicity Na in the acidocalcisomes did not
      change but Na content of the cytoplasm decreased by 33%. A small increase in the
      S content of the cytoplasm and the electron dense vacuolar compartments occurred.
      No changes were detectable in Ca or Zn content in any of the compartments
      examined in response to hypotonicity or hypertonicity.

PMID- 11223401
TI  - The Environmental Mutagen Society and the emergence of genetic toxicology: a
      sociological perspective.

PMID- 11223402
TI  - Mitochondrial genome instability in human cancers.
AB  - Malfunction of mismatch repair (MMR) genes produces nuclear genome instability
      (NGI) and plays an important role in the origin of some hereditary and sporadic
      human cancers. The appearance of non-inherited microsatellite alleles in tumor
      cells (microsatellite instability, MSI) is one of the expressions of NGI. We
      present here data showing mitochondrial genome instability (mtGI) in most of the
      human cancers analyzed so far. The mtDNA markers used were point mutations,
      length-tract instability of mono- or dinucleotide repeats, mono- or dinucleotide
      insertions or deletions, and long deletions. Comparison of normal and tumoral
      tissues from the same individual reveals that mt-mutations may show as
      homoplasmic (all tumor cells have the same variant haplotype) or as heteroplasmic
      (tumor cells are a mosaic of inherited and acquired variant haplotypes). Breast,
      colorectal, gastric and kidney cancers exhibit mtGI with a pattern of mt
      mutations specific for each tumor. No correlation between NGI and mtGI was found
      in breast, colorectal or kidney cancers, while a positive correlation was found
      in gastric cancer. Conversely, germ cell testicular cancers lack mtGI. Damage by
      reactive oxygen species (ROS), slipped-strand mispairing (SSM) and deficient
      repair are the causes explaining the appearance of mtGI. The replication and
      repair of mtDNA are controlled by nuclear genes. So far, there is no clear
      evidence linking MMR gene malfunction with mtGI. Polymerase gamma (POLgamma)
      carries out the mtDNA synthesis. Since this process is error-prone due to a
      deficiency in the proofreading activity of POLgamma, this enzyme has been assumed
      to be involved in the origin of mt-mutations. Somatic cells have hundreds to
      thousands of mtDNA molecules with a very high rate of spontaneous mutations.
      Accordingly, most somatic cells probably have a low frequency of randomly mutated
      mtDNA molecules. Most cancers are of monoclonal origin. Hence, to explain the
      appearance of mtGI in tumors we have to explain why a given variant mt-haplotype
      expands and replaces part of (heteroplasmy) or all (homoplasmy) wild mt
      haplotypes in cancer cells. Selective and/or replicative advantage of some
      mutations combined with a severe bottleneck during the mitochondrial segregation
      accompanying mitosis are the mechanisms probably involved in the origin of mtGI.

PMID- 11223403
TI  - Genotoxicity of streptonigrin: a review.
AB  - Streptonigrin (SN, CAS no. 3930-19-6) is an aminoquinone antitumor antibiotic
      isolated from cultures of Streptomyces flocculus. This compound is a member of a
      group of antitumor agents which possess the aminoquinone moiety and that includes
      also mitomycin C, porfiromycin, actinomycin, rifamycin and geldanamycin. Because
      of the potential use of SN in clinical chemotherapy, the study of its
      genotoxicity has considerable practical significance.SN inhibits the synthesis of
      DNA and RNA, causes DNA strand breaks after reduction with NADH, induces
      unscheduled DNA synthesis and DNA adducts and inhibits topoisomerase II. At the
      chromosome level, this antibiotic causes chromosome damage and increases the
      frequency of sister-chromatid exchanges.SN cleaves DNA in cell-free systems by a
      mechanism that involves complexing with metal ions and autoxidation of the
      quinone moiety to semiquinone in the presence of NADH with production of oxygen
      derived reactive species. Recent evidence strongly suggests that the clastogenic
      action of this compound is partially mediated by free radicals. The present
      review aims at summarizing past and current knowledge concerning the genotoxic
      effects of SN.

PMID- 11223404
TI  - Mutation processes at the protein level: is Lamarck back?
AB  - The experimental evidence accumulated for the last half of the century clearly
      suggests that inherited variation is not restricted to the changes in genomic
      sequences. The prion model, originally based on unusual transmission of certain
      neurodegenerative diseases in mammals, provides a molecular mechanism for the
      template-like reproduction of alternative protein conformations. Recent data
      extend this model to protein-based genetic elements in yeast and other fungi.
      Reproduction and transmission of yeast protein-based genetic elements is
      controlled by the "prion replication" machinery of the cell, composed of the
      protein helpers responsible for the processes of assembly and disassembly of
      protein structures and multiprotein complexes. Among these, the stress-related
      chaperones of Hsp100 and Hsp70 groups play an important role. Alterations of
      levels or activity of these proteins result in "mutator" or "antimutator" affects
      in regard to protein-based genetic elements. "Protein mutagens" have also been
      identified that affect formation and/or propagation of the alternative protein
      conformations. Prion-forming abilities appear to be conserved in evolution,
      despite the divergence of the corresponding amino acid sequences. Moreover, a
      wide variety of proteins of different origins appear to possess the ability to
      form amyloid-like aggregates, that in certain conditions might potentially result
      in prion-like switches. This suggests a possible mechanism for the inheritance of
      acquired traits, postulated in the Lamarckian theory of evolution. The prion
      model also puts in doubt the notion that cloned animals are genetically identical
      to their genome donors, and suggests that genome sequence would not provide a
      complete information about the genetic makeup of an organism.

PMID- 11223405
TI  - Mechanism of guanine-specific DNA damage by oxidative stress and its role in
      carcinogenesis and aging.
AB  - Reactive species generated by chemicals and UV radiation can cause sequence
      specific DNA damage and play important roles in mutagenesis, carcinogenesis and
      aging. We have investigated sequence specificity of oxidative stress-mediated DNA
      damage by using 32P-labeled DNA fragments obtained from the human c-Ha-ras-1 and
      p53 genes. Free hydroxyl radical causes DNA damage with no marked site
      specificity. Reactive nitrogen species, sulfate radicals, nitrogen-centered
      radicals, benzoyloxyl radical and alkoxyl radical show different sequence
      specificity. Benzoyloxyl radical specifically causes damage to the 5'-G in GG
      sequence. UVA radiation also causes DNA damage at this site through electron
      transfer in the presence of certain photosensitizers. The 5'-G in GG sequence is
      easily oxidized because a large part of the highest occupied molecular orbital is
      distributed on this site. On the basis of these findings, the sequence
      specificity of DNA damage is presumably determined by (a) redox potential of
      reactive species; (b) ionization potential of DNA bases; and (c) site-specific
      binding of metal ion to DNA. Here we discuss the mechanisms of sequence-specific
      DNA damage in relation to carcinogenesis and aging.

PMID- 11223406
TI  - DNA mismatch repair and cancer.
AB  - Five human DNA mismatch repair genes have been identified that, when mutated,
      cause susceptibility to hereditary nonpolyposis colorectal cancer (HNPCC).
      Mutational inactivation of both copies of a DNA mismatch repair gene results in a
      profound repair defect and progressive accumulation of mutations throughout the
      genome. Some of the mutations confer selective advantage on the cells, giving
      rise to cancer. Recent discoveries suggest that apart from postreplication
      repair, DNA mismatch repair proteins have several other functions that are highly
      relevant to carcinogenesis. These include DNA damage surveillance, prevention of
      recombination between nonidentical sequences and participation in meiotic
      processes (chromosome pairing). A brief overview of these different features of
      the human DNA mismatch repair system will be provided, with the emphasis in their
      implications in cancer development.

PMID- 11223407
TI  - Method for serum-free culture of late fetal and early postnatal rat brainstem
      neurons.
AB  - Primary culture of postnatal brainstem neurons in defined medium has not been
      described in the literature. Successful primary culture of brainstem neurons is
      typically restricted to embryonic ages E14-E18. This study describes a method for
      culture of late fetal and early postnatal brainstem neurons using a serum-free
      culture medium. The culture system is based on Neurobasal medium supplemented
      with antioxidant-rich B27 (Life Technologies). Neuron survival was optimized by
      replacing glutamine with GlutaMaxI, by matching osmolality with neuronal age, and
      by using Hibernate medium to increase neuron survival during tissue dissociation.
      This paper describes the first reliable method for culturing brainstem neurons
      from late fetal and early postnatal stages of the rat for up to 6 days
      postpartum.

PMID- 11223408
TI  - A one-step quantitative reverse transcription polymerase chain reaction
      procedure.
AB  - Our laboratory has developed a one-step quantitative reverse transcription
      polymerase chain reaction (RT-PCR) procedure in which the reverse transcriptase
      enzyme and Taq DNA polymerase are combined in the one tube and a single, non
      interrupted, thermal cycling program is performed. In the past, RT-PCR has been
      carried out with two separate steps: (1) reverse transcription of RNA to generate
      a cDNA pool and (2) polymerase chain reaction amplification of the cDNA. The two
      step method can affect the accuracy of the procedure as the total number of
      manipulations is greater, thereby allowing a greater chance for pipetting errors.
      Quantitation by our method is achieved in a single reaction by the use of a
      competitive internal standard that is identical in sequence to the target RNA
      except for a deletion of 107 base pairs and uses identical primers and cycling
      conditions. Using this method, we have been able to quantify the amount of
      message of a G protein (G(zalpha)), in small amounts of tissue, such as dorsal
      root ganglia, from embryonic as well as postnatal mice.

PMID- 11223409
TI  - A new technique for simultaneously recording EMG and movements in experimental
      animals.
AB  - In this protocol a new system is presented for recording EMG signals from leg and
      trunk muscles along with video-recording of leg and trunk movements. The system
      comprises a front-end amplifier consisting of a reference amplifier, a
      differential amplifier with a filter combination and an analog to digital
      converter (ADC). A fiber optic transmitter connects the front end amplifier via a
      fiber cable to a receiver board placed in a personal computer (PC). A dedicated
      software programme (POLY) was written to process the physiological signals on the
      PC. The physiological recordings can be synchronized to video-recordings and the
      principles of this technique are given. The system allows to record artifact-free
      physiological signals and also to link activation patterns in muscles with
      kinematic aspects of movements.

PMID- 11223410
TI  - Protocol for using signal peptide differential display and representational
      difference analysis to isolate differentially expressed cDNAs from fetal mouse
      brain.
AB  - Comparing female and male brain structures reveals a variety of sex differences
      in many vertebrates. Some of these differences are thought to be induced during
      the fetal period by the effect of steroid hormones produced in the gonads. Not
      much is known about molecular mechanisms involved in gender-specific development
      of the brain. We have taken a broad approach to isolate sex-specific genes from
      18.5 days post coitum brain (A. Eriksson, C. Wahlestedt and K. Nordqvist. 1999.
      Isolation of sex-specific cDNAs from fetal mouse brain using mRNA differential
      display and representational difference analysis. Mol. Brain Res., 74, 91-97).
      Female and male mouse brains were screened with the signal peptide differential
      display, developed in our laboratory, and with a modified representational
      difference analysis of cDNA. The resulting sex-specific fragments were verified
      by semi-quantitative RT-PCR. Here we describe these methods in detail.

PMID- 11223411
TI  - Whole-mount confocal immunofluorescence of mammalian CNS.
AB  - Bright-field wholemount labeling techniques applied to the mammalian central
      nervous system (CNS) offer advantages over conventional methods based on sections
      since an immediate and three-dimensional view of the stained components is
      provided. It thereby becomes possible to survey and count large number of cells
      and fibers in their natural relationships. The ability of confocal laser scanning
      microscopy to visualize in one focal plane the fluorescence associated with
      multiple markers could be most valuable by the availability of reliable
      wholemount fluorescent techniques. Accordingly, based in our previously published
      bright-field wholemount protocols [Brain Res. Prot. 2 (1998) 165-173], we have
      devised an effective immmunofluorescence wholemount procedure. We show that
      reliable wholemount fluorescent staining can be obtained using isolated complete
      CNS aged up to rat embryonic day 17, with antibodies penetration in the
      millimeter range. Examples are shown of preparations in which colocalization can
      be observed in nerve cells of cytoskeletal and calcium-binding proteins.

PMID- 11223412
TI  - Metabolically active rat brain slices as a model to study the regulation of
      protein phosphorylation in mammalian brain.
AB  - The reversible protein phosphorylation is the most important cellular regulation
      of the biological functions of many proteins. Disregulation of protein
      phosphorylation is involved in pathogeneses of several human diseases. The
      abnormal hyperphosphorylation of microtubule-associated protein tau and its
      aggregation into neurofibrillary tangles in selective neurons is one of the major
      brain pathologies of Alzheimer's disease and several other related
      neurodegenerative diseases. Here we present metabolically competent rat brain
      slices as a model to study the regulation of protein phosphorylation in brain.
      Employing this model we have been able to study the abnormal hyperphosphorylation
      of tau and other microtubule-associated proteins. We have evaluated the activity
      and intactness of the rat brain slices both biochemically and morphologically.
      Selective inhibition of protein phosphatase 2A in these rat brain slices by the
      treatment with okadaic acid induced hyperphosphorylation of tau at many abnormal
      sites seen in Alzheimer's disease brain and the accumulation of
      hyperphosphorylated tau in pyramidal neurons of the cortex and hippocampus. The
      regulation of the phosphorylation of high-molecular-weight microtubule-associated
      protein, MAP1b, was also studied with this model. This model enables studies on
      the regulation of protein phosphorylation not only biochemically, but also
      histochemically and immunocytochemically. Furthermore, unlike cultured cells, the
      neurons in the brain slices reside in the physiological environment of the brain
      consisting of natural extracellular matrix, neuronal connectivity, and neuronal
      glial interactions.

PMID- 11223413
TI  - Measurement of the synthesis, turnover, and assembly of alpha- and beta-erythroid
      and nonerythroid spectrins in cultured rat hippocampal neurons.
AB  - We describe a method that has allowed us to measure the synthesis, turnover and
      assembly of alpha- and beta-erythroid and nonerythroid spectrins in cultured rat
      hippocampal neurons. For these studies, rat hippocampal cultures containing 74.5
      83.0% neurons were established. B-27 (Gibco) supplement has been used to obtain
      an excellent long-term viability (up to 5 weeks) of hippocampal neurons in
      culture. For the synthesis, turnover, and assembly experiments the neurons were
      labeled with [35S]methionine, and chased with 10-fold excess of cold methionine
      for the turnover experiments. The cells were then lysed and immunoprecipitated
      with alpha, beta-erythroid, alpha, and beta-nonerythroid spectrin antibodies.
      Immunoprecipitated [35S]methionine-labeled spectrins of hippocampal neurons grown
      in vitro produced bands in 5% polyacrylamide minigels strong enough to be
      detected by the high sensitivity screens of a phosphorimager to generate graphs
      from which the synthesis or half-lives of alpha, beta-erythroid, alpha, and beta
      nonerythroid spectrins were calculated. This method can be used to study the role
      of calpain, caspase-3, and the ubiquitin-proteasome system on the synthesis and
      turnover of erythroid and nonerythroid spectrins in resting and depolarized rat
      hippocampal neurons in culture.

PMID- 11223414
TI  - Comparative computations of spike synchronization in visual cortex of cats.
AB  - In recent years it has been proposed that synchronous activity between neurons is
      a putative mechanism to bind together various trigger features of an image. Thus
      the measure of synchronization becomes an important issue since it may be an
      electrophysiological sign of visual perception. This paper describes and compares
      six techniques of computing synchronization strength, that is, the central peak
      of a cross-correlogram. Data were obtained in anesthetized cats prepared for
      electrophysiological recordings in a conventional fashion. Results indicate that:
      (1) eye fits are misleading. Visual inspection of cross-correlograms, may be
      interesting if one needs to estimate approximately synchronization strength and
      the presence of oscillations in the cross-correlograms, however it may be
      misleading if one wants to compare different cross-correlograms; (2) regression
      analysis to compare one method against the others yields a relatively poor
      correlation suggesting that methods are not directly comparable; (3) the
      sensitivity of each computational method is unequal. The results may indicate
      that some functional connections are either under- or over-evaluated depending
      upon the strategy employed to measure synchronization.

PMID- 11223415
TI  - Cryoembedding and sectioning of cochleas for immunocytochemistry and in situ
      hybridization.
AB  - Current emphasis on biochemical and molecular aspects of cochlear anatomy
      underscores the necessity for high quality cryostat sections of the inner ear.
      The large volume of fluid space within the cochlea makes cryoembedding and
      sectioning of the organ more problematic than that of other, more homogeneous
      tissues. Our method for cryoembedding of cochleas for immunocytochemistry and in
      situ hybridization uses slow infiltration with increasing concentrations of
      sucrose followed by degassed embedding medium before final orientation and
      freezing. This method permits high quality cryosections to be cut which preserve
      overall structure and cellular resolution.

PMID- 11223416
TI  - Cortical activation in reading assessed by region of interest-based analysis and
      statistical parametric mapping.
AB  - Reanalysis of our positron emission tomography study on the reading of Japanese
      Kanji (morphograms) and Kana (phonograms) with Statistical Parametric Mapping
      (SPM) Version 96 (Cogn. Brain Res. 9 (2000) 111) were described in comparison
      with our previous region of interest (ROI)-based analysis. Some areas were
      activated in one analysis but not in the other, which was due to the
      methodological differences. Furthermore, we conducted cognitive subtraction
      analysis between Kanji and Kana and between Kana words and nonwords and confirmed
      that Kana words activated the lateral occipital gyri more extensively than Kanji
      words.

PMID- 11223417
TI  - Cervical lymph cannulation to investigate the efflux and effects of
      intracerebroventricular cytokine infusions.
AB  - It is well documented that there is communication between the cerebral spinal
      fluid (CSF) and cervical lymphatics. Recently, it has been demonstrated that
      tumor necrosis factor alpha (TNF-alpha) introduced into the CSF appears in the
      cervical lymph. However, the functional significance of this is less clear. Here
      we describe a protocol to quantitate the efflux of TNF-alpha from the CSF into
      cervical lymph. In addition, we describe a methodology to examine the effects of
      an intracerebroventricular (i.c.v.) infusion of TNF-alpha on lymph volume,
      cellularity and cell phenotype. While TNF-alpha was recovered in the cervical
      lymph following infusion of 125-I labeled TNF-alpha, the dosage of TNF-alpha used
      in this study had no effect on cervical lymph flow, cellularity or cell subsets.
      This protocol can be used to study the efflux of i.c.v. injected macromolecules
      and their effects on lymphocytes in cervical lymph and the regional lymph nodes.

PMID- 11223418
TI  - An in situ hybridization protocol to detect rare mRNA expressed in neural tissue
      using biotin-labelled oligonucleotide probes.
AB  - The use of the non-radioactive in situ hybridization protocols has allowed in
      general to obtain a better resolution of different transcripts at histological
      and cytological levels with a shortening of the developmental time. The common
      protocols using digoxigenin and biotin-labelled probes share a considerable
      limitation depending on the amount of the transcripts present in the tissues.
      This problem becomes more evident when oligonucleotide probes are used, because
      of their small size and lower ability to give sufficient signal amplification.
      The protocol reported here allows to localize rare mRNA expressed in a tissue,
      using a combination of two biotin-labelled oligonucleotide probes followed by
      streptavidin-peroxidase and biotinyl tyramide amplification system.

PMID- 11223419
TI  - Visualization of detergent insoluble cyclic AMP-dependent protein kinase RIalpha
      aggregates in the rat brain.
AB  - Regulatory subunits of the cAMP dependent protein kinases are the most abundant
      receptor for cAMP in eukaryotic cells. Four isoforms of regulatory subunits
      (RIalpha and -beta, RIIalpha and -beta) have been distinguished. Distribution of
      the most abundant RII isoforms has been extensively studied in the brain, by
      immunohistochemistry and biochemical fractionation, while the least abundant RI
      isoforms have been neglected. In neurons most regulatory subunits are bound to
      the cytoskeleton. A protocol is presented that allows immunohistochemical and
      biochemical characterization of detergent-insoluble RI isoforms in the brain.

PMID- 11223420
TI  - Mitral annulus calcification--a window to diffuse atherosclerosis of the vascular
      system.
AB  - Mitral annulus calcification (MAC) is a chronic, non-inflammatory, degenerative
      process of the fibrous support structure of the mitral valve. It occurs more
      often in women and the elderly. MAC is associated with known atherosclerotic risk
      factors such as diabetes mellitus, hypertension and hypercholesterolemia. It is
      also known that patient with MAC have higher prevalence of left atrial and left
      ventricular enlargement, hypertrophic cardiomyopathy, atrial fibrillation, aortic
      valve calcification and stenosis, various cardiac conduction defects, bacterial
      endocarditis, cardiovascular events and stroke, though the etiological basis is
      unknown. Pathological studies from the 80s present a theory that MAC is a form of
      atherosclerosis. In order to test this theory we conducted during the last years
      a few clinical studies to examine the association of MAC and known
      atherosclerotic phenomena. We found higher prevalence of aortic atheroma in
      patients with MAC and atheroma thickness. We also found in MAC patients higher
      prevalence of carotid artery stenosis, coronary artery stenosis, peripheral
      artery stenosis and higher levels of beta2-Glycoprotein I antibodies in patients
      with MAC thickness equal or greater than 5 mm. These studies support the theory
      that MAC is a form of atherosclerosis and define a group of patients with higher
      prevalence of atherosclerotic disease in multiple blood vessels. The purpose of
      this review is to summarize the data concerning MAC and atherosclerotic
      processes, emphasizing that MAC in itself may be an atherosclerotic process.

PMID- 11223421
TI  - Enhanced level of n-3 fatty acid in membrane phospholipids induces lipid
      peroxidation in rats fed dietary docosahexaenoic acid oil.
AB  - The effect of dietary docosahexaenoic acid (DHA, 22:6n-3) oil with different
      lipid types on lipid peroxidation was studied in rats. Each group of male Sprague
      Dawley rats was pair fed 15% (w/w) of either DHA-triglycerides (DHA-TG), DHA
      ethyl esters (DHA-EE) or DHA-phospholipids (DHA-PL) for up to 3 weeks. The palm
      oil (supplemented with 20% soybean oil) diet without DHA was fed as the control.
      Dietary DHA oils lowered plasma triglyceride concentrations in rats fed DHA-TG
      (by 30%), DHA-EE (by 45%) and DHA-PL (by 27%), compared to control. The
      incorporation of dietary DHA into plasma and liver phospholipids was more
      pronounced in the DHA-TG and DHA-EE group than in the DHA-PL group. However, DHA
      oil intake negatively influenced lipid peroxidation in both plasma and liver.
      Phospholipid peroxidation in plasma and liver was significantly higher than
      control in rats fed DHA-TG or DHA-EE, but not DHA-PL. These results are
      consistent with increased thiobarbituric acid reactive substances (TBARS) and
      decreased alpha-tocopherol levels in plasma and liver. In addition, liver
      microsomes from rats of each group were exposed to a mixture of chelated iron
      (Fe(3+)/ADP) and NADPH to determine the rate of peroxidative damage. During NADPH
      dependent peroxidation of microsomes, the accumulation of phospholipid
      hydroperoxides, as well as TBARS, were elevated and alpha-tocopherol levels were
      significantly exhausted in DHA-TG and DHA-EE groups. During microsomal lipid
      peroxidation, there was a greater loss of n-3 fatty acids (mainly DHA) than of n
      6 fatty acids, including arachidonic acid (20:4n-6). These results indicate that
      polyunsaturation of n-3 fatty acids is the most important target for lipid
      peroxidation. This suggests that the ingestion of large amounts of DHA oil
      enhances lipid peroxidation in the target membranes where greater amounts of n-3
      fatty acids are incorporated, thereby increasing the peroxidizability and
      possibly accelerating the atherosclerotic process.

PMID- 11223422
TI  - Characterization of peroxynitrite-oxidized low density lipoprotein binding to
      human CD36.
AB  - Peroxynitrite-mediated oxidation may be an important physiological mechanism for
      oxidation of low density lipoprotein (LDL), however, the molecular basis for the
      interaction of peroxynitrite oxidized LDL (OxLDL) with scavenger receptors such
      as CD36, has not been characterized. In this study, we compared the biochemical
      characteristics and receptor binding of LDL that was oxidized using: (1) Cu2+, a
      standard method of oxidizing LDL in vitro; and (2) 3-morpholinosydnonimine (SIN
      1), a source of peroxynitrite. Both methods of oxidation caused an increase in
      electrophoretic migration of LDL, but greater mobility was observed with Cu2+
      OxLDL. In addition, greater fragmentation of apolipoprotein B was observed
      following Cu2+ oxidation than after SIN-1 oxidation. The levels of lipid
      peroxides and thiobarbituric acid reactive substances were similar after 20 h of
      oxidation by both methods, although the time-course was distinct. Cu2+ and SIN-1
      OxLDL bound specifically to the macrophage scavenger receptor CD36 with high
      affinity. Binding of the 20 h SIN-1 treated LDL to CD36 was comparable to a 4 h
      Cu2+ modified LDL. The binding of Cu2+ and SIN-1-OxLDL to CD36 was similar under
      different biochemical conditions and modifications of the receptor, suggesting
      that OxLDL particles, generated by either method, bind to the same domain of
      CD36. The results demonstrate that SIN-1 produced an oxidized LDL particle that
      binds specifically to CD36 and suggests that peroxynitrite OxLDL may represent a
      more physiologically relevant model than Cu2+-OxLDL for studying the interactions
      of OxLDL with cells and lipoprotein receptors in vitro.

PMID- 11223423
TI  - Synthesis of active high mannose-type lipoprotein lipase in human adipose
      tissues.
AB  - Lipoprotein lipase (LPL) activity in the retroperitoneal adipose tissue of a
      patient with Cushing's syndrome and in the subcutaneous adipose tissue of a
      patient with aseptic necrosis of the femoral head was higher than that in the
      corresponding tissues of the control subjects. The amount of [35S]methionine
      incorporated into LPL was also higher in these patients than in control subjects.
      However, the ratio of activity and amount of radioactivity in the LPL of patients
      was identical to that of control subjects, indicating that LPL synthesized in the
      adipose tissues of patients had a normal specific activity. LPL with Mr = 57000
      was composed of two types of subunits: one type was partially endo H-sensitive,
      yielding a product with Mr = 55000, and the other was totally endo H-sensitive,
      yielding a product with Mr = 52000. Both retroperitoneal and subcutaneous adipose
      tissues of control subjects contained nearly equal amounts of partially and
      totally endo H-sensitive subunits. In the retroperitoneal adipose tissue of a
      patient with Cushing's syndrome, 8% of subunits were partially endo H-sensitive
      and 92% were totally endo H-sensitive. In the subcutaneous adipose tissue of a
      patient with aseptic necrosis of the femoral head, 21% of subunits were partially
      endo H-sensitive and 79% were totally endo H-sensitive. The 24-h treatment of
      subcutaneous adipose tissue of a control subject with 1 mM 1-deoxymannojirimycin
      (dMM) caused the synthesis of active, but totally endo H-sensitive, LPL. Thus, in
      human adipose tissue, the processing of one oligosaccharide chain of an LPL
      subunit to a complex type chain in the trans Golgi was not necessary for the
      expression of activity.

PMID- 11223424
TI  - Lipid peroxidation product 4-hydroxy-2-nonenal acts synergistically with
      serotonin in inducing vascular smooth muscle cell proliferation.
AB  - Formation of an atherosclerotic lesion is in part mediated by inflammatory and
      oxidative mechanisms including lipid peroxidation. To characterize the potential
      role of lipid peroxidation products in atherogenesis, we assessed the effect of 4
      hydroxy-2-nonenal (HNE), a component of oxidatively modified lipids on vascular
      smooth muscle cells (VSMCs) proliferation, and its interaction with serotonin (5
      hydroxytryptamine, 5-HT), a known mitogen for VSMCs. Growth-arrested rabbit VSMCs
      were incubated with different concentrations of HNE in the absence or presence of
      5-HT. VSMCs proliferation was examined by increases in [3H]thymidine
      incorporation into DNA and cell number. HNE and 5-HT stimulated DNA synthesis in
      a dose-dependent manner. HNE had a maximal proliferative effect at a
      concentration of 1 microM (143% of the control) and 5-HT at 50 microM (211%).
      When added together, low concentrations of HNE (0.1 microM) and 5-HT (5 microM)
      synergistically induced DNA synthesis (273%). These effects on DNA synthesis were
      paralleled by an increase in cell number. A 5-HT2 receptor antagonist LY 281067
      (10 microg/ml) and pertussis toxin (10 ng/ml) inhibited the mitogenic effect of 5
      HT only. Protein tyrosine kinase inhibitor erbstatin A (10 microM) completely
      inhibited the mitogenic effect of HNE and partially that of 5-HT and the combined
      effect of HNE+5-HT. Protein kinase C inhibitor Ro 31-8220 (0.1 microM) completely
      inhibited mitogenic effects of both HNE and 5-HT, and also the combined effect of
      HNE+5-HT. The synergistic effect of HNE+5-HT on DNA synthesis was completely
      reversed by the combined use of LY 281067 (10 microg/ml) and antioxidants N
      acetylcysteine (400 microM), vitamin C (200 microM), or vitamin E (20 microM).
      Our results suggest that HNE acts synergistically with 5-HT in inducing VSMCs
      proliferation. Combined use of both antiplatelet and antioxidant therapies may be
      useful for the prevention of VSMCs proliferative disorders associated with
      atherosclerosis and restenosis after angioplasty.

PMID- 11223425
TI  - Lysophosphatidylcholine increases the secretion of matrix metalloproteinase 2
      through the activation of NADH/NADPH oxidase in cultured aortic endothelial
      cells.
AB  - Matrix metalloproteinases (MMPs) play a pivotal role in angiogenesis,
      atherogenesis, vascular remodeling after vascular injury, and instability of
      atherosclerotic plaque. The present study was undertaken to investigate the
      effect of lysophosphatidylcholine, a major component of oxidized low density
      lipoprotein (LDL), on the regulation of MMPs in cultured bovine aortic
      endothelial cells (BAECs). Furthermore, we explored the potential role of
      oxidative stress in the regulation of MMP. LPC increased the secretion of
      gelatinolytic activity, as well as, protein of MMP-2 from BAECs. The stimulation
      of BAEC with superoxide increased the production of MMP-2 and it also induced its
      activation. Electron spin resonance (ESR) with 5,5-dimethyl-1-pyrroline-N-oxide
      (DMPO) as spin trap agent demonstrated that lysophosphatidycholine (LPC) induced
      generation of reactive oxygen (ROS) species from BAECs. The inhibition of
      NADH/NADPH oxidase, one of the potential sources of superoxide in endothelial
      cells, attenuated the effect of LPC. Our findings suggest that LPC might activate
      the endothelial NADH/NADPH oxidase to enhance superoxide production, and it
      might, in turn, enhance MMP-2 induction.

PMID- 11223426
TI  - MK-954 (losartan potassium) exerts endothelial protective effects against
      reperfusion injury: evidence of an e-NOS mRNA overexpression after global
      ischemia.
AB  - BACKGROUND: the cardiac Renin-Angiotensin system (RAS) plays an important role in
      the regulation of coronary flow and cardiac function and structure in normal and
      pathological conditions such as ischemia-reperfusion (I/R) injury. The aim of
      this study was to investigate the effects of the Angiotensin II type 1 (AT-1)
      receptor antagonist MK-954 (losartan potassium) on postischemic endothelial
      dysfunction and NOS mRNA expression (inducible nitric oxide synthase, iNOS;
      endothelial nitric oxide synthase, eNOS) in isolated working rat hearts. METHODS:
      isolated working rat hearts were subjected to 15 min global ischemia and 180 min
      reperfusion. MK-954 was added to perfusion buffer (a modified Krebs-Henseleit
      solution) at 1 microM concentration. We assessed functional parameters, creatin
      kinase (CK) release, heart weight changes, microvascular postischemic
      hyperpermeability (FITC-albumin extravasation) and morphological ultrastructural
      alterations. eNOS and iNOS mRNA levels were also detected by the means of
      multiplex RT-PCR technique using glyceraldehyde-3-phosphate dehydrogenase (G3PDH)
      gene as internal control; results were expressed as densitometric ratio. RESULTS:
      in Losartan-treated hearts we observed a significant reduction of postischemic
      contractile dysfunction, CK release and myocardial ultrastructural damage;
      postischemic FITC-albumin extravasation was significantly reduced respect to
      controls. Moreover, 1 microM Losartan produced a significant reduction of
      eNOS/G3PDH respect to untreated hearts submitted to I/R. Regarding iNOS/G3PDH
      ratio, no significant changes were detected in Losartan-treated hearts compared
      with controls. CONCLUSIONS: our study revealed that Losartan treatment before
      ischemia, and during reperfusion, is able to reduce the reperfusion injury of the
      rat heart by reducing mechanical and microcirculatory dysfunction and necrotic
      cell death, ameliorating cardiac ultrastructure and endothelial protection,
      probably inducing eNOS over-expression and reducing post-ischemic
      hyperpermeability of coronary microcirculation.

PMID- 11223427
TI  - Cerivastatin prevents tumor necrosis factor-alpha-induced downregulation of
      endothelial nitric oxide synthase: role of endothelial cytosolic proteins.
AB  - Cardiovascular disease is accompanied by an impaired endothelium-dependent
      vasodilatory response. Loss of endothelial nitric oxide synthase (eNOS)
      expression may contribute to endothelial dysfunction. The aim of the present
      study was to analyze the effect of cerivastatin, a novel HMG CoA reductase
      inhibitor, on tumor necrosis factor-alpha (TNF-alpha)-induced downregulation of
      eNOS protein expression in bovine aortic endothelial cells (BAEC). TNF-alpha (10
      ng/ml)- incubated BAEC showed a reduced expression of eNOS protein and decreased
      eNOS mRNA stabilization. This effect was associated with an increased binding
      activity of BAEC cytosolic proteins to the 3'-untranslated region (3'UTR) of eNOS
      mRNA. Cerivastatin prevented TNF-alpha-induced downregulation of eNOS protein
      expression in a concentration-dependent manner (10(-8) to 10(-5) M). Cerivastatin
      also prevented the binding of the cytosolic proteins to 3'-UTR of eNOS mRNA and
      was associated with eNOS mRNA stabilization. The reduced expression of eNOS
      protein by TNF-alpha was also prevented by coincubation with cycloheximide. In
      addition cycloheximide inhibited the binding activity of the cytosolic proteins
      to 3'-UTR of eNOS mRNA, suggesting the inducible character of the mentioned
      cytosolic proteins. TNF-alpha stimulated the translocation of nuclear factor
      kappaB (NF-kappaB), an effect that was not modified by cerivastatin. Furthermore,
      an inhibitor of NF-kappaB translocation, pyrrolidine dithiocarbamate failed to
      modify both the downregulation of eNOS expression and the increased binding
      activity of the cytosolic proteins to 3'-UTR of eNOS mRNA by TNF-alpha. The
      effect of cerivastatin on eNOS expression and the binding activity of the
      cytosolic proteins were reversed by coincubation with L-mevalonate. In
      conclusion, cerivastatin stabilized eNOS mRNA and upregulated eNOS expression in
      the endothelium, and this was associated with a decreased binding activity of
      cytosolic proteins to 3'-UTR of eNOS mRNA. The effect of cerivastatin on the
      regulation of eNOS expression was independent of NF-kappaB mobilization by TNF
      alpha. These findings suggest that cerivastatin may have beneficial effects on
      the endothelial dysfunction associated with cardiovascular diseases beyond its
      effect on lowering cholesterol.

PMID- 11223428
TI  - Relative sensitivities of plasma lecithin:cholesterol acyltransferase, platelet
      activating factor acetylhydrolase, and paraoxonase to in vitro gas-phase
      cigarette smoke exposure.
AB  - In order to identify potential atherogenic properties of gas-phase cigarette
      smoke, we utilized an in vitro exposure model to determine whether the activities
      of several putative anti-atherogenic enzymes associated with plasma lipoproteins
      were compromised. Exposure of heparinized human plasma to gas-phase cigarette
      smoke produced a dose-dependent reduction in the activity of platelet-activating
      factor acetylhydrolase (PAF-AH). Reductions of nearly 50% in PAF-AH activity were
      observed following exposure to gas-phase smoke from four cigarettes over an 8-h
      period. During this time of exposure, lecithin:cholesterol acyltransferase (LCAT)
      was rendered almost completely inactive (>80%). In contrast, paraoxonase was
      totally unaffected by cigarette smoke. Supplementation of plasma with 1 mM
      reduced glutathione was found to protect both PAF-AH and LCAT from cigarette
      smoke, suggesting that cysteine modifications may have contributed to the
      inhibition of these two enzymes. To evaluate this possibility, we blocked the
      free cysteine residues of these enzymes with the reversible thiol-modifying
      reagent dithiobisnitrobenzoic acid (DTNB). Reversal of the DTNB-cysteine adducts
      following cigarette smoke exposures revealed that LCAT, but not PAF-AH, was
      protected. Moreover, high doses (1.0-10 mM) of acrolein and 4-hydroxynonenal,
      reactive aldehydic species associated with cigarette smoke, completely inhibited
      plasma LCAT activity, whereas PAF-AH was resistant to such exposures. Taken
      together, these results indicate a divergence regarding the underlying mechanism
      of PAF-AH and LCAT inhibition upon exposure to gas-phase cigarette smoke. While
      LCAT was sensitive to exposure to volatile aldehydic products involving, in part,
      cysteine and/or active site modifications, the enzyme PAF-AH exhibited an
      apparent resistance. The latter suggests that the active site of PAF-AH is in a
      microenvironment that lacks free cysteine residues and/or is shielded from
      volatile aldehydic combustion products. Based on these results, we propose that
      cigarette smoke may contribute to atherogenesis by inhibiting the activities of
      plasma PAF-AH and LCAT, but the nature of this inhibition differs for the
      enzymes.

PMID- 11223429
TI  - TGF-beta reduced binding of high-density lipoproteins in murine macrophages and
      macrophage-derived foam cells.
AB  - The expression of macrophage scavenger receptors is regulated by intracellular
      cholesterol levels, as well as by cytokines affecting macrophage effector
      functions. CD36, a member of the type B scavenger receptor family, will bind a
      variety of nonlipoprotein and lipoprotein ligands including high-density
      lipoprotein (HDL). Transforming growth factor-beta (TGF-beta) has been
      demonstrated to modulate macrophage effector functions and is present within
      atherosclerotic lesions. In the present study, the effect of TGF-beta on HDL
      binding by both macrophages and macrophage-derived foam cells was evaluated. TGF
      beta, in a dose-dependent manner, reduced the binding of flurochrome-labeled HDL
      to both macrophages and foam cells. These effects were observed in macrophages
      derived from nonatherosclerotic (BALB/c) as well as from macrophages obtained
      from both apolipoprotein E and low-density lipoprotein receptor knockout mice.
      The decrease in HDL binding was consistent with a significant reduction in CD36
      message levels. The effect of TGF-beta on type B scavenger receptor expression
      was not limited to CD36 as SR-BI message was also downregulated, although the
      effect was more modest. A similar reduction in HDL binding and CD36 message was
      also observed with the immunosuppressive glucocorticoid dexamethasone. These
      results suggest that within the microenvironment of an atherosclerotic lesion,
      TGF-beta and other agents that inhibit macrophage inflammatory responses may
      impact lesion progression through mechanisms that include the modulation of HDL
      foam cell interactions.

PMID- 11223430
TI  - Chymase bound to heparin is resistant to its natural inhibitors and capable of
      proteolyzing high density lipoproteins in aortic intimal fluid.
AB  - Degranulated mast cells are present in the human arterial intima. After
      degranulation of rat serosal mast cells, the secreted neutral serine protease
      chymase remains bound to the heparin proteoglycan matrix of the exocytosed
      granules, forming granule remnants. Addition of granule remnants to human aortic
      intimal fluid results in proteolysis of the apoAI present in the intimal fluid,
      which contains physiological inhibitors of chymase. To study the physiological
      mechanism of this protection of granule remnant-bound chymase against its
      inhibitors, we performed experiments using HDL3 as substrate. Chymase, when bound
      to the heparin proteoglycans of granule remnants, but not when released from
      them, resisted inhibition by the mammalian protease inhibitors alpha1
      antitrypsin, alpha2-antichymotrypsin, alpha2-macroglobulin, and eglin C.
      Importantly, the heparin proteoglycan-bound chymase, but not unbound chymase,
      degraded its inhibitor (alpha1-antitrypsin) in the presence of its substrate
      (HDL3). Finally, binding to heparin proteoglycans of a physiological inhibitor of
      chymase (mucus protease inhibitor (MPI)) or of another substrate of chymase (LDL)
      did not inhibit the degradation of HDL3 by granule remnant-bound chymase. This
      study demonstrates that binding of chymase to the heparin proteoglycan chains of
      the exocytosed mast cell granules allows the protease to remain active and
      degrade HDL3 in the presence of its physiological inhibitors and in the presence
      of high concentrations of LDL, such as are found in the interstitial fluid of the
      arterial intima.

PMID- 11223431
TI  - Low-density lipoprotein (LDL) binds to a G-protein coupled receptor in human
      platelets. Evidence that the proaggregatory effect induced by LDL is modulated by
      down-regulation of binding sites and desensitization of its mediated signaling.
AB  - We present evidence of a link between low-density lipoprotein (LDL) receptor
      binding and activation of a platelet G-coupled protein. LDL stimulation induced
      cytosolic [Ca2+]i mobilization, increase in inositol 1,4,5-triphosphate (IP3)
      formation and a rapid cytosol-to-membrane translocation of protein kinase C (PKC)
      enzymatic activity. Pertussis toxin inhibited all the stimulatory effects,
      whereas cholera toxin had no effect. Using ligand-binding assays, we demonstrated
      that exposing platelet LDL receptors to high concentrations of LDL (1.5 g/l)
      caused a rapid down-regulation and desensitization, as shown by the reduction in
      the Bmax, intracellular [Ca2+]i mobilization and IP3 formation to 65, 73 and 63%,
      respectively. The inhibitory effects were reversible and dose and time dependent.
      Furthermore, VLDL (0.2 g/l) and IDL (0.07 g/l) induced similar desensitization
      effects. However, HDL3 (up to 1.5 g/l), chylomicrons (up to 0.5 g/l) and
      cyclohexandione-modified LDL (which does not bind to platelets) had no
      significant effects. Protein kinase C inhibitors (150 nmol/l staurosporine, 100
      micromol/l H-7, and 10 nmol/l bisindolylmaleimide) inhibited desensitization to
      71%, on average. Sequestration blocking agents (0.30 g/l, concanavalin A) had no
      significant effect if phosphorylation was operative. However, there was a
      complete blockade with the concurrent inhibition of both pathways. In contrast,
      cAMP-dependent protein kinase inhibitors (PKI, 1 micromol/l) or beta2-adrenergic
      receptor kinase inhibitors (100 nmol/l, heparin), had no effect. Overall results
      indicate that LDL binds to a pertussis sensitive G-protein coupled receptor and
      that high levels of lipoproteins down-regulate the number of receptors and
      desensitize its mediated response by a mechanism that involves PKC
      phosphorylation and sequestration of binding sites. This new regulatory mechanism
      may have implications for the thrombogenicity in hyperlipidemia and for effects
      of lipid lowering therapy.

PMID- 11223432
TI  - Heme oxygenase-1 attenuates vascular remodeling following balloon injury in rat
      carotid arteries.
AB  - The heme oxygenase-1 (HO-1) system of heme catabolism has been proposed to exert
      protective actions upon the cardiovascular system. This investigation examined
      the influence of HO-1 induction on vascular remodeling following arterial injury.
      Rats were subjected to left carotid artery (LCA) balloon injury following pre
      treatment with either vehicle, the HO-1 inducer hemin (50 mg/kg, SC), or
      concomitant treatment with hemin and the HO-1 inhibitor tin-protoporphyrin IX
      (SnPP-IX; 50 micromol/kg, IP). Animals were injected daily for 14 days post
      injury, after which animals were sacrificed and tissues obtained. Western blot
      analyses revealed vascular HO-1 induction after 2 and 16 days of hemin treatment.
      Positive immunostaining for HO-1 was detected in the endothelial and adventitial
      layers following 48 h of hemin treatment and positive medial staining for HO-1
      after 16 days of hemin treatment. The injured LCA of hemin-treated animals
      demonstrated significantly attenuated neointimal (NI) area (-57%), NI thickness (
      58%), and NI area/medial wall area ratio (-40%) compared to the injured LCA of
      vehicle controls. The cross-sectional medial wall areas of both LCA and uninjured
      RCA were also significantly reduced in the hemin-treated animals. SnPP-IX
      treatment, however, completely restored the NI area, NI thickness, NI area/medial
      wall area ratio, and partially restored the medial wall area towards control
      levels. These results directly implicate HO-1 and the products of heme catabolism
      in attenuating the arterial response to injury and ensuing vascular wall
      remodeling.

PMID- 11223433
TI  - Selective inhibition by probucol of vascular cell adhesion molecule-1 (VCAM-1)
      expression in human vascular endothelial cells.
AB  - An early event in atherogenesis is the adhesion of monocytes to endothelium via
      adhesion molecules, such as VCAM-1 and intracellular adhesion molecule-1 (ICAM
      1). It has been suggested that VCAM-1 plays a very important role in the
      recruitment of monocytes in atherosclerosis. Probucol is a potent inhibitor of
      atherosclerosis in animal models. However, the mechanism of its antiatherogenic
      effect is poorly understood. The aim of our study was to evaluate whether
      probucol can influence the expression of endothelial cell adhesion molecules and
      endothelial adhesiveness. The study was performed on cultured human umbilical
      vein endothelial cells (HUVEC). HUVEC were pretreated with probucol (50 microM)
      at different time periods before stimulation with TNFalpha (100 U ml(-1)) or IL
      1beta (100 U ml(-1)). The protein expression of VCAM-1 and ICAM-1 was measured by
      flow cytometry. VCAM-1 mRNA expression was measured by reverse transcription
      polymerase chain reaction (RT PCR). Probucol time dependently reduced agonist
      induced VCAM-1 ( approximately 45%, 48 h) surface protein and mRNA expression (
      approximately 40%, 48 h) in HUVEC, but not ICAM-1 surface protein expression.
      Decreased VCAM-1 expression was associated with reduction ( approximately 40%) of
      adherence between cytokine-stimulated HUVEC and peripheral blood mononuclear
      leukocytes (PBMC). Our results suggest that the antiatherogenic effect of
      probucol may, in part, be due to a downregulation of VCAM-1 expression.

PMID- 11223434
TI  - F 12511, a novel ACAT inhibitor, and atorvastatin regulate endogenous
      hypercholesterolemia in a synergistic manner in New Zealand rabbits fed a casein
      enriched diet.
AB  - F 12511, a novel ACAT inhibitor, lowers plasma cholesterol levels in New Zealand
      rabbits fed a cholesterol-free casein-rich diet. In rabbits endogenous
      hypercholesterolemia pre-established for 8 weeks was used to compare treatments
      with F 12511 and atorvastatin for a further 8-week period, and to determine
      whether both agents act synergistically. F 12511 appears to be 3-4-fold more
      potent than atorvastatin in reducing total plasma cholesterol (active doses
      ranging from 0.16 to 2.5 and from 1.25 to 10 mg/kg per day, respectively) while
      the hypocholesterolemic efficacy of both compounds at 2.5 mg/kg per day amounted
      to 70 and 45%, respectively. A reduction by as much as 75% of esterified
      cholesterol in liver mediated by F 12511 could account for the decrease of plasma
      VLDL, LDL and apo B-100, whereas a reduction of the LDL production rate has been
      described as the main mechanism underlying the atorvastatin effect. F 12511
      modified adrenal cholesterol balance only at the largest dose studied. In a
      further experiment the co-administration of threshold doses of F 12511 and
      atorvastatin (0.63 and 1.25 mg/kg per day, respectively) lowered plasma total
      cholesterol and apo B-100 containing lipoproteins to a greater extent and more
      rapidly than either agent alone. In the liver a decrease by atorvastatin in free
      cholesterol substrate for ACAT may amplify the effect of F 12511 on cholesteryl
      ester content leading to a diminution, in at least an additive manner, of the
      assembly and secretion of atherogenic lipoproteins in New Zealand rabbits which
      have developed an endogenous hypercholesterolemia. Thus, the combination of the
      ACAT inhibitor F 12511 with atorvastatin can represent a better approach than
      either agent alone to regulate lipoprotein metabolism in certain
      pathophysiological situations.

PMID- 11223435
TI  - Effects of simvastatin treatment on sICAM-1 and sE-selectin levels in
      hypercholesterolemic subjects.
AB  - This study was performed to determine whether the levels of soluble intercellular
      adhesion molecule-1 (sICAM-l) and soluble endothelial molecule-1 (sE-selectin)
      were elevated in subjects with hypercholesterolemia who presented with no other
      risk factors or evidence of atherosclerosis. The effects of administration of an
      HMG-CoA reductase inhibitor on the serum levels of these molecules were also
      examined. Forty hypercholesterolemic subjects (HCh) (19 males and 21 females),
      without hypertension or cardiovascular disease, received placebo for 4 weeks. The
      patients were then randomized in two groups; 20 of them (simvastatin group) were
      treated with simvastatin (20 mg/day) and the other 20 (placebo group) continued
      placebo administration. After 12 and 24 weeks of either simvastatin or placebo
      treatment, sICAM-1 and sE-selectin levels were measured. The same parameters were
      measured in 20 control subjects (C) with normal cholesterol levels, matched for
      sex and age. HCh had sICAM-1 basal values higher than C (352.4+/-57.9 ng/ml
      versus 114.9+/-89.6 ng/ml; P<0.001); however, sE-selectin basal values were not
      different in the two groups. No correlation was observed between HCh sICAM-1
      levels and cholesterol levels (total and low-density lipoprotein). Furthermore,
      cholesterol-lowering treatment with simvastatin did not significantly diminish
      sICAM-1 levels. Our findings would support the hypothesis that patients with
      isolated hypercholesterolemia and without clinical atherosclerosis may be silent
      carriers of arterial subendothelial inflammation, expressed as an increase of
      sICAM-1.

PMID- 11223436
TI  - Parental history of myocardial infarction: lipid traits, gene polymorphisms and
      lifestyle.
AB  - To investigate the relationship between parental history of myocardial infarction
      (MI), lipid traits and gene polymorphisms involved in lipid metabolism, we
      examined Dutch men and women, who were selected from a large population-based
      study. Subjects whose father (n=112), mother (n=115) or both parents (n=115)
      suffered from a premature MI presented with significantly higher apolipoprotein B
      (apo B) levels than subjects without a parental history (n=114). Genetic analyses
      revealed that the apo E4 isoform and the D9N mutation of lipoprotein lipase (LPL)
      were more frequent among subjects with a parental history (P< or =0.05). A
      similar trend was found for the LPL N291S mutation. In contrast, the LPL S447X
      mutation and polymorphisms at the cholesteryl ester transfer protein (TaqIB) and
      apo CIII (SstI) loci proved to be noninformative. Body mass index and lifestyle
      could not explain differences in apo B levels between parental history groups. In
      contrast, the apo E polymorphism and the LPL D9N mutation accounted for some, but
      not all, of the higher apo B levels in subjects with a parental history.
      Therefore, other genetic or lifestyle-related factors must be responsible for the
      increased levels of apo B in individuals with a family history of myocardial
      infarction.

PMID- 11223437
TI  - Atherosclerotic enlargement of the human abdominal aorta.
AB  - Aortic aneurysms usually develop in the atherosclerosis prone infrarenal
      abdominal aorta. To assess the role of atherosclerosis in aortic enlargement, we
      studied the relation between plaque formation and aortic size in 30 pressure
      fixed male cadaver aortas (age 40-95 years, mean age 67 years). Morphometric
      analysis of transverse sections of the mid-thoracic and the mid-abdominal aortas
      included measurement of intimal plaque area, lumen area, plaque and media
      thicknesses. The area encompassed by the internal elastic lamina area (IEL area)
      was taken to be an index of aortic size. IEL area increased with age at both the
      thoracic (r=0.77, P<0.01) and abdominal (r=0.54, P<0.01) aortic levels. The aorta
      also enlarged with increasing plaque area at the thoracic (r=0.73, P<0.01) and
      abdominal (r=0.79, P<0.01) levels. Regression analysis of IEL area on age, body
      weight, height and plaque area revealed that the primary predictor of thoracic
      aortic size was age, whereas the primary predictor of abdominal aortic size was
      plaque area. Plaque thickness in the abdominal aorta was greater than in the
      thoracic aorta (P<0.01). Increased plaque area was associated with a significant
      decrease in media thickness in the abdominal aorta (r=-0.75, P<0.01) but not in
      the thoracic aorta. Aortas with relatively enlarged abdominal segments, i.e.
      those with a thoracic to abdominal ratio of <1.2 (n=13), were compared to those
      with a normal ratio (> or =1.2, n=17). Relatively large abdominal aortas had
      twofold greater plaque area (P<0.001), reduced medial thickness (P<0.05), fewer
      medial elastic lamellae (P<0.01) and greater mural tensile stress (P<0.05) than
      relatively normal abdominal aortas. We conclude that plaque formation in the
      infrarenal abdominal aorta in humans is associated with aortic enlargement and
      decreased media thickness. These changes may be predisposing factors for the
      preferential development of subsequent aneurysmal dilation in the abdominal
      aorta.

PMID- 11223438
TI  - Coronary artery disease in patients at low risk--apolipoprotein AI as an
      independent risk factor.
AB  - Many risk factors for coronary artery disease (CAD) have been established by
      large epidemiological studies. However, some patients without the major risk
      factors still develop disease. Preliminary analysis of individuals referred for
      angiography, who had no major risk factors associated with CAD, indicated that
      apolipoprotein-AI (apoAI) was significantly lower in patients with positive
      angiograms. The hypothesis that apoAI was an independent risk factor for CAD in
      low risk populations was put forth. One thousand and seventy-five consecutive
      patients underwent angiography, lipid analysis, and completed a risk factor
      questionnaire. Individuals with total cholesterol<5.2 mmol/l, high density
      lipoprotein (HDL)-cholesterol>0.9 mmol/l, systolic blood pressure<140 mmHg and
      diastolic blood pressure<90 mmHg, no diabetes, and no family history of premature
      CAD in first degree relatives were selected. Fifty-four patients met these
      selection criteria, 29 having positive evidence of CAD and 25 with no evidence of
      disease. Multivariate analysis revealed that, after adjusting for age and gender,
      serum apoAI level was the only variable predictive of CAD. This effect was
      independent of HDL cholesterol level and fractional esterification rate of HDL
      (FER(HDL)). These results point to an important role for apoAI in the atherogenic
      process, particularly in populations with no major CAD risk factors. Decreased
      levels of apoAI or LpAI may initiate atherosclerosis in a highly selected group
      of low risk patients.

PMID- 11223439
TI  - Relationship between serum lipoprotein(a) level and thrombin generation to the
      circadian variation in onset of acute myocardial infarction.
AB  - A high incidence of acute myocardial infarction (AMI) has been reported between
      06:00 and 12:00 h. This may be related to an abnormality in hemostasis. An
      association has been founded between the serum lipid level and coronary
      atherosclerosis, as well as the serum lipid level and a hemostatic abnormality.
      We investigated the association between the time of AMI, the level of serum
      lipid, and of hemostatic factor. Of the 42 subjects evaluated retrospectively, 20
      had experienced an AMI between 06:00 and 12:00 h (group A), while 22 had
      developed an AMI during some other period (group B). All patients received
      emergency coronary angiography, which identified a total occlusion of coronary
      artery in the proximal portion of the left antecedent branch. The serum level of
      several lipid factors and of hemostatic factors were compared between the two
      groups. Characteristics of patients were similar in both groups. The serum levels
      of lipoprotein(a) (Lp(a)) and of thrombin-antithrombin III complex (TAT) were
      higher in group A than in group B, respectively. The level of other factors were
      similar in both groups. Group A showed a significant correlation between the
      level of Lp(a) and TAT, with a tendency (not statistically significant), toward a
      positive correlation between Lp(a) and PAI-1, and a negative correlation between
      Lp(a) and t-PA. In a subgroup that experienced AMI in the early morning, a higher
      level of Lp(a) was associated with an elevation of TAT, a marker for thrombin
      generation, and with the level of fibrinolytic factor. This suggests that Lp(a)
      is closely related to the increase in the early morning incidence of AMI via a
      change in the prothrombotic state.

PMID- 11223440
TI  - Diabetes mellitus abolishes ethnic differences in cardiovascular risk factors:
      lessons from a multi-ethnic population.
AB  - AIMS: To compare cardiovascular risk factors in diabetic subjects of different
      ethnic groups, and between new and known diabetic subjects, in the Singapore
      National Health Survey '92. METHODS: Disproportionate stratified sampling
      followed by systematic sampling were used in 3568 (total) respondents of whom
      2743 were non-diabetics, 179 newly diagnosed diabetics and 150 known diabetics.
      Amongst the diabetics, there were 185 Chinese, 66 Malays and 78 Asian Indians.
      Diagnosis of diabetes mellitus (DM) was based on the 2 h glucose alone, after a
      75 g oral glucose tolerance test. Blood pressure (BP), lipid profile, glucose,
      insulin and anthropometric indices were obtained from all subjects. RESULTS:
      Subjects with diabetes (new and known) exhibited significantly higher
      triglyceride (TG), lower high density lipoprotein cholesterol (HDL-C) and low
      density lipoprotein (LDL)/apolipoprotein B (apo B) ratio (LDL size) compared with
      normoglycaemic subjects. They were more obese (generalised and central) and had
      higher systolic and diastolic BP. There was no difference in lipid risk factors
      between the two groups with diabetes although those with new diabetes were more
      obese whilst those with known diabetes had higher fasting glucose. Amongst
      subjects with diabetes, there were no significant differences between ethnic
      groups in TG, HDL-C, LDL/apo B ratio, or waist to hip ratio (WHR). Female Malays
      with diabetes had higher total cholesterol and were more obese whilst male Asian
      Indians with diabetes had higher fasting insulin. CONCLUSION: Asian Indians had
      lower HDL-C and LDL/apo B ratio than Chinese or Malays amongst normoglycaemic
      subjects. However, these differences between ethnic groups were not seen in
      subjects with DM.

PMID- 11223441
TI  - Endothelial function of the popliteal artery in patients with coronary artery
      disease.
AB  - Coronary artery disease (CAD) is associated more closely with atherosclerosis in
      the popliteal than in the brachial artery. This case-control study aimed at
      clarifying whether endothelial dysfunction of patients with CAD can be detected
      non-invasively in the popliteal artery by means of ischemia-induced flow-mediated
      dilation (FMD) and cold pressor reaction (CPR), and how it compares with the
      brachial artery. We further investigated a new mode of evaluation of the CPR.
      Eleven cases with CAD were compared with 16 matched healthy controls. Popliteal
      and brachial arterial diameter was monitored by ultrasound for 20 min following
      ischemia and cold pressor. For CPR, the difference between maximum and minimum
      diameter was defined as maximum vasomotion. In the popliteal artery, maximum
      vasomotion and FMD were significantly smaller in cases than in controls, the
      difference being more pronounced than in the brachial artery, where only maximum
      vasomotion was significantly smaller. After exclusion of current smokers, only
      the difference in maximum vasomotion of both arteries remained significant. We
      conclude that maximum vasomotion may be more sensitive for detection of
      endothelial dysfunction than FMD. Endothelial dysfunction in patients with CAD is
      more pronounced in the popliteal artery than in the brachial artery.

PMID- 11223442
TI  - Hyperhomocysteinemia and hypercholesterolemia associated with hypothyroidism in
      the third US National Health and Nutrition Examination Survey.
AB  - Hypothyroid (thyroid stimulating hormone (TSH)> or =20 mIU/l; N=32) participants
      in the third National Health and Nutrition Examination Survey, Phase 2 (1991
      1994) were compared with non-hypothyroid subjects (0.5 mIU/l<TSH<20 mIU/l;
      N=6490) to examine the relationship between hypothyroidism and
      hyperhomocysteinemia (serum total homocysteine>12 micromol/l) and
      hypercholesterolemia (serum total cholesterol>6.2 mmol/l). After controlling for
      age, gender, and race ethnicity, the odds ratios (95% confidence interval (CI))
      relating hypothyroidism to hyperhomocysteinemia and high total cholesterol were
      4.9 (1.8-14.0) and 8.0 (2.9-21.9), respectively. Based on 26 hypothyroid and 5811
      non-hypothyroid subjects with triglyceride concentration < or =2.82 mmol/l, the
      odds ratio for the relationship between hypothyroidism and high low-density
      lipoprotein (LDL)-cholesterol (>4.6 mmol/l by the Friedewald equation) was 5.3
      (95% CI, 1.3-20.9). Adding additional terms to the multivariate logistic
      regression model had little effect on the odds ratios relating hypothyroidism to
      high total or LDL-cholesterol, but adding terms for serum creatinine
      concentration >123.8 micromol/l and for red blood cell folate and serum vitamin B
      12 concentrations resulted in an attenuated, but still significant (P<0.05), odds
      ratio relating hypothyroidism to hyperhomocysteinemia (2.5; 95% CI, 1.0-6.1).
      Controlling for cigarette smoking, heart attack/stroke history, body mass index,
      and serum albumin concentration did not affect the odds ratios.
      Hyperhomocysteinemia and hypercholesterolemia could help to explain the increased
      risk for arteriosclerotic coronary artery disease in hypothyroidism.

PMID- 11223443
TI  - Distribution and cardiovascular risk correlates of serum triglycerides in young
      adults from a biracial community: the Bogalusa Heart Study.
AB  - Elevated serum triglyceride level is increasingly being recognized as an
      important indicator of cardiovascular risk. The distribution and correlates of
      serum triglycerides were examined in a biracial (black-white) community-based
      sample of 1342 young adults (30% black) aged 20-37 years. Triglyceride levels
      showed significant race (white>black) and sex (male>female) differences. Black
      females, despite their relatively increased body fatness, had lowest triglyceride
      levels. In terms of conjoint trait of dyslipidemia based on the National
      Cholesterol Education Program cutpoints, 9% of white males displayed high
      triglyceride (> or =200 mg/dl) in combination with low high-density lipoprotein
      (HDL)-cholesterol (<35 mg/dl). In comparison, none of the black females fell into
      this category. Serum triglycerides even at levels between 100 and 150 mg/dl were
      significantly adversely associated with risk variables of insulin resistance
      syndrome such as adiposity and visceral fatness measures, HDL-cholesterol,
      insulin, and systolic blood pressure, especially among whites. Visceral fatness
      as measured by waist circumference (except black males) and insulin were the
      major predictors of triglyceride levels. Overall, triglyceride levels above 150
      mg/dl were associated with increased risk of hypertension (odds ratio (OR)=1.8,
      95% confidence interval (CI)=1.8-3.0), type 2 diabetes (OR=3.1, CI=1.4-6.9),
      parental history of hypertension (OR=1.3, CI=1.0-1.8) and parental history of
      type 2 diabetes (OR=1.7, CI=1.2-2.3). Thus, serum triglyceride levels may be
      valuable in the assessment of cardiovascular risk during young adulthood.

PMID- 11223444
TI  - Levels of expression of Fcgamma receptor IIA (CD32) are decreased on peripheral
      blood monocytes in patients with severe atherosclerosis.
AB  - To obtain information in vivo concerning the role of Fcgamma receptors (FcgammaR)
      in atherosclerosis, we used quantitative flow cytometry to measure the levels of
      expression of FcgammaRI and FcgammaRIIA on peripheral monocytes in patients with
      severe atherosclerosis. Expression of several other markers was also measured. We
      found that differences in the levels of expression of FcgammaRI were not
      statistically significant when compared between patients and control subjects.
      For FcgammaRIIA, levels of expression were decreased in the patient group, a
      difference that was statistically significant. Levels of expression of CD14 and
      CD36 were also significantly decreased in the patient group. The decrease in
      expression of FcgammaRIIA was statistically significant when the effects of
      current cigarette smoking status or medication use, including statins, were taken
      into account. There was also a positive and statistically significant correlation
      between high-density lipoprotein-cholesterol and levels of expression of
      FcgammaRIIA for all subjects. In contrast, decreased levels of expression of CD14
      and CD36 were strongly associated with current smoking status or statin use. In
      summary, levels of expression of FcgammaRIIA on peripheral blood monocytes were
      significantly decreased in patients with clinical atherosclerosis. Additional
      studies are warranted to determine if levels of expression of FcgammaRIIA have
      utility as a phenotypic marker for assessing relative risk of atherosclerotic
      disease.

PMID- 11223445
TI  - Diurnal triglyceride profiles: a novel approach to study triglyceride changes.
AB  - Fasting plasma triglycerides (TG) show a high intra-individual variability, and
      therefore, repeated measurements and alternative methodology are necessary when
      studying TG metabolism. In search for novel approaches to study TG changes, we
      evaluated the feasibility of determining ambulatory capillary TG. In addition,
      well-known characteristics (e.g. gender differences) of TG metabolism in healthy
      subjects were determined. In 18 subjects with a wide range of fasting plasma TG,
      the results of standardised oral fat loading tests (50 g m(-2)) were compared to
      their diurnal capillary TG profiles, measured on 3 different days, six times each
      day in an out-patient clinic setting. The diurnal TG-profile was calculated as
      area under the capillary TG curve (TGc-AUC) and as incremental area (dTGc-AUC).
      Clearance of plasma TG after the acute oral fat load correlated well with the
      diurnal TGc-AUC (r=0.77; P<0.01). In addition, hypertriglyceridemic subjects
      (plasma TG >2.0 mmol l(-1)) had a higher diurnal triglyceridemia (49.83+/-15.37 h
      mmol l(-1)) as well as a higher response of plasma TG to the oral fat load
      (42.10+/-15.37 h mmol l(-1)), than the subjects with normal fasting plasma TG
      (29.83+/-11.75 h mmol l(-1) (P<0.05) and 20.75+/-5.89 h mmol l(-1) (P<0.01),
      respectively). In an observational study, 106 volunteers (54 females and 52
      males) measured capillary triglycerides. Food intake was recorded and fasting
      blood was drawn once at the start of the study. Body composition was assessed by
      anthropometric parameters and body-impedance. Repeated measurements of diurnal
      triglyceridemia tended to be less variable than fasting capillary triglycerides
      (mean coefficients of variation 15.1% (range: 0.60-45.9%) and 24.9% (range: 1.44
      72.7%), respectively; P=0.09) for the whole group and in males (18.6% (0.60
      45.9%) and 24.0% (1.4-58.2%), respectively; P=0.07). The mean diurnal TGc-AUC and
      dTGc-AUC were lower in females (16.50+/-4.85 and 1.82+/-3.46 h mmol l(-1),
      respectively) than in males (23.44+/-6.50 and 6.93+/-4.67 h mmol l(-1); P<0.001
      for each). The total daily energy intake was lower in females (8911+/-1905 kJ)
      than in males (11042+/-2604 kJ, P<0.001) because of a lower intake of all
      nutrients. In females, estrogen status determined significantly the capillary TG
      profiles. Stepwise multiple regression analysis for females and males, with TGc
      AUC as the dependent variable, showed that the best predictors were fasting
      capillary TG, gender, systolic blood pressure and mean daily energy intake,
      explaining 72% of the variation. Incremental triglyceridemia was best described
      by gender, mean daily protein intake and systolic blood pressure, explaining 42%
      of the variation. Diurnal capillary TG profiles may be used to estimate the total
      daily load of potential atherogenic particles to which individuals are subjected
      during the day without the need for metabolic ward studies.

PMID- 11223446
TI  - Serum paraoxonase is reduced in type 1 diabetic patients compared to non
      diabetic, first degree relatives; influence on the ability of HDL to protect LDL
      from oxidation.
AB  - Paraoxonase is a serum enzyme with an anti-oxidant function, protecting low
      density lipoproteins (LDL) from oxidative modifications. Diabetic patients are
      suggested to be at greater risk of oxidative stress, which may contribute to the
      significantly higher incidence of vascular disease in this population. Less
      efficient protection mechanisms may be one feature of the greater susceptibility
      to oxidation in diabetes. In this context, the present study examined the
      hypothesis that serum paraoxonase is reduced in type 1 (insulin-dependent)
      diabetic patients and that the reduction can affect the anti-oxidant capacity of
      HDL. Serum paraoxonase concentrations and activities were compared in type 1
      patients and first degree, non-diabetic relatives with particular attention paid
      to the confounding effects of paraoxonase gene polymorphisms. In addition, the
      ability of HDL-paraoxonase to protect low density lipoproteins from oxidation was
      analysed in an in vitro system. Serum concentrations and enzyme activities of
      paraoxonase were significantly lower in type 1 patients compared to non-diabetic,
      first degree relatives. The differences were independent of promoter and coding
      region polymorphisms, which influence serum concentrations and activities of the
      enzyme. Overall, paraoxonase concentrations were a mean 13.3+/-4.5% lower
      (P<0.02) in type 1 patients. Specific activities did not differ between diabetic
      and non-diabetic groups. The concentration ratios of LDL cholesterol:paraoxonase
      (1.37+/-0.51 vs. 1.18+/-0.37, P=0.003) and apolipoprotein B:paraoxonase (0.84+/
      0.33 vs. 0.71+/-0.40; P=0.012) were significantly higher in diabetic patients,
      consistent with a reduced capacity to protect LDL from oxidation. In vitro
      oxidation studies showed that a significantly higher level of lipid
      hydroperoxides was generated in LDL in the presence of HDL, containing
      paraoxonase levels equivalent to those of type 1 patients, compared to HDL
      containing paraoxonase levels equivalent to those of control subjects (mean
      difference 8.1%, P<0.05). The study demonstrates that serum concentrations of the
      antioxidant enzyme paraoxonase are significantly lower in type 1 (insulin
      dependent) diabetic patients compared to non-diabetic, first-degree relatives,
      independently of known gene polymorphisms. Concentrations are reduced to an
      extent that can affect its anti-oxidant capacity. The results are consistent with
      the contention that modifications to serum paraoxonase in type 1 patients can
      increase risk of lipoprotein oxidation and, consequently, risk of vascular
      disease.

PMID- 11223447
TI  - Asymptomatic leg and carotid atherosclerosis in smokers is related to degree of
      ventilatory capacity: longitudinal and cross-sectional results from 'Men born in
      1914', Sweden.
AB  - Although smoking is associated with cardiovascular disease (CVD), many
      individuals remain healthy after many years of smoking. The population based
      cohort 'Men born in 1914' was used to investigate whether the occurrence of non
      invasively detected atherosclerosis among smokers is associated with lung
      function [(i.e. height-adjusted forced expiratory volume during 1 s (FEV1.0) and
      vital capacity (VC)]. Two hundred and seven smokers without history of CVD were
      examined with spirometry and calf plethysmography at 55 years, and with
      spirometry, ankle-arm blood pressure recordings and ultrasound examinations of
      the carotid arteries at 68 years. Eighty-three men had atherosclerosis defined as
      carotid stenosis >30% or ankle-arm index <0.9. FEV1.0 and VC were both at 55
      years (longitudinally) and at 68 years (cross-sectionally) lower among men with
      atherosclerosis at 68 years (55 years: FEV1.0, 3.2+/-0.6 vs. 3.4+/-0.5 l; P=0.02;
      VC, 4.2+/-0.5 vs. 4.4+/-0.5 l; P=0.02; 68 years: FEV1.0, 2.6+/-0.6 vs. 2.9+/-0.7
      l; P=0.004; VC, 3.8+/-0.6 vs. 4.0+/-0.6; P=0.009, for men with and without
      atherosclerosis). The longitudinal and cross-sectional associations between
      FEV1.0, VC and atherosclerosis remained significant after adjustments for several
      potential confounders (tobacco consumption at 55 and 68 years, hypertension,
      diabetes, alcohol consumption at 68 years, and pulse wave amplitude as a measure
      of degree of atherosclerosis at 55 years). We conclude that the risk of
      developing atherosclerosis is associated with the degree of ventilatory capacity.
      The results suggest that in smokers, reduced lung function is a marker of
      susceptibility for atherosclerosis.

PMID- 11223448
TI  - Simvastatin improves arterial compliance in the lower limb but not in the aorta.
AB  - Several cardiovascular risk factors adversely affect arterial compliance or the
      distensibility of large arteries. The role of raised low-density lipoproteins
      (LDL) cholesterol is uncertain, most studies having shown little effect. We,
      therefore, investigated whether lowering LDL would improve arterial compliance.
      Twenty hypercholesterolemic subjects (LDL cholesterol 4.95+/-1.11 mmol/l) were
      randomized to simvastatin (20 or 40 mg daily) or placebo, each for 4 weeks.
      Arterial function was assessed at the end of the placebo and simvastatin periods,
      systemic arterial compliance (SAC) and pulse wave velocities (PWV) centrally
      (aorto-femoral) and peripherally (femoral-posterior tibial). RESULTS:
      Lipoproteins (LDL) cholesterol was reduced similarly with 20 and 40 mg
      simvastatin (ten subjects each dose) and data were pooled. Lipoproteins (LDL)
      cholesterol fell 39%, plasma triglyceride fell 18% and high-density lipoprotein
      (HDL) cholesterol rose 12%, all significant. Systemic arterial compliance (SAC)
      and central PWV did not change significantly but peripheral PWV showed evidence
      of greater compliance after simvastatin (10.1+/-1.3 vs. 9.4+/-1.3 m/s with
      placebo and simvastatin, P<0.03), distensibility being inversely related to PWV.
      Improvement in PWV was greatest in those with poorest baseline values, r=0.50;
      P<0.02. CONCLUSION: Peripheral PWV was alone improved with LDL lowering probably
      because of the muscularity of that arterial bed; central PWV and SAC (in the
      elastic aorta) were not influenced.

PMID- 11223449
TI  - Preferential reduction of very low density lipoprotein-1 particle number by
      fenofibrate in type IIB hyperlipidemia: consequences for lipid accumulation in
      human monocyte-derived macrophages.
AB  - The combined (mixed) type IIB phenotype is typically associated with premature
      atherosclerosis and characterised by concomitant elevation of plasma levels of
      atherogenic triglyceride-rich lipoproteins, consisting of very low density
      lipoprotein (VLDL)-1 (Sf 60-400), VLDL-2 (Sf 20-60), and intermediate density
      lipoprotein (IDL) (Sf 12-20), as well as small dense LDL. After dietary
      stabilisation, type IIB patients received micronised fenofibrate (267 mg/day) for
      up to 12 months. At baseline (T0), patients (n=11) displayed fasting
      triglyceride, cholesterol and apoB levels of 308+/-13, 350+/-17 and 187+/-9
      mg/dl, respectively. Micronised fenofibrate (M-fenofibrate) induced marked
      reductions in plasma triglyceride (TG) (-61%, P<0.0001), total cholesterol (-32%,
      P=0.0005) and apolipoprotein (apo) B (-33%, P<0.001) at 12 months (T12); similar
      effects were seen after 3 months (T3) of treatment. These changes resulted from
      significant reductions in VLDL-1 (-75%, P=0.00001), VLDL-2 (-46%, P=0.002) and
      LDL (-33%, P<0.0003); IDL concentrations were unchanged. At baseline, VLDL-1
      constituted the major TG-rich lipoprotein (TRL) fraction (50% of total mass), but
      only 25% at T12. These drug effects were accompanied by marked increase in HDL-C
      (+20%, P=0.018). Quantitative changes in triglyceride-rich lipoproteins were
      accompanied by significant qualitative modifications in particle size and
      chemical composition (VLDL-1: TG, -10.7%, P<0.001; FC, +59%, P=0.0002; PL, +19%,
      P=0.033; VLDL-2: FC, +11%, P=0.027; IDL: FC, +14%, P=0.0004; PL, +12%, P=0.002).
      Reduction in the TG content of VLDL-1 was reflected in a shift of particle size
      distribution to smaller diameters (mean 45.4 and 42.3 nm, respectively, at T0 and
      T12). We evaluated the relative atherogenicity of TRL subfractions by determining
      their capacity, when normalised to equal particle numbers (as apoB 100 content),
      to induce lipid accumulation in human monocyte-derived macrophages. Among TRL
      subfractions, VLDL-1 (100 microg apoB/ml) possessed the highest capacity to
      induce macrophage lipid loading (up to sevenfold increase in TG content, P<0.001;
      free cholesterol, up to 1.7-fold; P<0.05). At 100 microg apoB/ml, cellular TG
      loading from VLDL-1 was twofold greater than that for VLDL-2 (P<0.01), and
      fivefold greater than for IDL (P<0.01). Despite drug-induced changes in the
      qualitative properties of TRL subfractions, the activity of VLDL-1, VLDL-2 and
      IDL as ligands which lead to induction of macrophage lipid accumulation, at
      equivalent particle numbers, was not detectably altered. By contrast, the fibrate
      mediated reduction in the number of circulating VLDL-1 and VLDL-2 particles (four
      and twofold, respectively) resulted in marked decrease in cellular lipid loading.
      Considered together, these findings suggest that fenofibrate may act at systemic
      and arterial levels to reduce the cardiovascular risk associated with VLDL
      subfractions in patients with a combined hyperlipidemic (type IIB) phenotype.
      Indeed, we speculate that reductions in circulating levels of VLDL-1 and VLDL-2
      may diminish intimal penetration of these particles and thus their propensity to
      enhance arterial macrophage lipid accumulation and foam cell formation. Finally,
      fenofibrate further attenuated the atherogenic lipid profile in these patients by
      inducing marked reduction in LDL and elevation in cardioprotective HDL.

PMID- 11223450
TI  - Acoustic analysis in the diagnosis of voice disorders in children.
AB  - The main aim of this study was to describe the changes in acoustic analysis in
      diagnosing voice disorders in children. The secondary goal was the attempt at
      differentiation of organic and functional disorders by means of acoustic
      analysis. The study included 112 children in treated due to laryngeal papilloma,
      gastro-esophageal reflux, atopic disease and noduli vocales. The following values
      have been determined: basic frequency F(o), jitter, shimmer, F(o) tremor and the
      harmonics to noise ratio (HNR). The study results confirmed that the HNR value
      was the most sensitive indicator of changes in the voice organ.

PMID- 11223451
TI  - Respiratory obstruction as a sign of brainstem dysfunction in infants with Chiari
      malformations.
AB  - Laryngeal respiratory obstruction associated with Chiari malformations was first
      described in 1932. We studied this type of obstruction in six children with one
      or several disorders pointing to brainstem dysfunction (failure to thrive,
      velopharyngeal incompetence, gastroesophageal reflux, or vagal hypertonia). The
      nature of the laryngeal obstruction was highly variable (vocal cord paralysis,
      paradoxical vocal cord motion, laryngomalacia) as were the frequency and severity
      of associated disorders. Chiari malformations should be routinely sought in a
      child with laryngeal respiratory obstruction occurring at birth or later,
      whatever the endoscopic diagnosis, especially when signs of brainstem dysfunction
      are present. The best tool for diagnosing the Chiari malformation is T1- and T2
      weighted MRI. Signs of brainstem dysfunction must be treated symptomatically,
      before treating Chiari malformations by decompressive surgery. This latter
      approach led to full functional recovery in all five children who underwent the
      procedure. Palliative surgical treatment should be reserved for patients in whom
      this procedure is unsuccessful.

PMID- 11223452
TI  - Corrosive esophagitis in children: a 30-year review.
AB  - Caustic ingestion with resultant corrosive esophagitis in the pediatric
      population comprises a heterogeneous group in terms of offending agent, location
      of burn and the degree of damage. Consequently, the treatment of these injuries
      has also varied over the years and the optimal management remains controversial.
      Another area of concern that is seldom reported in the otolaryngology literature
      is the socioeconomic impact of such injuries both on the child and on the family.
      We report a 30-year retrospective review of aerodigestive tract caustic injuries
      at The Hospital for Sick Children. Eighty patients were identified with an age
      range from 1 month to 16 years. Early and late complications are reviewed
      including 23 patients (29%) that developed medical complications and 16 patients
      (20%) that developed severe esophageal strictures. Five of these children
      required repeat prograde dilatation, while 11 children required gastrostomy and
      stringing with subsequent retrograde dilatation. All the 11 children required
      esophageal replacement surgery. The economic and social consequences to the child
      and family were also noted with particular attention to hospital costs, parental
      absenteeism from work, and the need for job relocation. A partial cost analysis
      using a child with a severe injury is presented as an example. Psychological
      aspects such as attempted murder, jail terms and attempted suicides are also
      documented. We also present an analysis of those children requiring esophageal
      replacement surgery, and examine the possible role of esophageal stents in
      recalcitrant strictures.

PMID- 11223453
TI  - Peritonsillar abscess in children: a 10-year review of diagnosis and management.
AB  - OBJECTIVE: peritonsillar abscess is the most common deep neck infection in adults
      and children. However, pediatric patients with their smaller anatomy and often
      inability to cooperate with exam and treatment, provide a challenge. This study
      reviews the experience over the last 10 years at a children's hospital in the
      diagnosis and treatment of pediatric peritonsillar abscess. METHODS: a
      retrospective chart review of 83 children diagnosed with a peritonsillar abscess
      by the Otolaryngology service over a 10-year period (March 1989-February 1999)
      were reviewed. Presenting signs and symptoms, physical findings, age, season of
      presentation, prior pharyngitis history, and prior treatment was collected from
      the charts. Additionally, diagnostic studies (if any), treatment performed,
      bacteriology, and outcome/complications were noted. RESULTS: due to either an
      inability to cooperate fully for examination and treatment, or because of an
      earlier history of significant recurrent pharyngitis or obstructive tonsillar
      hypertrophy, half of the children required treatment in the operating room.
      Twenty-six out of 83 (31%) underwent a quinsy tonsillectomy. Length of stay was
      relatively short (0.9 days). There were no recurrent PTAs in our series, although
      four children initially treated with incision and drainage required tonsillectomy
      for persistent symptoms or residual abscess. Ten of those not treated with
      tonsillectomy (19%) required interval tonsillectomy for recurrent pharyngitis.
      CONCLUSION: limited by the ability to cooperate with treatment, children often
      require different treatment plans. We offer a treatment algorithm for managing
      children with PTAs that takes into account their age, level of cooperativeness,
      co-morbidities and prior history of pharyngitis, PTA or obstructive sleep
      disorder.

PMID- 11223454
TI  - MR imaging of airway obstruction in infants and children.
AB  - Accurate diagnosis is important in the evaluation of airway disorders of infants
      and children. Today, multiple imaging techniques are available to evaluate the
      pediatric airway. In general, it is best to start with simple and readily
      available examinations, which may provide a diagnosis in most cases, and progress
      to more sophisticated studies such as MR imaging. We performed magnetic resonance
      (MR) imaging of 45 infants and children with symptoms of airway obstruction, 14
      of 45 patient symptoms were related to masses of the airway and 31 of 45 patient
      symptoms were related to vascular compression.

PMID- 11223455
TI  - Evaluation of the use of a questionnaire to detect hearing loss in Kenyan pre
      school children.
AB  - In developing countries, there is a lack of trained personnel and testing
      equipment to facilitate the early detection of hearing impairment in children. A
      questionnaire offers a low cost option and the value of this for detecting
      hearing impairment in pre-school children was determined in several districts in
      Kenya. The questionnaire was completed by either teachers, parents/carers or
      community nurses. The children were subsequently tested using pure tone
      audiometry and visual examination of the ear by ENT Clinical Officers, who were
      not given prior access to the results of the questionnaire. A total of 757 (88%)
      questionnaires were completed. Of the 735 children, who could be tested using
      pure tone audiometry, four were found to have a unilateral hearing impairment and
      one was detected by the questionnaire. A total of 13 children had a bilateral
      hearing impairment >40 dB HL. All were detected using the questionnaire. There
      were eight males and five females with ages ranging from 4.2 to 6.9 years, mean
      age 5.7 years and median age 5.8 years. Eight had a sensorineural hearing
      impairment and two a mixed hearing impairment. Three of the children with a
      sensorineural hearing loss had a family history of hearing impairment. No
      question detected all children with a hearing impairment and some questions were
      more discerning than others. There was 100% sensitivity for the questionnaire
      when a hearing loss of >40 dB was considered, but specificity was lower at 75%.
      Negative predictive value was 100%, but the positive predictive value was low,
      6.75%. It was concluded that a questionnaire of this nature could be usefully
      applied at Primary Health Care level for detecting hearing impairment at the pre
      school stage. There would be need for services available for diagnosis, treatment
      and habilitation before a screening programme was introduced.

PMID- 11223456
TI  - Laser supraglottoplasty for laryngomalacia: are specific anatomical defects more
      influential than associated anomalies on outcome?
AB  - OBJECTIVE: To evaluate different CO2 laser procedures on children with various
      types of laryngomalacia and determine the role of associated anomalies on the
      outcome. DESIGN: Retrospective chart review. SETTING: Academic tertiary referral
      center. PATIENTS: Twenty-three children who underwent laser supraglottoplasty for
      laryngomalacia between 1991 and 1998 at the UC Davis Medical Center.
      INTERVENTIONS: CO2 laser vaporization of redundant supraglottic mucosa of the
      aryepiglottic fold, arytenoid, and the epiglottis, or modification of the latter,
      either individually or in combination, based on the obstructing anatomy. OUTCOME
      MEASURES: Immediate, short term, intermediate and long term relief of respiratory
      symptoms, feeding difficulties, effect of associated anomalies on outcome, effect
      of specific anatomic obstructing site and surgical procedure performed on
      outcome, and the incidence of complications inherent to the procedure. RESULTS:
      Children without associated anomalies invariably did very well, with 78%
      immediately resolving their respiratory symptoms and 100% within a week. Twelve
      of the 14 patients with unfavorable immediate results (P<0.01) and all ten with
      short term unfavorable results (P<0.05) had neurologic or anatomic associated
      anomalies. Seven patients, all with associated anomalies, were considered
      surgical failures (P<0.05). These patients also had a significantly longer
      hospital stay (P<0.01). The presence of associated anomalies was significant
      (P<0.01) in determining surgical treatment of reflux or the need for an NG tube
      in treating feeding problems. The anatomic site of abnormality and the specific
      procedure performed did not affect the outcome. There were no serious
      complications inherent to this procedure. CONCLUSIONS: Laser supraglottoplasty,
      in its different modalities, is a safe and effective treatment for all types of
      laryngomalacia, but children with associated neurologic or anatomic anomalies
      will have a more complicated immediate and short term course, as well as a
      significant incidence of failure. Gastroesophageal reflux is an important
      associated condition that requires investigation in these patients, and in severe
      cases will merit surgical procedures to manage. The high incidence of associated
      neuromuscular anomalies suggests that this component has an important role in the
      etiology of laryngomalacia.

PMID- 11223457
TI  - Bleeding ears: a case of Munchausen syndrome by proxy.
AB  - A case is presented of a child who initially presented with genuine aural
      symptoms and pathology. Over a period of time it became apparent that the
      persistent aural bleeding, which is an uncommon feature of Chronic Suppurative
      Otitis Media, was the result of trauma inflicted by its mother; a case of
      Munchausen syndrome by proxy (MSBP).

PMID- 11223458
TI  - Autosomal dominant familial frontonasal dermoid cysts: a mother and her identical
      twin daughters.
AB  - A dermoid cyst is an ectodermal cyst that contains an epithelial lining as well
      as adnexal structures, and may occur in numerous areas of the body. The nasal
      dermoid accounts for 1% of all dermoid cysts and 3-12% of head and neck dermoid
      cysts. While there have been familial cases reported, a genetic inheritance for
      nasal dermoids has not been suggested. We present the first reported case of a
      mother and her identical twin daughters who were all found to have evidence of
      frontonasal dermoid cysts. Our case and a review of literature seem to implicate
      an autosomal dominant inheritance in certain instances of nasal dermoids.

PMID- 11223459
TI  - Sequential parapharyngeal abscesses.
AB  - Deep neck infections are not unusual in either the pediatric or adult
      populations. Multiple, and recurrent abscesses are found not infrequently,
      especially in immunocompromised and debilitated persons. It is very rare to find
      sequential parapharyngeal abscesses without identifiable etiology in an otherwise
      healthy pediatric patient while receiving appropriate, culture-directed,
      intravenous antibiotics. This could be due to underestimation of the extent of
      the infection by CT scanning. The use of intravenous clindamycin as a first-line
      therapy may not be sufficient if a large phlegmon exists. We describe a case of
      sequential, bilateral parapharyngeal abscesses in a 3-year-old patient.

PMID- 11223461
TI  - Neuronal mechanisms of executive control by the prefrontal cortex.
AB  - Executive function is considered to be a product of the coordinated operation of
      various processes to accomplish a particular goal in a flexible manner. The
      mechanism or system responsible for the coordinated operation of various
      processes is called executive control. Impairments caused by damage to the
      prefrontal cortex are often called dysexecutive syndromes. Therefore, the
      prefrontal cortex is considered to play a significant role in executive control.
      Prefrontal participation to executive control can be partly explained by working
      memory that includes mechanisms for temporary active storage of information and
      processing stored information. For the prefrontal cortex to exert executive
      control, neuronal mechanisms for temporary storage of information and dynamic and
      flexible interactions among them are necessary. In this article, we present the
      presence of dynamic and flexible changes in the strength of functional
      interaction and extensive functional interactions among temporal information
      storage processes in the prefrontal cortex. In addition, recent imaging studies
      show dynamic changes in functional connectivity between the prefrontal cortex and
      other cortical and subcortical structures depending upon the characteristics or
      the temporal context of the task. These observations indicate that the
      examination of dynamic and flexible modulation in neuronal interaction among
      prefrontal neurons as well as between the prefrontal cortex and other cortical
      and subcortical areas is important for explaining how the prefrontal cortex
      exerts executive control.

PMID- 11223462
TI  - Delayed and isoform-specific effect of NMDA exposure on neural cell adhesion
      molecules in hippocampus.
AB  - Brief stimulation of N-methyl-D-aspartate (NMDA) receptors has been shown to
      generate proteolytic fragments from the extracellular domain of neural cell
      adhesion molecules (NCAMs). In the present study, hippocampal slice cultures were
      used to demonstrate that such brief stimulation is followed by a delayed increase
      in the 180-kDa isoform NCAM-180. The slices were exposed to NMDA for 30 s
      followed by rapid quenching with the antagonist AP5. Immunoassays of the
      experimental samples indicated that concentrations of NCAM-180 were elevated
      above matched controls 2-3 h after the NMDA exposure, but not at earlier or later
      time points. This effect was isoform-specific as concentrations of the 140-kDa
      NCAM species were not found to increase. Interestingly, similar selectivity was
      evident with prolonged infusions of NMDA where, in contrast to the effect of
      brief stimulation, NCAM-180 content was reduced to 50% while levels of NCAM-140
      were unchanged. Together with previous findings, the data indicate that the
      synaptic chemistries activated by NMDA differentially regulate NCAM-180 at the
      translation level and by localized activation of proteases.

PMID- 11223463
TI  - Immunohistochemical localization of Ca(2+)/calmodulin-dependent protein kinase
      kinase beta in the rat central nervous system.
AB  - We examined regional and intracellular distribution of Ca(2+)/calmodulin
      dependent protein kinase kinase beta (CaM-KK beta), which activated
      Ca(2+)/calmodulin-dependent protein kinase I and IV (CaM-K I and IV)
      immunohistochemically in the central nervous system of the rat by light and
      electron microscopy. Although most neurons in the brain and spinal cord exhibited
      the immunoreactivity, no labeled neurons were observed in the globus pallidus or
      entopeduncular nucleus, and only a small number of neurons showed weak
      immunoreactivity in the substantia nigra pars reticulata. In general, the
      immunoreactivity was observed both in the cytoplasm and cellular nucleus,
      although the immunoreactivity was not found in the cellular nucleus in some large
      neurons such as in the mesencephalic trigeminal nucleus, lateral vestibular
      nucleus or gigant cellular reticular formation. As to motoneurons of the cranial
      nerve nuclei and the anterior horn of the spinal cord, they revealed the
      immunoreactivity both in the cytoplasm and nucleus. The reaction product appeared
      as fine granules in the cytoplasm and nucleus under light microscopy. Electron
      microscopic observations confirmed that the reaction product was localized mainly
      on the Golgi apparatus or on the nuclear chromatin. Immunolabeling for antibody
      against CaM-KK beta was discussed with the distribution of CaM-K I, IV and
      another CaM-KK, CaM-KK alpha, in the central nervous system.

PMID- 11223464
TI  - Biochemical and morphological analysis on the localization of Rac1 in neurons.
AB  - The acquisition of cell type-specific morphologies is a central feature of
      neuronal differentiation. Many extra- and intracellular signals are known to
      cause the morphological changes of neuronal cells through the reconstruction of
      the microfilaments underneath the cell membrane. The membrane microdomain called
      "raft" has been paid much attention, for this domain contains many signal
      transducing molecules including trimeric G proteins and cytoskeletal proteins.
      The raft domain is recovered in a low-density fraction after the treatment of the
      membrane with the non-ionic detergent such as Triton X-100 and the enrichment of
      cholesterol and sphingolipids is ascribed to be responsible for the detergent
      insolubility. In contrast to the well-known localization of trimeric G proteins
      in raft, the localization of small G proteins in the raft is poorly
      characterized. Since Rho family small G proteins (Rho, Rac, and Cdc42) regulate
      the microfilament system, we studied the localization of Rho family small G
      proteins in the raft of rat brain with western blotting. Specific localization of
      Rac1 was detected in the raft from 10-day-old and 8-week-old rat whole brain, and
      also in the raft prepared from the growth cone and synaptic plasma membrane
      fractions. Rho and Cdc42 were, in contrast, recovered in the Triton soluble
      fraction. Double immunostaining of cultured hippocampal neurons with antibodies
      to Rac1 and MAP-2, or Rac1 and tau, showed punctate distribution of Rac1 in axons
      as well as in dendrites.

PMID- 11223465
TI  - Excitotoxicity induces changes in rat brain gangliosides.
AB  - The patterns of major gangliosides in the rat hippocampi and olfactory bulbs was
      examined in vivo after microinjections of Ibotenic acid and L-BOAA (NMDA and AMPA
      receptor agonists, respectively) which were given under free-movement conditions.
      The excitotoxicity induced by injections of Ibotenic acid promoted transient
      ganglioside changes in olfactory bulbs and permanent changes in hippocampus. Four
      days after injections, the amount of gangliosides in the hippocampus increased
      significantly for GQ1b, GT1b and GD1b and decreased in the olfactory bulb for
      GQ1b, GT1b, GD1b, GD1a and GM1 compared to normal ganglioside levels. The
      alterations of gangliosides were minimal 1 day after injections. After 5 weeks,
      the amounts of GQ1b, GT1b and GD1b dramatically decreased in the hippocampus
      while in the olfactory bulbs gangliosides recovered to normal levels. The results
      obtained with L-BOAA 4 days after injections strengthen the results observed in
      the experiments using Ibotenic acid and corroborate our suggestion that
      gangliosides have an active role in the compensatory mechanism to maintain the
      number of glutamate receptors during the excitotoxicity.

PMID- 11223466
TI  - Isolation and characterization of a new immortal rat astrocyte with a high
      expression of NGF mRNA.
AB  - We have established a new line of immortalized rat astrocytes through
      transfection of plasmid pSV3-neo encoding the large T antigen of simian virus 40
      into normal astrocytes. One of these immortalized astrocytes (ACT-57) with a flat
      and polygonal cell shape, exhibited stable growth in a chemically defined medium
      (modified N-2 medium) as well as in medium containing ordinary serum. ACT-57,
      retained a detectable level of expression of glial fibrillary acidic protein
      (GFAP) and its mRNA, and exhibited a stronger expression of nerve growth factor
      (NGF) mRNA than that of normal rat astrocytes or C6 glioma cells. NGF mRNA was
      significantly up-regulated by phorbol ester (12-O-tetradecanoylphorbol 13
      acetate, TPA) and gamma-amino-n-butyric acid (GABA) but not by hydrocortisone.
      None of stimulants (TPA, dibutyryl cyclic AMP (db-cAMP), hydrocortisone, L
      glutamate, carbacol, GABA, dopamine, or isoproterenol) changed the expression
      level of either brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT
      3). There was a discrete difference between ACT-57 and normal astrocytes in the
      response to GABA and isoproterenol. These findings imply that normal cortical
      astrocytes possess a functional heterogeneity whereas the clonal astrocyte, ACT
      57, does not, indicating that ACT-57 cells may be useful for in vitro studies of
      neuron-astrocyte interactions involving the induction of neurotrophic factors
      such as NGF.

PMID- 11223467
TI  - Age-related changes in the subtypes of voltage-dependent calcium channels in rat
      brain cortical synapses.
AB  - Age-related changes in the relative contribution of voltage-dependent calcium
      channel (VDCC) subtypes to depolarization-induced Ca(2+) influx and in the
      density of VDCC subtypes in cortical synapses were investigated using
      synaptosomes and their membrane preparations from brain cortices of Wistar rats.
      The relative contribution of VDCC subtypes to Ca(2+) influx was determined by
      measuring the inhibition of depolarization-induced Ca(2+) influx with four VDCC
      subtype-specific peptide blockers. In adult rat synaptosomes, L-, N-, P- and Q
      type channels accounted for 24, 32, 27 and 12% of the total Ca(2+) influx,
      respectively. Brain aging significantly reduced the relative contributions of N-
      and P-type channels and increased the contribution of the channels resistant to
      the four blockers used. The densities of VDCC subtypes, determined by binding
      experiments using radiolabeled PN200 -110, omega-conotoxin GVIA and omega
      conotoxin MVIIC, were found to be significantly decreased in aged synaptic plasma
      membranes. On the contrary, the dissociation constants of the blockers were not
      changed except for PN200-110-sensitive L-type channels. These results suggest
      that aging alters the relative contributions of each VDCC subtype to
      depolarization-induced Ca(2+) influx and decreases the number of VDCCs in rat
      brain cortical synapses. These changes in VDCCs may lead to age-related
      hypofunction of synaptic neurotransmission in brain cortices.

PMID- 11223468
TI  - Subnuclear distribution of afferents from the oral, pharyngeal and laryngeal
      regions in the nucleus tractus solitarii of the rat: a study using
      transganglionic transport of cholera toxin.
AB  - The central distributions of afferents from the oral cavity, the pharynx, the
      larynx and the esophagus to the nucleus tractus solitarii (NTS) were examined by
      using transganglionic anterograde transport of the cholera toxin B subunit (CT
      b). Injections of CT-b into the body of the tongue and the hard palate resulted
      in heavy labeling of the lateral subnucleus (l-NTS) of the NTS rostral to the
      area postrema. Injection into the root of the tongue resulted in heavy labeling
      of the l-NTS, the dorsal half of the medial (m-NTS), the intermediate (im-NTS)
      and the interstitial (is-NTS) subnuclei rostral to the area postrema. Injections
      into the soft palate and the pharynx resulted in a similar labeling pattern in
      the is-NTS, im-NTS and m-NTS to that in the case of the root of the tongue, but
      this labeling extended rostrocaudally. Heavy labeling of the medial aspect of the
      l-NTS was found in the case of the soft palate, but the labeling was sparse in
      the case of the pharynx. Moderate labeling was also found in the commissural
      subnucleus (co-NTS). Injection into the larynx resulted in labeling of the is-NTS
      throughout the NTS, and of the rostral half of im-NTS. Injection into the
      esophagus resulted in heavy labeling of the central subnucleus, and moderate
      labeling of the co-NTS and the caudal half of im-NTS. A few but consistent
      anterogradely labeled terminals were found to appose retrogradely labeled small
      neurons in the rostral tip of the dorsal motor nucleus of vagus in the cases of
      injections into the root of the tongue, the soft palate, the pharynx, and the
      larynx. These results have characterized the viscerotopic representation of
      afferent projections from the oral and the cervical visceral organs to the
      subnuclei of the NTS.

PMID- 11223469
TI  - Axon trajectories in local circuits of the primary motor cortex in the macaque
      monkey (Macaca fuscata).
AB  - The intrinsic trajectories and terminal arbors of two axons and one horizontal
      axon collateral within the primary motor cortex (M1) were studied in the macaque
      monkey using injections of biotinylated dextran amine (BDA) into the putative
      primary forelimb motor cortex, and two-dimensional (2-D) reconstruction of the
      individually labeled axons and collateral. (1) A long collateral of the main axon
      from a large pyramidal cell in layer Vb of the putative forelimb area on the
      anterior bank of the central sulcus coursed horizontally anteriorly for 3 mm and
      formed a terminal arbor in layer III of M1. (2) The main axon of a pyramidal cell
      in layer IIIa+b of the putative forelimb area on the precentral gyrus descended
      into the white matter and then entered the anterior bank of the central sulcus to
      form a terminal arbor in layers III and V. (3) The main axon of a pyramidal cell
      in layer IIIc of the putative forelimb area on the precentral gyrus descended and
      bifurcated in the white matter. One branch entered the anterior bank of the
      central sulcus to form a terminal field in layer VI. These results indicate that
      some local axons and horizontal axon collaterals arising from M1 reach their
      single targets within M1 to form single terminal fields.

PMID- 11223471
TI  - Effect of gaze direction on sound localization in rear space.
AB  - The effect of eccentric eye position on the localization of sound in rear space
      was investigated, using a two-alternative forced-choice method in combination
      with a visual fixation task. The azimuthal position of the rear sound was
      perceived as shifted slightly (mean 1.2 degrees ) to the left of the subjects'
      median plane when fixation was 30 degrees to the right, or to the right when
      fixation was 30 degrees to the left. Combined with previous studies on
      localization in frontal space, this finding suggests that eye-position signals
      influence processing of binaural, but not monaural spectral, cues for directional
      hearing.

PMID- 11223470
TI  - Effects of fibronectin cleaved by neuropsin on cell adhesion and migration.
AB  - Neuropsin is a serine protease cloned from the mouse hippocampus. Since neuropsin
      is a secreted protein which effectively cleaves fibronectin, it may affect cell
      adhesion or cell migration by modulating the content and/or chemical
      characteriscs of fibronectin in extracellular matrix (ECM). In adhesion assays,
      alpha5B2 cells expressing integrin alpha5beta1 bound less effectively to
      fibronectin teated with neuropsin than intact fibronectin. In Boyden chamber
      chemotaxis assays, the fibronectin-induced migration of alpha5B2 cells was not
      affected by neuropsin treatment. These findings suggest that neuropsin regulates
      the local microenvironment by modulating the interaction between cells and
      fibronectin in ECM.

PMID- 11223473
TI  - Editorial. Pediatric Oncology.

PMID- 11223474
TI  - Problems in the imaging of three common paediatric solid tumours.
AB  - Modern radiologic techniques have led to a more accurate diagnosis and staging in
      many paediatric malignancies. The optimal imaging of some tumours is not,
      however, well defined and needs to be constantly re-assessed. Similarly with
      evolving clinical treatment protocols, recommended imaging strategies should be
      continually re-evaluated. The significance of some findings on radiologic
      examinations in paediatric oncology patients is disputed. A number of issues
      relating to the imaging of Wilms', neuroblastoma and rhabdomyosarcoma in
      childhood are discussed.

PMID- 11223475
TI  - Imaging in skeletal paediatric oncology.
AB  - The prognosis for the child presenting with a bone sarcoma has improved
      dramatically with the introduction of adjuvent chemotherapy. As a result the
      majority of patients can now expect to undergo limb salvage surgery. The role of
      imaging in the management of the child presenting with a suspected sarcoma is
      presented. This commences with tumour detection, through diagnosis and surgical
      staging, re-staging with assessment of response to chemotherapy and follow-up
      surveillance for the development of local recurrence and/or metastases. The
      importance of the multidisciplinary approach to the management of bone sarcomas
      is emphasised.

PMID- 11223476
TI  - Second malignancies in children: the usual suspects?
AB  - The aim of this article is to provide an up to date review of second malignant
      neoplasms (SMN's) following treatment for childhood cancer, referring to their
      incidence, the role of genetic factors, and how the primary malignancy and
      treatment received influence the type, site and prognosis of SMN's. The role of
      genetic factors will be discussed as far as they impact upon a predisposition to
      later development of SMN's. The primary malignancies that have important
      associations with SMN's will then be discussed, in particular Hodgkin's disease,
      retinoblastoma and acute lymphoblastic leukaemia. The important second
      malignancies will be highlighted, including tumours of the CNS and thyroid,
      osteosarcoma, secondary acute myeloid leukaemia and melanoma. Emphasis will be
      put upon identifying which patients are most likely to suffer from these tumours.
      An important part of the article are case histories. These are provided in
      combination with illustrations as a useful adjunct to the text, with a particular
      emphasis on radiological features, diagnosis and screening. Finally, the
      important but different roles of causal agents, in particular chemotherapy and
      radiotherapy are highlighted.

PMID- 11223477
TI  - Complications of treatment of paediatric malignancies.
AB  - Advances in surgical techniques, radiotherapy and chemotherapy have led to
      improved survival for children with solid tumours and leukaemia. However, the
      treatment has also resulted in increased side effects both in the short and long
      term. This article outlines the complications which may arise as a result of
      treatment under the headings of surgery; chemotherapy; radiotherapy; organ
      specific complications; infection and graft-v-host disease.

PMID- 11223478
TI  - Quiz case. Multiple calcifications of intraluminal meconium enterolithiasis.

PMID- 11223479
TI  - Magnetic resonance imaging in follow-up of treated clubfoot during childhood.
AB  - In this study, we evaluated the short-term results of surgically treated clubfoot
      with magnetic resonance imaging (MRI). T1- and T2-weighted MRI images with 4-mm
      slices in the standard anatomic sagittal, transverse, and coronal planes were
      obtained in seven cases of clubfoot aged 4--11 years (mean 5.6 years old). The
      mean follow-up period was 3.6 years (ranged between 2 and 6 years). Sagittal
      talocalcaneal angle, talar head and neck axis internal rotation, calcaneal axis
      internal rotation, transverse talar neck and head/calcaneus angle and posterior
      calcaneus external rotation were measured. Three cases with dorsal talonavicular
      subluxation and a case of calcaneocuboid luxation were demonstrated by MRI. It
      was concluded that MRI may help to understand results of surgically-treated
      clubfoot by revealing hindfoot articular relationships and many complications.

PMID- 11223480
TI  - Humeral hydatid cyst complicated with extraosseous involvement: a case of unusual
      location of echinococcosis.
AB  - Hydatid disease is a parasitic disease most commonly caused by Echinococcus
      granulosus that seldom involves the skeleton and is still common in the countries
      of the temperate zones. We present an extremely rare case report of a young
      patient with humeral hydatid disease complicated with extraosseous involvement.
      Plain film of the left humerus demonstrated distortion of the axis, regional
      expansion of the humeral shaft with minimal thinning areas of the cortex.
      Additionally, numerous radiolucent areas of the humeral shaft were observed
      especially at the distal part of the bone. No calcification of the soft tissues
      was noticed. Computed tomography examination showed significant destruction of
      the trabecular bone of the humeral head and polycystic appearance of the bone
      marrow with regional calcifications into the lumen. Additionally, a large cystic
      lesion between medial and lateral head of the triceps muscle with some foci of
      calcifications were observed. Magnetic resonance imaging revealed the multiocular
      nature of the lesion into the humeral lumen with a cystic lesion involving the
      soft tissues of the upper arm. The cyst showed contrast enhancement at the
      pericyst capsule of the cyst after Gadolinium-DTPA administration.

PMID- 11223481
TI  - Malignant hypophosphathaemic bone disease.
AB  - A case of crippling osteoporosis with muscular weakness, hypophosphatemia,
      hyperparathyroidism, defective skeletal calcification and cartilage destruction
      is reported. The patient, a male was observed from the age of 2 1/2 until his
      death at the age of 33 years. This bone/cartilage disease failed to respond to
      phosphate supplementation, parathyroidectomy and calcitriol. We believe this may
      represent a hitherto undescribed entity.

PMID- 11223482
TI  - Only by public consent.

PMID- 11223483
TI  - Living with heart disease: the 2001 Annual Report Card on the Health of
      Canadians.

PMID- 11223484
TI  - The most chronic disease.

PMID- 11223485
TI  - Exercise in the primary prevention of coronary artery disease.
AB  - Since the 1950s there has been a steady accumulation of data from observational
      studies and clinical trials identifying a lack of physical activity, either in
      the industrial or leisure setting, as an independent major risk factor for
      coronary artery disease, with a similar relative risk as smoking,
      hypercholesterolemia and hypertension. More recently, poor cardiorespiratory
      fitness has also been shown to increase the risk of cardiovascular mortality
      significantly. Regular exercise is now known to have beneficial effects on
      peripheral and central circulation, skeletal muscle and myocardium, as well as
      lipid and carbohydrate metabolism. Individuals who become active in later life,
      for example, by way of a moderate intensity walking program, and who make only
      modest gains in fitness, nevertheless share in many of these health benefits and
      reduce their coronary artery disease risk. It is estimated that 60% of Canadians
      are physically inactive, a higher prevalence than for the other major risk
      factors. Consequently, efforts to encourage a more active lifestyle can have a
      significant impact on cardiovascular morbidity and mortality, with a marked
      reduction in costs to the health care system.

PMID- 11223486
TI  - Isolated left ventricular abnormal trabeculation: follow-up and association with
      neuromuscular disorders.
AB  - OBJECTIVES: To assess in patients with isolated left ventricular abnormal
      trabeculation (ILVAT), by a prospective follow-up study, whether the
      echocardiographic appearance of ILVAT changes, whether cardiac symptoms change,
      how many patients are hospitalized because of cardiac problems or die, and
      whether ILVAT is associated with neuromuscular disorders in all patients.
      PATIENTS AND METHODS: ILVAT was diagnosed in 33 patients--nine women and 24 men-
      aged 30 to 73 years. At baseline, all patients underwent a cardiological and
      neurological investigation. Between October and December 1999 they were invited
      for a clinical and echocardiographic follow-up. results: During a mean follow-up
      duration of 19 months, ILVAT remained unchanged. Cardiac symptoms worsened in one
      patient and improved in 10. Five patients were hospitalized and four patients
      died, two of them suddenly. ILVAT was associated with neuromuscular disorders in
      26 patients (81%). conclusions: Although ILVAT does not change over time, cardiac
      function may deteriorate. Because the rate of arrhythmias is high and even causes
      death in some patients, effective antiarrhythmic therapy should be considered.
      ILVAT is assumed to be a cardiac manifestation of a neuromuscular disorder or a
      special type of a cardiomyopathy.

PMID- 11223487
TI  - Intensive surveillance and treatment of dyslipidemia in the postinfarct patient:
      evaluation of a nurse-oriented management approach.
AB  - BACKGROUND: Lowering plasma low density lipoprotein (LDL) cholesterol
      concentrations in patients with established coronary artery disease is essential
      if recurrent cardiac events and mortality are to be prevented; however, a large
      proportion of patients with myocardial infarction (MI) are not screened and
      treated appropriately in the months immediately following hospital discharge.
      OBJECTIVES AND METHODS: The CHOlesterol Post-INfarct (CHOPIN) project is a nurse
      centred program initiated to close the large gap between nationally centred
      recognized guidelines for LDL lowering and current actual practice in the
      secondary prevention of coronary artery disease. RESULTS: The authors report
      findings in 151 consecutive patients (70 years of age or less) followed for an
      average of 5.5+/-3.3 months. Three months after an index MI and at a time when
      patients started being followed in CHOPIN, 46% of patients had LDL in excess of
      2.5 mmol/L and 36% had LDL greater than 3.20 mmol/L. LDL-lowering interventions
      undertaken comprised either consultation with a dietitian (35%) or initiation or
      modification of lipid-lowering medication (58%). Mean LDL on discharge from
      CHOPIN was 2.58+/-0.49 mmol/L, and 97% of the patients had LDL cholesterol less
      than 3.20 mmol/L at discharge. CONCLUSIONS: This experience shows that a nurse
      based case management strategy can achieve good control of dyslipidemia in a
      large proportion of post-MI patients. Because intervention to lower LDL has been
      prospectively shown to reduce the need for coronary artery bypass and
      angioplasty, these results suggest that projects configured in the manner of
      CHOPIN should reduce hospital costs associated with cardiovascular disease.

PMID- 11223488
TI  - The management of patients who have suffered an acute myocardial infarction in a
      tertiary care centre.
AB  - BACKGROUND: The standard of management after acute myocardial infarction (MI)
      includes beta-blockers and acetylsalicylic acid (ASA). Angiotensin-converting
      enzyme (ACE) inhibitors and lipid-lowering agents are indicated for some
      patients, and calcium channel blockers should generally be avoided. It is
      suspected that many patients with MI are not discharged from hospital with
      optimal medical management. OBJECTIVES: To determine what proportion of patients
      in a tertiary care hospital with acute MI are discharged on optimal medical
      therapy, and to identify what barriers exist to obtaining optimal treatment for
      as many patients as possible. PATIENTS AND METHODS: Charts were retrospectively
      reviewed for 717 patients with acute MI admitted to the Queen Elizabeth II Health
      Sciences Centre, Halifax, Nova Scotia from January 1, 1997 to April 30, 1999.
      Charts were reviewed for demographics, comorbidities, investigations performed,
      and medications on admission and discharge. When discharge medications did not
      match the optimal medical management, the chart was reviewed for the reasoning
      behind the decisions. RESULTS: In-hospital mortality was 9.6%. Among 648 patients
      who survived to discharge, 577 (89.0%) were discharged on a beta-blocker, 261
      (40.3%) on an ACE inhibitor, 105 (16.2%) on a calcium channel blocker and 578
      (89.2%) on ASA. Patients 65 years of age or older were less likely than their
      younger counterparts to be discharged on a beta-blocker (272 of 315 [86.3%]
      versus 305 of 333 [91.6%], P<0.04) and more likely to be discharged on a calcium
      channel blocker (70 of 315 [22.2%] versus 35 of 333 [10.5%], P<0.0001). No
      significant difference in the use of beta-blockers or calcium channel blockers
      was found between men and women (beta-blockers: 385 of 432 [89.1%] men versus 192
      of 216 [89.9%] women, P<0.92); calcium channel blockers (67 of 432 men [15.5%]
      versus 38 of 216 women [17.6%], P<0.50). Among patients with low density
      lipoprotein greater than 3.5 mmol/L, 158 of 200 (79.0%) were discharged on a
      lipid-lowering agent. Among patients with documented ejection fraction less than
      40%, 94 of 103 (91.3%) were discharged on an ACE inhibitor. Most patients had
      acceptable contraindications to the medications that they did not receive.
      CONCLUSIONS: The study centre showed much better use of appropriate medications
      than has been previously described, showing that optimal medical therapy can be
      achieved for the vast majority of patients with acute MI.

PMID- 11223489
TI  - Origins of heart rate variability: autonomic blockade of large magnitude,
      transient bradycardia in conscious rabbits.
AB  - BACKGROUND: Heart period sequences are composed of recurrent, similarly shaped,
      physiologically meaningful, transient heart period structures. One such structure
      is a large magnitude transient bradycardia (LMTB), which resembles published
      reports of responses to alerting stimuli. Alerting responses are sensitive to
      alpha1-adrenoceptor and cholinergic receptor blockade. OBJECTIVES: To determine
      whether LMTBs are related to alerting responses by assessing the response of
      rabbit LMTBs to autonomic inhibitors. ANIMALS AND METHODS: Using a Latin square,
      crossover design, six conscious, unsedated rabbits received placebo,
      intramuscular glycopyrrolate 0.05 mg/kg and intravenous prazosin 0.15 mg/kg, and
      six rabbits received placebo, intravenous metoprolol 0.15 mg/kg and intravenous
      ICI-118,551 0.1 mg/kg. Heart period and blood pressure were continuously
      recorded, digitized and analyzed off-line. RESULTS: LMTBs were suppressed by 93%
      and 95% by alpha1-adrenergic and muscarinic blockade, respectively, but not by
      beta1-adrenergic or beta2-adrenergic blockade. The drugs altered none of the
      morphological parameters of shape, magnitude or duration, or any of the
      hypotensive features. CONCLUSIONS: LMTBs are similar to alerting responses; they
      are both expressed as transient hypotensive and bradycardic events that are
      markedly reduced by muscarinic and alpha1-adrenoceptor blockade but not by beta
      adrenoceptor blockade. The presence of LMTBs may indicate ongoing, subtle changes
      in the laboratory environment.

PMID- 11223490
TI  - Myectomy for hypertrophic obstructive cardiomyopathy after failed alcohol septal
      ablation: clinicopathological correlations.
AB  - Hypertrophic cardiomyopathy - a genetically transmitted cardiac disorder - has
      diverse clinical, pathological and molecular manifestations. Echocardiography is
      the most reliable tool for clinical diagnosis of hypertrophic cardiomyopathy.
      Reduction of the intraventricular pressure gradient and improvement of symptoms
      are major objectives of all therapeutic strategies. The recently introduced
      concept of catheter-based interventional treatment involves selective coronary
      perforator branch injection of 96% ethanol to reduce septal thickness, left
      ventricular outflow obstruction, left ventricular filling pressure and symptoms.
      The long term morphological features after medical ablation are presented for the
      first time and compared with both the echocardiographic findings and the findings
      reported in the English-language literature. The findings show that injection of
      ethanol into the perforator branch is associated with a fairly localized area of
      myocardial scarring.

PMID- 11223491
TI  - Transient dobutamine-mediated pulsus alternans.
AB  - Pulsus alternans, alternating weak and strong beats occurring in a heart beating
      at a constant rate, has most often been reported in patients with severe, end
      stage heart failure. This patient with New York Heart Association functional
      class I heart failure developed pulsus alternans during the inotropic stimulation
      of dobutamine that subsequently resolved in a time course consistent with
      dobutamine clearance. Thus, in the setting of mildly impaired myocardial
      contractility, the inotropic stimulus of dobutamine may precipitate the
      development of reversible pulsus alternans.

PMID- 11223492
TI  - Diagnosis of left atrial sarcoma by transvenous endocardial biopsy.
AB  - A case of left atrial sarcoma in which the diagnosis was made by transvenous
      biopsy using the trans-septal approach is reported. The procedure was monitored
      by transesophageal echocardiography.

PMID- 11223493
TI  - The Canadian health care system: should someone write a "do not resuscitate"
      order?

PMID- 11223494
TI  - Doctors as patients.

PMID- 11223495
TI  - Respiratory medicine: increasing demands.

PMID- 11223496
TI  - Nicotine replacement combined with a novel compound (ProBAN) for smoking
      cessation: a pilot study.
AB  - BACKGROUND: Smoking cessation rates with available pharmacological therapies
      remain suboptimal. Anecdotal observations with a combination of sublingual
      pralidoxime and ipratropium (ProBAN) suggested that these agents in combination
      with nicotine gum improved quit rates. OBJECTIVE: To determine whether ProBAN
      together with nicotine replacement improves quit rates compared with nicotine
      replacement alone. DESIGN: A 12-week, prospective, double-blind, randomized,
      placebo controlled pilot study. SETTING: University-affiliated outpatient clinic.
      POPULATION STUDIED: Healthy adult smokers were recruited via advertisements. Of
      107 subjects seen at the screening visit, 27 were excluded because of comorbid
      illness or concomitant medication use. INTERVENTIONS: Of 80 eligible subjects, 40
      were randomly assigned to receive treatment with ProBAN sub- lingual tablets and
      nicotine gum (treatment group), and 40 to receive placebo tablets and nicotine
      gum (control group) for 12 weeks. The primary outcome was complete continuous
      abstinence of smoking from one through 12 weeks after the quit date. MAIN
      RESULTS: There were no adverse effects in the treatment group. At one week after
      the quit date, 35% of ProBAN-treated subjects had quit compared with 18% of
      control subjects (odds ratio [OR] 2.5, 95% CI 0.9 to 7.2). Corresponding quit
      rates at four weeks were 28% and 15% (OR 2.1, 95% CI 0.7 to 6.5), at eight weeks
      were 25% and 13% (OR 2.3, 95% CI 0.7 to 7.6), and at 12 weeks were 23% and 13%
      (OR 2.0, 95% CI 0.6 to 6.7), respectively. CONCLUSIONS: This pilot study
      indicated that ProBAN combined with nicotine replacement doubled the continuous
      sustained quit rate compared with nicotine replacement alone, with no adverse
      effects. Although not statistically significant due to the size of the study,
      this result suggests that it may be an effective therapy for smoking cessation,
      and larger studies are warranted.

PMID- 11223497
TI  - Economic impact of using an immunostimulating agent to prevent severe acute
      exacerbations in patients with chronic obstructive pulmonary disease.
AB  - RATIONALE: OM-85 BV, an immunostimulant made from bacterial extracts, has been
      shown to reduce the risk of hospitalization for acute exacerbation in patients
      with chronic obstructive pulmonary disease, as well as to reduce the length of
      stay for all hospitalizations. METHODS: In conjunction with a placebo controlled,
      randomized clinical trial, a cost effectiveness analysis was carried out to
      assess the economic impact of using OM-85 BV. In the analysis, effectiveness was
      defined as the difference in the number of severe acute exacerbations, assessed
      by the number of hospitalizations for a respiratory problem, between the placebo
      and OM-85 BV-treated groups. RESULTS: The median cost to prevent one day of
      hospitalization for a respiratory condition was CDN$45, with a 95% CI of CDN$18
      to CDN$210. Bootstrap of the study population and sensitivity analyses showed
      that the results were robust and not likely due to random fluctuation; 98.8% of
      the cost effectiveness and 96.8% of the cost-benefit ratios favoured the use of
      OM-85 BV. Indirect costs, defined as a need for help, were reduced by 36% in the
      group treated with OM-85 BV: 779 h of help compared with 1212 h in the placebo
      group. This trend, while not significant, is consistent with other results and
      suggests a decrease in the severity of exacerbations in the OM-85 BV-treated
      group. CONCLUSION: Given the high prevalence of chronic obstructive pulmonary
      disease worldwide and the high cost of acute exacerbations, immunostimulants may
      become a key element in the improved control of this condition.

PMID- 11223498
TI  - Post-Christmas blues: a rare cause of cyanosis.
AB  - A patient was referred for urgent evaluation of cyanosis. Although she had
      symptoms and signs of an upper respiratory tract infection, she had a normal
      cardiorespiratory examination and normal transcutaneous oxygen saturation.
      Further evaluation revealed a benign cause for the cyanosis.

PMID- 11223500
TI  - The pair-functional method for direct solution of molecular structures. I.
      Statistical principles.
AB  - The pair-functional principle shows how to construct a unique statistical
      ensemble of strongly interacting atoms that corresponds to any feasible measured
      set of X-ray intensities. The ensemble and all its distribution functions are
      strictly periodic in the crystal lattice, so that each unit cell has exactly the
      same arrangement of atoms at all times. The mean particle density in the cell is
      uniform because the ensemble has undefined phases and the origin is not fixed.
      The atoms in this maximum-entropy ensemble interact through pairwise additive
      periodic statistical forces within the unit cell. The ensemble average pair
      correlation function is matched to the observed originless Patterson function of
      the crystal. The derived pairing force then becomes approximately proportional to
      the Ornstein-Zernicke direct correlation function of the ensemble. The atoms have
      a many-body Boltzmann distribution and the logarithm of the likelihood of any
      particular conformation is related to its total pairing potential. The pairing
      potential of a group of atoms acts like a local field in the cell. This property
      is used in the pair-functional method. Molecular structures can be solved by a
      direct search in real space for clusters of atoms with high pair potentials.
      During a successful search, the atoms move from their original random positions
      to form larger and larger clusters of correctly formed fragments. Finally, every
      atom belongs to a single cluster, which is the correct solution.

PMID- 11223501
TI  - The pair-functional method for direct solution of molecular structures. II. Small
      molecule tests.
AB  - The new pair-functional direct method has been implemented and tested. Like the
      Patterson function, the pairing force has valuable imaging properties at high
      resolution. Two simple iterative algorithms were designed to refine on the total
      pair potential and the normalized intensity correlation coefficient of an atomic
      model. The first algorithm is a peak-picking method which selects the best-paired
      high peaks from a density map and then uses the strong reflections to generate a
      new Fourier filtered map. The second algorithm, the pair-and-square method, uses
      a tangent formula step instead of the Fourier and is a little more efficient.
      Computational experiments on a point-atom grid model, with perfect data, reached
      exact ab initio solutions for up to 600 atoms. Point-atom models were also solved
      by searching for reduced structures that contained as few as one quarter of the
      atoms. Seeded searches, guided by a small known fragment, solved up to 30000
      atoms on the grid. Realistic tests on actual molecules showed that Sheldrick's
      [Acta Cryst. (1990), A46, 467-473] test structures of 50-200 atoms can be solved
      under a variety of conditions.

PMID- 11223502
TI  - The pair-functional method. III. The pairing forces.
AB  - The theory of the pair-functional ensemble is developed to provide estimates of
      the pairing forces from experimental X-ray intensities. The statistical mechanics
      of the grand ensemble leads to a diagram expansion for the forces, in terms of
      the direct correlation function of the fluid ensemble combined with a series of
      small higher-order corrections. A simpler treatment, based on a biased Gaussian
      probability distribution, gives approximate formulae, valid for reflections of
      any type in all space groups. The role of symmetry is analysed. The entropy of an
      asymmetrical ensemble can always be increased by averaging it over equivalent
      positions of the atoms in the true space group, with the result that the atoms
      naturally tend to adopt the highest symmetry compatible with the data. In a cell
      with different types of atom, the atoms experience a single force function but
      they interact with a strength proportional to the products of their scattering
      factors. Numerical estimates are given for typical cases.

PMID- 11223503
TI  - An exponential modeling algorithm for protein structure completion by X-ray
      crystallography.
AB  - An exponential modeling algorithm is developed for protein structure completion
      by X-ray crystallography and tested on experimental data from a 59-residue
      protein. An initial noisy difference Fourier map of missing residues of up to
      half of the protein is transformed by the algorithm into one that allows easy
      identification of the continuous tube of electron density associated with that
      polypeptide chain. The method incorporates the paradigm of phase hypothesis
      generation and cross validation within an automated scheme.

PMID- 11223504
TI  - On the transition from the wurtzite to the NaCl type.
AB  - A crystallographic interpretation of a possible transition mechanism from the
      wurtzite to the NaCl type is given. For this purpose, different atoms in the
      structures of both types are replaced by like ones, resulting in lonsdaleite-type
      configurations and in cubic primitive lattices, respectively. The atomic
      arrangements of both types correspond to homogeneous sphere packings. It is shown
      that a lonsdaleite configuration may be deformed into a cubic primitive lattice
      within the Wyckoff position Cmcm 8(f) m. 0,y,z. Such a transition is displacive
      since no bonds have to be broken. The corresponding phase transformation from the
      wurtzite to the NaCl type can be described as a deformation of a heterogeneous
      sphere packing. The intermediate structure would have the symmetry Cmc2(1).

PMID- 11223505
TI  - Electron crystallography without limits? Crystal structure of Ti45Se16
      redetermined by electron diffraction structure analysis.
AB  - The crystal structure of the metal-rich compound Ti(45)Se(16) was redetermined
      from selected-area electron diffraction film data. The structure was solved by
      quasi-automatic direct methods using a data set of quantified h0l electron
      diffraction intensities. Improved atomic coordinates were obtained from a
      subsequent least-squares refinement on the basis of the kinematical
      approximation. The compound crystallizes in the monoclinic space group C2/m with
      lattice parameters a = 36.534, b = 3.453, c = 16.984 A, beta = 91.73 degrees. The
      structure contains 23 titanium and 8 selenium atoms per asymmetric part of the
      unit cell. The refined atomic coordinates agree on average within 0.18 A with the
      previously determined structure from high-resolution electron-microscopy images.
      The precision of the determined atomic coordinates obtained in this study is
      better than 0.05 A. The structure of Ti(45)Se(16) is the eighth metal-rich
      structure that has been solved by direct methods from two-dimensional selected
      area electron diffraction data using the quasi-kinematical approximation. The
      present investigation proves again that direct methods with electron diffraction
      data work extremely reliably provided that the structure in question is composed
      of elements of nearly equal scattering power and that data covering the most
      significant parts of the unit-cell transform up to atomic resolution are
      available. Moreover, a method was developed that allows the estimation of the
      average crystal thickness from the effective atomic potential in the refined
      structure.

PMID- 11223506
TI  - Strength tuning of multiple waves in crystals.
AB  - In this work, the linear polarization of synchrotron radiation is explored as a
      tuning key for the strength of the simultaneously diffracted X-ray waves in
      crystals. The relative strength of the waves has been defined by the
      reflectivities of the Bragg reflections involved in each multiple-diffraction
      case and it has limited the applicability of the multiple-diffraction phenomenon.
      With a proper choice of the wavelength and the polarization direction of the
      incident synchrotron radiation, it is demonstrated how the intensity ratios of
      the simultaneously diffracted beams can be drastically changed.

PMID- 11223507
TI  - Quantitative determination of the spatial coherence from the visibility of equal
      thickness fringes.
AB  - Spatial coherence of the undulator radiation in the horizontal direction is
      measured by a wedge-shaped crystal interferometer. The Borrmann effect, the
      effect of the angular divergence of the incidence and the wavefront matching of
      the collimating asymmetric diffractions with the interferometer are discussed to
      estimate the coherence factor. The spatial coherence length of 145 microm is
      experimentally determined, which is enhanced by the collimators about 100 times
      more than expected from the source size.

PMID- 11223508
TI  - Generalized extinction in bipyramidal crystals.
AB  - The generalized extinction factors for a set of strong reflections as a function
      of wavelength are obtained by indirect measurements. The experiments are
      performed on a crystalline system that satisfies the geometrical requirements
      imposed by theoretical models developed for a finite perfect crystal. With
      increased perfection, represented by a reduction in the width of the mosaic
      distribution function from three to one thousandth of a degree, the experiments
      give results that approach the predictions from the theory. The present procedure
      utilizes measurements of the integrated diffracted power of a weak reflection for
      scaling the strong reflections, hence non-measurable wavelength-dependent factors
      are assumed to be eliminated.

PMID- 11223509
TI  - A note on the problem of scattering from a single atomic plane and a stack of
      planes. Differences between the Ewald and other diffraction theories.
AB  - The scattering of a scalar plane wave (neutrons) from a single atomic plane
      consisting of any two-dimensional lattice with a basis is studied using the Ewald
      dynamical theory of diffraction. Formulae for the reflection and transmission
      coefficients obtained by evaluating the optical plane lattice sums are valid for
      general geometries, including nonsymmetrical and noncoplanar diffractions. The
      approach adopted is different from and more general than that by Yashiro &
      Takahashi [Acta Cryst. (2000), A56, 1663-167]. The structure factor yielded by
      this procedure differs from that used in the kinematical or Laue dynamical
      diffraction theories.

PMID- 11223510
TI  - X-ray determination of Debye-Waller factors and Debye temperatures of h.c.p.
      elements Ti, Zr, Ru, Tm, Hf.
AB  - Debye-Waller factors of five h.c.p. elements (Ti, Zr, Ru, Tm, Hf) have been
      determined from X-ray diffraction intensities. Within the limits of experimental
      errors, the Debye-Waller factors associated with the two principal directions are
      equal. The Debye temperatures (straight theta(M)) have been evaluated. The energy
      of formation of vacancies (E(f)) has been estimated from a semi-empirical
      relation between E(f) and straight theta.

PMID- 11223511
TI  - Structure of the M148Q mutant of rusticyanin at 1.5 A: a model for the copper
      site of stellacyanin.
AB  - The small blue copper protein rusticyanin from Thiobacillus ferrooxidans contains
      a type 1 Cu centre with a single axial ligand, Met148, which together with the
      His-Cys-His trigonal planar ligands produces a distorted trigonal pyramidal
      coordination geometry to copper. Type 1 Cu sites are found in cupredoxins and
      several multicopper proteins, including oxidases and nitrite reductases. The role
      of the axial ligand has been extensively debated in terms of its function in the
      fine tuning of the redox potential and spectroscopic properties of type 1 Cu
      sites. Numerous mutations of the Met ligand in azurins have been studied, but
      interpretation of the results has been complicated by the presence of the
      additional carbonyl oxygen ligand from Gly45, a neighbouring residue to the
      coordinating His46. The importance of the axial ligand has been further
      emphasized by the finding that the type 1 centre in Rhus vernicifera
      stellacyanin, with the lowest redox potential in a type 1 Cu site of 184 mV, has
      Gln as the axial ligand, whilst fungal laccase and ceruloplasmin, which have
      redox potentials of 550-800 mV, have a Leu in this position. Here, the crystal
      structure of the M148Q mutant of rusticyanin at 1.5 A resolution is presented.
      This is a significantly higher resolution than that of the structures of native
      rusticyanin. In addition, the M148Q structure is that of the oxidized protein
      while the native structures to date are of the reduced protein. The mutant
      protein crystallizes with two molecules per asymmetric unit, in contrast to the
      one present in the native crystal form. This mutant's redox potential (550 mV at
      pH 3.2) is lowered compared with that of the native protein ( approximately 670
      mV at pH 3.2) by about 120 mV. The type 1 Cu site of M148Q closely mimics the
      structural characteristics of the equivalent site in non-glycosylated cucumber
      stellacyanin (redox potential approximately 260 mV) and, owing to the absence in
      rusticyanin of the fifth, carbonyl ligand present in azurin, may provide a better
      model for the R. vernicifera stellacyanin (redox potential approximately 184 mV)
      type 1 Cu site, which also lacks the fifth ligand. Furthermore, the presence of
      two molecules in the asymmetric unit cell indicates a potential binding region of
      the redox partners.

PMID- 11223512
TI  - Structure of a new 'aspzincin' metalloendopeptidase from Grifola frondosa:
      implications for the catalytic mechanism and substrate specificity based on
      several different crystal forms.
AB  - Crystal structures of a peptidyl-Lys metalloendopeptidase (MEP) from the edible
      mushroom Grifola frondosa (GfMEP) were solved in four crystal forms. This
      represents the first structure of the new family 'aspzincins' with a novel active
      site architecture. The active site is composed of two helices and a loop region
      and includes the HExxH and GTxDxxYG motifs conserved among aspzincins. His117,
      His121 and Asp130 coordinate to the catalytic zinc ligands. An electrostatically
      negative region composed of Asp154 and Glu157 attracts a positively charged Lys
      side chain of a substrate in a specific manner. A Tyr133 side chain located on
      the S1' pocket had different configurations in two crystal forms and was not
      observed in the other crystal forms. The flexible Tyr133 plays two roles in the
      enzymatic function of GfMEP. The first is to provide a hydrophobic environment
      with Phe83 in order to accommodate the alkyl part of the Lys side chain of a
      substrate and the second is as a 'proton donor' to the oxyanion of the
      tetrahedral transition state to stabilize the reaction transition state.

PMID- 11223513
TI  - Structures of two highly homologous bacterial L-asparaginases: a case of
      enantiomorphic space groups.
AB  - Quasi-enantiomorphic crystals of the Y25F mutant of Escherichia coli L
      asparaginase and of the native Erwinia chrysanthemi L-asparaginase were obtained
      in the hexagonal space groups P6(5)22 and P6(1)22, respectively. The structures
      of these highly homologous enzymes were solved by molecular replacement and were
      refined with data extending to 2.2-2.5 A. These structures were compared with
      each other, as well as with other L-asparaginase structures previously observed
      with different crystal packing. It is concluded that the observed phenomenon,
      which is rare, was most likely to have arisen by chance.

PMID- 11223514
TI  - Structure of fibroblast growth factor 9 shows a symmetric dimer with unique
      receptor- and heparin-binding interfaces.
AB  - Fibroblast growth factors (FGFs) constitute a family of at least 20 structurally
      related heparin-binding polypeptides active in regulating cell growth, survival,
      differentiation and migration. FGF9, originally discovered as a glia-activating
      factor, shares 30% sequence identity with other FGFs and has a unique spectrum of
      target-cell specificity. FGF9 crystallized in the tetragonal space group I4(1),
      with unit-cell parameters a = b = 151.9, c = 117.2 A. The structure of the
      glycosylated protein has been refined to an R value of 21.0% with R(free) =
      24.8%) at 2.6 A resolution. The four molecules in the asymmetric unit are
      arranged in two non-crystallographic dimers, with the dimer interface composed
      partly of residues from N- and C-terminal extensions from the FGF core structure.
      Most of the receptor-binding residues identified in FGF1- and FGF2-receptor
      complexes are buried in the dimer interface, with the beta8-beta9 loop stabilized
      in a particular conformation by an intramolecular hydrogen-bonding network. The
      potential heparin-binding sites are in a pattern distinct from FGF1 and FGF2. The
      carbohydrate moiety attached at Asn79 has no structural influence.

PMID- 11223515
TI  - Anisotropic refinement of the structure of Thermoascus aurantiacus xylanase I.
AB  - The isotropic crystallographic model of the structure of xylanase I from
      Thermoascus aurantiacus (TAXI) has now been refined anisotropically at 1.14 A
      resolution to a standard residual of R = 11.1% for all data. TAXI is amongst the
      five largest proteins deposited in the Protein Data Bank to have been refined
      with anisotropic displacement parameters (ADPs) at this level of resolution. The
      anisotropy analysis revealed a more isotropic distribution of anisotropy than
      usually observed previously. Adding ADPs resulted in high-quality electron
      density maps which revealed discrepancies from the previously suggested primary
      sequences for this enzyme. Side-chain conformational disorder was modelled for 16
      residues, including Trp275, a bulky residue at the active site. An unrestrained
      refinement was consistent with the protonation of the catalytic acid/base
      glutamate and the deprotonation of the nucleophile glutamate, as required for
      catalysis. The thermal stability of TAXI is reinterpreted in the light of the new
      refined model.

PMID- 11223516
TI  - Crystallographic phasing of myristoyl-CoA-protein N-myristoyltransferase using an
      iodinated analog of myristoyl-CoA.
AB  - Myristoyl-CoA-protein N-myristoyltransferase (Nmt; E.C. 2.1.3.97) catalyzes the
      covalent attachment of myristate to the N-terminal glycine amine of many
      eukaryotic and viral proteins. The molecular structure of the ternary complex of
      Saccharomyces cerevisiae Nmt1p with a bound non-hydrolyzable myristoyl-CoA
      analog, S-(2-oxopentadecyl)-CoA, and a competitive peptidomimetic inhibitor, SC
      58272, was solved to 2.9 A resolution by X-ray crystallography. The structure
      determination utilized diffraction data from an iodinated ternary complex in
      which a newly designed and synthesized compound, S-(13-iodo-2-oxotridecyl)-CoA,
      was substituted for S-(2-oxopentadecyl)-CoA. Replacing the two terminal fatty
      acid C atoms of myristate by iodine produced, under the same crystallization
      conditions, heavy-atom-derivatized crystals of defined site occupancy that were
      isomorphous to the native complex. This approach for obtaining experimental phase
      information can be extended to other crystal structures of protein-fatty acyl
      complexes. The synthesis of S-(13-iodo-2-oxotridecyl)-CoA and the phasing
      procedure are described.

PMID- 11223517
TI  - Geometry of metal-ligand interactions in proteins.
AB  - The geometry of metal-ligand interactions in proteins is examined and compared
      with information for small-molecule complexes from the Cambridge Structural
      Database (CSD). The paper deals with the metals Ca, Mg, Mn, Fe, Cu, Zn and with
      metal-donor atom distances, coordination numbers and extent of distortion from
      ideal geometry (octahedral, tetrahedral etc.). It assesses the agreement between
      geometry found in all metalloprotein structures in the Protein Data Bank (PDB)
      determined at resolution < or = 1.6 A with that predicted from the CSD for
      ligands which are analogues of amino-acid side chains in proteins [Harding
      (1999), Acta Cryst. D55, 1432-1443; Harding (2000), Acta Cryst. D56, 857-867].
      The agreement is reasonably good for these structures but poorer for many
      determined at lower resolution (examined to 2.8 A resolution). For metal-donor
      distances, the predictions from the CSD, with minor adjustments, provide good
      targets either for validation or for restraints in refinement of structures where
      only poorer resolution data is available. These target distances are tabulated
      and the use of restraints is recommended. Validation of angles or the use in
      refinement of restraints on angles at the metal atom is more difficult because of
      the inherent flexibility of these angles. A much simplified set of parameters for
      angle restraints with quite large standard deviations is provided. (Despite the
      flexibility of the angles, acceptable and preferred coordination numbers and
      shapes are well established and a summary table is provided.) An unusual and
      perhaps biochemically important feature of Zn coordination with carboxylate seen
      in the CSD examples is also clearly present in metalloprotein structures. With
      metals like Ca, carboxylate coordination is monodentate or bidentate (two M-O
      bonds of nearly equal length). In Zn carboxylates a continuous range between
      monodentate and bidentate coordination is found, with one Zn-O bond of normal
      length and another of any length between this and a van der Waals contact.

PMID- 11223518
TI  - Experimental evidence for the stability of the depletion zone around a growing
      protein crystal under microgravity.
AB  - Experimental evidence is presented for the first time for the development and
      time evolution of concentration-depletion zones around protein crystals growing
      in microgravity and gelled on-ground experiments. Crystal motion and buoyancy
      driven fluid movements as a result of residual accelerations and g-jitters are
      demonstrated to have an adverse effect on the stability of these depletion zones,
      provoking the breakdown of their radial symmetry. These findings may explain some
      of the controversial results reported on the quality of single crystals grown
      under microgravity in previous space missions.

PMID- 11223519
TI  - Crystallization and preliminary X-ray analysis of the recombinant dihaem
      cytochrome c (NapB) from Haemophilus influenzae.
AB  - The napB gene of the pathogenic bacterium Haemophilus influenzae encodes a dihaem
      cytochrome c, the small subunit of a heterodimeric periplasmic nitrate reductase
      (Nap). Recombinant NapB was overproduced in Escherichia coli, purified to near
      homogeneity and crystallized using the hanging-drop method. Thin quadrilateral
      plates were grown under various conditions but proved to be unsuitable for X-ray
      analysis. However, a single crystal was grown using 1.75 M ammonium sulfate in
      0.1 M sodium acetate pH 5.5, from which a native data set could be collected to
      1.8 A resolution using synchrotron radiation. Using the same conditions, further
      crystals were obtained by microseeding. The space group was determined to be
      P42(1)2, with unit-cell parameters a = 77.55, b = 77.55, c = 28.64 A and an
      unusually low solvent content of 16.5%, assuming there to be one molecule of NapB
      in the asymmetric unit. Analysis of the dissolved crystals indicated that partial
      proteolysis of the protein had occurred. Taking the molecular mass of the
      crystallized form ( approximately 8500 Da) into account, the solvent content was
      estimated to be 53%, with a V(M) value of 2.64 A(3) Da(-1).

PMID- 11223520
TI  - Crystallization of the Bacillus subtilis RTP-DNA complex prepared using NMR
      spectroscopy.
AB  - The replication terminator protein (RTP)-DNA complex of Bacillus subtilis is
      responsible for the arrest of DNA replication at terminator sites in the B.
      subtilis chromosome. The crystallization and preliminary diffraction data
      analysis for the complex of an (15)N-labelled mutant form of RTP and a
      symmetrical form of its DNA-binding site is reported. NMR spectroscopy was used
      to assess the stoichiometry of complex formation, with the sample containing the
      most homogeneous solution of complex giving rise to diffracting crystals.
      Synchrotron-radiation data to 2.5 A were collected from a crystal of space group
      P3(2)21, unit-cell parameters a = b = 44.780, c = 395.582 A, containing an RTP
      dimer within the asymmetric unit.

PMID- 11223521
TI  - Purification, crystallization and preliminary X-ray diffraction of anthocyanidin
      synthase from Arabidopsis thaliana.
AB  - Anthocyanidin synthase (ANS) from Arabidopsis thaliana is a non-haem iron(II)
      dependent dioxygenase reported to catalyse the conversion of leucoanthocyanidins
      to anthocyanidins. Anthocyanidins are precursors of anthocyanins, which are a
      major family of pigments in higher plants. ANS was crystallized by the vapour
      diffusion method using polyethylene glycol as a precipitant. The crystals belong
      to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a =
      61.0, b = 73.2, c = 87.0 A, and diffract to 2.4 A using Cu Kalpha radiation.

PMID- 11223522
TI  - Crystallization and characterization of the prolidase from Pyrococcus furiosus.
AB  - The prolidase (proline-specific amino dipeptidase) from the hyperthermophilic
      archaeon Pyrococcus furiosus has been crystallized. The enzyme has been shown to
      be a homodimer and to require two Co atoms per subunit for optimum activity. Two
      crystal forms have been obtained under similar growth conditions. Both are
      monoclinic, space group P2(1). Form I has unit-cell parameters a = 130.4, b =
      97.4, c = 129.9 A, beta = 118.3 degrees. Form II has a smaller unit cell, with a
      = 56.5, b = 97.3, c = 70.0 A, beta = 97.1 degrees. If the crystal density is
      assumed to lie near the center of the normal range then the form I crystals will
      have four dimers per asymmetric unit, whereas the form II crystals will have only
      one dimer in each asymmetric unit. Diffraction data have been recorded from
      native form I and form II crystals to resolutions of 3.2 and 1.95 A,
      respectively.

PMID- 11223523
TI  - Crystallization and preliminary X-ray crystallographic studies of recombinant
      human betaine-homocysteine S-methyltransferase.
AB  - Betaine-homocysteine S-methyltransferase (BHMT) catalyzes a reaction essential
      for regulation of methionine and homocysteine metabolism and the catabolism of
      choline in mammalian tissues. Human recombinant BHMT (MW = 45 kDa) has been
      crystallized by the hanging-drop vapor-diffusion method at 294 K using ethylene
      glycol as the precipitant. The crystals belong to the monoclinic space group C2,
      with unit-cell parameters a = 109.190, b = 91.319, c = 88.661 A, beta = 122.044
      degrees, and diffract to 2.9 A resolution on a local rotating-anode X-ray source.
      Rotation-function analysis and the Matthews coefficient, V(M) = 2.46 A(3) Da(-1),
      are consistent with a dimer in the asymmetric unit, suggesting that the active
      enzyme is a tetramer with 222 symmetry.

PMID- 11223524
TI  - Purification and crystallization of the human RXRalpha ligand-binding domain-9
      cisRA complex.
AB  - The purification and crystallization of the stoichiometric complex of human
      RXRalpha ligand-binding domain (hRXRalpha LBD) bound to its natural ligand 9-cis
      retinoic acid (9-cisRA) are described. A three-step purification yields a pure
      and homogeneous complex. Based on the crystallization conditions of several other
      nuclear receptors, an exhaustive crystallization screening using carboxylic acids
      as precipitating agents was performed in association with the use of polyhydric
      alcohols acting as cosmotropic solutes. Crystals of the hRXRalpha LBD-9-cisRA
      complex grew in a tripartite mixture containing sodium formate, glycerol and
      propane-1,2-diol. Micro- and macroseeding were necessary to improve both the size
      and the quality of crystals in order to make them suitable for structure
      determination.

PMID- 11223525
TI  - Crystallization and preliminary X-ray crystallographic analysis of RNase HIII
      from Bacillus subtilis.
AB  - The genome of Bacillus subtilis contains three different genes encoding RNase H
      homologs: RNases HI, HII and HIII. RNase HIII from B. subtilis degrades RNA in
      RNA-DNA hybrids in an Mg(2+)-dependent manner like Escherichia coli RNase HI.
      However, they belong to different classes; the former belongs to the 'class II'
      or 'large' RNase H family, while the latter belongs to the 'class I' or 'small'
      RNase H family. RNase HIII of B. subtilis has been overexpressed in E. coli and
      crystallized at 296 K using sodium formate as a precipitant. The native X-ray
      diffraction data have been collected to 2.8 A resolution using synchrotron
      radiation. The crystals are hexagonal, belonging to the space group P6(1), with
      unit-cell parameters a = b = 86.89, c = 214.49 A, alpha = beta = 90.0, gamma =
      120.0 degrees. A self-rotation function calculation indicated the presence of two
      monomers of the recombinant RNase HIII in the crystallographic asymmetric unit,
      giving a V(M) of 3.43 A(3) Da(-1) and a solvent content of 64.2%.

PMID- 11223526
TI  - Structural studies of a yeast quaternary transcription-initiation complex.
AB  - A 96.7 kDa quaternary transcription-factor complex consisting of the conserved
      core domains of yeast TBP, TFIIA, TFIIB and TATA-box DNA has been assembled from
      purified components. Crystals of the complex were obtained by the hanging-drop
      vapor-diffusion method. Native data sets were collected at synchrotron sources.
      Crystal form I belongs to space group R32, with unit-cell parameters a = b =
      173.2, c = 164.1 A, and diffracts to 2.5 resolution, but contains
      substoichiometric amounts of TFIIB. Crystal form II was assembled with a longer
      piece of DNA than that used for form I crystals and contains the complete
      quaternary complex. These crystals belong to space group P42(1)2, with unit-cell
      parameters a = b = 141.7, c = 112.0 A, and diffract to 3.6 A resolution.

PMID- 11223527
TI  - Crystallization and preliminary X-ray analysis of a NADPH 2-ketopropyl-coenzyme M
      oxidoreductase/carboxylase.
AB  - NADPH 2-ketopropyl-coenzyme M (2-mercaptoethanesulfonate)
      oxidoreductase/carboxylase is the terminal enzyme in a metabolic pathway that
      results in the conversion of propylene to the central metabolite acetoacetate.
      This enzyme is an FAD-containing enzyme that is a member of the NADPH:disulfide
      oxidoreductase family of enzymes and catalyzes the cleavage and carboxylation of
      2-ketopropyl-coenzyme M to form acetoacetate and coenzyme M. Crystallization
      trials have revealed that the highest diffraction quality crystals (better that
      2.0 A resolution) could be achieved when the substrate or product of the reaction
      was added to the enzyme in a stoichiometric excess.

PMID- 11223528
TI  - Purification, crystallization and preliminary crystallographic analysis of the
      periplasmic binding protein ProX from Escherichia coli.
AB  - A periplasmic binding protein (ProX) for the compatible solutes glycine betaine
      and proline betaine from Escherichia coli was crystallized using the hanging-drop
      vapour-diffusion method. Crystals were grown using a protein concentration of 10
      mg ml(-1) and a precipitant of 26-28% PEG 4000 in 50 mM PIPES pH 6.2-6.4. Native
      diffraction data to 1.93 A resolution have been obtained from crystals at 290 K.
      The crystals belong to the space group P2(1)2(1)2(1), with unit-cell parameters a
      = 48.1, b = 55.0, c = 115.7 A, and contain one molecule per asymmetric unit.

PMID- 11223529
TI  - Crystallization and preliminary X-ray analysis of the glycerol-3-phosphate 1
      acyltransferase from squash (Cucurbita moschata).
AB  - Glycerol-3-phosphate 1-acyltransferase (E.C. 2.3.1.15; G3PAT) catalyses the
      incorporation of an acyl group from either acyl-acyl carrier proteins (acylACPs)
      or acylCoAs into the sn-1 position of glycerol 3-phosphate to yield 1
      acylglycerol 3-phosphate. Crystals of squash G3PAT have been obtained by the
      hanging-drop method of vapour diffusion using PEG 4000 as the precipitant. These
      crystals are most likely to belong to space group P2(1)2(1)2(1), with approximate
      unit-cell parameters a = 61.1, b = 65.1, c = 103.3 A, alpha = beta = gamma = 90
      degrees and a monomer in the asymmetric unit. X-ray diffraction data to 1.9 A
      resolution have been collected in-house using a MAR 345 imaging-plate system.

PMID- 11223530
TI  - Purification, crystallization and preliminary X-ray diffraction analysis of the
      fructose-1,6-/sedoheptulose-1,7-bisphosphatase of Synechococcus PCC 7942.
AB  - Fructose-1,6-/sedoheptulose-1,7-bisphosphatase of Synechococcus PCC 7942,
      overexpressed from Escherichia coli, has been purified and crystallized by the
      hanging-drop vapour-diffusion method using ammonium sulfate as a precipitant. The
      crystals were monoclinic, with unit-cell parameters a = 80.1, b = 84.2, c = 104.3
      A, beta = 101.7 degrees. They belonged to space group P2(1) and diffracted to at
      least 2.2 A resolution. The calculated V(M) value, based on a tetramer in the
      asymmetric unit, was 2.2 A(3) Da(-1).

PMID- 11223531
TI  - Crystallization and preliminary X-ray analysis of a novel pectolytic enzyme,
      polymethoxygalacturonase SX1 from Trichosporon penicillatum.
AB  - A novel pectolytic enzyme, polymethoxygalacturonase SX1 from Trichosporon
      penicillatum, with a molecular weight of 36 kDa was crystallized by the hanging
      drop vapour-diffusion method using polyethylene glycol 1000 as a precipitant. The
      crystals belonged to the monoclinic space group C2, with unit-cell parameters a =
      165.6, b = 61.0, c = 48.7 A, beta = 93.1 degrees. The calculated V(M) based on
      one molecule per asymmetric unit was 3.40 A(3) Da(-1). A native data set was
      collected to 2.08 A resolution from a crystal on a Cu Kalpha rotating-anode X-ray
      source. A molecular-replacement solution was obtained using the program AMoRe and
      the structure of endopolygalacturonase II from Aspergillus niger as a model.

PMID- 11223532
TI  - Crystallization and preliminary X-ray diffraction studies of FHA domains of Dun1
      and Rad53 protein kinases.
AB  - Forkhead-associated (FHA) domains are modular protein-protein interaction domains
      of approximately 130 amino acids present in numerous signalling proteins. FHA
      domain-dependent protein interactions are regulated by phosphorylation of target
      proteins and FHA domains may be multifunctional phosphopeptide-recognition
      modules. FHA domains of the budding yeast cell-cycle checkpoint protein kinases
      Dun1p and Rad53p have been crystallized. Crystals of the Dun1-FHA domain exhibit
      the symmetry of the space group P6(1)22 or P6(5)22, with unit-cell parameters a =
      b = 127.3, c = 386.3 A; diffraction data have been collected to 3.1 A resolution
      on a synchrotron source. Crystals of the N-terminal FHA domain (FHA1) of Rad53p
      diffract to 4.0 A resolution on a laboratory X-ray source and have Laue-group
      symmetry 4/mmm, with unit-cell parameters a = b = 61.7, c = 104.3 A.

PMID- 11223533
TI  - Preliminary X-ray diffraction studies of the transcriptional inhibitory antibody
      Fab41.4.
AB  - The binding of transcription factor ATF-1 to DNA contributes to gene expression
      and regulation of cell growth. Antibody Mab41.4, raised against ATF-1, and its
      derivatives Fab41.4 and scFv41.4 inhibit specific DNA binding in vitro and induce
      apoptotic death of tumor cells in vivo. Structural studies of Fab41.4 were
      performed to gain insight into the mechanism of action of this potentially
      therapeutic antibody. The optimal conditions for crystallization of Fab41.4 were
      determined. Crystals were needle-like in appearance, displayed C2 space-group
      symmetry and diffracted to a resolution of 1.6 A. The unit-cell parameters were
      determined to be a = 186.64, b = 40.22, c = 55.58 A, alpha = gamma = 90, beta =
      96.93 degrees. The data set was 97.7% complete. Molecular replacement was
      performed, resulting in an R value of 44.6%.

PMID- 11223534
TI  - Crystallization and initial X-ray diffraction analysis of human pyruvate
      dehydrogenase.
AB  - Human pyruvate dehydrogenase (E1) is a component enzyme of the pyruvate
      dehydrogenase complex. The enzyme catalyzes the irreversible decarboxylation of
      pyruvic acid and the rate-limiting reductive acetylation of the lipoyl moiety
      linked to the dihydrolipoamide acetyltransferase component of the pyruvate
      dehydrogenase complex. E1 is an alpha(2)beta(2) tetramer ( approximately 154
      kDa). Crystals of this recombinant enzyme have been grown in polyethylene glycol
      3350 using a vapor-diffusion method at 295 K. The crystals are characterized as
      orthorhombic, space group P2(1)2(1)2(1), with unit-cell parameters a = 64.2, b =
      126.9, c = 190.2 A. Crystals diffracted to a minimum d spacing of 2.5 A. The
      asymmetric unit contains one alpha(2)beta(2) tetrameric E1 assembly; self
      rotation function analysis showed a pseudo-twofold symmetry relating the two
      alphabeta dimers.

PMID- 11223535
TI  - Crystallization and secondary-structure determination of a protein of the
      Lrp/AsnC family from a hyperthermophilic archaeon.
AB  - A protein belonging to the Lrp/AsnC transcription-factor family, pot1216151, from
      the hyperthermophilic archaeon Pyrococcus sp. OT3 was crystallized. In
      Escherichia coli, leucine-responsive protein (Lrp) and AsnC regulate a number of
      metabolic genes. The crystals of pot1216151 diffracted to 2.3 A using a
      conventional X-ray source and to 1.8 A using a synchrotron-radiation source. The
      space group was identified to be P3(1)21 or P3(2)21, with unit-cell parameters a
      = b = 96.9, c = 98.5 A. In combination with diffraction data obtained from
      K(2)[Pt(CN)(6)] and K(AuCl(4)) derivatives, an electron-density map was
      calculated at a resolution of 3.0 A. Four monomers were identified in the
      asymmetric unit, with four beta-strands and two alpha-helices in each monomer.

PMID- 11223536
TI  - A distinct binding mode of a hydroxyethylamine isostere inhibitor of HIV-1
      protease.
AB  - Crystallization conditions for an HIV-1 protease-inhibitor complex were optimized
      to produce crystals suitable for X-ray diffraction experiments. The X-ray
      structure of the HIV-1 protease complex was solved and refined at 3.1 A
      resolution. In contrast to Saquinavir, the mimetic hydroxy group of the inhibitor
      Boc-Phe-Psi[(S)-CH(OH)CH(2)NH]-Phe-Glu-Phe-NH(2) is placed asymmetrically with
      respect to the non-crystallographic twofold axis of the protease dimer so that
      hydrogen bonds between the amino group of the inhibitor and the catalytic
      aspartates can be formed. The inhibitor binds in the centre of the active site by
      a compact network of hydrogen bonds to Gly27, Gly127, Asp25, Asp125 and via the
      buried water molecule W301 to Ile50 and Ile150.

PMID- 11223538
TI  - Lack of effect of soy isoflavone on thyroid hyperplasia in rats receiving an
      iodine-deficient diet.
AB  - We have reported a dramatic synergism between soy intake and iodine deficiency
      regarding induction of thyroid hyperplasia in rats. Because isoflavones are
      active constituents of soybeans, in the present study, their possible
      contribution was examined. Female F344 rats were divided into 8 groups, exposed
      to diet containing a 0.2% soy isoflavone mixture (SI), 0.2% SI + iodine
      deficiency (ID), 0.04% SI, 0.04% SI + ID, 20% defatted soybean (DS) alone, 20% DS
      + ID, ID alone or basal diet alone for 5 weeks. Thyroid weight was not influenced
      by SI, but was increased by the ID and DS diets with a further significant
      increment in the DS + ID group (P < 0.01). Compared to the control value, serum
      T(4) was significantly (P < 0.01) increased by 20% DS alone and decreased in all
      groups given the ID treatment (P < 0.001). Serum thyroid stimulating hormone
      (TSH) level was increased by ID, and further enhanced by DS (P < 0.01) but not
      SI. Histopathologically, diffuse hypertrophy and / or hyperplasia of thyroid
      follicles were observed in the ID-treated groups, the severity being enhanced by
      DS but not SI. Proliferating cell nuclear antigen labeling indices (%) were
      elevated in the ID diet groups and again enhanced by DS, but not SI. These
      results thus suggest that isoflavones may not be involved in the mechanisms
      underlying the synergistic goitrogenic effect of soybean with iodine deficiency.

PMID- 11223539
TI  - Hexosaminidase-altered aberrant crypts, carrying decreased hexosaminidase alpha
      and beta subunit mRNAs, in colon of 1,2-dimethylhydrazine-treated rats.
AB  - Aberrant crypt foci (ACF), consisting of morphologically irregular crypts, are
      thought to be precancerous lesions for colon cancers. For their molecular
      analysis, it is necessary to avoid contamination with adjacent normal crypts and
      stromal cells. Decreased hexosaminidase activity in ACF, which has been
      histochemically demonstrated, was used in the present study to classify isolated
      crypts in combination with morphological changes. The length, rim diameter, and
      width (average SD, microm) of hexosaminidase-positive (Hex + ) crypts were 238.6
      +/- 40.4, 89.5 +/- 22.9, and 57.6 +/- 14.0, respectively. For hexosaminidase
      negative (Hex - ) crypts, the values were 314.4 +/- 77.8, 140.3 +/- 45.7, and
      97.3 +/- 34.7, the width being 1.69 times greater (P < 0.0001). Crypts wider than
      115 microm (approximately 2 times the average size of Hex + crypts) were all from
      ACF, judging from hexosaminidase staining. To analyze transcription levels of Hex
      alpha and beta subunits (Hexa and Hexb, respectively), real-time relative
      quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis
      was performed using the LightCycler system. In aberrant crypts, both Hexa and
      Hexb were significantly down-regulated to 0.266 (P < 0.002) and 0.131 (P < 0.001)
      units, respectively, compared with those in morphologically normal crypts, with
      beta-actin as the internal standard. This decrease could be a molecular marker
      for precancerous enzyme-altered ACF.

PMID- 11223540
TI  - Mutations of p53 in morphologically non-neoplastic mucosa of long-standing
      ulcerative colitis.
AB  - Two cases of ulcerative colitis (UC)-associated carcinoma or dysplasia and
      morphologically non-neoplastic mucosa with p53 protein overexpression (MNNM
      p53OE) were selected. DNA was extracted from the paraffin blocks of these lesions
      and exons 5 - 8 of the p53 gene were analyzed by PCR and direct sequencing. In
      addition, mutations in K-ras codon 12 were analyzed by PCR-RFLP methods. MNNM
      p53OE was located surrounding and adjoining a coexisting carcinoma and / or
      dysplasia. A p53 mutation was detected in 12 / 22 (54.5%) MNNM-p53OE samples, 4 /
      8 (50%) dysplasia samples and 8 / 8 (100%) carcinoma samples. The p53 mutations
      detected in MNNM-p53OE were identical to those demonstrated in the adjoining
      carcinoma and / or dysplasia. No K-ras codon 12 mutation was detected in any of
      the samples. These results indicate that MNNM-p53OE may share an identical clonal
      linkage with a coexisting carcinoma and / or dysplasia, and may be an initial and
      submorphological form of UC-associated neoplasia. Recognition of MNNM-p53OE in
      biopsy specimens may help to identify patients with UC at risk of developing
      colorectal carcinoma.

PMID- 11223541
TI  - Molecular significance of excess body weight in postmenopausal breast cancer
      patients, in relation to expression of insulin-like growth factor I receptor and
      insulin-like growth factor II genes.
AB  - A number of epidemiological and clinical studies have revealed that excess body
      weight increases the risk of postmenopausal breast cancer and also adversely
      affects subsequent malignant progression. To elucidate the molecular mechanisms
      underlying these observations, we examined mRNA expression of various genes in
      normal (non-cancerous) mammary gland and cancer tissue of Japanese patients with
      primary breast cancer, in association with their body mass index (BMI). On the
      basis of analysis of 106 breast cancer patients, we found that mRNA expression of
      insulin-like growth factor I receptor (IGF-IR) and insulin-like growth factor II
      (IGF-II) in the normal mammary gland showed a significant and positive
      association with increased BMI among postmenopausal patients. Furthermore, the
      positive association of increased BMI with IGF-IR mRNA expression was also found
      in postmenopausal breast cancer tissue, while this association was not observed
      among premenopausal patients. In addition, increased mRNA expression of cyclin D1
      and bcl-2 was observed in association with increased mRNA levels of IGF-IR among
      the patients regardless of menopausal status. These findings suggest that the
      molecular consequence of the increased BMI is the increased expression of IGF-II
      and IGF-IR, resulting in development of postmenopausal breast cancer and its
      progression mediated through modulation of the cell cycle and apoptosis.

PMID- 11223542
TI  - Fusion of a sequence from HEI10 (14q11) to the HMGIC gene at 12q15 in a uterine
      leiomyoma.
AB  - Uterine leiomyoma, a benign smooth-muscle tumor of the myometrium, is the most
      commonly encountered neoplasm in women of reproductive age. Band q15 of
      chromosome 12 is often rearranged in benign mesenchymal tumors such as uterine
      leiomyomas, and the HMGIC gene, encoding a protein of the high-mobility-group
      (HMG), is present in that region. Using 3' rapid amplification of cDNA ends
      (3'RACE) experiments, we isolated an ectopic sequence that was fused to HMGIC in
      a uterine leiomyoma. Cloning of the fusion cDNA identified a gene termed rising
      dbl quote, left (low)homo sapiens enhancer of invasion 10" (HEI10) as the fusion
      partner. Radiation hybrid mapping revealed that the normal location of HEI10 is
      at 14q11. In the fusion transcript the first two exons of the HMGIC gene, which
      encode DNA-binding domains, were fused to the 3' portion of the HEI10 gene. This
      rearrangement implicates HMGIC in the tumorigenesis of uterine leiomyoma, and
      suggests that its fusion HMGIC product may play a role in mesenchymal
      differentiation.

PMID- 11223543
TI  - Structure, expression and chromosome mapping of MLZE, a novel gene which is
      preferentially expressed in metastatic melanoma cells.
AB  - We isolated a novel gene, termed MLZE, from a B16-BL6 cDNA library after
      subtraction of B16-F10 mRNA. Expression levels of mouse MLZE (mMLZE) increased in
      accordance with metastatic ability of B16 melanoma sublines. Human homolog of
      mMlze (hMlze) contained one leucine zipper structure and two potential nuclear
      localizing signals. Northern blot analysis of multiple human tissues showed that
      hMLZE was expressed primarily in trachea and spleen. We mapped the hMLZE gene (by
      fluorescence in situ hybridization) to 8q24.1 - 2, which contains the c-myc gene
      and is often amplified in malignant melanoma. Immunohistochemistry revealed that
      the number of hMlze-positive cases was significantly larger in Clark levels III,
      IV and V melanomas (6 / 11 = 55%) than in Clark levels I and II melanomas (2 / 15
      = 13%). In two cases of hMlze-positive melanomas, the strength of hMlze staining
      increased substantially in the deep component of the tumor. Considering that
      melanomas above Clark level II are more metastatic than those below Clark level
      III, these findings suggested that MLZE is one of the genes whose expression is
      upregulated during the course of acquisition of metastatic potential in melanoma
      cells.

PMID- 11223544
TI  - Signal transduction pathways through TRK-A and TRK-B receptors in human
      neuroblastoma cells.
AB  - Little is known about the signal transduction pathways of TRK family receptors in
      neuroblastoma (NB) cells. In this study, an NB cell line, designated MP-N-TS, was
      established from an adrenal tumor taken from a 2-year-old boy. This cell line
      expressed both TRK-A and TRK-B receptors, which is rare in a single NB cell line.
      Therefore, the MP-N-TS cell line was used to determine whether the signal
      transduction through these constitutive receptors is functional. Three
      neurotrophins, nerve growth factor (NGF), brain-derived neurotrophic factor
      (BDNF) and neurotrophin-4 / 5 (NT-4 / 5), induced tyrosine phosphorylation of
      panTRK, and BDNF and NT-4 / 5 induced tyrosine phosphorylation of TRK-B. Tyrosine
      phosphorylation of panTRK and / or TRK-B by the neurotrophins was inhibited in
      the presence of a tyrosine kinase inhibitor K252a. Tyrosine phosphorylation of
      Src homologous and collagen (Shc), extracellular signal-regulated kinase (ERK)-1
      and ERK-2, and phospholipase C-gamma1 (PLC-gamma1) was increased by the three
      neurotrophins and the increase was inhibited in the presence of K252a. Activation
      of Ras, detected as the GTP-bound form of Ras, was induced by the three
      neurotrophins. The neurotrophins did not modulate the expressions of TRK-A or TRK
      B mRNA, but they did induce the expression of c-fos mRNA. Exogenous NGF induced
      weak neurite outgrowth, whereas exogenous BDNF and NT-4 / 5 induced distinct
      neurite outgrowth. Exogenous BDNF and NT-4 / 5 increased the number of viable
      cells, while NGF did not. Our results demonstrate that the signal transduction
      pathways through TRK-A and TRK-B in MP-N-TS cells are functional and similar, and
      the main downstream signaling pathways from the three neurotrophins are mitogen
      activated protein kinase (MAPK) cascades through Shc, activated Ras, ERK-1 and
      ERK-2, and the transduction pathway through PLC-gamma1. Further, BDNF and NT-4 /
      5 increased cell viability. The MP-N-TS cell line should be useful for clarifying
      the TRK-A and TRK-B signaling pathways responsible for the different prognoses in
      patients with NB.

PMID- 11223545
TI  - Heterogeneity of p53 mutational status in intramucosal carcinoma of the
      colorectum.
AB  - The aim of this study was to elucidate whether or not p53 genetic heterogeneity
      would occur while colorectal carcinoma was limited to the mucosa. Eight cases of
      endoscopically resected colorectal intramucosal carcinomas were analyzed to
      determine the p53 gene sequence (exons 5 to 8). Six out of 8 cases showed p53
      gene mutations, and in all of them, the mutational status was heterogeneous. In 4
      cases, mutated codons were heterogeneous as well. These data indicate that p53
      gene alterations in colorectal carcinomas occur and diverge at the stage of
      intramucosal carcinoma, supporting our previously proposed hypothesis that
      colorectal carcinomas can be composed of various subclones as regards p53 gene
      mutation, while the carcinoma is limited to the mucosa, and one of these
      subclones commences invasion to the submucosa after clonal selection, thus
      generating a monoclonal invasive carcinoma.

PMID- 11223546
TI  - Expression of MAGE-B genes in esophageal squamous cell carcinoma.
AB  - The MAGE-B (MAGE-B1, -B2, -B3, and -B4) genes share strong homology with the MAGE
      A gene family. MAGE-B1 and -B2 encode common tumor-specific peptide antigens.
      There is, however, still very little information about the expression of these
      genes in human gastro-intestinal carcinomas. We investigated the expression of
      MAGE-B1 and -B2 genes in 29 cell lines and 53 clinical tumor samples of
      esophageal squamous cell carcinoma by reverse transcription polymerase chain
      reaction (RT-PCR). MAGE-B1 and -B2 gene transcripts were detected by RT-PCR in 1
      (3%) and 6 (21%) cell lines, and in 9 (17%) and 17 (32%) clinical samples,
      respectively. Among them, 7 / 29 (24%) cell lines and 19 / 53 (36%) clinical
      samples expressed at least either MAGE-B1 or -B2. A significant correlation was
      found between negative MAGE-B gene expression and vascular invasion (P = 0.008).
      In 45 out of 53 esophageal carcinoma RNA samples, the MAGE-A1, -A2, and -A3 genes
      were detected in 27 (60%), 23 (51%), and 30 (67%) samples, respectively, while
      the MAGE-B genes were detected in 18 (40%) samples. The frequency of MAGE-B gene
      expression in esophageal carcinoma was relatively higher than that observed for
      gastric or colorectal carcinomas (12% and 2%, respectively). Therefore, the MAGE
      B genes could be used as targets in specific immunotherapy of esophageal squamous
      cell carcinomas.

PMID- 11223547
TI  - Establishment of cell lines with high- and low-metastatic potential from PC-14
      human lung adenocarcinoma.
AB  - This article reports the establishment of variant cell lines with high and low
      metastatic potential by repeated selection and the dilution plating technique.
      Five clones with high metastatic potential, Lu-2, Lu-7, Lu-4, Lu-1 and Lu-5, and
      four clones with low metastatic potential, 3S, 7S, 8S and 13S, were established
      from PC-14 human lung adenocarcinoma. The high-metastatic cell lines produced
      enhanced lung metastases, but the low-metastatic cell lines did not produce lung
      metastasis by injection into the tail vein of 5-week-old BALB / c nude mice. The
      high-metastatic cell lines produced enhanced tumors on both visceral and parietal
      pleurae, and enhanced metastases to the mediastinum and contralateral pleural
      cavity. The low-metastatic cell lines produced reduced tumors on both visceral
      and parietal pleurae and reduced metastases to the mediastinum and contralateral
      pleural cavity after injection into the left preceral cavity of the nude mice.
      When the nine variant cell lines and original PC-14 cells were embedded in
      collagen gels, the PC-14 cells and the low-metastatic cell lines gave rise to
      colonies with a dendritic morphology, and cells were tightly associated. The high
      metastatic cell lines were more loosely associated and scattered into three
      dimensional colonies. These nine cloned cell lines originated from heterogeneous
      populations of the parental PC-14 cells should be useful tools for studying the
      process of metastasis of lung cancer.

PMID- 11223548
TI  - Sole expression of laminin gamma 2 chain in invading tumor cells and its
      association with stromal fibrosis in lung adenocarcinomas.
AB  - Laminin-5 (LN-5), an important basement membrane (BM) protein consisting of
      laminin alpha3, beta3 and gamma 2 chains, has been suggested to be involved in
      tumor cell invasion and tissue repair. In this study, the distribution of the LN
      5 subunits in atypical adenomatous hyperplasia (AAH) and different types of
      adenocarcinomas of the lung was examined by immunohistochemical analysis. In AAH
      and non-sclerosing, well-differentiated adenocarcinomas, the LN gamma 2 chain was
      frequently detected along with the continuous BMs. These BMs were also positive
      for both LN alpha3 and beta3 chains, suggesting that LN-5 had been deposited. In
      contrast, the cytoplasmic staining for the LN gamma 2 chain was frequently
      observed in tumor cells of sclerosing, well-differentiated adenocarcinomas, as
      well as of moderately and poorly differentiated adenocarcinomas, without any
      evidence of co-expression of the LN alpha3 and beta3 chains. This staining
      pattern of the LN gamma 2 chain was prominent in carcinoma cells invading into
      interstitial stroma and was associated with the formation of a central scar in
      the tumor tissues. These results suggest that the LN gamma 2 chain monomer could
      be an important indicator of progression of lung adenocarcinoma.

PMID- 11223549
TI  - Different susceptibilities of postmitotic checkpoint-proficient and -deficient
      Balb / 3T3 cells to ICRF-193, a catalytic inhibitor of DNA topoisomerase II.
AB  - Two distinct types of Balb / 3T3 cells were isolated which exhibit either 4 N DNA
      or both 4 N and 8 N DNA after exposure to colcemid for 48 h. They were found to
      differ with respect to the postmitotic checkpoint, but not the mitotic
      checkpoint. Firstly, the checkpoint-proficient and -deficient cells exhibited the
      same accumulation and subsequent decrease in the number of mitotic cells
      following exposure to microtubule inhibitors. Secondly, after exit from abnormal
      mitosis in the presence of ICRF (Imperial Cancer Research Fund)-193, the
      checkpoint-proficient cells were arrested in the next cycle G1, while the
      checkpoint-deficient cells progressed into S and G2 phase. When either mitotic or
      asynchronous cells were exposed to ICRF-193, the checkpoint-proficient cells
      proved more sensitive to the cytotoxic effect of this agent than the checkpoint
      deficient cells. The different susceptibilities of the two types of cells to ICRF
      193 were not caused by variation in topoisomerase (topo) II function since both
      the biochemical activity of this enzyme and chromosome segregation were inhibited
      by similar concentrations of ICRF-193 in both checkpoint-proficient and 
      deficient cells. We propose that the inhibition of chromosome segregation by ICRF
      193 is monitored by the next G1 checkpoint, resulting in an irreversible G1 block
      in the case of postmitotic checkpoint-proficient cells. As the checkpoint
      deficient cells can escape this G1 block, these cells have an increased survival
      capacity. In summary, ICRF-193 may prove to be a very useful drug for examination
      of the postmitotic checkpoint.

PMID- 11223550
TI  - Examination of in vitro chemosensitivity test using collagen gel droplet culture
      method with colorimetric endpoint quantification.
AB  - To develop a simpler method of performing the collagen gel droplet-embedded
      culture drug sensitivity test (CD-DST), we examined the introduction of
      colorimetric quantitative determination of images for evaluation of anticancer
      effect against cancer cells alone in the presence of fibroblasts, based on
      differences in proliferative morphology and stainability with neutral red of
      cells within collagen gel drops determined using a video-microscope and NIH Image
      software. In examinations using a human cancer cell line and a fibroblast cell
      line, a high degree of linearity between number of cancer cells and image-optical
      density was found within the range of 10(2) - 10( 6) cells / droplet (r (2) =
      0.933). Using NIH Image, fibroblast cells could be eliminated at a cut-off value
      of 128, and an immunocytochemical method demonstrated that the cells eliminated
      from the image were indeed fibroblasts, and those remaining were cancer cells. CD
      DST was carried out with mixtures of cancer cells with fibroblasts at various
      ratios, and the feasibility of evaluating anticancer activity in cancer cells
      alone with no effect of fibroblasts at any mixing ratio was confirmed. In
      addition, for CD-DST of primary cell cultures of human lung cancers collected at
      the time of surgery, a high correlation between results obtained with the volume
      supplementation method, a current cell quantification method, and those with the
      imaging colorimetric quantification method was obtained (r = 0.933). These
      results indicate that introduction of imaging colorimetric quantification
      utilizing NIH Image makes CD-DST a quick and simple method that should be highly
      useful for clinical chemosensitivity testing using primary cell cultures of human
      cancers.

PMID- 11223551
TI  - Involvement of the multidrug resistance protein 3 in drug sensitivity and its
      expression in human glioma.
AB  - The multidrug resistance protein (MRP) family belongs to the ATP-binding cassette
      superfamily (ABC) of transporters, which are involved in ATP-dependent transport
      of hydrophobic compounds. One of the MRP family, MRP1, is partially associated
      with the multidrug resistance phenotype in brain tumors. In this study, we asked
      whether another MRP family gene, MRP3, could affect drug sensitivity to
      anticancer agents in human glioma cell lines and clinical glioma specimens. We
      first produced two antisense transfectants by introduction of antisense MRP3 cDNA
      into the glioma cell line NHG2, which endogenously expresses MRP3. The two MRP3
      antisense transfectants showed 2- to 5-fold increases in drug sensitivity to
      etoposide and cisplatin compared with NHG2 cells, but their sensitivity to
      vincristine or nitrosourea was not changed. Two MRP3 cDNA sense transfectants of
      pig kidney cell lines showed 4- to 6-fold drug resistance to etoposide, but only
      1.4- to 1.5-fold to cisplatin. We next compared the mRNA levels of four ABC
      transporters, multidrug resistance 1 (MDR1), MRP1, MRP2 and MRP3 in clinical
      samples, including 34 patients with gliomas, by quantitative RT-PCR analysis. In
      some of the clinical samples, increased expression of MRP1 and MRP3 was apparent
      in malignant gliomas. In situ hybridization revealed that glioma cells were
      stained with MRP3 probe. MRP3 may modulate drug sensitivity to certain anticancer
      agents in human gliomas.

PMID- 11223552
TI  - Phase I study of intravenous PSC-833 and doxorubicin: reversal of multidrug
      resistance.
AB  - PSC-833 reverses multidrug resistance by P-glycoprotein at concentrations < or =
      1000 ng / ml. A phase I study of PSC-833 and doxorubicin was conducted to
      determine the maximum tolerated dose and to investigate pharmacokinetics. PSC-833
      was intravenously infused as a 2-h loading dose (LD) and a subsequent 24-h
      continuous dose (CD). Doxorubicin was infused over 5 min, 1 h after the LD. The
      starting dose was 1 mg / kg for both LD and CD with 30 mg / m(2) doxorubicin;
      these dosages were increased to 2 and 10 mg / kg and 50 mg / m(2), respectively.
      Thirty-one patients were treated. Nausea / vomiting was controllable with
      granisetron and dexamethasone. Neutropenia and ataxia were dose limiting. Steady
      state concentrations of PSC-833 > 1000 ng / ml were achieved at a 2 mg / kg LD
      and a 10 mg / kg CD. Ex-vivo bioassay revealed that activity in serum for
      reversing multidrug resistance was achieved in all patients; IC(50) of P
      glycoprotein expressing 8226 / Dox(6) in patients' serum was decreased from 5.9
      to 1.3 microg / ml (P < 0.0001) by PSC-833 administration. Doxorubicin clearance
      was 24.3 +/- 13.7 (mean +/- SD) liter / h/m(2), which was lower than the 49.0 +/-
      16.9 liter / h/m(2) without PSC-833 (P < 0.0001). The relationship between
      doxorubicin exposure and neutropenia did not differ between patients treated and
      not treated with PSC-833. The recommended phase II dose of PSC-833 was 2 and 10
      mg / kg for LD and CD, respectively, which achieved a sufficient concentration in
      serum to reverse drug resistance, as confirmed by bioassay. The dose of
      doxorubicin should be reduced to 40 mg / m(2), not because of the pharmacodynamic
      interaction between PSC-833 and doxorubicin affecting hematopoiesis, but because
      of pharmacokinetic interaction.

PMID- 11223553
TI  - Pharmacodynamic modeling of the entire time course of leukopenia after a 3-hour
      infusion of paclitaxel.
AB  - The entire time course of leukopenia after anticancer treatment is clinically
      more relevant than a singly measured nadir count. In order to identify factors
      associated with neutropenic fever, a mechanistic pharmacodynamic model with two
      compartments corresponding to leukocytes in bone marrow and peripheral blood was
      applied to describe the time course of leukopenia. Seventeen patients with breast
      cancer were treated with 210 mg / m(2) of paclitaxel infused over 3 h as a single
      agent in a phase II study. Adequate fitting of the time course of leukopenia was
      achieved in all patients, and time-dependent parameters, including the time
      period during which leukocyte counts remained below 2000 / microl and the area
      between the curve for time versus leukocyte counts and the line of a leukocyte
      count of 2000 / microl (A < 2000), were calculated in each patient. Leukopenia
      was not significantly correlated with pharmacokinetic parameters, including time
      above a threshold concentration or the area under the time-concentration curve. A
      negative correlation between age and the sensitivity parameter of the
      pharmacodynamic model was observed (r (2) = 0.21, P = 0.07). Patients who
      experienced neutropenic fever had a larger A < 2000 than patients who did not
      experience fever (4512 vs. 6 days / microl, P = 0.05), but fever was not
      significantly related to any pharmacokinetic parameter or the leukocyte nadir
      count. Febrile episodes were better associated with the time course of leukopenia
      than the singly measured nadir count, and the pharmacodynamic model presents a
      novel platform to analyze the entire time course of leukopenia.

PMID- 11223555
TI  - Histologic findings in a series of 1,540 corneal allografts.
AB  - We present a series of 1,540 corneal allografts studied since 1982. Corneal edema
      was the major lesion in 439 corneal specimens (28.4%). Keratitis was the largest
      group with 378 cases (24.5%), including 134 cases of corneal scarring (8.7%).
      There were 113 cases of herpes simplex virus keratitis (7.3%), mostly of the
      disciform stromal type, and 60 cases of non herpetic interstitial keratitis
      (3.9%), 44 of superficial keratitis (2.8%) and 10 of ulcerative keratitis (0.6%).
      Among the 17 other cases (1.1%), there were 3 of fungal keratitis, 2 syphilitic
      keratitis and one case of acanthamoebic keratitis. The third group was formed by
      corneal dystrophies with 376 cases (24.4%). There were 192 keratoconus (12.5%),
      121 Fuchs' dystrophies (7.9%), 28 calcific band keratopathies (1.8%), 18 had
      corneal dystrophies with amyloid deposits and 16 did not. There were 169 regrafts
      (11%) and 135 traumatic lesions (8,8%). Among the 43 miscellaneous cases (2,8%),
      there were 22 cases with previous refractive eye surgery, one corneal myxoma, 5
      cases of dysplasia, 5 pterigia, 3 sclerocornea, one fish-eye disease, one floppy
      eyelid syndrome and 5 unclassifiable cases. The mechanisms of these lesions are
      mainly related to an autoimmune disease in most cases of herpes keratitis. Some
      rare forms of corneal dystrophies contain amyloid deposits produced by an
      abnormal kerato-epithelin. Cases of graft failure are not particulary frequent,
      due to the avascularity of the cornea and its particular immune status.

PMID- 11223556
TI  - [HBME-1 immunostaining in thyroid pathology].
AB  - The aim of this study was to evaluate wether HBME-1 immunohistochemical analysis
      can reliably differentiate benign thyroid lesions from thyroid carcinomas. Fifty
      benign and 87 malignant lesions were analyzed. All papillary carcinomas (67/67)
      were HBME-1 positive, as well as 14 of 20 follicular well-differentiated
      carcinomas and 13 of 29 atypical follicular adenomas and 4 out of 21 goiters were
      weakly and focally positive. HBME-1 highlighted micronests of papillary
      carcinomas. The reactivity of HBME-1 in the tall-cell variant of papillary
      carcinomas was apical and stronger than in classical papillary carcinomas.
      Positive HBME-1 immunostaining is in support of the diagnosis of the follicular
      variant of papillary carcinoma and highlights micropapillary carcinomas. HBME-1
      may be of additional value in the diagnosis of thyroid malignancy.

PMID- 11223557
TI  - [Medical demography: the portrait of pathologic anatomy and cytology].
AB  - Assessment of care supply in terms of medical labor force is difficult because of
      the disparity of available data. Using the medical specialty of pathology as an
      example, we present for the first time a demographic analysis based on the
      confrontation of main data sources. This study underlines some of the structural
      and dynamic problems which threaten the demographic stability of the specialty.
      The public service suffers from a lack of practitioners, especially in regional
      hospitals. Whereas one third of French pathologists work in the larger hospitals
      around Paris, in some other regions private services constitute the main
      component of the supply. Projections based on the aging phenomenon and a
      reduction in entry indicate a future problem in the renewal of generations of
      pathologists. The consequences of this programmed decrease in the number of
      French pathologists will be further exacerbated by the movement of the sex ratio
      in favor of women.

PMID- 11223558
TI  - [Formaldehyde fixation in the third millennium].
AB  - This review deals with the general principles and problems of formaldehyde
      fixation. After a short description of 1) formaldehyde methods of production, 2)
      chemical properties of formaldehyde solution, and 3) kinetic of formaldehyde
      binding in tissue, formaldehyde reactivity with the tissue biopolymers, proteins
      and cucleic acids mainly, are described. How formaldehyde fixation of tissues
      adversely affects the reactivity of cellular proteins with their respective
      specific antibody and the ways the most commonly used retrieval techniques in
      immunohistochemistry act are, thereafter, discussed. Finally, concerns that need
      to be dealt with when formalin-fixed specimens are used for genomic analysis and
      studies of DNA expression are highlighted.

PMID- 11223559
TI  - [Epithelioid leiomyosarcoma of the uterine cervix. Report of a case].
AB  - We report a case of an epithelioid leiomyosarcoma of the uterine cervix in a 42
      year-old woman. This is a very rare tumor. Usually, the presenting symptoms are
      vaginal bleeding and abdominal pain. Two problems have to be solved by the
      microscopy: to prove the smooth muscle differentiation of the tumor and to assert
      the malignancy. Surgery remains the basis of therapy. Prognosis is poor.

PMID- 11223561
TI  - [Anaplastic temporal ganglioglioma with spinal metastasis].
AB  - We report the case of a 26-year-old male who was operated on after an acute
      episode complicating a long history of seizures. The resected temporal lesion was
      an anaplastic ganglioglioma. Ganglioglioma is a tumor of children and young
      adults, characterized by two cell components, neuronal and glial. It is usually a
      benign lesion. The present case is remarkable in several aspects. Hemorrhage led
      to the discovery of a supra-tentorial tumour. Microscopic examination revealed
      anaplastic foci in an otherwise typical lesion. There was a long past medical
      history but outcome was rapidly unfavorable after surgical resection and
      associated with dissemination along the spinal cord.

PMID- 11223560
TI  - [Alveolar rhabdomyosarcoma: apropos of a rare location].
AB  - Rhabdomyosarcoma is a soft tissue tumor of striated muscle origin. It is observed
      mainly in children and adolescents. Rhabdomyosarcoma predominantly occurs in
      three regions: head and neck, genito-urinary tract and retroperitoneum, and upper
      and lower extremities. We report a case of primary alveolar rhabdomyosarcoma of
      the mesentery occurring in a 68-year-old man. Rhabdomyosarcomas can be diagnosed
      on microscopic findings and immunohistochemical features. Cytogenetic findings
      can be helpful in the diagnosis.

PMID- 11223562
TI  - [Primary breast MALT lymphoma : apropos of one case].
AB  - A 46-year-old patient was referred for a right mammary nodule associated with a
      chronic mastopathy. Cytological examination suggested an inflammatory process but
      frozen sections concluded to carcinoma with lymphoid stroma. Histological
      examination found characteristic features of MALT lymphoma: reactive lymphoid
      follicles, lymphoplasmocytoid lymphoid proliferation and lymphoepithelial
      lesions. Immunohistochemistry and in situ hybridation revealed a monotypic IgGk
      immunoglobulin. Molecular biology techniques found a rearrangement of IgH locus.
      Lymphocytic perigalactophoritis was found in the remaining breast tissue. After
      33 months, no tumoral recurrence occurred. Primary MALT lymphoma of the breast is
      exceptional and its histogenesis is unclear. The role of pre-existent
      inflammatory lesions in the genesis of this tumour is not established. Our
      observation illustrates the diagnostic difficulty and the usefulness of
      complementary techniques in this diagnosis. The existence of inflammation close
      to tumour is interesting to emphasize.

PMID- 11223563
TI  - [Apropos of 1 case of paratesticular papillary serous cystadenocarcinoma].
AB  - The occurrence within the testis or paratesticular tissue of serous tumors,
      similar to ovarian tumors, is rare. This article reports a primary serous
      paratesticular cystadenocarcinoma in a 39 year-old man. From data of the
      literature, we offer guidelines for diagnosis, histogenesis and treatment of this
      rare tumor.

PMID- 11223564
TI  - [Biphasic sarcomatoid carcinoma of the prostate].
AB  - Sarcomatoid carcinoma of the prostate is a rare aggressive tumor, characterized
      by an intimate admixture of two malignant epithelial and sarcomatoid components.
      We report the case of a prostate tumour reputed to have a poor outcome, in a 59
      year-old man. The radical prostatectomy specimen was completely involved. There
      were no signs of recurrence or metastasis after 15 months of follow up. The serum
      PSA values before and after chirurgical treatment were normal. The definition of
      this tumour as its histogenesis and prognosis is discussed.

PMID- 11223565
TI  - [Parapharyngeal synovial sarcoma].
AB  - A parapharyngeal biphasic synovial sarcoma arising in a 38-year-old man is
      reported. The rarity of this tumor in the head and neck and its multitude of
      histopathologic features are responsible for frequent initial misdiagnosis. The
      purpose of this report is to highlight the differential diagnosis with other
      cervical tumors.

PMID- 11223566
TI  - [Congenital fetal neuroblastoma].
AB  - Neuroblastoma are pediatric tumors of neural crest origin, most often localized
      in adrenal glands and infrequently congenital. We report two fetal cases found at
      autopsy, performed at 24 and 28 weeks of gestation, respectively. The 24 week old
      fetus did not show any malformation; systematic histological analysis found
      neuroblastoma cells in both the adrenal glands and the retroperitoneal fat
      tissue. The 28 week old fetus was hydropic and exhibited a nodule (3 cm) in the
      posterior mediastinum, next to the thoracic spinal cord. This tumor responded to
      a neuroblastoma associated with small metastatic foci in the adrenal glands, the
      liver and the frontal brain cortex. The placenta was abnormally heavy and showed
      hemorrhagic and necrotic areas. Microscopically plugged clumps of neuroblastoma
      cells were found inside fetal vessels. Immunohistochemistry was employed in both
      cases and the cells showed immunoreactivity for NSE, NB 84, chromogranin,
      synaptophysin and neurofilaments, while desmin, MIC 2, and protein S-100 were
      negative. Congenital neuroblastomas are rare and, to our knowledge this is the
      thirteenth report of congenital neuroblastoma associated with placental
      metastasis.

PMID- 11223567
TI  - [A composite bone tumor].

PMID- 11223568
TI  - [Nodule of the fallopian tube].

PMID- 11223569
TI  - [A gastric tumor].

PMID- 11223570
TI  - [A vascular tumefaction].

PMID- 11223571
TI  - [An intratesticular nodule].

PMID- 11223572
TI  - [Resin polymerizing at low temperatures: II. Histochemistry, electron microscopy
      and immunomarkers].
AB  - For pathologists, tissu processing and analysis require good preservation of both
      the shape (morphology) and the content of the cells (antigens, nucleic acids).
      Low temperature embedding resins are the only inclusion substrate which allows
      both a fine morphological analysis and good preservation of antigens and nucleic
      acids. Automatic the technical processes and simplified protocols now allow the
      introduction of low temperature embedding resins in diagnostic procedures.

PMID- 11223574
TI  - [The anatomo-pathologist is not a retriever!].

PMID- 11223573
TI  - [Papillary cystadenoma of the epididymis revealing von Hippel-Lindau disease].

PMID- 11223575
TI  - [Mitochondria: recent pathophysiological discoveries and new therapeutic
      perspectives].
AB  - Until about a decade ago, few researchers in clinical or evolutionary biology
      paid much attention to mitochondria. But over the years, as technological
      advances in molecular biology made nuclear functions more accessible to them,
      interest in mitochondria began to revive. First, geneticists started tracing
      certain rare inherited disorders to mutations in the mitochondria's circular
      genome. More recently, other researchers have speculated that mitochondria might
      contribute to aging, either by releasing tissue-damaging reactive oxygen
      molecules or by impairing and depriving the cell of the energy it needs to
      function. One the most important recent developments has been the recognition
      that mitochondria play a central role in the regulation of programmed cell death,
      or apoptosis. Now, we know that mitochondria play a decisive role in life-death
      decisions for the cell and may choose between the apoptotic and necrotic
      pathways. Mitochondria can trigger cell death in a number of ways: by disrupting
      electron transport and energy metabolism, by activating the mitochondrial
      permeability transition, by releasing and/or activating proteins that mediate
      apoptosis. Any or all of these mechanisms may help to explain how mitochondrial
      defects contribute to the pathogenesis of neuronal death or dysfunction in
      ischemia/reperfusion injury as well as in human degenerative diseases including
      Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and
      Huntington's disease. This has opened up new avenues for understanding the
      pathogenesis of neurodegeneration and may lead to new and more effective
      therapeutic approaches to these diseases.

PMID- 11223576
TI  - [Virulence factor of Escherichia coli strains isolated during asymptomatic
      bacteriura among patients treated by drugs with acetylcholine antagonistic
      activity in a psychiatric institute].
AB  - In two successive investigations on nosocomial infections in our hospital, wa
      have found that asymptomatic bacteriuria is closely related to age (over 50
      years) and to treatment with acetylcholine antagonistic activity. We therefore
      searched for the presence and expression of genes coding for the virulence
      factors usually present in uropathogenic E. coli in our strains, in strains
      isolated during asymptomatic bacteriura related to neurologic bladder, and in
      strains isolated during symptomatic bacteriura. We found that strains from
      neurologic bladders rarely carried one or two virulence factors while 50% of our
      strains isolated from asymptomatic bacteriuria carriea at least 3 virulence
      factors commonly found in strains isolated from symptomatic urinary tract
      infection. Consequently, it appears important to look for urinary tract infection
      in patients (over 50 years of age) treated with such drugs, and to look for
      virulence factors in case of asymptomatic bacteriura. If the stains carry no
      virulence factors, no antibiotic treatment shoud be instituted but the patients
      should be invited to drink more water than usual in order to promote elimination
      of the strains in the urine. Inversely, if the strains carry virulence factors,
      an adpted antibiotic treatment should be started.

PMID- 11223577
TI  - The influence of mechlorethamine on the activity of ecto-ATPase of rat
      lymphocytes.
AB  - Mechlorethamine, is an immunomodulator widely used in therapy although its effect
      on plasma membrane - bound enzymes is unclear. In rats with an inflammatory
      state, an increased activity of ecto-ATPase was observed both in the B and T
      subpopulations of lymphocytes. A single administration of mechlorethamine
      (simultaneously with carrageenin - inflammation factor), either in
      immunomodulating (5microgram/kg) or cytotoxic (600microgram/kg) dose, decrease
      the enzymatic activity in both subpopulations but to higher degree in the case of
      cytotoxic dose. In in vitro studies, after administering mechlorethamine, a
      diminution of inhibiting potential of the inhibitors blocking the nucleophilic
      site of proteins was noticed. This confirms the hypothesis that mechlorethamine
      attacks the catalytic part of the ecto-enzyme containing a nucleophylic group.
      Classical inhibitors of apyrase - Hg(2+), cerythrosin B and suramine - did not
      cause any significant change in the activity of ecto-ATPase, what confirms the
      fact that these enzymes belong to different groups.

PMID- 11223578
TI  - Synthesis of new N-substituted pyrrolidin-2-ones as cyclic analog of gamma
      aminobutyric acid.
AB  - Some new N-substituted pyrrolidin-2-ones, cyclic analogs of baclofen and of 3-(5
      methylbenzo[b]furan-2-yl)-gamma-aminobutyric acid, have been prepared starting
      from corresponding pyrrolidinones and characterized.

PMID- 11223579
TI  - [Goat's milk in nutrition].
AB  - Compared with cow's milk and mother's milk, goat's milk has biochemical
      properties theoretically favoring its nutritional value. The theoretical
      beneficial effects of goat's milk have incited experimental studies in the pig
      model and clinical studies (particularly in children). They have also inspired
      research on the bioavailability and digestibility of goat's milk and led to work
      improving goat breeds using feeding, genetic or transgenetic methodologies. We
      can expect to see adapted goat's milk food being proposed for children,
      particularly those intolerant to cow's milk, for patients with gastrointestinal
      disease, or even as a supplement for the elderly and malnourished. One can hope
      that the people living in developing countries, where the goat population is the
      most important, will benefit from the production of quality goat's milk.

PMID- 11223580
TI  - [The European directorate for the quality of medicines].
AB  - The tasks of the European Directorate for the Quality of Medicines covers

PMID- 11223581
TI  - [Percutaneous drainage of acute necrotizing pancreatitis: when and how?].

PMID- 11223582
TI  - [Surgical treatment of sterile and infected pancreatic and peri-pancreatic
      necrosis].

PMID- 11223583
TI  - [Treatment of sterile and infected necrosis: the role of interventional
      radiology].

PMID- 11223584
TI  - [Diagnosis of biliary origin of acute pancreatitis].

PMID- 11223585
TI  - [The place of ERCP and sphincterotomy in biliary acute pancreatitis].

PMID- 11223586
TI  - [How should biliary lithiasis be managed?].

PMID- 11223587
TI  - [Can post-ERCP acute pancreatitis be predicted and prevented?].

PMID- 11223588
TI  - [Positive and etiological diagnosis of acute pancreatitis].

PMID- 11223589
TI  - [How is the severity of acute pancreatitis established?].

PMID- 11223590
TI  - [What are the criteria for imputation of drug-induced pancreatitis?].

PMID- 11223591
TI  - [How should th non-complicated forms of acute pancreatitis be managed?].

PMID- 11223592
TI  - [Management of complicated pancreatitis: general complications].

PMID- 11223594
TI  - [Drug-induced pancreatitis. First updated edition of the bibliographic database
      of acute pancreatitis and related drugs].

PMID- 11223593
TI  - [Management of complicated acute pancreatitis: local complications].

PMID- 11223595
TI  - [Management of acute biliary pancreatitis].

PMID- 11223596
TI  - [Can post-ERCP acute pancreatitis be predicted and prevented?].

PMID- 11223597
TI  - [What investigations are indicated for probable non-A-non-B acute pancreatitis?].

PMID- 11223599
TI  - [Bioclinical scores].

PMID- 11223598
TI  - [SIRS during acute pancreatitis: an interesting pathophysiologic concept but with
      poor clinical relevance].

PMID- 11223600
TI  - [Morphological criteria for severity assessment].

PMID- 11223601
TI  - [Practical use of severity indices].

PMID- 11223602
TI  - [Acute pancreatitis: a time for consensus].

PMID- 11223603
TI  - [Management of uncomplicated acute pancreatitis].

PMID- 11223604
TI  - [Are specific treatments efficient?].

PMID- 11223605
TI  - [Treatment of respiratory failure].

PMID- 11223606
TI  - [What is the gold standard for diagnosis?].

PMID- 11223607
TI  - [Treatment of non-respiratory organ failures].

PMID- 11223608
TI  - [Management of nutritional support].

PMID- 11223609
TI  - [Long-term sequelae and quality of life].

PMID- 11223610
TI  - [Definition and evolution].

PMID- 11223611
TI  - [Should patients with acute pancreatitis be given antibiotic prophylaxis?].

PMID- 11223612
TI  - [Contribution of 3D CISS MRI for pre- and post-therapeutic monitoring of
      obstructive hydrocephalus].
AB  - This report describes the use of the recent three-dimensional Fourier transform
      constructing imaging in the steady state (CISS) MR sequence in the management of
      obstructive hydrocephalus. It is a gradient-echo imaging technique with high
      resolution which remains sensitive to flow. It enables locating the obstruction
      and determining the upstream impact. It provides anatomical information about
      third ventricle (V3) morphology and relationships useful before ventriculostomy.
      Twenty patients with obstructive hydrocephalus at the level of cerebral aqueduct
      or posterior V3 underwent sagittal 3DFT-CISS acquisition, supplemented by
      frontal, axial and coronal reformations in the cerebral aqueduct axis. 9 patients
      were examined after ventriculostomy with the same protocol. CISS-3DFT allows good
      visualization of the cerebral aqueduct and diagnosis of the underlying cause of
      obstruction (malformation, tumor), sometimes better than classical sequences. In
      case of complete obstruction, the flow-related signal void is usually absent in
      the cerebral aqueduct or V3. The position of V3 floor and its relationship with
      the tip of basilar artery are well analyzed. The dilatation of the anterior V3
      recesses is a better sign of activity of hydrocephalus - and then of
      therapeutical indication - than classical transependymal resorption signs which
      are not always present in chronic longstanding adult hydrocephalus. Of the 9
      ventriculostomy patients seven had linear flow-related signal void through V3
      floor, from anterior V3 to basal cisterns on the postoperative MR study. This
      flow void confirms patent ventriculostomy.

PMID- 11223613
TI  - [Clinical application of functional MRI: a strategic tool for neurosurgery].
AB  - The purpose was to incorporate preoperative functional imaging data into anatomic
      data of operative microscope for neurosurgical procedures of patients suffering
      from lesions contiguous to eloquent brain areas. The day before surgery, patients
      bearing scalp markers underwent fMRI, just before anatomical contrast-enhanced MR
      images. FMRI data analysis were realised using a t test (p<0.0001). The resulting
      functional-anatomical images were downloaded onto a surgical neuronavigation
      computer in order to outline tumoral target and functional areas. At surgery,
      cortical stimulation has been used to confirm functional data. Functional image
      guided surgery of lesions abutting functional cortex can be safely performed.

PMID- 11223614
TI  - Functional MR imaging and traumatic paraplegia: preliminary report.
AB  - PURPOSE: To evaluate residual activity in the sensorimotor cortex of the lower
      limbs in paraplegia. METHODS: 5 patients suffering from a complete paralysis
      after traumatic medullar lesion (ASIA=A). Clinical evaluation of motility and
      sensitivity. 1. Control functional MR study of the sensorimotor cortex during
      simultaneous movements of hands, imaginary motor task and passive hands
      stimulation. 2. Concerning the lower limbs, 3 fMRI conditions: 1-patient attempts
      to move his toes with flexion-extension, 2-mental imagery task of the same
      movement, 3-peripheral passive proprio-somesthesic stimulation (squeezing) of the
      big toes. RESULTS: Activations were observed in the primary sensorimotor cortex
      (M1), premotor regions and in the supplementary motor area (SMA) during movement
      and mental imaginary tasks in the control study and during attempt to move and
      mental imaginary tasks in the study concerning the lower limbs. Passive
      somesthesic stimulation generated activation posterior to the central sulcus for
      2 patients. CONCLUSION: Activations in the sensorimotor cortex of the lower limbs
      can be generated either by attempting to move or mental evocation. In spite of a
      clinical evaluation of complete paraplegia, fMRI can show a persistence of
      sensitive anatomic conduction, confirmed by Somesthesic Evoked Potentials.

PMID- 11223615
TI  - [Endovascular carotid occlusion: a retrospective study of complications in 33
      cases].
AB  - MATERIAL-METHODS: Thirty three patients (16 men, 17 women), mean age 45 years
      underwent an intravascular carotid balloon occlusion for intracavernous
      aneurysms, carotid-cavernous fistulas or cervical carotid injuries by Fogarty
      balloons (5 patients before 1982) or detachable balloons (28 patients). Transient
      balloon test occlusion consisted in a clinical examination, an angiographic study
      for 32 patients with an electroencephalogram for 16 patients. RESULTS: Early
      complications occurred for four patients by veineous rupture (1 patient) or
      ischemic injury (3 patients). Late complications occurred for two patients by
      ischemic injuries, one asymptomatic. DISCUSSION: These results are similar to the
      literature's results and the transient test occlusion consisting in clinical
      examination, angiographic study and EEG seems to be reliable compared to cerebral
      blood flow determination. CONCLUSION: Even if its indications have decreased
      because of technic improvements permitting carotid flow preservation, carotid
      endovascular balloon occlusion stays a reliable, cheap technic in carotid
      injuries' treatment.

PMID- 11223616
TI  - [Centrosomatic spinal tuberculosis: radiographic features in 10 cases].
AB  - We report a series of 10 cases of centrosomatic tuberculosis of the spine. The
      mean age of the patients was 36 years. Plain x-rays of the spine showed isolated
      defects in 3 cases, a defect with wedge fracture in 3 and a wedge fracture alone
      in 2. A sequestrum was found in 2 cases and bony condensation around the defect
      in 6. A CT scan performed in 3 cases showed, in addition to the bone lesions, a
      perilesional bony condensation in all cases. Soft tissue abscess formation was
      noted in 1 case and epidural involvement in the 2 others. MRI performed in 2
      cases evidenced an alteration of the vertebral body signal with localized
      anterior epiduritis at the site of a small epidural abscess. CT scan and MRI
      contribute usefully to the radiographic diagnosis of centrosomatic tuberculosis,
      evidencing sequestra, bony condensation at the periphery of defects, and the
      presence of soft tissue abscesses and or epidural involvement. When these signs
      are absent, the differential diagnosis may be difficult with other causes of
      tumor formation, requiring vertebral biopsy.

PMID- 11223617
TI  - Locoregional late effects of paravascular thorotrast deposits: results of the
      german thorotrast study.
AB  - PURPOSE: The aim of this study was to assess late effects of long-term exposure
      to alpha irradiation caused by paravascular Thorotrast deposits. SUBJECTS AND
      METHODS: 899 patients, who had received the radioactive contrast medium
      Thorotrast for angiography in the 1930s and 1940s, and 662 controls were followed
      up since 1968 every two years by standardized clinical and laboratory
      examinations. Initially, X-ray plain films of the thorax, upper abdomen and the
      former injection site were performed. In selected patients the sites of
      paravascular Thorotrast deposits were evaluated by ultrasonography, CT and MRI.
      RESULTS: Paravascular Thorotrast deposits were detected in 245 patients. Clinical
      symptoms related to deposits appeared 10 to 30 years after Thorotrast
      administration. The severity of symptoms depended on the location and extension
      of granulomas and were mainly caused by fibrosis, nerve paralysis and vascular
      changes. Four malignant tumors adjacent to granulomas were observed (one soft
      tissue sarcoma in the groin, two squamous cell carcinomas of the parotid gland
      and one lymphoepithelial carcinoma of the nasopharynx). MRI including MRA allowed
      an accurate determination of tissue damage, whereas the utility of US and CT was
      restricted due to strong sound attenuation and streak artefacts caused by the
      high X-ray absorption of Thorotrast. DISCUSSION AND CONCLUSION: Locoregional late
      effects of paravascular Thorotrast deposits mainly comprise radiation induced,
      fibrotic tissue destruction. The incidence of malignant tumors, in particular
      sarcomas, adjacent to deposits, however, is much lower than initially expected.

PMID- 11223618
TI  - [Radioclinical aspects of cerebral and muscular cysticercosis: 20 cases].
AB  - We report a series of 20 cases of cysticercosis. Cysticercosis is a rather wide
      spread disease in North Vietnam with clinical signs such as myalgia, headache,
      epileptic seizures. It is often seen in male adults 30 to 60 years old, not in
      children. CT-scan is a good method for detecting cerebral cysticercosis at
      different stages of evolution: cysts with scolex, calcified cysts or both
      simultaneously, which is the evidence of several successive infestations.
      Muscular cysticerci can be detected by palpation or by radiography when they are
      calcified. Cerebral and muscular locations of cysticercosis are nearly always
      simultaneous, therefore we must always explore these both seats by CT scan (for
      the brain) and by radiography (for the muscles and the subcutaneous tissue).

PMID- 11223619
TI  - [Computed tomographic and/or magnetic resonance imaging exploration of
      degenerative lumbar spine].

PMID- 11223620
TI  - [Solitary plasmocytoma of the calvarium].
AB  - We report a case of 54 year old patient harboring a solitary painless mass of the
      calvarium. There was a well-defined biparietal lytic lesion on plain skull
      radiographics. Computed tomography showed a large hyperdense lesion. This lesion
      was extraaxial and nearly isointense with gray matter on T1 and T2-weighted MR
      images, and diffusely enhanced after gadolinium injection. Angiography showed
      hyperovascularity supplied by middle meningeal and superficial temporal arteries.
      Imaging study bore some similarities to meningioma. A large extra-axial mass with
      an important lytic lesion should have led to the diagnosis of plasmocytoma.

PMID- 11223621
TI  - [Dural metastasis of prostatic adenocarcinoma presenting as acute intracranial
      subdural hematoma: a case report].
AB  - Intracranial malignant metastatic dissemination usually is seen as a unique
      nodular formation enhanced after intravenous injection of contrast medium. Forms
      mimicking meningioma or subdural hematoma have been described. We report a case
      of dural metastasis from an adenocarcinoma of the prostate in a 60-year-old man.
      The CT image suggested acute subdural hematoma.

PMID- 11223622
TI  - [Isolated dorsal extradural hydatid cyst. A case report].
AB  - We report a rare case of spinal cord compression caused by a primary extradural
      hydatid cyst revealed at MRI.

PMID- 11223623
TI  - [A protocol for imaging pediatric brain tumors].
AB  - Children with malignant brain tumors undergo multicentric clinical trials to
      improve standards of care. The considerable variations in imaging practice can
      serve as confounding variables in these studies. The purpose of this report is to
      propose a set of standard diagnostic imaging guidelines to improve the value of
      imaging when used to test the efficacy of treatments in pediatric neuro-oncology.

PMID- 11223624
TI  - [Magnetic resonance imaging of the breast].
AB  - This article reviews the current benefits and limitations of MR imaging of the
      breast. Techniques and results based on a review of the literature are first
      presented then analyzed. This imaging modality is clearly indicated for the
      diagnosis of recurrent disease and clinically occult breast cancers. Its value in
      other fields (neoadjuvant chemotherapy, staging of cancers, genetic cancers) is
      still experimental. Owing to its variable specificity, MRI is not currently
      recommended for the diagnosis of microcalcifications or evaluation of
      asymptomatic mammographically dense breasts. MR-guided interventional procedures
      should improve the value of this technique in breast pathology.

PMID- 11223625
TI  - [Radiologic study of renal colic].
AB  - Ureterolithiasis is a common disease responsible for a large number of admissions
      in emergency departments and a wide utilization of imaging studies. The purpose
      of this review was to analyze the respective role of the different available
      imaging techniques. Intravenous urography is the gold-standard for diagnosis of
      acute obstruction, but positive detection of a stone may prove difficult at
      times. US is less accurate than urography for both diagnoses of obstruction and
      lithiasis, but it represents a non invasive alternative to IVU (no ionizing
      radiation and no IV contrast). The information obtained from measurements of
      intra-renal resistive index is poorly contributive. Non contrast helical CT has
      become the gold-standard for the diagnosis of ureterolithiasis, the two main
      factors limiting its widespread use are its accessibility and the radiation
      exposure. Nevertheless, its excellent diagnostic performance tends to
      dramatically reduce the need for IVU.

PMID- 11223626
TI  - [Malignant stromal tumors of the small intestine: report of 9 cases].
AB  - PURPOSE: Analysis of imaging features of malignant stromal tumors of the small
      bowel and review of literature. MATERIAL AND METHODS: 9 cases of malignant
      stromal tumor of the small bowel with histological proof were imaged at US (8
      cases), small bowel series (9 cases) and CT scan (3 cases). RESULTS: There were 6
      cases of leiomyosarcoma and 3 cases of malignant schwannoma. Tumors involved the
      jejunum in 3 patients, the ileum in 4 patients, and the duodenum in 2 patients.
      The main clinical presentation was an abdominal mass (8 cases), which appeared
      heterogeneous and hypoechoic with eccentric lumen at US confirming its GI origin
      (7 cases). Small bowel series showed a bulky cavitary mass opacified via a thin
      fistula (7 cases), an ileo-ileal intussusception (1 case) and enlarged duodenal
      lumen (1 case). CT performed in 3 cases showed an intraperitoneal mass with soft
      tissue density. A communication with the GI tract was noted in 1 case, and in
      another case, it showed an intestinal intussusception. US guided biopsy performed
      in 3 cases provided diagnosis in 2 cases (malignant schwannoma, leiomyosarcoma).
      Tumor growth was exophytic in 8 cases and dumbbell-shaped in 1 case. CONCLUSION:
      The imaging features of malignant stromal tumors of the small bowel are similar.
      It varies with the type of tumor growth and its size. The diagnosis may be
      suggested based on imaging features.

PMID- 11223627
TI  - [Ultrasound guided alcohol ablation of the celiac plexus in oncology patients
      with abdominal pain].
AB  - PURPOSE: The authors report results of a retrospective study evaluating the
      efficacy of US-guided alcohol ablation of the celiac plexus in 26 patients with
      chronic cancer-related abdominal pain. They review the interest of this imaging
      technique for guidance. PATIENTS AND METHODS: Thirty US-guided alcohol ablations
      were performed in 26 patients. Twenty-two of them had a prancreatic malignancy, 3
      had a gastric cancer and 1 had an esophageal cancer. RESULTS: 72% of patients
      experienced significant pain relief with at least 50% decrease in morphine
      requirements for two months. Four patients underwent a second ablation because of
      persistent pain and 3 of them experienced relief. CONCLUSION: Celiac plexus
      ablation is considered to be one of the most effective treatments for chronic
      cancer-related abdominal pain, often used as an adjuvant treatment in the pain
      management strategy. US guidance is advantageous because it is simple and
      accurate and enables quick needle placement.

PMID- 11223628
TI  - [Absorbed dose during helical acquisition CT. Effect of acquisition parameters].
AB  - PURPOSE: European directive 97/43 specifies that the dose delivered to the
      patient during a radiological procedure should be estimated. In order to prepare
      for implementation of this new regulation, we have studied the dose delivered
      during spiral CT acquisition. MATERIALS AND METHODS: We have studied the
      influence of slice thickness, pitch, tube voltage and intensity, and acquisition
      volume length. We present measurements for single and dual detector CT scanners.
      We used a pencil ionization chamber to measure air kerma. We measured absorbed
      dose in water with a waterproof ionization chamber set in a semi-customized
      phantom filled with water. Chambers were set on the rotation axis of the CT
      scanners. We studied the dose outside the acquisition volume. RESULTS: We
      quantified the influence of each parameter on the absorbed dose. We used our
      measurements to calculate the dose for different acquisition protocols. Also we
      evaluated the dose to organs distant from the acquisition area. CONCLUSION: This
      study is one step toward a systematic estimation of the dose delivered to patient
      during helical CT exams. To use these results in daily practice, we have to
      develop software using our measurements.

PMID- 11223629
TI  - [Value of CT bursography in the evaluation of rotator cuff tears].
AB  - PURPOSE: To describe the technique and assess the value of subacromial CT
      bursography in patients with partial surface tear of the rotator cuff tendon.
      MATERIALS AND METHODS: 15 patients with shoulder pain suggestive of tendinopathy
      or tear of the rotator cuff were evaluated with subacromial CT bursography.
      RESULTS: Subacromial CT bursography was normal in 4 patients. Partial surface
      tear was detected in 7 patients [irregularities (n=2), defect (n=2), superficial
      tear (n=3)]. Full thickness tear was detected in 4 patients. CONCLUSION: The
      authors described the technique for subacromial CT bursography to visualize
      partial surface tears of the rotator cuff tendon. This simple and reliable
      technique could be an alternative to MR imaging, especially when MR evaluation is
      not possible.

PMID- 11223630
TI  - [Intra-arterial fibrinolytic therapy for acute mesenteric ischemia].
AB  - We report a case of mesenteric ischemia secondary to embolic occlusion treated by
      percutaneous intra-arterial thrombolysis. Early initial radiographic evaluation
      included abdominal plain film, ultrasonography, abdominal CT, and arteriography.
      Only selective superior mesenteric artery angiography provided definite
      diagnosis. The duration of ischemic symptoms before thrombolysis was 6 hours.
      Post procedure angiogram at 12 hours showed complete resolution of the mesenteric
      arterial thrombus with clinical improvement. The most important criteria for
      patient survival is early diagnosis and immediate treatment. Direct infusion of
      urokinase into the superior mesentric artery may be an alternative to surgery in
      selected patients and particularly in patients without evidence of frank bowel
      necrosis.

PMID- 11223631
TI  - [Imaging of cloverleaf skull].
AB  - The cloverleaf skull is a rare and due to complex craniosynostosis. This
      malformation can be isolated or associated with extracranial skeletal anomalies.
      This anomaly has a poor prognosis both in terms of neurological outcome and
      esthetic appearance. Our report underscores the need to obtain a global study of
      the skull, the brain and the cerebral vessels with 3D reconstructions and MRI
      prior to early surgery.

PMID- 11223632
TI  - [Septic arthritis of a lumbar facet joint associated with epidural and
      paravertebral soft tissue abscess].
AB  - Septic arthritis of the lumbar facet joint is rare, probably underdiagnosed,
      often associated with complications such as epidural abscess and paraspinal
      muscles abscess. Diagnosis is based on imaging evaluation. Plain radiographs of
      the lumbar spine are not helpful because often nomal. Bone scintigraphy is very
      sensitive but non-specific. CT scan can confirm the diagnosis and guide the
      needle biopsy. MRI is the preferred imaging modality for diagnosis. MRI shows
      early bone and joint involvement and it is helpful in detecting epidural and
      paravertebral soft tissue lesions.

PMID- 11223633
TI  - [Abdominal actinomycosis. Report of 4 clinical cases studied with radiography].
AB  - We report 4 cases of pathologically proven abdominal actinomycosis. US and CT
      demonstrated an infiltrative abdominal mass with ill-defined margins and
      heterogeneous enhancement after IV contrast. The ileo-cecal region was involved
      in one case; the mass appeared following cholecystectomy and recurred 3 years
      after surgical resection in one case; and no predisposing factor was identified
      in the 2 other cases. In one of these, recurrence was observed 12 years after the
      first episode. Actinomycosis must be included in the differential diagnosis of
      invasive abdominal lesions with "malignant" appearance.

PMID- 11223634
TI  - [Quid? Pneumothorax complicating Wegener disease with rupture of pleura of
      cavitary nodule].

PMID- 11223635
TI  - [Stellate ganglion radiofrequency neurolysis. Report of a case followed over a 3
      year period].
AB  - We present the case of a patient who experienced residual ischemic symptoms and
      invalidating chronic pain after an injury where three fingers of his left hand
      were sliced off by a chain saw. He underwent 5 stellate ganglion RF neurolysis
      over a two year period, followed by progressive and complete pain relief. We will
      underscore the value of CT guidance during needle placement and the efficacy of
      RF neurolysis.

PMID- 11223636
TI  - [Clopidogrel? Known or known?].

PMID- 11223637
TI  - Introduction. Oxidative stress in mitochondria disorders of aging.
AB  - These special issues of Biological Signals and Receptors are intended to describe
      mitochondrial DNA damage, oxidative stress and human diseases, including
      neurodegenerative and neuromuscular diseases, disorders associated with aging,
      and ischemia-perfusion injury. Traditionally, mitochondria have been viewed as
      the 'powerhouse' of the cell, i.e., the site of the oxidative phosphorylation
      machinery involved in adenosine triphosphate (ATP) production. Consequently, much
      of the research conducted on mitochondria over the past 4 decades has focused on
      elucidating both those molecular events involved in ATP synthesis by oxidative
      phosphorylation and those involved in the biogenesis of the oxidative
      phosphorylation machinery. While monumental achievements have been made, and
      continue to be made, in the study of these remarkable but extremely complex
      processes essential for the life of most animal cells, it has been only in recent
      years that a large body of biological and biomedical scientists have come to
      recognize that mitochondria participate in other important processes. Two of
      these are cell death and aging which, not surprisingly, are related processes
      both involving, in part, the oxidative phosphorylation machinery. This new
      awareness has sparked a new and growing area of mitochondrial research that has
      become of great interest to a wide variety of scientists ranging from those
      involved in elucidating the role of mitochondria in cell death and aging to those
      interested in either suppressing or facilitating these processes as it relates to
      identifying new therapies or drugs for human disease.

PMID- 11223638
TI  - Protein translocation into mitochondria.
AB  - The biogenesis of mitochondria requires the translocation of most mitochondrial
      proteins across two biological membranes. Mitochondrial preproteins are
      synthesized in the cytosol carrying targeting information, that is recognized by
      specific receptor proteins. The precursor polypeptides are transported across
      both mitochondrial membranes via three large integral membrane protein complexes
      forming specialized preprotein translocases. A soluble protein complex in the
      matrix provides the ATP-dependent translocation force, responsible for the
      movement and unfolding of the bulk polypeptide chain. After the removal of the
      targeting sequence, imported proteins fold into their native conformation with
      the help of chaperone proteins in the mitochondrial matrix.

PMID- 11223639
TI  - Structural changes of mitochondria related to apoptosis.
AB  - The original concept of apoptosis stressed the morphological changes of the
      nucleus, condensation with the aggregation of chromatin, and the intactness of
      intracellular organelles including mitochondria. However, the application of
      molecular biology and flow-cytometric techniques to the research field of
      apoptosis has led to the proposal of the apoptotic processes which emphasizes the
      'swelling of mitochondria' due to the opening of the 'permeability transition
      pores' of the mitochondrial membranes followed by a series of events including
      the collapse of the transmembrane potential of mitochondria and release of
      cytochrome c from mitochondria into the cytosol. Enlargement of mitochondria
      induced by various pathological conditions are classified into two categories:
      the swelling and the formation of megamitochondria (MG). Recently, we have found
      that free radical-induced formation of MG is succeeded by apoptotic changes of
      the cell. If the MG formation is actually related to apoptosis, this will be a
      new aspect of the structural changes of mitochondria involved in apoptosis
      besides the simple swelling of mitochondria. First, we will discuss the 'swelling
      of mitochondria' which characterizes the currently accepted hypothesis on the
      apoptotic processes of the cell, as described above, in the light of the
      literature. Second, the mechanisms controlling the size and distribution of
      mitochondria in the cell are dealt with paying special attention to the genetic
      regulation and cytoskeletons. Third, we have tried to characterize the MG
      formation to correlate apoptotic changes of the cell. Finally, we will discuss
      several problems to be solved in the future which involve mitochondria in
      apoptotic processes of the cell.

PMID- 11223640
TI  - Mitochondrial nitric oxide synthase, oxidative stress and apoptosis.
AB  - Nitric oxide (NO) exerts a wide range of its biological properties via its
      interaction with mitochondria. By competing with O(2), physiologically relevant
      concentrations of NO reversibly inhibit cytochrome oxidase and decrease O(2)
      consumption, in a manner resembling a pharmacological competitive antagonism. The
      inhibition regulates many cellular functions, by e.g., regulating the synthesis
      of ATP and the formation of mitochondrial transmembrane potential (Delta Psi). NO
      regulates the oxygen consumption of both the NO-producing and the neighboring
      cells; thus, it can serve as autoregulator and paracrine modulator of the
      respiration. On the other hand, NO reacts avidly with superoxide anion (O(2)(-))
      to produce the powerful oxidizing agent, peroxynitrite (ONOO(-)) which affects
      mitochondrial functions mostly in an irreversible manner. How mitochondria and
      cells harmonize the reversible effects of NO versus the irreversible effects of
      ONOO(-) will be discussed in this review article. The exciting recent finding of
      mitochondrial NO synthase will also be discussed.

PMID- 11223641
TI  - Peroxynitrite-mediated mitochondrial dysfunction.
AB  - Peroxynitrite anion (ONOO(-)) is a potent biological oxidant produced by the near
      diffusion-limited reaction of superoxide and nitric oxide. Peroxynitrite has been
      implicated in diverse forms of free radical-induced tissue injury. Experimental
      evidence showed that exogenous and endogenous peroxynitrite causes alterations of
      the structure and function of mitochondrial proteins, leading to mitochondrial
      dysfunction and cellular or organ injury. These data are discussed along with its
      physiopathological implications.

PMID- 11223642
TI  - Involvement of mitochondrial phospholipid hydroperoxide glutathione peroxidase as
      an antiapoptotic factor.
AB  - Although reactive oxygen species (ROS) such as superoxide and hydroperoxide are
      known to induce apoptotic cell death, little is known as to the apoptotic death
      signaling of mitochondrial ROS. Recent evidence has suggested that antioxidant
      enzymes in mitochondria may be responsible for the regulation of cytochrome c
      release and apoptotic cell death. This paper examines the current state of
      knowledge regarding the role of mitochondrial antioxidant enzymes, especially
      phospholipid hydroperoxide glutathione peroxidase. A model for the release of
      cytochrome c by lipid hydroperoxide has also been proposed.

PMID- 11223644
TI  - Vitamin E regulation of mitochondrial superoxide generation.
AB  - The mitochondrion is the greatest source, as well as the target, of reactive
      oxygen species (ROS). Increasing evidence indicates that vitamin E can act as a
      biological modifier independently of its antioxidant activity. Experimental
      evidence available shows that vitamin E is capable of dose-dependently regulating
      mitochondrial generation of superoxide and hydrogen peroxide. Vitamin E may
      modulate mitochondrial production and levels of superoxide by preventing electron
      leakage, by mediating the superoxide generation systems directly and/or by
      scavenging superoxide generated. By downregulating mitochondrial generation of
      superoxide and related ROS, vitamin E not only attenuates oxidative damage but
      also modulates the expression and activation of signal transduction pathways and
      other redox-sensitive biological modifiers.

PMID- 11223643
TI  - Mitochondrial creatine kinase in contact sites: interaction with porin and
      adenine nucleotide translocase, role in permeability transition and sensitivity
      to oxidative damage.
AB  - The creatine/phosphocreatine circuit provides an efficient energy buffering and
      transport system in a variety of cells with high and fluctuating energy
      requirements. It connects sites of energy production (mitochondria, glycolysis)
      with sites of energy consumption (various cellular ATPases). The cellular
      creatine/phosphocreatine pool is linked to the ATP/ADP pool by the action of
      different isoforms of creatine kinase located at distinct subcellular
      compartments. Octameric mitochondrial creatine kinase (MtCK), together with porin
      and adenine nucleotide translocase, forms a microcompartment at contact sites
      between inner and outer mitochondrial membranes and facilitates the production
      and export into the cytosol of phosphocreatine. MtCK is probably in direct
      protein-protein contact with outer membrane porin, whereas interaction with inner
      membrane adenine nucleotide translocase is rather mediated by acidic phopholipids
      (like cardiolipin) present in significant amounts in the inner membrane. Octamer
      dimer transitions of MtCK as well as different creatine kinase substrates have a
      profound influence on controlling mitochondrial permeability transition (MPT).
      Inactivation by reactive oxygen species of MtCK and destabilization of its
      octameric structure are factors that contribute to impairment of energy
      homeostasis and facilitated opening of the MPT pore, which eventually lead to
      tissue damage during periods of ischemia/reperfusion.

PMID- 11223645
TI  - Mitochondria in exercise-induced oxidative stress.
AB  - In recent years it has been suggested that reactive oxygen species (ROS) are
      involved in the damage to muscle and other tissues induced by acute exercise.
      Despite the small availability of direct evidence for ROS production during
      exercise, there is an abundance of literature providing indirect support that
      oxidative stress occurs during exercise. The electron transport associated with
      the mitochondrial respiratory chain is considered the major process leading to
      ROS production at rest and during exercise. It is widely assumed that during
      exercise the increased electron flow through the mitochondrial electron transport
      chain leads to an increased rate of ROS production. On the other hand, results
      obtained by in vitro experiments indicate that mitochondrial ROS production is
      lower in state 3 (ADP-stimulated) than in state 4 (basal) respiration. It is
      possible, however, that factors, such as temperature, that are modified in vivo
      during intense physical activity induce changes (uncoupling associated with loss
      of cytochrome oxidase activity) leading to increased ROS production. The
      mitochondrial respiratory chain could also be a potential source of ROS in
      tissues, such as liver, kidney and nonworking muscles, that during exercise
      undergo partial ischemia because of reduced blood supply. Sufficient oxygen is
      available to interact with the increasingly reduced respiratory chain and enhance
      the ROS generation. At the cessation of exercise, blood flow to hypoxic tissues
      resumes leading to their reoxygenation. This mimics the ischemia-reperfusion
      phenomenon, which is known to cause excessive production of free radicals. Apart
      from a theoretical rise in ROS, there is little evidence that exercise-induced
      oxidative stress is due to its increased mitochondrial generation. On the other
      hand, if mitochondrial production of ROS supplies a remarkable contribution to
      exercise-induced oxidative stress, mitochondria should be a primary target of
      oxidative damage. Unfortunately, there are controversial reports concerning the
      exercise effects on structural and functional characteristics of mitochondria.
      However, the isolation of mitochondrial fractions by differential centrifugation
      has shown that the amount of damaged mitochondria, recovered in the lightest
      fraction, is remarkably increased by long-lasting exercise.

PMID- 11223646
TI  - Disturbed surface properties in preterm infants with pneumonia.
AB  - Congenital pneumonia in preterm infants is often associated with respiratory
      insufficiency requiring mechanical ventilation. This study was performed to show
      whether pneumonia in these infants is associated with an inhibition or deficiency
      of surfactant. The ratio of lecithin and sphingomyelin (L/S ratio) and minimal
      surface tension were determined in pharyngeal aspirates from 90 term born infants
      (healthy) and in tracheal aspirates from preterm infants with wet lung (n = 13),
      congenital pneumonia (n = 21) and respiratory distress syndrome (RDS) (n = 90).
      The L/S ratio was lower (p < 0.0001) in the RDS group (8.6) when compared with
      healthy (48.6), wet lung (42.9) and pneumonia (28.9). Surface tension was higher
      (p < 0.001) in RDS (37 mN/m) and pneumonia (33.7) when compared with healthy
      (22.9) or wet lung (21.2). For infants with RDS, L/S ratio <16.5 detects
      surfactant deficiency with 96% specificity and 70% sensitivity, surface tension
      >29 mN/m represents surfactant inhibition (specificity 97%, sensitivity 92%).
      Using these cut-off values in infants with pneumonia, 81% had a sufficient amount
      of surfactant but only 21% of infants with pneumonia had appropriate surface
      tension. Our study shows that lung effluent of respiratory insufficient infants
      with pneumonia, who need mechanical ventilation, has disturbed surface properties
      despite a sufficient amount of surfactant. In these infants, surfactant
      substitution could be beneficial.

PMID- 11223647
TI  - Plasma cortisol, cortisone and urinary glucocorticoid metabolites in preterm
      infants.
AB  - OBJECTIVE AND METHODS: In the fetal circulation, there is a low
      cortisol:cortisone (F:E) ratio ( approximately 0.3) suggesting high activity of
      11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2). The circulating F:E
      ratio rises after birth in term infants, but little is known about infants born
      prematurely. Our hypothesis was that the low fetal plasma F:E ratio would persist
      in infants born prematurely, due to persistently high tissue 11betaHSD2 activity.
      To test this hypothesis, a longitudinal observational study of plasma F, E levels
      and urinary F and E metabolites was performed in 22 preterm infants of 24-31
      weeks gestation. RESULTS: Median plasma F was 234-380 nmol l(-1), median 124-177
      nmol l(-1) from 1 to 14 days age. Plasma F fell with increasing postnatal and
      postconceptional age. The F:E ratio was 3 in the first week of life, and
      thereafter was 1-2, falling with postnatal age. Urinary glucocorticoid
      metabolites were low in quantity ( approximately 48-120 microg kg(-1) day(-1)),
      consisted of E metabolites until term, and did not reflect the plasma F:E ratio.
      CONCLUSIONS: The fetal plasma F:E ratio did not persist in these preterm infants,
      due to tenfold higher levels of F. The F:E ratios were similar to those reported
      in term infants. These data suggest that the low F:E ratio in utero is due to low
      fetal production of cortisol, and effective placental inactivation of maternal F
      by 11betaHSD2.

PMID- 11223648
TI  - Labor pain effects on colostral milk beta-endorphin concentrations of lactating
      mothers.
AB  - beta-Endorphin (beta-EP) levels of colostral milk are approximately two-fold
      higher than in plasma of lactating women, in who concentrations peak at term,
      after the first and second stages of labor. We investigated the effect of labor
      pain and vaginal parturition on colostral beta-EP concentrations (beta-endorphin
      (125)I RIA, Incstar Corp., Stillwater, Minn., USA) of at-term nursing mother, in
      comparison to those having undergone elective cesarean section. Our results show
      that colostral milk beta-EP concentrations of mothers who delivered vaginally are
      significantly higher on the 4th postpartum day (6.0 +/- 0.5 vs. 4.3 +/- 0.4
      pmol/l, respectively; p < 0.01) than colostral levels of mothers who underwent
      cesarean section. These data indicate the important influence of the labor
      process on the colostral opioid galactopoiesis. It is suggested that labor and
      parturition pain may increase colostral milk beta-EP concentrations of lactating
      mothers in order to help the newborn overcome the stressful perinatal events of
      natural labor and delivery.

PMID- 11223649
TI  - Lewis and Secretor gene effects on Lewis antigen and postnatal development of
      Lewis blood type.
AB  - Lewis (Le) and Secretor (Se) gene effects on postnatal change in Lewis antigens
      are described based on the quantitative analysis of Lewis antigens in blood.
      Genuine Lewis blood types were determined by Le and Se genotyping in DNA samples
      obtained from umbilical cord blood and infant blood. Lewis(a) (Le(a)) and
      Lewis(b) (Le(b)) antigen levels were measured by a time-resolved
      fluoroimmunoassay. We found that Lewis phenotypes in infants over 9 months of age
      agreed with the genuine types. In cord blood, the dosage effect of the Se gene on
      antigen levels was observed, but the Le gene effect was not observed. Both Se and
      Le gene effects were observed in newborn babies' blood 3-6 days after birth.

PMID- 11223650
TI  - Can anesthesiologic strategies for caesarean section influence newborn jaundice?
      A retrospective and prospective study.
AB  - RATIONALE AND OBJECTIVES: Neonatal jaundice is a frequent problem in neonatology
      and can be influenced by many factors. Our study arose from the clinical
      observation that among all newborns delivered by caesarean section in our center,
      some had a more intense physiological jaundice. We began by reviewing clinical
      anesthesiological case-sheets to ascertain whether this difference was linked to
      the use of different anesthesiologic strategies. We then performed a prospective
      study on healthy preterm and term newborns to verify this hypothesis. STUDY
      DESIGN: We retrospectively considered all healthy term newborns with weight >
      2,400 g delivered by caesarean section from January 1998 to May 1999. In the
      prospective studies we included healthy term and preterm newborns consecutively
      delivered by caesarean section from May 1999 to December 1999. We excluded
      preterm newborns with gestational age < 31 weeks and with weight < 1,400 g.
      RESULTS: Both in retrospective and in prospective studies anesthetic agents
      employed were isoflurane (A), sevoflurane (B), or bupivacaine (C). The
      statistical comparison of the three groups in retrospective study confirmed the
      clinical observation: the total bilirubin levels were significantly higher in the
      isoflurane group than in the sevoflurane group (p = 0.0000) and bupivacaine group
      (p = 0.0002). Analysis of data from the prospective study on term newborns
      confirmed our previous results. In preterm infants total bilirubin is
      statistically higher in group A starting from 96 h postdelivery. CONCLUSIONS: It
      is likely that anesthetic technique can be included among factors with possible
      influence on neonatal jaundice.

PMID- 11223651
TI  - Ibuprofen affects pro- and anti-inflammatory cytokine production by mononuclear
      cells of preterm newborns.
AB  - The in vitro effect of ibuprofen (IB) on the production of the proinflammatory
      cytokines interleukin (IL) 1beta, IL-6, and tumor necrosis factor alpha (TNF
      alpha) and the anti-inflammatory cytokine IL-10 by cord blood mononuclear cells
      from preterm newborns was compared to that of peripheral blood mononuclear cells
      of adults. Mononuclear cells were incubated without or with lipopolysaccharide in
      the absence or presence of various concentrations of IB. The levels of IL-1beta,
      IL-6, TNF-alpha, and IL-10 in the supernatants were tested by ELISA. The
      mononuclear cells from the two groups responded to IB by an increased secretion
      of IL-6 and TNF-alpha and by a reduced production of IL-10. The pattern of
      response to the drug was similar following stimulation with lipopolysaccharide.
      The IL-1beta production was mostly unaffected by IB. It is suggested that in
      preterm newborns the differences observed in the in vitro proinflammatory
      cytokine production in response to IB, as observed in the present study, or to
      indomethacin, as reported previously, may affect various clinical outcomes using
      these two drugs.

PMID- 11223652
TI  - Hyponatremia and sensorineural hearing loss in preterm infants.
AB  - In a case-control study the role of hyponatremia in the hearing loss of preterm
      infants was investigated. One hundred and sixty-four premature infants treated at
      the neonatal intensive care unit were screened with transient evoked otoacoustic
      emission (TEAOE). In 32 infants TEAOE results indicated the need for further
      investigations. Auditory brainstem response was performed and 22 of 32 cases had
      bilateral hearing impairment (HI). The birth weight and gestational age in the HI
      group were 1,425 +/- 528 g and 30.4 +/- 3.7 weeks. The matched control group
      consisted of 25 infants with a mean birth weight and gestational age of 1,410 +/-
      280 g and 31.1 +/- 2.1 weeks. Significant differences were found between the HI
      and control groups: Apgar score (p < 0.05), pH value (p < 0.01) and pO(2) level
      (p < 0.05) were lower; the total dose of aminoglycosides (p < 0.01), furosemide
      usage (p < 0.01), the maximum pCO(2) level (p < 0.01), incubator stay (p < 0.05)
      and hyponatremia (p < 0.01) were higher, and the duration of hyponatremia (p <
      0.05) was longer in the HI group. Multivariate logistic regression revealed that
      aminoglycoside treatment and hyponatremia were the two most significant factors
      in the development of hearing impairment. These results suggest that
      hyponatraemia is an additional risk factor for hearing loss in preterm infants.

PMID- 11223653
TI  - Effects of impulse noise stimulation on electrocorticogram and heart rate.
AB  - It is now recognized that high-level impulse noises penetrate the uterus of
      pregnant sheep, elevate thresholds of fetal auditory-evoked potential and produce
      damage to fetal inner ear hair cells. However, little is known about functional
      effects of airborne impulse noise on the late-term fetus. In the present study,
      the effects of a series of 20 impulses on the behavioral state of 6 fetal sheep
      were tested. Noise impulses produced 169.3 peak sound pressure level (pSPL) in
      air. Peak levels recorded near the fetal head averaged 161.1 dB. Impulses
      delivered to the fetus during periods of NREM sleep resulted in a decrease in
      average fetal heart rate (FHR) from 185 +/- 22 beats/min (bpm) before stimulation
      to 174 +/- 23 bpm 2-5 s after stimulation (p < 0.05). During REM sleep, an FHR
      acceleration occurred (before stimulation: 177 +/- 24 bpm, after stimulation: 189
      +/- 31 bpm; p < 0.05). Impulse exposure during NREM sleep resulted in reductions
      in delta-, theta- and alpha-band powers. As a consequence, total power decreased
      from 100 to 72 +/- 16% (p < 0.05). During REM sleep, stimulation provoked a short
      decrease in total band power from 100 to 73 +/- 20% and a similar decrease in the
      theta- and beta-band powers. The results indicated that impulse noise evoked
      short-term alterations in FHR and cortical activity. These changes were mediated
      by auditory brain stem activation that led to cortical desynchronization during
      both NREM and REM sleep in late-term fetal sheep.

PMID- 11223654
TI  - Brainstem nitric oxide tissue levels correlate with anoxia-induced gasping
      activity in the developing rat.
AB  - Gasping is an important mechanism for survival that appears to be developmentally
      modulated by the glutamate-nitric oxide (NO) pathway. However, the temporal
      characteristics of NO brain tissue levels during gasping are unknown. We
      hypothesized that during anoxia-induced gasping, the gasping frequency would be
      closely correlated with caudal brainstem tissue NO concentrations in developing
      rats. Brainstem and cortical tissue NO levels were measured during anoxia using a
      voltammetric electrode in adult rats and 5-day-old pups during control conditions
      and following pretreatment with the NMDA receptor antagonist MK-801 (1 mg/kg) or
      the neuronal NO synthase inhibitor 7-nitro-indazole (7-NI; 100 mg/kg). In young
      animals, NO tissue levels followed a triphasic trajectory coincident with gasp
      frequency which was markedly altered by MK-801 and 7-NI, albeit with preservation
      of gasp frequency-NO tissue level relationships. In adult rats, 40-fold higher NO
      tissue levels occurred and followed a monophasic trajectory coincident with gasp
      patterning. In the cortex, monophasic increases in NO levels occurred at all
      ages. We conclude that anoxia-induced gasping neurogenesis is modulated via NMDA
      NO mechanisms in the developing rat. We postulate that higher NO brainstem
      concentrations may favor early autoresuscitation, but limit anoxic tolerance.

PMID- 11223655
TI  - Perinatal expression of heat-shock protein 90 in different regions of the brain
      and in non-neural tissues of the piglet.
AB  - Important stressful events occur at birth or within the few hours that follow. To
      establish a possible involvement of stress proteins, expression of heat-shock
      protein 90 was determined by Western blotting in several regions of the brain and
      in non-neural tissues of the developing piglet (fetal to 10 days and adult).
      Expression was found in all the tissues studied. While comparable values were
      found in the whole brain during development, decreased expressions were observed
      from 4 to 8 h to 2 days after birth in cerebellum, cortex, hypothalamus and
      striatum. In hippocampus, low expression was observed from 4 h postnatally
      onward. In non-neural tissues, low expression was observed after birth and in the
      adult for heart, liver and lungs. In kidney, low values were found from birth to
      1 day of age. Changes in environmental parameters like temperature and/or hypoxia
      can be related to differential expressions of heat-shock proteins and they
      possibly result in severe developmental outcomes. The results are discussed in
      terms of using the newborn piglet as a model for the study of different forms of
      stress on the heat-shock protein expression during postnatal development.

PMID- 11223656
TI  - Promoting effect of colostrum on the phagocytic activity of bovine
      polymorphonuclear leukocytes in vitro.
AB  - Bovine colostrum contains a variety of essential nutrients, antibodies,
      cytokines, hormones, and growth factors that are important for nutrient supply,
      host defense, growth and for general neonatal adaptation. We have investigated
      the effect of bovine colostrum on the phagocytic activity for latex particles by
      normal peripheral blood polymorphonuclear leukocytes using flow cytometric
      analysis. The phagocytosis promoting effect was observed in colostrum. The
      promoting activity showed dose-dependent increase up to 25% at a concentration of
      colostrum. This activity was maximum in the colostrum obtained at parturition and
      gradually decreased with the time course of lactation as well as IgG level.
      Colostrum possessed the higher promoting activity than milk and normal serum.
      These results indicate that bovine colostrum strongly activates polymorphonuclear
      leukocyte phagocytosis, suggesting the concernment with development of
      nonspecific immune system in newborns.

PMID- 11223657
TI  - Relevance of experimental ischemia in cats for stroke management: a comparative
      reevaluation.
AB  - Repeat studies in animal models of acute focal ischemia can be compared to
      incidental studies in the course of ischemic stroke in order to shed light on the
      development of changes causing ischemic infarcts or recovery of critically
      perfused tissue. Positron emission tomography (PET) studies of regional cerebral
      blood flow, cerebral metabolic rate for oxygen, oxygen extraction fraction (OEF),
      cerebral metabolic rate of glucose and flumazenil (FMZ) binding in the cat middle
      cerebral artery occlusion (MCAO) model and in patients with acute ischemic
      hemispheric stroke were reviewed. After permanent MCAO, the development of
      "misery-perfused" penumbral tissue and its centrifugal conversion into necrosis
      could be demonstrated, resembling focal pathophysiological changes in patients
      with ischemic attacks. In the experimental model and in vascular insults in
      humans, a chance of recovery existed if collateral perfusion developed
      spontaneously within the first hours. In transient MCAO, reperfusion was only
      effective in preventing infarction when it was initiated as long as misery
      perfusion persisted; in these cases tissue was salvaged and large infarcts did
      not develop. In the other instances when oxygen metabolism broke down, and an
      increased OEF was no longer seen, reperfusion even at levels above preocclusion
      had no effect, and large space-occupying infarcts developed. These experimental
      findings are comparable to the variable outcome after thrombolytic therapy; if
      reperfusion is achieved within the therapeutic window of tissue viability, large
      infarcts are prevented and complete or partial recovery can be achieved. In the
      experimental model of focal ischemia and in human stroke, FMZ can be utilized as
      a marker of neuronal integrity. If FMZ binding in the cortex is decreased below 4
      times the mean value of white matter in the acute stage, permanent infarcts were
      observed on late CT/MRI; this irreversible damage could not be prevented by
      thrombolytic therapy. These results demonstrated that PET studies in suitable
      ischemia models in cats can help to explain various courses and diverging
      outcomes of acute ischemic stroke. Comparable findings from experimental ischemia
      and human stroke may affect the selection of appropriate therapeutic strategies.

PMID- 11223658
TI  - Economic evaluation in stroke research. An introduction.
AB  - BACKGROUND AND PURPOSE: Before developing new medical facilities or adapting
      existing facilities in the field of stroke, it is desirable to assess not only
      the medical, but also the economic consequences of such facilities. Economic
      evaluation studies differ from other outcome studies in the way that costs are
      compared with effects. The purpose of this paper is to give an insight into
      economic evaluation studies in the field of stroke, so that these studies become
      easier for neurologists to understand and to apply. SUMMARY OF THE ARTICLE:
      Crucial aspects in economic evaluation research are addressed successively, such
      as the techniques used and how the results can be influenced by the perspective
      of the study. The article also considers the inclusion of costs and consequences
      in economic evaluation research. At the end of this article, special issues in
      economic evaluation studies are presented such as discounting, sensitivity
      analysis, incremental analyses and ratios. CONCLUSIONS: Although neurologists
      have no direct responsibility for allocating scarce resources in the field of
      stroke, they are confronted with the results of these decisions in their everyday
      work. Because of this, it might be useful to have clear understanding of economic
      evaluation studies and their caveats.

PMID- 11223659
TI  - Type III collagen deficiency in a family with intracranial aneurysms.
AB  - We present a family with 2 female cousins with intracranial aneurysms and type
      III collagen deficiency. DNA analysis revealed no mutations in the COL3A1 gene,
      encoding type III collagen, and including the segment encoding the C-propeptide
      of type III collagen. The 2 patients with low type III collagen production and
      intracranial aneurysms had inherited different type III collagen alleles. The
      type III collagen deficiency in this family may results from defects during
      posttranslational modification or from an altered collagen metabolism.

PMID- 11223660
TI  - Absence of circulating microemboli in patients with atrial fibrillation
      undergoing electric cardioversion.
AB  - Electrical cardioversion (CV) of atrial fibrillation (AF) is associated with an
      increased risk of stroke, and its appropriate prevention is still a matter of
      debate. It is known that, besides dislodgement of pre-existing intra-atrial
      thrombi, the "stunned" atrium after CV is an important cause of thrombus
      formation and subsequent embolism. We investigated whether CV of AF is associated
      with occurrence of circulating microemboli (ME) representing a sensitive marker
      of the actual thromboembolic activity. Twenty-nine patients (22 men) aged 54 +/-
      13 years suffering from valvular (n = 5) or nonvalvular (n = 24) AF were studied.
      All but 1 patient (with recent-onset AF) had been put on oral anticoagulation
      (INR >2.0) for at least 3 weeks before and 4 weeks after successful CV. In all
      patients, exclusion of internal carotid artery stenosis and atrial thrombus was
      performed prior to CV. Five unilateral 1-hour transcranial Doppler ME monitorings
      over the middle cerebral artery were performed (1) before CV, and (2)
      immediately, (3) 4-6 h, (4) 24 h, and (5) 2-4 weeks after CV. Total absence of
      circulating ME was found before CV as well as during a cumulative monitoring time
      of 115 h after successful CV. Electrical CV of AF after at least 3 weeks of
      effective anticoagulation is not associated with occurrence of cerebral
      circulating ME. This finding requires further investigation including high-risk
      patients with AF undergoing CV based on different treatment protocols.

PMID- 11223661
TI  - Twenty-four-hour blood pressure changes in the course of lacunar disease.
AB  - BACKGROUND: Changes in blood pressure (BP) over time have not been considered in
      investigations on the relationship between BP and cerebrovascular disease (CVD).
      OBJECTIVE: To investigate BP changes throughout a 24-hour period in lacunar
      infarct patients with different outcomes. METHODS: Twelve control subjects (group
      1) and 56 patients with symptomatic lacunar infarcts were studied. The infarct
      patients were divided into three groups: group 2, 25 patients with a fair outcome
      without any cerebrovascular attack or progressive dementia (mean follow-up
      period: 4.4 years); group 3, 14 patients with worsening of clinical dementia
      rating and silent lesions, which included lacunae and diffuse white matter
      lesions (4.5 years), and group 4, 17 patients who developed symptomatic infarcts
      (1.7 years). MRIs and ambulatory BP monitoring were performed for each patient on
      two separate occasions. No patient was treated with antihypertensive agents
      during the course of the study. RESULTS: In group 2, the second measurements were
      significantly higher than the first for 24-hour systolic BP (SBP), daytime SBP,
      24-hour diastolic BP (DBP), daytime DBP (p < 0.01, for all) and nighttime DBP (p
      < 0.05). In group 3, the second measurements were significantly lower than the
      first for 24-hour SBP, daytime SBP, 24-hour DBP, and daytime DBP (p < 0.01, for
      all). In group 4, the second measurements were significantly lower than the first
      for 24-hour SBP and daytime SBP (p < 0.01). The correlation between BP and pulse
      rate became positive for group 2 in second measurements, but was not positive for
      groups 3 and 4. CONCLUSIONS: BP tended to elevate over time in patients with a
      fair outcome. In contrast, BP tended to decrease in those who developed dementia
      and symptomatic infarct. Autonomic functions including sympathetic activity might
      play a role in changes in BP in lacunar infarct patients during the course of
      disease.

PMID- 11223663
TI  - Evaluation of the secretory pattern of plasma arginine vasopressin in stroke
      patients.
AB  - Arginine vasopressin (AVP) may play a role in the development of ischemic brain
      edema and/or cerebral vasospasm. Data available on AVP plasma levels in ischemic
      stroke are few and discordant. In order to ascertain whether changes in AVP
      plasma levels occur in ischemic stroke, plasma AVP levels, plasma osmolality and
      mean arterial pressure were determined in 24 patients with unprecedented ischemic
      cerebral infarction and in 15 controls over a 24-hour period. In stroke patients,
      mean 24-hour plasma AVP levels (7.2 +/- 0.8 ng/l) were higher (p < 0.05) than in
      control subjects (2.4 +/- 0.3 ng/l), and correlated with the severity score of
      the neurologic deficit and the mean size of the lesion. In patients with a more
      severe neurologic deficit, the mean 24-hour plasma AVP levels (8.7 +/- 1.0 ng/l)
      were higher than in patients with a less severe neurologic deficit (5.2 +/- 0.8
      ng/l). Data indicate that in ischemic stroke an increased AVP secretion occurs
      independently of osmotic or baroreceptorial mechanisms. The possibility that AVP
      may play a role in neuronal cell damage following cerebral ischemia warrants
      further attention.

PMID- 11223662
TI  - Echo-enhanced transcranial color-coded duplexsonography to study collateral blood
      flow in patients with symptomatic obstructions of the internal carotid artery and
      limited acoustic bone windows.
AB  - We prospectively evaluated 30 consecutive patients with echo-enhanced
      transcranial color-coded duplexsonography (TCCD) and correlative transfemoral
      digital subtraction angiography to assess the diagnostic efficacy of echo
      enhanced TCCD for evaluation of collateral pathways through the circle of Willis
      in patients with limited acoustic bone windows and critical symptomatic carotid
      disease. Echo-enhanced TCCD detected collateral blood flow through the anterior
      communicating artery in 16 of 18 patients (sensitivity 89%, 95% CI 65-99%) and
      was false positive in one out of 12 patients without collateral flow (specificity
      92%, 95% CI 59-100%). For the posterior communicating artery, sensitivity was
      11/14 (79%, 95% CI 49-95%) and specificity was 15/16 (94%, 95% CI 70-100%). Echo
      enhanced TCCD enables to study collateral blood flow through the communicating
      arteries of the circle of Willis with high sensitivity and specificity in
      patients with obstructions of the internal carotid artery and limited acoustic
      bone windows.

PMID- 11223664
TI  - Prediction of the final infarct volume within 6 h of stroke using single photon
      emission computed tomography with technetium-99m hexamethylpropylene amine oxime.
AB  - BACKGROUND: A simple method to predict the final infarct volume within 6 h of
      onset of hemispheric ischemic stroke based on the measurement of cerebral blood
      flow (CBF) using single photon emission computed tomography (SPECT) with
      techneticum-99m hexamethylpropylene amine oxime ((99m)Tc-HMPAO) was investigated
      in a clinical model involving patients without definite early reperfusion or
      clinical recovery. METHODS: A group of 16 patients (group 1) was used to
      establish the methodology, which was then validated in a second group of 14
      patients (group 2). The final infarct volume was defined using computed
      tomography (CT) performed at least 7 days after stroke. The relative CBF
      threshold value, expressed as a percentage of the mean contralateral hemispheric
      value, which most closely estimated the final infarct size on coregistered CT was
      established for each patient. RESULTS: The mean threshold CBF value for group 1
      was 63.7%. When this value was used to predict infarct size in group 2, a close
      correlation was observed between the actual and the estimated sizes (r = 0.973, p
      < 0.0001). This value was not time dependent. CONCLUSIONS: If no significant
      early reperfusion or clinical recovery occurs, a CBF threshold value of 63.7% on
      (99m)Tc-HMPAO SPECT performed within 6 h of stroke onset will reliably predict
      the final infarct size.

PMID- 11223665
TI  - Comparison of MRI perfusion imaging and single photon emission computed
      tomography in chronic stroke.
AB  - There have been few direct comparisons between MR perfusion-weighted imaging
      (PWI) and established perfusion imaging techniques, and none in chronic stroke.
      We therefore studied 17 chronic hemispheric infarction patients (mean, 90 days)
      and compared hypoperfusion volumes determined from PWI maps of relative cerebral
      blood flow (rCBF) and volume (rCBV), and mean transit time (rMTT) with those
      measured with (99)Tc-HMPAO single photon emission computed tomography (SPECT).
      Comparisons were also made between infarct size (T(2)-WI) and clinical scales.
      Correlations were found between lesion location and volume in all three PWI
      hemodynamic parameter maps with clinical state and lesions on SPECT and T(2)-WI.
      In 3 patients, rCBF and rCBV lesions extended well beyond the borders of moderate
      sized infarctions. We conclude that in chronic stroke, PWI can delineate regions
      of abnormal perfusion that reflect the degree of functional impairment and
      structural damage. The finding of peri-infarct hypoperfusion suggests that PWI
      may have the potential to provide a rapid and non-invasive template against which
      interventional strategies aimed at promoting functional recovery may be
      investigated.

PMID- 11223666
TI  - Paranoid (delusional) disorder associated with tuberothalamic artery territory
      infarction.

PMID- 11223667
TI  - Dissecting aneurysm of the vertebral artery with an accessory posterior inferior
      cerebellar artery: successful management with clipping between the two posterior
      inferior cerebellar arteries.

PMID- 11223668
TI  - Inherited thrombophilic conditions, patent foramen ovale and juvenile ischaemic
      Stroke.

PMID- 11223669
TI  - Delayed brain hemorrhage after radiotherapy.

PMID- 11223670
TI  - Current status of cytotoxic chemotherapy in hormone refractory prostate cancer.
AB  - Adenocarcinoma of the prostate is the most prevalent neoplastic disease in men
      and continues to be a major cause of morbidity and mortality. Death from prostate
      cancer is associated with objective and biochemical progression following
      hormonal manipulations often described as hormone refractory prostate cancer
      (HRPCA). Therapy for HRPCA is primarily palliative and therapeutic efficacy has
      to be balanced against potential treatment-related side effects. Therapeutic
      efficacy may be assessed by evaluating the percentage of patients obtaining a PSA
      decline of > 50%, evaluating the response of bidimensionally measurable disease
      or by improvements in quality of life assessments. The most effective cytotoxic
      therapies at the present time seem to be combinations of estramustine phosphate
      with taxanes and etoposide. Regimes employing ketoconazole with estramustine,
      vinblastine or bisphosphonates seem to be worthy of further evaluation.
      Mitoxantrone has an impressive palliative effect in patients, particularly when
      combined with hydrocortisone. Oral chemotherapeutic regimens with a combination
      of estramustine phosphate, cyclophosphamide and prednisone appear to offer a less
      toxic alternative. For the future we need prospective randomized clinical phase
      III studies, prognosticators identifying patients as being at high or low risk
      who might benefit from different therapeutic approaches and generally binding
      eligibility and response guidelines in order to be able to compare trials of
      different therapeutic approaches.

PMID- 11223671
TI  - Early detection of prostate cancer in Germany: a study using digital rectal
      examination and 4.0 ng/ml prostate-specific antigen as cutoff.
AB  - OBJECTIVE: While international screening studies for prostate cancer are by now
      almost reaching the estimated number of recruitments mandatory for the necessary
      power to investigate an effect on mortality of prostate cancer, no statistical
      figures on the detection of prostate cancer in Germany - apart from historical
      data before the use of prostate-specific antigen (PSA) are available. In order to
      generate a database and to investigate the diagnostic efficacy of the primarily
      practice-based urological care system, a case finding study designed as a
      nationwide longitudinal early detection trial was initiated. METHODS: In one week
      in November 1997, 963 urologists prospectively examined 11,644 men between 45 and
      75 years of age by digital rectal examination (DRE) and PSA with 4.0 ng/ml as
      cutoff. Data of family history and physical examination were collected by
      questionnaire. At this time participants were not aware of their PSA value. PSA
      was determined in the study center. Indication for sextant biopsy was a PSA value
      above 4.0 ng/ml or a suspicious lesion on DRE. Any indicated biopsy not performed
      had to be clarified. In a second questionnaire results of prostate biopsy,
      treatment and tumor status were documented. RESULTS: The mean age of the study
      population was 62 years (median 62). The PSA median was 1.4 ng/ml with 82.8%
      presenting with < 4.0 ng/ml, 12.8% with 4-10 ng/ml and 4.4% with >10 ng/ml. From
      1,115 men (47.7%) biopsied, 262 cancers were detected resulting in a detection
      rate of 23.5%. While 399 men refused biopsy, further investigation was not
      recommended in 387 men by their urologist, because prostatitis or benign
      hyperplasia was thought to be the cause for elevated PSA. From the 143 patients
      undergoing radical prostatectomy, 93 (65%) cancers were organ confined. T(1c)
      cancers with elevated PSA > 10 ng/ml could be treated with curative intent in 44%
      only. The positive predictive value (PPV) was estimated to be 16% for DRE alone
      (14/90), 17% for PSA alone (143/819) and 51% for the combination of both
      (105/206). In that cohort, use of age-adjusted PSA values and PSA density
      increased the PPV of PSA testing nonsignificantly. CONCLUSIONS: Significant
      higher PPV indicated that utilizing a combination of both DRE and PSA is most
      effective in the early detection of prostate cancer. Unnecessary biopsies can be
      avoided using either age-adjusted PSA value or PSA density, but the PPV is not
      significantly changed and potentially curable cancer is missed in up to 25%.
      Given the substantial variability of the diagnostic approach despite the study
      design, uniform guidelines are necessary to ensure countrywide sufficient
      screening.

PMID- 11223672
TI  - Expression and prognostic value of CD44 standard and variant v3 and v6 isoforms
      in prostate cancer.
AB  - BACKGROUND: The adhesion molecule CD44 standard (CD44s), and its variant isoforms
      v3 and v6 are associated with cell-to-cell adhesion. The down-regulation of CD44
      standard and its variant isoform CD44v6 is linked with early cancer cell
      dissemination, but the relationship between CD44v3 and malignant features of
      prostate cancer (PC) has not been established previously. METHODS: The expression
      of CD44s and its CD44v3 and CD44v6 isoforms was analysed by immunohistochemistry
      in 209 archival PC biopsy specimens to establish their prognostic value. RESULTS:
      Down-regulation of CD44s and CD44v6 was related to high T classification,
      metastasis, high Gleason score, DNA aneuploidy, high S-phase fraction, high
      mitotic index, perineural growth and dense amount of tumour infiltrating
      lymphocytes (p < 0.03 for all). Down-regulation of CD44s and CD44v6 was related
      to poor survival in the entire cohort (p < 0.0001), in M0 tumours (p < 0.001) and
      in T1-2M0 tumours (p < 0.05). In needle biopsies and TURP specimens, the
      prognostic impact of the investigated parameters was similar. In the multivariate
      analysis, T classification (p = 0.0009), presence of metastases (p < 0.0001),
      Gleason score (p = 0.0060) and CD44v6 (p = 0.0220) expression were independent
      prognostic factors. In M0 tumours, T classification (p < 0.0001) and CD44v6 (p =
      0.003) independently predicted survival. CONCLUSION: Down-regulation of CD44s and
      its CD44v6 isoform is related to tumour malignancy and unfavourable prognosis in
      PC.

PMID- 11223673
TI  - Management of lower urinary tract symptoms of elderly men in Austria.
AB  - OBJECTIVES: The aim of this nation-wide study was to determine the current
      management of elderly men with lower urinary tract symptoms (LUTS) due to benign
      prostatic hyperplasia (BPH) and benign prostatic enlargement (BPE) in Austria,
      and to assess changes over a 4-year study period from 1995 to 1998. METHODS: The
      annual figures of prostatectomies performed in Austria from 1995 to 1998 were
      collected from the Austrian Institute for Health Affairs. Sales figures for
      finasteride, alpha(1)-receptor blockers and plant extracts were obtained from IMS
      market sales and Austrian regional compulsory insurance companies. These data
      were correlated with the number of males living in Austria during the study
      period and to the estimated numbers of elderly men with moderate and severe LUTS
      in this country. RESULTS: The annual number of transurethral resections of the
      prostate (TURPs) decreased from 6,302 in 1995 to 5,297 in 1998 (-16%), and the
      number of open prostatectomies from 506 to 469 (-7%). Extrapolation of these data
      to 100,000 men aged > or = 55 years revealed that 0.76% underwent TURP in 1995,
      this figure decreased to 0.59% in 1998. Market sales of alpha(1)-receptor
      blockers increased by 497% during the study period and those of finasteride by
      1.6%, while plant extract market sales declined by 18.2%. In 1998, plant extracts
      comprised 43.3% of the total BPH market, alpha(1)-receptor blockers 41.5% and
      finasteride 15.2%. CONCLUSIONS: During the years 1995-1998, significant changes
      in medical and surgical BPH therapy were observed in Austria. These data provide
      the basis for a comparison to the situation in other countries and serve as a
      baseline investigation for future studies in this country.

PMID- 11223674
TI  - Hyperinsulinaemia as a risk factor for developing benign prostatic hyperplasia.
AB  - OBJECTIVE: To determine the validity coefficient of the total prostate gland
      volume as an expression of the transition zone (TZ) volume. To test the
      hypothesis of hyperinsulinaemia as a causal factor for the development of benign
      prostatic hyperplasia (BPH). PATIENTS AND METHODS: Three hundred and seven
      consecutive patients with lower urinary tract symptoms were studied. A subgroup
      of 114 patients were tested with regard to the validity coefficient between the
      total prostate gland volume and the TZ volume. In the total material of 307 men,
      a BPH risk factor analysis was performed in which groups of men with the
      following conditions were related to the annual BPH growth rate: men without or
      with metabolic disease; men with different components of the metabolic syndrome,
      and men with low or high fasting plasma insulin values. The prostate gland volume
      and the TZ volume were determined using ultrasound. The presence of non-insulin
      dependent diabetes mellitus (NIDDM) and treated hypertension was obtained from
      the patients' medical records. Data on blood pressure, waist and hip measurement,
      body height and weight were collected and body mass index and waist/hip ratio
      were calculated. Blood samples were drawn from fasting patients to determine the
      insulin and HDL-cholesterol values. RESULTS: In the subgroup of men subjected to
      measurement of both the total prostate gland volume and the TZ volume, the
      correlation coefficient between total prostate gland volume and the TZ volume was
      r.s. = 0.97 (p < 0.0001) which, thus, constituted the validity coefficient. The
      median annual BPH growth rate in the total group was 1.03 ml/year. The median
      annual BPH growth rate was faster in men with metabolic disease (p < 0.0001),
      NIDDM (p < 0.0001), treated hypertension (p < 0.0001), obesity (p < 0.0001) and
      dyslipidaemia (p < 0.0001) than in men without metabolic disease. Moreover, the
      annual BPH growth rate correlated positively with the diastolic blood pressure
      (r.s. = 0.27; p < 0.001), the BMI (r.s. = 0.22; p < 0.001) and four other
      expressions of obesity, and negatively with the HDL-cholesterol level (r.s. = 
      0.15; p < 0.001). The median annual BPH growth rate was faster in men with a high
      than in men with a low fasting plasma insulin level (p = 0.019). When the
      patients were divided into quartiles, the median annual BPH growth rate increased
      statistically significantly with increasing fasting plasma insulin levels. The
      fasting plasma insulin values correlated with the annual BPH growth rates (p =
      0.009). When performing a multivariate analysis using the total prostate gland
      volume as dependent variable, fasting plasma insulin (p = 0.001) and age (p <
      0.001) became statistically significant. CONCLUSION: The results of the present
      report suggest that the total prostate gland volume constitutes a valid
      expression of BPH. The findings support the hypothesis that hyperinsulinaemia is
      causally related to the development of BPH and generate the hypothesis of an
      increased sympathetic nerve activity in men with BPH.

PMID- 11223675
TI  - Relevance of p53 gene alterations for tumor recurrence in patients with
      superficial transitional cell carcinoma of the bladder.
AB  - PURPOSE: The prognostic relevance of p53 protein accumulation in muscle-invasive
      bladder carcinoma is well documented, but the prognostic relevance of p53
      alterations in superficial bladder tumors remains uncertain. Immunohistochemical
      data are divergent, possibly because of the use of nonstandardized techniques. We
      therefore investigated the relevance of p53 gene point mutations and loss of
      heterozygosity (LOH) for tumor recurrence. The results of this molecular analysis
      were compared with accumulation of the p53 protein as shown by
      immunohistochemistry. MATERIAL AND METHODS: Representative tumor tissue was
      selected and microdissected from 40 patients (pTa, 18 patients; pT1, 22 patients;
      grade I, 7 patients; grade II, 28 patients; grade III, 5 patients). Polymerase
      chain reaction (PCR) was carried out with exons 5-8. All PCR products were
      screened for p53 mutations with temperature-gradient gel electrophoresis (TGGE).
      When mobility shift was observed, direct nucleotide sequencing was performed.
      Detection of LOH was performed with nonradioactive microsatellite analysis using
      three markers (TP 53, D17S513 and D17S786) on chromosome 17p.
      Immunohistochemistry was performed with the DO 7 antibody. Tumor samples with p53
      accumulation of 5% or more positive nuclei were classified as positive.
      Univariate analysis for disease-free survival was performed using Kaplan-Meier
      analysis and the log-rank test. RESULTS: TGGE and direct sequencing detected
      mutations in 10 of 40 patients (2 of 18 pTa and 8 of 22 pT1 patients). LOH was
      detected in 11 patients. Both a mutation and LOH were detected in 3 patients. p53
      immunohistochemistry detected at least 5% positive nuclei in 28 of 40 patients
      (70%). After a median follow-up of 26 months 14 patients suffered disease
      recurrence. Whereas disease-free survival did not correlate with a mutation (p =
      0.77, log-rank test), LOH (p = 0.2) or a mutation in combination with LOH (p =
      0.23), a positive p 53 immunoreaction was significantly associated with short
      disease-free survival (p = 0.009). CONCLUSION: Despite the relatively high
      percentage of patients with p53 gene alteration in this population no significant
      correlation between the detection of molecular alteration and disease recurrence
      could be found. We conclude that, in contrast to immunohistochemical
      accumulation, gene alterations play only a minor role in tumor recurrence of p53
      in patients with superficial transitional cell carcinoma of the bladder, and that
      immunohistochemical accumulation of the p53 protein has to be explained by
      mechanisms other than gene mutations.

PMID- 11223676
TI  - Prognostic implications of aberrations in p16/pRb pathway in urothelial bladder
      carcinomas: a multivariate analysis including p53 expression and proliferation
      markers.
AB  - OBJECTIVE: To assess the prognostic value of the expression of two negative
      regulators of the cell cycle, namely CDKN2/INK4a gene product (p16) and
      retinoblastoma gene product (pRb), in urinary bladder cancer in relation to
      clinicopathological parameters, proliferative fraction and p53 protein
      accumulation. METHODS: Paraffin sections from 139 patients with urothelial
      carcinomas were stained immunohistochemically with antibodies to p16 (F12), pRb
      (PMG3-245), p53 (DO1), PCNA (PC10) and Ki-67 (MIB-1). RESULTS: Diminished p16 and
      pRb expression occurred in 29 and 74% of cases, respectively, being associated
      with advanced stage but not with histological grade, papillary status or
      proliferation rate. In most cases (53%) with some fault in the p16/pRb pathway,
      only one gene was affected. A double-negative p16/pRb phenotype was comparatively
      uncommon (25%) and was usually seen in T3-T4 tumours. In survival analysis
      (either univariate or multivariate) aberrant p16 expression was an adverse
      prognostic parameter only in T3-T4 tumours. In contrast, the abnormal p16/pRb and
      p53/p16 phenotypes were linked to a diminished overall and disease-free survival
      (univariate analysis); p53/p16 abnormal expression was also found to be an
      independent predictor of reduced survival in muscle-invasive tumours, while
      proliferation markers were the only parameters with independent significance in
      superficial (Ta-T1) tumours. CONCLUSION: Our results suggest that lack of p16
      immunoexpression, when combined with p53 accumulation, plays an important role in
      determining the clinical outcome in muscle-invasive urothelial carcinomas.

PMID- 11223678
TI  - Penile length and circumference: a study on 3,300 young Italian males.
AB  - OBJECTIVE: The knowledge of normal variations in the size of male external
      genitalia is of considerable interest to several disciplines. We carried out an
      extensive study in young Italian males to provide estimates of normal variations
      of penile dimensions. METHODS: The penile length in flaccid and stretched states
      and the penile circumference were measured in a random group of 3,300 young men
      aged 17-19 years and free from endocrine disorders and from congenital or
      acquired abnormalities of the penis. In a random sample of 325 subjects of the
      same set of people, penile length and circumference were also correlated with
      weight and height. Statistical analysis was performed with the Sperman test,
      because our data were not normally distributed as tested by the Kolmogorov
      Smirnov test (p < 0.01). RESULTS: The median values of penile dimensions recorded
      in the present study are flaccid length 9.0 cm, flaccid circumference, at the
      middle of the shaft, 10.0 cm, and stretched length 12.5 cm. We also observed that
      the penile dimensions are highly correlated with height and weight. CONCLUSIONS:
      Since penile length and circumference correlate with anthropometric parameters
      such as weight and height, we suggest to consider themselves as two bodily
      measures which display a wide extent of normal variability along the general
      population.

PMID- 11223677
TI  - Photodynamic diagnosis with 5-aminolevulinic acid in the treatment of secondary
      urethral tumors: first in vitro and in vivo results.
AB  - OBJECTIVES: Photodynamic diagnosis (PDD) is able to detect dysplasia and
      transitional cell cancer of the bladder. We report our first experiences using
      PDD in the urethra. MATERIALS AND METHODS: Three patients with secondary
      transitional cell cancer of the urethra were treated by using PDD. 5
      Aminolevulinic acid (ALA) was applied in a mixture with lubricant to achieve long
      enough contact with the urothelium. Negative effects were tested in vitro on
      three bladder cell lines. RESULTS: In vitro assays showed no enhanced negative
      effects on the viability of bladder cells using the combination of ALA/lubricant
      and medium in comparison to lubricant/medium alone. All patients showed markedly
      fluorescent areas, which were resected. The treatment was well tolerated without
      side effects attributable to the photosensitizer containing lubricant.
      CONCLUSION: Lubricant with ALA forms a viscous solution, which can successfully
      be used for PDD in the urethra. Thus marking tumors by fluorescence may improve
      transurethral resection and thus preserve the urethra.

PMID- 11223679
TI  - Treatment of renal stones by extracorporeal shockwave lithotripsy: an update.
AB  - AIM: Despite the extensive experience with minimal invasive stone therapy, there
      are still different views on the ideal management of renal stones. MATERIALS AND
      METHODS: Analysis of the literature includes more than 14,000 patients. We have
      compared these data with long-term results of two major stone centers in Germany.
      The results have been compared concerning the anatomical kidney situation, stone
      size, stone localization and observation time. RESULTS: According to the
      importance of residual fragments following extracorporeal shock wave lithotripsy
      (ESWL), we have to distinguish between clinically insignificant residual
      fragments and clinically significant residual fragments (CIRF). 24 months
      following ESWL stone passage occurs as a continuous process, and if there are no
      clinical symptoms, any endoscopic procedure should be considered as
      overtreatment. According to these results, stone-free rates of patients increase
      in longer follow-up periods. Newer ESWL technology has increased the percentage
      of CIRF. CONCLUSION: We consider ESWL in most patients with renal calculi as
      first-line treatment, except in patients with renal calculi bigger than 30 mm in
      diameter.

PMID- 11223680
TI  - Shock wave lithotripsy treatment of radiolucent ureteric calculi with the help of
      contrast medium.
AB  - OBJECTIVE: Extracorporeal shock wave lithotripsy (SWL) treatment of radiolucent
      ureteric calculi (UC) is hampered by the reduced visibility of the stone.
      Intravenous contrast medium (IV-CM) administration may overcome this problem by
      indirectly depicting the localisation of the stone. However, IV-CM administration
      bears known risks. The aim of this study was to compare the clinical outcome
      after SWL in two representative groups of patients with either radiolucent or
      radio-opaque UC. METHODS: Two groups of patients, 156 with a radiolucent UC and
      203 with a radio-opaque UC, were assessed with regard to age, gender, treatment
      modalities, auxiliary measures, complications, stone properties and stone-free
      rate 3 months after treatment. RESULTS: Both groups were comparable with regard
      to epidemiology, treatment and clinical outcome. In both groups, stone-free rates
      were well within the percentages described by other investigators. There were no
      adverse reactions to CM. CONCLUSIONS: The clinical outcome of SWL treatment for
      radiolucent ureter stones does not differ from that for radio-opaque ureter
      stones. Being a non-invasive treatment, SWL with the help of IV-CM administration
      should be the first-line therapy for radiolucent ureter stones. Although
      awareness of possible adverse reactions to CM is mandatory, the risk remains
      small.

PMID- 11223681
TI  - Complications of the Mainz pouch II (sigma rectum pouch).
AB  - OBJECTIVE: The complications of the sigma rectum pouch were analyzed. METHODS: A
      total of 60 patients who underwent a construction of the Mainz pouch II was
      analyzed retrospectively. Data on early complications was available for all
      patients, while long-term follow-up data was available for 50 patients. RESULTS:
      Perioperative mortality was nil. Early complications were encountered in 2 (3.3%)
      patients. Oral alkalizing supplementation therapy was required in 30 (60%) of the
      patients; 3 (6%) patients needed hospitalization for severe acidosis and
      hypokalemia. Hydronephrosis developed in 5 (5%) of 98 renoureteral units
      anastomosed. Acute pyelonephritis was observed in 3 (8%) patients. All of the
      patients were continent except for 1 female patient who had had previous
      radiotherapy to the pelvis. The mean voiding frequency during the day and night
      was 5.1+/-1.1 and 1.9+/-0.7, respectively. The psychological state and general
      health of 2 patients became progressively worse until they died of probable
      malnutrition and metabolic abnormalities. Mechanical bowel obstruction developed
      in 1 patient 2 years after surgery. CONCLUSION: The complication rate of the
      Mainz pouch II appears to be acceptable with a median follow-up of 31 months.
      Patient selection and cooperation are of paramount importance for a successful
      outcome.

PMID- 11223682
TI  - The issue of prophylactic antibiotics prior to flexible cystoscopy.
AB  - OBJECTIVE: The aim of this study was to determine whether single-dose parenteral
      antibacterial therapy significantly alters the rate of infection in patients
      undergoing flexible cystourethroscopy. PATIENTS AND METHODS: 162 patients were
      studied prospectively having either received parenteral antibacterial
      chemoprophylaxis prior to flexible cystourethroscopy or not. Pre- and
      postprocedure mid stream samples of urine (MSSU) were obtained to objectively
      evaluate the presence of infection. RESULTS: Gentamicin prophylaxis reduced the
      rate of post-cystoscopy-positive MSSUs from 21 to 5%. CONCLUSION: The
      surprisingly high rate of infection after flexible cystoscopy was significantly
      reduced by a single dose of gentamicin.

PMID- 11223683
TI  - Value of acute-phase proteins in the differential diagnosis of acute scrotum.
AB  - OBJECTIVES: The evaluation of patients with an acute scrotum is primarily based
      on physical examination, imaging studies, as well as blood and urine tests.
      However, the differential diagnosis may be difficult in some cases. In a
      retrospective study, we investigated the value of acutephase proteins in serum
      and plasma from patients with an acute scrotum. METHODS: A total of 104 patients
      (epididymitis n=52, testicular tumor n=17, testicular torsion n = 11, other
      conditions n = 24) with an acute scrotum were included in this study. In all
      patients the acute-phase proteins C-reactive protein (CRP), haptoglobin, alpha1
      acid glycoprotein and transferrin in serum as well as fibrinogen in plasma were
      determined by turbidimetric analysis. The results were compared to the clinical
      findings, routine blood and urine tests and ultrasound. RESULTS: Patients with an
      epididymitis showed at least a 4-fold elevation of CRP except for 2 cases (median
      63.2 mg/l). In these patients, the sensitivity of CRP was 96.2%, the specificity
      94.2%, the negative predictive value 94.2% and the positive predictive value
      94.3%. Patients with a testicular tumor had no significant elevation of CRP
      (median 9 mg/l) as well as those with a testicular torsion (median 5 mg/l) except
      for 1 patient. The difference between patients with epididymitis and those with
      noninflammatory conditions was statistically significant (p<0.001, Kruskal-Wallis
      test and Tukey-Kramer test). The remaining parameters (haptoglobin, fibrinogen,
      a1-acid glycoprotein, transferrin, white blood count, body temperature and
      ultrasound) were less sensitive and specific. CONCLUSIONS: Acute-phase proteins
      (especially C-reactive protein) are helpful in differentiating epididymitis from
      noninflammatory conditions like testicular torsion or tumor. Turbidimetric
      analysis of these proteins is rapid, easy and inexpensive.

PMID- 11223684
TI  - Branching activity in the human prostate: a closer look at the structure of small
      glandular buds.
AB  - OBJECTIVE: Knowledge regarding cell biologic characteristics of small solid
      glandular buds in the prostate and their relationship with branching activity in
      the human prostate is still fragmentary. Our object was to demonstrate, on the
      basis of immunophenotype, loci that harbor the potential for branching activity
      within the adult human prostate. MATERIALS AND METHODS: Semiserial sectioning was
      performed on 13 adult prostates in an effort to identify structures in the
      prostate that could be considered foci of growth. Selected slides were stained
      with biomarkers for basal/luminal cells (keratins), proliferation (MIB-1),
      apoptosis inhibitor (bcl-2), intercellular adhesion (E-cadherin), and stromal
      epithelial interactions (tenascin-C). Results were compared with fetal and
      prepubertal human prostates and microdissected rat prostates. RESULTS: Five
      histologic epithelial structures were identified in 19 paraffin blocks, which on
      serial sectioning showed morphologic transitions with a common pattern,
      consisting of reduction in number and caliber of acini until small solid buds of
      epithelial cells were reached. Immunophenotypically, the small solid glandular
      buds had a basal-cell keratin phenotype, expression of bcl-2 in virtually all
      cells, high proliferative activity, prominent intracellular localization of E
      cadherin, and enhanced periglandular tenascin-C immunoreactivity. The budding
      tips in fetal and prepubertal prostates revealed an immunostaining pattern
      identical to the small solid glandular buds in the adult, but different to the
      rat prostate. CONCLUSIONS: Our data suggest that dispersed small solid glandular
      buds have a capacity for growth, and as such may be considered foci of resumed
      reawakening branching activity with in the adult human prostate.

PMID- 11223685
TI  - Primary lymphoma of the penis: diagnosis and treatment.
AB  - A rare case of primary penile B cell non-Hodgkin's lymphoma is reported. We
      reported on 75-year-old man with primary penile lymphoma with consideration of
      the diagnosis and the various therapeutic approaches. We treated this case with
      local radiotherapy and systemic chemotherapy with good cosmetic and functional
      results. There was absence of recurrence 42 months after therapy.

PMID- 11223686
TI  - Simultaneous diagnosis of a metanephric adenoma and a clear cell carcinoma of the
      contralateral kidney.
AB  - Metanephric adenoma of the kidney is a rare, newly recognized entity of a unique
      benign renal tumor. Clinically, pain, hematuria and palpable mass are the most
      common presenting signs. Females predominate by well over 2:1. A higher incidence
      of polycythemia is often found in these patients. Only a few cases of this type
      of adenoma have been reported in the literature. We report on a 78-year-old
      female patient with a metanephric adenoma of the left kidney, which showed
      typical clinical, radiologic, microscopic and immunohistochemical findings. A
      clear cell carcinoma of the contralateral kidney was also discovered and treated.

PMID- 11223688
TI  - Radical retropubic prostatectomy using endoscopic gastrointestinal anastomosis
      staplers.
AB  - OBJECTIVE: To investigate whether the use of the endoscopic gastrointestinal
      anastomosis (GIA) stapler for hemostasis of the dorsal vein complex during
      radical retropubic prostatectomy saves operation time and blood loss together
      with therapeutic efficacy. MATERIALS AND METHODS: From April 1990 to December
      1998, a total of 296 patients underwent radical retropubic prostatectomy for
      prostate cancer in clinical stages T1, T2 and T3. In 157 patients we evaluated
      the efficacy of the endoscopic GIA stapler in order to minimize blood loss from
      the dorsal vein complex and to reduce mean operative time. RESULTS: The mean
      total operative time decreased an average of 35 min and the mean blood loss fell
      from 850 to 400 cm(3) using the stapling technique. Although complications are
      seen with traditional methods, we noted a net increase in anastomotic strictures
      with this new technique. CONCLUSIONS: Even if this technical trick is effective
      in reducing blood loss, a higher incidence of anastomotic strictures has to be
      taken into account when using staplers close to the anastomotic site.

PMID- 11223689
TI  - Antiandrogen withdrawal in the treatment of hormone-relapsed prostate cancer:
      single institutional experience.
AB  - OBJECTIVES: Locally advanced and metastatic prostate cancer eventually progresses
      in spite of complete androgen blockade. Second-line therapy is usually
      disappointing, and further progression is the rule. Laboratory and clinical data
      have indicated that antiandrogen withdrawal may be a valuable strategy in the
      treatment of these patients. However, after antiandrogen withdrawal,
      controversial clinical results have been reported. Therefore every contribution
      to this therapeutic strategy is useful. METHODS: Herein we present our experience
      with antiandrogen discontinuation in a series of 44 patients with locally
      advanced or metastatic prostate cancer treated with complete androgen blockade
      (CAB). RESULTS: Prostate-specific antigen (PSA) decline was observed in 13 of 44
      (29%) and in 11 of these patients the reduction was greater than 50%. No response
      or further progression after antiandrogen withdrawal was observed in 31 of the 44
      patients (71%). Among these patients 14 died due to prostate cancer after a mean
      period of 5.6 months. No patient in the responding group has died. CONCLUSIONS:
      Our data indicate that approximately 30% of patients with advanced prostate
      cancer treated with CAB respond to antiandrogen withdrawal with a reduction in
      serum PSA levels. Even though it is not clear whether this PSA reduction produces
      a benefit in terms of survival, we feel that antiandrogen withdrawal must be the
      first therapeutic maneuver in patients with advanced prostate cancer who progress
      after CAB. If there is no PSA response within 4 months, second-line treatment is
      necessary.

PMID- 11223691
TI  - Colonic metaplasia in the long-term follow-up of the ileal neobladder.
AB  - OBJECTIVE: To look for the presence of colonic metaplasia (CM), the shifting from
      sialomucins (SIs) to sulfomucins (SUs), considered as a probably premalignant
      lesion in the stomach in the mucosa of the ileal neobladder (IN). METHODS: 19
      patients with IN were subjected to endoscopic biopsy; the samples were analyzed
      by means of histochemistry with high iron diamine, a test indicated to identify
      SIs and SUs. RESULTS: CM was never observed earlier than 1 year after the
      operation, was absent in 9/19 patients (mean follow-up 14 months) and present in
      10/19 (mean follow-up 59 months). CONCLUSION: Time-dependent phenotypic changes,
      already described in the stomach as being premalignant, take place after constant
      contact with urine in the mucosa of the IN. It is at present unclear whether they
      may be defined as only metaplastic or frankly preneoplastic; anyway, a careful
      follow-up remains indicated in all patients with intestinal urinary diversions.

PMID- 11223690
TI  - High-dose epirubicin in the prophylactic treatment of T1G2 superficial bladder
      tumors.
AB  - OBJECTIVES: To evaluate the activity and safety of intravesical instillations of
      80 mg epirubicin in a selected patient population with T1G2 primary and multiple
      superficial bladder tumors. To assess the completeness of the transurethral
      resection (TUR) at 4 weeks (second look) and to compare the histology of local
      and review pathology. METHODS: One hundred and sixty-nine patients have been
      histologically assessed both locally and extramurally for T1G2 superficial
      bladder tumors. Epirubicin (80 mg/instillation) started within 20 days after TUR
      was administered weekly during the first month and then monthly for another 11
      months. Assessments for relapse were carried out according to the standard
      methods. RESULTS: Histological consistency for T1G2 between local and extramural
      assessments was found in 85.2% of cases. At the median follow-up time of 38
      months, the overall relapse rate was 43.3%. Treatment was very well tolerated: no
      systemic adverse events were reported and local adverse events were confined to
      chemical cystitis which in 3% required treatment discontinuation. CONCLUSIONS:
      Epirubicin (80 mg/instillation) appeared effective in the prophylaxis of relapse
      in primary and multiple T1G2 superficial bladder tumors. A second TUR at 3-4
      weeks is necessary in T1 tumors. Excellent concordance between local and review
      pathology was found.

PMID- 11223692
TI  - 980-nm diode laser treatment for recurrent urethral strictures.
AB  - OBJECTIVES: Our experience with laser treatment of urethral strictures with a 980
      nm diode laser is reported. METHODS: 45 consecutive patients with relapsing
      urethral strictures (mean age 65, range 25-85 years) were treated between
      February 1995 and February 1998. The fibrous and scar tissue was cut and
      vaporized at the 6 o'clock position with the laser beam. RESULTS: 44/45 patients
      were available for follow-up at 1 year and 32/43 at 2 years. At 12 months the
      average peak flow rates of the patients was 18 ml/s, and at the second year
      assessment it was 15.5 ml/s. Of the patients 21/44 (47.7%) were extremely
      satisfied (0-1 of the quality-of-life, QoL, assessment index) with the procedure,
      14/44 (31.8%) were satisfied (2 of the QoL assessment index), and 9/44 (20.4%)
      were not satisfied (> or = 3 of the QoL assessment index) due to the low flow
      rate or the recurrence of the stricture. (The sum of the first two categories is
      79.5%.) At the second year assessment the percentage of satisfied patients
      reached 78%, with 71% of the patients stable without any dilatation. CONCLUSIONS:
      Usually in recurrent strictures of the urethra open surgery is suggested, but we
      believe that there is still a place for endoscopy. With the laser we can make an
      incision at the 6 o'clock position without significant bleeding, very easily
      opening the urethra. We had 79.5 and 71% good results at the 1- and 2-year
      assessments (mean peak flow rate of 18 and 15.5 ml/min), respectively. To date,
      no definitive conclusions can be drawn, but we believe that laser treatment is
      indicated for recurrent strictures in high risk or elderly patients and in those
      who demand a minimally invasive procedure.

PMID- 11223693
TI  - Horseshoe-shaped marlex mesh for the treatment of pelvic floor prolapse.
AB  - OBJECTIVE: Pelvic prolapse results from weakness or damage to the normal pelvic
      support systems. The main support for the pelvic viscera is provided by the
      pelvic fascia, which is naturally reinforced by urethra-pelvic ligaments,
      cardinal ligaments and uterosacral ligaments. A polypropylene mesh (Marlex-Bard)
      was used as a genitourinary and rectal support in order to substitute the damaged
      pelvic fascia. METHODS: Sixteen consecutive females suffering from severe
      genitourinary prolapse entered the study. Using the HWS (Baden-Walker)
      classification 10 patients presented a grade-IV and 6 patients a grade-III
      cystocele, 7 patients a grade-III and 1 a grade-IV rectocele. Hysterocele of
      grade IV was present in 2 patients and in 5 patients grade III. No enterocele was
      present at the pre-operative visit. Twelve patients suffered from stress
      incontinence; one had obstructive urinary symptoms with postvoiding residual
      urine of >200 ml. All patients underwent urodynamic tests and pre-operative
      cystography. The primary aim was prolapse reduction and continence. The
      operation, under general anesthesia, consisted of insertion and fixation of a
      horseshoe-shaped Marlex mesh between pubis and sacrum to close the area between
      the pelvic viscera and inferior pelvic hiatus. Three patients underwent
      hysterectomy. RESULTS AND CONCLUSIONS: The follow-up ranged between 12 and 29
      months. In 15 patients the prolapse was completely resolved and 13 were dry at
      follow-up. One patient presented a complete recurrence at the 3-month follow-up.
      Nine cases of pre-operative constipation were recovered after surgery. This
      technique seems to give promising results in the repair of genitourinary prolapse
      and stress incontinence.

PMID- 11223694
TI  - Androstanolone treatment for congenital penile curvature.
AB  - OBJECTIVES: To test the etiological hypotheses of congenital penile curvature
      (CPC) and to infer the possible therapeutic approaches. MATERIALS AND METHODS:
      Seventy patients affected by CPC were enlisted for the present study: 37 with
      left curvature, 21 with ventral curvature, 11 with left ventral-lateral
      curvature, and 1 with right curvature. All patients under the age of 21 years
      were encouraged to take local medical therapy with alcohol androstanolone gel in
      a dosage of 0.15 mg/cm(2) of surface area. Group A (17-43 years of age) consisted
      of patients who refused medical therapy and decided to solve their problem with
      surgery. They underwent Nesbit's operation and were given a contralateral biopsy
      of the tunica albuginea at the same time. Cytoplasmic androgen receptors (CARs)
      were quantified in the tunica albuginea of both cavernous bodies (CBs). Group B
      consisted of 26 patients aged between 4 and 21 years who were given local medical
      therapy with androstanolone in alcohol gel. They underwent a maximum of 3 therapy
      cycles each lasting 2 months with a 1-month suspension between each. Group C
      consisted of 9 patients (27-53 years of age) who were fathers of 9 group B
      patients. These adults were also affected by penile curvature and taken into
      consideration as a control group because we have observed three spontaneous
      corrections of penile curvature in puberty. RESULTS: CARs research in group A and
      in 6 group B patients under the age of 20 revealed a 2-5 times reduction on the
      concave part of the cavernous body compared to the contralateral one. This
      difference progressively decreased in older patients. In group B, 14 patients
      aged between 4 and 15 years and 1 aged 17 (53.8%) were treated with a local
      androstanolone therapy and the result was a regression in the curvature between
      30 and 100%. Another 9 patients aged between 17 and 21 years did not show any
      improvement despite androstanolone treatment. CONCLUSIONS: The results show a 2-5
      times reduction in CARs on the hypoplastic cavernous body of young male patients.
      These differences progressively decreased in older patients. The positive results
      of the androstanolone therapy in patients under the age of 15 and the negative
      ones in older patients are certainly related to the quantity of CARs present on
      the tunica albuginea.

PMID- 11223695
TI  - Effect of potential renal acid load of foods on calcium metabolism of renal
      calcium stone formers.
AB  - OBJECTIVES: Diet has been proposed as a causative factor of hypercalciuria in
      patients with calcium stones. The aim of this study was to investigate the
      influence of diet on calcium metabolism of renal stone formers. METHODS: Thirty
      five renal calcium stone formers were entered in this study. A 2-day recall of
      dietary intake was obtained from each subject. The food records were coded and
      computer analyzed for total energy, protein, fat, carbohydrate, sodium,
      potassium, calcium, magnesium, phosphate, oxalate, vitamin C and fiber. Daily
      potential renal acid load (PRAL) of the diet was calculated considering the
      mineral and protein composition of foods, the mean intestinal absorption rate for
      each nutrient and the metabolism of sulfur-containing amino acids. A fasting
      blood sample was drawn and a 24-hour urine collection were obtained for analyses
      of calcium, phosphate and creatinine. Serum osteocalcin was also analyzed. A
      fasting 2-hour urine sample was collected in the morning for hydroxyproline,
      pyridinium cross-links and creatinine. RESULTS: The mean daily dietary PRAL of
      renal stone formers was 22.4 +/- 15.7 (range 4.2-65.8) mEq/day. Regression
      analysis demonstrated that urinary calcium excretion is dependent on daily
      protein intake and dietary PRAL, whereas the urinary pyridinium cross
      links/creatinine ratio is inversely dependent on daily calcium intake. The
      urinary pyridinium cross-links/creatinine ratio was significantly lower in
      patients on a low calcium diet (< 600 mg/day) than in other patients (19.5 +/-
      7.8 vs. 27.3 +/- 7.5 nM/mM, p = 0.008). No significant difference was observed
      between the 2 groups for daily urinary calcium (254 +/- 109 vs. 258 +/- 140
      mg/day), serum osteocalcin (8.2 +/- 3.3 vs. 6.2 +/- 2.4 ng/ml) and urinary
      hydroxyproline/creatinine (14.1 +/- 7.4 vs. 10.3 +/- 4 mg/g). CONCLUSIONS: The
      urinary calcium excretion of renal stone formers seems to be dependent on dietary
      acid load rather than dietary calcium intake. In patients consuming an acidifying
      diet a restriction of calcium intake could increase bone resorption leading to a
      progressive bone loss.

PMID- 11223696
TI  - Do we know everything about alpha-blockade in the management of lower urinary
      tract symptoms?
AB  - alpha(1)-Adrenoceptor antagonists such as tamsulosin relieve voiding and filling
      LUTS. Improvement of the voiding ('obstructive') symptoms is related to alpha(1A)
      related desobstruction. Improvement of the filling ('irritative') symptoms may be
      related to reduction of alpha(1D) (and alpha(1A))-related obstruction. Blockade
      of alpha(1A)-adrenoceptors in the human prostate may be required for reduction of
      obstruction and improvement of related voiding symptoms and urinary flow.
      Blockade of alpha(1D) (and alpha(1A))-adrenoceptors in the human bladder may, in
      addition, be required to relieve filling LUTS. These concepts should be evaluated
      further before definitive conclusions can be drawn. If definitely proven, this
      could mean that alpha-blockers have to be considered to not only act on BPH (the
      causative disease) but also (and perhaps more) on the target organ, the bladder.
      Early treatment could have a protective effect on the bladder and chronic
      treatment could prevent hypertrophic bladder modification.

PMID- 11223697
TI  - Pseudomyxoma peritonei: a review of current literature.
AB  - Pseudomyxoma peritonei is an unusual condition more common in females, in which
      massive amounts of mucinous ascites in conjunction with mucinous peritoneal and
      omental implants occur. We performed a MEDLINE search of the English-language
      literature from 1966 to June 2000, utilizing the key words pseudomyxoma
      peritonei. All case reports, series and studies regarding this condition were
      reviewed. Cross-referencing was also performed. The etiology and treatment of
      this condition are currently controversial. Most investigators agree that
      surgical debulking and appendectomy are adequate initial therapeutic measures.
      The role of intraperitoneal chemotherapy, radiotherapy or application of
      mucolytic therapy remains uncertain. Recent molecular genetic studies suggest the
      appendix as the organ of primary origin of this disease.

PMID- 11223698
TI  - Uptake and protection against oxidative stress by estrogen esters in THP-1 human
      macrophage cell lines.
AB  - Estrogen replacement therapy offers protection from coronary artery disease in
      postmenopausal women. However, there is serious concern that long-term unopposed
      estrogen use increases the risk of breast and endometrial cancer through estrogen
      receptor-driven mechanisms. In this communication, we have explored an alternate
      route of estrogen delivery to macrophages using hydrophobic derivatives that
      associate with lipoproteins. Unlike free estradiol (E(2)), long-chain fatty acid
      esters of E(2) associate extensively with low-density lipoprotein (LDL). In THP-1
      cells, E(2) esters accumulated to a significantly higher level when compared to
      E(2) in the presence of LDL. In the presence of oxidized LDL even greater amounts
      of E(2) esters accumulated in cells. In THP-1 cells, E(2) esters were capable of
      preventing the azo-bis-induced increase in oxidative stress (hydrogen peroxide
      formation). These studies suggest that (a) hydrophobic esters of estrogens that
      associate with LDL can be delivered to macrophages and (b) these esters can
      effectively function as antioxidants protecting against oxidative stress.

PMID- 11223699
TI  - Observed versus expected rates of unbalanced fetal karyotype at second trimester
      amniocentesis when one parent carries a balanced translocation.
AB  - Our purpose is to evaluate a model proposed by Stene et al. for estimating the
      risk of unbalanced progeny at the time of second trimester amniocentesis for 114
      pregnancies of 71 couples, who are carriers of a reciprocal translocation. The
      overall estimated risk was 18%, 1.26 times higher than the observed risk (14%).
      There were no unbalanced fetuses in the 19 pregnancies of the no-risk group. In
      the low-risk group, the observed risk was highly correlated with the estimated
      risk. However, the estimated risks in the medium- and high-risk groups were much
      higher than the observed risks (2- and 1.5-fold). In the group ascertained
      through spontaneous abortions, the average estimated risk was 1.9 times higher
      than the observed risk. Although the model is useful in estimating individual
      empirical risks, it may be necessary to consider the type of ascertainments and
      add some modifications to calculate the risks in the second trimester.

PMID- 11223700
TI  - Clinical evaluation of the Q-tip test in normal pregnant women.
AB  - The crisis frequency of stress incontinence (SI) is known to be high among
      pregnant women. This preliminary study was performed to determine whether the
      diagnostic standard of the Q-tip test used in the diagnosis of SI in nonpregnant
      women is applicable to pregnant women. The Q-tip tests were performed regularly
      during pregnancy and after parturition on primipara (n = 71) and multipara (n =
      55) who were not in SI crisis at any time during the pregnancy. The values
      measured in multipara were significantly higher than in primipara (p = 0.0001),
      and the tendency to be higher was more prominent at 2-5 months and 10 months of
      pregnancy. These findings show that different normal values of the Q-tip test are
      necessary for primipara and multipara.

PMID- 11223701
TI  - Plasma levels of soluble Fas during normal pregnancy.
AB  - The Fas/Fas ligand system could reportedly help to identify a mechanism for
      maternal immunotolerance of the fetus in human pregnancy. However, there are few
      reports on soluble Fas (sFas) which is an inhibitor of apoptosis during normal
      pregnancy. Therefore, ascertaining plasma sFas levels during pregnancy would be
      of interest. The subjects studied were 10 nonpregnant healthy women and 20
      healthy pregnant women in the first and third trimester with singleton
      gestations. The plasma sFas was measured by sandwich enzyme-linked immunosorbent
      assay. The mean concentration of sFas was significantly decreased in normal
      pregnant women in the first trimester compared to age-matched control subjects,
      and it did not differ significantly between normal pregnant women in the third
      trimester and age-matched control subjects. From these results, we presume that
      the decreased plasma sFas plays an important role in maternal immunotolerance in
      the first trimester of pregnancy.

PMID- 11223702
TI  - Pregnancy in women with epilepsy.
AB  - The aim of this study was to analyze the outcome of pregnancy and delivery in
      epileptic women. A retrospective review of the 41 pregnant women with epilepsy
      who delivered in the Department of Obstetrics and Perinatology of the University
      School of Medicine in Lublin over 7 years (1993-1999) was carried out. Women with
      epilepsy had more pregnancy complications including premature labor, anemia,
      hypertension, vaginal bleeding, urinary tract infection, nausea and vomiting. An
      increased risk of congenital malformations and intrauterine fetal growth
      retardation was observed. Women with epilepsy require more extensive pregnancy
      planning including neurologic and preconceptional care.

PMID- 11223703
TI  - Insulin response patterns contribute to different perinatal risks in gestational
      diabetes.
AB  - The aim of this study was to evaluate the insulin dynamics of patients with
      gestational diabetes mellitus (GDM) and to compare perinatal outcomes according
      to the insulin response patterns. Twenty-two out of 925 consecutive women
      examined were diagnosed as having GDM. One hundred and ten women who experienced
      a normal pregnancy were used as controls. Plasma glucose levels and insulin
      responses were evaluated by a 2-hour 75-gram oral glucose tolerance test (OGTT).
      Immunoreactive insulin (IRI), the area under the curve (AUC) of glucose (AUCg)
      and insulin (AUCi), and the insulinogenic index (II = DeltaIRI 30 min/DeltaBS 30
      min) were measured. The GDM patients were divided into three subgroups,
      consisting of hyper-, normo- and hypoinsulinemic groups, according to the mean +/
      2 SD of the AUCi obtained from the controls. Clinical and laboratory findings
      were compared among the GDM subgroups and controls. The GDM patients showed
      impaired insulin secretion to glucose stimuli, with low plasma insulin levels (at
      30 min) and reduced insulin/glucose ratios (at 30 and 60 min) early in the 75
      gram OGTT. The II and AUCi/AUCg values of GDM patients were reduced as compared
      with those of controls. These reduced insulin responses were remarkable in hypo-
      and normoinsulinemic GDM patients, but were not detected in hyperinsulinemic GDM
      patients. The number of babies large for their gestational age in normo- and
      hypoinsulinemic GDM patients was significantly higher than that in
      hyperinsulinemic GDM patients or controls. Hyperinsulinemic GDM patients had a
      high frequency of pregnancy-induced hypertension (40%). The body mass index prior
      to pregnancy of hyperinsulinemic GDM patients was significantly higher than that
      of normoinsulinemic GDM patients or controls. It was demonstrated that not only
      insulin secretion, but also perinatal clinical characteristics, differed among
      the GDM subgroups. The heterogeneity of the disease was thus confirmed.

PMID- 11223704
TI  - Serum nitric oxide and glutathione levels in preeclamptic and normotensive women
      during labor.
AB  - This study was performed on 38 preeclamptic women, including 26 severely
      preeclamptic and eclamptic cases, as well as 50 normotensive pregnant controls.
      Twenty cases in the preeclamptic group and 34 cases in the control group were in
      labor. Serum nitric oxide levels were measured as total nitrites after reduction
      of nitrates to nitrites. Among the control subjects, nitric oxide levels were
      significantly lower in the cases in labor when compared to those not in labor (p
      < 0.05), but glutathione levels were not significantly different (p >0.05). Among
      the preeclamptic patients, although nitric oxide levels were not significantly
      different between the cases in and not in labor (p > 0.05), glutathione levels
      were significantly higher in the latter group (p < 0.05). Thus, in preeclamptic
      patients there might be a compensatory increase in nitric oxide production during
      labor in order to maintain the systemic circulation. Glutathione levels might
      also be increased to compensate for the marked oxidative stress.

PMID- 11223705
TI  - Intrapartum prediction of macrosomia: accuracy of abdominal circumference
      estimation.
AB  - OBJECTIVE: To evaluate the accuracy of abdominal circumference (AC) estimation of
      macrosomia early in labor and whether a cutoff value could be detected. DESIGN: A
      prospective clinical trial. SETTING: The Department of Obstetrics and Gynecology,
      Cairo University. PARTICIPANTS: One hundred pregnant females presenting in early
      labor with clinical impression of macrosomia were examined by ultrasound, and
      those babies with abdominal circumference more or equal to 35 cm were recruited
      for the study. INTERVENTIONS: Every woman was considered as her own control, and
      fetal weight was calculated using the formula of Shepard et al. The accuracy of
      abdominal circumference in prediction of macrosomia was evaluated using the
      Receiver operating characteristic curve. RESULTS: A cutoff value of AC > or =37
      cm was found to have a sensitivity of 77%, a specificity of 75%, a positive
      likelihood ratio of 3.1 and a negative likelihood ratio of 0.3. CONCLUSION:
      Intrapartum ultrasonographic evaluation of abdominal circumference for suspected
      macrosomic babies in early labor is an easy, practical method that should be
      adopted in decision making.

PMID- 11223706
TI  - Low dose of ethinyl estradiol can reverse the antiestrogenic effects of
      clomiphene citrate on endometrium.
AB  - Fifty healthy, voluntary patients aged between 20 and 30 years with regular
      menstruation and plasmatic progesterone level >10 ng/ml at the midluteal phase
      have been enrolled in this study. They were randomly treated with clomiphene
      citrate (CC; group A) or CC + ethinyl estradiol (0.05 mg group B, or 0.02 mg
      group C). We estimated the difference in uterine artery pulsatily index,
      endometrial thickness and histological dating and morphometric analysis of
      endometrium. No significant differences in Pulsatility Index values and in the
      number of preovulatory follicles were noted. The difference between endometrial
      thickness, histological dating and morphometric analysis of the endometrium were
      statistically different between groups B and C vs. A. Our study shows that CC has
      a deleterious effect on endometrium maturity and that adding ethinyl-E(2)
      produces a favorable endometrial response even with very low doses.

PMID- 11223707
TI  - Regulation of human endometrial stromal decidualization by macrophage colony
      stimulating factor.
AB  - Decidualized human endometrial stromal cells and human decidual CD56+ cells are
      reported to produce macrophage colony-stimulating factor (M-CSF), although its
      physiological roles remain unclear. In this study, the effects of M-CSF on cell
      viability and 8-Br-cAMP-stimulated decidualization of normal human endometrial
      stromal cells are examined by using an in vitro decidualization activity assay
      system. M-CSF alone affected neither the viable cell numbers nor PRL release of
      nonstimulated stromal cells, while high concentrations of M-CSF strongly
      suppressed the viable cell numbers and PRL secretion of stromal cells
      costimulated with 8-Br-cAMP and M-CSF. However, M-CSF did not suppress the viable
      cell numbers and PRL secretion of 8-Br-cAMP-induced decidualized cells. These
      results indicate that high concentrations of M-CSF can suppress the cell
      viability of stromal cells in the decidualization process, and inhibit
      decidualization of endometrial stromal cells. Thus, nonpregnant decidual M-CSF
      may autoregulate decidualization and the viable cell numbers of endometrial
      stromal cells in a paracrine manner.

PMID- 11223708
TI  - Thermal balloon ablation in myoma-induced menorrhagia under local anesthesia.
AB  - OBJECTIVE: Our purposes were to compare the impact of surgery on menstrual blood
      flow reduction and on the increase in hemoglobin values as primary endpoints at
      12 months, and operating time, complication rates, postoperative pain scores at
      12 h and surgically induced amenorrhea rates at 12 months as secondary endpoints
      after roller ball endometrial ablation or thermal balloon ablation for myoma
      induced menorrhagia. MATERIALS AND METHODS: Menorrhagic women (documented by a
      validated pad scoring system) over 40 years of age, with a mobile myomatous
      uterus smaller than 12-week pregnancy, were enrolled in a prospective randomized
      trial to compare endometrial roller ball ablation and thermal balloon ablation
      after pharmacological endometrial thinning. One year after surgery, primary and
      secondary endpoints in both groups were compared. RESULTS: Forty-five subjects
      underwent endometrial thermal balloon ablation under local anesthesia and 48
      underwent endometrial roller ball ablation under general anesthesia.
      Statistically significant but similar decreases in mean pictorial blood
      assessment score and increases in mean hemoglobin values were noted for both
      groups at 12 months. Those who underwent endometrial roller ball ablation had
      experienced significantly more intraoperative complications. CONCLUSION: Thermal
      balloon ablation under local anesthesia for myoma-induced menor- rhagia provided
      both significant and statistically similar reductions in menstrual blood flow and
      increases in hemoglobin values with no intraoperative complication compared to
      roller ball endometrial ablation.

PMID- 11223709
TI  - Association between polycystic ovary and fibrocystic breast disease.
AB  - OBJECTIVE: The aim of this study was to assess whether or not there was an
      association between a polycystic ovary (PCO) and fibrocystic breast disease based
      on ultrasound findings, both pelvic and mammographic. DESIGN: Prospective case
      control study. POPULATION: Women aged between 18 and 30 years not using oral
      contraceptives attending the outpatient ultrasound clinic from January 1996 to
      December 1998. MAIN OUTCOME: Confirm the association between PCO and fibrocystic
      breast disease. RESULTS: According to the ultrasound findings, women were
      allocated to three groups: 351 out of 456 showed normal-appearing ovaries (group
      A), 93 had polycystic-appearing ovaries/PCO (group B) and 12 had PCO syndrome
      (group C). In group A, 24 (6.83%) women showed breast pathology. In group B,
      there was an association between PCO and breast pathology in 53 (56.98%) women,
      while in group C it was noted in 11 out of 12 (91%). CONCLUSION: This study
      showed a significant association between PCO and benign pathology. This should
      encourage the performance of a screening breast sonography on women with PCO.

PMID- 11223710
TI  - Transient bilateral osteoporosis of the hip in pregnancy. A case report and
      review of the literature.
AB  - Osteoporosis of the hip is a rare complication of pregnancy, the diagnosis of
      which can only be determined by radiologic means. Differentiation between
      osteonecrosis and osteoporosis remains problematic in some cases. Magnetic
      resonance imaging was reported as useful for the diagnosis of osteoporosis.
      Treatment of osteoporosis of the hip in pregnancy should be conservative
      including physical therapy, restricted weight bearing and analgetic therapy. We
      report an unusual case of bilateral transient osteoporosis of the hip in
      pregnancy.

PMID- 11223712
TI  - Magnetic resonance imaging in the preoperative determination of tumor
      resectability in previously irradiated groin tumor.
AB  - We present an unusual case in which magnetic resonance (MR) imaging was utilized
      in the preoperative determination of resectability of a large inguinal tumor. The
      patient had previously presented with a large fungating, surgically nonresectable
      mass, which impinged upon the anterior ramus of the pubic bone. Following
      chemotherapy and radiation, the mass appeared more mobile and surgically
      resectable. Due to fibrosis and induration, the relationship of the tumor and
      underlying femoral vascular bundle were unclear. MR imaging clearly depicted that
      the tumor was sufficiently distant from the vessels, to allow safe resection with
      an adequate surgical margin. Resection was performed with clear lateral and deep
      margins. Histopathology demonstrated squamous cell carcinoma of the inguinal skin
      replacing subcutaneous tissue.

PMID- 11223711
TI  - Antenatal three-dimensional sonographic features of Pierre-Robin syndrome. Case
      report.
AB  - A case of Pierre-Robin syndrome with polyhydramnios is described. Three
      dimensional sonography clearly showed fetal micrognathia and hypoplastic ear
      antenatally. The benefits and advantages of the use of three-dimensional
      sonography to diagnose Pierre-Robin syndrome in utero are discussed.

PMID- 11223713
TI  - Mice genetic immunization with plasmid DNA encoding a secreted form of HSV-1 gB
      induces a protective immune response against herpes simplex virus type 1
      infection.
AB  - Intramuscularly (i.m.) delivered plasmid DNA encoding a secreted form of
      glycoprotein B of herpes simplex virus type 1 (HSV-1 gB1s) was evaluated for the
      ability to elicit a protective immune response in Balb/c mice. Animals received
      three i.m. injections of a gB1s expression plasmid (pRP-RSV-gB1s) or of a wild
      type transmembrane gB1 coding plasmid (pRP-RSV-gB1), while control mice were
      injected with the vector alone (pRP-RSV). A specific antibody response was
      observed in almost all immunized animals, and in most cases antibodies were also
      detected after 1 month in the absence of further vaccine boosts. Serum antibodies
      mostly displayed neutralizing activity against HSV-1. Glycoprotein B1s DNA
      immunization was also effective in protecting animals against the primary
      infection induced by a subsequent HSV-1 challenge and limited HSV-1 infection of
      sensitive ganglia.

PMID- 11223714
TI  - Uptake of pp65 in in vitro generated pp65-positive polymorphonuclear cells
      mediated by phagocytosis and cell fusion?
AB  - OBJECTIVE: The cytomegalovirus (CMV) antigenemia consists of the detection of CMV
      pp65 in the nucleus of polymorphonuclear granulocytes (PMN), but it is unclear
      where and how PMN pick up virus particles or proteins. In an in vitro model for
      CMV antigenemia we investigated the mechanism of pp65 uptake by PMN that results
      in its expression in the nucleus. METHODS: A series of inhibitors of different
      mechanisms was used to study the uptake of pp65 by PMN during coculture with CMV
      infected endothelial cells and we performed a morphological analysis by light and
      transmission electron microscopy. RESULTS: Nocodazole and cytochalasin B
      inhibited uptake of pp65 by PMN with 59.4 +/- 14.1 and 73.3 +/- 12.7%,
      respectively. The presence of anti-CMV hyperimmune globulin or lactoferrin during
      coculture reduced the number of pp65-positive PMN with 45.8 +/- 7.0 or 40.6 +/-
      3.2%. Furthermore, a small number of the pp65-positive PMN obtained after
      coculture had fused to large cells with multilobed nuclei. PMN were observed that
      enclosed viral particles as well as free viral particles containing PMN in the
      cytoplasm. CONCLUSION: Fusion of viral particles with PMN and phagocytosis are
      both involved in the uptake of pp65.

PMID- 11223715
TI  - Detection of HGV RNA in digestive organs.
AB  - The organ where the GB virus (GBV)-C/hepatitis G virus (HGV) localizes and
      proliferates is not known. We examined the digestive organs for HGV RNA to
      determine the localization of the HGV. Two cases of patients with serum-positive
      HGV RNA were investigated. We embedded surgically excised materials and digestive
      secretion materials from cases 1 and 2 in paraffin blocks. The tissue specimens
      investigated included lymph nodes No. 201 and 202, ascending colon (nontumor and
      tumor area), ileocecum, appendix, liver (nontumor and tumor area) and gall
      bladder. We made cDNA after extraction of total RNA from thin tissue sections and
      detected HGV RNA with a reverse transcription polymerase chain reaction method.
      No HGV RNA was detected in liver, colon and gall bladder tissues. HGV RNA was
      only detected in the appendix tissue. Comparison of nucleotide sequences of PCR
      products from serum and appendix was almost the same. Homology between US type
      (PNF2161) and the serum and appendix PCR products was 92.6 and 93.6%,
      respectively. These results suggest that HGV proliferates in the appendix and is
      carried by the portal blood flow to the liver, and may cause a hepatitis reaction
      in the liver.

PMID- 11223716
TI  - Molecular dissection of hepatitis C virus expression.
AB  - OBJECTIVE: The 5' untranslated region (5' UTR) of the hepatitis C virus genome is
      thought to be important for the control of viral gene expression and a likely
      target for therapeutic interception. A functional role of this viral gene segment
      was analyzed both in vivo and in vitro. METHODS: Transgenic mice carrying a
      reporter gene that contains the complete 5' UTR sequence were made. Cellular
      protein(s) which associate with the 5' UTR were analyzed by gel shift analysis
      and a following affinity purification. RESULTS: Transgenic mice revealed protein
      accumulation only in periportal hepatocytes around the portal triad and not in
      perivenous hepatocytes around the central vein. Gel shift analysis using mouse
      liver extracts provides further evidence that trans-acting proteins, which
      recognize a specific cis-acting element with the 5' UTR (an apparent stemmed
      structure formed by two noncontiguous RNA sequences), are present in adult mice
      but not in young mice. A similar 5' UTR RNA-protein complex was also detected
      with human liver extracts. CONCLUSION: The presence of cellular factor(s) which
      allow HCV 5' UTR to express in tissue and differentiation state-specific manner
      was suggested.

PMID- 11223717
TI  - 121R protein from the E3 region of bovine adenovirus-3 inhibits cytolysis of
      mouse cells by human tumor necrosis factor.
AB  - Based on the DNA sequence and known mRNA structures, the early region 3 (E3) of
      bovine adenovirus (BAV)-3 has the potential to encode four proteins. One of them
      (121R) is produced as a 14.5-kD protein throughout infection. Analysis of the
      121R protein showed limited homology to a 14.7K protein of human adenovirus (HAV)
      5. Interestingly, both anti-14.7K and anti-121R sera immunoprecipitated a 14.5-kD
      protein from cells infected with BAV-3. To determine if 121R is functionally
      related to 14.7K, we constructed a recombinant E3-deleted HAV-5 (AdKV121)
      expressing the BAV-3 E3 121R protein. Mouse C3HA cells infected with HAV-5 mutant
      dl 758 (deletion of 14.7K) were sensitive to TNF lysis. However, wild-type HAV-5-
      or recombinant AdKV121-infected cells were resistant to TNF-induced cytolysis.
      Our result show that the BAV-3 E3 121R protein is serologically and functionally
      related to the 14.7K protein encoded by the E3 region of HAV-5.

PMID- 11223718
TI  - Detection of serum and intrahepatic human hepatocyte growth factor in patients
      with type C liver diseases.
AB  - We determined hepatocyte growth factor (HGF) levels in the serum and liver of
      patients with hepatitis C and assessed the relationship to histological findings
      of the liver and hepatitis C virus-related markers in the serum in patients with
      type C liver diseases. The subjects were 108 patients with chronic hepatitis C
      (CH), 70 patients with liver cirrhosis C (LC), 38 patients with hepatocellular
      carcinoma (HCC) and 20 patients with acute hepatitis (AH). As normal controls 20
      subjects were studied. The serum HGF levels were measured using an enzyme-linked
      immunosorbent assay kit. Intrahepatic HGF was investigated by immunoperoxidase
      staining using monoclonal HGF antibody. The serum HGF level was highest in
      patients with AH. The serum HGF levels tended to be higher in patients with LC
      and HCC than those with CH. Further, the serum HGF level was related to the
      degree of intrahepatic inflammatory cell infiltration and fibrosis, and
      intrahepatic HGF was noted primarily in the cell membrane of mesenchymal cells in
      focal necrosis. The degree of intrahepatic HGF expression tended to be higher in
      patients with high serum HGF levels. In patients with HCC, however, HGF showed
      little localization in cancer cells, but was noted in infiltrating mesenchymal
      cells in both cancerous and noncancerous regions. In conclusion, the measurement
      of serum HGF levels may be useful for estimating the degree of intrahepatic
      inflammatory reaction and fibrosis. Although further study is necessary, the high
      serum level of HGF revealed high carcinogenic states in chronic hepatitis and
      liver cirrhosis type C.

PMID- 11223719
TI  - Hepatitis B virus genotype distribution among chronic hepatitis B virus carriers
      in Shanghai, China.
AB  - OBJECTIVE: Hepatitis B virus (HBV) genotype distribution is still unclear in
      China, where a high prevalence of HBV infection exists, although it is well known
      that HBV can be classified into six genotypes based on intergroup divergence. The
      aim of this study was to investigate the epidemiological distribution of HBV
      genotypes and to clarify further the genotype-related differences in the
      pathogenicity of HBV. METHODS: Seminested PCR and restriction fragment length
      polymorphism analysis were conducted in 97 asymptomatic HBV carriers (ASC) and 46
      chronic hepatitis (CH), 37 liver cirrhosis (LC) and 44 hepatocellular carcinoma
      (HCC) patients in Shanghai, China. RESULTS: Two hundred and twenty samples
      (98.2%) were positive for HBV DNA, and of these, 3 (1.4%), 38 (17.2%) and 179
      (81.4%) were classified as genotype A, B and C, respectively. There was a
      statistically significant difference in the distribution of genotypes B and C
      among various categories of liver diseases (p < 0.01). The distribution of
      genotype C showed an increasing trend from ASC, CH and LC to the HCC group; in
      contrast, the distribution of genotype B showed a decreasing trend in the same
      order. HBeAg positivity was higher in genotype C than in genotype B in all the
      subjects or in the ASC group alone (p < 0.05, p < 0.01, respectively). More
      severe liver damage and a higher mean age were observed in genotype C than in
      genotype B (p < 0.01, p < 0.05, respectively). CONCLUSIONS: These results
      indicate the following: (1) genotypes A, B and C of HBV exist in Shanghai, China;
      (2) genotype C is the major genotype in this area; (3) genotype C is associated
      with the development of severe liver diseases, and (4) genotype B has a
      relatively good prognosis.

PMID- 11223720
TI  - Electron microscopic study of persistent dengue virus infection: analysis using a
      cell line persistently infected with Dengue-2 virus.
AB  - We investigated persistent infection of Epstein-Barr virus (EBV)-transformed
      lymphoblastoid cells with dengue virus using a transmission electron microscope.
      Most of the infected cells kept an intact morphology with only a few virus
      particles in the cytoplasm, but without any indication of active viral
      replication. Some cells were apoptotic and a few dengue virus particles were
      present in these apoptotic cells. Raji cells acutely infected with dengue-2 virus
      showed degenerative morphology. There were membranous tubular structures and many
      virus particles around and within the infected cells. Approximately 95% of the
      cells were dengue viral antigen positive in the persistently infected EBV
      transformed cell line. It is likely that persistent infection is maintained
      mainly by the division of infected cells without cytopathic effect by dengue-2
      virus.

PMID- 11223721
TI  - BHRF1 is highly conserved in primate virus analogues of Epstein-Barr virus.
AB  - The Epstein-Barr virus (EBV) protein BHRF1 (BamHI rightward reading frame 1) was
      the first viral member of the Bcl-2 family of apoptosis-regulating proteins
      described. In vitro studies imply that BHRF1 is dispensable for virus-induced
      cellular transformation and virus replication. However, in contrast to several
      essential viral genes that show divergence outwith their functional domains,
      sequence data from a wide range of EBV isolates show there is striking
      conservation of the BHRF1 gene. Contrary to the in vitro studies, the high degree
      of conservation hints at a more important role for BHRF1. Analogous viruses are
      endemic in each of the higher primate species. Whilst their genome organisation
      is colinear, limited sequence analysis indicates that the viruses have diverged
      significantly and that only important functional domains of proteins are likely
      to be conserved. We have isolated the BHRF1 equivalents from the viruses which
      infect chimpanzees (Herpesvirus pan) and baboons (Herpesvirus papio) and find
      that they are highly homologous in both species, strengthening the hypothesis
      that BHRF1 plays a significant, evolutionarily conserved function in vivo and
      that changes to the protein are not well tolerated.

PMID- 11223723
TI  - A world galloping into breathlessness.

PMID- 11223724
TI  - Epidemiology of chronic obstructive pulmonary disease (COPD).
AB  - Chronic Obstructive Pulmonary Disease (COPD) is one of the leading causes of
      morbidity and mortality in the industrialized and the developing countries.
      During 1997, COPD has been estimated to be the number four cause of death after
      cardiovascular diseases, tumors and cerebrovascular diseases in the United
      States. In 2020 COPD will probably become the third leading cause of death all
      over the world, following the trend of increasing prevalence of lung cancer. The
      impact of this respiratory disease worldwide is expected to increase with a heavy
      economic burden on individuals and society. In the United States direct and
      indirect costs of COPD were estimated at about USD24 billion in 1993.
      Unfortunately, there are few data on health-care utilization despite the great
      interest in COPD among researchers. As all chronic diseases, the prevalence of
      COPD is strongly associated with age. Data collected in a general population
      sample (living in Italy) showed a progressive increase of the prevalence of
      chronic bronchitis and emphysema with age, both in males and in females. COPD is
      determined by the action of a number of various risk factors either singly or
      interacting among themselves in a synergistic way. Among these, the most
      important is cigarette smoking, ranking at the first level for developing chronic
      bronchitis and emphysema. Also air pollution and some occupational exposures
      represent risks for developing COPD. Many epidemiological studies have indicated
      an association between the prevalence of chronic bronchitis and a low
      socioeconomic status. Furthermore, in the etiology of COPD we must consider
      endogenous risk factors such as gender, genetic features, presence of respiratory
      troubles in childhood, and family history. To date, epidemiologic studies have
      been of great importance for the characterization of the disease at a population
      level, indicating possible causes and assessing its impact on the individual and
      on society as a whole. Unfortunately, international standards for the diagnosis
      of COPD are lacking, which complicates the organization of appropriate
      epidemiological surveys.

PMID- 11223725
TI  - The price of modern medicine: are we willing to pay it?

PMID- 11223726
TI  - Assessment of maximum inspiratory pressure. Prior submaximal respiratory muscle
      activity ('warm-up') enhances maximum inspiratory activity and attenuates the
      learning effect of repeated measurement.
AB  - BACKGROUND: The variability of maximal inspiratory pressure (PImax) in response
      to repeated measurement affects its reliability; published studies have used
      between three and twenty PImax measurements on a single occasion. OBJECTIVE: This
      study investigated the influence of a specific respiratory 'warm-up' upon the
      repeated measurement of inspiratory muscle strength and attempts to establish a
      procedure by which PImax can be assessed with maximum reliability using the
      smallest number of manoeuvres. METHODS: Fourteen healthy subjects, familiar with
      the Mueller manoeuvre, were studied. The influence of repeated testing on a
      single occasion was assessed using an 18-measurement protocol. Using a randomised
      cross-over design, subjects performed the protocol, preceded by a specific
      respiratory warm-up (RWU) and on another occasion, without any preliminary
      activity (control). Comparisons were made amongst 'baseline' (best of the first 3
      measurements), 'short' series (best of 7th to 9th measurement) and 'long' series
      (best of the last 3 measurements). RESULTS: Under control conditions, the mean
      increase ('baseline' vs. 'long' series) was 11.4 (5.8)%; following the RWU, the
      increase (post RWU 'baseline' vs. 'long' series) was 3.2 (10.0)%. There were
      statistically significant differences between measurements made at all 3 protocol
      stages ('baseline', 'short' and 'long' series) under control conditions, but none
      following the RWU. CONCLUSIONS: The present data suggest that a specific RWU may
      attenuate the 'learning effect' during repeated PImax measurements, which is one
      of the main contributors of the test variability. The use of a RWU may provide a
      means of obtaining reliable values of PImax following just 3 measurements.

PMID- 11223727
TI  - Measurement of gastric P(CO2) as an index of tissue hypoxia during obstructive
      sleep apnea.
AB  - BACKGROUND: Gastric mucosal ischemia develops in critically ill patients in a
      number of clinical settings due to diversion of blood flow from the splanchnic
      bed to more vital organs, and can be detected by the measurement of gastric
      intramucosal pH (pHi). STUDY OBJECTIVE: We hypothesized that similar changes
      would occur during obstructive sleep apnea (OSA) due to increased respiratory
      work during the periods of apnea. METHODS: Gastric P(CO2), pHi and arterial blood
      gases were measured during 3 conditions in 8 patients with severe OSA: at
      baseline awake, while asleep with > or = 30 obstructive apneas or hypopneas per
      hour, and asleep after elimination of apneas with continuous positive airway
      pressure (CPAP). RESULTS: Significant changes between the baseline and apnea
      conditions were detected using ANOVA for repeated measures for gastric P(CO2),
      40.2 +/- 5.3 vs. 85.4 +/- 34.0 (p < 0.001), pHi, 7.41 +/- 0.06 vs. 7.11 +/- 0.17
      (p < 0.005), and the gastric-arterial P(CO2) difference (D(CO2)), -2.3 +/- 5.5
      vs. 44.3 +/- 36.21 (p < 0.006). Nasal CPAP returned all measures back to baseline
      values. CONCLUSIONS: Gastric tissue hypoxia develops in patients with severe OSA
      and may be a marker of disease severity. Treatment of OSA with CPAP eliminates
      the regional tissue hypoxia.

PMID- 11223729
TI  - Bronchial hyperresponsiveness and exhaled nitric oxide in patients with cardiac
      disease.
AB  - BACKGROUND: Increased concentrations of exhaled nitric oxide (NO) correlate with
      increased airway inflammation and measurement of exhaled NO is a noninvasive
      method for the management of bronchial asthma. In various cardiac diseases,
      bronchial hyperresponsiveness is observed, as is bronchial asthma. However, there
      have been few studies on the relationship between exhaled NO and bronchial
      responsiveness in cardiac diseases. OBJECTIVE: The aim of this study was to
      clarify the association between exhaled NO and bronchial hyperresponsiveness in
      patients with cardiac disease. METHODS: We measured expired NO and bronchial
      responsiveness to inhaled methacholine in 19 patients with cardiac diseases and
      17 with bronchial asthma. We divided the cardiac disease patients into two groups
      according to their bronchial responsiveness to inhaled methacholine: BHR(+) group
      consisted of 12 patients with bronchial hyperresponsiveness and BHR(-) group
      consisted of 7 patients without bronchial hyperresponsiveness. RESULTS: The
      concentration of exhaled NO in the asthmatic patients was significantly higher
      than that in the BHR(+) and BHR(-) groups (142.0 +/- 17.0, 33.6 +/- 6.4 and 42.3
      +/- 10.3 ppb, respectively, p < 0.01). There was no significant difference in
      exhaled NO between BHR(+) and BHR(-) groups. There were also no significant
      differences in the parameters of bronchial hyperresponsiveness between the
      cardiac BHR(+) and bronchial asthma groups. These results indicate that bronchial
      hyperresponsiveness in patients with cardiac diseases is not a consequence of
      eosinophilic inflammation or of exhaled NO. CONCLUSION: We conclude that
      bronchial hyperresponsiveness in patients with cardiac diseases can occur
      independently of NO production.

PMID- 11223728
TI  - Multiple logistic regression analysis of risk factors for the development of
      steroid-dependent asthma in the elderly: a comparison with younger asthmatics.
AB  - BACKGROUND: The percentage of the aged among all patients with bronchial asthma
      is increasing. OBJECTIVE: To investigate the risk factors for the development of
      steroid-dependent asthma in the elderly. METHODS: A multiple logistic regression
      analysis involving various clinical factors between steroid-dependent and 
      independent asthma was carried out for 59 asthmatics aged over 60 years,
      including 16 patients with steroid-dependent asthma. The calculated risk for each
      factor was compared with that obtained from 122 younger asthmatics aged 20-59
      years. RESULTS: Among the factors examined (sex, age, period from onset of
      asthma, type of asthma and family history of asthma, plus history of smoking,
      atopic dermatitis, allergic rhinitis, chronic sinusitis and nasal polyps), the
      significant risk factors for the development of steroid dependency in the elderly
      asthmatics were only family history of bronchial asthma (relative risk 3.6) and
      smoking history (relative risk 6.9). CONCLUSIONS: Some risk factors for steroid
      dependent asthma in younger individuals were not significant in the elderly.
      Since the smoking history was most closely associated with the development of
      steroid dependency in the elderly, even though most of them had quit smoking, it
      is important for patients with asthma to avoid smoking.

PMID- 11223730
TI  - Longitudinal changes of sensitization to farming-related antigens among young
      farmers.
AB  - BACKGROUND: We have shown previously that the prevalence of allergic
      sensitization in Tyrolean farming students is high, with a clear relationship to
      occupational exposure. OBJECTIVES: It was the aim of this investigation to assess
      longitudinal changes in sensitization and a possible impact on lung function.
      METHODS: Of the 147 farming students in the original cohort, we could re-examine
      42 after a mean interval of 4.0 years. All individuals completed a questionnaire
      and had spirometry, skin prick tests, total and specific IgE analysis, and
      testing for precipitating antibodies. RESULTS: As compared to the first study,
      there was a decrease in the frequency of IgE-mediated allergy (30.1 vs. 54.8%; p
      < 0.05) and in total serum IgE levels (107.4 +/- 254 vs. 157.8 +/- 304 U/ml; p <
      0.001). Conversely, 3 individuals had developed precipitating antibodies de novo,
      and those who had initially had a positive precipitin test (n = 6) were still
      positive. A larger-sized estate, the lack of a hay dryer, and the presence of
      moldy hay were confirmed as risk factors for allergic sensitization. Although
      there was a slight overall decrease in forced vital capacity, no new cases of
      occupational lung disease were found. CONCLUSIONS: In young Tyrolean dairy
      farmers, the prevalence of precipitins is constantly high and rising while IgE
      mediated allergy declines. Within 4 years, no clinically relevant impact of
      allergy on lung function was noticed.

PMID- 11223731
TI  - Dietary support to underweight patients with end-stage pulmonary disease assessed
      for lung transplantation.
AB  - BACKGROUND: Undernutrition in hospitalized patients is often not recognized and
      nutritional support neglected. Chronic obstructive pulmonary disease is
      frequently characterized by weight loss. No data exist on the effects of
      nutritional supplementation in underweight lung transplantation candidates during
      hospitalization. OBJECTIVE: To evaluate the effects on energy intake and body
      weight of an intensified nutritional support compared to the regular support
      during hospitalization. METHODS: The participants were underweight (n = 42) and
      normal-weight (n = 29) patients with end-stage pulmonary disease assessed for
      lung transplantation. The underweight patients were randomized to receive either
      an energy-rich diet planned for 10 MJ/day and 45-50 energy percentage fat and
      offered supplements (group 1), or the normal hospital diet planned for 8.5-9
      MJ/day and 30-35 energy percentage fat and regular support (group 2, control
      group). The normal-weight control patients (group 3) received the normal diet.
      Food intake was recorded for 3 days. RESULTS: During a mean hospital stay of 12
      days, the energy intake was significantly greater for the patients on intensified
      nutritional support (median 11.2 MJ) than for the underweight patients on the
      regular support (8.4 MJ; p < 0.02) and the normal-weight patients (7.0 MJ; p <
      0.001). The increase in energy intake in group 1 resulted in a significant weight
      gain (median 1.2 kg) compared with group 2 (p < 0.01) and group 3 (p < 0.001).
      CONCLUSIONS: In a group of underweight patients with lung disease assessed for
      lung transplantation, it was possible to increase energy intake by an intensified
      nutritional support which was associated with a significant weight gain, compared
      to the regular nutritional support during a short hospital stay.

PMID- 11223732
TI  - Initial bacterial colonization in patients admitted to a respiratory intensive
      care unit: bacteriological pattern and risk factors.
AB  - BACKGROUND: Colonization is an important risk factor for consecutive infection,
      but little is known about incidence and initial pattern on admission to
      respiratory intensive care units (RICU). OBJECTIVE: To study the bacterial
      colonization during the first 24 h after admission to a RICU. METHODS:
      Endotracheal aspirates, gastric juice, and pharyngeal and rectal swabs of 55
      consecutive patients were cultured (45 men, age 66 +/- 14 years, APACHE II 20.1
      +/- 5.6, no parenchymal infection). All samples were taken within the first 24 h
      after admission to a RICU. Potentially pathogenic microorganisms were grouped as
      community (c-PPM) and hospital acquired (h-PPM), and risk factors for
      colonization of each body site as well as for overall colonization (all sites
      excluding rectum) were identified by logistic regression analysis. RESULTS: The
      trachea was colonized in 18% of the intubated patients with c-PPMs and in 11%
      with h-PPMs. Candida spp. were the most frequent c-PPMs isolated from trachea,
      pharynx, and stomach (excluding rectal swabs), and Pseudomonas aeruginosa was the
      most frequently isolated h-PPM in trachea. The incidence of overall colonization
      was 49% for c-PPMs (predominantly Escherichia coli) and 18% for h-PPMs
      (predominantly P. aeruginosa). Admission to the hospital > or = 48 h before ICU
      admission was an independent risk factor of colonization with h-PPMs in
      univariate (33 vs. 7%, p = 0.015) and multivariate analyses (odds ratio 7.2, 95%
      CI 1.4-38.3; p = 0.0197). CONCLUSIONS: Colonization of the trachea with c-PPMs
      was already present in every 5th and with h-PPMs in every 10th intubated patient
      during the first 24 h of RICU admission even in the absence of parenchymal
      infections. Hospitalization more than 48 h prior to RICU admission was a risk
      factor of colonization with h-PPMs.

PMID- 11223733
TI  - Hospital charges attributable to bronchoscopy-related complications in
      outpatients.
AB  - BACKGROUND: Despite literature pertaining to algorithms of care, operating room
      charges and other financial management issues in medicine, there is a paucity of
      data pertaining to the fiscal consequences of bronchoscopic practice. OBJECTIVE:
      To identify hospital charges directly attributable to bronchoscopy-related
      complications in outpatients. METHODS: A prospective analysis of outpatient
      bronchoscopy-related complications, clinical outcomes and hospital charges
      resulting directly from procedure-related adverse events in 660 consecutive
      outpatients undergoing flexible fiberoptic bronchoscopy (FFB) during a period of
      30 consecutive months at the University of California, San Diego Medical Center,
      was performed. RESULTS: Altogether, 1,009 consecutive outpatient FFBs were
      performed on 660 patients (mean age 58 years, range 16-91 years). Fifty adverse
      events (5% of all procedures) occurred in 44 patients. These were bronchospasm
      (31 cases), hemoptysis (5 cases), pneumothorax (3 cases), nausea/vomiting (3
      cases), hypoxemia (2 cases), seizure (2 cases), laryngeal spasm (2 cases),
      chills/fever (1 case) and a vasovagal episode (1 case). Prolonged length of stay
      in the postprocedure recovery area on 22 occasions (2.2% of all procedures)
      resulted in USD 6,996 in additional hospital charges. Hospitalization was
      necessary in only 5 instances (0.5% of all procedures), but resulted in USD
      34,500 in additional charges (range for the 5 patients, USD 2,000-11,000) that
      were directly attributable to a procedure-related complication. CONCLUSION:
      Hospital charges directly attributable to outpatient flexible bronchoscopy
      related complications are minimal, but escalate considerably if hospitalization
      becomes necessary.

PMID- 11223734
TI  - Role of chemical mediators in airway hyperresponsiveness in an asthmatic model.
AB  - BACKGROUND: Airway hyperresponsiveness (AHR) is one of the characteristic
      features of human asthma. The presence of AHR and the precise mechanisms
      immediately after establishment of sensitization in guinea pigs are unclear,
      although there are many reports showing allergen exposure that causes an increase
      in bronchial responsiveness associated with eosinophil influx into the airway in
      sensitized guinea pigs. OBJECTIVE: We investigated the inhibitory effects on AHR
      to histamine of ONO-1078, a leukotriene antagonist; indomethacin, a
      cyclooxygenase inhibitor; S-145, a thromboxane A(2) (TXA(2)) antagonist, and Y
      24180, a platelet-activating factor (PAF) antagonist, to assess the involvement
      of chemical mediators in AHR employing ovalbumin (OA) sensitized guinea pig
      models. METHODS: Male Hartley guinea pigs were used. Each group comprised 4-7
      animals. The animals were sensitized to OA, injecting intraperitoneally 30 mg of
      cyclophosphamide and 2,000 microg of OA together with 100 mg of aluminum
      hydroxide as the adjuvant. The guinea pigs were artificially ventilated via a
      cannula using a small-animal respirator after intraperitoneal anesthesia with
      pentobarbital sodium for tracheotomy. The pressure at the airway opening (PAO)
      was measured using a differential pressure transducer, and a differential
      pressure of peak PAO (peak DeltaPAO) at inspiratory phase as an overall index of
      bronchial response to bronchoactive agents was used. While being artificially
      ventilated, the animals were exposed to physiological saline solution containing
      various concentrations of histamine (4.9, 9.8, 20, 39, 78, and 156 microg/ml) by
      inhalation for 30 s at 3-min intervals. Determinations were made at 1 min after
      each inhalation. The chemical mediators were each (30 mg/kg of ONO-1078, 3 mg/kg
      of S-1452, and 1 mg/kg of Y-24180) administered orally to sensitized guinea pigs,
      and the airway response to histamine was assessed. Each group comprised 4-7
      animals. RESULTS: The airway response to histamine was significantly greater in
      the sensitized group than in the nonsensitized group at histamine concentrations
      of 36 (p < 0.05), 78, and 156 mg/ml (p < 0.01). Leukotrienes C(4) and D(4): 30
      mg/kg of ONO-178 did not show any inhibitory effect on airway response to inhaled
      histamine. Cyclooxygenase: 5 mg/kg of indomethacin did not show any inhibitory
      effect on the airway response to inhaled histamine. TXA(2): the AHR to inhaled
      histamine at doses of 9.8, 39, 78, and 156 microg/ml was significantly inhibited
      by prior administration of 3 mg/kg of S-1452. PAF: the AHR to inhaled histamine
      at doses of 9.8, 39, and 78 microg/ml was significantly inhibited by prior
      administration of 1 mg/kg of Y-24180. CONCLUSIONS: S-1452 (3 mg/kg) and Y-24180
      (1 mg/kg) significantly inhibited AHR to histamine, while ONO-108 (30 mg/kg) and
      indomethacin (5 mg/kg) did not. The results suggest that TXA(2) and PAF are
      involved in AHR in OA-sensitized guinea pigs.

PMID- 11223735
TI  - Distal airspace enlargement in the fawn-hooded rat: influences of aging and
      alveolar wall destruction.
AB  - BACKGROUND: A recent study has revealed that the peripheral airspace in the lungs
      of the fawn-hooded rat (FHR) is enlarged. However, morphological and functional
      factors of the FHR lung have not been fully investigated. OBJECTIVE: The purpose
      of our study was to examine the structural and functional changes in the FHR lung
      and to investigate the influence of aging on this process. Furthermore,
      morphological and functional measurements of the lungs of FHRs (4-48 weeks of
      age) were performed and the results compared with those of age-matched Wistar
      control rats (WCRs). METHODS: All animals were studied under controlled
      conditions, and morphological and functional changes of the lungs were examined.
      Measurements of body and lung weights were recorded, and the lungs were subjected
      to morphological evaluation. Morphological measurements: mean linear intercept
      (MLI) and destructive index were determined. Functional evaluation of the lungs:
      total lung capacity, pressure-volume curve, and exponential constant (K) which
      describes the shape of the curve were analyzed. In addition, right ventricular
      hypertrophy measurements were performed to assess the severity of pulmonary
      hypertension. Statistical analysis was performed using the unpaired t test,
      analysis of variance, and the Fisher post hoc test (p < 0.05). RESULTS:
      Morphological analysis revealed a significant increase in airspace size (MLI) in
      all FHRs as compared with the WCRs which was evident from an early age (4 weeks).
      The increase in MLI did not progress age dependently in the FHR, whereas a
      tendency for an age-dependent increase in MLI was observed in the WCR. The
      destructive index measurements revealed that the increase in MLI of FHR was not
      accompanied by alveolar wall destruction. Concerning the functional examination,
      a leftward and upward shift of the pressure-volume curve was observed in the FHRs
      as compared with the WCRs at all ages. As compared with the WCRs, a higher K
      value was observed in all FHRs which was evident from an early age (4 weeks). Age
      dependent changes similar to those in MLI were observed in the K in both rat
      strains. CONCLUSIONS: The results of our study suggest that FHRs manifest
      characteristics of distal airspace enlargement accompanied by increased lung
      distensibility without alveolar wall destruction at an early age and that the
      changes do not progress age dependently. Neither an accelerated aging process nor
      destruction of the alveolar walls appears to be the mechanism responsible for the
      enlarged airspace in this rat strain.

PMID- 11223736
TI  - Chest wall tuberculosis.

PMID- 11223737
TI  - Bilateral empyema caused by adult-onset Still's disease.
AB  - Empyemas are usually of infectious origin. Noninfectious causes of empyema may be
      a considerable diagnostic challenge, as exemplified in the present case report. A
      21-year-old male presented with high fever, sore throat and myalgias of 1 week
      duration. In the following days, bilateral pleural effusions developed, with
      cellular counts in the pleural fluid up to 117 x 10(9)/liter (98% neutrophils).
      Despite institution of empiric antibiotic therapy, spiking fever continued. All
      culture studies resulted in being negative. Following the report of a serum
      ferritin concentration of 6,975 microg/l, adult-onset Still's disease was
      diagnosed and successfully treated with anti-inflammatory drugs. This case adds
      adult-onset Still's disease to the list of noninfectious causes of empyema and
      underlies the value of measuring serum ferritin as a diagnostic tool.

PMID- 11223738
TI  - Treatment of recurrent severe hemoptysis in cystic fibrosis with tranexamic acid.
AB  - Major hemoptysis is a potentially life-threatening complication of cystic
      fibrosis (CF) lung disease. Bronchial artery embolization (BAE) along with
      treatment of a CF pulmonary exacerbation has become the most widely used
      therapeutic approach for major hemoptysis in CF. However, BAE has been associated
      with severe complications, especially when bronchial artery to spinal artery
      anastomoses are present. This case study describes the successful treatment of
      major hemoptysis in CF with tranexamic acid, in an individual in whom 12 previous
      BAE procedures had been performed and further procedures were contraindicated
      secondary to bronchial artery to spinal artery collaterals. Recurrence of the
      hemoptysis occurred after attempts had been made to withdraw the tranexamic acid.
      Tranexamic acid was resumed with resolution of the hemoptysis, and the therapy
      has been used continuously for 13 months without any complications.

PMID- 11223739
TI  - A rare case of bronchial glomus tumor.
AB  - A 48-year-old man was admitted because of bloody sputum in whom a chest computed
      tomography (CT) scan and fiberoptic bronchoscopy demonstrated a polypoid tumor in
      the left main bronchus. The tumor was surgically resected, and the pathological
      and immunohistochemical findings led to diagnosis of the tumor as a bronchial
      glomus tumor.

PMID- 11223740
TI  - Primary endobronchial leiomyosarcoma. Diagnosis following expectoration of tumor
      fragment.
AB  - A case is presented with spontaneous expectoration of a small piece of solid
      tissue. Pathologic examination of the expectorated tissue was found to be
      consistent with leiomyosarcoma. After further work-up, there was no evidence of
      another primary site of leiomyosarcoma except for the right lower lobe. Right
      lower lobectomy was performed. The surgical specimen showed a tumor that was
      histologically identical to the patient's previous expectorated tissue. To the
      authors' knowledge, this is the first report of partial expectoration of a
      primary endobronchial leiomyosarcoma.

PMID- 11223741
TI  - Airway foreign body with clinical features mimicking bronchial asthma.
AB  - A 56-year-old Japanese male with persistent cough, stridor and diffuse wheezing
      for 6 months had obstructive pulmonary dysfunction and airway hyperresponsiveness
      (AHR) to inhaled methacholine. Because of a poor response to glucocorticoid
      therapy and neutrophilia in the peripheral blood and sputum, chest computed
      tomography was performed and a plate-like tumor in the truncus intermedius was
      identified. Fiberoptic bronchoscopy demonstrated a plate-like green-colored tumor
      firmly impacted into the truncus intermedius and diffuse inflammatory changes
      spreading to both main bronchi. A piece of 'kombu' (Japanese kelp) was
      successfully removed by fiberoptic bronchoscopy under general anesthesia.
      Pulmonary function and methacholine inhalation tests became normal after the
      removal of the foreign body. In this case, it is suggested that asthma-like
      symptoms were due to localized airflow limitation in the right bronchus as well
      as to AHR associated with diffuse airway neutrophilic inflammation.

PMID- 11223742
TI  - Radicular involvement and medullary invasion from a malignant mesothelioma.
AB  - We present the case of a 57-year-old patient who had worked at a fiber-cement
      factory for 28 years. The patient developed an epithelioid-type pleural
      mesothelioma 5 years after retiring, after he was diagnosed with asbestosis. Only
      5 months after the diagnosis of mesothelioma, a medullar section appeared to be
      totally invaded by a tumor in the medullar canal, thus causing paraplegia and
      affecting the bladder and anal sphincters. The patient underwent radiotherapy and
      chemotherapy, and achieved partial recovery, but died 9 months after the
      diagnosis.

PMID- 11223743
TI  - Pulmonary mucosa-associated lymphoid tissue lymphoma in a patient with common
      variable immunodeficiency syndrome.
AB  - Common variable immunodeficiency syndrome (CVID) is a primary immunodeficiency
      typically presenting with recurrent sinopulmonary infections. Non-Hodgkin's
      lymphoma and other secondary cancers are typical late complications of CVID. We
      report on a patient suffering from CVID with a history of recurrent sinopulmonary
      infections, interstitial pulmonary changes and hepatic granulomas. Despite
      treatment with intravenous immunoglobulin followed by a reduction in the number
      of pulmonary infections, reticular and nodular lung changes progressed. Video
      assisted thoracoscopic lung biopsy showed a low-grade B cell lymphoma of the
      mucosa-associated lymphoid tissue (MALT) of the bronchus without evidence of
      pulmonary infection. In conclusion, MALT lymphoma of the lung should be
      considered in the differential diagnosis of progressive lung disease in CVID.

PMID- 11223744
TI  - Acute dyspnea after delivery.

PMID- 11223745
TI  - Extracorporeal shock wave lithotripsy in ureteral and kidney malformations.
AB  - INTRODUCTION: Extracorporeal shock wave lithotripsy (SWL) has long been accepted
      worldwide in the treatment of kidney stone disease. Upper ureter calculi in
      ureteral and kidney malformations are rather frequent (10-25%). The aims of this
      retrospective study were to determine whether malformations might impair fragment
      expulsion. MATERIAL AND METHODS: From 1986 to 1995, 203 patients with ureteral
      and kidney malformations were treated and followed up for a minimum of 1 year to
      a maximum of 9 years. Malformations included: ureteropelvic junction stenosis,
      horseshoe kidney, renal malrotation, renal ectopia, duplicated ureter,
      nonobstructive megaureter, medullary sponge kidney and caliceal diverticula. As
      pretreatment workup, all patients underwent conventional studies prior to SWL
      treatment: X-rays, renal ultrasound, intravenous pyelography, routine blood tests
      and urinalysis. All examinations were repeated at regular intervals for the first
      6 months. Patients with metabolic disorders were excluded from the study. We also
      excluded patients with a follow-up of under 1 year. We considered three groups of
      patients: (1) stone-free patients at plain X-rays and ultrasound; (2) >90%
      elimination, i.e. stone-free patients at plain X-rays and positive at ultrasound;
      (3) patients with residual fragments at plain X-rays and ultrasound. RESULTS: 96
      (55%) patients were in group 1 (stone free), 40 (19%) were in group 2 (>90%
      elimination) and 67 (26%) were in group 3 (residual). Residual stones were more
      frequent in patients with medullary sponge kidney (82%). In patients with renal
      ectopia the residual stone rate accounted for only 13% of cases. CONCLUSIONS:
      There is evidence that SWL should always be offered to patients with ureteral and
      kidney malformations. These patients should however be considered at high risk
      for recurrences and so they need to be carefully followed up.

PMID- 11223746
TI  - Comparison of ultrasound-guided biopsies and prostatectomy specimens: predictive
      accuracy of Gleason score and tumor site.
AB  - OBJECTIVE: To critically evaluate the accuracy of sextant biopsies in predicting
      Gleason score and the site of tumor location in patients with clinically
      localized prostate cancer treated by radical perineal prostatectomy. METHODS: The
      case records of 289 patients with clinically localized prostate cancer who
      underwent radical perineal prostatectomy were reviewed, comparing the Gleason
      score and tumor site location as determined by sextant ultrasound-guided core
      biopsies with the Gleason score and tumor distribution within the surgical
      specimens. The prostatectomy specimens were further characterized by extent of
      disease as organ-confined, specimen-confined or margin-positive. RESULTS: The
      Gleason score was identical in 126 (43.5%) patients. An upgrading in the surgical
      specimen occurred in 118 (40.8%) cases, a downgrading in 43 (14.8%). Overall, 193
      (66.7%) patients had a unilateral positive biopsy, while 96 (33.2%) patients had
      bilateral positive biopsies. Sixty-four (33.1%) patients with a unilateral
      positive biopsy had cancer confined to one side of the gland, while 127 (65.8%)
      showed bilateral disease; 142 (73.5%) patients had organ-confined tumors versus
      51 (26.4%) patients with capsular penetration. In the 96 patients with bilateral
      positive biopsies, 64 (66.6%) patients had intracapsular cancer versus 32 (33.3%)
      patients with either specimen-confined or margin-positive disease. The overall
      rate of positive margins was 14%. Fifty-one (61.4%) of the 83 patients with non
      organ-confined disease had posterolateral capsular penetration in the region of
      the superior pedicle of the neurovascular bundle, while 28 (33.7%) patients had
      apical capsular penetration, in the region of the inferior neurovascular pedicle.
      CONCLUSIONS: The ability of sextant ultrasound-guided biopsies to estimate the
      pathological grading is satisfactory: when we consider a difference of +/- 1 in
      the final Gleason score, the overall correlation is 80%. In 66% of the cases,
      sextant biopsies predicted unilateral disease when bilateral disease existed. A
      unilateral positive biopsy does not predict unilateral disease.

PMID- 11223748
TI  - P53 mutations and other prognostic factors of renal cell carcinoma.
AB  - OBJECTIVE: Tumor stage, histological pattern, cell type, diameter and cell ploidy
      are the factor that have been proposed for predicting the prognosis of renal cell
      carcinoma (RCC). There is a wide variation in the reported incidence of p53
      mutation in RCC, and its prognostic significance for this tumor is unknown. We
      investigated the prognostic value of p53 mutations among other prognostic
      factors. PATIENTS AND METHOD: We evaluated the stages, tumor diameters,
      histological grades, cellular patterns and the presence of mutant p53 protein in
      50 cases of RCC. The survival function of each parameter was estimated by Kaplan
      Meier and log-rank tests, and the significance of each parameter on survival was
      evaluated by logistic regression analysis. RESULTS: The p53 mutation incidence
      was 20% in the RCC cases included in the study (n = 50). The survival rates of
      stages pT(2), pT(3) and pT(2-3)N+ were 87.8, 61.0 and 0%, respectively (p =
      0.0462). The survival analysis of grade 1-2 and grade 3-4 tumors revealed 92.3
      and 51.5% survival rates, respectively (p = 0.002). The survival rates of mutant
      p53+ and mutant p53- cases were 33.3 and 84.2%, respectively (p = 0.0027). The
      logistic regression test analysis demonstrated that tumor grade, tumor stage and
      mutant p53 positivity status were the most significant prognostic factors (p <
      0.03). The survival rates of mutant p53+ and p53- cases at stages pT(2), pT(3)
      and pT(2-3)N+ were 66.67 versus 91.48%, 33.3 versus 71.43% and 0 versus 100%,
      respectively (p = 0.0392). A similar finding was present at each stage for
      cellular grades (p = 0.0093). The survival rates of mutant p53+ and p53- cases
      for grades 3 and 4 were 33.33 and 74.48%, respectively (p = 0.2731). CONCLUSION:
      Our results suggested that many parameters can affect survival of RCC cases, but
      among these, tumor grade, tumor stage and p53 mutation status are the most
      important prognostic factors, but p53 mutation status and cellular grade can
      afford additional prognostic information at each stage.

PMID- 11223747
TI  - Comparison of cytology and nuclear matrix protein 22 for the detection and follow
      up of bladder cancer.
AB  - OBJECTIVES: This study was designed to determine the clinical usefulness of the
      nuclear matrix METHODS: 84 patients suffering from bladder cancer or suspected
      bladder cancer, 25 patients with benign urological lesions and 60 healthy
      controls participated in a prospective study. Freshly voided spot urine samples
      were taken for cytological examination and determination of NMP 22 levels by
      enzyme-linked immunoassay. RESULTS: The sensitivity of the NMP 22 test according
      to the tumor grading was (results of cytology in brackets): G1 25.0% (20.0%); G2
      68.2% (59.1%), and G3 100.0% (66.7); overall sensitivity was 62.5% (45.0%). The
      sensitivity for superficial bladder cancer was 46.7% (36.7%) and for invasive
      bladder cancer 90.0% (70.0%). The specificity was 65.9% (88.9%). CONCLUSIONS: NMP
      22 is a reliable tool for detecting invasive bladder cancer. Results for the
      frequently occurring low grade superficial bladder cancer are as poor as those
      obtained with cytology. In addition benign lesions such as urolithiasis or
      urinary tract infection lead to false-positive results. Therefore cystoscopy has
      to be performed when trying to detect and follow-up bladder cancer.

PMID- 11223749
TI  - Discontinuation of alpha-blockade after initial treatment with finasteride and
      doxazosin for bladder outlet obstruction.
AB  - OBJECTIVES: Patients with symptomatic bladder outlet obstruction and moderately
      enlarged prostates can receive durable relief from finasteride. However, the
      delayed onset of action has led many clinicians to prescribe an alpha-blocker in
      addition to finasteride early in therapy for more rapid symptom relief. Our goal
      was to determine when to discontinue the alpha-blocker in this group of patients.
      METHODS: We enrolled 100 consecutive men with an estimated prostate size of >40 g
      and an AUA symptom score of > or =20, who reported an initially favorable
      response to combination therapy with 5 mg finasteride and 2 mg doxazosin daily.
      The average symptom score reduction at 1 month was 3.3. We discontinued the
      doxazosin at 3, 6, 9, or 12 months, while continuing finasteride, then
      reevaluated patients 1 month later to determine if the patients reported any
      worsening of symptoms. RESULTS: Twenty-five patients discontinued doxazosin at 3
      months. Five (20%) were successfully discontinued, reporting no change in symptom
      score. Twenty reported worsening symptoms. Twenty-five patients discontinued
      doxazosin at 6 months. Twelve (48%) were successfully discontinued, reporting no
      change in symptom scores. Thirteen (52%) reported worsening symptoms. Twenty-five
      patients discontinued doxazosin at 9 months. Twenty-one (84%) were successfully
      discontinued, reporting no change in symptom scores. Four (16%) reported
      worsening symptoms. Twenty-five patients discontinued doxazosin at 12 months.
      Twenty-one (84%) were successfully discontinued, reporting no change in symptom
      scores. Four (16%) reported worsening symptoms. CONCLUSION: Patients with
      symptomatic bladder outlet obstruction and moderately enlarged prostates who are
      placed initially on combination therapy using finasteride and an alpha-blocker
      are likely to tolerate discontinuation of the alpha-blocker after 9 months of
      combination therapy.

PMID- 11223750
TI  - Pressure-flow studies in men with benign prostatic hypertrophy before and after
      treatment with transurethral needle ablation.
AB  - BACKGROUND/AIMS: In this study we wanted to examine the effects that
      transurethral needle ablation (TUNA) might have on the urodynamic characteristics
      of bladder outlet obstruction and to evaluate the clinical changes and the safety
      profile in patients undergoing the TUNA procedure, including the effects on
      erectile and ejaculatory function. MATERIALS AND METHODS: We evaluated 24
      patients, aged between 66 and 81 (mean 73.4) years with a mean prostatic volume
      of 57 +/- 15 ml. Before treatment, the clinical history was collected, then
      prostate-specific antigen (PSA) analysis, digital rectal examinations, I-PSS and
      quality-of-life (QOL) tests, uroflowmetry with residual volume, and pressure-flow
      studies were performed in all patients. After treatment, all the patients were
      evaluated at 6, 12 and 24 months by the same parameters. RESULTS: After
      treatment, the I-PSS and QOL scores were considerably improved, and the mean flow
      rate and the residual volume were also improved. The serum PSA level remained
      unchanged. The prostatic volume was almost unchanged, and pressure-flow studies
      showed a reduction in the mean opening pressure and detrusor pressure at maximum
      flow after treatment. None of the patients complained of alterations in sexual
      activity nor retrograde ejaculation. CONCLUSIONS: Our study confirms that in
      patients with benign prostatic hyperplasia, the TUNA procedure results in no
      major complications and in significant clinical improvements. There was an
      improvement in the subjective and objective variables, such as symptom scores and
      frequency-volume charts and, in the majority of patients, subjective and
      objective improvements were sustained for the duration of this study, which
      included a 2-year follow-up with pressure-flow studies. From our experience we
      can say that the ideal candidate for TUNA treatment should be younger than 70
      years, with a prostatic volume of <60 cm H(2)O, with a baseline detrusor pressure
      at maximum flow of <60 cm H(2)O, with a pretreatment residual volume of <100 ml
      and with a QOL score of <5.

PMID- 11223751
TI  - Unilateral testicular torsion: evaluation of bcl-2, p-53 and PCNA expression in
      contralateral testes.
AB  - OBJECTIVES AND METHODS: The present study aims to evaluate the histologic as well
      as apoptotic changes indicated by PCNA, p-53 and bcl-2 expression in the
      contralateral testes after a period of unilateral testicular torsion of 4 h.
      RESULTS: Regarding the histologic changes, while some significant alterations
      such as complete or incomplete spermatocytic arrest as well as sertoli cell only
      formation have to some extent been noted after the detorsion procedure,
      reasonably better preserved histology could be demonstrated following the
      orchiectomy procedure both in the early and late follow-up. Thus, the orchiectomy
      procedure was found to be limiting enough on the severity of the histologic
      changes in the contralateral testes after a certain period of time following the
      torsion procedure. On the other hand, however, in relation to the apoptotic
      events indicated by the three markers, while PCNA activity was found to be
      significantly different depending on the procedure performed (detorsion or
      orchiectomy), p-53 and bcl-2 positivity did not exhibit any difference in this
      aspect. Increased PCNA activity (especially after the detorsion procedure)
      together with marked positivity of p-53 both in the early and late follow-up
      indicated the increased cell turnover in the contralateral testes, which in turn
      may be accepted as a sign of increased apoptosis in these testes. In addition to
      these findings, bcl-2 expression has been found to be consistently negative in
      all specimens evaluated both in the early and late follow-up. CONCLUSION: Taking
      into account the strong inhibitory effect of bcl-2 during apoptotic events, these
      findings again support the likelihood of increased apoptosis in the contralateral
      testes.

PMID- 11223752
TI  - Regional variations in thiol distribution pattern and superoxide dismutase
      activity of the male reproductive tract of the rat modulate the transport of
      spermatozoa through the epididymis and vas deferens.
AB  - BACKGROUND: Contractile activity of the muscular coat of the epididymis wall is
      considered the major driving force for the propulsion of sperm through the male
      reproductive tract. METHODS: Region-specific changes in the status of membrane
      thiols and the free radical scavening potential of the male reproductive tract of
      the rat were observed. RESULTS: The present study shows that the local
      biochemical milieu has some influence on the transport of spermatozoa through the
      male reproductive tract. The vas deferens showed a higher level of superoxide
      dismutase activity and a low profile of thiol exposure. CONCLUSION: We conclude
      that the strong scavenging potential and the lesser thiol exposure of the vas
      create an apparently inert vas lumen which facilitates the transit of spermatozoa
      through the vas.

PMID- 11223753
TI  - Five-year prognosis after radical prostatectomy in a patient with localized
      prostate cancer and incidental non-Hodgkin's lymphoma.
AB  - We present a white male patient with an initial prostate-specific antigen level
      of 69 ng/ml, referred for urological evaluation. He was found to be free of
      prostatitis but diagnosed for prostate adenocarcinoma without any indications of
      metastatic disease. Lymphadenectomy then revealed lymphadenopathy of low-grade
      non-Hodgkin's lymphoma. Five-year follow-up after radical retropubic
      prostatectomy (RRP) showed no evidence of metastatic or local prostate cancer
      recurrence. In addition, no radiation or chemotherapy was required for his
      lymphoma. Although RRP is a viable option in this unique case, the outcome thus
      far suggests that it should be considered a primary therapeutic modality.

PMID- 11223754
TI  - Paraganglioma and adrenal pheochromocytoma presenting simultaneously in an
      elderly female. Case report and review of the literature.
AB  - Paragangliomas are chromaffin tissue tumors arising in an extra-adrenal location.
      It is quite rare to find a paraganglioma concurrently with a pheochromocytoma. We
      report a patient who underwent resection of a retroperitoneal mass that was
      characterized pathologically as a malignant paraganglioma. An incidental finding
      was a microscopic pheochromocytoma in the ipsilateral adrenal gland.

PMID- 11223755
TI  - Missed stab wound of the ureter treated by antegrade stenting alone.
AB  - Ureteric injury complicates 1% of penetrating abdominal trauma. Detection and
      management of this rare complication is difficult. We present the case of a 32
      year-old man who presented with a penetrating ureteric trauma that was treated by
      antegrade stenting.

PMID- 11223756
TI  - Idiopathic calcification of the seminal vesicles: a rare cause for prostate
      cancer overstaging.
AB  - Calcification of the seminal vesicles is a rare phenomenon. We present 2 cases in
      whom calcification of the seminal vesicles led to preoperative overstaging of
      prostate cancer. Although idiopathic calcifications are extremely rare,
      calcifications appear more frequently in diabetic patients. Therefore, knowledge
      of these formations is essential to prevent overstaging, namely infiltration of
      the seminal vesicles.

PMID- 11223757
TI  - Malignant priapism associated with metastatic urethral carcinoma.
AB  - We present a 40-year-old man with malignant priapism secondary to urethral
      squamous cell carcinoma. Magnetic resonance imaging revealed the tumor
      originating from the bulbous urethra, extending into the penile urethra and
      corpora spongiosa and cavernosa. A penile biopsy confirmed poorly differentiated
      squamous cell carcinoma of the urethra. Despite administration of systemic
      chemotherapy, the prognosis of the patient has worsened due to the extensive
      metastatic disease.

PMID- 11223758
TI  - Concealed penis: rare complication of circumcision.
AB  - A man presented with a concealed penis which developed after circumcision. In
      addition to anatomic variations in penile skin attachment and obesity,
      circumcision is an iatrogenic cause in the etiology of a concealed penis.
      Although it is a frequent and simple operation, it may lead to uncommon
      complications due to a lack of experience and poor technique.

PMID- 11223759
TI  - Spontaneous regression of hepatic metastases after nephrectomy and metastasectomy
      of renal cell carcinoma.
AB  - We report a case of clear cell carcinoma of the kidney with multifocal metastases
      to the lymph nodes, vagina and liver. Spontaneous regression of liver metastasis
      has been described after nephrectomy. Surgical management of primary and
      metastatic tumors should be considered in all patients with renal cell carcinoma.

PMID- 11223760
TI  - Outpatient treatment of deep venous thrombosis: a clinical care pathway managed
      by the emergency department.
AB  - STUDY OBJECTIVE: We evaluate the effectiveness and safety of an outpatient
      clinical care pathway for the initial treatment of acute proximal lower-extremity
      deep venous thrombosis (DVT) with low molecular weight heparin (LMWH) managed by
      the emergency department of 2 affiliated community hospitals. METHODS: This
      observational, retrospectively defined, population-based study with 39(1/2)
      months of preintervention analysis and 32(1/2) months of postintervention
      analysis was conducted in 2 suburban EDs of a large group model health
      maintenance organization. Our outpatient DVT clinical care pathway used careful
      patient selection and multidisciplinary follow-up. Ninety-six patients before the
      intervention and 178 patients after the intervention met eligibility criteria for
      the pathway. Adverse events during the first 2 weeks of treatment included
      symptomatic pulmonary embolism (PE), progressive DVT, minor and major bleeding,
      and death. RESULTS: Demographic and baseline clinical characteristics of the 2
      groups were similar. Five (5.2%) of 96 preintervention subjects (95% confidence
      interval [CI] 2.4 to 8.1) developed adverse events compared with 5 (2.8%) of 178
      postintervention subjects (95% CI 1.5 to 4.1; difference between groups 2.4%; P
      =.50). In each group, 1 (1.0% versus 0.6%) subject developed a PE, 2 (2.1% versus
      1.1%) developed progressive symptoms of progressive DVT, and 2 (2.1% versus 1.1%)
      developed minor bleeding. Major bleeding occurred in 1 (1.0%) preintervention
      subject and no postintervention subjects. No patient in either cohort died.
      CONCLUSION: Managed by the ED, an outpatient DVT clinical care pathway using
      careful patient selection and an integrated multidisciplinary approach can
      provide a similar degree of effectiveness and safety as customary inpatient
      therapy.

PMID- 11223761
TI  - Awareness and use of the Ottawa ankle and knee rules in 5 countries: can
      publication alone be enough to change practice?
AB  - STUDY OBJECTIVES: We evaluate the international diffusion of the Ottawa Ankle and
      Knee Rules and determine emergency physicians' attitudes toward clinical decision
      rules in general. METHODS: We conducted a cross-sectional, self-administered mail
      survey of random samples of 500 members each of the American College of Emergency
      Physicians, Canadian Association of Emergency Physicians, British Association for
      Accident and Emergency Medicine, Spanish Society for Emergency Medicine, and all
      members (n=1,350) of the French Speaking Society of Emergency Physicians, France.
      Main outcome measures were awareness of the Ottawa Ankle and Knee Rules, reported
      use of these rules, and attitudes toward clinical decision rules in general.
      RESULTS: A total of 1,769 (57%) emergency physicians responded, with country
      specific response rates between 49% (United States and France) and 79% (Canada).
      More than 69% of physicians in all countries, except Spain, were aware of the
      Ottawa Ankle Rules. Use of the Ottawa Ankle Rules differed by country with more
      than 70% of all responding Canadian and United Kingdom physicians reporting
      frequent use of the rules compared with fewer than one third of US, French, and
      Spanish physicians. The Ottawa Knee Rule was less well known and less used by
      physicians in all countries. Most physicians in all countries viewed decision
      rules as intended to improve the quality of health care (>78%), a convenient
      source of advice (>67%), and good educational tools (>61%). Of all physicians,
      those from the United States held the least positive attitudes toward decision
      rules. CONCLUSION: This constitutes the largest international survey of emergency
      physicians' attitudes toward and use of clinical decision rules. Striking
      differences were apparent among countries with regard to knowledge and use of
      decision rules. Despite similar awareness in the United States, Canada, and the
      United Kingdom, US physicians appeared much less likely to use the Ottawa Ankle
      Rules. Future research should investigate factors leading to differences in rates
      of diffusion among countries and address strategies to enhance dissemination and
      implementation of such rules in the emergency department.

PMID- 11223762
TI  - Maximizing use of the emergency department observation unit: a novel hybrid
      design.
AB  - STUDY OBJECTIVE: We sought to determine whether sharing an observation unit with
      scheduled procedure patients would maintain a more consistent unit census and
      patient/nurse ratio. A secondary objective was to determine the effect of this
      model on patient length of stay and discharge rates. METHODS: This retrospective,
      descriptive study was conducted in a high-volume suburban teaching hospital,
      using a "before-and-after" study design. A "pure" postprocedure unit became a
      "hybrid" observation postprocedure unit by displacing specific postprocedure
      patients to inpatient locations. Subsequently, the displaced patients were
      returned to the unit. On weekends, the unit operated as a pure observation unit.
      Hourly unit occupancy and census data were prospectively collected, and hourly
      patient/nurse ratios were calculated. Patient length of stay and discharge data
      were collected and compared in different settings. RESULTS: The 2 services showed
      a complementary census pattern that allowed the hybrid unit to maintain an
      average hourly patient/nurse ratio of 3.7 compared with the ratio of 2.5 for a
      pure observation unit. There was no difference in observation patient length of
      stay (14.8 hours versus 14.7 hours) or discharge rate (20.4% versus 18.1%)
      between weekdays and weekends. However, scheduled procedure patients experienced
      significantly shorter lengths of stay in the hybrid unit setting (4.3 hours) than
      in alternative inpatient locations (9.4 hours). CONCLUSION: The hybrid model
      showed better hourly census and nurse resource use rates, with no adverse effect
      on observation patients. However, scheduled procedure patient length of stay was
      shorter in this setting.

PMID- 11223763
TI  - Medical student effect on emergency department length of stay.
AB  - STUDY OBJECTIVE: Taking advantage of a medical student strike, the authors
      evaluated the effect of medical students on emergency department length of stay
      (LOS). METHODS: ED LOS and patient characteristics were compared for the 4-day
      strike period and the same days the week before. Proportions were compared by
      using the Mann-Whitney U test and the chi(2) test (P <.05). RESULTS: Eight
      hundred thirty-one patients were studied. There was no significant difference
      between the study and control periods for the general patient characteristics or
      laboratory or radiologic investigations. Median LOS decreased by 24% (31 minutes,
      95% confidence interval [CI] 24 to 38) during the strike (110 minutes [95% CI 65
      to 178] to 79 minutes [95% CI 40 to 135], P <10(-4)). CONCLUSION: Medical
      students lengthen ED LOS. This should be explained to patients and should be
      considered as one justification for increasing medical staff in the teaching ED.

PMID- 11223764
TI  - Wilderness mortalities: a 13-year experience.
AB  - STUDY OBJECTIVE: To analyze the epidemiology of wilderness mortalities in a
      localized area with diverse terrain. METHODS: We conducted a retrospective review
      of the Pima County (Arizona) Sheriff's Office (PCSO) search and rescue logs and
      case reports, hospital records, and autopsy reports for all wilderness deaths
      from 1980 to 1992. The study group comprised all victims of injury or illness in
      Pima County wilderness who died during a 13-year period in a location remote
      enough so that standard ground-based emergency medical services units could not
      extract the body. RESULTS: One hundred fatalities occurred during the 13-year
      study period. There were 59 unintentional traumas, 18 suicides, 9 homicides, 12
      medically related deaths, and 2 deaths of unknown causes. Toxicology tests
      performed on body fluids yielded positive findings for alcohol in a total of 50
      (50%) cases and positive findings for drugs of abuse in 12 (12%) cases. It was
      estimated that alcohol was "a very probable" or "a probable" causative factor in
      23 (40%) of the 59 unintentional trauma deaths, and in 1 (8.3%) of the 12
      medically related deaths. Fifty-five (55%) deaths were witnessed events, with 45
      (80%) of these victims reported as dying immediately or before arrival of search
      and rescue personnel. Ten (10%) victims received resuscitation in the field, and
      according to a review of hospital charts and autopsy reports, only 2 victims had
      a potentially survivable injury or illness. CONCLUSION: Many wilderness
      mortalities are related to incidents involving alcohol. Once the accident or
      injury has occurred, the majority of deaths are immediate, or at least before the
      arrival of medical personnel. Higher levels of medical care would not have
      improved the outcomes of those who did survive long enough to receive medical
      care. Therefore, primary efforts to reduce mortalities in the wilderness should
      be directed toward prevention, especially diminishing alcohol use in wilderness
      areas.

PMID- 11223765
TI  - Better health while you wait: a controlled trial of a computer-based intervention
      for screening and health promotion in the emergency department.
AB  - STUDY OBJECTIVE: We evaluate a computer-based intervention for screening and
      health promotion in the emergency department and determine its effect on patient
      recall of health advice. METHODS: This controlled clinical trial, with
      alternating assignment of patients to a computer intervention (prevention group)
      or usual care, was conducted in a university hospital ED. The study group
      consisted of 542 adult patients with nonurgent conditions. The study intervention
      was a self-administered computer survey generating individualized health
      information. Outcome measures were (1) patient willingness to take a computerized
      health risk assessment, (2) disclosure of behavioral risk factors, (3) requests
      for health information, and (4) remembered health advice. RESULTS: Eighty-nine
      percent (470/542) of eligible patients participated. Ninety percent were black.
      Eighty-five percent (210/248) of patients in the prevention group disclosed 1 or
      more major behavioral risk factors including current smoking (79/248; 32%),
      untreated hypertension (28/248; 13%), problem drinking (46/248; 19%), use of
      street drugs (33/248; 13%), major depression (87/248; 35%), unsafe sexual
      behavior (84/248; 33%), and several other injury-prone behaviors. Ninety-five
      percent of patients in the prevention group requested health information. On
      follow-up at 1 week, 62% (133/216) of the prevention group patients compared with
      27% (48/180) of the control subjects remembered receiving advice on what they
      could do to improve their health (relative risk 2.3, 95% confidence interval 1.77
      to 3.01). CONCLUSION: Using a self-administered computer-based health risk
      assessment, the majority of patients in our urban ED disclosed important health
      risks and requested information. They were more likely than a control group to
      remember receiving advice on what they could do to improve their health. Computer
      methodology may enable physicians to use patient waiting time for health
      promotion and to target at-risk patients for specific interventions.

PMID- 11223766
TI  - Violent injuries among adolescents: declining morbidity and mortality in an urban
      population.
AB  - STUDY OBJECTIVE: Adolescent homicide rates are decreasing nationally for unclear
      reasons. We explore changes in intentional injury morbidity and mortality within
      the context of other injuries and specific causes. METHODS: We performed
      surveillance of hospital, medical examiner, and vital records for nonfatal injury
      among adolescents age 10 to 19 years living in the District of Columbia from June
      15, 1996, to June 15, 1998, and fatal injury from 1989 to 1998. RESULTS: Over the
      2-year study period, 15,190 adolescents were seen for injury, resulting in an
      event-based rate of 148 injuries per 1,000 adolescents per year; 7% required
      hospitalization, and 0.8% died. Interpersonal intentional injuries accounted for
      25% of all injuries, 45% of hospitalizations, and 85% of injury deaths. Assault
      morbidity decreased with no change noted for unintentional and self-inflicted
      injury. Firearm injuries, stabs, and assaults with other objects showed the
      largest decrease, with no decrease in unarmed assaults. Injury mortality peaked
      in 1993 and has declined since. Firearms caused 72% to 90% of all injury deaths
      from 1989 to 1998, most the result of homicide. CONCLUSION: There has been a
      decline in intentional injury rates over the study periods related to decreased
      weapon injury; data suggest a change in the lethality of fighting methods but no
      change in unarmed fighting behavior.

PMID- 11223767
TI  - Emergency visits for sports-related injuries.
AB  - STUDY OBJECTIVE: We sought to estimate the effect and magnitude of patients with
      sports-related injuries presenting to hospital emergency departments in the
      United States and to examine differences in patient and visit characteristics
      between sports- and nonsports-related injuries. METHODS: Data from the 1997 and
      1998 National Hospital Ambulatory Medical Care Survey, a national probabilistic
      sample of 496 US hospital EDs, were combined to examine emergency visits for
      sports-related injuries. Data from 16,997 sample ED encounter records for
      injuries that included narrative cause of injury text were analyzed. Narrative
      text entries were coded to 1 of 84 sport and recreational activity codes. Sample
      weights were applied to provide annual national estimates. Estimates of sports
      related injury visits were based on 1,775 records with an assigned sports-related
      activity code. RESULTS: There were an average annual estimated 2.6 million
      emergency visits for sports-related injuries by persons between the ages of 5 and
      24 years. They accounted for over 68% of the total 3.7 million sport injuries
      presented to the ED by persons of all ages. As a proportion of all kinds of
      injuries presenting to the ED, sports-related injuries accounted for more than
      one fifth of the visits by persons 5 to 24 years old. The use rate was 33.9 ED
      visits per 1,000 persons in this age group (95% confidence interval 30.3 to
      37.5). The sports-related injury visit rate for male patients was more than
      double the rate for female patients (48.2 versus 19.2 per 1,000 persons between 5
      and 24 years of age). Visits from sports-related activities for this age group
      were more frequent for basketball and cycling compared with other categories (eg,
      baseball, skateboarding, gymnastics). Compared with nonsports-related injuries
      for this age group, sports-related injuries were more likely to be to the brain
      or skull and upper and lower extremities. Patients with sports-related injuries
      were more likely to have a diagnosis of fracture and sprain or strain and less
      likely to have an open wound. They were also more likely to have diagnostic and
      therapeutic services provided, especially orthopedic care. CONCLUSION: Sports
      related activities by school-age children and young adults produce a significant
      amount of emergency medical use in the United States. The ED is an appropriate
      venue to target injury prevention counseling.

PMID- 11223768
TI  - Paying for hospital emergency care under a single-payer system.
AB  - Hospital emergency services are one of the key drivers of hospital activity, yet
      there has been surprisingly little attention paid to appropriate funding models
      for single-payer systems, in which funders must be concerned with issues of
      access and financial viability of emergency departments. This article analyzes
      the dynamics of hospital emergency services in terms of the key products and cost
      drivers. It reviews the currently available systems for categorizing emergency
      activity and evaluates their applicability for funding purposes with particular
      emphasis on the susceptibility to gaming of both triage and disposition. It
      identifies and evaluates 3 models for use in single-payer health systems for
      funding hospital emergency services (fully variable, fully fixed, and mixed
      variable/fixed) in terms of the key products and cost drivers in the ED.
      Approaches to the setting and rebasing of fixed grants are considered. Problems
      of potential incentive effects and double payment for admitted patients make the
      setting of variable payments problematic, particularly for patients subsequently
      admitted as inpatients. Key characteristics of an ED funding model in single
      payer systems are proposed.

PMID- 11223769
TI  - Traumatic brain injury outcome: concepts for emergency care.
AB  - Injury to the brain is the leading factor in mortality and morbidity from
      traumatic injury. The devastating personal, social, and financial consequences of
      traumatic brain injury (TBI) are compounded by the fact that most people with TBI
      are young and previously healthy. From the emergency physician's standpoint,
      patients with severe TBI are those with a presenting Glasgow Coma Scale score of
      less than 9. Over the past 30 years, mortality from severe traumatic brain injury
      for those patients who survive to the hospital has been reduced by half from
      nearly 50% to approximately 25%. Because most of the pathologic processes that
      determine outcome are fully active during the first hours after TBI, the
      decisions of emergency care providers may be crucial. This review addresses new
      concepts and information in the pathophysiology of TBI and secondary brain injury
      and demonstrates how emergency management may be linked to neurologic outcome.

PMID- 11223770
TI  - Two separate unintentional fatalities with the same revolver.
AB  - We report 2 deaths and 1 injury that resulted from 2 separate unintentional
      discharges of the same Ruger Blackhawk revolver. One discharge was a consequence
      of careless firearm handling combined with a slip during a decocking procedure
      unique to certain hammer-action firearms. The second discharge occurred when the
      firearm was dropped and was the result of a combination of firearm design and a
      lack of knowledge regarding the safe handling of this type of revolver. The
      second death may have been prevented by the timely intervention of a health care
      or law enforcement professional at the time of the first unintentional discharge.
      Physicians who become knowledgeable about the functioning of different types of
      firearms and how they can malfunction may help promote the safe and responsible
      use of firearms among their patients.

PMID- 11223771
TI  - Single-payer and all-payer systems: implications for emergency medicine in the
      United States.

PMID- 11223772
TI  - Three shots, two dead, five errors, one gun: a recipe for prevention?

PMID- 11223773
TI  - The education of researchers-big brother, watching.

PMID- 11223774
TI  - Computed tomography for subarachnoid hemorrhage: what should we make of the
      "evidence"?

PMID- 11223775
TI  - Update on emerging infections from the Centers for Disease Control and
      Prevention. Varicella outbreaks among Mexican adults--Alabama, 2000.

PMID- 11223777
TI  - Death of a difficult patient.

PMID- 11223778
TI  - Where they don't value life.

PMID- 11223779
TI  - Fomepizole in ethylene glycol intoxication.

PMID- 11223780
TI  - Perspectives on medical malpractice.

PMID- 11223782
TI  - Succinylcholine-assisted endotracheal intubation by paramedics.

PMID- 11223784
TI  - Endotracheal tube introducer.

PMID- 11223785
TI  - Endotracheal tube introducer.

PMID- 11223787
TI  - Emergency physician rights and responsibilities.

PMID- 11223789
TI  - The pig in the python: baby boomers.

PMID- 11223791
TI  - Into the new age: the call for a new construct for nursing.

PMID- 11223792
TI  - Osteoporosis overview.
AB  - Osteoporosis, a disease characterized by low bone mass, microarchitectural
      deterioration of bone, and susceptibility to bone fractures, can lead to
      debilitating pain and deformity. The disease represents a major health problem,
      particularly in older women. Approximately 1.5 million people in the United
      States suffer osteoporosis-related fractures annually, and many never gain full
      recovery. The direct annual health expenditures related to osteoporosis fractures
      were estimated at $13.3 billion in 1994, but quality of life costs related to
      osteoporosis are even more profound. Identifying people at risk for osteoporosis
      and early treatment can minimize its destructive effects. Nurses play an
      important role in the development of strategies to reduce the incidence of
      osteoporosis and osteoporosis-related fractures, pain, and deformity to help
      older adults lead healthy, productive lives in their later years.

PMID- 11223793
TI  - Hormonal decline in elderly men and male menopause.
AB  - Much has been written about female menopause, but hormonal decline in men
      indicative of a similar menopause is a relatively new concept. Hormonal decline
      in men is a gradual and often occult process. Many men do not experience
      noticeable symptoms, but those who do usually experience a decline in sexual
      desire and ability that may be attributed to aging. Some men may hide these
      symptoms. Hormonal replacements and herbal therapies may be helpful. Nurses must
      conduct careful histories and physical examinations to elicit disclosure of
      symptoms of hormonal decline in this population.

PMID- 11223794
TI  - Enhancing mastery and sense of coherence: important determinants of health in
      older adults.
AB  - The purpose of the study was to expand existing knowledge of the determinants of
      health for community-dwelling young-old and old-old people. A subsample (n =
      2413) from the Health Canada Supplement to the 1994 National Population Health
      Survey was analyzed. The factors examined were biographic attributes,
      sociodemographic indicators, sense of coherence (SOC), mastery, self-esteem,
      informal social support, and use of health care services. Hierarchical regression
      analyses revealed that mastery and SOC were strongly related to health status and
      perceived health. Strategies discussed herein will help practitioners ensure that
      older adults' mastery and SOC are supported and enhanced.

PMID- 11223795
TI  - Mammography screening behavior in older women caregivers.
AB  - The purposes of this study are to explore older caregivers' mammography
      participation and the facilitators and barriers to mammography screening. Of the
      52 older female caregivers with a mean age of 65 years (range 50-90) interviewed
      by telephone, 80.8% had had a mammogram within 12 months. Significant
      facilitators included health care provider recommendation and beliefs in the
      efficacy of treatment. Significant barriers included health care providers'
      failure to recommend mammograms, caregiver procrastination, fear of pain, and
      lack of symptoms. Caregivers with higher burden reported less frequent self- and
      provider-conducted breast examinations.

PMID- 11223796
TI  - Nickelodeon in the new millennium.

PMID- 11223797
TI  - Caring for the aging athlete.

PMID- 11223799
TI  - Nutritional strategies efficacious in the prevention or treatment of coronary
      heart disease (CHD).

PMID- 11223800
TI  - In memoriam: Robert W. Bell, November 22, 1931- September 16, 2000.

PMID- 11223801
TI  - The effect of cholinergic stimulation on rat pup ultrasonic vocalizations.
AB  - As cholinergic stimulation increases vocalizations in adult rats, the present
      study investigated the effects of systemic oxotremorine, a cholinergic agonist,
      on the production of separation calls in rat pups of different ages and whether
      these effects are in response to central versus peripheral stimulation. The first
      experiment examined the dose-response effects of oxotremorine on the number of
      vocalizations and acoustic parameters of 10-, 15-, and 17-day-old rat pups. In
      contrast to other studies on adult rats, pup vocalizations were decreased while
      marginally changing acoustic parameters. The second experiment, using muscarinic
      antagonists, showed that pretreatment with atropine sulfate, which can cross the
      blood-brain barrier (BBB), reversed the call-reducing effect of oxotremorine
      whereas pretreatment with atropine methyl nitrate, which does not cross BBB, did
      not. Suppression of vocalizations by oxotremorine may be explained by central
      activation and not the peripheral effects of the drug. Dissimilar effects of
      cholinergic stimulation of infant and adult rat brains may be attributed to a
      differential role of the cholinergic system during development and maturity.

PMID- 11223802
TI  - Social interaction with an intoxicated sibling can result in increased intake of
      ethanol by periadolescent rats.
AB  - A novel procedure for enhancing voluntary intake of ethanol in periadolescent
      rats is described. The procedure is a modification of Galef et al.'s (e.g.,
      Galef, Kennett, & Stein, 1985; Anim Learn Behave 13:25-30) demonstrator-observer
      procedure. Subjects were Sprague-Dawley rats, 28-35 days of age. The experimental
      subject (observer) interacted with a same-sex conspecific (demonstrator)
      previously administered (a) 1.5 g/kg ethanol, (b) an equal volume of water, or
      (c) 2.1% Sanka coffee intragastrically. Observers were tested with 24-hour access
      to ethanol and coffee solutions. Observers that had interacted with demonstrators
      administered ethanol ingested significantly more ethanol during the test than
      observers in the other two groups. In Experiment 2 demonstrators were
      administered one of several doses of ethanol (0.0, 1.0, 1.5, or 3.0 g/kg) and
      observers' ethanol intakes were assessed. Only those observers that interacted
      with 1.5 g/kg demonstrators increased their ingestion of ethanol, relative to
      water controls. The lower (1.0 g/kg) and higher (3.0 g/kg) dose groups did not
      show altered ethanol ingestion. These results are discussed with respect to
      threshold levels of respired ethanol cues and the ability of observers to detect
      these cues from demonstrators. The demonstrator-observer procedure appears to be
      effective for the social transmission of preferences for ethanol in
      periadolescent rats.

PMID- 11223803
TI  - Stress correlates of hand preference in rhesus macaques.
AB  - In this research we examined stress-related correlates of hand preference in
      monkeys. Specifically, we tested the hypothesis that stress reactivity and plasma
      levels of the stress hormone cortisol are developmentally related to handedness
      in rhesus macaques (Macaca mulatta). We found a significant positive correlation
      between cortisol levels sampled in juveniles and the frequency of right- versus
      left-hand use sampled in these same animals during adulthood. Right-hand
      preference was negatively correlated with stress reactivity. These data are
      consistent with the view that stress functioning and reactivity are associated
      with the development of hemispheric specialization in primates.

PMID- 11223804
TI  - Plasma cortisol is associated with handedness in infant rhesus monkeys.
AB  - In this research we examined the relationship between plasma cortisol and
      handedness in infant rhesus macaques (Macaca mulatta). Specifically, we tested
      the hypothesis that stress functioning is related to hemispheric specialization
      and manifested in a positive correlation between cortisol levels and the
      frequency of right- versus left- hand use. We found a significant positive
      relationship between cortisol levels sampled at ages 1 and 3 months and lateral
      bias toward greater use of the right hand versus left hand sampled between ages 4
      and 11 months. Further, we found a significant negative relationship between
      cortisol sampled at age 5 months and strength of lateral bias (independent of
      direction). These data suggest an early developmental influence of stress
      functioning on hemispheric specialization for manual control in infant monkeys.

PMID- 11223805
TI  - Modulation of manual activity by vision in human newborns.
AB  - This experiment investigates neonatal intersensory functioning between touch and
      vision for texture density. The experiment compared manual activity (holding time
      and hand pressure frequency) recorded on objects in the presence (test period) or
      absence of visual information (pre-test and post-test periods). Thirty-two babies
      were assigned to four experimental conditions according to texture density of the
      objects held and seen during the test period: Objects had either the same
      (matching conditions) or different (mismatching conditions) texture density
      information. The results clearly showed that in matching conditions, holding
      times were systematically increased during the test period. However, hand
      pressure frequency remained unchanged over the three test periods. In the
      mismatching conditions, holding times remained unchanged over the three test
      periods. However, hand pressure frequency systematically changed during the test
      period according to the texture density of the visual object. These results
      indicate newborns' capability to compare texture density information across
      modalities.

PMID- 11223806
TI  - Activity patterns assessed throughout 24-hour recordings in preterm and near term
      infants.
AB  - The motility of 10 low-risk infants, aged between 34 and 40 weeks of
      postmenstrual age, has been continuously recorded for 24 h. Four codes were
      distinguished: code 1 (absence of motility or occasional occurrence of startles),
      code 2 (presence of small general or isolated body movements, startles, smiles,
      grimaces, and other facial activity), code 3 (forceful and prolonged general
      movements, startles, and stretches), code 4 (vigorous and abrupt general body
      movements accompanied by crying). Changes with age concern mainly the increase of
      the duration of code 1 (quiescence) episodes. Confrontation between day and night
      showed higher levels of motility during the night than during the day. The last
      weeks before term represent a time for increase in the ability to sustain a quiet
      behavior and to reorganize day-night motility distribution.

PMID- 11223808
TI  - Evidence for two distinct mechanisms of neurogenesis and cellular pattern
      formation in regenerated goldfish retinas.
AB  - After its destruction by intraocular injection of ouabain, the goldfish retina
      regenerates, but little is known about the histogenesis of the new tissue,
      including the structure and formation of regenerated cell mosaic patterns. In an
      effort to determine how retinal cells are generated and spatially organized
      within retina regenerated after ouabain injection, in situ hybridization and
      immunocytochemical techniques were combined with computational analyses of two
      dimensional spatial patterns of identified neurons. Labeling with specific opsin
      riboprobes revealed two distinct cone patterns in the ouabain-injected eyes, each
      of which was different from the relatively orderly cone patterns of native
      retina. Central, regenerated regions had sparse aggregates of cones, and a
      relatively lower density of each cone type. Peripheral regions of experimental
      retina, likely derived from the circumferential germinal zone, had high densities
      of all cone types, each of which tended to be distributed randomly. The spatial
      patterns of inner retinal neurons in experimental eyes were also disorganized
      with respect to native retina. These results indicate that although some aspects
      of retinal regeneration resemble normal retinal development and growth, ouabain
      induced regeneration does not produce well-organized mosaics of neurons,
      indicating a failure of the developmental interactions needed for proper pattern
      formation, which in turn could compromise visual recovery. Furthermore, the
      distinct cone patterns in different regions of experimental retina support the
      hypothesis that new goldfish retina arises via two spatially and cellularly
      distinct mechanisms after exposure to ouabain.

PMID- 11223809
TI  - Hypoxic/ischemic insult alters ferritin expression and myelination in neonatal
      rat brains.
AB  - Ferritin is expressed very early in the development of oligodendrocytes. This
      protein makes iron available within cells while providing some protection from
      iron-induced oxidative damage. In the developing rat brain, ferritin is found
      initially in microglia followed by oligodendrocytes in a temporal and spatial
      pattern that coincides with the expression of myelin. In this study, we test the
      hypothesis that hypoxic/ischemic (H/I) insult will alter the expression of
      ferritin in microglia and oligodendrocytes, resulting in a delay in the
      appearance of myelin markers. Seven-day-old rat pups were exposed to H/I insult.
      Within 24 hours, after the insult, there is an increase in ferritin-positive
      amoeboid microglia and a decrease in immunohistochemical reaction for the myelin
      marker Rip in the brain. The oligodendrocyte marker 2'-3'-cyclic nucleotide 3'
      phosphodiesterase is elevated in the H/I hemisphere relative to the hypoxia-only
      hemisphere between 8 and 15 days after insult. By 23 days after the insult, the
      subcortical white matter segregates into areas that contain ferritin-positive
      microglia and are devoid of Rip-positive oligodendrocytes or areas with Rip
      positive cells and no ferritin-positive microglia. The H/I insult also affects
      the ratio of H-rich to L-rich ferritin expression at most of the time periods.
      These results demonstrate that the type of ferritin, its cellular distribution
      and the normal pattern of subcortical white matter myelination is affected by
      H/I. We propose that the absence of ferritin in oligodendrocytes prohibits them
      from storing sufficient iron to meet the synthetic and metabolic demands
      associated with myelination.

PMID- 11223810
TI  - Nerve growth factor induces light adaptive cellular and synaptic plasticity in
      the outer retina of fish.
AB  - Recent evidence suggests that neurotrophins can be involved in short-term
      synaptic plasticity in parts of the central nervous system. In the present study,
      the possible role of nerve growth factor (NGF) in inducing morphologic (cellular
      and subcellular) changes in the outer retina of carp was assessed. The effects of
      NGF on cone photomechanical movements (PMMs) and horizontal cell (HC) spinule
      formation were measured. NGF-induced cone contraction and formation of HC
      spinules in the dark-adapted retina were consistent with its role in light
      adaptation. These effects were dose dependent in the range of 5--250 nM. Because
      cone contraction and HC spinule formation have previously been shown to be
      controlled by dopamine (DA), nitric oxide (NO), or both, the possibility that the
      effects of NGF could be occurring by means of release of DA and/or NO was tested.
      Haloperidol (HAL), a nonspecific DA receptor blocker, or 2-(4-carboxyphenyl)
      4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide potassium (cPTIO), a NO scavenger,
      was applied in combination with NGF to dark-adapted eyecups. The results showed
      that both HAL and cPTIO significantly blocked the effects of NGF on cone PMMs and
      HC spinule formation. In conclusion, (1) NGF represents a novel light-adaptive
      signalling mechanism in the outer retina of fish; and (2) NGF-induced cone
      contraction and HC spinule formation in the retina together with our previous
      observation would suggest that the effects of NGF may be mediated through NO by
      means of DA.

PMID- 11223811
TI  - Parasympathetic and sympathetic control of the pancreas: a role for the
      suprachiasmatic nucleus and other hypothalamic centers that are involved in the
      regulation of food intake.
AB  - To reveal brain regions and transmitter systems involved in control of pancreatic
      hormone secretion, specific vagal and sympathetic denervation were combined with
      injection of a retrograde transsynaptic tracer, pseudorabies virus (PRV), into
      the pancreas. After sympathetic or vagal transsection first-order neurons were
      revealed in the dorsal motor nucleus of the vagus (DMV) or in preganglionic
      spinal cord neurons (SPN), respectively. Careful timing of the survival of the
      animals allowed the detection of cell groups in immediate control of these DMV or
      SPN neurons. A far larger number of cell groups is involved in the control of DMV
      than of SPN neurons. Examples are given of a high level of interaction between
      the sympathetic and parasympathetic nervous system. Several cell groups project
      to both branches of the autonomic nervous system, sometimes even the same
      neurotransmitter is used, e.g., oxytocin neurons in the paraventricular nucleus
      and melanin-concentrating hormone and orexin neurons in the lateral hypothalamus
      project to both the DMV and SPN neurons. Moreover, the appearance of third-order
      neurons located in the sympathetic SPN after complete sympathectomy and in the
      DMV after complete vagotomy illustrates the possibility that motor neurons of the
      sympathetic and parasympathetic system may exchange information by means of
      interneurons. The presence of second-order neurons in prefrontal, gustatory, and
      piriform cortex may provide an anatomic basis for the involvement of these
      cortices in the cephalic insulin response. The observation that second-order
      neurons in both vagal and sympathetic control of the pancreas contain
      neuropeptides that are known to play a role in food intake indicates a direct
      association between behavioral and autonomic functions. Finally, the observation
      of third-order neurons in the suprachiasmatic nucleus and ventromedial
      hypothalamus shows the modulatory action of the time of the day and metabolic
      state, respectively.

PMID- 11223812
TI  - Vesicle-associated membrane protein isoforms in the tiger salamander retina.
AB  - Vesicle associated membrane protein (VAMP; also known as synaptobrevin) is a key
      component of the core complex needed for docking and fusion of synaptic vesicles
      with the presynaptic plasma membrane. Recent work indicates that the precise
      complement of presynaptic proteins associated with transmitter release and their
      isoforms vary among synapses, presumably conferring specific functional release
      properties. The retina contains two types of vesicular synapses with distinct
      morphologic, functional, and biochemical characteristics: ribbon and conventional
      synapses. Although the precise complement of presynaptic proteins is known to
      differ between conventional and ribbon synapses and among conventional synapses,
      the distribution of VAMP isoforms among retinal synapses has not been determined.
      The expression and localization of VAMP isoforms in the salamander retina, a
      major model system for studies of retinal circuitry, was examined by using
      immunocytochemical and immunoblotting methods. Both methods indicated that at
      least two VAMP isoforms were expressed in salamander retina. One isoform,
      recognized by an immunoglobulin M antibody that recognizes both mammalian VAMP-1
      and VAMP-2, was associated with photoreceptor and bipolar cell terminals as well
      as many conventional synapses, and probably corresponds to mammalian VAMP-2. A
      different VAMP isoform associated with a subset of amacrine cells, was recognized
      only by antibodies directed against the N-terminus of mammalian VAMP-2. An
      antiserum directed against the N-terminus of mammalian VAMP-1 did not
      specifically recognize any salamander VAMPs in either immunocytochemical or
      immunoblotting experiments. Heterogeneous distribution of VAMP isoforms among
      conventional retinal synapses was confirmed by double labeling for synapsin I, a
      marker for conventional synapses. These studies indicate that VAMP isoforms are
      expressed heterogeneously among retinal synapses but cannot account for the
      differences in transmitter release characteristics at ribbon and conventional
      synapses. These results also corroborate previous studies in Xenopus indicating
      that the N-terminus of nonmammalian VAMP isoforms differs from their mammalian
      counterparts.

PMID- 11223813
TI  - Age-related change in the number of neurons in the human vestibular ganglion.
AB  - Dysequilibrium of aging in humans has been speculated to arise from progressive
      deterioration within anatomical components of the vestibular system. An integral
      part of this system is vestibular ganglions, which are bipolar neurons that relay
      peripheral vestibular information to the central nervous system. To assess the
      effect of aging on the number of human vestibular ganglion neurons, assumption
      free stereology in the form of the optical fractionator was used on 20 serially
      sectioned archival human temporal bone specimens. Donors had no history of
      vestibular pathology and ranged in age from 2 to 88 years. An average of 25,812
      (coefficient of variation = 0.13) vestibular ganglion neurons was found
      throughout this age range, a significant departure from the results of past
      studies. Logistics-based regression analysis pointed to a nonlinear pattern of
      decline in the neuronal population: the number of cells remained roughly constant
      at about 28,952 cells in youth and then declined gradually between 30 and 60
      years of age before leveling off at approximately 23,349 cells in older
      individuals. This study confirmed the existence of an age-related decline in the
      primary neurons of the human vestibular system, thus providing one anatomical
      basis for the increased incidence of imbalance seen with age.

PMID- 11223814
TI  - Administration of tamoxifen but not flutamide to hormonally intact, adult male
      rats mimics the effects of short-term gonadectomy on the catecholamine
      innervation of the cerebral cortex.
AB  - Gonadectomy in adult male rats induces a series of changes in cortical
      catecholamine innervation that begins with a large, but transient decrease in the
      density of tyrosine hydroxylase- but not dopamine-beta-hydroxylase-immunoreactive
      axons in sensory, motor, and association cortices. More recent studies have shown
      that estradiol maintains these presumed dopamine afferents but that supplementing
      acutely gonadectomized rats with dihydrotestosterone provides no protective
      effects for innervation. These findings suggest that the depression of
      mesocortical dopamine axons that follows gonadectomy is stimulated by changes in
      estrogen signaling. The studies presented here examined tyrosine hydroxylase and
      dopamine-beta-hydroxylase innervation in hormonally intact adult male rats
      treated for 4 days with the nonsteroidal antiestrogen tamoxifen or with the
      nonsteroidal antiandrogen flutamide to probe for additional evidence for this
      selective hormone sensitivity and for insights into the intracellular mechanisms
      that may govern it. Qualitative and quantitative comparisons of innervation with
      corresponding data from control and acutely gonadectomized rats revealed that
      administration of the antiestrogen tamoxifen in hormonally intact rats produced
      deficits in catecholamine innervation that mirrored those induced by short-term
      gonadectomy. The antiandrogen flutamide, however, had no discernible impact on
      cortical afferents. When considered within the context of the known pharmacology
      and sites of action of tamoxifen, these findings not only provide additional
      support for an initial phase of selective estrogen sensitivity among the cortical
      catecholamines but also suggest that it is stimulation of intracellular estrogen
      receptors that confers this sensitivity in the adult rat cerebrum.

PMID- 11223815
TI  - Glial fibrillary acidic protein-immunopositive structures in the brain of a
      Crocodilian, Caiman crocodilus, and its bearing on the evolution of astroglia.
AB  - Caiman crocodilus, as a representative of the order Crocodilia, was used in
      immunohistochemical studies. Immunohistochemical procedures were performed on
      free-floating sections using a monoclonal antibody against porcine glial
      fibrillary acidic protein (GFAP) and employing standard avidin-biotin complex
      methodology. The astroglia of Caiman exhibited robust immunoreactivity to the
      antibodies raised against mammalian GFAP. In Caiman, the predominant GFAP
      immunopositive elements are the radial ependymoglia, similar to other reptiles.
      The regional variability of glial architecture in Caiman, however, seems greater
      than in other reptiles so far examined, although it is less compared with
      chickens. We suggest that this finding corresponds to a more advanced "regional
      adaptation" of the glial structure in Caiman compared with other reptiles. The
      main feature that distinguishes the astroglia of Caiman from those of other
      reptiles is the widespread occurrence of GFAP-immunopositive astrocytes. These
      cells are limited in lizards and snakes, are not present in turtles, but are
      found in every major brain area in Caiman. However, even in Caiman, astrocytes
      are only intermingled with radial glia and are not the predominant glial element
      of any brain area. The occurrence of astrocytes does not correlate with brain
      wall thickness. Despite their origin from different ancestral groups of stem
      reptiles (synapsid or diapsid), mammals and birds exhibit some common general
      features in their glial architecture and GFAP distribution: 1) predominance of
      astrocytes and 2) absent or limited GFAP immunopositivity of several brain areas.
      The present study demonstrates that, even in Caiman, a representative of the
      reptilian group most closely related to birds, these features are present only in
      part, suggesting that, in mammals and birds, they have evolved independently.

PMID- 11223816
TI  - Innervation of the ring gland of Drosophila melanogaster.
AB  - In insects, peptidergic neurons of the central nervous system regulate the
      synthesis of the main developmental hormones. Neuropeptides involved in this
      neuroendocrine cascade have been identified in lepidopterans and dictyopterans.
      Since these organisms are not suitable for genetic research, we identified
      peptidergic brain neurons innervating the ring gland in Drosophila melanogaster.
      In larvae of Drosophila, ecdysteroids and juvenile hormones are produced by the
      ring gland, which is composed of the prothoracic gland, the corpus allatum, and
      the corpora cardiaca. Using the GAL4 enhancer trap system, we mapped those
      neurons of the central nervous system that innervate the ring gland. Eleven
      groups of neurosecretory neurons and their target tissues were identified. Five
      neurons of the lateral protocerebrum directly innervate the prothoracic gland or
      corpus allatum cells of the ring gland and are believed to regulate ecdysteroid
      and juvenile hormone titers. Axons of the circadian pacemaker neurons project
      onto dendritic fields of these five neurons. This connection might be the
      neuronal substrate of the circadian rhythms of molting and metamorphosis in
      Drosophila. Most of the neurons presented here have not been described before.
      The enhancer trap lines labeling them will be valuable tools for the analysis of
      neuronal as well as genetic regulation in insect development.

PMID- 11223817
TI  - Multivisceral resections for colorectal cancer.

PMID- 11223818
TI  - Factors influencing choice between mastectomy and lumpectomy for women in the
      Carolinas.
AB  - BACKGROUND AND OBJECTIVES: The Carolinas have been documented to have a low rate
      of breast-conserving surgery. The purpose of this study was to determine factors
      that influence women's choice between mastectomy and lumpectomy. METHODS: An
      anonymous questionnaire was designed for the study and was mailed to women on the
      mailing lists of cancer organizations in North and South Carolina. Women who had
      initially been treated in 1995-1998 were included. RESULTS: The rate of breast
      conserving surgery (BCS) was 18% and actually declined from a high of 23% in
      1995. The highest rate of BCS was in private hospitals rather than academic
      health science centers. Fifty-four of the 212 respondents believed they were
      given a choice between mastectomy and BSC and, of these, only 15% (n = 80) chose
      BSC. Women in the two treatment groups differed in education and income. Sources
      of treatment-related information included cancer organizations, popular media,
      friends, family, and the Internet. The most important factor to both groups was
      perceived probability of cure. Avoidance of radiation treatments was a factor
      among the mastectomy group. CONCLUSIONS: The low rate of BCS for the region was
      confirmed. Many women are still unconvinced that BSC offers as great a likelihood
      of cure as mastectomy.

PMID- 11223819
TI  - Highly sensitive immunohistological study for detection of estrogen receptor in
      human breast cancer.
AB  - BACKGROUND: Immunohistological methods for the detection of estrogen receptor in
      human breast cancer using formalin-fixed, paraffin-embedded tissue not only have
      the advantages of being cheaper and requiring less tissue but also have several
      theoretical advantages. For example, such methods enable direct histological
      visualization of the assessed tissue and thereby reduce sampling error.
      Traditional immunohistological methods (traditional LSAB), however, show false
      negative reactions more often than the enzyme-binding immunoassay method (EIA).
      METHODS: After determining 25 estrogen receptor-positive cases and 50 estrogen
      receptor-negative cases by EIA, we analyzed these same cases using a traditional
      LSAB method and a new highly sensitive immunohistological method for assaying
      formalin-fixed, paraffin-embedded tissue. RESULTS: Using this new method, we
      detected 10 instances of positive estrogen receptors among the 50 EIA receptor
      negative cases. The 25 EIA-positive cases were positive for estrogen receptor
      antigen except 1case using the new method. CONCLUSIONS: This new method not only
      has the advantage of use in paraffin-embedded tissue but also is more sensitive
      than the EIA. We recommend this new method as a choice to decrease false
      negatives.

PMID- 11223820
TI  - Rat glioma cell death induced by cationic liposome-mediated transfer of the
      herpes simplex virus thymidine kinase gene followed by ganciclovir treatment.
AB  - BACKGROUND AND OBJECTIVES: We studied antitumor effects and cell death induced by
      cationic liposome-mediated gene transfer of the herpes simplex virus thymidine
      kinase (HSV-tk) gene followed by ganciclovir treatment in cultured rat T9 glioma
      cells and in experimental gliomas produced from this cell line. METHODS: To
      transfer genes we used small unilamellar cationic liposomes containing N-(alpha
      trimethylammonioacetyl)-didodecyl-D-glutamate chloride. Video-enhanced contrast
      differential interference contrast microscopy was used for morphologic
      observations of cultured cells. RESULTS: When we treated the cells or implanted
      gliomas with the liposomes and ganciclovir, a strong effect was seen against
      tumor cells, and survival of tumor-implanted rats was increased. Morphologically,
      cell death observed after HSV-tk gene/liposome and ganciclovir treatment in the
      cultured glioma cells included both apoptosis and necrosis. CONCLUSIONS:
      Introduction of the HSV-tk gene in a DNA-liposome complex followed by ganciclovir
      treatment induced both apoptosis and necrosis, which together resulted in a
      potent antitumor effect.

PMID- 11223821
TI  - Expression of cyclooxygenase-2 in human gastric adenomas and adenocarcinomas.
AB  - BACKGROUND AND OBJECTIVES: The increased expression of cyclooxygenase (COX)-2 has
      been implicated in the development and progression of colorectal cancer. We
      sought to determine the involvement of COX-2 in human gastric cancer. MATERIALS
      AND METHODS: COX-2 mRNA was assayed in both gastric cancer cell lines and biopsy
      specimens from 37 gastric adenocarcinomas, five gastric adenomas, and five
      hyperplastic polyps by reverse transcription-polymerase chain reaction. RESULTS:
      COX-2 mRNA was found in four of five gastric cancer cell lines, two from
      intestinal type and two from diffuse type. COX-2 mRNA was expressed in 19 of 37
      (51%) human gastric cancer specimens. The tumor diameter was greater in patients
      with COX-2 expression than in those without (6.5 +/- 4.6 vs. 3.8 +/- 2.7 cm, P <
      0.05). The incidence of COX-2 mRNA expression was significantly higher in
      patients with pT2-pT4 tumors than in those with pT1 tumors (71 vs. 35%, P <
      0.05). Significantly higher expression of COX-2 mRNA was also observed in
      patients with lymph node involvement than in those without (75 vs. 40%, P <
      0.05). COX-2 mRNA was found in one of five adenomas, while it was absent in five
      hyperplastic polyps. The paired normal gastric musosa did not express COX-2 mRNA
      in any of the 47 patients. CONCLUSIONS: These results provide clinical evidence
      that COX-2 may contribute to tumor progression in human gastric adenocarcinoma.

PMID- 11223822
TI  - Prognostic significance of expression of thymidine phosphorylase and vascular
      endothelial growth factor in human gastric carcinoma.
AB  - BACKGROUND AND OBJECTIVES: Both thymidine phosphorylase (dThdPase) and vascular
      endothelial growth factor (VEGF) are well-characterized inducers of angiogenesis.
      The purpose of this study was to examine the expression of these antigens and
      their prognostic significance in gastric carcinoma. METHODS: Medical records of
      102 patients with stage II tumor were retrospectively reviewed. Primary tumors
      were studied by immunohistochemical staining for dThdPase and VEGF. RESULTS:
      Positive dThdPase expression was observed in 52 (51%) tumors and positive VEGF
      expression in 53 (52%) tumors. There was a significant correlation between the
      positive expression of VEGF and lymphatic invasion. The patients with dThdPase
      positive carcinoma showed a significantly worse prognosis than those with
      dThdPase-negative carcinoma in stage II. Moreover, the frequency of hepatic
      recurrence was significantly higher in the patients with dThdPase-positive and
      VEGF-positive tumors than in those with dThdPase-negative and VEGF-negative
      tumors. CONCLUSIONS: Combination analysis of dThdPase and VEGF expression in
      gastric carcinoma appears to be well-characterized inductors of prognosis and
      metastasis.

PMID- 11223823
TI  - Clinicopathologic study of mixed hepatocellular and cholangiocellular carcinoma:
      modes of spreading and choice of surgical treatment by reference to macroscopic
      type.
AB  - BACKGROUND AND OBJECTIVES: Clinicopathologic features and the choice of surgical
      treatment for mixed hepatocellular and cholangiocellular carcinoma (MHC) remain
      controversial. METHODS: We evaluated the clinicopathological features of seven
      cases of MHC (one autopsied and six surgically resected cases). MHCs were divided
      into two classes by reference to macroscopic appearance: four were of the single
      nodular (SN) type and three were of the multinodular (MN) type. RESULTS: The mean
      age of patients and mean preoperative level of serum alpha-fetoprotein were 44.5
      years and 56,457 ng/ml for the SN type and 63.7 years and 1,227 ng/ml for the MN
      type, respectively. Histologically, invasion of the portal vein, the hepatic
      vein, and the perineural space was found in three, two, and zero cases of SN type
      tumors and in three, three, and one cases of MN type tumors, respectively. Lymph
      node metastases were found only in two patients with MN type MHC. CONCLUSIONS:
      MHC of the SN type had a pattern of infiltration similar to hepatocellular
      carcinoma. By contrast, MHC of the MN type resembled intrahepatic
      cholangiocellular carcinoma. It is suggested that lymphadenectomy might be
      necessary for treatment of selected MHC, in particular MHC with a multinodular
      appearance.

PMID- 11223824
TI  - Pulmonary metastasectomy: might the type of resection affect survival?
AB  - BACKGROUND AND OBJECTIVES: Metastasectomy proved to be the choice treatment in
      the case of pulmonary metastasis. In this study we assessed the impact on
      survival of three types of resection: minimal by laser or conventional device and
      lobectomy. METHODS: We considered 85 patients who underwent lung metastasectomy
      for tumors that originated from various sites. Fifty-two minimal resections were
      accomplished in 34 patients by conventional (diathermy dissection or stapler
      suture line) device, 59 resections in 29 by Nd:YAG laser. Lobectomies were 22.
      Minimum follow up required was 2 years. RESULTS: The 3-year Kaplan-Meier survival
      rate was 63%, 44%, 53% for laser, conventional resections and lobectomy. The 5
      year survival was 40%, 28%, 26% respectively. Among the groups there was no
      significant difference (P = 0.15). Laser patients showed shorter periods of air
      leakage and hospital stay. CONCLUSIONS: The type of resection did not disclose
      statistically significant differences on survival. Minimal surgery, especially by
      laser device, is recommended for less morbidity.

PMID- 11223825
TI  - Clinicopathological characteristics of surgically resected lung cancer associated
      with idiopathic pulmonary fibrosis.
AB  - BACKGROUND AND OBJECTIVES: Idiopathic pulmonary fibrosis (IPF) is well known to
      be associated with lung cancer. It is important to clarify the clinical and
      pathological features of lung cancer with IPF in understanding the pathogenesis
      of lung cancer in IPF patients. We compared clinicopathological factors of lung
      cancer in patients with and without IPF. METHODS: A retrospective study was
      conducted in 711 surgically resected lung cancer patients. Medical records were
      compared of IPF and non-IPF patients. RESULTS: Of the 711 patients, 53 (7.5%)
      were IPF patients. Lung cancer in IPF patients was more frequent in elderly male
      smokers. Most lung cancers in IPF (79%) arose in peripheral areas involving
      fibrosis (P < 0.01). The incidence of squamous cell carcinoma in the IPF patients
      (46%) was significantly higher than that in non-IPF patients (22%) (P < 0.01).
      The incidence of multiple lung cancer in IPF cases (17%) was also significantly
      higher. CONCLUSIONS: These results suggest that IPF has the potential to develop
      into lung cancer, especially peripheral squamous cell carcinoma. Further
      molecular analyses are necessary to clarify the relationship between IPF and lung
      cancer.

PMID- 11223826
TI  - Reappraisal of the role of NM23-H1 in colorectal cancers.
AB  - BACKGROUND AND OBJECTIVES: A number of evidence indicate that downregulation of
      the nm23-H1 gene may be relevant to metastatic progression of many kinds of human
      cancer. However, its role in colorectal cancers remains controversial. To address
      the issue, this study was performed to investigate the clinical relevance of nm23
      H1 in patients with colorectal cancers. METHODS: Immunohistochemical expression
      of nm23-H1 protein product (NM23-H1) was studied in a total of 146 colorectal
      cancer patients and compared for its prognostic value at a mean follow-up of 54
      months. RESULTS: There was no apparent correlation between NM23-H1 expression and
      clinicopathological indicators, including Dukes category, lymphatic metastasis,
      distant metastasis, histological grading, and tumor location (P < 0.1,
      respectively). In addition, determination of NM23-H1 expression status did not
      provide independent prognostic information compared with conventional
      pathological staging. CONCLUSIONS: The results indicate that nm23-H1 gene does
      not play an important part in the progression of colorectal carcinogenesis.

PMID- 11223827
TI  - Expression of Fas ligand is an early event in colorectal carcinogenesis.
AB  - BACKGROUND AND OBJECTIVES: Fas ligand (FasL) is expressed in many cancers and
      plays an important role in establishing immunologically privileged environments
      that allow tumors to escape the host's immune surveillance. We investigate the
      expression of FasL in human colorectal cancer and colorectal adenoma and
      elucidate the relationship between FasL expression and the clinicopathological
      characteristics of colorectal cancers. METHODS: We examined 214 colorectal cancer
      specimens and 83 colorectal adenoma specimens. Expression of FasL was determined
      by immunohistochemical staining using a specific monoclonal antibody. We analyzed
      the relationship between the results of FasL expression and clinicopathological
      data statistically. RESULTS: FasL expression was detected in 173 (80.8%) of 214
      colorectal carcinomas and 34 (40.9%) of 83 colorectal adenomas. The status of
      FasL expression in colorectal carcinoma was independent of clinicopathological
      features including tumor stage, histologic grade, lymphatic invasion, venous
      invasion, lymph node metastasis, liver metastasis, and Dukes stage. In colorectal
      adenoma, FasL expression was more frequently observed in high-grade atypia than
      in low-grade atypia (P = 0.05). CONCLUSIONS: FasL expression is commonly observed
      not only in cancer but also in highly dysplastic tissue. These observations
      suggest that FasL expression may be an important event in the transformation
      process leading to adenocarcinoma.

PMID- 11223829
TI  - Fertility preserving testicular transposition in patients undergoing inguino
      pelvic irradiation.

PMID- 11223830
TI  - Interstitial laser thermotherapy in the treatment of colorectal liver metastases.
AB  - Metastatic liver disease is the commonest cause of death in patients with
      colorectal cancer. A small proportion of these patients (10%) may be treated by
      surgical resection with five year survival approaching 35-40%. Alternative
      treatment modalities for localised hepatic disease include in situ ablative
      techniques that have the advantages of percutaneous application and minimal
      morbidity. These include Interstitial Laser Thermotherapy (ILT), Radio Frequency
      Ablation, Percutaneous Microwave therapy, and Focussed Ultrasound Therapy. This
      article focuses specifically on the development and utilisation of ILT in the
      treatment of colorectal liver metastases. It provides a review of the
      pathophysiological factors involved, present status of clinical studies, and
      future directions. ILT is a safe technique for the treatment of colorectal liver
      metastases. It may be delivered by minimally invasive techniques to lesions
      considered unresectable by present criteria. Limitations include the extent and
      completeness of tumour necrosis achieved as well as imaging techniques. Clinical
      problems include a lack of controlled studies. Assessment of long-term survival
      in prospective randomised trials is needed to assess the efficacy of this
      procedure.

PMID- 11223831
TI  - Correlation of MTS1/p16 and nm23 mRNA expression with survival in patients with
      peripheral synovial sarcoma.
AB  - BACKGROUND AND OBJECTIVES: Tumor suppressor gene MTS1/p16 (cyclin-dependent
      kinase-4 inhibitor) and a putative tumor metastasis suppressor gene nm23
      (nucleoside diphosphate A kinase) have been identified in a variety of human
      tumors but have not been well studied in mesenchymal neoplasms. METHODS:
      Expression of nm23 and MTS1 mRNA was determined by quantitative analysis from
      paraffin-embedded tumor tissue. The series comprised 31 patients with localized
      primary synovial sarcoma of soft tissues who were followed for a median of 83
      months. RESULTS: Neither MTS1 nor nm23 expression levels correlated with the
      patient's age or sex, tumor type, depth, size, mitotic rate, or extent of tumor
      necrosis. In addition, there was no correlation between MTS1 and nm23 levels.
      Patients' survival was not related to sex, age, tumor type, location, mitotic
      rate, or MTS1 mRNA level. The only factors that correlated with poor survival in
      multivariate analysis were the presence of extensive tumor necrosis (> 15%) and
      higher levels of nm23 mRNA. CONCLUSIONS: Our results suggest that increased
      expression level of nm23 mRNA may be implicated in the mechanism of tumor
      progression and is associated with poor survival in patients with synovial
      sarcoma.

PMID- 11223832
TI  - Splenectomy in proximal gastric cancer: frequency of lymph node metastasis to the
      splenic hilus.
AB  - BACKGROUND AND OBJECTIVES: The indication for splenectomy in proximal gastric
      cancer remains controversial. Splenectomy is performed because of possible lymph
      node metastasis of the splenic hilus or infiltration/metastasis of the spleen.
      The purpose of this study was to investigate the frequency of lymph node
      metastasis to the splenic hilus and metastasis to the spleen in proximal gastric
      carcinomas. METHODS: In a morphologic study, the frequency of lymph node
      metastasis to the splenic hilus in 112 patients with proximal gastric cancer was
      investigated with particular emphasis on its correlation with established
      clinicopathological characteristics and classifications. Seventy-seven
      gastrectomy specimens were obtained from men and 35 from women. Patients ranged
      in age from 20 to 89 years (median 60 years). All patients underwent a potential
      curative resection (RO resection) with total gastrectomy and pancreas-preserving
      splenectomy. None of the patients had been treated preoperatively with cytotoxic
      drugs or radiation. RESULTS: A mean number of three lymph nodes (range 0-8) in
      the splenic hilus was found in each specimen. The incidence of lymph node
      metastasis of the splenic hilus was 9.8% (n=11). Lymph node metastasis was only
      observed in advanced proximal gastric cancer (UICC IIIb/IV) located at the
      greater curvature and in Borrmann type III/IV cancer with advanced lymph node
      metastasis. An infiltration of the spleen was seen only in two cases with
      advanced stages of gastric carcinoma (stage IV). CONCLUSIONS: Based on our data
      lymph node metastasis to the splenic hilus is rarely observed in proximal gastric
      cancer and only found in advanced cancer (UICC IIIb/IV) especially in tumors of
      the greater curvature and of Borrmann type IV cancer.

PMID- 11223833
TI  - Commentary: frequency of lymph node metastases to the splenic hilum.

PMID- 11223834
TI  - Combination technique is superior to dye alone in identification of the sentinel
      node in breast cancer patients.
AB  - BACKGROUND: The purpose of the present study was to evaluate whether the
      combination of dye and radioisotope would improve the detection rate of sentinel
      nodes (SN) and the diagnostic accuracy of axillary lymph node status over dye
      alone in patients with breast cancer. METHODS: Sentinel node biopsy (SNB) was
      performed in stages I or II breast cancer patients with clinically negative nodes
      using dye alone (indocyanine green) or a combination of dye and radioisotope
      (99mTc-radiolabelled tin colloid). RESULTS: SNB guided by dye alone was performed
      in 93 patients and SNB guided by a combination of dye and radioisotope was
      performed in 138 patients. The detection rate of SN was significantly (P = 0.006)
      higher in the combination group (94.9%) than in the dye alone group (83.9%). The
      sensitivity, specificity, and overall accuracy of SNB in the diagnosis of
      axillary lymph node status were 100, 100, and 100%, respectively, for the
      combination group, and 81.0, 100, and 94.9%, respectively, for the dye alone
      group. There were no false negatives in the combination group, but four false
      negatives (19.0%) in the dye alone group. The combination method was
      significantly superior to the dye alone method for sensitivity (P = 0.011) and
      accuracy (P = 0.018). CONCLUSIONS: The addition of a radioisotope to the dye in
      SNB increases the detection rate of SNs in breast cancer patients, and SNs
      detected by the combination method predict the axillary lymph node status with
      greater accuracy than those detected by the dye alone method.

PMID- 11223835
TI  - Statistical analysis of diagnostic failure of fine needle aspiration cytology
      (FNAC) in breast cancer.
AB  - Fine-needle aspiration cytology (FNAC) was performed on 300 patients. Among
      those, 57 cases failed in accurate diagnosis of malignancy and 243 were
      successful. Fourteen clinicopathological factors altogether were analyzed to
      elucidate any correlation with FNAC failure using uni- and multivariate analysis.
      The univariate analysis in each clinicopathlogical factor showed that these error
      cases were vaguely palpable cancers, estrogen receptor (ER) positive cancers,
      small-sized of tumors, scattered type of cancer cell distribution in tumor
      tissues, with low tumor grade, with low Nottingham prognostic index (NPI), with
      benign-like ultrasound findings and with low TNM stage. The multivariate analysis
      revealed tumor grade was the strongest factor for all, followed by cellular
      distribution type of cancer cells and benign-like ultrasound findings. From these
      results, we speculated that diagnostic failure of FNAC at first clinic visit
      seemed to be caused by mainly two histocytological factors: extrinsic factor
      (structural factors of tissue-like tumor cells' distribution pattern, etc.); and
      intrinsic one (cellular factors of low atypism such as benign-like ultrasound
      finding, low tumor grade, and so on).

PMID- 11223836
TI  - Pharmacokinetics of intraperitoneal oxaliplatin: experimental studies.
AB  - BACKGROUND AND OBJECTIVES: Oxaliplatin is an antineoplastic platinum-based
      compound which has shown significant activity against advanced colon cancer. For
      cancers occurring within the abdominal cavity, the advantage of intraperitoneal
      chemotherapy is the high drug concentration that can be achieved locally with low
      systemic toxicity. Using a rat model, this study was designed to compare the
      pharmacokinetics and tissue absorption of intraperitoneal versus intravenous
      oxaliplatin. METHODS: In the first phase of this study, fifteen Sprague Dawley
      rats were given a single dose of oxaliplatin then randomized into three groups
      according to dose and route of delivery (5 mg/kg intravenously, 5 mg/kg
      intraperitoneally, or 25 mg/kg intraperitoneally). In the second phase, 10
      Sprague Dawley rats were given a continuous intraperitoneal perfusion of
      oxaliplatin (15 mg/kg) and randomized into two groups according to the
      temperature of the peritoneal perfusate (normothermic vs. hyperthermic). In both
      phases, peritoneal fluid and blood were sampled using a standardized protocol. At
      the end of each procedure the animals were sacrificed. Selected tissue samples
      were taken in the second phase only. For all samples, platinum levels were
      measured by direct current (d-c) plasma emission spectroscopy. RESULTS: When
      oxaliplatin was delivered at 5 mg/kg the area under the curve (AUC) of the
      peritoneal fluid was 15-fold higher with intraperitoneal administration as
      compared to intravenous administration (P < 0.0001). The AUC ratio (AUC
      peritoneal fluid/AUC plasma) was 16 (+/- 5):1 for intraperitoneal delivery as
      opposed to 1:5 (+/- 2) for intravenous delivery (P = 0.0059). The AUC ratio for
      intraperitoneal oxaliplatin at 25 mg/kg was 17 (+/- 8):1. With the exception of
      the kidneys and the mesenteric nodes, tissue samples in the hyperthermic group
      exhibited increased oxaliplatin concentrations. These differences were not
      significant. For both groups colon tissues had the highest oxaliplatin
      concentrations. CONCLUSIONS: These experiments demonstrated that the exposure of
      peritoneal surfaces to oxaliplatin was significantly increased with
      intraperitoneal administration. Although the differences were not statistically
      significant, hyperthermia did show a trend toward the enhancement of tissue
      absorption of oxaliplatin. The high concentration of drug observed in colonic
      tissues suggests the need for clinical studies to evaluate intraperitoneal
      oxaliplatin for microscopic residual tumor after surgical resection of colon
      malignancies.

PMID- 11223837
TI  - Expression of CD44 isoforms in squamous cell carcinoma of the border of the
      tongue: A correlation with histological grade, pattern of stromal invasion, and
      cell differentiation.
AB  - BACKGROUND AND OBJECTIVES: Oral squamous cell carcinoma is a frequent disease
      with reserved prognosis, where the routinely evaluated morphological features
      lack a major correlation with prognosis. In order to assess the potential value
      of the immunoexpression of CD44 isoforms v3, v4-5, and v6, we studied it in a
      series of 56 consecutive cases of squamous cell carcinomas of the border of the
      tongue. METHODS: All the histological (World Health Organization grade, Bryne
      score, degree of keratinization, and pattern of stromal invasion) and
      immunohistochemistry (using monoclonal antibodies to CD44v) results were
      exclusively assessed at the deep invasion front of the neoplasms. Downregulation
      of CD44v was defined by focal or irregular staining of < 10% of the cells at the
      deep invasive front. RESULTS: There was downregulation of CD44v3 in 37.5% of the
      cases, CD44v4-5 in 67.9%, and CD44v6 in 33.9%, occurring mostly in cases with low
      Bryne scores and graded as well-differentiated according to the WHO
      classification. Downregulation of CD44v was found to correlate with cell
      differentiation, tumor grade, and the pattern of neoplastic invasion.
      CONCLUSIONS: Our findings in the present series point to the consideration that
      CD44v pattern and intensity of immunoexpression in the deep invasive front of
      squamous cell carcinoma of the tongue are mostly related to tumor grade, the
      features of stromal invasion, and to the presence of cervical lymph node
      metastases.

PMID- 11223839
TI  - Repeat hepatectomy for colorectal liver metastases: A worthwhile operation?
AB  - BACKGROUND AND OBJECTIVES: After curative resection of hepatic colorectal
      metastases, 10-20% of patients experience a resectable hepatic recurrence. We
      wanted to assess the expected risk-to-benefit ratio in comparison to first
      hepatectomy and to determine the prognostic factors associated with survival.
      METHODS: Twenty-nine patients from a group of 152 patients resected for
      colorectal liver metastases underwent 32 repeat hepatectomies. RESULTS: In
      hospital mortality was 3.5% (1/29 patients); the morbidity after repeat
      hepatectomy was lower than that after first hepatic resection. Combined
      extrahepatic surgery was performed on 34.5% of repeat hepatectomies vs. 6.9% of
      first hepatectomies (P = 0.01). Overall actuarial 3-year survival was 35.1%: four
      patients have survived more than 3 years and one survived for more than 5 years.
      The number of hepatic metastases and the carcinoembryonic antigen (CEA) serum
      levels were significant prognostic factors on univariate analysis. The
      synchronous resection of hepatic and extrahepatic disease was not associated with
      a lower survival rate when compared with that of patients without extrahepatic
      localization: three patients of the former group are alive and disease-free at
      more than 2 years. CONCLUSIONS: Repeat hepatic resection can provide long-term
      survival rates similar to those of first liver resection, with comparable
      mortality and morbidity. The presence of resectable extrahepatic disease must not
      be an absolute contraindication to synchronous hepatectomy because long-term
      survival is possible.

PMID- 11223838
TI  - Infrequent microsatellite instability in biliary tract cancer.
AB  - BACKGROUND AND OBJECTIVES: Microsatellite instability (MSI) has been reported in
      several tumors. However, few reports are available concerning MSI in biliary
      tract cancers. We investigated MSI and allelic loss at the hMLH1 and hMSH2 gene
      loci in biliary tract cancers. METHODS: We analyzed microsatellite alterations
      using 7 microsatellite markers in 38 cases of extrahepatic bile duct (EHBD)
      cancer and 16 cases of ampullary cancer using polymerase chain reaction and an
      automated fluorescent DNA sequencer. RESULTS: A MSI prevalence of 13.2% (5/38)
      was observed for EHBD cancer and a prevalence of 12.5% (2/16) was observed for
      ampullary cancer. Loss of heterozygosity at the hMLH1 and hMSH2 gene loci were
      observed in 4% (1/25 informative cases) and 6.1% (2/33) of EHBD cancer cases,
      respectively; and in 11.1% (1/9) and 8.3% (1/12) of ampullary cancer cases,
      respectively. The cumulative survival rate of patients with MSI was significantly
      better than that of patients without MSI in EHBD cancer. However, MSI was not an
      independent prognostic factor. CONCLUSIONS: Our results suggest that genetic
      defects in the DNA mismatch repair system and MSI do not play an important role
      in the majority of biliary tract cancers.

PMID- 11223840
TI  - Prognostic value of the colposcopic tumor size in stage IB squamous cervical
      cancer.
AB  - BACKGROUND AND OBJECTIVES: To determine the prognostic significance of the
      colposcopic tumor size in the management of cervical cancer. METHODS:
      Clinicopathological analysis was performed in 751 consecutive patients with stage
      IB squamous cervical cancer who were surgically treated in a single institute.
      The colposcopic tumor size was measured postoperatively on surgical specimens.
      Univariate and multivariate analyses were performed to determine the prognostic
      significance of various pathological factors. RESULTS: Among the pathological
      factors examined, lymph node metastasis, parametrial extension, deep stromal
      invasion, vessel permeation, endometrial extension, and colposcopic tumor size
      were found to be prognostic factors in univariate analysis, whereas multivariate
      analysis has confirmed that only three factors, i.e., lymph node metastasis,
      parametrial involvement, and colposcopic tumor size were independently associated
      with the disease-free interval. CONCLUSIONS: These results indicate that the
      colposcopic tumor size is an independent prognostic factor in squamous cervical
      cancer and can be used as an indicator of treatment options.

PMID- 11223841
TI  - Safe pancreaticojejunostomy after Whipple procedure: modified technique.

PMID- 11223842
TI  - Simple technique of early identification of the thoracodorsal nerve during
      axillary dissection.

PMID- 11223844
TI  - Sentinel lymph node biopsy as an alternative to routine axillary lymph node
      dissection in breast cancer patients.
AB  - Sentinel lymph node (SLN) biopsy is a useful way of assessing axillary nodal
      status and obviating axillary lymph node dissection (ALND) in patients with node
      negative breast cancer. Because SLN technology is evolving rapidly, however,
      variation in technique is widespread, and no standardization has yet been
      accomplished. This review discusses the feasibility and accuracy of this
      procedure and suggests the optimal method for identifying the SLN and detecting
      micrometastases. Although the SLN can be successfully identified by either the
      dye-guided or gamma probe-guided method in experienced hands, identification is
      facilitated when the two techniques are used together. In the gamma probe-guided
      method, the use of a large-sized radiotracer (particle size, 200-1000 nm) may be
      preferred because only one or two SLNs are identified. To increase the chance of
      finding metastases in SLN, it is desirable to make step sections with hematoxylin
      and eosin staining on permanent and frozen sections. The addition of
      immunohistochemistry may improve the accuracy of SLN diagnosis. The
      intraoperative examination of imprint cytology may be useful in determining the
      status of the SLNs, but further studies are needed to establish whether it has
      additional value when combined with the frozen section. In practice, routine ALND
      can be avoided when there is documentation of extensive experience and a low
      false-negative rate with the technique in the hands of a particular surgeon and
      hospital team. Particularly, SLN biopsy is more successful and has a lower false
      negative rate in patients with smaller tumors. However, investigation of long
      term regional control and survival in a prospective randomized trial is
      necessary, before SLN biopsy can replace routine ALND as the preferred staging
      operation for women with breast cancer.

PMID- 11223845
TI  - Osteogenesis imperfecta and other skeletal dysplasias presenting with increased
      nuchal translucency in the first trimester.
AB  - We present two case reports of osteogenesis imperfecta associated with increased
      nuchal translucency in the first trimester. We also review the literature of
      first trimester diagnosis of skeletal dysplasias and their association with
      increased nuchal translucency.

PMID- 11223846
TI  - 46,XX gonadal dysgenesis, short stature, and recurrent metabolic acidosis in two
      sisters.
AB  - Gonadal (ovarian) dysgenesis in 46,XX individuals is genetically heterogeneous.
      We report on two sisters who, in addition to primary ovarian failure, have marked
      short stature and recurrent episodes of dehydration with metabolic acidosis.
      Studies performed during one of these episodes suggested mitochondrial
      dysfunction; however, results of biochemical analysis of electron transport chain
      activity in skeletal muscle and mitochondrial DNA studies were normal. We discuss
      the phenotype in relation to previously described conditions of 46,XX gonadal
      dysgenesis. We suggest this constellation of findings represents a new syndrome.

PMID- 11223847
TI  - No evidence of mutations in the follicle-stimulating hormone receptor gene in
      Mexican women with 46,XX pure gonadal dysgenesis.
AB  - In the ovary FSH is necessary for normal follicular development, binding to its
      receptor (FSHR) that pertains to the superfamily of G-protein coupled receptors.
      In the FSHR gene, which consists of 10 exons, an homozygous mutation was reported
      in six Finnish families with gonadal dysgenesis; whereas two isolated French
      patients exhibited compound heterozygous mutations. Several groups, however, have
      searched for FSHR mutations, although in most cases the gene has been studied
      partially, not finding any genetic abnormalities in German, English, North
      American or Brazilian women. We performed direct sequencing of all 10 exons of
      the FSHR gene in seven sporadic patients and two sisters with 46,XX pure gonadal
      dysgenesis, to investigate the cause of their disorder. No heterozygous or
      homozygous mutant alleles were present in any of the patients. Although the
      number of patients evaluated was small, considering all the other previous
      reports, it seems that except in the Finnish population, the proportion of women
      with mutations in the encoding region of this gene is very low. Other
      possibilities for the presence of 46,XX gonadal dysgenesis, such as defects in
      the regulatory regions of the FSHR gene promoter, in the untranslated regions of
      exons 1 and 10, and within introns, or the existence of other genes likely to be
      important for normal ovarian function on the X chromosome or on autosomes, should
      be considered. In contrast with other studies, we did not find polymorphisms of
      the FSHR gene, indicating that apparently in Mexicans this gene is not highly
      polymorphic.

PMID- 11223848
TI  - Role for anti-Mullerian hormone in congenital absence of the uterus and vagina.
AB  - Molecular genetic techniques were used to determine if mutations in the genes
      encoding anti-Mullerian hormone (AMH) (also known as Mullerian inhibiting
      substance (MIS)) and its receptor (AMHR) are commonly present in patients with
      congenital absence of the uterus and vagina (CAUV). Twenty-two CAUV patients and
      96 control subjects from diverse ethnic groups were studied after obtaining
      informed consent. Genomic DNA samples prepared from leukocytes were digested
      separately with several different restriction enzymes, and the resultant
      fragments were analyzed for restriction fragment melting polymorphisms (RFMPs) by
      denaturing gradient gel electrophoresis (DGGE). Electrophoretic mobility of DNA
      fragments which were 200-700 base pairs in length was compared using
      polyacrylamide gels that included linear gradients of denaturing solvents
      designed to separate DNA fragments according to sequence-dependent variation in
      thermal stability. Two RFMPs were found in the AMH gene in both patients and
      normal control subjects. One RFMP in the AMHR gene was present at low frequencies
      in both patients and normal control subjects. No RFMPs specific to CAUV patients
      were found in either gene. Because no mutations or rare DNA sequence
      polymorphisms were detected in the AMH and the AMHR genes in this group of CAUV
      patients, it is unlikely that either gene commonly has an etiologic role in CAUV.

PMID- 11223849
TI  - Distal 13q Deletion Syndrome and the VACTERL association: case report, literature
      review, and possible implications.
AB  - We present a case of a child with del(13) (q31.1qter), VACTERL association, and
      penoscrotal transposition. Deletion of the distal long arm of chromosome 13 is
      associated with variable phenotypes. These phenotypes are divided into three
      clusters; each cluster represents a specific deleted segment of 13q. Individuals
      with deletions of a critical region at 13q32 have multiple congenital
      malformations that include components of the VACTERL association. Our patient had
      all six manifestations of VACTERL association. In addition, he had complete
      penoscrotal transposition, a unique malformation reported rarely in VACTERL
      association and only twice previously in deletion of distal 13q. We reviewed all
      reported cases of distal 13q deletions to date. Of these 137 patients, 15 could
      be classified into the VACTERL association. Ours was the only patient with distal
      13q deletion and all VACTERL association features and also the only one with
      tracheoesophageal fistula. Neither holoprosencephaly nor the other central
      nervous system malformations that have been seen in individuals with distal 13q
      deletions were apparent in him. The patient presented here appears to be unique
      among individuals with distal 13q deletion. His cluster of malformations
      strengthens the argument that distal 13q deletion is a cause for VACTERL
      association, and that this causal relationship implies a syndromic form of
      VACTERL. In addition, this case and those ascertained from the literature suggest
      that penoscrotal transposition should be considered part of both the distal 13q
      deletion syndrome and some forms of VACTERL association.

PMID- 11223850
TI  - Phylloid pattern of pigmentary disturbance in a case of complex mosaicism.
AB  - Among the various types of pigmentary disturbances associated with mosaicism, the
      phylloid pattern (Greek phyllon = leaf, eidos = form) is characterized by
      multiple leaf-like patches reminiscent of an art nouveau painting. The number of
      cases displaying this unusual pattern is so far limited. We describe a phylloid
      pattern of hypomelanosis in a 3-year-old girl with multiple congenital anomalies
      including microcephaly, midfacial hypoplasia, cleft lip, coloboma, posteriorly
      rotated ears, pectus carinatum, and pronounced mental and physical retardation.
      In addition, this child had oval or oblong patches of hyperpigmentation involving
      the trunk in a horizontal arrangement dissimilar from the phylloid hypomelanotic
      pattern. In peripheral blood lymphocytes a karyotype 46,XX,-13,+t(13q;13q) was
      consistently found, whereas cultured skin fibroblasts showed a complex form of
      mosaicism comprising three different abnormal cell lines (46,XX,
      13,+t(13q;13q)/45,XX,-13/45,XX,-13,+frag). This case provides further evidence
      that the phylloid pattern represents a separate category of pigmentary
      disturbance to be distinguished from other types of cutaneous mosaicism such as
      the lines of Blaschko or the checkerboard arrangement.

PMID- 11223851
TI  - Efficient detection of Alport syndrome COL4A5 mutations with multiplex genomic
      PCR-SSCP.
AB  - We have performed effective mutation screening of COL4A5 with a new method of
      direct, multiplex genomic amplification that employs a single buffer condition
      and PCR profile. Application of the method to a consecutive series of 46 United
      States patients with diverse indications of Alport syndrome resulted in detection
      of mutations in 31 cases and of five previously unreported polymorphisms. With a
      correction for the presence of cases that are not likely to be due to changes at
      the COL4A5 locus, the mutation detection sensitivity is greater than 79%. The
      test examines 52 segments, including the COL4A6/COL4A5 intergenic promoter
      region, all 51 of the previously recognized exons and two newly detected exons
      between exons 41 and 42 that encode an alternatively spliced mRNA segment. New
      genomic sequence information was generated and used to design primer pairs that
      span substantial intron sequences on each side of all 53 exons. For SSCP
      screening, 16 multiplex PCR combinations (15 4-plex and 1 3-plex) were used to
      provide complete, partially redundant coverage of the gene. The selected
      combinations allow clear resolution of products from each segment using various
      SSCP gel formulations. One of the 29 different mutations detected initially
      seemed to be a missense change in exon 32 but was found to cause exon skipping.
      Another missense variant may mark a novel functional site located in the
      collagenous domain.

PMID- 11223852
TI  - Abnormal dendritic spine characteristics in the temporal and visual cortices of
      patients with fragile-X syndrome: a quantitative examination.
AB  - Fragile-X syndrome is a common form of mental retardation resulting from the
      inability to produce the fragile-X mental retardation protein. Qualitative
      examination of human brain autopsy material has shown that fragile-X patients
      exhibit abnormal dendritic spine lengths and shapes on parieto-occipital
      neocortical pyramidal cells. Similar quantitative results have been obtained in
      fragile-X knockout mice, that have been engineered to lack the fragile-X mental
      retardation protein. Dendritic spines on layer V pyramidal cells of human
      temporal and visual cortices stained using the Golgi-Kopsch method were
      investigated. Quantitative analysis of dendritic spine length, morphology, and
      number was carried out on patients with fragile-X syndrome and normal age-matched
      controls. Fragile-X patients exhibited significantly more long dendritic spines
      and fewer short dendritic spines than did control subjects in both temporal and
      visual cortical areas. Similarly, fragile-X patients exhibited significantly more
      dendritic spines with an immature morphology and fewer with a more mature type
      morphology in both cortical areas. In addition, fragile-X patients had a higher
      density of dendritic spines than did controls on distal segments of apical and
      basilar dendrites in both cortical areas. Long dendritic spines with immature
      morphologies and elevated spine numbers are characteristic of early development
      or a lack of sensory experience. The fact that these characteristics are found in
      fragile-X patients throughout multiple cortical areas may suggest a global
      failure of normal dendritic spine maturation and or pruning during development
      that persists throughout adulthood.

PMID- 11223853
TI  - Valproic acid embryopathy: report of two siblings with further expansion of the
      phenotypic abnormalities and a review of the literature.
AB  - Fetal Valproate Syndrome (FVS) results from prenatal exposure to valproic acid
      (VPA). It is characterized by a distinctive facial appearance, a cluster of minor
      and major anomalies, and central nervous system dysfunction. In this study, two
      siblings who were exposed to monotherapy with VPA are described with
      documentation of long-term follow up. Both children had craniofacial findings,
      multiple systemic and orthopedic abnormalities, an overgrowth pattern, and
      developmental deficits. The literature from 1978-2000 is reviewed. A total of 69
      cases that were solely exposed to VPA with adequate phenotypic description were
      identified. The clinical manifestations of FVS encompass a wide spectrum of
      abnormalities including consistent facial phenotype, multiple systemic and
      orthopedic involvement, central nervous system dysfunction, and altered physical
      growth. The facial appearance is characterized by a small broad nose, small ears,
      flat philtrum, a long upper lip with shallow philtrum, and micro/retrognathia. In
      this review, 62% of the patients had musculoskeletal abnormalities, 30% had minor
      skin defects, 26% had cardiovascular abnormalities, 22% had genital
      abnormalities, and 16% had pulmonary abnormalities. Less frequently encountered
      abnormalities included brain, eye, kidney, and hearing defects. Neural tube
      defects were seen in 3% of the sample. Twelve percent of affected children died
      in infancy and 29% of surviving patients had developmental deficits/mental
      retardation. Although 15% of patients had growth retardation, an overgrowth
      pattern was seen in 9%. The data from this comprehensive review especially the
      developmental outcome should be added to the teratogenic risk, that arises in
      association with the use of VPA during pregnancy.

PMID- 11223854
TI  - Genetic study of SOX9 in a case of campomelic dysplasia.
AB  - Campomelic dysplasia (CD) is a sporadic autosomal dominant syndrome that results
      in skeletal malformation and developmental abnormalities. Death usually occurs
      neonatally as a result of respiratory insufficiencies, but life expectancy varies
      depending on the severity of the phenotype. XY sex reversal is common in CD, and
      a range of genital defects is observed in males and females. CD is due to
      mutations in SOX9, a member of the SOX (SRY-related HMG box) gene family. SOX9 is
      a transcription factor involved in chondrogenesis and sex determination. We
      present a CD patient with a normal 46,XX karyotype and female phenotype. Single
      stranded conformation polymorphism analysis of DNA from this CD patient
      demonstrated a single-stranded conformation polymorphism shift in the C-terminal
      region of SOX9. DNA sequencing showed a frameshift mutation resulting from the
      insertion of a single guanine residue in nucleotide region 1,453-1,456. This
      insertion mutation creates a mutant SOX9 open reading frame that is 201
      nucleotides longer than the normal gene. It has been shown that the C-terminal
      region of SOX9 is responsible for the transactivating ability of the protein. The
      frameshift identified here affects approximately half of the protein region
      needed for full transactivating function. We hypothesize that residual SOX9
      function may explain why this patient survived infancy.

PMID- 11223855
TI  - An 11-year-old boy with mosaic ring chromosome 6 and dilated aortic root.
AB  - Autosomal ring chromosomes are rare abnormalities that are inherently unstable.
      Children with ring chromosome 6 have a wide range of intellectual functioning and
      congenital anomalies. Cardiac lesions are rarely reported with this chromosome
      abnormality. We report on a 11-year-old boy with mosaic ring chromosome 6 and a
      dilated aortic root.

PMID- 11223856
TI  - Craniofacial and dental characteristics of Kabuki syndrome.
AB  - We describe oral manifestations in six patients (three females and three males
      aged 6 to 24 years) with Kabuki syndrome (KS), based on their physical,
      orthopantomographic, and cephalometric findings. All six patients had a high
      arched palate, malocclusion, most commonly unilateral posterior cross-bite (5/6),
      severe maxillary recession and mid-facial hypoplasia. Other frequently observed
      oral manifestations included small dental arch and hypodontia. Three patients
      lacked permanent teeth, mostly the central/lateral incisors. Both tooth size (in
      primary and permanent teeth) and dental arch (in length and width) tended to be
      small. We would like to stress that oral care and management is a must for the
      well-being of KS patients.

PMID- 11223857
TI  - Behavior phenotype in the RSH/Smith-Lemli-Opitz syndrome.
AB  - The behavior phenotype of Smith-Lemli-Opitz syndrome (SLOS) was studied by
      assessing behavior, social, and communication abilities, sensory hyperreactivity,
      and the deficits associated with autistic disorder. Fifty-six SLOS subjects, age
      0.3 to 32.3 years, were evaluated by multiple age-dependent questionnaires and
      telephone interviews. Of the 56 subjects, 50 (89%) had a history of repeated self
      injury: 30 (54%) bit themselves; 27 (48%) head-banged; and 30 (54%) threw
      themselves backward in a highly characteristic upper body movement
      ("opisthokinesis"). Forty-seven of these subjects were also evaluated by direct
      observation and by direct interview of the parent or caregiver. Of 11 subjects 10
      years or older, three (27%) had a stereotypic stretching motion of the upper body
      accompanied by hand flicking. Additional measures showed sensory hyperreactivity,
      temperament dysregulation, sleep disturbance, and social and communication
      deficits. Nine of 17 subjects (53%) met the diagnostic criteria for autistic
      disorder by the Autism Diagnostic Interview-Revised (ADI-R) algorithm questions
      [Lord et al., 1993, 1994]. Thus, SLOS is a metabolic disorder that can be
      associated with autism and other behavioral characteristics that define a
      distinctive and diagnostically important behavioral disorder.

PMID- 11223858
TI  - High maternal fever during gestation and severe congenital limb disruptions.
AB  - Hyperthermia is defined as a temperature of at least 1.5 degrees C over the
      normal core body temperature. It is a proven teratogen in animals and in humans.
      The type of defects induced by hyperthermia in experimental animals are:
      anencephaly/exencephaly, encephalocele, microphthalmia, arthrogryposis, abdominal
      wall defects, limb deficiencies, embryonic death, and resorption. In humans it
      has been observed that infants prenatally exposed to hyperthermia presented with
      spina bifida, encephalocele, microphthalmia, micrognathia, external ear
      anomalies, cardiac defects, hypospadias, gastrointestinal defects, cleft lip
      and/or cleft palate, abdominal wall defects, diaphragmatic hernia, Hirschsprung
      disease, Mobius syndrome, oromandibular-limb hypogenesis spectrum, and
      spontaneous abortions. We describe an additional case with severe limb
      deficiencies whose mother had fever over 39 degrees C for 2 days in the second
      and in the fourth month of amenorrhoea. We conclude that, based on the degree of
      development of the humeri and the femora and the type of limb deficiencies, this
      case presents a disruption that most probably occurred in the fourth month of
      gestation.

PMID- 11223859
TI  - Folic acid and miscarriage: an unjustified link.

PMID- 11223861
TI  - Adenosine deaminase: functional implications and different classes of inhibitors.
AB  - Adenosine deaminase (ADA) is an enzyme of the purine metabolism which catalyzes
      the irreversible deamination of adenosine and deoxyadenosine to inosine and
      deoxyinosine, respectively. This ubiquitous enzyme has been found in a wide
      variety of microorganisms, plants, and invertebrates. In addition, it is present
      in all mammalian cells that play a central role in the differentiation and
      maturation of the lymphoid system. However, despite a number of studies performed
      to date, the physiological role played by ADA in the different tissues is not
      clear. Inherited ADA deficiency causes severe combined immunodeficiency disease
      (ADA-SCID), in which both B-cell and T-cell development is impaired. ADA-SCID has
      been the first disorder to be treated by gene therapy, using polyethylene glycol
      modified bovine ADA (PEG-ADA). Conversely, there are several diseases in which
      the level of ADA is above normal. A number of ADA inhibitors have been designed
      and synthesized, classified as ground-state and transition-state inhibitors. They
      may be used to mimic the genetic deficiency of the enzyme, in lymphoproliferative
      disorders or immunosuppressive therapy (i.e., in graft rejection), to potentiate
      the effect of antileukemic or antiviral nucleosides, and, together with adenosine
      kinase, to reduce breakdown of adenosine in inflammation, hypertension, and
      ischemic injury.

PMID- 11223863
TI  - The role and regulation of urokinase-type plasminogen activator receptor gene
      expression in cancer invasion and metastasis.
AB  - This article reviews the role of urokinase-type plasminogen activator receptor
      (uPAR) and its protein, mRNA, cDNA, genomic organization, promoter, transcription
      activation factors, and signal transduction. The uPAR has been implicated in
      several biological processes including angiogenesis, monocyte migration, cancer
      metastasis, trophoblast implantation, and wound healing. It is a specific cell
      surface receptor for its ligand uPA which catalyzes the formation of plasmin from
      plasminogen to generate the proteolytic cascade that contributes to the breakdown
      of extracellular matrix, a key step in cancer metastasis. The uPAR is a 55-60 kDa
      glycoprotein organized as three homologous cysteine-rich domains. It attaches to
      the plasma membrane via a covalent linkage to a glycosyl-phosphatidylinositol
      (GPI) moiety and appears to play an important role in transmembrane signalling.
      The 1.4-kb human uPAR cDNA and 21.23-kb genomic DNA have been cloned and the gene
      contains seven exons. The uPAR promoter region was defined in a 188 bp fragment
      between bases -141 and +47 relative to the transcription start site. Binding of
      transcription factors (Sp1, AP-2, NFkappaB and two AP-1) to the uPAR promoter
      region activates the basal transcription of the gene. There is a strong
      correlation between uPAR expression and the invasive cancer cell phenotype. uPAR
      may play a critical role in the process of cancer invasion and metastasis, as
      antisense uPAR mRNA can inhibit cancer spread in vitro and in vivo. These studies
      may provide a novel therapeutic target for blocking cancer invasion and
      metastasis.

PMID- 11223862
TI  - Inhibition of p38 mitogen-activated protein kinase provides neuroprotection in
      cerebral focal ischemia.
AB  - Mitogen-activated protein kinases (MAPKs) are involved in many cellular
      processes. The stress-activated MAPK, p38, has been linked to inflammatory
      cytokine production and cell death following cellular stress. Here, we
      demonstrate focal ischemic stroke-induced p38 enzyme activation (i.e.,
      phosphorylation) in the brain. The second generation p38 MAPK inhibitor SB 239063
      was identified to exhibit increased kinase selectivity and improved cellular and
      in vivo activity profiles, and thus was selected for evaluation in two rat models
      of permanent focal ischemic stroke. SB 239063 was administered orally pre- and
      post-stroke and intravenously post-stroke. Plasma concentration levels were
      achieved in excess of those that effectively inhibit p38 activity. In both
      moderate and severe stroke, SB 239063 reduced infarct size by 28-41%, and
      neurological deficits by 25-35%. In addition, neuroprotective plasma
      concentrations of SB 239063 that reduced p38 activity following stroke also
      reduced the stroke-induced expression of IL-1beta and TNFalpha (i.e., cytokines
      known to contribute to stroke-induced brain injury). SB 239063 also provided
      direct protection of cultured brain tissue to in vitro ischemia. This robust SB
      239063-induced neuroprotection emphasizes a significant opportunity for targeting
      MAPK pathways in ischemic stroke injury, and also suggests that p38 inhibition be
      evaluated for protective effects in other experimental models of nervous system
      injury and neurodegeneration.

PMID- 11223864
TI  - Direct effects of estrogen on the vessel wall.
AB  - The understanding of the biological effects of estrogen on the vessel wall has
      improved dramatically since the discovery of estrogen receptors (ERs). Most, but
      not all estrogen-mediated effects in blood vessels are thought to be mediated by
      ERs. Two major ER subclasses have been characterized so far: the ERalpha and the
      more recently described ERbeta. This review will primarily focus on a new
      perspective that highlights ERs as essential mediators of the vascular effects of
      estrogen. In view of the rising research interest in this area, it can be also
      expected that tissue- and ER subclass-selective agonists and antagonists will be
      developed over the next few years, thus providing invaluable tools for
      pharmacological and clinical applications.

PMID- 11223865
TI  - Evidence for the involvement of polyunsaturated fatty acids in the regulation of
      long-chain acyl CoA thioesterases and peroxisome proliferation in rat
      carcinosarcoma.
AB  - The feeding of high-fat diets rich in polyunsaturated fatty acids (PUFAs) caused
      a marked increase in the acyl CoA thioesterase activity of the Walker 256 tumour.
      Diets containing lower levels of PUFAs did not alter the activity of acyl CoA
      thioesterase and the exposure of LLC-WRC256 tumour cells, in culture, to PUFAs
      (150 microM) also was ineffective in altering activity. The tumours from n-3 PUFA
      rich and control diets were analysed by transmission electron microscopy in order
      to compare peroxisomal content. The presence of PUFAs led to an almost 10-fold
      increase in the number of peroxisomes present in the tumour tissue. A common
      feature of the PUFA-treated tumour was the presence of many cells containing
      highly condensed heterochromatin at the periphery of the nucleus, indicative of
      apoptosis. The sparsity of endoplasmic reticulum and the lack of detection of
      mitochondrial acyl CoA thioesterase, MTE-I, led to the conclusion that the
      increase in tumour acyl CoA thioesterase activity may be due to an increase in
      the activity of the peroxisomal enzyme.

PMID- 11223866
TI  - Macrophages transfer [14C]-labelled fatty acids to pancreatic islets in culture.
AB  - Macrophages are able to produce, export, and transfer fatty acids to lymphocytes
      in culture. The purpose of this study was to examine if labelled fatty acids
      could be transferred from macrophages to pancreatic islets in co-culture. We
      found that after 3 h of co-culture the transfer of fatty acids to pancreatic
      islets was: arachidonic >> oleic > linoleic = palmitic. Substantial amounts of
      the transferred fatty acids were found in the phospholipid fraction; 87.6% for
      arachidonic, 59.9% for oleic, 53.1% for palmitic, and 36.9% for linoleic acids.
      The remaining radioactivity was distributed among the other lipid fractions
      analysed (namely polar lipids, cholesterol, fatty acids, triacylglycerol and
      cholesterol ester), varying with the fatty acid used. For linoleic acid, a
      significant proportion (63.1%) was almost equally distributed in these lipid
      fractions. Also, it was observed that transfer of fatty acids from macrophages to
      pancreatic islets is time-dependent up to 24 h, being constant and linear with
      time for palmitic acid and remaining constant after 12 h for oleic acid. These
      results lead us to postulate that in addition to the serum, circulating monocytes
      may also be a source of fatty acids to pancreatic islets, mainly arachidonic
      acid.

PMID- 11223867
TI  - Effects of polyamines on DNA synthesis using various subcellular DNA polymerases
      extracted from normal rat liver, tumour-bearing rat liver, and tumour cells.
AB  - The effects of polyamines on DNA synthesis in vitro using various subcellular DNA
      polymerase fractions from normal and tumour-bearing rat livers, and tumour cells
      were investigated. When nuclear and mitochondrial DNA polymerase fractions were
      used, DNA synthesis on activated DNA was increased 3.5-8-fold by the addition of
      20 mM putrescine or cadaverine. However, DNA synthesis was not stimulated by the
      addition of spermidine or spermine at any concentration tested. In contrast, DNA
      synthesis using the cytoplasmic DNA polymerase fraction was not stimulated at
      various concentrations of any of the four polyamines tested. The stimulatory
      effects of putrescine and cadaverine were absent when nuclear fractions from
      tumour-bearing rat liver or from tumour cells were used. In addition, in vitro
      DNA synthesis was not stimulated by 20 mM putrescine or cadaverine when nuclear
      extracts from the livers of rats administered putrescine subcutaneously were
      used. The specific activities of DNA polymerases extracted from tumour cells and
      tumour-bearing rat liver were already fully stimulated. These results suggest
      that DNA polymerases in tumour cells and tumour-bearing liver cells are
      stimulated by trapped putrescine produced in tumour cells and are thus no longer
      activated by exogenous putrescine.

PMID- 11223868
TI  - Effect of selenium on N-nitrosodiethylamine-induced multistage
      hepatocarcinogenesis with reference to lipid peroxidation and enzymic
      antioxidants.
AB  - We have studied the relationship between antioxidant and anticancer properties of
      selenium (Se) in multistage hepatocarcinogenesis induced by N-nitrosodiethylamine
      (DEN). In this study we have observed an increased level of lipid peroxide (LPO)
      products and decreased antioxidant enzyme activities (superoxide dismutase and
      catalase) in hepatoma and surrounding liver tissues of cancer-bearing animals.
      Selenium (Se) was supplemented either before initiation or during initiation and
      selection/promotion phases of hepatocarcinogenesis and was found to be effective
      in altering hepatic lipid peroxidation and antioxidant enzyme activities to a
      statistically significant level measured either in the hepatoma or in the
      surrounding liver tissues. These alterations inclined towards normal in a time
      dependent manner on selenium supplementation. Furthermore, increased levels of
      lipid peroxidation and decreased levels of antioxidants (superoxide dismutase and
      catalase) were also observed in distant organs of cancer-bearing rats other than
      the tumour-bearing site. These alterations are brought back to normal levels upon
      Se treatment. Our results confirm the fact that Se is particularly protective in
      limiting the action of DEN by its antioxidant property.

PMID- 11223869
TI  - Effect of melatonin on oxidative status of rat brain, liver and kidney tissues
      under constant light exposure.
AB  - An enormous amount of data has been published in recent years demonstrating
      melatonin's defensive role against toxic free radicals. In the present study, we
      examined the role of melatonin as an antioxidant against the effect of continuous
      light exposure. Rats were divided into three groups. Control rats (group A) were
      kept under natural conditions whereas other group of rats (group B and C) were
      exposed to constant light for inhibition of melatonin secretion by the pineal
      gland. Group C rats also received melatonin via s.c. injection (1 mg x kg(- 1)
      body weight x day(- 1)). At the end of experiment, all animals were sacrificied
      by decapitation, serum and tissue samples were removed for determination of
      malondialdehyde (MDA), a product of lipid peroxidation, conjugated dienes levels
      and glutathione peroxidase (GSH-Px) activity levels. It was found that lipid
      peroxidation was increased in the rats which were exposed to constant light.
      Melatonin injection caused a decrease in lipid peroxidation, especially in the
      brain. In addition, melatonin application resulted in increased GSH-Px activity,
      which has an antioxidant effect. Thus, melatonin is not only a direct scavenger
      of toxic radicals, but also stimulates the antioxidative enzyme GSH-Px activity
      to detoxify hydroxyl radical produced by constant light exposure.

PMID- 11223870
TI  - Roles of phosphatidylinositol 3-kinase and phospholipase D in temporal activation
      of superoxide production in FMLP-stimulated human neutrophils.
AB  - To determine the temporal roles of phosphatidylinositol 3-kinase (PI3-kinase) and
      phospholipase D (PLD) during human neutrophil activation stimulated by a
      chemotactic peptide, we examined the kinetics of these enzymes and related them
      to a neutrophil function (superoxide production). Both wortmannin and 2-(4
      morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), potent and specific
      inhibitors of PI3-kinase, inhibit PI3-kinase activity in human neutrophils and
      significantly inhibit superoxide production from the early phase. Ethanol has no
      effect on PI3-kinase and markedly inhibits superoxide production at the late
      phase. Although these agents are inhibitory to different degrees, when
      neutrophils are simultaneously treated with ethanol and PI3-kinase inhibitors,
      superoxide is not produced. These results suggest that PI3-kinase and PLD play a
      pivotal role in the signal transduction pathway of the chemo-attractant-receptor
      involved neutrophil activation. These enzymes produce second messengers which are
      required for subsequent superoxide production in human neutrophils. NADPH oxidase
      is activated in a PI3-kinase-dependent manner at the early phase, and PLD
      activity follows it and is related to superoxide production at the late phase in
      human neutrophils by stimulation with FMLP.

PMID- 11223871
TI  - Control of apolipoprotein E secretion in the human hepatoma cell line KYN-2.
AB  - Even though it is known that apolipoprotein E (apoE) is deeply involved in major
      age-related disorders such as atherosclerosis or Alzheimer's disease (AD), the
      control of cell-specific apoE expression is still poorly understood. We compared
      the apoE secretion as previously described in astrocytic cell17 to hepatic cell
      apoE secretion. We used the human hepatoma cell line KYN-2 to better delineate
      the characteristics of apoE secretion and to validate it with respect to the
      classical human hepatoma cell line HepG2. Interleukin-1beta (IL-1beta) and
      interferon-gamma (IFN-gamma) significantly inhibited, while IL-2, IL-6 and tumour
      necrosis factor-alpha (TNF-alpha) were inactive on apoE secretion by KYN-2 as
      well as HepG2 cells. Cholesterol and 25-OH cholesterol had no effect, while
      forskolin exerted a significant inhibitory effect, on apoE secretion in KYN-2
      cells. Our results suggest that the KYN-2 cell line represents an appropriate
      cell model, and in any case an alternative model to the HepG2 cell line, to study
      the control of apoE secretion. The response of KYN-2 cells to both cytokines and
      cholesterol differs from that found in astrocytoma cells, suggesting that blood
      variations of apoE concentrations in AD may not reflect the dysregulations taking
      place in the brain.

PMID- 11223872
TI  - Ultrastructural analysis of HNE-treated Saccharomyces cerevisiae cells reveals
      fragmentation of the vacuole and an accumulation of lipids in the cytosol.

PMID- 11223873
TI  - Telomerase activity is repressed during differentiation along the hepatocytic and
      biliary epithelial lineages: verification on immortal cell lines from the same
      origin.
AB  - Recent investigations indicate that telomerase activity regulates the life span
      of cells by compensating for telomere shortening during DNA replication. In
      addition, as differentiation progresses, telomerase activity is reduced in
      several different cell lineages. These findings lend support to the theory that
      more immature cells have greater remaining proliferative capacity and longer life
      span. However, it has not been directly demonstrated that the differentiation
      along a hepatocytic or a bile ductal lineage is accompanied by reduction of
      telomerase activity. In this study, we present direct evidence that telomerase
      activity is reduced during hepatocytic and biliary epithelial differentiation by
      using our unique cell lines including a stem-like cell line, ETK-1. When
      hepatocytic differentiation was induced in ETK-1 by 5-azacytidine, telomerase
      activity decreased significantly. Similarly, when we compared the telomerase
      activity on SSP-25 and RBE cell lines from the same origin but representing
      different maturation stages of cholangiocarcinoma, more mature cells were found
      to possess significantly lower activity. These results indicate that the
      generally accepted relationship between telomerase activity and differentiation
      stage also applies in the hepatocytic and biliary epithelial lineages.

PMID- 11223874
TI  - Increased serum angiotensin converting enzyme activity in diabetes mellitus is
      not a uniform finding.

PMID- 11223876
TI  - An arrow for wingless to take-off.
AB  - The Wnt family of secreted glycoproteins is involved in the regulation of diverse
      developmental processes. The classical Wnt/beta-catenin pathway has been
      thoroughly investigated resulting in the identification of a plethora of
      components involved in the activation of beta-catenin target genes. Moreover, two
      additional Wnt-triggered pathways have been identified. These various signalling
      cascades require at least one component that confers signalling specificity. This
      function is fulfilled at least in part by the Wnt receptor Frizzled. The recent
      identification of a potential Frizzled co-receptor, an LDL-receptor-related
      protein (LRP), sheds more light on Wnt-signal transduction specificity and
      promises more exciting revelations.

PMID- 11223877
TI  - Hox genes in a pentameral animal.
AB  - There is renewed interest in how the different body plans of extant phyla are
      related. This question has traditionally been addressed by comparisons between
      vertebrates and Drosophila. Fortunately, there is now increasing emphasis on
      animals representing other phyla. Pentamerally symmetric echinoderms are a
      bilaterian metazoan phylum whose members exhibit secondarily derived radial
      symmetry. Precisely how their radially symmetric body plan originated from a
      bilaterally symmetric ancestor is unknown, however, two recent papers address
      this subject. Peterson et al. propose a hypothesis on evolution of the
      anteroposterior axis in echinoderms, and Arenas-Mena et al. examine expression of
      five posterior Hox genes during development of the adult sea urchin.

PMID- 11223878
TI  - Spatial compartmentalization of signal transduction in insulin action.
AB  - Insulin resistance is thought to be the primary defect in the pathophysiology of
      type 2 diabetes. Thus, understanding the cellular mechanisms of insulin action
      may contribute significantly to developing new treatments for this disease.
      Although the effects of insulin on glucose and lipid metabolism are well
      documented, gaps remain in our understanding of the precise molecular mechanisms
      of signal transduction for the hormone. One potential clue to understanding the
      unique cellular effects of insulin may lie in the compartmentalization of
      signaling molecules and metabolic enzymes. We review this evidence, and speculate
      on how PI-3 kinase-independent and -dependent signaling pathways both diverge
      from the insulin receptor and converge at discrete targets to insure the
      specificity of insulin action.

PMID- 11223879
TI  - Structural insights on Smad function in TGFbeta signaling.
AB  - TGFbeta signaling plays a central role in regulating a broad range of cellular
      responses in a variety of organisms. TGFbeta signaling from the cell membrane to
      the nucleus is mediated by the Smad family of proteins. During the past five
      years of intense investigation, key events in TGFbeta signaling have been
      documented at the molecular and cellular level. Recent structural studies have
      improved our understanding of how specificity is generated in the TGFbeta
      signaling pathways. Despite this progress, significant questions remain regarding
      the precise mechanisms of signaling and point to the urgent need for well
      controlled biochemical studies. Rather than giving a comprehensive review on Smad
      mediated TGFbeta signaling, this review focuses on functional insights provided
      by recent structural studies and discusses several existing controversies.

PMID- 11223880
TI  - Frogs without polliwogs: evolution of anuran direct development.
AB  - Direct development is the assumption of the adult morphology without progression
      through an intervening, morphologically distinct, free-living larval phase. We
      discuss the ecological factors contributing to the evolution of this derived life
      history strategy in frogs, and the developmental modifications that facilitate
      such an unusual mode of embryogenesis. Studies on the Puerto Rican tree frog,
      Eleutherodactylus coqui, have identified several such modifications, including
      developmental adaptations for dealing with increased egg size, and loss of
      tadpole structures. Surprisingly, this direct developer still undergoes a thyroid
      hormone-dependent metamorphosis, which occurs before hatching. We suggest how the
      ancestral biphasic developmental pattern may have been rearranged during the
      evolution of direct development.

PMID- 11223881
TI  - Chromosome elimination in sciarid flies.
AB  - The programmed elimination of part of the genome through chromosome loss or
      chromatin diminution constitutes an exceptional biological process found to be
      present in several diverse groups of organisms. The occurrence of this phenomenon
      during early embryogenesis is generally correlated to somatic versus germ-line
      differentiation. A most outstanding example of chromosome elimination and genomic
      imprinting is found in sciarid flies, where whole chromosomes of exclusive
      parental origin are selectively eliminated at different developmental stages.
      Three types of tissue-specific chromosome elimination events occur in sciarids.
      During early cleavages, one or two X paternal chromosomes is/are discarded from
      somatic cells of embryos which then develop as females or males respectively.
      Thus, the sex of the embryo is determined by the number of eliminated paternal X
      chromosomes. In germ cells, instead, a single paternal X chromosome is eliminated
      in embryos of both sexes. In addition, while female meiosis is orthodox, male
      meiosis is highly unusual as the whole paternal chromosome set is discarded from
      spermatocytes. As a consequence, only maternally derived chromosomes are included
      in the functional sperm. This paper reviews current cytological and molecular
      knowledge on the tissue-specific cell mechanisms evolved to achieve chromosome
      elimination in sciarids.

PMID- 11223882
TI  - Ectopeptidases in pathophysiology.
AB  - Ectopeptidases are transmembrane proteins present in a wide variety of tissues
      and cell types. Dysregulated expression of certain ectopeptidases in human
      malignancies suggests their value as clinical markers. Ectopeptidase interaction
      with agonistic antibodies or their inhibitors has revealed that these ectoenzymes
      are able to modulate bioactive peptide responses and to influence growth,
      apoptosis and differentiation, as well as adhesion and motility, all functions
      involved in normal and tumoral processes. There is evidence that ectopeptidase
      mediated signal transduction frequently involves tyrosine phosphorylation.
      Combined analyses of gene organization and regulation of ectopeptidases by
      various physiological factors have provided insights into their structure
      function relationships. Understanding the roles of ectopeptidases in
      pathophysiology may have implications in considering them as therapeutic targets.

PMID- 11223883
TI  - The neprilysin (NEP) family of zinc metalloendopeptidases: genomics and function.
AB  - Neprilysin (NEP), a thermolysin-like zinc metalloendopeptidase, plays an
      important role in turning off peptide signalling events at the cell surface. It
      is involved in the metabolism of a number of regulatory peptides of the mammalian
      nervous, cardiovascular, inflammatory and immune systems. Examples include
      enkephalins, tachykinins, natriuretic and chemotactic peptides. NEP is an
      integral plasma membrane ectopeptidase of the M13 family of zinc peptidases.
      Other related mammalian NEP-like enzymes include the endothelin-converting
      enzymes (ECE-1 and ECE-2), KELL and PEX. A number of novel mammalian homologues
      of NEP have also recently been described. NEP family members are potential
      therapeutic targets, for example in cardiovascular and inflammatory disorders,
      and potent and selective inhibitors such as phosphoramidon have contributed to
      understanding enzyme function. Inhibitor design should be facilitated by the
      recent three-dimensional structural solution of the NEP-phosphoramidon complex.
      For several of the family members, however, a well-defined physiological function
      or substrate is lacking. Knowledge of the complete genomes of Caenorhabditis
      elegans and Drosophila melanogaster allows the full complement of NEP-like
      activities to be analysed in a single organism. These model organisms also
      provide convenient systems for examining cell-specific expression, developmental
      and functional roles of this peptidase family, and reveal the power of functional
      genomics.

PMID- 11223884
TI  - Recent progress in the biology, chemistry and structural biology of DNA
      glycosylases.
AB  - Since the discovery in 1974 of uracil DNA glycosylase (UDG), the first member of
      the family of enzymes involved in base excision repair (BER), considerable
      progress has been made in the understanding of DNA glycosylases, the polypeptides
      that remove damaged or mispaired DNA bases from DNA. We also know the enzymes
      that act downstream of the glycosylases, in the processing of abasic sites, in
      gap filling and in DNA ligation. This article covers the most recent developments
      in our understanding of BER, with particular emphasis on the mechanistic aspects
      of this process, which have been made possible by the elucidation of the crystal
      structures of several glycosylases in complex with their respective substrates,
      substrate analogues and products. The biological importance of individual BER
      pathways is also being appreciated through the inactivation of key BER genes in
      knockout mouse models.

PMID- 11223885
TI  - Evolution of the human menopause.
AB  - Menopause is an evolutionary puzzle since an early end to reproduction seems
      contrary to maximising Darwinian fitness. Several theories have been proposed to
      explain why menopause might have evolved, all based on unusual aspects of the
      human life history. One theory is that menopause follows from the extreme
      altriciality of human babies, coupled with the difficulty in giving birth due to
      the large neonatal brain size and the growing risk of child-bearing at older
      ages. There may be little advantage for an older mother in running the increased
      risk of a further pregnancy when existing offspring depend critically on her
      survival. An alternative theory is that within kin groups menopause enhances
      fitness by producing post-reproductive grandmothers who can assist their adult
      daughters. Such theories need careful quantitative assessment to see whether the
      fitness benefits are sufficient to outweigh the costs, particularly in
      circumstances of relatively high background mortality typical of ancestral
      environments. We show that individual theories fail this test, but that a
      combined model incorporating both hypotheses can explain why menopause may have
      evolved.

PMID- 11223887
TI  - Causes and consequences of hypoxia and acidity in tumour microenvironments.

PMID- 11223886
TI  - Anterior pituitary hormones, stress, and immune system homeostasis.
AB  - An extensive, and controversial, literature concluding that prolactin (PRL),
      growth hormone (GH), insulin-like growth factor-I (IGF-I), and thyroid hormones
      are critical immunoregulatory factors has accumulated. However, recent studies of
      mice deficient in the production of these hormones or expression of their
      receptors indicate that there are only a few instances in which these hormones
      are required for lymphocyte development or antigen responsiveness. Instead, a
      case is made that their primary role is to counteract the effects of negative
      immunoregulatory factors, such as glucocorticoids, which are produced when the
      organism is subjected to major stressors. The immunoprotective actions of PRL,
      GH, IGF-I, and/or thyroid hormones in these instances may ensure immune system
      homeostasis and reduce the susceptibility to stress-induced disease. These immuno
      enhancing effects could be exploited clinically in instances where the immune
      system is depressed due to illness or various treatment regimens.

PMID- 11223888
TI  - A biologist looks at the study of consciousness.

PMID- 11223889
TI  - Rat ventral prostate xanthine oxidase bioactivation of ethanol to acetaldehyde
      and 1-hydroxyethyl free radicals: analysis of its potential role in heavy alcohol
      drinking tumor-promoting effects.
AB  - The ability of the ventral prostate cytosolic fractions to biotransform ethanol
      to acetaldehyde and 1-hydroxyethyl (1HEt) radicals was tested. Acetaldehyde
      formation was determined by GC-FID analysis in the head space of incubation
      mixtures. 1HEt was determined by spin trapping with PBN followed by extraction,
      silylation of the adduct and GC-MS of the product. Prostate cytosol was able to
      biotransform ethanol to acetaldehyde in the presence of NADH, hypoxanthine,
      xanthine, caffeine, theobromine, theophylline, and 1,7-dimethylxanthine but not
      in the presence of N-methylnicotinamide. All these biotransformations were
      inhibited by allopurinol and were sensitive to heating for 5 min at 100 degrees
      C. The biotransformation of ethanol to acetaldehyde in the presence of purines as
      cosubstrates was accompanied by the formation of hydroxyl and 1HEt radicals as
      detected by GC-MS, and the process was inhibited by allopurinol. Results suggest
      that prostate cytosolic xanthine oxidase is able to bioactivate ethanol to
      acetaldehyde and free radicals. The potential of these processes to be involved
      in tumor-promoting effects of heavy alcohol drinking in conjunction with high
      meat and/or purines consumption is analyzed. Multifactorial epidemiological
      studies considering that possibility might be convenient. Teratogenesis Carcinog.
      Mutagen. 21:109-119, 2001.

PMID- 11223890
TI  - Action of valproic acid on Xenopus laevis development: teratogenic effects on
      eyes.
AB  - Valproic acid (VPA) is an anticonvulsive drug used in the treatment of epilepsy.
      Teratogenic effects of VPA have been described in different animal species. In
      this study, we investigate the effects of VPA on the development of Xenopus
      laevis embryos, by short pulse treatments (4 h) with relation to the dose and the
      stage of exposure to the drug. We exposed Xenopus embryos from blastula to stage
      32 to three different doses of VPA (0.25, 5, and 10 mM) and we allowed these to
      develop until the controls reached stage 47. The embryos became more sensitive
      during the stages of neurulation, as observed in mouse and differently from
      Amblystoma, in which the more severe effects were produced by treatments at
      blastula stage. The malformations observed were similar to those described in
      mammals and other amphibians and consisted in developmental delay, perturbation
      of neural crest migration, and somite segmentation. We also observed abnormal
      development of the retina, which had never been described for VPA treatments.
      Therefore we analyzed the relation between VPA-induced eye malformations and the
      expression of Pax-6. We examined VPA-treated Xenopus embryos by whole mount in
      situ hybridization for mis-expression of Pax-6 in correlation with eye anomalies.
      Our results are consistent with the hypothesis that different members of Pax gene
      family are candidate target of VPA teratogenic action and in particular the
      decreased level of Pax-6 expression, shown by Northern blot analysis, is
      responsible for the retinal malformations we observed in VPA-treated Xenopus
      embryos. Teratogenesis Carcinog. Mutagen. 21:121-133, 2001.

PMID- 11223891
TI  - I. The modulatory effect in genotoxic responses due to age and duration of PHT
      therapy in epileptic patients.
AB  - Sister chromatid exchange (SCE) frequency has been studied from the peripheral
      blood lymphocyte cultures of 42 epileptic patients on the anticonvulsant drug
      phenytoin (PHT) for 3 months and their follow-up (6 and 9 months), of 33
      epileptics who had not started therapy (PHT-untreated), and of 40 normal healthy
      controls, all in the same age group, i.e., 10-30 years. PHT-treated epileptic
      patients at all three durations of therapy (3, 6, and 9 months) showed higher SCE
      frequency (P < 0.001) than healthy controls and PHT-untreated patients. There was
      no significant difference in SCE frequency between control and PHT-untreated
      patients, suggesting that disease is not associated with an increased frequency
      of SCEs. The frequency of SCEs seems to be influenced by an age factor, when
      older treated patients (21-30 years) showed higher SCE frequencies at 3 and 6
      months (P < 0.001) and 9 months (P < 0.05) than the younger age group (10-20
      years). SCE frequency increased linearly with the duration of therapy, i.e., from
      3 months to 9 months. No correlation was found between SCE frequency and sex with
      respect to controls, PHT-untreated, and PHT-treated subjects. In conclusion, the
      modulating effect on SCE frequencies elicited by age and duration of therapy has
      been clearly demonstrated by SCE mean analysis. Teratogenesis Carcinog. Mutagen.
      21:135-149, 2001.

PMID- 11223892
TI  - II. An altered proliferation response due to the anticonvulsant phenytoin (PHT)
      in epileptic patients.
AB  - Lymphocyte proliferation kinetics (LPK) is an end point used in genetic
      toxicology that was proposed as an alternative for the screening of
      anticonvulsant drugs. The effect of phenytoin (PHT) was investigated on the
      mitotic and proliferation indices in cultured blood lymphocytes of 33
      sporadically collected untreated and 42 PHT-treated epileptics, where the
      duration of treatment was 3, 6, and 9 months, and 40 control subjects (age range
      10-30 years). PHT induced mitotic delays and decreased the mitotic index. A
      significant heterogeneity of the first, second and the third metaphases between
      treated and untreated groups was revealed. A reduction of the proliferation index
      (P < 0.001) and proliferation delay per cycle (P < 0.001) was also observed.
      There was little variation between the controls and untreated patients (P >
      0.05). The results have confirmed that PHT can affect responses leading to
      genotoxicity. Teratogenesis Carcinog. Mutagen. 21:151-164, 2001.

PMID- 11223893
TI  - Effect of antioxidant flavonoids and a food mutagen on lymphocytes of a
      thalassemia patient without chelation therapy in the Comet assay.
AB  - Thalassemia remains a significant health problem in Europe, the Middle East, and
      Asia. In such patients, generally high iron levels make free oxygen radicals
      accessible, for example, through Fenton-type chemistry, and generate superoxide
      and hydroxyl radicals. Increased oxygen radical capacity is known to be
      associated with cancer and ageing. It was shown in previous studies that
      peripheral blood lymphocytes from a sickle/beta thal double heterozygote-sickle
      phenotype, thalassemia patient, not yet on chelation therapy, were more sensitive
      to the effects of oxygen radicals and iron salts than lymphocytes from normal
      controls. Iron overload in thalassemia patients can result from dietary
      absorption. It was considered that with other dietary agents, such as food
      mutagens and flavonoids, the thalassemia patient might also show increased
      sensitivity to the effects of these agents. The present study, therefore,
      compared the effects of the food mutagen/carcinogen, 3-amino-1-methyl-5H
      pyrido(4,3-b)indole (Trp-P-2), in fresh or frozen normal human peripheral
      lymphocytes with frozen lymphocytes from the same thalassemia patient. The
      lymphocytes from the thalassemia patient showed an approximately two-fold
      increase in sensitivity. When a combination of Tryp-P-2, with either quercitin or
      kaempferol, was compared in frozen lymphocytes and lymphocytes from the
      thalassemia patient, a two-fold increase in sensitivity was also maintained.
      Responses to Trp-P-2 were reduced to untreated control levels at the highest
      doses of quercitin and kaempferol, and were highly significantly different by
      comparison with Trp-P-2 alone (P<0.001). The flavonoids acted in an
      antigenotoxic/antioxidant manner. Sensitivity was slightly increased with
      kaempferol by comparison with quercitin. At low concentrations of the flavonoids
      there was some evidence of an exacerbation of response, perhaps due to a switch
      to pro-oxidant status. This exacerbation of response at low doses of flavonoids
      has been seen in earlier studies with normal lymphocytes. Teratogenesis Carcinog.
      Mutagen. 21:165-174, 2001.

PMID- 11223894
TI  - Protective effect of thiourea, a hydroxyl-radical scavenger, on curcumin-induced
      chromosomal aberrations in an in vitro mammalian cell system.
AB  - Natural dietary antioxidants are extensively studied for their ability to protect
      cells from damage to DNA, protein, and lipids induced by antitumor agents or
      radiation that leads to the generation of free radical in normal cells in vivo
      and in vitro. Curcumin is a natural antioxidant known to possess therapeutic
      properties and has been reported to scavenge free radicals and to inhibit
      clastogenesis in mammalian cells. However, curcumin has been reported to induce a
      significant increase in the frequency of chromosomal aberrations in Chinese
      hamster ovary (CHO) cells. To investigate whether the clastogenic activity of
      curcumin in CHO cells in culture can be ascribed to a pro-oxidant behavior,
      mediated by free radical generation, experiments were carried out with the
      combination of curcumin (15 microg/ml) and thiourea (10, 20, or 40 microg/ml), a
      potent hydroxyl radical scavenger. The results showed that the clastogenic action
      of curcumin was statistically decreased in a dose-dependent manner in the
      presence of thiourea. These data have shown that curcumin-induced chromosomal
      damage in CHO cells can be mediated by hydroxyl radical generation in the present
      experimental conditions. Teratogenesis Carcinog. Mutagen. 21:175-180, 2001.

PMID- 11223895
TI  - Chemoprevention of benzene-induced bone marrow and pulmonary genotoxicity.
AB  - Our earlier studies documented the ability of 7,8-diacetoxy-4-methylcoumarin
      (DAMC) to cause irreversible inhibition of cytochrome P-450 linked mixed function
      oxidases (MFO) mediated by membrane bound DAMC: protein transacetylase. Since P
      450 catalyzed oxidation of benzene is crucial to its toxic effects, the action of
      DAMC and related analogues were considered promising in preventing the
      genotoxicity due to benzene. For this purpose rats were pretreated with various
      acetoxy-4-methylcoumarins (test compounds), which was followed by the
      administration of benzene either intratracheally (IT) or intraperitoneally (IP),
      and sacrificed 26 h after the injection of benzene. The incidence of micronuclei
      (MN) in bone marrow (BM) and lung (LG) were assessed by light and fluorescent
      microscopy, respectively. A dose-dependent induction of MN in BM and LG cells was
      observed in rats administered with benzene. A significant reduction in benzene
      induced MN in BM and LG was observed as a result of DAMC administration to rats;
      a higher dose of DAMC resulted in greater inhibition of clastogenic action of
      benzene as revealed by MN incidence. 7,8-dihydroxy-4-methylcoumarin (DHMC), the
      deacetylated product of DAMC, demonstrated relatively lesser potency to inhibit
      the clastogenic action of benzene. This observation is consistent with the
      ability of DAMC to inhibit the formation of benzene oxide as well as to scavenge
      the oxygen radicals formed during the course of benzene metabolism. The fact that
      DHMC can only scavenge the oxygen radicals and is ineffective in inhibiting
      benzene oxidation in vivo explains the reduced capability of dihydroxy coumarin
      to prevent MN due to benzene. 7-Acetoxy-4-methylcoumarin (MAC) inhibits the MN
      due to benzene being roughly 50% of that produced by DAMC. DAMC is also effective
      in normalizing the cell cycle alterations produced by benzene in BM and LG. These
      observations further substantiate our hypothesis that the biological effects of
      acetoxy coumarins are mediated by the action of membrane bound transacetylase
      that catalyzes the acetylation of concerned proteins. Teratogenesis Carcinog.
      Mutagen. 21:181-187, 2001.

PMID- 11223896
TI  - Type I error in sample size re-estimations based on observed treatment
      difference.
AB  - Sample size re-estimation based on an observed difference can ensure an adequate
      power and potentially save a large amount of time and resources in clinical
      trials. One of the concerns for such an approach is that it may inflate the type
      I error. However, such a possible inflation has not been mathematically
      quantified. In this paper the mathematical mechanism of this inflation is
      explored for two-sample normal tests. A (conditional) type I error function based
      on normal data is derived. This function not only provides the quantification but
      also gives mathematical mechanisms of possible inflation in the type I error due
      to the sample size re-estimation. Theoretically, based on their decision rules
      (certain upper and lower bounds), people can calculate this function and exactly
      visualize the changes in type I error. Computer simulations are performed to
      ensure the results. If there are no bounds for the adjustment, the inflation is
      evident. If proper adjusting rules are used, the inflation can be well
      controlled. In some cases the type I error can even be reduced. The trade-off is
      to give up some 'unrealistic power'. We investigated several scenarios in which
      the mechanisms to change the type I error are different. Our simulations show
      that similar results may apply to other distributions.

PMID- 11223897
TI  - Sample size re-estimation - journey for a decade.

PMID- 11223899
TI  - Sure outcomes of random events: a model for clinical trials.
AB  - We consider the outcomes of a clinical trial as determined by one, or several,
      possibly hidden causes. This paper proposes a statistical model that allows such
      a distinction of causes not only for the main, or therapeutic, effects but also
      for the side, or toxic, effects. More specifically, we focus on trials where the
      effects are naturally dichotomized, that is, where the health of a patient has
      improved or not, and where a specific adverse effect has occurred or not. A case
      study provides an example of the way this model can help to solve some problems
      of suspected drug toxicity. Finally, the model is shown to be a part of a
      hierarchy of models and the way to select a best model is investigated.

PMID- 11223900
TI  - A sensitivity analysis for subverting randomization in controlled trials.
AB  - In some randomized controlled trials, subjects with a better prognosis may be
      diverted into the treatment group. This subverting of randomization results in an
      unobserved non-compliance with the originally intended treatment assignment.
      Consequently, the estimate of treatment effect from these trials may be biased.
      This paper clarifies the determinants of the magnitude of the bias and gives a
      sensitivity analysis that associates the amount that randomization is subverted
      and the resulting bias in treatment effect estimation. The methods are
      illustrated with a randomized controlled trial that evaluates the efficacy of a
      culturally sensitive AIDS education video.

PMID- 11223901
TI  - Sample size calculations for the two-sample problem using the multiplicative
      intensity model.
AB  - In this paper we propose formulae for calculating the expected number of events
      or, alternatively, the required trial duration, for clinical trials involving two
      treatment groups in which patients may potentially experience multiple events and
      the data will be analysed using a multiplicative intensity (MI) model. We use a
      partial likelihood-based approach and examine in detail two MI models: one that
      includes a binary treatment variable as the only covariate and a three-state
      Markov process model in which a binary time-varying covariate is added to the
      previous model. For the simpler model, our formula coincides with those derived
      by Cook using full likelihood methods. We present applications of the derived
      formulae to chronic granulomatous disease and breast cancer data sets.

PMID- 11223903
TI  - A mixed effects model for the analysis of ordinal longitudinal pain data subject
      to informative drop-out.
AB  - We extend the model of Pulkstenis et al. that models binary longitudinal data,
      subject to informative drop-out through remedication, to the ordinal response
      case. We present a selection model shared-parameter approach that specifies mixed
      models for both ordinal response and discrete survival time to remedication. In
      this fashion, the random parameter present in both models completely
      characterizes the relationship between response and time to remedication inducing
      their conditional independence. With a log-log link function for both response
      and study 'survival', as well as specification of a log-gamma distribution for
      the random effect, we obtain a closed-form expression for the marginal log
      likelihood of response and time to remedication that does not require
      approximation or numerical integration techniques. A data analysis is performed
      and simulation results presented which support the consistency of parameter and
      standard error estimates.

PMID- 11223902
TI  - Quantifying and documenting prior beliefs in clinical trials.
AB  - Collecting and documenting subjective prior beliefs from knowledgeable clinicians
      about the potential results of a clinical trial has many advantages. Two large
      trials of prophylactic treatments in an HIV-positive population are used as
      examples. The trials recruited patients of primary care physicians and compared
      treatments which were in use in clinical practice. Opinions about these trials
      were elicited from 58 practising HIV clinicians. It is shown how the documented
      opinions can be used to augment the monitoring process; the prior opinions are
      updated with interim data using approximate Bayesian methods to give posterior
      opinions incorporating interim results. These posterior opinions can be used by
      the monitoring board to anticipate the clinicians' reaction to the results.
      Eliciting prior beliefs is also ethically important for documenting the nature of
      the uncertainty or equipoise. Important information is provided for the informed
      consent process and Institutional Review Board (IRB).

PMID- 11223904
TI  - Latent class marginal regression models for modelling youthful drug involvement
      and its suspected influences.
AB  - In longitudinal behavioural studies, it is common to have multiple categorical
      indicators for measuring a theoretical construct of interest. A latent class
      model is presented that accounts for the structure in a set of correlated,
      categorical variables measured at discrete time periods, drawing information from
      these variables to form a smaller number of latent classes. The dependence of the
      resulting latent class model parameters on suspected factors over time is
      simultaneously modelled using a baseline-category logistic regression model.
      Estimation of the model parameters is achieved using an estimating equations
      procedure. A motivating example is provided from a longitudinal study of
      suspected linkages between monitoring or supervision by parents and the
      occurrence of drug use behaviours in an epidemiologic sample of school-attending
      youths.

PMID- 11223905
TI  - A comparison of methods to detect publication bias in meta-analysis.
AB  - Meta-analyses are subject to bias for many of reasons, including publication
      bias. Asymmetry in a funnel plot of study size against treatment effect is often
      used to identify such bias. We compare the performance of three simple methods of
      testing for bias: the rank correlation method; a simple linear regression of the
      standardized estimate of treatment effect on the precision of the estimate; and a
      regression of the treatment effect on sample size. The tests are applied to
      simulated meta-analyses in the presence and absence of publication bias. Both one
      sided and two-sided censoring of studies based on statistical significance was
      used. The results indicate that none of the tests performs consistently well.
      Test performance varied with the magnitude of the true treatment effect,
      distribution of study size and whether a one- or two-tailed significance test was
      employed. Overall, the power of the tests was low when the number of studies per
      meta-analysis was close to that often observed in practice. Tests that showed the
      highest power also had type I error rates higher than the nominal level. Based on
      the empirical type I error rates, a regression of treatment effect on sample
      size, weighted by the inverse of the variance of the logit of the pooled
      proportion (using the marginal total) is the preferred method.

PMID- 11223907
TI  - Using a combination of reference tests to assess the accuracy of a diagnostic
      test by A. Alonzo and M. Pepe, Statistics in Medicine 1999; 18: 2987-3003.

PMID- 11223909
TI  - Perspectives for mass spectrometry and functional proteomics.

PMID- 11223910
TI  - Selected reviews on mass spectrometric topics.

PMID- 11223911
TI  - Quantitative imaging of tyrosine hydroxylase and calmodulin in the human brain.
AB  - The distributions of tyrosine hydroxylase and calmodulin in adult normal
      postmortem human brain were analyzed quantitatively. Consecutive coronal sections
      were obtained from the anterior area of the right hemisphere and were stained
      immunohistochemically for tyrosine hydroxylase and calmodulin. Stained sections
      were divided into approximately 3 million microareas at 50 microm intervals, and
      the immunohistochemical fluorescence intensity in each area was measured by a
      human brain mapping analyzer, which is a microphotometry system for analysis of
      the distribution of neurochemicals in a large tissue slice. Immunoreactive
      staining of tyrosine hydroxylase and calmodulin was observed in almost all brain
      regions, but its intensity varied. Relatively high levels of calmodulin were
      observed in brain regions with high levels of tyrosine hydroxylase, though high
      levels of tyrosine hydroxylase were not always observed in brain regions where
      high levels of calmodulin were distributed. In particular, high levels of both of
      tyrosine hydroxylase and calmodulin were distributed in the caudate nucleus and
      putamen. Previously it was shown that tyrosine hydroxylase was activated and
      dopamine synthesis was enhanced in the neostriatum region in mice and rats by the
      intracerebroventricular administration of calcium through a calmodulin-dependent
      system. The present results combined with these previous findings suggest that
      the activity of tyrosine hydroxylase in the caudate nucleus and putamen of humans
      may also be regulated by a calcium/calmodulin-dependent system.

PMID- 11223912
TI  - N-methyl-D-aspartate receptor-mediated mitochondrial Ca(2+) overload in acute
      excitotoxic motor neuron death: a mechanism distinct from chronic neurotoxicity
      after Ca(2+) influx.
AB  - Mitochondrial uptake of Ca(2+) has recently been found to play an important role
      in glutamate-induced neurotoxicity (GNT) as well as in the activation of Ca(2+)
      dependent molecules, such as calmodulin and neuronal nitric oxide synthase
      (nNOS), in the cytoplasm. Prolonged exposure to glutamate injures motor neurons
      predominantly through the activation of Ca(2+)/calmodulin-nNOS, as previously
      reported, and is, in part, associated with the pathogenesis of amyotrophic
      lateral sclerosis (ALS). In the present study, we investigated how mitochondrial
      uptake of Ca(2+) is involved in GNT in spinal motor neurons. Acute excitotoxicity
      induced by exposure to 0.5 mM glutamate for 5 min was found in both motor and
      nonmotor neurons in cultured spinal cords from rat embryos and was dependent on
      extracellular Ca(2+) and on N-methyl-D-aspartate (NMDA) receptor activation.
      Mitochondrial uncouplers markedly blocked acute excitotoxicity, and membrane
      permeable superoxide dismutase mimics attenuated acute excitotoxicity induced by
      glutamate and NMDA but not by alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionate (AMPA) or kainate. Fluorimetric analysis showed that mitochondrial
      Ca(2+) was elevated promptly with subsequent accumulation of reactive oxygen
      species (ROS) in the mitochondria. An NMDA receptor antagonist and a
      mitochondrial uncoupler eliminated the increase in fluorescence of mitochondrial
      Ca(2+) and ROS indicators. These data indicate that acute excitotoxicity in
      spinal neurons is mediated by mitochondrial Ca(2+) overload and ROS generation
      through the activation of NMDA receptors. This mechanism is different from that
      of chronic GNT.

PMID- 11223913
TI  - Tissue plasminogen activator protects hippocampal neurons from oxygen-glucose
      deprivation injury.
AB  - We have previously shown that tissue plasminogen activator (tPA) participates in
      the neurotoxicity of microglial conditioned medium (MgCM). Killing of hippocampal
      neurons by MgCM was prevented by both plasminogen activator inhibitor-1 (PAI-1)
      and anti-tPA antibody. An N-methyl-D-aspartate (NMDA) receptor blocker protected
      neurons from MgCM, suggesting that this subtype of glutamate receptor is
      involved. Whereas glutamate receptor-mediated events are important in cerebral
      ischemia and tPA has previously been shown to enhance excitotoxicity in
      hippocampus, we hypothesized that tPA would exaggerate oxygen glucose deprivation
      (OGD) injury in cultures of hippocampal neurons. Dissociated rat hippocampal
      cells were grown under conditions designed to optimize neuronal growth while
      minimizing glial replication. At 7--10 days, cultures were subjected to OGD for
      2.5 hr. Recombinant human tPA (1,000 IU) was added immediately after OGD.
      Viability was assessed 24 hr later. Viable, apoptotic, and necrotic cells were
      classified and quantified based on staining patterns of acridine orange and
      ethidium bromide under fluorescence microscopy. tPA alone did not alter neuronal
      integrity. OGD produced significant neuronal death (viability reduced by 45%, P <
      0.001). tPA completely protected OGD-exposed cultures. Potential mechanisms of
      tPA protection were explored. Whereas tPA antibody abolished the protective
      effect of tPA, its proteolytic inhibitor PAI-1 did not alter the effect. The
      effect of tPA was tested in separate free radical and excitatory amino acid
      insults. It did not protect neurons from hydrogen peroxide (1 microM), S-nitro
      acetylpenicillamine (10 microM), glutamate (50 microM), or NMDA (10 microM)
      damage but significantly attenuated injury caused by 250 microM kainate. We
      conclude that tPA is capable of protecting hippocampal neurons from OGD by a
      nonproteolytic action. The mechanism of protection was not defined, although
      attenuation of AMPA/kainate glutamate receptors may play a role.

PMID- 11223914
TI  - Role of spermine in amyloid beta-peptide-associated free radical-induced
      neurotoxicity.
AB  - The polyamines, relatively low-molecular-weight aliphatic compounds, are the main
      inducers of eukaryotic cell growth and proliferation. Although polyamine
      requirements for cell growth are well defined, their role is still enigmatic. We
      have previously reported that amyloid beta-peptide (A beta), the main constituent
      of senile plaques in Alzheimer's disease (AD) brain, is toxic to neurons through
      a free radical-dependent oxidative stress mechanism and that A beta(1--42), the
      principal form of A beta in AD brain, causes an increase in polyamine metabolism
      manifested by up-regulated polyamine uptake and increased ornithine decarboxylase
      (ODC) activity. Both effects were prevented by the free radical scavenger vitamin
      E. Spermine has been reported to function directly as a free radical scavenger.
      In the current study, we aimed to address whether up-regulation of polyamine
      metabolism is a defense against, or a result of, A beta-induced oxidative stress
      by investigating the capability of spermine to quench A beta-associated free
      radicals in solution and to assert a protective function of spermine in neuronal
      culture against A beta. Pretreatment of cultured neurons with spermine prior to A
      beta exposure failed to prevent A beta-induced cell death. Indeed, A beta plus
      spermine added to cultured neurons was even more neurotoxic than either agent
      alone. Additionally, inhibition of the polyamine synthesis by
      difluoromethylornithine (DFMO) did not protect cells from A beta-induced free
      radical toxicity, and stimulation of the synthesis of putrescine and spermine by
      the aminopropyltransferase inhibitor S-adenosyl-1,8-diamino-thiooctane (AdoDATO),
      rather, further enhanced A beta-induced toxicity. Although spermine is capable of
      scavenging free radicals generated by A beta in solution as measured by electron
      paramagnetic resonance (EPR) spectroscopy, the up-regulated transport of
      exogenously added spermine together with A beta may lead to overaccumulation of a
      cellular spermine pool, with resulting enhanced neurotoxicity.

PMID- 11223915
TI  - Nerve growth factor prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced
      cell death via the Akt pathway by suppressing caspase-3-like activity using PC12
      cells: relevance to therapeutical application for Parkinson's disease.
AB  - Nerve growth factor (NGF) mediates a variety of nerve cell actions through
      receptor tyrosine kinase TrkA. It has been revealed that the Akt pathway
      contributes to the prevention of apoptosis. It is thought that Parkinson's
      disease involves apoptosis, and NGF prevents apoptosis in an in vivo model
      system. However, there is no evidence that the Akt pathway helps to prevent
      parkinsonism. Here, we report that NGF prevents apoptosis induced by 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP) in PC12 cells as an in vitro model
      system of parkinsonism and that this survival effect diminishes on addition of
      LY294002, a specific inhibitor of phosphatidylinositol 3-kinase.
      Immunocytochemical analysis revealed that 1 mM MPTP-treated cells or dominant
      negative Akt-expressing cells, to which were added NGF and MPTP, undergo
      apoptosis. Moreover, the caspase-3-like activity is increased by addition of MPTP
      or MPTP with NGF and LY294002. The importance of another signal pathway is shown
      by PD98059, a specific inhibitor of MAP kinase (MAPK) kinase, but PD98059 does
      not alter the survival effect in this model system. These results indicate that
      the Akt pathway helps to prevent parkinsonism by suppressing caspase-3-like
      activity, but the MAPK pathway is not involved in the NGF-dependent survival
      enhancing effect in this model system.

PMID- 11223916
TI  - Characterization of the neurotrophic interaction between nerve growth factor and
      secreted alpha-amyloid precursor protein.
AB  - The expression and secretion of amyloid precursor protein (beta APP) is increased
      in rat cerebral cortices that have been denervated by subcortical lesions of the
      nucleus basalis of Meynert. The physiological role of the secreted beta APP in
      response to this injury has not been established. We have previously shown that
      secreted beta APP produced by alpha-secretase activity (sAPP(alpha)) potentiates
      the neuritogenic activity of nerve growth factor (NGF) in vitro on naive PC12
      cells. In this investigation, we have further characterized the neurotrophic
      interaction of NGF and sAPP(alpha) using differentiated PC12 cells and rat
      primary cortical neurons. NGF required the expression of beta APP to maintain a
      neuronal phenotype. Reduction of endogenous beta APP expression by introduction
      of antisense oligonucleotides in the presence of NGF resulted in loss of neurites
      from differentiated PC12 cells but no apparent cell death. Addition of exogenous
      sAPP(alpha) (60--200 pM) potentiated the protective activity of NGF in serum
      deprived differentiated PC12 cells as determined by retention of neurites and
      cell viability. In addition, exogenous sAPP(alpha) increased neuron viability in
      both short-term (3 days) cortical neuron cultures grown in the absence of serum
      and in long-term (9 days) cultures grown with serum. Disruption of the insulin
      signaling pathway by reduction of IRS-1 expression inhibited the ability of
      sAPP(alpha) to potentiate neurotrophic activity. These observations suggest that
      sAPP(alpha) acts as an injury-induced neurotrophic factor that interacts with NGF
      to enhance neuronal viability using the insulin signaling pathway.

PMID- 11223917
TI  - Low concentrations of 1-methyl-4-phenylpyridinium ion induce caspase-mediated
      apoptosis in human SH-SY5Y neuroblastoma cells.
AB  - There is growing evidence that apoptotic mechanisms underlie the
      neurodegeneration leading to Parkinson's disease. 1-Methyl-4-phenylpyridinium ion
      (MPP(+)), the active metabolite of the parkinsonism-inducing drug MPTP, induced
      apoptosis in cultures of human SH-SY5Y neuroblastoma cells. Nuclear
      fragmentation, DNA laddering, and a 20% decrease in viability were seen after a 4
      day incubation with 5 microM MPP(+). Cell viability decreased by 40% at 100
      microM MPP(+), but the degree of apoptosis was not correlatively increased. The
      MPP(+)-induced apoptosis was completely prevented by the broad caspase inhibitor
      zVAD.fmk but not by the caspase-8 inhibitor IETD.fmk. Furthermore, MPP(+) had no
      effect on the levels of Fas or Fas-L, suggesting lack of activation of the Fas
      L/Fas/caspase-8 pathway of apoptosis. There was no evidence of mitochondrial
      dysfunction at 5 microM MPP(+): No differences were seen in transmembrane
      potential or in cytochrome c release from controls. At 100 microM MPP(+), the
      mitochondrial potential decreased, and cytoplasmic cytochrome c and caspase-9
      activation increased slightly. At both low and high concentrations of MPP(+),
      VDVADase and DEVDase activities increased. We conclude that MPP(+) can induce
      caspase-mediated apoptosis, which is prevented by caspase inhibition, at
      concentrations lower than those needed to trigger mitochondrial dysfunction and
      closer to those found in the brains of MPTP-treated animals.

PMID- 11223918
TI  - Calcium ionophore A23187 specifically decreases the secretion of beta-secretase
      cleaved amyloid precursor protein during apoptosis in primary rat cortical
      cultures.
AB  - Alzheimer's disease (AD) is characterized by the degeneration and loss of
      neurons, intracellular neurofibrillary tangles and the accumulation of
      extracellular senile plaques consisting mainly of beta-amyloid (A beta). A beta
      is generated from the amyloid precursor protein (APP) by sequential beta- and
      gamma-secretase cleavage. Alternatively, APP may be cleaved within the A beta
      region by alpha-secretase, preventing A beta formation. Here we investigated APP
      processing and secretion in primary neurons, using either colchicine or the
      calcium ionophore A23187 to induce apoptosis. Cell viability was determined by
      MTT measurements and apoptosis was further confirmed by annexin V and propidium
      iodide staining. We found that exposure to A23187 significantly decreased the
      secretion of soluble beta-secretase cleaved APP (beta-sAPP) in a caspase
      dependent manner, although the secretion of total soluble APP beta sAPP) did not
      change. In addition, caspase inhibition restored cell viability to control
      levels. Exposure to colchicine did not change the amount of either secreted beta
      sAPP or total sAPP and caspase inhibition was only partially able to restore cell
      viability. We conclude that calcium homeostasis is an important apoptotic
      effector specifically affecting the beta-secretase cleavage of APP.

PMID- 11223919
TI  - Upregulation of ICAM-1 and MCP-1 but not of MIP-2 and sensorimotor deficit in
      response to traumatic axonal injury in rats.
AB  - The pathophysiology of traumatic axonal injury (TAI) is only partially
      understood. In this study, we investigated the inflammatory response as well as
      the extent of neurological deficit in a rat model of traumatic brain injury
      (TBI). Forty-two adult rats were subjected to moderate impact-acceleration brain
      injury and their brains were analyzed immunohistochemically for ICAM-1 expression
      and neutrophil infiltration from 1 hr up to 14 days after trauma. In addition,
      the chemotactic factors MIP-2 and MCP-1 were measured in brain homogenates by
      ELISA. For evaluating the neurological deficit, three sensorimotor tests were
      applied for the first time in this model. In the first 24 hr after trauma, the
      number of ICAM-1 positive vessels increased up to 4-fold in cortical and
      subcortical regions compared with sham operated controls (P < 0.05). Maximal ICAM
      1 expression (up to 8-fold increase) was detected after 4 days (P < 0.001 vs. 24
      hr), returning to control levels in all brain regions by 7 days after trauma. MCP
      1 was elevated between 4 hr and 16 hr post-injury as compared with controls. In
      contrast, neither neutrophil infiltration nor elevation of MIP-2, both events
      relevant in focal brain injury, could be detected. In all neurological tests, a
      significant deficit was observed in traumatized rats as compared with sham
      operated animals from Day 1 post-injury (grasping reflex of the hindpaws: P <
      0.001, vibrissae-evoked forelimb placing: P = 0.002, lateral stepping: P =
      0.037). In conclusion, after moderate impact acceleration brain injury ICAM-1
      upregulation has been demonstrated in the absence of neutrophil infiltration and
      is paralleled by a selective induction of chemokines, pointing out that
      individual and distinct inflammatory events occur after diffuse vs. focal TBI.

PMID- 11223920
TI  - Zinc homeostasis in the brain of adult rats fed zinc-deficient diet.
AB  - Zinc concentration and (65)Zn uptake in the brain of rats fed zinc-deficient diet
      for 12 weeks were examined, based on a previous finding of the impairment of
      learning behavior by the zinc deprivation. Zinc concentrations in the brain,
      except for the hippocampal formation, did not decrease significantly in zinc
      deficient rats, whereas zinc concentration in the liver of the zinc-deficient
      rats was approximately half that of control rats. When zinc-deficient rats were
      subjected to brain autoradiography with (65)Zn, (65)Zn concentration in any brain
      region of zinc-deficient rats was significantly higher than in control rats 6
      days after injection of (65)ZnCl(2). The increase rate of (65)Zn concentration in
      the brain by the zinc deprivation was approximately 150%, and was similar to
      those in the liver and serum, suggesting that dietary zinc deprivation may cause
      a scarcity of zinc in the brain, in addition to the peripheral tissues such as
      the liver. These results indicate that the adult brain is responsive to dietary
      zinc deprivation. In the brain of zinc-deficient rats, the increase rate of
      (65)Zn concentration in the hippocampal formation seemed to be low compared to
      those in other brain regions. The hippocampal formation may be the most
      responsive to dietary zinc deprivation in the adult brain. The present finding
      demonstrates that zinc homeostasis in the brain is altered by chronically dietary
      zinc deprivation.

PMID- 11223921
TI  - Symmetry of priapulids (Priapulida). 1. Symmetry of adults.
AB  - Priapulids possess a radial symmetry that is remarkably reflected in both
      external morphology and internal anatomy. It results in the appearance of 25
      radial (a number divisible by five) symmetry summarized as a combination of
      nonaradial, octaradial, and octaradial (9+8+8) symmetries of scalids. The radial
      symmetry is a secondary appearance considered as an evolutionary adaptation to a
      lifestyle within the three-dimensional environment of bottom sediment. The eight
      anteriormost, or primary, scalids retain their particular position because of
      their innervation directly from the circumpharyngeal brain. As a result of a
      combination of the octaradial symmetry of primary scalids, pentaradial symmetry
      of teeth, and the 25-radial symmetry of scalids, the initial bilateral symmetry
      remains characterized by the single sagittal plane.

PMID- 11223922
TI  - Symmetry of priapulids (Priapulida). 2. Symmetry of larvae.
AB  - Larvae of priapulids are characterized by radial symmetry evident from both
      external and internal characters of the introvert and lorica. The bilaterality
      appears as a result of a combination of several radial symmetries: pentaradial
      symmetry of the teeth, octaradial symmetry of the primary scalids, 25-radial
      symmetry of scalids, biradial symmetry of the neck, and biradial and decaradial
      symmetry of the trunk. Internal radiality is exhibited by musculature and the
      circumpharyngeal nerve ring. Internal bilaterality is evident from the position
      of the ventral nerve cord and excretory elements. Externally, the bilaterality is
      determined by the position of the anal tubulus and two shortened midventral rows
      of scalids bordering the ventral nerve cord. The lorical elements define the
      biradial symmetry that is missing in adult priapulids. The radial symmetry of
      larvae is a secondary appearance considered an evolutionary adaptation to a
      lifestyle within the three-dimensional environment of the benthic sediment.

PMID- 11223923
TI  - Surface ultrastructure of the gills of the mullets Mugil curema, M. liza and M.
      platanus (Mugilidae, Pisces).
AB  - Mugil curema, M. liza, and M. platanus were collected from the southeastern and
      southern coast of Brazil. The second gill arches were analyzed by scanning
      electron microscopy and histology. The highest density of chloride and mucus
      secreting cells was observed in the gill filaments of M. liza and M. platanus.
      Spines are scarce and were found only in the pharyngeal region of M. curema. The
      dorsal angle of curvature of the simple projections is most reduced in the rakers
      of M. liza and M. platanus. The raker borderline on the internal side of the
      arches of M. curema has grooves that do not occur in the other two species. On
      the external side of the branchial arches, the borders of the rakers of M. liza
      and M. platanus are smooth. The shape of the rakers is characteristic for each
      species: in M. curema, it resembles the letter "D"; in M. liza, it is
      trapezoidal, and in M. platanus, it is triangular. Thus there is a morphologic
      similarity between M. liza and M. platanus, and both differ from M. curema. All
      three species show elongated and extremely elaborated rakers that are placed next
      to each other and turned toward the opercular cavity. There are few taste buds
      and only several mucus-secreting cells along the whole pharyngeal region. These
      characteristics suggest that these species do not select food chemically but
      obtain it mechanically with the rakers and aggregate it with mucus.

PMID- 11223924
TI  - Neuroglandular synapses in the pharynx of the sea anemone Aiptasia pallida
      (Cnidaria, Anthozoa).
AB  - Scanning and transmission electron microscopy of the pharynx of the sea anemone
      Aiptasia pallida revealed a heavily ciliated epidermis and two types of gland
      cells not known previously to be innervated. By tracing serial cross sections of
      the pharynx, we located and characterized two types of neuroglandular synapses
      (i.e., those having clear vesicles and those with dense-cored vesicles). The
      diameters of the vesicles at each synapse were averaged; clear vesicles ranged
      from 70 to 103 nm in diameter and were observed at synapses to both mucous and
      zymogenic gland cells. Dense-cored vesicles ranged from 53 to 85 nm in diameter
      and were observed at synapses to two mucous gland cells. One mucous gland cell
      had three neuroglandular synapses, one with clear vesicles and two with dense
      cored vesicles. The occurrence of either clear or dense-cored vesicles at
      neuroglandular synapses suggests that at least two types of neurotransmitter
      substances control the secretion of mucus in the sea anemone pharynx. To date,
      only clear vesicles have been observed at a neurozymogenic gland cell synapse in
      the pharynx. No evidence of immunoreactivity to phenylethanolamine-N-methyl
      transferase was observed at neuroglandular synapses, suggesting that adrenaline
      is not a transmitter in the pharynx of A. pallida.

PMID- 11223925
TI  - Caudal vertebral development and morphology in three salamanders with complex
      life cycles (Ambystoma jeffersonianum, Hemidactylium scutatum, and Desmognathus
      ocoee).
AB  - We describe caudosacral and caudal vertebral morphology across life history
      stages in three caudate amphibians: Ambystoma jeffersonianum (Ambystomatidae),
      Desmognathus ocoee (Plethodontidae: Desmognathinae), and Hemidactylium scutatum
      (Plethodontidae: Plethodontinae). All three species have aquatic larvae, but
      adults differ in habitat and predator defense strategy. Predator defense includes
      tail autotomy in D. ocoee and H. scutatum but not A. jeffersonianum. Of the
      species that autotomize, H. scutatum has a specialized constriction site at the
      tail base. We investigated whether aquatic larvae exhibit vertebral features
      similar to those previously described for aquatic adults and examined the effect
      of metamorphosis, if any, on vertebral morphology and the ontogeny of specialized
      vertebral features associated with tail autotomy. Interspecific comparisons of
      cleared-and-stained specimens indicate that vertebral morphology differs
      dramatically at hatching and that caudosacral and caudal vertebrae undergo
      continuous ontogenetic change throughout larval, metamorphic, and juvenile
      periods. Larvae and juveniles of H. scutatum do not exhibit adult vertebral
      features associated with constricted-base tail autotomy. The pond-type larvae of
      A. jeffersonianum and H. scutatum have tapering centrum lengths posterior to the
      sacrum. This pattern is functionally associated with aquatic locomotion. The
      stream-type larvae of D. ocoee undergo enhanced regional growth in the anterior
      tail such that the anterior caudal centra become longer than the preceding
      caudosacral centra. With the exception of the first two caudal vertebrae, a
      similar growth pattern occurs in H. scutatum adults. We hypothesize that enhanced
      growth of the anterior caudal segments is associated with tail elongation and
      autotomy.

PMID- 11223926
TI  - Descriptions of the mature spermatozoa of the lizards Crotaphytus bicinctores,
      Gambelia wislizenii (Crotaphytidae), and Anolis carolinensis (Polychrotidae)
      (Reptilia, Squamata, Iguania).
AB  - The spermatozoa of Crotaphytus bicinctores and Gambelia wislizenii
      (Crotaphytidae), and Anolis carolinensis (Polychrotidae) exhibit the squamate
      autapomorphies of a single perforatorium extending anteriorly from the apical tip
      of the paracrystalline subacrosomal cone, the presence of an epinuclear electron
      lucent region, and extension of the fibrous sheath into the midpiece. Crotaphytid
      sperm differ from those of polychrotids in several respects, including: the
      structure of the perforatorium, the size of the epinuclear electron-lucent
      region, aspects of the acrosome complex, the arrangement and structure of
      intermitochondrial dense bodies, and in the distance the fibrous sheath extends
      into the midpiece. The sperm of C. bicinctores, G. wislizenii, and A.
      carolinensis are most similar to those of the agamids and phrynosomatids examined
      to date. No spermatozoal autapomorphies for Crotaphytidae or Polychrotidae were
      found. The condition of having the intermitochondrial dense bodies arranged in
      regular incomplete rings is tentatively defined as a synapomorphy of Iguania
      (although modified in Chamaeleonidae). Spermatozoal ultrastructure offers no
      characters that justify the separation of Iguanidae (sensu lato) into several
      separate families.

PMID- 11223927
TI  - Histological study of the development of the embryo and early larva of
      Oreochromis niloticus (Pisces: Cichlidae).
AB  - The developmental stages of Oreochromis niloticus are similar to those described
      in other mouth-breeding tilapias except that, as in zebrafish, no cavity was
      found in the blastula. Variation in the rate of development of the embryo and
      larva of O. niloticus was found within a clutch of eggs as well as between
      clutches. Hatching glands are described for the first time in tilapias. They are
      widely distributed within the ectoderm covering the head, body, tail, and surface
      of the yolk sac near its attachment to the embryo. Timing of larval development
      is similar to that in other mouthbrooding tilapias, but is slower than that found
      in substrate-spawning tilapias. A pneumatic duct connects the swimbladder to the
      digestive tract and swimbladder inflation and initiation of feeding occurs at
      about the same time. The digestive tract of the larva 8 and 9 days after
      fertilization is similar to that found in the adult, except that there are no
      digestive glands. An endocrine pancreatic islet was first seen 76 h after
      fertilization. A prominent thymus gland is present at 100 h. Hematopoietic tissue
      develops in the vicinity of the pronephros during early larval development. A
      spleen develops later, 7 days after fertilization.

PMID- 11223928
TI  - Ontogenetic shift in mouth opening mechanisms in a catfish (Clariidae,
      Siluriformes): a response to increasing functional demands.
AB  - During ontogeny, larval fish have to deal with increasing nutritional and
      respiratory demands as they grow. As early ontogeny is characterized by an
      increasing complexity of moving structural elements composing a fish skull, some
      constraints will have to be met when developing mechanisms, which enable feeding
      and respiration, arise at a certain developmental stage. This article focuses on
      the presence/absence of a possible functional response in mouth opening during
      ontogeny in Clarias gariepinus. Some reflections are given, based on
      morphological data, as well as related function-analysis data from the
      literature. Starting shortly after hatching, a total of up to five different
      mouth opening mechanisms may become functional. Of these, three may remain
      functional in the adult. As could be expected, the apparatuses that enable these
      mechanisms show an increase in complexity, as well as a putative improvement in
      mouth opening capacity. Initially, two consecutive mechanisms may allow a
      restricted depression of the lower jaw (both passively and actively).
      Synchronously, two more mechanisms may arise, which involve the coupling of the
      hyoid depression to the mouth opening. At about 11 mm SL a fifth mechanism
      becomes established, better known as the opercular mouth opening mechanism. An
      overlapping chronology of functionality of the different mechanisms, as well as
      differences in efficiencies, could be an indication of the absence of a true
      critical period in C. gariepinus (at least in relation to mouth opening), as well
      as the possible presence of a shift in feeding type. Finally, the coupling of the
      chronology of the shift in mouth opening mechanisms and several morphological,
      behavioral, and physiological changes during ontogeny, related to feeding and
      respiration, make it possible to distinguish five important phases in the early
      life history of C. gariepinus.

PMID- 11223929
TI  - Cytoarchitectonic study of the brain of a perciform species, the sea bass
      (Dicentrarchus labrax). I. The telencephalon.
AB  - A cytoarchitectonic analysis of the telencephalon of the sea bass Dicentrarchus
      labrax, based on cresyl violet-stained serial transverse sections, is presented.
      Rostrally, the brain of the sea bass is occupied by sessile olfactory bulbs
      coupled to telencephalic hemispheres. The olfactory bulbs comprise an olfactory
      nerve fiber layer, a glomerular layer, an external cellular layer, a secondary
      olfactory fiber layer, and an internal cellular layer. Large terminal nerve
      ganglion cells are evident in the caudomedial olfactory bulbs. We recognized 22
      distinct telencephalic nuclei which were classified in two main areas, the
      ventral telencephalon and the dorsal telencephalon. The ventral telencephalon
      displays four periventricular cell masses: the dorsal, ventral, supracommissural,
      and postcommissural nuclei; and four migrated populations: the lateral, central,
      intermediate, and entopeduncular nuclei. In addition, a periventricular cell
      population resembling the lateral septal organ reported in birds is observed in
      the ventral telencephalon of the sea bass. The dorsal telencephalon contains 13
      nuclei, which can be organized into five major zones: the medial part, dorsal
      part, lateral part and its ventral, dorsal, and posterior divisions, the central
      part, and posterior part. Based on histological criteria, two cell masses are
      recognized in the ventral division of the lateral part of the dorsal
      telencephalon. The nucleus taenia is found in the caudal area of the dorsal
      telencephalon, close to the ventral area. This study represents a useful tool for
      the precise localization of the neuroendocrine territories and for the tracing of
      the neuronal systems participating in the regulation of reproduction and
      metabolism in this species.

PMID- 11223930
TI  - Cytoarchitectonic study of the brain of a perciform species, the sea bass
      (Dicentrarchus labrax). II. The diencephalon.
AB  - The cytoarchitecture of nuclei in the preoptic area, ventral thalamus, dorsal
      thalamus, epithalamus, hypothalamus, posterior tuberculum, synencephalon, and
      pretectum and the accessory optic nuclei was analyzed in a perciform teleost, the
      sea bass Dicentrarchus labrax, by using serial sections stained with cresyl
      violet. In general, the cytoarchitecture of the preoptic area, ventral and dorsal
      thalamus, epithalamus, and synencephalon resembles the histological pattern of
      other teleosts. However, the parvocellular preoptic nucleus of sea bass has been
      subdivided into parvocellular and anteroventral parts for morphological and
      functional reasons. The hypothalamus of the sea bass seems to differ slightly
      from that of other teleosts. An elaborated lateral tuberal nucleus, with five
      subdivisions, and three different nuclei around the lateral recesses were
      recognized. A medial nucleus of the inferior lobe, which has been reported
      previously in the perciform Sparus aurata, is also present in the hypothalamus of
      sea bass but has not been described before in another advanced teleost. The
      organization of the pretectum and the accessory optic system is essentially
      similar in sea bass to that described in other perciforms with highly developed
      vision. The migrated portion of the posterior tuberculum of sea bass appears to
      differ from this region of the diencephalon in other teleosts. In sea bass, three
      cell masses that have been described previously only in the perciform Sparus
      aurata have been assigned to the migrated area of the posterior tuberculum. This
      study will provide the neuroanatomical basis for future morpho-functional studies
      to be done in the sea bass brain.

PMID- 11223931
TI  - Structural characteristics of the patagium of Ptychozoon kuhli (Reptilia:
      Gekkonidae) in relation to parachuting locomotion.
AB  - Ptychozoon kuhli is known for its parachuting/gliding capabilities. In this
      contribution, we document the allometric scaling properties of its patagium,
      accessory flaps and folds, and its total body surface area and compare them to
      similar attributes of the agamine lizard Draco volans. Ptychozoon kuhli has
      passive patagia that lack skeletal support and muscular control. Patagial area in
      P. kuhli is smaller than that in D. volans for individuals of identical snout
      vent length, but the accessory folds and flaps compensate for this shortfall and
      overall P. kuhli has equivalent total body surface area to D. volans for equally
      sized individuals. The structure of the patagium of Ptychozoon kuhli was
      investigated in terms of its scalation patterns and structural integrity, its
      relationship to the body wall and its mechanism of erection, and the distribution
      of mechanoreceptive sensilla across its surface. Scalation patterns and the
      internal architecture of the patagium indicate how its shape and form are
      maintained as it erects and becomes exposed to air flow. Its cross-sectional
      shape, together with that of the entire body indicates how it is able to behave
      as an airfoil. The distribution of sensilla across the patagial surface reflect
      positioning indicative of the monitoring of scale-to-scale contact on the dorsal
      surface, and possibly air pressure and flow on the ventral surface.

PMID- 11223932
TI  - Extraordinary case of matrotrophy in the African skink Eumecia anchietae.
AB  - The viviparous African skink, Eumecia anchietae, exhibits a matrotrophic fetal
      nutritional pattern. Until well after the limb bud stage, extravitelline
      nutritional provision is in the form of holocrine secretion originating from the
      stratified uterine epithelium of the uterine incubation chambers. Uterine
      secretions are absorbed by a specialized yolk sac ectoderm and chorioallantois
      through histotrophy. The yolk sac is not in close contact with the uterine lining
      from the limb bud stage onwards. The yolk sac ectoderm forms invaginations filled
      with uterine secretion and consists of a single layer of vacuolated hypertrophied
      cells bearing microvilli. The chorioallantois at the limb bud stage is extensive,
      well-vascularized, and not intimately associated with the uterine epithelium.
      Where the uterus is folded, the chorioallantois may interdigitate loosely.
      Chorionic cells are low to high columnar, clearly vacuolated, and bear
      microvilli. The allantoic layer consists primarily of squamous cells exhibiting
      villous projections. By the time embryos have well-defined digits, the
      specialized yolk sac ectoderm has regressed and the yolk sac lumen has been
      invaded by vitelline cells. The chorioallantois is very extensive and in areas
      greatly folded. Where it contacts the uterine epithelium, a proper
      chorioallantoic placenta is formed. Cell layers of the chorioallantois and
      uterine epithelium are thin and cuboidal to squamous in appearance. The
      chorioallantoic placenta is simple in structure, occurs throughout the incubation
      chamber, and is epitheliochorial in arrangement. It is unknown whether the
      placentome observed in other highly matrotrophic scincids is formed in late stage
      embryos of this species.

PMID- 11223933
TI  - c-Fos-related antigens in the central nervous system of an insect, Acheta
      domesticus.
AB  - Fos-related antigens (Fra) were detected in the nuclei of neurones in young adult
      Acheta domesticus female crickets by immunohistochemical analysis, using an
      antibody that recognizes the amino-acid sequence 127-152 of c-Fos protein.
      Specificity of Fra immunoreactivity was confirmed by Western blot analysis of
      nuclear extracts from neural tissues. A major immunoreactive doublet with an
      apparent molecular mass of 52,000/54,000 Da was detected in nuclear extracts.
      Immunostaining of the 52,000/54,000 Da doublet showed variations in intensity
      during the first 5 days following the imaginal molt. Staining was more intense
      between day 2 and day 4 when ecdysteroid titers were high. Expression of Fra was
      low in allatectomized (i.e., deprived of juvenile hormone and ecdysteroids) and
      ovariectomized (i.e., deprived of ecdysteroids) females as compared to control
      females. These results show the involvement of hormone-regulated process in
      expression of Fra. The effect of nociceptive stimulation on Fra expression was
      tested. Twenty minutes after removal of the ovipositor, a supplementary band with
      an apparent molecular mass of 70,000 Da appeared in the nuclear extracts, then
      decreased and disappeared totally after 45 min. Several other Fos-related
      antigens with different temporal patterns of expression were also detected.

PMID- 11223934
TI  - cDNA cloning and antibacterial activities of cecropin D-like peptides from Agrius
      convolvuli.
AB  - We have characterized full-length cDNAs encoding two isoforms of agriusin,
      cecropin D-like antibacterial peptide, present in the hemolymph of the immunized
      Agrius convolvuli larvae. The cloned cDNAs of agriusins 1 and 2 contain 331 and
      329 bp, respectively. The nucleotide sequencing of cDNAs showed that they encode
      62 amino acids, whose mature portion was deduced to consist of 38 amino acid
      residues with over 94% sequence identity. In the sequence homology search, mature
      agriusin 1 showed over 86 and 71% amino acid sequence homology with bactericidin
      4 from Manduca sexta and cecropin D from Hyalophora cecropia, respectively. Since
      it was demonstrated from the deduced amino acid sequences that the C-terminal
      residues of agriusins are followed by a Gly residue, two types of synthetic
      agriusin 1 (syn-agriusin 1 amide and acid) were prepared to verify if natural
      agriusin 1 is C-terminally amidated. From acid-urea PAGE and reversed phase HPLC
      profiles to compare two synthetic peptides, we could confirm that the C-terminal
      amino acid residue of natural agriusin 1, like several cecropins so far
      identified, is amidated. Finally, our antibacterial assay performed with two syn
      agriusins 1 revealed that there is little difference between antibacterial
      activities of both peptides against Gram-positive and Gram-negative bacteria.

PMID- 11223935
TI  - Involvement of adipokinetic hormone in the homeostatic control of hemolymph
      trehalose concentration in the larvae of Bombyx mori.
AB  - Prior to wandering, 5th instar larvae of the silkworm, Bombyx mori, maintain
      constant hemolymph titers of trehalose. Head ligation of day 3, 5th instar larvae
      significantly decreased the hemolymph trehalose concentrations, but the
      concentrations did not decrease in starved larvae. After being diluted by
      replacement of larval hemolymph with insect Ringer's solution, the trehalose
      concentrations recovered the initial levels in 90 min in the non-ligated larvae,
      while they were not restored in 90 min in the neck-ligated larvae. These results
      suggest that a head factor(s) with hypertrehalosemic activity is involved in the
      homeostatic control of hemolymph trehalose concentration. When adipokinetic
      hormone (AKH) was injected into neck-ligated larvae, the trehalose concentrations
      increased in 2 h and decreased thereafter. Repeated injections of AKH every 4 h
      maintained the concentrations for 12 h. These findings suggest that AKH induces a
      hypertrehalosemic response and is involved in the homeostasis of hemolymph
      trehalose concentration in the larval feeding period.

PMID- 11223936
TI  - In vitro metabolism of aflatoxin B1 by larvae of navel orangeworm, Amyelois
      transitella (Walker) (Insecta, Lepidoptera, Pyralidae) and codling moth, Cydia
      pomonella (L.) (Insecta, Lepidoptera, Tortricidae).
AB  - Larvae of the navel orangeworm (NOW), Amyelois transitella (Walker), a major pest
      of almonds and pistachios, and the codling moth (CM), Cydia pomonella (L.), the
      principal pest of walnuts and pome fruits, are commonly found in tree nut kernels
      that can be contaminated with aflatoxin, a potent carcinogen. The ability of
      larvae of these insects to metabolize aflatoxin B1 (AFB1) was examined. A field
      strain of NOW produced three AFB1 biotransformation products, chiefly aflatoxicol
      (AFL), and minor amounts of aflatoxin B2a (AFB2a) and aflatoxin M1 (AFM1). With
      AFL as a substrate, NOW larvae produced AFB1 and aflatoxicol M1 (AFLM1). A lab
      strain of CM larvae produced no detectable levels of AFB1 biotransformation
      products in comparison to a field strain which produced trace amounts of only
      AFL. Neither NOW nor CM produced AFB1-8,9-epoxide (AFBO), the principal
      carcinogenic metabolite of AFB1. In comparison, metabolism of AFB1 by chicken
      liver yielded mainly AFL, whereas mouse liver produced mostly AFM1 at a rate
      eightfold greater than AFL. Mouse liver also produced AFBO. The relatively high
      production of AFL by NOW compared to CM may reflect an adaptation to detoxify
      AFB1. NOW larvae frequently inhabit environments highly contaminated with fungi
      and, hence, aflatoxin. Only low amounts, if any, of this mycotoxin occur in the
      chief CM hosts, walnuts, and pome fruits. Characterizations of enzymes and co
      factors involved in biotransformation of AFB1 are discussed.

PMID- 11223937
TI  - Modulation of a lectin insecticidal activity by carbohydrates.
AB  - Lectins from plants present an insecticidal activity most probably through their
      carbohydrate binding properties; as a consequence, their toxicity should vary
      with the presence of a competitive sugar in the ingested food. In order to test
      this hypothesis, we performed competition experiments between insecticidal
      activity and carbohydrate binding. For this purpose, we used a lectin from
      Lathyrus ochrus and the specific carbohydrate for this protein, glucose. In
      toxicological tests with Drosophila melanogaster, we observed a decrease of
      lectin toxicity when glucose was added to the larva-rearing medium. This result
      suggests that the toxicity of the lectin is correlated to its ability to bind
      sugar in the insect digestive tract and stresses the importance of sugar
      composition of the nutriment used for toxicological testing of lectins or in
      genetically modified plants.

PMID- 11223938
TI  - Replication of minichromosomes in Saccharomyces cerevisiae is sensitive to
      histone gene copy number and strain ploidy.
AB  - We have characterized a defect in the mitotic transmission of plasmid
      minichromosomes in yeast strains deleted for the more highly expressed pair of
      histone H3 and H4 genes. Several observations indicate that an impairment in DNA
      replication contributes to the decrease in minichromosome stability. First, the
      maintenance of ARS plasmids that lack centromeres was also defective. Second, the
      addition of multiple ARS elements suppressed the defect in plasmid maintenance.
      Third, a synergistic increase in plasmid loss rate was seen when a plasmid
      containing an inefficient mutated ARS was tested in a strain deleted for histone
      genes, implying an interaction between ARS activity and the histone gene
      deletion. These results support the existence of a histone-dependent step in the
      initiation of DNA replication. We find that the stability of native chromosomes
      is not affected in strains deleted for histone genes. We propose that reduced
      histone H3 and H4 protein decreases the efficiency of initiation at ARS elements
      on plasmids and chromosomes, but that the presence of multiple origins on
      chromosomes compensates for the reduced efficiency. We find that decreased
      minichromosome stability is suppressed by increases in strain ploidy. The greater
      stability due to ploidy increases is not due to a relative increase in the
      expression of histone genes. We discuss models for the effect of strain ploidy on
      minichromosome maintenance.

PMID- 11223939
TI  - Isolation of a Candida albicans gene, tightly linked to URA3, coding for a
      putative transcription factor that suppresses a Saccharomyces cerevisiae aft1
      mutation.
AB  - A pathogen such as C. albicans needs an efficient mechanism of iron uptake in an
      iron-restricted environment such as is the human body. A ferric-reductase
      activity regulated by iron and copper, and analogous to that in S. cerevisiae,
      has been described in C. albicans. We have developed an in-plate protocol for the
      isolation of clones that complement an aft1 mutation in S. cerevisiae that makes
      cells dependent on iron for growth. After transformation of S. cerevisiae aft1
      with a C. albicans library, we have selected clones that grow in conditions of
      iron deficiency and share an identical plasmid, pIRO1, with a 4500 bp insert
      containing the URA3 gene and an ORF (IRO1) responsible for the suppression of the
      iron dependency. IRO1 does not show homology with AFT1 or with other sequences in
      the databases. Northern analysis demonstrates constitutive expression of IRO1.
      CAI4, a C. albicans strain isolated as Deltaura3, also has a deletion of the 3'
      half of IRO1, and displays in YNB medium similar phenotypic characteristics to S.
      cerevisiae aft1 mutant strains. Therefore, we consider IRO1 as a gene of C.
      albicans involved in the utilization of iron. However, in extreme conditions of
      iron deprivation, CAI4 seems to activate alternative mechanisms of iron uptake
      that allow a better growth than the wild strain SC5314. Analysis of its predicted
      protein sequence is in agreement with a role of Iro1p as a transcription factor.

PMID- 11223940
TI  - Seryl-tRNA synthetase is not responsible for the evolution of CUG codon
      reassignment in Candida albicans.
AB  - A number of Candida species translate the standard leucine-CUG codon as serine
      using a novel ser-tRNA(CAG). This tRNA, which has an unusual anticodon stem-loop
      structure, has been implicated in the evolution of this codon reassignment.
      However, such a sense codon reassignment might also require a change in the
      specificity of the cognate aminoacyl tRNA-synthetase, in this case the ser-tRNA
      synthetase. Here we describe the cloning and sequence analysis of the C. albicans
      seryl aminoacyl-tRNA synthetase (CaSerRS) gene (CaSES1). The predicted CaSerRS
      sequence shows a significant level of amino acid identity to SerRs from other
      organisms and fully complements a S. cerevisiae SerRS null strain without any
      apparent defect in growth rate. This suggests that the SerRS recognizes and
      charges S. cerevisiae ser-tRNAs with similar efficiency to that of the S.
      cerevisiae SerRS. Using an antibody raised against CaSerRS, we also demonstrate
      the presence of SerRS in a range of Candida spp. showing CUG codon reassignment.
      We conclude that the key element in CUG reassigment in Candida spp. is the tRNA
      that decodes the CUG codon rather than a SerRS structural change. The nucleotide
      sequence of the CaSES1 gene has been deposited at GenBank under Accession No.
      AF290915.

PMID- 11223941
TI  - YJL159w does encode Pir2/Hsp150.
AB  - In this paper we compare the sequence of the gene HSP150/PIR2, independently
      determined by two different groups, with that present in the yeast database as
      YJL159w, determined within the Yeast Sequencing Project. Although YJL159w is
      believed to encode Hsp150/Pir2, there are important differences between the amino
      acid sequence coded by this ORF and that of HSP150/PIR2. To find out if this
      divergence is due to strain polymorphism or to a possible sequencing error, we
      have analysed the diverging zone of this ORF in three strains and have found it
      entirely consistent with the sequence reported as HSP150/PIR2, concluding that
      the divergence is probably due to a sequencing error in YJL159w.

PMID- 11223942
TI  - Functional Analysis of six novel ORFs on the left arm of Chromosome XII of
      Saccharomyces cerevisiae reveals three of them responding to S-starvation.
AB  - Six novel Open Reading Frames (ORFs) located on the left arm of the chromosome
      XII (YLL061w, YLL060c, YLL059c, YLL058w, YLL057c and YLL056c) have been analysed
      using either short-flanking homology (SFH) or long-flanking homology (LFH) gene
      replacement. Sporulation and tetrad analysis showed none of these ORFs to be
      essential for vegetative growth. The standard EUROFAN growth tests failed to
      reveal any obvious phenotypes resulting from deletion of each of the ORFs.
      Bioinformatic analysis revealed that YLL061w is probably an amino acid permease
      for S-methylmethionine and that YLL060c encodes a glutathione transferase which
      is involved in cellular detoxification, while YLL058w may play a role in sulphur
      containing amino-acid metabolism, YLL057c in sulphonate catabolism and YLL056c in
      stress response. The transcription of three ORFs (YLL061w, YLL057c and YLL056c)
      has been shown to increase more than 10-fold under sulphate starvation.
      Replacement cassettes, comprising the kanMX marker flanked by each ORF's promoter
      and terminator regions, were cloned into pUG7. All the cognate clones, were
      generated using direct PCR products amplified from genomic DNA or using gap
      repair. All clones and strains produced have been deposited in the EUROFAN
      genetic stock centre (EUROSCARF, Frankfurt).

PMID- 11223943
TI  - Role of adenosine kinase in Saccharomyces cerevisiae: identification of the ADO1
      gene and study of the mutant phenotypes.
AB  - Sequencing of the Saccharomyces cerevisiae genome revealed an open reading frame
      (YJR105w) encoding a putative protein highly similar to adenosine kinases from
      other species. Disruption of this gene (renamed ADO1) affected utilization of S
      adenosyl methionine (AdoMet) as a purine source and resulted in a severe
      reduction of adenosine kinase activity in crude extracts. Furthermore, knock-out
      of ADO1 led to adenosine excretion in the medium and resistance to the toxic
      adenosine analogue cordycepin. From these data we conclude that ADO1 encodes
      yeast adenosine kinase. We also show that ADO1 does not play a major role in
      adenine utilization in yeast and we propose that the physiological role of
      adenosine kinase in S. cerevisiae could primarily be to recycle adenosine
      produced by the methyl cycle.

PMID- 11223944
TI  - The deletion of CaVPS34 in the human pathogenic yeast Candida albicans causes
      defects in vesicle-mediated protein sorting and nuclear segregation.
AB  - A Candida albicans null mutant of the phosphatidylinositol (PI) 3-kinase gene
      (CaVPS34) involved in virulence was examined by different microscopical
      techniques. We observed that vacuoles of the Cavps34 null mutant were
      considerably enlarged and electron-transparent. An interesting result obtained by
      transmission electron microscopy analysis of Cavps34 mutant cells was the
      aberrant patch-like accumulation of vesicles, which were localized in the
      periplasm close to the plasma membrane. We assume that the vesicles result from
      missorted prevacuolar compartments. In contrast to the accumulations of the
      specific endocytic dye FM4-64 in the vacuole membrane in C. albicans wild-type
      strains (ring staining pattern), the Cavps34 mutant strain showed a staining of
      punctuate structures, possibly multivesicular bodies (MVB), that are scattered
      all over the cell. This defect indicates a late block in endocytic vesicle
      transport. Measurement of the total activity of carboxypeptidase Y revealed
      significantly lower activity in Cavps34 mutant cells. This may indicate that
      carboxypeptidase Y is not properly activated as a result of mislocalization due
      to the lack of Vps34p. The deletion of the CaVPS34 gene caused disturbance of
      normal nuclear migration, which suggests that in the Cavps34 mutant the cell-size
      mediated control process of cell division is affected.

PMID- 11223945
TI  - Subtelomeric sequence from the right arm of Schizosaccharomyces pombe chromosome
      I contains seven permease genes.
AB  - The sequence has been determined of 80 888 bp of contiguous subtelomeric DNA,
      including the isp5 gene, from the right arm of chromosome I of
      Schizosaccharomyces pombe; 27 open reading frames (ORFs) longer than 100 codons
      are present, giving a density of one gene per 3.0 kb. Seven of the predicted
      proteins are members of the major facilitator superfamily (MFS) of transport
      proteins, including four amino acid permease homologues, bringing this family of
      amino acid permease sequences to 17 in Sz. pombe, and a phylogenetic analysis is
      presented. Also encoded is an allantoate permease homologue, a sulphate permease
      homologue and a probable urea active transporter. Predicted non-membrane proteins
      include a 1-aminocyclopropane-1-carboxylate deaminase (ACC deaminase), a class
      III aminotransferase, serine acetyltransferase, protein-L-isoaspartate O
      methyltransferase, alpha-glucosidase, alpha-galactosidase, esterase/lipase,
      oxidoreductase of the short-chain dehydrogenase/reductase (SDR) family, aldehyde
      dehydrogenase, formamidase, amidase, flavohaemoprotein, a putative translation
      initiation inhibitor and a protein with similarity to a filamentous fungal
      conidiation-specific protein. The remaining six ORFs are likely to encode
      proteins, either because they have sequence similarity with hypothetical proteins
      or because they are known to be transcribed. Introns are scarce in the sequenced
      region: only three ORFs contain introns, with only one having multiple introns.
      The sequenced region also contains a single Tf1 transposon long terminal repeat
      (LTR). The sequence is derived from cosmid clones c869, c922 and c1039 and has
      been submitted to the EMBL database under entries SPAC869 (Accession No.
      AL132779), SPAC922 (AL133522) and SPAC1039 (AL133521).

PMID- 11223946
TI  - A history of research on yeasts 3: Emil Fischer, Eduard Buchner and their
      contemporaries, 1880-1900.
AB  - Through the discovery of Buchner, Biology was relieved of another fragment of
      mysticism. The splitting up of sugar into CO2 and alcohol is no more the effect
      of a "vital principle" than the splitting up of cane sugar by invertase. (Jacques
      Loeb 1906 [138] p.22.)

PMID- 11223948
TI  - Antisense targeting of c-fos transcripts inhibits serum- and TGF-beta 1
      stimulated PAI-1 gene expression and directed motility in renal epithelial cells.
AB  - Plasminogen activator inhibitor type-1 (PAI-1), the major regulator of
      pericellular plasmin generation, and the c-FOS transcription factor are expressed
      by migrating cells in response to monolayer wounding. Induced c-fos and PAI-1
      transcripts were evident within 30 min and 2 h, respectively, of scrape injury to
      confluent, growth-arrested, cultures of NRK epithelial cells. Since c-FOS/AP-1
      DNA-binding activity modulates both basal and inducible modes of PAI-1 gene
      control, and AP-1 motif binding factors were present in quiescent as well as
      stimulated NRK cells, a model of directionally regulated cell movement (migration
      into scrape-denuded "wounds") was used to assess the consequences of c-fos
      transcript targeting on PAI-1 expression and cell motility. This in vitro model
      of epithelial injury closely approximated in vivo wound repair with regard to the
      spatial and temporal emergence of cohorts of cells involved in migration,
      proliferation, and PAI-1 expression. Stable cell lines (NRKsof) were generated by
      transfection of parental NRK cells with a c-fos antisense expression vector.
      Serum-inducible c-fos transcripts and PAI-1 protein levels were significantly
      attenuated in NRKsof transfectants relative to parental controls or cells
      transfected with a neo(R) vector without the sof insert. NRKsof cells had a
      markedly impaired ability to repair scrape-generated monolayer wounds under
      basal, serum-stimulated, or TGF-beta 1-supplemented culture conditions. Since
      injury closure and PAI-1 induction were attenuated in c-fos antisense cells, it
      was important to clarify the role of specific AP-1 sites in serum-mediated PAI-1
      transcription. PAI-1 "promoter"-driven CAT reporter expression was assessed
      within the real time of serum-stimulated PAI-1 induction. A segment of the PAI-1
      promoter corresponding to nucleotides -533 to -764 upstream of the transcription
      start site functioned as a prominent serum-responsive region (SSR). The 9-fold
      increase in CAT mRNA levels attained with the -533 to -764 bp PAI-1 SRR ligated
      to a minimal PAI-1 promoter (i.e., 162 bp of 5' flanking sequence containing the
      basal transcription complex) closely approximated the serum-induced
      transcriptional activity of a fully responsive (1,230 bp) PAI-1 promoter
      construct as well as the endogenous PAI-1 gene. AP-1-like, CTF/NF-1-like, and AP
      2 sites were identified in the SRR. The SRR AP-1 motif was homologous to the
      sequence TGACACA that mapped between nucleotides -740 and -703 in the human PAI-1
      gene, a region essential for growth factor-inducible PAI-1 transcription. While
      the functionality of this AP-1 site in wound-regulated PAI-1 synthesis remains to
      be determined, antisense c-fos transcripts effectively attenuated PAI-1 induction
      and basal as well as growth factor-stimulated cell locomotion, indicating that
      expression of both the PAI-1 and c-fos genes is necessary for wound-initiated NRK
      cell migration.

PMID- 11223950
TI  - Dynamics of alpha-actinin in focal adhesions and stress fibers visualized with
      alpha-actinin-green fluorescent protein.
AB  - Motile cells undergo changes in cell adhesion, behavior, and shape that are
      mediated by small-scale cytoskeletal rearrangements. These rearrangements have
      proven difficult to follow quantitatively in living cells, without disrupting the
      very structures and delicate protein balances under study. We have expressed a
      prominent cytoskeletal protein, alpha-actinin, as a fusion with green fluorescent
      protein (alpha AGFP), and have followed this construct's movements within
      transfected mouse Swiss 3T3 and BALB/c fibroblasts. alpha AGFP was expressed at
      low levels to avoid overexpression artifacts. alpha AGFP localized to cellular
      structures, including stress fibers, focal adhesions, microspikes, and
      lamellipodia. High-resolution video-microscopy revealed that the alpha AGFP
      construct could be seen relocating to focal adhesions early in their formation
      and shortly thereafter to stress-fiber dense bodies. By Fluorescent Recovery
      After Photo-bleaching (FRAP) techniques, alpha AGFP was found to have similar
      exchange rates and protein stability in focal adhesions and stress fibers
      (despite the known differences in protein composition in these two structures).
      This raises the possibility that the two structures share common key regulatory
      factors and may not be as affected by protein-protein binding interactions as
      previously suggested. Additionally, the exchange rates revealed by video
      microscopy and FRAP analysis of alpha AGFP are more rapid than those reported
      previously, which were obtained using microinjection of large excesses of
      fluorescently-tagged protein.

PMID- 11223949
TI  - The role of actin filaments and microtubules in hepatocyte spheroid self
      assembly.
AB  - Cultured rat hepatocytes self-assemble into three-dimensional structures or
      spheroids that exhibit ultrastructural characteristics of native hepatic tissue
      and enhanced liver-specific functions. The spheroid formation process involves
      cell translocation and changes in cell shape, indicative of the reorganization of
      the cytoskeletal elements. To elucidate the function of the cytoskeleton,
      hepatocytes undergoing spheroid formation were treated with drugs that disrupt
      the different cytoskeletal components. Cytochalasin D, which targets the actin
      filaments, caused inhibition of spheroid formation. The role of microtubules in
      this process was assessed by incubating the cells with taxol or nocodazole.
      Perturbation of microtubules had minimal effects on spheroid assembly. Scanning
      electron micrographs showed no morphological differences between spheroids formed
      in control cultures and those formed in the presence of taxol or nocodazole. In
      addition, the effects of those agents on hepatocyte functions were investigated.
      Albumin secretion and cytochrome P450 2B1/2 activities of hepatocytes were
      comparable in spheroids formed in the presence of taxol or nocodazole to those
      formed in control cultures. The levels of these liver-specific activities were
      lower in cytochalasin D--treated cultures where only dispersed cells or cell
      clumps were found but spheroids had not found. Thus, hepatocytes require an
      intact actin network to self-assemble efficiently into functional tissue-like
      structures. Perturbation of the microtubule lattice does not impair the formation
      process. Events that transpire during hepatocyte spheroid self-assembly exhibit
      striking similarities to processes commonly observed in tissue morphogenesis. The
      results provide insight into the mechanisms that cells employ to organize into
      tissues and can contribute to our understanding of how to control the cellular
      assembly in tissue engineering and clinical applications.

PMID- 11223951
TI  - Microtubule integrity is essential for apical polarization and epithelial
      morphogenesis in the thyroid.
AB  - In this study, we examined the contribution of microtubules to epithelial
      morphogenesis in primary thyroid cell cultures. Thyroid follicles consist of a
      single layer of polarized epithelial cells surrounding a closed compartment, the
      follicular lumen. Freshly isolated porcine thyroid cells aggregate and reorganize
      to form follicles when grown in primary cultures. Follicular reorganization is
      principally a morphogenetic process that entails the assembly of biochemically
      distinct apical and basolateral membrane domains, delimited by tight junctions.
      The establishment of cell surface polarity during folliculogenesis coincided with
      the polarized redistribution of microtubules, predominantly in the developing
      apical poles of cells. Disruption of microtubule integrity using either
      colchicine or nocodazole caused loss of defined apical membrane domains, tight
      junctions and follicular lumina. Apical membrane and tight junction markers
      became randomly distributed at the outer surfaces of aggregates. In contrast, the
      basolateral surface markers, E-cadherin and Na(+),K(+)-ATPase, remained correctly
      localized at sites of cell-cell contact and at the free surfaces of cell
      aggregates. These findings demonstrate that microtubules play a necessary role in
      thyroid epithelial morphogenesis. Specifically, microtubules are essential to
      preserve the correct localization of apical membrane components within enclosed
      cellular aggregates, a situation that is also likely to pertain where lumina must
      be formed from solid aggregates of epithelial precursors.

PMID- 11223952
TI  - Cytokinesis failure in clathrin-minus cells is caused by cleavage furrow
      instability.
AB  - The role of membrane traffic during cell division has only recently begun to be
      investigated. A growing number of trafficking proteins seem to be involved in the
      successful completion of cytokinesis. Clathrin was the first trafficking protein
      to be shown to be essential for cytokinesis in Dictyostelium. Here we investigate
      the nature of the cytokinesis defect of Dictyostelium clathrin null cells. We
      found that adherent clathrin null cells do form cleavage furrows but cannot
      maintain a consistent rate of furrow ingression. Clathrin null cells are
      completely defective in cytokinesis when placed in suspension. In these
      conditions, the cells develop an abnormal division morphology that consists of
      two lateral "furrows" on either side of a bulging equatorial region. Cells
      expressing GFP-myosin II were examined at various stages of cytokinesis. Clathrin
      null cells show multiple defects in myosin organization and localization that
      parallel the striking failure in furrow morphology. We postulate that this
      morphology is the result of contraction at the rear of the presumptive daughter
      cells in concert with incomplete furrow ingression.

PMID- 11223954
TI  - Optimisation of the quantitative determination of chlormequat by matrix-assisted
      laser desorption/ionisation mass spectrometry.
AB  - The plant growth regulator chlormequat, an involatile quaternary ammonium salt,
      has been quantified by matrix-assisted laser desorption/ionisation time-of-flight
      mass spectrometry (MALDI-TOFMS). Restrictions for quantitative MALDI-TOFMS
      analysis, such as irreproducible crystallisation and unsatisfactory laser
      stability, have been overcome by the application of two synthesised isotopically
      labelled standards and the optimisation of the measurement protocol. Data
      acquisition at constant laser power was compared to data acquisition at
      approximately constant ion abundance of the relevant ions (analyte and internal
      standards). Data acquisition at constant ion abundance performed better and
      enabled a high number of consecutive firings to the same sample deposition area.
      Furthermore an increased sample-to-sample repeatability and a high
      reproducibility over several weeks without re-calibration have been attained by
      this method. Linearity over three orders of magnitude (0.05 to 30 ng/microL
      chlormequat), with a correlation coefficient of 0.9997, was achieved using [13C3]
      chlormequat as internal standard. Limit of detection and limit of determination
      were determined to be in the low pg/microL range for pure standard solutions.
      Thin-layer chromatography was applied for the removal of high amounts of choline,
      which is often present in plant tissue extracts and can adversely affect the
      ionisation and detection of chlormequat by MALDI-TOFMS. The use of two internal
      standards ([13C3]- and [2H9]-chlormequat) enabled direct quantification and
      simultaneous control of the recovery.

PMID- 11223953
TI  - Actin cytoskeleton reorganization of the apoptotic nurse cells during the late
      developmental stages of oogenesis in Dacus oleae.
AB  - In the present study, we demonstrate the actin cytoskeleton reorganization during
      nurse cells apoptosis of the olive fruit fly Dacus oleae. At the developmental
      stage 9A of oogenesis, the actin microfilaments are assembled in numerous ring
      canals and subcortically support all the nurse cells, as is shown by phalloidin
      FITC staining. During the following stages, 9B and 10A, this structural pattern
      remains the same. The developmental stage 10B is characterized by actin
      microfilament rearrangement and formation of actin cables that are symmetrically
      organized around the nurse cell nuclei. At stage 11, when the dumping process
      begins, these actin cables seem to retain each nurse cell nucleus in the cell
      center, away from blocking the ring canals. The early stage 12 is characterized
      by an asynchronous nurse cell nuclear chromatin condensation, while at late stage
      12 the actin cables become very thick, as adjacent ones overlap one another and
      traverse the disorganized apoptotic nurse cell nuclei that already have
      fragmented DNA, as is demonstrated by acridine orange staining and TUNEL assay.
      Finally, during stage 13, the apoptotic nuclear remnants are phagocytosed by the
      neighboring follicle cells. The data presented herein compared to previous
      reported results in Drosophila [Nezis et al., 2000: Eur J Cell Biol 79:610-620],
      demonstrate that actin cytoskeleton reorganization during nurse cell apoptosis is
      a developmentally regulated physiological mechanism, phylogenetically conserved
      in higher Dipteran.

PMID- 11223955
TI  - Ion fragmentation in an electrospray ionization mass spectrometer interface with
      different gases.
AB  - Nitrogen, argon, and krypton are used as curtain gases in an electrospray
      ionization mass spectrometer in an attempt to study the effect of these gases on
      the extent of ion fragmentation between the orifice and the skimmer of the
      interface region. A previously published collision model predicts that the degree
      of ion fragmentation increases with increasing mass of the curtain gas. However,
      the fragmentation yields are found to be the opposite to that expected. It is
      believed that the reversed trend with argon and krypton is caused by condensation
      of the gases within the free jet expansion between the orifice and the skimmer. A
      condensation parameter can be used to predict the degree of clustering of gases
      within a free jet expansion. When the condensation parameter is minimized, the
      predicted trend of fragmentation with mass is observed.

PMID- 11223956
TI  - Two-dimensional gel electrophoresis/matrix-assisted laser desorption/ionisation
      mass spectrometry of commercial bovine milk.
AB  - Proteins in commercial bovine milk have been separated by two-dimensional gel
      electrophoresis and examined by matrix-assisted laser desorption/ionisation mass
      spectrometry. Gel separation was conducted in two different pH gradients, 3-10
      and 6-11; the latter range resulted in a higher spot resolution and favoured the
      basic proteins. We have limited the time-of-flight mass spectrometry analysis to
      the linear mode to examine the capability of reliable relative molecular masses
      of the intact proteins in their characterisation. The present study draws
      attention to the difficulty of identifying basic proteins with low molecular
      masses (below 12000 Da) that are commonly encountered in milk samples.

PMID- 11223957
TI  - The use of particle beam mass spectrometry for the measurement of impurities in a
      nabumetone drug substance, not easily amenable to atmospheric pressure ionisation
      techniques.
AB  - Liquid chromatography/particle beam mass spectrometry (LC/PB-MS) was used for the
      structural elucidation of some impurities in nabumetone as this compound poorly
      ionises by atmospheric pressure ionisation (API) techniques. PB-MS was optimised
      for nabumetone and a sensitivity study was carried out. To obtain full scan
      electron ionisation spectra a minimum of 100 ng of compound on column was needed.
      By using 20 mg/mL solutions of nabumetone, impurities at levels of about 250 ppm
      mass fraction relative to nabumetone could be detected. Results were compared
      with LC/API-MS and previous GC/MS.

PMID- 11223958
TI  - Attachment of alkali cations on beta-D-glucopyranose: matrix-assisted laser
      desorption/ionization time-of-flight studies and ab initio calculations.
AB  - In matrix-assisted laser desorption/ionization mass spectrometry, carbohydrates
      ionize by attachment of an alkali cation, and the ion yield varies with the
      nature of the cation. In an attempt to contribute to the understanding of the
      mechanisms involved, we have conducted matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) experiments on the simple
      glucose molecule with the alkali cations Li+, Na+ and K+, and have also performed
      ab initio calculations. The calculations show that, for the most stable
      carbohydrate-cation geometry, the carbohydrate ring is twisted and the cation is
      coordinated to four oxygen atoms. Calculations also show that in these complexes
      the positions of the three cations are very similar, and the smaller the cation,
      the closer it is to the oxygen atoms. Finally, the calculated formation
      enthalpies of the different complexes agree with the experimental results
      obtained for the order of stability of these complexes.

PMID- 11223960
TI  - Study of the electrospray ionization mass spectrometry of the proton pump
      inhibiting drug Omeprazole.
AB  - A detailed analysis of the product ion spectrum generated from the protonated
      molecule under ESI-MS/MS conditions using a triple quadrupole mass spectrometer
      is reported for the gastrointestinal proton pump inhibitor Omeprazole.
      Unambiguous molecular composition data of the fragment ions were obtained with
      the aid of regioselectively 14C-, 34S- and 18O-labeled analogs. Attempts have
      been made to provide rational pathways for the formation of the fragment ions
      from four protonated omeprazole species. These results will facilitate the
      characterization of the complex metabolic fate of Omeprazole in humans, which
      involves the excretion of at least 50 metabolites.

PMID- 11223962
TI  - Determination of 4-hydroxytamoxifen in mouse plasma in the pg/mL range by
      gradient capillary liquid chromatography/tandem mass spectrometry.
AB  - Capillary high-performance liquid chromatography (HPLC; 300 microm i.d.) coupled
      to tandem mass spectrometry has been used to determine the concentration of 4
      hydroxytamoxifen in mouse plasma in the pg/mL range following the administration
      of Tamoxifen. A limit of quantification (LOQ) of 100 pg/mL was achieved using
      only 25 microL of plasma. The on-column sensitivity was determined to be 100 fg.
      The column performance was determined isocratically before and after the assay
      and showed only a 15% reduction in performance after 70 injections of plasma
      extract. No significant peak band broadening was observed due to the mass
      spectrometer interface using a standard TurboIonspray source.

PMID- 11223961
TI  - Chromatofocusing nonporous reversed-phase high-performance liquid
      chromatography/electrospray ionization time-of-flight mass spectrometry of
      proteins from human breast cancer whole cell lysates: a novel two-dimensional
      liquid chromatography/mass spectrometry method.
AB  - A novel two-dimensional two-column liquid chromatography/mass spectrometry
      (LC/MS) technique is described in this work, where chromatofocusing (CF) has been
      coupled to nonporous reversed-phase (NPS-RP) HPLC to separate proteins from human
      breast epithelial whole cell lysates. The liquid fractions from NPS-RP-HPLC are
      readily amenable to direct on-line analysis using electrospray ionization
      orthogonal acceleration time-of-flight mass spectrometry (ESI-TOFMS). A key
      advantage of this technique is that proteins can be 'peeled off' in the liquid
      phase from the CF column according to their isoelectric points (pI) in the first
      chromatographic separation dimension. The NPS-RP-HPLC column further separates
      these pI-focused fractions based upon protein hydrophobicity as the second
      chromatographic dimension. The third dimension involves on-line molecular weight
      determination using ESI-TOFMS. As a result, this method has the potential to be
      fully automated. In addition, a 2-D protein map of pI versus molecular weight is
      generated, which is analogous to a 2-D gel image. Thus, this technique may
      provide a means to study differential expression of proteins from whole cell
      lysates.

PMID- 11223963
TI  - Development of an analytical system for the simultaneous determination of
      anabolic macrocyclic lactones in aquatic environmental samples.
AB  - An analytical procedure that enables routine analysis for trace determination of
      six anabolic macrocyclic lactones (zearalenone, alpha- and beta-zearalenol,
      zearalanone, zeranol, and taleranol) in sewage treatment plant (STP) samples has
      been developed. The method uses solid-phase extraction, followed by high
      performance liquid chromatography with on-line tandem mass spectrometry using
      atmospheric pressure chemical ionization (LC/APCI-MS/MS). The extraction of these
      compounds from filtered water samples was performed off-line with C(18) solid
      phase cartridges. The detection was achieved by isocratic reversed-phase high
      performance liquid chromatography coupled with an heated nebulizer (HN) APCI
      interface operating in negative ion mode. Mean recovery of the analytes in STP
      effluent samples generally exceeded 81%. This method was used to determine the
      occurrence of target analytes in the aquatic environment. In the selected STP
      effluent samples, zearalenone and alpha-zearalenol were detected in the ng/L
      range.

PMID- 11223965
TI  - Collection, processing and cryopreservation of umbilical cord blood for unrelated
      transplantation.
AB  - Umbilical cord blood (UCB) transplantation is being used as an alternative source
      of hematopoietic stem cells for bone marrow reconstitution. Separation and
      processing of UCB samples in large numbers for storage in cord blood banks
      ideally needs to be partially automated. The aim of this study was to establish
      and standardize a method for unrelated cord blood banking as well as the
      biological characterization of the samples. Up to October 1999, a total of 938
      UCB units (mean volume 84.6 +/- 23.6 ml, nucleated cell (NC) count 0.90 +/- 0.37
      x 109, total CFU-GM 79 +/- 72 x 104, CD34+ cell count 2.46 +/- 2.72 x 106) had
      been collected. Twenty-three per cent of all UCB samples had a NC count below 0.4
      x 109 and were discarded. The initial bacterial contamination rate was reduced to
      less than 5% as a result of extensive training in collection procedures. Using a
      modification of a triple bag system and adding a solution of 6% hydroxyethyl
      starch, the UCB was separated by two centrifugation steps into three components:
      buffy coat, red cell and plasma fractions. The overall recoveries for NC, CFU-GM
      and CD34+ cells were 87.4 +/- 8.5%, 88.8 +/- 6.6% and 90.3 +/- 12.4%,
      respectively, in a mean final volume of 27 +/- 4.2 ml.

PMID- 11223967
TI  - Allogeneic hematopoietic transplantation of CD34+ selected cells from an HLA
      haplo-identical related donor. A long-term follow-up of 135 patients and a
      comparison of stem cell source between the bone marrow and the peripheral blood.
AB  - We studied the outcome of allogeneic transplants in 135 patients who received
      selected BM and/or PBSC CD34+ cells from HLA haplo-identical related donors.
      Donor engraftment was achieved in 108 of 128 evaluable transplants. Engraftment
      failure occurred more often in non-malignant than in malignant diseases (10 of 25
      vs 17 of 103, P = 0.010). The CD34+ cell dose was associated with the speed of
      neutrophil and platelet recovery, but the cell source was not. Acute GVHD (> or =
      grade II) developed in 21.0 +/- 3.7%. Chronic GVHD occurred more frequently in
      malignancies than in non-malignancies (44.1 +/- 7.6% vs 0.0%, P = 0.0075), and
      more in PBSC recipients than in BM recipients (53.6 +/- 9.4% vs 17.4 +/- 9.3%, P
      = 0.0054). Relapse rate was higher in high risk patients than in standard risk
      patients (78.7 +/- 7.1% vs 22.1 +/- 10.0%, P = 0.0001). Probabilities of disease
      free survival (DFS) were 14.2 +/- 3.5% in malignancies and 25.7 +/- 9.2% in non
      malignancies. Probabilities of DFS in standard and high risk patients were 39.4
      +/- 9.2% and 5.7 +/- 2.8% (P = 0.0001). A high incidence of graft failure,
      infection and relapse was observed and resulted in high mortality.

PMID- 11223966
TI  - Large-scale mobilization and isolation of CD34+ cells from normal donors.
AB  - We describe collection and purification of peripheral blood CD34+ cells from
      volunteer, normal donors and allogeneic stem cell donors. A total of 98 aphereses
      were performed on 68 volunteer donors using peripheral venous access. The mean
      number of nucleated cells collected was 4.6 x 10(10) which included 1.9 x 10(8)
      CD34+ cells corresponding to 2.7 x 10(6) CD34+ cells/kg. The number of CD34+
      cells collected did not differ between males and females but did correlate with
      the donor's weight and the total number of nucleated cells collected. The Nexell
      Isolex 300i cell separator was used to isolate CD34+ cells from 30 of the
      collections. A mean of 0.36% of the total cells was recovered and included 43 +/-
      18% of the CD34+ cells. CD34+ cells represented 85 +/- 11% of the recovered
      cells. The total number of CD34+ cells recovered was not influenced by the number
      of nucleated cells placed on the Isolex 300i. The percentage of CD34+ cells
      recovered was not related to the number of CD34+ cells placed on the Isolex 300i.
      The purity of the final product was influenced by the number of CD34+ cells but
      not the total number of nucleated cells. An additional 38 CD34+ cell isolations
      were performed on normal allogeneic stem cell donors with similar results. These
      observations further support the safety and feasibility of peripheral blood CD34+
      cell collection and purification.

PMID- 11223968
TI  - Using peripheral blood progenitor cells (PBPC) for transplantation in pediatric
      patients: a state-of-the-art review.
AB  - This paper presents a state-of-the-art review of using mobilized-peripheral blood
      progenitor cells (PBPC) for transplantation in children. Our own data and those
      from Medline searches and meeting reports, are analyzed and presented for the
      different sections that involve transplantation. Recommendations concerning the
      choice of mobilization regimens, venous access, priming of separator
      extracorporeal line, anticoagulation, and number of CD34+ cells to infuse for
      rapid engraftment are proposed. In the allogeneic setting, we analyze ethical and
      safety aspects of pediatric donor mobilization and collection. Data from the
      literature suggest that the use of cytokine-mobilized PBPC for allogeneic
      transplantation appears to be safe both for pediatric donors and patients leading
      a rapid hematopoietic engraftment with a similar incidence of acute graft-versus
      host disease (GVHD). The high incidence of chronic GVHD and its management emerge
      as the most concerning aspect in allogeneic PBPC transplantation.

PMID- 11223969
TI  - Predictive factors for long-term engraftment of autologous blood stem cells.
AB  - Data from 170 consecutive patients aged 19-66 years (median age 46 years) who
      underwent unmanipulated autologous blood stem cell transplant (ASCT) were
      analyzed to determine if total CD34+ cells/kg infused, CD34+ subsets (CD34+41+,
      CD34+90+, CD34+33-, CD34+38-, CD34+38-DR-), peripheral blood CD34+ cell (PBCD34+)
      count on first apheresis day, or various clinical factors were associated with
      low blood counts 6 months post ASCT. Thirty-four patients were excluded from
      analysis either because of death (n = 17) or re-induction chemotherapy prior to 6
      months post ASCT (n = 13), or because of lack of follow-up data (n = 4). Of the
      remaining 136 patients, 46% had low WBC ( < 4 x 10(9)/l), 41% low platelets (<150
      x 10(9)/l), and 34% low hemoglobin ( < 120 g/l) at a median of 6 months following
      ASCT. By Spearman's rank correlation, both the total CD34+ cell dose/kg and the
      PBCD34+ count correlated with 6 month blood counts better than any subset of
      CD34+ cells or any clinical factor. The PBCD34+ count was overall a stronger
      predictor of 6 month blood counts than was the total CD34+ cells/kg infused. Both
      factors retained their significance in multivariate analysis, controlling for
      clinical factors. In conclusion, subsets of CD34+ cells and clinical factors are
      inferior to the total CD34+ cell dose/kg and PBCD34+ count in predicting 6 month
      blood counts following ASCT.

PMID- 11223970
TI  - Alternative donor transplants for patients with advanced hematologic
      malignancies, conditioned with thiotepa, cyclophosphamide and antithymocyte
      globulin.
AB  - Preparative regimens without total body irradiation (TBI) have been reported for
      alternative donor hemopoietic stem cell transplants (HSCT). Between 7 September
      1994 and 7 June 1999 48 patients with advanced hematologic malignancies were
      conditioned with thiotepa (THIO) 15 mg/kg, cyclophosphamide (CY) 150 mg/kg and
      antithymocyte globulin (ATG). Donors were HLA mismatched family members (1-2
      antigens) (FAM) (n = 24, median age 31 years) or HLA matched unrelated donors
      (UD) (n = 24, median age 34 years). GVHD prophylaxis was cyclosporine and
      methotrexate. Stem cell source was peripheral blood (n = 8) or bone marrow (n =
      40). Hematologic recovery was seen in 42/46 (91%) evaluable patients and complete
      chimerism in 31/37 patients (85%). Acute GVHD grades III-IV were seen in 10/46
      patients surviving 10 days (21%) and extensive chronic GVHD in 2/36 patients
      surviving 100 days (5%). Twenty-six patients died (54%), eight of recurrent
      disease (17%) and 18 of transplant-related complications (37%): main causes of
      TRM were GVHD (15%), infections (15%) and graft failure (4%). Twenty-two patients
      (46%) survive with a median follow-up of 877 days (287-1840). The actuarial 3
      year survival is 49% for FAM and 42% for UD transplants. Results obtained with
      this regimen in unrelated grafts for advanced CML (n = 15) were not significantly
      different when compared to 21 concurrent UD grafts for advanced CML prepared with
      CY-TBI. In conclusion, the combination of THIO-CY-ATG allows engraftment of
      alternative donor hemopoietic stem cells. Results are similar when using
      unrelated matched donors or partially mismatched family donors, and not
      significantly different when compared to patients conditioned with CY-TBI.

PMID- 11223971
TI  - Predicting the severity of intestinal graft-versus-host disease from leukotriene
      B4 levels after bone marrow transplantation.
AB  - Intestinal graft-versus-host disease (GVHD) produces clinical manifestations and
      histological changes resembling those of ulcerative colitis and has been treated
      with drugs which are used for ulcerative colitis. These two conditions also
      resemble each other with respect to changes of cytokines. Accordingly, we
      investigated whether the level of leukotriene B4, a risk factor for ulcerative
      colitis, was also a risk factor or prognostic indicator for intestinal GVHD. The
      pre-conditioning leukotriene B4 level was significantly related to the grade of
      intestinal GVHD in 42 patients (P < 0.01). Compared with patients who did not
      develop severe intestinal GVHD after bone marrow transplantation, those who did
      had significantly higher interleukin-2 and interferon-gamma levels during the
      aplastic phase (P <0.01), followed by higher tumor necrosis factor-alpha levels
      during the recovery phase (P < 0.0001), with significant elevation of tumor
      necrosis factor-alpha and interferon-gamma occurring in association with
      exacerbations of intestinal GVHD (P < 0.001). These findings suggest a similarity
      between the pathogenesis of ulcerative colitis and intestinal GVHD and raise the
      possibility that leukotriene B4 may be a useful prognostic indicator for
      intestinal GVHD.

PMID- 11223972
TI  - Contribution of TNF-alpha and IL-10 gene polymorphisms to graft-versus-host
      disease following allo-hematopoietic stem cell transplantation.
AB  - Some cytokines are believed to play a role in the development of acute and
      chronic GVHD after allo-hematopoietic stem cell transplantation. It has been
      reported that TNF-alpha and IL-10 gene polymorphisms are associated with the
      production of those cytokines and the development of graft failure after organ
      transplantation and systemic lupus erythematosus. We examined whether TNF-alpha
      and IL-10 gene polymorphisms affect the severity of acute GVHD (aGVHD) and
      chronic GVHD (cGVHD). Sixty-two and 54 patients were available for the analysis
      of aGVHD and cGVHD, respectively. We analyzed the gene polymorphisms derived from
      pre- and post-transplant blood cells. Donor-derived TNF2 allele (A) was more
      frequently detected in patients with aGVHD III/IV than those aGVHD 0-II (2/6 vs
      2/56) (P = 0.04). The donors of the patients with cGVHD more frequently possessed
      a greater number of alleles (allele 13 or more which contain 26 or more CA
      repeats) in IL-10.G than those without (13/26 vs 5/28) (P = 0.02), and the
      patients with cGVHD had more CA repeats in donor-derived IL-10.G than those
      without (mean = 25.2 vs 23.4) (P = 0.01). Donor-derived TNF-308 and IL-10.G
      alleles may contribute to severe aGVHD and cGVHD, respectively, and will help us
      distinguish those patients at high risk for GVHD.

PMID- 11223973
TI  - Different immune reconstitution in multiple myeloma, chronic myeloid leukemia and
      acute myeloid leukemia patients after allogeneic transplantation of peripheral
      blood stem cells.
AB  - In this study we compared the lymphocyte reconstitution in 13 multiple myeloma
      (MM), nine acute myeloid leukemia (AML) and 10 chronic myeloid leukemia (CML)
      patients after allogeneic G-CSF-mobilized PBSC transplantation from HLA-identical
      siblings. Conditioning regimens included standard total body irradiation +
      cyclophosphamide (CY), or busulphan + CY, whereas VP-16 was added in patients
      with advanced disease. Overall comparable numbers of mononuclear cells, CD34+
      cells and CD3+ T cells were infused in each group. A significantly higher CD3+ T
      cell number was observed in MM and AML than in CML patients 1 month after
      transplant. However, MM patients showed a faster and better recovery of CD4+ T
      cells than both AML and CML patients at 3 months (P = 0.01 and P = 0.01,
      respectively) and 12 months (P = 0.01 vs AML, while P = NS vs CML) after
      transplant, and had a CD4:CD8 ratio > 1 with a median CD4+ T cell value >
      400/microl 1 year after transplant. Development of acute graft-versus-host
      disease (GVHD) did not affect CD4:CD8 ratios but patients who experienced acute
      GVHD > grade I had lower CD4+ and CD8+ T cell numbers at all time points.
      However, after excluding patients with GVHD > grade I, MM patients still showed a
      significantly higher CD4+ T cell value than patients with myeloproliferative
      diseases 1 year after transplant. These findings suggest that although allogeneic
      PBSC transplantation induces rapid immune reconstitution, different kinetics may
      occur among patients with hematological malignancies. In particular, the rapid
      reconstitution of CD4+ T cells in MM patients may contribute to the low
      transplant-related mortality achieved in this disease.

PMID- 11223975
TI  - Epstein-Barr virus-associated T cell lymphoproliferative disorder following
      autologous blood stem cell transplantation for relapsed Hodgkin's disease.
AB  - Post-transplant lymphoproliferative disorders (PTLD) of T cell type are a rare
      complication of solid organ and allogeneic hematopoietic cell transplantation
      (HCT), and usually are not associated with Epstein-Barr virus (EBV) infection.
      EBV-associated T cell PTLD has not been reported to occur after autologous HCT.
      We report an unusual case of T cell lymphoproliferation after autologous blood
      stem cell transplantation (ABSCT). A patient with relapsed Hodgkin's disease
      developed abdominal lymphadenopathy followed by atypical CD8+ lymphocytosis in
      the peripheral blood 30 months following ABSCT. DNA studies of the atypical
      lymphocytes demonstrated rearrangements of the T cell receptor beta gene and a
      clonal proliferation of EBV.

PMID- 11223974
TI  - Outcome and clinical course of 100 patients with adenovirus infection following
      bone marrow transplantation.
AB  - We conducted a retrospective review of the clinical features and outcome of
      adenovirus infection in 572 consecutive patients transplanted in a single centre
      over a 10 year period. One hundred patients (17%) had a total of 105 episodes of
      adenovirus infection diagnosed at a median of 18 days post transplant (range 2
      150 days). The incidence was higher in children than adults (21% vs 9%, P <
      0.001) and in unrelated donor vs matched sibling donor transplants (26% vs 9%, P
      < 0.001). Diarrhoea and fever were the most common presenting features.
      Reflecting these symptoms, the most common site of isolation was the stool.
      Serotypes 1, 2 and 7 were the most frequently seen (total of 41/68 or 60% of
      evaluable cases). In six patients (6%) adenovirus infection was the direct cause
      of death occurring at a median of 72 days post transplant (range 18-365 days).
      Five of these six patients had pulmonary involvement and four had associated
      graft-versus-host disease (GVHD). Three further patients were considered to have
      severe adenoviral disease (total incidence 9%). Isolation of virus from multiple
      sites correlated with a poor outcome (P < 0.001). Comorbid viral infection was
      common in this group with 50% of all patients having other viruses isolated
      (predominantly polyoma virus and cytomegalovirus). We conclude that adenovirus is
      commonly isolated after bone marrow transplant and is a cause of significant
      morbidity but was a rare cause of mortality (6/572 = 1%) in our patient group as
      a whole. The relative infrequency of severe infection will make it difficult for
      the transplant physician to decide which patients should receive experimental
      antiviral drugs such as ribavirin and cidofovir or immunomodulatory therapy with
      donor white cell infusions.

PMID- 11223976
TI  - Cryofibrinogenemia and skin necrosis in a patient with diffuse large cell
      lymphoma after high-dose chemotherapy and autologous stem cell transplantation.
AB  - A 34-year-old woman with diffuse mediastinal B cell large cell lymphoma presented
      60 days after high-dose chemotherapy and autologous stem cell transplantation,
      and post-transplant immunotherapy with interleukin-2, with skin necrosis in the
      ears and extremities. Extensive work-up revealed the presence of
      cryofibrinogenemia and associated thrombotic vasculopathy. The patient was
      successfully treated with corticosteroids and therapeutic plasma exchange.
      However, she had recurrence of large cell lymphoma a few weeks later and died of
      progressive disease. Cryfibrinogenemia and skin necrosis may have occurred
      secondary to the imminent relapse, or as a rare complication of high-dose
      chemotherapy or treatment with interleukin-2.

PMID- 11223977
TI  - Cytomegalovirus pneumonitis, activated prothrombin time prolongation and subacute
      thyroiditis after unrelated allogeneic bone marrow transplantation.
AB  - A 22-year-old female with acute myeloid leukemia (AML) in complete remission
      received a conditioning regimen containing antithymocyte globulin for an
      unrelated bone marrow transplant (BMT). After BMT, the patient suffered from
      cytomegalovirus (CMV) pneumonitis with markedly high levels of CMV antigenemia,
      activated prothrombin time (APTT) prolongation, and subacute thyroiditis.
      Recovery of CD4+ cells was delayed as long as 1 year after BMT. An association
      between these three episodes and viral infection due to the delayed recovery of
      CD4+ cells is suggested.

PMID- 11223978
TI  - Allogeneic stem cell transplantation in a patient with refractory Burkitt's
      lymphoma using non-myeloablative conditioning regimen.
AB  - We have performed an allogeneic stem cell transplant in an 18-year-old male
      patient who had Burkitt's lymphoma. The patient had disease which was refractory
      to conventional intensive chemotherapy and radiation therapy. High-dose
      chemotherapy with autologous stem cell rescue was given but the patient relapsed
      within 2 months after transplantation. He was then treated with allogeneic stem
      cell transplantation using a fludarabine, busulfan and anti-thymocyte globulin
      based conditioning regimen. His GVHD prophylaxis included mycophenolate and
      tacrolimus. The patient had engraftment within 14 days. Investigation by FISH
      showed more than 95% of his peripheral blood nucleated cells to be of donor
      origin since day +14. He is now alive and well and remains disease-free 6-months
      after the transplant. A graft-versus-lymphoma effect is thought to be one of the
      factors contributing to his remission.

PMID- 11223979
TI  - Radiation myelitis following allogeneic stem cell transplantation and
      consolidation radiotherapy for non-Hodgkin's lymphoma.
AB  - Myelitis is a rare but well documented complication of therapeutic radiation
      exposure to the spinal cord and is characterized by delayed development of
      paresthesias, sensory changes and, in severe cases, progressive paresis and
      paralysis. Although accepted radiation tolerance limits for the spinal cord have
      successfully limited the incidence of this problem (45-50 Gy, in daily 1.8-2 Gy
      fractions), aggressive systemic therapy may render patients more susceptible to
      radiation-related neurotoxicity. We describe the case of a 38-year-old man with
      refractory non-Hodgkin's lymphoma who underwent matched sibling peripheral blood
      stem cell transplant following a conditioning regimen of cyclophosphamide (60
      mg/kg x 2) and total body irradiation (120 cGy x 11). This was followed by
      delivery of 30.6 Gy involved-field radiation at 1.8 Gy/day to the mediastinum and
      left supraclavicular fossa for bulky residual tumor. Although maximum cumulative
      radiation dose to the spinal cord was less than 45 Gy, the patient subsequently
      developed progressive lower extremity weakness and MRI abnormalities of the
      spinal cord limited to the radiation field. This represents the second report in
      the literature of this unexpected complication, prompting a need to re-examine
      current guidelines for radiotherapy in the context of high-dose systemic
      treatment.

PMID- 11223980
TI  - Reduced-intensity allogeneic stem cell transplantation as salvage treatment for
      patients with indolent lymphoma or CLL after failure of autologous SCT.

PMID- 11223981
TI  - Safety profile of mycophenolate mofetil.

PMID- 11223985
TI  - Exploring vascular heterogeneity for gene therapy targeting.

PMID- 11223986
TI  - A novel doxycycline inducible autoregulatory plasmid which displays "on"/"off"
      regulation suited to gene therapy applications.
AB  - The development of transcriptionally controlled systems which function in
      eukaryotic cells are important for achieving regulated gene expression in gene
      therapy. In this study we combined the components of the tetracycline-inducible
      system in self-contained retroviral and plasmid vectors. Regulated reporter gene
      expression from the autoregulatory plasmid pGTRTL in response to doxycycline
      (Dox) induction surpasses the expression observed from other self-contained
      retroviral and plasmid vectors. Induction kinetics and expression levels of
      luciferase and the therapeutic molecule, truncated soluble complement receptor 1
      (sCR1) were characterised in a mouse fibroblast and a human neuroblastoma cell
      line. The regulatory characteristics of the plasmids were shown to be optimal for
      gene therapy applications, as there was a rapid reduction in expression levels
      following removal of Dox. Co-transfection of cells with an autoregulatory plasmid
      and a Dox inducible enhanced green fluorescent protein (EGFP) plasmid
      demonstrated the feasibility of using this plasmid combination to achieve
      parallel regulation of two genes of interest in a single cell under the control
      of Dox. These novel autoregulatory plasmids display the requirements for gene
      therapy applications in chronic conditions which are remitting/relapsing such as
      rheumatoid arthritis or multiple sclerosis, where novel protein therapeutics and
      combination therapies are needed. Gene Therapy (2000) 7, 2061-2070.

PMID- 11223988
TI  - Persistent, antigen-specific, therapeutic antitumor immunity by dendritic cells
      genetically modified with an adenoviral vector to express a model tumor antigen.
AB  - Dendritic cells (DC) are potent antigen-presenting cells that play a critical
      role in the initiation of cellular immune responses. Using a BALB/c syngeneic
      colon carcinoma cell line expressing a model tumor antigen beta-galactosidase
      (betagal), we previously reported (Song et al, J Exp Med 1997; 186: 1247-1256)
      that immunization of mice with a single injection of DCs genetically modified
      with an adenovirus vector expressing betagal confers potent protection against a
      lethal intravenous tumor challenge, as well as suppression of pre-established
      lung tumors, resulting in a significant survival advantage. In the present study,
      we have addressed the question: how long does the memory of tumor antigen-
      specific immunity persists after DC priming in vivo using this genetically
      modified DC-based cancer vaccination strategy? To accomplish this, two groups of
      mice were evaluated: (1) mice surviving >400 days following protection from an
      initial intravenous tumor challenge after immunization with DC genetically
      modified to express betagal; and (2) mice surviving >300 days that had previously
      demonstrated regression of pre-established lung tumors after treatment with DC
      immunization. By analyzing the antigen-specific cytotoxic T lymphocyte response
      and challenging these long-term survival mice with a second subcutaneous tumor
      administration, the data demonstrate that a single administration of DC
      genetically modified to express a model antigen induces long-lasting, antigen
      specific antitumor immunity in both naive and tumor-bearing hosts, observations
      that have important implications in the development of genetically modified DC
      based antitumor vaccination strategies. Gene Therapy (2000) 7, 2080-2086.

PMID- 11223987
TI  - Combination therapy of malignant glioma cells with 2-5A-antisense telomerase RNA
      and recombinant adenovirus p53.
AB  - Malignant gliomas of astrocytic origin have commonly expressed several features
      such as alterations in the tumor-suppressor gene p53 or p16 or the acquisition of
      telomerase activity, which are distinctive from astrocytes. Therefore,
      restoration of the tumor-suppressor gene or telomerase inhibition is expected to
      provide a cure for malignant gliomas. We have recently demonstrated that the
      treatment with a 19-mer antisense oligonucleotide against human telomerase RNA
      linked to a 2',5'-oligoadenylate (2-5A-anti-hTR) inhibited the growth of
      malignant glioma cells. From a therapeutic point of view, it is very important to
      investigate the antitumor efficacy of 2-5A-anti-hTR combined with the restoration
      of p53 or p16 gene. In this study, we evaluated the antitumor effect of 2-5A-anti
      hTR in combination with recombinant adenoviruses bearing p53, its associated
      p21WAF1/CIP1, or p16CDKN2 gene (Ad5CMV-p53, Ad5CMV-p21, or Ad5CMV-p16) against
      malignant glioma cells in vitro and in vivo. Five malignant glioma cell lines
      expressing the mutant p53 gene (A172, GB-1, T98G, U251-MG and U373-MG) were more
      sensitive to the combination of 2-5A-anti-hTR and Ad5CMV-p53 than to other
      combinations. The additive effect of the combination therapy was due to induction
      of caspase-dependent apoptosis and cell growth arrest. Furthermore, the 2-5A-anti
      hTR treatment when combined with Ad5CMV-p53 showed greater efficacy against
      subcutaneous U251-MG tumors in nude mice. In contrast, U87-MG cells expressing
      the wild-type p53 gene were insensitive to Ad5CMV-p53, although the treatment
      with 2-5A-anti-hTR was significantly effective. These results indicate that
      combining 2-5A-anti-hTR with Ad5CMV-p53 has the most therapeutic potential for
      malignant gliomas with mutant p53. For tumors exhibiting wild-type p53, it may be
      useful to treat with 2-5A-anti-hTR. Gene Therapy (2000) 7, 2071-2079.

PMID- 11223989
TI  - Direct intra-cardiomuscular transfer of beta2-adrenergic receptor gene augments
      cardiac output in cardiomyopathic hamsters.
AB  - In chronic heart failure, down-regulation of beta-adrenergic receptor (beta-AR)
      occurs in cardiomyocytes, resulting in low catecholamine response and impaired
      cardiac function. To correct the irregularity in the beta-AR system, beta-AR gene
      was transduced in vivo into failing cardiomyocytes. The Epstein-Barr virus (EBV)
      based plasmid vector carrying human beta2-AR gene was injected into the left
      ventricular muscle of Bio14.6 cardiomyopathic hamsters whose beta-AR is down
      regulated in the cardiomyocytes. The echocardiographic examinations revealed that
      stroke volume (SV) and cardiac output (CO) were significantly elevated at 2 to 4
      days after the beta2-AR gene transfer. Systemic loading of isoproterenol
      increased the cardiac parameters more significantly on day 2 to day 7, indicating
      that the adrenergic response was augmented by the genetic transduction. The same
      procedure did not affect the cardiac function of normal hamsters.
      Immunohistochemical examinations demonstrated human beta2-AR expression in
      failing cardiomyocytes transduced with the gene. RT-PCR analysis detected mRNA
      for the transgene in the heart but not in the liver, spleen, or kidney. The
      procedures may provide a feasible strategy for gene therapy of severe heart
      failure. Gene Therapy (2000) 7, 2087-2093.

PMID- 11223990
TI  - Demyelination but no cognitive, motor or behavioral deficits after adenovirus
      mediated gene transfer into the brain.
AB  - Adenovirus-mediated gene transfer of interferon gamma (AdIFN) elicits rejection
      of intracerebral Lewis lung carcinoma. In this system, gene transfer into brain
      parenchymal cells is both necessary and sufficient to generate the antitumor
      response. Despite persistent parenchymal inflammation and demyelination, wild
      type mice injected intracerebrally with either AdIFN or beta-galactosidase
      adenovirus (AdBGAL) perform as well as non-injected animals in behavioral,
      memory, and motor tests. Both AdIFN and AdBGAL elicit demyelination whose
      incidence rises sharply when the lowest effective dose of AdIFN is exceeded.
      Therefore, transfer of interferon gamma into brain parenchyma does not seem to
      elicit detectable cognitive, behavioral or motor deficits. Furthermore, gene
      transfer into the brain, by adenoviral vectors currently in clinical trials, is
      associated with a narrow therapeutic window where the incidence of demyelination
      rises sharply soon after the effective dose is achieved. Gene Therapy (2000) 7,
      2094-2098.

PMID- 11223991
TI  - Degradable polymeric carrier for the delivery of IL-10 plasmid DNA to prevent
      autoimmune insulitis of NOD mice.
AB  - Recently, we have reported that biodegradable poly [alpha-(4-aminobutyl)-L
      glycolic acid] (PAGA) can condense and protect plasmid DNA from DNase I. In this
      study, we investigated whether the systemic administration of pCAGGS mouse IL-10
      (mIL-10) expression plasmid complexed with PAGA can reduce the development of
      insulitis in non-obese diabetic (NOD) mice. PAGA/mIL-10 plasmid complexes were
      stable for more than 60 min, but the naked DNA was destroyed within 10 min by
      DNase I. The PAGA/DNA complexes were injected into the tail vein of 3-week-old
      NOD mice. Serum mIL-10 level peaked at 5 days after injection, and could be
      detected for more than 9 weeks. The prevalence of severe insulitis on 12-week-old
      NOD mice was markedly reduced by the intravenous injection of PAGA/DNA complex
      (15.7%) compared with that of naked DNA injection (34.5%) and non-treated
      controls (90.9%). In conclusion, systemic administration of pCAGGS mIL-10
      plasmid/PAGA complexes can reduce the severity of insulitis in NOD mice. This
      study shows that the PAGA/DNA complex has the potential for the prevention of
      autoimmune diabetes mellitus. Gene Therapy (2000) 7, 2099-2104.

PMID- 11223992
TI  - Plasmid DNA adsorbed onto cationic microparticles mediates target gene expression
      and antigen presentation by dendritic cells.
AB  - Dendritic cells (DC) play a key role in antigen presentation and activation of
      specific immunity. Much current research focuses on harnessing the potency of DC
      for vaccines, gene therapy, and cancer immunotherapy applications. However, DC
      are not readily transfected in vitro by traditional nonviral techniques. A novel
      DNA vaccine formulation was used to determine if DC are transfected in vitro. The
      formulation consists of plasmid DNA adsorbed on to cationic microparticles
      composed of the biodegradable polymer polylactide-co-glycolide (PLG) and the
      cationic surfactant, cetyltrimethylammonium bromide (CTAB). Using preparations of
      fluorescent-labeled plasmid DNA formulated on PLG-CTAB microparticles to study
      internalization by macrophages and dendritic cells in vitro and in vivo, we found
      that most, but not all, of the fluorescence was concentrated in endosomal
      compartments. Furthermore, uptake of plasmid DNA encoding HIV p55 gag adsorbed to
      PLG-CTAB microparticles by murine bone marrow-derived dendritic cells resulted in
      target gene expression, as detected by RT-PCR. The antigen was subsequently
      processed and presented, resulting in stimulation of an H-2kd-restricted, gag
      specific T cell hybridoma. Activation of the hybridoma, detected by IL-2
      production, was dose-dependent in the range of 0.1-20 microg DNA (10-2000 microg
      PLG) and was sustained up to 5 days after transfection. Thus, adsorption of
      plasmid DNA on PLG-CTAB microparticles provides a potentially useful nonviral
      approach for in vitro transfection of dendritic cells. Gene Therapy (2000) 7,
      2105-2112.

PMID- 11223993
TI  - Enhancement of antitumor immunity against B16 melanoma tumor using genetically
      modified dendritic cells to produce cytokines.
AB  - Dendritic cells (DC) that have been genetically modified to express cytokine
      genes may be novel tools for inducing antitumor immune responses. In the present
      study, the pMX retroviral vector was modified to express the mouse IL-2 (mIL
      2pMX) and mouse IL-12 (mIL-12pMX) genes. Supernatants from 293 cells transfected
      with pMX retroviral vectors were harvested and used to transduce mouse lin- bone
      marrow (BM) progenitor cells. After 48 h co-culture with pseudotype retrovirus,
      BM cells were cultured for 12 days in the presence of mGM-CSF, mSCF and mTNF
      alpha to obtain a DC-enriched fraction. Flow cytometric analysis showed that GFP
      protein expression in these cultures was 20-40% and that 40-50% of the cultured
      BM cells were positive for the DC marker, DEC205. About 60% of cells sorted for
      DEC205 also expressed GFP. The supernatants of DC-mIL-2 and DC-mIL-12 cultured
      for 48 h contained 5.2 +/- 0.15 and 33.9 +/- 2.6 ng cytokine protein per
      milliliter, respectively. Intratumoral injection of DC-mIL-2 or DC-mIL-12 on days
      8 and 15 after the intradermal injection of 1 x 105 B16F10 cells, resulted in a
      significant reduction in tumor size by day 21, as compared with mice treated with
      unmodified DC or DC-GFP. Longer term analysis as assessed at day 42 revealed that
      B16 tumor-bearing mice treated with cytokine gene-modified DC survived
      significantly longer than mice from other groups. Spleen cells obtained from DC
      treated mice were specifically sensitized for the generation of CTL by subsequent
      restimulation with gene-modified DC. These results suggested that DC genetically
      modified to express IL-2 or IL-12 can induce potent antitumor responses against
      well-established, poorly immunogenic B16F10 tumors. Gene Therapy (2000) 7, 2113
      2121.

PMID- 11223994
TI  - Virus-like gene transfer into cells mediated by polyoma virus pseudocapsids.
AB  - Mouse polyoma virus-like particles (or pseudocapsids) are composed solely of
      recombinant viral coat protein. They can interact with DNA and transport it to
      cells, resulting in gene expression both in tissue culture and in mice. We
      demonstrate that DNA transfer in vitro depends on partial packaging of DNA within
      the virus-like capsid. Cell surface sialic acid residues and an intact
      microtubule network, required for viral infectivity, are also necessary for
      pseudocapsid-mediated gene expression from heterologous DNA. Thus, gene delivery
      in this system requires pathways utilised by polyoma virions, rather than
      proceeding via the 'nonspecific' endosomal route typical of nonviral systems such
      as liposomes or calcium phosphate precipitates. Despite the fact that all cells
      appear to internalise pseudocapsid/DNA complexes, only a proportion show
      productive gene delivery. Bulk internalisation of complexes is dependent on actin
      fibres, but not cell surface sialic acid or microtubules, indicating that a
      second transport pathway exists for pseudocapsids which is nonproductive for gene
      transfer. The model suggested by these data demonstrates the virus-like
      properties of the pseudocapsid system, and provides a basis for further
      development to produce a highly effective gene delivery vehicle. Gene Therapy
      (2000) 7, 2122-2131.

PMID- 11223995
TI  - Adenoviral vector design for high-level transgene expression in primitive human
      hematopoietic progenitors.
AB  - Adenoviral vector-mediated transient gene expression can provide new
      possibilities for ex vivo manipulation of quiescent hematopoietic stem cells
      (HSC). In order to define a suitable expression cassette for high levels of
      transgene expression in HSCs, we have studied the level of transgene expression
      in human CD34+CD38- cells using adenoviral vectors with various gene expression
      cassettes encoding the enhanced green fluorescence protein (EGFP) gene. CD34+
      hematopoietic cells were cultured in serum-free medium with megakaryocyte growth
      and development factor (MGDF) alone for supporting the survival of primitive
      progenitors or with MGDF, c-kit ligand (KL) and flt3 ligand (FL) for inducing
      proliferation of primitive progenitors. With all the vectors tested, higher
      percentages of EGFP expressing cells were found in CD34+CD38- cells than those in
      CD34+CD38high cells from all donors tested. The phosphoglycerate kinase (PGK)-1
      promoter was found to allow higher levels of EGFP expression than the human
      cytomegalovirus (HCMV) promoter in CD34+CD38- cells. Replacing the SV40
      polyadenylation signal with the human beta-globin gene IVS2 and polyadenylation
      signal in the expression cassette (Ad5xPGK-EGFP-beta-globin) enhanced the level
      of EGFP expression markedly further. These results provide a guideline for the
      development of adenoviral vectors for gene expression in human primitive
      hematopoietic progenitor cells. Gene Therapy (2000) 7, 2132-2138.

PMID- 11223996
TI  - Making prevention and management of hypertension work.

PMID- 11223997
TI  - Franz Volhard and Theodor Fahr: achievements and controversies in their research
      in renal disease and hypertension.
AB  - The clinician, Franz Volhard, and the pathologist, Theodor Fahr, worked closely
      together in Mannheim from 1909 until 1915 and introduced a novel classification
      of renal diseases. In the monograph entitled 'Die Bright'sche Nierenkrankheit,
      Klinik, Pathologie und Atlas' (1914) they differentiated between degenerative
      (nephroses), inflammatory (nephritides) and arteriosclerotic (scleroses)
      diseases. Nephrosclerosis was divided into the benign and malignant form, of
      which the latter stood the test of time as a new disease entity. Fahr further
      divided benign nephrosclerosis into the compensated and decompensated form-
      depending on the presence or absence of glomerular injury. In the pathogenesis of
      malignant nephrosclerosis, Volhard stressed the decisive role of severe blood
      pressure elevation, while Fahr postulated an inflammatory mechanism, a concept
      later confirmed by Adalbert Bohle for at least a minority of patients. A very far
      reaching concept of Franz Volhard was his idea that pale (renal) hypertension
      results from a pressor substance released from ischaemic kidney(s) contributing-
      via a vicious circle--to a further rise in blood pressure with subsequent
      renovascular injury and aggravation of hypertension. This hypothesis was
      supported in 1930 by initial experiments of his collaborator, Hartwich
      (demonstrating in dogs a mild rise in blood pressure after ligation of branches
      of the renal artery) and definitively proven by Goldblatt (1934) in dogs by
      induction of severe and persistent hypertension after clamping of both renal
      arteries. The consequent detection of the renin angiotensin system was the final
      confirmation of Volhard's postulated renal pressor substance. In the pathogenesis
      of red (essential) hypertension, Volhard stressed the role of hereditary factors,
      age, obesity and potentially of severe alcoholism. He emphasised a premature
      reduction of vascular distensibility (due to elastosis of the prearterioles), a
      high cardiac output as well as a dampening of baroceptor function. Additionally,
      Volhard made crucial advances in cardiology and pneumology. Journal of Human
      Hypertension (2001) 15, 5-16

PMID- 11223998
TI  - Why is plasma renin activity lower in populations of African origin?
AB  - Plasma renin activity is significantly lower in black people compared with whites
      independent of age and blood pressure status. The lower PRA appears to be due to
      a reduction in the rate of secretion of renin but the exact mechanistic events
      underlying such differences in renin release between blacks and whites are still
      not fully understood. Nevertheless, given the paramount importance of the renin
      angiotensin system in the control of sodium balance, a most likely explanation is
      that the lower renin is a consequence of differences in renal sodium handling
      between blacks and whites. The lower PRA does not reflect differences in dietary
      sodium intake but the evidence available suggests that the low PRA could be part
      of the corrective mechanisms designed to maintain sodium balance in the presence
      of an increased tendency for sodium retention in black people. While it is
      possible that several factors may contribute to the reduced PRA, more recent
      investigation at the molecular level suggests that the lower PRA may arise from
      gene variation in the renal epithelial sodium channel. The functional
      significance of the lower PRA in relation to the different pattern of
      cardiovascular and renal disease between blacks and whites remains unclear.
      Moreover, direct investigations of pre-treatment renin status in hypertensive
      blacks in relation to blood pressure response have demonstrated that the pre
      treatment PRA is not a good index of subsequent blood pressure response to
      pharmacological treatment. Nevertheless, the blood pressure reduction to short
      term sodium restriction is greater in blacks compared with whites and, in the
      black subjects, the greater reduction in blood pressure to sodium restriction
      appears to be related, at least in part, to the decreased responsiveness of the
      renin-angiotensin system. Journal of Human Hypertension (2001) 15, 17-25

PMID- 11223999
TI  - Assessing hypertension management in the community: trends of prevalence,
      detection, treatment, and control of hypertension in the MONICA Project, Augsburg
      1984-1995.
AB  - OBJECTIVE: To assess trends in prevalence and detection, treatment and control of
      hypertension in a German population between 1984 and 1995. SETTING AND
      PARTICIPANTS: Independent random samples of the population were examined in cross
      sectional surveys with identical methods in 1984/85 (age range 25 to 64 years, n
      = 4022 participants), 1989/90 (age range 25 to 74 years, n = 4940) and 1994/95
      (age range 25 to 74 years, n = 4856). MAIN OUTCOME MEASURES: Prevalence of
      hypertension and proportions of hypertensives detected, treated and controlled.
      Hypertension was defined as blood pressure above 140/90 mm Hg or taking
      antihypertensive medication. RESULTS: The prevalence of hypertension did not
      change significantly over the 10 years (25--64 years, age-standardised 1984/85:
      37.8% in men and 24.6% in women; 1994/95: 39.3% and 24.8%, respectively). Rates
      of detection, treatment and control of hypertension did not change much either.
      Of all hypertensives in 1994/95, 54% were detected in men and 64% in women, the
      treatment rates were 23% and 32%, and the proportions of those with controlled
      hypertension (below 140/90 mm Hg with treatment) were as low as 7% and 13%,
      respectively. Rates were higher in the older age groups, however, control rates
      never exceeded 20% at any age. CONCLUSIONS: Despite considerable changes in the
      pharmacological treatment of hypertension there was a disappointing stagnation
      with regard to the management of this important risk factor in the community. The
      reasons for this unfavourable trend need clarification and appropriate public
      health action. Journal of Human Hypertension (2001) 15, 27-36

PMID- 11224000
TI  - Increased membraneous calcium concentrations in primary hypertension: a causal
      link to pathogenesis?
AB  - BACKGROUND: Disturbance in calcium metabolism has been suggested in the
      pathogenesis of hypertension, however, membrane calcium content in humans has not
      been studied in detail yet in primary hypertension. We compared plasma,
      intracellular and membrane calcium concentrations in erythrocytes of patients
      with essential hypertension and in healthy, normotensive control subjects to
      determine a possible alteration of membrane calcium in primary hypertension.
      SUBJECTS AND METHODS: Thirty-four never treated patients with essential
      hypertension were included and 34 healthy, age- and sex-matched volunteers served
      as controls. Atomic absorption spectroscopy was used for measurement of
      intracellular and membrane calcium content in erythrocytes and plasmalemmal
      preparations. RESULTS: Plasma and intracellular Ca(++) concentrations were not
      significantly different between hypertensives and controls (plasma: 2.59 +/- 0.18
      vs2.50 +/- 0.16 mmol/l, intracellular: 1.89 +/- 0.20 mmol/l vs 1.97 +/- 0.24
      mmol/l, NS resp., mean +/- s.e.m.). However, membrane calcium content was
      significantly higher in hypertensive patients compared to control subjects (2.38
      +/- 0.28 micromol/g membraneous protein vs0.86 +/- 0.32 micromol/g membrane
      protein, P < 0.01). Membrane calcium content was correlated to mean arterial
      blood pressure (r = 0.59, P < 0.01). CONCLUSION: Membrane calcium content is
      significantly increased in patients with untreated primary hypertension and
      correlates to blood pressure levels. This data suggest, that an membrane
      mechanism may contribute to alterations in calcium metabolism and to the
      pathogenesis of primary hypertension.

PMID- 11224001
TI  - Relationship between short-term and long-term blood pressure variabilities in
      essential hypertensives.
AB  - This study was designed to analyse the relationship between the different blood
      pressure (BP) variabilities obtained in a non-invasive way and to determine the
      potential contribution of aging, severity of hypertension and increased
      ventricular mass to these different BP variabilities. Two hundred and six
      hypertensive patients underwent a 24-h ambulatory BP measurement (ABPM) as well
      as a photoplethysmographic BP recording and a standard echocardiography.
      Nocturnal BP fall and standard deviations of hourly mean BP levels as well as
      post-prandial fall in BP were calculated from the 24-h ABPM and were considered
      as indexes of long-term variability. Baroreflex sensitivity (BRS) and spectral
      powers of systolic BP, diastolic BP and heart rate (HR) over the low frequency
      band (LF: 0.05--0.14 Hz) were obtained from photoplethysmographic recording and
      were used as indexes of short-term variability. Short-term variability indexes
      were shown to be significantly related to those of long-term variability. A
      decrease in LF spectral powers was associated with a particular profile
      characterised by an attenuation of nocturnal BP fall, an increase of daytime BP
      standard deviations, an increase in post-prandial BP fall, a decrease in BRS and
      to a lesser extent, a diminution in night-time HR standard deviation. Moreover, a
      negative significant relationship was found between standard deviation of daytime
      systolic BP and both night systolic BP fall and BRS. Age and nocturnal BP level
      were associated with all BP variability disorders, whereas left ventricular
      hypertrophy was associated only with a decrease in LF spectral powers and in
      night BP fall, and an increase in standard deviation of daytime BP. Finally, LF
      spectral power of SBP was identified as independently predicted by age and night
      SBP fall. Journal of Human Hypertension (2001) 15, 41-48

PMID- 11224002
TI  - Haplotypes of the human renin gene associated with essential hypertension and
      stroke.
AB  - The human renin gene (REN) is a good candidate in studies aimed at unravelling
      the genetic basis of essential hypertension and stroke. We previously established
      that both a BglI and an MboI dimorphisms (located respectively in the first and
      ninth introns of the REN gene) were associated with essential hypertension in a
      population of hyperlipidaemic US subjects. In this association (retrospective
      case-control) study, we investigated the haplotype distribution of alleles
      defined by the combination of REN BglI and MboI dimorphic sites in 329
      hyperlipidaemic US Caucasian subjects referred to UCSF Medical Center (140
      hypertensives, 141 normotensives, and 48 hypertensive patients who had suffered a
      stroke). A statistically significant association was found between alleles
      determined by both (BglI(-)/MboI(+)) and (BglI(+)/MboI(+)) haplotypes and
      clinical diagnosis of EHT (combined odds ratios, OR = 3.35, corrected P < 10(
      7)). Haplotypes (-,+) and (+,+) were also found to be associated with clinical
      diagnosis of stroke (OR = 4.31, P < 10(-7)). These associations do not occur
      through the effects of classical risk factors related to lipid, lipoprotein and
      apolipoprotein levels. We conclude that variations of the REN (or of a nearby)
      gene that may be in linkage disequilibrium with REN (BglI(-)/MboI(+)) and
      (BglI(+)/MboI(+)) alleles could play a role in contributing to increased
      individual's genetic susceptibility to EHT and to stroke. Journal of Human
      Hypertension(2001) 15, 49-55

PMID- 11224003
TI  - Improvement of patients' knowledge by a single educational meeting on
      hypertension.
AB  - OBJECTIVES: A poor therapeutic compliance is a major cause of insufficient
      control of hypertension. As education of patients is fundamental in order to
      improve their compliance, we organised two pilot educational meetings aimed at
      (1) assessing the support of patients to this kind of meetings, and (2) verifying
      the impact on patient's education. METHODS: We invited 225 consecutive patients
      referred to our Hypertension Clinic (some of them regularly followed up and some
      referred for the first time) to participate to an educational meeting on
      hypertension. Patients were divided in two groups, for organising reasons each
      attending a single meeting. Each meeting included four sessions: (1) the first
      session included a multiple choice questionnaire (nine questions, with answers
      collected by an interactive electronic system) in order to evaluate the degree of
      patient's information about hypertension (definition, prevalence, aetiology,
      complications and treatment), (2) a traditional teaching session, (3) an
      interactive phase aimed to assess the improvement of knowledge in which the same
      questions as in the first session have been asked again, and (4) a general
      discussion session. RESULTS: A total of 144 patients (mean age 54 +/- 12 years;
      76 M, 68 F) of the 225 invited attended the meeting. The answers to our questions
      in the initial session were correct in a percentage ranging from 60% to 80%.
      During the third phase immediately after the teaching session, the percentage of
      correct answers increased significantly (range: 75--98%, P < 0.05 at least in all
      questions). CONCLUSIONS: This study shows: (1) a satisfactory adherence of
      patients to this educational initiative; (2) a positive impact of a single
      educational meeting on patient's knowledge about issues related to hypertension.
      The potential role of improving patient's education on clinical outcomes such as
      blood pressure levels and the rate of blood pressure control requires future
      controlled studies. Journal of Human Hypertension (2001) 15, 57-61

PMID- 11224004
TI  - The spatial QRS-T angle as a marker of ventricular repolarisation in
      hypertension.
AB  - Ventricular repolarisation abnormalities are important in arrhythmia provocation.
      The dispersion of repolarisation duration is not the only aspect of
      repolarisation heterogeneity. Spatial vectorcardiographic descriptors constitute
      a novel approach to quantify ventricular repolarisation. To test the ability of
      vectorcardiographic descriptors to discriminate between hypertensives with high
      or low blood pressure (BP), 110 treated hypertensives (mean age 63.6 +/- 12.1
      years) were classified in the high (systolic BP > or = 160 mm Hg or diastolic BP
      > or = 95 mm Hg) (n = 67), or the low (systolic BP < 160 mm Hg and diastolic BP
      <95 mm Hg) (n = 43) BP group. The maximum QT, JT, and T peak-T end intervals and
      the QT, JT, and T peak--T end dispersion were calculated from a digitally
      recorded 12-lead electrocardiogram (ECG). X, Y, and Z leads were reconstructed
      from the 12-lead ECG. The amplitude of the maximum spatial T vector (spatial T
      amplitude), the angle between the maximum spatial QRS and T vectors (spatial QRS
      T angle) and the frontal plane QRS-T angle were calculated. The spatial QRS-T
      angle was higher in patients with high compared to those with low BP (P = 0.025).
      All conventional ECG markers of the dispersion of ventricular repolarisation
      duration failed to demonstrate significant differences between hypertensives with
      high or low BP. In conclusion, the spatial QRS-T angle was significantly
      increased in those treated hypertensive patients who showed repeatedly high BP
      values. Hence, we may suggest that the angle between the directions of
      ventricular depolarisation and repolarisation is a sensitive marker of the
      repolarisation alterations in systemic hypertension. Journal of Human
      Hypertension (2001) 15, 63-70

PMID- 11224005
TI  - Should we do an oral glucose tolerance test in hypertensive men with normal
      fasting blood-glucose?
AB  - The objective of this study was to examine, using the new WHO criteria for
      diabetes mellitus, whether insulin and glucose before and after an oral glucose
      tolerance test would predict cardiovascular mortality in hypertensive men with
      normal fasting blood glucose. A standard oral glucose challenge was performed
      after an overnight fast in 113 hypertensive men with either hypercholesterolaemia
      or smoking. These patients were recruited from an on-going risk factor
      intervention study. The mean observation time was 6.3 years. During follow-up
      there were 10 cardiovascular deaths. The Cox regression analyses showed an
      independent and significant association (P < 0.05) between blood glucose 120 min
      after the glucose ingestion and cardiovascular death during follow-up. Fasting
      glucose, fasting insulin and insulin 120 min after glucose ingestion was not
      related to cardiovascular death during follow-up. In conclusion, this is the
      first study using the current definition of diabetes mellitus showing that
      hyperglycaemia following an oral glucose load is an independent risk factor for
      cardiovascular death in hypertensive men with a normal fasting glucose. In this
      type of hypertensive patient with normal fasting glucose, an oral glucose
      tolerance test may help to identify subjects at high cardiovascular risk. Journal
      of Human Hypertension (2001) 15, 71-74

PMID- 11224006
TI  - Two cases of adrenocortical carcinoma presenting as Conn's syndrome.

PMID- 11224007
TI  - Post traumatic stress disorder and spinal cord injuries.
AB  - Post Traumatic Stress Disorder (PTSD) was first recognised by psychiatric
      international classification systems in 1980 and a wealth of research and
      treatment literature has developed since. This paper provides a review of PTSD
      and Spinal Cord Injuries. A brief history of the disorder is provided before
      descriptions of the defining characteristics, assessment and differential
      diagnoses. The paper provides an overview of the incidence and prevalence of PTSD
      and risk factors within the general population, before considering both veteran
      and non-veteran research within spinal cord injuries. Pharmacological and
      psychological approaches to the treatment of PTSD are also discussed. The review
      closes with recommendations for future research into the prevalence and treatment
      of PTSD in spinal cord injuries.

PMID- 11224008
TI  - Neurological deterioration years after closure of myelomeningocoele - 'the second
      lesion'.

PMID- 11224009
TI  - Factors associated with sleep apnea in men with spinal cord injury: a population
      based case-control study.
AB  - OBJECTIVE: To characterize a population of spinal cord injury (SCI) patients with
      sleep apnea, and to determine associated factors and comorbidities. STUDY DESIGN:
      Population-based retrospective case-control study. SUBJECTS: 584 male patients
      served by a Veterans Affairs SCI service. MEASURES: Medical records were reviewed
      for sleep apnea diagnosis, demographic information, neurologic characteristics,
      and treatments received. Sleep study reports were not available to determine the
      nature of abnormal respiratory events (ie central, obstructive, hypoventilation).
      For each case with tetraplegia, a control tetraplegic subject without sleep apnea
      diagnosis was selected. RESULTS: We identified 53 subjects with diagnosed sleep
      apnea: 42 tetraplegic, 11 paraplegic. This represented 14.9% of all tetraplegic
      and 3.7% of all paraplegic patients in the population (P<0.0001 for comparison of
      tetraplegic and paraplegic proportions). In tetraplegic subjects, sleep apnea was
      associated with obesity and more rostral motor level, but not with ASIA
      Impairment Scale. Medical comorbidities associated with sleep apnea in non-SCI
      patients, such as hypertension, were more common in case subjects. Less than half
      of case subjects were receiving some form of treatment. For motor-complete
      tetraplegics, long-term positive airway pressure treatment was less common with
      motor level C5 and above compared to C6 and below. CONCLUSION: In this
      population, sleep apnea has been frequently diagnosed, particularly in
      tetraplegic subjects. The true prevalence is likely to be considerably higher,
      since this study considered only previously diagnosed cases. Sleep apnea was
      associated with obesity and higher neurologic level, but not ASIA Impairment
      Scale. Medical comorbidities were more frequent in this group, and treatment
      acceptance was poor with higher level motor-complete injuries. Since the type of
      sleep apnea (central or obstructive) was not distinguished, we cannot comment on
      the prevalence and associations based on specific types of sleep apnea.

PMID- 11224010
TI  - Vesicoureteral reflux in the early stage of spinal cord injury: a retrospective
      study.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVES: To investigate the risk factors
      of vesicoureteral reflux in the early stage of spinal cord injury. SETTING:
      Japan. METHODS: Urological evaluation, including cystography and urodynamic study
      was performed in patients in the early stage of spinal cord injury. The patients
      were divided into two groups. Group 1 included 13 patients with vesicoureteral
      reflux. Group 2 included 97 patients without vesicoureteral reflux. We compared
      Group 1 and Group 2 regarding bladder deformation, the level of spinal cord
      injury, bladder behaviour, bladder compliance, high urethral closure pressure and
      method of urine evacuation. RESULTS: The patients injured between Th10 and L2
      showed a significantly higher incidence of vesicoureteral reflux than those
      injured in other areas (P<0.01). Furthermore, bladder compliance among patients
      with vesicoureteral reflux tended to be low. Other factors showed no differences
      between patients with and without vesicoureteral reflux. CONCLUSION: Injuries
      between Th10 and L2 involve the sympathetic nervous system. Patients with such
      injuries often exhibited vesicoureteral reflux in the early stage of spinal cord
      injury.

PMID- 11224011
TI  - Cranberry juice consumption may reduce biofilms on uroepithelial cells: pilot
      study in spinal cord injured patients.
AB  - STUDY DESIGN: A pilot study of 15 spinal cord injured patients. OBJECTIVE: To
      determine whether alteration of fluid intake and use of cranberry juice altered
      the bacterial biofilm load in the bladder. SETTING: London, Ontario, Canada.
      METHODS: Urine samples were collected on day 0 (start of study), on day 7
      following each patient taking one glass of water three times daily in addition to
      normal diet, and on day 15 following each patient taking one glass of cranberry
      juice thrice daily. One urine sample was sent for culture and a second processed
      to harvest, examine by light microscopy and Gram stain non-squamous uroepithelial
      cells to generate bacterial adhesion per 50 cells data. RESULTS: The results
      showed that cranberry juice intake significantly reduced the biofilm load
      compared to baseline (P=0.013). This was due to a reduction in adhesion of Gram
      negative (P=0.054) and Gram positive (P=0.022) bacteria to cells. Water intake
      did not significantly reduce the bacterial adhesion or biofilm presence.
      CONCLUSION: The findings provide evidence in support of further, larger clinical
      trials into the use of functional foods, particularly cranberry juice, to reduce
      the risk of UTI in a patient population highly susceptible to morbidity and
      mortality associated with drug resistant uropathogens. SPONSORSHIP: This study
      was funded by Ocean Spray Cranberries, Lakeville, MA, USA.

PMID- 11224013
TI  - Hand function of C6 and C7 tetraplegics 1 - 16 years following injury.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To quantify the hand
      function of C6 and C7 tetraplegics 1 - 16 years after injury. SETTING: Patients
      were assessed in their homes. METHODS: Medical records of patients admitted to
      the Prince Henry Hospital Spinal Injuries Unit between 1984 and 1999 were used to
      identify all patients with C6 or C7 tetraplegia at 3 months post injury. Sixty
      five patients (107 hands) were identified in this way. Forty-seven patients (81
      hands) were located and agreed to partake in the study, and seven (nine hands)
      had died. Thus 81% of patients (83% of hands) still alive at follow-up were
      assessed. MAIN OUTCOME MEASURES: Unilateral hand function was assessed with the
      Grasp and Release Test (GRT) and a 10 item Activities of Daily Living (ADL) Test.
      Prevalance and severity of contractures, lateral grasp (key grip) strength and
      extensibility of the extrinsic finger flexor muscles were also determined.
      RESULTS: All hands except one had been managed without surgical intervention. The
      median number of ADL tasks successfully completed was 9/10 (interquartile range=8
      - 10) and the median number of objects successfully manipulated in the GRT was
      3/6 (IQ range=3 - 5). Lateral grasp was poor (74% and 75% of hands could not use
      a lateral grasp to move the paperweight or depress the fork in the GRT,
      respectively), and the prevalence of contractures was low (53% of hands had full
      passive range of motion). CONCLUSION: In the long term, most C6 and C7
      tetraplegics attain a high level of hand function despite poor lateral grasps.

PMID- 11224012
TI  - Evaluation of spinal cord blood flow during prostaglandin E1-induced hypotension
      with power Doppler ultrasonography.
AB  - STUDY DESIGN: Intraoperative power Doppler ultrasonography was used to evaluate
      the spinal cord blood flow in cervical spondylotic myelopathy patients during
      hypotensive anesthesia. OBJECTIVE: To evaluate the effect of prostaglandin E1
      (PGE1) induced hypotension on spinal cord blood flow (SBF) during spinal surgery.
      SUMMARY AND BACKGROUND DATA: Hypotension is frequently induced to decrease blood
      loss during surgery and to diminish the need for blood transfusion. Prostaglandin
      E1 (PGE1) is reported to maintain cerebral, liver, and renal blood flow during
      surgery. However, there are few reports on spinal cord blood flow. METHODS:
      Eleven patients underwent laminoplasty for cervical spondylotic myelopathy. After
      a French door type laminoplasty was carried out, hypotension was induced with
      PGE1. Before and during hypotension, we evaluated blood flow in the anterior
      spinal cord artery by determining the pulsatility index (PI) and resistance index
      (RI) using power Doppler ultrasonography. RESULTS: Before hypotension, the mean
      blood pressure was 80 mmHg. The blood pressure decreased to 60 mmHg using PGE1
      (P<0.01), although the PI and RI were significantly higher than before
      hypotension (PI, P=0.0076 RI, P=0.02). CONCLUSION: The pulsatility and resistance
      indices during hypotension were significantly higher than before hypotension,
      suggesting that the autoregulation of the anterior spinal cord artery and
      anterior spinal cord blood flow were maintained with hypotension using PGE1.
      Prostaglandin E1 may be a useful drug for hypotensive anesthesia in spinal
      surgery.

PMID- 11224014
TI  - Pain treatment satisfaction in spinal cord injury.
AB  - STUDY DESIGN: A survey on pain satisfaction was mailed to 300 individuals with
      spinal cord injury. Eighty-eight completed surveys were returned, and the results
      were analyzed. OBJECTIVES: The survey queried the respondents on characteristics
      of their pain, treatments received, the impact of pain on multiple, life
      activities and functions and the satisfaction with treatment received to reduce
      pain. SETTING: Subjects for the study were selected from the Spinal Cord Injury
      Registry from the Commonwealth of Virginia in the US. METHODS: Information was
      obtained from a survey sent to the subjects who were chosen randomly with respect
      to age and gender. At least 1 year had elapsed from the time of injury for each
      individual. RESULTS: Respondents were typically dissatisfied with the results of
      the treatments received to manage their pain. CONCLUSION: Pain in individuals
      with spinal cord injury needs to be addressed in a thorough fashion to reduce the
      adverse impact on life activities.

PMID- 11224015
TI  - Nursing care in spinal cord injuries in Turkey.
AB  - The organized management of spinal cord injury is a team activity and the nurse
      is at the central position of that team. Nursing activities and caring should be
      superior in a spinal cord injury rehabilitation department. Nevertheless, nurses
      seldom undertake caring activities and usually perform therapeutic activities in
      developing countries. We recorded the care of 15 spinal cord injured patients
      around the clock for 10 working days. We asked the nurses, patients and their
      family carers to record every activity they performed on the forms. The
      activities were as follows: Oral care, face care, hand care, foot care, nail
      care, genitalia care, perineal care, catheterization, head bath, bed bath, bath,
      positioning, mobilization, exercising, wound dressing, room activities and the
      other nursing activities. The total number of nursing activities, performed was
      3573. Subtotals were as follows: 2545 caring activities, 364 room activities, and
      664 other nursing activities. While nurses performed 550 of the caring
      activities, patients and their family carers performed 988 and 1007 patient care
      activities. The distribution of the nurses' activities was as follows: 40% for
      caring, 11% for room activities, 48% for others. We discuss the importance of
      caring activities and the role of nurses in the rehabilitation team.

PMID- 11224016
TI  - The earliest case of cauda equina syndrome caused by manipulation of the lumbar
      spine under a general anaesthetic.
AB  - Jonathan Hutchinson described a 42-year-old man with a previous history of
      alternating sciatica who had crushing of a pile under ether anaesthesia in 1889.
      When the patient awoke from the anaesthetic he had paralysis of his bladder and
      bowels. Jonathan Hutchinson could not establish a diagnosis. Evidence is
      presented to suggest that this was the first case of a prolapsed disc causing a
      cauda equina lesion as a result of anaesthesia and manipulation.

PMID- 11224017
TI  - Compression of femoral vein by the strap of a urine-collecting device in a spinal
      cord injury patient.
AB  - OBJECTIVE: To report an unusual cause of femoral vein compression in a spinal
      cord injury (SCI) patient. DESIGN: A case report of a SCI patient in whom the
      strap of a urinal produced compression of femoral vein. Setting Regional Spinal
      Injuries Centre, Southport, England. SUBJECT: A 65-year old male, who had
      sustained paraplegia at T-10 level 33 years ago, attended the spinal unit for a
      routine follow-up intravenous urography (IVU). He was wearing a urinal, which was
      held tightly over the penis by means of two straps coursing over the inguinal
      regions. MAIN OUTCOME MEASURES: IVU was performed by injecting 50 ml of Ultravist
      300 via a 23-gauge butterfly needle inserted in a vein over the dorsum of the
      left foot. After completion of the injection, an X-ray of the pelvis was taken to
      evaluate the right hip. This showed contrast in the vena profunda femoris,
      circumflex femoral veins and inter-muscular veins with evidence of compression of
      proximal femoral vein. RESULTS: It was suspected that the strap holding the
      urinal was causing compression of the femoral vein. Therefore, a venogram was
      performed 5 days later, when the patient had discarded the urinal and the straps.
      This showed free flow of contrast through the left femoral and iliac veins.
      CONCLUSION: Compression of femoral vein by a strap holding the urinal was
      discovered serendipitously in this patient during a routine follow-up. Physicians
      and health professionals should bear in mind this rare complication when
      examining spinal cord injury patients who use this type of urine collecting
      device, and discuss with them alternative methods for urinary drainage.

PMID- 11224018
TI  - Spinal solitary fibrous tumor: seventh reported case and review of the
      literature.
AB  - We present the clinical, radiological, and pathological features of a solitary
      fibrous tumor in the spinal cord. This case is the seventh spinal solitary
      fibrous tumor in the literature. The tumor caused clinical symptoms in a 70-year
      old female, which indicated compression of the spinal cord. Magnetic resonance
      imaging showed an intradural extramedullary mass at T3 vertebral level.
      Surgically, the tumor was firm, in an intradural extramedullary location and
      attached to the dura. Histologically, the tumor was composed of spindle cells in
      a collagen-rich matrix but exhibited regional variations. CD34 and vimentin were
      diffusely positive during immunohistochemical stain testing. The tumor displayed
      no positive staining for epithelial membrane antigen, cytokeratin, S-100 protein,
      smooth muscle actin or desmin. The Ki-67 labeling index was low. Solitary fibrous
      tumors have been found in a variety of locations suggesting that a solitary
      fibrous tumor has a mesenchymal origin. This rare tumor should be considered in
      the differential diagnosis of spinal tumors.

PMID- 11224019
TI  - The adolescent with simple or corrected congenital heart disease.
AB  - An ever-increasing number of congenital heart disease patients are surviving into
      and beyond adolescence. Despite the encouraging cardiac results, with the vast
      majority asymptomatic and requiring no medication and having few, if any,
      limitations, there are many challenges for this patient population. They are
      likely to find obstacles to attaining education, social development, health and
      life insurance, and employment. Most of these obstacles are attributable to the
      stresses upon children with congenital heart disease and their families, and the
      prejudices of a society that knows little about congenital heart disease.
      Practitioners caring for these young people must be familiar with these issues
      and knowledgeable about the facts of individual cases, so that they may
      anticipate needs and offer support to their patients in their progress toward
      adulthood.

PMID- 11224020
TI  - Palliated congenital heart disease.
AB  - The group of patients with palliated complex forms of congenital heart disease
      presents a challenging and difficult management problem during the adolescent
      years. In patients not considered to be candidates for more fully palliated
      procedures that separate the circulations, a bidirectional caval pulmonary shunt,
      often associated with a systemic to pulmonary shunt, may provide significant
      palliation for several more decades. However, there remain a significant number
      of patients who, after some years, may develop increasing problems associated
      with myocardial failure and the development of serious atrial arrhythmias.
      Interventional cardiac catheterization combined with newer surgical techniques
      may return many of these patients to more satisfactory hemodynamic states.
      However, some patients during their adolescent years may eventually require
      cardiac transplantation for the long-term management of their complex congenital
      cardiac defects.

PMID- 11224021
TI  - Cardiomyopathies in adolescents: dilated, hypertrophic, and restrictive.
AB  - Three major types of cardiomyopathies affect adolescents: dilated, hypertrophic,
      and restrictive. At the present time the etiologies of the majority of these
      cardiomyopathies in children remain elusive. Treatment of these diseases is
      generally directed toward improving symptoms, survival, myocardial performance,
      and hemodynamics. Most treatment strategies are extrapolated from studies in
      adults with these types of cardiomyopathies, although prospective, randomized
      therapeutic trials are currently underway in children. All three types of
      cardiomyopathy can be associated with a wide range of symptoms (from none to
      severe) and also are associated with sudden death. For those in whom medical
      management fails, heart transplantation is a therapeutic option with an excellent
      intermediate-term success rate.

PMID- 11224022
TI  - Myocarditis and pericarditis in adolescents.
AB  - Two of the most common inflammatory disorders affecting the heart, myocarditis
      and pericarditis, are significant causes of morbidity and mortality in
      adolescents. In this review, the clinical presentation, underlying etiologies,
      and treatment options for these disorders are discussed. As viral causes of both
      disorders are commonplace, issues regarding the identification of the causative
      virus and potential future approaches to the care of these individuals are also
      discussed.

PMID- 11224023
TI  - Cardiac involvement in inflammatory disease: systemic lupus erythematosus,
      rheumatic fever, and Kawasaki disease.
AB  - This review focuses on treatment and preventive issues relevant to cardiac
      problems associated with systemic lupus erythematosus, acute rheumatic fever, and
      Kawasaki disease in adolescence. Cardiac abnormalities occur as a result of the
      immune dysfunction and as side effects of therapy. With increased survival, more
      cardiac complications are being detected. Screening for cardiac risk factors,
      such as cigarette smoking, hypertension, obesity, and hypercholesterolemia,
      should begin in adolescence.

PMID- 11224024
TI  - Diagnosis and treatment of pulmonary hypertension in the adolescent.
AB  - This article discusses diagnostic and therapeutic options of adolescents with
      primary and secondary pulmonary hypertension. Pulmonary hypertension is an
      important determinant of morbidity and mortality in many diseases, including
      congenital heart disease and respiratory disease. Previously, the diagnosis of
      pulmonary hypertension in children carried a poor prognosis. However, advances in
      the diagnosis and treatment of pulmonary hypertension over the last decade have
      markedly improved survival of many patients. A targeted approach includes
      treatment of the underlying disease, and therefore requires an extensive
      evaluation. Many of the treatment modalities are based on advanced understanding
      of basic pulmonary vascular biology.

PMID- 11224025
TI  - Chest pain in the adolescent.
AB  - Chest pain invokes serious concern in adolescents, their families, and their
      primary care physicians. These concerns are fueled by media reports of sudden
      death in high-profile athletes and the high incidence of ischemic heart disease
      in our society. However, chest pain in this age group is usually benign and a
      careful clinical evaluation including a detailed history and physical examination
      may guide the clinician in reaching a diagnosis, obtaining the appropriate
      diagnostic studies, and making the proper referrals to specialists.

PMID- 11224026
TI  - Syncope and sudden death in the adolescent.
AB  - Syncope is the sudden loss of consciousness and postural tone resulting from an
      abrupt, transient cerebral malfunction, followed by spontaneous recovery. It is
      common among adolescents and is usually due to a benign neurocardiogenic
      (vasovagal) etiology. Rarely, syncope is premonitory of sudden death. The
      physician must be knowledgeable about the characteristics of neurocardiogenic
      syncope and what distinguishes it from life-threatening causes. Evaluation of
      syncope should be based on a complete personal and family history, a thorough
      physical examination, and an electrocardiogram. Risk factors include syncope that
      is recurrent, exercise-induced, or not neurocardiogenic in nature; accompanying
      anginal chest pain, palpitations, and/or dyspnea; cardiac disease; seizure
      activity; athletic competition; and positive family history for conditions
      associated with sudden death (e.g., hypertrophic cardiomyopathy, long QT
      syndrome). Adolescents with these risk factors should be referred to a pediatric
      cardiologist for specialized testing and management.

PMID- 11224027
TI  - Toxic exposures.
AB  - Adolescence is a time of immense physical and social change. Risk-taking behavior
      is commonplace and often includes experimentation with various illicit drugs.
      Toxic ingestions remain a significant medical problem in this population. The
      major objective of this review is to provide an overview of the more common toxic
      exposures in adolescents. A framework is presented for understanding some of the
      factors that result in substance abuse in adolescents. Signs, symptoms and
      clinical manifestations of commonly abused drugs are presented along with general
      approaches to management of acute overdose. As the population of adolescents with
      underlying heart disease continues to grow, it is important for primary care
      providers to individualize treatment of adolescents with congenital or acquired
      heart disease. The impact of pre-existing cardiac disease is briefly reviewed.

PMID- 11224028
TI  - Cardiovascular risk factors in adolescents: relevance, detection, and
      intervention.
AB  - Recent epidemiologic studies have documented worrisome trends towards increasing
      obesity and increased cigarette smoking in adolescents. Since cardiovascular risk
      factors have been shown to persist into adulthood, this may translate into an
      epidemic of cardiovascular disease in the future. Health care providers should
      assume some responsibility for the prevention, detection, and intervention
      relevant to cardiovascular risk factors in adolescents, which include
      hyperlipidemia, hypertension, obesity, and tobacco use. Promotion of a healthy
      lifestyle, including a low-fat prudent diet, regular physical activity, and
      avoidance of risky behaviors should be incorporated into health maintenance
      encounters. Interventions directed at the adolescent must take into account their
      social milieu, particularly the family, school, and community. Adolescents should
      be empowered through education and skill development to assume increasing
      responsibility for their own health behaviors.

PMID- 11224029
TI  - Gynecologic and obstetric issues in the adolescent with heart disease.
AB  - It is necessary to adopt a proactive, prevention-based strategy for addressing
      gynecologic and obstetric issues in the adolescent with heart disease. Pregnancy
      carries known cardiovascular alterations, manifestations and risks. The nature of
      the underlying cardiac disease needs to be considered in preconception counseling
      and in the prevention of pregnancy. Specific risks of oral contraceptive methods
      must be considered as well. Estrogen-based oral contraceptives may confer risks
      of thromboembolic phenomenon, whereas progesterone-based agents may be associated
      with increased risk of bleeding. Medical termination of pregnancy may pose risks
      to the young woman with cyanotic heart disease or pulmonary hypertension. Full
      prepregnancy evaluation helps to ensure a good outcome for both mother and baby.
      There are risks of continuing specific cardiovascular medications during
      pregnancy; however, certain medications are continued to safeguard maternal
      health. This is particularly problematic in the patient who must remain on
      anticoagulation.

PMID- 11224030
TI  - Latent learning in a radial arm maze following neonatal dopamine depletion.
AB  - Animals neonatally depleted of dopamine show decreases in exploratory behaviour.
      As latent learning may depend on exploratory behaviour the present study was
      undertaken to examine the effects of neonatal dopamine depletion on latent
      learning. In two experiments dopamine was depleted neonatally, using 6
      hydroxydopamine injected intracisternally on day 1 after birth. In both
      experiments, exploratory behaviour, measured as rearing and head-dip responses in
      a modified openfield/holeboard, was reduced in the dopamine depleted rats whereas
      ambulatory behaviour was elevated. In a modified radial arm maze also, rearing
      responses were decreased while ambulation was increased for the 6-hydroxydopamine
      treated rats. Latent learning was tested in each experiment following preexposure
      to the maze for either a single trial or four trials. 6-Hydroxydopamine treated
      rats demonstrated a comparable latent learning effect to vehicle treated rats
      after four maze exposures but showed a greatly attenuated latent learning effect
      following only a single exposure. It is suggested that the effects of neonatal
      dopamine upon maze and latent learning are secondary to the effects on
      hyperactivity, reduced exploration and/or increased neophobia shown by these
      rats.

PMID- 11224031
TI  - Acute versus chronic clonidine treatment effects on conflict behavior in the rat.
AB  - The present study examined the effects of acute and chronic treatment with the
      alpha-2-adrenoceptor agonist clonidine on behavior in the Conditioned Suppression
      of Drinking (CSD) conflict paradigm, an animal model for the study of anti
      anxiety treatments. In daily 10-min sessions, water-deprived rats were trained to
      drink from a tube which was occasionally electrified (0.25mA). Electrification
      was signalled by a tone. Within 3-4 weeks of 4 day/week CSD sessions, control
      (i.e. non-drug) CSD behavior had stabilized (approximately 40 shock/session and
      11ml water/session). Acute treatment with clonidine across a range of doses (1.25
      40ug/kg; 10-min pretreatment) did not exert an anti-conflict effect, with doses
      greater than 5ug/kg significantly depressing unpunished responding (i.e. water
      intake). Similarly, administration of a single dose of clonidine (40ug/kg) across
      a range of pretreatment times (10 to 120min) failed to increase punished
      responding. In contrast, chronic post-test treatment with clonidine (40ug/kg,
      twice daily for 18 weeks) resulted in a dramatic and time-dependent increase in
      punished responding, with a latency to onset of approximately 3-4 weeks. The
      response to an acute challenge with chlordiazepoxide (10mg/kg) or the
      benzodiazepine antagonist Ro 15-1788 (4.0mg/kg) did not differ in chronic
      clonidine-versus saline-treated subjects, indicating that benzodiazepine receptor
      sensitivity had not been affected by this chronic clonidine treatment. An acute
      challenge with a low dose of clonidine (10ug/kg) decreased punished and
      unpunished responding in chronic clonidine- or saline-treated subjects. Finally,
      an acute challenge with the alpha-2-antagonist yohimbine (1.25mg/kg) failed to
      block the increase in punished responding associated with chronic clonidine
      treatment, indicating that the anti-conflict effect of this chronic post-test
      clonidine treatment was not the result of alpha-2-adrenoceptor activation at the
      time of CSD testing (i.e. not due to drug accumulation). Discontinuation of
      chronic clonidine treatment resulted in a decline to near saline-treated levels
      of punished responding over the course of 3 weeks of conflict testing. The
      relationship of these findings to the anti-anxiety effects of clonidine in humans
      are discussed.

PMID- 11224032
TI  - Spatial pattern analysis reveals similarities between amphetamine conditioned and
      unconditioned locomotion.
AB  - The repeated injection of drugs which increase locomotion, paired with a
      distinctive testing environment, has been shown to result in conditioned
      hyperactivity upon subsequent exposure to the environment alone. Unknown,
      however, are the form and characteristics of the behavioral response that makes
      up the conditioned hyperactivity. Conditioned and unconditioned locomotor
      responses in rats were compared with a computerized Behavioral Pattern Monitor
      (BPM), a system which provides detailed information regarding the amount and
      qualitative patterning of locomotor activity and investigatory responses. After
      an initial 2h exposure to the BPM chambers (baseline day), rats were randomly
      assigned into one of two groups and injected each day with saline or 0.75mg/kg
      amphetamine (AMPH) prior to placement in the BPM chambers for a 2h experimental
      session. Rats were then returned to their home cages and injected with the
      alternate solution. This procedure was repeated for 5 days, and on the sixth day
      all rats were injected with saline prior to placement in the BPM. Rats that had
      received AMPH/BPM pairings exhibited significant increases in horizontal
      locomotion, rearing and investigatory holepokes on the test day compared to rats
      that received saline/BPM pairings. The AMPH group also exhibited an increased
      sensitivity to a physical movement of the test chambers. Analyses of the daily
      locomotor paths for each rat using transition matrices revealed that the
      conditioned activity measured on the test day resembled the last AMPH day more
      than either the first AMPH day or the predrug baseline day. These descriptive
      measures of each animal's spatial patterns of locomotion suggest that the
      particular pattern induced by AMPH in each animal stabilized over time and became
      conditioned to environmental cues. In this case, the increased motor activity
      observed on the test day was qualitatively similar to the unconditioned response
      produced by AMPH.

PMID- 11224033
TI  - The generation of adjunctive behavior under conditions of drug self
      administration.
AB  - The generation of adjunctive behavior was studied in rhesus monkeys responding
      under fixed-interval (FI) schedules of food pellet delivery or intravenous (iv)
      infusions of cocaine or midazolam. The FI schedule value ranged from 1.5 to
      120min. Each response on a second, concurrently available lever resulted in an
      infusion of saline. The number of saline infusions received was a bitonic
      function (inverted U) of the interval of reinforcer (food or drug) delivery. This
      bitonic function is characteristic of adjunctive behavior and strongly suggests
      that the responding that results in the infusion of saline was an adjunctive
      behavior. Furthermore, these results establish that intermittent schedules of
      drug delivery can generate adjunctive behavior. Increases in the dose of drug
      self-administered shifted the bitonic function of saline infusions to the right.
      This shift in the function of adjunctive behavior is consistent with the
      hypothesis that the generation of adjunctive behavior is dependent upon both the
      magnitude and the intermittent delivery of the reinforcer.

PMID- 11224034
TI  - Performance of a passive avoidance response is disrupted by compounds acting at
      5HT(1A) receptors.
AB  - In a previous study it was found that the anxiolytic drug buspirone and the
      related compounds gepirone and ipsapirone disrupted the performance of a passive
      avoidance response by rats. A similar effect was not produced by several other
      drugs including chlordiazepoxide, imipramine and haloperidol. In the present
      study the same procedure was used to investigate whether other compounds known to
      interact with serotonergic mechanisms would produce a similar effect. The 5HT(1A)
      agonists 8-OH-DPAT and MDL-72832 produced similar disruptions in the performance
      of a step-down passive avoidance response (i.e. decreased latencies), with 8-OH
      DPAT giving rise to a bell-shaped dose-response curve. Neither ritanserin, a
      5HT(2) antagonist, nor 1-PP, a metabolite of buspirone known to have alpha(2)
      adrenoceptor antagonist properties, was active. Odansetron (GR38032F), a 5HT(3)
      antagonist, was active, although the magnitude of the effect was smaller than
      that seen with the 5HT(1A) agonists and was not clearly dose-related. In drug
      interaction experiments the effect of 8-OH-DPAT was completely eliminated after
      treatment with NAN-190 although NAN-190 itself increased step-down latencies. The
      effect of 8-OH-DPAT was also partially blocked by prazosin. Thus the performance
      of a step-down passive avoidance response is disrupted by a range of compounds
      known to be 5HT(1A) agonists but by few other drugs.

PMID- 11224035
TI  - Peripherally administered alpha-methyl-5-hydroxy-tryptamine and 5
      carboxamidotryptamine reduce food intake via different mechanisms in rats.
AB  - Peripherally administering the serotonin (5-HT) analogs, alpha-methyl-5
      hydroxytryptamine (alpha-Me-5-HT) and 5-carboxamidotryptamine (5-CT), reduced
      milk consumption by food-deprived rats. 5-CT decreased milk intake 100-fold more
      potently than alpha-Me-5-HT (ID(50)'s =.06 and 5.6umol/kg, respectively). 5-CT
      also elicited drinking but alpha-Me-5-HT did not. The nonselective 5-HT
      antagonist, methysergide, blocked the anorectic actions of each agonist. By
      contrast, the 5-HT(2) antagonist, ketanserin, and the peripheral 5-HT(2)
      antagonist, xylamidine, only prevented anorexia due to alpha-Me-5-HT. These
      results suggest that stimulating either peripheral 5-HT(2) or peripheral 5-HT(1)
      like receptors inhibits feeding in rats. 5-HT(1)-like sites may also mediate 5-HT
      induced drinking.

PMID- 11224036
TI  - Comparison of effects of buspirone and gepirone with benzodiazepines and
      antagonists of dopamine and serotonin receptors on punished behavior of rats.
AB  - Lever-press responding of male Sprague-Dawley rats was maintained under a
      conflict procedure in which every tenth response produced both food and electric
      shock (punished responding); every thirtieth response produced only food in the
      presence of a separate stimulus. The benzodiazepines, diazepam and
      chlordiazepoxide, increased responding 4- to 6-fold. Buspirone and its structural
      analog, gepirone, only moderately and inconsistently increased responding (1.5-
      and 2-fold, respectively). The dopamine-2 (D-2) receptor antagonist, sulpiride,
      but not haloperidol had effects similar to buspirone. The D-1 antagonist SCH
      23390 was not active. The non-selective serotonin (5HT) antagonists,
      cyproheptadine and methysergide, consistently increased responding 2-fold, but
      the 5HT-2 antagonists, ketanserin, pirenperone, ritanserin, R-56 413, and LY
      53857 and the 5HT-1A agonist, 8-OH-DPAT, were inactive. In pigeons, serotonergic
      compounds have been shown to increase punished responding. The present results
      suggest that exploitation of this species difference may be helpful in evaluating
      new chemicals for novel anxiolytic activity and for investigation of their
      mechanisms of action.

PMID- 11224037
TI  - Anticonflict-like effect of a prefrontal dopaminergic lesion in rats: permissive
      role of noradrenergic neurons.
AB  - The effects of a perfrontal dopamine (DA) lesion were compared to those induced
      by a combined DA and noradrenaline (NA) lesion, to investigate the permissive
      role of prefrontal NA terminals in the anxiolytic-like effect of a prefrontal DA
      lesion. Lesions consisted of bilateral microinjections of 6-hydroxydopamine into
      the medial prefrontal cortex in rats either given desipramine (25mg/kg) before
      surgery (DA lesion) or not pretreated with desipramine (combined DA and NA
      lesions). Three weeks post-surgery, water-restricted rats, given saline or
      diazepam (2mg/kg), were subjected to a single session in the punished drinking
      test. Prefrontal DA lesions significantly increased punished drinking in saline
      treated rats. This effect was not observed in rats with the dual prefrontal
      lesions. The ability of diazepam to increase punished drinking was not modified
      by either lesion. These data suggest that the integrity of NA afferents to the
      prefrontal cortex is necessary for the anxiolytic-like effect induced by the
      prefrontal DA lesion. The results also indicate that the effect of diazepam is
      not mediated by the prefrontal catecholamine afferents.

PMID- 11224038
TI  - Discriminative stimulus effects of H(1)-anti-histamines in cocaine-trained
      pigeons.
AB  - Pigeons (n = 4) were trained to discriminate cocaine (3.0mg/kg, i.m.) from saline
      in a two-key, food-reinforced drug discrimination paradigm. After acquisition of
      the discrimination, the H(1)-antihistamines, chlorpheniramine, tripelennamine,
      diphenhydramine, promethazine and hydroxyzine, were administered before test
      sessions to determine if these antihistamines shared discriminative stimulus (DS)
      effects with cocaine. Chlorpheniramine (0.3-5.6mg/kg) and tripelennamine (0.1
      1.7mg/kg) substituted, (i.e. > 80% cocaine-key responding) in all four birds.
      Diphenhydramine (0.1-10mg/kg) and promethazine (0.1-56mg/kg) substituted for
      cocaine in three and two birds, respectively, while hydroxyzine (1.0-100mg/kg)
      did not substitute for the training drug in any bird. These results, in
      conjunction with results from a previous study in which several antihistamines
      shared DS effects with d-amphetamine, suggest that the DS effects of some H(1)
      antihistamines may be similar to those of psychomotor stimulants.

PMID- 11224041
TI  - Editorial Announcements Behavioural Pharmacology is now listed in Current
      Contents.

PMID- 11224042
TI  - Discriminative stimulus effects of the novel anxiolytic buspirone.
AB  - Separate groups of Long-Evans rats were trained to discriminate either 0.56 or
      1.0mg/kg buspirone i.p. in a two-lever, drug vs no-drug discrimination procedure.
      Training took twice as long for the lower versus the higher training-dose group.
      Generalization tests were conducted with buspirone (0.1-1.8mg/kg, i.p., 0.32
      10mg/kg, p.o.), pentylenetetrazole (1-18mg/kg, i.p.), meprobamate (3.2-180mg/kg,
      p.o.), haloperidol (0.01-0.32mg/kg, i.p.), and 8-OH-DPAT (0.01-0.32mg/kg, i.p.).
      Buspirone p.o. was 0.5-1.0 log(10) units less potent than buspirone i.p. in
      producing dose-dependent generalization (i.e. > 80% buspirone-lever responding).
      Dose-effect functions for the 1.0 training-dose group were to the right of those
      for the 0.56 group. Partial generalization to meprobamate occurred in both
      groups, representing the first report of overlap of the buspirone discriminative
      stimulus with that of another anxiolytic. Complete generalization to 8-OH-DPAT
      occurred, consistent with buspirone's prominent 5HT(1A)-receptor activity and
      replicating findings in the pigeon. Partial generalization to haloperidol was
      concluded: every rat generalized to haloperidol, but the gradients did not
      increase monotonically and drug-lever responding at a given dose was inconsistent
      within and across rats. The haloperidol results suggest a stronger influence of
      the dopaminergic component in the buspirone discriminative stimulus in rats than
      was found with pigeons. Although a previous study found generalization to
      buspirone from pentylenetetrazole in baboons, there was no generalization to
      pentylenetetrazole from buspirone in the present study.

PMID- 11224043
TI  - Effects of spirometric administration of tobacco smoke containing varying amounts
      of nicotine on physiological measures and subject ratings.
AB  - A previously developed spirometric methodology of tobacco smoke administration
      was evaluated by determining the effects of varying nicotine delivery on various
      physiological and subjective measures. Eight male tobacco smoking subjects were
      administered 60cc volumes of tobacco smoke drawn from University of Kentucky
      research cigarettes, or air. Subjects were exposed to four bouts of smoke
      administration conducted over an 8h day. Each smoking bout was separated by 2h
      and involved 20 smoke administrations at the rate of one every 30sec. Each smoke
      administration consisted of 60cc of air or 60cc drawn from 0.3, 1.2 or 2.7mg
      nicotine yield cigarettes, followed by 1 liter of air which forced the smoke or
      air deep into the lungs. Carbon monoxide (CO), blood pressure, and heart rate
      were measured before and after each smoking bout, and subject ratings of smoke
      effects were completed after each smoking bout. In a separate study, blood
      samples were collected on two occasions before and after administration of the
      two highest nicotine yield cigarettes to determine changes in nicotine plasma
      levels. Data indicated that the spirometric method produced: (1) similar CO
      boosts across nicotine yields, and (2) changes in heart rate, blood pressure,
      subject ratings and plasma nicotine levels which were directly related to the
      nicotine yield of cigarettes.

PMID- 11224044
TI  - Effects of spirometric administration of tobacco smoke containing varying amounts
      of nicotine on human punished and non-punished operant responding.
AB  - Lever pulling of male tobacco smokers was maintained by a variable interval 20sec
      schedule (VI 20) of point presentation. In experiment 1 the rate of lever pulling
      was suppressed by a punishment contingency which stipulated that lever pulls
      would produce point subtractions on a variable ratio 30 schedule (VR 30). In
      experiment 2 the punishment contingency was omitted. Each subject participated in
      eight sessions each day (Mon. through Fri.). Each block of two 20-min sessions
      was separated by a period during which tobacco smoke containing varying amounts
      of nicotine was administered by the spirometry method, which ensured a constant
      puff volume and deep inhalation. The tobacco smoke conditions were: (1) 0.3mg
      nicotine yield cigarettes (baseline condition), (2) 1.2mg nicotine yield
      cigarettes, (3) 2.7mg nicotine yield cigarettes and (4) a condition in which room
      temperature air was administered. Subjects remained at baseline conditions until
      responding stabilized and were then exposed to higher nicotine yield smoke or air
      for an entire day. Subjects were then returned to baseline conditions before
      administration of higher nicotine yield smoke or air. In experiment 1 (punishment
      contingency) lever pulling decreased as a function of increasing nicotine content
      in tobacco smoke. This effect upon responding was similar to the effects of CNS
      stimulants on punished responding in non-human subjects. In experiment 2 (no
      punishment contingency), no consistent effect of tobacco smoke or non-punished
      responding was observed.

PMID- 11224045
TI  - Dihydroergotoxine treatment improves active avoidance performance and increases
      dopamine-stimulated adenylate cyclase activity, in young and aged rats.
AB  - Dihydroergotoxine (DHET) improved the acquisition of a conditioned avoidance
      response in both young and old rats, although old animals, reached a lower
      percentage of conditioned responses than did young rats. DHET dose-dependently
      reduced locomotor activity in aged animals, while, in young rats, increasing
      doses caused a triphasic effect, inhibitory at low doses, stimulatory at
      intermediate doses and again inhibitory at high doses. In young rats, the
      stimulation of spontaneous movements by DHET was abolished by L-sulpiride; L
      sulpiride had no effect in old animals. DHET treatment also potentiated both
      norepinephrine- and, to a greater extent, dopamine-stimulated frontal cortex
      adenylate cyclase activity, an effect more pronounced in young than in old rats.
      These data show that DHET effects both locomotor activity and active avoidance
      performance in young and aged rats, and modulates dopamine-sensitive adenylate
      cyclase activity.

PMID- 11224046
TI  - Effects of tianeptine on spontaneous alternation, simple and concurrent spatial
      discrimination learning and on alcohol-induced alternation deficits in mice.
AB  - The effects of systemic administration of tianeptine, a new psychotropic agent
      with antidepressant properties, were investigated on spontaneous alternation
      behavior, and on simple and concurrent spatial discrimination, in normal mice of
      the BALB/c strain. Tianeptine increased rates of spontaneous T-maze alternation,
      facilitated retention of a T-maze left-right discrimination, and speeded up
      acquisition of concurrent discrimination in a radial maze. These effects were
      consistent across successive experiments with a dose of 10mg/kg; lower doses (2.5
      and 5.0mg/kg) had less or no effect depending on the task. These results,
      together with theoretical considerations, led us to investigate the effect of
      tianeptine on the sequential-specific alternation deficit induced by long-term
      ethanol administration in the same strain of mice. Results showed that, at the
      dose of 10mg/kg, the drug completely alleviated the alcohol-induced deficit.
      Unlike tianeptine, fluoxetine impaired discrimination performance in the radial
      maze. These data are discussed in light of the effects of tianeptine on
      serotonergic transmission and of the role of serotonin and acetylcholine in
      learning and memory processes.

PMID- 11224047
TI  - Ethanol decreases responding on behavior maintained under concurrent schedules of
      both positive reinforcer presentation and avoidance in humans.
AB  - Six human volunteers were tested during 15min sessions under the behavioral
      contingencies of a concurrent fixed-ratio, fixed-ratio schedule of point-gain
      reinforcement and point-loss avoidance. Completion of each fixed-ratio 50 (FR 50)
      on the point-gain lever produced 10 points, which were exchanged for money ($.01
      per point) after each week of the study. Point losses of 10 points were scheduled
      to occur during the session on a variable-time 60sec schedule. The total amount
      of money accumulated was continuously displayed on video monitor. Subjects were
      exposed to the concurrent schedule until responding under the schedules of point
      gain and point loss stabilized. After responding had stabilized under these
      contingencies (4-5 sessions), subjects were tested each day 30min following
      administration of ethanol, in doses of 0.32, 0.64 or 0.96g/kg, or placebo.
      Ethanol decreased responding in all subjects and produced dose-related decreases
      in overall response rates in three subjects. These effects were not related to
      self-reported current alcohol consumption. Response rates on the reinforcement
      and the avoidance schedules were both decreased by ethanol. Thus, under these
      conditions, behavioral effects of ethanol on concurrent FR responding did not
      depend on the nature of the consequent event.

PMID- 11224048
TI  - The effects of NMDA antagonists on punished exploration in mice.
AB  - Previous studies have reported that several NMDA antagonists show anxiolytic-like
      activity in behavioural tests. To follow up the observation that AP7 increased
      the punished exploration of mice in the four plate test, several NMDA antagonists
      were tested in this procedure in shocked and non-shocked conditions. AP7
      increased shocked exploration without increasing non-shocked exploration.
      However, another competitive NMDA antagonist, CGS 19755, produced no increases in
      exploration in either condition. The non-competitive antagonists, phencyclidine,
      MK-801 and dextromethorphan, produced dose-related increases in activity in both
      the non-shocked and shocked conditions. This effect is probably best considered a
      psychomotor stimulant action rather than an anxiolytic-like activity. The non
      competitive NMDA antagonist, SL 82.0715, which acts at the polyamine site, and
      the ethyl ester of 7-chlorokynurenic acid, which acts at the glycine modulatory
      site, produced only decreases in exploration indicating that they lack both
      stimulant and anxiolytic activity. Although providing little evidence for
      anxiolytic action the present results further demonstrate that compounds acting
      at different sites within the NMDA receptor complex can give rise to very
      different pharmacological and behavioural effects.

PMID- 11224049
TI  - Extinction procedures abolish conditioned stimulus control but spare sensitized
      responding to amphetamine.
AB  - The effect of extinction on previously established environment-specific
      sensitization of the locomotor activating effects of 1.0mg/kg d-amphetamine
      sulfate was studied in an attempt to investigate the relation between
      sensitization and conditioning of the drug effect. During the conditioning phase,
      groups of eight rats each were administered drug, i.p., prior to being placed in
      activity boxes and saline in their home cages (paired group), drug in the home
      cages and saline in the activity boxes (unpaired group), or saline in both
      environments. Evidence for conditioning and environment-specific sensitization
      was found following the conditioning phase in tests during which animals were
      administered saline or amphetamine, respectively. On a final test for environment
      specific sensitization that followed the extinction phase (during which all
      animals received saline injections in both the activity boxes and the home
      cages), sensitized responding to amphetamine was found in both the paired and
      unpaired groups, suggesting that prior to extinction the expression of
      sensitization in the unpaired group had been under inhibitory control.

PMID- 11224050
TI  - 5-HT mediation of the antiaversive effect of isamoltane injected into the dorsal
      periaqueductal grey.
AB  - A previous study from this laboratory reported an antiaversive effect of the beta
      adrenoceptor blocker propranolol microinjected into the dorsal periaqueductal
      grey (DPAG) of the rat, that was antagonized by the 5-HT(2) receptor blocker
      ritanserin. The present results show that microinjection into the DPAG of
      isamoltane (4-32nmol) a beta-blocking agent that binds to 5-HT(1B) receptors more
      selectively than propranolol, raised the threshold of aversive electrical
      stimulation of the rat DPAG in a dose-dependent manner. The antiaversive effect
      of 8nmol of isamoltane was antagonized by pretreatment with ritanserin (10nmol),
      as well as by the more selective 5-HT(2) receptor blocker ketanserin (10nmol).
      Therefore, the antiaversive effect of beta-adrenoceptor/5-HT(1B) receptor
      antagonists injected into the DPAG is likely to be mediated by endogenous 5-HT,
      through activation of 5-HT(2) receptors.

PMID- 11224051
TI  - The discriminative stimulus effects of MK-801 in pigeons.
AB  - The discriminative stimulus effects of MK-801 [(+)-5-methyl-10, 11-dihydroxy-5H
      dibenzo (a,d) cyclohepten-5, 10-imine], a proposed noncompetitive N-methyl-D
      aspartate (NMDA) antagonist, were studied in pigeons discriminating MK-801 from
      saline, responding being maintained by food. Compounds with noncompetitive NMDA
      antagonist effects in other preparations (PCP [0.18-5.6mg/kg], dextrorphan [1
      32mg/kg], ketamine [1-32mg/kg] and dexoxadrol [1-10mg/kg]) produced MK-801
      appropriate responding dose-dependently. The potency order for this effect, and
      for response rate decreasing effects, closely mirrored the potency order for
      these compounds in causing catalepsy, an effect believed to be mediated by
      antagonism at the NMDA receptor complex. NMDA (0.32-5.6mg/kg), morphine (1
      10mg/kg) and pentobarbital (1-17.8mg/kg) produced almost no MK-801-appropriate
      responding. There were no consistent potency differences among the (+)-isomer (1
      32mg/kg), the (-)-isomer (1-17.8mg/kg) and the racemate (1-17.8mg/kg) of SKF
      10,047 in producing MK-801-appropriate responding. The competitive NMDA
      antagonist CGS 19755 (1-10mg/kg) produced partial MK-801-appropriate responding
      (maximum value = 77.8%) up to 8h after administration. The homogeneity of the
      discriminative stimulus effects among compounds with noncompetitive NMDA
      antagonist effects in vitro, as well as the partial substitution for MK-801 by
      CGS 19755, suggest that the MK-801 discriminative stimulus in pigeons is due to
      noncompetitive NMDA antagonism.

PMID- 11224052
TI  - Ethanol-like discriminative stimulus effects of non-competitive n-methyl-d
      aspartate antagonists.
AB  - The discriminative stimulus effects of noncompetitive N-methyl-D-aspartate (NMDA)
      receptor antagonists were investigated in animals trained to discriminate 1.5g/kg
      (pigeons) or 1.25g/kg (mice) ethanol from vehicle. Key-pecking of pigeons and
      lever responding of mice were maintained under fixed ratio schedules of mixed
      grain or milk reinforcement, respectively. Phencyclidine (PCP) and ketamine dose
      dependently substituted for the ethanol stimulus in both species, with PCP being
      about 10-fold more potent than ketamine. In pigeons, PCP and ketamine fully
      substituted for ethanol at doses that did not significantly alter rates of
      responding; with mice, complete substitution was accompanied by response rate
      decreasing effects. In pigeons, the highly selective NMDA receptor/ionophore
      antagonist MK-801 also substituted for ethanol at a dose that was accompanied by
      reduced response rates. Compounds that did not substitute for the ethanol
      stimulus were cocaine (both species), the 5-HT(1B) receptor agonist TFMPP
      (pigeon), the H(1) receptor antagonist hydroxyzine (mice), and the
      anticonconvulsants phenytoin and ethosuximide (mice). The present data show that
      PCP-like drugs that are antagonists of NMDA receptor-mediated neurotransmission
      share common discriminative stimulus effects with ethanol.

PMID- 11224053
TI  - Attenuation of the rate-altering effects of cocaine by magnesium chloride in
      squirrel monkeys.
AB  - Three adult male squirrel monkeys that were trained to respond on a 3-min fixed
      interval schedule of food reinforcement were injected with various doses of
      magnesium chloride (MgCl(2), 30 and 100mg/kg), cocaine (0.03-3.0mg/kg), and their
      combination. The purpose of the study was to determine if MgCl(2) could alter the
      rate of responding and if it could alter the rate-increasing and rate-decreasing
      effects of cocaine. MgCl(2) had little effect on responding during the 2h
      sessions. Low doses of cocaine (0.03-0.1mg/kg) were ineffective, intermediate
      doses (0.1-1.0mg/kg) increased responding, and high doses (1.0-3.0mg/kg)
      decreased responding. When MgCl(2) was combined with intermediate doses of
      cocaine, the rate-increasing effects of cocaine were attenuated. Less reliably,
      increased rates of responding were sometimes observed when MgCl(2) was combined
      with low (ineffective) or high (rate-decreasing) doses of cocaine. These
      interactions depended both on the time following injection and the dose of
      MgCl(2) and showed marked individual differences. These effects observed in
      monkeys are similar to some of the interactions previously reported in rodents.

PMID- 11224054
TI  - Dual activation by lisuride of central serotonin 5-HT(1A) and dopamine D(2)
      receptor sites: drug discrimination and receptor binding studies.
AB  - To investigate central serotonergic (5-HT) and dopaminergic (DA) actions of
      lisuride, the discriminative properties of lisuride (0.05mg/kg, i.p.) in rats
      were investigated, in addition to the radioligand binding of the compound to 5-HT
      and DA receptor subtypes. Lisuride was found to possess high affinities for 5
      HT(1A) receptor sites (Ki=0.5nM) and D(2) receptor sites (Ki=2.0nM). The
      autoradiographic binding pattern of 4nM [(3)H]lisuride in rat brain showed high
      densities of sites displaceable by the 5-HT(1A) agonist 8-OH-DPAT in hippocampus,
      lateral septal nucleus and amygdala, as well as those displaceable by the D(2)
      antagonist sulpiride in striatum, nucleus accumbens and olfactory tubercle. In
      drug discrimination tests, the mixed, D(1)/D(2) agonist apomorphine, the partial
      D(2) receptor agonists (-)-3-PPP and terguride and the 5-HT(1A) agonist 8-OH-DPAT
      substituted for lisuride. The D(1) agonist SKF38393, the D(1) antagonist
      SCH23390, the D(2) antagonist sulpiride, the 5HT(1B) agonist m-CPP and the 5
      HT(2) agonist DOI were not generalized to the lisuride cue. In antagonism tests,
      the D(2) antagonist haloperidol and the 5-HT antagonist methysergide both induced
      partial but significant antagonism to the lisuride cue, but the D(1) antagonist
      SCH23390 did not. These results indicate that discriminative stimulus properties
      of lisuride are mediated by the dual activation of 5-HT(1A) and D(2) receptor
      sites in brain.

PMID- 11224055
TI  - Differential effects of d-fenfluramine, l-fenfluramine and d-amphetamine on the
      microstructure of human eating behaviour.
AB  - An observational technique, demonstrated to provide reliable data under a variety
      of conditions, was used to evaluate the effects of d-fenfluramine, l
      fenfluramine, d-amphetamine, and fenfluramine-amphetamine combinations on eating
      behaviour in human subjects. Following an overnight fast, subjects ate lunch from
      a dispenser allowing free access to a choice of ten sweet and savoury foods, of
      varying macronutrient composition. D-fenfluramine (30mg) and d-amphetamine (15mg)
      reduced food intake; l-fenfluramine (30mg) was essentially inactive. The net
      effects of d-fenfluramine and d-amphetamine on food intake were additive, but the
      behavioural mechanisms of action were different for the two drugs. D-amphetamine
      decreased the duration of the meal, as well as the time spent chewing or
      manipulating food and the number of bites, but had no effect on eating rate; by
      contrast, d-fenfluramine decreased the rate of eating, but had no effect on meal
      duration.

PMID- 11224056
TI  - The effects of compounds acting at the benzodiazepine receptor complex on the
      ultrasonic calling of mouse pups.
AB  - The influence of a range of drugs acting at the benzodiazepine - GABA receptor -
      chloride ion complex on the ultrasonic calling of mouse pups was examined. Five
      benzodiazepine agonists decreased, and four inverse agonists increased, the rate
      of calling; both effects were blocked by the benzodiazepine antagonist RO 15
      1788. Muscimol and baclofen, that act via the GABA receptor, both decreased
      calling, whereas pentylenetetrazole that directly affects the chloride channel
      increased the rate of calling. It was concluded that the monitoring of ultrasonic
      calling is a useful means of screening for the effects of benzodiazepines.

PMID- 11224057
TI  - Anatomical substrates for neuroleptic-induced reward attenuation and neuroleptic
      induced response decrement.
AB  - Rats were implanted with bilateral indwelling cannulae, in the nucleus accumbens
      (NAS), anterodorsal striatum (ADS) or basolateral amygdala (BLA). Administration
      of sulpiride to the NAS reduced spontaneous locomotion, caused a time-independent
      suppression of lever pressing on a random-interval 30sec schedule of food
      reinforcement, and reduced preference for a weak 0.7% sucrose solution over water
      without affecting the total volume of fluid consumed. Administration of sulpiride
      to the ADS did not affect spontaneous locomotion, but caused a time-dependent
      response decrement in both operant behaviour and consumption of 0.7% sucrose.
      Administration of sulpiride to the BLA had no effect in any of these tests.
      However, at all three infusion sites, sulpiride increased the consumption of a
      34% sucrose solution. The data suggest a preferential involvement of the
      mesolimbic dopamine system in neurolepticinduced attenuation of reinforcer value,
      and a primary role of the nigrostriatal dopamine system in neuroleptic-induced
      time-dependent response decrements.

PMID- 11224058
TI  - Methocarbamol: evaluation of reinforcing and discriminative stimulus effects.
AB  - The behavioural effects of methocarbamol, a centrally acting muscle relaxant,
      were assessed using self-injection procedures in baboons and drug discrimination
      procedures in baboons and rats. The ability of methocarbamol to maintain self
      injection was examined using a drug substitution procedure. Responding was
      maintained initially by cocaine delivery (0.32mg/kg/injection, i.v.). Each drug
      injection was followed by a 3-h timeout allowing a maximum of eight injections
      per day. Methocarbamol doses or vehicle were substituted for cocaine for a period
      of 15 or more days each, with re-establishment of responding under cocaine after
      each substitution. Evaluation of a wide range of methocarbamol doses (1.0
      32mg/kg/injection) showed that this compound maintained rates of self-injection
      at vehicle control levels, which were below those maintained by cocaine. The
      discriminative stimulus effects of methocarbamol were studied in baboons trained
      to discriminate either lorazepam (1.8mg/kg, p.o.) or pentobarbital (10.0mg/kg,
      p.o.) from the no-drug condition and in rats trained to discriminate lorazepam
      (1.0mg/kg, i.p.), diazepam (1.0mg/kg, i.p.), or pentobarbital (10.0mg/kg, i.p.)
      from the no-drug condition using a two-lever, food-maintained drug discrimination
      procedure. Evaluation of a range of doses in baboons (10-180mg/kg, p.o.) and rats
      (32-180mg/kg, i.p.) showed that methocarbamol did not occasion drug-lever
      responding at any dose. Methocarbamol did not produce changes in response rates
      in baboons, but higher doses severely suppressed response rates in rats. The
      present experiments show that the behavioral profile of methocarbamol is clearly
      distinguishable from that of barbiturates and benzodiazepines. Taken together
      with analogous studies with other sedative-anxiolytic drugs, these results
      suggest that methocarbamol has a relatively low likelihood of abuse.

PMID- 11224059
TI  - Blockade of the discriminative stimulus effects of cocaine in rhesus monkeys with
      the D(1) dopamine antagonists SCH-39166 and A-66359.
AB  - Rhesus monkeys were trained in a 2-lever, food-reinforced drug discrimination
      paradigm to discriminate cocaine (0.2 or 0.4mg/kg, i.m., 10min pre-session) from
      saline. Before test sessions, in which responding on either lever was reinforced,
      the monkeys were injected with various doses of cocaine alone or in combination
      with the D(1) dopamine antagonists SCH-39166 or A-66359. Administration of
      cocaine alone (0.025-0.4mg/kg, i.m.) resulted in a dose-related increase in the
      percent of responses that occurred on the drug-appropriate lever. Both SCH-39166
      (0.05-0.1mg/kg, i.m., 60min pre-session) and A-66359 (0.2-0.4mg/kg, i.m., 30min
      pre-session) reduced cocaine-appropriate responding from more than 80% to less
      than 20% at least at one dose combination in all monkeys. Also for both drugs and
      in all monkeys, the blockade was overcome by increasing the dose of cocaine. SCH
      39166 was more potent and longer acting than A-66359. The results provide further
      evidence that D(1) dopamine receptors are involved in the discriminative stimulus
      effects of cocaine and that D(1) antagonists may block the subjective effects of
      cocaine.

PMID- 11224060
TI  - Effects of NMDA antagonists on memory processes in a novel two-trial swimming
      test.
AB  - Rats were placed in a circular swimming pool for two 3-min swims separated by 3
      days. In the first swim control rats swam initially around the perimeter of the
      pool and later spent more time in the central region and swam more slowly. The
      time spent in the centre during min 1 was much higher in the second swim than in
      the first. This alteration of behaviour by the previous experience suggests that
      a memory of the first swim was formed. The NMDA antagonists, CPP (10-20mg/kg) or
      MK-801 (50-100ug/kg), administered before the first swim attenuated or reversed
      the decline in swimming speed and attenuated the intra-trial increase in the time
      spent in the centre. The alteration of swimming pattern between the two swims was
      also reduced. Administering the antagonists immediately after the first swim did
      not have this effect. Drug administration shortly before the second swim
      prevented the within-trial decline of swimming speed, but did not significantly
      reduce the high proportion of time spent in the central region during min 1. The
      results suggest that in this paradigm NMDA receptors are involved in within-trial
      habituation of swimming activity and in the initial stages of long-term memory
      formation, but are not involved in memory consolidation or retrieval.

PMID- 11224061
TI  - Discriminative stimulus properties of the benzodiazepine receptor partial agonist
      beta-carbolines abecarnil and ZK 95962: a comparison with chlordiazepoxide.
AB  - Separate groups of rats were trained to discriminate one of three benzodiazepine
      receptor ligands from vehicle. The three ligands used, the benzodiazepine
      chlordiazepoxide, and the beta-carboline partial agonists ZK 95962 and abecarnil,
      have been reported to have different agonistic profiles. All three ligands formed
      specific benzodiazepine-receptor mediated discriminative stimuli antagonizable by
      at least one benzodiazepine antagonist. Different patterns of generalization were
      observed for each cue. As reported previously full and partial agonists
      substituted for chlordiazepoxide, whereas generalization to ZK 95962 was obtained
      more readily with partial agonists and antagonists with weak partial agonist
      activity. In contrast to the other two cues, the abecarnil discriminative
      stimulus was difficult to train and was unstable over time. Additionally, the
      abecarnil cue showed commonalities only with sedative or BZ1 receptor agonists.
      These results demonstrate qualitative differences between different
      benzodiazepine receptor ligands dependent on the intrinsic activity of the
      compound used.

PMID- 11224062
TI  - Involvement of dopamine uptake in the discriminative stimulus effects of cocaine.
AB  - The involvement of dopaminergic and adrenergic mechanisms in the stimulus effects
      of cocaine was studied in rats trained to discriminate cocaine from saline. The
      cocaine (10mg/kg) cue generalized to compounds that act primarily by inhibiting
      DA uptake with an order of potency of nomifensine (ED(50) = 0.38mg/kg) > GBR12909
      (1-{2-[bis(4-fluorophenyl) methoxy]-ethyl]}-4(3-phenylpropyl) piperazine (ED(50)
      = 4.38mg/kg) > bupropion (ED(50) = 11.6mg/kg) but not to those that: (1) directly
      activate postsynaptic DA receptors (bromocriptine), (2) release DA (amantadine),
      (3) have antagonist actions at presynaptic DA receptors (cis-flupenthixol) or,
      (4) inhibit the uptake of NE (desipramine, imipramine, nisoxetine). When given in
      combination with cocaine, the D2 receptors antagonist (-)sulpiride had no
      significant effects on cocaine-lever selection. These results suggest that
      inhibition of DA uptake is involved in the discriminative stimulus properties of
      cocaine since, (1) compounds that act by inhibiting DA uptake rather than through
      some other mechanism mimic cocaine and, (2) the reported affinities of these
      drugs for the DA transport site and their order of potency in blocking cocaine
      are identical.

PMID- 11224063
TI  - Effects of circadian cycle and time of testing on drug-induced anorexia in rats.
AB  - Based on the results from a previous study conducted in our laboratory, the
      present experiment sought to replicate the finding that the magnitude of the
      anorexic effect of phenylpropanolamine (PPA) in rats is greater during the early
      dark phase than the early light phase of the circadian cycle. Moreover, the
      present study included two additional anorectic drugs, amphetamine and
      fenfluramine, as well as additional testing times in the middle of the respective
      phases of the circadian cycle. For the 1h feeding tests, all three anorectic
      drugs demonstrated a significant dose-dependent phase (Light/Dark) effect such
      that all three agents induced greater anorexia during the dark phase. The
      significance of the dark phase testing was also apparent after 4h of testing for
      PPA and amphetamine, but not for fenfluramine. Furthermore, during the 1h tests,
      PPA and amphetamine, but not fenfluramine, demonstrated significant test time
      interactions such that the greatest magnitude of anorexia was observed during the
      middle of the dark phase. The present data are intriguing in that the anorexic
      effects of these three drugs, which are believed to operate via three distinct
      neurochemical mechanisms, are modulated by the circadian cycle in a similar
      fashion during a 1 h feeding trial. Thus, the results of this study indicate that
      one salient factor (i.e. time of testing within the circadian cycle) may, in
      part, contribute to the variability often observed in feeding studies using
      different experimental protocols.

PMID- 11224064
TI  - Social competition in rats: a test sensitive to acutely administered anxiolytics.
AB  - Male Wistar rats were housed in groups of three (triads) and given brief sessions
      during which sweetened milk was available in a drinking bottle. The rats showed
      intense competition to obtain access to the milk and in many groups a stable rank
      order was formed of a dominant, an intermediate and a subordinate rat, when
      assessed as the amount of access to the drinking tube. When the subordinate rats
      were injected with the anxiolytic drugs chlordiazepoxide (1.25-20mg/kg),
      buspirone (0.3-5.0mg/kg) and alpidem (2.5-20mg/kg) and low doses of the hypnotic,
      zolpidem (0.125-2.0mg/kg) they increased their access to the milk. These
      increases were generally at the expense of the dominant rats whose access
      decreased. The effect of alpidem (5mg/kg) was antagonized by flumazenil
      (10mg/kg). Increases in access in subordinate rats were not seen after
      haloperidol (0.025-0.2mg/kg), imipramine (5, 10mg/kg) or morphine (2.5-10mg/kg).
      As the anxiolytic drugs were active at relatively low doses this test of social
      competition may provide a particularly sensitive and selective procedure for
      detecting and evaluating the actions of drugs from this class.

PMID- 11224065
TI  - Pre-weaning non-handling of rats disrupts latent inhibition in males, and results
      in persisting sex- and area-dependent increases in dopamine and serotonin
      turnover.
AB  - Pre-weaning "handling" of rat pups (1-21 days) is reported to result in a number
      of behavioural differences from "nonhandled" pups, persisting into adult life. In
      general, these are associated with altered emotional reactivity. We now report
      the results of a replication of a previous finding that handling also affects
      performance on a latent inhibition (LI) task, which involves learning in the
      absence of motivation. The effect of 30 pre-exposures to a tone stimulus on the
      formation of an association from two pairings between that stimulus and footshock
      was determined. The association was indexed by the suppression of licking
      resulting from tone presentation during licking for water reward. In adult female
      rats, pre-exposure prevented the formation of this association (i.e. LI was
      present) whether they had been handled or nonhandled pre-weaning. However in
      adult males, pre-exposure was effective only in handled rats, and not in
      nonhandled. This confirms the striking pattern of results reported previously by
      another group (Weiner et al., 1987). The turnover of dopamine (DA) and serotonin
      was subsequently determined post mortem from the ratios of metabolites to amines
      in DA-innervated brain areas of the rats used in the present study. Pre-weaning
      nonhandling and female sex, were independently associated with increased dopamine
      turnover, and to a lesser extent with increased serotonin turnover. While these
      increases were not sex-specific, nonhandled males did show a pattern of increased
      DA turnover relative to serotonin turnover in limbic areas; previous
      pharmacological and physiological studies support the idea that this pattern may
      be associated with impairment of LI. It is concluded that preweaning nonhandling
      is indeed associated with an impairment of LI restricted to males, and is
      associated with enduring changes in DA and 5HT turnover in both sexes. Further
      studies are indicated to determine the precise role of these changes in the
      behavioural effects of pre-weaning nonhandling.

PMID- 11224066
TI  - A unique enhancement of associative learning produced by
      methylenedioxyamphetamine.
AB  - The effects of methylenedioxyamphetamine (MDA) on classical conditioning of the
      rabbit's nictitating membrane response were assessed in four experiments.
      Experiment 1 established a dose-effect curve for MDA doses of 0, 1, 3, and
      10umol/kg. Both the 3 and 10umol/kg doses significantly enhanced the rate of
      learning. Experiment 2 established that the 10umol/kg dose of MDA had no effect
      on non-associative determinants of responding to the conditioned stimulus (CS).
      However, this dose of MDA apparently sensitized the response to the unconditioned
      stimulus (US). Experiments 3 and 4 assessed the effects of the 10umol/kg dose of
      MDA on sensory processing of the CS and US, respectively. MDA had no effect on
      the intensity thresholds for eliciting responses to either of these stimuli.
      Thus, the enhanced rate of acquisition observed in experiment 1 cannot be
      attributed to an increase in nonassociative responding to the CS or to enhanced
      sensory processing of the CS or US. MDA apparently enhanced the rate of
      acquisition in experiment 1 by facilitating the association between the CS and
      US. These findings are unique in that no other hallucinogen we have examined has
      enhanced acquisition without also affecting either non-associative responding or
      sensory processing of the CS and US.

PMID- 11224067
TI  - Terguride, a dopamine D(2) partial agonist, as a discriminative stimulus in rats.
AB  - Drug discrimination training with terguride, a 9, 10-transdihydrogenated
      derivative of lisuride, was carried out using a two-lever food-reinforced
      procedure (FR 10) in rats, to investigate its influence on central dopaminergic
      (DA) and serotonergic (5-HT) functions. The terguride (0.05mg/kg, i.p.)
      discrimination was established within 64 +/- 5 training sessions (mean +/- S.E.)
      and was stably maintained thereafter. Higher doses of terguride could not be used
      for discriminative training due to response disruption. In generalization tests
      with terguride, drug-appropriate responding increased dose-dependently and
      reached levels of 45 and 99% at 0.01 and 0.05mg/kg i.p. The D(2) agonist lisuride
      at low doses and the DA autoreceptor agonist (-)-3-PPP substituted for terguride.
      The DA agonist apomorphine and the 5-HT agonist 5-MeO-DMT produced dose-dependent
      but incomplete substitution. The D(1) agonist SKF38393, the DA antagonist
      haloperidol, the D(2) antagonist sulpiride, the D(1) antagonist SCH23390, the 5
      HT(1A) agonist 8-OH-DPAT, the 5-HT(1B) agonist m-CPP and the 5-HT(2) agonist DOI
      were not generalized. In antagonism tests, sulpride completely blocked the
      terguride-appropriate response, but SCH23390 and the 5-HT antagonist methysergide
      did not. These results indicate that discriminative stimulus properties of
      terguride in rats are mediated primarily by activation of receptors with
      characteristics similar to those of presynaptic D(2) autoreceptors.

PMID- 11224068
TI  - Behavioural aspects of drug discrination.

PMID- 11224069
TI  - Historical context of state dependent learning and discriminative drug effects.
AB  - Drug-induced state dependent learning (SDL), as well as similar effects on memory
      retrieval exercised by physiological states, have been known since 1830. Before
      1950, understanding of this area derived primarily from clinical descriptions of
      somnambulism, dream recall, fugue states, and cases of multiple personality.
      After 1950, experimental demonstrations of the properties of SDL and drug
      discriminations (DDs), along with a series of changes in the DD procedure, have
      led to the DD paradigm that is currently employed, and which has properties that
      make it an extremely useful tool for preclinical investigation of a variety of
      pharmacological and psychological questions. These conceptual and technical
      developments have resulted in widespread acceptance of the DD paradigm as a
      preclinical research method. This paper reviews the nineteeth and twentieth
      century history of clinical observations, concepts, and experiments, that have
      led to our current status of knowledge about drug discriminations and SDL.

PMID- 11224070
TI  - Measures of stimulus generalization in drug discrimination experiments.
AB  - Different approaches to measuring stimulus generalization in drug discrimination
      experiments are compared. The main issue, with implications for interpreting
      partial generalization, has been whether it is preferable to use graded or
      quantal indices. The first step is to determine whether discriminative drug
      effects are inherently quantal or graded; it would be pointless to attempt to
      assess a quantal phenomenon with a graded index. Evidence is reviewed suggesting
      that behavioural variables, and possibly pharmacological variables as well,
      determine the nature of the effects. Certain experiments used to evaluate the
      nature of generalization with exteroceptive stimuli have yet to be applied to the
      interoceptive stimuli that drugs produce. However, like many other attributes of
      drug action, discriminative stimulus effects are not immutable in nature, but are
      malleable and influenced by variables such as the schedule of reinforcement.
      There appears to be a potential for selecting procedures that generate graded
      responding in order to maximise precision. This ideal situation has yet to be
      fully realised in practice since the optimal conditions for generating graded
      responding remain to be identified, and present indices, based on percentage
      scores, do not generate interval scales of measurement. Until these issues are
      resolved, there is no case for maintaining that measurements of discriminative
      drug effects should with advantage be always quantal or always graded; either
      approach is compatible with research of high quality and can generate valid
      results and conclusions.

PMID- 11224071
TI  - The discriminative response: an elementary particle of behavior Commentary on
      Stolerman "Measures of stimulus generalization in drug discrimination
      experiments"

PMID- 11224072
TI  - The time is ripe for an experimental analysis of measurement issues Commentary on
      Stolerman "Measurement issues in drug discrimination"

PMID- 11224074
TI  - Subjective drug effects in context Commentary on Preston and Bigelow "Subjective
      and discriminative effects of drugs"

PMID- 11224073
TI  - Subjective and discriminative effects of drugs.
AB  - Human research using drug discrimination procedures is reviewed. Originally
      developed in the animal laboratory, drug discrimination procedures have been
      suggested to provide an index of subjective drug effects. Human research provides
      unique opportunities to assess the relationship of subjective and discriminative
      drug effects, since only in humans can the two be assessed concurrently. Methods
      used for assessing subjective effects and methods used for training and assessing
      drug discriminations in humans are described. Research data are then reviewed and
      discussed with respect to what they suggest concerning the relationship of
      subjective and discriminative drug effects to one another. It is concluded that
      there is a relationship, though not a simple one, and that the nature of the
      relationship is likely to be influenced by the procedural details of specific
      drug discrimination training and testing paradigms. Recommendations for future
      research are made.

PMID- 11224075
TI  - Human drug discrimination: current limitations, future possibilities Commentary
      on Preston and Bigelow "Subjective and discriminative effects of drugs"

PMID- 11224076
TI  - A demonstration of the graded nature of the generalization function of drug
      discrimination learning within the conditioned taste aversion procedure.
AB  - Although control of discriminative performance will often generalize to different
      doses of the training drug or to drugs from the same class as the training drug,
      the nature of this generalization is unknown. Prior work has suggested that the
      generalization is primarily quantal in nature with animals displaying either
      vehicle-appropriate or drug-appropriate responding, depending upon their
      detection of the drug stimulus. It has been questioned whether this quantal
      nature of generalization reflects a characteristic response to drug stimuli or
      whether such responding is a function of the specific training and testing
      procedures used to establish and measure drug discrimination learning. The
      present paper evaluated this issue by analyzing the generalization functions of
      individual subjects trained and tested within one specific drug discrimination
      procedure, i.e. the conditioned taste aversion design. Responding within this
      design was generally graded. It is clear that quantal responding is not a
      necessary outcome of drug generalization assessments and that the nature of
      generalization in drug discrimination learning is a function of the specific
      procedure utilized in training and testing the discrimination. The results of the
      present analysis are discussed in terms of other recent work reporting graded
      functions.

PMID- 11224077
TI  - Discriminated taste aversion with a 5-HT(1A) agonist measured using saccharin
      preference.
AB  - Rats were trained to discriminate the stimulus properties of the selective 5
      HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.4mg/kg i.p.)
      versus saline, using a discriminated taste aversion procedure. Tests of stimulus
      generalization and drug substitution were conducted using two-bottle choice tests
      between saccharin and water. Rats that received pairings of 8-OH-DPAT with LiCl
      demonstrated significant reductions of saccharin preference when administered 8
      OH-DPAT at doses of 0.1mg/kg or higher. 8-OH-DPAT did not alter saccharin
      preference significantly in controls that did not receive LiCl injections. Other
      drugs with high affinity for 5-HT(1A) receptors, such as the azapirones gepirone,
      ipsapirone and buspirone, produced selective reductions of saccharin preference
      in rats trained to discriminate 8-OH-DPAT from saline but not in controls. Three
      drugs with low affinity for 5-HT(1A) receptors, the benzodiazepine anxiolytic
      diazepam, d-amphetamine, and a common metabolite of the azapirones 1-(2
      pyrimidinyl) piperazine (1-PP) altered fluid intake significantly but failed to
      produce significant changes in saccharin preference in either the discrimination
      or control groups. This study indicates that two-bottle preference tests can be
      used to measure the stimulus properties of 8-OH-DPAT trained using a
      discriminated taste aversion procedure, because the stimulus effects of drugs,
      measured using saccharin preference, can be separated from the nonspecific
      effects of drugs on fluid consumption.

PMID- 11224078
TI  - Dose-related caffeine discrimination in normal volunteers: individual differences
      in subjective effects and self-reported cues.
AB  - A within subject design was used to study a caffeine versus placebo drug
      discrimination in five volunteers who were not explicitly instructed that the
      drug conditions involved caffeine and placebo. The caffeine (200 or 300mg) versus
      placebo discrimination was acquired by all subjects and remained stable (78-90%
      accuracy) throughout the study which spanned 5 to 8.7 months across the subjects.
      A full caffeine dose-response function (50 to 400 or 600mg) was determined
      repeatedly under test conditions in each subject; caffeine produced orderly dose
      related increases in caffeine identification in all subjects. The present study
      evaluated individual subject data to examine the correspondence between the
      subjective effects of caffeine versus placebo and the cues subjects reported as
      being important to making the discrimination. Although the subjective effects and
      self-reported cues differed across subjects, there was a correspondence within
      subjects. Prominent self-reported cues for caffeine included
      jittery/nervous/anxious (four subjects) and alert/active (one subject); self
      reported cues for placebo included tired and/or headache (three subjects) and
      absence of drug effect (two subjects). The reporting of tired and headache as
      cues for the placebo condition suggests that caffeine withdrawal may produce
      stimulus effects relevant to the caffeine versus placebo discrimination.

PMID- 11224079
TI  - Further studies on the discriminative stimulus effects of diazepam in humans.
AB  - Twelve normal humans were trained to discriminate between 10mg diazepam (DZ) and
      placebo. Subjects reported to the laboratory for a total of 23 sessions. They
      filled out subjective effects questionnaires and ingested a capsule. They were
      then free to leave but filled out questionnaires 1, 3 and 6h later. During the
      first four sessions, the capsule was identified by letter code prior to
      ingestion. During the next seven sessions, the procedure was the same but the
      capsule was not identified. Six hours after receiving the capsule, subjects
      telephoned the experimenter to report their identification. When correct, they
      received a monetary bonus. Phase 3 consisted of 12 sessions including six
      additional training sessions. During the remaining sessions, subjects received
      capsules that contained test drugs. Seven of 10 subjects that completed the study
      were reliable discriminators. During phase 3, most subjects identified 25 and
      50mg tripelennamine, 0.125mg triazolam, and 5mg buspirone as placebo and these
      drugs produced few changes in mood. Triazolam at a dose of 0.25mg was identified
      as DZ by all subjects whereas 10mg buspirone was identified as DZ by 71%. DZ and
      0.25mg triazolam produced similar time-related changes on several subjective
      effects measures. Ten mg buspirone also produced changes in mood that were
      similar to those of DZ but usually of smaller magnitude and shorter duration.

PMID- 11224080
TI  - Modification of the discriminative stimulus effects of 8-OH-DPAT, buspirone and
      the beta-adrenoreceptor antagonist pindolol after chronic administration of the 5
      HT(1A) agonist 8-OH-DPAT in the pigeon.
AB  - The involvement of adrenoreceptor blocking drugs with the 5-HT(1A)-mediated
      discriminative stimulus was studied in pigeons trained to discriminate the 5
      HT(1A) receptor agonist 8-OH-DPAT (0.3mg/kg) from saline. Cumulative dose
      response curves were determined for 8-OH-DPAT, the beta-adrenergic antagonist
      pindolol, the alpha(1)-antagonist prazosin, as well as for the 5-HT(1A) agonist
      buspirone, before, during and after (8-OH-DPAT and pindolol) chronic
      administration of 8-OH-DPAT (3.0mg/kg/day for 6 weeks). The dose-response curves
      for 8-OH-DPAT and buspirone, which substituted for 8-OH-DPAT, were shifted to the
      left during chronic 8-OH-DPAT administration. Prazosin did not substitute for 8
      OH-DPAT at any time throughout the course of the study. Pindolol did not
      substitute for 8-OH-DPAT before chronic administration, but did so during and
      after 8-OH-DPAT was administered chronically. Chronic administration of 8-OH-DPAT
      resulted in a heightened sensitivity not only to the 5-HT(1A) agonists 8-OH-DPAT
      and buspirone, but also to what appear to be partial agonist effects of pindolol.
      This approach represents a first step in the in vivo characterization of changes
      in 5-HT(1A) sensitivity after chronic administration of 8-OH-DPAT using the drug
      discrimination procedure. This method may provide a useful behavioral model with
      which to investigate the mechanisms of anxiolytic and antidepressant effects of 5
      HT(1A) agonists and beta-adrenoceptor blocking drugs that only become apparent
      after 2 to 4 weeks of chronic administration.

PMID- 11224081
TI  - Attempts to establish phencyclidine and cocaine discrimination without error.
AB  - An attempt was made to train pigeons to discriminate phencyclidine (PCP) from
      saline using a three-key color-tracking procedure under which birds were trained
      under a second order schedule [FR10 (FR5)] "without errors." Training without
      errors was done by not lighting the side key on which responses were not
      reinforced during the early phases of discrimination training and then gradually
      increasing the light intensity on that key. Initially, this procedure prevented
      drug discrimination errors, but as the light intensity increased on the incorrect
      side key, errors began to appear and then surpassed the error rate of birds
      trained "with errors." When stimulus control stabilized, there were no
      differences in stimulus control by the phencyclidine stimulus as a function of
      the training procedure, as measured by error rates. Birds trained to discriminate
      PCP from saline with and without errors also showed no differences in the shape
      of the PCP stimulus generalization curve. A second attempt at training without
      errors under a second-order schedule was made in a second group of pigeons, using
      cocaine as the training drug and eliminating the use of the color-tracking
      procedure. The results were very similar to those with PCP. Few errors occurred
      in birds trained "without errors" until the incorrect key-light intensity was
      increased, at which time large numbers of errors began to occur, but ultimately
      differences in stimulus control as a function of the training procedure
      disappeared. There was no difference between birds trained with and without
      errors in the shape of the cocaine stimulus generalization curve. The pigeons
      trained to discriminate cocaine from saline under a second order FR 10 (FR 5)
      schedule showed complete generalization to d-amphetamine and partial
      generalization to phencyclidine and chlorpromazine. Because baseline stimulus
      control was deteriorating, the schedule was changed to a second order FR 4 (FR
      25) and stimulus control by cocaine was reestablished. Under this schedule,
      partial generalization was observed from cocaine to pentobarbital and
      chlorpromazine before baseline stimulus control weakened again. Both the broad
      generalization of the cocaine stimulus and the difficulty in maintaining stimulus
      control with cocaine have been observed by others; such data suggest that under
      some conditions the cocaine stimulus may lack specificity.

PMID- 11224082
TI  - Influence of some drugs of abuse on the discriminative stimulus properties of
      amphetamine.
AB  - The present study assessed the utility of a drug interaction paradigm for
      measuring the effects of various psychoactive drugs on the stimulus properties of
      d-amphetamine. In the first experiment, rats trained to discriminate 1.0mg/kg d
      amphetamine from saline were tested for generalization to a range of d
      amphetamine doses (0.25, 0.50 and 1.0mg/kg) injected alone or with cocaine,
      apomorphine or haloperidol. When given alone d-amphetamine yielded an orderly
      dose-response function and this was altered by the test drugs in a manner
      consistent with the dopamine agonist or antagonist actions of each compound. In
      the second experiment, the cueing effects of d-amphetamine were potentiated by
      nicotine and attenuated by morphine and midazolam. Ethanol enhanced the cueing
      effects of the lower d-amphetamine doses but produced no drug-lever responding
      when given alone. These findings confirm the results of previous studies which
      have assessed the effects of these classes of drugs on the stimulus properties of
      amphetamine. However, the results are inconsistent with the hypothesis that all
      drugs of abuse possess psychomotor stimulant properties.

PMID- 11224083
TI  - Discriminative stimulus effects of amphetamine and pentobarbitone separately and
      as mixtures in rats.
AB  - The discriminative effect of a mixture of (+)-amphetamine plus pentobarbitone was
      investigated to characterize behavioural control by a compound interoceptive
      stimulus. A two-bar drug discrimination procedure with food reinforcement was
      used. The role of training dose was assessed by keeping the dose of (+)
      amphetamine constant at 0.4mg/kg (SC) and progressively increasing that of
      pentobarbitone from 5mg/kg to 20mg/kg (SC). Initially stimulus control was
      attributable to (+)-amphetamine but as the dose of pentobarbitone was increased,
      stimulus control switched entirely to pentobarbitone. The reduced response to (+)
      amphetamine after training in compound with the larger doses of pentobarbitone
      was attributed to overshadowing of a relatively weak (+)-amphetamine stimulus by
      a more salient pentobarbital stimulus. There was partial generalization when
      either component drug was given at the same dose as in the mixture, and almost
      complete generalization at larger doses of each component; in contrast, there was
      little cross-generalization between (+)-amphetamine and pentobarbitone in rats
      trained with either drug alone. The findings suggested that components of the
      compound stimulus were perceived and processed separately rather than being
      blended into a new and distinct stimulus. Tests for generalization to quipazine,
      phencyclidine or morphine suggested that the compound stimulus produced by the
      mixture was no less specific than the stimuli produced by each of the component
      drugs. Rules governing discrimination of the abused mixture of (+)-amphetamine
      plus pentobarbitone appeared generally similar to those found in previous studies
      with non-abused mixtures of nicotine and midazolam.

PMID- 11224084
TI  - Cue dimensionality in the three-choice pentylenetetrazole-saline-chlordiazepoxide
      discrimination task.
AB  - Sprague-Dawley rats were trained in a three-choice drug discrimination task
      utilizing 5mg/kg chlordiazepoxide (CDP), saline (SAL), and 15mg/kg
      pentylenetetrazole (PTZ) as stimulus conditions. Generalization tests of the
      three training conditions resulted in exclusively injection-appropriate lever
      selection. Cross-generalization tests with PTZ or CDP resulted in dose-dependent
      lever selections confined to the training drug and SAL levers. Morphine and
      ethanol cross-generalization tests produced saline-appropriate responding,
      whereas cocaine and caffeine produced PTZ-appropriate responding at high doses.
      Tests conducted after concomitant administration of both training drugs
      demonstrated a reciprocal antagonism between the two drugs. More importantly,
      when the training dose of CDP was held constant and combined with increasing
      doses of PTZ, a shift from CDP- to PTZ-appropriate responding through a dose
      range of exclusive SAL-appropriate responding was demonstrated. Overt behavioral
      indices of seizure activity occurred at dose combinations that engendered only
      saline responding, but PTZ-appropriate responding did not correspond with the
      development of overt seizure episodes. These data suggest that the PTZ
      discriminative cue in the present three-choice paradigm is not primarily linked
      to its proconvulsant effects. The data are discussed in terms of an hypothesis in
      which the discriminable interoceptive cues for PTZ and CDP lie at opposite ends
      of a single continuum that has a neutral centroid, and this continuum more likely
      reflects an anxiolysis-anxiogenesis dimension than an anticonvulsant-seizure
      dimension.

PMID- 11224085
TI  - Reversal of a drug versus drug discrimination task with different exteroceptive
      conditions.
AB  - The effects of a change of an exteroceptive context (light and dark) on a drug
      vs. drug discrimination reversal task was investigated. Rats were trained to
      discriminate between either 1750mg/kg ethanol and 17.5mg/kg pentobarbital (high
      dose) or 1000mg/kg ethanol and 10.0mg/kg pentobarbital (low dose), using an
      electrified T-maze procedure. Once the initial acquisition had been acquired
      (phase I), the response requirements were reversed (phase II). For the
      experimental groups, this was accompanied by a change in exteroceptive conditions
      (light became dark and vice versa). For the control groups, the reversal phase
      was without any change in exteroceptive context. Finally, the animals were tested
      with saline and the training doses of the drugs, for both exteroceptive
      conditions. It was found that both original and reversal acquisition occurred
      faster in the high dose group. This is consistent with previous findings. There
      were no effects of a changed exteroceptive context on the speed of reversal
      learning, or on discriminative performance during final testing, in either dose
      group. A possible explanation is suggested for these findings.

PMID- 11224086
TI  - Discriminative stimulus properties of estradiol in male and female rats revealed
      by a taste-aversion procedure.
AB  - Gonadectomized male and female rats were trained to discriminate 50ug/kg
      estradiol-17B(E(2)) from its vehicle in a one-bottle forced-drinking
      discriminative taste-aversion procedure. The animals were injected SC with E(2)
      or arachidic oil, 60min prior to daily training sessions during which they had
      access to a saccharin (Sac) solution for 10min. Animals injected with E(2) prior
      to Sac-LiCl pairings and with arachidic oil prior to Sac-NaCl pairings acquired
      hormone discrimination, only suppressing Sac intake following the administration
      of E(2) and not following the administration of arachidic oil. Both males and
      females reliably discriminated E(2) from arachidic oil within 28 training
      sessions. Subsequent generalization tests revealed dose-dependent stimulus
      control of Sac intake by E(2) in both sexes (range of substitution doses: 0.4
      250ug/kg). The results show that E(2) may act as a discriminative stimulus in
      male and female rats.

PMID- 11224087
TI  - The discriminative stimulus effects of histamine H(1)-antagonists in pigeons.
AB  - Two groups of pigeons were trained to discriminate a histamine H(1)-antagonist
      (chlorpheniramine or promethazine) from saline with responding maintained under a
      fixed-ratio 30 schedule of food delivery. There was no cross-substitution with
      these two histamine H(1)-antagonists: that is, promethazine failed to substitute
      reliably for chlorpheniramine in chlorpheniramine-trained pigeons, and
      chlorpheniramine failed to substitute reliably for promethazine in promethazine
      trained pigeons. Among the other histamine H(1)-antagonists tested,
      tripelennamine consistently produced greater than 80% responding in
      chlorpheniramine-trained pigeons but not in promethazine-trained pigeons. In
      contrast, diphenhydramine consistently produced greater than 80% responding in
      promethazine-trained pigeons but not in chlorpheniramine-trained pigeons.
      Similarly, chlorcyclizine partially substituted for promethazine and failed to
      substitute for chlorpheniramine. d-Amphetamine substituted for chlorpheniramine
      in 2 of 4 pigeons and partially in a third pigeon, whereas d-amphetamine
      substituted for promethazine in only 1 of 4 pigeons. Pentobarbital failed to
      produce greater than 80% responding in either chlorpheniramine- or promethazine
      trained pigeons. The results of the present study demonstrate that the histamine
      H(1)-antagonists, chlorpheniramine and promethazine, have differential
      discriminative stimulus effects in pigeons. These findings suggest that the
      discriminative stimulus effects of this class of compounds are not based entirely
      on their ability to act as antagonists at histamine H(1)-receptors.

PMID- 11224088
TI  - Effects of the 5HT(1A) agonist anxiolytic gepirone on benzodiazepine withdrawal
      signs in rats.
AB  - The effects of gepirone at 3, 9 and 27mg/kg (b.i.d.) on benzodiazepine (BZ)
      withdrawal signs were studied in rats pretreated with chlordiazepoxide for 21
      days at doses up to 40mg/kg b.i.d. The BZ withdrawal indices studied were weight
      loss and anorexia. At 9 and 27, but not 3mg/kg (b.i.d.) gepirone potentiated the
      weight loss and anorexia seen during BZ withdrawal. These effects could not be
      attributed simply to high dose drug-induced "malaise" inhibiting food intake,
      since in drug-naive animals gepirone stimulated food intake and increased
      bodyweight. These data show clearly that gepirone potentiates BZ withdrawal
      signs. Similar findings have been reported recently in studies with ipsapirone
      (Goudie and Leathley, 1991). Such effects could be mediated by the a(2)
      adrenoceptor antagonist actions of 1-(2-pyrimidinyl)piperazine (1-PP), an active
      metabolite of both gepirone and ipsapirone. Such findings may explain why prior
      BZ experience impairs the clinical response to buspirone-type anxiolytics acting
      at the 5-HT(1A) receptor.

PMID- 11224089
TI  - Effects of continuous cocaine administration on schedule-controlled behavior in
      rhesus monkeys.
AB  - The behavioral effects of continuous infusion of cocaine for prolonged periods
      were examined in rhesus monkeys responding under fixed-ratio (FR) or fixed
      interval (FI) schedules of food presentation. Operant behavior was examined every
      6h for 30min (FR) or 60min (FI) while saline or increasing doses of cocaine (4.0
      32mg/kg/day) were continuously (24h/day) infused through an intravenous catheter.
      Cocaine initially reduced FR responding and tolerance developed to doses as high
      as 32mg/kg/day over periods of 10 to 35 days. When continuous infusion of cocaine
      (32mg/kg/day) was terminated after 50-80 total days of cocaine exposure, behavior
      was disrupted for several days in three of four monkeys. These behavioral
      disruptions were reversed when cocaine (0.062-0.25mg/kg) was administered i.v.
      10min before sessions in which responding was typically suppressed, suggesting
      that behavioral dependence on cocaine had developed. Continuous infusion of
      cocaine also initially decreased the rate of FI 60s responding and tolerance
      developed to doses of 4.0 and 8.0mg/kg/day. Behavioral disruptions were not
      consistently observed when infusion of cocaine (8.0mg/kg/day) was terminated
      after up to 110 total days of cocaine exposure. Although reinforcement loss was
      comparable under the two schedules of reinforcement, the rate and extent of
      tolerance development varied between the two schedules of reinforcement.
      Therefore, behavioral factors in addition to reinforcement loss contribute to the
      development of cocaine tolerance. In addition, the data suggest that behavioral
      dependence upon cocaine can develop, but only under extreme exposure conditions.

PMID- 11224090
TI  - Effects of 8-OH-DPAT and buspirone in a passive avoidance test and in the
      elevated plus-maze test in rats.
AB  - Benzodiazepines are generally reported to be active in tests based on punished
      responding and in procedures involving exploratory behaviour, but the effects of
      5-HT drugs thus far reported are inconsistent. The effects of the two 5-HT(1A)
      agonists 8-OH-DPAT and buspirone were studied in a passive avoidance test and in
      an elevated plus-maze test. In the passive avoidance test 8-OH-DPAT and
      buspirone, as well as diazepam and chlordiazepoxide, were effective, while, in
      the elevated plus-maze test, the two benzodiazepines were active whereas
      buspirone and 8-OH-DPAT were not. Comparing the effects of the 5-HT(1A) agonists
      with the two benzodiazepines in the passive avoidance test it is suggested that
      this test can be predictive for drugs influencing anxiety. The elevated plus-maze
      test has many advantages, such as the absence of noxious stimuli, compared to
      punishment procedures, but since the 5-HT(1A) agonists do not act as anxiolytic
      compounds in this test, it is suggested that the test does not provide a suitable
      model of anxiety.

PMID- 11224091
TI  - Effects of buspirone on antinociceptive and behaviourial responses to the
      elevated plus-maze in mice.
AB  - Brief exposure to an elevated plus-maze (EPM) induces antinociception in male
      mice, a reaction that is not blocked by opiate receptor manipulations but which
      is completely inhibited by the benzodiazepine receptor agonist, diazepam. The
      present study examined the effects of a non-benzodiazepine anxiolytic, buspirone,
      on EPM antinociception and behaviour. EPM antinociception was completely
      abolished by 10mg/kg buspirone but was largely unaffected by lower doses (0.1
      1.0mg/kg) of the compound. Behaviourally, 1-10mg/kg buspirone produced changes
      indicative of anxiety reduction, although the high dose anxiolytic profile was at
      least partially compromised by a general reduction in behaviour. Data are
      discussed in relation to the proposal that anxiety may be a critical factor in
      non-opioid forms of adaptive pain inhibition.

PMID- 11224092
TI  - Discriminative stimulus properties of (+)- and (-)-n allylnormetazocine: the role
      of training dose in the stimulus substitution patterns produced by PCP/sigma and
      mixed action opioid compounds.
AB  - The discriminative stimulus effects of the stereoisomers of N-allylnormetazocine
      (NANM) were evaluated in separate groups of pigeons trained to discriminate 3.0
      (low) then 7.5 (high) mg/kg (-)-NANM from saline or 3.0 (high) then 1.0 (low)
      mg/kg (+)-NANM from saline. The stimulus effects of the high and low training
      dose of (-)-NANM were shared by the PCP/sigma compounds (+)-NANM, phencyclidine,
      dextrorphan, (+)-cyclazocine and (+)-metazocine but not the putative sigma ligand
      (+)-pentazocine. Doses of naloxone 3-10 times larger than those which antagonize
      the effects of mu and kappa opioids failed to alter these substitution patterns.
      In contrast to the lack of substitution obtained with the mu opioid morphine,
      kappa opioid bremazocine and opioid antagonist naloxone, the mixed action opioids
      (-)-pentazocine, butorphanol, nalbuphine and nalorphine substituted completely
      for the low training dose and partially for the high training dose of (-)-NANM.
      At the low training dose, the substitution patterns produced by these mixed
      action opioids were naloxone-reversible. Complete substitution for both training
      doses of (-)-NANM was also obtained with the mixed action opioids levallorphan
      and (-)-cyclazocine, although these effects were not naloxone-reversible. In
      pigeons trained to discriminate the high and low training dose of (+)-NANM from
      saline, (-)-NANM and the PCP/sigma compounds substituted completely and in a non
      naloxone reversible manner. The relative potencies of these PCP/sigma compounds
      in producing (+)-NANM-like stimulus effects were highly correlated with their
      relative affinity for the sites labeled by PCP but not (+)-NANM. In these
      pigeons, naloxone revealed the (+)-NANM-like stimulus effects produced by (-)
      pentazocine and (-)-cyclazocine, thus suggesting that these mixed action opioids
      have a prominent PCP/sigma-like component. When administered alone or in
      combination with naloxone, the other mixed action opioids evaluated failed to
      substitute for either the high or low training dose of (+)-NANM. The present
      results indicate that the stimulus effects of both training doses of (+)-NANM and
      the high training dose of (-)-NANM are comprised of a PCP/sigma component,
      whereas that of the low training dose of (-)-NANM has both a PCP/sigma and a
      naloxone-reversible, opioid component.

PMID- 11224093
TI  - Hypertonic saline mimics the effects of vasopressin and social recognition in
      rats.
AB  - Injection of hypertonic saline to adult male rats following exposure to a
      juvenile, at a dose known to release peripheral and central vasopressin (10ml/kg
      i.p. of an 0.5M solution), decreased social exploration of the same juvenile when
      it was presented 2h later. This effect of hypertonic saline was blocked by
      pretreatment with subcutaneous injection of 30mg/kg dPTyr (Me) AVP, an antagonist
      of the vasopressor receptors of vasopressin, in intact but not in castrated male
      rats. These results are interpreted in terms of the involvement of androgen
      dependent vasopressinergic neurotransmission in social recognition.

PMID- 11224094
TI  - Modulation of the discriminative-stimulus effects of cocaine by buprenorphine.
AB  - Modulation of the discriminative-stimulus effects of cocaine by the mixed-action
      opioid buprenorsphine was studied in squirrel monkeys trained to discriminate
      cocaine from saline, using a two-lever drug discrimination procedure. Lever
      pressing was maintained under a fixed-ratio 10 schedule of food presentation.
      During test sessions, monkeys received cumulative doses of cocaine after
      presession treatment with either saline or buprenorphine (0.001-0.01mg/kg). After
      pretreatment with saline, cocaine engendered dose-related increases in the
      percentage of cocaine-appropriate responses, reaching a maximum of 99-100 percent
      at doses of 0.3 or 1.0mg/kg. Pretreatment with buprenorphine shifted the cocaine
      dose-response function to the left, resulting in 98-100 percent cocaine
      appropriate responding at doses of cocaine that previously engendered only saline
      appropriate responding. When tested alone, buprenorphine did not occasion cocaine
      appropriate responding at any dose. The results show that although buprenorphine
      does not itself have cocaine-like discriminative-stimulus effects, it can
      potentiate the discriminative-stimulus effects of cocaine.

PMID- 11224095
TI  - Latent inhibition and blocking: further consideration of their construct validity
      as animal models of schizophrenia Commentary on Ellenbroek and Cools "Animal
      models with construct validity for schizophrenia"
AB  - Conventional animal models of schizophrenia do not pretend to account for the
      symptoms of schizophrenia; i.e. they lack construct validity. Ellenbroek and
      Cools (1990) have reviewed a number of other models with construct validity for
      fundamental psychological processes, which are hypothesised to be deficient in
      schizophrenia. Two of these, Latent Inhibition (LI) and the Kamin Blocking effect
      (KB), essentially demonstrate the effects of prior learning on the formation of
      current associations. Animal studies have now shown that LI and KB are disrupted
      by increased dopaminergic activity, and restored by dopaminergic blockade. The
      present paper adds to the database described by Ellenbroek and Cools and
      discusses some further theoretical and practical issues. Specifically: (a)
      Kamin's blocking is disrupted in acute, but not in chronic schizophrenic
      subjects; (b) LI and KB are not simply examples of associative interference; (c)
      The masking task used in adult human studies of LI does not introduce an element
      of blocking as defined by Kamin's paradigm; (d) A direct study of "selective
      attention" in acute schizophrenia suggests that the impairment in LI and KB
      relates to the utilisation of experience about past regularities, rather than a
      generalised attentional deficit; (e) Recent studies, especially with nicotine,
      indicate that LI can be disrupted by drug administration during acquisition only;
      (f) It is now possible to study the release of dopamine, and of other
      transmitters in the nucleus accumbens and in other brain areas, during the
      behavioural paradigm of LI in rats. In this way it should be possible to
      determine directly the neuronal circuitry involved in LI (and KB): this approach
      could explain the link between the neuropathology and neuropharmacology of
      schizophrenia and its symptoms, besides providing more valid test procedures for
      evaluating potential neuroleptic drugs.

PMID- 11224096
TI  - Changes due to food deprivation in the effects of cocaine on the responding of
      pigeons.
AB  - The responding of eight pigeons was maintained under a fixed-ratio 30 schedule of
      food reinforcement. While the pigeons were maintained at 80% of their free
      feeding body weights the effects of presession injection of a range of cocaine
      doses (1.0 or 3.0mg/kg to 10.0 or 17.0mg/kg) were determined. The weights of one
      group of pigeons were then increased to between 90 and 100% of their free-feeding
      weights, while the other group's weights were reduced to 70% of their free
      feeding weights. The effects of cocaine were determined again. Following this,
      pigeons' weights were adjusted to the percentage of free-feeding weight to which
      they had not yet been exposed, and the effects of cocaine determined a third
      time. Cocaine produced dose-dependent decreases in response rates. Decreases were
      observed at smaller cocaine doses when pigeons were relatively food-satiated
      (i.e. 90-100% of free-feeding weight); larger doses were required to decrease
      responding when pigeons were maintained at 70% free-feeding weight. If increased
      resistance to the behaviorally suppressive effects of cocaine when food
      deprivation levels are increased occurs also when cocaine is self-administered,
      this could help account for increases in amounts of cocaine-reinforced behavior
      under conditions of food deprivation.

PMID- 11224097
TI  - Sertindole and several antipsychotic drugs differentially inhibit the
      discriminative stimulus effects of amphetamine, LSD and St 587 in rats.
AB  - The effects of sertindole, clozapine, Cis(Z)-flupentixol and haloperidol on the
      discriminative stimulus properties of d-amphetamine (dopamine DA stimulant), d
      LSD (5-HT(2) agonist) and St 587 (alpha(1)-adrenoceptor agonist; 2-chloro-5
      trifluoromethyl-phenylimino)-imidazolidine) have been studied. Sertindole, a
      putative antipsychotic compound with limbic selectivity, antagonized the effects
      of d-LSD and St 587, whereas that of d-amphetamine was unchanged. Clozapine
      preferentially inhibited St 587, but also antagonized d-LSD and d-amphetamine,
      together with increases in reaction time. Cis(Z)-flupentixol antagonized d
      amphetamine and St 587 effects, whereas haloperidol antagonized d-amphetamine
      only. Behavioural disruption was induced by haloperidol in St 587 and d-LSD
      trained animals. The 5-HT(2) antagonist ketanserin selectively inhibited the
      effect of d-LSD, and the selective alpha(1)-adrenoceptor antagonist prazosin
      partially inhibited the effect of St 587, but did not inhibit d-LSD or d
      amphetamine. The partial inhibition of St 587 effects by prazosin was not further
      increased by co-treatment with haloperidol. Prazosin partially substituted for
      the training dose of St 587. The results indicate that drug discrimination
      techniques can be used to demonstrate different activity profiles of typical and
      atypical neuroleptics. The classical neuroleptics have preferential amphetamine
      antagonistic activity, whereas clozapine has a broad activity profile.
      Furthermore, the atypical neuroleptic sertindole fails to induce acute DA
      antagonism in doses much higher than those inhibiting d-LSD and St 587.

PMID- 11224098
TI  - Subjective and psychomotor effects of nitrous oxide in healthy volunteers.
AB  - The effects of nitrous oxide at subanesthetic doses (0%, 10%, 20%, and 40% in
      oxygen) on mood and psychomotor performance were determined in a group of 12
      healthy volunteers (six males and six females). A randomized, placebo-controlled,
      double-blinded, crossover trial of five experimental sessions was used. Effects
      were measured before, during and after a 30-min inhalation period of the agent,
      using three subjective effects questionnaires (the Profile of Mood States, the
      Addiction Research Center Inventory, and the Visual Analogue Scale); and two
      psychomotor tests (auditory reaction time and Digit Symbol Substitution Test). In
      addition, an End-of-Session questionnaire, administered 60min after cessation of
      inhaling the agent, was used, which measured the subjects' reactions to the agent
      inhaled that day (i.e. peak concentration effect and concentration liking). The
      primary effects observed from nitrous oxide were confined to the inhalation of
      20% and 40% concentrations. Subjects became more confused, sedated, high,
      dysphoric, and stimulated during inhalation of 40% nitrous oxide; fatigue,
      depression and anxiety increased after inhalation of 40% nitrous oxide had
      ceased. Significant or near-significant differences on several measures of
      subjective effects emerged between sexes. On the End-of-Session questionnaire,
      subjects' ratings of the peak effect of nitrous oxide were dose-related. There
      was individual variation in the degree to which subjects liked nitrous oxide:
      eight of the 12 subjects reported liking the 40% concentration, one was neutral,
      and three did not like it. Subjects' performance on the DSST was significantly
      impaired during inhalation of 40% nitrous oxide, but recovered soon after
      inhalation stopped. In summary, nitrous oxide had robust effects on mood, there
      appeared to be sex differences in the magnitude of subjective effects of nitrous
      oxide, and there was some variability in the extent to which subjects liked the
      anesthetic agent.

PMID- 11224099
TI  - Acute opioid administration effects on sensory and motor function in baboons:
      buprenorphine, morphine, and naloxone.
AB  - The effects of acute administration of the opioid compounds buprenorphine,
      morphine, and naloxone were studied on auditory and visual threshold functions
      and reaction time performances in baboons. Baboons were trained in a reaction
      time procedure to hold a lever depressed, and release the lever when a signal was
      presented. Auditory and visual signals were employed in separate sessions. Drug
      was administered 30min prior to testing. Dose-related increases in visual and
      auditory thresholds were observed following buprenorphine, with visual thresholds
      being somewhat more drug-sensitive. Buprenorphine also increased reaction times
      to both high-intensity and low-intensity stimuli. High doses of morphine
      increased reaction times to high-intensity auditory and low-intensity visual
      stimuli; thresholds for both modalities were unaffected by any dose of morphine.
      Naloxone produced no consistent effects on thresholds or reaction times. False
      alarm rates were not significantly changed by buprenorphine, morphine, or
      naloxone.

PMID- 11224100
TI  - Environmental influences on behavioural sensitization to the dopamine agonist
      quinpirole.
AB  - A runway was used to measure locomotor responses to quinpirole (200ug/kg), in
      rats. The locomotor stimulant effect of quinpirole increased progressively over
      successive trials at 3-day intervals. Animals administered quinpirole in the home
      cage were also sensitized, but to a lesser degree than animals tested in the
      runway following quinpirole injections. Exposure to an open field, following
      quinpirole injections, sensitized responsiveness in the runway to an extent
      comparable to that seen following runway exposure. Animals exposed to a movable
      running wheel, following quinpirole injections, were more sensitized to the
      effect of quinpirole in the runway than animals exposed to a locked running
      wheel. The results suggest that the extent of sensitization to quinpirole is
      determined by the behaviour elicited by the drug, rather than the environment in
      which it is administered. An operant conditioning model is proposed to account
      for these effects.

PMID- 11224101
TI  - Effects of the 5-HT3 antagonist ICS 205-930 on benzodiazepine withdrawal signs in
      rats.
AB  - Effects of the 5-HT3 antagonist ICS 205-930 on chlordiazepoxide (CDP) withdrawal
      were assessed in rats treated for 21 days with doses of CDP up to 40mg/kg/day
      (b.i.d.). Withdrawal signs recorded were body weight and 24h food intake, which
      both fell during withdrawal and then recovered. ICS 205-930 (0.001-1.0mg/kg) was
      administered b.i.d. during withdrawal. At no dose over the wide range tested did
      ICS 205-930 reduce withdrawal signs. These data contrast with published findings
      with the 5-HT3 antagonist ondanestron, some of which indicated that ondansetron
      completely alleviated the "anxiogenic" suppression of exploratory behaviour
      observed during benzodiazepine (BZ) withdrawal. Possible reasons for these
      differing findings are discussed. Collectively, these findings suggest that 5-HT3
      antagonists may have limited utility in the clinical treatment of BZ withdrawal.

PMID- 11224102
TI  - Amelioration of some neuroleptic-induced deficits by the NMDA antagonist MK-801
      in a conditioned reaction time task.
AB  - Using a reaction time task sensitive to neuroleptic disruption, we have examined
      the ability of the non-competitive NMDA antagonist MK-801 (0.01-0.16mg/kg) to
      reverse impairments induced by chlorpromazine (2.0mg/kg). Rats were required to
      depress a lever for a randomly determined duration, and release it within 1sec of
      a light cue in order to obtain food reward. Chlorpromazine reduced the overall
      number of lever presses, caused an early cessation of responding, slowed lever
      release in response to an external cue, and increased the time taken to reach the
      food hopper after a correct response. MK-801 differentially influenced these
      impairments, with no dose of drug completely normalising behaviour. The reduction
      in response levels and early termination of responding were partially reversed by
      MK-801, whilst certain doses of the drug completely reversed the increased time
      taken to reach the food hopper. Although MK-801 increased the likelihood that
      chlorpromazine-treated rats would release the lever within the 1sec criterion
      time to obtain reinforcement, reaction times with the drug combination were still
      slower than observed in the control session. Therefore, MK-801 appears to be less
      effective in reversing the chlorpromazine-induced deficit in movement initiation
      than certain other aspects of performance in this task. These findings are less
      promising than those from other studies which have been used to suggest a
      clinical use of NMDA antagonists in the treatment of idiopathic and neuroleptic
      induced parkinsonism.

PMID- 11224103
TI  - Further characterization of adjunctive behavior generated by schedules of cocaine
      self-administration.
AB  - Rhesus monkeys (n = 5), surgically implanted with double-lumen catheters, were
      allowed to self-administer cocaine (0.1 or 0.3mg/kg/injection, i.v.) on one lever
      (COC lever) under several fixed-interval schedules of reinforcement. Responding
      on a second lever (SAL lever) delivered saline (i.v.) under a fixed-ratio 1
      schedule. Responding on both levers was a bitonic function of interval value and
      cocaine dose. A variety of experimental conditions were examined to determine
      whether SAL lever responding could be considered to be adjunctive in nature. SAL
      lever responding did not change when saline injections were discontinued,
      suggesting that SAL lever responding was not maintained by interoceptive stimuli
      associated with the injection. Discontinuation of various exteroceptive stimulus
      changes that had occurred as a consequence of SAL lever responding also did not
      affect the frequency of SAL lever responding. However, when there was no stimulus
      change following a SAL response, response rates on that lever decreased by
      approximately 40-60% indicating that stimulus change played some role in the
      maintenance of the behavior. The introduction of change-over-delays (2-16 s)
      between responding on the SAL and COC levers had little or no effect on
      responding on the SAL lever, suggesting that SAL lever responding was not
      maintained by adventitious reinforcement by cocaine injections. SAL lever
      responding also occurred in these same monkeys when cocaine was available under
      fixed-time or variable-interval schedules of reinforcement. These results confirm
      that presentation of cocaine under interval schedules of reinforcement can
      generate substantial amounts of behavior (pressing the SAL lever) that is not
      necessary for obtaining the drug. Further, the results strongly suggest that the
      behavior can be classified as an adjunctive behavior that is similar to
      adjunctive behaviors generated by the intermittent presentation of other positive
      reinforcers.

PMID- 11224104
TI  - Effects of d-amphetamine and of diazepam on non-punished and punished schedule
      induced drinking in rats.
AB  - Drinking induced in food-deprived rats by a Fixed-Time 1min schedule of food
      presentation was measured by the amount of water consumed per session and the
      number of licks per inter-food interval. Subsequently each lick initiated a 10
      sec signalled delay in the delivery of food, which led to a decrease in drinking
      (punishment). With three rats the effects of d-amphetamine (0.25, 0.5, 1.0,
      2.0mg/kg) were assessed on non-punished and then on punished drinking. With
      another three rats, the effects of diazepam (0.5, 1.0, 2.0, 4.0mg/kg) were
      assessed. The smaller doses of d-amphetamine had no consistent effect on overall
      measures of non-punished schedule-induced drinking, but the largest dose
      decreased them. With the signalled delay d-amphetamine increased punished
      schedule-induced drinking. Non-punished drinking was increased by small doses of
      diazepam and decreased by the largest dose, but no dose of diazepam affected
      punished drinking.

PMID- 11224105
TI  - Social competition in dominant rats can be attenuated by anxiogenic drugs.
AB  - In a previous study it was found that, in groups of three male Wistar rats
      competing for access to sweetened milk, access to the milk by subordinate animals
      was increased after administration of anxiolytic drugs. This result was
      consistent with the hypothesis that levels of social competition were associated
      with different levels of fear. The present study involved the administration of
      anxiogenic drugs to rats found to be dominant during similar social competition
      tests. Dose-related decreases in access to the milk during competition sessions
      were produced by FG 7142 (0.3-5.0mg/kg), pentylenetetrazole (0.6-10mg/kg) and
      yohimbine (1.0-4.0mg/kg). These three compounds were also investigated on the
      milk intake of the same animals tested singly. It was found that there was a wide
      separation between doses active in the two conditions with FG 7142 and
      pentylenetetrazole, but a much less wide separation with yohimbine. These results
      are further evidence that tests of social competition provide sensitive
      behavioural baselines for assessing the effects of drugs which modulate anxiety
      levels.

PMID- 11224106
TI  - Control of cigarette smoking topography: smoke filtration and draw resistance.
AB  - Systematic changes occur in the topography of puff and inhalation behavious as a
      cigarette is smoked. The role of various physical properties of the cigarette in
      controlling puff and inhalation behaviors was investigated in two experiments.
      The first experiment manipulated presmoking cigarette length while the second
      manipulated smoke filtration and cigarette draw resistance in an independent
      fashion. The characteristic progressive decrease in puff volume observed with
      each succeeding puff of a cigarette was not due to smoke satiation, fatigue, or
      visual cues. Although draw resistance can be a major determinant of puff volume,
      it did not appear to be a central mechanism accounting for the progressive
      decrease within normally smoked cigarettes. Rather, this decrease in puff volume
      appeared to be a response to the increasingly less filtered, more concentrated
      smoke. Although inhalation and exhalation volumes appeared weakly responsive to
      smoke satiation and/or fatigue, the subjective qualities of smoke "taste" and
      "satisfaction" also appeared to control these respiratory parameters. The present
      study provides some evidence suggesting that inhalation parameters may play a
      role in determining smoke exposure.

PMID- 11224107
TI  - Stimulus generalization from cocaine to analogs with high in vitro affinity for
      dopamine uptake sites.
AB  - Previous research has shown that phenyltropane derivatives of cocaine are very
      potent ligands for dopamine transporters in in vitro binding and uptake, and in
      in vivo binding assays. In the present study, these analogs were tested for their
      ability to substitute for cocaine in rats trained to discriminate cocaine from
      saline. Results indicate that these compounds are from 6-13 times more potent
      than cocaine in producing cocaine-appropriate responding. This provides further
      evidence in support of the importance of dopamine uptake inhibition for the
      behavioral effects of cocaine, and suggests utility of these compounds in
      understanding cocaine abuse.

PMID- 11224108
TI  - Opioid nature of learned helplessness and stress induced analgesia observed
      without re-exposure to shock.
AB  - It has been shown that uncontrollable shocks that produce learned helplessness
      also produce long-term opioid analgesia if th animal is re-exposed to shock
      immediately before the test. The present study was conducted in order to
      investigate if this effect can be observed 24h after the uncontrollable shock
      treatment without re-exposure to shock, and if it is opioid mediated. Long-term
      analgesia was found in the absence of re-exposure to shock, and was prevented by
      an i.p. injection of naloxone (10mg/kg) administered 10min before the test. The
      learned helplessness effect produced by the same shock treatment was prevented by
      the administration of 10 and 20mg/kg of naloxone 10min before the shuttlebox
      test, but not by a lower naloxone dose (5mg/kg). These findings suggest that the
      shock re-exposure requirement proposed in previous studies is not crucial in
      determining the long-term analgesia, and that both the long-term analgesia and
      the learned helplessness effect produced by this shock treatment were opioid
      mediated.

PMID- 11224109
TI  - Resistance of baseline activity in the elevated plus-maze to exogenous
      influences.
AB  - Factors which may influence the exploratory behaviour of male Sprague-Dawley rats
      in the elevated plus-maze were investigated in two series of experiments. The
      first dealt with factors related to the test apparatus: light level, spatial
      configuration and height of the maze. The second dealt with factors intended to
      modify the internal state of the animals by an acute stressful treatment: partial
      immersion in water, forced immobilization for 10 or 20min, electric shock or
      20min preexposure to open or closed arms. Chlordiazepoxide, 5mg/kg i.p., was
      administered as the reference drug and significantly increased the exploration of
      the open arms in all but one of the experiments. In saline-treated animals, no
      effects of the environmental or behavioural treatments were detected. This
      resistance to exogenous manipulations suggests that "plus-maze-anxiety" should be
      considered as a situational-bound response, i.e. characteristic of rodents placed
      in this particular situation.

PMID- 11224110
TI  - Prolonged social recognition in male rats treated with alaptide or oxiracetam.
AB  - Male rats form short-term memory for the olfactory characteristics of juvenile
      conspecifics. Alaptide, a synthetic derivative of the hypothalamic MIF, given
      subcutaneously at doses of 0.5 and 1.0mg/kg immediately after the initial
      exposure to an adult male, reduced the time spent by adults in social
      investigation of the same juvenile upon re-exposure 4h, 24h and 72h after the
      initial exposure. Oxiracetam (30 and 60mg/kg) had a similar effect. Both drugs
      were ineffective in animals re-exposed to a novel juvenile. Thus, both alaptide
      and oxiracetam improved an animal's capacity to recognize the juvenile. The
      findings may be interpreted in terms of a prolonged retention of memory traces
      based on olfactory information received during a short social interaction.

PMID- 11224111
TI  - Naloxone benzylhydrazone is a u-selective opioid antagonist without kappa agonist
      effects in rhesus monkeys.
AB  - Naloxone benzoylhydrazone (NalBzoH) has been suggested to be a selective opioid
      agonist, exerting its effects through the kappa(3) subtype of opioid receptor. In
      the present experiments NalBzoH was studied for its discriminative stimulus,
      analgesic, and respiratory effects in rhesus monkeys. Up to the largest doses
      administered (1.0-3.2mg/kg), NalBzoH failed to substitute for the discriminative
      stimulus effects of the kappa agonist ethylketocyclazocine or those of the u
      agonist alfentanil. However, in morphine-treated (3.2mg/kg/day) monkeys NalBzoH
      substituted completely for the discriminative stimulus effects of the opioid
      antagonist naltrexone. NalBzoH antagonized the discriminative stimulus effects of
      alfentanil in morphine-treated subjects and, at larger doses, antagonized the
      discriminative stimulus effects of ethylketocyclazocine. NalBzoH did not produce
      analgesic effects and had only modest effects on respiration. However, NalBzoH
      antagonized the analgesic effects as well as the respiratory-depressant effects
      of alfentanil; at doses 10-15 times larger than those that antagonized
      alfentanil, NalBzoH also antagonized analgesic effects of the kappa agonist U
      50,488. For both u and kappa agonists, NalBzoH was slightly more potent in
      antagonizing discriminative stimulus effects as compared to analgesic effects.
      Thus, NalBzoH is a u-selective opioid antagonist in rhesus monkeys and is
      equipotent to naloxone in antagonizing alfentanil. While demonstrating u
      selective antagonism, the current study fails to provide support for the proposed
      kappa agonist actions of NalBzoH.

PMID- 11224112
TI  - Effects of phencyclidine-like drugs on responding under multiple fixed ratio,
      fixed interval schedules.
AB  - The effects of phencyclidine and a series of related drugs were studied on rates
      and patterns of responding by rats under a multiple fixed-interval 300s, fixed
      ratio 30-response schedule of food presentation. Dizocilipine produced large
      increases in the rate of FI responding and smaller increases in the rate of FR
      responding. TCP slightly increased the rate of FI responding and PCE slightly
      increased the rate of FR responding. Higher doses of all drugs decreased rates of
      responding under both schedule components with the potency order of dizocilpine >
      PCE > PCP > TCP > ketamine. This relative potency for decreasing rates of FI and
      FR responding correlated highly with the affinity of these drugs for PCP
      receptors, suggesting that the rate decreasing effects of these drugs are
      mediated through these receptors. An analysis of local rates of responding within
      the FI suggested that dizocilpine was different from the arylcyclohexylamines in
      that it was the only drug that increased rates of responding late in the FI
      component. Previous reports have shown that the ability of arylcyclohexylamines
      to increase punished responding and to act as discriminative stimuli are
      correlated highly with binding to PCP receptors. The present experiments suggest
      that decreases in rates of responding under multiple schedule control are also
      mediated by PCP receptors.

PMID- 11224113
TI  - Ritanserin overcomes exploratory inhibition induced by cocaine withdrawal.
AB  - Rats given a subchronic cocaine treatment for 10 days display an inhibition of
      exploratory behaviour 24h after the last cocaine treatment in the open field
      test. As compared to the vehicle controls, the exploratory inhibition could be
      measured in terms of a longer latency to enter the open area, a reduction in the
      time spent in the open field and a decrease in the number of transits from the
      small dark compartment into the open area. The serotonin (5-HT(2/1C)) antagonist
      ritanserin, given subcutaneously 1h prior to testing, overcame this behavioural
      inhibition. At doses between 0.04mg/kg and 10.0mg/kg ritanserin, a complete
      normalization of exploratory activity was obtained. In chronic vehicle treated
      rats, ritanserin did not increase exploration. Therefore the effects of
      ritanserin cannot be attributed to a general activation. The results are
      discussed with regard to withdrawal anxiety and a possible therapeutic role of
      ritanserin in drug addicts.

PMID- 11224115
TI  - A bibliography of drug discrimination research, 1989-1991.

PMID- 11224114
TI  - The effects of amphetamine, apomorphine, SKF 38393, quinpirole and bromocriptine
      on responding for conditioned reward in rats.
AB  - The present study investigated the effects of the dopamine (DA) D1 selective
      agonist, SKF 38393, and the D2 selective agonists, quinpirole and bromocriptine,
      on responding for conditioned reward. The nonselective DA agonist apomorphine and
      the indirect agonist amphetamine, were also evaluated. Male rats (n = 302) were
      tested in a procedure consisting of three distinct phases. During the pre
      exposure phase the rats were exposed to an operant chamber containing two levers;
      one lever produced a lights-off stimulus (3s) and the other a tone stimulus (3s).
      This was followed by 4 conditioning sessions during which the levers were removed
      and rats received pairings of the lights-off stimulus (80 per day) and food,
      presented according to a variable time 45s schedule. Two test sessions followed
      during which the levers were present and the number of responses made on each
      lever was calculated as a ratio of the number of responses made during pre
      exposure. Drugs were administered prior to each test session. A saline group
      showed a higher ratio of responding for the lights-off stimulus than the tone
      stimulus, indicating that the lights-off stimulus had become a conditioned
      reward. Amphetamine (0.01-2.0mg/kg) and to a lesser extent, quinpirole (0.01
      5.0mg/kg) and bromocriptine (0.05-10.0mg/kg) dose-dependently increased
      responding and specifically enhanced responding on the lever producing the
      conditioned reward. Apomorphine (0.1-5.0mg/kg) increased responding on both
      levers at higher doses but the conditioned reward effect was lost. SKF 38393 (0.1
      10.0mg/kg) appeared to impair the acquisition of responding for conditioned
      reward. The results were interpreted as indicating that responding for
      conditioned reward may be dependent on a D1 receptor-mediated reward signal.

PMID- 11224116
TI  - Tolerance to the reinforcing effects of cocaine.
AB  - This study tested the hypothesis that prolonged exposure to high doses of cocaine
      would produce tolerance to the reinforcing effects of cocaine. We determined the
      rate of administration of low doses of cocaine in rats and then exposed these
      subjects to high doses of cocaine (5mg) three-times a day for 1 week. This
      treatment caused a 2-fold faster intake of cocaine, and the lowest dose of
      cocaine that would maintain self-administration was double the previous threshold
      dose. To our knowledge this is the first controlled demonstration of tolerance to
      the reinforcing effects of cocaine produced by chronic exposure to the drug, and
      we suggest that this tolerance may be a key marker for the development of drug
      dependence.

PMID- 11224117
TI  - Selective tolerance to discriminative stimulus effects of morphine or d
      amphetamine.
AB  - Pharmacological selectivity of tolerance to the discriminative stimulus effects
      of morphine or d amphetamine was examined in pigeons trained to discriminate
      among 3.2mg/kg morphine, saline, and 1.8mg/kg d-amphetamine under a 3-key fixed
      ratio 30 schedule of food delivery. Cumulative doses of morphine (0.32-10mg/kg)
      or d-amphetamine (0.10-3.2mg/kg) evoked morphine-or d-amphetamine-key responding,
      respectively, in a dose-dependent manner. Suspending training and administering
      repeated doses of morphine (32mg/kg b.i.d.) for 1 week increased the dose of
      morphine required for morphine-key responding approximately 5-fold, without
      altering sensitivity to d-amphetamine. Conversely, repeated treatment with d
      amphetamine (5.6mg/kg b.i.d.) increased the dose of d-amphetamine required for d
      amphetamine-key responding approximately 7-fold, without decreasing sensitivity
      to morphine. Repeated treatment with saline (1ml/kg b.i.d.) for 1 or 2 weeks did
      not alter sensitivity to stimulus effects of either morphine or d-amphetamine.
      Sensitivity to stimulus effects of morphine recovered fully within 1 week after
      morphine treatment ended; sensitivity to stimulus effects of d-amphetamine
      recovered partially within 3 days after d-amphetamine treatment ended. For
      morphine, but not for d-amphetamine, increases in the dose required for stimulus
      effects were accompanied by increases in the dose required for rate-reducing
      effects. These results demonstrate that tolerance to discriminative stimulus
      effects of morphine and d-amphetamine is pharmacologically selective and suggest
      that pharmacotherapies targeted to one drug of abuse may produce little change in
      sensitivity to subjective effects of drugs from a different pharmacological
      class.

PMID- 11224118
TI  - Effect of dose on the ability of caffeine to serve as a reinforcer in humans.
AB  - This study tested the effects of dose on the reinforcing effects of caffeine in
      humans. Eight moderate coffee drinkers were given concurrent access to
      decaffeinated coffee vs. decaffeinated coffee to which different doses of
      caffeine (25, 50, 150 and 200mg/cup) were added. Subjects were tested across
      several independent double-blind trials. The coffees with 25mg of caffeine were
      repeatedly self-administered at a rate greater than that of decaffeinated coffee
      in two of six subjects, the 50mg dose in four of eight subjects, the 150mg dose
      in three of six subjects, and the 200mg dose in none of the three subjects
      tested. Headaches, drowsiness and fatigue occurred with use of decaffeinated
      coffee in five subjects. When these symptoms occurred, there was a greater
      probability of self-administration of the caffeinated coffee. We conclude that
      doses of caffeine similar to those in tea or soda can serve as reinforcers.

PMID- 11224119
TI  - Factors influencing the subjective response to caffeine.
AB  - The subjective effects of caffeine, the most widely used psychoactive drug, vary
      widely from person to person. The factors responsible for these individual
      differences remain largely unknown. Data from 36 healthy adults who were light to
      moderate users of caffeine were examined with the goals of characterizing the
      subjective effects of caffeine and identifying factors which might correlate with
      or predict these effects. Subjective effects of 100 and 300mg caffeine were
      measured with standardized questionnaires. The low dose of caffeine was found to
      produce negligible subjective effects in the group as a whole, while the high
      dose produced mild stimulant and anxiogenic effects. As expected, there was
      considerable intersubject variability in the subjective effects of caffeine.
      There was no correlation between stimulant and anxiogenic effects after the high
      dose. Light caffeine users were more accurate than heavy caffeine users in
      identifying the high dose of caffeine as an active drug, but there was no
      evidence that light users were generally more sensitive to the subjective effects
      of caffeine. Current alcohol use, prior recreational use of stimulants, and
      baseline level of self-reported arousal appeared to influence subjective response
      to caffeine. Other variables (personality, gender, baseline anxiety, and prior
      use of other drugs) showed no relationship with mood response to caffeine.

PMID- 11224120
TI  - Discriminative stimulus effects of alprazolam and diazepam: generalization to
      benzodiazepines, antidepressants and buspirone.
AB  - Rats in one group were trained to discriminate alprazolam (1.0mg/kg, i.p.) and in
      another group diazepam (3.0mg/kg, i.p.) from saline in a two-lever drug
      discrimination procedure. Food presentation occurred after 10 consecutive
      responses on the lever associated either with the training drug or with saline.
      Alprazolam, diazepam, lorazepam and chlor diazepoxide increased responding on the
      drug-associated lever in a comparable dose-related manner in both groups of rats:
      the relative order of potency was lorazepam >/= alprazolam > diazepam >/=
      chlordiazepoxide. Flumazenil (10.0mg/kg, i.p.) attenuated the effects of the
      training drugs. A range of doses of buspirone and four drugs having
      antidepressant properties (amitriptyline, fluoxetine, cericlamine, imipramine)
      then were studied in both groups of rats. All five drugs caused approximately 40%
      increases (group mean) in drug-appropriate responding in alprazolam-trained rats
      whereas only amitriptyline partially substituted for diazepam. The results
      indicate that alprazolam has interoceptive stimulus effects that overlap with the
      stimulus effects of diazepam, yet the effects of alprazolam may not be identical
      to those of diazepam because the antidepressant drugs and buspirone substituted
      partially for alprazolam but generally not for diazepam.

PMID- 11224121
TI  - Chronic treatment with clomipramine and mianserin increases the hierarchical
      position of subdominant rats housed in triads.
AB  - Male Wistar rats housed in triads under a 12h: 12h light-dark schedule exhibit
      intense levels of social behaviour, involving all group members equally, at the
      onset of every dark phase. Analysis of this social behaviour yields the group's
      hierarchical structure (based on the proportion of wins attained during social
      interaction) consisting of a dominant, subdominant and subordinate rat. Chronic
      treatment of the subdominant rats with the antidepressant drugs clomipramine,
      10umol/kg day, and mianserin, 0.33umol/kg/day, via subcutaneously-implanted
      osmotic mini-pumps, increased the proportion of wins attained during encounters
      with their sham-operated cage partners by day 6 of treatment. This increase was
      maintained throughout the remaining period of treatment and was generally at the
      expense of the level of dominance of the dominant rat. It is argued that the
      ability of clomipramine and mianserin to increase the proportion of wins attained
      by subdominant rats parallels the previously-reported drug-induced release of
      social and agonistic behaviour which is thought to be indicative of
      antidepressant activity.

PMID- 11224122
TI  - Second-order (environmental) conditioning of a taste aversion in rats.
AB  - Four groups of rats (n = 10/group) were conditioned in a taste aversion task
      using a second-order reinforcer associated with precipitated morphine withdrawal.
      Rats in CS+, CS- and CS(random) groups were exposed to a chronic morphine
      (morphine sulfate, MS) dosing regimen. A control group received equivalent
      volumes of saline. All rats then received daily i.p. injections of naloxone HCI
      (1.0-3.2mg/kg), inducing precipitated morphine withdrawal in group-dependent
      unique environments. The 4-h withdrawal trials were terminated by a 20mg/kg MS
      injection (MS treatment groups only) and returned to their home cage. After a 1
      week wash-out was imposed, all subjects were exposed to a conditioned taste
      aversion (CTA) task using environmental stimuli (CSI) from Phase 1 paired with
      saccharin (CS2) in a second-order conditioning procedure. The CS+ group developed
      a significant CTA; the CS- and CS(random) groups increased their consumption of
      saccharin. The saline group was unaffected by the treatment conditions. The data
      demonstrate the salience and importance of environmental stimuli and suggest a
      role for such conditioning in drug relapse phenomena.

PMID- 11224123
TI  - A characterization of nicotine-induced tolerance: evidence of pharmacological
      tolerance in the rat.
AB  - The present studies were conducted in order to confirm and extend previous
      findings that the mechanisms of tolerance to the behaviorally disruptive effects
      of nicotine in a operant model were primarily pharmacological. Both the
      traditional methodology employing the determination of dose response curves
      before and after chronic drug administration and a methodology which omits the
      generation of dose response curves were utilized in these investigations of
      nicotine-induced tolerance. Rats developed tolerance to both pre- and post
      session administration of nicotine, suggesting that the mechanisms of tolerance
      to the disruptive effects of nicotine are primarily pharmacological. The
      mechanisms underlying these effects, however, remain to be evaluated.

PMID- 11224124
TI  - Role of amygdaloid nuclei in the anxiolytic effects of benzodiazepines in rats.
AB  - Previous work has implicated the amygdala, especially the central and basolateral
      nuclei, in the anxiolytic effects of benzodiazepines in animal models of anxiety.
      However there are contradictory findings on the relative importance of each
      nucleus. The experiments reported here show that midazolam (1.0ug) injected
      bilaterally into the basolateral nucleus significantly increased open arm
      activity on the elevated plus-maze. In contrast midazolam (1.0ug) had no effect
      when injected into the central nucleus. These results suggest that the
      basolateral nucleus is one substrate mediating anxiolytic effects. However, a
      brief review of the literature supports the suggestion that both nuclei can be
      involved, but findings will depend upon the particular paradigm used.

PMID- 11224125
TI  - Memantine has phencyclidine-like but not cocaine-like discriminative stimulus
      effects in rats.
AB  - It has recently been reported that the amantadine derivative, memantine, which is
      used in the treatment of Parkinsonism, has N-methyl-D-aspartate (NMDA) antagonist
      properties. In order to investigate whether the behavioural effects of memantine
      could also be mediated through this mechanism the drug was administered to rats
      trained to discriminate phencyclidine (3mg/kg) from saline. Memantine produced a
      dose-related (2.5-10mg/kg) substitution for phencyclidine. Neither amantadine nor
      cocaine substituted for phencyclidine. In rats trained to discriminate cocaine
      (10mg/kg) memantine did not substitute. These results show that memantine has
      phencyclidine-like but not cocaine-like discriminative stimulus effects
      indicating that the behavioural actions of memantine, like those of
      phencyclidine, are probably produced by a non-competitive inhibition of NMDA
      receptors.

PMID- 11224126
TI  - Potentiation of behavioural effects of a calcium channel antagonist, nifedipine,
      by ipsapirone.
AB  - The synergistic effect between the 5-HT(1A) agonist ipsapirone and the calcium
      channel antagonist, nifedipine, was studied in animal models of anxiety and
      depression. Ipsapirone (1.5, 3.0 and 6.0mg/kg) dose dependently potentiated the
      behavioural effects of a small and ineffective dose of nifedipine (2.0mg/kg) in
      the two experimental paradigms. This potentiation was revealed by a decrease in
      immobilisation time in the forced swim test (antidepressant-like effect) and by
      an increase in water-consumption in a novel environment (anxiolytic-like effect).
      The data obtained are discussed in terms of the neurochemical effects of
      ipsapirone on the serotonergic system, and the possible interaction between
      nifedipine and this system.

PMID- 11224127
TI  - Sensitization of haloperidol-induced hypophagia is contingent on behavioral
      experience with food.
AB  - Groups of rats were given injections of haloperiodol (0.31mg/kg) at weekly
      intervals either before or after access to sweetened milk. Control groups were
      given injections of saline. At the end of the chronic regimen, all groups
      received a single injection of haloperidol (0.15mg/kg) prior to milk access. Rats
      injected with the drug before milk during the chronic phase showed a progressive
      decrease in milk intake. When subsequently challenged with a lower dose, this
      group ingested less milk than any of the other groups, which did not differ from
      one other. These results demonstrate that sensitization of haloperidol-induced
      hypophagia is contingent on experience with milk while in the drugged state.

PMID- 11224128
TI  - Pharmacological approaches to learning and memory.

PMID- 11224129
TI  - Pharmacological mechanisms and animal models of cognition.
AB  - Requirements for an effective animal model of cognition are discussed with
      special reference to the cholinergic hypothesis of Alzheimer's disease. It is
      argued, with reference to research on vasopressin and ACE inhibitors, that many
      putative animal models of cognition lack predictive clinical validity because
      they either confound the effects of cognitive and arousal processes, or fail to
      model a specific component of cognitive functioning. A survey of recent research
      on the cholinergic hypothesis illustrates how these weaknesses can be overcome.
      Studies involving scopolamine and basal forebrain excitatory amino acid lesion
      models of the cholinergic deficit in Alzheimer's disease have employed a delayed
      matching-to-position test in rodents which, unlike passive avoidance, allows the
      effects of memory and attentional variables to be distinguished. In combination
      with recent human studies, these experiments suggest that the cholinergic system
      has a major role in executive control of attentional resources, and lead to the
      recommendation of a 'top down' strategy in the investigation of neurochemical
      processes and pharmacological mechanisms underlying cognition.

PMID- 11224130
TI  - Cholinergic replacement strategies in Alzheimer's disease: the postsynaptic
      dilemma. Commentary on Dawson et al. "Pharmacological mechanisms and animal
      models of cognition"

PMID- 11224131
TI  - Are better, more selective tests of cognitive performance by animals really
      necessary for the development of effective treatments for Alzheimer's disease?
      Commentary on Dawson et al. "Pharmacological mechanisms and animal models of
      cognition"

PMID- 11224133
TI  - From mice to men and vice versa: comparative cognition and behavioural
      pharmacology. Commentary on Olton et al. "Comparative cognition and assessment of
      cognitive processes in animals"

PMID- 11224132
TI  - Comparative cognition and assessment of cognitive processes in animals.
AB  - Comparative cognition is an approach that seeks to describe cognitive processes
      in general computational terms so that the appropriate behavioral testing
      procedures can be established for any animal, including humans. Some examples of
      this approach are discussed in the context of memory and attention, emphasizing
      the ways in which historically disparate research traditions can be integrated
      together to provide new approaches for behavioral testing in animals. This
      comparative approach helps to integrate animal models using different species,
      and to develop tasks that have more direct connection to the assessment of
      cognitive processes in people.

PMID- 11224134
TI  - Comparing cognition: an important enterprise? Commentary on Olton et al.
      "Comparative cognition and assessment of cognitive processes in animals"

PMID- 11224135
TI  - Cholinergic function in the aged brain: implications for treatment of memory
      impairments associated with aging.
AB  - The cholinergic hypothesis of impaired memory in Alzheimer's disease has
      stimulated interest in cholinergic function of the brain in relation to the more
      common and less serious impairments of memory associated with normal (non
      disease) aging. Unlike Alzheimer's disease, it is not clear whether normal aging
      results in a loss of cholinergic innervation to cerebral cortex and hippocampus,
      but prevailing evidence suggests that certain aspects of brain cholinergic
      function are diminished with advancing age. Human and animal data on the effects
      of aging on cholinergic systems of the brain are reviewed and are discussed in
      connection with the role these effects may play in the etiology and treatment of
      the learning and memory impairments associated with aging.

PMID- 11224136
TI  - Within-subject behavioral analysis of recent memory in aging mice.
AB  - Two experiments addressed the utility of a T-maze, delayed reversal paradigm for
      assessment of recent memory impairment in aging C57BL/6NNia mice. This paradigm
      involved acquisition of a learning set for identification of the correct arm
      choice in a daily multiple-trial discriminated avoidance session. During each
      session, the correct arm was always opposite that entered on an initial
      "information trial" and maximal performance thus required a reversal (or "lose
      shift") strategy. Once the learning set had been acquired, retention performance
      was examined following delays of varying length which were introduced following
      the information trial during each session. In the first experiment, acquisition
      and retention components of delayed reversal were considered in a cross-sectional
      study involving separate groups of mice aged 7, 10, 15, or 27 months. Analysis of
      acquisition components suggested that relative to young mice, the old mice were
      slower to acquire both the first reversal and the learning set. Analysis of the
      retention phase suggested that memory decay gradients for goal arm discrimination
      became more pronounced with increasing age, whereas decay gradients for the
      avoidance response were similar among the age groups. Correlational analysis of
      data for the old mice suggested independence of age-related deficits in the
      acquisition and recent memory components of the delayed reversal paradigm. In the
      second experiment, survivors from the previous 7- and 10-month-old groups were
      retested when 27 months of age. The cross-sectional and longitudinal data led to
      the same conclusions with regard to the effect of age on recent memory function.
      Overall, these results suggest that the delayed reversal paradigm will be a
      valuable tool in the analysis and evaluation of interventions potentially
      affecting age-related cognitive impairment.

PMID- 11224137
TI  - Neurohypophyseal hormone receptors in the septum are implicated in social
      recognition in the rat.
AB  - The effects on social recognition memory of (Arg(8))-vasopressin (AVP-(1-9),
      [pGlu(4), Cyt(6)]AVP-(4-8) and oxytocin locally administered into the rat's
      septum were investigated. In the behavioural paradigm used, a juvenile intruder
      was presented to an adult resident male rat twice for 5 min, with an inter
      exposure interval of 120 min. Peptide-free residents investigated the juvenile
      during the second encounter as long as during the first encounter. Intraseptal
      injection just after the first encounter with graded doses of (Arg(8))
      vasopressin, [pGlu(4),Cyt(6)]AVP-(4-8) or oxytocin caused a decrease of social
      investigation, as compared to placebo treatment, indicating facilitation of
      social recognition. The least effective dose was 100pg, 200pg and 300pg
      respectively. The action of vasopressin was blocked by both
      d(CH(2))(5)[Tyr(Me)(2)]AVP and d(CH(2))(5)[D-Ile(2)Ile(4)]AVP, V(1) and V(2)
      vasopressinergic receptor antagonists, but not by desGly(NH(2))(9)
      d(CH(2))(5)[Tyr(Me)(2)Thr(4)]-OVT, an oxytocinergic receptor antagonist. None of
      the antagonists blocked the oxytocin-facilitating action on social recognition.
      They also did not affect social recognition when injected alone. The effects of
      vasopressin seem to be mediated by vasopressinergic receptors dissimilar to those
      found in the periphery, while the receptors involved in the action of oxytocin
      remain to be elucidated.

PMID- 11224138
TI  - Comparison of radial maze performance of rats after ibotenate and quisqualate
      lesions of the forebrain cholinergic projection system: effects of
      pharmacological challenge and changes in training regime.
AB  - Rats with ibotenic or quisqualic acid lesions to cholinergic projections showed
      similar significant increases in both short-term working and long-term reference
      memory errors in radial maze spatial (place) and nonspatial (cue) tasks,
      throughout a period of 10 weeks after lesioning. All types of error were dose
      relatedly reduced to a similar extent in lesioned rats after treatment with
      nicotine and the beta-carboline ZK93426. Performance of controls was not affected
      by nicotine, but errors were increased with the higher doses of ZK93426. In
      contrast, amphetamine increased errors in both control and lesioned rats. With
      extensive training, lesioned rats improved to control level, but were more
      disrupted than controls by a break in testing, which reinstated high error rates
      to an equivalent extent in lesioned groups. Choline acetyltransferase (ChAT)
      activity showed a comparable degree of depletion in quisqualate and ibotenate
      lesioned groups to around 60% of control level in cortex and 75% in hippocampus.
      These results indicate that at volumes and concentrations that produced an
      equivalent degree of ChAT depletion, detrimental effects of ibotenate and
      quisqualate lesions on radial maze performance were very similar. The time course
      of improvement with over-training and impairment after a break in training were
      also comparable with both lesioning agents. Reduced errors following compounds
      acting directly (nicotine) or possibly indirectly (ZK 93426) to enhance
      cholinergic function, but not after amphetamine, suggested that damage to
      cholinergic neurons contributed to the behavioural deficits induced by both
      ibotenic and quisqualic acid.

PMID- 11224139
TI  - Patterns of facilitation of memory by nicotine.
AB  - A single oral dose of 1.5mg of nicotine was administered to healthy young normal
      males in a placebo-controlled double-blind study. The nicotine produced a
      significant improvement in the number of words recalled from a 32 item list. An
      examination of the individual serial position curves showed that most subjects
      were recalling either predominantly from the first half of the list or
      predominantly from the second half of the list. Examination of these groups
      separately showed that nicotine improved recall for the part of the list that was
      being recalled better in the placebo condition. These results are consistent with
      the hypothesis that nicotine was supplying additional processing resources and
      that deployment of these is under the strategic control of the subject.

PMID- 11224140
TI  - Impairment of working memory by neuronal degeneration with NMDA in rat
      hippocampal CA-1.
AB  - Rats were trained on a three-panel runway task prior to injections of N-methyl-D
      aspartate (NMDA; 40nmoles/ul/side) into the dorsal hippocampus. One week after
      the treatment, animals did not show any change in the number of errors on the
      first runway trial (reference memory), with one correct white and two incorrect
      black panels at each choice point, whereas they showed a marked increase in the
      number of errors on the following (2nd-6th) trials (working memory) with all
      black panels. The memory deficit persisted at least for 10 days. After the
      experiments, histological studies showed neuronal degeneration of hippocampal CA
      1 pyramidal cells in all NMDA-treated rats but not in vehicle-treated rats.
      Pretreatment with the NMDA receptor antagonist MK-801 (3 or 10mg/kg, i.p) before
      the NMDA injections protected both the neuronal degeneration and the memory
      deficit. These findings suggest that selective neuronal degeneration induced by
      excessive stimulation of NMDA receptors in hippocampal CA-1 impaired working
      memory, but not reference memory.

PMID- 11224141
TI  - NMDA-receptor-dependent, muscimol-sensitive role of the entorhinal cortex in post
      training memory processing.
AB  - The bilateral infusion into the entorhinal cortex of the NMDA receptor
      antagonist, AP5 (5.0ug) or of the GABA(A) agonist, muscimol (0.03ug) 90min after
      training but not 30min before training, 0min after training or 10min before
      testing, hindered retention test performance 24h after inhibitory avoidance in
      rats. Glutamate (5.0ug) or picrotoxin (0.08ug) infused 90min after training had
      no effect. In animals trained with a low level footshock a second training
      session, 120min after the first, was needed in order to obtain a good retention
      test performance. This was taken to reflect summation of the consecutive memory
      traces left by the two training sessions. In these animals, the infusion of AP5
      or muscimol into the entorhinal cortex between the two training sessions impeded
      their summation. The present results suggest that the entorhinal cortex plays a
      late role in memory processing, that this role does not need a hyperactivation of
      the entorhinal cortex, and that it is important for the interaction between
      consecutive memory traces.

PMID- 11224142
TI  - Effects of strychnine-insensitive glycine receptor antagonists and sigma agents
      on working memory performance: comparison with dizocilpine and scopolamine.
AB  - The strychnine insensitive glycine receptor antagonists (+/-) HA 966 (2.5, 3.5,
      4.25 and 5.0mg/kg) and 7 chlorokynurenic acid (5.0, 10.0, and 15.0mg/kg), the
      putative sigma agents NPC 16377 (5.0 and 8.0mg/kg), BMY 14802 (5.0, 7.5 and
      10.0mg/kg), and ifenprodil (5.0 and 7.0mg/kg) and the reference agents
      scopolamine and dizocilpine [(+) MK 801] were evaluated in a nonspatial delayed
      matching to sample working memory task in rats. (+/-) HA 966 impaired accuracy at
      the longest retention interval and decreased response probability measures. 7
      Chlorokynurenic acid was essentially without effect. The noncompetitive NMDA
      antagonist dizocilpine reduced accuracy at all retention intervals, decreased the
      probability of a choice response and increased the probability of an intertrial
      interval response. The anticholinergic agent scopolamine selectively reduced
      accuracy at the longest retention interval but did not affect other performance
      measures. Sigma agents decreased response probability measures but did not affect
      accuracy at any retention interval. The results support the notion that sigma
      agents, glycine antagonists and NMDA antagonists produce different effects in
      cognitive tasks including working memory performance.

PMID- 11224143
TI  - Differential effects of MK-801, NMDA and scopolamine on rats learning a four
      member repeated acquisition paradigm.
AB  - The glutamatergic (NMDA) and cholinergic neurotransmitter systems have been
      extensively implicated as neurochemical mediators of learning processes. These
      two systems may differentially affect learning; for example, although both the
      cholinergic antagonist scopolamine and the NMDA antagonist MK-801 reduced overall
      accuracy of rats in a 3-member repeated acquisition paradigm, the nature of the
      underlying error patterns produced by the two drugs differed significantly: rats
      administered scopolamine produced a pattern of skipping errors, while
      administration of MK-801 predominantly increased perseverative errors (Cohn et
      al., 1992). The present experiment extended that study to examine whether a more
      complex task, i.e. a 4-member repeated acquisition paradigm, would alter the
      nature of the error patterns resulting from administration of each drug, and
      whether NMDA itself would increase accuracy on the repeated acquisition paradigm.
      MK-801 (0.05-0.3mg/kg i.p.) significantly decreased overall accuracy in a dose
      dependent manner, and the rats produced a pattern of errors similar, although not
      identical to, that noted in the 3-member paradigm, including perseverative errors
      early in the sequence, but additional skipping errors at later points in the
      sequence. MK-801 dramatically decreased correct initiation of a sequence
      following an error at any point in the sequence. NMDA (10.0-30.0mg/kg) itself did
      not facilitate sequence acquisition, i.e. it did not affect overall accuracy.
      However, it was the only drug to increase the frequency of correctly reinitiating
      a sequence following an incorrect first or an incorrect second sequence member.
      Like MK-801, scopolamine (0.5-3.0mg/kg i.p.) also produced a decline in overall
      accuracy which was again achieved primarily through increased skipping errors.
      Scopolamine did not, however, interfere with correctly reinitiating a sequence
      either after successful completion of a sequence, or after an error. These
      findings suggest that cholinergic and glutamatergic compounds exert their effects
      on learning through different behavioral mechanisms.

PMID- 11224144
TI  - NMDA antagonists make learning and recall state-dependent.
AB  - Rats injected with either drug or saline were trained in a food-rewarded lever
      pressing task until they could complete an FR10 requirement within the first 120s
      of the session, and were then tested for the retention of this response under
      various treatment conditions. In this procedure, state-dependency occurred with
      ketamine, phencyclidine, MK-801 and CGS 19755; rats trained with any of these
      NMDA antagonists failed to show response transfer when tested with saline. Also,
      in rats trained with saline the response failed to transfer in tests with any of
      these drugs. The doses at which the failure to transfer occurred in drug-to
      saline tests, were approximately 3-fold lower than those at which the failure
      occurred in saline-to-drug tests. Even higher doses of these compounds were
      required to inhibit acquisition. The state-dependency which NMDA antagonists
      appear to produce in tests for saline-to-drug transfer, might constitute the
      mechanism whereby these compounds apparently disorganize the behavior of animals
      and, perhaps also, of humans. The data do not support the widely held notion that
      NMDA antagonists produce deficits in memory or retention; instead, at doses
      considerably lower than those impairing acquisition, NMDA antagonists produce a
      state upon which the recall of the newly learned response is dependent.

PMID- 11224146
TI  - Differential effects of cocaine on high and low response rates maintained with
      and without rate requirements.
AB  - Keypecking was maintained by a multiple (tandem random-interval 45-s,
      differential reinforcement of low rate 3-s) (tandem random-interval 45-s,
      differential reinforcement of high rate 0.2-s) schedule of food reinforcement in
      three pigeons. During non-drug sessions these schedule contingencies effectively
      controlled high and low response rates under approximately equal reinforcement
      frequencies. The behavioural effects of acute cocaine administration were
      assessed in the presence and absence of the response rate requirements (i.e. DRL,
      DRH contingencies). In the absence of response rate requirements cocaine
      administration consistently decreased high response rates. Low response rates
      tended to increase after the lower doses of cocaine, while they decreased
      consistently after the higher doses. High response rates decreased less after the
      lower doses of cocaine, in two of the three pigeons, when cocaine was
      administered in the presence of the rate requirements than when cocaine was
      administered in the absence of the rate requirements, while low rates increased
      less. Rate of reinforcement remained relatively constant across different lower
      doses of cocaine in the absence of high-rate requirements, but decreased in the
      presence of the high-rate requirements. Higher doses of cocaine consistently
      decreased reinforcement rate. These results support the notion that the
      behavioral effects of drugs may be a function of the extent to which response
      rates are directly controlled by schedule variables.

PMID- 11224145
TI  - An ethological analysis of the effects of diazepam and nitrazepam on the
      responses of female mice to anosmic males encountered in a novel arena.
AB  - The effects of acutely administered benzodiazepines have largely been validated
      in male animals, in spite of the fact that the majority of anti-anxiety drugs are
      prescribed for female patients. A study was carried out assessing the potential
      of female mice in the testing of the anxiolytic properties of drugs. Three doses
      (0.5, 1.0 and 2.0mg/kg) of the benzodiazepines diazepam and nitrazepam were given
      to individually-housed female Swiss mice before dyadic encounters with anosmic,
      group-housed males. Videotape analysis of the encounters, using an
      ethopharmacological technique, revealed suppressive effects of diazepam (1.0 and
      2.0mg/kg) and nitrazepam (all doses) on avoidance/flee, confirming the anxiolytic
      properties of these drugs. However, some doses of diazepam (2.0mg/kg) and
      nitrazepam (1.0mg/kg), greatly increased immobility with little effect on active
      behavioural elements. It is suggested that "immobility" does not simply measure
      sedation.

PMID- 11224147
TI  - Discriminative stimulus effects of the optical isomers of 3,4
      methylenedioxyamphetamine (MDA).
AB  - The isomers of 3,4-methylenedioxyamphetamine (MDA) functioned as discriminative
      stimuli in rats trained to discriminate either (-) MDA (1.25mg/kg) or (+) MDA
      (1.25mg/kg) from saline. Dose- and time-response curves indicated that drug lever
      selection occurred at doses of at least 1.00mg/kg of (-) MDA and 0.75mg/kg of (+)
      MDA and that drug-appropriate responding for both isomers was maintained for at
      least 90min. Cross-substitution was observed between the MDA isomers; both (+)
      and (-) 3,4-methylenedioxymethamphetamine (MDMA) also substituted completely for
      (+) and (-) MDA. The hallucinogens (+)-lysergic acid diethylamide (LSD) and (+/-)
      2,5-dimethoxy-4-methylamphetamine (DOM), substituted for (-) MDA; neither
      mescaline nor (+) amphetamine or cocaine had (-) MDA-like effects. LSD also
      substituted for (+) MDA; DOM, mescaline, (+) amphetamine and cocaine failed to
      have (+) MDA-like effects. The (-) but not the (+) MDA cue was blocked by the 5
      HT(2) antagonist pirenpirone; the dopamine (DA) antagonists SCH-23390 and (-)
      sulpiride had no effect on either the (-) or (+) MDA cues. When animals were
      trained to discriminate LSD (0.16mg/kg) or (+) amphetamine (1.0mg/kg) from
      saline, neither (-) MDA nor (+) MDA substituted completely. These results
      indicate that: (1) the stimulus effects of the isomers of MDA and MDMA are
      similar; (2) (-) MDA may be more hallucinogenic (or more accurately, LSD- or DOM
      like) than (+) MDA; (3) neither (+) nor (-) MDA has potent amphetamine-like
      effects; and (4) the effects of (-) MDA may be more serotonergic than those of
      (+) MDA.

PMID- 11224148
TI  - Effects of d-amphetamine, WIN 35,428, pentobarbital and morphine on schedule
      controlled responding in two inbred rat strains that differ in locomotor
      stimulatory effects of cocaine.
AB  - Behavioral effects of d-amphetamine, the cocaine analog, WIN 35,428, morphine,
      and pentobarbital were compared in NBR/NIH and F344CR1BR rats. Either nose-poke
      or lever-press responding was maintained under 3-min fixed-interval schedules of
      food presentation. The effects of morphine, WIN 35,428 and pentobarbital depended
      upon the rat strain studied: morphine increased nose-poke responding in NBR but
      not F344 rats; significant strain x dose interactions were observed with WIN
      35,428; and pentobarbital was more potent in decreasing nose-poke responding in
      NBR than in F344 rats. No strain differences were observed in the behavioral
      effects of d-amphetamine. There were also prominent differences in the effects of
      drugs that were related to the nature of the response requirement. In both rat
      strains, nose-poke responding was affected differently than lever-press
      responding by morphine, d-amphetamine, and WIN 35,428. Pentobarbital produced
      effects that were independent of the specified response topography. A global
      underlying difference in these rat strains cannot be identified at present to
      account for the diversity of findings. The behavioral effects of these drugs
      appear to be influenced by a host of interactive factors including the drug,
      strain of animal, the baseline response rate and physical dimensions of the
      response.

PMID- 11224149
TI  - Effects of methoxyflurane and flurothyl in mice trained to discriminate
      pentylenetetrazol from saline.
AB  - A procedure is described for training mice to discriminate 30mg/kg
      pentylenetetrazol (PTZ) from saline when lever pressing was maintained under a
      fixed-ratio 20 schedule of milk presentation. To define the pharmacological
      profile of the PTZ stimulus in mice, generalization testing was conducted with
      oxazepam and Ro 15-4513 (sarmazenil). Consistent with data obtained by others in
      rats, oxazepam (1mg/kg) blocked the PTZ stimulus whereas Ro 15-4513 substituted
      for PTZ, but only at a dose (2mg/kg) that also decreased rates of responding. The
      effects of both a depressant and excitatory vapor in this model were also
      determined. The volatile anesthetic methoxyflurane (1000-2000 ppm) blocked the
      discriminative stimulus effects of PTZ in a concentration-dependent manner, while
      the convulsant vapor flurothyl (900 ppm) produced greater than 90% PTZ-lever
      responding without disrupting rates of responding. The PTZ-like discriminative
      stimulus effects of flurothyl were dose-dependently blocked by oxazepam (0.03
      1.0mg/kg). As has been shown in numerous previous studies in rats, PTZ could be
      established as a discriminative stimulus in mice. PTZ discrimination could be
      blocked by a benzodiazepine agonist and shares some properties with a
      benzodiazepine inverse agonist. Substitution and antagonism studies can also be
      performed with vapors, illustrating the utility of this model for comparing their
      behavioral effects to those of more widely studied drugs.

PMID- 11224150
TI  - Discriminative-stimulus control by morphine in the pigeon under a fixed-interval
      schedule of reinforcement.
AB  - The stimulus control by morphine under a fixed-interval (FI) 180-s schedule of
      reinforcement was examined in five pigeons trained to discriminate 5.0mg/kg of
      i.m. morphine from saline. After training, dose-response relationships were
      determined for morphine, d-amphetamine, pentobarbital, fentanyl, and MK-801. At
      low doses of morphine, responding of individual subjects was predominantly on the
      saline-appropriate key. At intermediate doses responding occurred on both keys
      throughout the interval. Following doses of 5.6mg/kg and higher, responding on
      both keys was observed in the early portions of the interval with responding
      shifting to the morphine-appropriate key as the interval progressed. Thus, a
      graded dose-effect curve for morphine was obtained under the FI schedule. The
      fentanyl dose-effect curve was similar to that obtained with morphine, but the
      other test drugs were not generalized. Five other pigeons were trained to
      discriminate 5.0mg/kg of morphine from saline under a fixed-ratio (FR) 100
      schedule of reinforcement. During testing with morphine, responses were confined
      to the saline-appropriate key at 0.3 and 1.0mg/kg of morphine, but at higher
      doses responses were confined to the drug key. In contrast to the results
      obtained using the FI schedule, a quantal relationship for responding on the two
      keys was observed when a FR schedule was employed.

PMID- 11224151
TI  - Opposite effects of low and high doses of morphine on neural substrates of
      aversion in the inferior colliculus.
AB  - The inferior colliculus (IC) is a well known relay station for auditory pathways
      in the brainstem. Much evidence has implicated this structure as part of a brain
      system mediating aversive states, and changes in its functioning as responsible
      for the occurrence of audiogenic seizures. Rats were implanted with chemitrodes,
      devices which allow electrical stimulation and microinjections of drugs in the
      same brain sites. Stepwise increases in the intensity of electrical stimulation
      of the IC of rats placed inside a circular arena allowed the determination of
      thresholds for freezing and escape behavior. Morphine (10-40nmol) caused dose
      dependent increases in both aversive thresholds. A systemic injection of naloxone
      reversed the effects of morphine on the centrally induced aversive responses.
      These data suggest that neural substrates controlling defensive behavior in this
      structure are under opioid inhibitory control. Higher doses of morphine (80nmol)
      induced a non-naloxone reversible fearful hyper activity. It is suggested that
      opioid mechanisms exert an inhibitory control on the neural substrates of
      aversion in the IC and that high doses of morphine microinjected into IC cause
      pro-aversive actions probably through non-opioid mechanisms.

PMID- 11224152
TI  - Phencyclidine established as a discriminative stimulus using ethanol as a
      reinforcer.
AB  - Long-Evans hooded rats were initially trained to lever press, in standard,
      operant conditioning chambers, according to a fixed-ratio 1 (FR1) reinforcement
      schedule using 0.06ml deliveries of 8% w/v ethanol as the reinforcer, during
      daily Monday-Friday, 1h experimental sessions. Next, experimental sessions were
      reduced to 0.5h, the FR value was increased to 5, and the rats were trained to
      discriminate 2.0mg/kg s.c. phencyclidine (PCP) from saline vehicle using
      standard, drug discrimination training procedures, with 8% ethanol as the
      reinforcer. Following training, dose-response tests with PCP (0.1-4.0mg/kg),
      ketamine (0.1-18mg/kg), dexoxadrol (1.0-5.6mg/kg) and morphine (1.0-9.0mg/kg)
      were conducted. More PCP-lever presses were emitted than saline-lever presses at
      several doses of PCP, ketamine, and dexoxadrol, indicating generalization from
      the 2.0mg/kg PCP stimulus. When morphine was tested, more saline-lever than PCP
      lever presses were made, and percent PCP-lever pressing never exceeded an average
      of 12% at any dose tested. This study demonstrates that one drug of abuse, PCP,
      can serve as a discriminative stimulus when another drug of abuse, ethanol,
      serves as the reinforcing stimulus, and is the first explicit laboratory
      demonstration of drug discriminative stimulus control during drug self
      administration.

PMID- 11224153
TI  - Behavioral pharmacology of abecarnil in baboons: self-injection, drug
      discrimination and physical dependence.
AB  - The behavioral effects of abecarnil, a beta-carboline which has been suggested to
      function as a partial and/or selective agonist at the benzodiazepine receptor,
      were assessed in baboons. In a chronic administration study, 100mg/kg/day
      abecarnil for 6-8 weeks produced few signs of sedation: lip droop and intention
      tremor were observed in two of the four baboons. Flumazenil administration
      (5mg/kg, i.m.) on day 8 of chronic abecarnil produced only a mild precipitated
      benzodiazepine withdrawal syndrome. Vehicle substitution after 6-8 weeks of
      chronic abecarnil produced transient signs of a mild withdrawal syndrome,
      including decreased food intake, but did not produce vomiting, twitches/jerks or
      seizures. In a self-injection study, abecarnil (0.032-1.0mg/kg/injection) did not
      maintain rates of self-injection above vehicle control levels; higher rates of
      self-injection were maintained in the same animals by cocaine
      (0.32mg/kg/injection) and triazolam (0.01mg/kg/injection). The highest i.v.
      abecarnil dose (1.0mg/kg/injection) produced sedation and ataxia in two of the
      three baboons. In a drug discrimination study, generalization from lorazepam
      training conditions (1.8mg/kg, p.o.) to abecarnil was an increasing function of
      dose, and maximal drug lever responding occurred reliably in all baboons 5h after
      10-32mg/kg, p.o. abecarnil administration. Flumazenil (0.32mg/kg, i.m.), given 4h
      after abecarnil, completely antagonized the abecarnil stimulus in test sessions
      1h later. The present experiments show that the behavioral profile of abecarnil
      is clearly distinguisable from that of benzodiazepines.

PMID- 11224154
TI  - The effect of d-fenfluramine on intake of carbohydrate supplements is influenced
      by the hydration of the test diets.
AB  - The effect of d-fenfluramine on carbohydrate intake in the rat has been
      investigated using a dietary paradigm in which a pure carbohydrate supplement is
      presented in addition to the normal balanced chow diet. This experimental
      strategy has been used as an alternative to the macronutrient selection model in
      an attempt to increase the sensitivity of the measurement of drug effects on
      carbohydrate intake. This issue is important because of the postulated
      theoretical relationship between brain serotonin (5-HT) and carbohydrate intake.
      The effect of d-fenfluramine was dependent upon the texture and density of the
      supplement (hydrated vs. non-hydrated) and upon the nature of the carbohyhdrate
      employed - either sucrose (sweet-tasting) or Polycose (bland-tasting). Selective
      carbohydrate suppression, by d-fenfluramine, was detected (as predicted by the 5
      HT/carbohydrate theory) but only under specific environmental conditions, namely
      hydrated chow supplemented with dry Polycose. Therefore, suppression of
      carbohydrate may depend, not on any inherent biological link between carbohydrate
      consumption and brain 5-HT activity, but on a shift in relative preference for
      the diet choices available.

PMID- 11224155
TI  - Reinforcement loss and behavioral tolerance to d-amphetamine: using percentile
      schedules to control reinforcement density.
AB  - Two procedures were used to examine the impact of reinforcement loss on the
      development of behavioral tolerance to the effects of d-amphetamine on control
      over response number in rats. Under both procedures, trials consisted of at least
      one left-lever press followed by a single right-lever press. Consecutive left
      lever presses on each trial comprised a "run". A targeted percentile schedule
      provided reinforcement if the current run length was closer to the target length
      (12) than two-thirds of the most recent 24 runs. This procedure differentially
      reinforced runs around 12 while holding reinforcement probability constant at
      0.333. A second group acquired the differentiation under the percentile schedule,
      but was then shifted to a procedure which yoked reinforcement probability by
      subject and run length to that obtained under asymptotic percentile schedule
      performance. The two procedures generated roughly comparable, but not identical,
      control run lengths, response rates, reinforcement probabilities and
      reinforcement rates. Only under the yoked procedure, however, did drug-induced
      disruptions in run length produce decreases in reinforcement density. Acute
      administration of amphetamine produced dose-related decreases in run length and
      overall response rate under both procedures. Daily pre-session administration of
      1.7mg/kg amphetamine persistently suppressed run length under the percentile
      procedure, but not under the yoked procedure. Run lengths under the latter
      gradually increased with repeated amphetamine to a level equal to or slightly
      below baseline levels. Response rate was suppressed initially, and tolerance
      developed inconsistently to this effect in both groups. Dose-effect curves
      obtained when doses of amphetamine were substituted for the chronic dose showed a
      larger shift to the right with the yoked than percentile group for run length,
      and a similar but smaller effect for overall response rate. These results
      indicate that reinforcement loss substantially contributes to the development of
      tolerance to the behavioral effects of amphetamine, even when the comparison
      behaviors are generated by reinforcement contingencies that under non-drug
      conditions control very similar rates and patterns of behavior and reinforcement.
      Future comparison of acute and chronic drug effects on behaviors maintained by
      the percentile and yoked procedures may prove very helpful in illuminating drug
      behavior interactions and the dynamic interrelations typically engendered by more
      traditional reinforcement schedules.

PMID- 11224156
TI  - Factors influencing self-administration of, and subjective response to, placebo
      marijuana.
AB  - Self-administration of, and subjective response to, placebo marijuana were
      studied in two groups of regular marijuana smokers. One group received the drug
      under a set of instructions that informed them that the marijuana was active
      (deceptive administration); the other group was informed that the marijuana might
      be inactive (double-blind administration). Subjects were allowed to smoke placebo
      marijuana freely for 60min during four identical weekly sessions. Subjects smoked
      an average of 6.0 half-length cigarettes per session, resulting in a mean
      increase in expired air carbon monoxide of 14.6 ppm. Placebo self-administration
      did not change significantly across the four sessions. Smoking was associated
      with marijuana-like subjective effects. Subjects in the deceptive administration
      group smoked more placebo marijuana and reported a greater subjective response
      than the other group during the first session only. Several anamnestic factors
      (drug use history, current pattern of marijuana use, dimensions of personality)
      correlated with the amount of placebo self-administered, and subjects with less
      marijuana experience tended to report stronger subjective responses to the
      placebo. These results demonstrate the importance of including a placebo control
      when studying the reinforcing effects of marijuana and identify some factors that
      might predict placebo responses to marijuana or other drugs.

PMID- 11224157
TI  - Effects of SKF 38393 and quinpirole on aggressive, motor and schedule-controlled
      behaviors in mice.
AB  - The respective roles of D1 and D2 dopamine receptors in mediating motor
      functions, aggressive behaviors and reinforcement processes have not been
      specified. The present experiments examined conditioned and unconditioned
      behaviors of mice under different demands and reinforcing contingencies. We
      compared the behavioral effects of the D2 agonist quinpirole and the D1 partial
      agonist SKF 38393 on motor activities, aggressive behaviors and schedule
      controlled responses in male mice that were either pair-housed with a female for
      4 weeks or singly-housed. Singly-housed mice were found to be more active than
      pair-housed mice both when alone in the home cage and in the presence of a male
      intruder. However, the effects of both quinpirole and SKF 38393 were
      substantially similar for both singly- and pair-housed mice. Quinpirole decreased
      motor activity, aggressive behavior, and schedule-controlled responding. In
      contrast, SKF 38393 decreased schedule-controlled responding at doses that did
      not affect either motor or aggressive behaviors. The relative behavioral
      specificity of SKF 38393 suggests that D1 activation alters the temporal
      patterning of behavior, while D2 activation appears to cause a more general
      suppression of behavior in mice.

PMID- 11224158
TI  - Comparative study of typical neuroleptics, clozapine and newly synthesized
      clozapine-analogues: correlations between neurochemistry and behaviour.
AB  - While neuroleptic therapy with classical compounds has frequently been associated
      with extrapyramidal side effects, clozapine has revealed an interesting
      antipsychotic profile without producing any clearcut motor side effects. However,
      some adverse reactions remained that stimulated the search for improved
      antipsychotic agents. The aim of this study was to characterize the behavioural
      and neurochemical profiles of typical neuroleptics (chlorpromazine, haloperidol),
      clozapine, and four newly synthesized clozapine-analogues. Affinity for
      dopaminergic (D1,D2), serotonergic (5-HT(2)) and cholinergic (muscarinic)
      receptors were measured and the ratios of these different binding affinities were
      determined and correlated with the behavioural effects of the drugs in a complex
      temporal regulation task in the dog. The four clozapine-analogues showed most of
      the behavioural characteristics previously described for neuroleptics and their
      neurochemical profile, particularly their 5-HT(2)/D2 pKi ratio, was compatible
      with an atypical antipsychotic effect. Among these drugs, JL5 and JL13 showed a
      high degree of similarity with clozapine. Like clozapine, they did not induce
      catalepsy and stereotypy/hyperkinesia. Moreover, other motor effects were also
      reduced (ataxia, akinesia, dystony). and tremor and sialorrhea were completely
      absent with these two molecules.

PMID- 11224159
TI  - Opioid-induced response-rate decrements in pigeons responding under variable
      interval schedules: reinforcement mechanisms.
AB  - Opioid drugs may produce some of their behavioral effects by altering the
      effectiveness of reinforcing events. The present investigation examined effects
      of two opioids (methadone and buprenorphine) on pigeons' key-pecking. Different
      reinforcement rates were arranged using five variable-interval (VI) food
      presentation schedules, permitting an application of Heyman's Matching Law
      analysis and Nevin's Resistance to Change Hypothesis to behavioral actions of
      opioid drugs. Key-pecking by four pigeons was reinforced by 3-s access to mixed
      grain under a five component multiple VI schedule. VI values used were 5, 10, 30,
      75 and 150s. Each component was in effect for 5min followed by 1min of darkness.
      Peck rates were high under the VI5-s and VI10-s schedules. As the mean interval
      value increased, peck rates decreased. Methadone (0.5, 1.5, 2.5, 3.75, and
      5.0mg/kg) and buprenorphine (0.25, 0.5, 1.0, 3.0, and 5.0mg/kg), administered
      30min prior to experimental sessions, dose dependently decreased peck rates in
      all subjects. Peck rates under longer VI schedules (75 and 150s) tended to be
      more greatly disrupted than those maintained under shorter VI schedules (e.g.
      10s). Dose-by-dose analysis of key-pecking rate changes under each schedule, and
      analysis of drug-induced changes in Matching Law parameters suggest that peck
      rate decreases resulted, in part, from decrements in the reinforcer's ability to
      maintain behavior.

PMID- 11224160
TI  - NMDA antagonists disrupt timing behaviour in rats.
AB  - The behavioural effects of six compounds with N-methyl-D-aspartate (NMDA)
      antagonist properties were compared on the responding of rats maintained by a
      differential reinforcement of low rate 15s (DRL-15s) schedule. This schedule
      requires that responses be temporally spaced in order to be reinforced (timing
      behaviour). The number of reinforcers obtained was decreased by the non
      competitive NMDA antagonists phencyclidine, dizocilpine and memantine, by the
      competitive NMDA antagonist CGS 19755, by the antitussive drug dextromethorphan,
      but not by the polyamine site antagonist eliprodil (SL 82.0715). Small increases
      in response rates were produced by phencyclidine and memantine, and dizocilpine
      gave rise to very marked increases in rates. CGS 19755, eliprodil and
      dextromethorphan only decreased rates of responding at high doses. Analysis of
      drug action in terms of inter-response times (IRT) showed that, except for
      eliprodil, all compounds shifted the peaks of the IRT distributions to the left.
      The percentage of short IRTs (response bursts) showed statistically significant
      increases after administration of dizocilpine, phencyclidine, memantine and CGS
      19755. These results show that timing behaviour in rats is disturbed by several
      NMDA antagonists, although eliprodil, while decreasing responding at high doses,
      did not disrupt efficient timing.

PMID- 11224161
TI  - Quantification of tremor sensitivity and inhibition of exploratory behaviour
      during alcohol withdrawal in rats.
AB  - Rats given a 10% (v/v) alcohol liquid diet over two weeks reached high blood
      alcohol levels of around 200mg/dl. Discontinuation of the alcohol intake resulted
      within 6h in several withdrawal reactions including a tremorogenic activity and a
      reduction in exploratory behaviour in novel environments. The tremorogenic
      activity of the alcohol withdrawal could be quantified, using a piezo-film
      technique, in terms of a supersensitivity to both an inactive and a moderately
      active dose of the tremorogenic compound harmine. As compared to controls, the
      rats in alcohol withdrawal revealed more frequent tremor after both 5 and 10mg/kg
      harmine. The supersensitivity to harmine-induced tremor started within 6h after
      alcohol withdrawal and remained present with 10mg/kg harmine for up to 48h. The
      supersensitivity was independent of the length of the tremor bursts used to
      quantify harmine-induced tremor. Alcohol withdrawal also resulted in an
      inhibition of exploratory behaviour in a neutral two-chamber box. Both in terms
      of the number of transits into the open field as well as the time spent in the
      open area, rats in alcohol withdrawal were significantly less active than control
      animals. The reduced exploration started within 6h after withdrawal and remained
      present for up to 24h after the last alcohol intake. These results indicate that
      both alcohol withdrawal-induced sensitivity to tremorogenic agents and inhibition
      of exploratory behaviour can be quantified over time, allowing the
      pharmacological mechanisms involved to be studied.

PMID- 11224162
TI  - Agonist and antagonist activity of low efficacy D2 dopamine receptor agonists in
      rats discriminating d-amphetamine from saline.
AB  - The ability of the low efficacy D2 agonists preclamol and SDZ 208-911 to both
      antagonise, and substitute for, the d-amphetamine discriminative cue was
      investigated in rats trained to discriminate d-amphetamine (0.5mg/kg) from
      saline. All doses of preclamol (2.0-16.0mg/kg) and SDZ 208-911 (0.125-1.0mg/kg)
      only partially antagonised d-amphetamine discrimination. In contrast, the lower
      efficacy D2 agonist SDZ 208-912 completely blocked the cueing properties of d
      amphetamine. Preclamol (4.0 and 16.0mg/kg) and SDZ 208-911 (1.0mg/kg) also
      partially substituted for d-amphetamine. In an additional study, the former drug
      enhanced the discriminative effects of a low dose of d-amphetamine (0.125mg/kg),
      whilst antagonising the effects of the training dose. Preclamol also partially
      antagonised the ability of the selective D2 agonist quinpirole (0.125mg/kg) to
      substitute for d-amphetamine. In contrast to the drug discrimination findings,
      preclamol completely antagonised the locomotor hyperactivity induced by acute d
      amphetamine, in animals which had received the same long-term d-amphetamine
      treatment as the drug discrimination rats. The present findings reveal that
      preclamol and SDZ 208-911 can exert both agonist and antagonist activity in
      animals trained to discriminate d-amphetamine from saline. This partial agonist
      profile is probably due to the low efficacy D2 agonists interacting with a
      postsynaptic D2 receptor population possessing a higher response capability than
      those D2 receptors mediating d-amphetamine-induced locomotor hyperactivity.

PMID- 11224163
TI  - Anxiogenic-like effects of fluprazine and eltoprazine in the mouse elevated plus
      maze: profile comparisons with 8-OH-DPAT, CGS 12066B, TFMPP and mCPP.
AB  - It has recently been proposed that the "serenic" (antiaggressive) agents,
      fluprazine and eltoprazine, may enhance fear/anxiety reactions in laboratory
      rodents. In the present study, the influence of these compounds (1.25-10.0mg/kg)
      on anxiety-related behaviour in male mice was examined in the elevated plus-maze
      test. For comparative purposes, the effects of 8-OH-DPAT (0.01-1.0mg/kg) CGS
      12066B (1.25-10mg/kg), TFMPP (0.63-5.0mg/kg) and mCPP (0.5-4.0mg/kg) were also
      assessed. Behavioural analysis incorporated not only traditional parameters but
      also several novel measures of defensive behaviour (i.e. "risk assessment"). The
      selective 5-HT(1A) agonist 8-OH-DPAT produced effects only at 1.0mg/kg, with
      evidence of an anxiolytic/sedative action at this dose. In the absence of other
      behavioural changes, CGS 12066B (a selective 5-HT(1B) agonist) caused a
      preferential and dose-dependent (2.5-10.0mg/kg) stimulation of closed arm
      entries, an effect also seen with low doses of TFMPP (0.63mg/kg) and the serenics
      (1.25-2.5mg/kg). In addition, both TFMPP and mCPP (5-HT(1C/1B) agonists) induced
      dose dependent anxiogenic-like effects over the dose ranges tested, with the most
      pronounced changes observed on measures of risk assessment. The profiles of
      fluprazine and eltoprazine on plus-maze behaviour were not only similar to one
      another but, on most parameters, were also remarkably like those observed with
      TFMPP and mCPP. These data question the behavioural selectivity of the serenics
      and further support the proposal that these compounds may potentiate anxiety.
      Findings are discussed in relation to underlying receptor mechanisms, and the
      utility of a more ethological approach to the analysis of behaviour on the
      elevated plus-maze.

PMID- 11224164
TI  - Choice between cocaine and food by rhesus monkeys: effects of conditions of food
      availability.
AB  - The present experiment was designed to examine the effects of the conditions of
      food availability on choice between cocaine and food in rhesus monkeys. Monkeys
      (n = 3), maintained at approximately 90% of their free-feeding weights, were
      trained in a discrete-trials choice procedure and allowed to choose between
      intravenous injections of cocaine (0.03-1.0mg/kg/injection) and food delivery (4
      pellets; 1g/pellet) during daily 7-h sessions. When food was available both
      within the session and by supplemental post-session feeding, the frequency of
      cocaine choice increased in a dose-related manner for all monkeys. When
      supplemental post-session feeding was eliminated (i.e. food was only available
      within the session) the cocaine dose-response function was shifted to the right
      and down relative to that found initially. However, changes in the frequency of
      cocaine choice did not vary consistently with changes in body weight. Thus, these
      results suggest that the reinforcing efficacy of cocaine can be modified by
      changing the conditions of availability of an alternative non-drug reinforcer.

PMID- 11224165
TI  - TRH activates mesolimbic dopamine system: behavioural evidence.
AB  - The effect of TRH pretreatment on locomotor activity and stereotypy induced by d
      amphetamine was examined in rats. The results show that TRH potentiates d
      amphetamine-induced locomotor activity, but not d-amphetamine-induced stereotypy,
      suggesting that this neuropeptide selectively activates the mesolimbic dopamine
      system.

PMID- 11224166
TI  - Multiple-choice procedure: an efficient approach for investigating drug
      reinforcement in humans.
AB  - Two experiments demonstrated the efficiency of assessing drug reinforcement in
      humans by using a novel multiple-choice procedure. The distinguishing
      characteristic of the procedure is that it arranges intermittent reinforcement
      for choices between pairs of potential reinforcers. The procedure has three key
      operations: (1) a subject is exposed to the potential reinforcers; (2) a subject
      then makes two or more choices on a questionnaire; for each choice, the subject
      is required to choose one of two potential reinforcers (e.g. drug vs. drug
      choices and/or drug vs. money choices); and (3) subsequently only one of the
      choices, randomly selected, is reinforced. In the present experiments, two
      variations of the multiple-choice procedure were evaluated in twelve male drug
      abusers. Both experiments assessed the reinforcing effects of three drug
      conditions (200 and 400) mg/70kg pentobarbital and placebo) which were presented
      no more often than every to other day. The experiments demonstrated dose-related
      choice of pentobarbital over money as well as choice of a higher dose of
      pentobarbital over a lower dose or placebo. Orderly data were generated with a
      single-session exposure to each drug condition. Multiple-choice procedures should
      have applicability, not only to the investigation of drug reinforcement, but also
      to the study of non-drug reinforcement in humans.

PMID- 11224167
TI  - Disruption of conditioned reaction time performance by dopamine receptor
      antagonists in the rat.
AB  - The effects of the neuroleptics haloperidol, cis-flupenthixol and chlorpromazine,
      and the selective dopamine (DA) receptor antagonists raclopride and SCH 23390,
      were assessed in a conditioned reaction time task. In this operant task, rats
      were required to hold down a lever for a randomly determined hold duration (0.5
      2.0s) and to release the lever within 1s of a light cue to obtain food
      reinforcement. All drugs dose-dependently reduced the total number of lever
      presses and the number of rewarded responses, and all but chlorpromazine produced
      an abrupt cessation of responding before the end of the experimental session.
      However, there were variations in the ability of these drugs to impair lever
      release performance. Chlorpromazine and the selective D2 antagonist raclopride
      significantly elevated rewarded and total reaction times. The former drug also
      increased the number of delayed responses (i.e. those occurring with a latency of
      greater than 1s) and reduced the percentage of rewarded responses occurring
      following light onset (percentage success), whilst raclopride also increased
      delayed reaction times. Haloperidol failed significantly to influence rewarded
      and total reaction times, as well as the percentage success measure. However, the
      lowest dose of haloperidol increased the number of delayed responses, indicating
      a subtle impairment of lever release performance. cis-Flupenthixol and the
      selective D1 antagonist SCH 23390 failed significantly to influence any aspect of
      lever release performance. Only haloperidol and cis-flupenthixol increased the
      time rats took to move from the lever to the food hopper, whilst all drugs
      increased the time taken to return to the lever. Although feeding animals prior
      to the experimental session, or removing food pellets from the dispensers during
      the session, reduced overall response levels, the former did not influence any
      reaction time measure, whilst extinction only reduced percentage success. The
      present findings reveal that certain DA receptor antagonists impair conditioned
      lever release performance. However, this reaction time deficit is not obtained
      with all DA receptor antagonists, despite their consistent effects on other
      aspects of performance in the task.

PMID- 11224168
TI  - Increased ethanol choice in social drinkers following ethanol preload.
AB  - This study showed that normal social drinkers were more likely to consume ethanol
      after receiving a "priming" (preload) dose of ethanol. Twenty-eight non-problem
      drinkers (average consumption 9 drinks/week) participated in a six-session,
      double-blind choice procedure. On the first two sessions they sampled beverages
      containing ethanol (0.8g/kg) or placebo (mix alone), between which they would
      choose on subsequent choice sessions. On the third session ("dummy" choice
      session) subjects were first asked to indicate verbally which beverage they
      preferred. If they chose the ethanol-containing beverage the experimenter
      negotiated with each subject to determine the minimum amount of money (from $1 to
      $30) needed to switch his or her choice from ethanol to placebo. Once this amount
      was determined it remained fixed for the subsequent three preload/choice
      sessions. Thus, on choice sessions subjects chose between the beverage which
      contained ethanol, and placebo plus the amount of money established in Session 3.
      On the preload/choice test sessions (Sessions 4-6) subjects received preloads of
      ethanol (0, 0.25 or 0.5g/kg) 1h before being given the choice between the sampled
      ethanol beverage and the placebo beverage plus money. The frequency of ethanol
      choice was the primary dependent variable. Subjective drug effects, including
      ratings of desire for the sampled substances, were also measured. Twenty subjects
      initially chose ethanol on Session 3 and switched their choice with a monetary
      incentive. Of these 20 subjects, four chose ethanol after the placebo preload,
      seven chose ethanol after the low-dose ethanol preload, and 11 chose ethanol
      after the higher ethanol preload (significant linear trend, Mantel-Haenszel test,
      p < 0.03). Ratings of desire for the ethanol-containing beverage increased after
      the higher preload. These results suggest that ingestion of a moderate dose of
      ethanol increases the tendency to continue drinking, even among normal social
      drinkers.

PMID- 11224169
TI  - In a low-versus high-dose drug discrimination task, random reinforcement in one
      drug state alters discriminative control only in that state.
AB  - This study investigated the effects of introducing random reinforcement training
      after a drug discrimination between 3.0 and 15.0mg/kg chlordiazepoxide had been
      acquired in rats; a two-lever food-rewarded operant procedure was used. Matched
      on the basis of dose-generalization test data, two dose-equisensitive groups were
      formed (A and B). Group A received 30 daily saline injections, which were
      followed by a random reinforcement session during which either left or right
      lever presses were reinforced on a probabilistic basis on each of the trials
      comprising a session. Group B received saline but no training or testing during
      this period. Subsequent testing revealed that responding conditioned to the low
      dose training condition, but not to the high-dose training condition, was
      significantly changed in Group A. The randon reinforcement data further suggested
      that Group A did not discriminate saline from the low training dose. In
      Experiment 2, Group B of Experiment 1 was submitted to 30 random reinforcement
      training sessions, each preceded by a high training dose administration. Data
      showed that responding to the high dose, but not the low dose, was changed. For
      both experiments, chlordiazepoxide dose generalization following reacquisition
      was similar to that obtained before the random reinforcement phase. The findings
      indicate that the response pattern changed only for the stimulus condition
      present during random reinforcement. The random reinforcement manipulation did
      not disrupt the original discrimination between the high-and low-dose conditions.

PMID- 11224170
TI  - Behaviour in the novel environment predicts responsiveness to d-amphetamine in
      the rat: a multivariate approach.
AB  - The behaviour of rats in a novel environment was studied using a rapid time
      sampling observation procedure followed by a principal component analysis (PCA)
      of the data. This approach revealed that novel environment behaviour can be
      described by two factors or principal components. The first factor comprised
      rearing, sniffing-up, ambulation and locomotion (photocell counts), and was
      termed "Escape". The second factor, which had high positive loadings of sniffing
      down and locomotion and a high negative loading of immobility, was termed
      "Exploration". The scores of individual rats on the "Escape" factor predicted the
      stimulatory effect of acutely administered d-amphetamine (1.5mg/kg) on
      unconditioned behaviour. "Escape" high responders (HRs) showed more behavioural
      stimulation than "Escape" low responders (LRs). However, the locomotor
      stimulatory response of both groups increased after long-term, periodic
      administration of d-amphetamine and drug discrimination training, such that the
      level of drug-induced locomotor activity was now equivalent for the two groups.
      The same rats were tested twice with various doses of d-amphetamine after being
      trained to discriminate this drug (0.5mg/kg) from saline. "Escape" HRs were less
      sensitive than "Escape" LRs to the discriminative effects of 0.125-0.25mg/kg d
      amphetamine. In contrast to these findings, "Exploration" HRs and LRs were not
      different on any of the dependent measures described above. These results are
      discussed in relation to the possibility that "Escape" factor scores are an
      indication of an animal's responsivity to novelty-induced stress. If this is the
      case, then animals which are more susceptible to the effects of novelty stress
      are more sensitive to the locomotor stimulating effects of acute d-amphetamine,
      but less sensitive to the cueing properties of low doses of this drug.

PMID- 11224171
TI  - Ethanol effects in pigeons trained to discriminate MK-801, PCP or CGS-19755.
AB  - The non-competitive N-methyl-D-aspartate (NMDA) antagonists MK-801, PCP and
      ketamine have recently been found to produce full drug-appropriate responding in
      pigeons trained to ethanol (1.5g/kg) in a two-key operant drug discrimination
      procedure. In the present study, ethanol (0.56-3.2g/kg i.g.) was administered to
      pigeons trained to discriminate MK-801 (0.18mg/kg, n = 5), PCP (1.0mg/kg, n = 4)
      or the competitive NMDA antagonist CGS-19755 (1.8mg/kg, n = 4) from vehicle. Up
      to doses that caused large reductions in response rates, ethanol produced only
      vehicle-appropriate responding in the pigeons trained to PCP and only low levels
      of drug-appropriate responding in pigeons trained to MK-801 and CGS-19755. The
      present results suggest there could be asymmetric generalization between the
      discriminative stimulus effects of i.g. ethanol and NMDA antagonists.

PMID- 11224172
TI  - Generalization of behavioral history across responses in the reversal of the
      effects of cocaine and d-amphetamine on the punished behavior of squirrel
      monkeys.
AB  - Previous research has demonstrated that the effects of d-amphetamine on punished
      lever pressing of squirrel monkeys are modified by an avoidance history in which
      lever pressing postpones shock. In the present experiment generalization of
      behavioral history across responses was assessed by determining the effects of d
      amphetamine and cocaine on punished lever pressing of squirrel monkeys before and
      after exposure to an avoidance procedure in which a chain-pulling response
      postponed shock. The punishment schedule consisted of a fixed-interval 5-min
      schedule of food delivery in which every 30 lever presses produced a 5-mA
      electric shock. During avoidance sessions each chain pull postponed shock
      delivery for 25s; in the absence of chain pulling, shocks occurred every 5s. Only
      a single response manipulandum was present in each phase. Punished lever pressing
      was initially unaltered or decreased by d-amphetamine and cocaine. Following the
      chain-pull avoidance history, however, d-amphetamine produced dose-dependent
      increases in the punished lever pressing of all three monkeys at several doses
      that formerly did not alter or reduce responding; a similar pattern of results
      was obtained when cocaine was administered to two of the subjects. The effects of
      d-amphetamine and cocaine on punished lever pressing were subsequently determined
      within the context of a multiple schedule of lever-press punishment and chain
      pull avoidance, with both manipulanda present simultaneously. The effects of the
      drugs on punished lever pressing within the multiple schedule were similar to
      their initial, pre-avoidance effects for the two monkeys whose responding was
      increased by both drugs in the preceding, post-avoidance phase. Chain pulling
      during the punishment component was dose-dependently increased, suggesting that
      chain pulling during punishment reduced the opportunity to exhibit increases in
      punishing lever pressing. The remaining monkey's punished lever pressing was
      increased by both drugs within the context of the multiple schedule. This
      experiment demonstrates that avoidance-dependent upward shifts in the dose
      response curves of d-amphetamine and cocaine can occur when the punishment and
      avoidance responses differ, and that original effects can be partially restored
      when both responses are available simultaneously. The results suggest that
      generalization across responses of the effects of a critical behavioral history
      may be a general property of behavioral history phenomena within behavioral
      pharmacology. These findings underscore the generality and importance of
      behavioral history as a modulatory influence on the effects of abused drugs.

PMID- 11224173
TI  - The role of monoamine uptake in the discriminative stimulus effects of cocaine
      and related compounds.
AB  - The involvement of monoamine neurotransmitter uptake in the discriminative
      stimulus effects of cocaine was examined in rats (n = 48) trained to discriminate
      10mg/kg of this substance from saline in a two-level, water-reinforced (FR 20),
      drug discrimination situation. Compounds that act primarily by inhibiting
      dopamine (DA) uptake substituted for the cocaine cue; the order of potency was
      mazindol > nomifensine > GBR 12909 > bupropion, although efficacy was lowest with
      GBR 12909. Desipramine, which inhibits norepinephrine (NE) uptake, substituted
      partially for cocaine while two drugs that inhibit serotonin (5-HT) uptake,
      citalopram and fluoxetine, did not mimic cocaine. When given in combination with
      cocaine, cis flupenthixol and SCH 23390 reduced responding on the cocaine
      appropriate lever significantly and to a greater extent than either haloperidol,
      (+/-) sulpiride or (-) sulpiride; neither (+) sulpiride nor metergoline had
      significant effects. Cocaine substitutions with DA uptake inhibitors were also
      attenuated to varying extents by cis-flupenthixol, SCH 23390 and haloperidol, but
      not by metergoline. These data, in conjunction with results reported previously,
      suggest that inhibition of DA uptake is involved to a greater extent than either
      NE or 5-HT uptake in the discriminative stimulus properties of cocaine and
      related compounds. Since both the cocaine cue and its substitution by DA uptake
      inhibitors appear to be blocked most effectively, reliably and potently by
      compounds that act either non-selectively at DA receptors (cis-flupenthixol) or
      primarily at D1 receptors (SCH 23390), D1 mechanisms may play a particularly
      important role in the neuronal substrates of these behavioral effects.

PMID- 11224174
TI  - The benzodiazepine receptor partial agonists, bretazenil (Ro 16-6028) and Ro 17
      1812, affect saccharin preference and quinine aversion in the rat.
AB  - A previous experiment had shown that the benzodiazepine receptor (BZR) agonist,
      clonazepam, selectively increased the consumption of a 0.05% sodium saccharin
      solution without change in water intake, in a two-choice preference test. The
      first aim of this study was to investigate the effects of two benzodiazepine
      receptor partial agonists, bretazenil (Ro 16-6028) and Ro 17-1812, in the same
      test. The results showed that both drugs produced effects similar to those
      observed earlier with clonazepam. The second aim was to investigate the effects
      of the two compounds on consumption of a 0.005% quinine solution in a two-choice
      test. Both drugs increased the consumption of the quinine solution without
      alteration in water intake. In addition, in separate single-choice acceptance
      tests, both drugs significantly increased the consumption of a familiar, highly
      palatable 3% sucrose solution. These data are considered in relation to
      alternative hypotheses for BZR-mediated effects in choice tests.

PMID- 11224175
TI  - Muscimol infused into the entorhinal cortex prior to training blocks the
      involvement of this area in post-training memory processing.
AB  - Muscimol infusions into the entorhinal cortex (ERC) have previously been reported
      to impair the retention of passive avoidance learning, but only when infusions
      were delayed until 90min after training. In the present study, three experiments
      were carried out to examine further the effects of muscimol infusions into the
      ERC prior to training. In Experiment 1, muscimol infusions prior to training had
      no effect on retention, confirming earlier findings, but blocked the amnestic
      effect of a second muscimol infusion 90min post-training. In Experiment 2,
      muscimol infusions prior to training blocked the improvement of retention
      normally seen following a second training trial 2h after the first. In Experiment
      3, the technique of summation of performance across training trials was used to
      confirm that the direct effects of muscimol infusions lasted less than 2h. The
      results indicate that the GABA-ergic mechanism in the ERC is normally involved in
      the formation of memory for passive avoidance, but if the ERC is inactivated at
      the time of training, memory formation is diverted to other structures, which
      appear less capable of integrating consecutive memories across time.

PMID- 11224176
TI  - Conditioned place aversion induced by 5-HT(1C) receptor antagonists.
AB  - A place-conditioning procedure was used to investigate the affective properties
      in rats of non-selective serotonin receptor antagonists (mianserin, eltoprazine
      and ketanserin) differing from each other by their affinity for 5-HT(1C) and 5
      HT(2) receptors among others. At the highest dose tested (10mg/kg,i.p.), the
      mixed 5-HT(1C)/5-HT(2) receptor antagonist mainserin produced a significant place
      aversion to the drug-paired compartment. The 5-HT(1B) receptor agonist/5-HT(1C)
      receptor antagonist eltoprazine induced a place aversion at doses of 1 and
      10mg/kg. In contrast, the 5-HT(2) receptor antagonist ketanserin produced neither
      place aversion nor place preference at the doses tested (1 or 10mg/kg, i.p.). The
      preferential 5-HT(1C) receptor agonist mCPP was given prior to mianserin or
      eltoprazine administration. mCPP (1mg/kg, i.p.) significantly prevented the
      conditioned place aversion produced by mianserin or eltoprazine, without
      exhibiting any aversive or rewarding effect by itself. These results suggest that
      acute 5-HT(1C) receptor blockade is involved in the production of aversive
      effects of mianserin and eltoprazine.

PMID- 11224177
TI  - Effects of ethanol and NMDA antagonists on operant behavior in ethanol withdrawal
      seizure-prone and-resistant mice.
AB  - The acute effects of ethanol (EtOH) on fixed-ratio performance were studied in
      separate lines of mice selectively bred for differences in severity of handling
      induced convulsions following withdrawal from EtOH. Because modulation of N
      methyl-D-aspartate (NMDA) receptors has been implicated in production of the
      acute and withdrawal-induced effects of EtOH, we also tested NMDA and three NMDA
      antagonists. Withdrawal seizure-resistant (WSR2) mice were more sensitive to the
      response rate-decreasing effects of EtOH than were withdrawal seizure-prone
      (WSP2) mice. Similar to EtOH, NPC 12626 (a competitive NMDA antagonist) and
      phencyclidine (a non-competitive NMDA antagonist) decreased responding in WSR2
      mice at doses that did not affect responding in WSP2 mice. Although a second non
      competitive NMDA antagonist, dizocilpine, produced line differences in the same
      direction as did PCP, these differences were not statistically significant. In
      contrast, NMDA produced nearly equipotent dose-dependent response rate decreases
      in both lines. Combined with the results of previous in vitro studies which
      showed that the number of NMDA receptors in the hippocampi of WSR2 and WSP2 mice
      differ, the results of the present study suggest that the interaction of EtOH
      with NMDA receptors may contribute to differences in the acute effects of ethanol
      on schedule-controlled behavior in WSP2 and WSR2 mice.

PMID- 11224178
TI  - Discriminative stimulus effects of NMDA in pigeons and monkeys.
AB  - White Carneaux pigeons (Columbo livia) and rhesus monkeys (Macaca mulatta) were
      trained to discriminate NMDA from saline in a two-response operant procedure.
      Both species dose dependently generalized NMDA to the training stimulus, although
      training was difficult and stimulus control was difficult to maintain. The
      competitive antagonist CGS 19755 (0.32 and 1.0mg/kg) blocked the discriminative
      stimulus produced by the training dose of NMDA in pigeons and monkeys. The same
      doses of CGS 19755 produced rightward, but not dose-dependent, shifts in the NMDA
      dose-response function in pigeons The non-competitive NMDA antagonist PCP was
      unable to block the discriminative stimulus produced by the training dose of NMDA
      in pigeons. Kainate and AMPA, as well as morphine, pentobarbital and d
      amphetamine, engendered >/= 90% NMDA-appropriate responding in at least 50% of
      pigeons tested. The finding that compounds form several different classes
      generalize to the training dose of NMDA suggests that the present discrimination
      lacks pharmacological selectivity. This discrimination may not serve efficiently
      as a procedure in which to examine NMDA agonist and/or antagonist activity.

PMID- 11224179
TI  - Tolerance to the discriminative stimulus effects of midazolam: evidence for
      environmental modification and dose fading.
AB  - The ability of behavioral variables to modify the development of tolerance to the
      discriminative stimulus effects of midazolam was evaluated. Rats were trained to
      discriminate 0.32mg/kg s.c. or 1.0mg/kg i.p. midazolam from no-drug, under a two
      lever procedure, in daily experimental sessions consisting of multiple discrete
      20-min trials: 15-min time-out, followed by 5-min under a fixed-ratio 15 schedule
      of food pellet delivery. Generalization testing was accomplished by administering
      progressively increasing doses of midazolam before each time-out period. During
      the chronic phases, twice daily injections of 10mg/kg midazolam or saline were
      given while discrimination training was either suspended or continued;
      generalization gradients for midazolam were determined weekly for 4 weeks.
      Chronic saline given when training was continued or suspended produced slight
      fluctuations in the midazolam minimal discriminable dose (MDD) (the first dose of
      midazolam in an individual generalization gradient to produce >/=90% drug-lever
      responding). Tolerance developed to the discriminative stimulus effects of
      midazolam when chronic midazolam was given while training was suspended: at Week
      4, chronic midazolam produced 3-to 57-fold rightward shifts in the midazolam
      generalization gradient. In contrast, continued training during chronic midazolam
      produced no tolerance to the discriminative stimulus effects of midazolam: at
      Week 4 of chronic midazolam the MDD of midazolam was not different from pre
      chronic and not different from either saline condition. The effects of chronic
      midazolam on stimulus effects and response rates were differentiated: despite
      tolerance to the stimulus effects of midazolam, there were no consistent changes
      in response rates during chronic midazolam administration.

PMID- 11224180
TI  - Pharmacological characterization of the discriminative stimulus properties of the
      dopamine D1 agonist, SKF 81297.
AB  - A range of selective dopamine D1 and D2 receptor agonists and antagonists was
      used to characterize to the discriminative stimuli produced by d-amphetamine
      (0.5mg/kg) and the D1 agonists SKF 81297 (0.1mg/kg). In rats trained to
      discriminate d-amphetamine (0.5mg/kg) from saline, d-amphetamine produced a dose
      related increase in per cent drug lever responding, and SKF 81297 did not show
      any d-amphetamine-like discriminative stimulus effects; neither did SKF 81297
      potentiate nor antagonize the d-amphetamine discriminative stimulus. In rats
      trained to discriminate SKF 81297 (0.1mg/kg) from saline, SKF 81297 produced a
      dose-related increase in per cent drug lever responding, and SKF 38393 and SKF
      83565 elicited full SKF 81297-like effects despite the fact that these compounds
      have widely differing efficacies for stimulating adenylate cyclase. SKF 81297 had
      a 25-fold greater potency than SKF 38393 in this assay. The D2 agonists, PHNO and
      ropinirole, did not display any SKF 81297-like discriminative stimulus effects.
      The SKF 81297 discriminative stimulus was completely blocked by the D1 antagonist
      SCH 23390 but was not blocked by the D2 antagonist BRL 34778.

PMID- 11224181
TI  - Practice-augmented tolerance to triazolam: evidence from an analysis of operant
      response durations and interresponse times.
AB  - In order to investigate contingent tolerance to triazolam (TZ), 16 rats were
      trained with a water reinforcer to respond under a multiple fixed ratio 30 (FR
      30)-differential reinforcement of low rate 20-s (DRL 20) schedule, during daily
      20-min sessions. FR 30 and DRL 20 performances were assessed with measures of
      response rate, response duration, interresponse times, and reinforcers delivered.
      In addition, operant responses for each schedule component were divided into fast
      and slow subclasses, based on interresponse times less than 1s and greater than
      1s. Initial dose-effect functions for these behavioural measures were obtained
      for TZ (0.05-0.5mg/kg). After a 30-day chronic TZ (0.5mg/kg) exposure period,
      during which half of the rats were gavaged pre-session (PRE) and the other half
      were gavaged post-session (POST), dose-effect functions were redetermined with a
      wider dose range (0.05-3.0mg/kg). The redetermined dose-effect functions for FR
      rate indicated that both PRE and POST groups developed resistance to the rate
      suppressing effects of TZ. In addition, the PRE group displayed more tolerance
      than the POST group on some, but not all, measures, especially at doses higher
      than 0.5mg/kg. The greater tolerance in the PRE group was observed for number of
      reinforcers in the DRL 20 component, for response duration for the slow subclass
      of responses in both FR 30 and DRL 20 components, and for the fast subclass of
      responses in the DRL 20 component. Moreover, in the PRE group, tolerance occurred
      to the response duration measure even though the chronic dose of 0.5mg/kg had
      little effect on this measure. These results demonstrate the value of
      microanalytic methods in addressing the problem of contingent tolerance. In
      addition, the data suggest that extensive experience of response execution under
      the influence of a drug can have an "inoculating effect" against the higher doses
      of the drug even in the absence of large disruptions in behaviour during the
      drugged practice itself.

PMID- 11224182
TI  - Shock avoidance but not DRL history reverses the effects of cocaine on punished
      behavior of squirrel monkeys.
AB  - A history of responding maintained by a shock-avoidance procedure can alter the
      effect of psychomotor stimulant drugs on punished responding. This study was
      designed to evaluate whether another type of historical intervention could also
      alter the effects of cocaine on punished responding and, as a result, clarify
      certain variables contributing to this effect. Lever pressing of four squirrel
      monkeys was suppressed by a punishment procedure consisting of a fixed-interval 5
      min schedule of food presentation in which every 30th response also produced a
      200-ms 5-mA electric shock. Cocaine (0.03-1.0mg/kg) had no effect on or reduced
      punished responding. Conditions were then changed and responding was maintained
      for several sessions by a differential reinforcement of low rate (DRL) schedule
      in which food was delivered only when one response followed another by at least
      25s. The punishment schedule was then reinstated and the effects of cocaine
      redetermined; the dose-response curve was similar to that initially obtained. The
      monkeys then responded on a shock-avoidance schedule in which each response
      postponed the next scheduled shock for 25s; shocks occurred every 5s in the
      absence of responding. Subsequently, the shock-avoidance schedule was replaced by
      the punishment schedule and the effects of cocaine were redetermined. In contrast
      to the initial determination of the effects of cocaine on punished responding,
      and the effects obtained following training on the DRL schedule, cocaine then
      produced response rate increases or no change in rate at several doses that
      formerly reduced responding. These results demonstrate that the rate-decreasing
      effects of cocaine on punished responding may be reversed by a history of
      responding on a shock-avoidance schedule and also indicate that a history of
      responding on a DRL schedule is not sufficient to reverse the effects of cocaine.
      These data suggest that a history of responding under schedules, such as the DRL,
      that engender responding that is typically increased by psychomotor stimulant
      drugs, is not sufficient to reverse the effects of these drugs on punished
      responding. The reversal of the effects of cocaine on punished responding
      resulting from a history of avoidance responding appears to be attributable to
      factors other than the rate-increasing effect of cocaine on responding maintained
      by avoidance.

PMID- 11224183
TI  - Effects of smoked marijuana on heart rate, drug ratings and task performance by
      humans.
AB  - Six subjects, reporting marijuana use between two and 30 times per month,
      participated in studies of the acute effects of smoked marijuana (0.0%, 2.0% and
      3.5% Delta(9)-THC, w/w) on heart rate, ratings of drug effect and task
      performance. Marijuana was administered using a uniform-puffing procedure with
      monetary contingencies associated with puff and breathhold duration. In general,
      heart rate and ratings, of "High" and dose "Potency" were increased by marijuana,
      and performance on some tasks was altered by drug administration. The relative
      sensitivity of the measures varied across subjects, and no single measure, such
      as heart rate or verbal rating of drug effect, could be used to predict the
      behavioral effects of marijuana. Marijuana puff durations were decreased at the
      highest dose, but dose-related changes in heart rate and task performance
      indicated that the change in smoking topography did not result in complete
      compensation for increased cannabinoid concentrations in marijuana smoke.

PMID- 11224184
TI  - Chronic nicotinic stimulation and blockade effects on working memory.
AB  - Acute and chronic nicotine treatment has been found to improve learning and
      memory function in a variety of tasks. In several studies we have found that
      chronic nicotine infusion improves working memory performance. Replicating these
      results, the current study showed that chronic nicotine treatment (12mg/kg/day)
      significantly improved working memory performance in the radial-arm maze. The
      nicotine effect did not diminish during the 2 weeks following withdrawal. The
      nicotine-induced improvement was eliminated when the nicotinic antagonist
      mecamylamine (3mg/kg/day) was given concurrently, suggesting that the nicotine
      effect was mediated via actions on the nicotinic receptor. Surprisingly, when
      this chronic dose of mecamylamine was given alone, it caused a transient
      improvement in choice accuracy during the first week of administration. This
      improvement subsequently became attenuated and was not evident at all by the
      third and fourth weeks of administration.

PMID- 11224185
TI  - Haloperidol potentiation of latent inhibition in rats: evidence for a critical
      role at conditioning rather than pre-exposure.
AB  - Latent inhibition (LI) reflects a cognitive process whereby repeated pre-exposure
      of a to-be-conditioned stimulus impairs subsequent conditioning. Since it is
      believed to reflect the ability of an organism to screen out irrelevant stimuli,
      disrupted LI has been suggested as a model for a cognitive deficit in
      schizophrenia. Animal studies have previously shown that indirect dopamine (DA)
      agonists can disrupt LI, an effect which is reversed by neuroleptics. Conversely,
      neuroleptics given alone potentiate LI. In this study, using pre-exposure to a
      tone stimulus which is subsequently paired with mild footshock, we have
      demonstrated that haloperidol given before conditioning only is equally as
      effective as haloperidol given twice, before pre-exposure and conditioning, in
      potentiating LI after 10 pre-exposures. This supports our earlier results with
      nicotine, pointing to conditioning as the critical time for the action of
      dopaminergic manipulations on LI. The implications for the use of potentiated LI
      as a screening test for neuroleptic action are discussed.

PMID- 11224186
TI  - Factors influencing the reinforcing and subjective effects of d-amphetamine in
      humans.
AB  - The reinforcing and subjective effects of oral d-amphetamine (AMP) were studied
      in a group of non-drug abusing adults (16 males, 13 females). A discrete-trial
      choice procedure was used to assess the reinforcing effects of a single dose of
      AMP (range 7.5-20mg across subjects). A number of factors (gender, current and
      past drug use, personality, motor activity, and baseline mood state and
      psychophysiological and sensory indices of arousal) were examined in an attempt
      to explain both within- and between-subject variability in response to AMP. Of
      the 29 subjects, 11 chose AMP on either two or three out of a possible three
      occasions. Cigarette smokers reported stronger aversive responses to AMP and
      chose the drug significantly less often than non-smokers. Subjects with a history
      of non-medical stimulant use reported less subjective response to AMP than
      subjects without such history. Within-subject variability in AMP choice was
      related to variability in subjective response to the drug across choice trials,
      as well as to variability in baseline mood: AMP was more likely to be chosen when
      subjects were more aroused and in a more positive mood at the time of the choice.
      These results provide new information regarding factors that may be relevant in
      determining individual differences in vulnerability to abuse of psychomotor
      stimulants.

PMID- 11224187
TI  - Differential tolerance to the behavioral effects of chronic pimozide and
      clozapine on multiple random interval responding in rats.
AB  - The behavioral effects of 10 days of chronic administration of the typical
      neuroleptic, pimozide, and the atypical neuroleptic, clozapine, were compared on
      a schedule of multiple random interval responding for food reinforcement and on
      photocell activity in rats. The low doses of both neuroleptics (0.125mg/kg
      pimozide, 1.25mg/kg clozapine) had little effect on any of the dependent
      variables measured. The high doses (1.0mg/kg pimozide, 10.0mg/kg clozapine)
      significantly disrupted response rates and reinforcement rates and significantly
      increased response duration when the drugs were first administered. Chronic
      administration, however, resulted in different profiles for the two drugs. While
      tolerance developed to the disruptive effects of clozapine, tolerance did not
      develop to the disruptive effects of pimozide and, on some dependent measures, an
      increased sensitivity developed. No tolerance developed to the disruptive effects
      of either drug on photocell activity. The effects of the drugs depended on the
      reinforcement density of the operant schedule.

PMID- 11224188
TI  - Overshadowing of nicotine discrimination in rats: a model for behavioural
      mechanisms of drug interactions?
AB  - Overshadowing can play an important role in conditioning with compound
      exteroceptive stimuli. Drug discrimination experiments have been carried out to
      examine overshadowing when mixtures of drugs serve as compound interoceptive
      stimuli. Three groups of rats were trained in a two-bar operant procedure with a
      tandem schedule of food reinforcement (n = 8). All rats were trained to
      discriminate (-)-nicotine (0.32mg/kg s.c.) from saline, but in two groups of
      animals midazolam (0.1 or 0.2mg/kg s.c.) was co-administered with the nicotine to
      generate a compound stimulus. Dose-response curves were determined with nicotine
      and midazolam in each group. In rats trained with nicotine alone, there was a
      steep dose-response curve for the discriminative stimulus effect of nicotine. The
      presence of the smaller dose of midazolam in the training stimulus clearly
      attenuated, and the larger dose prevented, the appearance of the discriminative
      effect of nicotine, whereas there was a concomitant increase in the
      discriminative response to midazolam. These results suggest that midazolam
      overshadowed the response to nicotine in a dose-related manner. In rats trained
      with nicotine alone, the same doses of midazolam had no effect on the
      discriminative response established to the nicotine stimulus, indicating the
      absence of pharmacological antagonism. The results illustrate how conditioning
      factors may provide a behavioural mechanism for interactions between abused
      drugs.

PMID- 11224189
TI  - Buspirone and lorazepam abuse liability in humans: behavioral effects, subjective
      effects and choice.
AB  - This study compared behavioral and subjective effects of two anxiolytics, the
      benzodiazepine lorazepam and the azaspirodecanedione buspirone, in healthy male
      volunteers with histories of sedative drug abuse. Placebo, lorazepam (1, 2, 4,
      8mg/70kg) and buspirone (15, 30, 60, 120mg/70kg) were administered p.o. in a
      mixed sequence in a double-blind, cross-over design. Lorazepam, but not
      buspirone, decreased psychomotor/cognitive performance. Both drugs produced
      similar increases in ratings of drug strength, however the onset and offset times
      for lorazepam were later than for buspirone. Lorazepam increased ratings of
      liking in contrast to buspirone which produced negative mood-related subjective
      effects (e.g. increases in ratings of disliking, bad/unpleasant effects, and
      tension-anxiety). Lorazepam was categorized by subjects as producing effects
      similar to barbiturates or benzodiazepines in contrast to buspirone which was
      not. When subjects were given a choice between self-administering an intermediate
      dose of lorazepam (4mg/70kg) or buspirone (60mg/70kg), which produced similar
      ratings of drug strength, eight out of nine subjects chose lorazepam. This study
      provides the clearest human experimental evidence to date that the abuse
      liability of buspirone is lower than that of a prototypic benzodiazepine, even at
      supratherapeutic doses.

PMID- 11224190
TI  - Social isolation attenuates rat forebrain 5-HT release induced by KCI stimulation
      and exposure to a novel environment.
AB  - The technique of microdialysis was employed to investigate in vivo 5
      hydroxytryptamine (5-HT) release in isolation-reared rats compared with socially
      reared rats. Two methods were employed to stimulate 5-HT release: local KCI
      injection into the frontal cortex of chloral hydrate anaesthetized rats, and the
      exposure of freely moving rats to a novel environment (the elevated x-maze).
      Microdialysis probes were implanted into the frontal cortex in the case of KCI
      stimulation and the ventral hippocampus in the case of exposure to the novel
      environment, and perfused with artificial CSF (1ul/min). Dialysis samples were
      collected every 20min and analysed for 5-HT and 5-hydroxyindole acetic acid (5
      HIAA) by HPLC with electrochemical detection. Both KCI injection (1ul, 100mM) and
      a 20min period on the elevated x-maze produced a significant increase in
      extracellular 5-HT in the socially reared rats. Neither the increase in
      extracellular 5-HT induced by KCI nor the increase on exposure to the elevated x
      maze were observed in the isolation-reared rats. Dialysate 5-HIAA was not
      affected in socially reared or isolation-reared rats, in either protocol. These
      results suggest that isolation-reared rats have a reduced presynaptic neuronal
      function to release 5-HT.

PMID- 11224191
TI  - Pharmacological specificity of the caffeine discriminative stimulus in humans:
      effects of theophylline, methylphenidate and buspirone.
AB  - The present study examined further the pharmacological specificity of the
      methylxanthine CNS stimulant caffeine as a discriminative stimulus in humans.
      Nine normal healthy volunteers (ages 19-39) were trained to discriminate between
      caffeine (320mg/70kg, p.o.) and placebo, using monetary reinforcement of correct
      letter code identification. After four training sessions, subjects were tested
      with the training conditions until they were >80% correct on four consecutive
      sessions. Then dose-effect curves were determined for caffeine (56-320mg/70kg),
      theophylline (56-320mg/70kg), methylphenidate (10-56mg/70kg), and buspirone (1
      32mg/70kg). Seven of nine subjects met the discrimination criterion within four
      to nine sessions. During dose-effect curve determinations, caffeine and
      methylphenidate each produced dose-related increases in caffeine-appropriate
      responding. Theophylline produced caffeine-appropriate responding that was not
      dose related in a consistent manner across subjects, occasioning an average of
      50% caffeine-appropriate responding at most doses tested. Buspirone produced
      predominantly placebo-appropriate responding. Caffeine-appropriate responding
      tended to be directly related to ARCI LSD scores, self-reported "bad" effects,
      "high", and stimulant-bad effects and inversely related to ARCI PCAG scores and
      sedative ratings. These results agree with non-human data and suggest that the
      caffeine discriminative stimulus has pharmacological specificity, in that
      caffeine-appropriate responding generalizes to other stimulants such as
      theophylline or methylphenidate, but not to non-stimulant compounds such as
      buspirone.

PMID- 11224192
TI  - Actions of ritanserin, a 5-HT(2/1C) antagonist, in benzodiazepine-dependent rats.
AB  - The effects of ritanserin on spontaneous benzodiazepine (BZ) withdrawal-induced
      weight loss, anorexia and hypodipsia were studied. Groups of female rats
      initially received i.p. injections b.i.d. (11.00 and 17.00h) of either saline or
      chlordiazepoxide (CDP). CDP doses increased by 2mg/kg/day from 10mg/kg to a final
      does of 30mg/kg. Treatment was maintained for 26 days. Over the next 6 days
      animals were either treated b.i.d. with vehicle, CDP, or ritanserin at one of
      three doses (0.16,0.63 and 2.5mg/kg). In CDP-pretreated animals subsequently
      treated with vehicle, significant weight loss, anorexia and hypodipsia were seen,
      relative to controls. In saline-pretreated animals ritanserin had no effect on
      body weight. However, CDP withdrawal-induced weight loss was actually exacerbated
      by ritanserin, in a dose-related fashion. Thus, ritanserin potentiated withdrawal
      induced weight loss, by a process which did not involve functional (additive)
      effects of withdrawal and ritanserin treatment. Ritanserin stimulated food intake
      in saline-pretreated animals. Despite this effect it failed to alleviate CDP
      withdrawal-induced anorexia. However, in contrast to the weight loss index, no
      evidence was obtained for potentiation of withdrawal-induced anorexia. In saline
      pretreated animals ritanserin had no effect on water intake, nor did it alleviate
      or potentiate CDP withdrawal-hypodipsia. Thus the effects of ritanserin on
      somatic BZ withdrawal signs depended upon the specific sign studied, different
      signs showing potentiation or no effect. However, for none of the signs studied
      was there any evidence that ritanserin alleviated the effect of CDP withdrawal. 5
      HT(2/1C) antagonists may therefore be of limited value in the treatment of
      somatic aspects of the BZ withdrawal syndrome. They may even exacerbate some BZ
      withdrawal signs, although a full characterization of the effects of such drugs
      on BZ withdrawal requires that a number of other different withdrawal signs and
      symptoms should be studied, since it seems likely that different BZ withdrawal
      signs involve different underlying mechanisms.

PMID- 11224193
TI  - Effects of phencyclidine and dizocilpine on NMDA-, kainate-, and water
      deprivation-induced drinking in pigeons.
AB  - The excitatory amino acid (EAA) agonists, N-methyl-D-aspartate (NMDA) and
      kainate, elicit a copious drinking response in pigeons. NMDA-induced drinking, as
      compared with kainate- and water deprivation-induced drinking, is selectively
      antagonized by the competitive, NMDA receptor antagonist CGS 19755, and appears
      to be mediated by NMDA receptors located in brain. There have been several
      studies which have reported differences between competitive and non-competitive
      (PCP-like) NMDA antagonists in blocking various behavioral effects of NMDA, such
      as discriminative stimulus effects. The present studies examined the effects of
      the non-competitive antagonists, phencyclidine (PCP) and dizocilpine, on drinking
      elicited by NMDA, kainate, and water deprivation. PCP and dizocilpine were
      effective antagonists of NMDA-induced drinking, resulting in surmountable shifts
      to the right in agonist dose-response functions. These compounds had little
      effect on drinking evoked by either kainate or water deprivation. These results
      support the notion that the dipsogenic effects of NMDA are mediated by NMDA-type
      receptors, and also provide important information as to the characteristics of
      non-competitive NMDA antagonists. EAA-induced drinking provides a useful tool for
      the examination of the behavioral pharmacology of EAA agonists and antagonists.

PMID- 11224194
TI  - Interactions of buspirone or gepirone with nicotine on schedule-controlled
      behavior of pigeons.
AB  - The primary purpose of the present study was to examine the interaction of
      buspirone with nicotine in pigeons responding under a fixed-ratio 30 schedule of
      food presentation. The hypothesis was that the dopamine D2 receptor antagonist
      activity of buspirone would attenuate the rate-decreasing effects of nicotine.
      When administered alone, buspirone (0.3-10mg/kg) and (-)-nicotine (0.1-3.0mg/kg)
      decreased response rates in a dose-related manner, with ED(50) values (+/-95%
      C.L.) of 3.0 (1.7-5.1) mg/kg and 1.0 (0.7-1.5) mg/kg, respectively. Low doses of
      buspirone (0.3-1.0mg/kg) did not significantly shift the nicotine dose-response
      function, while doses of buspirone (3.0-10mg/kg) that produced rate-decreasing
      effects shifted the nicotine dose-response function to the left. There was no
      significant statistical interaction between buspirone and nicotine indicating
      that the shifts in the nicotine dose-response function were parallel. The
      buspirone analog gepirone (0.3-10mg/kg), which like buspirone is a serotonin (5
      HT(1A)) agonist, but unlike buspirone is relatively devoid of D2 antagonist
      activity, was also tested in combination with nicotine. Gepirone was less potent
      in decreasing response rates compared with buspirone, with an ED(56) value of 4.5
      (3.1-6.7) mg/kg. Rate-decreasing doses of gepirone (3.0-10mg/kg) in combination
      with nicotine resulted in parallel shifts to the left of the nicotine dose
      response function. There was no statistically significant difference between the
      effects of buspirone and those of gepirone on the nicotine dose-response
      function. Isobolograms indicated that the pharmacological interactions between
      buspirone or gepirone and nicotine were not different from additivity. These
      results suggest that the combined effects of buspirone and nicotine on schedule
      controlled behavior are independent of antagonism at D2 receptors.

PMID- 11224195
TI  - Effect of serotonergic drugs on footshock-induced ultrasonic vocalization in
      adult male rats.
AB  - Modulation of ultrasonic vocalization (20-30kHz) emitted by adult rats under
      stressful conditions such as unavoidable foot-shock has been evaluated as a model
      of anxiety. The effects of 5-HT(1A) receptor agonists with different intrinsic
      activities and the role of other 5-HT(1) receptor subtypes, and of 5-HT(2) and 5
      HT(3) receptors, in mediation of ultrasonic vocalization were studied, as were
      the effects of increasing serotonergic activity by administration of the 5-HT
      releaser fenfluramine or the 5-HT precursor 1-5 HTP. The time spent vocalizing 1
      6min after four increascapable (1.0mA) footshocks was recorded. Drugs with
      affinity for 5-HT(1A) receptors (i.e. 8-OHDPAT, flesinoxan, ipsapirone,
      buspirone, gepirone, NAN-190) abolished the vocalization irrespective of their
      efficacy. The mixed 5-HT(1) receptor and beta-adrenoceptor antagonists (-)
      alprenolol and pindolol inhibited foot-shock-induced ultrasonic vocalization,
      whereas (-) penbutolol was ineffective. The beta(1)-adrenoceptor antagonist
      metoprolol and the beta(2)-adrenoceptor antagonist ICI 118.551 were without
      effect. This suggests that (-)-alprenolol and pindolol act as partial 5-HT(1)
      agonists in the test model. The non-selective 5-HT(1) receptor agonists
      eltoprazine, m-CPP and 5-MeODMT and the 5-HT(2) receptor agonists DO1 and d-LSD
      also abolished the vocalization, whereas the 5-HT(2) receptor antagonist
      ritanserin and the 5-HT(3) receptor antagonists ondansetron, ICS 205-930 and
      zacopride were without effect. (-)-Penbutolol reversed 8-OHDPAT-induced
      inhibition. Ritanserin reversed DOI-induced inhibition of ultrasonic
      vocalization, but not 8-OHDPAT-induced inhibition. This suggests that there is no
      functional interaction between 5-HT(1A) and 5-HT(2) receptors in this model.
      Fenfluramine and 1-5-HTP dose-dependently inhibited footshock-induced ultrasonic
      vocalization. These findings indicate that the effect most likely is mediated by
      postsynaptic 5-HT receptors, although contribution by presynaptic 5-HT receptors
      cannot be excluded. In conclusion, this study indicates that 5-HT(1A) receptors
      and 5-HT(2) receptors are involved in mediation of ultrasonic vocalization.

PMID- 11224196
TI  - Incomplete stimulus generalization from a mixture of d-amphetamine and morphine
      to different doses of the component drugs.
AB  - Pigeons were trained to discriminate a mixture of 1.8mg/kg morphine plus 1.0mg/kg
      d-amphetamine from saline, and then tested for generalization to various doses of
      d-amphetamine and morphine, alone and in combination. The birds discriminated the
      drug mixture from saline with more than 90% responding on the drug key. The
      training doses of morphine (1.8mg/kg) and d-amphetamine (1.0mg/kg), as well as
      lower doses of these drugs, did not reliably generate responding on the drug key
      when given in combination with saline. Higher doses of morphine and d-amphetamine
      did generate responding on the drug key, but not as reliably as the training dose
      combination. Combination of the training dose of morphine with doses of d
      amphetamine higher than those in the training dose combination resulted in
      somewhat less responding on the drug key than that seen with the training dose
      combination in one bird. These data and those from other experiments where
      animals were trained to discriminate drug mixtures can be characterized as the
      net effect of stimuli produced by the component drugs and interactions between
      the component drugs.

PMID- 11224197
TI  - Behavioural Sensitization.

PMID- 11224198
TI  - Tolerance and sensitization to the behavioral effects of drugs.
AB  - Tolerance and sensitization are relatively simple manifestations of learning and
      memory that refer to decreases and increases in the strength of a response to a
      stimulus induced by past experiences with the same or related stimuli. In the
      context of the study of drugs, tolerance refers to the decreased effectiveness of
      a given drug with repeated administration; sensitization to the increased
      effectiveness with repeated administration. Tolerance usually involves active
      adjustments or adaptation to the drug-induce disturbances of function, either
      within cells or within a neural system. In situations involving inter-neuronal
      events, these processes of adjustment may take the form of learned modifications
      that can be re-evoked on future occasions by events that co-occurred at the time
      of the original modifications. Sensitization, defined as the enhancement of a
      directly elicited drug effect, though adaptive, appears to represent facilitation
      within a system, making the effect easier to elicit on future occasions. Like
      tolerance, sensitization of a drug effect can become linked to the events that co
      occurred when the effect was originally elicited, making it possible for
      sensitization to come under selective event control. This paper is concerned with
      factors that affect whether tolerance and/or sensitization to the various effects
      of drugs will develop and be expressed, and with the variety and levels of
      mechanisms responsible for tolerance and sensitization under different conditions
      of exposure.

PMID- 11224199
TI  - Some future research directions: Commentary on Stewart and Badiani "Tolerance and
      sensitization to the behavioral effects of drugs"

PMID- 11224200
TI  - The pharmacology and neural circuitry of sensitization to psychostimulants.
AB  - Behavioral sensitization to amphetamine-like psychostimulants is manifest as a
      progressive increase in drug-induced anxiety and paranoia which can culminate in
      psychopathologies, such as paranoid psychosis and panic attacks. Sensitization
      may also mediate the facilitation of drug relapse in addicts by increasing the
      reinforcing value of acute drug administration. The primary animal model for
      psychostimulant-induced psychopathologies involves repeated, non-contingent
      administration of drug to rodents, which can produce a progressive and enduring
      augmentation in motor activity and increased susceptibility to drug self
      administration. Because of the mature literature implicating mesoaccumbens
      dopamine transmission in the acute motor and reinforcing effects of amphetamine
      like stimulants, investigation into the neural basis of behavioral sensitization
      has focused on this projection. Over the last decade, with a few exceptions, the
      neurochemical and molecular literature that has emerged from this effort is
      replete with inconsistencies. In contrast, the presence of behavioral
      sensitization is a highly replicable event. It is proposed that behavioral
      sensitization arises from an alteration in the neural circuitry that subserves
      the translation of motivationally relevant stimuli into adaptive motor responses.
      The mesoaccumbens dopamine projection is embedded in this circuit and an enduring
      change in dopamine transmission may alter the functional state of the circuit to
      produce behavioral sensitization. However, combinations of alterations in other
      connections within the circuit can also support behavioral sensitization. The
      specific changes in the circuit that promote behavioral sensitization are under
      the control of experimental parameters, such as the drug employed, dosage
      regimen, withdrawal period and the presence of conditioning cues. Thus, the
      profile of neurochemical alterations observed after exposure to repeated
      psychostimulants may vary depending upon the experimental protocol and strain of
      animals, even though all laboratories report the presence of behavioral
      sensitization.

PMID- 11224201
TI  - Searching for the hidden order in chaos. Commentary on Kalivas et al. "The
      pharmacology and neural circuitry of sensitization to psychostimulants"

PMID- 11224202
TI  - Psychomotor-stimulant sensitization: a unitary phenomenon?
AB  - Repeated intermittent treatment with psychomotor stimulants or opiates sensitizes
      animals to the locomotor activating effects of these drugs. Whereas such
      sensitization may have important implications for the understanding of addiction,
      mental illness, and the cellular basis of memory, its mechanisms remain only
      partially understood. Psychomotor-stimulant sensitization can result in
      relatively permanent changes in the response of the mesolimbic dopamine system to
      these agents and to a variety of stressors, but the process does not depend upon
      simple activation of dopaminergic neurons. Psychomotor sensitization can be
      produced by direct (apomorphine, bromocriptine) and indirect (amphetamine,
      cocaine) dopamine agonists that inhibit the firing of dopaminergic neurons and
      thus reduce impulse-dependent dopamine release. Moreover, some treatments that
      cause dopaminergic activation and dopamine (DA)-dependent locomotion fail to
      cause robust psychomotor sensitization. While nucleus accumbens injections of
      amphetamine cause DA release and enhanced locomotion, they do not sensitize the
      animals to subsequent systemic amphetamine. On the other hand, ventral tegmental
      injections of amphetamine inhibit the DA system and DA-dependent locomotion but
      none the less sensitize the animal to subsequent systemic amphetamine treatment.
      While some drugs (cocaine, amphetamine, morphine, heroin) cross-sensitize animals
      to each other, other drugs (bromocriptine, quinpirole) sensitize animals to
      themselves and each other but not to cocaine or heroin. While some cases of
      sensitization involve Pavlovian association of environmental cues with the drug
      state, others seem largely independent of such conditioning. Thus it appears that
      there is more than one phenomenon and more than one mechanism of psychomotor
      sensitization.

PMID- 11224203
TI  - Psychomotor stimulant sensitization: the corticotropin-releasing factor-steroid
      connection. Commentary on Wise and Leeb "Psychomotor-stimulant sensitization: a
      unitary phenomenon?"

PMID- 11224204
TI  - Controlling interindividual differences in the unconditioned response to
      amphetamine in the study of environment-dependent sensitization.
AB  - Two subgroups of rats selected on the basis of their emergence latency in a light
      dark box test were shown to exhibit significantly different unconditioned
      responses to d-amphetamine (AMPH, 1mg/kg). The rats presenting a low latency to
      emerge from the dark side (LL subgroup) responded more to AMPH than the rats
      presenting a high latency (HL subgroup). These two subgroups were compared for
      environment-dependent and environment-independent sensitization. The major
      findings were as follows: (a) when these two subgroups underwent a conditioning
      procedure to study environment-dependent sensitization, in which the paired
      groups received AMPH in Environment A (activity cages) and saline in Environment
      B (plastic housing cages), the unpaired groups received saline in A and AMPH in
      B, and the control groups received saline in both environments, only the LL
      subgroup showed conditioned activity and environment-dependent sensitization; (b)
      when LL and HL subgroups were submitted to a sensitization procedure designed to
      rule out any conditioning processes (environment-independent sensitization),
      there was no significant difference in the development and magnitude of
      sensitization although the amplitude of the response following each injection
      remained lower in the HL compared with the LL subgroup; (c) when unconditioned
      responses to AMPH for the two subgroups were equated by increasing the dose of
      AMPH for the HL rats (1.25mg/kg), there was no longer a significant difference
      between the two subgroups with respect to conditioned activity and environment
      dependent sensitization; (d) in the LL subgroup, an extinction procedure (in
      which all animals received vehicle in both environments) that completely
      abolished the conditioned activity in the paired group, suppressed the difference
      between paired and unpaired groups during the test for environment-dependent
      sensitization, by reducing the response of the former. Overall, these results
      provide two major contributions: first, they show that interindividual
      differences in the unconditioned response to AMPH influence the outcome of the
      study of environment-dependent sensitization; second, when these differences are
      controlled, they suggest that environment-dependent sensitization appears to be
      the result of the addition between conditioned activity and environment
      independent effects of AMPH.

PMID- 11224205
TI  - Strain-dependent behavioural sensitization to amphetamine: role of environmental
      influences.
AB  - Repeated daily pairings of 1mg/kg of amphetamine and test environment induced a
      large, significant increase of locomotion in mice of the C57BL/6 strain, while a
      slight, non-significant increase was observed in mice of the DBA/2 strain.
      Neither C57BL/6 nor DBA/2 mice showed behavioral sensitization to amphetamine in
      the test cages when the drug was repeatedly administered in their home cage.
      Moreover, C57BL/6 but not DBA/2 mice showed conditioned hyperactivity.
      Subsequently six daily pairings of saline and test cage produced a slight, non
      significant reduction of the hyperactive response shown by C57BL/6 mice,
      accompanied by a further increase in the behavioural effect of amphetamine.
      Finally, a similar, significant context-independent sensitization (unpaired vs
      control) was observed in mice of the two strains subjected to pairings of saline
      with the test cage; while context-dependent sensitization (paired vs unpaired)
      was observed only in C57BL/6 mice. Naive DBA/2 were less susceptible than C57BL/6
      mice to the behavioural effect of high doses of amphetamine. However, effects of
      the low dose of amphetamine used in this experiment did not show strain
      differences in naive mice. These results show that C57BL/6 are more susceptible
      than DBA/2 mice to context-dependent behavioural sensitization to amphetamine.
      Moreover, they suggest that neither conditioned hyperactivity nor context
      independent sensitization account for strain differences in environment-specific
      behavioural sensitization.

PMID- 11224206
TI  - The role of D1 and D2 dopamine receptors in the acquisition and expression of
      cocaine-induced conditioned increases in locomotor behavior.
AB  - Certain motoric effects of cocaine increase in intensity with repetitive
      administration. Conditioned drug effects are among primary determinants of such
      sensitization. The purpose of these experiments was to evaluate the role of D1
      and D2 dopamine (DA) receptor mechanisms in the acquisition and expression of
      cocaine conditioning. On Day 1, rats were injected with cocaine (40mg/kg) either
      before (PAIRED) or after (UNPAIRED) exposure to a locomotor activity chamber. On
      Day 2, all animals were injected with a low dose of cocaine (10mg/kg) prior to
      placement in the locomotor chambers. Conditioning on Day 2 was evidenced by
      significantly higher activity levels in the PAIRED group relative to the UNPAIRED
      or saline-treated groups. Pretreatment with D1 (SCH 23390) or D2 (raclopride,
      sulpiride, haloperidol) DA antagonists on Day 1 prevented the development of
      conditioning as assessed on Day 2, indicating that both receptor subtypes are
      involved in acquisition. However, pretreatment with raclopride or SCH 23390 on
      Day 2, prior to cocaine injections, did not eliminate the differences in behavior
      between the conditioned and non-conditioned groups. Neither D1 (SKF 82958, SKF
      38393) nor D2 (quinpirole) agonists administered alone were effective in
      establishing conditioning, while a combination of SKF 82958 and quinpirole was
      effective, suggesting that conditioning in this experimental paradigm requires
      the concurrent activation of both receptor subtypes. In the final study it was
      found that conditioned cocaine effects could be revealed only in the presence of
      quinpirole or apomorphine on Day 2. The D1 agonists (SKF 38393 and SKF 82958)
      were ineffective. This would suggest either that only quinpirole and apomorphine
      are effective in amplifying the conditioned effects of cocaine on Day 2 or that
      the cues produced by these drugs are more similar to those produced by cocaine
      than those produced by D1 agonists.

PMID- 11224207
TI  - "Priming" to dopamine agonist-induced contralateral turning as a model of non
      associative sensitization to the expression of the post-synaptic dopamine
      message.
AB  - In adult rats bearing unilateral 6-hydroxydopamine (6-OHDA) lesions of the
      ascending dopaminergic neurons, a single administration of a dopamine (DA)
      receptor agonist results in strong sensitization ("priming") of contralateral
      turning in response to D2 and particularly D1 receptor agonists. In order to
      investigate the role of distinct environmental cues associated with the effect of
      the agonist during exposure to the primer, rats bearing 15-day-old unilateral 6
      OHDA lesions were primed in their home cage with L-dopa or with saline. L-Dopa
      but not saline induced medium to low but steady contralateral turning. Three days
      later, challenge with the D1 agonist SKF 38393 in the home cage also resulted in
      contralateral turning in the rats previously primed with L-dopa, but not in those
      primed with saline. In a second experiment rats lesioned with 6-OHDA were primed
      in two different contexts (hemispheres versus cylinders) with a single
      administration of the D2/D3 agonist quinpirole (LY 171555: 0.2mg/kg s.c.) or
      saline. Three days later the rats were placed in hemispheres and tested for
      contraversive turning in response to saline or to SKF 38393. SKF 38393 elicited
      high rate contraversive turning independently of the environment where priming
      with quinpirole took place; on the other hand no conditioned contraversive
      turning was observed after saline. In a third experiment, the possibility of
      priming SKF 38393-induced turning by stimulation of nigral or striatal DA
      receptors was investigated. Rats lesioned unilaterally with 6-OHDA were locally
      infused on the lesioned side in the substantia nigra with SKF 38393 or in the
      striatum with quinpirole. Both these treatments elicited contralateral turning,
      the intranigral injection of SKF 38393 eliciting a stronger and longer lasting
      contraversive turning than intrastriatal quinpirole. Challenge with SKF 38393
      (3mg/kg s.c.) 3 days later induced contralateral turning only in rats previously
      primed with intrastriatal quinpirole. The results of these studies are consistent
      with the idea that "priming" is an example of non-associative sensitization
      induced by stimulation of denervated striatal DA receptors and expressed as an
      increased efficiency of post-synaptic dopaminergic transduction in the striatum.

PMID- 11224208
TI  - Environmental modulation of both locomotor response and locomotor sensitization
      to the dopamine agonist quinpirole.
AB  - The study tested whether differences in locomotor activation during chronic
      treatment result in differential behavioral sensitization induced by the D2/D3
      dopamine agonist quinpirole. One group of rats received repeated injections of
      quinpirole in their home cage and another group received this treatment in an
      alternate environment of similar size. In the home cage, quinpirole induced less
      locomotion than in the non-home environment. When tested in activity monitors at
      the end of chronic treatment, the home cage group showed less sensitized
      locomotion to quinpirole than the non-home cage rats. Thus, the extent of
      locomotor sensitization to quinpirole appears to be related to the amount of
      locomotion characteristic of the training environment. Such differential
      sensitization may reflect a modulation of the hierarchy of expression of
      quinpirole-enhanced hyperactivity via a non-associative process.

PMID- 11224209
TI  - Environmental and behavioral components of sensitization induced by the dopamine
      agonist quinpirole.
AB  - Chronic intermittent injection of quinpirole (0.5mg/kg) to rats in a large non
      standard open field (mirrored glass table without walls, 160 x 160cm and 60cm
      high) induces pronounced behavioral sensitization characterized by a 6-fold
      increase in locomotor distance and increased rigidity of travel along the same
      routes (path stereotype). Experiment 1 showed that equivalent treatment in the
      home cage induces much less sensitization of locomotor distance and no
      sensitization of path stereotypy, as evidenced by a test in the open field. In
      Experiment 2, transferring rats sensitized in one open field to a novel open
      field resulted in a 50% loss of sensitized locomotor distance and a virtual loss
      of sensitized path stereotypy. In Experiment 3, rotating the open field in
      relation to room cues did not affect sensitized responding, suggesting that the
      behavior is organized in relation to distal rather than local (open field) cues.
      Finally, an injection of saline in the sensitized environment failed to elicit
      conditioned locomotion (Experiment 4). These results are taken to indicate that
      the control of sensitization to quinpirole has components that are environment
      independent, behavior specific, and context dependent, each having a relatively
      different contribution and mechanism. It is suggested that under the experimental
      conditions of this study, the relative contributions to quinpirole sensitization
      were 50% for the context-dependent component, 30% for the behavior-specific
      component, and 20% for the environment-independent contribution. The mechanism
      for the context-dependent component may be related to development of path
      stereotypy and involve spatial learning.

PMID- 11224210
TI  - Dissociation of the effects of amphetamine and quinpirole on dopamine release in
      the nucleus accumbens following behavioural sensitization: an ex vivo
      voltammetric study.
AB  - Behavioural sensitization to the locomotor stimulant effect of (+)-amphetamine or
      quinpirole was induced in rats by intermittent drug administration. Once
      established, endogenous dopamine release (DA) was measured in slices containing
      nucleus accumbens using fast cyclic voltammetry. DA release induced by single
      pulse electrical stimulation did not differ between vehicle-, (+)-amphetamine-or
      quinpirole-treated groups. Multiple pulse stimulation resulted in enhanced DA
      release in quinpirole-sensitized rats and an attenuation of DA release in (+)
      amphetamine-sensitized rats. In the presence of sulpiride, DA release was
      increased, at low stimulation frequencies, in vehicle- and quinpirole-treated
      animals, but not in amphetamine-treated animals. The sensitivity of axon terminal
      D2 DA receptors was assessed in vitro by measuring the concentration of
      quinpirole required to inhibit single pulse release of DA by 50% (EC(50)).
      Quinpirole EC(50) was significantly increased in the quinpirole-treated animals
      and significantly attenuated in the (+)-amphetamine-treated animals. The results
      suggest that the increase in DA release following quinpirole may arise from the
      desensitization of release-regulating D2 autoreceptors in the nucleus accumbens.
      The sensitization of axon terminal D2 autoreceptors and the decrease in DA
      release following behavioural sensitization with (+)-amphetamine is difficult to
      reconcile with a unitary explanation of behavioural sensitization to both
      quinpirole and (+)-amphetamine. It is suggested that the effects following (+)
      amphetamine may be secondary to decreased axon traffic caused by DA displacement
      in the ventral tegmental area, and that the drugs examined in this study may
      induce behavioural sensitization by different mechanisms at different sites.

PMID- 11224211
TI  - Tolerance and sensitization to stimulant and depressant effects of nicotine in
      intracranial self-stimulation in the rat.
AB  - Nicotine is thought to be an important factor in addiction to tobacco but its
      psychopharmacological properties are still uncertain. In the present study, rats
      were trained to operate a pedal to obtain threshold-current, variable-interval
      hypothalmic stimulation. Response rates were printed out at 10min intervals to
      provide a continuous record of facilitatory or depressant effects by injected
      nicotine. Responding was enhanced in all rats but this depended on dose, time
      after injection, and previous exposure to the drug. In the first 10min after
      injection, responding by drug-naive rats was either unaffected (40-130mg/kg s.c.,
      as base) or strongly depressed (400ug/kg). This phase was followed by prolonged
      (>50min) dose-dependent facilitation. Higher doses (1.3mg/kg) caused prostration.
      Chronic exposure to nicotine (400ug/kg x 10 at 2-5 day intervals) reduced the
      initial depressant effect; it also augmented subsequent responding, but only in
      the early minutes after injection; the latter finding indicates that apparent
      sensitization to chronic nicotine may depend primarily on tolerance to its
      depressant effects, rather than on receptor upregulation. Stimulant and
      depressant effects of nicotine were prevented by pretreatment with the centrally
      acting antagonist, mecamylamine (2.0mg/kg s.c.), but not by the peripheral
      antagonist, hexamethonium (1.0mg/kg s.c.) or by the muscarinic receptor
      antagonist, hyoscine (scopolamine; 100-300ug/kg s.c.). Self-stimulation was
      unaffected by mecamylamine alone. Thus the inhibitory action of nicotine is
      unlikely to be due to depolarization block, peripheral activity or muscarinic
      activity. Its facilitatory and depressant effects appear to be narrowly time- and
      dose-specific, thus accounting for divergent findings in many studies.

PMID- 11224212
TI  - Behavioral sensitization to MK-801 (dizocilpine): neurochemical and
      electrophysiological correlates in the mesoaccumbens dopamine system.
AB  - MK-801, a non-competitive antagonist at the N-methyl-D-aspartate (NMDA) subtype
      of central glutamate receptor, stimulates locomotor activity in rats.
      Administration of MK-801 (0.25mg/kg, i.p.) on four consecutive days results in
      progressive sensitization of its locomotor stimulatory effects. Because of the
      importance of dopamine (DA) systems in locomotor sensitization to other
      stimulants (e.g. amphetamine and cocaine), we examined the possible role of DA
      transmission in MK-801 sensitization. The D1 antagonist SCH 23390 was used for
      these experiments because of the well-established ability of D1 antagonists to
      block both D1- and D2-mediated unconditioned behaviors. Acute behavioral effects
      of MK-801 were reduced by SCH 23390 only at doses that decreased basal activity,
      while the expression of MK-801 sensitization was attenuated by SCH 23390 in some
      experiments but never completely prevented. Co-administration of SCH 23390 with
      MK-801 on pretreatment days did not prevent the development of sensitization. In
      vivo microdialysis experiments compared the effect of MK-801 on extracellular DA
      levels in the nucleus accumbens (NAc) on Days 1 and 4 of repeated administration.
      On Day 1, MK-801 produced a modest elevation of DA levels. On Day 4, only 6/17
      rats in microdialysis experiments expressed sensitization; these rats, however,
      exhibited a more rapid rise in DA levels than Day 1 rats or non-sensitized Day 4
      rats. Electrophysiological studies revealed that repeated MK-801 administration
      resulted in supersensitivity of D1 receptors on NAc neurons. Thus, behavioral
      studies support the importance of non-dopaminergic mechanisms in MK-801
      sensitization, while neurochemical and electrophysiological studies suggest that
      MK-801 sensitization is accompanied by changes in DA transmission in the NAc
      similar to those observed in amphetamine- or cocaine-sensitized rats.

PMID- 11224213
TI  - Fixed-ratio size as a determinant of tolerance to cocaine: is relative or
      absolute size important?
AB  - Six studies, examining five drugs in three species, have demonstrated that
      tolerance development is impaired under relatively long fixed-ratio (FR)
      schedules compared with relatively short FR schedules. One such study
      demonstrated that substantial tolerance to the rate-reducing effects of cocaine
      in pigeons developed under the FR 5 and 25 components of a multiple schedule of
      food delivery, but little or no tolerance developed under the FR 125 component.
      The present study examined the acute and chronic effects of cocaine in three
      groups of pigeons. One group was exposed to a simple FR 5 schedule of food
      delivery, a second to a simple FR 125 schedule of food delivery, and a third to a
      simple FR 125 schedule that alternated across sessions with a multiple FR 125 FR
      250 schedule. When administered acutely, cocaine (1-10mg/kg) produced dose
      dependent rate decreases under all schedules. With chronic exposure to 5.56mg/kg
      cocaine, tolerance clearly developed under the FR 5 schedule. Evidence of
      tolerance under the FR 125 schedule was equivocal, but strongest when that
      schedule alternated with an FR 250 component under a multiple schedule
      arrangement. There was no consistent evidence of tolerance under the FR 250
      component. These results suggest that, although the development of tolerance
      under an FR schedule may be affected by exposure to a longer schedule, tolerance
      to cocaine does not develop readily under "long" FR schedules, regardless of the
      context in which they appear.

PMID- 11224214
TI  - Differential effects of ondansetron, haloperidol and clozapine on electrical self
      stimulation of the ventral tegmental area.
AB  - The effects of 5-HT(3), receptor blockade with ondansetron (0.025-0.2mg/kg) on
      intracranial self-stimulation of the ventral tegmental area were compared with
      effects of the typical antipsychotic drug haloperidol (0.01-0.3mg/kg) and the
      atypical antipsychotic drug clozapine (1.25-10mg/kg). Rats were trained to self
      stimulate using unipolar ventral tegmental electrodes (200um diameter) to deliver
      1s trains of 0.2ms cathodal pulses of constant current stimulation as a
      reinforcer. The animals were tested daily in frequency threshold tests. The
      frequency that maintained half maximal response rates (M50) and the maximal
      number of responses at a single frequency (RMAX) and the number of responses per
      session (TRESP) were used to measure drug effects. Ondansetron had no effects on
      the behavioural measures in this study. Haloperidol induced a significant
      increase in M50 at 0.3mg/kg without altering RMAX; TRESP was reduced by 0.1 and
      0.3mg/kg of this drug. Clozapine increased M50 at 5.0mg/kg; following 10.0mg/kg
      of clozapine responding was completely abolished and no M50 measure could be
      calculated. Clozapine reduced RMAX at 1.25, 5.0 and 10.0mg/kg; TRESP was
      decreased by 5.0 and 10.0mg/kg of clozapine. The present results indicate that
      ondansetron had no measurable effects under conditions in which haloperidol and
      clozapine increase reinforcement thresholds and decrease response rates
      maintained by ventral tegmental self-stimulation.

PMID- 11224215
TI  - Variable-ratio schedules of timeout from avoidance: effects of anxiolytic drugs.
AB  - Concurrent performances in rats were studied under conditions where responses on
      one lever postponed shock on an unsignaled avoidance schedule, and responses on
      another level produced periods of signaled timeout from avoidance on a variable
      ratio schedule. This procedure resulted in relatively high rates of responding on
      the timeout lever, and provided a baseline which permitted simultaneous
      evaluation of drug effects on two different types of negative reinforcement
      (shock postponement vs timeout). Chlordiazepoxide and ethanol selectively
      increased responding on the timeout lever at low doses, while higher doses
      decreased responding on both levers. Two 5-HT(1A) agonists, buspirone and 8-OH
      DPAT, had different effects. Buspirone decreased responding across all effective
      doses, but 8-OH-DPAT increased responding on both the timeout and avoidance
      levers, with greater increases noted in responding maintained by timeout. These
      results replicate and extend previous findings, and support the notion that
      traditional anxiolytic drugs like chlordiazepoxide and ethanol may increase the
      reinforcing properties of escape from an avoidance schedule. Differences between
      the behavioral effects of buspirone and 8-OH-DPAT may reflect differential
      activity at the 5-HT(1A) receptor or the dopaminergic properties of buspirone.

PMID- 11224216
TI  - Substance P effects on intraspecific aggressive behaviour of isolated male mice:
      an ethopharmacological analysis.
AB  - Adult male mice of the Swiss CD1 strain were used to evaluate the effects on
      isolation-induced aggressive behaviour of a single intravenous administration of
      substance P (SP; 0.25, 1.0 or 2.5mg/kg dose). All mice were injected 15min before
      testing (10min videotaped dyadic encounters with an isolated male untreated
      opponent). Control mice were injected with vehicle. All animals were tested again
      24h later in a drug-free state. SP treatment produced a decrease in offensive
      scores (Attacks and Rattling behaviour), a longer latency to the first Attack
      episode, and enhanced defensive displays. These effects were reversed 24h later.
      In no case did SP treatment affect locomotor activity levels or freezing
      behaviour. A role of SP in the regulation of murine aggressive response is
      strongly suggested through a direct action of the drug on the central nervous
      system and specifically on the hypothalamus.

PMID- 11224217
TI  - The effects of caffeine in the social interaction test and on exploration in
      rats: comparison with ethanol and clorazepate.
AB  - The effects of caffeine (20mg/kg) in the holeboard and social interaction tests
      were compared with those of ethanol (0.4g and dipotassium clorazepate (3mg/kg),
      following acute administration in one group of rats or after five daily
      injections in another group. The rats were put in pairs into an unfamiliar arena
      with high levels of illumination (n = 80), or tested individually in the
      holeboard (n = 80). Acute caffeine produced no effect on the time spent in social
      interaction, although it enhanced the number of social contacts, and both genital
      and total sniffing. Following five injections, caffeine also increased the time
      spent in social interaction. Acute clorazepate enhanced this time but this effect
      showed partial tolerance after five injections. Clorazepate also enhanced the
      number and duration of social contacts, increasing social grooming and genital
      sniffing, regardless of the duration of the treatment. Ethanol increased the time
      spent in social interaction following five injections, and increased social
      grooming. In the holeboard, stimulant effects were observed for caffeine and
      clorazepate, showing partial tolerance and without any effect on head dipping. In
      the social interaction test, only a stimulant effect for caffeine was obtained.
      The results of this study suggest that, under some circumstances, caffeine may
      enhance social interaction, in a manner similar to standard anxiolytics. Such an
      effect is potentiated by repeated administration.

PMID- 11224218
TI  - U-50, 488, saline and naltrexone discrimination in U-50, 488-treated pigeons.
AB  - Pigeons treated with 10.0mg/kg/day of U-50,488 discriminated among intramuscular
      (i.m.) injections of U-50,488 (10mg/kg), saline, and naltrexone (0.178mg/kg),
      while responding under a fixed-ratio 20 schedule of food presentation. Training
      compounds occasioned responding on the appropriate keys with pigeons responding
      >/=90% on the naltrexone key at doses larger than 0.032mg/kg of naltrexone,
      >/=90% on the U-50,488 key at doses larger than 3.2mg/kg of U-50,488, and >/=90%
      on the saline key after saline. Several opioid agonists and antagonists were
      studied for their discriminative stimulus effects. None of the compounds
      substituted completely (>/=90%) for either training compound in all pigeons (n =
      5); however, bremazocine substituted completely for U-50,488 in three out of five
      pigeons. Compounds with opioid antagonist actions under other conditions
      substituted for naltrexone in some subjects: levallorphan, two out of five;
      nalbuphine, one out of five; nalorphine, two out of five; and quadazocine, three
      out of four. Morphine did not substitute for naltrexone or U-50,488 in any of the
      subjects. When U-50,488 treatment was terminated and subjects were studied daily
      after injections of saline, responding occurred predominantly on the saline key;
      the absence of naltrexone key responding after termination of U-50,488 treatment
      suggests that this dosing regimen was not adequate for the development of
      dependence, or that the discriminative stimulus effects of abstinence-induced
      withdrawal were qualitatively different from the discriminative stimulus effects
      of naltrexone under these conditions.

PMID- 11224219
TI  - The attenuation of schedule-induced polydipsia by dopamine blockers is not an
      expression of extrapyramidal side effect liability.
AB  - The effects of scopolamine and diazepam on attenuation of schedule-induced
      polydipsia (SIP) produced by a dopamine D1 antagonist, SCH 23390, a dopamine D2
      antagonist, raclopride, and a mixed D1/D2 antagonist, cis(Z)-flupentixol, were
      examined in a chronic dose regime, followed by 7 days of withdrawal. Scopolamine
      potentiated the effect of SCH 23390, but did not alter the effects of raclopride
      of flupentixol. Diazepam reversed the effect of flupentixol, suppressed the
      reversal of the SCH 23390-treated group to control level after withdrawal, and
      was without effect of the raclopride-treated group. It is concluded that the
      suppression of SIP behaviour induced by the dopamine blockers is not due to the
      induction of extrapyramidal side effects. However, it cannot be excluded that the
      effects of SCH 23390 and flupentixol may be mediated through the motoric dopamine
      system, as they inhibited the initiation of drinking behaviour.

PMID- 11224220
TI  - Substitution by NMDA antagonists and other drugs in rats trained to discriminate
      ethanol.
AB  - It has been reported that, in animals trained to discriminate ethanol, stimulus
      control generalized to the non-competitive NMDA antagonists phencyclidine,
      ketamine and dizocilpine. In the present study, rats were trained to discriminate
      a dose of ethanol (1g/kg, i.p.) and substitution tests were carried out with
      phencyclidine, dizocilpine, CGS 19755, eliprodil, triazolam, chlordiazepoxide,
      abecarnil, alpidem and d-amphetamine. Phencyclidine and dizocilpine produce dose
      related substitution for ethanol as did the competitive NMDA antagonist, CGS
      19755, and the benzodiazepines, triazolam and chlordiazepoxide. Eliprodil, an
      NMDA antagonist acting through the polyamine modulatory site, neither substituted
      for ethanol nor modified the ethanol dose-response curve. d-Amphetamine, and the
      non-benzodiazepine anxiolytics, alpidem and abecarnil, did not substitute for
      ethanol. The results show that both NMDA antagonists and compounds acting through
      (GABA receptors (benzodiazepines) can substitute for ethanol, emphasizing that
      the ethanol cue may involve several mechanisms. As all the drugs substituting for
      ethanol, like ethanol itself, are known to produce ataxia and muscle relaxation,
      it is proposed that this property may be an important aspect of the ethanol cue.

PMID- 11224221
TI  - Failure of flumazenil to precipitate a withdrawal syndrome in cats chronically
      treated with the new anxioselective beta-carboline derivative abecarnil.
AB  - The effect of chronic administration of the novel anxiolytic beta-carboline
      derivative, abecarnil (isopropyl-6-benzyloxy-4-methoxymethyl-beta-carboline-3
      carboxylate), was examined and compared with the capability of diazepam to induce
      physical dependence in cats. The acute administration of the benzodiazepine
      receptor antagonist, flumazenil (20mg/kg i.p.), to cats treated for 2 weeks with
      diazepam (7mg/kg i.p., three times daily), induced a severe withdrawal syndrome
      characterized by the appearance of severe physical signs. Within minutes all cats
      displayed tremors, increased muscle tone, fear response, repeated vocalization
      and salivation. On the contrary, in all cats treated chronically (2 weeks) with
      abecarnil (7mg/kg i.p. three times daily) the challenge dose of flumazenil failed
      to precipitate a clear abstinence syndrome. In fact, a pupillary dilatation and a
      mild fear response were the only signs present 15-30min after flumazenil
      administration. This finding indicates that abecarnil, a new potential
      therapeutic agent for anxiety disorders and seizures, might have advantages over
      classical benzodiazepines with regard to development of physical dependence.

PMID- 11224222
TI  - Chronic nicotine ingestion improves radial arm maze performance in rats.
AB  - Effects of chronic nicotine treatment on spatial memory were studied in rats.
      After 3 weeks of administration of 2.5mg/kg/day in drinking water, the rats were
      submitted to a spatial learning task in an eight-arm radial maze, during which
      time the treatment was maintained. Chronic nicotine treatment improved daily
      spatial memory performance after the animals reached an asymptotic level.
      Nicotine-treated animals showed significantly better performance than control
      animals regarding the first error and the total correct path choices.

PMID- 11224223
TI  - Prenatal caffeine exposure modifies behavioural responses in mice.
AB  - Caffeine was given to pregnant mice subcutaneously at doses of 10 and 40mg/kg
      body weight, on the last four days of pregnancy. Subsequently, effects on the
      behaviour of their cross-fostered male offspring were studied using the "standard
      opponent" test. Significant decreases in threat, attack, displacement and number
      of fights, as well as an increase in latency to attack, were observed in the
      offspring exposed to the higher dose. Thus, excessive consumption of caffeine
      during pregnancy appears to have a lasting influence on the behaviour of
      offspring via a direct in utero action.

PMID- 11224224
TI  - Discrimination of agonist-antagonist mixtures: experiments with nicotine plus
      mecamylamine.
AB  - Discrimination of a mixture of an agonist plus an antagonist has been analysed by
      training rats to discriminate (-)-nicotine (0.32mg/kg s.c.) from saline; in
      different groups of rats (n = 8), nicotine was administered either alone or in
      combination with the non-competitive nicotine antagonist mecamylamine (0.1
      0.8mg/kg s.c.). Rats were trained in a two-bar operant conditioning procedure
      with a tandem schedule of food reinforcement. After 50 sessions, rats trained
      with nicotine alone had acquired the discrimination with an accuracy of about
      85%. In combination, mecamylamine blocked accuracy during acquisition in a dose
      related manner. In generalization tests, rats trained with nicotine alone yielded
      a typical dose-response curve for nicotine (ED(50) = 0.082mg/kg), without
      depression of response rate. In rats trained with nicotine plus 0.2mg/kg of
      mecamylamine, the ED(50) for the discriminative effect of nicotine was lowered
      (ED(50) = 0.036mg/kg), again without depression of response rate. In rats trained
      with nicotine plus 0.4-0.8mg/kg of mecamylamine, nicotine did not acquire
      stimulus control over behaviour (flat dose-response relationships), but in these
      animals, nicotine had a pronounced response rate-decreasing effect. These
      characteristics of discriminations based on nicotine plus mecamylamine differed
      substantially from those of previously described discriminations of nicotine plus
      midazolam, supporting the hypothesis that interactions between the latter drugs
      were based on a behavioural mechanism (overshadowing) rather than on interactions
      at the level of receptors.

PMID- 11224225
TI  - Acute behavioral and cardiac effects of alcohol and caffeine, alone and in
      combination, in humans.
AB  - The acute behavioral and cardiac effects of alcohol (0, 0.5 and 1.0g/kg) and
      caffeine (0,250 and 500mg/70kg), administered alone and in combination, were
      assessed in eight adult humans. Subjects received all possible combinations
      twice. Alcohol administered alone disrupted responding in the Digit-Symbol
      Substitution Test and the Repeated Acquisition and Performance Procedure,
      increased heart rate, decreased blood pressure, and increased subject ratings of
      drunkenness. Caffeine administered alone offset performance decrements that
      emerged across the test session on the Digit-Symbol Substitution Test performance
      and accuracy of responding in the Repeated Acquisition and Performance Procedure,
      but never actually enhanced performance and learning. Caffeine administered alone
      increased blood pressure and increased subjective ratings of drug strength. The
      most notable effect of the drug combination was that caffeine partially
      attenuated the disruptive behavioral effects of alcohol. Combining alcohol and
      caffeine generally offset the presser effects observed with the drugs
      administered alone. By contrast, alcohol-caffeine combinations did not
      significantly alter breath alcohol levels, heart rate or subject-rated drug
      effects, relative to the effects of the drugs alone. Across all measures except
      heart rate, these effects are qualitatively similar to those observed previously
      with cocaine and d-amphetamine in combination with alcohol, documenting a high
      degree of consistency in the behavioral pharmacology of alcohol-stimulant
      combinations in humans.

PMID- 11224226
TI  - An ethological analysis of the effects of chlordiazepoxide and bretazenil (Ro 16
      6028) in the murine elevated plus-maze.
AB  - The effects of chlordiazepoxide (2.5-15.0mg/kg), a full benzodiazepine receptor
      agonist, and bretazenil (5.0-30.0mg/kg), a partial benzodiazepine receptor
      agonist, were examined in the murine elevated plus-maze paradigm. Behaviours
      recorded comprised the traditional indices of anxiety as well as a number of
      ethologically derived measures. Results show that chlordiazepoxide (10-15mg/kg)
      and bretazenil (5-30mg/kg) not only decreased traditional indices of anxiety but
      also reduced risk assessment behaviours such as head-dipping and stretch attend
      postures from secure areas of the maze. Both compounds produced these effects
      without adversely affecting general activity levels. While traditional indices of
      anxiety did not clearly discriminate between the two compounds, some differences
      were apparent on the ethological measures. The dose-response curves for
      bretazenil were generally shallower than those for chlordiazepoxide, confirming
      its partial agonist profile. Together, these data support the view that
      benzodiazepine receptor partial agonists may have utility in the management of
      human anxiety disorders.

PMID- 11224227
TI  - Tolerance to the discriminative stimulus effects of Delta(9)
      tetrahydrocannabinol.
AB  - Although tolerance to a variety of behavioral and physiological effects of
      Delta(9)-tetrahydrocannabinol (Delta(9)-THC) has been demonstrated, previous
      studies have reported that tolerance to the discriminative stimulus effects of
      Delta(9)-THC does not develop when discrimination training is continued during
      repeated administration. The present study investigated development of tolerance
      to the discriminative stimulus effects of Delta(9)-THC under conditions of
      supplemental administration during suspended training. Rats, trained to
      discriminate Delta(9)-THC (3mg/kg) from vehicle in a two-lever drug
      discrimination procedure, under a fixed-ratio 10 schedule of food reinforcement,
      were tested with cumulative doses of Delta(9)-THC before and after repeated
      administration of vehicle and of high doses of Delta(9)-THC. Following suspended
      training with repeated vehicle injection, the Delta(9)-THC dose-effect curve for
      percentage of drug lever responding showed little change from the prevehicle
      curve. After supplemental administration of Delta(9)-THC, the degree of rightward
      shift in the post-THC dose-effect curve was 40-fold. Recovery to pre-THC levels
      of percentage of drug lever responding was observed during a second post-THC dose
      effect curve administered 23 days later. The large reversible shift in the dose
      effect curve following supplemental administration of Delta(9)-THC suggests that
      tolerance developed to the discriminative stimulus effects of Delta(9)-THC under
      suspended training conditions.

PMID- 11224228
TI  - Effects of pharmacological manipulations on "demand" for food by baboons.
AB  - In a study examining the effects of pharmacological manipulations on "demand" for
      food, responding of six adult male baboons (Papio c. anubis) was maintained under
      a fixed-ratio schedule of food reinforcement during daily 22h experimental
      sessions. Increasing the response requirement decreased daily food intake.
      Administration of anorectic drugs (amphetamine, fenfluramine, diethylpropion,
      phenmetrazine, phenylpropanolamine and mazindol) produced parallel dose-dependent
      downward shifts in responding at all response costs. In contrast, administration
      of the anxiolytic, diazepam, produced parallel dose-dependent upward shifts in
      responding at all response costs. Oral phencyclidine decreased intake during the
      first 8h of the session, but compensatory feeding later in the day eliminated
      this effect. Changes in pellet intake were fitted to a theoretical equation
      derived by Hursh et al. (1988) to describe changes in demand for a commodity.
      When responding increases as a result of increasing cost, demand is said to be
      inelastic, but when responding decreases as a result of increasing cost, demand
      is said to be elastic. Administration of anorectic drugs, while decreasing
      maximal intake at minimal cost, had no effect on the elasticity of demand for
      food. Similarly, diazepam increased maximal intake at minimal cost without
      affecting the elasticity of demand for food. The effect of anorectic drugs
      differs from the previously reported effects of caloric substitutes which
      increase the elasticity of demand for food. Thus, anorectic drugs do not function
      as caloric substitutes, in an economic sense, for food.

PMID- 11224229
TI  - Oral cocaine as a reinforcer: acquisition conditions and importance of stimulus
      control.
AB  - Schedule-induced polydipsia in rats was established in daily, 3h sessions with a
      fixed-interval 1min food schedule, and continued with two fluids available on
      concurrent fixed-ratio 6 schedules. A 2% ethanol solution was preferred to water,
      and succeeding drug solutions (0.16mg/ml cocaine, 0.1mg/ml caffeine, 0.01mg/ml
      nicotine, 0.11mg/ml lidocaine) also were preferred. Except for lidocaine, these
      drugs are known to function as reinforcers. Drug solution position was alternated
      daily, with location indicated by a discriminative stimulus (S(D)) light.
      Subsequent S(D) manipulations indicated that lidocaine and cocaine preferences
      were attributable to the prior association of the S(D) with ethanol rather than
      to the pharmacological effects of the currently accessible drug. Furthermore,
      when concurrent water choices were instituted, animals continued to choose the
      water source indicated by the S(D). The effectiveness and durability of the S(D)
      in determining polydipsic choice attests to the importance of the associative
      history of environmental S(D)s in triggering and maintaining drug seeking and
      drug taking. A model is outlined which suggests that drug abuse is a special case
      of a more general set of excessive behaviors induced by current environmental
      conditions, with choice of behavior remaining under S(D) control determined, in
      part, by the associative history of the S(D).

PMID- 11224230
TI  - Dose-dependent discriminative stimulus properties of 8-OH-DPAT.
AB  - Separate groups of rats were trained to discriminate either 0.1mg/kg (low dose;
      L) or 2.5mg/kg (high dose; H) of 8-OH-DPAT from saline, in a standard operant
      task. Both cues were found to be dose, time and route dependent and generalized
      completely to the 5-HT(1A) agonists ipsapirone and flesinoxan. Buspirone
      substituted completely for 8-OH-DPAT in L and partially in H, whereas the 5
      HT(1A/1B) receptor agonist eltoprazine substituted completely for 8-OH-DPAT in H
      but only partially in L. The 5-HT(1A/1B) receptor agonist RU24969, the 5
      HT(1B/2C/1A) receptor agonist TFMPP and the 5-HT reuptake blocker fluvoxamine did
      not completely mimic the effect of 8-OH-DPAT in either L or H and the 5-HT(1A)
      mixed agonists/antagonists BMY 7378 and NAN-190 produced partial generalization
      in L, but no generalization in H. In antagonism tests, NAN-190 and BMY 7378 only
      partially blocked the 8-OH-DPAT cue in both groups. The non-selective 5-HT
      receptor antagonist methysergide did not completely block the 8-OH-DPAT cue in in
      L or H. However, in generalization studies, it completely mimicked the 8-OH-DPAT
      cue in L and produced partial generalization in H. The beta-adrenergic/5
      HT(1A/1B) receptor antagonist pindolol completely blocked the 8-OH-DPAT cue in L
      and H and did not mimic the 8-OH-DPAT cue in either condition. The alpha(2)
      adrenoceptor blocker yohimbine substituted fully for the 8-OH-DPAT cue in L and
      partially in H. Idazoxan did not substitute for the cue of 8-OH-DPAT in H, but
      produced nearly 80% generalization in L. The dopamine receptor antagonist
      pimozide neither blocked nor mimicked the cue of 8-OH-DPAT in either group. A
      number of other drugs (i.e. m-CPP, S(-)-propranolol, DOI, ketanserin, clonidine
      and apomorphine) were only tested in H. S(-)-Propranolol blocked the 8-OH-DPAT
      cue but the other compounds produced neither stimulus generalization nor
      antagonism. The present study demonstrates that the cues produced by the low and
      the high training dose of 8-OH-DPAT are quantitatively different and mediated by
      the agonistic activity of 8-OH-DPAT at 5-HT(1A) receptors. Although the results
      suggest that the 8-OH-DPAT cue (both L and H) is mediated via postsynaptic 5
      HT(1A) receptors, the involvement of presynaptic 5-HT(1A) receptors cannot yet be
      ruled out.

PMID- 11224231
TI  - Neuroanatomical basis for the antidepressant-like effects of the 5-HT(1A)
      receptor agonists 8-OH-DPAT and ipsapirone in the rat forced swimming test.
AB  - In the rat forced swimming test, systemic application of the serotonin 1A (5
      HT(1A)) receptor agonist 8-OH-DPAT reduced immobility (ID(50) 0.17-1.37mg/kg,
      depending on route of application and application schedule).
      Intracerebroventricular (i.c.v.) or local application into the dorsal raphe
      nucleus (DRN), a brain area rich in presynaptic 5-HT(1A) receptors, resulted in a
      parallel shift of the dose-response curve to the left (ID(50) 5.1 and 3.9ug/rat,
      respectively). Systemic application of the 5-HT(1A) receptor partial agonist
      ipsapirone resulted in a U-shaped dose-response curve (maximal effect about 30%
      immobility reduction at 3-10mg/kg). Local application of ipsapirone in the DRN
      reduced immobility (maximal effect 40% at 60ug/rat). However, 8-OH-DPAT and
      ipsapirone were still effective after depletion of brain 5-HT by means of 5,7-DHT
      (150ug, i.c.v.) or pCPA (either 2 x 150mg/kg or 2 x 350mg/kg, i.p.) Additionally,
      in non-lesioned rats: (1) the putative (postsynaptic) 5-HT(1A) antagonist NAN
      190, but not spiperone, haloperidol, prazosin or 1-PP, was able to block the anti
      immobility effects of 8-OH-DPAT in a behaviorally specific manner; (2) local
      application of 8-OH-DPAT and ipsapirone in the lateral septum (a brain area rich
      in postsynaptic 5-HT(1A) receptors) reduced immobility (8-OH-DPAT: ID(50)
      11.4ug/rat; ipsapirone; maximal effect at 30ug/rat 38%); and (3) pretreatment
      with ipsapirone resulted in an attenuation of the effect of 8-OH-DPAT when both
      compounds were administered either systemically or in the lateral septum but not
      when both compounds were microinjected into the DRN. It is hypothesized that the
      anti-immobility effects of 5-HT(1A) receptor agonists are mediated by pre- and
      postsynaptic 5-HT(1A) receptors and that they closely reflect the intrinsic
      activity of these compounds at these receptors.

PMID- 11224232
TI  - The free-exploratory paradigm: an effective method for measuring neophobic
      behaviour in mice and testing potential neophobia-reducing drugs.
AB  - When given the opportunity to choose between a novel and a familiar compartment
      (free-exploratory paradigm), BALB/c mice exhibited a preference for familiar
      places and a marked number of attempts at entry into the novel compartment
      followed by avoidance responses. In contrast, C57BL/6 mice showed a preference
      for novel places and very few avoidance responses towards novelty. When novelty
      was reduced by two familiar odours, fresh sawdust or urine of conspecifics, the
      neophobia of the BALB/c mice was reversed and the animals clearly showed a
      preference for the novel compartment. This experimental paradigm can be proposed
      as an effective animal model for investigating drugs potentially able to reduce
      neophobia in BALB/c mice. The effects of anxiolytics, effective in the usual
      animal models of "state" anxiety, were investigated in the free-exploratory
      paradigm which may model another type of anxiety, termed by Lister (1990) "trait"
      anxiety. Thus, the behavioural effects of two benzodiazepine full agonists,
      chlordiazepoxide and diazepam, two non-benzodiazepine partial agonists at
      benzodiazepine receptors, Ro 19-8022 and alpidem, the 5-HT(1A) receptor agonist,
      8-OH-DPAT, and the 5-HT(3) receptor antagonist, zacopride, were assessed in
      BALB/c and C57BL/6 mice. Chlordiazepoxide, diazepam and Ro 19-8022 completely
      reversed the preference of BALB/c mice for the familiar compartment, treated
      animals exhibiting a significant preference for novel places. In contrast,
      alpidem, 8-OH-DPAT and zacopride did not significantly modify their behaviour.
      Moreover, the same drugs did not modify the specific responses of C57BL/6 mice
      toward novelty. These results demonstrate that drugs which bind in a non
      selective manner to heterogeneous benzodiazepine recognition sites were very
      effective in reducing neophobia in BALB/c mice, whereas 5-HT-interacting drugs
      were unable to counteract their neophobic behaviour. Thus, the free-exploratory
      paradigm can be proposed as an effective method for testing potential neophobia
      ("trait" anxiety) reducing drugs.

PMID- 11224233
TI  - Inhibition of mu opioid-induced motor activity in the ventral pallidum by D1
      receptor blockade.
AB  - Microinjection of the mu opioid, [D-Ala(2), N-Me-Phe(4), Gly-ol(5)]-enkephalin
      (DAMGO) into the ventral pallidum (VP) elicits a motor stimulant response. The
      coadministration of dopamine (DA) antagonists with DAMGO into the VP was used to
      determine the role of DA transmission in the motor response. The mixed D1/D2
      antagonist, fluphenazine, was found to produce a partial reduction in DAMGO
      induced motor activity. To evaluate the role of DA receptor subtypes, the D1 and
      D2 selective antagonists, SCH-23390 and raclopride, respectively, were
      coadministered with DAMGO into the VP. SCH-23390 was found to produce a dose
      dependent reduction in both horizontal and vertical motor activity with a minimum
      effective dose of 0.3nmol/side. However, only a partial reduction in horizontal
      activity occurred with a dose of SCH-23390 as high as 6.0nmol/side. Raclopride
      was without effect at any dose examined, and an equimolar mixture of SCH-23390
      and raclopride did not alter the minimum effective dose nor the maximum reduction
      in motor activity produced by SCH-23390 alone. It is concluded that stimulation
      of D1 receptors is permissive to the motor stimulant effect elicited by DAMGO in
      the VP.

PMID- 11224234
TI  - Blockade of the acquisition of cocaine self-administration by the NMDA antagonist
      MK-801 (dizocilpine).
AB  - In an attempt to assess the contribution of the NMDA receptor system to the
      development of cocaine self-administration, acquisition of intravenous self
      administration (0.25mg/kg/infusion) was assessed in rats that received
      pretreatment with MK-801 (0.0, 0.1 or 0.25mg/kg). For control rats, reliable self
      administration was obtained in 3-8 days of testing. These rats rapidly
      discriminated between depression of a lever that resulted in the delivery of
      cocaine and an inactive lever. Within the initial 10 day test period, most of the
      rats pretreated with MK-801 failed to acquire a preference for an active lever
      which, when depressed, resulted in a cocaine infusion: responding was generally
      high on both the cocaine reinforced and inactive lever. For six rats, MK-801
      treatment was discontinued after 10 days. Although some of these rats had
      received substantial exposure to cocaine during the initial 10 days, self
      administration subsequent to the termination of treatment progressed either with
      a time course comparable to cocaine-naive rats, or not at all. For rats that
      continued to receive MK-801 treatment, most failed to acquire reliable self
      administration within the 18 day test period. These data suggest that the
      glutamatergic NMDA receptor system plays an important role in the establishment
      of cocaine as an effective reinforcer.

PMID- 11224235
TI  - D1 receptor blockade stereospecifically impairs the acquisition of drug
      conditioned place preference and place aversion.
AB  - The motivational effects of dopamine (DA) D1 receptor blockade and its influence
      on the motivational effects of amphetamine (1.0mg/kg s.c.), morphine (1.0mg/kg
      s.c.) and lithium (40mg/kg s.c.) were studied in a place-conditioning paradigm.
      Drugs tested were two potent D1 receptor antagonists, SCH 23390 and SCH 39166,
      that differ in the poor affinity of the latter for 5-HT(2) receptors, and SCH
      23388, the inactive enantiomer of SCH 23390. SCH 23390 and SCH 39166, at low
      doses (12.5 and 25ug/kg s.c.), paired for 30min with one compartment, elicited
      place aversion. Higher doses of the D1 antagonists or pairing for 60min with one
      compartment failed to elicit place aversion. SCH 39166 (50ug/kg s.c.) paired with
      both compartments completely prevented the place-aversion elicited by SCH 23390
      (12.5ug/kg s.c.). SCH 23390 and SCH 39166 at low doses (12.5 and 25ug/kg s.c.
      respectively), paired with both compartments, abolished amphetamine-induced place
      preference. The D1 antagonists also impaired the acquisition of morphine-induced
      place preference and lithium-induced place aversion but only at higher doses (50
      and 100ug/kg s.c.). These effects were stereospecific as the inactive enantiomer
      SCH 23388, up to a dose of 500ug/kg s.c. failed to impair the acquisition of
      amphetamine and morphine-induced place preference. It is concluded that DA plays
      a dual role in motivation: one role is that of assigning motivational valence to
      stimuli in relation to changes in DA transmission; another role of DA relates to
      the learning process involved in the acquisition of positive as well as negative
      incentive properties by otherwise neutral stimuli (incentive learning).

PMID- 11224236
TI  - Chronic morphine affects working memory during treatment and withdrawal in rats:
      possible residual long-term impairment.
AB  - An eight-arm radial maze was used to investigate a possible short-term (during
      the development of tolerance and dependence) and long-term (6, 9 and 12 months
      after treatment) effect on working memory, in young rats, which drank morphine
      (0.5mg/ml) for 1 month, or to which the drug was administered by i.p. injection
      (at weekly increasing doses of 20, 50, 100, 200mg/kg). Tail flick test and
      cortically derived electroencephalographic (EEG) recordings were also carried out
      in the same rats to determine any modifications in analgesia and in total EEG
      mean power spectra during treatment and withdrawal. Complete tolerance to
      morphine analgesia developed during the period of drug treatment. Chronic
      morphine significantly impaired radial maze performance in the working memory
      components of the task during both treatment and early withdrawal, but only in
      the i.p. group. Six and 9 months after morphine treatment, both the oral and i.p.
      group showed a significant impairment of radial maze performance. The mean power
      spectra were altered during treatment but returned to baseline values during
      abstinence, except for the first day. These findings suggest the possibility of
      morphine-induced premature ageing, which is more evident in i.p. treated animals.
      The mechanism by which morphine treatment produces residual long-term learning
      impairment requires further elucidation.

PMID- 11224237
TI  - Persistence of tolerance to effects of cocaine on schedule-controlled behavior in
      pigeons.
AB  - Keypecking by seven pigeons, maintained by a fixed-ratio 30 schedule of food
      presentation, was decreased in rate by acute pre-session administration of
      cocaine. In Part 1 (four pigeons), tolerance to the rate-suppressing effects of
      cocaine developed during daily administration conditions. Tolerance persisted (1)
      when daily cocaine injections were replaced by conditions in which cocaine was
      administered every other day, then every fourth day, then every eighth day, then
      every 16th day, with all intervening sessions preceded by saline injections and
      (2) when daily cocaine administration was replaced abruptly by a condition in
      which cocaine injections were spaced 16 days apart, with all intervening sessions
      preceded by saline. In Part 2 (three pigeons), tolerance developed during
      intermittent administration conditions (e.g. cocaine injected every eighth day)
      for two subjects, and during daily administration for the third subject. As in
      Part 1, tolerance persisted when cocaine was administered only once every 16
      days. These results are consistent with an interpretation of tolerance based upon
      operant compensatory reactions to drug-induced behavioral disruptions and suggest
      that a simple associationist model of tolerance to cocaine-induced response-rate
      suppression may be inadequate. The data also have practical implications
      regarding tolerance development during intermittent administration conditions
      similar to conventional acute dose-effect determination procedures.

PMID- 11224238
TI  - Blockade of the discriminative stimulus effects of d-amphetamine in rhesus
      monkeys with serotonin 5-HT(1A) agonists.
AB  - Rhesus monkeys (n = 4) were trained in a two-lever drug discrimination paradigm
      to discriminate d-amphetamine (AMPH; 0.56 or 1.0mg/kg, i.g., 60min pre-session)
      from saline. Lever pressing was maintained under a discrete-trials shock
      avoidance schedule of reinforcement (30 trials/day, 30-s intertrial interval,
      fixed-ratio 1). Before test sessions, in which responding on either lever avoided
      shock, the monkeys were infused (i.g.) with saline or various doses of AMPH (0.1
      1.7mg/kg), alone or in combination with intramuscular injections of the serotonin
      (5-HT(1A)) agonists buspirone (0.3-1.0mg/kg), gepirone (0.56-3.0mg/kg), 8-hydroxy
      2(di-n-propylamino) tetralin (8-OH-DPAT; 0.01-0.1mg/kg), the dopamine D2
      antagonist raclopride (0.03 and 0.1mg/kg), or pentobarbital (10mg/kg). Doses of
      the 5-HT(1A) agonists and raclopride, which occasioned only saline-lever
      responding when tested alone, shifted the AMPH dose-response function 0.5 to 1.0
      log unit to the right in all monkeys, while pentobarbital had no effect. For the
      5-HT(1A) agonists, the order of potency for attenuating the AMPH discriminative
      stimulus was 8-OH-DPAT>buspirone>gepirone, similar to their binding affinities at
      5-HT(1A) receptors. Raclopride was equipotent to 8-OH-DPAT. In addition, although
      the effect of buspirone and gepirone could be surmounted by increasing the dose
      of AMPH, the effect of 8-OH-DPAT, the 5-HT(1A) agonist with the highest intrinsic
      activity (efficacy), was insurmountable in two of the three monkeys tested. These
      results suggest that the discriminative stimulus effect of AMPH can be modulated
      by stimulation of 5-HT(1A) receptors to an extent comparable with that seen with
      a D2 antagonist. Further, these results suggest that 5-HT(1A) agonists may
      attenuate the subjective effects of psychomotor stimulants in humans.

PMID- 11224239
TI  - Effect of the competitive NMDA antagonist, CGP 40 116, and a low dose of l-Dopa
      on the motor activity deficit of MPTP-treated mice.
AB  - Three experiments were performed to investigate the effects of combining the
      active D-stereoisomer of CGP 37 849, i.e. the glutamatergic antagonist, CGP 40
      116, with l-dopa, in mice that had undergone treatment with the neurotoxin, MPTP.
      In the first experiment, the decreased motor activity in MPTP-treated mice was
      alleviated by the administration of a low dose of l-dopa (5mg/kg, s.c.) together
      with a low dose of CGP 40 116 (30ug/kg). This dose was inactive in the control
      (saline-treated) mice. The highest dose of CGP 40 116 used (3000ug/kg) stimulated
      activity in the control mice. In Experiment 2, the inactive L-stereoisomer, i.e.,
      CGP 40 117, was found to be inactive at doses (3 and 30ug/kg) effective with CGP
      40 116. The effects of CGP 40 116 and l-dopa on the 24-h activity of mice tested
      under either day-night or night-day conditions, were more marked and longer
      lasting in the night-day condition. Taken together, the results from all three
      experiments show that CGP 40 116 in a dose range of 1-30ug/kg in combination with
      l-dopa (5mg/kg, s.c.) alleviated the reduced motor activity in MPTP-treated mice
      whereas higher doses of CGP 40 116 (100, 300, or 3000ug/kg) or lower doses (0.1
      and 0.3ug/kg) were without effect. These experiments are interpreted as support
      for current views on glutamatergic-dopaminergic interactions in Parkinsonism and
      offer further evidence for the MPTP mouse model of the disease.

PMID- 11224240
TI  - Behavioral effects of acute and chronic cocaine administration in male and female
      rats: effects of fixed-ratio schedule parameters.
AB  - Intact and gonadectomized male and female rats pressed a lever to obtain food on
      different fixed-ratio (FR) schedules in a three-component multiple schedule. The
      values of a small, intermediate and large FR schedule were individually
      determined and were higher for intact male rats than for most subjects in the
      other groups. Acute cocaine administration (1.0-30.0mg/kg) dose-dependently
      decreased response rates maintained by all three schedules, but responding
      maintained by the large FR schedule was more sensitive to the rate-decreasing
      effects of acute cocaine administration. Response rates of intact male rats were
      less sensitive to the rate-decreasing effects of cocaine than those of the other
      groups, at least at higher doses during the small and intermediate FR schedules.
      Cocaine's dose-effect curve was redetermined after chronic administration of a
      behaviorally active dose of cocaine. Differences between groups of subjects were
      not evident. Behavioral tolerance was consistently observed when responding was
      maintained by the small FR schedule. Effects varied between subjects within
      groups when responding was maintained by the intermediate FR schedule, but
      behavioral tolerance was frequently observed. Behavioral sensitization was
      evident during the large FR schedule, but these data were difficult to interpret
      because of a considerable shift in response rates after vehicle administration.
      The data suggest that the comparison of drug effects in male and female rats
      requires a systematic analysis of the contribution of behavioral parameters. They
      also provide additional evidence for the notion that reference to reinforcement
      loss alone is not sufficient to explain the development of tolerance to the
      behavioral effects of cocaine.

PMID- 11224241
TI  - Parametric studies of selective D1 or D2 antagonists: effects on appetitive and
      feeding behaviour.
AB  - Dopamine receptor antagonists have long been known to suppress food intake. The
      main purpose of the present series of experiments was to investigate feeding in
      rats across several paradigms evaluating the effects of selective dopamine D1 and
      D2 antagonists. The selective D1 antagonist, SCH 23390, reduced FR8 operant
      responding for food (0.03mg/kg, s.c.) at a dose lower than that required to
      reduce food intake in two free-feeding situations (0.1mg/kg, s.c.). The selective
      D2 antagonist, YM 09151-2, had a biphasic effect on food intake in food-deprived
      rats, increasing food intake at a low dose (0.01mg/kg, i.p.), but decreasing
      intake at higher doses in deprived rats (0.1mg/kg, i.p.). A combination of
      subthreshold doses of SCH 23390 and YM 09151-2 resulted in a significant
      reduction in food intake. In nondeprived rats eating palatable food and in
      animals trained on an FR8 schedule of reinforcement, YM09151-2 exerted
      significant suppressant effects. The results suggest that the operant response is
      more sensitive to the effects of selective D1 and D2 antagonism than is the
      consummatory response. The findings also suggest a specific inhibitory role for
      dopamine D2 (and not D1) receptors on food intake, since selective D1 antagonism
      did not produce increases in food intake at any of the doses tested. This
      provides evidence that under some circumstances the effects of D1 and D2 receptor
      blockade are dissociable.

PMID- 11224242
TI  - Genetic differences in the locomotor response to single and daily doses of
      phencyclidine in inbred mouse strains.
AB  - Genetic differences in the locomotor stimulant effects of both single and daily
      administration of phencyclidine were investigated in four inbred strains of male
      mice A/J, C57BL/6J, C57BL/6ByJ and BALB/cByJ. Each mouse was injected i.p. once
      in Experiment 1, or daily for 5 or 11 days in Experiments 2, 3 and 4. Locomotor
      activity was assessed with an automated photoelectric system. Significant strain
      differences were found in the response to a single as well as repeated doses of
      phencyclidine. A/J mice showed the greatest initial response to phencyclidine and
      developed tolerance to daily phencyclidine. C57BL/6ByJ mice showed initial
      resistance to acute phencyclidine, but developed sensitization to daily
      phencyclidine. The responses of both C57BL/6J and BALB/cByJ mice to acute
      phencyclidine were low to moderate, and did not change significantly following
      daily phencyclidine. The results of this study indicate that different genetic
      mechanisms are involved in responses to single and daily injections of
      phencyclidine.

PMID- 11224243
TI  - Discriminative stimulus effects of combinations of drug and visual stimuli in
      pigeons.
AB  - Six pigeons were studied to determine whether the brightness of a houselight
      interacted with the stimuli produced by methadone, and whether the nature of the
      interaction depended on the order of training of the two discriminations. Three
      pigeons were trained to peck the right key after methadone (2.0mg/kg) and the
      left key after saline, when the houselight was dim. The effects of a range of
      methadone doses (0.5, 1.0, 2.0mg/kg and saline) were tested. Three other pigeons
      were trained, in the absence of drug, to peck the right key when the houselight
      was dim and the left key when the houselight was bright. The effects of a range
      of houselight intensities were tested. Then, for both groups, right-key pecks
      were reinforced in the presence of methadone and the dim houselight, and left-key
      pecks were reinforced in the presence of saline and the bright houselight.
      Methadone doses were tested in the presence of both houselight brightnesses used
      in training. All pigeons pecked the methadone-appropriate key after high doses of
      methadone, regardless of houselight intensity. All pigeons trained to
      discriminate houselight brightness first, and one of the pigeons trained to
      discriminate methadone first, pecked according to the houselight condition when
      saline and lower doses were tested. In the other pigeon trained to discriminate
      methadone first, pecking was more related to drug dose. These data show that a
      drug stimulus can compete with external stimuli for behavioral control, that a
      drug stimulus can assume control over behavior originally controlled by external
      stimuli, and that discriminations based on external stimuli may be retained when
      saline or low doses of drug are administered.

PMID- 11224244
TI  - Flumazenil antagonizes the effect of diazepam on negative contrast in one-way
      avoidance learning.
AB  - The main aim of the present work was to study whether the effect of diazepam upon
      successive negative contrast in one-way avoidance learning-induced by shifting
      rats from a large reward (30s spent in the safe compartment) to a small reward
      (1s)-is mediated by the action of this drug on the benzodiazepine (BZ) receptor.
      Therefore, we studied the influence of flumazenil (FL), a BZ antagonist, on the
      effect of diazepam (DZ) on negative contrast. The i.p. administration of 5 and
      12mg/kg, but not of 2mg/kg of FL, reliably antagonized the abolition by DZ
      (1mg/kg) on successive negative contrast. Moreover, FL (12mg/kg) did not affect
      either the avoidance response or the contrast effect. These results suggest that
      the GABA system is involved in the successive negative contrast effect in one-way
      avoidance learning, and that this experimental procedure may be useful in studies
      of anti-anxiety agents.

PMID- 11224245
TI  - Evidence that tolerance to the anxiogenic-like effects of mCPP does not involve
      alteration in the function of 5-HT(2C) receptors in the rat choroid plexus.
AB  - The mechanisms by which 1-(3-chlorophenyl) piperazine (mCPP) causes anxiety are
      unclear, but it has been suggested that the serotonin 5-HT(2C) receptor subtype
      may be involved in this effect. We have therefore studied the effect of chronic
      treatment (3 weeks) with mCPP in two animal models of anxiety (light/dark choice
      task in mice and elevated plus-maze test in rats) and subsequently assessed the
      function of 5-HT(2C) receptors (measured by maximal stimulation of 5-HT(2C)
      receptor-mediated phosphoinositide hydrolysis) in rat choroid plexus, where the
      receptor is present at very high levels. mCPP treatment regimens led to a
      tolerance to the anxiogenic-like action of the drug, but failed to alter the
      second messenger coupling of the 5-HT(2C) receptors in the choroid plexus,
      thereby suggesting the involvement of different mechanisms in this behavioral
      effect.

PMID- 11224246
TI  - Differential effects of anxiolytic and non-anxiolytic benzodiazepine receptor
      ligands on performance of a differential reinforcement of low rate (DRL)
      schedule.
AB  - The effects of several drugs acting at central benzodiazepine receptors on
      performance of a differential reinforcement of low rate (DRL) 15s schedule of
      reinforcement for food reward were studied in rats. The non-selective full
      agonists diazepam (0.1, 1.25, 5 and 10mg/kg) and lorazepam (0.1, 0.25, 0.375 and
      0.5mg/kg) increased total numbers of responses and decreased the numbers of
      reinforcements received, increased burst responding (responding within 3s of a
      previous response), and produced a shift in the interresponse time (IRT)
      distribution of responses towards shorter intervals. The beta-carboline
      anxiolytic abecarnil (0.039, 0.156, 0.313 and 0.625mg/kg) was more potent than
      the two benzodiazepines, but otherwise gave rise to similar changes in
      performance. Bretazenil (0.1, 1.0, 10 and 30mg/kg), a non-selective partial
      agonist, and CL 218872 (3, 10, and 30mg/kg), a partial agonist showing preference
      for the BZ1 receptor subtype, also increased response rates and decreased numbers
      of reinforcements, but failed to increase significantly burst responding, and had
      only weak effects in shifting the IRT distribution. Alpidem (1, 3, 10, 30 and
      100mg/kg) and zolpidem (0.33, 1, 3 and 10mg/kg), two imidazopyridines showing BZ1
      preference, but classified respectively as an anxiolytic and a selective hypnotic
      agent, non-significantly reduced response rates and significantly reduced the
      numbers of reinforcements, but did not influence burst responding, and had
      effects on IRT distribution only at single doses. Thus, in general, the effects
      of these compounds on DRL performance reflect their activity in conflict models.
      The differential effects on DRL performance of the benzodiazepine receptor
      ligands tested may be attributable to their abilities to interact selectively as
      agonists or partial agonists at different benzodiazepine receptor subtypes.

PMID- 11224247
TI  - Discrimination among morphine, saline and naltrexone in rhesus monkeys receiving
      morphine subchronically.
AB  - Discriminative control was established among morphine, saline and naltrexone in
      rhesus monkeys receiving morphine every other day. Three hours prior to sessions
      subjects received saline or 3.2mg/kg morphine; immediately prior to sessions they
      received saline or 0.01mg/kg of naltrexone. There were dose-related
      generalizations to each training condition: morphine generalized to the morphine
      plus saline lever; small doses of naltrexone reversed effects of morphine and
      larger doses occasioned responding on the morphine plus naltrexone lever; in one
      monkey still larger doses occasioned responding on the saline plus saline lever.
      When saline was administered 3h earlier, naltrexone had no effect in one subject
      and occasioned responding on the morphine plus naltrexone lever in a second
      subject. Nalbuphine substituted for morphine plus saline in one monkey and for
      morphine plus naltrexone in a second monkey; ketamine did not substitute for
      either training drug. That stimulus control was established between no drug and a
      combination of morphine and naltrexone suggests the latter condition did not
      represent the absence of morphine. In addition to demonstrating stimulus control
      for three conditions in rhesus monkeys, the current study suggests opioid
      antagonists might have novel discriminative stimulus effects at opioid receptors
      even under conditions where signs of withdrawal are not evident.

PMID- 11224248
TI  - Opioid modulation of the discriminative stimulus effects of cocaine: comparison
      of u, kappa and delta agonists in squirrel monkeys discriminating low doses of
      cocaine.
AB  - Modulation of the discriminative stimulus effects of cocaine by the u agonist
      morphine, the kappa agonist U 50, 488, and the delta agonist BW 373U86 was
      investigated in squirrel monkeys using a two-lever drug discrimination procedure.
      Monkeys initially were trained to discriminate intramuscular injections of 0.3 or
      0.56mg/kg cocaine from vehicle and subsequently retrained to discriminate a 3- to
      5.6-fold lower dose of cocaine (0.1 or 0.18mg/kg). After retraining, dose
      response functions for the discriminative stimulus effects of cocaine were
      shifted to the left and ED(50) values were reduced 2- to 6-fold compared to
      values obtained with the higher training doses. In drug substitution experiments,
      morphine (0.03-1.0mg/kg), U 50,488 (0.1-3.0mg/kg) and BW 373U86 (0.001-0.1mg/kg)
      did not reproduce the discriminative stimulus effects of the low training doses
      of cocaine, although U 50,488 engendered a majority of responses on the cocaine
      associated lever in two of three monkeys. In drug interaction experiments,
      pretreatment with morphine (0.3mg/kg) potentiated the discriminative stimulus
      effects of the low training doses of cocaine such that the cocaine dose-response
      functions were shifted to the left and ED(50) values were reduced 3- to 7-fold.
      Pretreatment with U 50,488 (0.3mg/kg), on the other hand, attenuated the
      discriminative stimulus effects of the low training doses of cocaine such that
      the cocaine dose-response functions were shifted to the right and ED(50) values
      were increased approximately 4-fold. The cocaine-modulating effects of morphine
      and U 50,488 in these experiments were qualitatively similar to those observed
      previously when the monkeys were trained to discriminate higher doses of cocaine.
      In contrast to the effects of the u and kappa agonists, pretreatment with BW
      373U86 (0.01 or 0.03mg/kg) did not systematically alter the discriminative
      stimulus effects of cocaine regardless of training dose.

PMID- 11224249
TI  - The effects of amphetamine, phencyclidine, dopaminergic antagonists and atypical
      neuroleptics on schedule-induced polydipsia (SIP) are distinguishable.
AB  - The effects of amphetamine, phencyclidine, dopaminergic blockers and atypical
      neuroleptics on the acquisition of schedule-induced polydipsia in rats were
      compared in a chronic dose regime followed by 7 days of withdrawal. All compounds
      suppressed water intake. However, different mechanisms were responsible. The
      antidopaminergic compounds inhibited the initiation of drinking, as the temporal
      pattern of licking was shifted to the right. Phencyclidine inhibited the
      maintenance of drinking as the number of licks/ml water consumed was increased.
      The suppressing effect of amphetamine may have been due to the reduction of high
      rates of licking and/or a competition between licking and locomotor or other
      amphetamine-induced activities. The number of panel entries were increased by
      amphetamine and phencyclidine. The typical antidopaminergic compounds decreased
      the number of panel pushes, whereas the atypical antidopaminergic compounds were
      without effect on this parameter. In conclusion, it was possible to differentiate
      between the types of compounds investigated by comparing their effects on water
      intake, panel pressing, drinking efficiency and the temporal patterns of licking
      and panel pressing.

PMID- 11224250
TI  - Noradrenaline-serotonin interactions in the anxiolytic effects of 5-HT(1A)
      agonists.
AB  - The purpose of this study was to analyse adrenergic and serotonergic interactions
      in the anxiolytic effects of several 5-HT(1A) agonists including ipsapirone,
      buspirone, indorenate and 8-OH-DPAT. To this end, the effects of different doses
      of the adrenergic compounds clonidine (0.015-0.0625mg/kg), yohimbine (0.125
      0.5mg/kg), prazosin (0.5-2.0mg/kg), pindolol (1.55-6.2mg/kg) and practolol (0.25
      1.0mg/kg) on defensive burying behaviour were established. Clonidine (0.015
      0.0625mg/kg), prazosin (1.0 and 2.0mg/kg), pindolol (1.55 and 6.2mg/kg) and all 5
      HT(1A) agonists reduced burying behaviour by themselves. In contrast, yohimbine
      (0.250 and 0.5mg/kg) increased, while practolol did not modify, this behaviour.
      Additionally, the actions of yohimbine (0.125mg/kg), prazosin (0.5mg/kg),
      pindolol (3.1mg/kg) and practolol (0.5mg/kg) on the effects of ipsapirone
      (5.0mg/kg), buspirone (5.0mg/kg), indorenate (5.0mg/kg) and 8-OH-DPAT (0.25mg/kg)
      were examined. Prazosin enhanced the effects of ipsapirone, indorenate and
      buspirone, while yohimbine antagonized the actions of indorenate and 8-OH-DPAT.
      Pindolol enhanced the effects of indorenate while practolol antagonized the
      actions of ipsapirone, buspirone and 8-OH-DPAT. Only buspirone (5.0mg/kg)
      affected motor coordination, an effect that was not counteracted by the
      antagonists. Based on these data an interaction between 5-HT(1A) agonists and the
      noradrenergic system in the regulation of anxiety is proposed.

PMID- 11224251
TI  - Affiliation and neophobia in developing mice prenatally exposed to oxazepam.
AB  - In the framework of the well-known regulatory role of the GABA-benzodiazepine
      (BZ) mechanisms of the brain in response to social and environmental challenges,
      we tested the hypothesis that developmental manipulation of this neurochemical
      system by prenatal BZ exposure can affect the social repertoire and neophobia
      level in infant mice. Outbred CD-1 mice were treated with either vehicle or
      oxazepam (15mg/kg p.o. to the dam, twice a day on Days 12-16 of foetal life), and
      fostered at birth to untreated dams. Two males plus two females were observed in
      the home cage, in the presence of a novel object, on Postnatal Days 16, 20 and
      24. The expression of social and non-social behaviours increased with age.
      Prenatal oxazepam exposure reduced sex differences by having a more pronounced
      effect on males than on females; it also produced fairly specific, though subtle,
      behavioural changes. Oxazepam exposed mice appeared more involved than prenatal
      controls in behaviours related to the achievement and maintenance of a "passive"
      proximity with littermates. By contrast, they performed less active investigation
      and solicitation of littermates, and non-social behaviours such as locomotor
      rotational play, cage exploration, and maintenance activities; they also showed a
      reduced frequency of approaching and making contact with the novel object.
      Analysis of social interactions of infant mice seems to represent a sensitive
      tool for early detection of subtle developmental changes in the CNS.

PMID- 11224252
TI  - Assessment of the relative intrinsic efficacy of profadol and meperidine in a
      pigeon drug discrimination procedure: relevance to partial substitution patterns.
AB  - Substitution and antagonism patterns of butorphanol, meperidine and profadol were
      examined in pigeons trained to discriminate either a 0.056 (low) or 0.18 (high)
      mg/kg dose of fentanyl from saline. In the low-dose group, fentanyl, meperidine,
      profadol and butorphanol substituted completely (>/=85% fentanyl-appropriate
      responding) for the fentanyl stimulus. For fentanyl and butorphanol, complete
      substitution was obtained at doses that had little effect on rates of responding,
      whereas profadol substituted at doses that moderately decreased rates and
      meperidine substituted at doses that markedly decreased rates. Although naloxone
      antagonized the stimulus effects of meperidine and profadol, it failed to alter
      their rate-decreasing effects. In the high-dose group, fentanyl and butorphanol
      substituted completely and meperidine and profadol partially (approximately 50%
      fentanyl-appropriate responding) for the fentanyl stimulus. During antagonism
      tests, meperidine and profadol produced only small decreases (less than 15%) in
      the percentage of fentanyl-appropriate responding produced by the training dose
      of fentanyl. Analysis of individual data indicated that meperidine and profadol
      produced three patterns of substitution and antagonism. In one subgroup of
      pigeons, meperidine and profadol substituted completely for but failed to
      antagonize the fentanyl stimulus; in another, these opioids failed to substitute
      for but did antagonize the fentanyl stimulus; and in another, these opioids
      failed to substitute for or antagonize the fentanyl stimulus. In this latter
      subgroup, meperidine and profadol produced leftward shifts in the dose-effect
      function for the stimulus effects of fentanyl and butorphanol. The present
      findings suggest that the failure of meperidine and profadol to substitute
      completely for the high-dose fentanyl stimulus was a direct consequence of their
      rate-decreasing effects rather than low efficacy at the mu receptor.

PMID- 11224253
TI  - The effects of delta(9)-tetrahydrocannabinol on repeated acquisition and
      performance of response sequences and on self-reports in humans.
AB  - This study assessed the acute effects of delta(9)-tetrahydrocannabinol (THC) on
      learning and performance, using a repeated acquisition and performance paradigm,
      in eight healthy adult humans. Subjective ratings of drug effects were also
      collected. In each component of a multiple schedule, subjects completed a
      different sequence of 10 responses using three keys of a numeric keypad. In the
      acquisition component, subjects learned a new sequence with each series of 20
      trials. In the performance component, the sequence remained constant throughout
      the study. The multiple schedule and rating scales were presented pre-drug, post
      drug and at 30min intervals thereafter for 5h. THC (10-20mg, p.o.) increased the
      peak percentage of errors during the acquisition component from 7.0% to 9.3% but
      responding during the performance component was unchanged. THC decreased Digit
      Symbol Substitution Test performance, increased Profile of Mood State ratings of
      confusion, depression and general mood disturbance and Visual Analog Scale
      ratings of strength of drug effect, good and bad effects, but did not alter
      Addiction Research Center Inventory ratings. In summary, THC in humans caused a
      slight learning deficit at behaviorally active doses under the repeated
      acquisition procedure.

PMID- 11224254
TI  - Effects of buprenorphine on the self-administration of cocaine by humans.
AB  - Seven male research volunteers reporting intravenous cocaine and morphine use
      participated in 12 cocaine self-administration sessions. A session consisted of
      sublingual buprenorphine pretreatment (0, 2, 4mg) 50min before seven self
      administration trials. The first three trials were sampling trials, in which
      subjects were given each of the three reinforcers available for that session; the
      remaining four trials were choice trials in which subjects could choose between
      two doses of cocaine and tokens exchangeable for special privileges. Each
      buprenorphine dose was tested for four consecutive days under different cocaine
      dose/token combinations (e.g. 8mg vs 16mg vs two tokens). Following placebo,
      under all choice conditions, subjects reliably chose higher doses of cocaine over
      lower doses, and tokens about as often as high cocaine doses. Buprenorphine (4mg)
      significantly decreased high-dose cocaine choice and increased token choice, when
      the available cocaine doses were 16 and 32mg/70kg. Both buprenorphine doses
      significantly increased ratings of "sedated" and opiate symptoms and decreased
      ratings of "bad drug effect" following all cocaine doses. Both buprenorphine
      doses, in combination with cocaine doses greater than 8mg, significantly
      increased self-reported "high" and occasionally increased "stimulated" scores
      above values seen following cocaine alone. The results demonstrate that in the
      presence of non-drug alternative to cocaine (tokens), buprenorphine decreased
      high-dose cocaine choice. Despite the decrease, subjects were clearly intoxicated
      from a drug combination that mimicked a cocaine-heroin ("speedball") effect.
      Although buprenorphine may be useful in reducing cocaine use, the complex
      relationship between this reduction in use, behavioral alternatives, and the
      subjective effects of the drug combination remains unclear.

PMID- 11224255
TI  - Social olfactory recognition in rodents: deterioration with age, cerebral
      ischaemia and septal lesion.
AB  - Social olfactory recognition in rodents has been shown to assess short-term
      memory and to be sensitive to cholinergic drugs. It is based on the investigation
      of a juvenile by an adult rat and is measured by a reduction in duration of
      exploration during the second of two successive exposures lasting 5min. The
      present experiments further characterize rodent social recognition in
      pathophysiological models known to impair memory. Social recognition was
      distrupted by ageing in both rats and mice, by vincristine-induced septal lesion
      and by damaging the CA1 hippocampal layer after cerebral ischaemia in rats. These
      memory deficits could be compensated by reducing the time interval between the
      two presentations of the juvenile and/or by prolonging the juvenile encounter.
      Similarly, muscarinic agonists (arecoline, SR 46559A) counterbalanced the memory
      impairment in the three models. The present results indicate that the hippocampus
      plays a key role in social recognition. They suggest that in the three
      pathophysiological models, memory ability is still present although it is of very
      short duration; however, it can still be improved by pharmacological treatments.

PMID- 11224256
TI  - Anxiolytic-like effects of 5-HT(1A) agonists in drug-naive and in benzodiazepine
      experienced rats.
AB  - The efficacy of two 5-HT(1A) receptor agonists in drug-naive and benzodiazepine
      experienced rats was compared in two animal tests of anxiety, the social
      interaction and elevated plus-maze tests. Benzodiazepine-experienced rats were
      tested 48h after the last of 28 daily injections of diazepam (2mg/kg/day), a time
      at which there was no anxiogenic withdrawal response. S20499 (0.04, 0.2 and
      1mg/kg) ((+)-8(4-[N-(5-methoxychroman-3yl)N-propylamine]butyl)-8
      azaspirol[4,5]decane-7,9-dione) and buspirone (0.2mg/kg) significantly increased
      social investigation, indicating anxiolytic-like actions, and there was no
      significant modification in these effects as a result of the previous diazepam
      treatment. Both drugs also significantly reduced aggressive behaviours in both
      drug-naive and diazepam-experienced rats. An anxiolytic-like action in the
      elevated plus-maze was also indicated for S 20499 (0.04 and 0.2mg/kg) by an
      increase in the percentage of time spent on the open arms; this effect was not
      significantly changed by prior diazepam experience. Buspirone (0.2mg/kg) had no
      significant effects on the plus-maze. The results provide no evidence for reduced
      efficacy of 5-HT(1A) receptor agonists in animal tests of anxiety as a result of
      prior diazepam treatment.

PMID- 11224257
TI  - Testosterone implantation reduces the motor effects of cocaine.
AB  - The abuse of anabolic-androgenic steroids noted in recent years has been
      correlated with an increased likelihood of abuse of other drugs, including
      cocaine. This research was designed to investigate whether manipulation of
      androgen levels would alter the unconditioned behavioral effects of cocaine. The
      influence of testosterone on the locomotor activating effect of oral cocaine was
      evaluated. Subjects were male gonadally intact and castrated Wistar rats,
      implanted s.c. with either placebo or 100mg testosterone 30-day pellets.
      Beginning 7 days after pellet implantation, each animal in the four subgroups
      randomly received 0, 20, 40 and 80mg/kg cocaine (once, each dose). Cocaine
      80mg/kg significantly enhanced locomotor activity in all groups except the intact
      testosterone-treated group. Of the four groups, this subgroup would have the
      highest plasma level of testosterone. These data suggest that chronic exogenous
      androgen administration may reduce the behavioral effects of cocaine.

PMID- 11224258
TI  - Effects of caffeine deprivation on taste and mood.
AB  - Despite its ubiquitous consumption in the natural environment, caffeine has not
      been a reliable reinforcer in laboratory settings. The reinforcing effects of
      caffeine are greater in caffeine-dependent subjects relative to non-dependent
      subjects, but the mechanism underlying this difference remains unclear. We
      hypothesized that deprivation from caffeine would produce alterations in
      subjective ratings of stimuli commonly associated with caffeine consumption.
      Specifically, we hypothesized that hedonic ratings of the coffee taste would be
      selectively enhanced following caffeine deprivation. Twelve regular caffeine
      users received acute doses of caffeine (300mg) or placebo after 33h of caffeine
      deprivation or non-deprivation. They rated the taste of coffee and sucrose,
      saccharin, and quinine solutions on intensity, bitterness, sweetness,
      pleasantness, and unpleasantness. Contrary to our hypothesis, subjects' ratings
      of the pleasantness of the coffee taste were not significantly altered by
      caffeine deprivation. However, subjects' ratings of the bitterness and sweetness
      of the coffee taste and ratings of the sucrose solution were altered by caffeine.
      Implications of these data for caffeine self-administration are discussed.

PMID- 11224259
TI  - The effects of the new antipsychotic, sertindole, on latent inhibition in rats.
AB  - Latent inhibition (LI) is a measure of retarded conditioning to a previously
      presented non-reinforced stimulus, that is impaired in schizophrenic patients and
      in rats treated with amphetamine. Neuroleptic drugs are known to produce two
      effects in this paradigm: to antagonize amphetamine-induced disruption of LI, and
      to facilitate the development of LI when administered on their own. The present
      experiments tested the effects on LI of the new neuroleptic, sertindole. The
      experiments used a conditioned emotional response procedure in rats licking for
      water, consisting of three stages: pre-exposure, in which the to-be-conditioned
      stimulus (a tone) was repeatedly presented without being followed by
      reinforcement; conditioning, in which the pre-exposed stimulus was paired with
      reinforcement (a foot shock); and test, in which LI was indexed by degree of
      suppression of licking during tone presentation. In Experiment 1 the effects of
      0.31, 1.3 and 5.0mg/kg sertindole were assessed following pre-exposure to 40 non
      reinforced tones. Experiment 2 tested the effects of 5mg/kg on LI following pre
      exposure to 10 non-reinforced tones. Experiment 3 investigated antagonism of
      amphetamine-induced disruption of LI by 5.0mg/kg sertindole. The results
      demonstrated that sertindole (5.0mg/kg) possesses a neuroleptic-like profile in
      the LI model: it facilitates the development of LI and antagonizes amphetamine
      induced disruption of LI.

PMID- 11224260
TI  - Opioid drugs and timeout from avoidance.
AB  - The effects of u agonists fentanyl, methadone and morphine and kappa agonist
      U50,488 on behavior maintained by negative reinforcement were determined. Rats
      were trained on concurrent schedules in which pressing one lever postponed shock
      on a Sidman avoidance schedule and pressing the other lever produced signaled
      periods of timeout from avoidance on variable-ratio schedules. All of the u
      agonists decreased responding maintained by timeout from avoidance at doses that
      increased or did not affect avoidance rates. The kappa agonist U50,488 decreased
      response rates in some rats, but increased responding in others. In no case was a
      selective reduction in responding on the timeout lever produced by U50,488. Thus,
      the previously reported selective decreases in timeout responding by morphine are
      also produced by u agonists fentanyl and methadone, but not by kappa agonist U50,
      488.

PMID- 11224261
TI  - Assessment of the benzodiazepine-like dependence potential in rats of the
      putative 5-HT(1A) agonist anxiolytic S-20499.
AB  - The dependence potential of the putative 5-HT(1A) agonist anxiolytic S-20499 was
      assessed in rats in a study in which the benzodiazepine chlordiazepoxide (CDP)
      was used as a "positive control". S-20499 was administered b.i.d. (at 10.00 and
      16.00h) for 21 days, at constant doses of either 0.5, 3 or 18mg/kg i.p.
      Subsequently, spontaneous withdrawal from S-20499 was studied over 7 days.
      Acutely, S-20499 decreased body weight and food intake and complete tolerance
      developed to these effects. When S-20499 was withdrawn there was no evidence of
      any effect on body weight or food intake. CDP was also administered b.i.d. (at
      10.00 and 16.00h) for 21 days at doses escalated from 10 to 30mg/kg i.p. CDP
      differed from S-20499 in some of its acute effects, stimulating body weight and
      food intake. In contrast to S-20499 withdrawal, CDP withdrawal induced weight
      loss and aphagia. Acutely, S-20499 resembled CDP in inducing hypothermia. Full
      tolerance developed to this effect of both drugs. However, only CDP withdrawal
      induced hyperthermia. Thus S-20499 appeared to be devoid of benzodiazepine-like
      dependence potential after administration for a relatively long period of time,
      at doses that are substantially greater than "anxiolytic doses" in rats.

PMID- 11224262
TI  - Dopamine antagonist effects on behavior maintained by cocaine and alfentanil in
      rhesus monkeys.
AB  - The effects of dopamine (DA) antagonists that act on either the D1 site (SCH
      39166), the D2 site (eticlopride), or both sites non-selectively (cis
      flupenthixol) were evaluated for their effects on behavior maintained by cocaine
      or alfentanil in rhesus monkeys. Each of these drugs suppressed rates of
      responding maintained by cocaine or alfentanil. Larger doses of each of the DA
      antagonists were necessary to suppress cocaine- as opposed to alfentanil
      maintained responding, suggesting that cocaine but not alfentanil was able to
      antagonize the rate-suppressing effects of the antagonists. There was little
      evidence, under these conditions of acute administration, that the DA antagonists
      modified the reinforcing effects of either cocaine or alfentanil. This would have
      been observed by an antagonist-induced increase in the ED(50) of the reinforcing
      drugs and, although such an increase was seen occasionally with cocaine, it was
      never statistically significant. The effects of rate-suppressing doses of each of
      the antagonists on directly observable behavior indicated a rapid onset and
      relatively short duration of action of intravenously administered SCH 39166 and
      eticlopride. cis-Flupenthixol had a much slower onset of action. Each of the DA
      antagonists produced similar increases in measures of sedation and relaxation.
      These data suggest very similar behavioral effects of DA antagonists that act
      selectively on D1 or D2 receptors or act non-selectively on both DA receptors.

PMID- 11224263
TI  - Interactions between caffeine and cocaine in tests of self-administration.
AB  - Interactions between the effects of cocaine and caffeine have been demonstrated
      in tests of motor activity and drug discrimination. Since both drugs are widely
      consumed by humans, the present study was undertaken to determine whether a
      similar interaction between the reinforcing effects of these drugs could be
      demonstrated. Experienced cocaine self-administering rats were treated with
      caffeine either as an i.p. injection (20.0mg/kg) prior to each self
      administration test or as a co-administered drug within the infusion syringe
      (0.25mg/kg/infusion). Both of these routes of administration of caffeine
      increased the intake of low doses of cocaine. Since caffeine is not reliably self
      administered by laboratory animals, these data suggest that caffeine potentiated
      the reinforcing effects of cocaine.

PMID- 11224264
TI  - Effects of varying the "openness" of an economy on responding for cigarettes.
AB  - The extent to which drugs are consumed may be related to whether they are
      available in a closed or open economy. This study examined the effects of the
      "openness" of an economy on responding for cigarettes during a computer task and
      cigarettes earned. Using a within-subjects design, openness was manipulated by
      varying the number of free (unearned) cigarettes available to subjects during a
      6h post-task period. No free cigarettes were available during the "closed"
      economy session; 5 or 10 free cigarettes were available during the two open
      economy sessions. Subjects performed a concurrent random-ratio (RR) schedule task
      to earn points redeemable for cigarettes or money. The cigarette schedule varied
      within a session from RR1.3 to RR16. Throughout each session, money was
      concurrently available under an RR4 schedule. As the number of free cigarettes
      increased, fewer responses were made for cigarettes and fewer cigarettes were
      earned. A behavioral economic analysis of cigarette demand curves revealed that
      demand for cigarettes was equally elastic when subjects received 5 or 10 free
      cigarettes, but less elastic when they received no free cigarettes. We conclude
      that whether an economy is closed or open affects drug (cigarette) consumption in
      humans, but the degree of openness has limited effects.

PMID- 11224265
TI  - Methylatropine blocks the central effects of cholinergic antagonists.
AB  - These studies were conducted in order to establish the dose dependency and
      relative peripheral versus central activity of four prototypical cholinergic
      antagonists on the rodent passive avoidance response, a widely used animal model
      of retention. Subcutaneous administration of 0.1 to 100mg/kg revealed a potency
      profile of scopolamine > atropine methylscopolamine >/= methylatropine for the
      impairment of passive avoidance responding. A series of neurological assessments
      of the doses used indicated that side effects alone were not sufficient to impair
      passive avoidance responding. Although inactive when delivered peripherally,
      methylatropine was able to produce retention deficits at 10nmol (3.66ug) when
      administered intracerebrally. To further evaluate whether systemic methylatropine
      could enter the central nervous system, either scopolamine or atropine was
      administered subcutaneously in mice and rats pretreated with 10-100mg/kg
      methylatropine. The deficit-producing effects of scopolamine and atropine were
      abolished with methylatropine. Thus methylatropine is an exclusive peripheral
      antagonist; its ability to block the deficit-producing effects of scopolamine and
      atropine may occur through a change in blood-brain barrier permeability or
      through uncharacterized pharmacokinetic properties.

PMID- 11224266
TI  - Discriminative-stimulus effects of azaspirodecanedione anxiolytics in baboons
      trained to discriminate beta-carboline-3-carboxylic acid ethyl ester or
      pentylenetetrazole.
AB  - Baboons were trained to discriminate either pentylenetetrazole (PTZ) or beta
      carboline-3-carboxylic acid ethyl ester (beta-CCE) from the no-drug condition.
      Both drugs specifically bind sites in the gamma-aminobutyric acid A (GABA(A))
      receptor complex and decrease GABAergic transmission. beta-CCE occasioned drug
      lever responding in baboons trained to discriminate PTZ and vice versa.
      Flumazenil, the benzodiazephine receptor antagonist, blocked beta-CCE, consistent
      with beta-CCE's receptor binding activity. The azaspirodecanedione anxiolytics
      buspirone and ipsapirone produced full generalization in all baboons; gepirone
      and tandospirone yielded full generalization in some baboons and partial in
      others. These anxiolytics are inactive in the GABA(A) complex and potently bind 5
      HT(1A) sites. A specific 5-HT(1A) ligand, 8-hydroxy-2-(di-n-propylamino)tetralin,
      produced generalization similar to gepirone and tandospirone, which show the most
      specific 5-HT(1A) binding. The major azaspirodecanedione metabolite, 1-(2
      pyrimidinyl)piperazine (an alpha(2)-adrenergic antagonist), occasioned the least
      drug-appropriate responding. Full generalization to buspirone and ipsapirone may
      have resulted from dopaminergic or alpha(1)-adrenergic activity combined with 5
      HT(1A) activity. The molecular mechanism of the generalization profile for PTZ
      and beta-CCE shown by the present results is unclear. The data may reflect
      altered relationships between GABAergic and serotonergic transmission, and
      altered stimulus effects of the training drugs, in the context of chronically
      decreased GABAergic transmission.

PMID- 11224267
TI  - Opioid pharmacology of the antinociceptive effects of loperamide in mice.
AB  - Loperamide (0.1-3.2mg/kg i.p.) produced dose-dependent and complete suppression
      of writhing in the acetic acid-induced writhing assay in mice. Naltrexone (NTX;
      0.1-10.0mg/kg s.c.) and its N-methylated derivative quaternary naltrexone (QNTX;
      1.0 and 10.0mg/kg s.c.) were roughly equipotent in antagonizing the
      antinociceptive effects of loperamide. In contrast, NTX was approximately 100
      fold more potent than QNTX in antagonizing the antinociceptive effects of the
      classical mu agonist morphine. Furthermore, the antinociceptive effects of
      loperamide were not antagonized by central administration of the selective mu
      antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP; 300ng i.c.v.), or by
      systemic administration of either the kappa selective antagonist nor
      binaltorphimine (nor-BNI; 32.0mg/kg s.c.), or the delta antagonist naltrindole
      (NTI; 10.0mg/kg s.c.). These doses of CTAP, nor-BNI and NTI were effective
      antagonists of morphine, the kappa agonist U69,593 and the delta agonist BW
      373U86 [(+/-)-4-((R*)-a-((2S*5R*)-4-allyl-2,5-dimethyl-1- piperazinal)-3
      hydroxybenzyl)-N, N-diethylbenzamide dihydrochloride], respectively. These
      results indicate that the antinociceptive effects of loperamide in mice are
      mediated, at least in part, by opioid receptors; however, these receptors are
      distinct from the opioid receptors mediating the effects of morphine, U69,593 and
      BW 373U86. These results are consistent with the hypothesis that loperamide
      produces its antinociceptive effects by acting, at least in part, at peripheral
      opioid receptors.

PMID- 11224268
TI  - Effects of olanzapine and other antipsychotic agents on responding maintained by
      a conflict schedule.
AB  - The effects of the "atypical" antipsychotic olanzapine and several other
      antipsychotics were examined using a conflict schedule. Rats were trained to
      respond for food on a three-component schedule, comprising variable-interval 30s
      (food, VI30) and fixed-ratio 10s (food + shock, FR10) components separated by
      time-out (TO). Olanzapine (0.3125-1.25mg/kg), clozapine (1.25-5mg/kg) and
      chlordiazepoxide (2.5-5mg/kg) decreased or had no effect on VI30 responding,
      whereas responding in the FR10 component increased. Chlordiazepoxide (5mg/kg)
      also increased TO responding. The antipsychotic agents haloperidol (0.125 and
      0.25mg/kg), trifluoperazine (0.0625-0.25mg/kg), remoxipride (1.25-5mg/kg) and
      risperidone (0.0625-0.5mg/kg) decreased V130 responding and either had no effect,
      or decreased TO and FR10 rates. The anticholinergic agent scopolamine (0.03125
      0.25mg/kg) decreased VI30 responding. The 5-HT(2) antagonist ritanserin (2.5 and
      5mg/kg) and the anticholinergic agent trihexyphenidyl (2.5 and 5mg/kg) had no
      effect on responding. Flumezanil (10mg/kg) reduced the anticonflict effect of
      chlordiazepoxide but not olanzapine. These results further emphasize the unusual
      profile of olanzapine.

PMID- 11224269
TI  - Catalase inhibition attenuates the acquisition of ethanol and saccharin-quinine
      consumption in laboratory rats.
AB  - Several lines of evidence suggest that the enzyme catalase plays an important
      role in many of the behavioral and reinforcing effects of ethanol, through its
      putative role in the central production of acetaldehyde. The role of catalase in
      the acquisition of voluntary ethanol consumption was examined in the present
      experiments by administering the catalase inhibitor 3-amino-1,2,4-triazole
      (aminotriazole) during the presentation of an ascending series of concentrations
      of either ethanol or saccharin-quinine solutions. Aminotriazole (0.5g/kg)
      significantly attenuated consumption of both ethanol and saccharin-quinine
      solutions throughout the acquisition period, and this effect remained during a
      subsequent maintenance period during which no injections were administered.
      Drinking did recover, however, when the acquisition procedure was reinstated.
      These results suggest that the effect of aminotriazole on the consumption of
      ethanol and saccharin-quinine may be the result of a change in reactivity to
      taste, or an aversive effect caused by drug administration.

PMID- 11224270
TI  - A-68930, a novel, potent dopamine D1 receptor agonist: a microstructural analysis
      of its effects on feeding and other behaviour in the rat.
AB  - A-68930 [1R, 3S)-1-aminomethyl-5,6-dihydroxy-3-phenylisochroman HCI] is a novel,
      potent and selective dopamine D1 receptor agonist. Previous reports have shown
      that the selective D1 partial agonist, SK & F 38393, reduced food consumption in
      rats and mice. The aim of this study was to undertake a microstructural analysis
      of the effects of A-68930 on food intake and feeding behaviour in non-deprived
      male rats trained to consume a highly palatable diet in a 20min period. A-68930
      (0.1-1.0mg/kg, s.c.) produced a dose-dependent reduction in food intake which was
      due to a reduction in the frequency of bouts of feeding but not to a reduction in
      bout duration. A-68930 had little effect on the latency to initiate feeding or on
      the local rate of eating. Hence, it had a selective action on the parameters of
      eating, which is distinctly different from the effects of selective D2 agonists
      or of indirectly acting psychomotor stimulants like cocaine. A-68930 also
      increased grooming by lengthening the grooming bouts, and reduced locomotion and
      rearing responses. At the largest dose, immobility was increased. The anorectic
      effect of A-68930 may reflect, at least in part, the increased grooming it
      produces.

PMID- 11224271
TI  - Failure of Delta(9)-tetrahydrocannabinol and CP 55,940 to maintain intravenous
      self-administration under a fixed-interval schedule in rhesus monkeys.
AB  - The lack of procedures which can unequivocally demonstrate cannabinoid self
      administration in animals has been an obstacle to the study of the neural basis
      for the reinforcing effects of this drug class. Because delta(9)
      tetrahydrocannabinol (delta(9)-THC) produce a relatively slow-onset, long-lasting
      behavioral effect, a self-administration procedure with widely spaced drug
      deliveries was evaluated as an alternative to fixed-ratio schedules which
      typically require frequent, closely spaced injections to demonstrate reinforcing
      effects. Three adult male rhesus monkeys were surgically implanted with
      intravenous catheters and trained to self-administer phencyclidine (PCP) under a
      10min fixed-interval schedule of reinforcement. Three injections were available
      each day, separated by 2h periods during which responding had no programmed
      consequences. In an attempt to link the effect of the drug with the response
      which produced it, each 20s injection was paired with a red light which remained
      illuminated for 10min. PCP (100ug/kg/injection) maintained steady rates of
      responding during each availability period, ranging from approximately 0.2 to 0.7
      responses/s. During 7 day substitution periods, Delta(9)-THC (17
      100ug/kg/injection) maintained low rates of responding which occasionally
      surpassed those during vehicle substitutions, but fell far below rates maintained
      by PCP. Substitution tests with the potent Delta(9)-THC analog CP 55,940 also
      resulted in low rates of responding. These results demonstrate that Delta(9)-THC
      is a poor reinforcer in animals, even under conditions where some of its
      unfavourable biodispositional properties are taken into consideration.

PMID- 11224272
TI  - Caffeine reinforcement demonstrated in a majority of moderate caffeine users.
AB  - A mutually exclusive choice procedure was used to evaluate the reinforcing
      effects of caffeine in eleven normal subjects with histories of regular caffeine
      consumption (mean 256mg/day). Subjects participated for 24 weeks; each week
      consisted of three consecutive daily sessions (two sampling days followed by a
      choice day) during which subjects were required to abstain from dietary sources
      of caffeine. On each sampling day subjects ingested four capsules, one every 2h.
      Capsules contained placebo on one sampling day and caffeine (50 or 100mg/capsule)
      on the other sampling day. Placebo and caffeine were associated with different
      color-coded capsules. At the beginning of the choice day subjects chose one of
      the two color-coded capsules they wished to take on that day; they were required
      to ingest one capsule and, thereafter, they could ingest up to six additional
      capsules of the same color throughout the day. Across subjects and dose, caffeine
      was chosen over placebo on 80% of choice occasions; nine of 11 subjects (82%)
      chose caffeine on more than 70% of choice occasions and caffeine choice was
      replicable despite changes in capsule colors across blocks. This is the first
      study in a relatively uncontrolled outpatient context to demonstrate significant
      caffeine reinforcement in the majority of normal subjects.

PMID- 11224273
TI  - Effects of excitatory amino acid antagonists on social recognition of male rats.
AB  - The effects of NMDA and non-NMDA glutamate receptor antagonists were evaluated on
      social recognition of adult male rats. Adult animals were injected (s.c.) with
      drug or saline immediately after the initial exposure to a juvenile male, 21-24
      days old, and re-exposed to the same or to a novel juvenile 30min later. If the
      time spent by animals in social investigation during re-exposure to the same
      juvenile was comparable with the time measured during the initial exposure and
      with the time of animals re-exposed to a novel juvenile, the effect of a drug was
      designated as amnesia. Such an effect was found in adult animals administered 1
      and 1.5mg/kg phencyclidine, 0.1mg/kg dizoclipine, 2.5mg/kg CPP, and 4mg/kg CGS
      19755. Amnesic effects were observed at doses not affecting motor performance. No
      amnesic effect was produced by CNQX and NBQX (2.5, 5 and 10mg/kg). These results
      show that while recognition capacity in adult male rats is disrupted by several
      NMDA antagonists, non-NMDA antagonists do not interfere with short-term retention
      of individual odours. This suggests that NMDA glutamate receptors may be involved
      in the processing of socially relevant olfactory information.

PMID- 11224274
TI  - Acute behavioral effects of lorazepam and caffeine, alone and in combination, in
      humans.
AB  - The widespread use of benzodiazepines and caffeine makes their combined use
      inevitable. The purpose of the present experiment was to assess the acute effects
      of lorazepam (0,2.8 and 5.6mg/70kg) and caffeine (0, 250 and 500mg/70kg), alone
      and in combination, on human learning, performance and self-reports. Subjects
      were nine healthy, male volunteers. Subjects received all possible combinations
      according to a Latin Square design. Lorazepam administered alone dose-dependently
      disrupted learning and performance on the Repeated Acquisition and Performance
      procedure and Digit Symbol Substitution Test (DSST), and increased subject
      ratings of sedation. Caffeine administered alone did not affect learning,
      performance or subject ratings to a statistically significant degree. Caffeine
      attenuated lorazepam-induced decrements in learning and performance on the
      Repeated Acquisition and Performance procedure and DSST. Consistent with the
      learning and performance measures, caffeine offset lorazepam-induced increases in
      subject ratings of sedation. These results demonstrate that caffeine generally
      attenuates the behavioral and self-reported effects of lorazepam on a variety of
      performance measures. An important extension of these findings would be to test
      the combined effects of lorazepam and caffeine in other behavioral paradigms such
      as drug self-administration.

PMID- 11224275
TI  - Serotonin involvement in the discriminative stimulus effects of mu and kappa
      opioids in rats.
AB  - The role of serotonin (5-HT) in the discriminative stimulus effects of opioids
      was examined using a two-lever, food-reinforced drug discrimination procedure.
      The effects of the 5-HT(1A) full agonist 8-OH-DPAT, the 5-HT(1A) partial agonist
      buspirone and the 5-HT(2) antagonist ketanserin were evaluated in rats trained to
      discriminate the mu opioid agonist morphine, or the kappa opioid agonist U50, 488
      from saline. In rats trained to discriminate 5.6mg/kg of morphine from saline,
      morphine dose-dependently substituted (produced >/= 80% morphine-appropriate
      responding) for the morphine stimulus. In contrast, U50,488, 8-OH-DPAT and
      ketanserin did not substitute for morphine, and buspirone produced only a small
      degree of substitution (approx. 40% morphine-appropriate responding). When
      administered in combination with morphine, 8-OH-DPAT, but not buspirone and
      ketanserin, attenuated the discriminative stimulus effects of higher doses of
      morphine. In rats trained to discriminate 5.6mg/kg of U50, 488 from saline, U50,
      488 dose-dependently substituted for the U50, 488 stimulus. When administered
      alone, 8-OH-DPAT and buspirone partially substituted (produced between 40% and
      79% U50, 488-appropriate responding) for the U50,488 stimulus, whereas morphine
      and ketanserin did not substitute for U50,488. The opioid antagonist naltrexone
      failed to antagonize the effects of 8-OH-DPAT and buspirone suggesting that the
      effects of these drugs in U50,488-trained rats were not mediated by opioid
      receptors. When administered in combination with U50,488, 8-OH-DPAT, but not
      buspirone or ketanserin, attenuated the discriminative stimulus effects of the
      training dose of U50,488. These results suggest that the 5-HT system is involved
      in the discriminative stimulus effects of both morphine and U50,488, although the
      exact nature of this 5-HT involvement is not clear.

PMID- 11224277
TI  - Reinforcing and subjective effects of methylphenidate in humans.
AB  - This study assessed the reinforcing and subjective effects of methylphenidate in
      a group of 35 adults (15 females and 20 males) with no history of drug
      dependence. A discrete-trial choice procedure was used to assess the reinforcing
      effects of a single oral dose of methylphenidate selected to produce a moderate
      subjective response in each subject (range 20-40mg). A number of variables
      (gender, current and past drug use, personality, and baseline mood and arousal)
      were examined in an attempt to identify sources of variability in drug response.
      Methylphenidate was chosen on 28% of occasions. In the group as a whole,
      methylphenidate had no effect on ratings of drug liking, but did increase ratings
      indicative of "positive" mood, CNS stimulation and anxiety. Within-subject
      variability in methylphenidate choice was related to variability in subjective
      response to the drug across choice trials. Methylphenidate choice was also
      associated with between-subject differences in prior opioid use and several
      personality dimensions. When compared with the results of a prior study of the
      same design with d-amphetamine, these results suggest that methylphenidate
      produces a somewhat different profile of subjective effects, and may be a less
      efficacious reinforcer than d-amphetamine.

PMID- 11224276
TI  - Interactions between the effects of propranolol and nicotine on radial maze
      performance of rats with lesions of the forebrain cholinergic projection system.
AB  - This experiment investigated the hypothesis that nicotine-induced regional
      release of noradrenaline contributes to the improvements in radial maze
      performance following nicotine treatment in rats with lesions to the forebrain
      cholinergic projection system (FCPS), by examining whether pretreatment with the
      noradrenergic beta-receptor antagonist propranolol abolished the facilitative
      effects of nicotine. After S-AMPA (8.0mM) lesions to the nuclei of origin of the
      FCPS in the nucleus basalis and medial septal areas, rats displayed long-lasting
      impairment in long-term reference and short-term working memory in both spatial
      (place) and associative (cue) radial maze tasks. Performance of control and
      lesioned rats was assessed after administration of nicotine (0.1mg/kg),
      propranolol (either 0.5 or 5.0mg/kg) and both treatments. Nicotine reduced
      working memory error rates in lesioned animals, but did not affect the
      performance of controls. Propranolol dose-relatedly increased error rates in both
      control and lesioned animals. Adverse effects were more marked in controls, all
      four types of error being increased under the high dose of propranolol, whereas
      in lesioned rats significant increases in error rates above baseline were
      confined to working memory. The low dose of propranolol, in conjunction with
      nicotine, abolished the improvement in working memory seen with nicotine alone in
      lesioned rats. However, under joint treatment with the high dose, the substantial
      increases in working memory error rates seen in lesioned rats after propranolol
      alone were reduced to baseline level. In controls, reduction in errors to
      baseline was seen only in the cue task; place task errors remained significantly
      elevated. These results suggest that both cholinergic depletion and noradrenergic
      blockade exert disruptive effects on cognition, but that these effects are
      largely independent, since an additive or interactive mechanism would be
      predicted to produce greater disruption, following noradrenergic blockade, in
      lesioned rather than in control animals. Although facilitative effects of
      nicotine were abolished with the low dose of propranolol, the results further
      suggest that these effects are independent of release of noradrenaline, since
      nicotine continued to reduce errors in control and lesioned animals following
      blockade of beta receptors with the high dose of propranolol.

PMID- 11224278
TI  - Transient hypersensitivity to apomorphine-induced gnawing after termination of
      acute effects of a single high dose of cocaine.
AB  - Physical dependence on cocaine has not been fully characterized or definitively
      identified. Since behavioral changes are typically not observed after cocaine
      withdrawal in animal studies, we sought to amplify or reveal any such changes in
      behavior by administration of the dopamine agonist apomorphine. C57BL/6J mice
      were tested for behavioral effects (climbing, gnawing, and locomotor activity) of
      apomorphine at various times after acute administration of cocaine. When tested
      at a time when most of the administered cocaine had disappeared from brain and
      when behavioral effects of cocaine had dissipated, at 2 and 4h post cocaine
      administration, effects of apomorphine on gnawing were increased 4-fold. This
      dopaminergic hypersensitivity was induced by acute treatment with doses of
      15mg/kg cocaine and higher. Effects of apomorphine were not enhanced at later
      time periods (6 to 24h after cocaine), indicating a rapid waning of the
      dopaminergic hypersensitivity. Hypersensitivity to apomorphine was not further
      augmented by 8 days of daily cocaine injections. Cocaine did not influence
      climbing and hypomotility induced by apomorphine 4h after its injection,
      demonstrating selectivity in the behavioral expression of the dopaminergic
      hypersensitivity. Further, cocaine did not induce sensitization to its own
      effects indicating that the hypersensitivity to apomorphine was not due to a
      typical sensitization phenomenon. The results of these experiments demonstrate a
      short-lived dopaminergic supersensitivity after termination of the acute effects
      of a single high dose of cocaine, the implications of which remain to be
      discovered.

PMID- 11224279
TI  - Social interaction increases 5-HT release and cAMP efflux in the rat ventral
      hippocampus in vivo.
AB  - The aim of the present study was to combine in vivo microdialysis in the rat with
      behaviour in the social interaction test in order to investigate changes in both
      5-HT release and cyclic AMP (cAMP) efflux in the ventral hippocampus with
      simultaneous measurement of behaviour. Exposure of the rat to a 10min period of
      social interaction with an unfamiliar partner in a brightly lit, unfamiliar arena
      resulted in an increase in extracellular 5-HT and extracellular cAMP in the
      ventral hippocampus. Pretreatment with diazepam (1mg/kg i.p.) 30min prior to the
      social interaction test significantly inhibited the increases in both
      extracellular 5-HT and cAMP while significantly increasing the amount of time the
      pair of rats spent in active social contact over the 10min period. During the
      30min prior to the social interaction test diazepam reduced basal levels of 5-HT,
      but had no effect on the basal efflux of cAMP. Pretreatment with a selective 5
      HT(1A) antagonist, WAY 100135 (5mg/kg s.c.), 30min the social interaction test,
      significantly potentiated the increase in extracellular 5-HT observed in saline
      treated rats during the social interaction test. In contrast, WAY 100135
      pretreatment significantly attenuated the increase in extracellular cAMP observed
      in saline-treated rats during the social interaction test but had no effect on
      the time spent in active social contact between pairs of rats. The results
      suggest that social interaction results in activation of a post-synaptic 5-HT
      receptor (5-HT(1A) or 5-HT(6)/5-HT(7)) coupled to adenylate cyclase but that this
      receptor is not responsible for the aversion-induced behaviour. Furthermore
      antagonism of the 5-HT(1A) somatodendritic autoreceptor under conditions of 5-HT
      neuronal activation, but not under basal conditions, potentiates 5-HT release.

PMID- 11224280
TI  - The effects of chronic administration of ceronapril on the partial reinforcement
      extinction effect and latent inhibition in rats.
AB  - Previous experiments showed that acute administration of the angiotensin
      converting enzyme (ACE) inhibitor, ceronapril, shares with neuroleptic drugs an
      ability to enhance latent inhibition (LI), which consists of retardation in
      conditioning to a stimulus as a consequence of its prior non-reinforced pre
      exposure. Experiment 1 tested whether ceronapril would produce a neuroleptic-like
      effect in the partial reinforcement extinction effect (PREE) at one trial a day.
      The PREE refers to the increased resistance to extinction observed in animals
      trained on a partial reinforcement (PRF) schedule compared with those trained on
      a schedule of continuous reinforcement (CRF). Two groups of rats were trained to
      run in a straight alley. The CRF group received food reward on every trial. The
      PRF group was rewarded on a quasi-random 50% schedule. All animals were then
      tested in extinction in which no reward was given. Ceronapril at a dose of
      0.05mg/kg was administered in a 2 x 2 design, with drug or no drug in acquisition
      and drug or no drug in extinction. Rats receiving vehicle in acquisition showed a
      PREE, regardless of their drug treatment in extinction. In contrast, ceronapril
      administered in acquisition attenuated the PREE irrespective of drug treatment in
      extinction, by both increasing resistance to extinction in CRF animals and
      decreasing resistance to extinction in PRF animals. This pattern of results does
      not resemble that produced by neuroleptics. The PREE procedure necessitated
      repeated administration of ceronapril whereas the previous demonstrations of
      neuroleptic-like enhancement of LI have been obtained with acute administration.
      Experiment 2 therefore tested the effects of chronic ceronapril administration on
      LI. Under these conditions, ceronapril abolished LI. The results are discussed in
      relation to the antipsychotic, anti-anxiety and cognitive-enhancing effects
      formerly attributed to ACE inhibitors.

PMID- 11224281
TI  - Triazolam discrimination by humans under a novel response procedure: effects of
      buspirone and lorazepam.
AB  - Six healthy human volunteers (ages 18 to 24) acquired a triazolam (0.32mg/70kg)
      vs placebo discrimination under a standard, two-response drug discrimination
      procedure. Dose-effect curves were then determined for triazolam (0.1
      0.56mg/70kg), lorazepam (0.75-3.0mg/70kg) and buspirone (7.5-30mg/70kg) under a
      novel response procedure that provided a response alternative for drugs unlike
      triazolam or placebo (i.e. a novel-appropriate response). Triazolam dose
      dependently increased triazolam-appropriate responding but did not occasion any
      novel-appropriate responding. Lorazepam dose-dependently increased triazolam
      appropriate responding in four of six subjects, but at least one dose also
      occasioned novel-appropriate responding in three subjects. Buspirone dose
      dependently increased novel-appropriate responding, although three of six
      subjects also made triazolam-appropriate responses following some dose(s). All
      three drugs comparably increased self-reported sedation. Self-reported effects
      did not differentiate triazolam from lorazepam whereas only buspirone increased
      "bad" self-reports, and did not increase "liking" and "good" self-reports. The
      results suggest that the novel response procedure enhanced the pharmacological
      selectivity of human benzodiazepine discrimination and may help interpret partial
      generalization under two-choice drug discrimination procedures. The results also
      add to the evidence of a close relationship between the discriminative stimulus
      and self-reported effects of drugs.

PMID- 11224282
TI  - Effects of 8-OH-DPAT, 5-CT and muscimol on behaviour maintained by a DRL20
      schedule of reinforcement, following microinjection into the dorsal or median
      raphe nuclei.
AB  - Experiments were performed to investigate the effects of microinjections of the 5
      HT(1A) agonist 8- hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), the non
      selective 5-HT(1) agonist 5-carboxamidotryptamine (5-CT) and the GABA(A) agonist
      muscimol into the midbrain raphe nuclei, on behaviour maintained by a
      differential reinforcement of low rate (DRL) 20 schedule of food reinforcement.
      Following acquisition of responding under the DRL20 schedule, in which responses
      were reinforced only if they occurred at least 20s after the previous response,
      two groups of rats were prepared with a stainless steel guide cannula aimed at
      either the dorsal raphe nucleus or the median raphe nucleus. Injections of 8-OH
      DPAT and 5-CT into the median raphe dose-dependently increased responding and
      reduced the number of reinforcers earned, leading to a net reduction in response
      efficiency from 45% to approximately 27% (5ug 8-OH-DPAT) and 22% (375ng 5-CT).
      Both drugs appeared to shift the frequency distribution of inter-response times
      (IRTs) towards shorter IRTs, and lowered the mean IRT. These effects were not
      observed after dorsal raphe injections of either drug. This pattern of results,
      together with results obtained in other paradigms measuring response inhibition,
      suggests that suppression of the activity of median raphe 5-HT neurones induces
      deficits in the ability to withhold responding. Muscimol increased responding,
      decreased the number of reinforcers earned and reduced response efficiency after
      both dorsal raphe and median raphe injections. These effects were more pronounced
      following median raphe injections, and were of considerably greater magnitude
      than those observed following treatment with the 5-HT agonists. Muscimol injected
      into the median raphe lowered the mean IRT, and increased the frequency of short
      duration IRTs. Thus, stimulation of GABA(A) receptors within the median raphe
      induces a pattern of behavioural disruption in the DRL task, that is more severe
      than that resulting from selective inhibition of 5-HT neural activity. The
      effects of muscimol probably arise from a general behavioural activation, rather
      than a specific deficit in the ability to withhold responding.

PMID- 11224283
TI  - Effects of nicotine on cooperative responding among abstinent male smokers.
AB  - The effects of nicotine on human cooperative responding in abstinent male smokers
      were examined. During episodes occurring at random times through a session,
      concurrently available cooperative and independent responses were maintained by
      points exchangeable for money. Cooperative responses simultaneously added points
      to counters marked "Your Earnings" and "Other's Earnings" only if the subject's
      and another person's responses ostensibly coincided. Independent responses added
      points only to the counter marked "Your Earnings". After the first daily session
      abstinent subjects smoked ad libitum, received either 0, 2 or 4mg nicotine gum or
      abstained from smoking. Increases from this first session in time allocated to
      the cooperative response option, proportion of cooperative responses and
      cooperative response rate were significantly greater following ad libitum smoking
      or acute administration of 4mg nicotine. No effects of nicotine abstinence were
      observed on independent response rate. These results suggest effects on
      sociability may maintain nicotine use and increase relapse risk in abstinent
      smokers.

PMID- 11224284
TI  - Tolcapone: a potential new antidepressant detected in a novel animal model of
      depression.
AB  - The potential antidepressant properties of tolcapone, a new catechol-O-methyl
      transferase (COMT) inhibitor, were investigated in a novel animal model of
      depression. Chronic mild stress (CMS)-induced anhedonia in rats is recognized as
      a model of depression with predictive and etiological validity. Here, the effects
      of CMS on the hedonic state of animals were assessed using a self-stimulation
      paradigm in which rats self-activate the ventral tegmental area. Frequency
      thresholds for self-stimulation responses were determined prior to, during and
      after a 19 day period of exposure to a variety of intermittent, unpredictable,
      mild stressors. In vehicle-treated stressed animals, stimulation threshold was
      significantly increased after about 12 days, reflecting a gradual development of
      an "anhedonic" state. This anhedonia persisted throughout the stress period and
      subsequently disappeared over a 10 day period. This stress-induced anhedonic
      state was not observed in stressed rats concomitantly treated with tolcapone (10
      or 30mg/kg b.i.d.). In non-stressed vehicle- or drug-treated animals, no
      significant change in self-stimulation threshold was consistently observed. These
      results suggest that selective, reversible COMT inhibitors such as tolcapone may
      offer an innovative approach to the treatment of depression, in addition to their
      potential therapeutic use in Parkinson's disease.

PMID- 11224285
TI  - Antagonism of a nicotine plus midazolam discriminative cue in rats.
AB  - Rats were trained to discriminate nicotine (0.4mg/kg s.c.), midazolam (0.2mg/kg
      s.c.) or the combination of these drugs from saline (n = 10). The rats were
      trained to 95% accuracy in a two-bar operant procedure with a tandem schedule of
      food reinforcement. Testing with the individual drugs in the mixture-trained
      group showed that nicotine (85% drug-appropriate responding) was a more salient
      component than midazolam (47%) in the compound stimulus. The rats were tested
      with benzodiazepine and nicotine antagonists individually and in combination
      (mecamylamine 0.2-1.6mg/kg s.c.; flumazenil 2.5-20mg/kg i.p.). Results for the
      mixture-trained animals showed that flumazenil had no effect on its own, however
      mecamylamine on its own produced a significant but incomplete block in doses of
      0.4-1.6mg/kg. The greater salience of the nicotine component of the cue would
      explain the block by mecamylamine but not flumazenil. The antagonists in
      combination produced greater blockade than mecamylamine on its own. The
      selectivity of the antagonist actions on the different cue components was also
      demonstrated. The results suggest that in drug discrimination experiments, "false
      negative" results may be obtained with antagonists when a training drug produces
      a stimulus with more than one component.

PMID- 11224286
TI  - Memory of inhibitory avoidance in the rat is regulated by glutamate metabotropic
      receptors in the hippocampus.
AB  - This experiment investigated the effect on memory, in rats, of the bilateral
      intrahippocampal post-training infusion of the glutamate metabotropic receptor
      (mGLUR) agonist, ACPD (1S, 2R-aminocyclopentane dicarboxylate) and of the mGLUR
      antagonist, MCPG ([RS]-alpha-methyl-4-carboxyphenyl glycine). Male Wistar rats
      were implanted bilaterally with cannulae in the CA1 region of the dorsal
      hippocampus. After recovery from surgery they were trained in a step-down
      inhibitory avoidance task and tested for retention 24h later. Immediately or
      180min after training they received a bilateral intrahippocampal infusion of
      saline (0.5ul), ACPD (1.0 or 2.5ug/side), MCPG (2.5ug/side) or ACPD plus MCPG, in
      0.5ul saline. Upon immediate post-training infusion, ACPD caused a dose-dependent
      enhancement of memory and MCPG was amnestic. The effect of MCPG was antagonized
      by the simultaneous administration of ACPD. When given 180min after training, the
      drugs had no effect on memory. The results indicate that the early phase of
      memory is regulated by mGLURs in the hippocampus, and support the suggestion that
      memory involves long-term potentiation initiated at the time of training in the
      hippocampus.

PMID- 11224287
TI  - Reinstatement of heroin-reinforced behavior following long-term extinction:
      implications for the treatment of relapse to drug taking.
AB  - The effect of non-contingent priming injections of heroin on drug-reinforced
      behavior following long-term extinction was examined. Male rats were trained to
      lever press for 100ug/kg/infusion of intravenous heroin during four 6h sessions
      per day. The drug-reinforced behavior was extinguished by daily reductions in
      dose followed by at least 12 sessions of saline self-administration. A single non
      contingent priming injection of heroin (100ug/kg, i.v.) resulted in the
      reinstatement of the drug-reinforced behavior, even though extinction conditions
      remained. The results indicate that the drug-induced reinstatement of previously
      extinguished drug-reinforced behavior is possible even after long periods of
      extinction. The implications of the present findings for the treatment of relapse
      to drug abuse in humans are discussed.

PMID- 11224288
TI  - Felbamate, a novel antiepileptic agent, does not affect cognition in rodents.
AB  - Felbamate is a novel anticonvulsant agent recently approved by the FDA for
      treatment of epilepsy in the US. While the mechanism of action of felbamate has
      not been fully eludicated, recent evidence has accumulated to suggest that
      felbamate may act at the strychnine-insensitive glycine binding site on the NMDA
      receptor complex. Since this receptor has been strongly implicated in cognitive
      processes, the current study was designed to investigate the potential effects of
      felbamate on learning performance. Doses of felbamate up to 1000mg/kg,
      administered subcutaneously (s.c.), did not produce deleterious effects on
      performance in either mice or rats, using a passive avoidance task. In contrast,
      the non-competitive NMDA antagonist dizocilpine produced performance deficits at
      doses from 0.1 to 1.0mg/kg s.c. in both rats and mice. Felbamate and dizocilpine
      prevented NMDA-induced convulsions with ED(50)s of 20.3 and 0.82mg/kg s.c.,
      respectively. Calculations for the therapeutic index (ratio of the deficit
      producing to anticonvulsant doses) for dizocilpine resulted in less than a 1-fold
      separation in dose, while the therapeutic index for felbamate was greater than
      50. Taken together, these results indicate that felbamate does not produce
      cognitive deficits at doses more than 50 times the dose needed to block seizure
      activity in animals.

PMID- 11224290
TI  - Behavioural Pharmacology of Alcohol.

PMID- 11224289
TI  - Conditioned place aversion produced by microinjections of substance P into the
      periaqueductal gray of rats.
AB  - The dorsal periaqueductal gray (DPAG) is one of the main structures involved in
      the integration of defensive behavior in the brain. In order to investigate the
      participation of neuropeptides in the generation of aversive states,
      semicarbazide, a glutamic acid decarboxylase inhibitor, and substance P, an
      active neuropeptide, were injected into the DPAG and their effects evaluated in
      the open field and the place conditioning tests. While semicarbazide and
      substance P both increased locomotor activity only substance P increased grooming
      in the open field. In the place conditioning procedure similar aversion
      conditioning was produced by both drugs. These results confirm previous data
      showing that semicarbazide in the DPAG causes place aversion through reduction of
      tonic inhibitory mechanisms on neural substrates of aversion. Such mechanisms may
      include substance P neurons as substance P microinjection into the DPAG also
      functioned as an unconditioned stimulus in the place aversion test.

PMID- 11224291
TI  - Emerging neurochemical concepts in the actions of ethanol at ligand-gated ion
      channels.
AB  - Both data and opinion are beginning to unify a consensus concerning the
      neurochemical mediation of the effects of ethanol in the CNS. This review of the
      literature is offered as an introduction to the molecular and cellular aspects of
      the neurochemical effects of ethanol for behavioral pharmacologists. As such,
      this review emphasizes the receptor pharmacology of ethanol over its behavioral
      effects. The unifying principle throughout the review is that ethanol has
      selective effects at particular ionotropic receptors, including GABA(A), NMDA and
      5-HT(3) receptors. Current concepts of how ethanol may selectively interact with
      these receptor systems are discussed. In particular, the molecular
      characterizations of these receptors are reviewed to provide a foundation for
      understanding the differential interaction of ethanol with particular receptor
      subtypes and integrating data addressing the behavioral actions of ethanol.
      Extension of the neurochemical effects to behavioral outcomes is explored
      primarily via drug discrimination procedures. The recent advances that are
      highlighted include the receptor basis for regional sensitivity to ethanol and
      potential interactions of ethanol-induced neurochemical activity associated with
      alcohol intoxication. The integration and understanding of how multiple receptor
      systems interact to influence a behavioral outcome will remain an important
      challenge for behavioral pharmacologists interested in the effects of ethanol.

PMID- 11224292
TI  - Ionotropic receptors and stimulus effects of drugs: whisky and water or vodka on
      the rocks? Commentary on Grant, "Emerging neurochemical in the action of ethanol
      at ligand-gated ion channels"

PMID- 11224293
TI  - Neuropharmacological characteristics of individual differences in alcohol effects
      on aggression in rodents and primates.
AB  - Many violent crimes have been associated with alcohol intoxication, but
      experimental research in laboratory animals has been largely inconclusive on
      alcohol effects on aggression. A focus on individual differences rather than
      group statistics has revealed that low doses of ethanol cause large and
      repeatable increases in aggressive behavior in subgroups of rodents and primates.
      The recent progress using in vivo neuropharmacological techniques makes it
      feasible to explore differences in brain mechanisms in animals that show enhanced
      aggression after ethanol vs those that do not. Effects of ethanol on three major
      neurotransmitter systems (i.e. GABA, serotonin, dopamine) are examined. Since
      these neurotransmitter substances are critically important in the neurobiology of
      various kinds of aggressive behavior in rodent and primate species, they are
      potential mechanisms by which ethanol alters aggressive behavior. Direct research
      on the relevance of the physiological interaction between ethanol and the GABA
      receptor suggests that at least some of the effects of alcohol on aggression
      involve the GABA(A)-benzodiazepine receptor complex. The role of serotonin (5-HT)
      will have to be newly defined in light of the findings that ethanol increases 5
      HT release in several forebrain areas, in a dose range that can stimulate
      aggressive behavior in a subgroup of individuals. Recent in vivo studies show
      that acute exposure to ethanol increases dopamine release in discrete dopamine
      terminal areas, and that the initiation and execution of aggressive and defensive
      behavior are also synchronized with increased dopamine activity in these brain
      regions.

PMID- 11224294
TI  - Neurotransmission, the individual and the alcohol/aggression link. Commentary on
      Miczek et al. "Neuropharmacological characteristics of individual differences in
      alcohol effects on aggression in rodents and primates"

PMID- 11224295
TI  - Ethanol as a reinforcer: a review of laboratory studies of non-human primates.
AB  - This article reviews studies of ethanol self-administration in non-human
      primates. Between approximately 1960 and 1980 research programs at three
      university medical centers (Michigan, Minnesota and Baylor) established that
      ethanol could function as a reinforcer when delivered either intravenously,
      intragastrically or orally. Variables such as session length, dose and
      intermittent reinforcement schedules were examined, and tolerance and
      physiological dependence on ethanol were also studied. Procedures used to
      establish abused drugs as reinforcers via the intravenous, intragastric and oral
      route are also effective in the particular case of ethanol. Under conditions of
      limited access (e.g. 3h per day), the variables that control behavior reinforced
      by ethanol are the same as those that govern behavior reinforced by other drugs.
      Moreover, the functional relations between these variables and ethanol-reinforced
      responding are similar to the functional relations between the same variables and
      other drug reinforcers. However, with continuous 24h access to ethanol,
      differences appear with respect to other sedative-hypnotic drugs. In contrast to
      these other drugs, intravenous ethanol use results in a suppression of food
      intake, weight loss, self-initiated abstinence, and often, death. When
      intravenous and oral ethanol self-administration are compared, two important
      differences emerge: the maximum intakes via the intravenous route exceed the
      maximum intakes via the oral route, and, perhaps surprisingly, the doses required
      to maintain responding are lower with the oral route. Studies since 1980 have
      increased the scope of ethanol reinforcement research and also corroborated and
      extended earlier findings. In summary, ethanol can function as an effective
      reinforcer for non-human primates.

PMID- 11224296
TI  - Ethanol drug discrimination in rats: substitution with GABA agonists and NMDA
      antagonists.
AB  - Both enhancement of GABAergic neurotransmission and antagonism of glutamatergic
      neurotransmission involving the NMDA receptor have been implicated in the acute
      effects of ethanol. In this study, rats were trained to discriminate 1000mg/kg
      ethanol from saline. This dose of ethanol was consistently discriminated from
      saline but had no effects on overall rates of responding. Substitution tests were
      conducted with a number of GABA agonists and NMDA antagonists. Both midazolam and
      pentobarbital exhibited substantial substitution for ethanol at doses that
      moderately decreased response rates. However, muscimol and baclofen completely
      failed to substitute for ethanol, as did a combination of a fixed dose of
      muscimol with increasing doses of baclofen. The non-competitive NMDA antagonists
      PCP, dizocilpine and ketamine substituted fully for ethanol, but only at doses
      that also substantially suppressed rates of responding. The competitive NMDA
      antagonists, CPPene and NPC 17742, partially substituted for ethanol. The levels
      of substitution for ethanol among the indirect GABA agonists and the non
      competitive NMDA antagonists indicate that the discriminative stimulus effects of
      ethanol, at least at a 1000mg/kg dose, may involve both GABAergic and
      glutamatergic systems.

PMID- 11224297
TI  - Discrimination of ethanol and of diazepam: differential cross-tolerance.
AB  - These experiments tested the hypothesis that cross-tolerance between ethanol
      (EtOH) and diazepam would occur in a drug discrimination paradigm. One group of
      rats (n = 28) was trained to discriminate EtOH (1.0g/kg, i.p.) from vehicle;
      another group of rats (n = 10) was trained to discriminate diazepam (5.6mg/kg,
      i.p.) from vehicle. Subjects were trained using a two-lever choice procedure
      where food was delivered under a fixed-ratio 10 schedule of reinforcement. In
      rats trained to detect EtOH, both EtOH (0.1-1.78g/kg) and diazepam (0.32-10mg/kg)
      dose dependently substituted for EtOH. Chronic administration of EtOH
      (6.8g/kg/12h for 7 days) resulted in 3-fold tolerance to EtOH and 6-fold cross
      tolerance to the ability of diazepam to substitute for EtOH; chronic
      administration of diazepam (20mg/kg/8h for 7 days) failed to confer cross
      tolerance to EtOH nor did it produce tolerance to the ability of diazepam to
      substitute for EtOH. In rats trained to detect diazepam, diazepam (0.56-10mg/kg)
      but not EtOH (0.1-1.78g/kg) substituted for diazepam. Chronic administration of
      diazepam (20mg/kg/8h for 7 days) produced 3-fold tolerance to diazepam; in
      contrast, chronic administration of EtOH (6.8g/kg/12h for 7 days) failed to
      confer cross-tolerance to diazepam. The dissociation of the cross-substitution
      and cross-tolerance patterns between EtOH and diazepam suggests that the
      population of benzodiazepine receptors that mediates substitution of diazepam for
      EtOH differs from the population of benzodiazepine receptors that mediates
      substitution of diazepam for diazepam.

PMID- 11224298
TI  - Effects of ondansetron pretreatment on acute responses to ethanol in social
      drinkers.
AB  - Laboratory animal and clinical studies suggest that the 5-HT(3) receptor subtype
      may mediate some of the CNS effects of ethanol. Two experiments were conducted to
      evaluate the effects of the 5-HT(3) receptor antagonist, ondansetron, on the
      acute responses of social drinkers to a moderate dose of ethanol. In Experiment
      1, two doses of ondansetron (0.15 and 0.30mg) or placebo were tested in
      combination with ethanol (0.5g/kg) or placebo. In Experiment 2, three higher
      doses of ondansetron (1.0, 3.0 and 10.0mg) or placebo were tested in combination
      with ethanol (0.5g/kg) or placebo. Sessions were conducted one or two evenings
      per week from 16.00h until 20.45h. Separate groups of subjects participated in
      the two placebo-controlled, double-blind experiments (Experiment 1: n = 13;
      Experiment 2: n = 6). The order of drug administration was counterbalanced across
      subjects. In each study, subjects were given an intravenous infusion of
      ondansetron and 5min later consumed an ethanol or placebo beverage. For 3h after
      the beverage was consumed, physiological, subjective effects and performance
      measures were taken at regular intervals. Across a wide range of doses, the
      effects of ondansetron alone did not differ significantly from placebo. Ethanol
      alone produced prototypic effects on several measures (e.g., increased ratings of
      "positive" subjective effects and impaired memory performance). Furthermore,
      ondansetron pretreatment did not modify physiological, subjective or performance
      effects of ethanol. These findings do not support the hypothesis that the 5
      HT(3), receptor/channel complex mediates the positive subjective effects, or any
      other subjective or performance effects, of ethanol.

PMID- 11224299
TI  - Dissociation of serotonergic regulation of anxiety and ethanol self
      administration: a study with mCPP.
AB  - Alcohol dependence frequently co-exists with anxiety disorders, although it is
      unclear how these disorders functionally or neurochemically relate. Central
      serotonergic dysfunction may be one common factor. The aim of this study was to
      compare the effects of the mixed 5-HT agonist m-chlorophenylpiperazine (mCPP) on
      both anxiety-related (hole board/plus maze) and ethanol self-administration
      (limited access procedure) behaviours in male Wistar rats. mCPP was selected
      because it is known to be anxiogenic in both animals and humans, and to induce
      "craving" in abstinent alcoholics. For comparative purposes pentylenetetrazole
      (PTZ), a non-serotonergic anxiogenic agent, was also examined. mCPP (0.3 and
      1.0mg/kg s.c.) decreased exploratory behaviour in both the hole board and plus
      maze, which is indicative of anxiogenesis. At comparable doses, mCPP reduced
      ethanol and water intake during a limited access procedure where rats were
      presented with both a 12% ethanol solution and water. mCPP-induced anxiogenesis
      was reversed by two antagonists, metergoline (5-HT(1/2) receptor antagonist) and
      ritanserin (5-HT(2A/2C) receptor antagonist). However, the effect of mCPP on
      ethanol was modified only by metergoline, which suggests that different 5-HT
      receptor subtypes are involved in regulating these behaviours. Furthermore, there
      was no evidence of tolerance to the anxiogenic effect of mCPP (0.3mg/kg)
      following chronic (8 days) treatment. However, tolerance developed to its effect
      on ethanol intake. Upon discontinuation ethanol intake increased (by 41%). In
      contrast, PTZ (15.0mg/kg i.p.) induced anxiogenesis in the plus maze and also
      increased ethanol intake on chronic administration. Since mCPP and PTZ had
      opposite effects on ethanol intake, the effect of mCPP may not be related to its
      anxiogenic properties but rather reflect its non-selective pharmacology. This non
      selectivity of mCPP makes it an unsatisfactory pharmacological tool with which to
      investigate the functional relationship between anxiety and alcohol dependence.

PMID- 11224300
TI  - alpha(2)-Adrenoceptor antagonists and propensity to take alcoholic beverages.
AB  - Rats were maintained on a daily regimen involving a 2h opportunity to take both
      water and a sweetened alcoholic beverage (12% ethanol, 0.25% saccharin). After 3
      weeks on this regimen, rats regularly take substantial amounts of alcohol. After
      stabilization, injections of alpha(2)-adrenergic antagonists were administered,
      15min before the opportunity to drink. Yohimbine and methoxyidazoxan dose
      relatedly decreased intake of alcoholic beverage and increased intake of water.
      In Experiment 2, a number of rats were taken off the daily regimen for 9 days,
      then returned to it. Across the first 12 days of the reinstated daily regimen,
      half the rats received placebo and half methoxyidazoxan. The group receiving
      placebo rapidly returned to taking large amounts of alcoholic beverage while the
      group receiving methoxyidazoxan did not. In Experiment 3, it was shown that a
      dose of methoxyidazoxan that decreased intakes of alcoholic beverage did not
      decrease intakes of other palatable beverages. In Experiment 4, it was shown that
      yohimbine persistently reduced intakes of alcoholic beverage with daily
      administration. These results indicate that alpha(2)-antagonists might be
      effective pharmaceutical adjuncts to other treatments for alcohol abuse and
      alcoholism.

PMID- 11224301
TI  - Calcium channel inhibitors attenuate consumption of ethanol, sucrose and
      saccharin solutions in rats.
AB  - Ca(2+) channel inhibitors suppress ethanol intake in various strains of alcohol
      preferring rats. To test whether that inhibitory effect involves interference
      with the caloric consequences of preferred fluids, we compared the effects of two
      dihydropyridines, nicardipine and isradipine, and diltiazem, a benzothiazepine
      Ca(2+) channel inhibitor, on intake of and preference for 10% ethanol (v/v),
      13.7% sucrose (w/v, isocaloric to 10% ethanol) and non-caloric 0.02% saccharin
      (w/v) solutions. All of these Ca(2+) channel inhibitors dose-dependently (1.25
      5umol/kg isradipine, 5-20umol/kg nicardipine, 10-40umol/kg diltiazem) inhibited
      ethanol intake in alcohol-preferring P rats. Nicardipine and isradipine, but not
      diltiazem, simultaneously increased water intake and attenuated preference for
      ethanol. No change in food pellet intake was found. Similar inhibition was
      observed with regard to sucrose and saccharin intake in Sprague-Dawley rats,
      although higher doses (> 10umol/kg) were required to achieve that effect. No
      significant changes in sucrose preference, as opposed to consumption, were
      observed with any drug, and only nicardipine at its highest dose (20umol/kg,
      b.i.d.) significantly (p < 0.05) decreased preference for saccharin. In
      conclusion, all three Ca(2+) channel inhibitors significantly suppress
      consumption of caloric solutions of ethanol and sucrose, as well as of non
      caloric saccharin solution. Although an accompanying decrease, in preference is
      evident only for alcohol, it appears that these effects may be related to
      decreased palatability of flavored fluids. However, the contribution of changes
      in ethanol- and sucrose-induced caloric satiety cannot be ruled out.

PMID- 11224302
TI  - Voluntary ethanol consumption in rats: the importance of the exposure paradigm in
      determining final intake outcome.
AB  - The present investigation examined two methods of ethanol presentation to
      laboratory rats that have been used to examine the mechanisms mediating voluntary
      ethanol intake in animals. Experiment I examined whether a restricted access
      procedure had any significant and meaningful relationship in individual animals
      to drinking behavior in an unrestricted 24h paradigm. An unselected strain of
      rats was given free access (unrestricted 24h free choice) to ethanol and water,
      and later exposed to a restricted 10min access to ethanol. A significant positive
      relationship between the absolute amount of ethanol consumed in the 24h access
      paradigm and the amount ingested by the same animals in the restricted access
      procedure was demonstrated. Experiment 2 examined the extent to which a forced
      choice preference testing procedure, commonly used in screening ethanol
      preferring P rats, was in and of itself sufficient to produce increased levels of
      ethanol consumption in unselected Long-Evans rats. Results indicated that
      subjects receiving only 4 days of forced exposure to 10% ethanol consumed, over
      the next eight ethanol presentations, levels of ethanol exceeding 5g/kg with a
      0.60 preference ratio. A microstructural analysis of the pattern of free choice
      ethanol intake following forced ethanol exposure (Experiment 3) revealed that
      rats consumed ethanol within short discrete bouts with the largest of these daily
      bouts consisting of approximately 4ml (0.75g/kg) of 10% ethanol. The amount
      consumed during the restricted access bout of Experiment 1 was seen to be within
      the range of the bouts recorded in Experiment 3. These results suggest that
      consumption of ethanol during the restricted access may simulate an individual
      bout of ethanol intake during non-restricted access. The results support the
      notion that many of the different ethanol drinking models used may have a common
      basis and that the assessment of the amount and pattern of intake across methods
      and strains may represent different but equally valid approaches to the study of
      the same underlying mechanisms.

PMID- 11224303
TI  - A schedule induction probe technique for evaluating abuse potential: comparison
      of ethanol, nicotine and caffeine, and caffeine-midazolam interaction.
AB  - Previous research has shown that under daily 3h sessions of food schedule-induced
      drug solution polydipsia (on a fixed-time 1min (FT 1min) schedule, session probes
      at greater FT values induced comparatively more ml/pellet drinking of solutions
      of drugs possessing abuse potential (ethanol, cocaine, midazolam) than of vehicle
      or other drug solutions. The present study extended these findings to nicotine
      and caffeine, drugs that usually do not function as reinforcers in i.v. self
      administration studies with animals, but are known to have reinforcing effects
      for humans. The positive effects for nicotine and caffeine did not depend upon
      prior overindulgence in ethanol. Results on the effects of chronic, presession
      s.c. doses of midazolam could not be interpreted as contributing to the abuse
      potential of caffeine, but had independent dipsogenic effects. The FT probe
      technique, as well as schedule-induced i.v. self-administration, are useful
      methods for discerning the abuse potential of agents which are usually not
      distinguished by i.v. self-administration methods.

PMID- 11224304
TI  - Ethanol-reinforced behavior in P, NP, HAD and LAD rats: differential genetic
      regulation of reinforcement and motivation.
AB  - Genetic differences exist in whether animals find ethanol or other drugs
      positively reinforcing. Through the use of P, NP, HAD and LAD rats, animals
      selectively bred for high (P, HAD) or low (NP, LAD) ethanol consumption in a two
      bottle choice procedure, the present results show that multiple factors
      determining ethanol consumption can be identified. Ethanol-preferring P rats
      consumed more ethanol across all conditions involving fixed ratio or progressive
      schedules than did non-preferring NP, preferring HAD or non-preferring LAD rats.
      In both non-preferring NP and preferring HAD rats, responding decreased similarly
      as fixed ratio size was increased. However, under a progressive ratio schedule,
      NP rats responded to higher break points than did HAD rats. In LAD rats, ethanol
      has not consistently been shown to be a reinforcer and these rats exhibited the
      lowest levels of responding for ethanol across all conditions. These findings
      extend the conditions under which P rats have been shown to consume substantial
      amounts of ethanol. In addition the results illustrate genetic differences with
      regard to the propensity of animals to maintain ethanol-reinforced behaviors
      under different schedules of intermittent reinforcement, and provide further
      evidence that ethanol drinking in a preference paradigm is not highly predictive
      of whether or to what extent ethanol may come to serve as a positive reinforcer.
      The results suggest that the phenomenon of ethanol drinking is a composite of at
      least three genetically independent factors governing different aspects of
      ethanol-seeking behavior: (1) a permissive factor allowing animals to readily
      overcome the aversive sensory effects of ethanol; (2) a reinforcement factor that
      determines whether a substance can come to serve as a positive reinforcer; and
      (3) a motivational factor related to the subjects' drive state with regard to
      drug seeking.

PMID- 11224305
TI  - Common genetic determinants of severity of acute withdrawal from ethanol,
      pentobarbital and diazepam in inbred mice.
AB  - Severity of drug withdrawal is in part genetically mediated, and can be indexed
      by exacerbation of the handling-induced convulsion in mice. Acute withdrawal has
      been reported following single injections of hypnotic doses of ethanol and pento
      barbital, and can be precipitated by injection of flumazenil following a single
      dose of diazepam. Results with Swiss-Webster mice indicate that the magnitude of
      ethanol and diazepam withdrawal severity did not differ across a range of doses
      in the acute paradigm. We characterized 15 inbred mouse strains for handling
      induced convulsion severity following administration of standard doses of each of
      these drugs. Significant strain differences in withdrawal severity were found for
      each drug. Two of the strains showed a tendency toward more pronounced withdrawal
      from all drugs, while six strains showed low withdrawal from all drugs. The
      correlations among strain mean withdrawal responses were analyzed to estimate
      common genetic influences. Ethanol and pentobarbital withdrawal severities were
      positively genetically correlated, indicating influence of some genes on both
      responses. A positive genetic correlation was also found between the severity of
      the withdrawal from pentobarbital and diazepam; however, diazepam and ethanol
      withdrawal severities were not found to be genetically related. These experiments
      suggest that some genes influence severity of withdrawal from more than one
      subclass of depressant drugs.

PMID- 11224306
TI  - Variations in the behavioral responses to apomorphine in different strains of
      rats.
AB  - The present experiments compared patterns of locomotor activity during repeated
      acclimation sessions and determinations of locomotion and stereotypy elicited by
      administration of the direct dopamine receptor agonist apomorphine in five inbred
      strains of rats: the results suggest that each strain can be differentiated
      phenotypically according to these behavioral responses. Brown Norway rats
      demonstrated the greatest locomotion during acclimation sessions. Low doses of
      apomorphine (0.1 and 0.32mg/kg) produced a flat body posture in Lewis animals. A
      higher dose of apomorphine (1.0mg/kg) markedly increased locomotion in Fisher
      rats. Buffalo animals showed licking during control sessions and the greatest
      increase in gnawing at higher doses of apomorphine. DA rats were less responsive
      than the other strains of apomorphine. Between-strains autoradiographic
      determination of dopamine receptor densities revealed several differences in D1
      receptors labeled by (3)H-SCH 23390 and D2/D3 receptors labeled by (125)I-NCQ 298
      in the caudate-putamen and nucleus accumbens. However, the heterogeneity of
      dopamine receptor densities was not sufficient to explain the strain-specific
      behavioral responses. These experiments demonstrate variations in behavioral and
      neurochemical characteristics of inbred strains of rats which could be used to
      model genetically determined differences in dopamine-mediated behavioral
      responses.

PMID- 11224307
TI  - Rate-dependency hypothesis and the rate-decreasing effects of d-amphetamine on
      schedule-induced drinking.
AB  - The high levels of drinking induced by intermittent food-reinforcement schedules
      are dose-dependently reduced by acute doses of d-amphetamine. The present study
      evaluated whether the effects of d-amphetamine on this schedule-induced drinking
      reflect the reduction of high rates of responding. Twenty-four rats were divided
      into six groups (n = 4) according to the interval and time durations of a
      multiple fixed-time (FT) fixed-interval (FI) schedule (15s, 30s, 60s, 120s, 240s
      and 480s). FT components were signalled by a tone and by lever withdrawal. Doses
      of 0.25 to 4.0mg/kg of d-amphetamine were administered i.p. 10min before test
      sessions. d-amphetamine produced similar dose-dependent reductions in rate of
      licking induced by FT and FI schedules. Rate-decreasing effects on operant lever
      pressing were also found after administrations of d-amphetamine. The dose
      dependent decrements produced by d-amphetamine were a function of the inter-food
      interval length in both schedule-induced and operant behaviours. These rate
      decreasing effects were rate-dependent, but d-amphetamine interacted
      differentially with control rates of adjunctive and operant behaviours, causing a
      greater suppression of the lower rates of adjunctive licking and the higher rates
      of operant lever pressing.

PMID- 11224308
TI  - Analysis of the marble burying response: marbles serve to measure digging rather
      than evoke burying.
AB  - Marble burying has been suggested as a model of obsessive-compulsive disorder
      (OCD) based on the fact that specific serotonin reuptake inhibitors selectively
      influenced this response. Studying the behaviour we observed that mice also
      exhibited intense digging activity in the absence of glass marbles. This digging
      activity showed no habituation either between sessions or within a session, and
      it could be inhibited by psychotropic drugs in a manner similar to the marble
      burying response. On the basis of the results a methodological and a theoretical
      conclusion can be drawn. First, it is concluded that glass marbles themselves do
      not necessarily provide a fear-provoking stimulus but they serve rather as a
      convenient means of measuring the intensity of digging activity. Alternative ways
      of measuring the intensity of digging gave high correlations with marble burying.
      Second, the behaviour observed is not burying (the marbles) but digging/burrowing
      (the bedding material), which is elicited by the presence of a "diggable" ground.
      The putative compulsive nature of this behaviour may add support to the
      hypothesis that marble burying may be a model of OCD.

PMID- 11224309
TI  - Resumption of ethanol-seeking behaviour in rats.
AB  - Reexposure to alcohol may induce subjective craving and relapse to drug self
      administration in ex-alcoholics. In this study, we proposed a rat model of "first
      drink"-induced drug-seeking relapse. Responding was established in Long Evans
      rats under a fixed-ratio [FR5:S(1)] schedule for oral ethanol. Substitution of
      water for ethanol solution resulted in extinction of the self-administration.
      When responding for 8% ethanol and ethanol intake were stable for at least three
      consecutive 30min sessions, ethanol delivery was discontinued and only three
      water dipper cup presentations were available upon responding (3[FR5:water]).
      When the number of active lever presses decreased to a low stable level,
      responding was considered extinguished. In Experiment 1, subjects under
      "extinction" were challenged with three 8% ethanol dipper cup presentations. The
      re-exposure to ethanol was able to significantly reinstate responding in all
      subjects. Latency to complete the ethanol presentation significantly decreased
      compared to the value observed during the previous "extinction" session. In
      Experiment 2, other subjects were tested for extinction and then reexposed to 4,
      8 or 16% ethanol. All three concentrations significantly increased active lever
      presses, but with different patterns of responding. The resumption of responding
      was linearly correlated to the ethanol concentration but no significant dose
      effect relationship was found. In Experiment 3, reexposure to 8% ethanol in
      nondeprived rats induced a resumption of responding not significantly different
      from the effect observed in a restricted diet condition. These results
      demonstrate that ethanol reexposure is able to reinstate ethanol-seeking
      behaviour in rats with a past history of ethanol self-administration, and that
      this effect does not depend on a food motivation drive related to the calorific
      value of ethanol.

PMID- 11224310
TI  - A comparison of different sensory stimuli in producing conditioned apomorphine
      effects.
AB  - In previous studies, it was shown that apomorphine-induced stereotyped behaviour
      could be conditioned when apomorphine was repeatedly paired with sensory stimuli
      (CS). Since in these experiments, the sum of various sensory stimuli were
      applied, it seemed of interest to use each sensory stimulus separately in order
      to evaluate the relevance of each of the stimuli for the development of the
      conditioned responses (CRs). Therefore, apomorphine (0.5mg/kg s.c.) was
      repeatedly (six times) paired either with an auditory, an olfactory, a tactile or
      a compound (auditory + olfactory + tactile) stimulus. On the seventh (drug-free
      test) day, the rats were injected with solvent in the presence of the CS
      previously applied. It was shown that the olfactory stimulus alone when used as
      CS produced similar CRs (in particular, stereotyped sniffing and licking) as the
      compound stimulus, whereas the other stimuli applied did not noticeably
      contribute to the development of the CRs. Furthermore, similarly to the compound
      stimulus, the olfactory stimulus, but not the auditory or tactile one, enhanced
      the apomorphine-induced stereotypies in the presence of the CS. This result
      suggests that the application of olfactory stimuli might be of particular
      relevance for the development of conditioned dopaminergic responses.

PMID- 11224311
TI  - The sigma ligand BMY-14802 as a potential antipsychotic: evidence from the latent
      inhibition model in rats.
AB  - Latent inhibition (LI) is a measure of retarded conditioning to a previously
      presented nonreinforced stimulus, that is impaired in schizophrenic patients and
      in rats treated with amphetamine. Neuroleptic drugs are known to produce two
      effects in this test paradigm: to antagonise amphetamine-induced disruption of
      LI, and to enhance LI when administered on their own. The present experiments
      tested the effects on LI of a potential antipsychotic, sigma ligand BMY-14802.
      The experiments used a conditioned emotional response (CER) procedure in rats
      licking for water, consisting of three stages: preexposure, in which the to-be
      conditioned stimulus (a tone) was repeatedly presented without being followed by
      reinforcement; conditioning, in which the preexposed stimulus was paired with
      reinforcement (a foot shock); and test, in which LI was indexed by animals'
      degree of suppression of licking during tone presentation. In Experiment 1, 20
      tone preexposures and two conditioning trials were given and the effects of 5,
      15, and 30mg/kg BMY-14802 were assessed. Experiment 2 tested the effects of 15
      and 30mg/kg on LI using ten preexposures and two conditioning trials. Experiment
      3 investigated the effects of 15 and 30mg/kg on LI using 40 preexposures and
      extended conditioning consisting of five tone-shock pairings. Experiments 4 and 5
      investigated antagonism of amphetamine-induced disruption of LI by 15 and 30mg/kg
      BMY-14802, respectively. BMY-14802 was found to antagonise amphetamine-induced
      disruption of LI and enhance LI when low numbers of preexposures and two
      conditioning trials were given, but not following extended conditioning. These
      results provide partial support for the suggestion that BMY-14802 may possess
      antipsychotic properties.

PMID- 11224312
TI  - Distinct effects of d-amphetamine and phencyclidine on the social behaviour of
      rats.
AB  - d-Amphetamine and phencyclidine (PCP) can induce a model psychosis in humans that
      resembles schizophrenia. Both drugs reproduce the positive symptoms of
      schizophrenia, but apparently only PCP mimics the negative symptoms. The purpose
      of this study was to determine the pharmacological profiles of d-amphetamine and
      PCP in the social interaction test, and to determine if they have disruptive
      effects on social behaviour in rats that may be comparable to the social
      isolation characteristic of negative symptoms. Acute and subchronic (daily for 5
      days) administration of d-amphetamine (0.7-22umol/kg) produced stereotyped
      behaviour at dosages of 10.4umol/kg and upwards without any consistent effects on
      social behaviour. In contrast, acute and subchronic PCP (0.9-29umol/kg) produced
      dose-dependent increases in stereotyped behaviour and ataxia as well as dose
      dependent reductions in the social behaviour at dosages of 3.6umol/kg and
      upwards. Thus, d-amphetamine and PCP had distinct effects on the social behaviour
      of rats. Both drugs produced stereotyped behaviour and locomotor hyperactivity,
      but only PCP dose-dependently disrupted social behaviour. This raises the
      possibility that PCP-induced social isolation in rats corresponds to the social
      isolation reported in humans under the influence of PCP, and that it can be used
      as an animal model of negative symptoms.

PMID- 11224313
TI  - Imipramine and fluoxetine prevent the stress-induced escape deficits in rats
      through a distinct mechanism of action.
AB  - A large body of evidence indicates that brain monoamines are involved in the
      pathogenesis of mental depression, as well as in the mechanism of action of most
      antidepressant treatments. The present report shows that long-term exposure to
      imipramine (IMI) or fluoxetine (FLX) was equally potent in preventing the escape
      deficits produced in rats by repeated unavoidable shocks. The acute
      administration of SCH 23390, a selective D1 dopamine receptor blocker, shortly
      before the inescapable shock session, entirely prevented IMI effect on escape
      performance, but only partially prevented that of FLX. Moreover, pindolol (an
      antagonist of beta-adrenoceptors and of serotonin 5-HT(1A) and 5-HT(1B)
      receptors) completely antagonized the efficacy of FLX in preventing escape
      deficits, whereas it did not effect the activity of IMI. The acute administration
      of propranolol failed to alter the effect of either antidepressant. It was
      concluded that in rats, the efficacy of IMI in counteracting the stress-induced
      behavioral sequelae is mainly mediated by the activation of D1 dopamine
      receptors, whereas that of FLX is largely dependent upon the stimulation of post
      synaptic 5-HT(1A) receptors. Finally, the effects of the two drugs appear to be
      totally unrelated to activation of beta-adrenoceptors.

PMID- 11224314
TI  - Suppression of corticotropin-releasing factor in the amygdala attenuates aversive
      consequences of morphine withdrawal.
AB  - The central nucleus of the amygdala is a CRF-containing limbic brain site which
      mediates both fear-like and avoidance behaviors, and intra-amygdala
      administration of a CRF antagonist blocks the increase in anxiogenic-like
      behavior characteristic of ethanol withdrawal. In order to evaluate the role of
      brain CRF in negative motivational states associated with other classes of abused
      drugs, the present studies examined the effects of suppression of amygdala CRF
      systems on the characteristic aversive state of precipitated withdrawal in
      morphine-dependent subjects. In a place conditioning paradigm, administration of
      a CRF antagonist, alpha-belical CRF (9-41) [250ng], bilaterally into the central
      nucleus of amygdala, reversed the withdrawal-induced conditioned place aversion
      produced by injection of the opiate antagonist, methylnaloxonium [500ng], into
      the same site. In a conditioned operant suppression paradigm, impairment of CRF
      neurons by immuno-targeted toxins administered into the central nucleus of
      amygdala, one month prior to testing, attenuated the decrease in response rate
      produced by exposure to distinctive sensory cues associated previously with
      systemic administration of naloxone [25ug/kg s.c.] in morphine-dependent
      subjects. These results indicate that suppression of intra-amygdala CRF systems
      weakens the aversive stimulus properties of conditioned opiate withdrawal, and
      suggest a general role for CRF in coordinating behavioral responses to negative
      motivational effects of drug withdrawal.

PMID- 11224315
TI  - A double-blind cross-over placebo-controlled trial of the effects of
      bromocriptine on psychomotor function, cognition, and mood in de novo patients
      with Parkinson's disease.
AB  - The effects of bromocriptine on potentially dissociable functions were
      investigated in this double-blind placebo-controlled trial in previously
      untreated Parkinsonian patients. Bromocriptine-induced reductions in response
      time were independent of variations in the complexity of the cognitive or motor
      programming components of reaction time tasks. These results suggest that
      bromocriptime speeds up response initiation, and it may also improve some "early"
      visual processes. No clear-cut verbal memory, visuospatial or general
      intellectual changes were produced by bromocriptine; however, further evaluation
      of the effects of bromocriptine on "executive" cognitive functions is clearly
      required. Psychiatric distress was significantly reduced when the active drug was
      administered. While mood improvements could not be statistically dissociated from
      motor improvements, review of the literature suggested that decreased emotional
      distress may have arisen through bromocriptine's action on neural circuits
      modulating mood. Some clinical implications of bromocriptine's effect on mood are
      mentioned.

PMID- 11224316
TI  - Involvement of the mesolimbic dopamine system in mediating the aversive effects
      of opioid antagonists in the rat.
AB  - An unbiased place preference conditioning procedure was used to examine the
      neural substrates mediating the aversive effects of opioid antagonists in the
      rat. Microinjection of the non-selective opioid receptor antagonist naloxone into
      either the ventral tegmental area (VTA) or the nucleus accumbens (NAc) produced
      significant aversions for an environment previously paired with its
      administration. The minimum doses producing these effects were 10.0 and 7.5ug,
      respectively. Microinjections into either the caudate/putamen or medial
      prefrontal cortex were without effect. Place aversions of equivalent magnitude
      were also observed in response to the intra-VTA or intra-NAc administration of
      the highly selective mu opioid receptor antagonist CTOP. Doses as low as 0.3ug
      resulted in significant effects. 6-hydroxydopamine lesions of the NAc attenuated
      the aversive effect of intra-VTA CTOP. Such lesions did not modify the aversive
      effects of intra-NAc CTOP; they also failed to modify the aversive effects of
      systemically administered naloxone. These data demonstrate that the blockade of
      either VTA or NAc mu opioid receptors is sufficient for the expression of the
      aversive effects of opioid antagonists. Furthermore, they suggest that whereas
      the aversive effects of intracranially applied opioid antagonists may involve
      both a mesolimbic DA-dependent (VTA) and independent (NAc) component, the
      aversive effects produced by systemically administered opioid receptor
      antagonists are independent of mesolimbic DA neurons.

PMID- 11224317
TI  - Effects of the dopamine D3-and autoreceptor preferring antagonist (-)-DS121 on
      locomotor activity, conditioned place preference and intracranial self
      stimulation in the rat.
AB  - The phenylpiperidine (-)-DS121 (S-(-)-3-(-3-cyanophenyl)-N-n-propyl piperidine)
      represents a new class of weak stimulants acting as preferential dopamine
      autoreceptor antagonists. (-)-DS121 dose-dependently increases locomotor activity
      over a wide dose range in rats after systemic administration. (-)-DS121 also
      exhibits a weak preference for the D3 receptor in in vitro binding studies. The
      relevance of this D3 preference is not clear and it is not known whether the D3
      receptor site influences reward mechanisms. The present results showed that (-)
      DS121 induced place conditioning in the dose range 3.3-13.3mg/kg s.c. as did d
      amphetamine (0.25-4.0mg/kg, s.c.). However, in contrast to d-amphetamine, (-)
      DS121 failed to facilitate infracranial self-stimulation in the dose range that
      produced place conditioning. Local bilateral infusion of (-)-DS121 (0.05
      53.0ug/side) into the nucleus accumbens or ventral tegmental area did not produce
      locomotor stimulation. A weak but significant increase in locomotor activity was
      detected after bilateral infusion of (-)-DS121 (66.3ug/side) into the lateral
      ventricles. This study suggests that the behavioural stimulant (-)-DS121 does not
      possess strong reward-facilitating properties and that local application in
      either the terminal or somatodendritic regions of the mesolimbic pathway does not
      produce the same degree of locomotor activity as seen after systemic
      administration.

PMID- 11224318
TI  - Behavioural effects of novel benzodiazepine (omega) receptor agonists and partial
      agonists: increases in punished responding and antagonism of the
      pentylenetetrazole cue.
AB  - In recent years a number of novel compounds have been described with affinity and
      specificity for BZ (omega) receptors. While some of these agents appear to act,
      like benzodiazepines themselves, as full agonists at different receptor subtypes
      (e.g. suriclone), several non-selective partial agonists (e.g. bretazenil) have
      been described, as have a number of BZ(1) (omega(1)) selective drugs (e.g.
      zolpidem). Previous work has reported a number of differences between the
      behavioural effects of some of these drugs and those of benzodiazepines; however,
      very few studies have attempted systematic comparisons of a large number of drugs
      in different procedures. In the present study a wide range of BZ (omega) receptor
      ligands was studied using two behavioural methods in rats: unpunished and
      punished food-reinforced operant responding and the discriminative stimulus
      effects of pentylenetetrazole. Punished operant responding showed increases with
      the benzodiazepines, chlordiazepoxide and clorazepate, the non-benzodiazepines,
      saripidem, CL 273,547 and F 2692 (limited effect at a single dose) and the
      partial agonists bretazenil and Ro 19-8022, but the BZ(1) selective agents,
      alpidem, abecarnil and CL 284,846, did not increase rates of punished operant
      responding. Rates of unpunished responding were decreased by higher doses of all
      drugs except bretazenil and Ro 19-8022. Dose-related antagonism of the
      pentylenetetrazole (18mg/kg) discriminative stimulus was produced by several
      benzodiazepines, by the partial agonists bretazenil, Ro 19-8022 and divaplon, and
      by suriclone, saripidem and CL 273,547. The BZ(1) (omega(1)) selective drugs
      abecarnil, CL 284,846, zolpidem, CL 218,872 and alpidem were also active in
      blocking pentylenetetrazole but produced only partial antagonism which was not
      clearly dose-related. The results show that novel BZ (omega) receptor ligands do
      not always produce a behavioural profile identical to that shown by
      benzodiazepines. In particular, BZ(1) (omega(1)) selective drugs do not give rise
      to clear increases in punished operant responding and have only limited efficacy
      in blocking the pentylenetetrazole cue. These effects may be due to the marked
      propensity of BZ(1) (omega(1)) selective drugs to decrease operant response
      rates.

PMID- 11224319
TI  - Effects of reinforcer sweetness and the D2/D3 antagonist raclopride on
      progressive ratio operant performance.
AB  - Previous studies have reported that DA receptor antagonists suppress most
      behaviours; however, a paradoxical increase in performance may be seen in tests
      of operant or consummatory behaviours maintained by very sweet rewards, which lie
      on the descending limb of the inverted U-shaped concentration-performance
      function (i.e., under conditions where performance decreases as sweetness
      increases). Despite the low performance levels associated with very sweet
      reinforcers, preference studies indicate that they are nonetheless more
      rewarding. In the present study, the hypothesis that reinforcer efficacy is
      monotonically related to reinforcer sweetness was tested using a geometric
      progressive ratio reinforcement schedule, in which increasing numbers of
      responses were required to earn successive reinforcers (1, 2, 4, 8,.); the amount
      of work the animal emits in order to obtain an increasingly infrequent reinforcer
      is assumed to provide a measure of the magnitude of its rewarding effect. Three
      groups of rats were trained on this schedule, using as reinforcers food pellets
      containing 1%, 10% and 95% sucrose, respectively. Under conditions of continuous
      sucrose-pellet reinforcement, the highest response rates were maintained by the
      10% sucrose pellets. However, under the progressive ratio schedule, performance
      was monotonically related to sucrose concentration. The dopamine D2/D3 receptor
      antagonist raclopride dose-dependently suppressed progressive ratio performance
      in all three groups.

PMID- 11224320
TI  - Environment modifies the expression of behavioral sensitization produced by
      methamphetamine: behavioral and neurochemical studies.
AB  - Effects of environmental modulation of methamphetamine (MA)-induced behavior on
      the establishment and mode of expression of behavioral sensitization were
      examined. Rats received daily injection of MA for 10 days (1mg/kg, s.c.). Half of
      them were immediately returned to the home cage (home cage group) and the other
      half were individually confined in a cylinder with a diameter of 13cm placed
      inside the home cage for 3h after each injection (small cage group). Gross
      observations revealed that rats which received MA in the small cage did not
      locomote but showed sniffing and rearing. The third group received saline in the
      home cage (saline control group). After a 7-8 day or 17-18 day withdrawal period,
      all groups were injected with MA (1mg/kg or 0.5mg/kg) in their home cages. The
      home cage group showed significant enhancement in horizontal motor activity
      compared to the saline control group, indicating the establishment of locomotor
      sensitization. In contrast, the small cage group showed no or slight enhancement
      in the motor activity. However, they showed significantly more stereotyped
      behavior compared to both the saline control and the home cage groups.
      Microdialysis studies revealed no enhancement in the ability of MA to increase
      dopamine release from the nucleus accumbens in either the home or the small cage
      group compared to the saline control group, when examined after either a 7-8 day
      or a 17-18 day withdrawal period. These results suggest that environmental
      modulation of actual movement under the stimulant effect modifies the pattern and
      character of the stimulant-induced behavior in sensitized animals. The
      neurochemical basis of the establishment of behavioral sensitization and the
      environmental modification of its expression remain unknown.

PMID- 11224321
TI  - Effects of D1 dopamine agonists on schedule-controlled behavior in the squirrel
      monkey.
AB  - Behavioral effects of several dopamine D1 receptor agonists were compared with
      those of cocaine and (+)-amphetamine in squirrel monkeys trained to press a
      response key under a fixed-interval schedule of electric shock presentation.
      Cocaine (0.03 to 0.3mg/kg) and (+)-amphetamine (0.01 to 0.1mg/kg) at low to
      intermediate doses increased rates of responding under the fixed-interval
      schedule; at higher doses each of these drugs decreased response rates. In
      contrast, neither full nor partial D1 receptor agonists produced reliable
      increases in response rates. Rather, these drugs decreased rates of responding in
      a dose-related manner. These results with schedule-controlled behavior in
      primates support earlier findings in rodents that indicate that D1 agonist
      actions result in effects quite different from the characteristic psychomotor
      stimulant effects produced by cocaine or (+)-amphetamine; and they further
      suggest that those characteristic stimulant effects are more probably due to
      stimulation of other dopamine receptors.

PMID- 11224322
TI  - Discriminated conditioned taste aversion for studying multi-element stimulus
      control.
AB  - The effects of morphine pre-treatment interval on the stimulus control exerted by
      a multi-element stimulus consisting of morphine (5.6mg/kg), saccharin (0.2%,
      w/v), and a ball-bearing drinking nozzle in a discriminated taste aversion
      procedure were examined. In this discriminated aversion procedure, rats received
      injections of LiCI following presentation of this multielement stimulus, and
      injections of saline following the saline, water, and non-ball-bearing nozzle
      composite stimulus. These paired rats were compared to unpaired rats that
      received saline injections rather than LiCI injections following presentation of
      the multi-element stimulus. Morphine pre-treatment times of 5, 10, and 20min were
      examined in groups of 12 paired and 6 unpaired rats. The discrimination was
      rapidly learned under all three pre-treatment intervals. In subsequent testing
      with each individual stimulus element and combinations of two stimulus elements,
      stimulus control was clearly exerted by both morphine and saccharin. Paired rats
      drank less saccharin than unpaired rats, and less saccharin than water.
      Similarly, paired rats drank less fluid following morphine administration than
      following saline administration, and less fluid than unpaired rats following
      morphine administration. Control by the nozzle type was also apparent in
      significant interactions between the nozzle and morphine or saccharin and pairing
      with LiCI. In general, pre-treatment time did not influence the stimulus control
      that developed. However, at the two shorter pre-treatment times there was some
      indication that a conditioned taste aversion to morphine was developing in the
      unpaired rats. These experiments indicate that such discriminated taste aversion
      procedures may be viable methods for studying the contextual control of how drugs
      function as discriminative stimuli, and that longer drug pre-treatment times may
      be desirable in such procedures.

PMID- 11224323
TI  - Effects of competitive and noncompetitive GABA(A) antagonists on the acquisition
      of a discrimination in squirrel monkeys.
AB  - There is evidence that low doses of convulsant agents may enhance acquisition
      under various behavioral procedures. The following experiments were undertaken to
      establish whether the putative GABA(A) antagonist pentylenetetrazole, and known
      GABA(A) receptor antagonists picrotoxin, picrotoxinin and bicuculine, might also
      enhance acquisition. Learning was studied under two different schedules of food
      presentation using the technique of repeated acquisition. Under this procedure,
      subject were required to acquire a different three-response sequence each
      session. Sequence completions were reinforced under a fixed-ratio five (FR 5)
      schedule, which engendered a low level of errors. A chain strained-ratio schedule
      was also studied because it engendered a high level of errors. Pentylenetetrazole
      (PTZ) (0.32-32mg/kg) generally produced a dose-related decrease in responding at
      higher doses (10-32mg/kg), while at lower doses (0.32-5.6mg/kg) response rate was
      not affected. PTZ generally disrupted accuracy of responding only at doses that
      decreased the rate of responding. Like PTZ, the noncompetitive GABA(A) receptor
      antagonist picrotoxin decreased the overall rate of responding and disrupted
      accuracy only at the higher doses tested (0.13-0.32mg/kg) in three of four
      subjects. At low doses (0.0032-0.1mg/kg), response rates and accuracy were
      unaffected when compared to the control ranges. Picrotoxinin, an active
      metabolite of picrotoxin, increased errors at doses that decreased the overall
      rate of responding. Conversely, the competitive GABA(A) receptor antagonist
      bicuculline (0.0032-0.56mg/kg) had no effect on accuracy and only decreased the
      rate of responding at doses that produced convulsions. Under the chain strained
      ratio schedule, PTZ and picrotoxinin failed to enhance acquisition. These data
      suggest that pentylenetetrazole, picrotoxin, picrotoxinin and bicuculline do not
      reliably enhance acquisition in the squirrel monkey, and that differences exist
      between competitive and noncompetitive GABA(A) antagonists with regard to their
      effects on acquisition processes in the squirrel monkey. d-amphetamine, on the
      other hand, disrupted acquisition under the fixed-ratio schedule while at certain
      doses it enhanced acquisition under the strained-ratio schedule. The data also
      suggest that classical brain stem and cortical stimulants differ in terms of
      their ability to enhance acquisition under a strained-ratio schedule and that
      these differences may relate to their effects on conditioned reinforcement.

PMID- 11224324
TI  - Learning impairment following acute administration of the calcium channel
      antagonist nimodipine in mice.
AB  - The effects of acute systemic administration of the Ca(2+) channel antagonist
      nimodipine were examined on learning capacities of adult Swiss mice. Tests
      included spontaneous alternation behaviour, for spatial working memory; and step
      down passive avoidance and place learning in a water maze, for long-term memory.
      Nimodipine markedly impaired spontaneous alternation at doses of 0.3-1mg/kg i.p.,
      and passive avoidance at doses of 0.3-3mg/kg i.p., as compared to the vehicle
      treated animals. At 0.3mg/kg i.p., the drug did not alter motility in an open
      field, but significantly decreased performances in training trials and retention
      in the water maze. Subchronic nimodipine 0.3 and 1mg/kg once a day i.p. for 10
      days) did not affect performances in the Y-maze and passive avoidance tests.
      These results show that acute nimodipine administration alters learning in adult
      mice, and argue for an involvement of voltage-dependent Ca(2+) channels in
      learning.

PMID- 11224325
TI  - Behavioral and subjective effects of DN-2327 (pazinaclone) and alprazolam in
      normal volunteers.
AB  - DN-2327 (pazinaclone) is a new non-benzodiazepine compound which has high
      affinity for benzodiazepine receptors. The acute behavioral effects and abuse
      liability of DN-2327 (2, 4 and 8mg) were compared to those of the benzodiazepine
      anxiolytic alprazolam (0.25, 0.5 and 1mg) in ten normal adult male volunteers
      using a double-blind, placebo-controlled, outpatient design. For both drugs, the
      neck effect occurred approximately 1.5h after drug administration. Both drugs
      also produced comparable dose-related effects on several measures related to
      sedation, as well as on subject- and observer-rated strength of drug effect. Both
      alprazolam and DN-2327 produced dose-related impairments on various performance
      measures; on some tasks, the impairment was greater for DN-2327. In contrast,
      there were no differences between DN-2327 and alprazolam on observer-rated
      measures. Although no measures of drug-taking were made in this study, to the
      extent that self-reported effects predict reinforcing effects, the data suggest
      little liability for abuse of the two compounds in this subject population.
      Ratings of 'drug liking' and 'willing to take the drug again' were not increased
      following alprazolam. Although DN-2327 did not increase ratings of 'willing to
      take the drug again', DN-2327 did produce small but significant increases on
      ratings of 'drug liking'. Overall, these results suggest that the non
      benzodiazepine DN-2327 has a pharmacological profile that is similar to that of
      benzodiazepines.

PMID- 11224326
TI  - Placebo-effects contribute to differences in the acquisition of drug
      discrimination by humans: a retrospective analysis.
AB  - Adult human volunteers (n = 50) were trained to discriminate triazolam (TRZ,
      0.32mg/70kg, p.o.) from placebo. Based on a criterion that required greater than
      80% capsule-appropriate responding during each of four test sessions, 19 subjects
      were designated non-discriminators (NDs) and 31 were designated discriminators
      (Ds). NDs and Ds did not differ significantly in age, weight, gender or previous
      drug use and generally reported similar effects following TRZ. NDs reported
      greater effects following placebo than Ds on several measures, including 'good',
      'bad', 'high' and sedative drug effects, suggesting that NDs in this study were
      'placebo reactors'. These results show that NDs and Ds of TRZ differed in self
      reported responses and suggest a close relationship between acquisition of a drug
      discrimination and self-reported effects of drugs. Moreover, greater placebo
      effects may hinder acquisition of TRZ discrimination.

PMID- 11224327
TI  - The effects of selective and non-selective monoamine oxidase (MAO) inhibitors on
      conflict behavior in the rat.
AB  - Conflict behavior in rats was examined over the course of several weeks of
      chronic treatment with selective and non-selective monoamine oxidase inhibitors
      (MAOIs). In daily 10min sessions, rats were trained to drink from a tube which
      was occasionally electrified (0.5mA). Electrification was signalled by the
      presence of a tone. Within 3-4 weeks, control (i.e. non-drug) conflict behavior
      had stabilized (30-40 shocks and 8-12ml water/session) and drug testing began.
      Chronic administration (two injections/day for 8 weeks) with a non-selective
      (i.e. MAO-A and MAO-B inhibiting) dose of pargyline (15mg/kg) resulted in a time
      dependent increase in punished responding. In contrast, chronic administration of
      the MAO-A selective inhibitor (clorgyline; 1.0mg/kg, 2mg/kg), the MAO-B selective
      inhibitor deprenyl (5mg/kg) or MAO-B inhibiting doses of pargyline (1.0mg/kg,
      5mg/kg) were without effect. Finally, chronic treatment with the combination of a
      low dose of clorgyline (1.0mg/kg) and a low dose of pargyline (1.0mg/kg) did
      result in a time-dependent increase in punished responding. These results suggest
      that inhibition of both MAO-A and MAO-B is required for the eventuation of the
      anxiolytic effect resulting from chronic MAOI treatment.

PMID- 11224328
TI  - Subchronic intermittent nicotine treatment enhances ethanol-induced locomotor
      stimulation and dopamine turnover in mice.
AB  - Most drugs of abuse enhance mesolimbic dopaminergic transmission and locomotor
      activity in laboratory animals and, when given repeatedly, further increase these
      measures, a phenomenon termed sensitization. Sensitization-related
      neuroadaptations have been proposed to be important in the development and
      maintenance of addiction. It has been suggested that both ethanol and nicotine
      interfere with central nicotinic acetylcholine receptors located on brain
      dopamine neurons, a mechanism of action that may provide a basis for the often
      observed co-administration of these drugs of abuse. In this study we investigated
      the effects of a challenge with ethanol (2.5g/kg, i.p.) or nicotine (0.2mg/kg,
      s.c.) on locomotor activity and monoamine turnover in mice subchronically
      pretreated with nicotine. Nicotine pretreatment significantly enhanced the
      ethanol-induced locomotor stimulation and elevation of dihydroxyphenylacetic acid
      (DOPAC)/dopamine (DA) quotient in the brain. These results suggest that neuronal
      mechanisms related to the locomotor stimulatory effects of ethanol may be
      sensitized by preexposure to nicotine.

PMID- 11224329
TI  - Behavioral effects of neuropeptide Y receptor agonists in the elevated plus-maze
      and fear-potentiated startle procedures.
AB  - Evidence from animal studies has led to the proposal that neuropeptide Y (NPY)
      has anxiolytic-like effects in rats after intracerebroventricular (i.c.v.)
      administration. The purpose of the present study was to extend these observations
      by examining the behavioral effects of a series of NPY receptor agonists
      including NPY, peptide YY (PYY), the NPY fragment 2-36 (NPY(2-36)), the Y(1)
      agonist [Leu(31), Pro(34)]-NPY and the Y(2) agonist NPY fragment 13-36 (NPY(13
      36)), in two established anxiety models in rats: the elevated plus-maze and the
      fear-potentiated startle procedures. In the elevated plus-maze procedure, i.c.v.
      PYY (0.07-2.3nmol), NPY (0.07-2.3nmol), NPY(2-36) (0.07-2.3nmol). [Leu(31),
      Pro(34)]-NPY (0.7-7nmol), but not NPY(13-36) (0.7-7nmol), increased preference
      for the open arms of the plus-maze in a dose-dependent manner. In an acoustic
      startle paradigm, NPY, PYY and NPY(2-36) inhibited fear-potentiated startle over
      the dose-range of 0.23-2.3nmol. [Leu(31), Pro(34)]-NPY (2.3-13.2nmol) also
      attenuated fear-potentiated startle, whereas NPY(13-36) (up to 13.2nmol) had no
      effect. Taken together, these findings demonstrate that NPY, PYY and NPY(2-36)
      have anxiolytic-like effects that are likely mediated by Y(1) receptors.

PMID- 11224330
TI  - A comparison of the reinforcing efficacy of PCP, the PCP derivatives TCP and
      BTCP, and cocaine using a progressive ratio schedule in the rat.
AB  - This study was designed to compare the reinforcing efficacy of PCP
      (phencyclidine:phenylcyclohexyl-piperidine) and the PCP-derivatives BTCP (N-[1-(2
      benzo(b)thiophenyl) cyclohexyl]piperidine) and TCP (N-[1-(2-thienyl)cyclohexyl]
      piperidine) to that of cocaine, using a progressive ratio schedule of
      reinforcement (PR). On the PR schedule the number of responses required to obtain
      an i.v. infusion of drug was escalated with each injection until a breaking point
      was reached when the animal stopped responding. Since BTCP has an affinity for
      the DA uptake site comparable to that of cocaine, it was hypothesized that BTCP
      and cocaine would show similar patterns of self-administration and comparable
      breaking points. In contrast, the high affinity of TCP and PCP for the NMDA-ion
      channel complex suggested that these two compounds would also support comparable
      self-administration behaviors. Rats were trained to self-administer i.v. cocaine
      during daily 5h sessions under a fixed-ratio-1 (FR1) schedule. Once consistent
      lever-pressing behavior was established, BTCP, PCP or TCP was substituted for
      cocaine. Under the FRI schedule, BTCP elicited a regular pattern of lever
      pressing, unlike PCP and TCP. However, under the PR schedule BTCP elicited
      breaking points comparable to those produced by equivalent doses of cocaine,
      whereas TCP and PCP produced considerably lower breaking points. These results
      suggest that BTCP has comparable rewarding properties to that of cocaine, and
      that like those of cocaine they are most probably mediated through a site of
      action at the DA transporter. In contrast, the relatively weak reinforcing
      efficacy of PCP and TCP would correlate better with their primary site of action
      on the PCP binding site within the NMDA-ion channel complex.

PMID- 11224331
TI  - Behavior genetic investigation of the relationship between spontaneous locomotor
      activity and the acquisition of morphine self-administration behavior.
AB  - There is a significant degree of individual variability in response to drugs of
      abuse. A goal of behavior genetic studies has been to determine the extent to
      which observed heterogeneity in drug use can be attributed to genetic and
      environmental factors and to identify the neurobiological factors involved in
      vulnerability. Recent hypotheses regarding the predictive value of spontaneous
      locomotor activity in the acquisition of drug-reinforced behavior are amenable to
      testing using a behavior genetics approach. Genetic differences in locomotor
      response to a novel environment were determined in naive and catheterized Lewis,
      F344, NBR and ACI rats. Operant drug-reinforced behavior was examined in a 23h
      access paradigm in which each lever press by a rat produced a 1mg/kg injection of
      morphine with a 30s timeout period (FR 1:TO 30"). Acquisition (7 days),
      extinction (6 days) and reacquisition (7 days) of morphine self-administration
      behavior was investigated in all four inbred strains. Large genetic differences
      in the rate of acquisition and extinction of morphine self-administration were
      found. Lewis rats responded at high rates beginning in the first two days,
      whereas F344 rats initially responded at low rates and responding increased
      gradually over seven days. NBR and ACI rats responded at intermediate levels.
      When vehicle was substituted for drug there was a significant effect of genotype
      on the rate of extinction; F344 and ACI increased responding to greater than 175%
      of drug-response levels, whereas the Lewis response rate decreased gradually and
      NBR response rate decreased immediately during the first several days. When drug
      was available again, rates of reacquisition did not differ from original
      acquisition rates. Drug maintained significantly greater amounts of behavior than
      vehicle in the Lewis, F344 and NBR rats and was thus shown to serve as a positive
      reinforcer in these three strains under these conditions. There was a significant
      genetic correlation among strains between drug intake during the first five days
      of acquisition and spontaneous locomotor response to a novel environment in
      catheterized rats. Only the ACI rats showed a significant within-strain
      correlation. The positive relationship between rate of acquisition of self
      administration behavior and locomotor activity suggests that these two traits are
      influenced by common or closely linked genes. To this end, the neurobiological
      substrates that mediate spontaneous locomotor behavior under these environmental
      conditions may act, in part, as a template for determining the neurobiological
      substrates that mediate the relative rate of acquisition of morphine-taking
      behavior under these conditions.

PMID- 11224332
TI  - Benzodiazepine receptor ligands have no specific action on working memory in a
      delayed conditional discrimination task in rats.
AB  - We investigated effects of benzodiazepine (BDZ) receptor ligands on working
      memory in a delayed conditional discrimination (DCD) task. The BDZ receptor full
      agonist midazolam (0.1-1.0mg/kg) dose-dependently impaired performance
      independent of delay, indicating no specific effect on working memory. The non
      sedative BDZ receptor partial agonist bretazenil (0.06-0.6mg/kg), the inverse
      agonist beta-CCM (0.05-0.45mg/kg), the partial inverse agonist FG 7142 (0.5
      5.0mg/kg), the antagonist flumazenil (1-10mg/kg), and the antagonist ZK 93 426 (1
      10mg/kg) did not significantly affect performance. It is concluded that BDZ
      ligands do not affect working memory in a positively-motivated DCD task.
      Midazolam also impaired performance in the no-delay condition, suggesting loss of
      stimulus control, possibly through an attentional impairment.

PMID- 11224333
TI  - Effects of ifenprodil on stimulatory, discriminative stimulus, and convulsant
      effects of cocaine.
AB  - Ifenprodil, like cocaine, binds to the dopamine transporter and blocks uptake of
      dopamine. In this study, the ability of ifenprodil to mimic, enhance or block
      behavioral and toxic effects of cocaine was evaluated. Fixed-interval responding
      maintained by food presentation in rats was increased by cocaine but decreased by
      ifenprodil. Low rates of responding during timeout periods were also increased by
      cocaine but not ifenprodil. Ifenprodil neither increased locomotor activity nor
      augmented the stimulatory effect of cocaine; however, ifenprodil attenuated the
      stimulant effects of cocaine at doses 0.5 log unit lower than those required to
      reduce spontaneous activity when given alone. Ifenprodil neither substituted for
      nor augmented the discriminative stimulus effects of cocaine in rats
      discriminating 10mg/kg cocaine from saline. In contrast to cocaine, ifenprodil
      did not produce convulsions or signs of proconvulsant activity, and ifenprodil
      reduced the percentage of mice convulsing in the presence of cocaine. These
      results suggest that pharmacological actions in addition to blockade of dopamine
      uptake or novel interactions with the dopamine transporter may contribute to the
      non-stimulant behavioral profile and cocaine-blocking actions of ifenprodil.

PMID- 11224334
TI  - Learned suppression of stereotypy in amphetamine-treated rats: implications for
      understanding tolerance to amphetamine 'anorexia'
AB  - The purpose of this study was to determine whether amphetamine-treated rats can
      learn to suppress stereotyped movements in order to feed. Rats implanted with
      cannulae were reinforced with intraoral infusions of milk for holding their heads
      stationary within a narrow area of space defined by intersecting photobeams. Four
      of six rats given chronic injections of amphetamine (2mg/kg) learned the
      response. The amount of milk ingested as a result of the infusions increased over
      trials at a rate that was comparable to that of rats given milk in bottles.
      Despite the development of such 'tolerance', analysis of the temporal
      distribution of photobeam interruptions revealed residual effects of the drug.
      Specifically, amphetamine-treated rats had longer latencies to initiate infusions
      and displayed a more fragmented pattern of responding than did saline controls.
      These results demonstrate that rats can learn to inhibit amphetamine-induced
      sterotypy and support the view that tolerance to amphetamine 'anorexia' involves
      learning to suppress stereotyped movements that interfere with feeding. Parallels
      to the suppression of involuntary movements in humans are noted.

PMID- 11224335
TI  - Assessment of the discriminative stimulus effects of the optical isomers of
      ecstasy (3,4-methylenedioxymethamphetamine; MDMA).
AB  - The discriminative stimulus effects of the stereoisomers of 3,4
      methylenedioxymethamphetamine (MDMA) were studied in rats trained to discriminate
      1.25mg/kg of (+)-MDMA or 3.5mg/kg of (-)-MDMA from saline, in a two lever, water
      reinforced, drug discrimination situation. The isomers of MDMA and 3,4
      methylenedioxyamphetamine (MDA) substituted completely for both training drugs.
      The stimulants amphetamine and cocaine did not substitute for either MDMA isomer.
      The hallucinogens (+/-)-2,5-dimethoxy-4-methylamphetamine (DOM), (+)-lysergic
      acid diethylamide (LSD), and mescaline failed to substitute completely for (+)
      MDMA. Similarly, DOM and mescaline did not substitute for (-)-MDMA; however, LSD
      did substitute for this isomer at a dose of 0.06mg/kg but not at higher doses.
      Substitution tests with 5-HT-releasing agents revealed that fenfluramine
      substituted partially for (+)-MDMA and completely for (-)-MDMA, while p
      chloroamphetamine substituted completely for both isomers of MDMA. When given in
      combination with (+)-or (-)-MDMA, neither the 5-HT(2) antagonist pirenpirone nor
      the less selective 5-HT antagonist metergoline consistently blocked drug
      appropriate responding. These results indicate that the stereoisomers of MDMA and
      MDA have similar discriminative stimulus properties. More importantly, the
      present findings suggest that 5-HT release may be important for the
      discriminative stimulus effects of (+)-and (-)-MDMA. Actions at 5-HT(2)
      receptors, however, do not appear to be critical.

PMID- 11224336
TI  - Effect of SR 59026A, a new 5-HT(1A) receptor agonist, on sexual activity in male
      rats.
AB  - The effect of SR 59026A, a new selective 5-HT(1A) receptor agonist, was evaluated
      on sexual behaviour of male rats in different experimental conditions. SR 59026A
      (1-10mg/kg p.o.) stimulated the copulatory behaviour of sexually experienced
      rats, as evidenced by a decrease in the number of pre-ejaculatory mounts and
      intromissions and a shortening of the ejaculation latency. SR 59026A also
      facilitated the sexual behaviour of naive male rats characterized by a low level
      of sexual performance: over the same dose range, the percentage of naive males
      that copulated was significantly increased and the ejaculation latency reduced.
      In experiments designed to evaluate the onset of sexual satiation, SR 59026A (1
      and 3mg/kg) increased significantly the number of ejaculations and delayed the
      time of sexual satiation. Finally, in agreement with studies on other 5-HT(1A)
      receptor agonists, SR 59026A did not modify the occurrence of spontaneous
      erections in isolated male rats. Therefore, the present study shows that SR
      59026A improves the sexual performance of male rats in a number of different
      experimental models, and the compound may prove to be of interest for the
      treatment of certain states of human male sexual dysfunction.

PMID- 11224337
TI  - Effects of scopolamine and its quaternary analogue in the murine elevated plus
      maze test of anxiety.
AB  - Several lines of evidence suggest that muscarinic cholinergic receptors may play
      a role in fear/anxiety reactions in animals. In the present study, the
      behavioural effects of the muscarinic receptor antagonist scopolamine (0.125
      1.0mg/kg) were examined in male mice exposed to the elevated plus-maze. In
      contrast to scopolamine methyl bromide, which was behaviourally inert under
      present test conditions, scopolamine hydrobromide produced behavioural changes
      indicative of enhanced anxiety. The effects included a reduction in percentage of
      open arm entries and a marked stimulation of risk assessment measures (i.e.
      stretched attend postures and closed arm returns), as well as more subjective
      signs of enhanced fear/anxiety such as vocalisation, struggling and escape
      oriented behaviour. Although scopolamine also enhanced total arm entries, perhaps
      suggesting a general stimulant action, this effect was specific to the closed
      arms and was not accompanied by systematic increases in either rearing or head
      dipping. Data are discussed in relation to the possible involvement of central
      muscarinic substrates in risk assessment behaviour in animals and hypervigilance
      states in humans.

PMID- 11224338
TI  - The effect of risperidone on schedule-induced polydipsia.
AB  - The effects of risperidone on the acquisition of schedule-induced polydipsia in
      rats were investigated in a chronic dose regime followed by seven days of
      withdrawal. Risperidone dose-dependently suppressed water intake and number of
      panel pushes. Drinking efficiency and free water intake in home cages were
      unchanged. By comparing the effects of risperidone in the present paper with the
      effects of different-neuroleptics in the same procedure from an earlier study, it
      appears that the effect of risperidone is intermediary to that of the 'typical'
      and 'atypical' neuroleptics. It may be concluded that risperidone acts as an
      atypical neuroleptic compound; however, increasing the dose only two-fold will
      cause EPS.

PMID- 11224339
TI  - Disruption of temporal discrimination by drugs of abuse: I. Unmasking of a color
      bias.
AB  - Pigeons were trained to discriminate the length of a delay period (3s vs. 10s).
      Under control conditions, pigeons were able to discriminate between the two delay
      period lengths with a high degree of accuracy (>90%). When delays of 1, 3, 5, 7,
      9 and 11s were randomly presented, the percentage of responses appropriate to the
      10s delay increased as a function of increasing delay length. Dose-response
      curves determined for a series of drugs of abuse showed that pentobarbital,
      diazepam and phencyclidine displayed the greatest efficacy in disrupting the
      discrimination. The decrease in accuracy was a function of both a decrease in the
      ability of the pigeon to discriminate the passage of time, and the expression of
      a drug-induced red color bias. When the stimulus colors were changed, these drugs
      still decreased accuracy of the discrimination without any evidence of a color
      bias. Morphine disrupted the discrimination at doses which produced marked
      response suppression; there was no evidence of a drug-induced color bias.
      Delta(9)-THC failed to produce any significant effect on the discrimination. d
      amphetamine and cocaine initially had no effect; however, upon subsequent
      determinations and when the stimulus colors were changed during the last part of
      the experiment, they did disrupt discrimination performance. These results show
      that drugs of abuse have differential effects on temporal discrimination, with
      some drugs affecting temporal discrimination at doses that do not suppress
      responding, some affecting the discrimination at doses that decrease response
      rates, and others that do not appear to affect temporal discrimination. Only
      sedative/hypnotic drugs disrupted temporal discrimination in part by producing a
      red-color bias.

PMID- 11224340
TI  - Comparison of changes in extracellular dopamine concentrations in the nucleus
      accumbens during intravenous self-administration of cocaine or d-amphetamine.
AB  - Changes in extracellular concentrations of dopamine (DA) were measured in vivo in
      the nucleus accumbens of the rat during intravenous self-administration of either
      cocaine (0.25, 0.5, 1.0mg/infusion) or d-amphetamine (0.05, 0.1, 0.2mg/infusion).
      Drug intake was limited to 12 self-administered infusions per session for each
      drug/dose combination. Changes in extra-cellular DA concentrations were measured
      by two different techniques: chronoamperometry in conjunction with chronically
      implanted stearate-modified carbon paste electrodes, or intracerebral
      microdialysis with off-line analyses using high performance liquid chromatography
      with electrochemical detection (HPLC-ED). Significant increases in extracellular
      DA concentrations were observed with both in vivo techniques during self
      administration of each dose of cocaine or d-amphetamine. For each drug, the
      magnitude of change during the first hour of the test session was comparable
      across doses. However, the change observed over the first 2h period, as measured
      by microdialysis and HPLC-ED, revealed a dose effect for cocaine, but no dose
      response effect for d-amphetamine. The duration of the drug-induced elevation was
      increased significantly as a function of dose with both cocaine and d
      amphetamine. Data from the microdialysis experiments indicated that the high dose
      of d-amphetamine (0.2mg/infusion) produced a significantly greater increase in
      extracellular DA concentrations in the nucleus accumbens than did the high dose
      of cocaine (1.0mg/infusion), but that comparable changes were induced by doses of
      0.1mg/infusion of d-amphetamine and 1.0mg/infusion of cocaine, respectively. Each
      dose of both psychostimulant drugs also produced a significant decrease in
      dihydroxyphenylacetic acid (DOPAC) levels. The latter finding indicated that the
      electrochemical signal measured in these studies was not due to the oxidation of
      DOPAC. These results confirm that self-administration of cocaine or d-amphetamine
      by the rat is accompanied by a significant increase in extracellular DA
      concentrations in the nucleus accumbens. The fact that two different psychomotor
      stimulant drugs of abuse have qualitatively similar neurochemical correlates when
      self-administered, adds credence to the hypothesis that their reinforcing
      properties are related to dynamic changes in DA concentrations in the ventral
      striatal region of the brain.

PMID- 11224341
TI  - Comparison of the effects of full and partial allosteric modulators of GABA(A)
      receptors on complex behavioral processes in monkeys.
AB  - Two baselines involving a repeated acquisition task were used to assess the
      effects of bretazenil, imidazenil, and triazolam. The first baseline was a
      multiple schedule of repeated acquisition and performance of conditional
      discriminations. In the first component, the subject acquired a four-response
      chain by responding sequentially on three keys in the presence of different
      combinations of colors and geometric forms displayed on a center key. Acquisition
      of the discrimination was defined by a decrease in errors as the session
      progressed. In the performance component, the four-response chain was the same
      each session. Incorrect responses in either component produced a 5s time out
      during which responding had no programmed consequence. The second procedure,
      which has been used to evaluate the effects of drugs on memory, involved the
      acquisition of a discrimination, followed by a 1h delay and a retest of the same
      discrimination to assess retention. Triazolam (0.32 and 0.56mg/kg) administered
      alone, produced dose-related decreases in response rate in each component. In
      addition, triazolam also produced a dose-related increase in percentage errors in
      acquisition with no effect in performance. Triazolam (0.32mg/kg) eliminated
      retention (0 percent savings) in the memory task. Bretazenil (0.1-5.6mg/kg) or
      imidazenil (0.1-1.8mg/kg) administered alone had little or no effect on either
      rate of responding or accuracy in either component. Furthermore, bretazenil but
      not imidazenil disrupted retention at the higher doses tested. The combination of
      imidazenil or bretazenil with triazolam produced dose-related attenuation of the
      disruptive effects of triazolam on both behavioral baselines. These data suggest
      that the disruptive effects of benzodiazepines on learning and memory may be a
      function of the intrinsic efficacy of these compounds at different GABA(A)
      receptor subtypes.

PMID- 11224342
TI  - Pretreatment with the dopamine agonist 7-OH-DPAT shifts the cocaine self
      administration dose-effect function to the left under different schedules in the
      rat.
AB  - This study tested the hypothesis that administration of the dopamine agonist 7
      hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) shifts the cocaine self
      administration dose-effect function to the left, rather than producing
      nonspecific effects or exclusively enhancing the rate-decreasing effects of high
      doses of cocaine. Under fixed-ratio or progressive-ratio schedules, rats were
      allowed to intravenously self-administer cocaine, 7-OH-DPAT, or a combination of
      cocaine and 7-OH-DPAT. In additional tests under fixed-ratio schedules, cocaine
      self-administration followed subcutaneous pretreatment with 7-OH-DPAT. Cocaine
      dose-effect functions were obtained by varying the unit dose of cocaine either
      between test sessions or within a single session. Intravenous 7-OH-DPAT (1-4ug)
      decreased self-administration of the training dose of cocaine (0.25mg) under a
      fixed-ratio schedule, but failed to shift the entire cocaine self-administration
      dose-effect function to the left under fixed-ratio or progressive-ratio
      schedules. 7-OH-DPAT alone maintained i.v. self-administration under these
      schedules, but produced a shallow self-administration dose-effect function,
      relative to cocaine, under the progressive-ratio schedule. In contrast to
      intravenous 7-OH-DPAT, s.c. pretreatment with 7-OH-DPAT (0.1-0.4mg/kg) not only
      decreased self-administration of the training dose of cocaine but also lowered
      the minimum effective dose of cocaine under fixed-ratio schedules, producing a
      shift to the left of the cocaine self-administration dose-effect function; these
      effects were independent of whether the dose of cocaine was varied between
      sessions or within a single session. Likewise under a multiple schedule, in which
      responding was maintained by cocaine and food in alternate components, s.c.
      pretreatment with 7-OH-DPAT increased self-administration of the dose of cocaine
      on the ascending limb of the dose-effect function and decreased self
      administration of doses of cocaine on the descending limb, while uniformly
      decreasing responding for food. These observations suggest that pretreatment with
      7-OH-DPAT enhances the reinforcing properties of cocaine rather than producing
      nonspecific effects or enhancing exclusively the rate-decreasing effects of high
      doses of self-administered cocaine.

PMID- 11224343
TI  - The contribution of within-session averaging of drug- and vehicle-appropriate
      responding to the graded dose-response function in drug discrimination learning.
AB  - Prior work within the taste aversion baseline of drug discrimination learning has
      demonstrated that the generalization function for individual rats is graded in
      nature. In such work, intermediate doses of the training drug produced
      intermediate levels of drug-appropriate responding. Under some conditions, such
      graded responding has been reported to be due to an averaging of quantal drug-
      and vehicle-appropriate responding at different periods within the session. The
      present experiment assessed the contribution of such averaging to the graded
      responding within the aversion design. Rats were first trained to discriminate
      either 1mg/kg naloxone or 10mg/kg pentobarbital from distilled water. They were
      then administered various doses of the training drug (or a different drug), and
      the within-session pattern of licking was monitored minute by minute over the
      20min session. Responding within the session was primarily either drug- or
      vehicle-appropriate. The specific pattern of drug- or vehicle-appropriate
      responding was presumably dependent upon the onset and/or offset of the drug
      stimulus. Thus, for the aversion baseline the graded response function for
      individual rats appears to be a function of the within session averaging of
      quantal (either drug- or vehicle-appropriate) responding.

PMID- 11224344
TI  - Effects of varying ethanol dose on cigarette consumption in healthy normal
      volunteers.
AB  - This study examined the effects of acute doses of ethanol on smoking in cigarette
      smokers. Subjects were moderate to-heavy smokers (20-30 cigarettes/day) who drank
      alcohol regularly (4-10 drinks/week). Using a within-subjects design, the dose of
      ethanol ingested was varied and the number of cigarettes smoked and the temporal
      pattern of smoking were evaluated. At the beginning of the session, subjects
      ingested placebo, 0.2, 0.4, or 0.8g/kg ethanol and were then allowed to smoke
      freely for 3h. Subjective mood measures, physiological measures and psychomotor
      performance were examined at hourly intervals. Subjects smoked more cigarettes
      during the first hour post-beverage after consuming 0.4 or 0.8g/kg ethanol than
      after consuming placebo or 0.2g/kg ethanol. During the second and third hours of
      smoking, no differences were observed between the conditions. Changes in the
      carbon monoxide content of subjects' breath as a function of dose were not
      significant, but were in the expected direction based on the number of cigarettes
      smoked under the different conditions. We conclude that alcohol increases
      cigarette consumption in non-alcohol-abusing smokers, but that this effect is
      short-lived and occurs only during the ascending limb of the blood alcohol curve.

PMID- 11224345
TI  - The failure of cocaine to serve as an orally self-administered reinforcer in
      Lewis rats.
AB  - The aim of this study was to develop a procedure to establish orally delivered
      cocaine as a reinforcer for rats. Several procedures that have proven reliable in
      other studies were instituted. (1) Food-induced drinking: food was presented to
      engender high rates of drinking, then cocaine solutions replaced water, and
      finally the food was removed. Peak drug intakes ranged from 9.4 to 13.8mg/kg. (2)
      Ethanol-fade: ethanol was established as a reinforcer, cocaine was gradually
      added to the ethanol, and the ethanol was gradually removed. Peak cocaine intakes
      ranged from 3.6 to 5.2mg/kg. (3) Modified food-induced drinking: food was
      presented, but was followed by a timeout period, allowing digestion to progress
      prior to cocaine drinking. Peak drug intakes ranged from 12.9 to 18.6mg/kg.
      However, cocaine was not established as a reinforcer with any of these methods.
      High cocaine doses may be necessary, but are not sufficient, to establish oral
      cocaine self-administration in rats.

PMID- 11224346
TI  - Conditioned taste aversions in rats after intracerebral administration of
      nicotine.
AB  - Previous studies suggested that the conditioned taste aversion (CTA) produced by
      nicotine was of central origin. The aims of the present work were to identify
      neural substrates that mediate nicotine-induced CTA, and to examine the
      relationship between the CTA and locomotor depressant effects of nicotine. After
      two conditioning trials with 0.1 or 0.4mg/kg nicotine (s.c.), significant CTA was
      apparent. In contrast, CTA was absent when nicotine (4 or 32ug) was administered
      into a lateral ventricle or when nicotine (4ug) was administered into the fourth
      ventricle, but decreases in locomotor activity were apparent during the
      conditioning phase. Nicotine (8ug) produced CTA when administered bilaterally
      into the nucleus accumbens. This finding was confirmed in a second experiment,
      but was not found in rats pretreated with the nicotine antagonist mecamylamine
      (2mg/kg s.c.). Bilateral administration of nicotine into the striatum, ventral
      tegmental area, dorsal hippocampus or the mesopontine tegmentum failed to produce
      CTA, and administration of nicotine into the interpeduncular nucleus produced CTA
      in one of two experiments only. It was concluded that the aversive effects
      produced by systemically administered nicotine may be mediated in part through
      nicotinic receptors located in the nucleus accumbens. The locomotor depression
      associated with intraventricular administration of nicotine could be dissociated
      from the aversive effect as measured by the CTA procedure.

PMID- 11224347
TI  - Effects of naltrexone pretreatment on the subjective and performance effects of
      ethanol in social drinkers.
AB  - Clinical trials suggest that opioid antagonists may be effective in the treatment
      of alcoholism. For example, two recent clinical trials reported that alcoholics
      treated with the opioid antagonist naltrexone exhibited higher abstinence rates,
      decreased craving and a decrease in the amount of alcohol consumed if drinking
      occurred. The present study examined the hypothesis that naltrexone pretreatment
      would attenuate the behavioral responses to an acute dose of ethanol in normal,
      healthy social drinkers. Thirteen healthy male and female social drinkers
      participated in a six-session, double-blind, placebo-controlled, crossover design
      study. On each session, subjects ingested a capsule containing naltrexone (25 or
      50mg) or placebo and one hour later consumed a beverage containing ethanol
      (0.5g/kg) or placebo. For three hours after the beverage was consumed, breath
      alcohol levels were measured and subjects completed standardized subjective
      effects questionnaires and performance tasks at regular intervals. Ethanol alone
      produced its prototypic effects, including positive subjective responses such as
      euphoria and increased ratings of overall liking, as well as increased ratings of
      confusion. Ethanol also impaired performance on a verbal recall task. Naltrexone
      alone produced few subjective effects and did not impair psychomotor or verbal
      recall performance. Contrary to our hypothesis, pretreatment with naltrexone did
      not alter the positive subjective effects, or any other effects, of ethanol.
      Further research is needed to determine the influence of factors such as baseline
      level of ethanol consumption or duration of naltrexone treatment on the
      interaction between ethanol and the endogenous opioid system.

PMID- 11224348
TI  - Local pharmacological manipulations of prefrontal dopamine affect conflict
      behaviour in rats.
AB  - Several lines of research have implicated the prefrontal cortex (PFC) and its
      dopaminergic (DA) innervation in an animal's response to stress and anxiety. To
      extend these findings we evaluated the effects of bilateral infusions of DA drugs
      into the medial PFC of rats, in a modified conflict test, consisting of Reward,
      Conflict and Time-out components. In experiment 1, the effects of infusions of
      the DA receptor agonist apomorphine (APO) were compared to the effects of
      systemic injections of the same drug. APO infusions induced a dose-dependent
      decrease of responding in the Conflict component, indicative of an anxiogenic
      like effect. However, response rates in the Reward component were simultaneously
      decreased, casting some doubt on the specificity of the effect. In comparison,
      i.p injections of APO in a second group of animals did not affect responding in
      the Conflict component, but dose-dependently decreased response rates during Time
      out and Reward components. In experiment 2, we evaluated the effects of infusions
      of APO and the DA receptor antagonist cis-flupenthixol (FLU) into the medial PFC
      in the conflict test, and in one of its variants, the extinction of conflict
      test. Although both APO and FLU decreased response rates during Reward
      components, responding in the Conflict components of both tests was
      differentially affected. APO infusions decreased Conflict responses, the effect
      being more pronounced in the extinction of conflict test. In contrast, infusions
      of FLU increased responding in the Conflict components. The respective pro- and
      anti-conflict effects of APO and FLU infusions are in favour of a direct
      involvement of prefrontal DA in anxiety-related behavioural responses.

PMID- 11224349
TI  - Provocation frequency and its role in determining the effects of smoked marijuana
      on human aggressive responding.
AB  - Five male subjects participated in an experiment to determine how variations in
      provocation frequency, manipulated before and after smoking marijuana, would
      affect free-operant aggressive responding. Two response buttons, A and B, were
      available. Pressing button A was maintained by a fixed-ratio 100 schedule of
      point presentation. Subjects were instructed that the completion of each fixed
      ratio 10 on button B resulted in a point subtraction from a second subject (who
      was in fact fictitious). Button B responses were defined as aggressive, since
      they ostensibly resulted in the presentation of an aversive stimulus (i.e., point
      subtraction) to another person. Aggressive responding was engendered by a random
      time schedule of point subtraction and maintained by the initiation of intervals
      free from point subtraction. Points subtracted from the subjects were attributed
      to the fictitious other subject. The effects of smoking placebo and 3.58% w/w
      Delta-9-tetrahydro-canabinol marijuana cigarettes, on aggressive responding under
      four different provocation conditions, were studied: (1) low provocation before
      and low provocation after smoking; (2) low provocation before and high
      provocation after smoking; (3) high provocation before and low provocation after
      smoking; and (4) high provocation before and after smoking. Manipulating the
      level of provocation frequency immediately before smoking marijuana had no effect
      on the number of aggressive responses emitted after smoking marijuana. Rather,
      the provocation frequency immediately after smoking marijuana was important.
      After smoking active marijuana cigarettes, aggressive responding was
      significantly suppressed, relative to placebo, under the high provocation
      condition but not under the low provocation condition. As a result, the effects
      of marijuana on aggression appear to be largely determined by the environmental
      conditions (i.e., level of provocation frequency and/or rate of aggressive
      responding) present immediately after smoking marijuana. This finding may help to
      account for some of the inconsistencies observed in previous studies, where
      marijuana has been found to both increase and decrease aggressive responding.

PMID- 11224350
TI  - Involvement of 5-HT(1A) and 5-HT(2) receptors of the inferior colliculus in
      aversive states induced by exposure of rats to the elevated plus-maze test.
AB  - Much evidence has shown that the inferior colliculus may be part of a brain
      system commanding defensive behavior. In the present work, evidence is presented
      for the serotonergic modulation of the neural substrate of aversive states
      elaborated in this structure. Rats implanted with a cannula in the inferior
      colliculus were tested on the elevated plus-maze. Microinjections of zimeldine, a
      5-HT uptake blocker, produced increases in the percentage of open arm entries and
      time spent on the open arms. 8-OH-DPAT, a 5-HT(1A) agonist, and alpha-methyl-5
      hydroxytryptamine, a highly selective 5-HT(2) agonist, injected directly into the
      inferior colliculus also produced clear anxiolytic-like effects in a dose
      dependent manner. Based on these results we suggest that pharmacological
      interference with 5-HT mechanisms in the inferior colliculus may produce
      antiaversive effects.

PMID- 11224352
TI  - Glutamate receptors in neuroadaptation and benzodiazepine tolerance and
      dependence. Commentary on Stephens. 'A glutamatergic hypothesis of drug
      dependence: extrapolations from benzodiazepine receptor ligands'

PMID- 11224351
TI  - A glutamatergic hypothesis of drug dependence: extrapolations from benzodiazepine
      receptor ligands.
AB  - This article explores some of the data available on processes underlying
      dependence and withdrawal following chronic treatment with substances acting at
      GABA(A) receptors. It is argued that adaptations arising from chronic treatment
      with benzodiazepines (BZs) and ethanol, on the one hand, and inverse agonists at
      BZ receptors, on the other, cannot be explained by changes primarily in GABAergic
      systems, and that compensatory changes in glutamatergic transmission account at
      least partially for tolerance to, and dependence on, BZs and ethanol. The
      literature on ethanol dependence also points to sensitisation following repeated
      withdrawals (i.e. increasing intensity of certain withdrawal symptoms and signs)
      as a potentially important factor in ethanol dependence. It is predicted that a
      similar sensitisation may also result from repeated BZ withdrawal. In the case of
      ethanol, this kindling-like process is also dependent on glutamatergic
      neurotransmission. Parallels are drawn between changes underlying the increase in
      sensitivity to repeated withdrawal and kindling to BZ receptor inverse agonists.
      The involvement of glutamatergic mechanisms in the development of tolerance to
      and dependence on other abused drugs is also explored. The role of glutamate in
      the development of behavioural sensitisation to psychomotor stimulants and other
      abused drugs is addressed, and the possibility raised that similar processes may
      be involved in both behavioural sensitisation and withdrawal sensitisation.

PMID- 11224353
TI  - Can EAA transmission play a ubiquitous role in drug-induced neural plasticity?
      Commentary on Stephens, 'A glutamatergic hypothesis of drug dependence:
      extrapolations from benzodiazepine receptor ligands'

PMID- 11224354
TI  - Modulation of learning processes by ionotropic glutamate receptor ligands.
AB  - A great body of evidence has been provided for the role of N-methyl-d-aspartate
      (NMDA) receptors in learning processes, since the pioneering work of Morris et
      al. (1986) showing impairment of water maze learning and long-term potentiation
      (LTP) during i.c.v. infusion of the NMDA receptor antagonst 2-amino-5
      phosphonovaleric acid (AP5). The existing literature, based on pharmacological
      studies, suggests the importance of NMDA receptors for the acquisition and/or the
      initial phase of long-term memory consolidation in many, but not all, learning
      paradigms. Data on short-term memory are inconsistent, probably due to
      difficulties in separation of learning deficits from performance. Although it is
      generally accepted that NMDA receptor antagonists impair learning, more recent
      data suggest that, under certain conditions, the opposite effect, enhancement of
      learning, can be obtained. The role of alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid (AMPA) receptors in learning, although accepted in LTP, is less
      well documented. It has been suggested that positive modulation of these
      receptors could result in cognitive enhancement that might find therapeutic
      application. The present paper reviews the literature dealing with these issues
      and discusses possible consequences for the therapy of dementia.

PMID- 11224355
TI  - How do glutamateric drugs affect cognitive function? Commentary on Danysz et al.,
      'Modulation of learning processes by ionotropic glutamate receptor ligands'

PMID- 11224356
TI  - Interactions between excitatory amino acids and dopamine systems in the
      forebrain: implications for schizophrenia and Parkinson's disease.
AB  - The midbrain dopamine neurones innervate not only the dorsal and ventral sectors
      of the striatum but also limbic structures and fronto-temporal association
      cortex. The forebrain structures providing and receiving dopaminergic input are
      highly interconnected. The dopamine pathways are now seen to provide modulation
      of widespread limbo- and cortico-striatal circuits involved in motivated
      behaviour. The nucleus accumbens is a pivotal structure of this ventral striatal
      system, whereas the caudate putamen of the dorsal striatum integrates sensori
      motor coordination. These striatal sectors have access to complex parallel output
      pathways of the pallidal and the thalamo-cortical motor systems. Excitatory amino
      acids are now known to play an important role as neurotransmitters in the dorsal
      and ventral forebrain circuits and in the output pathways associated with
      dopamine neurones. Current drug treatment of both schizophrenia and Parkinson's
      disease focus on drugs which modify dopamine activity in the brain. Glutamatergic
      mechanisms may provide interesting alternative pharmacological targets for the
      treatment of such disorders.

PMID- 11224357
TI  - Reversal of parkinsonian symptoms by intrastriatal and systemic manipulations of
      excitatory amino acid and dopamine transmission in the bilateral 6-OHDA lesioned
      marmoset.
AB  - We have investigated the potential of alleviating parkinsonian symptoms by
      manipulating excitatory amino acid (EAA) transmission, by several different
      pharmacological means, in a novel primate model of parkinsonism. The model is
      based on a two-stage bilateral 6-hydroxydopamine lesion procedure in marmosets,
      which produces a stable but marked parkinsonian condition. Parkinsonian symptoms
      were reversed in a dose-dependent manner by systemic administration of levodopa
      and intrastriatal injections of apomorphine administered into either the caudate
      nucleus or the putamen. (R)-HA-966, a partial agonist for the NMDA receptor
      associated glycine site, also alleviated parkinsonian symptoms when injected
      intrastriatally but not when injected systemically. Systemic injection of
      enadoline, a kappa opiate which blocks release of EAAs, reduced parkinsonian
      symptoms when injected systemically, though it did not restore completely normal
      motor behaviour. In contrast, ifenprodil, an antagonist for the NMDA receptor
      associated polyamine modulatory site, when injected systemically at an optimal
      dose, resulted in apparently normal motor behaviour. These data suggest that
      attenuation of EAA transmission could be used to treat parkinsonism.

PMID- 11224358
TI  - Does the blockade of excitatory amino acid transmission in the basal ganglia
      simply reverse reaction time deficits induced by dopamine inactivation?
AB  - It has recently been hypothesized that excessive excitatory amino acid (EAA)
      activity in the corticostriatal pathway and in the subthalamic nucleus could
      account for the expression of the motor deficits resulting from alteration in
      dopamine function in the basal ganglia. The present study investigated the
      potential benefit of blocking excitatory amino acid transmission in the basal
      ganglia, subsequent to the inactivation of dopaminergic function of rats
      performing a reaction time (RT) task. Disruption of dopamine activity by the
      neurotoxin 6-hydroxydopamine (6-OHDA) injected in the striatum or by systemic
      administration of the D2 dopamine receptor antagonist raclopride, impaired the
      performance of rats trained to release a lever quickly after a visual stimulus.
      RTs, measured by the time elapsing from the stimulus onset to the lever release,
      were lengthened after both treatments. The blockade of EAA transmission at the N
      methyl-D-aspartate (NMDA) receptor, by systemic injections of the NMDA receptor
      antagonist dizocilpine or by excitotoxic lesions of the subthalamic nucleus, in
      animals with dopamine lesions, significantly reversed the increase of RTs.
      Performance of animals with subthalamic nucleus lesions did not return to pre
      operative values, however. The blockade of NMDA receptors in the striatum, by a
      local injection of the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric
      acid (APV), in animals treated with raclopride, was found to decrease RTs and
      improve performance. Analysis of RT distributions in the three groups of animals
      revealed that blocking EAA activity with NMDA receptor antagonists improved
      performance by shifting RTs back towards baseline values, preserving a normal
      distribution. In contrast, lesions of the subthalamic nucleus disrupted
      performance, as shown by the scattered distribution of RTs. The results indicate
      that treatment with NMDA receptor antagonists but not subthalamotomy provides a
      possible beneficial treatment in the present model of Parkinsonism.

PMID- 11224359
TI  - The anti-ischaemic drug, eliprodil, blocks hyperactivity induced by intra
      accumbens injection of spermine.
AB  - NMDA receptor mechanisms in the nucleus accumbens play an important role in the
      control of locomotor activity. Among the several binding sites associated with
      these receptors, the polyamine-sensitive sites have received relatively little
      attention. It has recently been shown, however, that the anti-ischaemic drug
      eliprodil NMDA antagonist effects probably mediated by activity at this polyamine
      site. In the present series of experiments the effects of injections of spermine
      and eliprodil into the nucleus accumbens of rats were investigated. Locomotor
      hyperactivity was produced by intra-accumbens injection of spermine,
      phencyclidine and AP7. Phencyclidine, but not AP7, produced a similar effect
      after systemic injection. Eliprodil did not increase locomotion after either
      intra-accumbens or i.p. administration. However, systemic injection of eliprodil
      (5, 10, 20mg/kg) produced a dose-related antagonism of hyperactivity induced by
      intra-accumbens spermine, but not by systemic or intra-accumbens injection of d
      amphetamine. These results provide the first behavioural demonstration of the
      polyamine antagonist properties of eliprodil, and further emphasise the
      differences between the pharmacological profile of eliprodil and those of other
      NMDA antagonists.

PMID- 11224360
TI  - Excitatory amino acid receptors within nucleus accumbens subregions
      differentially mediate spatial learning in the rat.
AB  - The present experiments investigated the effects of excitatory amino acid
      antagonists, infused into core and shell subregions of the nucleus accumbens, on
      spatial behavior in the rat. A food-search task was used, in which animals learn
      a specific pattern of food gathering; duration of each trial (time taken to
      gather all four pellets) and number of errors (visits to empty holes) were
      measured. In experiment 1, animals first underwent training, and subsequently
      were given microinfusions of either D-2-amino-5 phosphonopentanoic acid (AP-5),
      an N-methyl-d-aspartate (NMDA) antagonist (0, 0.2, 1.0ug/0.5ul), or 6,7
      dinitroquinoxaline-2,3-dione (DNQX), an antagonist of alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid (AMPA) and kainate receptors (0, 0.075,
      0.75ug/0.5ul). AP-5-significantly increased trial duration in both core and shell
      groups, but increased errors only in the core group. DNQX treatment also impaired
      performance in both groups, but the effect was greater in the core group compared
      with the shell group. In experiment 2, animals were treated during acquisition.
      Rats infused with AP-5 (1ug/0.5ul) took significantly longer to finish trials,
      made more errors and showed a marked learning impairment across days. AP-5
      impaired learning in both core and shell groups, but the disruption was
      significantly greater in the core group. DNQX (0.75ug/0.5ul) also impaired
      learning when infused into the core during acquisition; however, the pattern of
      disruption contrasted markedly with that of AP-5. DNQX in the shell had no effect
      on trial duration during learning. It is hypothesized that both NMDA and non-NMDA
      receptors in the nucleus accumbens mediate spatial learning and performance, and
      that NMDA receptors may have a relatively more important role in memory or
      retrieval mechanisms. Moreover, the core subregion may be preferentially involved
      in the control of spatial behavior.

PMID- 11224361
TI  - The effect of dizocilpine (MK-801) on spatial and visual discrimination tasks in
      the rat.
AB  - The present experiments investigated the effect of the non-competitive N-methyl-d
      aspartate (NMDA)-receptor antagonist, dizocilpine (MK-801) (0.075mg/kg) on
      acquisition and reversal of either a spatial or a visual, appetitively rewarded,
      simultaneous discrimination task in a Y-maze. The experimental design for the
      spatial and the visual discriminations was identical, the only difference between
      the tasks being the nature of the stimulus. Dizocilpine had not effect on
      acquisition of the spatial task although, when this task was reversed,
      dizocilpine-treated rats took significantly more trials to reach criterion. On
      the visual task, dizocilpine impaired both acquisition and reversal. Thus,
      systemic administration of dizocilpine did not produce a specific spatial
      learning impairment. The fact that dizocilpine impaired reversal but not
      acquisition in the spatial task argues against a global performance deficit.
      Although both the acquisition and reversal phases of the experiment make equal
      sensory and motor demands on the animal, reversal involves specific learning
      processes that may be disrupted by dizocilpine.

PMID- 11224362
TI  - Comparison of glutamate antagonists in continuous multiple-trial and single-trial
      dark avoidance.
AB  - NMDA receptor antagonists (MK-801, memantine, amantadine, CGP37849), and the AMPA
      receptor antagonist NBQX, were tested in a continuous multiple-trial two-choice
      dark avoidance paradigm. During training MK-801 (0.2mg/kg) and CGP-37849
      (12mg/kg) increased the number of trials to criterion. Amantadine (92mg/kg)
      increased all parameters except the number of trials to criterion. CGP37849 (6
      and 12mg/kg) increased the number of shocks per trial. Injection of MK-801
      (0.2mg/kg), memantine (20mg/kg), amantadine (92mg/kg) or CGP37849 (6 or 12mg/kg)
      before training decreased the latency to enter the dark compartment in the
      retention test 24h later. NBQX affected neither training nor retention
      parameters. NMDA antagonists were also tested in a single-trial two-choice dark
      avoidance procedure. Pre-training but not pre-retention test injection of MK-801
      (0.2mg/kg), memantine (20mg/kg), amantadine (92mg/kg) or CGP37849 (12mg/kg)
      decreased the latency to enter the dark compartment during retention; scopolamine
      had similar effects. Hence, NMDA receptor antagonists, but not the AMPA receptor
      antagonist NBQX, impair memory storage which is also seen in animals trained to
      criterion, indicating that interference with the acquisition processes is not
      solely responsible for the memory deficit. This deficit occurs at doses that do
      not appear to interfere with the recall and the performance of the previously
      learned response.

PMID- 11224363
TI  - Reversal of stable behavioural modifications through NMDA receptor inhibition in
      rats.
AB  - In order to study the effect of long-term dizocilpine infusion on memory, two
      different paradigms of stably modified behaviour were used in rats. The first was
      the escape deficits (ED) induced and maintained either by repeated daily
      administrations of SKF 38393, a rather selective D1 dopamine receptor agonist, or
      by repeated stress; the second was sensitisation to the effect of cocaine on
      motility. Fluoxetine (FLX), imipramine (IMI) and clomipramine (CMI) were equally
      effective in reversing the reduced reactivity of animals in both ED models.
      Dizocilpine showed a similar efficacy to that of classic antidepressants on the
      pharmacologically-induced ED, but failed to affect the stress-induced ED. In rats
      previously sensitised to cocaine and then infused with dizocilpine for 7 days
      after suspension of cocaine administration, the state of sensitisation, remained
      intact; however, in animals receiving dizocilpine plus a concomitant daily
      injection of cocaine, dizocilpine significantly reduced cocaine sensitisation.
      These results potentially suggest a new approach to the treatment of drug
      addiction and other psychiatric disorders. Finally, it was concluded that NMDA
      receptor blockade not only prevents, but also reverses many, if not all, learned
      behaviours, and that this phenomenon differs from the effect of antidepressants.

PMID- 11224364
TI  - Behavioral studies with the glycine partial agonist (+)-HA966 on cocaine-induced
      locomotor activity and reinforcement.
AB  - Recent evidence suggests that excitatory amino acids may play a critical role in
      the mediation of the behavioral effects of cocaine. The present experiments were
      designed to examine the effects of the glycine-site partial agonist (+)-HA966, a
      compound modulating NMDA receptor function, on the development of sensitization
      the locomotor activating effects of cocaine and on intravenous cocaine self
      administration. After chronic cocaine pretreatment (20mg/kg i.p. daily for 3
      days), Sprague-Dawley rats showed much greater increases in activity after a
      cocaine challenge (20mg/kg i.p.) than did saline-pretreated controls. This
      sensitized response was diminished by (+)-HA966 (30, 100 and 200ug), when
      administered intraventricularly (i.c.v.) 5min before each of the three cocaine
      pretreatment injections. (+)-HA966 when given alone for 3 days did not
      significantly diminish subsequent cocaine-induced locomotor activity. However, a
      small dose of (+)-HA966 (30ug) potentiated the acute stimulatory effects of
      cocaine on locomotor activity; higher doses were without effect. With limited
      daily access to intravenous cocaine (0.33mg/kg/infusion), rats showed reliable
      patterns of self-administration under a fixed-ratio 3 (FR3) schedule of
      reinforcement. Pretreatment with small doses of (+)-HA966 administered 5min prior
      to cocaine self-administration sessions had little effect. However, larger doses
      (100 and 200ug i.c.v.) significantly decreased responding. This effect was
      selective, since similar doses produced significantly less suppression of operant
      responding for food. The non-competitive NMDA receptor antagonist, dizocilpine
      (0.03-0.3mg/kg i.p.) administered 30min prior to sessions, significantly
      decreased cocaine self-administration without modifying behavior maintained by
      food. The present findings demonstrate that modulation of NMDA systems can
      significantly modify the behavioral effects of cocaine.

PMID- 11224365
TI  - Behavioral pharmacology of two novel substituted quinoxalinedione glutamate
      antagonists.
AB  - Two novel quinoxalinedione glutamatergic antagonists, with in vitro selectivity
      for the glycine modulatory site on the N-methyl-d-aspartate (NMDA) receptor, were
      evaluated in a number of behavioral tests primarily designed to compare their
      effects to those of the noncompetitive NMDA antagonist phencyclidine (PCP). The
      compounds evaluated were 5-chloro-7-trifluoromethyl-1,4-dihydro-2,3
      quinoxalinedione (ACEA-1011) and 5-nitro-6,7-dichloro-1,4-dihydro-2,3
      quinoxalinedione (ACEA-1021). In rats, both ACEA-1011 and ACEA-1021 were
      completely devoid of PCP-like discriminative stimulus effects, although
      behavioral activity, in the form of response rate suppression, was seen at the
      higher doses tested (6-25mg/kg, i.p.). ACEA-1011 and ACEA-1021 were also
      ineffective as antagonists of PCP discrimination in rats. ACEA-1021 failed to
      substitute in rhesus monkeys trained to discriminate PCP from sham injection,
      although in the monkeys minimal effects were observed on rates of responding even
      at the highest dose tested (10.2mg/kg, i.v.). ACEA-1021 also failed to produce
      ethanol-like discriminative stimulus effects in rats under test conditions where
      PCP has been shown to produce substantial levels of substitution for ethanol.
      Both ACEA-1011 and ACEA-1021 were also evaluated as antagonists of NMDA
      discrimination in rats. ACEA-1011 produced some decreases in NMDA-lever
      responding, with the largest effect at one intermediate dose (3mg/kg, i.p.). ACEA
      1021 was ineffective as an antagonist of NMDA discrimination. Unlike results
      reported for PCP-like NMDA antagonists, neither ACEA-1011 nor ACEA-1021 disrupted
      prepulse inhibition of the acoustic startle reflex in rats. It was not possible
      to establish ACEA-1021 (10 or 15.6mg/kg) as a discriminative stimulus in rats. In
      conclusion, the novel glutamate antagonists ACEA-1011 and ACEA-1021 did not
      produce a profile of behavioral effects similar to that of PCP-like
      noncompetitive NMDA antagonists. These results are consistent with an emerging
      body of evidence showing differences in the behavioral effects of different
      classes of glutamate antagonists.

PMID- 11224366
TI  - Effects of the NMDA antagonist, dizocilpine, in various drug discriminations:
      characterization of intermediate levels of drug lever selection.
AB  - In each of different groups of rats trained to discriminate either 8-OH-DPAT,
      DOI, d-amphetamine, cocaine, chlordiazepoide or ethanol from saline, dizocilpine
      produced maximum percentages of drug lever (DL) selection that were intermediate
      between those produced by the training conditions. Dizocilpine also decreased DL
      selection produced by the training dose in each of the discriminations, except in
      ethanol-trained rats. In all discriminations, with the exception of ethanol
      trained rats, the intermediate levels of DL, selection produced by dizocilpine
      were associated with increased FRF values (sum of the responses made on either
      lever before the first reinforcement occurred), increased lever selection
      latencies, and increased responding on the nonselected lever. At doses that, in
      general, had effects on response rate similar to those of dizocilpine,
      intermediate levels of DL selection were produced by BMY 7378 in 8-OH-DPAT
      trained rats, by WY 50,324 in DOI-trained rats, by (-)-3-PPP in d-amphetamine-
      and in cocaine-trained rats, by alpidem in chlordiazepoxide-trained rats, and by
      PCP in ethanol-trained rats. The intermediate levels of DL selection produced by
      these latter drugs were not associated with simultaneous increases of FRF values,
      selection latencies, and responding on the nonselected lever. The results suggest
      that dizocilpine produces intermediate levels of drug-appropriate responding
      through the behavioral mechanism of partial generalization only in ethanol
      trained rats; in all other discriminations examined here, the effects of
      dizocilpine appear to involve (1) pharmacological effects that differ from those
      of the training drug, and (2) behavioral mechanisms that are unrelated to
      stimulus generalization. The differentiation of partial generalization and other
      mechanisms whereby intermediate responding can occur in the drug discrimination
      paradigm requires analyses that are more detailed than those commonly used in
      drug discrimination research.

PMID- 11224367
TI  - Assessment of the mixed discriminative stimulus effects of ethanol in a three
      choice ethanol-dizocilpine-water discrimination in rats.
AB  - Previous drug discrimination studies have elucidated the importance of the NMDA,
      GABA(A) and 5-HT(1) receptor systems in mediating the discriminative stimulus
      effects of ethanol. The present study used a three-choice drug discrimination
      paradigm in an attempt to determine whether the salient NMDA antagonistic effects
      were separable from other stimulus effects of ethanol. Adult Long-Evans rats (n =
      7) were trained to discriminate ethanol (1.5g/kg, intragastric (i.g.)), the
      uncompetitive NMDA antagonist dizocilpine (0.17mg/kg, i.g.) or water (3.5ml,
      i.g.) under a food-reinforced fixed-ratio 15 (FR15) schedule of reinforcement.
      Following training, substitution tests were conducted with the
      GABA(A)/benzodiazepine (GABA(A)/BDZ) positive modulator pentobarbital (PB, 5.6
      17mg/kg, i.g.), the uncompetitive NMDA antagonist phenycldine (PCP, 0.1-5.6mg/kg,
      i.p.) and the 5-HT(1) agonist RU 24969 (0.1-3.0mg/kg, i.p.). Complete
      substitution of PCP (ED(50), 0.9mg/kg) for dizocilpine was found in all animals.
      Conversely, PB (ED(50), 10mg/kg) substituted fully for ethanol in five of seven
      animals, whereas RU 24969 (ED(50), 1.4mg/kg) completely substituted for ethanol
      in only three of seven animals tested. The result demonstrate that a three-choice
      discrimination using dizocilpine, ethanol and water as training conditions can be
      established in rats. By contrasting the discriminative stimulus effects of an
      uncompetitive NMDA antagonist to ethanol, the ethanol-like effects of
      pentobarbital and RU 24969 are attenuated compared to previous studies of two
      choice ethanol water discrimination.

PMID- 11224368
TI  - A bibliography of drug discrimination research, 1992-1994.
AB  - The major content of this publication is a comprehensive bibliography of research
      into the discriminative stimulus effects of drugs in animal and human subjects
      for the period 1991-1994. The bibliography is accompanied by a detailed cross
      index that facilitates access to this literature through keywords based on the
      drugs studied, how the drugs were used, and numerous other methodological
      variables such as species of subject and schedule of reinforcement. The article
      also explains how users may obtain access to the present and earlier versions of
      the database, which are available as computer disks and over the Internet. The
      easy access to this literature made possible by the database should increase the
      working efficiency of the many groups that employ drug discrimination methods and
      should also support dissemination of the knowledge acquired to a wider scientific
      community.

PMID- 11224369
TI  - Pharmacological characterization of an operant discrimination among two doses of
      morphine and saline in pigeons.
AB  - A cumulative dose, multiple-trial test procedure was developed in eight pigeons
      trained to discriminate among saline, 1.8mg/kg morphine, and 10mg/kg morphine.
      Initially, single-trial tests were used to evaluate stimulus effects of acute
      doses of morphine. Next, the test procedure was altered so that cumulative doses
      were tested within a single session. Results from cumulative-dose tests of
      morphine were consistent with those from single-trial tests. The cumulative-dose
      test procedure was then used to characterize the high-dose and low-dose morphine
      training stimuli. The mu agonists etorphine, fentanyl, methadone and morphine
      dose-dependently evoked both low-dose and high-dose morphine-like effects, with a
      similar potency order (etorphine > fentanyl > methadone = morphine). In contrast,
      nalbuphine evoked only low-dose effects, consistent with low efficacy mu agonist
      activity. The kappa opiate U50,488H evoked saline-key responses, whereas the non
      opiate ketamine evoked saline-key responses in the majority of pigeons, but high
      dose and/or low-dose responding in others. Naltrexone dose-dependently
      antagonized both low-dose and high-dose stimulus effects of morphine, but not its
      rate-decreasing effects. Apparent pA(2) values for naltrexone were 7.2 for low
      dose stimulus effects of morphine, and 7.4 for high-dose effects. These
      characteristics suggest that stimulus effects of both low and high training doses
      of morphine are mediated by common, presumably mu opioid, receptor populations.

PMID- 11224370
TI  - Chronic mild stress-induced anhedonia model of depression; sleep abnormalities
      and curative effects of electroshock treatment.
AB  - A core symptom of human depressive disorder is anhedonia, the loss of interest or
      pleasure in daily activities. Anhedonia, measured as subsensitivity to reward,
      can be induced in rats by a regimen of repeated, mild, unpredictable stressors.
      Here, the hedonic state of rats was assessed using an intracranial self
      stimulation (ICSS) procedure. The ICSS frequency threshold was determined before,
      during and after a period of exposure to the stress regimens. After 13 days of
      repeated mild stress, the ICSS threshold was significantly increased, suggesting
      a gradual decrease of sensitivity to reward. This anhedonic state lasted
      throughout the stress period. When stressed anhedonic animals were given
      electroshock treatment, the stress-induced increase in ICSS threshold was rapidly
      and completely reversed. Moreover, biological markers of human depression such as
      reduced latency to the first REM sleep episode or increased time spent in REM
      sleep were also found in electroencephalographic recordings of chronically
      stressed animals. These sleep abnormalities were observed beginning in the second
      week of a three-week stress regimen and progressively disappeared after
      termination of stress. In conclusion, these data provide further evidence
      supporting stress-induced anhedonia in rats as a unique animal model of human
      depression combining convergent elements of biological, etiological,
      symptomatological and therapeutic validity.

PMID- 11224371
TI  - The effect of BIMT 17, a new potential antidepressant, in the forced swimming
      test in mice.
AB  - BIMT 17 inhibits cortical electrical activity through the activation of cortical
      5-HT(1A) receptors combined with the antagonism of 5-HT(2) receptors. The aim of
      this study was to evaluate the potential antidepressant activity of BIMT 17 and
      its mechanism of action by using the forced swimming test in mice. BIMT 17, when
      administered i.p. (16mg/kg), s.c. (8mg/kg) and orally (32mg/kg), increased the
      struggling time in mice forced to swim. With i.p. administration, BIMT 17 did not
      alter locomotor activity. The effect of BIMT 17 seems to be mediated by 5-HT(1A)
      receptors since it was antagonised by WAY 100135 (10mg/kg i.p.), a selective 5
      HT(1A) antagonist. The 5-HT(2) component does not seem to modulate BIMT 17
      activity since the administration of DOI (1mg/kg i.p.), a 5-HT(2A/2C) agonist,
      did not modify the BIMT 17 effect. Antagonism of BIMT 17 was also produced by
      buspirone (30mg/kg p.o.), alpha-methyl-p-tyrosine (250mg/kg i.p.) and sulpiride
      (50mg/kg i.p.) but not by pindolol (20mg/kg i.p.). Neither the reduction of 5-HT
      synthesis brought about by p-chlorophenylalanine nor the selective destruction of
      5-HT containing neurons by 5,7-dihydroxytryptamine reduced the BIMT 17 effect,
      suggesting that BIMT 17 acts postsynaptically in increasing struggling behaviour.

PMID- 11224372
TI  - Effects of selective antagonism or depletion of the cholinergic system on visual
      discrimination performance in rats.
AB  - A two-lever simultaneous visual discrimination task was used to study the effects
      on performance in Long-Evans rats of the muscarinic antagonists scopolamine
      (0.0125, 0.05, 0.2 and 0.8mg/kg s.c.), the M(1) antagonist pirenzepine, the M(2)
      antagonist AF-DX 116, the M(3) antagonist UH-AH 37 (each 3.2, 10, 32ug/rat,
      i.c.v.), and the cholinergic depleting agent, hemicholinium-3 (0.04, 0.2, 1.0 and
      5.0ug/rat i.c.v.). Scopolamine dose-dependently decreased accuracy, increased the
      number of trials on which the rats failed to respond, and significantly
      lengthened latency to respond. Only the highest doses of hemicholinium-3,
      pirenzepine and AF-DX 116 reduced accuracy and increased errors of omission as
      well as response latency. UH-AH 37 reduced overall task performance at 10 and
      32ug, suggesting that antagonism of both M(3) and other muscarinic receptors
      (including M(1)) had a greater effect on performance than selective antagonism of
      the M(1) or M(2) receptors. These data indicate that the disruptive effects of
      cholinergic antagonism on attentionally demanding tasks are strengthened by
      activity at multiple subtypes of the receptor.

PMID- 11224373
TI  - Examination of the kappa agonist and antagonist properties of opioids in the rat
      drug discrimination procedure: influence of training dose and intrinsic efficacy.
AB  - In a two-choice drug discrimination procedure, rats were trained to discriminate
      either 0.056 (low dose) or 0.17 (high dose) mg/kg of the kappa opioid bremazocine
      from saline. Substitution and antagonism tests were then conducted with a variety
      of opioids. The opioids U50, 488, ethylketocyclazocine, spiradoline, enadoline,
      and U69,593 substituted completely (>/=80% bremazocine-appropriate responding)
      for the bremazocine stimulus in both training groups, a finding consistent with
      their high-efficacy kappa profile. In contrast, the other opioids examined could
      be classified into different subsets on the basis of their patterns of
      substitution and antagonism: (1) (-)-cyclazocine substituted completely for the
      low-dose bremazocine stimulus and substituted partially (approximately 50%
      bremazocine-appropriate responding) for, and antagonized partially, the high-dose
      bremazocine stimulus; (2) butorphanol, nalorphine and nalbuphine substituted
      partially for, and antagonized partially, the low- and high-dose bremazocine
      stimuli; (3) levellorphan did not substitute for either training dose of
      bremazocine and antagonized the bremazocine stimulus at both training doses; (4)
      (-)-N-allylnormetazocine [(-)-NANM] substituted partially for the low-dose
      bremazocine stimulus and substituted completely for the high-dose bremazocine
      stimuli. Despite the high levels of substitution, (-)-NANM antagonized both the
      low- and high-dose bremazocine stimuli at doses below those required to produce
      its maximal agonist effects. The substitution patterns exhibited by (-)-NANM were
      not antagonized by doses of naloxone that antagonized the stimulus effects of (-)
      cyclazocine and bremazocine, suggesting that these substitution patterns were non
      opioid mediated. Collectively, these results suggest that the different patterns
      of substitution and antagonism observed with these opioids were due either to
      differences in their intrinsic efficacy at the kappa receptor or to a non-opioid
      component of action.

PMID- 11224374
TI  - Differential ethanol intake in high and low responders to novelty.
AB  - The aim of the study was to determine whether high responders (HR) and low
      responders (LR) to novelty, selected from an outbred Wistar rat population, show
      differences in ethanol consumption. HR and LR differ in catecholaminergic
      activity in the nucleus accumbens as well as in brain sensitivity to
      corticosteroids, biological features believed to play a role in ethanol
      consumption. Due to these differences it was predicted that HR would consume less
      ethanol and show less preference than would LR. Animals were maintained on a
      schedule of alternative day presentation of ethanol. Starting with an ethanol
      presentation of 2% in a free choice with water, ethanol solutions were presented
      and increased by increments of 1% every second day. HR showed a preference for
      water over ethanol, whereas LR showed no preference for water over ethanol. In
      order to determine intake and preference stability, animals were switched to
      daily presentations of ethanol and maintained on a 10% ethanol solution for 18
      days. Individual-specific differences remained stable throughout the entire
      period. Given the available knowledge about biological differences between HR and
      LR, the present data indicate that these animals are good models for the study of
      the mechanisms underlying individual-specific differences in the behavioral
      responses to ethanol.

PMID- 11224375
TI  - Effects of food deprivation and satiation on sensitivity to the discriminative
      stimulus effects of pentobarbital in pigeons and morphine in rats.
AB  - Food deprivation can produce a substantial increase in the self-administration of
      drugs of abuse, suggesting that food deprivation increases their reinforcing
      properties. This finding has been replicated with a wide variety of reinforcing
      drugs. The present experiments examined the effects of food deprivation and
      satiation on the discriminative stimulus properties of drugs, to determine
      whether food deprivation affects the discriminative-stimulus effects of drugs in
      a similar manner. Using pigeons that were trained to discriminate 5mg/kg i.m.
      pentobarbital from saline, dose-effect curves were determined under both food
      deprivation conditions (80% free-feeding body weight) and partial food-satiation
      conditions (25% and 50% of the amount of full satiation). It was found that
      generalization curves for both pentobarbital and saline were similar at all
      levels of food deprivation. In a second set of experiments, rats were trained to
      discriminate 10mg/kg i.p. morphine from saline, and the discriminative properties
      of morphine were then tested when the animals were either food-deprived or after
      a 15min supplemental feeding. The ED(50) value for the food-deprived condition
      was comparable to that the food-satiated condition (3.6 vs. 4.8mg/kg,
      respectively). Thus, in both pigeons and rats, there was little evidence that
      food deprivation increased sensitivity to the discriminative stimulus properties
      of drugs. Thus, food deprivation must increase drug self-administration by a
      mechanism other than by increasing the discriminative stimulus properties of self
      administered drugs.

PMID- 11224376
TI  - A model of 'antipredator' defense in Swiss-Webster mice: effects of
      benzodiazepine receptor ligands with different intrinsic activities.
AB  - A mouse defense test battery (MDTB) has been designed to assess defensive
      reactions of Swiss-Webster mice to situations associated with nonpainful threat.
      When compared to mice approached by a leather glove, animals confronted with an
      anesthetized or a conscious rat displayed potentiated flight responses and
      defensive threat/attack reactions, while risk assessment performances were
      generally similar in all three conditions. Furthermore, escape attempt responses
      following removal of the stimulus were higher in the conscious rat condition
      compared to the two other groups. Taken together, these results suggest that
      flight reactions and defensive threat/attack responses are specific to the rat,
      and thus indicate that the MDTB may relate to 'antipredator' defense. In mice
      confronted with an anaesthetized rat, administration of the benzodiazepine (BZ)
      receptor full agonist chlordiazepoxide (5-25mg/kg, i.p., 30min) and the BZ
      partial agonist Ro 19-8022 (0.5-2mg/kg, i.p., 30min) altered one of two risk
      assessment measures and inhibited defensive attack behaviors, but failed to
      counter the post-predator increase in escape attempts. In addition, Ro 19-8022
      also strongly reduced flight responses. The overall behavioral profile suggests a
      fear/anxiety-reducing action of both drugs. By contrast, administration of the BZ
      inverse agonist Ro 19-4603 (0.025-0.1mg/kg, i.p., 30min) reliably released these
      defensive responses. Interestingly, the BZ antagonist flumazenil (5-20mg/kg,
      i.p., 30min) manifested differential intrinsic activity depending upon the level
      of threat. Thus, in a weakly threatening situation, the drug potentiated flight
      reactions, indicating an inverse agonist-like action, decreased defensive biting
      in a highly threatening situation, indicating an agonist activity. These findings
      demonstrated that BZ ligands differently modulated 'antipredator' defense in
      Swiss-Webster mice, depending upon their intrinsic (positive or negative)
      efficacy, but also depending upon the defense strategy required by the threat.

PMID- 11224377
TI  - Effects of acute and chronic cocaine on milk intake, body weight, and activity in
      bottle- and cannula-fed rats.
AB  - The effects of cocaine on the milk intake, body weight and activity of bottle-
      and cannula-fed rats was compared under both acute and chronic dosing conditions.
      Bottle-fed rats were initially more hypophagic than cannula-fed rats when given
      acute injections of cocaine (4-40mg/kg). Following chronic injections of the drug
      (16mg/kg), bottle-fed rats developed tolerance, as shown by a rightward shift in
      the dose-response function for milk intake. Such tolerance was accompanied by a
      decrease in drug-induced motor activity. In contrast, cannula-fed rats showed
      marked sensitization of stereotyped movements. Bottle -fed rats showed marked
      sensitization of stereotyped movements. However, weight loss per se was not a
      determining factor in tolerance development, because cannula-fed rats given
      chronic injections of 32mg/kg cocaine lost even more weight, but did not become
      tolerant. These results suggest that, at moderate doses, cocaine suppresses
      feeding primarily by inducing behaviors that are incompatible with the appetitive
      phase of feeding, and that tolerance involves learning to inhibit such responses
      in order to feed.

PMID- 11224378
TI  - Effects of response cost and unit dose on alcohol self-administration in moderate
      drinkers.
AB  - Alcohol self-administration by nonhumans and alcoholic humans decreases as the
      response requirement to obtain the drug increases. Also, increases in dose or
      concentration of alcohol, increase consumption up to a maximum in these
      populations, after which further increases in dose decrease intake. In the
      present study, the effects of response cost and dose on alcohol self
      administration were investigated in moderate drinkers (12-45 drinks/week). Three
      male volunteers self-administered alcohol (commercial beer) during 2h sessions
      twice weekly. Alcohol was available under a fixed-ratio (FR) schedule of
      reinforcement. Response requirement (FR100-1600) and dose (2 and 4oz of beer)
      were varied separately across sessions using a within-subjects design. As
      response cost increased, consumption and overall rates of responding generally
      changed in an inverted U-shaped manner. Maximal consumption was observed at the
      4oz dose. These orderly relations between response cost, dose and alcohol self
      administration extend prior findings in nonhumans and alcoholics to moderate
      drinkers. Such consistencies support a position that a common set of variables
      control alcohol self-administration across these populations.

PMID- 11224379
TI  - Diurnal patterns of cocaine and heroin self-administration in rhesus monkeys
      responding under a schedule of multiple daily sessions.
AB  - A number of non-pharmacological factors have been shown to influence drug self
      administration in experimental animals. This report examines diurnal changes in
      drug self-administration by rhesus monkeys trained to self-administer food (1gm
      fruit-flavored pellets) and cocaine (0.01 or 0.032mg/kg/injection) under a second
      order FR4 (VR16:S) schedule during four daily food and drug self-administration
      sessions. Saline, different unit doses of cocaine (0.001-0.1mg/kg/injection) or
      different unit doses of heroin (0.0001-0.01mg/kg/injection) were substituted for
      the maintenance dose of cocaine during drug sessions. Dose-effect curves relating
      unit dose of cocaine or heroin to the number of injections per session displayed
      an inverted U-shape during each of the four daily drug sessions. When
      0.032mg/kg/injection cocaine or 0.0032mg/kg/injection heroin were available,
      monkeys usually self-administered the maximum number of injections during all
      four drug sessions. Substitution of saline or lower unit doses of cocaine (0.001
      0.01mg/kg/injection) or heroin (0.0001-0.001mg/kg/injection) decreased the number
      of injections/session; however, these decreases were consistently greater during
      the evening (20.00-21.00h) and morning (07.00-08.00h) sessions than during the
      afternoon sessions (12.00-13.00h and 16.00-17.00h). As a result, the ascending
      limbs of the cocaine and heroin dose-effect curves for the evening and morning
      sessions were shifted to the right of the ascending limbs of the dose-effect
      curves for the afternoon sessions. Moreover, when saline was substituted for
      cocaine for only two sessions per day, drug self-administration decreased more
      during the evening and morning sessions even when the cocaine was available
      during those sessions. These findings suggest a diurnal variation in cocaine and
      heroin self-administration. Specifically, drug self-administration during the
      evening and morning sessions appears to be more sensitive to a decrease in
      reinforcer magnitude than responding during the afternoon sessions. These
      findings confirm and extend previous reports of the influence of non
      pharmacological factors on drug self-administration.

PMID- 11224380
TI  - Tolerance and cross-tolerance to the response rate-decreasing effects of u
      opioids in morphine-maintained squirrel monkeys.
AB  - The purpose of the present experiment was to assess the degree of tolerance and
      cross-tolerance to the response rate-decreasing effects of opioids with different
      degrees of intrinsic efficacy at the mu receptor. The mu opioids included
      buprenorphine, etorphine, l-methadone, morphine, and sufentanil. Lever pressing
      of squirrel monkeys was maintained by a fixed-ratio (FR) 30 schedule of food
      presentation, and dose-effect curves for each drug were obtained prior to,
      during, and after daily administrations of morphine. Each of the mu opioids, and
      the non-opioid pentobarbital, dose-dependently decreased response rates. Daily
      administration of morphine produced approximately a 0.9 log unit rightward shift
      in the morphine dose-effect curve. During this chronic-morphine phase of the
      experiment, the dose-effect curve for pentobarbital was not shifted consistently,
      whereas the dose-effect curves for buprenorphine, etorphine, l-methadone, and
      sufentanil were shifted between 0.4 and 0.6 log unit to the right. Therefore
      etorphine, l-methadone and sufentanil, mu opioids thought to have high intrinsic
      efficacy, and buprenorphine, a mu opioid thought to have low intrinsic efficacy,
      all produced a smaller degree of cross-tolerance than that observed for morphine,
      and pentobarbital, a non-opioid, did not produce cross-tolerance.

PMID- 11224381
TI  - Dopamine D1-like receptor agonists impair responding for conditioned reward in
      rats.
AB  - The dopamine (DA) D1-like receptor agonist SKF 38393 has been reported to impair
      responding for conditioned reward. SKF 38393 is a partial agonist and it is
      possible that the impairment occurred because it prevented endogenous DA from
      having its full impact on the D1-like receptor. The present experiments evaluated
      this possibility by examining the effects of several D1-like agonists with
      differing efficacy at stimulating adenylate cyclase. Male rats (n = 203) were
      trained in a procedure with three distinct phases. During the pre-exposure phase
      the rats were exposed for five 40min sessions to an operant chamber containing
      two levers; one produced a lights-off and the other a tone stimulus (3s). This
      was followed by the conditioning phase, four sessions during which the levers
      were removed and the rats received pairings of the lights-off stimulus (80 per
      day) with food, presented according to a variable time 45s schedule. The test
      phase included two sessions during which the levers were present and the number
      of responses made on each lever was calculated as a ratio of the number of
      responses made during pre-exposure. Drugs were administered prior to each test
      session. No-injection and saline groups showed a higher ratio of responding for
      the lights-off than the tone stimulus, indicating that the lights-off stimulus
      had become a conditioned reward. The full D1-like agonist SKF 82958 (0.01
      1.0mg/kg, s.c.) and the partial agonists SKF 81297 (0.01-1.0mg/kg), SKF 77434
      (0.01-5.0mg/kg) and CY 208-243 (0.01-1.0mg/kg) impaired responding for
      conditioned reward at one or more of the highest doses. Results suggest that the
      impairments previously seen with SKF 38393 are not attributable to the partial
      agonist action of that drug, and continue to support the hypothesis that
      responding for conditioned reward is dependent on a reward-related DA signal at
      the D1-like receptor.

PMID- 11224382
TI  - Genetic differences in the operant rate-depressant effects of ethanol between
      four inbred mouse strains.
AB  - The use of genetically defined populations in studies of ethanol on schedule
      controlled behavior can help determine genetically underlying responses to
      ethanol as well as the role of environmental constraints in the expression of
      gene effects. The purpose of the present study was to investigate the rate
      depressant effects of ethanol in four inbred mouse strains, A/J, CBA/J, C3H/HeJ
      and DBA/2J. Ethanol dose-dependently decreased high rates of behavior maintained
      by fixed-ratio responding for study in all four strains. In general, DBA/2J mice
      were the least sensitive to the rate-depressant effects of ethanol, with an A/J
      averaging 19.29% greater than the other three inbred strains. The results of this
      experiment demonstrate that genetic factors play a role in determining
      responsitivity to even a complex learned behavioral sequence such as lever press
      responding with a fixed ratio schedule, and that sensitivity to the effects of
      ethanol on fixed-ratio responding for water is not genetically related to acute
      narcotic effects or reinforcing effects of ethanol.

PMID- 11224383
TI  - A comparison of the effects of amphetamine, strychnine and caffeine on prepulse
      inhibition and latent inhibition.
AB  - Sensorimotor gating deficits characterize several neuropsychiatric disorders,
      including schizophrenia. Prepulse inhibition (PPI) and latent inhibition (LI) are
      measures that are used to assess sensorimotor gating and have been found to be
      reduced in schizophrenia patients. In PPI, a weak stimulus presented immediately
      prior to a startling stimulus attenuates the startle response. In LI, pre
      exposure to a stimulus retards the subsequent association of that stimulus with a
      consequence (e.g. footshock). In rats, indirect dopamine (DA) agonists such as
      amphetamine disrupt both PPI and LI. Amphetamine has also been reported to
      increase exploratory locomotion at doses that decrease PPI and LI. Such
      behavioral activation might complicate the interpretation of amphetamine-induced
      changes in measures of sensorimotor gating. The present study was conducted in
      order to compare the effects of three behaviorally activating drugs on PPI, LI
      and locomotor activity. Separate groups of rats were treated with either vehicle,
      the DA releaser amphetamine (1.5mg/kg), the glycine antagonist strychnine
      (0.75mg/kg), or the adenosine receptor antagonist caffeine (10mg/kg) and then
      tested in either startle chambers (for PPI) or an active avoidance chamber (for
      LI). Locomotion was measured by inter-trial crossing in the avoidance chamber.
      Amphetamine stimulated locomotion and disrupted both PPI and LI, but did not
      elevate startle amplitude. In contrast, caffeine increased locomotion, but had no
      effect on PPI or LI. Strychnine did not increase locomotion significantly, but
      did increase startle amplitude and disrupt PPI and LI. Hence, neither increased
      startle amplitude nor locomotor activation are necessary or sufficient conditions
      for disruption of sensorimotor gating as measured by PPI and LI.

PMID- 11224384
TI  - Impulsivity predicts individual susceptibility to high levels of alcohol self
      administration.
AB  - Clinical studies indicate large individual differences in susceptibility to
      alcohol abuse. Poor behavioral self -regulation has been proposed to reflect a
      predisposing factor. Like humans, only some rats regularly consume large and
      intoxicating amounts of alcohol. We hypothesized that clinical indications of
      impaired behavioral self-regulation should be reflected in an animal model of
      impulse control, and in this study we assessed impulsivity with a delay-of-reward
      paradigm. We found that three groups representing three levels of impulsivity
      predicted augmenting levels of alcohol self-administration. Also, overall
      impulsivity scores were found to be significantly correlated with magnitude of
      alcohol self-administration. The finding that high impulsivity is linked to
      elevated consumption represents an animal model that may mirror clinical
      depictions of an alcohol abuse syndrome. This animal model may help elucidate the
      neurobiological basis of individual susceptibility to alcohol addiction.

PMID- 11224385
TI  - Nor-binaltorphimine: an ultra-long acting kappa-opioid antagonist in pigeons.
AB  - This study assessed the ability of naltrexone and nor-binaltorphimine (NBNI) to
      antagonize the rate-decreasing effects of opioid agonists. Food-restricted
      pigeons were trained to peck a lit key under a fixed-ratio (FR) 20 schedule of
      food reinforcement. Bremazocine, a kappa-opioid agonist, decreased food
      reinforced responding (ED(50) = 0.02mg/kg), and naltrexone (5.6mg/kg) reduced the
      potency of bremazocine six-fold. The effect of naltrexone lasted less than 24h. A
      single injection of NBNI (1mg/kg) was given to four pigeons, and the time course
      of antagonism of the rate-decreasing effects of bremazocine was measured. One
      hour after NBNI was given, it was ineffective. Eight days later, NBNI produced a
      five-fold reduction in the potency of bremazocine. Between 12 and 20 days after
      NBNI, it reduced the potency of bremazocine 14-fold. NBNI continued to antagonize
      bremazocine for 11 weeks. Smaller doses of NBNI (0.001-0.1mg/kg) were
      ineffective. The effect of NBNI was not due to tolerance to bremazocine, since
      tolerance failed to develop to bremazocine administered repeatedly. NBNI (1mg/kg)
      did not antagonize the response rate-decreasing effects of morphine, a mu-opioid
      agonist, or BW373U86, a delta-opioid agonist. NBNI was an effective and extremely
      long-lasting kappa-opioid antagonist in the pigeon. The duration of action of
      NBNI is among the longest yet described in any species.

PMID- 11224386
TI  - Evaluation of the effects of cocaine, heroin and naltrexone, alone and in
      combination, on milk drinking in rats.
AB  - The effects of cocaine, alone and in combination with either heroin or
      naltrexone, were examined using a milk drinking procedure in rats. Rats (n=8)
      were given access to a sweetened milk solution for 15min daily until intake had
      stabilized (3 days with less than 10% variation across days). Rats were first
      administered saline or one of five doses of either cocaine (2.0-32mg/kg, i.p.) or
      heroin (0.4-3.2mg/kg, i.p.) 15min prior to milk access. The dose-response
      function for cocaine was then determined in combination with either 0.8mg/kg or
      1.6mg/kg heroin. Both cocaine and heroin administered alone produced dose
      dependent decreases in milk drinking. Combination with 0.8mg/kg and 1.6mg/kg
      heroin resulted in parallel shifts to the left in the cocaine dose-response
      function. Isobolographic analysis of these dose-response functions using ED(50)
      and ED(75) values revealed that the combinations of cocaine and heroin were dose
      additive, except at the cocaine plus 1.6mg/kg heroin combination, which was infra
      additive. Redetermination of the cocaine-only and heroin-only dose-response
      functions revealed no significant difference from the first determination. To
      assess the effects of naltrexone on cocaine- and heroin-induced suppression of
      milk drinking, rats were first administered four doses of naltrexone (0.1
      0.8mg/kg, i.p., 15min pretreatment). Then, naltrexone doses were combined with a
      dose of heroin or cocaine that suppressed milk drinking (3.2 and 16mg/kg,
      respectively). Naltrexone alone produced modest, but not dose-related,
      suppression of milk drinking, and had no reliable effect on suppression of milk
      drinking produced by 16mg/kg cocaine. In contrast, naltrexone dose-dependently
      blocked heroin-induced suppression of milk drinking and, at naltrexone doses that
      had no effect on milk drinking when administered alone, produced a parallel shift
      to the right in the heroin dose-response function. In vivo apparent pK(B)
      analyses revealed that naltrexone antagonism of heroin-induced suppression of
      milk drinking involved u-opioid receptors. Taken together, these results suggest
      that the effects of cocaine and heroin on milk drinking are either dose-additive
      or infra-additive and that cocaine-induced suppression of milk drinking does not
      directly involve the u-opioid receptor system.

PMID- 11224387
TI  - New dibenzazepine derivatives with disinhibitory and/or antidepressant potential:
      neurochemical and behavioural study in the open-field and forced swimming tests.
AB  - Original bioisosteric analogues of clozapine were evaluated for potential
      disinhibitory and/or antidepressant effects using the open-field test in the rat
      and Porsolt's forced swimming test in the mouse. Attempts to relate the
      behavioural results to the binding affinities for dopamine (D1, D2), serotonin (5
      HT(2)) and muscarinic (M) receptors were also undertaken. In the open-field test,
      two main profiles were observed. The first profile corresponded to disinhibitory
      molecules resembling diazepam and ritanserin. The second profile corresponded to
      antipsychotic compounds resembling either typical (haloperidol, clothiapine) or
      atypical (clozapine) neuroleptics. The results obtained in the forced swimming
      test confirmed the neuroleptic-like activity of the second group of compounds,
      while two compounds of the first group (JL 3 and JL 26) showed an antidepressant
      like activity, JL 3 being as active as imipramine. While it was not possible to
      relate the first profile to any binding interaction, a relation could be
      established among the second group of compounds between the typical or atypical
      antipsychotic behavioural profile and the 5-HT(2)/D2 ratio.

PMID- 11224388
TI  - DOI disruption of prepulse inhibition of startle in the rat is mediated by 5
      HT(2A) and not by 5-HT(2C) receptors.
AB  - Prepulse inhibition (PPI) of the startle response is used as a measure of
      sensorimotor inhibitory processes. Deficits in PPI have been found in patients
      with schizophrenia, obsessive compulsive disorder (OCD) and Huntington's disease.
      PPI can also be disrupted in animals through manipulations that augment
      serotonergic activity, such as administration of the serotonin (5-HT) agonists 8
      OH-DPAT, RU 24969 and DOI. In the present experiment the identity of the 5-HT
      receptor subtype that mediates the DOI-induced disruption of PPI was examined.
      Dose-response studies revealed that the novel 5-HT(2A) antagonist, MDL 100,907
      (0.01, 0.1 and 1.0mg/kg, s.c.), but not the new 5-HT(2C) antagonist SDZ SER 082
      (0.125, 0.25 and 0.5mg/kg, s.c.), prevented the loss of PPI induced by DOI (0.25
      or 0.5mg/kg, s.c.). The results support the hypothesis that the 5-HT(2A) receptor
      is involved in the modulation of sensorimotor gating. Because deficits in PPI are
      used as a model of sensorimotor gating abnormalities found in schizophrenia, the
      present study supports the view that MDL 100,907 may be a novel atypical
      antipsychotic. Studies of the serotonergic substrates of PPI may provide a model
      of the possible serotonergic role in the sensorimotor gating abnormalities in
      schizophrenia and OCD patients.

PMID- 11224389
TI  - The effects of dopamine agonists on rotational behavior in non-tolerant and
      caffeine-tolerant rats.
AB  - Tolerance develops to caffeine-induced stimulation of both locomotor activity and
      rotational behavior. The role of dopamine in tolerance to the locomotor stimulant
      effects of caffeine has been documented. However, the role of dopamine in
      caffeine-induced turning behavior remains to be elucidated. Therefore, the
      present study determined the role of dopamine receptors in tolerance to caffeine
      induced rotational behavior. Rats with a unilateral lesion of the nigrostriatal
      tract, induced by 6-hydroxydopamine (6-OHDA), were treated chronically with
      either caffeine (1.0mg/ml) or with drug-free tap water, by a method of scheduled
      access. Agonists with and without selectivity for dopamine receptor sub-types
      were tested in both groups of rats (nonselective: apomorphine, d-amphetamine; D1
      selective: SKF-38393, SKF-77434; D2 selective: R(-)-propylnorapomorphine (NPA),
      quinpirole). All drugs produced dose-dependent increases in turning that, with
      the exception of quinpirole, were comparable in both groups. Quinpirole produced
      a smaller effect in rats treated with caffeine than in control rats. Thus, there
      was significant cross-tolerance only to the effects of quinpirole. The concurrent
      administration of SKF-38393 with NPA produced a synergistic interaction on
      rotational behavior in control rats, to which cross-tolerance did not develop in
      caffeine-treated rats. In contrast to what occurs with locomotor activity, in
      control rats the selective D1 dopamine receptor antagonist SCH 23390 completely
      blocked SKF-38393-induced turning behavior and the selective D2 dopamine receptor
      antagonist eticlopride partially attenuated this effect. NPA-induced turning
      behavior was blocked only by eticlopride; SCH 23390 was without effect. Both SCH
      23390 and eticlopride blocked d-amphetamine-induced rotational behavior. The
      results of this study suggest that D1 dopamine receptors are not involved in
      tolerance to caffeine-induced rotational behavior. The role of D2 dopamine
      receptors in this effect is unresolved. Results obtained from rotational behavior
      studies generally do not parallel those obtained from locomotor activity studies,
      suggesting that different mechanisms underlie the effects of caffeine on these
      two behaviors.

PMID- 11224390
TI  - Phencyclidine-induced stereotyped behaviour and social isolation in rats: a
      possible animal model of schizophrenia.
AB  - Phencyclidine (PCP) can induce a model psychosis in humans that mimics the
      positive and negative symptoms of schizophrenia. The purpose of the present study
      was to determine whether PCP can induce similar behavioural effects in rats and
      whether these effects can be alleviated by neuroleptic drug treatment. Rats were
      tested in the social interaction test, and their behaviour was quantified by an
      automated video-tracking system and manual scorings of stereotyped behaviour and
      ataxia. The behavioural effects of different dose- and administration regimes of
      PCP were initially determined, and it was found that PCP dose-dependently induced
      stereotyped behaviour and social isolation in the rats. Comparison to clinical
      studies suggests that these behaviours correspond to certain aspects of the
      positive and negative symptoms, respectively, of a PCP psychosis in humans.
      Subsequently, the effects of 3 or 21 days of administration of the antipsychotic
      drugs haloperidol or clozapine on the behaviour of either vehicle- or PCP-treated
      rats were determined. Haloperidol did not produce a selective antagonism of PCP,
      whereas chronic clozapine selectively inhibited the PCP-induced stereotyped
      behaviour and social isolation. These effects of haloperidol and clozapine
      suggest that this animal model can determine the effects of neuroleptic drugs on
      positive and negative symptoms, onset of action, and side-effect profile,
      including effects on the motor system. Together these data suggest that this may
      be a possible animal model of the positive and negative symptoms of
      schizophrenia.

PMID- 11224391
TI  - Pavlovian conditioning of psychomotor stimulant-induced behaviours: has
      convenience led us astray?
AB  - In order to classically condition the behavioural effects of psychomotor
      stimulants within a test context, rats were treated for 10 days with (+)
      amphetamine (1.5mg/kg), (+)-4-propyl-9-hydroxynaphthoxazine (PHNO, 30ug/kg) or
      vehicle prior to a 1h placement into a test box. Conditioned behavioural effects
      were then measured in the previously drug-paired context after a vehicle
      injection (drug-free test day). Each rat was videotaped for the 1h test box
      exposure on days 1, 4, 7 and 10 of the drug conditioning trials, and on the drug
      free test day. Eleven of 28 behaviours that were scored for frequency, duration
      and mean bout duration (bout length) were significantly influenced by at least
      one of the two drugs. Amphetamine predominantly increased bout lengths while PHNO
      predominantly increased bout frequency. Only two measures that were influenced by
      the drugs exhibited clear increases over controls in a manner consistent with a
      classical conditioning interpretation. Behavioural sensitization clearly occurred
      to some of the effects of amphetamine and PHNO, but these were not the same
      effects as those increased on the non-drug day testing for classical
      conditioning. Most behavioural effects of amphetamine and PHNO are not
      classically conditioned, and behavioural sensitization to these drugs, while
      perhaps context-specific, is not due to classical conditioning. Automated
      measures of behaviours have provided misleading evidence concerning the
      similarity among behavioural effects of stimulants, sensitization and effects of
      exposure to an environment previously paired with stimulants. Analysis of
      transitions between behaviours does not support the view that stimulants increase
      switching or response competition, or that behavioural reorganization is
      responsible for sensitization. Rather, it is suggested that stimulants
      selectively facilitate current stimulus-guided behaviours.

PMID- 11224392
TI  - Effects of clozapine on latent inhibition in the rat.
AB  - In the present study we have examined the effect of clozapine, an atypical
      antipsychotic drug, on latent inhibition (LI) using the conditioned emotional
      response (CER) procedure. In this procedure, ten pre-exposures to the to-be
      conditioned stimulus result in weak or no LI whereas 30 pre-exposures produce
      robust LI. Three different experimental protocols were used to study the effects
      of clozapine: facilitation of LI in animals subjected to ten pre-exposures to the
      to-be-conditioned stimulus; antagonism of the disruptive effect of amphetamine
      (1mg/kg, s.c.) on LI in animals receiving 30 pre-exposures; antagonism of the
      disruptive effect of nicotine (0.6mg/kg, s.c.) on LI in animals receiving 30 pre
      exposures. High doses of clozapine (3 and 10mg/kg, s.c.) disrupted the CER in non
      pre-exposed animals. Despite this, clozapine significantly facilitated the
      development of LI at 1 and 10mg/kg and significantly attenuated the disruptive
      effects of nicotine at 0.3 and 1mg/kg and of amphetamine at 2 and 5mg/kg. These
      results demonstrate that clozapine is active in the LI model and further support
      the utility of this model in the study of mechanisms of action of antipsychotic
      drugs.

PMID- 11224393
TI  - Behavioural specificity of chlordiazepoxide-produced StD.
AB  - Low doses of benzodiazepines produce state-dependence (StD) of food-rewarded
      lever pressing in rats, and it has been hypothesized that the changes of memory
      states that can thus be studied constitute the mechanism whereby benzodiazepines
      cause their characteristic psychopharmacological actions such as anxiolysis,
      apparent memory loss and dependence. Non-benzodiazepine CNS agents such as NMDA
      antagonists also produce StD in this procedure, suggesting that the StD
      hypothesis of psychopharmacological drug action can be expanded to include agents
      other than benzodiazepines. For this expansion to be possible, however, it must
      be shown that the StD mechanism operates in a specific manner. The present
      experiments examined whether varying the extent of food deprivation affects any
      of a number of quantitative features of chlordiazepoxide (CDP)-induced StD of
      food-rewarded lever pressing in rats. The data indicate that the CDP doses
      required to generate StD in both drug-to-saline and dose-to-dose transfer tests,
      are considerably lower in relatively sated as opposed to more deprived animals;
      little or no difference was found in tests assaying saline-to-drug transfer. The
      data add behavioural to available pharmacological evidence supporting the
      hypothesis that changes of memory state constitute the mechanism whereby CNS
      agents such as benzodiazepines and NMDA antagonists cause their characteristic
      psychopharmacological actions. Some directions for future research are identified
      to explore further the pharmacological and behavioural specificity of drug
      produced StD.

PMID- 11224394
TI  - Effects of metrifonate on escape and avoidance learning in young and aged rats.
AB  - The present study assessed the effects of the indirect acetylcholinesterase
      inhibitor metrifonate on learning and memory functions in young (3-month-old) and
      aged (25-month-old) rats. In the shuttle box, metrifonate at a dose of 12.5mg/kg,
      p.o., 30min before each of the daily acquisition sessions, improved the
      acquisition of the active avoidance response, whereas a dose of 25mg/kg did not.
      Metrifonate, 12.5mg/kg, p.o., administered before each of the daily acquisition
      sessions, also facilitated the acquisition of the Morris water escape task in
      both young and aged rats: metrifonate-treated rats swam a shorter distance to
      reach the escape platform than did the vehicle-treated rats. The 3-month-old rats
      treated with metrifonate did not show the increase in swimming speed over
      training observed in vehicle-treated animals; no effects of metrifonate were
      found on the swimming speed of aged rats. In a probe trial carried out
      immediately after the fifth daily acquisition session, metrifonate treatment did
      not affect the bias of the aged rats for the quadrant in which the platform had
      been positioned during acquisition. It is concluded that metrifonate improves
      performance during the acquisition phase of two aversively motivated learning and
      memory tasks at the dose of 12.5mg/kg, p.o.

PMID- 11224395
TI  - Central mediation of the cannabinoid cue: activity of a selective CB1 antagonist,
      SR 141716A.
AB  - Active cannabimimetic drugs are known to bind to two receptor subtypes: one,
      called CB1, is mainly localised in the central nervous system while the other
      (CB2) is expressed preferentially in the immune system. SR 141716A has been
      demonstrated to have a nanomolar affinity for CB1 receptor subtypes and a
      micromolar affinity for CB2 receptors. Moreover, it is an effective antagonist at
      these receptors both in vitro (antagonism of cannabinoid activity in vas
      deferens) and in vivo (suppression of the hypothermia elicited by WIN 55,212-2).
      The present experiments were thus undertaken to investigate the role of CB1
      receptors in cannabinoid discrimination. Rats were trained to discriminate WIN
      55,212-2 (0.3mg/kg s.c.) from saline in a standard operant (FR10) food rewarded
      discrimination procedure. Acquisition of the discrimination required 16 days on
      average and the ED(50) of WIN 55,212-2 was 0.032mg/kg s.c. CP55,940 and delta-9
      tetrahydrocannabinol (Delta(9)-THC) generalised to the WIN 55,212-2 stimulus with
      the respective ED(50)s of 0.007mg/kg (s.c.) and 0.64mg/kg (p.o.). Pretreatment
      with SR 141716A antagonised the cue elicited by WIN 55,212-2 (ED(50) = 1.6mg/kg)
      as well as the generalisation to CP 55,940 (ED(50) = 0.08mg/kg) and to Delta(9)
      THC (ED(50) = 0.15mg/kg). SR 140098 is a CB1 antagonist as potent as SR 141716A
      in vitro. This compound is unlikely to pass into the brain since it failed to
      displace [(3)H]-CP55, 940 from rat brain membranes ex vivo, and to reverse WIN
      55,212-2-induced hypothermia. SR 140098, in contrast to SR 141716A, did not
      antagonise the WIN 55,212-2 stimulus. Taken together, the present results
      demonstrate that the brain CB1 receptor subtype mediates the cannabinoid cue.

PMID- 11224396
TI  - Discriminative stimulus effects of the benzodiazepine receptor partial agonist
      bretazenil in pigeons and in rats.
AB  - Bretazenil is a partial agonist at diazepam-sensitive (DS) GABA(A) receptors, and
      it also binds with high affinity to diazepaminsensitive (DI) GABA(A) receptors. A
      unique discriminative stimulus effect transduced by binding at DI benzodiazepine
      (BZ) receptors has been reported in pigeons, but has not been established in
      rats. Further, differences have been observed between rats and pigeons in results
      of drug discrimination experiments utilizing BZ receptor partial agonists.
      Therefore, to examine the discriminative stimulus effects of bretazenil and to
      explore the possibility of species differences in substitution profiles, pigeons
      and rats were trained to discriminate 0.3mg/kg bretazenil from vehicle.
      Flumazenil (0.03-1.0mg/kg) did not substitute for bretazenil in pigeons, despite
      full substitution of bretazenil for flumazenil in this species. Flumazenil (0.03
      10.0mg/kg) also did not substitute for bretazenil in rats, despite the partial
      agonist effects of flumazenil in rats. Likewise, midazolam (0.3-1.0mg/kg) did not
      substitute for bretazenil in pigeons, despite the fact that bretazenil partially
      substitutes for midazolam in pigeons. However in rats, midazolam produced full,
      dose-dependent substitution (0.03-3.2mg/kg). Differences may result from
      different fractional receptor occupancy requirements for the mediation of
      discriminative stimulus effects through DS BZ receptors, and/or from a
      contribution of DI BZ receptor binding in pigeons.

PMID- 11224397
TI  - Gustatory preference-aversion profiles for saccharin, quinine and alcohol in
      Roman high- and low-avoidance lines.
AB  - Rats of the Roman high-(RHA) and low-avoidance (RLA) lines are known to differ in
      alcohol preference, since the RHA rats freely consume more ethanol than RLA
      animals. In order to investigate whether this difference in alcohol intake could
      be due to an alteration of the gustatory quality of ethanol induced by the
      selection, we compared taste preference and aversion responses of RHA and RLA
      rats in four procedures: saccharin-water choice; gustatory negative contrast;
      quinine-water choice and 10% v/v alcohol-water choice. Our results confirm that
      RHA rats drink more alcohol than RLA rats. In the saccharin-water choice task,
      RHA rats tended to show higher preference than RLA rats for the most palatable
      concentrations, while their aversion to the highest concentration of saccharin
      (50mM) was smaller than the aversion shown by RLA rats. The negative gustatory
      contrast test did not clearly differentiate the two lines, although only RHA rats
      showed significant negative contrast. Lastly, while RLA rats showed only aversion
      to quinine as the concentration increased, RHA rats did not show any aversion and
      preferred quinine to water at mid-range concentrations. To explain these results
      three hypotheses are briefly discussed: first, selective breeding for high
      avoidance learning could have enhanced brain reinforcement processes implicated
      in the evaluation of palatability. Secondly, selective breeding could have
      decreased aversiveness to quinine-adulterated solutions, as well as to saccharin
      and alcohol solutions which include a quinine-like taste component. Lastly, the
      present results suggest that the RHA rats may be high sensation-seekers whereas
      RLA animals are low sensation-seekers.

PMID- 11224398
TI  - Evidence that GABA(A) but not GABA(B) receptor activation in the dorsal raphe
      nucleus modulates ethanol intake in Wistar rats.
AB  - Injection of the GABA(A) agonist muscimol into the dorsal raphe nucleus produces
      a marked and selective increase in voluntary ethanol intake. The purpose of the
      present study was threefold: first, to demonstrate that the effect of muscimol on
      ethanol consumption is mediated by GABA(A) receptors; secondly, to test the
      generalizability of this effect by examining the effects of another GABA(A)
      agonist, THIP, on ethanol drinking; and finally, to examine whether GABA(B)
      receptors within the dorsal raphe also play a role in modifying voluntary ethanol
      consumption under the same experimental conditions. Rats were trained to drink a
      12% ethanol solution in a limited access paradigm with water concurrently
      available. Muscimol (50ng) injected into the dorsal raphe enhanced intake by at
      least 100%. Peripheral administration of the GABA(A) antagonist bicuculline
      (4mg/kg), but not the 5-HT(1A) antagonist (+)- WAY100135 (1 and 3mg/kg),
      antagonized the stimulatory effect of muscimol at a dose which, when administered
      alone, did not alter ethanol intake. This supports the suggestion that the effect
      of muscimol is mediated via GABA(A) receptors. This conclusion was further
      supported by the finding that another GABA(A) agonist, THIP (500ng), also
      selectively increased ethanol intake in this paradigm. Injection of bicuculline
      (60ng) into the dorsal raphe reduced ethanol intake, but also appeared to reduce
      water intake. Finally, intra-dorsal raphe injection of the GABA(B) agonist
      baclofen (62.5 and 125ng) did not produce any change in ethanol or water
      consumption. Together, these findings suggest that enhancement of GABAergic
      activity in the dorsal raphe increased voluntary ethanol intake via activation of
      GABA(A) but not GABA(B) receptors.

PMID- 11224399
TI  - Quinpirole-induced locomotor stimulation in rats develops rapid sensitization
      when combined with brief footshocks.
AB  - In rats exploring a symmetrical Y-maze, an acute injection of quinpirole or
      intermittent brief footshocks did not change the level of locomotion. The
      combined treatment of quinpirole and footshocks elicited an immediate locomotor
      stimulation. When the experimental session was repeated daily, there was a
      further increase of hyperlocomotion (i.e. sensitization). In parallel groups of
      rats treated with quinpirole and placed in the Y-maze daily without shock, or
      subjected only to daily footshock, locomotor activity did not increase.
      Footshock, therefore, has a synergistic effect in the development of
      sensitization to quinpirole. When the dose-response relationships of quinpirole
      were compared between naive and sensitized animals, the magnitude of stimulation
      differed, but the threshold stimulant dose did not change. Pretreatment with
      sulpiride completely antagonized the hyperlocomotion in both drug-naive and
      quinpirole-sensitized rats. The results support a view that quinpirole
      facilitates the emergence of patterned motor behaviors. Non-contingent, brief
      footshock elicits running as the prepotent behavior in the Y-maze, and hastens
      the development of behavioral sensitization to quinpirole.

PMID- 11224400
TI  - In vivo measurement of extracellular serotonin in the ventral hippocampus during
      treadmill running.
AB  - The present study used the microdialysis technique to investigate the effect of
      treadmill running, without the use of an electric grid, on extracellular
      serotonin in the ventral hippocampus of male Lister hooded rat. Extracellular
      hippocampal serotonin was measured during 60min of treadmill running at 20m/min
      and compared with control animals who were placed on the stationary treadmill for
      60min. The exercised animals had been habituated to the treadmill and trained for
      4-5 weeks so as to be able to run for 60min, while the control animals had been
      placed on the stationary treadmill as frequently and for the same length of time
      as the exercising group. Extracellular hippocampal serotonin was higher (p <
      0.05) during the first 40min of exercise than after 40min of being placed on the
      stationary treadmill, but this increase occurred only in those animals that
      learned more slowly and ran a shorter distance (1030+/-30m) and not in those that
      learned more rapidly and ran further (1150+/-20m).

PMID- 11224401
TI  - Effects of dopaminergic D3-receptor-preferring ligands on the acquisition of
      place conditioning in rats.
AB  - The involvement of a D3 receptor-mediated control of dopamine (DA) function in
      motivational processes was investigated in rats by examining the ability of two
      D3 receptor-preferring ligands (7-OH-DPAT and l-nafadotride) to establish
      incentive learning and/or to modulate the reinforcing properties of food. This
      was done using a place conditioning procedure which consisted of repeated
      pairings of a drug (or food + drug) with a single environmental cue, the floor
      texture of an open field. (+/-)7-OH-DPAT, a partially selective D3 receptor
      agonist, produced a biphasic effect: the time spent on the drug-paired texture
      was reduced by 4 and 8ug/kg and lengthened by 4.0mg/kg, suggesting intrinsic
      aversive and appetitive potentials, depending on the dose. The D3 receptor
      preferring antagonist, l-nafadotride, did not establish place conditioning and
      seemed therefore devoid of intrinsic reinforcing properties. However, when food
      was provided during the conditioning sessions preceded by drug administration, a
      low dose of l-nafadotride (0.12mg/kg) but not higher doses, lengthened the time
      spent on the food-paired texture. Although the preferential affinity ratio of the
      two ligands in favour of the D3 vs. D2 subtype is low, these results suggest that
      DA function in the structures involved in incentive learning could be controlled
      through inhibitory D3 (or 'D2-like') receptor-mediated processes. Conditioned
      place aversion would indicate an impaired DA transmission due to a selective
      stimulation of these receptors, whereas their selective blockade would induce the
      inverse effect, providing that DA release was sufficient (as during eating) in
      the pathways involved in reward-related processes. The reversal of the effects of
      the two compounds at larger doses would likely result from an interaction with
      other subtypes of 'D2-like' receptors.

PMID- 11224402
TI  - Effects of H(1)-antagonists on discriminative stimulus effects of cocaine and
      methamphetamine in rats.
AB  - The effects of H(1)-antagonists, such as tripelennamine, chlorpheniramine and
      pyrilamine, on the discriminative stimulus effects of cocaine and methamphetamine
      in rats were examined. Rats were trained to discriminate between cocaine
      (10mg/kg, i.p.) or methamphetamine (1.0mg/kg, i.p.) and saline, with responses
      maintained under a fixed-ratio 10 (FR10) schedule of food delivery. In
      generalization tests, tripelennamine generalized to the discriminative stimulus
      effects of cocaine and methamphetamine, while chlorpheniramine only generalized
      to cocaine. These generalizations of tripelennamine and chlorpheniramine were
      attenuated by the dopamine receptor antagonist haloperidol. Furthermore,
      tripelennamine and chlorpheniramine, but not pyrilamine, potentiated the
      discriminative stimulus effects of cocaine and methamphetamine. These results
      suggest that some H(1)-antagonists possess cocaine- and/or methamphetamine-like
      discriminative stimulus effects which may be mediated by the dopaminergic system,
      and as a result the discriminative stimulus effects of cocaine and
      methamphetamine were potentiated by these H(1)-antagonists.

PMID- 11224403
TI  - Calcium dependence of sensitised dopamine release in rat nucleus accumbens
      following amphetamine challenge: implications for the disruption of latent
      inhibition.
AB  - Repeated amphetamine treatment results in sensitisation both of its behavioural
      effects, and of its dopamine (DA)-releasing effects on which the former largely
      depend. Understanding the nature of the sensitised response may help to explain
      behaviours which emerge only with repeated treatment, such as particular
      stereotypies and effects on social behaviour in animals, and links between these
      effects and the emergence of dependence and psychotic symptoms in humans. We show
      here that a single pretreatment with amphetamine (1mg/kg) is sufficient to
      sensitise the locomotor response to amphetamine challenge (1mg/kg) 24h later. We
      have used in vivo microdialysis in the nucleus accumbens in unrestrained rats to
      demonstrate a corresponding potentiation in the DA response; the marked increase
      in accumbens dialysate DA following amphetamine (to 427% of basal) was
      significantly potentiated (to 675% of basal) by the pretreatment, without any
      alteration in the basal DA. There was also no change in the expected reduction in
      DA metabolites. Replacement of perfusate calcium by magnesium left the response
      to acute amphetamine challenge substantially unaffected, as expected from
      previous reports; however, the potentiation of the DA response by amphetamine
      pretreatment was prevented. Similarly the potentiated response was attenuated by
      administration of ondansetron, a 5HT-3 antagonist, (0.01mg/kg) before each
      amphetamine treatment. The ability of amphetamine to disrupt latent inhibition
      (L1), which is also disrupted in acute schizophrenia, has been suggested to
      provide a model of schizophrenia linking underlying cognitive deficits with the
      DA theory of the disorder. Since LI is disrupted by two systemic administrations
      of amphetamine 24h apart, but not by one, the present results are consistent with
      the concept that it is the calcium, and hence impulse, dependence of increased
      accumbal DA release, rather than its magnitude, which is critical for the
      disruption of LI.

PMID- 11224404
TI  - Human methadone self-administration: effects of dose and ratio requirement.
AB  - The effects of response requirement and small doses of methadone on human oral
      self-administration of methadone were examined. Three methadone maintenance
      patients stabilized at a dose of 80mg methadone per day were recruited as
      subjects. Completing a response requirement, fixed ratio (FR) of 32, 64 or 128
      responses (FR32, FR64, FR128) on one button dispensed 10ml of drug solution.
      Completing the equivalent response requirement on a second concurrently available
      response button dispensed 10ml of vehicle. The opportunity to respond was
      unavailable until the drug or vehicle had been consumed. Each 10ml of drug
      solution contained methadone doses of 0.027, 0.054 or 0.108mg/ml. The frequency
      of deliveries was limited so that subjects could not ingest more than 54mg of
      methadone; the difference between the 80mg daily methadone dose and the methadone
      consumed in session was administered 30min post-session. At FR64 and FR128 the
      frequency of deliveries decreased, at the 0.054 and 0.027mg/ml doses, relative to
      the frequency of deliveries at FR32. The amount of methadone consumed increased
      with increases in methadone dose and decreased with increases in FR size. These
      results demonstrate the reinforcing effects of small unit doses of methadone.
      This procedure provides a sensitive baseline for examining effects of other
      pharmacological interventions on methadone ingestion in humans.

PMID- 11224405
TI  - Effects of chlordiazepoxide, nicotine and d-amphetamine in the rat potentiated
      startle model of anxiety.
AB  - The effects of acute administration of chlordiazepoxide (2.5 and 5.0mg/kg, i.p.),
      nicotine (0.05, 0.1 and 0.4mg/kg, s.c.) and d- amphetamine (0.5 and 1.0mg/kg,
      i.p.) on rat potentiated startle were investigated. Chlordiazepoxide, 2.5 and
      5.0mg/kg, attenuated potentiation of startle, indicating an anxiolytic profile,
      although the effect of the higher dose was less marked and was accompanied by a
      reduction in overall startle response, probably reflecting drug-induced sedation.
      Nicotine at doses of 0.05 and 0.4mg/kg had no significant effects in this test.
      However, 0.1mg/kg nicotine eliminated potentiation of startle (in two separate
      experiments), an action comparable to that of 2.5mg/kg chlordiazepoxide. d
      Amphetamine at doses of 0.5 and 1.0mg/kg did not significantly influence
      potentiation of startle. The results suggest that nicotine has an anxiolytic
      profile in the potentiated startle paradigm which is not due to its
      psychostimulant properties.

PMID- 11224406
TI  - Alcohol and the reward value of cigarette smoking.
AB  - People who drink alcohol are more likely to smoke, and experiments have shown
      that alcohol can increase cigarette smoking. However, it is not clear why alcohol
      consumption should increase smoking. To address this issue the current experiment
      looked at the effects of alcohol on a range of behavioural and subjective
      measures intended to assess the reward value of smoking. These included a
      preference test carried out after subjects had smoked cigarettes of one colour
      after consuming alcohol, and cigarettes of another colour after consuming non
      alcoholic drinks. In the preference test, subjects were offered the choice of
      smoking the alcoholic or non-alcoholic drink-paired cigarette. It was
      hypothesised that if alcohol increased the reward value of smoking, subjects
      would choose to smoke the alcohol-paired cigarette. Consumption of alcohol
      increased the length of time people spent smoking, increased the number of puffs
      taken on each cigarette, and increased the amount of tobacco burnt. There were
      also strong subjective effects, with subjects looking forward more to smoking
      after alcohol and reporting greater smoking satisfaction after alcohol. However,
      subjects did not show a preference for the cigarettes they had smoked after
      alcohol.

PMID- 11224407
TI  - Effects of buprenorphine on behaviour maintained by heroin and alfentanil in
      rhesus monkeys.
AB  - The mechanism by which buprenorphine reduces opioid self-administration in humans
      and animals is generally thought to be through its opioid agonist effects.
      Buprenorphine, given acutely i.v. to three rhesus monkeys 30min prior to a
      session in which a range of doses of either alfentanil or heroin was available,
      produced dose-related decreases in the potency of both opioid agonists. The
      effects of buprenorphine were generally surmounted by increasing the
      dose/injection of alfentanil or heroin available for self-administration,
      indicating that buprenorphine was acting as an opioid antagonist in this
      situation. These data suggest that at least part of the effectiveness of
      buprenorphine in reducing opioid administration by human opioid users may be via
      its opioid antagonist properties.

PMID- 11224408
TI  - Tolerance to the discriminative stimulus and reinforcing effects of ketamine.
AB  - In order to examine whether tolerance develops to the discriminative stimulus and
      reinforcing effects of ketamine, rats were trained either to discriminate
      ketamine (10mg/kg) from saline or to self-administer ketamine
      (1.1mg/kg/injection), and then treated with chronic ketamine (32mg/kg),
      administered i.p. every 8 hours for 7 days. No shift in the dose-response curve
      for either paradigm was obtained following this chronic regimen. However,
      following a 2-week rest period in which animals had no exposure to ketamine, the
      dose-response curve was shifted two-fold to the left, indicating increased
      sensitivity to the drug. Reinstatement of training shifted the dose-response
      curve back to the right in both paradigms. These results suggest that tolerance
      to the discriminative stimulus and reinforcing effects of ketamine develops
      during training. Examination of the self-administration training data support
      this assumption, since inter-reinforcer time decreases, reflecting an increase in
      ketamine intake over training sessions.

PMID- 11224409
TI  - Procedural examination of behavioural sensitisation to morphine: lack of blockade
      by MK-801, occurrence of sensitised sniffing, and evidence for cross
      sensitisation between morphine and MK-801.
AB  - Rats were tested in an open field, a "sniffing box" and an eight-arm maze, to
      examine in detail the behavioural changes induced by morphine (10mg/kg, i.p.) and
      MK-801 (0.1mg/kg, i.p.), either alone or in combination, during a 10 day
      treatment and subsequent drug challenges. In addition to locomotion, a number of
      other behaviours such as sniffing, rearing and exploration were examined. After
      morphine challenge, sensitised locomotion and rearing were found in the open
      field, and sensitised sniffing and turning were observed in the sniffing box. In
      addition, in the sniffing box, saline challenge produced significant conditioned
      sniffing and turning, and after a challenge with MK-801, sensitised sniffing and
      turning were seen in the group pretreated with morphine, suggesting a cross
      sensitisation between morphine and MK-801 (but not vice versa). In the eight-arm
      maze, sensitised locomotion was found after morphine challenge. Morphine and MK
      801 changed the preference for particular angles run during trials in a
      characteristic manner. In none of the behavioural measures was MK-801 able to
      block the development (and expression) of sensitisation to morphine. In several
      cases, rather, MK-801 enhanced the acute morphine effects. Sensitisation of
      sniffing suggests that sensitisation has also developed within the nigrostriatal
      dopamine system and not only within the mesolimbic dopamine system, as is
      generally discussed in the context of the most commonly assessed behaviour,
      locomotion. This finding argues for the additional use of the sniffing box in
      sensitisation experiments.

PMID- 11224410
TI  - Dissociation of effects of chronic diazepam treatment and withdrawal on
      hippocampal dialysate 5-HT and mCPP-induced anxiety in rats.
AB  - Acute (10mg/kg, i.p.) and chronic (10mg/kg/day, i.p. for 10 days) diazepam
      treatments decreased hippocampal dialysate 5-HT (but not 5-HIAA) concentrations
      in freely moving rats, suggesting decreased availability of 5-HT to receptors.
      Twenty-four hours after the last chronic diazepam injection, hippocampal
      dialysate 5-HT did not differ from that in vehicle-treated rats. However,
      although reduced 5-HT availability often increases postsynaptic 5-HT receptor
      mediated responses, the anxiogenic effect of m-chlorophenylpiperazine (mCPP),
      which is mediated by the activation of postsynaptic 5-HT(2C) receptors, was not
      increased (as indicated by the elevated plus-maze test) when given 2 days after
      10 days of chronic diazepam, in intact rats. Nevertheless, concurrently in that
      test, significantly increased anxiety occurred after withdrawal from chronic
      diazepam (10mg/kg/day x 10 days). The results suggest that benzodiazepine
      withdrawal-induced anxiety is not mediated by changes in 5-HT(2C) receptor
      sensitivity, and may be independent of the benzodiazepine-induced reduction of 5
      HT release in the rat hippocampus.

PMID- 11224411
TI  - Examining the subjective, psychomotor and reinforcing effects of nitrous oxide in
      healthy volunteers: a dose-response analysis.
AB  - The present study examined the subjective, psychomotor and reinforcing effects of
      10%, 20%, 30% and 40% nitrous oxide in oxygen in 16 healthy volunteers using a
      choice procedure in which sampling (e.g. 20% nitrous oxide and oxygen-placebo)
      and choice trials (e.g. 20% nitrous oxide vs. oxygen placebo) were within the
      same session. Across the four-session study, nitrous oxide dose was varied.
      Nitrous oxide in a dose-related manner altered subjective effects (e.g. increased
      visual analog scale ratings of "high", "stimulated" and "tingling") and decreased
      performance on the Digit Symbol Substitution Test. 10%, 20%, 30% and 40% nitrous
      oxide were chosen over oxygen by 6, 7, 7 and 8 subjects, respectively. We
      conclude that nitrous oxide across a range of subanesthetic doses did not
      function as reinforcer in the majority of subjects tested.

PMID- 11224412
TI  - Effect of multiple discrimination reversals on acquisition of a drug
      discrimination task in rats.
AB  - There are many similarities between exteroceptive stimuli and interoceptive
      stimuli. Nevertheless, it has been suggested that behavior maintained by drug
      stimuli might be more difficult to reverse than behavior controlled by
      exteroceptive stimuli. Once a discrimination is established with an exteroceptive
      stimulus, it can be reversed by switching the reinforcement contingencies, and
      repeated reversals result in progressively faster relearning of the
      discrimination. To determine whether faster relearning of successive
      discrimination reversals also occurs when the discrimination is controlled by an
      internal drug stimulus, we trained rats to discriminate 3.2mg/kg phencyclidine
      (PCP) from saline, in a two-lever food-reinforced operant task. After this
      discrimination was acquired, the reinforcement contingencies were reversed. A
      number of such discrimination reversals were performed to determine whether fewer
      trials would be needed to reach criterion performance with each reversal. Each
      time the reinforcement contingencies were switched, fewer training sessions were
      required for the subjects to reach criterion. These results are similar to those
      observed when a discrimination has been established with exteroceptive stimuli.
      The present study provides further evidence of the similarity between
      interoceptive drug stimuli and exteroceptive sensory stimuli.

PMID- 11224413
TI  - Opioids and rate of positively reinforced behavior: differential antagonism by
      naltrexone.
AB  - Lever pressing by rats was maintained under a fixed-ratio 30 schedule of food
      presentation. The response rate-decreasing effects of several opioid compounds
      that vary in selectivity for, and activity at, u, kappa, and non-opioid
      receptors, were examined alone and in combination with the opioid antagonist
      naltrexone. Naltrexone (0.01-1.0mg/kg) produced dose-dependent and generally
      parallel rightward shifts in the dose-effect curves for morphine, fentanyl,
      butorphanol and nalbuphine. Apparent pA(2) values for naltrexone against these
      agonists ranged from 7.05 to 7.29, and the slopes of the regression lines fitted
      to the Schild plots approximated theoretical unity (-1.0), suggesting a
      competitive interaction at u-opioid receptors. In contrast, although at least one
      dose of naltrexone (0.01-10.0mg/kg) antagonized the response rate-decreasing
      effects of bremazocine, U50,488, (-)-pentazocine and nalorphine, suggesting some
      opioid activity, these effects differed from those of the u agonists in that: (a)
      they were less sensitive to naltrexone antagonism; (b) maximal rightward shifts
      were smaller; (c) antagonism patterns were not directly related to naltrexone
      dose and, in some cases, were influenced by the response rate-decreasing effects
      of the larger naltrexone doses; and (d) there were considerable between-subjects
      differences in sensitivity to naltrexone antagonism. Naltrexone (0.1-10.0mg/kg)
      did not antagonize the effects of the non-opioid control compound pentobarbital.
      The present results suggest that patterns of naltrexone antagonism can provide a
      basis for making inferences about receptor activity related to the effects of
      some opioids on rate of schedule-controlled behavior. With some opioids, however,
      such inferences are limited by the direct response rate-decreasing effects of
      naltrexone itself and by differences in patterns of antagonism across subjects.

PMID- 11224414
TI  - Effects of GR 68755 on d-amphetamine-induced changes in mood, cognitive
      performance, appetite, food preference, and caloric and macronutrient intake in
      humans.
AB  - Pre-clinical studies have suggested that 5-HT(3) antagonists such as GR 68755
      oppose mesocorticolimbic dopamine release, which may mediate the important
      effects of d-amphetamine on positive subjective mood, anorexia, and performance.
      Twenty-six healthy male volunteers received each of the following treatments in a
      double-blind, randomized, cross-over design separated by a period of four to
      seven days: (a) d-amphetamine (20mg orally); (b) placebo; (c) GR 68755 (2mg
      orally); and (d) GR 68755 plus d-amphetamine. Subjects completed subjective
      measures of mood, hunger, and satiety. Caloric and macronutrient intake were
      measured using a test meal. Performance and attention were assessed using
      standardized computerized tasks. GR 68755 enhanced accuracy on the computerized
      attention task but failed to reverse significantly any of the effects of d
      amphetamine. These results suggest that at these doses GR 68755 pre-treatment
      does not significantly reduce the effects of d-amphetamine.

PMID- 11224415
TI  - Behavioral tolerance and cross-tolerance to the response rate-decreasing effects
      of mu opioids in rats.
AB  - The present study was designed to characterize the degree of cross-tolerance
      between the response rate-decreasing effects of morphine and three mu opioids
      with varying relative intrinsic efficacies at the mu receptor, buprenorphine,
      butorphanol and fentanyl, and a non-opioid (+) amphetamine, in a behavioral
      tolerance paradigm. Lever pressing of rats was maintained by a fixed-ratio 20
      schedule of food presentation, and dose-effect curves for each drug were obtained
      prior to, during, and after daily administrations of morphine in separate groups
      of rats administered morphine either before (pre-session) or after (post-session)
      experimental sessions. Each of the mu opioids and the non-opioid (+)-amphetamine
      dose-dependently decreased response rates. In the pre-session group, daily
      administration of morphine shifted the morphine dose-effect curve 0.33 log unit
      rightward, indicating that tolerance had developed, and shifted the butorphanol
      dose-effect curve 0.96 log unit rightward. Daily pre-session administrations of
      morphine did not shift the dose-effect curves for buprenorphine, fentanyl, or (+)
      amphetamine. In the post-session group, daily administration of morphine did not
      shift the morphine, butorphanol, buprenorphine, fentanyl, or (+)-amphetamine dose
      effect curves. These data suggest that pharmacological variables, such as the
      drug's relative intrinsic efficacy at the mu receptor, can play a role in
      behavioral tolerance and cross-tolerance.

PMID- 11224416
TI  - The pattern of locomotor activity after cocaine treatment in the rat.
AB  - The present study used a computerised technique to assess the behavioural effects
      on locomotor activity of i.p. cocaine administration in the rat. This
      computerised method provides considerable information about various behavioural
      responses, as well as accuracy by measuring the frequency and duration of every
      behavioural event. Cocaine induced an increase in behavioural events related to
      motor activity, such as moving, sniffing and rearing, while standing was reduced.
      Cocaine increased the frequency of the behavioural responses recorded, but
      decreased their mean duration. No stereotyped behavioural element, such as head
      swinging, head bobbing, licking, stereotyped mouth moving or stereotyped
      sniffing, was recorded after cocaine treatment. Cocaine, unlike d-amphetamine,
      induced a specific behavioural pattern characterised predominantly at all doses
      by a stimulated motor activation involving an increase in moving and sniffing and
      a decrease in standing behaviour.

PMID- 11224417
TI  - Alpha-phenyl-tert-butyl-nitrone (PBN) reverses age-related maze learning
      performance and motor activity deficits in C57 BL/6 mice.
AB  - Two experiments were performed to study the effects of age and repeated
      administration of alpha-phenyl-tert-butyl-nitrone (PBN), the free radical spin
      trapping agent, upon spontaneous motor activity levels and radial arm maze
      performance in normal young (3 month old) and normal aged (15 month old) C57 BI/6
      mice. In Experiment 1, the aged mice were found to show reduced locomotor and
      rearing behaviour in comparison with the young mice. In the radial eight-arm maze
      learning task, the aged mice performed at a comparable level to the young mice
      during the first learning trial (Day 1) but made significantly more errors and
      showed longer total latencies during the second trial presented 24h later. In
      Experiment 2, the aged and young mice were subchronically administered either PBN
      at a dose of 50mg/kg, s.c. over 12 days, or saline. Spontaneous motor activity
      was tested 72h after the last injection. 36h later the first test trial in the
      radial arm maze was presented; this was followed after a further 24h by the
      second test trial. Subchronic treatment with PBN increased locomotion counts in
      the aged (15 month old) mice during the 60min test period, but decreased rearing
      during the first 30min of the test period. In the radial arm maze, the
      performance deficit shown during the second test trial by the aged mice was
      abolished by repeated PBN administration; both the number of errors and the
      latencies to all eight pellets were significantly reduced in the aged mice that
      received PBN. PBN did not exert any effects upon the performance of the young
      mice. These results, considered in conjunction with other studies using gerbils
      or rats, implicate the involvement of free radical species in the deterioration
      of function in the aged C57 BI/6 mouse.

PMID- 11224418
TI  - The enhancement of retention performance induced by picrotoxin in mice may be
      mediated through a release of endogenous vasopressin.
AB  - Male Swiss mice were tested 48h after training in a one-trial step-through
      inhibitory avoidance task. Immediately post-training i.p. injection of the GABA
      antagonist picrotoxin (0.3-3.0mg/kg), at nonconvulsive doses, induced a dose
      dependent modification of retention performance. The lower doses of picrotoxin
      (0.1-1.0mg/kg) enhanced retention, whereas the highest dose (3.0mg/kg) impaired
      retention. Picrotoxin did not affect response latencies in mice not given the
      footshock on the training trial, indicating that the actions of picrotoxin on
      retention performance were not due to nonspecific proactive effects on response
      latencies. The enhancing effects of picrotoxin (1.0mg/kg) on retention were time
      dependent, which suggests that picrotoxin enhanced storage of recently acquired
      information. The enhancement of retention induced by picrotoxin (1.0mg/kg) was
      prevented by the vasopressin receptor antagonist, AAVP (0.01ug/kg, s.c.)
      administered immediately after training, but prior to picrotoxin treatment. This
      dose of AAVP did not affect retention by itself, either under the standard
      experimental conditions, or in mice trained with a high footshock. Low
      subeffective doses of picrotoxin (0.1mg/kg, s.c.) administered immediately after
      training, and hypertonic saline (1ml of 0.5M NaCl, i.p.), given 10min after
      training, interacted to improve retention. Considered together, these findings
      suggest that the better retention performance induced by post-training
      administration of picrotoxin could result, at least in part, from an endogenous
      release of vasopressin.

PMID- 11224419
TI  - Contribution of individual differences to discriminative stimulus,
      antinociceptive and rate-decreasing effects of opioids: importance of the drug's
      relative intrinsic efficacy at the mu receptor.
AB  - Rats were trained to discriminate 3.0mg/kg morphine from water in a standard two
      lever drug discrimination procedure and tested in a hot water tail-withdrawal
      procedure. When tested with morphine, fentanyl, buprenorphine and butorphanol,
      individual animals showed a three- to ten-fold difference in the lowest dose that
      substituted completely for morphine, whereas 30- to 1000-fold differences were
      obtained with nalbuphine and levallorphan, respectively. Across repeated
      determinations, the dose-effect curves for morphine and nalbuphine remained
      relatively stable within an individual, suggesting that the profound individual
      differences with nalbuphine were not a consequence of variability in the dose
      effect curve. In addition, despite the extremely shallow group dose-effect curves
      obtained with nalbuphine and levallorphan, intermediate levels of drug
      appropriate responding were not evidenced in individual animals. In the tail
      withdrawal procedure, the doses of morphine and fentanyl required to produce the
      maximal levels of antinociception varied by approximately three-fold across
      individual rats. With butorphanol and nalbuphine, differences across animals were
      greater than 30-fold and 300-fold, respectively, whereas with levallorphan,
      substantial individual differences were observed in the maximal level of
      antinociception. Further analyses indicated that animals sensitive to the
      stimulus effects of nalbuphine and levallorphan were also sensitive to the
      antinociceptive effects of nalbuphine, levallorphan and butorphanol. In contrast
      to the individual differences obtained with the stimulus and antinociceptive
      effects of these opioids, the potency of these drugs for decreasing rate of
      responding was similar across animals. These findings indicate that the relative
      efficacy of an opioid at the mu receptor is an important determinant of
      individual differences in responsiveness to its stimulus and antinociceptive
      effects, but not to its rate-decreasing effects.

PMID- 11224420
TI  - Pentobarbital discrimination and generalization to other drugs under multiple
      fixed-ratio fixed-interval schedules.
AB  - Pigeons were trained to discriminate 5mg/kg pentobarbital from saline under
      several multiple fixed-ratio fixed-interval schedules of food presentation. The
      following schedules were studied: multiple fixed-ratio 40 fixed-interval 18s
      (mult FR40 FI18), mult FR10 FI18s, mult FR10 FI180s and mult FR90 FI10s. After
      responding stabilized under each multiple schedule, generalization curves were
      determined for pentobarbital, amobarbital, diazepam, phencyclidine and d
      amphetamine. Pentobarbital generated dose-dependent increases in responding under
      all schedule components; however, there was more responding on the drug key after
      low doses of pentobarbital under FI components than under FR components, except
      for the FR90 component of the mult FR90 FI10 schedule. This tendency for more
      responding on the drug key after low doses of pentobarbital under FI components
      than under FR components generally was observed for low doses of all of the
      drugs. Examination of data from individual subjects revealed that there was a
      greater tendency for birds to distribute responding on both keys (mixed
      responding) under FI components than under FR components, where responding after
      each dose was confined largely to one of the two response keys. Analysis of local
      rates of responding within the FI component of the schedules showed that
      responding under the FI components developed the typical FI scallop at all FI
      component durations. These data suggest that FI schedules with values between 10
      and 180s generate similar dose-effect curves with higher rates of responding on
      the drug key after low doses of drugs than under FR schedules with low response
      requirements; however, under schedules with higher FR requirements, the dose
      effect curves for some drugs begin to look more like those under FI schedules.

PMID- 11224421
TI  - Mianserin enhancement of ethanol-induced conditioned place preference.
AB  - This experiment examined the influence of mianserin, a 5-HT(2) receptor
      antagonist, on the rewarding effect of ethanol in a place conditioning paradigm.
      Swiss-Webster mice received four pairings of a tactile stimulus with drug
      treatment consisting of two i.p. injections separated by a 30min interval. Drug
      treatment groups were as follows: saline (10mg/kg) followed by ethanol (2mg/kg);
      mianserin (10mg/kg) followed by ethanol; mianserin followed by saline. A
      different stimulus was paired with two saline injections. During conditioning,
      ethanol produced increases in locomotor activity that were reduced by mianserin.
      Mianserin alone reduced activity levels. As expected, group saline-ethanol showed
      a nonsignificant trend towards conditioned place preference. However, mianserin
      enhanced the acquisition of ethanol preference, whereas mianserin alone did not
      produce either place preference or aversion. The results are consistent with the
      notion that serotonergic systems are important in the response to ethanol, and
      further suggest that 5-HT(2) receptor blockade increases the rewarding effects of
      ethanol.

PMID- 11224422
TI  - Involvement of GABA(B) receptors in the motor inhibition produced by agonists of
      brain cannabinoid receptors.
AB  - The present study was designed to investigate the possibility of activation of
      GABA(B) receptors during the motor inhibition caused by cannabimimetics. Adult
      male rats were injected with an acute dose of arachidonylethanolamide (AEA),
      Delta(9)- tetrahydrocannabinol (THC), beclofen or vehicle, after pretreatment
      with CGP 35348, a specific antagonist for GABA(B) receptors, or vehicle, and the
      behavioral response produced by these compounds tested in an open field. As
      expected, the administration of either AEA or THC produced a very pronounced
      motor inhibition, reflected by decreased ambulation and increased time spent in
      inactivity. The administration of baclofen also produced a marked motor deficit,
      with similar changes to those observed with both cannabimimetics. Pretreatment
      with the GABA(B) antagonist, CGP 35348, prevented the motor inhibition induced by
      baclofen and also attenuated the motor deficit caused by both cannabimimetics,
      suggesting a role for this receptor. In summary, a GABAergic influence, acting
      through GABA(B) receptors, seems to be involved in mediating motor effects of
      cannabimimetics, since the blockade of these receptors attenuates cannabimimetic
      induced signs of motor inhibition.

PMID- 11224423
TI  - Classically conditioned motor effects do not occur with cocaine in an unbiased
      conditioned place preferences procedure.
AB  - Classical conditioning and behavioural sensitisation of motor activity induced
      with cocaine (10mg/kg, i.p.) were examined using an unbiased two-compartment
      conditioned place preference (CPP) procedure. Habituation of the rats to the
      testing environment prior to training was varied (i.e. either the rats were
      habituated to the environment for three 30min sessions or they were not) in order
      to examine a possible influence of latent inhibition on conditioned locomotion or
      behavioural sensitisation. Furthermore, rats were either trained with an explicit
      CS+ (cocaine-paired compartment) and CS- (vehicle-paired compartment), or else
      they were trained with no barrier between the compartments (effectively a single
      compartment procedure with no explicit CS-) in order to examine a possible
      influence of stimulus change (training rats while confined to one compartment,
      but testing with no barrier between compartments). On a drug-free test day with
      free access to both compartments, rats previously exposed to cocaine in one
      compartment (CS+) and vehicle in the second compartment (CS-) spent more time in
      the CS+ compartment (conditioned place preference). However, under no
      circumstance was the rate of motor activity higher in the CS+ compartment than in
      the CS- compartment, as would be expected if cocaine-induced motor activity was
      classically conditioned to contextual cues. Whether or not increased activity
      extinguished with repeated drug-free exposures to previously drug-paired contexts
      depended on habituation experience. In addition, both habituation and current
      access to compartments (free or restricted) determined the presence of post
      extinction sensitisation to a challenge dose of cocaine (7.5mg/kg). Classical
      conditioning and non-associative sensitisation, independently or together, cannot
      account for this pattern of results.

PMID- 11224424
TI  - Intravenous self-injection of four novel phenethylamines in baboons.
AB  - The present study evaluated the intravenous self-administration of four
      substituted phenethylamines, using a substitution procedure in baboons. Baboons
      were trained to self-inject 0.32mg/kg/injection cocaine under a fixed-ration (FR)
      schedule, with a 3h timeout following each injection. Doses of (+/-)-N-ethyl-3, 4
      methylenedioxyamphetamine HCI (MDE), (+/-)-N-hydroxy-3, 4
      methylendioxyamphetamine HCI (N-OH-MDA), (+)-N-N-dimethylamphetamine HCI (NNDMA),
      and 4-bromo-2,5-dimethyoxy-beta-phenethylamine (BDMPEA) and their vehicles were
      substituted for cocaine for 15 or more successive days. High doses of MDE and N
      OH-MDA maintained self-injection; however, NNDMA and BDMPEA self-injection was
      less consistent. NNDMA did not reliably maintain self-injection, whereas one or
      more doses of BDMPEA maintained self-injection in each of three baboons.
      Intermediate to high doses of all four compounds decreased food pellet intake
      maintained under a FR schedule of reinforcement on a different lever. In some
      baboons, high doses of N-OH-MDA, NNDMA and BDMPEA produced signs of behavioral
      toxicity (e.g. cyclic pattern of self-injection, behavioral agitation,
      stereotypical movements) that were similar to those previously observed after
      administration of high doses of classic psychomotor stimulants such as d
      amphetamine; however, the severity and profile of this behavioral toxicity
      differed between compounds. Thus, the present study documents both similarities
      and differences in the behavioral profiles of these four phenethylamines.

PMID- 11224425
TI  - Relations between dose magnitude, subject sensitivity, and the development of
      tolerance to cocaine-induced behavioral disruptions in pigeons.
AB  - Keypecking by 12 pigeons, maintained by a fixed-ratio 30 schedule of food
      presentation, was decreased in rate by acute pre-session injections of cocaine in
      a dose-dependent manner, with larger doses producing more disruption. A constant
      dose of cocaine was then injected prior to every session for 40 days. Some
      subjects received a relatively small dose, some received a medium-sized dose, and
      others received a large dose. Subsequently, dose-effects were reassessed via once
      weekly probe injections, with every other session continuing to be preceded by
      injection of the daily dose of cocaine. Then a different dose of cocaine was
      administered daily for 40 more days, after which the dose-effect function was
      redetermined in like manner. In general, tolerance to cocaine-induced response
      rate reductions was most likely to develop when (a) the repeatedly-administered
      dose of cocaine was relatively small (even without acute effect on keypecking)
      and (b) the subject's keypecking was disrupted by smaller doses of cocaine in the
      initial dose-effect assessment. Tolerance was generally observed as a shift in
      the dose-effect function that, in several cases, could be eliminated by
      increasing the magnitude of the daily administered dose. In addition, every
      subject's rate of keypecking following saline injections was lowered after daily
      exposure to cocaine. These results (a) are partially consistent with the
      reinforcement-loss account of tolerance to cocaine-induced behavioral
      disruptions, and (b) support previous observations of withdrawal symptoms
      following cessation of extended exposure to cocaine.

PMID- 11224426
TI  - Modification of naloxone-precipitated withdrawal symptoms in mice by drugs acting
      on alpha(2)-adrenoceptors.
AB  - Modification of naloxone-precipitated withdrawal symptoms by drugs acting on
      alpha-adrenoceptors was investigated in morphine-dependent mice. Clonidine (0.05
      1mg/kg) attenuated most withdrawal symptoms, but potentiated withdrawal
      hypothermia. Jumping was attenuated by doses of clonidine up to 0.3mg/kg, but
      markedly potentiated by 1mg/kg. Prazosin (0.05mg/kg) neither had effects of its
      own, nor influenced those of clonidine. Both yohimbine (0.05-5mg/kg) and idazoxan
      (1-10mg/kg) potentiated naloxone-precipitated withdrawal symptoms. When tested
      against a low dose of clonidine (0.2mg/kg), idazoxan dose-dependently reduced the
      suppressive effects of clonidine on jumping, "wet dog" shakes, burrowing and body
      weight loss but potentiated the hypothermic response of clonidine. Yohimbine
      similarly reduced the suppressive effect of clonidine on body-weight loss and
      potentiated its hypothermic response, but unlike idazoxan, it did not influence
      the inhibition by clonidine of "wet dog" shakes, and markedly reversed the
      suppression of jumping and burrowing into potentiation. Yohimbine and idazoxan
      also differed with respect to their antagonistic profile against a high dose of
      clonidine (1mg/kg). Yohimbine further aggravated the potentiation of jumping by
      clonidine, reduced the effect on body-weight loss and reversed the suppression of
      burrowing by clonidine. On the other hand, idazoxan markedly reduced the
      potentiation of jumping by clonidine, and reversed its effect on "wet dog" shakes
      and burrowing. These findings indicate that clonidine has a biphasic effect on
      jumping, and disclose differences in the antagonistic profiles between yohimbine
      and idazoxan. The results suggest that in addition to alpha(2)-adrenoceptors, non
      adrenergic imidazoline receptors sensitive to clonidine and idazoxan but not to
      yohimbine may modulate the expression of morphine withdrawal symptoms.

PMID- 11224427
TI  - Sequential involvement of NMDA receptor-dependent processes in hippocampus,
      amygdala, entorhinal cortex and parietal cortex in memory processing.
AB  - Rats bilaterally implanted with cannulae in the CA1 region of the dorsal
      hippocampus and/or in the amygdaloid nucleus, in the entorhinal cortex, and in
      the posterior parietal cortex, were trained in a step-down inhibitory avoidance
      task. At various times after training (immediately, 30, 60 or 90min) they
      received, through the cannulae, 0.5ul microinfusions of saline or of 5.0ug of AP5
      dissolved in saline. A retention test was carried out 24h after training.
      Retention test performance was hindered by AP5 given into hippocampus, amygdala,
      or both hippocampus and amygdala immediately but not 30min post-training. The
      drug was amnestic when given into the entorhinal cortex 30, 60 or 90min after
      training, or into the parietal cortex 60 or 90min after training, but not at
      earlier times. The findings suggest a sequential entry in operation, in the post
      training period, of NMDA-receptor mediated mechanisms involved in memory
      processing; first in hippocampus and amygdala, 30min later in entorhinal cortex,
      and 30min later in posterior parietal cortex.

PMID- 11224428
TI  - Stimulus properties of the L-type calcium channel agonist BAY k 8644 in rats.
AB  - Calcium (Ca(2+)) channels appear to be involved in the regulation of ethanol
      (EtOH) intake, as indicated by the effectiveness of both L-type Ca(2+) channel
      antagonists and agonists in reducing EtOH intake in animals. The present study
      was aimed to investigate rewarding/aversive and discriminative stimulus effects
      of the Ca(2+) channel agonist BAY k 8644, a compound showing pronounced anti
      alcohol effects in rats. Therefore, a series of conditioned taste aversion (CTA),
      conditioned place preference (CPP) and two-lever drug discrimination (DD)
      experiments were conducted in Wistar rats, with (+/-)-BAY k 8644 and its
      enantiomers. After i.p. application, (+/-)-BAY k 8644 (0.0625-1mg/kg), (-)-BAY k
      8644 (0.125-1mg/kg) and (+)-BAY k 8644 (2.5-20mg/kg) all induced a dose-dependent
      CTA. The minimal effective doses (MED) for (+/-)-, (-)- and (+)-BAY k 8644 were
      0.25, 0.25 and 10mg/kg, respectively. In a CPP study, however, (+/-)-BAY k 8644
      (0.25-2mg/kg, i.p.) showed neither aversive nor rewarding stimulus properties.
      Rats were trained to discriminate (-)-BAY k 8644 (0.3mg/kg, i.p.), the enantiomer
      acting as a high potency Ca(2+) channel agonist, from vehicle, in a two-lever DD
      procedure (ED(50)) value: 0.05mg/kg); full generalisation: 0.1mg/kg). The (-)-BAY
      k 8644 cue dose-dependently generalized to (+/-)-BAY k 8644 and (+)-BAY k 8644,
      the enantiomer acting as a low potency Ca(2+) channel antagonist, with ED(50)
      values of 0.06 and 0.28mg/kg, respectively. Both (+/-)- and (+)-BAY k 8644
      produced full generalization at 1mg/kg, the latter compound showing an inverted U
      shaped curve (i.e., this was the only dose showing >80% drug lever selection).
      The stimulus patterns of BAY k 8644 and its enantiomers appear to resemble the
      anti-alcohol profiles of these compounds. Therefore, commonalities between the
      stimulus properties of the agonistic and antagonistic enantiomers might provide a
      clue for the mechanism underlying the anti-alcohol effects of L-type Ca(2+)
      channel antagonists and agonists.

PMID- 11224429
TI  - Effects of mood manipulation on subjective and behavioural measures of cigarette
      craving.
AB  - Cigarette cravings were evaluated in a sample of moderately heavy smokers, using
      the Questionnaire on Smoking Urges (QSU), and a progressive-ratio (PR) operant
      procedure in which responding on a computer keyboard was reinforced by puffs on a
      cigarette, under a progressively increasing work requirement. Subjects were also
      exposed to musical mood-induction procedures: the induction and maintenance of
      depressed and elated mood states was confirmed by visual analogue scales and a
      mood questionnaire. Smoking did not alter mood state. However, relative to the
      elated condition, induction of a depressed mood caused increases in both QSU
      scores and measures of PR performance. The results provide the first experimental
      confirmation of a causal relationship between depressed mood and cigarette
      craving.

PMID- 11224430
TI  - Training dose as a decisive factor for discrimination of a drug mixture in rats.
AB  - The impact of training dose on the characteristics of a discrimination maintained
      by a mixture of two dissimilar drugs has been investigated in order to refine
      this approach to the study of drug interactions. Three groups of rats (n = 10)
      were trained to discriminate mixtures of (+)-amphetamine (0.2-0.8mg/kg) plus
      pentobarbitone (5-20mg/kg) from saline, in a two-lever operant procedure with
      food reinforcement, with the ratio of the doses held constant (amphetamine:
      pentobarbitone, 1:25). Discriminations were acquired to an accuracy of 90-97%.
      There was full generalisation to amphetamine alone, but only in rats trained with
      mixtures of the smaller doses of the single drugs. There was partial
      generalisation when either apomorphine (50%) or nicotine (63%) was administered
      alone, and the magnitude of these responses was inversely related to the dose of
      mixture used for training. Doses of pentobarbitone half of those used for
      training produced little discriminative response when administered alone to rats
      trained with the two smallest doses of the mixture; the same doses of
      pentobarbitone increased responses to amphetamine or apomorphine in a more than
      additive manner. Strikingly, some doses of apomorphine and pentobarbitone that
      did not generalise when administered separately, produced full generalisation
      when administered together, but only in rats trained with the smaller doses of
      the mixture. In contrast, pentobarbitone did not enhance generalisation to
      nicotine in any group. It was concluded that, on the one hand, patterns of
      generalisation to single drugs followed an orderly pattern resembling those for
      discriminations established with single drugs. On the other hand, there was a
      complex pattern of generalization from one mixture to another; thus, altering the
      doses of drugs used for training markedly influenced discriminations of an abused
      drug mixture, but no simple rules to predict the influence of training dose have
      been ascertained.

PMID- 11224431
TI  - The differential role of A1 and A2 adenosine receptor subtypes in locomotor
      activity and place conditioning in rats.
AB  - Previous studies have demonstrated that the non-specific adenosine antagonist
      caffeine possesses both motor activating and rewarding properties in a place
      conditioning paradigm. The present experiments were designed to determine the
      relative contribution of A1 and A2 adenosine receptor subtypes to these effects.
      The A2 adenosine antagonist CGS 15943A (0.1-10.0mg/kg) dose-dependently produced
      both a place preference and enhanced locomotor activity. In contrast, the A1
      antagonist CPX (0.01-40.0mg/kg) failed significantly to alter either behavioral
      measure. Both the A1 receptor agonist CPA (0.01-10.0mg/kg) and the A2 receptor
      agonist CGS 21680 (0.01-1.0mg/kg) reliably decreased activity but failed to
      produce significant place conditioning. The increased activity produced by the A2
      antagonist CGS 15943A (1.0mg/kg) was attenuated by behaviourally active doses of
      either CPA or CGS 21680. The place preference produced by CGS 15943A (1.0mg/kg)
      was attenuated by CPA and CGS 21680, at agonist doses that failed to produce
      place conditioning when administered alone. In general, the results suggested
      that although it is the A2 receptor subtype that participates in the
      establishment of place conditioning and enhanced activity, both receptors
      participate in the diffuse depressant effects associated with adenosine.

PMID- 11224432
TI  - Pentobarbital, diazepam and phencyclidine disrupt delayed matching performance:
      interactions with picrotoxin in pigeons and squirrel monkeys.
AB  - The ability of picrotoxin to antagonize selectively the effects of pentobarbital
      was investigated in pigeons and squirrel monkeys responding under a titrating
      matching-to-sample schedule of reinforcement. Under the titrating matching-to
      sample baseline, the length of the delay changed as a function of the animal's
      matching accuracy. Picrotoxin (0.03-1mg/kg) failed to alter significantly the
      matching accuracy of pigeons; however, rate of responding was markedly suppressed
      at a dose of 1mg/kg. In squirrel monkeys responding under a similar schedule,
      picrotoxin (0.001-0.3mg/kg) was without significant effect. Selected doses of
      picrotoxin in both pigeons (0.3 and 0.56mg/kg) and squirrel monkeys (0.1 and
      0.3mg/kg) failed to shift the pentobarbital or diazepam dose-response curve for
      mean delay length to the right. However, in both species, picrotoxin shifted the
      dose-response curve for pentobarbital on rate of responding to the right. No such
      shift was observed for the effect of diazepam on rate of responding. In both
      species, the combination of picrotoxin and phencyclidine shifted the dose
      response curves for phencyclidine on rate of responding, but not mean delay,
      downward and to the left, in an apparent additive manner. Thus, picrotoxin failed
      to produce a significant pharmacological antagonism of the effects of
      pentobarbital, diazepam or phencyclidine on matching accuracy. This failure to
      observe an antagonism of the effects of pentobarbital on matching accuracy, at
      doses of picrotoxin that antagonized the effects of pentobarbital on rate of
      responding, suggests that the effects of pentobarbital on matching accuracy and
      rate of responding are mediated by different receptor sites.

PMID- 11224433
TI  - Dexfenfluramine and 8-OH-DPAT modulate impulsivity in a delay-of-reward paradigm:
      implications for a correspondence with alcohol consumption.
AB  - Clinical studies identify impulsivity as a defining feature of an alcohol abuse
      syndrome. We recently reported an animal analogue: impulsivity assessed in a
      delay-of-reward paradigm strongly predicted magnitude of alcohol consumption. In
      this study we further explored this relationship. We asked whether serotonergic
      manipulations previously established to reduce and augment alcohol consumption
      would have corresponding effects on impulsivity in a delay-of-reward paradigm.
      This study revealed that two doses (1 and 2mg/kg) of dexfenfluramine, a
      serotonergic releaser known to reduce alcohol consumption, reduced choice of
      immediate reward, or impulsivity. We also found that three doses of the 5-HT(1A)
      agonist, 8-OH-DPAT, caused a biphasic dose effect on impulsivity. There was a
      clear dose-dependent progression from augmentation (6 and 31ug/kg) to a reduction
      (62ug/kg) of impulsivity scores. This effect mirrors a biphasic dose effect that
      has been found for alcohol intake. The findings suggest that impulsivity and
      alcohol consumption are intimately linked via common serotonergic pathways.

PMID- 11224434
TI  - Perspectives on cognitive psychopharmacology research.
AB  - This article discusses new perspectives in the psychopharmacology of cognition
      and analyses the advantages and disadvantages of using drugs as tools to study
      the mechanisms underlying memory functions. The use of 'stages' in the processing
      of information as a means for the analysis of cognitive operations is critically
      discussed as a rigid approach which can only partially accommodate different
      cognitive functions. Theoretical models of memory 'systems' and allocation of
      attentional resources are presented alongside findings from the two types of more
      commonly used drugs in cognitive psychopharmacology: the benzodiazepines (BZ) and
      the anticholinergics. In a post-hoc analysis of the effects of BZ and scopolamine
      on memory and attention, it has become clear that these newer theoretical models
      can accommodate most, but not all, of the effects of BZ and scopolamine on
      cognition. It is suggested that the development of cognitive tasks on the basis
      of these models and the execution of prospective studies with drugs as tools
      taking in to account the 'systems' approach to interpretation of data may be more
      useful for understanding cognitive functions.

PMID- 11224435
TI  - Should system or resource models replace stages models? Commentary on Duka et
      al., "Perspectives on Cognitive Psychopharmacology Research"

PMID- 11224436
TI  - Cognitive psychopharmacology research: a neuropsychological perspective.
      Commentary on Duka et al., "Perspectives on Cognitive Psychopharmacology
      Research"

PMID- 11224437
TI  - The influence of social structure on social isolation in amphetamine-treated Java
      monkeys (Macaca fascicularis).
AB  - Amphetamine-induced social isolation in monkeys has often been considered a valid
      animal model for certain negative symptoms of schizophrenia. However, there
      appear to be many ambiguities in relation to the exact nature of the isolation.
      Therefore, the effect of orally administered amphetamine (AMP) on the occurrence
      of social isolation in Java monkeys was studied. In part I the rank dependency of
      the effects of AMP (0.5mg/kg) was investigated in four alpha-males and three beta
      males. AMP increased 'proximity' and 'passive groom', and decreased 'active
      allogroom' in alpha-males. In contrast, AMP decreased all three behavioural
      elements to a certain extent in beta-males. It is concluded that AMP induces
      social isolation in beta-males, but not in alpha-males. In part II of this study
      the AMP-induced behaviour of the treated monkey and the simultaneously occurring
      changes in the non-treated monkeys were investigated in a detailed study of a
      single social group. AMP significantly reduced the frequency of 'exploration',
      'locomotion', 'self-groom', 'swing', 'active groom', 'inspect', 'approach' and
      originally-present stereotypies. Thus AMP apparently reduces the ability to
      initiate behaviour which is characteristic for the adult animal. AMP did not
      affect the frequency of 'present' and 'play' and enhanced that of 'aggression'
      and 'fear' in the beta-male; it also elicited various juvenile-like behaviours in
      both alpha- and beta-males, suggesting that AMP induces a behavioural regression.
      Furthermore, the behaviour of the non-treated monkeys of the group was decisive
      for the occurrence of social isolation of the treated monkey. Thus, the effects
      of AMP on the social behaviour of Java monkeys depend on the individual
      sensitivity, the social position which the subject occupies in its group, and the
      behaviour of the partners of the treated subject.

PMID- 11224438
TI  - Effect of naloxone on the long-term body weight gain induced by repeated
      postnatal stress in male mice.
AB  - Stress during the early postnatal life of laboratory animals can induce body
      weight gain in adulthood. Exposure of mice to repeated postnatal stress has been
      shown to increase body weight some weeks after the recording of a hyposensitivity
      to thermal nociceptive stimulation. Since the increase in nociceptive threshold
      after repeated environmental manipulations can be interpreted as a behavioral
      index of stress-induced endogenous opioid release, the present experiment was
      designed to study whether the stress-induced body weight gain could be prevented
      by a chronic treatment with the opioid antagonist naloxone. Sixteen litters of CD
      1 male mice were used. Treatments took place from day 2 to day 19 of postnatal
      life. As well as body weight we measured spontaneous motor activity and food and
      water consumption. Body length and epididymal fat pad weight were also measured,
      at the end of the experiment. Stress (i.e. a daily saline injection schedule)
      increased the rate of body weight gain and the epididymal fat pad weight; a daily
      injection schedule of naloxone did not induce these effects. No significant
      differences were evident among groups regarding body length, motor activity, or
      food and water intake. The data suggest that repeated postnatal saline injections
      may induce long-term modifications in body and epididymal fat weights and that
      these effects may be mediated by endogenous opioids.

PMID- 11224439
TI  - Changes in sensitivity to the rate-decreasing effects of opioids in pigeons
      treated acutely or chronically with nalbuphine.
AB  - This study examined whether tolerance or dependence develops to the effects of
      the low-efficacy u opioid agonist nalbuphine on schedule-controlled responding.
      In untreated pigeons responding under a fixed ratio (FR)-20 schedule of food
      presentation, nalbuphine, naltrexone, morphine, fentanyl, etonitazene and
      enadoline decreased response rates. Naltrexone (0.1-10.0mg/kg) did not antagonize
      the rate-decreasing effects of nalbuphine. In a separate group of pigeons,
      chronic nalbuphine treatment (1.0-56.0mg/kg/day) did not alter the sensitivity of
      pigeons to the rate-decreasing effects of nalbuphine or naltrexone. In pigeons
      treated with 56.0mg/kg/day of nalbuphine, dose-effect curves for u and kappa
      agonists were shifted 3- to 10-fold to the right of dose-effect curves determined
      prior to chronic treatment. The rate-decreasing effects of nalbuphine did not
      appear to be mediated by opioid receptors, as evidenced by the inability of
      naltrexone to antagonize nalbuphine and the lack of tolerance development.
      Although chronic nalbuphine altered the sensitivity to the rate-decreasing
      effects of u and kappa agonists, there was no change in sensitivity to
      naltrexone. To the extent that increased sensitivity to antagonists is indicative
      of dependence, these data suggest that opioid dependence does not develop to
      nalbuphine.

PMID- 11224440
TI  - Differential involvement of D1 and D2 dopamine receptors in the expression of
      morphine withdrawal signs in rats.
AB  - The role of dopamine (DA) receptors in the expression of opioid dependence was
      examined by use of an unbiased conditioned place preference paradigm. Male
      Sprague-Dawley rats were implanted s.c. with two pellets containing placebo or
      75mg morphine. Animals received one conditioning session with saline and one with
      the DA D1 receptor antagonist SCH23390 (0.01-0.05mg, s.c.) or the DA D2 receptor
      antagonist raclopride (0.25-1.0mg/kg, s.c.). Conditioning sessions were conducted
      4 days after pellet implantation. During each of these sessions, physical signs
      of withdrawal were quantified. In morphine-pelleted animals, the D2 receptor
      antagonist raclopride produced conditioned place aversions, with a minimum
      effective dose of 0.5mg/kg. Administration of a higher dose also resulted in wet
      dog shakes, ptosis and diarrhea in morphine-pelleted animals. This effect was not
      observed in response to lower doses of raclopride or in placebo-pelleted animals.
      The D1 receptor antagonist SCH23390 failed to produce conditioned place aversions
      in either morphine- or placebo-pelleted animals after single-trial conditioning.
      This antagonist was also ineffective in producing physical withdrawal signs.
      After two conditioning sessions with SCH23390, both the morphine- and placebo
      pelleted animals exhibited a marked aversion for the SCH23390-paired place.
      However, there was no difference between groups in the magnitude of this effect.
      These data demonstrate that the acute blockade of D2 receptors produces aversive
      effects in opioid-dependent animals and that this effect occurs in the presence
      of few, if any, prototypic physical withdrawal signs. Furthermore, the inability
      of a selective D1 receptor antagonist to produce conditioned aversive effects or
      physical signs of withdrawal suggests an important role of D2 as compared to D1
      receptors in the expression of morphine withdrawal signs.

PMID- 11224441
TI  - The benzodiazepine partial receptor agonist, bretazenil, provokes a strong
      hyperphagic response: a meal pattern analysis in free feeding rats.
AB  - In this report we characterize the effects of the benzodiazepine receptor partial
      agonist bretazenil (0.1-3mg/kg) on meal patterning and satiety sequences of male
      rats. Experiment 1 indicated that bretazenil (0.3-1.0mg/kg) doubled the size of
      the first meal; there was no concurrent increase in feeding rate and effects on
      water intake were smaller. Experiment 2 showed that the benzodiazepine receptor
      antagonist ZK93426 (10mg/kg) blocked this effect on meal size; in addition
      ZK93426 reduced water intake in the first 2h following drug administration, which
      we attribute to its weak inverse agonist action. Experiment 3 examined satiety
      sequences after bretazenil treatment. Food intake and feeding behaviour were
      enhanced; in the following behavioural sequence, active and grooming behaviour
      patterns were reduced and resting was greatly increased. The data are discussed
      in relation to current theories of benzodiazepine action on food intake and the
      processing of taste stimuli.

PMID- 11224442
TI  - Hypothermia and the 5-HT syndrome induced by CGS 12066B independently of 5-HT(1B)
      receptor activation.
AB  - The effects of CGS 12066B (3-14mg/kg), a putative 5-HT(1B) agonist, on 5-HT
      behavioral syndrome, motor activity and body temperature, were investigated in
      rats. The animals were well adapted to the experimental conditions before
      testing, and data sampling started at the same hour for each rat. The highest
      dose of CGS 12066B clearly reduced body temperature and induced flat body posture
      and hindlimb abduction. No significant change was seen in motor activity. The CGS
      12066B-induced changes were not antagonized by 5-HT(1B) receptor antagonists, or
      antagonists at other 5-HT receptor. In fact, the 5-HT(1A) antagonist NAN-190 and
      especially the non-selective 5-HT antagonist methiothepin, with definite 5-HT(1B)
      receptor blocking properties, both potentiated the decrease in body temperature.
      The findings suggest that the behavioral and body temperature effects of CGS
      12066B are not easily explained by 5-HT(1B) receptor stimulation, but may be
      mediated by activation of non-serotonergic mechanisms. Similar conclusions in
      studies with other 5-HT(1B) agonists suggest a common problem with such drugs.

PMID- 11224443
TI  - Acute effects of morphine on Substance P concentrations in microdissected regions
      of guinea-pig brain.
AB  - The present study investigated the effects of acute morphine treatment and of
      naloxone-induced morphine withdrawal on Substance P (SP) concentrations in
      microdissected regions of the guinea-pig brain. Guinea-pigs, which were treated
      with a single dose of morphine sulphate (15mg/kg s.c.), received naloxone
      hydrochloride (15mg/kg s.c.) after 2h. Control animals received injections of
      saline, saline and naloxone, or morphine and saline. Locomotor and behavioural
      activities were measured throughout the experiments. Animals were killed 0.5h
      after naloxone administration, brains were removed and SP-like immunoreactivity
      (SP-LI) was measured in microdissected regions using radioimmunoassay. Morphine
      significantly increased the concentration of SP-LI in the central nucleus of the
      amygdala, but reduced SP-LI overall in the mesencephalon. Guinea-pigs pretreated
      with morphine and then given naloxone to precipitate withdrawal showed no change
      in SP-LI concentrations in any brain region, compared with control animals,
      despite an increase in locomotor activity and other behaviours characteristic of
      opioid withdrawal in guinea-pigs.

PMID- 11224444
TI  - Evidence for a role for dopamine D3 receptors in the effects of dopamine agonists
      on operant behaviour in rats.
AB  - Several dopamine (DA) agonists have been reported to show some D3 versus D2
      selectivity but the extent of this selectivity depends on experimental
      conditions, and the behavioural effects of these compounds seem to differ little
      from those of non-selective agonists such as apomorphine. However, some recent
      studies have reported stronger correlations between several behavioural responses
      and D3 affinities than between the same responses and affinities for D2
      receptors. In the present study rats were trained to lever press for food on a
      fixed-ratio (FR10) schedule during daily 15min sessions. The DA agonists
      apomorphine; quinelorane; quinpirole; 7-hydroxy-2-(di-n-propylamino)-tetralin
      [(+/-)7-OH-DPAT]; (+)-(4aR, 10bR)-4-propyl-3, 4,4a, 10b-tetrahydro-2H,5H-1
      benzopyrano [4,3-b], 4(oxazin-9-ol); bromocriptine; and (3-hydroxyphenyl)-N
      propylpiperidine produced dose-related decreases in these response rates. The
      potencies of these compounds correlated significantly with their published
      potencies to produce a functional D3 but not a functional D2 response
      (stimulation of mitogenesis in transfected cells). The rate-decreasing effects of
      7-OH-DPAT were antagonised by the benzamide antipsychotic agent amisulpride, at
      low doses (1 and 3mg/kg) which have been shown to exert preferential activity at
      presynaptic DA receptors. Haloperidol and remoxipride produced only small
      antagonist effects. These results are consistent with the view that D3 DA
      receptors may play an important role in mediating the behavioural effects of DA
      agonists and that these receptors have a presynaptic location.

PMID- 11224445
TI  - Impact of training history on discrimination of a drug mixture by rats.
AB  - The impact of training sequence on discrimination of a mixture of two drugs was
      investigated with five groups of rats (n = 10). In phase I, two groups were
      trained according to conventional two-lever, operant drug discrimination
      protocols with food reinforcement; one of these groups was trained with nicotine
      (0.4mg/kg) and the other group was trained with midazolam (0.15mg/kg). The three
      remaining groups served as controls and were subjected to 'sham' training in
      which administrations of saline, nicotine or midazolam were unrelated to
      contingencies of reinforcement. After completion of phase I (40 sessions), all
      five groups were trained to discriminate a mixture of nicotine (0.4mg/kg) plus
      midazolam (0.15mg/kg) from saline (phase II). Any differences between the groups
      in their performance during phase II could, therefore, be attributed to their
      different histories in phase I. During phase II, all groups discriminated the
      mixture from saline with similar accuracy (89-94% drug-appropriate responding
      after mixture as compared with 2-7% after saline). In the three groups of rats
      subjected to 'sham' training in phase I, there was partial generalization to both
      nicotine (45-53%) and midazolam (39-40%), each of which therefore contributed
      about equally to stimulus control by the mixture. In rats that were initially
      trained to discriminate nicotine, midazolam had acquired little stimulus control
      over behaviour (9%) and discrimination of the mixture was attributable largely to
      the nicotine (87%). Conversely, in rats that were initially trained to
      discriminate midazolam, nicotine contributed 3% and midazolam 76% to stimulus
      control by the mixture. These powerful, persistent effects of training sequence
      were interpreted as examples of associative blocking demonstrated with the
      interoceptive stimuli produced by psychoactive drugs.

PMID- 11224446
TI  - Opioids and rate of positively reinforced behavior: III. Antagonism by the long
      lasting kappa antagonist norbinaltorphimine.
AB  - Various opioid compounds were examined before and after administration of a 40ug
      (i.c.v.) dose of norbinaltorphimine (nor-BNI) in rats responding under a fixed
      ratio 20 schedule of food presentation. At time points ranging from 1 to 133 days
      after administration of nor-BNI, the dose-effect curve for the kappa opioid
      bremazocine was shifted to the right of that obtained prior to the administration
      of nor-BNI. The magnitude of these rightward shifts were somewhat larger at day
      14 than day 1, remained unchanged between days 14 and 49, and then declined
      between days 70 and 133. Nor-BNI also produced large rightward shifts in the dose
      effect curves for the kappa opioids U50,488, spiradoline and U69,593, and a small
      rightward shift in the curve for ethylketocyclazocine. In contrast, nor-BNI did
      not alter the dose-effect curves for (-)-n-allylnormetazocine, (-)-cyclazocine,
      nalorphine and the mu opioid morphine. The present findings indicate that the
      rate-decreasing effects of bremazocine, U50,488, U69,593, spiradoline and
      ethylketocyclazocine are mediated by agonist activity at the kappa opioid
      receptor(s). These findings also indicate that nor-BNI is a long-lasting and
      kappa opioid-selective antagonist that offers a number of advantages over
      naloxone and naltrexone as a pharmacological tool for examining the kappa opioid
      mediated activity of opioid compounds.

PMID- 11224447
TI  - Opposing effects of CCK(A) and CCK(B) antagonists on the development of
      conditioned activity in rats.
AB  - Cholecystokinin (CCK) is co-localized with dopamine (DA) in portions of the
      mesolimbic system. Evidence suggests that CCK(B) receptor mechanisms mediate an
      inhibitory effect on DA function while CCK(A) receptor mechanisms mediate a
      facilitory effect on DA function. As DA has been implicated in the acquisition of
      conditioned activity, the present experiments investigated the interaction
      between selective CCK(A) and CCK(B) receptor antagonists on the development of
      conditioned activity. Experiment 1 determined whether the CCK(B) receptor
      antagonist, L-365,260 (0.01, 0.1 and 1.0mg/kg, i.p.) would induce conditioned
      activity. Paired groups received four two-hour drug-environment pairings whereas
      Unpaired groups received the two stimuli explicitly unpaired. The group that
      received L-365,260 (0.mg/kg) paired with the test environment subsequently showed
      increased activity in that environment in a drug-free test day. Experiment 2
      examined the interaction of pre-treatment with the CCK(A) receptor antagonist,
      devazepide (0, 0.001, 0.01 and 0.1mg/kg) on the conditioned activity induced by L
      365,260 (0.1mg/kg). Devazepide impaired the acquisition of L-365,260 conditioned
      activity. These studies suggest that CCK mechanisms play a key role in the
      development of conditioned activity and extend previous research suggesting a bi
      directional function for CCK(A) and CCK(B) receptors.

PMID- 11224448
TI  - Effects of anticholinesterase drugs tacrine and E2020, the 5-HT(3) antagonist
      ondansetron, and the H(3) antagonist thioperamide, in models of cognition and
      cholinergic function.
AB  - This study presents a comparison between two inhibitors of acetylcholinesterase,
      tacrine and E2020 (Donepezil), the 5-HT(3) receptor antagonist ondansetron, and
      the H(3) receptor antagonist thioperamide, in models of cholinergic function and
      cognition in male, Lister hooded rats. The cognitive tests used were an operant
      VI20 task, the delayed match to position task (short-term memory) and the 5
      choice serial reaction time task (attention). Scopolamine (SCOP) (0.075mg/kg
      s.c.) was utilised in both the short-term memory and attention tasks to impair
      performance. Both tacrine (1-30mg/kg) and E2020 (1-10mg/kg) similarly produced
      overt cholinomimetic signs of likely central origin (hypothermia, tremor),
      although tacrine produced more profound peripheral cholinomimetic signs (miosis,
      secretory signs) than E2020. Tacrine (30mg/kg) and E2020 (10mg/kg) reduced the
      number of reinforcements gained in the VI20 schedule. Similarly, both drugs
      attenuated the SCOP-impairment models in the short-term memory and attention
      tasks (1-3mg/kg). Ondansetron (10ng/kg-1mg/kg) and thioperamide (0.2-10mg/kg)
      failed to elicit overt cholinomimetic signs or influence the number of food
      reinforcements gained in the VI20 schedule. Neither ondansetron nor thioperamide
      attenuated the SCOP-induced impairment in either cognitive task. From the present
      studies, both E2020 and tacrine showed a similar behavioural profile in the
      models used, although E2020 was about three times more potent. Furthermore, E2020
      but not tacrine appeared to show some discrimination in eliciting central and
      peripheral cholinomimetic signs. The failure of ondansetron and thioperamide to
      reverse a SCOP-induced deficit in these models is discussed.

PMID- 11224449
TI  - Intravenous self-administration of cathinone by rats.
AB  - Cathinone is the principal psychoactive constituent in leaves of the khat shrub.
      In some parts of the world, khat leaves are commonly chewed for their stimulant
      effects. While it has been demonstrated that rhesus monkeys will self-administer
      cathinone, there has been no demonstration of cathinone self-administration in
      rats. Two experiments were therefore conducted on rats fitted with intravenous
      catheters. On an FR 1 reinforcement schedule, the dose response curve for
      cathinone was shifted to the left of that for cocaine by a factor of
      approximately two. Within the sessions, cocaine infusions tended to be spaced
      evenly, whereas cathinone infusions were generally more frequent in the early
      portions of the session than later. In a second experiment, pretreatment with the
      dopamine D1-type receptor antagonist SCH 23390, at 10mg/kg, significantly
      increased the number of infusions obtained. Pretreatment with the D2-type
      receptor antagonist spiperone caused only a slight, non-significant increase in
      cathinone self-administration. These results demonstrate that cathinone is a
      potent reinforcer in rats and suggest a role for D1-type dopamine receptors in
      mediating its reinforcing effects.

PMID- 11224450
TI  - Does potency determine amnestic effects of benzodiazepines? A dose-response
      comparison of flunitrazepam and nitrazepam.
AB  - This study was designed to explore whether differences in the psychomotor,
      subjective and memory effects of different benzodiazepines (BDZ) relate to
      differences in their potencies. Two BDZs with similar kinetics but different
      potencies were compared. Flunitrazepam (0.5 and 1.0mg, nitrazepam (5 and 10mg) or
      placebo were administered to 50 healthy volunteers in a double-blind, parallel
      group design. Subjects completed a test battery before and 1.5h post-treatment.
      The higher dose of the more potent BDZ, flunitrazepam, impaired episodic memory
      in relation to placebo. In contrast, differences in psychomotor and subjective
      effects between BDZ were less clear. We conclude that a main caveat to the
      conclusion that potency plays a role in determining BDZ amnestic effects is the
      possible contribution of sedation and differential task sensitivities to apparent
      differential effects of BDZ compounds.

PMID- 11224451
TI  - Anticonflict effects of 5HT(1A) agonists in pigeons are dependent on the level of
      response suppression.
AB  - Anxiety is a phenomenon that has many different manifestations. In order to test
      whether or not agents targeted to treat anxiety may have the properties necessary
      to treat differing types of anxiety, we have studied a 8-OH DPAT, buspirone,
      LY228729, chlordiazepoxide and pentobarbital on three different punished
      responding procedures in pigeons. Procedure one was a fairly standard multiple
      FR30 FR30 punished responding model where responding into he punished component
      was suppressed by electric shock to 7-10% of responding in the unpunished
      component. Procedure two was similar except that responding during the punished
      component was suppressed more severely to 1-3% of control, using increased levels
      of shock. Procedure three was a VI30 schedule as the unpunished component, with
      concomitant FR5 shock in a second component, and concomitant FR20 shock in the
      third component. 5HT(1A) agonists, 8-OH DPAT, buspirone and LY228729 produced the
      typical large increases in punished responding in procedure one, were
      substantially less effective when shock levels were increased in procedure two,
      and produced differential results which were likely due to the schedule in
      procedure three. The more traditional anxiolytics, chlordiazepoxide and
      pentobarbital, were consistently effective across all three punished responding
      procedures. These results would seem to indicate that 5HT(1A) agonists may not be
      as broadly efficacious as traditional anxiolytics, and that the state or severity
      of anxiety may be an important variable to predict efficacy for 5HT(1A) agonists.

PMID- 11224452
TI  - The role of 5-HT(1A) receptors in the locomotor-suppressant effects of LSD: WAY
      100635 studies of 8-OH-DPAT, DOI and LSD in rats.
AB  - The selective 5-HT(1A) antagonist WAY-100635 was employed to further clarify the
      respective contributions of 5-HT(1A) receptors to the effects of the 5-HT(1A)
      agonist 8-OH-DPAT, the 5-HT(2) agonist DOI, and the mixed 5-HT(1A/2) agonist LSD
      on exploratory locomotion in rats. In nocturnal studies of well-handled rats
      during their first exposure to the Behavioral Pattern Monitor, which enables
      analyses of quantitative and qualitative changes in locomotor activity, locomotor
      and investigatory responses were reduced by treatment with either 8-OH-DPAT, DOI,
      or LSD. The hypoactivity produced by 8-OH-DPAT, but not that produced by DOI, was
      antagonized by pretreatment with WAY-100635. These results substantiate the
      effectiveness and functional specificity of WAY-100635 as a 5-HT(1A) antagonist.
      Furthermore, these results are inconsistent with a functional interaction between
      5-HT(1A) and 5-HT(2) receptors in the control of locomotor behavior. The
      decreases in locomotion produced by LSD were attenuated by pretreatment with WAY
      100635, indicating that the effects of LSD in this paradigm are due partly to
      agonist actions at 5-HT(1A) receptors. Therefore, 5-HT(1A) receptors appear to
      play a direct role in mediating the effects of LSD on rodent locomotion.

PMID- 11224453
TI  - The mouse defense test battery: evaluation of the effects of non-selective and BZ
      1 (omega1) selective, benzodiazepine receptor ligands.
AB  - The behavioral effects of several benzodiazepine (BZ) (omega) receptor ligands
      were compared using the Mouse Defense Test Battery which has been designed to
      assess defensive reactions of Swiss mice confronted with a natural threat (a rat)
      and situations associated with this threat. Primary measures taken before, during
      and after rat confrontation were escape attempts, flight, risk assessment and
      defensive threat and attack. The drugs used included non-selective BZ (omega)
      full (clonazepam, clorazepate, chlordiazepoxide and diazepam) and partial
      (bretazenil and imidazenil) agonists, and BZ-1 (omega1) selective (abecarnil, CL
      218,872 and zolpidem) receptor ligands. With the exception of clonazepam, non
      selective BZ (omega) receptor compounds only partially affected flight behaviors.
      The drugs reduced some but not all flight measures in response to the approaching
      rat, whereas clonazepam attenuated all flight reactions. In contrast to their
      mild and inconsistent actions on flight, the non-selective BZ (omega) receptor
      agonists displayed clear effects on risk assessment when subjects were chased by
      the rat. When contact was forced between the subject and the rat, the non
      selective BZ (omega) receptor full agonists reduced defensive threat and attack
      reactions, while the partial agonists imidazenil and bretazenil only weakly
      attenuated defensive attack behavior. Similarly, after the rat had been removed
      from the test area, the non-selective BZ (omega) receptor full agonists displayed
      greater efficacy than the partial agonists in reducing escape attempts. Overall,
      results obtained with the selective BZ-1 (omega1) receptor ligands demonstrated
      either no clear effects or no specific action on defensive reactions. Taken
      together, these data demonstrate that: (1) non-selective BZ (omega) agonists
      displaying high intrinsic activity affect a wider range of defensive behaviors
      than non-selective BZ (omega) receptor partial agonists; (2) the defense system
      does not involve primarily BZ (omega) receptors containing the alpha1-subunit.

PMID- 11224454
TI  - Disruption of learning by excitatory amino acid receptor antagonists.
AB  - Compounds that act as competitive or uncompetitive N-methyl-D-aspartate (NMDA)
      antagonists, glycine/NMDA-site antagonists, or alpha-amino-2,3-dihydro-5-methyl-3
      oxo-4-isoxalzolepropionic acid (AMPA)-receptor antagonists were evaluated for
      effects on a repeated acquisition of behavioral chains schedule by rats.
      Responding by rats was maintained by food presentation under a repeated
      acquisition or a performance procedure. Under the repeated acquisition procedure,
      subjects acquired a different three-response chain each daily session. Thus, each
      day a new learning curve could be generated for each animal thereby providing a
      repeated measure of learning. Food was presented under a second-order fixed-ratio
      three (FR3) schedule. Under the performance schedule rats responded under the
      same second-order FR3 schedule of food presentation: however, instead of a new
      sequence being presented each day, the same sequence of responding was required
      for each daily session. Both the competitive (CGS 19755) and uncompetitive
      (dizocilpine) NMDA antagonists distrupted repeated acquisition at doses that did
      not disrupt performance. In contrast, the glycine/NMDA antagonist MDL 104,653 or
      the competitive AMPA receptor antagonist LY 293558 did not disrupt acquisition or
      performance up to doses that suppressed responding. These results suggest there
      are different roles for various excitatory amino acid receptors, or sites on the
      NMDA receptor, in the neural bases of learning and that the disruption of
      acquisition by glutamate antagonists is dependent upon the particular receptor at
      which they have activity as well as the particular modulatory site of action.

PMID- 11224455
TI  - Integration of molecular biological techniques and behavioural pharmacology.
AB  - The rapidly advancing technology in the area of molecular neuroscience has
      greatly expanded the tools available to behavioural pharmacologists for
      investigating the molecular bases underlying the interrelation of pharmacological
      agents and behaviour. Strategies such as gene targeted knockout mutations,
      expression of an exogenous transgene, as well as the disruption of the cellular
      expression of genes with antisense oligonucleotides, are being successfully used
      to study normal and impaired behavioural function. Advantages of these genetic
      methods include the ability to manipulate systems for which selective
      pharmacological ligands do not exist, and the opportunity to study the
      interaction between genotype and environment without having to rely on
      spontaneously occurring mutants or selective breeding programmes. By targeting
      particular genes, questions can be asked about how genes control neuronal
      function and how manipulations of these genes affect behaviour. In particular,
      these strategies have been applied to studies of the molecular bases for
      disrupted behaviours, the behavioural actions of psychoactive drugs, and models
      of neuropsychiatric and neuropathological disorders. These emerging molecular
      biological techniques complement traditional pharmacological analysis to provide
      a very powerful approach with which to study the molecular correlates of
      behavioural pharmacology.

PMID- 11224456
TI  - Integration of molecular biological techniques and behavioural pharmacology:
      potentially valuable tools if used with care. Commentary on Gold's 'Integration
      of molecular biological techniques and behavioural pharmacology'

PMID- 11224457
TI  - Sense and sensibility. Commentary on Gold's 'Integration of molecular biological
      techniques and behavioural pharmacology'

PMID- 11224458
TI  - Integration of molecular biological techniques and behavioral pharmacology:
      rationale and impact. Commentary on Gold's 'Integration of molecular biological
      techniques and behavioural pharmacology'

PMID- 11224459
TI  - Transgenic superoxide dismutase mice: Increased mesolimbic u-opioid receptors
      results in greater opioid-induced stimulation and opioid-reinforced behavior.
AB  - Consequent to the insertion of the human Cu/Zn-superoxide dismutase (SOD)
      transgene, SOD transgenic mice (SOD-Tg) show higher concentrations of the primary
      receptor thought to be involved in opioid reinforcement (u). These increases are
      observed in areas specifically associated with the primary neurotransmitter
      thought to be involved in addiction (dopamine), and in neuroanatomical regions
      thought to mediate substance abuse (mesolimbic). In the present study we have
      tested the idea that these increases in u-receptors are associated with parallel
      changes in u-mediated behaviors. Baseline and morphine-induced locomotor activity
      were significantly altered in the SOD-Tg mice. A qualitative change in the nature
      of acute and chronic morphine-induced locomotor activity was demonstrated by a
      significant change in the slope of the dose-effect curve. SOD-Tg mice were
      significantly more sensitive to the locomotor stimulant effects of morphine.
      Intravenous morphine-reinforced behavior was also altered in the SOD-Tg mice. SOD
      Tg mice showed significant dose-related changes in operant lever-press responding
      maintained by morphine injection and significantly greater amounts of behavior
      were maintained by the drug than by vehicle under an intermittent schedule of
      reinforcement. In addition, SOD-Tg mice increased operant responding for the drug
      when the amount of behavior required to maintain drug intake increased 10-fold
      under a PR schedule of reinforcement. In contrast, in wild-type mice morphine
      injections failed to maintain greater amounts of behavior than vehicle, there
      were no dose-related changes in behavior, and when response requirements
      increased under the PR schedule, morphine intake decreased significantly. Thus,
      SOD transgene insertion significantly enhanced the efficacy of morphine as a
      reinforcer.

PMID- 11224461
TI  - Behaviorally relevant measures of glutamate transmission? Commentary on Di Chiara
      et al., 'Estimation of in-vivo neurotransmitter release by brain microdialysis:
      the issue of validity'

PMID- 11224460
TI  - Estimation of in-vivo neurotransmitter release by brain microdialysis: the issue
      of validity.
AB  - Although microdialysis is commonly understood as a method of sampling low
      molecular weight compounds in the extracellular compartment of tissues, this
      definition appears insufficient to specifically describe brain microdialysis of
      neurotransmitters. In fact, transmitter overflow from the brain into dialysates
      is critically dependent upon the composition of the perfusing Ringer. Therefore,
      the dialysing Ringer not only recovers the transmitter from the extracellular
      brain fluid but is a main determinant of its in-vivo release. Two types of brain
      microdialysis are distinguished: quantitative micro-dialysis and conventional
      microdialysis. Quantitative microdialysis provides an estimate of
      neurotransmitter concentrations in the extracellular fluid in contact with the
      probe. However, this information might poorly reflect the kinetics of
      neurotransmitter release in vivo. Conventional microdialysis involves perfusion
      at a constant rate with a transmitter-free Ringer, resulting in the formation of
      a steep neurotransmitter concentration gradient extending from the Ringer into
      the extracellular fluid. This artificial gradient might be critical for the
      ability of conventional microdialysis to detect and resolve phasic changes in
      neurotransmitter release taking place in the implanted area. On the basis of
      these characteristics, conventional microdialysis of neurotransmitters can be
      conceptualized as a model of the in-vivo release of neurotransmitters in the
      brain. As such, the criteria of face-validity, construct-validity and predictive
      validity should be applied to select the most appropriate experimental conditions
      for estimating neurotransmitter release in specific brain areas in relation to
      behaviour.

PMID- 11224462
TI  - Physiological relevance: a fundamental goal of brain microdialysis. Commentary on
      Di Chiara et al. 'Estimation of in-vivo neurotransmitter release by brain
      microdialysis: the issue of validity'

PMID- 11224463
TI  - Surgical anaesthesia with pentobarbital prevents the effect of local SCH 23390 on
      rat striatal acetylcholine release in a strain-dependent manner.
AB  - This study was performed in order to clarify existing discrepancies about the
      ability of the D1 antagonist SCH 23390 to reduce striatal acetyicholine (ACh)
      release after intrastriatal application by reverse dialysis. The possibility that
      negative findings were related to the use of pentobarbital rather than Equithesin
      as surgical anaesthesia for implanting microdialysis probes, and of Wistar rather
      than Sprague-Dawley rats, was tested. SCH 23390, applied by reverse dialysis at
      the concentration of 24uM, although able to reduce dialysate ACh in male Wistar
      rats implanted under Equithesin anaesthesia, failed to do so in rats of the same
      strain implanted 24h or 3 days earlier under pentobarbital anaesthesia. In male
      Sprague-Dawley rats, local SCH 23390 (24uM) reduced striatal dialysate ACh, both
      in rats implanted under Equithesin as well as in rats implanted under
      pentobarbital anaesthesia. Systemic SCH 23390 (0.3mg/kg s.c.) reduced dialysate A
      Ch both in Wistar and in Sprague-Dawley rats implanted under pentobarbital
      anaesthesia, but was more effective in the Sprague-Dawley strain. These
      observations, although consistent with a striatal localization of D1-receptors
      controlling ACh release, can be explained as being the result of a strain
      dependent barbiturate-induced inactivation of D1-mediated control of ACh
      transmission, which is potentiated by the local changes induced by microdialysis
      probe implant.

PMID- 11224464
TI  - Ethanol anticipation enhances dopamine efflux in the nucleus accumbens of alcohol
      preferring (P) but not Wistar rats.
AB  - It has been argued that the anticipation of ethanol consumption can activate
      reinforcement substrates involved in alcohol-seeking behavior. To test this
      hypothesis nucleus accumbens (NAc) dopamine (DA) efflux was monitored in alcohol
      preferring (P) and Wistar rats. Rats from each line were divided into two groups:
      one trained to self-administer 0.05% saccharin and the other trained to self
      administer 10% (w/v) ethanol. On the test day dopamine efflux was monitored in
      all animals during saccharin self-administration. In ethanol-expecting P rats,
      self-administration of saccharin produced a significant elevation in
      extracellular DA (150% of baseline within the first 15-20min). In contrast, a
      significant increase in extracellular DA was only observed during the final 30min
      of the test session in ethanol-expecting Wistar rats self-administering
      saccharin. The self-administration of saccharin in animals expecting the
      sweetener failed to elevate extracellular DA in both strains. Overall, these
      results suggest that the mere expectation of ethanol availability enhances the
      efflux of DA in the NAc of the P, but not the Wistar rat, which may play a role
      in the initiation or maintenance of ethanol seeking behavior in the P line.

PMID- 11224465
TI  - A critical assessment of electrochemical procedures applied to the measurement of
      dopamine and its metabolites during drug-induced and species-typical behaviours.
AB  - Monoamine neurotransmitters and their metabolites are electro-oxidizable at the
      surface of electrodes implanted in brain, and this has raised the expectation
      that in-vivo electrochemical procedures may be used routinely to monitor dynamic
      changes in dopamine (DA), noradrenaline and serotonin during species-typical and
      drug-induced behaviours. This expectation is slowly becoming a reality as various
      laboratories refine electrochemical procedures and design recording electrodes
      that are selective for specific neurotransmitters. The most important step is to
      conduct rigorous assessments of these procedures in-vivo to confirm that they are
      indeed valid and reliable bioprobes for a given neurochemical species. The
      present review describes the different electrochemical procedures and recording
      electrode designs currently used to measure monoamines in freely moving animals.
      Emphasis is placed on recording electrodes used to monitor DA in the
      extracellular compartment of the brain. In-vitro and in-vivo validation studies,
      demonstrating the selectivity and stability of these electrodes, are discussed in
      detail with respect to five criteria: (a) voltammograms recorded in-vivo are
      identical to those recorded in-vitro; (b) independent confirmation of the species
      detected and agreement of concentration estimates with other neurochemical
      methods; (c) sufficient electrode sensitivity to measure impulse-flow dependent
      transmitter efflux; (d) the dependency of the electrochemical signal on the
      presence of an intact neuronal system; and (e) predictable and reproducible
      effects of drugs or other manipulations on the electrochemical signal. The final
      section discusses recent applications of in-vivo electrochemical procedures for
      the monitoring of DA neurotransmission in terminal regions of the
      mesotelencephalic DA system during: (a) operant behaviour reinforced by brain
      stimulation reward or drugs of abuse; (b) species-typical motivated behaviours,
      as exemplified by feeding and sexual behaviour, and (c) in response to
      environmental stressors.

PMID- 11224466
TI  - Can voltammetric electrodes measure brain extracellular dopamine in the behaving
      animal? Commentary on Blaha and Phillips', 'A critical assessment of
      electrochemical procedures applied to the measurement of dopamine and its
      metabolites during drug-induced and species-typical behaviours'

PMID- 11224467
TI  - Changes in dopamine oxidation currents in the nucleus accumbens during unlimited
      access self-administration of d-amphetamine by rats.
AB  - In-vivo chronoamperometry in conjunction with stearate-modified carbon paste
      electrodes was used to monitor changes in dopamine (DA) oxidation currents in the
      nucleus accumbens during extended 24h and 48h sessions of i.v. self
      administration of d-amphetamine (0.1mg/infusion) by rats. Animals in two control
      groups received "yoked" administration of d-amphetamine or saline vehicle. In a
      separate experiment, microdialysis with probes adjacent to the electrochemical
      electrodes was employed to estimate the sensitivity of these electrodes to
      different extracellular concentrations of DA reverse dialyzed at the probe
      surface in the presence of pharmacological blockade of the DA transporter. During
      unlimited access to d-amphetamine self-administration, several distinct changes
      in basal DA oxidation currents were observed: 1) a significant elevation that
      peaked after asymptotically equal to 4h; 2) a steady decline to values that were
      not significantly different from the values in the "yoked" vehicle group at
      asymptotically equal to 9h; 3) a further decline below control levels, reaching a
      nadir at asymptotically equal to 24h; 4) in the 48h session, a second phase of
      increased DA oxidation currents accompanied the reinstatement of a second bout of
      d-amphetamine self-administration, which followed an abstinence period.
      Examination of chronoamperometric records for individual rats, before, during and
      after the abstinence periods revealed 1) a significant reduction in basal DA
      oxidation currents in the self-administration group, relative to both "yoked"
      groups; 2) resumption of self-administration when DA currents were still
      attenuated; 3) an increase in DA currents following reinitiation of d-amphetamine
      self-administration. Comparison of changes in DA oxidation currents between
      groups revealed 1) significantly greater increases with self-administration vs
      "yoked" d-amphetamine administration; 2) a significant decrease in the self
      administration vs the "yoked" d-amphetamine group during abstinence and 3) a
      circadian variation in the "yoked" vehicle group that was out of phase with the
      groups receiving the drug.

PMID- 11224468
TI  - Schedule-induced polydipsic choice between cocaine and lidocaine solutions:
      critical importance of associative history.
AB  - Two groups of rats given daily, 3-h, intermittent food-pellet sessions, which
      induced polydipsia, drank either cocaine (COC) or lidocaine (LIDO) solutions.
      Then water was made available concurrently, but neither group preferred drug
      solution. When drug was presented in a glucose-saccharin vehicle, which was
      subsequently faded out, both the COC and LIDO groups acquired a strong preference
      for drug solution rather than water. Half of each group was continued, and half
      was directly faded to a preference for the other drug solution rather than water.
      Then COC and LIDO solutions were available concurrently and animals
      overwhelmingly preferred the drug solution that historically had been associated
      with the glucose-saccharin vehicle. Finally, the COC-preferring and LIDO
      preferring groups had the concentrations of their preferred drug increased step
      wise several times and preferences were maintained. Thus, acquired drug
      preferences remained stable as preferred drug concentration was increased, making
      it more bitter than the nonpreferred drug. The abuse potential of COC affords it
      little advantage over LIDO in the institution and maintenance of oral drug
      preference, suggesting that the post-ingestive pharmacological action of a drug
      is less important for acquiring drug-taking than is a history of associating the
      drug with another reinforcing event.

PMID- 11224469
TI  - Utilization of a novel model of food reinforced behavior involving neuropeptide
      Y, insulin, 2-deoxy-d-glucose and naloxone.
AB  - The cyclic-ratio schedule methodology exposes animals to an ascending followed by
      a descending sequence of ratio values over six consecutive cycles. The response
      functions, obtained by plotting response rates against reinforcement rates at
      each schedule value, are argued to provide features useful in the evaluation of
      drug effects on feeding behavior. In the present study the effects of s.c.
      insulin (5.0IU/kg), i.c.v. neuropeptide Y (NPY) (5.0ug/5.0ul), i.c.v. insulin
      (0.5mU/5.0ul), i.c.v. 2-deoxyglucose (2-DG) (10.0ug/5.0ul), i.c.v. naloxone (NLX)
      (50.0ug/5.0ul) in conjunction with i.c.v. NPY (5.0ug/5.0ul), and i.c.v. NLX alone
      (50.0ug/5.0ul) were assessed, i.c.v. NPY, insulin and 2-DG caused an elevation of
      the response function obtained by plotting response rates against reinforcement
      rates but did not affect the slope of the function. This elevation was similar to
      that observed after increasing the incentive value of the reinforcer (i.e.,
      similar to increasing a 5.0% sucrose concentration reinforcer to 10.0%, and to
      substituting 45mg sweet food pellets for 45mg grain pellets). S.c. insulin
      produced no shift in the function from baseline, and i.c.v. NLX blocked the
      effect of i.c.v. NPY. I.c.v. NLX given alone reduced the slope of the response
      function, by selectively reducing response rates at the higher schedule values, a
      shift in the function similar to that observed following an increase in body
      weight. Since the literature on NPY and insulin would suggest that their effects
      are mediated through mechanisms associated with internal regulation, these
      findings were not predicted.

PMID- 11224470
TI  - Conditioned cued recovery of responding following prolonged withdrawal from self
      administered cocaine in rats: an animal model of relapse.
AB  - The present study investigated the ability of drug-associated cues to reinstate
      extinguished responding following an extended period of withdrawal from cocaine
      self-administration. Rats self-administered cocaine (0.33mg/infusion) for 2 weeks
      of daily 3-h limited-access sessions under a fixed-interval (FI) schedule of
      reinforcement, in which responding resulted in simultaneous illumination of a
      stimulus light and drug infusions. Rats were then exposed to 20 daily extinction
      sessions. Noncontingent presentation of the stimulus light and infusion pump
      sound on day 21 of extinction resulted in a significant increase in responding.
      Twenty days later (43 days after cocaine withdrawal), rats returned to the
      operant chamber and exposed to drug-associated cues responded significantly more
      than animals exposed to extinction conditions. In a second experiment, using a
      form of variable-interval schedule in which the stimulus light was presented
      prior to drug infusions, stimulus-cued recovery of responding was similar to that
      obtained under the FI schedule. A third experiment showed that noncontingent
      presentation of the stimulus light alone on day 21 failed to reinstate
      extinguished responding, suggesting that stimulus-cued reinstatement of
      responding was due to a compound stimulus or preferential conditioning of the
      infusion pump sound. The present paradigm may serve as a useful model for the
      investigation of drug abuse and relapse, since it allows for the independent
      examination of the reinforcing and conditioned effects of a drug.

PMID- 11224471
TI  - Sex differences in discriminative stimulus effects of morphine in the rat.
AB  - Nine female and ten male rats were trained to discriminate 3.0mg/kg s.c. morphine
      from saline. The six female rats that acquired and maintained the morphine
      discrimination did so in significantly fewer sessions than the eight males did
      (28 +/- 5 vs 51 +/- 9 sessions, respectively), and the ED(50) for morphine
      substitution was significantly lower in females (0.69 +/- 0.15 vs 1.28 +/-
      0.20mg/kg). The time course of morphine substitution was approximately equivalent
      in females and males. The u agonist fentanyl completely substituted for morphine
      in both sexes, with no sex difference in potency to substitute for morphine. The
      u agonist buprenorphine partially or completely substituted for morphine in all
      females and five of six males, but at a lower dose in females (ED(50) 0.009 +/-
      0.002 vs 0.019 +/- 0.006mg/kg). The delta agonist BW373U86 partially substituted
      for morphine in both sexes, with no potency differences; the kappa agonist
      U69,593 and the non-opioid cocaine did not substitute for morphine in either sex.
      On a test of spontaneous locomotor activity, morphine increased locomotion to a
      slightly but not significantly greater extent in males than in females. Morphine
      also produced significantly greater hotplate antinociception in males than in
      females. Further drug discrimination training with a lower dose of morphine,
      1.0mg/kg, decreased the ED(50) for morphine substitution in females and males to
      0.26 +/- 0.06 vs 0.45 +/- 0.11mg/kg, respectively (not significant). In a
      separate group of age-matched rats, there was no sex difference in brain or
      plasma levels of morphine measured via HPLC 20min post-injection, the
      pretreatment time used to examine behavioral effects of morphine. The HPLC
      results, plus the fact that sex differences were not the same for all behavioral
      effects of morphine, suggest that sex differences in discriminative stimulus
      effects of morphine are not due to differential pharmacokinetics. The possibility
      that sex differences in morphine discrimination reflect sex differences in opioid
      receptor pharmacology, or differential reinforcement between morphine and saline
      levers for males but not females, is discussed.

PMID- 11224472
TI  - The effects of opioid receptor antagonism on the discriminative stimulus effects
      of cocaine and d-amphetamine in the rat.
AB  - There is evidence that suggests that endogenous opioids can modulate brain
      dopamine systems and the behavioral effects of drugs that are mediated by those
      systems. The aim of this study was to examine the role of endogenous opioids in
      the discriminative stimulus effects of d-amphetamine and cocaine, through the use
      of receptor antagonists. Two separate groups of rats were trained to discriminate
      1.0mg/kg d-amphetamine or 10mg/kg cocaine from saline, in a discrete-trial,
      avoidance/escape procedure. Dose-response curves for d-amphetamine (0.1-1.0mg/kg,
      i.p.) and cocaine (1.0-10mg/kg, i.p.) were generated (using a cumulative dosing
      regimen) in the absence and presence of: the nonselective opioid antagonist
      naloxone (1.0 and 5.0mg/kg, s.c.), the delta-opioid antagonist naltrindole (10
      and 30ug, i.c.; 1mg/kg, i.p.), the mu-opioid antagonist beta-funaltrexamine
      (30ug, i.c.), and the kappa-opioid antagonist nor-binaltorphimine (norBNI) (10
      and 30ug, i.c.). The ED(50)s for d-amphetamine and cocaine alone were 0.2mg/kg
      (0.16-0.33) and 3.9mg/kg (2.7-5.1), respectively. None of the opioid antagonists
      produced significant changes in the ED(50) for d-amphetamine. NorBNI
      significantly increased the potency of cocaine to produce a discriminative
      stimulus (ED(50) 2.2mg/kg; 1.7-2.6), whereas the other antagonists were without
      effect. Endogenous mu- and delta-opioids do not appear to be involved in
      mediating the discriminative stimulus effects of d-amphetamine or cocaine;
      however, the endogenous kappa-opioids might have a negative modulatory effect on
      cocaine's interoceptive cue. The lack of effect of norBNI on the discriminative
      stimulus effects of d-amphetamine suggests novel differences in the mechanisms of
      action of d-amphetamine and cocaine.

PMID- 11224473
TI  - 5-HT(1A) receptors play an important role in modulation of behavior of rats in a
      two-compartment black and white box.
AB  - The involvement of serotonergic receptor subtypes in modulation of rat behavior
      in a black and white test box was studied. The high efficacy 5-HT(1A) receptor
      agonist 8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetraline] was inactive, and the
      partial agonist buspirone showed an anxiolytic-like response that was weaker than
      the response to diazepam. The non-selective 5-HT(1) receptor agonists TFMPP [1
      (trifluoromethylphenyl) piperazine] and eltoprazine were inactive. Low doses of
      the 5-HT(1A) receptor antagonist WAY 100.635 [N-[2-[4-(2-methoxyphenyl)-1
      piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide] induced an anxiolytic
      like response; 10-100 times higher doses induced an anxiogenic-like response. The
      5-HT(2A/2C) and 5-HT(3) receptor antagonists ritanserin and ondansetron induced
      anxiolytic-like responses. The 5-HT(2A/2C) receptor agonist DOI [1-(2,5-dimethoxy
      4-iodophenyl)-2-aminopropane] and the 5-HT(2A) receptor antagonist-MDL 100.151
      [(=) chi-(2,3-dimethoxyphenyl)-1-[2-(4-fluorphenyl)ethyl]-4-piperidin-methanol]
      were inactive. 8-OH-DPAT potentiated the anxiolytic-like effect of ritanserin. It
      is suggested that 5-HT(1A) and 5-HT(2C) receptors are involved in mediation of
      exploratory behavior in rats, and that the 5-HT receptor subtype mediated effects
      may modulate one another.

PMID- 11224474
TI  - Interaction between mu and kappa receptors located in the parabrachial area in
      the opioid control of preference threshold for saccharin: modulatory role of
      lateral hypothalamic neurones.
AB  - In the course of our previous analyses of gustatory reward processes, we showed
      that, in normal or sham-lesioned rats, the preference threshold for saccharin
      over water was observed with a 0.3mM solution of the sweetener. The same solution
      was neutral for rats whose lateral hypothalamic neurones had been destroyed by
      ibotenic acid. Furthermore, injection of small dose of morphine (50ng) in the
      second gustatory relay-station, the parabrachial area, suppressed preference for
      the 0.3mM saccharin solution in sham-lesioned rats, while the same injection
      induced preference in lesioned rats. The aim of the present study was to
      determine if this paradoxical effect of morphine, in particular the suppressive
      action observed in sham-lesioned rats, could be explained by a differential
      activation of u and kappa receptors located in the parabrachial area. Using the
      choice test between 0.3mM solution of saccharin and water, we compared the effect
      of intra-parabrachial injection of 50ng of morphine to those obtained with the u
      agonist DAGO, the putative endogenous kappa ligand, dynorphin A(1-13) (Dyn A(1
      13)) and the kappa antagonist, nor-binaltorphimine (nor-BNI). Increasing doses of
      each agonist and the antagonist were tested in independent groups of rats
      including lesioned and sham-lesioned animals. The same doses of DAGO that
      increased preference in sham-lesioned animals, decreased saccharin and water
      intakes in lesioned rats. On the contrary, Dyn A(1-13) dose-dependently decreased
      preference in the control rats and increased preference in lesioned animals. The
      effects of increasing doses of nor-BNI were more variable. To clarify the
      respective roles of the u and kappa receptors, we tested the effect of two
      mixtures: (1) the simultaneous injection of DAGO and Dyn A(1-13) at doses
      ineffective when tested separately reproduced the paradoxical effect of morphine
      in each group of rats; (2) morphine effects were reversed when kappa receptors
      were blocked by a prior injection of nor-BNI. Taken together, the results suggest
      that: (1) in the parabrachial area of the normal rat, two opioidergic components,
      behaving antagonistically to each other, are implicated in the control of
      gustatory preference, a u component with rewarding properties and a kappa
      component with aversive properties; (2) the main effect of the lateral
      hypothalamic lesion is to invert the properties of these two components; and (3)
      at least in the parabrachial area, u and kappa receptors are functionally coupled
      and must be co-activated to reproduce the full effect of morphine.

PMID- 11224475
TI  - Different behavioural profiles of the R(+)- and S(-)-enantiomers of 8-hydroxy-2
      (di-n-propylamino) tetralin in the murine elevated plus-maze.
AB  - (=) 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) has been the most widely
      used pharmacological tool in research on 5-HT(1A) receptor function. In the
      present study, the behavioural effects of 8-OH-DPAT entantiomers were compared
      using an ethological version of the murine elevated plus-maze test. Subcutaneous
      pretreatment (-20min) with R(+)-8-OH-DPAT (0.03-1.0mg/kg) produced a pronounced;
      and dose-dependent behavioural suppression (decreased open/closed/total arm
      entries and increased nonexploratory behaviours). In contrast, over the same dose
      range, S(-)-8-OH-DPAT reduced several ethological indices of anxiety without
      altering the majority of conventional parameters or general activity levels, e.g.
      arm entries and per cent time measures, as well as head dipping. Findings are
      discussed in relation to differences in the intrinsic activity of 8-OH-DPAT
      isomers at 5-HT(1A) sites and the putative role of these receptors in anxiety
      related processes. The differential behavioural profiles of 8-OH-DPAT enantiomers
      suggest that racemic 8-OH-DPAT may not be an ideal tool for research on the
      behavioural pharmacology of 5-HT(1A) receptors.

PMID- 11224476
TI  - Antagonism of amphetamine-induced disruption of latent inhibition by the atypical
      antipsychotic olanzapine in rats.
AB  - The present study aimed at characterising the effects of the new antipsychotic
      olanzapine in a Latent Inhibition (LI) paradigm. A conditioned emotional response
      (CER) procedure was used, consisting of three stages: pre-exposure, in which the
      to-be-conditioned stimulus (a tone) was presented six times without being
      followed by reinforcement; conditioning, in which the pre-exposed stimulus was
      paired twice with reinforcement (a foot shock); and test, in which LI was
      assessed by the suppression of licking during the tone presentation. In
      Experiment I, it was found that pre-treatment with an intermediate dose
      (0.312mg/kg) of olanzapine, but not with lower (0.003; 0.031mg/kg) or higher
      doses (0.625; 1.25mg/kg), restored LI in amphetamine-treated (1.5mg/kg) animals.
      This effect could not be attributed to a disruptive effect of olanzapine on CER
      learning, as olanzapine per se had no effect on this conditioning (Experiment 2).
      In Experiment 3, olanzapine did not antagonise the amphetamine-induced locomotor
      hyperactivity. As olanzapine has not only dopaminergic, but also serotonergic,
      adrenergic, histaminergic and cholinergic activities, the differential effects of
      olanzapine on amphetamine-induced disruption of LI and hyperactivity may reflect
      an action on several pharmacological targets, possibly interacting with one
      another.

PMID- 11224477
TI  - Septal scopolamine-systemic diazepam interaction in passive avoidance learning in
      rats.
AB  - The role of the septal region in passive avoidance (step-through) learning was
      studied by administering 15ug/0.5ul of scopolamine intraseptally to rats,
      together with an i.p. injection of 2mg/kg of diazepam to the same animals. The
      combined treatment provoked a severe impairment in retention of the learning
      situation, whereas animals which received either scopolamine or diazepam alone
      did not show any deficit.

PMID- 11224478
TI  - Nutritional and socio-economic status in the prognosis of childhood acute
      lymphoblastic leukemia.

PMID- 11224479
TI  - Current understanding of methotrexate pharmacology and efficacy in acute
      leukemias. Use of newer antifolates in clinical trials.
AB  - BACKGROUND AND OBJECTIVES: Methotrexate (MTX) is a key drug in the curative
      regimen of children with acute lymphocytic leukemia. This drug is widely used not
      only in the treatment of neoplastic diseases such as leukemia, lymphoma,
      choriocarcinoma, head and neck cancer and osteogenic sarcoma, but also for
      various autoimmune diseases, e.g., rheumatoid arthritis and psoriasis, and for
      the prevention of graft-versus-host disease after transplantation. The
      development of drug resistance is the limiting factor in the use of MTX. This
      review will outline the mechanisms of acquired and natural resistance to MTX that
      have been studied in patients affected by acute lymphocytic leukemia and acute
      myelocytic leukemia and the cell cycle genes involved in MTX resistance. This
      information may improve the use of MTX or could lead to the development of better
      drugs. Moreover a short description of newer antifolates with their mechanisms of
      action is presented. EVIDENCE AND INFORMATION SOURCES: The authors of this review
      have a long-standing interest in the mechanism of action of and resistance to MTX
      and other antifolates. Information from journal articles covered by the Science
      Citation Index and Medline has been reviewed together with work performed by the
      authors. PERSPECTIVES: Antifolates continue to be an extremely important class of
      drugs for the treatment of non-neoplastic as well as neoplastic diseases. New
      inhibitors that target dihydrofolate reductase as well as other folate-dependent
      enzymes are being evaluated in the clinic, and show promise.

PMID- 11224480
TI  - Detection of recombinant human erythropoietin abuse in athletes utilizing markers
      of altered erythropoiesis.
AB  - BACKGROUND AND OBJECTIVES: The detection of recombinant human erythropoietin (r
      HuEPO) abuse by athletes remains problematic. The main aim of this study was to
      demonstrate that the five indirect markers of altered erythropoiesis identified
      in our earlier work were reliable evidence of current or recently discontinued r
      HuEPO use. A subsidiary aim was to refine weightings of the five markers in the
      initial model using a much larger data set than in the pilot study. A final aim
      was to verify that the hematologic response to r-HuEPO did not differ between
      Caucasian and Asiatic subjects. DESIGN AND METHODS: Recreational athletes
      resident in Sydney, Australia (Sydney, n = 49; 16 women, 33 men) or Beijing,
      China (Beijing, n=24; 12 women, 12 men) were randomly assigned to r-HuEPO or
      placebo groups prior to a 25 day administration phase. Injections of r-HuEPO (or
      saline) were administered double-blind at a dose of 50 IU/kg three times per
      week, with oral iron (105 mg) or placebo supplements taken daily by all subjects.
      Blood profiles were monitored during and for 4 weeks after drug administration
      for hematocrit (Hct), reticulocyte hematocrit (RetHct), percent macrocytes
      (%Macro), serum erythropoietin (EPO) and soluble transferrin receptor (sTfr),
      since we had previously shown that these five variables were indicative of r
      HuEPO use. RESULTS: The changes in Hct, RetHct, %Macro, EPO and sTfr in the
      Sydney trial were qualitatively very similar to the changes noted in our previous
      administration trial involving recreational athletes of similar genetic origin.
      Statistical models developed from Fisher's discriminant analysis were able to
      categorize the user and placebo groups correctly. The same hematologic response
      was demonstrated in Beijing athletes also administered r-HuEPO. INTERPRETATION
      AND CONCLUSIONS: This paper confirms that r-HuEPO administration causes a
      predictable and reproducible hematologic response. These markers are disturbed
      both during and for several weeks following r-HuEPO administration. This work
      establishes an indirect blood test which offers a useful means of detecting and
      deterring r-HuEPO abuse. Ethnicity did not influence the markers identified as
      being able to detect athletes who abuse r-HuEPO.

PMID- 11224481
TI  - Clinical and hematologic features of beta0-thalassemia (frameshift 41/42
      mutation) in Thai patients.
AB  - BACKGROUND AND OBJECTIVES: Frameshift 41/42 mutation is the most common mutation
      of beta0-thalassemia found in Thailand. We studied clinical and hematologic
      features in 84 patients and relatives with frameshift 41/42 to determine whether
      it is possible to predict phenotypic severity from genetic factors. DESIGN AND
      METHODS: The clinical phenotypes and hematologic data of Thai patients with
      frameshift 41/42 were studied. Alpha-thalassemia, Hb Constant Spring (HbCS) genes
      and the presence of Xmnl-Ggamma polymorphism were studied in patients who had
      mild symptoms. RESULTS: Homozygotes for frameshift 41/42 and compound
      heterozygotes for frameshift 41/42 and beta0-thalassemia produced severe symptoms
      and have a thalassemia major phenotype. Combination of frameshift 41/42 and beta0
      thalassemia or Hb E produced mild to moderate symptoms with thalassemia
      intermedia phenotype and severe symptoms with thalassemia major phenotype. The co
      inheritance of beta-thalassemia or HbCS gene or the presence of Xmnl-Ggamma
      polymorphism was not associated with mild disease in patients with frameshift
      41/42 and HbE. INTERPRETATION AND CONCLUSIONS: The clinical phenotype of
      homozygotes for frameshift 41/42 and compound heterozygotes for frameshift 41/42
      and beta0-thalassemia could be used to predict a severe phenotype with
      thalassemia major. However, the clinical phenotype of compound heterozygotes of
      frameshift 41/42 and beta0-thalassemia or Hb E were variable and could not be
      accurately predicted. Associations between concomitant alpha-thalassemia or HbCS
      of the presence of Xmnl-Ggamma polymorphism and a mild clinical phenotype are not
      apparent, indicating the involvement of other ameliorating determinants or
      genetic modifications.

PMID- 11224482
TI  - Rearrangements of the beta-globin gene cluster in apparently typical betaS
      haplotypes.
AB  - BACKGROUND AND OBJECTIVES: The majority of the chromosomes with the betaS gene
      have one of the five common haplotypes, designated as Benin, Bantu, Senegal,
      Cameroon, and Arab-Indian haplotypes. However, 5-10% of the chromosomes have less
      common haplotypes, usually referred to as atypical haplotypes. We have
      demonstrated that most atypical haplotypes are generated by recombinations. The
      present study was carried out in order to explore whether recombination also
      occurs in chromosomes with the common (or typical) haplotypes. DESIGN AND
      METHODS: We screened the HS-2 region of the beta-globin gene locus control region
      (LCR) in 244 sickle cell patients who had typical restriction fragment length
      polymorphism (RFLP)-defined haplotypes of the betaS-gene cluster. For 14 cases in
      which the expected and the observed LCR repeat-sequence sizes were discrepant,
      the analysis was extended to other unexplored polymorphic markers of the bS
      globin gene cluster, i.e.: pre-Ggamma framework, pre-Ggamma 6-bp deletion, HS-2
      LCR (AT)xR(AT)y and pre-beta(AT)xTy repeats, and the intragenic beta-globin gene
      framework. RESULTS: In all 14 cases (15 chromosomes) in which the LCR repeat
      sequence sizes were discrepant, a recombination involving a typical 3' segment of
      the betaS globin gene cluster was demonstrated. In most of the cases, the
      recombination site was located between the beta-globin gene and the betaLCR. Nine
      cases involving recombination were detected among 156 Brazilian HbS homozygotes
      and five among 88 African patients homozygotes for the Benin haplotype.
      INTERPRETATION AND CONCLUSIONS. Thus, 3.1% of apparently typical haplotypes
      linked to the sickle cell gene involve recombinations similar to those that
      generate the atypical haplotypes, a finding that reinforces the picture of the
      beta-globin gene cluster as highly dynamic.

PMID- 11224483
TI  - Cellular prion protein is expressed on peripheral blood mononuclear cells but not
      platelets of normal and scrapie-infected sheep.
AB  - BACKGROUND AND OBJECTIVES: Transmissible spongiform encephalopathies (TSEs)
      including sheep scrapie are characterized by the conversion of a normal, cellular
      prion protein (PrPc) to an abnormal protease-resistant form (PrPSc). Like human
      peripheral blood, the peripheral blood of scrapie-infected sheep remains one
      possible source of disease transmission. As a first step in understanding the
      disease requirements in the natural scrapie host, the presence of PrPc was
      evaluated in peripheral blood cells from five normal and five scrapie-infected
      Suffolk sheep. DESIGN AND METHODS: Live peripheral blood cells from normal and
      scrapie-infected sheep were analyzed for the presence of PrP using flow cytometry
      and reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: PrP mRNA
      was detected in peripheral blood mononuclear cells (PBMC) but not in platelets or
      granulocytes. Consistent with PrP mRNA expression, cell-surface expressed PrP was
      detected on PBMC, but was not detected on granulocytes, platelets, or
      erythrocytes. Two-color flow cytometric analysis of PBMC specific phenotypes
      revealed that regardless of scrapie-status, expression of PrP was significantly
      higher on B2 positive B-lymphocytes than on CD4, CD8, WC1 positive T-lymphocytes
      or CD14 positive monocytes. In addition, PrP expressed on PBMC from normal and
      scrapie-infected sheep was sensitive to proteinase K (PK)and phosphatidylinositol
      specific phospholipase C (PIPLC). INTERPRETATION AND CONCLUSIONS: Regardless of
      the scrapie-status of the sheep, resting PBMC transcribe PrPc and express PrPc as
      a cell-surface protein sensitive to both PK and PIPLC. Because of the abundance
      of PrPc on PBMC, future diagnostic tests using PK and PIPLC to discriminate
      between protease sensitive and resistant PrP must be carefully evaluated.

PMID- 11224484
TI  - Impact of CD133 (AC133) and CD90 expression analysis for acute leukemia
      immunophenotyping.
AB  - BACKGROUND AND OBJECTIVES: AC133 is a novel monoclonal antibody (Moab) reacting
      with a population of immature/primitive or granulo-monocytic committed CD34+ve
      cells. Up to now, only few studies with small numbers of cases have examined
      AC133 (recently designated CD133) expression in acute leukemia. To determine the
      value of this Moab for acute leukemia immunophenotyping, we investigated a large
      series of leukemic cell samples for their reactivity with Moab AC133. DESIGN AND
      METHODS. A total of 298 cell samples from patients with de novo acute myeloid
      leukemia (AML) (n=142), acute lymphoblastic leukemia (ALL) (n=119), CD34+ve
      biphenotypic acute leukemia (n=13), and CD34+ve CML blast crisis (=BC; 21 myeloid
      BC/3 lymphoid BC) were investigated by flow cytometry for Moab AC133
      reactivity.CD133 expression was compared with CD90(Thy-1) expression, another
      CD34-associated antigen. RESULTS: Fifteen (5%) samples expressed CD90, whereas
      114 (38%) samples were positive for Moab AC133 (20% cut-off level). No
      significant differences in CD133 and CD90 expression levels between AML and ALL
      were observed. In AML, but not ALL, CD133 was more often expressed in CD34+ve
      cases than in CD34-ve ones (p<0.00001). However, CD133 expression was not
      restricted to CD34+ve leukemic cells in individual cell samples. All 8 pro-B-ALL
      cell samples with 11q23-anomalies and MLL (mixed lineage leukemia) gene
      translocations were positive for CD133, whereas only 2 of 9 pro-B-ALL without MLL
      gene translocations expressed CD133 (p<0.002). In contrast, none of the 5 AML
      cell samples with a t(9;11) and MLL gene translocation reacted with Moab AC133.
      CD34+ve CML cells in myeloid BC were less often positive for CD133 than CD34+ve
      de novo AML cells (p<0.0001). INTERPRETATION AND CONCLUSIONS: CD133 and CD90
      expression analysis is not helpful for lineage determination in acute leukemia
      immunophenotyping. However, MoabAC133 may be an informative marker for the
      detection and further characterization of immature AML cells, as well as pro-B
      ALL cells with MLL gene translocations, by flow cytometry.

PMID- 11224485
TI  - Molecular characterization of acute myeloblastic leukemia according to the new
      WHO classification: a different distribution in Central-West Spain.
AB  - BACKGROUND AND OBJECTIVES: Molecular analysis has contributed to the
      identification of several non-random chromosomal translocations, such as
      t(15;17), t(8:21), inv(16)/t(16;16) and 11q23 abnormalities, typically associated
      with acute myeloid leukemia (AML). The identification of these chromosomal
      abnormalities helps not only to define different AML subtypes with distinct
      prognoses and treatments but also to monitor the disappearance of malignant cells
      after treatment. Recent reports suggest that the frequency of these alterations
      may differ according to geographic distribution. However, most of these reports
      focus on just one or two genetic alterations, which may lead to some selection
      bias. Appropriate epidemiological studies should be based on unselected
      consecutive series of patients in which all relevant genes are simultaneously
      analyzed. The aim of the present study was to explore whether or not the
      incidence of genetic lesions in Spanish AML patients differs from that reported
      in other countries. DESIGN AND METHODS: In a series of 145 consecutive un
      selected adult patients with AML we simultaneously analyzed the presence of 4
      genetic abnormalities, PML/RARalpha for t(15;17), AML1/ETO for t(8;21),
      CBFbeta/MYH11 for inv(16)/t(16;16) and rearrangements of the MLL gene for 11q23
      abnormalities. AML were classified using the new World Health Organization (WHO)
      classification for hematologic malignancies. The techniques used were
      standardized according to the recommendations of the European BIOMED-1 Concerted
      Action. RESULTS: The PML/RARalpha transcript was present in 34 patients (23.4%)
      (23 were bcr1, 2 bcr2 and 9 bcr3). The AML1/ETO fusion transcript was detected in
      only 2 cases (1.4%) both with M2 morphology, but 29 other cases with M2
      morphology were negative. CBFbeta/MYH11 transcript was present in 9 cases (6.2%)
      eight of them displaying M4Eo morphology. Finally, 5 cases (3.5%) showed
      rearrangements of theMLL gene. Our results differ from those reported from the
      United States and North/Central Europe, particularly regarding the incidence of
      t(15;17) and t(8;21) translocations. In Spain the frequency of t(15;17) is higher
      while that of t(8;21) is lower. INTERPRETATION AND CONCLUSIONS: These data add
      epidemiological information about geographic heterogeneity of such chromosome
      aberrations in AML and would contribute to the design of specific screening
      strategies adapted to the incidence in each country.

PMID- 11224486
TI  - Competitive polymerase chain reaction as a method to detect the amplification of
      bcr-abl gene of chronic myeloid leukemia.
AB  - BACKGROUND AND OBJECTIVES: The chimeric product of the bcr-abl rearranged gene is
      critical in the pathogenesis of chronic myeloid leukemia (CML), yet its role in
      the progression of the disease remains unclear. There is some evidence that
      increased bcr-abl expression levels, possibly due to gene amplification, precede
      the clonal evolution of CML hematopoietic progenitors toward a fully transformed
      phenotype and might be involved in their resistance to interferon-alpha or
      tyrosine kinase inhibitors. DESIGN AND METHODS: To quantify the bcr-abl gene both
      at the genomic and at the transcriptional levels we developed a competitive
      polymerase chain reaction (PCR) strategy. The competitive PCR technique is based
      upon the co-amplification of the sample template (target) together with
      increasing amounts of a DNA fragment (competitor) sharing with the target the
      primer recognition sites, but differing in size. We constructed a competitor for
      the quantification of both b2a2 and b3a2 alternative splicing forms of the bcr
      abl chimera and established the accuracy and reproducibility of our competitive
      strategy in a clone of the murine 32DG hematopoietic cell line (32D LG7), which
      bears a stable integration of a single copy of p210 bcr-abl fusion gene. We
      utilized this technique to follow, over a period of 200 days, the fusion gene
      copy numbers and transcription rates in several p210 bcr-abl-transduced 32D cell
      clones, an experimental condition mimicking the evolution of CML myeloid
      progenitors in vivo. RESULTS: Our results are consistent with p210 bcr-abl
      overexpression but not gene amplification associated with their clonal evolution.
      Increased p210 bcr-abl transcription rate is associated with the abrogation of
      radiation-induced apoptotic cell death, suggesting a role for the chimeric gene
      expression level in cell life expectancy after a genotoxic insult. INTERPRETATION
      AND CONCLUSIONS: We conclude that the assessment of gene amplification and
      expression might serve to improve prognostic classification and follow-up of CML
      patients.

PMID- 11224487
TI  - Sequential fluorescence in situ hybridization analyses for trisomy 12 in chronic
      leukemic B-cell disorders.
AB  - BACKGROUND AND OBJECTIVES: Trisomy 12 is one of the most common chromosomal
      abnormalities in B-cell chronic lymphocytic leukemia (CLL). The aberration is
      readily detected by fluorescence in situ hybridization (FISH). There are only a
      few reports in which FISH analyses have been used to study the expansion of the
      trisomy 12 clone over time. DESIGN AND METHODS: Repeat FISH analyses were
      performed in 77 patients with a chronic leukemic B-cell disorder. The aim was to
      study the development of the trisomy 12 clone throughout the course of the
      disease, to measure the effect of therapy on the proportion of trisomic cells,
      and to relate the findings to the response to therapy. RESULTS: Fifty-eight of
      the 60 patients with no trisomy 12 at the initial test were consistently disomic
      for chromosome 12, while 2 patients seemingly acquired trisomy 12 during follow
      up. Seventeen patients showed trisomy 12 at the first test. Expansion of the
      trisomy 12 clone was seen in all patients with a progressive lymphocytosis. In
      contrast to poor responders, patients responding well to chemotherapy showed a
      significant decrease in the proportion of CD19+ cells with trisomy 12. The effect
      of purine analogs in patients with trisomy 12 seemed inferior, both clinically
      and when studying the effect on the trisomic clone. INTERPRETATIONS AND
      CONCLUSIONS: There is a strong association between expansion of the trisomy 12
      clone and progressive disease, both in treated and untreated patients.
      Conversely, reduction of the trisomic B-cell clone was linked to clinical
      response to chemotherapy. Acquisition of trisomy 12 remains a rare event.

PMID- 11224488
TI  - Microsatellite instability analysis in typical and progressed mantle cell
      lymphoma and B-cell chronic lymphocytic leukemia.
AB  - BACKGROUND AND OBJECTIVES: Microsatellite instability (MSI) is characterized by
      tumor-associated alterations in the germline size of microsatellite repeats
      caused by a reduced efficacy of the DNA mismatch repair machinery. The aim of
      this study was to investigate the presence of MSI in a number of cases of
      indolent and aggressive mantle cell lymphoma (MCL) and B-cell chronic lymphocytic
      leukemia (B-CLL) to determine its possible role in the initial development and
      progression of these disorders. DESIGN AND METHODS: We examined the presence of
      MSI in 28 B-CLL, 24 typical and 4 transformed B-CLL (Richter's syndrome) and 29
      MCL, 19 typical and 10 blastoid variants by using a panel of 10 microsatellite
      markers and analyzed them using an AbiPrism 310 DNA sequencer. Fisher's exact
      test was used to compare categorical variables and Mann-Whitney's U-test for
      continuous variables. RESULTS: MSI alterations were not observed in any case of
      MCL or Richter's syndrome and in only three (13%) patients with typical B-CLL.
      Two of these patients also had loss of heterozygosity in one of the 10 sites
      examined. These patients presented with a more advanced stage, diffuse bone
      marrow involvement, and poorer performance status than patients without these
      alterations. INTERPRETATION AND CONCLUSIONS: These findings indicate that MSI is
      not involved in the pathogenesis or progression of B-CLL and MCL but may appear
      in a small subset of patients with advanced B-CLL.

PMID- 11224489
TI  - Primary mediastinal large B-cell lymphoma with sclerosis: a clinical study of 89
      patients treated with MACOP-B chemotherapy and radiation therapy.
AB  - BACKGROUND AND OBJECTIVES: Primary mediastinal large B-cell lymphoma (PMLBCL)
      with sclerosis has recently been recognized as a specific clinical and pathologic
      entity for which the best therapeutic approach seems to be a combination of
      chemotherapy and radiotherapy. DESIGN AND METHODS: Between 1989 and 1998, 89
      previously untreated patients with PMLBCL with sclerosis were treated with a
      combination of a third-generation chemotherapy regimen (MACOP-B) and mediastinal
      radiation therapy. The response evaluations were examined after chemotherapy and
      at the end of radiotherapy. RESULTS: Twenty-three (26%) patients achieved a
      complete response (CR) and 59 (66%) obtained a partial response (PR) after the
      MACOP-B regimen. After radiation therapy, 55/59 (93%) of the patients in PR
      achieved CR. The CR rate at the end of the treatment was 88% (78/89). Only 7 (8%)
      patients were non-responders. Among the 78 patients who obtained a CR there were
      7 (9%) relapses in a median follow-up of 5 months (all relapses occurred within 9
      months); the other 71 patients are currently in continuous CR with a median
      follow-upof 45 months (range, 4-110 months). Projected overall survival was 86%
      at 9 years; the relapse-free survival curve of the 78 patients who achieved CR
      was 91% at 9 years. INTERPRETATION AND CONCLUSIONS: In patients with PMLBCL with
      sclerosis, combined modality treatment using the MACOP-B chemotherapy regimen and
      radiation therapy induces a good remission rate with the patients having a
      greater than 90% chance of surviving disease-free at 9 years. Radiotherapy often
      plays a pivotal role in obtaining CR status.

PMID- 11224491
TI  - The effect of the interleukin-6 c/g-174 polymorphism and circulating interleukin
      6 on fibrinogen plasma levels.
AB  - BACKGROUND AND OBJECTIVES: C-reactive protein (C-RP) levels correlate with
      fibrinogen values and are predictive of coronary artery disease. Interleukin-6
      (IL-6) strongly regulates the production of C-RP. A polymorphism (C/G-174) within
      the IL-6 gene has been shown to affect IL-6 gene expression and plasma
      concentrations. DESIGN AND METHODS: In 598 asymptomatic employees of a hospital
      in Southern Italy, we investigated the association between IL-6 C/G-174 gene
      variants and plasma fibrinogen levels. RESULTS: Subjects with IL-6 plasma levels
      >2.0 pg/mL had a higher body mass index (BMI) (24.5+/-1.2) than subjects with IL
      6 levels below this cut-off value (23.7+/-1.2; p =0.005). No association was
      found with sex, cigarette smoking, or alcohol consumption (p always>0.05). When
      the whole sample was analyzed according to the IL-6 C/G-174 polymorphism, there
      was no difference with respect to age, sex, alcohol consumption, cigarette
      smoking, total cholesterol, triglycerides, and body mass index. Median plasma
      fibrinogen levels, as well as carriers of plasma levels of IL-6 >2.0 pg/mL and C
      RP >0.33 mg/L, were similar among subjects with different IL-6 genotypes.
      Similarly, no difference was observed when only carriers of plasma levels of IL-6
      >2.0 pg/mL were analyzed, whereas in those with C-RP >0.33 mg/L IL-6 GG carriers
      had significantly lower plasma fibrinogen levels. INTERPRETATION AND CONCLUSIONS:
      The investigation of the IL-6 C/G-174 polymorphism does not seem to be a useful
      tool for predicting raised plasma fibrinogen levels.

PMID- 11224490
TI  - In vitro measurement of platelet glycoprotein IIb/IIIa receptor blockade by
      abciximab: interindividual variation and increased platelet secretion.
AB  - BACKGROUND AND OBJECTIVES: Inhibition of soluble fibrinogen binding to activated
      platelets represents the target of pharmacologic approach with antagonists of the
      glycoprotein IIb/IIIa (GPIIb/IIIa) complex. In this study we assessed the effects
      of abciximab, a recombinant chimeric Fab fraction of the antibody against
      GPIIb/IIIa, on several markers of platelet activation. DESIGN AND METHODS: The
      platelet surface expression of GPIIb/IIIa was measured by a flow cytometry
      technique using a two-color assay. GPIIb/IIIa was detected by FITC-conjugated
      antibodies in whole blood, either unstimulated or exposed to platelet stimuli.
      The following antibodies were used: CD41, which recognizes the IIb/IIIa complex
      both in activated and non-activated conformers, and PAC-1, which is directed
      toward the activated conformer of GPIIb/IIIa. In addition, the same blood sample
      was incubated with CD62 antibody to measure P-selectin, as a marker of a-granule
      degranulation. The effect of abciximab was also assessed by experiments carried
      out on shear stress-induced platelet aggregation, a test that appears to be a
      predictor of platelet hemostatic function. RESULTS: Abciximab inhibited CD41
      binding to glycoprotein IIb (GPIIb) in a concentration-dependent manner and also
      inhibited the binding of PAC-1 to active GPIIb/IIIa. In contrast, membrane
      associated P-selectin was significantly increased by the drug, which suggests
      that blockade of GPIIb/IIIa receptors results in an increased platelet
      degranulation in response to agonists. Shear stress-induced platelet aggregation
      was inhibited by abciximab, with a more pronounced effect on blood filtration,
      which represents an index of platelet aggregate formation. INTERPRETATION AND
      CONCLUSIONS: Our results indicate that GPIIb/IIIa blockade by abciximab is
      accompanied by an increase of a-granule secretion, suggesting that different
      mechanisms regulate these aspects of platelet activation. The described flow
      cytometry technique, that allows the simultaneous in vitro detection of several
      platelet markers, is a suitable method for assessing the effects of agents which
      interfere with platelet function.

PMID- 11224492
TI  - Reference range of complete blood count in blood donors.

PMID- 11224493
TI  - The differential diagnostic values of serum transferrin receptor, serum ferritin
      and related parameters in the patients with various causes of anemia.

PMID- 11224494
TI  - Role of exchange transfusion in patients with severe Falciparum malaria: report
      of six cases.

PMID- 11224495
TI  - Electronic counter-related pseudoleukopenia: more than a rare occurrence.

PMID- 11224496
TI  - AML1/MTG16 fusion gene from a t(16;21)(q24;q22) translocation in treatment
      induced leukemia after breast cancer.

PMID- 11224498
TI  - An unusual acute myeloid leukemia associated with hyper IgE: another case of AML
      M5c?

PMID- 11224497
TI  - Masked inv(3)(q21q26) in a patient with minimally differentiated acute myeloid
      leukemia.

PMID- 11224499
TI  - T-cell lymphoblastic lymphoma associated with the t(6;11)(q27;q23).

PMID- 11224500
TI  - Hermansky-Pudlak syndrome: clinical presentation and confirmation of the value of
      the mepacrine-based cytofluorimetry test in the diagnosis of delta granule
      deficiency.

PMID- 11224501
TI  - Genetic analysis of HLA-typing in Chinese patients with idiopathic
      thrombocytopenic purpura.

PMID- 11224502
TI  - Gastric localization of multiple myeloma.

PMID- 11224503
TI  - Leukemia cutis, chloroma or suspender-induced dermatosis?

PMID- 11224504
TI  - The mobilization with delayed G-CSF administration after standard induction
      chemotherapy and single standard volume apheresis can supply adequate amount of
      CD34(+) cells in patients with breast cancer.

PMID- 11224505
TI  - Acute leukaemia in Jehovah's witnesses.

PMID- 11224506
TI  - Central nervous system involvement in multiple myeloma: a case report.

PMID- 11224507
TI  - Riding technology waves.

PMID- 11224508
TI  - Thyrocytes--not innocent bystanders in autoimmune disease.

PMID- 11224509
TI  - Response to 'Thyrocytes - not innocent bystanders in autoimmune disease'

PMID- 11224510
TI  - Autoimmunity through infection or immunization?

PMID- 11224511
TI  - Notchless T cell maturation?

PMID- 11224512
TI  - Cutting glycolipids down to size.

PMID- 11224513
TI  - The fine line between autoimmune and allergic encephalomyelitis.

PMID- 11224514
TI  - Rac inserts its way into the immune response.

PMID- 11224515
TI  - Les liaisons dangereuses.

PMID- 11224516
TI  - Multifaceted roles of MHC class I and MHC class I-like molecules in T cell
      activation.

PMID- 11224517
TI  - Immunology highlights from the recent literature.

PMID- 11224518
TI  - The expanding B7 superfamily: increasing complexity in costimulatory signals
      regulating T cell function.
AB  - Upon encounter with specific antigen, naiveT helper precursor (THP) cells become
      activated. This event is regulated not only by engagement of the T cell receptor
      (TCR) with peptide presented in the context of major histocompatibility complex
      (MHC) class II molecules but by a number of costimulatory signals. CD28
      engagement by B7-1 and B7-2 on resting THP cells provides a critical signal for
      initial cell cycle progression, interleukin 2 production and clonal expansion.
      However, largely as a consequence of the unraveling of the human genome, it is
      becoming clear that B7-1 and B7-2 are part of a larger family T of related
      counter-receptors that play an essential role in regulating the fate of primed,
      rather then resting,THP cells. These molecules play an important sequential role
      and act, together with B7-1- and B7-2-primed T cells, in the acquisition of
      effector function and/or tolerance induction.

PMID- 11224519
TI  - Molecular basis for Rac2 regulation of phagocyte NADPH oxidase.
AB  - A Rac GTPase-regulated multiprotein NADPH oxidase is critical for the formation
      of reactive oxygen species (ROS) in phagocytic leukocytes and other nonphagocytic
      cells. NADPH oxidase reduces molecular oxygen to form superoxide anion in a two
      step process. Electrons are initially transferred from NADPH to cytochrome b
      associated FAD, then to cytochrome b heme and finally to molecular oxygen. We
      show here that Rac is required for both electron-transfer reactions. Mutational
      and biophysical analysis shows that Rac and p67phox independently regulate
      cytochrome b to catalyze the transfer of electrons from NADPH to FAD. However,
      they must interact with each other to induce the subsequent transfer of electrons
      from FAD to cytochrome b heme and molecular oxygen. This two-step model of
      regulation by Rac GTPase may provide a means of more effectively controlling the
      inflammatory responses of phagocytic leukocytes.

PMID- 11224520
TI  - An unexpected version of horror autotoxicus: anaphylactic shock to a self
      peptide.
AB  - EAE can refer either to experimental autoimmune encephalomyelitis or experimental
      allergic encephalomyelitis. Although EAE is classically a prototypic T helper 1
      (TH1) cell-mediated autoimmune disease, it can also be induced by TH2 cells.
      Characteristically, the most severe manifestation of allergy, anaphylaxis, is
      associated with exposure to a foreign antigen that is often derived from
      medication, insect venom or food. We report here that, after self-tolerance to
      myelin is destroyed, anaphylaxis may be triggered by a self-antigen, in this case
      a myelin peptide. "Horror autotoxicus", which was initially described by Ehrlich,
      may not only include autoimmunity to self, it may also encompass immediate
      hypersensitivity to self, which leads to shock and rapid death.

PMID- 11224521
TI  - Specific missense mutations in NEMO result in hyper-IgM syndrome with
      hypohydrotic ectodermal dysplasia.
AB  - The gene that encodes nuclear factor kappaB (NF-kappaB) essential modulator (or
      NEMO, also known as IKKgamma) is required for activation of the transcription
      factor NF-kappaB. We describe mutations in the putative zinc-finger domain of
      NEMO that result in an X-linked primary immunodeficiency characterized by hyper
      IgM syndrome and hypohydrotic ectodermal dysplasia (XHM-ED). These mutations
      prevent CD40 ligand (CD40L)-mediated degradation of inhibitor of NF-kappaB alpha
      (IkappaB-alpha) and account for the following observations: B cells from XHM-ED
      patients are unable to undergo immunoglobulin class-switch recombination and
      antigen-presenting cells (APCs) are unable to synthesize the NF-kappaB-regulated
      cytokines interleukin 12 (IL-12) or tumor necrosis factor alpha (TNF-alpha) when
      stimulated with CD40L. Nevertheless, innate immunity is preserved in XHM-ED
      patients because APCs retain the capacity to respond to stimulation by
      lipopolysaccharide or Staphylococcus aureus Cowan's antigen (SAC). Overall, the
      phenotype observed in XHM-ED patients shows that the putative zinc-finger domain
      of NEMO has a regulatory function and demonstrates the definite requirement of
      CD40-mediated NF-kappaB activation for B cell immunoglobulin class-switching.

PMID- 11224522
TI  - Efficient T cell activation requires an optimal dwell-time of interaction between
      the TCR and the pMHC complex.
AB  - Cytotoxic T cell (CTL) activation by antigen requires the specific detection of
      peptide-major histocompatibility class I (pMHC) molecules on the target-cell
      surface by the T cell receptor (TCR). We examined the effect of mutations in the
      antigen-binding site of a Kb-restricted TCR on T cell activation, antigen binding
      and dissociation from antigen.These parameters were also examined for variants
      derived from a Kd-restricted peptide that was recognized by a CTL clone. Using
      these two independent systems, we show that T cell activation can be impaired by
      mutations that either decrease or increase the binding half-life of the TCR-pMHC
      interaction. Our data indicate that efficient T cell activation occurs within an
      optimal dwell-time range of TCR-pMHC interaction. This restricted dwell-time
      range is consistent with the exclusion of either extremely low or high affinity T
      cells from the expanded population during immune responses.

PMID- 11224524
TI  - Id3 inhibits B lymphocyte progenitor growth and survival in response to TGF-beta.
AB  - E proteins function in many developmental processes and are essential for the
      formation of lymphocyte progenitors. However, it is not known whether E proteins
      regulate lymphocyte survival, proliferation or differentiation or how their
      activity is regulated during lymphocyte development. We show here a role for Id3,
      an inhibitor of E protein activity, in the induction of apoptosis and growth
      arrest. Id3 is induced in response to transforming growth factor beta (TGF-beta),
      a pleiotropic cytokine that inhibits the growth and survival of normal and
      transformed lymphocyte progenitors. In the absence of Id3, the response of
      lymphocyte progenitors to TGF-beta is perturbed, which indicates that Id3 is a
      mediator of this response. Our data show a key role for E proteins in lymphocyte
      survival and link the activity of E proteins, and their antagonists, to members
      of the TGF-beta family of cytokines.

PMID- 11224523
TI  - Inactivation of Notch 1 in immature thymocytes does not perturb CD4 or CD8T cell
      development.
AB  - Notch proteins influence cell-fate decisions in many developing systems. Several
      gain-of-function studies have suggested a critical role for Notch 1 signaling in
      CD4-CD8 lineage commitment, maturation and survival in the thymus. However, we
      show here that tissue-specific inactivation of the gene encoding Notch 1 in
      immature (CD25+CD44-)T cell precursors does not affect subsequent thymocyte
      development. Neither steady-state numbers nor the rate of production of CD4+ and
      CD8+ mature thymocytes is perturbed in the absence of Notch 1. In addition, Notch
      1-deficient thymocytes are normally sensitive to spontaneous or glucocorticoid
      induced apoptosis. In contrast to earlier reports, these data formally exclude an
      essential role for Notch 1 in CD4-CD8 lineage commitment, maturation or survival.

PMID- 11224525
TI  - Crystal structure of the murine NK cell-activating receptor NKG2D at 1.95 A.
AB  - NKG2D, a homodimeric lectin-like receptor, is a unique stimulatory molecule that
      is found on natural killer cells,T cells and activated macrophages. The natural
      ligands for murine NKG2D are distant major histocompatibility complex homologs,
      retinoic acid early transcript (Rae1) and H-60 minor histocompatibility antigen.
      The crystal structure of the extracellular region of murine NKG2D reveals close
      homology with other C-type lectin receptors such as CD94, Ly49A, rat MBP-A and
      CD69. However, the precise mode of dimeric assembly varies among these natural
      killer receptors, as well as their surface topography and electrostatic
      properties. The NKG2D structure provides the first structural insights into the
      role and ligand specificity of this stimulatory receptor in the innate and
      adaptive immune system.

PMID- 11224526
TI  - Costimulation of CD8alphabeta T cells by NKG2D via engagement by MIC induced on
      virus-infected cells.
AB  - NKG2D is an activating receptor that stimulates innate immune responses by
      natural killer cells upon engagement by MIC ligands, which are induced by
      cellular stress. Because NKG2D is also present on most CD8alphabeta T cells, it
      may modulate antigen-specific T cell responses, depending on whether MIC
      molecules--distant homologs of major histocompatibility complex (MHC) class I
      with no function in antigen presentation--are induced on the surface of pathogen
      infected cells. We found that infection by cytomegalovirus (CMV) resulted in
      substantial increases in MIC on cultured fibroblast and endothelial cells and was
      associated with induced MIC expression in interstitial pneumonia. MIC engagement
      of NKG2D potently augmented T cell antigen receptor (TCR)-dependent cytolytic and
      cytokine responses by CMV-specific CD28- CD8alphabeta T cells. This function
      overcame viral interference with MHC class I antigen presentation. Combined
      triggering of TCR-CD3 complexes and NKG2D induced interleukin 2 production and T
      cell proliferation. Thus NKG2D functioned as a costimulatory receptor that can
      substitute for CD28.

PMID- 11224527
TI  - PD-L2 is a second ligand for PD-1 and inhibits T cell activation.
AB  - Programmed death I (PD-I)-deficient mice develop a variety of autoimmune-like
      diseases, which suggests that this immunoinhibitory receptor plays an important
      role in tolerance. We identify here PD-1 ligand 2 (PD-L2) as a second ligand for
      PD-1 and compare the function and expression of PD-L1 and PD-L2. Engagement of PD
      1 by PD-L2 dramatically inhibits T cell receptor (TCR)-mediated proliferation and
      cytokine production by CD4+ T cells. At low antigen concentrations, PD-L2-PD-1
      interactions inhibit strong B7-CD28 signals. In contrast, at high antigen
      concentrations, PD-L2-PD-1 interactions reduce cytokine production but do not
      inhibit T cell proliferation. PD-L-PD-1 interactions lead to cell cycle arrest in
      G0/G1 but do not increase cell death. In addition, ligation of PD-1 + TCR leads
      to rapid phosphorylation of SHP-2, as compared to TCR ligation alone. PD-L
      expression was up-regulated on antigen-presenting cells by interferon gamma
      treatment and was also present on some normal tissues and tumor cell lines. Taken
      together, these studies show overlapping functions of PD-L1 and PD-L2 and
      indicate a key role for the PD-L-PD-1 pathway in regulatingT cell responses.

PMID- 11224529
TI  - The human genome: What next?

PMID- 11224528
TI  - B7-H3: a costimulatory molecule for T cell activation and IFN-gamma production.
AB  - We describe here a newly identified member of the human B7 family, designated B7
      homolog 3 (B7-H3), that shares 20-27% amino acid identity with other B7 family
      members. B7-H3 mRNA is not detectable in peripheral blood mononuclear cells,
      although it is found in various normal tissues and in several tumor cell lines.
      Expression of B7-H3 protein, however, can be induced on dendritic cells (DCs) and
      monocytes by inflammatory cytokines and a combination of phorbol myristate
      acetate (PMA) + ionomycin. Soluble B7-H3 protein binds a putative counter
      receptor on activated T cells that is distinct from CD28, cytotoxic T lymphocyte
      antigen 4 (CTLA-4), inducible costimulator (ICOS) and PD-1. B7-H3 costimulates
      proliferation of both CD4+ and CD8+ T cells, enhances the induction of cytotoxic
      T cells and selectively stimulates interferon gamma (IFN-gamma) production in the
      presence of T cell receptor signaling. In contrast, inclusion of antisense B7-H3
      oligonucleotides decreases the expression of B7-H3 on DCs and inhibits IFN-gamma
      production by DC-stimulated allogeneic T cells.Thus, we describe a newly
      identified costimulatory pathway that may participate in the regulation of cell
      mediated immune responses.

PMID- 11224530
TI  - Getting a bead on receptor movements.
AB  - Studies of populations of receptor proteins suggest that their number and
      location are highly regulated. Single-particle tracking of glycine receptors now
      reveals the direct movement of receptors between different clusters of the
      anchoring protein gephyrin.

PMID- 11224531
TI  - Drug delivery via the blood-brain barrier.
AB  - The blood-brain barrier forms a buffer against the systemic circulation. Now
      drugs administered to the brain are shown to be exported by a transporter to act
      at peripheral sites.

PMID- 11224532
TI  - Could plasticity of inhibition pattern pattern generators?
AB  - A modeling study shows that inhibitory synapse plasticity, guided by simple
      activity-dependent rules, can lead to appropriate phase relationships within an
      oscillating network.

PMID- 11224533
TI  - Late responses and perceptual awareness.
AB  - An electrophysiological study in monkey primary visual cortex reveals that a late
      component of neural activity is correlated with perceptual awareness of an
      object.

PMID- 11224535
TI  - Mice deficient in BACE1, the Alzheimer's beta-secretase, have normal phenotype
      and abolished beta-amyloid generation.

PMID- 11224536
TI  - BACE1 is the major beta-secretase for generation of Abeta peptides by neurons.

PMID- 11224537
TI  - NMDAR EPSC kinetics do not regulate the critical period for LTP at
      thalamocortical synapses.

PMID- 11224538
TI  - The functional anatomy of humor: segregating cognitive and affective components.

PMID- 11224539
TI  - Probing ion permeation and gating in a K+ channel with backbone mutations in the
      selectivity filter.
AB  - Potassium channels selectively conduct K+ ions across cell membranes, and use
      diverse mechanisms to control their gating. We studied ion permeation and gating
      of an inwardly rectifying K+ channel by individually changing the amide carbonyls
      of two conserved glycines lining the selectivity filter to ester carbonyls using
      nonsense suppression. Surprisingly, these backbone mutations do not significantly
      alter ion selectivity. However, they dramatically change the kinetics of single
      channel gating and produce distinct subconductance levels. The mutation at the
      glycine closer to the inner mouth of the pore also abolishes high-affinity
      binding of Ba2+ to the channel, indicating the importance of this position in ion
      stabilization in the selectivity filter. Our results demonstrate that K+ ion
      selectivity can be retained even with significant reduction of electronegativity
      in the selectivity filter, and that conformational changes of the filter arising
      from interactions between permeant ions and the backbone carbonyls contribute
      directly to channel gating.

PMID- 11224540
TI  - Muller glia are a potential source of neural regeneration in the postnatal
      chicken retina.
AB  - The retina of warm-blooded vertebrates is believed to be incapable of neural
      regeneration. Here we provide evidence that the retina of postnatal chickens has
      the potential to generate new neurons. In response to acute damage, numerous
      Muller glia re-entered the cell cycle, and shortly thereafter, expressed CASH-1,
      Pax6 and Chx10, transcription factors expressed by embryonic retinal progenitors.
      These progenitor-like cells transiently expressed neurofilament. Newly formed
      cells became distributed throughout the inner and outer nuclear layers of the
      retina, and remained for at least three weeks after damage. Some of these newly
      formed cells differentiated into retinal neurons, a few formed Muller glia, and
      most remained undifferentiated, with continued expression of Pax6 and Chx10.
      These cells continued to proliferate when grown in culture, with some
      differentiating into retinal neurons or Muller glia. We propose that, in response
      to damage, Muller glia in the retina are a potential source of neural
      regeneration.

PMID- 11224541
TI  - Fast and reversible trapping of surface glycine receptors by gephyrin.
AB  - Variations in receptor number at a given synapse are known to contribute to
      synaptic plasticity, but methods used to establish this idea usually do not allow
      for the determination of the dynamics of these phenomena. We used single-particle
      tracking to follow in real time, on the cell surface, movements of the glycine
      receptor (GlyR) with or without the GlyR stabilizing protein gephyrin. GlyR
      alternated within seconds between diffusive and confined states. In the absence
      of gephyrin, GlyR were mostly freely diffusing. Gephyrin induced long confinement
      periods spatially associated with submembranous clusters of gephyrin. However,
      even when most receptors were stabilized, they still frequently made transitions
      through the diffusive state. These data show that receptor number in a cluster
      results from a dynamic equilibrium between the pools of stabilized and freely
      mobile receptors. Modification of this equilibrium could be involved in
      regulation of the number of receptors at synapses.

PMID- 11224542
TI  - Nuclear calcium signaling controls CREB-mediated gene expression triggered by
      synaptic activity.
AB  - Information storage in the nervous system requires transcription triggered by
      synaptically evoked calcium signals. It has been suggested that translocation of
      calmodulin into the nucleus, initiated by submembranous calcium transients,
      relays synaptic signals to CREB. Here we show that in hippocampal neurons,
      signaling to CREB can be activated by nuclear calcium alone and does not require
      import of cytoplasmic proteins into the nucleus. The nucleus is particularly
      suited to integrate neuronal firing patterns, and specifies the transcriptional
      outputs through a burst frequency-to-nuclear calcium amplitude conversion.
      Calcium release from intracellular stores promotes calcium wave propagation into
      the nucleus, which is critical for CREB-mediated transcription by synaptic NMDA
      receptors. Pharmacological or genetic modulation of nuclear calcium may directly
      affect transcription-dependent memory and cognitive functions.

PMID- 11224544
TI  - Amphetamine selectively blocks inhibitory glutamate transmission in dopamine
      neurons.
AB  - Amphetamine is a highly addictive psychostimulant that promotes the release of
      the catecholamines dopamine and norepinephrine. Amphetamine-induced release of
      dopamine in the midbrain inhibits the activity of dopamine neurons through
      activation of D2 dopamine autoreceptors. Here we show that amphetamine may also
      excite dopamine neurons through modulation of glutamate neurotransmission.
      Amphetamine potently inhibits metabotropic glutamate receptor (mGluR)-mediated
      IPSPs in dopamine neurons, but has no effect on ionotropic glutamate receptor
      mediated EPSCs. Amphetamine desensitizes the mGluR-mediated hyperpolarization
      through release of dopamine, activation of postsynaptic alpha1 adrenergic
      receptors, and suppression of InsP3-induced calcium release from internal stores.
      By selectively suppressing the inhibitory component of glutamate-mediated
      transmission, amphetamine may promote burst firing of dopamine neurons. Through
      this mechanism, amphetamine may enhance phasic release of dopamine, which is
      important in the neural processing of reward.

PMID- 11224543
TI  - Transport of opioids from the brain to the periphery by P-glycoprotein:
      peripheral actions of central drugs.
AB  - Many peptides and transmitters found within the brain also have peripheral sites
      of action. We now demonstrate that the brain releases functionally active
      neurotransmitters/neuromodulators directly from the brain into the blood through
      a saturable P-glycoprotein (Pgp) transport system. Downregulating Pgp1 expression
      with antisense reduced the brain-to-blood transport of morphine, beta-endorphin
      and other opioids. Lowering Pgp expression significantly enhanced systemic
      morphine analgesia and prevented tolerance, but diminished the analgesic activity
      of centrally administered morphine, implying that supraspinal analgesia resulted
      from a combination of central and peripheral mechanisms activated by morphine
      transported from the brain to the blood. Similarly, mice with a disruption of the
      Mdr1a gene were more sensitive to systemic morphine and less sensitive to
      morphine given centrally. This ability of the Pgp transport system to pump
      functionally active compounds from the brain to periphery defines a potentially
      important mechanism for the central nervous system to modulate peripheral
      systems.

PMID- 11224545
TI  - PLC-beta1, activated via mGluRs, mediates activity-dependent differentiation in
      cerebral cortex.
AB  - During development of the cerebral cortex, the invasion of thalamic axons and
      subsequent differentiation of cortical neurons are tightly coordinated. Here we
      provide evidence that glutamate neurotransmission triggers a critical signaling
      mechanism involving the activation of phospholipase C-beta1 (PLC-beta1) by
      metabotropic glutamate receptors (mGluRs). Homozygous null mutation of either PLC
      beta1 or mGluR5 dramatically disrupts the cytoarchitectural differentiation of
      'barrels' in the mouse somatosensory cortex, despite segregation in the pattern
      of thalamic innervation. Furthermore, group 1 mGluR-stimulated phosphoinositide
      hydrolysis is dramatically reduced in PLC-beta1-/- mice during barrel
      development. Our data indicate that PLC-beta1 activation via mGluR5 is critical
      for the coordinated development of the neocortex, and that presynaptic and
      postsynaptic components of cortical differentiation can be genetically
      dissociated.

PMID- 11224546
TI  - A requirement for the immediate early gene Zif268 in the expression of late LTP
      and long-term memories.
AB  - The induction of long-term potentiation (LTP) in the dentate gyrus of the
      hippocampus is associated with a rapid and robust transcription of the immediate
      early gene Zif268. We used a mutant mouse with a targeted disruption of Zif268 to
      ask whether this gene, which encodes a zinc finger transcription factor, is
      required for the maintenance of late LTP and for the expression of long-term
      memory. We show that whereas mutant mice exhibit early LTP in the dentate gyrus,
      late LTP is absent when measured 24 and 48 hours after tetanus in the freely
      moving animal. In both spatial and non-spatial learning tasks, short-term memory
      remained intact, whereas performance was impaired in tests requiring long-term
      memory. Thus, Zif268 is essential for the transition from short- to long-term
      synaptic plasticity and for the expression of long-term memories.

PMID- 11224547
TI  - Activity-dependent modification of inhibitory synapses in models of rhythmic
      neural networks.
AB  - The faithful production of rhythms by many neural circuits depends critically on
      the strengths of inhibitory synaptic connections. We propose a model in which the
      strengths of inhibitory synapses in a central pattern-generating circuit are
      subject to activity-dependent plasticity. The strength of each synapse is
      modified as a function of the global activity of the postsynaptic neuron and by
      correlated activity of the pre- and postsynaptic neurons. This allows the self
      assembly, from random initial synaptic strengths, of two cells into reciprocal
      oscillation and three cells into a rhythmic triphasic motor pattern. This self
      assembly illustrates that complex oscillatory circuits that depend on multiple
      inhibitory synaptic connections can be tuned via simple activity-dependent rules.

PMID- 11224548
TI  - Two distinct modes of sensory processing observed in monkey primary visual cortex
      (V1).
AB  - Even salient sensory stimuli are sometimes not detected. What goes wrong in the
      brain in that case? Here we show that a late (> 100-ms) component of the neural
      activity in the primary visual cortex of the monkey is selectively suppressed
      when stimuli are not seen. As there is evidence that this activity depends on
      feedback from extrastriate areas, these findings suggest a specific role for
      recurrent processing when stimuli are reaching a perceptual level. Further
      results show that this perceptual level is situated between purely sensory and
      decision or motor stages of processing.

PMID- 11224549
TI  - The sensory nature of mnemonic representation in the primate prefrontal cortex.
AB  - A long-standing issue concerning the function of the primate dorsolateral
      prefrontal cortex is whether the activity of prefrontal neurons reflects the
      perceived sensory attributes of a remembered stimulus, or the decision to execute
      a motor response. To distinguish between these possibilities, we recorded
      neuronal activity from monkeys trained to make a saccade toward the brighter of
      two memoranda, under conditions of varied luminance. Our results indicated that
      during the delay period when sensory information was no longer available,
      neuronal discharge was modulated by the luminance of the stimulus appearing in
      the receptive field, and was directly correlated with psychophysical performance
      in the task. The findings suggest that although prefrontal cortex codes for a
      diversity of representations, including the decision for an impending response, a
      population of neurons maintains the dimensional attributes of remembered stimuli
      throughout the delay period, which allows for flexibility in the outcome of a
      mnemonic process.

PMID- 11224550
TI  - The evolution of brain activation during temporal processing.
AB  - Timing is crucial to many aspects of human performance. To better understand its
      neural underpinnings, we used event-related fMRI to examine the time course of
      activation associated with different components of a time perception task. We
      distinguished systems associated with encoding time intervals from those related
      to comparing intervals and implementing a response. Activation in the basal
      ganglia occurred early, and was uniquely associated with encoding time intervals,
      whereas cerebellar activation unfolded late, suggesting an involvement in
      processes other than explicit timing. Early cortical activation associated with
      encoding of time intervals was observed in the right inferior parietal cortex and
      bilateral premotor cortex, implicating these systems in attention and temporary
      maintenance of intervals. Late activation in the right dorsolateral prefrontal
      cortex emerged during comparison of time intervals. Our results illustrate a
      dynamic network of cortical-subcortical activation associated with different
      components of temporal information processing.

PMID- 11224551
TI  - Visuo-haptic object-related activation in the ventral visual pathway.
AB  - The ventral pathway is involved in primate visual object recognition. In humans,
      a central stage in this pathway is an occipito-temporal region termed the lateral
      occipital complex (LOC), which is preferentially activated by visual objects
      compared to scrambled images or textures. However, objects have characteristic
      attributes (such as three-dimensional shape) that can be perceived both visually
      and haptically. Therefore, object-related brain areas may hold a representation
      of objects in both modalities. Using fMRI to map object-related brain regions, we
      found robust and consistent somatosensory activation in the occipito-temporal
      cortex. This region showed clear preference for objects compared to textures in
      both modalities. Most somatosensory object-selective voxels overlapped a part of
      the visual object-related region LOC. Thus, we suggest that neuronal populations
      in the occipito-temporal cortex may constitute a multimodal object-related
      network.

PMID- 11224553
TI  - Making data available.

PMID- 11224554
TI  - The taming of the SNARE.

PMID- 11224556
TI  - Two insulators are not better than one.

PMID- 11224555
TI  - Charging two for the price of one.

PMID- 11224557
TI  - When FT-IR spectroscopy meets X-ray crystallography.

PMID- 11224558
TI  - Turning green to gold.

PMID- 11224559
TI  - Linus Pauling and the planar peptide bond.

PMID- 11224560
TI  - Picture story. Leak proof channel.

PMID- 11224561
TI  - Structural basis for anticodon recognition by discriminating glutamyl-tRNA
      synthetase.
AB  - Glutamyl-tRNA synthetases (GluRSs) are divided into two distinct types, with
      regard to the presence or absence of glutaminyl-tRNA synthetase (GlnRS) in the
      genetic translation systems. In the original 19-synthetase systems lacking GlnRS,
      the 'non-discriminating' GluRS glutamylates both tRNAGlu and tRNAGln. In
      contrast, in the evolved 20-synthetase systems with GlnRS, the 'discriminating'
      GluRS aminoacylates only tRNAGlu. Here we report the 2.4 A resolution crystal
      structure of a 'discriminating' GluRS.tRNAGlu complex from Thermus thermophilus.
      The GluRS recognizes the tRNAGlu anticodon bases via two alpha-helical domains,
      maintaining the base stacking. We show that the discrimination between the Glu
      and Gln anticodons (34YUC36 and 34YUG36, respectively) is achieved by a single
      arginine residue (Arg 358). The mutation of Arg 358 to Gln resulted in a GluRS
      that does not discriminate between the Glu and Gln anticodons. This change mimics
      the reverse course of GluRS evolution from anticodon 'non-dicsriminating' to
      'discriminating'.

PMID- 11224562
TI  - Structure of the RTP-DNA complex and the mechanism of polar replication fork
      arrest.
AB  - The coordinated termination of DNA replication is an important step in the life
      cycle of bacteria with circular chromosomes, but has only been defined at a
      molecular level in two systems to date. Here we report the structure of an
      engineered replication terminator protein (RTP) of Bacillus subtilis in complex
      with a 21 base pair DNA by X-ray crystallography at 2.5 A resolution. We also use
      NMR spectroscopic titration techniques. This work reveals a novel DNA interaction
      involving a dimeric 'winged helix' domain protein that differs from predictions.
      While the two recognition helices of RTP are in close contact with the B-form DNA
      major grooves, the 'wings' and N-termini of RTP do not form intimate contacts
      with the DNA. This structure provides insight into the molecular basis of polar
      replication fork arrest based on a model of cooperative binding and differential
      binding affinities of RTP to the two adjacent binding sites in the complete
      terminator.

PMID- 11224563
TI  - A domain-swapped RNase A dimer with implications for amyloid formation.
AB  - Bovine pancreatic ribonuclease (RNase A) forms two types of dimers (a major and a
      minor component) upon concentration in mild acid. These two dimers exhibit
      different biophysical and biochemical properties. Earlier we reported that the
      minor dimer forms by swapping its N-terminal alpha-helix with that of an
      identical molecule. Here we find that the major dimer forms by swapping its C
      terminal beta-strand, thus revealing the first example of three-dimensional (3D)
      domain swapping taking place in different parts of the same protein. This feature
      permits RNase A to form tightly bonded higher oligomers. The hinge loop of the
      major dimer, connecting the swapped beta-strand to the protein core, resembles a
      short segment of the polar zipper proposed by Perutz and suggests a model for
      aggregate formation by 3D domain swapping with a polar zipper.

PMID- 11224564
TI  - Structure of human biliverdin IXbeta reductase, an early fetal bilirubin IXbeta
      producing enzyme.
AB  - Biliverdin IXbeta reductase (BVR-B) catalyzes the pyridine nucleotide-dependent
      production of bilirubin-IXbeta, the major heme catabolite during early fetal
      development. BVR-B displays a preference for biliverdin isomers without
      propionates straddling the C10 position, in contrast to biliverdin IXalpha
      reductase (BVR-A), the major form of BVR in adult human liver. In addition to its
      tetrapyrrole clearance role in the fetus, BVR-B has flavin and ferric reductase
      activities in the adult. We have solved the structure of human BVR-B in complex
      with NADP+ at 1.15 A resolution. Human BVR-B is a monomer displaying an
      alpha/beta dinucleotide binding fold. The structures of ternary complexes with
      mesobiliverdin IValpha, biliverdin IXalpha, FMN and lumichrome show that human
      BVR-B has a single substrate binding site, to which substrates and inhibitors
      bind primarily through hydrophobic interactions, explaining its broad
      specificity. The reducible atom of both biliverdin and flavin substrates lies
      above the reactive C4 of the cofactor, an appropriate position for direct hydride
      transfer. BVR-B discriminates against the biliverdin IXalpha isomer through
      steric hindrance at the bilatriene side chain binding pockets. The structure also
      explains the enzyme's preference for NADP(H) and its B-face stereospecificity.

PMID- 11224565
TI  - Crystal structure of rat biliverdin reductase.
AB  - Biliverdin reductase (BVR) is a soluble cytoplasmic enzyme that catalyzes the
      conversion of biliverdin to bilirubin using NADH or NADPH as electron donor.
      Bilirubin is a significant biological antioxidant, but it is also neurotoxic and
      the cause of kernicterus. In this study, we have determined the crystal structure
      of rat BVR at 1.4 A resolution. The structure contains two domains: an N-terminal
      domain characteristic of a dinucleotide binding fold (Rossmann fold) and a C
      terminal domain that is predominantly an antiparallel six-stranded beta-sheet.
      Based on this structure, we propose modes of binding for NAD(P)H and biliverdin,
      and a possible mechanism for the enzyme.

PMID- 11224566
TI  - Single-molecule tracking of myosins with genetically engineered amplifier
      domains.
AB  - We combined protein engineering and single molecule measurements to directly
      record the step size of a series of myosin constructs with shortened and
      elongated artificial neck domains. Our results show that the step size has a
      clear linear dependence on the length of the neck domain and we also established
      that mechanical amplification in the myosin motor is based on a rotation of the
      neck domain relative to the actin-bound head. For all our constructs, including
      those with artificial necks, the magnitude of the neck rotation concurrent with
      the displacement step was approximately 30 degrees. The engineered change in the
      step size of myosin marks a significant advance in our ability to selectively
      modify the functional properties of molecular motors.

PMID- 11224567
TI  - Molecular determinants of complex formation between Clp/Hsp100 ATPases and the
      ClpP peptidase.
AB  - The Clp/Hsp100 ATPases are hexameric protein machines that catalyze the
      unfolding, disassembly and disaggregation of specific protein substrates in
      bacteria, plants and animals. Many family members also interact with peptidases
      to form ATP-dependent proteases. In Escherichia coli, for instance, the ClpXP
      protease is assembled from the ClpX ATPase and the ClpP peptidase. Here, we have
      used multiple sequence alignments to identify a tripeptide 'IGF' in E. coli ClpX
      that is essential for ClpP recognition. Mutations in this IGF sequence, which
      appears to be part of a surface loop, disrupt ClpXP complex formation and prevent
      protease function but have no effect on other ClpX activities. Homologous
      tripeptides are found only in a subset of Clp/Hsp100 ATPases and are a good
      predictor of family members that have a ClpP partner. Mapping of the IGF loop
      onto a homolog of known structure suggests a model for ClpX-ClpP docking.

PMID- 11224568
TI  - Prediction and confirmation of a site critical for effector regulation of RGS
      domain activity.
AB  - A critical challenge of structural genomics is to extract functional information
      from protein structures. We present an example of how this may be accomplished
      using the Evolutionary Trace (ET) method in the context of the regulators of G
      protein signaling (RGS) family. We have previously applied ET to the RGS family
      and identified a novel, evolutionarily privileged site on the RGS domain as
      important for regulating RGS activity. Here we confirm through targeted
      mutagenesis of RGS7 that these ET-identified residues are critical for RGS domain
      regulation and are likely to function as global determinants of RGS function. We
      also discuss how the recent structure of the complex of RGS9, Gt/i1alpha-GDP-AlF4
      and the effector subunit PDEgamma confirms their contact with the effector-G
      protein interface, forming a structural pathway that communicates from the
      effector-contacting surface of the G protein and RGS catalytic core domain to the
      catalytic interface between Galpha and RGS. These results demonstrate the
      effectiveness of ET for identifying binding sites and efficiently focusing
      mutational studies on their key residues, thereby linking raw sequence and
      structure data to functional information.

PMID- 11224569
TI  - Predicting the emergence of antibiotic resistance by directed evolution and
      structural analysis.
AB  - Directed evolution can be a powerful tool to predict antibiotic resistance.
      Resistance involves the accumulation of mutations beneficial to the pathogen
      while maintaining residue interactions and core packing that are critical for
      preserving function. The constraint of maintaining stability, while increasing
      activity, drastically reduces the number of possible mutational combination
      pathways. To test this theory, TEM-1 beta-lactamase was evolved using a
      hypermutator E. coli-based directed evolution technique with cefotaxime
      selection. The selected mutants were compared to two previous directed evolution
      studies and a database of clinical isolates. In all cases, evolution resulted in
      the generation of the E104K/M182T/G238S combination of mutations ( approximately
      500-fold increased resistance), which is equivalent to clinical isolate TEM-52.
      The structure of TEM-52 was determined to 2.4 A. G238S widens access to the
      active site by 2.8 A whereas E104K stabilizes the reorganized topology. The M182T
      mutation is located 17 A from the active site and appears to be a global
      suppressor mutation that acts to stabilize the new enzyme structure. Our results
      demonstrate that directed evolution coupled with structural analysis can be used
      to predict future mutations that lead to increased antibiotic resistance.

PMID- 11224570
TI  - Structure of the cooperative allosteric anthranilate synthase from Salmonella
      typhimurium.
AB  - We have determined the X-ray crystal structure of the cooperative anthranilate
      synthase heterotetramer from Salmonella typhimurium at 1.9 A resolution with the
      allosteric inhibitor l-tryptophan bound to a regulatory site in the TrpE subunit.
      Tryptophan binding orders a loop that in turn stabilizes the inactive T state of
      the enzyme by restricting closure of the active site cleft. Comparison with the
      structure of the unliganded, noncooperative anthranilate synthase heterotetramer
      from Sulfolobus solfataricus shows that the two homologs have completely
      different quarternary structures, even though their functional dimer pairs are
      structurally similar, consistent with differences in the cooperative behavior of
      the enzymes. The structural model rationalizes mutational and biochemical studies
      of the enzyme and establishes the structural differences between cooperative and
      noncooperative anthranilate synthase homologs.

PMID- 11224572
TI  - GrpE accelerates peptide binding and release from the high affinity state of
      DnaK.
AB  - The Escherichia coli nucleotide exchange factor GrpE accelerates the rate of ADP
      dissociation from high affinity ADP-DnaK, thus enabling ATP binding and
      transition to the low affinity state. We show here that GrpE, in the absence of
      ATP, accelerates the rates of the forward and reverse reaction ADP-DnaK-P right
      harpoon over left harpoon ADP-DnaK + P, where P denotes peptide substrate.
      Specifically, the binding of GrpE to an ADP-DnaK-P (or DnaK-P) complex increases
      koff and kon by approximately 200-fold and approximately 60-fold, respectively.
      The results are consistent with a GrpE- induced conformational change in the C
      terminal polypeptide binding domain of an ADP-DnaK molecule, which results in a
      unique low affinity intermediate from which peptide can dissociate. A simulation
      of peptide dissociation from DnaK as a function of the [ATP] / [ADP] ratio shows
      that GrpE induced peptide dissociation from ADP-DnaK is important at elevated
      cellular concentrations of ADP, which typically occur upon stress.

PMID- 11224571
TI  - The L3 loop and C-terminal phosphorylation jointly define Smad protein
      trimerization.
AB  - Smad proteins mediate the transforming growth factor beta responses. C-terminal
      phosphorylation of R-Smads leads to the recruitment of Smad4 and the formation of
      active signaling complexes. We investigated the mechanism of phosphorylation
      induced Smad complex formation with an activating pseudo-phosphorylated Smad3.
      Pseudo-phosphorylated Smad3 has a greater propensity to homotrimerize, and
      recruits Smad4 to form a heterotrimer containing two Smad3 and one Smad4. The
      trimeric interaction is mediated through conserved interfaces to which
      tumorigenic mutations map. Furthermore, a conserved Arg residue within the L3
      loop, located near the C-terminal phosphorylation sites of the neighboring
      subunit, is essential for trimerization. We propose that the phosphorylated C
      terminal residues interact with the L3 loop of the neighboring subunit to
      stabilize the trimer interaction.

PMID- 11224573
TI  - Vam3p structure reveals conserved and divergent properties of syntaxins.
AB  - Syntaxins and Sec1/munc18 proteins are central to intracellular membrane fusion.
      All syntaxins comprise a variable N-terminal region, a conserved SNARE motif that
      is critical for SNARE complex formation, and a transmembrane region. The N
      terminal region of neuronal syntaxin 1A contains a three-helix domain that folds
      back onto the SNARE motif forming a 'closed' conformation; this conformation is
      required for munc18-1 binding. We have examined the generality of the structural
      properties of syntaxins by NMR analysis of Vam3p, a yeast syntaxin essential for
      vacuolar fusion. Surprisingly, Vam3p also has an N-terminal three-helical domain
      despite lacking apparent sequence homology with syntaxin 1A in this region.
      However, Vam3p does not form a closed conformation and its N-terminal domain is
      not required for binding to the Sec1/munc18 protein Vps33p, suggesting that
      critical distinctions exist in the mechanisms used by syntaxins to govern
      different types of membrane fusion.

PMID- 11224575
TI  - Structures of two natural product methyltransferases reveal the basis for
      substrate specificity in plant O-methyltransferases.
AB  - Chalcone O-methyltransferase (ChOMT) and isoflavone O-methyltransferase (IOMT)
      are S-adenosyl-l-methionine (SAM) dependent plant natural product
      methyltransferases involved in secondary metabolism in Medicago sativa (alfalfa).
      Here we report the crystal structure of ChOMT in complex with the product S
      adenosyl-l-homocysteine and the substrate isoliquiritigenin (4,2',4'
      trihydroxychalcone) refined to 1.8 A as well as the crystal structure of IOMT in
      complex with the products S-adenosyl-l-homocysteine and isoformononetin (4'
      hydroxy-7-methoxyisoflavone) refined to 1.4 A. These two OMTs constitute the
      first plant methyltransferases to be structurally characterized and reveal a
      novel oligomerization domain and the molecular determinants for substrate
      selection. As such, this work provides a structural basis for understanding the
      substrate specificity of the diverse family of plant OMTs and facilitates the
      engineering of novel activities in this extensive class of natural product
      biosynthetic enzymes.

PMID- 11224576
TI  - Beyond the millennium: what can be done to improve child health in South Asia?

PMID- 11224574
TI  - Structure of the I1 early intermediate of photoactive yellow protein by FTIR
      spectroscopy.
AB  - To understand how proteins translate the energy of sunlight into defined
      conformational changes, we have measured the photocycle reactions of photoactive
      yellow protein (PYP) using time-resolved step scan Fourier transform infrared
      (FTIR) spectroscopy. Global fit analysis yielded the same apparent time constants
      for the reactions of the chromophore, the protonation changes of protein side
      chains and the protein backbone motions, indicating that the light cycle
      reactions are synchronized. Changes in absorbance indicate that there are at
      least four intermediates (I1, I1', I2, I2'). In the intermediate I1, the dark
      state hydrogen bond from Glu 46 to the aromatic ring of the p-hydroxycinnamoyl
      chromophore is preserved, implying that the chromophore undergoes trans to cis
      isomerization by flipping, not the aromatic ring, but the thioester linkage with
      the protein. This excludes an I1 structural model proposed on the basis of time
      resolved Laue crystallography, but does agree with the cryotrapped structure of
      an I1 precursor.

PMID- 11224577
TI  - Strategy for preventing vertical transmisssion of HIV : Bombay experience.
AB  - OBJECTIVE: To evaluate the efficacy of an interventional regime to reduce the
      perinatal mode of transmission of human immunodeficiency virus (HIV). DESIGN:
      Prospective. SETTING: Perinatal HIV clinic at a university affiliated maternity
      hospital. SUBJECT & METHODS: After adequate counseling, consenting HIV positive
      women were offered perinatal intervention: (i) administration of 400 mg of
      zidovudine (AZT) per day for the last 6 weeks of the antenatal period; (ii)
      delivery by elective Caesarian section before rupture of membrances; (iii) oral
      AZT powder in the dose of 8 mg per kilogram daily to the infant for the first 6
      weeks of life; and (iv) avoidance of breast milk. The infants were scheduled for
      regular follow-up for at least 18 months. A definitive diagnosis of infectivity
      in the infant was ascertained by two positive enzyme-linked immunosorbent assays
      (ELISA) at the age of 9 months and between 15 to 18 months. RESULTS: Of the 107
      mother-infant pairs enrolled, 22 infants were lost to follow-up, 15 were under 18
      months of age at the time of this analysis and 2 infants died without a
      diagnosis. Of the remaining 68 infants followed up, 4 tested HIV positive at 18
      months. Of the 229 women-infant pairs who did not receive perinatal intervention,
      55 infants followed up to 15-18 months were found to be infected. CONCLUSION:
      This interventional strategy significantly reduced the mother to child
      transmission of HIV. However, the results need to be substantiated by larger
      studies.

PMID- 11224578
TI  - Compensatory hyperparathyroidism following high fluoride ingestion - a clinico -
      biochemical correlation.
AB  - OBJECTIVE: To evaluate the effect of varying ingestion of drinking water
      containing high fluorides and its effect on serum parathyroid hormone. DESIGN:
      Cross sectional clinical study. SETTING: S.M.S. Medical College, Jaipur. SUBJECT:
      200 children were selected from four areas (50 from each area) consuming water
      containing 2.4, 4.6, 5.6 and 13.5 mg/l of fluoride. All children were in an age
      group of 6 to 12 years. METHODS: All children were graded for clinical,
      radiological and dental fluorosis and biochemical estimations were made for serum
      calcium, serum and urinary fluoride and serum parathyroid hormone. RESULTS: Serum
      calcium levels were well within normal range in the patients of all areas but an
      increase in serum parathyroid levels (S. PTH) was noted. The increased S. PTH was
      well correlated with increase in fluoride ingestion. The severity of clinical and
      skeletal fluorosis was observed to increase with increase in S. PTH
      concentration. CONCLUSIONS: High Fluoride ingestion has a definite relationship
      with increased parathyroid hormone secretion, which may be responsible for
      maintaining serum calcium levels and may have a role in toxic manifestations of
      fluorosis.

PMID- 11224579
TI  - Mechanical ventilation in pediatric practice.

PMID- 11224580
TI  - Mycoplasma pneumoniae antibodies in children with acute respiratory infection.

PMID- 11224581
TI  - Etiological factors of malnutrition among infants in two urban slums of Delhi.

PMID- 11224582
TI  - Neurological prognosis in term newborns with neonatal indirect
      hyperbilirubinemia.

PMID- 11224583
TI  - Evolution of otogenic brain abscess and management protocol.

PMID- 11224584
TI  - Perinatal outcome in pregnancy associated hypertension.

PMID- 11224585
TI  - Post-transfusion graft versus host disease - an under recognized entity.

PMID- 11224586
TI  - Factor X deficiency and hemophilia A : occurrence of two different coagulation
      defects in a family.

PMID- 11224587
TI  - Pleural empyema due to group B Salmonella in a child with diarrhea.

PMID- 11224588
TI  - Thoracic epidural neurilemmoma: a rare cause of childhood paraparesis.

PMID- 11224589
TI  - Chromosomes 6/7 translocation t(6:7)(q15;32) presenting as multiple pterygium
      syndrome.

PMID- 11224590
TI  - Crouzon's syndrome with hydrocephalus.

PMID- 11224591
TI  - Technical differences between vaccines: convincing or confusing.

PMID- 11224593
TI  - Salmonella enteritidis meningitis in an infant.

PMID- 11224594
TI  - Childhood hemangiopericytoma.

PMID- 11224595
TI  - Poisoning in children.

PMID- 11224596
TI  - Use of paraldehyde in neonates - an experience.

PMID- 11224597
TI  - Sarcomatoid differentiation in renal cell carcinoma: a study of 101 cases.
AB  - Sarcomatoid renal cell carcinoma is not a distinct histologic entity and
      represents high-grade transformation in different subtypes of renal cell
      carcinoma. It is not known whether any particular histologic type has a
      predilection for sarcomatoid change or whether the primary histologic type of
      renal carcinoma undergoing sarcomatoid change affects prognosis. Of 952
      consecutively histologically subtyped renal cell carcinomas, the incidence of
      sarcomatoid differentiation was 8% in conventional (clear cell) renal carcinoma,
      3% in papillary renal carcinoma, 9% in chromophobe renal carcinoma, 29% in
      collecting duct carcinoma, and 11% in unclassified renal cell carcinoma. One
      hundred one renal cell carcinomas with sarcomatoid change were studied, and
      clinicopathologic parameters were correlated with outcome. The mean age of
      patients was 60 years (range, 33-80 years), and the male-to-female ratio was
      1.6:1. The median tumor size was 9.2 cm (range, 3-25 cm). The primary histologic
      subtype of the carcinoma component was conventional (clear cell) renal carcinoma
      in 80 cases, papillary renal carcinoma in eight, chromophobe renal carcinoma in
      seven, collecting duct carcinoma in two, and unclassified renal cell carcinoma in
      four. The sarcomatoid component resembled fibrosarcoma in 54 cases, malignant
      fibrous histiocytoma in 44, undifferentiated sarcoma (not otherwise specified) in
      three with focal rhabdomyosarcomatous component in two of them. The spindled
      elements accounted for 1% to 99% of the sampled tumor (median, 40%; mean 45%).
      The histologic grade of the spindled elements was intermediate to high in 92
      cases and low in nine cases. Most cases were TNM stages III and IV (seven stage
      I, six stage II, 63 stage III, and 25 stage IV). Follow-up was available in 88
      patients; 61 (69%) patients died of disease and had a median survival time of 19
      months. Distant metastases, most frequently to the lungs, were documented in 51
      (66%) of 77 patients who had available clinical information regarding distant
      metastasis. The disease-specific survival rate was 22% and 13% after 5 and 10
      years, respectively, compared with a cohort of renal cell carcinomas without
      sarcomatoid change with a 5-and 10-year disease-specific survival of 79% and 76%,
      respectively. Kaplan-Meier survival analysis showed that tumors with high TNM
      stage (p = 0.0027), at least 50% sarcomatoid component (p = 0.0453), and
      angiolymphatic invasion (p = 0.0282) were associated with decreased survival
      rates. The primary histologic subtype of the carcinoma component and the type and
      grade of the sarcomatoid component did not affect survival. In a Cox proportional
      hazard regression model, TNM stage appeared to be the only significant variable
      in predicting outcome among renal cell carcinomas with sarcomatoid change (p =
      0.018; risk ratio, 6.984 and 8.439). Compared with a cohort of renal cell
      carcinomas without sarcomatoid change, sarcomatoid tumors tended to present at a
      more advanced stage (p = 0.0001). Also, when adjusted for stage, necrosis, and
      tumor size, patients with tumors with sarcomatoid differentiation had a worse
      prognosis than did patients with tumors without sarcomatoid change (p = 0.0001).
      In conclusion, sarcomatoid change in renal cell carcinoma portends a worse
      prognosis. Because tumors with even a small component of sarcomatoid change may
      have an adverse outcome, this finding, when present, should be noted in the
      surgical pathology report.

PMID- 11224598
TI  - Hepatosplenic alphabeta T-cell lymphomas: a report of 14 cases and comparison
      with hepatosplenic gammadelta T-cell lymphomas.
AB  - Hepatosplenic gammadelta T-cell lymphoma is a distinct entity, characterized by
      occurrence in young adult males with hepatosplenomegaly, B-symptoms, peripheral
      blood cytopenias, and no lymphadenopathy; lymphomatous infiltrates in the splenic
      red pulp, hepatic sinusoids, and bone marrow sinuses; T-cell receptor (TCR)
      gammadelta chains and a cytotoxic T-cell phenotype; isochromosome 7q; and an
      aggressive clinical course. In comparison, this study describes the
      clinicopathologic features of 14 hepatosplenic T-cell lymphomas expressing TCR
      alphabeta chains. They occurred in 11 women and 3 men with a median age of 36
      years. Clinical presentation was similar to that described previously for
      hepatosplenic gammadelta T-cell lymphomas, except for the female preponderance
      and age distribution (5 patients younger than 13 years of age and 5 patients
      older than 50 years of age). Disease distribution was primarily in the splenic
      red pulp and hepatic sinusoids, although liver infiltrates were largely
      periportal in four cases. Bone marrow involvement, observed in eight patients,
      was usually interstitial and/or within the sinuses. Lymph nodes were involved in
      five patients, although lymphadenopathy was demonstrable in only two. Ten cases
      were composed of intermediate-size tumor cells with round/oval nuclei, slightly
      dispersed chromatin, inconspicuous nucleoli, and scant to moderate amounts of
      cytoplasm. Four lymphomas contained primarily large cells with irregular nuclei,
      dispersed chromatin, discernible nucleoli, and moderate to abundant cytoplasm.
      Tumor cells in all 14 lymphomas were cytotoxic alphabeta T-cells; 13 co-expressed
      natural killer cell-associated antigens and showed T-cell clonality. Three
      lymphomas were associated with Epstein-Barr virus. Two of four cases had an
      isochromosome 7q. Eleven patients are dead, eight within a year of diagnosis, and
      two patients have maintained complete remissions after combination chemotherapy.
      These data show that hepatosplenic T-cell lymphomas include an alphabeta-subtype.
      This group, along with the previously recognized gammadelta group, should be
      recognized as phenotypically heterogeneous subtypes of the same disease entity.

PMID- 11224599
TI  - Pathologic and clinical features of 77 Hodgkin's lymphoma patients treated in a
      lymphoma protocol (LNH87): a GELA study.
AB  - Between 1987 and 1993, 77 of 2855 lymphomas included in the LNH87 protocol of the
      GELA as non-Hodgkin lymphoma (NHL) and reviewed by a panel of pathologists had a
      diagnosis changed to Hodgkin lymphoma (HL). Some of these lymphomas had been
      initially interpreted as anaplastic large-cell lymphoma Hodgkin-like (ALCL-HL
      subtype). The purpose of this study was to analyze the histologic pitfalls
      initially encountered, to define more clearly the diagnostic criteria of
      lymphomas placed in the gray zone around HL, and to follow the survival of these
      77 patients affected with HL and initially treated with NHL regimens. The 77
      cases of HL were reviewed by three hematopathologists and immunostained with a
      large panel of antibodies, including CD30, CD15, CD3, CD20, CD45, CD43, LMP-1,
      EMA, BNH-9, TiA1, and ALK1. Each case was classified according to the Lukes-Rye
      system and the British National Lymphoma Investigation (BNLI) grading. The
      initial clinical presentation of patients was analyzed, and the overall and event
      free survival rates of the 77 patients were estimated. Among the 77 HLs, 46 were
      misinterpreted as NHL by primary individual pathologists (12 as ALCL, 8 as ALCL
      HL, 12 as peripheral T-cell lymphoma (PTCL), 6 as B-cell lymphoma, and 8 as
      unclassifiable NHL). The other 31 cases had been first considered by the panel as
      consistent with ALCL-HL (n = 18) or with PTCL (n = 13) and were changed later in
      view of an immunophenotype concordant with HL. Fifty-five percent of the patients
      completed the full NHL treatment. The 5-year event-free and overall survival
      rates were 54% and 77%, respectively. The current results indicate that lymphomas
      initially called ALCL-HL should not be regarded as a variant of ALCL, but as HL.
      The clinical consequences of misdiagnoses seem to be a lower event-free survival
      rate compared with that of classical HL, probably because of more relapses of
      initially inappropriately treated HL.

PMID- 11224600
TI  - Primary cutaneous large B-cell lymphoma: the relation between morphology,
      clinical presentation, immunohistochemical markers, and survival.
AB  - The histogenesis, morphology, immunophenotype, and clinical behavior of cutaneous
      large B-cell lymphomas (CLBCL) are largely a matter of controversy. We performed
      an investigation to determine whether CLBCL have features that differentiate them
      from other large B-cell lymphomas and whether CLBCL is itself a heterogeneous
      group. To this end, we reviewed the main characteristics of a series of 32 cases
      of LBCL found in the skin. We reviewed the clinical findings and paraffin
      sections of the tumors from these 32 patients. The immunohistochemical study
      performed included p53, MIB1, Bcl2, Bcl6, and CD10 markers. We carried out
      statistical analysis of these data (univariate and multivariate), seeking an
      association between the features of the tumors and clinical outcome, as defined
      by failure-free survival time. Only one patient died as a consequence of the
      lymphoma. Nevertheless, the accumulated probability of survival without failure
      at 48 months was 0.46. The number, type, and localization of the lesions were not
      associated with variations in either survival or failure-free survival. The
      expression of p53 was negative in this group of CLBCL, whereas Bcl-2 expression
      or localization in the lower leg did not relate to any other significant feature.
      Histologic examination of the cases disclosed three different groups: Grade III
      follicular lymphomas (FLs), monomorphous large B-cell lymphomas (LBCL type I),
      and LBCL with an admixed component of small B-lymphocytes (LBCL type II). Grade
      III FL (11 cases) tended to be found in the head and neck and showed CD10
      expression in a majority of cases. A higher probability of lymph node relapses
      was associated with cases located in the head and neck and with CD10+ tumors.
      Cutaneous large B-cell lymphomas are indolent tumors, but follow an insidious
      course. Our data support the interpretation that CLBCL is a heterogeneous
      condition; comprises some LBCL derived from CD10+ germinal center cells which
      manifests more frequently as tumors in the head and neck region, with an
      increased probability of relapse in lymph nodes [1] and has some distinctive
      morphologic features. The existence of a component of small B-cells within the
      other CLBCL could lend support to the theory that some of these tumors, more than
      arise de novo, may have originated in preexistent small B-cell lymphomas, but no
      firm evidence of this is provided in this study.

PMID- 11224601
TI  - Melanoma associated with blue nevus and melanoma mimicking cellular blue nevus: a
      clinicopathologic study of 10 cases on the spectrum of so-called 'malignant blue
      nevus'.
AB  - The term "malignant blue nevus" refers to a rare and heterogeneous group of
      melanomas that arise in several clinical settings. This includes melanomas
      arising in association with a common or cellular blue nevus and those arising de
      novo and resembling cellular blue nevi. We reviewed the clinicopathologic
      features of 10 cases of malignant blue nevi. Six cases proved to be de novo
      melanoma mimicking cellular blue nevus, but lacking a clear-cut benign component.
      Two melanomas arose in association with a common blue nevus, and two with a
      cellular blue nevus. The patients' (5 males, 5 females) ages ranged from 11 to 77
      years (average age, 48.1 years). The head and neck was the most common location
      (6 of 10 patients), with five scalp tumors. Four tumors were located on the
      trunk; none was located on the extremities. Tumor size ranged from 0.5 to 2.2 cm
      (average size, 1.1cm). Most lesions had been present for many years before
      surgical removal. Pigmented dendritic cells were observed in 9 of 10 cases. The
      malignant and benign components were easily distinguished in the four cases that
      arose in association with a common or cellular blue nevus. Abrupt transition
      between a benign blue nevus and melanoma was readily recognized at scanning
      magnification as distinctive nodules of epithelioid to spindled cells with a
      sheet-like growth pattern. In all cases, malignancy was evidenced by increased
      mitotic rate, necrosis, nuclear atypia, pleomorphism, hyperchromasia, and
      prominent nucleoli. All 7 patients with follow-up information experienced
      recurrence (3 patients) or metastasis (4 patients). Three patients died of
      disease. Malignant blue nevus is a heterogeneous group of melanomas that are
      highly aggressive and often lethal, with a propensity for metastasis to the lymph
      nodes and lungs.

PMID- 11224602
TI  - Allograft liver biopsy in patients with Epstein-Barr virus-associated
      posttransplant lymphoproliferative disease.
AB  - Allograft liver biopsy specimens (n = 24) obtained in the clinical setting of
      primarily extrahepatic posttransplant lymphoproliferative disease (PTLD) were
      studied for histopathology, lymphocyte subsets, and Epstein-Barr virus (EBV)
      encoded EBER RNA. Acute rejection was found in 20 (83.3%) of 24 biopsy specimens
      and graded as indeterminate in 7 (35%) of 20 (35%), mild in 3 (15%) of 20, and
      moderate in 10 (50%) of 20 cases. EBV hepatitis was the primary diagnosis in two
      biopsy specimens and a secondary finding in six others. Four biopsy specimens
      showed nonspecific reactive hepatitis, and five showed recurrence of primary
      liver disease. Immunoperoxidase staining showed primarily T cells. EBER RNA was
      detected in 14 (58.3%) of 24 biopsy specimens: 12 (60%) of 20 with and 2 (50%) of
      4 without acute rejection. Antirejection therapy resulted in complete or partial
      response in 4 (36.3%) of 11 and 7 (63.7%) of 11 treated cases, respectively,
      despite the presence of EBV-infected cells in some tissues. Subsequent follow-up
      showed early or late chronic rejection in 6 (25%) of 24 patients. Gamma glutamyl
      transferase, a marker for early or late chronic rejection, was greater than five
      times the upper limit of normal in 9 (37.5%) of 24 patients. In conclusion, liver
      biopsy specimens in patients with PTLD show a spectrum of pathologic changes.
      Rejection may be treated even if EBV is concurrently present. Long-term graft is
      suboptimal, because low immunosuppression results in a tendency to develop
      chronic rejection.

PMID- 11224603
TI  - Centrally necrotizing carcinomas of the breast: a distinct histologic subtype
      with aggressive clinical behavior.
AB  - Most breast carcinomas exhibit ductal differentiation. However, recognition of
      less common histologic patterns provides clinically useful data. This report
      describes a distinctive subtype of breast carcinoma that we have termed
      "centrally necrotizing carcinoma" (CNC; in this study, N = 34), which is
      characterized by an unusual and aggressive natural history. Centrally necrotizing
      carcinomas are composed of well-circumscribed, unicentric nodules with extensive
      central necrosis that are surrounded by a narrow rim of viable high-grade tumor
      cells. These tumor cells show minimal ductal differentiation (i.e., tubule
      formation), but are usually associated with focal ductal carcinoma in situ. The
      mean age of the patients in this study was 57.5 +/- 11.6 years, and the mean
      tumor size was 2.5 +/- 1.2 cm. Twenty-eight percent of the patients had positive
      axillary lymph nodes (mean number of lymph nodes involved, 2.1 +/- 1.2). Ninety
      four percent of cases were negative for estrogen and progesterone receptors. In
      21 patients (62%), local and/or distant recurrences developed (median time to
      recurrence, 16.2 months), and, to date, 20 have died from breast cancer (median
      time to death, 22.5 months). Progression of disease (defined as the development
      of either a recurrence or death resulting from disease) occurred in 24 patients
      (71%). Comparison with a set of 26 poorly differentiated ductal carcinomas with
      (nonextensive, patchy) necrosis matched for age, tumor size, and lymph node
      status showed a significantly worse progression-free survival rate for the CNC
      group (p < 0.004). We conclude that CNC is an uncommon but readily identifiable
      subtype of breast carcinoma and is characterized by early systemic metastasis and
      an accelerated clinical course.

PMID- 11224604
TI  - Carcinosarcoma of the uterine cervix: a report of eight cases with
      immunohistochemical analysis and evaluation of human papillomavirus status.
AB  - Carcinosarcomas (malignant Mullerian mixed tumors [MMMTs]) of the uterine cervix
      are rare neoplasms. This report describes the morphology, immunohistochemical
      profiles, and human papillomavirus (HPV) status of eight cervical MMMTs.
      Patients' ages ranged from 32 to 93 years (mean, 61 years). Seven cases showed in
      situ squamous cell carcinoma (SCC). The invasive epithelial component (EC) was
      composed of combined adenoid basal carcinoma, basaloid SCC, and adenoid cystic
      carcinoma (ACC) in two cases. Keratinizing SCC, large cell nonkeratinizing SCC,
      undifferentiated carcinoma, and basaloid SCC predominated in the remaining
      tumors, one of which had admixed ACC. The sarcomatous component (SC) was
      homologous and spindled with admixed myxoid areas in three lesions. The ECs and
      SCs in six MMMTs showed dual immunostaining with epithelial membrane antigen and
      the pan-keratin marker, MNF116. The SC was vimentin-positive in seven cases. Five
      tumors had a vimentin-positive EC. The SC was positive for muscle specific actin
      and/or smooth muscle actin in seven lesions, of which four were desmin-positive.
      Polymerase chain reaction (PCR) using GP5+/GP6+ L1 consensus primers detected HPV
      DNA in all eight cases. Nonisotopic in situ hybridization with digoxigenin
      labeled probes to HPV types 6, 11, 16, 18, 31 and 33 demonstrated integrated HPV
      16 in three cases, not only in the EC, but also in nuclei of the SC. This is the
      first study to implicate HPV in the evolution of cervical MMMTs. The above
      observations lend support to a metaplastic theory of histogenesis.

PMID- 11224606
TI  - Morphologic expressions of urothelial carcinoma in situ: a detailed evaluation of
      its histologic patterns with emphasis on carcinoma in situ with microinvasion.
AB  - The recently proposed World Health Organization/International Society of
      Urological Pathology (WHO/ISUP) consensus classification of flat urothelial
      lesions expands the definition traditionally used for urothelial (transitional
      cell) carcinoma in situ (CIS), basing its diagnosis predominantly on the severity
      of cytologic changes. Lesions now encompassed within the diagnosis of CIS exhibit
      an array of cytologic and architectural features, which have not been documented
      in detail. In this study, cases were examined with respect to histologic patterns
      and microinvasion (invasion into the lamina propria to a depth of less than 2
      mm). Five major patterns of CIS, often occurring in the same specimen (160
      patterns in 77 cases), were noted. Common to each pattern was the presence of
      high-grade cytologic atypia, the definitional feature. The patterns found include
      1) large cell CIS with pleomorphism (57%), in which the cells had abundant
      cytoplasm and nuclear pleomorphism; 2) large cell CIS without nuclear
      pleomorphism (48%); 3) small cell CIS (14%), in which the cytoplasm was
      relatively scant and pleomorphism was usually minimal; 4) clinging CIS (40%), in
      which the urothelium was denuded with a patchy, usually single layer of atypical
      cells; and 5) cancerization of urothelium (16%) with either pagetoid spread
      (clusters or isolated single cells) or undermining or overriding of the normal
      urothelium. Carcinoma in situ with microinvasion into the lamina propria (13
      cases: 3 of 77 CIS cases studied above and 10 additional cases) was evident as
      invasive cells with retraction artifact mimicking vascular invasion (77%, 10
      cases); nests, irregular cords, and strands, or isolated single cells with
      desmoplasia (8%, 1 case); or absent stromal response (15%, 2 cases). Although the
      diagnostic terminology for all of these patterns, for the purposes of the
      surgical pathology report, should be simply urothelial CIS with no specific
      mention of the morphologic pattern, awareness of the histologic diversity of CIS
      will facilitate the diagnosis of this therapeutically and biologically critical
      flat lesion of the urothelium. These lesions may be associated with
      microinvasion, which may be clinically unsuspected and histologically subtle.

PMID- 11224605
TI  - Cutaneous myoepithelioma: an under-recognized cutaneous neoplasm composed of
      myoepithelial cells.
AB  - Benign and malignant neoplasms of myoepithelial cells comprise a rare but well
      characterized group of tumors, among which myoepithelioma of the salivary glands
      is the best known. Extrasalivary examples of myoepithelioma also have been
      described in the breast, larynx, and retroperitoneum. Recently, myoepithelioma of
      the soft tissue also has been reported. According to this description,
      myoepithelioma and mixed tumors arising in the skin and subcutis represent points
      along a clinicopathologic spectrum of cutaneous and soft-tissue tumors. To the
      best of our knowledge, there has been only one case report of an entirely
      cutaneous myoepithelioma in the literature. We report herein five additional
      examples of purely myoepithelial tumors located exclusively in the dermis.
      Histopathologically, the neoplasms were well-circumscribed dermal lesions
      composed of fascicles of spindle cells with eosinophilic cytoplasm and ovoid-to
      spindle-shaped nuclei. Focally, neoplastic aggregations of more epithelioid cells
      representing large round cells with abundant pale cytoplasm arranged in solid
      clusters, cords, or strands were also seen. Ductal differentiation was not
      identified in either of these solid aggregations of epithelioid cells or in the
      fascicles of spindle-shaped cells. Nuclear pleomorphism in epithelioid and
      spindle-cell areas was mild, and mitotic figures were very sparse. In some cases,
      small, necrotic areas were seen within the solid aggregations of spindle-shaped
      cells. Neoplastic stroma was scant and composed of fibrillary collagen and
      abundant mucin. In one case, the stroma consisted of clusters of mature
      adipocytes intermingled with fascicles of myoepithelial cells. Areas of chondroid
      or osteoid metaplasia were not seen in any of the cases. Immunohistochemically,
      neoplastic cells expressed positivity for muscle specific actin (HHF35), alpha
      smooth muscle actin (IA4), S-100 protein, glial fibrillary acidic protein (GFAP),
      and epithelial membrane antigen (EMA), whereas stains for pan-cytokeratin
      (MNF116) were focal and weak. The findings in this report expand the clinical and
      histopathologic spectrum of cutaneous myoepithelioma, an under-recognized
      cutaneous neoplasm of myoepithelial cells.

PMID- 11224607
TI  - Immunoreactivity for thyroid transcription factor-1 in stage I non-small cell
      carcinomas of the lung.
AB  - Thyroid transcription factor-1 (TTF-1) is a nuclear protein regulating the
      transcriptional activity of lung-specific genes in the normal and neoplastic
      bronchioloalveolar cells. It has been implicated in the normal growth and
      development of the lung, and the disruption of the TTF-1 locus leads to neonatal
      death with pulmonary hypoplasia. We evaluated retrospectively the prevalence and
      clinical significance of TTF-1 immunoreactivity in 222 patients with stage I non
      small cell lung carcinoma (NSCLC) with a follow-up time of at least 5 years, and
      we investigated its relationship with other markers of tumor growth, namely cell
      proliferation and angiogenesis. TTF-1 immunoreactivity was documented by using
      the commercially available monoclonal antibody 8G7G3/1 in 72% of 97
      adenocarcinomas, 5% of 119 squamous cell carcinomas, and in the glandular
      component of two adenosquamous carcinomas. Four large cell carcinomas were
      completely unreactive. In adenocarcinomas, but not squamous cell carcinomas, TTF
      1 immunoreactivity correlated significantly with microvessel density (p = 0.04)
      and inversely with the tumor proliferation fraction assessed by Ki-67
      immunostaining (p = 0.03). Also, TTF-1-immunoreactive adenocarcinomas showed a
      trend for a size less than 3 cm (p = 0.08). TTF-1 expression was not related to
      specific growth patterns, tumor grade, or tumor cell typing. TTF-1
      immunoreactivity did not significantly affect patient survival, although patients
      with more than 75% immunoreactive neoplastic cells showed a trend for longer
      overall and disease-free survival. Our findings suggest that TTF-1 could be
      involved in the development of small pulmonary adenocarcinomas, but it has not
      prognostic implications in patients with stage I NSCLC.

PMID- 11224608
TI  - Serous borderline tumor of the paratestis: a report of seven cases.
AB  - We report the clinical, morphologic, immunophenotypic, and ploidy findings of
      seven cases of serous borderline tumor of the paratestis. Mean patient age was 56
      years (range, 14-77 years), and the clinical presentation was that of a
      testicular mass. Tumors ranged in size from 1 to 6 cm (mean, 3.5 cm). Six tumors
      arose from the tunica albuginea, and two of these tumors were intratesticular.
      One tumor arose from the tunica vaginalis. Serous borderline tumor of the
      paratestis is histologically identical to its ovarian counterpart. The tumors
      were cystic with numerous intracystic blunt papillae lined by stratified
      epithelial cells with minimal to mild cytologic atypia. Psammoma bodies were
      present in two cases. In all cases, the neoplastic cells stained strongly and
      diffusely for cytokeratin 7, estrogen receptor, and CD15, and six of seven cases
      were positive for progesterone receptor and MOC-31. The cells did not stain for
      cytokeratin 20, carcinoembryonic antigen, calretinin, and HER2/neu. Proliferative
      activity, as assessed by MIB-1 staining, ranged from 1.3% to 10% (mean, 5.5%).
      Five of six tumors were diploid, and one was tetraploid. Patients were treated by
      radical orchiectomy and followed up from 4 months to 18 years (mean, 48 months;
      median, 8.5 months). No recurrences or metastases occurred. Serous borderline
      tumor of the paratestis is morphologically and immunophenotypically identical to
      ovarian serous borderline tumor. To date, no serous borderline tumor of the
      paratestis reported in the literature or in our series has recurred or
      metastasized after resection.

PMID- 11224609
TI  - Mesonephric adenocarcinomas of the uterine cervix: a study of 11 cases with
      immunohistochemical findings.
AB  - Mesonephric adenocarcinoma is a rare variant of cervical carcinoma with
      relatively few, well-documented cases reported. We describe the clinicopathologic
      and immunohistochemical features of 11 examples of this neoplasm, which occurred
      in women between the ages of 35 and 72 years (mean, 52 years). Most (64%)
      patients had abnormal vaginal bleeding. Eight tumors were stage IB, and one each
      was stage IIB and IVB; in one, the stage was unknown. Microscopically, the
      carcinomas showed various morphologies, most commonly a small tubular pattern or
      a ductal pattern resembling endometrioid adenocarcinoma; one tumor had an
      associated malignant spindle cell component. Ten neoplasms were adjacent to
      hyperplastic mesonephric remnants. Follow-up in 10 cases showed six patients to
      be alive without evidence of recurrence after a mean of 4.8 years. The patients
      with stage IIB and IVB disease had local recurrences after 2.2 and 0.7 years and
      died of progressive disease at 3.2 and 0.8 years, respectively. In a patient with
      stage IB disease, a mediastinal metastasis and a malignant pleural effusion
      developed 5.6 years after diagnosis, and the patient died of disease at 6.2
      years. Another patient with stage IB disease and a positive vaginal cuff margin
      that recurred locally after 1.7 years received chemotherapy and was alive and
      clinically free of disease at 2.5 years. Mesonephric adenocarcinomas were
      immunoreactive for epithelial markers (AE1/3; CK1, CAM 5.2, cytokeratin 7, and
      epithelial membrane antigen) (100%), calretinin (88%), vimentin (70%), androgen
      receptor (33%), and inhibin (30%, focal staining). No immunostaining was detected
      with cytokeratin 20, estrogen receptor, progesterone receptor, and monoclonal
      carcinoembryonic antigen. This staining profile is similar to that of mesonephric
      remnants and may be useful in the distinction of mesonephric carcinoma from
      mullerian endometrioid adenocarcinoma, with which it may be confused.

PMID- 11224610
TI  - Fas ligand expression in Hodgkin lymphoma.
AB  - Because previous investigations suggested involvement of the Fas ligand (FasL) in
      the selection process in the follicular dendritic cell (FDC)-associated cell
      cluster of the germinal center, we investigated the expression of FasL in Hodgkin
      lymphoma (HL) on protein and RNA level, while considering the Epstein-Barr virus
      status of the Hodgkin and Reed-Sternberg (HRS) cells. Tumor tissue from 47
      patients with classic HL (32 nodular sclerosis [NS], 11 mixed cellularity [MC],
      and 4 lymphocyte-rich [LR]) was analyzed by immunohistochemistry for FasL, Fas,
      CD21, and CD23 and by Western blotting for FasL. FasL mRNA was detected by an
      exon 4-specific oligonucleotide and Epstein-Barr virus infection by in situ
      hybridization for Epstein-Barr virus early RNAs (EBER). Western blotting showed
      soluble and membrane-bound forms of FasL. Immunohistochemistry showed FasL
      expression in virtually all HRS of 94% of NS cases and 82% of MC cases. FasL
      expression did not correlate with the Epstein-Barr virus status of the HRS. Low
      FasL protein expression was found in some HRS of LR cases. FasL mRNA was detected
      in 39% of NS, 46% of MC, and 33% of LR cases. Seventy percent to 90% of the HRS
      cells expressed Fas. CD21 immunohistochemistry showed disrupted FDC networks in
      the tumor tissue with reduced and virtually absent expression of CD23 and FasL.
      These observations suggest that FasL expression in HRS cells and the absence of
      FasL in the FDC cluster represent a disturbed microenvironment that may be
      involved in the pathogenesis of HL.

PMID- 11224611
TI  - Peripheral T-cell lymphoma with follicular involvement and a CD4+/bcl-6+
      phenotype.
AB  - A truly follicular pattern is thought to be restricted to B-cell lymphomas. We
      observed a prominent follicular growth pattern in three cases of nodal peripheral
      T-cell lymphomas, of which two were initially diagnosed as follicular lymphomas.
      All three patients were male, ranged in age from 50 to 70 years, and had
      generalized lymphadenopathy at the time of diagnosis. The follicles were sharply
      demarcated in two cases and large and vague in one case; in all cases, they
      contained abundant follicular dendritic cells. Neoplastic cells were small to
      medium, with irregular cleaved or round nuclei and clear cytoplasm, which was
      abundant in one case. Lymphoma cells in all cases were CD4+ CD8- CD57- bcl-6,
      with CD10 coexpression in 2 cases. Clonal rearrangement of the gamma chain of the
      T-cell receptor gene was demonstrated in each case. These cases expand the
      differential diagnosis of lymphomas with a follicular growth pattern and suggest
      that neoplastic T cells may have the capacity to induce or home to follicular
      structures.

PMID- 11224612
TI  - Chordoid glioma of the third ventricle: an ultrastructural study of three cases
      with a histogenetic hypothesis.
AB  - Chordoid glioma is a rare neoplasm occurring in the third ventricle and, as the
      name implies, having a chordoid appearance. It is currently considered a glial
      neoplasm of uncertain histogenesis with distinct clinicopathologic features. We
      report three cases of chordoid glioma with a focus on the ultrastructural
      appearance. The patients were two men and one woman aged, respectively, 34, 40,
      and 43 years. Immunohistochemically, all tumors showed strong and diffuse
      reactivity for glial fibrillary acidic protein and vimentin, whereas
      immunoreactivity for epithelial membrane antigen and cytokeratin was focal.
      Ultrastructurally, they showed features of ependymal differentiation for the
      presence of an apical pole with microvilli and a basal pole characterized, as in
      normal ependyma, by many hemidesmosomelike structures connecting cell membranes
      to the underlying basal lamina. Constant features were a submicroscopic cell body
      zonation (i.e., perinuclear, intermediate, subapical, and apical regions) and the
      presence of secretory granules. These findings were similar to those described
      for the secretory ependymal cells of the subcommissural organ, a small structure
      located in a dorsocaudal region of the third ventricle that undergoes regression
      after birth in humans. Our observations suggest that chordoid glioma may
      represent a subtype of ependymoma whose cells resemble the highly specialized
      ependyma of the subcommissural organ.

PMID- 11224613
TI  - Detection of SYT-SSX fusion gene in peripheral blood from a patient with synovial
      sarcoma.
AB  - This report describes a case involving a 22-year-old pregnant woman with synovial
      sarcoma in the thigh. The patient recognized an elastic hard mass accompanied by
      a dull pain in the anteromedial portion of the right thigh. Magnetic resonance
      imaging delineated a deep soft-tissue mass measuring 9 x 7 x 6 cm. Histologic
      diagnosis of poorly differentiated synovial sarcoma was made based the results of
      an open biopsy. In this patient, the SYT-SSX fusion gene transcript was detected
      by nested polymerase chain reaction (PCR) in the peripheral blood collected
      before biopsy. Two months after wide local resection of the tumor, multiple lung
      metastases developed. This is the first reported case in which tumor cells were
      detected by nested PCR in the peripheral blood of a patient with synovial
      sarcoma. These findings suggest that circulating tumor cells should be monitored
      because they may serve as a prognostic indicator for synovial sarcoma.

PMID- 11224614
TI  - Indolent T-lymphoblastic proliferation: report of a case with an 11-year history
      and association with myasthenia gravis.
AB  - T-lymphoblastic lymphoma is a high-grade malignant lymphoma with frequent
      occurrence in young males, mediastinal involvement, and systemic dissemination.
      Indolent T-lymphoblastic proliferations have rarely been recognized. In the
      present case, we report on an indolent T-lymphoblastic proliferation involving
      the oropharynx in a patient with myasthenia gravis with multiple local
      recurrences over an 11-year period without evidence of systemic dissemination.
      The T-lymphoblasts were consistently positive for terminal deoxynucleotidyl
      transferase (TdT), CD1, CD3, CD4, and CD8, corresponding to an intermediate
      thymocyte stage of differentiation. No cytokeratin-positive thymic epithelial
      cells were identified, ruling out an ectopic thymus or thymoma. T-receptor gene
      rearrangement studies by Southern blot revealed no monoclonal CT-beta
      rearrangement. Indolent T-lymphoblastic proliferations of undetermined clonality
      may rarely occur; predilection for involvement of oropharynx and possible
      association with myasthenia gravis are suggested.

PMID- 11224615
TI  - Survival of patients evaluated by FDG-PET before hepatic resection for metastatic
      colorectal carcinoma: a prospective database study.
AB  - OBJECTIVE: To present the survival results for patients with colorectal carcinoma
      metastases who have undergone liver resection after being staged by [(18)F]
      fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET). SUMMARY
      BACKGROUND DATA: Hepatic resection is standard therapy for colorectal metastases
      confined to the liver, but recurrence is common because of the presence of
      undetected cancer at the time of surgery. FDG-PET is a sensitive diagnostic tool
      that identifies tumors based on the increased uptake of glucose by tumor cells.
      To date, no survival results have been reported for patients who have actually
      had liver resection after being staged by FDG-PET. METHODS: Forty-three patients
      with metastatic colorectal cancer were referred for hepatic resection after
      conventional tumor staging with computed tomography. FDG-PET was performed on all
      patients. Laparotomy was performed on patients not staged out by PET. Resection
      was performed at the time of laparotomy unless extrahepatic disease or
      unresectable hepatic tumors were found. Patients were examined at intervals in
      the preoperative period. RESULTS: FDG-PET identified additional cancer not seen
      on computed tomography in 10 patients. Surgery was contraindicated in six of
      these patients because of the findings on FDG-PET. Laparotomy was performed in 37
      patients. In all but two, liver resection was performed. Median follow-up in the
      35 patients undergoing resection was 24 months. The Kaplan-Meier estimate of
      overall survival at 3 years was 77% and the lower 95% confidence limit of this
      estimate of survival was 60%. This figure is higher than 3-year estimate of
      survival found in previously published series. The 3-year disease-free survival
      rate was 40%. CONCLUSIONS: Preoperative FDG-PET lessens the recurrence rate in
      patients undergoing hepatic resection for colorectal metastases to the liver by
      detection of disease not found on conventional imaging.

PMID- 11224616
TI  - Neoadjuvant therapy of esophageal squamous cell carcinoma: response evaluation by
      positron emission tomography.
AB  - OBJECTIVE: To evaluate the use of positron emission tomography using [(18)F]
      fluorodeoxyglucose (FDG-PET) to assess the response to neoadjuvant radiotherapy
      and chemotherapy in patients with locally advanced esophageal cancer. SUMMARY
      BACKGROUND DATA: Imaging modalities, including endoscopy, endoscopic ultrasound,
      computed tomography, and magnetic resonance imaging, currently used to evaluate
      response to neoadjuvant treatment in esophageal cancer do not reliably
      differentiate between responders and nonresponders. METHODS: Twenty-seven
      patients with histopathologically proven squamous cell carcinoma of the
      esophagus, located at or above the tracheal bifurcation, underwent neoadjuvant
      therapy consisting of external-beam radiotherapy and 5-fluorouracil as a
      continuous infusion. FDG-PET was performed before and 3 weeks after the end of
      radiotherapy and chemotherapy (before surgery). Quantitative measurements of
      tumor FDG uptake were correlated with histopathologic response and patient
      survival. RESULTS: After neoadjuvant therapy, 24 patients underwent surgery.
      Histopathologic evaluation revealed less than 10% viable tumor cells in 13
      patients (responders) and more than 10% viable tumor cells in 11 patients
      (nonresponders). In responders, FDG uptake decreased by 72% +/- 11%; in
      nonresponders, it decreased by only 42% +/- 22%. At a threshold of 52% decrease
      of FDG uptake compared with baseline, sensitivity to detect response was 100%,
      with a corresponding specificity of 55%. The positive and negative predictive
      values were 72% and 100%. Nonresponders to PET scanning had a significantly worse
      survival after resection than responders. CONCLUSION: FDG-PET is a valuable tool
      for the noninvasive assessment of histopathologic tumor response after
      neoadjuvant radiotherapy and chemotherapy.

PMID- 11224617
TI  - Decision analysis for the cost-effective management of recurrent colorectal
      cancer.
AB  - OBJECTIVE: To determine whether the use of [(18)F]2-fluoro-2-deoxyglucose
      positron emission tomography (FDG PET) in addition to computed axial tomography
      (CT) is helpful in managing recurrent colorectal cancer (CRC). SUMMARY BACKGROUND
      DATA: There is no consensus on a management algorithm for CRC. However, when
      recurrence is suspected, CT is generally used for further evaluation and staging
      of disease. METHODS: The authors used decision trees based on theoretical models
      to assess the cost-effectiveness of a CT + FDG PET strategy for the diagnosis and
      management of recurrent CRC compared with a CT-alone strategy. These theoretical
      models focus on patients with hepatic recurrence who are potentially curable
      through surgical hepatic resection. The population entering the decision trees
      consisted of patients with CRC who had undergone surgical resection of their
      primary CRC and who were suspected of having recurrence based on elevated levels
      of carcinoembryonic antigen. RESULTS: The CT + FDG PET strategy was found to be
      cost-effective for managing patients with elevated carcinoembryonic antigen
      levels who were candidates for hepatic resection. The CT + FDG PET strategy was
      higher in mean cost by $429 per patient but resulted in an increase in the mean
      life expectancy of 9.527 days per patient. CONCLUSIONS: These results show,
      through rigorous decision tree analysis, the potential cost-effectiveness of FDG
      PET in the management of recurrent CRC. The decision trees can be used to model
      various features of the management of recurrent CRC, including the cost
      effectiveness of other newly emerging technologies.

PMID- 11224618
TI  - PET scanning in malignancy: infant, adolescent or mature citizen?

PMID- 11224620
TI  - Analysis of reduced death and complication rates after esophageal resection.
AB  - OBJECTIVE: To identify factors that have contributed to reduced rates of death
      and complications after esophageal resection in a 17-year period at a tertiary
      referral center. SUMMARY BACKGROUND DATA: There has been an evolving refinement
      in surgical technique and perioperative management of patients undergoing
      esophageal resection at Queen Mary Hospital during the past two decades. As of
      the end of 1998, there had been no hospital deaths among the last 105 consecutive
      resections performed for esophageal squamous cancer. METHODS: The results of
      esophageal resection for squamous cell carcinoma were analyzed using a
      prospective esophageal database. A longitudinal study was performed to compare
      and analyze rates of death and complications for three consecutive time periods.
      RESULTS: The study group comprised 710 patients who underwent one-stage
      esophageal resection between 1982 and 1998. A transthoracic esophagectomy was the
      preferred approach in 590 patients (83%). The overall hospital death rate was
      11%. The leading causes of hospital death were pulmonary complications (45.5%)
      and progression of malignant disease (21.5%); anastomotic leakage accounted for
      9% of deaths. During the study period, the hospital death rate decreased from 16%
      to 3.2%, and the incidence of postoperative respiratory failure decreased from
      15.5% to 6.5%. Perioperative factors that correlated with the decreased death
      rate over time were the increased postoperative use of epidural analgesia and
      bronchoscopy (for clearance of pulmonary secretions), a decrease in history of
      smoking, and a decrease in surgical blood loss of more than 1,000 mL.
      CONCLUSIONS: In this series of predominantly transthoracic esophagectomies, there
      has been a decline in the hospital death rate to less than 5%. These results are
      largely attributable to factors aimed at reducing postoperative pulmonary
      complications.

PMID- 11224621
TI  - Preoperative characteristics and postoperative behavior of bowel wall on risk of
      recurrence after conservative surgery in Crohn's disease: a prospective study.
AB  - OBJECTIVE: To evaluate in patients with Crohn's disease, using transabdominal
      ultrasound, the morphologic characteristics of the diseased bowel wall before and
      after conservative surgery and to assess whether these characteristics and their
      behavior in the postoperative follow-up are useful and reliable prognostic
      factors of clinical and surgical recurrence. SUMMARY BACKGROUND DATA: Ultrasound
      is effective for evaluating the thickness of bowel wall, the most typical and
      constant finding of Crohn's disease. No data are currently available concerning
      the behavior of the diseased intestinal wall after conservative surgery and
      whether the preoperative characteristics of bowel wall or its behavior after
      conservative surgery may predict recurrence. METHODS: In 85 consecutive patients
      treated with strictureplasty and miniresections for Crohn's disease, clinical and
      ultrasonographic evaluations were performed before and 6 months after surgery.
      Assessed before surgery were the maximum bowel wall thickness, the length of
      bowel wall thickening, the bowel wall echo pattern (homogeneous, stratified, and
      mixed), and the postoperative bowel wall behavior, classified as normalized,
      improved, unchanged, or worsened. RESULTS: A significant correlation was found
      between a long preoperative bowel wall thickening and surgical recurrence. Bowel
      wall thickness after surgery was unchanged or worsened in 43.3% of patients; in
      these patients, there was a high frequency of previous surgery. Patients with
      unchanged or worsened bowel wall thickness had a higher risk of clinical and
      surgical recurrence compared with those with normalized or improved bowel wall
      thickness. CONCLUSION: With the use of abdominal ultrasound, the authors found
      that the thickening of diseased bowel wall may unexpectedly improve after
      conservative surgery, and this is associated with a favorable outcome in terms of
      clinical and surgical recurrence. In addition to its diagnostic usefulness,
      ultrasound also provides reliable prognostic information concerning clinical and
      surgical recurrence in patients with Crohn's disease in the postoperative follow
      up.

PMID- 11224619
TI  - Molecular biology of Barrett's adenocarcinoma.
AB  - OBJECTIVE: To review the current knowledge on the genetic alterations involved in
      the development and progression of Barrett's esophagus-associated neoplastic
      lesions. SUMMARY BACKGROUND DATA: Barrett's esophagus (BE) is a premalignant
      condition in which the normal squamous epithelium of the esophagus is replaced by
      metaplastic columnar epithelium. BE predisposes patients to the development of
      esophageal adenocarcinoma. Endoscopic surveillance can detect esophageal
      adenocarcinomas when they are early and curable, but most of the adenocarcinomas
      are detected at an advanced stage. Despite advances in multimodal therapy, the
      prognosis for invasive esophageal adenocarcinoma is poor. A better understanding
      of the molecular evolution of the Barrett's metaplasia to dysplasia to
      adenocarcinoma sequence may allow improved diagnosis, therapy, and prognosis.
      METHODS: The authors reviewed data from the published literature to address what
      is known about the molecular changes thought to be important in the pathogenesis
      of BE-associated neoplastic lesions. RESULTS: The progression of Barrett's
      metaplasia to adenocarcinoma is associated with several changes in gene
      structure, gene expression, and protein structure. Some of the molecular
      alterations already showed promise as markers for early cancer detection or
      prognostication. Among these, alterations in the p53 and p16 genes and cell cycle
      abnormalities or aneuploidy appear to be the most important and well
      characterized molecular changes. However, the exact sequence of events is not
      known, and probably multiple molecular pathways interact and are involved in the
      progression of BE to adenocarcinoma. CONCLUSIONS: Further research into the
      molecular biology of BE-associated adenocarcinoma will enhance our understanding
      of the genetic events critical for the initiation and progression of Barrett's
      adenocarcinoma, leading to more effective surveillance and treatment.

PMID- 11224622
TI  - Effect of duodenectomy on gastric motility and gastric hormones in dogs.
AB  - OBJECTIVE: To test the hypothesis that the duodenum is required to coordinate
      interdigestive insulin secretion with gastrointestinal motility and to determine
      whether duodenectomy alters the interdigestive cycles of plasma motilin and
      insulin levels and their relations to insulin secretion and motility. METHODS:
      Adult mongrel dogs were chronically implanted with force transducers in the
      stomach, duodenum, and upper jejunum to monitor contractile activity. Eight
      healthy mongrel dogs were divided into control and duodenectomized dogs. Insulin
      secretion, gastrointestinal motility, and plasma concentrations of motilin during
      the interdigestive period were measured in normal and duodenectomized dogs.
      RESULTS: After duodenectomy, no obvious phase III contractions were seen in the
      gastric antrum, but migrating phase III contractions were seen in the upper
      jejunum. The plasma motilin concentration did not fluctuate as it does in normal
      dogs, and remained low. After duodenectomy, insulin secretory cycles were not
      coordinated with either cycles of interdigestive motility or the plasma
      concentration of motilin. Exogenous motilin administration stimulated endogenous
      insulin release significantly compared with saline-treated controls. The
      contractile response of the stomach to exogenous motilin after duodenectomy was
      similar to that of intact dogs. CONCLUSIONS: Duodenectomy disrupts the relation
      between cycles of both interdigestive gastrointestinal motility and insulin
      secretion. These effects of duodenectomy may be attributable to interruption of
      the duodenopancreatic neural connections, hormonal abnormalities, or loss of
      vagus-sensitive humoral factors. The duodenum, which stores motilin, seems to
      play an important role in the relations between gastric migrating motor complexes
      and the concomitant increase of insulin secretion in fasted dogs. The mechanism
      responsible for the effect of motilin in both duodenectomized and normal dogs may
      involve a cholinergic pathway.

PMID- 11224623
TI  - Familial adenomatous polyposis: prevalence of adenomas in the ileal pouch after
      restorative proctocolectomy.
AB  - OBJECTIVES: To determine the prevalence of adenomas in ileal pouches from
      patients with familial adenomatous polyposis (FAP) and to determine whether a
      correlation exists between the presence of pouch adenomas and duodenal adenomas
      and the site of the adenomatous polyposis coli gene mutation. SUMMARY BACKGROUND
      DATA: Restorative proctocolectomy can markedly reduce the risk of colorectal
      adenocarcinoma in FAP patients. However, adenomas with the potential to progress
      to adenocarcinoma can develop in the duodenum, ileum, and continent ileostomy
      after restorative proctocolectomy. More recently, adenomas have been described in
      the ileal pouch after ileoanal anastomosis. METHODS: Pouch endoscopy was offered
      to 167 patients with FAP who had undergone restorative proctocolectomy between
      January 1984 and December 1996. RESULTS: Adenomas were found in 35% of the 85
      ileal pouches examined. No invasive carcinomas were noted. The risk of developing
      one or more adenomas at 5, 10, and 15 years was 7%, 35%, and 75%, respectively.
      Patients with adenomas were more likely to have duodenal and ampullary adenomas.
      No correlation was detected between adenoma development and the site of the
      adenomatous polyposis coli mutation. CONCLUSIONS: Adenomas are frequently found
      in the ileal pouch of patients after restorative proctocolectomy for FAP. Regular
      endoscopic surveillance of the pouch is recommended at a frequency similar to
      that of upper gastrointestinal endoscopy.

PMID- 11224624
TI  - Distributional and functional alterations of immunocompetent peripheral blood
      lymphocytes in patients with chronic pancreatitis.
AB  - OBJECTIVE: To investigate whether the chronic inflammatory process in patients
      with chronic pancreatitis affects their immune function. SUMMARY BACKGROUND DATA:
      Chronic pancreatitis is a chronic inflammatory disease of the exocrine pancreas.
      In approximately 30% of patients, an inflammatory mass of the pancreatic head is
      found, representing an indication for surgery. METHODS: This study comprised 28
      patients with chronic pancreatitis. Sixteen patients were also reevaluated 1 year
      after resection of the pancreatic head for chronic pancreatitis. RESULTS:
      Compared with an age- and gender-matched control group, the number of CD3(+)
      cells was significantly increased in patients with chronic pancreatitis, with an
      increase of both CD3(+)CD4(+) and CD3(+)CD8(+) cells. The number of natural
      killer cells or B lymphocytes did not differ between the patients and the control
      group. After stimulation with phytohemagglutinin or anti-CD3 antibodies, the
      blastogenic response was significantly attenuated in the patients with chronic
      pancreatitis. One year after resection of the pancreatic head for chronic
      pancreatitis, the distribution and the blastogenic response to phytohemagglutinin
      and anti-CD3 antibodies had returned to normal compared with preoperative values.
      CONCLUSION: The chronic inflammatory process in chronic pancreatitis markedly
      affects the distribution and function of peripheral immunocompetent blood cells,
      and elimination of the chronic inflammatory focus by pancreatic head resection
      restores the suppressed immune function in these patients.

PMID- 11224625
TI  - Expression of the adhesion molecules Mac-1 and L-selectin on neutrophils in acute
      pancreatitis is protease- and complement-dependent.
AB  - OBJECTIVE: To examine the effect of pancreatic proteases on the expression of the
      adhesion molecules Mac-1 and l-selectin on neutrophils, and the role of
      complement activation in this process. SUMMARY BACKGROUND DATA: Sequestration of
      neutrophils in the pancreatic and pulmonary microvasculature characterizes acute
      pancreatitis. METHODS: Serum was collected from inbred rats after induction of
      necrotizing pancreatitis; trypsinogen activation peptide was measured to quantify
      trypsin activation. Normal rat serum was also collected and subjected to limited
      trypsin digestion with and without the addition of complement inhibitor. Both
      groups of sera were incubated in vitro with healthy leukocytes. Expression of Mac
      1 and L-selectin on neutrophils was measured quantitatively by flow cytometry. To
      assess the consequences of these events in vivo, trypsinated serum with or
      without complement inhibition or control serum was infused intravenous into rats.
      Soybean trypsin inhibitor was added to serum before injections to block residual
      trypsin activity. Pancreatic and pulmonary injury was quantitated by histology,
      measurement of edema, and myeloperoxidase activity. RESULTS: Mac-1 expression on
      neutrophils incubated with pancreatitis serum was increased compared with
      controls, whereas L-selectin was decreased. Neutrophils incubated with
      trypsinated serum also showed upregulation of Mac-1 and downregulation of L
      selectin, particularly with trypsin at 10(-4) mol/L. Addition of soluble
      complement receptor 1 abrogated both Mac-1 upregulation and L-selectin
      downregulation. Lungs of animals injected with trypsinated serum showed increased
      edema and myeloperoxidase activity, which were reduced by soluble complement
      receptor 1. CONCLUSIONS: Trypsin-generated complement activation participates in
      the upregulation of Mac-1 and shedding of L-selectin on neutrophils in acute
      pancreatitis. Protease or complement inhibition may be effective in preventing
      leukocyte migration and subsequent local and remote organ injury.

PMID- 11224626
TI  - Selection criteria for hepatectomy in patients with hepatocellular carcinoma and
      portal vein tumor thrombus.
AB  - OBJECTIVE: To examine the usefulness of the authors' method involving
      preoperative transcatheter arterial chemoembolization followed by hepatectomy.
      SUMMARY BACKGROUND DATA: The presence of portal vein tumor thrombus in a patient
      with hepatocellular carcinoma is one of the most significant factors for a poor
      prognosis. No standard therapy has been established. METHODS: Forty-five of 455
      patients with hepatocellular carcinoma (10%) from 1989 to 1998 were included in
      this study. These patients had gross portal vein tumor thrombus but no distant
      metastases. The 23 patients (50%) who had indications for surgery received
      preoperative transcatheter arterial chemoembolization: 18 underwent hepatic
      resection and 5 underwent ligation of the hepatic artery or portal vein on
      laparotomy. Among the remaining 22 patients who did not have indications for
      hepatectomy, 10 received regional chemotherapy and 12 underwent transcatheter
      arterial chemoembolization. RESULTS: The mean duration of survival was 3.4 +/-
      2.7 years in the 18 patients who received transcatheter arterial
      chemoembolization and hepatectomy and 0.36 +/- 0.26 years in the 27 patients who
      did not receive hepatectomy. The survival rate of the 18 patients who received
      hepatic resection with preoperative transcatheter arterial chemoembolization was
      82% at 1 year, 42% at 3 years, and 42% at 5 years. Portal trunk occlusion by
      tumor thrombus, three or more primary nodules, an indocyanine green retention
      rate at 15 minutes of 20% or worse, and therapeutic choice other than hepatectomy
      were significant predictors of a poor prognosis on univariate analysis.
      Hepatectomy was the only factor that was significant on multivariate analysis.
      CONCLUSIONS: Patients may enjoy long-term survival if they receive hepatectomy
      with preoperative transcatheter arterial chemoembolization, when the number of
      primary nodules is no more than two, the portal trunk is not occluded by tumor
      thrombus, and the indocyanine green retention rate at 15 minutes is better than
      20%.

PMID- 11224627
TI  - Lymph node metastasis from hilar cholangiocarcinoma: audit of 110 patients who
      underwent regional and paraaortic node dissection.
AB  - OBJECTIVE: To assess the status of the regional and paraaortic lymph nodes in
      hilar cholangiocarcinoma and to clarify the efficacy of systematic extended
      lymphadenectomy. SUMMARY BACKGROUND DATA: There have been no studies in which
      regional and paraaortic lymphadenectomies for hilar cholangiocarcinoma have been
      routinely performed. Therefore, the metastasis rates to the regional and
      paraaortic nodes, the mode of lymphatic spread, and the effect of extended lymph
      node dissection on survival remain unknown. METHODS: This study involved 110
      patients who underwent surgical resection for hilar cholangiocarcinoma with lymph
      node dissection including both the regional and paraaortic nodes. A total of
      2,652 nodes retrieved from the surgical specimens were examined microscopically.
      RESULTS: Of the 110 patients, 52 (47.3%) had no involved nodes, 39 (35.5%) had
      regional lymph node metastases, and 19 (17.3%) had regional and paraaortic node
      metastases. The incidence of positive nodes was significantly higher in the
      patients with pT3 disease than in those with pT2 disease. The pericholedochal
      nodes were most commonly involved (42.7%), followed by the periportal nodes
      (30.9%), the common hepatic nodes (27.3%), and the posterior pancreaticoduodenal
      nodes (14.5%). The celiac and superior mesenteric nodes were rarely involved. The
      3-year and 5-year survival rates were 55.4% and 30.5% for the 52 patients without
      involved nodes, 31.8% and 14.7% for the 39 patients with regional node
      metastases, and 12.3% and 12.3% for the 19 patients with paraaortic node
      metastases, respectively. Of the 19 patients with positive paraaortic nodes, 7
      had no macroscopic evidence of paraaortic disease on intraoperative inspection.
      The survival in this group was significantly better than in the remaining 12
      patients. CONCLUSION: The paraaortic nodes and the regional nodes are frequently
      involved in advanced hilar cholangiocarcinoma. Whether extended lymph node
      dissection provides a survival benefit requires further study. However, the fact
      that long-term survival is possible despite pN2 or pM1 disease encourages the
      authors to perform an aggressive surgical procedure with extended lymph node
      dissection in selected patients with hilar cholangiocarcinoma.

PMID- 11224628
TI  - Arginase I expression and activity in human mononuclear cells after injury.
AB  - OBJECTIVE: To determine the effect of trauma on arginase, an arginine
      metabolizing enzyme, in cells of the immune system in humans. SUMMARY BACKGROUND
      DATA: Arginase, classically considered an enzyme exclusive to the liver, is now
      known to exist in cells of the immune system. Arginase expression is induced in
      these cells by cytokines interleukin (IL) 4, IL-10, and transforming growth
      factor beta, corresponding to a T-helper 2 cytokine profile. In contrast, nitric
      oxide synthase expression is induced by IL-1, tumor necrosis factor, and gamma
      interferon, a T-helper 1 cytokine profile. Trauma is associated with a decrease
      in the production of nitric oxide metabolites and a state of immunosuppression
      characterized by an increase in the production of IL-4, IL-10, and transforming
      growth factor beta. This study tests the hypothesis that trauma increases
      arginase activity and expression in cells of the immune system. METHODS:
      Seventeen severely traumatized patients were prospectively followed up in the
      intensive care unit for 7 days. Twenty volunteers served as controls. Peripheral
      mononuclear cells were isolated and assayed for arginase activity and expression,
      and plasma was collected for evaluation of levels of arginine, citrulline,
      ornithine, nitrogen oxides, and IL-10. RESULTS: Markedly increased mononuclear
      cell arginase activity was observed early after trauma and persisted throughout
      the intensive care unit stay. Increased arginase activity corresponded with
      increased arginase I expression. Increased arginase activity coincided with
      decreased plasma arginine concentration. Plasma arginine and citrulline levels
      were decreased throughout the study period. Ornithine levels decreased early
      after injury but recovered by postinjury day 3. Increased arginase activity
      correlated with the severity of trauma, early alterations in lactate level, and
      increased levels of circulating IL-10. Increased arginase activity was associated
      with an increase in length of stay. Plasma nitric oxide metabolites were
      decreased during this same period. CONCLUSIONS: Markedly altered arginase
      expression and activity in cells of the human immune system after trauma have not
      been reported previously. Increased mononuclear cell arginase may partially
      explain the benefit of arginine supplementation for trauma patients. Arginase,
      rather than nitric oxide synthase, appears to be the dominant route for arginine
      metabolism in immune cells after trauma.

PMID- 11224629
TI  - Use of porcine acellular dermal matrix as a dermal substitute in rats.
AB  - OBJECTIVE: To examine porcine acellular dermal matrix (ADM) as a xenogenic dermal
      substitute in a rat model. SUMMARY BACKGROUND DATA: Acellular dermal matrix has
      been used in the treatment of full-thickness skin injuries as an allogenic dermal
      substitute providing a stable wound base in human and animal studies. METHODS:
      Xenogenic and allogenic ADMs were produced by treating porcine or rat skin with
      Dispase and Triton X-100. Full-thickness skin defects (225 mm2) were created on
      the dorsum of rats (n = 29), porcine or rat ADMs were implanted in them, and
      these were overlain with ultrathin split-thickness skin grafts (STSGs). In two
      adjacent wounds, 0.005- or 0.017-inch-thick autografts were implanted. In other
      experiments, the antimicrobial agent used during ADM processing (azide or a
      mixture of antibiotics) and the orientation of the implanted ADM (papillary or
      reticular side of ADM facing the STSG) were studied. Grafts were evaluated
      grossly and histologically for 30 days after surgery. RESULTS: Significant wound
      contraction was seen at 14, 20, and 30 days after surgery in wounds receiving
      xenogenic ADM, allogenic ADM, and thin STSGs. Contraction of wounds containing
      xenogenic ADM was significantly greater than that of wounds containing allogenic
      ADM at 30 days after surgery. Graft take was poor in wounds containing xenogenic
      ADM and moderately good in those containing allogenic ADM. Wound healing was not
      significantly affected by the antimicrobial agent used during ADM preparation or
      by the ADM orientation. CONCLUSION: Dispase-Triton-treated allogenic ADM was
      useful as a dermal substitute in full-thickness skin defects, but healing with
      xenogenic ADM was poor.

PMID- 11224630
TI  - Prospective randomized trial of two wound management strategies for dirty
      abdominal wounds.
AB  - OBJECTIVE: To determine the optimal method of wound closure for dirty abdominal
      wounds. SUMMARY BACKGROUND DATA: The rate of wound infection for dirty abdominal
      wounds is approximately 40%, but the optimal method of wound closure remains
      controversial. Three randomized studies comparing delayed primary closure (DPC)
      with primary closure (PC) have not conclusively shown any advantage of one method
      over the other in terms of wound infection. METHODS: Fifty-one patients with
      dirty abdominal wounds related to perforated appendicitis, other perforated
      viscus, traumatic injuries more than 4 hours old, or intraabdominal abscesses
      were enrolled. Patients were stratified by cause (appendicitis vs. all other
      causes) and prospectively randomized to one of two wound management strategies:
      E/DPC (wound packed with saline-soaked gauze, evaluated 3 days after surgery for
      closure the next day if appropriate) or PC. In the E/DPC group, wounds that were
      not pristine when examined on postoperative day 3 were not closed and daily
      dressing changes were instituted. Wounds were considered infected if purulence
      discharged from the wound, or possibly infected if signs of inflammation or a
      serous discharge developed. RESULTS: Two patients were withdrawn because they
      died less than 72 hours after surgery. The wound infection rate was greater in
      the PC group than in the E/DPC group. Lengths of hospital stay and hospital
      charges were similar between the two groups. CONCLUSION: A strategy of DPC for
      appropriate dirty abdominal wounds 4 days after surgery produced a decreased
      wound infection rate compared with PC without increasing the length of stay or
      cost.

PMID- 11224631
TI  - A 9-year, single-institution, retrospective review of death rate and prognostic
      factors in adult respiratory distress syndrome.
AB  - OBJECTIVE: To evaluate, at a single institution, the adult respiratory distress
      syndrome (ARDS) death rate in critically ill ventilated surgical/trauma patients
      and to identify the factors predicting death in these patients. SUMMARY
      BACKGROUND DATA: The prognostic features affecting mortality at the onset of ARDS
      have not been clearly defined. Defining rare characteristics would be valuable
      because it would allow for better stratification of patients in clinical trials
      and more appropriate utilization of constrained resources in ICU environments.
      METHODS: A retrospective analysis of 980 ventilated surgical and trauma intensive
      care unit patients from January 1990 to December 1998 was performed at Rhode
      Island Hospital. One hundred eleven adult intensive care unit patients with ARDS
      were identified using the criteria of Lung Injury Score more than 2.50 and the
      definition from the American-European Consensus Conference. Slightly more than
      half were trauma patients, 57% were men, and the median age was 59 years. The
      overall death rate was 52%. Patients were segregated by admission date to the
      intensive care unit (before or after January 1, 1995). Severity of illness was
      measured by the Revised Trauma Score for trauma patients and the Acute Physiology
      and Chronic Health Evaluation III for surgical patients. The Multiple Organ
      Dysfunction Score was determined on the day of onset of ARDS for all patients.
      Other recorded variables were age, sex, intensive care unit length of stay,
      length and mode of ventilation, presence or absence of tracheostomy, ventilation
      variables of peak and mean airway pressures, lung injury scores, elective versus
      emergency surgery, and presence or absence of pneumonia. RESULTS: There was a
      significant decrease in the ARDS death rate from the period 1990 to 1994 to the
      period 1995 to 1998. The major reason for the decline was a reduction in the
      posttraumatic ARDS death rate. Lung-protective ventilation strategies were used
      more frequently in the second period than in the first, and the death rate was
      significantly decreased in trauma patients in the second period when lung
      protective ventilation modes were used. Predictors of death at the onset of ARDS
      were advanced age, Multiple Organ Dysfunction Score of 8 or more, and Lung Injury
      Score of 2.76 or more. CONCLUSION: In this single-institution series, the death
      rate from ARDS declined from 1990 to 1998, primarily in posttraumatic patients,
      and the decrease is related to the use of lung-protective ventilation strategies.
      Based on this patient population, the authors developed a statistical model to
      evaluate important prognostic indicators (advanced age, organ system and
      pulmonary dysfunction measurements) at the onset of ARDS.

PMID- 11224632
TI  - Pancreas resection and islet autotransplantation for end-stage chronic
      pancreatitis.
AB  - OBJECTIVE: To assess the safety and efficacy of islet autotransplantation (IAT)
      combined with total pancreatectomy (TP) to prevent diabetes. SUMMARY BACKGROUND
      DATA: There have been recent concerns regarding the safety of TP and IAT. This is
      thought to be related to the infusion of large volumes of unpurified pancreatic
      digest into the portal vein. Minimizing the volume of islet tissue by purifying
      the pancreatic digest has not been previously evaluated in terms of the
      postoperative rate of death and complications, pain relief, and insulin
      independence. METHOD: During a 54-month period, 24 patients underwent pancreas
      resection with IAT. Islets were isolated using collagenase and a semiautomated
      method of pancreas digestion. Where possible, islets were purified on a density
      gradient and COBE processor. Islets were embolized into the portal vein, within
      the spleen and portal vein, or within the spleen alone. The total median volume
      of digest was 9.9 mL. RESULTS: The median number of islets transplanted was
      140,419 international islet equivalents per kilogram. The median increase in
      portal pressure was 8 mmHg. Early complications included duodenal ischemia, a
      wedge splenic infarct, partial portal vein thrombosis, and splenic vein
      thrombosis. Intraabdominal adhesions were the main source of long-term problems.
      Eight patients developed transient insulin independence. Three patients were
      insulin-independent as of this writing. Patients had significantly decreased
      insulin requirements and glycosylated hemoglobin levels compared with patients
      undergoing TP alone. Of the patients alive and well as of this writing, four had
      failed to gain relief of their abdominal pain and were still opiate-dependent.
      CONCLUSION: Combined TP and IAT can be a safe surgical procedure. Unfortunately,
      almost all patients were still insulin-dependent, but they had decreased daily
      insulin requirements and glycosylated hemoglobin levels compared with patients
      undergoing TP alone. A prospective randomized study is therefore needed to assess
      the long-term benefit of TP and IAT on diabetic complications.

PMID- 11224633
TI  - Randomized trial of choledochocholedochostomy with or without a T tube in
      orthotopic liver transplantation.
AB  - OBJECTIVE: To compare the incidence of biliary complications after liver
      transplantation in patients undergoing choledochocholedochostomy reconstruction
      with or without T tube in a multicenter, prospective, randomized trial. SUMMARY
      BACKGROUND DATA: Several reports have suggested that biliary anastomosis without
      a T tube is a safe method of biliary reconstruction that could avoid
      complications related to the use of T tubes. No large prospective randomized
      trial has so far been published to compare the two techniques. METHODS: One
      hundred eighty recipients of orthotopic liver transplantation were randomly
      assigned to choledochocholedochostomy with (n = 90) or without (n = 90) a T tube
      in six French liver transplantation centers. All types of biliary complications
      were taken into account. RESULTS: The overall biliary complication rate was
      increased in the T-tube group, even though these complications did not lead to an
      increase in surgical or radiologic therapeutic procedures. The major significant
      complication was cholangitis in the T-tube group; this did not occur in the other
      group. The incidence of biliary fistula was 10% in the T-tube group and 2.2% in
      the group without a T tube. Other biliary complications were similar. The
      complication rate of cholangiography performed with the T tube was greater than
      with other types of biliary exploration. The graft and patient survival rates
      were similar in the two groups. CONCLUSION: This study is the first large
      prospective, randomized trial of biliary complications with or without a T tube.
      The authors found an increase in the biliary complication rate in the T-tube
      group, which was linked to minor complications. The T tube did not provide a
      safer access to the biliary tree compared with the others types of biliary
      explorations. The authors recommend the performance of choledochocholedochostomy
      without a T tube in liver transplantation.

PMID- 11224634
TI  - Subcutaneous heparin versus low-molecular-weight heparin as thromboprophylaxis in
      patients undergoing colorectal surgery: results of the canadian colorectal DVT
      prophylaxis trial: a randomized, double-blind trial.
AB  - OBJECTIVE: To compare the effectiveness and safety of low-dose unfractionated
      heparin and a low-molecular-weight heparin as prophylaxis against venous
      thromboembolism after colorectal surgery. METHODS: In a multicenter, double-blind
      trial, patients undergoing resection of part or all of the colon or rectum were
      randomized to receive, by subcutaneous injection, either calcium heparin 5,000
      units every 8 hours or enoxaparin 40 mg once daily (plus two additional saline
      injections). Deep vein thrombosis was assessed by routine bilateral contrast
      venography performed between postoperative day 5 and 9, or earlier if clinically
      suspected. RESULTS: Nine hundred thirty-six randomized patients completed the
      protocol and had an adequate outcome assessment. The venous thromboembolism rates
      were the same in both groups. There were no deaths from pulmonary embolism or
      bleeding complications. Although the proportion of all bleeding events in the
      enoxaparin group was significantly greater than in the low-dose heparin group,
      the rates of major bleeding and reoperation for bleeding were not significantly
      different. CONCLUSIONS: Both heparin 5,000 units subcutaneously every 8 hours and
      enoxaparin 40 mg subcutaneously once daily provide highly effective and safe
      prophylaxis for patients undergoing colorectal surgery. However, given the
      current differences in cost, prophylaxis with low-dose heparin remains the
      preferred method at present.

PMID- 11224636
TI  - The use of radioguided parathyroidectomy in persistent or recurrent
      hyperparathyroidism.

PMID- 11224635
TI  - Impact of increasing comorbidity on infrainguinal reconstruction: a 20-year
      perspective.
AB  - OBJECTIVE: To examine trends in patient and procedural variables and outcomes
      associated with autogenous lower extremity arterial reconstruction (LER) in a
      single center during a period of two decades. SUMMARY BACKGROUND DATA: Surgical
      arterial reconstruction is of proven value in the therapy of patients with
      critical ischemia of the lower extremities. Changing demographics and increasing
      comorbidity are resulting in an increasing prevalence and associated complexity
      of peripheral vascular disease. The effect of these variables on the types and
      outcomes of surgical reconstructions is not known. METHODS: The authors performed
      a retrospective analysis of all autogenous LER procedures performed at their
      institution from 1978 to 1997. Procedures were divided into 5-year intervals:
      group 1, 1978 to 1982; group 2, 1983 to 1987; group 3, 1988 to 1992; group 4,
      1993 to 1997. Categorical parameters were compared using chi-square analysis;
      rates were computed by the life-table method and compared using Mantel-Cox log
      rank analysis. RESULTS: A total of 1,642 autogenous LER procedures were performed
      in 1,274 patients. A significant increase in age, female gender, diabetes
      mellitus, renal failure, and prior coronary artery bypass grafting was noted in
      group 4. Increased technical complexity in this group was reflected by a greater
      incidence of tissue necrosis as the indication for LER, the use of ectopic or
      composite vein, and more distal levels of outflow. The surgical death rate
      remained unchanged (2%) throughout. Patient survival, primary and secondary graft
      patency, and limb salvage at 5 years for the entire cohort were 70 +/- 2%, 63 +/-
      2%, 73 +/- 1%, and 85 +/- 1%, respectively. Hospital length of stay was reduced
      25% from a mean of 15.7 +/- 0.8 days in group 3 to 11.7 +/- 0.4 days in group 4.
      CONCLUSION: In a tertiary practice setting, patients requiring LER present an
      increasingly complex medical and surgical challenge compared with the previous
      decade. Excellent outcomes may still be achieved by an aggressive approach
      relying on autogenous vein conduit.

PMID- 11224637
TI  - Diagnosis and treatment of pediatric viral myocarditis.
AB  - Acute myocarditis is characterized by the rapid development of life-threatening
      congestive heart failure and arrhythmias. Although the initial stages of this
      disorder apparently result from direct cytopathic effects on the atrial and
      ventricular myocardium, later stages of progressive decompensation may result
      from immune-mediated myocyte destruction. There has been recent improvement in
      understanding the role of this immunologic cascade. As a result, treatment now
      begins earlier in the course of the disease and can target both the virus and the
      immune response. Our ability to implement mechanical support in children as a
      bridge to transplant or recovery, even in children presenting in the final stages
      of their disease, has led to an improved outcome regarding morbidity and
      mortality.

PMID- 11224638
TI  - Intravascular and intracardiac stents used in congenital heart disease.
AB  - Intravascular or intracardiac stenoses occur in many forms of congenital heart
      disease or after attempted surgical repair. Although balloon dilation is one
      option for management, restenosis can occur due to elastic recoil immediately
      after the procedure. To address to such stenotic lesions, many reports support
      implanting endovascular stents to provide a framework for vessel expansion. Both
      balloon-expandable fixed tubular mesh stainless steel devices, and self
      expandable stents have had an extensive clinical application. In pediatric
      patients, stents are used for a variety of stenoses, such as systemic venous
      obstruction pathways (eg, Mustard, Fontan baffle, or bidirectional cavopulmonary
      connections), pulmonary artery, right ventricular to pulmonary conduits, aortic
      coarctation, the arterial duct, aorticopulmonary collaterals, or postoperative
      systemic to pulmonary shunts. Because of improvements in device profile,
      implantation rates have increased. Complications such as stent fracture,
      migration, aneurysm formation, and in-stent restenosis occur but only rarely.
      This latter event may be because of intimal hyperplasia and/or continued vessel
      (and patient) growth related to the stent diameter. As such, some instances
      require redilation to manage the acquired lesion. Stent application has
      importantly altered management algorithms in congenital heart disease.

PMID- 11224639
TI  - Dysautonomia and neurocardiogenic syncope.
AB  - Syncope in childhood is a common problem. In most children, syncope is benign,
      secondary to a disturbance in autonomic control of heart rate and blood pressure.
      It is increasingly evident that neurally mediated syncope is a heterogeneous
      group of conditions, necessitating a reclassification of autonomic disorders. New
      entities, such as postural orthostatic tachycardia and cerebral vasoconstrictive
      syncope, are recognized. The key to the diagnosis of syncope is a careful
      history. Tilt testing can be useful when the history is unclear. Unfortunately
      tilt test protocols vary, affecting specificity and sensitivity. The mainstay of
      therapy is reassurance. If symptoms are troublesome, Fludrocortisone and B
      blockers remain the favored drugs. The efficacy of Midodrine and Serotonin Uptake
      Inhibitors is currently under review. Cardiac pacing is effective for those
      patients with severe episodes and demonstrated asystole. It is not known whether
      pacing would be effective for the majority who have neurally mediated syncope
      without significant bradycardia.

PMID- 11224640
TI  - Heart transplantation indicated only in the most severely ill patient:
      perspectives from the German heart transplant experience.
AB  - The COCPIT study, performed in a complete national cohort of adult patients
      consecutively listed for cardiac transplantation in Germany in 1997, found a
      beneficial effect only in the group that was at high risk of dying from heart
      failure without transplantation. If these results can be reproduced in other
      countries, the discussion on the respective roles of pharmacological and organ
      saving surgical therapies for advanced heart failure, medical urgency and waiting
      time as heart transplantation allocation criteria, and the feasibility of a
      randomized clinical trial testing the survival benefit of transplantation must be
      reopened.

PMID- 11224642
TI  - Pathologic markers of allograft arteriopathy: insight into the pathophysiology of
      cardiac allograft chronic rejection.
AB  - Transplant-associated coronary artery disease (CAD) is the principal limiting
      factor for the long-term survival of heart transplant patients. This review
      discusses early risk factors for the subsequent development of transplant
      associated CAD. Early risk factors associated with a prothrombogenic
      microvasculature, such as deposition of microvascular fibrin, depletion of
      vascular tissue plasminogen activator, presence of endothelial activation of the
      allograft arterial tree, and loss of vascular antithrombin, as well as changes in
      circulation (ie, detectable serum cardiac troponin I and elevated serum soluble
      intercellular adhesion molecule-1 levels) are presented and discussed. New
      therapies that could improve the status of the allograft microvasculature and may
      prevent or mitigate the development of transplant-associated CAD are considered.

PMID- 11224641
TI  - The potential role of xenotransplantation in treating endstage cardiac disease: a
      summary of the report of the Xenotransplantation Advisory Committee of the
      International Society for Heart and Lung Transplantation.
AB  - There is an increasing shortage of human donor hearts for transplantation. One
      potential solution is using hearts from a suitable animal source, such as the
      pig. A committee of the International Society for Heart and Lung Transplantation
      has reviewed the current status of research into xenotransplantation.
      Furthermore, the committee considered what results in the pig-to-nonhuman primate
      experimental model would justify a clinical trial of xenotransplantation, and the
      criteria for selecting patients to be entered in the trial. This review
      emphasizes initial patient selection issues, although the committee's overall
      conclusions and recommendations are summarized. Although the current experimental
      results do not presently justify initiating a clinical trial, the committee
      concluded that xenotransplantation theoretically has immense potential, and that
      research in this field should be encouraged and supported. Human cadaveric organ
      donation will still be of the highest priority for the foreseeable future.

PMID- 11224643
TI  - Historical perspectives on cardiac transplantation: the past as prologue to
      challenges for the 21st century.
AB  - The development of cardiac transplantation is based on experimental studies that
      started in the beginning of the last century. The improvement in the surgical
      technique for cardiac transplantation, associated with other progress in the
      field of cardiac surgery and a better understanding of the immune responses,
      allowed cardiac transplantation to become a reality for the treatment of endstage
      heart disease. Recent development in immunosuppressive agents and advances in
      cardiac surgery have meant that cardiac transplantation is not a "fantastic
      speculation for the future," but a reality for the present. Thus, cardiac
      transplantation is performed around the world with an excellent survival rate and
      has become a lifesaving treatment for many patients with severe heart disease.

PMID- 11224644
TI  - Defining "minimally invasive" in valvular heart disease.

PMID- 11224646
TI  - Alternatives in selection of rings for mitral annuloplasty.
AB  - Mitral valve repair with annuloplasty has become a widely accepted technique for
      correction of pathologic lesions of the mitral valve. Advantages over mitral
      valve replacement include improved hemodynamic performance and improved
      ventricular function. The rate of operative mortality in appropriately selected
      patients is low. The success of the mitral valve repair has led to increased
      scrutiny of mitral valve function and a growing realization that rigid rings may
      be detrimental. Flexible rings are increasingly replacing the rigid ring
      traditionally used for annuloplasty, with consequent further improvements in
      ventricular function and cardiac hemodynamics. Other types of rings recently
      introduced include partially flexible rings and adjustable flexible rings. The
      advantages of each are discussed. Relatively new procedures involving shortening
      of the annulus with suture or pericardium show promise.

PMID- 11224645
TI  - Are the indications for tissue valves different in 2001 and how do we communicate
      these changes to our cardiology colleagues?
AB  - The indications for tissue valves in the aortic and mitral positions are becoming
      better defined with advances in valve design, valve preservation, and management
      of reoperations. Although some patients who require cardiac valve replacement
      clearly benefit more from one type of valve than from another, not infrequently
      one encounters a patient who is in the "gray zone," where the optimal choice is
      difficult. At present, bioprostheses for the diseased aortic valve include
      stented porcine and pericardial valves, stentless porcine valves, aortic
      homograft, and pulmonary autograft. For patients with mitral valve disease,
      options for tissue valve replacement are a stented porcine or pericardial
      prosthesis. Generally, factors to consider in choosing the appropriate valve
      substitute include the patient's age, expected life expectancy, coexisting
      medical problems, lifestyle, and socioeconomics; the etiology of the valve
      disease, annular size, and physician and patient preference are also relevant.
      Despite the known finite durability of tissue valves, which is the main
      limitation in their use, the long-term results have been satisfactory,
      particularly in older patients, patients with a limited life expectancy, and
      those undergoing valve replacement in the aortic position. Distillation of
      available information and ongoing communication between the surgeon and the
      cardiologist will enable us to assist the patient in choosing the best valve
      substitute.

PMID- 11224647
TI  - Pitfalls in surgical decision-making during mitral valve repair.
AB  - Mitral valve repair has become the mainstay of surgical treatment for mitral
      valvular regurgitation. Surgeons in North America were relatively slow to adopt
      the various repair techniques, perhaps because rheumatic heart disease was less
      common, and the initial experiences with large numbers of repairs in Europe dealt
      largely with rheumatic disease. Subsequent experience, however, has clearly shown
      that patients with degenerative mitral valve disease can expect very durable
      repairs, and that most such patients have relatively simple pathologic
      conditions. The potential for repair, with a lack of need for long-term
      anticoagulation, has led to earlier surgical intervention. Still, mitral valve
      repair is far more complex than mitral valve replacement and must be accompanied
      by careful intraoperative decision making. Pitfalls exist that are different from
      those that accompany replacement. In this article, we examine some of the more
      common problems, their identification, and, hopefully, ways to avoid them.

PMID- 11224649
TI  - Aortic valve replacement: current clinical practice and opportunities for quality
      improvement.
AB  - This is a review of the current clinical practice and opportunities for quality
      improvement in aortic valve replacement surgery. The topics include trends and
      regional variation in procedure rates, and changes in the use of aortic valve
      replacement among the elderly. Recent developments guiding the choice of
      prosthetic valves and trends in in-hospital mortality rates for aortic valve
      surgery are summarized. Lastly, a discussion of topics relevant to clinical
      practice improvement including the implementation of clinical practice
      guidelines, the need for consensus on risk adjustment, better understanding of
      volume-outcome effects, and the opportunities for comprehensive assessment of
      aortic valve surgery.

PMID- 11224648
TI  - Robotic cardiac valve surgery: transcending the technologic crevasse!
AB  - "The man with a new idea is a crank until the idea succeeds."--Mark Twain. With
      the profound public stress for minimally invasive surgery that guided General
      Surgery, Cardiothoracic Surgery has progressed with warranted enthusiasm. The
      explosion of technological advancements in optics, instrumentation and
      cardiopulmonary bypass has permitted minimally invasive cardiac procedures to be
      performed with safety, efficiency, and efficacy. In this chapter, we review the
      evolution of minimally invasive cardiac valve surgery. The articles of leading
      minimally invasive valve surgeons, both European and American, are reviewed. The
      indications for minimally invasive surgery are explained. Furthermore, the
      present day state of "robotic" mitral valve surgery is described.

PMID- 11224650
TI  - Fats in the new millennium: more complexity but a better understanding?

PMID- 11224651
TI  - Postprandial lipid handling.
AB  - The etiological importance of postprandial lipid metabolism in the development of
      coronary artery disease is now well established. Since then, the work of Patsch
      and others has helped to establish the etiological importance of postprandial
      lipid metabolism in the development of coronary artery disease. Dietary and
      pharmacological interventions have been shown to produce dramatic improvement in
      postprandial lipid handling in high risk groups and have potential to prevent
      coronary artery disease through these effects. Research effort continues to focus
      on the complex mechanisms which underlie defects in postprandial lipid handling,
      with a view to understanding how lifestyle variables such as diet can be modified
      to prevent coronary artery disease.

PMID- 11224652
TI  - Hyperlipidemia and inhibitors of HIV protease.
AB  - HIV protease inhibitors have been successfully incorporated into therapy for
      patients with HIV. These otherwise efficacious treatments present with multiple
      metabolic side-effects and body habitus changes known as the lipodystrophy
      syndrome. Direct associations of the lipid abnormalities with protease inhibitor
      use have been described, and ongoing studies are focused on describing mechanisms
      for future intervention. Mechanisms based on the molecular identity of the
      protease inhibitor target with human proteins, interference with aspects critical
      to lipoprotein production, and interference with adipocyte differentiation have
      been described. This review highlights the complexities of this syndrome, and
      discusses putative mechanisms whereby protease inhibitors cause hyperlipidemia.

PMID- 11224653
TI  - Lipids as modulators of bone remodelling.
AB  - Bone remodelling processes are regulated by systemic hormones and a multitude of
      local and systemic factors, including prostaglandins, cytokines, and growth
      factors. Dietary fatty acids and their derivatives (eicosanoids) have been a
      recent focus of investigation on bone and cartilage metabolism. Specific fatty
      acids are recognized modulators of eicosanoid biosynthesis, signal transduction,
      and gene expression. The actions of polyunsaturated fatty acids have not been
      extensively examined in the skeletal system. Promising research on fatty acids
      and bone remodelling should evaluate the potential effects on pathways for
      osteoclastogenesis and osteoblastogenesis.

PMID- 11224654
TI  - Directed modification instead of normalization of fatty acid patterns in cystic
      fibrosis: an emerging concept.
AB  - Fatty acid patterns divergent from controls have been described in patients with
      cystic fibrosis. The range of this divergence is very broad. In some patients the
      plasma fatty acid pattern is normal, others only have abnormalities of a few
      essential fatty acids, some have fatty acid deviations tending to a reduced
      essential fatty acid status or have overt essential fatty acid deficiency. In the
      past, several nutritional interventions were aimed at normalizing deviating fatty
      acid patterns. Over the years, biochemical findings have been reported that
      suggest that it may be more beneficial to change fatty acid status in a directed
      way rather than normalizing it.

PMID- 11224655
TI  - Polyunsaturated fatty acids and rheumatoid arthritis.
AB  - Rheumatoid arthritis is characterized by infiltration of T lymphocytes,
      macrophages and plasma cells into the synovium, and the initiation of a chronic
      inflammatory state that involves overproduction of proinflammatory cytokines and
      a dysregulated T-helper-1-type response. Eicosanoids synthesized from arachidonic
      acid and cytokines cause progressive destruction of cartilage and bone. The n-6
      polyunsaturated fatty acid gamma-linolenic acid is the precursor of di-homo-gamma
      linolenic acid. The latter and the n-3 polyunsaturated fatty acid
      eicosapentaenoic acid, which is found in fish oil, are able to decrease the
      production of arachidonic acid-derived eicosanoids and to decrease the production
      of proinflammatory cytokines and reactive oxygen species, and the reactivity of
      lymphocytes. A number of double-blind, placebo-controlled trials of gamma
      linolenic acid and fish oil in rheumatoid arthritis have shown significant
      improvements in a variety of clinical outcomes. These fatty acids should be
      included as part of the normal therapeutic approach to rheumatoid arthritis.
      However, it is unclear what the optimal dosage of the fatty acids is, or whether
      there would be extra benefit from using them in combination.

PMID- 11224656
TI  - Long-chain polyunsaturated fatty acids in infant nutrition: effects on infant
      development.
AB  - In the past year, two groups of investigators reported the effects of feeding n-3
      and n-6 long chain polyunsaturated fatty acids on term-infant development. In
      general, these small randomised studies, along with two recent large randomised
      clinical trials, one with preterm and one with term infants, confirm and extend
      data on efficacy from smaller clinical studies reported in the past ten years. In
      addition, two independent systematic reviews published this year evaluated all
      but the most recent studies. Both systematic reviews concluded that there were
      benefits of feeding long chain polyunsaturated fatty acids to preterm infants in
      the short-term and acknowledged the absence of studies to address their effects
      on long-term visual development in infants. The continuing controversy as to the
      need for long chain polyunsaturated fatty acids by term infants is highlighted by
      the different conclusions reached in the systematic reviews. A middle view can
      also be supported by the data; that is, that fewer term infants than preterm
      infants can benefit from these fatty acids because of greater long chain
      polyunsaturated fatty acid accumulation in utero. Differences in intrauterine
      accumulation of these fatty acids may also play a role in inconsistent results
      among term studies.

PMID- 11224657
TI  - Metabolic and nutritional support in critically ill patients: feeding the whole
      body or individual organs?

PMID- 11224658
TI  - Gastrointestinal tract resuscitation in critically ill patients.
AB  - Particular research interest is currently focusing on the resuscitation of the
      gastrointestinal tract, because the gut is regarded to be both the "canary of the
      body", i.e. a sentinel organ during situations of compromised oxygen or substrate
      supply, as well as the "motor of multiple organ failure". Several therapeutic
      strategies have recently been proposed for the resuscitation of this organ
      system, aimed primarily at the augmentation of blood flow and oxygenation but
      also integrating nutritional or metabolic support and antioxidant administration.

PMID- 11224659
TI  - Inter-organ substrate exchanges in the critically ill.
AB  - Metabolic inter-organ exchange is a major field of research for improving the
      treatment of the critically ill. Adapting regional blood flows is the first
      regulatory step, although the relationships between hypoperfusion and metabolic
      disorders are matter of controversy. Metabolic steady state results from a vast
      inter-organ interplay and several nutrients or metabolites are signalling
      molecules in the regulation of gene transcription. Inter- or intra-organ
      substrate recycling shares or delays the mandatory need for aerobic ATP synthesis
      in some conditions. Nitrogen metabolism is highly compartmentalised in an inter
      organ co-operation and liver, muscle, kidney and gut are the most important
      organs. By remodelling the amino acid mixture delivered to peripheral cells after
      intestinal absorption, the liver plays a determinant role in whole body protein
      synthesis. Albumin turnover increases after brain injury. Since the location of
      synthesis is different to that of breakdown this turnover can be viewed as an
      inter-organ exchange. The metabolic side of pH homeostasis is also an inter-organ
      exchange mainly shared by liver, kidney and muscle.

PMID- 11224660
TI  - Dissecting the energy needs of the body.
AB  - The majority of the resting energy expenditure can be explained by the energy
      needs of a few highly metabolic organs, making up a small percentage of the body
      by weight. The relationship of the specific size, individual metabolism, and
      proportional contribution to the actual body weight and total energy expenditure
      for each of these organs is a dynamic process throughout growth and development,
      the onset of disease, and changes in nutritional status. Defining the energy
      needs of the individual tissues and organ systems immeasurably enhances our
      understanding of the body's response to these clinical processes, which otherwise
      could not easily be evaluated by focusing solely on total energy expenditure, fat
      free mass, nitrogen imbalance, or actual body weight. Recently reported studies
      have served mainly to reinforce concepts described previously, and clarify some
      areas of controversy.

PMID- 11224661
TI  - Metabolic changes after cardiac surgery.
AB  - The metabolic changes that occur after cardiac surgery result from a complex
      interaction between the effects of surgery and extracorporeal circulation per se,
      the inflammatory response to surgical trauma and extracorporeal circulation,
      perioperative use of hypothermia, the cardiovascular and neuroendocrine responses
      characteristic to cardiac surgery, and the drugs and blood products used to
      support circulation during and after operation. These changes include among
      others increased oxygen consumption and energy expenditure and increased
      secretion of insulin, growth hormone, adrenocorticotrophic hormone, cortisol,
      epinephrine and norepinephrine. Other changes include decreased total
      Trijodthyronine levels, hyperglycemia, hyperlactatemia, increased glutamate,
      aspartate and free fatty acid concentrations, hypokalemia, an increased
      production of inflammatory cytokines and increased consumption of complement and
      adhesion molecules. There is evidence that better control of metabolic
      abnormalities improves the patients' outcome.

PMID- 11224663
TI  - Effects of serotonin on intestinal secretion and motility.

PMID- 11224662
TI  - Metabolic effects of glucose-insulin infusions: myocardium and whole body.
AB  - In target organs, insulin switches substrate utilization from free fatty acids to
      glucose, a change that: (i) is oxygen-efficient; (ii) repletes glycogen stores;
      (iii) removes potentially toxic fatty acids; and (iv) restores intracellular
      potassium. During or after an ischaemic challenge, the insulin metabolic mode
      should protect cellular functions provided that insulin can reach the ischaemic
      tissue. Insulin, however, also exerts non-metabolic effects, such as membrane
      hyperpolarization, the stimulation of adrenergic activity, and inhibition of
      parasympathetic tone, which may counter its beneficial metabolic actions. The net
      balance between the favourable and unfavourable effects of insulin on ischaemic
      tissues depends on: (i) the dose-response of the various effects; (ii) the
      presence of insulin resistance; (iii) the coexistence of hyperglycaemia; and (iv)
      the stage of ischaemic tissue damage. At present, a role for glucose-insulin
      potassium infusions in clinical practice seems to be clearly established in the
      case of diabetic patients with acute coronary syndromes, and in patients
      undergoing urgent or elective cardiac surgery. Its role as an adjunctive therapy
      in the management of myocardial infarction in non-diabetic individuals has been
      tested in several clinical trials; however, the evidence emerging from them is
      inconclusive.

PMID- 11224664
TI  - Molecular and cellular biology of small-bowel mucosa.
AB  - Study of the molecular and cellular biology of the small-intestinal mucosa is
      providing insights into the remarkable properties of this unique tissue. With its
      structured pattern of cell proliferation, differentiation, and apoptosis, and its
      ability to adapt following exposure to luminal nutrients or injury from surgery
      or pathogens, it functions in a regulated but responsive manner. We review recent
      publications on factors affecting development, gene expression, cell turnover,
      and adaptation.

PMID- 11224665
TI  - Nutrient absorption.
AB  - Some interesting advances in mechanisms and regulation of nutrient absorption
      were reported last year. Further evidence was obtained that the rate-limiting
      step in triacylglycerol absorption, especially with large doses of lipid, is
      transport of prechylomicrons from the endoplasmic reticulum to the Golgi
      apparatus. Targeted disruption of the adenosine triphosphate-binding cassette
      transporter in mice produced changes similar to human Tangier disease and
      suggested that this mouse may be a model for studying intestinal high-density
      lipoprotein assembly and secretion. A new mechanism for carbohydrate
      malabsorption was discovered: in sucrase-isomaltase deficiency, the enzyme fails
      to anchor in the brush border membrane and so is secreted into the lumen, where
      it is ineffective. Glycosylating insulin at B1 phenylalanine permitted it to bind
      to the brush border membrane and greatly enhanced its hypoglycemic activity when
      given orally. CaCo-2 cells and normal human enterocytes were shown to have two
      variants of the human sodium-dependent vitamin C transporter, hSVCT1; one is
      active and the other is an inactive splice variant. In rats, the divalent metal
      ion transporter, DMT1, appeared to be important for regulation of both absorption
      of iron and its movement into the liver.

PMID- 11224667
TI  - Surgery of the small bowel.
AB  - This review deals with various developments in the field of small-bowel surgery,
      including the role of ileal pouch-anal anastomosis and ileorectal anastomosis in
      the treatment of ulcerative colitis and familial adenomatous polyposis. We
      discuss modern trends in the surgical management of Crohn disease, and the
      increasing use of laparoscopy in the management of inflammatory bowel disease and
      small-bowel obstruction. In addition to looking at small-bowel tumors, this
      review deals with the current status of small-bowel transplantation.

PMID- 11224666
TI  - Celiac disease.
AB  - Celiac disease is more prevalent than it was previously thought to be, and
      screening of selected population groups may reveal many new cases. Tissue
      transglutaminase appears to have a significant role in the degradation of gliadin
      and antigen production. Specific gliadin epitopes have been defined using T-cell
      responses. Bone disease is a significant problem for patients with celiac disease
      but management guidelines are being developed. Refractory sprue (nonresponsive
      celiac disease) appears to be a manifestation of enteropathy-associated T-cell
      lymphoma in most cases.

PMID- 11224668
TI  - Recent advances in small-bowel imaging: a review.
AB  - This review outlines technical advances in imaging of the small bowel. These
      include enhancement characteristics of normal bowel mucosa in computed
      tomography, contrast agents in magnetic resonance imaging, contrast
      ultrasonography, small-bowel transit measurements by radionuclide imaging, and
      enteroscopy. Subsequently, the application of these in clinical problem areas,
      including small-bowel obstruction, bleeding, and Crohn and celiac disease, will
      indicate the excellent potential of computed tomography, magnetic resonance
      imaging, and enteroscopy in particular.

PMID- 11224669
TI  - Small-bowel motility.
AB  - Advances in the field of small-bowel motility in the last few years include the
      delineation of the role of the intrinsic primary afferent neuron in eliciting the
      peristaltic reflex, the genetic control of the development of the enteric nervous
      system, and the potential role of the interstitial cells of Cajal as pacemakers
      of the intestine and colon. New promising molecules have been developed for
      therapeutic purposes, particularly in the modulators of serotonin receptors.
      Their effects on sensory and motor function has allowed a better recognition of
      the important role of 5-hydroxytryptamine in several disorders, especially in
      irritable bowel syndrome. In this brief review, we have elected to appraise the
      advances pertaining to human studies, with emphasis on novel methodologies,
      disease manifestations, and novel therapeutic strategies.

PMID- 11224670
TI  - Liver complications and failure in patients on home parenteral nutrition.

PMID- 11224671
TI  - Intravenous nutrition in critical illness.
AB  - Our understanding of the effects of total parenteral nutrition in critical
      illness has been refined over the past year. The importance of not overfeeding
      patients has been highlighted. The effects of lipid emulsions containing medium
      chain triglycerides, compared with standard ones, have been investigated and
      show, in particular, changes in platelet membrane fatty acid composition.
      Although data on clinical end-points are lacking, this is likely to be a fruitful
      area of further research. The importance of providing enteral support, if at all
      possible, has been further underlined by its beneficial effects on bile
      composition in the intensive care setting. Finally, critical illness has been
      shown to be, in general, a contraindication to growth hormone therapy.

PMID- 11224672
TI  - Surgery for obesity.
AB  - As were most types of gastrointestinal surgery, antiobesity surgery was dominated
      by the development of laparoscopic techniques during the last decade. The
      feasibility of performing any primary antiobesity operation safely
      laparoscopically was convincingly demonstrated during the last 2 years. This
      represents a significant continued improvement in the perioperative safety of
      "bariatric" surgery. However, antiobesity surgery entails very much more than
      technique. Unfortunately, little progress has been made in optimizing patient
      selection, improving follow-up, and devising strategies for reoperative
      antiobesity surgery. The latest publications in the field are mainly
      confirmatory, demonstrating durable medically significant weight loss resulting
      in comorbidity reduction with increased life expectancy. The most interesting
      contribution of this surgery is provision of "experimental models" using
      gastrointestinal physiology to study the pathophysiology of obesity and
      undernutrition by guaranteeing substantial weight loss maintained long-term. It
      is unfortunate that surgery for obesity is seriously underutilized.

PMID- 11224673
TI  - Selenium: recent clinical advances.
AB  - Selenium is an essential trace element that serves a number of metabolic
      functions. Its recommended dietary allowance has been set at 55 ug per day for
      adults. Selenium deficiency has not been reported to occur in healthy persons in
      the United States and Canada. However, many people in the world have suboptimal
      intakes of the element and may suffer clinical consequences. Certain viruses
      become more virulent by being passed through selenium-deficient animals. This
      might have public health consequences because viruses of clinical significance
      infect selenium-deficient populations in China and elsewhere. Selenium has also
      been promoted as a cancer chemopreventive agent when given at supranutritional
      levels. Studies are underway to evaluate this use of the element.

PMID- 11224674
TI  - Enteral feeding and Crohn disease.
AB  - Enteral nutrition is an established therapeutic option in the treatment of
      patients with Crohn disease. The mode of action for enteral nutrition remains
      unknown but research efforts have begun to elucidate the complex interaction
      between nutritional luminal contents, intestinal epithelium, and mucosal immune
      response. Trials of novel enteral diet formulations have been conducted to
      explore the antiinflammatory role of specific nutrients.

PMID- 11224675
TI  - Nutrition and the mucosal immune system.
AB  - Gut-associated lymphoid tissue is the dominant site for the initiation of mucosal
      immune response. Mucosal immunity depends on regulatory signals; nutritional
      elements, including fats, amino acids, and micronutrients, are critical cofactors
      for these signals. Nutrients specifically affect lymphocyte influx and migration,
      mononuclear cell activation, and the differentiated expression of immune
      response. The molecular basis of nutrient action has been shown to involve
      effects on receptor regulation, adhesion molecule expression, and the pattern of
      cytokine production. The gastrointestinal mucosal immune system is the major site
      for host interaction with microbes and provides a barrier against systemic access
      for food antigens and microbes. Nutrient metabolism has unique and direct impact
      on the host defense system of gut-associated lymphoid tissue and therefore has
      potential for widely disseminated impact on systemic immune response.

PMID- 11224676
TI  - Intestinal metal ion absorption: an update.
AB  - Recent progress in the field of metal ion transport has significantly advanced
      our understanding of the mechanisms of intestinal metal ion absorption under
      normal and pathological conditions. In this brief review, we focus on the key
      proteins involved in intestinal absorption of iron, zinc, and copper. Following
      the initial description of the apical iron transporter, DCT1, the basolateral
      transporter complex has been identified, which consists of the metal transporter
      IREG1/MTP1 and the multicopper oxidase, hephaestin. Novel zinc and copper
      transporters have been identified as well, mostly based on their homology to
      yeast and plants transporters. The identification of a variety of copper and zinc
      transporters is consistent with the importance of copper and zinc in a wide
      variety of enzymatic reactions, free radical scavenging, and transcriptional
      control.

PMID- 11224677
TI  - Vitamin A: recent advances in the biotransformation, transport, and metabolism of
      retinoids.
AB  - Advances in vitamin A research in 1999 and 2000 have improved the understanding
      the molecular processes through which beta-carotene and other provitamin A
      carotenoids are converted to vitamin A, the roles of cellular retinoid-binding
      proteins that serve as retinoid chaperones during metabolism, the regulation of
      retinoid transport, and the nature and regulation of several enzymes required for
      the absorption, storage, activation, and inactivation or degradation of
      retinoids. Not only has a clearer picture emerged of specific molecular
      processes, but it is also becoming evident that whole-body retinoid homeostasis
      is facilitated by close communication among organs due to the rapid interorgan
      recirculation of retinoids, and by the "autoregulation" by retinoic acid of
      several enzymes and retinoid-binding proteins that mediate retinoid homeostasis.

PMID- 11224678
TI  - New insights into paroxysmal nocturnal hemoglobinuria.
AB  - The characteristic, defining defect in paroxysmal nocturnal hemoglobinuria is the
      somatic mutation of the PIG-A gene (essential to the biosynthesis of the
      glycosylphosphatidylinositol moiety that affixes a number of proteins to the
      cellular surface) in hematopoietic cells. These cells thus lack the proteins
      usually held in place by this anchor. The absence of these proteins is the most
      reliable diagnostic criterion of the disease and is responsible for many of the
      clinical manifestations of PNH. The current hypothesis explaining the disorder
      suggests that there are two components: (1) hematopoietic stem cells with the
      characteristic defect are present in the marrow of many if not all normal
      individuals in very small numbers; (2) some aplastogenic influence suppresses the
      normal stem cells but does not suppress the defective stem cells, thus allowing
      the proportion of these cells to increase. Current research attempts to
      substantiate this hypothesis and design therapy consistent with the hypothesis.
      Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired stem cell disorder
      characterized by intravascular hemolysis, hypercoagulability, and relative bone
      marrow failure [1]. It is characterized by a somatic mutation in the gene
      encoding the alpha1-6-N-acetylglucosaminyltransferase necessary for the formation
      of the glycosylphosphatidylinositol (GPI) anchor that binds certain proteins to
      the membrane surface (Fig. 1) [2,3*]. Whereas many of the manifestations can be
      accounted for by the absence of these proteins on the cells of the hematopoietic
      system, it is not entirely clear whether this defect is sufficient to make the
      disease manifest. In this paper, the author reviews recent clinical observations
      and relates them to the underlying pathophysiology of the disease.

PMID- 11224679
TI  - Autoimmune disorders of erythropoiesis.
AB  - Immune-mediated disorders of erythropoiesis can result in acquired severe anemia,
      low reticulocyte counts, and bone marrow exhibiting pure red cell aplasia or
      ineffective erythropoiesis. Erythropoiesis can be suppressed or impaired by
      humoral or cellular mechanisms. In vitro inhibition of erythroid colony growth by
      immunoglobulins or lymphocytes can be a strong argument for the immune origin of
      the disease. Classical etiologies are thymoma and hematologic malignancies such
      as chronic lymphocytic leukemia (CLL). Clonal proliferation of T cells has been
      incriminated. Recently, acquired circulating autoantibodies directed against
      erythropoietin have been detected in a case of pure red cell aplasia. Autoimmune
      mechanisms have also been detected or suggested in synartesis and in Fas
      associated dyserythropoiesis, two distinct syndromes recently described where
      morphologic abnormalities specific to the erythroid lineage illustrate
      ineffective erythropoiesis.

PMID- 11224680
TI  - Regulation of alternative pre-mRNA splicing during erythroid differentiation.
AB  - Although the mature enucleated erythrocyte is no longer active in nuclear
      processes such as pre-mRNA splicing, the function of many of its major structural
      proteins is dependent on alternative splicing choices made during the earlier
      stages of erythropoiesis. These splicing decisions fundamentally regulate many
      aspects of protein structure and function by governing the inclusion or exclusion
      of exons that encode protein interaction domains, regulatory signals, or
      translation initiation or termination sites. Alternative splicing events may be
      partially or entirely erythroid-specific, ie, distinct from the splicing patterns
      imposed on the same transcripts in nonerythroid cells. Moreover, differentiation
      stage-specific splicing "switches" may alter the structure and function of
      erythroid proteins in physiologically important ways as the cell is
      morphologically and functionally remodeled during normal differentiation.
      Derangements in the splicing of individual mutated pre-mRNAs can produce
      synthesis of truncated or unstable proteins that are responsible for numerous
      erythrocyte disorders. This review will summarize the salient features of
      regulated alternative splicing in general, review existing information concerning
      the widespread extent of alternative splicing among erythroid genes, and describe
      recent studies that are beginning to uncover the mechanisms that regulate an
      erythroid splicing switch in the protein 4.1R gene.

PMID- 11224681
TI  - Regulation of red cell membrane protein interactions: implications for red cell
      function.
AB  - This article presents new insights into the molecular mechanism for regulating
      red cell membrane protein interactions that are responsible for erythrocyte
      membrane mechanical properties. For various skeletal proteins, structure-function
      correlations of protein 4.1R have been studied in detail. Kinetic analysis with
      the resonant mirror detection method has determined the nature of 4.1R
      interactions with various binding partners such as band 3, glycophorin C, and
      p55, and their binding sites. More importantly, calmodulin (CaM) binds to 4.1R in
      a Ca2+-independent manner to modulate the 4.1R interactions in the presence of
      Ca2+ at microM. Crystal structure of the 30-kD domain of 4.1R has a cloverleaf
      like architecture with three lobes, each of which contains a binding region
      specific for binding partners. CaM binds to the grooves situated in two regions
      between the three lobes, possibly leading to conformational changes of the three
      lobes with a consequent alteration in the capacity of 4.1R to bind to its
      partners. The present findings on erythrocyte 4.1R should provide a basis for
      better understanding the membrane functions of nonerythroid cells.

PMID- 11224682
TI  - Molecular insights into receptors used by malaria parasites for erythrocyte
      invasion.
AB  - The invasion of erythrocytes by malaria parasites is a multi-step process that
      requires a series of highly specific molecular interactions. Here, the authors
      review what has been learned about receptor-ligand interactions that mediate
      erythrocyte invasion. Parasite proteins involved in these interactions are
      promising candidates for malaria vaccines. Clear understanding of these
      interactions is important for the rational design of vaccines that attempt to
      inhibit invasion and prevent malaria.

PMID- 11224683
TI  - Erythrocytic vacuolar rafts induced by malaria parasites.
AB  - Studies in the past year displaced long-standing dogmas and provided many new
      molecular insights into how proteins and solutes move between the erythrocyte
      plasma membrane and the malarial vacuole. Highlights include a demonstration that
      (1) detergent-resistant membrane (DRM) rafts exist in the red cell membrane and
      their resident proteins are detected as rafts in the plasmodial vacuole, (2) a
      voltage-gated channel in the infected red cell membrane mediates uptake of
      extracellular nutrient solutes, and (3) intraerythrocytic membranes transport a
      parasite-encoded adherence antigen to the red cell surface.

PMID- 11224684
TI  - What's new in hemochromatosis.
AB  - Hereditary hemochromatosis (HHC) is an inherited disorder of iron metabolism
      affecting approximately 1 in 200-300 individuals of Northern European descent.
      Over time, the continued deposition of iron in parenchymal cells of many organs
      can eventually lead to diabetes mellitus, cardiomyopathy, and hepatic cirrhosis,
      the last of which is frequently followed by hepatocellular carcinoma. Although
      the complications of HHC can be devastating, its clinical management is simple
      and effective if the disease is identified early in its progression. The recent
      elucidation of the HFE gene has provided insight into the pathogenesis of HHC and
      provided a means for the early identification of individuals in whom HHC may
      develop. Two mutations have been implicated in HHC: C282Y and H63D. The former
      occurs in a homozygous state seen in 75-100% of patients with HHC. The high
      correlation of HFE to HHC has caused it to be considered as a candidate gene for
      population-based genetic testing for diagnosis and detection of predisposition to
      HHC. In addition, mechanisms of iron transport and metabolism are unfolding and
      are providing clues to the enigma of iron homeostasis and the pathophysiology of
      iron overload.

PMID- 11224685
TI  - Pleiotropic and epistatic effects in sickle cell anemia.
AB  - Sickle cell anemia is the first monogenic disease ever described, and it became
      the paradigm for a disease traceable to a single mutation in a single gene.
      Pauling's concept of "molecular disease," based on this discovery, opened a new
      chapter in the history of medicine. Nevertheless, at the phenotypic level, sickle
      cell anemia is not a monogenic disease; it is a multigenic disease. The latter is
      the product of pleiotropic genes (involved in secondary pathophysiologic events)
      and epistatic genes (same gene but with significant pathophysiologic consequences
      among individual=polymorphism). These secondary events are an important part of
      the phenotype and explain the intense interindividual differences in the severity
      of the disease, in spite of all the patients having the same sickle globin gene
      in the homozygote form. In the last decade a number of epistatic genes and
      pleiotropic genes have been defined, and many others are potential candidates.
      CHIP technology and high-throughput sequencing promise to accelerate our full
      multigenic understanding of this disease, contributing to a more individualized
      concept of disease in conjunction as we enter the new millennium.

PMID- 11224686
TI  - Acute chest syndrome of sickle cell disease: new light on an old problem.
AB  - The pulmonary findings of acute chest syndrome of sickle cell disease have been
      well characterized in numerous studies. Whereas a third of patients have a
      documented infection associated with this syndrome, and fat embolism from
      necrotic marrow is the etiologic factor in another approximately 10%, no cause is
      discovered in the majority of patients. In most patients, however, the underlying
      pathophysiology is the presence of a hypoxia-driven, adhesion-related occlusive
      event in the pulmonary microcirculation. This may be accompanied by a decrease in
      the levels of normal cytoprotective and anti-adhesive mediators such as nitric
      oxide. In the patient with sickle cell disease, the lung is also a uniquely
      vulnerable target organ because its vasculature constricts with hypoxia in
      contrast to other vascular beds. This review will establish the links between
      known etiologic agents and the pathophysiology of this syndrome. An additional
      section of this review will deal with experimental therapies. The use of inhaled
      nitric oxide will be explored in depth because advances in this area are current
      and uniquely relevant to acute chest syndrome.

PMID- 11224688
TI  - Nonsteroidal anti-inflammatory drugs and the kidney.

PMID- 11224687
TI  - Pharmacologic induction of fetal hemoglobin: raising the therapeutic bar in
      sickle cell disease.
AB  - The favorable effects of high levels of fetal hemoglobin (Hb F) in sickle cell
      disease have been recognized for several decades. This has been an important
      incentive for the development of therapeutic agents that increase Hb F
      production. 5-Azacytidine, the first such agent in clinical use, was proposed
      based on a molecular understanding of the role of DNA methylation in globin gene
      regulation. Controversy over the mechanism of Hb F induction by 5-azacytidine led
      to the identification of hydroxyurea as another agent that can increase Hb F
      production. Although the clinical benefit of hydroxyurea has been demonstrated in
      a randomized clinical trial, greater increases in Hb F are clearly needed for
      optimal therapeutic effect. Butyrates also increase Hb F levels, and their use in
      combination with hydroxyurea appears to be synergistic. Now that multiple
      therapeutic agents are available for Hb F induction, the use of combination
      therapy to increase Hb F levels sufficiently to prevent all the complications of
      sickle cell disease has become a realistic goal.

PMID- 11224689
TI  - Hypertension and the failing kidney.

PMID- 11224690
TI  - Ischemic nephropathy.
AB  - Ischemic nephropathy is a major cause of chronic renal failure in people over 50
      years of age. In addition, renal artery stenosis is associated with increased
      mortality, particularly if renal or cardiac function is compromised. The
      diagnosis is made both by clinical characteristics and imaging studies. At
      present, duplex Doppler ultrasound and magnetic resonance angiography appear to
      be the most promising non-invasive screening tests. Although data from controlled
      trials are lacking, revascularization is the mainstay of therapy for ischemic
      nephropathy. Advances in percutaneous interventions now allow revascularization
      to be offered to many patients, including those who are poor surgical candidates.
      The role of medical therapies (statins, angiotensin-converting enzyme inhibitors,
      intensive control of blood pressure) and how to best utilize revascularization
      (which patients and when) remain to be defined.

PMID- 11224691
TI  - Antiphospholipid antibody syndrome and renal disease.
AB  - The antiphospholipid syndrome is a disorder of hypercoagulability in association
      with circulating antiphospholipid antibodies directed against epitopes on
      oxidized phospholipids complexed with a glycoprotein, beta 2-glycoprotein I, or
      against the glycoprotein itself. Disorders associated with antiphospholipid
      antibodies but not the antiphospholipid syndrome, such as HIV and hepatitis C
      infection, appear to lack antibodies to beta 2-glycoprotein I. Patients with
      systemic lupus erythematosus have a high incidence of antiphospholipid antibodies
      with a high risk of thrombosis, often associated with anticardiolipin antibodies,
      beta 2-glyocoprotein I antibodies, and the presence of the lupus anticoagulant.
      Antiphospholipid antibodies are a significant cause of morbidity and mortality in
      renal patients with and without systemic lupus erythematosus. Renal
      manifestations include thrombotic microangiopathy and large vessel thrombosis. In
      patients with end-stage renal disease, antiphospholipid antibodies are prevalent
      and may increase in frequency with time on dialysis, possibly as a result of
      oxidative stress incurred during dialysis. The presence of anticardiolipin
      antibodies have been associated with a high incidence of hemodialysis access
      clotting. In renal transplant recipients, the incidence of antiphospholipid
      antibodies is also elevated and may be associated with a higher incidence of
      primary graft non-function. Although patients with systemic lupus erythematosus
      have similar renal allograft survival rates to the general population, survival
      is worse for those patients who are also antiphospholipid antibody positive.
      Additionally, in hepatitis C positive renal transplant recipients, the presence
      of anticardiolipin antibodies confers an increased risk of thrombotic
      complications and the development of thrombotic microangiopathy. Treatment of
      antiphospholipid antibody syndrome remains centered around anticoagulation with
      warfarin. The use of immunosuppressive agents has had no dramatic effect on
      antiphospholipid antibody titers and little clinical effect on thrombotic events.

PMID- 11224692
TI  - Familial focal segmental glomerulosclerosis.
AB  - There is increasing recognition of the importance of genetic factors in the
      development of focal segmental glomerulosclerosis and related proteinuric
      disorders. Recently, four genes have been identified which, when defective, cause
      focal segmental glomerulosclerosis or nephrosis. All of these genes appear to be
      important in the maintenance of glomerular podocyte function. However, not all
      cases of familial nephrosis or proteinuria are explained by defects in these
      genes.

PMID- 11224693
TI  - Treatment of focal segmental glomerulosclerosis.
AB  - The prognosis of untreated patients with focal segmental glomerulosclerosis is
      poor, as the disease progress to end-stage renal disease in approximately 50--70%
      of nephrotic patients. Although focal segmental glomerulosclerosis was initially
      considered to be a steroid-resistant disease, several studies have shown a better
      responsiveness to more prolonged courses of steroids. For patients with steroid
      resistant or -dependent focal segmental glomerulosclerosis, cyclosporine A and
      cytotoxic agents have shown efficacy in clinical trials. Plasmapheresis or LDL
      apheresis may represent a rescue treatment in patients who do not respond to
      other therapies. The role of other agents used in focal segmental
      glomerulosclerosis, including azathioprine, mycophenolate mofetil, tacrolimus,
      pefloxacin or vitamin E is still poorly defined.

PMID- 11224694
TI  - Dyslipidemia and renal disease: pathogenesis and clinical consequences.
AB  - Patients with chronic renal disease suffer from a secondary form of complex
      dyslipidemia. The most important abnormalities are an increase in serum
      triglyceride levels (elevated VLDL-remnants/IDL), small LDL particles and a low
      HDL cholesterol level. The highly atherogenic LDL subclass, namely LDL-6 or small
      dense LDL, accumulates preferentially in hypertriglyceridemic diabetic patients
      with nephropathy or on hemodialysis treatment. All these lipoprotein particles
      contain apolipoprotein B, thus the complex disorder can be summarized as an
      elevation of triglyceride-rich apolipoprotein B-containing complex lipoprotein
      particles. Growing evidence suggests that all of the components of this type of
      dyslipidemia are independently atherogenic. These particles, specifically the
      apolipoprotein B moiety, are predominantly prone to modification such as
      oxidation and glycosilation, which contributes to impaired clearance by the LDL
      receptor. These complex alterations in lipoprotein composition not only passively
      accompany chronic renal disease but on the contrary also promote its progression
      and the development of atherosclerosis. Therefore, renal patients with
      dyslipidemia should be subjected to lipid-lowering therapy. The effectiveness of
      lipid lowering on the reduction of cardiovascular endpoints or the progression of
      renal disease is under investigation or remains to be studied.

PMID- 11224695
TI  - Prevention of nephrolithiasis.
AB  - The high incidence of recurrence after an initial stone event underscores the
      need for an effective medical prophylactic program. Dietary modification and drug
      therapies have long been advocated to reduce the likelihood of stone recurrence.
      While the efficacy of a high fluid intake has been validated in a randomized
      trial, the benefit of other dietary measures is based on modulation of urinary
      stone risk factors and outcomes derived from observational studies. Several drug
      therapies have been evaluated in a limited number of prospective, randomized
      trials and efficacy has been demonstrated for thiazides, allopurinol and alkali
      citrate in some populations of recurrent stone formers. The role of selective
      versus nonselective therapy for stone prevention awaits further study.

PMID- 11224696
TI  - Novel therapies for anti-neutrophil cytoplasmic antibody-associated vasculitis.
AB  - High-dose corticosteroids in combination with cytotoxic drugs are universally
      accepted as the initial approach in vasculitides that are associated with anti
      neutrophil cytoplasmic antibodies. Cyclophosphamide is the most effective
      cytotoxic drug and is used in more severe cases. Because cyclophosphamide has
      more severe short- and long-term side-effects than methotrexate, methotrexate is
      used in less severe cases. New prospects for the treatment of vasculitis include
      novel immunosuppressive agents (e.g. mycophenolate, 15-deoxyspergualin, and
      leflunomide), sequential chemotherapy (e.g. cyclophosphamide followed by
      azathioprine or cyclophosphamide followed by methotrexate), intravenous
      immunoglobulin, tumour necrosis factor-alpha directed therapy, anti-lymphocyte
      directed therapy (e.g. antithymocyte globulin or anti CD52/anti CD4 antibodies),
      anti-adhesion molecule directed therapy (e.g. anti-CD18 or intercellular adhesion
      molecule-1 antisense) or immunoablation using high-dose cytotoxic medication with
      or without stem cell rescue.

PMID- 11224697
TI  - Gender and the progression of renal disease.
AB  - Many studies of chronic renal disease have reported that men have a more rapid
      progression of renal insufficiency. However, other studies have found no
      differences between the sexes, and the true effect of sex on chronic renal
      disease remains a topic of controversy. There is evidence that women with non
      diabetic renal diseases experience a slower progression, but in diabetic renal
      disease, the effect of gender is not yet established. Sex hormones may mediate
      the effects of gender on chronic renal disease, through alterations in the renin-
      angiotensin system, reduction in mesangial collagen synthesis, the modification
      of collagen degradation, and upregulation of nitric oxide synthesis.

PMID- 11224698
TI  - Non-genomic actions of aldosterone: role in hypertension.
AB  - There is universal acceptance of the existence of rapid, non-genomic effects of
      aldosterone, although their physiological relevance and potential importance in
      hypertension are not yet clear. What has emerged over the year under review is
      that at least some of such rapid non-genomic effects of aldosterone may be
      mediated by the activation of the classical intracellular mineralocorticoid
      receptor, rather than a putative membrane receptor. The post-receptor mechanisms
      of rapid aldosterone action appear variously to involve protein kinase C,
      calcium, cyclic adenosine 3', 5'-monophosphate and inositol 1, 4, 5-triphosphate,
      with downstream effects on a variety of ion pumps and channels.

PMID- 11224699
TI  - 20-hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids and blood pressure.
AB  - The properties of 20-hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids,
      vasoactivity and modulation of ion transport and mediation/modulation of the
      effects of vasoactive hormones, such as angiotensin II and endothelin, underscore
      their importance to renal vascular mechanisms and electrolyte excretion. 20
      Hydroxyeicosatetraenoic acid is an integral component of renal autoregulation and
      tubuloglomerular feedback as well as cerebral autoregulation, eliciting
      vasoconstriction by the inhibition of potassium channels. Nitric oxide inhibits
      20-hydroxyeicosatetraenoic acid formation, the removal of which contributes to
      the vasodilator effect of nitric oxide. In contrast, epoxyeicosatrienoic acids
      are generally vasodilatory by activating potassium channels and have been
      proposed as endothelium-derived hyperpolarizing factors. 20
      Hydroxyeicosatetraenoic acid modulates ion transport in key nephron segments by
      influencing the activities of sodium--potassium-ATPase and the sodium--potassium-
      chloride co-transporter; however, the primacy of the various arachidonate
      oxygenases that generate products affecting these activities changes with age.
      The range and diversity of activity of 20-hydroxyeicosatetraenoic acid is
      influenced by its metabolism by cyclooxygenase to products affecting vasomotion
      and salt/water excretion. 20-Hydroxyeicosatetraenoic acid is the principal renal
      eicosanoid that interacts with several hormonal systems that are central to blood
      pressure regulation. This article reviews the most recent studies that address 20
      hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids in vascular and renal
      tubular function and hypertension.

PMID- 11224700
TI  - Angiotensin II type 2 receptors: signalling and pathophysiological role.
AB  - The signalling mechanisms and biological significance of the angiotensin II type
      2 receptor have long been unknown. In recent years, studies, first in cell
      culture models but now increasingly also in vivo, have shed some light on the
      molecular events occurring after a stimulation of the receptor with its ligand as
      well as on its physiological effects and its significance for pathophysiological
      processes. There is increasing evidence that the angiotensin II type 2 receptor
      is involved in different pathophysiological processes, such as myocardial
      infarction, heart and kidney failure, and stroke.

PMID- 11224701
TI  - Oxidative stress and vascular damage in hypertension.
AB  - Oxidative stress, a state of excessive reactive oxidative species activity, is
      associated with vascular disease states such as hypertension. In this review, we
      discuss the recent advances in the field of reactive oxidative species-mediated
      vascular damage in hypertension. These include the identification of redox
      sensitive tyrosine kinases, the characterization of enzymatic sources of
      superoxide production in human blood vessels, and their relationship with
      vascular damage in atherosclerosis and hypertension. Finally, recent developments
      in the search for strategies to attenuate vascular oxidative stress are reviewed.

PMID- 11224702
TI  - Systolic blood pressure, pulse pressure and arterial stiffness as cardiovascular
      risk factors.
AB  - For many years systolic and diastolic blood pressure were the exclusive
      mechanical factors predicting cardiovascular risk in populations of normotensive
      and hypertensive individuals. However, if hypertension acts as a mechanical
      factor with deleterious consequences on the arterial wall, the totality of the
      blood pressure curve should be considered to evaluate the risk. The purpose of
      this review is to show that, in addition to systolic and diastolic blood
      pressure, other haemodynamic indexes with particular relevance for cardiac
      complications and that originate from pulsatile pressure should be taken into
      account, namely brachial pulse pressure and aortic pulse wave velocity. The main
      recent findings in normotensive and hypertensive populations are: (i) increased
      pulse pressure is an independent predictor of myocardial infarction, congestive
      heart failure and cardiovascular death, even in hypertensive patients undergoing
      successful antihypertensive drug therapy; (ii) increased aortic pulse wave
      velocity and increased carotid incremental elastic modulus are also both
      independent predictors of cardiovascular mortality, mainly in patients with end
      stage renal disease and, to a lesser extent, in individuals with essential
      hypertension. Currently, increased pulse pressure and increased pulse wave
      velocity may be considered either as simple markers of an underlying vascular
      disease or as strong cardiovascular risk factors. The solution of this important
      question requires the development of specific intervention trials.

PMID- 11224703
TI  - Antihypertensive drug therapy in older patients.
AB  - Elevated pulse pressure is an important cardiovascular risk factor in the
      elderly, and it remains to be determined whether this can be reversed. Drug
      treatment is justified in older patients with isolated systolic hypertension
      whose systolic blood pressure is 160 mmHg or higher on repeated measurement.
      Absolute benefit is greater in men, in patients aged 70 years or more, and in
      those with previous cardiovascular complications or greater pulse pressure. In
      the recently published comparative trials blood pressure gradients largely
      accounted for most, if not all, of the differences in outcome. In hypertensive
      patients, calcium-channel blockers may offer greater protection against stroke
      than against myocardial infarction, resulting in an overall cardiovascular
      benefit similar to that provided by older drug classes. The hypothesis that
      angiotensin-converting enzyme inhibitors or alpha-blockers might influence
      outcome over and beyond that expected on the basis of their blood pressure
      lowering effects still remains to be proved.

PMID- 11224704
TI  - Bone marrow transplantation in sickle cell anemia.
AB  - Hematopoietic cell transplantation (HCT) is a treatment with curative potential
      for sickle cell disease (SCD). The experience of HCT for persons with beta
      thalassemia major has been successfully extended to SCD. Currently, the event
      free survival rate after allogeneic-matched sibling HCT for SCD is 82%. However,
      short-term and long-term transplant-related complications remain substantial
      barriers to HCT, particularly in older patients with life-long complications of
      SCD. Novel conditioning regimens that minimize transplant-associated toxicity
      have been developed and show promise for wider application of HCT. Alternative
      stem cell sources may also expand the availability of HCT for selected patients
      with SCD.

PMID- 11224705
TI  - Biology and management of idiopathic myelofibrosis.
AB  - Idiopathic myelofibrosis (IMF) is a hematopoietic stem cell disorder
      characterized by hypercellularity of the bone marrow with an increase in abnormal
      megakaryocytes, varying degrees of marrow fibrosis, and extramedullary
      hematopoiesis. The central lesion of the IMF stem cell is not known; however, the
      marrow fibrosis is a polyclonal reaction to inflammatory mediators generated by
      the transformed clone. Historical management approaches have centered on
      improving the patient's blood counts in a palliative manner. Recent reports of
      autologous and allogeneic bone marrow transplantation (BMT) in IMF patients
      indicate that stable engraftment occurs easily, the marrow fibrosis is a
      reversible process, and a graft-versus-fibrosis effect may exist. The goals of
      future therapies will target marrow fibrosis and harness the graft-versus
      fibrosis effect to safely and effectively treat patients with IMF.

PMID- 11224706
TI  - Nonmyeloablative hematopoietic cell transplantation.
AB  - The myeloablative doses of chemotherapy and radiation used with conventional
      allogeneic hematopoietic cell transplantation produce considerable morbidity and
      mortality that generally limit this treatment to patients younger than 55 years
      of age and in good general medical condition. It has become clear that T-cell
      mediated graft-versus-tumor effects play an important role in the elimination of
      malignant disease after allotransplants. Several investigators have sought to
      reduce regimen-related toxicities while optimizing graft-versus-tumor effects.
      Strategies can be broadly categorized as reduced-intensity regimens that retain
      some toxicities and require hospitalization, and minimally myelosuppressive
      regimens that rely on immunosuppression for allogeneic engraftment and resultant
      graft-versus-tumor effects. The latter approach can be performed in the
      ambulatory care setting. Preliminary results are encouraging. If long-term
      efficacy is demonstrated, such strategies would expand treatment options for
      patients who would otherwise be excluded from receiving conventional allografts.

PMID- 11224707
TI  - Predictive molecular markers in non-small cell lung cancer.
AB  - Recent biotechnologic knowledge has enabled the discovery of a cornucopia of
      genetic abnormalities commonly involved not only in cancer but also in other
      diseases ranging from the plague to arteriosclerosis. The wealth of possibilities
      uncovered by this knowledge inspires the hope that today's dream of a unified
      concept of common treatment for multiple diseases could become a future reality.
      This review arbitrarily categorizes recent findings into five major areas. First,
      cisplatin resistance associated with the nucleotide excision repair pathway can
      help clinical oncologists to choose between cisplatin and noncisplatin
      combinations. Second, the relevant role of nuclear factor-kappa B as a predictor
      of chemosensitivity can lead to the development of new drugs abrogating nuclear
      factor-kappa B expression. Third, the presence of tubulin mutations, which are
      directly involved in resistance to microtubule-interactive drugs, can guide
      chemotherapy based on taxane or nontaxane combinations. In addition, certain
      chromosomal deletions affect genes involved in deoxyribonucleotide synthesis,
      like ribonucleotide reductase, that intervene in gemcitabine metabolism; this
      raises interest in investigating deletion at chromosome 11p15.5 as a potential
      mechanism of gemcitabine resistance. Finally, an overwhelming number of
      publications have analyzed genes involved in cell cycle regulation and
      development as predictive markers of survival; however, where these pieces fit
      into the puzzle of cancer management is still unclear.

PMID- 11224708
TI  - Optimizing chemoradiation therapy approaches to unresectable stage III non--small
      cell lung cancer.
AB  - There have been important recent advances in the management of inoperable non-
      small cell lung cancer. Concurrent cisplatinum-or carboplatin-based chemotherapy
      and 60 to 64 Gy of thoracic radiation therapy has replaced sequential therapy as
      the new standard therapy for good-risk patients. New agents such as docetaxel,
      gemcitabine, and irinotecan are being tested to replace the standard chemotherapy
      given during thoracic radiation. Phase II studies of induction or consolidation
      chemotherapy have also shown promise but these agents have not yet been proven to
      improve outcome in a prospective randomized study. New strategies for optimizing
      thoracic radiation, primarily by dose escalation with three-dimensional conformal
      technique, have also led to an improved therapeutic ratio. Alternative strategies
      may be required for poor-risk, elderly patients.

PMID- 11224709
TI  - Role of cadherins and matrixins in melanoma.
AB  - Cancer is generally viewed as the result of disrupted intra-and intercellular
      homeostatic regulation. Once the homeostatic balance is lost and malignant
      transformation has occurred, microenvironmental factors such as degradation of
      matrix components and host-tumor interactions are essential for survival and
      growth of malignant cells. Within the previous year, cadherins and matrixins
      (matrix metalloproteinases) have emerged as key factors in these processes. The
      pathways involved are interconnected and detailed knowledge about the biologic
      significance of each member in a given pathway is essential for our understanding
      of oncogenesis. Restoration of E-cadherin-mediated control over melanoma cells
      and modulation of the involved regulation pathways are promising novel
      therapeutic strategies. Another approach is the rational design of inhibitors
      that perturb matrix metalloproteinases in a particular cell type and interrupt
      tumor-specific proteinase activation cascades. Advances in these fields will lead
      to the development of better tools for prevention, diagnosis, and therapy.

PMID- 11224710
TI  - Novel immunologic approaches to the management of malignant melanoma.
AB  - In the past decade, the discovery of tumor antigens recognized by T cells has
      revolutionized the tumor vaccine field. The appreciation that peptides are bound
      to and restricted by major histocompatibility class I and II molecules for immune
      recognition has encouraged a number of early-phase clinical trials of peptide
      vaccines. I summarize herein the rationale for and the results of a number of
      clinical trials of peptide vaccines for melanoma, suggesting that immune and
      clinical responses can be seen in those with metastatic and resected disease
      using a variety of surrogate assays. The challenge for the future is to correlate
      the results of immunologic assays with clinical benefit in patients with advanced
      cancer.

PMID- 11224711
TI  - Update on genetic events in the pathogenesis of melanoma.
AB  - Melanoma is the most common fatal malignancy among young adults, and its
      incidence and mortality continue to increase at an alarming rate. Epidemiologic
      studies have clearly demonstrated roles for genetic predisposition and sun
      exposure in melanoma development. In the past few years, substantial information
      has been added to the body of evidence suggesting that inherited and somatic
      genetic events contribute to the pathogenesis of melanoma. This review focuses on
      recent advances in the understanding of the genetic events, particularly
      aberration of cell cycle control and transcriptional control mechanisms,
      implicated in the pathogenesis of melanoma.

PMID- 11224713
TI  - Update on topical carbonic anhydrase inhibitors.
AB  - Topical carbonic anhydrase inhibitors are a novel addition to the armamentarium
      of medical glaucoma treatment; dorzolamide has been available since 1995 and
      brinzolamide since 1998. They lower intraocular pressure by inhibiting carbonic
      anhydrase, a key enzyme for aqueous humor formation. Intraocular pressure
      lowering activity of the substances appears to be the same and is similar to that
      of most other agents, but it does not reach the activity of the unselective beta
      blocker timolol or the prostaglandin latanoprost. On concomitant treatment,
      additivity is reached with all other topical agents. A possible improvement of
      blood flow may offer an additional benefit, but its significance for the long
      term outcome for human glaucoma remains to be shown. Side effects are mostly
      local. A more physiologic pH of brinzolamide appears to be advantageous.

PMID- 11224714
TI  - Role of tissue growth factors in aqueous humor homeostasis.
AB  - The aqueous humor supplies nutrients to the nonvascularized cornea, lens, and
      trabecular meshwork. A number of tissue growth factors have been detected in this
      fluid. The composition of these proteins changes dramatically with different
      ocular conditions, such as inflammation and glaucoma. In this review, an overview
      of new findings regarding effects of aqueous humor growth factors is given. Our
      main emphasis is on the regulation of the avascular anterior eye compartment, the
      possible role of growth factors in the pathogenesis of glaucoma, and the
      importance of growth factors for the special immunosuppressive status of the
      anterior chamber.

PMID- 11224715
TI  - The diagnostic value of optic nerve imaging in early glaucoma.
AB  - In the last decade, new imaging techniques have been added to conventional fundus
      photography and have been evaluated for use in early glaucoma. They all measure
      the loss of neuroretinal rim or retinal nerve fiber layer as a correlate to
      glaucomatous ganglion cell and axon loss. The value of optic disc photography,
      planimetry, laser scanning tomography, laser scanning polarimetry, and optical
      coherence tomography for the diagnosis of glaucomatous eyes in a preperimetric or
      early perimetric stage is analyzed on the basis of sensitivity, specificity, and
      receiver operating characteristics (ROC) curves. It becomes clear that all these
      techniques allow a more or less semi-automated evaluation of the optic disc and
      retinal nerve fiber layer but still have their limitations in the diagnosis of a
      very early, preperimetric stage of the glaucoma disease.

PMID- 11224716
TI  - Screening models for glaucoma.
AB  - For social and economic reasons, glaucoma screening is a useful and necessary
      task, with possible benefits for individuals and the health care system arising
      from the early diagnosis and early therapy of patients with glaucoma. Early
      treatment of patients with glaucoma decreases the probability that those patients
      will become blind and lowers the direct and indirect costs for patients with
      glaucoma. Most of the reported studies dealing with glaucoma screening used only
      one parameter (eg, intraocular pressure) to detect and to discriminate glaucoma
      patients from healthy subjects. Glaucoma screening devices might be combined to
      obtain the best specificity and sensitivity. Because the diagnosis of glaucoma is
      very closely associated with a morphologic change in the optic nerve head, one
      screening parameter should be the morphology of the papilla. To increase
      specificity and sensitivity, a combination of morphologic and functional testing
      might be useful. In this review, we report the context of glaucoma screening in
      terms of health economics, the testing quality of devices for functional and
      morphologic screening, and the results of a pilot study.

PMID- 11224717
TI  - The iris after prostanoid treatment.
AB  - Morphologic studies to date show that prostanoid-induced iris color change is not
      associated with any major pathologic process in the tissue. There is no evidence
      of melanocyte proliferation. The most likely mechanism for iris color darkening
      is increased melanogenesis, but this is not so marked as to cause any extensive
      release of melanin granules that might cause iris inflammation or even a
      pigmentary-type of glaucoma. Some patients, but not all, with color darkening
      have an apparent thickening of the anterior border zone; it remains to be
      established whether this is true thickening or merely if the anterior border is
      emphasized because of increased pigmentation.

PMID- 11224718
TI  - What is on the horizon for cycloablation?
AB  - The concept of cycloablation has been present for several decades, but the
      inability to titrate a predictable and reproducible response has been its
      drawback. However, cycloablation still plays an important role in our paradigm of
      glaucoma therapy, since it can be the treatment of last resort for a small group
      of patients who have exhausted all other treatment modalities. Experience with
      argon or diode endolaser cyclophotocoagulation holds promise for these and other
      patients because it appears to demonstrate a safer side-effect profile, while
      providing good results. Better results may be partially due to visualization of
      the ciliary processes before applying laser energy, which allows for targeted
      destruction of tissue and limits the amount of inflammation. Additional
      experience will better define the indications and scope of these newer
      modalities.

PMID- 11224719
TI  - Exfoliation syndrome.
AB  - Exfoliation syndrome (XFS) is an age-related disorder of the extracellular matrix
      characterized by production and progressive accumulation of small, white deposits
      of a fibrillar extracellular material in many ocular tissues, most commonly seen
      on the pupillary border and anterior lens capsule. Characteristic signs of
      pigment liberation and deposition throughout the anterior segment aid in the
      diagnosis. Exfoliation syndrome predisposes to both open-angle and angle-closure
      glaucoma, and to capsular rupture, zonular dehiscence, and vitreous loss during
      cataract extraction. Exfoliation syndrome is associated with ocular and perhaps
      systemic ischemia. The exact chemical composition of exfoliation material remains
      unknown. Medical, laser, and surgical therapy are similar to treatment of primary
      open-angle glaucoma.

PMID- 11224720
TI  - The impact of glaucoma medication on parameters of ocular perfusion.
AB  - Whereas intraocular pressure is considered a major risk factor in glaucoma,
      growing evidence now indicates that ocular ischemia plays a major role too. By
      virtue of this and because many existing medications are able to interact with
      vasculature, altering ocular blood flow, it is essential that current and future
      medications for glaucoma be evaluated for their effect on ocular circulation. The
      authors review published papers examining the effect of topical and some systemic
      medications on ocular blood flow, focusing mostly on data from the human eye. The
      authors provide a comprehensive review on the effect of subclasses of medications
      (eg, carbonic anhydrase inhibitors, beta-blockers, alpha-adrenergic agonists, and
      prostaglandin analogues on optic nerve head, and on retinal, choroidal, and
      retrobulbar circulation. The various claims for enhancements or reduction of
      ocular circulation within each class of medication are reviewed and evaluated.

PMID- 11224721
TI  - The value of polarimetry in the evaluation of the optic nerve in glaucoma.
AB  - Scanning laser polarimetry (SLP) is a technology used to measure the thickness of
      the human retinal nerve fiber layer (NFL) in vivo. SLP has been demonstrated to
      well differentiate between glaucomatous, ocular hypertensive, and normal eyes,
      despite overlapping data. Recently increased interest is seen in the polarizing
      properties of the cornea and crystalline lens that may lead to spurious
      measurements. Although the instruments that use SLP compensate for these anterior
      segment polarizing properties, recent interest has focused on the extent and
      effects of incomplete compensation. If well compensated in all, SLP may better
      separate diseased from normal eyes. Its promising role in the follow-up of
      glaucoma is still under investigation.

PMID- 11224722
TI  - Modulation of wound healing after glaucoma surgery.
AB  - The healing process after glaucoma filtration is the main determinant of surgical
      failure and, even more important, the final intraocular pressure. The ability to
      fully control wound healing may ultimately give us the ability to set the
      intraocular pressure in the low teens for all patients undergoing glaucoma
      filtration surgery. The authors review the changes in how to use antimetabolites
      to improve safety, and many of the exciting new areas of progress, including
      growth factor neutralization and future molecular therapies to control wound
      healing.

PMID- 11224723
TI  - The pros and cons of different prostanoids in the medical management of glaucoma.
AB  - The prostaglandin analogs are new exciting drugs added to the therapeutic
      armamentarium for patients with glaucoma. Several studies have evaluated the
      ocular hypotensive properties and side effects of latanoprost in different forms
      of glaucoma. This drug, seems to be the most effective intraocular pressure (IOP)
      reducing agent currently available, and has a low incidence of ocular and
      systemic side effects. Fewer data are available regarding unoprostone, but the
      IOP-reducing effect of this drug seems to be comparable or slightly inferior to
      that of timolol and it produces fewer side effects. When compared with
      unoprostone, latanoprost has been shown to effect a greater reduction in IOP. A
      major drawback to the use of prostaglandin analogues is the lack of long-term
      experience such as that currently available for other classes of agents.

PMID- 11224724
TI  - Airway effects of marijuana, cocaine, and other inhaled illicit agents.
AB  - Several substances besides tobacco are inhaled for recreational purposes,
      including marijuana, crack cocaine, amyl and butyl nitrites, heroin,
      methamphetamine, and phencyclidine. Abuse of most of these inhaled substances has
      risen in recent years, thereby increasing concern about potential pulmonary and
      other medical complications. Regular marijuana use can lead to extensive airway
      injury and alterations in the structure and function of alveolar macrophages,
      potentially predisposing to pulmonary infection and respiratory cancer. Crack
      cocaine use can lead to a variety of acute pulmonary complications, including
      severe exacerbations of asthma and an acute lung injury syndrome associated with
      a broad spectrum of histopathologic changes ("crack lung"). Habitual cocaine
      smoking may also produce more subtle long-term pulmonary consequences due to
      chronic alveolar epithelial and microvascular lung injury. Heroin inhalation can
      induce severe and even fatal exacerbations of asthma. Pulmonary consequences of
      inhaled amyl and butyl nitrites, crystalline methamphetamine (ice), and
      phencyclidine have been less well documented.

PMID- 11224725
TI  - New combination therapies for asthma.
AB  - Combination products often have useful clinical benefits in asthma. The
      scientific rationale for combination therapy includes the fact that different
      agents have complimentary modes of action. Long-acting beta(2)-agonists have
      effects on airway smooth muscle, and inhaled corticosteroids have potent topical
      antiinflammatory effect. This combination has been shown to effectively reduce
      exacerbations and improve symptoms. Substantial clinical trial data provide a
      rationale for dual-control therapy supported by basic scientific data. Another
      combined therapy is inhaled steroids plus leukotriene-receptor antagonists, which
      provides the patient with two effective therapies. Leukotriene-receptor
      antagonist can also be combined with antihistamines for improved asthma control.
      Older therapies including theophylline and controlled release albuterol have been
      effectively added to inhaled corticosteroids, enabling a reduction in the dose of
      the inhaled steroids. Many other combination therapies are presently being
      tested.

PMID- 11224726
TI  - beta(2)-Adrenergic receptor polymorphisms and asthma.
AB  - The idea that an abnormality in the beta(2)-adrenergic receptor contributes to
      asthma has been a long-standing hypothesis. Since the discovery of functionally
      relevant polymorphisms in the beta(2)-adrenergic receptor gene, there has been
      intensive research on their impact on asthma and related phenotypes, particularly
      the responsiveness to bronchodilators. It is the aim of this chapter to summarize
      the latest developments in this interesting field of research.

PMID- 11224727
TI  - Role of corticosteroids in acute exacerbations of chronic obstructive pulmonary
      disease.
AB  - Systemic corticosteroid therapy for patients with exacerbations of chronic
      obstructive pulmonary disease has become increasingly commonplace over the past
      two decades. This practice was controversial because a number of small clinical
      trials provided inconclusive evidence about efficacy. Experience from recent
      trials indicates that systemic cortico-steroids are modestly effective in this
      setting. Systemic corticosteroids administered to hospitalized patients reduces
      the absolute treatment rate by about 10%, increases the forced expiratory volume
      in 1 second (FEV(1)) by about 100 mL, and shortens the hospital stay by 1 to 2
      days. Treatment should not extend longer than 2 weeks. The optimal starting dose
      is not known. Hyperglycemia and possibly an increased rate of secondary
      infections are expected complications of treatment.

PMID- 11224728
TI  - Role of corticosteroids in stable chronic obstructive pulmonary disease.
AB  - Evidence supporting or refuting the use of corticosteroids in the treatment of
      patients with chronic obstructive pulmonary disease (COPD) has only recently
      become available, and evidence is still missing for a number of important
      clinical issues. Results from four large studies on the long-term effects of
      inhaled corticosteroids on COPD and other controlled studies on the more short
      term effects of inhaled corticosteroids provide evidence that regular treatment
      with these drugs is only appropriate for a limited group of patients with COPD.
      These include symptomatic COPD patients with documented spirometric response to
      inhaled corticosteroids or those with a forced expiratory volume in 1 second
      (FEV(1)) less than 50% predicted and repeated exacerbations requiring treatments
      with antibiotics or oral corticosteroids.

PMID- 11224729
TI  - Extrapulmonary effects of chronic obstructive pulmonary disease.
AB  - Although airflow obstruction is the most obvious and most studied manifestation
      of chronic obstructive pulmonary disease (COPD), it should not be overlooked that
      COPD, particularly in its later stages, is associated with many extrapulmonary
      features that contribute to the morbidity, reduced quality of life, and,
      possibly, mortality of this disease. We review here the literature on skeletal
      muscle dysfunction, osteoporosis, and weight loss in COPD, with particular
      attention to possible approaches to their management. Patients with COPD may also
      have other extrapulmonary effects such as hormonal abnormalities that could
      probably be corrected, but less is known about them. COPD, therefore, should be
      regarded as a systemic disorder. Its systemic manifestations should not be
      overlooked in the overall care of the patient, because there are important ways
      in which they can be addressed.

PMID- 11224730
TI  - Surgery for chronic obstructive pulmonary disease: the place for lung volume
      reduction and transplantation.
AB  - Lung volume reduction surgery and lung transplantation have been shown to improve
      lung function, exercise capacity, and quality of life in patients with advanced
      emphysema. Because the indications for both surgical procedures overlap, lung
      volume reduction surgery may be used as an alternative treatment or as a "bridge"
      to lung transplantation. In this article, we discuss patient selection, clinical
      outcome parameters, and the morbidity and mortality associated with each surgical
      procedure. We focus on the different preoperative predictors of good and poor
      outcomes after lung volume reduction surgery, the role of pulmonary
      rehabilitation, and the preferred surgical techniques for lung volume reduction
      surgery. An overview of the postoperative care of emphysema patients who undergo
      single-lung transplantation is also discussed.

PMID- 11224731
TI  - Sleep in patients with asthma and chronic obstructive pulmonary disease.
AB  - Sleep abnormalities are common in patients with asthma and chronic obstructive
      pulmonary disease. Recent studies have provided new insight into the mechanisms
      involved in circadian changes in airway resistance, analyzed the effect of
      disease treatment on sleep quality, and re-examined issues relating to oxygen
      supplementation at night in patients with chronic obstructive pulmonary disease.
      Although providing new and useful information, some of these studies also raise
      new questions that will need answering in the future. This article reviews our
      current understanding of the complex interactions between sleep and lung disease
      in patients with asthma and chronic obstructive pulmonary disease.

PMID- 11224732
TI  - Update on work disability in rheumatic diseases.
AB  - Two recent studies suggest the prevalence of rheumatic condition-related work
      disability is considerably lower than was suggested in previous studies. However,
      the samples in the recent studies did not include older workers and included
      persons who gained employment after disease onset. In other recent studies, the
      rate of work disability among persons employed at disease onset is still high; a
      fair amount of work disability occurs in the early years of disease. There is no
      clear evidence yet that treatment improvements have altered the rates of work
      disability. Because work characteristics, like level of physical demand,
      influence risk for work disability and are potentially amenable, other
      interventions are needed to reduce rheumatic disease-associated work disability.
      Accommodation provided to alleviate problems in doing work and outside of work
      activities is the most promising intervention, followed by job/career change.
      Assessment tools are just now becoming available to help clinicians identify
      patients in need of assistance.

PMID- 11224733
TI  - Evaluating the quality of care in rheumatic diseases.
AB  - An understanding of the level of health care quality and the factors that affect
      it is necessary for providers and insurers to optimize health outcomes for
      patients and should be carefully considered when making decisions about resource
      allocation. Additionally, information about health care quality can be used by
      patients and others to inform decisions about the purchase of health care.
      Although much work has been done to characterize the quality of health care,
      little is known about the quality of care for the rheumatic diseases. This paper
      reviews what is known about health care quality for these diseases.

PMID- 11224734
TI  - Epidemiology and impact of rheumatic disorders in the United States Hispanic
      population.
AB  - The emergence of a sizable Hispanic population in the US is a relatively recent
      historical phenomenon, and thus much is still unknown about this group of North
      Americans. Data from national surveys suggest small differences between Hispanic
      and non-Hispanic white populations in the age-adjusted prevalence of self
      reported arthritic conditions. However, the rate of activity-limitation
      attributable to arthritis is higher among Hispanic patients. This likely reflects
      the poorer socioeconomic conditions and lack of health insurance that prevail
      among Hispanic populations, which may limit their access to rheumatologic care.
      Osteoporotic vertebral and hip fractures are less frequent, and proximal femoral
      mineral density is higher, in Hispanic individuals than in non-Hispanic white
      individuals. The mechanisms for these observations are currently under
      investigation. There have been no studies of the prevalence of osteoarthritis,
      rheumatoid arthritis, or systemic lupus erythematosus among Hispanic populations.
      However, important immunogenetic, clinical, and psychosocial differences between
      Hispanic and non-Hispanic patients in regard to rheumatoid arthritis and systemic
      lupus erythematosus have been reported. There is no published information on the
      prevalence or characteristics of other rheumatic diseases in the US Hispanic
      population. Emerging evidence suggests considerable underuse of certain health
      services for arthritis among Hispanic patients, likely due in part to
      socioeconomic factors. Further research is needed to determine whether biologic,
      cultural or psychosocial factors contribute to underuse as well. There is clearly
      a need for data on the prevalence and characteristics of arthritis and other
      rheumatic and musculoskeletal diseases in this emerging US population.

PMID- 11224735
TI  - Genetic epidemiology of primary osteoarthritis.
AB  - Primary osteoarthritis (OA) is a late onset disease that fits most accurately
      into the oligogenic, multifactorial class of genetic diseases. Twin pair and
      family risk studies have highlighted a surprisingly large genetic component to OA
      and have prompted the search for predisposing genes. These searches have taken
      three forms: (1) parametric linkage analysis of rare families in which OA
      segregates as a Mendelian trait, (2) model-free linkage analysis of affected
      sibling pairs, and (3) association analysis of known candidate genes. Within the
      past year linkage analysis studies have highlighted that chromosomes 2, 4, 6, 7,
      11, 16, and the X may each harbor an OA susceptibility gene. Chromosomes 2, 4,
      and 16 were identified in multiple genome scans and are therefore the most likely
      to encode susceptibility. Association analysis of candidates suggests that the
      syntenic genes for type II collagen and the vitamin D receptor (12q12--q13.1) may
      also encode for OA susceptibility.

PMID- 11224736
TI  - Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome.
AB  - The prevalence of chronic widespread pain in the general population in Israel was
      comparable with reports from the USA, UK, and Canada. Comorbidity with
      fibromyalgia (FM) resulted in somatic hyperalgesia in patients with irritable
      bowel syndrome. One sixth of the subjects with chronic widespread pain in the
      general population were also found to have a mental disorder. Mechanisms involved
      in referred pain, temporal summation, muscle hyperalgesia, and muscle pain at
      rest were attenuated by the N-methyl-D-aspartate (NMDA) antagonist, ketamine, in
      FM patients. Delayed corticotropin release, after interleukin-6 administration,
      in FM was shown to be consistent with a defect in hypothalamic corticotropin
      releasing hormone neural function. The basal autonomic state of FM patients was
      characterized by increased sympathetic and decreased parasympathetic systems
      tones. The severity of functional impairment as assessed by the Medical Outcome
      Survey Short Form (SF-36) discriminated between patients with widespread pain
      alone and FM patients. Chronic fatigue syndrome (CFS) occurred in about 0.42% of
      a random community-based sample of 28,673 adults in Chicago, Illinois. A
      significant clinical overlap between CFS and FM was reported. Cytokine
      dysregulation was not found to be a singular or dominant factor in the
      pathogenesis of CFS. A favorable outcome of CFS in children was reported; two
      thirds recovered and resumed normal activities. No major therapeutic trials in FM
      and CFS were reported over the past year.

PMID- 11224737
TI  - Epidemiology, etiology, diagnostic evaluation, and treatment of low back pain.
AB  - Low back pain affects a minority of individuals over 65 years of age. Four years
      after the onset of sciatica, the number of individuals working is independent of
      their workers' compensation status. A complex interaction of metalloproteinases,
      cytokines, chondrocytes, and macrophages are necessary for the resorption of
      herniated intervertebral discs. Positional magnetic resonance imaging in the
      seated extended posture identifies foraminal narrowing that is not visualized
      with conventional magnetic resonance studies. Compression associated with cauda
      equina syndrome must be reversed within 48 hours to preserve neurologic function.
      The gene for transforming growth factor can be transferred to intervertebral
      discs, resulting in increased proteogylcan production in a rabbit animal model.
      An aerobic exercise program is as effective as more expensive exercise programs
      in the treatment of chronic low back pain. Complementary therapies, willow bark
      and magnets, have marginal benefit for low back pain. Surgical intervention
      results in improved function for spinal stenosis patients.

PMID- 11224738
TI  - Rotator cuff disease.
AB  - The important role played by the rotator cuff in the stability and movement of
      the glenohumeral joint make it susceptible to damage and injury in patients of
      all age groups. A number of extrinsic and intrinsic mechanisms have been
      described for the development of rotator cuff disease, although it is more likely
      that the actual etiology in any one individual is multifactorial. The key to
      successful management in a particular patient is an accurate diagnosis of the
      underlying cause by thorough clinical examination and the use of appropriate
      investigations. The mainstay of treatment of patients with rotator cuff disease
      is nonoperative. Surgical intervention is usually considered only after failure
      of at least 6 months of conservative therapy. However, there are a few situations
      where early surgical intervention is indicated.

PMID- 11224739
TI  - Sports and other soft tissue injuries, tendinitis, bursitis, and occupation
      related syndromes.
AB  - Three topics are reviewed: iliopsoas bursitis (IPB), iliotibial band frictional
      syndrome (ITBFS), and Achilles tendinopathy. Although not frequently diagnosed,
      IPB may be more prevalent than what is commonly thought. Several excellent review
      articles are presented. Imaging studies are usually needed for confirmation of
      the diagnosis, and a report on magnetic resonance imaging is presented.
      Successful treatment of IPB with home exercise is reviewed. Because an increasing
      number of people are exercising, there is an increasing need to know the
      syndromes that can result from overuse, such as ITBFS. Several articles on the
      use of diagnostic ultrasonography and magnetic resonance imaging to aid in the
      confirmation of this entity are reviewed; one article explores the pathology of
      ITBFS in a cadaveric study. In the section of the treatment of ITBFS the authors
      review one article on exercise and one on surgery. Use of ultrasound to aid in
      the diagnosis of Achilles tendinopathy is reviewed, as well as risk factors
      related to developing it. Two articles on surgical treatment are reviewed.

PMID- 11224740
TI  - Achilles tendon injuries.
AB  - The Achilles tendon is the strongest tendon in the human body. Because most
      Achilles tendon injuries take place in sports and there has been an common
      upsurge in sporting activities, the number and incidence of the Achilles tendon
      overuse injuries and complete ruptures have increased in the industrialized
      countries during the last decades. The most common clinical diagnosis of Achilles
      overuse injuries is tendinopathy, which is characterized by a combination of pain
      and swelling in the Achilles tendon accompanied by impaired ability to perform
      strenuous activities. Most patients with Achilles tendon injury respond favorably
      to conservative treatment and only those who fail to respond to carefully
      followed nonoperative treatment should undergo surgery for repair. A complete
      rupture of the Achilles tendon usually occurs in sports that require jumping,
      running, and quick turns. Although histopathologic studies have shown that
      ruptured Achilles tendons include clear degenerative changes before the rupture,
      many of the Achilles tendon ruptures occur suddenly without any preceding signs
      or symptoms. Neither conservative nor operative treatment is a treatment of
      choice for the ruptured Achilles tendon. It is generally accepted that surgery
      should be performed on ruptured Achilles tendons in young, physically active
      patients and in those patients for whom the diagnosis or the treatment of the
      rupture has been delayed, whereas the results of conservative treatment are an
      acceptable outcome in older patients with sedentary lifestyles. Many important
      issues still remain unanswered concerning the cause, pathogenesis, diagnosis, and
      management of the Achilles tendon disorders. Only when these issues have been
      solved by well-controlled studies can tailored treatment protocols be created.

PMID- 11224741
TI  - Renal medicine and renal transplantation.

PMID- 11224742
TI  - Long-term allograft surveillance: the role of protocol biopsies.
AB  - The safety of the renal allograft biopsy and the standardization of allograft
      histopathology interpretation have renewed interest in the performance of
      protocol (surveillance) biopsies. Recent surveillance biopsy studies in the areas
      of pre-implantation and in the early and late post-transplant periods are
      discussed.

PMID- 11224743
TI  - Cardiovascular risk factors in kidney transplantation.
AB  - Classical and non-classical cardiovascular risk factors are common after renal
      transplantation, and they are effectively associated with the development of
      cardiovascular disease. Despite the absence of large, controlled clinical trials
      examining the effect of prevention strategies, therapies should not be withheld
      from renal transplant recipients with significant risk factors, because their
      risk of developing cardiovascular disease is at least as high as that of the
      general population.

PMID- 11224744
TI  - New immunosuppressive drugs: an update.
AB  - An increasing number of immunosuppressive drugs became available for clinical use
      over the past few decades. These include substances with recently recognized
      immunosuppressive properties, which needed careful evaluation in various trials
      before they could be approved for use in different diseases. The effectiveness of
      other agents was already established, but knowledge about their modes of action
      or the mechanisms that lead to side effects was acquired much later. This
      understanding also contributed to the development of new drugs that display
      synergistic effects or lack certain adverse effects. The greater choice afforded
      by such research endeavours allows us to select the best therapeutic strategy for
      an individual patient; however, this requires a comprehensive knowledge of the
      available options. The present review provides an update of current knowledge of
      the most important substances (including calcineurin and target of rapamycin
      inhibitors, regulators of gene expression, and inhibitors of purine and
      pyrimidine synthesis) and surveys some of the novel agents that are expected to
      play an important role in the future.

PMID- 11224745
TI  - New developments in the management of cytomegalovirus infection and disease after
      renal transplantation.
AB  - The clinical management of cytomegalovirus infection and disease in renal
      transplant recipients has recently been significantly improved with the
      availability of data on prophylaxis with oral ganciclovir and valacyclovir. In
      addition, significant progress in early diagnosis and the quantitation of viral
      load has been achieved. The influence of novel immunosuppressants on the clinical
      course of cytomegalovirus infection has been clarified to some extent by recent
      clinical data. The identification of risk factors for cytomegalovirus disease
      beyond seroconstellation and immunosuppression is an ongoing process that might
      lead to a more targeted use of antiviral agents, given the risk of ganciclovir
      resistance. The understanding of the effects of cytomegalovirus on long-term
      graft outcome still needs to be deepened in order to design cytomegalovirus
      specific interventions to improve graft survival.

PMID- 11224746
TI  - Renal transplantation in the elderly.
AB  - As the number of elderly patients suffering from end-stage renal disease has
      increased almost threefold during the past 20 years all over the world, new
      strategies for the treatment of such patients have been developed. Better
      screening has made renal transplantation a valuable resource in elderly end-stage
      renal disease patients. Improved immunosuppressive protocols as well as the
      expansion of the donor pool by using older and living donors for older recipients
      have improved patient survival rates as well as the quality of life in this
      patient population.

PMID- 11224747
TI  - Trends and perspectives in pancreas and simultaneous pancreas and kidney
      transplantation.
AB  - Pancreas transplantation is still the best option to achieve normoglycaemia and
      insulin independence in patients with type I diabetes. As a result of
      improvements in surgical techniques, immunosuppression and patient selection, one
      year survival rates of 95, 83, and 88% for patient, pancreas, and kidney
      survival, respectively, are reported for patients with simultaneous pancreas and
      kidney transplantation. The main goals for the future are to reduce postoperative
      morbidity, to identify the relevant indications for single pancreas
      transplantation, to adopt the best surgical technique for individual patients'
      needs (bladder versus enteric drainage with or without portal venous delivery of
      insulin), and to develop immunosuppressive strategies with low nephrotoxic and
      diabetogenic potential.

PMID- 11224748
TI  - Positron emission tomography in urological malignancy.
AB  - Positron emission tomography is a unique imaging modality with the capability of
      studying regional metabolism. The major clinical applications of positron
      emission tomography have been in the detection of brain, breast, cardiac, lung
      and colorectal tumours, as well as the evaluation of coronary artery disease by
      imaging the metabolism of heart muscle. In the field of urology, positron
      emission tomography has been evaluated in the relevant malignancies with
      promising results in certain areas and disappointing results in others. This
      article attempts to summarize recent advances in positron emission tomography
      scanning with regards to urological malignancy. At this stage positron emission
      tomography scanning is capable of visualizing urological tumours and associated
      lymph nodes and distal metastatic sites. However, its use is severely limited by
      the excretion of the most commonly used radioisotope via the urinary tract,
      making pelvic imaging particularly unrewarding. It is, however, undoubtedly
      capable of diagnosing malignancy in soft tissue masses or lymph nodes before
      these changes become apparent on conventional cross-sectional imaging modalities
      (computerized tomography or magnetic resonance imaging). Larger studies are
      required before it can be advocated for clinical use in the field of urology.

PMID- 11224749
TI  - Magnetic resonance imaging of the prostate.
AB  - Magnetic resonance imaging has been shown to be more accurate than other imaging
      modalities in the evaluation of both malignancies and various benign lesions of
      the prostate. Despite its superiority, because of its cost and low availability,
      magnetic resonance imaging should play a role as a problem-solver secondary to
      computed tomography or ultrasonography. The routine use of magnetic resonance
      imaging in the staging of prostate cancer before surgery cannot be justified on
      the basis of published data. Magnetic resonance imaging has been proved to be of
      value in the planning and delivery of different types of radiotherapy to patients
      with prostate cancer. Through the use of combined magnetic resonance imaging and
      the new modality, magnetic resonance spectroscopy, the accuracy and specificity
      of tumour detection and the delineation of tumour extent can be improved.
      Magnetic resonance technology is rapidly evolving, and in the near future, new
      possibilities such as biological imaging will have a great impact on magnetic
      resonance imaging of the prostate.

PMID- 11224750
TI  - Virtual endoscopy in urology.
AB  - Recent years have seen notable advances in virtual reality technology and
      increased interest in potential medical applications. Computed tomography and
      magnetic resonance imaging data sets, historically viewed as axial images, may
      now be used to construct a virtual reality endoscopic image, and navigator
      software systems allow the operator to 'fly' through the urinary tract.
      Technological evolution has improved the quality of reconstruction, as this is
      dependent on the software and data set, allowing virtual reality to begin to
      challenge endoscopic evaluation. This review describes the evolution of virtual
      reality in urology and the milestones of its current clinical use. Applications
      may become widespread in the diagnostic evaluation of common urological symptoms,
      the planning of surgery and the training of future urologists.

PMID- 11224751
TI  - Radiologic evaluations affecting surgical technique in ureteropelvic junction
      obstruction.
AB  - Ureteropelvic junction obstructions can be explored by radiographic methods
      including ultrasonography, intravenous pyelography, radionuclide scanning,
      magnetic resonance imaging and computerized tomography. The decision to operate
      on an ureteropelvic stricture is best given by the results of a radionuclide
      scan, which can demonstrate the obstruction. The operative technique is
      influenced by the presence of a polar artery, as this presence represents a
      danger when endopyelotomy is performed. The presence of a polar artery may be
      demonstrated by computerized tomography using helicoidal reconstruction. Magnetic
      resonance imaging with injection of gadolinium is also useful when available. The
      outcome and the results of the surgical procedure are also evaluated by
      radionuclide scanning.

PMID- 11224752
TI  - Angiographic evaluation and treatment of transplant renal artery stenosis.
AB  - Transplant renal artery stenosis is an uncommon but important complication of
      renal transplantation. It is a potentially reversible cause of patient morbidity
      and allograft dysfunction, which can present both early and late in the post
      transplant period. Although transplant renal artery stenosis can be detected
      using noninvasive imaging, definitive diagnosis and percutaneous treatment
      typically require the use of invasive angiographic techniques. In experienced
      hands, these studies can be performed safely, effectively and with a low risk of
      contrast induced nephrotoxicity when alternative contrast agents are used.

PMID- 11224753
TI  - A clinical comparison of the safety and efficacy of MultiHance (gadobenate
      dimeglumine) and Omniscan (Gadodiamide) in magnetic resonance imaging in patients
      with central nervous system pathology.
AB  - RATIONALE AND OBJECTIVES: The safety and diagnostic efficacy of MultiHance
      (gadobenate dimeglumine) in the central nervous system (CNS) were evaluated in a
      double-blind, multicenter, phase III clinical trial. METHODS: Two hundred five
      patients highly suspected of having a CNS lesion (by previous imaging exam) were
      enrolled at 16 sites in the United States. Patients were randomized to one of
      three incremental dosing regimens. Magnetic resonance imaging with Omniscan
      (gadodiamide) at doses of 0.1 and 0.3 mmol/kg was compared with MultiHance
      (gadobenate dimeglumine) at doses of 0.05 and 0.15 mmol/kg and at 0.1 and 0.2
      mmol/kg. RESULTS: Compared with predose images alone, efficacy was demonstrated
      in each of the gadobenate dimeglumine and gadodiamide groups (single and
      cumulative doses) as indicated by the level of diagnostic information, number of
      lesions detected, and contrast-to-noise ratio measurements. The level of
      diagnostic information from gadobenate dimeglumine at 0.1 mmol/kg was equivalent
      to that with gadodiamide at the same dose. One of the two blinded reviewers found
      equivalence between the gadobenate dimeglumine 0.05 mmol/kg dose and gadodiamide
      at 0.1 mmol/kg. Both reviewers found the level of diagnostic information to be
      equivalent after the second dose of contrast for all three dosing regimens. The
      cumulative doses of gadobenate dimeglumine were well tolerated and as safe as
      gadodiamide. CONCLUSIONS: Gadobenate dimeglumine is comparable to gadodiamide in
      terms of safety and efficacy for imaging of CNS lesions, with a possible
      advantage in imaging applications owing to enhanced T1 relaxivity.

PMID- 11224754
TI  - Detection of intracranial metastases: a multicenter, intrapatient comparison of
      gadobenate dimeglumine-enhanced MRI with routinely used contrast agents at equal
      dosage.
AB  - RATIONALE AND OBJECTIVES: To compare gadobenate dimeglumine (MultiHance) with
      other commercially available MRI contrast agents for the detection of
      intracranial metastases. METHODS: A retrospective assessment was performed on MR
      images from 22 patients enrolled in a prior phase II clinical trial of gadobenate
      dimeglumine. Each patient underwent two examinations: a first examination with
      one of three "comparator" agents (gadopentetate dimeglumine, gadodiamide, and
      gadoterate meglumine) at a dosage of either 0.1 or 0.2 mmol/kg, and then a
      similar examination with gadobenate dimeglumine at equal dosage. All images were
      evaluated randomly for lesion number and location in unpaired and then paired
      fashion by two independent, masked neuroradiologists. A third assessor performed
      quantitative assessments on the available complete sets of digitally recorded
      images (10 cases). RESULTS: The findings for the comparator agents were pooled.
      Sensitivity for lesion detection with gadobenate dimeglumine (93%-100%) was
      markedly superior to that of comparator-enhanced examinations (65%-73%). The
      increase of lesion-to-brain contrast of the main lesion was consistently greater
      with gadobenate dimeglumine than with comparator agents relative to unenhanced
      contrast (+43% vs. +27%). CONCLUSIONS: Gadobenate dimeglumine proved to be a more
      efficacious agent than comparator contrast agents for the detection of
      intracranial metastatic lesions: superior efficacy was noted by both reviewers
      for total lesion count as well as for sensitivity and positive predictive value
      for lesion detection. The higher relaxivity of gadobenate dimeglumine might
      explain the superior sensitivity of gadobenate dimeglumine-enhanced MRI for the
      detection of central nervous system metastases.

PMID- 11224755
TI  - Gd3+ complexes with slowly exchanging bound-water molecules may offer advantages
      in the design of responsive MR agents.
AB  - RATIONALE AND OBJECTIVES: Slow water exchange in Gd3+ complexes is generally
      considered detrimental to their use as MR contrast agents. The objective of this
      work was to demonstrate how this feature may serve as a useful template for the
      design of responsive MR agents. METHODS: Lanthanide (Ln) complexes of two
      1,4,7,10-tetraazacyclododecane-N,N',N",N'"-tetraacetic acid (DOTA)-tetraamide
      phosphonate (1) and phosphonate ester (2) ligands were studied by multinuclear
      (1H, 13C, 31P, and 17O) nuclear MR spectroscopy. RESULTS: The inner-sphere water
      lifetime in the Ln(2) complexes was much longer (tauM298 = 0.8-1.3 ms) than in
      the corresponding Ln(1) complexes. This allowed direct detection of the bound
      water molecule in europium(2) in water at 40 degrees C by 1H nuclear MR. The
      water relaxivity of gadolinium(2) was independent of pH between 8.5 and 6.0,
      whereas the relaxivity of gadolinium(1) increased more than twofold in this pH
      range. CONCLUSIONS: T1-weighted images of phantoms containing gadolinium(1) at
      different pH values demonstrate the efficacy of this complex as a pH-sensitive MR
      contrast agent.

PMID- 11224756
TI  - Iomeprol: current and future profile of a radiocontrast agent.
AB  - RATIONALE AND OBJECTIVES: To review the safety and efficacy profiles of iomeprol
      by examining the most indicative comparative clinical studies of iomeprol with
      widely used low-osmolar ionic or nonionic contrast agents, and to illustrate the
      recent development in iomeprol liposomal formulations for liver imaging and
      intravascular enhancement. METHODS: Randomized, double-blind, comparative studies
      were performed of iomeprol versus iopamidol, iopromide, ioxaglate, iopentol,
      iodixanol, ioversol, and iohexol. In all studies, safety controls included pre-
      and postadministration physical examinations, monitoring of vital signs,
      electrocardiography, clinical laboratory investigations, and 24- or 72-hour
      postadministration monitoring of patients for adverse events. Technically
      adequate images were rated for diagnostic efficacy by masked assessors. RESULTS:
      Iomeprol showed similar safety and diagnostic efficacy compared with the nonionic
      monomers iopamidol, iohexol, and ioversol, and no statistically significant
      differences were observed. No differences in diagnostic efficacy between iomeprol
      and iopromide were observed, but in one study on 1,200 patients, the incidence of
      adverse events and adverse reactions was significantly higher with iopromide than
      with iomeprol. Iomeprol caused significantly less heat/pain than iopentol in one
      study; it showed similar safety and tolerability to the nonionic dimer iodixanol,
      the two agents causing no or modest, superimposable pain and heat sensation at
      injection and showing similar renal tolerability after intra-arterial injection.
      A comparison of iomeprol versus ionic dimer ioxaglate in 2,000 patients
      undergoing percutaneous coronary interventions showed that the incidence of
      thrombus-related events was similar with the two agents, but ioxaglate caused a
      significantly higher incidence of allergy-like reactions. First results with
      iomeprol-containing liposomal formulations show that these agents may facilitate
      the CT assessment of intrahepatic malignancies and CT angiography procedures.
      CONCLUSIONS: The overall results of numerous randomized, double-blind,
      comparative clinical studies in a variety of indications show that the diagnostic
      efficacy of iomeprol solutions does not differ significantly from that of the low
      osmolar contrast media available on the marketplace when similar iodine strengths
      are used, although iomeprol may have better tolerability and safety than the
      ionic dimer and some of the nonionic monomers in selective applications. First
      results obtained with iomeprol-containing liposomal formulations are promising
      and may foster additional clinical testing.

PMID- 11224757
TI  - MRI contrast enhancement of necrosis by MP-2269 and gadophrin-2 in a rat model of
      liver infarction.
AB  - RATIONALE AND OBJECTIVES: The mechanisms of action leading to specific
      localization of necrosis-avid contrast agents (NACAs) such as gadophrin-2 are not
      well defined. It has been suggested recently that agents with a high degree of
      serum albumin binding may also serve as NACAs by virtue of nonspecific
      hydrophobic interactions. The present MRI-histomorphology correlation study was
      conducted to verify the likelihood of the proposed albumin-binding mechanism by
      comparing an albumin-binding blood pool agent, MP-2269, with gadophrin-2 in a rat
      model of reperfused liver infarction. METHODS: Reperfused infarction in the right
      liver lobe was surgically induced in six rats. Serial T1-weighted MRI was
      performed before and after intravenous injection of MP-2269 at 0.05 mmol/kg and
      repeated in the same rats 24 hours later after intravenous injection of gadophrin
      2 at the same dosage (0.05 mmol/kg). The MR images were matched with
      corresponding histomorphological findings. The signal intensity and contrast
      ratio of infarcted and normal hepatic lobes were quantified and compared between
      the two agents during the postcontrast course. RESULTS: Before contrast, the
      infarcted lobe was indiscernible from normal liver on T1-weighted MRI. Shortly
      after injection of both MP-2269 and gadophrin-2, a negative contrast occurred
      between infarcted and normal liver because of a strong liver signal intensity
      enhancement and an inferior uptake in the necrotic liver. On delayed phase (>60
      minutes), a necrosis-specific contrast enhancement (contrast ratio 1.6) developed
      with gadophrin-2 but not with MP-2269. The MR images matched well with
      corresponding histomorphological findings. CONCLUSIONS: Although both MP-2269 and
      gadophrin-2 feature an albumin-binding capacity, only gadophrin-2 displayed a
      persistent necrosis-specific contrast enhancement in the rat model of reperfused
      liver infarction. Therefore, the role of albumin binding in the mechanisms of
      NACAs should be reevaluated.

PMID- 11224758
TI  - Clinical safety of SonoVue, a new contrast agent for ultrasound imaging, in
      healthy volunteers and in patients with chronic obstructive pulmonary disease.
AB  - RATIONALE AND OBJECTIVES: To evaluate the safety profile of SonoVue, a new echo
      contrast agent based on stabilized sulfur hexafluoride (SF6) microbubbles, in
      healthy volunteers and in patients with chronic obstructive pulmonary disease
      (COPD). METHODS: Safety and tolerability of SonoVue were evaluated in 66 healthy
      volunteers during two placebo-controlled phase I studies (a single intravenous
      ascending-dose study in 36 volunteers given SonoVue doses of 0.003 to 0.12 mL/kg
      and a multiple-dose study in 30 subjects given cumulative doses of 0.15 to 0.6
      mL/kg) and in 12 patients with COPD of various degrees of clinical severity, who
      were given SonoVue at a dosage of 4 mL (corresponding to 0.057 mL/kg in a 70-kg
      patient). Adverse events were monitored up to 48 to 72 hours after
      administration. All volunteers underwent extensive safety assessments (monitoring
      of vital signs, electrocardiogram, blood oxygen saturation, laboratory
      assessments, and Mini-Mental test) up to 24 to 72 hours after administration. In
      addition, patients with COPD underwent specific lung function tests, such as
      forced expiratory volume, forced vital capacity, and forced midexpiratory flow.
      RESULTS: No serious adverse events occurred throughout the study. All nonserious
      adverse events were minor, mild, and rapidly self-resolving. No difference in the
      incidence of adverse events was observed among the various dosages of SonoVue and
      between SonoVue and placebo. There were no clinically significant changes in any
      of the safety assessments. No statistically significant differences between
      SonoVue and placebo were observed in mean forced expiratory volume, forced vital
      capacity, or forced midexpiratory flow levels. No substantial changes from
      baseline in blood oxygen saturation were observed for either study agent at any
      postinjection time point. CONCLUSIONS: SonoVue showed a good safety profile both
      in healthy subjects and in patients with COPD.

PMID- 11224760
TI  - Stability of MRI paramagnetic contrast media: a proton relaxometric protocol for
      transmetallation assessment.
AB  - RATIONALE AND OBJECTIVES: The suitability of paramagnetic complexes as magnetic
      resonance contrast agents depends on various factors such as their relaxivity,
      stability, selectivity, and the inertness toward transmetallation by endogenous
      ions. The transmetallation of a series of 18 gadolinium complexes by the Zn2+ ion
      was studied in vitro by proton relaxometry. METHODS: Transmetallation was
      analyzed through the evolution of the paramagnetic longitudinal relaxation rate
      of water protons at 37 degrees C in pH = 7 phosphate buffer solutions containing
      2.5 mmol/L of the gadolinium complexes and 2.5 mmol/L zinc chloride. The
      measurements were performed at 0.47 T over a period of at least 3 days. RESULTS:
      The results confirm the high stability of macrocyclic systems and a high
      sensitivity of Gd-diethylenetriamine-pentaacetic acid (DTPA) derivatives to
      transmetallation by Zn2+ ions. The decreasing order of stability with respect to
      metal exchange is as follows: Gd-macrocyclics > Gd-C-functionalized DTPA > Gd
      DTPA > primary and secondary Gd-DTPA bisamides. The ternary bisamide analyzed in
      this study [Gd-DTPA-1,11-bisbismethylamino-1,11-dioxo-3,6,9-triaza-3,6,9
      tris(carboxymethyl)undecane] is more stable than the parent compound Gd-DTPA.
      CONCLUSIONS: A simple relaxometric protocol has been successfully developed to
      study the in vitro transmetallation process of gadolinium complexes. The
      importance of the functionalization and substitution of the DTPA-like complexes
      is clearly shown.

PMID- 11224759
TI  - Volumetry of ventilated airspaces by 3He MRI: preliminary results.
AB  - RATIONALE AND OBJECTIVES: To develop a validated post-processing routine for
      volumetry of the ventilated airspaces by 3He MRI. METHODS: 3Helium MRI and
      pulmonary function tests were performed in seven healthy volunteers. After
      segmentation of ventilated airspaces, their volumes were calculated. Functional
      residual capacity (FRC) was used as a reference. For comparison of absolute
      volumes, correction factors were evaluated. RESULTS: Mean lung volume (+/-
      standard deviation) calculated from 3He MRI was 4,082 +/- 908 mL and mean FRC was
      3,696 +/- 1166 mL, with a mean difference of 386 mL (r = 0.88). After correction
      for the relative pulmonary air content (factor 0.82), posture (0.72), and the
      individual tidal volume, 3He MRI volume was 3,348 +/- 744 mL and mean FRC was
      3,422 +/- 817 mL, with the mean difference down to -74 mL (r = 0.9). Comparison
      on an individual basis confirmed an improvement in the estimation of absolute
      lung volume. CONCLUSIONS: Volumetry of ventilated lung from 3He MRI shows high
      correlation and good agreement with the results of pulmonary function tests.

PMID- 11224761
TI  - A review of contrast media research in 1999-2000.
AB  - Contrast media research published during the years 1999 and 2000 is reviewed in
      this article, in terms of relevance to developments within the field of
      diagnostic radiology. The primary focus is on publications from the journal
      Investigative Radiology, which publishes much of the clinical and laboratory
      research performed in this field. The journals Radiology and the American Journal
      of Roentgenology are dominant in the field of diagnostic radiology and together
      publish more than 10 times the number of articles as appear each year in
      Investigative Radiology. However, in 1999 for example, these two journals
      together published fewer articles than did Investigative Radiology alone that
      concerned basic (animal) research with contrast media. Thirty-six percent of the
      articles in Investigative Radiology in 1999 had a primary focus on contrast media
      and 18% on basic (animal) research with contrast media. To make this review more
      complete, articles from other major journals are cited and discussed, as needed,
      to provide supplemental information in the few areas not well covered by articles
      in Investigative Radiology. The safety of contrast media is always an important
      topic and research continues to be performed in this area, both to explore
      fundamental issues regarding iodinated contrast media and also to establish the
      overall safety profile of new magnetic resonance (MR) and ultrasound agents. In
      regard to preclinical investigations, most of the work performed in the last 2
      years has been with MR and ultrasound. In MR, research efforts continue to be
      focused on the development of targeted agents. In ultrasound, research efforts
      are split between studies looking at new imaging methods and early studies of
      targeted agents. In regard to the clinical application of contrast media, the
      published literature continues to be dominated by MR. Investigations include the
      study of disease in clinical trials and in animal models. A large number of
      studies continue to be published in regard to new techniques and applications
      within the field of contrast-enhanced magnetic resonance angiography. This field
      represents the single, largest new clinical application of contrast media in MR
      to emerge in the last decade. New clinical research continues to be published
      regarding the use of contrast media in computed tomography (CT), ultrasound, and
      x-ray angiography. The introduction of spiral CT (together with the multidetector
      scanners) has led to greater utilization of this modality, as well as intravenous
      iodinated contrast media. The number of publications regarding clinical
      applications of intravenously injected ultrasound contrast agents remains low,
      with the high expectations in regard to growth (in terms of number of exams using
      contrast) of the last decade yet to be fulfilled.

PMID- 11224763
TI  - Early oral feeding following total laryngectomy.
AB  - OBJECTIVES: The time to begin oral feeding after total laryngectomy remains a
      subject of debate among head and neck surgeons. The prevailing assumption is that
      early initiation of oral feeding may cause pharyngocutaneous fistula; thus, the
      common practice of initiating oral feeding after a period of 7 to 10 days. The
      objective of the study was to demonstrate the feasibility and safety of oral
      feeding 48 hours after total laryngectomy. STUDY DESIGN: Two-part study includes,
      first, a sequential study and, second, a prospective analysis of our practice.
      METHODS: Patients undergoing total laryngectomy without partial pharyngectomy or
      radiation treatment (except irradiation through small ports for a T1 or T2
      glottic carcinoma) were included. In the first, sequential part of the study
      (part I), a group of 18 patients who were fed 7 to 10 days after total
      laryngectomy (control group) was compared with a group of 20 patients who
      received oral feeding within 48 hours. To confirm the results of part I, a
      prospective analysis of this practice was conducted (part II) in which 35
      additional patients who met the above criteria were fed within 48 hours after
      surgery. RESULTS: In part I, pharyngocutaneous fistula occurred in one patient
      (5%) in the early feeding group and in two patients (11%) in the control group.
      In part II, pharyngocutaneous fistula occurred in one patient (2.8%). Overall,
      fistula occurred in two patients in the combined early feeding group (3.6%). This
      rate of pharyngocutaneous fistula compares favorably with the fistula rate in the
      control group of 18 patients. Pharyngeal stricture that required dilation
      occurred in three of our patients in the study group and two in the control group
      (5.5% vs. 11%, respectively). The length of hospital stay was significantly
      shortened from 12 to 7 days. CONCLUSION: Our results indicate that in this
      patient population initiation of oral feeding 48 hours after total laryngectomy
      is a safe clinical practice.

PMID- 11224764
TI  - Technetium 99m single positron emission computed tomography scanning for
      assessing mandible invasion in oral cavity cancer.
AB  - OBJECTIVES: To study the accuracy of single positron emission computed tomography
      (SPECT) scanning and compare its results to clinical examination, Panorex, and
      computed tomography (CT) scanning with respect to determining mandibular invasion
      by oral cavity and oropharyngeal cancer, and to define the role of SPECT scanning
      in the preoperative assessment of oromandibular cancer. STUDY DESIGN: Prospective
      study of 38 patients who underwent technetium 99m SPECT scanning as part of their
      preoperative clinical assessment for cancer at risk of invading the mandible. All
      patients underwent partial or segmental mandibulectomy as part of their surgical
      management. METHODS: A data protocol was used to tabulate patient demographics,
      tumor characteristics and results of preoperative tests as patients were enrolled
      into the study. Following surgical treatment, these data were correlated with
      histopathological findings. Detailed analysis was performed to assess the
      tabulated data. RESULTS: The SPECT scanning demonstrated an 87% overall accuracy
      in predicting bone invasion compared with 71% for clinical examination, CT
      scanning, and Panorex x-rays. The SPECT scanning was significantly more sensitive
      (95%) than either CT scans (55%) or Panorex x-rays (50%). Notably SPECT scanning
      demonstrated a considerable improvement in specificity (72%) compared with
      conventional radionuclide scanning. Although not as specific as CT scanning or
      plain films, SPECT scanning was significantly more effective in ruling out
      disease than was clinical examination. CONCLUSIONS: Preoperative SPECT scanning
      used in combination with clinical examination, CT scanning, and Panorex x-rays to
      assess patients at risk for mandible involvement by oral cavity cancer can
      improve the accuracy of predicting bone invasion and help in appropriate
      treatment planning so as to safely reduce the proportion of disease-free jaws
      resected.

PMID- 11224765
TI  - The anatomical basis of the Abbe flap.
AB  - OBJECTIVES: Objective of the study were 1) to determine the course, including
      specific relationship to the vermilion border, free margin of the lip, and
      orbicularis oris and number of the superior and inferior labial arteries, and 2)
      to discuss the relevance of this anatomy to design of the Abbe flap. STUDY
      DESIGN: Detailed anatomical dissections of the mid and lower face of injected
      cadaver heads. METHODS: Sixteen superior labial arteries and 15 inferior labial
      arteries in 9 adult cadaver heads ranging in age from 41 to 90 years were
      studied. RESULTS: The superior labial artery was a single vessel in all cases. At
      the oral commissure the vessel was superior to the vermilion border in 94% of the
      dissections. At the midline the vessel was within the vermilion border in 75% of
      dissections. The vessel was found within the orbicularis oris in 19% of
      dissections and between the mucosa and the orbicularis oris in 81% of
      dissections. The inferior labial artery was a single vessel in all dissections.
      Its course was variable in position relative to the vermilion border and to its
      take-off from the facial artery. In the central portion of the lip the vessel was
      found within the orbicularis oris in 13% of dissections and between the mucosa
      and the orbicularis oris in 87% of dissections. CONCLUSIONS: The superior labial
      artery is found within 10 mm of the free margin of the upper lip. The inferior
      labial artery is variable in its course, varying up to 15 mm from the free margin
      of the lower lip.

PMID- 11224767
TI  - Detection of fungi in the nasal mucosa using polymerase chain reaction.
AB  - HYPOTHESIS: Fungi have been increasingly recognized as important pathogens in
      sinusitis. However, detection of fungus with conventional culture techniques is
      insensitive and unreliable. Polymerase chain reaction (PCR) is an exquisitely
      sensitive assay that can detect the DNA of 10 or less fungal elements. The aim of
      this study was to compare the sensitivity of conventional culture techniques
      using PCR analysis. METHODS: Nasal swabs and DNA samples were collected from the
      nasal cavities of control subjects and patients with chronic sinusitis. Fungal
      specific PCR analysis and standard cultures were performed on every sample. chi2
      analysis was used to test for statistical differences between groups. RESULTS:
      PCR analysis detected fungal DNA in 42% and 40% of control subjects and patients
      with chronic sinusitis while standard cultures were positive in 7% and 0%,
      respectively. There was no statistically significant difference in the prevalence
      of fungi in the normal volunteers and patients with chronic rhinosinusitis.
      CONCLUSION: PCR is significantly more sensitive than nasal swab cultures in
      detecting the presence of fungi in nasal mucosa. In addition, our study suggests
      that the presence of fungi alone is insufficient to implicate it as the pathogen
      in chronic sinusitis.

PMID- 11224766
TI  - Validation of a patient-graded instrument for facial nerve paralysis: the FaCE
      scale.
AB  - OBJECTIVE: To develop and validate a patient-based instrument to measure both
      facial impairment and disability, the Facial Clinimetric Evaluation (FaCE) Scale.
      STUDY DESIGN: Prospective instrument validation. METHODS: Eighty-six patients
      with a documented history of facial paralysis completed a preliminary, 51-item
      instrument (alpha FaCE Scale), as well as the previously developed Facial
      Disability Index (FDI) and the Medical Outcomes Study Short Form 36 Item
      Questionnaire (SF-36). Two weeks after completing these instruments, 76 patients
      again completed the alpha FaCE Scale. Forty-one of the patients were also
      evaluated using the House-Brackmann Grading System (HBGS) and the Facial Grading
      System (FGS). RESULTS: Exploratory principal component factor analysis grouped 15
      FaCE Scale items into 6 impairment and disability categories (domains), forming
      the beta FaCE Scale. Overall, the test-retest reliability of the FaCE Scale was
      high (Spearman's correlation coefficient (r) = 0.88, P <.01), as were the
      reliability coefficients of the individual domains (r = 0.81-0.92, P <.01). The
      FaCE Scale domains showed appropriate correlation to global visual analogue scale
      questions posed on the original alpha FaCE Scale (r = 0.65-0.81, P <.01).
      Overall, the FaCE Scale showed significant correlation with HBGS and FGS scores
      (r = -0.55 and 0.57, respectively; P <.01). However, not all FaCE Scale domains
      correlated with the HBGS and FGS scores. CONCLUSIONS: A reliable and valid
      patient-based system to measure impairment and disability in facial paralysis has
      been developed. This system appears to be better than traditional, physician
      graded scales for evaluating quality-of-life issues affected by facial
      disability.

PMID- 11224768
TI  - The predictive value of serum interleukins in recurrent respiratory
      papillomatosis: a preliminary study.
AB  - OBJECTIVE: IL-2 is the primary interleukin responsible for activation of the cell
      mediated (Th1) arm of the immune response. Our objective was to determine whether
      a correlation existed between circulating levels of interleukin-2 as well as its
      soluble receptor (sIL-2R) and the clinical course of recurrent respiratory
      papillomatosis. METHODS AND MATERIALS: Fifteen children with a histological
      diagnosis of RRP were recruited. Age at the time of study, time since first
      diagnosis, and number of surgical interventions were recorded. The number of
      surgically treated recurrences per year was then calculated. We obtained serum
      samples from each of these 15 children and from 10 normal control subjects. We
      then performed in vitro determination of serum IL-2 and soluble IL-2 receptor
      levels using enzyme-linked immunosorbent assay (ELISA) techniques. RESULTS: IL-2
      was significantly lower (136.6 vs. 199.9 pg/mL, P =.035) in papilloma patients
      than in control subjects. IL-2R was also lower in papilloma patients (531.7 vs.
      785.8 U/mL, P =.025). There was no statistical age difference between the
      papilloma and control groups. Among patients with papillomatosis, IL-2 and sIL-2R
      levels were significantly higher in those with aggressive disease (>4 surgically
      treated recurrences per year) versus non-aggressive disease (179.2 vs. 99.2
      pg/mL, P =.024; and 697 vs. 387 U/mL, P =.022). Age was also significantly lower
      in the aggressive papilloma group (P =.002). CONCLUSIONS: Levels of interleukin-2
      and IL-2 receptor were significantly lower in patients with recurrent respiratory
      papillomatosis compared with normal children. These data support the presence of
      an aberrant cell-mediated immune response in children with recurrent respiratory
      papillomatosis.

PMID- 11224770
TI  - Computed tomographic and anatomical analysis of the basal lamellas in the ethmoid
      sinus.
AB  - OBJECTIVES: To investigate the exact anatomical structure of the lamellas in the
      ethmoid sinus by computed tomography (CT) and anatomical analysis. STUDY DESIGN:
      Cadaver dissections and CT scans were used to compare lamellar structures and
      their radiological images. METHODS: Anatomical microdissection of 100 midsagittal
      sections from adult cadaver head specimens were examined and compared with those
      of sagittal CT scans at 1-mm intervals. RESULTS: The posteroinferior end of the
      uncinate process attaching to the inferior turbinate divided the fontanelle into
      the anterior and posterior portions in the majority of cases. The basal lamellas
      of the bulla ethmoidalis were subdivided into three major types. The
      posteroinferior portion of its basal lamella was connected to the lower
      horizontal portion of the third basal lamella in all cases. The anterior
      indentation of the third lamella was identified in nine cases, but there was no
      indentation in the posterior direction. The basal lamella of the superior
      turbinate was attached to the skull base superiorly either separately or fused to
      the third lamella, and its posteroinferior portion was attached to the lowest
      portion of the anterior wall of the sphenoid sinus. The supreme turbinate existed
      in 50 cases; however, its basal lamella was identified in only 15 cases.
      CONCLUSIONS: Our results indicate that the lamellas of the ethmoid sinus have
      relatively uniform patterns, although there is variability in shape. It is hoped
      that this study will provide surgeons with a more detailed structure of the basal
      lamellas for better surgical results and lower complication rates.

PMID- 11224769
TI  - Olfaction and its alteration by nasal obstruction, rhinitis, and rhinosinusitis.
AB  - The sense of smell has been largely ignored by otorhinolaryngologists, even
      though 1) its medical stewardship falls within their specialty's purview, 2)
      olfactory dysfunction is not uncommon in the general population, and 3) disorders
      of olfaction have significant quality of life, nutritional, and safety
      consequences. This report provides a succinct overview of the major intranasal
      neural systems present in humans (namely, cranial nerves O, I, and V, and the
      nonfunctional accessory [vomeronasal] organ system), along with a summary of
      notable findings resulting from the application of modern olfactory tests to
      patient populations, emphasizing diseases of the nose. Such tests have led to the
      discovery of significant influences of age, gender, smoking, toxic exposure, and
      genetics on the ability to smell. Within the field of otorhinolaryngology, they
      have revealed that 1) surgical and medical interventions in patients with
      rhinosinusitis do not, on average, lead to complete recovery of olfactory
      function, despite common beliefs to the contrary, and 2) associations are
      generally lacking between measures of airway patency and olfactory function in
      such cases. These findings have thrown into question the dogma that olfactory
      loss in rhinosinusitis is attributable primarily to blockage of airflow to the
      receptors and have led to histopathological studies demonstrating significant
      olfactory epithelial compromise in sinonasal syndromes.

PMID- 11224772
TI  - External osteotomy in rhinoplasty.
AB  - OBJECTIVES: To compare external and internal lateral osteotomy in rhinoplasty.
      STUDY DESIGN: Retrospective review and study on cadavers. METHODS: One hundred
      forty-two patients who underwent aesthetic rhinoplasty were examined. The
      following criteria were taken into consideration: edema and ecchymosis around the
      eyes, the degree of closure of the roof, symmetry and level of fractures,
      solidity of the bone pyramid, and any scarring at the access point of the
      osteotome. In the last 25 patients who had surgery, a nasal endoscopy with
      optical fibers was carried out to evaluate any damage to the mucosa caused by the
      2-mm osteotome. Furthermore, to compare the two routes in vivo, for five of these
      patients a lateral osteotomy was carried out externally for one side and
      internally for the other. Lateral osteotomy were performed on five cadavers by an
      external route on one side and by an internal one on the other. A midface
      degloving procedure was performed to expose the osteotomy sites. RESULTS: Edema
      and ecchymosis were always much less severe in patients who were treated with
      external osteotomy. The control of the fracture line was always excellent.
      Endoscopic evaluation and study on cadavers revealed damages to the mucosa caused
      from the internal osteotomy and a better control of fracture line in external
      osteotomy. CONCLUSIONS: External osteotomy is an easy and precise approach.
      Because the fracture is of a greenstick type, the bone stumps are stable. The
      reduced bleeding reduces the formation of edemas and ecchymosis around the eyes.
      The damage to the nasal mucosa is minimal, and the cutaneous scars are virtually
      invisible a month after surgery.

PMID- 11224771
TI  - Giant ethmoid osteoma with orbital extension, a nasoendoscopic approach using an
      intranasal drill.
AB  - OBJECTIVE: Ethmoid osteoma is a slow-growing, benign, and encapsulated bony
      tumor. Symptoms occur earlier than with osteomas of the frontal sinus because of
      the small volume of the ethmoid sinus. Interestingly, orbital extension is
      uncommon. Treatment remains controversial, with open procedures typically being
      used. In this article, we present a less invasive yet safe and effective approach
      to treatment. STUDY DESIGN: A nasoendoscopic approach using a Stammberger-Saches
      intranasal drill was developed for treatment of patients with ethmoid osteoma,
      with or without orbital extension. Between 1995 to 1999, seven patients underwent
      the new surgical procedure. METHODS: All procedures were performed under general
      anesthesia. Using 0 degrees and 30 degrees endoscopes, surface anesthesia of the
      nasal mucosa was performed, the anterior ethmoid cell was resected, and the
      whitish osteoma found. The osteoma was drilled out inferolaterally to
      superomedially. In the patient with orbital extension, a double-ended blunt
      elevator was used to separate the remaining osteoma from the lamina papyracea and
      to push the residual osteoma medially toward the nasal septum. With alternate
      drilling and elevation, the osteoma was gently removed. The surgical site was
      then packed. RESULTS: The method successfully treated all patients. There were no
      major complications. The single patient with orbital extension had mild
      postoperative periorbital ecchymoses. Nasoendoscopy showed normal
      epithelialization 4 to 6 weeks after surgery. Computed tomography showed no
      residual tumors 6 months after surgery. CONCLUSION: The 30 degrees nasoendoscopic
      approach using an intranasal drill provides a good operative field and is a safe
      and effective technique, with the potential to become the treatment of choice in
      selected cases.

PMID- 11224773
TI  - Pretreatment with portal venous ultraviolet B-irradiated donor alloantigen
      promotes donor-specific tolerance to rat nerve allografts.
AB  - OBJECTIVE: To determine if a single intraportal inoculation of ultraviolet B
      irradiated (UVB) donor splenocytes can prevent nerve allograft rejection and
      confer donor-specific immunotolerance to rat nerve allograft segments. METHODS:
      Age-matched, class I and class II major histocompatibility complex (MHC)
      mismatched Buffalo (RT1b) rats were transplanted with a syngeneic nerve isograft,
      a Lewis (RT1l) nerve allograft, or a Brown-Norway (RT1n) rat nerve allograft
      segment. Control Buffalo rats in group I received a 3.0-cm Lewis (RT11) sciatic
      posterior tibial interposition nerve allograft without pretreatment; group II
      Buffalo rats received a syngeneic Buffalo nerve isograft without pretreatment.
      Group III Buffalo recipients were inoculated with 2.5 x 107 UVB-irradiated Lewis
      donor splenocyte cells by portal venous administration 7 days before
      transplantation with a 3.0-cm sciatic-posterior tibial nerve allograft from a
      Lewis (RT11) or a third party Brown-Norway rat (RT1n) donor (group IV). Nerve
      graft regeneration was assessed with walking track analysis, nerve conduction
      studies, retrograde neural tracing, nerve graft histology, and morphometry.
      Recipient immune tolerance was assessed through in vitro immunological
      assessment. RESULTS: Pretreatment with UVB-irradiated donor splenocytes 7 days
      before transplantation prevented nerve allograft rejection. Pretreated animals
      receiving a nerve allograft recovered limb function, and demonstrated
      morphological, histological, and electrophysiologic parameters of nerve
      regeneration similar to that measured in rats receiving a nerve isograft. In
      vitro immunological assessment by mixed lymphocyte culture (MLC), cytotoxic T
      lymphocyte (CTL) assay, limiting dilution analysis (LDA) of helper (pTH) and
      cytotoxic (pCTL) precursor frequencies, and IL-2 production demonstrated a marked
      donor-specific suppression in allografted animals pretreated with intraportal UVB
      irradiated donor splenocytes. These assessments correlated with indefinite
      acceptance of donor nerve allografts. CONCLUSIONS: A single pretreatment with a
      single intraportal dose of UVB-modified donor antigen specifically induces
      tolerance to peripheral nerve allografts in rats.

PMID- 11224774
TI  - Frequency and localization of the putative vomeronasal organ in humans in
      relation to age and gender.
AB  - OBJECTIVES/HYPOTHESES: In many species the vomeronasal organ (VNO) serves as a
      chemosensory organ in addition to the olfactory system. The present investigation
      was undertaken to study 1) the frequency of monolateral or bilateral detection of
      the putative VNO (pVNO) in humans, 2) its localization in humans, and 3) whether
      detectability of the pVNO varies with age or gender. STUDY DESIGN: Prospective.
      METHODS: A total of 173 subjects participated in this study (88 women and 85 men;
      age range, 2-91 y). Inspection of the nose was performed with a speculum and a 30
      degrees endoscope. The exact localization of the VNO was measured with custom
      built rulers. RESULTS: The study revealed the following major results: 1) A pVNO
      is detectable in approximately two-thirds of the population and bilateral pVNOs
      are present in approximately 40% of investigated subjects, 2) its localization on
      the left and right nasal septum is almost symmetrical, and 3) and detectability
      of the pVNO is not related to age or gender. CONCLUSIONS: The present data
      indicated that the pVNO is present in approximately two-thirds of the population.
      This value may be biased by methodological or biological factors; nevertheless,
      it indicates that the pVNO is not observed in all humans regardless of age and
      gender. Thus, considering its variability in shape and immunohistochemical
      characteristics and the missing nerval connections between the peripheral "organ"
      and the central nervous system, the present results are not suited to argue for a
      functional significance of the pVNO in humans.

PMID- 11224775
TI  - Autologous transplantation of fascia into the vocal fold: long-term results of a
      new phonosurgical technique for glottal incompetence.
AB  - OBJECTIVES: To study the long-term results of autologous transplantation of
      fascia into the vocal fold, and to evaluate our use of autologous transplantation
      instead of bovine collagen injection in cases of glottal incompetence. STUDY
      DESIGN: Retrospective study of the patients who have undergone autologous fascia
      transplantation using our new technique. METHODS: Follow-up studies were
      performed for at least 1 year (up to 3 y) on 9 autologous fascia transplant
      patients (6 cases with type 1 procedures and 3 cases with type 2 procedures).
      Clinical observations, including laryngeal stroboscopy, and measurement of
      maximum phonation time (MPT) were carried out. RESULTS: During 3 months after
      autologous fascia transplantation, MPT gradually increased and stroboscopy showed
      improved glottal closure. These improvements continued beyond 1 year in all cases
      of type 1 surgery and 2 of 3 cases of type 2 surgery. CONCLUSIONS: Autologous
      transplantation of fascia into the vocal folds as a phonosurgical treatment for
      glottal incompetence yields excellent long-term results. Temporal fascia appears
      to be a highly suitable tissue for transplantation in Reinke's space. However,
      the fascia is less suitable for transplantation in the muscle. We speculate that
      transplantation of temporal fascia leads to regeneration of vocal fold tissue,
      perhaps using a mechanism similar to stem cell transplantation in other organs.

PMID- 11224776
TI  - The clinical features of functional dysphonia.
AB  - OBJECTIVE: This report aims to study the prevalence of features of laryngeal
      muscle tension in a population of patients with functional dysphonia (FD) and
      nondysphonic control subjects. STUDY DESIGN: Prospective control-blinded, cross
      sectional study. METHODS: We reported on a prospective control-blinded, cross
      sectional study of the prevalence of the six features described by Van Lawrence
      and the six features incorporated in the Morrison-Rammage classification. A
      senior laryngologist and senior speech pathologist independently rated sound
      free, random-sequence video laryngoscopies of 51 patients with FD and 52
      nondysphonic control subjects. Assessments were made of the presence or absence
      of the 12 laryngoscopic features of laryngeal dysfunction, and an overall rating
      made of the vocal technique as "normal" or "abnormal." RESULTS: More than 60% of
      the control population demonstrated 1 or more of the 12 features of
      hyperfunction. There was no significant difference in the prevalence of the six
      Van Lawrence features, the six Morrison-Rammage features, or the total number of
      abnormal features between patients with FD and control subjects. On overall
      assessment, both assessors noted a high prevalence (50% and 36%, respectively) of
      abnormal vocal technique in the control population. There was no statistical
      difference in the total number of abnormal features observed between patients
      with FD and control subjects. Positive predictive value calculations showed that
      the presence of a clinical feature, at best, presented a 75% chance of correctly
      identifying a patient with FD and, at worst, a 50% chance. CONCLUSION: The
      laryngoscopy features commonly associated with FD are frequently prevalent in the
      nondysphonic population and fail to distinguish patients with FD from normal
      subjects.

PMID- 11224777
TI  - Sleep-disordered breathing: radiofrequency thermal ablation is a promising new
      treatment possibility.
AB  - OBJECTIVES: The aim of this study was to assess the efficacy and morbidity of
      radiofrequency thermal ablation of the soft palate in subjects with sleep
      disordered breathing. STUDY DESIGN: Prospective, nonrandomized study. Outpatient
      treatment and an extended follow-up time of 12 months. METHODS: Twenty-one
      healthy men who were 18 to 60 years of age (median age, 44 y) with sleep
      disordered breathing were enrolled to the study. All the patients had habitual
      snoring for at least 1 year that was associated with excessive daytime sleepiness
      interfering with social or professional activities. Radiofrequency energy was
      delivered to the soft palate in two treatment sessions separated by 1 week at 460
      +/- 1 kHz with an energy delivery of 600 and 300 J. Snoring Score, Epworth
      Sleepiness Scale, and cephalometric analysis were measured preoperatively and
      postoperatively. Certain inflammatory laboratory parameters and visual analogue
      scale scores of symptoms were measured related to the procedure. RESULTS: The
      changes in Snoring Score and Epworth Sleepiness Scale scores were statistically
      significant. The change in the length of the soft palate was statistically
      significant, whereas the change in palatal width was not. There were no notable
      changes in the laboratory parameters. The symptom visual analogue scores were low
      and transient, resolving within days. CONCLUSIONS: The radiofrequency thermal
      ablation of the soft palate in patients with sleep-disordered breathing seems to
      be effective. It is safe and associated with only a low morbidity. The promising
      results must be confirmed in a placebo-controlled study with a larger sample size
      and a long-term follow-up.

PMID- 11224778
TI  - Modulation of myosin heavy chains in rat laryngeal muscle.
AB  - OBJECTIVES: To test the hypothesis that myosin heavy chain (MHC) composition is a
      biological marker indicative of appropriate and functional reinnervation. STUDY
      DESIGN: Age-matched adult rats were randomized for prospective study under three
      experimental conditions. METHODS: In adult rats, three experimental conditions
      were surgically created, including transient recurrent laryngeal nerve (RLN)
      crush injury, RLN transection and repair, and cricoarytenoid joint fixation with
      intact RLN. Animals were survived for 30, 90, and 180 days. At each interval,
      vocal fold mobility was assessed by rigid microlaryngoscopy. Laryngeal
      electromyography (EMG) was performed before euthanasia. The thyroarytenoid and
      posterior cricoarytenoid muscles were then excised, each muscle was processed for
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and MHC composition
      was determined. RESULTS: Thirty days after nerve crush injury, three of six
      animals regained vocal fold mobility and normal MHC composition. Impaired vocal
      fold motion in three of six animals was associated with MHC composition
      characteristic of denervation. At 90 and 180 days, normal vocal fold motion and
      normal MHC composition were observed in all animals. Following nerve transection
      and repair, impaired vocal fold motion and MHC composition characteristic of
      denervation were observed in all animals, despite evidence of reinnervation on
      EMG. Following joint fixation, alteration in MHC composition consistent with
      denervation was observed only at 30 days, as was evident in the nerve crush
      model. CONCLUSION: Temporary injury and vocal fold immobilization result in
      transient shifts in MHC composition. Nerve transection and repair result in
      persistent alteration of MHC composition and vocal fold dysfunction. The
      expression of normal MHC composition is dependent on the condition of appropriate
      neural contact and functional reinnervation.

PMID- 11224779
TI  - A prospective study on pros and cons of electrodissection tonsillectomy.
AB  - OBJECTIVE: Hemorrhages are main complications after tonsillectomy, whatever
      technique is used. This prospective study aimed at revealing pros and cons
      associated with monopolar electrodissection tonsillectomy. STUDY DESIGN: A
      prospective study. METHODS: A prospective study on all patients undergoing
      tonsillectomy or adenotonsillectomy in Central Hospital of Central Finland in
      1997. Operation time and bleeding, as well as perioperative and postoperative
      complications, were recorded. RESULTS: Inpatient tonsillectomy was performed in
      440 patients (mean age, 17.9 y). Primary post-tonsillectomy hemorrhage (within 24
      h) occurred in 2.3%. A total of 15.9% of patients searched for medical help
      because of secondary post-tonsillectomy hemorrhage, 7.7% receiving active
      treatment and 8.2% not. Post-tonsillectomy hemorrhages proved to be most common
      in older patients and when peritonsillar abscess was in patient history.
      CONCLUSIONS: Monopolar electrodissection tonsillectomy was fast and resulted in
      little intraoperative bleeding. However, postoperative hemorrhages were common,
      and the mean use of analgesics was for more than 10 days. Preoperative counseling
      must be thorough and realistic. Our results indicate that better methods for
      tonsillectomy still need to be developed.

PMID- 11224780
TI  - Endoscopic and endoscopic-assisted surgery for juvenile angiofibroma.
AB  - OBJECTIVES/HYPOTHESIS: The mainstay treatment for juvenile angiofibromas is
      surgery. Endoscopic techniques have been applied to the resection of juvenile
      angiofibromas. The aim of the study is to establish the efficacy of endoscopic
      and endoscopic-assisted techniques for the removal of juvenile angiofibromas.
      STUDY DESIGN: Retrospective review. METHODS: Retrospective review was made of all
      patients with juvenile angiofibromas who were treated with endoscopic and
      endoscopic-assisted surgery from January 1994 to July 1999. RESULTS: Fifteen
      tumors in 13 patients were removed using endoscopic or endoscopic-assisted
      surgeries. In 11 patients, endoscopic surgery or endoscopic-assisted surgery (or
      both) was successful and the patients remained without evidence of disease at a
      median follow-up of 34 months. In two patients tumor persisted, which was
      detected during routine follow-up less than 6 months after the initial surgery.
      These tumors were managed with a second endoscopic or endoscopic-assisted
      surgery, and patients remained without evidence of disease. We encountered one
      postoperative complication, a progressive optic neuropathy that was successfully
      managed with endoscopic decompression. CONCLUSIONS: Endoscopic and endoscopic
      assisted surgery is a feasible alternative or adjunct to traditional techniques.

PMID- 11224781
TI  - Esthesioneuroblastoma: the University of Iowa experience 1978-1998.
AB  - OBJECTIVE: Esthesioneuroblastoma is rare and the best treatment has yet to be
      defined. The purpose of this study is to analyze the natural history, treatment,
      and patterns of failure of esthesioneuroblastoma treated at one institution.
      METHODS: Between 1978 and 1998, 13 patients with esthesioneuroblastoma were
      identified using the University of Iowa Tumor Registry. All patients were staged
      according to Kadish criteria. Mean follow-up was 6.3 years. Six patients had 5 or
      more years of follow-up and four had follow-up exceeding 9.5 years. One patient
      was lost to follow-up at 36 months. RESULTS: No patients had Kadish stage A
      disease, five were stage B, and eight stage C. Overall actuarial 5- and 10-year
      survival rate was 61% and 24%, respectively. Disease-free survival rate at 5 and
      10 years was 56% and 42%, respectively. Seven patients have died, three of
      intercurrent disease and three of disease progression, one with an unknown
      disease status. Six patients remain alive, three without evidence of disease and
      three have experienced a local or regional recurrence. Five patients who were
      initially controlled developed recurrence, three local only, one locoregional,
      and one regional and distant. Median time to failure was 96 months. All patients
      with follow-up exceeding 12 years have experienced either a local or regional
      recurrence. Survival after salvage therapy in these patients ranged from 3 to 12
      years. CONCLUSION: Esthesioneuroblastoma has a long natural history characterized
      by frequent local or regional recurrence after conventional treatment. Successful
      retreatment can lead to prolonged survival.

PMID- 11224782
TI  - Bedside tracheostomy in the intensive care unit: a prospective randomized trial
      comparing open surgical tracheostomy with endoscopically guided percutaneous
      dilational tracheotomy.
AB  - OBJECTIVES: Objectives of the study were 1) to analyze the complication incidence
      and resource utilization of two methods of bedside tracheostomy and 2) to define
      selection criteria for bedside tracheostomy. STUDY DESIGN: Prospective randomized
      trial in the setting of a tertiary care center at a university hospital. METHODS:
      One hundred sixty-four consecutive intubated patients selected for elective
      tracheostomy were enrolled. One hundred patients met selection criteria for
      bedside tracheostomy and were randomly assigned to either open surgical
      tracheostomy (50) or endoscopically guided percutaneous dilational
      tracheotomy(50). The remaining 64 patients received open surgical tracheostomies
      in the operating room. Main outcome measures were 1) perioperative and
      postoperative complication incidence and 2) resource utilization. RESULTS:
      Patients meeting our selection criteria for bedside tracheostomy had a
      significantly reduced perioperative complication rate compared with those who
      failed to meet these criteria, and subsequently underwent tracheostomy placement
      in the operating room (5% vs. 20%, P less than or equal to.01). No statistically
      significant difference was found in the perioperative complication incidence
      between the two methods of bedside tracheostomy. However, percutaneous
      tracheostomy placement at the bedside resulted in a significant increase in
      postoperative complication incidence (16% vs. 2%, P <.05) and incurred an
      additional patient charge of $436 per bedside procedure. CONCLUSIONS: This
      investigation prospectively confirms the safety of bedside tracheostomy placement
      in properly selected patients. Complication incidence and resource utilization
      are defined for two methods of bedside tracheostomy. The results of this study
      confirm that open surgical tracheostomy represents the standard of care in
      bedside tracheostomy placement by providing a more secure airway at a markedly
      reduced patient charge. These findings will aid in the development of protocols
      and pathways for surgical airway management in critically ill patients to
      maximize cost-effective, high-quality care.

PMID- 11224783
TI  - Evaluation of eardrum laser doppler interferometry as a diagnostic tool.
AB  - OBJECTIVES: Laser Doppler interferometry (LDI) of the eardrum allows noncontact
      optical analysis of its vibrations in response to sound. Although LDI has been
      widely used in research, it has not yet been introduced into clinical practice as
      an adjunctive test for otological workup. The aim of this study was to evaluate
      LDI as a diagnostic tool in the clinical sphere. STUDY DESIGN: Prospective.
      METHODS: A measurement system was developed based on a commercially available
      scanning He-Ne laser Doppler interferometer. The study included 129 eardrums of
      79 subjects that were divided into 3 groups: 1) normal subjects and 2) patients
      with sensorineural and 3) conductive hearing loss (HL). All the patients
      suffering from conductive HL underwent ossiculoplasty, which allowed confirmation
      of the final diagnosis, and patients were assigned accordingly to the subgroups
      malleus fixation, incus luxation, and stapes fixation. RESULTS: The modified LDI
      system allowed bilateral evaluation of a subject within 30 minutes. No
      significant difference between normal subjects and patients having sensorineural
      HL were found. However, it was possible to distinguish between normal subjects
      and patients with conductive HL. Furthermore, the system had the ability to
      differentiate between various middle ear diseases. These groups differed
      statistically significantly in terms of manubrium vibration amplitude and
      resonance frequency. In malleus fixation significant differences in tympanic
      membrane movement patterns were found. CONCLUSIONS: Our LDI is applicable in
      clinical otological practice and serves as a valuable addition to the routine
      audiological investigations for preoperative evaluation of the mobility and
      integrity of the ossicular chain.

PMID- 11224784
TI  - The Nucleus Contour electrode array: a radiological and histological study.
AB  - OBJECTIVES: To evaluate the handling and insertion trauma of the recently
      developed Nucleus perimodiolar Contour electrode array (Cochlear Ltd., Pty, Lane
      Cove, New South Wales, Australia) in human temporal bones compared with the
      Nucleus standard straight electrode array. STUDY DESIGN: E-perimental control
      group. METHODS: Twenty-nine fresh-frozen bones were implanted with different
      electrode arrays by an experienced cochlear implant surgeon, and evaluated both
      radiologically and histologically. RESULTS: Intracochlear insertion of the
      standard Nucleus straight electrode array was found to be atraumatic, confirming
      previous findings in the literature. Insertion of the Nucleus Contour electrode
      array resulted in instances of localized basilar membrane penetration causing the
      electrode array to move from the scala tympani into the scala vestibuli. However,
      this trauma did not result in any observable damage to the osseous spiral lamina
      or the modiolus. Basilar membrane penetration was observed in six of eight
      cochlear bones when a standard cochleostomy size (approximately 0.8 mm) and site
      (anterior and superior to the round window) were used. However, when the surgical
      technique was modified to use a slightly larger cochleostomy ( approximately 1.8
      mm) situated closer to the round window and employ a partial stylet withdrawal
      technique during electrode insertion, the frequency of penetrations was
      restricted to two of seven bones. This trauma rate is comparable to that observed
      with other cochlear implants designs. CONCLUSIONS: Following our results, the
      design of the Nucleus Contour electrode appears to fulfill the safety
      requirements for an intracochlear electrode array, provided that the surgical
      insertion technique is modified in the manner outlined.

PMID- 11224785
TI  - Progressive sensorineural hearing loss in children with mitochondrial
      encephalomyopathies.
AB  - OBJECTIVE: Mitochondrial disorders are responsible for a variety of neurological
      syndromes. Specific mitochondrial DNA mutations have been identified recently in
      some of these rare disorders. Clinical symptoms may occur in different organs to
      various extent; often they are associated with progressive hearing loss. The aims
      of this study were to determine incidence, onset, and characteristics of hearing
      loss in children with mitochondrial encephalomyopathies and to investigate a
      possible correlation between the degree of hearing loss and neurological
      symptoms. In addition, we investigated the prognostic value of hearing loss as a
      predictor of the disease. STUDY DESIGN: From August 1992 to September 1998, 29
      patients ranging in age from 5 to 23 years (mean years) were studied. These
      children were hospitalized for diagnostic purposes in the neuropediatric
      department. METHODS: The mitochondrial disorder was diagnosed by clinical and
      laboratory testings, including analysis of the mtDNA. Audiological evaluation
      consisted of measurements of pure-tone and speech audiometry, tympanometry, and
      acoustic refle- threshold testing, auditory brainstem response, and evoked as
      well as distortion-product otoacoustic emissions. RESULTS: A sensorineural
      hearing loss was identified in 12 children. Three of these were diagnosed as
      having classic Kearns-Sayre syndrome; five as having multisystem KSS; two as
      having the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis,
      and stroke-like episodes (MELAS); one as having KSS-MELAS overlap syndrome; and
      one as having Friedreich ataxia. Longitudinal testing was performed in seven
      children, and in all of them a progression of the hearing loss could be
      demonstrated. Audiological test results in all 12 children suggested cochlear as
      well as retrocochlear origin of the hearing loss presenting independently from
      the severity of hearing impairment. No correlation between the characteristics
      and degrees of hearing loss and the number and severity of clinical neurological
      symptoms could be found. CONCLUSIONS: The present study demonstrated a high
      incidence (42%) of sensorineural hearing loss in children with mitochondrial
      encephalomyopathies. The progressive nature of the hearing impairment was
      confirmed by a significant correlation between the duration in years and severity
      of hearing loss in the children. The hearing loss does not have a prognostic
      value for the progression of the disorder. Based on our findings, we recommend
      regular audiometric examinations in patients with mitochondrial disorders.

PMID- 11224786
TI  - Variance of vestibular-evoked myogenic potentials.
AB  - OBJECTIVES/HYPOTHESIS: Vestibular-evoked myogenic potential (VEMP) has been
      thought to originate from sacculus. The variance of this potential and the
      effectiveness of the adjustments of pInII amplitudes using average muscle tonus
      of ipsilateral sternocleidomastoid muscle were evaluated. In addition, clinical
      application of VEMP was examined in patients with acoustic tumors (ATs) and
      vestibular neurolabyrinthitis (VNL). STUDY DESIGN: Prospective evaluation of the
      VEMP in 18 normal volunteers and 6 patients. METHODS: Variance and left-right
      difference of each parameter, including pI latency, nII latency, pInII amplitude,
      and threshold, was analyzed. Input-output function of pInII amplitude was
      evaluated. Average muscle tonus was calculated in 20 ears and applied for
      adjustment of pInII amplitude. Sensitivity of each parameter of VEMP was examined
      in 3 patients with ATs and 3 patients with VNL. RESULTS: VEMP was present in all
      36 ears of 18 control subjects. Thresholds of VEMP for normal subjects were 80 to
      95 dB normal hearing level (nHL). The muscle tonus affected pInII amplitude
      significantly; however, no statistically significant improvement was observed in
      test-retest investigation after adjustment using muscle tonus. The threshold of
      the affected side was elevated compared with the non-affected side in all
      patients with ATs, whereas 2 of 3 patients showed normal pInII-ratio. One patient
      with VNL presented normal VEMP, whereas 2 patients presented no VEMP to the
      highest stimulus intensity. CONCLUSIONS: Interaural difference of thresholds
      might be the most useful parameters. Adjustment using average muscle tonus is not
      necessary when the subject is able to get sufficient muscle tonus.

PMID- 11224787
TI  - The expression of apoptosis-related proteins in the aged cochlea of Mongolian
      gerbils.
AB  - OBJECTIVE: Apoptotic changes have been reported in the aged gerbil cochlea and
      are speculated to be one of the principal causes of presbyacusis. The objective
      of the study was to determine the underlying mechanism of apoptotic change in the
      aged gerbil cochlea. STUDY DESIGN: Prospective controlled animal study. METHODS:
      We examined the tissue distribution of bcl-2, bax, caspase-3p20, and caspase-3p32
      using immunohistochemical techniques in the young and aged gerbil cochlea,
      together with the measurement of the distortion product of otoacoustic emission
      (DPOAE). RESULTS: Aged gerbils showed a significant reduction of the DPOAE
      amplitude as compared with that of the young gerbils, suggesting a disturbance of
      the auditory function in the aged cochlea. There was a significant decrease in
      the number of bcl-2-positive cells in the aged gerbils. The expression of bax in
      the aged group was slightly increased but did not significantly differ from that
      in the young gerbils. A significantly increased number of caspase-3p20-positive
      cells was observed in the organ of Corti, spiral ganglion, and lateral wall of
      cochlea in the aged gerbils as compared with those of the young gerbils. There
      was no significant difference in the expression levels of caspase-3p32 between
      the young and aged groups. In the aged cochlea, the degree of deterioration of
      DPOAE responses was compatible with those of both the reduction of bcl-2 and the
      activation of caspase-3p20. CONCLUSION: These data suggest that the suppression
      of bcl-2 protein expression may lead to apoptosis-induced presbyacusis through
      activation of caspase-3 in the aged gerbil cochlea.

PMID- 11224788
TI  - Expression of p75NTR and its associated protein NADE in the rat cochlea.
AB  - OBJECTIVES/HYPOTHESIS: To investigate the expression of the low-affinity
      neurotrophin receptor p75 (p75NTR) and its associated protein NADE in the cochlea
      of the developing and the adult rat. Studies such as this one will help to
      predict the functional role of p75NTR and NADE in cochlear development. STUDY
      DESIGN: Histochemical evaluation of p75NTR and NADE in the rat cochlea was
      performed. METHODS: Immunohistochemical analysis was used to localize p75NTR and
      NADE in the rat cochlea at postnatal (PN) days PN0, PN2, PN4, PN6, PN8, PN10, and
      PN13 and in the adult. Confocal laser scanning microscopy was used to analyze
      whole-mount specimens. RESULTS: Immunoreactivity of both p75NTR and NADE was
      observed in pillar cells. However, these proteins displayed reciprocal expression
      patterns. Expression of p75NTR was detected at PN0 and PN2, but disappeared after
      PN4. In contrast, NADE expression was initially detected at PN2 and persisted
      into adulthood. CONCLUSIONS: The neurotrophin receptor p75NTR and NADE have
      distinct and independent roles in developing and mature cochlea.

PMID- 11224789
TI  - A new technique for the insertion of a silastic button for septal perforations.

PMID- 11224790
TI  - Management of cranial defects after frontal osteoplastic flap.

PMID- 11224791
TI  - Hypopharyngeal reconstruction using pectoralis major myocutaneous flap and pre
      vertebral fascia.

PMID- 11224792
TI  - Prosthetic management of pharyngocutaneous fistula by means of a salivary
      conduit.

PMID- 11224793
TI  - Anti-heat shock protein 70 antibodies in Meniere's disease.

PMID- 11224794
TI  - Effect of swim taper on whole muscle and single muscle fiber contractile
      properties.
AB  - TRAPPE, S., D. COSTILL, and R. THOMAS. Effect of swim taper on whole muscle and
      single muscle fiber contractile properties. Med. Sci. Sports Exerc., Vol. 32, No.
      12, 2000, pp. 48-56. Purpose: To examine the changes in whole muscle function and
      single cell contractile properties of Type I and II muscle fibers from the
      deltoid muscle of highly trained swimmers before and after a 21-d reduction in
      training volume (taper). Methods: Six college male swimmers (age, 20 +/- 1 yr;
      height, 187 +/- 2 cm, weight, 79 +/- 3 kg, fat, 7 +/- 1%) who had been, on
      average, swimming 6200 m.d-1 for 5 months before the taper participated in this
      investigation. Results: Whole muscle power increased (P < 0.05) 17% and 13% on
      the swim bench and swim power tests, respectively. Swim times improved by 4%
      (range: 3.0-4.7%; P < 0.05). There was no change in Type I fiber diameter,
      whereas Type IIa fibers were 11% larger (P < 0.05) after taper. Peak force (Po)
      of the Type I fibers was unaffected by the taper but increased (P < 0.05) from
      0.63 +/- 0.02 to 0.82 +/- 0.05 mN in the IIa fibers. However, the specific force
      (Po/CSA) of the IIa fibers was unchanged. Shortening velocity (Vo) was 32% and
      67% faster (P < 0.05) in the Type I and IIa fibers, respectively. Although Type I
      fiber power was unaltered, the IIa fibers increased 2.5-fold from 24.6 +/- 2.8 to
      56.2 +/- 3.9 uN.FL.s-1. When power was normalized for cell size, the power was
      still elevated twofold. Conclusions: These data suggest that tapering induces
      alterations in the contractile properties of single muscle fibers. Further, it
      appears that the Type IIa fibers are more affected than the Type I fibers by the
      taper. The increased size, strength, velocity, and power of the IIa fibers may be
      responsible for the improvements in whole muscle strength and power after the
      taper.

PMID- 11224802
TI  - Factors influencing sport participation among athletes with spinal cord injury.
AB  - OBJECTIVE: This exploratory study examined the relationships between pre- and
      post-injury sport participation among active individuals with spinal cord injury
      (SCI) in the United Kingdom. In particular, factors that influence individuals
      with SCI into sport were identified. METHODS: A total of 143 British individuals
      with SCI currently participating in wheelchair basketball, wheelchair rugby,
      wheelchair tennis, and wheelchair athletics were recruited. A total of 112
      subjects were active prelesion, and 31 subjects were inactive preinjury. A
      Disability Sport Participation questionnaire developed by the authors was used
      for data collection. The questionnaire was distributed through the British
      Wheelchair Sport Associations. Personal, impairment, health and fitness,
      socialization, and participation data of athletes with SCI were collected. Groups
      of active preinjury and inactive preinjury were compared. RESULTS: For athletes
      who had been active pre-SCI, the in-hospital rehabilitation program and
      specialized sport club for people with disabilities were more important contexts
      for introducing the sport after injury to individuals. Friends and peers with
      disabilities were much more influential as initial and continuing socialization
      agents than rehabilitation therapists. The main reasons for athletes with SCI who
      participated in sports after injury were for fitness, fun, health, and
      competition, although many athletes noted that social aspects and rehabilitation
      also influenced their sport participation. CONCLUSION: This study identified
      social contexts, social agents, difficulties, sources of information, and reasons
      for sport participation of athletes with SCI. The results may offer some
      directions for the improvement of rehabilitation programs for people with SCI and
      also help the development of appropriate strategies to encourage people with SCI
      to participate in sports and leisure activities.

PMID- 11224803
TI  - Creatine supplementation and health variables: a retrospective study.
AB  - PURPOSE: Long-term safety of creatine supplementation has been questioned. This
      retrospective study was performed to examine markers related to health, the
      incidence of reported side effects and the perceived training benefits in
      athletes supplementing with creatine monohydrate. METHODS: Twenty-six athletes
      (18 M and 8 F, 24.7 +/- 9.2 y; 82.4 +/- 20.0 kg; 176.5 +/- 8.8 cm) from various
      sports were used as subjects. Blood was collected between 7:00 and 8:30 a.m.
      after a 12-h fast. Standard clinical examination was performed for CBC and 27
      blood chemistries. Testosterone, cortisol, and growth hormone were analyzed using
      an ELISA. Subjects answered a questionnaire on dietary habits, creatine
      supplementation, medical history, training history, and perceived effects of
      supplementation. Body mass was measured using a medical scale, body composition
      was estimated using skinfolds, and resting heart rate and blood pressure were
      recorded. Subjects were grouped by supplementation length or no use: Gp1
      (control) = no use (N = 7; 3 F, 4 M); Gp2 = 0.8-1.0 yr (N = 9; 2 F, 7 M); and Gp3
      = 1(+) (N = 10; 3 F, 7 M). RESULTS: Creatine supplementation ranged from 0.8--4
      yr. Mean loading dose for Gp2 and Gp3 was 13.7 +/- 10.0 and the maintenance dose
      was 9.7 +/- 5.7 g.d(-)1. Group differences were analyzed using one-way ANOVA.
      CONCLUSIONS: Expected gender differences were observed. Of the comparisons made
      among supplementation groups, only two differences for creatinine and total
      protein (P < 0.05) were noted. All group means fell within normal clinical
      ranges. There were no differences in the reported incidence of muscle injury,
      cramps, or other side effects. These data suggest that long-term creatine
      supplementation does not result in adverse health effects.

PMID- 11224804
TI  - Left ventricular wall motion during diastolic filling in endurance-trained
      athletes.
AB  - PURPOSE: The purpose of this study was to assess left ventricular (LV) wall
      motion in highly endurance-trained athletes to evaluate LV diastolic function in
      physiologically hypertrophied hearts. BACKGROUND: Diastolic filling dynamics have
      previously been examined in endurance-trained athletes by measuring pulsed-wave
      mitral inflow velocities during the early and atrial filling phase, indicating an
      unimpaired LV function. Assessment of LV wall motion may give additional
      information about the LV diastolic function in endurance-trained athletes.
      METHODS: Left ventricular mass (LVM) and volume (LVV) were determined by M-mode
      echocardiography. Peak LV wall motion in the region of the basal septum close to
      the mitral anulus were measured during the early rapid and atrial filling phase
      by tissue Doppler in 30 endurance-trained athletes (T) and 16 sedentary control
      subjects (C) presumed to be healthy. RESULTS: Myocardial LVM and LVV in T (LVM
      159.4 +/- 18.0 g.m(-2), LVV 100.4 +/- 13.0 mL.m(-2)) were significantly higher
      than in C (LVM 105.7 +/- 12.0.m(-2), LVV 70.1 +/- 11.9 mL.m(-2)), and heart rate
      (HR) was significantly lower (HR C: 69.6 +/- 11.0 bpm, T 50.9 +/- 8.7 bpm),which
      is consistent with endurance training (P < 0.01 for both). Peak LV wall motion
      during the early rapid filling phase did not differ significantly between the
      groups (T: 10.69 +/- 1.46 cm.(s-)1; C: 10.61 +/- 1.52 cm.(s-)1). Peak atrial wall
      motion was significantly lower in T (4.53 +/- 0.84 cm.s-1) versus C (5.74 +/-
      0.75 cm.s(-1)), and the ratio of peak early diastolic to atrial wall motion was
      consequently higher in athletes (P < 0.01 for both). CONCLUSION: Regional wall
      motion at the basal septum near the mitral anulus during the early rapid filling
      phase is not altered by an increase in LVM or LVV when associated with endurance
      training.

PMID- 11224805
TI  - The effects of eccentric velocity on activation of elbow flexors: evaluation by
      magnetic resonance imaging.
AB  - PURPOSE: To compare magnetic resonance imaging (MRI) signal intensity changes in
      the primary elbow flexors during two isotonic exercise protocols varying in
      eccentric velocity and the ratio of eccentric to concentric activity. METHODS:
      Twelve men performed two exercise protocols. The right and left arms were
      randomly assigned to one of two protocols that had the same workload (60% 1RM)
      and same total time of exercise (144 s) but differed in the velocity and ratio of
      eccentric to concentric activity (1:1 and 5:1 for the fast and slow protocols,
      respectively). MRI signal intensity changes were quantified pre- and post
      exercises using an inversion recovery sequence with a 1.5T MRI system (TR = 2500
      ms, TE = 90 ms, TI = 140 ms). Percent change in MRI signal intensity, rate of
      perceived exertion (RPE), and delayed onset muscle soreness (DOMS) were recorded
      and analyzed. RESULTS: The biceps brachii was found to be preferentially
      recruited during the fast protocol compared with the brachialis, whereas the
      brachialis was found to be preferentially recruited during the slow protocol (P <
      0.05). The fast exercise protocol was perceived as being more strenuous (RPE =
      8.3 +/- 2.1) than the slow (RPE = 5.4 +/- 1.5, P < 0.05) and produced DOMS in 58%
      of the tested subjects. CONCLUSIONS: These results suggest that agonists respond
      to various loading conditions nonhomogeneously. These findings may have
      implications with respect to exercise prescriptions for specific muscles.

PMID- 11224806
TI  - Injury patterns among female field hockey players.
AB  - PURPOSE: To examine injury patterns among female field hockey players and to
      broaden the current base of knowledge by identifying the injury rates of
      different playing positions. It was hypothesized that goalkeepers would have the
      highest rate of injury, followed by forwards. METHODS: High school, university,
      and national level female field hockey players (N = 158) completed an anonymous
      questionnaire. They reported personal characteristics (age, height, weight);
      field hockey information (level, years of experience, surface); injury history
      (type, site, cause, severity); and back pain information. Injury rates were
      calculated per athlete-year. RESULTS: The most frequently injured site of the
      body was the lower limb (51%), followed by the head/face (34%), upper limb (14%),
      and torso (1%). The most prevalent types of injuries were ankle sprains, followed
      by hand fractures and head/face injuries. Goalkeepers had the highest rate of
      injury (0.58 injuries/athlete-year), whereas midfielders were the most injured
      field players (0.36 injuries/athlete-year). Back pain was reported by 59% of the
      sample, and the lower back was the most common site of this pain. CONCLUSION:
      There are differences in the rates of injury among playing positions in field
      hockey and in the types of acute injury sustained at each position. The high
      number of injuries to the head and face region is also cause for concern.
      Although most of these injuries are minor, the serious injuries that do occur can
      be very severe. Now that these patterns have been identified, further examination
      of the playing situations that lead to injury should be undertaken.

PMID- 11224807
TI  - Self-reported symptoms and exercise-induced asthma in the elite athlete.
AB  - PURPOSE: The purpose of this study was to compare self-reported symptoms for
      exercise-induced asthma (EIA) to postexercise challenge pulmonary function test
      results in elite athletes. METHODS: Elite athletes (N = 158; 83 men and 75 women;
      age: 22 +/- 4.4 yr) performed pre- and post-exercise spirometry and were grouped
      according to postexercise pulmonary function decrements (PFT-positive, PFT
      borderline, and PFT-normal for EIA). Before the sport/environment specific
      exercise challenge, subjects completed an EIA symptoms-specific questionnaire.
      RESULTS: Resting FEV1 values were above predicted values (114--121%) and not
      different between groups. Twenty-six percent of the study population demonstrated
      >10% postexercise drop in FEV1 and 29% reported two or more symptoms. However,
      the proportion of PFT-positive and PFT-normal athletes reporting two or more
      symptoms was not different (39% vs. 41%). Postrace cough was the most reported
      symptom, reported significantly more frequently for PFT-positive athletes (P <
      0.05). Sensitivity/specificity analysis demonstrated a lack of effectiveness of
      self-reported symptoms to identify PFT-positive or exclude PFT-normal athletes.
      Postexercise lower limit reference ranges (MN-2SDs) were determined from normal
      athletes for FEV1, FEF25--75% and PEF to be -7%, -12.5%, and -18%, respectively.
      CONCLUSION: Although questionnaires provide reasonable estimates of EIA
      prevalence among elite cold-weather athletes, the use of self-reported symptoms
      for EIA diagnosis in this population will likely yield high frequencies of both
      false positive and false negative results. Diagnosis should include spirometry
      using an exercise/environment specific challenge in combination with the
      athlete's history of asthma symptoms.

PMID- 11224808
TI  - Fibrinolytic response to acute exercise in patients with peripheral arterial
      disease.
AB  - PURPOSE: Elevations in tissue plasminogen activator (tPA) are postulated to
      protect against atherothrombotic events during exercise. However, fibrinolytic
      response to repetitive bouts of symptom-limited exercise is unknown in peripheral
      arterial disease (PAD) patients, a population with impaired fibrinolysis and
      increased risk for ischemic events. The purpose of the present study was to
      evaluate the fibrinolytic response to repetitive bouts of symptom-limited
      exercise in PAD patients. METHODS: Nine (8 male, 1 female) patients with Fontaine
      State II PAD were studied. Fasting blood samples for determination of tPA and
      plasminogen activator inhibitor (PAI-1) were obtained into an acidified citrate
      solution via an indwelling venous catheter before, immediately after, 30 min
      after, and 60 min after submaximal treadmill walking. Patients walked
      intermittently at 65% of maximal intensity achieved on a previous graded exercise
      test until 30 min of exercise was achieved. RESULTS: Exercise increased tPA
      activity by 180% (0.5 +/- 0.16 IU.mL(-1) baseline, 1.4 +/- 1.2 IU.mL(-1)
      postexercise), and decreased PAI-1 activity by 40% (20.6 +/- 5.5 AU.mL(-1)
      baseline, 11.8 +/- 6.2 AU.mL(-1) postexercise), without changing tPA or PAI-1
      antigen. Notably, plasma tPA activity levels 1 h after exercise remained elevated
      by 80%, whereas PAI-1 activity remained decreased by 49%. The decrease in PAI-1
      significantly (P < 0.05) correlated with oxygen uptake (VO(2)) during submaximal
      exercise (r = -0.77). CONCLUSION: These findings demonstrate that repetitive
      bouts of symptom-limited exercise produce a substantial improvement in the
      fibrinolytic profile of PAD patients, which persists at least 1 h after exercise
      cessation.

PMID- 11224809
TI  - Muscle function in 164 men and women aged 20--84 yr.
AB  - PURPOSE: The purpose of the present study was to investigate the effect of aging
      in men and women on muscle functional properties, i.e., muscle force and force
      per unit of cross-sectional area (force/CSA). METHODS: A total of 164 volunteers
      participated in this study and were divided into five groups according to their
      chronological age as follows: 20s (20--39 yr old), 40s, 50s, 60s, and 70s (70--84
      yr old). Isokinetic (0, 60, 180, and 300 degrees.s(-1)) knee extensor and flexor
      peak torque, and CSA of the quadriceps femoris (QF) muscle of the mid-thigh were
      measured. RESULTS: Peak torque during knee extension and flexion was inversely
      related to age in both men and women. This was the case irrespective of the speed
      of contraction in both genders (men: r = -0.797 to -0.756, all P < 0.001, women:
      r = -0.639 to -0.530, all P < 0.001). A significant correlation was observed
      between CSA of QF and peak torque during isometric knee extension in men (r =
      0.827, P < 0.001) and women (r = 0.657, P < 0.001). During isometric contraction,
      the force/CSA exhibited a significant decrease with increasing age in men (r = 
      0.518, P < 0.001) but not in women (r = -0.207, NS). CONCLUSION: These results
      thus suggest that muscle strength losses would be mainly due to a decline in
      muscle mass in both genders, whereas age-related decline in muscle function in
      men may also be the result of neural factors, such as muscle recruitment and/or
      specific tension.

PMID- 11224810
TI  - Effect of intense training on plasma leptin in male and female swimmers.
AB  - PURPOSE: The purpose of this study was to determine whether fasting plasma leptin
      concentration was altered with an increase in training volume in competitive male
      and female athletes. METHODS: Intercollegiate male (N = 9) and female (N = 12)
      swimmers were examined during the preseason and at two times during the mid
      season (mid-season 1 and mid-season 2) when training volume was relatively high
      (33,000 m.wk(-1)). Body composition (hydrostatic weighing), energy intake and
      expenditure, and fasting plasma leptin concentration were measured. RESULTS: In
      the women, there was a significant (P < 0.05) decline in fat mass (2 kg) with the
      increase in training volume, which was not accompanied by a reduction in fasting
      leptin (12.8 +/- 1.5 vs 11.0 +/- 1.2 vs 11.0 +/- 1.5 ng.mL(-1) for preseason, mid
      season 1, and mid-season 2, respectively). In the men, there were no significant
      changes in body composition, body mass, or fasting leptin (4.4 +/- 0.8 vs 4.3 +/-
      0.8 vs 4.6 +/- 0.8 ng.mL(-1), respectively). CONCLUSION: These findings suggest
      1) plasma leptin is not sensitive to an increase in training volume and 2) leptin
      may not be indicative of changes in fat mass with an increase in training volume
      in female athletes. These data suggest that leptin may not be useful in
      monitoring relative training stress in athletes.

PMID- 11224811
TI  - Hemoglobin/myoglobin oxygen desaturation during Alpine skiing.
AB  - PURPOSE: To investigate muscle blood volume (BV) change and hemoglobin/myoglobin
      oxygen desaturation (OD) during simulated giant slalom (GS) and slalom (SL)
      Alpine ski racing. METHODS: Joint angle, BV, OD, and heart rate (HR) were
      evaluated during GS and SL events in 30 junior elite skiers ages 9--17 yr (13.5
      +/- 2.3). Subjects were stratified by ski class and age: group I, J1 and J2, ages
      15--18 yr (16.8 +/- 0.8); group II, J3, 13--14 yr (13.6 +/- 0.7); and group III,
      J4 and J5, 9--12 yr (11.5 +/- 1.2). Near-infrared spectrophotometry (NIRS) was
      used to measure BV and OD in the capillary bed of the vastus lateralis during
      trials. Maximal OD was determined during thigh cuff ischemia (CI). Quadriceps
      cross-sectional area (CSA) was estimated by skin-fold and thigh circumference.
      RESULTS: Joint angles were smaller (P < 0.05) during GS than SL for ankle (83.8
      +/- 11.9 degrees; 98.6 +/- 15.7 degrees ), knee (107.4 +/- 14.9 degrees; 118.3 +/
      18.0 degrees ), and hip (98.8 +/- 14.3 degrees; 107.5 +/- 16.2 degrees ). BV
      reduction from rest to peak exercise (Delta BV) was 30% greater (P < 0.05) during
      the GS than SL, whereas Delta OD was 33% greater (P < 0.05) during GS. Delta OD,
      relative to CI OD, was greater for all subjects during GS (79.2 +/- 3.7%) than SL
      (65.7 +/- 4.4%). This pattern continued within groups; group II displayed the
      greatest relative desaturation (82.9 +/- 7.6%). CSA was larger in older skiers
      (92.5 +/- 21.6; 72.5 +/- 12.3; 65.3 +/- 21.2 cm(2)) and correlated with Delta OD
      (P < 0.05). CONCLUSION: The larger reduction in BV (Delta BV change) and greater
      OD when skiers assumed lower posture during GS than SL may be related to greater
      effective static load secondary to higher percent of maximal voluntary
      contraction and is consistent with compromised blood flow to working muscle.

PMID- 11224812
TI  - Relationship between leucine oxidation and oxygen consumption during steady-state
      exercise.
AB  - PURPOSE: The purpose of this study was to assess the relationship between whole
      body leucine oxidation and oxygen consumption during steady-state exercise. Our
      hypothesis was that leucine oxidation will be responsive to increased whole-body
      energy needs. METHODS: Sixteen healthy individuals (7 women and 9 men) were
      infused with a stable isotope of leucine and, for comparison purposes, lysine
      during 60 min of moderate-intensity exercise. RESULTS: Leucine oxidation was
      increased (P < 0.05) and nonoxidative leucine disposal was decreased (P < 0.05),
      whereas leucine and lysine rate of appearance remained unchanged (P = NS) during
      exercise. Linear regression analysis indicated a modest relationship between
      leucine oxidation and steady-state oxygen consumption (R = 0.69; P < 0.003)
      during steady-state exercise. The coefficient of determination (R(2) = 0.49)
      indicates that approximately half of the variance in whole-body leucine oxidation
      during exercise can be explained by whole-body oxygen consumption. CONCLUSION: In
      a statistically appropriate sample size of humans whose dietary intake was
      controlled, the whole-body rate of leucine oxidation during exercise was only
      partially influenced by energy demands.

PMID- 11224813
TI  - Alterations in intracellular calcium signaling of lymphocytes after exhaustive
      exercise.
AB  - PURPOSE: Exhaustive exercise is accompanied by pronounced quantitative changes in
      leukocytes. Whereas most studies on lymphocytes have concentrated on their
      proliferative responses or cytokine secretion, not much is known about exercise
      induced changes in intracellular signal transduction processes. In lymphocytes,
      the concentration of intracellular free calcium ([Ca(2+)](i)) is an important
      intracellular second messenger linking extracellular stimuli to cellular
      responses. The aim of the present study was to examine the effect of exhaustive
      exercise on the calcium homeostasis of lymphocytes. METHODS: Healthy volunteers
      underwent treadmill exercise at 80% of their maximal oxygen uptake until
      exhaustion. Blood samples were taken before, immediately after, 1 h after, and 1
      d after the test. Lymphocyte subsets were analyzed by flow cytometry; isolation
      of lymphocytes was performed by density gradient centrifugation. [Ca(2+)](i) was
      measured using the calcium-sensitive fluorescent dye Fura-2. RESULTS: Compared
      with preexercise conditions, basal [Ca(2+)](i) was increased immediately after
      exercise, whereas there was no change after 1 h or 1 d. The anti-CD3- and
      phytohemagglutinin-induced Ca(2+) responses demonstrated a bivalent pattern.
      Immediately after exercise, Ca(2+) transients were impaired, whereas 1 h after
      and 1 d after the test, the Ca(2+) responses were increased. In contrast, the
      Ca(2+) responses induced by thapsigargin were not different at any time interval.
      Lymphocyte subsets increased immediately after exercise, especially natural
      killer cells and CD8+ T cells, and decreased below preexercise levels after 1 h.
      One day after exercise, cell counts were not different from preexercise levels.
      CONCLUSIONS: Taken together, this novel approach demonstrates that exhaustive
      exercise has a profound influence on intracellular calcium signaling of
      lymphocytes. These effects may explain changes in lymphocyte function that have
      previously been reported.

PMID- 11224814
TI  - Fluid shifts resulting from exercise in rats as detected by bioelectrical
      impedance.
AB  - PURPOSE: This study was designed to investigate the immediate effect of exercise
      intensity and duration on body fluid volumes in rats throughout a 3-wk exercise
      program. METHODS: Changes in the extracellular water (ECW) and total body water
      (TBW) volumes of rats were measured preexercise and postexercise using multiple
      frequency bioelectrical impedance analysis. Groups of rats were exercised at two
      intensities (6 m.min(-1) and 12 m.min(-1)) for two exercise times (60 min and 90
      min) 5 d.wk(-1) during a 3-wk period. Changes in plasma electrolytes, glucose,
      and lactate resulting from the exercise were also measured on 3 d of each week.
      RESULTS: Each group of animals showed significant losses in ECW and TBW as a
      direct result of daily exercise. The magnitude of fluid loss was directly related
      to the intensity of the exercise, but not to exercise duration; although the
      magnitude of daily fluid loss at the higher intensity exercise (12 m.min(-1))
      decreased as the study progressed, possibly indicating a training effect.
      CONCLUSION: At low-intensity exercise, there is a small but significant loss in
      both TBW and ECW fluids, and the magnitude of these losses does not change
      throughout a 3-wk exercise program. At moderate levels of exercise intensity,
      there is a greater loss of both TBW and ECW fluids. However, the magnitudes of
      these losses decrease significantly during the 3-wk exercise program, thus
      demonstrating a training effect.

PMID- 11224815
TI  - Age-related differences in physical activity levels of young adults.
AB  - PURPOSE: To examine age-related differences in the physical activity behaviors of
      young adults. METHODS: We examined rates of participation in vigorous- and
      moderate-intensity leisure-time activity and walking, as well as an index of
      physical activity sufficient for health benefits in three Australian cross
      sectional samples, for the age ranges of 18--19, 20--24, and 25--29 yr. Data were
      collected in 1991, 1996, and 1997/8. RESULTS: There was at least a 15% difference
      in vigorous-intensity leisure-time physical activity from the 18--19 yr to the 25
      -29 yr age groups, and at least a 10% difference in moderate-intensity leisure
      time physical activity. For the index of sufficient activity there was a
      difference between 9 and 21% across age groups. Differences in rates of walking
      were less than 8%. For all age groups, males had higher rates of participation
      for vigorous and moderate-intensity activity than did females, but females had
      much higher rates of participation in walking than males. Age-associated
      differences in activity levels were more apparent for males. CONCLUSIONS:
      Promoting walking and various forms of moderate-intensity physical activities to
      young adult males, and encouraging young adult females to adopt other forms of
      moderate-intensity activity to complement walking may help to ameliorate
      decreases in physical activity over the adult lifespan.

PMID- 11224816
TI  - Resistance training combined with bench-step aerobics enhances women's health
      profile.
AB  - PURPOSE: The purpose of this study was to investigate the comprehensive
      physiological alterations that take place during the combination of bench-step
      aerobics (BSA) and resistance exercise training. METHODS: Thirty-five healthy,
      active women were randomly assigned to one of four groups that either a)
      performed 25 min of BSA only (SA25); b) performed a combination of 25 min of BSA
      and a multiple-set upper and lower body resistance exercise program (SAR); c)
      performed 40 min of BSA only (SA40); or d) served as a control group (C), only
      performing activities of daily living. Direct assessments for body composition,
      aerobic fitness, muscular strength, endurance, power, and cross-sectional area
      were performed 1 wk before and after 12 wk of training. RESULTS: All training
      groups significantly improved peak VO(2) (3.7 to 5.3 mL O(2).kg(-1).min(-1)),
      with the greatest improvement observed in the SAR group (P = 0.05). Significant
      reductions in preexercise heart rates (8-9 bpm) and body fat percent (5--6%) were
      observed in all training groups after training. Significant reductions in resting
      diastolic blood pressure were observed for the SAR and SA40 groups (6.7 and 5.8
      mm Hg, respectively). Muscular strength and endurance only improved significantly
      in the SAR group (21 and 11% respectively). All groups demonstrated increased
      lower body power (11--14%), but only the SAR group significantly improved upper
      body power (32%). Thigh muscle cross-sectional areas measured via magnetic
      resonance imaging (MRI) increased primarily for the SAR group. CONCLUSION: BSA is
      an exercise modality effective for improving physical fitness and body
      composition in healthy women. The addition of resistance exercise appears to
      enhance the total fitness profile by improving muscular performances, muscle
      morphology, and cardiovascular fitness greater than from performing BSA alone.
      Therefore, the inclusion of both modalities to an exercise program is most
      effective for improving total body fitness and a woman's health profile.

PMID- 11224817
TI  - Fitness, fatness, and coronary heart disease risk in adolescents: the Northern
      Ireland Young Hearts Project.
AB  - PURPOSE: The purpose of this study was to examine the independence and relative
      strengths of association between coronary heart disease (CHD) risk status and
      both body fatness and cardiorespiratory (C-R) fitness in 12- and 15-yr-old
      adolescents. METHODS: The study cohort consisted of 1015 schoolchildren aged 12
      and 15 yr (251 12-yr-old boys, 258 12-yr-old girls, 252 15-yr-old boys, and 254
      15-yr-old girls), representing a 2% random sample of each population group. For
      each child, height, weight, sexual maturity (pubertal status), skin-fold
      thicknesses (4 sites), blood pressure (random zero sphygmomanometer), nonfasting
      serum total, and high density lipoprotein (HDL)-cholesterol and C-R fitness (20-m
      shuttle run; 20-MST) were determined under standardized conditions. Socioeconomic
      status and habitual physical activity were also determined from questionnaire
      information. Multiple regression analyses were carried out to examine
      relationships between five CHD risk factors, and fitness and fatness and to
      examine the relative strengths of fitness and fatness on CHD risk status,
      correcting for potential confounding variables. RESULTS: Our main findings were:
      1) Relationships between fatness and CHD risk factors are invariably stronger
      than between fitness and the same risk factors. For example, partially adjusted
      standardized regression coefficients for 12-yr-old boys revealed significant
      relationships between all five CHD risk factors and fatness, compared with three
      of five for fitness. The corresponding figures for 12-yr-old girls were three of
      five (fatness) and one of five (fitness). Broadly similar results were apparent
      for 15-yr-olds. 2) Although relationships between fitness and CHD risk factors do
      not survive further adjustment for fatness, the relationships between fatness and
      CHD risk are more robust and are unaffected by further adjustment for fitness.
      CONCLUSION: Our results indicate that the observed relationships between C-R
      fitness and CHD risk status in adolescents are mediated by fatness, whereas the
      observed relationships with fatness are independent of fitness. Primary
      prevention of CHD during childhood should therefore concentrate upon preventing
      or reversing undue weight gain.

PMID- 11224818
TI  - Physical activity assessed by activity monitor and doubly labeled water in
      children.
AB  - PURPOSE: To validate the Computer Science and Application's (CSA) activity
      monitor for assessment of the total amount of physical activity during two school
      weeks in 9-yr-old children and to develop equations to predict total energy
      expenditure (TEE) and activity energy expenditure (AEE) from activity counts and
      anthropometric variables. METHODS: A total of 26 children (15 boys and 11 girls,
      mean age 9.1 +/- 0.3 yr) were monitored for 14 consecutive days. TEE was
      simultaneously measured by the doubly labeled water method. Averaged activity
      counts (counts.min(-1)) were compared with data on: 1) TEE, 2) AEE = TEE minus
      basal metabolic rate (BMR; estimated from predictive equations), and 3) daily
      physical activity level (PAL = TEE/BMR). RESULTS: Physical activity determined by
      activity counts was significantly related to the data on energy expenditures: TEE
      (r = 0.39; P < 0.05), AEE (r = 0.54; P < 0.01), and PAL (r = 0.58; P < 0.01).
      Multiple stepwise regression analysis showed that TEE was significantly
      influenced by gender, body composition (body weight or fat free mass), and
      activity counts (R(2) = 0.54--0.60). AEE was significantly influenced by activity
      counts and gender (R(2) = 0.45). There were no significant differences between
      activity counts and PAL in discriminating among activity levels with "low" (PAL <
      1.56), "moderate" (1.57 < or = PAL > or = 1.81), and "high" (PAL > 1.81)
      intensity. CONCLUSION: Activity counts from the CSA activity monitor seems to be
      a useful measure of the total amount of physical activity in 9-yr-old children.
      Activity counts contributed significantly to the explained variation in TEE and
      was the best predictor of AEE.

PMID- 11224819
TI  - Effect of isometric exercise on pain perception and blood pressure in men and
      women.
AB  - PURPOSE: To examine the influence of isometric handgrip exercise (ISO EX) on pain
      perception and blood pressure in men and women. METHODS: Fifteen men and 16 women
      completed max and submax ISO EX consisting of squeezing a hand dynamometer with
      the right hand as hard as possible for the max session, and squeezing between 40%
      and 50% of max for 2 min for the submax session. Pain thresholds (PT), pain
      ratings (PR), blood pressure (SBP and DBP), and heart rate (HR) were assessed
      while a noxious pressure stimulus was applied to the right forefinger for 2 min
      before and after ISO EX. Data were analyzed with a 2 (gender) x 2 (trials) ANOVA.
      RESULTS: Results indicated a significant trials effect and a significant gender
      by trials interaction (P < 0.05) for PT for the max and submax sessions. Women
      had lower PT before ISO EX in comparison with the men. In addition, PT for the
      women increased significantly after ISO EX but did not change for the men. There
      were significant gender and trials effects (P < 0.05) for SBP for the submax
      session. Women had lower SBP before ISO EX, and SBP increased after ISO EX. DBP
      was also found to be lower (P < 0.05) in women before max and submax ISO EX, with
      DBP increasing after submax ISO EX in men and women. PR were found to be lower
      after max ISO EX in men and women, whereas PR were found to be lower in women
      after submax ISO EX. CONCLUSION: It is concluded that: 1) men and women differed
      in PT, SBP, and DBP before ISO EX; and 2) analgesia after ISO EX is observed more
      consistently in women.

PMID- 11224820
TI  - Monitoring the lactate threshold in world-ranked swimmers.
AB  - PURPOSE: To determine whether lactate profiling could detect changes in discrete
      aspects of endurance fitness in world-ranked swimmers during a season. METHODS:
      Eight male and four female Australian National Team swimmers aged 20--27 yr
      undertook a 7 x 200-m incremental swimming step test on four occasions over an 8
      month period before the 1998 Commonwealth Games (CG): January (10 d before the
      World Championships), May (early-season camp), July (midseason), and August (16 d
      before the CG). The lactate threshold (LT) was determined by a mathematical
      formula that calculated the threshold as a function of the slope and y-intercept
      of the lactate-velocity curve. RESULTS: Maximal 200-m test time declined
      initially from 127.7 +/- 4.2 s (January 1998) to 130.2 +/- 4.5 s (May 1998) and
      129.1 +/- 4.3 s (July 1998) before improving to 126.8 +/- 4.2 s (August 1998) (P
      < 0.005). The swimming velocity at LT (s.100 m(-)1) also declined midseason
      before improving before the CG (P < 0.02) (January 1998: 70.5 +/- 2.1; May 1998:
      72.0 +/- 2.2; July 1998: 72.2 +/- 2.2; and August 1998: 70.8 +/- 2.1). The blood
      lactate concentration at the LT decreased (P < 0.02) from 3.6 +/- 0.2 mM to 3.2
      +/- 0.1 mM and 2.9 +/- 0.2 mM before returning to 3.4 +/- 0.2 mM for January,
      May, July, and August, respectively. The lactate tolerance rating (LT(5--10)),
      defined as the differential velocity between lactate concentrations of 5.0 and
      10.0 mM, declined midway through the season (P < 0.015): 6.6 +/- 0.5 s.100 m(-1),
      7.7 +/- 0.5 s.100 m(-1), 8.5 +/- 0.5 s.100 m(-1), and 6.9 +/- 0.4 s.100 m(-1),
      for January, May, July, and August, respectively. Despite these improvements in
      indicators of fitness, there was no significant improvement in competition
      performance across the season. CONCLUSIONS: Maximal effort 200-m time, lactate
      tolerance rating, and swimming velocity at LT (s.100 m(-1)) all improved in world
      ranked swimmers with training, but these changes were not directly associated
      with competition performance.

PMID- 11224821
TI  - Optimal time of arrival for performance at moderate altitude (1700 m).
AB  - PURPOSE: The time course of physiological exercise responses after acute ascent
      to moderate altitude was investigated. METHODS: Fifteen young male subjects (16.5
      +/- 0.8 yr) completed one familiarization and then two further sea level sessions
      to determine sea level values (SL). Subjects were then tested 6 h (ALT1), 18 h
      (ALT2), and 47 h (ALT3) after arrival at 1700 m. Subjects completed a 5-min
      submaximal cycle test, shuttle run test, and 45-s repeated push-up test.
      Hemoglobin (Hb) and hematocrit (Hct) were measured. RESULTS: Cycle test heart
      rate (HR) was higher at ALT1 than SL (182 +/- 15 vs 177 +/- 16 b.min(-1), P <
      0.01) but had returned to 177 +/- 13 and 176 +/- 12 b.min(-1) at ALT2 and ALT3,
      respectively. At ALT1, only five subjects completed the full 5 min. Postexercise
      plasma lactate was not different. Shuttle test HR was higher at ALT1 than SL (191
      +/- 8 vs 185 +/- 14 b.min(-1), P = 0.01) but had returned to 185 +/- 10 and 183
      +/- 16 b.min(-1) at ALT2 and ALT3. Shuttle run time (SRT) was 37% shorter at ALT1
      than SL (251 +/- 134 vs 401 +/- 115 s, P < 0.001) and remained impaired at ALT2
      and ALT3 (330 +/- 124 and 344 +/- 115 s, both P < 0.001 vs SL). There was a
      significant relationship between magnitude of increased HR and reduction in SRT
      between SL and ALT1 (r = 0.52, P < 0.05). Push-up HR, Hb, and Hct were not
      affected by altitude. CONCLUSIONS: These findings indicate that detrimental
      effects of acute ascent to 1700 m on exercise performance are greater after 6 h
      than after 18 or 47 h. Performance was not entirely restored to SL values even
      after 47 h, despite restoration of easily measured physiological parameters. The
      results suggest travel to moderate altitude should occur as early as is practical
      before competition.

PMID- 11224822
TI  - Metabolic demands of intense aerobic interval training in competitive cyclists.
AB  - PURPOSE: To investigate the metabolic demands of a single session of intense
      aerobic interval training in highly trained competitive endurance cyclists.
      METHODS: Seven cyclists (peak O2 uptake [VO2 peak] 5.14 +/- 0.23 L x min(-1),
      mean +/-SD) performed 8 x 5 min work bouts at 86 +/- 2% of VO2 peak with 60-s
      recovery. Muscle biopsies were taken from the vastus lateralis immediately before
      and after the training session, whereas pulmonary gas exchange and venous blood
      were sampled at regular intervals throughout exercise. RESULTS: Muscle glycogen
      concentration decreased from 501 +/- 91 to 243 +/- 51 mmol x kg (-1) dry mass (P
      < 0.01). High rates of total carbohydrate oxidation were maintained throughout
      exercise (340 micromol.kg(-1).min(-1)), whereas fat oxidation increased from 16
      +/- 8 during the first to 25 +/- 13 micromol x kg(-1) x min(-1) during the
      seventh work bout (P < 0.05). Blood lactate concentration remained between 5 and
      6 mM throughout exercise, whereas muscle lactate increased from 6 +/- 1 at rest
      to 32 +/- 12 mmol x kg(-1) d.m. immediately after the training session (P <
      0.01). Although muscle pH decreased from 7.09 +/- 0.06 at rest to 7.01 +/- 0.03
      at the end of the session (P < 0.01), blood pH was similar after the first and
      seventh work bouts (7.34). Arterial oxygen saturation (% S(P)O2) fell to 95.6 +/-
      1% during the first work bout and remained at 94% throughout exercise: the 60-s
      rest intervals were adequate to restore % S(P)O2) to 97%. CONCLUSION: Highly
      trained cyclists are able to sustain high steady state aerobic power outputs that
      are associated with high rates of glycogenolysis and total energy expenditure
      similar to those experienced during a 60-min competitive ride.

PMID- 11224823
TI  - Effects of shoe sole construction on skeletal motion during running.
AB  - PURPOSE: The purpose of this study was to quantify effects of shoe sole
      modification on skeletal kinematics of the calcaneus and tibia during the stance
      phase of running. METHODS: Intracortical bone pins with reflective marker triads
      were inserted under standard local anesthetic into the calcaneus and tibia of
      five healthy male subjects. The three-dimensional tibiocalcaneal rotations were
      determined using a joint coordinate system approach. Three shoe sole
      modifications were tested with different sole geometry: a lateral heel flare of
      25 degrees (flared), no flare 0 degrees (straight), and a rounded sole. RESULTS:
      The results showed that these shoe sole modifications did not change
      tibiocalcaneal rotations substantially. The shoe sole effects at the bone level
      were small and unsystematic (mean effects being less than 1 degrees ) compared
      with the differences between the subjects (up to 7 degrees ). Shoe eversion
      measured simultaneously with shoe markers showed no systematic shoe sole effects.
      A comparison of shoe and bone results showed the total shoe eversion and maximum
      shoe eversion velocity to be approximately twice as large as the respective
      measurements based on bone markers (correlations being r = 0.79 for maximum
      eversion velocity; r = 0.88 for total eversion), indicating that there may be a
      relationship or coupling effect between the shoes and the bone. CONCLUSIONS: It
      is concluded that the tibiocalcaneal kinematics of running may be individually
      unique and that shoe sole modifications may not be able to change them
      substantially.

PMID- 11224824
TI  - Use of orthoses lowers the O(2) cost of walking in children with spastic cerebral
      palsy.
AB  - PURPOSE: The aim of this study was to assess the effects of hinged ankle foot
      orthoses (AFO) on the metabolic and cardiopulmonary cost of walking and gross
      motor skills of children with cerebral palsy (CP). METHODS: Ten habitual users of
      hinged AFO with spastic diplegic CP (9.01 yr +/- 2.10) participated in the study.
      Expired gas and heart rate (HR) were measured during sitting and with AFO on and
      off during steady state treadmill walking at three speeds: 3 km.h(-1),
      comfortable walking speed (CWS), and 90% of their fastest walking speed (FWS).
      Comfortable and fastest ground walking speed and Gross Motor Function Measure
      scores were also assessed with AFO on and off and analyzed with ANOVA. Because
      not all children could walk at all speeds on the treadmill, an ANOVA was
      performed on data for children who walked at 3 km.h(-1) and CWS (N = 8 for HR; N
      = 9 for pulmonary ventilation and metabolic variables) and a t-test on data at
      90% of FWS (N = 9 for HR; N = 8 for pulmonary ventilation and metabolic
      variables). RESULTS: When children wore their AFO net oxygen uptake (L.min(-1),
      absolute--sitting values) was significantly (P < 0.05) reduced by 8.9% at 3 km.h(
      1) and by 5.9% at 90% of FWS. Net pulmonary ventilation (L.min(-1)) was
      significantly (P < 0.05) lower with AFO on by 10.3% but only at 3 km.h(-1). AFO
      did not affect net HR (beats.min(-1)) nor the respiratory exchange ratio at any
      speed, nor any physiologic variable at CWS, nor gross motor skills. CONCLUSIONS:
      Use of hinged AFO reduces the oxygen and ventilatory cost of walking in children
      with spastic diplegic CP.

PMID- 11224825
TI  - Leg power and hopping stiffness: relationship with sprint running performance.
AB  - PURPOSE: Although sprint performance undoubtedly involves muscle power, the
      stiffness of the leg also determines sprint performance while running at maximal
      velocity. Results that include both of these characteristics have not been
      directly obtained in previous studies on human runners. We have therefore studied
      the link between leg power, leg stiffness, and sprint performance. METHODS: The
      acceleration and maximal running velocity developed by 11 subjects (age 16 +/- 1)
      during a 40-m sprint were measured by radar. Their leg muscle volumes were
      estimated anthropometrically. Leg power was measured by an ergometric treadmill
      test and by a hopping test. Each subject executed a maximal sprint acceleration
      on the treadmill equipped with force and speed transducers, from which forward
      power was calculated. A hopping jump test was executed at 2 Hz on a force
      platform. Leg stiffness was calculated using the flight and contact times of the
      hopping test. RESULTS: The treadmill forward leg power was correlated with both
      the initial acceleration (r = 0.80, P < 0.01) and the maximal running velocity (r
      = 0.73, P < 0.05) during track sprinting. The leg stiffness calculated from
      hopping was significantly correlated with the maximal velocity but not with
      acceleration. CONCLUSION: Although muscle power is needed for acceleration and
      maintaining a maximal velocity in sprint performance, high leg stiffness may be
      needed for high running speed. The ability to produce a stiff rebound during the
      maximal running velocity could be explored by measuring the stiffness of a
      rebound during a vertical jump.

PMID- 11224826
TI  - Assessment of the reliability of high-intensity quadriceps femoris muscle
      fatigue.
AB  - OBJECTIVE: The purpose of this study was to evaluate test-retest reliability of
      two different measures of isokinetic quadriceps muscle fatigue. METHODS: Subjects
      for this study included 16 healthy, college age volunteers. Each subject
      performed 30 maximal, concentric repetitions on the Biodex System II Isokinetic
      Dynamometer at a preset angular velocity of 180 degrees.s(-1) for both the
      dominant and nondominant legs. Quadriceps work was evaluated between an angular
      range of 10 degrees and 60 degrees of flexion for each repetition. Quadriceps
      muscle fatigue was calculated through a fatigue index (work performed last 5
      repetitions/work performed first five repetitions x 100) and the linear slope
      (beta) across the 30 repetitions. The subjects participated in two test sessions
      separated by one to two weeks. Intraclass correlation coefficients (ICC) and
      standard errors of measurements (SEM) were calculated for each fatigue measure on
      both legs. RESULTS: The findings demonstrated moderate to high ICCs for the
      nondominant leg (ICC = 0.78--0.92) and high ICCs for the slope and y-intercept
      for the dominant leg (ICC = 0.82 and 0.89, respectively). The fatigue index for
      the dominant leg was found to be low (ICC = 0.26). CONCLUSIONS: The findings of
      this study suggest that the quantification of muscle fatigue during high
      intensity, short-term exercise is more reliably described by the slope, which is
      related to the magnitude of force output.

PMID- 11224827
TI  - Indices of lactate threshold and their relationship with 10-km running velocity.
AB  - PURPOSE: The object of this study was to determine the relationship of three
      measures of running velocity at lactate threshold (LT) with 10-km running
      velocity. The methods used to determine LT velocity (m.s(-1)) during submaximal
      treadmill running were: 1) LT(1), the velocity preceding two consecutive
      increases in blood lactate > or = 1 mmol.L(-1); 2) LT(D), the velocity associated
      with the maximum perpendicular distance between the nonlinear regression line and
      the straight line formed by the two end data points of the blood lactate profile;
      and 3) LT(4), the velocity corresponding to a blood lactate concentration of 4
      mmol.L(-1). METHODS: Thirty competitive and recreational runners (11 female and
      19 male) undertook two 10-km time trials (7 d apart), three treadmill
      familiarization sessions over the following 21 d, and then completed an
      incremental submaximal treadmill run. From blood lactate samples taken during the
      submaximal run, mean LT velocity (+/- SD) at LT(1) (3.76 +/- 0.57), LT(D) (3.79
      +/- 0.58), and LT(4) (4.11 +/- 0.64) was determined. Pearson product moment
      correlation analysis revealed a strong relationship between all mean LT speeds
      and mean 10-km running velocity (3.77 +/- 0.57), with the strongest relationship
      observed for LT(D) (r = 0.86, P < 0.001). Correlations by gender between LT(D)
      and 10-km velocity were r = 0.84 (female) and r = 0.78 (male). Male subjects had
      significantly higher LT velocities than female subjects using all methods (P <
      0.001), and velocity at LT(4) was significantly faster than 10-km velocity and
      velocity at LT(1) and LT(D) (P < 0.001). CONCLUSION: Of the methods measured,
      LT(D) appears to be the most sensitive and valid measure of LT velocity and may
      be of benefit in monitoring the training program of 10-km distance runners.

PMID- 11224828
TI  - Oral oseltamivir treatment of influenza in children.
AB  - BACKGROUND: Oral oseltamivir administration is effective treatment for influenza
      in adults. This study was conducted to determine the efficacy, safety and
      tolerability of oseltamivir in children with influenza. METHODS: In this
      randomized, double blind, placebo-controlled study, children 1 through 12 years
      with fever [> or =100 degrees F (> or =38 degrees C)] and a history of cough or
      coryza <48 h duration received oseltamivir 2 mg/kg/dose or placebo twice daily
      for 5 days. The primary efficacy endpoint was the time to resolution of illness
      including mild/absent cough and coryza mild/absent, return to normal activity and
      euthermia. RESULTS: Of 695 enrolled children 452 (65%) had influenza (placebo, n
      = 235; oseltamivir, n = 217). Among infected children the median duration of
      illness was reduced by 36 h (26%) in oseltamivir compared with placebo recipients
      (101 h; 95% confidence interval, 89 to 118 vs. 137 h; 95% confidence interval,
      125 to 150; P < 0.0001). Oseltamivir treatment also reduced cough, coryza and
      duration of fever. New diagnoses of otitis media were reduced by 44% (12% vs.
      21%). The incidence of physician-prescribed antibiotics was significantly lower
      in influenza-infected oseltamivir (68 of 217, 31%) than placebo (97 of 235, 41%;
      P = 0.03) recipients. Oseltamivir therapy was generally well-tolerated, although
      associated with an excess frequency of emesis (5.8%). Discontinuation because of
      adverse events was low in both groups (1.8% with oseltamivir vs. 1.1% with
      placebo). Oseltamivir treatment did not affect the influenza-specific antibody
      response. CONCLUSIONS: Oral oseltamivir administration is an efficacious and well
      tolerated therapy for influenza in children when given within 48 h of onset of
      illness.

PMID- 11224829
TI  - Increase of Enterobacter in neonatal sepsis: a twenty-two-year study.
AB  - BACKGROUND: Data on the incidence of Enterobacter infections in neonates over
      prolonged periods of time are scant. We determined the epidemiology of
      Enterobacter sepsis and/or meningitis and the trends of infection in a neonatal
      unit. METHODS: Retrospective review of sepsis and/or meningitis in inborn
      neonates admitted to Son Dureta University Hospital during a 22-year period.
      Molecular study by ribotyping of the Enterobacter strains isolated from 1995 to
      1997. RESULTS: There were 513 cases of culture-proved sepsis and/or meningitis in
      neonates. In late onset infections Klebsiella pneumoniae and Staphylococcus
      epidermidis were the most frequent isolates in the period 1977 through 1991.
      Enterobacter was the most common isolate in the period 1992 through 1998. During
      this latter period Candida infections also increased, and the resistance rate of
      Enterobacter to cefotaxime was higher (59.2%). Decrease in early onset infections
      and increase in late onsets (4.6/1,000 live births) were observed in the second
      period. From 1977 to 1998, 45 episodes of sepsis and/or meningitis by
      Enterobacter species were identified in 44 patients (8.7% of all neonatal
      bacteremias). Three patients with Enterobacter bacteremia died (6.6%, 0.03/1,000
      live births). During 1995 through 1997 5 different clones causing sepsis were
      identified and 3 were predominant. In 1997 there was an outbreak of Enterobacter
      disease. After cleaning, cohort nursing and hygiene reinforcement, Enterobacter
      was not isolated in the next 2 years. No change in the antibiotic policy was
      made. CONCLUSIONS: We observed a resurgence of Enterobacter infections in our
      neonatal intensive care unit. The sudden disappearance of this microorganism
      after reinforcement of hygienic measures, without withdrawing cefotaxime,
      confirms the importance of patient-to-patient transmission of this nosocomial
      infection. Further studies are needed to establish the role of antibiotics in the
      emergence of microorganisms in neonatal intensive care units.

PMID- 11224831
TI  - Comparison of the urine-based ligase chain reaction test to culture for detection
      of Chlamydia trachomatis and Neisseria gonorrhoeae in pediatric sexual abuse
      victims.
AB  - BACKGROUND: The urine-based ligase chain reaction (LCR) assay for Chlamydia
      trachomatis and Neisseria gonorrhoeae is an attractive alternative to culture
      because of the relative ease with which specimens may be collected, transported
      and processed. In addition LCR offers superior sensitivity while maintaining high
      specificity when compared with culture in various studies of adolescents and
      adults. A study comparing LCR to culture has not been published concerning
      children. METHODS: We conducted a prospective, comparison trial of the urine
      based LCR test for Chlamydia trachomatis and Neisseria gonorrhoeae as compared
      with culture among children at a specialized referral center for evaluation for
      alleged sexual assault. Of the 1,010 children presenting to the center during the
      study period, 164 met the study requirements for risk of a sexually transmissible
      disease and collection of both culture and urine LCR specimens. RESULTS: Eight
      specimens tested positive by both methods for C. trachomatis. Another 10
      specimens tested positive for C. trachomatis by LCR but were negative by culture.
      No patient with a negative LCR for C. trachomatis had a positive culture. For N.
      gonorrhoeae 2 specimens tested positive by both methods, and 3 specimens tested
      positive by LCR but negative by culture. No patient with a negative LCR for N.
      gonorrhoeae had a positive culture. CONCLUSIONS: The low prevalence of disease in
      the study population precluded statistical analysis. LCR may prove to be as
      specific and more sensitive than culture for the detection of C. trachomatis and
      N. gonorrhoeae in children. Further studies are needed.

PMID- 11224830
TI  - National differences in incidence of acute mastoiditis: relationship to
      prescribing patterns of antibiotics for acute otitis media?
AB  - BACKGROUND: Operating on the principle that most acute otitis media (AOM)
      episodes resolve without antibiotics, doctors in the Netherlands usually manage
      AOM in children with initial observation. Prescription of antibiotics is limited
      to children with a complicated course of AOM and those categorized as high risk.
      Consequently only 31% of patients with AOM receives antibiotics, compared with
      >90% in most other countries. OBJECTIVE: To substantiate the suggestion that this
      restrictive use of antibiotics leads to a higher incidence of acute mastoiditis.
      METHODS: A comparative study across several European countries, Canada, Australia
      and the United States was performed in the period 1991 to 1998. The incidence
      rate of acute mastoiditis was defined as the total number of patients age 14
      years and younger discharged from all hospitals with the primary diagnosis of
      acute mastoiditis, during a specified period (usually 5 years), divided by the
      number of person years (py) in that same age range and period. The latter was
      calculated by totaling the midyear population estimate of children age 14 years
      and younger of each year. The 95% confidence intervals and incidence rate ratios
      were calculated to compare the observed rates. RESULTS: The incidence rate of
      acute mastoiditis in the Netherlands, with a low antibiotic prescription rate for
      AOM, was 3.8/100,000 py; in Norway and Denmark, with high prescription rates, the
      incidence rate was comparable at 3.5/100,000 py and 4.2/100,000 py, respectively.
      In all other countries with very high prescription rates, incidence rates were
      considerably lower, ranging from 1.2 to 2.0/100,000 py. The incidence rate in the
      Netherlands was about twice that in the United States (rate ratio, 0.5).
      CONCLUSION: The incidence rate of acute mastoiditis in the Netherlands is higher
      than in many countries with higher antibiotic prescription rates. Although the
      potential benefits of restricted use of antibiotics (i.e. cost reduction, fewer
      side effects from antibiotics and less antimicrobial resistance) are beyond
      dispute, such strategy may be associated with a somewhat higher incidence of
      acute mastoiditis.

PMID- 11224832
TI  - Epstein-Barr virus burden in adolescents with systemic lupus erythematosus.
AB  - OBJECTIVE: We sought to determine whether patients with systemic lupus
      erythematosus (SLE) and a presumed primary or reactivated Epstein-Barr virus
      (EBV) serologic response had evidence of an active EBV infection. BACKGROUND:
      Patients with SLE often have what appears to be a primary or reactivated EBV
      serologic response. If these patients then present with fever, fatigue,
      adenopathy or leukopenia, it is not clear whether these symptoms are caused by
      worsening SLE or EBV infection. Establishing the correct diagnosis is crucial for
      management. METHODS: We examined the EBV burden in 13 adolescents with SLE and a
      presumed primary or reactivated EBV serologic response. All were taking
      prednisone; 2 each were also on azathioprine or intravenous pulse
      cyclophosphamide. EBV serologies were performed for all, and EBV burdens were
      assessed via immortalization assays and EBV DNA amplification of blood and saliva
      at least once. RESULTS: Seven patients had serologic patterns indicative of a
      primary EBV infection, while six had serologies indicative of a reactivated
      (secondary) EBV infection. Two of the latter were the only ones in whom a small
      amount of biologically active EBV was detected. CONCLUSION: In our series active
      EBV infection was not seen in most patients, despite serologic data that could be
      interpreted as a primary or reactivated infection. Thus the serologic profiles
      were more likely a consequence of immune dysregulation secondary to SLE or its
      therapy rather than rampant infection with EBV.

PMID- 11224833
TI  - Safety and immunogenicity of four doses of Neisseria meningitidis group C vaccine
      conjugated to CRM197 in United States infants.
AB  - BACKGROUND: Following widespread use of conjugate pneumococcal vaccine, Neisseria
      meningitidis likely will become the leading cause of bacterial sepsis and
      meningitis in US children. This report describes the safety and immunogenicity in
      US children of four consecutive doses of a meningococcal group C vaccine
      conjugated to CRM197 via reductive amination (MnCC). METHODS: One hundred six
      healthy 2-month-old infants received MnCC at 2, 4 and 6 months of age in a
      randomized, controlled double blind study; children in the other treatment arm
      were given a 7-valent conjugate pneumococcal vaccine. Parents reenrolled 64 of
      these children at 12 to 15 months to receive a fourth dose of MnCC. Routine
      childhood vaccines, including DTP, were coadministered. Temperatures and symptoms
      were recorded for 3 days after each immunization. Serum enzyme-linked
      immunosorbent assay IgG and bactericidal antibodies were measured prevaccination
      and before and 1 month after Doses 3 and 4. RESULTS: Moderate to severe local
      reactions, defined as erythema or induration > or =2.4 cm or pain that interfered
      with limb movement was reported after 0 to 3.2% of MnCC injections, depending on
      the reaction and dose. Fever occurred in 23 to 37% of children, but the
      contribution of MnCC to the febrile reactions is unknown. Geometric mean
      concentrations of IgG antibody to group C meningococcal polysaccharide were 3.72
      microg/ml after Dose 3 and 8.03 microg/ml after the booster. Geometric mean
      functional serum bactericidal antibody titers after Doses 3 and 4 were 1:463 and
      1:2341, respectively. One hundred percent of children had a serum bactericidal
      antibody titer of > or =1:64 after three doses and > or = 1:128 after the
      booster. CONCLUSIONS: The MnCC vaccine had an acceptable safety profile and
      generated high titers of bactericidal antibody in immunized US infants and
      toddlers. It appears to be an attractive candidate vaccine for the prevention of
      serogroup C meningococcal disease in young children.

PMID- 11224834
TI  - Medical consumption and socioeconomic effects of infection with respiratory
      syncytial virus in The Netherlands.
AB  - OBJECTIVE: To calculate both medical consumption and socioeconomic effects
      related to hospitalization for respiratory syncytial virus (RSV) infection in the
      Netherlands. METHODS: During the winter seasons of 1998 to 2000, parents of all
      patients hospitalized for RSV in three secondary care hospitals were asked to
      fill out questionnaires focusing on the 2 weeks before hospitalization, the
      period in hospital and the 2 weeks after discharge. The questions concerned
      workdays lost, level of education and current profession, extra childcare needed,
      consultation by the family physician and drugs prescribed and costs of
      travelling. RESULTS: Seventy-three children were hospitalized. Median age was 79
      days (range, 9 to 537 days), and median weight was 5,295 g (range, 3130 to 10,600
      g). Three children were born preterm. Parents had 2 (range, 0 to 6) telephone
      contacts with the family doctor; the child was seen 2 (range, 0 to 4) times
      before hospitalization. Parents lost 0.5 workday before hospitalization. Duration
      of hospitalization was 5 days median (range, 1 to 12 days). Parents lost 1.5
      (range, 0 to 9) workdays during hospitalization and drove 118 (range, 6 to 550)
      miles to visit their child. In the period after discharge expenses were
      negligible. Calculation of all parameters into currency resulted in a total
      amount of $2,200 per child hospitalized for RSV. Workdays lost, costs for
      travelling and consultation of family doctors resulted in $295 per child.
      CONCLUSIONS: RSV infections necessitating hospitalization in a secondary care
      hospital have remarkable effects on parental expenses, parental absence from work
      and medical consumption. On top of the hospital-related costs 15% should be added
      for parental expenses and socioeconomic costs.

PMID- 11224836
TI  - Differing manifestations of respiratory syncytial virus-associated severe lower
      respiratory tract infections in human immunodeficiency virus type 1-infected and
      uninfected children.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) causes increased morbidity and
      mortality in immunocompromised children. The outcome of RSV-associated lower
      respiratory tract infections (LRTI) in HIV-infected children, is less well
      described. METHODS: Children from a prospective study evaluating the etiology of

PMID- 11224837
TI  - Does the empiric use of vancomycin in pediatrics increase the risk for Gram
      negative bacteremia?
AB  - BACKGROUND: Gram-negative bacteremia in children, a major cause of morbidity and
      mortality, may in part be induced by intensive treatment procedures and
      nonspecific use of antibiotics. Our primary objective was to study the causal
      relationship between the use of vancomycin and Gram-negative bacteremia, for
      which this antibiotic is not specifically indicated. METHODS: The study was
      conducted in a 105-bed tertiary care children's hospital in the period of 1994 to
      1997. The study pertains to a cohort of children with suspected bacteremia, in
      whom a blood culture was performed during hospital stay. Using the bacteriologic
      laboratory registration system, we selected all pediatric cases with
      bacteriologically proved Gram-negative bacteremia (n = 105) and a random sample
      of 225 pediatric controls with negative blood cultures. Using logistic regression
      analysis we examined associations between Gram-negative bacteremia and the
      following factors: preceding use of antibiotics, antacids, corticosteroids,
      surgery, mechanical ventilation, parenteral nutrition, and invasive
      instrumentation; and the intensity of care assessed with the Therapeutic
      Intensity Scoring System (TISS 28). RESULTS: Gram-negative bacteremia was
      positively associated with the use of aminoglycosides, cephalosporins, surgical
      interventions, central venous catheters, parenteral nutrition, antacids and
      dexamethasone. The strongest association was with the use of vancomycin (odds
      ratio, 8.1; 95% confidence interval, 3.1 to 20.9). In a multiple logistic
      regression model containing all above-mentioned variables, the use of vancomycin
      remained positively and strongly associated with Gram-negative bacteremia (odds
      ratio, 3.88; 95% confidence interval, 1.34 to 11.21). Further adjustments and
      restrictions in the analysis did not materially change these findings concerning
      vancomycin. CONCLUSIONS: Among children suspected of bacteremia there are several
      drugs and clinical procedures influencing the risk for Gram-negative bacteremia.
      Empiric use of vancomycin is strongly and independently associated with Gram
      negative bacteremia. The safety of using vancomycin solely on the basis of
      suspicion of bacteremia in children may not be warranted.

PMID- 11224838
TI  - Homeopathic treatment of acute otitis media in children: a preliminary randomized
      placebo-controlled trial.
AB  - BACKGROUND: The use of antibiotics in the initial treatment of acute otitis media
      is currently being questioned. Homeopathy has been used historically to treat
      this illness, but there have been no methodologically rigorous trials to
      determine whether there is a positive treatment effect. METHODS: A randomized
      double blind placebo control pilot study was conducted in a private pediatric
      practice in Seattle, WA. Seventy-five children ages 18 months to 6 years with
      middle ear effusion and ear pain and/or fever for no more than 36 h were entered
      into the study. Children received either an individualized homeopathic medicine
      or a placebo administered orally three times daily for 5 days, or until symptoms
      subsided, whichever occurred first. Outcome measures included the number of
      treatment failures after 5 days, 2 weeks and 6 weeks. Diary symptom scores during
      the first 3 days and middle ear effusion at 2 and 6 weeks after treatment were
      also evaluated. RESULTS: There were fewer treatment failures in the group
      receiving homeopathy after 5 days, 2 weeks and 6 weeks, with differences of 11.4,
      18.4 and 19.9%, respectively, but these differences were not statistically
      significant. Diary scores showed a significant decrease in symptoms at 24 and 64
      h after treatment in favor of homeopathy (P < 0.05). Sample size calculations
      indicate that 243 children in each of 2 groups would be needed for significant
      results, based on 5-day failure rates. CONCLUSIONS: These results suggest that a
      positive treatment effect of homeopathy when compared with placebo in acute
      otitis media cannot be excluded and that a larger study is justified.

PMID- 11224839
TI  - Economic impact of community- and nosocomially acquired rotavirus gastroenteritis
      in Austria.
AB  - OBJECTIVE: To determine the average costs per child for rotavirus (RV) acute
      gastroenteritis from different perspectives, from the hospital's, third-party
      payer's, pediatrician's and family's perspectives as well as in summary from the
      societal one. MATERIALS AND METHODS: This cost-of-illness study is based on data
      collected alongside a 6-month prospective, laboratory-confirmed epidemiologic
      study that evaluated the disease burden of RV infection in Austrian children < or
      =48 months of age. The study population at risk to contract a community- and
      nosocomially acquired acute gastroenteritis comprised 9,687 children. All of the
      51 children with community-acquired and 33 with nosocomially acquired RV acute
      gastroenteritis were included in this analysis. The annual costs were estimated
      by means of extrapolation. RESULTS: For community-acquired RV acute
      gastroenteritis, the average costs from the hospital's perspective were EURO
      (EUR) 97.8, from the third party payer's perspective 95.6 EUR, followed by 29.9
      EUR and 9.8 EUR from the family's and pediatrician's perspectives, respectively.
      For nosocomially acquired RV acute gastroenteritis the average costs from the
      hospital's perspective were 1,494 EUR and from the third party payer's and
      family's perspectives 831 EUR and 116.8 EUR, respectively. In summary the average
      costs from the societal point of view for community-acquired RV acute
      gastroenteritis were 250 EUR and for nosocomial infections 2,442 EUR. After
      extrapolation the estimated total annual costs were 7.17 EUR million to 0.97 EUR
      million (13.6%) caused by community-acquired RV acute gastroenteritis and 6.2 EUR
      million (86.4%) caused by nosocomial RV acute gastroenteritis. CONCLUSION: This
      cost-of-illness study clearly demonstrates the great impact of RV acute
      gastroenteritis, mainly of nosocomially acquired infection, on medical health
      care costs in Austria. To cut costs efforts in disease prevention should be
      encouraged.

PMID- 11224840
TI  - Congenital cytomegalovirus infection in preterm and full-term newborn infants
      from a population with a high seroprevalence rate.
AB  - BACKGROUND: Cytomegalovirus (CMV) is the most frequent cause of congenital
      infections in humans. Prematurity occurs in as many as 34% of infants with
      symptomatic congenital CMV infection. OBJECTIVE: To determine the clinical
      presentation and frequency of congenital CMV infection among preterm infants and
      full-term infants from a population with a high seroprevalence rate.
      DESIGN/METHODS: A total of 289 preterm infants (median gestational age, 34 weeks;
      median birth weight, 1,757 g) and 163 term infants (median gestational age, 39
      weeks; median birth weight, 3,150 g) sequentially born were included in the
      study. Serum IgG antibodies to CMV were measured in all mothers. One urine sample
      was collected within the first 7 days of age from all newborns. Virus isolation
      in urine samples was performed by tissue culture, and viral DNA was detected by a
      multiplex PCR. CMV infection was diagnosed in infants with virus excretion
      detected by both methods on at least two occasions within the first 3 weeks of
      life. RESULTS: Maternal CMV seropositivity rate was 95.7%. Congenital CMV
      infection was detected in 6 of 289 (2.1%) (95% confidence interval, 0.84 to 4.68)
      preterm infants and in 3 of 163 term infants (1.8%) (95% confidence interval,
      0.48 to 5.74) (P > 0.05). Four of 6 preterm infants with congenital CMV infection
      were symptomatic, but none of the term infants was symptomatic (P = 0.16).
      CONCLUSION: The frequency of congenital CMV infection in preterm newborn infants
      from mothers with a high seropositive rate was similar to that found in term
      infants. No significant difference was found between the proportion of
      symptomatic infants among preterm and term infants. Our finding of symptomatic
      congenital CMV infection underscores the need of further evaluation of correlates
      of congenital symptomatic infection in highly immune populations.

PMID- 11224841
TI  - Treatment of Giardia lamblia infections.

PMID- 11224842
TI  - Infectious causes of persistent diarrhea.

PMID- 11224843
TI  - Chronic mucocutaneous candidiasis.
AB  - Chronic mucocutaneous candidiasis should be viewed as a spectrum of disorders in
      which the patients have persistent and/or recurrent candidiasis of the skin,
      nails and mucous membranes. Some of the conditions have genetic predispositions.
      A common immunologic abnormality is failure of the patient's T lymphocytes to
      produce cytokines that are essential for expression of cell-mediated immunity to
      Candida. Antifungal drugs are effective in clearing the infections, and
      treatments that restore cellular immunity have produced long term remissions.

PMID- 11224844
TI  - Bacterial infections and inflammation in the lungs of cystic fibrosis patients.
AB  - The aim of this review is to describe the role of respiratory epithelial cells in
      processes that contribute to the pathogenesis of lung disease in patients with
      cystic fibrosis.

PMID- 11224845
TI  - Misuse of antimicrobials in children with asthma and bronchiolitis: a review.
AB  - Of 200 children hospitalized because of asthma or bronchiolitis, 100 received
      antibiotics inappropriately.

PMID- 11224846
TI  - Viral etiologies of encephalitis in Thai children.
AB  - A prospective study of childhood encephalitis was performed in Bangkok from 1996
      through 1998. The viral agents identifiable in 26 (65%) of 40 children were
      dengue virus (8), Japanese encephalitis (6), herpes simplex virus (4), human
      herpes virus type 6 (3), mumps (2), enterovirus (1), varicella-zoster virus (VZV)
      (1) and rabies (1).

PMID- 11224847
TI  - Dichloroacetate treatment for severe refractory metabolic acidosis during
      neonatal sepsis.
AB  - We describe a preterm neonate with documented group B Streptococcus sepsis and
      associated metabolic acidosis whose lactic acidemia was refractory to
      conventional sodium bicarbonate therapy but responded well to dichloroacetate
      treatment.

PMID- 11224848
TI  - Stevens-Johnson syndrome and toxic epidermal necrolysis after vaccination:
      reports to the vaccine adverse event reporting system.
AB  - We conducted a telephone survey of reports of Stevens-Johnson syndrome (SJS) and
      toxic epidermal necrolysis (TEN) to the Vaccine Adverse Event Reporting System.
      We identified six cases of SJS or TEN after vaccination without other obvious
      triggers, suggesting that SJS and TEN might very rarely be caused by vaccination.
      Confirmation of this hypothesis will likely require controlled studies.

PMID- 11224849
TI  - Coadministration of mefloquine and chloroqine: use of a pharmacokinetic-based
      approach to reduce toxicity.
AB  - A child with malaria from a chloroquine-resistant area received an accidental
      overdose of chloroquine administered by a parent. Application of pharmacokinetics
      permitted definitive treatment with mefloquine in a safe and effective manner.

PMID- 11224850
TI  - Visceral leishmaniasis in a Brazilian child infected perinatally with human
      immunodeficiency virus.
AB  - This report describes a Brazilian child perinatally infected by HIV who presented
      visceral leishmaniasis. She showed the classic clinical features, and diagnosis
      was made by demonstration of amastigote forms of Leishmania in bone marrow
      aspirate. She responded well to traditional treatment with meglubine.

PMID- 11224851
TI  - Herpes simplex mimicking herpes zoster in a child immunized with varicella
      vaccine.
AB  - A 5-year-old boy had zosteriform vesicular lesions 4 years after immunization
      with varicella vaccine. PCR analyses of DNA extracted from the crusts revealed
      herpes simplex virus type 1 infection. Virologic examinations should be performed
      before the vesicular lesion is attributed to the varicella-zoster virus vaccine
      strain.

PMID- 11224852
TI  - Perinatal herpes simplex infection presenting with pneumonia and pleural
      effusions.
AB  - An unusual case of perinatal herpes infection presenting with pneumonia and
      pleural effusions is described.

PMID- 11224853
TI  - Fever, refusal to walk and eosinophilia in a ten-month-old Samoan boy.

PMID- 11224854
TI  - Trimethoprim-sulfamethoxazole and fulminant ehrlichiosis.

PMID- 11224857
TI  - LYMPHOCUTANEOUS NOCARDIA BRASILIENSIS INFECTION IN CHILDREN.

PMID- 11224855
TI  - Lymphocutaneous Nocardia brasiliensis infection in children.

PMID- 11224858
TI  - The critical stage of pinealectomy surgery after which scoliosis is produced in
      young chickens.
AB  - STUDY DESIGN: Stages of the surgical procedure for pinealectomy in chickens were
      identified. Groups of chickens were selected for each stage. Scoliosis
      development was identified from radiographs. OBJECTIVES: To determine the
      critical stage of surgery for pinealectomy after which scoliosis develops in
      young chickens. SUMMARY OF BACKGROUND DATA: Pinealectomy in young chickens
      consistently produces scoliosis in young chickens that has many characteristics
      similar to those seen in patients with adolescent idiopathic scoliosis. The
      mechanism behind this phenomenon remains unknown. METHODS: Five distinct stages
      in the pinealectomy surgery were identified. Groups of chickens were selected to
      undergo surgery to represent these five stages. Scoliosis was determined from
      weekly radiographs. RESULTS: Cutting the pineal stalk was identified as the
      critical stage in the surgery after which scoliosis developed. The incidence of
      scoliosis did not increase after more extensive surgery in which the pineal bulb
      was removed from the skull. This stage was also correlated with a significant
      reduction of serum melatonin levels. CONCLUSIONS: Cutting the pineal stalk was
      identified as the critical stage of pinealectomy surgery after which scoliosis
      may develop. This stage was also correlated with the significant reduction of
      average serum melatonin levels. These results allow the focus of attention into
      the mechanism behind this phenomenon to center on the consequences of cutting the
      pineal stalk rather than total removal of the pineal gland.

PMID- 11224860
TI  - Ventral discectomy with pmma interbody fusion for cervical disc disease: long
      term results in 249 patients.
AB  - STUDY DESIGN: Retrospective study of patients who underwent ventral discectomy
      and polymethyl-methacrylate (PMMA) interbody fusion for cervical radiculopathy.
      OBJECTIVES: To evaluate the long-term outcome after ventral discectomy and PMMA
      interbody fusion and to compare it with previous data from other surgical
      techniques for the treatment of cervical radiculopathy. SUMMARY OF BACKGROUND
      DATA: Because PMMA interbody fusion after ventral discectomy does not result in
      solid bony fusion in all cases, a good long-term outcome using this surgical
      technique has been questioned. METHODS: Long-term follow-up evaluation after
      surgery was performed in 249 patients (96 women and 153 men) with radicular signs
      only. The mean age was 46.0 +/- 8.7 years (range, 24-74 years), and the
      observation time ranged from 10-15 years (mean, 12.2 +/- 1.2 years). Clinical
      grading after surgery according to Odom's criteria was based on a questionnaire.
      The outcome was related to morphologic findings, lumbar symptoms, physical
      stress, duration of symptoms, age, sex, and cervical level involved. RESULTS:
      Complications related to surgery occurred in 13 (5.2%) patients, but only three
      (1.2%) had persistent problems. Of the 249 patients, 101 (40.6%) were without any
      symptoms (Odom I), 92 (36.9%) had a good outcome (Odom II), and 47 (18.9%) a fair
      outcome (Odom III). Only nine patients (3.6%) reported an unchanged or worse
      status than before surgery (Odom IV). Additional lumbar symptoms, high
      occupational physical stress, and discrepancy of preoperative findings were
      significantly correlated with a worse outcome. Short duration of symptoms and
      soft disc disease were favorable prognostic factors. CONCLUSIONS: PMMA interbody
      fusion after ventral discectomy in cervical disc surgery is a safe and reliable
      method with few complications and an outcome comparable with other ventral
      procedures.

PMID- 11224859
TI  - Long-term results of the anterior floating method for cervical myelopathy caused
      by ossification of the posterior longitudinal ligament.
AB  - STUDY DESIGN: Results of the anterior floating method used to decompress
      ossification of the posterior longitudinal ligament were studied for an average
      postoperative interval of 13 years. OBJECTIVE: To investigate the long-term
      results of the anterior floating method used to manage ossification of the
      posterior longitudinal ligament. SUMMARY OF BACKGROUND DATA: The anterior
      floating method is a technique that differs from the extirpation method used to
      manage ossification of the posterior longitudinal ligament. Reports of the long
      term results from anterior decompression used to manage cervical ossification of
      the posterior longitudinal ligament are rare. METHODS: The anterior floating
      method was used to decompress cervical ossification of the posterior longitudinal
      ligament in 63 patients. These patients were followed for more than 10 years with
      neurologic evaluations using a scoring system proposed by the Japanese Orthopedic
      Association (JOA score). RESULTS: The recovery rate was 66.5% at 10 years and
      59.3% at 13 years, the time of the final survey. Operative outcomes most closely
      reflected the preoperative duration and severity of myelopathy (JOA score) and
      the preoperative cross-sectional area of the spinal cord. There was no
      correlation with the canal narrowing ratio or the thickness of ossification of
      the posterior longitudinal ligament. Delayed deterioration was attributed to an
      original inadequate decompression and progression of ossification of the
      posterior longitudinal ligament outside the original operative field. There was
      no evidence of significant recurrent ossification of the posterior longitudinal
      ligament within the margins of prior decompression. CONCLUSIONS: The anterior
      floating method appears to yield adequate long-term outcomes when used to manage
      ossification of the posterior longitudinal ligament.

PMID- 11224861
TI  - Characteristics of sagittal vertebral alignment in flexion determined by dynamic
      radiographs of the cervical spine.
AB  - STUDY DESIGN: This study was conducted to depict the change patterns of
      intervertebral motion of the cervical spine during flexion, upright, and
      extension positions using dynamic radiographs. Special interest was focused on
      the flexion position. OBJECTIVES: To find reliable criteria for judging the
      normal intervertebral flexibility based on a survey of the normal population.
      METHODS: The lateral dynamic radiographs of 75 normal subjects were analyzed by
      digitization and computer calculation. The characteristics of intervertebral
      positions were investigated using flexion radiographs. RESULTS: From extension to
      flexion, the angles of intervertebral angular displacement changed from lordosis
      with different degrees to nearly 0 degrees, which means the adjacent endplates
      are almost parallel, except at C1-C2; the intervertebral translation changes from
      slightly retrolisthetic to zero displacement. Using C2-C3 as a baseline to
      calculate the intervertebral differences of angular displacement and translation
      in flexion radiographs, nearly all the intervertebral differences of angular
      displacement were less than 7 degrees, and those of translation were less than
      0.06 mm. CONCLUSIONS: Qualitative changes from extension to flexion and
      quantitative values of intervertebral differences in flexion radiographs help
      define the normal flexibility of the cervical spine more accurately.

PMID- 11224862
TI  - Multidisciplinary biopsychosocial rehabilitation for subacute low back pain in
      working-age adults: a systematic review within the framework of the Cochrane
      Collaboration Back Review Group.
AB  - STUDY DESIGN: A systematic review of randomized controlled trials was performed.
      OBJECTIVE: To evaluate the effectiveness of multidisciplinary biopsychosocial
      rehabilitation for subacute low back pain among working-age adults. SUMMARY OF
      BACKGROUND DATA: Multidisciplinary biopsychosocial rehabilitation programs are
      widely applied for patients with chronic low back pain. The multidisciplinary
      biopsychosocial approach for prolonged low back pain could be considered to
      prevent chronicity. Work site visits and a close relationship with occupational
      health care might produce results in terms of patients working ability. METHODS:
      Reviewed randomized controlled trials as well as controlled trials were
      identified from electronic bibliographic databases, reference checking, and
      consultation with experts in the rehabilitation field. Four blinded reviewers
      selected the trials. Two rehabilitation specialists evaluated the clinical
      relevance. Two other blinded reviewers extracted the data and assessed the main
      results along with the methodologic quality of the studies. A qualitative
      analysis was performed to evaluate the level evidence. RESULTS: Of 1808
      references, only 2 relevant studies were included. Both were considered to be
      methodologically low-quality randomized controlled trials. The clinical relevance
      of the studies was sufficient. The level of scientific evidence was moderate,
      showing that multidisciplinary rehabilitation involving work site visit or more
      comprehensive occupational health care intervention helps patients return to work
      faster, makes sick leaves less, and alleviates subjective disability.
      CONCLUSIONS: There is moderate evidence showing that multidisciplinary
      rehabilitation for subacute low back pain is effective, and that work site visit
      increases the effectiveness, but because the analyzed studies had some
      methodologic shortcomings, an obvious need still exists for high-quality trials
      in this field.

PMID- 11224863
TI  - Behavioral treatment for chronic low back pain: a systematic review within the
      framework of the Cochrane Back Review Group.
AB  - STUDY DESIGN: A systematic review of randomized controlled trials. SUMMARY OF
      BACKGROUND DATA: The treatment of chronic low back pain is not primarily focused
      on removing an underlying organic disease but at the reduction of disability
      through the modification of environmental contingencies and cognitive processes.
      Behavioral interventions are commonly used in the treatment of chronic
      (disabling) low back pain. OBJECTIVES: To determine whether behavioral therapy is
      more effective than reference treatments for chronic nonspecific low back pain
      and which type of behavioral treatment is most effective. METHODS: The authors
      searched the Medline and PsychLit databases and the Cochrane Controlled Trials
      Register up to April 1999, and Embase up to September 1999. Also screened were
      references of identified randomized trials and relevant systematic reviews.
      Methodologic quality assessment and data extraction were performed independently
      by two reviewers. The magnitude of effect was assessed by computing a pooled
      effect size for each domain (i.e., behavioral outcomes, overall improvement, back
      pain-specific and generic functional status, return to work, and pain intensity)
      using the random effects model. RESULTS: Only six (25%) studies were high
      quality. There is strong evidence (level 1) that behavioral treatment has a
      moderate positive effect on pain intensity (pooled effect size 0.62; 95%
      confidence interval [CI] 0.25, 0.98), and small positive effects on generic
      functional status (pooled effect size 0.35; 95% CI: -0.04, 0.74) and behavioral
      outcomes (pooled effect size 0.40; 95% CI: 0.10, 0.70) of patients with chronic
      low back pain when compared with waiting-list controls or no treatment. There is
      moderate evidence (level 2) that a addition of behavioral component to a usual
      treatment program for chronic low backpain has no positive short-term effect on
      generic functional status (pooled effect size 0.31; 95% CI: -0.01, 0.64), pain
      intensity (pooled effect size 0.03; 95% CI:-0.30, 0.36), and behavioral outcomes
      (pooled effect size 0.19; 95% CI: -0.08, 0.45). CONCLUSIONS: Behavioral treatment
      seems to be an effective treatment for patients with chronic low back pain,but it
      is still unknown what type of patients benefit most from what type of behavioral
      treatment.

PMID- 11224864
TI  - Global spinal motion in subjects with lumbar spondylolysis and spondylolisthesis:
      does the grade or type of slip affect global spinal motion?
AB  - STUDY DESIGN: This was a prospective pilot study to investigate the global motion
      characteristics of the spondylolysis and spondylolisthesis populations.
      OBJECTIVES: The aim of this study is to determine the influence of a
      spondylolisthesis or a spondylolysis on global spinal motion and to establish
      whether this is dependent on the cause of the slip or the degree/grade of the
      slip. SUMMARY OF BACKGROUND DATA: The condition of spondylolisthesis has been
      extensively discussed in the literature with respect to its etiology and
      management. However, the mechanics and movement of the spine in relation to
      pathology and the effect of this condition on function have received scant
      attention. METHODS: The motion of the lumbar spine was investigated in 31
      patients (19 men, 12 women, mean age 47.7 +/- 17.8 years) who were diagnosed as
      having either a lumbar spondylolysis or a spondylolisthesis. These patients were
      compared with a preexisting database of 203 normal subjects (100 men, 103 women,
      mean age 39.8 +/- 13.4 years). Patients were graded according to the type of
      spondylolisthesis or spondylolysis they had, and the extent of slip was rated
      using Meyerding's classification (1932) and measured directly using methods of
      Boxall et al (1979) and Wiltse et al (1983). RESULTS: Direct measurements of the
      extent of slip using Boxall et al (1979) and Wiltse et al (1983) methods were
      found to have no significant correlation with the resultant range of motion (ROM)
      or the speed of movement. This study suggests that motion parameters are
      influenced by the grade of slip in patients with spondylolisthesis, and the type
      of spondylolisthesis i.e., whether isthmic or degenerative. In the A-P flexion
      extension plane, the results indicate that subjects with a defect only, i.e., a
      spondylolysis, and thus no slip present with a spinal hypermobility (P < 0.01).
      Subjects with an isthmic slip tend to be either slightly hypermobile or within
      the anticipated range of motion, whereas those subjects with a degenerative slip
      tend to be hypomobile (P < 0.05). Movements into lateral flexion were restricted
      in both the isthmic and degenerative spondylolisthesis patients, whereas rotation
      was only influenced by the level at which the defect occurred. In terms of degree
      of displacement, in higher grades of displacement, there was a trend towards
      hypermobility. CONCLUSIONS: The findings of this study suggest that the grade and
      type of spondylolisthesis do influence global motion parameters. This information
      may be useful in the clinical assessment of this patient group.

PMID- 11224865
TI  - Randomized controlled trial of percutaneous intradiscal radiofrequency
      thermocoagulation for chronic discogenic back pain: lack of effect from a 90
      second 70 C lesion.
AB  - STUDY DESIGN: A prospective double-blind randomized trial in 28 patients.
      OBJECTIVES: To assess the clinical effect of percutaneous intradiscal
      radiofrequency thermocoagulation for reducing pain, functional disability, and
      physical impairment in patients with chronic discogenic low back pain. SUMMARY OF
      BACKGROUND DATA: Chronic discogenic low back pain is a challenging problem in
      western countries. A treatment option is radiofrequency heating of the affected
      disc. Its clinical efficacy has never been formally tested in a controlled trial.
      METHODS: Twenty-eight patients with a history of at least 1 year of chronic low
      back pain were selected on the basis of a diagnostic anesthetization of the lower
      intervertebral discs. Only patients with one putative painful level were selected
      and randomly assigned to one of two treatment groups. Each patient in the
      radiofrequency treatment group (n = 13) received a 90-second 70 C lesion of the
      intervertebral disc. Patients in the control group (n = 15) underwent the same
      procedure, but without use of radiofrequency current. Both the treating physician
      and the patients were blinded to the group assignment. Before treatment, physical
      impairment, rating of pain, the degree of disability, and quality of life were
      assessed by a blinded investigator. RESULTS: Eight weeks after treatment, there
      was one success in the radiofrequency group (n = 13) and two in the control group
      (n = 15). The adjusted and unadjusted odds ratio was 0.5 and 1.1, respectively
      (not significant). Also, visual analog scores for pain, global perceived effect,
      and the Oswestry disability scale showed no differences between the two groups.
      CONCLUSIONS: Percutaneous intradiscal radiofrequency thermocoagulation (90
      seconds, 70 C) is not effective in reducing chronic discogenic low back pain.

PMID- 11224866
TI  - Cauda equina syndrome as a postoperative complication in five patients operated
      for lumbar disc herniation.
AB  - STUDY DESIGN: A retrospective analysis of records and radiographs in five
      patients who developed acute cauda equina syndrome after surgery for lumbar disc
      herniation. OBJECTIVES: To postulate as a possible pathophysiologic mechanism the
      venous congestion caused by preexisting spinal stenosis and to present a
      management plan: extended decompression within 48 hours. SUMMARY OF BACKGROUND
      DATA: Cauda equina syndrome is reported as a sequela in 0.2%-1% of the surgeries
      for lumbar disc herniation. There is, however, no consensus on the possible
      pathophysiologic mechanism to the complication or to its management. METHODS:
      Preoperative investigations consisted of magnetic resonance imaging, or
      myelography and computed tomography. There was a good correlation between
      clinical appearance and radiographic findings in all patients. When the
      complication became apparent in four of the patients, they were investigated with
      magnetic resonance imaging and reoperated on within 48 hours with wide
      decompressions. RESULTS: The index operation was reported uneventful in all
      patients. Postoperative magnetic resonance imaging did not show the cause of the
      cauda equina syndrome, nor could this be established at the reoperation. Before
      surgery, all five patients had preexisting narrowing of the spinal canal. In no
      case was the lumbosacral disc the index level. Two patients recovered fully,
      whereas the other three experienced varying degrees of residual symptoms. There
      was no correlation between the end result and the delay until secondary
      decompression. CONCLUSION: Relative spinal stenosis may contribute to the
      development of cauda equina syndrome after surgery for lumbar disc herniation. A
      venous congestion can be triggered by postoperative edema, leading to nerve root
      ischemia. The treatment of choice seems to be extended decompression within 48
      hours.

PMID- 11224867
TI  - Surgical strategy for spinal metastases.
AB  - STUDY DESIGN: A new surgical strategy for treatment of patients with spinal
      metastases was designed, and 61 patients were treated based on this strategy.
      OBJECTIVES: To propose a new surgical strategy for the treatment of patients with
      spinal metastases. SUMMARY OF BACKGROUND DATA: A preoperative score composed of
      six parameters has been proposed by Tokuhashi et al for the prognostic assessment
      of patients with metastases to the spine. Their scoring system was designed for
      deciding between excisional or palliative procedures. Recently, aggressive
      surgery, such as total en bloc spondylectomy for spinal metastases, has been
      advocated for selected patients. Surgical strategies should include various
      treatments ranging from wide or marginal excision to palliative treatment with
      hospice care. METHODS: Sixty-seven patients with spinal metastases who had been
      treated from 1987-1991 were reviewed, and prognostic factors were evaluated
      retrospectively (phase 1). A new scoring system for spinal metastases that was
      designed based on these data consists of three prognostic factors: 1) grade of
      malignancy (slow growth, 1 point; moderate growth, 2 points; rapid growth, 4
      points), 2) visceral metastases (no metastasis, 0 points; treatable, 2 points:
      untreatable, 4 points), and 3) bone metastases (solitary or isolated, 1 point;
      multiple, 2 points). These three factors were added together to give a prognostic
      score between 2-10. The treatment goal for each patient was set according to this
      prognostic score. The strategy for each patient was decided along with the
      treatment goal: a prognostic score of 2-3 points suggested a wide or marginal
      excision for long-term local control; 4-5 points indicated marginal or
      intralesional excision for middle-term local control; 6-7 points justified
      palliative surgery for short-term palliation; and 8-10 points indicated
      nonoperative supportive care. Sixty-one patients were treated prospectively
      according to this surgical strategy between 1993-1996 (phase 2). The extent of
      the spinal metastases was stratified using the surgical classification of spinal
      tumors, and technically appropriate and feasible surgery was performed, such as
      en bloc spondylectomy, piecemeal thorough excision, curettage, or palliative
      surgery. RESULTS: The mean survival time of the 28 patients treated with wide or
      marginal excision was 38.2 months (26 had successful local control). The mean
      survival time of the 13 patients treated with intralesional excision was 21.5
      months (nine had successful local control). The mean survival time of the 11
      patients treated with palliative surgery and stabilization was 10.1 months (eight
      had successful local control). The mean survival time of the patients with
      terminal care was 5.3 months. CONCLUSIONS: A new surgical strategy for spinal
      metastases based on the prognostic scoring system is proposed. This strategy
      provides appropriate guidelines for treatment in all patients with spinal
      metastases.

PMID- 11224868
TI  - Cauda equina syndrome secondary to idiopathic spinal epidural lipomatosis.
AB  - STUDY DESIGN: Three cases of idiopathic epidural lipomatosis are reported.
      OBJECTIVES: Description of the relationship between spinal pathologic overgrowth
      of fat tissue and neurologic symptoms. SUMMARY OF BACKGROUND DATA: Idiopathic
      epidural lipomatosis is a very rare condition; it is usually secondary to chronic
      steroid therapy or endocrinopathic diseases. METHODS: Three men with a mean age
      of 58.5 years, who experienced intermittent claudication, bilateral radicular
      pain in both legs, and urinary dysfunction with hypoesthesia in the perineal
      region, were evaluated by plain radiography and magnetic resonance imaging, the
      results of which demonstrated a pathologic overgrowth of fat tissue in the spinal
      canal with a marked impingement of the dural sac. Obesity, endocrinopathic
      diseases, and chronic steroid therapy were excluded for all patients. Surgical
      treatment was performed by wide multilevel laminectomies, fat debulking, and
      instrumented posterolateral fusion. RESULTS: After surgery there was a gradual
      improvement in symptoms and signs so that 2 years later the patients returned to
      daily activities and were neurologically normal. CONCLUSIONS: Spinal epidural
      lipomatosis can be a cause of back pain but rarely radicular impingement.
      Magnetic resonance imaging is the procedure of choice. The treatment must be
      performed early by wide surgical decompression.

PMID- 11224869
TI  - Intraneural monophasic synovial sarcoma: a case report.
AB  - STUDY DESIGN: A case report. OBJECTIVES: To illustrate a rare case of synovial
      sarcoma arising within a peripheral nerve. SUMMARY OF BACKGROUND DATA: A synovial
      sarcoma arising within a peripheral nerve is very unusual. Only five cases of
      primary synovial sarcoma within a peripheral nerve have been reported. This is
      the first case with involvement of the nerve root. The authors diagnosed the
      tumor arising within the S1 nerve root as synovial sarcoma using cytogenetic
      analysis that detected the chimeric SYT/SSX gene. METHODS: In addition to the
      immunohistochemical study, a reverse transcription-polymerase chain reaction (RT
      PCR) assay was conducted for the SYT-SS10 fusion gene using archival formalin
      fixed paraffin-embedded tumor specimens. RESULTS: Computed tomography scan,
      magnetic resonance imaging performed before surgery, and the intraoperative
      findings showed that the tumor was embedded within the S1 nerve root. Although
      the histologic findings were suggestive of a malignant peripheral nerve sheath
      tumor, the results of the cytologic study confirmed its diagnosis of synovial
      sarcoma. CONCLUSION: Primary intraneural synovial sarcoma, although rare, must be
      distinguished from malignant peripheral nerve sheath tumor. The molecular assay
      of the detection of the SYT/SSX fusion gene is useful to make a definite
      diagnosis of monophasic synovial sarcoma.

PMID- 11224870
TI  - Masking of vertebral artery dissection by severe trauma to the cervical spine.
AB  - STUDY DESIGN: A prospective case study was performed. OBJECTIVES: To illustrate
      the association of cervical trauma with vertebral artery dissection, and to
      propose a diagnostic and therapeutic algorithm for suspected traumatic vertebral
      artery dissection. SUMMARY OF BACKGROUND DATA: Vertebral artery dissection is a
      recognized but underdiagnosed complication of trauma to the cervical spine.
      Symptoms of spinal cord injury, however, may obscure those of vertebral artery
      dissection, presumably causing gross underdiagnosis of this complication.
      METHODS: All patients with vertebral artery dissection admitted to the authors'
      facility between 1992 and 1997 were screened for cervical trauma. RESULTS: This
      article presents four patients with severe trauma to the cervical spine, defined
      as luxation, subluxation, or fracture, in whom symptoms of vertebral artery
      dissection developed after a delay ranging from several hours to weeks. The
      traumatic vertebral artery dissection typically was located at the site of
      vertebral injury or cranial to it. One patient with fracture of the odontoid
      process survived symptom free without ischemic brain infarctions. Another patient
      survived with traumatic quadriplegia in addition to large cerebellar and
      posterior cerebral artery infarctions. Two patients died as a result of fulminant
      vertebrobasilar infarctions, both with only moderate impairment from the primary
      spinal cord injury. CONCLUSIONS: Early signs of vertebral artery dissection
      include head and neck pain, often localized to the site of intimal disruption,
      which may be disguised by the signs of the spinal injury. Early Doppler
      ultrasound and duplex sonography as a noninvasive screening method should be
      performed for patients with severe trauma to the cervical spine. In cases of
      vertebral artery dissection, immediate anticoagulation should be initiated.
      Traumatologists should be aware of this complication in evaluating patients with
      severe trauma of the cervical spine, and also for a variety of forensic reasons.

PMID- 11224871
TI  - Symposium: a critical discrepancy-a criteria of successful arthrodesis following
      interbody spinal fusions.

PMID- 11224872
TI  - The relative roles of intragenic polymorphisms of the vitamin d receptor gene in
      lumbar spine degeneration and bone density.
AB  - STUDY DESIGN: A retrospective cohort study. OBJECTIVES: To compare the magnitudes
      of the associations of TaqI polymorphisms of the vitamin D receptor gene with
      bone density and lumbar spine degeneration in the same sample. SUMMARY OF
      BACKGROUND DATA: Vitamin D receptor gene variations are associated with
      osteoporosis, osteoarthritis, and disc degeneration. Their role in these
      conditions remains poorly understood. METHODS: Bone density of the spine and
      femur were determined through DEXA, and lumbar disc degeneration was determined
      from magnetic resonance imaging assessments of signal intensity, disc narrowing,
      bulging, anular tears, herniations, and osteophytes. Associations between these
      measures and TaqI polymorphisms of the coding region of the Vitamin D receptor
      locus were examined in a population-based sample of 142 men. RESULTS: The
      strongest associations were with signal intensity and anular tears, which were
      worse for the subjects with tt genotypes than for those with TT genotypes in the
      L4-S1 spine discs. Conversely, the prevalences of disc bulges and osteophytes
      were lowest for the tt genotype. Bone density, disc height, and herniations did
      not differ significantly by genotype. CONCLUSIONS: The strongest association of
      Vitamin D receptor TaqI polymorphisms with degeneration in nonmineralized
      connective tissues suggests that the underlying mechanism of TaqI polymorphisms
      is not specific to bone. This study demonstrated for the first time that those
      with the tt genotype had more anular tears than those with the TT genotype, a
      finding that should stimulate further analyses of this gene in conditions that
      result in back pain. The apparent discrepancies of the associations of the tt
      genotype with lower signal intensity and more anular tears, but less bulges and
      osteophytes, could be explained if bulging and osteophytes primarily represented
      remodeling related to lifetime physical loading.

PMID- 11224873
TI  - Quantitative changes in spinal canal dimensions using interbody distraction for
      spondylolisthesis.
AB  - STUDY DESIGN: An experimental study was performed using cadaveric lumbar spines
      to evaluate the effect of anteriorly or laterally placed interbody distraction
      implants on the alteration of spinal canal and neuroforaminal dimensions.
      OBJECTIVES: To quantify changes in the spinal canal and neuroforaminal dimensions
      using interbody fusion devices inserted at various configurations in cadaveric
      lumbar spines exhibiting degenerative spondylolisthesis. SUMMARY OF BACKGROUND
      DATA: Although several clinical studies have demonstrated successful treatment of
      degenerative spondylolisthesis with anterior interbody fusion, no study has shown
      the role of interbody distraction in improving lumbar spinal canal and foraminal
      stenosis. METHODS: Five fresh cadaver lumbar spines exhibiting a degenerative
      spondylolisthesis or retrospondylolisthesis were used for the study. Computed
      tomography scans of each specimen and a silicon mold of the left intervertebral
      foramens were repeated in a consistent manner after pure compressive load (150
      lb) was applied to simulate physiologic load (intact case), after two BAK (Sulzer
      SpineTech Inc., Minneapolis, MN) distraction plugs were anteriorly inserted into
      the intervertebral disc space (anterior distraction cases), and after one long
      BAK cage was laterally inserted from the left side (lateral distraction case).
      The cross-sectional area of the spinal canal was measured from computed
      tomography images using National Institutes of Health image software (Bethesda,
      MD). The spinal canal volume was calculated using the cross-sectional area and
      total scan thickness. Left intervertebral foraminal volumes were calculated from
      the weight of the silicon mold injected into the foramen. Descriptive statistics
      and a Student's t test were used to detect statistical differences in the spinal
      canal and neuroforaminal volumes before and after interbody distraction. RESULTS:
      The cross-sectional canal area was significantly increased after anterior
      distraction (35.11%) and lateral distraction (33.14%). The spinal canal volume
      was markedly increased with anterior distraction (19.92%) and lateral distraction
      (21.96%). Left foraminal volume was also enhanced by 40.25% for anterior
      distraction and 41.03% for lateral distraction. CONCLUSIONS: Interbody
      distraction either by anteriorly inserted plugs or laterally inserted threaded
      cagescan immediately improve the narrowed canal area and increase spinal canal,
      as well as foraminal volume for lumbar degenerative spondylolisthesis or retro-
      spondylolisthesis.

PMID- 11224875
TI  - Endocrine and immunologic parameters indicative of 6-month prognosis after the
      onset of low back pain or neck/shoulder pain.
AB  - STUDY DESIGN: Prospective study. OBJECTIVES: To evaluate the prognosis of spine
      disease by investigating biologic parameters reflecting different physiologic or
      psychophysiological systems in men and women with acute onset of low back or
      neck/shoulder complaints. SUMMARY OF BACKGROUND DATA: Psychosocial factors may be
      of importance to the etiology and prognosis of musculoskeletal disorders. The
      possible mechanisms, however, remain unclear. Stress-induced long-lasting energy
      mobilization resulting in inhibited anabolism has been discussed. Using a
      theoretical framework within stress physiology, such psychophysiological
      processes were recorded by measures of substances representing the anabolic,
      catabolic, immunologic, and opioid systems. METHODS: The study comprised 67
      working men and women 21 to 59 years of age seeking care by any caregiver for
      acute low back and/or neck/shoulder pain. Blood samples were taken and analyzed
      for 3 methyl 5hydroxy phenylethylene glycol (MHPG, reflecting
      sympathoadrenomedullary activity), DHEA-s (anabolism), immunoglobulin E,
      interleukin 6 (immune activity), and beta-endorphin (pain regulation). The
      participants were followed up for 6 months after the blood samples had been
      drawn. RESULTS: In women, low MHPG, low DHEA-s, and low beta-endorphin predicted
      persistent disability due to low back complaints. Few significant findings were
      made for self-reported pain, for neck/shoulder complaints, and for men.
      CONCLUSION: Disturbances of the regulation of certain biologic parameters might
      be indicators of a prolonged course of low back disease in women. Prospective
      studies are necessary to enable causal conclusions.

PMID- 11224874
TI  - Osteopenia in adolescent idiopathic scoliosis: a histomorphometric study.
AB  - STUDY DESIGN: Bone biopsies from iliac crest and spinous process of adolescent
      idiopathic scoliosis patients were obtained intraoperatively for histology and
      histomorphometric analysis. OBJECTIVES: To study the histologic features of
      cancellous bone and to correlate the histomorphometric variables with
      preoperative bone mineral density in patients with adolescent idiopathic
      scoliosis. SUMMARY OF BACKGROUND DATA: Low bone mineral density has been reported
      in adolescent idiopathic scoliosis. However, there is limited information about
      the histopathologic changes. METHODS: Undecalcified and decalcified bone
      specimens from iliac crest and spinous process of adolescent idiopathic scoliosis
      patients obtained intraoperatively were stained with Goldner and hematoxylin &
      eosin stain, respectively. Results were correlated with bone mineral density of
      the lumbar spine (L2-L4) and proximal femur measured before surgery. RESULTS:
      Bone histology showed significant less osteocyte count in the trabecular bone
      characterized with smooth and continuous borders in patients with adolescent
      idiopathic scoliosis. Histomorphometry confirmed the lower static parameters. The
      results correlated well with the decreased bone mineral density. CONCLUSION: Bone
      biopsy study suggested disturbance of bone turnover in patients with adolescent
      idiopathic scoliosis. The abnormal metabolism might contribute to the low bone
      mineral density and play an important role in the etiology and pathogenesis of
      adolescent idiopathic scoliosis.

PMID- 11224876
TI  - Vacuum-assisted wound closure: a new approach to spinal wounds with exposed
      hardware.
AB  - STUDY DESIGN: The use of vacuum-assisted therapy to close upper thoracic and
      thoracolumbar spinal wounds was studied retrospectively. Two patients whose
      wounds failed conservative management were successfully treated by negative
      pressure therapy. OBJECTIVES: The authors evaluated the efficacy of applying
      vacuum therapy on patients with exposed spinal hardware and summarized current
      knowledge about this treatment. SUMMARY OF BACKGROUND DATA: Vacuum therapy was
      applied three times on two patients. METHODS: Success was defined as a stable,
      closed wound that required no future surgery and had no signs of chronic
      infection. RESULTS: Both patients' wounds were closed successfully and have
      received follow-up treatment for up to 10 months with no sign of recurrence.
      CONCLUSIONS: The cases illustrate the usefulness of vacuum-assisted therapy as an
      adjunct in closing complex back wounds with exposed spinal hardware. In the
      authors' experience, it helps establish a soft tissue envelope for wound healing
      and simplifies the need for future surgery.

PMID- 11224879
TI  - The cause of neurologic deterioration after acute cervical spinal cord injury.
AB  - STUDY DESIGN: A retrospective review was performed to identify patients at risk
      for secondary neurologic deterioration after complete cervical spinal cord
      injury. OBJECTIVE: To examine the causes of early neurologic deterioration in
      patients with complete spinal cord injury at a regional spinal cord injury
      center. SUMMARY OF BACKGROUND DATA: After complete spinal cord injury, neurologic
      deterioration occurs in a subgroup of patients. Despite anecdotal reports, no
      study has clearly identified the subgroups at highest risks. METHODS: One hundred
      eighty-two patients with complete spinal cord injury were identified among 1904
      consecutive patients with acute spinal trauma evaluated from March 1993 through
      September 1999. Parameters analyzed included demographics, mechanism of injury,
      American Spinal Cord Injury Association (ASIA) level on admission and during
      hospital stay, onset of ascension, blood pressure, hemoglobin, febrile episode,
      heparin administration, and the timing of operation and traction. Radiographs of
      patients with ascending complete spinal cord injury were reviewed with attention
      to fracture type and neurologic and vascular injuries. RESULTS: Twelve of 186
      patients with ASIA Grade A (6.0%) complete spinal cord injury had neurologic
      deterioration during the first 30 days after injury. No patients with penetrating
      injuries had deterioration. A significant association between death and ascension
      was observed. The onset of ascension of the injury could be categorized into
      three discrete temporal subsets. Early deterioration (less than 24 hours) was
      typically related to traction and immobilization. Delayed deterioration (between
      24 hours and 7 days) was associated with sustained hypotension in patients with
      fracture dislocations. Late deterioration (more than 7 days) was observed in a
      patient with vertebral artery injuries. CONCLUSION: Delayed neurologic
      deterioration in complete spinal cord injury (ASIA A) is not rare. Specific
      causes were identified among discrete temporal subgroups. Management of complete
      spinal cord injury can be improved with recognition of these temporal patterns
      and earlier intervention.

PMID- 11224880
TI  - Virtual fluoroscopy: computer-assisted fluoroscopic navigation.
AB  - STUDY DESIGN: In vitro accuracy assessment of a novel virtual fluoroscopy system.
      OBJECTIVES: To investigate a new technology combining image-guided surgery with C
      arm fluoroscopy. SUMMARY OF BACKGROUND DATA: Fluoroscopy is a useful and familiar
      technology to all musculoskeletal surgeons. Its limitations include radiation
      exposure to the patient and operating team and the need to reposition the
      fluoroscope repeatedly to obtain surgical guidance in multiple planes. METHODS:
      Fluoroscopic images of the lumbar spine of an intact, unembalmed cadaver were
      obtained, calibrated, and saved to an ). A was used for the sequential insertion
      of a light-emitting diode-fitted probe into the pedicles of L1-S1 bilaterally.
      The trajectory of a "virtual tool" corresponding to the tracked tool was overlaid
      onto the saved fluoroscopic views in real time. Live fluoroscopic images of the
      inserted pedicle probe were then obtained. Distances between the tips of the
      virtual and fluoroscopically displayed probes were quantified using the image
      guided computer's measurement tool. Trajectory angle differences were measured
      using a standard goniometer and printed copies of the workstation computer
      display. The surgeon's radiation exposure was measured using thermolucent
      dosimeter rings. RESULTS: Excellent correlation between the virtual fluoroscopic
      images and live fluoroscopy was observed. Mean probe tip error was 0.97 +/- 0.40
      mm. Mean trajectory angle difference between the virtual and fluoroscopically
      displayed probes was 2.7 degrees +/- 0.6 degrees. The thermolucent dosimeter
      rings measured no detectable radiation exposure for the surgeon. CONCLUSIONS:
      Virtual fluoroscopy offers several advantages over conventional fluoroscopy while
      providing acceptable targeting accuracy. It enables a single C-arm to provide
      real-time, multiplanar procedural guidance. It also dramatically reduces
      radiation exposure to the patient and surgical team by eliminating the need for
      repetitive fluoroscopic imaging for tool placement.

PMID- 11224881
TI  - Accuracy requirements for image-guided spinal pedicle screw placement.
AB  - STUDY DESIGN: Accuracy requirement analysis for image-guided pedicle screw
      placement. OBJECTIVES: To derive theoretical accuracy requirements for image
      guided spinal pedicle screw placement. SUMMARY OF BACKGROUND DATA: Underlying
      causes of inaccuracy in image-guided surgical systems and methods for quantifying
      this inaccuracy have been studied. However, accuracy requirements for specific
      spinal surgical procedures have not been delineated. In particular, the accuracy
      requirements for image-guided spinal pedicle screw placement have not been
      previously reported. METHODS: A geometric model was developed relating spinal
      pedicle anatomy to accuracy requirements for image-guided surgery. This model was
      used to derive error tolerances for pedicle screw placement when using clinically
      relevant screw diameters in the cervical (3.5 mm), thoracic (5.0 mm), and
      thoracolumbar spine (6.5 mm). The error tolerances were represented as the
      permissible rotational and translational deviations from the ideal screw
      trajectory that would avoid pedicle wall perforation. The relevant dimensions of
      the pedicle model were extracted from existing morphometric data. RESULTS: As
      anticipated, accuracy requirements were greatest at spinal levels where the
      relevant screw diameter approximated the dimensions of the pedicle. These
      requirements were highest for T5, followed in descending order by T4, T7, T6, T3,
      T12, L1, T8, T11, C4, L2, C3, T10, C5, T2, T9, C6, L3, C2, T1, C7, L4, and L5.
      Maximum permissible translational/rotational error tolerances ranged from 0.0
      mm/0.0 degrees at T5 to 3.8 mm/12.7 degrees at L5. CONCLUSIONS: These results,
      obtained by mathematical analysis, demonstrate that extremely high accuracy is
      necessary to place pedicle screws at certain levels of the spine without
      perforating the pedicle wall. These accuracy requirements exceed the accuracy of
      current image-guided surgical systems, based on clinical utility errors reported
      in the literature. In actual use, however, these systems have been shown to
      improve the accuracy of pedicle screw placement. This dichotomy indicates that
      other factors, such as the surgeon's visual and tactile feedback, may be
      operative.

PMID- 11224882
TI  - Computer-assisted thoracic pedicle screw placement: an in vitro feasibility
      study.
AB  - STUDY DESIGN: In this cadaveric study, a computer-assisted image guidance system
      was tested for accuracy of thoracic pedicle screw placement. OBJECTIVES: Evaluate
      the system's accuracy for thoracic pedicle screw placement in vitro. SUMMARY OF
      BACKGROUND DATA: The effective use and reliability of pedicle screw
      instrumentation in providing short-segment stabilization and correction of
      deformity is well known in the lumbar spine. Pedicle screw placement in the
      thoracic spine is difficult because of the small dimensions of the thoracic
      pedicles and risk to the adjacent spinal cord and neurovascular structures.
      Investigators have shown the improved accuracy of computer-assisted lumbar
      pedicle screw placement; but the accuracy of computer-assisted thoracic pedicle
      screw placement, which is becoming more widely used, has not been shown. METHODS:
      In five human cadavers, 120 thoracic pedicle screws were placed with computer
      assisted image guidance. The largest clinically feasible screw was used based on
      the cross-sectional dimensions of each pedicle. The accuracy was assessed by
      postoperative computed tomography and visual inspection. RESULTS: The overall
      pedicle cortex violation was 23 of 120 pedicles (19.2%). Nine violations (7.5%)
      were graded as major and 14 (11.7%) as minor. A marked and progressive learning
      curve was evident with the perforation rates that decreased from 37.5% in the
      first cadaver to 4.2% in the last two cadavers. CONCLUSIONS: Accurate thoracic
      pedicle screw placement is feasible with computer-assisted surgery. However, as
      with any other new surgical technology, the learning curve must be recognized and
      incorporated into the necessary fundamental knowledge and experience for these
      procedures.

PMID- 11224883
TI  - Computer-assisted orthopedic surgery with individual templates and comparison to
      conventional operation method.
AB  - STUDY DESIGN: Comparison was made of the accuracy of a pedicle bore performed by
      conventional technique and by using an individual template in the lumbar spine of
      cadavers. OBJECTIVES: The fixation of pedicle screws necessitates a high amount
      of surgical skill and experience to avoid lesions of nerves and vessels. By using
      individual templates in a cadaver study the goal was to prove the accuracy and
      efficiency of this less-invasive image-guided surgery in comparison with the
      conventional technique by fluoroscopy and computed tomographic (CT) scan. SUMMARY
      OF BACKGROUND DATA: Based on three-dimensional models generated from CT scans of
      the lumbar spine, precise preoperative planning of the position and trajectory of
      pedicle screws is possible. In comparison with other means of computer-assisted
      spine surgery with navigation systems, in which a time-consuming intraoperative
      matching of the bone surface structure is necessary, the use of individual
      templates enables the surgeon to reduce the operation time considerably. METHODS:
      Individual templates are customized on the basis of three-dimensional
      reconstructions of the bone structures extracted from CT image data and depending
      on the individual preoperative surgical planning, which uses the desktop image
      processing system for orthopedic surgery (DISOS). A desktop-computer-controlled
      milling device is used as a three-dimensional printer to automatically mold the
      shape of small reference areas of the bone surface into the body of the template.
      Postoperative CT scans were obtained and the accuracy of the pedicle bore rated
      by two independent observers. RESULTS: The preparation time with the individual
      template lasted slightly longer than with the conventional operation technique
      (555 seconds and 482 seconds, respectively). Fluoroscopic study took a mean time
      of 31.5 seconds, with the conventional operation technique and 5.5 seconds with
      the individual template. The assessment of the postoperative CT scans
      demonstrated a higher accuracy of the pedicle bore with the individual template.
      CONCLUSIONS: This cadaveric study has shown that overall operation time including
      the fluoroscopy time can be shortened by using the individual template for the
      pedicle bore. The individual template is an alternative to the computer-assisted
      navigation systems with a good cost-performance ratio without excessive technical
      workload on the physicians or the surgical personnel. Further investigations must
      be conducted to validate the clinical applicability of this system.

PMID- 11224884
TI  - The significance of thoracolumbar spinal canal size in spinal cord injury
      patients.
AB  - STUDY DESIGN: A prospective, consecutive case series. OBJECTIVES: To determine
      the relation between spinal canal dimensions and Injury Severity Score and their
      association with neurologic sequelae after thoracolumbar junction burst fracture.
      SUMMARY OF BACKGROUND DATA: There is a relation in the cervical spine between
      spinal canal dimension and its association with neurologic sequelae after trauma.
      A similar relation at the thoracolumbar junction has not been conclusively
      established. METHODS: Forty-three patients with thoracolumbar junction burst
      fractures (T12-L2),13 with and 30 without neurologic deficit, were included.
      Computed tomographic scans were used to measure the sagittal and transverse
      diameters and the surface area of the spinal canal at the level of injury, as
      well as one level above and one level below the fracture level. Injury severity
      score was calculated for both groups. Statistical analysis comparing those with a
      neurologic deficit to those without was performed by Student's t test. RESULTS:
      The ratio of sagittal-to-transverse diameter at the level of injury was
      significantly smaller in patients with a neurologic deficit than in those without
      a neurologic deficit (P < 0.05). The mean transverse diameter at the level of
      injury was significantly larger in patients with neurologic deficit than in the
      neurologically intact patients (P < 0.05). The surface area of the canal at the
      level below the injury was significantly larger in the patients with a neurologic
      deficit than in those without a deficit (P < 0.05). Patients with a neurologic
      deficit had a statistically higher Injury Severity Score when admitted than those
      without a neurologic deficit (P < 0.0001), although the difference became
      insignificant after the neurologic component of the scoring system was
      eliminated. CONCLUSION: There are no anatomic factors at the thoracolumbar
      junction that predispose to neurologic injury after burst fracture. The shape of
      the canal after injury, however, as determined by the sagittal-to-transverse
      diameter ratio, was predictive of neurologic deficit.

PMID- 11224885
TI  - Lumbar supports for prevention and treatment of low back pain: a systematic
      review within the framework of the Cochrane Back Review Group.
AB  - STUDY DESIGN: A systematic review of randomized and nonrandomized controlled
      trials. SUMMARY OF BACKGROUND DATA: Lumbar supports are used in the treatment of
      low back pain, but also to prevent the onset (primary prevention) or recurrences
      of a low back pain episode (secondary prevention). OBJECTIVES: To assess the
      effects of lumbar sup-ports for prevention and treatment of nonspecific low back
      pain. METHODS: The Medline, Cinahl, and Current Contents databases; the Cochrane
      Controlled Trials Register up to September 1999; and the Embase database up to
      September 1998 were all searched. References of identified trials and systematic
      reviews were reviewed and the Science Citation Index used to identify additional
      trials. Methodologic quality assessment and data extraction were performed by two
      reviewers independently. A quantitative analysis was performed in which the
      strength of evidence was classified as strong, moderate, limited or conflicting,
      and no evidence. RESULTS: Five randomized and two nonrandomized preventive trials
      and six randomized therapeutic trials were included in the review. Only 4 of the
      13 studies were of high quality. There was moderate evidence that lumbar supports
      are not effective for primary prevention. No evidence was found on the
      effectiveness of lumbar supports for secondary prevention. The systematic review
      of therapeutic trials showed that there is limited evidence that lumbar supports
      are more effective than no treatment, whereas it is still unclear whether lumbar
      supports are more effective than other interventions for treatment of low back
      pain. CONCLUSIONS: There continues to be a need for high quality randomized
      trials on the effectiveness of lumbar supports. One of the most essential issues
      to tackle in these future trials seems to be the realization of adequate
      compliance.

PMID- 11224886
TI  - Evidence of lung injury during reconstructive surgery for adult spinal
      deformities with pulmonary artery pressure monitoring.
AB  - STUDY DESIGN: Observational analyses of 55 adult patients who underwent elective
      sequential anterior-posterior thoracolumbosacral surgical corrections for spinal
      deformities were used to evaluate the efficacy of pulmonary artery catheter
      monitoring. OBJECTIVE: To demonstrate that during complex reconstructive surgery
      for spinal deformities, pulmonary artery catheter monitoring identifies a subset
      of patients with pulmonary injury and is essential in their management. SUMMARY
      OF BACKGROUND DATA: Patients who undergo sequential anterior-posterior
      thoracolumbosacral surgical corrections for spinal deformities experience
      significant perioperative morbidity. Although the value of pulmonary artery
      catheter monitoring is controversial, its use in these procedures may help
      identify potential physiologic complications and improve surgical outcome.
      METHODS: All patients were monitored with a pulmonary artery catheter during
      surgery until at least postoperative day 1. Outcome measurements included blood
      loss, vertebral levels fused, operative time, postoperative respiratory
      complications, and days in intensive care. RESULTS: Eight (8/55; 14.5%) patients
      according to pulmonary artery catheter monitoring demonstrated elevated pulmonary
      vascular resistance and noncardiac pulmonary edema. These patients had longer
      operative procedures with greater blood loss and had more postoperative
      respiratory complications. They were treated appropriately in intensive care and
      discharged without further complications. CONCLUSION: Pulmonary artery catheter
      monitoring of patients who undergo complex spinal fusion facilitates the
      identification of patients with pulmonary injury and is essential in the
      management of these patients in the postoperative period. It may, also, be a
      marker for embolic injury to the lung.

PMID- 11224887
TI  - Closing-opening wedge osteotomy to correct angular kyphotic deformity by a single
      posterior approach.
AB  - STUDY DESIGN: Seven patients with angular kyphotic deformity of the thoracic or
      thoracolumbar spine were treated by closing-opening wedge osteotomy using a
      single posterior approach. OBJECTIVES: To examine the safety and efficacy of
      closing-opening wedge osteotomy for angular kyphosis. SUMMARY OF BACKGROUND DATA:
      Correction osteotomy of severe kyphosis is a challenging operation. A two-stage
      operation has been commonly used: anterior release and decompression followed by
      posterior correction and fusion. METHODS: Seven patients with angular kyphosis
      were treated. The apex level of kyphosis was T5 in one patient, T11 in one, and
      T12 in five. There was old fracture in five patients, congenital deformity in
      one, and neurofibromatosis in one. The first 30-35 degrees of kyphosis are
      corrected using the closing wedge technique with the hinge of the anterior
      longitudinal ligament after veretebrectomy and circumspinal decompression of the
      spinal cord. Then the hinge is moved posteriorly to the spinal cord and the
      remainder of the requisit angle of osteotomy is corrected using the opening-wedge
      technique (closing-opening wedge osteotomy). Spinal curvature is stabilized using
      posterior instrumentation and graft. RESULTS: Localized kyphosis was reduced from
      an average of 67 degrees to 18 degrees at 2.2 to 7.5 years' follow-up. Sagittal
      alignment from T1 to the sacrum became more physiologic than before. There were
      no neurologic complications. Bony fusion was achieved in all patients, and there
      was no correction loss. CONCLUSIONS: Satisfactory correction is safely performed
      by closing-opening wedge osteotomy with a direct visualization of the
      circumferentially decompressed spinal cord. Although the performance is
      technically laborious, it offers good correction without jeopardizing the
      integrity of the spinal cord.

PMID- 11224888
TI  - Thoracolumbar spinal abnormalities in Stickler syndrome.
AB  - STUDY DESIGN: Retrospective review of clinical and radiographic records of
      patients with Stickler syndrome. OBJECTIVES: To describe thoracolumbar spinal
      abnormalities and their correlation with age and back pain among patients with
      Stickler syndrome. SUMMARY OF BACKGROUND DATA: Stickler syndrome (hereditary
      arthro-ophthalmopathy) is an autosomal dominant connective tissue disorder
      characterized by skeletal, ocular, oral-facial, cardiac, and auditory
      manifestations. Prevalence is approximately 1 in 10,000 (similar to that of
      Marfan syndrome). No one has investigated spinal abnormalities in a large series
      of patients. METHODS: A single-center evaluation of 53 patients from 24 families
      with Stickler syndrome (age range, 1-70 years) in a multidisciplinary genetics
      clinic. Thoracolumbar radiographs were analyzed for spinal abnormalities and
      correlation with age and back pain. RESULTS: Thirty-four percent of patients had
      scoliosis, 74% endplate abnormalities, 64% Schmorl's nodes, 43% platyspondylia,
      and 43% Scheuermann-like kyphosis. Sixty-seven percent of patients and 85% of
      adults reported chronic back pain. Endplate abnormalities and Schmorl's nodes
      were associated with adult age; endplate abnormalities, Schmorl's nodes, and
      adult age were associated with back pain. Only one adult patient was free of
      spinal abnormalities. CONCLUSIONS: Spinal abnormalities are nearly uniformly
      observed in Stickler syndrome, progress with age, and are associated with back
      pain. Although common, scoliosis is generally self-limited (only one patient
      needed surgical treatment). Correct diagnosis of this syndrome facilitates early
      identification and management of other potentially severe systemic manifestations
      and genetic counseling for affected families. Moreover, recognition of Stickler
      syndrome allows accurate prognosis for skeletal abnormalities and anticipation of
      potential surgical complications.

PMID- 11224889
TI  - Initial experience with intraoperative magnetic resonance imaging in spine
      surgery.
AB  - STUDY DESIGN: A case series of 12 patients who underwent spine surgery in an
      intraoperative magnetic resonance imager (IMRI). OBJECTIVES: To determine the
      advantages, limitations, and potential applications to spine surgery of the IMRI.
      SUMMARY OF BACKGROUND DATA: Existing stereotactic navigational systems are
      limited because images are obtained before surgery and are not updated to reflect
      intraoperative changes. In addition, they necessitate manual registration of
      fiducial landmarks on the patient's anatomy by the surgeon to the previously
      obtained image data set, which is a potential source of error. The IMRI
      eliminates these difficulties by using intraoperative acquisition of MRI images
      for surgical navigation with the capacity for both image update and image-guided
      frameless stereotaxy. The IMRI is a novel cryogenless superconducting magnet with
      an open configuration that allows the surgeon full access to the patient during
      surgery and intraoperative imaging. METHODS: T1- and T2-weighted fast spin echo
      images were obtained for localization, after surgical exposure and after
      decompression during the course of 12 spine surgeries performed in the IMRI.
      RESULTS: The authors performed a series of 12 procedures in the IMRI that
      included three lumbar discectomies, three anterior cervical discectomies with
      allograft fusion, three cervical vertebrectomies with allograft fusion, two
      cervical foraminotomies, and one decompressive cervical laminectomy. The system
      provided rapid and accurate localization in all cases. The adequacy of
      decompression by MRI during surgery was confirmed in 10 of 12 cases. CONCLUSIONS:
      The IMRI provided accurate and rapid localization in all cases and confirmed the
      adequacy of decompression in the majority of cases. Future applications of the
      IMRI to spine surgery may include intraoperative guidance for resection of spine
      and spinal cord tumors and trajectory planning for spinal endoscopy or screw
      fixation.

PMID- 11224890
TI  - Timing of activation of the erector spinae and hamstrings during a trunk flexion
      and extension task.
AB  - STUDY DESIGN: Timing of activation of the hamstrings and erector spinae was
      assessed using surface electromyography. OBJECTIVES: To investigate the influence
      of posture and movement speed during trunk flexion-extension on the flexion
      relaxation response and trunk muscle activation patterns. SUMMARY OF BACKGROUND
      DATA: The literature contains numerous reports on coactivity and synergistic
      behavior of major muscle groups during trunk flexion-extension. There are few
      reports on the timing of muscle activation. METHODS: Six subjects were recruited
      for a training session and six biweekly test sessions. Ten surface electromyogram
      electrodes and a lordosimeter were used to record timing of lumbar motion and
      muscle recruitment in the hamstrings and at four sites in the thoracolumbar
      region. A 3 x 2 within-subject factorial design was used to test the effects of
      posture and speed on activation patterns. RESULTS: Patterns of muscle activation
      were found to be dependent on posture and the direction of movement. The flexion
      relaxation response was pervasive in the lumbar region but was less consistent at
      the T9 and hamstring sites. Significant differences in the delay between
      electromyogram activation and lumbar motion were found for the standing postures
      at initiation of extension, in which activation progressed in the caudad-to
      cephalad direction. CONCLUSIONS: The flexion-relaxation response is ubiquitous in
      the lumbar erector spinae and is present in the hamstrings and lower thoracic
      erector spinae, although not consistently in all subjects. In standing, timing of
      activation differed significantly by site in extension but not in flexion. Muscle
      activation patterns and flexion-relaxation were consistent over six biweekly test
      sessions.

PMID- 11224891
TI  - Early complications of high-dose methylprednisolone sodium succinate treatment in
      the follow-up of acute cervical spinal cord injury.
AB  - STUDY DESIGN: A prospective, randomized, and double-blind study comparing high
      dose methylprednisolone sodium succinate (MPSS) with placebo, in the treatment of
      patients with acute cervical spinal cord injury. OBJECTIVES: To evaluate the
      complications of high-dose MPSS in patients with acute cervical spinal cord
      injury when administered within 8 hours of injury. SUMMARY OF BACKGROUND DATA:
      High-dose therapy with MPSS has been demonstrated to improve the recovery of
      motor function in patients with acute cervical spinal cord injury. However,
      little is known about the follow-up complications. METHODS: Forty-six patients,
      42 men and 4 women (mean age, 60.6 years; range, 18-84), were included in the
      study: 23 in the MPSS group and 23 in the placebo group. They were treated
      without surgery for spinal cord injury in the cervical spine, and were enrolled
      in the trial if a diagnosis had been made and treatment had begun within 8 hours.
      Complications of high-dose therapy with MPSS were compared with placebo treatment
      throughout the study period and up to 2 months after injury. RESULTS: The MPSS
      group had 13 patients (56.5%) with complications, whereas the placebo group had 8
      (34.8%). The difference between the two groups was not statistically significant
      (P = 0.139). There were eight instances of pulmonary complication with MPSS
      (34.8%) and one instance (4.34%) with placebo (P = 0.009). There were four
      instances of gastrointestinal complication (17.4%) with MPSS and none with
      placebo (P = 0.036). Pulmonary (complications were more prevalent in patients
      aged more than 60 years (P = 0.029). CONCLUSION: Aged patients with cervical
      spinal injury may be more likely to have pulmonary side effects (P = 0.029) after
      high-dose therapy with MPSS and thus deserve special care.

PMID- 11224892
TI  - Reconstruction after total en bloc sacrectomy for osteosarcoma using a custom
      made prosthesis: a technical note.
AB  - STUDY DESIGN: A report of an innovative technique to restore the lumbosacral
      junction after resection of primary highly malignant osteosarcoma of the sacrum
      involving the whole sacrum, soft tissues, and adjacent posterior parts of both
      iliac wings. OBJECTIVES: To describe the planning and design of a custom-made
      sacral prosthesis, the surgical technique, and clinical and functional outcome of
      the patient. SUMMARY OF BACKGROUND DATA: Although there have been case reports
      about reconstruction methods after total sacrectomy, to date, there has not been
      a reported clinical case of successful reconstruction using an individual
      designed prosthesis based on a three-dimensional real-sized model. METHODS: A 42
      year-old woman was referred with progressive neurologic impairment due to primary
      osteosarcoma of the sacrum invading surrounding structures. Based on a three
      dimensional real-sized model, a detailed surgical plan was developed to assure
      safe, wide surgical margins. In addition, the model enabled design and testing of
      a custom-made sacral prosthesis, to provide stable lumbosacral reconstruction.
      RESULTS: After induction chemotherapy, a staged anteroposterior resection
      reconstruction was successfully performed. After surgery, a superficial wound
      dehiscence was promptly treated. Within 3 weeks after surgery, mobilization
      began, and the adjuvant chemotherapy was continued. At the 36-month follow-up,
      the patient was disease free, had a stable, painless spinopelvic junction, and
      could walk short distances using ankle orthoses and crutches. Radiographs show
      complete incorporation of the pelvic grafts and unchanged position of the
      implant. CONCLUSIONS: In planning and performing a total sacrectomy, including
      substantial parts of iliac wings, a three-dimensional real-sized model offers
      surgeons distinct advantages. Wide bony resection margins can be drawn on the
      model, and an individual custom-made prosthesis to re-establish spinopelvic
      continuity can be designed and tested before the intervention.

PMID- 11224893
TI  - Surgery for lumbar disc herniation during pregnancy.
AB  - STUDY DESIGN: The case reports of three pregnant patients with lumbar disc
      herniation causing cauda equina syndrome or severe neurologic deficits are
      presented to illustrate that disc surgery during gestation is a safe method of
      management. OBJECTIVE: To emphasize the importance of recognizing and
      definitively treating lumbar disc displacement causing neurologic deficits during
      pregnancy. SUMMARY OF BACKGROUND DATA: The advent of magnetic resonance imaging
      and modern surgical techniques for treatment of lumbar disc displacement allows
      safe management of this condition at any stage of gestation. A review of the
      literature on the risks of nonobstetric surgery and the risks of delaying disc
      surgery until delivery shows that operating at any stage during gestation for
      severe neurologic deficit secondary to lumbar disc displacement is justified.
      METHODS: A review of the literature on the use of magnetic resonance imaging scan
      and nonobstetric surgery during pregnancy was performed. Three case reports of
      the authors' patients who had lumbar disc displacement with cauda equina syndrome
      or severe neurologic deficit are presented. Patients were placed prone on a four
      poster frame, and an epidural anesthetic agent was administered. A one-level
      hemilaminectomy, partial facetectomy, and disc excision were performed in all
      three cases. RESULTS: The methods used for diagnosis and surgical treatment of
      three patients with disc herniation during pregnancy resulted in a satisfactory
      outcome for both mother and child. The medical literature supports surgical
      intervention in pregnant patients with cauda equina syndrome and severe and/or
      progressive neurologic deficit(s) from lumbar disc displacement at any state of
      gestation. CONCLUSION: Although extremely rare, cauda equina syndrome and severe
      and/or progressive neurologic deficit caused by lumbar disc displacement can
      occur during pregnancy. The prevalence of symptomatic lumbar disc herniation
      during pregnancy may be on the increase because of the increasing age of patients
      who are becoming pregnant. These cases showed, and the literature confirms, that
      pregnancy at any stage is no contraindication to magnetic resonance imaging scan,
      epidural and/or general anesthesia, and surgical disc excision.

PMID- 11224894
TI  - An unusual stab wound of the cervical spinal cord: a case report.
AB  - STUDY DESIGN: A rare case of a laterally directed stab wound injury of the
      cervical spinal cord is reported. OBJECTIVE: To describe the unusual mechanism of
      injury of this case and its clinical features. The surgical indications for
      penetrating injuries of the spinal cord are discussed. SUMMARY OF BACKGROUND
      DATA: Spinal stab wound injuries are rare, and the literature on the subject is
      scant. There has been only one large clinical review from South Africa, published
      in 1977. The clinical features and the injury mechanism of a laterally directed
      stab wound to the cervical spine have not been previously described. METHODS: An
      18-year-old man was stabbed in the right side of the neck at C1-C2. The blade
      penetrated the spine laterally and went through the ligaments without affecting
      the bony structures. On admission the patient had tetraplegia and was in
      respiratory failure. Radiologic investigation showed the retained blade passing
      through the cord but showed no bony or vascular injuries. RESULTS: Before
      extraction, the knife was followed to its tip with careful dissection. Because no
      cerebrospinal fluid leak was noted in the area, the dura was not exposed. After
      surgery, magnetic resonance images showed a complete transection of the spinal
      cord at C1-C2. The patient was neurologically unchanged in follow-up
      examinations. CONCLUSION: Laterally directed horizontal stab wounds of the spine
      are particularly dangerous because the blade can pass between two vertebrae to
      transect the cord. The neurologic injury that results is irreversible. The more
      common stab wounds, inflicted from behind, usually produce incomplete cord
      damage.

PMID- 11224895
TI  - Tension pneumothorax as a complication of video-assisted thorascopic surgery for
      anterior correction of idiopathic scoliosis in an adolescent female.
AB  - STUDY DESIGN: This case report illustrates the occurrence of intraoperative
      tension pneumothorax, a previously unreported complication occurring during
      anterior instrumentation for correction of scoliosis by video-assisted surgery.
      OBJECTIVES: To demonstrate a consequence of overadvancement of a Steinmann pin
      (guide wire). SUMMARY OF BACKGROUND DATA: Although intraoperative tension
      pneumothorax is admitted to be a theoretical complication of video-assisted
      surgery for anterior correction of idiopathic scoliosis, there has yet to be a
      case reported in the literature. This report presents the first case of this
      complication. METHODS: A 13-year-old girl who had right thoracic scoliosis with a
      curve measuring 54 degrees underwent video-assisted surgery discectomy and
      anterior spinal fusion with instrumentation of T5 through T11. Single-lung
      ventilation had been achieved with a double-lumen tube and the right lung was
      deflated. After approximately 4.5 hours of complication-free surgery,
      intraoperative fluoroscopy showed an approximately 2-cm overadvancement of a
      guide wire into the opposite hemithorax. Approximately 5 minutes after the
      overadvancement was corrected, the patient experienced a gradual increase in
      heart rate and a corresponding gradual decrease in oxygen saturation and both
      systolic and diastolic blood pressures. Approximately 35 minutes later, it was
      determined that the patient had sustained a tension pneumothorax of the left
      hemithorax. RESULTS: The patient underwent urgent partial reinflation of the
      right lung and a tube thoracostomy of the left thoracic cavity. Vital signs
      quickly returned to stable levels, and the left lung easily reinflated with the
      chest tube suction. The patient remained stable after the procedure was resumed
      (by right lung deflation). The remainder of the surgery and the postoperative
      course were uneventful. CONCLUSIONS: Although video-assisted surgery continues to
      gain popularity in the management of spinal deformities, the surgical team must
      be certain to pay meticulous attention to detail throughout the procedure. The
      early detection and treatment of complications can be life-preserving.

PMID- 11224896
TI  - Sacral cyst managed with cyst-subarachnoid shunt: a technical case report.
AB  - STUDY DESIGN: This report describes the cyst-subarachnoid shunt, a novel surgical
      treatment, for sacral cysts. OBJECTIVE: To introduce a new surgical technique for
      sacral cysts. SUMMARY OF BACKGROUND DATA: There is no consensus on the
      appropriate treatment for symptomatic sacral cysts. The hydrostatic and pulsatile
      forces of cerebrospinal fluid are attributed to the growth of the cyst and their
      becoming symptomatic. METHODS: The clinical and radiologic features of a 41-year
      old man with a symptomatic sacral cyst are detailed. A cyst-subarachnoid shunt
      was set to equalize the cerebrospinal fluid pressure between the cephalad thecal
      sac and the cyst. RESULTS: Immediately after surgery, the patient had no pain in
      his left leg and was free of pain at 2 years. Magnetic resonance imaging 1 year
      after surgery showed a decrease in the size of the cyst. CONCLUSION: Although
      this is a preliminary study, a cyst-subarachnoid shunt can be a useful
      alternative for symptomatic sacral cysts.

PMID- 11224897
TI  - Traumatic atlantoaxial distraction injury: a case report.
AB  - STUDY DESIGN: Case report. OBJECTIVES: Description of a rarely reported variant
      of traumatic C1-C2 dislocation and discussion of a favorable outcome in a
      nonsurgical treatment approach. SUMMARY OF BACKGROUND DATA: Atlantoaxial
      dislocation most commonly involves an anterior movement of C1 in relation to C2.
      Often, the integrity of the transverse ligament or odontoid process is
      compromised, and the atlantodental interval changed. The described patient
      sustained a purely craniocaudal atlantoaxial distractive lesion secondary to
      injury sustained in a high-speed motor vehicle accident. RESULTS: The initial
      treatment plan involved surgical stabilization subsequent to healing of a C1 ring
      fracture. After 12 weeks of external stabilization, ligamentous damage appeared
      well resolved. That there was no gross instability delayed using a surgical
      option. At periodic checkup, the patient was without symptoms. CONCLUSION: In
      this case, conservative management of a ligamentous C1-C2 injury was effective.
      At 5 years after trauma the patient was without sequelae. This outcome is in
      contrast to previous management of injuries of this type, all of which involved
      surgical intervention.

PMID- 11224898
TI  - The location of the pedicle and pars interarticularis in the axis.
AB  - STUDY DESIGN: This is an anatomic and radiologic study on the lateral mass of the
      C2 vertebra. OBJECTIVES: To define the location of the pedicle and pars
      interarticularis in the C2 vertebra. SUMMARY OF BACKGROUND DATA: Transpedicular
      screw fixation of the C2 has been addressed in the literature. However, the use
      of the anatomic terminology of the pedicle or pars interarticularis (isthmus) in
      C2 is confusing in most of orthopaedic and neurosurgical literature since C2 is
      considered a transitional vertebra. METHODS: Twenty dry C2 vertebrae were
      obtained for observation of the external anatomy of the C2 from superior,
      lateral, and inferior views. Six C2 vertebrae were harvested from cadavers and
      sectioned in the sagittal, horizontal, and coronal planes to observe the internal
      structures of the lateral mass using high resolution radiographs. RESULTS: Based
      on observation, the pedicle of the C2 vertebra is defined as the portion beneath
      the superior facet and anteromedial to the transverse foramen. The pars
      interarticularis or isthmus is defined as the narrower portion between the
      superior and inferior facets. No remarkable difference in bone density and
      trabecular bone orientation between the pedicle and pars interarticularis was
      noted. CONCLUSIONS: It is still more appropriate to call this procedure
      "transpedicular screw fixation" in the C2 to avoid confusion, although this
      technique requires placing a screw from the posterior aspect of the inferior
      articular process through the isthmus and pedicle into the vertebral body.

PMID- 11224899
TI  - The pathomechanism of spondylolytic spondylolisthesis in immature primate lumbar
      spines in vitro and finite element assessments.
AB  - STUDY DESIGN: Immature Chacma baboon (Papio ursinus) spine specimens were used to
      determine load-displacement behavior as related to disc injury. This was
      accomplished through the application of A-P shear force until failure of FSUs
      with pars defects. Several finite element models (FEMs) of the FSU were developed
      to study the mechanism of slippage in immature baboon lumbar spines. OBJECTIVES:
      The purpose was to show that spondylolisthesis (olisthesis) always occurs through
      the growth plate using a model similar to immature human lumbar spines. Using
      FEMs, the roles of facet orientation, pars interarticularis thickness, and a weak
      growth-plate in producing slippage were examined. SUMMARY OF BACKGROUND DATA:
      Progression from spondylolysis (lysis) to olisthesis occurs, most often, during
      the adolescent growth spurt. The biomechanical literature dealing with the
      slippage mechanism in the immature lumbar spine does not provide a clear
      understanding and is sparse. METHODS: Several groups of FSUs were subjected to A
      P shear force until failure. The results provided displacement at failure as a
      function of disc injury and flexion-extension fatigue. A bilateral pars defect
      was created in each specimen prior to application of A-P shear force using an MTS
      machine. Failure sites were assessed radiographically and histologically. A
      nonlinear 3-D FEM of the intact L4-L5 was created from CT scans. The model was
      modified to predict the effects of a pars fracture, a thin pars, a weak growth
      plate, and facet orientation on the shear load through the growth plate and
      stresses in the pars. RESULTS: Experimentally, failures always occurred through
      the growth-plate in the disc intact and disc-incised groups. In the intact FEM,
      the growth plate carried21% of the applied A-P shear force. The load increased
      when the facets were more sagittally oriented. The effect of thin pars and/or
      weaker growth plate was an increase in stresses in the pars. Changes in the load
      through the growth plate were minimal. CONCLUSIONS: The weakest link in immature
      baboon lumbar functional spinal units (FSUs) with lysis during an A-P shear load
      was the growth plate, between the cartilaginous and osseous end plates. Surgeons
      may assess this lesion on MRI views, thereby predicting the possible development
      and preventing progression of olisthesis. Finite element model results predict
      that more sagittally orientated facets and/or a pars fracture are prerequisites
      for olisthesis to occur.

PMID- 11224900
TI  - Acute respiratory compromise associated with flexed cervical traction after C2
      fractures.
AB  - STUDY DESIGN: Acute respiratory compromise is occasionally observed in a subgroup
      of patients with upper spinal injuries involving the C2 vertebrae. A
      retrospective review was performed to identify fracture types and risk factors
      for early respiratory deterioration following injury to the upper cervical spine.
      OBJECTIVES: To examine the frequency of respiratory complications encountered
      following traction manipulation of specific upper cervical spinal injuries
      involving the C2 vertebrae. SUMMARY OF BACKGROUND DATA: Major complications
      related to cervical skeletal traction are uncommon. Respiratory compromise with
      occasional mortality has been observed. Risk factors for acute respiratory
      failure are unknown. METHODS: The medical records of 166 consecutive patients
      with fractures of the C2 vertebrae admitted between January 1994 and July 1998 to
      a regional spinal cord injury center were examined. Demographic data, injury
      subtype, fracture displacement, respiratory status, treatment method, and outcome
      at discharge were examined. Patients with comorbidities compromising respiratory
      function were excluded. RESULTS: One hundred fifty-five patients met the
      inclusion criteria of this study. Sixty-one patients had Type II odontoid
      fractures of which 53 were displaced (32 posteriorly and 21 anteriorly). In
      addition, there were 21 patients with Type III odontoid fractures, 33 with axis
      C2 body fractures, 32 with Hangman's fractures, and eight patients with an os
      odontoideum. Thirteen of 32 patients with posteriorly displaced odontoid
      fractures experienced acute respiratory compromise following reduction with
      cervical skeletal traction and immobilization, while only three of the remaining
      123 patients had respiratory difficulties. Respiratory distress as a consequence
      of cervical spine fractures resulted in three deaths. Two of these patients had
      posteriorly displaced Type II odontoid fractures whose airway could not be
      emergently intubated. CONCLUSION: Frequent respiratory deterioration (40% of
      patients) during acute management of posteriorly displaced Type II odontoid
      fractures after reduction was observed. Physicians must be aware that cervical
      flexion in the treatment of posteriorly displaced odontoid fractures may
      significantly increase the risk of airway obstruction due to the presence of
      acute retropharyngeal swelling. This may be avoided with elective nasotracheal
      intubation in this upper cervical spine fracture subtype.

PMID- 11224901
TI  - Surface topography, Cobb angles, and cosmetic change in scoliosis.
AB  - STUDY DESIGN: Preliminary analysis of the clinical value of surface topography in
      a spinal deformity clinic. OBJECTIVES: The Cobb angle is the gold standard for
      the monitoring of scoliosis. This study was designed to determine whether surface
      topography would reflect Cobb angle status with sufficient reliability to permit
      its safe use as an alternative means of documentation in some circumstances.
      SUMMARY OF BACKGROUND DATA: Surface topography offers the possibility of
      describing spinal deformity more fully than radiographic measures alone. To be
      useful, it must ignore changes due to varying posture and reliably detect
      differences that are clinically significant, while broadening the ability to
      assess deformity. METHODS: Surface topography using Quantec () was obtained
      routinely in all patients attending a spinal deformity unit. Intrasubject
      variation was reduced by taking the mean for each parameter of four repositioned
      scans, which gives a smallest detectable change on all measures of approximately
      10 U. Fifty-nine patients with two sets of radiographs and topography scans were
      studied to determine the ability of the different measurements to detect
      significant change. RESULTS: There was a significant correlation between Cobb
      angle and Quantec spinal angle. A significant change in Cobb angle could be
      identified by associated change in at least one topographic measure in a
      significant proportion of cases. CONCLUSIONS: It is unlikely that topography will
      supplant radiography for the ascertainment of Cobb angles, because the error
      margins of both are wide, and the two are not measuring the same aspect of the
      deformity. The Quantec system is useful in patient monitoring as an alternative
      to radiography, without diminishing the standard of care.

PMID- 11224902
TI  - The efficacy of conservative treatment in patients with whiplash injury: a
      systematic review of clinical trials.
AB  - STUDY DESIGN: A systematic review of the literature. OBJECTIVES: To assess the
      efficacy of conservative treatment in patients with whiplash injuries. SUMMARY OF
      BACKGROUND DATA: Many treatments are available for patients with whiplash injury,
      but there continues to be no evidence for their accepted use. METHODS: A
      computerized literature search of Medline, Embase, Cinahl, Psychlit, and the
      Cochrane Controlled Trial Register was performed. Studies were selected if the
      design was a (randomized) clinical trial; if all patients had sustained a
      whiplash injury; if the type of intervention was a conservative one; if pain,
      global perceived effect, and participation in daily activities were used as one
      of the outcome measures, and if the publication was written in English, French,
      German, or Dutch. The methodologic quality was independently assessed by two
      reviewers by using the Maastricht-Amsterdam list. Three quality scores were
      calculated using this criteria list: the Overall Methodologic Quality Score, the
      Internal Validity Score, and the Delphi Quality Score. The conclusion of the
      review was based on articles that scored a quality score of at least 50% of the
      maximum available score on two of three quality scores. RESULTS: Eleven studies
      met the inclusion criteria. Only three studies satisfied at least 50% on two of
      three ways of calculating a quality score, indicating overall poor methodology.
      There was a high rank correlation among the three ways of calculating a quality
      score. No statistical pooling was performed because of the heterogeneity of the
      interventions. This review indicates that active treatments show a beneficial
      long-term effect on at least one of the primary outcome measures. CONCLUSION:
      Caution is needed when drawing a valid conclusion on the efficacy of conservative
      treatments in patients with whiplash injury. It appears that "rest makes rusty,"
      whereas active interventions have a tendency to be more effective in patients
      with whiplash injury.

PMID- 11224904
TI  - Hierarchical organization of the human auditory cortex revealed by functional
      magnetic resonance imaging.
AB  - The concept of hierarchical processing--that the sensory world is broken down
      into basic features later integrated into more complex stimulus preferences-
      originated from investigations of the visual cortex. Recent studies of the
      auditory cortex in nonhuman primates revealed a comparable architecture, in which
      core areas, receiving direct input from the thalamus, in turn, provide input to a
      surrounding belt. Here functional magnetic resonance imaging (fMRI) shows that
      the human auditory cortex displays a similar hierarchical organization: pure
      tones (PTs) activate primarily the core, whereas belt areas prefer complex
      sounds, such as narrow-band noise bursts.

PMID- 11224905
TI  - Role of familiar size in the control of grasping.
AB  - The present study examined whether the learned pictorial depth cue of "familiar
      size" could be used to plan a reaching and grasping movement in the absence of
      binocular vision. Sixteen right-handed subjects were presented with two different
      arrays, under monocular and binocular viewing conditions, in which a range of
      different "grasp-sized" spheres that were lit from within could be presented in
      an otherwise darkened environment. In the "familiar-size" presentation array,
      only one "standard" sized sphere was presented, which gave subjects an
      opportunity to learn the relationship between the standard sphere's retinal image
      size and its distance. In the "multiple" spheres presentation array, subjects
      could not learn such a relationship because on any one trial, one of four
      different sphere sizes could be present. In a second experiment, the effects of
      this paradigm on six subjects' perceptual reports of distance were examined by
      having subjects slide their index fingers apart along a horizontal rod to
      indicate the estimated distance of the spheres. When familiar size could not be
      used as a cue to distance, subjects produced more on-line corrections in their
      reaching and grasping movements to the standard-sized spheres--but only under
      monocular viewing conditions. It appears that subjects are able to exploit the
      learned relationship between an object's distance and its projected retinal image
      size to help program and control reaching and grasping movements when binocular
      vision is not available. Although the influence of familiar size on subjects'
      perceptual estimates is less clear, it is clear that subjects' perceptual
      estimates show poor absolute scaling for distance. This result further supports
      the notion that under normal viewing conditions the visuomotor system uses
      binocular information to program and control manual prehension, but is able to
      use pictorial information when binocular vision is denied.

PMID- 11224906
TI  - Similarity in perception: a window to brain organization.
AB  - This paper presents a neural model of similarity perception in identification
      tasks. It is based on self-organizing maps and population coding and is examined
      through five different identification experiments. Simulating an identification
      task, the neural model generates a confusion matrix that can be compared directly
      with that of human subjects. The model achieves a fairly accurate match with the
      pertaining experimental data both during training and thereafter. To achieve this
      fit, we find that the entire activity in the network should decline while
      learning the identification task, and that the population encoding of the
      specific stimuli should become sparse as the network organizes. Our results,
      thus, suggest that a self-organizing neural model employing population coding can
      account for identification processing while suggesting computational constraints
      on the underlying cortical networks.

PMID- 11224907
TI  - Failed suppression of direct visuomotor activation in Parkinson's disease.
AB  - The response times in choice-reaction tasks are faster when the relative spatial
      positions of stimulus and response match than when they do not match, even when
      the spatial relation is irrelevant to response choice. This spatial stimulus
      response (S--R) compatibility effect (i.e., the Simon effect) is attributed in
      part to the automatic activation of spatially corresponding responses, which need
      to be suppressed when the spatial location of stimulus and correct response do
      not correspond. The present study tested patients with Parkinson's disease and
      healthy control subjects in a spatial S--R compatibility task in order to
      investigate whether basal ganglia dysfunction in Parkinson's disease leads to
      disinhibition of direct visuomotor activation. High-density event-related brain
      potential recordings were used to chart the cortical activity accompanying
      attentional orientation and response selection. Response time measures
      demonstrated a failure to inhibit automatic response activation in Parkinson
      patients, which was revealed by taking into account a sequence-dependent
      modulation of the Simon effect. Event-related potential (ERP) recordings
      demonstrated that visuospatial orientation to target stimuli was accompanied by
      signal-locked activity above motor areas of the cortex, with similar latencies
      but an enhanced amplitude in patients compared to control subjects. The results
      suggest that inhibitory modulation of automatic, stimulus-driven, visuomotor
      activation occurs after the initial sensory activation of motor cortical areas.
      The failed inhibition in Parkinson's disease appears therefore related to a
      disturbance in processes that prevent early attention-related visuomotor
      activation, within motor areas, from actually evoking a response.

PMID- 11224908
TI  - Visual representation in the wild: how rhesus monkeys parse objects.
AB  - Visual object representation was studied in free-ranging rhesus monkeys. To
      facilitate comparison with humans, and to provide a new tool for
      neurophysiologists, we used a looking time procedure originally developed for
      studies of human infants. Monkeys' looking times were measured to displays with
      one or two distinct objects, separated or together, stationary or moving. Results
      indicate that rhesus monkeys used featural information to parse the displays into
      distinct objects, and they found events in which distinct objects moved together
      more novel or unnatural than events in which distinct objects moved separately.
      These findings show both commonalities and contrasts with those obtained from
      human infants. We discuss their implications for the development and neural
      mechanisms of higher-level vision.

PMID- 11224909
TI  - The role of large-scale memory organization in the mismatch negativity event
      related brain potential.
AB  - The mismatch negativity (MMN) component of event-related brain potentials is
      elicited by infrequent changes in regular acoustic sequences even if the
      participant is not actively listening to the sound sequence. Therefore, the MMN
      is assumed to result from a preattentive process in which an incoming sound is
      checked against the automatically detected regularities of the auditory sequence
      and is found to violate them. For example, presenting a discriminably different
      (deviant) sound within the sequence of a repetitive (standard) sound elicits the
      MMN. In the present article, we tested whether the memory organization of the
      auditory sequence can affect the preattentive change detection indexed by the
      MMN. In Experiment 1, trains of six standard tones were presented with a short,
      0.5-sec stimulus onset asynchrony (SOA) between tones in the train. This was
      followed by a variable SOA between the last standard and the deviant tone (the
      "irregular presentation" condition). Of 12 participants displaying an MMN at the
      0.5-sec predeviant SOA, it was elicited by 11 with the 2-sec predeviant SOA, in 5
      participants with the 7-sec SOA, and in none with the 10-sec SOA. In Experiment
      2, we repeated the 7-sec irregular predeviant SOA condition, along with a
      "regular presentation" condition in which the SOA between any two tones was 7
      sec. MMN was elicited in about half of the participants (9 out of 16) in the
      irregular presentation condition, whereas in the regular presentation condition,
      MMN was elicited in all participants. These results cannot be explained on the
      basis of memory-strength decay but can be interpreted in terms of automatic,
      auditory preperceptual grouping principles. In the irregular presentation
      condition, the close grouping of standards may cause them to become irrelevant to
      the mismatch process when the deviant tone is presented after a long silent
      break. Because the MMN indexes preattentive auditory processing, the present
      results provide evidence that large-scale preperceptual organization of auditory
      events occurs despite attention being directed away from the auditory stimuli.

PMID- 11224910
TI  - Functional magnetic resonance imaging of visual object construction and shape
      discrimination : relations among task, hemispheric lateralization, and gender.
AB  - We studied the brain activation patterns in two visual image processing tasks
      requiring judgements on object construction (FIT task) or object sameness (SAME
      task). Eight right-handed healthy human subjects (four women and four men)
      performed the two tasks in a randomized block design while 5-mm, multislice
      functional images of the whole brain were acquired using a 4-tesla system using
      blood oxygenation dependent (BOLD) activation. Pairs of objects were picked
      randomly from a set of 25 oriented fragments of a square and presented to the
      subjects approximately every 5 sec. In the FIT task, subjects had to indicate, by
      pushing one of two buttons, whether the two fragments could match to form a
      perfect square, whereas in the SAME task they had to decide whether they were the
      same or not. In a control task, preceding and following each of the two tasks
      above, a single square was presented at the same rate and subjects pushed any of
      the two keys at random. Functional activation maps were constructed based on a
      combination of conservative criteria. The areas with activated pixels were
      identified using Talairach coordinates and anatomical landmarks, and the number
      of activated pixels was determined for each area. Altogether, 379 pixels were
      activated. The counts of activated pixels did not differ significantly between
      the two tasks or between the two genders. However, there were significantly more
      activated pixels in the left (n = 218) than the right side of the brain (n =
      161). Of the 379 activated pixels, 371 were located in the cerebral cortex. The
      Talairach coordinates of these pixels were analyzed with respect to their overall
      distribution in the two tasks. These distributions differed significantly between
      the two tasks. With respect to individual dimensions, the two tasks differed
      significantly in the anterior--posterior and superior--inferior distributions but
      not in the left--right (including mediolateral, within the left or right side)
      distribution. Specifically, the FIT distribution was, overall, more anterior and
      inferior than that of the SAME task. A detailed analysis of the counts and
      spatial distributions of activated pixels was carried out for 15 brain areas (all
      in the cerebral cortex) in which a consistent activation (in > or = 3 subjects)
      was observed (n = 323 activated pixels). We found the following. Except for the
      inferior temporal gyrus, which was activated exclusively in the FIT task, all
      other areas showed activation in both tasks but to different extents. Based on
      the extent of activation, areas fell within two distinct groups (FIT or SAME)
      depending on which pixel count (i.e., FIT or SAME) was greater. The FIT group
      consisted of the following areas, in decreasing FIT/SAME order (brackets indicate
      ties): GTi, GTs, GC, GFi, GFd, [GTm, GF], GO. The SAME group consisted of the
      following areas, in decreasing SAME/FIT order : GOi, LPs, Sca, GPrC, GPoC, [GFs,
      GFm]. These results indicate that there are distributed, graded, and partially
      overlapping patterns of activation during performance of the two tasks. We
      attribute these overlapping patterns of activation to the engagement of partially
      shared processes. Activated pixels clustered to three types of clusters : FIT
      only (111 pixels), SAME-only (97 pixels), and FIT + SAME (115 pixels). Pixels
      contained in FIT-only and SAME-only clusters were distributed approximately
      equally between the left and right hemispheres, whereas pixels in the SAME + FIT
      clusters were located mostly in the left hemisphere. With respect to gender, the
      left-right distribution of activated pixels was very similar in women and men for
      the SAME-only and FIT + SAME clusters but differed for the FIT-only case in which
      there was a prominent left side preponderance for women, in contrast to a right
      side preponderance for men. We conclude that (a) cortical mechanisms common for
      processing visual object construction and discrimination involve mostly the left
      hemisphere, (b) cortical mechanisms specific for these tasks engage both
      hemispheres, and (c) in object construction only, men engage predominantly the
      right hemisphere whereas women show a left-hemisphere preponderance.

PMID- 11224911
TI  - The speed of sight.
AB  - Macaque monkeys were presented with continuous rapid serial visual presentation
      (RSVP) sequences of unrelated naturalistic images at rates of 14--222 msec/image,
      while neurons that responded selectively to complex patterns (e.g., faces) were
      recorded in temporal cortex. Stimulus selectivity was preserved for 65% of these
      neurons even at surprisingly fast presentation rates (14 msec/image or 72
      images/sec). Five human subjects were asked to detect or remember images under
      equivalent conditions. Their performance in both tasks was above chance at all
      rates (14--111 msec/image). The performance of single neurons was comparable to
      that of humans and responded in a similar way to changes in presentation rate.
      The implications for the role of temporal cortex cells in perception are
      discussed.

PMID- 11224912
TI  - A neural model of smooth pursuit control and motion perception by cortical area
      MST.
AB  - Smooth pursuit eye movements (SPEMs) are eye rotations that are used to maintain
      fixation on a moving target. Such rotations complicate the interpretation of the
      retinal image, because they nullify the retinal motion of the target, while
      generating retinal motion of stationary objects in the background. This poses a
      problem for the oculomotor system, which must track the stabilized target image
      while suppressing the optokinetic reflex, which would move the eye in the
      direction of the retinal background motion (opposite to the direction in which
      the target is moving). Similarly, the perceptual system must estimate the actual
      direction and speed of moving objects in spite of the confounding effects of the
      eye rotation. This paper proposes a neural model to account for the ability of
      primates to accomplish these tasks. The model simulates the neurophysiological
      properties of cell types found in the superior temporal sulcus of the macaque
      monkey, specifically the medial superior temporal (MST) region. These cells
      process signals related to target motion, background motion, and receive an
      efference copy of eye velocity during pursuit movements. The model focuses on the
      interactions between cells in the ventral and dorsal subdivisions of MST, which
      are hypothesized to process target velocity and background motion, respectively.
      The model explains how these signals can be combined to explain behavioral data
      about pursuit maintenance and perceptual data from human studies, including the
      Aubert--Fleischl phenomenon and the Filehne Illusion, thereby clarifying the
      functional significance of neurophysiological data about these MST cell
      properties. It is suggested that the connectivity used in the model may represent
      a general strategy used by the brain in analyzing the visual world.

PMID- 11224914
TI  - Differential impact of the FMR-1 full mutation on memory and attention
      functioning : a neuropsychological perspective.
AB  - Memory and attention processing were examined in a group of 15 adult Fragile-X
      syndrome (FXS) males with Fragile-X mental retardation 1 (FMR-1) full mutation
      and compared to two control groups: a learning disabled (LD) control and a normal
      functioning control. Performance was assessed across a wide range of tasks
      including working memory, recognition memory, selective attention, sustained
      attention, and attentional switching. All three groups performed at a comparable
      level on recognition memory tasks, and the Fragile-X males and LD control group
      performed worse than the control group on tasks of working memory and sustained
      attention. On a task of executive function, the Fragile-X males demonstrated a
      significant deficit in comparison to the LD control group and the normal control
      group, but performed better than the LD control group and at a comparable level
      to the control group on tasks of selective attention. Molecular analyses of the
      lymphocyte DNA provided little evidence for a correlation between expansion size
      and performance on tasks of memory and attention. The findings from the present
      study are discussed in the context of functional neuroimaging and brain-behavior
      molecular correlates.

PMID- 11224913
TI  - Behavioral and electrophysiological study of phonological priming between
      bisyllabic spoken words.
AB  - Phonological priming between bisyllabic (CV.CVC) spoken items was examined using
      both behavioral (reaction times, RTs) and electrophysiological (event-related
      potentials, ERPs) measures. Word and pseudoword targets were preceded by
      pseudoword primes. Different types of final phonological overlap between prime
      and target were compared. Critical pairs shared the last syllable, the rime or
      the coda, while unrelated pairs were used as controls. Participants performed a
      target shadowing task in Experiment 1 and a delayed lexical decision task in
      Experiment 2. RTs were measured in the first experiment and ERPs were recorded in
      the second experiment. The RT experiment was carried out under two presentation
      conditions. In Condition 1 both primes and targets were presented auditorily,
      while in Condition 2 the primes were presented visually and the targets
      auditorily. Priming effects were found in the unimodal condition only. RTs were
      fastest for syllable overlap, intermediate for rime overlap, and slowest for coda
      overlap and controls that did not differ from one another. ERPs were recorded
      under unimodal auditory presentation. ERP results showed that the amplitude of
      the auditory N400 component was smallest for syllable overlap, intermediate for
      rime overlap, and largest for coda overlap and controls that did not differ from
      one another. In both experiments, the priming effects were larger for word than
      for pseudoword targets. These results are best explained by the combined
      influences of nonlexical and lexical processes, and a comparison of the reported
      effects with those found in monosyllables suggests the involvement of rime and
      syllable representations.

PMID- 11224915
TI  - A developmental model for the evolution of artificial neural networks.
AB  - We present a model of decentralized growth and development for artificial neural
      networks (ANNs), inspired by developmental biology and the physiology of nervous
      systems. In this model, each individual artificial neuron is an autonomous unit
      whose behavior is determined only by the genetic information it harbors and local
      concentrations of substrates. The chemicals and substrates, in turn, are modeled
      by a simple artificial chemistry. While the system is designed to allow for the
      evolution of complex networks, we demonstrate the power of the artificial
      chemistry by analyzing engineered (handwritten) genomes that lead to the growth
      of simple networks with behaviors known from physiology. To evolve more complex
      structures, a Java-based, platform-independent, asynchronous, distributed genetic
      algorithm (GA) has been implemented that allows users to participate in
      evolutionary experiments via the World Wide Web.

PMID- 11224916
TI  - Pattern formation and optimization in army ant raids.
AB  - Army ant colonies display complex foraging raid patterns involving thousands of
      individuals communicating through chemical trails. In this article we explore, by
      means of a simple search algorithm, the properties of these trails in order to
      test the hypothesis that their structure reflects an optimized mechanism for
      exploring and exploiting food resources. The raid patterns of three army ant
      species, Eciton hamatum, Eciton burchelli, and Eciton rapax, are analyzed. The
      respective diets of these species involve large but rare, small but common, and a
      combination of large but rare and small but common food sources. Using a model
      proposed by Deneubourg et al. [4], we simulate the formation of raid patterns in
      response to different food distributions. Our results indicate that the
      empirically observed raid patterns maximize return on investment, that is, the
      amount of food brought back to the nest per unit of energy expended, for each of
      the diets. Moreover, the values of the parameters that characterize the three
      optimal pattern-generating mechanisms are strikingly similar. Therefore the same
      behavioral rules at the individual level can produce optimal colony-level
      patterns. The evolutionary implications of these findings are discussed.

PMID- 11224917
TI  - On meme--gene coevolution.
AB  - In this article we examine the effects of the emergence of a new replicator,
      memes, on the evolution of a pre-existing replicator, genes. Using a version of
      the NKCS model we examine the effects of increasing the rate of meme evolution in
      relation to the rate of gene evolution, for various degrees of interdependence
      between the two replicators. That is, the effects of memes' (suggested) more
      rapid rate of evolution in comparison to that of genes is investigated using a
      tunable model of coevolution. It is found that, for almost any degree of
      interdependence between the two replicators, as the rate of meme evolution
      increases, a phase transition-like dynamic occurs under which memes have a
      significantly detrimental effect on the evolution of genes, quickly resulting in
      the cessation of effective gene evolution. Conversely, the memes experience a
      sharp increase in benefit from increasing their rate of evolution. We then
      examine the effects of enabling genes to reduce the percentage of gene
      detrimental evolutionary steps taken by memes. Here a critical region emerges as
      the comparative rate of meme evolution increases, such that if genes cannot
      effectively select memes a high percentage of the time, they suffer from meme
      evolution as if they had almost no selective capability.

PMID- 11224918
TI  - Talking helps: evolving communicating agents for the predator-prey pursuit
      problem.
AB  - We analyze a general model of multi-agent communication in which all agents
      communicate simultaneously to a message board. A genetic algorithm is used to
      evolve multi-agent languages for the predator agents in a version of the predator
      prey pursuit problem. We show that the resulting behavior of the communicating
      multi-agent system is equivalent to that of a Mealy finite state machine whose
      states are determined by the agents' usage of the evolved language. Simulations
      show that the evolution of a communication language improves the performance of
      the predators. Increasing the language size (and thus increasing the number of
      possible states in the Mealy machine) improves the performance even further.
      Furthermore, the evolved communicating predators perform significantly better
      than all previous work on similar prey. We introduce a method for incrementally
      increasing the language size, which results in an effective coarse-to-fine search
      that significantly reduces the evolution time required to find a solution. We
      present some observations on the effects of language size, experimental setup,
      and prey difficulty on the evolved Mealy machines. In particular, we observe that
      the start state is often revisited, and incrementally increasing the language
      size results in smaller Mealy machines. Finally, a simple rule is derived that
      provides a pessimistic estimate on the minimum language size that should be used
      for any multi-agent problem.

PMID- 11224919
TI  - Cardiovascular physiology during fetal development and implications for tissue
      engineering.
AB  - Shear stress in fluid dynamics has a well-known impact on vascular cell
      morphology, proliferation, orientation, and the organization and composition of
      extracellular matrix. There is an increasing interest in the field of tissue
      engineering to use defined shear stress in bioreactors for tissue conditioning
      and guided tissue formation. Especially for cardiovascular structures like heart
      valves or blood vessels, the type and appropriate amount of shear stress needed
      to improve tissue formation remains speculative. The authors believe that fetal
      like conditions may be more optimal for new tissue formation in a bioreactor. The
      purpose of this review is to delineate parameters of cardiovascular physiology
      during embryonic and fetal development that may have a potential impact on the
      design and setting of bioreactors for cardiovascular tissue engineering.

PMID- 11224920
TI  - Development and characterization of tissue-engineered aortic valves.
AB  - Tissue-engineered aortic valves, known as recellularized heart valves, were
      developed by seeding human neonatal fibroblasts onto decellularized, porcine
      aortic valves. Recellularized heart valves were cultured up to 8 weeks in a novel
      bioreactor that imposed dynamic pulsatile fluid flow to expose the dermal
      fibroblasts to mechanical forces. Our data showed that, under static or dynamic
      flow conditions, dermal fibroblasts attached to and migrated into the
      decellularized, porcine valve scaffolding. The human cells remained viable as
      indicated by MTT viability staining. Gradual colonization of the decellularized
      porcine scaffolding by the human dermal fibroblasts was shown histologically by
      hematoxylin & eosin staining, immunocytochemically using a monoclonal antibody
      directed against prolyl-4-hydroxylase (an intracellular enzyme expressed by human
      fibroblasts synthesizing collagen), and quantitative digital image analyses.
      Thymidine and proline radiolabeled analog studies at 1, 2 and 4 weeks of
      individual leaflets cultured statically demonstrated that the human fibroblasts
      were mitotic and synthesized human extracellular matrix proteins, thereby
      supplementing the existing porcine matrix. The overall approach results in a
      heart valve populated with viable human cells. In the development of valves that
      perform in a similar manner as natural biological structures, this approach may
      present some unique benefits over current medical therapies.

PMID- 11224921
TI  - Biodegradable polymer scaffolds with well-defined interconnected spherical pore
      network.
AB  - Scaffolding plays pivotal role in tissue engineering. In this work, a novel
      processing technique has been developed to create three-dimensional biodegradable
      polymer scaffolds with well-controlled interconnected spherical pores. Paraffin
      spheres were fabricated with a dispersion method, and were bonded together
      through a heat treatment to form a three-dimensional assembly in a mold.
      Biodegradable polymers such as PLLA and PLGA were dissolved in a solvent and cast
      onto the paraffin sphere assembly. After dissolving the paraffin, a porous
      polymer scaffold was formed. The fabrication parameters were studied in relation
      to the pore shape, interpore connectivity, pore wall morphology, and mechanical
      properties of the polymer scaffolds. The compressive modulus of the scaffolds
      decreased with increasing porosity. Longer heat treatment time of the paraffin
      spheres resulted in larger openings between the pores of the scaffolds. Foams of
      smaller pore size (100-200 microm) resulted in significantly lower compressive
      modulus than that of larger pore sizes (250-350 or 420-500 microm). The PLLA
      foams had a skeletal structure consisting of small platelets, whereas PLGA foams
      had homogeneous skeletal structure. The new processing technique can tailor the
      polymer scaffolds for a variety of potential tissue engineering applications
      because of the well-controlled architecture, interpore connectivity, and
      mechanical properties.

PMID- 11224922
TI  - The effect of zinc-crystallized glucagon-like peptide-1 on insulin secretion of
      macroencapsulated pancreatic islets.
AB  - This research investigates the use of an insulinotropic factor, glucagon-like
      peptide-1 (GLP-1), to enhance insulin secretion from islets within a
      macrocapsule. A zinc-crystallized form of GLP-1 was added to the macrocapsule
      device to have a longer and more controlled release of the bioactive monomer GLP
      1. The type of macrocapsule device used for this study consisted of a hollow
      fiber (MWCO 100,000 and 1 mm inner diameter) containing rat islets and GLP-1
      crystals within a poly(N-isopropylacrylamide-co-acrylic acid) (2 mol% acrylic
      acid) matrix. When incubating the system in media with a high glucose
      concentration (300 mg/dL), insulin secretion was enhanced with a >85% increase
      after an induction period. When the same type of system was used in a dynamic
      perfusion experiment, similar results were obtained. GLP-1 crystals can be an
      effective form to be entrapped in a bioartificial pancreas to enhance insulin
      secretion function, especially at high glucose concentrations.

PMID- 11224923
TI  - Fibrin glue as matrix for cultured autologous urothelial cells in urethral
      reconstruction.
AB  - In the present study, we have established a technique to create an artificial
      urethra in a rat animal model by transplantation of in vitro-expanded urothelial
      cells onto an in vivo-prefabricated tube formation using tissue engineering
      methods. Urothelial cells from isogenic rats were harvested for culture. A
      silicon catheter was used to induce a connective tissue capsule-tube formation
      underneath the abdominal skin. Two weeks later, the cultivated urothelial cells
      were seeded onto the lumen of this tube using fibrin glue as delivery matrix. The
      histomorphological and immunohistochemical studies revealed a viable multilayered
      urothelium, lining the inner surface of the prior formed connective tissue tube
      formation 4 weeks after grafting the cells. We have shown that cultured and in
      vitro-expanded urothelial cells can be successfully reimplanted onto a
      prefabricated tube-like structure using fibrin glue as a delivery matrix and
      native cell expansion vehicle. The results suggest that the creation of an
      artificial urethra may be achieved in vivo using tissue engineering methods,
      showing potential for urethral reconstruction and providing autologous urothelium
      for reconstructive surgery in the genitourinary tract.

PMID- 11224924
TI  - Evaluation of metallic and polymeric biomaterial surface energy and surface
      roughness characteristics for directed cell adhesion.
AB  - Directed cell adhesion remains an important goal of implant and tissue
      engineering technology. In this study, surface energy and surface roughness were
      investigated to ascertain which of these properties show more overall influence
      on biomaterial-cell adhesion and colonization. Jet impingement was used to
      quantify cellular adhesion strength. Cellular proliferation and extracellular
      matrix secretion were used to characterize colonization of 3T3MC fibroblasts on:
      HS25 (a cobalt based implant alloy, ASTM F75), 316L stainless steel, Ti-6Al4V (a
      titanium implant alloy), commercially pure tantalum (Ta), polytetrafluoroethylene
      (PTFE), silicone rubber (SR), and high-density polyethylene (HDPE). The metals
      exhibited a nearly five-fold greater adhesion strength than the polymeric
      materials tested. Generally, surface energy was proportional to cellular adhesion
      strength. Only polymeric materials demonstrated significant increased adhesion
      strength associated with increased surface roughness. Cellular adhesion on metals
      demonstrated a linear correlation with surface energy. Less than half as much
      cellular proliferation was detected on polymeric materials compared to the
      metals. However the polymers tested demonstrated greater than twice the amount of
      secreted extracellular matrix (ECM) proteins on a per cell basis than the
      metallic materials. Thus, surface energy may be a more important determinant of
      cell adhesion and proliferation, and may be more useful than surface roughness
      for directing cell adhesion and cell colonization onto engineered tissue
      scaffoldings.

PMID- 11224925
TI  - Stimulating effect of an arteriovenous shunt on the in vivo growth of isografted
      fibroblasts: a preliminary report.
AB  - Isogenous fibroblasts derived from the skin of inbred Sprague-Dawley rats were
      cultured in vitro, labeled with bisbenzamide (BB) or carboxyfluorescein diacetate
      (CFDA), and seeded into polycarbonate growth chambers. After 24 h incubation in
      vitro, the chambers, either empty or containing an arteriovenous (AV) shunt, were
      implanted subcutaneously into the inguinal region of Sprague-Dawley rats and
      examined by fluorescence microscopy 2 or 7 days later. The AV shunt remained
      patent in all experiments. The density of labeled cells on the chamber surface in
      all chambers decreased in the first 2 days after insertion. At 7 days, the cell
      density in the empty chambers had not altered from the 2-day level, but the
      density in the AV shunt containing chambers had increased to almost three times
      the day 2 level (p = 0.013). It appears that an AV shunt can induce a significant
      proliferation of fibroblasts implanted adjacent to it. For at least 7 days after
      labeling, BB and CFDA provide a simple and effective method of quantitative
      detection of implanted fibroblasts. It is concluded that nutrients from the AV
      shunt implanted in a growth chamber result in a significant increase in the
      number of viable, matrix-synthesizing cells, compared with AV shunt-free
      controls.

PMID- 11224926
TI  - The effect of fibroblast growth factor and transforming growth factor-beta on
      porcine chondrocytes and tissue-engineered autologous elastic cartilage.
AB  - Elastic cartilage responds mitogenically in vitro to transforming growth factor
      beta (TGF-beta) and basic fibroblast growth factor (basic FGF). We studied the
      effects of these growth factors separately or in a combination on porcine
      auricular chondrocytes in vitro and on the autologous elastic cartilage produced.
      Cells were harvested from the elastic auricular cartilage of 16- to 18-kg
      Yorkshire swine. Viability and quantification of the cells was determined. Cells
      were plated at equal concentration and studied in vitro in one of four identical
      media environments except for the growth factors: Group I contained Ham's F-12
      with supplements but no growth factors, Group II also contained basic-FGF, Group
      III also contained TGF-beta, and Group IV also contained a combination of both
      growth factors. After 3 weeks in vitro, the cells were chemically dissociated
      with 0.25% trypsin. Cell suspensions composed of 3 x 10(7) cells/cc in 30%
      Pluronic F-127/Ham's F-12 were injected subcutaneously. Implants were harvested
      at 6, 8, 10, and 12 weeks of in vivo culture and then were examined with
      histologic stains. After 3 weeks of in vitro culture the total number of cells
      was as follows: Group I, 1.8 x 10(8); Group II, 3.5 x 10(8); Group III, 1.3 x
      10(8); Group IV, 2.5 x 10(8). After 8 weeks of in vivo autologous implantation,
      the average weight (g) and volume (cm3) of each group was as follows: Group I,
      0.7 g/0.15 cm3; Group II, 1.5 g/0.8 cm3; Group III, 0.6 g/0.1 cm3; Group IV, 1.2
      g/0.3 cm3. Histologically, Groups I, II, and IV generated cartilage similar to
      native elastic cartilage, but Group III specimens demonstrated fibrous tissue
      ingrowth. Basic FGF produced the most positive enhancement on the quantity and
      quality of autologous tissue engineered elastic cartilage produced in this
      porcine model both in vitro and in vivo.

PMID- 11224927
TI  - Differentiation of osteoblasts and in vitro bone formation from murine embryonic
      stem cells.
AB  - Pluripotent embryonic stem (ES) cells have the potential to differentiate to all
      fetal and adult cell types and might represent a useful cell source for tissue
      engineering and repair. Here we show that differentiation of ES cells toward the
      osteoblast lineage can be enhanced by supplementing serum-containing media with
      ascorbic acid, beta-glycerophosphate, and/or dexamethasone/retinoic acid or by co
      culture with fetal murine osteoblasts. ES cell differentiation into osteoblasts
      was characterized by the formation of discrete mineralized bone nodules that
      consisted of 50-100 cells within an extracellular matrix of collagen-1 and
      osteocalcin. Dexamethasone in combination with ascorbic acid and beta
      glycerophosphate induced the greatest number of bone nodules and was dependent on
      time of stimulation with a sevenfold increase when added to ES cultures after,
      but not before, 14 days. Co-culture with fetal osteoblasts also provided a potent
      stimulus for osteogenic differentiation inducing a fivefold increase in nodule
      number relative to ES cells cultured alone. These data demonstrate the
      application of a quantitative assay for the derivation of osteoblast lineage
      progenitors from pluripotent ES cells. This could be applied to obtain purified
      osteoblasts to analyze mechanisms of osteogenesis and for use of ES cells in
      skeletal tissue repair.

PMID- 11224928
TI  - Some recent developments in U.S. patent law.

PMID- 11224929
TI  - Alcohol use can result in enhanced drug metabolism in HIV pharmacotherapy.

PMID- 11224930
TI  - Follow-up of vertically HIV-1-infected long-surviving children.
AB  - This study describes the clinical, immunologic, and virological characteristics
      of 30 vertically human immunodeficiency virus type 1 (HIV-1)-infected children
      older than 8 years of age (long-survivors) before the introduction of protease
      inhibitors therapy. All of them were followed from birth. At the age of 8 years,
      7 children presented no HIV-1-associated signs or only mild ones and only 5 had
      severe clinical manifestations (acquired immune deficiency virus [AIDS]). The
      remaining 18 children presented moderate signs with some immunodeficiency. The
      follow-up from 8 years of age (3.5 years on the average) showed that 6 children
      remained asymptomatic and were therefore defined as long-survivors nonprogressors
      (average, 13 years) and only 4 children developed AIDS. Progressive
      encephalopathy was the most striking clinical manifestation at follow-up and
      occurred in 6 children (always after immunodeficiency) with a polymorphic picture
      combining eye movement alterations, pyramidal signs and symptoms and mental
      deterioration. The majority of our long-survivors carried a virus with
      nonsyncytia-inducing phenotype, thus confirming its association with long
      survival. A switch to syncytia-inducing phenotype was observed only in 2 cases
      during the follow-up, but their clinical status did not change at follow-up.

PMID- 11224931
TI  - The evolving mode of presentation of HIV-infected patients to health services of
      northern Spain: 1985 through December 1999.
AB  - To evaluate the mode in which human immunodeficiency virus (HIV)-infected
      patients have had their first contact with the health services throughout time as
      well as their demographic and immunologic features, all 1,076 adult HIV-infected
      patients seen at our institution were grouped by the year of presentation. The
      patients' age and gender, the mode of presentation (admitted through the
      emergency department or seen at the outpatient clinic), and the presence of
      acquired immune deficiency syndrome (AIDS)-defining conditions and CD4 counts at
      the time of presentation were analyzed. The patients' age at presentation and the
      rate of female patients increased throughout time (p < 0.001, and p = 0.01,
      respectively). There was a progressive decline in the proportion of patients who
      were hospitalized until the mid-1990s (p < 0.0001), followed by a rise during the
      subsequent years (p = 0.04). This U-shaped curve was opposite to that of CD4
      counts, which was ascending until 1994 (p = 0.04), to decline progressively later
      (p = 0.1). Patients whose first contact with the hospital was through admission
      had lower CD4 counts (p = 0.007), and higher rates of AIDS diagnosis throughout
      time (p < 0.0001). We conclude that some features of HIV-infected patients at the
      time of their first contact with the health services are changing over time, such
      as older age, increasing numbers of women, and higher degrees of
      immunosuppression. These findings seem to reflect the increasing number of
      patients unaware of their past risk factors, and should be considered for the
      development of strategies targeted to this population in order to allow earlier
      detection of their infection.

PMID- 11224932
TI  - STD screening among HIV-infected patients in care, San Francisco.
AB  - The Centers for Disease Control and Prevention recommends sexually transmitted
      disease (STD) screening among human immunodeficiency virus (HIV)-infected persons
      as a means of HIV prevention. HIV-infected persons in care may be an important
      target group in which to conduct regular STD screening to prevent enhanced
      transmission of HIV. We conducted STD screening for syphilis and two causes of
      urethritis, chlamydia, and gonorrhea, among 447 HIV-infected persons at two busy,
      urban clinics in San Francisco: a general HIV acquired immune deficiency syndrome
      (AIDS) care clinic and a methadone maintenance clinic. There were no new cases of
      syphilis identified and only two prevalent cases of chlamydia. While STD
      screening was feasible and acceptable in this population, the benefits of
      screening for asymptomatic gonococcal and chlamydial infection remain to be
      determined. Because these two pathogens only cause about 20% of urethritis,
      broader screening tests for urethritis, e.g., leukocyte esterase or urine
      microscopy, may be more useful. Finally, this study reaffirms the notion that
      local data should be used to evaluate national screening recommendations.

PMID- 11224933
TI  - Disclosure of HIV status: cultural issues of Asian patients.
AB  - Disclosure of human immunodeficiency virus (HIV) status is a difficult emotional
      task creating opportunities for both support and rejection. For Asian patients
      there may be additional self-imposed barriers to disclosure that are rooted in
      cultural values. The purpose of this article is to describe how Asian cultural
      values of harmony and avoidance of conflict affect the disclosure experiences of
      HIV-positive Asian American and immigrants. Effective practice guidelines have
      been developed based on this information. Based on in-depth interviews with 16
      HIV-positive Asian men, three focal issues were identified that serve as barriers
      to disclosure to family members: protection of family from shame, protection of
      family from obligation to help, and avoidance of communication regarding highly
      personal information. Additionally, patients felt disclosure was inhibited by the
      lack of HIV education to which families living overseas may have access. This is
      compounded by their lack of access to translated materials that they could send
      to family members. Similar to past disclosure research with non-Asian samples,
      the findings suggest that gay Asian men seek emotional support from gay friends.
      They would consider disclosing to relatives only when health reasons necessitated
      it. It is essential that helping professionals be attentive to the dishonor that
      patients may experience through disclosure and the stigma associated with being
      gay. Patients who are considering making a disclosure may need assistance with
      thinking through ways to provide HIV/acquired immune deficiency syndrome (AIDS)
      education to those family members that have little knowledge in this area. This
      may include translating or locating informational brochures translated into the
      family's language.

PMID- 11224934
TI  - Concerns of pregnant women about bing tested for HIV: a study in a predominately
      Mexican-American population.
AB  - More than 90% of pediatric acquired immune deficiency syndrome (AIDS) cases are
      due to mother-to-child (vertical) transmission. Medical intervention can reduce
      the risk of vertical transmission human immunodeficiency virus (HIV) from 25% to
      less than 8%. However, studies have suggested that approximately one-fourth of
      women may refuse HIV testing as part of routine prenatal care. The purpose of
      this study was to identify concerns that pregnant women might have that would
      impact their decision to undergo HIV testing in pregnancy. The study is a cross
      sectional survey of 413 pregnant women in south Texas. A survey questionnaire was
      used to assess reasons why subjects might avoid HIV testing and to assess their
      risks for HIV infection. The reasons for not wanting HIV testing grouped around
      four themes: (1) fear of being stigmatized as sexually promiscuous or as an
      injecting drug user; (2) denial about the possibility of being infected; (3)
      fatalism; and (4) of rejection leading to loss of emotional and financial
      support. Overall, 15% of subjects who had not been previously tested (5% of all
      subjects) indicated that they would refuse HIV testing, a rate which is below
      rates of 20%-24% in previous studies. The lower rate of refusal for HIV testing
      in our study may reflect a downward trend nationally in the rate of refusal for
      prenatal testing. Many women have concerns about HIV testing, although these
      concerns may not necessarily prevent them from undergoing testing. Physicians and
      policy makers need to be aware of women's concerns and fears when implementing
      HIV testing policies.

PMID- 11224935
TI  - Multidimensional aspects of pain in HIV-infected individuals.
AB  - To study the prevalence, intensity, and quality of pain in patients with human
      immunodeficiency virus (HIV) infection and to evaluate factors influencing the
      different components of pain, a self-administered multidimensional pain
      questionnaire (Italian Pain Questionnaire [IPQ]) was administered to 153 HIV
      patients admitted to the Department of Infectious Diseases of a teaching hospital
      over a 7-month period. Ninety-three (60.8%) patients experienced pain for a total
      of 131 pain sites. The intensity and the nonsensorial components of pain were
      greater in ward patients compared to outpatients. In 70% of pain syndromes it was
      not possible to define the etiology at the time of the visit. Pain was observed
      more frequently in intravenous drug users (IDUs) (72.9%) compared to patients
      with other HIV modalities of transmission (50.6%) (p = 0.008). The mean value of
      sensory class was greater in patients who were not IDUs. Within IDUs group there
      was a predominance of descriptors of the affective class over the sensory class.
      The prevalence of pain is high in HIV-infected individuals. The different
      components of pain are influenced by the modality of transmission and the setting
      of care. The assessment of scores of different components of pain could help to
      select and monitor appropriate interventions in pain control.

PMID- 11224936
TI  - Revised nevirapine insert.

PMID- 11224937
TI  - Younger teens and oral sex.

PMID- 11224939
TI  - The role of diet in disease prevention.

PMID- 11224940
TI  - CDC Urban Research Centers: community-based participatory research to improve the
      health of urban communities.

PMID- 11224941
TI  - Toward optimal health: the experts discuss heart disease in women. Interview by
      Jodi Godfrey Meisler.

PMID- 11224942
TI  - Development and implementation of novel community outreach methods in women's
      health issues: the National Centers of Excellence in Women's Health.
AB  - Numerous outreach efforts have been employed to educate both lay and professional
      communities about many medical issues. As part of our contracts with the Public
      Health Service, Office of Women's Health, Department of Health and Human
      Services, the National Centers of Excellence (CoEs) in Women's Health have been
      charged with creating innovative and effective methods of educating these
      audiences about the major issues involved in women's health. This mission is
      particularly critical in the arena of women's health, as women are responsible
      for approximately 75% of the healthcare decisions made by and for American
      families, and past efforts to provide them with good, evidence-based information
      have been fraught with difficulties ranging from financial to cultural. We report
      herein some of our successful novel outreach efforts. A common thread throughout
      this account is that among the most successful of the outreach activities are
      those that involve or incorporate existing community groups committed to women's
      health.

PMID- 11224944
TI  - Information technology and the National Centers of Excellence in Women's Health.
AB  - Women are increasingly turning to the Internet for health information. The
      National Centers of Excellence in Women's Health (U.S. Dept. of Health and Human
      Services) have as one goal the use of information technology to improve care of
      women. Telemedicine, the Internet, and Resource Centers were used for patient
      consultation, patient support, support of women in academics, and clinician
      education regarding women's health. Access of the lay public to high-quality
      health information was achieved using the Internet as well as Resource Centers
      employing Internet educational modalities. Telemedicine, distance learning for
      clinicians and patient consultations for those far from medical care, has been
      used successfully. For clinicians, continuing medical education regarding women's
      health and calendars of opportunities for education in women's health were made
      available on-line. Creative new uses of information technology have been
      developed by the Centers of Excellence in Women's Health. These modalities may be
      adopted, tested, and adapted by others seeking to improve the care and health of
      women.

PMID- 11224943
TI  - Using women's health research to develop women leaders in academic health
      sciences: the National Centers of Excellence in Women's Health.
AB  - While the number of women entering U.S. medical schools has risen substantially
      in the past 25 years, the number of women in leadership positions in academic
      medicine is disproportionately small. The traditional pathway to academic
      leadership is through research. Women's health research is an ideal venue to fill
      the pipeline with talented women physicians and scientists who may become
      academic leaders in positions where they can promote positive change in women's
      health as well as mentor other women. The Office on Women's Health (OWH) in the
      U.S. Department of Health and Human Services has contracted with 18 academic
      medical centers to develop National Centers of Excellence in Women's Health.
      Emphasizing the integral link between women's health and women leaders, each of
      the Centers of Excellence must develop a leadership plan for women in academic
      medicine as part of the contract requirements. This paper describes the training
      programs in women's health research that have developed at five of the academic
      medical centers: the University of Wisconsin, Magee Women's Hospital, the
      University of Maryland, Medical College of Pennsylvania Hahnemann University, and
      the University of Illinois at Chicago. We discuss some of the challenges faced
      for both initiation and future viability of these programs as well as criteria by
      which these programs will be evaluated for success.

PMID- 11224945
TI  - Modifiable and nonmodifiable factors associated with osteoporosis in
      postmenopausal women: results from the Third National Health and Nutrition
      Examination Survey, 1988-1994.
AB  - We wished to study the relationship between modifiable and nonmodifiable factors
      that were correlated with osteoporosis using a national sample of women aged 50
      years and older who have never been on hormone replacement therapy (HRT). We used
      a cross-sectional study design with a nationally representative sample with a
      detailed clinical examination and a home interview. Between 1988 and 1994, 1953
      postmenopausal women who had never been on HRT, aged 50 years and older, were
      examined as part of the Third National Health and Nutrition Examination Survey
      (NHANES III). Mexican Americans and non-Hispanic blacks were oversampled to
      produce reliable estimates for these groups. Bone density measurements of four
      proximal femur sites were assessed by using x-ray absorptiometry (DEXA). A DEXA
      measurement at any single femur site indicated osteoporosis if it was >2.5
      standard deviations (SD) below the reference mean of 20--29-year-old women. The
      study demonstrated that numerous factors, both modifiable and nonmodifiable, were
      significantly related to the prevalence of osteoporosis. The modifiable factors
      identified were participation in physical activity (three to five times per week)
      and body mass index (BMI). Nonmodifiable factors included age, race, and mother's
      history. With the aging population, osteoporosis is a growing concern for the
      medical community. It is suggested that educational strategies are needed to
      increase awareness of factors that contribute to maintaining bone health among
      postmenopausal women. Emphasis may be placed on maintaining regular physical
      activity.

PMID- 11224947
TI  - Recruitment and retention of healthy minority women into community-based
      longitudinal research.
AB  - This report examines the impact of individualized, population-based recruitment
      and retention approaches on the development of a subject pool, enrollment, and
      retention at 12 months of healthy, community-based women in three ethnic groups:
      African Americans, non-Hispanic European Americans, and Mexicans/Central
      Americans. Of 722 women contacted and screened, 346 (48%) were eligible and
      consented to participate. Attrition at 12 months was low (10%) compared with
      other published reports. The largest group of potential subjects was identified
      through broadcast media approaches, but this method produced the highest number
      of ineligible women and highest rate of attrition. Printed matter produced the
      next largest group of potential subjects, but ineligibility was high (53%). Face
      to-face interactions enrolled the highest proportion of eligible women (84%) and
      lowest overall attrition (7%). Direct referral yielded fairly efficient
      enrollments (57%) and average attrition. Multiple approaches for recruitment can
      produce a diverse sample of healthy, community-based women. Face-to-face
      recruitment results in the highest yield of participants with the lowest
      attribution but is presumed to require more resources.

PMID- 11224948
TI  - Tips for successful surfing.

PMID- 11224946
TI  - Hot flashes in the late reproductive years: risk factors for Africa American and
      Caucasian women.
AB  - Hot flashes are a primary reason that midlife women seek medical care, but there
      is little information about the onset or the predictors of hot flashes in the
      years before the menopause. This study examines women's experience of hot flashes
      in the late reproductive years, comparing African American and Caucasian women,
      and identifies hormonal, behavioral, and environmental risk factors for hot
      flashes associated with ovarian aging. Data are from a population-based
      prospective cohort study of ovarian aging in women who were ages 35--47, in
      general good health, and had regular menstrual cycles at study enrollment. Hot
      flashes were assessed by subject report in a structured interview at the first
      follow-up period and correlated highly with previous prospective daily ratings of
      hot flashes (p = 0.0001). Blood samples were obtained in the first 6 days of the
      menstrual cycle in two consecutive cycles at enrollment and two consecutive
      cycles at follow-up. Predictor variables include hormone measures, structured
      interview, and standard questionnaire data. Thirty-one percent of the sample (n =
      375) reported hot flashes (mean age 41 years). In bivariate analysis, more
      African American than Caucasian women reported hot flashes (38% vs. 25%, p =
      0.01). Significant predictors of hot flashes in the final multivariable logistic
      regression model were higher follicle-stimulating hormone (FSH) levels (odds
      ratio [OR] 3.19), anxiety (OR 1.06), baseline menopausal symptoms (OR 4.91),
      alcohol use (OR 1.09), body mass index (BMI) (OR 1.04), and parity (OR 1.20).
      Race did not predict hot flashes after adjusting for these variables. Hot flashes
      commonly occur before observable menstrual irregularities in the perimenopause
      and are associated with both hormonal and behavioral factors. The association of
      hot flashes with increased body mass (BMI) challenges the current "thin"
      hypothesis and raises important questions about the role of BMI in hormone
      dynamics in the late reproductive years.

PMID- 11224950
TI  - Relapse prevention strategies and techniques with erectile dysfunction.
AB  - The crucial issues in relapse prevention are building erectile comfort and
      confidence and maintaining positive, realistic expectations. The basis of relapse
      prevention is comprehensive, high-quality sex therapy. Erectile dysfunction is
      best conceptualized as a couple issue with the focus on establishing a broad
      based, flexible couple style that integrates intimacy, pleasuring and eroticism.
      Specific strategies are proposed for men who use Viagra.

PMID- 11224951
TI  - A comparison of subjective and physiological measures of mechanically produced
      and erotically produced erections (or, is an erection an erection?).
AB  - The current investigation explores possible reasons for the poor overall success
      rates of medical techniques used in the treatment of erectile dysfunction. This
      is the first study to compare directly the psychological impact of a mechanically
      produced versus an erotically produced erection. Subjective and objective
      parameters of sexual arousal were used to compare the experience of a
      mechanically attained erection versus an erotically stimulated erection. Twenty
      eight (28) men without sexual dysfunction were asked to reach a full erection
      during each of the following two conditions: (a) by using an ErecAid System and
      (b) by self-stimulating while watching an erotic video. The results of this study
      suggest that the penile vacuum device was a successful method for attaining
      penile tumescence; however, the presence of penile tumescence was not accompanied
      by a subjective state of physical or mental sexual arousal. Thus, the mere
      physical presence of an erection does not seem to evoke bodily or mental feelings
      of sexual arousal. It is important to note that these findings suggest that
      attention to the psychosexual components of the individual's sexual experience
      are critical to the subjective experience of sexual arousal and reflect once
      again the multimodal response systems involved in sexual arousal. These results
      suggest that more effective treatment approaches would be based on a clinical
      strategy that provides instruction both on the technical use of a mechanical
      device as well as on the importance of creating an appropriate psychosexual
      environment.

PMID- 11224952
TI  - Human sex-response cycles.
AB  - In order to better assess and explain the multiple factors contributing to our
      patients' sexual difficulties, we need to construct a reasonably simple model of
      human sexual response that illustrates, first, feedback to the mind as it
      orchestrates the sexual response and, second, the concept that sexual experiences
      can be undertaken for reasons that are not strictly sexual but intimacy-based. A
      simple model is presented that integrates responsive and "spontaneous" sexual
      desire, the subsequent creation of further stimuli in the form of the emotions
      experienced, subjective mental excitement, and accurate or inaccurate
      appreciation of physical, genital, and nongenital changes, all of which continue
      to modulate the sexual response.

PMID- 11224953
TI  - Treatment of paraphilia with luteinizing hormone-releasing hormone agonists.
AB  - Up to now there have been no published results of therapy of paraphilia (for
      example, pedophilia or sadism) and sexual aggressive impulsiveness with
      luteinizing hormone-releasing hormone (LHRH) agonists in the German-speaking
      countries. After a short introduction about physiologic features and the present
      state of investigations in treatment of paraphilia with LHRH agonists we describe
      11 patients who were treated with the LHRH agonist Leuprolide Acetate over a
      period of 12 months. The patients showed no tendency toward sexually aggressive
      behavior and reported an evident reduction of penile erection, ejaculation,
      masturbation, sexually deviant impulsiveness, and fantasies. One patient died
      from suicide. In combination with other treatments, LHRH Agonists seem to be a
      very promising alternative to cyproterone acetate and its possible carcinogene
      effects.

PMID- 11224954
TI  - Deception, power, and self-differentiation in college students' romantic
      relationships: an exploratory study.
AB  - The relationships among deception, power, and self-differentiation in college
      students' romantic relationships were explored. As hypothesized, lower total
      deception scores were found to significantly predict higher self-differentiation
      scores. Both men and women reported that men held significantly more power in
      their relationships. A secondary analysis revealed that men were significantly
      more likely than women to indicate they would be inclined to use deceptive
      strategies. Counter to the hypotheses, a significant negative correlation was not
      detected between power scores and omission scores, and positive relationships
      between power scores and contradiction scores were not found.

PMID- 11224955
TI  - Sex-role reversal and clinical judgment of mental health.
AB  - The separation between nonconformist lifestyles and mental disorders plays a
      central role in behavioral therapeutic orientations, where emphasis is put on the
      client's definition of the problem, and in existential and humanistic
      orientations, which encourage the development of the client's individuality. In
      the present study, 621 psychotherapists and students intending to practice
      psychotherapy ranked the mental state of a male client suffering from social
      phobia related to examination situations. Half of the subjects received a case
      history of a law intern (married to a teacher), suffering from social phobia
      related to the oral bar. The other half received a case history of a student in a
      teachers' college (married to a lawyer) suffering from social phobia related to
      being tested in teaching a class. The mental state of the latter has been
      perceived as significantly more severe than that of the former. This difference
      in perception was not related to the subject's sex, professional experience, and
      the frequency of a similar client in their practice. Results are discussed in the
      context of the liberal political attitudes and the secular orientation of the
      subjects.

PMID- 11224957
TI  - School students and general practice.

PMID- 11224956
TI  - Anti-smoking advice from general practitioners: is a population-based approach to
      advice-giving feasible?
AB  - General practitioners' (GPs') advice against smoking has a small, beneficial
      effect on patients' smoking. Consequently, GPs have been urged to adopt a
      population-based approach to advice-giving that involves discussing smoking
      repeatedly with the maximum possible number of smokers. This discussion paper
      assesses how far GPs' current clinical practice is from a population-based
      approach to advice-giving and finds that GPs prefer a problem-orientated approach
      to advising those who present with smoking-related problems. Discussion focuses
      on the feasibility of suggesting that GPs adopt a population-based approach
      instead.

PMID- 11224958
TI  - Complementary medicine.

PMID- 11224959
TI  - Sex, power and echos.

PMID- 11224960
TI  - Job stress and mental health of GPs.

PMID- 11224961
TI  - Breaking the silence.

PMID- 11224962
TI  - Teenagers in primary care--continuing the new direction.

PMID- 11224963
TI  - Exercise: the right prescription in practice.

PMID- 11224964
TI  - The Disability Discrimination Act: an opportunity more than a threat.

PMID- 11224965
TI  - Do the attitudes and beliefs of young teenagers towards general practice
      influence actual consultation behaviour?
AB  - BACKGROUND: Teenagers are believed to have health concerns that are not
      adequately addressed in primary care because of perceived barriers that inhibit
      them from consulting a general practitioner (GP). We report the results of a
      study examining links between potential attitudinal barriers and actual help
      seeking behaviour. AIM: To determine whether the attitudes of teenagers towards
      general practice are associated with differences in consultation patterns.
      METHOD: Results of a postal questionnaire survey of attitudes to general
      practice, performed among teenage patients aged 13 to 15 years registered with
      five general practices in the East Midlands, were analysed in relation to
      consultation data from retrospective casenote analysis for the preceding 12
      months. RESULTS: Matched questionnaire and consultation data were available for
      678 teenagers. We found few significant differences in overall consultation rates
      between teenagers expressing differing attitudes about aspects of general
      practice. Differences did exist in relation to perceived difficulty in getting an
      appointment, feeling able to confide in a GP, and perception of adequate time
      being given in the consultation. Fear of embarrassment was associated with lower
      consultation rates for gynaecological problems and contraception. CONCLUSIONS:
      Negative perceptions of general practice by teenagers may have less of an
      influence on actual consultation behaviour than previously believed. However,
      there are some aspects of care that merit further attention if teenagers are to
      feel able to consult their GP more easily.

PMID- 11224966
TI  - What is the magnitude of blood pressure response to a programme of moderate
      intensity exercise? Randomised controlled trial among sedentary adults with
      unmedicated hypertension.
AB  - BACKGROUND: Current guidelines for the management of hypertension recommend
      regular, moderate intensity aerobic exercise such as brisk walking as a means of
      blood pressure reduction. However, there is a lack of consistent evidence
      regarding the magnitude of blood pressure response to such a prescription. In
      particular, no well designed studies have investigated the efficacy of a
      programme of exercise meeting current guidelines. AIM: To investigate the effect
      of a six-week programme of moderate intensity exercise on daytime ambulatory
      blood pressure (10.00 am to 10.00 pm) among unmedicated, sedentary adults aged 25
      years to 63 years with office blood pressure of 150 mmHg to 180 mmHg systolic
      and/or 91 mmHg to 110 mmHg diastolic. METHOD: Randomised controlled trial of
      participants carrying out 30 minutes of moderate intensity exercise (brisk
      walking or equivalent) five days per week for six weeks compared with controls
      who maintained existing levels of physical activity. RESULTS: Compliance with the
      exercise programme was high. The reduction in mean daytime ambulatory blood
      pressure between baseline and six-week follow-up was greater in the intervention
      group than in the control group for both systolic and diastolic blood pressure.
      However, this net hypotensive effect was not statistically significant (systolic
      = -3.4 mmHg, 95% CI = -7.4 to 0.6; diastolic = -2.8 mmHg, 95% CI = -5.8 to 0.2).
      Adjusting for baseline differences in mean ambulatory blood pressure in an
      analysis of covariance led to a reduction in the estimated magnitude of the
      effect (systolic = -1.9 mmHg, 95% CI = -5.4 to 1.7, P = 0.31; diastolic = -2.2
      mmHg, 95% CI = -4.9 to 0.5, P = 0.11). CONCLUSION: Despite high compliance with
      the exercise programme, the magnitude of the hypotensive effect of moderate
      intensity exercise was not as great as that found in studies of higher intensity
      exercise among hypertensives. Expectations of general practitioners and patients
      that a programme of moderate intensity exercise will lead to a clinically
      important reduction in the individual's blood pressure are unlikely to be
      realised.

PMID- 11224967
TI  - Reducing therapist contact in cognitive behaviour therapy for panic disorder and
      agoraphobia in primary care: global measures of outcome in a randomised
      controlled trial.
AB  - BACKGROUND: Panic disorder, with and without agoraphobia, is a prevalent
      condition presenting in general practice. Psychological treatments are effective
      but are limited by restricted availability. Interest has grown in methods by
      which the efficiency and thus availability of psychological treatments can be
      improved, with particular emphasis on reduced therapist contact formats. AIM: To
      evaluate the relative efficacy in a primary care setting of a cognitive behaviour
      therapy (CBT) delivered at three levels of therapist contact: standard contact,
      minimum contact, and bibliotherapy. METHOD: A total of 104 patients were randomly
      allocated to receive standard therapist contact, minimum therapist contact or
      bibliotherapy, with 91 patients completing treatment. All patients received an
      identical treatment manual and were seen by the same psychologist therapist.
      Outcome was reported in terms of brief global ratings of severity of illness,
      change in symptoms, and levels of social disruption. These brief measures were
      chosen to be suitable for use in general practice and were used at treatment
      entry and endpoint. RESULTS: The standard therapist contact group had the
      strongest and most comprehensive treatment response, showing significant
      differences from the bibliotherapy group on all, and the minimum therapist
      contact group on some, endpoint measures. Some reduction in efficacy was
      therefore found for the reduced therapist contact groups. CONCLUSION: The
      standard therapist contact group showed the greatest treatment efficacy in the
      present study. As it was of notably shorter duration than many other current
      formulations of CBT, it represents a useful and efficient treatment for panic
      disorder and agoraphobia in primary care.

PMID- 11224968
TI  - The two-dose measles, mumps, and rubella (MMR) immunisation schedule: factors
      affecting maternal intention to vaccinate.
AB  - BACKGROUND: In the light of sub-optimal uptake of the measles, mumps, and rubella
      (MMR) vaccination, we investigated the factors that influence the intentions of
      mothers to vaccinate. METHOD: A cross-sectional survey of 300 mothers in
      Birmingham with children approaching a routine MMR vaccination was conducted
      using a postal questionnaire to measure: intention to vaccinate, psychological
      variables, knowledge of the vaccine, and socioeconomic status. The vaccination
      status of the children was obtained from South Birmingham Child Health
      Surveillance Unit. RESULTS: The response rate was 59%. Fewer mothers approaching
      the second MMR vaccination (Group 2) intended to take their children for this
      vaccination than Group 1 (mothers approaching the first MMR vaccination) (Mann
      Whitney U = 2180, P < 0.0001). Group 2 expressed more negative beliefs about the
      outcome of having the MMR vaccine ('vaccine outcome beliefs') (Mann-Whitney U =
      2155, P < 0.0001), were more likely to believe it was 'unsafe' (chi 2 = 9.114, P
      = 0.004) and that it rarely protected (chi 2 = 6.882, P = 0.014) than Group 1.
      The commonest side-effect cited was general malaise, but 29.8% cited autism. The
      most trusted source of information was the general practitioner but the most
      common source of information on side-effects was television (34.6%). Multiple
      linear regression revealed that, in Group 1, only 'vaccine outcome beliefs'
      significantly predicted intention (77.1% of the variance). In Group 2 'vaccine
      outcome beliefs', attitude to the MMR vaccine, and prior MMR status all predicted
      intention (93% of the variance). CONCLUSION: A major reason for the low uptake of
      the MMR vaccination is that it is not perceived to be important for children's
      health, particularly the second dose. Health education from GPs is likely to have
      a considerable impact.

PMID- 11224969
TI  - Frequent attenders' consulting patterns with general practitioners.
AB  - BACKGROUND: Despite the growing literature on frequent attendance, little is
      known about the consulting patterns of frequent attenders with different doctors.
      To develop appropriate intervention strategies and to improve the clinical care
      of frequent attenders, a full understanding of these consulting patterns is
      essential. AIMS: This paper has three aims: to determine whether frequent
      attenders consult more with some doctors than others; to determine how many
      different doctors frequent attenders consult with; and to determine whether
      frequent attenders exhibit greater continuity of care than non-frequent
      attenders. METHOD: Analysis of a validated dataset of 592,028 consultations made
      by 61,055 patients from four practices over 41 months. Comparisons between the
      consulting patterns of the frequent attenders, defined as the most frequently
      consulting 3% of the population by practice, with non-frequent attenders and the
      overall practice populations. RESULTS: There was considerable variation in the
      numbers and proportions of consultations with frequent attenders between
      individual doctors. Most of the frequent attenders consulted with most or all of
      the doctors within practices over the timeframe. Frequent attenders exhibited
      more continuity of care than non-frequent attenders. CONCLUSION: The reasons why
      some doctors have more consultations with frequent attenders is unclear. Some
      doctors may actively encourage frequent attendance. While many frequent attenders
      have clear allegiances to one doctor, many also consult widely with a large
      number of doctors. The consequences of such behaviour are unknown. These findings
      have important implications in the development of appropriate interventions for
      reducing problematic frequent attendance.

PMID- 11224970
TI  - What role for the general practitioner in child protection?
AB  - BACKGROUND: New government guidance on cooperation in child protection confirms
      the importance of the general practitioner (GP) contribution. While research
      highlights the concerns of others about their role in the multi-agency process,
      relatively little is known about the views and experiences of GPs themselves.
      AIM: To examine the understanding that each of the key professional groups had of
      its own and each other's roles in child protection to identify those factors seen
      to enhance or inhibit the effective performance of these roles. METHOD: The
      research formed part of a larger investigation of the role of health
      professionals in child protection, which combined case study investigations of
      child protection networks in three health authority sites with a regional survey
      of Area Child Protection Committee members. RESULTS: A lack of correspondence was
      identified between GPs' perception and performance of their role in child
      protection and the expectations placed upon them by other child protection
      professionals and government guidance. CONCLUSION: The study identifies the need
      for more explicit discussion of the nature and extent of the GP role in local
      interagency child protection networks.

PMID- 11224971
TI  - Is participation in research as an investigator an effective form of continuing
      medical education?
AB  - Continuing medical education and research are a daily necessity for general
      practitioners (GPs). This study investigated the possibility that participation
      in research is an effective form of continuing medical education. Although there
      was an indication that some modification of GPs' knowledge and skills had
      occurred, it was not possible to conclude that this was entirely due to
      participation in research.

PMID- 11224972
TI  - A pilot study of primary care workers with a disability.
AB  - Eighty practice managers identified 55 colleagues with disabilities in a postal
      survey. Most of the 15 people with disabilities who were subsequently interviewed
      described colleagues having helpful attitudes but changes had not been made to
      practice workplaces or systems to retain them at work. Proactive support for
      disabled workers might improve retention in the National Health Service
      workforce.

PMID- 11224973
TI  - Hormone replacement therapy: the views of general practitioners and practice
      nurses.
AB  - The knowledge and attitudes of primary healthcare professionals have been cited
      as barriers to appropriate uptake of hormone replacement therapy (HRT). This
      questionnaire survey of general practitioners and practice nurses revealed
      positive attitudes to HRT but uncovered a lack of pharmacological knowledge.

PMID- 11224974
TI  - Prevalence of enduring and disabling mental illness in the inner city.
AB  - Previous research identifying the long-term mentally ill in primary care has been
      outside areas of deprivation. We used a case finding approach by a primary care
      group to identify the prevalence and characteristics of people with enduring and
      disabling mental ill health in a disadvantaged inner-city community. We found a
      high point prevalence (12.9 per 1000 patients) of enduring psychotic and non
      psychotic illness (36.1% and 63.9% respectively). This contributed to
      considerable workload and disability, and included a significant proportion of
      older people (24.6% aged over 65 years). The approach may be useful for local
      needs assessment. It highlights a need to consider disability as well as
      diagnosis for service development.

PMID- 11224975
TI  - Diagnosis and general practice.
AB  - This discussion paper presents the case for a rigorous diagnostic research agenda
      within primary care. In view of unique aspects of primary care medicine and the
      relatively unselected nature of the populations encountered by general
      practitioners, it is clear that diagnostic research undertaken in other settings
      may be inapplicable. Most diagnostic studies adopt designs that seek to compare
      items, or clusters of items, of clinical information against a gold standard. In
      order to enhance the feasibility and rigour of such research within primary care,
      suggestions are made about priorities and specific key methodological issues. It
      is essential that the information generated by primary care diagnostic research
      should be reliable, valid, useful, and useable within general practice. The
      ultimate objective must be the identification of specific items, or small
      clusters of items, of clinical information of high discriminant ability among the
      groups of patients encountered in general practice.

PMID- 11224976
TI  - The Navajo Healing Project.

PMID- 11224977
TI  - Identity and healing in three Navajo religious traditions: sa'ah naaghai bik'eh
      hozh [symbol: see text].
AB  - In this article, we elucidate how the Navajo synthetic principle sa'ah naaghai
      bik'eh hozh [symbol: see text] (SNBH) is understood, demonstrated, and elaborated
      in three different Navajo healing traditions. We conducted interviews with Navajo
      healers and their patients affiliated with Traditional Navajo religion, the
      Native American Church, and Pentecostal Christianity. Their narratives provide
      access to cultural themes of identity and healing that invoke elements of SNBH.
      SNBH specifies that the conditions for health and well-being are harmony within
      and connection to the physical/spiritual world. Specifically, each religious
      healing tradition encourages affective engagement, proper family relations, an
      understanding of one's cultural and spiritual histories, and the use of kinship
      terms to establish affective bonds with one's family and with the spiritual
      world. People's relationships within this common behavioral environment are
      integral to their self-orientations, to their identities as Navajos, and to the
      therapeutic process. The disruption and restoration of these relationships
      constitute an important affective dimension in Navajo distress and healing.

PMID- 11224978
TI  - The whole universe is my cathedral: a contemporary Navajo spiritual synthesis.
AB  - This article discusses the three major spiritual healing ways used by Navajo
      Indians today: Traditional healing practices that have been used for generations
      and still have a dynamic existence relevant to everyday Navajo life; Christian
      healing traditions, ranging from Catholic Charismatic to Protestant Pentecostal;
      and practices of the Native American Church (NAC). The complex relationship among
      these healing traditions on the Navajo reservation is examined through a case
      study of a Navajo woman whose personal spirituality includes all three. Faced
      with serious medical problems, this devout Catholic turned to Navajo Traditional
      and Native American Church spiritual diagnosis and treatment. This analysis is
      the occasion for a reflection on the contemporary relevance of the kind of
      spiritual synthesis characterized in this woman's experience.

PMID- 11224979
TI  - Jesus, peyote, and the holy people: alcohol abuse and the ethos of power in
      Navajo healing.
AB  - Of the three religious healing traditions that coexist within the contemporary
      Navajo health care system, the Native American Church (NAC) and Pentecostal
      Christianity are more actively involved in the treatment of alcohol and substance
      abuse than is Traditional Navajo healing. This article examines these two more
      recent healing traditions as religious responses to the contemporary Navajo
      crisis of alcohol and substance abuse as well as to socioeconomic changes. These
      traditions offer new kinds of power, social networks, and personal meaning that
      facilitate a transformation of self, a revitalized sense of community, and a new
      vision of the possibilities of the future for Navajo people who suffer. Examining
      the ethos of power that underlies Navajo healing can complement the theoretical
      emphasis on harmony and beauty in anthropological research on Navajo culture and
      religion.

PMID- 11224980
TI  - Rethinking the role of diagnosis in Navajo religious healing.
AB  - Diagnosis plays a central, primary role in the therapeutic process across
      cultures. In this article, the authors examine the role of diagnosis in two
      Navajo religious healing traditions, the Traditional Navajo religion and the
      Native American Church (NAC), and examine a case study of a diagnostic encounter
      between an NAC diagnostician and a Traditional patient. The authors assert that,
      for Navajos, diagnosis is not merely a prescriptive rite that passively initiates
      the therapeutic process (as it has been seen in the Navajo literature) but can
      itself constitute a cure. Claims made about the similarity between Western
      psychotherapy and religious healing both by scholars and by the healer and
      patient in this case study are investigated. The authors conclude that such an
      analogy must be seen against the backdrop of Navajo beliefs about thought,
      speech, and health. Viewing diagnosis as a "talking cure" and an example of
      Good's concept of "narrativizing" illness (things it shares with Western
      psychotherapy) suggests why the analogy is appealing for Navajos themselves.

PMID- 11224981
TI  - Depressive illness and Navajo healing.
AB  - What is the experience of Navajo patients in Navajo religious healing who, by the
      criteria and in the vernacular of contemporary psychiatry, would be diagnosed
      with the disorder called depression? We ask this question in the context of a
      double dialogue between psychiatry and anthropology and between these
      disciplines' academic constructs of illness and those of contemporary Navajos.
      The dialogue is conducted in the arena of patient narratives, providing a means
      for observing and explicating processes of therapeutic change in individuals, for
      illustrating variations in forms of Navajo religious healing sought out by
      patients demonstrating similar symptoms of distress, and for considering the
      heuristic utility of psychiatric diagnoses and nomenclature in the
      conceptualization of illness, recovery, and religious healing. From among the 37
      percent of patients participating in the Navajo Healing Project who had a
      lifetime history of a major depressive illness, three are discussed herein, their
      selection based on two criteria: (1) all met formal psychiatric diagnostic
      criteria for a major depressive episode at the time of their healing ceremonies,
      and (2) together, their experiences illustrate the range of contemporary Navajo
      religious healing, including Traditional, Native American Church (NAC), and
      Christian forms. We suggest that, despite the explicit role of the sacred in
      religious healing interventions available to Navajo patients, differences between
      biomedical and religious healing systems may be of less significance than their
      shared existential engagement of problems such as those glossed as depression.

PMID- 11224982
TI  - Comments on the Navajo Healing Project.

PMID- 11224983
TI  - The efficacy of traditional medicine: current theoretical and methodological
      issues.
AB  - The efficacy of traditional medicine is an issue that continues to vex medical
      anthropology. This article critically examines how the efficacy of traditional
      medicine has been conceived, operationalized, and studied and argues that a
      consensus remains elusive. Efficacy must be seen as fluid and shifting, the
      product of a negotiated, but not necessarily shared, understanding by those
      involved in the sickness episode, including physicians/healers, patients, and
      members of the community. Medical anthropology needs to return to the field to
      gather more data on indigenous understandings of efficacy to counteract the
      biases inherent in the utilization of biomedical understandings and methods
      characteristic of much previous work.

PMID- 11224985
TI  - Radiation therapy for non-small cell lung cancer (NSCLC).

PMID- 11224984
TI  - Biological considerations in lung cancer.
AB  - Our understanding of lung cancer biology has rapidly expanded in recent years.
      Lung cancer, unlike most human cancers, can be traced to an environmental risk
      factor in the majority of cases, and this fact is reflected in the vast number of
      genetic alterations discovered in lung tumors whose pathogenesis is believed to
      be mediated by carcinogen exposure. The discovery of these alterations has led to
      a greater understanding of tumor development. The dramatic progress in the
      understanding of the genetic and molecular basis of oncogenesis and the induction
      of immunity has led to a rejuvenation of efforts to apply this new knowledge to
      this common and refractory disease. Further, the resurgent interest in cancer
      immunology and tumor-host interactions holds promise for the development of new
      approaches to treatment based on harvesting the immune systems ability to
      recognize these alterations. Hopefully, this understanding will lead to novel
      approaches with real and convincing clinical efficacy once some of these
      strategies are tested in carefully performed randomized clinical trials with
      appropriate power to detect meaningful differences.

PMID- 11224986
TI  - Combined modality therapy for early stage operable and locally advanced
      potentially resectable non-small cell lung carcinoma.

PMID- 11224987
TI  - Chemoradiation in locally advanced non-small cell lung cancer.

PMID- 11224988
TI  - Lung cancer: therapeutic options for stage IV and recurrent NSCLC.

PMID- 11224989
TI  - Therapy of limited stage small cell lung cancer.

PMID- 11224990
TI  - Treatment of extensive stage small cell lung cancer.
AB  - Over the past twenty years combination chemotherapy has continued to produce
      small survival gains for patients with SCLC. We enter the next century
      enthusiastic about the array of new chemotherapeutic agents to evaluate and
      fascinated by the biological agents with the hope of achieving dramatic
      improvements in survival for our patients with SCLC.

PMID- 11224991
TI  - Thymic malignancies.
AB  - Thymomas and thymic carcinomas are unique tumors of the anterior mediastinum. The
      association of a variety of different paraneoplastic syndromes with such lesions
      has fascinated physicians and researchers for years. Most recently, it has been
      demonstrated by numerous authors that thymomas are chemosensitive tumors. Their
      indolent nature and relative rarity have made evaluation through prospective
      randomized clinical trials extremely difficult. Further information regarding the
      molecular nature of these neoplasms and immunologic aspects is needed in future
      investigation.

PMID- 11224992
TI  - Germ cell neoplasms and other malignancies of the mediastinum.

PMID- 11224993
TI  - The epidemiology of lung cancer.
AB  - Lung cancer continues to be the leader in cancer deaths in the United States. The
      incidence of lung cancer in men has slowly decreased since the late 1980s, but
      has just now begun to plateau in women at the end of this decade. Despite modest
      advances in chemotherapy for treating lung cancer, it remains a deadly disease
      with overall 5-yr survival rates having not increased significantly over the last
      25 years, remaining at approximately 14%. Tobacco smoking causes approximately 85
      90% of bronchogenic carcinoma. Environmental tobacco exposure or a second-hand
      smoke also may cause lung cancer in life-long non-smokers. Certain occupational
      agents such as arsenic, asbestos, chromium, nickel and vinyl chloride increase
      the relative risk for lung cancer. Smoking has an additive or multiplicative
      effect with some of these agents. Familial predisposition for lung cancer is an
      area with advancing research. Developments in molecular biology have led to
      growing interest in investigation of biological markers, which may increase
      predisposition to smoking-related carcinogenesis. Hopefully, in the future we
      will be able to screen for lung cancer by using specific biomarkers. Finally,
      dietary factors have also been proposed as potential risk modulators, with
      vitamins A, C and E proposed as having a protective effect. Despite the slow
      decline of smoking in the United States, lung cancer will likely continue its
      devastation for years to come.

PMID- 11224994
TI  - Malignant pleural mesothelioma.
AB  - Malignant pleural mesothelioma remains a difficult tumor to treat, much less
      cure. Currently, the best chance for long-term survival lies with early diagnosis
      and aggressive surgical extirpation, but given the typically long delay between
      the onset of symptoms and diagnosis, this is only possible with a high index of
      suspicion and an aggressive diagnosis workup. Early referral to a tertiary center
      experienced in the treatment of MPM may be important for several reasons: (1)
      decreased risk of tumor spread along multiple thoracenesis/biopsy tracts, (2) the
      availability of specialized pathologic assays for definitive diagnosis, (3) the
      availability of critical staging modalities (aggressive mediastinoscopy +/-
      thoracoscopy, MRI scans performed according to specific mesothelioma protocols,
      and perhaps PET scans), (4) surgical experience with pleurectomy/decortication
      and/or extrapleural pneumonectomy, that may decrease morbidity and mortality, and
      (5) the availability of novel adjuvant protocols. Single-modality therapy is
      unlikely to result in long-term survival. Aggressive surgery is required for
      optimal debulking, and extrapleural pneumonectomy may offer better local control
      compared with pleurectomy/ecortication. Delivery of optimal radiation schedules,
      which may involve large fractions as well as large total doses, is limited by the
      presence of nearby dose-limiting structures. Current chemotherapy is severely
      lacking in producing objective responses and improved survival although
      gemcitabine and IL-2 may be active agents to be combined with radiation and/or
      other agents. Hyperthermia, photodynamic therapy, intracavitary therapy, and gene
      therapy are all relatively new techniques under active investigation that should
      be supported by enrollment in on-going protocols. Predictably, many of these
      techniques provide greater benefit when used in the setting of adjuvant protocols
      or minimal residual disease, emphasizing the importance of multimodality therapy.

PMID- 11224995
TI  - Epidemiology, diagnosis, and staging of esophageal cancer.

PMID- 11224996
TI  - Therapy for esophageal cancer.

PMID- 11224998
TI  - Surgery for non-small cell lung cancer.

PMID- 11224997
TI  - Staging and prognosis in lung cancer: making the complex accessible.

PMID- 11224999
TI  - Agent identification and preclinical testing.

PMID- 11225000
TI  - Chemoprevention in prostate cancer.

PMID- 11225001
TI  - Chemoprevention of breast cancer.

PMID- 11225002
TI  - Chemoprevention of colon cancer.

PMID- 11225003
TI  - Lung cancer.

PMID- 11225004
TI  - Chemoprevention in head and neck cancer.

PMID- 11225005
TI  - Chemoprevention of superficial bladder cancer.
AB  - The development, evaluation and approval of promising agents for bladder cancer
      prevention (chemoprevention)depends upon the rational integration of  four key
      components: a) Agents (pharmaceuticals, biologics and nutrients); b) Biomakers
      (intermediate endpoints that predict for clinical response and risk reduction; c)
      Cohorts (well defined high risk target populations d) Designs (efficient trial
      designs linked to the clinical phase of development).  The promise of this
      overall strategy is the ability to conduct faster, smaller and more cost
      effective trials which incorporate validated surrogate endpoints rather than
      conventional clinical endpoints (cancer incidence, recurrence and survival). 
      Current National Cancer Institute (NCI) phase III bladder cancer chemopreventive
      trials in progress are described.   Since most patients with  superficial
      (transitional cell) bladder cancer present with early disease (Ta, T1, Tis
      lesions) that frequently recurs and is easily accessible by serial cystoscopy and
      urine cytology, bladder cancer serves as a powerful clinical for conducting
      prevention trials of new agents for a tobacco related malignancy.

PMID- 11225006
TI  - Chemoprevention of skin cancer.

PMID- 11225007
TI  - The role of vaccines in cancer prevention.

PMID- 11225008
TI  - Intermediate biomarkers.

PMID- 11225009
TI  - Tissue microdissection and processing.

PMID- 11225010
TI  - Basic pharmacokinetics and pharmacodynamic principles.

PMID- 11225011
TI  - Job interview or horror movie?

PMID- 11225012
TI  - Using a psychrometric chart for IAQ--Part II. This century-old approach remains
      useful for OH&S professionals.

PMID- 11225013
TI  - Online help for a busy HR staff.

PMID- 11225014
TI  - Helmets under the updated ARFF standard.

PMID- 11225015
TI  - Preventing construction fires.

PMID- 11225016
TI  - Building safety into a loading dock.

PMID- 11225017
TI  - Building a training tool--together.

PMID- 11225018
TI  - Avoiding the conFINES.

PMID- 11225019
TI  - The cost of comp.

PMID- 11225020
TI  - Talking dollars & sense.

PMID- 11225022
TI  - The last word on contacts.

PMID- 11225021
TI  - Achieving 'sustained customer satisfaction'.

PMID- 11225023
TI  - [Emphasis on tuberculosis complicated with HIV/AIDS].

PMID- 11225024
TI  - [Current status on animal model of bronchial asthma].

PMID- 11225025
TI  - [Diagnosis and management of nontuberculous mycobacteriosis].

PMID- 11225026
TI  - [Epidemiology of tuberculosis complicated with HIV infection and AIDS].

PMID- 11225027
TI  - [Diagnosis of tuberculosis complicated with HIV infection and AIDS].

PMID- 11225028
TI  - [Managements of tuberculosis complicated with HIV infection and AIDS].

PMID- 11225029
TI  - [A clinical research on human immunodeficiency virus seropositive patients with
      pulmonary tuberculosis].
AB  - OBJECTIVE: To improve the awareness of human immunodeficiency virus (HIV)
      infection in patients with pulmonary tuberculosis (PTB). METHODS: 168 cases of
      HIV-positive PTB in Bata Regional Hospital, Guinea Equatorial from January 1996
      to November 1999 were analyzed. RESULTS: HIV seroprevalence rose from 11.4% in
      1996 to 22.7% in 1999. Analysis of clinical findings showed that majority of the
      cases showed acute onset (94.6%). Recent weight loss (82.1%), joints pain
      (78.6%), skin itching (42.9%), chronic diarrhea (23.2%), generalized
      lymphadenopathy (20.8%) and dermatosis (13.1%) were the frequent symptoms and
      signs. The chest X-rays showed that the atypical radiographic patterns (63.3%).
      The positive rate of sputum for acid fast bacilli was 58.3%. At the end of six
      months of antituberculosis chemotherapy (2SHRZ/4HRZ), all of the survival
      patients improved in the clinical symptoms and signs, and laboratory and X-rays.
      The mortality rate was significantly higher in HIV-positive PTB (27.4%) patients
      than in HIV-negative patients (9.2%). CONCLUSIONS: Physician should be alert of
      the occurrence of HIV-associated PTB. Direct smear examination of sputum and
      chest X-rays are the best methods for the rapid and correct diagnosis. Short
      course chemotherapy of 6 months is as effective in HIV-positive patients as in
      HIV-negative patients.

PMID- 11225030
TI  - [Resistance and efficacy of treatment in relapse pulmonary tuberculosis].
AB  - OBJECTIVE: To investigate the resistant status and factors involved and to
      evaluate the efficacy of treatment in relapse pulmonary tuberculosis. METHODS:
      The analysis of history of chemotherapy and resistant status in 448 relapse
      pulmonary tuberculosis cases with culture positive and susceptibility test was
      conducted. All new registered relapse cases during 1988-1997 in Beijing were
      treated with regimen of 2RHZS(E)/4RHE or 2RHZS(E)/6RH under fully supervision and
      prognosis was evaluated with cohort analysis. RESULTS: Of 448 relapse cases 153
      (34.2%) were resistant at least to 1 antituberculosis drug, 20.9% resistant to
      INH, 17.6% to SM, 11.1% to RFP, 7.8% to PAS, 2.9% to EMB and 6.2% resistant to
      both INH and RFP. The resistance rates in the cases of compliance and default in
      initial treatment were 22.3% and 55.8%, respectively, and resistance to RFP were
      6.3% and 20.8% respectively. The sputum conversion rate in relapse cases during
      1988-1997 were 80.5%-89.6%. CONCLUSIONS: The resistant rate in relapse cases in
      Beijing was 34.1%. The higher compliance in the chemotherapy, the lower resistant
      rate, conversely the higher default the higher resistance. The majority of
      resistant cases were resistant to INH, SM and RFP, and it is important in making
      a rational regimen.

PMID- 11225031
TI  - [Study on mRNA differential display in Mycobacterium tuberculosis H37Rv and
      H37Ra].
AB  - OBJECTIVE: To study genetic differences between H37Rv and H37Ra by mRNA
      differential display, paving the way for obtaining virulence-related gene of
      Mycobacterium tuberculosis (MTB). METHODS: Total RNA was extracted from MTB H37Rv
      and H37Ra, mRNA differential display was conducted following reverse
      transcription, polymerase chain reaction, polyacrilamide gel electrophoresis and
      radiography. The differential bands were recovered, reamplified, sequenced, and
      then homologous query was done. RESULTS: 10 differential bands between H37Rv and
      H37Ra were recovered, 2 of which were homologous to H37Rv DNA after query from
      NCBI database of GenBank. CONCLUSIONS: mRNA differential display is an effective,
      sensitive method, can display differences between different strains intra- and
      extra-species and be used in searching Mycobacterium tuberculosis virulence
      related gene. Obtained differential bands in this study may cover MTB virulence
      related gene.

PMID- 11225032
TI  - [Production, characterization and purification of monoclonal antibodies against
      antigens of Mycobacterium tuberculosis H37Rv strain].
AB  - OBJECTIVE: Using monoclonal antibody (McAb) technique to analyze polypeptide
      antigens of Mycobacterium strains and try to find out the best method for
      purification of McAb. METHODS: McAbs against H37Rv strain were produced by
      routine procedure. McAb-producing hybridomas were detected by ELISA and
      immunoblots technique. 24 strains of mycobacterium were grown on Loewenstein
      Jensen medium for 1 to 3 weeks at 37 degrees C. H37Rv strain were grown on
      Loewenstein-Jensen medium or Sauton liquid medium. Ammonium sulfate, caprylic
      acid precipitation and ion exchange chromatography methods were used to purify
      McAbs against antigens of H37Rv strain. RESULTS: 14 McAb-produing hybridomas were
      obtained. C2 McAb reacted with all 24 strains of mycobacterium and 7C12 only
      reacted with H37Rv, H37Ra, M. bovis, BCG strains, C2 and 7C12 reacted with
      secreted proteins of H37Rv strain. 40,000/38,000 antigen of H37Rv strain was
      expressed differently in Loewenstein-Jensen medium and Sauton liquid medium.
      Relative activity of all McAbs was between 10(-4)-10(-7). The results of purified
      McAb showed that ammonium sulfate precipitation method could have the highest
      rate of recovery. Ion exchange chromatography method could have the highest
      purity. Caprylic acid method can remove albumin effectively and the purification
      of McAbs in ascific fluid was simple and easy to perform. CONCLUSIONS:
      Polypeptide antigens of H37Rv against by C2, 7C12 McAb were the secreted
      proteins. For purification of McAb, the results suggested that ion exchange
      chromatography method can be applied for analysis and caprylic acid method for a
      very large volume of ascitic fluid.

PMID- 11225033
TI  - [Detection of Mycoplasma genitalium in throat by nested polymerase chain reaction
      and analysis of DNA sequencing in pediatric patients with acute upper respiratory
      tract infections].
AB  - OBJECTIVE: To explore the relation between Mycoplasma genitalium (Mg) and acute
      upper respiratory tract infection in pediatric patients by using nested
      polymerase chain reaction(nPCR) and analysis of DNA sequencing techniques.
      METHODS: The specimens of throat swab were obtained in 62 acute upper respiratory
      tract infections children and 80 health children. The two kinds of Mg species
      specific, in which the sequences of I-III and V-VII variable regions of Mg 16Sr
      RNA gene were detected by using nPCR technique. DNA sequences of positive product
      were detected and analysed. RESULTS: The Positive rate of health children is 5%
      (4/80), while the acute upper respiratory tract infection children is 21%
      (13/62). The difference is significant (P < 0.001). The DNA sequences of positive
      product shows that: there are two point mutation(T-->C) in the sequences of V-VII
      variable regions of throat swab of one pediatric patient, other sequences are
      same as those Mg type strain(G-37T). CONCLUSIONS: Acute upper respiratory tract
      infection of pediatric patients have relation with Mg. There are Mg mutant strain
      in China.

PMID- 11225034
TI  - [Detection and significance of HPV16, 18 infection, P53 overexpression and
      telomerase activity in patients with lung cancer].
AB  - OBJECTIVE: To investigate if HPV16, 18 infection, P53 expression and telomerase
      activity have the differences among different ethnic patient groups with lung
      cancer, and their significance. METHODS: HPV16, 18-DNA, P53 protein
      overexpression in 110 specimens of lung cancer were detected by PCR and
      immunohistochemistry, respectively. And telomerase activity in 22 specimens of
      fresh lung cancer tissues was detected by PCR-TRAP. RESULTS: The positive rate of
      HPV16, 18-DNA in the lung cancer group was higher than the normal tissues group
      and inflammatory lesions group (all P < 0.01). The positive rate of P53 protein
      overexpression was 57% in the lung cancer group, negative in the normal tissues
      group (P < 0.01). The differences of HPV16, 18 infection and P53 overexpression
      have no statistic significance among different ethnic groups (all P > 0.05). The
      telomerase activity was higher in the cancer tissues (86%) compared with the
      adjacent normal tissues (22%, P < 0.01). CONCLUSIONS: HPV16, 18 infection might
      have etiologic significance for lung cancer and make p53 gene overexpression to
      cause carcinogenesis, but each might have its own carcinogenic process. The high
      telomerase activity could be a marker of biomolecular change in lung cancer. The
      different ethnic background of HPV16, 18 infection and P53 overexpression of lung
      cancer need to do further study with a large number of specimens in the future.

PMID- 11225035
TI  - [Effects of permissive hypercapnia on pulmonary mechanics and hemodynamics in
      sheep with acute lung injury].
AB  - OBJECTIVE: To study the effects of permissive hypercapnia (PHC) on pulmonary
      mechanics and hemodynamics in sheep with acute lung injury (ALI). METHODS: In 18
      sheep with LPS induced ALI, gas exchange, pulmonary mechanics and hemodynamics
      were observed at different tidal volumes (VT). RESULTS: When VT was decreased
      from 16 ml/kg to 4-7 ml/kg, PHC was induced. Arterial pressure of carbon dioxide
      increased markedly, arterial oxygen pressure, oxygen saturation and mixed venous
      oxygen saturation decreased (P < 0.05). Airway pressure decreased significantly
      (P < 0.05), but the airway resistance increased. Systemic and pulmonary vascular
      resistance index, right and left ventricular stroke work index increased in PHC,
      but heart rate decreased (P < 0.05). Compared with VT 16 ml/kg, cardiac index
      decreased markedly in PHC. In static pressure-volume curve, the pressure of upper
      inflection point was (21.8 +/- 3.2) cm H2O, volume was (10.7 +/- 1.3) ml/kg.
      CONCLUSIONS: Alveolar overdistention may be prevented only when airway plateau
      pressure is less than 20-25 cm H2O, but cardiac index is decreased.

PMID- 11225036
TI  - [Analysis of death of hospitalized patients with asthma in 16 hospitals in
      Beijing from 1988 to 1998].

PMID- 11225037
TI  - [Comparative studies of treatments with cefepime and ceftazidime in patients with
      pneumonia].

PMID- 11225038
TI  - [Resistance to rifampin of mycobacterium tuberculosis and rpoB gene].

PMID- 11225039
TI  - [Detection and significance of polymerase chain reaction in Mycobacterium
      tuberculosis in patients with tuberculosis].

PMID- 11225040
TI  - [Multi-peptides growth factor expression in asthma model rats and effect of
      dexamethasone on its expressions].

PMID- 11225041
TI  - [Study on airway responsiveness in asthma and obstructive lung disease].

PMID- 11225046
TI  - Disavowal of the behaviorist paradigm in nursing education: what makes it so
      difficult to unseat?
AB  - The literature is replete with calls for disavowal of the behaviorist paradigm in
      nursing education, a paradigm charged with producing successive generations of
      passive learners who are incapable of instigating much needed and long overdue
      reforms within the health care system. Only rarely has this call been challenged
      by nurse educators. In this article, the role of a paradigm in delineating the
      nature of and solutions to significant problems within a scientific community is
      explored. I posit that the current eschewal of behaviorism by nurse educators
      stems not from its failure to solve significant problems in nursing education but
      rather from an apparent shift in value orientation--a shift from effecting
      learning (and health) outcomes to effecting social change. Despite this seeming
      shift in values, effecting learning outcomes is still held to be an essential
      aspect of nursing education, and it is because of this, I argue, that the
      behaviorist paradigm is so difficult to unseat.

PMID- 11225047
TI  - They took the time ... they started to care: stories of African-American nursing
      students in intercultural caring groups.
AB  - Socially responsible nurse educators articulate the need to explore opportunities
      for nursing students to participate in experiences that promote caring and
      respect for diversity. This research illuminates the experiences of 10 African
      American nursing students who participated in caring groups while enrolled in a
      predominantly White nursing education program. Although the meanings embedded in
      the African-American students' stories revealed commonalities with those of
      European-American and international students, there were also some differences.
      The authors maintained a critical social consciousness to analyze and describe
      these commonalities and differences. This article discusses the constitutive
      patterns and themes that emerged from the data and addresses implications for
      nursing education and practice.

PMID- 11225048
TI  - Advancing health policy in nursing education through service learning.
AB  - Knowledge of health policy is an increasingly important aspect of nursing
      practice and education, especially as nurses strive to improve the rapidly
      changing health care delivery system. At the same time, many educators,
      researchers, foundations, and government officials are touting the benefits of
      service learning. In particular, service learning offers ways to enhance
      partnerships between academia and community agencies and to extend learning
      beyond the traditional classroom. We present a model for educating nurses as
      advanced practice nurses in health policy that links service learning with a
      framework for the political development of nurses. Under the rubric of service
      learning, the curriculum is based on the overlap among health policy, the role of
      the nurse as consultant, and community-based care. After discussing the
      importance of health policy for graduate nursing education and reviewing the
      essentials of service learning, we describe a three-semester graduate sequence in
      health policy service learning. The focus is on the clinical and classroom
      components of both individual and group practica and their relationship to stages
      of nursing's political development. The article concludes with evaluation
      considerations and the implications of our work for nursing theory, research,
      practice, and education.

PMID- 11225049
TI  - Benchmarking best practices in Web-based nursing courses.
AB  - This article describes the framework and process to determine best practices in
      online learning communities for Web-based nursing courses. The benchmarks for
      best practices were determined based on evidence-based research in higher
      education. These quality indicators were then used to develop and pilot test a
      benchmarking survey across three state schools of nursing. The results of the
      pilot test, as well as the applications and implications for benchmarking best
      practices, are discussed.

PMID- 11225050
TI  - Narrative Pedagogy: Heideggerian hermeneutical analyses of lived experiences of
      students, teachers, and clinicians.
AB  - Research-based innovation in nursing education is needed to address complexities
      in both educational and clinical environments. This 12-year study describes
      Narrative Pedagogy that arises out of the common lived experiences of students,
      teachers, and clinicians in nursing education. Narrative Pedagogy as sharing and
      interpreting contemporary narratives is a call for students, teachers, and
      clinicians to gather and attend to community practices in ways that hold
      everything open and problematic. It utilizes conventional, phenomenologic,
      critical, and feminist pedagogies, along with postmodern discourses to revision
      nursing education. Narrative Pedagogy emanates out of interpretive phenomenology.
      The Concernful Practices of Schooling Learning Teaching are common experiences
      that belong together and co-occur and provide a new language for students and
      teachers. They will be explicated in the context of three narratives. Narrative
      Pedagogy is described as a research-based, innovative alternative for reforming
      nursing education.

PMID- 11225051
TI  - Creating a research base for nursing education: an interpretive review of
      conventional, critical, feminist, postmodern, and phenomenologic pedagogies.
AB  - The National League for Nursing Priorities for Nursing Education Research calls
      educators (1) to increase their pedagogic literacy to meet the challenges of the
      changing social, health care, and educational worlds and (2) to develop research
      based pedagogies for nursing. This interpretive review of conventional, critical,
      feminist, postmodern, and phenomenologic pedagogies facilitates the pedagogic
      literacy of faculty members and provides a background for research-based nursing
      education. An example of a research-based pedagogy, Narrative Pedagogy, which
      developed through interpretive (hermeneutic) studies of the lived experiences of
      students, teachers, and clinicians in nursing education, is explicated.

PMID- 11225052
TI  - Doctoral women as passionate scholars: an exploratory inquiry of passionate
      dissertation scholarship.
AB  - Advancement in knowledge development comes from novel perspectives and new
      visions, not from maintaining the status quo. Doctoral programs are mandated to
      develop nurse scholar-researchers who contribute to the discipline's body of
      knowledge. Although it stands to reason that doctoral students who are passionate
      about their dissertation research are more likely to make innovative
      contributions, there is little written about passionate scholarship in the
      nursing literature. This article describes an exploratory inquiry involving two
      focus groups of self-described passionate dissertation scholars. Underlining the
      passion, participants called passionate scholarship exciting and risky,
      personally meaningful and socially relevant life's work.

PMID- 11225053
TI  - Where is the nursing in nursing education?

PMID- 11225054
TI  - Sister chromatid exchange formation in mammalian cells is modulated by
      deoxyribonucleotide pool imbalance.
AB  - The formation of sister chromatid exchanges (SEC) is closely related to DNA
      replication which is dependent on the proper balance of deoxyribonucleic
      triphosphates. Since DNA precursor imbalances can influence DNA metabolism, the
      relationship between 5-bromodeoxyuridine (BrdUrd)-induction of SCE and nucleotide
      pool imbalance was examined in Syrian hamster fetal cells (HFC) and mouse 3T6
      cell line. In exponentially growing HFC, deoxyadenosine and deoxyguanosine
      stimulated the formation of SCE, while deoxycytidine (dCyd) prevented the dose
      dependent increase of SCE caused by BrdUrd. Cell growth inhibition produced by
      amino acid deprivation resulted in a significant increase in SCE as compared to
      exponentially growing cultures. This SCE enhancement was reduced by dCyd in HFC
      and did not occur in mouse 3T6 clone deficient in deoxycytidine deaminase. The
      modulation of SCE by DNA precursors is consistent with the induction of BrdUrd
      mutagenesis in mammalian cells and raises the possibility that common DNA changes
      are responsible for the induction of SCE and mutation in mammalian cells.

PMID- 11225055
TI  - Radiation hybrid mapping of human cytosolic malate dehydrogenase (hcMDH) to the
      short arm of chromosome 2.
AB  - Compartmentalization of human cytosolic malate dehydrogenase, hcMDH, together
      with its isozyme partner-mitochondrial form, hmMDH, plays an important role in
      the aerobic metabolism of the malate-aspartate shuttle and the citric acid cycle.
      However, they share few structural homology at the molecular level. The
      pseudogenes of mMDH has been reported in mice but hcMDH has no pseudogenes as
      shown by Southern blot analysis. A single band only was detected for the EcoRI
      digestion with 9.4 kb long of human genomic DNA and HindIII cutting with 2.8 kb
      long. hcMDH gene was mapped to chromosome 2 by somatic cell hybrid analysis and
      further localised to 268.72 cR from the top telomere of Chromosome 2 (near 2p15)
      by radiation hybrid mapping. The genes falling into this region may be related to
      dilated cardiomyopathy (DCM), several types of cancers and immunoregulation
      mechanism of cancers.

PMID- 11225056
TI  - Mutation inhibition by beta-estradiol after low doses of gamma-irradiation of
      mammalian cells.
AB  - The methodology previously described for measuring mutagenesis has been applied
      to the study of mutation prevention in immortalized G2 phase human lymphocytes
      exposed to 25 and 50 cGy of gamma-radiation. Caffeine prevents repair of
      mutations. Two times 10(-4) M beta-estradiol applied for 2.5 h markedly decreases
      induced mutations and affects male and female cells similarly. Quantitative
      measurement of mutagenesis in cells of different individuals and the effect of
      various agents on mutation yield should be important in prevention of cancer and
      other mutational disease.

PMID- 11225057
TI  - The mouse alanine:glyoxylate aminotransferase gene (Agxt1): cloning, expression,
      and mapping to chromosome 1.
AB  - The human alanine:glyoxylate aminotransferase gene (AGXT) has been cloned and
      characterized in detail, and various mutant alleles have been shown to be
      responsible for primary hyperoxaluria type 1 (PH1). However, advances in
      understanding the basic mechanisms of this rare human disease have been hampered
      by the lack of a suitable animal model. Although several AGXT homologous genes
      have been cloned in a number of mammalian species, none of them allows the level
      of genetic experimentation that current methods provide for mouse embryo
      manipulation. Thus, we have carried out the molecular cloning and analysis of the
      mouse Agxt1 gene, as a necessary first step towards the generation of a mouse
      model for PH1. The full-length mouse Agxt1 cDNA is 1545 bp long, and encodes a
      414 amino acid protein. Mouse Agxt1 is highly similar to its rat counterpart both
      at the nucleotide (91% identity) and the amino acid (92% identity) levels. Like
      its rat homologue, the larger mRNA species transcribed encodes a conserved amino
      terminal end characteristic of AGXT forms known to be targeted to the
      mitochondria. Mouse Agxt1 expression is restricted to the liver, and in vitro
      transfection of AGXT(-) cells with the cloned Agxt1 cDNA confers AGXT enzymatic
      activity. At the genomic level, mouse Agxt1 contains 11 exons, spanning 11 Kb,
      and it maps to the central portion of chromosome 1, a region of known synteny
      with human distal 2q, where AGXT has been previously mapped (2q36-37).

PMID- 11225058
TI  - Effects of sequence divergence on the efficiency of extrachromosomal
      recombination in mismatch repair proficient and deficient mammalian cell lines.
AB  - We have examined the effect of sequence divergence on the efficiency of
      recombination in mismatch repair proficient and deficient cell lines by using an
      exon-switch based assay that involves introns as recombination substrates.
      Sequence divergence of 15% decreased spontaneous recombination by six-fold in
      mismatch repair proficient cells but only three- and two-fold in human cells with
      defects in mismatch repair genes MLH1 and MSH2, respectively. The decrease in
      recombination efficiency in mismatch repair proficient background does not seem
      to be due to the production of rearranged recombination intermediates since these
      were readily detectable in the assay system we used. In contrast, the efficiency
      of double-strand break-induced recombination was not affected by sequence
      divergence in mismatch repair proficient or deficient background. These results
      indicate that sequence divergence and mismatch repair block initiation of
      spontaneous recombination but not recombinational repair of double-strand breaks.
      The differential sensitivity of these two processes may be required for genome
      stability.

PMID- 11225060
TI  - Chart pulling brought to its knees.

PMID- 11225059
TI  - Effects of homology length and donor vector arrangement on the efficiency of
      double-strand break-mediated recombination in human cells.
AB  - We use an Epstein-Barr virus (EBV) plasmid model chromosome system to study how
      different donor plasmid constructs affect recombination stimulated by an I-SceI
      induced double-strand break in the target sequence in human cells. The entire 3.5
      kb lacZ gene was efficiently recombined into a target EBV vector lacking lacZ
      sequences, but having limited homology to the donor plasmid. A donor plasmid with
      lacZ flanked by sequence homologous to the target consistently generated gene
      conversion events and was more effective than a donor carrying lacZ outside the
      same sequence homology. Reducing the length of homology between the target and
      donor from 5.5 kb to 1 kb caused only a 3-fold drop in recombination frequency,
      contrasting with the exponential dependence on homology length seen when no DSB
      is present in the target. These results document a DSB-induced 175-fold increase
      in recombination of a heterologous gene into a target, requiring only limited
      flanking homology.

PMID- 11225061
TI  - EMR to the rescue. An ambulatory care pilot project shows that data sharing
      equals cost shaving.
AB  - PROBLEM: Inefficiencies in managing office practices and costs. SOLUTION:
      Installation of an EMR in ambulatory practices to integrate clinical data from
      patient visits and use it to improve efficiencies "downstream". RESULTS: Marked
      reduction in costs of ambulatory practice management and major improvements in
      revenue capture, improved patient satisfaction. KEYS TO SUCCESS: Analysis of
      workflow, documentation of progress with benchmarking.

PMID- 11225062
TI  - Out with the paper, in with the mouse.

PMID- 11225063
TI  - New Zealand's health system Intranet fights for acceptance.

PMID- 11225064
TI  - A security strategy: possibly the biggest task on healthcare's to-do list.

PMID- 11225065
TI  - Wireless ... as technology improves, new applications take off.

PMID- 11225066
TI  - ASPs (application service providers) offer something that healthcare finds
      increasingly hard to get.

PMID- 11225068
TI  - Disease management ... technology that helps patients manage their chronic
      disease is proving its worth.

PMID- 11225067
TI  - Integration ... organizations streamline the business of healthcare by joining
      disparate systems.

PMID- 11225069
TI  - Workflow ... working software can streamline many administrative, financial and
      clinical tasks.

PMID- 11225071
TI  - Supply chain management ... Internet-based supply procurement is coming, but how
      to best exploit the technology is as yet unclear.

PMID- 11225070
TI  - Customer relationship management ... new applications promise the dual benefits
      of more revenues and healthier patients.

PMID- 11225072
TI  - Convergence ... integration of voice, video and data into one network offers
      benefits and challenges.

PMID- 11225073
TI  - Healthcare financing and delivery of the future. A look 10 years out uncovers
      scenarios ranging from divine to abysmal.

PMID- 11225074
TI  - Clinically oriented solutions in healthcare. Spending is likely to shift to
      clinical systems in 2001.

PMID- 11225075
TI  - Is this the year of the computer-based patient record?

PMID- 11225076
TI  - The crucial role of standards.

PMID- 11225077
TI  - The hidden insurance crisis.

PMID- 11225078
TI  - Act sharpens needlestick provisions.

PMID- 11225079
TI  - Give CNAs a career ladder to climb.

PMID- 11225080
TI  - A look at no-manual-lift programs.

PMID- 11225082
TI  - Sitting around, burning money.

PMID- 11225081
TI  - Is nothing sacred on the Net?

PMID- 11225083
TI  - OSHA stiffens its ergonomics stance.

PMID- 11225084
TI  - What's your next move on ergonomics?

PMID- 11225085
TI  - It's 2001: is your TPA (third-party administrator) ready?

PMID- 11225086
TI  - Getting to the heart of employee health.

PMID- 11225088
TI  - Data watch. Employers focus on Rx cost, not value.

PMID- 11225087
TI  - Gallup measures its own health.

PMID- 11225089
TI  - Folkman looks ahead. The controversial pioneer of angiogenesis is back on the map
      -and now his theories are being tested on humans.

PMID- 11225090
TI  - Soda pop that packs a punch. Are the new alcoholic lemonades aimed at kids?

PMID- 11225091
TI  - Solving the next genome puzzle. Identifying all our DNA was the easy part. Now,
      bring on the proteome.

PMID- 11225092
TI  - Plumbing planetary secrets. Scientists take aim at Earth's holy grail.

PMID- 11225093
TI  - AIDS is far from over. The disease is claiming new U.S. victims.

PMID- 11225094
TI  - Not built for the ages. We might not want to be 150 years old.

PMID- 11225095
TI  - Prescriptions: how your doctor makes the choice.

PMID- 11225096
TI  - The first nonlayered metal sulfonate structure: a 1-D Ba2+ network incorporating
      hydrophobic channels.

PMID- 11225097
TI  - Multicomponent polyanions. 57. Large-angle X-ray scattering study of aqueous
      molybdophenylphosphonate solutions.
AB  - The radial distribution functions are calculated from large-angle X-ray
      scattering (LAXS) measurements for one concentrated aqueous
      molybdate/heptamolybdate solution and five aqueous molybdophenylphosphonate
      solutions (lithium chloride medium). Besides water and hydrated lithium,
      chloride, and molybdate ions, five species in all, having different nuclearities,
      are postulated to exist in the solutions, according to equilibrium studies using
      potentiometry and 31P NMR spectroscopy. The structures of the three polymolybdate
      species Mo7O24(6-), Mo8O26(4-), and (C6H5P)2Mo5O21(4-), for which the structures
      are determined crystallographically, are confirmed to exist also in aqueous
      solution. The principal structures of the remaining two complexes,
      (C6H5P)Mo6O21(OH2)5(2-) and (C6H5P)Mo7O25(OH2)4-, are elucidated with the use of
      structures of related species. Both anions have one group of four edge-sharing
      MoO6 octahedra and another group of two MoO6 octahedra connected by sharing
      corners, forming a bent unsymmetric six-membered ring, with the C6H5PO3 group
      placed on the crowded side of the ring. In the former, the group of two MoO6
      octahedra is edge-shared, while in the latter, the group is face-shared,
      resulting in a ring small enough to tetrahedrally coordinate to the seventh
      molybdenum opposite the phenyl group.

PMID- 11225099
TI  - Separation of positional isomers of oxidation catalyst precursors.
AB  - A series of polypyridyl ruthenium complexes of the general formula
      [Ru(tpy)(bpy')Cl]+ where tpy is 2,2':6',2"-terpyridine and bpy' is 4-carboxy-4'
      methyl-2,2'-bipyridine (4-CO2H-4'-Mebpy), a proline derviative (4-CO-Pra
      (Boc)(OMe)-4'-Mebpy), or 4-((diethoxyphosphinyl)methyl)-4'-methyl-2,2'-bipyridine
      (4-CH2PO3Et2-4'-Mebpy) are prepared. For each complex, two isomers exist, and
      these are separated chromatographically. The structure of the hexafluorophosphate
      salt of cis-[Ru(tpy)(4-CO2H-4'-Mebpy)Cl]+, cis-1, is determined by X-ray
      crystallography. The salt crystallizes in the monoclinic space group Cc with a =
      12.4778(6) A, b = 12.6086(6) A, c = 20.1215(9) A, beta = 107.08200(1) degrees, Z
      = 4, R = 0.058, and Rw = 0.072. The structures of the remaining complexes are
      assigned by 1H NMR comparisons with cis-1. The complexes are potentially
      important precursors for the incorporation of RuIV=O2+ oxidants into polymers or
      peptides or for their adsorption onto oxide surfaces. Preliminary electrochemical
      results for the isomers of [Ru(tpy)(4-CH2PO3H2-4'-Mebpy)(H2O)]2+, 4, adsorbed on
      ITO (In2O3:Sn) surfaces add support to a recently proposed electron-transfer
      mechanism involving cross-surface proton-coupled electron transfer.

PMID- 11225098
TI  - Tmtacn, tacn, and triammine complexes of (eta 6-arene)OsII: syntheses,
      characterizations, and photosubstitution reactions (tmtacn = 1,4,7-trimethyl
      1,4,7-triazacyclononane; tacn = 1,4,7-triazacyclononane).
AB  - A series of (eta 6-arene)OsII complexes containing the saturated nitrogen donor
      ligands tmtacn, tacn, and NH3 are prepared and characterized. The electrochemical
      properties and photochemical reactions of these complexes are studied, and the
      solid-state structures for [(eta 6-p-cymene)Os(tacn)](PF6)2 (1) and [(eta 6-p
      cymene)Os(tmtacn)](PF6)2 (2) are determined. Single-crystal X-ray data: 1,
      orthorhombic, space group Pbca-D2h15 (No. 61), with a = 14.716(3) A, b =
      17.844(3) A, c = 18.350(4) A, V = 4819(2) A3, and Z = 8; 2, monoclinic, space
      group C2-C2(3) (No. 5), with a = 17.322(4) A, b = 10.481(3) A, c = 15.049(4) A,
      beta = 98.72 degrees, V = 2701(1) A3, and Z = 4.

PMID- 11225100
TI  - Hydrothermal synthesis of organic-inorganic hybrid materials: network structures
      of the bimetallic oxides [M(Hdpa)2V4O12] (M = Co, Ni, dpa = 4,4'-dipyridylamine).
AB  - The hydrothermal reactions of MCl(2).6H2O (M = Co, Ni) NaVO3, 4,4'-dipyridylamine
      (dpa), and H2O yield materials of the type [M(Hdpa)2V4O12] (M = Co (1), Ni (2)).
      The two-dimensional structures of 1 and 2 are constructed from bimetallic oxide
      networks (MV4O12)n2n- with monodentate Hdpa projecting the protonated ring into
      the interlamellar region. The oxide network may be described as ruffled chains of
      corner-sharing (VO4) tetrahedra linked by (NiO4N2) octahedra into the two
      dimensional assembly. Crystal data: C10H10Co0.5N3O6V2(1), monoclinic P2(1)/c, a =
      10.388(1) A, b = 7.6749(7) A, c = 16.702(2) A, beta = 102.516(1) degrees, Z = 4.
      C10H10N3Ni0.5O6V2 (2), monoclinic, P2(1)/c, c = 10.3815(2) A, b = 7.7044(2) A, c
      = 16.6638(4) A, beta = 102.573(1) degrees, Z = 4.

PMID- 11225101
TI  - Magnetic properties of diruthenium(II,III) carboxylate compounds with large zero
      field splitting and strong antiferromagnetic coupling.
AB  - The magnetic properties of mixed-valent compounds of general formula Ru2Cl(mu
      O2CR)4 [R = CH2-CH3 (1), C(Me)=CHEt) (2)] have been studied in the 2-300 K
      temperature range. This magnetic study also includes a revision of the magnetic
      properties of the complex Ru2Cl(mu-O2CCMePh2)4 (3). Compounds 1-3 show a linear
      structure and a strong antiferromagnetic coupling between the diruthenium units
      through the chlorine atoms according to previous studies. Two fitting models to
      explain the magnetic properties of these complexes that incorporate a large zero
      field splitting together with a strong antiferromagnetic coupling are described.
      These models consider that each diruthenium unit (S = 3/2) is magnetically
      coupled to the nearest diruthenium unit and ignores the longer distance magnetic
      coupling. The fitting models were found to be successful in fitting the magnetic
      data of the linear diruthenium(II,III) complexes. The zero-field splitting, D,
      and the antiferromagnetic coupling, zJ, vary from 37.8 to 48.0 cm-1 and from 
      7.43 to -13.30 cm-1, respectively, for complexes. The D values are similar to
      those calculated for the nonlinear diruthenium(II,III) compounds and confirm the
      validity of the proposed fitting models.

PMID- 11225102
TI  - Intramolecular rearrangements in six-coordinate ruthenium and iron dihydrides.
AB  - Molecular orbital calculations at the ab initio level are used to study polytopal
      rearrangements in H2Ru(PH3)4 and H2Fe(CO)4 as models of 18-electron, octahedral
      metal dihydrides. It is found that, in both cases, the transition state for these
      rearrangements is a dihydrogen species. For H2Fe(CO)4, this is a square pyramidal
      complex where the H2 ligand occupies an apical position and is rotated by 45
      degrees from its original orientation. This is precisely analogous to the
      transition state for Fe-olefin rotation in (olefin)Fe(CO)4 complexes and has a
      very similar electronic origin. Another transition state very close in energy is
      found wherein the basic coordination geometry is a trigonal bipyramid and the H2
      ligand is coordinated in the axial position. For H2Ru(PH3)4, the former
      stationary point lies at a much higher energy and the latter clearly serves as
      the transition state for hydride exchange. The reason for this difference is
      discussed along with the roles of electron correlation in the two compounds.

PMID- 11225103
TI  - Dicopper(I) complexes of unsymmetrical binucleating ligands and their dioxygen
      reactivities.
AB  - The design, synthesis, and characterization of binuclear copper(I) complexes and
      investigations of their dioxygen reactivities are of interest in understanding
      fundamental aspects of copper/O2 reactivity and in modeling copper enzyme active
      site chemistry. In the latter regard, unsymmetrical binuclear systems are of
      interest. Here, we describe the chemistry of new unsymmetrical binuclear copper
      complexes, starting with the binucleating ligand UN2-H, possessing a m-xylyl
      moiety linking a bis[2-(2-pyridyl)ethyl]amine (PY2) tridentate chelator and a 2
      [2-(methylamino)ethyl]pyridine bidentate group. Dicopper(I) complexes of UN2-H,
      [Cu2(UN2-H)]2+ (1), as PF6- and ClO4- salts, are synthesized. These react with O2
      (Cu:O2 = 2:1, manometry) resulting in the hydroxylation of the xylyl moiety,
      producing the phenoxohydroxodicopper(II) complex [Cu2(UN2-O-)(OH-)(CH3CN)]2+ (2).
      Compound 2(PF6)2 is characterized by X-ray crystallography, which reveals
      features similar to those of a structure described previously (Karlin, K. D.; et
      al. J. Am. Chem. Soc. 1984, 106, 2121-2128) for a symmetrical binucleating
      analogue having two tridentate PY2 moieties; here a CH3CN ligand replaces one
      pyridylethyl arm. Isotope labeling from a reaction of 1 using 18O2 shows that the
      ligand UN2-OH, extracted from 2, possesses an 18O-labeled phenol oxygen atom.
      Thus, the transformation 1 + O2-->2 represents a monooxygenase model system.
      [CuI2(UN2-OH)(CH3CN)]2+ (3), a new binuclear dicopper(I) complex with an
      unsymmetrical coordination environment is generated either by reduction of 2 with
      diphenylhydrazine or in reactions of cuprous salts with UN2-OH. Complex 3 reacts
      with O2 at -80 degrees C, producing the (mu-1,1-hydroperoxo)dicopper(II) complex
      [CuII2(UN2-O-)(OOH-)]2+ (4) (lambda max 390 nm (epsilon 4200 M-1 cm-1),
      formulated on the basis of the stoichiometry of O2 uptake by 3 (Cu:O2 = 2:1,
      manometry), its reaction with PPh3 giving O=PPh3 (85%), and comparison to
      previously studied close analogues. Discussions include the relevance and
      comparison to other copper bioinorganic chemistry.

PMID- 11225104
TI  - An extremely bent cyanide bridge in crystals of [(CN)3Pt(mu-CN)Cu(NH3)4].
      Influence of electrostatic forces on the nature and geometry of bridging cyanides
      in the solid state.
AB  - The dinuclear heterometallic complex [(CN)3Pt(mu-CN)Cu(NH3)4] has been obtained
      in the solid state, and its structure has been determined by X-ray diffraction
      techniques at two temperatures (102 and 233 K). C4H12CuN8Pt crystallizes in the
      orthorhombic system, with a = 14.554(3) A, b = 7.1901(12) A, c = 10.369(2) A, and
      V = 1085.1(3) A3 at 102 K (a = 14.5091(10) A, b = 7.2739(4) A, c = 10.4570(7) A,
      and V = 1103.61(12) A3 at 233 K), in space group Pnma, with Z = 4. The Pt and Cu
      atoms are linked by a CN bridge that presents a very bent C identical to N-Cu
      angle (120.1(6) degrees at 102 K). The C identical to N and N-Cu distances at 102
      K are 1.147(10) and 2.394(7) A, respectively. [(CN)3Pt(mu-CN)Cu(NH3)4] is
      embedded in an extensive electrostatic net formed by (N)H...N(C) interactions
      which, it is concluded, play an important role in the extreme deviation from
      linearity observed for the C identical to N-Cu angle.

PMID- 11225105
TI  - Cu(II)- and Hg(II)-induced modulation of the fluorescence behavior of a redox
      active sensor molecule.
AB  - Here, we report on a fluorescent 1,2,4-thiadiazole derivative (oxidized form) and
      its reduced form, the corresponding iminoyl thiourea. The thiadiazole displays a
      strong modulation of its fluorescence behavior, selectively upon addition of
      Cu(II), while the iminoyl thiourea functions as a chemodosimeter for Hg(II).
      Additionally, the Cu(II)-thiadiazole complex is characterized by HRMS, and the
      Hg(II)-induced desulfurization of the iminoyl thiourea is monitored by mass
      spectrometry.

PMID- 11225106
TI  - Electron distribution in the nonclassical bis(dithiolene) electron transfer
      series [M(CO)2(S2C2Me2)2]0/1-/2- (M = Mo, W): assessment by structural,
      spectroscopic, and density functional theory results.
AB  - The electron-transfer series [M(CO)2(S2C2Me2)2]0/1-/2- (series 2) have been
      established, and the previously reported series [M(S2C2Me2)3]0/1-/2- (series 3)
      confirmed, by voltammetry (M = Mo, W). Redox reactions are reversible with EMo >
      EW, and all members of each series have been isolated. Members of a given series
      have very similar distorted trigonal prismatic structures; isoelectronic
      complexes are isostructural. The existence of these series with structurally
      characterized members facilitates examination of geometric and electronic
      properties over three consecutive oxidation states. Upon traversing the series in
      the reducing direction, M-S, S-C, and C-O bond distances increase, and M-C,
      chelate ring C-C, and vCO values decrease. Density functional calculations
      identify the electroactive orbital, which is well separated in energy from other
      orbitals. Trends in bond lengths and vibrational frequencies in a given series
      are fully accountable in terms of increasing population of this orbital, whose
      composition is roughly constant across the series and is dominantly ligand (ca.
      80%) in character. Consequently, redox reactions in the two series are
      essentially ligand-based. The noninnocent nature of dithiolene ligands in
      oxidized complexes has been long recognized. The results of DFT calculations
      provide a contemporary description of the delocalized ground states in the two
      series. The trends in parameters involving the carbonyl groups provide a
      particularly clear indication of the classical behavior of a pi-acceptor ligand
      in isostructural molecules subject to consecutive reductions over three oxidation
      states.

PMID- 11225107
TI  - Syntheses, crystal structures, and magnetic properties of the oxalato-bridged
      mixed-valence complexes (FeII(bpm)3]2[FeIII2(ox)5].8H2O and
      FeII(bpm)3Na(H2O)2Fe(ox)(3).4H2O (bpm = 2,2'-bipyrimidine).
AB  - The preparation and crystal structures of two oxalato-bridged FeII-FeIII mixed
      valence compounds, [FeII(bpm)3]2[FeIII2(ox)5].8H2O (1) and
      FeII(bpm)3Na(H2O)2FeIII(ox)(3).4H2O (2) (bpm = 2,2'-bipyrimidine; ox = oxalate
      dianion) are reported here. Complex 1 crystallizes in the triclinic system, space
      group P1, with a = 10.998(2) A, b = 13.073(3) A, c = 13.308(3) A, alpha =
      101.95(2) degrees, beta = 109.20(2) degrees, gamma = 99.89(2) degrees, and Z = 1.
      Complex 2 crystallizes in the monoclinic system, space group P2(1)/c, with a =
      12.609(2) A, b = 19.670(5) A, c = 15.843(3) A, beta = 99.46(1) degrees, and Z =
      4. The structure of complex 1 consists of centrosymmetric oxalato-bridged
      dinuclear high-spin iron(III) [Fe2(ox)5]2- anions, tris-chelated low-spin
      iron(II) [Fe(bpm)3]2+ cations, and lattice water molecules. The iron atoms are
      hexacoordinated: six oxygen atoms (iron(III)) from two bidentate and one
      bisbidentate oxalato ligands and six nitrogen atoms (iron(II)) from three
      bidentate bpm groups. The Fe(III)-O(ox) and Fe(II)-N(bpm) bond distances vary in
      the ranges 1.967(3)-2.099(3) and 1.967(4)-1.995(3) A, respectively. The iron(III)
      iron(III) separation across the bridging oxalato is 5.449(2) A, whereas the
      shortest intermolecular iron(III)-iron(II) distance is 6.841(2) A. The structure
      of complex 2 consists of neutral heterotrinuclear Fe(bpm)2Na(H2O)2Fe(ox)3 units
      and water molecules of crystallization. The tris-chelated low-spin iron(II)
      ([Fe(bpm)3]2+) and high-spin iron(III) ([Fe(ox)3]3-) entities act as bidentate
      ligands (through two bpm-nitrogen and two oxalato-oxygen atoms, respectively)
      toward the univalent sodium cation, yielding the trinuclear (bpm)2Fe(II)-bpm
      Na(I)-ox-Fe(III)(ox)2 complex. Two cis-coordinated water molecules complete the
      distorted octahedral surrounding of the sodium atom. The ranges of the Fe(II)
      N(bpm) and Fe(III)-O(ox) bond distances [1.968(6)-1.993(5) and 1.992(6)-2.024(6)
      A, respectively] compare well with those observed in 1. The Na-N(bpm) bond
      lengths (2.548(7) and 2.677(7) A) are longer than those of Na-O(ox) (2.514(7) and
      2.380(7) A) and Na-O(water) (2.334(15) and 2.356(12) A). The intramolecular
      Fe(II)...Fe(III) separation is 6.763(2) A, whereas the shortest intermolecular
      Fe(II)...Fe(II) and Fe(III)...Fe(III) distances are 8.152(2) and 8.992(2) A,
      respectively. Magnetic susceptibility measurements in the temperature range 2.0
      290 K for 1 reveal that the high-spin iron(III) ions are antiferromagnetically
      coupled (J = -6.6 cm-1, the Hamiltonian being defined as H = -JS1.S2). The
      magnitude of the antiferromagnetic coupling through the bridging oxalato in the
      magneto-structurally characterized family of formula [M2(ox)5](2m-10)+ (M =
      Fe(III) (1), Cr(III), and Ni(II)) is analyzed and discussed by means of a simple
      orbital model.

PMID- 11225108
TI  - Synthesis, decomposition, and structural studies in the gas phase and solid state
      of N,N-dimethylaminoxygermane.
AB  - N,N-Dimethylaminoxygermane, H3GeONMe2, was prepared by the reaction of H3GeBr
      with LiONMe2 in dimethyl ether at -96 degrees C. The identity of H3GeONMe2 was
      proven by gas-phase IR and solution NMR spectroscopy (1H, 13C, 15N, 17O). It is
      an unstable volatile liquid compound. It decomposes by cleavage of a Ge-O and a
      Ge-H bond giving HONMe2 and an insoluble germanium hydride polymer (GeH2)n. This
      decomposition reaction has been modeled at the MP2/6-311G(d,p) level of theory by
      the homodesmotic reaction H3GeONMe2 + Ge2H6-->Ge3H8 + HONMe2, which is predicted
      slightly exothermic by 14 kJ mol-1. The molecular structure of H3GeONMe2 was
      determined by gas-phase electron diffraction supported by an ab initio geometry
      [MP2/6-311G(d,p)] and a force field [MP2/6-31G(d)]. The structure of the compound
      in the crystal lattice was determined by low-temperature crystallography using a
      single crystal of H3GeONMe2 grown in situ [C2H9NOGe, orthorhombic, Pnma, Z = 4, a
      = 8.1280(12) A, b = 9.7037(15) A, c = 7.0722(12) A]. Important bond lengths and
      angles (gas phase/solid state, A/deg) are Ge-O 1.785(2)/1.815(1), O-N
      1.462(7)/1.460(2), N-C 1.460(4)/1.453(2), Ge-O-N 105.2(5)/104.6(1), O-N-C
      105.8(5)/105.8(1), C-N-C 110.8(9)/111.2(2), Ge...N 2.587(6)/2.601(1). In the
      solid state the compound forms infinite chains by intermolecular Ge...O contacts
      of 2.808 A. The question of the attraction between Ge and N atoms is discussed
      with respect to reference Ge/O and N/O compounds, which have wider angles at
      oxygen than H3GeONMe2. For comparison the structures of the compounds H3CONMe2,
      H3SiONMe2, and H3SnONMe2 were also calculated to reflect the influence of the
      group 14 atom on the structure and to discuss the occurrence of weak E...N
      interactions in the compounds H3EONMe2.

PMID- 11225109
TI  - Synthesis and characterization of fluorinated tris(pyrazolyl)borate complexes.
      Observation of an (eta 5-pyrazole)-K+ interaction in the solid state.
AB  - Cyclopentadienyl (Cp) ligands have received considerable attention mainly because
      of their pi six-electron donation capability. Tris(pyrazolyl)borate ligands (Tp)
      are often compared with Cp because of their identical charge, number of donated
      electrons, and similar facial coordinating geometry. Their six-electron donation,
      however, is formally sigma-type. The X-ray structure of the [TpCF3,CH3CuK(mu 4
      CO3)KTpCF3,CH3]2 aggregate, 1, reveals for the first time an unprecedented eta 5
      TpCF3,CH3 potassium bonding interaction. 1 crystallizes in the triclinic space
      group P1 with a = 12.0411(2) A, b = 14.9791(2) A, c = 16.0567(3) A, alpha =
      71.301(1) degrees, beta = 69.785(1) degrees, gamma = 66.539(1) degrees, and Z =
      2. Both K-F and K-mu 4-CO3(2-) interactions stabilize the aggregate, as suggested
      by the lack of hexanuclear aggregation and K incorporation in the absence of
      fluorine groups or when O=CO2(2-) is replaced by CH3-CO2-. In the latter case we
      have isolated the complex [CuTpCF3,CH3(CH3CO2)], 2, which retains a Cu
      coordination sphere similar to that encountered in the TpCF3,CH3Cu subset of 1.
      The mononuclear complex 2 crystallizes in the monoclinic space group P2(1)/c with
      a = 14.1474(2) A, b = 14.1474(2) A, c = 19.0456(6) A, beta = 99.012(2) degrees,
      and Z = 4. The novel eta 5-coordination mode revealed in 1 suggests that Tp
      ligands might function not only as sigma donors but also as Cp-like pi donors.
      The eta 5-coordination mode might therefore constitute a new potential common
      denominator of these two important classes of ligands.

PMID- 11225110
TI  - Systematic structural coordination chemistry of p-tert
      butyltetrathiacalix[4]arene: 1. Group 1 elements and congeners.
AB  - Determinations of the crystal structures of complexes of the alkali metal ions
      with, in the case of Li, the dianion and, in the cases Na-Cs, the monoanion of p
      tert-butyltetrathiacalix[4]arene have shown that both the sulfur atoms which form
      part of the macrocyclic ring, as well as the pendent phenolic/phenoxide oxygen
      donor atoms, are involved in coordination to these metals. Although the Li and Na
      complex structures are similar to those of the corresponding complexes of p-tert
      butylcalix[4]arene, there is no similarity in the structures of the Cs complexes,
      with the present structure showing no evidence of polyhapto Cs(+)-pi
      interactions. Instead, the complex crystallizes as a ligand-bridged (S-, O-donor)
      aggregate of three Cs ions, solvent molecules, and four calixarenes, somewhat
      like the Rb complex, though here four Rb ions are present, and higher in
      aggregation than the K+ complex, where two K+ ions are sandwiched between two
      calixarene moieties. The triethylammonium complex of the thiacalixarene
      monoanion, though formally analogous in that it involves a monocation, has a
      simpler structure than any of the alkali metal derivatives, based formally on
      proton coordination (H-bonding). However, interestingly, it can be isolated in
      both solvated (dmf, dmso) and unsolvated forms, as indeed can the "free", p-tert
      butyltetrathiacalix[4]arene ligand itself.

PMID- 11225111
TI  - Electronic spectral studies of molybdenyl complexes. 2. MCD spectroscopy of
      [MoOS4]- centers.
AB  - Magnetic circular dichroism (MCD) and absorption spectroscopies have been used to
      probe the electronic structure of [PPh4][MoO(p-SC6H4X)4] (X = H, Cl, OMe) and
      [PPh4][MoO(edt)2] complexes (edt = ethane-1,2-dithiolate). The results of density
      functional calculations (DFT) on [MoO(SMe)4]- and [MoO(edt)2]- model complexes
      were used to provide a framework for the interpretation of the spectra. Our
      analysis shows that the lowest energy transitions in [MoVOS4] chromophores (S4 =
      sulfur donor ligand) result from S-->Mo charge transfer transitions from S
      valence orbitals that lie close to the ligand field manifold. The energies of
      these transitions are strongly dependent on the orientation of the S lone-pair
      orbitals with respect to the Mo atom that is determined by the geometry of the
      ligand backbone. Thus, the lowest energy transition in the MCD spectrum of
      [PPh4][MoO(p-SC6H4X)4] (X = H) occurs at 14,800 cm-1, while that in
      [PPh4][MoO(edt)2] occurs at 11,900 cm-1. The identification of three bands in the
      absorption spectrum of [PPh4][MoO(edt)2] arising from LMCT from S pseudo-sigma
      combinations to the singly occupied Mo 4d orbital in the xy plane suggests that
      there is considerable covalency in the ground-state electronic structures of
      [MoOS4] complexes. DFT calculations on [MoO(SMe)4]- reveal that the singly
      occupied HOMO is 53% Mo 4dxy and 35% S p for the equilibrium C4 geometry. For
      [MoO(edt)2]- the steric constraints imposed by the edt ligands result in the S pi
      orbitals being of similar energy to the Mo 4d manifold. Significant S pseudo
      sigma and pi donation may also weaken the Mo identical to O bond in [MoOS4]
      centers, a requirement for facile active site regeneration in the catalytic cycle
      of the DMSO reductases. The strong dependence of the energies of the bands in the
      absorption and MCD spectra of [PPh4][MoO(p-SC6H4X)4] (X = H, Cl, OMe) and
      [PPh4][MoO(edt)2] on the ligand geometry suggests that the structural features of
      the active sites of the DMSO reductases may result in an electronic structure
      that is optimized for facile oxygen atom transfer.

PMID- 11225112
TI  - Synthesis and redox characterization of the polyoxo anion, gamma*-[S2W18O62]4-: a
      unique fast oxidation pathway determines the characteristic reversible
      electrochemical behavior of polyoxometalate anions in acidic media.
AB  - The synthesis and characterization of (Bu4N)4[S2W18O62].1.23MeCN.0.27H2O are
      reported. It crystallizes in the monoclinic space group C2/c with a = 22.389(6)
      A, b = 22.104(3) A, c = 25.505(5) A, beta = 95.690(15) degrees, V = 12560(5) A3,
      and Z = 4. The anion exists as the gamma* isomer, the second example of this
      isomer type to be characterized structurally. The equivalent molybdenum salt
      occurs as the alpha isomer. gamma*-[S2W18O62]4- in MeCN solution displayed four
      electrochemically reversible one-electron redox processes at E1/2 values of 
      0.24, -0.62, -1.18, and -1.57 V versus the Fc+/Fc couple. Upon addition of acid
      in MeCN/H2O (95/5 v/v), the two most cathodic processes converted to an overall
      two-electron process at -0.71 V. The total data suggested that this process
      actually comprises two one-electron transfer processes, occurring at different
      potentials, with associated proton-transfer reactions. The interpretation is
      supported by simulation of the effect of acid titration upon the cyclic
      voltammetry. While multiple pathways for correlated reduction and protonation are
      present in both the molybdenum and tungsten systems, only a single fast oxidation
      pathway is available. As the reduced forms of [S2W18O62]4- are much weaker bases
      than those of [S2Mo18O62]4-, the individual oxidation pathways are not the same.
      However, their existence determines the highly reversible electrochemical
      behavior that is characteristic of these anions, and that of polyoxometalate
      systems in general.

PMID- 11225113
TI  - Construction of copper halide networks within layered perovskites. Syntheses and
      characterization of new low-temperature copper oxyhalides.
AB  - The construction of two-dimensional (2D) copper halide networks within a variety
      of perovskite hosts by a low-temperature topochemical method is demonstrated. Ion
      exchange between some layered perovskite oxides of the type A'[An - 1(M,M')nO3n +
      1] (A' = alkali metal, H, NH4; A = alkaline earth, rare earth, or Bi; M,M' = Nb,
      Ta, Ti; n = 2, 3) with CuX2 (X = Cl, Br) results in the oxyhalides (CuX)[An -
      1(M,M')nO3n + 1]. Rietveld refinements from X-ray powder diffraction data show
      that the structures of these new copper oxyhalides contain edge-sharing CuO2X4
      octahedra sandwiched between the M/M'O6 octahedra of the perovskite slabs. The
      compounds are low-temperature phases that decompose well below 700 degrees C. The
      copper oxyhalides exhibit antiferromagnetic ordering resulting from the magnetic
      exchange interactions within the planar Cu-X networks.

PMID- 11225114
TI  - Tungsten fluorides: syntheses and electrochemical characterization in the FLINAK
      molten salt eutectic.
AB  - The following tungsten fluorides have been synthesized by simple addition
      reactions or by reduction with tungsten metal at elevated temperature: KWF7,
      K2WF8, MWF6 (M = K, Na, Rb, Cs), K2WF7, M3WF8 (M = K, Na, Rb), and K3WF6. The
      compounds were characterized by their Raman spectra and by cyclic voltammetry in
      the molten FLINAK eutectic melt (46.5, 11.5, and 42.0 mol % of LiF, NaF, and KF,
      respectively) at 475-800 degrees C. X-ray crystal structures are reported for two
      new compounds K2WF7 and K3WF6. The crystals of K2WF7 were orthorhombic, space
      group Pnma (No. 62) with a = 9.800(2) A, b = 5.7360(11) A, c = 11.723(2) A, and Z
      = 4. Crystals of K3WF6 were cubic, space group Fm3 (No. 225) with a = b = c =
      8.9160(10) A, Z = 4. Electrodeposition of tungsten metal on Pt from FLINAK,
      prepared by the addition of WF6 gas and metallic tungsten to the melt, is
      suggested to result from reduction of an equilibrium mixture of WF8(3-) and WF6(3
      ).

PMID- 11225115
TI  - Hydrothermal synthesis and ab initio structural resolution from X-ray powder
      diffraction of a new open framework Cu(II) carboxyethylphosphonate: Na[Cu(O3P
      (CH2)2-CO2)].
AB  - Na[Cu(O3P-(CH2)2-CO2)], or MIL-39 (for Material of Institut Lavoisier), was
      synthesized hydrothermally at 443 K for 72 h under autogenous pressure. Its three
      dimensional open structure was determined from X-ray powder diffraction. MIL-39
      is monoclinic, it crystallizes in the space group P2(1)/m, (No. 11) with the
      following cell parameters at 293 K: a = 8.808(1) A, b = 6.4149(8) A, c =
      5.3418(8) A, beta = 105.75(1) degrees, Z = 2. Its framework contains double rows
      built from isolated distorted CuO5 square pyramids linked by PO3C tetrahedral
      groups from (O3P-(CH2)2-CO2)3- organic moieties. At the other end of these latter
      moieties, the carboxylate group links two different Cu polyhedra of two
      neighboring chains. These connections define two types of channels along [010].

PMID- 11225117
TI  - Specific recognition of chiral amino alcohols via lanthanide coordination
      chemistry: structural optimization of lanthanide tris(beta-diketonates) toward
      effective circular dichroism/fluorescence probing.
AB  - Lanthanide tris(beta-diketonates) formed stable, 1:1 highly coordinated complexes
      with amino alcohols, and the resulting complexes exhibited large enhanced
      fluorescence and intense induced circular dichroism (CD) signals. The stability
      constants of the highly coordinated complexes were determined for various
      combinations of lanthanide centers, beta-diketonate ligands, and organic
      substrates. These revealed that amino alcohol coordinated with the lanthanide
      center much more strongly than monoamine, monoalcohol, or diol derivative. On the
      basis of the highly coordinated complexation, several lanthanide tris(beta
      diketonates) acted as CD/fluorescence probes specific for amino alcohols.
      Tris(6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octadionato)europium(III) showed
      enhanced fluorescence in the presence of amino alcohols, while the corresponding
      ytterbium complex exhibited chirality-dependent CD signals for amino alcohols. In
      particular, the observed CD spectral profiles related well with the absolute
      configuration and optical purity of the bound amino alcohol, indicating that the
      structural optimization of lanthanide tris(beta-diketonates) offered specific
      sensing of amino alcohols and precise determination of their enantiomer excess
      percentages.

PMID- 11225116
TI  - Manganese(III) biliverdin IX dimethyl ester: a powerful catalytic scavenger of
      superoxide employing the Mn(III)/Mn(IV) redox couple.
AB  - A manganese(III) complex of biliverdin IX dimethyl ester, (MnIIIBVDME)2, was
      prepared and characterized by elemental analysis, UV/vis spectroscopy, cyclic
      voltammetry, chronocoulometry, electrospray mass spectrometry, freezing-point
      depression, magnetic susceptibility, and catalytic dismuting of superoxide anion
      (O2.-). In a dimeric conformation each trivalent manganese is bound to four
      pyrrolic nitrogens of one biliverdin dimethyl ester molecule and to the enolic
      oxygen of another molecule. This type of coordination stabilizes the +4 metal
      oxidation state, whereby the +3/+4 redox cycling of the manganese in aqueous
      medium was found to be at E1/2 = +0.45 V vs NHE. This potential allows the
      Mn(III)/Mn(IV) couple to efficiently catalyze the dismutation of O2.- with the
      catalytic rate constant of kcat = 5.0 x 10(7) M-1 s-1 (concentration calculated
      per manganese) obtained by cytochrome c assay at pH 7.8 and 25 degrees C. The
      fifth coordination site of the manganese is occupied by an enolic oxygen, which
      precludes binding of NO., thus enhancing the specificity of the metal center
      toward O2.-. For the same reason the (MnIIIBVDME)2 is resistant to attack by
      H2O2. The compound also proved to be an efficient SOD mimic in vivo, facilitating
      the aerobic growth of SOD-deficient Escherichia coli.

PMID- 11225118
TI  - Kinetics and mechanism of the oxidation of a substituted phenol by a
      superoxochromium(III) ion.
AB  - A superoxochromium(III) ion, CraqOO2+, abstracts the hydrogen atom from the
      hydroxylic group of a substituted, cationic phenol (ArOH), kCrOO = 1.24 M-1 s-1
      in acidic aqueous solution at 25 degrees C. The reaction has a large kinetic
      isotope effect, kArOH/kArOD approximately 12 and produces ArO., which also reacts
      with CraqOO2+ in a rapid second step, kArO = 1.26 x 10(4) M-1 s-1. The final
      oxidation product is an o-quinone, which was identified by its behavior on a
      cation-exchange resin, UV-visible spectrum, and reaction with iodide ions. This
      work has extended to three the types of element-hydrogen bonds that react with
      CraqOO2+ about 10(2) times more slowly than with CraqO2+. The mechanistic
      implications of these findings are discussed.

PMID- 11225119
TI  - Reaction of Ni2Cp2(mu-CO)2 with the alkylgallium(I) and alkylindium(I) compounds
      E4[C(SiMe3)3]4 (E = Ga, In). Insertion of E-R groups into the Ni-Ni bond versus
      replacement of CO by the isolobal E-R ligands.
AB  - The monomeric fragment In-C(SiMe3)3 was inserted into the Ni-Ni bond of Ni2Cp2(mu
      CO)2 upon treatment of the carbonyl complex with the tetraindium(I) compound
      In4[C(SiMe3)3]4, 1, in a molar ratio of 4 to 1. The product (3) contains an
      indium atom coordinated to one alkyl substituent and two Ni(Cp)CO groups in a
      planar coordination sphere. Reaction of the starting compounds in a molar ratio
      of 2 to 1 led to the replacement of both CO ligands by two InR groups. A compound
      (4) was formed that is isostructural to the carbonyl nickel complex and has a Ni2
      couple bridged by two InR ligands and two terminally coordinated cyclopentadienyl
      groups. The insertion product was not observed with the gallium derivative
      Ga4[C(SiMe3)3]4 (2); instead, a nickel gallium complex (5) analogous to 4
      containing two bridging GaR ligands was isolated as the only product regardless
      of the ratio of the starting compounds. On the basis of quantum chemical
      calculations, we conclude that there is no evidence for an In-In or Ga-Ga bond in
      complexes 4 or 5, respectively. This, however, supports a butterfly geometry,
      which is isostructural to the starting carbonyl complex Ni2Cp2(mu-CO)2.

PMID- 11225120
TI  - Synthesis and characterization of ruthenium(II) molecular assemblies for
      photosensitization of nanocrystalline TiO2: utilization of hydroxyl grafting
      mode.
AB  - New Ru polypyridine complexes [(bpy)2Ru(L)]2+, where bpy = 2,2'-bipyridine and L
      = dipyrido[3,2-a:2',3'-c]-phenazine-2-carboxylic acid (dppzc), dipyrido[3,2
      f:2',3'-h]quinoxaline-2,3-dicarboxylic acid (dpq(COOH)2), 3-hydroxydipyrido[3,2
      f:2',3'-h]quinoxaline-2-carboxylic acid (dpq(OHCOOH)), 2,3-dihydroxydipyrido[3,2
      f:2',3'-h]quinoxaline (dpq(OH)2), and [(L')Ru(dppzc)2]2+, where L' = bpy and 1,10
      phenanthroline (phen), have been synthesized, characterized, and anchored to
      nanocrystalline TiO2 electrodes for light to electrical energy conversion in
      regenerative photoelectrochemical cells with I-/I2 acetonitrile electrolyte.
      These sensitizers have intense metal-to-ligand charge-transfer (MLCT) bands
      centered at approximately 450 nm. The effect of pH on the absorption and emission
      spectra of these complexes consisting of protonatable ligands has been
      investigated in water by spectrophotometric titration. The excited-state pKa
      values are more basic than the ground-state ones, except the pKa2 and pKa2* in
      [(bpy)2Ru(dpq(OH)2)]2+, which are equal, suggesting the localization of the
      lowest-energy MLCT on heteroaromatic bridging ligands, dppzc and dpq. Incident
      photon-to-current conversion efficiency (IPCE) is sensitive to the structural
      changes that resulted from introducing different functional groups, used for
      grafting.

PMID- 11225121
TI  - Theoretical studies of biological nitrogen fixation. I. Density functional
      modeling of the Mo-site of the FeMo-cofactor.
AB  - The Mo-site and its ligand environment of the FeMo-cofactor (FeMo-co) were
      studied using the hybrid density functional method B3LYP. The structure and
      stability of the model complex (S-ligand)3(N-ligand)Mo[(S)-OCH(CH3)C(O)O-] along
      with its various protonated and reduced/oxidized forms were calculated. Several
      hypotheses were tested: (i) ligand environment of the Mo-site, (ii) monodentate
      vs bidentate coordination of the Mo-bound homocitrate ligand, (iii) substrate
      coordination to the Mo center, and (iv) Mo-His interaction. It was found that the
      decoordination of one of the homocitrate (lactate in the model) "legs", the
      bidentate-->monodentate rearrangement, does not occur spontaneously upon either
      single/double protonation or one-electron reduction. However, it could occur only
      upon substrate coordination to the Mo-center of the single-protonated forms of
      the complex. It was shown that one-electron reduction, single-protonation, and
      substrate coordination facilitate the bidentate<-->monodentate rearrangement of
      the homocitrate (lactate) ligand of FeMo-co. It was demonstrated that the
      smallest acceptable model of His ligand in FeMo-co is methylimidazolate (MeIm-).
      Our studies suggest that the epsilon-N of the FeMo-co-bound His residue is not
      protonated, and as a consequence the cluster is tightly bound to the protein
      matrix via a strong Mo-N delta bond.

PMID- 11225122
TI  - Solution chemistry of element 106: theoretical predictions of hydrolysis of group
      6 cations Mo, W, and Sg.
AB  - Fully relativistic molecular density-functional calculations of the electronic
      structure of hydrated and hydrolyzed complexes have been performed for the group
      6 elements Mo, W, and element 106, Sg. By use of the electronic density
      distribution data, relative values of the free energy changes and constants of
      hydrolysis reactions were defined. The results show hydrolysis of the cationic
      species with the formation of neutral molecules to decrease in the order Mo > W >
      Sg, which is in agreement with experiments for Mo, W, and Sg. For the further
      hydrolysis process with the formation of anionic species, the trend is reversed:
      Mo > Sg > W. A decisive energetic factor in the hydrolysis process proved to be a
      predominant electrostatic metal-ligand interaction.

PMID- 11225123
TI  - Structure of copper(II)-histidine based complexes in frozen aqueous solutions as
      determined from high-field pulsed electron nuclear double resonance.
AB  - W-band (95 GHz) pulsed EPR and electron-nuclear double resonance (ENDOR)
      spectroscopic techniques were used to determine the hyperfine couplings of
      different protons of Cu(II)-histidine complexes in frozen solutions. The results
      were then used to obtain the coordination mode of the tridentate histidine
      molecule and to serve as a reference for Cu(II)-histidine complexation in other,
      more complex systems. Cu(II) complexes with L-histidine and DL-histidine-alpha
      d,beta-d2 were prepared in H2O and in D2O, and orientation-selective W-band 1H
      and 2H pulsed ENDOR spectra of these complexes were recorded at 4.5 K. These
      measurements lead to the unambiguous assignment of the signals of the H alpha, H
      beta, imidazole H epsilon, and the exchangeable amino, Ham, protons. The 14N
      superhyperfine splitting observed in the X-band EPR spectrum and the presence of
      only one type of H alpha and H beta protons in the W-band ENDOR spectra show that
      the complex is a symmetric bis complex. Its g parallel is along the molecular
      symmetry axis, perpendicular to the equatorial plane that consists of four
      coordinated nitrogens in histamine-like coordinations (NNNN). Simulations of
      orientation-selective ENDOR spectra provided the principal components of the
      protons' hyperfine interaction and the orientation of their principal axes with
      respect to g parallel. From the anisotropic part of the hyperfine interaction of
      H alpha and H beta and applying the point-dipole approximation, a structural
      model was derived. An unexpectedly large isotropic hyperfine coupling, 10.9 MHz,
      was found for H alpha. In contrast, H alpha of the Cu(II)-1-methyl-histidine
      complex where only the amino nitrogen is coordinated, showed a much smaller
      coupling. Thus, the hyperfine coupling of H alpha can serve as a signature for a
      histamine coordination where both the amino and imino nitrogens of the same
      molecule bind to the Cu(II), forming a six-membered chelating ring. Unlike H
      alpha the hyperfine coupling of H epsilon is not as sensitive to the presence of
      a coordinated amino nitrogen of the same histidine molecule.

PMID- 11225124
TI  - Ancillary ligand effect on the properties of "Mg(thd)2" and crystal structures of
      [Mg(thd)2(ethylenediamine)]2, [Mg(thd)2(tmeda)], and [Mg(thd)2(trien)].
AB  - Complexes [Mg(thd)2(A)] (Hthd = 2,2,6,6-tetramethyl-3,5-heptanedione; A =
      ethylenediamine, en (2); N,N'-dimethylethylenediamine, dmeda (3); N,N'
      diethylethylenediamine, deeda (4); N,N,N',N'-tetramethylethylenediamine, tmeda
      (5); diethylenetriamine, dien (6); triethylenetetra-amine, trien (7); 1,2
      ethanediol (8)) and [Mg(thd)2(EtOH)]2(1,3-propanediol) (9) were prepared and
      characterized by NMR spectroscopy, mass spectrometry, and thermal analysis.
      Crystal structures of compounds 2, 5, and 7 are presented. In all structures, Mg
      exhibits distorted six-coordination, with four shorter distances between Mg and
      keto-oxygens and two longer distances between Mg and nitrogen atoms (2, 5, 7).
      The structure of 2 consists of two monomeric complexes which form an asymmetric
      unit. The structure of 7 is similar to 2, but the trien molecule has coordinated
      through one terminal and one vicinal N atom to Mg. All complexes containing
      amines evaporated almost completely, but the complex 8, which contained 1,2
      ethanediol, was thermally unstable and decomposed when heated. At temperatures
      below the dissociation temperature, all adducts of diamines appeared to evaporate
      intact.

PMID- 11225125
TI  - N,N'-dialkylimidazolium chloroplatinate(II), chloroplatinate(IV), and
      chloroiridate(IV) salts and an N-heterocyclic carbene complex of platinum(II):
      synthesis in ionic liquids and crystal structures.
AB  - The first imidazole-type carbene complex of platinum(II), cis-(C2H4)(1-ethyl-3
      methylimidazol-2-ylidene)PtCl2, has been obtained by reacting PtCl2 and PtCl4
      with ethylene in the basic [EMIM]Cl/AlCl3 (1.3:1) ionic liquid (where [EMIM]+ = 1
      ethyl-3-methylimidazolium) at 200 degrees C and structurally characterized
      (monoclinic P21/c space group, a = 10.416(2) A, b = 7.3421(9) A, c = 15.613(2) A,
      beta = 101.53(2) degrees, Z = 4). This complex can be regarded as a stable
      analogue of the pi-alkene-Pd(II)-carbene intermediate in the Heck reaction. In
      addition, a series of new N,N'-dialkylimidazolium salts of platinum group metals
      of the type [RMIM]2[MCln], where [RMIM+] = 1-alkyl-3-methylimidazolium and M =
      Pt(II), Pt(IV), or Ir(IV), have been prepared and characterized. The salts
      [EMIM]2[PtCl6] (1) and [EMIM]2[PtCl4] (2) were prepared in the ionic liquid
      [EMIM]Cl/AlCl3 and the salts [BMIM]2[PtCl4] (3) and [BMIM]2[PtCl6] (4) (where
      [BMIM]+ = 1-n-butyl-3-methylimidazolium) and [EMIM]2-[IrCl6] (5) in aqueous or
      acetonitrile media. From TGA measurements, salts 1-5 decompose in air in several
      steps eventually to form the corresponding metal, the onset of decomposition
      being observed at (degree C) 260 (1), 220 (2), 200 (3), 215 (4), and 210 (5). The
      structures of 1, 2, and 5 were determined by single-crystal X-ray analysis. The
      three salts crystallize in the monoclinic P21/n space group (1, a = 7.6433(9) A,
      b = 16.353(2) A, c = 9.213(1) A, beta = 113.56(1) degrees, Z = 2; 2, a = 8.601(1)
      A, b = 8.095(2) A, c = 13.977(2) A, beta = 91.75(2) degrees, Z = 2; 5, a =
      10.353(2) A, b = 9.759(2) A, c = 10.371(2) A, beta = 92.98(3) degrees, Z = 2).

PMID- 11225126
TI  - Surface modification of mesoporous, macroporous, and amorphous silica with
      catalytically active polyoxometalate clusters.
AB  - Transition-metal-substituted polyoxometalates (TMSP) of the type
      [MII(H2O)PW11O39]5- (M = Co, Zn) and [SiW9O37(CoII(H2O))3]10- have been
      chemically anchored to modified macroporous (400 nm pores), mesoporous (2.8 nm
      pores), and amorphous silica surfaces. The materials were characterized by solid
      state 31P MAS NMR, UV-vis, FT-IR spectroscopy, and N2 adsorption experiments to
      verify cluster attachment and the structure of the TMSP on the support. On the
      basis of the spectroscopic evidence, clusters were attached datively to the
      surface, and the integrity of the [CoPW11] cluster was maintained for nonaqueous
      impregnation with TBA5[CoPW11]; partial degradation of the cluster occurred when
      it was impregnated from aqueous solution using the K5[CoPW11] salt. Both the
      amine surface groups and the cobalt centers in the clusters were found to be
      necessary to prevent cluster loss during washing or reaction processes. The
      catalytic activities of the supported TMSP clusters were tested by the
      epoxidation of cyclohexene to cyclohexene oxide in the presence of
      isobutyraldehyde. The percent conversion of the substrate and the amount of
      product formed per unit time were similar for [CoPW11] clusters on each of the
      three silica supports, but slightly lower than for purely homogeneous reactions.
      [SiW9Co3] clusters with three available cobalt centers exhibited higher catalytic
      activity with nearly identical performance on a silica support or in homogeneous
      solution.

PMID- 11225127
TI  - Dimeric Cu(I) bromide species consisting of two edge-shared tetrahedra: crystal
      structure of (C8H14N2)2Cu2Br6.

PMID- 11225128
TI  - Transition assignments in the ultraviolet-visible absorption and magnetic
      circular dichroism spectra of phthalocyanines.

PMID- 11225129
TI  - Novel, trimeric Mn-substituted undecatungstosilicate, [(beta 2-SiW11MnO38OH)3]15
      .

PMID- 11225130
TI  - CuBi7I19(C4H8O3H)3(C4H8O3H2), a novel complex bismuth iodide containing one
      dimensional [CuBi5I19]3- chains.

PMID- 11225131
TI  - Titanium tert-butyl- and trimethylsilyl-imido complexes with monopendant arm
      triazacyclononane ligands.

PMID- 11225132
TI  - Secondary amyloidosis in chronic rheumatic diseases.

PMID- 11225133
TI  - Neuropathy in rheumatoid arthritis.
AB  - BACKGROUND: Paucity of Indian literature on rheumatoid neuropathy creates a
      lacuna in the critical evaluation and discussion of the subject. We did this
      study to find out the incidence and pattern of neuropathy and to correlate it
      with disease parameters and other extra-articular involvement. MATERIAL AND
      METHODS: We studied 31 patients of rheumatoid arthritis (RA) classified by ACR
      criteria. Electromyography and nerve conduction studies (EMG/NCV) were done in
      all the patients apart from routine laboratory and radiological investigations.
      Electrocardiograph (ECG), pulmonary function tests (PFT) and ophthalmological
      examination were also carried out to ascertain extra-articular involvement.
      RESULTS: Ten out of 31 RA patients had neuropathy of which five each were overt
      and subclinical respectively. Only one patient had entrapment neuropathy. Four of
      the ten patients had pure motor neuropathy whereas the other six were sensori
      motor neuropathies. Four patients had mononeuritis multiplex and five had
      symmetrical peripheral neuropathy. Nine of the ten neuropathic patients had RA
      for more than 2 years. Seven patients had other extra-articular features along
      with neuropathy. CONCLUSIONS: One-third of patients with RA have evidence of
      neuropathy. Disease parameters such as activity, rheumatoid factor and functional
      and radiological grade do not correlate with neuropathy. Non-entrapment sensori
      motor type of neuropathy is the most common type.

PMID- 11225134
TI  - Target gland functional status in patients with non-Cushing's pituitary
      macroadenomas undergoing transsphenoidal microsurgery.
AB  - OBJECTIVES: Hypopituitarism occurring in patients with pituitary macroadenoma may
      be reversible after pituitary microsurgery, and surgery itself can lead to
      hypopituitarism. This study was undertaken to evaluate target gland function
      prospectively in patients of non-Cushing's pituitary macroadenoma undergoing
      trans-sphenoidal microsurgery. MATERIAL AND METHODS: A prospective study of fifty
      patients of non-Cushing's pituitary adenoma was carried out to evaluate target
      gland (thyroid, adrenal and gonadal) undergoing trans-sphenoidal microsurgery.
      Thirty-two patients completed postoperative evaluation before radiotherapy.
      Target gland functions were assessed by measurement of T3, T4, TSH, basal and
      stimulated cortisol, LH, FSH, testosterone and estradiol. GH and PRL were also
      measured. Tumor size was assessed on CT/MRI scan. RESULTS: Hypothyroidism,
      hypoadrenalism and hypogonadism were present in 24%, 54% and 52% of patients.
      Preoperative hypopituitarism correlated with tumour size. Thyroid, adrenal and
      gonadal function improved in 87%, 50% and 31%; deteriorated in 4%, 29%, and 37%,
      respectively after trans-sphenoidal microsurgery. CONCLUSIONS: A subset of
      patients with non-Cushing's pituitary macroadenoma suffers from hypopituitarism,
      which reverses after surgery. Failure of recovery correlates with preoperative
      lower serum prolactin levels.

PMID- 11225135
TI  - Hyperfibrinogenemia in patients of diabetes mellitus in relation to glycemic
      control and urinary albumin excretion rate.
AB  - BACKGROUND: Diabetics have higher cardiovascular morbidity and mortality than
      general population and hyperfibrinogenemia is one of the important risk factors.
      MATERIAL AND METHODS: In the present study fibrinogen levels (dry clot weight
      method) were estimated in 50 diabetic subjects and 10 age, sex and body mass
      index matched controls and its correlation with various parameters like
      glycosylated hemoglobin (cation exchange resin method), urinary albumin excretion
      rate (Esbach's albuminometer), age, hypertension, body mass index (Kg/m2), lipid
      profile, smoking, duration of diabetes was studied. RESULTS: Higher plasma
      fibrinogen levels were found in diabetics (7.30 +/- 5.87 g/l) as compared to
      controls (4.06 +/- 2.5 g/l) which was statistically significant (p = 0.022).
      Fibrinogen levels were associated with age (r = 0.873), hypertension (p = 0.032),
      body mass index (r = 0.898), triglyceride level (r = 0.9396), cholesterol level
      (r = 0.99), glycosylated hemoglobin (r = 0.99) and urine albumin excretion rate
      (r = 0.930) in diabetics, in a significant manner. But, no correlation was found
      with sex (p > 0.05), family history (p = 0.072), duration of diabetes (r = 0.443)
      and smoking (p = 0.081). In controls positive correlation was found between
      fibrinogen level and age (r = 0.5), family history (p = 0.04), smoking (p =
      0.051), body mass index (r = 0.898) and lipid profile (r > 0.5). Mean albumin
      excretion rate was significantly (p = 0.002) higher in diabetics (397.42 +/-
      956.51 mg/min) and it was found to be associated with age (r > 0.5) and lipid
      profile (r > 0.5) in both diabetics and controls. No correlation was found
      between glycemic control and urine albumin excretion rate. CONCLUSION: Diabetics
      have higher fibrinogen levels, which is associated with glycemic control and
      urine albumin excretion rate in a statistically significant manner.

PMID- 11225136
TI  - Antioxidant and hypocholesterolaemic effects of Terminalia arjuna tree-bark
      powder: a randomised placebo-controlled trial.
AB  - OBJECTIVE: To evaluate the antioxidant and hypocholesterolaemic effects of
      Terminalia arjuna tree bark (a popular cardiotonic substance in Indian
      pharmacopoeia) and to compare it with a known antioxidant, vitamin E, we
      performed a randomized controlled trial. METHODS: One hundred and five successive
      patients with coronary heart disease (CHD) presenting to our centre were
      recruited and using a Latin-square design divided into 3 groups of 35 each. The
      groups were matched for age, lifestyle and dietary variables, clinical diagnosis
      and drug treatment status. None of the patients was on lipid-lowering drugs.
      Supplemental vitamins were stopped for one month before study began and American
      Heart Association Step II dietary advice was given to all. At baseline, total
      cholesterol, triglycerides, HDL and LDL cholesterol and lipid peroxide estimated
      as thiobarbituric acid reactive substances (TBARS) were determined. Group I
      received placebo capsules; Group II vitamin E capsules 400 units/day; and Group
      III received finely pulverized T. arjuna tree bark-powder (500 mg) in capsules
      daily. Lipids and lipid peroxide levels were determined at 30 days follow-up.
      RESULTS: Response rate in various groups varied from 86% to 91%. No significant
      changes in total, HDL, LDL cholesterol and triglycerides levels were seen in
      Groups I and II (paired t-test p > 0.05). In Group III there was a significant
      decrease in total cholesterol (-9.7 +/- 12.7%), and LDL cholesterol (-15.8 +/-
      25.6%) (paired t-test p < 0.01). Lipid peroxide levels decreased significantly in
      both the treatment groups (p < 0.01). This decrease was more in vitamin E group (
      36.4 +/- 17.7%) as compared to the T. arjuna group (-29.3 +/- 18.9%).
      CONCLUSIONS: Terminalia arjuna tree bark powder has significant antioxidant
      action that is comparable to vitamin E. In addition, it also has a significant
      hypocholesterolaemic effect.

PMID- 11225137
TI  - Effect of amifostine on toxicities associated with salvage combination
      chemotherapy.
AB  - PURPOSE: To determine the effect of amifostine on the safety and efficacy of
      chemotherapy in heavily pretreated patients and to study the side effects of
      amifostine delivered to patients receiving chemotherapy at a dose of 740 mg/m2.
      MATERIAL AND METHODS: Thirty-two patients of histologically proven (recurrent)
      malignancy who had previously received > or = 6 cycles of chemotherapy and
      developed grade II or grade III toxicities during treatment with salvage
      chemotherapy were eligible. These patients were given Injection Amifostine 740
      mg/m2 as a 15 min. i.v. infusion 30 min. prior to combination chemotherapy.
      RESULTS: A total of 85 cycles were administered with amifostine and 46 cycles
      without amifostine. The side effects during amifostine infusion were hypotension
      (9.6% cycles), vomiting (20% cycles), somnolence (33% cycles), sneezing (8%
      cycles), and flushing (19% cycles). The chemotherapy toxicities were reduced from
      47.7% to 30.6% for grade II and from 28% to 9.4% for grade III in case of
      gastrointestinal toxicity. Similarly there was improvement in the mean hemoglobin
      level from 8.2 gm% to 10.01 gm%, mean total leucocyte count from 2,280/mm3 to
      3,600/mm3. CONCLUSION: Amifostine has an excellent safety profile and is well
      tolerated by the patients. Pretreatment with Amifostine resulted in fewer
      treatment related delays and dose reduction resulting in better tolerance to
      salvage chemotherapy.

PMID- 11225138
TI  - Prevalence of rheumatic diseases in a rural population in western India: a WHO
      ILAR COPCORD Study.
AB  - BACKGROUND: COPCORD (Community oriented program from control of rheumatic
      diseases) is a global initiative of the WHO/International League of Associations
      from Rheumatology (ILAR). The prevalence data from the first Indian COPCORD
      survey (Stage 1), carried out in village Bhigwan (Dist. Pune), in 1996, is
      presented. AIM: To study the rural prevalence of rheumatic-musculoskeletal
      symptoms/diseases (RMSD). METHODS: A cross-sectional survey of the village (non
      randomised selection) was completed in five weeks, using validated
      questionnaires, served by 21 trained volunteers. 746 patients (18.2%, 95% CI: 17
      1-19-4) were identified (Phase 1) from 4092 adults (response 89%), and
      systematically evaluated (Phase 2 and 3) by a medical team, including a
      rheumatologist; limited investigations were carried out and diagnosis confirmed
      during a planned 12 week initial follow-up. Standard clinical criteria were used
      for the diagnosis; point prevalence estimates (prev)/confidence interval (CI) are
      shown in parenthesis. RESULTS: There was a dominant distribution of 'pain at all
      sites' (articular/soft tissues) in the females; painful neck (9.5%), back
      (17.3%), and calf (8.5%) appeared significant when compared to the Bhigwan males
      and the Indonesian and the Chinese rural COPCORD results. 55% RMSD were due to
      soft tissue rheumatism (5.5%) and an ill-defined/unclassifiable symptom-related
      diagnosis (7.1%). Osteoarthritis (5.8%) and inflammatory arthritis (IA) were seen
      in 29% and 10% patients respectively. 240 patients (5.9%) with chronic knee pains
      did not show any clinical evidence of OA. The prev of rheumatoid arthritis (0.5%,
      95% CI: 0.3-0.7), as classified by the American College of Rheumatology, was the
      highest ever reported from an Asian rural COPCORD study. Though unclassifiable IA
      (0.9%, 95% CI: 0.6-1.1) was seen, well defined reactive arthritis, TB, leprosy
      and connective tissue disorders were not observed. Gout was diagnosed in five
      patients (0.12%). CONCLUSIONS AND DISCUSSION: The Bhigwan COPCORD survey
      demonstrates a significant rural spectrum of RMSD. It provides a reasonable
      speculation about the Indian rheumatological burden. Further, an eight year
      prospective study is in progress to identify new cases and risk factors, and
      educate people (Stages 2 and 3).

PMID- 11225139
TI  - Intraocular pressure changes and mountaineering--preliminary observations and
      possible application.
AB  - Measurement of intraocular pressure (IOP) has been suggested as an indirect way
      of assessing the intra cranial pressure (ICP) because of the anatomical
      relationship between the brain and the eyeball. Mountain-sickness during high
      altitude climbing results from acute rise in ICP. In this preliminary study, we
      have observed gradual increase in IOP with gain in altitude in a group of healthy
      mountain trekkers. Although the rise in IOP had not been steep in most climbers
      who did not experience any significant symptoms, the rise had been steep into two
      subjects who experienced symptoms of acute mountain sickness with raised IOP.
      While clearly further work is needed in this field with larger number of
      subjects, measurement of IOP appears to be a useful non-invasive screening test
      in high altitude climbers to avert the risk of acute mountain sickness.

PMID- 11225140
TI  - Pictorial CME. Dystrophic myocardial calcification.

PMID- 11225142
TI  - All that is white is not milk.

PMID- 11225141
TI  - Methanol poisoning in medical intensive care unit.
AB  - A series of eight cases of methyl alcohol poisoning resulting from consumption of
      adulterated alcohol is presented. Most of the patients had blurring of vision
      followed by coma, metabolic acidosis and hemodynamic unstability (SBP < 90 mmHg)
      on admission to medical ICU. Early recognition and prompt initiation of treatment
      lead to successful recovery in five of these patients. Analysis of correlation
      between clinical and biochemical indicators of severity and indication for
      various therapeutic interventions are discussed.

PMID- 11225143
TI  - Rapid diagnostic tests for malaria.

PMID- 11225144
TI  - Pharmaceutical drug promotion: how it is being practiced in India?
AB  - The pharmaceutical industries (PI) throughout the World are heavily involved in
      aggressive drug promotions, with a clear aim to change the prescribing habits of
      physicians and to encourage the self-medication of patients. Broadly, drug
      promotion refers to all the informational and persuasive activities of the PI,
      the effect of which is to induce prescription, supply, purchase, and use of
      medicinal drugs. It includes the activities of medical representatives, drug
      advertisements to physicians, provision of gifts and samples, drug package
      inserts, direct-to-consumer advertisements, periodicals, telemarketing, holding
      of conferences, symposium and scientific meetings, sponsoring of medical
      education and conduct of promotional trials. The PI has the right to promote its
      products, but it should do so in a fair, accurate, and ethical manner. The
      promotional claims need to be reliable, truthful, informative, balanced, up-to
      date, and capable of substantiation in good taste. However, now a days, whilst
      the promotional methods have become very sophisticated and effective, it was
      found that while promoting their products, the PI does not adhere to these
      ethical principles. Hence, in most situations, these lead to irrational use of
      drugs. This unfortunate situation could be tackled only by the multiple prong
      strategy involving government, PI, doctors, medical associations and consumers.
      The government is required to formulate some guidelines in addition to developing
      their own code. The doctors and consumers are required to be educated on the
      promotional practices and abuses committed by the PI and different ways to tackle
      those. Various medical and consumer groups should also intervene to improve the
      scenario of promotion.

PMID- 11225145
TI  - Apolipoprotein deficiency and chronic liver disease.
AB  - Deficiency of apolipoprotein can be of genetic origin or due to diseases like
      advanced chronic liver disease. Deficiency of apolipoprotein A causes Tangier
      disease without any major hepatic involvement being reported. Deficiency of
      apolipoprotein B causes abetalipoproteinemia or familial hypobetalipoproteinemia;
      with hepatic involvement in the form of raised transaminases, fatty liver and
      cirrhosis. Advanced chronic liver disease itself can cause reduction of
      apolipoprotein A and apolipoprotein B levels and acanthocytosis. In patients with
      chronic liver disease of undetermined etiology, lipid profile and apolipoprotein
      levels should be obtained routinely. If it suggests apolipoprotein B deficiency,
      then liver biopsy can be avoided, as the etiology of chronic liver disease is
      established. Isolated deficiency of either apolipoprotein A or apolipoprotein B
      suggests etiology of chronic liver disease, while deficiency of both
      apolipoprotein A and apolipoprotein B is a manifestation of advanced chronic
      liver disease.

PMID- 11225146
TI  - Squamous cell carcinoma of thyroid gland.
AB  - We present the clinical manifestation, management and outcome in two cases of
      squamous cell cancer arising in the thyroid gland which is a rare entity. Both
      cases had advanced disease invading adjacent structures. At the followup of three
      to six months, one patient developed recurrence and died.

PMID- 11225147
TI  - Bronchioloalveolar carcinoma mimicking miliary tuberculosis.
AB  - A case of bronchioloalveolar carcinoma, with widespread dissemination to both
      lungs and miliary mottling on chest X-ray is reported in a 40 year old male.

PMID- 11225148
TI  - Primary papillary carcinoma in a thyroglossal cyst.
AB  - Papillary carcinoma arising in a thyroglossal cyst is rare. There is controversy
      regarding optimum management. We report a case managed by Sistrunk's procedure
      and external radiotherapy and review the literature on the subject.

PMID- 11225149
TI  - Fatty liver and elevated transaminases with heterozygous apolipoprotein B
      deficiency.
AB  - Asymptomatic fatty liver and elevated transaminases is a common occurrence with
      varied etiology. Apolipoprotein (apo) B deficiency is an uncommon cause of fatty
      liver and elevated transaminases. The typical lipid profile low cholesterol low
      LDL (low density lipoprotein) suggests diagnosis of apo B deficiency and an
      invasive procedure like liver biopsy can be avoided in such patients.

PMID- 11225150
TI  - Herpes zoster-induced myocarditis in a patient with diabetes mellitus.
AB  - Myocarditis as a complication of herpes zoster is very rare. I present the case
      of a middle-aged adult male with diabetes mellitus complicated by myocarditis
      following herpes zoster infection, the second reported case in Indian literature
      so far.

PMID- 11225151
TI  - Neurocysticercosis presenting as reversible parkinsonian syndrome.

PMID- 11225152
TI  - Tetralogy of Fallots co-existing with Marfan's syndrome--an uncommon association.

PMID- 11225153
TI  - Cardiac echinococcosis.

PMID- 11225154
TI  - Isolated idiopathic unilateral XIIth nerve palsy.

PMID- 11225155
TI  - An unusual case of spinal tuberculosis: role of MR study.

PMID- 11225156
TI  - Persistent fever in a case of typhoid--an unusual cause of neuroleptic malignant
      syndrome.

PMID- 11225157
TI  - Assessment of knowledge regarding metabolic control in diabetics.

PMID- 11225158
TI  - Relationship between osteoarthritis of knee and menopause.

PMID- 11225159
TI  - Hazards of HBV infection following child adoption.

PMID- 11225160
TI  - Pyomyositis: an underdiagnosed entity.

PMID- 11225161
TI  - Patients' adherence to diabetes treatment.

PMID- 11225162
TI  - Immunomodulators in acute prolonged hepatitis.

PMID- 11225163
TI  - HCFA finalizes rule on Medicare coverage of outpatient diabetes self-management
      training.

PMID- 11225164
TI  - FDA approves nateglinide for treatment of type 2 diabetes.

PMID- 11225166
TI  - Lysine for management of herpes labialis.

PMID- 11225165
TI  - Antiretroviral combination may put pregnant women at risk of fatal lactic
      acidosis.

PMID- 11225167
TI  - Treatment of Crohn's disease with infliximab.
AB  - The role of infliximab in managing Crohn's disease (CD) is described. CD is
      characterized by chronic transmural inflammation at various sites of the
      gastrointestinal tract, particularly the ileum and colon. The major symptoms are
      diarrhea, abdominal pain, enterocutaneous and perianal fistulas, and weight loss.
      Management goals include alleviating symptoms, inducing remission, promoting
      healing of the intestinal mucosa and fistulas, and modifying the disease process.
      Drugs traditionally used to manage CD are aminosalicylates, antimicrobials,
      immunomodulatory agents, and corticosteroids. Infliximab is a chimeric (human
      mouse) monoclonal antibody targeted at human tumor necrosis factor-alpha (TNF
      alpha), a proinflammatory cytokine important in the pathogenesis of CD.
      Infliximab antagonizes the biological activity of TNF-alpha by binding to it on
      macrophage and T-cell surfaces. Clinical trials have shown infliximab to be
      effective in producing and maintaining a clinical response in patients with
      refractory, moderate to severe CD. Treatment helps promote healing of intestinal
      mucosa and closure of fistulas. Infliximab may act more rapidly than most
      traditional agents and produces less severe adverse effects. The most frequent
      adverse effects are headache, nausea, and upper-respiratory-tract infections. The
      recommended dosage is 5 mg/kg i.v. infused over a two-hour period. Infliximab may
      be given at eight-week intervals for maintenance or management of flare-ups.
      Infliximab appears useful in the treatment of CD and may improve patients'
      quality of life.

PMID- 11225168
TI  - Validity of home blood glucose reporting by geriatric patients.

PMID- 11225169
TI  - Patient satisfaction with a scheduled prescription-refill service.

PMID- 11225170
TI  - Goal attainment and maintenance of serum cholesterol level in a pharmacist
      coordinated lipid clinic.

PMID- 11225171
TI  - ASHP therapeutic position statement on the identification and treatment of
      Helicobacter pylori-associated peptic ulcer disease in adults. Developed by the
      ASHP Commission on Therapeutics and approved by the ASHP Board of Directors on
      November 11, 2000.
AB  - ASHP supports the identification and treatment of H. pylori infection in
      appropriate patients as an effective method of reducing the morbidity and
      mortality associated with peptic ulcer disease. Successful and safe therapy
      requires extensive patient education and monitoring by qualified health care
      professionals to maximize patient understanding of and compliance with medication
      regimens and to minimize adverse events. Pharmacists are key to ensuring that
      patients use prescribed regimens appropriately so that H. pylori is eradicated
      and that clinical outcomes of associated peptic ulcer disease are optimal.

PMID- 11225172
TI  - [Deciding factor plausibility].

PMID- 11225173
TI  - Microbiological quality of fresh leafy vegetables, salad components and ready-to
      eat salads: an evidence of inhibition of Listeria monocytogenes in tomatoes.
AB  - A total of 116 samples of 11 different fresh vegetables from a local market
      generally consumed in raw form as well as 12 samples of ready-to-eat green salads
      procured from three grade 1 and 2 restaurants in Mumbai, India were examined for
      overall microbial quality in terms of bacterial, mold and coliform levels and
      incidence of pathogens such as Listeria and Yersinia. Standard procedures and
      media were used for isolation and identification studies. Thoroughly washed
      samples of 26 leafy vegetables, 12 roots, 62 tomatoes and four samples each of
      cabbage, capsicum and cucumber showed total bacterial and yeast-mold count in
      10(6)-10(7) cfu/gm and 10(2)-10(5) cfu/gm range respectively. On the other hand,
      higher range of bacterial (10(6)-10(8) cfu/gm) and mold (10(4)-10(7) cfu/gm)
      count were noticed in ready-to-eat salads from restaurants. The MPN index/gm for
      coliforms for vegetables from a local market ranged from < 3 to > 1100 whereas
      for ready-to-eat salads it was 11 to 460. Evidence of higher number of coliforms
      was observed mostly in green leafy vegetables. All (100%) local vegetables
      exhibited the incidence of Listeria and Yersinia. On the other hand, ready-to-eat
      salads showed 20 and 73% presence of Yersinia and Listeria respectively. Higher
      occurrence of fecal coliforms was (65.6%) found in raw vegetables while they were
      absent in ready-to-eat salad samples. Non-pathogenic species like Y. intermedia
      and L. innocua were predominating species in most of the samples. Nevertheless,
      presence of L. monocytogenes was observed in 7 out of 62 tomatoes, 5 out of 10
      coriander leaves, 2 out of 4 spinach samples and one from 4 cabbage samples.
      Studies conducted to understand the ability of L. monocytogenes 036 and 35152 to
      grow in tomato in the presence of naturally occurring bacteria suggested that
      artificially inoculated (10(3) cfu/ml) cells are killed after 3 days, 12 days and
      14 days of incubation at 37 degrees C, 8-10 degrees C and 2-4 degrees C
      respectively.

PMID- 11225174
TI  - Comparison of the protein nutritional value of food blends based on sorghum,
      bambara groundnut and sweet potatoes.
AB  - The protein quality of four blends based on sprouted sorghum, bambara groundnuts
      and fermented sweet potatoes had been evaluated by rat feeding experiments;
      casein served as a reference protein. The test proteins were incorporated to make
      up 1.6% total nitrogen. There was an inverse relationship between % nitrogen
      disgestibility and the proportion of sorghum protein in the blend; being highest
      (89.7%) in the diets based on sorghum:bambara groundnut:sweet potatoes with
      protein ratios of 52:46:2. This blend proved to be optimum when the biological
      value (93.6%) and the net protein utilization (84%) were used as protein indices.
      The findings imply that foods with good protein quality could be formulated from
      a blend of sorghum-bambara groundnut and sweet potatoes, provided appropriate
      processing and blending are taken into consideration.

PMID- 11225176
TI  - Selenium levels in cow's milk from different regions of Australia.
AB  - Homogenised cow's milk samples were collected each season in 1990 and 1991 from
      19 selected dairy factories in different regions across Australia. Fresh cow's
      milk samples were also collected every month in 1990 and 1991 from 24 selected
      dairy farms in Queensland. Selenium (Se) analyses were performed by
      spectrofluorimetry after complexing with 2,3-diaminonaphthalene. The study found
      a wide variation of Se levels in homogenised milk from dairy milk factories.
      Statistical analysis using unpaired t-test showed that Se levels in summer were
      significantly higher (P < 0.001) than in other seasons. Mean concentrations in
      summer, autumn, winter and spring for 1990 and 1991 were 23.8 +/- 4.6, 20.9 +/-
      4.4, 20.7 +/- 4.2 and 20.6 +/- 4.8 micrograms/L, respectively. A two-way ANOVA
      analysis also indicated that regions and season have a significant influence (P <
      0.001) on Se levels and that there is an interaction between regions and seasons.
      High Se levels in each region tend to be associated with high Se levels in summer
      milk. A wide variation of Se levels was also found in raw milk collected from
      dairy farms. Mean concentration was 22.0 +/- 6.0 micrograms/L, with a range of
      6.7 to 47.6 micrograms/L. When the values of Se levels in homogenised milk for
      each season were used to estimate the contribution of milk to daily intake of
      different populations groups, it was found that infants have the highest intake
      (10.0-12.2 micrograms/day) which meets the Australian Recommended Dietary Intake.

PMID- 11225175
TI  - Evaluation of soybean oil quality during conventional frying by FTIR and some
      chemical indexes.
AB  - Conventional deep fat frying is a common food preparation technique in Mauritius.
      The deterioration of soybean oil, commonly used in conventional frying, has been
      studied during frying of potato chips. The oil was subjected to continuous frying
      at 180 degrees C for a total of 600 min. The quality changes in soybean oil were
      evaluated at 90 min interval by Fourier transform infrared (FTIR) spectroscopy
      and some routine chemical parameters, namely peroxide value, iodine value and
      free fatty acid. An increase in hydroperoxide and free fatty acid concentration
      has been observed during the frying process by FTIR technique and the chemical
      parameters, peroxide value and free fatty acid respectively. A significant
      decrease in triglyceride ester linkage was observed by FTIR. The linear decrease
      noted for iodine value (P < 0.01) indicated a general loss of unsaturation.
      Furthermore, FTIR studies showed a loss of cis double bonds along with an
      increase in trans unsaturation. The formation of unsaturated aldehyde has also
      been observed during the frying process by FTIR technique.

PMID- 11225177
TI  - Some microbiological and biochemical studies on the fermentation of 'awaze' and
      'datta', traditional Ethiopian condiments.
AB  - The microbial and some biochemical changes during the fermentation of two
      Ethiopian condiments were studied. The aerobic mesophilic microflora of the
      ingredients of 'awaze' were dominated by Bacillus species (1.1 x 10(6) cfu/g) and
      lactic acid bacteria (4.5 x 10(4) cfu/g). The counts of aerobic mesophilic
      bacteria declined during the fermentation period. Lactic acid bacteria (LAB)
      reached the maximum count of 5.9 x 10(9) cfu/g at day 4 and the count remained >
      10(8) cfu/g throughout the fermentation. The heterofermentative LAB dominated
      until day 3; thereafter the homolactics dominated the fermentation. Yeasts
      appeared at day 6 and increased to 2.5 x 10(6) cfu/g. In 'datta' fermentation,
      the count of aerobic mesophilic bacteria remained unchanged during the
      fermentation. LAB initiated the fermentation at a level of 7.1 x 10(4) cfu/g and
      reached 1.2 x 10(9) cfu/g at day 7. The homolactic LAB initiated and dominated
      the fermentation for the first 2 days and the heterolactics took over thereafter.
      Both fermentations were accompanied by declining pH and increasing titratable
      acidity. Salmonella typhimurium was inhibited during both fermentations within 48
      h. Both 'awaze' and 'datta' had low initial contents of available protein and
      reducing sugars and these did not show marked differences throughout the
      fermentation.

PMID- 11225178
TI  - Saponin content and trypsin inhibitor activity in processed and cooked pigeon pea
      cultivars.
AB  - Four high-yielding varieties of pigeon pea namely UPAS-120, Manak, JCPL-151. ICPL
      87 had considerable amounts of antinutrients i.e. saponins and trypsin
      inhibitors. Saponin content of these unprocessed cultivars ranged from 2164 to
      3494 mg/100 g. There were significant varietal variations in trypsin inhibitor
      activity (1007-1082 TIU/g) of these pigeon pea cultivars. Some simple,
      inexpensive and easy-to-use domestic processing and cooking methods, namely,
      soaking (6, 12, 18 h), soaking (12 h)-dehulling, ordinary cooking, pressure
      cooking and germination (24, 36, 48 h) were found to be quite effective in
      lowering the level of saponins and trypsin inhibitors in all the pigeon pea
      cultivars. Pressure cooking of soaked and dehulled seeds lowered the content of
      saponins to a maximum extent (28 to 38%) followed by ordinary cooking of soaked
      and dehulled seeds (28 to 35%), soaked dehulled raw seeds (22 to 27%) and 48 h
      germinated seeds (15 to 19%). Loss of TIA was marginal due to soaking but
      ordinary as well as pressure cooking of unsoaked and soaked-dehulled pigeon pea
      seeds reduced the TIA drastically. Pressure cooking of pigeon pea seeds
      completely destroyed the TIA while it was reduced to the extent of 86-88% against
      the control in 48 h pigeon pea sprouts.

PMID- 11225179
TI  - Health benefits of dietary fat reduction by a novel fat replacer: Mimix.
AB  - The primary goals of this study were to identify any health benefits of the
      replacement of dietary fat with a novel fat replacer, Mimix, and to assure that
      the consumption of this fat replacer did not convey any deleterious health
      effects. Male, weanling, Fischer 344 rats were fed one of six diets containing
      between 5 and 20% w/w as fat for 8 weeks. These diets included two high fat diets
      (safflower oil or lard), a low fat diet and three diets where 15% of the fat in
      the high fat diets was replaced with various amounts of Mimix. When animals were
      fed a diet rich in saturated fat they consumed significantly more energy than
      other diet groups. When 15% saturated fat (lard) was replaced with safflower oil
      animals adjusted their food intake so that no difference in energy intake was
      observed between the high safflower diet and the low fat and Mimix diets. When
      the various Mimix fat replacements were compared to animals fed a high fat lard
      diet there was incomplete compensation of energy intake. Animals fed the high fat
      lard diet also had higher glucose and total serum cholesterol than their low fat
      and fat replacement counterparts. Feeding a high fat safflower oil diet to rats
      resulted in a significantly lower total serum cholesterol and serum triglyceride
      than all other diets. Replacement of dietary fat with Mimix demonstrated no
      deleterious effects on the heart, liver and intestinal tract that were all of
      normal weight, morphology and colour compared to other diet groups. Body
      composition analysis demonstrated that animals fed high fat diets had higher body
      fat mass at the expense of lean body mass. This was most obvious for animals fed
      high fat lard diets who had heavier epididymal fat pads. These data demonstrate
      that the replacement of dietary fat with the novel fat replacer Mimix can convey
      a number of health benefits in the absence of any deleterious effects.

PMID- 11225180
TI  - Nutritional evaluation of some processed catering foods.
AB  - Five prepared catering dishes were analysed to evaluate the proximate composition
      and the fatty acids, vitamin E, thiamine and riboflavin content. The
      correspondent values were calculated from actually available food composition
      tables (two from Italy, one from the UK and one from the USA). When using more
      than one database to calculate the composition of a complex recipe the average
      values were similar to the analytical ones despite the wide range reported for
      some variables. However, there was no significant difference in the statistical
      analyses between the analytical values and databases, or among the databases
      themselves. Therefore if the composition of a specific recipe is required,
      analyses would be advisable, but the available databases are quite adequate if
      the evaluation is for groups of people, even allowing for the seasonal
      variability of ingredients.

PMID- 11225181
TI  - Some nutritional properties of the seeds of three Mucuna species.
AB  - The seeds of Mucuna nivea, M. pruriens and M. utilis showed ash 4.3-5.1%, oil 4.9
      5.5%, protein 25.9-27.5%, L-dopa 3.6-4.2%, trypsin 28.5-39.7 mg/g and
      chymotrypsin inhibitor activity 19.3-24.6 mg/g. The trypsin and chymotrypsin
      inhibitor activity increased in pod hull and seeds while the amount of protein
      increased in seeds and decreased in pod hull with maturity. The essential amino
      acid profile was comparable to the FAO pattern (lysine 6.0-6.4%). The fatty acid
      composition had total unsaturated acids 51.9-55.9%, but were poor in oil
      contents.

PMID- 11225183
TI  - Chemical, physical and sensory properties of chicken frankfurters substituted
      with palm fats.
AB  - Physico-chemical and sensory characteristics of frankfurters prepared with three
      types of palm fats (PF60: 40, PF70: 30 and PF80: 20) and palm olein (POo) at 20
      and 25% of fat levels were studied. Incorporation of different fats at 20 and 25%
      did not affect the cooking yields of the frankfurters. Frankfurters incorporated
      with 25% POo showed the highest value of water-holding capacity (WHC) among eight
      formulations. The frankfurters containing POo showed the least cooking loss
      compared to those with palm fats. The incorporation of different type and level
      of fats resulted in significant changes in the colour (lightness, redness,
      yellowness) of frankfurters. Texture profiles of both raw and cooked frankfurters
      were found to be altered by the blending of different type and level of fats. In
      raw frankfurters, hardness for frankfurters mixed with palm fats were
      significantly higher than the one with POo but greater values for cohesiveness
      was observed in raw frankfurters blended with POo. Lowest chewiness was
      demonstrated by frankfurters mixed with 20% POo. Grilling increased the hardness
      values of all frankfurters. Contrary to the raw counterparts, cooked frankfurter
      with POo was the hardest among all formulations. Cohesiveness and chewiness was
      also found to be significantly higher for cooked frankfurters mixed with POo. Raw
      frankfurters with fat content of 25% showed greater value in hardness than those
      of 20%. However, there were no significant differences (P > 0.05) observed for
      all the texture profile attributes in cooked frankfurters due to fat levels. In
      sensory evaluation, frankfurters prepared with POo were found to be most
      acceptable by consumer panels as they scored the highest for hardness rating,
      chicken flavour, oiliness and overall acceptance attributes.

PMID- 11225182
TI  - Acceptability of extrusion cooked cereal/legume weaning food supplements to
      Ghanaian mothers.
AB  - Six cereal/legume mixtures were developed with the aid of computer-assisted
      optimization software from cereal and legume staples indigenous to the West
      African sub-region. The mixtures had 45-50% maize, 35-40% decorticated cowpeas
      and either blanched peanuts or decorticated soybeans as a source of lipid and
      complementary amino acids. Three processing schemes involving roasting, amylase
      digestion and extrusion cooking were employed. The proportion of ingredients in
      each cereal/legume blend was based on meeting the nutrient requirement of the 0.5
      0.9-year-old infant and cost considerations. Nutrient composition of the blends
      (proximate, amino acid, mineral and vitamin composition) indicated that these
      formulations were adequate nutritionally as weaning supplements (Mensa-Wilmot et
      al, 2000a,2000b). These formulations were evaluated by mothers of weanling
      children based on their preferences with respect to color, flavor, texture and
      willingness to purchase the product assessed. A total of 133 one-on-one
      interviews and 23 group discussions were conducted (involving 6-12 respondents)
      with selected Ghanaian women. The mothers found the convenience of a weaning food
      made from local staples that could be processed on village/market scale very
      attractive.

PMID- 11225184
TI  - Grammatical style of nutrition education messages.
AB  - Nutrition education messages were written about eight different foods or food
      products in eight different styles. Styles were suggestions, instructions using
      'should', rhetorical questions using 'how about' or 'why not', statements of
      fact, positive commands, positive commands followed by negative commands or vice
      versa. Subjects (n 160) rated messages for persuasiveness and also stated how
      often they already complied with each message. Scores were adjusted to remove the
      contributions related to sex, age group, social class, reported compliance and
      food about which the message had been written. The main factor influencing score
      for persuasiveness was the extent to which subjects claimed to be already
      complying with the messages. There were no significant effects of the method of
      construction of messages on score using one-way analysis of variance.

PMID- 11225185
TI  - Are you putting patients in danger? You need to reduce your diversion rates.
AB  - High diversion rates are a crisis nationwide, with many EDs reporting high
      diversion rates throughout the year that cause potentially unsafe conditions for
      patients. To avoid diversion, length of stay must be reduced not only in the ED,
      but hospitalwide. Patients will continue to come to the ED during diversion, so
      be prepared. Have an effective diversion policy and an expeditious process to
      implement it when needed.

PMID- 11225187
TI  - Reduce 'boarder' patients in your department.

PMID- 11225186
TI  - Avoid diversion by looking outside of your ED.

PMID- 11225188
TI  - How to communicate your diversion message.

PMID- 11225189
TI  - Point/counterpoint. ED managers: do not stop restocking.

PMID- 11225190
TI  - Point/counterpoint. EDs should not be resupplying.

PMID- 11225191
TI  - Detection of free radicals in skin: a review of the literature and new
      developments.

PMID- 11225192
TI  - Reactive oxygen species as mediators of UVB-induced mitogen-activated protein
      kinase activation in keratinocytes.

PMID- 11225193
TI  - Antioxidants in chemoprevention of skin cancer.

PMID- 11225194
TI  - Radical reactions of carotenoids and potential influence on UV carcinogenesis.

PMID- 11225195
TI  - Protective effects of topical antioxidants in humans.
AB  - Human studies have convincingly demonstrated pronounced photoprotective effects
      of 'natural' and synthetic antioxidants when applied topically before UVR
      exposure. Particularly with respect to UVB-induced skin damage such as erythema
      formation, the photoprotective effects of antioxidants are significant when
      applied in distinct mixtures in appropriate vehicles. Topical application of such
      combinations may result in a sustained antioxidant capacity of the skin, possibly
      due to antioxidant synergisms. And, since UVA-induced skin alterations are
      believed to be largely determined by oxidative processes [26], topical
      administration of antioxidants might be particularly promising [27, 28]. In fact,
      topical application of antioxidants or antioxidant mixtures resulted in a
      remarkable increase in the minimal dose to induce immediate pigment darkening
      after UVA exposure [18, 23] and diminished the severity of UVA-induced
      photodermatoses [22] in humans. In conclusion, regular application of skin care
      products containing antioxidants may be of the utmost benefit in efficiently
      preparing our skin against exogenous oxidative stressors occurring during daily
      life. Furthermore, sunscreening agents may also benefit from combination with
      antioxidants resulting in increased safety and efficacy of such photoprotective
      products [11, 29].

PMID- 11225196
TI  - The antioxidative potential of melatonin in the skin.

PMID- 11225197
TI  - Bioconversion of vitamin E acetate in human skin.

PMID- 11225198
TI  - Electron paramagnetic resonance detection of free radicals in UV-irradiated human
      and mouse skin.

PMID- 11225199
TI  - The antioxidant network of the stratum corneum.
AB  - Many studies have demonstrated beneficial health effects of topical antioxidant
      application; however, the underlying mechanisms are not well understood. To
      better understand the protective mechanism of oxogenous anti-oxidants, it is
      important to clarify the physiological distribution, activity and regulation of
      antioxidants. Also, the generation of ROS by the resident and transient microbial
      flora and their interaction with cutaneous antioxidants appears to be of
      relevance for the redox properties of skin. Our studies have demonstrated that
      alpha-tocopherol is, relative to the respective levels in the epidermis, the
      major antioxidant in the human SC, that alpha-tocopherol depletion is a very
      early and sensitive biomarker of environmentally induced oxidation and that a
      physiological mechanism exists to transport alpha-tocopherol to the skin surface
      via sebaceous gland secretion. Furthermore, there is conclusive evidence that the
      introduction of carbonyl groups into human SC keratins is inducible by oxidants
      and that the levels of protein oxidation increase towards outer SC layers. The
      demonstration of specific redox gradients within the human SC may contribute to a
      better understanding of the complex biochemical processes of keratinization and
      desquamation. Taken together, the presented data suggest that, under conditions
      of environmentally challenged skin or during prooxidative dermatological
      treatment, topical and/or systemic application of antioxidants could support
      physiological mechanisms to maintain or restore a healthy skin barrier. Growing
      experimental evidence should lead to the development of more powerful
      pharmaceutical and cosmetic strategies involving antioxidant formulations to
      prevent UV-induced carcinogenesis and photoaging as well as to modulate
      desquamatory skin disorders.

PMID- 11225200
TI  - Activity of alpha-lipoic acid in the protection against oxidative stress in skin.

PMID- 11225201
TI  - Ozone: an emerging oxidative stressor to skin.

PMID- 11225202
TI  - Effects of UV and visible radiations on cellular DNA.

PMID- 11225203
TI  - Sequence-specific DNA damage induced by UVA radiation in the presence of
      endogenous and exogenous photosensitizers.

PMID- 11225204
TI  - UV-induced oxidative stress and photoaging.

PMID- 11225205
TI  - UVA and singlet oxygen as inducers of cutaneous signaling events.

PMID- 11225206
TI  - The metrics of organizational excellence.

PMID- 11225207
TI  - Is your Website ADA compliant?

PMID- 11225208
TI  - Product line marketing: a strategy for growing net income.

PMID- 11225209
TI  - Vital signs for your cardiovascular services.
AB  - Current trends and "best practice" operating statistics can be vital to the
      success of today's cardiovascular programs. The findings from a recently
      published survey entitled, "Trends in Cardiovascular Programs: A National
      Benchmarking Study", provide the administrator with immediate and current
      knowledge of best ways to manage cardiovascular services to succeed in a
      competitive market. Study results provide some interesting and valuable
      information regarding non-invasive cardiology, cardiac catheterization, and
      peripheral vascular angiography program administration and provide insight into
      issues of cost, quality, and cardiovascular program concerns, interests and
      needs.

PMID- 11225210
TI  - Hepatitis C virus and hemodialysis.

PMID- 11225211
TI  - Hepatitis C virus infection during haemodialysis in India.
AB  - BACKGROUND: Hepatitis C viral (HCV) infection is a major cause of hepatitis
      during haemodialysis after the control of hepatitis B following vaccination and
      isolation measures. Magnitude of this problem in India has not been studied and
      there are only few reports of HCV infection during haemodialysis from this
      country. This study was conducted to find out the incidence of HCV infection in
      patients of end stage renal disease (ESRD) and haemodialysis (HD), along with its
      source and to find out the clinical course of HCV positive patients. METHODS: HCV
      infection was diagnosed by detecting anti-HCV antibodies using the IIIrd
      generation ELISA kits. RESULTS: Of the 208 consecutive patients of ESRD accepted
      for the study, HCV prevalence was 4.3% at the time of start of study. Of the all
      risk factors studied, past history of jaundice and number of blood transfusion
      (BT) were significantly higher in HCV positive patients as compared to HCV
      negative patients. Of the 208 patients, 20 (9.6%) died, 119 (57.2%) lost follow
      up and 69 (33.2%) got renal transplant (RT). Incidence of HCV in patients who
      died, lost follow-up and got RT was 10%, 3.4% and 36.2% while prevalence was 15%,
      4.2% and 42% respectively. In these groups, duration of HD was 8.4, 5.2 and 22.7
      weeks respectively while the mean blood transfusion (BT) was 1.2, 0.8 and 5.4 in
      number respectively. Mean age of patients in these groups was 37.85, 37.9 and
      32.53 years and percentage of males were 65%, 75% and 89.9% respectively. At no
      stage of follow-up, patients with HCV infection had any symptoms or high serum
      bilirubin. Major abnormality was fluctuating ALT in these patients. HCV in 512
      units of blood transfusions given to these patients and healthy volunteers was
      1.17% and 0.66% respectively. Marked increase of HCV infection while patients
      were on HD is likely to be due to nosocomial spread. Blood transfusion was not
      found to be important source of HCV infection. Longer the patients remain on HD;
      more will be chance of HCV infection. CONCLUSION: It is concluded that HCV is a
      major cause of concern in haemodialysis patients in India and the predominant
      source of spread of infection is nosocomial. In our set-up, blood transfusion is
      not an important source of infection. Majority of these patients remains
      asymptomatic at least for the short terms follow-up.

PMID- 11225212
TI  - Patients with malnutrition related diabetes mellitus are as insulin sensitive as
      insulin dependent diabetics.
AB  - OBJECTIVES: High insulin requirement is considered as indicative of insulin
      resistance in malnutrition related diabetes mellitus (MRDM). Hyperinsulinemic
      euglycemic clamp technique (HECS) is the gold standard to assess insulin
      sensitivity in vivo. Hence we carried out HECS in a group of MRDM and compared it
      to subjects with insulin dependent diabetes mellitus (IDDM) to assess whether
      patients with malnutrition related diabetes mellitus have lower insulin mediated
      glucose disposal than IDDM. METHODS: In a case control design insulin mediated
      glucose disposal assessed by HECS at insulin infusion rate of 40 mU/m2 during
      steady state of 60-120 minutes. Mean coefficient of variation of plasma glucose
      during 60-120 minute steady state was 3.58 +/- 0.33 mg%. Whole body glucose
      disposal rate ("M" value) was expressed in mg/kg/min, which was equal to the
      glucose infused under steady state plasma glucose concentration during last one
      hour of HECS. RESULTS: Insulin mediated glucose disposal was measured in MRDM and
      compared with ketosis prone diabetes of young (IDDM) by HECS. Both groups were
      matched for age (23.4 +/- 1.8 vs. 19.8 +/- 2.5 years) and BMI (16.7 +/- 0.6 vs.
      18.5 +/- 0.6 kg/m2). They were also comparable in duration of illness (4.4 +/-
      1.0 vs. 4.5 +/- 1.0 years) and WHR (0.87 +/- 0.02 vs. 0.83 +/- 0.02). Patients in
      both groups had comparable glycemic control (HbAl 12.1 +/- 0.54 vs. 10.5 +/-
      1.2), serum cholesterol (145 +/- 11 vs. 167 +/- 21 mg/dl) and serum triglyceride
      levels (147 +/- 13 vs. 110 +/- 9 mg/dl). Glucose disposal rate (M-value,
      mg/kg/min) during 60-120 minutes (7.06 +/- 0.80 vs. 7.50 +/- 0.87) and during 100
      120 minutes (7.76 +/- 0.96 vs. 7.75 +/- 1.25) was not different in the two
      groups. CONCLUSIONS: High insulin requirement considered as indicative of insulin
      resistance in atypical ketosis resistant young diabetics is not due to insulin
      resistance.

PMID- 11225213
TI  - Herpes simplex virus-1 encephalitis in eastern Uttar Pradesh.
AB  - OBJECTIVE: To study the proportion of HSV-1 encephalitis in acute viral
      encephalitis. METHODS: One hundred and five patients presenting with clinical
      diagnosis of acute viral encephalitis and with exclusion of other possible causes
      of acute inflammatory brain disease prevalent in the area by relevant laboratory
      investigations were included in the study. Ninety single CSF samples were tested
      for HSV-1 IgM antibodies by ELISA test supplied by Dia Medix Corporation, USA. CT
      Scan and EEG studies were carried out in 25 patients. RESULTS: Clinical and neuro
      investigational profile of patients suggested a low incidence of HSV-1
      encephalitis in the study group. IgM antibodies were present in CSF sample of one
      patient only. CONCLUSION: HSV-1 encephalitis constitutes a very low proportion
      (1.1%) of acute viral encephalitis cases seen in Eastern Uttar Pradesh (India).

PMID- 11225214
TI  - Prevalence of vascular complications and their risk factors in type 2 diabetes.
AB  - OBJECTIVE: a) To determine the prevalence of microvascular and macrovascular
      complications in Type 2 diabetes in India and b) to identify the major factors
      for the complications. METHODS: A study was done in 3010 subjects (M:F 1892:1118,
      Mean age 52 +/- 9.7 years) attending a diabetic clinic. The study sample
      resembled the population sample in anthropometry, age and socioeconomic factors.
      All patients had undergone the tests for retinopathy, nephropathy, neuropathy,
      peripheral vascular disease (PVD) and cardiovascular disease by ECG. RESULTS:
      Retinopathy was diagnosed in 23.7% (background retinopathy in 20.0% and
      proliferative in 3.7%), proteinuria was present in 19.7% and persistant
      proteinuria of > or = 500 mg/dl was seen in 5.5% of them, CHD was present in
      11.4% and PVD was present in 4.0%. Of the total 119 cases with PVD, 18 had
      gangrene and 21 had undergone amputations. Peripheral neuropathy was present in
      27.5%. Cerebrovascular accidents were reported in 26 cases (0.9%). Hypertension
      was present in 38% of the cases. Multiple logistic regression analyses showed
      that age had a significant association with retinopathy, neuropathy, CHD and PVD.
      Duration of diabetes had significant association with the complications other
      than CHD. Higher HbA1 increased the risk of retinopathy, neuropathy and
      nephropathy. Hypertension was associated with the complications except PVD and
      neuropathy. The strongest association was between hypertension and nephropathy.
      CONCLUSION: The study highlights the high prevalence of vascular complications in
      Type 2 diabetes in India. Retinopathy and neuropathy were the commonest
      complications of diabetes.

PMID- 11225215
TI  - Lipoprotein(a) and coronary heart disease in Indian population.
AB  - OBJECTIVE: Present study was undertaken to evaluate the role of lipoprotein(a) in
      coronary heart disease (CHD) patients and its relationship with other established
      risk factors. METHODS: Blood samples of 67 control patients (non-cardiovascular
      problems) and 222 CHD patients (> or = 4 weeks post myocardial infarction) were
      analyzed. Lipoprotein(a) was measured in serum samples by enzyme-linked
      immunosorbent assay utilizing rabbit polyclonal antibodies against purified human
      Lp(a). Step-wise linear discriminant analysis was used to find the important
      parameters to discriminate CHD and non-CHD subjects. RESULTS: The LDL to HDL
      cholesterol ratio (p < 0.01) and serum level of lipoprotein(a) (p < 0.01) were
      significantly higher in CHD patients. Levels of lipoprotein(a) were found to be
      higher in females compared to males (p < 0.01). Positive family history of CHD
      did not show significant difference in Lp(a) levels. Lp(a) level in CHD patients
      with positive family history of NIDDM and hypertension was higher than in with
      negative family history. CONCLUSION: Clinical significance of serum level of
      Lp(a) and albumin in determining the risk of CHD has been observed. Lp(a) alone
      could correctly discriminate a CHD individual from a control subjects by 95%.
      Estimating of Lp(a) together with albumin provided 99% correct discrimination
      between control and CHD patients. These results also suggest that Lp(a) together
      with malnutrition could be responsible for the increased incidence of CHD in
      Indians. It is also indicated that in females atherothrombogenic potential of
      lipoprotein(a) remains suppressed before menopause but after this stage women
      lose this advantage.

PMID- 11225216
TI  - Relationship between osteoarthritis of knee and menopause.
AB  - AIM: To study the difference in the onset of osteoarthritis (OA) between males
      and females with respect to age and to note the relationship between OA of the
      knees and menopause and hysterectomy in females. MATERIAL AND METHODS: One
      hundred consecutive patients (50 males and 50 females) were studied for the onset
      of OA and compared for the statistical difference. In females the relationship
      between onset of OA and menopause and hysterectomy, if done, was noted. RESULTS:
      Fifty eight percent of females had onset of symptoms of OA of knees before 50
      years of age as compared to only 20% in males (p < 0.05). Sixty four percent of
      females with OA of knees had the onset of symptoms either perimenopausally or
      within five years of natural menopause or hysterectomy. CONCLUSION: There is a
      definite early peaking of the incidence of OA of knees in women in the fifth
      decade of life as compared to males. There is an association between OA of knees
      and menopause and we suggest correlating it with the levels of sex hormones.

PMID- 11225217
TI  - Difference in body fat percentage does not explain the gender dimorphism in
      leptin in Asian Indians.
AB  - OBJECTIVE: Leptin is a hormone probably having regulatory function on energy
      intake and metabolic activities in humans. The study was done: (a) To determine
      the relation of leptin with the body fat% in Indians, (b) To see whether the
      differences in body fat accounted for the gender differences in the concentration
      of leptin and (c) to look for the effect of diabetes on the levels of leptin.
      METHODS: Glucose tolerance was determined by oral glucose tolerance test (GTT) in
      87 subjects with no known history of diabetes. Leptin was estimated by radio
      immuno assay. Age, height, weight, waist and hip circumferences were noted. Body
      mass index (BMI, weight kg/height m2) and waist:hip ratio (WHR) were calculated.
      The body fat % was estimated by bioelectrical impedance analysis. RESULTS: Leptin
      correlated with log fat % and BMI, body weight and waist circumference in
      different categories of glucose tolerance (Pearson's correlation test). Leptin
      values were higher in women than in men even after correcting for the body fat %
      indicating that the gender dimorphism was not explained by the higher fat % in
      women. The geometric mean of leptin concentration in men was 3.6 ng/ml and in
      women 10.9 ng/ml (P < 0.0001). Leptin level were not influenced by the status of
      glucose tolerance. Gender showed a significant effect on leptin concentration (F
      = 11.0, df = 1.39, P = 0.002) after adjusting for the effect of covariates i.e.
      percentage of fat (log), BMI, age, WHR and 2 h plasma glucose by ANCOVA. None of
      the covariates except BMI (P < 0.0001) showed significant correlation with
      leptin. The total variance explained was 68.4%. CONCLUSION: We conclude that (1)
      Plasma leptin is strongly correlated to the body fat content (2) the gender
      dimorphism of leptin is not explained by the differences in fat percentage and
      (3) hyperglycemia does not influence plasma leptin levels.

PMID- 11225218
TI  - Lesser known clinical features of dengue fever.

PMID- 11225219
TI  - A preliminary trial of serratiopeptidase in patients with carpal tunnel syndrome.
AB  - OBJECTIVES: This study was planned to assess the response of serratiopeptidase in
      patients with carpal tunnel syndrome (CTS). METHODS: Twenty patients with CTS
      were evaluated clinically. After baseline electrophysiological studies, these
      patients were given serratiopeptidase 10 mg twice daily with initial short course
      of nimesulide. Clinical and electrophysiological reassessment was done after 6
      weeks. RESULTS: Mean age was 43.9 years with male to female ratio of 1:2.33.
      Sixty five percent cases showed significant clinical improvement which was
      supported by significant improvement in electrophysiological parameters.
      Recurrence was reported in four cases. No significant side effect was observed.
      CONCLUSIONS: Serratiopeptidase therapy may proved to be a useful alternative mode
      of conservative treatment. Larger study may be further helpful to establish the
      role of serratiopeptidase in CTS.

PMID- 11225220
TI  - Patients' adherence to diabetes treatment.
AB  - OBJECTIVES: a) To evaluate the patients' adherence to the treatment prescriptions
      and b) to analyse the reasons for non adherence. METHODS: A random sample of 386-
      type 2 diabetic subjects (M:F 223:163) were studied. Each subject was personally
      interviewed using a computerised proforma. The mean age of the study group was 52
      +/- 10 years and 53% were treated with oral hypolycenic agent (OHA) and the rest
      with a combination of insulin and OHA. The mean duration of diabetes was 11.0 +/-
      6.9 yrs. The overall adherence to the treatment regimen, diet and drug
      prescriptions and also regularity of home glucose monitoring by blood or urine
      tests were assessed. RESULTS: It was noted that only 25% of the study group were
      adhering to the treatment regularly. Dietary prescriptions were followed
      regularly only by thirty seven percent. Home glucose monitoring was being done
      only by twenty three percent. Non adherence was not related either to the age or
      duration of diabetes. Non adherence was more in the lower socio-economic group
      and was inversely related to the educational status. It was noted that
      approximately 20% of the subjects had an indifferent attitude to the advice
      given. CONCLUSIONS: The results showed that the rate of non adherence of
      treatment prescriptions was high. It stresses the need for constant motivation
      and one to one level education at frequent intervals to ensure better compliance
      to the treatment.

PMID- 11225221
TI  - Diabetic gastroparesis.
AB  - Our understanding of gastric motility disorder--diabetic gastroparesis has
      advanced in the last ten to fifteen years, but the published data regarding
      pathogenesis are confusing and show conflicting results. The pathogenesis is
      sometimes linked with hyperglycemia, autonomic neuropathy, gastrointestinal
      hormone or myogenic mechanism. Antral hypomotility is often associated with
      hyperglycemia which is often accompanied by reduction in duodenal waves. Varying
      level of motilin, a gastrokinetic hormone has been reported. However none of the
      mechanism could explain the exact pathogenesis. The relationship of this
      mortality disorder with clinical symptoms is not always established, however
      nausea and vomiting lasting for days or weeks are the prominent symptoms. Other
      symptoms are post-prandial fullness, early satiety, bloating, belching, and vague
      abdominal discomfort. In a few cases, it may be the cause of poor nutrition,
      uncontrolled diabetes and recurrent ketoacidosis. Last one or two decades have
      seen some advancement in the investigational procedures like scintigraphy, radio
      opaque markers, breath test, electrogastrography and MRI. Which can lead to a
      proper diagnosis. Such objective assessment is all the more important as nearly
      half of the patients do not have any symptom. Symptomatic improvement of
      gastroparetic patients should be the aim and in asymptomatic patients, treatment
      is often not recommended. Some dietary advice and prokinetic agents like
      metoclopramide, cisapride etc. are often prescribed but much needs to be further
      known as management is not always uniformly rewarding.

PMID- 11225222
TI  - Genetic variation and nutrition in relation to coronary artery disease.
AB  - There is evidence that coronary artery disease (CAD), hypertension, diabetes
      mellitus (DM) and hyperlipidemia develop due to interaction of genetic and
      environmental factors during transition from poverty to affluence. Rapid
      transition in diet and lifestyle factors may influence heritability of the
      variant phenotypes that are dependent on the nutrient environment for their
      expression. We are beginning to recognize the interaction of specific nutrients
      with the genetic code possessed by all nucleated cells. In the next millennium,
      the physician may be able to make nutrient intake recommendations not on physical
      characteristics but on the basis of the individual's phenotypic expression for
      health while suppressing his phenotypic expression for disease. We have
      demonstrated an increased susceptibility to CAD, diabetes, central obesity,
      hyperinsulinemia and lipoprotein(a) excess in Indians in younger age groups
      indicating a genetic predisposition to these problems due to interaction of gene
      and environment. Lipoprotein(a) is a genetic risk factor for CAD, diabetes and
      stroke and it is higher in South Indians than North Indians. Antioxidant
      vitamins, coenzyme Q10 and n-3 fatty acids may have a beneficial influence
      whereas linoleic acid, saturated fat and sugars may have adverse effects on
      phenotypic expression. There is significant evidence that genes are involved in
      determining enzymes, receptors, cofactors, structural components involved in
      regulation of blood pressure, the metabolism of lipids, lipoproteins and
      inflammatory and coagulation factors that are involved in determining an
      individual's risk. Majority of these genes are polymorphic. While some genes
      respond to nutritional modulation, others may not indicate any response.

PMID- 11225223
TI  - Genes, dreams and realities.

PMID- 11225224
TI  - Acute nonspecific carditis in adolescents presenting with Stokes-Adams attacks.
AB  - Three patients, aged between 12 and 17 years presented with Stokes-Adams attacks
      as a result of atrioventricular block, atrioventricular silence and ventricular
      arrhythmias, complicating acute myocarditis. All the patients required temporary
      pacing for a few days. One patient required hemodialysis for anuria. All the
      patients made complete recovery.

PMID- 11225225
TI  - Cyclospora cayetanensis--an emerging coccidian parasite.
AB  - Over the last decade increasing number of enteritis cases have been attributed to
      infection with a new coccidian sp that was named Cyclospora cayetanensis in 1993.
      Diarrhoea caused by this agent is clinically indistinguishable from
      cryptosporidiasis, isosporiasis and microsporidiasis but cyclospora infection are
      often very prolonged (upto 15 weeks) and may cause severe weight loss. Diagnosis
      is important because unlike diarrhoea caused by cryptosporidium and
      microsporidium, treatment with co-trimoxazole is effective. We report here a case
      of cyclosporiasis, to increase awareness of possibility of cyclospora infection
      in patients with prolonged diarrhoea. It should be considered in assessment of
      patients with unexplained prolonged diarrhoeal illness.

PMID- 11225226
TI  - Alien hand syndrome.

PMID- 11225227
TI  - Favourable outcome in a patient with central nervous system lupus.
AB  - We report a case of paediatric lupus who during her admission developed near
      fatal central nervous system complication of status eilepticus with respiratory
      paralysis and was managed with intravenous immunoglobulins, extended course of
      methyl prednisolone with a favourable outcome.

PMID- 11225228
TI  - Anomalous left coronary artery from pulmonary artery.

PMID- 11225229
TI  - Amelogenesis imperfecta and distal renal tubular acidosis presenting as
      hypokalemic periodic paralysis.

PMID- 11225230
TI  - Hepatitis E associated with acute pancreatitis with pseudocyst.

PMID- 11225231
TI  - Lichen scrofulosorum--a rare manifestation of a common disease.

PMID- 11225232
TI  - Parameningeal embryonal rhabdomyosarcoma in an adult.

PMID- 11225233
TI  - Isolated left main coronary ostial stenosis in a young female.

PMID- 11225234
TI  - Bilateral phaeochromocytoma.

PMID- 11225236
TI  - Socio-psychological aspects of artificial sex change.

PMID- 11225235
TI  - The circadian pattern of ischaemic heart disease events in Indian population.

PMID- 11225237
TI  - Neuroelectrophysiological diagnosis of a case of neurological deficit with
      vomiting and diarrhoea.

PMID- 11225238
TI  - Labelling of drug ampoules in India.

PMID- 11225239
TI  - Vivax malaria: also a challenge to biomedical sciences and services.

PMID- 11225240
TI  - Time to don the business suit.

PMID- 11225241
TI  - MRI in cobalamine deficiency.

PMID- 11225242
TI  - Side effect of ACE inhibitor.

PMID- 11225243
TI  - [Re-recognition of malignant histiocytosis].

PMID- 11225244
TI  - [Multiple myeloma].

PMID- 11225245
TI  - [Study of IL-6 signal transduction pathway in a human multiple myeloma cell line-
      Sko-007].
AB  - OBJECTIVE: To investigate the IL-6 signal transduction pathway in a human
      multiple myeloma (MM) cell line--Sko-007. METHODS: The electrophoretic mobility
      shift assay (EMSA) and immunoprecipitation were used to detect the activation of
      IL-6-related transcription factors(TFs)--STAT3, NF-IL-6, NF-kB and protein kinase
      ERK, Jak1 in Sko-007 cells stimulated by IL-6. RESULTS: Both the transcription
      factors-STAT3, NF-IL-6 and protein kinases-Jak1, ERK were activated by IL-6 in
      Sko-007 cells. CONCLUSION: The biological function of IL-6 on Sko-007 cells is
      mediated by the activation of Jak/STAT and Ras/NF-IL-6 signal transduction
      pathways.

PMID- 11225246
TI  - [The expression, secretion and regulation of membrane-soluble syndecan-1 in human
      multiple myeloma cells].
AB  - OBJECTIVE: To analyze the expression, secretion and regulation of membrane
      soluble syndecan-1 in human multiple myeloma cells, and to explore the
      relationship between syndecan-1 and the development of human multiple myeloma.
      METHODS: Syndecan-1 expression on the surface of malignant plasma cells was
      analyzed by immuno-staining, the levels of soluble syndecan-1 in the supernatant
      of cultured tumor cells by ELISA. RESULTS: 1. Human multiple myeloma cells
      expressed high levels of syndecan-1. The density of syndecan-1 varied from
      170,000 to 800,000 molecules per cell. The expression of syndecan-1 lost rapidly
      as the cells underwent apoptosis. 2. Most myeloma cells produced soluble syndecan
      1, the rate of production did not correlate with the density of membrane syndecan
      1. Moreover, the production of soluble syndecan-1 did not require serum. 3. The
      protein synthesis inhibitor cycloheximide inhibited the production of syndecan-1.
      The serine protease inhibitor antipain did not affect the secretion of syndecan
      1. CONCLUSION: As a receptor of many growth factors, cytokines and heparin-like
      growth factors, syndecan-1 might play an important role in tumor cell growth and
      homing in multiple myeloma development.

PMID- 11225247
TI  - [The efficacy of L-asparaginase in the treatment of refractory midline peripheral
      T-cell lymphoma].
AB  - OBJECTIVE: To improve the treatment outcome of refractory midline peripheral T
      cell lymphoma (MPTCL). METHOD: Eleven patients with refractory MPTCL received
      salvage chemotherapy consisting of L-asparaginase(L-ASP), vincristine and
      dexamethosone (L-ASP group), and 10 patients received combined chemotherapy
      without L-ASP(control group). The response rates and 2 year survival rates were
      observed. RESULTS: Response rates were 63.6% for L-ASP group and 10.0% for
      control group (P < 0.05), and 2 year survival rates were 45.5% and 0 (P < 0.05),
      respectively. The major side effects of L-ASP were leukocytopenia, elevation of
      serum bilirubin and hyperglycemia. CONCLUSION: The L-ASP-based salvage
      chemotherapy improved the response rate and 2 year survival rate of the patients
      with refractory MPTCL.

PMID- 11225248
TI  - [An analysis of the clinical and laboratory data of 53 cases of non-Hodgkin's
      lymphoma].
AB  - OBJECTIVE: To analyse the influence of factors on the prognoses of non-Hodgkin's
      lymphoma (NHL) and the clinical usage of IgH and T cell receptor(TCR) gene
      rearrangement for NHL typing. METHODS: Immunological phenotyping was carried out
      by SABC, and IgH(FR2A, FR3A) and TCR(beta, gamma) detection by PCR. RESULTS: The
      age curve of NHL was increased parallel with the patient's age increasing, hazard
      ratio was increased 1.039n annually. The incidence of B cell NHL(B-NHL) was
      66.7%, T cell NHL(T-NHL) was 31.1%, low grade NHL was 56%, middle and high grade
      NHL were 44%. The positivity of IgH and TCR gene rearrangement in NHL patients
      were 75% by PCR detection, T and B classification was same as phenotyping. The 3
      and 5 years survival ratio: HD were 83.3% and 62.5%, stage I-II of NHL were 88.9%
      and 66.7%, stage III-IV of NHL were 39.9% and 33.3%, Low grade NHL were 65.1% and
      48.8%, middle and high grade NHL were 47.6% and 39.6%. The survival time of
      APBSCT group was longer than that of the conventional therapy group. CONCLUSION:
      Age, T,B classification, grading and staging are the important factors which
      affect on NHL prognoses. APBCST can improve NHL prognoses, especially for those
      of stage III-IV patients. Molecular biological methods can help T/B
      classification when it couldn't be confirmed by phenotyping.

PMID- 11225249
TI  - [Clinical analysis of 10 cases of true histiocytic lymphoma].
AB  - OBJECTIVE: To explore the clinical and pathological characteristics of true
      histiocytic lymphoma. METHODS: The clinical and pathological data of 10 true
      histiocytic lymphoma patients admitted between 1986 and 1996 to our hospital was
      retrospectively reviewed. RESULTS: True histiocytic lymphoma accounted for 0.6%
      of non-Hodgkin's lymphoma(NHL) admitted in this period to our hospital. Enzymes
      associated with true histiocytic lymphoma were detected in all the 10 cases. The
      tumor cells were excluded from T/B lymphoid origin in 6 cases by
      immunohistochemistry. Eight cases received chemotherapy + irradiation +/-
      excision of primary lesion, 1 simply received irradiation and 1 received bone
      marrow transplantation. The response rate was 100%, with a 1, 3 and 5 year
      survival rate of 100%, 90% and 70%, respectively. The expected 10 year disease
      free survival rate is 40%. CONCLUSION: True histiocytic lymphoma is a rare subset
      of NHL. Those originated from lymph node are sensitive to chemotherapy and
      irradiation with a favorable prognosis.

PMID- 11225250
TI  - [The correlation of cytokines TNF alpha, IFN-gamma, Epo with anemia in rheumatoid
      arthritis].
AB  - OBJECTIVE: To elucidate the characteristics of anemia of chronic disease(ACD) in
      rheumatoid arthritis(RA), and the role of TNF alpha, IFN-gamma and Epo in the
      pathogenesis of ACD. METHOD: Serum TNF alpha and IFN-gamma levels in RA patients
      and serum Epo levels in RA with ACD were measured by ELISA. Serum iron status
      profile in RA patients were also detected. The effects of TNF alpha and IFN-gamma
      on cobalt-induced erythropoietin production in human hepatic cancer cells(HepG2)
      were examined. The effect of TNF alpha and IFN-gamma erythroid colony formation
      (CFU-E and BFU-E) of normal bone marrow cells, and the effect of serum from RA
      patients and Epo on CFU-E yields of RA bone marrow cells. RESULT: Serum TNF alpha
      or IFN-gamma in RA and RA with ACD patients were higher than those in normal
      controls, and were inversely correlated with hemoglobin, and serum iron levels.
      Serum Epo levels in ACD patients were lower than those in iron-deficiency anemia
      patients with comparable hemoglobin level. TNF alpha and IFN-gamma could
      specifically inhibit cobalt-induced Epo production in HepG2 cells, and suppressed
      normal bone marrow BFU-E and CFU-E growth in a dose-dependent manner. Bone marrow
      CFU-E yields of RA patients were also suppressed by their own serum. The
      inhibitory effects of TNF alpha, IFN-gamma or serum from RA patients on erythroid
      colony formation could be corrected by the addition of rhEpo. CONCLUSION: It
      suggested that there were hematopoietic inhibiting factors in the serum of RA
      patients. TNF alpha or IFN-gamma was involved in the pathogenesis of anemia in RA
      patients. Administration of rhEpo might be beneficial for anemia of RA patients.

PMID- 11225251
TI  - [The promoting effects of mGM-CSF gene modified tumor vaccine immunization on
      peritoneal antigen presenting cells in mice].
AB  - OBJECTIVE: To investigate the effects of immunization with granulocyte-macrophage
      colony-stimulating factor (GM-CSF) gene-modified tumor vaccine on the number and
      function of antigen presenting cells (APCs). METHODS: FBL-3 murine
      erythroleukemia cells were transfected with mGM-CSF recombinant adenovirus and
      then irradiated to prepare vaccine. The specific cytotoxic T lymphocyte(CTL)
      activity in vivo and survival of the mice i.p. immunized with this vaccine were
      observed. The percentage of 33D1+ dendritic cells(DCs) in peritoneal adherent
      cells were analyzed with flow cytometry. The number of peritoneal cell and
      function of peritoneal adherent cells of immunized mice were also investigated.
      RESULTS: High level of specific CTL activity were induced in the mice i.p.
      immunized with this vaccine and all of the mice were resistant to the subsequent
      challenge with the parental FBL-3 cells. The number of peritoneal APCs-increased.
      FACS analysis showed that the percentage of 33D1+ DCs in peritoneal adherent
      cells also increased. The allo-mixed lymphocyte reaction(MLR) stimulating
      activity of these APCs was enhanced. CONCLUSION: mGM-CSF gene-modified tumor
      vaccine has potent anti-tumor effect, and this may be related to the increased
      number and function of peritoneal APCs induced by mGM-CSF through paracrine
      mechanism at the vaccination site.

PMID- 11225252
TI  - [Expression of recombinant human soluble Flt3 ligand and its in vitro effects on
      malignant hematopoietic cells].
AB  - OBJECTIVE: To express human soluble Flt3 ligand in a yeast expression system.
      Pichia pastoris, and investigate the effects of recombinant human soluble Flt3
      ligand (rhFL) on the proliferation of malignant hematopoietic cells(MHC) and the
      effect of dexamethasone (DXM) on the expression of Flt3 receptor (Flt3R) and the
      rhFL induced proliferation of those cells. METHODS: An artificial gene for rhFL
      was synthesized by using favored genetic codons of the yeast Pichia pastoris.
      Flt3R was determined by flow cytometry. Proliferation of MHCs was measured by
      microculture tetrazolium (MTT) assay. RESULTS: 1. An expression vector, pPICZ
      alpha A-FL, was constructed and electroporated into Pichia pastoris. A yield of
      over 30 mg/L of yeast culture supernatant was obtained. The rhFL could stimulate
      the proliferation of Raji and HL-60 cells at concentrations of 10-100 ng/ml, but
      did not for most of other MHCs. 2. Flt3R was expressed in 5 of 18 MHC lines and
      the expression in leukemic blast cells was widespread and extremely
      heterogeneous. 3. The presence of the receptor on the surface of MHC did not
      necessarily imply a significant ligand-induced response, at least in terms of
      proliferation. By contrast, some Flt3R-negative MHC responded to rhFL. 4. DXM
      down-regulated the expression of Flt3R and inhibited the proliferation induced by
      rhFL in some MHC lines and fresh leukemia cell samples. CONCLUSION: A yield of 30
      mg/L of rhFL was obtained. rhFL stimulated the proliferation of Raji, HL-60 cells
      and some fresh leukemia cells, which could be inhibited by DXM through down
      regulation of Flt3R. A combination of FL and DXM might possibly serve to control
      hematopoietic defects in malignant hematopoietic diseases.

PMID- 11225253
TI  - [Bupropion: an effective new aid for smoking cessation].

PMID- 11225254
TI  - [Severe lactic acidosis due to metformin ingestion in a patient with contra
      indication for metformin].

PMID- 11225255
TI  - [Diagnostic image (8). Intestinal amoebiasis].

PMID- 11225256
TI  - [Proximal muscle weakness, depressed tendon reflexes and autonomic dysfunction:
      the Lambert-Eaton myasthenic syndrome].
AB  - Three patients with Lambert-Eaton myasthenic syndrome (LEMS), two men aged 61 and
      64 and a woman aged 55 years, all developed proximal weakness, depressed tendon
      reflexes and autonomic dysfunction. Although this clinical triad is highly
      suggestive for LEMS, the disorder had not been recognized initially. The woman
      had a small-cell bronchial carcinoma, treated successfully by chemotherapy,
      whereafter the LEMS symptoms gradually disappeared. The first man was treated
      with 3,4-diaminopyridine and azathioprine, whereupon his symptoms diminished. The
      other man had only slight complaints and refused drug treatment. The three cases
      illustrate that presentation and course of LEMS can vary between patients.
      Furthermore, clinical and electrophysiological features can suggest myasthenia
      gravis, myopathy or axonal polyneuropathy. Therapeutic options and the risk of
      underlying malignancy make early diagnosis important. In conclusion, in every
      patient presenting with unexplained proximal weakness, LEMS should be considered,
      especially if depressed tendon reflexes and autonomic dysfunction are found as
      well.

PMID- 11225257
TI  - [Hormonal supplements for postmenopausal women: no evidence of protection against
      cardiovascular disease].
AB  - Atherothrombotic cardiovascular disease is a leading cause of death in women,
      especially in the postmenopause. It is controversial whether postmenopausal
      hormone replacement therapy is protective with regard to cardiovascular disease.
      On the one hand, observational studies consistently show that the risk of
      cardiovascular disease is 35 to 50% lower among users of hormonal replacement
      than among non-users. In addition, hormonal replacement is associated with an
      improvement of the lipid profile and several other potentially beneficial
      effects. On the other hand, two recent placebo-controlled randomised trials did
      not find evidence in favour of cardiovascular protection by hormonal replacement.
      This discrepancy may be explained by insufficient adjustment for lifestyle
      factors in observational studies and insufficient consideration of methodological
      flaws in experimental studies, both of which lead to an overestimation of the
      protective effect of hormonal replacement. Hormonal replacement may affect the
      pathophysiology of atherothrombosis in several ways, both positive and negative.
      Progress in this field requires the isolation of the positive effects.

PMID- 11225258
TI  - [Hormonal supplement therapy in women: effects on the cardiovascular system].
AB  - Coronary heart disease develops on average 10-15 years later in women than in men
      and is uncommon before menopause. 17 beta-estradiol has atheroprotective
      properties through rapid vasodilatory effects on the endothelium by stimulating
      nitric monoxide production and longer-term actions by modulating changes in gene
      expression. Cardioprotective effects of hormone replacement therapy in
      postmenopausal women have been suggested by observational data but not proved in
      randomized trials. Recent data indicate that oestrogens have regenerative effects
      on the vascular wall after acute injury, like a percutaneous transluminal
      coronary angioplasty. As endothelial reactivity declines with age, more studies
      are needed to investigate the benefits of hormone replacement therapy in the
      younger category of postmenopausal women.

PMID- 11225259
TI  - [Growth hormone receptor antagonists: potential indications].
AB  - Pegvisomant is a mutated human growth hormone molecule, which binds to the growth
      hormone receptor. This binding, however, does not lead to signal transduction.
      Therefore, in high concentrations pegvisomant acts as a growth hormone receptor
      antagonist. In a short term study (3 months) pegvisomant was shown to be an
      effective treatment for acromegaly. On theoretical grounds decreasing the
      biological effects of growth hormone in patients with diabetes mellitus could
      have a favourable impact on the severity of the secondary complications
      associated with this disease. Animal models for diabetic retino- and nephropathy
      are in accordance with this concept. Human data are lacking but clinical studies
      investigating the effect of pegvisomant in diabetes mellitus are in preparation.
      Growth hormone, either directly or via its downstream effector insulin-like
      growth factor-I (IGF-I) has been implicated as an important factor in the growth
      of malignant tumours. Animal studies in which human colon and breast cancer
      models were used showed that pegvisomant can powerfully decrease tumour growth.
      Studies in cancer patients have not yet started.

PMID- 11225260
TI  - [Roaming through methodology: XXIX. P].
AB  - The abundant use of p-values and statistical significance in medical literature
      often leads to invalid conclusions about the reported study results. A
      statistically significant result may be clinically irrelevant, while a clinically
      relevant effect may be ignored due to lack of statistical significance. These
      false conclusions can be attributed to the fact that p-values are often
      considered as a measure of relevance, validity and precision of a study outcome.
      A p-value, however, only conveys information about precision. In addition, a more
      informative means to describe the precision of a study exists, viz. confidence
      intervals. It is therefore important that both the editors of medical journals
      and the authors of scientific papers continue to use confidence intervals instead
      of p-values.

PMID- 11225261
TI  - [From gene to disease; tumor necrosis factor receptor and a syndrome of familial
      periodic fever].
AB  - Familial Hibernian fever (FHF) is a rare hereditary syndrome that causes periodic
      attacks of fever and inflammation. It is an autosomal dominantly inherited
      disorder. The gene involved in FHF encodes for a receptor for tumour necrosis
      factor (TNFR1). These mutations are thought to result in impaired shedding of the
      receptor from the cell membrane, leading to deficient curtailing of the
      inflammatory reaction. The acronym TRAPS (TNF-receptor associated periodic
      syndrome) has been proposed as a more accurate name.

PMID- 11225262
TI  - [Diagnostic image (20). Prolapsed submucous fibromyoma].
AB  - In a 48-year-old woman suffering from acute strong pain in the lower abdomen
      spontaneous partial delivery of a submucous fibromyoma was diagnosed.

PMID- 11225263
TI  - [Surgical treatment of hypoplastic left heart syndrome: limited success].
AB  - OBJECTIVE: To inventory the treatment of hypoplastic left heart syndrome (HLHS)
      in the Netherlands and its results. DESIGN: Retrospective. METHOD: Data were
      collected from all patients (n = 117) diagnosed with HLHS in the Wilhelmina
      Children's Hospital-University Medical Center Utrecht and the University Hospital
      Rotterdam-Sophia Children's Hospital and born in the period 1 March 1988-31 May
      2000. Type and time of intervention, and mortality were recorded and cumulative
      survival was analysed by Kaplan-Meier analysis. Cumulative survival was compared
      between early and late series and between the two hospitals. RESULTS: The study
      group comprised 68 boys and 49 girls, all neonates. At the time of the
      investigation, the mean duration of follow-up was 185 days (range: 0-3855). Fifty
      eight children had received no treatment; all of these had died. Fifty-nine
      children were scheduled for the Norwood procedure; six of them died before
      operation. The 53 patients who underwent the first stage of the Norwood procedure
      had 1-month, 1-year, 2-year, and 5-year survival chances of 55%, 30%, 27%, and
      24% respectively. Survival chances between the two time periods and the two
      hospitals showed no significant differences. CONCLUSION: The Norwood procedure
      was performed in almost half of the children with HLHS. It is only moderately
      successful; however, it seems the only realistic choice in the management.

PMID- 11225265
TI  - [Endophthalmitis after cataract surgery].
AB  - Endophthalmitis is one of the most serious complications after surgery of
      cataract. The reported incidence is 0.07 to 0.58%. The authors evaluate a group
      of 34 cases of endophthalmitis from a total of 13,247 eyes operated on account of
      cataract in 1990 to 1999 at the ophthalmological department of the Central
      Military Hospital. They describe the method used and the results. The conclusions
      are summarized as follows: 1. Early pars plana vitrectomy in developing
      endophthalmitis improves the chances of maintaining satisfactory visual
      functions. 2. After the change to ambulatory surgery the authors did not record a
      higher percentage of postoperative endophthalmitis. 3. As a rule surgical
      solution of endophthalmitis does not call for IOL.

PMID- 11225266
TI  - [Kraupa's retinal vein (case reports)].
AB  - The authors describe four cases of rare and yet little known anomaly of the
      central retinal vein trunc exit on optical disc. All the anomalies occurred in
      myopic eyes with higher refractive errors. They did not cause of any retinal and
      choroidal vascular disturbances.

PMID- 11225267
TI  - [Normal values of intraocular pressure in children].
AB  - To assess normal intraocular pressure values of the child population the authors
      examined a group of 215 children aged 4 to 15 years with a normal
      ophthalmological finding, a total of 406 eyes. All tonometric examinations were
      made without general anaesthesia or other pharmacological measures influencing
      the air-puff contact-free tonometer NT 1100 NIDEK, always the mean of three
      reliable results. Although there were certain variations of the intraocular
      pressure, they were not correlated to the child's age after the age of 4 years.
      The mean intraocular pressure in the whole group of 406 eyes was 16.08 +/- 3.08
      mm Hg. Knowledge of normal values of the IOP in children is important for
      diagnosis as well as for monitoring of already verified glaucoma.

PMID- 11225264
TI  - [Hypercalcemia due to chronic vitamin A use by an elderly patient with renal
      insufficiency].
AB  - An 86-year-old woman presented with anorexia, thirst and nycturia. Laboratory
      results revealed a hypercalcaemia with renal failure. The patient used 1-6
      vitamin A-D tablets daily (1 tablet contains 600 IU retinol palmitate and 200 IU
      cholecalciferol). The diagnosis was: hypercalcaemia due to chronic vitamin A
      ingestion. This diagnosis was supported by the finding of the elevated vitamin A
      concentration in the patient's serum and the exclusion of other causes of
      hypercalcaemia. In chronic vitamin A ingestion risk factors for vitamin A
      toxicity are age, body weight and renal insufficiency. The hypercalcaemia caused
      by chronic vitamin A ingestion is explained through the up-regulation of
      osteoclasts by retinol metabolites.

PMID- 11225268
TI  - [Effect of Trusopt on normal intraocular pressure values in children].
AB  - The authors investigated a group of 406 healthy eyes of children aged 4 to 15
      years to test the effect of the local carboanhydrase inhibitor TRUSOPT on natural
      previously assessed intraocular pressure. The measurements made by means of an
      air-puff contact-free tonometer NT 1100 NIDEK revealed a highly significant
      decline of intraocular pressure--from 16.08 mm Hg to 14.07 mm Hg on average in
      the whole group. The tolerance of the drug after a single administration caused
      no problems, no undesirable effect was recorded. This is the first and only
      report on the effect of TRUSOPT on normal intraocular pressure of the child eye
      reported in the literature in a statistically significant group. The authors are
      surprised by the fact that the possibility of favourable pharmacological
      treatment of child glaucoma with clinically widely used Trusopt is not used so
      far.

PMID- 11225269
TI  - [Treatment of postoperative astigmatism after perforating keratoplasty using the
      LASIK method].
AB  - The problem of postoperative astigmatism after perforating keratoplasty is
      complicated. Several possible methods of correction exist. The time and approach
      to correction of astigmatism after perforating keratoplasty is important. The
      authors present an account on a group of 10 eyes treated by the LASIK method on
      an apparatus Keracor 117. In four instances hyperopia with astigmatism was
      involved and in six eyes myopia with astigmatism, the mean age of the patients
      being 46.25 years. The mean values of the preoperative spherical hyperopic
      componenent was +1.37 D and of the myopic spherical component -2.12 D. The
      preoperative hyperopic astigmatism was +4.5 D and the myopic astigmatism -5.84 D.
      The follow up period was 9.5 months (1-25 months). The authors evaluate the
      postoperative natural vision, the resulting postoperative refraction, the
      incidence of complications and changes of endothelial cells before and after
      surgery. The resulting mean postoperative hyperopic astigmatism was +0.5 D and
      the myopic astigmatism -2.4 D. The reduction of values of hyperopic astigmatism
      was 88.9% and of myopic astigmatism 58.9%, the reduction of the spherical
      hyperopic component was 100% and of the myopic component 75%. On account of the
      stabilization of the postoperative refraction, low incidence of peroperative and
      postoperative complications and the insignificant decrease of endothelial cells
      the LASIK method is evaluated as effective.

PMID- 11225271
TI  - [Treatment of recurrent corneal erosion].
AB  - The author presents an account on 27 patients with relapsing corneal erosion 6 to
      60 months after phototherapeutic keratectomy. The results of this treatment
      confirm unequivocally that the method is safe, highly effective and relieves the
      patient rapidly and for a long period (possibly permanently) of complaints. A
      disadvantage is the high cost of the equipment.

PMID- 11225270
TI  - [Use of 5-fluorouracil in trabeculectomy].
AB  - The cytostatic 5-fluorouracil (5-FU) is used at present in the postoperative
      treatment of glaucoma. In 1993-6 we administered by the subconjunctival route at
      the Ophthalmological Clinic in Hradec Kralove 5-FU to a group of 158 eyes after
      trabeculectomy (TE). The basic indication was ingrowth of the filtration vesicle
      or a rise of intraocular tension to 20 torr and more in 148 eyes. Preventively 5
      FU was administered during operation during revisions of TE in 10 eyes. In the
      mentioned group with an unfavourable course of postoperative scar formation in
      the wound we achieved during the investigation period of two years after surgery
      normalization of the intraocular pressure to less than 16 torr without further
      treatment (we consider the value and condition without treatment as the optimal
      condition) in 37% of cases and in 81% less than 20 torr with treatment. Side
      effects of administration of 5-FU (most frequently erosion of the corneal
      epithelium were transient. For the mentioned indications 5-FU appears, being a
      cytostatic where the dosage can be exact, sufficiently safe for administration
      and it exerts an optimal effect.

PMID- 11225272
TI  - [Social rehabilitation of patients with severe visual impairment].
AB  - The author presents basic information about types of social rehabilitation of
      subjects with severely impaired eyesight in the Czech Republic. Rehabilitation is
      provided by Centres for early care, special schools, special pedagogical centres,
      Tyfloservis (to which special attention is devoted) and other centres of the
      Czech Blind United incl. contacts. A component of the paper is the whole list of
      all centers of social rehabilitation of the blind including contact. The aim of
      my paper is to summarize all the basic information concerning social
      rehabilitation of blind and people with impaired vision and to help
      ophthalmologists and their patients with impaired vision to get touch with
      concrete institute follow-up care.

PMID- 11225273
TI  - [Assessment of the nerve fiber layer in the diagnosis of glaucoma].

PMID- 11225274
TI  - [Modern trends in the genetics of ophthalmology. II. Detection of heterozygotes
      and microforms of hereditary disorders in ophthalmology].

PMID- 11225275
TI  - [Professor Vaclav Vejdovsky--the man and his work].
AB  - Professor Vaclav Vejdovsky, for many years head of the Olomouc Clinic, is a
      distinguished personality of Czechoslovak ophthalmology. He was head of the
      department for 42 years and created an important school of ophthalmology. He was
      one of the founding members of the Czechoslovak Ophthalmological Society and for
      many years its vie-chairman, in 1967-1970 its chairman. He represented
      Czechoslovakia in the committee of the European Ophthalmological Society.
      Professor Vejdovsky has special merits as regards introduction of Czech
      nomencalture into previous almost exclusively German ophthalmology in Moravia.

PMID- 11225276
TI  - Retrospective and prospective sustainable water supply use instead of
      consumption.

PMID- 11225277
TI  - Drinking water hygiene in the 21st. century--what can be done?

PMID- 11225278
TI  - 'Safe' drinking water worldwide.

PMID- 11225279
TI  - Microbiologically safe drinking water.

PMID- 11225280
TI  - Safe water supply without disinfection in a large city case study: Berlin.
AB  - Berlin's water supplies originate exclusively from groundwater. For sustainable
      water management, river water is treated by flocculation and filtration and used
      either for artificial groundwater recharge (rivers Spree and Havel) or for bank
      filtration (Nordgraben and Lake Tegel). Drinking water chlorination was abandoned
      in Berlin (West) in 1978, and in Berlin (East) in 1992, following German
      unification. Chlorine consumption for the purpose of weekly performance checks in
      the chlorination plants of Berlin's 11 waterworks and occasional chlorination
      within the pipe system following pipe burst events amounts to 2500 kg per year.
      Based on the annual water demand of 250 million cubic metres, this is equivalent
      to 0.01 mg of chlorine per litre. Microbiological monitoring at the 11 waterworks
      and at 383 sampling points within the pipe system shows CFU at less than 10/1 ml
      1 and coliforms and E. coli invariably at 0/100 ml-1. In view of the low AOX
      content, a multiplication of bacteria within the pipe system can be expected to
      occur not at all or only to a small extent. Resource protection measures, filter
      backwashing and pipe system maintenance in observance of the relevant technical
      rules will continue to ensure that the quality of Berlin's drinking water meets
      stringent hygiene requirements without chlorination.

PMID- 11225281
TI  - Disinfecting capacity and prevention of bacterial growth in the net of a long
      distance water supply system.

PMID- 11225282
TI  - UV disinfection in drinking water supplies.
AB  - UV disinfection has become a practical and safely validatable disinfection
      procedure by specifying the requirements for testing and monitoring in DVGW
      standard W 294. A standardized biodosimetric testing procedure and monitoring
      with standardized UV sensors is introduced and successfully applied. On-line
      monitoring of irradiance can be counterchecked with handheld reference sensors
      and makes it possible that UV systems can be used for drinking water disinfection
      with the same level of confidence and safety as is conventional chemical
      disinfection.

PMID- 11225283
TI  - Safe drinking water production in rural areas: a comparison between developed and
      less developed countries.
AB  - At the fundamental level, there are remarkable parallels between developed and
      less developed countries in problems of providing safe drinking water in rural
      areas, but of course, they differ greatly in degree and in the opportunities for
      resolution. Small water supplies frequently encounter difficulty accessing
      sufficient quantities of drinking water for all domestic uses. If the water must
      be treated for safety reasons, then treatment facilities and trained operating
      personnel and finances are always in short supply. Ideally, each solution should
      be sustainable within its own cultural, political and economic context, and
      preferably with local personnel and financial resources. Otherwise, the water
      supply will be continuously dependent on outside resources and thus will not be
      able to control its destiny, and its future will be questionable. The history of
      success in this regard has been inconsistent, particularly in less developed but
      also in some developed countries. The traditional and ideal solution in
      developing countries has been central water treatment and a piped distribution
      network, however, results have had a mixed history primarily due to high initial
      costs and operation and maintenance, inadequate access to training, management
      and finance sufficient to support a fairly complex system for the long term.
      These complete systems are also slow to be implemented so waterborne disease
      continues in the interim. Thus, non-traditional, creative, cost-effective
      practical solutions that can be more rapidly implemented are needed. Some of
      these options could involve: small package central treatment coupled with non
      piped distribution, e.g. community supplied bottled water; decentralized
      treatment for the home using basic filtration and/or disinfection; higher levels
      of technology to deal with chemical contaminants e.g. natural fluoride or
      arsenic. These technological options coupled with training, technical support and
      other essential elements like community commitment provide opportunities that
      should be explored both for rural small communities and in rapidly growing
      periurban areas in developing countries.

PMID- 11225284
TI  - [Branch-specific detection of phenols and assessment of ground water solubility].
AB  - There are about 500 technically relevant phenolic compounds such as cresols,
      chlorophenols or nitrophenols. It is most preferable to determine phenols as
      single compounds via gas chromatography. Further, phenols can also be assayed as
      photometrically as an overall parameter (Phenolindex): however, no conclusions
      about specific compounds can be drawn from this type of test. Also this method is
      not as reliable for an hazard assessment as gas chromatography. First, not all
      phenols, for instance resorcinol or 1-naphthol can be determined with this
      method. Second, phenolic groups in humic substances, which do not constitute a
      threat for groundwater, are determined alongside environmentally relevant phenols
      using this method. In most cases, it is possible to deduce which phenols can be
      expected in the groundwater of contaminated sites from the type of industrial
      usage, such as chlorophenols and pulp bleaching or nitrophenols and the
      production of explosives. Phenols are formed during coal combustion for instance
      at cokemanufactures or gasworks. They are important raw materials for the
      chemical industry from which resins, surfactants, pharmaceuticals, pigments,
      explosives, and stabilizers are produced. During the 80's phenol, cresols,
      nonylphenols, anisidines, aminophenols, dihydroxybenzenes, and naphthols were
      manufactured in amounts exceeding 10,000 t/a. Also, phenolic compounds are used
      as additives in many areas for example as solvents in the electric industry, in
      sawmills, papermanufacture, electroplating of metal sheets, as photographic
      developers, as textile dyes, or for the tanning of hydes. Due to the formation
      and use of phenols at industrial sites, groundwater contaminations are possible
      via infiltration through the unsaturated zone. Especially at gasworks and
      ammunition factories, groundwater contaminations with phenols have become known.
      In the vicinity of railway tracks and associated facillities contaminations due
      to the use of pesticides or mineral oils are possible. Input of phenols on
      agricultural lands can be caused by pesticides, sewage sludge or manure. The
      groundwater downstream of landfills often contains phenol, chlorophenols,
      cresols, and xylenols. The formation of phenol from other organic contaminants as
      benzene in groundwater has been reported. The potential for mobilization of
      phenols in the saturated zone can be estimated from their physical and chemical
      properties. Especially low molecular weight phenols are easily mobilized due to
      their high solubility in water and low potential for accumulation. These
      compounds are: phenol, cresols, xylenols, chlorophenols, hydroxybenzenes,
      nitrophenols, anisidines, aminophenols, anisol, 2-phenoxyethanol, and thiophenol.
      The stability of phenols under laboratory conditions varies. The complete
      mineralization depends mainly on the experimental set-up, i.e. nutrients,
      temperature, and type of inocula. The anaerobic degradation of phenols is
      generally slower than the aerobic. Phenol is readily biodegradable under both
      aerobic and anaerobic conditions. In general, the biodegradability depends on the
      type, number and position of substitutes. Phenols with nitro-, alkyl-, or
      chlorosubstitutes are more recalcitrant than phenol itself. Our biodegradability
      test show that the decomposition of alkylphenols is determined by the length and
      branching of the alcyllic chain. Phenols with high contamination potential are
      chlorophenols, xylenols, and nitrophenols. These compounds are both mobile and
      recalcitrant in the saturated zone. Phenolic compounds of a medium contamination
      risk are dichlorophenols, trichlorophenols, cresols, and phenol because they are
      mobile but less stable in groundwater. These compounds are known contaminants in
      the groundwater at gasworks, landfills, and ammunition factories. Aminophenols,
      anisidines, tert-butylphenols, ethylphenols, hydroxybenzenes, and 2
      phenoxyethanol also constite a potential hazard for groundwater; however, no
      contaminations with these compounds are known. Poisoning due to oral uptake of
      phenol contaminated ground- or drinking water have not been reported, which might
      be due to the pungent odor and taste phenolic compounds have even at very low
      concentrations (mg/L). Because of the taste problem, the German drinking water
      standard for phenols is 0.5 microgram/L. In Berlin, groundwater with phenol
      concentrations higher than 30 micrograms/L of alkylphenols or 2 micrograms/L of
      chlorophenols is considered contaminated.

PMID- 11225285
TI  - Novel techniques, standardization tools to enhance reliability of acoustic
      rhinometry measurements.
AB  - Acoustic rhinometry measurements are influenced by factors related to subject
      posture, breathing, inclination and positioning of the wavetube, leaks and
      distortion at the nostril-nose adapter connection and ambient noise. We present
      simple techniques to control these errors. Thus, gel on contoured nose adapters,
      shadow tracing to maintain posture, laser homing for wavetube alignment, are all
      integrated into a practical scheme that is easy to implement and causes minimum
      discomfort to subjects. Repeatability improved to below 3% coefficient of
      variation (CV) in non decongested subjects when trained operators used all the
      techniques together viz. gel on nose adaptors, shadow tracing, laser homing. In a
      factorial experiment, repeated measurements were made on subjects over two
      consecutive days with operator training and standardization tools as variables.
      An analysis of variance identified the most important factors to be gel on
      contoured nose adapters, operator training and control of breathing. With gel,
      the mean CV between readings was 5.8%, measurement time 30.3 seconds. The tools,
      especially gel and shadow tracing, helped untrained operators achieve performance
      levels that were more comparable with trained operators. Reproducible curves
      could be taken rapidly. Thus a significant difference of 31.2 seconds between
      untrained and trained operators reduced to 12.6 seconds using tools. These
      techniques significantly improve the reliability, speed and ease of doing
      repeated acoustic rhinometry measurements and thus the quality of data generated
      in nasal studies.

PMID- 11225286
TI  - Acoustic rhinometry and rhinomanometry.

PMID- 11225287
TI  - Acoustic rhinometry: recommendations for technical specifications and standard
      operating procedures.
AB  - This document is the result of the work and discussion of the Standardization
      Committee on Acoustic Rhinometry and presents guidelines for quality control and
      optimal application of acoustic rhinometry at its present stage. It is suggested
      that: 1. A well-defined standard nose is used for testing and optimising the
      equipment (data for a standard nose is given in the paper). 2. Procedures for
      evaluation of accuracy and repeatability of the measurements in the standard nose
      are presented, and error limits are defined for the area-distance curve as a
      whole, for the minimum cross-sectional area and for the volume from 0-5 cm into
      the nose. 3. Publication of results should include the volume 0-5 cm into the
      nose (volume from 2-5 cm for mucosal changes) the minimum cross-sectional area or
      preferably the two first minima and the distances to those areas. 4. The operator
      should be trained, follow a standard operating procedure and the environmental
      conditions (temperature and noise) be controlled. 5. Attention should be given to
      the nosepiece and the coupling between the equipment and the nose to obtain
      correct position, and sufficient seal without disturbing the anatomy. 6. The
      manufacturer should give information about the performance of the equipment,
      calibration procedures and maintenance, hygiene, environmental and safety
      standards.

PMID- 11225288
TI  - Clinical applications of acoustic rhinometry.
AB  - The clinical value of acoustic rhinometry (AR) is its ability to measure the
      dimensions of the nasal cavity in terms of a curve describing the cross-sectional
      areas as a function of distance. This curve describes nasal airway patency and
      gives an impression of the degree of nasal obstruction. The method provides
      values before and after decongestion which allow to evaluate the cause of the
      nasal obstruction as mainly skeletal or mucosal. This makes AR a tool for
      diagnosis and follow-up of treatment in both rhinology and rhinosurgery.
      Similarly, AR is a reliable method to show the dimensional changes of the nasal
      cavity before and after a given treatment. In the evaluation of a surgical
      intervention it is reasonable to use decongested values. Turbinate surgery, septo
      and rhinoplasty, orthognatic surgery and paranasal sinus surgery and their
      influence on the dimensions of the nasal cavity may be reflected by AR. The
      absolute minimum cross-sectional area, and cross-sectional areas and volumes at
      fixed distances are the recommended parameters to show dimensional changes after
      nasal surgery. The predictive value of AR, in relation to nasal obstruction,
      should have high specificity and sensitivity to be used in a clinical setting. It
      seems that the single variables do not provide enough information for the
      diagnosis of obstruction, and it has been stressed that the results should be
      interpreted together with rhinoscopy and subjective complaints. A statistical
      model based on questionnaire, rhinoscopic findings and several variables from AR
      has been proposed to increase the diagnostic specificity and sensitivity of AR.

PMID- 11225289
TI  - Nasal histamine challenge: a reproducible model of induced congestion measured by
      acoustic rhinometry.
AB  - We describe the development of a clinical model of nasal congestion using a fixed
      dose histamine challenge in normals. The objective was to use histamine to induce
      a similar degree of nasal congestion as a natural common cold (from unpublished
      data of 250 cold sufferers) and thus establish a rapid screening system for
      decongestant drug effects. Sixtynine normal subjects were challenged with
      histamine diphosphate (300 micrograms/nostril) on 2 visits. Thirtytwo subjects
      were identified showing reproducible baseline values (< 15%CV (coefficient of
      variation)) and adequate nasal congestion (minimum 20%) without excessive
      sneezing. Reproducibility was evaluated in them post challenge using acoustic
      rhinometry and rhinomanometry. Twentythree subjects showed a variation < 25%CV of
      nasal volume over multiple visits in a 5 month period. The average reduction in
      nasal volume and airflow 15 minutes post challenge was 32% and 41% respectively.
      Acoustic rhinometry values were less variable than rhinomanometry values.
      Negligible differences (< 2%) in histamine response over visits and similar
      correlation between measured values at first, second and last visits indicate
      that 2 visits are adequate to evaluate response reproducibility in a selected
      population. We conclude that it is feasible to develop a robust clinical model of
      nasal congestion using histamine.

PMID- 11225290
TI  - Acoustic rhinometry in infants and children.
AB  - Acoustic rhinometry (AR), introduced a decade ago for assessment of the nasal
      airways of adults, has several attractive features relevant to application in a
      paediatric population. Its non-invasive nature, simplicity and rapidity are prime
      assets when examining infants and small children. Valid AR measurements can be
      obtained in a few seconds and require minimal co-operation. The striking
      consistency of AR studies of healthy subjects and the agreement with CT-derived
      and directly measured choanal dimensions are a strong indication of its
      reliability. Acoustic rhinometry optimised for infants and small children opens
      new perspectives and possibilities in the assessment of nasal airway dimensions
      and their relationship to pathological conditions in both the upper and the lower
      airways. The objective of this paper is to describe the advantages of AR in
      infants and children, but also point out its limitations and potential sources of
      error. Practical guidelines as to the measurement procedure and analysis and
      interpretation of AR-data are outlined.

PMID- 11225291
TI  - Acoustic rhinometry in epidemiological studies--nasal reactions in Swedish
      schools.
AB  - A cross-sectional study was performed on the relationships between hygienic
      measurements and nasal investigations in 234 personnel in 12 primary schools in
      mid-Sweden. Hygienic data included building characteristics, measurements of
      indoor air pollutants, air change rate, temperature and humidity. Clinical
      examinations included symptom reports, acoustic rhinometry and nasal lavage, with
      the determination of biomarker levels for eosinophil cationic protein (ECP),
      lysozyme, myeloperoxidase (MPO) and albumin. Subjective nasal obstruction was
      increased in schools with mechanical ventilation (adjusted prevalence OR = 2.0;
      95 CI 1.1-3.7) and subjects reporting nasal obstruction had higher levels of dust
      in the classroom, compared to those not reporting this symptom (p = 0.008 by Mann
      Whitney U-test). Congruently, a decreased nasal patency measured by acoustic
      rhinometric minimum cross-sectional areas (MCA1 and MCA2) was related to the use
      of mechanical ventilation (p = 0.008 and p = 0.02 respectively, by Mann-Whitney U
      test), dust levels (p = 0.03 and p < 0.001 respectively, by Kendall's tau
      correlation analysis), a lower cleaning frequency of desks (p < 0.001 and p =
      0.02 respectively, by Kendall's tau correlation analysis), the use of wet mopping
      (p < 0.001 and p = 0.04 respectively, by Mann-Whitney U-test) and PVC floor
      material (p < 0.001 and p = 0.034 respectively, by Mann-Whitney U-test). The
      cleaning frequency of floors was positively correlated with MCA1 (p = 0.049 by
      Kendall's tau correlation analysis). In buildings with signs of water damage,
      flat roof or a concrete slab fundament the personnel had increased ECP, lysozyme
      or albumin levels in nasal lavage. A reduced nasal patency and an increased
      inflammatory biomarker response were seen for higher levels of formaldehyde
      (MCA1, MCA2, VOL1, VOL2, ECP and lysozyme) and nitrogen dioxide (MCA1, VOL2, ECP
      and lysozyme) in the classrooms. In conclusion, the results indicate that
      acoustic rhinometry in combination with the determination of nasal lavage
      biomarkers can be used to study effects on the upper airways of the indoor
      environment. Actual exposures to indoor air pollutants in Swedish schools can
      affect the occurrence of subjective nasal obstruction and give clinical signs of
      reduced nasal patency together with an inflammatory biomarker response in the
      nasal mucosa.

PMID- 11225292
TI  - Rethinking physiologic stability: touch and intracranial pressure.
AB  - The purpose of this research was to examine the contingent nature of physiologic
      stability with respect to the impact of nursing and parental care touch on
      intracranial pressure (ICP) in children. Data were reanalyzed from those
      previously collected in eight children in a pediatric intensive care unit who had
      intracranial hypertension from a variety of causes and whose ICP was invasively
      monitored. One hundred forty-nine clusters of spontaneous touch/talking were
      available for analysis after those occurring close in time to procedures and
      drugs affecting ICP were dropped. Twenty-three episodes of investigator touch
      (without talking) were also analyzed. ICP stability was defined as any tracing
      over a defined time period in which the peak-to-trough amplitude did not exceed
      twice the calculated resting variability. Such an approach allowed classification
      and counting of stable versus unstable baselines, and stable versus unstable
      responses to touch. Therefore, ICP stability was examined by comparing the
      stability of the ICP tracing the last minute prior to a cluster of nonprocedural
      touch (baseline) with the first minute after the cluster. Clusters of spontaneous
      touch were nearly always associated with talking to the child and rarely were
      followed by change in level of ICP greater than that child's ICP variability at
      rest. Investigator stroking without talking never was followed by a significant
      change in level of ICP. There was a contingent relationship between stability of
      the ICP tracing prior to a cluster of touching/talking such that the probability
      of ICP becoming more stable when the touch/talk occurred on an unstable baseline
      was twice that of touch/talk occurring on an stable baseline.

PMID- 11225293
TI  - Insulin increases sodium (Na+) channel density in A6 epithelia: implications for
      expression of hypertension.
AB  - Essential or primary hypertension is a multifactorial disease that is expressed
      as a result of complex interactions between genes and environmental influences.
      Several mutations in many different proteins are associated with expression of
      hypertension, including abnormalities in the epithelial sodium channel (ENaC)
      found in absorptive organs (i.e., distal colon, distal tubule of the nephron).
      Some of these mutations result in structural and/or functional alterations in
      ENaC-mediated Na+ entry in epithelia responsible for fluid and electrolyte
      balance and are associated with expression of hypertension. Studies support the
      notion that there is a link between ENaC and hypertension of both the monogenic
      (single gene mutation) and primary or essential type (a multifactorial disease).
      Alterations of other aspects of the environment of absorptive cells (e.g.,
      hyperinsulinemia, hyperaldosteronemia, high plasma cortisol, high plasma Na+)
      have also been shown to elicit hyperabsorption of Na+ via ENaC and therefore
      could contribute significantly to expression of hypertension in people with
      intermediate phenotypes. This article describes an initial study in which the
      effects of an environmental factor, extracellular levels of insulin, on ENaC were
      examined in a normal kidney cell model. Electrophysiologic techniques revealed
      that ENaC density rapidly increased in response to addition of insulin to the
      basolateral bath. This autoregulatory recruitment of Na+ total channel density
      masked a slight decrease in open channel probability. Insulin's effect on ENaC
      function and implications on fluid and electrolyte balance and expression of
      primary hypertension is discussed.

PMID- 11225294
TI  - Dehydration: biological considerations, age-related changes, and risk factors in
      older adults.
AB  - Maintenance of water balance is essential to normal physiologic function and
      vigorous aging. Older adults, however, frequently experience alterations in fluid
      homeostasis, which result in dehydration. This article describes the physiology
      of water balance, age-related changes that influence fluid regulation, and
      associated risk factors for dehydration in older adults. Fluid hygiene is an
      important health promotion activity for this age group, but when efforts to
      prevent imbalance are unsuccessful, early identification and intervention to
      correct problems should be done to minimize adverse consequences. Although much
      is known about fluid homeostasis, dehydration, and contributory factors in the
      aging process, water disorders remain prevalent in this group. A great deal of
      work is still needed to determine "best practices" and creative clinical
      interventions to support adequate fluid intake behaviors. Both quality management
      programs and research studies provide avenues for systematic evaluation.

PMID- 11225295
TI  - Spatial patterns of atrophied muscle fibers during exercised recovery.
AB  - The effect of run training during the recovery period on the spatial
      distributions of fiber type was examined in atrophic soleus muscle of adult rats
      following 28 days of hindlimb suspension. During recovery, clusters of damaged
      and type IIC fibers were observed, which were more pronounced in the exercised
      animals than in both exercised and nonexercised control groups. The results
      indicate that exercise during recovery following suspension-induced hindlimb
      muscle atrophy produces changes in the soleus fiber-type cross-sectional area,
      both absolute and relative. These changes were not seen in the sedentary recovery
      group or in control rats exposed to the same exercise regimen. The author
      concludes that this treatment, unlike neurogenic pathologies, does not cause any
      remodeling during recovery, in the sense of changed adjacency relations among
      fiber types.

PMID- 11225296
TI  - Recovery of plantaris muscle from impaired physical mobility.
AB  - The purpose of this investigation was to describe and compare various methods of
      recovering atrophied fast-twitch skeletal muscle following long-term impaired
      physical mobility. An animal model was used to study morphological adaptations of
      atrophied plantaris muscles to the effects of 28 days of hindlimb suspension (HS)
      followed by either sedentary recovery or run training during a 28-day recovery
      period. Significant atrophy, demonstrated by decreased mean fiber area (MFA,
      micron 2), occurred during the 28-day period of HS. However, run training
      following long-term atrophy induced by HS did not result in the high levels of
      frank muscle damage and type IIC fibers previously reported in slow-twitch soleus
      muscle following long-term (28 days) atrophy.

PMID- 11225297
TI  - Effect of aerobic fitness on the physiological stress response in women.
AB  - Stress reactivity was assessed in aerobically fit (n = 14) and unfit (n = 8)
      females during the follicular phase of the menstrual cycle. Participants
      completed the Spielberger State-Trait Anxiety Inventory and provided a urine
      sample for catecholamine analysis before and after mental stress testing, Stroop
      Color-Word Test. Blood pressure, heart rate, muscle tension, and skin conductance
      were measured during mental stress testing. Fit and unfit participants differed
      significantly in baseline heart rate but not in stress reactivity or in state or
      trait anxiety. These data suggest that aerobic fitness does not attenuate the
      stress response in women prior to menopause.

PMID- 11225298
TI  - Isokinetic strength testing in research and practice.
AB  - Age-related losses in lower extremity strength result in functional disabilities
      that diminish the quality of life for many older adults. Multiple factors,
      including type of muscle fiber, size of the muscle, length and speed of the
      muscle at contraction, age, and gender, affect the magnitude of strength
      generated. Assessment in clinical practice, in order to be cost and time
      effective, screens older adults for loss in strength. Further evaluation of
      strength loss requires the use of sophisticated procedures and equipment.
      Research into the causes of loss of strength and interventions to lessen or
      prevent loss of strength requires valid and reliable assessment tools. This
      article examines components of isokinetic muscle strength, the measurement of
      strength in clinical practice, methods to measure isokinetic strength, and
      validity and reliability of these measures.

PMID- 11225300
TI  - [Influenza surveillance and control program of WHO].
AB  - The World Health Organization(WHO) influenza surveillance network now maintains
      110 National Influenza Centers in 83 countries and four WHO Collaborating
      Centers(London, Atlanta, Melbourne and Tokyo). This network provides useful
      epidemiological and virological information to decide the recommended vaccine
      composition each year. Another important role of the network is to detect and
      analyze potential pandemic strains, since an early detection of pandemic strain
      is crucial to minimize the impact of the pandemic. WHO continues to improve the
      global surveillance particularly in China, since China has the important role for
      the influenza epidemiology in the world. WHO also published Influenza Pandemic
      Preparedness Plan in 1999.

PMID- 11225299
TI  - Serum prolactin in breastfeeding: state of the science.
AB  - Prolactin is one of two major hormones involved in lactation. While the role of
      infant suckling and oxytocin in the lactation process are well understood, the
      role of prolactin is less clear. A variety of factors related to prolactin have
      been investigated, and these are used as an organizing framework for this
      article. Factors include pregnancy, lactation, nursing frequency, prior lactation
      experience, milk production, and pharmacologic agents. The literature, while
      substantial in amount, presents inconsistencies. Implications for practice are
      discussed.

PMID- 11225301
TI  - [Influenza epidemics and their evaluation].
AB  - Influenza has a typical seasonal outbreak pattern during the winter in Japan.
      During this period, a number of information on influenza is available through
      many institutions including the Ministry of Health and Welfare(MHW). The
      information is collected through different systems for different purposes.
      Therefore the information required different interpretation. Using the
      information systems of the MHW as an example, the point for interpretation and
      the limitation for these data sets are analysed.

PMID- 11225302
TI  - [Morbidity and mortality of influenza in Japan].
AB  - Influenza is reportable in Japan since 1947. The current sentinel surveillance
      system for influenza started in 1987. Influenza morbidity is clearly correlated
      with increased influenza and pneumonia mortality and mortality from other major
      underlying diseases, which results in an increased overall mortality. The
      expected mortality was calculated from a seasonal ARIMA model for influenza and
      pneumonia. Excess mortality is defined as the number of deaths exceeding the
      upper confidence limit that was calculated from the model. During the 1998/1999
      season, the estimated number of excess deaths from pneumonia and influenza was
      about 10,000 and from all causes about 40,000. More than 90% of these deaths
      occurred among elderly.

PMID- 11225303
TI  - [Problems of influenza immunization and it's future].
AB  - Influenza killed vaccine were used all over the world. In Japan originally used
      for the children at elementary school and middle school. The purpose is that
      these age are frequent contact of each other and they bring back to their home
      influenza virus. However there are many opinion against efficacy of influenza
      vaccine. Then Ministry Health and Welfare decided that influenza vaccine should
      be use as a optional vaccine. At that time, we recommended that the high risk
      group should continue this vaccine. Recently, Japanese old age people lives in
      old-people's home. New problems comes up, how to protect them from sever
      influenza infection and complications. From our data, it is better to continue
      influenza vaccine once a year.

PMID- 11225304
TI  - [Mechanisms of antigenic variation in influenza virus].
AB  - Human influenza A viruses evolve rapidly by antigenic shift and antigenic drift.
      Antigenic shift occurs by genetic reassortment between currently circulating
      human viruses and influenza viruses of other origin, by re-emergence of a
      previously circulating virus, and by invasion of animal influenza viruses. The
      segmental structure of the virus genome enables reassortment in multiply infected
      cells and also promotes multiple infection because it results in yielding
      noninfectious particles which randomly lack some genome segment and only become
      infectious by complementation with others. Antigenic drift is due to an
      accumulation of nonsynonymous substitutions in the genes encoding the HA and NA
      proteins. The limited nature of infection to the respiratory epithelium which is
      the border of the immune system enables the virus to reinfect and grow under the
      partial immune pressure which results in selecting and expanding antigenic
      mutants.

PMID- 11225305
TI  - [Receptor sialylsugar chains as determinants of host range of influenza viruses].
AB  - All types of the hemagglutinin(HA) of human, pig, horse and aq. bird influenza A
      viruses, recognize sialyl lacto-series type I and II sugar chains(Sialic acid(SA)
      alpha 2-3(6)Gal beta 1-3(4) GlcNAc beta 1-) in glycoproteins and glycolipids in
      the target cells as common receptor molecules. Avian and equine influenza viruses
      preferentially binds the terminal sialic acid alpha 2-3Gal(SA2-3Gal) linkage,
      while human influenza viruses preferentially bind the SA2-6Gal linkage. SA
      distribution in animal species influence influenza virus host range. Swine
      trachea has both receptors for avian influenza viruses (SA2-3Gal specific) and
      for human influenza viruses(SA2-6Gal specific). In the case of horses, a virus
      with an HA recognizing Neu5Ac2-6Gal, but not Neu5Ac2-3Gal, failed to replicate in
      horses, while one with an HA recognizing the Neu5Gc2-3Gal moiety replicated in
      horses. The abundance of the Neu5Gc2-3Gal moiety in epithelial cells of horse
      trachea supports that recognition of Neu5Gc2-3Gal moiety is critical for viral
      replication in horses. The Neu5Gc2-3Gal is also associated with viral replication
      in duck intestine, primarily in the crypt epitherial cells. Such recognition,
      together with biochemical evidence of Neu5Gc in crypt cells, correlated exactly
      with the ability of the virus to replicate in duck colon. These results indicate
      the evidence of biologic effect of different sialic acid species in different
      animals.

PMID- 11225306
TI  - [Pathophysiological events in the central nervous system of mice during
      neurovirulent influenza A virus infection].
AB  - Influenza A/WSN/33 virus inoculated into the olfactory bulb of C57BL/6 mice
      selectively infects the anterior olfactory nucleus, habenular, paraventricular
      thalamic, and brainstem monoaminergic neurons. Infected neurons died by day 12
      with perforin-mediated neuroapoptosis, that appears significant to exterminate
      the intracellular pathogen in the early stage of infection. In perforin-deficient
      mice virus infection continued for a longer period of 35 days. Activated
      microglial cells with overexpression of the Iba1 appeared widespread in the
      brain, participating in the protection, maintenance, and repair of infection
      spared neurons. Macrophages accumulated in virus-infected areas to expedite the
      resolution of the virus infection.

PMID- 11225307
TI  - [Mechanism of the emergence of pandemic influenza virus strains and their control
      measures].
AB  - The 1957 Asian H2N2 and 1968 Hong Kong H3N2 pandemic strains of influenza are
      genetic reassortants between avian viruses and human strains. Since avian viruses
      of any subtype can contribute genes in the generation of reassortants in pigs,
      none of the 15 HA and 9 NA subtypes can be ruled out as potential candidates for
      future pandemics. The H5N1 influenza virus transmission from domestic poultry to
      humans in Hong Kong in 1997 further emphasized the need to have information on
      influenza viruses in avian species. For the prediction and control of future
      pandemics, the program of global surveillance of animal influenza has been
      started. Influenza virus isolates from animal species should be thoroughly
      characterized and be provided for the use of diagnosis and vaccine preparation.

PMID- 11225308
TI  - [Detection of influenza virus by RT-PCR].
AB  - RT-PCR is the sensitive and rapid diagnostic method of influenza virus infection.
      Using appropriate primers, RT-PCR is capable of detecting and typing or subtyping
      of influenza A and B viruses simultaneously from a clinical specimen. Compared
      with virus culture in MDCK cells, Little or no increase has been observed in
      detection rate of influenza viruses in respiratory tract-derived specimens. The
      procedure is valuable, however, in dealing with specimens containing
      predominantly inactivated virus(as a result of prolonged storage) as well as
      those that may contain very few infectious viruses(e.g. cerebrospinal fluid and
      blood). Even in these cases, however, it is preferable that RT-PCR is made in
      combination with other traditional, diagnostic methods.

PMID- 11225309
TI  - [Rapid diagnosis of influenza by EIA].
AB  - There are several commercially available rapid tests by enzyme immunoassay for
      the laboratory diagnosis of influenza. The tests detect viral nucleoproteins with
      monoclonal antibodies. They are less sensitive than viral culture or PCR, but
      rapid and easy to perform, so they can be used at the point-of-care. We evaluated
      these kits and compared them with viral culture, and we concluded that they are
      reliable. When compared with viral culture, the sensitivity of the EIA tests with
      nasal specimens showed greater than 80%. EIA was more sensitive in detecting
      influenza viruses in nasal aspirates and nasal swabs than in throat swabs. The
      rapid detection kits facilitate the timely initiation of antiviral therapy and
      control of influenza outbreaks in institutions. They are clinically useful and
      cost-effective for the diagnosis of influenza.

PMID- 11225310
TI  - [The rapid detection kit based on neuraminidase activity of influenza virus].
AB  - The ZstatFlu test(ZymeTx, USA) is a rapid detection kit for influenza types A and
      B virus. This test is based upon the reaction between viral neuraminidase from
      influenza viruses and chromogenic substrate. The positive specimen of influenza
      type A or B virus cleave the substrate and produce a blue colored product. The
      ZstatFlu was evaluated by a prototype viruses, isolated viruses and clinical
      specimens. At result, this kit was reactive for all human influenza type A and B
      virus. No cross reactivity was detected with other respiratory viruses, including
      parainfluenza type 1, 2, 3 and mumps viruses with neuraminidase activity. Throat
      swabs were used for the test. By comparison with cell culture and RT-PCR. The
      sensitivity and the specificity was 77.0% and 90.2% respectively. The ZstatFlu
      should be useful for the rapid diagnosis of influenza virus infection.

PMID- 11225311
TI  - [Clinical features of influenza in children].
AB  - All age groups in a population become ill with fever, respiratory tract
      involvement and systemic symptoms by influenza A virus. An understanding of the
      differences in the clinical features of influenza between children and adults may
      be helpful for the diagnosis and the treatment of influenza in children. This
      paper summarizes the clinical features and the disease burden of influenza in
      children, the currently available rapid diagnosis kits for influenza A and B
      virus, the treatment of influenza A and B infections by anti-influenza
      medications(amantadine and zanamivir), the prophylaxis of influenza A and B
      infections by anti-influenza medications and vaccines, and the prognosis.

PMID- 11225312
TI  - [Clinical features of influenza in the aged].
AB  - Influenza is a serious disease for the elderly. Influenza causes high fever in
      the elderly, similar as in healthy adults. Cough lasts longer, but frequency and
      degree of sore throat and coryza is lower in the elderly. Rapid diagnosis kits
      based on enzyme-linked immunoassay contribute to quick diagnosis, improving
      treatment of the elderly. Amantadine can mitigate various symptoms and hastens
      recovery. Other newly developed neuraminidase inhibitors are also hopeful for
      treatment. The poor prognosis of influenza in the elderly is associated with a
      high frequency of pneumonia complications. Decreased serum albumin level is a
      risk factor for post-influenza pneumonia. To reduce excess influenza death in the
      elderly, prophylaxis and management of the general health condition of elderly
      patients may be most important.

PMID- 11225313
TI  - [Pneumonia and influenza].
AB  - Pneumonia is more frequent in the elderly and results in higher mortality.
      Primary viral pneumonia is not so common but important in severe cases. Chest X
      ray shows grand-glass appearance or linear shadow in pure viral pneumonia cases.
      That is sometimes specific and clearly different from consolidation or
      infiltration with bacterial pneumonia. We can try to decrease pneumonia and
      influenza mortality, if we prevent influenza infections by vaccination and treat
      by anti-influenza drugs. Secondary bacterial pneumonias are more common, caused
      by such as Streptococcus pneumonia, Hemophilus influenzae, Branhamella
      catarrhalis. Gram staining and the culture of purulent sputum was useful for
      treatment by antibiotics.

PMID- 11225314
TI  - [Influenza-associated encephalitis/encephalopathy in childhood].
AB  - Influenza-associated acute encephalitis/encephalopathy in childhood was reviewed.
      Annual incidence of this disease condition is estimated as 100-500 cases in
      Japanese children. Mortality rate of this disease would be as high as 40% died
      with a rapid fulminant course. Coagulopathies, hepatic dysfunctions and brain CT
      abnormalities were risk factors for the poor prognosis. The destruction of the
      vascular endothelial cells via the activation of inflammatory cytokines by
      influenzavirus would presumably be the pathomechanism of the neurological
      dysfunction.

PMID- 11225315
TI  - [Reye's syndrome].
AB  - A nationwide survey on Reye's syndrome(RS) was described. And problems between RS
      and influenza virus such as etiology, pathophysiology, differential diagnosis and
      epidemiology were reviewed. So-called aspirin issue on RS was re-evaluated
      according to recent advance of RS research. Finally future aspect of Reye's
      syndrome was also discussed.

PMID- 11225316
TI  - [Influenza myocarditis].

PMID- 11225317
TI  - [Myositis and rhabdomyolysis with influenza infection].
AB  - Myositis and rhabdomyolysis with influenza are rare, but sometimes serious
      complications. Patients with myositis more commonly have influenza B infection
      than influenza A. On the other hand, rhabdomyolysis are more frequently
      recognized in patients with influenza A infection than those with influenza B.
      Upper respiratory symptoms usually precede myositis, while rhabdomyolysis occurs
      simultaneously or shortly after the respiratory symptoms. Creatine kinase levels
      are elevated in myositis mildly and in rhabdomyolysis markedly. Influenza
      myositis improve spontaneously within 6 weeks, but influenza rhabdomyolysis
      sometimes induce renal failure with fatal outcome. Although the true incidence of
      myositis and rhabdomyolysis in the influenza infection remains unknown, careful
      medical care is necessary when patients have muscle pain and weakness.

PMID- 11225318
TI  - [Antiinfluenza-drugs and the standard of the use].
AB  - Amantadine is only effective for influenza A, but zanamivir and oseltamivir,
      neuramidase inhibitors are strongly effective for influenza A and B. At this time
      we are available for amantadine and zanamivir for influenza in Japan. Oseltamivir
      is now under investigation in Japan. In USA both new drugs have been approved by
      USA government. Influenza vaccine is the first line drug for prevention of
      influenza A and B. In cases influenza infection occurs, we should promptly select
      and give antiinfluenza drug for these patients during almost 5 days, considering
      renal condition. And we should keep in mind that these antiviral substances are
      not directly effective for inflammatory phenomenons which introduce the reduction
      of lung function. So we should use both therapies which include antiviral
      chemotherapy and serious rescue treatment for respiratory failure.

PMID- 11225319
TI  - [Anti-influenza A viral drug--amantadine].
AB  - Amantadine, an inhibitor of M2 ion channel of influenza A virus, is an oral
      antiviral drug which specifically inhibits the uncoating and viral replication of
      the influenza A virus. Studies have shown that amantadine treatment within 48
      hours of acute infection of influenza A reduces fever within 24 hours and
      shortens the course of illness. Amantadine has been found to have an efficacy of
      50 to 90% prevention of illness. However amantadine-resistant viruses have been
      recovered approximately 30% patients treated with amantadine, as early as 2-3
      days into treatment. Side effects of insomnia, decreased concentration and
      dizziness have been reported in 5 to 33% of amantadine recipients. Therefore
      amantadine should be only used for influenza A infected high risk persons.

PMID- 11225320
TI  - [Neuraminidase inhibitor].
AB  - Amantadine, effective to influenza A virus, is now widely used in Japan. Recently
      new anti-influenzal agents, neuramidase inhibitor has been developed. Both
      Zanamivir (inhaled type) and Oseltamivir(oral use), are proved to be effective in
      treatment of influenza A and B. Mechanism of action on influenza virus, dosage,
      side effects of the anti-influenza agents are described. Clinicians expect to
      medicate to influenza with the agents as soon as possible.

PMID- 11225321
TI  - [Current research status of anti-influenza chemotherapy].
AB  - Current progress in anti-influenzavirus chemotherapy has lead us to clinical use
      of amantadine and NA inhibitors such as zanamivir and oseltamivir. In order to
      overcome the problems of resistant virus which may appear for these drugs, we are
      in demand to develop new anti-influenza drugs which have other target points than
      uncoating or NA activity of the virus. Several compounds under investigation
      which inhibit conformational change of HA under low pH, endonuclease activity to
      provide cap of m-RNA, antisense oligonucleotide stable for digestion by
      endonuclease, artificially synthesized Zn-finger motif peptide etc were reviewed.

PMID- 11225322
TI  - [Influenza live attenuated vaccine].
AB  - Inactivated influenza vaccine has been widely used; however, its effectiveness is
      not always perfect. To create a much better vaccine, live vaccines have been
      extensively investigated. Among several candidate live vaccines, cold-adapted(Ca)
      vaccine is the only promising candidate. According to clinical studies recently
      conducted in the U.S., Ca vaccine was proven to be highly effective against
      laboratory confirmed influenza, both in adults and children. Furthermore, Ca
      vaccines for the H5N1 pandemic strains were generated and their attenuation and
      efficacy were confirmed in experimental animals.

PMID- 11225323
TI  - [Protection against influenza by genetically engineered vaccines].
AB  - Viral vector recombinant DNA vaccines, so called genetically engineered vaccines,
      are introduced directly into cells to induce an antigen specific immune response.
      This is a new approach to vaccination that represents a new concept in
      immunotherapy, which attempts to induce a long-term effective, anti-specific,
      viral antigen immune response. These vaccines may also prove more potent than
      currently used vaccines when it comes to inducing cellular immune responses in
      addition to humoral immune response. In the case of influenza, an immune response
      with humoral characteristics was induced using an influenza hemagglutinin(HA) DNA
      vaccine. On the other hand, injection of influenza virus nucleoprotein(NP)
      induced a Th-1 type cellular immune response including CTL. Genetically
      engineered vaccines have the potential to effectively overcome the problem of
      unresponsiveness to currently used vaccines.

PMID- 11225324
TI  - [Development of influenza vaccines against pandemics].
AB  - Influenza vaccine plays a crucial role as an effective measure for control of
      worldwide influenza pandemics. Currently licensed inactivated influenza vaccines
      can be used for the pandemic situation. Surveillance to isolate animal influenza
      viruses as vaccine candidate strains greatly contributes to the rapid production
      of vaccine. The reverse genetics approach can afford to attenuate a highly
      virulent virus by genetic engineering of any viral genes for the use of vaccine
      strain. The other approach to develop influenza vaccine should be encouraged to
      overcome the disadvantage of currently used inactivated vaccine.

PMID- 11225325
TI  - [Prevention and care management of influenza infection in institutions for the
      elderly and high risk groups].
AB  - Influenza infection is a serious problem in institutions for the elderly and
      those with increased risk factors because of the high pneumonia complication rate
      and a significant increase in mortality. An outbreak of influenza is mainly
      caused by contact from the staff to residents, therefore the health care of the
      staffs and prevention of influenza should be a high priority in institutions such
      as nursing homes. To prevent influenza epidemics, institutionalised elderly and
      high risk groups should be vaccinated more actively. The rapid test for diagnosis
      of influenza viral infection permits the timely administration of antiviral
      agents and infection control among institutionalised elderly and high risk
      groups. Amantadine and neuraminidase inhibitors could be used for treatment and
      prophylaxis of influenza among institutionalised elderly and high risk group
      patients.

PMID- 11225326
TI  - [Mild brain hypothermia for influenza encephalitis/encephalopathy and its
      significance].
AB  - During the Winter or Influenza season in Japan, there has been an increase in the
      number of patients presenting with Central Nervous System complaints or symptoms.
      One of the causes is reported be Influenza encephalitis/encephalopathy. Some of
      these patients undergo a course of Reye's Syndrome, Acute Necrotizing
      Encephalopathy (ANE), or Hemorrhagic Shock and Encephalopathy(HSE), of which the
      pathologic features are still unknown. It is likely that the major underlying
      feature is cerebral edema, caused by impairments in the blood-brain barrier,
      which is mediated by inflammatory cytokines. Mild brain hypothermia may be an
      effective treatment in preventing cerebral edema by preventing the cytokine
      activation and elevations in brain temperature. A combination of mild brain
      hypothermia and high-dose corticosteroid therapy is thought to be effective in
      the treatment of influenza encephalitis/encephalopathy.

PMID- 11225327
TI  - [Toxic shock syndrome complicating influenza].
AB  - In January 1999, an outbreak of type A(H3N2) influenza occurred in a psychiatric
      hospital. Among 273 inpatients, 59 male and 40 female patients, age between 24-84
      year old, developed high fever(38 degrees C), joint pain, cough and nasal
      discharge, and eleven male and one female patients died. In that hospital,
      Methicillin-resistant Staphylococcus aureus(MRSA), with production of toxic shock
      syndrome toxin-1 (TSST-1) and staphylococcal enterotoxin(SE) type C(SEC), were
      isolated from inpatients, medical stuffs and hospital environments. Under
      investigation, a 59-year-old male inpatient developed respiratory failure
      following influenza infection. The titer of serum TSST-1 antibody and SEC
      antibody of this patient was significantly elevated in his clinical course. It is
      highly suspected that influenza outbreak occurred among MRSA carriers and TSS was
      complicated with fatal cases.

PMID- 11225328
TI  - [Gastroenterology--endoscopy].

PMID- 11225329
TI  - [Synthetic glucocorticoid therapy--recent progress].
AB  - Synthetic glucocorticoids are administered systematically in the treatment of a
      large number of nonendocrine and endocrine diseases. Efforts have been made to
      reduce the side effects and to increase the pharmacological effects of these
      glucocorticoids. To avoid complications compartmental administration(topical,
      inhaled, suppository, ophthalmic, intra-articular) and alternate-day
      administration of intermediate acting glucocorticoids are recommended. Careful
      monitoring of the patients under therapy and gradual reduction of glucocorticoids
      should be performed to avoid adrenal insufficiency or reactivation of the
      disease. The understanding of molecular mechanisms of glucocorticoid actions may
      lead to the development of novel glucocorticoids, which are more active in anti
      inflammatory actions than endocrine and metabolic actions(adverse effects of
      glucocorticoids).

PMID- 11225330
TI  - Managed care and e-health.

PMID- 11225331
TI  - A cure in search of symptoms? Application hosting for healthcare providers.

PMID- 11225332
TI  - Psychotherapy online.

PMID- 11225333
TI  - Cyber credentialing. Software, the Internet and outsource suppliers streamline a
      once grueling process.

PMID- 11225334
TI  - Admission to discharge. Tracking a patient's progress using wireless bar coding.

PMID- 11225335
TI  - The pediatric promise. Telemed gives northern California hospital 24-hour access
      to pediatric specialists.

PMID- 11225336
TI  - Support: the most important issue? The ratio of customers to support staff is a
      critical issue.

PMID- 11225337
TI  - So many systems, so little communication. How a mega-HMO made the transition to a
      single source for financial applications.

PMID- 11225338
TI  - Planning an HR system merge. Preparation is the key to smooth integration.

PMID- 11225339
TI  - Lightning-speed certifications. Insurer cuts certification turnarounds by 60
      percent and saves $250,00 per year with Internet technology.

PMID- 11225340
TI  - What works. Better buying online. Group practice enjoys the benefits of materials
      management and inventory control.

PMID- 11225341
TI  - Managed care HotList.

PMID- 11225342
TI  - Building a filmless department. Physician practice streamlines care and cost
      through PACS.

PMID- 11225343
TI  - I'm not a doctor. I just play one on the Internet.

PMID- 11225344
TI  - Measure the impact. Research Web tools that provide opportunity for shared
      decision-making.

PMID- 11225345
TI  - Linking business value to IT investments.

PMID- 11225346
TI  - The rules are out. A middle ground has been successfully achieved.

PMID- 11225348
TI  - Aggressive acid control: minimizing progression of Barrett's esophagus.
AB  - Barrett's esophagus (BE) is a change in the cellular structure of the lower
      esophagus believed by many to be caused by frequent acid exposure. The condition
      is troublesome because of a tendency toward cell proliferation, dysplastic
      transformation, and cancerous changes within the lesions. It is speculated that
      the pronounced increase in esophageal adenocarcinoma during the past 25 years may
      be attributable to acid reflux and associated BE. Strict acid control may cause
      lesion regression in these patients. However, pH monitoring to confirm adequate
      acid control is essential, and more than 1 drug may be needed to achieve adequate
      acid control and manage many patients. More research is needed to determine
      whether aggressive acid control reduces the dysplasia and cancer risk associated
      with BE.

PMID- 11225347
TI  - The impact of nonsteroidal anti-inflammatory drug-induced gastropathy.
AB  - Gastric and duodenal injury related to nonsteroidal anti-inflammatory drug
      (NSAID) use is extremely common, and a variety of strategies can be employed to
      reduce this frequent side effect of an otherwise useful category of medications.
      Although the best approach may be to discontinue NSAID treatment, this is not
      always possible for patients with arthritis pain or for those who require low
      dose aspirin therapy for underlying cardiovascular disease. In arthritis cases,
      one of the new cyclooxygenase-2 specific inhibitors can be used to replace a
      traditional NSAID, but the addition of another drug to treat and heal ulcers is
      normally still needed. Patients taking aspirin are also candidates for additional
      treatment.

PMID- 11225349
TI  - How far to go? Screening and surveillance in Barrett's esophagus.
AB  - There is no dispute that Barrett's esophagus (BE) is associated with an increased
      risk of esophageal adenocarcinoma. Detecting these cancers early can improve
      patient survival. But should screening be used to detect BE, or should a
      surveillance program monitor those already diagnosed with BE for neoplastic
      changes? Endoscopy and endoscopic biopsy are the only tools available for such
      screening and surveillance, and the cost effectiveness of either approach must be
      considered. Two possible solutions are discussed. First, screening could be
      limited to patients considered at high risk for BE and associated adenocarcinoma.
      With this approach, more precise risk stratification would be required. The
      second possible approach is to combine screening for high-risk patients and
      surveillance for those already diagnosed with BE. Additional outcomes data are
      needed to determine how often and for what length of time endoscopic surveillance
      should continue in a patient after several examinations are negative for
      adenocarcinoma.

PMID- 11225350
TI  - Debating the role of Helicobacter pylori infection.
AB  - Discussion continues on the role of Helicobacter pylori. The following debate
      provides a venue to examine 2 sides of this complicated issue. Dr. Vakil presents
      evidence that the eradication of H pylori will improve patients' health, while
      Dr. Go introduces evidence that suggests the presence of H pylori can be
      beneficial in particular cases. These clinicians also discuss the issue of
      whether to test and treat for H pylori and the role of H pylori in patients with
      gastroesophageal reflux disease.

PMID- 11225351
TI  - Beyond heartburn: extraesophageal manifestations of gastroesophageal reflux
      disease.
AB  - A variety of extraesophageal presentations of chronic acid reflux disease may be
      encountered in practice, and it is important to diagnose and manage them
      appropriately. Some of these patients are asymptomatic; others have symptoms most
      commonly associated with a pulmonary or otolaryngologic disorder. An aggressive
      trial of antireflux medication can often improve or resolve these symptoms,
      indicating that gastroesophageal reflux disease is the primary contributing
      component. In cases where such medication trials fail, additional diagnostic
      methods may be needed to determine the source of the symptoms.

PMID- 11225352
TI  - Characterizing speciation of trace elements in the chemistry of life.

PMID- 11225353
TI  - Quantification of derivatives of bisphenol A diglycidyl ether (BADGE) and novolac
      glycidyl ether (NOGE) migrated from can coatings into tuna by HPLC/fluorescence
      and MS detection.
AB  - A reversed phase high performance liquid chromatographic method combined with
      fluorescence and mass spectrometric detection in series is presented for the
      separation and quantification of bisphenol A diglycidyl ether (BADGE) and novolac
      glycidyl ether (NOGE) derivatives in extracts from food can coatings, tuna and
      oil. Fifteen samples of tuna cans bought in four European countries were
      investigated. Atmospheric pressure chemical ionization mass spectrometry in the
      positive ion mode (APCI(+)-MS) allowed to tentatively identify BADGE and NOGE
      related compounds originating from reactions of the glycidyl ethers with
      bisphenols, phenol, butanol, water and hydrochloric acid. Quantification was
      based on the external standard method and fluorescence detection. Mass fractions
      up to 3.7 micrograms/g were found for hydrochlorination products of bisphenol F
      diglycidyl ether (BFDGE + 2HCl) in tuna. Furthermore, total migration quantities
      of phenolic ether compounds were estimated. The highest values found were 20
      micrograms/g in tuna and 43 micrograms/g in the oil phase.

PMID- 11225354
TI  - Quantitative resolution of spectroscopic systems using computer-assisted target
      factor analysis (CAT).
AB  - Factor analysis (FA) is widely applicable in analytical chemistry. For suitable
      data structures, the generality of the approach is a strong point of FA. Using
      target testing procedures, a wealth of specific informations on the components in
      a chemical system can be extracted without stating a specific model. Target
      testing, however, is time-consuming and often heuristic. In the following,
      application of a computer-assisted target factor analysis (CAT) algorithm is
      described. CAT estimates a rotation matrix that transforms abstract factors into
      physically meaningful informations by using general constraints, i.e. non
      negativity of absorptions and/or concentrations. Thus, the rotation step in
      factor analysis is automated and allows application of target factor analysis to
      situations where none or only very limited information on the real factors and
      their respective contributions is available. Thus, a target testing procedure of
      guessing physically meaningful factors and iteratively adapting these factors is
      performed automatically. Nevertheless, CAT is not a black box procedure. The
      relative importance of different optimization constraints is balanced
      interactively. CAT can be applied to all situations where factor analysis can be
      used. CAT is demonstrated using UV-Vis absorption spectra of a Nd(III)
      polyoxometalate cryptate system and the system U(VI)-CO2-H2O as examples.

PMID- 11225355
TI  - Application of plasma gas modulation technique for improvement of the measurement
      of Mn emission intensity in ICP-AES.
AB  - A phase-sensitive detection technique associated with a digital lock-in amplifier
      was applied for an improvement of the detection in ICP-AES. The lock-in amplifier
      works as an extremely narrow band pass filter. It can pick up the modulated
      signal, which has the same frequency as the reference signal, from any noise and
      thus it can improve the signal-to-noise ratio. Modulation of the ICP can be
      performed by mixing small amounts of air to argon as the outer gas cyclically,
      because the emission intensities of ionic lines are enhanced by using the mixed
      gas. An electromagnetic valve, which is placed in the outer-gas flow path, causes
      periodic variation in the air gas in the outer-gas flow, and thus switching the
      valve on/off can modulate the ICP. By choosing the appropriate conditions, the
      addition of air gas enhances the emission intensity of ionic lines more than that
      of the background, thus leading to improved signal-to-background ratios. At the
      same time the lock-in amplifier further enhances the ionic emissions because it
      picks up only the modulated part of the signal. By applying the plasma gas flow
      modulation technique the detection and the determination limits of the Mn II
      257.610 nm line are improved in comparison with the conventional method. A change
      in plasma shape corresponding to the modulation frequency is observed when the
      ICP is modulated.

PMID- 11225356
TI  - Single-use optical sensor for the determination of iron in water and white wines.
AB  - A new method, based on the use of a disposable sensor, for the determination of
      Fe(II) in waters and wines is proposed. The sensor is formed by an inert
      rectangular strip of polyester (Mylar) and a circular film (6 mm in diameter)
      adhered on its surface. This film, which contains the required reagents for the
      fixation of the analyte by means of a complexation reaction, forms the sensing
      zone of the sensor. When the sensor is introduced in an acidified (pH 2.5) sample
      solution containing between 4.0 and 300.0 micrograms/L of Fe(II), a violet-red
      colour develops in the initially colourless sensing zone. The linear range of the
      method depends on the equilibration time of the sensor with the sample solution.
      Thus, when the equilibration time was 5 min, the linear range was 41.0-300.0
      micrograms/L, while for 60 min the range was 4.0-50.0 micrograms/L. Detection and
      quantification limits were 12.0 and 41.0 micrograms/L, respectively, for an
      equilibration time of 5 min. The precision of the method, expressed as relative
      standard deviation of ten samples of 100.0 micrograms/L of Fe(II), was 4.9%.
      Interferences produced by other species usually present in waters or wines have
      been studied. Cu(II) and Co(II) interfered seriously at concentration levels
      higher than 100.0 and 150.0 micrograms/L, respectively. The method was applied to
      the determination of Fe(II) in different types of waters and wines, using atomic
      absorption spectrometry as a reference method.

PMID- 11225357
TI  - Quinoprotein glucose dehydrogenase modified thick-film electrodes for the
      amperometric detection of phenolic compounds in flow injection analysis.
AB  - The use of thick-film electrodes as basic transducers for highly sensitive
      amperometric biosensors using PQQ (pyrroloquinoline quinone) dependent glucose
      dehydrogenase (GDH) with short response times is described. The enzyme is
      embedded in a polyurethane matrix on top of a platinum based thick film electrode
      and its ability to reduce oxidized phenolic compounds is exploited. The
      electrochemical amplification is based on the oxidation of the analyte on the
      surface of the electrode followed by its enzymatic reduction. Different
      parameters of the glucose dehydrogenase electrode system using dopamine as a
      model analyte were optimized, e.g., membrane thickness, pH value, buffer system,
      flow rate and storage conditions. Using optimized parameters the sensitivity and
      detection limits for various phenolic compounds were evaluated. The comparison of
      electrodes from the identical as well as from different batches shows the ability
      to produce a number of well reproducible sensors showing remarkably small
      differences with respect to parameters as sensitivity, response times and
      measuring range.

PMID- 11225358
TI  - Surface-renewable cobalt(II) hexacyanoferrate-modified graphite organosilicate
      electrode and its electrocatalytic oxidation of thiosulfate.
AB  - Cobalt(II) hexacyanoferrate (CoHCF) was deposited on graphite powder by an in
      situ chemical deposition procedure and then dispersed into methyltrimethoxysilane
      derived gels to prepare a surface-renewable CoHCF-modified electrode. The
      electrochemical behavior of the modified electrode in different supporting
      electrolyte solutions was characterized by cyclic voltammetry. In addition,
      square-wave voltammetry was employed to investigate the pNa-dependent
      electrochemical behavior of the electrode. The CoHCF-modified electrode showed a
      high electrocatalytic activity toward thiosulfate oxidation and could thus be
      used as an amperometric thiosulfate sensor.

PMID- 11225359
TI  - Discussion of parameters associated with the determination of arsenic by
      electrothermal atomic absorption spectrometry in slurried environmental samples.
AB  - A slurry sampling-fast program procedure has been developed for the determination
      of arsenic in plants, soils and sediments by electrothermal atomic absorption
      spectrometry. Efficiencies of various single and mixed modifiers for thermal
      stabilization of arsenic and for a better removal of the matrix during pyrolysis
      step were compared. The influence of the slurry concentration, amounts of
      modifier and parameters of the pyrolysis step on the As integrated absorbance
      signals have been studied and a comparison between fast and conventional furnace
      programs was also made. The ultrasonic agitation of the slurry followed by a fast
      electrothermal program using an Ir/Mg modifier provides the most consistent
      performance in terms of precision and accuracy. The reliability of the whole
      procedure has been compared with results obtained after application of a wet
      digestion method with an HF step and validated by analyzing eleven certified
      reference materials. Arsenic detection and quantitation limits expressed on dry
      sample matter were about 30 and 100 micrograms kg-1, respectively.

PMID- 11225360
TI  - Direct ultrasonic agitation for rapid extraction of organic matter from airborne
      particulate.
AB  - Direct ultrasonic extraction (DUE) is proposed as simple and rapid sample
      pretreatment method. This new approach is applied to the extraction of
      particulate organic matter (POM) from airborne particulate by using
      dichloromethane (DCM) or DCM/methanol (90/10, v/v) as extractant. The analytical
      determination was carried out by weighing the extractable POM on an
      electrobalance. Total recovery for POM could be obtained when the sample was
      extracted three times with 25-50 mL extractant each for about 5 min at 50 W
      ultrasonic power. In comparison with conventional Soxhlet extraction, less
      extraction time (total 15 min only) and solvent consumption (100 mL) were
      required by DUE. The efficiency of the DUE was similar or even higher than the
      routine Soxhlet method. Additionally, the new extractor is very simple and easy
      to use and can accelerate the extraction procedures of organic components from
      various solid samples.

PMID- 11225361
TI  - Determination of lead in fine particulates by slurry sampling electrothermal
      atomic absorption spectrometry.
AB  - A simple method for determining lead in fine particulates (PM2.5) by using
      electrothermal atomic absorption spectrometry (ETAAS) has been developed.
      Particulates collected on Nuclepore filter by using a dichotomous sampler were
      suspended in diluted nitric acid after ultrasonic agitation. The dislodging
      efficiency is nearly 100% after agitation for 5 min. In order to study the
      suspension behavior of PM2.5 in solvents, a Brookhaven ZetaPlus Particle Size
      Analyzer was used to determine the particle size distribution and suspension
      behavior of air particulates in the solvent. The pre-digestion and modification
      effect of nitric acid would be discussed. Palladium was added as a chemical
      modifier and the temperature program of ETAAS was changed in order to improve the
      recovery. The slurry was introduced directly into a graphite tube for
      atomization. The metal content in the sample was determined by the standard
      addition method. In addition, a conventional acid digestion procedure was applied
      to verify the efficiency of the slurry sampling method. It offers a quick and
      efficient alternative method for heavy metal characterization in fine
      particulates.

PMID- 11225363
TI  - Dissolution of molybdenum-silicon (-boron) alloys using a mixture of sulfuric,
      nitric and hydrofluoric acids and a sequential correction method for ICP-AES
      analysis.
AB  - For the major component analysis of Mo-Si (-B) alloys by ICP-AES, an appropriate
      dissolution method is necessary. The general procedure using a HNO3-HF mixture
      cannot be applied for Mo-Si (-B) alloys due to Si volatilization followed by
      violent reaction and due to MoO2 precipitation in the preparation of a Mo
      standard solution from metallic Mo. Good results were obtained with a mixture of
      10 mL H2SO4, 1 mL HNO3, 2 mL HF and 12 mL H2O for Mo-Si (-B) alloys. The samples
      were completely dissolved at room temperature without any losses. A sequential
      correction method is also suggested to correct several errors in ICP-AES analysis
      such as fluctuation in the emission intensities, spectral interferences, non
      spectral interferences and blank values.

PMID- 11225362
TI  - Determination of the pesticide naptalam and its degradation products by positive
      and negative ion mass spectrometry.
AB  - N-1-Naphthylphtalamic acid (naptalam) and its degradation products, 1
      naphthylamine and N-(1-naphthyl) phthalimide were simultaneously determined in
      river water by two independent mass spectrometric (MS) methods. These were
      negative ion MS (NIMS) and programmable temperature vaporizer gas chromatography
      mass spectrometry (PTV-GC MS) with electron impact ionization (positive ions).
      Prior to the NIMS analysis, the samples were preconcentrated by solid phase
      extraction (SPE) of C18 membrane discs. The PTV-GC MS studies were performed
      without any preconcentration procedure. Selected ion monitoring (SIM) and
      internal standardization with naphthalene were applied in both methods. The
      limits of determination (LOD) of NIMS studies were 230, 270 and 260 ng L-1 for
      naptalam, 1-naphthylamine and N-(1-naphthyl) phthalimide, respectively, with
      relative standard deviation (RSD) < 1% (n = 5) and of PTV-GC MS 17, 11 and 15 ng
      L-1 (RSD < 0.7%, n = 5). The LOD, linearity, RSD and time required for these
      methods are far better than for HPLC analyses.

PMID- 11225364
TI  - Molybdenum determination in iron matrices by ICP-AES after separation and
      preconcentration using polyurethane foam.
AB  - A procedure is proposed for the separation and determination of molybdenum in
      iron matrices by a batch process. It is based on the solid-phase extraction of
      the molybdenum(V) ion as thiocyanate complex on polyurethane (PU) foam. The
      extraction parameters were optimized. Using 0.20 mol L-1 hydrochloric acid, a
      thiocyanate concentration of 0.10 mol L-1, 100 mg of polyurethane foam and
      shaking time of 10 min, molybdenum (5-400 micrograms) can be separated and
      preconcentrated from large amounts of iron (10 mg). Desorption was carried out
      instantaneously by conc. nitric acid or acetone. Distribution coefficients,
      sorption capacity of the PU foam and coefficients of variation were also
      evaluated. The effect of some ions on the separation procedure was assessed.
      Iron(III) should be reduced to iron(II). The proposed procedure was used to
      determine molybdenum in standard iron matrices such as steel and pure iron. The
      achieved results did not show significant differences with certified values.

PMID- 11225365
TI  - Separation of gallium and indium from ores matrix by sorption on Amberlite XAD-2
      coated with PAN.
AB  - A chelating sorbent obtained by adsorption of 1-(2-pyridylazo)-2-naphthol (PAN)
      on Amberlite XAD-2 was used for the preconcentration of Ga and In. The analytical
      characteristics of the chelating sorbent were investigated and optimun sorption
      conditions for these metals under dynamic conditions were established. A
      peristaltic pump is used to adjust the flow rate of the solution. Elements are
      collected from the column by using a mixture adjusted to a pH range of 4-7 and 6
      12 by ammonia or ammonium chloride for Ga and In, respectively. The procedure
      developed was applied to the analysis of different ores.

PMID- 11225366
TI  - Separation of vanadium, niobium and tantalum as ternary mixed-ligand complexes by
      capillary electrophoresis using chelation with 4-(2-pyridylazo)resorcinol and
      tartaric acid.
AB  - Vanadium(V), niobium(V) and tantalum(V) were separated as ternary mixed-ligand
      complexes by capillary electrophoresis using 4-(2-pyridylazo)resorcinol (PAR) as
      the color chelating reagent. Four carboxylic acids such as tartaric acid (Tart),
      oxalic acid, citric acid and acetic acid were investigated as the additional
      ligand. The first was chosen as the best. Other parameters such as the
      concentration ratio of Tart to PAR, buffer concentration, injection time and
      applied voltage were also optimized. Under the optimized conditions, a complete
      separation of the three metal complexes was accomplished within 10 min. A linear
      calibration curve in the range of two orders of magnitude was obtained.

PMID- 11225367
TI  - Conversion factor. New law mandates quick switch to safety products.

PMID- 11225368
TI  - Rare breed. St. Louis system goes the extra mile in seeking Baldrige Award.

PMID- 11225369
TI  - Benchmarks 2001.

PMID- 11225370
TI  - Peek under the hood and other tips for buying used equipment.

PMID- 11225371
TI  - FAQs on ASPs. What application service providers can do for you.

PMID- 11225372
TI  - In pursuit of service excellence.

PMID- 11225373
TI  - Pennsylvania court decision on physician's rights raises questions. Carlini v.
      Highmark.

PMID- 11225374
TI  - Court permits home health provider to withdraw. Couch v. Visiting Home Care
      Service.

PMID- 11225375
TI  - Health plan denied possession of former provider's patients' medical records.
      Humana Medical Plan, Inc. v. Fischman.

PMID- 11225376
TI  - Management of acute exacerbations of chronic obstructive pulmonary disease.

PMID- 11225377
TI  - Public health implications of dengue in personnel returning from East Timor.
AB  - In north Queensland the vector of dengue fever (Aedes aegypti) is present; hence
      any viraemic individual importing dengue has the potential to transmit the
      disease locally. In early 2000 approximately 2,000 personnel returned from East
      Timor to Townsville, north Queensland. Seven importations of dengue occurred and
      individual cases were viraemic for up to 6 days in Townsville. No subsequent
      local transmission occurred. There were 3 cases each of dengue type 2 and dengue
      type 3. One case could not be serotyped. A response, including mosquito control
      measures, was initiated in another 18 cases in which dengue fever was clinically
      suspected but which subsequently proved not to be dengue. The planning and
      processes undertaken to prevent local transmission of dengue in Townsville during
      an intense period are described.

PMID- 11225378
TI  - Murray Valley encephalitis in Western Australia in 2000, with evidence of
      southerly spread.
AB  - We describe the epidemiological and clinical features of human Murray Valley
      encephalitis (MVE) and Kunjin (KUN) virus infections in Western Australia (WA)
      during March to July 2000. A case series was performed. For laboratory-confirmed
      cases, travel histories and clinical details were collected from patients, family
      members, friends or treating physicians. Surveillance data from the sentinel
      chicken program and climatic conditions were reviewed. Nine encephalitic cases of
      MVE were recorded. Eight were non-Aboriginal adults (age range, 25 to 79 years; 5
      male, 3 female) and 1 was an Aboriginal boy. Four cases acquired infection in the
      Murchison and Midwest regions of WA from which no human cases of MVE have been
      reported previously. One of the 9 cases was fatal and 3 had severe neurological
      sequelae. Five non-encephalitic infections were also recorded, 3 MVE and 2 KUN.
      Encephalitis caused by MVE virus remains a serious problem with no improvement in
      clinical outcomes in the last 25 years. Excessive rainfall with widespread
      flooding in the northern two-thirds of WA provided ideal conditions for mosquito
      breeding and favoured southerly spread of the virus into new and more heavily
      populated areas. Surveillance in WA with sentinel chickens and mosquito trapping
      needs expansion to define the boundaries of MVE virus activity. To enable timely
      warnings to the public, and to institute mosquito control where feasible,
      continued surveillance in all Australian areas at risk is indicated.

PMID- 11225379
TI  - Notifiable disease reporting in the new millennium.

PMID- 11225380
TI  - The outbreak that had to happen: Bordetella pertussis in north-west Western
      Australia in 1999.
AB  - In late 1999, an outbreak of Bordetella pertussis occurred in a small town in
      North-West Western Australia. We undertook an investigation to describe the
      outbreak and to identify strategies to minimise the impact of future pertussis
      outbreaks in Australia. In November, people with respiratory symptoms were
      reviewed in an emergency pertussis clinic, which provided antibiotic treatment or
      prophylaxis. We conducted a school survey to enhance case ascertainment and
      followed up those attending the clinic by telephone. Fifty-nine cases of
      confirmed or probable B. pertussis infection were identified from 124 households
      (482 persons). Ages ranged from 5 months to 67 years, with children aged 9 to 11
      years comprising 24 cases (41%). Early missed diagnoses and a school camp in
      September attended by 2 symptomatic children appeared to facilitate spread of
      infection, with the outbreak peak occurring in November. From immunisation
      records, childhood vaccine coverage in this sample was estimated at 96 per cent.
      All 21 cases of pertussis among the group under 10 years of age were at least
      partially vaccinated. There was only one laboratory confirmed case in the high
      risk, under one-year of age category. Even in highly immunised populations
      periodic pertussis outbreaks are inevitable reflecting a vaccine efficacy of
      about 80 per cent and waning immunity with increasing age. Prevention of
      pertussis outbreaks depends not only on high vaccination coverage among young
      children but also early diagnosis and management of cases and their contacts.
      Clinicians should consider pertussis in the differential diagnosis of persistent
      cough illness in people of all ages--even those previously immunised.

PMID- 11225381
TI  - Laboratory-supported influenza surveillance in Victorian sentinel general
      practices.
AB  - Laboratory-supported influenza surveillance is important as part of pandemic
      preparedness, for identifying and isolating candidate vaccine strains, for
      supporting trials of anti-influenza drugs and for refining the influenza
      surveillance case definition in practice. This study describes the implementation
      of laboratory-supported influenza surveillance in Victorian sentinel general
      practices and provides an estimate of the proportion of patients with an
      influenza-like illness proven to have influenza. During 1998 and 1999, 25
      sentinel general practices contributed clinical surveillance data and 16
      metropolitan practices participated in laboratory surveillance. Serological,
      virus-antigen detection, virus culture and multiplex polymerase chain reaction
      procedures were used to establish the diagnosis of influenza. Two laboratories at
      major teaching hospitals in Melbourne provided additional data on influenza virus
      identification. General practice sentinel surveillance and laboratory
      identification of influenza provided similar data on the pattern of influenza in
      the community between May and September. The clinical suspicion of influenza was
      confirmed in 49 to 54 per cent of cases seen in general practice.

PMID- 11225382
TI  - A decision to end a periodic syphilis-screening program in the Kimberley region.
AB  - Syphilis rates in the Kimberley region of far-northern Western Australia are
      among the highest in the nation. In 1986, a formal program of periodic syphilis
      screening was established. Decreasing syphilis rates since the early 1990s
      prompted, in 1999, re-evaluation of the value of periodic screening. All
      confirmed cases of syphilis identified in the Kimberley between January 1996 and
      early December 1999 as a result of syphilis serology were classified by reason
      for the test and staged according to disease progression. During the study
      period, 196 cases of syphilis (117 male, 79 female) were diagnosed; 14 (7.1%)
      were primary, 32 (16.3%) secondary and 150 (76.5%) latent. The periodic screening
      program contributed only about 10 per cent of cases, whereas testing as a result
      of sexually transmitted disease symptoms, sexually transmitted disease contact,
      institutional screening and other screening contributed the remaining cases. In
      January 2000, the periodic syphilis-screening program was discontinued. The
      effect of this policy change will be closely monitored using indicators to ensure
      that, should the decision not to screen prove to have been misjudged, any
      increase in syphilis incidence is detected early and managed appropriately.

PMID- 11225383
TI  - Communicable diseases surveillance.

PMID- 11225384
TI  - [Schonlein-Henoch purpura associated with hepatitis B in a patient with HIV
      infection].
AB  - HISTORY AND CLINICAL FINDINGS: A 23-year-old man with HIV-infection and recently
      diagnosed hepatitis B infection developed painful swelling and palpable purpura
      in the limbs. In addition, relapsing diarrhoea, arthralgia and pain at the level
      of the right kidney were noted. The liver, the palpable lymph nodes and the
      tonsils were enlarged. INVESTIGATIONS: The following laboratory parameters were
      abnormal: sedimentation rate 64/70 mmHg, CD4+ cells 462/ml, CD4/CD8 ratio 0.3,
      serum CRP 16 mg/l, antistreptolysin titre 542 kU/l, complement C3 < 0.1 g/l, GPT
      37 U/l, albumin 49.5% and gamma-globulin 28.5%, in urine, leukocytes
      25/microliter and protein 0.25 g/l. Hepatitis serology: anti-HBc, HBs-Ag and HBe
      Ag positive, anti-HBs and anti-HBe negative, hepatitis A-Ab (IgG) positive,
      hepatitis A-Ab (IgM) negative, hepatitis C-Ab negative. Pharyngial swab: beta
      haemolytic streptococci of group A. Stool examination: amoeba cysts, corona virus
      and fungi 10(4)-10(5)/ml (control specimen negative). Abdominal sonography showed
      minor hepatomegaly, splenomegaly and two 0.8 cm-large lymph nodes near the liver
      entrance. The histology of a skin lesion revealed a florid leukocytoclastic
      vasculitis at the upper and middle dermal vessels. The immunohistological
      examination detected IgA, IgM and C3 deposits. TREATMENT AND COURSE: The multiple
      bacterial infections had initially been considered as triggering the Schonlein
      Henoch purpura. However despite successful treatment of these infections severe
      relapses of both the skin lesions and the systemic manifestations occurred. A
      drug reaction, autoimmune diseases and tumours were excluded. Only after
      treatment of hepatitis B infection with recombinant interferon alpha together
      with administration of zidovudine (treatment of choice at that time) the lesions
      quickly disappeared without further relapses. During the 5-year-follow-up,
      recurrent bacterial infections did not induce relapses of the disease, whereas
      the hepatitis B infection was seroconverted. CONCLUSION: It is likely that the
      hepatitis B may have been the trigger for the Schonlein-Hennoch-purpura.

PMID- 11225385
TI  - [Hemosuccus pancreaticus (bleeding into the pancreatic duct). A rare complication
      of pancreatitis].
AB  - HISTORY AND ADMISSION FINDINGS: A 41-year-old man was admitted because of
      recurrent tarry stools and dizziness. Chronic pancreatitis induced by alcoholism
      was known. The main abnormal laboratory finding was anaemia (haemoglobin 4.6
      g/dl, erythrocytes 2.28/fl). INVESTIGATIONS, TREATMENT AND COURSE: At endoscopy
      of the oesophagus, stomach and duodenum, fresh blood was found in the duodenum, a
      small trickle of blood coming from the papilla of Vater. Endoscopic retrograde
      cholangiography discovered no abnormality in the biliary system. Selective
      contrast imaging of the pancreatic duct demonstrated a short prepapillary
      stenosis and a prestenotic dilatation (up to 15 mm diameter) of the pancreatic
      duct with a cloudy contrast filling defect. After catheter withdrawal from the
      pancreatic duct blood spurted from the papilla. Emergency angiography revealed
      pseudoaneurysmatic dilatation of the gastroduodenal artery in the region of the
      head of the pancreas. At selective catheterization this artery was successfully
      occluded with metal coils placed both proximally and distally to the source of
      bleeding. CONCLUSION: Gastrointestinal bleeding is a rare but potentially life
      threatening complication of pancreatitis. When searching for bleeding in the
      upper gastrointestinal tract, the papilla of Vater should be looked for as a
      possible source. Bleeding from the pancreas occurs particularly in pancreatitis,
      pancreatic pseudocyst or pancreatic tumour.

PMID- 11225386
TI  - [Diagnosis and staging of pancreatic carcinomas].

PMID- 11225387
TI  - [Liver diseases caused by alcohol consumption and hepatitis C virus infection:
      association, addition or potentiation?].

PMID- 11225388
TI  - [Report of the original Medical Foundation for Patient Justice. Decision of
      County Court of Munich from 11.15.2000].

PMID- 11225390
TI  - [Multilocational thyroid ectopic tissue].

PMID- 11225389
TI  - [Premedication for endoscopy].

PMID- 11225391
TI  - [Cardiomyopathy in obesity--a clinical entity].

PMID- 11225392
TI  - [Cardiomyopathy in obesity--a clinical entity].

PMID- 11225393
TI  - [Retrospective cohort study of lamivudine therapy in patients with chronic
      hepatitis B].
AB  - BACKGROUND AND AIMS: Lamivudine, a nucleoside analogue with specific antiviral
      activity against the hepatitis B virus, is now available as an alternative
      therapeutic option to standard interferon-alpha treatment in chronic hepatitis B.
      Larger studies with lamivudine treatment in chronic hepatitis B were mainly
      performed in North America and Asia. Data on treatment responses in European
      patients are sparse. Therefore, we evaluated the efficacy and safety of
      lamivudine therapy in Central European patients and compared the data with the
      results from international trials. PATIENTS AND METHODS: In this retrospective,
      multicenter, cohort study, 95 patients with chronic hepatitis B (median age: 40.4
      years, male: 87 patients, female: 8 patients, HBeAg positive: 47 patients, anti
      HBe positive: 48 patients), who were treated with lamivudine (100-300 mg/d per
      os) between 1997 to 1999, were enrolled. RESULTS: During lamivudine treatment a
      virologic response with HBeAg to anti-HBe seroconversion was achieved in 22/47
      (47%) of the HBeAg positive patients. Pretreatment ALT levels (> threefold the
      upper limit of normal; p = 0.03) and HBV-DNA serum concentration (< or = 100
      pg/ml; p = 0.08) were identified as positive predictors for virologic responses.
      The virologic response was sustained in six of nine patients who had a follow-up
      period (median 26 weeks). In anti-HBe positive patients a virologic response with
      undectable HBV-DNA levels was achieved in 35/48 (73%) patients during lamivudine
      treatment. Side effects during lamivudine therapy were generally mild and
      reversible. CONCLUSIONS: In this retrospective cohort study virologic end-of
      treatment responses to lamivudine monotherapy in patients with chronic hepatitis
      B were comparable with yet reported international trials. Thus, lamivudine
      represents a cost-effective and well tolerable option in addition to IFN-alpha in
      the treatment of chronic hepatitis B.

PMID- 11225394
TI  - [Evaluation of extensive visual field defects with computer-assisted kinetic
      perimetry].
AB  - BACKGROUND: Conventional kinetic perimetry is of especial use in case of advanced
      scotoma. However, examiner dependency is a major drawback. Purpose of this study
      was to evaluate the clinical feasibility and intraindividual scatter of computer
      assisted kinetic perimetry in monitoring advanced visual field defects of various
      origins. METHODS: Examinations were carried out with the Tuebingen Computer
      Campimeter (background lumincance 10 cd/m2). In an initial session, the
      localization of the scotoma border is estimated with conventional manual kinetic
      perimetry. In the subsequent computer assisted kinetic mode, an individually
      adjusted set of vectors is designed. Each vector crosses the manually assessed
      visual field defect border almost perpendicularly, starting approximately 3
      degrees within the scotoma. Each individual set of vectors can be stored and
      recalled for follow-up. Stimuli move along these vectors with identical
      characteristics as in manual kinetic perimetry. Stimulus presentations are
      repeated six times in a randomized order. Patients' responses are recorded and
      additionally corrected for mean individual reaction time. A "local kinetic
      threshold" (mean) and a related parameter for dispersion (standard deviation) are
      assessed. RESULTS: Four subjects with advanced visual field loss of various
      origin (retinitis pigmentosa, vigabatrin-associated visual field defect,
      glaucomatous nerve fibre layer defect, and postgeniculate visual pathway defect)
      participated in this study. Maximal difference between manual-kinetic and
      automated kinetic thresholds reaches from 1.7 degrees to 5 degrees. Local scatter
      (standard deviation) of kinetic threshold, assessed by computer-assisted
      perimetry, varies between 0.1 degree and 3.0 degrees. CONCLUSION: Computer
      assisted kinetic perimetry is a new, useful, examiner-independent, reliable
      method for effective evaluation and monitoring of advanced visual field loss.

PMID- 11225395
TI  - [Automated swinging flashlight test in patients with optic nerve diseases].
AB  - AIM OF THE STUDY: The swinging flashlight test is an objective method to diagnose
      a lesion of the anterior visual pathways. However, errors and faults may easily
      alter the test's results. Hence, the value of the swinging flashlight test
      depends highly on the examiner's skills. Therefore an automated and objective
      procedure was developed which is independent from the examiner. METHODS: A
      binocularly measuring instrument adapted for video pupillography was supplied
      with two arrays of light emitting diodes in front of each eye of the subject. By
      means of this illumination, pupillary light reflexes are elicited alternately.
      Pupil size is registered continuously, and after artifact elimination, the
      response amplitudes of the pupils are determined as a mean of right and left
      pupil. Responses elicited via right and left eye are compared. By varying the
      stimulus intensity it is possible to measure the amount of the relative afferent
      pupillary defect. The procedure was tested in 31 patients with optic nerve
      disorders. RESULTS: The measurements were easily feasible, stable and reliable.
      Correlation between the relative afferent pupillary defect detected manually by
      grey filter compensating and with the automated procedure proved to be high. Both
      variables correlated highly significant with a Spearman rank coefficient of 0.65.
      If the clinical test is regarded as the golden standard, the automated swinging
      flashlight test is able to detect 85% of the relative afferent pupillary defects
      > or = 0.3 logE and 94% of the defects > or = 0.6 logE. CONCLUSION: The automated
      swinging flashlight test can be recommended to exclude influences by the examiner
      or if the exact amount of the relative afferent pupillary defect is desired, e.g.
      when monitoring therapeutic effects in optic nerve diseases. Furthermore, an
      automated swinging flashlight test could serve as a screening test.

PMID- 11225397
TI  - [Analysis of 180 patients with sensory defect nystagmus (SDN) and congenital
      idiopathic nystagmus (CIN)].
AB  - AIM: Analysis of the diseases underlying congenital nystagmus in a series of
      patients registered during 6 years as a prerequisite for adequate counselling of
      the families. PATIENTS AND METHODS: Retrospective study of all patients that
      presented between 1992 and 1998 with congenital nystagmus not related to visual
      deprivation or acquired pathologies of the visual pathways. The patients were
      examined clinically and in dependence on the findings also by
      electrophysiological (Ganzfeld ERG and VEP, Albino-flash-VEP), psychophysical
      (colour vision, dark adaptation, spectral sensitivity), and molecular genetic
      methods. When estimated necessary, family members affected by history and
      unaffected family members were also examined. In cases of complex
      neuroophthalmological diseases a neuropaediatric examination including
      neuroimaging was initiated. RESULTS: In total, 180 patients could be analysed. A
      sensory defect nystagmus (SDN) was present in 142 patients (79%). The diagnoses
      were as follows: albinism (any form) in 56 patients (30%), progressive
      photoreceptor dystrophy in 20 patients (11%), stationary cone dysfunction in 18
      patients (10%), bilateral optic nerve hypoplasia in 15 patients (8%),
      chorioretinal or optic nerve colobomata in 10 patients (6%), aniridia and its
      variants in 10 patients (6%), familial isolated nystagmus in 8 patients (5%), and
      congenital stationary night blindness in 5 patients (3%). 38 patients (21%) could
      not (yet) be classified. DISCUSSION: The prevalence of SDN as the manifesting
      symptom of a variety of well defined diseases in the present series of at least
      79% is similar to that of 90% reported earlier. The precise diagnosis is a
      prerequisite for counselling the families as to functional prognosis and
      recurrence risk. Unnecessary neurological examinations including neuroimaging can
      be avoided.

PMID- 11225396
TI  - [Experiences with cycloplegic drops in German-speaking centers of pediatric
      ophthalmology and stabology--results of a 1999 survey].
AB  - BACKGROUND: Because of its advantages, topical cyclopentolate is often preferred
      over the gold standard, atropine. The purpose of the study was to obtain an
      overview over current cycloplegia protocols and to estimate the likelihood of
      severe complications due to the use of cycloplegics. METHODS: A questionnaire was
      sent to 107 German-speaking centres with a supposed high cycloplegia frequency.
      RESULTS: 57 centres answered, whereby 1,112 cumulated years of experience with
      cycloplegia were available for analysis. The frequency of cycloplegias varied
      between 2 and 180/week/centre, median 25/week/centre. A cumulated amount of 1.7
      million cycloplegias was computed. The average extrapolated experience with
      cycloplegia was 49,000 cycloplegias/30 years. Severe complications which would
      cause a medical follow up of several hours or which led to a follow up in a ward
      were named 47 times and 2 times, respectively. CONCLUSIONS: During 30 years of a
      cycloplegia career with an average of 34 cycloplegias/week, one may expect 2-10
      severe complications. In current practice, the patient risk of severe
      complications is very small. Health care professionals and parents should be
      informed about the frequent occurrence of light side effects in order to reach a
      good compliance with cycloplegia.

PMID- 11225398
TI  - [Results of combined divergence operation in intermittent exotropia in 120
      children].
AB  - BACKGROUND: Intermittent exotropia is the most frequent indication for surgical
      correction of exodeviations in childhood. Overcorrection with prolongated or
      persistent consecutive esotropia can impair binocular vision particularly in
      early childhood. We wanted to investigate this potential risk and the dose/effect
      relation of recess-resect surgery on children. PATIENTS AND METHODS: 120 children
      up to ten years of age underwent recess-resect surgery for intermittent exotropia
      in our clinic from 1991 to 1999 (< 2% of the surgical cases). The cycloplegic
      refraction was spectacle corrected with a reduction of 0.5 dpt. Preoperatively, a
      diagnostic occlusion was performed for three days. The amount of surgery was
      calculated using our dosage schedules based on effects one week postoperatively.
      The squint angles as measured by the alternate prism and cover test at 5 m and
      0.3 m pre- and 3 months postoperatively and the binocular functions as measured
      by the Bagolini striated glasses, Titmus, Randot, TNO, or Lang tests were
      evaluated. RESULTS: (Medians) Squint angles in primary position were:
      preoperative: distance (5 m)--15 degrees, near (0.3 m)--16 degrees; postoperative
      (n = 104); distance--4 degrees, near--3 degrees. Effectivity of surgery:
      distance: 1.3 degrees/mm, near 1.4 degrees/mm. Consecutive esotropia requiring
      surgical correction occurred in 1 child. Second surgery for intermittent
      exotropia in the years 1991 to 1999 was necessary in 5 children. Binocular
      functions (n = 95): Preoperative = postoperative: 61%, postoperative >
      preoperative 21%, postoperative < preoperative 18%. The diagnostic occlusion was
      helpful to differentiate "pseudo-divergence excess type" from "divergence excess
      type" exotropia. The average deviation did not increase under the diagnostic
      occlusion. The effectivity of surgery (degree/mm) in the children group was lower
      than in a compared group of older patients (> 10 years) with intermittent
      exotropia. CONCLUSION: Using our own dosage schedules and surgical technique,
      residual exodeviations are common after recess-resect surgery in childhood. The
      risk of consecutive esotropia or persistent impairment of binocular vision is
      low.

PMID- 11225399
TI  - [The Titmus Fly Test--evaluation of subjective depth perception with a simple
      finger pointing trial. Clinical study of 73 patients and probands].
AB  - BACKGROUND: Subjects with different binocular defects were tested for their
      stereoscopic achievement. The determination of the subjects limiting disparity
      (in seconds of arc) was not used to characterize their stereoscopic acuity, but
      the subjective depth perception as a simple clinical method. METHODS: 52 subjects
      with different binocular defects and 21 normosensoric volunteers were examined
      for their stereoscopic achievement. In our stereoscopic measurement we ask the
      subjects to indicate the subjective plane of the fly's wings manually by their
      own finger, or by a hand-held plastic card, or with the aid of a mechanic
      instrument. The results of the different methods were compared with each other.
      RESULTS: There were no differences between the results within the group of
      normosensoric subjects. The patients with reduced abilities exhibit significantly
      different results in depth perception when measured manually or by machinery. The
      subjective depth localization correlates well with the binocular defect and is
      independent of the used stereoscopic method. CONCLUSIONS: The basic finger test
      of the subjective level of the Fly's wings gives a quite reasonable approximation
      of local stereoscopic depth perception. In terms of practical investigation the
      finger test shows in convincing manner whether the individual stereoscopic
      ability is based on normal, subnormal or anomalous binocular interaction.

PMID- 11225400
TI  - [Ophthalmoscopic findings in 3 patients with panarteritis nodosa and review of
      the literature].
AB  - BACKGROUND: Ocular involvement in panarteritis nodosa (PAN) has been reported to
      occur in 10 to 20% of patients. In 3 patients with acute visual disturbance we
      point out unusual findings. PATIENTS: Case 1. A 40-year-old man initially
      presented with papilledema together with partial optic atrophy in both eyes,
      later polyneuropathy, gangrene of the toes and myalgic pains developed. Caliber
      changes in the small arteries in the liver were seen angiographically and
      recognized as signs of PAN. Under treatment with cyclophosphamide und prednisone
      no relapse occurred during a follow-up of 2 years. Case 2. In a 67-year-old man
      who suffered from arterial hypertension and coronary heart disease, central
      retinal artery occlusion occurred, at first in the left and then later in the
      right eye. The clinically suspected diagnosis of PAN (arterial hypertension,
      myalgia, polyneuropathy) was confirmed by a muscle biopsy. During a follow-up of
      4 years--including treatment with prednisone and cyclophosphamide--no relapse
      occurred. Case 3. A 16-year-old adolescent with throbbing headaches and a
      thickened right temporal artery reported visual disturbances. These were due to
      an inflammation of choroidal vessels of the right eye appearing as an initial
      sign of PAN. Histology revealed a necrotising arteritis of the temporal artery.
      He presented with signs of Raynaud's disease, cachexia and arterial hypertension.
      Multiple vasculitic changes were detected by aorto-arteriography. Five months
      after the visual deterioration an anterior spinal artery syndrome with
      quadriplegia developed. After a follow-up of 2 years and treatment with
      prednisone und cyclophosphamide, he still had paralysis of both legs. The visual
      acuity was 1.0 in each eye. CONCLUSION: PAN should be considered in differential
      diagnosis in patients with acute inflammatory signs of the optic nerve head, the
      choroid and/or the retina together with general signs of the disease. If the
      disease is suspected, a muscle biopsy is indicated.

PMID- 11225401
TI  - [Optic neuritis as a complication in preventive tetanus-diphtheria-poliomyelitis
      vaccination: a case report].
AB  - BACKGROUND: The preventive value of vaccinations is generally accepted. Public
      recommended vaccinations are administered frequently and therefore even rare
      complications may occur. PATIENT: We report on a 56-year-old patient who suffered
      from an acute unilateral optic neuritis, following ten days after vaccination
      against diphtheria, tetanus and poliomyelitis. A complete remission occurred
      within six weeks after intravenous megadose prednisolone. CONCLUSIONS:
      Neurological and ophthalmological complications following vaccinations are rare,
      and in most cases reversible.

PMID- 11225402
TI  - [Unilateral aplasia of a lateral rectus muscle].
AB  - BACKGROUND: The congenital absence of an extraocular muscle is rare. The case of
      an unilateral lateral rectus muscle and a review of the literature are presented.
      PATIENT AND METHODS: A healthy 7-year old boy with inconspicuous family history
      was seen in our clinic. The boy had been noted to have a right esotropia from
      infancy. Clinical orthoptical examinations and magnetic resonance imaging (MRI)
      were performed. The esotropia was corrected by transposition of the superior and
      inferior rectus muscle. RESULTS: With correction of the myopic astigmatism the
      visual acuity of either eye was 0.8. The right eye could not abduct to pass the
      midline, the left eye passed the midline by 35 degrees. From the primary position
      the right eye was able to elevate by 20 degrees and the left eye to elevate 15
      degrees. The alternate prism and cover test showed in either eye fixation an
      esotropia of 24 degrees without significant change in elevation or depression.
      Besides, there was a hypertropia (+VD) of 14 degrees which increased to 21
      degrees in left gaze and decreased to 0 degree in right gaze. Indirect
      ophthalmoscopy showed a bilateral excyclo position of approximately 5-10 degrees.
      Retraction of either eye was not seen in any gaze direction. The axial length of
      the right/left eye was 25.2 mm/24.6 mm. Aplasia of the right lateral rectus
      muscle and hypoplasia of the left lateral rectus muscle could be demonstrated by
      magnetic resonance imaging. Intraoperatively the right lateral rectus muscle was
      absent. The vertical eye muscle inserted regularly. Hummelsheim's procedure was
      performed. Eight months postoperatively, the boy was orthotropic in primary
      position. The inferior oblique overaction was still present together with a "V"
      pattern of 8 degrees. The Bagolini test was positive. CONCLUSION: The congenital
      absence of one or more extraocular muscles is a rare condition, which has to be
      considered as a differential diagnosis to neurogenic nerve palsy.

PMID- 11225404
TI  - [Contenti estote: refraction--a wallflower in luxuriant garden?].

PMID- 11225405
TI  - [Adjuvant chemotherapy in breast cancer. Open questions and future developments].

PMID- 11225403
TI  - [Localized argyrosis 58 years after strabismus operation--an ophthalmological
      rarity].
AB  - BACKGROUND: A pigmented episcleral lesion may have several etiologies. We
      describe the rare occurrence of a localized argyrosis secondary to former
      strabismus treatment. HISTORY: A 70-year old female patient was referred to our
      clinic for diagnosis and treatment of a pigmented episcleral process near the
      insertion of the left lateral rectus muscle which was noticed on a routine
      control by her ophthalmologist. The patient was free from ocular symptoms. There
      was a history of strabismus surgery on the left eye at the age of twelve. Due to
      the suspicious appearance of the lesion the possibility of a conjunctival
      malignant melanoma was considered. A ultrasound exam could not exclude this
      suspicion and therefore a biopsy was performed. Silver deposits and rests of a
      suture could be found. CONCLUSION: Silver deposits are a rare cause of a
      pigmented localized episcleral lesion. Several possibilities of silver
      contamination in our patient are discussed. The most likely explanation is the
      use of silver containing suture material in strabismus surgery performed 58 years
      ago. A localized argyrosis secondary to past strabismus surgery should therefore
      be included in the differential diagnosis of a pigmented episcleral lesion.

PMID- 11225406
TI  - [New frontieres of treatment in oncology].

PMID- 11225407
TI  - [Oncology in the year 2000: renewal and innovation. Introduction].

PMID- 11225408
TI  - [Adjuvant chemotherapy in breast cancer. International perspective].

PMID- 11225409
TI  - [Adjuvant chemotherapy in breast cancer. New strategies].

PMID- 11225410
TI  - [Management of multiple trauma: Comments on a radiologic "Round the Clock" task].

PMID- 11225411
TI  - [Imaging of breast tumors using MR elastography].
AB  - PURPOSE: Imaging of breast tumors using MR-Elastography. MATERIAL AND METHOD: Low
      frequency mechanical waves are transmitted into breast-tissue by means of an
      oscillator. The local characteristics of the mechanical wave are determined by
      the elastic properties of the tissue. By means of a motion-sensitive spin-echo
      sequence these waves can be displayed within the phase of the MR image.
      Subsequently, these images can be used to reconstruct the local distribution of
      elasticity. In-vivo measurements were performed in 3 female patients with
      malignant tumors of the breast. RESULTS: All patients tolerated the measurement
      set-up without any untoward sensation in the contact area of skin and oszillator.
      The waves completely penetrated the breast, encompassing the axilla and regions
      close to the chest wall. All tumors were localized by MRE as structures of
      markedly stiffer tissue when compared to the surrounding tissue. Furthermore, in
      one patient, a metastasis in an axillary lymph node was detected. In all
      patients, local regions of increased elasticity were found in the remaining
      parenchyma of the breast, which, however, did not reach the high levels of
      elasticity found in the tumors. CONCLUSION: MRE is an imaging modality enabling
      adjunct tissue differentiation of mammary tumors.

PMID- 11225412
TI  - [Quantitative multi-slice imaging of perfusion of the brain].
AB  - AIM: To develop an MR pulse sequence that allows the determination of the
      quantitative perfusion of the brain by imaging the passage of a contrast agent
      bolus with high temporal and spatial resolution. METHODS: An EPI sequence, EPIDET
      (Echo Planar Imaging using Different Echo Times), was developed that allows the
      acquisition of different slices at different echo times. The passage of a
      contrast agent bolus was recorded in a slice through the large brain feeding
      arteries at a short echo time (TE1 = 17 ms), while brain parenchyma was imaged in
      up to nine additional slices at a long echo time (TE2 = 34 ms). RESULTS: The
      different echo times allowed the determination of the arterial input function
      (signal decrease to 32%-59% of baseline intensity) and gave a sufficient signal
      reduction (14-22%) for reliable quantification of perfusion in brain parenchyma.
      CONCLUSIONS: The combination of different echo times of the DUAL-FLASH sequence
      and the multislice capability of EPI sequences in the EPIDET sequence enables the
      quantification of multi-slice perfusion examinations. Compared to the DUAL-FLASH
      sequence EPIDET improves spatial and temporal resolution.

PMID- 11225413
TI  - [Can follow-up controls improve the accuracy of MR mammography? A retrospective
      analysis of MR mammography follow-up studies].
AB  - PURPOSE: To assess the change in diagnostic confidence between first and follow
      up dynamic MR examination of the breast (MRM). METHODS: The reports of a total of
      175 MRM in 77 patients (mean age 50 years; 36-76) with 98 follow-up MRM were
      analyzed. All examinations were performed as a dynamic study (Gd-DTPA, 0.16
      mmol/kg; 6-7 repetitive studies). The change in diagnostic confidence was
      retrospectively classified as follows: controlled lesion vanished during follow
      up (category I); diagnostic confidence increases during follow-up (II), more
      likely benign (IIa), more suspicious (IIb); no difference in diagnostic
      confidence (III). Long-term follow-up over an average of four years was obtained
      for 57 patients with category IIa/III findings. RESULTS: In 98 follow-up
      examinations, only two lesions vanished (2%). In 77/98 cases a category IIa
      lesion was diagnosed, in 11 cases a category IIb lesion. In 8 cases (8%) there
      was no change in diagnostic confidence during follow-up. Lesions in category IIb
      underwent biopsy in 10/11 cases, in one case long-term follow-up proved a
      completely regredient inflammatory change. In 8/11 suspicious findings (IIb) a
      malignant tumor was detected. The mean time interval between first and follow-up
      MRM was 8 months for I-IIb lesions, and 4 months for category III lesions. In the
      long-term follow-up two patients with a category IIa lesion developed a carcinoma
      in a different breast area after four and five years. CONCLUSION: MRM follow up
      increases the diagnostic confidence if the time interval is adequate (> 4
      months). A persistently or increasingly suspicious finding warrants biopsy.

PMID- 11225414
TI  - [MR mammography of response-control in primary chemo-brachytherapy in BCT
      inoperable breast cancer].
AB  - PURPOSE: To evaluate (1) if neoadjuvant chemo-brachytherapy interferes with MR
      imaging, (2) if MR can predict the size of the remaining tumor after therapy and
      (3) if MR can give prognostic information after the onset of therapy.
      MATERIALS/METHODS: 14 patients enrolled in a preoperative tumor-reduction
      protocol (4 cycles of chemotherapy combined with interstitial radiotherapy) were
      examined by dynamic contrast enhanced MR mammography (1 T, temporal resolution 93
      s, spatial resolution 1.9 min, 0.1 mmol/kg GdDTPA), before therapy, after the
      first two cycles of chemotherapy, after radiotherapy and the third cycle, and
      after completion of therapy. MR findings were evaluated for (1) artificial
      enhancement after radiotherapy, (2) correlation of enhancement after therapy with
      histology and (3) changes in enhancement dynamics after the first 2 cycles.
      RESULTS: (1) 54% of patients had diffuse enhancement that occurred after
      radiotherapy but vanished before the end of therapy. (2) 4 patients had complete
      histological remissions after therapy, 3 had dispersed single tumor cells, 7 had
      remaining nodular tumor. While MR could not differentiate between complete
      remission and single tumor cells, it accurately predicted the diameter of
      remaining nodular tumor, except for one case that showed false-positive
      enhancement. (3) MR dynamics after the first cycles of chemotherapy could not
      predict overall response. CONCLUSIONS: MR is an accurate tool in assessing tumor
      response after neoadjuvant chemobrachytherapy. Negative effects from radiotherapy
      are only transient.

PMID- 11225415
TI  - [MR tomographic characterization of suspicious breast lesions with dynamic
      susceptibility-weighted T2* sequences].
AB  - PURPOSE: To increase specificity of MR-mammography by using dynamic T2*
      sequences. METHODS: 23 patients with suspicious lesions of the breast underwent
      conventional dynamic T1-weighted (T1-dynamic) breast MRI and, subsequently,
      dynamic T2*-weighted (T2*-dynamic) perfusion studies. To assess the T1-dynamic,
      signal enhancement during the first minute (E1) was calculated. To evaluate the
      T2*-dynamic, relative signal intensity loss after administration of contrast
      medium was determined. RESULTS: After administration of contrast medium, 6 of 13
      malignant lesions did not show a signal decrease during the T2*-dynamic. Two of
      them exhibited an atypical signal enhancement in the T1-dynamic, with E1 < 100%.
      On the other hand, in 5 of 10 benign tumors a relative signal decrease of between
      5-17% occurred during the T2*-dynamic. Four benign lesions showed a strong early
      signal enhancement during the T1-dynamic (E1 > 100%), which is more typical for
      malignant lesions. DISCUSSION: The use of dynamic T2* sequences, following
      dynamic T1-weighted breast MRI and administration of contrast medium, does not
      sufficiently increase diagnostic sensitivity. Thus, this study does not support
      the potential advantage of susceptibility MR imaging for a further
      characterization of breast lesions.

PMID- 11225416
TI  - [MRI in chronic inflammatory bowel disease].
AB  - Chronic inflammatory bowel disease is diagnosed and monitored by the combination
      of colonoscopy and small bowel enteroklysis. Magnetic resonance imaging has
      become the gold standard for the imaging of perirectal and pelvic fistulas. With
      the advent of ultrafast MRI small and large bowel imaging has become highly
      attractive and is being advocated more and more in the diagnostic work up of
      inflammatory bowel disease. Imaging protocols include fast T1-weighted gradient
      echo and T2-weighted TSE sequences and oral or rectal bowel distension.
      Furthermore, dedicated imaging protocols are based on breath-hold imaging under
      pharmacological bowel paralysis and gastrointestinal MR contrast agents (Hydro
      MRI). High diagnostic accuracy can be achieved in Crohn's disease with special
      reference to the pattern of disease, depth of inflammation, mesenteric reaction,
      sinus tract depiction and formation of abscess. In ulcerative colitis, the mucosa
      related inflammation causes significantly less bowel wall thickening compared to
      Crohn's disease. Therefore with MRI, the extent of inflammatory changes is always
      underestimated compared to colonoscopy. According to our experience in more than
      200 patients as well as the results in other centers, Hydro-MRI possesses the
      potential to replace enteroklysis in the diagnosis of chronic inflammatory bowel
      disease and most of the follow-up colonoscopies in Crohn's disease. Further
      technical improvements in 3D imaging will allow interactive postprocessing of the
      MR data.

PMID- 11225417
TI  - [Significance of findings of chest X-rays and thoracic CT routinely performed at
      the emergency unit: 102 patients with multiple trauma. A prospective study].
AB  - PURPOSE: To evaluate prospectively whether and to what extent both thoracic
      computed tomography (Tx-CT) and supine X-ray of the chest (Rx-Tx) are able to
      show additional findings that are therapeutically relevant. PATIENTS AND METHODS:
      According to a fixed study protocol, we performed Rx-Tx and Tx-CT in 102
      consecutive, haemodynamically stable polytrauma patients (mean age, 41.2 yrs; age
      range, 12-93 yrs). Findings of therapeutical relevance drawn from both Tx-CT and
      Rx-Tx, and urgent interventions indicated by an attending trauma team were
      documented on a standardized evaluation sheet immediately. Any change in the
      patient's management that is different from routine life-saving procedures, and
      any therapeutical intervention done in the emergency room or elsewhere (operating
      theatre, angiographic facility) were considered therapeutically relevant.
      RESULTS: Of 102 patients, 43 (42.2%) had a total of 51 therapeutically relevant
      findings. Rx-Tx alone yielded 23 relevant findings (45.1%) in 23 patients
      (22.5%). Of them, Tx-CT has shown additional important findings in 7 patients
      (30.4%). When Tx-CT alone is considered, it revealed 22 new findings of
      therapeutical relevance (43.2%) in 20 patients (46.5%). Altogether, Tx-CT was
      able to show 30 relevant findings in 27 patients, i.e., there was a therapeutical
      benefit for 26.5% of all polytrauma patients included. Most frequently, there was
      a need for chest-tube insertion (n = 29). CONCLUSIONS: Polytrauma patients if
      haemodynamically stable may profit from computed tomography of the chest when
      therapeutically relevant thoracic injuries are looked for or early therapeutical
      interventions are to be checked. However, chest X-ray should stay as a "front
      line" screening method because of its superbly quick feasibility and
      availability.

PMID- 11225418
TI  - [Spiral CT of the abdomen: weight-adjusted dose reduction].
AB  - AIM OF THE STUDY: The influence of weight-adjusted current application in spiral
      CT of the abdomen on noise was investigated in a clinical study. PATIENTS AND
      METHODS: In 77 routine abdominal CT investigations (120 kV, 8 mm, pitch 1.5) the
      patients were divided into three body-weight groups A (< 60 kg), B (60-80 kg),
      and C (> 80 kg). The tube current was randomized prospectively in low weight
      group A, either 125 mA or 150 mA, in middle and high weight groups B and C, 150,
      175 or 200 mA, with a tube revolution time of one second. The noise was measured
      in liver, skeleton muscle, fat tissue, and bladder content for evaluation of
      image quality. RESULTS: The bodyweight groups differ significantly in noise,
      e.g., in the liver (150 mA): group A: 15.8 HU, group B: 18.9 HU, group C: 21.5
      HU. The increase of tube current (150, 175, 200 mA) within a body weight group
      resulted in a minor decrease of noise (18.9 HU, 17.6 HU, 17.5 HU, respectively,
      in group B). There is a good correlation of noise with body weight, body mass
      index and body cross section, but not with body size. CONCLUSION: A body weight
      adjusted reduction of tube current is possible without an increase of noise.

PMID- 11225419
TI  - [Value of multiplanar reformations (MPR)in multi-slice spiral CT of the lung].
AB  - PURPOSE: To evaluate the quality of multiplanar reformations (MPR) of
      multidetector spiral-CT (MD-CT) data sets of the chest based on anatomic
      criteria. METHODS: 90 patients with suspected or known diseases of the lung
      parenchyma underwent thoracic MD-CT with 1-mm collimation. Axial scans were
      reconstructed with 1-mm slice width and 0.6-mm reconstruction increment. Coronal
      and sagittal MPRs were reconstructed with 3, 5 and 8 mm thickness from the axial
      scans. Three blinded readers rated image quality based on several anatomic
      criteria and the presence of different artifacts using a 5-point scale. The
      scores for MPRs were compared with those of 5-mm thick axial scans. RESULTS: All
      anatomical structure were equally well depicted on MPRs as on axial scans with
      very good interobserver correlation (kappa 0.69-0.76). Only the lung parenchyma
      directly adjacent to the heart and the great vessels were visualized with limited
      quality due to cardiac pulsation artifacts. Advantages of sagittal MPRs include
      the sharper delineation of interlobar fissures and thus improved anatomic
      localization of a lesion. Coronal reformations also offer improved anatomic
      orientation in comparison with 5-mm axial scans. A slice thickness of 5 mm for
      MPRs yielded best results. CONCLUSIONS: MPRs allow an unrestricted assessment of
      the lung. Sagittal and coronal reformations improve the topographical
      visualization of chest anatomy.

PMID- 11225420
TI  - [Differentiation of serous and purulent fluids in vitro and in vivo by means of
      diffusion-weighted MRI].
AB  - AIM: The aim of this study was to test the feasibility for differentiation of
      serous fluid collections and abscess fluid with diffusion-weighted imaging and to
      compare three different diffusion sequences. MATERIAL AND METHODS: Thirteen
      puncture samples (6 serous, 7 purulent) and 19 patients with either serous fluid
      collections (n = 12) or abscesses (n = 7) were examined with diffusion-weighted
      spin-echo (SE), stimulated-echo (STE), and fatsuppressed SE (SE-SPIR) sequences.
      For in vitro studies 4 different b-factors (0, 87, 355, 798 s/mm2 in SE and SE
      SPIR and 0, 51, 204, 460 s/mm2 in STE) were chosen and the apparent diffusion
      coefficient (ADC) was calculated. For in vivo measurements identical sequences
      with two b-factors (0.598 s/mm2 in SE and SE-SPIR and 0.360 s/mm2 in STE) were
      applied and the normalized signal attenuation was calculated. A navigator-echo
      technique and peripheral pulse triggering was used for motion artifact reduction.
      RESULTS: The in vitro study yielded an ADC of serous fluid, which was close to
      that of free water, whereas for purulent fluid a significantly lower ADC was
      calculated. During in vivo examinations, serous fluids showed a strong signal
      attenuation (down to 22-32% of basic value) compared to a minor signal
      attenuation in purulent fluids (down to 86-94% of basic value) (p < 0.05).
      CONCLUSIONS: In summary, with all three investigated diffusion schemes serous and
      purulent fluids can be clearly differentiated.

PMID- 11225421
TI  - [Dose-dependent effects of the combined beta/gamma emitter 186-Rhenium on the
      growth of human vessel wall cells].
AB  - PURPOSE: The aim of this study was to evaluate the capability of human aortic
      smooth musc e cells (HaSMC) and endothelial cells (EC) to recover after
      incubation with the combined beta/gamma emitter 186rhenium. MATERIALS AND
      METHODS: Two days after plating, HaSMC and EC were incubated for five days with
      186Re (total doses applied 4 Gy-32 Gy). Cell counts were performed for a period
      of 30 days (haSMC) and 22 days (EC). To detect possible growth recovery, colony
      formation assays were plated for both cell types on day 5, 10, and 20 (and lay 30
      for haSMC). RESULTS: Both cell types presented a dose-dependent growth inhibition
      which was maximum at a dose of 32 Gy. Human endothelial cells presented with
      total growth recovery at 4 and 8 Gy, and a partial growth recovery at 16 Gy.
      Smooth muscle cells only presented partial growth recovery at 4 and 8 Gy. At 16
      Gy and more no recovery was detected. CONCLUSION: HaSMC as well as EC growth can
      be modulated effectively with 186Re over a period of 30 days in vitro. Compared
      to smooth muscle cells human endothelial cellls seem to possess a higher
      potential to recover at doses of 8 to 16 Gy. 186Re may be a valuable radionuclide
      to prevent restenosis.

PMID- 11225422
TI  - [Epidermoid or arachnoid cyst: CISS, FLAIR and diffusion images as solution of
      the diagnostic dilemma].

PMID- 11225423
TI  - [Symptoms of prostatitis in German. The Giessen Prostatitis Symptom Score].
AB  - In cases of chronic prostatitis, a systematic case history of subjective
      complaints is crucial. In addition to the urological diagnosis, a special symptom
      questionnaire can be utilized. The objective of this study was to develop a
      standardized and valid questionnaire to assess prostata-specific complaints in an
      economic way. Independently from the evaluation of this questionnaire, a similar
      instrument (CPSI) was developed in the United States with several similar items.
      The Giessener prostatitis symptom score (GPSS) comprises 12 items. Thirty-three
      patients suffering from prostatitis and 770 representatively selected German
      males filled in the questionnaire. A sum score of 6 points proved to best suited
      to differentiate between the patient and the representative group. Values of 6
      and above indicate the corresponding diagnosis, i.e., it can be assumed that
      prostata-specific symptoms occur at least occasionally. In the representative
      sample, 7.8% of the males showed prostata-specific complaints with a score of 6
      or above. A comparison between the GPSS and the CPSI concerning their diagnostic
      validity has not yet been performed. This comparison will show which of the
      instruments is better suited for prostatitis screening.

PMID- 11225424
TI  - [National Institutes of Health (NIH) Chronic Prostatitis Symptom Index. The
      German version].

PMID- 11225425
TI  - [Prostatitis syndrome. Changes in the ejaculate and effects on fertility].
AB  - Inflammation and infections of the male reproductive tract represent an important
      factor in male infertility that is potentially responsive to successful therapy.
      A standardized diagnostic procedure is a prerequisite for the exact evaluation of
      alterations of ejaculate specimens, especially in cases of the different forms of
      the prostatitis syndrome. Several alterations in ejaculate due to inflammation
      and infection have been identified that have a negative impact on the quality of
      sperm. Besides the influence of leuko- and bacteriospermia, the effect of
      inflammatory mediators, such as cytokines and reactive oxygen species (ROS), are
      being discussed as relevant pathomechanisms. These parameters just recently were
      incorporated into the conventional range of diagnostic criteria. Clinical studies
      that investigate the quality of ejaculate in the different forms of the
      prostatitis syndrome yielded contradictory results. Only antimicrobial therapy
      has been sufficiently described as a therapeutic option. In the future, it will
      be decisive to include novel functional and molecular parameters to define an
      interaction of urogenital infection and male infertility.

PMID- 11225426
TI  - [Therapy of prostatitis syndrome].
AB  - The chronic prostatitis syndrome is a multifactorial disease of mainly unknown
      etiology. Quite different therapeutic options are therefore recommended.
      According to the new NIH classification only in acute and chronic bacterial
      prostatitis pathogens can be cultured. A long-term antimicrobial therapy, mainly
      with fluoroquinolones, is therefore recommended. Most of the patients, however,
      suffer from a chronic pelvic pain syndrome (CPPS) which can be subdivided into an
      inflammatory and a non-inflammatory CPPS. Whether the inflammatory CPPS is an
      infectious disease, remains uncertain. An antibiotic therapy therefore is not the
      first choice. Several patients, however, have been improved by such a therapy,
      especially in combination with alpha-receptor blockers. In case of proven or
      suspected functional obstruction of the bladder neck long-term treatment with
      relatively high dosages of alpha-receptor blockers is recommended. In case of
      failure other treatment modalities, including psychosomatics, may be applied, of
      which usually only results of sporadic reports but not of controlled studies are
      available. It is important, however, to keep the patient fully informed about the
      diagnostic and therapeutic problems not to interfere with a trustful therapist
      patient relationship.

PMID- 11225427
TI  - [Antegrade percutaneous endoluminal therapy of nonmalignant strictures of
      ureterointestinal anastomoses after urinary diversion].
AB  - We report our experience on the use of antegrade percutaneous incision of
      ureterointestinal anastomosis strictures after urinary diversion. Since 1994, we
      evaluated 9 patients with 12 ureterointestinal anastomosis (UAS) strictures who
      were treated with a cold-knife incision. After placement of an 8-Fr nephrostomy
      tube, a 0.035-in guide wire was passed through the stricture under guidance of a
      central opened ureter catheter (5 Fr). A wire-mounted cold-knife was pulled
      through the strictured area in the retrograde way under fluoroscopic control.
      Routinely, following the incision, an 8-Fr external stent was left in place for 6
      8 weeks. After removal of the stent, the ureteroenteric area remained patent in 7
      UAS (58%) cases versus 7 of 9 (78%) patients, with average follow-up of 18 months
      (range 13-25 months). Failures were associated with radiogenic injury of the
      ureter in three UAS cases and unexplained in two. No complication was observed.
      Percutaneous endourological management of ureterointestinal anastomotic
      strictures with the cold-knife incision is a safe and effective alternative to
      open surgical repair and should be tried as an initial approach.

PMID- 11225428
TI  - [Chronic prostatitis--will we find a solution to the dilemma?].

PMID- 11225429
TI  - [Sachse internal urethrotomy. Is erectile dysfuction a possible complication?].
AB  - Erectile dysfunction is reported to be a complication of direct-vision internal
      urethrotomy by some authors in 2.2-10.6% of cases. It is caused by injury to the
      cavernous nerve by direct severance with the cutting blade, late fibrosis after
      extravasation and infection, or by a shunt between the corpora cavernosa and
      corpus spongiosum. The aim of this examination was to evaluate all internal
      urethrotomy patients from 1990 to 1999, regarding this kind of complication. Of
      184 patients, 111 had to be excluded due to preexisting erectile dysfunction,
      malignancy, age over 75 years, or open surgery of the urethra before internal
      urethrotomy. Five patients died. Of 184,68 patients did not have erectile
      problems before the operation and only one complained about erectile dysfunction
      following direct-vision internal urethrotomy. Further examination showed an
      impaired arterial inflow in both arteriae penis profunda; cavernosography could
      not prove a shunt between the corpora cavernosa and corpus spongiosum. Erectile
      dysfunction is a possible complication of direct-vision internal urethrotomy.
      External sphincterotomy at the 3- and 9-o'clock position, urethrotomy after
      injury or open reconstructive surgery of the urethra, and urethrotomy of long and
      dense strictures as well as a dilatation over 22 Chr. are known to cause this
      complication. To inform the patient concerning this kind of complication is
      recommended before urethrotomy.

PMID- 11225430
TI  - [Etiopathogenesis of prostatitis]].
AB  - The first step in adopting a practical approach to the management of patients
      with prostatitis lies in the realization that the etiology of the symptoms often
      remains unclear and the traditional etiologically based classification system is
      part of the problem and not the solution. This problem was recognized in 1995 by
      the National Institutes of Health Consensus Conference on prostatitis. It was
      suggested that the classification of this disease be changed. The traditional
      categories "chronic nonbacterial prostatitis" and "prostatodynia" were replaced
      by the new category "chronic pelvic pain syndrome." The introduction of the term
      "syndrome" reflects two issues: despite lack of evidence for bacterial
      involvement based on conventional methods, nonbacterial prostatitis may indeed
      still be an infectious disease, and the etiology of the symptoms may be caused by
      a disorder not related to the prostate gland alone.

PMID- 11225431
TI  - [Autosomal dominant polycystic kidney disease. Case report of a 20 kg polycystic
      kidney].
AB  - Polycystic kidneys can reach huge dimensions as a result of their continuous
      growth and thus lead to a "mechanical problem." We report on a 69-year-old
      patient with enormous polycystic kidneys having been treated for 4 years with
      standard hemodialysis. In the last 12 months, the patient was suffering from a
      deterioration of his condition and progressively developed cachexy. The
      preoperative status of the multi-morbid patient jeopardized operability. It was
      decided to perform bilateral nephrectomy with a Chevron incision on the right
      side. The right kidney weighed 11 kg, the left 9 kg. There were no postoperative
      problems. The massive relief resulted in an impressive improvement of this risk
      patient's fitness and quality of life. There is a clear indication of unilateral
      nephrectomy in case of a renal transplantation. The role and necessity of a
      bilateral nephrectomy in the event of polycystic kidneys is discussed based on
      the respective literature.

PMID- 11225432
TI  - [Adrenalectomy within the scope of tumor nephrectomy?].
AB  - In urology, renal cell carcinoma is the third most frequently diagnosed
      malignancy. Localized, non-metastatic tumors are generally cured by radical tumor
      nephrectomy. Since the 1960s, this procedure has routinely included removal of
      the kidney together with the perirenal fat, Gerota's fascia, and ipsilateral
      adrenal gland. In recent years, improved diagnostic methods have led to the
      detection of tumors at earlier stages. These methods widen the scope for organ
      sparing surgical strategies and have consequently sparked controversy over
      adrenal gland removal. Despite this, radical tumor nephrectomy that includes
      adrenal gland removal is still strongly advocated. This is the only suitable
      surgical approach for the cure of patients with direct tumor infiltration of the
      adrenal gland. In the case of adrenal involvement, minimal tumor dimension and
      the predisposing localization of the primary tumor have to relevance. The imaging
      procedure for diagnosis is also difficult to assess, especially in slim patients
      with upper role tumors. Finally, to date, no justifiable disadvantages of
      adrenalectomy have been described.

PMID- 11225433
TI  - [Adrenalectomy within the scope of tumor nephrectomy--overtreatment?].
AB  - Metastatic spread to the ipsilateral adrenal gland occurs in 1.2-10% of patients
      with renal cell carcinoma (RCC). In the majority of these cases, the primary
      tumor is locally advanced with poor differentiation, venous invasion, and
      involvement of the regional lymph nodes. Adrenal metastases are usually detected
      preoperatively by CT scan or MRI. Adrenal metastases are indicators of systemic
      disease with poor prognosis quo ad vitam. Only 0.5-2.3% of patients with RCC and
      adrenal metastases are free of venous invasion or lymphatic disease. In this
      small subset of patients, cure is possible by surgical removal of the adrenal
      gland. In 97.7-99.5% of patients with RCC, ipsilateral adrenalectomy has no
      impact on their prognosis. We therefore conclude that this procedure should be
      performed only if there is radiological suspicion of an adrenal mass.

PMID- 11225434
TI  - [Nobel Prize in medicine 2000. Communicating nerve cells].

PMID- 11225435
TI  - [Good clinical practice. Significance for clinical research].

PMID- 11225436
TI  - [Guideline for perioperative prevention in interventions on the urinary tract and
      male genitalia. German Society of Urology]].

PMID- 11225438
TI  - [Pathology for the 21st century. Invitation to the 85th Congress of the German
      Society for Pathology in Munster, 6-9 June 2001].

PMID- 11225437
TI  - [Diagnosis of chronic prostatitis].
AB  - The new classification of prostatitis syndromes by the National Institutes of
      Health clearly defines the diagnostic criteria for categorization according to
      the clinical symptoms. In addition to the validated symptom scores, the four
      glass test demonstrating increased numbers of leukocytes and/or bacteria serves
      for differentiating between the symptoms. Increased levels of leukocytes and/or
      increased bacterial count in expressed prostatic excretion (EPS) are typical of
      prostatitis, although there is a high degree of correspondence with the VB3
      fraction (urine voided after prostatic massage). The detection of peroxidase
      cells (granulocytes) and of an increased concentration of polymorphonuclear (PMN)
      leukocyte elastase in the ejaculate are indicative of uroadnexitis. Nonbacterial
      forms of prostatitis (NIH III) and increased PSA levels require intensive
      clinical diagnosis.

PMID- 11225440
TI  - [Active pre-atrophic autoimmune gastritis. A practice-oriented concept for
      diagnosis and treatment].
AB  - Helicobacter pylori infection sometimes leads to an antigastric autoimmunity that
      ultimately develops into complete atrophy of the glands of the gastric mucosal
      glands. It has been found that the "classical" parietal cell antibody positive
      and H. pylori induced autoimmune gastritis share common aspects of
      histomorphology, stages, and pathomechanisms. Healing of H. pylori associated
      active preatrophic autoimmune gastritis by eradication treatment has been
      confirmed both in case reports and in prospective and retrospective studies. This
      leads to a general practice-oriented four-step concept for diagnosis and
      treatment in daily routine: (a) Histological work-up on the basis of: lymphocytic
      infiltration of the glands of the corpus and fundic mucosa, focal destruction in
      individual corpus glands, reactive hypertrophy of the parietal cells, and search
      for H. pylori. (b) Additional serological work-up if histological evidence of H.
      pylori is lacking: determination of H. pylori and parietal cell antibodies in the
      serum. (c) Initiation of an established H. pylori eradication therapy if
      histology and/or serology is positive for H. pylori. (d) Histological and
      serological follow-up for 9-12 months to monitor the results of treatment.

PMID- 11225439
TI  - [Extent, topography and symptoms of Helicobacter pylori gastrtitis. Phenotyping
      for accurate diagnosis and therapy?].
AB  - Helicobacter pylori gastritis, a very common condition, may lead to serious
      sequelae such as peptic ulcer, gastric carcinoma, and mucosa-associated lymphoid
      tissue lymphoma. Histological grading of the various gastritis parameters can
      help to identify the risk of these sequelae and thus improve the indication for
      prophylactic treatment of the H. pylori infection. This applies in particular to
      two types of "risk gastritis": gastritis of the duodenal ulcer phenotype and
      gastritis of the carcinoma phenotype. In the former the antrum shows pronounced
      inflammatory changes while only low-grade gastritis is seen in the corpus. In the
      latter, by contrast, the gastritis in the corpus is at least equally as severe as
      that in the antrum; in addition, intestinal metaplasia and focal atrophy is also
      frequently found in this phenotype. By establishing topographic grading of the
      gastritis in antrum and corpus the pathologist can therefore play the role of a
      "litmus test" for prophylactic H. pylori eradication treatment.

PMID- 11225441
TI  - [Helicobacter pylori and antigastric autoimmunity].
AB  - Recent studies report a significant association between Helicobacter pylori
      gastritis and autoimmune reaction. Antigastric autoantibodies are detectable in
      about 30% of H. pylori infected patients. Two major in situ binding sites have
      been found: first, at the luminal membrane of the foveolar epithelium in antrum
      and corpus mucosa and, second, at canalicular membranes within parietal cells in
      the corpus mucosa. The presence of latter type of autoantibodies is correlated
      with histological and clinical parameters of corpus mucosa atrophy. The gastric
      H+/K(+)-ATPase, which is already known as an autoantigen in classic autoimmune
      gastritis, also represents a major target in atrophic H. pylori gastritis.
      According to recent data molecular mimicry between H. pylori and the host does
      not play a pathogenic role in the formation these autoantibodies. In conclusion,
      antigastric autoimmunity represents a relevant host factor which contributes to
      the final outcome of H. pylori gastritis.

PMID- 11225442
TI  - [Precancerous risk markers in Helicobacter pylori gastritis].
AB  - Primarily on the basis of epidemiological evidence, Helicobacter pylori was
      classified as a definite human carcinogen in 1994. Although several
      pathophysiological consequences of chronic H. pylori gastritis have been
      identified which may contribute to the development of gastric carcinoma, it is
      still largely unknown why only a minority of individuals infected with H. pylori
      (approximately 1/1000) develop this fatal disease. In recent years many studies
      have examined potential risk factors of H. pylori gastritis to improve our
      understanding of the early events in gastric carcinogenesis. The present paper
      summarizes research data supporting the following hypotheses: (a) Some H. pylori
      possess virulence factors which may contribute to the pathogenicity of the
      organism and may increase the risk for subsequent severe gastroduodenal diseases
      such as gastric cancer. However, the associations between these virulence factors
      and disease is not specific, and may vary considerably among different geographic
      regions. (b) Chronic H. pylori gastritis induces several pathophysiological
      alterations which may promote cancer development. In particular, the corpus
      dominant phenotype of H. pylori gastritis is strongly associated with gastric
      cancer. (c) A family history of gastric cancer per se, but also in combination
      with H. pylori infection, is associated with histopathological and molecular
      alterations that are considered relevant in gastric carcinogenesis.

PMID- 11225443
TI  - [Carrent state of molecular pathology of stomach carcinomas].
AB  - Gastric carcinoma is one of the commonly diagnosed malignancies and remains an
      important cause of mortality in the Western hemisphere. Various sequences of
      genetic alterations may be responsible for the development of gastric cancer, as
      there exist two histological types: well-differentiated or intestinal-type and
      poorly differentiated or diffuse-type gastric cancers. While new genetic findings
      open new perspectives on carcinogenesis and molecular biology of gastric cancer,
      they have not been widely applied in routine diagnostic procedures,
      classification systems, disease monitoring, or prognostic assessment. We discuss
      the mechanisms molecular pathology in relation to their potential clinical
      relevance.

PMID- 11225444
TI  - [The new "Vienna Classification" for epithelial neoplasia of the gastrointestinal
      tract. Pros or cons?].
AB  - A number of seminars have shown considerable differences between Japanese and
      Western pathologists in the the diagnostic differentiation of regenerative
      changes, dysplasia, and well differentiated adenocarcinoma in gastroenterological
      biopsy material. Lesions which most Western pathologists identify as "dysplasia"
      are often considered adenocarcinomas in Japan. A comparison of the biopsy-based
      diagnoses with those established in resected mucosa, however, reveals appreciable
      diagnostic inexperience on the part of Western pathologists, with significant
      discrepancies between their diagnoses based on biopsies and those based on
      resected material. Against this background, a new classification of epithelial
      neoplasias of the gastrointestinal tract was drafted on the occasion of the World
      Congress of Gastroenterology in Vienna in 1998. By collapsing the diagnoses "high
      grade adenoma/dysplasia, noninvasive carcinoma (carcinoma in situ), and suspected
      invasive carcinoma" into a single category ("noninvasive high-grade neoplasia,"
      category 4), this scheme should largely eliminate the diagnostic discrepancies
      between Western and Japanese pathologists. As with every classification, the
      Vienna classification has its advantages and disadvantages; these are discussed
      here. The most important advantage of the Vienna classification is that the
      various categories are associated with different recommendations for further
      diagnostic and therapeutic measures. This applies particularly to category 4,
      with the recommendation for only local treatment initially (endoscopic mucosal
      resection or surgical excision). Since the introduction of the Vienna
      classification the new WHO classification of neoplasias of the gastrointestinal
      tract has recently been published, in which the term dysplasia has been replaced
      by "intraepithelial neoplasia." This means that the Vienna classification needs
      to be modified accordingly.

PMID- 11225445
TI  - [Chemical-reactive gastritis].
AB  - Chemical or reactive gastritis is commonly induced by endogenous substances such
      as bile and pancreas secretions, but can it also be caused by exogenous noxious
      substances, including acetylsalicylic acid, nonsteroidal anti-inflammatory drugs,
      chemotherapeutics, and alcohol. The histopathological patterns are similar,
      involving epithelial damage extending up to erosions with consecutive
      regenerative hyperplasia and damage to capillaries, with edema, hemorrhage, and
      proliferation of smooth muscles. As cellular infiltrates are minimal or lacking,
      some authors have proposed the term "gastropathy" instead of the term chemical or
      reactive gastritis as proposed by the updated Sydney classification. This
      contribution describes the different patterns and grades and discusses their
      pathogenesis. Mixed forms of chemical/reactive gastritis and other forms of
      gastritis are also described, for example, that from Helicobacter.

PMID- 11225446
TI  - [Lymphocytic gastritis--a rare disorder of the gastric mucosa].
AB  - Lymphocytic gastritis, first described by Haot et al. in 1986, is a very rare
      form of gastritis (0.8-1.6% of cases) with unclear pathogenesis. On endoscopy,
      lymphocytic gastritis may present either a normal appearance, such as gastritis
      varioliformis with multiple elevated chronic erosions in the corpus and fundus,
      or as a giant fold gastritis in the corpus and fundus. This type of gastritis is
      diagnosed histologically based on an accumulation of intraepithelial lymphocytes
      (more than 25/100 epithelial cells) in the surface cells of the gastric mucosa.
      Its etiopathogenesis is currently thought to be a sprue-associated reaction or an
      atypical reaction to Helicobacter pylori infection. Some studies report the
      lymphocytic gastritis in almost 45% of cases of sprue, with the gastritis
      regressing in response to a gluten-free diet, while others report a correlation
      of lymphocytic gastritis with serologically and/or histologically confirmed H.
      pylori infection, with the lymphocytic gastritis being cured by H. pylori
      eradication treatment in a high percentage of the cases. It is possible that a
      similar abnormal immune reaction to an inflammatory agent underlies both
      pathological entities, sprue and lymphocytic gastritis--in the one case gluten
      and in the other H. pylori--which would mean that sprue-induced and H. pylori
      induced forms of lymphocytic gastritis exist side by side.

PMID- 11225447
TI  - [50 years of Barrett esophagus. Current diagnostic possibilities in pathology].
AB  - The most important differential diagnosis of specialized intestinal columnar cell
      metaplasia (Barrett's-mucosa) is the intestinal metaplasia of the cardia mucosa
      (possibly caused by Helicobacter infection). Furthermore it happens from time to
      time that Barrett's regenerative epithelium is overdiagnosed as low-grade
      dysplasia (unequivocal intraepithelial neoplasia). This might explain the
      disappearance of many low-grade dysplasias during further follow-up. Mucosal
      adenocarcinomas are often underdiagnosed as dysplastic lesions. Therefore many
      authors tried to establish molecular methods for improvement of the diagnostic
      possibilities. Immunohistochemistry or PCR with p53 and HER 2-neu might give at
      least some help but a negative reaction does not exclude a neoplasia in every
      case. The gold standard is careful endoscopy and biopsy taking with good
      documentation of the endoscopical findings and most important still the routine
      H&E stain are the only reliable diagnostic tools.

PMID- 11225448
TI  - [Diagnosis of celiac disease and sprue. Recommendations of the German Society for
      Pathology Task Force on Gastroenterologic Pathology].
AB  - The diagnosis of celiac disease (CD) is based upon histological findings in
      duodenal or jejunal biopsy specimens. In recent years it has been seen that the
      development of CD lesion in the small bowel is a dynamic process which may
      present in various histological forms. At one end of the spectrum is a mucosa
      with normal architecture and an increase in intraepithelial lymphocytes; at the
      other end is the classical flat mucosa. Histological features supporting the
      diagnosis of CD are architectural changes of the villi and/or crypts, an increase
      in lamina propria cell density, and an increase in intraepithelial lymphocytes
      counts. Exact histological classification of the histological findings is
      required for diagnostic purposes and for monitoring of CD patients. This has
      become possible by using a modified Marsh classification. We present both the
      histological presentation of CD and the modified Marsh classification, and the
      most important differential diagnoses.

PMID- 11225449
TI  - [Whipple's disease. Histologic diagnosis after the discovery of Tropheryma
      whippelii].
AB  - Since the microbiological discovery of Tropheryma whippelii, Whipple's disease
      has attracted to new attention in clinical medicine. As small intestinal biopsy
      is the diagnostic procedure, the impact of knowledge about the histopathological
      features of Whipple's disease and its differential diagnosis has increased. PAS
      positive macrophages in the intestinal mucosa are the diagnostic hallmark, but
      further subtyping of cells is important. In Whipple's disease macrophages with
      intensely PAS-positive granular particles in the cytoplasm (type 1) should be
      distinguished from cells with faintly PAS-positive cytoplasm without granular
      particles (type 3). The latter type of macrophages may persist even for many
      years but does not affect a diagnosis of intestinal remission. However, as
      systemic infection with T. whippelii is common, but intestinal biopsy specimens
      are not representative for other organs, additional investigations are performed.
      These include analysis of the cerebrospinal fluid by means of cytology and
      polymerase chain reaction, even in patients without neurological symptoms. For
      ascertaining eradication of T. whippelii in the cerebrospinal fluid, polymerase
      chain reaction is more reliable than cytology.

PMID- 11225450
TI  - [Microinvasive laparoscopic cholecystectomy with 2 mm instruments. Presentation
      of the method and initial results].
AB  - Between September 1998 and May 1999, 498 patients underwent laparoscopic
      cholecystectomy. Of these, 301 patients were electively scheduled cases. Two
      hundred and sixty-seven patients (58.4%) patients were operated on with the
      standard laparoscopic technique (LC) and 34 (6.8%) with a new microinvasive
      technique (MLC) using self-developed 2-mm instruments. The technique of this
      microinvasive method is introduced and the first results are reported. These
      results encourage us to recommend our new method for selected cases.

PMID- 11225451
TI  - [Adjustable silicone gastric banding (ASGB, Bioenterics) and the Swedish
      adjustable gastric banding (SAGB, Obtech) in treatment of morbid obesity].
AB  - INTRODUCTION: Two different adjustable silicone gastric bandings were
      laparoscopically applied and compared regarding per- and postoperative
      complications and successful weight loss. PATIENTS AND METHODS: A total of 120
      consecutive patients received a laparoscopic adjustable gastric banding and were
      prospectively documented. In the learning phase (LP) 50 patients were treated
      with an Adjustable Silicone Gastric Banding (ASGB, Bioenterics) using an
      intragastric balloon calibration technique according to Belachew. Group I (n =
      29) received the same band using a surgical technique with tunneling behind the
      oesophagus towards His' angle, while the second group (n = 41) received a Swedish
      Adjustable Gastric Banding (SAGB), using the same technique as in group I. A BMI
      of > 35, complications secondary to obesity and failed diets were the indication
      for the operation. Thirty patients were male, 90 female, with a mean age of 37
      years (18-60). RESULTS: In the LP 8 patients had to be reoperated (16%) for band
      slippage and/or pouch dilatation, in group I 6 (19%) and in group II 1 (3%) (P =
      0.02, II vs I). The mean hospital stay was 3.7 +/- 0.5, 3.4 +/- 0.8 and 3.3 +/-
      0.4 days in LP, I und II, respectively. LONG-TERM RESULTS: After a mean of 24
      months (19-42) the loss of body weight was 8.4 kg after 3, 13.9 kg after 6, 22.1
      kg after 12 and 27.8 kg after 18 months in the LP. In group I after a mean of 14
      months (12-19) 10.3 kg after 3, 18.7 kg after 6, 24.8 kg after 12 months. In
      group II after a mean of 10 months (6-16) the loss of body weight was 7.9 kg
      after 3 and 19.4 kg after 6 months. CONCLUSION: In our experience it appears that
      the SAGB is easy to handle and less prone to complications such as dysphagia and
      slipping, probably due to good fixation of the band due to its width. A
      prospective randomized trial is warranted.

PMID- 11225452
TI  - [Outcome of minimally invasive surgery. Qualitative analysis and evaluation of
      the clinical relevance of study variables by the patient and physician].
AB  - INTRODUCTION: Mechanistic study endpoints, evaluated exclusively by the
      physician, are mostly used in clinical studies evaluating new treatment
      modalities (e.g. laparoscopic cholecystectomy). Those endpoints often lack
      clinical relevance. The patient's opinion concerning the importance of a study
      endpoint is particularly important in the evaluation of minimally invasive
      procedures, which place special emphasis on patient comfort. METHODS: In a first
      step it was evaluated by meta-analysis, which clinical endpoints have been used
      for comparison of laparoscopic and conventional cholecystectomy. Furthermore,
      using a qualitative analysis it was investigated how important the individual
      study endpoints are for patients and physicians. Ten patients and five surgeons
      were questioned in a structured interview. RESULTS: Of all outcome variables used
      world-wide, approximately one third were hermeneutic study endpoints, depending
      on the quality of the study, but often the method of evaluation was insufficient.
      Only three of 215 endpoints (< 2%) were quality of life scores, an integrated
      concept of outcome was missing completely. The qualitative analysis confirms the
      claimed difference between isolated and integrated evaluation of treatment goals.
      The importance of postoperative death is underestimated by patients and
      physicians; postoperative pain is overestimated. Patients ranked the outcome
      variable "restoration of full physical fitness" as the most important study
      endpoint after avoidance of complications and death. It is underestimated in
      isolated evaluation and has not been used in the world literature at all.
      CONCLUSION: The analysis of clinical relevance of study endpoints should be the
      first and not the last step of studies to evaluate surgical technology. It cannot
      be based purely on intuition; it must make use of scientifically accepted
      techniques (e.g. qualitative analysis).

PMID- 11225453
TI  - [2-year evaluation of a cooperation model between a surgical university clinic
      and a general hospital].
AB  - INTRODUCTION: On 1 January 1998 a cooperation between an university hospital and
      a peripheral general hospital was initiated with the aim of reducing waiting
      lists and health care costs. Surgical patients initially referred to the
      Department of Visceral and Transplantation Surgery of the University of Bern
      (Inselspital) were evaluated and selected in the outpatient clinic for an
      operation in the peripheral hospital Grosshochstetten. The operation and
      postoperative care in Grosshochstetten was performed by a team from the
      university department according to the standard concept also utilized at the
      university hospital. RESULTS: The 574 patients referred to the university and
      operated on in Grosshochstetten during a 2-year period had a morbidity rate of
      3.5%, a reoperation rate of 1.0% and a mortality rate of 0.15%. The mean hospital
      stay was 6.3 days. The quality evaluation performed by questionnaires to patients
      and physicians showed an overall satisfaction rate of 95%. The cooperation
      resulted in reduction of the overall costs in both hospitals, and the patients'
      involved health insurances profited from substantially lower costs per case.
      CONCLUSIONS: Health care costs in both hospitals as well as the waiting list at
      the university hospital were markedly reduced during this 2-years trial, with an
      overall satisfaction rate of 95%. This form of cooperation of an university with
      a peripheral hospital represents a new and valuable model for effective reduction
      of health care costs.

PMID- 11225454
TI  - [Multi-modality therapy concept in metastatic follicular thyroid carcinoma with
      hyperthyroidism].
AB  - The coincidence of hyperthyroidism and thyroid carcinoma seldom occurs. Only few
      reports on functionally metastases of thyroid carcinoma have been published. We
      report a 59-year-old man who underwent subtotal thyroidectomy for toxic nodular
      goiter. Histological examination revealed a follicular thyroid carcinoma. After
      thyroidectomy and cervical lymphadenectomy the patient developed a strong
      hyperthyreosis. Scintigraphy showed strong radioiodine uptake in the sacrum. De
      bulking resection of the metastasis followed by high-dose radioiodine treatment
      was performed. After radioiodine therapy the patient became euthyroid. Treatment
      of hyperthyreosis in metastatic thyroid cancer requires a multimodal therapeutic
      concept.

PMID- 11225455
TI  - [Routine use of abdominal ultrasound and epigastric CT in polytrauma. Analysis
      oftherapeutic relevanc in 105 patients].
AB  - INTRODUCTION: A prospective analysis was done to determine the frequency of
      therapy relevance of abdominal computed tomography (CT) in multiple trauma
      patients in comparison to abdominal ultrasound (US). METHODS: We recorded all
      multiple trauma patients in the emergency room (n = 248) from August 1996 to July
      1997 with an evaluation form and performed abdominal CT subsequent to US whenever
      the patient was hemodynamically stable and not in need of immediate surgery (n =
      105). We documented the results of both methods and their impact on acute
      therapy. RESULTS: In 27 of 105 patients (25.7%) therapy management was influenced
      by both either US or CT. 76 patients (72.4%) showed normal US findings, followed
      by a CT which showed additional findings with therapeutic relevance in five
      patients (6.6%). Twenty-nine patients (27.6%) showed abnormal US findings.
      Compared to the therapeutic procedures proposed after the use of US the
      subsequently performed CT led to a change in therapy in 12 patients (41.4%).
      CONCLUSION: We conclude that if US is normal, additionally performed CT of the
      abdomen provides information of therapeutic relevance in only a limited number of
      cases. If US is abnormal, CT will have an important impact on therapy in a high
      number of patients.

PMID- 11225456
TI  - [Colo-anal anastomosis: improvement of early function outcome by reconstruction
      with the colonic pouch].
AB  - INTRODUCTION: Early functional outcome after ultra-low anterior resection with
      coloanal anastomosis (CAA) may be improved by construction of a colonic pouch.
      The aim of this prospective observational study was to compare results of colonic
      pouch-anal anastomosis (CPAA) with conventional CAA including the learning curve.
      METHODS: From February 1996 through May 1998, 45 consecutive patients underwent
      CAA or CPAA following radical rectal resection for cancer. The technique of
      resection was identical in both groups, and all patients received a diverting
      stoma. The colonic pouch was constructed using linear staplers. Three and 12
      months following stoma closure subjective continence and bowel habits were
      assessed; anal manometry was performed at 3 months. RESULTS: 20 patients with
      CPAA (9 F, 11 M, age 62 +/- 9 years) were compared to 25 CAA patients (11 f, 14
      m, age 64 +/- 10 years). There was no mortality, and morbidity was comparable
      between groups. Three months following stoma closure, in the CPAA group bowel
      frequency was significantly diminished (1.4 vs 5.8; P < 0.0001), fewer patients
      had liquid motions (0/20 vs 12/25 patients; P < 0.0001), and more were continent
      (20/20 vs 4/25; P < 0.001) and able to defer defaecation (20/20 vs 2/25; P <
      0.0001). Functional anal canal length was significantly shorter in CPAA patients
      (2.9 vs 3.5 cm; P < 0.008). Although at 12 months follow-up continence had
      improved in patients with CAA, bowel frequency (2.5 vs 1.3; P < 0.002), and
      number of patients with liquid motions (10/25 vs 0/20; P < 0.007) and passive
      incontinence (12/25 vs 0/20; P < 0.0001) were still significantly higher than the
      CPAA group. CONCLUSION: Even including the learning curve, CPAA may yield
      superior functional results at 3 months and 1 year compared to conventional CAA
      without increasing morbidity.

PMID- 11225457
TI  - [The diagnostic concept of acute infection of the shoulder joint].
AB  - INTRODUCTION: It is generally accepted that septic conditions of the shoulder
      often lead to an earnest situation with joint damage. Because of the low
      incidence of shoulder infections there are only a few cases reported in the
      literature. Therefore, unlike joint infections of the knee no diagnostic and
      therapeutic standard procedure is documented for the shoulder. MATERIALS AND
      METHODS: In a retrospective study the results of 15 patients with a surgical
      revision at the BG-Clinic-Bergmannsheil-Bochum between 1 January 1989 and 31
      August 1999 after an infection of the shoulder joint were analyzed. We registered
      the following parameters: etiology, intervall until the first clinical symptoms,
      clinical signs, diagnostic procedure, intraoperative site (Gachter
      classification), and operative treatment. The diagnostic procedure followed an
      algorithm, including CRP-determination, ultrasound of the shoulder, ultrasound
      guided aspiration and a Gram stain. If the result was positive, surgical joint
      revision followed. The infection stage was classified intraoperatively according
      to the criteria of the Gachter classification. Eight patients were reexamined
      after an average follow-up of 4.8 years. RESULTS: Fourteen infections followed
      injection. All patients demonstrated increasing CRP levels and a painful limited
      range of motion. In all Gram stains we detected bacterial organisms. The
      diagnosis of an acute infection according to the criteria of this diagnostic
      algorithm was verified intraoperatively in all 15 joints. Two patients with
      delayed admission died postoperatively due to septic multiorgan failure despite
      maximal treatment under intensive care conditions. CONCLUSION: If there are
      suspicious clinical symptoms after a typical anamnesis, we recommend an immediate
      diagnostic algorithm, including CRP determination, ultrasound of the shoulder,
      ultrasound-guided joint puncture and a Gram stain. If there is acute joint
      infection, time-consuming diagnostic procedures must be avoided because of the
      risk of secondary reduced joint mobility or life-threatening complications.

PMID- 11225458
TI  - [Laparoscopic Toupet partial fundoplication as general surgical therapy of
      gastroesophageal reflux. 1-year results of a 5-year prospective long-term study].
AB  - INTRODUCTION: A variety of laparoscopic antireflux operations exist for patients
      with gastroesophageal reflux diseases (GERD). Most surgeons operate using the
      concept of "tailored approach", which depends on esophageal motility. We have
      abandoned this concept because of the relatively high incidence of wrap-related
      complications in patients treated with laparoscopic Nissen fundoplication
      compared with patients treated with partial fundoplication. It is our policy to
      perform laparoscopic Toupet partial fundoplication in all patients suffering from
      GERD, independent of their esophageal motility. METHODS: In a prospective trial
      we have assessed and evaluated our 1-year results of the first 100 consecutive
      patients treated with Toupet partial fundoplication. All patients underwent
      esophagogastroscopy and 24-h pH manometry before operation. One third of patients
      (n = 34) underwent control manometry 8 weeks postoperatively. The patients were
      followed up clinically 1, 2, 6 and 12 months postoperatively. RESULTS: In this
      study group we achieved a healing rate in GERD of 97%. In 3% of patients GERD
      recurred. The median clinical DeMeester score decreased from 4.27 +/- 1.5 points
      preoperatively to 0.25 +/- 0.5 points 1 year postoperatively (P < 0.0005). The
      median fractional time with pH < 4 decreased from 17.8% +/- 12.5% preoperatively
      to 0.9% +/- 1.2% 8 weeks postoperatively (P < 0.0005). Because of persistent
      dysphagia 5% of our patients required postoperative dilatation therapy. The rate
      of reoperation and mortality was 0%. The total morbidity rate was 18%. In 50% of
      patients with preoperatively recorded esophageal motility disorder, an
      improvement of esophageal motility was found postoperatively. CONCLUSIONS: Our 1
      year results encourage us to continue to perform laparoscopic Toupet partial
      fundoplication as the primary repair in all GERD patients, independent of their
      esophageal motility. Laparoscopic Toupet partial fundoplication has proven to be
      a safe and highly successful therapeutic option in these patients.

PMID- 11225459
TI  - [Effectiveness of an improved antiseptic in treatment of contaminated soft tissue
      wounds].
AB  - A novel antiseptic biguanide has been shown to be more bactericidal and tissue
      compatible in vitro than other antiseptics. In our controlled, prospective and
      randomized double-blind study on patients with bacteria-contaminated wound types
      2-4, one group (n = 45) was treated with humid cotton swab dressings of 0.2%
      Lavasept solution compared with Ringer solution (n = 35). No deterioration of
      wound healing was observed in either group. Lavasept treatment resulted in faster
      and significant reduction of gram-positive germs. The tissue compatibility of
      Lavasept was evaluated as significantly better than Ringer solution.

PMID- 11225460
TI  - [Intra-abdominal lymphangioma].
AB  - Mesenteric cystic tumors are very rare. The incidence of the cystic lymphangioma,
      which belongs to this group, is even lower. Often it is mistakenly classified
      together with the chylous mesenteric cysts. The term "mesenteric cyst" is of a
      descriptive topographical nature, whereas the lymphangioma can be classified
      clearly by the histopathological findings. The lymphangioma typically appears in
      the first decade and when it is intra-abdominal it shows acute abdominal
      symptoms. Ultrasonography and computed tomography are very sensitive but not very
      specific examinations. The differential diagnosis of intra-abdominal lymphangioma
      includes many benign and malignant tumors. Therefore, a diagnosis is often first
      made during operation because of the macroscopic aspect and then definitely
      because of the histological examination. Differentiation between a mesenteric
      cyst and a cystic lymphangioma is important for the prognosis, because when there
      is a cystic lymphangioma with an incomplete resection, one has the danger of a
      recurrence with tendency to invasive growth. The therapy of choice is a complete
      radical resection. We report the case of an intra-abdominal lymphangioma and have
      studied the reports published about these tumors. We point out the clinical
      presentations, diagnosis, differential diagnosis and therapy of the lymphangioma.

PMID- 11225461
TI  - [Pseudoaneurysm of the hepatic artery--a rare complication after orthotopic liver
      transplantation].
AB  - INTRODUCTION: Pseudoaneurysm of the hepatic artery is a rare complication of
      liver transplantation, the most common cause of which--apart from technical
      surgical problems--is an infection. The most common symptoms are rupture and
      hemorrhage. METHOD: The present case report describes an asymptomatic
      pseudoaneurysm of the hepatic artery following liver transplantation, and its
      treatment. RESULTS: In this patient, an pseudoaneurysm involving an eroded branch
      of the hepatic artery was found. Surgical treatment consisted in the excision of
      the aneurysm and oversewing of the branch of the hepatic artery. CONCLUSION: The
      potential for rupture and hemorrhage makes surgical intervention mandatory even
      in asympotomatic patients with pseudoaneurysm of the hepatic artery. The surgical
      procedure depends on the local situation and the time elapsed since
      transplantation. Preservation or reconstruction of the arterial perfusion is
      essential.

PMID- 11225462
TI  - [Abdominal hemorrhage in multiple intrahepatic aneurysms].
AB  - A 17-year-old male patient presented with diffuse abdominal pain, acute drop in
      hemoglobin and free subhepatic fluid. The patient was transferred to our unit for
      investigation of presumed spontaneous hepatic bleeding. Questioning revealed
      daily medication of 2 g acetylsalicylic acid because of influenzal infection. At
      exploratory laparoscopy 1.8 l hematoma was removed; the origin of bleeding could
      not be identified. The liver surface appeared macroscopically unremarkable, with
      the exception of an aneurysmal dilatation of the cystic artery that was
      considered as possible bleeding cause. Postoperative angiography confirmed the
      presence of multiple aneurysmal dialatations of both left and right hepatic
      arteries. Extensive investigations did not show any further aneurysms or vascular
      abnormalities in any other part of the body. There was no evidence of a
      preexistent systemic vasculitis or primary collagen disease.

PMID- 11225463
TI  - [Pulmonary blastoma--a rare malignant lung tumor].
AB  - Pulmonary blastoma is a rare non-small-cell lung cancer. In a statistically
      significant proportion of cases it is combined with cystic lung disease in
      children. The biphasic pulmonary blastoma and the well-differentiated fetal
      adenocarcinoma are the most frequent manifestations of pulmonary blastoma. If
      metastatic disease is ruled out, surgical therapy should be guided by the
      principles for radical therapy of NSCLC. There are no sufficient recommendations
      yet for therapy of stage IIIb and IV (UICC 1997) disease.

PMID- 11225464
TI  - [Comment on S. Willis et al.: Surgical therapy of high anorectal and rectovaginal
      fistulas with transanal and endorectal advancement flaps].

PMID- 11225465
TI  - [Surgical therapy of nerve tumors].

PMID- 11225466
TI  - [Blood specimen collection in HIV--without patient consent].

PMID- 11225467
TI  - [Myocarditis in childhood: results of a decade's research].
AB  - The research of the last decade gave new insights in the pathogenesis of viral
      myocarditis. The virus infection of the myocardium may be controlled by the
      infiltrating inflammatory cells and heal with more or less scarring. An
      autoimmune mediated chronic inflammation is observed as well as the persistence
      of virus genoms, which causes with low replication rate again chronic
      inflammation. The immunohistochemical characterization of the infiltrating immune
      cells and the molecular biological proof of virus genoms in endomyocardial
      specimens allow a sensitive diagnostic of the various forms of myocarditis and
      should guide therapy. Until now treatment trials did not differentiate between
      these various forms, had no control groups or very small numbers of patients. Two
      multicenter treatment trials in Germany referring to immunosuppressive or
      interferon therapy in children and adults may give--provided a better
      participation--recommendations for therapy.

PMID- 11225468
TI  - [Hyperthyroidism in early childhood and a very rare variant of glutaric aciduria:
      coincidence or causal relation?].
AB  - Hyperthyrosis is a rare disease in early childhood typically characterized by
      tachycardia, restlessness, elevated body temperature, failure to thrive,
      diarrhoea, goiter and a tendency to hyperglycaemia. A 3-year old boy presented
      with typical symptoms of thyrotoxicosis accompanied by ketotic hypoglycemia and
      excessively high glutaric acid excretion. To our knowledge this association has
      so far not been described. Specific defects responsible for glutaric aciduria
      types I & II were excluded. Our patient suffered from glutaric aciduria type III
      which was described once and is characterized by mild metabolic signs.

PMID- 11225469
TI  - [Body complaints and neuroticism in pediatric patients with rheumatism].
AB  - BACKGROUND: Pain and aches are part of subjective experience. Caring for
      chronically ill children and adolescents not only objective results but also the
      children s subjective perception of their illness should be taken into
      consideration. We have tried to record the extent of subjective suffering of a
      group of pediatric rheumatic patients and to correlate our findings with
      personality traits. PATIENTS AND METHOD: We interviewed thirty-one 8 to 18 years
      old children and adolescents (average age 12 years) by means of a standardized
      questionnaire (Giessener Beschwerdefragebogen) and of a standardized personality
      questionnaire (HANES,KJ). The tested group comprised of 9 boys and 22 girls. 14
      patients suffered from a chronic oligoarthritis, 9 from a chronic polyarthritis,
      8 from a other rheumatic disease. Percentiles of more than 89 percent have been
      considered significant compared to norm collectives. RESULTS: 28% of the patients
      showed augmented values on the scales "exhaustion" and "intestinal pain", 25% on
      the scale "pain in joints". Only 3 respectively 2 patients showed augmented
      values on the scales "heart" and "symptoms of cold". 28% showed augmented values
      on the overall scale "feeling of discomfort". 35% showed augmented values on
      neuroticism, 61% values > 89. percentile on the scale "extraversion". There is a
      significant connection between augmented strong feelings of discomfort and
      augmented values of neuroticism on the level 0.1%. A context to the duration of
      the illness was not found. CONCLUSION: Experience of physical pains is not only
      limited to isolated symptoms of the basic illness but also associated with
      general features of personality.

PMID- 11225470
TI  - [Home blood pressure self-measurement in children and adolescents with renal
      replacement therapy].
AB  - BACKGROUND: Most patients with terminal renal failure show arterial hypertension.
      In addition to casual blood pressure measurements in the clinic, home blood
      pressure measurement is recommended for these patients to control arterial blood
      pressure. PATIENTS: The study was performed in children with hemodialysis (HD; n
      = 11), peritoneal dialysis (PD; n = 14) or after renal transplantation (NTX; n =
      21) from one department of Pediatric Nephrology. We performed a retrospective
      analysis of home blood pressure values from patients' diaries. METHODS: The
      average number of blood pressure measurements per day and the mean blood pressure
      values were calculated from the blood pressure data documented during one month
      at home. Single measurements above the 95th percentile for height and gender were
      defined to be hypertensive and the frequency as percentage of all documented
      values was calculated. RESULTS: Four patients did not document any blood pressure
      values at home. The other patients documented an average of 2.3 measurements per
      day. Systolic hypertension was found in 7% of patients defined by home BP
      measurements compared to 30% defined by casual BP measurements. Prevalence of
      diastolic hypertension did not differ between both methods (35% vs. 46%). Mean
      home BP was significantly higher than values after HD and lower than values
      before HD. Mean clinic BP was significantly higher in PD-patients compared to
      home BP. Home and clinic blood pressure values did not differ in patients after
      renal transplantation. The mean percentage of hypertensive readings for systolic
      BP was 5 and for diastolic BP 39%. CONCLUSIONS: Blood pressure measurement at
      home is performed reliably by most children and adolescents with chronic renal
      failure and shows lower values than clinic BP in many patients. It is an
      important method for control of blood pressure and a valuable supplement to 24 h
      blood pressure monitoring.

PMID- 11225471
TI  - [Neonatal ascites: meconium ileus with perforation in mucoviscidosis].
AB  - Many conditions are known associated with neonatal ascites such as cardiac and
      vascular malformations, as well as malformations of the brain, kidney, lung and
      bone, chromosomal abnormalities, infections, fetal anemias, tumors, metabolic and
      maternal conditions. In 30% no reason can be found. Meconium ileus is a causal
      gastrointestinal abnormality. We report about a preterm infant 35 weeks of
      gestation with complicated meconium ileus because of mucoviscidosis.

PMID- 11225472
TI  - [First manifestation of migraine as acute confusional state: "confusional
      migraine" and diagnostic problems].
AB  - We report on a 11-year-old girl with a first migrainous attack presenting as a
      confusional state. The diagnosis was made after the acute episode had subsided.
      Other conditions as encephalitis or space occupying lesions must be ruled out. We
      discuss the diagnostic and therapeutic consequences.

PMID- 11225473
TI  - Pamidronate and calcitonin as therapy of acute cancer-related hypercalcemia in
      children.
AB  - Severe symptomatic hypercalcemia is a rare event in children with malignancies.
      Up to now there is limited experience treating childhood hypercalcemia with
      bisphosphonates in addition to calcitonin. We report a 5-year-old boy with acute
      lymphoblastic lymphoma who presented with malignant hypercalcemia at diagnosis.
      The maximal serum calcium concentration was 15.2 mg/dl (3.81 mmol/l).
      Conventional therapy with forced diuresis and furosemide failed. Calcitonin (10
      IU/kg/24 h i.v. for 2 days) and pamidronate (1 mg/kg over 2 hours i.v.) were used
      successfully without adverse effect lowering the serum calcium level within 24
      hours to normal values. We recommend the use of calcitonin and pamidronate as
      first-line therapy together with forced diuresis and furosemide in childhood
      hypercalcemia secondary to malignancies as it is rapidly effective and has no
      significant side effects.

PMID- 11225474
TI  - [Lactobacillus paracasei endocarditis in an 18-yeard-old patient with trisomy 21,
      atrioventricular septal defect and Eisenmenger complex: therapeutic problems].
AB  - Endocarditis caused by lactobacilli is very rare and so far has been rarely
      published in adults with cardiac valve diseases especially after dental
      manipulations. Because of diagnostic and therapeutical problems we hereby report
      on one case of a female adolescent with Down's syndrome who did not undergo
      surgical correction of atrioventricular septal defect because of early
      development of Eisenmenger's syndrome. The onset was subacut and the diagnostic
      procedures were considerably delayed. Risk factors for the development of
      endocarditis in this case were preceding antibiotic treatments which increased
      the risk of selective growth of the causative germs as well as the tricuspidal
      valve incompetence with simultaneous pulmonary hypertension. The antimicrobial
      treatment was difficult due to resistance to antibiotic drugs generally applied
      in such cases and the restricted bacteriological diagnostic methods. Finally we
      had successfully administered chloramphenicol. The course was complicated by
      cerebral embolic events. FACIT: Lactobacillus species are facultative pathogenic
      which should be consideration in cases of subacute endocarditis in children and
      adolescents with ventricular septal defects and valve diseases. The determination
      of minimal bactericidal concentration of antibiotic agents and time-kill studies
      of combined antibiotics are recommended. For initial therapy we recommend high
      dose penicillin combined with an aminoglycoside. In cases of resistance
      chloramphenicol should be taken into account as second choice antibiotic drug.
      The duration of antibiotic therapy should at least over six weeks. In cases of
      risk systemic embolization is suspected therapy with low dose acetylsalicyclic
      acid or cardiosurgery should be assumed as therapeutic options.

PMID- 11225475
TI  - [Tufted angioma].
AB  - We present a 2-year-old boy with a red, cutaneous-subcutaneous, nodule on the
      right elbow and a 2.5 year-old girl with an red-brown, indurated plaque on the
      left knee. Colour-coded doppler sonography of the boy's lesion showed vascular
      structures. A biopsy established the diagnosis of tufted angioma in both
      patients. Tufted angioma is clinically characterized by slowly spreading
      erythematous macules and plaques preferentially located on the upper trunk and
      neck in children. It is a benign tumor, malignant transformation has not been
      reported. The case history, clinical and histological findings contribute to the
      diagnosis. Tufted angioma has to be distinguished from Kaposi's sarcoma,
      angiosarcoma, hemangioma of infancy, sometimes bacillary angiomatosis and other
      cutaneous capillary malformations. Treatment of tufted angioma is difficult,
      various modalities like glucocorticosteroids, Interferon-alpha, flashlamp-pumped
      pulsed dye laser, excision and spontaneous regression have been described with
      varying results.

PMID- 11225476
TI  - [Bardet-Biedl syndrome: aspects of nephro-urology and human genetics].
AB  - Bardet-Biedl syndrome is a genetically heterogeneous autosomal recessive complex
      of features in which five gene loci have been described up to now. The diagnosis
      of this rare syndrome is based on the main manifestations hypogonadism, age
      dependent increasing obesity and reduction of renal function, age-dependent
      progressive retinal degeneration with blindness as well as postaxial polydactyly
      and mental retardation. The life expectancy is short. Problems of early
      diagnostics, secondary hyperparathyroidism as well as surgical reconstruction of
      the genitals and kidney replacement therapy are discussed.

PMID- 11225477
TI  - [Heparin use in geriatrics and risk profiles of treated patients. A survey in
      France].
AB  - OBJECTIVES: Nursing home residents and geriatric ward patients have a high risk
      of venous thromboembolism. Prevention is a major challenge. We conducted a one
      day audit to ascertain heparin use patterns in a large sample of geriatric
      facilities in France. METHODS: This one-day audit was made with a questionnaire
      mailed to 150 geriatric centers in France. Items were the number of subjects
      receiving heparin on the day of the survey, and for each of these subjects, the
      reason for the prescription, risk factors for venous thromboembolism and date of
      treatment onset. RESULTS: Ninety-six centers (63%) participated. These centers
      had 14,208 beds the day of the survey (short-term hospitalization, day-care
      hospitalization, nursing homes, retirement homes). These centers reported 1,312
      subjects (9.2%) receiving heparin on the day of the survey. Their mean age was
      83.4 days. Among the hospital centers, heparin had been prescribed in 33.4% of
      the short-term hospitalization patients, 27.3% of the day-care patients, and 5.6%
      of the nursing home patients. Heparin was prescribed for prophylaxis in 1,143
      patients (87%)--basically low-molecular-weight heparin. These patients had on the
      average 3.33 risk factors. The duration of preventive treatment was more than 30
      days in 481 subjects (50%) and 161 (17%) had received heparin for 6 months or
      more. CONCLUSION: Prevention of venous thromboembolism is a major concern in
      geriatric centers in France. Although the preventive efficacy has not been
      clearly demonstrated in geriatric medical patients, low-molecular weight heparin
      is widely used for this purpose with, in a large number of cases, very long
      treatment durations.

PMID- 11225478
TI  - [Incidence of symptomatic celiac disease in French children].
AB  - OBJECTIVE: The study was carried out by the GFHGNP to determine the annual
      incidence of symptomatic celiac disease in children. PATIENTS AND METHODS: The
      diagnostic criteria were: symptomatic patients diagnosed under 15 years of age
      during 1996, villous atrophy and positivity of antigliadin and/or other
      antibodies. Cases were collected from referral centers, general hospital
      pediatric departments and private pediatricians with endoscopic practice.
      RESULTS: The study involved roughly half of the French pediatric population in 41
      out of the 95 French districts. In all, 124 patients were collected: 76 girls and
      48 boys. By geographical areas, in 30 districts where collection of data was
      complete which counted 186,285 births, the yearly incidence varied from 1/1731
      births to 1/3110. (0.57@1000 to 0.32@1000). On the whole there were 77 cases i.e.
      an annual incidence of 1/2419 or 0.41@1000 (confidence interval 95%: 0.32 to
      0.50@1000). Lower incidences were observed in the district of Paris: 1/4865
      (0.21@1000) and Lyon: 1/3310 (0.27@1000). Those lower incidences could be
      explained by the difficulties of collecting the data in the biggest urban areas.
      The first signs occurred before one year of age in 73% of the cases, during the
      second year of life in 20.5% and after 3 in only 6.5%. The diagnosis was made
      before 2 years of age in 77% of the cases and after 3 in only 13%. In order of
      frequency symptoms were: failure to thrive (80%), diarrhea (59%), anorexia (59%),
      abdominal distension (57%), weight under 2 standard deviations (43%), short
      stature (43%). CONCLUSION: Compared with previous studies in two French districts
      between 1975 and 1990, the annual incidence of symptomatic celiac disease in
      children appears to be on the rise. The usual clinical signs continue to be
      observed.

PMID- 11225479
TI  - [Acute pulmonary edema caused by tocolytic therapy with salbutamol].
AB  - BACKGROUND: Acute pulmonary edema may be induced by beta 2-mimetics used for
      tocolysis. CASE REPORT: A 41-year-old patient, admitted for preterm labor,
      presented acute pulmonary edema after parenteral tocolysis using salbutamol in
      combination with corticosteroid therapy to improve fetal pulmonary maturation.
      DISCUSSION: The pathogenic mechanism is essentially non-cardiologic. Fluid
      retention is probably the main cause, potentially worsened by corticosteroid
      administration. If detected early, pulmonary edema is usually and adequately
      treated by cessation of beta 2-sympathomimetic therapy, oxygen administration and
      diuretics. Mechanical ventilation can be required. Cardiac function must be
      assessed after this complication. In preterm labor, the duration of tocolysis
      with beta 2-sympatomimetics should be reduced.

PMID- 11225480
TI  - [Kluver-Bucy syndrome in herpetic meningoencephalitis].
AB  - BACKGROUND: Kluver-Bucy syndrome (KBS) is an infrequent condition that includes,
      in its complete form, often massive amnesia, psychic blindness (so-called visual
      agnosia), oral tendencies, hypermetamorphosis, changes in emotional behavior and
      increased sexual activity. Anatomic lesions in KBS involve the temporal lobe
      cortex bilaterally, and the amygdala as well as temporal white matter. CASE
      REPORT: A 17-year-old patient treated for herpetic meningoencephalitis developed
      neuropsychological signs leading to the diagnosis of Kluver-Bucy syndrome.
      DISCUSSION: KBS can occur in various clinical conditions but herpetic
      encephalitis is the most frequent cause. KBS may be transient or partially
      regressive, but severe amnesia that may progress to Korsakoff syndrome is often
      persistent after herpetic encephalitis. Neuroleptics or carbamazepine can be used
      for symptomatic treatment.

PMID- 11225481
TI  - [Cardiorespiratory arrest at a ski station in the Pyrenees: analysis of
      prognostic factors].

PMID- 11225482
TI  - [The elderly: management of falls in general medicine].

PMID- 11225483
TI  - [Regressive posterior leukoencephalopathy revealing systemic arterial
      hypertension].

PMID- 11225484
TI  - [The risks of unrestricted application of the principle of precaution in
      medicine. The need to keep in mind the findings of medical ethics in the
      development of health care rights].
AB  - The principle of precaution, a fundamental, essentially legalistic, rule
      underpinning health care legislation in France, basically arose from
      environmental protection policies. This principle became the topic of a good deal
      of well-publicized debate following the decree concerning HIV contamination
      rendered in 1993 by the Conseil d'Etat, the supreme jurisdiction on legislative
      matters in France. This translation of a fundamental principle from one domain to
      another is not devoid of significance and could have an unexpected impact on the
      nature and meaning of health care itself. When applied to medicine, the principle
      of precaution must be confronted with the notion of risk, inherent in all acts of
      health care. This risk certainly implies patients' rights and informed consent to
      medical care, but also, in a reasonable search for an acceptable balance between
      risk and benefit, the freedom of biomedical research from overly-restrictive
      regulations. Consequently, in accordance with an ethical approach to medical
      care, legislative and judicial bodies must take into consideration the practical
      reality of medicine in order to integrate the scientific, economic, social, and
      psychological aspects of everyday medical practice into health care laws and
      regulations. Once faced with the reality of health care, the principle of
      precaution could appear contradictory to the fundamental principles of medicine.
      Indeed, every physician, every health care worker, makes daily evidence-based
      decisions that are never devoid of risk. Unrestricted application of the
      principle of precaution to a growing number of public domains, including
      medicine, as advocated by a large number of opinion leaders, could lead to an
      inextricable situation, in total contradiction with the goal of health care
      itself. In order to develop new truly ethical and adapted health care
      regulations, we must break down the barriers confining judges and legal
      representatives to a purely legalistic vision of health care and equally
      confining physicians to a purely scientific vision of their mission.

PMID- 11225485
TI  - [Jean-Claude Savoie].

PMID- 11225486
TI  - [Treatment of chronic viral hepatitis B with lamivudine].
AB  - INTERFERON ALPHA AND LAMIVUDINE: Chronic hepatitis B is currently treated with
      interferon alpha and lamivudine. Lamivudine (marketed under the name Zeffix in
      France) is given in oral preparations and is excreted in the urine. It is rapidly
      effective against virus replication since, after a one-month treatment, hepatitis
      B DNA levels are negative in most of the treated patients. After 12 months, there
      is an improvement in liver histology. ADVANTAGES AND DISADVANTAGES: The
      probability of effective treatment is greatest for patients with highly elevated
      transaminase levels and low hepatitis B DNA levels prior to treatment. Another
      advantage of lamivudine is the extremely low rate of side effects. The risk of a
      rebound in viral replication after withdrawal is a drawback together with the
      possible development of viral mutations of the polymerase gene, particularly
      after more than one year of treatment. INDICATIONS: Lamivudine can be prescribed
      for patients with a contraindication or non-responsive to alpha interferon: liver
      transplantation candidates, organ graft recipients. For other cases, alpha
      interferon is the first line treatment of choice. If lamivudine is used too
      early, there is a risk the patients could no longer be transplanted after the
      development of mutations and major aggravation of liver function. Future
      perspectives include simultaneous or sequential use of antiviral agents.

PMID- 11225487
TI  - [Forms of polyarthritis in idiopathic juvenile arthritis].
AB  - DEFINITION: Idiopathic juvenile polyarthritis includes a group of inflammatory
      diseases that affect at least five joints, either from onset or within the first
      six months of the disease course in children under 16 years of age. Diagnosis is
      arrived at by elimination. Besides malignant disease, always to be considered as
      a differential diagnosis, idiopathic juvenile polyarthritis can be divided into
      rheumatoid factor (RF)-positive and RF-negative polyarthritis and extended forms
      of oligoarthritis. RF-NEGATIVE POLYARTHRITIS: Antinuclear antibody (ANA)-positive
      polyarthritis must be distinguished from extended forms of oligoarthritis which
      are also ANA-positive. ANA-positive polyarthritis generally begins early, at the
      age of 2 or 3 years, predominantly in girls. Characteristic torpid uveitis is
      frequent, requiring regular systematic screening. Joints are minimally painful
      with symmetrical involvement, usually of the knees and wrists. Progressive joint
      destruction and/or growth disorders are common. The disease progresses by acute
      episodes. Nonsteroidal antiinflammatory drugs are used, associated with a
      specific treatment and local care as needed. General corticosteroids may be
      required in certain cases but should be avoided if possible. SERONEGATIVE FORMS:
      Certain patients have no detectable antibodies. These patients generally have
      fewer ocular problems and less severe joint disease. The treatment is the same as
      in ANA-positive forms. RF-positive polyarthritis: RF-positive polyarthritis is
      exceptional and occurs early in young girls. SPECIALIZED CARE: Irrespective of
      the type of disease, all children with idiopathic juvenile polyarthritis require
      multidisciplinary specialized care for their chronic and severe, potentially
      invalidating disease.

PMID- 11225488
TI  - [Microsporidiosis].
AB  - OPPORTUNISTIC PARASITES: Microsporidia are primitive eukaryotic parasites
      widespread in a large range of animal species. These opportunistic parasites can
      cause infections in humans, mainly in immunocompromised patients. PATHOGENIC
      SPECIES: Four microsporidian species are important in human pathology,
      Enterocytozoon bieneusi, Encephalitozoon intestinalis, Encephalitozoon cuniculi
      and Encephalitozoon hellem. LABORATORY DIAGNOSIS: A difficult task, laboratory
      diagnosis is based on direct microscope visualization of the parasite. Special
      stains not used in routine practice are required for identifying spores.
      TREATMENT: Species differentiation, achieved with the polymerase chain reaction
      technique, is necessary to select the appropriate treatment. Treatment of the
      most common microsporidiosis (caused by Enterocytozoon bieneusi) with fumagillin
      is currently under assessment in an ANRS clinical trial.

PMID- 11225489
TI  - [Zollinger-Ellison syndrome, morphologic features in digestive echoendoscopy].

PMID- 11225490
TI  - [Quintuple mitral valve insufficiency].

PMID- 11225491
TI  - [Diagnosis o Yersinia enterocolitica infections: a review on classical
      identification techniques and new molecular biological methods].
AB  - Only three of the eleven species of the genus Yersinia are associated with
      disease. Y. pestis is the causative agent of plague, Y. pseudotuberculosis and
      several pathogenic bio/serovars of the species Y. enterocolitica cause
      yersiniosis. New Y. enterocolitica subspecies with diagnostic relevance have been
      proposed allowing the differentiation of European and American isolates. The ISO
      standard (ISO 102739) summarizes the knowledge gained from enrichment and
      isolation of Y. enterocolitica from food and feed samples. The final biochemical
      identification must be carried out by classical tube testing, as commercially
      available test-systems are not sensitive and specific. For the assessment of the
      presumptive pathogenicity of a Y. enterocolitica isolate empiric virulence
      markers can be replaced by PCR assays targeting plasmoidal or chromosomal genes.
      Their evaluation in terms of routine diagnostic procedures is still missing. The
      definite identification of Y. enterocolitica isolates can also be achieved by
      sequencing the 16S rRNA gene. Immunoblot based on plasmoidal encoded Yersinia
      proteins enables the serological determination of animal and human infections.
      The development of simple, sensitive and specific rapid identification systems
      applicable for the direct and indirect diagnosis for veterinary use is a
      challenge for the future.

PMID- 11225492
TI  - [Bovine sole ulcer: a literature review].
AB  - Sole ulcers are the most frequently encountered lesion in lame cattle. They are
      of growing concern to the dairy industry since the incidence of ulcers is
      increasing. Ulcers cause financial losses, the animal's wellbeing is disturbed to
      a high degree and they harm the image of the industry in general. Biomechanic
      factors and laminitis are of particular significance in the pathogenesis of the
      sole ulcer. The development of sole contusions and ulcers is assumed to occur in
      3 phases (Sinking theory). In the first phase there is a general disturbance in
      the vascular system of the corium. The second phase follows when the structures
      that suspend the claw bone within the horn shoe give way. The locus minoris
      resistentiae has yet to be identified. The claw bone sinks and causes various
      lesions when it pinches the underlying sole or heel corium. The third phase
      begins when haemorrhages become visible on the horn surface of the sole or when
      the sole ulcerates; socalled third phase lesions. The relationship between the
      development of sole ulcers and anatomical structures such as the claw bone's
      tuberculum flexorium or the fat bodies under the bone are unclear.
      Epidemiological studies have shown that sole ulcers have a high rate of
      recurrence. The healing processes and the factors that influence them have
      hitherto not been studied.

PMID- 11225493
TI  - [Occurrence and economic importance of congenital hernia in German Fleckvich
      calves].
AB  - The frequency of congenital hernia was investigated in German Fleckvieh calves
      being driven up for sale on livestock markets for breeding and fattening calves
      in Miesbach and Traunstein. Data were collected on 77 livestock auctions in the
      years 1996 and 1997. Altogether 53,105 calves were examined and 1.8% of these
      calves showed a congenital umbilical hernia. The incidence of umbilical hernia
      was significantly influenced by the sex of the calf, the occurrence of multiple
      births, the market place/market date, the sire and the sire line. Red Holstein
      blood proportion, lactation number, duration of pregnancy and 305 day milk
      performance were not of significant importance. Herd milk level did not influence
      the incidence of congenital umbilical hernia, however, herdmate averages for
      calves differed significantly in their incidence. The average difference of the
      market price between male calves affected by congenital umbilical hernia and not
      affected male calves amounted to 75 DM, in female calves, however, only to 38 DM.
      The risk, that a congenital umbilical hernia is not closing within an age of 15
      months, depends on the width of the hernial opening in the newborn calf. An
      opening of 4 cm and more has only a healing chance of 50% and less. However,
      negative effects on fattening and carcass traits could be not found. The genetic
      influence on congenital umbilical hernia was obvious. The analyses indicated that
      the incidence of congenital umbilical hernia observed could not be explained by
      one autosomal recessive gene locus, but it seemed much more likely that more than
      one gene locus is involved or a mixed multifactorial monogenic mode of
      inheritance may be the underlying genetic mechanism. Breeders should be aware of
      the implications of congenital hernias and thus, congenital hernia should get
      more attention in the selection process of young sires.

PMID- 11225494
TI  - [Sampling plan for the establishment of a serologic Salmonella surveillance for
      slaughter pigs with meat juice ELISA].
AB  - The guidelines of the German Ministery of Food, Agriculture and Forestry
      outlining a Salmonella surveillance programme, "Leitlinien fur ein Programm zur
      Reduzierung des Eintrags von Salmonellen durch Schlachtschweine in die
      Fleischgewinnung" (February 5th, 1998), provide a staggered spot-check size
      depending on the annual production of slaughtery pigs. A classification of farms
      into three quality categories (< 20%, 20-40%, and > 40%) is performed by
      salmonella antibody levels detected in meat samples using ELISA. Beside a
      fundamental inquiry into the salmonella status, the programme ought to lead to a
      decreased burden on slaughtery pigs and finally to a reduced salmonella entry
      into meat handling and processing companies. The spot-check plan is based on an
      unfavourable initial position and does not consider the real situation of
      salmonella load in pig fattening farms. For many farms the procedure will lead to
      an unjustified expenditure of examinations. In simple model calculations it is
      shown how a significant reduction of testing amount can be reached and
      statistical reliability is guaranteed, too. At the same time, we attempt to find
      a compromise between optimal spot check size and practicability. For reasons of
      free enterprise, an additional category would be desirable containing farms
      without any positive antibody titres in the samples. The results achieved so far
      indicate that a large number of German slaughter pig producers would fall into
      this category, without the necessity of a higher examination effort.

PMID- 11225495
TI  - [Meat juice ELISA for determination of Salmonella incidence in slaughter pig
      herds in Bavaria].
AB  - Meat samples from diaphragm pillars were randomly taken from 3,048 pigs of 52
      Bavarian herds after slaughtery. Meat-juice was collected and tested for
      salmonella antibodies in an indirect ELISA. The number of samples was calculated
      according to the annual production of slaughter pigs of a farm outlined in the
      "Leitlinien fur ein Programm zur Reduzierung des Eintrags von Salmonellen durch
      Schlachtschweine in die Fleischgewinnung" from February 05th, 1998 (< 100
      slaughter pigs: 45 samples, 100-200 slaughter pigs: 50 samples, > 200 slaughter
      pigs: 60 samples per year). Salmonella antibodies were detected in 48 carcasses
      (1.6%) of 12 farms (23.1%). However, 33 (68.8%) of these carcasses were
      originated from a single farm which had to be classified into category III
      (prevalence of > 40% in the samples). No bacteria could be isolated from this
      farm in a follow up examination. The 51 other farms (98%) were classified into
      category I (prevalence of < 20% in the samples). Farms with in/out-management
      showed a higher degree of reagents (2.1T%) than farms with continuous stabling
      (0.8T%). In a pig experimentally immunized with LPS-antigen preparations of
      Salmonella typhimurium it was shown that antibodies induced were nearly at the
      same level in all meat samples and even in selected organs (liver, kidney,
      parotis, mesenteric lymph nodes).

PMID- 11225496
TI  - [Case report: (erythro)keratoderma variabilis in a newborn foal].
AB  - A case of congenital (Erythro)keratoderma variabilis in a newborn foal is
      described. The clinical and histological findings are presented.

PMID- 11225497
TI  - [Temporal skin plastic surgery, a possible method for eyelid reconstruction].
AB  - Eyelid reconstruction of large defects is a difficult undertaking in small animal
      surgery. Instead of performing the well known Roberts and Bistner or Cuttler and
      Beard methods, we have introduced the following method for eyelid correction in
      case of large lid defects. On the temporal part, laterally (about the width of
      the eye) from the eye an uneffected skin flap is identified, mobilized, rotated
      and placed into the missing part of the eyelid. Conjunctiva (with slow resorbing)
      and skin (with non resorbing) 1 metric material are separately adapted. In a
      large number of patients this method has been proven to be superior to the other
      methods mentioned.

PMID- 11225498
TI  - [Determination of heart dimensions in cattle via 2-D-mode echocardiography].
AB  - The goal of this study was to determine via echocardiography the size of the left
      and right cardiac ventricles and the width of the interventricular septum and the
      left free ventricular wall in 51 healthy cows. The heart regions were examined in
      standing cows using a 3.0 Mhz sector transducer in 2-D-Mode. The dimensions of
      the heart were measured in the caudal long and short axes on the right side and
      in the caudal and cranial long axes on the left. The diameter of the ventricles
      was determined in a plane immediately beneath the mitral or tricuspid valves and
      that of the aorta and pulmonary artery in a plane immediately above the aortic
      and pulmonary valves, respectively. At the end of the study, all of the cows were
      slaughtered, the hearts were removed and the same parameters were determined
      using a tape measure. Results of in vivo and in vitro measurements were compared.
      In the right caudal long axis, the diameters of the left ventricle during both
      diastole (x +/- s = 7.0 +/- 0.73 cm) and systole (4.5 +/- 0.69 cm) were larger
      than those of the right ventricle during diastole (4.1 +/- 1.02 cm) and systole
      (3.6 +/- 0.98 cm). The diameter of the ventricles during diastole was larger than
      that during systole. Analogous results were obtained in both other axes. The
      diameter of the right ventricle during systole was larger when measured in the
      right caudal long axis (3.6 +/- 0.98 cm) than in the right caudal short axis (3.2
      +/- 1.15 cm). This was also true for measurements obtained during diastole. The
      interventricular septum and the left ventricular wall were thicker during systole
      than during diastole. The diameter of the pulmonary artery was larger during
      diastole (5.6 +/- 0.82 cm) than systole (5.2 +/- 0.84 cm). The diameter of the
      aorta was smaller than that of the pulmonary artery and did not change
      significantly during diastole (4.9 +/- 0.92 cm) and systole (4.8 +/- 0.80 cm).
      The diameters of both ventricles measured at post mortem were smaller than those
      measured in vivo during diastole and larger than those measured during systole.
      There were no significant differences between the measurements performed twice,
      three days apart, in 11 of the cows.

PMID- 11225499
TI  - [Investigations on the usefulness of the dry chemistry blood anaylsis system
      SPOTCHEM SP-4410in laboratory diagnosis of cattle].
AB  - The usefulness of the dry-chemistry blood analyzer, SPOTCHEM SP-4410, for
      analysis of bovine blood chemistry was studied in a veterinary clinic. The
      control serum Precipath-U, Boehringer-Mannheim, was used to measure precision
      within each run and between days. The coefficients of variation (CV) ranged
      between 1.54% and 4.86%, with the exception of albumin and creatine phosphokinase
      showing a CV of 6.3% and 10.03% for between-day precision. For methodological
      comparison bovine serum samples were assayed with both the SPOTCHEM SP-4410 and
      the automated blood analyzer HITACHI 705, which served as a wet-chemistry
      reference system. The following analytes were measured: glucose, urea,
      creatinine, total protein, albumin, total bilirubin and the enzymes AST, CPK and
      gamma-GT. For hemoglobin, which was measured in heparinized whole blood, the CO
      oximeter 855, CIBA-CORNING, was used as a reference system. The comparative
      analysis showed very good correlation in eight of ten parameters and their
      correlation coefficients (r) ranged between 0.962 and 0.998. Only the correlation
      coefficients of the analysis of total bilirubin (r = 0.903) and albumin (r =
      0.771) were less satisfactory. The recovery test was carried out with the two
      parameters glucose and blood urea. The recovery of glucose was 93.7% and of urea
      98.8%. The SPOTCHEM SP-4410 is easy to use and proved to be reliable and
      accurate, and therefore it seems to be useful for analysis of bovine blood
      samples.

PMID- 11225500
TI  - [Pharmacokinetics of kanamycin after subcutaneous and intravenous administration
      in dogs].
AB  - Six beagle dogs were treated with kanamycin subcutaneously or intravenously in a
      dosage of 5 mg/kg. The plasma kanamycin concentration was measured over 24 hours
      by high pressure liquid chromatography with UV detection after derivatization and
      solid phase extraction. After subcutaneous application, kanamycin was absorbed
      quickly, and maximum plasma levels of 18.9 micrograms/ml in average after ca. 1
      hour were measured. With complete systemic availability, the minimal inhibitory
      concentration of 4 micrograms/ml was maintained for 4 hours. After subcutaneous
      administration, kanamycin was terminally eliminated with a mean half life period
      of 2 hours.

PMID- 11225501
TI  - [Yersinia enterocolitica infections: 1. Impact on animal health].
AB  - In Europe, yersiniosis is mainly caused by the bacterial species Yersinia
      enterocolitica. The clinical picture of yersiniosis in farm animals including
      pig, chinchilla, cattle, small ruminants and the pet animals dog and cat is
      described in detail. However, data on seroprevalence and prevalence in these
      animals are not available. Therefore, further research is needed in the fields of
      epidemiology and epizootiology.

PMID- 11225502
TI  - Overview and clinical presentation of generalized anxiety disorder.
AB  - 1. To distinguish GAD from panic disorder is not difficult if a patient has
      frequent, spontaneous panic attacks and agoraphobic symptoms, but many patients
      with GAD have occasional anxiety attacks or panic attacks. Such patients should
      be considered as having GAD. An even closer overlap probably exists between GAD
      and social phobia. Patients with clear-cut phobic avoidant behavior may be
      distinguished easily from patients with GAD, but patients with social anxiety
      without clear-cut phobic avoidant behavior may overlap with patients with GAD and
      possibly should be diagnosed as having GAD and not social phobia. The cardinal
      symptoms of GAD commonly overlap with those of social phobia, particularly if the
      social phobia is more general and not focused on a phobic situation. For example,
      free-floating anxiety may cause the hands to perspire and may cause a person to
      be shy in dealing with people in public, and thus many patients with subthreshold
      social phobic symptoms have, in the authors' opinion, GAD and not generalized
      social phobia. The distinction between GAD and obsessive-compulsive disorder,
      acute stress disorder, and posttraumatic stress disorder should not be difficult
      by definition. At times, however, it may be difficult to distinguish between
      adjustment disorder with anxious mood from GAD or anxiety not otherwise
      specified, particularly if the adjustment disorder occurs in a patient with a
      high level of neuroticism or trait anxiety or type C personality disorder. Table
      2 presents features distinguishing GAD from other psychiatric disorders. 2.
      Lifetime comorbid diagnoses of other anxiety or depression disorders, not active
      for 1 year or more and not necessitating treatment during that time period,
      should not effect a diagnosis of current GAD. On the other hand, if concomitant
      depressive symptoms are present and if these are subthreshold, a diagnosis of GAD
      should be made, and if these are full threshold, a diagnosis of MDD should be
      made. 3. If GAD is primary and if no such current comorbid diagnosis, such as
      other anxiety disorders or MDD, is present, except for minor depression and
      dysthymia, or if only subthreshold symptoms of other anxiety disorders are
      present, GAD should be considered primary and treated as GAD; however, patients
      with concurrent threshold anxiety or mood disorders should be diagnosed according
      to the definitions of these disorders in the DSM-IV and ICD-10 and treated as
      such. 4. Somatization disorders are now classified separately from anxiety
      disorders. Some of these, particularly undifferentiated somatization disorder,
      may overlap with GAD and be diagnostically difficult to distinguish. The authors
      believe that, as long as psychic symptoms of anxiety are present and predominant,
      patients should be given a primary diagnosis of GAD. 5. Two major shifts in the
      DSM diagnostic criteria for GAD have markedly redefined the definition of this
      disorder. One shift involves the duration criterion from 1 to 6 months, and the
      other, the increased emphasis on worry and secondary psychic [table: see text]
      symptoms accompanied by the elimination of most somatic symptoms. This decision
      has had the consequence of orphaning a large population of patients suffering
      from GAD that is more transient and somatic in its focus and who typically
      present not to psychiatrists but to primary care physicians. Therefore,
      clinicians should consider using the ICD-10 qualification of illness duration of
      "several months" to replace the more rigid DSM-IV criterion of 6 months and to
      move away from the DSM-IV focus on excessive worry as the cardinal symptom of
      anxiety and demote it to only another important anxiety symptom, similar to free
      floating anxiety. One also might consider supplementing this ICD-10 criterion
      with an increased symptom severity criterion as, for example, a Hamilton Anxiety
      Scale of 18. Finally, the adjective excessive, not used in the definition of
      other primary diagnostic criteria, such as depressed mood for MDD, should be
      omitted (Table 3). 6. One may want to consider the distinction of trait (chronic)
      from state (acute) anxiety, but whether the presence of some personality
      characteristics, particularly anxious personality or Cluster C personality and
      increased neuroticism, as an indicator of trait [table: see text] anxiety is a
      prerequisite for anxiety disorders; occurs independently of anxiety disorders; or
      is a vulnerability factor that, in some patients, leads to anxiety symptoms and,
      in others, does not, is unknown. 7. Symptoms that some clinicians consider
      cardinal for a diagnosis of GAD, such as extreme worry, obsessive rumination, and
      somatization, also are present in other disorders, such as MDD. (ABSTRACT
      TRUNCATED)

PMID- 11225503
TI  - Pharmacologic treatment of generalized anxiety disorder.
AB  - GAD is a severe, chronic, and distressing illness that often requires long-term
      management. Considerable progress has been made in the ability to help these
      patients. New antidepressants, such as venlafaxine, and the SSRIs provide an
      important treatment alternative to "traditional" anxiollytic treatments, which
      include the benzodiazepines, buspirone, and the TCAs; however, comparative
      efficacy and the effects of psychiatric comorbidity, long-term treatment, and
      relapse prevention are areas requiring further investigation.

PMID- 11225504
TI  - Generalized anxiety disorder in children and adolescents.
AB  - Children and adolescents with GAD suffer from excessive, pervasive worries that
      interfere with social, academic, and family functioning. The comorbidity rate
      with other anxiety disorders and major depression is high. The course tends to be
      chronic, and evidence shows continuity between anxiety disorders in youth and
      adulthood. Individual and group CBT and the incorporation of family anxiety
      management training have demonstrated efficacy in the treatment of childhood GAD.
      No double-blind, placebo-controlled, pharmacotherapy trials with adequate sample
      sizes for children and adolescents with GAD have been published. Preliminary data
      support the potential efficacy of selective serotonin reuptake inhibitors,
      buspirone, and high-potency benzodiazepines. Adequately powered, controlled,
      pharmacologic treatment trials are necessary. Future research should be directed
      toward comparing the relative efficacy of psychotherapy, pharmacotherapy, and
      both in the treatment of GAD in youth.

PMID- 11225505
TI  - Generalized anxiety disorder in the elderly.
AB  - Anxiety disorders, especially GAD, are among the most prevalent psychiatric
      illnesses in the elderly. Unfortunately, research relative to late-onset anxiety
      syndromes and longitudinal studies of early-onset anxiety syndromes are sparse.
      Nonetheless, clinicians can properly assess and treat older adults with anxiety
      disorders and improve their quality of life. Additional research is needed to
      better elucidate the various presentations of GAD in the elderly and in
      developing safe, effective, nonpharmacologic and pharmacologic treatment
      approaches.

PMID- 11225506
TI  - Generalized anxiety disorder in women.
AB  - Women have a higher prevalence of GAD than do men. This ratio holds true in most
      clinical and general-population samples. Some variations exist, with evidence to
      suggest the strong impact of environment and life events. Women are sensitive to
      lifetime adversity and exacerbation of symptoms in conjunction with their
      menstrual cycle. Comorbidity is a crucial diagnostic factor when treating anyone
      with GAD, especially women. Most notably, high comorbidity with other anxiety
      disorders, MDD and alcohol-abuse disorder occurs for women. Overall, although the
      prevalence of women with GAD is greater than that of men with GAD, the course of
      illness and prognosis are not qualitatively different. Across varied methodology,
      data suggest gender-related differences in the metabolism and potentially in the
      effects and side effects of the various benzodiazepines and antidepressant
      psychopharmacologic treatments of GAD. Additional research is needed to better
      understand these differences.

PMID- 11225507
TI  - The epidemiology of generalized anxiety disorder.
AB  - The literature reviewed here is consistent in showing that GAD is a common mental
      disorder that typically has an early age of onset, a chronic course, and a high
      degree of comorbidity with other anxiety and mood disorders. Comorbid GAD is
      often temporally primary, especially in relation to mood disorders, and is
      associated with an increased risk for the subsequent onset and severity of
      secondary disorders. The weight of evidence reviewed here argues against the view
      expressed by early commentators that GAD is better conceptualized as a prodrome,
      residual, or severity marker of other disorders than as an independent disorder.
      Focused studies of comorbidity between GAD and major depression, in which
      comorbidity is high, lead to the same conclusion. The crucial evidence for this
      conclusion includes the following: 1. Contrary to the findings of clinical
      studies, GAD in the community does not have a higher comorbidity than do most
      other anxiety or mood disorders. 2. The symptoms of GAD form an empiric cluster
      distinct from the symptoms of major depression in studies of symptom profiles. 3.
      Family studies show distinct aggregation of GAD and major depression. 4. Twin
      studies show that the environmental determinants of GAD are different from the
      environmental determinants of major depression. 5. The sociodemographic
      predictors of GAD in epidemiologic studies are different from the predictors of
      major depression. 6. The clinical course of GAD is less consistently related to
      comorbidity than is the course of other anxiety and mood disorders. 7. The
      impairments associated with GAD are equivalent to, or greater than, those
      associated with other severely impairing chronic physical and mental disorders.
      These findings show that the status of GAD as an independent disorder is at least
      as strongly supported by available evidence as is that of other anxiety or mood
      disorders. This article also shows that uncertainty remains regarding even the
      basic epidemiologic characteristics of the GAD syndrome. Lingering concerns about
      the independence of GAD have conspired to exacerbate this problem by promoting
      repeated changes in the diagnostic criteria for GAD from the DSM-III to DSM-III-R
      and to DSM-IV. These successive changes have made it difficult to amass
      consistent long-term data on the natural history of GAD. Available evidence on
      the empiric validity of current diagnostic thresholds for GAD raises questions
      about the requirements, such as whether a 6-month minimum duration and four or
      more additional psychophysiologic symptoms are optimal for identifying all of the
      people in the general population who suffer from a clinically significant GAD
      syndrome. An additional source of potential bias in this regard is that the DSM
      system requires that anxiety be excessive or unrealistic for a diagnosis of GAD.
      Interestingly, there is no comparable DSM requirement that dysphoria must be
      excessive or unrealistic to qualify as major depression. These diagnostic
      uncertainties make it difficult to gain a clear understanding of the true breadth
      and depth of the GAD syndrome in the general population. Additional research is
      needed, ideally from unbiased epidemiologic samples, to resolve these basic
      uncertainties. The strong comorbidity between GAD and major depression, the fact
      that most people with this type of comorbidity report that the onset of GAD
      occurred before the onset of depression, and the fact that temporally primary GAD
      significantly predicts the subsequent onset of depression and other secondary
      disorders raise the question of whether early intervention and treatment of
      primary GAD would effectively prevent the subsequent first onset of secondary
      anxiety and depression. Unfortunately, little is known about this possibility
      because, as mentioned earlier, few people with pure GAD seek treatment. Why this
      is true is unknown. Given the early onset of GAD and its strong effects in
      predicting the subsequent onset, severity, and persistence of other disorders,
      efforts are needed to collect epidemiologic data on the reasons for the low rate
      of help seeking among people with pure GAD and to develop outreach strategies
      that may correct this situation.

PMID- 11225508
TI  - Comorbidity in generalized anxiety disorder.
AB  - GAD has rates of comorbidity that equal or exceed those of other anxiety
      disorders, and it is one of the most common comorbid conditions with other
      disorders. Depressive disorders, especially MDD, and other anxiety disorders,
      especially panic disorder, most commonly co-occur. The pattern of comorbidity is
      consistent in community and clinical populations and in children and elderly
      people. Comorbidity is associated with greater impairment, more treatment
      seeking, and worse outcome among persons with GAD compared with pure GAD.
      Likewise, patients with panic disorder and MDD who have coexisting GAD tend to
      have more severe symptoms and less favorable outcome. The relationship between
      GAD and MDD seems especially close, and data from twin studies suggest that these
      conditions share a genetic diathesis. Patients with GAD and coexisting conditions
      respond less well to psychological and pharmacologic treatment, but, for those
      who do respond, treatment for the primary disorder often also produces
      improvement in comorbid conditions. Thus, research continues to show that GAD is
      important as a primary and a comorbid disturbance.

PMID- 11225509
TI  - Cognitive theories of generalized anxiety disorder.
AB  - The hallmark feature of generalized anxiety disorder, worry, has been
      hypothesized to be a key factor in the production of threat-related information
      processing biases in the domains of attention, memory, interpretation of
      ambiguity, and problem solving; however, worry and cognitive biases are not
      unique to generalized anxiety disorder. What may be unique to generalized anxiety
      disorder is the pervasive use of worry as a strategy to avoid intense negative
      effect and the broad domains in which these biases are exhibited, directly
      relating to the clinical observation that patients with generalized anxiety
      disorder worry about numerous life stressors. Also, the authors conclude that
      information-processing biases contribute to worry but that they are insufficient
      for the development of generalized anxiety disorder. Directions for future
      research and clinical implications are discussed.

PMID- 11225510
TI  - Neurobiology of generalized anxiety disorder.
AB  - On reviewing the literature on GAD and trying to summarize the various
      developments in the field of neurobiology of GAD, we see that a range of
      hypotheses try to explore and integrate the observations found into potentially
      meaningful theories. Abnormal serotonergic and GABAergic function occur in many
      patients with GAD. Functional imaging data have shown increased cortical activity
      and decreased basal ganglia activity in patients with GAD, which reverses with
      treatment, but it is apparent that no one theory is sufficiently comprehensive to
      propose a unitary hypothesis for the development of GAD and other anxiety
      disorders. GAD is a relatively new diagnosable condition, first introduced into
      the classification system of psychiatric disorders in 1980, and since then has
      undergone a series of changes in its conceptualization, with some investigators
      questioning the existence of the condition as a distinct entity. Any inferences
      that may be drawn from various studies must be guarded, and it is appropriate to
      compare studies using the same diagnostic criteria. Significant research has been
      done and may lead to exciting new discoveries in the treatment of anxiety
      disorders in general and GAD in particular. Gray's model of behavioral
      inhibition, in which the septohippocampal system acts by assessing stimuli for
      the presence of danger and, when that is detected, activates the behavioral
      inhibition circuit, provides a neuroanatomic conceptualization that has been
      expanded by preclinical research. Some exciting work has been done on CRF and the
      concept of development, vulnerability, and kindling and some investigators have
      contributed to this area of interest. This concept supports the hypothesis that a
      genetic predisposition, coupled with early stress, in the crucial phases of
      development may result in a phenotype that is neurobiologically vulnerable to
      stress and may lower an individual's threshold for developing anxiety or
      depression on additional stress exposure. The pharmaceutical industry is
      exploring treatment options using CRF antagonists, and research on other
      neuropeptides, especially NPY, will be of interest. Research on neurosteroids
      also may bring the opportunity for pharmacologic treatment approaches. Future
      research on the startle reflex and on the NMDA and the metabotropic glutamate
      receptors is important. Future studies of a more homogenous patient population
      and using more sophisticated techniques, such as molecular genetic strategies and
      better imaging techniques, may answer some of the outstanding questions.

PMID- 11225511
TI  - The nonpharmacologic treatment of generalized anxiety disorder.
AB  - This article describes the latest nonpharmacologic therapies for generalized
      anxiety disorder. In addition, a review of available nonpharmacologic treatment
      outcome studies and studies that compare the efficacy of pharmacologic and
      nonpharmacologic treatment is presented. The authors conclude that, of the
      nonpharmacologic therapies available, cognitive-behavioral therapy may be the
      preferred first-line treatment. Results of comparison studies have suggested that
      medication acts more quickly than does therapy in reducing symptoms, whereas
      therapy has more long-lasting effects. The authors recommend that further
      research be conducted in identifying the essential components of treatment and
      the most efficacious treatment combinations.

PMID- 11225512
TI  - The effect of ethanol consumption on the sensitivity of rat brain monoamine
      oxidases to the inhibition by pargyline in vivo and in vitro.
AB  - The effect of ethanol consumption on the sensitivity of rat brain mitochondrial
      monoamine oxidases to the inhibition by pargyline in vivo and in vitro was
      investigated. Administration of pargyline (10 mg/kg, s.c.) produced significantly
      higher inhibition of MAO-A in alcoholised rats, whereas MAO-B inhibition did not
      differ from that observed in control animals. The concentration-response curve
      for the inhibition of brain mitochondrial MAO-A and MAO-B by pargyline in vitro
      did not reveal higher sensitivity of MAO from alcoholised rats to pargyline. This
      probably means that more pronounced inhibition by pargyline of brain MAO-A in
      alcoholised rats in vivo can be attributed to decreased content of compounds
      reversibly interacting with the its catalytic site. Taking into consideration
      some ethanol-induced decrease of brain tribulin content we suggest that the
      reduced level of endogenous inhibitors (tribulin components?) may have some
      importance in the development of alcoholism.

PMID- 11225513
TI  - Neuroprotective aspects of a novel MAO-B inhibitor PF9601N.
AB  - PF9601N is an acetylenic tryptamine derivative devoid of amphetamine-like
      properties, that behaves as suicide MAO-B inhibitor more potent than l-deprenyl.
      It is highly selective towards MAO-B and it neuroprotects from the neurotoxicity
      induced in C57Bl/6 adult mice by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP). PF9601N also shows in vitro antioxidant properties by inhibiting the
      dopamine autoxidation. A potential therapeutic use in Parkinson's disease
      treatment is proposed for this compound.

PMID- 11225514
TI  - Involvement of Ca2+ in dopamine release in striatal rat slices by PF9601N and L
      deprenyl.
AB  - Rat striatal slices were incubated 1 hour in Krebs buffer with carbogen by
      continuous perfusion. When both MAO-B inhibitors PF9601N and l-deprenyl were
      added in the incubation medium, at 200 microM concentration, a diminution in the
      dopamine content was observed. The decrease in dopamine content was partially
      calcium dependent and showed a different mechanism between both compounds. When 1
      mM concentration EGTA was added at the Krebs incubation medium without calcium,
      dopamine content was partially recovered, being not affected in case of l
      deprenyl. When 50 microM dantrolene (a calcium vesicular release inhibitor) was
      added in the Krebs incubation medium without calcium, dopamine was partially
      recovered for l-deprenyl, being not affected in case of PF9601N. These data
      indicate that dopamine release is extracellular calcium dependent in case of
      PF9601N, whereas l-deprenyl depends on calcium intracellular origin.

PMID- 11225515
TI  - MAO-A and MAO-B localisation in human lung and spleen.
AB  - Localisation of MAO-A and -B in human lung and spleen was studied by
      immunohistochemistry. The primary antibodies used were mouse monoclonal anti
      human MAO-A (6G11/E1) and anti-human MAO-B (3F12/G10/2E3). Samples of lung and
      spleen were obtained from 6 routine autopsy cases. Both immunoreactivities showed
      a homogeneous distribution in lung, where all cell types had both MAO-A and -B
      staining. In spleen MAO-A and -B showed a very weak immunoreactivity, which was
      restricted to smooth muscle cells and reticular cells of the white pulp. These
      data represent the most comprehensive study of MAO-A and -B localisation in the
      two tissues.

PMID- 11225516
TI  - Apoptotic and antiapoptotic effect of (-)deprenyl and (-)-desmethyl-deprenyl on
      human cell lines.
AB  - The antiapoptotic effect of (-) deprenyl on human phaeochromocytoma cells after
      serum deprivation has been reported by earlier. Two melanoma (M-1 and HT-2058)
      cell lines were used in our experiments. Serum deprivation for five days resulted
      in excessive number of apoptosis in the cell cultures. Very low doses of (-)
      deprenyl (10(-7)-10(-13) mol) caused an approximately 2 days delay in the onset
      of apoptosis. At the same time, +deprenyl was ineffective. In further experiments
      (-)-deprenyl and (-)desmethyl-deprenyl was administered in higher doses (10(-2),
      10(-3) and 10(-4) mol) to A-2058 melanoma and HT-1080 fibrosarcoma cells in
      culture. In these experiments no serum deprivation was applied and the treatment
      was started 24 hours after plating. Total eradication of the A-2058 cells was
      caused by 10(-2) mol (-)-deprenyl and (-)-desmethyl-deprenyl. The type of cell
      death appeared to be apoptosis. Sixty percent apoptotic ratio was seen 24 hours
      and 72 hours after 10(-3) mol (-)-desmethyl-deprenyl treteatment. The same dose
      of (-)-deprenyl caused 50% apoptosis an 72 h. Only (-)-desmethyl-deprenyl induced
      apoptosis (20%) at 24 hours, in the dose of 10(-4) mol. Interestingly (-)
      deprenyl treatment resulted in 60% apoptosis.

PMID- 11225517
TI  - Effect of MAO inhibitors on the high-affinity reuptake of biogenic amines in rat
      subcortical regions.
AB  - The noradrenaline (NA), dopamine (DA) and serotonin (5HT) reuptake inhibitory
      potency of deprenyl, the highly selective and irreversible inhibitor of MAO-B,
      methamphetamine enantiomers, and some other MAO inhibitors (clorgyline, J-508, J
      511, J-512, J-516, LK-63, U-1424, 2-HxMP) was compared. In vitro hypothalamic NA
      reuptake was inhibited by (+)-, and (-)-methamphetamine, (+)- J-508 and (+)
      deprenyl (IC50: 0.35, 3.5, 17.0 and 17.8 mumol/l, respectively), and U-1424, J
      512, J-516, LK-63 and 2-Hx-MP showed IC50 > 1000 mumol/l. Striatal DA reuptake
      was inhibited by (+)-, and (-)-methamphetamine, (+)-, and (-)-deprenyl and
      clorgyline with IC50 of 0.6, 42.0, 24.0, 98.6 and 27.0 mumol/l, respectively,
      however the other compounds were ineffective. Hippocampal 5HT reuptake was
      slightly inhibited by clorgyline (IC50 205.0 mumol/l), while the other MAO
      inhibitors were devoid of potency. Data suggest that potency and selectivity of
      MAO inhibition and reuptake inhibition are independent features of the compounds,
      and metabolism of deprenyl results in increased noradrenaline and dopamine
      reuptake inhibition.

PMID- 11225518
TI  - The lack of Nurr1 does not effect cholecystokinin mRNA expression in the ventral
      midbrain in newborn mouse.

PMID- 11225519
TI  - Serotonin transporter, serotonin-2A receptor and tryptophan hydroxilase gene
      polymorphisms in depressed suicide victims.

PMID- 11225520
TI  - A molecular element of neuronal response to lysolecithin-induced focal,
      experimental demyelination in rat.

PMID- 11225521
TI  - Neurochemical characterization of kidney regulating brainstem neurons identified
      by pseudorabies transneuronal labeling.

PMID- 11225522
TI  - Neuronal projections from the limbic cortex to the hypothalamic paraventricular
      nucleus: transneuronal retrograde labeling with pseudorabies virus.

PMID- 11225523
TI  - Dental amalgam and mercury in dentistry.
AB  - Mercury in dentistry has re-emerged as a contentious issue in public health,
      predominantly because so many people are inadvertently exposed to mercury in
      order to obtain the benefits of dental amalgam fillings, and the risks remain
      difficult to interpret. This commentary aims to examine the issues involved in
      public policy assessment of the continued use of dental amalgam in dentistry.
      More than 30 per cent of Australian adults are concerned about mercury from
      dental amalgam fillings but only a small percentage report having their amalgam
      fillings removed. The placement of dental fillings nearly halved between 1983 and
      1997, but many millions of dental amalgam fillings exist in the Australian
      community. These fillings release mercury (mercury vapour or inorganic ions) at a
      low level (about 2-5 micrograms/day in an adult). Evidence on the health effect
      of dental amalgams comes from studies of the association between their presence
      and signs or symptoms of adverse effects or health changes after removal of
      dental amalgam fillings. More formal risk assessment studies focus on
      occupational exposure to mercury and health effects. Numerous methodological
      issues make their interpretation difficult but new research will continue to
      challenge policymakers. Policy will also reflect prudent and cautious approaches,
      encouraging minimization of exposure to mercury in potentially more sensitive
      population groups. Wider environmental concerns and decreasing tolerance of
      exposure to other mercury compounds (for example, methylmercury in seafoods) will
      ensure the use of mercury in dentistry remains an issue, necessitating dentists
      keep their patients informed of health risks and respect their choices.

PMID- 11225524
TI  - Dental caries is a preventable infectious disease.
AB  - Dental caries is the most common infectious disease affecting humans. The
      principal causative agents are a group of streptococcal species collectively
      referred to as the mutans streptococci of which Streptococcus mutans and
      Streptococcus sobrinus are the most important agents of human caries. This review
      outlines what is currently known about these ubiquitous pathogens and discusses
      novel methods for elimination of these bacteria from dental plaque.

PMID- 11225525
TI  - The environmental effects of dental amalgam.
AB  - Dental amalgam is one of the most commonly used materials in restorative
      dentistry. However, one of its major components, mercury, is of particular
      concern due to its potential adverse effects on humans and the environment. In
      this review, the environmental impact of dental amalgam will be discussed, with
      particular reference to the effects attributed to its mercury component. Mercury
      commonly occurs in nature as sulfides and in a number of minerals. Globally,
      between 20,000-30,000 tons of mercury are discharged into the environment each
      year as a result of human activities. According to a recent German report,
      approximately 46 per cent of the freshly triturated amalgam is inserted as new
      amalgam restorations and the rest is waste. Depending on the presence of an
      amalgam separating unit, some of the generated amalgam-contaminated sludge is
      discharged into the sewage system. Lost or extracted teeth with amalgam fillings
      and amalgam-contaminated waste, such as trituration capsules and cotton rolls are
      discharged with the solid waste and, in most instances, are incinerated. Use of
      disinfectants containing oxidizing substances in dental aspirator kits may
      contribute to remobilization of mercury and its subsequent release into the
      environment. Nevertheless, dental mercury contamination is only a small
      proportion of terrestrial mercury (3-4 per cent), which is quite insignificant
      compared with industrial pollution and combustion of fossil fuels by vehicles.
      The environmental impact of dental mercury is mainly due to the poor management
      of dental amalgam waste. Proper collection of mercury-contaminated solid waste
      prevents the release of mercury vapour during combustion. In addition, the use of
      amalgam separating devices reduces the amount of amalgam-contaminated water
      released from dental clinics.

PMID- 11225526
TI  - Orofacial prosthesis design and fabrication using stereolithography.
AB  - The use of stereolithography for the manufacture of implantable prostheses is
      relatively new. Until now, its use with regard to mandibular resection has been
      to produce pre-operative models that allow more sophisticated planning of the
      contour and better preparation of the metallic framework to be implanted. This
      framework rejoins the sections of the mandible, returning some function, but
      providing no soft tissue support. Hence, the aesthetic results are not optimal.
      The aim of this study was to investigate the accuracy with which a
      stereolithographic model could be made to completely reunite both surfaces of the
      resected mandible and restore full contour. The design and fabrication of a
      mandibular prosthesis utilizing CAD/CAM technology and stereolithography is still
      in the early stages, but initial results indicate that with further research and
      better tools this could provide a new approach to mandibular resections,
      providing better aesthetic results.

PMID- 11225527
TI  - Australian dentists' views on toothbrush wear and renewal.
AB  - The purpose of this study was to survey the views of Australian dentists on
      toothbrush wear, toothbrush renewal periods and recommendations to patients and
      to investigate the relationship between dentists' views on patients' toothbrush
      renewal intervals and dentists' own renewal habits. Questionnaires were mailed to
      5,596 Australian general dental practitioners and replies received from 3,406 (61
      per cent response rate). The majority of respondents (85.7 per cent) felt
      patients should renew their toothbrushes more often. However, only 45.3 per cent
      usually made a recommendation to their patients as to when they should renew
      their toothbrush and only 41.7 per cent thought patients actually followed such
      recommendations. Most respondents (56.6 per cent) thought the average adult
      patient should renew a toothbrush every two-three months. A renewal period of one
      month or earlier was recommended by 23.8 per cent of dentists; four-five months
      by 8 per cent; and six months or longer by 11.5 per cent. A highly significant
      correlation was found between the renewal periods recommended for patients and
      the intervals selected by the dentists for their personal brushes (p < 0.001; chi
      square test). Bending and splaying of bristles was the sign identified by the
      majority of dentists (70 per cent) as indicating the need for a new brush. The
      findings suggest dentists' recommendations concerning toothbrush renewal
      intervals may be based on their own toothbrush renewal habits. It is also
      concluded that dentists think patients comply poorly with their recommendations
      on toothbrush renewal.

PMID- 11225528
TI  - Safety issues relating to the use of hydrogen peroxide in dentistry.
AB  - Hydrogen peroxide is used widely in professionally and self-administered
      products. Hydrogen peroxide is a highly reactive substance which can damage oral
      soft tissues and hard tissues when present in high concentrations and with
      exposures of prolonged duration. This report provides an overview of health
      issues relating to the use of hydrogen peroxide, with an emphasis on safety with
      prolonged exposure to low concentrations of peroxide products. There is good
      evidence for the safety of hydrogen peroxide when used at low concentrations on a
      daily basis over extended periods of time, in self-administered oral health care
      products such as dentifrices and mouthrinses. These low concentrations neither
      damage oral hard or soft tissues, nor do they pose a significant risk of adverse
      long-term effects. Caution should be exercised with the increasingly higher
      concentration peroxide products used for 'walking' or 'power' bleaching due to
      the possibility of chemical irritation of oral soft tissues with injudicious use.
      The volumes of material and application times should be controlled carefully.
      Thorough education of patients is particularly important with self-applied gels
      because of the lack of professional supervision with such products. Such
      education is part of the duty of care of the dentist who supplies bleaching gels
      for at-home use.

PMID- 11225529
TI  - An interdisciplinary approach to the management of complex medical and dental
      conditions.
AB  - Dental and medical practice often requires an interdisciplinary approach
      integrating the knowledge, skills and experience of all the disciplines of
      dentistry, medicine and its associated fields into comprehensive treatment to
      maximize results. Rapid and comprehensive scientific and technological advances
      have made it difficult for dental and medical practitioners to keep up to date in
      their fields; thus, to decrease practitioner frustration and increase patient
      benefits, an interdisciplinary approach has become essential. This report
      illustrates how therapy was coordinated for a young medically compromised patient
      with dental phobia and significant dental problems. The latest advances in dental
      techniques and materials, medical technology and pharmacology are highlighted.
      The communication and cooperation of team members with each other and with the
      patient and guardians is illustrated. The astute observation by a medical
      practitioner in an unrelated discipline led to the improvement in the quality of
      life for a patient.

PMID- 11225530
TI  - A late developing mandibular premolar supernumerary tooth.
AB  - This paper presents a case of a patient who developed a mandibular premolar
      supernumerary tooth between the age of 11 and 20 years. Evidence for the late
      development of the supernumerary tooth comes from consecutive panoramic
      radiographs. A review of the international literature concerning late developing
      supernumerary teeth is included.

PMID- 11225531
TI  - Conservative management of lower second premolar impaction.
AB  - Lower second premolars account for approximately 24 per cent of impactions,
      excluding third molars, even though most reports in the literature relating to
      impacted teeth address the maxillary canine, with relatively few reports on the
      lower second premolar. Conservative management involves surgical exposure of the
      crown, however, subsequent premolar eruption is unpredictable. A case is
      described in which removal of a deciduous second molar was followed by eruption
      of an unfavourably inclined premolar located deep within the alveolus. Sufficient
      time must be allowed for eruption and in the present case 16 months elapsed
      before the tooth had erupted to the level of the occlusal plane.

PMID- 11225532
TI  - Quinine induced coagulopathy--a near fatal experience.
AB  - A 67 year old man presented to his local dentist for restorative treatment. He
      stated he was fit and well and denied taking any medications. When he was given
      an inferior alveolar nerve block, excessive bleeding was noted at the injection
      site and the dentist advised the patient see an oral and maxillofacial surgeon.
      An appointment was made for the patient but he did not attend. Three days later,
      he presented with evidence of massive deep haemorrhage to the point of airway
      compromise. He underwent hospital admission, early intubation, intensive care for
      nine days and hospitalization for six weeks. The cause of his bleeding was a
      severe thrombocytopoaenia, induced by chronic ingestion of quinine. He was self
      medicating with this to relieve muscular cramps. Despite this experience, the
      patient continued to deny that quinine was the cause of his problem and that he
      had failed in his obligations to advise the dentist of his drug history. Dentists
      need to be alert to the risk that patients may not reveal their true medical
      history. There are, however, obligations on the dentist to ensure the accuracy of
      information the patient gives and to ensure that patients whom they believe are
      at risk follow their advice. Teamwork and skillful airway management prevented
      this patient's demise.

PMID- 11225533
TI  - Continuing dental education in osseointegrated implants. A survey.
AB  - A survey of participants in a continuing education course in osseointegrated
      implants was carried out to determine dentists' attitudes toward such courses and
      how they were integrating implants into their everyday practice. The results
      indicated, despite the intense program, very few general dentists who attended
      such a course chose to actively participate in implant placement and a moderate
      number chose to carry out prosthetic restoration. Those who attended such courses
      appeared satisfied with the course content, appreciated the difficulties involved
      with implant placement and restoration and generally chose to refer such cases to
      appropriate specialists for management. This pilot study confirms dental implants
      are a popular and accepted mode of therapy. However, general dental practitioners
      who take the time to undergo specific training in osseointegrated implants appear
      to be less inclined to actively participate in the placement (surgery) of
      implants. Following appropriate training, many general practitioners felt
      comfortable in performing the restorative/prosthetic aspect of implant treatment
      for single tooth rather than partial or full denture cases. In conclusion, while
      continuing education courses in osseointegrated implants are becoming
      increasingly popular, this survey indicates participants become aware of the
      complexity of the procedures involved and tend to actively participate mainly in
      the prosthetic reconstruction of simple cases.

PMID- 11225534
TI  - Dental root surface caries study.

PMID- 11225535
TI  - Thin section nostalgia.

PMID- 11225536
TI  - Australian response to BSE.

PMID- 11225537
TI  - Comment on preventive dentistry reply.

PMID- 11225538
TI  - Comment on tooth loss and implant replacement.

PMID- 11225539
TI  - Functional appliances critique.

PMID- 11225540
TI  - Antibiotic prescribing.

PMID- 11225541
TI  - Rooting out errors: blame is giving way to prevention.

PMID- 11225542
TI  - Final privacy reg has strict rules for patient information.

PMID- 11225543
TI  - Neutral zone cuts sharps injuries.

PMID- 11225544
TI  - Off-shift choices help to keep nurses.

PMID- 11225545
TI  - Are plastic trays a friend or foe?

PMID- 11225546
TI  - MedPAC nixes pay for recovery care.

PMID- 11225547
TI  - Cataract variation likely to continue.

PMID- 11225549
TI  - Outsourcing likely for single-use items.

PMID- 11225548
TI  - Outpatients need nursing's support.

PMID- 11225550
TI  - Sharps safety must involve the staff.

PMID- 11225551
TI  - E-health: eight power factors, three scenarios.
AB  - The Internet may--or may not--revolutionize health care. It all depends on the
      degree of public acceptance, industry investments, physician behavior, and other
      critical factors. How they play out will likely determine the speed and extent of
      the changes ahead.

PMID- 11225552
TI  - E-health & pharmaceuticals.
AB  - Drug firms are integrating technology into the continuum of care. They're
      enlisting physicians to use their technology in prescribing medications,
      reporting clinical data, and learning about new drugs. They're also building a
      loyal customer base, and they're doing it smartly.

PMID- 11225553
TI  - The latest revolution. What solutions will technology offer?
AB  - What can we expect of the "typical" health care organization in five years? As
      basic functions are widely adopted, the "e" will begin to drop from e-health.
      Consumers will demand free medical content, basic self-service tools, and other
      online functions and services.

PMID- 11225555
TI  - Partnerships between academic medical centers & rural communities.

PMID- 11225554
TI  - Managing the future.
AB  - Successful systems are aligning technology with business strategy. They know
      their position on the technology spectrum defines their culture, image, and
      relationship to patients, providers, and payers. So they're prioritizing their
      technology investments carefully.

PMID- 11225556
TI  - Preparing for terrorism and hazardous material exposures.

PMID- 11225557
TI  - A core strategy--developing a brand. A health care organization that builds
      strong brand loyalty will ensure its position for the future.

PMID- 11225558
TI  - What the health care ranking lists can--and can't--do.

PMID- 11225559
TI  - Best practices. Critical indicators of enterprise performance.

PMID- 11225560
TI  - C. A. M. Complementary & alternative medicine. Mission & money in integrative
      medicine.

PMID- 11225561
TI  - The rise and fall and rise of e-health.

PMID- 11225562
TI  - CEO of a surgical hospital development and management company committed to
      customer service.

PMID- 11225563
TI  - e-gads!

PMID- 11225564
TI  - Effect of clinoptilolite on performance of broiler chickens during experimental
      aflatoxicosis.
AB  - 1. The amelioration of aflatoxicosis in broiler chickens was examined by feeding
      2 concentrations of natural zeolite (clinoptilolite). Clinoptilolite (CLI),
      incorporated into the diet at 15 and 25 g/kg, was evaluated for its ability to
      reduce the deleterious effects of 2.5 mg total aflatoxin (AF; 76.40% AFB1, 16.12%
      AFB2, 6.01% AFG1 and 1.47% AFG in diet on growing broiler chicks from 1 to 21 d
      of age. A total of 360 broiler chicks were divided into 6 treatment groups (6
      replicates of 10 broilers each): control, AF, CLI (15 g/kg), AF plus CLI (15
      g/kg), CLI (25 g/kg), and AF plus CLI (25 g/kg).   2. Compared to controls, the
      treatment had significantly decreased body weight gain from week 1 onwards. The
      adverse effect of AF on food consumption (8.0%) and food conversion ratio (8.3%)
      was also shown over the entire 21-d feeding period.   3. The addition of CLI (15
      g/kg) to an AF-containing diet significantly reduced the deleterious effects of
      AF on food consumption and body weight gain. Food conversion ratio was also
      slightly improved by adding CLI (15 g/kg) to AF-containing diets. Food
      consumption, body weight gain and food conversion ratio values were rendered
      numerically intermediate between AF and control groups by the addition of CLI (25
      g/kg) to the AF-containing diet.   4. The addition of CLI (both 15 and 25 g/kg)
      to the AF-free diet did not produce any significant changes compared with the
      controls, except for decreased total food consumption in the CLI (25 g/kg)-alone
      group.   5. These results suggest that CLI (15 g/kg) addition effectively
      diminished the detrimental effects of AF on the values investigated. Also, the
      lower dietary concentration of CLI (15 g/kg) was more effective than the greater
      concentration against the adverse effects of AF on the variables investigated in
      this study.

PMID- 11225565
TI  - Inhibition of human cytochrome P450 isoforms by nonnucleoside reverse
      transcriptase inhibitors.
AB  - The capacity of three clinically available nonnucleoside reverse transcriptase
      inhibitors (NNRTIs) to inhibit the activity of human cytochromes P450 (CYPs) was
      studied in vitro using human liver microsomes. Delavirdine, nevirapine, and
      efavirenz produced negligible inhibition of phenacetin O-deethylation (CYP1A2) or
      dextromethorphan O-demethylation (CYP2D6). Nevirapine did not inhibit
      hydroxylation of tolbutamide (CYP2C9) or S-mephenytoin (CYP2C19), but these CYP
      isoforms were importantly inhibited by delavirdine and efavirenz. This indicates
      the likelihood of significantly impaired clearance of CYP2C substrate drugs (such
      as phenytoin, tolbutamide, and warfarin) upon initial exposure to these two
      NNRTIs. Delavirdine and efavirenz (but not nevirapine) also were strong
      inhibitors of CYP3A, consistent with clinical hazards of initial cotreatment with
      either of these drugs and substrates of CYP3A. The in vitro microsomal model
      provides relevant predictive data on probable drug interactions with NNRTIs when
      the mechanism is inhibition of CYP-mediated drug biotransformation. However, the
      model does not incorporate interactions attributable to enzyme induction.

PMID- 11225566
TI  - Effect of fluoxetine on carvedilol pharmacokinetics, CYP2D6 activity, and
      autonomic balance in heart failure patients.
AB  - The objective of this study was to examine the pharmacokinetic and
      pharmacodynamic consequences of concomitant administration of fluoxetine and
      carvedilol in heart failure patients. Fluoxetine (20 mg) or matching placebo was
      administered in a randomized, double-blind, two-period crossover study to 10
      patients previously identified as extensive metabolizers of CYP2D6 substrates.
      Patients were maintained on a carvedilol dose of 25 or 50 mg bid and given
      fluoxetine/placebo for a minimum of 28 days. Plasma was collected over the 12
      hour carvedilol dosing interval, and the concentrations of the R(+) and S(-)
      enantiomers of carvedilol were measured. CYP2D6 phenotype was assessed during
      each study period using dextromethorphan (30 mg). Changes in autonomic modulation
      between study periods were measured by heart rate variability in the time and
      frequency domains using ambulatory electrocardiographic monitoring. Compared to
      placebo, fluoxetine coadministration resulted in a 77% increase in mean (+/- SD)
      R(+) enantiomer AUC0-12 (522 +/- 413 vs. 927 +/- 506 ng.h/mL, p = 0.01) and a
      nonsignificant increase in S(-) enantiomer AUC (244 +/- 185 vs. 330 +/- 179
      ng.h/mL, p = 0.17). Mean apparent oral clearance for both enantiomers decreased
      significantly with fluoxetine administration (R(+): 10.3 +/- 7.2 vs. 4.5 +/- 2.2
      mL/min/kg; S(-): 22.5 +/- 12.3 vs. 12.6 +/- 7.4 mL/min/kg; p = 0.004 and 0.03,
      respectively). No differences in adverse effects, blood pressure, or heart rate
      were noted between treatment groups, and there were no consistent changes in
      heart rate variability parameters. In conclusion, fluoxetine administration
      resulted in a stereospecific inhibition of carvedilol metabolism, with the R(+)
      enantiomer increasing to a greater extent than the S(-) enantiomer. However, this
      interaction was of little clinical significance in our sample population.

PMID- 11225567
TI  - Molecular and biological characterization of a zonula occludens-1 homologue in
      Hydra vulgaris, named HZO-1.
AB  - Zonula occludens-1 (ZO-1) is one of the earliest identified molecular components
      of tight junctions. Sequence analysis has placed ZO-1 into the broader membrane
      associated guanylate kinase (MAGUK) protein family that contains such diverse
      members as post-synaptic density 95 (PSD-95), Drosophila discs large tumor
      suppressor gene product (dlg-A), p55, and TamA. Studies in both vertebrates and
      invertebrates have established that the MAGUK family is involved in a wide
      variety of cellular functions. These functions involve the regulation of such
      cellular processes as: (1) tight junction formation, (2) cell proliferation, (3)
      cell differentiation, and (4) neuronal synapse transmission. Extending these
      studies, we report the presence of a ZO-1 homologue in Hydra vulgaris, a member
      of the Cnidaria, the second oldest phylum of the animal kingdom. Hydra ZO-1 (HZO
      1) is encoded by a single messenger RNA (mRNA) of approximately 6.0 kb that
      contains an open reading frame of 5,085 bp. The 191 kDa predicted protein
      consists of a characteristic MAGUK domain structure, including three PSD
      95/SAP90, discs-large, ZO-1 (PDZ) domains, a src homology (SH3) domain, and a
      guanylate kinase (GUK) domain. Western blot analysis using an antibody generated
      from a synthetic peptide designed from the HZO-1 sequence confirmed the presence
      of a Hydra protein of the appropriate mass. While whole mount in situ
      hybridization determined that HZO-1 mRNA was expressed along the entire
      longitudinal axis of Hydra, cross-sectional analysis established that HZO-1 mRNA
      expression was restricted to the ectoderm or outer cell layer of the organism's
      epithelial bilayer. Consistent with this mRNA expression pattern,
      immunofluorescence studies localized HZO-1 protein to the apical plasma membrane
      of ectodermal cells. It is unclear what role HZ0-1 has in the cellular physiology
      of Hydra; however, immunolocalization studies indicate a conserved plasma
      membrane-associated function(s), as reported for its counterparts in other
      invertebrate and vertebrate species. These studies establish that the MAGUK
      family of proteins with a membrane-associated function arose early during
      metazoan evolution, even before the divergence of protostomes and deuterostomes.

PMID- 11225568
TI  - When to eat dirt.

PMID- 11225569
TI  - NHS Direct. Website does not always take symptoms seriously enough.

PMID- 11225570
TI  - NHS Direct. Will website help people or scare them?

PMID- 11225571
TI  - Is there a place for inhaled nitric oxide in the therapy of massive pulmonary
      embolism?

PMID- 11225572
TI  - Different mutation of the XLRS1 gene causes juvenile retinoschisis with retinal
      white flecks.

PMID- 11225573
TI  - An Australian family with macular dystrophy linked to autosomal recessive
      alopecia universalis.

PMID- 11225574
TI  - Cystic epithelial growth after penetrating keratoplasty: successful curative
      treatment by block excision.

PMID- 11225576
TI  - Clinical manifestations of protein C deficiency: a spectrum within one family.

PMID- 11225575
TI  - Ocular scleromalacia caused by leishmaniasis: a rare cause of scleral
      perforation.

PMID- 11225577
TI  - Spontaneous consecutive extropia in children with motor fusion.

PMID- 11225578
TI  - Practice patterns of pneumatic retinopexy in the United Kingdom.

PMID- 11225579
TI  - Does instilling proxymetacaine before cyclopentolate significantly reduce
      stinging? The implications of paediatric cycloplegia.

PMID- 11225580
TI  - Delayed quinine toxicity mimicking open angle glaucoma.

PMID- 11225581
TI  - Progressive assessment of age related macular degeneration using an artificial
      neural network approach.

PMID- 11225582
TI  - Iatrogenic keratectasia after phototherapeutic keratectomy.

PMID- 11225583
TI  - Selected honors, positions and bibliography of Richard A. Posner.

PMID- 11225584
TI  - Prospective randomized trial of low-pressure pneumoperitoneum for reduction of
      shoulder-tip pain following laparoscopy (Br J Surg 2000;87:1161-5).

PMID- 11225585
TI  - In memoriam. Tribute to Rene Favaloro, pioneer of coronary bypass.

PMID- 11225586
TI  - In memoriam. Addendum on Rene Favaloro.

PMID- 11225587
TI  - In memoriam. Tribute to Ake Senning, pioneering cardiovascular surgeon.

PMID- 11225589
TI  - What our patients say.

PMID- 11225591
TI  - Cardiac stimulation in heart failure: are we going too fast, are we going too
      far?

PMID- 11225592
TI  - How to ablate typical 'slow/fast' AV nodal reentry tachycardia.

PMID- 11225590
TI  - Metastatic MHC class I-negative mouse cells derived by transformation with human
      papillomavirus type 16.
AB  - In the endeavour to develop a model for studying gene therapy of cancers
      associated with human papillomaviruses (HPVs), mouse cells were transformed with
      the HPV type 16 (HPV16) and activated H-ras oncogenes. This was done by
      cotransfection of plasmid p16HHMo, carrying the HPV16 E6/E7 oncogenes, and
      plasmid pEJ6.6, carrying the gene coding for human H-ras oncoprotein activated by
      the G12V mutation, into secondary C57BL/6 mouse kidney cells. An oncogenic cell
      line, designated MK16/1/IIIABC, was derived. The epithelial origin of the cells
      was confirmed by their expression of cytokeratins. No MHC class I and class II
      molecules were detected on the surface of MK16/1/IIIABC cells. Spontaneous
      metastases were observed in lymphatic nodes and lungs after prolonged growth of
      MK16/1/IIIABC-induced subcutaneous tumours. Lethally irradiated MK16/1/IIIABC
      cells induced protection against challenge with 10(5) homologous cells, but not
      against a higher cell dose (5 x 10(5)). Plasmids p16HHMo and pEJ6.6 were also
      used for preventive immunization of mice. In comparison with a control group
      injected with pBR322, they exhibited moderate protection, in terms of prolonged
      survival, against MK16/1/IIIABC challenge (P < 0.03). These data suggest that
      MK16/1/IIIABC cells may serve as a model for studying immune reactions against
      HPV16-associated human tumours.

PMID- 11225593
TI  - Comparison of QT dispersion during atrial fibrillation and sinus rhythm in the
      same patients, at normal and prolonged ventricular repolarization.
AB  - AIMS: Drug-induced increase in QT dispersion has been associated with increased
      risk of ventricular proarrhythmia. The aim of the present study was to compare QT
      dispersion during atrial fibrillation and sinus rhythm in the same patients at
      normal and prolonged ventricular repolarization. METHODS AND RESULTS: Sixty-one
      patients who had had chronic atrial fibrillation for 8 +/- 14 months received a 6
      h infusion of the Ikr-blocker almokalant, the first 90 min of which are used for
      this analysis. The following day, after conversion to sinus rhythm, by almokalant
      (n = 19) or direct current cardioversion (n=42), an identical 90 min infusion was
      administered. Prior to infusion, there was no difference in precordial QT
      dispersion between atrial fibrillation and sinus rhythm (29 +/- 12 vs 36 +/- 17
      ms, P=ns). During infusion, at prolonged repolarization, the increase in QT
      dispersion was greater during sinus rhythm than during atrial fibrillation (58 +/
      49 vs 30 +/- 15 ms, P=0.0011, after 30 min infusion). No correlation was found
      between QT dispersion and the QT or RR interval. CONCLUSION: QT dispersion during
      atrial fibrillation does not differ from QT dispersion during sinus rhythm during
      normal repolarization. while measurement of QT dispersion during prolonged
      repolarization, induced by an Ikr-blocker, yielded larger values during sinus
      rhythm than during atrial fibrillation.

PMID- 11225594
TI  - The molecular genetics of hypertrophic cardiomyopathy: prognostic implications.

PMID- 11225595
TI  - Decremental conduction properties in overt and concealed atrioventricular
      accessory pathways.
AB  - AIM: Most atrioventricular accessory pathways (AV-APs) exhibit Kent bundle
      physiology characterized by fast and non-decremental conduction properties. In
      contrast, atriofascicular APs, which are only capable of reaching slow levels of
      long antegrade decremental conduction, are uncommon. The aim of this study was to
      describe antegrade and/or retrograde AV-APs with unusual decremental properties.
      METHODS AND RESULTS: Five patients with unusual decremental AV-APs underwent
      electrophysiological evaluation and radiofrequency catheter ablation for
      symptomatic tachycardias. Three were found to have structural heart disease, and
      three latent decremental AV-APs in the anterograde and/or retrograde direction
      that could not be demonstrated by routine electrophysiological testing. In Case
      1, a right posteroseptal AV-AP with bidirectionally latent decremental conduction
      was associated with clinical antidromic circus movement tachycardia (CMT)
      mimicking ventricular tachycardia and orthodromic CMT, the latter inducible only
      with isoprenaline. In Case 2, incessant orthodromic CMT was due to a latent
      retrograde left posterolateral AV-AP. In both cases, double atrial responses to a
      single paced ventricular beat, initiating orthodromic CMT, were observed. In Case
      3 with latent preexcitation unmasked by adenosine and atrial pacing, retrograde
      latent decremental conduction over a right posteroseptal AV-AP could be shown
      only with isoprenaline. This patient and the remaining two with overt
      preexcitation demonstrated anterograde decremental AP conduction that was
      discontinuous over a right posteroseptal AV-AP in Cases 3 and 4 and was
      continuous over a midseptal AV-AP in Case 5. In the latter case, the site of
      decremental conduction could be localized at the proximal AP origin. All five AV
      APs were successfully ablated at the annulus level. CONCLUSION: AV-APs with
      unusual decremental properties that are either latent, demonstrable only during
      CMT or overt, exhibiting functional longitudinal dissociation are described.
      These APs could be identified and successfully ablated after detailed
      electrophysiological analysis.

PMID- 11225596
TI  - Sinus node recovery time assessment by the overdrive suppression test employing
      an intravenous injection of disopyramide phosphate.
AB  - Although sinus node recovery time (SNRT) assessment by the overdrive suppression
      test (ODST) is important in detecting sick sinus syndrome (SSS), its sensitivity
      is still inadequate. We have evaluated the effect of intravenous injection (i.v.)
      of disopyramide phosphate (DP) in ODST. The subjects were 30 SSS patients (64.9
      +/- 10.0 <SD> years old). If SNRT was <2,000 ms or the corrected SNRT (CSNRT) was
      < 1,000 ms, ODST was repeated after DP i.v. (2 mg. kg(-1), < or = 100 mg in
      total). Eleven normal subjects (59.3 +/- 9.0 years old) were also studied.
      Although SNRT was <2,000 ms or the CSNRT was < 1,000 ms in 13 of the 30 SSS
      patients (43%), SNRT was prolonged from 1,510 +/- 300ms to 3,400 +/- 1,160 ms
      (P<0.01), and CSNRT from 510 +/- 190 to 2,470 +/- 1,470 ms (P<0.01) after DP i.v.
      in these patients. Thus, SNRT was > or = 2,000 ms and the CSNRT was > or = 1,000
      ms in 27 of 30 SSS patients (90%) after DP i.v. Using a combination of overdrive
      suppression and intravenous injection of disopyramide phosphate, the corrected
      sinus node recovery time was diagnostic (>525 ms) in 29 of the 30 patients (97%).
      In contrast, SNRT and CSNRT were shortened in the normal subjects during ODST
      after DP i.v. (P<0.01). The plasma concentration of DP estimated in nine patients
      was 4.1 +/- 1.0 microg.ml(-1). No serious side effect occurred. ODST employing DP
      i.v. is safe and seems to be highly effective in diagnosing SSS.

PMID- 11225597
TI  - Artifacts recorded through failing bipolar polyurethane insulated permanent
      pacing leads.
AB  - Pacing failure in bipolar systems using polyurethane insulated leads may be
      frequent depending on the type of polyurethane and can cause oversensing and or
      failure to capture. The reason for this failure is often breakage in the inner
      insulation. The aim of this study was to evaluate the signals created by such a
      short circuit. Thirty-seven patients were included in the study, 13 with failing
      leads with polyurethane 80A insulation, 14 with old but normally functioning
      leads and 10 patients with new leads. Artifacts in the form of spikes were
      recorded, during surgical revision, from 11 patients with failing leads (84.6%).
      In patients with normally functioning leads and newly implanted leads no
      artifacts were recorded. A significant decrease in impedance of 373.4 Ohms (99%
      confidence intervals 286.4-460.4, P<0.05) was noted in the failing leads compared
      with a decrease of only 113.0 Ohms (99%, confidence intervals 6.5-219.6, P<0.01)
      in the control leads. The difference between the groups was highly significant.
      In 10 newly implanted and five normally functioning bipolar ventricular leads
      similar artifacts could be created by making intermittent contact between the
      proximal lead connections. Thus, artifacts could be recorded from failing leads
      and from intact leads with artificial intermittent connection at the proximal
      end. Our results suggest that the failure is caused by a short circuit in the
      lead. This finding may have important clinical applications in the follow-up of
      bipolar pacing and defibrillation leads.

PMID- 11225598
TI  - New classification of haemodynamics of vasovagal syncope: beyond the VASIS
      classification. Analysis of the pre-syncopal phase of the tilt test without and
      with nitroglycerin challenge. Vasovagal Syncope International Study.
AB  - We believe that the pattern of blood pressure response to tilt during the time
      preceding the development of the vasovagal reaction may provide adjunctive
      diagnostic information. A group of 101 consecutive patients affected by syncope
      of uncertain origin underwent passive tilt testing for 45 min at 60 degrees
      followed, if negative, by oral (sublingual) trinitroglycerin (TNG) 0.4 microg
      with continuation of the test for 20 min. Three main patterns were observed: the
      classic (vasovagal) syncope pattern was observed in 36 patients who, during the
      preparatory phase, had a rapid and full compensatory reflex adaptation to upright
      position, resulting in stabilization of their blood pressure values until abrupt
      onset of the vasovagal reaction; the dysautonomic (vasovagal) syncope pattern was
      observed in 47 patients in whom steady-state adaptation to upright position was
      not possible. There was thus a progressive fall in their blood pressure until the
      occurrence of a typical vasovagal reaction; the orthostatic intolerance pattern
      was observed in 18 patients in whom there was a progressive fall in blood
      pressure, similar to that of the dysautonomic group, but this was not followed by
      a clear vasovagal reaction. Compared with the classic, the dysautonomic patients
      were older, had a higher prevalence of co-morbidities, a very much shorter
      history of syncopal episodes, and a prevalence of mixed and vasodepressor forms
      of the VASIS classification. The patients with orthostatic intolerance had
      clinical characteristics similar to the dysautonmic group but they could not be
      classified according to the VASIS classification. In conclusion, in patients with
      syncope, a variety of abnormal responses is observed during tilt testing,
      suggesting that different syndromes can be diagnosed by the test. A more
      detailed, although still arbitrary, classification may form the basis of a number
      of future drug and pacemaker trials, as well as help towards a greater
      understanding of the different mechanisms of tilt-induced syncope.

PMID- 11225599
TI  - Exercise-induced neurocardiogenic syncope: clinical data, pathophysiological
      aspects, and potential role of tilt table testing.
AB  - The evaluation of syncope occurring during exercise or occurring spontaneously in
      highly trained individuals presents a unique diagnostic challenge. It is of
      critical importance to exclude potential life-threatening disorders such as
      hypertrophic cardiomyopathy, long QT syndrome, right ventricular dysplasia,
      anomalous coronary artery distribution, valvular heart disease, myocarditis, or
      exercise-induced arrhythmia. This review is not directed towards identifying,
      treating, or determining athletic eligibility of individuals with such disorders.
      Rather, we endeavour to discuss the pathophysiology of exercise-induced
      neurocardiogenic syncope and to address the role of head upright tilt testing in
      evaluating syncope in athletic individuals in whom proper evaluation has excluded
      the presence of ischaemic heart disease or primary structural or electrical heart
      disease.

PMID- 11225600
TI  - Thoracoscopic mapping and cryoablation of right ventricular tachycardia.
AB  - A 14-year-old girl with right ventricular dysplasia and recurrent drug refractory
      ventricular tachycardia underwent thoracoscopic mapping cryoablation. Good access
      to the right ventricular free wall was obtained. We suggest this technique may
      have an important role in the management of patients with right ventricular
      tachycardia.

PMID- 11225601
TI  - Pregnancy with an ICD and a documented ICD discharge.
AB  - We report a successful pregnancy in a patient affected by idiopathic ventricular
      fibrillation 3 years after insertion of an ICD, with a documented defibrillator
      discharge.

PMID- 11225602
TI  - Measurement of mutational flow implies both a high new-mutation rate for
      Huntington disease and substantial underascertainment of late-onset cases.
AB  - We describe a new approach for analysis of the epidemiology of progressive
      genetic disorders that quantifies the rate of progression of the disease in the
      population by measuring the mutational flow. The framework is applied to
      Huntington disease (HD), a dominant neurological disorder caused by the expansion
      of a CAG-trinucleotide sequence to >35 repeats. The disease is 100% penetrant in
      individuals with > or = 42 repeats. Measurement of the flow from disease alleles
      provides a minimum estimate of the flow in the whole population and implies that
      the new mutation rate for HD in each generation is > or = 10% of currently known
      cases (95% confidence limits 6%-14%). Analysis of the pattern of flow
      demonstrates systematic underascertainment for repeat lengths <44. Ascertainment
      falls to <50% for individuals with 40 repeats and to <5% for individuals with 36
      38 repeats. Clinicians should not assume that HD is rare outside known pedigrees
      or that most cases have onset at age <50 years.

PMID- 11225603
TI  - Clinical and biological features of acute myeloid leukaemia occurring as second
      malignancy: GIMEMA archive of adult acute leukaemia.
AB  - Between July 1992 and June 1996, 3934 new cases of acute leukaemia were
      registered in the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto
      (GIMEMA) Archive of Adult Acute Leukaemia. Two hundred cases (5.1%) presented
      with a history of primary malignancy (PM), 179 of which were acute myeloid
      leukaemia (AML). The median age of these cases was significantly higher than that
      of other primitive AML (63 years vs. 57 years; P < 0.001). The number of men was
      significantly lower than the number of women [74/1544 (4.8%) vs. 105/1420 (7.4%);
      odds ratio (OR) 0.63, 95% confidence interval (CI) 0.46-0.87; P < 0.002], as was
      the number of patients aged <65 years [104/1963 (5.3%) vs. 75/1001 (7.5%); OR
      0.69, 95% CI 0.50-0.95; P < 0.01]. An increased incidence of cancer was observed
      among first-degree relatives of patients with AML occurring after a PM (secondary
      AML; sAML) [66/179 (36.9%) sAML vs. 757/2785 (27.2%) de novo AML, age adjusted;
      OR 2.62, 95% CI 1.07-6.42; P < 0.005]. Prevalent types of PM were breast cancer,
      lymphoma and Hodgkin's disease. sAML occurred after a median latency of 52 months
      (range 2-379). Of the 122 patients who received chemotherapy for sAML, 67
      patients (55%) achieved a complete remission (CR), three a partial remission, 15
      (12%) died in induction and 37 (30%) were unresponsive. The median duration of CR
      was 30 weeks (range 4-250). The median overall survival was 7 months (range 1
      196). Comparing acute promyelocytic leukaemia with all other French-American
      British (FAB) groups, a significant increase in CR achievement was observed
      [14/18 (77.7%) vs. 53/101 (52.4%), P < 0.046] as well as in median CR duration
      (55 vs. 24 months, P < 0.02). The analysis of our data suggests that not only
      previous chemotherapy but also genetic predisposition could play a role in the
      pathogenesis of sAML.

PMID- 11225604
TI  - Prenatal diagnosis of severe factor VII deficiency using mutation detection and
      linkage analysis.

PMID- 11225605
TI  - P-selectin and glycoprotein 53 expression in myeloproliferative disorders.

PMID- 11225606
TI  - Microbicides 2000 conference proceedings. March 13-16, 2000, Washington, DC.

PMID- 11225608
TI  - Seismology.     Tectonics, design combine for Indian disaster--more coming.

PMID- 11225607
TI  - "Accepted community standards.".

PMID- 11225609
TI  - Bioinformatics.     Hughes to build own tech research center.

PMID- 11225610
TI  - Organic chemistry.     Sugars join the automation rush.

PMID- 11225611
TI  - Women in science.     College heads pledge to remove barriers.

PMID- 11225612
TI  - Microbiology.     Bakers' yeast blooms into biofilms.

PMID- 11225614
TI  - Math education. Academy report aims to quiet debate.

PMID- 11225613
TI  - Rice genome. Syngenta finishes, consortium goes on.

PMID- 11225615
TI  - Reproductive biology. Cloning: could humans Be next?

PMID- 11225616
TI  - Protein folding. Virtual molecules nail bacteria's weapon.

PMID- 11225617
TI  - Philanthropy. Gates gives booster shot to AIDS vaccines.

PMID- 11225618
TI  - Paleontology. Doubts raised about dinosaur heart.

PMID- 11225619
TI  - Gulf War illness: the battle continues.

PMID- 11225621
TI  - Medicine. Restoring faith in the Pentagon.

PMID- 11225620
TI  - Medicine. Congress explores the scientific fringe.

PMID- 11225622
TI  - Academic harassment. Women faculty battle Japan's koza system.

PMID- 11225623
TI  - German universities. A strong university grows stronger.

PMID- 11225624
TI  - German universities. Humboldt hits the comeback trail.

PMID- 11225625
TI  - German universities. Teaming up to woo young hotshots.

PMID- 11225627
TI  - Atmospheric ethics.

PMID- 11225626
TI  - Sequence data: posted vs.   published.

PMID- 11225628
TI  - Safety of low-cyanide cultivars.

PMID- 11225629
TI  - Museum collections and   conservation efforts.

PMID- 11225630
TI  - Essays on science and society.     Is the genome the secular equivalent of the
      soul?

PMID- 11225631
TI  - Neurobiology. Sniffing out odors with multiple dendrites.

PMID- 11225632
TI  - Cosmology. In support of inflation.

PMID- 11225634
TI  - Semiconductors. Toward functional spintronics.

PMID- 11225633
TI  - Aging.     When do telomeres matter?

PMID- 11225635
TI  - Animal behavior. Nota bene. Texas elephants stomp to victory.

PMID- 11225636
TI  - Protein dynamics: implications for nuclear architecture and gene     expression.

PMID- 11225637
TI  - Is insulin resistance the principal cause of type 2 diabetes?
AB  - The data presented from these recent studies raise serious doubt concerning the
      commonly held view that insulin resistance is the principal cause of type 2
      diabetes: first of all they provide evidence that insulin resistance may not be
      the primary genetic factor for type 2 diabetes; secondly, they demonstrate that
      at least under certain circumstances insulin resistance is not essential for
      diabetes to occur, and then finally, they indicate that insulin resistance may
      not be the predominant factor determining the degree of hyperglycaemia. Although
      these studies suggest that the role of insulin resistance relative to that of
      beta-cell dysfunction in the pathogenesis of type 2 diabetes has been generally
      overestimated, one should not be left with the impression that insulin resistance
      is not important. It is certainly an important factor in determining the degree
      of hyperglycaemia or glucose intolerance present at a given level of beta-cell
      function. The improvement in glycaemic control after weight loss which lessens
      insulin resistance or after the administration of pharmacologic agents that
      improve insulin sensitivity clearly argue that insulin resistance is important in
      this regard. In addition to influencing the severity of glucose intolerance,
      insulin resistance is probably also important in determining the time of onset of
      diabetes. It may do this simply by altering the balance between the body's demand
      for insulin and the ability of the pancreas to provide insulin. It might
      adversely affect beta-cell function in addition to increasing the demand for
      insulin. This concept is schematically represented in figure 3. It is well
      established that beta-cell function normally deteriorates as a function of age
      [41]. Although the prevalence of type 2 diabetes increases as a function of age,
      this by itself obviously does not result in diabetes in the great majority of
      people. In such individuals their insulin sensitivity is sufficient to maintain
      the balance between the supply and demand for insulin above the threshold for
      developing diabetes. Theoretically one may postulate three other situations
      originating with a genetic beta-cell defect: some people may start off life with
      normal beta-cell function but experience a genetically determined accelerated
      deterioration; some people may start off life with reduced beta-cell function
      (e.g. less beta-cell s); still others may start off with reduced beta-cell
      function and have an accelerated rate of deterioration. In each of the above
      situations, at any given level of beta-cell function, the degree of insulin
      resistance present would alter the threshold for developing impaired glucose
      tolerance and ultimately type 2 diabetes; in other words, the greater the insulin
      resistance, the lower the threshold, the earlier the onset and the more severe
      the diabetes will be. It follows therefore that efforts to diminish insulin
      resistance and to preserve beta-cell function should both be beneficial. Weight
      loss and increased physical activity, both of which reduceinsulin resistance,
      have been shown to prevent progression of people with impaired glucose tolerance
      to diabetes. Whether this is simply due to shifting the balance between insulin
      requirements and insulin availability or whether it also involves an improvement
      in beta-cell function and/or prevention of its deterioration remains to be
      clarified. Furthermore, it is not known whether pharmacologic agents which
      improve insulin sensitivity have similar effects.

PMID- 11225638
TI  - Growth factors secreted by fibroblasts: role in healing diabetic foot ulcers.

PMID- 11225639
TI  - Intracerebroventricularly administered corticotropin-releasing factor inhibits
      food intake and produces anxiety-like behaviour at very low doses in mice.
AB  - AIM: Previous studies have demonstrated that corticotropin-releasing factor (CRF)
      produces behavioural, physiological and immunological responses similar to those
      induced by stress. However, these findings have been validated largely in
      laboratory rats. METHODS: We examined the effects of intracerebroventricular
      (i.c.v.) administration of CRF on anxiety and food intake in mice. Using the
      elevated-plus maze, we measured anxiety levels after i.c.v. CRF in mice. We also
      measured food intake for 2 h after i.c.v. CRF. RESULTS: CRF increased the normal
      preference for the closed arms of the maze at a very low dose of 3 pmol,
      indicating an anxiogenic effect. CRF powerfully suppressed food intake at the
      doses of 3-300 pmol for over 2 h. CONCLUSION: Our results demonstrate that i.c.v.
      CRF evokes anxiogenic behaviour and suppresses feeding with the same dose
      response relationships in mice. CRF may thus play a role in integrating the
      overall responses to stress through co-ordinated actions in the brain of this
      species.

PMID- 11225640
TI  - D-tagatose, a novel hexose: acute effects on carbohydrate tolerance in subjects
      with and without type 2 diabetes.
AB  - AIM: D-Tagatose (D-tag), a hexose bulk sweetener, does not affect plasma glucose
      levels when orally administered to rodents. Additionally, D-tag attenuates the
      rise in plasma glucose after mice are administered oral sucrose. The current
      study was undertaken to investigate the acute glycaemic effects of oral D-tag
      alone or in combination with oral glucose in human subjects with and without type
      2 diabetes mellitus. Glycaemic responses to D-tag also were investigated in
      subjects after oral sucrose to examine whether the glucose-lowering effects of D
      tag in rodents may result from a direct inhibition of intestinal disaccharidases.
      METHODS: Eight normal and eight subjects with diabetes mellitus were administered
      75 g of glucose, 75 g of D-tag, or 75 g of D-tag 30 min prior to a 75 g oral
      glucose tolerance test (OGTT). Five patients with diabetes mellitus were
      challenged with a 75 g oral sucrose tolerance test (OSTT) with and without oral
      pre-treatment with 75 g of D-tag. Patients with diabetes mellitus also received
      separate 0, 10, 15, 20 and 30 g of D-tag 30 min prior to a 75 g OGTT. RESULTS:
      Oral loading with D-tag alone led to no changes in glucose or insulin levels in
      either normal patients or those with diabetes mellitus. Pre-OGTT treatment with
      75 g D-tag, however, attenuated the rise in glucose levels in patients with
      diabetes mellitus (p < 0.02 at 60 and 180 min, and p < 0.01 at 120 min). The
      glucose area under the curve (AUC) was reduced significantly also by pre
      treatment with D-tag in a dose-dependent manner in patients with diabetes
      mellitus (p < 0.05 for 10 g D-tag, p < 0.001 for 20 g D-tag, and p = 0.0001 for
      30 g D-tag). In patients with diabetes mellitus 75 g D-tag similarly attenuated
      the rise in glucose following an OSTT (p < 0.01 at 30 min, and p < 0.02 at 60
      min). Pre-treatment with 75 g D-tag also tended to blunt the rise in insulin
      following an OGTT in normal patients (p = 0.07 for insulin AUC) but not patients
      with diabetes mellitus (p = 0.66). Following 75 g of oral D-tag in four normal
      patients, plasma D-tag levels rose to a mean peak level of 3.6 mg/dl at 90 min.
      The administration of 75 g D-tag led to diarrhoea, nausea and/or flatulence in
      100% of subjects. When D-tag was administered at lower doses ranging from 10 g to
      30 g, only three of 10 patients with diabetes mellitus had gastrointestinal
      symptoms which were much more mild than those evoked by 75 g D-tag. CONCLUSIONS:
      These results show that oral D-tag significantly blunts the rise in plasma
      glucose seen after oral glucose in patients with diabetes mellitus in a dose
      dependent manner without significantly affecting insulin levels. The minimal
      elevation of plasma D-tag levels in normal patients and the adverse
      gastrointestinal effects seen following larger doses of D-tag support poor
      absorption of this hexose and suggest that D-tag may act by attenuating glucose
      absorption in the intestine. D-tag may be a useful therapeutic adjunct in the
      management of type 2 diabetes mellitus.

PMID- 11225641
TI  - Unfavourable impact of growth hormone (GH) discontinuation on body composition
      and cholesterol profiles after the completion of height growth in GH-deficient
      young adults.
AB  - AIM: Growth hormone (GH) plays an important role in the regulation of body
      composition and metabolism. GH deficiency is associated with obesity and
      hypercholesterolemia, which respond to GH treatment. In this study we evaluated
      changes in body composition and cholesterol profiles after discontinuation of GH
      therapy to assess atherogenic risk factors in GH-deficient patients. METHODS: We
      studied 18 male patients with GH deficiency 17-20 years of age at the time of
      discontinuing GH therapy. Body composition and cholesterol were measured 6 months
      before discontinuation of GH therapy with a weekly dose of 0.5 IU/kg
      (approximately 0.19 mg/kg), and immediately, 2 months, and 6 months after the end
      of GH therapy. RESULTS: Two months after termination of GH therapy the percentage
      of body fat and fat mass increased from 7.4% to 9.4% and from 3.8 kg to 5.0 kg,
      respectively, and remained high thereafter. Lean body mass decreased gradually,
      but the change was not significant. Lean body mass: fat mass ratio decreased from
      14.7 at termination of GH therapy to 10.9 at the end of study. Total cholesterol
      (TC) showed a significant linear increase from 156 mg/dl immediately after
      discontinuation to 169 mg/dl 6 months after discontinuation of GH, whereas high
      density lipoprotein cholesterol (HDLC) showed no change during the study. The TC
      to HDLC ratio showed a slight but insignificant trend toward an increase. There
      were no significant changes in any variables during the last 6 months of GH
      therapy. CONCLUSION: GH therapy in patients with GH deficiency can reduce risk
      factors for obesity-related diseases and atherosclerosis. These beneficial
      effects are reversed after discontinuation of GH therapy. Further long-term
      studies of the effects of the GH withdrawal on lipid profiles, adiposity and life
      expectancy must be performed.

PMID- 11225642
TI  - A new hope in the nightmare of diabetic orthostatic hypotension: the midodrine
      fludrocortisone association.

PMID- 11225644
TI  - Highlights from the 35th meeting of the EASD. European Association for the Study
      Diabetes.

PMID- 11225646
TI  - Clinical management of diabetic nephropathy.
AB  - From the viewpoint of nephrologists dealing with diabetic patients with ESRD and
      the associated complications and devastating prognosis, the need to reduce the
      incidence, and delay the rate of progression of diabetic nephropathy is obvious.
      Studies published within the last year have provided support for views that seem
      intuitively obvious; that improved glycaemic control and reduced blood pressure
      are associated with delayed onset and delayed progression of diabetic
      nephropathy. These reports have also demonstrated the difficulty of achieving
      ideal blood pressure targets and glycaemic control in diabetic patients. Thus,
      even with available therapy it is likely that improved compliance and achieving
      targets will have a major impact on disease outcome. There is evidence in several
      subgroups that ACEi are beneficial over other agents and the favourable side
      effect and efficacy profile of these agents makes it reasonable to suggest that
      they should be used 'first line' in all patients with diabetes unless
      specifically contra-indicated. However, the failure to readily achieve blood
      pressure targets and the need for polypharmacy suggest that novel agents are
      required. We believe that statin therapy will have a major impact on CVD in
      diabetic patients and is also likely to delay progression; studies assessing the
      combined affect of anti-hypertensive and statin therapy specifically on the
      development and progression of diabetic nephropathy will be necessary before
      evidence-based recommendations can be made. The role for newer agents and
      targeting high risk groups using genetic markers remains uncertain but we await
      there development with interest. The future can only get better for patients with
      DN.

PMID- 11225647
TI  - Metabolic effects of moxonidine and other centrally acting antihypertensives.

PMID- 11225648
TI  - Insulin resistance and familial dyslipidaemias.

PMID- 11225649
TI  - Effects of niacin-bound chromium supplementation on body composition in
      overweight African-American women.
AB  - AIM: This pilot study was designed to determine whether 600 microg niacin-bound
      chromium ingested daily over 2 months by African-American women undergoing a
      modest dietary and exercise regimen influences weight loss and body composition.
      METHODS: Twenty overweight African-American women, engaged in a modest diet
      exercise regimen, participated in a randomized, double-blinded, placebo
      controlled, crossover study. They received placebo three times a day (t.i.d.)
      during the control period and niacin-bound chromium, 200 microg t.i.d., during
      the verum period. Control and verum periods were each 2 months in duration. One
      half received placebo first (group 1), the other half received chromium first
      (group 2). Body weights (b.w.) and blood chemistries were measured by routine
      clinical methodology. Fat and nonfat body masses were estimated using
      bioelectrical impedance (electrolipography). RESULTS: In the first group of 10
      women receiving niacin-bound chromium after the placebo period (group 1), b.w.
      loss was essentially the same, but fat loss was significantly greater and non-fat
      body mass loss significantly less with chromium intake. In contrast to the
      previous findings, there was a significantly greater loss of fat in the placebo
      compared to the verum period in the second group of eight women who received
      chromium first (group 2). Blood chemistries were not affected by intake of
      chromium for 2 months. CONCLUSIONS: Niacin-bound chromium given to modestly
      dieting-exercising African-American women caused a significant loss of fat and
      sparing of muscle compared to placebo. Once chromium was given at these dose
      levels, there was a 'carry-over' effect. Blood chemistries revealed no
      significant adverse effects from the ingestion of 600 microg of niacin-bound
      chromium daily over 2 months.

PMID- 11225650
TI  - Role of nitric oxide in renal function in rats with short and prolonged periods
      of streptozotocin-induced diabetes.
AB  - OBJECTIVE: Nitric oxide (NO) has been proposed to play a significant role in
      renal function. In addition, NO production has been found to increase in diabetes
      mellitus. The present study aimed to clarify the mechanism responsible for NO
      action in renal function in rats with short (10 days) or prolonged periods (8
      weeks) of diabetic induction. METHODS: Male Wistar rats were induced to develop
      diabetes mellitus by intraperitoneal injection of streptozotocin (STZ) (65 mg/kg
      b.w.), whereas the age-matched control rats were given normal saline. After
      diabetic induction for 10 days or 8 weeks, the experiment was begun. Three
      consecutive periods of 30 min each, were designed consisting of one control
      period, the first and the second period of L-arginine or L-NAME or insulin
      infusion. Mean arterial pressure (MAP) was determined every 15 min. Arterial
      blood and urine samples were collected to determine the plasma glucose level
      (PG), glomerular filtration rate (GFR), effective renal plasma flow (ERPF), urine
      flow rate (V), urinary protein excretion (Upro), fractional excretion of glucose
      (FEG) and fractional excretion of sodium (FENa) in each period. RESULTS: No
      significant differences of MAP were apparent between control rats and rats with
      diabetic induction. L-arginine infusion had no effect whereas L-NAME markedly
      increased MAP in normal rats and rats after the short period of diabetes
      induction. Pressor response to L-NAME in rats exposed to the prolonged period of
      diabetes induction was lower than that of age-matched control rats. During L-NAME
      infusion, the PG level significantly declined from 394.9+/-13.1 - 338.0+/-14.1
      mg/dl and from 399.9+/-7.9 - 354.3+/-18.8 mg/dl in rats after short and prolonged
      periods of diabetic induction, respectively. GFR significantly increased whereas
      ERPF slightly increased in diabetic rats. The elevation of GFR could be reversed
      by L-NAME or insulin infusion but it increased again after simultaneous infusion
      of insulin and glucose. Increases in V, the Upro and FEG without changes of FENa,
      were apparent in diabetic rats. Either L-arginine or L-NAME infusion could not
      reverse elevations of V, Upro and FEG. The rise of both V and Upro was reversed
      along with the attenuation of high FEG during insulin infusion, and it rose again
      close to the diabetic level during simultaneous infusion of insulin and glucose.
      Elevation of GFR, V and Upro appeared along with a rise of the PG level by
      approximately 300-350 mg/dl in diabetic rats. CONCLUSIONS: Both NO and
      hyperglycaemia are involved in modulating renal hyperfiltration in diabetic rats.
      The elevations of urine flow rate and urinary excretion of both protein and
      glucose would be expected to represent the reduction of renal tubular
      reabsorption rather than renal hyperfiltration in diabetic rats. NO does not
      participate in the change of renal tubular function in diabetic rats. There was a
      parallel change of urine flow rate and urinary excretion of protein in diabetic
      rats. The rise of the PG level itself would account for the increases of GFR, V,
      Upro and FEG in diabetic rats. Glomerular hyperfiltration, diuresis and
      proteinuria in diabetic rats are not exhibited until the PG level rises to = 300
      350 mg/dl.

PMID- 11225651
TI  - A new air displacement plethysmograph for the determination of Japanese body
      composition.
AB  - A new device based on the plethysmographic measurement of body volume, named the
      BOD POD Body Composition System, was developed for the purpose of estimating body
      composition. The performance, reliability, validity, and clinical application of
      this system were evaluated in Japanese subjects. The coefficient variation (CV:%)
      in same-day tests was 2.48, in three separate-day tests it was 2.27, and for
      independent operators it was 4.53, respectively. There was a clear correlation
      between the results from BOD POD and those from dual energy X-ray absorptiometry
      (DEXA) (r = 0.910, p < 0.01). Finally, the fat body composition of 4489 subjects
      (1499 men, 2990 women) was clinically measured by BOD POD. The findings indicate
      that the BOD POD is a highly reliable and valid method for determining body fat
      percentage. This new method has several advantages, e.g. it is quick, simple to
      operate and may accommodate wide populations.

PMID- 11225652
TI  - Effect of food deprivation on rat plasma estrone fatty acid esters.
AB  - The present study was devised to determine whether the circulating levels of
      estrone fatty esters are modified by 6-48 h starvation in the rat, in parallel to
      changes in fat reserves, as a test to check the plausibility of its function as a
      ponderostat signal in the mammal. Food deprivation resulted in a decrease in
      glucose and triacylglycerols, rapid disappearance of liver glycogen and increases
      in fatty acids and, especially, 3-hydroxybutyrate. Insulin and leptin decreased,
      corticosterone and free estrone increased from 6 h onwards and total estrone
      levels were maintained. Starvation reduced the lipid content of the rat by 25.6%.
      Plasma esterified estrone levels decreased more slowly, by 13% in 48 h, but its
      circulating mass decreased in the same proportion as the total lipid content of
      the rat. The small change in circulating estrone fatty esters is consistent with
      the postulated role of oleoyl-estrone as a medium-term ponderostat signal.

PMID- 11225653
TI  - Defects in insulin action in chronic heart failure.

PMID- 11225654
TI  - Fatty acids and insulin secretion.

PMID- 11225655
TI  - Regulation of the angiotensin AT1 receptor by hypercholesterolaemia.

PMID- 11225656
TI  - Energy metabolism and substrates oxidative patterns in type 2 diabetic patients
      treated with sulphonylurea alone or in combination with metformin.
AB  - OBJECTIVE: To compare substrates oxidative patterns in type 2 diabetic patients
      treated with sulphonylurea alone or in combination with metformin. METHODS:
      Plasma glucose (PG), plasma insulin (PI) and substrates oxidation rates measured
      by indirect calorimetry were compared during a test day at 8.00 a.m. (before
      breakfast), 11.00 a.m. (before the lunch), 2.00 p.m. (2 h after the lunch) and at
      5.00 p.m. in 56 diabetic patients treated with diet (group C, n = 14),
      sulphonylurea (group S, n = 14) or with a sulphonylurea-metformin combination
      (group SM, n = 28). RESULTS: The three groups were comparable for age, body mass
      index (b.m.i.), body composition and PG levels. Mean glucose oxidation (Gox) was
      increased since mean lipid oxidation (Lox) was decreased in group S in comparison
      both with group C (3.02+/-0.08 vs. 2.62+/-0.08 g/min/kg/10(3), p < 0.05; 0.53+/
      0.04 vs. 0.88+/-0.09 g/min/kg/10(3), p < 0.01). Mean Lox was also decreased in
      group S in comparison with group SM (0.88+/-0.06 vs. 0.53+/-0.04
      g/min1/kg1/10(3), p < 0.0001) whereas the difference in Gox between these latter
      two groups was only significant in the basal state (1.94+/-0.17 vs. 2.47+/-0.17
      g/min1/kg1/10(3), p < 0.05). Mean respiratory quotient (RQ) was increased in
      group S (0.90+/-0.01) in comparison both with group C (0.86+/-0.01, p < 0.001)
      and with group SM (0.86+/-0.01, p < 0.001). Mean energy expenditure was lower in
      group S than in group SM (21.4+/-0.6 vs. 23.6+/-0.6 kcal/min/kg/10(3), p < 0.05).
      Substrates oxidative patterns, RQ values and energy expenditure were similar in
      group C and in group SM. CONCLUSIONS: When compared to patients treated with a
      sulphonylurea-metformin bitherapy, patients treated with a sulphonylurea
      monotherapy have a shift in their ratio of fat to carbohydrate oxidation that
      could make body weight loss more difficult in this latter group.

PMID- 11225657
TI  - Erythrocyte insulin receptor tyrosine kinase activity is increased in glyburide
      treated patients with type 2 diabetes in good glycaemic control.
AB  - AIM: The goal of this study was to test the hypothesis that insulin receptor
      tyrosine kinase activity of isolated erythrocytes would be greater in glyburide
      treated patients with type 2 diabetes in good glycaemic control (n = 13) than in
      untreated patients (n = 12) with significant fasting hyperglycaemia. METHODS: The
      two groups were similar in age, sex distribution, and body mass index. By
      selection, glyburide-treated patients had significantly (p < 0.001) lower (mean
      +/- s.e.m.) fasting glucose (6.9+/-0.4 vs. 13.9+/-0.8 mmol/l) and HbA(IC) (7.4+/
      0.2 vs. 11.8+/-0.9%) concentrations. In addition, insulin-stimulated tyrosine
      kinase activity was increased in erythrocytes from glyburide -treated patients (p
      < 0.01). RESULTS: Although insulin receptor number was similar in solubilized
      erythrocytes from the two groups, tyrosine kinase activity per insulin receptor
      was significantly (p < 0.02) greater in erythrocytes from glyburide-treated
      patients with type 2 diabetes. CONCLUSIONS: These findings are quite similar to
      previously published data in metformin-treated patients. As such, it is suggested
      that decreases in insulin receptor tyrosine kinase activity may contribute to the
      loss of insulin sensitivity in hyperglycaemic subjects (glucotoxicity), and that
      an improvement in glycaemic control, irrespective of how it is achieved, will
      help rectify this abnormality.

PMID- 11225658
TI  - Preliminary study of oral polylactide microcapsulated insulin in vitro and in
      vivo.
AB  - AIM: Although the oral route for insulin delivery is the most convenient,
      directly administered oral insulin is degraded by proteolytic enzymes in the
      gastrointestinal (GI) tract. Polylactide was prepared in order to microcapsulate
      the insulin to avoid the enzymes in the GI. The physical characteristics and
      therapeutic possibilities of polylactide microcapsulated insulin (PLA-MCI) were
      studied in vivo and in vitro. METHODS: PLA-MCI was prepared by the two-step
      method of emulsion and solvent extraction. Its morphologic character was observed
      by scanning electron microscopy (SEM). The insulin release profile was determined
      in vitro by insulin measurement and in vivo by blood glucose measurement after
      the force-feeding of 66 diabetic rats. RESULTS: When the microcapsule was
      spherical in shape (diameter 1.5-2.0 microm) the entrapment efficiency of insulin
      was 90% and the loading rate was 10% (W/W). The PLA-MCI (which contained 3.0
      units of insulin/mg of PLA) had peak release rates of 65-74% over 6-8 h in
      phosphate buffer. The same dose of PLA-MCI (insulin 2.5 mg) led to decreased
      responses (from 28% to 68% of control blood glucose levels) in the level of blood
      glucose in 32 rats which had not fasted after they had been force-fed. When 1.2,
      1.8, 2.2 and 3.0 mg of insulin + PLA-MCI was administered to eight diabetic rats,
      their blood glucose levels decreased by 28%, 36%, 54% and 78%, respectively.
      CONCLUSIONS: PLA microcapsules are capable of protecting insulin from degradation
      by the proteolytic enzymes in the GI and of alleviating hyperglycaemia for a
      prolonged period of time in diabetic rats. It may therefore be considered as a
      new carrier for oral insulin.

PMID- 11225659
TI  - Effect of four-week metformin treatment on plasma and erythrocyte antioxidative
      defense enzymes in newly diagnosed obese patients with type 2 diabetes.
AB  - The principal metabolic effect of metformin-an oral antihyperglycaemic agent-is
      the improvement in the sensitivity of peripheral tissues and liver to insulin.
      This study examined the effect of metformin monotherapy on antioxidative defence
      system activity in erythrocytes and plasma in diabetic patients. We studied the
      effect of metformin treatment on the activities of Cu, Zn-superoxide dismutase
      (EC 1. 15. 1. 1.), catalase (EC 1. 11. 1. 6.) and glutathione peroxidase (EC 1.
      11. 1. 9.) in relation to lipid peroxidation products and reduced glutathione
      level in plasma and erythrocytes. In this study we also examined erythrocytes'
      susceptibility to H2O2-induced oxidative stress during metformin therapy.
      Although metformin monotherapy ameliorated the imbalance between free radical
      induced increase in lipid peroxidation (by reducing the MDA level in both
      erythrocytes and plasma) and decreased plasma and cellular antioxidant defences
      (by increasing the erythrocyte activities of Cu, Zn, SOD, catalase and GSH level)
      and decreased erythrocyte susceptibility to oxidative stress, it had negligible
      effect to scavenge Fe ion-induced free radical generation in a phospholipid
      liposome system.

PMID- 11225660
TI  - Clinical trial to pharmacologically reverse the effects of ageing and diabetes.

PMID- 11225661
TI  - Improved recovery of trace amounts of gold (III), palladium (II) and platinum
      (IV) from large amounts of associated base metals using anion-exchange resins.
AB  - The adsorption and desorption behaviors of gold (III), palladium (II) and
      platinum (IV) were surveyed in column chromatographic systems consisting of one
      of the conventional anion-exchange resins of large ion-exchange capacity and
      dilute thiourea solutions. The noble metals were strongly adsorbed on the anion
      exchange resins from dilute hydrochloric acid, while most base metals did not
      show any marked adsorbability. These facts made it possible to separate the noble
      metals from a large quantity of base metals such as Ag (I), Al (III), Co (II), Cu
      (II), Fe (III), Mn (II), Ni (II), Pb (II), and Zn (II). Although it used to be
      very difficult to desorb the noble metals from the resins used, the difficulty
      was easily overcome by use of dilute thiourea solutions as an eluant. In the
      present study, as little as 1.00 microg of the respective noble metals was
      quantitatively separated and recovered from as much as ca. 10 mg of a number of
      metals on a small column by elution with a small amount of dilute thiourea
      solution. The present systems should be applicable to the separation,
      concentration and recovery of traces of the noble metals from a number of base
      metals coexisting in a more extended range of amounts and ratios.

PMID- 11225662
TI  - Oxygen determination in calcium fluoride by deuteron activation analysis.
AB  - Oxygen at trace level in calcium fluoride was determined by instrumental deuteron
      activation analysis based on the 16O(d,n)17F reaction. The irradiations were
      performed with 2.5 MeV deuterons for 60 s at currents ranging from 300 to 500 nA.
      The results obtained for powders and single crystals were compared.

PMID- 11225663
TI  - Evaluation of hydrogen line emission and argon plasma electron concentrations
      resulting from the gaseous sample injection involved in hydride generation-ICP
      atomic emission spectrometric analysis.
AB  - The simultaneous injection of volatile hydride species and hydrogen gas,
      originating in reagent decomposition, was monitored during the operation of a
      continuous hydride generation manifold employed for the determination of trace
      arsenic by HG-ICP-AES. Line and background intensities as well as the FWHM of the
      hydrogen Hgamma and Hdelta lines were measured, and electron number densities
      (ne) estimated from Stark broadening of the line profiles. Results were compared
      with those obtained by conventional pneumatic injection of aqueous solutions.
      Overlapping with atomic nitrogen lines at 410 nm and 411 nm tends to distort the
      Hdelta line profile for the hydrogen-seeded plasma, rendering unreliable results.
      The N I lines seem to be quenched by the presence of water aerosol. More
      consistent results were obtained with the Hgamma line. When no solutions are
      pumped through the hydride generation manifold ("dry" plasma), the measured ne
      value was (1.57 +/- 0.22) x 10(15)cm(-3). Conversely, when the reducing reagent
      flow was replaced by pure water (corresponding to the injection of water vapor in
      equilibrium that is swept by the argon carrier gas passing through the phase
      separator), the electron concentration is 25% higher. In that case the ne value
      agrees between the experimental error with that obtained for a plasma in which a
      water aerosol is introduced at a flow rate of 1 mL/min. An enhancement of 52%
      relative is observed in ne when the system is operated under optimized conditions
      for arsine generation, employing sodium tetrahydroborate in acidic medium as
      reducing agent (i.e. hydrogen seeded plasma). It was also observed that the
      continuum emission near 410 nm for the hydrogen containing plasma correlates with
      the measured electron number density, suggesting that the background enhancement
      under hydride generation conditions may respond to the ion-electron recombination
      mechanism.

PMID- 11225664
TI  - Depth profiling of tin-coated glass by laser ablation inductively coupled plasma
      emission spectrometry with acoustic signal measurement.
AB  - A pulsed, frequency-quadrupled Nd:YAG laser (266 nm, 10 Hz) coupled to an
      inductively coupled plasma atomic emission spectrometer (ICP-AES) was employed
      for depth profiling by ablation of a pyrolytically deposited Sn layer (300 nm) on
      float glass. The procedure consisted of performing individual ablation cycles
      (layer-by-layer). A raster with stroke distance of either 50 microm or 200 microm
      (the raster density) was used as an ablation pattern. The ablation was stopped
      after each cycle and the peak area of the resulting transient optical signal of
      the ICP discharge was plotted against the cycle number. The ablation rate of 90
      to 20 nm per cycle at a low-energy pulse (6 mJ to 1 mJ) was determined by
      profilometry. A beam masking was employed to attenuate the laser shot energy and
      to eliminate the peripheral irregularity of the beam profile. Almost uniform
      removal of the square area (1 mm x 1 mm) of the coating by ablation was achieved
      by combining the fitted raster density, beam masking, focusing and beam energy.
      Different ablation processes were distinguished in cases of the tin coating and
      the uncoated glass surface. While the coating was mainly evaporated, the uncoated
      glass surface exhibited a crumbling associated with production of glass powder.
      This was confirmed by electron microscopy observations. The measured acoustic
      signal followed the behavior of the emission intensity of the Sn line and was
      supposed to be proportional to the amount of Sn vapors. The emission intensity
      depth profile of the Sn coating with graded structure was obtained, which
      qualitatively corresponded with the depth profile measured by secondary ion mass
      spectrometry.

PMID- 11225665
TI  - Age determination of plutonium material in nuclear forensics by thermal
      ionisation mass spectrometry.
AB  - Age is a key parameter when deducing the history of plutonium material, i.e. the
      plutonium produced in the nuclear reactors. This is of vital importance, when a
      smuggled plutonium sample has been seized and the origin has to be determined. A
      methodology is described which allows accurately to determine the age of
      plutonium material by thermal ionisation mass spectrometry using independent
      parent/daughter relations. This has been demonstrated for Reference Materials of
      known ages as well as for real samples. The already established method using
      gamma spectrometry is compared to this.

PMID- 11225666
TI  - Catalytic determination of ultra trace amounts of tellurium by 2.5-order
      differential oscillopolarography.
AB  - A highly sensitive and selective catalytic method with 2.5-order differential
      oscillopolarographic detection is described for the determination of tellurium,
      based on its activation effect on the slow Pd(II)-catalyzed reaction of sodium
      hypophosphite and methyl red in hydrochloric acid medium at 100 degrees C. Methyl
      red exhibited a sensitive 2.5-order differential polarographic wave at -0.35 V
      (vs. SCE) in the supporting electrolyte of pH 5.0 acetate buffer solution and was
      chosen as the indicating component for the indirect determination of tellurium. A
      calibration curve of tellurium in the range of 0.02-2.0 ng mL(-1) was obtained by
      the fixed-time procedure. The detection limit was 0.007 ng mL(-1). Possible
      interferences by co-existing substances were examined. The new method has been
      used to analyze trace tellurium in organs of white mice with satisfactory
      results. RSD was 0.54% to 2.10%, recovery 98.4% to 95.7%. The mechanism is also
      discussed.

PMID- 11225667
TI  - Determination of dichloroacetic acid and trichloroacetic acid by liquid-liquid
      extraction and ion chromatography.
AB  - An extraction technique using MTBE (methyl tert. butyl ether) and reagent water
      in combination with ion chromatography and conductivity determination was
      developed to quantify dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA)
      concentrations in raw water after chlorination. The detection limit of the method
      was 0.45 and 1.50 microg/L for DCAA and TCAA, respectively. Mean values of
      recovery ranged from 90 to 96% for DCAA and 95 to 108% for TCAA. The evaluation
      of recovery and precision of the method indicates that the performance
      characteristics are comparable with gas chromatographic (GC) methods reported in
      literature. In addition, the procedure is simple, fast, and does not need any
      derivatization step. Application of the analytical method to the determination of
      DCAA and TCAA in real samples is shown.

PMID- 11225668
TI  - Detection of bioactive surfactants in aqueous solutions on the basis of H2O2
      voltammetry.
AB  - The voltammetric determination of surfactants at the hanging mercury drop
      electrode in aqueous solutions is described, based on the shift of the peak
      potential deltaEp or the increase of the peak height deltaip of the
      electroreduction of hydrogen peroxide or of the second oxygen reduction step,
      with increasing concentration of surfactants. Although the selectivity of this
      method is rather limited, it could be utilized, e.g., for monitoring the absence
      (or presence) or for the determination of the contents of specified surfactants
      by comparing the obtained deltaip (deltaEp) signal with the reference state of
      the system or with that of a selected reference surface active substance. As
      model surfactants n-octanol, tetrabutylammonium chloride and sodium
      dodecylbenzenesulfonate were used, the regular adsorption behavior of which is
      well known. The method was successfully applied to control the presence of a
      commercial detergent in water for rinsing bottles for infusion solutions.

PMID- 11225669
TI  - Combination of asymmetric flow field-flow fractionation (AF4) and total-reflexion
      X-ray fluorescence analysis (TXRF) for determination of heavy metals associated
      with colloidal humic substances.
AB  - To assess the structural variability of colloidal humic substances and the
      associated heavy metals an off-line coupling of asymmetric flow field-flow
      fractionation (AF4) with total-reflection X-ray fluorescence analysis (TXRF) is
      presented. AF4 allows a rather gentle separation of colloids with a minimum of
      interference and artifacts as no shear forces, drying, or interactions with a
      stationary phase are involved. After a calibration with suitable polymer
      particles of known molecular weight, the molecular weight distribution of
      colloidal humic substances between 1 and 10(3) kDa can be assessed with AF4. The
      combination with TXRF permits a simultaneous multielement analysis after
      preconcentration of samples on the AF4 channel using an optimized buffer. The
      analysis of seepage and sewage water sample and a sewage sludge sample yielded
      continuous distributions of the molecular weight and the associated heavy metals.
      The potential of AF4-TXRF coupling for the study of metal ion exchange equilibria
      with colloids was demonstrated by spiking seepage water with various heavy metals
      and subsequent AF4-TXRF analysis of the heavy metals bound to the colloidal
      fraction (Cu, Cr, Zn, Ni, Co).

PMID- 11225670
TI  - Calibrationless flow-through stripping coulometric determination of arsenic (III)
      and total arsenic in contaminated water samples after microwave assisted
      reduction of arsenic(V).
AB  - A simple and rapid procedure for the calibrationless determination of trace
      concentrations of As(III) and total As in contaminated water samples is
      presented. Arsenic is preconcentrated as As(III) in a flow-through cell with a
      gold plated porous electrode and is then stripped anodically by a constant
      current. The stripping chronopotentiogram is registered and evaluated. The As
      concentration is calculated directly from the combined Faraday's laws. The total
      As content was determined after converting all As species to As(III) by microwave
      assisted reduction with hydrazine hydrochloride in a closed vessel. The detection
      limit was found to be 0.15 microg/L and the linear response range was 0.5 to
      10,000 microg/L. Tap water, surface water, and waste water samples were analyzed.

PMID- 11225672
TI  - Determination of trace elements in marine plankton by inductively coupled plasma
      mass spectrometry (ICP-MS).
AB  - A method has been developed for the determination of 23 elements in marine
      plankton in which inductively coupled plasma (ICP) source mass spectrometry (MS)
      was used to quantify the elements in the solution after digestion in a mixture of
      hydrofluoric and nitric acids in sealed PTFE vessels in a microwave field. The
      procedure was validated by the analysis of a standard reference soil (SRM 2709
      San Joaquin Soil) and a standard reference fresh water plankton (CRM 414). The
      method was applied to the analysis of several marine plankton samples grown under
      controlled conditions including several whose growth media had been enriched with
      selenium. Matrix induced signal suppressions and instrumental drift were
      corrected by internal standardization. The suitabilities of germanium, indium,
      rhodium, scandium and yttrium as internal standard elements were evaluated.
      Neither scandium nor yttrium could be used due to the presence of these elements
      in the samples, germanium was used for the determination of As, Co, Cu, Fe, Ni,
      Se, Si and Zn, indium was used for Al, Ba, Ca, Eu, Sr, and Tl, and rhodium was
      used for Cd, Cr, Hg, Mg, Pb, Sb, Sn, and V. For Al, Ca, Cr, Cu, Fe, Mg, Mn, Ni,
      Si, Sr, V, and Zn internal standardization did not completely compensate for the
      suppressive effect of the heavier elements and the solutions were diluted.
      However, for As, Ba, Cd, Co, Eu, Hg, Pb, Sb, Se, Sn and T1, it was possible to
      obtain accurate results despite the 35-40% suppression in the signals. Isobaric
      overlap was only a problem in the cases of 42Ca and 78Se; 44Ca and 77Se,
      respectively, were used. Memory effects were only observed with Hg for which a
      nitric acid-sodium chloride solution was the most effective wash-out solution.
      The marine plankton samples were able to tolerate a higher concentration of Hg as
      the selenium concentration increased.

PMID- 11225671
TI  - Analytical characterization of municipal solid waste incinerator fly ash. Part
      II.
AB  - The synergy of the micro FT-IR (Fourier Transform-Infrared) and SEM-EDX (Scanning
      Electron Microscopy-Energy Dispersive X-ray) techniques has been shown to be
      particularly helpful and effective for the characterization of inorganic
      compounds in fly ashes. The experimental data obtained by these techniques have
      been interpreted in comparison with those of other techniques. The presence of
      calcium carbonate, some sulfates, ammonium nitrate, calcium hydrogen phosphate,
      some chlorides, some oxides and aluminium silicates have been verified.

PMID- 11225673
TI  - Optimization of microwave-assisted extraction of hydrocarbons in marine
      sediments: comparison with the Soxhlet extraction method.
AB  - Microwave energy was applied to extract polycyclic aromatic hydrocarbons (PAHs)
      and linear aliphatic hydrocarbons (LAHs) from marine sediments. The influence of
      experimental conditions, such as different extracting solvents and mixtures,
      microwave power, irradiation time and number of samples extracted per run has
      been tested using real marine sediment samples; volume of the solvent, sample
      quantity and matrix effects were also evaluated. The yield of extracted compounds
      obtained by microwave irradiation was compared with that obtained using the
      traditional Soxhlet extraction. The best results were achieved with a mixture of
      acetone and hexane (1:1), and recoveries ranged from 92 to 106%. The extraction
      time is dependent on the irradiation power and the number of samples extracted
      per run, so when the irradiation power was set to 500 W, the extraction times
      varied from 6 min for 1 sample to 18 min for 8 samples. Analytical determinations
      were carried out by high-performance liquid chromatography (HPLC) with an
      ultraviolet-visible photodiode-array detector for PAHs and gas chromatography
      (GC) using a FID detector for LAHs. To test the accuracy of the microwave
      assisted extraction (MAE) technique, optimized methodology was applied to the
      analysis of standard reference material (SRM 1941), obtaining acceptable results.

PMID- 11225674
TI  - Collaborative study for the quality control of trace element determinations in
      paint coatings. Part 2. Certification of alkyd resin paint reference materials
      for the migratable contents of trace elements (CRMs 620 and 623).
AB  - This paper describes the preparation, homogeneity studies and certification of a
      series of two paint reference materials (mild steel coated with alkyd resin
      paint, CRM620, and comminuted paint from alkyd resin paint, CRM623) which have
      been produced in support of the EU Toy Safety Directive (88/378/EEC). The
      reference materials have been certified for levels of toxic element migration
      using the method specified in European Standard EN71-3:1994 published by the
      European Committee for Standardization. As such, the certified values, indicative
      values and range data quoted for the reference materials in this paper are method
      specific and relate only to European Standard EN71-3:1994. The paper summarizes
      the analytical work carried out and gives a description of the analytical methods
      used to measure As, Ba, Cd, Cr, Hg, Pb, Sb and Se, the 8 toxic elements specified
      in European Standard EN71-3:1994, in the sample extracts. Descriptions of the
      reference materials, certified values, indicative values together with their
      associated uncertainties or range of laboratory means as appropriate are given.
      The preparation of a (not certified) reference material (beechwood coated with
      nitrocellulose paint, RM621) is also described and assigned values for As, Ba, Cd
      and Se are given. The Hg content could not be certified in any of the reference
      materials, owing to a high dispersion of results.

PMID- 11225675
TI  - Validated method for the determination of platinum from a liposomal source (SPI
      77) in human plasma using graphite furnace Zeeman atomic absorption spectrometry.
AB  - A sensitive analytical method based on flameless atomic absorption spectrometry
      with Zeeman correction has been validated for the quantitative determination in
      human plasma of platinum originating from cisplatin in a liposomal source, SPI
      77. The performance of the method was acceptable over a sample concentration
      range of 0. 125-1.25 micromol platinum/L and the lower limit of quantification
      was determined to be 1.25 micromol platinum/L in undiluted clinical samples. The
      performance data of the assay were investigated using both a calibration curve
      with carboplatin in plasma ultrafiltrate and diluted human plasma samples spiked
      with SPI-77. The recoveries, between-day and the within-day precisions of both
      methods of calibration were not significantly different allowing carboplatin
      ultrafiltrate calibration standards to be used to quantify platinum derived from
      SPI-77 in human plasma. Apparently, the liposomal formulation had no significant
      influence on the determination of platinum. The usefulness of the presented
      method was demonstrated in a phase I clinical and pharmacokinetic study. In
      addition, in vitro experiments were carried out to determine the distribution of
      SPI-77 in blood. The results indicated that platinum from SPI-77 mainly
      concentrates in plasma and that binding to and/or endocytosis in red blood cells
      is negligible.

PMID- 11225676
TI  - Application of magdala red as a fluorescence probe in the determination of
      nucleic acids.
AB  - A fluorescence quenching method was developed for the rapid determination of DNA
      and RNA using magdala red as fluorescence probe. In weakly acidic medium, the
      fluorescence of magdala red (lambdaex/lambdaem = 540/555 nm) can be largely
      quenched by DNA or RNA. The calibration graphs are linear over the range 0.01-1.2
      microg/mL for both calf thymus DNA (CT DNA) and salmon DNA (SM DNA), and 0.015
      1.0 microg/mL for yeast RNA, respectively. The corresponding detection limits are
      6.0 ng/mL for CT DNA, 7.0 ng/mL for SM DNA and 15.0 ng/mL for yeast RNA,
      respectively. CT DNA could be determined in the presence of 20% (w/w) yeast RNA,
      and the relative standard deviation of six replicate measurements is 3.18% for
      400 ng/mL of CT DNA. Interference from coexisting substances in the determination
      of DNA was also examined. Real samples were determined with satisfactory results.

PMID- 11225677
TI  - Determination of molybdenum in the presence of 2-(2-benzothiazolylazo)-p-cresol
      by catalytic-adsorptive stripping voltammetry.
AB  - The adsorptive collection of the molybdenum (VI) complexed with 2-(2
      benzothiazolylazo)-p-cresol (BTAC) coupled with the catalytic current of the
      adsorbed complex at a static mercury drop electrode yields an ultrasensitive
      voltammetric procedure for the determination of molybdenum. Optimal experimental
      conditions were: a stirred acetate buffer 0.2 M (pH 3.5) as supporting
      electrolyte, a BTAC concentration of 1.0 x 10(-6) M as ligand, and a
      concentration of 0.1 M potassium nitrate as the oxidizing agent. In addition, a
      preconcentration potential of -0.080 V vs Ag/AgCl (3 M KCl), equilibration time
      of 15 s, a frequency of 30 Hz, a scan increment of 2 mV, a pulse amplitude of
      0.050 mV, and a drop area of 0.032 cm2 were used. The cyclic voltammogram was
      recorded using a staircase wave with a scan rate of 100 mV/s. The forward scan
      starts at the initial potential of -0.080 V and is reversed at -0.90 V. Using the
      catalytic current at approximately -0.55 V the response to the Mo(VI) was found
      to be linear over a concentration range of 1.0-10.0 microg/L. The limit of
      detection is as low as 6.2 x 10(-10) M with 4 min of preconcentration time. The
      possible interference of other trace ions was investigated. The merits of this
      procedure are demonstrated using of reference samples.

PMID- 11225678
TI  - Generation of a methylbismuth species and its electrothermal vaporization for the
      determination of bismuth by inductively coupled plasma mass spectrometry.
AB  - Inorganic bismuth(III) was converted to a methylbismuth species, possibly
      trimethylbismuth, by a thermochemical reaction with methyllithium. It instantly
      vaporized and was then introduced into the ICP ion source to detect the 209Bi
      signal. Utilizing an exchangeable small sample cuvette placed on the tungsten
      boat furnace for the reaction was very favorable from the viewpoints of easy
      handling, no memory effect, and maintenance of furnace conditions. In this
      manner, the analyte was vaporized at quite a low temperature (150 degrees C). The
      detection limit (3sigma) was 0.13 pg of bismuth and the precision in relative
      standard deviation for 5.0 pg of bismuth was determined to be 3.8% (n = 7).

PMID- 11225679
TI  - Digestion method for silver accumulated in micro-organisms.
AB  - Silver is accumulated to high concentrations in certain microbial strains. Here a
      bomb digestion method is proposed, using HNO3 and HCl, for the extraction and
      digestion of silver and silver compounds from the organic matrix. The method is
      applicable for the quantitative determination of silver by inductively coupled
      plasma atomic emission spectroscopy.

PMID- 11225680
TI  - Comparison of open microwave digestion and digestion by conventional heating for
      the determination of Cd, Cr, Cu and Pb in algae using transverse heated
      electrothermal atomic absorption spectrometry.
AB  - A comparison between open microwave digestion and digestion by conventional
      heating was carried out for the determination of Cd, Cr, Cu, and Pb in two algae
      matrices using transverse heated electrothermal atomic absorption spectrometry
      (ETAAS). A SRM GBW 08504 cabbage was also analysed. These matrices were digested
      with HNO3, using a quartz vessel for microwave digestion and PFA vessel for
      digestion by conventional heating. Cd, Cu and Cr were determined without any
      modifier, while magnesium nitrate and ammonium phosphate mixed modifier was used
      for Pb. Results obtained by both the procedures were in good agreement with each
      other at 95% confidence level, and for SRM GBW 08504 cabbage the values agree
      well with the certified values. The limits of detection obtained were 0.0004,
      0.060, 0.065 and 0.054 mg/kg for Cd, Cr, Cu, and Pb, respectively, using the
      microwave digestion process. The RSD for Cd was 10-15% and for the other elements
      5-10%.

PMID- 11225681
TI  - Analysis of phytochelatins in plant matrices by pre-column derivatization, high
      performance liquid chromatography and fluorescence-detection.
AB  - A sensitive method for the determination of phytochelatins in plant matrices by
      pre-column derivatization with monobromobimane (mBrB) and high-performance liquid
      chromatography (HPLC) on reversed phases and fluorescence-detection has been
      developed and applied to cucumber sprouts (Cucumis sativus) treated with cadmium
      and to the water moss Fontinalis antipyretica (Cd in environmentally-relevant
      concentrations). Whereas phytochelatins were found in the Cd-treated sprouts, no
      phytochelatins were detected in Fontinalis anitipyretica.

PMID- 11225682
TI  - Fourier transform infrared determination of caffeine in roasted coffee samples.
AB  - A new procedure has been developed for the FT-IR determination of caffeine in
      roasted coffee samples. The method involves wetting the coffee samples with a
      0.25 M aqueous NH3 solution, extracting the caffeine with CHCl3, and measuring
      absorbance at 1,659 cm(-1) using a baseline established between 1,900 and 830 cm(
      1). The procedure proposed is fast, only requiring a total extraction time of 16
      min for each sample, and provides a drastic reduction of the organic solvent
      consumed, from the 200 mL diethyl ether and 50 mL CHCl3, required for each sample
      by the reference chromatographic UV-spectrometric determination to only 5 mL
      CHCl3. The method provides a limit of detection of the order of 3 mg L(-1)
      caffeine and a relative standard deviation of 0.4% for 3 independent analyses of
      a sample containing 18.6%mg/g caffeine. The accuracy of the FT-IR procedure was
      evaluated from recovery experiments on spiked samples providing values from 94.4
      to 100.1% and from the comparison of results found for a series of commercial
      samples, by both FT-IR and the official reference procedure.

PMID- 11225683
TI  - Posttraumatic stress disorder and psychosocial functioning after severe traumatic
      brain injury.
AB  - The aim of this study was to investigate the influence of posttraumatic stress
      disorder (PTSD) on rehabilitation after severe traumatic brain injury (TBI).
      Ninety-six patients with severe TBI patients were assessed 6 months after
      hospital discharge with the Posttraumatic Stress Disorder Interview, the
      Functional Assessment Measure (FAM), the Community Integration Questionnaire
      (CIQ), the Overt Aggression Scale (OAS), the General Health Questionnaire (GHQ),
      the Beck Depression Inventory (BDI), and the Satisfaction with Life Scale (SWL).
      PTSD was diagnosed in 27% of patients. Patients with PTSD reported higher scores
      on the GHQ and BDI, and lower scores on the FAM, CIQ, OAS, and SWLS than those
      without PTSD. Effective rehabilitation after severe TBI may be enhanced by
      management of PTSD.

PMID- 11225684
TI  - Social convergence of disturbed eating attitudes in young adult women.
AB  - It has been suggested that a broad range of social factors influence disturbed
      eating attitudes, but there has been relatively little investigation of the role
      of peer influence. Drawing from social identity theory, this longitudinal study
      of a nonclinical group of women examined whether social proximity results in a
      convergence of eating psychopathology over time. Forty-one nonclinical women
      (living in 11 communal apartments) completed the Eating Disorders Inventory (EDI)
      at three time points (1 week after moving in, 10 weeks later, and a further 14
      weeks later). The women's eating and related attitudes were compared across the
      three time points. Then divergence scores were calculated (showing the spread of
      EDI scores within each apartment) and compared across the three time points. The
      spread of scores within the apartments changed significantly, indicating some
      convergence in those attitudes that are socially valued (restrictive attitudes;
      body concerns) and divergence in those attitudes that are not socially valued
      (bulimia). There was also an increase in convergence of levels of perfectionism.
      The findings support the suggestion that social proximity promotes convergence of
      socially valued eating characteristics but divergence of socially stigmatised
      characteristics. Further research is suggested to establish the generalizability
      of these findings and to identify those who are most at risk of such social
      effects on eating disturbance.

PMID- 11225685
TI  - Childhood trauma and attempted suicide in alcoholics.

PMID- 11225686
TI  - Proactive coping among persons diagnosed with severe mental illness: an
      exploratory study.

PMID- 11225687
TI  - Compulsive buying severity: an analysis of Compulsive Buying Scale results in 44
      subjects.

PMID- 11225688
TI  - Fluvoxamine for psychosis in Alzheimer's disease.

PMID- 11225690
TI  - Evolution of depressive symptoms in human immunodeficiency virus-infected
      patients entering primary care.
AB  - Our purpose was to examine among HIV-infected patients a) characteristics
      associated with depressive symptoms at initial primary care presentation and b)
      factors associated with improvement in depressive symptoms. We interviewed HIV
      infected patients at initial presentation and reassessed them 6 months later. At
      baseline and follow-up, we collected data on depressive symptoms (CES-D) and
      other characteristics. Using multiple linear regression, we examined associations
      between CES-D score and baseline variables. We used multiple logistic regression
      to examine factors associated with improvement in depressive symptoms. Seventy
      one percent of the baseline sample (N = 203) scored above the threshold
      considered indicative of depression. At 6 months, 36% of the subjects who were
      followed improved in depressive symptoms. Higher baseline CES-D scores,
      improvements in HIV-related symptoms, and joining a support group were associated
      with improvement. Depressive symptoms in this urban HIV-infected population were
      highly prevalent. It is essential to screen, identify, and treat depression among
      patients entering care for HIV disease. Encouragement in joining support groups
      is a reasonable component of a strategy for addressing this common condition.

PMID- 11225691
TI  - Factors contributing to positive mood during the menopausal transition.
AB  - This study determined which variables affect women's positive mood state during
      the menopausal transition using nine prospective annual assessments of a
      population based sample of 267 Australian mid-aged women. Longitudinal data
      analysis carried out by analysis of covariance on Summary Statistics found that
      positive mood scores remained stable over time and were not related to natural
      menopausal transition, age, or education. In the early phase of the menopausal
      transition, positive mood was adversely influenced by baseline interpersonal
      stress (p = .009) and negative attitudes to aging (p = .026). The most important
      predictor of positive mood at the phase of late peri-/ postmenopause was positive
      mood in the premenopause (p = .000). Other factors affecting positive mood in the
      late peri-/postmenopause were changes in dysphoric symptoms (p = .000), major
      life events (p = .041), daily hassles (p = .014), marital status (p = .007), and
      work satisfaction (p = .001). Structural equation modelling found a goodness of
      fit index of .821.

PMID- 11225692
TI  - Applying social skills training in the context of vocational rehabilitation for
      people with schizophrenia.
AB  - This paper describes a model for the conceptualization of social skills necessary
      for the vocational success of people with schizophrenia. Based on this model, a
      two-part measure was developed and validated to assess social skills necessary
      for job search and tenure. The measure consists of a 10-item self-administered
      checklist and a role-play exercise. The self-administered checklist measures
      clients' perceived competence in handling work-related social situations. The
      role-play exercise assesses the social skills necessary for job acquisition and
      maintenance in two simulated situations (participating in a simulated job
      interview and requesting urgent leave from work). Furthermore, a social skills
      training module has been designed, which enhances vocational outcome and fills a
      gap in the existing, commonly used modules. A pilot study shows that the training
      module together with appropriate professional support afterward is effective in
      enhancing the social competence and vocational outcomes of persons with
      schizophrenia. Implications for cross-cultural applications are discussed.

PMID- 11225693
TI  - Combat trauma: trauma with highest risk of delayed onset and unresolved
      posttraumatic stress disorder symptoms, unemployment, and abuse among men.
AB  - Little is known about the risk and course of posttraumatic stress disorder
      (PTSD), and other forms of dysfunction, associated with combat trauma relative to
      other traumas. Modified versions of the DSM-III-R PTSD module from the Diagnostic
      Interview Schedule and Composite International Diagnostic Interview were
      administered to a representative national sample of 5,877 persons 15-54 years old
      in the part 2 subsample of the National Comorbidity Survey. Of the weighted
      subsample, 1,703 men reported a traumatic event. The risk of PTSD and other forms
      of dysfunction were compared for men who nominated combat as their worst trauma
      versus men nominating other traumas as worst, controlling for confounding
      influences. Men reporting combat as their worst trauma were more likely to have
      lifetime PTSD, delayed PTSD symptom onset, and unresolved PTSD symptoms, and to
      be unemployed, fired, divorced, and physically abusive to their spouses than men
      reporting other traumas as their worst experience.

PMID- 11225694
TI  - Chemical speciation used to assess [S,S']-ethylenediaminedisuccinic acid (EDDS)
      as a readily-biodegradable replacement for EDTA in radiochemical decontamination
      formulations.
AB  - Preliminary investigations into the replacement of widely used chelating agents
      for industrial cleansing of radionuclide contaminated items using readily
      biodegradable alternatives which have equivalent effectiveness, have been made
      using chemical speciation simulation programs and databases such as the JESS
      system. The chelation of radionuclide cations by [S,S']-EDDS has been compared
      with traditional decontamination agents, EDTA and citrate. Models indicate that
      in many respects, [S,S']-EDDS compares favourably with EDTA.

PMID- 11225695
TI  - Influence of glucose and urea on 125I transport across an anion exchange paper
      membrane.
AB  - In order to study the influence of glucose and urea on the 125I transport across
      an anion exchange paper membrane, the transmembrane potential, the fluxes, and
      the concentrations of 125I, glucose and urea within the membrane were measured in
      the Na125I concentration-cell system containing glucose or urea. Glucose and urea
      increased the membrane/solution distribution of the iodide ion, but scarcely
      affected the diffusion process of iodide ion within the membrane.

PMID- 11225696
TI  - Comparative study on sorption/desorption of radioeuropium on alumina, bentonite
      and red earth: effects of pH, ionic strength, fulvic acid, and iron oxides in red
      earth.
AB  - The sorption and desorption of Eu(III) as a representative of trivalent
      lanthanides and actinides on bentonite, alumina, red earth and red earth treated
      to remove free iron oxides were comparatively investigated by using batch
      technique and radiotracer 152 + 154Eu. The effects of pH, ionic strength, fulvic
      acid, iron oxides in red earth and the sorption mechanism were also discussed. As
      compared to alumina and red earth, Eu(III) presents a considerable distribution
      coefficient (Kd) onto bentonite. It was found that the pH and the presence of
      clay minerals are the main factors dominating the sorption/desorption
      characteristic of Eu3+ in the soil, and that a sorption-desorption hysteresis on
      bentonite and red earth actually occurs. Furthermore, the main sorption mechanism
      of lanthanides onto bentonite, alumina and red earth is the formation of bridged
      hydroxo complexes with the surface, and there are negative effects of fulvic acid
      and free iron oxides in red earth on the sorption of Eu(III). The results of this
      paper indicate that the additivity rule on the sorption characteristic of a soil
      from the individual component's characteristics is not general.

PMID- 11225697
TI  - Calibration of 32P "hot-wall" angioplasty-balloon-catheter sources by liquid
      scintillation-spectrometry-based destructive radionuclidic assays.
AB  - A very quantitative, destructive-analysis procedure was devised for assaying the
      32P activity content of "hot-wall" angioplasty-balloon catheters. These sources,
      developed and under investigation by Radiance Medical Systems, Inc. (Irvine, CA),
      are intended for use in the prophylactic inhibition of restenosis following
      balloon angioplasty in heart-disease patients. The assay was based on performing
      a physicochemical digestion of the balloon catheter to extract the 32P activity
      followed by liquid-scintillation (LS) spectrometry of the resultant solutions.
      Measurement-based corrections were applied for the residual activity remaining in
      the digested balloon debris and in all of the digestion apparatus. The LS
      spectrometry, with 3H-standard efficiency tracing, utilized a previously
      developed method for resolving the always-present 33P impurity. Initial
      ionization current measurements on the sources prior to the destructive assays
      led to the establishment of calibration factors that can be used for subsequent
      non-destructive radionuclidic measurements on similar balloon-catheter sources.

PMID- 11225698
TI  - The standardization of 177Lu by 4pibeta liquid scintillation spectrometry with 3H
      standard efficiency tracing.
AB  - Solutions containing the potential radiotherapy radionuclide 177Lu have been
      standardized at the National Institute of Standards and Technology (NIST) by
      4pibeta liquid scintillation (LS) counting with 3H-standard efficiency tracing
      using the CIEMAT/NIST method. Confirmatory measurements were made with 4pi
      NaI(TI) gamma-ray spectrometry. Activity determinations were made on 4 solutions
      over the course of 10 months with an expanded (k = 2) uncertainty on the activity
      of 0.8%. Half-life measurements were carried out using the NIST "4pi" gamma
      ionization chamber (IC) and LS counting and gave a new value of 6.65+/-0.01 d,
      which is shorter than the current ENSDF-recommended value by 1.3%. Impurity
      analyses were performed by high-purity germanium (HPGe) gamma-ray spectrometry
      and indicated only the presence of 177mLu at a level of 0.02% that of the 177Lu
      as of the respective reference times for the four solutions. Calibration factors
      for the NIST IC and Vinten 671 ionization chambers were developed, as were dial
      settings for the NIST-maintained Capintec CRC-12.

PMID- 11225699
TI  - Methylene blue-enhanced stability of (99mTc)HMPAO and simplified quality control-
      a comparative investigation.
AB  - (99mTc)HMPAO is a radiopharmaceutical used for SPECT imaging of regional cerebral
      perfusion and for labeling cellular blood elements. The addition of methylene
      blue enhanced the stability of lipophilic (99mTc)HMPAO complex up to 3 h after
      reconstitution, 86.9+/-4.2% compared to 49.8+/-8.9% for the non-stabilised
      complex and persists over time (86.2+/-3.5% after 15 min compared to 78.2+/-4.0%
      after 3 h). The method widely used for estimation of radiochemical purity is a
      standard chromatographic procedure which is quite time-consuming taking about 30
      min. Comparison of the more rapid and simple solvent extraction method with
      octanol, which needs only about 10 min to complete. showed a good correlation
      with the chromatographic method (84.4+/-4.4% compared to 89.1+/-4.3%). Using
      ethyl acetate as solvent instead of octanol gave a slightly higher extraction
      rate of the lipophilic complex (91.5+/-5.5% compared to 89.1+/-4.3%). Further,
      the ethyl acetate extraction method results in an overestimation, extracting
      partly secondary complex. It is confirmed, that the stability of the lipophilic
      (99mTc)HMPAO complex can be increased with methylene blue. The octanol extraction
      method, using higher extraction volume (up to 3 ml), is recommended as a fast and
      efficient approach for the quality control in daily clinical routine.

PMID- 11225700
TI  - Ligand-exchange reaction of labile "3 + 1"99mTc(V) complexes with SH group
      containing proteins.
AB  - The reactivity of labile 3 + 1 mixed-ligand 99mTc complexes of the type
      [99mTcO(SES)(RS)] with SES being a tridentate dithiol ligand and glutathione or
      dimethylcysteamine as monodentate ligands RSH towards proteins was investigated
      in vitro and in vivo. It was found that the complexes undergo reversible
      transchelation reactions with SH group-containing components of blood such as
      albumin or haemoglobin. High labelling yields were obtained when 3 + 1 complexes
      with the tridentate SSS ligand were used. The biodistribution of blood proteins
      labelled by ligand-exchange reaction with the [99TcO(SSS)] or [99mTcO(SNMeS)]
      core was studied and compared with the in vivo distribution of the labile 3 + 1
      complexes containing glutathione as monodentate ligand.

PMID- 11225701
TI  - Gross-alpha and gross-beta activities in airborne particulate samples. Analysis
      and prediction models.
AB  - Measurements of gross-alpha and gross-beta activities were made every week during
      the years 1992-1997 for airborne particulate samples collected using air filters
      at a clear site. The data are sufficiently numerous to allow the examination of
      variations in time and by these measurements to establish several features that
      should be important in understanding any trends of atmospheric radioactivity. Two
      models were used to predict the gross-alpha and gross-beta activities. A good
      agreement between the results of these models and the measurements was
      highlighted.

PMID- 11225702
TI  - Cross sections of (n,p), (n,alpha) and (n,2n) reactions on some isotopes of
      zirconium in the neutron energy range of 10-12 MeV and integral tests of
      differential cross section data using a 14 MeV d(Be) neutron spectrum.
AB  - Cross sections were measured for the 90Zr(n,alpha)87mSr, 90Zr(n,2n)89m,gZr,
      91Zr(n,p)91mY, 92Zr(n,p)92Y, 94Zr(n,alpha)91Sr and 96Zr(n,2n)95Zr reactions over
      the neutron energy range of 11.4 to 12.4 MeV and for the 94Zr(n,p)94Y reaction
      from 9.2 to 12.4 MeV. Nuclear model calculations were performed up to 16MeV. The
      statistical model incorporating precompound effects reproduces excitation
      functions of the three major threshold reactions, namely (n,p), (n,alpha) and
      (n,2n), quite well. Spectrum averaged cross sections were measured using a thick
      target Be(d,n) neutron field at Ed = 14 MeV. For the same neutron field averaged
      reaction cross sections were deduced using the excitation functions measured in
      this work as well as those given in the ENDF/B-VI, JEF-2, JENDL-3.2, BROND and
      ADL-3 data files. A comparison of the experimental and deduced integral data
      helped validating the differential data.

PMID- 11225703
TI  - Dose estimates to the public from 210Po ingestion via dietary sources at
      Kalpakkam (India).
AB  - Distribution of one of the natural radionuclides 210Po activity in food of plant
      origin such as cereals, pulses, vegetables and food of animal origin such fish,
      crab, prawn, chicken, egg etc. were determined in and around Kalpakkam upto a
      distance of 32 km radius. The general range of 210Po activity levels in all the
      dietary components (excluding milk and drinking water which are reported in mBq
      l(-1)) ranged widely from < or = 10 to 122,641 mBq kg(-1) fresh, the minimum
      being in vegetables and maximum being in the edible portions (muscle) of crab
      samples. 210Po levels in drinking water and milk samples ranged between 0.6-2.6
      and 8-12 mBq l(-1) respectively. 210Po content in cereals ranged from < or = 32
      to 745 mBq kg(-1) and in pulses it was found to vary between < or =32 and 294 mBq
      kg(-1). The range of 210Po activity in different types of vegetables was found to
      be < or = 10-653 mBq kg(-1). Among the different varieties of vegetables, 210Po
      was significantly higher in leafy vegetables (28-653 mBq kg(-1)) as compared to
      rooty and other types of vegetables which ranged from < or = 10-180 mBq kg(-1).
      In food of animal origin, the observed minimum activity of 210Po was 8 mBq l(-1)
      in milk and the maximum observed was 122,641 mBq kg(-1) in the muscles of crab.
      It was also observed that 210Po activity was found to be in higher levels in the
      food of aquatic animal origin (1414-122,641 mBq kg(-1)) than in the food of
      terrestrial animal origin (other than milk) which varied from 41 to 963 mBq kg(
      1). It is evident from the present study that the foods of animal origin
      especially crab, fish and prawn deliver significantly greater dose (93-3364
      microSv yr(-1)) to the public compared to foods of plant origin whose mean dose
      ranged 0.08-128 microSv yr(-1). The study showed evidence to suggest that the
      total ingestion dose due to 210Po received by the Kalpakkam public through
      dietary sources is significantly higher than the ingestion dose received due to
      fallout sources such as 137Cs and 90Sr.

PMID- 11225704
TI  - Development of a personal dosimetry system based on optically stimulated
      luminescence of alpha-Al2O3:C for mixed radiation fields.
AB  - To develop a personal optically stimulated luminescence (OSL) dosimetry system
      for mixed radiation fields using alpha-Al2O3:C, a discriminating badge filter
      system was designed by taking advantage of its optically stimulable properties
      and energy dependencies. This was done by designing a multi-element badge system
      for powder layered alpha-Al2O3:C material and an optical reader system based on
      high-intensity blue light-emitting diode (LED). The design of the multielement
      OSL dosimeter badge system developed allows the measurement of a personal dose
      equivalent value Hp(d) in mixed radiation fields of beta and gamma. Dosimetric
      properties of the personal OSL dosimeter badge system investigated here were the
      dose response, energy response and multi-readability. Based on the computational
      simulations and experiments of the proposed dosimeter design, it was demonstrated
      that a multi-element dosimeter system with an OSL technology based on alpha
      Al2O3:C is suitable to obtain personal dose equivalent information in mixed
      radiation fields.

PMID- 11225706
TI  - One approach for doublet deconvolution to improve reliability in spectra analysis
      for in vivo lead measurement.
AB  - Calculation of lead concentration from K-series X-ray fluorescent studies uses a
      robust normalization technique based on the amplitude or area of the elastic
      signal. Parameter estimation of the elastic signal can be affected by the overlap
      of the Kbeta2 line, especially for concentrations greater than 40 ppm where the
      Kbeta2 amplitude can be greater than 1% of the elastic signal. We tested the
      combination of estimation by method of least moduli and doublet deconvolution. We
      found that the estimation of the area of the elastic signal is more robust to
      changes in the low-energy end of the region of interest with the combined method
      than with method of least-squares estimation and singlet processing. We recommend
      use of the combined method for creation of calibration curves at concentrations
      greater than or equal to 40 ppm.

PMID- 11225705
TI  - Natural radioactivity in Algerian building materials.
AB  - Samples of natural and manufactured building materials collected from Algiers
      have been analysed for 226Ra, 232Th and 40K using a high-resolution HPGe gamma
      spectrometry system. The specific concentrations for 226Ra, 232Th and 40K, from
      the selected building materials, ranged from (12-65 Bq kg(-1)), (7-51 B qkg(-1))
      and (36-675 Bq kg(-1)), respectively. The measured activity concentrations for
      these natural radionuclides were compared with the reported data of other
      countries and with the world average activity of soil. Radium-equivalent
      activities were calculated for the measured samples to assess the radiation
      hazards arising from using those materials in the construction of dwellings. All
      building materials showed Ra(eq) activities lower than the limit set in the OECD
      report (370 Bq kg(-1)), equivalent to external gamma-dose of 1.5 mSv yr(-1).

PMID- 11225707
TI  - Precise emission probabilities of gamma-rays of 159Gd.
AB  - Measurement of emission probabilities for principal gamma-rays of 159Gd with
      4pibeta(ppc)-gamma(HPGe) coincidence apparatus has given precise values as
      indicated by uncertainties of about 1%. Improved certainties are seen when
      comparing the present results with emission probabilities evaluated in Nuclear
      Data Sheets (Helmer, 1994, p. 72) for which the uncertainties are about 24%. The
      improvement resulted in precise decay scheme parameters of the nuclide.

PMID- 11225708
TI  - Seasonal variation of air kerma in the "Vulcano Porto" area (Aeolian Islands,
      Italy).
AB  - Air kerma was measured in the "Vulcano Porto" area of the Vulcano Island,
      belonging to the Aeolian Islands, in the Mediterranean Sea. Measurements were
      carried out using thermoluminescence dosimeters. The relationship between
      observed dose values and source lithology has been assessed. Data show a seasonal
      variation due to weather conditions but also probably related to features of the
      soils, making the variation more evident.

PMID- 11225709
TI  - Body mass index and the prevalence of hypertension and dyslipidemia.
AB  - OBJECTIVE: To describe and evaluate relationships between body mass index (BMI)
      and blood pressure, cholesterol, high-density lipoprotein-cholesterol (HDL-C),
      and hypertension and dyslipidemia. RESEARCH METHODS AND PROCEDURES: A national
      survey of adults in the United States that included measurement of height,
      weight, blood pressure, and lipids (National Health and Nutrition Examination
      Survey III 1988-1994). Crude age-adjusted, age-specific means and proportions,
      and multivariate odds ratios that quantify the association between hypertension
      or dyslipidemia and BMI, controlling for race/ethnicity, education, and smoking
      habits are presented. RESULTS: More than one-half of the adult population is
      overweight (BMI of 25 to 29.9) or obese (BMI of > or =30). The prevalence of high
      blood pressure and mean levels of systolic and diastolic blood pressure increased
      as BMI increased at ages younger than 60 years. The prevalence of high blood
      cholesterol and mean levels of cholesterol were higher at BMI levels over 25
      rather than below 25 but did not increase consistently with increasing BMI above
      25. Rates of low HDL-C increased and mean levels of HDL-C decreased as levels of
      BMI increased. The associations of BMI with high blood pressure and abnormal
      lipids were statistically significant after controlling for age, race or
      ethnicity, education, and smoking; odds ratios were highest at ages 20 to 39 but
      most trends were apparent at older ages. Within BMI categories, hypertension was
      more prevalent and HDL-C levels were higher in black than white or Mexican
      American men and women. DISCUSSION: These data quantify the strong associations
      of BMI with hypertension and abnormal lipids. They are consistent with the
      national emphasis on prevention and control of overweight and obesity and
      indicate that blood pressure and cholesterol measurement and control are
      especially important for overweight and obese people.

PMID- 11225710
TI  - Differences in body fat and central adiposity between Swedes and European
      immigrants: the Malmo Diet and Cancer Study.
AB  - OBJECTIVE: Comparative data on ecological differences in body fatness and fat
      distribution within Europe are sparse. Migration studies may provide information
      on the impact of environmental factors on body size in different populations. The
      objective was to investigate differences in adiposity between European immigrants
      and native Swedes, specifically to examine gender differences and the effect of
      time since immigration, and to compare two selected immigrant groups with their
      native countrymen. RESEARCH METHODS AND PROCEDURES: A cross-sectional analysis of
      27,808 adults aged 45 to 73 years participating in the Malmo Diet and Cancer
      prospective cohort study in Sweden was performed. Percentage body fat (impedance
      analysis) and waist-hip ratio (WHR) were compared between Swedish-born and
      foreign-born participants. RESULTS: Obesity was 40% more prevalent in non-Swedish
      Europeans compared with Swedes. Controlling for age, height, smoking, physical
      activity, and occupation, it was found that women born in the former Yugoslavia,
      southern Europe, Hungary, and Finland had a significantly higher percentage of
      body fat, and those from Hungary, Poland, and Germany had more centralized
      adiposity compared with Swedish women. Men born in the former Yugoslavia,
      Hungary, and Denmark had a significantly higher mean percentage of body fat
      compared with Swedish-born men, whereas Yugoslavian, Finnish, and German men
      differed significantly in mean WHR. Length of residence in Sweden was inversely
      associated with central adiposity in immigrants. A comparison between German and
      Danish immigrants, their respective native populations, and Swedes indicated an
      intermediate positioning of German immigrants with regard to body mass index and
      WHR. DISCUSSION: Differences in general and central adiposity by country of
      origin appear to remain after migration. Central adiposity seems to be more
      influenced than fatness per se by time of residency in Sweden.

PMID- 11225711
TI  - Relationship of 30-year changes in obesity to sleep-disordered breathing in the
      Western Collaborative Group Study.
AB  - OBJECTIVE: Obesity is an important etiologic factor in sleep-disordered breathing
      (SDB), but the extent to which changes in obesity across adult life contribute
      independently to SDB in old age has not been studied. In this study, we examined
      the association between changes in obesity from midlife to late adulthood and
      overnight recording of respiration during sleep. RESEARCH METHODS AND PROCEDURES:
      Subjects in this study are from the Western Collaborative Group Study, a
      longitudinal cardiovascular epidemiological study that began in 1960 through
      1961. Overnight sleep recordings were obtained from 281 male participants in the
      1995 through 1996 follow-up of the Western Collaborative Group Study. Subjects
      were 75 to 91 years old when assessed for SDB as indexed by the respiratory
      disturbance index and an oxygen desaturation index (O2DI). Long-term changes in
      anthropometrics were evaluated and examined in relation to SDB severity. RESULTS:
      Over the 30 years of follow-up, body mass index and waist circumference increased
      significantly for this sample and were associated with SDB severity as indexed by
      respiratory disturbance index and O2DI. Waist circumference at baseline and gain
      in waist circumference over the 30 years of follow-up (both p = 0.01) were
      significantly and independently associated with SDB severity as assessed by O2DI.
      However, percentage of variance as accounted for by waist circumference was
      modest. DISCUSSION: This study supports the hypothesis that gain in waist
      circumference over adult life is significantly associated with SDB severity in
      older men.

PMID- 11225712
TI  - On the relation of attempting to lose weight, restraint, and binge eating in
      outpatients with binge eating disorder.
AB  - OBJECTIVE: To examine the relationship among attempts to lose weight, restraint,
      and eating behavior in outpatients with binge eating disorder (BED). RESEARCH
      METHODS AND PROCEDURES: Participants were 93 consecutive outpatients evaluated
      for a clinical trial who met Diagnostic and Statistical Manual, Fourth edition
      criteria for BED. The Eating Disorder Examination Interview was administered to
      assess attempts at weight loss, restraint, different forms of overeating, and the
      attitudinal psychopathology of eating disorders (i.e., concerns regarding eating,
      shape, and weight). In addition, the Three-Factor Eating Questionnaire was used
      to assess cognitive restraint, hunger, and disinhibition. Psychometrically
      established measures were given to assess body dissatisfaction, depression, and
      self-esteem. RESULTS: The majority of participants (75.3%; N = 70) reported
      attempting to lose weight, but only 37.6% (N = 35) reported dietary restraint on
      at least half the days of the month. Dietary restraint and cognitive restraint
      were not associated with any form of binge eating or overeating. Dietary
      restraint and cognitive restraint were positively correlated with weight concern,
      shape concern, and body dissatisfaction, and negatively correlated with body mass
      index. To further examine the interplay between attempting to lose weight and
      restraint, three study groups were created: unrestrained nonattempters (21.5%, N
      = 20), unrestrained attempters (40.9%; N = 38), and restrained attempters (34.4%;
      N = 32). The three groups did not differ significantly on binge eating or other
      eating behaviors; however, significant differences were observed for weight
      concern, shape concern, and body dissatisfaction. DISCUSSION: Attempts to lose
      weight and restraint are not synonymous for patients with BED. Although 75.3% of
      BED patients reported that they were attempting to lose weight, only 37.6%
      reported dietary restraint on at least half the days of the previous month. While
      restraint was negatively associated with body mass index, it was not related to
      binge eating or overeating. Our findings raise questions about prevailing models
      that posit restraint as a predominant factor in the maintenance of binge eating
      in BED.

PMID- 11225713
TI  - Expressions of leptin and insulin-like growth factor-I are highly correlated and
      region-specific in adipose tissue of growing rats.
AB  - OBJECTIVE: Anatomically distinct adipose tissue regions differ in their
      predominant modality of growth (i.e., cellular hypertrophy vs. hyperplasia). We
      examined site-specific patterns of expression of two genes whose products, leptin
      and insulin-like growth factor-I (IGF-I), could be involved in mediating
      differential growth and metabolism of white adipose tissue. We also related these
      patterns of expression to measures of adipose depot cellularity. RESEARCH METHODS
      AND PROCEDURES: Male Wistar rats were fed ad libitum and studied from ages 7
      weeks to approximately 12 months. Terminal measures of body weights; weights,
      composition, and cellularity of four white adipose depots; circulating leptin and
      IGF-I; and adipose depot-specific expression levels of leptin and IGF-I were
      measured in subsets of rats at 7, 12, 22, 42, and 46 weeks of age. RESULTS: Both
      leptin and IGF-I mRNAs are quantitatively expressed in a depot-specific manner,
      in the following order: retroperitoneal approximately equals epididymal >
      mesenteric > subcutaneous inguinal. Furthermore, there is a marked correlation
      between the expressions of these hormones in the various regions of adipose
      tissue of rats during the first year of life. The mechanisms that underlie the
      parallel expressions of leptin and IGF-I appear to be related to fat-cell volume.
      DISCUSSION: Because both leptin and IGF-I have been implicated in the regulation
      of energy homeostasis and are both expressed in adipose tissue, the depot
      specific linkage between the two genes suggests interaction at the autocrine
      level. This interaction may have an important role in determining functional
      properties particular to individual adipose depots.

PMID- 11225714
TI  - Topiramate reduces energy and fat gains in lean (Fa/?) and obese (fa/fa) Zucker
      rats.
AB  - OBJECTIVE: This study examined the effects of topiramate (TPM), a novel
      neurotherapeutic agent reported to reduce body weight in humans, on the
      components of energy balance in female Zucker rats. RESEARCH METHODS AND
      PROCEDURES: A 2 x 3 factorial experiment was performed in which two cohorts of
      Zucker rats differing in their phenotype (phenotype: lean, Fa/?; obese, fa/fa)
      were each divided into three groups defined by the dose of TPM administered
      (dose: TPM 0, vehicle; TPM 15, 15 mg/kg; TPM 60, 60 mg/kg). RESULTS: The
      reduction in body weight gain induced by TPM in both lean and obese rats
      reflected a decrease in total body energy gain, which was more evident in obese
      than in lean rats. Whereas TPM administration did not influence the intake of
      digestible energy in lean rats, it induced a reduction in food intake in obese
      animals. In lean, but not in obese rats, apparent energy expenditure (as
      calculated by the difference between energy intake and energy gain) was higher in
      rats treated with TPM than in animals administered the vehicle. The low dose of
      TPM decreased fat gain (with emphasis on subcutaneous fat) without affecting
      protein gain, whereas the high dose of the drug induced a reduction in both fat
      and protein gains. The effects of TPM on muscle and fat depot weights were
      representative of the global effects of TPM on whole body fat and protein gains.
      The calculated energetic efficiency (energy gain/energy intake) was decreased in
      both lean and obese rats after TPM treatment. TPM dose independently reduced
      hyperinsulinemia of obese rats, but it did not alter insulinemia of lean animals.
      DISCUSSION: The present results provide sound evidence for the ability of TPM to
      reduce fat and energy gains through reducing energetic efficiency in both lean
      and obese Zucker rats.

PMID- 11225715
TI  - Enhancing effect of troglitazone on porcine adipocyte differentiation in primary
      culture: a comparison with dexamethasone.
AB  - OBJECTIVE: This study compares the effects of the thiazolidinedione, troglitazone
      (TGZ), dexamethasone (DEX), and DEX plus TGZ on preadipocyte differentiation and
      the expression of CCAAT/enhancer-binding protein-alpha (C/ EBPalpha) and
      peroxisome proliferator-activated receptor-gamma (PPARgamma). RESEARCH METHODS
      AND PROCEDURES: Adipose tissue was obtained from postnatal pigs to isolate
      stromal-vascular cells. First, we applied 1, 5, or 10 microM TGZ and 10% fetal
      bovine serum for 3 days and counted the number of recruited preadipocytes. Next,
      we used either 10 microM TGZ, 80 nM DEX, or DEX plus TGZ with 10% fetal bovine
      serum for 3 days and then switched to serum-free medium with insulin for 6 days.
      On day 3 of culture, we counted preadipocytes, and on days 3 and 6 of culture, we
      performed immunostaining and Western blot analysis to determine the expression of
      C/EBPalpha and PPARgamma proteins. On day 9 of culture, we stained for lipids
      with oil red-O and measured the activity of glycerol phosphate dehydrogenase.
      RESULTS: DEX and TGZ equally enhanced recruitment of preadipocytes and late
      differentiation, but these effects were not additive with DEX plus TGZ treatment.
      However, TGZ and DEX had a differential effect on morphogenesis; DEX-treated
      adipocytes were larger and organized in loose clusters, whereas TGZ-treated cells
      were smaller and formed compact clusters. Both agents increased C/EBPalpha
      expression but in a temporally distinct manner. DEX was a better inducer than
      TGZ, and its effect was early and temporary. However, treatment with either TGZ
      or DEX did not change PPARgamma protein expression as evaluated by a Western
      blotting, but immunocytochemistry showed a tendency for increased numbers of
      PPARgamma positive cells. DISCUSSION: TGZ and DEX equally enhance early and late
      adipocyte differentiation, possibly by using some common pathways for
      preadipocyte recruitment. The differential effect on morphogenesis implies a
      potential differential effect on the expression of extracellular matrix
      components. C/EBPalpha may be the critical transcription factor involved in TGZ-
      and DEX-induced adipogenesis.

PMID- 11225717
TI  - Obesity, overweight, hypertension, and high blood cholesterol: the importance of
      age.

PMID- 11225716
TI  - Raised interleukin-6 levels in obese patients.
AB  - OBJECTIVE: Obese patients demonstrate a variety of biochemical, metabolic, and
      pulmonary abnormalities. Inflammatory mediators such as tumor necrosis factor
      alpha and interleukin-6 (IL-6) may have a direct effect on glucose and lipid
      metabolism. Hypoxemia in itself induces release of IL-6. The aim of this study
      was to examine the relationship between IL-6 levels in healthy volunteers
      (control group) and three different groups of obese patients: patients without
      obstructive sleep apnea syndrome (OSAS), patients with OSAS, and patients with
      obesity hypoventilation syndrome (OHS) (daytime baseline oxygen saturation of
      <93%). RESEARCH METHODS AND PROCEDURES: We measured serum IL-6 levels in 25 obese
      patients (body mass index of >35 kg/m2) and 12 healthy women. RESULTS: The
      results demonstrate statistically significant differences in serum IL-6 levels
      between the control group (1.28 +/- 0.85 pg/mL) and obese patients without OSAS
      (7.69 +/- 5.06 pg/mL, p < 0.05) and with OSAS (5.58 +/- 0.37 pg/mL, p < 0.0005).
      In the patients with OHS, IL-6 concentrations were highest (43.13 +/- 24.27
      pg/mL). DISCUSSION: We conclude that serum IL-6 is increased in obese patients.
      The highest IL-6 levels were found in the patients with OHS.

PMID- 11225718
TI  - Environmental selection of antibiotic resistance genes.

PMID- 11225720
TI  - The effects of copper on the microbial community of a coral reef sponge.
AB  - Marine sponges often harbour communities of symbiotic microorganisms that fulfil
      necessary functions for the well-being of their hosts. Microbial communities
      associated with the sponge Rhopaloeides odorabile were used as bioindicators for
      sublethal cupric ion (Cu2+) stress. A combined strategy incorporating molecular,
      cultivation and electron microscopy techniques was adopted to monitor changes in
      microbial diversity. The total density of sponge-associated bacteria and counts
      of the predominant cultivated symbiont (alpha-proteobacterium strain NW001) were
      significantly reduced in response to Cu2+ concentrations of 1.7 microg l(-1) and
      above after 14 days of exposure. The number of operational taxonomic units (OTUs)
      detected by restriction fragment length polymorphism (RFLP) decreased by 64% in
      sponges exposed to 223 microg l(-1) Cu2+ for 48 h and by 46% in sponges exposed
      to 19.4 microg l(-1) Cu2+ for 14 days. Electron microscopy was used to identify
      17 predominant bacterial morphotypes, composing 47% of the total observed cells
      in control sponges. A reduction in the proportion of these morphotypes to 25% of
      observed cells was evident in sponges exposed to a Cu2+ concentration of 19.4
      microg l(-1). Although the abundance of most morphotypes decreased under Cu2+
      stress, three morphotypes were not reduced in numbers and a single morpho-type
      actually increased in abundance. Bacterial numbers, as detected using
      fluorescence in situ hybridization (FISH), decreased significantly after 48 h
      exposure to 19.4 microg l(-1) Cu2+. Archaea, which are normally prolific in R.
      odorabile, were not detected after exposure to a Cu2+ concentration of 19.4
      microg l(-1) for 14 days, indicating that many of the microorganisms associated
      with R. odorabile are sensitive to free copper. Sponges exposed to a Cu2+
      concentration of 223 microg l(-1) became highly necrosed after 48 h and
      accumulated 142 +/- 18 mg kg(-1) copper, whereas sponges exposed to 19.4 microg
      l(-1) Cu2+ accumulated 306 +/- 15 mg kg(-1) copper after 14 days without
      apoptosis or mortality. Not only do sponges have potential for monitoring
      elevated concentrations of heavy metals but also examining changes in their
      microbial symbionts is a novel and sensitive bioindicator for the assessment of
      pollution on important microbial communities.

PMID- 11225719
TI  - Bacterial and archaeal populations associated with freshwater ferromanganous
      micronodules and sediments.
AB  - Biology is believed to play a large role in the cycling of iron and manganese in
      many freshwater environments, but specific microbial groups indigenous to these
      systems have not been well characterized. To investigate the populations of
      Bacteria and Archaea associated with metal-rich sediments from Green Bay, WI, we
      extracted nucleic acids and analysed the phylogenetic relationships of cloned 16S
      rRNA genes. Because nucleic acids have not been routinely extracted from metal
      rich samples, we investigated the bias inherent in DNA extraction and gene
      amplification from pure MnO2 using defined populations of whole cells or naked
      DNA. From the sediments, we screened for manganese-oxidizing bacteria using
      indicator media and found three isolates that were capable of manganese
      oxidation. In the phylogenetic analysis of bacterial 16S rRNA gene clones, we
      found two groups related to known metal-oxidizing genera, Leptothrix of the beta
      Proteobacteria and Hyphomicrobium of the alpha-Proteobacteria, and a Fe(III)
      reducing group related to the Magnetospirillum genus of the alpha-Proteobacteria.
      Groups related to the metal-reducing delta-Proteobacteria constituted 22% of the
      gene clones. In addition, gene sequences from one group of methanogens and a
      group of Crenarchaeota, identified in the archaeal gene clone library, were
      related to those found previously in Lake Michigan sediments.

PMID- 11225721
TI  - Use of green fluorescent protein and luciferase biomarkers to monitor survival
      and activity of Arthrobacter chlorophenolicus A6 cells during degradation of 4
      chlorophenol in soil.
AB  - The recently isolated novel species Arthrobacter chlorophenolicus A6 is capable
      of growth on and degradation of high concentrations of 4-chlorophenol (up to 350
      microg ml(-1)) as the sole carbon and energy source. This strain shows promise
      for bioremediation of environmental sites contaminated with high levels of
      chlorophenols. In this study, green fluorescent protein (gfp) or luciferase (luc)
      genes were used as biomarkers for monitoring cell number and activity,
      respectively, during degradation of 4-chlorophenol by A. chlorophenolicus cells.
      The individual marked strains, Arthrobacter chlorophenolicus A6L (luc-tagged) and
      Arthrobacter chlorophenolicus A6G (gfp-tagged), were monitored during degradation
      of 250 microg ml(-1) 4-chlorophenol in pure culture and 175 microg g(-1) 4
      chlorophenol in soil microcosms. Both gene-tagged strains were capable of
      cleaning up the contaminated soil during 9 d incubation. During the
      bioremediation experiments, the luc-tagged cells were monitored using luminometry
      and the gfp-tagged cells using flow cytometry, in addition to selective plate
      counting for both strains. The cells remained at high population levels in the
      soil (evidenced by GFP-fluorescent cell counts) and the A. chlorophenolicus A6L
      population was metabolically active (evidenced by luciferase activity
      measurements). These results demonstrate that the Arthrobacter chlorophenolicus
      A6 inoculum is effective for cleaning-up soil containing high concentrations of 4
      chlorophenol.

PMID- 11225722
TI  - Effects of community composition and growth rate on aquifer biofilm bacteria and
      their susceptibility to betadine disinfection.
AB  - Biofilm formation and function was studied in mixed culture using 20 bacterial
      strains isolated from a karst aquifer. When co-cultured in a glucose-limited
      chemostat, Vogesella indigofera and Pseudomonas putida were the dominant
      planktonic and biofilm organisms respectively. Biofilm formation and resistance
      to the iodine disinfectant betadine were then studied with monoculture and binary
      cultures of V. indigofera and P. putida and a 20-strain community. Biofilm
      population size [measured as colony-forming units (CFU) cm(-2)] increased with
      increasing species diversity. Significantly larger populations formed at dilution
      rates (DRs) of 0.0083 h(-1) than at 0.033 h(-1). P. putida populations were
      higher and V. indigofera lower in binary than in monoculture biofilms, suggesting
      that P. putida outcompeted V. indigofera. In binary biofilms, V. indigofera, a
      betadine-resistant organism, enhanced the survival of P. putida, a betadine
      susceptible organism. In the 20-strain biofilms, this protective effect was not
      observed because of low concentrations of V. indigofera (< 1% of the total
      population), suggesting that resistant organisms contribute to overall biofilm
      disinfectant resistance. Growth at 0.033 h(-1) enhanced survival of V. indigofera
      biofilms against betadine. Although DR did influence survival of the other
      communities, its effects were neither consistent nor significant. All told,
      biofilm formation and betadine resistance are complex phenomena, influenced by
      community composition, growth rate and betadine concentration.

PMID- 11225723
TI  - Long-term compositional changes after transplant in a microbial mat
      cyanobacterial community revealed using a polyphasic approach.
AB  - Using a polyphasic approach that included microscopy, cultivation and 16S rRNA
      based cultivation-independent molecular fingerprinting, we compared the
      cyanobacterial composition of Solar Lake microbial mats and samples thereof
      transplanted and maintained in new settings for extended periods of time.
      Significant changes in community composition, with clear replacement of the
      dominant cyanobacterium, Microcoleus chthonoplastes, were detected in all cases.
      The most dramatic shifts occurred in a sample kept in the laboratory for 3 years,
      which resulted in dominance by an Oscillatoria-like cyanobacterium whose 16S rRNA
      closely matched that of a morphologically similar isolate from mats in Mexico.
      Transfer of Solar Lake mat to an artificial experimental pond with incubation
      under seminatural conditions resulted in an increase in cyanobacterial diversity.
      Judging from the molecular signatures, two novel, previously unrecognized and
      phylogenetically well-delimited cyanobacterial populations became dominant.
      Through cultivation, one population was shown to correspond to a filamentous, non
      heterocystous group of Cyanobacteria with very narrow trichomes (approximately
      equals 0.75-1.5 microm). The most dominant novel molecular signature, however,
      could not be identified by cultivation efforts or correlation with microscopy
      and, upon phylogenetic analyses, its 16S rRNA genes showed no particular close
      association to known cyanobacterial groups.

PMID- 11225724
TI  - Sulphate reduction and nitrogen fixation rates associated with roots, rhizomes
      and sediments from Zostera noltii and Spartina maritima meadows.
AB  - Sulphate reduction rates (SRR) and nitrogen fixation rates (NFR) associated with
      isolated roots, rhizomes and sediment from the rhizosphere of the marine
      macrophytes Zostera noltii and Spartina maritima, and the presence and
      distribution of Bacteria on the roots and rhizomes, were investigated. Between 1%
      and 3% of the surface area of the roots and rhizomes of both macrophytes were
      colonized by Bacteria. Bacteria on the surfaces of S. maritima roots and rhizomes
      were evenly distributed, while the distribution of Bacteria on Z. noltii roots
      and rhizomes was patchy. Root- and rhizome-associated SRR and NFR were always
      higher than rates in the bulk sediment. In particular, nitrogen fixation
      associated with the roots and rhizomes was 41-650-fold higher than in the bulk
      sediment. Despite the fact that sulphate reduction was elevated on roots and
      rhizomes compared with bulk sediment, the contribution of plant-associated
      sulphate reduction to overall sulphate reduction was small (< or =11%). In
      contrast, nitrogen fixation associated with the roots and rhizomes accounted for
      31% and 91% of the nitrogen fixed in the rhizosphere of Z. noltii and S. maritima
      respectively. In addition, plant-associated nitrogen fixation could supply 37
      1,613% of the nitrogen needed by the sulphate-reducing community. Sucrose
      stimulated nitrogen fixation and sulphate reduction significantly in the root and
      rhizome compartments of both macrophytes, but not in the bulk sediment.

PMID- 11225725
TI  - A novel haloarchaeal-related lineage is widely distributed in deep oceanic
      regions.
AB  - During our study of the 16S rRNA gene sequence-based archaeal diversity of a deep
      sea site located at a 3,000 m depth at the Antarctic Polar Front, we detected
      several phylotypes ascribed to already known Group II and III Euryarchaeota, and
      a cluster of distinct sequences that branched off at the base of haloarchaea. The
      position of this lineage (marine Group IV) was very robust using distance
      (neighbour-joining) and maximum-likelihood methods. Subsequently, we designed
      specific primers for the detection of this archaeal group in other marine
      environments using polymerase chain reaction amplification and sequence
      comparison. Group IV archaea were found in the Antarctic area (across a gradient
      from the Southern ocean to the South Atlantic), and also in North Atlantic and
      Mediterranean waters. In all oceanic locations, Group IV archaea were never
      detected in surface waters, but were vertically distributed in the deepest part
      of the water column.

PMID- 11225726
TI  - Environmental microbes and greenhouse gases.

PMID- 11225727
TI  - Targeting cysteine residues of human immunodeficiency virus type 1 protease by
      reactive free radical species.
AB  - Nitric oxide (NO) is a naturally occurring free radical with many functions. The
      oxidized form of NO, the nitrosonium ion, reacts with the thiol group of cysteine
      residues resulting in their modification to S-nitrosothiols. The human
      immunodeficiency virus type 1 (HIV-1) protease (HIV-PR) has two cysteine residues
      that are conserved amongst different viral isolates found in patients with
      acquired immunodeficiency syndrome (AIDS). In an active dimer, these residues are
      located near the surface of the protease. We have found that treatment of HIV-PR
      with different NO congeners results in loss of its proteolytic activity and
      simultaneous formation of S-nitrosothiols. Sodium nitroprusside inhibited HIV-PR
      up to 70% and S-nitroso-N-acetylpenicillamine completely inhibited the protease
      within 5 min of treatment. The pattern of inhibition by NO donors is comparable
      to its inhibition by N-acetyl pepstatin. Using electrospray ionization-mass
      spectrometry, we identified the modification of HIV-PR by NO as that of S
      nitrosation. Our findings point towards a possible role of NO in mediating
      resistance to HIV-1 infection.

PMID- 11225728
TI  - Hydrogen peroxide-induced activation of SAPK/JNK regulated by
      phosphatidylinositol 3-kinase in Chinese hamster V79 cells.
AB  - To clarify activation mechanisms of stress-activated protein kinase/C-Jun N
      terminal kinase (SAPK/JNK) during oxidative stress, the roles of
      phosphatidylinositol 3-kinase (PI 3-kinase), concentration of intracellular
      calcium ([Ca2+]i), and cyclic AMP-dependent kinase (PKA) in hydrogen peroxide
      (H2O2)-induced SAPK/JNK activation were examined in Chinese hamster V79 cells.
      SAPK/JNK was dose-dependently activated after H2O2 treatment (from 10 microM to 1
      mM), and a PI 3-kinase inhibitor (wortmaninn), intracellular calcium chelator
      (BAPTA-AM), and PKA activator (dibutyl cyclic AMP and forskolin) inhibited this
      activation. An increase in [Ca2+], was observed after treatment with H2O2.
      Immunoprecipitation revealed that a PI 3-kinase regulatory subunit, p85alpha, was
      associated with insulin receptor substance 1 (IRS-1) phosphorylated by H2O2
      treatment. Furthermore, the formation of this complex of p85alpha and phospho-IRS
      1 was abolished by the presence of BAPTA-AM but not forskolin. These results
      indicated that the PI 3-kinase activated through phosphorylation of IRS-1
      upstream of SAPK/JNK after H2O2 treatment of V79 cells and that [Ca2+]i was a
      regulation factor for phosphorylation of IRS-1.

PMID- 11225729
TI  - Homocysteine and alpha-lipoic acid regulate p44/42 MAP kinase phosphorylation in
      NIH/3T3 cells.
AB  - Biological thiols can regulate cell signal transduction. The effects of two
      biothiols, homocysteine (Hcy), a risk factor for cardiovascular disease, and
      alpha-lipoic acid (alphaLA), a therapeutic antioxidant, on p44/42 mitogen
      activated protein kinases (MAPK) phosphorylation were examined in NIH/3T3
      fibroblasts. Cells grown in serum-containing media had constitutive levels of
      MAPK phosphorylation as determined by Western blot analysis using the phospho
      specific MAPK antibody. Treatment of cells with 20 microM Hcy for 0-60 min
      resulted in a transient enhancement of MAPK phosphorylation. In contrast, 20
      microM alphaLA inhibited serum-mediated phosphorylation of MAPK. The differential
      effects of these two thiols are not due to their redox states as oxidized Hcy
      (Hcy thiolactone) enhanced MAPK phosphorylation. The effect of alphaLA appears to
      be serum-dependent because Hcy or alphaLA treatment of serum-deprived cells
      activated MAPK phosphorylation. Thus, alphaLA and Hcy can either induce common
      signal transduction pathways or differentially modulate MAPK phosphorylation,
      depending on the state of the cell. This relationship may be important to
      understand how some biothiols are associated with pathogenic events while others
      offer potential as therapeutic agents.

PMID- 11225730
TI  - The actin cytoskeleton reorganization induced by Rac1 requires the production of
      superoxide.
AB  - The small GTPase rac1 controls actin redistribution to membrane ruffles in
      fibroblasts and other cell types, as well as the activation of the NADPH oxidase
      in phagocytes. We explored the possibility that these two processes could be
      related. We used a replication-deficient adenoviral vector to overexpress the
      constitutively active form of rac1, racV12, in human and mouse aortic endothelial
      cells. We show here that, in addition to membrane ruffle formation, racV12
      induced an increase in the total amount of F-actin within endothelial cells.
      Concurrently, racV12-overexpressing cells produced significantly higher amounts
      of free radicals, as detected by the fluorescent probe 5-(and-6)-chloromethyl
      2',7'-dichloro-dihydrofluorescein diacetate, than cells infected with a control
      virus encoding the bacterial beta-galactosidase (Ad-betaGal). To assess the
      specific role of superoxide in racV12-induced actin reorganization, we co
      expressed the human enzyme Cu,Zn-superoxide dismutase (SOD), by means of another
      adenoviral vector construct. Overexpressed SOD reduced the concentration of
      superoxide detected in Ad-racV12-transfected cells and reversed the effects of Ad
      racV12 on the content of filamentous actin. MnTMPyP, an SOD mimetic, as well as
      the antioxidant N-acetyl cysteine, had similar effects, in that they reduced not
      only the free radicals production, but also ruffle formation and the
      concentration of F-actin within racV12-overexpressing endothelial cells. Our data
      support the hypothesis that superoxide is one of the important mediators acting
      downstream of rac1 on the pathway of actin cytoskeleton remodeling in endothelial
      cells.

PMID- 11225731
TI  - Inhibition of the insulin receptor kinase phosphorylation by nitric oxide:
      functional and structural aspects.
AB  - Previous studies on cultured skeletal muscle cells have indicated that the
      insulin-induced expression of GLUT4 transporter protein is inhibited by nitric
      oxide (NO). Therefore, we determined the effect of NO on the insulin-induced
      autophosphorylation of the insulin receptor kinase (IRK), i.e., the first step in
      the insulin-mediated signal transduction pathway. The experiments showed that the
      insulin-induced autophosphorylation of the insulin receptor beta-chain is
      strongly inhibited by the NO donors 1,1-diethyl-2-hydroxy-2-nitrosohydrazine (DEA
      NO) or S-nitroso-N-acetylpenicillamine (SNAP). The inhibitory effect was
      ameliorated in cells depleted of glutathione (GSH), suggesting the possibility
      that S-nitroso-glutathione may operate as an intermediate NO donor. Complementary
      experiments with different Cys --> Ala mutant proteins showed, surprisingly, that
      all mutant proteins were inhibited by DEA-NO. Three-dimensional models of the
      nonphosphorylated IR beta-chain nitrosylated at the accessible cysteine residues
      1056, 1138, 1234, or 1245 revealed that derivatization of any of these four
      cysteine residues leads essentially to the same structural changes of the IRK
      domain. These changes involve a movement of the amino-terminal lobe against the
      carboxy-terminal lobe in a direction opposite to the direction of the "lobe
      closure" that was previously proposed to facilitate the accessibility for ATP and
      the expression of catalytic activity. Our findings suggest that the occurrence of
      several functionally relevant cysteine residues in distinct regions of the IRK
      protein increases the probability of regulatory redox interactions and thus the
      redox sensitivity of the IRK.

PMID- 11225732
TI  - Redox-mediated gene therapies for environmental injury: approaches and concepts.
AB  - Cellular redox state has been increasingly recognized as a critical component of
      stress-induced cellular responses and disease. Inherent in these responses are
      reactive oxygen species (ROS), which inflict direct cellular damage in addition
      to acting as intracellular second messengers modulating signal transduction
      pathways. These intracellular highways of communication are critical in
      determining cell fates and whole-organ responses following environmental injury.
      Although gene therapy for inherited and acquired disorders has exploded in the
      last decade, the application of gene therapeutic approaches for transient
      pathologic conditions resulting from environmental stress is just beginning to be
      recognized. This review will summarize the theoretical and practical applications
      of gene therapy for the treatment of environmental injury by modulating redox
      activated cellular responses. Several approaches can be utilized to achieve this
      goal. These include the application of gene targeting to modulate the cellular
      redox state directly by expressing recombinant genes capable of degrading ROS at
      pathophysiologic important subcellular sites. The use of mitochondrial superoxide
      dismutase (MnSOD), which degrades superoxides arising from ischemia/reperfusion
      injury, is one example of this approach. MnSOD serves as a "garbage disposal" for
      potentially toxic ROS prior to cellular injury and the activation of signal
      transduction cascades important in whole-organ pathology and inflammation. In
      contrast, some ROS have been suggested to have beneficial effects on cellular
      responses following environmental injury. Hence, expressing the nitrogen oxygen
      synthetase gene (NOS) to enhance the levels of nitric oxide (NO.) and augment the
      beneficial effects of this compound has also been suggested as a useful redox
      modulating gene therapy approach. Lastly, indirect intervention in signal
      transduction pathways following environmental stress by expressing dominant
      inhibitory proteins of redox-activated signal transduction cascades has also been
      useful in modulating cellular responses to redox stress. Two such examples have
      utilized dominant inhibitory forms of the retinoblastoma gene product (Rb) and
      IkappaBalpha which prevent activation of cyclin-dependent protein kinases and NF
      kappaB, respectively. Ultimately, the most efficacious therapeutic approach or
      combination of approaches that alter the redox responsiveness of cells and organs
      to environmental injury will be determined through a comprehensive understanding
      of the relevant pathophysiologic processes.

PMID- 11225733
TI  - Novel mechanisms involved in superoxide anion radical-triggered Ca2+ release from
      cardiac sarcoplasmic reticulum linked to cyclic ADP-ribose stimulation.
AB  - It has been suggested that cyclic adenosine 5'-diphosphoribose (cADPR) directly
      activates the cardiac isoform of the ryanodine receptor (RyR)/Ca2+ release
      channel. We have previously shown that selective activation of RyR/Ca2+ release
      channel by superoxide anion radical (O2.-) is dependent of the presence of
      calmodulin and identified calmodulin as a functional mediator of O2.- -triggered
      Ca2+ release through the RyR/Ca2+ release channel of cardiac sarcoplasmic
      reticulum (SR). We now demonstrate that although the effect of O2.- on Ca2+
      efflux from RyR/Ca2+ release channel at higher concentrations ( >5 microM) is due
      to its ability to produce a loss in function of calmodulin thereby decreasing
      calmodulin inhibition, O2.- radicals at lower concentrations (<5 microM) may be
      able to stimulate Ca2+ release only in the presence of calmodulin from the SR via
      increased cADPR synthesis; it is also shown that cADPR is a modulator that can
      activate the Ca2+-release mechanism when it is in a sensitized state by the
      presence of calmodulin, possibly, at physiological concentration. In addition,
      the SR vesicles immediately upon addition of cADPR, but not NAD+, did exhibit
      Ca2+ efflux stimulation. When heart homogenate was incubated with O2.-,
      conversion of NAD+ into cADPR was stimulated; the reduction of homogenate Ca2+
      uptake (by increasing Ca2+ efflux through RyR/Ca2+ release channel) occurred.
      Thus O2.- radical is responsible for cADPR formation from NAD+ in the cellular
      environment outside of the SR of heart muscle. The results presented here provide
      the first evidence of a messenger role for O2.- radical in cADPR-mediated Ca2+
      mobilization in myocardium.

PMID- 11225734
TI  - Androgen-induced oxidative stress in human LNCaP prostate cancer cells is
      associated with multiple mitochondrial modifications.
AB  - We investigated the role of androgen-induced oxidative stress in prostate cancer
      using the androgen-responsive LNCaP human prostate cancer cell line exposed to a
      1-nM concentration of the synthetic androgen R1881 (which correlates with serum
      androgen levels). Such exposure, which decreases growth rate and increases
      oxidative stress in LNCaP cells, induced statistically significant mitochondrial
      changes. A 40% increase in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium
      bromide (MTT) reduction, indicative of mitochondrial dehydrogenase activity,
      occurred 24 hr after androgen treatment. This change preceded 50-110% increases,
      40-96 hr after R1881 exposure, in levels of cellular peroxides and hydroxyl
      radicals as measured by 2'7'-dicholorofluorescin diacetate (DCF) fluorescence. On
      the basis of electron microscopy measurements, R1881 treatment increased the area
      fraction of mitochondria per cell by approximately 100% at 72 hr. In agreement,
      mitochondrial mass at 96 hr, evaluated by the fluorescent dye nonyl acridine
      orange (NAO), was 80% higher in treated cells. R1881 exposure for 24 hr lowered
      the activities of electron transport system (ETS) complexes, I, II, and IV by 17
      27% and ATP levels by 50%. The ETS inhibitors, rotenone and antimycin A, lowered
      androgen-induced DCF fluorescence readings to control levels thereby suggesting
      ETS involvement in androgen-induced oxidant production. Addition of alpha
      tocopherol succinate abrogated R1881-induced elevations in MTT reduction. In sum,
      androgens may, directly or indirectly, contribute to oxidative stress in LNCaP
      cells by regulating mitochondrial number, activity, and oxidant production by
      mechanisms that are, at least in part, sensitive to an antioxidant.

PMID- 11225735
TI  - High expression of human 15-lipoxygenase induces NF-kappaB-mediated expression of
      vascular cell adhesion molecule 1, intercellular adhesion molecule 1, and T-cell
      adhesion on human endothelial cells.
AB  - Expression of 15-lipoxygenase (15-LO) is induced over 100-fold in early fatty
      streak lesions. 15-LO activity leads to the production of specific lipid
      hydroperoxides, which can have major effects on the expression of proinflammatory
      genes involved in atherogenesis. We have used retrovirus-mediated gene transfer
      to achieve stable high expression of 15-LO in human endothelial ECV304 cells.
      These cells were used to study the effects of 15-LO on the expression of vascular
      cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1),
      activation of nuclear factor kappa B (NF-kappaB), and T-cell adhesion on
      endothelial cells. NF-kappaB activation was greatly potentiated by increased 15
      LO activity in the stably transduced cells, and both VCAM-1 and ICAM-1 were
      significantly induced in these cells in response to tumor necrosis factor-alpha
      (TNF-alpha) and phorbol 12-myristate 13-acetate (PMA) stimulation, as studied by
      flow cytometry. The induction of ICAM-1 was sensitive to antioxidants in a dose
      dependent manner. The adherence of Jurkat T cells on the 15-LO-expressing
      endothelial cells was markedly induced after PMA stimulation. These results
      indicate that 15-LO activity may be involved in the early pathogenesis of
      atherosclerosis by inducing VCAM-1 and ICAM-1 expression and by increasing T-cell
      adhesion on the endothelium.

PMID- 11225736
TI  - Mitochondria mediate tumor necrosis factor-alpha/NF-kappaB signaling in skeletal
      muscle myotubes.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is implicated in muscle atrophy and
      weakness associated with a variety of chronic diseases. Recently, we reported
      that TNF-alpha directly induces muscle protein degradation in differentiated
      skeletal muscle myotubes, where it rapidly activates nuclear factor kappaB (NF
      kappaB). We also have found that protein loss induced by TNF-alpha is NF-kappaB
      dependent. In the present study, we analyzed the signaling pathway by which TNF
      alpha activates NF-kappaB in myotubes differentiated from C2C12 and rat primary
      myoblasts. We found that activation of NF-kappaB by TNF-alpha was blocked by
      rotenone or amytal, inhibitors of complex I of the mitochondrial respiratory
      chain. On the other hand, antimycin A, an inhibitor of complex III, enhanced TNF
      alpha activation of NK-kappaB. These results suggest a key role of mitochondria
      derived reactive oxygen species (ROS) in mediating NF-kappaB activation in
      muscle. In addition, we found that TNF-alpha stimulated protein kinase C (PKC)
      activity. However, other signal transduction mediators including ceramide, Ca2+,
      phospholipase A2 (PLA2), and nitric oxide (NO) do not appear to be involved in
      the activation of NF-kappaB.

PMID- 11225737
TI  - Child outcomes of nonabusive and customary physical punishment by parents: an
      updated literature review.
AB  - This article updates the only previous systematic literature review of child
      outcomes of nonabusive and customary physical punishment by parents. The outcomes
      differ by methodologic, child, and subcultural factors as well as by how the
      physical punishment was used. All six studies that used clinical samples
      (including four randomized clinical studies) and all three sequential-analysis
      studies found beneficial outcomes, such as reduced noncompliance and fighting,
      primarily when nonabusive spanking was used to back up milder disciplinary
      tactics in 2- to 6-year olds. Five of eight longitudinal studies that controlled
      for initial child misbehavior found predominantly detrimental outcomes of
      spanking. However, those detrimental outcomes were primarily due to overly
      frequent use of physical punishment. Furthermore, apparently detrimental outcomes
      have been found for every alternative disciplinary tactic when investigated with
      similar analyses. Such detrimental associations of frequent use of any
      disciplinary tactic may be due to residual confounding from initial child
      misbehavior. Specific findings suggest discriminations between effective and
      counterproductive physical punishment with young children. More research is
      needed to clarify the role of spanking and alternative disciplinary tactics in
      control system aspects of parental discipline.

PMID- 11225740
TI  - Family-based therapy for adolescent drug abuse: knowns and unknowns.
AB  - Family-based therapy is one of the most thoroughly studied treatments for
      adolescent drug abuse. Considerable empirical support exists for the efficacy of
      family-based therapy in curtailing adolescent drug use and cooccurring behavior
      problems. This article extends knowledge of the effects of family-based therapy
      for adolescent drug abuse by reviewing 16 controlled trials and 4 therapy process
      studies from a treatment development perspective. We articulate "knowns and
      unknowns" regarding the outcomes of treatment as well as the components,
      processes, mechanisms, moderators, and boundaries of effective family-based
      therapy for adolescent drug abuse. The review highlights areas of progress and
      future research needs within the specialty of family-based therapy for adolescent
      drug abuse.

PMID- 11225741
TI  - Implications of cardiovascular risk in patients with type 2 diabetes who have
      abnormal lipid profiles: is lower enough?
AB  - Patients with type 2 diabetes are at high risk for coronary heart disease (CHD);
      frequently, these patients have abnormal lipid profiles, placing them at even
      greater risk. A syndrome of insulin resistance, hyperinsulinaemia, hypertension,
      and high levels of fibrinogen and plasminogen activator inhibitor contributes to
      cardiovascular risk, which is not sufficiently decreased by glycaemic control
      alone. In several large interventional trials, CHD risk in patients with diabetes
      was substantially reduced by aggressive lipid-lowering therapy. In patients with
      diabetes, CHD, low high-density lipoprotein levels, and normal low-density
      lipoprotein levels, gemfibrozil reduced fatal and non-fatal CHD events. For lipid
      lowering in patients with diabetes and CHD, pravastatin and simvastatin are the
      only HMG-CoA reductase inhibitors shown to reduce fatal and non-fatal CHD events.
      Of these, pravastatin has less potential for drug-drug interactions and may be
      safer to use, particularly for combination therapy with fibric acid derivatives,
      as may now be important for CHD prevention in mixed dyslipidaemias.

PMID- 11225739
TI  - The efficacy, safety, and practicality of treatments for adolescents with
      attention-deficit/hyperactivity disorder (ADHD).
AB  - Studies examining interventions for adolescents diagnosed with attention
      deficit/hyperactivity disorder (ADHD) were reviewed to evaluate their efficacy.
      These efficacy findings were supplemented with a preliminary system for judging
      safety and practicality. Results suggest that the stimulant drug methylphenidate
      (MPH) is safe and well-established empirically, but has some problems with
      inconvenience and noncompliance. Preliminary research supports the efficacy,
      safety, and practicality of some psychotherapeutic interventions, including
      behavioral classroom interventions, note-taking training, and family therapy.
      Treatment with tricyclic antidepressants was judged to have minimal empirical
      support and debatable safety. Very little is known about long-term effectiveness
      of treatments, long-term compliance, or multimodal treatments for adolescents
      such as stimulants plus behavior therapy.

PMID- 11225742
TI  - Assessment of the effects of insulin secretagogues in humans.

PMID- 11225743
TI  - Insulin action in vascular endothelium: potential mechanisms linking insulin
      resistance with hypertension.

PMID- 11225738
TI  - School-based mental health services: a research review.
AB  - This paper provides a synthetic review of research on school-based mental health
      services. Schools play an increasingly important role in providing mental health
      services to children, yet most school-based programs being provided have no
      evidence to support their impact. A computerized search of references published
      between 1985 and 1999 was used to identify studies of school-based mental health
      services for children. Study inclusion was determined by (i) use of randomized,
      quasi-experimental, or multiple baseline research design; (ii) inclusion of a
      control group; (iii) use of standardized outcome measures; and (iv) baseline and
      postintervention outcome assessment. The application of these criteria yielded a
      final sample of 47 studies on which this review is based. Results suggest that
      there are a strong group of school-based mental health programs that have
      evidence of impact across a range of emotional and behavioral problems. However,
      there were no programs that specifically targeted particular clinical syndromes.
      Important features of the implementation process that increase the probability of
      service sustainability and maintenance were identified. These include (i)
      consistent program implementation; (ii) inclusion of parents, teachers, or peers;
      (iii) use of multiple modalities; (iv) integration of program content into
      general classroom curriculum; and (v) developmentally appropriate program
      components. Implications of these findings and directions for future research are
      discussed.

PMID- 11225745
TI  - Optimizing insulin delivery: assessment of three strategies in intensive diabetes
      management.
AB  - OBJECTIVE: To compare three intensive management strategies with respect to
      metabolic control (glycated haemoglobin, preprandial blood glucose, lipid
      profile, body weight, hypoglycaemic episodes) and psycho-social adaptation
      (quality of life, self-efficacy, stress and perceived complexity). RESEARCH
      DESIGN AND METHODS: Fifteen adults with type 1 diabetes completed this 1-year,
      randomized, prospective, cross-over study. The three treatment strategies were
      categorized according to flexibility with insulin self-adjustments as follows:
      Simplified (SIMP) = meal plan based on food exchanges with no self-adjustments of
      insulin for food, exercise and stress; Qualitative (QUAL) = meal plan based on
      food exchanges with qualitative adjustment of insulin for food, exercise and
      stress; Quantitative (QUANT) = meal plan using carbohydrate counting with
      quantitative adjustment of insulin for food and qualitative adjustment for
      exercise and stress. All three strategies allowed for adjustments of insulin for
      preprandial blood glucose and the option of adjusting diet for exercise. All
      subjects followed each strategy for 3.5 months. Subjects kept detailed log sheets
      where they recorded preprandial blood glucose, insulin dosages, food intake,
      activity and stress level at least four times/day. The psycho-social aspects were
      determined with validated questionnaires that were completed before and after
      each strategy. RESULTS: There were no statistically significant differences in
      metabolic control, quality of life and self-efficacy between the three
      strategies. The mean (+/- s.e.) for HbA1 levels (normal < 8.5%) were: Baseline:
      10.9+/-0.06 and End of SIMP = 9.7+/-0.03; QUAL = 9.5+/-0.04; QUANT = 10.2+/-0.04.
      Body weight and serum lipid levels did not change significantly. The frequency of
      severe hypoglycaemic episodes for the entire study was 20 episodes/100 patient
      years. Perceived complexity of treatment strategy increased (p < 0.0001) from
      SIMP to QUANT (least to most flexible). Although the majority of subjects (n =
      11) were following a strategy similar to SIMP prior to entering the study, 12
      subjects chose to continue with QUAL, three with QUANT and none with SIMP at the
      end of the study. CONCLUSIONS: These results indicate that a strategy that allows
      for flexibility of self-adjustments of insulin and is not very complex (such as
      QUAL) may be the strategy of choice for intensive management programmes.

PMID- 11225744
TI  - Plasma endothelin in postmenopausal women with type 2 diabetes mellitus and
      metabolic syndrome: a comparison of oral combined and transdermal oestrogen-only
      replacement therapy.
AB  - AIM: Type 2 diabetes and metabolic syndrome are major cardiovascular risk factors
      in postmenopausal women, but the role of vasoconstrictive endothelin-1 (ET-1) in
      these conditions is not known. We studied the levels of ET-1 and the effect of
      postmenopausal hormonal therapy on ET-1 levels in postmenopausal women. METHODS:
      We compared plasma levels of ET-1 in 22 postmenopausal type 2 diabetic women and
      14 postmenopausal women with metabolic syndrome with plasma levels in 10 healthy
      postmenopausal control women. The basal values for ET-1 were measured for all
      groups. These women were then randomised to receive in a double-dummy, crossover
      trial: either oral continuous oestradiol (2.0 mg) + norethisterone acetate (1.0
      mg) per day or continuous transdermal oestrogen-only (50 mg/day) for 3 months.
      Between the active therapy there were 3-month wash-out periods. ET-1-values were
      measured again at the end of each treatment period. RESULTS: The type 2 diabetic
      women had significantly (p < 0.003) elevated ET-1 levels (4.8+/-1.0 pg/ml)
      whereas those with metabolic syndrome (4.4+/-1.7 pg/ml]) had non-significantly
      (NS) elevated ET-1 levels compared to controls (3.6+/-0.3 pg/ml). Both oral and
      transdermal hormone replacement therapy (HRT) failed to affect plasma ET-1 except
      in 14 hypertensive women from the diabetes and metabolic syndrome groups who were
      on angiotensin convertase enzyme (ACE) inhibitors. These women's ET-1 levels
      before oral HRT (4.6+/-1.1 pg/ml) fell to 4.1+/-0.9 pg/ml (p < 0.05).
      CONCLUSIONS: Type 2 diabetes in postmenopausal women is associated with elevated
      ET-1 levels. Oestrogen replacement therapy does not affect the levels of ET-1 in
      postmenopausal women with type 2 diabetes or metabolic syndrome.

PMID- 11225747
TI  - Leptin concentrations are related to glycaemic control, but do not change with
      short-term oral antidiabetic therapy in female patients with type 2 diabetes
      mellitus.
AB  - This study evaluated the relation of leptin with glycaemic control and the effect
      of 14 days of diet, or diet combined with gliclazide, glipizide-GITS or metformin
      treatment, on leptin concentration in 51 female patients with type 2 diabetes
      mellitus. Leptin levels were similar both at baseline and after treatment in
      diabetic and control groups. Diabetic patients with basal fasting plasma glucose
      (FPG) < 10 mmol/l or with basal postprandial plasma glucose (PPPG) < 13.9 mmol/l
      had significantly higher leptin levels than diabetic patients with basal FPG > or
      = 10 mmol/l or with basal PPPG > or = 13.9 mmol/l (19.6+/-8.7 vs. 13.65+/-5.4
      microg/l, p < 0.05; and 20.2+/-7.9 vs. 12.9+/-5.2 microg/l, p < 0.05,
      respectively). Mode of treatment did not influence leptin levels. Delta leptin
      showed a weak correlation with basal FPG (r = 0.346; p < 0.05), basal and post
      treatment PPPG (r = 0.335, p < 0.05 and r = 0.325, p < 0.05, respectively) and a
      moderate correlation with post-treatment FPG (r = 0.391, p < 0.01). In
      conclusion, leptin level is not affected by the presence of type 2 diabetes
      mellitus and by short-term treatment with diet or oral antidiabetic drugs but is
      directly related to glycaemic control in female patients with type 2 diabetes
      mellitus.

PMID- 11225746
TI  - Impact of insulin lispro on HbA1c values in insulin pump users.
AB  - AIM: To compare the therapeutic efficacy of the short-acting insulin analogue
      insulin lispro (Humalog) with that of buffered regular human insulin (Velosulin)
      in patients on insulin pump therapy. PATIENTS AND METHODS: Sixty-two (45 women
      and 17 men) young patients with type 1 diabetes using insulin pump therapy were
      compared while using buffered regular human insulin for a mean +/- s.e.m. of
      20.1+/-1.2 months or insulin lispro for a mean +/- s.e.m. of 19.7+/-0.5 months.
      The initial mean +/- s.e.m. age and duration of diabetes were 29.1+/-0.9 and
      17.7+/-0.9 years, respectively. The mean HbA1c values, basal insulin dosages,
      premeal insulin dosages and number of low blood sugars were recorded during
      treatment with both insulins. RESULTS: Mean +/- s.e.m. HbA1c values were
      significantly lower (p < 0.001; paired Wilcoxon t-test) during insulin lispro
      treatment (7.4+/-0.1%) as compared to treatment with buffered regular human
      insulin (7.9+/-0.1%). Total units of insulin (mean +/- s.e.m.)/kg/day was
      significantly (p = 0.03) lower (0.61+/-0.02) during the insulin lispro treatment
      period as compared to the buffered regular human insulin treated period (0.65+/
      0.03). Total mean +/- s.e.m. (U/kg/day) of basal insulin administered per day was
      higher when patients received insulin lispro treatment (0.44+/-0.02 vs. 0.42+/
      0.01 for buffered regular human insulin treated period; p = 0.002). The premeal
      insulin boluses (mean +/- s.e.m.) for the two treatment groups were significantly
      different with less insulin required for the insulin lispro treatment period for
      all three meals (p < 0.001, t-test). The number of mild/moderate and severe
      hypoglycaemic episodes were similar in the two groups. CONCLUSION: We conclude
      that use of insulin lispro in pump therapy significantly lowers HbA1c values in
      comparison to therapy with buffered regular human insulin insulin without
      increasing hypoglycaemic episodes.

PMID- 11225748
TI  - Short-term hypothyroidism has no effect on serum leptin concentrations.
AB  - The aim of the study is to determine the effect of short-term hypothyroidism on
      serum leptin levels. For this purpose 30 patients with past medical history of
      thyroidectomy for differentiated thyroid carcinoma were included. Serum leptin
      concentrations were similar when patients were on thyrotrophin-suppressive
      thyroxine therapy than when were admitted 4 weeks after stopping thyroxine
      treatment to perform a routine 131I scan in hypothyroid status (17.0 +/- s.e.m.
      2.14 vs. 17.6 +/- s.e.m. 2.41 ng/ml; p = n.s.). Moreover, no differences were
      obtained when the analysis was performed separately in men and in women. We
      conclude that short-term hypothyroidism does not alter serum leptin
      concentrations. Furthermore, our results suggest that thyroid hormones do not
      operate through changes in serum leptin levels to regulate energy expenditure.

PMID- 11225749
TI  - Variations in plasma soluble tumour necrosis factor receptors after diet-induced
      weight loss in obesity.
AB  - The aim of this study was to investigate the variations in the plasma levels of
      the soluble tumour necrosis factor receptor type-I (sTNFR-I) and type-II (sTNFR
      II) during weight loss which was induced by 3 weeks on a very low calorie diet
      (3.9+/-0.1 MJ/day), in 17 non-diabetic obese women. Plasma sTNFR-I concentrations
      decreased significantly after weight loss (p < 0.05), but there was no
      significant change in plasma sTNFR-II. As the diet was associated with a
      significant decrease in body fat mass (=2.5 kg), this result supports the
      emerging concept that adipose tissue can produce significant amounts of sTNFR-I
      and that this production can be modified by weight loss in human obesity.

PMID- 11225750
TI  - Posttraumatic stress disorder in children and adolescents: a review and analysis.
AB  - Only recently has the mental health community recognized the applicability of
      diagnostic criteria for posttraumatic stress disorder (PTSD) in children and
      adolescents, including a consideration of specific age-related features. This
      paper provides a current review of the literature on PTSD pertaining to children
      and adolescents. Following a discussion of issues on diagnostic criteria and
      assessment of this affective disorder in this population, there is an overview of
      the existing literature on prevalence, comorbidity, risk factors, parental and
      family factors, and issues of gender and age of onset. The remainder of the paper
      focuses on the range of traumatic stressors in children and adolescents that can
      result in PTSD, including natural or human disasters, war and violence, chronic
      or life-threatening medical conditions, community violence and the witnessing of
      traumatic events, and physical and/ or sexual abuse and other forms of
      interpersonal violence. Throughout the paper, there is an emphasis on the
      importance of considering developmental factors. Finally, implications of the
      existing literature for future areas of research are addressed.

PMID- 11225751
TI  - A truly early starter model of antisocial behavior revisited.
AB  - This paper revisits a developmental model of the origins of early conduct
      problems. Several of the model's primary tenets have now been validated in two
      samples of at-risk children followed prospectively from infancy to school-age. In
      both cohorts, child, family, and sociodemographic factors all play a significant
      role in the development of early conduct problems. In particular, the quality of
      the caregiving environment during the child's second year differentiates clinical
      impairment according to both parent and teacher report 6 years later. We conclude
      by making recommendations for future studies. Research that utilizes a
      developmental framework, incorporates more sophisticated measurement of infant
      negative emotionality, and addresses the influences of neighborhood and culture,
      is suggested.

PMID- 11225752
TI  - The role of the family in childhood obsessive-compulsive disorder.
AB  - While obsessive-compulsive disorder is widely recognized to have a strong genetic
      component, psychosocial factors are also acknowledged to be important. The
      primary focus of this paper is on familial factors associated with OCD in
      children and adolescents. It explores the family context as a possible risk
      factor in the development and maintenance of the disorder, including parental
      modeling, expressed emotion, parenting style, and family accommodation of the
      child's symptoms. The involvement of the family in the treatment of the disorder
      is also reviewed. Finally, future directions for research investigating familial
      factors in childhood OCD are presented.

PMID- 11225753
TI  - Methodological issues in the direct observation of parent-child interaction: do
      observational findings reflect the natural behavior of participants?
AB  - This review examines evidence for the utility and validity of direct
      observational techniques for answering particular research and clinical
      questions. Observational techniques often involve recording behavior in settings
      that are relatively unnatural for families. However, it is argued that construct
      validity of observational methods depends partly on whether the findings are
      representative of participants' typical everyday behavior. Evidence is reviewed
      concerning whether observational findings are affected by the presence of the
      observer, and by two factors which have been neglected in the literature, namely
      the type of task imposed by the observer (e.g., directing parent and child to
      play rather than observing spontaneous interaction) and the location of the
      observations (e.g., clinic or laboratory rather than home). The review suggests
      that the presence of an observer does not necessarily distort the nature of
      interactions. However, the small number of studies in this area suggest that
      interactions in structured or artificial settings are not necessarily
      representative of those normally taking place at home.

PMID- 11225754
TI  - Postprandial glucose: the nondiabetic state.

PMID- 11225755
TI  - Postprandial hyperglycaemia: potential relationship to the development and
      progression of diabetic nephropathy.

PMID- 11225756
TI  - Type 2 diabetes and atherosclerosis.

PMID- 11225757
TI  - Diabetic dyslipidaemia.
AB  - Dyslipidaemia is an important component of the metabolic syndrome observed in
      patients with type 2 diabetes, and is characterized by moderate
      hypertriglyceridaemia and low levels of high-density lipoprotein (HDL)
      cholesterol concentrations. Dyslipidaemia contributes to increased vascular risk
      and is therefore a good target for therapeutic intervention in the form of
      glycaemic control, lifestyle measures and hypolipidaemic drugs. It is proposed
      that lipid abnormalities in type 2 diabetes are secondary consequences of insulin
      resistance. Any approach that lowers insulin resistance would be anticipated to
      have a beneficial effect on dyslipidaemia, but in many cases patients with type 2
      diabetes fail to achieve normal lipidaemia through diet, exercise and glycaemic
      control. Subgroup analyses of major clinical trials suggests that lipid-lowering
      therapy reduces CHD risk in patients with diabetes, but trials performed
      specifically in populations of patients with diabetes are ongoing. Until then,
      patients with type 2 diabetes who have established CHD or high individual risk
      already warrant aggressive lipid-lowering pharmacotherapy. In the author's view,
      when ongoing studies are complete it is likely that most patients with type 2
      diabetes will be prescribed lipid-lowering drugs.

PMID- 11225758
TI  - The impact of antihypertensive therapy in type 2 diabetes.

PMID- 11225759
TI  - Repaglinide: prandial glucose regulation in clinical practice.
AB  - Prandial glucose regulation represents a new concept in the management of type 2
      diabetes: targeting postprandial glycaemic excursions as a means of achieving
      long-term glycaemic control. Although control of the overall glycaemic load is
      the most important factor for the success of long-term management of type 2
      diabetes, control of postprandial hyperglycaemia also has positive implications
      for preventing the development of diabetic complications. Repaglinide is the
      first prandial glucose regulator to become available in the clinical setting. It
      has a rapid and short-lived insulinotropic action and can therefore reduce
      postprandial glucose excursions without increasing the risk of hypoglycaemia.
      Short-term clinical studies showed that repaglinide is superior to glibenclamide
      in improving postprandial glycaemic control. Longer-term studies confirmed that
      improved PGR is accompanied by improved overall glycaemic control that is at
      least equivalent to that achieved by sulphonylurea treatment. Moreover, because
      repaglinide can be used with flexible meal patterns without compromising glucose
      control, it can improve quality of life as indicated by overall treatment
      satisfaction, well-being and health status. Repaglinide has few contraindications
      or drug interactions and can be used in a wide range of patients. Although
      careful titration of repaglinide dose is recommended for patients with mild to
      moderate renal impairment, no dosage adjustment is otherwise needed in the
      elderly. In addition to being an effective first-line hypoglycaemic agent,
      repaglinide is highly effective in combination therapy for patients with type 2
      diabetes who require more intensive treatment. When glucose targets are not met
      using repaglinide monotherapy, the combination of repaglinide with metformin can
      further improve glycaemic control by enhancing insulin secretion and improving
      insulin sensitivity. Similarly, when required combination of repaglinide with
      troglitazone or NPH-insulin can produce better glycaemic control than monotherapy
      alone. Given that most patients with type 2 diabetes require a multitherapy
      approach to achieve and sustain adequate glycaemic control, repaglinide will be
      an important element in future intensive therapy regimens.

PMID- 11225760
TI  - Case presentations--challenging problems in the management of type 2 diabetes.

PMID- 11225761
TI  - Postprandial hyperglycaemia: mechanisms and importance.

PMID- 11225762
TI  - Prandial glucose regulation in context. Proceedings of a workshop. 15-17 January
      1999, Granada, Spain.

PMID- 11225763
TI  - Outlook on bioanalysis.

PMID- 11225764
TI  - Proteomics. Concepts and perspectives.
AB  - Within the last five years the field of proteomics has changed the understanding
      of molecular biology. Proteins manifest physiological as well as
      pathophysiological processes in a cell or an organism, and proteomics describes
      the complete protein inventory in dependence on in vivo parameters. Disease
      mechanism or drug effects both affect a protein profile and, vice versa,
      characterising protein profiles reveals information for the understanding of
      disease and therapy. Analytical methods for proteomics are based on conventional
      tools for protein characterisation. The technical challenge is the complete
      coverage of physico-chemical properties for thousands of proteins. Nucleic acids
      display a relative chemical homogeneity and therefore genomics was considered
      more promising in the past than proteomics. Further improvements in proteomics
      technologies will likely change this course with proteomics complementing
      genomics as a tool to study life sciences.

PMID- 11225765
TI  - Miniaturized total analysis systems for biological analysis.
AB  - This review article discusses and documents the basic philosophies, concepts and
      current advances in the field of micro-TAS development, with special emphasis on
      applications in the arena of biosciences. After a brief overview of
      miniaturization theory and fabrication techniques, areas of microfluidic
      component development, detection protocols, biochemical assays, and integrated
      biological analyses are addressed.

PMID- 11225766
TI  - Biosensors and biochips: advances in biological and medical diagnostics.
AB  - In the past two decades, the biological and medical fields have seen great
      advances in the development of biosensors and biochips capable of characterizing
      and quantifying biomolecules. This review is meant to provide an overview of the
      various types of biosensors and biochips that have been developed for biological
      and medical applications, along with significant advances over the last several
      years in these technologies. It also attempts to describe various classification
      schemes that can be used for categorizing the different biosensors and provide
      relevant examples of these classification schemes from recent literature.

PMID- 11225767
TI  - Cell-based biosensors.
AB  - Different classes of cell-based biosensors are introduced. These include devices
      to measure cell-cell contact and set-ups to determine metabolic products. Main
      emphasis is put on sensors based on nerve-cell networks which are able to detect
      neuro-active compounds. The different experimental set-ups are explained and
      examples for typical applications are given. A main point concerns new
      achievements and prospects for future developments.

PMID- 11225768
TI  - Electron-transfer mechanisms in amperometric biosensors.
AB  - The function of amperometric biosensors is related to electron-transfer processes
      between the active site of an (immobilized) enzyme and an electrode surface which
      is poised to an appropriate working potential. Problems and specific features of
      architectures for amperometric biosensors using different electron-transfer
      pathways such as mediated electron transfer, electron-hopping in redox polymers,
      electron transfer using mediator-modified enzymes and carbon-paste electrodes,
      direct electron transfer by means of self-assembled monolayers or via conducting
      polymer chains are discussed.

PMID- 11225769
TI  - Nanoscale fluorescent sensors for intracellular analysis.
AB  - There is a growing interest in the development of submicron optochemical sensing
      devices. Miniaturization of sensors to nano-dimensions decreases their typical
      response time down to the millisecond time scale. Their penetration volume is
      reduced to a few cubic micrometers and they exhibit a spatial resolution at the
      nanometer scale. In this review the fabrication of submicron optical fiber
      fluorescent sensors and particle-based fluorescent nanosensors is described. The
      functional characteristics of these exciting miniaturized fluorescent sensors and
      their applications for quantitative measurement of intracellular analytes are
      demonstrated.

PMID- 11225770
TI  - Label-free detection of biomolecular interaction by optical sensors.
AB  - Since the first label-free optical biosensor was commercialized in 1990 a rising
      number of publications have demonstrated the benefits of direct biomolecular
      interaction analysis (BIA) for biology and biochemistry. This article first gives
      an overview of the historical development of different transducer principles used
      for the detection of BIA. Subsequently, the four major parts of a biosensor
      system: transducer, sample handling, surface/immobilization chemistry and test
      formats/data evaluation will be discussed, with a main focus on the test formats
      and data evaluation. The intention of this review is to present an introduction
      to the field and to point out the difficulties most frequently encountered.

PMID- 11225771
TI  - Amperometric biosensors based on electrosynthesised polymeric films.
AB  - The most significant goals achieved in the course of the last decade in the
      design of amperometric biosensors based on redox enzymes entrapped in
      electrosynthesised polymeric films are reviewed. Particular emphasis is devoted
      to non-conducting polymers with built-in permselectivity that revealed very
      promising materials for designing fast-response and interference-free, H2O2
      detecting, amperometric biosensors. The role of surface analytical techniques to
      provide structural information allowing a better understanding of polymers
      properties and their relationship with the ultimate performance of the final
      device is also outlined. The most relevant applications of amperometric
      biosensors based on electropolymerised films to real samples analysis are also
      reviewed and some possible future trends highlighted.

PMID- 11225772
TI  - Thickness shear mode resonators ("mass-sensitive devices") in bioanalysis.
AB  - A short overview of function and experimental set-ups of acoustic wave devices is
      given which, in contrast to other bioanalysis techniques, are based on a
      mechanical transduction mechanism. The most frequently used device is the
      thickness shear mode resonator (TSMR), which in the last few years was
      intensively employed in biosensor applications. TSMR biosensor studies in the
      field of nucleic acid interaction, adsorption of proteins to surfaces and
      immunosensing are reviewed. A main point concerns the interpretation of the
      sensor response not only in terms of mass loading, which underestimates the
      capabilities of these devices.

PMID- 11225773
TI  - Characterization of implantable biosensor membrane biofouling.
AB  - The material-tissue interaction that results from sensor implantation is one of
      the major obstacles in developing viable, long-term implantable biosensors.
      Strategies useful for the characterization and modification of sensor
      biocompatibility are widely scattered in the literature, and there are many
      peripheral studies from which useful information can be gleaned. The current
      paper reviews strategies suitable for addressing biofouling, one aspect of
      biosensor biocompatibility. Specifically, this paper addresses the effect of
      membrane biofouling on sensor sensitivity from the standpoint of glucose
      transport limitations. Part I discusses the in vivo and in vitro methods used to
      characterize biofouling and the effects of biofouling on sensor performance,
      while Part II presents techniques intended to improve biosensor biocompatibility.

PMID- 11225774
TI  - Electrochemical immunoassays.
AB  - Immunoassays (IA) use the specific antigen antibody complexation for analytical
      purposes. Radioimmunoassays (RIA), fluorescence immunoassays (FIA) and enzyme
      immunoassays (EIA) are well established in clinical diagnostics. For the
      development of hand-held devices which can be used for point of care
      measurements, electrochemical immunoassays are promising alternatives to existing
      immunochemical tests. Moreover, for opaque or optically dense matrices
      electrochemical methods are superior. Potentiometric, capacitive and amperometric
      transducers have been applied for direct and indirect electrochemical
      immunoassays. However, due to their fast detection, broad linear range and low
      detection limit, amperometric transducers are preferred. Competitive and
      noncompetitive amperometric immunoassays have been developed with redox compounds
      or enzymes as labels. This review will give an overview of the most frequently
      applied principles in electrochemical immunoassays. The potential of an indirect
      competitive amperometric immunoassay for the determination of creatinine within
      nanomolar range and the circumvention of the most serious problem in
      electrochemical immunoassays, namely regeneration, will be discussed.

PMID- 11225775
TI  - Immunochromatographic techniques--a critical review.
AB  - Hyphenated techniques have become very popular during the last decade.
      Nevertheless, the use of biochemical methods, such as immunoassays, in
      conjunction with instrumental methods, such as chromatography, have not gained
      widespread acceptance. This review critically discusses many of the implemented
      and potential options for such coupled systems or components, which might be
      useful for such systems, including immunoaffinity extraction, immunoaffinity
      chromatography, immunochemical detectors, immunoblotting, receptor assays, enzyme
      inhibition assays, displacement assays, flow-injection immunoassays, miniaturized
      techniques and stationary phases such as restricted access materials or
      molecularly imprinted polymers. The performance of immunochromatographic systems
      is discussed regarding their ability to solve highly complex and demanding
      analytical problems.

PMID- 11225776
TI  - Immunoanalytical techniques for pesticide monitoring based on fluorescence
      detection.
AB  - In the field of environmental analysis there is still great potential for
      development and application of immunoanalytical techniques (IT). Heterogeneous
      and homogeneous immunoassays (IA), flow-injection immunoanalysis (FIIA) and
      immunosensors (IS) with different detection principles have been developed. In
      this review we focus on fluorescence methods for pesticide monitoring published
      since 1992. These techniques offer a high degree of selectivity and, in
      principle, sensitivity. Restrictions on the limits of detection (LOD) due to
      background signals are minimized by development of solid-phase separation
      systems, new fluorescent probes, and new instrumentation.

PMID- 11225777
TI  - Immunosensors in clinical analysis.
AB  - Clinical analysis requires methods of high reliability. The importance of
      immunosensors in clinical analysis is discussed. Due to the fact that the
      construction of immunosensors plays a very important role in their response
      characteristics, different types of immunosensor designs are highlighted. The
      performances of immunosensors are discussed taking into account the type of
      transducer utilized for construction.

PMID- 11225778
TI  - Nano-electrospray ionization mass spectrometry: addressing analytical problems
      beyond routine.
AB  - The advent of nano-electrospray ionization (nano-ESI) has considerably extended
      the usability of ESI in the analytical mass spectrometric laboratory. One of the
      remarkable features of nano-ESI is its extremely low sample consumption. Only a
      few microliters of analyte solution (10(-5)-10(-8) M) are sufficient for
      molecular weight determination and structural investigations by MS/MS. But nano
      ESI is more than just a minimized-flow ESI; the low solvent flow rate also
      affects the mechanism of ion formation. As a consequence, the area of ESI-MS
      applications is significantly enhanced. Oligosaccharides, glycosides as well as
      glycoproteins can be analyzed more easily than with normal ion spray. The same
      holds for the analysis of non-covalent complexes sprayed directly from aqueous
      solutions.

PMID- 11225779
TI  - Mass spectrometric identification of proteins and characterization of their post
      translational modifications in proteome analysis.
AB  - High-throughput DNA sequencing has resulted in increasing input in protein
      sequence databases. Today more than 20 genomes have been sequenced and many more
      will be completed in the near future, including the largest of them all, the
      human genome. Presently, sequence databases contain entries for more than 425.000
      protein sequences. However, the cellular functions are determined by the set of
      proteins expressed in the cell--the proteome. Two-dimensional gel
      electrophoresis, mass spectrometry and bioinformatics have become important tools
      in correlating the proteome with the genome. The current dominant strategies for
      identification of proteins from gels based on peptide mass spectrometric
      fingerprinting and partial sequencing by mass spectrometry are described. After
      identification of the proteins the next challenge in proteome analysis is
      characterization of their post-translational modifications. The general problems
      associated with characterization of these directly from gel separated proteins
      are described and the current state of art for the determination of
      phosphorylation, glycosylation and proteolytic processing is illustrated.

PMID- 11225780
TI  - Interfacing matrix-assisted laser desorption/ionization mass spectrometry with
      column and planar separations.
AB  - This paper presents a critical review of off-line and on-line coupling of matrix
      assisted laser desorption/ionization (MALDI) mass spectrometry to liquid column
      separations (e.g. HPLC, GPC and CE) and planar separations (e.g. PAGE and TLC).
      Off-line MALDI analysis of fractions collected from HPLC, GPC and CE or spots
      scraped and extracted from TLC and PAGE has already become a routine practice for
      many laboratories. MALDI has also been used to obtain mass spectra directly from
      TLC plates and PAGE. The direct analysis methods range from dot-blotted samples
      to two-dimensional scanning of the entire gels/plates. Various combinations of on
      line coupling of MALDI with column separations are also reviewed. The review
      discusses the strengths and limitations associated with different off-line and on
      line coupling approaches.

PMID- 11225781
TI  - Mass spectrometry for direct determination of proteins in cells: applications in
      biotechnology and microbiology.
AB  - A number of different procedures have been developed in recent years that utilize
      mass spectrometry for the direct determination of proteins in complex mixtures of
      biological origin. Specific examples of these include the use of matrix-assisted
      laser desorption/ionization mass spectrometry (MALDI-MS) or directly combined
      liquid chromatography-electrospray ionization mass spectrometry (LC/ESI-MS) for
      rapid profiling of protein expression in bacterial and eucaryotic cells and cell
      free extracts. Approaches to sample cleanup, contaminant removal, and initial
      separation of analytes on-line for the direct determination of proteins in cells
      using MALDI- and ESI-MS are discussed. Advantages of these techniques over
      traditional biochemical methods are highlighted, and a critical review of their
      utility and potential as standard tools in the biomolecular and microbiological
      research laboratory is presented.

PMID- 11225782
TI  - Infrared and Raman imaging of biological and biomimetic samples.
AB  - Established methods for imaging of biological or biomimetic samples, such as
      fluorescence and optical microscopy, magnetic resonance imaging (MRI), X-ray
      tomography or positron emission tomography (PET) are currently complemented by
      infrared (both near-IR and mid-IR) as well as Raman spectroscopic imaging,
      whether it be on a microscopic or macroscopic scale. These vibrational
      spectroscopic techniques provide a wealth of information without a priori
      knowledge of either the spectral data or the composition of the sample. Infrared
      radiation does not harm the organism, no electric potential needs to be applied,
      and the measurements are not influenced by electromagnetic fields. In addition,
      no extrinsic labeling or staining, which may perturb the system under
      investigation, has to be added. The immense volume of information contained in
      spectroscopic images requires multivariate analysis methodologies in order to
      effectively mine the chemical and spatial information contained within the data
      as well as to analyze a time-series of images in order to reveal the origin of a
      chemical or biochemical process. The promise and limitations of this new
      analytical tool are surveyed in this review.

PMID- 11225783
TI  - Vibrational circular dichroism: a new spectroscopic tool for biomolecular
      structural determination.
AB  - Vibrational circular dichroism (VCD) in the past two decades has developed into a
      powerful new structural tool. A concise review of the applications of VCD to
      determine the structures of various biological molecules, namely peptides and
      proteins, nucleic acids and carbohydrates, is provided.

PMID- 11225784
TI  - Scanning electrochemical microscopy: a new way of making electrochemical
      experiments.
AB  - A short review is given on scanning electrochemical microscopy (SECM). The
      historic background of the technique is briefly summarized and the basic
      principles outlined. The three different directions of its use: chemical
      microscopic imaging, the measuring of physicochemical constants and coefficients,
      and use as a micromachining tool are briefly discussed. The general built-up of
      the SECM apparatus is described. Preparation and use of several different
      measuring tips are introduced. A few examples are given of the application of
      SECM measurement in different studies.

PMID- 11225785
TI  - Single-molecular detection in solution: a new tool for analytical chemistry.
AB  - Single-molecule detection (SMD) is becoming more and more popular in the
      scientific community and is on the threshold to become a technique for laboratory
      use. Therefore, conceivable applications as well as optimized conditions for SMD
      will be discussed. To point out the possibilities of SMD, the signal-to
      background ratio and the detection efficiency, in combination with the
      probability of misclassification, will be contemplated.

PMID- 11225786
TI  - Bio- and chemiluminescence in bioanalysis.
AB  - Analytical chemiluminescence and bioluminescence represent a versatile,
      ultrasensitive tool with a wide range of applications in diverse fields such as
      biotechnology, pharmacology, molecular biology, clinical and environmental
      chemistry. Enzyme activities and enzyme substrates and inhibitors can be
      efficiently determined when directly involved in luminescent reactions, and also
      when they take part in a reaction suitable for coupling to a final light-emitting
      reaction. Chemiluminescence detection has been exploited in the fields of flow
      injection analysis and column-liquid chromatographic and capillary
      electrophoretic separative systems, due to its high sensitivity when compared
      with colorimetric detection. It has widely been used as an indicator of reactive
      oxygen species formation in cells and whole organs, thus allowing the study of a
      number of pathophysiological conditions related to oxidative stress.
      Chemiluminescence represents a sensitive and rapid alternative to radioactivity
      as a detection principle in immunoassays for the determination of a wide range of
      molecules (hormones, food additives, environmental pollutants) and in filter
      membrane biospecific reactions (Southern, Northern, Western, dot blot) for the
      determination of nucleic acids and proteins. Chemiluminescence has also been used
      for the sensitive and specific localization and quantitation of target analytes
      in tissue sections and single cells by immunohistochemistry and in situ
      hybridization techniques. A relatively recent application regards the use of
      luminescent reporter genes for the development of bioassays based on genetically
      engineered microorganisms or mammalian cells able to emit visible light in
      response to specific inorganic and organic compounds. Finally, the high
      detectability and rapidity of bio- and chemiluminescent detection make it
      suitable for the development of microarray-based high throughput screening
      assays, in which simultaneous, multianalyte detection is performed on multiple
      samples.

PMID- 11225787
TI  - Photoproteins as luminescent labels in binding assays.
AB  - Certain marine organisms produce calcium-activated photoproteins that allow them
      to emit light for a variety of purposes, such as defense, feeding, breeding, etc.
      Even though there are many bioluminescent organisms in nature, only a few
      photoproteins have been isolated and characterized. The mechanism of emission of
      light in the blue region is the result of an internal chemical reaction. Because
      there is no need for excitation through external irradiation for the emission of
      bioluminescence, the signal produced has virtually no background. This allows for
      the detection of the proteins at extremely low levels, making these photoproteins
      attractive labels for analytical applications. In that regard, the use of certain
      photoproteins, namely, aequorin, obelin, and the green fluorescent protein as
      labels in the design and development of binding assays for biomolecules has been
      reviewed. In addition, a related fluorescent photoprotein, the green fluorescent
      protein (GFP), has been recently employed in bioanalysis. The use of GFP in
      binding assays is also discussed in this review.

PMID- 11225788
TI  - Reporter gene bioassays in environmental analysis.
AB  - In parallel to the continuous development of increasingly more sophisticated
      physical and chemical analytical technologies for the detection of environmental
      pollutants, there is a progressively more urgent need also for bioassays which
      report not only on the presence of a chemical but also on its bioavailability and
      its biological effects. As a partial fulfillment of that need, there has been a
      rapid development of biosensors based on genetically engineered bacteria. Such
      microorganisms typically combine a promoter-operator, which acts as the sensing
      element, with reporter gene(s) coding for easily detectable proteins. These
      sensors have the ability to detect global parameters such as stress conditions,
      toxicity or DNA-damaging agents as well as specific organic and inorganic
      compounds. The systems described in this review, designed to detect different
      groups of target chemicals, vary greatly in their detection limits, specificity,
      response times and more. These variations reflect on their potential
      applicability which, for most of the constructs described, is presently rather
      limited. Nevertheless, present trends promise that additional improvements will
      make microbial biosensors an important tool for future environmental analysis.

PMID- 11225789
TI  - How to ablate typical atrial flutter.

PMID- 11225790
TI  - The syndrome of right bundle branch block ST segment elevation in V1 to V3 and
      sudden death--the Brugada syndrome.
AB  - In 1992 a new syndrome was described consisting of syncopal episodes and/or
      sudden death in patients with a structurally normal heart and an
      electrocardiogram (ECG) characteristic of right bundle branch block with ST
      segment elevation in leads V1 to V3. The disease is genetically determined, with
      an autosomal dominant pattern of transmission. Three different mutations that
      affect the structure and function of the cardiac sodium channel gene SCN5A have
      been identified. Two mutations result in total loss of function of the sodium
      channel. The other mutation results in acceleration of the recovery of the sodium
      channel from inactivation. The incidence of the disease is difficult to estimate,
      but it causes 4 to 10 sudden deaths per 10000 inhabitants per year in areas like
      Thailand and Laos. In these countries, the disease represents the most frequent
      cause of death in young adults. Up to 50% of the yearly sudden deaths in patients
      with a structurally normal heart are caused by this syndrome. The diagnosis is
      easily made by means of the ECG. The presence of concealed and intermittent
      forms, however, make the diagnosis difficult in some patients. The ECG can be
      modulated by changes in autonomic balance and the administration of
      antiarrhythmic drugs. Beta-adrenergic stimulation normalizes the ECG, while
      intravenous ajmaline, flecainide or procainamide accentuate ST segment elevation
      and are capable of unmasking concealed and intermittent forms of the disease.
      Recent data suggest that loss of the action potential dome in the right
      ventricular epicardium but not the endocardium underlies ST segment elevation
      seen in the Brugada syndrome. Also, electrical heterogeneity within the right
      ventricular epicardium leads to the development of closely coupled extrasystoles
      via a phase 2 reentrant mechanism, which then precipitates ventricular
      tachycardia-ventricular fibrillation. Right ventricular epicardium is
      preferentially affected because of the predominance of transient outward current
      in this tissue. Antiarrhythmic drugs like amiodarone and beta-blockers do not
      prevent sudden death in symptomatic or asymptomatic individuals. Gene therapy may
      offer a cure in future years. Implantation of an automatic cardioverter
      defibrillator is the only currently proven effective therapy.

PMID- 11225791
TI  - Pacemaker upgrades from ventricular to dual chamber.

PMID- 11225792
TI  - Upgrade to dual chamber pacing after long-term ventricular stimulation:
      feasibility and intermediate term follow-up.
AB  - AIMS: To evaluate the feasibility and follow-up results of atrial lead
      implantation and a change to dual chamber pacing following long-term treatment
      with single chamber ventricular stimulation. METHODS AND RESULTS: During a 30
      month period, 70 consecutive patients with ventricular pacemakers were referred
      for pulse generator exchange or lead reoperation. Using defined criteria, an
      upgrade procedure was considered indicated in 34 of the cases (49%); these
      patients had a mean age of 74.8+/-8.8 years, and had been treated with VVI or
      VVIR pacing for a mean time of 7.8+/-3.8 years (range 1.8-17). An atrial lead was
      successfully implanted via ipsilateral subclavian venipuncture through the
      existing pectoral pacemaker pocket in 33 of the 34 cases (97% of the attempts).
      Postoperatively, one atrial lead dislodgement was seen, and another patient
      required atrial lead adjustment due to P wave undersensing. The mean follow-up
      period was 14+/-10 months. During this time, four patients developed permanent
      atrial fibrillation (annual incidence 11%. In 82% of the patients in whom an
      upgrade procedure was attempted, dual chamber pacing was maintained at the end of
      follow-up. CONCLUSION: Restoration of AV synchrony is possible in a substantial
      proportion of patients treated with long-term ventricular stimulation. Atrial
      lead placement through ipsilateral subclavian venipuncture is generally feasible,
      and the vast majority of cases remain in dual chamber pacing with normal function
      during intermediate term follow-up.

PMID- 11225793
TI  - Dual chamber pacing with optimal AV delay in congestive heart failure: a
      randomized study.
AB  - AIM: A prospective randomized trial was set up to evaluate contractile parameters
      and quality of life in patients with congestive heart failure. METHODS AND
      RESULTS: We describe the results from 38 patients in sinus rhythm and with
      chronic heart failure due to congestive cardiomyopathy, prospectively randomized
      to optimal medical therapy (Group 1, 19 patients) or optimal medical therapy plus
      dual chamber pacemaker programmed to optimal AV delay (Group 2, 19 patients). At
      a 6 month follow-up, 7/19 patients in Group 1 had died compared with 5/19
      patients in Group 2. During follow-up, there were few significant changes in
      evaluated parameters except for mitral regurgitation time, which was prolonged in
      Group 1 and shortened in Group 2. The systolic left ventricular diameter
      shortened significantly only in Group 2. An energy and activity questionnaire
      showed that the effect of DDD pacing in the latter patient population was
      beneficial. CONCLUSIONS: From these results we may conclude that at the 6 month
      follow-up DDD pacing with echo-optimized AV interval programming can improve
      quality of life without affecting survival.

PMID- 11225794
TI  - Internal low-energy cardioversion: a therapeutic option for restoring sinus
      rhythm in chronic atrial fibrillation after failure of external cardioversion.
AB  - AIMS: Conventional external cardioversion remains the technique of choice for
      restoration of sinus rhythm in patients with chronic atrial fibrillation (AF).
      Recent reports have suggested that internal low-energy cardioversion is efficient
      and safe in terminating AF in patients with failed external cardioversion.
      METHODS AND RESULTS: In 20 of 118 consecutive patients with spontaneous chronic
      AF (>7/days), who underwent low-energy cardioversion, one or more attempts at
      restoring sinus rhythm with external cardioversion had failed. Low-energy
      internal cardioversion was performed under light sedation. Shocks were delivered
      (using an external custom defibrillator) between two nonapolar catheters
      positioned in the right atrium (cathode) and in the coronary sinus (anode). Heart
      disease was present in 12 and absent in eight patients ('lone' atrial
      fibrillation). Atrial fibrillation was established for a period ranging from 12
      days to 53 months. Low-energy internal cardioversion restored sinus rhythm in 15
      of the 20 patients (75%) with a mean energy of 4.5+/-1.2 J, a mean conversion
      voltage of 355+/-53 V and a mean impedance of 63+/-8 ohms. No complications were
      observed. With a mean follow-up of 6+/-7 months, 11 patients (73%) were in stable
      sinus rhythm. CONCLUSIONS: This study provides evidence in support of low-energy
      internal cardioversion as a valuable therapeutic option in patients in whom
      conventional external cardioversion failed. This technique is safe and does not
      require general anaesthesia.

PMID- 11225796
TI  - Electrophysiological properties of the recipient atrial remnant after human
      orthotopic cardiac transplantation.
AB  - AIMS: The recipient atrial remnant has been used as a control in studies
      ofchronotropic response following orthotopic cardiac transplantation and as a
      trigger for the donor heart. It is not known, however, whether its function is
      normal. We investigated the electrophysiological properties of the recipient
      atrial remnant. METHODS AND RESULTS: Fifty patients were studied, mean age 49
      years (range 20-63) and mean time post-orthotopic cardiac transplantation of 31
      months (range 1-107). Recipient atrial rhythm, spontaneous cycle length and sinus
      node function were determined. Atrial fibrillation/flutter was identified in
      10/50 (20%). Of those in sinus rhythm, significant bradycardia was present in
      12/40 (30%). The mean spontaneous cycle length was 929+/-188 ms. Three patients
      demonstrated variable atrial electrocardiogram morphology and a further three
      patients had marked variations in resting cycle length. The sinus node function
      was abnormal in 2/34 (6%). CONCLUSIONS: Only 56% recipient atria had normal sinus
      rhythm, with 21% of these demonstrating features consistent with a wandering
      atrial pacemaker. The recipient atrial remnant is not normal in the majority of
      transplant recipients and should be used with caution in studies involving its
      use as a control or as a trigger for the donor heart.

PMID- 11225795
TI  - Head-up tilt testing potentiated with oral nitroglycerin: a randomized trial of
      the contribution of a drug-free phase and a nitroglycerin phase in the diagnosis
      of neurally mediated syncope.
AB  - BACKGROUND: Since the pharmacological challenge with nitroglycerin (NTG) follows
      the initial drug-free phase in current tilt testing protocols, the effects of
      nitroglycerin alone and the appropriate duration of the basal phase are unknown.
      METHODS: To optimize the test, a randomized intra-patient comparison of two
      protocols was undertaken: a conventional nitroglycerin test (cHUT) consisting of
      passive upright posture at 60 degrees for 45 min followed, if negative, by
      sublingual NTG 0.4 mg spray, with the test continued for 20 min; and, accelerated
      nitroglycerin test (aHUT) consisting of passive upright posture at 60 degrees for
      5 min--to rule out orthostatic hypotension--followed by sublingual NTG 0.4 mg
      spray, with the test continued for 20 min. Eighty-four consecutive patients (33
      males; mean age 55+/-22) with unexplained syncope underwent both cHUT and aHUT in
      a randomized sequence with a 24-72 h interval between them. Additionally, 25 age
      matched control subjects underwent aHUT. RESULTS: In the drug-free phase, cHUT
      was positive in 15/84 patients (18%) and aHUT in 1/84 patients (1%). After NTG,
      cHUT and aHUT showed the same positivity rate of 33% (28/84 patients). The
      overall positivity rate was therefore higher with cHUT than with aHUT (51% vs
      35%, P=0.04). Times to syncope were 29+/-12 min, (range 2-44) for cHUT drug-free
      phase, 5+/-2 min (range 2-9) for cHUT NTG phase, and 5+/-2 min (range 2-9) for
      aHUT. Only one (4%) of the control subjects had a positive response to aHUT.
      CONCLUSIONS: The contribution of NTG to the diagnosis is independent of the
      presence of an unmedicated phase. The appropriate duration of the NTG phase is 10
      min. aHUT has good specificity, but a positivity rate lower than cHUT; thus a
      drug-free phase is necessary to increase the sensitivity of the test.

PMID- 11225798
TI  - The use of a "side-wire" permanent transvenous pacing electrode for left
      ventricular pacing.
AB  - It has been reported that biventricular pacing can improve the symptomatic status
      of patients with heart failure. However, using currently available transvenous
      left ventricular pacemaker leads the implantation procedure is difficult and has
      a high failure rate. We report the successful use of a new type of left
      ventricular pacing lead, the 'side-wire' pacing lead. This lead is initially
      introduced through a specifically designed guiding sheath to aid coronary sinus
      cannulation and then over a pre-positioned guide wire to aid final positioning.
      The more widespread introduction of this type of left ventricular pacing lead may
      reduce the difficulty of left ventricular pacing via the coronary sinus and thus
      improve the overall success rate of this therapeutic approach.

PMID- 11225799
TI  - Pacing lead entanglement in the tricuspid valve apparatus during implantation.

PMID- 11225797
TI  - Relationship between atrioventricular delay, QT interval and cardiac function in
      patients with implanted DDD pacemakers.
AB  - QT interval may change when cardiac function is improved by optimizing the
      atrioventricular the (AV) delay. The relationship between AV delay, QT interval
      and cardiac function in patients with implanted DDD pacemakers was studied in 12
      patients (aged 71+/-12 SD years) with complete or high degree AV block. Cardiac
      output (CO) was measured using a Swan-Ganz catheter or by continuous Doppler
      echocardiography. The pacing rate was fixed at 70-80/min to eliminate the
      influence of heart rate. The AV delay was prolonged stepwise by 30 ms starting
      from 90 ms. All measurements were performed after 5 min of pacing. When the AV
      delay was prolonged, the CO and QT interval gradually increased and reached a
      peak, and then decreased. When the CO was increased from the minimum to the
      maximum value by optimizing the AV delay, the QT interval was significantly
      prolonged from 440+/-40 to 456+/-39 ms (P<0.002). The CO increased from 5.5+/-2.5
      to 6.0+/-2.5 l x min(-1) (P<0.002) when the AV delay was changed, during which
      the QT interval was prolonged from the minimum to the maximum value. There was a
      significant positive correlation between the optimal AV delay at which CO was
      maximal (161+/-33 ms) and the optimal AV delay predicted from the maximum QT
      interval (167+/-29 ms, r=0.85, P<0.001). In conclusion, the optimal AV delay can
      be predicted from the QT interval.

PMID- 11225800
TI  - Recurrent cardioembolic stroke related to late dislodgement of a right atrial
      pacing lead into the left atrium.
AB  - A 76-year-old woman had a permanent transvenous DDDR pacemaker implanted for
      complete atrioventricular block. She was hospitalized 4 years later for recurrent
      transient ischaemic attacks related to dislodgment of the atrial lead into the
      left atrium through a patent foramen ovale. The patient was successfuly treated
      by transvenous extraction of the atrial lead. The follow-up has been uneventful
      12 months after the procedure. Left atrially dislodged pacemaker leads have to be
      retracted under full anticoagulation.

PMID- 11225801
TI  - Biventricular implantable cardioverter defibrillator use in a patient with heart
      failure and ventricular tachycardia secondary to Emery-Dreifuss syndrome.
AB  - We report a case of fully transvenous single-unit biventricular implantable
      cardioverter defibrillator (ICD) use in a 43-year-old woman with a manifesting
      carrier form of muscular dystrophy (Emery-Dreifuss syndrome). The indication for
      biventricular ICD use was progressive heart failure with ventricular arrhythmia,
      permanent atrial fibrillation and previous VVIR pacemaker insertion. Single-unit
      transvenous biventricular ICD implantation was undertaken without complication.
      No potentially serious device malfunction was noted during subsequent follow-up.
      We conclude that single-unit biventricular ICD implantation is feasible for
      pacing and ventricular tachyarrhythmia control in patients with underlying atrial
      fibrillation.

PMID- 11225802
TI  - Chemical measurement and the law.

PMID- 11225803
TI  - An immune algorithm for resolution of multicomponent overlapping chromatograms.
AB  - A novel immune algorithm for resolution and quantitative determination of the
      components in overlapping chromatograms was proposed by imitating biological
      immune systems. The algorithm takes an overlapping chromatogram as its input and
      subtracts the chromatograms of standard samples from the input by iteration of a
      network. When the residual does not change, the network will converge and
      chromatographic information of the components in overlapping chromatogram will be
      obtained. Both simulated and experimental data sets were investigated by the
      method. Results showed that both resolved results and recoveries of quantitative
      determination are satisfactory. Comparing with conventional least-square method,
      the immune algorithm is fast in calculation.

PMID- 11225804
TI  - Quantification of sterols, 5alpha- and 5beta-stanols in sewage sludge, manure and
      soils amended with these both potential fertilizers.
AB  - A method for the quantitative determination of sterols, 5alpha- and 5beta-stanols
      is proposed to characterize the lipid fraction of two potential organic
      fertilizers, like sewage sludge and manure, as well as soils amended by them. It
      was possible to determine the kind of fertilizer added to the soil. Further
      studies were conducted to determine the accumulative effects of steroids in soils
      treated with manure and different doses of sewage sludge.

PMID- 11225805
TI  - Application of solid phase micro extraction for the rapid analysis of chlorinated
      organics in breast milk.
AB  - The method presented here allows the monitoring of persistent organochlorine
      compounds in breast milk using the solid phase microextraction technique (SPME)
      and gas chromatography with electron capture detection (GC-ECD). It describes the
      determination of hexachlorobenzene (HCB), alpha-, beta-, and gamma
      hexachlorocyclohexane (HCH), dichlorodiphenyltrichloroethane (DDT) and its
      derivatives, and some important congeners of the polychlorinated biphenyls (PCB).
      Also included are more polar substances such as tri-, tetra- and penta
      chlorophenols, which can be analyzed simultaneously with the afore-mentioned less
      polar compounds without the need of a derivatization for the determination of the
      phenolic compounds. The reproducibility of the results is very good down to the
      lower microg/L-region. The method is very fast and of low cost compared to the
      classic extraction and determination procedures.

PMID- 11225806
TI  - Spectrophotometric flow injection determination of total phosphorus in beer using
      on-line UV/thermal induced digestion.
AB  - A flow injection system for the automatic determination of total phosphorus in
      beer is described. The developed manifold uses a two-stage photooxidation/thermal
      digestion procedure together with oxidizing and hydrolyzing reagents to convert
      all forms of phosphorus compounds to orthophosphate. Polyphosphates are
      hydrolyzed by acid and heat, and organo-phosphates are digested by UV-catalyzed
      peroxodisulfate oxidation. The orthophosphate formed is then
      spectrophotometrically determined by the phosphomolybdenum blue reaction, using
      stannous chloride as reducing agent. The results obtained for a set of 19 beer
      samples (with concentrations from 120 to 735 mg P/L) were in good agreement with
      the reference method, the maximum relative deviation found being 4.7%. Relative
      standard deviations for ten consecutive determinations were lower than 1.5%, and
      a detection limit of 1 mg P/L was achieved.

PMID- 11225810
TI  - Investigation of microwave assisted drying of samples and evaporation of aqueous
      solutions in trace element analysis.
AB  - Investigations of microwave assisted drying of sample materials and microwave
      assisted evaporation of aqueous sample solutions and acidic digestion residues
      were accomplished by means of special rotors for the microwave digestion system
      MULTIWAVE. To check the results obtained by microwave assisted drying, the
      samples were also conventionally dried at 105 degrees C in an oven. The following
      samples have been dried: 10 g each of meat, fish, apple, cucumber, potato,
      mustard, yogurt, clay and marl; 1 g each of certified reference material TORT 2
      (lobster hepatopancreas), BCR 278 (mussel tissue) and BCR 422 (cod muscle); 500 g
      garden mould. Microwave assisted drying takes 40 min for organic samples and 30
      min for inorganic material. Important is a slow increase of microwave power
      during the first 20 min. The results agree well with conventional drying at 105
      degrees C. Losses of As, Se and Hg have been investigated for 3 CRMs. Only Se
      shows losses in the range of 20%. Losses of As, Be, Cd, Co, Cr, Cu, Fe, Hg, Li,
      Mg, Mn, Mo, Ni, Pb, Sb, Se, Sr, Ti, Tl, V and Zn after evaporation of aqueous
      samples and acidic solutions after wet digestion, respectively, have been
      investigated. 50 mL aqueous solution was evaporated almost to dryness within 25
      min. The recovery of Hg is 40-50%, of Se 90-95% and of the other elements 97
      102%. 0.2 g each of TORT 2, BCR 278 and BCR 422 have been digested with 4 mL
      nitric acid and 1 mL hydrochloric acid by means of the microwave digestion system
      MULTIWAVE. The digestion residue was evaporated almost to dryness and dissolved
      again in 10 mL diluted nitric acid. In this case no element losses have been
      observed. The measured concentration of As, Cd, Cu, Fe, Mn, Hg, Pb, Mo, Ni, Se,
      Sr, V and Zn agree very well with the certified values. An important prerequisite
      for good recoveries is not to evaporate the solutions to complete dryness.

PMID- 11225811
TI  - In-situ monitoring of protein labeling reactions by matrix-assisted laser
      desorption/ionization mass spectrometry.
AB  - Taking the labeling reaction of horse heart cytochrome c or ubiquitin with
      biotinamidocaproate N-hydroxysucchinimide ester (biotin-NHS) as test cases, this
      report demonstrates the usefulness of matrix-assisted laser desorption/ionization
      (MALDI) mass spectrometry for in-situ monitoring of the labeling process and for
      determining the composition of the labeled products without the need for prior
      separation. The effects of pH and starting materials concentration on the
      labeling process were investigated in detail. Our MALDI MS results show that: (1)
      labeled products are always mixtures of different conjugates, which may explain
      peak broadening found in chromatographic studies of labeling reactions; (2) the
      higher conjugate fractions become more prominent as the labeling reaction
      proceeds, with a concomitant exponential decline of the lower conjugate
      fractions; (3) biotin-NHS can be incorporated into peptides and protein in a
      stepwise and controlled manner simply by adjusting the molar ratio of the
      starting materials.

PMID- 11225815
TI  - Mercury determination with ICP-MS: signal suppression by acids.
AB  - When mercury is quantified by ICP-MS under routine conditions (external
      calibration) in reference materials, which require mineralization with nitric
      acid, the experimental concentrations are almost always unacceptably low in
      comparison to certified values. Sorption of mercury on the Teflon surfaces of the
      digestion vessels, changes in the viscosity of the aspirated solutions, in the
      efficiency of the nebulization, in the aerosol transport, and memory effects
      cannot be responsible for the low results. The intensity of a mercury signal is
      strongly dependent on the concentration of nitric acid (and other mineral acids)
      in the measured solutions. Correct results for mercury in the SRM GBW-90101
      (Chinese human hair; 2.16+/-0.21 mg Hg/kg certified) can only be obtained, when
      the solutions, with which the external calibration curves were established, have
      exactly the same nitric acid concentration as the aspirated digests (2.03+/-0.01
      mg Hg/kg; n = 5), when mercury is determined by the standard addition method
      (2.10+/-0.01 mg Hg/kg; n = 5), or when the experimental mercury concentration
      obtained at a nitric acid concentration in the digest, different from the
      concentration in the external calibration solutions, is corrected mathematically
      based on a pre-established function [Hg2+] = f [HNO3]. The concentrations found
      by this mathematically based correction 2.04+/-0.01 mg Hg/kg (n = 5) is in good
      agreement with the values obtained by acid matched calibration or by the standard
      addition method. For practical work with large numbers of samples the
      mathematical correction appears to be the method of choice. For occasional
      mercury determinations, the standard addition method seems to be the most
      practicable.

PMID- 11225818
TI  - Routine analysis of ultra pure water by ICP-MS in the low- and sub-ng/L level.
AB  - The chemical analysis with inductively coupled plasma-mass spectrometry (ICP-MS)
      can help to examine the purity of ultra pure water (UPW) down to 10 part per
      trillion (ng/L) and lower. For a proper determination of a high number of samples
      per week the analysis must be divided into two parts: the routine analysis and
      the reference water analysis. The routine analysis is done by direct measurement
      of the ultra pure water samples. Applying a standard addition method under
      particular clean conditions, the reference water analysis leads to the definition
      of the accurate zero. A quick evaluation scheme is also presented for the
      reference water analysis. The method is tested for its fitness for application by
      examining LOD (for relevant element < 2 ng/L), reproducibility and linearity of
      calibration. The ICP-MS was optimized according to the methodology of G. Taguchi
      to improve reproducibility and LOD.

PMID- 11225821
TI  - Application of ion-chromatography for the determination of the organic-group
      parameters AOCl, AOBr and AOI in water.
AB  - A method of differential AOX-analysis, i.e. the simultaneous determination of
      AOCl, AOBr and AOI is described. Individual steps of the method including
      enrichment at activated carbon, combustion in an oxygen stream and ion
      chromatographic detection were optimized. In most cases quantitative recoveries
      of various organic Cl, Br and I containing substances of different polarity and
      structure were obtained. The method was applied to the determination of AOX
      fractions in municipal and hospital wastewater. A good agreement between
      conventional coulometric and the described ion-chromatographic determination was
      found. High concentrations up to 130 microg/L I of organic iodine compounds were
      measured in the influent and effluent of a municipal treatment plant in Berlin
      and up to 10 mg/L I in a hospital waste-water.

PMID- 11225823
TI  - Determination of low-molecular-weight carboxylic acids in the ambient air and
      vehicle emissions: a review.
AB  - This review surveys analysis of airborne and vehicle emitted low-molecular-weight
      carboxylic acids. Attention is paid to providing a comprehensive coverage of
      collection techniques, sample handling, storage, extraction methods followed by a
      discussion of recent developments in carboxylic acid analysis using
      chromatographic (gas and ion chromatography) and electrophoretic (capillary
      electrophoresis) techniques. The occurrence and sources of carboxylic acids in
      the ambient air are also summarized.

PMID- 11225824
TI  - Progress in pulsed-current Karl Fischer coulometry using diaphragm-free cells.
AB  - Factors influencing the accuracy of water determinations using diaphragm-free,
      pulsed current Karl Fischer (KF) coulometry were investigated with the new
      Metrohm 756 instrument. Results obtained with commercially available reagents
      from Riedel-deHaen and Merck were compared with home-made ones that were
      especially designed to minimize the formation of iodine-consuming reduction
      products generated in the cathode reaction. Positive errors in the range 2-5%
      were found for the commercial reagents as compared to 0.2-1% for the home-made
      ones which were buffered at about pH 10 containing modifiers like chloroform,
      hexanol or ethylene glycol. Except for the composition of the KF-reagent, the
      cathode current density and the titration rate were found to be critical
      parameters for the accuracy of the determinations. For all reagents investigated,
      the best results were obtained for the maximum generator current 400 mA
      (corresponding to a current density of 1,400 mA cm(-2)) in combination with a
      maximum titration rate of 2,000 microg min(-1). Surprisingly, the errors found
      under optimum conditions for the pulse technique were always somewhat larger than
      the corresponding values obtained with continuous coulometry.

PMID- 11225825
TI  - A novel method to calculate the approximate derivative photoacoustic spectrum
      using continuous wavelet transform.
AB  - A novel method based on continuous wavelet transform (CWT) using Haar wavelet
      function for approximate derivative calculation of analytical signals is proposed
      and successfully used in processing the photoacoustic signal. An approximate nth
      derivative of an analytical signal can be obtained by applying n times of the
      wavelet transform to the signal. The results obtained from four other different
      methods--the conventional numerical differentiation, the Fourier transform
      method, the Savitzky-Golay method, and the discrete wavelet transform (DWT)
      method--were compared with the proposed CWT method; it was demonstrated that all
      the results are almost the same for signals without noise, but the proposed CWT
      method is superior to the former four methods for noisy signals. The approximate
      first and second derivative of the photoacoustic spectrum of Pr(Gly)3Cl3.3H2O and
      PrCl3.6H2O were obtained using the proposed CWT method; the results are
      satisfactory.

PMID- 11225826
TI  - Neutral bidentate organophosphorus compounds as novel ionophores for
      potentiometric membrane sensors for barium(II).
AB  - Bis(diarylphosphine oxide) naphthalene compounds are used as novel ionophores in
      plasticized poly(vinyl chloride) matrix membrane sensors for barium ions. The
      most favorable sensor was 1,2-bis(diethylphenylphosphine oxide)naphthalene
      containing potassium tetrakis(4-chlorophenyl)borate as lipophilic salt and o
      nitrophenyloctyl ether as plasticizer for ion-selective electrode membrane
      construction. The electrode showed excellent properties. It gave a linear
      response with a Nernstian slope of 30 mV per decade within the concentration
      range 10(-1)-10(-5) mol L(-1) BaCl2. The electrode exhibits a high selectivity
      towards Ba2+ with respect to Li+, Na+, K+, Rb+, Cs+, NH4+, Ag+, Mg2+, Ca2+, Sr2+,
      Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, Pb2+, Al3+, La3+, and Ce3+ ions. The
      electrode response was stable over a wide pH range (3-11). The lifetime of the
      electrode was about 2 months. It was successfully applied to the determination of
      Ba2+ contents in some rocks.

PMID- 11225827
TI  - Selective electrodes for silver based on polymeric membranes containing cali.
AB  - Silver ion-selective electrodes were prepared with polymeric membranes based on
      two calix[4]arene derivatives functionalized by two hydroxy and two
      benzothiazolylthioethoxy groups. The electrodes all gave a good Nernstian
      response of 58mV decade(-1) for silver in the activity range 5 x 10(-6)-10(-1) M,
      the limits of detection reached 10(-5.8) M and exhibited high selectivity towards
      alkali, alkaline earth and some transition metal ions. The electrode was used as
      indicator electrode in titrations of Ag+ with Cl- ion.

PMID- 11225828
TI  - An amperometric biosensor based on the coimmobilization of horseradish peroxidase
      and methylene blue on a beta-type zeolite modified electrode.
AB  - A new biosensor for the amperometric detection of hydrogen peroxide was developed
      based on the coimmobilization of horseradish peroxidase (HRP) and methylene blue
      on a beta-type zeolite modified glassy carbon electrode without the commonly used
      bovine serum albumin-glutaraldehyde. The intermolecular interaction between
      enzyme and zeolite matrix was investigated using FT-IR. The cyclic voltammetry
      and amperometric measurement demonstrated that methylene blue co-immobilized with
      HRP in this way displayed good stability and could efficiently transfer electrons
      between immobilized HRP and the electrode. The sensor responded rapidly to H2O2
      in the linear range from 2.5 x 10(-6) to 4.0 x 10(-3) M with a detection limit of
      0.3 microM. The sensor was stable in continuous operation.

PMID- 11225829
TI  - Determination of carbaryl and biphenyl through optical fiber ccd-assisted flash
      lamp induced room temperature phosphorescence.
AB  - A fiber-optic sensor for solid surface room temperature phosphorescence of
      carbaryl and biphenyl pesticides was designed. A xenon flash lamp was used as
      excitation source, and a cooled two-dimensional charge coupled device was
      employed as the detector. Room temperature phosphorescence spectra of carbaryl
      and biphenyl were recorded by an imaging spectrograph. Limits of detection at the
      picogram/spot level were obtained for the investigated compounds. The linear
      dynamic range extended over three orders of magnitude. The standard addition
      method and the internal standard method were employed to analyze the studied
      compounds in mixtures. The feasibility of the SS-RTP apparatus developed was
      evaluated by the identification of carbaryl in a real sample.

PMID- 11225830
TI  - Bulk acoustic wave sensor for herbicide assay based on molecularly imprinted
      polymer.
AB  - A novel molecularly imprinted polymer (MIP) coated bulk acoustic wave (BAW)
      sensor was fabricated for liquid phases. It can be used as a sensitive portable
      implement for the assay of 2,4-dichlorophenoxyacetic acid. A logarithmic response
      relationship between 2.0 x 10(-7) M and 5.0 x 10(-4)M was found. The detection
      limit was 1.0 x 10(-7) M. Recoveries were 93.2-108.7%. Influencing factors were
      investigated in detail and optimized.

PMID- 11225831
TI  - Fourier transform infrared determination of CO2 evolved from carbonate in
      carbonated apatites.
AB  - A quantitative method based on FTIR has been developed to determine carbonate in
      synthetic apatites. The method measures the evolved CO2 after reaction of 50 mg
      apatite with 2 mL of hydrochloric acid (0.5 M) in a reaction vessel, heated to 40
      degrees C. The CO2 evolved was swept by a carrier of nitrogen to a laboratory
      made infrared gas cell of 39 mm pathlength and 490 microL volume. The signals
      were recorded as a function of time and the areas of the chemigram peaks obtained
      from the measurements in the wavenumber range of 2,500-2,150 cm(-1), were
      interpolated using a calibration curve. The method can be used to study apatites
      with carbonate contents below 0.2% with a sampling frequency of 8 h(-1).

PMID- 11225832
TI  - Amberlite XAD-7 impregnated with Xylenol Orange: a chelating collector for
      preconcentration of Cd(II), Co(II), Cu(II), Ni(II), Zn(II) and Fe(III) ions prior
      to their determination by flame AAS.
AB  - A new chelating resin, Xylenol Orange coated Amberlite XAD-7, was prepared and
      used for preconcentration of Cd(II), Co(II), Cu(II), Fe(III), Ni(II) and Zn(II)
      prior to their determination by flame atomic absorption spectrophotometry. The
      optimum pH values for quantitative sorption of Cd(II), Co(II), Cu(II), Fe(III),
      Ni(II) and Zn(II) are 4.5-5.0, 4.5, 4.0-5.0, 4.0, 5.0 and 5.0-7.0, respectively,
      and their desorptions by 2 mol L(-1) HCl are instantaneous. The sorption capacity
      of the resin has been found to be 2.0, 2.6, 1.6, 1.6, 2.6 and 1.8 mg g(-1) of
      resin for Cd, Co, Cu, Fe, Ni and Zn, respectively. The tolerance limits of
      electrolytes, NaCl, NaF, NaI, NaNO3, Na2SO4 and of cations, Mg2+ and Ca2+ in the
      sorption of the six metal ions are reported. The preconcentration factor was
      between 50 and 200. The t1/2 values for sorption are found to be 5.3, 2.9, 3.2,
      3.3, 2.5 and 2.6 min for the six metals, respectively. The recoveries are between
      96.0 and 100.0% for the different metals at preconcentration limits between 10 to
      40 ng mL(-1). The preconcentration method has been applied to determine the six
      metal ions in river water samples after destroying the organic matter (if present
      in very large amount) with concentrated nitric acid (RSD < or = 8%, except for Cd
      for which it is upto 12.6%) and cobalt content of vitamin tablets with RSD of
      approximately 3.0%.

PMID- 11225833
TI  - Gas-chromatographic determination of chlorostyrene and dichlorostyrene isomers in
      workplace air.
AB  - Conditions for a gas-chromatographic determination of vapors and aerosols of p
      chlorostyrene and 2,6-dichlorostyrene contained in workplace air samples were
      determined. The method is based on the adsorption of p-chlorostyrene and 2,6
      dichlorostyrene on activated charcoal and fiberglass, desorption with toluene and
      analysis of the obtained solution by capillary gas chromatography with flame
      ionization detection (FID). The determination limit of the method is 5 mg m(-3)
      for each substance.

PMID- 11225834
TI  - Supercritical fluid extraction of polycyclic aromatic hydrocarbons from liver
      samples and determination by HPLC-FL.
AB  - An extraction/clean-up procedure by SFE was developed for isolating PAHs from
      liver samples for subsequent HPLC-FL determination of ten PAHs in the enriched
      extract. Recoveries (90-115%) and RSD % (< or =7.7) were satisfactory. When
      applied to 11 samples of bird of prey (Tyto alba) protected species and
      classified of special interest, from the Galicia (Northwest to Spain),
      benzo[ghi]perylene and indeno[1,2,3-cd]pyrene were undetectable; chrysene and
      benzo[a]pyrene are only detected in one sample; benzo[a]anthracene and
      benzo[k]fluoranthene are only quantified in one sample and benzo[b]fluoranthene
      in two samples. The other PAHs, anthracene, fluoranthene and pyrene are present
      in almost all the samples.

PMID- 11225836
TI  - Classification of ancient Roman glazed ceramics using the neural network of Self
      Organizing Maps.
AB  - Artificial neural networks with unsupervised learning strategy known as Self
      Organizing Maps were applied to classify ancient Roman glazed ceramics. Their
      clay ceramic bodies were analyzed by Inductively Coupled Plasma-Atomic Emission
      Spectroscopy and the chemical composition obtained was processed by this neural
      algorithm. The results obtained provide two types of information: firstly,
      classification of ceramic samples with identification of several groups and
      secondly, differentiation between the elemental chemical information. It was
      found that there are certain chemical elements which can be considered as
      principal and which can serve to differentiate between ceramics, whereas other
      elements give redundant information and do not contribute to sample
      differentiation. Seven chemical elements were considered principal and provide
      the necessary information. Two types of element were identified: 1- a group
      formed by common elements, such as: Ca, Fe, Mg, Mn and 2- another formed by
      optional elements: K or Na and Ba or Sr and Al or Ti.

PMID- 11225835
TI  - Spatial determination of elements in green leaves of oak trees (Quercus robur) by
      laser ablation-ICP-MS.
AB  - Laser ablation inductively coupled plasma mass spectrometry (laser ablation-ICP
      MS) has been applied to the spatially resolved determination of the elements Mg,
      Ca, Cu, Ni, Ba, Al, Pb, Sr and Mn in green leaves of oak trees. Instrument
      operating parameters such as the laser wavelength and the pulse energy have been
      optimized to provide the sensitivity and reproducibility required for the
      analysis. The method provides spatial resolution down to 300 microm with the use
      of the 355 nm wavelength (3rd harmonic of the 1,064 nm Nd:YAG laser wavelength)
      and the pulse energy of 50 mJ. Plant standards and cellulose, doped with multi
      element solution standards, dried and pressed to pellets were used as calibration
      samples. To compensate for signal fluctuations caused by the variation of the
      ablated sample mass 13C was used as a "natural" internal standard. The accuracy
      of the calibration was verified with selected samples analyzed by ICP-MS (high
      pressure digestion, 170 degrees C, 10(7) Pa, HNO3, 2 h) and by laser ablation-ICP
      MS. Recovery rates between 93% (Cu) and 108% (Mn) were obtained. Leaves taken
      from oak trees (Quercus robur) were analyzed.

PMID- 11225837
TI  - Flow injection spectrophotometric determination of ultra trace amounts of oxalic
      acid.
AB  - A new simple, sensitive and rapid catalytic-spectrophotometric method for the
      determination of oxalic acid has been described based on its catalytic effect on
      the redox reaction between dichromate and Brilliant cresyl blue in acidic media
      by means of a flow injection analysis method. The color change of Brilliant
      cresyl blue due to its oxidation was monitored spectrophotometrically at 625 nm.
      The calibration graph was linear in the range of 0.020-4.70 microg/mL oxalic acid
      with a limit of detection 0.005 microg/mL of oxalic acid. The relative standard
      deviation for ten replicate measurements of 0.020 microg/mL and 0.900 microg/mL
      was 2.2% and 1.7%, respectively. No serious interference was identified. Oxalic
      acid was determined in wastewater and in spinach by the proposed method with
      satisfactory results.

PMID- 11225838
TI  - Ferrocenecarboxaldehyde labeled DNA probe for the study on DNA damage and
      protection.
AB  - A ferrocenecarboxaldehyde (FCA) labeled DNA probe is used for the first time in
      the study of DNA damage and protection. The electrochemically active reagent FCA
      was labeled successfully on to a denatured calf-thymus DNA by 1-ethyl-3- (3
      dimethyl-aminopropyl) carbodiimide (EDC). The FCA labeled DNA probe was used to
      hybridize with the sample DNA sequence accumulated on the surface of a graphite
      electrode. The anodic peaks of the FCA bound to the double-stranded DNA (dsDNA)
      by differential pulse voltammetry (DPV) were used for the detection of DNA damage
      and protection. Thiourea, sodium benzoic acid and isopropanol can decrease DNA
      damage by hydroxyl radicals, and their protection efficiencies are discussed.

PMID- 11225839
TI  - Determination of paracetamol (acetaminophen) in different body fluids and organ
      samples after solid-phase extraction using HPLC and an immunological method.
AB  - A solid-phase extraction method routinely used for serum samples was improved and
      applied to the qualitative and quantitative determination of paracetamol in
      different body fluids, e.g. blood, urine, cerebrospinal fluid, synovial fluid,
      vitreous humor, and in tissue samples. A very simple method showed best results:
      Body fluids were mixed with phenacetine as internal standard and phosphate buffer
      (pH 6.8). Then protein was precipitated using acetonitrile. After strong
      centrifugation the supematant was transferred to a preconditioned Bakerbond C18
      SPE-column. Elution with methanol without a prior washing step showed best
      recovery rates. The extracts were investigated using high-performance liquid
      chromatography with ultraviolet detection, a photometrical and an immunochemical
      method.

PMID- 11225840
TI  - Minireview: apoptosis as seen through a lens.
AB  - The lens represents an ideal model system for studying many of the cellular and
      molecular events of differentiation. It is composed of two ectodermally-derived
      cell types: the lens epithelial cells and the lens fibre cells, which are derived
      from the lens epithelial cells by differentiation. Programmed removal of nuclei
      and other organelles from the lens fibre cells ensures that an optically clear
      structure is created, while the morphology of the degenerating nuclei is similar
      to that observed during apoptosis and is accompanied by DNA fragmentation. These
      observations suggest the existence of biochemical parallels between the process
      of lens fibre cell organelle loss and classical apoptosis. For example, proteins
      encoded by the bcl-2 and caspase gene families are expressed in developing lenses
      and nuclear degeneration in lens fibre cells can be inhibited in vivo by
      overexpression of bcl-2 and in vitro by incubation of differentiating lens
      epithelial cell cultures with caspase inhibitors. Thus, the developing lens may
      represent a particularly useful model system for researchers interested in
      apoptosis. In this review, the recent literature pertaining to lens fibre cell
      organelle loss and its relationship to apoptosis is reviewed and possible future
      research directions are suggested.

PMID- 11225841
TI  - Induction of apoptosis by adenovirus E4orf4 protein.
AB  - Adenovirus E4orf4 protein is a multifunctional viral regulator that induces p53
      independent apoptosis in transformed cells, but not in normal cells. E4orf4
      induced apoptosis can occur without activation of known caspases, although E4orf4
      induces caspase activity in some cell lines. The interaction of E4orf4 with a
      specific subpopulation of protein phosphatase 2A (PP2A) molecules that contain B
      subunits, but not with those that contain B' subunits, is required for induction
      of apoptosis. This review suggests the potential use of E4orf4 in cancer therapy,
      and discusses whether E4orf4-induced apoptosis plays a role in the viral life
      cycle. Future research directions are also highlighted.

PMID- 11225842
TI  - The Daxx enigma.
AB  - Several reports describing Daxx and its putative role have emerged without a
      unifying theme. While Daxx has been implicated in apoptosis, it remains unclear
      whether Daxx is pro- or anti-apoptotic, and whether its role in apoptosis is
      direct or indirect. Moreover, whether Daxx plays alternative or additional roles
      in regulating transcription, centromere binding or any number of other activities
      within the cell, is uncertain. The ability of Daxx to interact with a wide
      variety of molecules in yeast-interaction trap systems (Table 1) has allowed for
      this range of speculation. The fact that Daxx contains no significant homology to
      other known proteins has rendered its study all the more challenging.

PMID- 11225843
TI  - Experimental Chagas disease: phagocytosis of apoptotic lymphocytes deactivates
      macrophages and fuels parasite growth.

PMID- 11225844
TI  - Apoptosis and the cell cycle in Xenopus: PMA and MPMA exposure of splenocytes.
AB  - Spontaneous and induced cancers are rare in non-isogeneic or inbred amphibians.
      Neoplastic cells become immortalized through loss of a normal capacity to die by
      apoptosis. Mature lymphocytes of mammals require activation and entry into the
      cell cycle in order to become susceptible to apoptosis. Whether Xenopus
      lymphocytes differ from mammalian lymphocytes in this regard is examined. In
      vitro exposure of PMA, or its analogue, MPMA, to adult splenocytes of Xenopus
      laevis was used to affect apoptosis. Flow cytometric analysis of FITC-Annexin
      V/propidium iodide (PI) fluorescence (apoptosis) and BrdU uptake (DNA synthesis)
      were assayed concurrently in the same lymphocyte population over time.
      Significant increases in apoptotic levels were induced throughout a 72 hour
      period in PMA-treated cells only. Lymphocytes were also separated by size for
      analysis. Several subpopulations of lymphocytes were identified, the most
      interesting of which was small and apoptotic within 4 hours, after PMA exposure.
      PMA-induced DNA synthesis did not become elevated until after 24 hours. "Direct"
      apoptosis, i.e. without cell cycle entry, was found only in these small, mature
      lymphocytes. Since small lymphocytes make up the vast majority of those being
      analyzed, "direct" apoptosis may be a determining mechanism in the resistance to
      neoplasia observed in Amphibia. Cells that die more readily are less likely to
      transform into neoplastic cells.

PMID- 11225845
TI  - Activation of MAD 2 checkprotein and persistence of cyclin B1/CDC 2 activity
      associate with paclitaxel-induced apoptosis in human nasopharyngeal carcinoma
      cells.
AB  - Paclitaxel (Taxol) is a microtubule-interfering agent that induced persistent and
      transient G2/M arrest before apoptosis in human nasopharyngeal carcinoma (NPC)
      cells at high and low concentrations, respectively. In this study, we intended to
      explore the underlying molecular events and found that cellular cyclin B1/CDC 2
      kinase activity was increased and persisted for >6 h upon paclitaxel treatment
      both at high and low concentrations. Furthermore, activation of MAD 2
      checkprotein could account for the loss of cyclin B1 ubiquitination and the
      persistence of cyclin B1/CDC 2 activation in the cases. To investigate the
      involvement of cyclin B1 and MAD 2 activation in paclitaxel-induced apoptosis, we
      introduced affinity-purified anti-cyclin B1 and MAD 2 antibodies into NPC cells
      by electroporation before the further paclitaxel treatment. The antibodies
      against cyclin B1 and MAD 2 indeed attenuated paclitaxel-induced cytotoxicity and
      DNA fragmentation. Our study suggests that activation of cyclin B1/CDC 2 and MAD
      2 were the M-phase events required for paclitaxel-induced apoptosis in NPC cells.
      The dys-regulated cyclin B1/CDC 2 activation could enhance the prometaphase
      progression, but activation of MAD 2 rendered cells inable to exit from the
      metaphase. Under this circumstance, cells were probably going to "mitotic
      catastrophe" and ultimately, destined to apoptosis.

PMID- 11225846
TI  - Caspase-3 activates endo-exonuclease: further evidence for a role of the nuclease
      in apoptosis.
AB  - Single-strand DNase and poly rAase, activities characteristic of endo
      exonuclease, were co-activated in nuclear fractions of HL-60 cells by caspase-3.
      Activation was accompanied by cleavages of large soluble polypeptides (130-185
      kDa) and a 65 kDa inactive chromatin-associated polypeptide related to the endo
      exonuclease of Neurospora crassa as detected on immunoblots. The major products
      seen in vitro were a 77 kDa soluble polypeptide and an active chromatin
      associated 34 kDa polypeptide. When HL-60 cells were induced to undergo apoptosis
      by treating with 50 microM etoposide (VP-16) for 4 hours, 77 kDa and 40 kDa
      polypeptides accumulated in nuclear fractions. Chromatin DNA fragmentation
      activity was also activated in cytosol and nuclear extract either by pre-treating
      the cells in vivo with VP-16 or by treating the cytosol in vitro with caspase-3
      or dATP and cytochrome c. Endo-exonuclease activated by caspase-3 in cytosol
      derived fractions augmented chromatin DNA fragmentation activity in vitro. Endo
      exonuclease is proposed to act in vivo in conjunction with the caspase-activated
      DNase (CAD) to degrade chromatin DNA during apoptosis of HL-60 cells.

PMID- 11225847
TI  - IkappaB/NF-kappaB mediated cisplatin resistance in HeLa cells after low-dose
      gamma-irradiation is associated with altered SODD expression.
AB  - Fractionated gamma-irradiation (15 x 2 Gy in 3 weeks) induces a cellular
      resistance in HeLa cells against cisplatin exposure but not against irradiation.
      The mechanisms underlying this cellular resistance are associated with major
      changes in the TNFR1-dependent transduction pathway. The resistant HeLa/B cells
      exhibit increased levels of NF-kappaB with temporally independent regulation of
      the subunits NF-kappaB50 and NF-kappaB65. Blocking IkappaB degradation by the
      proteasome inhibitor PSI, which abolishes the release of the active NF-kappaB
      protein, induces cell death much more effectively in the parental than in the
      resistant HeLa/B cells. The translocation of NF-kappaB does not seem to be
      affected in a similar manner since masking of the translocation sequence by NF
      kappaB SN50 enhances cisplatin toxicity to the same degree in both cell lines and
      overcomes drug resistance. Changes in upstream signaling are suggested by
      increased sensitivity of the parental HeLa cells to cisplatin in the presence of
      neutralizing anti-TNFR1. In HeLa/B cells, reduced expression of the 50 kDa
      silencer of death domain, SODD, is accompanied by constitutive overexpression of
      a 40-42 kDa SODD-like protein. A possible involvement of SODD in cisplatin
      resistance is discussed, which may shift the balance between life and death in
      the TNF receptor pathway to increased NF-kappaB activation.

PMID- 11225848
TI  - Caspase-dependent and independent cell death in rat hepatoma 5123tc cells.
AB  - The objective of this study was to establish whether apoptosis in 5123tc rat
      hepatoma cells required the caspase-3 dependent pathway. Apoptosis was induced by
      either growth factor deprivation or treatment with a topoisomerase II inhibitor,
      VM26, in the absence or presence of caspase inhibitors (DEVD-fmk, z-VAD-fmk and
      BAF). The results indicated that, although these inhibitors at 10 microM
      concentration completely blocked caspase-3 activity, they had no effect on either
      the rate of cell death or on any other apoptotic features, e.g., chromatin
      condensation, DNA fragmentation, protein cleavage, suggesting that caspase-3 was
      not required to mediate nuclear destruction in these hepatoma cells. At higher
      concentrations, up to 100 microM, z-VAD-fmk and BAF, but not DEVD-fmk, did block
      apoptosis, however, they also caused cell swelling and membrane permeabilization,
      which are the hallmarks of necrotic cell death. Clearly, high concentrations of
      these inhibitors must have interfered non-specifically with other metabolic
      pathways, e.g., z-VAD-fmk at a high concentration blocked protein
      phosphorylation, and caused cell death by a different mechanism.

PMID- 11225849
TI  - Biological and molecular characterization of an ECV-304-derived cell line
      resistant to p53-mediated apoptosis.
AB  - Upregulation of the p53 tumor suppressor protein by infection with a recombinant
      p53 adenovirus resulted in extensive apoptosis in ECV-304 cells and the eventual
      death of almost all the cells. To establish a system to elucidate the molecular
      mechanisms involved in p53-mediated apoptosis of these cells, we established a
      variant of ECV-304 that is resistant to p53-induced apoptosis by repeated
      infections with a recombinant p53 adenovirus. We have designated this variant as
      the DECV cell line (Differentiated ECV-304). DECV cells expressed similar amounts
      of nuclear-localized p53 as ECV-304 cells when infected with recombinant p53
      adenovirus, but in contrast to ECV-304 cells, greater than 95% of DECV cells
      survived and remained viable after 24 hours of infection. In further contrast to
      ECV-304 cells, DECV cells grew less efficiently in soft agar and exhibited
      contact inhibition in growth assays. Moreover, DECV cells formed unusual lattice
      or cyst-like structures in culture and formed lumenal structures indicative of
      epithelial differentiation in three-dimensional collagen matrices, while parental
      ECV-304 cells showed minimal evidence of these cellular behaviors. A comparative
      molecular analysis of gene expression in DECV and ECV-304 cells was conducted by
      cDNA microarray technology. Protocadherin-1 was found to be expressed in DECV
      cells but not in ECV-304 cells, while the Id-3 gene was observed expressed in ECV
      304 cells but not in DECV cells. Moreover, upregulated expression of p53 in ECV
      304 cells induced the EPHB2 (Ephrin) receptor tyrosine kinase and the ephrin-B1
      ligand mRNAs compared to DECV cells treated in the same manner. These data
      demonstrate that a new variant of the ECV-304 cell line, which is resistant to
      p53-mediated apoptosis, exhibits differential gene expression as well as distinct
      cell behaviors as compared to the parental ECV-304 cell line. DECV cells should
      prove to be a useful tool in future studies to elucidate mechanisms of p53
      mediated apoptosis and differentiation.

PMID- 11225850
TI  - Sonoelectroanalysis--an overview.
AB  - The coupling of power-ultrasound with well established but under-exploited
      electrochemical stripping voltammetry has led to the emergence of a powerful new
      analytical technique--sonoelectroanalysis. Where classical electroanalytical
      techniques were plagued with electrode-fouling and/or sensitivity limitations,
      the introduction of ultrasound into the system has given great increases in
      analytical efficiency and substrate applicability, predominantly through enhanced
      mass transport and electrode surface activation. This revitalised analytical
      technology has been applied to a range of modern analytical problems, allowing
      sensitive determination of a wide number of analytes from a variety of otherwise
      hostile matrices, including copper in beer and blood, lead in wine, petrol and
      river bed sediment, vanadium in aqueous media, nitrite in egg and manganese in
      instant tea granules. This paper gives an overview of these recent advances.

PMID- 11225851
TI  - LIGA-electrodes in voltammetric and spectroelectrochemical studies.
AB  - The advantages of lithographic-galvanic (LIGA) fabricated microstructured
      honeycomb electrodes are demonstrated for spectroelectrochemical cells with
      respect to the response time (the time necessary to generate the product in a
      sufficient layer thickness close to the electrode to be detectable by UV-Vis-NIR
      spectroscopy) and to the conversion of the redox system in solution under thin
      layer conditions. Transmission UV-Vis-NIR spectroscopy for several
      electrochemical applications can be performed in a special spectroelectrochemical
      cell based on the LIGA electrode and the two quartz rods, forming the walls of
      the cell and conducting the light beam through the cell. They are limiting the
      diffusion layer at the structured part of the working LIGA electrode. These
      microstructured LIGA-electrodes can be used as well defined models of porous
      electrodes at which redox processes occur under finite diffusion conditions. Such
      electrodes have been successfully used in the voltammetric and
      spectroelectrochemical study of various redox systems in both aqueous and non
      aqueous solvents. The possibility to fabricate the well defined microstructures
      from various organic conducting polymers is demonstrated by the electrochemical
      deposition of polypyrrole in moulded LIGA-forms at high current densities in
      aqueous solutions.

PMID- 11225852
TI  - Basics of temperature pulse voltammetry.
AB  - A new electrochemical technique is presented that allows peak-shaped
      voltammograms to be recorded at local temperature values from room temperature to
      above boiling point. This new method, temperature pulse voltammetry (TPV), is
      analogous to differential pulse voltammetry (DPV), but makes use of temperature
      jumps instead of potential pulses. Fundamentals are presented and potentialities
      demonstrated. As an example, ferrocyanide is investigated using a new kind of
      heated electrode on the basis of screen-printed gold layer structures on low
      temperature cofired ceramics (LTCC) substrates.

PMID- 11225854
TI  - Photocurrent measurements for laterally resolved interface characterization.
AB  - A miniaturized optical set-up based on a CD-ROM player optic was developed for
      LAPS (light addressable potentiometric sensors). A focus of 2.6 microm was
      achieved using this easy to handle device. The lateral resolution of LAPS
      measurements can be improved by using GaAs as the semiconductor material instead
      of Si. The diffusion length of the minority charge carriers was determined to be
      smaller than 3.1 microm. A new method called SPIM (scanning photo-induced
      impedance microscopy) is described. Using this technique, the impedance of thin
      films can be measured with lateral resolution.

PMID- 11225855
TI  - Electrochemical surface analysis with the scanning droplet cell.
AB  - A new electrochemical device, the scanning droplet cell, is presented. Small
      electrolyte droplets are positioned on the sample surface and enable a spatially
      resolved surface analysis or modification. The droplet is simply held by its
      surface tension and, therefore, no surface pretreatment is necessary. According
      to the conventional 3-electrode arrangement all common potentiostatic and
      galvanostatic techniques, e.g. impedance spectroscopy, cyclic voltammetry, or
      current transients of potentiostatic steps, are possible.

PMID- 11225853
TI  - Phenomena at hot-wire electrodes.
AB  - An overview is given describing phenomena at heated microelectrodes where matter
      and heat energy are simultaneously emitted into the solution. With controlled
      electric heating, virtual "quiescent" periods as well as ones with constant
      streaming conditions are found that depend on the heating time. A close look at a
      permanently heated wire reveals a well defined structure with stationary
      concentration, temperature and flow rate profiles. The observed phenomena can be
      utilised for analytical measurements, e.g. with the novel method "Temperature
      Pulse Voltammetry" (TPV).

PMID- 11225856
TI  - Reference electrodes based on conducting polymers.
AB  - Several attempts to produce conducting polymer based all-solid-state reference
      electrodes are presented. Open circuit potential of conducting polymers is redox
      sensitive and Donan equilibrium dependent. Therefore, more sophisticated
      constructions are necessary. Most promising were bilayers composed of conducting
      polymers with different ion-exchanger properties.

PMID- 11225857
TI  - Corrosion protection by the organic metal polyaniline: results of immersion,
      Volta potential and impedance studies.
AB  - Properties of the new polyaniline containing primer CORRPASSIV sealed with two
      different top coats are characterised and compared with top coated samples using
      no or a conventional zinc-rich primer. Measurements were made using scanning
      Kelvin-probe (SKP), electrochemical impedance spectroscopy (EIS), voltammetry and
      analysis of iron and zinc content in electrolytes for testing. Results are
      presented and the powerful corrosion protection using the organic metal is shown.

PMID- 11225858
TI  - Investigation of ion-bombarded conducting polymer films by scanning
      electrochemical microscopy (SECM).
AB  - Scanning electrochemical microscopy (SECM) was used to investigate the effect of
      ion bombardment on thin films of the conducting polymers poly[3-ethoxy-thiophene]
      (PEOT) and poly[ethylenedioxy-thiophene] (PEDT). Bombardment with Ar+-ions
      converts the topmost 30 nm thick layer to an essentially insulating material.
      SECM approach curves as well as two dimensional scans prove the existence of
      regions of different conductivity within the irradiated regions that did not show
      a significant dependence on ion dosage. PEDT layers patterned by ion bombardment
      through microscopic masks are investigated as prototypes of miniaturized printed
      circuit boards that can be formed by galvanic copper deposition onto conducting
      PEDT. Defects in conducting polymer patterns were analyzed by SECM imaging before
      any deposition of copper. Appropriate representations of SECM images for the
      evaluation of this technologically important question are discussed.

PMID- 11225859
TI  - Imaging the activity of nitrate reductase by means of a scanning electrochemical
      microscope.
AB  - Scanning electrochemical microscopy (SECM) was used to characterize immobilized
      nitrate reductase (NaR) from Pseudonomonas stutzeri (E.C. 1.7.99.4). Nitrate
      reductase with membrane fragment was embedded in a polyurethane hydrogel in a
      capillary and solubilized NaR without membrane fragment was covalently coupled to
      a diaminoethyl-cellulose-carbamitate film on glass. After systematic studies of
      possible mediators, SECM feedback imaging of both forms of immobilized NaR was
      accomplished with methylviologen as redox mediator.

PMID- 11225860
TI  - Total determination of metal-binding carbohydrates in plant extracts by using FIA
      with electrochemical detection.
AB  - FIA with pulsed amperometric detection (PAD) is used for the determination of
      metal-binding carbohydrates in plant extracts. Results of direct FIA measurements
      agree very well with those of corresponding HPLC-PAD analyses. The proposed
      method is used to determine total carbohydrates in isolated low-molecular-weight
      fractions of plant roots, which have been obtained after extraction at different
      pH values. The results are compared with those obtained by corresponding metal
      determinations (Ca, Mg, Zn, Mn) by AAS and also with constant potential
      amperometric detection at a copper working electrode. The latter detection mode
      is more sensitive, but less selective for carbohydrates.

PMID- 11225861
TI  - Analysis of illicit drugs by nonaqueous capillary electrophoresis and
      electrochemical detection.
AB  - Nonaqueous capillary electrophoresis (NACE) was applied to the determination of
      illicit drugs. The complete separation of amphetamine, methamphetamine, 3,4
      methylene dioxy amphetamine (MDA), 3,4-methylene dioxy methamphetamine (MDMA),
      mescaline, cocaine and benzoylecgonine was obtained using an acetonitrile based
      buffer solution containing 10 mM sodium acetate and 1 M acetic acid.
      Electrochemical detection using a Pt microdisk electrode set to a potential of
      +1.8 V was found to be selective for MDA, MDMA and mescaline. The detection
      limits for these compounds were in the low ng/mL range which is between 2 and 3
      orders of magnitude lower compared to UV-detection.

PMID- 11225862
TI  - Modified screen-printed electrodes for the investigation of the interaction of
      non-electroactive quinazoline derivatives with DNA.
AB  - Five morpholino-quinazoline derivatives have been investigated voltammetrically
      using a competition with the tris(o-phenanthroline) cobalt(III) redox marker for
      the accumulation at dsDNA modified screen-printed electrodes. An association of
      quinazolines with DNA was observed at the modified electrodes polarized by the
      negative potential of -0.4 V vs. Ag/AgCl. This was confirmed by a potentiometric
      stripping analysis based on the DNA guanine signal. Calibration curves for
      quinazolines within a concentration range of micromol/L were obtained with DP
      voltammetry using 5 x 10(-7) mol/L Co(phen)3(3+) marker. The quinazolines exhibit
      no effect on the DNA complex with the fluorescent thiazole orange derivative TO
      PRO-3. The role of the accumulation potential in the association interaction with
      DNA is discussed.

PMID- 11225863
TI  - Determination of gold using clay modified carbon paste electrode.
AB  - Sorption of gold(III) chlorocomplexes was studied by means of a carbon paste
      electrode modified with montmorillonite. Anionic exchange behavior was found in
      chloride media with low ionic strength. Anionic sorption of [AuCl4]- can be used
      as a preconcentration step to the determination of Au(III). Linear calibration
      dependences were found in the concentration range 4.06 x 10(-6) - 1.22 x 10(-5)
      mol/L Au(III) after 5 min of sorption and in the range 8.12 x 10(-7) - 6. 1 x 10(
      6) mol/L after 10 min of sorption. Interferences of several anions and cations
      were studied. Model samples of table water were analyzed.

PMID- 11225864
TI  - Voltammetric determination of copper at chemically modified electrodes based on
      crown ethers.
AB  - The feasibility of fabricating copper-sensitive chemically modified electrodes
      (CMEs) for trace analysis in aqueous and in 40% (v/v) ethanol-water media was
      investigated. Carbon paste electrodes modified with crown ethers were constructed
      by mixing the crown ethers into a graphite powder-paraffin oil matrix. The
      electrodes so formed were able to bind Cu(II) ions chemically and gave better
      voltammetric responses than the unmodified ones. The crown ethers studied and
      compared were 15-crown-5, benzo-15-crown-5 and dibenzo-18-crown-6. With a 3%
      benzo-15-crown-5 CME, Cu(II) could be quantified at sub-ppm levels by
      differential pulse voltammetry with a detection limit of 0.05 ppm. By
      differential pulse anodic stripping voltammetry Cu(II) could be quantified over
      the range I to 100 ppb. Interference from metal ions like Ni(II), Co(II), Mn(II),
      Fe(II), etc. have also been studied. The method was successfully applied to
      artificial as well as commercial samples of alcoholic beverages.

PMID- 11225865
TI  - Simultaneous determination of Cd, Pb, Cu, Sb, Bi, Se, Zn, Mn, Ni, Co and Fe in
      water samples by differential pulse stripping voltammetry at a hanging mercury
      drop electrode.
AB  - A highly sensitive and selective voltammetric procedure is described for the
      simultaneous determination of eleven elements (Cd, Pb, Cu, Sb, Bi, Se, Zn, Mn,
      Ni, Co and Fe) in water samples. Firstly, differential pulse anodic stripping
      voltammetry (DPASV) with a hanging mercury drop electrode (HMDE) is used for the
      direct simultaneous determination of Cd, Pb, Cu, Sb and Bi in 0.1 M HCI solution
      (pH = 1) containing 2 M NaCl. Then, differential pulse cathodic stripping
      voltammetry (DPCSV) is used for the determination of Se in the same solution. Zn
      is subsequently determined by DPASV after raising the pH of the same solution to
      pH 4. Next, the pH of the medium is raised to pH 8.5 by adding NH3/NH4Cl buffer
      solution for the determination of Mn by DPASV. Ni and Co are determined in the
      same solution by differential pulse adsorptive stripping voltammetry (DPAdSV)
      after adding DMG (1 x 10(-4) M). Finally, 1 x 10(-5) M 2-(5-bromo-2-pyridylazo)-5
      diethylaminophenol (5-Br-PADAP) is added to the solution for the determination of
      Fe by DPAdSV. The optimal conditions are described. Relative standard deviations
      and relative errors are calculated for the eleven elements at three different
      concentration levels. The lower detection limits for the investigated elements
      range from 1.11 x 10(-10) to 1.05 x 10(-9)M, depending on the element determined.
      The proposed analysis scheme was applied for the determination of these eleven
      elements in some ground water samples.

PMID- 11225866
TI  - Microarrayelectrodes for voltammetric and amperometric detection of organic
      pollutants.
AB  - Disk and band shaped microarrayelectrodes (MAE) of gold and carbon have been
      developed. These electrodes can be used for electrochemical detection of
      different organic pollutants in organic and aqueous media. Differential pulse
      voltammetric, cyclic voltammetric and amperometric investigations at these MAE in
      stationary and flowing solutions with selected pesticides, polyaromatic
      hydrocarbons (PAH) and phenols have been carried out.

PMID- 11225867
TI  - Basic investigations on zeolite application for electrochemical analysis.
AB  - Basic investigations on the electrochemical behavior of alumosilicate zeolites
      were conduced in gas atmosphere and aqueous solution using impedance spectroscopy
      under in situ conditions where "zeolitically" bound water molecules are present
      in the channel and cage system. Natural stilbite (STI) and heulandite (HEU),
      zeolites of structure types with the same 4 - 4 = 1 building units, were used for
      these investigations. At a given temperature, well defined water partial
      pressures were applied in the gas atmosphere (in situ conditions) and the effect
      of polar organic molecules on conductivity was investigated. Furthermore, the
      effect of complete water saturation of the channel system on the Arrhenius type
      activation energy of conductivity was investigated in aqueous solution in
      comparison. The ion-exchange behavior of zeolite materials could be monitored
      under these conditions. These results show that, dependent on the different
      parameters affecting the zeolite conductivity behavior, they are applicable in
      the field of electrochemical analysis if these basic results on single crystals
      are transferable to polycrystalline materials.

PMID- 11225868
TI  - Screen-printed copper ion-selective electrodes.
AB  - A simple, low-cost and reproducible method for the mass production of
      potentiometric ion-selective electrodes for copper ions is presented. These
      planar, strip sensors were obtained by screen-printing. The application of pastes
      cured at low temperature allows printing of the sensors on low-cost, plastic
      substrates. The pastes for printing of ion-sensitive thick-film membranes were
      based on copper (1) and copper (II) sulfides. The analytical characteristics of
      the thick-film electrodes were compared. The analytical properties (range of
      determination, sensitivity, selectivity, response time) of the copper (I) sulfide
      based sensors were comparable with those for conventional ion-selective
      electrodes.

PMID- 11225869
TI  - Development of miniaturized potentiometric nitrate- and ammonium selective
      electrodes for applications in water monitoring.
AB  - Mobile analysis with potentiometric sensors is well suited for field
      measurements. Ion-selective electrodes (ISE) based on polymeric membranes for in
      situ determination of nitrate and ammonium contents in ground water, drinking
      water and surface water have been developed. The ISE are integrated in a
      multisensor module (MSM) for monitoring these ions over longer time intervals.
      The receptor is a PVC-membrane with tridodecylammonium nitrate (TDDA) for nitrate
      and nonactine for ammonium-electrodes as ionophores. As plasticizer
      dibutylphthalate (DBT) was used. The main parameters for assessing the efficiency
      of these ISE are presented.

PMID- 11225870
TI  - Calixarenes in analytical and separation chemistry.
AB  - Discovered in the 1940's, [1n]metacyclophanes with the common name calix[n]arenes
      which is derived from for the molecule's shape enjoyed a remarkable interest in
      almost all fields of chemistry since the 1980's, which is highlighted by several
      books [1-8]. Over 50 reviews concerning their synthesis, properties and
      applicabilities were published, many of those with emphasis on organic synthesis
      and structural properties are cited in [P. 5-6 in 2]. Of interest for analytical
      chemists are reviews on calixarenes and the structurally related
      resorcin[n]arenes (or calix[n]resorcarenes) and calixpyrroles concerning
      potentiometric sensors [9-12], chromo- and fluorophores [13, 14], molecular
      switches [15], metal ion binding in solution [16-19], redox properties [20] and
      anion binding [21-24]. Other recent reviews deal with thermodynamic aspects [25],
      organometallic compounds [26], P-containing calixarenes [27-29], as well as
      molecular dynamics modeling [30-33]. It is a vital field with over 200
      publications per year. Therefore, this article presents only selected results on
      complexation, solvent extraction and membrane transport with the emphasis on ion
      and molecular recognition which can be used for analytical purposes, without
      attempting to cover all available references.

PMID- 11225871
TI  - Pre-column (hnu-HPLC) photochemical reaction for the on-line characterization of
      photoproducts using p-aminobenzoic acid as a model substance.
AB  - A special photochemical reactor on the basis of high-pressure resistant reaction
      coils has been constructed, which can be coupled to an HPLC-system before the
      separation column. By means of the so-called "on-line pre-column (hv-HPLC)"
      method, the starting compounds can be irradiated on-line, the conversion products
      formed can be separated and detected subsequently. The efficiency of the proposed
      method was proved by using p-aminobenzoic acid (PABA) as a model substance.

PMID- 11225872
TI  - Influence of process parameters on the composition of gaseous standard mixtures
      of n-propanethiol obtained by thermal decomposition of surface compounds.
AB  - A method for preparation of gaseous standard mixtures of n-propanethiol based on
      thermal decomposition of surface immobilized compounds bonded to silica gel is
      described. On the basis of the experimentally established relationships between n
      propanethiol concentration and generation time, the influence of the mixture
      composition on diluting gas flow rate, decomposition temperature, and surface
      compound bed mass was determined.

PMID- 11225873
TI  - Separation of trace amounts of palladium (II) with crown ether from hydrochloric
      acid and potassium thiocyanate media.
AB  - A new method for the separation of trace amounts of palladium from hydrochloric
      acid and potassium thiocyanate media has been established based on the formation
      of an ion-pair complex of palladium thiocyanate anion Pd(SCN)4(2-) and the
      cationic potassium complex of dicyclohexyl- 18-crown-6 (DC18C6) in chloroform.
      The effect of various factors (solvent, crown ether, potassium thiocyanate,
      hydrochloric acid, reagent concentration, shaking time, phase volume ratio,
      composition of the extracted species, foreign ions, etc.) on the extraction and
      back-extraction of palladium has been investigated. The method can be combined
      with subsequent FAAS determination of palladium. The procedure was applied to
      determine palladium traces in chloroplatinic acid and rhodium chloride.

PMID- 11225874
TI  - Determination of trace metals in high purity gold.
AB  - The possibility of using ETAAS or ICP-AES for the determination of trace amounts
      of Ag, Bi, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Pd, Pt and Sb in pure gold is
      investigated. The influence of the matrix element on the atomization of the trace
      analytes is studied and optimal instrumental parameters are defined. An
      analytical method based on matrix element reductive separation followed by
      spectrometric determination of trace analytes is proposed as an alternative for
      the analysis of high purity gold. Advantages and disadvantages of proposed
      analytical procedures from the viewpoint of achieved repeatability,
      reproducibility and detection limits and of the duration of analysis are
      discussed.

PMID- 11225875
TI  - Determination of uranium in tap water by ICP-MS.
AB  - A fast and accurate procedure has been developed for the determination of uranium
      at microg L(-1) level in tap and mineral water. The method is based on the direct
      introduction of samples, without any chemical pre-treatment, into an inductively
      coupled plasma mass spectrometer (ICP-MS). Uranium was determined at the mass
      number 238 using Rh as internal standard. The method provides a limit of
      detection of 2 ng L(-1) and a good repeatability with relative standard deviation
      values (RSD) about 3% for five independent analyses of samples containing 73
      microg L(-1) of uranium. Recovery percentage values found for the determination
      of uranium in spiked natural samples varied between 91% and 106%. Results
      obtained are comparable with those found by radiochemical methods for natural
      samples and of the same order for the certified content of a reference material,
      thus indicating the accuracy of the ICP-MS procedure without the need of using
      isotope dilution. A series of mineral and tap waters from different parts of
      Spain and Morocco were analysed.

PMID- 11225876
TI  - Analysis of poly-beta-hydroxybutyrate in environmental samples by GC-MS/MS.
AB  - Application of gas chromatography-mass spectrometry (GC-MS) can significantly
      improve trace analyses of compounds in complex matrices from natural environments
      compared to gas chromatography only. A GC-MS/MS technique for determination of
      poly-beta-hydroxybutyrate (PHB), a bacterial storage compound, has been developed
      and used for analysis of two soils stored for up to 319 d, fresh samples of
      sewage sludge, as well as a pure culture of Bacillus megaterium. Specific
      derivatization of beta-hydroxybutyrate (3-OH C4:0) PHB monomer units by N-tert
      butyl-dimethylsilyl-N-methyltrifluoracetamide (MTBSTFA) improved chromatographic
      and mass spectrometric properties of the analyte. The diagnostic fragmentation
      scheme of the derivates tert-butyldimethylsilyl ester and ether of beta
      hydroxybutyric acid (MTBSTFA-HB) essential for the PHB identification was shown.
      The ion trap MS was used, therefore the scan gave the best sensitivity and with
      MS/MS the noise decreased, so the S/N was better and also with second
      fragmentation the amount of ions increased compared to SIM. The detection limit
      for MTBSTFA-HB by GC-MS/MS was about 10(-13) g microL(-1) of injected volume,
      while by GC (FID) and GC-MS (scan) it was around 10(-10) g microL(-1) of injected
      volume. Sensitivity of GC-MS/MS measurements of PHB in arable soil and activated
      sludge samples was down to 10 pg of PHB g(-1) dry matter. Comparison of MTBSTFA
      HB detection in natural soil sample by GC (FID), GC-MS (scan) and by GC-MS/MS
      demonstrated potentials and limitations of the individual measurement techniques.

PMID- 11225877
TI  - Combined protocol for the analysis of polycyclic aromatic hydrocarbons (PAHs) and
      polychlorobiphenyls (PCBx) from sediments using focussed microwave assisted (FMW)
      extraction at atmospheric pressure.
AB  - A microwave-assisted protocol has been developed using focussed microwaves at
      atmospheric pressure for the extraction of PAHs and PCBs from sediments. It
      combines extraction and purification assisted by microwaves. This protocol has
      been applied to the quantification of 12 individual PAHs, 8 individual PCBs and 8
      PCB coeluted mixtures from two Standard Reference Materials and one natural
      sediment. The results for both classes of compounds (PAHs and PCBs) are good in
      terms of recoveries, which are always greater than 70% and in most cases around
      100%. The reproducibility is also good with coefficients of variation below 10%
      in most cases. This protocol has the great advantage of saving time, the time
      dedicated to the preparation / extraction assisted by microwaves being reduced to
      less than half an hour.

PMID- 11225878
TI  - Spectroelectrochemical investigation of direct electron transfer between resting
      horseradish peroxidase and its oxidation states promoted by DNA.
AB  - Direct electron transfer between resting horseradish peroxidase (HRP) and its
      oxidation states was observed at a gold mesh electrode in a
      spectroelectrochemical cell in the presence of DNA. The conversion between HRP
      and the oxidized species induced electrochemically was found to be reversible and
      parallel to that initiated chemically. DNA played an important role as electron
      carrier and promoted the electron transfer between HRP and the electrodes.
      Voltammetric results and CD spectra indicated an interaction between HRP and DNA.
      Moreover, the secondary structure of HRP was slightly disturbed upon mixing with
      DNA. The direct spectroelectrochemistry of HRP at a gold mesh electrode presented
      new information on its bioelectrochemical characteristics.

PMID- 11225879
TI  - Amperometric biosensor based on D-aminoacid oxidase for the R-perindopril assay.
AB  - A new amperometric biosensor based on D-aminoacid oxidase is described for the
      assay of R-perindopril. R-perindopril can be determined in the 400-20 nmol/L
      concentration range; the detection limit is 10 nmol/L. The selectivity was
      checked with S-perindopril, D- and L-proline, and polyvinylpyrrolidone. The main
      interfering species was D-proline. An automated system for the assay of R
      perindopril based on the concept of flow injection with an amperometric biosensor
      (based on D-aminoacid oxidase) as detector is also described. The system is
      suitable for the on-line monitoring of R-perindopril at a sampling rate of 72
      samples/h, in the linear range: 100 nmol/L -20 nmol/L with an RSD better than
      0.09% (n = 10).

PMID- 11225880
TI  - Determination of 'arsenosugars' in algae with anion-exchange chromatography and
      an inductively coupled plasma mass spectrometer as element-specific detector.
AB  - The retention behavior of four naturally occurring dimethylarsinoylribosides with
      -CH2-CHOH-CH2X (X = OH, HO3POCH2CHOHCH2OH, SO3H, OSO3H) as aglycones, of arsenous
      acid, arsenic acid, methylarsonic acid, and dimethylarsinic acid was investigated
      on a Hamilton PRP-X100 anion-exchange column with aqueous solutions of ammonium
      dihydrogen phosphate (20 mmol/L) in the pH range of 3.8-9.0 as mobile phase. A HP
      4500 inductively coupled plasma mass spectrometer (ICP-MS) served as arsenic
      specific detector. The influence of pH, temperature, and the concentration of
      methanol in the mobile phase on the retention times of these arsenic compounds
      was explored. An aqueous 20 mM ammonium dihydrogen phosphate solution at pH 5.6
      at a column temperature of 40 degrees C was considered optimal as it allowed the
      separation of seven of the arsenic compounds within 16 min. Only arsenous acid
      and the ribose with the glycerol aglycone have overlapping signals with both
      migrating almost with the solvent front. At a concentration of 0.50 ng As mL(-1)
      the relative standard deviations (n = 3) of the signal areas of the eight arsenic
      compounds was in the range from 3.5 to 8.1%. The linear calibration curves (peak
      areas) from 0.5 to 10 ng/mL had correlation coefficients > 0.997. Extracts
      obtained from the brown algae Fucus spiralis and Halidrys siliquosa were
      chromatographed under the optimized conditions. Both species contained the
      sulfate riboside as the major arsenic compound (approximately 55% of total
      extractable arsenic) together with the sulfonate- and phosphate riboside. Arsenic
      acid was a significant constituent of Halidrys siliquosa (approximately 6.5%),
      but was not detected in Fucus spiralis.

PMID- 11225881
TI  - Phase-selective a.c. adsorptive stripping voltammetry of lumazine on a hanging
      mercury drop electrode.
AB  - The electrochemical behavior of lumazine (LMZ), an important antibacterial agent,
      has been studied at the hanging mercury drop electrode (HMDE). The nature of the
      process taking place at the HMDE was clarified. Its adsorption behavior at HMDE
      has been studied by using a.c and cyclic voltammetry (CV). Both the molecule and
      its reduced product appeared to be adsorbed at the surface of the electrode.
      Controlled adsorptive accumulation of LMZ on the HMDE provides the basis for the
      direct stripping measurement of that compound in the subnanomolar concentration
      level. Experimental and instrumental parameters for the quantitative
      determination were optimized. Phase-selective a.c voltammetry provided the best
      signal and gave a detection limit of 0.15 microg L(-1) (9.0 x 10(-10) mol/L) LMZ
      in aqueous solution. Molecules or ions which may interfere were studied.

PMID- 11225882
TI  - Automation of the GC/MS analysis of mineral oil contaminations in water.
AB  - An automation of the sample preparation and analysis of mineral oil
      contaminations in water was developed. The automated sample preparation was
      carried out according to ISO/DIS 9377-4 [1]. The standard is applicable to the
      determination of hydrocarbons in the boiling range of n-decane (n-C10) up to n
      tetracontane (n-C40) by GC. Extraction of the sample and clean-up of the extract
      were performed by an autosampler with a movable head which is capable of carrying
      different syringes for gas and liquid handling. A GC/MS-system with a programmed
      temperature vaporizing (PTV) injector including the possibility of large volume
      injections (LVI) was employed for the analysis. The recovery of analytes was
      101.8%, the repeatability 2.9% relative standard deviation (RSD). The linear
      range covered 0.3 to 40 mg/L oil but may be larger since no higher concentrations
      were measured. With an FID, being the detector of choice mentioned in the
      standard, it should be possible to achieve at least four orders of magnitude in
      the linear range. The limit of determination was found to be 0.3-0.4 mg/L, the
      limit of detection 0.1-0.2 mg/L [2]. Measurements of spiked deionized,
      bidistilled water and spiked water from a lake confirmed the accuracy of the
      analysis. Due to automation and miniaturization of the analysis it is possible to
      economize time and chemicals without loss of precision and accuracy.

PMID- 11225883
TI  - A factorial design for optimizing a flow injection analysis system.
AB  - The use of a factorial design for the response exploration of a flow injection
      (FI) system is described and illustrated by FI spectrophotometric determination
      of paraquat. Variable response (absorbance) is explored as a function of the
      factors flow rate and length of the reaction coil. The present study was found to
      be useful to detect and estimate any interaction among the factors that may
      affect the optimal conditions for the maximal response in the optimization of the
      FI system, which is not possible with a univariate design. In addition, this
      study showed that factorial experiments enable economy of experimentation and
      yield results of high precision due to the use of the whole data for calculating
      the effects.

PMID- 11225884
TI  - Studies on the potentiometric thallium(III)-selective carbon paste electrode and
      its possible applications.
AB  - Construction, performance characteristics and applications of a carbon paste
      thallium(III) ion-selective electrode are described. The electrode, which is
      based on ion-associate compounds formed between cetylpyridinium and
      chlorothallate(III) complexes dissolved in tricresyl phosphate as pasting liquid,
      showed near-Nernstian response over the concentration range of 5.8 x 10(-6) - 2.9
      x 10(-3) mol/L. Potentiometric titrations of thallium(III) with cetylpyridinium
      chloride were affected by higher concentrations of excess halides, probably due
      to the formation of higher halogenothallates.

PMID- 11225885
TI  - Electrothermal atomic absorption spectrometric determination of trace elements in
      high-purity silver after total and partial reductive separation of the matrix.
AB  - A sensitive and reliable ETAAS determination of metal traces in high purity
      silver after total (Bi, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb) and partial (As, Hg, Sb,
      Se) separation of the matrix with ascorbic acid is described. The temperature
      program is optimized for analyte determination in ascorbic acid media and in 1%
      silver solution.

PMID- 11225886
TI  - Improvement of direct determination of trace nickel in environmental samples by
      diffuse reflection spectroscopy using chromaticity characteristics.
AB  - Cellulose and chromaton-N-super as solid supports for direct determination of the
      immobilized nickel complexes with dimethylglyoxime and benzyldioxime by diffuse
      reflection spectroscopy were compared. The advantage of chromaton-N-super with
      use of benzyldioxime is shown. Detection limit is 0.02 microg/mL. The proposed
      method was applied for the analysis of soil.

PMID- 11225887
TI  - Capillary electrophoretic determination of dithiocarbamates and ethyl xanthate.
AB  - A simple and sensitive capillary electrophoretic method was developed for the
      separation and determination of sodium methyldithiocarbamate (metham), manganese
      ethylenebisdithiocarbamate (maneb) and ethyl xanthate in boric acid buffer by
      direct UV absorbance detection at lambda = 254 nm. The separation is dependent on
      pH and nature of the buffer. The detection limits (S/N = 3) are 1.7 x 10(-6)
      mol/L for ethyl xanthate, 1.3 x 10(-6) mol/L for metham and 2.1 x 10(-6) mol/L
      for maneb. The method has been successfully applied to the analysis of wheat
      samples spiked with maneb and in a commercial sample.

PMID- 11225888
TI  - Three new methods for male contraception.
AB  - The methods devised for male contraception are meagre. In the current
      communication, we review 3 recently developed methods applied for male
      contraception: testicular suspension, polyester-induced azoospermia and prolactin
      injection. The testicle was suspended in the superficial inguinal pouch close to
      the scrotal neck using 2 methods: stitch and ball. The azoospermic effect of the
      polyester sling seems to be due to 1) creation of electrostatic field across the
      intrascrotal structures, and 2) disordered thermoregulation. Prolactin
      administration, as a contraceptive method is efficient and safe and has the
      potential to be developed as a male contraceptive. The effect of the above
      mentioned 3 methods is reversible. These methods, especially testicular
      suspension and polyester suspensors, are simple and easily applicable and were
      well acceptable by the subjects.

PMID- 11225889
TI  - The effects of androgen on penile reflex, erectile response to electrical
      stimulation and penile NOS activity in the rat.
AB  - AIM: To investigate the effects of androgen on penile erection through the reflex
      arc and penile corpus cavernosum, and study the respective roles of testosterone
      (T) and dihydrotestosterone (DHT) in penile erection in rats. METHODS: Male
      Sprague-Dawley rats were castrated and implanted with silastic brand silicone
      tube containing T or DHT, with or without daily injections of a 5alpha-reductase
      inhibitor, MK-434. The penile reflex, erectile response to electrical stimulation
      (ES) of the cavernous nerves and penile nitric-oxide synthase (NOS) activity were
      observed under varying androgenic status. RESULTS: Penile reflex erection in the
      rat was, on the whole, related to serum T levels though the number of glans
      engorgements was not. The number of cups and flips was significantly decreased by
      castration, and restored to the control level by T supplementation. Erectile
      response to ES and NOS activity in penile tissue was also related to serum T
      level. T administered together with a 5alpha-reductase inhibitor no longer
      restored the number of reflex erection, erectile responses to ES and NOS activity
      in the corpus caveenosum. CONCLUSION: Androgen influenced the penile reflex arc,
      corpus cavernosum, and the perineal striated muscles. In reflex erection,
      erectile response to ES and penile NOS activity in the rat, T seems to be first
      converted to DHT, the more active androgen modality.

PMID- 11225890
TI  - Protective effect of Prostane in experimental prostatic hyperplasia in rats.
AB  - AIM: Prostane, a polyherbal formulation, was evaluated for its efficacy on 5alpha
      reductase inhibition, alpha-adrenergic antagonistic activity and testosterone
      induced prostatic hyperplasia. METHODS: 5alpha-reductase inhibition was evaluated
      using rat prostate homogenate as an enzyme source. Adrenergic antagonistic
      activity was evaluated using isolated rat vas deferens. Experimental prostatic
      hyperplasia was induced in rats by giving testosterone 3 mg/kg sc for 21 days.
      RESULTS: Prostane dose-dependently inhibited 5alpha-reductase activity and
      exhibited alpha-adrenergic antagonistic activity. Treatment with Prostane at 250,
      500 and 750 mg/kg body wt, po for 21 days significantly reduced the prostatic
      weight, the epithelial height and the stromal proliferation in experimental
      prostatic hypertrophy. CONCLUSION: Prostane is effective in the treatment of
      experimental prostatic hypertrophy in rats and may be passed on to clinical
      trials on benign prostatic hypertrophy after necessary toxicological evaluations.

PMID- 11225891
TI  - Apoptosis in rat erectile tissue induced by castration.
AB  - AIM: To investigate the effect of androgen on the structure of corpus cavernosum.
      METHODS: Thirty mature rats were randomized into 3 groups, i.e., simple
      castration, castration with testosterone (T) supplementation and sham-operated
      controls. One week after operation, the animals were sacrificed and corpora
      cavenosa harvested. Apoptosis was detected with the in situ end labeling (ISEL)
      techniques and DNA fragment analysis. RESULTS: The apoptotic rate was 4.19% in
      the simple castrated rats, 0. 2% in castrated rats supplemented with T and 0.14%
      in the controls. Significant difference was found between the simple castrates
      and other two groups (P < 0.01). When comparing the T-supplementation group with
      the controls, there was no statistical difference (P > 0.05). CONCLUSION:
      Castration induced apoptosis in rat corpus cavernosum, that could be prevented by
      T supplementation. It suggests that androgen plays an important role in
      maintaining the structure of corpus cavernosum.

PMID- 11225892
TI  - Proliferation of exogenously injected primordial germ cells (PGCs) into busulfan
      treated chicken embryos.
AB  - AIM: This study was designed to investigate the effect of busulfan treatment on
      the proliferation of chicken primordial germ cells (PGCs) in vivo, focusing on
      the preferential settlement of PGCs onto the germinal ridges of chicken embryos.
      METHODS: Busulfan (250 ng/egg) was injected into the egg white of freshly
      oviposited fertilized eggs, which were then incubated. Embryonic development and
      viability were examined, and exogenous PGCs collected from embryonic blood
      vessels were injected into the germinal crescent region of recipient embryos. The
      number of PGCs resided onto germinal ridges of the right and left sides were
      compared. RESULTS: Busulfan had a slight harmful effect on the embryo viability
      and the PGCs proliferation. The number of PGCs resided onto the left side of
      germinal ridges was slightly higher as compared with the right side. CONCLUSION:
      Busulfan suppressed the viability of embryos and the proliferation of endogenous
      PGCs in the recipient embryos. However, the number of exogenous PGCs proliferated
      was higher in embryos treated with busulfan than those without busulfan. Data
      also suggest the possibility of a preferential residence of PGCs toward the left
      side of the germinal crescent region as compared with the right, which may be due
      to a more advanced functional development of the left gonad than the right.

PMID- 11225893
TI  - Studies on LH modulated 8kDa peptide involved regulation of testosterone
      production in rat Leydig cells.
AB  - AIM: To demonstrate the role of the 8 kDa peptide in regulation of testosterone
      production by rat Leydig cells. METHODS: A peptide similar to 8 kDa peptide
      purified from immature rat Leydig cells was isolated and purified from rat lung
      cytosol. Immunological and structural similarity between the peptides purified
      from lung and Leydig cells was established by Western blot and tryptic map
      comparison respectively. RESULTS: Addition of the 8 kDa peptide 10, 50, 100, and
      150 microg decreased the production of testosterone in Leydig cells dose
      dependently. But the addition of the peptide 150 microg along with hCG had no
      effect on hCG-stimulated increase in testosterone production. CONCLUSION: In
      vitro addition of the peptide purified from lung cytosol to adult rat Leydig
      cells resulted in a concentration-dependent decrease in basal testosterone
      production although it had no effect on hCG-stimulated testosterone production.

PMID- 11225894
TI  - Preparation and identification of activity of anti-HPV-6b/11E1 universal ribozyme
      -Rz1198 in vitro.
AB  - AIM: To study the preparation and cleavage activity of Rz1198 directed against
      HPV-6bE1 and HPV-11E1 (HPV-6b/ 11E1) transcripts in vitro. METHODS: HPV-6b/11E1
      gene fragments were cloned into T-vector under the control of T7 promoter. 32P
      labeled HPV-6b/11E1 transcripts as target-RNAs were transcribed in vitro and
      purified by PAGE. Rz1198 gene designed as a universal ribozyme for both HPV
      6b/11E1 transcripts was cloned into vector p1.5 between 5'-cis-Rz and 3'-cis-Rz.
      32P-labeled Rz1198 transcript was gel-purified, incubated with target-RNAs at
      different conditions and autoradiographed after denaturing gel-electrophoresis.
      RESULTS: Rz1198 was active at 37 degrees C. The optimal temperature was 50
      degrees C. For HPV-6bE1, km = 12.2 nmol/L, kcat = 0.18 min(-1); For HPV-11E1, km
      = 14.7 nmol/L, kcat = 0.14 min(-1). All these revealed that the design of Rz1198
      was correct. It could be a universal ribozyme for the two substrates--HPV-6bE1
      and HPV-11E1 transcripts. CONCLUSION: Rz1198 prepared in vitro possesses the
      perfect specific catalytic cleavage activity. It leads to the expectation that,
      in the future, it will be possible to develop a new nucleic acid drug from Rz1198
      which can efficiently inhibit the replication of HPV-6b/11 DNA in vivo.

PMID- 11225895
TI  - Chronic effect of endosulfan on the testicular functions of rat.
AB  - AIM: To find out the toxic effect of endosulfan on the testicular function of
      pubertal rats. METHODS: Male rats of pubertal age were orally administered
      endosulfan at a dose of 1.0 mg/kg body weight for 30 days. Twenty-four hours
      after the last treatment, the rats were sacrificed and the testis, epididymis,
      seminal vesicles and ventral prostate were removed and weighed. A 10% testicular
      homogenate was prepared for biochemical estimations. RESULTS: In endosulfan
      treated rats, there were a reduction in the body weight and the weights of testis
      and accessory sex organs, a decrease in the testicular lactate and pyruvate
      activities, and in the testicular DNA and RNA concentrations, whereas the
      testicular protein concentration was slightly increased; the specific activity of
      testicular steroidogenic enzyme, 3beta-OH-steroid dehydrogenase and the ascorbic
      acid level were decreased, which were correlated with a decrease in
      steroidogenesis. The lysosomal enzyme acid phosphatase and brush-border enzyme
      alkaline phosphatase activities were also decreased in the testis of treated
      rats. CONCLUSION: In pubertal rats, endosulfan treatment inhibits the testicular
      functions.

PMID- 11225896
TI  - Erectile dysfunction: on the efficacy of a phosphodiesterase inhibitor with
      concurrent sex therapy.

PMID- 11225897
TI  - Erectile dysfunction: on the efficacy of a phosphodiesterase inhibitor in
      patients with multiple risk factors.

PMID- 11225898
TI  - Ambulatory urodynamic monitoring of external urethral sphincter behavior in
      chronic prostatitis patients.
AB  - AIM: To study the behavior of external urethral sphincter in chronic prostatitis
      (CP) patient under natural filling. METHODS: Twenty-one CP patients and 17 normal
      volunteers were involved in the study. Both the patients and volunteers underwent
      ambulatory urodynamic monitoring (AM) and conventional medium filling cystometry
      (CMG). Urodec 500 was used for AM and Menuet for CMG. AM findings from CP
      patients were compared with those from normal volunteers, and the results from AM
      were compared with those from CMG. RESULTS: In AM, the resting and voiding
      external urethral sphincter (EUS) pressures and maximum urethral closure
      pressures (MUCP) were significantly higher in CP patients [(121.5 +/- 10.3) and
      (85. 6 +/- 3.5) cm water, respectively] than in normal volunteers [(77.6 +/-
      11.4) and (10.3 + 1.6) cm water, respectively)]. CONCLUSION: The behavioral
      changes of EUS in CP patients included spasm and instability of EUS, which were
      demonstrated using AM under natural filling; the findings were also in accord
      with the results of CMG.

PMID- 11225899
TI  - Male reproductive health research needs and research agenda: Asian and Chinese
      perspective.
AB  - Research that addresses male reproductive health should assist in the development
      of reproductive health programmes and policy; identify and test new leads in male
      contraceptive technology; establish effective male involvement initiatives which
      are likely to have a positive impact on the reproductive health of men and women;
      guide the allocation of health care resources to ensure cost-effectiveness of
      interventions; generate new knowledge, develop diagnostic technology in
      reproductive health and offer optimal treatment/care regimens. In considering the
      needs and demands of male reproductive health research in Asia and the Pacific,
      the following six research topics are recommended as the priority research areas:
      male contraceptive technology; male reproductive health behaviour and male
      adolescent reproductive health; male reproductive aging including male menopause
      and other diseases; male RTIs, STDs, HIV/AIDS; prevalence, management and
      prevention of male infertility; environment and semen quality and other male
      reproductive problems. One of the major challenges now facing us is the
      elaboration of a comprehensive, yet realistic male reproductive health research
      agenda that reflect the needs and demands of Asian developing countries. To this
      end, to make use of an interdisciplinary approach is of strategic importance. The
      most creative insights and productive leads are likely to emerge from a research
      team that is interdisciplinary especially in the field of reproductive health.

PMID- 11225900
TI  - One and the same androgen for all? Towards designer androgens.
AB  - The introduction of designer oestrogens as a treatment modality in hormone
      replacement in women has invited to consider the concept of compounds with
      selective androgenic effects for male hormone replacement therapy. The full
      spectrum of the actions of testosterone may not be necessary of even undesired
      for certain indications for testosterone treatment. To define for what
      indications certain androgenic properties are desired and undesired more insight
      in basic androgen (patho)physiology is required. There is convincing evidence
      that aromatization of androgenic compounds to oestrogens might be an advantage
      for maintenance of bone mass and it might also mitigate negative effects of
      androgens on biochemical parameters of cardiovascular risks; the potentially
      negative effects of oestrogens on prostate pathology in ageing men needs further
      elucidation. While the role of dihydro-testosterone (DHT) for the male sexual
      differentiation and for pubertal sexual maturation is evident, its role in mature
      and ageing males seems less significant or may even be harmful. It is, however,
      of note that a negative effect of DHT on prostate pathophysiology is certainly
      not proven. For male contraception a progestational agent with strong androgenic
      properties might be an asset. For most of the androgenic actions the critical
      levels of androgens are not well established. The latter is relevant since the
      large amount of androgen molecules required for its biological actions (as
      compared to oestrogens) is an impediment in androgen replacement modalities.
      There may be room for more biopotent androgens since delivery of large amounts of
      androgen molecules to the circulation poses problems for treatment modalities.

PMID- 11225902
TI  - Current challenges of andrology.
AB  - As President of the International Society of Andrology, it gives me great
      pleasure to congratulate the Asian Society of Andrology for its initiative in
      founding the Asian Journal of Andrology. In doing so, I also send my best wishes
      for the success of this important journal in spreading the knowledge of andrology
      throughout the most populous continent in the world. This new journal appears at
      a very timely moment, at the turn of the millennium and at a time when andrology
      is receiving the recognition amongst medical specialities that it deserves. In
      conclusion, I would like to call on all Asian andrologists to support their
      journal and to work to improve the reproductive health of men.

PMID- 11225901
TI  - Approaches to post-testicular contraception.
AB  - The induction of infertility in males of several species through epididymal
      interference is more difficult to achieve by reduction of the amounts of
      epididymal secretions (eg alpha-glucosidase, L-carnitine) or immunological
      interference with secreted proteins (eg D/E, P34H, P26h) than by direct actions
      of drugs on sperm function (eg inhibition of glyceraldehyde 3-phosphate
      dehydrogenase by chloro-compounds). The latter approach holds promise for mankind
      as human sperm are susceptible to glycolytic inhibition. Future contraceptive
      developments may arise from production of targeted inhibitors, research on the
      displacement of sperm proteins in the epididymis and interference with sperm
      plasma membrane ion channels.

PMID- 11225903
TI  - Recent advancement in diagnosis of vasculogenic impotence.
AB  - Several dynamic tests with vasoactive drugs are available for evaluating penile
      vascular inflows and outflows, ranging from simple pharmacologic test to more
      invasive radiologic sets. However, there is still no perfect single test to
      reflect the penile vascular flow. All possible efforts should be exerted to get
      the greatest erectile effect to avoid an underestimation of blood flow to the
      corpora due to incomplete relaxation of the trabecular smooth muscle.
      Appreciation of the type and frequency of anatomical variations and potential
      collateral routes is important in interpreting penile arterograms and in
      evaluating the hemodynamic significance of suspected arterial disease. Choice of
      the vascular tests should always depend on the purpose of testing.

PMID- 11225904
TI  - Advancement in biochemical assays in andrology.
AB  - Determination of markers of sperm function, accessory sex gland secretion and
      silent male genital tract inflammation is of considerable diagnostic value in the
      evaluation of male infertility. The introduction of biochemical tests into the
      analysis of male factor has the advantage that standardized assays with a
      coefficient of variation characteristic of clinical chemistry are performed, in
      contrast to biological test systems with a large variability. Biochemical
      parameters may be used in clinical practice to evaluate the sperm fertilizing
      capacity (acrosin, aniline blue, ROS), to characterize male accessory sex gland
      secretions (fructose, alpha-glucosidase, PSA), and to identify men with silent
      genital tract inflammation (elastase, C'3 complement component, coeruloplasmin,
      IgA, IgG, ROS).

PMID- 11225905
TI  - Effects of castration and testosterone replacement on veno-occlusion during
      penile erection in the rat.
AB  - AIM: To determine if androgens directly regulate veno-occlusion or if androgens
      act indirectly to maintain the penile structures which control outflow. METHODS:
      Using CASTRATE and TESTO rats, measurement was made of mean arterial pressure
      (MAP), intracavernosal pressure (CCP), and intracavernosal flow (CCF) during
      erection resulting from stimulation of the autonomic innervation of the penis.
      CCP and CCF were also measured during saline infusion into the cavernosal sinuses
      before and after treatment with sodium nitroprusside (SNP, a nitric oxide donor
      drug) to fully relax cavernosal smooth muscle. Penile tissue was also collected
      to measure the content of alpha actin and proline and hydroxyproline to determine
      if brief withdrawal of androgenic support led to changes in the number of smooth
      muscle cells or the collagen content of the tissue. RESULTS: Infusion of saline
      into the cavernosal sinuses demonstrated that veno-occlusion was defective in
      CASTRATE rats while veno-occlusion was fully functional in TESTO animals.
      Furthermore, veno-occlusion could be induced in CASTRATE rats if they were first
      treated with SNP. This observation suggests that failure of veno-occlusion in the
      CASTRATE rats is due to a deficiency in the production of NO resulting in a
      reduction in the degree of relaxation of the penile smooth muscle. The
      measurements of smooth muscle a actin and proline and hydroxyproline content of
      collagen showed that both were unaffected by castration and that the basic
      structure of the penis did not degenerate after one week without androgenic
      support. CONCLUSION: These results can be interpreted to mean that androgens
      control the veno-occlusive mechanism indirectly via a NO dependent mechanism and
      not by maintaining the structures of the penis which are essential to veno
      occlusion.

PMID- 11225906
TI  - Morphological changes of spermatozoa in proximal vas deferens after vasectomy.
AB  - AIM: To investigate the morphological changes of spermatozoa in the proximal vas
      deferens after vasectomy. METHODS: Proximal vas deferens fluids were collected
      from 79 fertile men (group A) and 64 vasectomized men (group B) during the
      operations of vasectomy or vasovasostomy. Sperm morphology in the proximal vas
      deferens was analyzed after staining with the modified Papanicolaou method.
      RESULTS: The percentage of spermatozoa with a normal oval head from group B (50.
      7% +/- 21.7%) was significantly lower than that of group A (75.2% +/- 11.1%). The
      data in group A was similar to those of normal semen and therefore represents the
      physiological condition of the proximal vas deferens sperm of fertile men. There
      were no significant differences in the percentages of normal oval heads in group
      B with the time since vasectomy. CONCLUSION: After vasectomy, the spermatozoa in
      the proximal vas deferens and epididymis were continuously degenerating and being
      replenished by spermatozoa coming from testis. The obvious morphological
      degeneration occurred in the sperm tail and spermatozoa with a small oval head
      and amorphous heads were increased.

PMID- 11225907
TI  - Urinary follicle stimulating hormone can be used as a biomarker to assess male
      reproductive function.
AB  - AIM: To develop an algorithm for use in population-based studies to assess
      testicular function by measurements of total urinary follicle stimulating hormone
      (FSH). METHODS: Total concentrations of urinary FSH were measured in a group of
      44 men at the University of California, Davis (UCD) and were compared to FSH
      measurements in serum. On the basis of these and other published data, a urinary
      FSH value of >2 ng/mg creatinine (Cr) was selected as the cutoff point to
      identify men with elevated serum FSH ( > 12 IU/L) or low sperm counts ( < 20
      million/mL). RESULTS: The sensitivity and specificity of this algorithm for
      detecting elevated serum FSH in a group of 58 agricultural workers in the People'
      s Republic of China were 100% and 50%, respectively. The sensitivity and
      specificity of this algorithm for detecting low sperm counts in a population of
      105 infertility patients at UCD were 58 % and 76 %, respectively. CONCLUSION:
      This test may have particular value in identifying populations with no evidence
      of testicular toxicity, and in which labor-intensive semen studies may not be
      feasible.

PMID- 11225908
TI  - The contribution of Asian scientists to global research in andrology.
AB  - AIM: To present a personal account of the involvement of the World Health
      Organization (WHO) in the collaborative development in Asia of those areas of
      andrology concerned with male contraception and reproductive health. METHODS: The
      andrology training through workshops and institution support undertaken by the
      WHO Human Reproduction Programme (HRP) and how they contributed to the
      strengthening of andrology research in Asia are summarised. RESULTS: The author'
      s experience and the Asian scientific contributions to the global research in the
      following areas are reviewed: the safety of vasectomy and the development of new
      methods of vas occlusion; gossypol and its failure to become a safe, reversible
      male antifertility drug; Tripterygium and whether its pure extracts will pass
      through the appropriate toxicology and phased clinical studies to become
      acceptable contraceptive drugs; hormonal methods of contraception for men.
      CONCLUSION: The WHO policy of research capacity building through training and
      institution strengthening, together with the collaboration of Asian andrologists,
      has created strong National institutions now able to direct their own programmes
      of research in clinical and scientific andrology.

PMID- 11225909
TI  - A novel E153X point mutation in the androgen receptor gene in a patient with
      complete androgen insensitivity syndrome.
AB  - AIM: To study a 46, XY newborn patient with a phenotype suggestive of an androgen
      insensitivity syndrome to confirm an anomaly in the AR gene. METHODS: Genomic DNA
      from leukocytes was isolated in order to analyze SRY gene by PCR and sequencing
      of the eight exons of AR gene. Isolation of human Leydig cell mesenchymal
      precursors from the testis was performed in order to study testosterone
      production and response to hCG stimulation in culture. RESULTS: Surgical
      exploration disclosed two testes, no Wolffian structures and important Mullerian
      derivatives. The SRY gene was present in peripheral blood leukocytes. Sequencing
      of the AR gene evidenced a previously unreported G to T transversion in exon 1
      that changed the normal glutamine 153 codon to a stop codon. Interstitial cell
      cultures produced sizable amounts of testosterone and were responsive to hCG
      stimulation. CONCLUSION: This E153X nonsense point mutation has not been
      described previously in cases of AIS, and could lead to the synthesis of a short
      truncated (153 vs 919 residues) non functional AR probably responsible for the
      phenotype of complete androgen insensitivity syndrome (CAIS).

PMID- 11225910
TI  - Ultrastructure of mouse teratozoospermia induced by parathion.

PMID- 11225911
TI  - CANAS 99--Colloquium on Analytical Atomic Spectrometry, Konstanz, Germany, March
      14 to 19, 1999.

PMID- 11225912
TI  - Tungsten atomizer--theory of atomization mechanism of some volatile analytes.
AB  - Several types of chemical reactions may participate in the evolution of free
      atoms in a tungsten furnace. Reactions may take place either in the homogeneous
      or heterogeneous phase. The assumed reactions may be classified into four types
      according to the phases in which they take place. Reactions occurring in the
      gaseous phase, i.e. in the inner volume of the furnace, are kinetically more
      significant. However, for atomization of easily volatile analytes heterogeneous
      reaction between gaseous compounds and between condensed salts of analytes and
      the solid surface of the furnace become significant. With regards to the reaction
      mechanisms during drying, pyrolysis and atomization of nitrates of volatile
      analytes, three basic types of chemical reactions may be assumed. Free atoms of
      analytes arise by evaporation of the elementary form of analytes at atomization
      temperature, where the particular analyte in its elementary form is produced by
      direct reduction of analyte nitrate by tungsten or by hydrogen at higher
      temperatures. Precursory reactions of atom formation are reduction reactions
      which occur between analyte nitrates and tungsten, between analyte nitrates and
      hydrogen, as well as reactions of thermal dissociation of relevant nitrates. The
      importance of particular types of precursory reactions for formation of metallic
      analytes or their oxides is documented by dependence of Gibbs energy values of
      particular reactions on the temperature.

PMID- 11225913
TI  - Vanadium in marine mussels and algae.
AB  - A method is presented which is sensitive enough for the determination of vanadium
      (V) in marine organisms such as mussels and algae. It was sufficiently checked by
      a reference material and it was applied to V determination in blue mussels and
      brown algae from the German Bight.

PMID- 11225914
TI  - Determination of analytical limits in solid sampling ETAAS: a new approach
      towards the characterization of analytical quality in rapid methods.
AB  - In the present study the lower analytical limits of solid sampling electrothermal
      atomization atomic absorption spectrometry (SS-ETAAS) were characterized by means
      of blank measurements and--for the first time--by means of the calibration curve
      method, where a calibration near the range of these limits (limit of decision,
      detection and quantification) was performed. The limit of decision as derived
      from blank measurements was calculated according to the 3sigma-criterion to be
      0.003 and 0.019 ng for Cd and Pb, respectively. For Pb and Cd a roughly three
      fold increase of these limits was observed when the calibration method according
      to DIN 32 645 was applied. When solid reference material was used, only a slight
      increase could be observed. The analytical limits were 2 to 20 times lower than
      reported for sample decomposition methods. The blank measurement and conventional
      calibration curve method, however, do not account for factors relating to solid
      sampling such as sample mass and matrix. Therefore, the calibration curve model
      was applied to data derived from comparisons between direct solid sampling ETAAS
      and a compound reference method (ETAAS following sample homogenization and
      digestion). The observed analytical limits were not found to be substantially
      increased if enough samples with low element contents were available for
      calibration. Coupling of the calibration curve model with the comparison of
      methods included real test samples and thus the relevant maximum sample mass and
      analyte content in the range of the lower analytical limits. As validation
      procedures frequently include comparisons of methods, the present approach might
      prove to be of some general interest for the characterization of analytical
      quality in rapid methods.

PMID- 11225915
TI  - Determination of soluble and insoluble nickel compounds in airborne particulate
      matter by graphite furnace atomic absorption spectrometry and inductively coupled
      plasma mass spectrometry.
AB  - An extraction procedure for the determination of soluble and insoluble nickel and
      its compounds in ambient air dust was investigated employing a special device for
      the generation of test aerosols and using water-soluble NiCl2, partly water
      soluble NiCO3 and water-insoluble NiO as model compounds. Additionally, results
      of the separation and determination of different nickel species down to some
      ng/m3 in ambient aerosols are discussed. The extraction was carried out with a
      solution containing 0.01 mol/L EDTA in order to determine partly water-soluble
      compounds such as NiCO3 and water-soluble, non-toxic nickel compounds in one
      step. Airborne dust was sampled on filters at locations close to two
      metallurgical plants in Northrhine-Westphalia (Germany), and first results on the
      nickel concentration (mean (median) values over a period of 4 months: 8.6+/-6.5
      ng/m3 (6.7 ng/m3) and 27.7+/-36 ng/m3 (10.8 ng/m3), respectively) in the
      collected dust are presented. For EDTA-soluble nickel compounds the maximum and
      mean fractions of total nickel were found to be 77.1% and 18.6+/-12%,
      respectively.

PMID- 11225916
TI  - Accurate and precise spectrochemical analysis of Bi-Pb-Sr-Ca-Cu-O high
      temperature superconductor materials.
AB  - For quality tests of ceramic Bi-Pb-Sr-Ca-Cu-O superconductor materials
      (precursors and final products) accurate stoichiometric determinations of the
      metallic major components are necessary. Three methods were developed during the
      last decade in our group. Their properties and the results obtained are compared.
      The first classical analytical procedure requires to much manpower. The second
      combined chemical-spectrometric procedure is a routine method today, but also
      unsuitable for rapid tests. A new fully spectrometric procedure was recently
      developed using a simultaneously working Echelle spectrometer with CID detector,
      autosampler and a special self-made data evaluation software. The basis of this
      method are multiline measurements of each analyte element, a new method of
      spectral line selection for main component precision determinations, multi
      component calibrations, and frequent external standardizations. For this method
      the sum of the confidence intervals of all element determinations was less than
      1%, and no systematic error was detected.

PMID- 11225917
TI  - Analytical application of 2f-wavelength modulation for isotope selective diode
      laser graphite furnace atomic absorption spectroscopy.
AB  - Experiences in the analytical application of the 2f-wavelength modulation
      technique for isotope selective atomic absorption spectroscopy in a graphite
      furnace are reported. Experimental as well as calculated results are presented,
      mainly for the natural lithium isotopes. Sensitivity, linearity, and (isotope)
      selectivity are studied by intensity modulation and wavelength modulation. High
      selectivities can be attained, however, on the cost of detection power. It is
      shown that the method enables the measurement of lithium isotope ratios larger
      than 2000 by absorption in a low-pressure graphite tube atomizer.

PMID- 11225918
TI  - Laser atomic absorption spectrometry of excited Hg in a discharge applying sum
      frequency mixing of two diode lasers (preliminary results).
AB  - Wavelength modulation diode laser atomic absorption spectrometry is applied to
      the detection of atomic mercury. Transitions from metastable energy levels highly
      populated in a radio-frequency discharge are induced with laser diodes by use of
      nonlinear techniques. The wavelength of one strong transition at 365.119 nm with
      a high oscillator strength is obtained by sum frequency generation of two diode
      lasers. The cold vapor technique is used to transfer ionic into atomic mercury.
      The mercury in the vapor phase is transported by an argon stream into the
      discharge tube. From the time-dependent absorption signals detection limits of
      100 ng/L are achieved at this state of research.

PMID- 11225919
TI  - Inductively coupled plasma mass spectrometry: a versatile tool for a variety of
      different tasks.
AB  - In a laboratory that is working in many different fields, a systematic approach
      is needed to decide efficiently how a given analytical task should be handled.
      Four typical examples are presented to show how ICP-MS may be used to solve
      client's problems. The examples are: the identification of lead projectiles, the
      determination of total and leachable fractions of impurities in a polymer (PVDF),
      used for manufacturing components of ultrapure water distribution systems, the
      authentication of antique silver alloys, and the determination of rare earth
      elements in geological materials. These examples demonstrate not only typical
      challenges for the instruments and the analysts handling them, but also ways to
      reach a satisfactory solution within a reasonable amount of time.

PMID- 11225920
TI  - Use of ultrasonic nebulizer with desolvator membrane for the determination of
      titanium and zirconium in human serum by means of inductively coupled plasma-
      mass spectroscopy.
AB  - A technique for the determination of titanium and zirconium in human blood serum,
      after pressurized digestion utilizing ICP-MS coupled to an ultrasonic nebulizer
      (USN) and desolvating membrane is described. As no CRM for titanium is available,
      zirconium has been determined in order to demonstrate the accuracy of the
      technique, as the limits in blood are well known. Bone cement consists basically
      of a polymer, namely polymethylmethacrylate (PMMA). For better X-ray contrast
      some manufacturers use incorporated ZrO2 with a volume fraction of 10 to 15%.
      Thus, the zirconium present in the PMMA matrix can be used as an indicator for
      the PMMA particulate debris.

PMID- 11225921
TI  - Application of laser ablation inductively coupled mass spectrometry (LA-ICP-MS)
      for the determination of major, minor, and trace elements in bark samples.
AB  - The large surface area of barks from many tree species enables the effective
      accumulation of pollutants. Therefore, the analysis of bark material will provide
      useful information about the degree of pollution of a certain region. The
      determination of main, minor, and trace elements (Al, Ca, Cd, Ce, Cr, Cu, Fe, Mn,
      P, Pb, S, Ti and Zn) in bark was performed with an Nd:YAG laser coupled to an ICP
      MS system. Bark standards for the calibration by laser ablation ICP-MS were
      prepared from different bark layers which differ for some relevant elements in
      concentrations. Four digestion procedures for the decomposition of the standard
      pellets, the numbers of laser shots per sample and of samples per region
      necessary have been investigated. Representative results were obtained for 5 or
      more samples taken from different individuals of one species of a sampling area
      and the averaged element concentrations of 10 separately placed laser shots for
      each sample. Laser ablation ICP-MS was applied for the characterization of real
      bark samples from different regions with high and low pollution burden. It was
      shown that the method is well suited to characterize different degrees of
      environmental impact. Anthropogenic sources were responsible for the higher
      concentrations of most of the elements under investigation.

PMID- 11225922
TI  - Lead isotope measurements on aerosol samples with ICP-MS.
AB  - Size fractionated aerosols were collected with low pressure Berner impactors on a
      radio/TV tower 110 m above ground on a hill 10 km east of Bern at a total
      elevation of 1060 m asl. Two different wind sectors were chosen with the goal of
      assessing any differences in lead concentration and the 3 radiogenic lead
      isotopes (206,207,208) for east and west wind, respectively. A leaching technique
      was used to extract the lead quantitatively from the surface of the impaction
      foils. This method has been proven to be better suited for airborne particles
      than complete microwave digestion because it is less time consuming and
      contamination risk is smaller. Blank considerations played a major role in
      choosing all the chemicals, tubes, beakers and selecting the analytical method.
      Lead concentrations were determined with GF-AAS and lead isotopes with two
      different ICP-MS systems, one being a multicollector system. Precision of the
      simultaneous multicollector system was found to be at least a factor of 3 better
      than that of the sequentially operating ICP-MS. The small variations in isotope
      ratios from the two wind sectors can be distinctly seen with this enhanced
      precision. The observed relative difference in isotope ratios between east- and
      westwind was approximately 0.6% for 207Pb/206Pb and approximately 0.5% for
      208Pb/206Pb.

PMID- 11225923
TI  - Fast determination of trace elements on aerosol-loaded filters by X-ray
      fluorescence analysis considering the inhomogeneous elemental distribution.
AB  - X-ray fluorescence (XRF) analysis was successfully applied for the determination
      of Ca, Cu, Fe, Mn, Ni, Pb, V and Zn on aerosol filters with a diameter of 150 mm.
      Ambient aerosol was collected on quartz-fibre filters by Digitel high-volume
      samplers. For XRF analysis three small filter pieces with a diameter of 32 mm
      were cut out of each filter, considering the radial dependence of elemental
      distribution on the filter. Elemental concentration decreases by 8-10% from the
      centre to the outer circle for coarse mode elements. Distribution of fine mode
      elements display only small radial dependence (2-4%). Results of quantitative
      analysis by XRF were compared with atomic spectrometric methods (GF-AAS, ICP
      OES). The good agreement between the methods confirmed the application of XRF
      spectrometry for routine analysis of filter samples loaded with ambient aerosol.

PMID- 11225924
TI  - Online monitoring of aerosols with an energy-dispersive X-ray spectrometer.
AB  - A continuously working sampling and analyzing device was developed and tested. It
      is suitable for monitoring of metals bound to particulate matter in emissions of
      stack gases. The samples were precipitated on a pure quartz fiber filter tape and
      analyzed shortly afterwards non-destructively by an energy dispersive X-ray
      spectrometer (EDXRS). By using this method a wide range of elements with atomic
      numbers from 19 (K) to 82 (Pb) can be analyzed. New experiments have shown that
      the novel combined particle sampling and analysis system (X-DUST) could also
      successfully be used for the monitoring of toxic elements in ambient air.

PMID- 11225925
TI  - Determination of cadmium by flow injection-chemical vapor generation-atomic
      absorption spectrometry.
AB  - A method was developed for the generation of a "cold vapor" of cadmium by means
      of flow injection-chemical vapor generation from aqueous samples, the
      determination being conducted with an atomic absorption spectrometer (Pyrex glass
      T-cell). Several gas-liquid separator designs, atomizer designs, and the effect
      of several reagents previously reported as sensitivity enhancers (including
      cobalt, nickel, thiourea and didodecyl-dimethylammonium bromide) were
      investigated. The limit of detection, calculated as the concentration giving a
      signal equal to three times the standard deviation of the blank, was 16 ng L(-1),
      and the relative standard deviation was 1.4% for a concentration of 2 microg L(
      1) and 3.8% for 0.1 microg L(-1). The addition of nickel and thiourea to the
      samples provided improved tolerance to the interference of coexisting ions. Two
      NIST certified reference materials, Montana Soil and Apple Leaves (respectively
      containing 41.7+/-0.25 mg kg(-1) Cd and 0.013+/-0.002 mg kg(-1) Cd) were
      accurately analyzed. The interference of lead was overcome by coprecipitation
      with barium sulfate, and the experimental values obtained were 41+/-1 mg kg(-1)
      Cd and 0.013+/-0.002 mg kg(-1) Cd, respectively.

PMID- 11225926
TI  - Monitoring of total Hg in the river Elbe: FIA-device for on-line digestion.
AB  - The development of an apparatus for the on-line sampling, digestion and
      quantification of total mercury in surface water is described. Detection and
      quantification is done by flow injection cold vapor atomic absorption
      spectroscopy (FI-CVAAS). Three digestion methods were tested, chemical, microwave
      and UV. The influence of the digestion parameters (digestion method, digestion
      time, microwave power, concentration of oxidation solution) on the recovery of
      mercury in water of the river Elbe have been investigated. Mercury can be
      determined almost quantitatively (recovery rate > 85%) with some digestion
      procedures described. The best results were reached by UV digestion. The
      technique is fast, simple to handle and robust. Each complete analysis only take
      four minutes. The working range is 10 to 1000 ng/L. The measuring arrangement has
      been applied successfully in a governmental monitoring station at
      Schnackenburg/Elbe, Germany.

PMID- 11225927
TI  - On-line determination of mercury in river water at the German monitoring station
      Schnackenburg/Elbe.
AB  - A monitor is described which provides the on-line determination of mercury in
      river water at concentrations from 20 to 1000 ng/L. The measurement includes an
      on-line digestion with Br-/BrO3- and UV-radiation. Each determination is
      controlled by an on-line addition of 50 and 100 ng/L mercury carried out by pre
      dilution of a 500 and 1000 ng/L stock solution using sequential injection
      analysis (SIA). One cycle of analysis takes 20 min and results in nine signals. A
      five days stand-alone operation has been performed successfully. Details are also
      published at web page: "http/www.rzbd.fh-hamburg.de/-prmercol".

PMID- 11225928
TI  - Determination of arsenic species in water, soils and plants.
AB  - Ion chromatographic separation coupled with ICP-MS was used to determine arsenic
      species in plant and soil extracts. A scheme for growth, harvesting, sample pre
      treatment and analysis was developed for the arsenic species to enable
      determination. Preliminary results obtained with ten herb plants grown on arsenic
      contaminated soil compared to non-contaminated soil show a heterogeneous pattern
      of accumulation rate, metabolization and detoxification mechanisms in monocots
      and dicots. Arsenite appears to be the major component in plants with good
      growth. Organic arsenic species were even detected at very low concentrations (<
      150 microg kg(-1) (dry mass)).

PMID- 11225929
TI  - Solar blind photocell--a simple element specific detector in Hg, As and Se
      speciation.
AB  - An element-specific detection method, based on atomic absorption spectrometry
      (AAS) using solar blind photocells instead of a dispersion system, is described
      for the determination of Hg-, As-, and Se-species. Spectrometric investigations
      of AAS background lamps for As and Se measured with a CsI-cathode photocell shows
      its quality as narrow band detector. Species determination can be carried out
      subsequently to prior separation by HPLC or GC. The LODs for alkylated Hg species
      were below 1 ng/L, and for methylated As species below 1 microg/L. The relative
      standard deviation was < 10%. With the components described the production of
      cheap and automated dedicated speciation spectrometers is possible.

PMID- 11225930
TI  - Speciation of copper, lead and cadmium in aquatic systems by circulating dialysis
      combined with flame AAS.
AB  - The assessment of free Cu(II), Pb(II) and Cd(II) ions in the presence of
      complexed species was realised by a circulating dialysis with Cuprophan planar
      membranes and subsequent quantification by flame atomic absorption spectrometry.
      The effect of the flow rate, the time of equilibration, pH and the presence of
      various complexing agents in the donor solutions were studied. The determination
      of free Cu(II), Pb(II) and Cd(II) ions in the presence of soil humic substances
      resulted from the above studies.

PMID- 11225931
TI  - Understanding triadic and family group interactions during infancy and
      toddlerhood.
AB  - This paper outlines recent conceptual and methodological developments in the
      assessment of triadic and family group process during infancy and toddlerhood.
      Foundations of the emerging family group process are identified, and conditions
      specific to the assessment of the family during the early phases of family
      formation are summarized. Both microanalytic and global approaches to evaluating
      mother-father-child interactions are discussed. We highlight both similarities
      and differences in the strategies and methods employed by several different
      investigators who have been studying the group dynamics of families with infant
      and toddler children, and underscore several important family patterns and
      emerging themes that appear to be cutting across these different methods and
      measurement strategies. Preliminary evidence for the validity and clinical
      significance of family-level assessments is summarized, and directions currently
      being pursued by researchers engaged in studies of the family triad are outlined.
      We close by identifying several conceptual and clinical issues that remain to be
      addressed by subsequent work.

PMID- 11225932
TI  - Corporal punishment by American parents: national data on prevalence, chronicity,
      severity, and duration, in relation to child and family characteristics.
AB  - We present data on corporal punishment (CP) by a nationally representative sample
      of 991 American parents interviewed in 1995. Six types of CP were examined: slaps
      on the hand or leg, spanking on the buttocks, pinching, shaking, hitting on the
      buttocks with a belt or paddle, and slapping in the face. The overall prevalence
      rate (the percentage of parents using any of these types of CP during the
      previous year) was 35% for infants and reached a peak of 94% at ages 3 and 4.
      Despite rapid decline after age 5, just over half of American parents hit
      children at age 12, a third at age 14, and 13% at age 17. Analysis of chronicity
      found that parents who hit teenage children did so an average of about six times
      during the year. Severity, as measured by hitting the child with a belt or
      paddle, was greatest for children age 5-12 (28% of such children). CP was more
      prevalent among African American and low socioeconomic status parents, in the
      South, for boys, and by mothers. The pervasiveness of CP reported in this
      article, and the harmful side effects of CP shown by recent longitudinal
      research, indicates a need for psychology and sociology textbooks to reverse the
      current tendency to almost ignore CP and instead treat it as a major aspect of
      the socialization experience of American children; and for developmental
      psychologists to be cognizant of the likelihood that parents are using CP far
      more often than even advocates of CP recommend, and to inform parents about the
      risks involved.

PMID- 11225933
TI  - Triple P-Positive Parenting Program: towards an empirically validated multilevel
      parenting and family support strategy for the prevention of behavior and
      emotional problems in children.
AB  - This paper outlines the theoretical and empirical foundations of a unique
      multilevel parenting and family support strategy designed to reduce the
      prevalence of behavioral and emotional problems in preadolescent children. The
      program known as Triple P-Positive Parenting Program is a multilevel system of
      family intervention, which provides five levels of intervention of increasing
      strength. These interventions include a universal population-level media
      information campaign targeting all parents, two levels of brief primary care
      consultations targeting mild behavior problems, and two more intensive parent
      training and family intervention programs for children at risk for more severe
      behavioral problems. The program aims to determine the minimally sufficient
      intervention a parent requires in order to deflect a child away from a trajectory
      towards more serious problems. The self-regulation of parental skill is a central
      construct in the program. The program uses flexible delivery modalities
      (including individual face-to-face, group, telephone assisted, and self-directed
      programs) to tailor the strength of the intervention to the requirements of
      individual families. Its multidisciplinary, preventive and community-wide focus
      gives the program wide reach, permitting the targeting of destigmatized access
      points through primary care services for families who are reluctant to
      participate in parenting skills programs. The available empirical evidence
      supporting the efficacy of the program is discussed and its implications for
      research on dissemination are discussed.

PMID- 11225934
TI  - The assessment of normal fear in children and adolescents.
AB  - Published research into normal fear now spans more than one century. During this
      time, a large number of papers have been published in the area. The resulting
      literature has led to a detailed understanding of normal fear experiences and, in
      particular, the ways in which they change with maturation. Of central importance,
      when evaluating the documented outcomes of this work, is the soundness of the
      methods and tools used in assessment. It is not surprising given the large number
      of researchers that have been involved in this area, that the assessment methods
      used have varied substantially. These have ranged from the methodologically
      problematic technique of obtaining retrospective adult reports to the
      administration of psychometrically validated fear survey schedules. An extensive
      review of this literature reveals that, for the last two decades, the fear survey
      schedule has been the most widely used technique for the fear assessment. The
      preference that has and is being demonstrated for the fear survey schedule as an
      assessment tool is most likely due to its many advantages including ease of use,
      objectivity in scoring, and provision of a substantial amount of information in a
      short period. However, despite its advantages, researchers and clinicians need to
      be cognizant of its potential limitations and, depending on the questions being
      asked, may need to consider using it in combination with alternative assessment
      strategies.

PMID- 11225936
TI  - Intravenous MgSO4 alone and in combination with glucose, insulin and potassium
      (GIK) prolong the atrial cycle length in chronic atrial fibrillation.
AB  - AIMS: To investigate the effects of parenteral administration of MgSO4, and
      glucose, insulin, and potassium (GIK), on the dominant atrial cycle length during
      chronic atrial fibrillation (CAF). METHODS AND RESULTS: The length of the
      dominant atrial cycle (DACL) in the power-frequency spectrum of the QRST
      suppressed lead V1 ECG was identified before and after intravenous administration
      of MgSO4 alone and after 5 and 10 h of MgSO4 and GIK infusion, in 13 patients
      with CAF. The changes in DACL were compared with changes in heart rate (HR),
      blood pressure and blood parameters. MgSO4 alone increased the DACL from 146(13)
      (mean(SD)) (control) to 153(14) ms (P < 0.01) and decreased the HR from 102(22)
      to 95(18) beats x min(-1) (P < 0.05). After 5 h of MgSO4 and GIK infusion the
      DACL was increased compared with control, from 146(13) to 152(11) ms (P < 0.01),
      but unchanged compared with that after the bolus infusion of MgSO4. HR was
      decreased compared with control (102(22)) and the bolus infusion of MgSO4
      (95(18)) to 87(15) beats x min(-1) after 5 h of intervention. The DACL was
      further increased after 10 h of MgSO4 and GIK infusion compared with both control
      (from 146(13) to 157(11) ms), (P < 0.01) and the 5h infusion (152(11) to 157(11)
      ms), (P < 0.05). No further changes were seen in HR after 10 h (87(17)) of
      intervention. There were indications of an inverse relationship between total
      changes in HR (deltaHR) and DACL (deltaDACL) during the interventions (P < 0.05).
      CONCLUSION: Bolus infusion of MgSO4 prolongs the DACL and decreases HR in CAF. A
      further prolongation of DACL was seen after 10 h of MgSO4 and GIK infusion
      compared with control and with 5 h of intervention. Changes in DACL and HR during
      the entire intervention period showed an inverse relationship. The antiarrhythmic
      properties of MgSO4 and the GIK solution in CAF clearly require further
      attention.

PMID- 11225937
TI  - Stroke prevention practices in patients with atrial fibrillation and pacemaker
      therapy: evidence for under-use of anticoagulation.
AB  - This study presents a survey of pacemaker patients followed in a pacemaker
      clinic. Three hundred and twenty-six patients of mean age 77.7 +/- 9.6 years, 52%
      female, 75% VVI, 25% dual chamber were analysed. One hundred and forty (43%) were
      in atrial fibrillation and were older, 80.5 +/- 7.1 years, compared with 75.5 +/-
      11.4 years (P = 0.014) for those in sinus rhythm. Temporary pacemaker
      reprogramming was necessary in 86% in order to determine the abnormal rhythm.
      Thirty-nine (28%) of those in atrial fibrillation were anticoagulated; 37% were
      on aspirin; only 10.8% of those in atrial fibrillation who were not
      anticoagulated had contraindications to this therapy. Prevalence of atrial
      fibrillation increased with age, whereas that of anticoagulation decreased with
      age. In conclusion, the majority of pacemaker patients with atrial fibrillation,
      for whom anticoagulation is indicated, fails to receive it: those caring for
      these patients are urged to ensure its much wider use.

PMID- 11225938
TI  - Early cardioversion of atrial fibrillation and atrial flutter guided by
      transoesophageal echocardiography: a single centre 8.5-year experience.
AB  - AIMS: To analyse the safety and impact on maintenance of sinus rhythm of
      transoesophageal echocardiographically guided early cardioversion associated with
      short-term anticoagulation in a large series of patients with atrial fibrillation
      and atrial flutter. METHODS AND RESULTS: Patients who were candidates for
      cardioversion were eligible for inclusion if they had atrial fibrillation or
      atrial flutter lasting longer than 2 days or of unknown duration. Patients
      received short-term anticoagulation with warfarin or heparin and underwent
      transthoracic echocardiography followed by transoesophageal echocardiography.
      Early cardioversion was performed if no thrombus was seen on the transoesophageal
      study. Warfarin was maintained for 1 month after cardioversion. In patients with
      atrial thrombi, cardioversion was deferred and prolonged anticoagulation was
      prescribed. The study population included 183 patients. One hundred and sixty
      nine patients without atrial thrombi underwent early cardioversion. Fourteen
      patients with atrial thrombi (7.6%) underwent a second transoesophageal
      echocardiogram after a median of 4 weeks of oral warfarin, and cardioversion was
      performed if clot regression was documented. No patient in our study population
      had a clinical thromboembolic event at 1 month follow-up (95% C.I. 0-0.016). The
      immediate success rate of cardioversion was better among patients with atrial
      fibrillation < 4 weeks duration compared with patients with atrial fibrillation
      of longer or of unknown duration: 96.6% vs 85%, respectively (P = 0.014). At 1
      month follow-up, the percentage of arrhythmia relapses in patients with initially
      successful cardioversion was similar in the two groups (29% vs 26%, P = ns); thus
      the initial better outcome in patients with recent-onset arrhythmia was not lost.
      CONCLUSION: Transoesophageal echocardiography-guided early cardioversion in
      concert with short-term anticoagulation is safe. This approach permits
      abbreviation of the overall duration of atrial fibrillation and has a better
      impact on the maintenance of sinus rhythm for patients in whom the duration of
      atrial fibrillation is < 4 weeks.

PMID- 11225939
TI  - Does the mechanism of action of biatrial pacing for atrial fibrillation involve
      changes in cardiac haemodynamics? Assessment by Doppler echocardiography and
      natriuretic peptide measurements.
AB  - AIMS: The antifibrillatory mechanism of biatrial (BI) pacing has not been fully
      elucidated. We investigated the role of a haemodynamic mechanism in eight
      patients implanted with a BI pacemaker (Chorus RM) by comparing changes in mitral
      Doppler flow and atrial and B-type natriuretic peptide levels (ANP, BNP) with BI
      pacing compared with sinus rhythm and right atrial (RA) pacing. METHODS AND
      RESULTS: Measurements were taken after 60 min in the supine position in each of
      two pairs of randomized pacing modes: (a) AAI40 beats x min(-1), (allows sinus
      rhythm mean rate 56 beats x min(-1), SR) vs AAI 40 beats x min(-1) with
      synchronized left atrial pacing (SRSync); (b) overdrive AAI RA pacing (89 beats x
      min(-1) (n = 6) or 70 beats x min(-1) (n = 2)) vs overdrive AAI BI pacing. Within
      each pair there was significant earlier activation of the left atrial Doppler
      signal in relation to the surface ECG P wave with BI pacing (SR 163 +/- 10 ms vs
      SRSync 144 +/- 21 ms (P = 0.02), and RA 232 +/- 14 ms vs BI 196 +/- 16 ms (P =
      0.001)), and significant shortening of the P-R interval (SR 163 +/- 29 ms vs
      SRSync 148 +/- 20 (P = 0.007) and RA 261 +/- 27 ms vs BI 232 +/- 23 (P = 0.001)).
      The net observed effect was of no change in the atrioventricular timing sequence
      (delay of peak E or A to QRS/ mitral valve closure) and no change in other
      Doppler echo parameters. Levels of the cardiac peptides ANP and BNP were raised
      compared with healthy controls, but did not significantly change during the
      study. CONCLUSION: Acute BI pacing shortens the P-R interval and causes earlier
      left atrial contraction in relation to the surface electrocardiogram P wave. It
      does not alter the atrioventricular timing cycle, any other Doppler measurements
      or change cardiac peptide levels. This suggests that BI pacing does not cause
      haemodynamic changes that could account for any antifibrillatory properties.

PMID- 11225940
TI  - Identification of post-myocardial infarction patients prone to ventricular
      tachycardia using time-frequency analysis of QRS and ST segments.
AB  - BACKGROUND: Late potentials (LPs) in the terminal portion of the QRS complex are
      commonly sought to identify post-myocardial infarction patients prone to
      ventricular tachyarrthythmias (VT) or sudden death. More recent time frequency
      signal processing tools have been shown to provide new parameters for the
      quantification of LPs and abnormal activities buried within the QRS complex.
      METHODS AND RESULTS: The study population comprised 23 myocardial infarction
      patients with documented sustained VT (MI+VT), 40 myocardial infarction patients
      without VT (MI - VT) and 31 normal subjects. The reproducibility of the method
      was tested in an additional set of 66 patients. The signal-averaged high
      resolution electrocardiograms (HRECGs) were quantified by deconstructing the
      unfiltered X, Y and Z leads using a 511-orthogonal wavelet network. Using
      receiver operating characteristics (ROC) curves and discriminant analysis applied
      to the wavelet coefficients, we extracted the most significant wavelets to
      classify the post MI patients. These wavelets detected time-frequency alterations
      both in the ST segment and within the QRS complex, characterizing patients prone
      to VTs. The same statistical methods were applied to the conventional time-domain
      measurements. The combined application in our population of the orthogonal
      wavelet deconstruction method and discriminant analysis had 91% sensitivity and
      95% specificity, an improvement of 22% and 25%, respectively, compared with the
      conventional time domain method. Reproducibility was 82%. CONCLUSIONS: In post
      myocardial infarction patients, orthogonal wavelet transforms can detect
      alterations in high-frequency components within the QRS and ST segment. Our
      findings support the view that wavelet-related parameters are more relevant than
      those of the time domain method in predicting subsequent malignant
      tachyarrhythmias.

PMID- 11225935
TI  - Effective treatment for mental disorders in children and adolescents.
AB  - As pressure increases for the demonstration of effective treatment for children
      with mental disorders, it is essential that the field has an understanding of the
      evidence base. To address this aim, the authors searched the published literature
      for effective interventions for children and adolescents and organized this
      review as follows: (1) prevention; (2) traditional forms of treatment, namely
      outpatient therapy, partial hospitalization, inpatient treatment, and
      psychopharmacology; (3) intensive comprehensive community-based interventions
      including case management, home-based treatment, therapeutic foster care, and
      therapeutic group homes; (4) crisis and support services; and (5) treatment for
      two prevalent disorders, major depressive disorder and attention-deficit
      hyperactivity disorder. Strong evidence was found for the treatment of attention
      deficit hyperactivity disorder, depression, anxiety, and disruptive behavior
      disorders. Guidance from the field relevant to moving the evidence-based
      interventions into real-world clinical practice and further strengthening the
      research base will also need to address change in policy and clinical training.

PMID- 11225941
TI  - Fractally coated defibrillation electrodes: is an improvement in defibrillation
      threshold possible?
AB  - AIMS: In patients with implantable cardioverter-defibrillators (ICD), the goals
      of lowering the defibrillation threshold (DFT) can be achieved by means of higher
      defibrillation safety margins, more rapid charging of capacitors, improved
      battery longevity, implying smaller devices. Whether an increase in the
      electrically active surface of ICD leads by fractal coating results in decreased
      DFTs is unknown. METHODS AND RESULTS: In this prospective randomized cross-over
      study the defibrillation efficacy of a novel right ventricular endocardial
      defibrillation electrode fractally coated with iridium was compared with an
      uncoated but otherwise identical electrode in 30 patients undergoing ICD
      implantation. In each patient, DFT testing was performed twice according to a
      binary search protocol introducing the two different electrodes in a random
      order. The mean DFT was 8.4 +/- 4.1 J with the fractally coated lead and 9.6 +/-
      3.6 J using the uncoated lead. The improvement of 1.2 J was statistically not
      significant (P = 0.11). No differences were observed between the patients with an
      improved DFT (n =12) and those with an unchanged or worsened DFT (n = 18)
      concerning age, underlying cardiac disease, NYHA class, or left ventricular
      ejection fraction, respectively. CONCLUSION: Increasing the electrical surface of
      defibrillation leads by fractal coating does not lead to a substantial clinically
      relevant reduction in defibrillation thresholds. Defibrillation impedance is not
      influenced by the increased electrical surface of the defibrillation lead.

PMID- 11225942
TI  - Detection of ventricular fibrillation in implantable defibrillators with
      automatic gain control amplifiers: effects of programming sensitivity.
AB  - AIMS: In newer implantable cardioverter-defibrillators with automatic gain
      control amplifiers the maximum possible sensitivity is programmed with the aim of
      securing optimal detection of ventricular fibrillation. This study was designed
      to prove that a reduction in maximum sensitivity is safe with respect to
      appropriate sensing of ventricular fibrillation, while avoiding sensing of
      extracardiac signals. METHODS AND RESULTS: Forty-two consecutive patients,
      undergoing defibrillator implantation/replacement with programmable maximum auto
      gain sensing sensitivity (Ventak Mini III, Ventak AV , Guidant, St. Paul, MN,
      U.S.A.), were prospectively investigated. Thirty-four patients were implanted
      with a dual-coil lead system, providing integrated bipolar sensing (Endotak,
      Guidant, St. Paul, MN, U.S.A.), eight patients received a single-coil lead system
      with true bipolar sensing (Sprint, Medtronic, Minneapolis, MN, U.S.A.). During
      device implantation and pre-discharge testing, arrhythmia detection times of
      induced ventricular fibrillation were compared at programmed maximum (0.18 mV)
      and minimum (0.43 mV) sensitivity in a randomized manner. Seventy-six induced
      episodes of ventricular fibrillation were analysed. The mean arrhythmia detection
      times did not differ between the programmed sensing levels (maximum sensitivity:
      1612 +/- 307 ms, vs minimal sensitivity: 1,602 +/- 330 ms; P = ns). The results
      were not affected by the type of implanted lead system (integrated bipolar versus
      true bipolar sensing). CONCLUSION: In the implantable defibrillator devices,
      reduction in maximum sensitivity did not impair the detection of induced episodes
      of ventricular fibrillation.

PMID- 11225943
TI  - A jump in cycle length of orthodromic common atrial flutter during catheter
      ablation at the isthmus between the inferior vena cava and tricuspid annulus;
      evidence of dual isthmus conduction directed to dual septal exits.
AB  - INTRODUCTION: In orthodromic common atrial flutter (AFL), details of intraseptal
      propagation of the flutter (FL) wave exiting from the isthmus between the
      inferior vena cava and tricuspid annulus (IVC-TA isthmus) remain unknown. We
      hypothesized the existence of dual septal exits of the FL wave from the IVC-TA
      isthmus to both the anterior, coronary sinus ostium (CSO-TA) isthmus, and the
      posterior septal (IVC-CSO) isthmus, and that the IVC-TA isthmus might consist of
      dual muscle bundles directed to both septal isthmuses over the eustachian ridge;
      therefore, segmental ablation of the IVC-TA isthmus could change intraseptal FL
      wave propagation. METHODS AND RESULTS: To test the hypothesis, we investigated
      the influence of segmental ablation of the IVC-TA isthmus on intraseptal FL wave
      propagation. In seven of 40 (18%) consecutive patients, segmental ablation of the
      ventricular side of the IVC-TA isthmus during orthodromic common AFL led to
      sudden prolongation of the flutter cycle length (FCL) (from 266 +/- 33 ms to 291
      +/- 45 ms) associated with changes in intraseptal activation sequences. They
      consisted of prolongation of the interval between the IVC-TA isthmus and the CSO
      (from 38 +/- 13 ms to 86 +/- 25 ms), shortening of the interval between the CSO
      and His (from 31 +/- 15 ms to 9 +/- 15 ms), and atrial electrogram polarity
      change at the His-bundle recording site. Morphological change in the FL wave was
      also seen on the 12-lead ECG. CONCLUSIONS: In some patients, segmental ablation
      of the IVC-TA isthmus can lead to a jump in FCL and changes in intraseptal
      activation sequences of FL waves due to anterior-to-posterior shifting of the
      septal exit. This indicates that the IVC-TA isthmus may contain dual
      circumferential muscle bundles as conduction pathways directed to dual septal
      exits both anterior and posterior to the CSO.

PMID- 11225944
TI  - Role of the serotonergic system in the genesis of vasovagal syncope.
AB  - AIMS: The hypotensive reflex responsible for vasovagal syncope appears related to
      a reduction in sympathetic neural outflow. Several animal studies suggest that
      serotonin may play a role in the genesis of this reflex, through inhibition of
      sympathetic activity. However, the role of the serotonergic system is unknown in
      humans. The purpose of the study was to investigate the role of the serotonergic
      system in the genesis of vasovagal syncope by means of the level of platelet and
      plasma serotonin, as well as plasma catecholamines, during tilt-induced syncope.
      METHODS AND RESULTS: Fifteen patients (age 34 +/- 16 years) with vasovagal
      syncope underwent a head-up tilt test (HUT, 60 degrees , 45 min). If syncope did
      not develop, 300 microg nitroglycerin was administered sublingually and patients
      continued to be tilted for a further 20 min. Blood samples were obtained in the
      supine position, and then after 3, 10, 15, 30, 45, 48 and 65 min of HUT. If
      syncope developed, blood samples were obtained at the beginning of the prodrome,
      during syncope and after the recovery of consciousness. Platelet and plasma
      serotonin and plasma catecholamines were measured using high-pressure liquid
      chromatography with electrochemical detection. Ten patients developed syncope
      during the unmedicated HUT and four after nitroglycerin. In these patients plasma
      adrenaline significantly increased from the last programmed sample before the
      prodrome to its beginning and showed a further increase during loss of
      consciousness, whereas plasma noradrenaline did not increase, as an expression of
      inhibition of sympathetic neural outflow. In the patients experiencing syncope,
      both platelet and plasma serotonin showed no significant change after tilt-up, at
      the beginning of prodrome, during syncope and after recovery of consciousness.
      CONCLUSION: These results do not suggest that the serotonergic system plays a
      role in the pathophysiology of vasovagal syncope.

PMID- 11225945
TI  - Autonomic effects of radiofrequency catheter ablation.
AB  - Radiofrequency (RF) catheter ablation has become the treatment of choice for a
      variety of supraventricular tachycardias. Autonomic dysfunction may occur during
      application of RF current; these abnormalities resolve quickly when current
      delivery is terminated. We present a case of sinus node arrest and AV block in a
      69-year-old woman induced by RF catheter ablation of an AV nodal slow pathway.
      The proposed mechanisms are a Bezold-Jarisch-like phenomenon or paradoxical
      activation of cardiac C fibres by direct neural sympathetic stimulation or RF
      induced myocardial injury. Based on a review of previously published reports,
      autonomic effects of RF ablation are discussed.

PMID- 11225946
TI  - Permanent pacemaker upgrade.

PMID- 11225947
TI  - Alternative right ventricular pacing sites--where are we going?

PMID- 11225948
TI  - Radiofrequency catheter ablation of atrial fibrillation initiated by spontaneous
      ectopic beats.
AB  - This paper reviews the technique of focal ablation for control of paroxysmal
      atrial fibrillation, its success rate and complications.

PMID- 11225949
TI  - Cerebral palsy and spasticity: time to empower child neurology with a
      comprehensive review. Proceedings of a consensus conference, May 2000.

PMID- 11225950
TI  - Clinical considerations in cerebral palsy and spasticity.
AB  - The ultimate goal for management of patients with cerebral palsy is to help them
      grow up to become as independent as possible, learn to make their own choices in
      life, and pursue their own dreams. Optimal mobility is crucial to achieving
      independence and is also necessary for better health and quality of life in these
      patients. This article discusses the treatment of spasticity in cerebral palsy,
      addresses tone management issues in relationship to mobility and physical
      fitness, and introduces the reader to a comprehensive approach to the management
      of patients with cerebral palsy.

PMID- 11225951
TI  - Spasticity management: an overview.
AB  - Recent developments in therapeutic interventions for children with spasticity
      have complicated managerial decision making. A simplified paradigm for the
      pathophysiology of spasticity is presented, which emphasizes the ways in which
      treatment modalities disrupt hyperexcitable segmental spinal reflex arcs. Various
      techniques for the management of spasticity are reviewed, along with factors
      relevant to proper patient selection for therapeutic intervention. Potential
      goals for spasticity management are considered as are outcome measures for
      assessing the efficacy of these technologies.

PMID- 11225952
TI  - Scientific basis of spasticity: insights from a laboratory model.
AB  - A variety of central nervous system injuries, diseases, and developmental
      deficits can lead to motor disorders that present complex mixtures of symptoms.
      Those that have a fundamental similarity characterized by the appearance of
      exaggerated velocity-dependent resistance to the lengthening of skeletal muscles
      are called spasticity. Reports based on clinical observations of motor disorders
      have and continue to provide the essential database of information regarding the
      range and distribution of unifying and discordant features of spasticity.
      Laboratory investigations employing animal models of motor disorders following
      experimental lesions of the central nervous system have reproduced some of the
      neurophysiologic changes that accompany injury of the central nervous system in
      humans. Those experimental lesions produced by spinal cord contusion/compression
      reproduce many of the histopathologic features displayed in traumatic injury of
      the human spinal cord as well. Studies using this model have revealed not only
      changes in reflex threshold and amplitude but also alterations in fundamental
      rate-modulation processes that regulate reflex excitability during repetitive
      stimulation. This report characterizes insights obtained from a laboratory
      investigation in search of fundamental mechanisms that contribute to the
      development of spasticity and provides a vantage point for understanding
      therapeutic strategies for treatment of spasticity.

PMID- 11225953
TI  - Physical management of spasticity.
AB  - Physical management of people with spasticity is a complex task requiring the
      collaborative work of a multidisciplinary team. This article reviews some of the
      most commonly used treatment techniques and theories that lay the framework for
      the physical management of spasticity. Most crucial to the management of the
      person with spasticity is the skillful application of the techniques and theories
      discussed. Given the complexity in the standardized evaluation of children with
      spasticity, it is recommended that existing outcome measures or standardized
      scales be applied wherever possible as an adjunct tool to the clinician's
      assessment and interventions. One must recognize the benefits of such scales and
      their limitations. Therefore, it is recommended that further development of
      standardized assessments be supported by funding agencies to develop both
      quantitative and qualitative measurement tools that will address the particular
      needs of the person with spasticity. Review of the literature supports the many
      interventions that are listed; however, further research is recommended by the
      consensus group.

PMID- 11225954
TI  - Pharmacotherapy of spasticity: oral medications and intrathecal baclofen.
AB  - Spasticity is a common problem in children with neurologic impairment,
      particularly in those with cerebral palsy. Clinicians commonly make use of oral
      medications to attempt to reduce spasticity and increase function. Little has
      been published in the literature concerning the use of these medications in
      children and their effects on both muscle tone and function. This article is a
      review of the sites of action, side effects, and efficacy of benzodiazepines,
      baclofen, dantrolene sodium, alpha2-adrenergic agonists, and gabapentin. A brief
      review of intrathecal baclofen is included as well.

PMID- 11225956
TI  - Spasticity: orthopedic perspective.
AB  - The orthopedic management of spasticity is based on the effects of this
      neurologic condition on the bones and tissues of the growing child. The goal of
      such intervention is to maximize function, reduce disability, and facilitate
      mobility. Goal-directed treatment plans are tailored for each patient and may
      include a combination of modalities such as physical and occupational therapy,
      casting, orthoses, and surgery. Physical and occupational therapy is emphasized
      up to 4 to 5 years of age, whereas surgery is best between 5 and 7 years of age.
      Education and psychosocial development should be emphasized beginning at age 7
      years through adulthood, with surgery reserved for more involved cases of
      contracture or bony dysplasia. In adulthood, treatment should be focused on
      integration into society and maximizing functional independence. Although there
      are many undisputed benefits of therapy, no consensus exists regarding the most
      beneficial modality, the age group that would benefit most, or whether continued
      treatment is beneficial in adulthood. Whereas the use of serial casting and tone
      reducing casts has lessened, lower extremity orthoses have gained widespread
      acceptance with improvements in design and fabrication and have been demonstrated
      to help restore normal heel-toe gait. Surgical techniques such as tendon
      lengthening, transfer, bony osteotomy, and joint fusion are time-honored
      techniques that continue to be refined with current advances in the use of
      computerized gait analysis for preoperative planning. Further research in long
      term results and outcomes measurement will be necessary to fully assess the
      impact of current treatment.

PMID- 11225955
TI  - Clinical utility of botulinum toxin in the treatment of cerebral palsy:
      comprehensive review.
AB  - The physical properties, mechanism of action, and clinical evidence supporting
      the use of botulinum toxin in the management of spasticity in cerebral palsy are
      discussed. Assessment methods, patient selection criteria, and methodology for
      preparation and administration of botulinum toxin are discussed in detail and a
      treatment algorithm based on the cumulative experience of the author is provided.
      Botulinum toxin type A is well tolerated, safe, and effective in the treatment of
      patients with spastic cerebral palsy. Appropriate patient selection is
      imperative. Treatment goals need to be well defined and tailored to the
      individual patient's needs. Growth and development is a continuous and evolving
      process, necessitating the constant reassessment of the patient and modification
      of future treatment goals. The ultimate success of management in cerebral palsy
      is dependent on the development of a comprehensive spasticity team with
      complementing skills who, together, can significantly improve the quality of life
      of these patients.

PMID- 11225957
TI  - Evolution of the neurosurgical management of spasticity.

PMID- 11225958
TI  - Cognitive and neuropsychological functioning in children with cerebral palsy.
AB  - This article reviews the extant literature on intellectual functioning in
      different subtypes of cerebral palsy. Following a definition of the
      characteristics of each of three major cerebral palsy groups, typical neurologic
      and magnetic resonance imaging findings are reported. More recent studies that
      examine the intellectual and neuropsychological functioning of children within
      these classification groups are also reviewed. This review concludes that there
      remains a significant lack of precise information about the impact of cerebral
      palsy on the intellectual, motor, and neuropsychological functioning of children
      and that neuropsychological assessment can provide the necessary tools for such
      studies.

PMID- 11225959
TI  - Consensus statement on the physical management of spasticity.

PMID- 11225960
TI  - Consensus statement on pharmacotherapy for spasticity.

PMID- 11225961
TI  - Consensus statement on the surgical management of spasticity related to cerebral
      palsy.

PMID- 11225962
TI  - Insulin-like growth factor-I for the treatment of type 1 diabetes.

PMID- 11225963
TI  - Physiology of glucose homeostasis.

PMID- 11225964
TI  - What are the barriers to medical care for patients with newly diagnosed diabetes
      mellitus?
AB  - CONTEXT: Few data are available describing factors that prevent patients with
      newly diagnosed diabetes from seeking medical care. OBJECTIVE: To identify
      socioeconomic factors that act as barriers to healthcare among such patients.
      SETTING: A community-wide diabetes screening programme. PARTICIPANTS: One hundred
      and eighteen patients with newly identified diabetes mellitus out of 1,824 total
      screenings. INTERVENTIONS: Each newly identified person with diabetes was
      instructed to contact a physician for follow-up care. DESIGN: A follow-up survey
      was obtained from 89 (75%) subjects 9 +/- 7 months after diagnosis. MAIN OUTCOME
      MEASURE: Whether or not subjects had obtained follow-up care for their diabetes.
      RESULTS: Of seven variables examined, only lack of health insurance correctly
      predicted those patients who failed to seek medical care for their diabetes by
      multivariate analysis. CONCLUSIONS: Lack of health insurance coverage is the
      primary reason that patients with newly diagnosed diabetes fail to seek medical
      care.

PMID- 11225966
TI  - Rosiglitazone prevents the onset of hyperglycaemia and proteinuria in the Zucker
      diabetic fatty rat.
AB  - AIM: To investigate the potential of rosiglitazone, a highly potent agonist at
      the nuclear peroxisome proliferator activated receptor-gamma (PPAR-gamma), to
      prevent the development of diabetes in the Zucker diabetic fatty (ZDF) rat or to
      ameliorate the condition at a later stage of the disease. METHODS: Rosiglitazone
      (10 micromol/kg body weight daily) was given via the diet to ZDF rats from aged 6
      weeks, before the onset of hyperglycaemia (Prevention group), or from aged 21
      weeks after hyperglycaemia and proteinuria were established (Intervention group).
      Untreated ZDF rats and age-matched Zucker lean rats (ZL) served as controls and
      the experiment was terminated when the animals were aged 28 weeks. RESULTS:
      Whilst the combined ZDF control and Intervention groups were already
      hyperglycaemic (14.6 +/- 1.6 vs. ZL 5.7 +/- 0.1 mmol/l, mean +/- s.e.m.; p <
      0.05), glycosuric and polydipsic at aged 11 weeks, and thereafter had a declining
      plasma insulin concentration, rosiglitazone Prevention treatment maintained
      normoglycaemia even at aged 27 weeks (3.7 +/- 0.3 mmol/l vs. ZL 3.0 +/- 0.3
      mmol/l; NS). Intervention treatment at aged 21 weeks, however, failed to
      ameliorate the diabetes. These functional data were supported by determinations
      of pancreatic insulin content (microg/mg tissue as follows: ZL, 43.1 +/- 3.9; ZDF
      control (28 weeks) + ZDF Intervention control (21 weeks), 6.0 +/- 0.8;
      Prevention, 63.6 +/- 15.8; Intervention, 6.2 +/- 0.9) and by morphological,
      immunohistochemical and electron microscopical examination of pancreata at the
      end of the study. Thus, islets from rosiglitazone Prevention rats were similar to
      ZL rats, whereas ZDF controls and Intervention rats exhibited islets depleted of
      insulin, with a disorganized architecture and an ultrastructure indicative of
      work hypertrophy. ZDF control rats and Intervention rats, though not
      rosiglitazone Prevention rats, also exhibited marked proteinuria, indicative of
      renal glomerular damage. CONCLUSIONS: Our results demonstrate that in ZDF rats,
      rosiglitazone prevents the progression from insulin resistance to overt diabetes.
      These data provide a rationale for investigating whether treatment with
      rosiglitazone of patients with early signs of perturbed glucose metabolism (e.g.
      impaired fasting glucose (IGT)) may prevent the progression to type 2 diabetes
      and its associated complications.

PMID- 11225965
TI  - Comparative efficacy study of atorvastatin vs simvastatin, pravastatin,
      lovastatin and placebo in type 2 diabetic patients with hypercholesterolaemia.
AB  - Although there is little information from primary or secondary prevention trials
      on cholesterol-lowering medication in diabetic patients, the reduction of
      elevated cholesterol is widely recommended for this group. The American Diabetes
      Association (ADA) recommends drug therapy in diabetic patients if low density
      lipoprotein (LDL)-cholesterol remains at > 130 mg/dl, or > 100 mg/dl in patients
      with macroangiopathy, after dietary intervention. When cholesterollowering
      medication is indicated, the choice of the drug must take into account the other
      lipid abnormalities that are often present and the need to maintain optimal
      glycaemic control. In the present study we compared the efficacy and safety of
      the novel HMG-CoA reductase inhibitor atorvastatin at the dose of 10 mg/day with
      simvastatin , lovastatin and pravastatin at doses of 10, 20 and 20 mg/day,
      respectively, and placebo, in type 2 diabetic patients with moderate elevation of
      LDL-cholesterol with or without elevation of triglycerides. All the quoted agents
      are enzyme inhibitors effective in lowering LDL-cholesterol in humans. The
      efficacy endpoints were the mean per cent changes in plasma LDL-cholesterol
      (primary), total cholesterol, triglycerides, and high-density lipoprotein (HDL)
      cholesterol concentrations from baseline to the end of treatment (24 weeks).
      Atorvastatin at a dose of 10 mg/day produced: (1) a significant reduction in LDL
      cholesterol (-37%) in comparison with equivalent doses of simvastatin (-26%),
      pravastatin (-23%), lovastatin (-21%), and placebo (-1%); (2) HDL-cholesterol
      increases (7.4%) comparable to or greater than those obtained with simvastatin
      (7.1%), pravastatin (3.2%), lovastatin (7.21%), and placebo (-0.5%); (3) a
      significantly greater reduction in total cholesterol (- 29%) than that obtained
      with simvastatin (-21%), pravastain (-16%), lovastatin (-18%), and placebo (1%);
      and (4) a significantly greater reduction in triglycerides than that obtained
      with all the other drugs and placebo. In all treatment groups no significant
      variation in fibrinogen concentration was observed. All reductase inhibitors
      studied had similar levels of tolerance. There were no incidents of persistent
      elevations of serum aminotransferases or myositis.

PMID- 11225967
TI  - Physiological responses during hypoglycaemia induced by regular human insulin or
      a novel human analogue, insulin glargine.
AB  - AIM: Glargine, a product of recombinant technology, has different structural and
      physicochemical properties compared with native human insulin. We determined
      whether such differences are associated with alterations in the responses to
      hypoglycaemia induced by glargine. METHODS: Nineteen adults (six healthy and 13
      with type 1 diabetes) underwent a 5-h hyperinsulinaemic (2 mU/kg/min(-1)) stepped
      hypoglycaemic clamps (hourly targets of 4.7, 4.2, 3.6, 3.1 and 2.5 mmol/l,
      respectively) on two occasions using intravenous infusion of regular human
      insulin or glargine, in random sequence. Hypoglycaemic symptoms, counter
      regulatory hormones and glucose disposal rates were assessed at intervals
      throughout the clamps. A 1-week 'wash out' period was observed between studies.
      RESULTS: The peak total symptoms scores (mean +/- s.e.m.) at nadir blood glucose
      (2.5 mmol/1) were 18.83 +/- 2.68 (healthy) and 17.46 +/- 3.62 (diabetic) during
      regular insulin, and 18.50 +/- 3.20 (healthy) and 19.08 +/- 3.83 (diabetic)
      during glargine infusion. The peak epinephrine levels during hypoglycaemia were
      767.8 +/- 140.4 pg/ml (regular insulin) and 608.8 +/- 129.9 pg/ml (glargine)
      among healthy subjects, and 332.5 +/- 54.8 pg/ml (regular insulin) and 321.8 +/-
      67.4 pg/ml (glargine) in diabetic patients. Diabetic patients had blunted
      glucagon responses during hypoglycaemia with either insulin. Both insulins also
      elicited similar rates of glucose disposal. CONCLUSIONS: We conclude that insulin
      glargine and regular human insulin elicit comparable symptomatic and counter
      regulatory hormonal responses during hypoglycaemia in healthy or diabetic
      subjects, and induce similar rates of glucose disposal. Since glargine is
      designed for subcutaneous (s.c.) use, it is possible (though unlikely) that our
      findings obtained using an intravenous protocol could differ from responses to
      hypoglycaemia induced by the s.c. route.

PMID- 11225968
TI  - Pneumococcal paraspinal pyomyositis in a diabetic man: a case report.

PMID- 11225969
TI  - Lynx Therapeutics Inc. and Genomics Collaborative Inc. join forces.

PMID- 11225970
TI  - Antisense oligonucleotides for diabetes.

PMID- 11225971
TI  - New gadgets and gismos.

PMID- 11225972
TI  - Non-thiazolidinedione insulin sensitiser shows promise.

PMID- 11225973
TI  - Hyperlipidemia and erectile dysfunction.
AB  - We have done consecutive studies to investigate the effects of impaired lipid
      metabolism on the contractile and relaxation response of cavernous smooth muscles
      and to elucidate its pathogenesis: 1) incidence of hyperlipidemia in impotent
      patients; 2) erection response to intracavernous injection of papaverine in
      impotent patients with hyperlipidemia; 3) relaxation responses of isolated
      cavernosal smooth muscles to endothelium-independent and endothelium-dependent
      vasodilators in impotent patients with hypercholesterolemia or
      hypertriglyceridemia; 4) involvement of superoxide radical in the impaired
      endothelium-dependent relaxation of cavernous smooth muscle in
      hypercholesterolemic rabbits; 5) effects of isolated lipoproteins and
      triglyceride, combined oxidized LDL plus triglyceride, and combined oxidized LDL
      plus HDL on contractile and relaxation response of rabbit cavernous smooth
      muscles; 6) involvement of e-NOS in the impaired endothelium-dependent relaxation
      of cavernous smooth muscle in hypercholesterolemic rabbit. Hypercholesterolemia
      may cause impairment of endothelium-dependent relaxation. Oxidized LDL is the
      major causative cholesterol of the impaired relaxation response. A chain
      reaction, the production of superoxide radicals and functional impairment of eNOS
      may be a major cause of the functional impairment in the early stages of
      hypercholesterolemia.

PMID- 11225974
TI  - Mapping of metastasis suppressor genes for prostate cancer by microcell-mediated
      chromosome transfer.
AB  - AIM: To identify the metastasis suppressor genes for prostate cancer. METHODS: A
      copy of human chromosomes was introduced into the highly metastatic Dunning R
      3327 rat prostate cancer cells by the use of microcell-mediated chromosome
      transfer. Relationships between the size of human chromosomes introduced into
      microcell hybrid clones and the number of lung metastases produced by the clones
      were analyzed to determine which part of human chromosomes contained the
      metastasis suppressor gene(s) for prostate cancer. To determine portions of human
      chromosomes introduced, G-banding chromosomal analysis, fluorescence in situ
      hybridization analysis, and polymerase chain reaction analysis were performed.
      RESULTS: Each of microcell hybrid clones containing human chromosomes 7, 8, 10,
      11, 12, or 17 showed decreased ability to metastasize to the lung without any
      loss of tumorigenicity. This demonstrates that these human chromosomes contain
      metastasis suppressor genes for prostate cancer. Spontaneous deletion of portions
      of human chromosomes was observed in the human chromosome 7, 10, 11, 12, and 17
      studies. In the human chromosome 8 study, irradiated microcell-mediated
      chromosome transfer was performed to enrich chromosomal arm deletions of human
      chromosome 8. Molecular and cytogenetic analyses of microcell hybrid clones
      demonstrated that metastasis suppressor genes on human chromosomes were located
      on 7q21-22, 7q31.2-32, 8p21-12, 10q11-22, 11p13-11.2, 12p11-q13, 12q24-ter, and
      17pter-q23. KAI1 and MKK4/SEKI were identified as metastasis suppressor genes
      from 11p11.2 and 17p12, respectively. CONCLUSION: This assay system is useful to
      identify metastasis suppressor gene (s) for prostate cancer.

PMID- 11225975
TI  - The human acrosome reaction.
AB  - We developed tests of sperm-oocyte interaction: sperm-zona binding, zona-induced
      acrosome reaction, spermzona penetration and sperm-oolemma binding, using oocytes
      which failed to fertilise in clinical in vitro fertilization (IVF). Although
      oocyte defects contribute to failure of sperm oocyte interaction, rarely are all
      oocytes from one woman affected. Low or zero fertilization in standard IVF was
      usually caused by sperm abnormalities. Poor sperm-zona pellucida binding was
      frequently associated with failure of standard IVF and obvious defects of sperm
      motility or morphology. The size and shape of the acrosome is particularly
      important for sperm binding to the oocyte. The proportion of acrosome intact
      sperm in the insemination medium was related to the IVF rate. Inducing the
      acrosome reaction with a calcium ionophore reduced sperm-zona binding. Blocking
      acrosome dispersal with an acrosin inhibitor prevented spermzona penetration.
      Sperm-zona penetration was even more highly related to IVF rates than was sperm
      zona binding. Some patients had low or zero fertilization rates with standard IVF
      but normal sperm by conventional tests and normal sperm-zona binding. Few of
      their sperm underwent the acrosome reaction on the surface of the zona and none
      penetrated the zona. In contrast, fertilization and pregnancy rates were high
      with intracytoplasmic sperm injection. We call this condition defective zona
      pellucida induced acrosome reaction. Discovery of the nature of the abnormalities
      in the signal transduction and effector pathways of the human zona pellucida
      induced acrosome reaction should result in simpler tests and treatments for the
      patients and also provide new leads for contraceptive development.

PMID- 11225976
TI  - Constraints in the development of contraceptives for men.
AB  - Considerable efforts have been made to develop a male contraceptive and the
      studies have provided very useful information in this field. At least five
      different strategies to develop a male contraceptive have been pursued, namely:
      inhibition of sperm production, interference with sperm function, interruption of
      sperm transport, prevention of sperm deposition, and prevention of sperm-egg
      interaction. Of all these approaches, inhibition of sperm production by using
      androgens either alone or in combination with progestins have given the most
      encouraging results. A number of clinical trials substantiate that it is indeed
      possible to have a reversible, effective and safe hormonal method of
      contraception. A postmeiotic and epididymal approach to interfere with sperm
      function or the secretory and metabolic processes of the epididymis is another
      attractive option of male contraceptive development. A number of chemical
      compounds have been identified which interfere with sperm function in the
      epididymis without affecting sperm production, however, the compounds evaluated
      so far were found to be toxic. Interruption of sperm transport through the vas
      either by vasectomy or percutaneous intravasal injection of liquids which form
      cure-in-place plugs is also an attractive option. However, reversibility of the
      methods is of concern in their wide scale use. The major constraint in developing
      a long-acting male contraceptive seems to be the need for greater investment for
      product development. The clinical trials for evaluating the efficacy and safety
      of the new products and formulations stretch over several years and require
      enormous financial commitment. Nevertheless, the long-term gain of having a long
      acting reversible contraceptive for men is far greater than the financial
      commitments over few years. Male attitude towards using methods of family
      planning is much more favourable than originally believed. The pharmaceutical
      industry as well as the health care providers therefore have a greater
      responsibility. For early development of a contraceptive for men, it is essential
      to increase investment and simplify the drug regulatory procedures. The advent of
      newer technologies coupled with the convergent efforts of scientists will
      certainly make it possible to have an effective, safe and reversible male
      contraceptive in the near future.

PMID- 11225977
TI  - Studies on relationship between testicular capsule and sperm transport in rat
      testis.
AB  - AIM: In SD rats, histological changes in the testis were observed after bilateral
      capsulotomy (of the tunica albuginea) in order to investigate the physiological
      role of the testicular capsule on sperm transport. METHODS: Bilateral
      longitudinal capsulotomy was devised to disrupt the capsular contractile
      function. With this technique, only the tunica vaginalis and tunica albuginea
      were slit open, leaving the tunica vasculosa intact to embrace the underlying
      testicular parenchyma. After capsulotomy, the structural changes in the
      seminiferous tubules, the transitional distal seminiferous segment, and the rete
      testis were observed. RESULTS: In the capsulotomized testis, there was sperm
      retention at the transitional seminiferous segment and progressive degenerative
      changes in seminiferous tubules. CONCLUSION: The results clearly indicated that
      an intact testicular capsule was required for normal sperm transport from the
      seminiferous tubules into the rete testis. This is the first attempt to study the
      physiological role of the testicular capsule in intact animals.

PMID- 11225978
TI  - Probability to retrieve testicular spermatozoa in azoospermic patients.
AB  - AIM: The degree of probability to retrieve spermatozoa from testicular tissue for
      intracytoplasmic sperm injection into oocytes is of interest for counselling of
      infertility patients. We investigated the relation of sperm retrieval to clinical
      data and histological pattern in testicular biopsies from azoospermic patients.
      METHODS: In 264 testicular biopsies from 142 azoospermic patients, the testicular
      tissue was shredded to separate the spermatozoa, histological semi-thin sections
      of which were then evaluated using Johnsen score. RESULTS: The retrieval of
      spermatozoa correlated significantly ( P < 0.001) with the testicular volume ( r
      = 0.49), the FSH concentration ( r = -0.66), the maximum score (r = 0.85) and the
      mean Johnsen score (r = 0.81). In the multivariate regression analysis the
      successful testicular sperm extraction showed the closest relationship to the
      maximum score. The testicular volume correlated significantly with the mean
      Johnsen score ( r = 0. 64, P < 0. 001), and the basal serum FSH concentration
      mainly with the maximum score ( r = - 0.77; P < 0.001). Patients with a history
      cryptorchidism showed a significantly lower Johnsen score compared to the
      patients who did not have any testicular disease in the past (3.7 +/- 2.4 vs. 5.9
      +/- 2.5; P < 0. 01). CONCLUSION: In a limited range, the testicular volume and
      the FSH concentration in serum were related to the Johnsen score which correlated
      significantly with the sperm retrieval. The successful sperm retrieval can be
      expected in all azoospermic patients irrespective of the results of clinical
      examination. However, the probability of retrieval of spermatozoa decreased
      significantly in patients with a FSH level > 18 U/L, testicular volume < 5 mL,
      mean Johnsen score <5, and maximum Johnsen score <7.

PMID- 11225979
TI  - Reversible effect of testosterone undecanoate injection on spermatogenesis in
      rats.
AB  - AIM: To study the effect of testosterone undecanoate (TU) injection on
      spermatogenesis in rats. METHODS: Twenty adult SD rats received vehicle or TU (8
      mg/kg, 19 mg/kg or 625 mg/kg) injection, im, every 15 days for 60 days, and
      another 38 animals received similar treatments for 130 days with half of them
      undergoing a recovery phase of 120 days (5 rats for each treatment). At the end
      of the treatment, testes were removed and the diameter of the seminiferous
      tubules and the number of late elongated spermatids (steps 15-19) per testis were
      estimated with stereological methods as a measure of the spermatogenic
      efficiency. RESULTS: Low dose (8 mg/kg) TU treatment virtually had no effect on
      spermatogenesis. A dose of 19 mg/kg slightly suppressed spermatogenesis 60 days
      after treatment, and severe suppression occurred after another 70 days of dosing.
      Spermatogenesis was completely recovered at the end of the recovery phase. Large
      dose (625 mg/kg) TU treatment did not significantly affect spermatogenesis and
      was well tolerated by animals. CONCLUSION: TU injection reversibly suppresses
      spermatogenesis in rats.

PMID- 11225980
TI  - Effects of Terminalia catappa seeds on sexual behaviour and fertility of male
      rats.
AB  - AIM: To evaluate the aphrodisiac potential of Tenminalia catappa Linn. seeds
      using a suspension of its kernel (SS) in 1% methyl cellulose in rats. METHODS:
      Male rats were orally treated with 1,500 mg/kg or 3,000 mg/kg SS or vehicle, and
      their sexual behaviour was monitored 3 h later using a receptive female. Another
      group of rats was orally treated with either 3,000 mg/kg SS or vehicle for 7
      consecutive days. Their sexual behaviour and fertility were evaluated on days 1,
      4 and 7 of treatment and day 7 post-treatment by pairing overnight with a pro
      oestrous female. RESULTS: The 1,500 mg/kg dose, had a marked aphrodisiac action
      (prolongation of ejaculation latency) but no effect on libido (% mounting, %
      intromission and % ejaculation), sexual vigour (mounting-and-intromission
      frequency), or sexual performance (intercopulatory interval). In contrast, the
      higher dose (3,000 mg/kg) reversibly inhibited all the parameters of sexual
      behaviour other than mounting-and-intromission frequency and copulatory
      efficiency. The effects of high dose SS were not due to general toxicity, liver
      toxicity, haemotoxicity, stress, muscle deficiency, muscle incoordination,
      analgesia, hypoglycaemia or reduction in blood testosterone level. They were due
      to marked sedation. CONCLUSION: The kernel of T. catappa seeds has aphrodisiac
      activity and may be useful in the treatment of certain forms of sexual
      inadequacies, such as premature ejaculation.

PMID- 11225981
TI  - KAI1/CD82 gene expression in benign prostatic hyperplasia and late-stage prostate
      cancer in Chinese.
AB  - AIM: To evaluate KAI1/CD82 expression in Chinese patients with benign prostatic
      hyperplasia (BPH) and late-stage carcinoma of prostate (CaP). METHODS: Thirty
      Chinese patients with benign prostatic hyperplasia and 34 with CaP
      (adenocarcinoma clinical stage C and D) were analyzed by means of
      immunohistochemical methods. RESULTS: The KAI1/CD82 expression in BPH tissue was
      all positive, which was uniformly located on the glandular cell membrane at the
      cell-to-cell borders, but KAI1/CD82 expression in metastasis CaP tissues was
      either significantly lower than that of BPH or negative, and the immunostaining
      pattern was not continuous. In late-stage CaP KAI1/CD82 expression was correlated
      inversely to the pathological grade ( P < 0.05), but not to clinical stage ( P >
      0.05). CONCLUSION: The authors believe that decreased and negative KAI1/CD82
      expression in late-stage CaP may be related to tumor progression and metastasis,
      and appears to be a prognostic marker.

PMID- 11225982
TI  - Status of vitamin E and reduced glutathione in semen of oligozoospermic and
      azoospermic patients.
AB  - AIM: To investigate the status of seminal plasma reduced glutathione (GSH) and
      vitamin E in three different conditions of spermatogenesis: azoospermia,
      oligozoospermia and normospermia. METHODS: Reduced glutathione was measured in
      the seminal plasma by the method of Moron et al (1979), and vitamin E estimation
      was performed by the method of Taylor et al (1976). RESULTS: Vitamin E levels in
      seminal plasma of oligospermic and azoospermic samples were significantly
      decreased to 65.54% and 66.04% respectively as compared to the normospermic
      group. Levels of reduced glutathione were also significantly decreased in
      oligospermic and azoospermic group, and the reduction in azoospermic group
      (76.73%) was more pronounced than oligozoospermic group (62.07%). CONCLUSION: The
      decrease in reduced glutathione, an endogenous antioxidant, levels in azoospermic
      and oligozoospermic conditions may cause disruption in the membrane integrity of
      spermatozoa as a consequence of increased oxidative stress.

PMID- 11225983
TI  - Determination of sperm acrosin activity for evaluation of male fertility.
AB  - AIM: To investigate a simple method for assaying acrosin activity for the
      evaluation of male fertility. METHODS: The acrosin activity of 7.5 x 10(6) sperm
      without seminal plasma and acrosin activity inhibitors was assayed using N-alpha
      benzoyl-DL-arginine-p-nitroanilide (BAPNA) and detergent (Triton X-100) as
      substrate. RESULTS: The acrosin activity of 60 normal fertile men (35 +/- 10
      microIU/10(6) sperm ) was higher than that of 168 infertile men (16 +/- 8
      microIU/10(6) sperm) (P < 0. 01). It was indicated that there was a significant
      positive correlation between the acrosin activity and the sperm motility (r > or
      = 0.6534, P < 0.01) and a significant negative correlation between the sperm
      malformed rate and the WBC number (r < or = -0.5426, P < 0.01). The temperature
      and time of incubation and the sperm concentration could influence the assay
      results. CONCLUSION: Acrosin activity is an important index for the evaluation of
      male fertility. The approach developed by the authors is a simple method for the
      determination of acrosin activity.

PMID- 11225984
TI  - Evaluation of transurethral application of alprostadil for erectile dysfunction
      in Indonesians.
AB  - AIM: To evaluate the efficacy and safety of transurethral application of
      alprostadil (MUSE) for the treatment of erectile dysfunction in Indonesians.
      METHODS: Twenty erectile dysfunction patients aged between 32-74 years old were
      recruited in this study. The inclusion criteria were as follows: 1) adult males
      18 years or older with a subjective complaint or erectile dysfunction, 2) to
      provide written informed consent, 3) to agree not to use other forms of treatment
      for erectile dysfunction, 4) fulfill the screening laboratory values. Part 1,
      eligible patients were titrated in the clinic starting with a dose of 250 microg
      and proceed in a stepwise manner to 500 microg and 1,000 microg on separate
      clinic visits until they identified a dose that produced a satisfactory response.
      The interval between each in-clinic titration was 2-3 days. Each in-clinic
      titration dose was evaluated at 15 min intervals over a one hour period for
      erection assessment, blood pressure and pulse. Part 2, patients used MUSE at home
      for three months at the dose identified during the in-clinic titration. Monthly
      interim visits were required for patient follow-up and drug distribution. At the
      end of the study, patients had another laboratory (except testosterone, only
      assayed in screening procedure) and physical examination. RESULTS: The etiology
      of erectile dysfunction was psychological in 5 patients and organic in 15
      patients. The 65% of the patients achieved the erection scale of 4 or 5 either in
      the clinic or at home, 10% achieved the scale of 4 at home, but not in the
      clinic, and 25% only achieved the scale of 2 or 3 with the highest dose of 1,000
      microg either in the clinic or at home. No significant differences were found in
      biochemical examination before and after the study. The 60% of the patients who
      achieved erection scale 4 or 5 continued to use MUSE until the end of the study,
      while 40% of them complained of pain at the time of MUSE application, during
      erection and/or during intercourse. They withdrew from the study. CONCLUSION:
      Transurethral application of alprostadil (MUSE) is effective and safe to produce
      erection sufficient for intercourse in erectile dysfunction of various
      etiologies. Pain during application, erection and intercourse is a common side
      effect and a cause of withdrawal.

PMID- 11225985
TI  - Re: Letter to the editor: Handelsman DJ and Wu FCW, Asian Joural of Andrology,
      2000; (2): 78.

PMID- 11225986
TI  - Re: Unwarranted demand for body parts of endangered animal species for treatment
      of male infertility (Asian J Andorl 2000; 2:158).

PMID- 11225987
TI  - A summary of the Third Asian and Oceanic Congress of Andrology.

PMID- 11225988
TI  - Tumour-induced suppression of immune response and its correction.
AB  - Immunosuppressive features of tumour cells are a major obstacle for immunotherapy
      of cancer. We recently noted that RENCA cells effectively interfere with the in
      vivo activation of RENCA-specific T cells. To unravel the underlying mechanism,
      we evaluated the influence of RENCA cells on a mixed-lymphocyte/ tumour reaction
      as well as an allogeneic mixed-lymphocyte reaction. We observed that RENCA cells
      were not directly immunosuppressive. Instead, they initiated deviation of an
      immune response in at least two independent directions: (i) expansion of a
      population of NK1.1+/CD3+ cells, which was accompanied by elimination of mainly
      CD4+ lymphocytes, and (ii) production of a leukocyte-derived inhibitory factor.
      Expression of the costimulatory molecule B7.1 by RENCA cells prevented induction
      of anergy, while expression of MHC class II molecules prevented expansion of
      NK1.1+ cells, which was accompanied by a significant decrease in cell death.
      Hence, an unimpaired response was observed only when RENCA cells expressed B7.1
      plus MHC class II molecules. Thus, even if a tumour itself is not
      immunosuppressive, it can induce a strong deviation of the immune response. It is
      concluded that the first contact between elements of the immune system and the
      tumour cell can confer a severe bias on immunoregulatory circuits.

PMID- 11225989
TI  - The murine CC chemokine, 6C-kine, inhibits tumor growth and angiogenesis in a
      human lung cancer SCID mouse model.
AB  - The recently described CC chemokine, 6C-kine, is unique in that it contains -six
      rather than the usual four conserved cysteines typical of this family.
      Furthermore, murine 6C-kine binds to one of the CXC chemokine receptors CXCR3, in
      addition to its other known receptor CCR7. We have shown that two other ligands
      of CXCR3, IP-10 and MIG, are potent inhibitors of tumor growth in severe combined
      immunodeficiency (SCID) mice. We postulated that murine 6C-kine may also inhibit
      tumor growth via inhibition of angiogenesis in this model. SCID mice (n = 6 per
      group) inoculated with A549 human lung cancer cells were treated with either 6C
      kine (100 ng intra-tumor injection every other day) or control protein for 8
      weeks. Tumors from murine 6C-kine-treated mice (288 +/- 26 mm3) were
      significantly smaller than tumors from control treated mice (788 +/- 156 mm3, P =
      0.005). Additionally, murine 6C-kine reduced metastases compared with controls
      (0.5 +/- 0.3 vs 3.0 +/- 1.2 metastases per animal, P = 0.05). Tumor vascularity
      (as assessed by vessel density counting) was reduced in murine 6C-kine-treated
      mice compared with controls. Murine 6C-kine had no direct effect on proliferation
      of A549 cells, and there were no differences in the infiltration of leukocyte sub
      populations, assessed by flow cytometry, in the treatment groups. Interestingly,
      human 6C-kine, unlike murine 6C-kine, does not bind CXCR3 and had no anti-tumor
      effect in the same model. These data suggest that murine 6Ckine has anti-tumor
      effects independent of its leukocyte-recruiting activity. Furthermore, while not
      confirmatory, these data lend further support to the fact that CXCR3 may be the
      receptor for angiostatic CXC chemokines.

PMID- 11225990
TI  - Induction of cytolytic T lymphocytes by immunization of mice with an adenovirus
      containing a mouse homolog of the human MAGE-A genes.
AB  - The genes of the MAGE-A family code for antigens that are strictly tumor-specific
      and are shared by many human tumors. Melanoma patients have been immunized
      against these antigens and some tumor regressions have been observed. However, no
      unequivocal evidence of cytolytic T cell responses has been obtained by analyzing
      the blood lymphocytes of these patients. Hence it was considered worthwhile to
      examine in mouse systems whether or not immunization against antigens derived
      from the mouse Mage homologs can produce cytolytic T cell responses. We have
      identified an antigenic peptide encoded by mouse gene Mage-a2, and here we show
      that immunization of DBA/2 mice with a recombinant adenovirus containing either
      just the sequence encoding this peptide or a large part of the Mage-a2 coding
      sequence produces strong cytolytic T cell responses. The Mage-a2 system should
      prove useful for the comparison of vaccination modalities that could be applied
      to human patients in therapeutic vaccination trials with MAGE antigens.

PMID- 11225991
TI  - Characterization of CD8+ cytotoxic T lymphocyte/tumor cell interactions
      reflecting recognition of an endogenously expressed murine wild-type p53
      determinant.
AB  - p53 mutations are frequently found in human cancers and are often associated with
      the overexpression of wild-type (WT) protein or peptide sequences, supporting the
      notion that WT p53 epitopes may serve as potential targets for tumor
      immunotherapy. We have developed a cytotoxic T lymphocyte (CTL)/p53 tumor
      associated antigen (TAA) model, based on immune recognition of a WT p53
      determinant. WT p53-peptide-specific, major histocompatibility complex (MHC)
      classI-restricted CTL were produced from immunocompetent C57BL/6 (H-2b) mice
      after immunization with a previously defined WT p53 peptide (p53(232-240))
      Epitope-specific CTL were then employed to identify syngeneic tumor cell
      populations expressing that antigenic determinant. Two syngeneic tumor cell
      lines, MC38 colon carcinoma and MC57G fibrosarcoma, were demonstrated to express
      the endogenous WT p53(232-240) determinant naturally, as defined by CD8 + CTL
      recognition. Cold-target inhibition assays confirmed that CTL-mediated lysis was
      due to immune recognition of the p53(232-240) peptide epitope. The p53(232-240)
      specific CTL line did not lyse syngeneic normal cells (i.e., mitogen-activated
      splenocytes) in the absence of exogenous peptide, suggesting that the WT-p53
      specific CTL could distinguish between tumor cells expressing self-TAA and normal
      host cells. We have demonstrated, for the first time, that the adoptive transfer
      of WT-p53-specific CTL to mice with established pulmonary metastasis resulted in
      antitumor activity in vivo. The ability to generate MHC-class-I-restricted CD8-
      CTL lines specific for a non-mutated p53 determinant from normal, immunocompetent
      mice, which display antitumor activity both in vitro and in vivo (by adoptive
      transfer), may have implications for the immunotherapy of certain p53-expressing
      malignancies.

PMID- 11225992
TI  - Granulocyte/macrophage-colony-stimulating-factor plus interleukin-2 plus
      interferon alpha in the treatment of metastatic renal cell carcinoma: a pilot
      study.
AB  - Granulocyte/macrophage-colony-stimulating factor (GM-CSF) plays a central role in
      the differentiation and function of dendritic cells, which are crucial for the
      elicitation of MHC-restricted T cell responses. Preclinical and the first
      clinical data provide a rationale for the application of GM-CSF in immunotherapy
      of cancer. Ten patients with renal cell carcinoma stage IV (Holland/ Robson) were
      treated in this pilot study. Therapy was started with GM-CSF alone (2 weeks).
      Interleukin (IL-2) and interferon alpha (IFNalpha) were added sequentially (3
      weeks GM-CSF plus IL-2 or IFNalpha, 3 weeks GM-CSF plus IL-2 plus IFNalpha).
      Therapy was performed on an outpatient basis. The cytokine regimen was evaluated
      for toxicity, clinical response and immunomodulatory effects [fluorescence
      activated cell sorting analysis of peripheral blood mononuclear cells (PBMC),
      mixed-lymphocyte reaction and cytotoxicity of PBMC]. GM-CSF treatment caused a
      significant increase in the number of PBMC expressing costimulatory molecules.
      Addition of IL-2 and IFNalpha led to an increase in CD3 , CD4+, CD8+ and CD56+
      PBMC in week 9. In an autologous mixed-lymphocyte reaction a 2.1-fold increase in
      T cell proliferation was observed after 2 weeks of GM-CSF treatment, and
      cytotoxicity assays showed changes in natural-killer-(NK)- and non-NK-mediated
      cytotoxicity in some patients. Two patients achieved partial remission, one
      patient had a mixed response. The toxicity of the regimen was mild to moderate
      with fever, flu-like symptoms and nausea being observed in most patients. Severe
      organ toxicity was not observed. We conclude that GM-CSF might be useful for
      immunotherapy of renal cell carcinoma, especially in combination with T-cell
      active cytokines. Further studies are warranted.

PMID- 11225993
TI  - Multiple mechanisms of immune evasion can coexist in melanoma tumor cell lines
      derived from the same patient.
AB  - Progressive tumor growth may be associated with suppression of the immune
      response. Many different mechanisms may contribute to immune evasion. We
      investigated some of these mechanisms in melanoma cells lines generated from two
      patients. These cell lines show a complex pattern of altered HLA expression;
      however, the resulting phenotype did not satisfactorily explain the simultaneous
      evasion of T and NK cell cytotoxicity. Two additional alterations have now been
      detected in these melanoma cell lines: (1) resistance to FAS-induced apoptosis
      caused by defective FAS gene expression, and (2) constitutive expression of
      immunosuppressive cytokines. Our results show that several of the major
      mechanisms for immune evasion may coexist in a single tumor. This suggests that
      tumor progression may give rise to an extremely resistant phenotype, which may be
      an impediment to some immunotherapeutic strategies. We hypothesize that the
      simultaneous presence of several mechanisms involved in tumor immune evasion must
      be the result of progressive selection of characteristics that are advantageous
      for tumor survival in a competent host. Our findings do not support the
      possibility that FASL expression is a common mechanism of evasion of immune
      response in melanoma cells.

PMID- 11225995
TI  - CD20: a gene in search of a function.
AB  - CD20 is a signature B-cell differentiation antigen. The function of CD20 is
      unknown, although it is thought to be involved in B-cell activation, regulation
      of B-cell growth, and transmembrane calcium flux. This review covers several
      topics important for understanding CD20 biology. These topics include the
      expression pattern and transcriptional regulation of the CD20 gene, the structure
      of the protein and its interaction with other cell surface molecules, as well as
      CD20 phosphorylation and putative functions. An understanding of CD20 function
      from signal transduction to biological implications may prove important for the
      mechanistic understanding of the treatment of certain types of cancer.

PMID- 11225994
TI  - Immunogenetic therapy for B-cell malignancies.
AB  - Neoplastic B cells are stealthlike in their ability to evade immune detection,
      even by allogeneic T cells of normal healthy donors. This stealthlike phenotype
      can be reversed by activating neoplastic B cells through ligation of CD40, a cell
      surface molecule that can interact with a ligand expressed on activated T cells.
      The gene encoding this ligand, CD154, can be transferred into neoplastic B cells
      ex vivo through infection with a modified adenovirus vector called Ad-CD154. This
      results in a dramatic change in the phenotype and function of the neoplastic B
      cells. Infected malignant B cells can stimulate T cells reactive with potential
      tumor antigens and induce autologous cytotoxic T cells capable of destroying the
      neoplastic B cells in vitro. This formed the basis for an immune gene therapy
      protocol in which patients were infused with Ad-CD154-transduced leukemic B
      cells. Treatment was well tolerated, without apparent long-term toxicity, and
      without a maximum tolerated dose. Biologic and clinical responses were observed,
      including significant reductions in leukemia cell counts and lymph node sizes
      after a single one-time infusion. Furthermore, preliminary data suggest that this
      approach can enhance antibody-dependent cellular cytotoxicity and thereby augment
      the activity of antitumor monoclonal antibody therapy. Development of such
      strategies may allow for effective immunogenetic therapy for B-cell malignancies.

PMID- 11225996
TI  - Current therapeutic paradigm for the treatment of non-Hodgkin's lymphoma.
AB  - Patients with indolent non-Hodgkin's lymphoma may be treated with various
      approaches ranging from deferred initial therapy (watch and wait) to single-agent
      alkylating agents, radiation therapy, or combination chemotherapy. None of these
      approaches have produced curative results. Clearly, innovative treatment
      strategies are needed. The use of interferon, monoclonal antibodies with or
      without radioisotopes, purine analogues, and even high-dose therapy with stem
      cell rescue are under investigation. Based on the fact that fewer than 40% of
      advanced-stage, aggressive non-Hodgkin's lymphoma patients are cured with
      cyclophosphamide/doxorubicin/vincristine/prednisone chemotherapy, the best
      approach for any patient is an experimental one. Examples include: (1) increasing
      the dose intensity of drugs used in standard regimens; (2) preventing the
      development of drug resistance; (3) combining monoclonal antibodies with
      chemotherapy; or (4) autologous stem-cell transplantation as a rescue from marrow
      ablative chemotherapy. If a patient is not eligible or does not wish to
      participate in a clinical trial,
      cyclophosphamide/doxorubicin/vincristine/prednisone, as inadequate as it is,
      remains the gold standard.

PMID- 11225997
TI  - Rituximab as first-line systemic therapy for patients with low-grade lymphoma.
AB  - Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA and IDEC
      Pharmaceutical Corporation, San Diego, CA), the first monoclonal antibody
      available for the systemic treatment of cancer, yields a 48% response rate in
      patients with refractory low-grade non-Hodgkin's lymphoma. This preliminary
      report describes the use of rituximab, instead of standard chemotherapy, in 39
      previously untreated patients with stages II-IV low-grade non-Hodgkin's lymphoma
      All patients received rituximab 375 mg/m2 by intravenous infusion for 4
      consecutive weeks and were evaluated for response at week 6. Patients with stable
      disease or an objective response received repeat 4-week courses at 6-month
      intervals, for a maximum of four treatment cycles. At initial evaluation for
      response at week 6, 21 of 39 patients (54%) had objective responses and 14 (36%)
      had stable disease or a minor response. Response rates were similar in patients
      with follicular and small lymphocytic lymphoma (52% v 57%, respectively). Seven
      additional responses were reported either before or after the second course.
      Currently, the overall response rate is 72%, with 18% complete responses. The
      progression-free survival rate at 1 year is 77%. Treatment was well tolerated.
      The high level of activity suggests that initial treatment with rituximab is a
      reasonable option in this group of patients, and that repeat maintenance courses
      at 6-month intervals are feasible and well tolerated. Further follow-up
      evaluation is necessary to determine the merits of this approach compared with
      traditional chemotherapeutic treatment.

PMID- 11225998
TI  - Chemotherapy sensitization by rituximab: experimental and clinical evidence.
AB  - For most lymphomas, chemotherapy is palliative because of an inability to
      overcome drug resistance within the lymphoma cells and attempts at overcoming
      specific drug resistance mechanisms, such as multidrug resistance, have had
      limited success. However, accumulating evidence suggests that the ability to
      activate apoptotic pathways may be an important determinant of chemotherapy
      sensitivity and presents a potentially important new therapeutic strategy.
      Studies have shown that distinct cellular thresholds exist for apoptosis, and it
      is likely that multiple developmental and environmental factors converge in a
      dynamic process to regulate this set point. If the threshold for inducing
      apoptosis is limiting, then strategies to modulate these pathways may profoundly
      enhance the efficacy of cytotoxic therapy. Monoclonal antibodies against the CD20
      receptor have been shown to directly induce apoptosis and may serve to modulate
      the threshold for chemotherapy-induced apoptosis. Recent clinical studies of the
      monoclonal antibody, rituximab (Rituxan; Genentech, Inc, South San Francisco, CA
      and IDEC Pharmaceutical Corporation, San Diego, CA), and combination chemotherapy
      have produced unexpectedly high rates of response and progression-free survival,
      suggesting rituximab improves the efficacy of chemotherapy. Taken together, the
      results from in vitro and clinical studies suggest that rituximab may modulate
      the sensitivity of B-cell lymphomas to chemotherapy.

PMID- 11225999
TI  - Safety of fludarabine, mitoxantrone, and dexamethasone combined with rituximab in
      the treatment of stage IV indolent lymphoma.
AB  - Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA and IDEC
      Pharmaceutical Corporation, San Diego, CA) is an effective agent for the
      treatment of CD20-positive B-cell lymphomas. Because its toxicities are minimal
      and do not overlap with the toxicities of standard chemotherapy, it is an
      appealing agent to use in combination with chemotherapy. Moreover, there is
      evidence for synergy between rituximab and some chemotherapeutic agents. The
      combination of fludarabine/ mitoxantrone/dexamethasone (FND) has been a well
      tolerated and effective regimen for the treatment of indolent lymphomas. When
      given together with prophylaxis for Pneumocystis carinii, infectious
      complications with FND have been modest. We report on preliminary safety data
      using FND in conjunction with rituximab, along with maintenance alpha interferon.
      Toxicity has been modest. The concurrent use of rituximab with FND modestly
      increases neutropenia, but has not resulted in any change in the pattern of
      infectious or other toxicity that occurs with FND alone.

PMID- 11226000
TI  - Molecular diagnostics in follicular non-Hodgkin's lymphoma: a review.
AB  - Follicular lymphoma is a low-grade, indolent non-Hodgkin's lymphoma characterized
      by the presence of the t(14;18) translocation. The detection of this
      translocation using polymerase chain reaction techniques has been increasingly
      studied. However, the diagnostic and prognostic value of detecting t(14;18)
      rearrangements has been questioned. Translocation has been identified in a
      significant proportion of healthy donors and patients with nonmalignant diseases.
      Clearance of t(14;18) rearrangements following conventional treatments, purging
      of bone marrow/peripheral blood stem cells, and transplantation is associated
      with improved long-term outcome of patients with follicular lymphoma. Until
      randomized studies confirm the clinical utility of polymerase chain reaction
      detection of the translocation, emphasis should be placed on improving the
      accuracy and reproducibility of polymerase chain reaction techniques, and
      standardizing assays among laboratories.

PMID- 11226001
TI  - Optimizing the use of rituximab for treatment of B-cell non-Hodgkin's lymphoma: a
      benefit-risk update.
AB  - Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA and IDEC
      Pharmaceutical Corporation, San Diego, CA), the first monoclonal antibody
      approved in the United States for the treatment of cancer, is indicated for the
      treatment of patients with relapsed or refractory CD20+ low-grade non-Hodgkin's
      lymphoma. From November 1997 through May 1999, approximately 36,000 patients have
      been treated with rituximab. Serious cardiopulmonary infusion reactions
      culminating in death have been reported to occur in approximately 0.04% to 0.07%
      of patients. Post-approval tumor lysis syndrome has been reported within 12 to 24
      hours after the first antibody infusion and is estimated to occur in 0.04% to
      0.05% of patients. The risk of tumor lysis appears to be higher in patients with
      high numbers of circulating malignant cells. Serious infusion-related adverse
      drug reactions, most often consisting of cardiopulmonary reactions associated
      with the rapid lysis of large numbers of circulating malignant cells, have been
      fatal in approximately 0.5 per 1,000 treated patients. Major risk factors include
      high numbers of circulating malignant lymphoma cells, pulmonary infiltrates or
      lymphoma involvement, and prior cardiovascular disease. This report updates the
      safety experience of rituximab therapy with data from clinical trials and
      postmarketing safety experience, and examines how this information can be used to
      optimize therapy.

PMID- 11226002
TI  - Principles of radioimmunotherapy for hematologists and oncologists.
AB  - Recent trials with radiolabeled monoclonal antibodies targeting lymphoid surface
      membrane antigens have shown high response rates and tolerable toxicity.
      Radiolabeled antibodies emit continuous, exponentially decreasing, low-dose-rate
      radiation, whereas conventional external-beam radiotherapy delivers intermittent,
      fractionated radiation at higher dose rates. The most common isotopes used for
      radioimmunotherapy (iodine 131 and yttrium 90) kill cells primarily by emission
      of beta particles (electrons), which are believed to induce DNA strand breaks.
      The beta particles of Y 90 are more energetic than those of I 131, and affect
      cells over a radius of 5 mm compared with 0.9 mm to 1.0 mm for I 131. In
      addition, I 131 emits long-range gamma rays that permit direct imaging with a
      gamma camera, but also deliver a whole-body radiation dose and may pose a risk to
      health care workers. Physical barriers to effective delivery of
      radioimmunotherapy include the heterogeneous tumor vasculature, slow diffusion
      and convection rates of large antibody molecules through the interstitial fluid,
      heterogeneous biodistribution of antibodies in tumor nodules, and high
      intratumoral pressures impeding antibody influx into tumors. Despite these
      obstacles, multiple trials have shown the efficacy of radioimmunotherapy,
      particularly for B-cell lymphomas treated with anti-CD20 antibodies, in which
      response rates of 60% to 90% have been reported.

PMID- 11226003
TI  - The use of ibritumomab tiuxetan radioimmunotherapy for patients with relapsed B
      cell non-Hodgkin's lymphoma.
AB  - Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA and IDEC
      Pharmaceutical Corporation, San Diego, CA) is a monoclonal antibody that targets
      the CD20 antigen present in most B-cell non-Hodgkin's lymphomas. Previous studies
      have shown overall response rates (ORR) of approximately 50% in relapsed
      patients. Ibritumomab is the murine parent anti-CD20 antibody that is linked
      through a MX-DTPA chelator to yttrium 90 (90Y) to form the radioimmunoconjugate
      90Y-ibritumomab tiuxetan (Zevalin; IDEC Pharmaceuticals, San Diego, CA). A phase
      I study of 90Y-ibritumomab tiuxetan determined that 0.4 mCi/kg was the maximum
      tolerated dose, and responses were reported in 67% of all patients and in 82% of
      patients with low-grade non-Hodgkin's lymphoma. A separate trial randomized
      eligible patients to either rituximab or 90Y-ibritumomab tiuxetan. An interim
      analysis of the first 90 patients showed an ORR of 80% with 90Y-ibritumomab
      tiuxetan versus 44% with rituximab (P < .05). A subsequent trial for patients
      with rituximab-refractory disease showed a 46% ORR. These studies show that 90Y
      ibritumomab tiuxetan is an active agent in relapsed non-Hodgkin's lymphoma and
      appears to have a higher ORR compared with unconjugated rituximab.

PMID- 11226004
TI  - The use of rituximab in the treatment of malignant and nonmalignant plasma cell
      disorders.
AB  - CD20 is a B-cell-restricted antigen that, for the most part, is expressed from
      the pre-B-cell to the mature B-cell stage of B-cell differentiation. Several
      transcription factors regulate CD20 expression during B-cell differentiation, the
      most important of which appear to be PU.1 and Pip (PU.1 interacting protein). As
      B cells differentiate to plasma cells, CD20 expression is down-regulated, which
      coincides with PU.1 downregulation in plasma cells. Analogous to their normal B
      cell counterparts, CD20 is expressed on malignant lymphoplasmacytic cells from
      most patients with Waldenstrom's macroglobulinemia and on malignant plasma cells
      from a fraction (20%) of multiple myeloma patients. CD20 also is expressed on
      subpopulations of normal donor plasma cells, which may include autoantibody
      secreting plasmacytes. In view of these findings, the anti-CD20 chimeric
      monoclonal antibody, rituximab (Rituxan; Genentech, Inc, South San Francisco, CA
      and IDEC Pharmaceutical Corporation, San Diego, CA), has been evaluated in the
      treatment of Waldenstrom's macroglobulinemia and multiple myeloma, as well as in
      nonmalignant plasma cell disorders including IgM polyneuropathies, immune
      thrombocytopenias, and autoimmune hemolytic anemias, with reported activity in
      these entities. An update of these clinical efforts is presented in this report.

PMID- 11226005
TI  - High-dose rituximab therapy in chronic lymphocytic leukemia.
AB  - Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA and IDEC
      Pharmaceutical Corporation, San Diego, CA) is a chimeric monoclonal antibody that
      targets mature B cells in most lymphoid B-cell malignancies. Rituximab is
      approved by the US Food and Drug Administration for therapy for recurrent B-cell
      lymphoma. In initial clinical trials the activity in small lymphocytic lymphoma,
      the counterpart of chronic lymphocytic leukemia (CLL), was less than 20%. In an
      attempt to increase the level of rituximab activity in CLL, we conducted a phase
      I dose-escalation study to overcome both the lower CD20 antigen density on CLL
      cells compared with lymphoma cells and the shorter half-life of rituximab in
      small lymphocytic lymphoma. Cohorts of patients were treated with escalated doses
      on weeks 2, 3, and 4 after an initial rituximab dose of 375 mg/m2 on day 1. The
      maximum dose of rituximab evaluated was 2,250 mg/m2. There is clear evidence of a
      dose-response relationship. Severe toxicity (grades 3 and 4) noted following the
      first dose of therapy in variant forms of CLL, namely mantle cell lymphoma and
      prolymphocytic leukemia, was uncommon in typical CLL. No unusual toxicity was
      noted at higher doses. Further exploration of the dosing schedule of rituximab in
      CLL and development of combination therapies is necessary. This agent shows
      promise for interaction in combined chemoimmunotherapy strategies for front-line
      and relapsed patients with CLL.

PMID- 11226006
TI  - Rituximab: an insider's historical perspective.
AB  - Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA and IDEC
      Pharmaceutical Corporation, San Diego, CA) is a unique monoclonal antibody for
      the treatment of non-Hodgkin's lymphoma. This chimeric mouse/human antibody was
      discovered in 1991 at IDEC Pharmaceuticals' laboratories, where the antibody was
      genetically engineered and produced utilizing high-yield expression systems. It
      is a human IgG1 kappa antibody with mouse variable regions isolated from a murine
      anti-CD20 antibody, IDEC-2B8, that binds with high affinity to cells expressing
      the CD20 antigen found on the surface of malignant and normal B cells, but not on
      other normal tissues. It mediates complement-dependent cell lysis in the presence
      of human complement, and antibody-dependent cellular cytotoxicity with human
      effector cells. Also, it has been shown to induce apoptosis and to sensitize
      chemoresistant human lymphoma cell lines in vitro. Clinical development was
      expedited (3 years) with the first patient entered in phase I trials in March
      1993 and the last patient entered in the phase III study in March 1996. IDEC
      Pharmaceuticals began a collaboration with Genentech, Inc in March 1995 and with
      F. Hoffman-LaRoche (Nutley, NJ) shortly thereafter. Marketing approval was
      granted by the US Food and Drug Administration on November 26, 1997 (and by the
      European Union on June 2, 1998) for the indication of relapsed or refractory,
      CD20-positive, B-cell, low-grade or follicular non-Hodgkin's lymphoma. Rituximab
      is the first therapeutic monoclonal antibody approved for the treatment of cancer
      and the first single agent approved specifically for therapy for a lymphoma.
      Substantial research has been performed over the past 8 years to further the
      understanding of this novel therapeutic. Nevertheless, much remains to be
      accomplished in key areas such as mechanism of action and resistance,
      combinations with chemotherapy, biologics and radiotherapy/radioimmunotherapy,
      role within multimodality regimens, and nonmalignant applications. Research
      conducted in the coming years should be targeted toward resolving these important
      issues.

PMID- 11226007
TI  - Overview of idiopathic thrombocytopenic purpura: new approach to refractory
      patients.
AB  - Idiopathic thrombocytopenic purpura is a disorder in which autoantibodies are
      made to platelets, resulting in accelerated platelet destruction. The diagnosis
      may be made in outpatients who are previously well or in patients with multiple
      medical conditions and medications. There are no unequivocal ways to distinguish
      immune thrombocytopenias from other thrombocytopenias, even with state-of-the-art
      tests including anti-platelet antibodies, thrombopoietin, glycocalicin, and
      platelet reticulocyte counts. Clinical evaluation includes ruling out a systemic
      process such as a viral infection or leukemia. Treatment of idiopathic
      thrombocytopenic purpura should be individualized. Substantial platelet increases
      are seen in more than 50% of patients who receive intravenous IgG, intravenous
      anti-D, steroids, or splenectomy. Two additional agents showing promising
      clinical trial experience are anti-CD40 ligand and rituximab (Rituxan; Genentech,
      Inc, South San Francisco, CA and IDEC Pharmaceutical Corporation, San Diego, CA).

PMID- 11226008
TI  - A pilot study of the anti-CD20 monoclonal antibody rituximab in patients with
      refractory immune thrombocytopenia.
AB  - We conducted a prospective pilot phase I/II clinical trial to evaluate the
      toxicity and response rate of the chimeric anti-CD20 monoclonal antibody,
      rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC
      Pharmaceutical Corporation, San Diego, CA), in the treatment of patients with
      immune thrombocytopenic purpura. Patients with a clinical diagnosis of idiopathic
      thrombocytopenic purpura who had failed corticosteroid therapy and whose platelet
      count was less than 75,000/microL were eligible for the study. Rituximab was
      administered in a dose-escalation fashion using doses ranging from 50 to 375
      mg/m2 weekly for 4 weeks. Thirteen patients have been enrolled on the trial to
      date and 12 have completed the full course of treatment. No unusual toxicity was
      noted in this patient population. None of the three patients at the lowest dose
      level achieved a clinical response. Three of nine patients (30%) who have
      received rituximab at doses close or equal to the full dose have shown an
      objective clinical response (two complete responses, one partial response). The
      study is currently ongoing, and conclusions regarding the overall response rate,
      clinical parameters that influence response, surrogate markers of response, and
      the underlying mechanism of response remain to be addressed. The current study
      should provide answers to a number of important questions regarding the role of
      rituximab in the treatment of this and other autoimmune disorders.

PMID- 11226009
TI  - How does time since feeding affect the fuels pigeons use during flight?
AB  - Time between meals can vary from multiple hours to days within and among species.
      We investigated the effects of time since feeding on lipid, protein, and
      carbohydrate oxidation in flying pigeons (Columba livia) by interpreting changes
      in blood plasma metabolite concentrations and mass during flight. Five pigeons
      were flown or rested for 4 h after food deprivations of 2, 12, 24, and 48 h.
      After flight, blood plasma concentrations of uric acid and beta-hydroxybutyrate
      were elevated over control and preflight values, indicating elevated protein and
      lipid catabolism during flight. Lipid oxidation, as indicated by changes in beta
      hydroxybutyrate concentration, increased more in unfed flying pigeons compared
      with recently fed flying pigeons and with resting controls. Protein oxidation, as
      indicated by changes in uric acid concentrations, also positively covaried with
      feeding time; the covariation was mostly caused by increases in 48-h food
      deprived pigeons. Unfed birds lost less mass during a 4-h flight than recently
      fed birds. We reasoned that recently fed pigeons oxidized more glycogen in flight
      than pigeons not recently fed; calculated glycogen stores explained 72%-117% of
      mass loss differences between 2- and 48-h-fed pigeons. Thus, time since feeding
      was an important determinant of the fuels pigeons used in flight.

PMID- 11226010
TI  - Variation in metabolic rate between populations of a geographically widespread
      lizard.
AB  - In geographically widespread ectotherms, variation in life history phenotypes may
      be caused by differences in maintenance metabolism of individuals. I estimated
      daily and annual maintenance metabolism of eastern fence lizards, Sceloporus
      undulatus, from two populations with markedly different life histories; lizards
      in South Carolina grow faster, mature earlier, and have greater annual
      reproductive output than lizards in New Jersey. I measured diel cycles of resting
      metabolic rate (RMR) at four temperatures (20 degrees, 30 degrees, 33 degrees,
      and 36 degrees C) during spring, summer, and fall. In all seasons, RMR increased
      significantly from 20 degrees to 33 degrees C but did not differ significantly
      between 33 degrees and 36 degrees C. Adults from New Jersey had a higher RMR than
      adults from South Carolina in summer and fall but not in spring. Juveniles from
      South Carolina had a higher RMR than juveniles from New Jersey in summer but not
      in spring or fall. Annual maintenance metabolism of New Jersey lizards (53.7 kJ)
      was greater than that of South Carolina lizards (45.8 kJ), despite the shorter
      duration of activity in New Jersey. I conclude that the difference in maintenance
      metabolism between populations contributes to the greater production by S.
      undulatus in South Carolina.

PMID- 11226011
TI  - Ion secretion by salt glands of desert iguanas (Dipsosaurus dorsalis).
AB  - Unlike the NaCl-secreting salt glands of many birds and reptiles, the nasal salt
      glands of lizards can secrete potassium as well as sodium, with either chloride
      or bicarbonate as the accompanying anion. The factors responsible for initiating
      secretion by the gland and the rates of cation and anion secretion were studied
      in the desert iguana, Dipsosaurus dorsalis. Lizards were given combinations of
      ions for several days, and secreted salt was collected daily and analyzed for
      sodium, potassium, chloride, and bicarbonate. Maximum total cation secretion rate
      was 4.4+/-0.38 micromol/g/d. Cation secretion ranged from 24% to 100% potassium;
      even high NaCl loads did not abolish potassium secretion. Maximum bicarbonate
      secretion was about 0.5 micromol/g/d; chloride was the predominant anion.
      Secretion rate increased only in response to those treatments that included
      potassium and/or chloride; sodium ions and other osmotic loads (e.g., sucrose)
      did not increase secretion. This is in contrast to birds and some other reptiles
      with salt glands, which initiate NaCl secretion in response to any osmotic load.
      The specificity of the response of the salt gland of Dipsosaurus may be related
      to the ecological importance of dietary potassium and chloride for herbivorous
      desert lizards.

PMID- 11226012
TI  - The beneficial acclimation hypothesis versus acclimation of specific traits:
      physiological change in water-stressed Manduca sexta caterpillars.
AB  - Do organisms make beneficial physiological adjustments in response to
      environmental change? We examined this question by measuring the effects of short
      term (12-36 h) and long-term (larval lifetime) hydric stress on the tobacco
      hornworm, Manduca sexta. Larvae were reared from the first instar on low-water
      (69%) or high-water (80%) artificial diets and then transferred early in the
      fifth instar to the same or opposite diet (2x2 design). Within the subsequent 36
      h, we measured 24-h growth rates and three primary determinants of the water
      budget: water gain via consumption and water loss via evaporation and defecation.
      Larvae preexposed to low-water diet grew less rapidly on low-water diet than
      those switched acutely to low-water diet from high-water diet, showing that
      larvae preexposed to a particular environment do not necessarily acclimate
      beneficially to that environment. Our data on water fluxes to and from larvae,
      however, strongly suggest that water-stressed larvae did make beneficial
      physiological adjustments. Larvae responded to short-term hydric stress by
      minimizing rates of water excretion, primarily by increasing rates of rectal
      water absorption. Larvae responded to chronic water stress by significantly
      reducing rates of evaporative water loss; they also showed additional reductions
      in fecal water excretion, but these decreases were due to lowered consumption and
      not to further increases in rate of rectal water absorption. This mismatch
      between maladaptive acclimation of organismal performance and beneficial
      adjustment of suborganismal traits can be reconciled by recognizing that
      organismal physiology is hierarchical: fitness-related performance traits
      represent the aggregate outcome of numerous, more mechanistic physiological
      traits. Although chronic exposure to an environment may depress the aggregate
      effect of these mechanistic traits on performance, organisms are not precluded
      from making beneficial adjustments to individual traits contributing to
      performance.

PMID- 11226013
TI  - Beta-adrenergic stimulation of volume-sensitive chloride transport in lamprey
      erythrocytes.
AB  - We measured the effects of a beta-adrenergic agonist, isoproterenol, on chloride
      transport and volume regulation of lamprey (Lampetra fluviatilis) erythrocytes in
      isotonic (288 mosm L(-1)) and hypotonic (192 mosm L(-1)) medium. Isoproterenol at
      a high concentration (10(-5) M) did not influence chloride transport in isotonic
      medium but markedly increased chloride fluxes in hypotonic conditions:
      unidirectional flux increased from 100 mmol kg dcw(-1) h(-1) in the absence to
      350 mmol kg dcw(-1) h(-1) (dcw=dry cell weight) in the presence of isoproterenol.
      Simultaneously, the half-time for volume recovery decreased from 27 to 9 min.
      Isoproterenol caused an increase in cellular cyclic AMP (cAMP) concentration. The
      stimulation of chloride transport in hypotonic conditions could be induced by
      application of the permeable cAMP analogue, 8-bromo-cyclic AMP, suggesting that
      the effect of beta-adrenergic stimulation on chloride transport occurs downstream
      of cAMP production. As isoproterenol did not affect unidirectional rubidium
      fluxes in hypotonic conditions, the transport pathway influenced by beta
      adrenergic stimulation is most likely the swelling-activated chloride channel.
      Because the beta-adrenergic agonist only influenced the transport in hypotonic
      conditions despite the fact that cAMP concentration also increased in isotonic
      conditions, the activation may involve a volume-dependent conformational change
      in the chloride channel.

PMID- 11226014
TI  - The effect of food restriction on morphological and metabolic development in two
      lines of growing Japanese quail chicks.
AB  - To investigate whether there is a relationship between the inherent maximum
      growth rate of a chick and its degree of developmental plasticity, we studied the
      effects of food restriction on morphological and physiological development in P
      line (selected for high growth rates) and C-line (nonselected) chicks of the
      Japanese quail between 2 and 64 d of age. In each line, three groups were
      created; one group in which the chicks were fed ad lib. and two other groups in
      which the chicks received 70% and 40% of the line-specific ad lib. feeding
      levels, respectively. In all three groups, chick survival rates were very high,
      and no relationship was detected between feeding level and chick mortality. The
      experimental feeding levels strongly affected the chicks' attainment of body mass
      at all ages. In addition, at most ages the growth of the structural components
      (wing, tarsus, and head) were also significantly affected by the feeding
      experiment but to a much smaller extent than the body mass. The feeding levels
      also affected the achievement of female sexual maturity such that, at the end of
      the experiment, most of the ad lib.-fed females and none of the females that
      received 40% of the ad lib. feeding level were laying eggs. In chicks of both
      lines that were fed ad lib., homeothermy was achieved at 7 d of age, but in
      chicks that received 40% of the line-specific ad lib. levels, homeothermy was
      achieved after 15-22 d of age. Poikilothermic chicks (P- and C-line) that were
      relatively heavy for their age exhibited relatively high resting metabolic rates
      (RMRs) and peak metabolic rates (PMRs) for their age. In addition, a positive
      relationship was found between the chicks' relative mass and RMR (based on mass
      based predictive equations). No relationship was detected between the chicks'
      relative body mass and their relative PMR (relative to mass-based predictive
      equations). With respect to the metabolic scope (i.e., PMR-RMR), Japanese quail
      chicks exhibited remarkable developmental plasticity: chicks with body masses
      that were 50% lower than the normal growing chicks did exhibit a normal capacity
      of thermogenic heat production for their mass. Because no differences were found
      with respect to the level of plasticity of morphological and physiological
      development between the two strains, we conclude that the selection for high
      postnatal growth rates in P-strain chicks has not resulted in a in a higher
      vulnerability of these chicks to food restrictions.

PMID- 11226016
TI  - Scaling of respiratory variables and the breathing pattern in birds: an
      allometric and phylogenetic approach.
AB  - Allometric equations can be useful in comparative physiology in a number of ways,
      not the least of which include assessing whether a particular species deviates
      from the norm for its size and phylogenetic group with respect to some specific
      physiological process or determining how differences in design among groups may
      be reflected in differences in function. The allometric equations for respiratory
      variables in birds were developed 30 yr ago by Lasiewski and Calder and presented
      as "preliminary" because they were based on a small number of species. With the
      expanded data base now available to reconstruct these allometries and the call
      for taking account of the nonindependence of species in this process through a
      phylogenetically independent contrasts (PIC) approach, we have developed new
      allometric equations for respiratory variables in birds using both the
      traditional and PIC approaches. On the whole, the new equations agree with the
      old ones with only minor changes in the coefficients, and the primary difference
      between the traditional and PIC approaches is in the broader confidence intervals
      given by the latter. We confirm the lower VE/VO2 ratio for birds compared to
      mammals and observe a common scaling of inspiratory flow and oxygen consumption
      for birds as has been reported for mammals. Use of allometrics and comparisons
      among avian groups are also discussed.

PMID- 11226015
TI  - Thermal acclimation, growth, and burst swimming of threespine stickleback:
      enzymatic correlates and influence of photoperiod.
AB  - Threespine sticklebacks (Gasterosteus aculeatus) that had been reared in the
      laboratory under natural photoperiods were acclimated to 23 degrees and 8 degrees
      C in late spring under increasing day lengths and again in late fall under
      decreasing day lengths. The parents of these fish were from the anadromous Isle
      Verte population. In the spring, cold- and warm-acclimated fish grew at the same
      rates and attained similar condition factors (mass L(-3)), although food intake
      was considerably higher at 23 degrees C. As both groups had similar increases in
      mass and condition, the higher axial muscle activities of citrate synthase and
      phosphofructokinase (measured at 20 degrees C) after cold acclimation were likely
      a direct response to temperature. Multiple regression analysis showed that axial
      muscle levels of cytochrome C oxidase and citrate synthase were correlated with
      the burst swimming speeds of the spring sticklebacks, while growth rates were
      positively correlated with lactate dehydrogenase levels in pectoral and axial
      muscles and creatine kinase levels in the axial muscle. In the fall, the fish in
      both acclimation groups grew little, although they fed at similar rates as in the
      spring experiment. Overall, the sticklebacks showed lower burst swimming speeds
      in the fall. In both spring and fall, the burst speeds of cold- and warm
      acclimated sticklebacks only differed at warm temperatures. In the spring
      experiment, the cold-acclimated fish swam faster, whereas in the fall experiment
      the warm-acclimated fish swam faster despite their lower percentage of axial
      muscle. Swimming speeds were measured both at a fish's acclimation temperature
      and after 12 h at the other temperature. Cold-acclimated sticklebacks seem to
      have more facility in rapidly adjusting to warm temperatures when they have
      experienced increasing rather than decreasing day lengths, perhaps as a result of
      the requirements of the spring migration to the intertidal breeding grounds.

PMID- 11226017
TI  - Postexercise ketosis in night-migrating passerine birds.
AB  - This study investigated the postexercise metabolism of six species of free
      living, night-migrating passerine birds (European robin, pied flycatcher,
      wheatear, redstart, blackcap, and garden warbler). The birds were caught during
      autumn migration out of their nocturnal flight, and their metabolism changed from
      a fasting, highly active state to a fasting, resting state. Concentrations of six
      plasma metabolites of the fat, carbohydrate, and protein metabolism were measured
      during up to 10 h of recovery time. The metabolic changes indicated a biphasic
      pattern: (a) a quick first response to the reduced energy demands during the
      first 20 min of recovery, suggested by an increase and subsequent decrease of
      free fatty acid levels, and (b) subsequently, a postexercise ketosis and a
      reduction of lipolysis and proteolysis, suggested by high beta-hydroxy-butyrate
      and low free fatty acid, glycerol, triglyceride, and uric acid levels. This
      metabolic pattern differs from that of humans and rats, in which ketosis starts
      immediately postexercise or is absent in trained subjects. Since migrating birds
      are naturally adapted to endurance exercise, it is hypothesized that the high and
      long-lasting postexercise ketosis does not evoke physiological problems (such as
      hypoglycemia) but, by contrast, increases the ability of birds to rely on lipids,
      to a very high extent, during and after flight and decreases the dependence on
      glucose and glucogenic amino acids. Differences between species in fat stores and
      metabolic pattern support this hypothesis.

PMID- 11226018
TI  - Effects of walking on ventilatory and cardiac function in intact and cardiac
      impaired lobsters.
AB  - Decapod crustaceans with normal heart function respond to the increased oxygen
      delivery requirements during walking with a step increase in heart and
      ventilation rate. In American lobsters, ventilation rate increased by the same
      amount during exercise at two walking speeds (2.4 and 8 m min(-1)); however,
      ventilation volume was significantly greater at the fastest walking speed (280 mL
      min(-1)) compared to animals at rest or walking at the slower speed (180 mL min(
      1)). The heart responded in a similar manner to locomotion. Heart rate was
      elevated to the same level at the two different walking speeds, but cardiac
      stroke volume was greater, implying increased cardiac output, at the faster
      walking speed. The communication and compensation between the cardiac and
      ventilatory systems was revealed when the function of one was impaired.
      Ventilatory rate was significantly elevated when cardiac output was impaired by
      sectioning two of the alary ligaments and/or the regulatory nerves to the heart.
      When cardiac output was more severely impaired, ventilation rate was greater.
      Despite ventilatory compensation, anaerobic metabolism made a greater
      contribution to energy production with impaired heart function. Hemolymph lactate
      concentration was three to five times greater in impaired animals than controls.
      It is known that the ventilatory and cardiac systems of lobsters are coregulated.
      These data demonstrate that the performance of one system can respond to
      compensate for impaired function in the other.

PMID- 11226019
TI  - Morphology and function of gill mitochondria-rich cells in fish acclimated to
      different environments.
AB  - The objective of this study is to test the hypothesis that morphologically
      different mitochondria-rich (MR) cells may be responsible for the uptake of
      different ions in freshwater-adapted fish. Tilapia (Oreochromis mossambicus) were
      acclimated to high-Ca, mid-Ca, low-Ca, and low-NaCl artificial freshwater,
      respectively, for 2 wk. Cell densities of wavy-convex, shallow-basin, and deep
      hole types of gill MR cells as well as whole-body Ca(2+), Na(+), and Cl(-)
      influxes were measured. Low-Ca fish developed more shallow-basin MR cells in the
      gills and a higher Ca(2+) influx than those acclimated to other media. However,
      fish acclimated to low-NaCl artificial freshwater predominantly developed wavy
      convex cells, and this was accompanied by the highest Na(+) and Cl(-) influxes.
      Relative abundance of shallow-basin and wavy-convex MR cells appear to be
      associated with changes in Ca(2+) and Na(+)/Cl(-) influxes, suggesting that
      shallow-basin and wavy-convex MR cells are mainly responsible for the uptake of
      Ca(2+) and Na(+)/Cl(-), respectively.

PMID- 11226020
TI  - Vasoactive receptors in abdominal blood vessels of the dogfish shark, Squalus
      acanthias.
AB  - Previous studies have demonstrated that the ventral aorta of the dogfish shark,
      Squalus acanthias, responds to a variety of cell-signaling agents. To investigate
      the generality of vasoactive receptors in the shark vasculature, in particular a
      conductance artery (anterior mesenteric) and vein (posterior intestinal), I
      measured the effect of acetylcholine, endothelin, nitric oxide, natriuretic
      peptides, and prostaglandins on tension in isolated rings from these vessels.
      Both vessels responded to these agents, and responses to receptor-specific
      ligands for endothelin and natriuretic peptide receptors suggest that B-type
      endothelin receptors are expressed in both vessels and that the artery expresses
      both A- and B-type natriuretic peptide receptors; however, the vein (like the
      ventral aorta) expresses only the B-type natriuretic peptide receptor. My data
      suggest that a suite of signaling systems is ubiquitous in both arteries and
      veins in at least this elasmobranch species. Their role in hemodynamics and
      osmoregulation (perfusion of gill and rectal gland) remains to be determined.

PMID- 11226021
TI  - Evidence of nitric oxide and angiotensin II regulation of circulation and
      cutaneous drinking in Bufo marinus.
AB  - The nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (l-NAME)
      increased vascular resistance (VR) 10% above baseline of 3.08+/-0.08 (n=11)
      mmHg/mL/min at 10 mg/kg and 20% above 3.05+/-0.08 (n=9) at 50 mg/kg in
      anesthetized toads (Bufo marinus). Blood pressure was unaffected by either dose
      of L-NAME. Blood flow decreased at the higher dose of L-NAME. L-arginine (300
      mg/kg) reversed the effects of L-NAME on VR and blood flow in toads treated with
      10 mg/kg but not with 50 mg/kg. Injection of 50 mg/kg L-NAME into empty-bladder
      toads produced a 10% decrease in water uptake, J(v), resulting in a J(v) of
      1,267+/-11 cm(3)/cm(2)/s x 10(-7) (n=9) compared to 1,385+/-12 (n=8) for
      controls. Injection of 10 microg/kg angiotensin II (ANG II) increased J(v) 15%
      across the pelvic patch (J(v), cm(3)/cm(2)/s x 10(-7)), resulting in a J(v) of
      1,723+/-12 cm(3)/cm(2)/s x 10(-7) (n=8) compared to 1,471+/-12 (n=8) for
      controls. It is hypothesized that during cutaneous drinking blood flow into the
      capillary bed of the pelvic patch is regulated by nitric oxide and ANG II.

PMID- 11226023
TI  - Mass-specific and whole-animal metabolism are not the same concept.

PMID- 11226022
TI  - Interspecific and intraspecific variation in proximate, mineral, and fatty acid
      composition of milk in Old World fruit bats (Chiroptera: Pteropodidae).
AB  - We examine the effect of body mass on milk composition among Old World fruit
      bats, including Pteropus pumilus (0.175 kg), Pteropus rodricensus (0.265 kg),
      Pteropus hypomelanus (0.571 kg), and Pteropus vampyrus (1.133 kg). We describe
      intra- and interspecific differences in the proximate composition of milk among
      these four species and the minerals and fatty acids in the milk of the latter two
      species. There were no differences between species in the concentrations of dry
      matter, fat, or lactose in milk. However, there were significant, although small,
      differences in the protein content of milk among species, with protein being
      significantly greater in P. rodricensus than in P. pumilus and P. hypomelanus and
      protein being significantly less in P. hypomelanus than in P. rodricensus and P.
      vampyrus. There were no differences in mineral content between P. hypomelanus and
      P. vampyrus in milk minerals, but minor differences were evident in fatty acids
      12:0, 14:0, 18:0, 18:1n11, and 18:2n6. Our findings suggest that milk composition
      is relatively constant across lactation for most proximate, mineral, and fatty
      acid components. We found a significant increase in dry matter and energy across
      lactation in the concentration of dry matter and energy in P. pumilus and fat in
      P. hypomelanus. In P. hypomelanus, we found a significant increase in the
      concentration of fatty acids 10:0 and 20:1n9 and a significant decrease in Iso15
      and 20:1n7. No other differences associated with day of lactation were found.
      These findings suggest that milk composition is generally similar within the
      genus Pteropus, despite a 6.5-fold difference in body mass between species that
      we evaluated.

PMID- 11226025
TI  - Cytokine control in human endometrium.
AB  - Cytokines within endometrium participate in both menstruation and implantation
      but also contribute to the defence mechanisms of the mucosal epithelium.
      Endometrium is under the control of steroid hormones, particularly progesterone
      and, thus, control of cytokines by this steroid is important. Although
      appreciable numbers of progesterone receptors are not found in endometrial
      leucocytes, progesterone can modulate cytokines by acting on uterine cells
      expressing the receptor. The NFkappaB pathway is important in the control of
      cytokine synthesis and can modulate production of chemokines, matrix
      metalloproteinases and the inducible prostaglandin synthesis enzyme COX-2.
      NFkappaB activity can be inhibited by progesterone by either stimulating
      synthesis of IkappaB, the molecule that restrains NFkappaB in the cytosol, or
      after binding to the nuclear receptor, competing with NFkappaB for recognition
      sites on the relevant gene. In this way, progesterone can limit pro-inflammatory
      pathways. The major palliatives for endometrial dysfunctions such as menorrhagia
      and dysmenorrhoea have been the non-steroidal anti-inflammatory drugs that
      inhibit prostaglandin synthesis. Prostaglandins have major effects on cytokine
      production but the direct action of prostaglandin E on leucocytes is not a pro
      inflammatory response but is to stimulate interleukin 10 and inhibit interleukin
      12 synthesis. The likely effect of the non-steroidal anti-inflammatory drugs is
      on the cells surrounding the small blood vessels, where a synergistic action
      between prostaglandin and chemokine will induce leucocyte entry and activation
      leading to lysis of connective tissue and menstruation. At the time of
      implantation, tight control of cytokine synthesis is required. Although leukaemia
      inhibitory factor is essential to implantation, the mouse knockout models show
      that the prostaglandin system is also essential but that there are mutually
      supportive pathways that compensate for the knockout of many cytokines.

PMID- 11226026
TI  - Is there an FSH-releasing factor?
AB  - A thorough understanding of the factors that regulate the secretion of FSH is
      critical for the development of efficient methods for fertility regulation. The
      purpose of this review is to evaluate what is currently known about the existence
      of FSH-releasing factor(s). It considers the obstacles encountered in
      understanding the control of FSH secretion, current knowledge of the nature of
      FSH secretion and the mechanisms involved in controlling FSH secretion, the
      arguments that have been posed against the need for an FSH-releasing factor and
      finally the evidence available to date supporting the existence of FSH-releasing
      factor(s).

PMID- 11226027
TI  - DNA repair mechanisms and gametogenesis.
AB  - In mammals, there is a complex and intriguing relationship between DNA repair and
      gametogenesis. DNA repair mechanisms are involved not only in the repair of
      different types of DNA damage in developing germline cells, but also take part in
      the meiotic recombination process. Furthermore, the DNA repair mechanisms should
      tolerate mutations occurring during gametogenesis, to a limited extent. In the
      present review, several gametogenic aspects of DNA mismatch repair, homologous
      recombination repair and postreplication repair are discussed. In addition, the
      role of DNA damage-induced cell cycle checkpoint control is considered briefly.
      It appears that many genes encoding proteins that take part in DNA repair
      mechanisms show enhanced or specialized expression during mammalian
      gametogenesis, and several gene knockout mouse models show male or female
      infertility. On the basis of such knowledge and models, future experiments may
      provide more information about the precise relationship between DNA repair,
      chromatin dynamics, and genomic stability versus instability during
      gametogenesis.

PMID- 11226028
TI  - Trophoblast interferon and pregnancy.
AB  - The maternal recognition of pregnancy in ruminants requires the production of
      interferons by the preimplantation blastocyst. These proteins, the trophoblast
      interferons (IFN-tau), are the products of a number of similar genes, the
      expression of which is controlled by characteristic promoter regions. They are
      expressed for a short period in high concentrations, and have antiluteolytic,
      antiviral, antiproliferative and immunomodulatory effects, through receptors on
      the endometrial epithelium. The antiluteolytic effects of IFN-tau result from
      inhibition of endometrial expression of the oxytocin receptor, through which
      circulating oxytocin stimulates episodic prostaglandin F2a production. Some of
      the properties of IFN-tau differ from those of other type I interferons, and they
      may have novel therapeutic effects. Because of their central role in early
      gestation, these proteins have excited the interest of reproductive
      physiologists. However, their other properties, and the fact that their
      expression is controlled so precisely, have made them of interest to a wide range
      of biologists.

PMID- 11226029
TI  - Maturation of human oocytes in vitro and their developmental competence.
AB  - Complete maturation of oocytes is essential for the developmental competence of
      embryos. Any interventions in the growth phase of the oocyte and the follicle in
      the ovary will affect oocyte maturation, fertilization and subsequent embryo
      development. Oocyte size is associated with maturation and embryo development in
      most species examined and this may indicate that a certain size is necessary to
      initiate the molecular cascade of normal nuclear and cytoplasmic maturation. The
      minimum size of follicle required for developmental competence in humans is 5-7
      mm in diameter. Maturation in vitro can be accomplished in humans, but is
      associated with a loss of developmental competence unless the oocyte is near
      completion of its preovulatory growth phase. This loss of developmental
      competence is associated with the absence of specific proteins in oocytes
      cultured to metaphase II in vitro. The composition of culture medium used
      successfully for maturation of human oocytes is surprisingly similar to that
      originally developed for maturation of oocytes in follicle culture in vitro. The
      presence of follicle support cells in culture is necessary for the gonadotrophin
      mediated response required to mature oocytes in vitro. Gonadotrophin
      concentration and the sequence of FSH and FSH-LH exposure may be important for
      human oocytes, particularly those not exposed to the gonadotrophin surge in vivo.
      More research is needed to describe the molecular and cellular events, the
      presence of checkpoints and the role of gene expression, translation and protein
      uptake on completing oocyte maturation in vitro and in vivo. In the meantime,
      there are very clear applications for maturing oocytes in human reproductive
      medicine and the success rates achieved in some of these special applications are
      clinically valuable.

PMID- 11226030
TI  - Stage-specific and differential expression of gap junctions in the mouse ovary:
      connexin-specific roles in follicular regulation.
AB  - Gap junction communication plays an essential role in follicle growth.
      Immunocytochemistry and confocal microscopy were used to examine the expression
      of gap junction connexins of the alpha and beta subfamilies in follicles from
      primordial to preovulatory stages in the ovaries of prepubertal and adult mice.
      Connexin-specific antibodies detected alpha(1), alpha(4), alpha(6), beta(1),
      beta(2) and beta(4) connexins within follicles. In adult ovaries connexin
      immunolabelling was stronger in larger (more mature) follicles than it was in
      smaller follicles, with comparatively reduced labelling detected in prepubertal
      ovaries. In healthy follicles, labelling for alpha subfamily connexins was
      detected between granulosa cells, whereas labelling for beta subfamily connexins
      was found in the theca. Labelling for beta subfamily connexins and alpha(4)
      connexin (preantral stage) was detected on the oocyte surface membrane. In
      atretic follicles, labelling for beta(4) connexin appeared between the granulosa
      cells. These results demonstrate that alpha and beta connexin subfamilies are
      segregated to separate cellular compartments in the mouse follicle. The results
      are discussed in the light of possible roles for differential gap junctional
      communication in the regulation of folliculogenesis, oocyte maturation and
      atresia.

PMID- 11226032
TI  - Induction of final maturation by sperm penetration in canine oocytes.
AB  - In contrast to oocytes of most mammals, the canine oocyte is at the germinal
      vesicle stage at ovulation. Moreover, the bitch is receptive to mating while
      immature oocytes are present in the oviducts. The aims of this study were to
      examine the influence of fertilization in immature oocytes on the resumption of
      meiosis, and the modification of both male and female chromatin in fertilized
      oocytes. Canine cumulus-oocyte complexes collected from routine ovariectomies
      were cultured in medium 199 with 20% fetal calf serum for 24 h, incubated in the
      same medium with fresh semen for 24 h, washed, cultured for a further 24 h and
      fixed. Control oocytes were cultured in the same medium but without spermatozoa
      for 24, 48 or 72 h. After fixation, chromatin was stained with propidium iodide
      and examined using laser scanning confocal microscopy. The data indicate that
      sperm penetration can occur in immature canine oocytes and that it induces
      resumption of meiosis. After 72 h of culture, the percentage of oocytes at the
      germinal vesicle stage was significantly lower in fertilized oocytes (40% versus
      60.3% for control oocytes; P < 0.05) and the percentage of oocytes beyond
      metaphase I was significantly greater in fertilized oocytes (28.3% metaphase I
      and II, and two pronuclei versus 10.2% metaphase I and II for control oocytes; P
      < 0.01). Observation and measurement of the area of chromatin in fertilized
      oocytes showed an overall parallel condensation-decondensation of both female and
      male chromatin from the germinal vesicle stage to the pronuclear stage.

PMID- 11226031
TI  - Role of ascorbic acid in promoting follicle integrity and survival in intact
      mouse ovarian follicles in vitro.
AB  - Ascorbic acid has three known functions: it is necessary for collagen synthesis,
      promotes steroidogenesis and acts as an antioxidant. Within the ovary, most
      studies have concentrated on the role of ascorbic acid in luteal formation and
      regression and little is known about the function of this vitamin in follicular
      growth and development. Follicular growth and development were investigated in
      this study using an individual follicle culture system that allows the growth of
      follicles from the late preantral stage to Graafian morphology. Follicles were
      isolated from prepubertal mice and cultured for 6 days. Control media contained
      serum and human recombinant FSH. Further groups of follicles were cultured in the
      same media but with the addition of ascorbic acid at concentrations of either 28
      or 280 micromol l(-1). Addition of ascorbic acid at the higher concentration
      significantly increased the percentage of follicles that maintained basement
      membrane integrity throughout culture (P < 0.001). Ascorbic acid had no effect on
      the growth of the follicles or on oestradiol production. Metalloproteinase 2
      activity tended to increase at the higher concentration of ascorbic acid and
      there was a significant concomitant increase in the activity of tissue inhibitor
      of metalloproteinase 1 (P < 0.01). Follicles cultured without the addition of
      serum but with FSH and selenium in the culture media underwent apoptosis.
      Addition of ascorbic acid to follicles cultured under serum-free conditions
      significantly reduced apoptosis (P < 0.05). From these data it is concluded that
      ascorbic acid is necessary for remodelling the basement membrane during
      follicular growth and that the ability of follicles to uptake ascorbic acid
      confers an advantage in terms of granulosa cell survival.

PMID- 11226033
TI  - Development of cultured bovine embryos after exposure to high temperatures in the
      physiological range.
AB  - Embryonic development is inhibited by exposure of cultured embryos to high
      temperatures. However, culture temperatures used to demonstrate the effects of
      heat on development have been higher than the body temperatures experienced
      typically by heat-stressed cows. The aim of this study was to determine whether
      exposing bovine oocytes and embryos to temperatures characteristic of body
      temperatures of heat-stressed cows would affect embryonic development in vitro.
      The CO2 percentage of the gas phase was adjusted in all experiments to prevent pH
      changes in the medium caused by decreased solubility of CO2 at high temperatures.
      Fertilization of oocytes at 41.0 degrees C reduced cleavage rate and the
      percentage of oocytes that became blastocysts compared with at 38.5 degrees C.
      There was no deleterious effect of fertilization at 40.0 degrees C. When putative
      zygotes and two-cell embryos were exposed to a range of temperatures from 38.5 to
      41.0 degrees C for 3, 6, 9 or 12 h, heat shock reduced the number that developed
      to the blastocyst stage but only after exposure to 41.0 degrees C for 9 or 12 h.
      In addition, it was tested whether low O2 tension would reduce the detrimental
      effects of heat shock. The deleterious effect of 41.0 degrees C was not dependent
      upon oxygen content or the gas mixture used for culture (5% versus 20.95% O2),
      indicating that the deleterious effects of heat shock did not depend upon a high
      O2 environment. In the final experiment, embryos were exposed to 24 h
      fluctuations in temperature designed to mimic the rectal temperatures of cows
      exposed to heat stress. Exposure of embryos to this pattern of temperatures
      starting after fertilization reduced development when embryos were exposed to
      this environment for 8 days but not when embryos were exposed for 1 day only.
      These findings indicate that embryonic development can be disrupted by a short
      term severe or a prolonged mild heat shock and that the effects of heat shock are
      not artefacts of changes in pH or high oxygen tension.

PMID- 11226035
TI  - Effect of gonadotrophins on the ovarian interstitial tissue of the wood mouse,
      Apodemus sylvaticus.
AB  - The ovarian interstitial tissue of the wood mouse (Apodemus sylvaticus) is
      extensively developed. The effect of equine chorionic gonadotrophin (eCG) and
      human chorionic gonadotrophin (hCG) on ovarian interstitial tissue was
      investigated in wood mice from a laboratory stock. The tissue was assessed by
      measuring the relative size of the cells, cell nucleus diameter and (in adults)
      nuclear shape. Hormone-treated wood mice had larger interstitial cells and larger
      cell nuclei than untreated animals. In addition, the cell nuclei of adult hormone
      treated wood mice had a smooth round or oval outline, whereas those of untreated
      animals had an irregular outline with spiky projections. Electron microscopy
      showed that the irregular spiky outline of the cell nuclei in untreated wood mice
      was caused by distortions of the nuclear membrane by a large number of
      intracellular lipid droplets; the droplets were less abundant in the hormone
      treated animals. These experiments indicate that the cells of the interstitial
      tissue of the wood mouse are under the control of gonadotrophins, and that these
      cells are likely to be a site of the synthesis and release of steroid hormones.
      The methods used in this study to assess the state of the cells could be applied
      to animals from the field to investigate the role of interstitial tissue in the
      reproductive biology of wood mice.

PMID- 11226034
TI  - Ovarian autoimmunity in relation to egg production in laying hens.
AB  - The aim of this study was to determine whether anti-ovarian autoantibodies appear
      in the circulation of laying hens and whether the concentrations of these
      antibodies change with respect to ageing and egg laying rate. Autoantibodies to
      ovarian tissues in the circulation of aged (aged approximately 670 days) White
      Leghorn hens with low (< 50%) and high (> 90%) egg laying rates were examined by
      ELISA and western blotting. Young laying hens (aged 185 days) with > 95% egg
      production were used as controls. The results of the ELISA indicated that IgG,
      which bound to the ovary and small white follicles, was present in the
      circulation of old laying hens. More hens that laid few eggs had circulatory
      autoantibodies to the ovary and small white follicles, as determined by the cut
      off value in ELISA (mean absorbance + 2 SD of young laying hens), than did hens
      that laid greater numbers of eggs, and the concentration of IgG was significantly
      higher in the hens that laid few eggs. In contrast, when the muscle proteins were
      used as antigens there were no significant differences in the absorbance values
      among low and high laying frequency old hens or young hens. Western blotting
      revealed many bands of immunoprecipitates formed by ovarian antigens and
      antibodies in the serum of old hens, indicating the presence of many binding
      sites for circulatory IgG in ovarian tissues. These results indicate that
      antibodies to ovarian tissues appear in the circulation of laying hens during
      ageing, and that the concentration of these autoantibodies is related inversely
      to the rate of egg laying by hens.

PMID- 11226036
TI  - Inhibition of human and ovine acrosomal enzymes by tannic acid in vitro.
AB  - The effect of tannic acid, a common flavonoid, on the acrosin and plasminogen
      activator activity and plasmin activity of human and ram spermatozoa was
      evaluated. Acrosin and plasminogen activator activity were determined by
      spectrophotometry using the chromogenic substrates N-alpha-benzoyl-DL-arginine
      para-nitroanilide-HCl (BAPNA) and H-D-valyl-L-leucyl-L-lysine-p-nitroanilide-2HCl
      (S-2251), respectively. In extracts from both human and ovine acrosomes, the
      activities of acrosin and plasminogen activators were susceptible to tannic acid
      inhibition. The inhibitory effect of tannic acid was observed at concentrations >
      50 micromol l(-1) in a dose-dependent manner. In additional experiments, low
      concentrations of tannic acid significantly inhibited tissue-type plasminogen
      activator, urokinase-type plasminogen activator and plasmin activity in a
      concentration-dependent manner over the range 0.25-200 micromol l(-1). Tannic
      acid reduced the motility of ram spermatozoa at a concentration of 1000 micromol
      l(-1) after 2 and 3 h co-incubation with spermatozoa. The motility of human
      spermatozoa remained unchanged over the range 0.1-1000 micromol tannic acid l(-1)
      during 3 h co-incubation. These results indicate that tannic acid inhibited the
      activity of both acrosin and plasminogen activator and indicates a possible
      mechanism by which flavonoids exert their antifertility effects.

PMID- 11226037
TI  - Ultrasound and endocrine evaluation of the ovarian cycle and early pregnancy in
      the Sumatran rhinoceros, Dicerorhinus sumatrensis.
AB  - Longitudinal ultrasound and endocrine evaluations were conducted in two adult
      female Sumatran rhinoceroses (Dicerorhinus sumatrensis) over a period of 12-22
      months to learn more about their reproductive physiology. Rectal ultrasonography
      was conducted to monitor ovarian activity. Blood samples were collected and
      analysed for progesterone and LH, and faecal samples were analysed for progestin
      metabolites. One female showed cyclic ovarian activity during the study period,
      whereas the other female showed no evidence of ovarian activity. The cyclic
      Sumatran rhinoceros appeared to be an induced ovulator, the first of its kind
      reported within the Perrisodactyla. Ultrasound examinations of the ovaries
      revealed the formation of anovulatory haemorrhagic follicles when the animal was
      not mated. These follicles appeared to undergo varied degrees of luteinization
      that resulted in irregular faecal progestin profiles. When allowed to mate, the
      female showed a 21 day reproductive cycle that was reflected in both faecal
      progestin and serum progesterone profiles. The concentration of serum LH was
      baseline before mating, increased approximately 30-fold within 1-2 h of
      intromission and returned to baseline within 22 h. Ovulation occurred within 46 h
      of copulation. The female conceived three times during the study. Pregnancy was
      detected using ultrasonography 14-16 days after mating, and the concentration of
      both serum progesterone and faecal progestins remained high. Early embryogenesis
      appeared to be similar to that in horses. However, each pregnancy terminated
      unexpectedly within the first 3 months of gestation. This study demonstrates the
      important role that basic research and reproductive technology can play in
      developing a natural breeding programme for an endangered animal in captivity.

PMID- 11226038
TI  - Effect of a single dose of ibuprofen lysinate before embryo transfer on pregnancy
      rates in cows.
AB  - Embryo implantation is a critical step in both cows and humans. The use of
      ibuprofen lysinate to enhance implantation has been investigated in cattle with
      the specific aim of improving pregnancy rates after embryo transfer. In this
      study, heifers (n = 100) were assigned randomly to one of two groups: one group
      was treated i.m. with 5 mg ibuprofen lysinate kg(-1) body weight 1 h before
      embryo transfer and a control group received vehicle only. A single embryo was
      transferred into each recipient cow. There was a significant difference in the
      number of pregnancies after embryo transfer between cows in the treated (41 of
      50; 82%) and control (28 of 50; 56%) groups (P < 0.05). These data indicate that
      ibuprofen lysinate may be an effective adjunctive treatment for assisted
      reproduction in cattle. Further studies are needed to clarify whether this effect
      is associated with the reduction of cyclooxygenase enzyme isoforms during embryo
      transfer or whether other mechanisms are involved.

PMID- 11226039
TI  - Anatomical and histological changes in the oviducts of Japanese quail, Coturnix
      japonica, after embryonic exposure to ethynyloestradiol.
AB  - Oestrogen is needed for normal oviductal development in female birds, but
      excessive early exposure to oestrogen can cause oviductal abnormalities and
      impair egg-laying ability. In this study, the anatomical and histological effects
      of in ovo exposure to the synthetic oestrogen ethynyloestradiol on the oviducts
      of immature and adult female Japanese quail, Coturnix japonica, were
      investigated. A series of abnormalities was observed after injection of
      ethynyloestradiol (2 or 20 ng g(-1) egg) into the yolk on day 3 of incubation.
      Ethynyloestradiol induced precocious differentiation of the luminal epithelium
      and tubular glands in immature chicks. Right-side oviduct retention occurred at
      all the ages studied, whereas certain other effects were not evident until sexual
      maturity. The left oviduct was reduced in size and tubular gland density in the
      uterus (shell gland) was reduced in sexually mature birds that had been treated
      with ethynyloestradiol. The utero-vaginal junction was longer than in control
      birds and had a higher tubular gland density. The epithelial cells in the magnum
      were taller in birds treated with ethynyloestradiol. Embryonic exposure to the
      environmental contaminant ethynyloestradiol may cause persisting structural
      malformations in oviducts of quails, which can impair fertility. As oviductal
      malformations are indicative of embryonic exposure to exogenous oestrogen, they
      are potentially useful as biomarkers of xenooestrogen exposure in wild bird
      populations.

PMID- 11226040
TI  - Short-term storage of cane toad (Bufo marinus) gametes.
AB  - The responses of cane toad (Bufo marinus) gametes, used as a model for the
      development of assisted reproduction techniques for rare and endangered
      amphibians, to short-term storage at temperatures > 0 degrees C were studied.
      Whole excised testes were stored at 0 degrees or 4 degrees C for 15 days, and
      sperm motility was measured at excision and after storage for 2, 5, 7, 10, 12 and
      15 days. Spermatozoa showed > 50% motility for 7 days at 0 degrees C and for 5
      days at 4 degrees C. At 15 days, only spermatozoa stored at 0 degrees C still
      showed some motility (3%). Sperm suspensions were prepared at 5 day intervals
      over 30 days in simplified amphibian ringer (SAR) at dilutions of 1:1, 1:5 and
      1:10 (w/v) testes:SAR. Aliquots from each dilution were stored at 0 degrees C in
      Eppendorf tubes opened at 5 day intervals of storage (aerated) or kept sealed
      (unaerated) (treatments: aerated or unaerated; 5, 10, 15, 20, 25 and 30 days
      storage). After 30 days, sperm motility and fertilizing capacity were determined.
      The optimal protocol for sperm storage up to 10 days, as assessed by the
      retention of fertilizing capacity, was as a 1:5 testis:SAR (w/v) suspension,
      whereas the longest absolute retention of both motility and fertilizing capacity
      was observed in concentrated (1:1 dilution), anaerobic suspensions (up to 25-30
      days). Oviductal oocytes placed in SAR at 5, 10, 15, 20 and 25 degrees C
      immediately after ovulation lost viability when cooled rapidly to 5 degrees C and
      stored for 2 h. However, oocytes retained viability for up to 8 h at the optimum
      storage temperature of 15 degrees C. Thus, it is concluded that during short-term
      storage spermatozoa retain viability for longer than oocytes, and that
      spermatozoa in suspensions retain viability for longer than spermatozoa stored in
      situ in excised testes.

PMID- 11226041
TI  - Relationship between maternal endocrine environment, early embryo development and
      inhibition of the luteolytic mechanism in cows.
AB  - In this study, the relationship between maternal hormone environment and early
      embryo development in mature non-lactating Holstein-Friesian cows was
      investigated. Animals were inseminated at either 72 or 96 h after prostaglandin
      injection (n = 23) or were left as uninseminated controls (n = 10). Plasma
      samples were collected once a day from the first day of insemination (day 1)
      until day 16, when the cows underwent an oxytocin challenge, and were then
      slaughtered and their reproductive tracts removed. The tracts were flushed to
      collect embryos and the flushes were measured for interferon tau (IFN-tau)
      activity. Inseminated cows without an embryo on day 16 (n = 5) underwent both
      delayed ovulation (indicated by delayed decrease in oestradiol concentrations)
      and a delayed increase in progesterone concentrations after ovulation compared
      with cows with an embryo on day 16 (n = 15). Within the group of cows with an
      embryo, those with poorly developed embryos producing undetectable concentrations
      of IFN-tau (n = 7) had similar oestradiol profiles but underwent a delayed
      progesterone increase after ovulation compared with cows with well developed
      embryos producing measurable quantities of IFN-tau (n = 8). In the cows with an
      embryo, the plasma concentration of 13,14-dihydro-15-keto PGF2a, the principal
      metabolite of PGF2a, after injection of oxytocin was lower than that of control
      cows and cows without an embryo. However, when the cows with an embryo were
      compared on the basis of production of embryonic IFN-tau, the PGF2a response to
      oxytocin was attenuated completely in cows that had measurable IFN-tau activity,
      whereas a response of similar magnitude to that in control cows and cows without
      an embryo was observed in those with undetectable IFN-tau activities. In
      conclusion, the successful maternal recognition of pregnancy in cows depends on
      the presence of a sufficiently well developed embryo producing sufficient
      quantities of IFN-tau, which is, in turn, dependent on an appropriate pattern of
      maternal progesterone secretion.

PMID- 11226042
TI  - Human endometrial angiogenesis.
AB  - Angiogenesis is the development of new microvessels from existing vessels, a
      process that involves microvascular endothelial cells. Physiological angiogenesis
      rarely occurs in adults except in the ovary and endometrium during the
      reproductive life of females. Angiogenesis occurs by sprouting and non-sprouting
      mechanisms. Since endothelial sprouts are not observed in human endometrium, we
      hypothesized that non-sprouting mechanisms such as intussusception and elongation
      are involved in endometrial angiogenesis. The demand for angiogenesis differs
      spatially and temporally in the endometrium: angiogenesis occurs in the basalis
      layer during menstruation and in the functionalis and subepithelial capillary
      plexus during the proliferative and early secretory stages. Most studies have
      failed to demonstrate a link between expression of endometrial angiogenic factors
      and new vessel growth. However, we demonstrated recently a strong relationship
      between vascular endothelial growth factor (VEGF) immunolocalized in in
      travascular neutrophils and endothelial cell proliferation in each of the
      subepithelial capillary plexus, functionalis and basalis regions of the human
      endometrium. Our data also indicate that focal neutrophil VEGF has a role in the
      development of the subepithelial capillary plexus and functionalis microvessels
      during the proliferative phase of the menstrual cycle. We propose that
      neutrophils are an intravascular source of VEGF for vessels that undergo
      angiogenesis by intussusception and elongation.

PMID- 11226043
TI  - Role of androgens and fibroblast growth factors in prostatic development.
AB  - This review focuses on the role of androgens and fibroblast growth factors (FGFs)
      in regulating the growth and development of the prostate. It is known that
      androgens and mesenchymal-epithelial interactions are required for the formation
      and growth of the prostate, but little is known of the molecular mediators
      regulating prostatic organogenesis. Paracrine signalling from the mesenchyme to
      the epithelium is a key element of prostatic development and the action of
      androgens in mesenchymal cells is essential for prostatic development. This
      finding has led to the hypothesis that androgens regulate the expression of
      paracrine-acting growth factors. Although several families of growth factors play
      a role in regulating prostatic growth, the FGF family contains members that have
      been studied most comprehensively in regard to prostatic growth and branching
      morphogenesis. The role of FGFs in prostatic development is described in detail,
      since two members of the FGF family function as mesenchymal paracrine-acting
      factors in the prostate. It has been shown that FGF7 and FGF10 play important
      roles during prostatic development yet they do not appear to be regulated
      directly by androgens. Current models propose that growth factor expression
      (including FGF7 and 10) is regulated directly by androgens. However, it is
      possible that androgen regulation is indirect and a model outlining indirect
      androgen regulation of growth factors is proposed.

PMID- 11226044
TI  - Potential roles of decidual prolactin in early pregnancy.
AB  - Successful establishment of pregnancy is dependent on uterine receptivity at the
      time of trophoblast invasion and implantation. The endometrium undergoes
      morphological and functional differentiation during the mid- to late secretory
      phase of the menstrual cycle in preparation for such an event. These changes are
      orchestrated by ovarian steroid hormones. However, local autocrine-paracrine
      signalling at the deciduo-placental interface is crucial for successful
      establishment of pregnancy. One key cytokine that may regulate many functions in
      implantation is prolactin. Prolactin is secreted by the decidualized endometrium
      at the time of predicted conception and, in the event of pregnancy, local
      expression and secretion of prolactin persists until term. Prolactin mediates its
      effect on target cells through interaction with single-pass transmembrane
      receptors. Localization of the sites of expression of the prolactin receptor
      indicates that the cytokine may regulate an array of functions in the pregnant
      uterus that are crucial in im-plantation and early pregnancy.

PMID- 11226045
TI  - Significance of incorporating measures of sperm production and function into rat
      toxicology studies.
AB  - The rat is the preferred species for reproductive toxicity testing. The inclusion
      of measures of rat sperm quality, such as motility and morphology, into
      reproductive test protocols often increases the sensitivity of the test to detect
      effects, and provides the toxicologist and risk assessor with valuable
      information about the nature of the reproductive toxicity of the test substance.
      Technical advances in computer-aided sperm analysis have made it possible to
      evaluate motion characteristics of rat spermatozoa. This technology can provide
      an objective means of classifying the motion of rat spermatozoa as progressive or
      non-progressive, as required in test protocols. More specific tests of rat sperm
      function are being applied for the purpose of evaluating modes and mechanisms of
      toxicant action. Computer-aided sperm analysis can be used to evaluate sperm
      motion during cultures that support sperm capacitation and to identify
      hyperactivated spermatozoa. Under the same culture conditions, acrosome-specific
      stains can be used to identify effects of toxicants on the acrosome reaction.
      These approaches, in combination with in vitro fertilization in rats, can
      pinpoint sperm functional deficits and thereby assist the toxicologist in
      addressing hypotheses regarding the cellular-molecular bases of toxicant-induced
      male infertility.

PMID- 11226046
TI  - Characterization of adenylyl cyclases in cultured human granulosa cells.
AB  - Granulosa cells play an essential role in follicular development and formation of
      corpora lutea. Many functions of granulosa-lutein cells are controlled by
      activation of G protein-coupled receptors and the formation of cyclic AMP (cAMP)
      by adenylyl cyclase. There are at least nine mammalian adenylyl cyclase
      isoenzymes, which show different sensitivities towards other signalling systems.
      The aim of this study was to identify the types of adenylyl cyclase present in
      human granulosa cells and to investigate its functional regulation by G proteins,
      calcium and the protein kinase C and A pathways. Granulosa cells were obtained
      from women undergoing IVF. The cells were maintained in primary culture and they
      consistently expressed mRNA coding for adenylyl cyclase I, III, VI, VII and IX.
      The signals for adenylyl cyclase V and VIII were more variable among patients and
      there was no signal for adenylyl cyclase II. The expression of multiple adenylyl
      cyclase proteins was confirmed by immunochemistry with subtype-specific
      antibodies. The formation of cAMP in cultured cells was stimulated many times by
      hCG (EC(50) value 4.2 iu ml(-1)) and by prostaglandin E(2) (PGE(2); EC(50) = 0.75
      micromol l(-1)) in a concentration-dependent manner, thus confirming the presence
      of receptors coupled positively to G(s). The diterpene forskolin, which
      stimulates all isoforms of adenylyl cyclase except for adenylyl cyclase IX,
      increased cAMP formation to higher levels than hCG or PGE(2). The strong
      stimulation by forskolin indicates that adenylyl cyclase IX is unlikely to be the
      major source of cyclase activity in these cells. Basal and forskolin- or PGE(2)
      stimulated adenylyl cyclase activity was amplified 1.5-2.0 times by phorbol-12,13
      dibutyrate, indicating that protein kinase C-sensitive enzymes (for example,
      adenylyl cyclase types IV, V, VI or VII) may be active in the cells. In contrast,
      hCG-stimulated activity was inhibited (76 +/- 6%) by phorbol ester. Stimulation
      of G(i) with the alpha-adrenoceptor agonist clonidine inhibited hCG-induced
      cyclase activity. This finding indicates that adenylyl cyclase II and IV
      subtypes, which are stimulated by betagamma subunits released from G(i), are not
      predominant. Increases in intracellular free calcium concentrations by the
      ionophore A23187, the calcium-ATPase inhibitor thapsigargin or by fluprostenol, a
      selective prostanoid FP receptor agonist, which is known to open calcium channels
      in granulosa cells, or removal of calcium by EGTA, had no significant effects on
      basal or forskolin-stimulated formation of cAMP. These results indicate that
      subtypes adenylyl cyclase I, III and VIII, which are activated by calcium, and
      adenylyl cyclase V and VI, which are inhibited by calcium, are not dominant
      isoforms in granulosa-lutein cells. The protein kinase A inhibitor H89 had no
      effects on formation of cAMP; this finding rules out the involvement of adenylyl
      cyclase V and VI subtypes, which are subjected to negative feedback by protein
      kinase A. These results indicate that adenylyl cyclase VII is the dominant
      functional isoenzyme in human granulosa-lutein cells.

PMID- 11226047
TI  - Alterations in ovarian function of mice with reduced amounts of KIT receptor.
AB  - The KIT receptor, present on oocyte and theca cells in ovarian follicles, and its
      ligand, KIT LIGAND, produced by granulosa cells, are encoded at the Kit gene and
      the Mgf gene, respectively. Both Kit and Mgf mutations affect oogenesis and
      folliculogenesis. In this study, the ovarian function of heterozygous mice with a
      mutation Kit(W-lacZ) was examined. Firstly, the amounts of KIT and KIT LIGAND
      proteins in the ovaries of mice at different ages were determined. Secondly, in
      vivo and in vitro folliculogenesis of wild type and heterozygous mice were
      compared. Western blotting showed that the amounts of both KIT and KIT LIGAND
      proteins were decreased in mutant mice. Ovarian follicle populations were counted
      and more type 5a follicles and fewer type 5b (preantral follicles) were present
      in ovaries from Kit(W-lacZ/+) ovaries. Furthermore, the relationships between
      oocyte size and follicle size differed between wild type and heterozygous mice.
      This finding may be a consequence of altered proliferation of granulosa cells or
      of altered oocyte growth in mutant mice. Other features of folliculogenesis, such
      as initiation of follicular growth, total follicle population and follicular
      atresia, were not affected by the mutation. Analysis of in vitro folliculogenesis
      did not reveal other differences between wild type and mutant mice. It is
      concluded that the Kit(W-lacZ) mutation affects the expression of KIT and KIT
      LIGAND proteins, resulting in alterations in granulosa cell proliferation and/or
      oocyte growth in preantral follicles.

PMID- 11226048
TI  - A comparative study of sperm production in two species of Australian arid zone
      rodents (Pseudomys australis, Notomys alexis) with marked differences in testis
      size.
AB  - The plains rat, Pseudomys australis, and the spinifex hopping mouse, Notomys
      alexis, show marked differences in the size of their testes and in the number of
      spermatozoa within the epididymides. In the present study, the dynamics of sperm
      production and the duration of sperm transit along the male excurrent ducts were
      compared between these two species. The durations of the cycle of the
      seminiferous epithelium, spermatogenesis and sperm transit were determined by
      tracking cells using autoradiography after [(3)H]thymidine incorporation. Daily
      sperm production was determined from counts of testicular spermatids after
      homogenization and further estimates of sperm transit were obtained by dividing
      sperm reserves within the various regions of the extratesticular ducts by the
      daily sperm production of the attached testis. In the plains rat, the mean
      duration of the cycle of the seminiferous epithelium was 11.2 days, the duration
      of spermatogenesis was 45 days, daily sperm production was 2.6 x 10(7)
      spermatozoa per gram of testis and epididymal transit of spermatozoa took
      approximately 9 days (caput 0.8 days; corpus 1.5 days; cauda 6.5 days). In
      contrast, in the hopping mouse, the mean duration of the cycle of the
      seminiferous epithelium was 14 days, the duration of spermatogenesis was 56 days
      and daily sperm production per gram of testis was < 1.0 x 10(7). Epididymal
      transit of spermatozoa was completed in about 4 days (caput + corpus < 1 day;
      cauda 3 days); however, spermatozoa may be stored for an additional 1.5-2.0 days
      in the vas deferens. These results indicate that, in addition to small testes,
      the hopping mouse shows a low efficiency of sperm production, a relatively long
      duration of spermatogenesis and rapid passage of spermatozoa through the
      epididymis, all of which contribute to low epididymal sperm counts. These data
      are considered in relation to interspecific differences in sperm competition.

PMID- 11226049
TI  - Effect of the factor inhibiting germinal vesicle breakdown on the disruption of
      gap junctions and cumulus expansion of pig cumulus-oocyte complexes cultured in
      vitro.
AB  - The present study was undertaken to explore the regulatory mechanisms for meiotic
      resumption of pig cumulus-oocyte complexes (COCs) by assessing the nuclear status
      of oocytes, the degree of gap junction cell-to-cell communication and cumulus
      expansion after culture of various numbers of COCs in 10 microl droplets of
      medium for 24 h. Gap junction communication was examined by confocal laser
      scanning microscopy after injection of a fluorescent dye, lucifer yellow, into
      the oocytes. When one, three or six COCs were cultured in a 10 microl droplet,
      germinal vesicle breakdown was observed in > 70% of oocytes; increasing the
      number of COCs in a droplet further actually decreased the proportion of oocytes
      undergoing germinal vesicle breakdown (10 COCs: 49%; 20 COCs: 21%; 40 COCs: 13%).
      When six COCs were cultured in a 10 microl droplet of conditioned medium
      (prepared previously by culturing 20 intact and oocytectomized COCs for 24 h),
      the proportion of oocytes undergoing germinal vesicle breakdown was significantly
      reduced compared with the proportion in fresh medium. An increase in the
      proportion of category 1 COCs (all gap junctions within cumulus cells and between
      cumulus cells and oocyte are functionally maintained) was achieved by increasing
      the number of COCs cultured in a 10 microl droplet. The addition of conditioned
      medium to the fresh medium at a concentration of 50% significantly inhibited
      cumulus expansion. From these results, it is concluded that the factors secreted
      by cumulus cells regulate the disruption of gap junctions and cumulus expansion,
      and concurrently control the incidence of germinal vesicle breakdown in pig COCs.

PMID- 11226050
TI  - Effects of genistein on the periovulatory expression of messenger ribonucleic
      acid for matrix metalloproteinases and tissue inhibitors of metalloproteinases in
      the rat ovary.
AB  - The matrix metalloproteinases (MMPs) play critical roles in the ovulatory
      process. Their expression and activity, together with those of the endogenous
      tissue inhibitors of metalloproteinases (TIMPs), are stimulated by LH. The LH
      surge initiates a cascade of events resulting in ovulation and formation of the
      corpus luteum via activation of protein kinases A and C, as well as tyrosine
      kinases. In vitro perfused rat ovaries were untreated, or treated with LH (0.2
      microg ml(-1)) plus 0.2 mmol 3-isobutyl-1-methylxanthine l(-1) with 0, 10 or 100
      micromol genistein l(-1) (an inhibitor of tyrosine kinases) to assess whether
      tyrosine kinases are mediators of the LH-stimulated increase in ovarian
      expression of the MMPs and TIMPs. After 10 h of perfusion, ovaries were collected
      and frozen until RNA isolation. Northern and RNase protection analyses were used
      to measure mRNA encoding collagenase 3, gelatinases A and B, and TIMPs-1, -2 and 
      3. Treatment with LH plus 3-isobutyl-1-methylxanthine resulted in a two- and
      fivefold increase in mRNA encoding collagenase 3 and TIMP-1, respectively (P <
      0.05). Treatment with 100 micromol genistein l(-1) blocked the LH-stimulated
      increase in collagenase 3 (0.012 +/- 0.002 versus 0.028 +/- 0.005 relative units
      for 100 micromol genistein l(-1) versus LH; P < 0.05), whereas neither dose of
      genistein affected LH-induced TIMP-1 expression. LH alone or with genistein did
      not alter the expression of mRNA encoding TIMP-2 and TIMP-3, or mRNA encoding
      gelatinases A and B. These data indicate that tyrosine kinases play a role in the
      LH-induced tissue remodelling required for ovulation by mediating the LH
      stimulated expression of collagenase 3.

PMID- 11226051
TI  - Characterization of northern pintail (Anas acuta) ejaculate and the effect of
      sperm preservation on fertility.
AB  - Northern pintail duck semen and sperm traits were characterized, and the
      fertility of cold-stored spermatozoa was investigated using artificial
      insemination. Excellent quality ejaculates containing high proportions of motile
      spermatozoa were collected from drakes within 20 s by a massage technique. Semen
      was collected in Beltsville poultry semen extender, pooled and cold-stored (4
      degrees C) for 0, 24, 48 or 72 h. Hens were inseminated with 100 microl twice a
      week, and eggs were assessed for fertilization and hatch success. Fertilization
      success was similar (P > 0.05) for semen cold-stored for 0 (51.6%), 24 (51.5%),
      48 (41.1%) and 72 h (22.3%; P > 0.05). Similar (P > 0.05) percentages of
      fertilized eggs hatched to live offspring (73.1, 71.4, 87.0 and 80.0%,
      respectively). Fresh semen was also equilibrated with 1 or 4% dimethylsulphoxide
      or glycerol, and cryopreserved at the following rates: (1) approximately 60
      degrees C min(-1) (in liquid nitrogen [LN(2)] vapour) for 10 min; (2) 1 degrees C
      min(-1) to -20 degrees C, LN(2) vapour for 10 min; and (3) 1 degrees C min(-1) to
      -35 degrees C, all followed by immersion in LN(2). After thawing for 30 s at 37
      degrees C or 20 min at 4 degrees C, sperm motility and viability were assessed.
      The highest numbers of motile spermatozoa were recovered after slow-fast freezing
      (2) and thawing at 0 degrees C (P < 0.05), but survival was inadequate to allow
      artificial insemination. Nonetheless, cold storage provides an effective means of
      short-term storage with no loss of fertility in this waterfowl species.

PMID- 11226052
TI  - Ovarian steroid hormone production in a multiple ovulating male line and a single
      ovulating traditional line of turkeys.
AB  - Ovarian production of oestradiol and progesterone was investigated in a single
      ovulating traditional line and a multiple ovulating male line of turkeys. The
      oestradiol output from small follicles in response to LH stimulation and the
      aromatase activity of the residual ovary were also compared. The multiple
      hierarchy of follicles in the male line was shown to consist of a series of
      follicles of a similar size and stage of physiological maturation. The follicles
      of the traditional line produced significantly greater quantities of oestradiol
      than those of the male line. Impaired oestradiol production may have resulted in
      the lower plasma oestradiol concentration observed in the male line. There was no
      difference in follicular progesterone output between the traditional-line and
      male-line turkeys. The oestradiol output of whole small white follicles in
      response to LH stimulation was similar in the two lines and the depressed
      steroidogenesis of the male line was not changed. The aromatase activity of the
      small follicles was also lower in the male line, and there was no evidence that
      the male line ovary produced oestradiol in quantities proportional to its size.
      The results demonstrated that the hierarchy of follicles in the male line
      consisted of groups of follicles of similar mass and hormone output and indicated
      that selection for increased meat yield may have resulted in reduced ovarian
      steroidogenesis in male-line turkeys, in comparison with traditional, unselected
      turkeys.

PMID- 11226053
TI  - Use of antibodies against LH receptor, 3beta-hydroxysteroid dehydrogenase and
      vimentin to characterize different types of testicular tumour in dogs.
AB  - Testicular tumours in dogs are of Sertoli cell, Leydig cell or germinal origin
      and mixed tumours are also frequently observed. The cellular components of mixed
      tumours are usually identified by histological examination but sometimes this is
      difficult. In this study, a panel of specific antibodies was used to identify the
      different cell types in testicular tumours by immunohistochemistry. Leydig cells
      were identified using an antibody against the LH receptor and an antibody against
      the steroidogenic enzyme 3beta-hydroxysteroid dehydrogenase (3beta-HSD), both of
      which are characteristic of Leydig cells in testes. Sertoli cells were identified
      using an antibody against the intermediate filament vimentin. Seminoma cells did
      not stain with any of these antibodies. Vimentin was used only in histologically
      complex cases. Eighty-six tumours, diagnosed histologically as 29 Sertoli cell
      tumours, 25 Leydig cell tumours, 19 seminomas and 13 mixed tumours, were studied.
      Feminization was observed in 17 dogs. Leydig cell tumours stained positively with
      the antibodies against the LH receptor and 3beta-HSD, whereas seminomas and
      Sertoli cell tumours were negative (unstained). The antibody against vimentin
      stained both Sertoli and Leydig cells, and tumours arising from these cells, but
      not seminomas. Immunohistochemistry revealed that three tumours identified
      histologically as Sertoli cell tumours were actually Leydig cell tumours. In 14
      dogs the histological diagnosis appeared to be incomplete, as mixed tumours
      instead of pure types of tumours were identified in 11 dogs, and in three dogs
      mixed tumours appeared to be pure types. Hence, the histological diagnosis was
      insufficient in approximately 20% of dogs. Furthermore, immunohistochemical
      analysis of testis tumours revealed that feminization occurred in dogs with
      Sertoli cell tumours or Leydig cell tumours and their combinations, but not in
      dogs with a seminoma. In conclusion, incubation with antibodies against LH
      receptor and 3beta-HSD proved to be a consistently reliable method for
      identification of Leydig cell tumours in dogs. Vimentin can be used to
      discriminate between Sertoli cell tumours and seminomas. Overall, this panel of
      antibodies can be very useful for determination of the identity of testicular
      tumours in which histological characterization is complicated and the
      pathogenesis of feminization is not clear.

PMID- 11226055
TI  - Novel method for intrafollicular pressure measurements in the rat ovary:
      increased intrafollicular pressure after hCG stimulation.
AB  - The ovulatory process in the rat comprises a period of about 12-15 h, from the
      time of the preovulatory LH surge to follicular rupture and extrusion of the
      oocyte. Follicular rupture is most likely caused, at least in part, by decreased
      tensile strength at the follicular apex due to degradation of collagen fibres of
      the extracellular matrix. It has been debated whether changes in intrafollicular
      pressure occur during the ovulatory process and whether such changes facilitate
      rupture of the follicle. In the present study, rats were primed with equine
      chorionic gonadotrophin (eCG, 10 iu) followed by hCG (10 iu) 48 h later. The
      intrafollicular pressure in the preovulatory follicle was recorded during 1 h at
      distinct time phases of the ovulatory process by use of an active servo-null
      pressure system based on the proportionality between electrical resistance and
      pressure within the tip of an inserted micropipette. The basal intrafollicular
      pressure was 16.6 +/- 1.0 mm Hg at the preovulatory phase (48 h after eCG) and
      increased gradually throughout the ovulatory process to 21.4 +/- 2.4 mm Hg at 4-7
      h after hCG (mid-ovulatory phase) and 23.9 +/- 1.9 mm Hg at 8-12 h after hCG
      (late ovulatory phase; significantly higher (P < 0.01) than the preovulatory
      phase). Short-term peaks of increased pressure, possibly representing
      contractility, were not detected in follicles of the preovulatory phase, but were
      seen in most follicles of the mid- and late ovulatory phases. The mean amplitude
      of the short-term pressure increases was 12.3 +/- 3.2 mm Hg and the increases
      occurred at intervals of 24.7 +/- 3.6 s. These short-term increments in
      intrafollicular pressure were still present after hysterectomy had been
      performed. The wall tension index was calculated by measuring the follicular size
      and estimating the thickness of the follicle wall. The index increased from 93.9
      +/- 13.3 at the preovulatory phase to 207.3 +/- 47.7 (mid-ovulatory phase) and to
      significantly higher values at the late ovulatory phase (320.9 +/- 33.5). In
      conclusion, this study shows that there is an increase in intrafollicular
      pressure in the ovulating follicle of the rat ovary during the late stages of the
      ovulatory process, and that short-term increases in intrafollicular pressure
      occur during the late phase of the ovulatory process. These changes in pressure
      may be essential for follicular rupture to proceed normally.

PMID- 11226054
TI  - Leucocyte proliferation in the bovine corpus luteum.
AB  - Leucocytes vary in type and number during the lifespan of a corpus luteum. The
      aim of this study was to determine whether there is an increase in the number of
      lymphocytes and macrophages as a result of local proliferation. Bovine corpora
      lutea were classified into stages of development, secretion and regression. A new
      double immunolabelling method was established for nuclear Ki-67 antigen (a marker
      for cell proliferation) and for leucocyte surface antigens (detection of CD2-,
      CD3-, CD4-, CD8-positive lymphocytes and CD14-positive monocytes). Differential
      cell counting was performed. Between the stages of development and regression
      there was an increase in the number of T-lymphocytes and macrophages. The
      percentage of proliferating leucocytes in relation to the total number of
      proliferating cells was approximately 20% at the stage of advanced secretion and
      70% at late regression. The increase in the number of proliferating leucocytes at
      late regression was due to CD14-positive macrophages. These macrophages migrated
      from small blood vessels into the septa of corpora lutea at the early stage of
      regression. Macrophages showed local proliferation in the late stage of
      regression when capillaries were no longer present. It is concluded that the
      physiological involution of the corpus luteum is an inflammatory-like condition,
      which includes local proliferation of monocytes.

PMID- 11226056
TI  - Effects of feeding tuna oil on the lipid composition of pig spermatozoa and in
      vitro characteristics of semen.
AB  - The aim of the present study was to characterize the effects of feeding tuna oil
      on the lipid and fatty acid composition of boar spermatozoa and to relate changes
      in composition to boar semen characteristics. Ten boars were paired by age and
      allocated to one of two diets (five boars per diet). The diets, which were
      offered for 6 weeks, consisted of a basal diet that was either unsupplemented or
      supplemented with 30 g tuna oil kg(-1) diet. Adding tuna oil to the diet
      increased the ether extract concentration of the diets fed from 65 to 92 g kg(-1)
      dry matter and supplied 10.5 g long chain polyunsaturated (n-3) fatty acids per
      100 g total fatty acids. There were no changes in semen fatty acid composition
      after 3 weeks of feeding tuna oil. However, after 5 and 6 weeks, the proportions
      (g per 100 g total fatty acids) of 22:6(n-3) in sperm phospholipid fatty acids
      were increased from 34.5 to 42.9 g by feeding tuna oil and 22:5(n-6) decreased
      from 29.8 to 17.9 g. No changes were observed in other sperm lipids or seminal
      plasma phospholipids as a result of the diets fed. Feeding tuna oil increased the
      proportion of spermatozoa with progressive motility and with a normal acrosome
      score and reduced the proportion of spermatozoa with abnormal morphologies.

PMID- 11226057
TI  - Effects of bilateral ganglionectomy and melatonin replacement on seasonal rhythm
      of testicular activity in Zembra Island wild rabbits (Oryctolagus cuniculus).
AB  - This study examined the effects of subcutaneous melatonin implants on testicular
      activity (testis volume and plasma testosterone) in wild rabbits (Oryctolagus
      cuniculus) captured on Zembra Island (North Tunisia) and maintained in natural
      temperature and photoperiod conditions. The period of testicular activity was 2
      months longer in intact animals with melatonin implants than in intact animals
      without melatonin implants. After bilateral superior cervical ganglionectomy,
      testicular activity was inhibited and no spontaneous recrudescence in gonadal
      function was observed during the 13 months of the experiment, demonstrating the
      absence of an endogenous circannual rhythm of reproductive function in this
      species. Renewed testicular activity was observed 2 months after the insertion of
      melatonin implants in ganglionectomized animals. These results confirm that
      testicular activity is stimulated by short days in late autumn and that melatonin
      reactivates the reproductive axis in this species. This finding is in contrast to
      that in continental populations of wild rabbits in which reproduction is
      inhibited by short days or melatonin. These results are discussed in terms of
      insularity and may reflect the geographical isolation of this population.

PMID- 11226058
TI  - Maternal-conceptus signalling during early pregnancy in mares: oestrogen and
      insulin-like growth factor I.
AB  - Embryonic production of oestrogen is thought to play an important role in
      conceptus-maternal signalling during early pregnancy in mares, and may be
      regulated in an autocrine or paracrine fashion by insulin-like growth factor I
      (IGF-I). In this study, the hypothesis that IGF-I stimulates embryonic oestrogen
      synthesis, which in turn stimulates uterine IGF-I secretion was tested. Specific
      sources of IGF-I in the uterine lumen were characterized. Preimplantation
      embryos, uterine biopsies, and uterine flush fluids were collected on day 13 of
      pregnancy. Embryos were cultured whole for 24 h, or dispersed and incubated in
      serum-free culture medium supplemented with androstenedione or testosterone (0-10
      microg ml(-1)) and IGF-I (0-100 microg ml(-1)). Oestrogen synthesis was increased
      by addition of androgen, but there was no dose-dependent effect of IGF-I.
      Endometrial explants were cultured for 24, 48 and 72 h in serum-free medium
      supplemented with oestradiol. IGF-I was measured by radioimmunoassay in embryo
      conditioned medium, explant culture medium, blastocoelic fluid, concentrated (x
      100) uterine flush fluid and endometrial-tissue homogenate. Both the embryo and
      endometrium produced significant quantities of IGF-I, indicating a role for this
      growth factor in autocrine-paracrine signalling during early pregnancy. However,
      secretion of IGF-I by endometrial explants was not modulated by oestrogen.

PMID- 11226059
TI  - Formation of Fallopian tubal fluid: role of a neglected epithelium.
AB  - Fluid produced and secreted by the Fallopian tube provides the environment in
      which gamete transport and maturation, fertilization and early embryo development
      occur. This review describes the composition of oviductal fluid in terms of ions
      and nutrients such as glucose, lactate, pyruvate and amino acids. The function of
      oestrogen-specific glycoprotein is discussed. The mechanisms of fluid secretion
      and agents known to influence fluid production and secretion are described.
      Clinical implications of abnormal oviductal fluid production and secretion in
      hydrosalpinx and pelvic inflammatory disease are also discussed.

PMID- 11226060
TI  - Proliferation and differentiation of spermatogonial stem cells.
AB  - Spermatogonial stem cells (A(s) spermatogonia) are single cells that either renew
      themselves or produce A(pr) (paired) spermatogonia predestined to differentiate.
      In turn, the A(pr) divide into chains of A(al) (aligned) spermatogonia that also
      divide. The ratio between self-renewal and differentiation of the stem cells is
      regulated by glial cell line-derived neurotrophic factor produced by Sertoli
      cells, while the receptors are expressed in stem cells. A(s), A(pr) and A(al)
      spermatogonia proliferate during part of the epithelial cycle forming many A(al)
      spermatogonia. During epithelial stage VIII, almost all A(al) spermatogonia, few
      A(pr) and very few A(s) spermatogonia differentiate into A1 spermatogonia. A
      number of molecules are involved in this differentiation step including the stem
      cell factor-c-kit system, the Dazl RNA binding protein, cyclin D(2) and retinoic
      acid. There is no fine regulation of the density of spermatogonial stem cells and
      consequently, in some areas, many A1 and, in other areas, few A1 spermatogonia
      are formed. An equal density of spermatocytes is then obtained by the apoptosis
      of A2, A3 or A4 spermatogonia to remove the surplus cells. The Bcl-2 family
      members Bax and Bcl-x(L) are involved in this density regulation. Several
      mechanisms are available to cope with major or minor shortages in germ cell
      production. After severe cell loss, stem cell renewal is preferred above
      differentiation and the period of proliferation of A(s), A(pr) and A(al)
      spermatogonia is extended. Minor shortages are dealt with, at least in part, by
      less apoptosis among A2-A4 spermatogonia.

PMID- 11226061
TI  - Regulation and manipulation of angiogenesis in the primate corpus luteum.
AB  - Intense physiological angiogenesis occurs during the early stages of luteal
      development, providing a model in which the complex processes regulating the
      angiogenic pathway may be studied. Here, a working hypothesis is presented to
      explain the diverse changes in the vasculature of the corpus luteum that occur
      over a short period, based around changes in vascular endothelial growth factor,
      the angiopoietins and matrix metalloproteinases. An illustration is given of how
      angiogenesis can be monitored in a primate model and how the role of individual
      angiogenic factors such as vascular endothelial growth factor may be explored in
      vivo. Because of the marked effect of inhibition of angiogenesis on luteal
      function, it is predicted that the normal processes of follicular development,
      ovulation and luteal function could all be profoundly influenced by the
      manipulation of angiogenesis.

PMID- 11226062
TI  - Pituitary tumours.
AB  - Pituitary tumours are a common type of intracranial neoplasm and, depending on
      the cell type of origin, have diverse endocrine and reproductive effects. The
      developmental biology of the different cell types is understood to result from a
      sequential activation of a cascade of transcription factors, and mutations in
      these factors result in various forms of hypopituitarism. Tumours in the
      pituitary gland arise from activation of dominantly acting oncogenes such as gsp,
      or from loss of function of a series of tumour suppressor genes such as MEN1.
      Abnormal patterns of DNA methylation may be implicated in the allelic losses that
      cause tumour suppressor gene silencing. The different clinically recognized types
      of pituitary tumour are currently treated by medical therapies such as dopamine
      and somatostatin agonists, surgery or radiotherapy. However, these treatments are
      not entirely satisfactory and recent advances in gene therapy may offer valuable
      new therapeutic opportunities for patients with aggressive tumours that fail to
      respond to traditional approaches.

PMID- 11226063
TI  - Isolation and partial characterization of the outer dense fibres and fibrous
      sheath from the sperm tail of a marsupial: the brushtail possum (Trichosurus
      vulpecula).
AB  - The flagellum of a mammalian spermatozoon consists of a central axoneme
      surrounded by two cytoskeletal structures, the outer dense fibres and the fibrous
      sheath, which may aid in sperm motility or stability. In this study the outer
      dense fibres and fibrous sheath were isolated and partially characterized in a
      marsupial species, the brushtail possum (Trichosurus vulpecula). Spermatozoa from
      the cauda epididymidis were decapitated by sonication, and the head and tail
      fractions were separated by centrifugation over a 20, 40 and 60% (w/v) sucrose
      density gradient. After confirming sperm tail purity by Nomarski microscopy, the
      tails were incubated in either SDS-dithiothreitol to isolate the outer dense
      fibres or urea-dithiothreitol to isolate the fibrous sheaths. Purified outer
      dense fibres and fibrous sheaths were solubilized in SDS and beta-mercaptoethanol
      and proteins were separated by one-dimensional PAGE. Coomassie blue staining
      showed that the outer dense fibres were composed of seven major proteins
      (molecular masses: 73, 58, 55, 54, 52, 41 and 16 kDa), and the fibrous sheath was
      composed of 12 major proteins (molecular masses: 106, 76, 66, 62, 55, 53, 52, 46,
      40, 30, 28 and 16 kDa). A polyclonal antibody to the fibrous sheath proteins
      showed strong crossreactivity with those of fibrous sheath from spermatozoa of
      several other marsupial species, as well as those from laboratory rats.
      Subsequent western blotting identified the immunoreactive 76 and 62 kDa proteins
      from all species, thus indicating their high conservation between species. No
      crossreactivity of the fibrous sheath antibody to any other cytoskeletal
      structures, including the outer dense fibres, mid-piece fibre network or
      connecting laminae, or to the acrosome or underlying subacrosomal material, was
      evident, indicating that the fibrous sheath proteins are localized to this
      structure alone. Further work is in progress to determine the extent of homology
      of these proteins to those in eutherian mammals.

PMID- 11226064
TI  - In vitro maturation, fertilization and embryo development after ultrarapid
      freezing of immature human oocytes.
AB  - The purpose of this study was to determine the rates of maturation, fertilization
      and embryo development of ultrarapidly frozen immature oocytes (immature cumulus
      oocyte complexes; COCs) obtained from antral follicles in ovaries of patients
      with chocolate ovarian cysts. The COCs were cryopreserved by a vitrification
      method using 5.5 mol ethylene glycol l (-1) plus 1.0 mol sucrose l (-1) in
      Dulbecco's PBS (DPBS). The survival, maturation and fertilization rates, and the
      percentage of embryos developing to the two-cell stage were 59, 64, 70 and 71%,
      respectively. No significant differences were noted in the rates of maturation,
      fertilization and embryo development between control and cryopreserved oocytes.
      Two embryos that developed from cryopreserved oocytes of the oocyte donor
      programme were selected for transfer into the uterus of a recipient with
      premature ovarian failure, after the recipient had received steroid replacement.
      A biochemical pregnancy occurred in the recipient after embryo transfer. These
      results indicate that immature oocytes can survive after cryopreservation and
      subsequently can be cultured to mature oocytes that are capable of undergoing
      fertilization in vitro and developing into embryos.

PMID- 11226065
TI  - Changes in sperm quality and lipid composition during cryopreservation of boar
      semen.
AB  - The effect of cryopreservation on boar sperm viability, motility, lipid content
      and antioxidant enzymatic activities was studied. Three classes of semen were
      determined according to a cluster analysis on the basis of the proportion of live
      and dead cells after freezing and thawing. The classes identified were: high (H,
      n = 4), average (A, n = 12) and low (L, n = 3) viability. The concentration of
      sperm cells decreased from class H to A to L. Fresh semen samples with higher
      viability and a higher proportion of motile cells also maintained better quality
      after the freezing and thawing procedure. Sperm viability and motility in both
      fresh and thawed samples were similar in classes H and A, while significantly
      lower values were measured in class L. The relative decrease in sperm viability
      and motility after cryopreservation increased from class H to A to L. The lipid
      content of spermatozoa (micrograms per 10(9) cells) increased significantly after
      freezing and thawing in classes H and A but not in class L. This result indicated
      that active sperm lipid metabolism might be responsible for the increase in lipid
      content. Phospholipid and triacylglycerol contents increased whereas free
      cholesterol content decreased after thawing. The fatty acid composition of fresh
      spermatozoa was similar in all three classes. The proportion of polyunsaturated
      fatty acids decreased significantly after freezing and thawing, indicating
      contamination from the diluent or peroxidation. After freezing and thawing,
      superoxide dismutase activity in spermatozoa was significantly higher in class L
      than in classes H and A, which did not differ from each other.

PMID- 11226066
TI  - Nitric oxide synthases in pregnant rat uterus.
AB  - The conversion of [14C]arginine into [14C]citrulline as an indicator of nitric
      oxide synthesis was studied in uteri isolated from rats on different days of
      gestation, after labour and during dioestrus. Nitric oxide synthesis was present
      in uterine tissues isolated at each stage of gestation and also in tissues
      collected during dioestrus and after labour. Expression of neuronal nitric oxide
      synthase was not detectable at any of the stages studied. Endothelial nitric
      oxide synthase was present at all the stages studied, but there was a significant
      increase on day 13 of gestation and a decrease thereafter, with the lowest
      expression recorded on the day after labour. Inducible nitric oxide synthase
      expression in rat uteri increased substantially during pregnancy, with the
      highest expression on day 13 of gestation; expression decreased at term and after
      labour. The changes in expression of inducible nitric oxide synthase were
      coincident with the changes in nitric oxide synthase activity in uteri treated
      with aminoguanidine. Thus, these findings indicate that an increase in expression
      of inducible nitric oxide synthase in the uterus may be important for maintenance
      of uterine quiescence during pregnancy and its decrease near the time of labour
      could have an effect on the start of uterine contractility.

PMID- 11226068
TI  - Ultrasonographic imaging of the reproductive organs of the female bottlenose
      dolphin, Tursiops truncatus aduncas.
AB  - Routine ultrasonographic examination of the reproductive tract was performed for
      periods of up to 10 years in ten female bottlenose dolphins (Tursiops truncatus
      aduncas) in Hong Kong. The ovaries could be reliably and repeatedly identified,
      lying close to the body surface, in the angle formed by the rectus abdominus and
      hypaxialis lumborum muscles, and were most easily located by scanning in the
      transverse plane from the proximal end of the genital slit towards the head. The
      ovaries are ovoid, with a relatively hypoechoic cortex around a central echogenic
      mesovarium. The echogenicity of the ovarian parenchyma appeared to increase with
      increasing age. This may be the result of age-related changes, such as increased
      fat deposition or fibrosis, or of ovarian 'scars' from multiple ovulations. Small
      antral follicles, developing follicles and corpora lutea can be identified within
      the ovarian cortex. Owing to its shape and lack of a definitive border, plus the
      close relationship to the intestines, the contents of which may obstruct the
      ultrasound beam, the non-pregnant uterus was not so easily visualized. The
      endometrium was poorly differentiated and difficult to see. To date, examination
      of the uterus using ultrasonography has provided little information about
      endometrial changes during the ovarian cycle in this group of dolphins. Real-time
      diagnostic ultrasonography provides a means to image the morphology of the
      reproductive organs in live female dolphins directly and provides a valuable
      means of assessing reproductive events in this species.

PMID- 11226067
TI  - Influence of genetic dissimilarity of mother and fetus on progesterone
      concentrations in pregnant mice and adaptive features of offspring.
AB  - Concentrations of progesterone in blood plasma and tissue were studied in
      pregnant mice of strains BALB/cLac and C57BL/6J. Both intra- and interstrain
      mating and embryo transplantations were used as models of homo- and heterotopic
      pregnancy. On day 4 of heterotopic pregnancy, plasma progesterone concentrations
      of females of both strains were higher than those in females of both strains
      undergoing homotopic pregnancy. In addition, tissue progesterone content of
      hybrid embryos was higher than that of purebred embryos. Adrenocortical responses
      to social conflict as indicators of stress resistance were studied in progeny
      aged 2-3 months. There was a minimal increase in plasma glucocorticoid
      concentrations in heterotopic transplantants after 15 min pair-matching tests and
      30 min crowding compared with those of other progeny, including purebred male
      mice of BALB/cLac and C57BL/6J strains, homotransplantants and reciprocal
      hybrids. Thus, genetic dissimilarity of mother and fetuses plays an important
      role in progesterone provision during pregnancy and also modifies development of
      progeny.

PMID- 11226069
TI  - Effect of finadyne on oestradiol-induced ovarian oxytocin and uterine PGF2alpha
      secretory systems on day 15 after oestrus in ovarian autotransplanted ewes.
AB  - This study was undertaken to determine whether induction of ovarian oxytocin
      after oestradiol treatment on day 15 after oestrus is mediated through
      prostaglandin secretion by blocking prostaglandin synthesis using finadyne, an
      inhibitor of the cyclo-oxygenase pathway. Nine ewes with ovarian autotransplants
      were assigned randomly to receive an i.m. injection of either oestradiol benzoate
      (50 microg) in peanut oil ( n= 5) or oestradiol benzoate plus finadyne (2.2 mg kg
      (-1)) ( n= 4) at 3 h intervals starting at the time of oestradiol injection.
      Blood samples were collected from the ovarian and contralateral jugular veins at
      30 min intervals for 6 h before and at 15 min intervals for up to 9 h after the
      oestradiol and finadyne injections. The secretion rate of ovarian progesterone
      remained high in all ewes, thus indicating the presence of a functional corpus
      luteum. Peripheral oestradiol concentrations were significantly (P < 0.001)
      higher during the 9 h after oestradiol injection in both groups. None of the
      oestradiol-finadyne-treated ewes showed significant pulses in either ovarian
      oxytocin secretion or release of the prostaglandin F(2alpha) metabolite 13,14
      dihydro-15-keto PGF(2alpha) (PGFM) after injections. In ewes treated with
      oestradiol only, at least one detectable pulse of ovarian oxytocin and jugular
      PGFM was observed with mean +/- SEM amplitude of 17.7 +/- 7.29 ng min (-1) and
      237.18 +/- 43.13 pg ml (-1), respectively. The areas under the curve for ovarian
      oxytocin and jugular PGFM pulses were significantly increased after oestradiol
      treatment. These findings demonstrate that initiation of the arachidonic acid
      cascade is important for the secretion of oxytocin after oestrogen treatment.

PMID- 11226070
TI  - Synthesis and glycosylation of CD52, the major 'maturation-associated' antigen of
      rat spermatozoa, in the cauda epididymidis.
AB  - A western and lectin blot analysis was performed of the major 'maturation
      associated' antigen of rat spermatozoa, which is the rat counterpart of human
      CD52. In the absence of a suitable antibody, direct study of this approximately
      26 kDa antigen, named previously SMemG, had been difficult. In the present study,
      these problems were overcome by raising a polyclonal antibody against a
      chemosynthetic peptide predicted from the cDNA sequence of the antigen. The
      antibody bound to a glycoprotein of rat cauda epididymidal tissue and
      spermatozoa, this glycoprotein was cleaved by phosphatidylinositol-specific
      phospholipase C and, after deglycosylation, was reduced to approximately 6 kDa.
      Northern blot analysis confirmed that the CD52 mRNA was transcribed only post
      testicularly, and antibody binding to testicular and sperm proteins of different
      molecular masses was shown to be nonspecific. Flow cytometry also indicated that
      the antigen was inserted into the sperm membrane during epididymal transit.
      Moreover, despite the presence of CD52 mRNA in all parts of the rat epididymis,
      only the 'long' mRNA molecules of the cauda region were efficiently translated
      and the antigen glycosylated, indicating that expression of rat CD52 is regulated
      on a post-transcriptional level. Lectin binding and deglycosylation studies
      supported the contention that there is extensive mucin-type O-glycosylation of
      rat CD52. In rats, there was no indication of complex N-linked carbohydrates
      similar to those described for human CD52.

PMID- 11226071
TI  - Seasonal changes in bovine fertility: relation to developmental competence of
      oocytes, membrane properties and fatty acid composition of follicles.
AB  - Follicle dynamics and oocyte viability in Holstein primiparous and multiparous
      cows and the relationships between fertility and the biochemical and physical
      properties of oocyte membranes with season were examined. The conception rates of
      primiparous (n = 70 885) and multiparous (n = 143 490) cows differed, peaking in
      the winter and decreasing in the summer. The number of follicles 3-8 mm in
      diameter per ovary was higher in winter (19.6) compared with summer (12.0).
      However, in winter the percentage of ovaries with fewer than ten follicles per
      ovary was 16%, in contrast to 50% in summer. After aspiration of follicles, 7.5
      oocytes per ovary were found in winter and 5.0 oocytes per ovary in summer.
      Cleavage to the two- to four-cell stage after chemical activation was greater in
      winter than in summer; this was enhanced at the morula stage and embryo
      development to the blastocyst stage was significantly higher in winter than in
      summer. Determination of the lipid phase transition in oocyte membranes revealed
      a shift of 6 degrees C between summer and winter. Fatty acid composition of
      phospholipids from follicular fluid, granulosa cells and oocytes indicated that
      there was a higher percentage of saturated fatty acids during the summer and that
      the percentages of mono-unsaturated and polyunsaturated fatty acids were higher
      in oocytes and granulosa cells during the winter. Oocytes and granulosa cells had
      similar fatty acid compositions, in contrast to follicular fluid. These results
      may explain the differences in the ability of oocytes to develop to the
      blastocyst stage at different seasons. Thus, temperature changes may lead to
      changes in membrane properties, which, in turn, can influence oocyte function and
      fertility.

PMID- 11226072
TI  - Expression of mRNA for the LH and FSH receptors in mouse oocytes and
      preimplantation embryos.
AB  - The gonadotrophins LH and FSH are known to regulate gonadal growth, and
      differentiation, endocrine function and gametogenesis. The LH receptor is
      expressed in ovarian theca, granulosa and luteal cells, and in testicular Leydig
      cells. The FSH receptor is expressed only in ovarian granulosa cells and in
      testicular Sertoli cells. The expression of the FSH and LH receptors was analysed
      by RT-PCR to study the role of these receptors in early mouse development. After
      reverse transcription, strategically designed nested primers were used for
      amplification from cDNA. Transcripts for the receptors were present in mouse
      oocytes and preimplantation embryos. The presence of mRNA for FSH and LH
      receptors in oocytes, zygotes and preimplantation embryos indicates a potential
      role for the gonadotrophins in the modulation of meiotic resumption and
      completion of oocyte maturation, as well as a beneficial effect on early
      embryonic development in mice.

PMID- 11226073
TI  - Differences in follicular function of 3-month-old calves and mature cows.
AB  - After in vitro maturation, fertilization and development, the percentage of
      fertilized eggs developing to the blastocyst stage is usually lower in calves
      compared with cows. It is unknown whether this low ability to develop in vitro is
      inherent to calf oocytes or is caused by altered follicular maturation. The
      latter possibility was explored in the present study using two markers of
      follicle function: in vitro steroidogenesis by intact follicles and aromatase
      activity of follicular walls. Calf follicles > 9 mm in diameter had a low ability
      to produce oestradiol (ten times reduction compared with cows) despite a
      testosterone output by theca cells which was similar to that observed in cows.
      This finding is in agreement with the low aromatase activity of granulosa cells
      of calf follicles measured by tritiated water release assay. Qualitative and
      quantitative differences between calf and cow follicular fluids were assessed
      using western blotting (inhibin and activin, heat shock protein 90, Mullerian
      inhibiting substance) and assays (inhibin and activin) to determine whether this
      defective aromatase could be produced by alterations in the amounts of follicular
      proteins modulating aromatase (inhibin and activin, heat shock protein 90,
      Mullerian inhibiting substance). Western blotting of follicular fluid proteins
      demonstrated three main bands (59, 57 and < 30 kDa) and one minor band (34 kDa)
      with the anti-alpha inhibin antibody, whereas a single 18 kDa band was detected
      when an anti-beta inhibin antibody was used. Calf follicular fluid contained
      similar amounts of all main inhibin forms (alpha and beta) but a 34 kDa alpha
      inhibin form was missing. The amounts of dimeric inhibin were similar between
      cows and calves but small follicles from calves contained more activin. Single
      bands at 70 kDa (Mullerian inhibiting substance) and 90 kDa (heat shock protein
      90) were detected by western blotting. Mullerian inhibiting substance was missing
      from calf follicular fluid and heat shock protein 90 was present in smaller
      amounts in calf versus cow follicular fluid. None of the above differences could
      explain the defective aromatase of calf follicles. Two-dimensional separation of
      the [35S]-labelled proteins secreted by follicular walls originating from calf or
      cow follicles matched for size and follicle health was performed and 151 spots
      were observed on the master gel, which summarized all the spots present at least
      once. Fifteen spots were present in calves and not in cows. Quantitative
      differences were also detected with three spots containing more proteins in cows
      than in calves. Whether some of these proteins can alter maturation of follicles
      or oocytes requires further investigation.

PMID- 11226074
TI  - Demonstration of 2-unsaturated C19-steroids in the urine of female Asian
      elephants, Elephas maximus, and their dependence on ovarian activity.
AB  - Air-borne volatile substances have been demonstrated to signal oestrus, induce
      ovulation and synchronize ovarian activity in different mammals. An oestrous
      related pheromone of the female Asian elephant (Elephas maximus) is known to
      induce behavioural responses in elephant bulls. Additional data revealed that
      timing of oestrus in females with close social relationships tends to be
      synchronized. Therefore, urine from female Asian elephants might be expected to
      contain luteal phase-dependent volatile substances, which may function as
      additional chemical signals in this species. The aim of the present study was to
      identify such compounds and to investigate their pattern of excretion throughout
      the ovarian cycle. Urine samples were collected three times a week during the
      follicular phase and one to three times a week during the luteal phase from five
      adult female Asian elephants from a total of 13 non-conception cycles and one
      conception cycle, including the first 72 weeks of pregnancy. A simple headspace
      solid-phase microextraction method has been developed for quantification of
      urinary volatile substances and analysis was performed by gas chromatography. The
      comparison of urine collected during the follicular and the luteal phase
      indicated the presence of two luteal phase-dependent substances. Mass
      spectrometry was used to identify one substance as 5alpha-androst-2-en-17-one and
      a second substance as the corresponding alcoholic compound 5alpha-androst-2-en
      17beta-ol. The 5alpha-androst-2-en-17beta-ol and -17-one profiles reflected
      cyclic ovarian activity with clear (10-20-fold) luteal phase increases.
      Furthermore, measurements of both compounds were correlated positively with the
      concentration of urinary pregnanetriol and indicated cycle duration (15.1 +/- 1.2
      weeks) similar to that obtained from pregnanetriol measurements (15.2 +/- 1.6
      weeks). The results demonstrate the presence of two luteal phase-specific
      steroidal volatile compounds in elephant urine. One of the substances, 5alpha
      androst-2-en-17-one, has been demonstrated in human axillary bacterial isolates.
      The measurement of both volatile substances in elephant urine can be used for
      rapid detection of the stage of the ovarian cycle, as the analysis can be
      completed within 2 h.

PMID- 11226075
TI  - Inhibition of basal and stimulated progesterone synthesis by
      dichlorodiphenyldichloroethylene and methoxychlor in a stable pig granulosa cell
      line.
AB  - The effects of the insecticide dichlorodiphenyldichloroethylene (DDE) and
      methoxychlor in a stable pig granulosa cell line, JC-410, were investigated. The
      studies of DDE and methoxychlor were conducted in combination with studies of
      cholera toxin, the protein kinase A activator that stimulates cAMP and
      progesterone synthesis and gene expression of P450 cholesterol side chain
      cleavage (P450scc), which converts cholesterol to pregnenolone. Administration of
      DDE at 3000 and 10 000 ng ml (-1) was found to decrease progesterone synthesis
      0.49- and 0.25-fold, respectively, and to block the stimulatory effect of 100 ng
      cholera toxin ml (-1), after 24 h incubation. At 1-100 ng ml (-1), methoxychlor
      did not affect progesterone synthesis after 48 h incubation. However, 1000 ng
      methoxychlor ml (-1) decreased progesterone synthesis 0.32-fold, and both 100 and
      1000 ng methoxychlor ml (-1) blocked the stimulatory effect of cholera toxin. At
      3000 and 10 000 ng ml(-1), DDE decreased cAMP synthesis 0.66-and 0.36-fold,
      respectively. At 300, 3000 and 10 000 ng ml (-1), DDE also decreased cholera
      toxin-stimulated cAMP synthesis 0.84-, 0.68-, and 0.52-fold, respectively.
      Administration of 1-100 ng methoxychlor ml (-1) did not affect basal or cholera
      toxin-stimulated cAMP synthesis. Cholera toxin increased P450scc mRNA 1.4-fold
      after 24 h incubation, while 3000 and 10 000 ng DDE ml (-1) led to 0.39- and 0.18
      fold reductions, respectively. The stimulatory effect of cholera toxin on P450scc
      mRNA was blocked by 3000 and 10 000 ng DDE ml(-1). Cholera toxin increased
      P450scc mRNA 3.48-fold after 48 h incubation, while 100 and 1000 ng methoxychlor
      ml (-1) increased P450scc mRNA 1.79- and 3.0-fold, respectively, and further
      increased the stimulatory effect of cholera toxin 6.47- and 5.44-fold,
      respectively. The results of the present study indicate that DDE inhibits
      granulosa cell steroidogenesis by affecting cAMP production and P450scc gene
      expression. However, methoxychlor appears to inhibit steroidogenesis by a
      mechanism occurring before the conversion of cholesterol into pregnenolone.

PMID- 11226077
TI  - Thromboelastography: the next step.

PMID- 11226079
TI  - The influence of intravascular volume therapy with a new hydroxyethyl starch
      preparation (6% HES 130/0.4) on coagulation in patients undergoing major
      abdominal surgery.
AB  - A new hydroxyethyl starch (HES) preparation with a mean molecular weight of
      130,000 daltons and a degree of substitution of 0.4 shows favorable
      pharmacokinetic properties. We conducted a study of the influence of the new HES
      specification on coagulation and compared it with another colloidal intravascular
      volume replacement regimen using gelatin. According to a prospective, random
      sequence, 42 patients undergoing major abdominal surgery received either HES
      130/0.4 (n = 21) or gelatin (n = 21) until the first postoperative day (POD) to
      keep central venous pressure between 10 and 14 mm Hg. From arterial blood
      samples, standard coagulation variables were measured, and modified
      thrombelastogram (TEG) measurements using different activators were performed. A
      total of 2830 +/- 350 mL of gelatin and 2430 +/- 310 mL of HES 130/0.4 were
      administered until the morning of the first POD. The use of allogeneic
      blood/blood products and standard coagulation variables did not differ
      significantly between the two groups. After induction of anesthesia, all TEG data
      for both groups were within normal range. Coagulation time and maximum clot
      firmness did not change significantly in any TEG measurements during the study
      period. The kinetics of clot formation (clot formation time) significantly
      increased immediately after surgery, but without showing significant group
      differences. On the morning of the first POD, the clot formation time returned to
      almost normal levels, except for aprotinin-activated TEG(R). We conclude that
      administration of moderate doses of the new HES 130/0.4 preparation in patients
      undergoing major abdominal surgery results in similar coagulation alterations as
      those after using an established gelatin-based volume-replacement regimen.
      IMPLICATIONS: We compared the effects of infusion of a new hydroxyethyl starch
      preparation (6% hydroxyethyl starch; mean molecular weight 130,000 daltons;
      degree of substitution 0.4) on coagulation with a gelatin-based intravascular
      volume replacement regimen in patients undergoing major abdominal surgery. After
      moderate doses of hydroxyethyl starch (2430 +/- 310 mL until the morning of the
      first postoperative day), coagulation monitoring, including modified
      thrombelastography, did not show impaired hemostasis.

PMID- 11226080
TI  - Thromboelastography for monitoring prolonged hypercoagulability after major
      abdominal surgery.
AB  - Despite clinical and laboratory evidence of perioperative hypercoagulability,
      there are no consistent data evaluating the extent, duration, and specific
      contribution of platelets and procoagulatory proteins by in vitro testing. We
      tested the hypothesis that the parallel use of standard and abciximab
      cytochalasin D-modified thromboelastography (TEG) can assess 7 days'
      postoperative hypercoagulability and can estimate the independent contribution of
      procoagulatory proteins and platelets. Thromboelastograms were performed before
      surgery, at the end of surgery, 6 h after surgery, and on postoperative days 1,
      2, 3, and 7; they were analyzed for the reaction time and the maximal amplitude
      (MA). We calculated the elastic shear modulus of standard MA (G(t)) and modified
      MA (G(c)), which reflect total clot strength and procoagulatory protein
      component, respectively. The difference was an estimate of the platelet component
      (G(p)). There was a 10% perioperative increase of standard MA, corresponding to a
      50% increase of G(t) (P < 0.0001) and an 86%-90% contribution of the calculated
      G(p) to G(t). We conclude that serial standard and modified thromboelastography
      may reveal prolonged postoperative hypercoagulability and the independent
      contribution of platelets and procoagulatory proteins to clot strength.
      IMPLICATIONS: Postoperative hypercoagulability, occurring for at least 1 wk after
      major abdominal surgery, may be demonstrated by standard and modified
      thromboelastography. This hypercoagulability is not reflected by standard
      coagulation monitoring and seems to be predominantly caused by increased platelet
      reactivity.

PMID- 11226082
TI  - Hemodynamic-induced changes in aortic valve area: implications for Doppler
      cardiac output determinations.
AB  - Monitoring cardiac output (CO) by transesophageal echocardiography involves
      measurements of ascending aortic flow and an initial measurement of aortic valve
      area (AVA). Hemodynamic-induced changes in AVA are a potential source of error
      for this simplified method. Our goal was to quantify these changes in AVA and
      their effects on CO calculations. In 17 anesthetized patients, a dobutamine
      infusion was titrated to achieve a 50% increase in ascending aortic flow velocity
      (V(max)). Hemodynamic and echocardiographic variables, including V(max) and
      planimetry of AVA, were determined at baseline and at maximal dobutamine dose.
      Dobutamine produced a 3.0 +/- 1.4 L/min increase in CO, a 54.5% +/- 19.6%
      increase in V(max), and a 50.6% +/- 34.2% increase in systolic blood pressure.
      AVA increased by 4.3% +/- 2.6% during dobutamine infusion (P < 0.001). The
      simplified CO method, which does not account for increases in AVA, produced a
      0.32 +/- 0.24 L/min underestimation of CO. This investigation demonstrates
      hemodynamic-induced changes in AVA. The use of a single AVA measurement for all
      subsequent CO calculations introduces a clinically acceptable degree of error,
      supporting a simplified CO protocol requiring less probe manipulation and reduced
      procedural time. IMPLICATIONS: An intraoperative dobutamine infusion was used to
      increase aortic blood flow and demonstrate hemodynamic-induced changes in aortic
      valve area. These valve-area changes affect the accuracy of Doppler cardiac
      output determinations.

PMID- 11226081
TI  - An investigation of a new activated clotting time "MAX-ACT" in patients
      undergoing extracorporeal circulation.
AB  - Activated clotting time (ACT) is a test used in the operating room for monitoring
      heparin effect. However, ACT does not correlate with heparin levels because of
      its lack of specificity for heparin and its variability during hypothermia and
      hemodilution on cardiopulmonary bypass (CPB). A modified ACT using maximal
      activation of Factor XII, MAX-ACT (Actalyke MAX-ACT; Array Medical, Somerville,
      NJ), may be less variable and more closely related to heparin levels. We compared
      MAX-ACT with ACT in 27 patients undergoing CPB. We measured ACT, MAX-ACT,
      temperature, and hematocrit at six time points: baseline; postheparin; on CPB 30,
      60, and 90 min; and postprotamine. Additionally, we assessed anti-Factor Xa
      heparin activity and antithrombin III activity at four of these six time points.
      With institution of CPB and hemodilution, MAX-ACT and ACT did not change
      significantly but had a tendency to increase, whereas concomitant heparin levels
      decreased (P = 0.065). Neither test correlated with heparin levels. ACT and MAX
      ACT did not differ during normothermia but did during hypothermia, and ACT was
      significantly longer than MAX-ACT (P = 0.009). At the postheparin time point, ACT
      heparin sensitivity (defined as [ACT postheparin - ACT baseline]/[heparin
      concentration postheparin - heparin concentration baseline]) was greater than MAX
      ACT-heparin sensitivity (analogous calculation for MAX-ACT; 520 [266 - 9366] s.
      U(-1). mL(-1) vs 468 [203 - 8833] s. U(-1). mL(-1); P = 0.022). IMPLICATIONS: MAX
      ACT (a new activated clotting time [ACT] test) uses more maximal clotting
      activation in vitro and, although it is less susceptible to increase because of
      hypothermia and hemodilution than ACT, lack of correlation with heparin levels
      remains a persistent limitation.

PMID- 11226083
TI  - The protective effect of acadesine on lung ischemia-reperfusion injury.
AB  - The purine precursor acadesine is highly effective in preventing ischemia
      reperfusion (I-R) injury of the heart and intestine. The aim of this study was to
      test the effect of acadesine on I-R--induced lung injury. The lobar artery of the
      left lower lung lobe in intact-chest, spontaneously breathing cats was occluded
      for 2 h (Group 1, ischemia) and reperfused for 3 h (Group 2, I-R). Animals were
      subjected to one of the following three protocols: acadesine administered IV 15
      min before ischemia (Group 3), 15 min before reperfusion (Group 4), or 30 min
      after reperfusion (Group 5). Acadesine was administered at an initial dose of 2.5
      mg. kg(-1). min(-1) for 5 min, followed by 0.5 mg. kg(-1). min(-1) until the end
      of reperfusion. Injury was assessed by histologic examination. The right lower
      lobe served as control. Compared with the right lower lobe, which showed no
      abnormal findings in any group (percentage of injured alveoli, 2% +/- 1% to 4% +/
      2%), the left lower lung lobe in the I-R group revealed a disrupted alveolar
      structure with 63% +/- 9% injured alveoli. Ischemia alone did not produce
      alterations in alveolar structure. Acadesine significantly reduced the number of
      injured alveoli when given before ischemia (4% +/- 1%) or reperfusion (6% +/- 2%)
      but not when administered after reperfusion (62% +/- 8%). In conclusion,
      acadesine, when administered before ischemia or reperfusion, can blunt I-R
      induced lung injury. The mechanism underlying the protection remains to be
      elucidated. IMPLICATIONS: Acadesine reduces ischemia-reperfusion-induced lung
      injury in spontaneously breathing cats when administered before ischemia or
      reperfusion, but not after reperfusion.

PMID- 11226084
TI  - Predicting the risk of death from heart failure after coronary artery bypass
      graft surgery.
AB  - Heart failure is the most common cause of death among coronary artery bypass
      graft (CABG) patients. In addition, most variation in observed mortality rates
      for CABG surgery is explained by fatal heart failure. The purpose of this study
      was to develop a clinical risk assessment tool so that clinicians can rapidly and
      easily assess the risk of fatal heart failure while caring for individual
      patients. Using prospective data for 8,641 CABG patients, we used logistic
      regression analysis to predict the risk of fatal heart failure. In multivariate
      analysis, female sex, prior CABG surgery, ejection fraction <40%, urgent or
      emergency surgery, advanced age (70-79 yr and >80 yr), peripheral vascular
      disease, diabetes, dialysis-dependent renal failure and three-vessel coronary
      disease were significant predictors of fatal postoperative heart failure. A
      clinical risk assessment tool was developed from this logistic regression model,
      which had good discriminating characteristics (receiver operating characteristic
      clinical source = 0.75, 95% confidence interval: 0.71, 0.78). IMPLICATIONS: In
      contrast to previous cardiac surgical scoring systems that predicted total
      mortality, we developed a clinical risk assessment tool that evaluates risk of
      fatal heart failure. This distinction is relevant for quality improvement
      initiatives, because most of the variation in CABG mortality rates is explained
      by postoperative heart failure.

PMID- 11226085
TI  - Morphine enhances myofilament CA(2+) sensitivity in intact guinea pig beating
      hearts.
AB  - We investigated whether morphine alters intracellular Ca(2+) concentration
      ([Ca(2+)](i)), left ventricular pressure (LVP), and myofilament Ca(2+)
      sensitivity under physiologic conditions in intact guinea pig beating hearts and
      whether delta(1), delta(2), and kappa opioid stimulations are related to the
      direct cardiac effects of morphine. Transmural LV phasic [Ca(2+)](i) was measured
      from fluorescence signals at 385 nm and 456 nm. The Ca(2+) transients during each
      contraction were defined as available [Ca(2+)](i). The hearts were perfused with
      modified Krebs-Ringer solution containing morphine in the absence and presence of
      delta(1) (BNTX), delta(2) (NTB), and kappa (nor-BNI) antagonists, while developed
      LVP and available [Ca(2+)](i) were recorded. Morphine (1 microM) decreased
      available [Ca(2+)](i) by 44 +/- 12 nM without decreasing developed LVP at 2.5 mM
      of [CaCl(2)](e) (P < 0.05). Morphine (1 microM) caused a leftward shift in the
      curve of developed LVP as a function of available [Ca(2+)](i) (P < 0.05). BNTX (1
      microM), but not nor-BNI (1 microM) or NTB (0.1 microM) blocked morphine (1
      microM) effects to decrease available [Ca(2+)](i). Morphine decreases available
      [Ca(2+)](i) but not LVP, and it enhances myofilament Ca(2+) sensitivity under
      physiologic conditions at clinical concentrations in intact isolated beating
      guinea pig hearts. The delta(1) opioid stimulation modifies the effects of
      morphine on Ca(2+) transients and myofilament Ca(2+) sensitivity. IMPLICATIONS:
      Morphine modifies myofilament Ca(2+) sensitivity and Ca(2+) transients in guinea
      pig hearts at concentrations that are clinically relevant.

PMID- 11226086
TI  - A novel approach to measuring circulating blood volume: the use of a hemoglobin
      based oxygen carrier in a rabbit model.
AB  - Hemoglobin-based oxygen carriers (HBOC) may be ideal for monitoring circulating
      plasma volume (CV-P) and circulating blood volume (CV-B). We used an HBOC
      (Hemoglobin glutamer-200 [bovine], Oxyglobin; Biopure, Cambridge, MA) as an
      indicator for relative CV-B in the rabbit model. Accuracy of the technique was
      determined by comparison with the Evans blue dye (EBD) dilution technique in 19
      anesthetized female New Zealand rabbits weighing 2.0 to 10.6 kg. The measurements
      were performed at baseline, after hemorrhage (1/3 of CV-B), normovolemic
      hemodilution (replacement of 1/3 CV-B by Hextend; Abbot Laboratories, North
      Chicago, IL), and hypervolemic hemodilution (additional infusion of Hextend(R) in
      a volume equal to 1/3 of CV-B). Hemoglobin concentration was measured by using a
      HemoCue photometer (HemoCue AB, Angelholm, Sweden). EBD concentration was
      analyzed by using linear regression to estimate Time 0 concentration; Time 0 was
      defined as EBD injection time. The difference between CV-P values determined by
      EBD and HBOC dilution was independent from the magnitude of the CV-P value. The
      relative bias was 1.29 mL, and the precision (one SD) was 2.82 mL. The difference
      did not reach statistical significance. IMPLICATIONS: Circulating plasma and
      blood volumes can be accurately estimated by plasma hemoglobin concentration
      measurements by using hemoglobin-based oxygen carrier infusion.

PMID- 11226087
TI  - Allosteric modification of oxygen delivery by hemoglobin.
AB  - Hemoglobin affinity for oxygen is altered by pH, temperature, and high altitude,
      making oxygen more readily available to the tissues. RSR13 (Allos Therapeutics,
      Denver, CO), an analog of the drugs clofibrate and bezofibrate, causes a dose
      dependent, rightward shift of the oxygen dissociation curve in animals and
      humans. We tested the safety, pharmacodynamic, and pharmacokinetics of RSR13, an
      allosteric modifier of hemoglobin, in patients having general surgery in a
      prospective, randomized, double-blinded, placebo-controlled, dose-escalation
      clinical trial. After the induction of general anesthesia with endotracheal
      intubation, 26 patients who consented were randomly assigned to receive an
      infusion of RSR13 or placebo (2:1) in an ascending dose scheme. Doses studied
      were 10, 20, 30, 40, 50, 60, 75, and 100 mg/kg infused for 30--60 minutes.
      Samples were taken for determination of RSR13 concentration in plasma, red blood
      cells, and urine, as well as for determination of the p50 in blood by using three
      point tonometry at frequent intervals after the infusion of the study drug. The
      RSR13 administration resulted in a dose-dependent rightward shift of the oxygen
      dissociation curve, with the target p50 shift of 10 mm Hg achieved at the 75- and
      100-mg/kg doses. No differences were seen between RSR13 and placebo groups in
      laboratory or hemodynamic findings, with the exception of a transient, limited
      increase in serum creatinine in 3 patients who received RSR13. These increases
      peaked at 48 h (2.2, 3.5, and 4.5 mg/dL respectively), were not associated with
      oliguria, did not require treatment, and did not prolong hospitalization in any
      patient. The reasons for the unexplained increases in serum creatinine were not
      evident, but potentially included surgery itself (nephrectomy), patient
      condition, or the concomitant administration of renally cleared medications or
      drugs that affect renal blood flow. IMPLICATIONS: We studied the safety and
      tolerance of an investigational drug, RSR13 (Allos Therapeutics, Denver, CO), in
      general surgery patients. This drug, which increases the amount of oxygen
      available to the body, was well tolerated by the 17 patients who received it.
      There were clinically relevant increases in serum creatinine in 3 patients,
      indicating a decrease in renal function, but these increases were short-lived and
      resolved without treatment.

PMID- 11226088
TI  - The effect of anxiety and personality on the pharmacokinetics of oral midazolam.
AB  - We investigated the relationship between the pharmacokinetic variables of oral
      midazolam and patients' state/trait anxiety and personality. Twenty-six patients
      received the standard 15-mg oral dose for anxiolysis on the evening before
      otorhinolaryngological surgery. Blood samples were taken over a 9-h period after
      the administration, and the samples were analyzed for concentrations of midazolam
      and its two main metabolites by using a gas chromatography-mass spectrometry
      procedure. The pharmacokinetic variables maximum concentration, time to reach the
      maximum concentration, the elimination half-life, and the area under the curve
      were calculated from these data. When the patients were divided into groups with
      respect to their anxiety and personality scores, no significant differences in
      the pharmacokinetic variables of midazolam could be found. Only small,
      insignificant changes in the maximum concentrations were found with respect to
      nervousness and emotionality. We conclude that personality traits and anxiety
      levels had no effect on the pharmacokinetic variables of midazolam. IMPLICATIONS:
      We conclude that personality traits and anxiety levels had no effect on the
      pharmacokinetic variables of midazolam. Therefore, it is not necessary to obtain
      anxiety or personality scores to find the proper midazolam dose for the
      individual patient.

PMID- 11226089
TI  - Intraarticular sufentanil administration facilitates recovery after day-case knee
      arthroscopy.
AB  - We evaluated the efficacy of intraarticular sufentanil in the prevention of
      postoperative pain after day-case arthroscopic procedures. Sixty patients were
      randomly assigned to receive either intraarticular sufentanil, 5 or 10 microg,
      and saline IV, or intraarticular saline and sufentanil 5 microg IV (control). All
      study medication was administered in a double-blinded fashion. Postoperatively
      and the day after surgery, pain levels at rest and during movement (i.e., active
      flexion of the knee), measured by a visual analog scale, were significantly lower
      in the Sufentanil groups compared with the Control group. Moreover,
      intraarticular sufentanil significantly reduced the postoperative consumption of
      analgesics. The time until discharge from the postanesthesia care unit (assessed
      by the Aldrete score) was significantly shorter in the patients receiving
      sufentanil intraarticularly. There were no significant differences between the
      two Sufentanil groups either in the intensity of postoperative pain or in
      discharge times from the postanesthesia care unit. We conclude that
      intraarticular sufentanil in arthroscopic knee procedures is a simple, effective,
      safe and well-tolerated analgesic technique for outpatients undergoing
      arthroscopic procedures. Increasing the dose sufentanil from 5 to 10 microg
      intraarticularly offered no additional advantage. Intraarticular sufentanil (5-10
      microg) administration improves postoperative management after day-case
      diagnostic arthroscopic knee procedures. IMPLICATIONS: Intraarticular sufentanil
      (5-10 microg) administration improves postoperative management after day-case
      diagnostic arthroscopic knee procedures.

PMID- 11226090
TI  - The use of transcutaneous acupoint electrical stimulation for preventing nausea
      and vomiting after laparoscopic surgery.
AB  - Nonpharmacologic techniques may be effective in preventing postoperative nausea
      and vomiting (PONV). This sham-controlled, double-blinded study was designed to
      examine the antiemetic efficacy of transcutaneous acupoint electrical stimulation
      (TAES) in a surgical population at high risk of developing PONV. We studied 221
      outpatients undergoing laparoscopic cholecystectomy with a standardized general
      anesthetic technique in this randomized, multicenter trial. In the TAES group, an
      active ReliefBand(Woodside Biomedical, Inc., Carlsbad, CA) device was placed at
      the P6 acupoint, whereas in the Sham and Placebo groups, an inactive device was
      applied at the P6 acupoint and at the dorsal aspect of the wrist, respectively.
      The ReliefBand was applied after completion of electrocautery and remained in
      place for 9 h after surgery. The incidence of PONV and need for "rescue"
      medication were evaluated at predetermined time intervals. TAES was associated
      with a significantly decreased incidence of moderate-to-severe nausea as denoted
      on the Functional Living Index-Emesis score for up to 9 h after surgery (5%-11%
      for the TAES group vs 16%-38% [P < 0.05] and 15%-26% [P < 0.05] for Sham and
      Placebo groups, respectively). TAES was also associated with a larger proportion
      of patients free from moderate to severe nausea symptoms (73% vs 41% and 49% for
      Sham and Placebo groups, respectively; P < 0.05). However, there were no
      statistically significant differences among the three groups with regard to
      incidence of vomiting or the need for rescue antiemetic drugs. We conclude that
      TAES with the ReliefBand at the P6 acupoint reduces nausea, but not vomiting,
      after laparoscopic cholecystectomy. IMPLICATIONS: Transcutaneous acupoint
      electrical stimulation at the P6 acupoint reduced postoperative nausea, but not
      vomiting, in outpatients undergoing laparoscopic cholecystectomy procedures.

PMID- 11226091
TI  - The effect of dexamethasone on postoperative vomiting after tonsillectomy.
AB  - In this double-blinded, randomized, placebo-controlled study, we assessed the
      effect of dexamethasone 0.5 mg/kg IV administered preoperatively in 110 children
      2-12 yr old, undergoing electrodissection adenotonsillectomy, using a
      standardized anesthetic technique. The incidence of early and late vomiting, the
      time to first oral intake, the quality of oral intake, the satisfaction scores,
      and the duration of IV hydration were compared in both groups. The overall
      incidence of vomiting, as well as the incidence of late vomiting, was
      significantly less in the Dexamethasone group as compared with the Saline group
      (23% and 19% vs 51% and 34%, respectively). The time to first oral intake and the
      duration of IV hydration were shorter in the Dexamethasone group compared with
      the Saline group (P < 0.05). The quality of oral intake and the satisfaction
      scores were better in the Dexamethasone group than in the Saline group (P <
      0.05). This report confirms the beneficial effect of IV dexamethasone on both
      vomiting and oral intake in children undergoing electrodissection
      adenotonsillectomy. IMPLICATIONS: In this double-blinded, placebo-controlled
      study, we examined the efficacy of a single dose of dexamethasone 0.5 mg/kg IV on
      posttonsillectomy vomiting and oral intake in children 2-12 yr old. Dexamethasone
      significantly decreased the incidence of postoperative vomiting during the first
      24 h, shortened the time to the first oral intake and the duration of IV
      hydration, and improved the quality of oral intake and the satisfaction scores of
      the patients.

PMID- 11226092
TI  - The release of antidiuretic hormone is appropriate in response to hypovolemia
      and/or sodium administration in children with severe head injury: a trial of
      lactated Ringer's solution versus hypertonic saline.
AB  - We conducted an open, randomized, and prospective study to determine the effect
      of hypertonic saline on the secretion of antidiuretic hormone (ADH) and
      aldosterone in children with severe head injury (Glasgow coma scale <8). Thirty
      one consecutive patients at a level III pediatric intensive care unit at a
      children's hospital received either lactated Ringer's solution (Ringer's group, n
      = 16) or hypertonic saline (Hypertonic Saline group, n = 15) over a 3-day period.
      Serum ADH levels were significantly larger in the Hypertonic Saline group as
      compared with the Ringer's group (P = 0.001; analysis of variance) and were
      correlated to sodium intake (Ringer's group: r = 0.39, R(2) = 0.15, P = 0.02;
      Hypertonic Saline group: r = 0.42, R(2) = 0.18, P = 0.02) and volume of fluids
      given IV (Ringer's group: r = 0.38, R(2) = 0.15, P = 0.02; Hypertonic Saline
      group: r = 0.32, R(2) = 0.1, P = not significant). Correlation of ADH to plasma
      osmolality was significant if plasma osmolality was >280 mOsm/kg (r = 0.5, R(2) =
      0.25, P = 0.06), indicating an osmotic threshold for ADH release. Serum
      aldosterone levels were larger on the first day than during Days 2 and 3 in both
      groups and inversely correlated to serum sodium levels only in the Ringer's group
      (r = -0.55, R(2) = 0.3, P < 0.001). This group received a significantly larger
      fluid volume on Day 1 (P = 0.05, Mann-Whitney U-test) than did patients in the
      Hypertonic Saline group, indicating hypovolemia during the first day. Head
      injured children have appropriate levels of ADH. They may be hypovolemic during
      the first day of treatment, especially if they receive lactated Ringer's
      solution. IMPLICATIONS: In head-injured patients, we recommend fluid restriction
      to avoid inappropriate secretion of antidiuretic hormone. In a prospective,
      randomized, and controlled study in 31 children, we were able to show that the
      antidiuretic hormone levels are appropriate in response to hypovolemia, sodium
      load, or both.

PMID- 11226093
TI  - Postoperative coma in a child with carnitine palmitoyltransferase I deficiency.
AB  - IMPLICATIONS: We describe prolonged drowsiness proceeding to hepatic
      encephalopathy in a child with sickle cell trait and carnitine
      palmitoyltransferase deficiency. The latter defect of fatty acid metabolism is
      associated with striated muscle dysfunction and hepatic failure.

PMID- 11226094
TI  - Severe anaphylactic reaction to cisatracurium in a child.

PMID- 11226095
TI  - The effects of low-flow sevoflurane and isoflurane anesthesia on renal function
      in patients with stable moderate renal insufficiency.
AB  - Sevoflurane degrades to Compound A, which is nephrotoxic in rats. Therefore, the
      renal effects of Compound A is an area of intense debate. We investigated the
      effects of low-flow sevoflurane and isoflurane anesthesia on renal function in
      patients with stable renal insufficiency. Seventeen patients with a serum
      creatinine level of more than 1.5 mg/dL were anesthetized with sevoflurane or
      isoflurane at a total flow of 1 L/min. Serum creatinine and blood urea nitrogen
      were measured before anesthesia and again 1, 2, 3, 5, 7, and 14 days after
      anesthesia. The 24-h creatinine clearance was measured before anesthesia and 7
      days after anesthesia. There were no significant differences in the blood urea
      nitrogen levels, serum creatinine concentrations, or creatinine clearance before
      and after anesthesia within each group. These results suggest that sevoflurane
      and isoflurane have similar effects on renal function in patients with moderately
      impaired renal function. Further study of the effects of low-flow sevoflurane
      anesthesia on impaired renal function with a larger sample size than ours is
      required to resolve the issue of sevoflurane safety in patients with renal
      insufficiency. IMPLICATIONS: The serum creatinine and blood urea nitrogen data
      indicate that, for exposures of <130 ppm/h in Compound A inspired area under the
      curve, renal effects of low-flow sevoflurane are similar to those of isoflurane
      in patients with stable renal insufficiency.

PMID- 11226096
TI  - The determinants of propofol induction of anesthesia dose.
AB  - Recently it was reported that the pharmacokinetics of propofol are modified by
      changes in cardiac output. The objective of this study was to evaluate the
      effects of cardiac output and other factors on the hypnotic dose of propofol. One
      hundred surgical patients were administered indocyanine green immediately before
      the induction of anesthesia to measure their cardiac outputs and blood volumes.
      Propofol (250 microg. kg(-1). min(-1)) was infused IV for 8 min, and the hypnotic
      dose of propofol and the time to hypnosis were recorded. The plasma concentration
      of propofol immediately after 2 mg/kg infusion was measured. Multiple regression
      analysis showed that, in addition to age and weight, cardiac output was a small
      but significant factor for predicting the hypnotic dose of propofol (R(2) =
      0.468, P < 0.001), the time to hypnosis (R(2) = 0.454, P < 0.001), and the plasma
      concentration of propofol (R(2) = 0.248, P < 0.01). Cardiac output, age, and
      weight showed similar partial coefficients for the hypnotic dose (0.128, 0.137,
      and 0.140, respectively). IMPLICATIONS: This study demonstrates a significant
      relationship between cardiac output and the hypnotic dose of propofol. We suggest
      that anesthesiologists should include cardiac output, as well as age and weight,
      in calculating the induction dose of propofol.

PMID- 11226097
TI  - Intraoperative monitoring of the recurrent laryngeal nerve during single-lung
      ventilation in esophagectomy.
AB  - IMPLICATIONS: We describe the use of a surface electrode attached to a double
      lumen endobronchial tube to identify and monitor the recurrent laryngeal nerve
      during esophagectomy in single-lung ventilation. The technique is demonstrated in
      the case of a patient with carcinoma of the distal esophagus.

PMID- 11226098
TI  - The addition of morphine prolongs fentanyl-bupivacaine spinal analgesia for the
      relief of labor pain.
AB  - The combination intrathecal fentanyl (25 microg) and bupivacaine (2.5 mg)
      provides effective labor analgesia for approximately 90 minutes. The purpose of
      this prospective, randomized, double-blinded investigation was to determine if
      the addition of morphine (150 microg) to the intrathecal combination of fentanyl
      (25 microg) and bupivacaine (2.5 mg) would prolong labor analgesia. By using the
      combined spinal epidural technique, 95 healthy primiparous laboring women in
      early labor received 2 mL of one of the two intrathecal study solutions, either
      FB (n = 48): fentanyl (25 microg) and bupivacaine (2.5 mg); or FBM (n = 47):
      fentanyl (25 microg) and bupivacaine (2.5 mg) plus morphine (150 microg). The
      mean duration of labor analgesia was significantly longer in the FBM group than
      in the FB group (252 +/- 63 min vs 148 +/- 44 min, P < 0.01). There were no
      significant differences between the two groups regarding the sensory levels, the
      incidence of nausea, vomiting, pruritus, hypotension, or operative delivery. In
      conclusion, the addition of 150 microg of morphine to the intrathecal combination
      of fentanyl plus bupivacaine prolonged the duration of labor analgesia duration
      without increasing adverse effects. IMPLICATIONS: The addition of morphine (150
      microg) to intrathecal fentanyl (25 microg) and bupivacaine (2.5 mg) prolongs the
      duration of labor analgesia duration without increasing adverse effects.

PMID- 11226099
TI  - The effect of treatment with albumin, hetastarch, or hypertonic saline on
      neurological status and brain edema in a rat model of closed head trauma combined
      with uncontrolled hemorrhage and concurrent resuscitation in rats.
AB  - In rats subjected to closed head trauma (CHT) plus uncontrolled hemorrhage,
      giving 0.3 mL of 0.9% saline per 0.1 mL of blood lost did not restore mean
      arterial blood pressure (MAP) or improve neurological severity score (NSS). In
      CHT without hemorrhage, giving 20% albumin or 10% hetastarch improved NSS. We
      hypothesized that these latter treatments would also improve NSS after CHT plus
      uncontrolled hemorrhage. Rats were randomly assigned to one of seven groups.
      Experimental conditions were CHT (yes or no), uncontrolled hemorrhage (yes or
      no), and fluid given to replace blood loss (none; 10% hetastarch, 20% albumin, or
      3% saline [0.1 mL per 0.1 mL of blood lost]; or 0.9% saline [0.3 mL per 0.1 mL of
      blood lost]). NSS (0--25 scale, where 0 = no impairment) was determined at 1, 4,
      and 24 h, and brain water content was determined at 24 h after CHT. NSS (median
      +/- range) at 24 h was 11 +/- 6 when no fluid was given; 16 +/- 5 with 10%
      hetastarch; 14 +/- 5 with 20% albumin; 12 +/- 4 with 3% saline; and 13 +/- 4 with
      0.9% saline given (not significant). In addition, brain water content and MAP did
      not differ among the groups receiving CHT with or without uncontrolled
      hemorrhage. In our model of CHT plus uncontrolled hemorrhage in rats, giving 10%
      hetastarch, 20% albumin, 3% saline, or 0.9% saline failed to improve NSS, brain
      water content, or MAP. IMPLICATIONS: In previous studies of closed head trauma
      (CHT) without hemorrhage, giving 20% albumin or 10% hetastarch improved
      neurological severity scores (NSSs). We hypothesized that these treatments also
      might be beneficial in CHT plus uncontrolled hemorrhage. We found that giving 10%
      hetastarch, 20% albumin, 3% saline, or 0.9% saline failed to improve NSS, brain
      water content, or mean arterial blood pressure.

PMID- 11226100
TI  - The effects of olprinone (a phosphodiesterase III inhibitor) on hepatic vascular
      bed in a porcine model of endotoxemia.
AB  - Decreased hepatic blood flow, and impaired hepatic oxygen delivery caused by
      endotoxin, result in hepatic metabolic deterioration followed by liver
      dysfunction and multiple organ failure. Among phosphodiesterase III inhibitors,
      only olprinone increases hepatosplanchnic blood flow. We evaluated the effects of
      olprinone on systemic hemodynamics, hepatic circulation, and hepatic oxygen
      delivery in a porcine model of endotoxemia. Fifteen pigs received a continuous
      infusion (1.7 microg. kg(-1). h(-1)) of endotoxin (lipopolysaccharide [LPS]) via
      the portal vein for 240 min. Seven of these pigs received olprinone infusion (0.3
      microg. kg(-1). min(-1)) via a central vein from t = 150 min to t = 240 min,
      whereas the eight remaining pigs served as LPS controls. Continuous infusion of
      LPS caused significant reductions in hemodynamic variables and a significant
      increase in arterial lactate. After the administration of olprinone during the
      LPS infusion, portal venous flow and hepatic oxygen delivery were increased and
      were higher than in the LPS group. Furthermore, olprinone prevented any further
      increase in arterial lactate. We conclude that the administration of olprinone
      halted the disturbances in the hepatic circulation, especially in portal venous
      flow and hepatic oxygen delivery, in a porcine model of endotoxemia.
      IMPLICATIONS: Endotoxin is a causative factor in peripheral vascular failure,
      resulting in a hemodynamic depression that includes a reduction in liver blood
      flow. The administration of olprinone (phosphodiesterase III inhibitor) improves
      the liver blood flow circulation in a porcine model of endotoxemia.

PMID- 11226101
TI  - Selective iNOS inhibition prevents hypotension in septic rats while preserving
      endothelium-dependent vasodilation.
AB  - Nitric oxide (NO) derived from inducible nitric oxide synthase (iNOS) mediates
      hypotension and metabolic derangements in sepsis. We hypothesized that selective
      iNOS-inhibition would prevent hypotension in septic rats without inhibiting
      endothelium-dependent vasodilation caused by the physiologically important
      endothelial NOS. Rats were exposed to lipopolysaccharide (LPS) for 6 h and the
      selective iNOS-inhibitor L-N6-(1-iminoethyl)-lysine (L-NIL), the nonselective NOS
      inhibitor N:(G)-nitro-L-arginine methyl ester (L-NAME), or control. Mean arterial
      pressure (MAP) and vasodilation to acetylcholine (ACh, endothelium-dependent),
      sodium nitroprusside (SNP, endothelium-independent), and isoproterenol (ISO,
      endothelium-independent beta agonist) were determined. Exhaled NO,
      nitrate/nitrite-(NOx) levels, metabolic data, and immunohistochemical staining
      for nitrotyrosine, a tracer of peroxynitrite-formation were also determined. In
      control rats, L-NAME increased MAP, decreased the response to ACh, and increased
      the response to SNP, whereas L-NIL did not alter these variables. LPS decreased
      MAP by 18% +/- 1%, decreased vasodilation (ACh, SNP, and ISO), increased exhaled
      NO, NOx, nitrotyrosine staining, and caused acidosis and hypoglycemia. L-NIL
      restored MAP and vasodilation (ACh, SNP, and ISO) to baseline and prevented the
      changes in exhaled NO, NOx, pH, and glucose levels. In contrast, L-NAME restored
      MAP and SNP vasodilation, but did not alter the decreased response to ACh and ISO
      or prevent the changes in exhaled NO and glucose levels. Finally, L-NIL but not L
      NAME decreased nitrotyrosine staining in LPS rats. In conclusion, L-NIL prevents
      hypotension and metabolic derangements in septic rats without affecting
      endothelium-dependent vasodilation whereas L-NAME does not. IMPLICATIONS: Sepsis
      causes hypotension and metabolic derangements partly because of increased nitric
      oxide. Selective inhibition of nitric oxide produced by the inducible nitric
      oxide synthase enzyme prevents hypotension and attenuates metabolic derangements
      while preserving the important vascular function associated with endothelium
      dependent vasodilation in septic rats.

PMID- 11226102
TI  - A case of fatal paradoxical fat embolism syndrome detected by intraoperative
      transesophageal echocardiography.

PMID- 11226103
TI  - Survival after failed intraoperative resuscitation: a case of "Lazarus syndrome".

PMID- 11226104
TI  - Cost identification analysis for succinylcholine.
AB  - The cost of a dose of succinylcholine from society's perspective equals the
      acquisition cost of the drug plus the cost of its adverse outcomes. We
      hypothesized that although the acquisition cost of succinylcholine is minimal,
      the true cost would be much larger. We reviewed the medical literature to
      identify the total cost of a dose of succinylcholine when administered for
      nonemergency purposes according to manufacturers' guidelines (i.e., to adults
      only). We found that 88% of the cost per dose of succinylcholine was for the
      chance of dying or sustaining permanent brain injury from anaphylactic or
      anaphylactoid reactions to succinylcholine. Consequently, the estimated cost per
      dose of succinylcholine was sensitive to the incidence of anaphylactic or
      anaphylactoid reactions to succinylcholine, the risk of severe injury from
      anaphylactic or anaphylactoid reactions, and the financial value of unforeseen
      instant death or permanent brain injury. The range for the cost per dose of
      succinylcholine was thus large, $9 to $93. Our best estimate of the cost per dose
      was $37. We conclude that the true cost per dose of succinylcholine from
      society's perspective is more than 20 times the acquisition cost. However, a
      precise costing requires better knowledge of the incidence and consequences of
      anaphylactic or anaphylactoid reactions to succinylcholine. IMPLICATIONS: The
      true cost of succinylcholine is more than 20 times the acquisition cost of the
      drug. The estimated cost is very sensitive to the risk and cost of patients dying
      or sustaining brain injury from anaphylactic or anaphylactoid reactions to
      succinylcholine.

PMID- 11226105
TI  - Examining the evidence in anesthesia literature: a critical appraisal of
      systematic reviews.
AB  - Systematic reviews are structured reviews that use scientific strategies to
      reduce bias in the collection, appraisal, and interpretation of relevant studies.
      We undertook a systematic review of published systematic reviews in perioperative
      medicine to summarize the areas currently covered by this type of literature, to
      evaluate the quality of systematic reviews in this field, and to assess some of
      the methodologic and reporting issues that are unique to systematic reviews.
      Computerized bibliographic databases, citation review, and hand searches were
      performed to identify eligible articles. Quality was assessed using the Overview
      Quality Assessment Questionnaire. Eight-two systematic reviews were found.
      Reviews in perioperative medicine tended to evaluate prophylactic or therapeutic
      interventions. No differences were seen in quality between reviews published in
      anesthesia and nonanesthesia journals. Nearly half of all systematic reviews had
      only minor or minimal flaws; however, methods can be improved with expanded
      search strategies, use of least two reviewers to assess each study, use of
      validated methods to evaluate quality, and assessment of potential sources of
      bias. IMPLICATIONS: The quality of systematic reviews relating to perioperative
      medicine was examined systematically and found to be similar in quality to those
      in other specialties. Adoption of recently published criteria on writing and
      methods could further improve this type of literature.

PMID- 11226106
TI  - The effects of lactated Ringer's solution infusion on cardiac output changes
      after spinal anesthesia.
AB  - We evaluated the effects of an infusion of lactated Ringer's (LR) solution on
      changes in cardiac output (CO) after spinal anesthesia. Seventy-five patients
      scheduled for lower extremity surgery under spinal anesthesia were studied. We
      measured CO (impedance cardiography method) and blood pressure for 25 min before
      and 30 min after spinal anesthesia. Patients were randomly assigned to three
      groups. In the No Infusion group, no LR solution was given during the period of
      measurements. The LR Before group received 12 mL/kg of LR solution within 20 min
      before spinal anesthesia. The LR After group received 12 mL/kg of LR solution
      within 20 min starting immediately after spinal anesthesia. After spinal
      anesthesia, CO decreased by 13.9% in the No Infusion group. In the LR Before
      group, CO increased after the infusion by 20% and returned to baseline value 30
      min after spinal anesthesia. In the LR After group, CO increased after spinal
      anesthesia, and 30 min after spinal anesthesia, CO was 11.3% above baseline. We
      conclude that the decrease in CO after spinal anesthesia can be prevented by the
      infusion of an LR solution, with CO reaching the highest value while the infusion
      is running. IMPLICATIONS: We studied the effects of lactated Ringer's solution
      infusion on cardiac output changes after spinal anesthesia. If the patients
      received no infusion, cardiac output decreased after spinal anesthesia. However,
      if the patients received lactated Ringer's solution infusion, cardiac output was
      maintained.

PMID- 11226107
TI  - A comparison of two constant-dose continuous infusions of remifentanil for severe
      postoperative pain.
AB  - We evaluated the analgesic efficacy and safety of two continuous constant-dose
      infusions of IV remifentanil, without infusion rate increments or the addition of
      boluses, in patients with severe postoperative pain during the first 4 h after
      general anesthesia with IV propofol-remifentanil. Thirty patients were randomly
      assigned to two groups of 15 subjects each according to the remifentanil dose
      administered: 0.1 microg. kg(-1). min(-1) IV (Group A) or 0.05 microg. kg(-1).
      min(-1) IV (Group B). Rescue analgesia was provided with meperidine (0.5 mg/kg
      IV) when pain intensity on the simple verbal scale (SVS) > or =2. The criteria
      for adequate analgesia (SVS 0-1, respiratory frequency >8/min. and SpO(2) >90%)
      after 4 h were met by 78% and 75% of the patients in Groups A and B, respectively
      (P = ns). "Meperidine rescue" analgesia was significantly more in Group B (26%)
      than in Group A (6%) (P < 0.05). There were no cases of respiratory depression,
      and nausea and emesis occurred in one patient in each group (6.5%). We conclude
      that IV remifentanil is an effective and safe opioid for the treatment of
      postoperative pain at a constant dose of 0.1 microg. kg(-1). min(-1) with a need
      for rescue analgesia 4 times less than a constant dose of 0.05 microg. kg(-1).
      min(-1). IMPLICATIONS: Our study suggests that the use of a constant continuous
      infusion of remifentanil 0.1 microg.kg(-1).min(-1)IV is an effective alternative
      in the treatment of severe postoperative pain.

PMID- 11226108
TI  - A comparison of ropivacaine and bupivacaine for cervical plexus block.
AB  - We compared bupivacaine 0.5% and ropivacaine 0.75% for cervical plexus block
      (CB). Forty patients scheduled for carotid artery surgery were allocated randomly
      to undergo superficial and deep CB with 30 mL of one of the two anesthetic
      solutions. We evaluated the onset of anesthetic block; the requirement for
      supplementation during the surgery; the patients' satisfaction; postoperative
      pain on a visual analog scale at 1, 2, and 3 h; and the use of paracetamol as a
      rescue analgesic medication. Arterial blood was sampled immediately and 1, 3, 5,
      10, 15, 30, 45, and 60 min after CB for measurements of bupivacaine or
      ropivacaine concentrations. Patients in both groups had equivalent onset of CB,
      local infiltration with lidocaine during surgery, and satisfaction scores. In the
      Bupivacaine group, visual analog scale scores were lower at 2 and 3 h, and the
      delay before paracetamol administration was prolonged. Observed peak
      concentrations were larger in the Ropivacaine group (4.25 [2.07-6.59 mg/L] vs
      3.02 [0.98-5.82 mg/L]), but time to reach peak concentrations was comparable (5
      [1-15 min] vs 5 [0-45 min] in the Ropivacaine and Bupivacaine groups,
      respectively). We conclude that ropivacaine has no advantage over bupivacaine for
      CB. IMPLICATIONS: Compared with bupivacaine (150 mg), a larger dose of
      ropivacaine (225 mg) produces comparable features of cervical plexus block but
      less postoperative analgesia and larger plasma concentrations. There is no reason
      to favor ropivacaine in such a case.

PMID- 11226109
TI  - The analgesic interaction between intrathecal clonidine and glutamate receptor
      antagonists on thermal and formalin-induced pain in rats.
AB  - Clonidine, an alpha(2) adrenergic receptor agonist, inhibits glutamate release
      from the spinal cord. We studied the interaction of intrathecally administered
      clonidine and glutamate receptor antagonists on acute thermal or formalin induced
      nociception. Sprague-Dawley rats with lumbar intrathecal catheters were tested
      for their tail withdrawal response by the tail flick test and paw flinches
      produced by formalin injection after intrathecal administration of saline,
      clonidine, AP-5 (a N-methyl-D-aspartate receptor antagonist), or YM872 (an alpha
      amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist). The
      combinations of clonidine and the other two agents were also tested by
      isobolographic analyses. Motor disturbance and behavioral changes were observed
      as side effects. The ED(50) values of clonidine decreased from 0.26 microg (tail
      flick), 0.12 microg (Phase 1) and 0.13 microg (Phase 2) to 0.036 microg, 0.006
      microg, and 0.013 microg with AP-5, and 0.039 microg, 0.057 microg, and 0.133
      microg with YM872, respectively. Side effects were attenuated in both
      combinations. In conclusion, spinally administered clonidine and AP-5 or YM872
      exhibited potent synergistic analgesia on acute thermal and formalin-induced
      nociception with decreased side effects in rats. IMPLICATIONS: Combinations of a
      spinally administered alpha(2) adrenergic receptor agonist and an a N-methyl-D
      aspartate receptor antagonist or an alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid receptor antagonist exhibited potent synergistic analgesia in
      acute thermal and inflammatory-induced nociception with decreased side effects.

PMID- 11226110
TI  - Antinociceptive interaction between spinal clonidine and lidocaine in the rat
      formalin test: an isobolographic analysis.
AB  - Clinical and basic science studies suggest that spinal alpha-2-adrenergic
      receptor agonists and local anesthetics produce analgesia, but interaction
      between alpha-2-adrenergic receptor agonists and local anesthetics in the
      persistent pain model has not been examined. In the present study, using
      isobolographic analysis, we investigated the antinociceptive interaction of
      intrathecal clonidine and lidocaine in the rat formalin test. Sprague-Dawley rats
      were implanted with chronic lumbar intrathecal catheters, and were tested for paw
      flinch by formalin injection. Biphasic painful behavior was counted. Intrathecal
      clonidine (3-12 nmol) was administered 15 min before formalin, and intrathecal
      lidocaine (375-1850 nmol) was administered 5 min before formalin. To examine the
      interaction of intrathecal clonidine and lidocaine, an isobolographic design was
      used. Spinal administration of clonidine produced dose-dependent suppression of
      the biphasic responses in the formalin test. Spinal lidocaine resulted in dose
      dependent transient motor dysfunction and the motor dysfunction recovered to
      normal at 10-15 min after administration. Spinal lidocaine produced dose
      dependent suppression of phase-2 activity in the formalin test. Isobolographic
      analysis showed that the combination of intrathecal clonidine and lidocaine
      synergistically reduced Phase-2 activity. We conclude that intrathecal clonidine
      synergistically interacts with lidocaine in reducing the nociceptive response in
      the formalin test. IMPLICATIONS: Preformalin administration of intrathecal
      clonidine and lidocaine dose-dependently produced antinociception in the formalin
      test. The combination of clonidine and lidocaine, synergistically produced
      suppression of nociceptive response in the persistent pain model.

PMID- 11226111
TI  - The effect of the preemptive use of the NMDA receptor antagonist dextromethorphan
      on postoperative analgesic requirements.
AB  - Both central sensitization after peripheral tissue injury and the development of
      opiate tolerance involve activation of N-methyl-D-aspartate receptors. In this
      double-blinded, randomized study, we investigated the preemptive versus
      postincisional effects of dextromethorphan, an N-methyl-D-aspartate receptor
      antagonist, on postoperative pain management. Sixty ASA I and II patients
      undergoing elective upper abdominal surgery were randomly allocated to three
      equally sized groups. The Preincisional group patients received dextromethorphan
      (120 mg) IM 30 min before skin incision and a placebo (isotonic saline) 30 min
      before the end of surgery. The Postincisional group received the same dose of
      dextromethorphan 30 min before the end of surgery and a placebo 30 min before
      skin incision, and the Control group received a placebo both 30 min before skin
      incision and 30 min before the end of surgery. A standard general anesthetic
      technique including fentanyl, propofol, isoflurane, and atracurium was used.
      Postoperative meperidine patient-controlled analgesia (PCA) was used. There were
      no significant group differences in the median pain scores except in the visual
      analog scale at 6 h both at rest and on movement; these were significantly lower
      in the Preincisional group than the other two groups (P < 0.05). The mean time to
      initiation of PCA was significantly longer in the Preincisional than in the
      Postincisional and Control groups (mean [SD]: 10.7 [2.2 h], 5.4 [2.1 h], and 3.7
      [1.6 h], respectively; P < 0.001]. The 24-h PCA-meperidine consumption was
      significantly less in the Preincisional than in the Postincisional and Control
      groups (mean [SD]: 140 [60 mg], 390 [80 mg], and 570 [70 mg], respectively; P <
      0.001]. The incidence of postoperative hypoxemia (SpO(2) < 90%) and nausea was
      significantly less in the Preincisional group (P < 0.05). In conclusion,
      preincisional IM 120 mg dextromethorphan compared with the same postincisional
      dose significantly reduced postoperative meperidine consumption. IMPLICATIONS: IM
      administration of preincisional dextromethorphan (120 mg), allowing the use of a
      larger dose sufficient to block the central sensitization caused by activation of
      the N-methyl-D-aspartate receptors, provides preemptive analgesia and has a
      supportive role in postoperative pain relief, as shown by a significant decrease
      in 24-h meperidine consumption.

PMID- 11226112
TI  - Dexamethasone for preventing nausea and vomiting associated with epidural
      morphine: a dose-ranging study.
AB  - We conducted a dose-ranging study of dexamethasone for preventing nausea and
      vomiting within the first 24 h after the administration of epidural morphine. Two
      hundred twenty-five women (n = 45 in each of the five groups) undergoing simple
      abdominal total hysterectomy under epidural anesthesia were enrolled in this
      randomized, double-blind, placebo-controlled study. When the incision closure was
      completed, patients received IV dexamethasone, 10 mg, 5 mg, or 2.5 mg; IV
      droperidol 1.25 mg; or saline 2 mL. All patients received epidural morphine 3 mg
      for postoperative analgesia. We found that patients who received dexamethasone 5
      mg or 10 mg or droperidol 1.25 mg were significantly different from those who
      received saline alone in the following variables: the total incidence of nausea
      and vomiting, the incidence of more than four vomiting episodes, the number of
      patients requiring rescue antiemetics, the total number of patients with no
      vomiting and/or no antiemetic medication (P < 0.05 to P < 0.01). The differences
      among dexamethasone 10 mg and 5 mg and droperidol 1.25 mg were not significant.
      Dexamethasone 2.5 mg was ineffective. In conclusion, because dexamethasone 5 mg
      was as effective as 10 mg as an antiemetic, we recommend the smaller dose for
      preventing nausea and vomiting associated with epidural morphine. IMPLICATIONS:
      We conducted a dose-ranging study of dexamethasone for preventing nausea and
      vomiting within the first 24 h after the administration of epidural morphine. We
      found that dexamethasone 5 mg was as effective as 10 mg. We recommend the smaller
      dose for this purpose.

PMID- 11226113
TI  - The effect of epidural anesthesia on respiratory distress induced by airway
      occlusion in isoflurane-anesthetized cats.
AB  - The role of afferent information from the chest wall in the genesis of dyspnea is
      not fully elucidated. We have developed an animal model for the study of airway
      occlusion (AO) and proposed new concepts of minimum alveolar anesthetic
      concentration for AO (MACAOR) and the duration from the start of AO to the onset
      of the positive motor response (DOCCL) to evaluate respiratory distress
      quantitatively. We examined the effects of thoracic epidural anesthesia on
      respiratory distress by using our animal model. Adult cats (n = 24) were
      anesthetized with isoflurane, and an epidural catheter was placed after T9
      laminectomy. After determination of MACAOR, DOCCL was measured. Animals were then
      randomly assigned into three groups: the EPD Group (n = 12) received epidural 1%
      lidocaine (0.4 mL/kg), IM saline (0.4 mL/kg), and saline infusion. The IM Group
      (n = 6) received epidural saline (0.4 mL/kg), IM 1% lidocaine (1 mL/kg), and
      saline infusion. The PHE Group (n = 6) received epidural 1% lidocaine (0.4 mL/kg)
      and IV phenylephrine (0.5-1 microg. kg(-1). min(-1)) to maintain a stable
      arterial blood pressure. DOCCL and MACAOR were measured in each animal at 15 min
      after the administration of drugs. Plasma lidocaine concentrations were measured
      before and after epidural or IM injection. DOCCL was significantly longer after
      epidural injection in all groups than before the injection. Although there was no
      significant difference in the values of MACAOR between before and after the
      epidural injection in the EPD Group, the IM administration of lidocaine in the IM
      Group significantly reduced MACAOR. Plasma concentrations of lidocaine were
      similar in all groups at all measurement points. Our data indicate that thoracic
      epidural anesthesia using 1% lidocaine significantly reduced respiratory distress
      induced by AO. This effect is most likely caused by a systemic effect of
      lidocaine rather than by reduced afferent information from the chest wall.
      IMPLICATIONS: Thoracic epidural anesthesia reduced respiratory distress induced
      by airway occlusion. This effect is most likely caused by the systemic effect of
      lidocaine, rather than by the reduced afferent information from the chest wall.

PMID- 11226114
TI  - Diaphragm movement before and after cholecystectomy: a sonographic study.
AB  - Respiratory disorders after abdominal surgery are commonly explained by changes
      in diaphragmatic movement that are difficult to demonstrate and quantify. Our aim
      was thus to quantify these changes using a noninvasive method. We used M-mode
      sonography for the prospective study to measure diaphragmatic amplitude in 14
      patients before and after cholecystectomy. During quiet breathing, the diaphragm
      inspiratory amplitude (DIA) was significantly decreased after surgery from 1.4 +/
      0.2 cm to 1 +/- 0.1 cm and from 1.6 +/- 0.3 cm to 1.2 +/- 0.3 cm in the
      Laparoscopic and Open Cholecystectomy groups, respectively. The total time cycle
      of diaphragmatic motion decreased significantly in the two groups. The DIA also
      decreased significantly during deep breathing after cholecystectomy from 6.0 +/-
      0.8 cm to 3.0 +/- 1.8 cm and from 6.1 +/- 1.3 cm to 3.1 +/- 1.6 cm in the
      Laparoscopic and Open Cholecystectomy groups, respectively. The six patients who
      underwent spirometric examination showed, during quiet breathing, a significant
      decrease in DIA without change in tidal volume, i.e., 0.51 +/- 0.08 L to 0.45 +/-
      0.08 L. We found a significant decrease in DIA after cholecystectomy and a
      significant interindividual correlation between DIA during deep inspiration and
      inspiratory capacity. Using M-mode sonography techniques, we were able to
      demonstrate changes in diaphragmatic mobility after laparoscopic or open
      cholecystectomy. IMPLICATIONS: Cholecystectomy at times results in impaired
      respiratory and diaphragmatic functions. The techniques currently used to study
      these repercussions are both laborious and invasive. Our sonographic technique is
      completely noninvasive and can be used to study diaphragm morphology and movement
      in real time.

PMID- 11226115
TI  - Colforsin daropate improves contractility in fatigued canine diaphragm.
AB  - We studied the effects of colforsin daropate, a water-soluble forskoline
      derivative, on contractility in fatigued canine diaphragm. Dogs were randomly
      divided into 4 groups of 8 each. In each group, diaphragmatic fatigue was induced
      by intermittent supramaximal bilateral electrophrenic stimulation at a frequency
      of 20 Hz applied for 30 min. Immediately after the end of a fatigue-producing
      period, Group 1 received no study drug, Group 2 was infused with small-dose
      colforsin daropate (0.2 microg. kg(-1). min(-1)), Group 3 was infused with large
      dose colforsin daropate (0.5 microg. kg(-1). min(-1)), and Group 4 was infused
      with nicardipne (5 microg. kg(-1). min(-1)) during colforsin daropate (0.5
      microg. kg(-1). min(-1)) administration. After the fatigue-producing period, in
      each group transdiaphragmatic pressure (Pdi) at low-frequency (20-Hz) stimulation
      decreased from baseline values (P < 0.05), whereas there was no change in Pdi at
      high-frequency (100-Hz) stimulation. In Groups 2 and 3, during colforsin daropate
      administration, Pdi to each stimulus increased from fatigued values (P < 0.05).
      The increase in Pdi was larger in Group 3 than in Group 2 (P < 0.05). In Group 4,
      the augmentation of Pdi by colforsin daropate was abolished in fatigued diaphragm
      with an infusion of nicardipine. The integrated diaphragmatic electric activity
      did not change in any of the groups. We conclude that colforsin daropate
      improves, in a dose-dependent manner, contractility in fatigued canine diaphragm
      via its effect on transmembrane calcium movement. IMPLICATIONS: Diaphragmatic
      fatigue is implicated as a cause of respiratory failure in normal subjects and in
      patients with chronic obstructive lung disease. Colforsin daropate improves
      contractile properties during diaphragmatic fatigue.

PMID- 11226116
TI  - The effects of ethanol on CA(2+) sensitivity in airway smooth muscle.
AB  - Halothane and other volatile anesthetics relax air-way smooth muscle (ASM) in
      part by decreasing the amount of force produced for a given intracellular Ca(2+)
      concentration (the Ca(2+) sensitivity) during muscarinic receptor stimulation. To
      determine whether this is a unique property of the volatile anesthetics, we
      tested the hypothesis that ethanol, another compound with anesthetic properties,
      also inhibits calcium sensitization induced by muscarinic stimulation of ASM. A
      beta-escin permeabilized canine tracheal smooth muscle preparation was used.
      Ethanol was applied to permeabilized muscles stimulated with calcium in either
      the absence or presence of acetylcholine. In intact ASM, ethanol produced
      incomplete relaxation (approximately 40%) at concentrations up to 300 mM. Ethanol
      significantly increased Ca(2+) sensitivity both in the presence and the absence
      of muscarinic receptor stimulation. Although ethanol did not affect regulatory
      myosin light chain (rMLC) phosphorylation during stimulation with Ca(2+) alone,
      it decreased rMLC phosphorylation by Ca(2+) during muscarinic receptor
      stimulation. Ethanol, like volatile anesthetics, inhibits increases in rMLC
      phosphorylation produced by muscarinic receptor stimulation at constant
      [Ca(2+)](i). However, despite this inhibition, the net effect of ethanol is to
      increase Ca(2+) sensitivity (defined as the force maintained for a given
      [Ca(2+)](i)) by a mechanism that is independent of changes in rMLC
      phosphorylation. IMPLICATIONS: In permeabilized airway smooth muscle, ethanol,
      like volatile anesthetics, inhibits increases in regulatory protein
      phosphorylation caused by stimulation of the muscle when intracellular calcium
      concentration is constant. However, unlike volatile anesthetics, ethanol causes a
      net increase in force through a process not dependent on protein phosphorylation,
      an action favoring bronchoconstriction.

PMID- 11226117
TI  - Regional hemostatic status and blood requirements after total knee arthroplasty
      with and without tranexamic acid or aprotinin.
AB  - Antifibrinolytics seem to reduce postoperative blood loss after total knee
      arthroplasty. Few studies have shown the impact of these drugs on the mechanisms
      of coagulation. The purpose of this study was to examine coagulation/fibrinolysis
      variables as well as blood loss after total knee arthroplasty with and without
      antifibrinolytics in the operated limb on a regional level. Thirty-six patients
      were randomized into one of three groups to receive aprotinin, tranexamic acid,
      or no medication. We took blood samples of the femoral vein before deflating the
      tourniquet and after 5, 10, 30, 60, 120 min and on the first postoperative day.
      The implantation of a knee prosthesis in artificial ischemia caused a significant
      activation of coagulation and fibrinolysis in the regional circulation.
      Tranexamic acid and aprotinin did not cause a significant modulation of
      fibrinolysis variables or a significant reduction of postoperative bleeding and
      transfusion requirements. One of the differences in comparison to other studies
      was the decreased total blood loss. The use of bone cement as well as surgical
      hemostasis before wound closure may be regarded as reasons for this. Therefore,
      primarily these methods should be used because there is no increased risk of
      adverse drug effects. IMPLICATIONS: After total knee arthroplasty total blood
      loss may be kept in a low range if methods such as cemented knee prosthesis and
      surgical hemostasis are used. In this case aprotinin and tranexamic acid did not
      cause a significant modulation of fibrinolysis variables or a significant
      reduction of postoperative bleeding.

PMID- 11226118
TI  - Propofol is not effective for hyperventilation syndrome.

PMID- 11226119
TI  - Difficult tracheal intubation as a result of unsuspected abnormality of the
      temporomandibular joint.

PMID- 11226120
TI  - Considerations for the hemophiliac patient with inhibitors to factor VIII.

PMID- 11226121
TI  - Evidence-based medicine in anesthesiology.
AB  - By making the clinical decision making process explicit, conscious, and science
      based, we may avoid confusing opinion with evidence. EBM may help sharpen our
      critical appraisal skills and thus improve the way we practice, teach, and
      conduct research. Nevertheless, EBM will need to supplement rather than
      substitute for other approaches to patient care and teaching. EBM may better
      incorporate patients' values into clinical decision making, and this may be
      especially important in anesthesiology, where we are in need of valid evidence
      about important clinical issues such as preoperative testing and postoperative
      analgesia. By incorporating valid scientific evidence and patients' values into
      clinical decision making, we may improve patient outcomes. Outside of internal
      medicine, the literature suggesting that the practice of EBM improves outcomes is
      sparse, though increasing. Future studies to critically evaluate the practice of
      EBM in anesthesiology and critical care would be helpful.

PMID- 11226122
TI  - Eliciting paresthesias for peripheral nerve block: a harmful clinical standard?

PMID- 11226123
TI  - The analgesic potency of NMDA-antagonists--a question of mechanism-based use and
      timing?

PMID- 11226124
TI  - Keep it simple.

PMID- 11226125
TI  - Power analysis with more than two groups.

PMID- 11226126
TI  - Cannabinoid inhibition of the capsaicin-induced calcium response in rat dorsal
      root ganglion neurones.
AB  - Cannabinoids have marked inhibitory effects on somatosensory processing, which
      may arise from actions at both peripheral and central cannabinoid receptors.
      Here, the effect of a synthetic cannabinoid agonist HU210 on capsaicin-evoked
      responses in adult rat dorsal root ganglion (DRG) neurones was studied. The
      vanilloid capsaicin produced a concentration-related increase in intracellular
      calcium in DRG neurones, which was significantly inhibited by HU210 (1 microM).
      The cannabinoid CB(1) receptor antagonist SR141716A (1 microM) had no effect
      alone and did not influence the response to capsaicin but significantly reversed
      the inhibitory effect of HU210. These data indicate that DRG CB(1) receptors are
      functional and can inhibit nociceptive responses.

PMID- 11226127
TI  - Interaction of stilbene disulphonates with cloned K(ATP) channels.
AB  - In this study, we tested the effects of the stilbene disulphonates DIDS and SITS
      on three different types of cloned K(ATP) channel (Kir6.2/SUR1, Kir6.2/SUR2A and
      Kir6.2DeltaC) heterologously expressed in Xenopus oocytes, with the aim of
      identifying the part of the channel which is involved in mediating disulphonate
      inhibition. We found that the inhibitory site(s) for these drugs lies within the
      Kir6.2 subunit of the channel, although its properties are further modulated by
      the sulphonylurea (SUR) subunit. In particular, SUR2A reduces both the rate and
      extent of block, by impairing the ability of DIDS binding to produce channel
      closure. The disulphonate-binding site interacts with the ATP inhibitory site on
      Kir6.2 because ATP is able to protect against irreversible channel inhibition by
      disulphonates. This effect is not mimicked by tolbutamide (at a concentration
      that interacts with Kir6.2) and is abolished by mutations that render the channel
      ATP insensitive. A number of point mutations in both the N and C termini of
      Kir6.2 reduced the extent and reversibility of channel inhibition by SITS. The
      results are consistent with the idea that residue C42 of Kir6.2 is likely to be
      involved in covalently linking of SITS to the channel. Other types of Kir channel
      (Kir1.1, Kir2.1 and Kir4.1) were also irreversibly blocked by DIDS, suggesting
      that these channels may share common binding sites for these stilbene
      disulphonates.

PMID- 11226128
TI  - Evidence for 5-HT(1B/1D) and 5-HT(2A) receptors mediating constriction of the
      canine internal carotid circulation.
AB  - The present study has investigated the preliminary pharmacological profile of the
      receptors mediating vasoconstriction to 5-hydroxytryptamine (5-HT) in the
      internal carotid bed of vagosympathectomised dogs. One minute intracarotid
      infusions of the agonists 5-HT (0.1 - 10 microg min(-1)), sumatriptan (0.3 - 10
      microg min(-1); 5-HT(1B/1D)), 5-methoxytryptamine (1 - 100 microg min(-1); 5
      HT(1), 5-HT(2), 5-HT(4), 5-ht(6) and 5-HT(7)) or DOI (0.31 - 10 microg min(-1); 5
      HT(2)), but not 5-carboxamidotryptamine (0.01 - 0.3 microg min(-1); 5-HT(1), 5
      ht(5A) and 5-HT(7)), 1-(m-chlorophenyl)-biguanide (mCPBG; 1 - 1000 microg min(
      1); 5-HT(3)) or cisapride (1 - 1000 microg min(-1); 5-HT(4)), resulted in dose
      dependent decreases in internal carotid blood flow, without changing blood
      pressure or heart rate. The vasoconstrictor responses to 5-HT, which remained
      unaffected after saline, were resistant to blockade by i.v. administration of the
      antagonists ritanserin (100 microg kg(-1); 5-HT(2A/2B/2C)) in combination with
      tropisetron (3000 microg kg(-1); 5-HT(3/4)) or the cyclo-oxygenase inhibitor,
      indomethacin (5000 microg kg(-1)), but were abolished by the 5-HT(1B/1D) receptor
      antagonist, GR127935 (30 microg kg(-1)). Interestingly, after administration of
      GR127935, the subsequent administration of ritanserin unmasked a dose-dependent
      vasodilator component. GR127935 or saline did not practically modify the
      vasoconstrictor effects of 5-MeO-T. In animals receiving GR127935, the subsequent
      administration of ritanserin abolished the vasoconstrictor responses to 5-MeO-T
      unmasking a dose-dependent vasodilator component. The vasoconstriction induced by
      sumatriptan was antagonized by GR127935, but not by ritanserin. Furthermore,
      ritanserin (100 microg kg(-1)) or ketanserin (100 microg kg(-1); 5-HT(2A)), but
      not GR127935, abolished DOI-induced vasoconstrictor responses. The above results
      suggest that 5-HT-induced internal carotid vasoconstriction is predominantly
      mediated by 5-HT(1B/1D) and 5-HT(2A) receptors.

PMID- 11226129
TI  - The GR127935-sensitive 5-HT(1) receptors mediating canine internal carotid
      vasoconstriction: resemblance to the 5-HT(1B), but not to the 5-HT(1D) or 5
      ht(1F), receptor subtype.
AB  - This study has further investigated the pharmacological profile of the GR127935
      sensitive 5-HT(1) receptors mediating vasoconstriction in the internal carotid
      bed of anaesthetized vagosympathectomized dogs. One-minute intracarotid infusions
      of the agonists 5-hydroxytryptamine (5-HT; 0.1 - 10 microg min(-1); endogenous
      ligand) and sumatriptan (0.3 - 10 microg min(-1); 5-HT(1B/1D)), but not PNU
      142633 (1 - 1000 microg min(-1); 5-HT(1D)) or LY344864 (1 - 1000 microg min(-1);
      5-ht(1F)), produced dose-dependent decreases in internal carotid blood flow
      without changing blood pressure or heart rate. The responses to 5-HT were
      apparently resistant to blockade by i.v. administration of the antagonists
      SB224289 (300 microg kg(-1); 5-HT(1B)), BRL15572 (300 microg kg(-1); 5-HT(1D)) or
      ritanserin (100 microg kg(-1); 5-HT(2)). In contrast, the responses to
      sumatriptan were antagonized by SB224289, but not by BRL15572. In the animals
      receiving SB224289, but not those receiving BRL15572, the subsequent
      administration of ritanserin abolished the 5-HT-induced vasoconstriction and
      unmasked a vasodilator component. Similarly, in ritanserin-treated animals, the
      subsequent administration of SB224289, but not BRL15572, completely blocked the 5
      HT-induced vasoconstriction, revealing vasodilatation. In animals receiving
      initially BRL15572, the subsequent administration of SB224289 did not affect
      (except at 10 microg min(-1)) the vasoconstrictor responses to 5-HT. Notably, in
      animals pretreated with 1000 microg kg(-1) of mesulergine, a 5-HT(2/7) receptor
      antagonist, 5-HT produced a dose-dependent vasoconstriction, which was
      practically abolished by SB224289. After BRL15572, no further blockade was
      produced and the subsequent administration of ritanserin was similarly inactive.
      These results suggest that the GR127935-sensitive 5-HT(1) receptors mediating
      canine internal carotid vasoconstriction resemble the 5-HT(1B) but not the 5
      HT(1D) or 5-ht(1F), receptor subtype.

PMID- 11226130
TI  - Prostaglandin E(2) increases cyclic AMP and inhibits endothelin-1
      production/secretion by guinea-pig tracheal epithelial cells through EP(4)
      receptors.
AB  - Prostaglandin E(2) (PGE(2)) increased adenosine 3' : 5'-cyclic monophosphate
      (cyclic AMP) formation in tracheal epithelial cells and concomitantly decreased
      the production/secretion of immunoreactive endothelin (irET). Naturally occurring
      prostanoids and selective and non-selective EP receptor agonists showed the
      following rank order of potency in stimulating cyclic AMP generation by
      epithelial cells: PGE(2) (EP-selective)>16,16-dimethyl PGE(2) (EP-selective)>11
      deoxy PGE(2) (EP-selective)>>>iloprost (IP/EP(1)/EP(3)-selective), butaprost
      (EP(2)-selective), PGD(2) (DP-selective), PGF(2alpha) (FP-selective). The lack of
      responsiveness of the latter prostanoids indicated that the prostanoid receptor
      present in these cells is not of the DP, FP, IP, EP(1), EP(2) or EP(3) subtype.
      Pre-incubating the cells with the selective TP/EP(4)-receptor antagonists
      AH23848B and AH22921X antagonized the PGE(2)-evoked cyclic AMP generation. This
      suggested that EP(4) receptors mediate PGE(2) effects. However, in addition to
      any antagonistic effects at EP(4)-receptors, both compounds, to a different
      extent, modified cyclic AMP metabolism. The selective EP(1), DP and EP(2)
      receptor antagonist (AH6809) failed to inhibit PGE(2)-evoked cyclic AMP
      generation which confirmed that the EP(2) receptor subtype did not contribute to
      the change in cyclic AMP formation in these cells. The PGE(2)-induced inhibition
      of irET production by guinea-pig tracheal epithelial cells was due to cyclic AMP
      generation and activation of the cyclic AMP-dependent protein kinase since this
      effect was reverted by the cyclic AMP antagonist Rp-cAMPS. These results provide
      the first evidence supporting the existence of a functional prostaglandin E(2)
      receptor that shares the pharmacological features of the EP(4)-receptor subtype
      in guinea-pig tracheal epithelial cells. These receptors modulate cyclic AMP
      formation as well as ET-1 production/secretion in these cells.

PMID- 11226131
TI  - Analysis of the muscarinic receptor subtype mediating inhibition of the
      neurogenic contractions in rabbit isolated vas deferens by a series of
      polymethylene tetra-amines.
AB  - The pharmacological characteristics of the presynaptic muscarinic receptor
      subtype, which mediates inhibition of the neurogenic contractions in the
      prostatic portion of rabbit vas deferens, have been investigated by using a
      series of polymethylene tetra-amines, which were selected for their ability to
      differentiate among muscarinic receptor subtypes. It was found that all tetra
      amines antagonized McN-A-343-induced inhibition in electrically stimulated rabbit
      vas deferens in a competitive manner and with affinity values (pA:(2)) ranging
      between 6.27+/-0.09 (spirotramine) and 8.51+/-0.02 (AM170). Competition
      radioligand binding studies, using native muscarinic receptors from rat tissues
      (M(1), cortex; M(2), heart; M(3), submaxillary gland) or from NG 108-15 cells
      (M(4)) and human cloned muscarinic M(1)-M(4) receptors expressed in CHO-K1 cells,
      were undertaken with the same tetra-amines employed in functional assays. All
      antagonists indicated a one-site fit. The affinity estimates (pK:(i)) of tetra
      amines calculated in binding assays using native receptors were similar to those
      obtained using cloned receptors. Among these compounds some displayed selectivity
      between muscarinic receptor subtypes, indicating that they may be valuable tools
      in receptor characterization. Spirotramine was selective for M(1) receptors
      versus all other subtypes (pK:(i) native: M(1), 7.32+/-0.10; M(2), 6.50+/-0.11;
      M(3), 6.02+/-0.13; M(4), 6.28+/-0.16; pK:(i) cloned: M(1), 7.69+/-0.08; M(2),
      6.22+/-0.14; M(3), 6.11+/-0.16; 6.35+/-0.11) whereas CC8 is highly selective for
      M(2) receptors versus the other subtypes (pK:(i) native: M(1), 7.50+/-0.04; M(2),
      9.01+/-0.12; M(3), 6.70+/-0.08; M(4), 7.56+/-0.04; pK:(i) cloned: M(1), 7.90+/
      0.20; M(2), 9.04+/-0.08; M(3), 6.40+/-0.07; M(4), 7.40+/-0.04). Furthermore,
      particularly relevant for this investigation were tetra-amines dipitramine and
      AM172 for their ability to significantly differentiate M(1) and M(4) receptors.
      The apparent affinity values (pA:(2)) obtained for tetra-amines in functional
      studies using the prostatic portion of rabbit vas deferens correlated most
      closely with the values (pK:(i)) obtained at either native or human recombinant
      muscarinic M(4) receptors. This supports the view that the muscarinic receptor
      mediating inhibition of neurogenic contractions of rabbit vas deferens may not
      belong to the M(1) type but rather appears to be of the M(4) subtype.

PMID- 11226132
TI  - Cyclic AMP-dependent inhibition of human neutrophil oxidative activity by
      substituted 2-propynylcyclohexyl adenosine A(2A) receptor agonists.
AB  - Novel 2-propynylcyclohexyl-5'-N:-ehtylcarboxamidoadenosines, trans-substituted in
      the 4-position of the cyclohexyl ring, were evaluated in binding assays to the
      four subtypes of adenosine receptors (ARs). Two esters, 4-(3-[6-amino-9-(5
      ethylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl)
      cyclohexanecarboxylic acid methyl ester (ATL146e) and acetic acid 4-(3-[6-amino-9
      (5-ethylcarbamoyl-3, 4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl] -prop-2
      ynyl)-cyclohexylmethyl ester (ATL193) were >50 x more potent than 2-[4-(2
      carboxyethyl)phenethylamino]-5'-N:-ethylcarboxamidoadenosine (CGS21680) for human
      A(2A) AR binding. Human A(2A) AR affinity for substituted cyclohexyl
      propynyladenosine analogues was inversely correlated with the polarity of the
      cyclohexyl side chain. There was a comparable order of potency for A(2A) AR
      agonist stimulation of human neutrophil [cyclic AMP](i), and inhibition of the
      neutrophil oxidative burst. ATL146e and CGS21680 were approximately equipotent
      agonists of human A(3) ARs. We measured the effects of selective AR antagonists
      on agonist stimulated neutrophil [cyclic AMP](i) and the effect of PKA inhibition
      on A(2A) AR agonist activity. ATL193-stimulated neutrophil [cyclic AMP](i) was
      blocked by antagonists with the potency order: ZM241385 (A(2A)-selective)>MRS1220
      (A(3)-selective)>>N-(4-Cyano-phenyl)-2-[4-(2,6-dioxo-1,3-dipropyl-2,3,4,5,6,7
      hexahydro-1H-purin-8-yl)-phenoxy]-acetamide (MRS1754; A(2B)-selective)
      approximately 8-(N-methylisopropyl)amino-N(6)-(5'-endohydroxy-endonorbornyl)-9
      methyladenine (WRC0571; A(1)-selective). The type IV phosphodiesterase inhibitor,
      rolipram (100 nM) potentiated ATL193 inhibition of the oxidative burst, and
      inhibition by ATL193 was counteracted by the PKA inhibitor H-89. The data
      indicate that activation of A(2A)ARs inhibits neutrophil oxidative activity by
      activating [cyclic AMP](i)/PKA.

PMID- 11226133
TI  - Glucuronide and glucoside conjugation of mycophenolic acid by human liver, kidney
      and intestinal microsomes.
AB  - Mycophenolic acid (MPA) is primarily metabolized to a phenolic glucuronide (MPAG)
      as well as to two further minor metabolites: an acyl glucuronide (AcMPAG) and a
      phenolic glucoside (MPAG1s). This study presents investigations of the formation
      of these metabolites by human liver (HLM), kidney (HKM), and intestinal (HIM)
      microsomes, as well as by recombinant UDP-glucuronosyltransferases. HLM (n=5),
      HKM (n=6), HIM (n=5) and recombinant UGTs were incubated in the presence of
      either UDP-glucuronic acid or UDP-glucose and various concentrations of MPA.
      Metabolite formation was followed by h.p.l.c. All microsomes investigated formed
      both MPAG and AcMPAG. Whereas the efficiency of MPAG formation was greater with
      HKM compared to HLM, AcMPAG formation was greater with HLM than HKM. HIM showed
      the lowest glucuronidation efficiency and the greatest interindividual variation.
      The capacity for MPAGls formation was highest in HKM, while no glucoside was
      detected with HIM. HKM produced a second metabolite when incubated with MPA and
      UDP-glucose, which was labile to alkaline treatment. Mass spectrometry of this
      metabolite in the negative ion mode revealed a molecular ion of m/z 481
      compatible with an acyl glucoside conjugate of MPA. All recombinant UGTs
      investigated were able to glucuronidate MPA with K:(M:) values ranging from 115.3
      to 275.7 microM l(-1) and V(max) values between 29 and 106 pM min(-1) mg protein(
      1). Even though the liver is the most important site of MPA glucuronidation,
      extrahepatic tissues particularly the kidney may play a significant role in the
      overall biotransformation of MPA in man. Only kidney microsomes formed a putative
      acyl glucoside of MPA.

PMID- 11226135
TI  - Alteration of excitation-contraction coupling mechanism in extensor digitorum
      longus muscle fibres of dystrophic mdx mouse and potential efficacy of taurine.
AB  - No clear data is available about functional alterations in the calcium-dependent
      excitation-contraction (e-c) coupling mechanism of dystrophin-deficient muscle of
      mdx mice. By means of the intracellular microelectrode "point" voltage clamp
      method, we measured the voltage threshold for contraction (mechanical threshold;
      MT) in intact extensor digitorum longus (EDL) muscle fibres of dystrophic mdx
      mouse of two different ages: 8 - 12 weeks, during the active regeneration of hind
      limb muscles, and 6 - 8 months, when regeneration is complete. The EDL muscle
      fibres of 8 - 12-week-old wildtype animals had a more negative rheobase voltage
      (potential of equilibrium for contraction- and relaxation-related calcium
      movements) with respect to control mice of 6 - 8 months. However, at both ages,
      the EDL muscle fibres of mdx mice contracted at more negative potentials with
      respect to age-matched controls and had markedly slower time constants to reach
      the rheobase. The in vitro application of 60 mM taurine, whose normally high
      intracellular muscle levels play a role in e-c coupling, was without effect on 6 
      8-month-old wildtype EDL muscle, while it significantly ameliorated the MT of
      mdx mouse. HPLC determination of taurine content at 6 - 8 months showed a
      significant 140% rise of plasma taurine levels and a clear trend toward a
      decrease in amino acid levels in hind limb muscles, brain and heart, suggesting a
      tissue difficulty in retaining appropriate levels of the amino acid. The data is
      consistent with a permanent alteration of e-c coupling in mdx EDL muscle fibres.
      The alteration could be related to the proposed increase in intracellular
      calcium, and can be ameliorated by taurine, suggesting a potential therapeutic
      role of the amino acid.

PMID- 11226134
TI  - Alterations in EDHF-mediated hyperpolarization and relaxation in mesenteric
      arteries of female rats in long-term deficiency of oestrogen and during oestrus
      cycle.
AB  - This study was undertaken to determine whether endothelium-dependent relaxations
      are altered in mesenteric arteries from young female rats during oestrus cycle
      and after castration. The contractile response to phenylephrine (Phe) was
      significantly enhanced in arteries from rats subjected to ovariectomy than in
      those from sham-operated (control) rats. Treatment of ovariectomized rats with
      17beta-oestradiol returned the Phe response to the control level. Arteries from
      rats at the diestrus stage also exhibited greater contraction in response to Phe.
      In the presence of 100 microM N(G)-nitro-L-arginine (L-NOARG), the enhancement of
      the Phe contractile response associated with oestrogen deficiency was not
      observed. Endothelium-dependent relaxations elicited by acetylcholine (ACh) in
      arteries precontracted with Phe were significantly reduced in ovariectomized and
      diestrus rats regardless of whether endothelium-derived nitric oxide (NO) was
      blocked with L-NOARG. Treatment with 17beta-oestradiol prevented the reduced
      vascular relaxant response to ACh in ovariectomized rats. The reduction in the
      ACh responses observed in ovariectomized and diestrus rats was eliminated when
      500 nM apamin and 100 nM charybdotoxin were present. ACh-induced endothelium
      dependent hyperpolarizations were depressed in arteries from ovariectomized and
      diestrus rats. The hyperpolarizing response to ACh was significantly improved
      when ovariectomized rats were treated with 17beta-oestradiol. The resting
      membrane potentials and pinacidil-induced hyperpolarizations were unaffected by
      ovariectomy or the diestrus stage. These results suggest that oestrogen-deficient
      states of both short and long duration reduce the basal release of NO from the
      endothelium and specifically attenuate endothelium-dependent hyperpolarization
      and relaxation transduced by endothelium-derived hyperpolarizing factor.

PMID- 11226136
TI  - Effects of the oestrous cycle and gender on acute vasodilatory responses of
      isolated pressurized rat mesenteric arteries to 17 beta-oestradiol.
AB  - The influence of the oestrous cycle and gender on responses of isolated
      pressurized mesenteric arteries to acute 17 beta-oestradiol was investigated. All
      vessels, pre-contracted with 60 mM KCl or 10 microM U46619 (9,11 dideoxy-11alpha,
      9alpha-epoxy methano-prostaglandin), exhibited concentration-dependent
      vasodilatory responses to 17 beta-oestradiol (3 - 30 microM). The largest
      responses were seen in vessels from female rats in pro-oestrous (38.9+/-5.4%
      U46619 max and 63.1+/-4.0% KCl max for 30 microM oestradiol), the smallest from
      animals in di-oestrous (20.1+/-3.7% U46619 and 50.1+/-4.5% KCL - both P:<0.05 cf
      pro-oestrous (all n=8)). Responses of vessels from male rats were similar to
      those from pro-oestrous rats (41.5+/-9.1% U46619 (n=10) and 54.9+/-2.9% KCl (n
      =8)). All responsees were unaffected by inhibition of nitric oxide synthase
      (NOS). Female rats in pro-oestrous had the highest plasma concentrations of 17
      beta-oestradiol and testosterone (40.76+/-4.73 pg ml(-1) and 0.29+/-0.05 ng ml(
      1) respectively (n=8)) while those in di-oestrous had the lowest (15.24+/-3.94 pg
      ml(-1) for oestradiol and 0.08+/-0.03 ng ml(-1) for testosterone (n=8)). In male
      rats the concentration of oestrogen was 10.29+/-1.21 pg ml(-1) (n=7) while that
      of testosterone was 3.15+/-0.36 ng ml(-1) (n=7). Incubation of arteries isolated
      from male rats and from female rats in pro-oestrous and di-oestrous with
      testosterone (1 microM, 3 h) significantly enhanced the subsequent vasodilatory
      responses to acute 17 beta-oestradiol. Following incubation, the responses to 17
      beta-oestradiol were similar in all groups. These observations suggest that
      gender and the oestrous cycle may influence the vascular responses to acute 17
      beta-oestradiol administration.

PMID- 11226137
TI  - Mitochondrial involvement in cocaine-treated rat hepatocytes: effect of N
      acetylcysteine and deferoxamine.
AB  - The cytotoxicity of cocaine (0 - 1000 microM), was studied on parameters related
      to the mitochondrial role and the cascade of events that lead to apoptosis in
      hepatocyte cultures from phenobarbitone (PB) pretreated rats. Cytotoxicity was
      dose-dependent and LDH leakage was significantly enhanced above 100 microM
      cocaine. Apoptosis was visualized by DNA fragmentation on agarose gel, and
      appeared at 50 and 100 microM cocaine. Cocaine induced biphasic changes in
      mitochondrial transmembrane potential and significantly increased the
      mitochondrial release of cytochrome c, the caspase-3 like DEVDase activity and
      the level of 20 kDa subunit, a product of pro-caspase-3 cleavage. The protective
      effect of N-acetylcysteine (NAC) and deferoxamine (DFO) on all these parameters
      confirmed the involvement of oxygen radicals in cocaine-induced
      necrosis/apoptosis. We conclude: first, that the biphasic changes recorded in
      mitochondrial inner membrane potential by the effect of cocaine, were parallel to
      apoptosis; second, that caspase-3 activity and cleavage to it p20 subunit
      increased sharply in parallel to the translocation of cytochrome c from
      mitochondria to cytosol; and third, that the antioxidants, NAC or DFO exerted a
      noticeable protective role in counteracting the cytotoxicity of cocaine, these
      effects being more pronounced in the case of DFO than NAC. These findings
      demonstrate that cocaine cytotoxicity involves mitochondrial damage.

PMID- 11226138
TI  - Comparative effects of frovatriptan and sumatriptan on coronary and internal
      carotid vascular haemodynamics in conscious dogs.
AB  - The effects of frovatriptan and sumatriptan on internal carotid and coronary
      vascular haemodynamics were investigated and compared in conscious dogs.
      Frovatriptan and sumatriptan (0.1 - 100 microg kg(-1)) induced a transient
      increase in external coronary artery diameter (eCOD) of up to 2.9+/-1.2 and 1.8+/
      0.6%, respectively (both P:<0.05). This was followed by a prolonged and dose
      dependent decrease in eCOD of up to -5.2+/-1.2 and -5.3+/-0.9% (both P:<0.05),
      with ED(50) values of 86+/-21 and 489+/-113 micromol kg(-1), respectively. In
      contrast, only a decrease in the external diameter of the internal carotid artery
      was observed (-6.0+/-0.6 and -6.2+/-1.4%, both P:<0.05, and ED(50) values of 86+/
      41 and 493+/-162 micromol kg(-1), respectively). Frovatriptan was thus 5.7 fold
      more potent than sumatriptan at the level of both large coronary and internal
      carotid arteries. After endothelium removal by balloon angioplasty in coronary
      arteries, the initial dilatation induced by the triptans was abolished and
      delayed constriction enhanced. The selective antagonist for the 5-HT(1B)
      receptors SB224289 dose-dependently blocked the effects of sumatriptan on large
      coronary and internal carotid arteries whereas the selective antagonist for the 5
      HT(1D) receptors BRL15572 did not affect any of these effects. In conclusion,
      frovatriptan and sumatriptan initially dilate and subsequently constrict large
      coronary arteries in the conscious dog, whereas they directly constrict the
      internal carotid artery. The vascular endothelium modulates the effects of these
      triptans on large coronary arteries. Finally, 5-HT(1B) but not 5-HT(1D) receptors
      are primarily involved in canine coronary and internal carotid vasomotor
      responses to sumatriptan.

PMID- 11226139
TI  - Pharmacological differences between the human and rat vanilloid receptor 1 (VR1).
AB  - Vanilloid receptors (VR1) were cloned from human and rat dorsal root ganglion
      libraries and expressed in Xenopus oocytes or Chinese Hamster Ovary (CHO) cells.
      Both rat and human VR1 formed ligand gated channels that were activated by
      capsaicin with similar EC(50) values. Capsaicin had a lower potency on both
      channels, when measured electrophysiologically in oocytes compared to CHO cells
      (oocytes: rat=1.90+/-0.20 microM; human=1.90+/-0.30 microM: CHO cells: rat=0.20+/
      0.06 microM; human=0.19+/-0.08 microM). In CHO cell lines co-expressing either
      rat or human VR1 and the calcium sensitive, luminescent protein, aequorin, the
      EC(50) values for capsaicin-induced responses were similar in both cell lines
      (rat=0.35+/-0.06 microM, human=0.53+/-0.03 microM). The threshold for activation
      by acidic solutions was lower for human VR1 channels than that for rat VR1
      (EC(50) pH 5.49+/-0.04 and pH 5.78+/-0.09, respectively). The threshold for heat
      activation was identical (42 degrees C) for rat and human VR1. PPAHV was an
      agonist at rat VR1 (EC(50) between 3 and 10 microM) but was virtually inactive at
      the human VR1 (EC(50)>10 microM). Capsazepine and ruthenium red were both more
      potent at blocking the capsaicin response of human VR1 than rat VR1. Capsazepine
      blocked the human but not the rat VR1 response to low pH. Capsazepine was also
      more effective at inhibiting the noxious heat response of human than of rat VR1.

PMID- 11226140
TI  - Protein phosphatase inhibitors facilitate DHPG-induced LTD in the CA1 region of
      the hippocampus.
AB  - We have shown earlier that activation of metabotropic glutamate (mGlu) receptors
      using a group I-specific mGlu receptor agonist, (RS)-3,5-dihydroxyphenylglycine
      (DHPG), can induce long-term depression (LTD) in the CA1 region of the
      hippocampus. In an attempt to determine the signal transduction mechanisms
      involved in this form of synaptic plasticity, we have tested the effects of a
      range of inhibitors on DHPG-induced LTD. In vitro grease-gap electrophysiological
      recordings were performed in the rat hippocampal CA1 region. We have found that
      DHPG-induced LTD is resistant to the two potent protein kinase C (PKC)
      inhibitors, Go 6976 (10 microM) and Go 6983 (10 microM), the potent and selective
      protein kinase A (PKA) inhibitor, KT 5720 (10 microM), and the potent broad
      spectrum kinase inhibitor, staurosporine (10 microM). In contrast, non-selective
      inhibitors of protein phosphatases (PP1 and PP2A), okadaic acid (1 microM) or
      calyculin A (1 microM), facilitated DHPG-induced LTD. However, an inhibitor of
      protein phosphatase 2B, FK 506 (1 microM), did not influence this process. The
      PP1/PP2A protein phosphatase inhibitors, but none of the other agents tested,
      also inhibited (S)-alpha-methyl-4-carboxyphenylglycine (MCPG)-induced reversal of
      DHPG-induced LTD. These data suggest that activation of neither PKC nor PKA is
      involved in DHPG-induced LTD. They do, however, suggest that the process is under
      regulation by protein phosphorylation and dephosphorylation.

PMID- 11226141
TI  - Ligand internalization and recycling by human recombinant somatostatin type 4 (h
      sst(4)) receptors expressed in CHO-K1 cells.
AB  - There is controversy as to whether somatostatin sst(4) receptors internalize. In
      this study, CHO-K1 cells expressing human sst(4) receptor (CHOsst(4) cells) cells
      internalized [(125)I]-[(11)Tyr]-SRIF in a time-dependent manner, reaching a
      steady state at 60 min (1.4+/-0.1x10(4) molecules internalized per cell).
      Internalization was blocked by hypertonic sucrose (0.5 M), ATP depletion or by
      decreasing the temperature to 4 degrees C. Internalization of [(125)I]-[(11)Tyr]
      SRIF was also inhibited (pIC(50) values) by increasing concentrations of SRIF
      (7.74), L-362855 (6.27) and NNC-296100 (6.50) with pIC(50) values approximately
      10 fold lower than those obtained for inhibition of [(125)I]-[(11)Tyr]-SRIF
      binding to membrane homogenates. Internalized ligand recycled rapidly to the
      extracellular media (t(1/2) 3.9+/-0.7 min) with only 6.8+/-0.6% of internalized
      radioactivity remaining in the cell after 45 min. Confocal microscopy of
      permeabilized, HA-epitope tagged CHOsst(4) cells labelled with a Cy-3 conjugated
      antibody revealed little internal immunostaining after SRIF (1 microM) treatment,
      consistent with the small proportion of receptors (3.5%) estimated to be
      internalized by radioimmunoassay. In summary, CHOsst(4) cells internalized
      [(125)I]-[(11)Tyr]-SRIF in a clathrin- and ATP-dependent manner with subsequent
      rapid recycling to the extracellular medium. Rapid receptor recycling and the
      consequent low proportion of receptors internalized at any one time may explain
      the inability to visualize internalized receptors by confocal microscopy. It
      seems unlikely therefore that the marked receptor desensitization observed in
      CHOsst(4) cells following SRIF treatment can be accounted for by a decrease in
      cell surface receptor expression.

PMID- 11226143
TI  - Potentiation of the antinociceptive effect of clomipramine by a 5-ht(1A)
      antagonist in neuropathic pain in rats.
AB  - The benefit of antidepressant treatment in human neuropathic pain is now well
      documented, but the effect is limited and slow to appear. It has been
      demonstrated that the association of a 5-HT(1A) antagonist and a serotoninergic
      antidepressant reduced the delay of action and increases the thymoanaleptic
      effect of the drug. The purpose of this work was to evaluate the combination of
      an antidepressant and a 5-HT(1A) antagonist in animal models of chronic
      neuropathic pain. We studied the antinociceptive effect of the co-administration
      of clomipramine and a 5-HT(1A) antagonist (WAY 100,635) in a pain test applied in
      normal rats and in two models of neurogenic sustained pain (mononeuropathic and
      diabetic rats). The results show an increase in the antinociceptive effect of
      acutely injected clomipramine due to WAY 100,635 in these models, which is
      majored when the two drugs are repeatedly injected. The 5-HT(1A) antagonist
      reduced the delay of onset and increased the maximal antinociceptive effect of
      clomipramine. These new findings argue for using the combination of an
      antidepressant and a 5-HT(1A) antagonist in human neuropathic pain therapy.

PMID- 11226142
TI  - Involvement of cyclic AMP systems in morphine physical dependence in mice:
      prevention of development of morphine dependence by rolipram, a phosphodiesterase
      4 inhibitor.
AB  - In this study, we examined whether morphine dependence was inhibited by rolipram,
      a cyclic AMP selective phosphodiesterase inhibitor in mice, since a role for the
      cyclic AMP systems in the development of morphine dependence has been reported.
      Mice, which received morphine (10 mg kg(-1) s.c.) twice a day for 5 days showed
      withdrawal syndromes such as jumping, rearing and forepaw tremor following
      naloxone challenge (5 mg kg(-1) i.p.) on the 6th day. Such mice exhibited a
      significant elevation of cyclic AMP levels in the thalamus compared to control
      mice. However, co-administration of rolipram (1 mg kg(-1) i.p.) with morphine for
      5 days significantly attenuated the severity of the withdrawal syndrome and the
      increase in the cyclic AMP levels after the administration of naloxone. In naive
      mice, acute morphine treatment (10 mg kg(-1) s.c.) decreased cyclic AMP levels in
      the thalamus and cerebral cortex 10 min later. The decrease of cyclic AMP levels
      induced by acute morphine treatment was blocked by co-administration of rolipram
      (1 mg kg(-1) i.p.). However, acute rolipram did not affect the naloxone
      precipitated morphine withdrawal syndrome. These results suggest that the
      elevation of the cyclic AMP levels is involved in the development of morphine
      withdrawal syndrome and that blockade of the morphine-induced reduction of cyclic
      AMP levels by chronic rolipram inhibits the development of dependence and the
      behavioural and biochemical changes induced by naloxone. Furthermore, rolipram
      may be a useful drug for attenuating the development of morphine dependence.

PMID- 11226144
TI  - The endogenous cannabinoid agonist, anandamide stimulates sensory nerves in
      guinea-pig airways.
AB  - The endogenous cannabinoid agonist, anandamide produced a modest contractile
      response in guinea-pig isolated bronchus compared with the vanilloid receptor
      agonist capsaicin. The contractile response to both anandamide and capsaicin was
      inhibited by the vanilloid receptor antagonist, capsazepine. Furthermore, the
      NK(2)-selective antagonist, SR48968 but not the NK(1)-selective antagonist,
      SR140333 inhibited contractile responses to anandamide. The contractile response
      to anandamide was abolished in tissues desensitized by capsaicin. However,
      anandamide failed to cross-desensitize the contractile response to capsaicin. The
      contractile response to anandamide was not significantly altered in the presence
      of the CB(1) receptor antagonist, SR141716A, nor the amidase inhibitor,
      phenylmethylsulphonyl fluoride (PMSF) but was significantly increased in the
      presence of the neutral endopeptidase inhibitor, thiorphan. The cannabinoid
      agonist, CP55,940 failed to significantly attenuate the excitatory non-adrenergic
      non-cholinergic (eNANC) response in guinea-pig airways. In contrast, the ORL(1)
      receptor agonist, nociceptin, significantly inhibited this response. The results
      demonstrate that anandamide induces a modest contractile response in guinea-pig
      isolated bronchus that is dependent upon the activation of vanilloid receptors on
      airway sensory nerves. However, cannabinoid receptors do not appear to play a
      role in this regard, nor in regulating the release of neuropeptides from airway
      sensory nerves under physiological conditions.

PMID- 11226145
TI  - Effects of the endogenous opioid peptide, endomorphin 1, on supraoptic nucleus
      oxytocin and vasopressin neurones in vivo and in vitro.
AB  - We investigated the actions of the endogenous opioid tetra-peptide endomorphin 1,
      a selective mu-opioid receptor agonist, on oxytocin and vasopressin cell activity
      in vivo and in vitro. The activity of antidromically-identified supraoptic
      nucleus cells were recorded from urethane-anaesthetized female rats. The firing
      rates of both oxytocin and vasopressin cells were reduced by
      intracerebroventricular endomorphin 1 (5 - 100 pmol); this inhibition was
      prevented by intravenous naloxone (5 mg kg(-1)). A second group of rats was
      infused intracerebroventricularly with endomorphin 1 (27 pmol min(-1)) over 5
      days. The firing rates of oxytocin and vasopressin cells in endomorphin 1 pre
      treated rats were similar to those of endomorphin 1 naive rats, indicating
      tolerance to the inhibitory effects of endomorphin 1. Intravenous naloxone
      induced similar modest and transient increases in the firing rate of oxytocin
      cells in endomorphin 1 pre-treated rats and endomorphin 1 naive rats, indicating
      that endomorphin 1, unlike the mu-opioid alkaloid agonist, morphine, does not
      induce mu-opioid dependence in these cells. In vitro, whole-cell current clamp
      recordings were made from supraoptic nucleus cells in superfused coronal
      hypothalamic slices from young female rats. Endomorphin 1 (100 nM) inhibited the
      firing rate of oxytocin cells but had no significant effect on vasopressin cells
      at up to 10 microM. Inhibition of oxytocin cells was reversed by naloxone, and
      remained when synaptic transmission was blocked by superfusion with low
      Ca(2+)/Co(2+)-containing medium. Thus, endomorphin 1 directly inhibits oxytocin
      cells but inhibits vasopressin cells by indirect actions. Chronic endomorphin 1
      administration induces mu-opioid tolerance in oxytocin and vasopressin cells but
      not mu-opioid dependence in oxytocin cells.

PMID- 11226146
TI  - Pharmacological evidence for CGRP uptake into perivascular capsaicin sensitive
      nerve terminals.
AB  - Specific mechanisms, providing reuptake of cathecholamine and amino acid
      neurotransmitters (e.g. serotonin and glutamate) into cells of the central
      nervous system are well known, whereas neuronal uptake of neuropeptide
      transmitters have not previously been reported. In the present study we present
      evidence for uptake of the 37 amino acid neuropeptide, calcitonin gene-related
      peptide (CGRP) into perivascular terminals of capsaicin sensitive nerve fibres,
      innervating the guinea-pig basilar artery. Release of CGRP from perivascular
      nerve terminals was obtained by capsaicin-induced vanilloid receptor-stimulation
      and detected as CGRP receptor-mediated dilation of isolated segments of the
      guinea-pig basilar artery. Following three repeated capsaicin challenges, CGRP
      depleted segments were incubated with CGRP. This caused significant reappearance
      of capsaicin-induced vasodilatory responses. These responses were dependent on
      duration and concentration of the preceding CGRP incubation and were inhibited by
      the CGRP receptor antagonist, CGRP(8 - 37). The CGRP-re-depletion was
      significantly reduced when CGRP(8 - 37) was present during the preceding CGRP
      incubation. Thus, presynaptic CGRP receptors are likely to be involved in
      neuronal CGRP uptake. Incubating the artery segments with (125)I-CGRP allowed
      subsequent detection of capsaicin-induced (125)I-release. Immunohistochemical
      experiments showed that only terminal CGRP is subject to capsaicin-induced
      depletion in vitro, whereas CGRP-immunoreactivity endures in the nerve fibres.

PMID- 11226147
TI  - Effects of KRN2391 on ionic currents in rabbit femoral arterial myocytes.
AB  - The effects of KRN2391, an ATP-sensitive K+ channel opener (KCO) which also acts
      as a nitrate, on ionic membrane currents in rabbit femoral arterial myocytes were
      examined. Under whole-cell clamp conditions where cells were superfused with
      physiological salts solution containing 5.9 mM K+, KRN2391 elicited an outward
      current at a holding potential of -30 mV. KRN2391-induced current had a reversal
      potential of -78 mV and was abolished by glibenclamide (glib). KRN2391 was
      approximately 25 times more potent than nicorandil to activate an ATP-sensitive
      K+ current (I:(KATP)). On the other hand, 10 microM KRN2391 did not affect either
      voltage-dependent Ca(2+) or delayed rectifier K+ channel currents. In the inside
      out patch configuration, KRN2391 activated 47 pS K+ channels in the presence of
      nucleotide diphosphates (NDPs) under the symmetrical 140 mM K+ conditions. Glib
      and intracellular ATP reversibly inhibited the activity of the 47 pS K+ channels.
      The 47 pS K+ channels activated by KRN2391 are similar in their conductance and
      other properties to NDP-sensitive K+ channels (K(NDP) channels) described in
      other smooth muscles and the cloned channels. KRN2391 is a potent activator of
      the 47 pS K+ channels and the activation can contribute to the KRN2391-induced
      vasodilation in arterial muscles.

PMID- 11226149
TI  - The black cat/white cat principle of signal integration in bacterial promoters.

PMID- 11226150
TI  - CD81 extracellular domain 3D structure: insight into the tetraspanin superfamily
      structural motifs.
AB  - Human CD81, a known receptor for hepatitis C virus envelope E2 glycoprotein, is a
      transmembrane protein belonging to the tetraspanin family. The crystal structure
      of human CD81 large extracellular domain is reported here at 1.6 A resolution.
      Each subunit within the homodimeric protein displays a mushroom-like structure,
      composed of five alpha-helices arranged in 'stalk' and 'head' subdomains.
      Residues known to be involved in virus binding can be mapped onto the head
      subdomain, providing a basis for the design of antiviral drugs and vaccines.
      Sequence analysis of 160 tetraspanins indicates that key structural features and
      the new protein fold observed in the CD81 large extracellular domain are
      conserved within the family. On these bases, it is proposed that tetraspanins may
      assemble at the cell surface into homo- and/or hetero-dimers through a conserved
      hydrophobic interface located in the stalk subdomain, while interacting with
      other liganding proteins, including hepatitis C virus E2, through the head
      subdomain. The topology of such interactions provides a rationale for the
      assembly of the so-called tetraspan-web.

PMID- 11226151
TI  - The fusion domain of HIV gp41 interacts specifically with heparan sulfate on the
      T-lymphocyte cell surface.
AB  - Studies of the interaction of the 16 residue fusion peptide domain of human
      immunodeficiency virus glycoprotein gp41 (gp41(FD)) with T lymphocytes are
      outlined. Fluorescence measurements of changes in the electrostatic surface and
      dipole potentials of the plasma membrane following the interaction with gp41(FD)
      are described. The results show that gp41(FD) interacts with heparan sulfate
      located on the cell surface. This interaction is blocked by interleukin-8 and
      abolished by pre-treating the cells with heparitinase. The specificity of the
      reaction was also assessed by observations that soluble heparan sulfate competes
      with the cell membrane interaction whereas soluble heparin (at the levels
      utilized) does not. Following binding to heparan sulfate, the interaction with
      the membrane seems to take place in a cooperative manner with the formation of
      gp41(FD) trimers. In simpler phospholipid membranes, however, a trimeric complex
      does not appear to be the dominant mode of interaction. Finally, by repeating
      some of these studies within an imaging regime, it appears that the gp41(FD)-T
      cell interaction takes place within specific domains on the cell surface to
      similarly localized heparan sulfate moieties.

PMID- 11226153
TI  - Structure of a genetically engineered molecular motor.
AB  - Molecular motors move unidirectionally along polymer tracks, producing movement
      and force in an ATP-dependent fashion. They achieve this by amplifying small
      conformational changes in the nucleotide-binding region into force-generating
      movements of larger protein domains. We present the 2.8 A resolution crystal
      structure of an artificial actin-based motor. By combining the catalytic domain
      of myosin II with a 130 A conformational amplifier consisting of repeats 1 and 2
      of alpha-actinin, we demonstrate that it is possible to genetically engineer
      single-polypeptide molecular motors with precisely defined lever arm lengths and
      specific motile properties. Furthermore, our structure shows the consequences of
      mutating a conserved salt bridge in the nucleotide-binding region. Disruption of
      this salt bridge, which is known to severely inhibit ATP hydrolysis activity,
      appears to interfere with formation of myosin's catalytically active 'closed'
      conformation. Finally, we describe the structure of alpha-actinin repeats 1 and 2
      as being composed of two rigid, triple-helical bundles linked by an uninterrupted
      alpha-helix. This fold is very similar to the previously described structures of
      alpha-actinin repeats 2 and 3, and alpha-spectrin repeats 16 and 17.

PMID- 11226152
TI  - Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in
      GSK-3beta conditional transgenic mice.
AB  - Glycogen synthase kinase-3beta (GSK-3beta) has been postulated to mediate
      Alzheimer's disease tau hyperphosphorylation, beta-amyloid-induced neurotoxicity
      and presenilin-1 mutation pathogenic effects. By using the tet-regulated system
      we have produced conditional transgenic mice overexpressing GSK-3beta in the
      brain during adulthood while avoiding perinatal lethality due to embryonic
      transgene expression. These mice show decreased levels of nuclear beta-catenin
      and hyperphosphorylation of tau in hippocampal neurons, the latter resulting in
      pretangle-like somatodendritic localization of tau. Neurons displaying
      somatodendritic localization of tau often show abnormal morphologies and
      detachment from the surrounding neuropil. Reactive astrocytosis and microgliosis
      were also indicative of neuronal stress and death. This was further confirmed by
      TUNEL and cleaved caspase-3 immunostaining of dentate gyrus granule cells. Our
      results demonstrate that in vivo overexpression of GSK-3beta results in
      neurodegeneration and suggest that these mice can be used as an animal model to
      study the relevance of GSK-3beta deregulation to the pathogenesis of Alzheimer's
      disease.

PMID- 11226154
TI  - The endocannabinoid anandamide is a direct and selective blocker of the
      background K(+) channel TASK-1.
AB  - TASK-1 encodes an acid- and anaesthetic-sensitive background K(+) current, which
      sets the resting membrane potential of both cerebellar granule neurons and
      somatic motoneurons. We demonstrate that TASK-1, unlike the other two pore (2P)
      domain K(+) channels, is directly blocked by submicromolar concentrations of the
      endocannabinoid anandamide, independently of the CB1 and CB2 receptors. In
      cerebellar granule neurons, anandamide also blocks the TASK-1 standing-outward
      K(+) current, IKso, and induces depolarization. Anandamide-induced
      neurobehavioural effects are only partly reversed by antagonists of the
      cannabinoid receptors, suggesting the involvement of alternative pathways. TASK-1
      constitutes a novel sensitive molecular target for this endocannabinoid.

PMID- 11226155
TI  - A plasma membrane-type Ca(2+)-ATPase co-localizes with a vacuolar H(+)
      pyrophosphatase to acidocalcisomes of Toxoplasma gondii.
AB  - Ca(2+)-ATPases are likely to play critical roles in the biochemistry of
      Toxoplasma gondii, since these protozoa are obligate intracellular parasites and
      the Ca(2+) concentration in their intracellular location is three orders of
      magnitude lower than in the extracellular medium. Here, we report the cloning and
      sequencing of a gene encoding a plasma membrane-type Ca(2+)-ATPase (PMCA) of
      T.gondii (TgA1). The predicted protein (TgA1) exhibits 32-36% identity to
      vacuolar Ca(2+)-ATPases of Trypanosoma cruzi, Saccharomyces cerevisiae, Entamoeba
      histolytica and Dictyostelium discoideum. Sequencing of both cDNA and genomic DNA
      from T.gondii indicated that TgA1 contains two introns near the C-terminus. A
      hydropathy profile of the protein suggests 10 transmembrane domains. TgA1
      suppresses the Ca(2+) hypersensitivity of a mutant of S.cerevisiae that has a
      defect in vacuolar Ca(2+) accumulation. Indirect immunofluorescence and
      immunoelectron microscopy analysis indicate that TgA1 localizes to the plasma
      membrane and co-localizes with the vacuolar H(+)-pyrophosphatase to intracellular
      vacuoles identified morphologically and by X-ray microanalysis as the
      acidocalcisomes. This vacuolar-type Ca(2+)-ATPase could play an important role in
      Ca(2+) homeostasis in T.gondii.

PMID- 11226156
TI  - Role of elementary Ca(2+) puffs in generating repetitive Ca(2+) oscillations.
AB  - Inositol (1,4,5)-trisphosphate (IP(3)) liberates intracellular Ca(2+) both as
      localized 'puffs' and as repetitive waves that encode information in a frequency
      dependent manner. Using video-rate confocal imaging, together with photorelease
      of IP(3) in Xenopus oocytes, we investigated the roles of puffs in determining
      the periodicity of global Ca(2+) waves. Wave frequency is not delimited solely by
      cyclical recovery of the cell's ability to support wave propagation, but further
      involves sensitization of Ca(2+)-induced Ca(2+) release by progressive increases
      in puff frequency and amplitude at numerous sites during the interwave period,
      and accumulation of pacemaker Ca(2+), allowing a puff at a 'focal' site to
      trigger a subsequent wave. These specific 'focal' sites, distinguished by their
      higher sensitivity to IP(3) and close apposition to neighboring puff sites,
      preferentially entrain both the temporal frequency and spatial directionality of
      Ca(2+) waves. Although summation of activity from many stochastic puff sites
      promotes the generation of regularly periodic global Ca(2+) signals, the
      properties of individual Ca(2+) puffs control the kinetics of Ca(2+) spiking and
      the (higher) frequency of subcellular spikes in their local microdomain.

PMID- 11226157
TI  - The projection structure of EmrE, a proton-linked multidrug transporter from
      Escherichia coli, at 7 A resolution.
AB  - EmrE belongs to a family of eubacterial multidrug transporters that confer
      resistance to a wide variety of toxins by coupling the influx of protons to toxin
      extrusion. EmrE was purified and crystallized in two dimensions by reconstitution
      with dimyristoylphosphatidylcholine into lipid bilayers. Images of frozen
      hydrated crystals were collected by cryo-electron microscopy and a projection
      structure of EmrE was calculated to 7 A resolution. The projection map shows an
      asymmetric EmrE dimer with overall dimensions approximately 31 x 40 A, comprising
      an arc of highly tilted helices separating two helices nearly perpendicular to
      the membrane from another two helices, one tilted and the other nearly
      perpendicular. There is no obvious 2-fold symmetry axis perpendicular to the
      membrane within the dimer, suggesting that the monomers may have different
      structures in the functional unit.

PMID- 11226158
TI  - Specificity of Cdk activation in vivo by the two Caks Mcs6 and Csk1 in fission
      yeast.
AB  - Activating phosphorylation of cyclin-dependent kinases (Cdks) is mediated by at
      least two structurally distinct types of Cdk-activating kinases (Caks): the
      trimeric Cdk7-cyclin H-Mat1 complex in metazoans and the single-subunit Cak1 in
      budding yeast. Fission yeast has both Cak types: Mcs6 is a Cdk7 ortholog and Csk1
      a single-subunit kinase. Both phosphorylate Cdks in vitro and rescue a
      thermosensitive budding yeast CAK1 strain. However, this apparent redundancy is
      not observed in fission yeast in vivo. We have identified mutants that exhibit
      phenotypes attributable to defects in either Mcs6-activating phosphorylation or
      in Cdc2-activating phosphorylation. Mcs6, human Cdk7 and budding yeast Cak1 were
      all active as Caks for Cdc2 when expressed in fission yeast. Although Csk1 could
      activate Mcs6, it was unable to activate Cdc2. Biochemical experiments supported
      these genetic results: budding yeast Cak1 could bind and phosphorylate Cdc2 from
      fission yeast lysates, whereas fission yeast Csk1 could not. These results
      indicate that Mcs6 is the direct activator of Cdc2, and Csk1 only activates Mcs6.
      This demonstrates in vivo specificity in Cdk activation by Caks.

PMID- 11226159
TI  - Specificity of signaling by STAT1 depends on SH2 and C-terminal domains that
      regulate Ser727 phosphorylation, differentially affecting specific target gene
      expression.
AB  - Complete activation of signal transducer and activator of transcription 1 (STAT1)
      requires phosphorylation at both Y701 and a conserved PMS(727)P sequence. S727
      phosphorylation of STAT1 in interferon-gamma (IFN-gamma)-treated mouse
      fibroblasts occurred without a need for p38 mitogen-activated protein kinase
      (MAPK), extracellular signal-regulated kinases 1 and 2 or c-Jun kinases, and
      required both an intact SH2 domain and phosphorylation of Y701. In contrast, UV
      irradiation-induced STAT1 phosphorylation on S727 required p38MAPK, but no SH2
      domain- phosphotyrosine interactions. Mutation of S727 differentially affected
      IFN-gamma target genes, at the level of both basal and induced expression.
      Particularly strong effects were noted for the GBP1 and TAP1 genes. The PMS(727)P
      motif of STAT3 was phosphorylated by stimuli and signaling pathways different
      from those for STAT1 S727. Transfer of the STAT3 C-terminus to STAT1 changed the
      stimulus and pathway specificity of STAT1 S727 phosphorylation to that of STAT3.
      Our data suggest that STAT C-termini contribute to the specificity of cellular
      responses by linking individual STATs to different serine kinase pathways and
      through an intrinsically different requirement for serine phosphorylation at
      different target gene promoters.

PMID- 11226160
TI  - Coiled-coil domain-mediated FRQ-FRQ interaction is essential for its circadian
      clock function in Neurospora.
AB  - The frequency (frq) gene, the central component of the frq-based circadian
      negative feedback loop, regulates various aspects of the circadian clock in
      NEUROSPORA: However, the biochemical function of its protein products, FRQ, is
      poorly understood. In this study, we demonstrated that the most conserved region
      of FRQ forms a coiled-coil domain. FRQ interacts with itself in vivo, and the
      deletion of the coiled-coil region results in loss of the interaction. Point
      mutations, which are designed to disrupt the coiled-coil structure, weaken or
      completely abolish the FRQ self-association and lead to the arrhythmicity of the
      overt rhythm. Mutations of the FRQ coiled-coil that inhibit self-association also
      prevent its interaction with two other key components of the NEUROSPORA:
      circadian clock, namely WC-1 and WC-2, the two PAS domain-containing
      transcription factors. Taken together, these data strongly suggest that the
      formation of the FRQ-FRQ and FRQ-WC complexes is essential for the function of
      the NEUROSPORA: clock.

PMID- 11226161
TI  - WC-2 mediates WC-1-FRQ interaction within the PAS protein-linked circadian
      feedback loop of Neurospora.
AB  - Eukaryotic circadian clocks comprise feedback loops where PAS domain-containing
      transcriptional activators drive gene expression of negative elements. In
      NEUROSPORA:, clock models posit a White Collar complex (WCC) containing WC-1 and
      WC-2 that activates expression of the central clock gene frequency (frq); FRQ
      protein is hypothesized to feed back to block the activity of the WCC. We have
      characterized the WC-2 protein and its role in this complex: WC-2 is an abundant
      constitutive nuclear protein, in contrast to rhythmically expressed FRQ and WC-1.
      WC-2 interacts with WC-1 and FRQ but, significantly, WC-1 and FRQ do not interact
      in the absence of WC-2. By quantifying the relative numbers of WC-2, FRQ and WC-1
      proteins and complexes in cell extracts, both the numbers and types of complexes
      at different circadian times were estimated, yielding results consistent with the
      model. Constitutive and abundant WC-2 appears to provide a scaffold allowing for
      the interaction of two limiting and rhythmically out-of-phase proteins, FRQ and
      WC-1, and this temporal and physical relationship may be responsible for rhythmic
      expression of frq.

PMID- 11226162
TI  - Identification of a structural motif that confers specific interaction with the
      WD40 repeat domain of Arabidopsis COP1.
AB  - Arabidopsis COP1 is a photomorphogenesis repressor capable of directly
      interacting with the photomorphogenesis-promoting factor HY5. This interaction
      between HY5 and COP1 results in targeted deg radation of HY5 by the 26S
      proteasome. Here we characterized the WD40 repeat domain-mediated interactions of
      COP1 with HY5 and two new proteins. Mutational analysis of those interactive
      partners revealed a conserved motif responsible for the interaction with the WD40
      domain. This novel motif, with the core sequence V-P-E/D-&phi;-G (&phi; =
      hydrophobic residue) in conjunction with an upstream stretch of 4-5 negatively
      charged residues, interacts with a defined surface area of the ss-propeller
      assembly of the COP1 WD40 repeat domain through both hydrophobic and ionic
      interactions. Several residues in the COP1 WD40 domain that are critical for the
      interaction with this motif have been revealed. The fact that point mutations
      either in the COP1 WD40 domain or in the HY5 motif that abolish the interaction
      between COP1 and HY5 in yeast result in a dramatic reduction of HY5 degradation
      in transgenic plants validates the biological significance of this defined
      interaction.

PMID- 11226163
TI  - Epidermal growth factor signaling via Ras controls the Smad transcriptional co
      repressor TGIF.
AB  - Smad transcription factors mediate the actions of transforming growth factor-beta
      (TGF-beta) cytokines during development and tissue homeostasis. TGF-beta receptor
      activated Smad2 regulates gene expression by associating with transcriptional co
      activators or co-repressors. The Smad co-repressor TGIF competes with the co
      activator p300 for Smad2 association, such that TGIF abundance helps determine
      the outcome of a TGF-beta response. Small alterations in the physiological levels
      of TGIF can have profound effects on human development, as shown by the
      devastating brain and craniofacial developmental defects in heterozygotes
      carrying a hypomorphic TGIF mutant allele. Here we show that TGIF levels modulate
      sensitivity to TGF-beta-mediated growth inhibition, that TGIF is a short-lived
      protein and that epidermal growth factor (EGF) signaling via the Ras-Mek pathway
      causes the phosphorylation of TGIF at two Erk MAP kinase sites, leading to TGIF
      stabilization and favoring the formation of Smad2-TGIF co-repressor complexes in
      response to TGF-beta. These results identify the first mechanism for regulating
      TGIF levels and suggest a potential link for Smad and Ras pathway convergence at
      the transcriptional level.

PMID- 11226164
TI  - Teashirt is required for transcriptional repression mediated by high Wingless
      levels.
AB  - During development, extracellular signals often act at multiple thresholds to
      specify distinct transcriptional and cellular responses. For example, in the
      embryonic midgut of Drosophila, low Wingless levels stimulate the transcription
      of homeotic genes whereas high Wingless levels repress these genes. Wingless-
      mediated transcriptional activation is conferred by Drosophila: T-cell factor
      (dTCF) and its co-activator Armadillo, but the nuclear factors mediating
      transcriptional repression are unknown. Here we show that teashirt is required
      for Wingless-mediated repression of Ultrabithorax: in the midgut. Teashirt is
      also a repressor of the homeotic gene labial in this tissue. Furthermore, the
      target sequence for Tsh within the Ultrabithorax: midgut enhancer coincides with
      the response sequence for Wingless-mediated repression. Finally, we demonstrate
      that the zinc finger protein Teashirt behaves as a transcriptional repressor in
      transfected mammalian cells. It thus appears that the response to high Wingless
      levels in the Drosophila: midgut is indirect and based on transcriptional
      activation of the Teashirt repressor.

PMID- 11226165
TI  - A thermostable platform for transcriptional regulation: the DNA-binding
      properties of two Lrp homologs from the hyperthermophilic archaeon Methanococcus
      jannaschii.
AB  - The hyperthermophilic archaeon Methanococcus jannaschii encodes two putative
      transcription regulators, Ptr1 and Ptr2, related to the bacterial Lrp/AsnC family
      of transcriptional regulators. We show that these two small helix-turn-helix
      proteins are specific DNA-binding proteins recognizing sites in their respective
      promoter regions. In vitro selection at high temperature has been used to isolate
      sets of high- affinity DNA sites that define a palindromic consensus binding
      sequence for each protein. Ptr1 and Ptr2 bind these cognate sites from one side
      of the DNA helix, as dimers, with each protein monomer making base- specific
      contacts in the major groove. As the first archaeal DNA-binding proteins with
      clearly defined specificities, Ptr1 and Ptr2 provide a thermostable DNA-binding
      platform for analysis of effector interactions with the core archaeal
      transcription apparatus; a platform allowing manipulation of promoter structure
      and examination of mechanisms of action at heterologous promoters.

PMID- 11226166
TI  - Analysis of the mechanism of action of non-deletion hereditary persistence of
      fetal hemoglobin mutants in transgenic mice.
AB  - Transgenic mice carrying an (A)gamma gene construct containing a -382 5'
      truncation of the (A)gamma gene promoter have a phenotype of hereditary
      persistence of fetal hemoglobin (HPFH) but, when the CACCC box of the 
      382(A)gamma promoter is deleted, there is no gamma gene expression in the adult
      mice. We used this system to investigate the mechanism whereby human HPFH
      mutations result in gamma gene expression in the adult. Introduction of the -198
      T-->C HPFH mutation into the CACCC-less (A)gamma gene construct re-established
      the HPFH phenotype, indicating that this mutation increases promoter strength,
      most probably by establishing a novel CACCC box sequence in the -198(A)gamma
      region. The HPFH phenotype was also re-established when the -117 C-->T HPFH
      mutation was introduced into a -141(A)gamma promoter with a destroyed CACCC box,
      indicating that this mutation increases gamma promoter strength in the absence of
      the CACCC motif. The T-->A -175 HPFH mutation failed to re-establish the HPFH
      phenotype when the CACCC box was deleted, indicating that gamma gene expression
      in this mutation is CACCC box dependent. These results provide the first in vivo
      experimental evidence in support of mechanistic heterogeneity of the non-deletion
      HPFH mutants.

PMID- 11226167
TI  - Solution structure of the PHD domain from the KAP-1 corepressor: structural
      determinants for PHD, RING and LIM zinc-binding domains.
AB  - Plant homeodomain (PHD) domains are found in >400 eukaryotic proteins, many of
      which are transcriptional regulators. Naturally occurring point mutations or
      deletions of this domain contribute to a variety of human diseases, including
      ATRX syndrome, myeloid leukemias and autoimmune dysfunction. Here we report the
      first structural characterization of a PHD domain. Our studies reveal that the
      PHD domain from KAP-1 corepressor binds zinc in a cross-brace topology between
      anti-parallel ss-strands reminiscent of RING (really interesting new gene)
      domains. Using a mutational analysis, we define the structural features required
      for transcriptional repression by KAP-1 and explain naturally occurring, disease
      causing mutations in PHD domains of other proteins. From a comparison of this PHD
      structure with previously reported RING and LIM (Lin11/Isl-1/Mec-3) structures,
      we infer sequence determinants that allow discrimination among PHD, RING and LIM
      motifs.

PMID- 11226168
TI  - Structure-based design of a dimeric RNA-peptide complex.
AB  - The arginine-rich RNA-binding domain of bovine immunodeficiency virus (BIV) Tat
      adopts a beta-hairpin conformation upon binding to the major groove of BIV TAR.
      Based on its NMR structure, we modeled dimeric arrangements in which two adjacent
      TAR sites might be recognized with high affinity by a dimeric peptide. Some
      dimeric RNAs efficiently bound two unlinked BIV Tat peptides in vitro, but could
      not bind even one monomeric peptide in vivo, as monitored by transcriptional
      activation of human immunodeficiency virus long terminal repeat reporters.
      Results with additional reporters suggest that extending the RNA helix in the
      dimeric arrangements inhibits peptide binding by decreasing major groove
      accessibility. In contrast, a dimeric peptide efficiently bound an optimally
      arranged dimeric TAR in vivo, and bound with an affinity at least 10-fold higher
      than the monomeric peptide in vitro. Mutating specific nucleotides in each RNA
      'half-site' or specific amino acids in each beta-hairpin of the dimeric peptide
      substantially decreased binding affinity, providing evidence for the modeled
      dimer-dimer interaction. These studies provide a starting point for identifying
      dimeric RNA-protein interactions with even higher binding affinities and
      specificities.

PMID- 11226169
TI  - Sm protein-Sm site RNA interactions within the inner ring of the spliceosomal
      snRNP core structure.
AB  - Seven Sm proteins, E, F, G, D1, D2, D3 and B/B', assemble in a stepwise manner
      onto the single-stranded Sm site element (PuAU(4-6)GPu) of the U1, U2, U4 and U5
      spliceosomal snRNAs, resulting in a doughnut-shaped core RNP structure. Here we
      show by UV cross-linking experiments using an Sm site RNA oligonucleotide
      (AAUUUUUGA) that several Sm proteins contact the Sm site RNA, with the most
      efficient cross-links observed for the G and B/B' proteins. Site-specific photo
      cross-linking revealed that the G and B/B' proteins contact distinct uridines (in
      the first and third positions, respectively) in a highly position-specific
      manner. Amino acids involved in contacting the RNA are located at equivalent
      regions in both proteins, namely in loop L3 of the Sm1 motif, which has been
      predicted to jut into the hole of the Sm ring. Our results thus provide the first
      evidence that, within the core snRNP, multiple Sm protein-Sm site RNA contacts
      occur on the inner surface of the heptameric Sm protein ring.

PMID- 11226170
TI  - A cytosolic NAD-dependent deacetylase, Hst2p, can modulate nucleolar and
      telomeric silencing in yeast.
AB  - In budding yeast, the silent information regulator Sir2p is a nuclear NAD
      dependent deacetylase that is essential for both telomeric and rDNA silencing.
      All eukaryotic species examined to date have multiple homologues of Sir two
      (HSTs), which share a highly conserved globular core domain. Here we report that
      yeast Hst2p and a mammalian Hst2p homologue, hSirT2p, are cytoplasmic in yeast
      and human cells, in contrast to yHst1p and ySir2p which are exclusively nuclear.
      Although yHst2p cannot restore silencing in a sir2 deletion, overexpression of
      yHst2p influences nuclear silencing events in a SIR2 strain, derepressing
      subtelomeric silencing while increasing repression in the rDNA. In contrast, a
      form of ySir2p carrying a point mutation in the conserved core domain disrupts
      both telomeric position effect (TPE) and rDNA repression at low expression
      levels. This argues that non-nuclear yHst2p can compete for a substrate or ligand
      specifically required for telomeric, and not rDNA repression.

PMID- 11226171
TI  - Novel functional requirements for non-homologous DNA end joining in
      Schizosaccharomyces pombe.
AB  - DNA double strand break (DSB) repair by non-homologous end joining (NHEJ) in
      mammalian cells requires the Ku70-Ku80 heterodimer, the DNA-PK catalytic subunit
      DNA-PKcs, as well as DNA ligase IV and Xrcc4. NHEJ of plasmid DSBs in
      Saccharomyces cerevisiae requires Ku, Xrcc4 and DNA ligase IV, as well as Mre11,
      Rad50, Xrs2 and DNA damage checkpoint proteins. Saccharomyces cerevisiae Ku is
      also required for telomere length maintenance and transcriptional silencing. We
      have characterized NHEJ in Schizosaccharomyces pombe using an extrachromosomal
      assay and find that, as anticipated, it is Ku70 and DNA ligase IV dependent.
      Unexpectedly, we find that Rad32, Rad50 (the S.pombe homologues of Mre11 and
      Rad50, respectively) and checkpoint proteins are not required for NHEJ.
      Furthermore, although S.pombe Ku70 is required for maintenance of telomere
      length, it is dispensable for transcriptional silencing at telomeres and is
      located throughout the nucleus rather than concentrated at the telomeres.
      Together, these results provide insight into the mechanism of NHEJ and contrast
      significantly with recent studies in S.cerevisiae.

PMID- 11226172
TI  - Reconstitution of Epstein-Barr virus-based plasmid partitioning in budding yeast.
AB  - The EBNA1 protein of Epstein-Barr virus (EBV) mediates the partitioning of EBV
      episomes and EBV-based plasmids during cell division by a mechanism that appears
      to involve binding to the cellular EBP2 protein on human chromosomes. We have
      investigated the ability of EBNA1 and the EBV segregation element (FR) to mediate
      plasmid partitioning in Saccharomyces cerevisiae. EBNA1 expression alone did not
      enable the stable segregation of FR-containing plasmids in yeast, but segregation
      was rescued by human EBP2. The reconstituted segregation system required EBNA1,
      human EBP2 and the FR element, and functionally replaced a CEN element. An EBP2
      binding mutant of EBNA1 and an EBNA1 binding mutant of EBP2 each failed to
      support FR-plasmid partitioning, indicating that an EBNA1-EBP2 interaction is
      required. The results provide direct evidence of the role of hEBP2 in EBNA1
      mediated segregation and demonstrate that heterologous segregation systems can be
      reconstituted in yeast.

PMID- 11226173
TI  - A primordial tRNA modification required for the evolution of life?
AB  - The evolution of reading frame maintenance must have been an early event, and
      presumably preceded the emergence of the three domains Archaea, Bacteria and
      Eukarya. Features evolved early in reading frame maintenance may still exist in
      present-day organisms. We show that one such feature may be the modified
      nucleoside 1-methylguanosine (m(1)G37), which prevents frameshifting and is
      present adjacent to and 3' of the anticodon (position 37) in the same subset of
      tRNAs from all organisms, including that with the smallest sequenced genome
      (Mycoplasma genitalium), and organelles. We have identified the genes encoding
      the enzyme tRNA(m(1)G37)methyltransferase from all three domains. We also show
      that they are orthologues, and suggest that they originated from a primordial
      gene. Lack of m(1)G37 severely impairs the growth of a bacterium and a eukaryote
      to a similar degree. Yeast tRNA(m(1)G37)methyltransferase also synthesizes 1
      methylinosine and participates in the formation of the Y-base (yW). Our results
      suggest that m(1)G37 existed in tRNA before the divergence of the three domains,
      and that a tRNA(m(1)G37)methyltrans ferase is part of the minimal set of gene
      products required for life.

PMID- 11226174
TI  - Effects of poliovirus infection on nucleo-cytoplasmic trafficking and nuclear
      pore complex composition.
AB  - Infection of eukaryotic cells with lytic RNA viruses results in extensive
      interactions of viral gene products with macromolecular pathways of the host,
      ultimately leading to death of the infected cells. We show here that infection of
      cells with poliovirus results in the cytoplasmic accumulation of a variety of
      shuttling and non-shuttling nuclear proteins that use multiple nuclear import
      pathways. In vitro nuclear import assays using semi-permeabilized infected cells
      confirmed that nuclear import was blocked and demonstrated that docking of
      nuclear import receptor-cargo complexes at the cytoplasmic face of the nuclear
      pore complex (NPC) was prevented. Analysis of components of the NPC revealed that
      two proteins, Nup153 and p62, were proteolyzed during poliovirus infection. These
      results suggest that the cytoplasmic relocalization of numerous cellular proteins
      is caused by the inhibition of multiple nuclear import pathways via alterations
      in NPC composition in poliovirus-infected cells. Blocking of nuclear import
      points to a novel strategy by which cytoplasmic RNA viruses can evade host immune
      defenses, by preventing signal transduction to the nucleus.

PMID- 11226175
TI  - PIG-M transfers the first mannose to glycosylphosphatidylinositol on the lumenal
      side of the ER.
AB  - Glycosylphosphatidylinositol (GPI) acts as a membrane anchor of many cell surface
      proteins. Its structure and biosynthetic pathway are generally conserved among
      eukaryotic organisms, with a number of differences. In particular, mammalian and
      protozoan mannosyltransferases needed for addition of the first mannose (GPI-MT
      I) have different substrate specificities and are targets of species- specific
      inhibitors of GPI biosynthesis. GPI-MT-I, however, has not been molecularly
      characterized. Characterization of GPI-MT-I would also help to clarify the
      topology of GPI biosynthesis. Here, we report a human cell line defective in GPI
      MT-I and the gene responsible, PIG-M. PIG-M encodes a new type of
      mannosyltransferase of 423 amino acids, bearing multiple transmembrane domains.
      PIG-M has a functionally important DXD motif, a characteristic of many
      glycosyltransferases, within a domain facing the lumen of the endoplasmic
      reticulum (ER), indicating that transfer of the first mannose to GPI occurs on
      the lumenal side of the ER membrane.

PMID- 11226176
TI  - Sec63p and Kar2p are required for the translocation of SRP-dependent precursors
      into the yeast endoplasmic reticulum in vivo.
AB  - The translocation of secretory polypeptides into the endoplasmic reticulum (ER)
      occurs at the translocon, a pore-forming structure that orchestrates the
      transport and maturation of polypeptides at the ER membrane. In yeast, targeting
      of secretory precursors to the translocon can occur by two distinct pathways that
      are distinguished by their dependence upon the signal recognition particle (SRP).
      The SRP-dependent pathway requires SRP and its membrane-bound receptor, whereas
      the SRP-independent pathway requires a separate receptor complex consisting of
      Sec62p, Sec63p, Sec71p, Sec72p plus lumenal Kar2p/BiP. Here we demonstrate that
      Sec63p and Kar2p are also required for the SRP-dependent targeting pathway in
      vivo. Furthermore, we demonstrate multiple roles for Sec63p, at least one of
      which is exclusive to the SRP-independent pathway.

PMID- 11226177
TI  - A novel clathrin homolog that co-distributes with cytoskeletal components
      functions in the trans-Golgi network.
AB  - A clathrin homolog encoded on human chromosome 22 (CHC22) displays distinct
      biochemistry, distribution and function compared with conventional clathrin heavy
      chain (CHC17), encoded on chromosome 17. CHC22 protein is upregulated during
      myoblast differentiation into myotubes and is expressed at high levels in muscle
      and at low levels in non-muscle cells, relative to CHC17. The trimeric CHC22
      protein does not interact with clathrin heavy chain subunits nor bind
      significantly to clathrin light chains. CHC22 associates with the AP1 and AP3
      adaptor complexes but not with AP2. In non-muscle cells, CHC22 localizes to
      perinuclear vesicular structures, the majority of which are not clathrin coated.
      Treatments that disrupt the actin-myosin cytoskeleton or affect sorting in the
      trans-Golgi network (TGN) cause CHC22 redistribution. Overexpression of a
      subdomain of CHC22 induces altered distribution of TGN markers. Together these
      results implicate CHC22 in TGN membrane traffic involving the cytoskeleton.

PMID- 11226181
TI  - Plant development: from cell fate to organ formation.

PMID- 11226179
TI  - Structural basis for the inactivation of retinoblastoma tumor suppressor by SV40
      large T antigen.
AB  - Inactivation of the retinoblastoma (Rb) tumor suppressor by Simian virus 40
      (SV40) large T antigen is one of the central features of tumorigenesis induced by
      SV40. Both the N-terminal J domain and the LxCxE motif of large T antigen are
      required for inactivation of Rb. The crystal structure of the N-terminal region
      (residues 7-117) of SV40 large T antigen bound to the pocket domain of Rb reveals
      that large T antigen contains a four-helix bundle, and residues from helices
      alpha2 and alpha4 and from a loop containing the LxCxE motif participate in the
      interactions with Rb. The two central helices and a connecting loop in large T
      antigen have structural similarities with the J domains of the molecular
      chaperones DnaJ and HDJ-1, suggesting that large T antigen may use a chaperone
      mechanism for its biological function. However, there are significant differences
      between large T antigen and the molecular chaperones in other regions and these
      differences are likely to provide the specificity needed for large T antigen to
      inactivate Rb.

PMID- 11226178
TI  - The SurA periplasmic PPIase lacking its parvulin domains functions in vivo and
      has chaperone activity.
AB  - The Escherichia coli periplasmic peptidyl-prolyl isomerase (PPIase) SurA is
      involved in the maturation of outer membrane porins. SurA consists of a
      substantial N-terminal region, two iterative parvulin-like domains and a C
      terminal tail. Here we show that a variant of SurA lacking both parvulin-like
      domains exhibits a PPIase-independent chaperone-like activity in vitro and almost
      completely complements the in vivo function of intact SurA. SurA interacts
      preferentially (>50-fold) with in vitro synthesized porins over other similarly
      sized proteins, leading us to suggest that the chaperone-like function of SurA
      preferentially facilitates maturation of outer membrane proteins.

PMID- 11226183
TI  - Cytogenomic analyses reveal the structural plasticity of the chloroplast genome
      in higher plants.
AB  - A DNA fiber-based fluorescence in situ hybridization (fiber-FISH) technique was
      developed to analyze the structure and organization of a large number of intact
      chloroplast DNA (cpDNA) molecules from Arabidopsis, tobacco, and pea. Using this
      cytogenomic approach, we determined that 25 to 45% of the cpDNA within developing
      leaf tissue consists of circular molecules. Both linear and circular DNA fibers
      with one to four copies of the chloroplast genome were present, with monomers
      being the predominant structure. Arabidopsis and tobacco chloroplasts contained
      previously unidentified multimers (>900 kb) consisting of six to 10 genome
      equivalents. We further discovered rearranged cpDNA molecules of incomplete
      genome equivalents, confirmed by both differential hybridizations and size
      estimations. The unique cpDNA organization and novel structures revealed in this
      study demonstrate that higher plant cpDNA is more structurally plastic than
      previous sequence and electrophoretic analyses have suggested. Additionally, we
      demonstrate how the fiber-FISH-based cytogenomic approach allows for powerful
      analysis of very rare events that cannot be detected by traditional techniques
      such as DNA gel blot hybridization or polymerase chain reaction.

PMID- 11226182
TI  - Petunia Ap2-like genes and their role in flower and seed development.
AB  - We have isolated three Apetala2 (Ap2)-like genes from petunia and studied their
      expression patterns by in situ hybridization. PhAp2A has a high sequence
      similarity to the A function gene Ap2 from Arabidopsis and a similar expression
      pattern during flower development, suggesting that they are cognate orthologs.
      PhAp2B and PhAp2C encode for AP2-like proteins that belong to a different
      subgroup of the AP2 family of transcription factors and exhibit divergent, nearly
      complementary expression patterns during flower development compared with PhAp2A.
      In contrast, all three PhAp2 genes are strongly expressed in endosperm. The
      phenotype of the petunia A-type mutant blind cannot be attributed to mutations in
      the petunia Ap2 homologs identified in this study, and reverse genetics
      strategies applied to identify phap2a mutants indicate that PhAp2A might not be
      essential for normal perianth development in petunia. Nevertheless, we show that
      PhAp2A is capable of restoring the homeotic transformations observed in flowers
      and seed of the ap2-1 mutant of Arabidopsis. Although the interspecific
      complementation proves that PhAp2A encodes a genuine Ap2 ortholog from petunia,
      additional factors may be involved in the control of perianth identity in this
      species.

PMID- 11226184
TI  - Domain swapping and gene shuffling identify sequences required for induction of
      an Avr-dependent hypersensitive response by the tomato Cf-4 and Cf-9 proteins.
AB  - The tomato Cf-4 and Cf-9 genes confer resistance to infection by the biotrophic
      leaf mold pathogen Cladosporium. Their protein products induce a hypersensitive
      response (HR) upon recognition of the fungus-encoded Avr4 and Avr9 peptides. Cf-4
      and Cf-9 share >91% sequence identity and are distinguished by sequences in their
      N-terminal domains A and B, their N-terminal leucine-rich repeats (LRRs) in
      domain C1, and their LRR copy number (25 and 27 LRRs, respectively). Analysis of
      Cf-4/Cf-9 chimeras, using several different bioassays, has identified sequences
      in Cf-4 and Cf-9 that are required for the Avr-dependent HR in tobacco and
      tomato. A 10-amino acid deletion within Cf-4 domain B relative to Cf-9 was
      required for full Avr4-dependent induction of an HR in most chimeras analyzed.
      Additional sequences required for Cf-4 function are located in LRRs 11 and 12, a
      region that contains only eight of the 67 amino acids that distinguish it from Cf
      9. One chimera, with 25 LRRs that retained LRR 11 of Cf-4, induced an attenuated
      Avr4-dependent HR. The substitution of Cf-9 N-terminal LRRs 1 to 9 with the
      corresponding sequences from Cf-4 resulted in attenuation of the Avr9-induced HR,
      as did substitution of amino acid A433 in LRR 15. The amino acids L457 and K511
      in Cf-9 LRRs 16 and 18 are essential for induction of the Avr9-dependent HR.
      Therefore, important sequence determinants of Cf-9 function are located in LRRs
      10 to 18. This region contains 15 of the 67 amino acids that distinguish it from
      Cf-4, in addition to two extra LRRs. Our results demonstrate that sequence
      variation within the central LRRs of domain C1 and variation in LRR copy number
      in Cf-4 and Cf-9 play a major role in determining recognition specificity in
      these proteins.

PMID- 11226185
TI  - Identification of distinct specificity determinants in resistance protein Cf-4
      allows construction of a Cf-9 mutant that confers recognition of avirulence
      protein Avr4.
AB  - The tomato resistance genes Cf-4 and Cf-9 confer specific, hypersensitive
      response-associated recognition of Cladosporium carrying the avirulence genes
      Avr4 and Avr9, respectively. Cf-4 and Cf-9 encode type I transmembrane proteins
      with extracellular leucine-rich repeats (LRRs). Compared with Cf-9, Cf-4 lacks
      two LRRs and differs in 78 amino acid residues. To investigate the relevance of
      these differences for specificity, we exchanged domains between Cf-4 and Cf-9,
      and mutant constructs were tested for mediating the hypersensitive response by
      transient coexpression with either Avr4 or Avr9. We show that the number of LRRs
      is essential for both Cf-4 and Cf-9 function. In addition, Cf-9 specificity
      resides entirely in the LRR domain and appears to be distributed over several
      distant LRRs. In contrast, Cf-4 specificity determinants reside in the N-terminal
      LRR-flanking domain and three amino acid residues in LRRs 13, 14, and 16. These
      residues are present at putative solvent-exposed positions, and all are required
      for full Cf-4 function. Finally, we show that Cf-9 carrying the specificity
      determinants of Cf-4 has recognitional specificity for AVR4. The data indicate
      that diversifying selection of solvent-exposed residues has been a more important
      factor in the generation of Cf-4 specificity than has sequence exchange between
      Cf-4 progenitor genes. The fact that most variant residues in Cf-4 are not
      essential for Cf-4 specificity indicates that the diverse decoration of R
      proteins is not fully adapted to confer recognition of a certain avirulence
      determinant but likely provides a basis for a versatile, adaptive recognition
      system.

PMID- 11226186
TI  - Trafficking of phosphatidylinositol 3-phosphate from the trans-Golgi network to
      the lumen of the central vacuole in plant cells.
AB  - Very limited information is available on the role of phosphatidylinositol 3
      phosphate (PI[3]P) in vesicle trafficking in plant cells. To investigate the role
      of PI(3)P during the vesicle trafficking in plant cells, we exploited the PI(3)P
      specific binding property of the endosome binding domain (EBD) (amino acids 1257
      to 1411) of human early endosome antigen 1, which is involved in endosome fusion.
      When expressed transiently in Arabidopsis protoplasts, a green fluorescent
      protein (GFP):EBD fusion protein exhibited PI(3)P-dependent localization to
      various compartments--such as the trans-Golgi network, the prevacuolar
      compartment, the tonoplasts, and the vesicles in the vacuolar lumen--that varied
      with time. The internalized GFP:EBD eventually disappeared from the lumen.
      Deletion experiments revealed that the PI(3)P-dependent localization required the
      Rab5 binding motif in addition to the zinc finger motif. Overexpression of
      GFP:EBD inhibited vacuolar trafficking of sporamin but not trafficking of H(+)
      ATPase to the plasma membrane. On the basis of these results, we propose that the
      trafficking of GFP:EBD reflects that of PI(3)P and that PI(3)P synthesized at the
      trans-Golgi network is transported to the vacuole through the prevacuolar
      compartment for degradation in plant cells.

PMID- 11226187
TI  - Wall-associated kinases are expressed throughout plant development and are
      required for cell expansion.
AB  - The mechanism by which events in the angiosperm cell wall are communicated to the
      cytoplasm is not well characterized. A family of five Arabidopsis wall-associated
      kinases (WAKs) have the potential to provide a physical and signaling continuum
      between the cell wall and the cytoplasm. The WAKs have an active cytoplasmic
      protein kinase domain, span the plasma membrane, and contain an N terminus that
      binds the cell wall. We show here that WAKs are expressed at organ junctions, in
      shoot and root apical meristems, in expanding leaves, and in response to wall
      disturbances. Leaves expressing an antisense WAK gene have reduced WAK protein
      levels and exhibit a loss of cell expansion. WAKs are covalently bound to pectin
      in the cell wall, providing evidence that the binding of a structural
      carbohydrate by a receptor-like kinase may have significance in the control of
      cell expansion.

PMID- 11226188
TI  - Transgene-induced silencing identifies sequences involved in the establishment of
      paramutation of the maize p1 gene.
AB  - A transgene carrying a distal enhancer element of the maize P1-rr promoter caused
      silencing of an endogenous P1-rr allele in the progeny of transgenic maize
      plants. Expression of both the transgene and the endogenous P1-rr allele was
      reduced in the affected plants. The silenced phenotype was observed in the
      progeny of seven of eight crosses involving three independent transgenic events
      tested (average frequency of 19%). This phenotype was associated with an induced
      epigenetic state of the P1-rr allele, termed P1-rr', which is characterized by
      increased methylation of the P1-rr flanking regions and decreased levels of P1-rr
      transcript. The P1-rr' epiallele is highly heritable in the absence of the
      inducing P1.2b::GUS transgene, and it can impose an equivalent state on a naive
      P1-rr allele in subsequent crosses (paramutation). In contrast, parallel
      experiments with two other P::GUS transgenes that contained the same basal P1-rr
      promoter fragment but different upstream sequences revealed no detectable
      silencing effect. Thus, transgenes carrying a specific enhancer fragment of the
      P1-rr gene promoter can trigger a paramutant state (P1-rr') of the endogenous P1
      rr gene that is maintained in the absence of the inducing transgene. We discuss
      the potential role of the P1-rr distal enhancer element in the establishment and
      propagation of a paramutation system in maize.

PMID- 11226189
TI  - Cell-autonomous expression of barley Mla1 confers race-specific resistance to the
      powdery mildew fungus via a Rar1-independent signaling pathway.
AB  - The barley Mla locus encodes 28 characterized resistance specificities to the
      biotrophic fungal pathogen barley powdery mildew. We describe a single-cell
      transient expression assay using entire cosmid DNAs to pinpoint Mla1 within the
      complex 240-kb Mla locus. The MLA1 cDNA encodes a 108-kD protein containing an N
      terminal coiled-coil structure, a central nucleotide binding domain, and a C
      terminal leucine-rich repeat region; it also contains a second short open reading
      frame at the 5' end that has a possible regulatory function. Although most Mla
      encoded resistance specificities require Rar1 for their function, we used the
      single-cell expression system to demonstrate that Mla1 triggers full resistance
      in the presence of the severely defective rar1-2 mutant allele. Wheat contains an
      ortholog of barley Mla, designated TaMla, that is tightly linked to (0.7
      centimorgan) but distinct from a tested resistance specificity at the complex Pm3
      locus to wheat powdery mildew. Thus, the most polymorphic powdery mildew
      resistance loci in barley and wheat may have evolved in parallel at two closely
      linked homeoloci. Barley Mla1 expressed in wheat using the single-cell
      transformation system failed to trigger a response to any of the wheat powdery
      mildew Avr genes tested, indicating that AvrMla1 is not genetically fixed in
      wheat mildew strains.

PMID- 11226190
TI  - Bus, a bushy Arabidopsis CYP79F1 knockout mutant with abolished synthesis of
      short-chain aliphatic glucosinolates.
AB  - A new mutant of Arabidopsis designated bus1-1 (for bushy), which exhibited a
      bushy phenotype with crinkled leaves and retarded vascularization, was
      characterized. The phenotype was caused by an En-1 insertion in the gene CYP79F1.
      The deduced protein belongs to the cytochrome P450 superfamily. Because members
      of the CYP79 subfamily are believed to catalyze the oxidation of amino acids to
      aldoximes, the initial step in glucosinolate biosynthesis, we analyzed the level
      of glucosinolates in a CYP79F1 null mutant (bus1-1f) and in an overexpressing
      plant. Short-chain glucosinolates derived from methionine were completely lacking
      in the null mutant and showed increased levels in the overexpressing plant,
      indicating that CYP79F1 uses short-chain methionine derivatives as substrates. In
      addition, the concentrations of indole-3-ylmethyl-glucosinolate and the content
      of the auxin indole-3-acetic acid and its precursor indole-3-acetonitrile were
      increased in the bus1-1f mutant. Our results demonstrate for the first time that
      the formation of glucosinolates derived from methionine is mediated by CYP79F1
      and that knocking out this cytochrome P450 has profound effects on plant growth
      and development.

PMID- 11226191
TI  - Import of Agrobacterium T-DNA into plant nuclei: two distinct functions of VirD2
      and VirE2 proteins.
AB  - To study the mechanism of nuclear import of T-DNA, complexes consisting of the
      virulence proteins VirD2 and VirE2 as well as single-stranded DNA (ssDNA) were
      tested for import into plant nuclei in vitro. Import of these complexes was fast
      and efficient and could be inhibited by a competitor, a nuclear localization
      signal (NLS) coupled to BSA. For import of short ssDNA, VirD2 was sufficient,
      whereas import of long ssDNA additionally required VirE2. A VirD2 mutant lacking
      its C-terminal NLS was unable to mediate import of the T-DNA complexes into
      nuclei. Although free VirE2 molecules were imported into nuclei, once bound to
      ssDNA they were not imported, implying that when complexed to DNA, the NLSs of
      VirE2 are not exposed and thus do not function. RecA, another ssDNA binding
      protein, could substitute for VirE2 in the nuclear import of T-DNA but not in
      earlier events of T-DNA transfer to plant cells. We propose that VirD2 directs
      the T-DNA complex to the nuclear pore, whereas both proteins mediate its passage
      through the pore. Therefore, by binding to ssDNA, VirE2 may shape the T-DNA
      complex such that it is accepted for translocation into the nucleus.

PMID- 11226192
TI  - Tuberization in potato involves a switch from apoplastic to symplastic phloem
      unloading.
AB  - Phloem unloading was studied in potato plants in real time during the early
      stages of tuberization using carboxyfluorescein (CF) as a phloem-mobile tracer,
      and the unloading pattern was compared with autoradiography of tubers that had
      transported (14)C assimilates. In stolons undergoing extension growth, apoplastic
      phloem unloading predominated. However, during the first visible signs of
      tuberization, a transition occurred from apoplastic to symplastic transport, and
      both CF and (14)C assimilates subsequently followed identical patterns of phloem
      unloading. It is suggested that the switch to symplastic sucrose unloading may be
      responsible for the upregulation of several genes involved in sucrose metabolism.
      A detailed analysis of sugar levels and (14)C sugar partitioning in tuberizing
      stolons revealed a distinct difference between the apical region of the tuber and
      the subapical region. Analysis of invertase activity in nontuberizing and
      tuberizing stolons revealed a marked decline in soluble invertase in the
      subapical region of swelling stolons, consistent with the switch from apoplastic
      to symplastic unloading. However, cell wall-bound invertase activity remained
      high in the apical 1 to 2 mm of tuberizing stolons. Histochemical analysis of
      potato lines transformed with the promoter of an apoplastic invertase gene
      (invGE) linked to a reporter gene also revealed discrete gene expression in the
      apical bud region. Evidence is presented that the apical and lateral tuber buds
      function as isolated domains with respect to sucrose unloading and metabolism.

PMID- 11226194
TI  - Plasma membrane-cell wall adhesion is required for expression of plant defense
      responses during fungal penetration.
AB  - Fungal pathogens almost invariably trigger cell wall-associated defense
      responses, such as extracellular hydrogen peroxide generation and callose
      deposition, when they attempt to penetrate either resistant or susceptible plant
      cells. In the current study, we provide evidence that the expression of these
      defenses is dependent on adhesion between the plant cell wall and the plasma
      membrane. Peptides containing an Arg-Gly-Asp (RGD) motif, which interfered with
      plasma membrane-cell wall adhesion as shown by the loss of the thin plasma
      membrane-cell wall connections known as Hechtian strands, reduced the expression
      of cell wall-associated defense responses during the penetration of nonhost
      plants by biotrophic fungal pathogens. This reduction was associated with
      increased fungal penetration efficiency. Neither of these effects was seen after
      treatment with similar peptides lacking the RGD motif. Disruption of plant
      microfilaments had no effect on Hechtian strands but mimicked the effect of RGD
      peptides on wall defenses, suggesting that the expression of cell wall-associated
      defenses involves communication between the plant cell wall and the cytosol
      across the plasma membrane. To visualize the state of the plasma membrane-cell
      wall interaction during fungal penetration, we observed living cells during
      sucrose-induced plasmolysis. In interactions that were characterized by the early
      expression of cell wall-associated defenses, there was no change, or an increase,
      in plasma membrane-cell wall adhesion under the penetration point as the fungus
      grew through the plant cell wall. In contrast, for rust fungus interactions with
      host plants, there was a strong correlation between a lack of cell wall
      associated defenses and a localized decrease in plasma membrane-cell wall
      adhesion under the penetration point. Abolition of this localized decreased
      adhesion by previous inoculation with a fungus that increased plasma membrane
      cell wall adhesion resulted in reduced penetration by the rust fungus and
      induction of cell wall-associated defenses. These results suggest that rust fungi
      may induce a decrease in plasma membrane-cell wall adhesion as a means of
      disrupting the expression of nonspecific defense responses during penetration of
      host cells.

PMID- 11226193
TI  - Cip4, a new COP1 target, is a nucleus-localized positive regulator of Arabidopsis
      photomorphogenesis.
AB  - Arabidopsis COP1 acts within the nucleus to repress photomorphogenesis, and its
      nuclear abundance is negatively regulated by light. Here, we report the
      identification of a COP1-interactive partner, CIP4. CIP4 is a nuclear protein and
      a potent transcription coactivator. Conditional suppression of CIP4 expression
      resulted in an elongated hypocotyl and reduced chlorophyll content in the light,
      indicating that CIP4 is required for the promotion of photomorphogenesis.
      Furthermore, CIP4 was revealed to act downstream of multiple photoreceptors as
      well as COP1 in mediating light control of development. CIP4 expression is light
      inducible and regulated by COP1. However, CIP4 does not play a role in mediating
      the light induction of anthocyanin accumulation. Together with our previous
      studies of CIP7 and HY5, our data suggest that COP1 interacts directly with and
      regulates multiple physiological targets, which in turn regulate distinct sets of
      light-regulated responses.

PMID- 11226195
TI  - The Arabidopsis HY2 gene encodes phytochromobilin synthase, a ferredoxin
      dependent biliverdin reductase.
AB  - Light perception by the plant photoreceptor phytochrome requires the tetrapyrrole
      chromophore phytochromobilin (P Phi B), which is covalently attached to a large
      apoprotein. Arabidopsis mutants hy1 and hy2, which are defective in P Phi B
      biosynthesis, display altered responses to light due to a deficiency in
      photoactive phytochrome. Here, we describe the isolation of the HY2 gene by map
      based cloning. hy2 mutant alleles possess alterations within this locus, some of
      which affect the expression of the HY2 transcript. HY2 encodes a soluble protein
      precursor of 38 kD with a putative N-terminal plastid transit peptide. The HY2
      transit peptide is sufficient to localize the reporter green fluorescent protein
      to plastids. Purified mature recombinant HY2 protein exhibits P Phi B synthase
      activity (i.e., ferredoxin-dependent reduction of biliverdin IX alpha to P Phi
      B), as confirmed by HPLC and by the ability of the bilin reaction products to
      combine with apophytochrome to yield photoactive holophytochrome. Database
      searches and hybridization studies suggest that HY2 is a unique gene in the
      Arabidopsis genome that is related to a family of proteins found in oxygenic
      photosynthetic bacteria.

PMID- 11226197
TI  - Scaling of growth: plants and animals are not so different.

PMID- 11226196
TI  - Arabidopsis NHO1 is required for general resistance against Pseudomonas bacteria.
AB  - Nonhost interactions are prevalent between plants and specialized phytopathogens.
      Although it has great potential for providing crop plants with durable
      resistance, nonhost resistance is poorly understood. Here, we show that nonhost
      resistance is controlled, at least in part, by general resistance. Arabidopsis
      plants are resistant to the nonhost pathogen Pseudomonas syringae pv phaseolicola
      NPS3121 and completely arrest bacterial multiplication in the plant. Ten
      Arabidopsis mutants were isolated that were compromised in nonhost (nho)
      resistance to P. s. phaseolicola. Among these, nho1 is caused by a single
      recessive mutation that defines a novel gene. nho1 is defective in nonspecific
      resistance to Pseudomonas bacteria, because it also supported the growth of P. s.
      tabaci and P. fluorescens bacteria, both of which are nonpathogenic on
      Arabidopsis. In addition, the nho1 mutation also compromised resistance mediated
      by RPS2, RPS4, RPS5, and RPM1. Interestingly, the nho1 mutation had no effect on
      the growth of the virulent bacteria P. s. maculicola ES4326 and P. s. tomato
      DC3000, but it partially restored the in planta growth of the DC3000 hrpS(-)
      mutant bacteria. Thus, the virulent bacteria appear to evade or suppress NHO1
      mediated resistance by means of an Hrp-dependent virulence mechanism.

PMID- 11226198
TI  - H1N1-influenza as Lazarus: genomic resurrection from the tomb of an unknown.

PMID- 11226199
TI  - The disintegration of a molecule: the role of gelsolin in FAF, familial
      amyloidosis (Finnish type).

PMID- 11226200
TI  - Was "molecular opportunism" a factor in the evolution of different photosynthetic
      light-harvesting pigment systems?

PMID- 11226201
TI  - PEDF: Raising both hopes and questions in controlling angiogenesis.

PMID- 11226202
TI  - Making sense out of nonsense.

PMID- 11226203
TI  - Planetary exploration in the time of astrobiology: protecting against biological
      contamination.
AB  - These are intriguing times in the exploration of other solar-system bodies.
      Continuing discoveries about life on Earth and the return of data suggesting the
      presence of liquid water environments on or under the surfaces of other planets
      and moons have combined to suggest the significant possibility that
      extraterrestrial life may exist in this solar system. Similarly, not since the
      Viking missions of the mid-1970s has there been as great an appreciation for the
      potential for Earth life to contaminate other worlds. Current plans for the
      exploration of the solar system include constraints intended to prevent
      biological contamination from being spread by solar-system exploration missions.

PMID- 11226204
TI  - Use of spacecraft data to derive regions on Mars where liquid water would be
      stable.
AB  - Combining Viking pressure and temperature data with Mars Orbital Laser Altimeter
      topography data, we have computed the fraction of the martian year during which
      pressure and temperature allow for liquid water to be stable on the martian
      surface. We find that liquid water would be stable within the Hellas and Argyre
      basin and over the northern lowlands equatorward of about 40 degrees. The
      location with the maximum period of stable conditions for liquid water is in the
      southeastern portion of Utopia Planitia, where 34% of the year liquid water would
      be stable if it were present. Locations of stability appear to correlate with the
      distribution of valley networks.

PMID- 11226205
TI  - Extraterrestrial amino acids in Orgueil and Ivuna: tracing the parent body of CI
      type carbonaceous chondrites.
AB  - Amino acid analyses using HPLC of pristine interior pieces of the CI carbonaceous
      chondrites Orgueil and Ivuna have found that beta-alanine, glycine, and gamma
      amino-n-butyric acid (ABA) are the most abundant amino acids in these two
      meteorites, with concentrations ranging from approximately 600 to 2,000 parts per
      billion (ppb). Other alpha-amino acids such as alanine, alpha-ABA, alpha
      aminoisobutyric acid (AIB), and isovaline are present only in trace amounts (<200
      ppb). Carbon isotopic measurements of beta-alanine and glycine and the presence
      of racemic (D/L approximately 1) alanine and beta-ABA in Orgueil suggest that
      these amino acids are extraterrestrial in origin. In comparison to the CM
      carbonaceous chondrites Murchison and Murray, the amino acid composition of the
      CIs is strikingly distinct, suggesting that these meteorites came from a
      different type of parent body, possibly an extinct comet, than did the CM
      carbonaceous chondrites.

PMID- 11226206
TI  - Organic protomolecule assembly in igneous minerals.
AB  - CH stretching bands, nu(CH), in the infrared spectrum of single crystals of
      nominally high purity, of laboratory-grown MgO, and of natural upper mantle
      olivine, provide an "organic" signature that closely resembles the symmetrical
      and asymmetrical C--H stretching modes of aliphatic -CH(2) units. The nu(CH)
      bands indicate that H(2)O and CO(2), dissolved in the matrix of these minerals,
      converted to form H(2) and chemically reduced C, which in turn formed C--H
      entities, probably through segregation into defects such as dislocations. Heating
      causes the C--H bonds to pyrolyze and the nu(CH) bands to disappear, but
      annealing at 70 degrees C causes them to reappear within a few days or weeks.
      Modeling dislocations in MgO suggests that the segregation of C can lead to C(x)
      chains, x = 4, with the terminal C atoms anchored to the MgO matrix by bonding to
      two O(-). Allowing H(2) to react with such C(x) chains leads to
      [O(2)C(CH(2))(2)CO(2)] or similar precipitates. It is suggested that such C(x)-
      H(y)--O(z) entities represent protomolecules from which derive the short-chain
      carboxylic and dicarboxylic and the medium-chain fatty acids that have been
      solvent-extracted from crushed MgO and olivine single crystals, respectively.
      Thus, it appears that the hard, dense matrix of igneous minerals represents a
      medium in which protomolecular units can be assembled. During weathering of
      rocks, the protomolecular units turn into complex organic molecules. These
      processes may have provided stereochemically constrained organics to the early
      Earth that were crucial to the emergence of life.

PMID- 11226207
TI  - Oxygen isotope ratios of PO4: an inorganic indicator of enzymatic activity and P
      metabolism and a new biomarker in the search for life.
AB  - The distinctive relations between biological activity and isotopic effect
      recorded in biomarkers (e.g., carbon and sulfur isotope ratios) have allowed
      scientists to suggest that life originated on this planet nearly 3.8 billion
      years ago. The existence of life on other planets may be similarly identified by
      geochemical biomarkers, including the oxygen isotope ratio of phosphate
      (delta(18)O(p)) presented here. At low near-surface temperatures, the exchange of
      oxygen isotopes between phosphate and water requires enzymatic catalysis. Because
      enzymes are indicative of cellular activity, the demonstration of enzyme
      catalyzed PO(4)-H(2)O exchange is indicative of the presence of life. Results of
      laboratory experiments are presented that clearly show that delta(18)O(P) values
      of inorganic phosphate can be used to detect enzymatic activity and microbial
      metabolism of phosphate. Applications of delta(18)O(p) as a biomarker are
      presented for two Earth environments relevant to the search for extraterrestrial
      life: a shallow groundwater reservoir and a marine hydrothermal vent system. With
      the development of in situ analytical techniques and future planned sample return
      strategies, delta(18)O(p) may provide an important biosignature of the presence
      of life in extraterrestrial systems such as that on Mars.

PMID- 11226208
TI  - Keeping Mars warm with new super greenhouse gases.
AB  - Our selection of new super greenhouse gases to fill a putative "window" in a
      future Martian atmosphere relies on quantum-mechanical calculations. Our study
      indicates that if Mars could somehow acquire an Earth-like atmospheric
      composition and surface pressure, then an Earth-like temperature could be
      sustained by a mixture of five to seven fluorine compounds. Martian mining
      requirements for replenishing the fluorine could be comparable to current
      terrestrial extraction.

PMID- 11226209
TI  - A novel microbial habitat in the mid-ocean ridge subseafloor.
AB  - The subseafloor at the mid-ocean ridge is predicted to be an excellent microbial
      habitat, because there is abundant space, fluid flow, and geochemical energy in
      the porous, hydrothermally influenced oceanic crust. These characteristics also
      make it a good analog for potential subsurface extraterrestrial habitats.
      Subseafloor environments created by the mixing of hot hydrothermal fluids and
      seawater are predicted to be particularly energy-rich, and hyperthermophilic
      microorganisms that broadly reflect such predictions are ejected from these
      systems in low-temperature ( approximately 15 degrees C), basalt-hosted diffuse
      effluents. Seven hyperthermophilic heterotrophs isolated from low-temperature
      diffuse fluids exiting the basaltic crust in and near two hydrothermal vent
      fields on the Endeavour Segment, Juan de Fuca Ridge, were compared
      phylogenetically and physiologically to six similarly enriched hyperthermophiles
      from samples associated with seafloor metal sulfide structures. The 13 organisms
      fell into four distinct groups: one group of two organisms corresponding to the
      genus Pyrococcus and three groups corresponding to the genus Thermococcus. Of
      these three groups, one was composed solely of sulfide-derived organisms, and the
      other two related groups were composed of subseafloor organisms. There was no
      evidence of restricted exchange of organisms between sulfide and subseafloor
      habitats, and therefore this phylogenetic distinction indicates a selective force
      operating between the two habitats. Hypotheses regarding the habitat differences
      were generated through comparison of the physiology of the two groups of
      hyperthermophiles; some potential differences between these habitats include
      fluid flow stability, metal ion concentrations, and sources of complex organic
      matter.

PMID- 11226210
TI  - Truncated hexa-octahedral magnetite crystals in ALH84001: presumptive
      biosignatures.
AB  - McKay et al. [(1996) Science 273, 924-930] suggested that carbonate globules in
      the meteorite ALH84001 contained the fossil remains of Martian microbes. We have
      characterized a subpopulation of magnetite (Fe(3)O(4)) crystals present in
      abundance within the Fe-rich rims of these carbonate globules. We find these
      Martian magnetites to be both chemically and physically identical to terrestrial,
      biogenically precipitated, intracellular magnetites produced by magnetotactic
      bacteria strain MV-1. Specifically, both magnetite populations are single-domain
      and chemically pure, and exhibit a unique crystal habit we describe as truncated
      hexa-octahedral. There are no known reports of inorganic processes to explain the
      observation of truncated hexa-octahedral magnetites in a terrestrial sample. In
      bacteria strain MV-1 their presence is therefore likely a product of Natural
      Selection. Unless there is an unknown and unexplained inorganic process on Mars
      that is conspicuously absent on the Earth and forms truncated hexa-octahedral
      magnetites, we suggest that these magnetite crystals in the Martian meteorite
      ALH84001 were likely produced by a biogenic process. As such, these crystals are
      interpreted as Martian magnetofossils and constitute evidence of the oldest life
      yet found.

PMID- 11226212
TI  - Chains of magnetite crystals in the meteorite ALH84001: evidence of biological
      origin.
AB  - The presence of magnetite crystal chains, considered missing evidence for the
      biological origin of magnetite in ALH84001 [Thomas-Keprta, K. L., Bazylinski, D.
      A., Kirschvink, J. L., Clemett, S. J., McKay, D. S., Wentworth, S. J., Vali, H.,
      Gibson, E. K., Jr., & Romanek, C. S. (2000) Geochim. Cosmochim. Acta 64, 4049
      4081], is demonstrated by high-power stereo backscattered scanning electron
      microscopy. Five characteristics of such chains (uniform crystal size and shape
      within chains, gaps between crystals, orientation of elongated crystals along the
      chain axis, flexibility of chains, and a halo that is a possible remnant of a
      membrane around chains), observed or inferred to be present in magnetotactic
      bacteria but incompatible with a nonbiological origin, are shown to be present.
      Although it is unlikely that magnetotactic bacteria were ever alive in ALH84001,
      decomposed remains of such organisms could have been deposited in cracks in the
      rock while it was still on the surface on Mars.

PMID- 11226211
TI  - The origin of atmospheric oxygen on Earth: the innovation of oxygenic
      photosynthesis.
AB  - The evolution of O(2)-producing cyanobacteria that use water as terminal
      reductant transformed Earth's atmosphere to one suitable for the evolution of
      aerobic metabolism and complex life. The innovation of water oxidation freed
      photosynthesis to invade new environments and visibly changed the face of the
      Earth. We offer a new hypothesis for how this process evolved, which identifies
      two critical roles for carbon dioxide in the Archean period. First, we present a
      thermodynamic analysis showing that bicarbonate (formed by dissolution of CO(2))
      is a more efficient alternative substrate than water for O(2) production by
      oxygenic phototrophs. This analysis clarifies the origin of the long debated
      "bicarbonate effect" on photosynthetic O(2) production. We propose that
      bicarbonate was the thermodynamically preferred reductant before water in the
      evolution of oxygenic photosynthesis. Second, we have examined the speciation of
      manganese(II) and bicarbonate in water, and find that they form Mn-bicarbonate
      clusters as the major species under conditions that model the chemistry of the
      Archean sea. These clusters have been found to be highly efficient precursors for
      the assembly of the tetramanganese-oxide core of the water-oxidizing enzyme
      during biogenesis. We show that these clusters can be oxidized at electrochemical
      potentials that are accessible to anoxygenic phototrophs and thus the most likely
      building blocks for assembly of the first O(2) evolving photoreaction center,
      most likely originating from green nonsulfur bacteria before the evolution of
      cyanobacteria.

PMID- 11226213
TI  - Constraints on nebular dynamics and chemistry based on observations of annealed
      magnesium silicate grains in comets and in disks surrounding Herbig Ae/Be stars.
AB  - Understanding dynamic conditions in the Solar Nebula is the key to prediction of
      the material to be found in comets. We suggest that a dynamic, large-scale
      circulation pattern brings processed dust and gas from the inner nebula back out
      into the region of cometesimal formation-extending possibly hundreds of
      astronomical units (AU) from the sun-and that the composition of comets is
      determined by a chemical reaction network closely coupled to the dynamic
      transport of dust and gas in the system. This scenario is supported by laboratory
      studies of Mg silicates and the astronomical data for comets and for
      protoplanetary disks associated with young stars, which demonstrate that
      annealing of nebular silicates must occur in conjunction with a large-scale
      circulation. Mass recycling of dust should have a significant effect on the
      chemical kinetics of the outer nebula by introducing reduced, gas-phase species
      produced in the higher temperature and pressure environment of the inner nebula,
      along with freshly processed grains with "clean" catalytic surfaces to the region
      of cometesimal formation. Because comets probably form throughout the lifetime of
      the Solar Nebula and processed (crystalline) grains are not immediately available
      for incorporation into the first generation of comets, an increasing fraction of
      dust incorporated into a growing comet should be crystalline olivine and this
      fraction can serve as a crude chronometer of the relative ages of comets. The
      formation and evolution of key organic and biogenic molecules in comets are
      potentially of great consequence to astrobiology.

PMID- 11226214
TI  - Solvent effects on the energy landscapes and folding kinetics of polyalanine.
AB  - The effect of a solvation on the thermodynamics and kinetics of polyalanine
      (Ala(12)) is explored on the basis of its energy landscapes in vacuum and in an
      aqueous solution. Both energy landscapes are characterized by two basins, one
      associated with alpha-helical structures and the other with coil and beta
      structures of the peptide. In both environments, the basin that corresponds to
      the alpha-helical structure is considerably narrower than the basin corresponding
      to the beta-state, reflecting their different contributions to the entropy of the
      peptide. In vacuum, the alpha-helical state of Ala(12) constitutes the native
      state, in agreement with common helical propensity scales, whereas in the aqueous
      medium, the alpha-helical state is destabilized, and the beta-state becomes the
      native state. Thus solvation has a dramatic effect on the energy landscape of
      this peptide, resulting in an inverted stability of the two states. Different
      folding and unfolding time scales for Ala(12) in hydrophilic and hydrophobic
      chemical environments are caused by the higher entropy of the native state in
      water relative to vacuum. The concept of a helical propensity has to be extended
      to incorporate environmental solvent effects.

PMID- 11226215
TI  - On the acidity and reactivity of HNO in aqueous solution and biological systems.
AB  - The gas phase and aqueous thermochemistry and reactivity of nitroxyl (nitrosyl
      hydride, HNO) were elucidated with multiconfigurational self-consistent field and
      hybrid density functional theory calculations and continuum solvation methods.
      The pK(a) of HNO is predicted to be 7.2 +/- 1.0, considerably different from the
      value of 4.7 reported from pulse radiolysis experiments. The ground-state triplet
      nature of NO(-) affects the rates of acid-base chemistry of the HNO/NO(-) couple.
      HNO is highly reactive toward dimerization and addition of soft nucleophiles but
      is predicted to undergo negligible hydration (K(eq) = 6.9 x 10(-5)). HNO is
      predicted to exist as a discrete species in solution and is a viable participant
      in the chemical biology of nitric oxide and derivatives.

PMID- 11226217
TI  - Active site mutant transgene confers tolerance to human beta-glucuronidase
      without affecting the phenotype of MPS VII mice.
AB  - Mucopolysaccharidosis type VII (MPS VII; Sly syndrome) is an autosomal recessive
      lysosomal storage disorder due to an inherited deficiency of beta-glucuronidase.
      A naturally occurring mouse model for this disease was discovered at The Jackson
      Laboratory and shown to be due to homozygosity for a 1-bp deletion in exon 10 of
      the gus gene. The murine model MPS VII (gus(mps/mps)) has been very well
      characterized and used extensively to evaluate experimental strategies for
      lysosomal storage diseases, including bone marrow transplantation, enzyme
      replacement therapy, and gene therapy. To enhance the value of this model for
      enzyme and gene therapy, we produced a transgenic mouse expressing the human beta
      glucuronidase cDNA with an amino acid substitution at the active site nucleophile
      (E540A) and bred it onto the MPS VII (gus(mps/mps)) background. We demonstrate
      here that the mutant mice bearing the active site mutant human transgene retain
      the clinical, morphological, biochemical, and histopathological characteristics
      of the original MPS VII (gus(mps/mps)) mouse. However, they are now tolerant to
      immune challenge with human beta-glucuronidase. This "tolerant MPS VII mouse
      model" should be useful for preclinical trials evaluating the effectiveness of
      enzyme and/or gene therapy with the human gene products likely to be administered
      to human patients with MPS VII.

PMID- 11226216
TI  - Delineating developmental and metabolic pathways in vivo by expression profiling
      using the RIKEN set of 18,816 full-length enriched mouse cDNA arrays.
AB  - We have systematically characterized gene expression patterns in 49 adult and
      embryonic mouse tissues by using cDNA microarrays with 18,816 mouse cDNAs.
      Cluster analysis defined sets of genes that were expressed ubiquitously or in
      similar groups of tissues such as digestive organs and muscle. Clustering of
      expression profiles was observed in embryonic brain, postnatal cerebellum, and
      adult olfactory bulb, reflecting similarities in neurogenesis and remodeling.
      Finally, clustering genes coding for known enzymes into 78 metabolic pathways
      revealed a surprising coordination of expression within each pathway among
      different tissues. On the other hand, a more detailed examination of glycolysis
      revealed tissue-specific differences in profiles of key regulatory enzymes. Thus,
      by surveying global gene expression by using microarrays with a large number of
      elements, we provide insights into the commonality and diversity of pathways
      responsible for the development and maintenance of the mammalian body plan.

PMID- 11226219
TI  - Nanohedra: using symmetry to design self assembling protein cages, layers,
      crystals, and filaments.
AB  - A general strategy is described for designing proteins that self assemble into
      large symmetrical nanomaterials, including molecular cages, filaments, layers,
      and porous materials. In this strategy, one molecule of protein A, which
      naturally forms a self-assembling oligomer, A(n), is fused rigidly to one
      molecule of protein B, which forms another self-assembling oligomer, B(m). The
      result is a fusion protein, A-B, which self assembles with other identical copies
      of itself into a designed nanohedral particle or material, (A-B)(p). The strategy
      is demonstrated through the design, production, and characterization of two
      fusion proteins: a 49-kDa protein designed to assemble into a cage approximately
      15 nm across, and a 44-kDa protein designed to assemble into long filaments
      approximately 4 nm wide. The strategy opens a way to create a wide variety of
      potentially useful protein-based materials, some of which share similar features
      with natural biological assemblies.

PMID- 11226218
TI  - pRB induces Sp1 activity by relieving inhibition mediated by MDM2.
AB  - pRB activates transcription by a poorly understood mechanism that involves
      relieving negative regulation of the promoter specificity factor Sp1. We show
      here that MDM2 inhibits Sp1-mediated transcription, that MDM2 binds directly to
      Sp1 in vitro as well as in vivo, and that MDM2 inhibits the DNA-binding activity
      of Sp1. Forced expression of pRB relieves MDM2-mediated repression, and
      interaction of pRB with the MDM2-Sp1 complex releases Sp1 and restores DNA
      binding. These results suggest a model in which the opposing activities of MDM2
      and pRB regulate Sp1 DNA-binding and transcriptional activity.

PMID- 11226220
TI  - Mutated plant lectin library useful to identify different cells.
AB  - The 24 nucleotides comprising the carbohydrate-recognition domain of Maackia
      amurensis hemagglutinin (MAH) cDNA were randomly mutated. The mutant lectins were
      expressed as glutathione-S-transferase fusion proteins in Escherichia coli and 16
      clones were randomly chosen. Although all of 16 recombinant lectins reacted
      strongly with anti-MAH polyclonal antibody, the carbohydrate-recognition domain
      of each was unique. As shown by agglutination studies, each mutant MAH lectin was
      able to bind to erythrocytes from one or more of five animal species in very
      distinct patterns. Thus, novel plant lectin libraries can be used to discriminate
      in a highly specific manner among a variety of cell types. This technology may
      prove to be very useful in a number of different applications requiring a high
      level of specificity in cell identification.

PMID- 11226221
TI  - Distinct roles for the N- and C-terminal regions in the cytotoxicity of pierisin
      1, a putative ADP-ribosylating toxin from cabbage butterfly, against mammalian
      cells.
AB  - Pierisin-1 is an 850-aa cytotoxic protein found in the cabbage butterfly, Pieris
      rapae, and has been suggested to consist of an N-terminal region with ADP
      ribosyltransferase domain and of a C-terminal region that might have a receptor
      binding domain. To elucidate the role of each region, we investigated the
      functions of various fragments of pierisin-1. In vitro expressed polypeptide
      consisting of amino acid residues 1-233 or 234-850 of pierisin-1 alone did not
      show cytotoxicity against human cervical carcinoma HeLa cells. However, the
      presence of both polypeptides in the culture medium showed some of the original
      cytotoxic activity. Introduction of the N-terminal polypeptide alone by
      electroporation also induced cell death in HeLa cells, and even in the mouse
      melanoma MEB4 cells insensitive to pierisin-1. Thus, the N-terminal region has a
      principal role in the cytotoxicity of pierisin-1 inside mammalian cells. Analyses
      of incorporated pierisin-1 indicated that the entire protein, regardless of
      whether it consisted of a single polypeptide or two separate N- and C-terminal
      polypeptides, was incorporated into HeLa cells. However, neither of the terminal
      polypeptides was incorporated when each polypeptide was present separately. These
      findings indicate that the C-terminal region is important for the incorporation
      of pierisin-1. Moreover, presence of receptor for pierisin-1 in the lipid
      fraction of cell membrane was suggested. The cytotoxic effects of pierisin-1 were
      enhanced by previous treatment with trypsin, producing "nicked" pierisin-1.
      Generation of the N-terminal fragment in HeLa cells was detected after
      application of intact entire molecule of pierisin-1. From the above observations,
      it is suggested that after incorporation of pierisin-1 into the cell by
      interaction of its C-terminal region with the receptor in the cell membrane, the
      entire protein is cleaved into the N- and C-terminal fragments with intracellular
      protease, and the N-terminal fragment then exhibits cytotoxicity.

PMID- 11226222
TI  - The nitrite reductase from Pseudomonas aeruginosa: essential role of two active
      site histidines in the catalytic and structural properties.
AB  - Cd(1) nitrite reductase catalyzes the conversion of nitrite to NO in denitrifying
      bacteria. Reduction of the substrate occurs at the d(1)-heme site, which faces on
      the distal side some residues thought to be essential for substrate binding and
      catalysis. We report the results obtained by mutating to Ala the two invariant
      active site histidines, His-327 and His-369, of the enzyme from Pseudomonas
      aeruginosa. Both mutants have lost nitrite reductase activity but maintain the
      ability to reduce O(2) to water. Nitrite reductase activity is impaired because
      of the accumulation of a catalytically inactive form, possibly because the
      productive displacement of NO from the ferric d(1)-heme iron is impaired.
      Moreover, the two distal His play different roles in catalysis; His-369 is
      absolutely essential for the stability of the Michaelis complex. The structures
      of both mutants show (i) the new side chain in the active site, (ii) a loss of
      density of Tyr-10, which slipped away with the N-terminal arm, and (iii) a large
      topological change in the whole c-heme domain, which is displaced 20 A from the
      position occupied in the wild-type enzyme. We conclude that the two invariant His
      play a crucial role in the activity and the structural organization of cd(1)
      nitrite reductase from P. aeruginosa.

PMID- 11226223
TI  - A short segment within the cytoplasmic domain of the neural cell adhesion
      molecule (N-CAM) is essential for N-CAM-induced NF-kappa B activity in
      astrocytes.
AB  - The neural cell adhesion molecule (N-CAM) is expressed on the surface of
      astrocytes, where its homophilic binding leads to the activation of the
      transcription factor NF-kappaB. Transfection of astrocytes with a construct
      encompassing the transmembrane region and the cytoplasmic domain of N-CAM
      (designated Tm-Cyto, amino acids 685-839 in the full-length molecule) inhibited
      this activation up to 40%, and inhibited N-CAM-induced translocation of NF-kappaB
      to the nucleus. N-CAM also activated NF-kappaB in astrocytes from N-CAM knockout
      mice, presumably through binding to a heterophile. This activation, however, was
      not blocked by Tm-Cyto expression, indicating that the inhibitory effect of the
      Tm-Cyto construct is specific for cell surface N-CAM. Deletions and point
      mutations of the cytoplasmic portion of the Tm-Cyto construct indicated that the
      region between amino acids 780 and 800 were essential for inhibitory activity.
      This region contains four threonines (788, 793, 794, and 797). Mutation to
      alanine of T788, T794, or T797, but not T793, abolished inhibitory activity, as
      did mutation of T788 or T797 to aspartic acid. A Tm-Cyto construct with T794
      mutated to aspartic acid retained inhibitory activity but did not itself induce a
      constitutive NF-kappaB response. This result suggests that phosphorylation of
      T794 may be necessary but is not the triggering event. Overall, these findings
      define a short segment of the N-CAM cytoplasmic domain that is critical for N-CAM
      induced activation of NF-kappaB and may be important in other N-CAM-mediated
      signaling.

PMID- 11226224
TI  - Supernatant protein factor, which stimulates the conversion of squalene to
      lanosterol, is a cytosolic squalene transfer protein and enhances cholesterol
      biosynthesis.
AB  - Squalene epoxidase, a membrane-associated enzyme that converts squalene to
      squalene 2,3-oxide, plays an important role in the maintenance of cholesterol
      homeostasis. In 1957, Bloch and colleagues identified a factor from rat liver
      cytosol termed "supernatant protein factor (SPF)," which promotes the squalene
      epoxidation catalyzed by rat liver microsomes with oxygen, NADPH, FAD, and
      phospholipid [Tchen, T. T. & Bloch, K. (1957) J. Biol. Chem. 226, 921-930].
      Although purification of SPF by 11,000-fold was reported, no information is so
      far available on the primary structure or biological function of SPF. Here we
      report the cDNA cloning and expression of SPF from rat and human. The encoded
      protein of 403 amino acids belongs to a family of cytosolic lipid
      binding/transfer proteins such as alpha-tocopherol transfer protein, cellular
      retinal binding protein, yeast phosphatidylinositol transfer protein (Sec14p),
      and squid retinal binding protein. Recombinant SPF produced in Escherichia coli
      enhances microsomal squalene epoxidase activity and promotes intermembrane
      transfer of squalene in vitro. SPF mRNA is expressed abundantly in the liver and
      small intestine, both of which are important sites of cholesterol biosynthesis.
      SPF is expressed significantly in isolated hepatocytes, but the expression level
      was markedly decreased after 48 h of in vitro culture. Moreover, SPF was not
      detectable in most of the cell lines tested, including HepG2 and McARH7777
      hepatomas. Transfection of SPF cDNA in McARH7777 significantly stimulated de novo
      cholesterol biosynthesis. These data suggest that SPF is a cytosolic squalene
      transfer protein capable of regulating cholesterol biosynthesis.

PMID- 11226225
TI  - Polar residues drive association of polyleucine transmembrane helices.
AB  - Although many polar residues are directly involved in transmembrane protein
      functions, the extent to which they contribute to more general structural
      features is still unclear. Previous studies have demonstrated that asparagine
      residues can drive transmembrane helix association through interhelical hydrogen
      bonding [Choma, C., Gratkowski, H., Lear, J. D. & DeGrado, W. F. (2000) Nat.
      Struct. Biol. 7, 161-166; and Zhou, F. X., Cocco, M. J., Russ, W. P., Brunger, A.
      T. & Engelman, D. M. (2000) Nat. Struct. Biol. 7, 154-160]. We have studied the
      ability of other polar residues to promote helix association in detergent
      micelles and in biological membranes. Our results show that polyleucine sequences
      with Asn, Asp, Gln, Glu, and His, residues capable of being simultaneously
      hydrogen bond donors and acceptors, form homo- or heterooligomers. In contrast,
      polyleucine sequences with Ser, Thr, and Tyr do not associate more than the
      polyleucine sequence alone. The results therefore provide experimental evidence
      that interactions between polar residues in the helices of transmembrane proteins
      may serve to provide structural stability and oligomerization specificity.
      Furthermore, such interactions can allow structural flexibility required for the
      function of some membrane proteins.

PMID- 11226226
TI  - Identification in mice of two isoforms of the cysteinyl leukotriene 1 receptor
      that result from alternative splicing.
AB  - Two classes of human G protein-coupled receptors, cysteinyl leukotriene 1
      (CysLT(1)) and CysLT(2) receptors, recently have been characterized and cloned.
      Because the CysLT(1) receptor blockers are effective in treating human bronchial
      asthma and the mouse is often used to model human diseases, we isolated the mouse
      CysLT(1) receptor from a mouse lung cDNA library and found two isoforms. A short
      isoform cDNA containing two exons encodes a polypeptide of 339 aa with 87.3%
      amino acid identity to the human CysLT(1) receptor. A long isoform has two
      additional exons and an in-frame upstream start codon resulting in a 13-aa
      extension at the N terminus. Northern blot analysis revealed that the mouse
      CysLT(1) receptor mRNA is expressed in lung and skin; and reverse transcription
      PCR showed wide expression of the long isoform with the strongest presence in
      lung and skin. The gene for the mouse CysLT(1) receptor was mapped to band XD.
      Leukotriene (LT) D(4) induced intracellular calcium mobilization in Chinese
      hamster ovary cells stably expressing either isoform of the mouse CysLT(1)
      receptor cDNA. This agonist effect of LTD(4) was fully inhibited by the CysLT(1)
      receptor antagonist, MK-571. Microsomal membranes from each transformant showed a
      single class of binding sites for [(3)H]LTD(4); and the binding was blocked by
      unlabeled LTs, with the rank order of affinities being LTD(4) >> LTE(4) = LTC(4)
      >> LTB(4). Thus, the dominant mouse isoform with the N-terminal amino acid
      extension encoded by an additional exon has the same ligand response profile as
      the spliced form and the human receptor.

PMID- 11226227
TI  - Arabidopsis cyt1 mutants are deficient in a mannose-1-phosphate
      guanylyltransferase and point to a requirement of N-linked glycosylation for
      cellulose biosynthesis.
AB  - Arabidopsis cyt1 mutants have a complex phenotype indicative of a severe defect
      in cell wall biogenesis. Mutant embryos arrest as wide, heart-shaped structures
      characterized by ectopic accumulation of callose and the occurrence of incomplete
      cell walls. Texture and thickness of the cell walls are irregular, and
      unesterified pectins show an abnormally diffuse distribution. To determine the
      molecular basis of these defects, we have cloned the CYT1 gene by a map-based
      approach and found that it encodes mannose-1-phosphate guanylyltransferase. A
      weak mutation in the same gene, called vtc1, has previously been identified on
      the basis of ozone sensitivity due to reduced levels of ascorbic acid. Mutant
      cyt1 embryos are deficient in N-glycosylation and have an altered composition of
      cell wall polysaccharides. Most notably, they show a 5-fold decrease in cellulose
      content. Characteristic aspects of the cyt1 phenotype, including radial swelling
      and accumulation of callose, can be mimicked with the inhibitor of N
      glycosylation, tunicamycin. Our results suggest that N-glycosylation is required
      for cellulose biosynthesis and that a deficiency in this process can account for
      most phenotypic features of cyt1 embryos.

PMID- 11226228
TI  - Twenty-first aminoacyl-tRNA synthetase-suppressor tRNA pairs for possible use in
      site-specific incorporation of amino acid analogues into proteins in eukaryotes
      and in eubacteria.
AB  - Two critical requirements for developing methods for the site-specific
      incorporation of amino acid analogues into proteins in vivo are (i) a suppressor
      tRNA that is not aminoacylated by any of the endogenous aminoacyl-tRNA
      synthetases (aaRSs) and (ii) an aminoacyl-tRNA synthetase that aminoacylates the
      suppressor tRNA but no other tRNA in the cell. Here we describe two such aaRS
      suppressor tRNA pairs, one for use in the yeast Saccharomyces cerevisiae and
      another for use in Escherichia coli. The "21st synthetase-tRNA pairs" include E.
      coli glutaminyl-tRNA synthetase (GlnRS) along with an amber suppressor derived
      from human initiator tRNA, for use in yeast, and mutants of the yeast tyrosyl
      tRNA synthetase (TyrRS) along with an amber suppressor derived from E. coli
      initiator tRNA, for use in E. coli. The suppressor tRNAs are aminoacylated in
      vivo only in the presence of the heterologous aaRSs, and the aminoacylated tRNAs
      function efficiently in suppression of amber codons. Plasmids carrying the E.
      coli GlnRS gene can be stably maintained in yeast. However, plasmids carrying the
      yeast TyrRS gene could not be stably maintained in E. coli. This lack of
      stability is most likely due to the fact that the wild-type yeast TyrRS
      misaminoacylates the E. coli proline tRNA. By using error-prone PCR, we have
      isolated and characterized three mutants of yeast TyrRS, which can be stably
      expressed in E. coli. These mutants still aminoacylate the suppressor tRNA
      essentially quantitatively in vivo but show increased discrimination in vitro for
      the suppressor tRNA over the E. coli proline tRNA by factors of 2.2- to 6.8-fold.

PMID- 11226229
TI  - Viral capsid mobility: a dynamic conduit for inactivation.
AB  - Mass spectrometry and fluorescent probes have provided direct evidence that
      alkylating agents permeate the protein capsid of naked viruses and chemically
      inactivate the nucleic acid. N-acetyl-aziridine and a fluorescent alkylating
      agent, dansyl sulfonate aziridine, inactivated three different viruses, flock
      house virus, human rhinovirus-14, and foot and mouth disease virus. Mass spectral
      studies as well as fluorescent probes showed that alkylation of the genome was
      the mechanism of inactivation. Because particle integrity was not affected by
      selective alkylation (as shown by electron microscopy and sucrose gradient
      experiments), it was reasoned that the dynamic nature of the viral capsid acts as
      a conduit to the interior of the particle. Potential applications include
      fluorescent labeling for imaging viral genomes in living cells, the sterilization
      of blood products, vaccine development, and viral inactivation in vivo.

PMID- 11226231
TI  - The human mitochondrial deoxynucleotide carrier and its role in the toxicity of
      nucleoside antivirals.
AB  - The synthesis of DNA in mitochondria requires the uptake of deoxynucleotides into
      the matrix of the organelle. We have characterized a human cDNA encoding a member
      of the family of mitochondrial carriers. The protein has been overexpressed in
      bacteria and reconstituted into phospholipid vesicles where it catalyzed the
      transport of all four deoxy (d) NDPs, and, less efficiently, the corresponding
      dNTPs, in exchange for dNDPs, ADP, or ATP. It did not transport dNMPs, NMPs,
      deoxynucleosides, nucleosides, purines, or pyrimidines. The physiological role of
      this deoxynucleotide carrier is probably to supply deoxynucleotides to the
      mitochondrial matrix for conversion to triphosphates and incorporation into
      mitochondrial DNA. The protein is expressed in all human tissues that were
      examined except for placenta, in accord with such a central role. The
      deoxynucleotide carrier also transports dideoxynucleotides efficiently. It is
      likely to be medically important by providing the means of uptake into
      mitochondria of nucleoside analogs, leading to the mitochondrial impairment that
      underlies the toxic side effects of such drugs in the treatment of viral
      illnesses, including AIDS, and in cancer therapy.

PMID- 11226230
TI  - Increased mitochondrial oxidative stress in the Sod2 (+/-) mouse results in the
      age-related decline of mitochondrial function culminating in increased apoptosis.
AB  - To determine the importance of mitochondrial reactive oxygen species toxicity in
      aging and senescence, we analyzed changes in mitochondrial function with age in
      mice with partial or complete deficiencies in the mitochondrial antioxidant
      enzyme manganese superoxide dismutase (MnSOD). Liver mitochondria from homozygous
      mutant mice, with a complete deficiency in MnSOD, exhibited substantial
      respiration inhibition and marked sensitization of the mitochondrial permeability
      transition pore. Mitochondria from heterozygous mice, with a partial deficiency
      in MnSOD, showed evidence of increased proton leak, inhibition of respiration,
      and early and rapid accumulation of mitochondrial oxidative damage. Furthermore,
      chronic oxidative stress in the heterozygous mice resulted in an increased
      sensitization of the mitochondrial permeability transition pore and the premature
      induction of apoptosis, which presumably eliminates the cells with damaged
      mitochondria. Mice with normal MnSOD levels show the same age-related
      mitochondrial decline as the heterozygotes but occurring later in life. The
      premature decline in mitochondrial function in the heterozygote was associated
      with the compensatory up-regulation of oxidative phosphorylation enzyme activity.
      Thus mitochondrial reactive oxygen species production, oxidative stress,
      functional decline, and the initiation of apoptosis appear to be central
      components of the aging process.

PMID- 11226232
TI  - Gene elements that affect the longevity of rbcL sequence-containing transcripts
      in Chlamydomonas reinhardtii chloroplasts.
AB  - The chloroplast gene rbcL encodes the large subunit of the CO(2)-fixing enzyme
      ribulose-bisphosphate carboxylase. In previous work a target for photo
      accelerated degradation of Chlamydomonas reinhardtii rbcL transcripts in vivo was
      found to lie within the first 63 nucleotides, and a sequence element required for
      increasing the longevity of transcripts of rbcL-reporter genes was found to occur
      between nucleotides 170 and 350. Photo-accelerated degradation of rbcL
      transcripts has been found to require nucleotides 21 to 41. Transcript
      nucleotides lying between 329 and 334 and between 14 and 27 are essential for
      stabilizing transcripts in vivo; mutations in either region reduce the longevity
      of transcripts. It is postulated that the effectiveness of photo-accelerated
      endonuclease attacks on the nucleotide 21 to 41 region is reduced by physical
      blockage or distortion of the target sequence by interacting proteins that
      associate with nucleotides in the 14 to 27 and 329 to 334 regions of the
      transcripts. Both the nucleotide +329 to +334 stabilizing sequence of rbcL and a
      transcription enhancing sequence that lies between +126 and +170 encode well
      conserved (cyanobacteria through angiosperms) amino acid sequences; the evolution
      of expression control elements within the protein coding sequence of rbcL is
      considered.

PMID- 11226233
TI  - TRM1, a YY1-like suppressor of rbcS-m3 expression in maize mesophyll cells.
AB  - The genes rbcS and rbcL encode, respectively, the small and large subunits of the
      photosynthetic carbon dioxide fixation enzyme ribulose bisphosphate
      carboxylase/oxygenase. There is a single rbcL gene in each chloroplast
      chromosome; a family of rbcS genes is located in the nuclear genome. These two
      genes are not expressed in mesophyll cells but are in adjacent bundle-sheath
      cells of leaves of the C4 plant Zea mays. Two regions of the maize gene rbcS-m3
      are required for suppressing expression in mesophyll cells. One region is just
      beyond the translation termination site in the 3' region, and the other is
      several hundred base pairs upstream of the transcription start site. A binding
      site for a protein with limited homology to the viral, yeast, and mammalian
      transcription repressor-activator YY1 (Yin-Yang I), has now been identified in
      the 3' region. A maize gene for a protein with zinc fingers homologous to those
      of YY1 has been isolated, characterized, and expressed in Escherichia coli. The
      gene is designated trm1 (transcription repressor-maize 1). The protein TRM1 binds
      to the YY1-like site and, in addition, TRM1 binds to two sequence regions in the
      5' region of the gene that have no homology to the YY1 site. Mutagenesis or
      deletion of any of these three sequences eliminates repression of rbcS-m3
      reporter genes in mesophyll cells.

PMID- 11226234
TI  - Contributions of distinct quaternary contacts to cooperative operator binding by
      Mnt repressor.
AB  - Mnt, a tetrameric repressor encoded by bacteriophage P22, uses N-domain dimers to
      contact each half of its operator site. Experiments with a double mutant and
      structural homology with the P22 Arc repressor suggest that contacts made by Arg
      28 and stabilized by Glu-33 are largely responsible for dimer-dimer cooperativity
      in Mnt. These dimer-dimer contacts are energetically more important for operator
      binding than solution tetramerization, which is mediated by an independent C
      terminal coiled-coil domain. Indeed, once one dimer of the Mnt tetramer contacts
      an operator half site, binding of the second dimer occurs with an effective
      concentration much lower than that expected if both dimers were flexibly
      tethered. These results suggest that binding of the second dimer introduces some
      strain into the protein-DNA complex, a mechanism that could serve to limit the
      affinity of operator binding and to prevent strong binding of the Mnt tetramer to
      nonoperator sites.

PMID- 11226235
TI  - Mammalian inositol polyphosphate multikinase synthesizes inositol 1,4,5
      trisphosphate and an inositol pyrophosphate.
AB  - Using a consensus sequence in inositol phosphate kinase, we have identified and
      cloned a 44-kDa mammalian inositol phosphate kinase with broader catalytic
      capacities than any other member of the family and which we designate mammalian
      inositol phosphate multikinase (mIPMK). By phosphorylating inositol 4,5
      bisphosphate, mIPMK provides an alternative biosynthesis for inositol 1,4,5
      trisphosphate [Ins(1,4,5)P(3)]. mIPMK also can form the pyrophosphate
      disphosphoinositol tetrakisphosphate (PP-InsP(4)) from InsP(5). Additionally,
      mIPMK forms InsP(4) from Ins(1,4,5)P(3) and InsP(5) from Ins(1,3,4,5)P(4).

PMID- 11226236
TI  - Structural determinants of oxidative folding in proteins.
AB  - A method for determining the kinetic fate of structured disulfide species (i.e.,
      whether they are preferentially oxidized or reshuffle back to an unstructured
      disulfide species) is introduced. The method relies on the sensitivity of
      unstructured disulfide species to low concentrations of reducing agents. Because
      a structured des species that preferentially reshuffles generally first
      rearranges to an unstructured species, a small concentration of reduced DTT
      (e.g., 260 microM) suffices to distinguish on-pathway intermediates from dead-end
      species. We apply this method to the oxidative folding of bovine pancreatic
      ribonuclease A (RNase A) and show that des[40-95] and des[65-72] are productive
      intermediates, whereas des[26-84] and des[58-110] are metastable dead-end species
      that preferentially reshuffle. The key factor in determining the kinetic fate of
      these des species is the relative accessibility of both their thiol groups and
      disulfide bonds. Productive intermediates tend to be disulfide-secure, meaning
      that their structural fluctuations preferentially expose their thiol groups,
      while keeping their disulfide bonds buried. By contrast, dead-end species tend to
      be disulfide-insecure, in that their structural fluctuations expose their
      disulfide bonds in concert with their thiol groups. This distinction leads to
      four generic types of oxidative folding pathways. We combine these results with
      those of earlier studies to suggest a general three-stage model of oxidative
      folding of RNase A and other single-domain proteins with multiple disulfide
      bonds.

PMID- 11226237
TI  - Zinc metallothionein imported into liver mitochondria modulates respiration.
AB  - Metallothionein (MT) localizes in the intermembrane space of liver mitochondria
      as well as in the cytosol and nucleus. Incubation of intact liver mitochondria
      with physiological, micromolar concentrations of MT leads to the import of MT
      into the mitochondria where it inhibits respiration. This activity is caused by
      the N-terminal beta-domain of MT; in this system, the isolated C-terminal alpha
      domain is inactive. Free zinc inhibits respiration at concentrations commensurate
      with the zinc content of either MT or the isolated beta-domain, indicating that
      MT inhibition involves zinc delivery to mitochondria. Respiratory inhibition of
      uncoupled mitochondria identifies the electron transfer chain as the primary site
      of inhibition. The apoform of MT, thionein, is an endogenous chelating agent and
      activates zinc-inhibited respiration with a 1:1 stoichiometry ([zinc binding
      sites]/[zinc]). Carbamoylation of the lysines of MT significantly attenuates the
      inhibitory effect, suggesting that these residues are critical for the passage of
      MT through the outer mitochondrial membrane. Such an import pathway has been
      proposed for other proteins that also lack a mitochondrial targeting sequence,
      e.g., apocytochrome c, and possibly Cox17, a mitochondrial copper chaperone that
      is the only protein known so far to exhibit significant primary sequence homology
      to MT. The presence and respiratory inhibition of MT in liver, but not heart,
      mitochondria suggest a hitherto unknown biological modulating activity of MT in
      cellular respiration and energy metabolism in a tissue-specific manner.

PMID- 11226238
TI  - Fatty acids and hypolipidemic drugs regulate peroxisome proliferator-activated
      receptors alpha - and gamma-mediated gene expression via liver fatty acid binding
      protein: a signaling path to the nucleus.
AB  - Peroxisome proliferator-activated receptor alpha (PPARalpha) is a key regulator
      of lipid homeostasis in hepatocytes and target for fatty acids and hypolipidemic
      drugs. How these signaling molecules reach the nuclear receptor is not known;
      however, similarities in ligand specificity suggest the liver fatty acid binding
      protein (L-FABP) as a possible candidate. In localization studies using laser
      scanning microscopy, we show that L-FABP and PPARalpha colocalize in the nucleus
      of mouse primary hepatocytes. Furthermore, we demonstrate by pull-down assay and
      immunocoprecipitation that L-FABP interacts directly with PPARalpha. In a cell
      biological approach with the aid of a mammalian two-hybrid system, we provide
      evidence that L-FABP interacts with PPARalpha and PPARgamma but not with PPARbeta
      and retinoid X receptor-alpha by protein-protein contacts. In addition, we
      demonstrate that the observed interaction of both proteins is independent of
      ligand binding. Final and quantitative proof for L-FABP mediation was obtained in
      transactivation assays upon incubation of transiently and stably transfected
      HepG2 cells with saturated, monounsaturated, and polyunsaturated fatty acids as
      well as with hypolipidemic drugs. With all ligands applied, we observed strict
      correlation of PPARalpha and PPARgamma transactivation with intracellular
      concentrations of L-FABP. This correlation constitutes a nucleus-directed
      signaling by fatty acids and hypolipidemic drugs where L-FABP acts as a cytosolic
      gateway for these PPARalpha and PPARgamma agonists. Thus, L-FABP and the
      respective PPARs could serve as targets for nutrients and drugs to affect
      expression of PPAR-sensitive genes.

PMID- 11226239
TI  - Recent improvements in prediction of protein structure by global optimization of
      a potential energy function.
AB  - Recent improvements of a hierarchical ab initio or de novo approach for
      predicting both alpha and beta structures of proteins are described. The united
      residue energy function used in this procedure includes multibody interactions
      from a cumulant expansion of the free energy of polypeptide chains, with their
      relative weights determined by Z-score optimization. The critical initial stage
      of the hierarchical procedure involves a search of conformational space by the
      conformational space annealing (CSA) method, followed by optimization of an all
      atom model. The procedure was assessed in a recent blind test of protein
      structure prediction (CASP4). The resulting lowest-energy structures of the
      target proteins (ranging in size from 70 to 244 residues) agreed with the
      experimental structures in many respects. The entire experimental structure of a
      cyclic alpha-helical protein of 70 residues was predicted to within 4.3 A alpha
      carbon (C(alpha)) rms deviation (rmsd) whereas, for other alpha-helical proteins,
      fragments of roughly 60 residues were predicted to within 6.0 A C(alpha) rmsd.
      Whereas beta structures can now be predicted with the new procedure, the success
      rate for alpha/beta- and beta-proteins is lower than that for alpha-proteins at
      present. For the beta portions of alpha/beta structures, the C(alpha) rmsd's are
      less than 6.0 A for contiguous fragments of 30-40 residues; for one target, three
      fragments (of length 10, 23, and 28 residues, respectively) formed a compact part
      of the tertiary structure with a C(alpha) rmsd less than 6.0 A. Overall, these
      results constitute an important step toward the ab initio prediction of protein
      structure solely from the amino acid sequence.

PMID- 11226240
TI  - Destabilization of Ca2+-free gelsolin may not be responsible for proteolysis in
      Familial Amyloidosis of Finnish Type.
AB  - Mutations at position 187 in secreted gelsolin enable aberrant proteolysis at the
      172-173 and 243-244 amide bonds, affording the 71-residue amyloidogenic peptide
      deposited in Familial Amyloidosis of Finnish Type (FAF). Thermodynamic
      comparisons of two different domain 2 constructs were carried out to study
      possible effects of the mutations on proteolytic susceptibility. In the construct
      we consider to be most representative of domain 2 in the context of the full
      length protein (134-266), the D187N FAF variant is slightly destabilized relative
      to wild type (WT) under the conditions of urea denaturation, but exhibits a T(m)
      identical to WT. The D187Y variant is less stable to intermediate urea
      concentrations and exhibits a T(m) that is estimated to be approximately 5
      degrees C lower than WT (pH 7.4, Ca(2+)-free). Although the thermodynamic data
      indicate that the FAF mutations may slightly destabilize domain 2, these changes
      are probably not sufficient to shift the native to denatured state equilibrium
      enough to enable the proteolysis leading to FAF. Biophysical data indicate that
      these two FAF variants may have different native state structures and possibly
      different pathways of amyloidosis.

PMID- 11226241
TI  - Capabilities of liposomes for topological transformation.
AB  - Dynamic behaviors of liposomes caused by interactions between liposomal membranes
      and surfactant were studied by direct real-time observation by using high
      intensity dark-field microscopy. Solubilization of liposomes by surfactants is
      thought to be a catastrophic event akin to the explosion of soap bubbles in the
      air; however, the actual process has not been clarified. We studied this process
      experimentally and found that liposomes exposed to various surfactants exhibited
      unusual behavior, namely continuous shrinkage accompanied by intermittent quakes,
      release of encapsulated liposomes, opening up, and inside-out topological
      inversion.

PMID- 11226242
TI  - Dynamics and orientation of N+(CD3)3-bromoacetylcholine bound to its binding site
      on the nicotinic acetylcholine receptor.
AB  - Dynamic and structural information has been obtained for an analogue of
      acetylcholine while bound to the agonist binding site on the nicotinic
      acetylcholine receptor (nAcChoR), using wide-line deuterium solid-state NMR.
      Analysis of the deuterium lineshape obtained at various temperatures from
      unoriented nAcChoR membranes labeled with deuterated bromoacetylcholine (BAC)
      showed that the quaternary ammonium group of the ligand is well constrained
      within the agonist binding site when compared with the dynamics observed in the
      crystalline solids. This motional restriction would suggest that a high degree of
      complementarity exists between the quaternary ammonium group of the ligand and
      the protein within the agonist binding site. nAcChoR membranes were uniaxially
      oriented by isopotential centrifugation as determined by phosphorous NMR of the
      membrane phospholipids. Analysis of the deuterium NMR lineshape of these oriented
      membranes enriched with the nAcChoR labeled with N(+)(CD(3))(3)-BAC has enabled
      us to determine that the angle formed between the quaternary ammonium group of
      the BAC and the membrane normal is 42 degrees in the desensitized form of the
      receptor. This measurement allows us to orient in part the bound ligand within
      the proposed receptor binding site.

PMID- 11226243
TI  - Two different neurodegenerative diseases caused by proteins with similar
      structures.
AB  - The downstream prion-like protein (doppel, or Dpl) is a paralog of the cellular
      prion protein, PrP(C). The two proteins have approximately 25% sequence identity,
      but seem to have distinct physiologic roles. Unlike PrP(C), Dpl does not support
      prion replication; instead, overexpression of Dpl in the brain seems to cause a
      completely different neurodegenerative disease. We report the solution structure
      of a fragment of recombinant mouse Dpl (residues 26-157) containing a globular
      domain with three helices and a small amount of beta-structure. Overall, the
      topology of Dpl is very similar to that of PrP(C). Significant differences
      include a marked kink in one of the helices in Dpl, and a different orientation
      of the two short beta-strands. Although the two proteins most likely arose
      through duplication of a single ancestral gene, the relationship is now so
      distant that only the structures retain similarity; the functions have
      diversified along with the sequence.

PMID- 11226244
TI  - Transverse relaxation-optimized NMR spectroscopy with the outer membrane protein
      OmpX in dihexanoyl phosphatidylcholine micelles.
AB  - The (2)H,(13)C,(15)N-labeled, 148-residue integral membrane protein OmpX from
      Escherichia coli was reconstituted with dihexanoyl phosphatidylcholine (DHPC) in
      mixed micelles of molecular mass of about 60 kDa. Transverse relaxation-optimized
      spectroscopy (TROSY)-type triple resonance NMR experiments and TROSY-type nuclear
      Overhauser enhancement spectra were recorded in 2 mM aqueous solutions of these
      mixed micelles at pH 6.8 and 30 degrees C. Complete sequence-specific NMR
      assignments for the polypeptide backbone thus have been obtained. The (13)C
      chemical shifts and the nuclear Overhauser effect data then resulted in the
      identification of the regular secondary structure elements of OmpX/DHPC in
      solution and in the collection of an input of conformational constraints for the
      computation of the global fold of the protein. The same type of polypeptide
      backbone fold is observed in the presently determined solution structure and the
      previously reported crystal structure of OmpX determined in the presence of the
      detergent n-octyltetraoxyethylene. Further structure refinement will have to rely
      on the additional resonance assignment of partially or fully protonated amino
      acid side chains, but the present data already demonstrate that relaxation
      optimized NMR techniques open novel avenues for studies of structure and function
      of integral membrane proteins.

PMID- 11226245
TI  - An unusual pathway of excitation energy deactivation in carotenoids: singlet-to
      triplet conversion on an ultrafast timescale in a photosynthetic antenna.
AB  - Carotenoids are important biomolecules that are ubiquitous in nature and find
      widespread application in medicine. In photosynthesis, they have a large role in
      light harvesting (LH) and photoprotection. They exert their LH function by
      donating their excited singlet state to nearby (bacterio)chlorophyll molecules.
      In photosynthetic bacteria, the efficiency of this energy transfer process can be
      as low as 30%. Here, we present evidence that an unusual pathway of excited state
      relaxation in carotenoids underlies this poor LH function, by which carotenoid
      triplet states are generated directly from carotenoid singlet states. This
      pathway, operative on a femtosecond and picosecond timescale, involves an
      intermediate state, which we identify as a new, hitherto uncharacterized
      carotenoid singlet excited state. In LH complex-bound carotenoids, this state is
      the precursor on the reaction pathway to the triplet state, whereas in extracted
      carotenoids in solution, this state returns to the singlet ground state without
      forming any triplets. We discuss the possible identity of this excited state and
      argue that fission of the singlet state into a pair of triplet states on
      individual carotenoid molecules constitutes the mechanism by which the triplets
      are generated. This is, to our knowledge, the first ever direct observation of a
      singlet-to-triplet conversion process on an ultrafast timescale in a
      photosynthetic antenna.

PMID- 11226246
TI  - The role of structure, energy landscape, dynamics, and allostery in the enzymatic
      function of myoglobin.
AB  - The grail of protein science is the connection between structure and function.
      For myoglobin (Mb) this goal is close. Described as only a passive dioxygen
      storage protein in texts, we argue here that Mb is actually an allosteric enzyme
      that can catalyze reactions among small molecules. Studies of the structural,
      spectroscopic, and kinetic properties of Mb lead to a model that relates
      structure, energy landscape, dynamics, and function. Mb functions as a miniature
      chemical reactor, concentrating and orienting diatomic molecules such as NO, CO,
      O(2), and H(2)O(2) in highly conserved internal cavities. Reactions can be
      controlled because Mb exists in distinct taxonomic substates with different
      catalytic properties and connectivities of internal cavities.

PMID- 11226247
TI  - An amyloid-forming peptide from the yeast prion Sup35 reveals a dehydrated beta
      sheet structure for amyloid.
AB  - X-ray diffraction and other biophysical tools reveal features of the atomic
      structure of an amyloid-like crystal. Sup35, a prion-like protein in yeast, forms
      fibrillar amyloid assemblies intrinsic to its prion function. We have identified
      a polar peptide from the N-terminal prion-determining domain of Sup35 that
      exhibits the amyloid properties of full-length Sup35, including cooperative
      kinetics of aggregation, fibril formation, binding of the dye Congo red, and the
      characteristic cross-beta x-ray diffraction pattern. Microcrystals of this
      peptide also share the principal properties of the fibrillar amyloid, including a
      highly stable, beta-sheet-rich structure and the binding of Congo red. The x-ray
      powder pattern of the microcrystals, extending to 0.9-A resolution, yields the
      unit cell dimensions of the well-ordered structure. These dimensions restrict
      possible atomic models of this amyloid-like structure and demonstrate that it
      forms packed, parallel-stranded beta-sheets. The unusually high density of the
      crystals shows that the packed beta-sheets are dehydrated, despite the polar
      character of the side chains. These results suggest that amyloid is a highly
      intermolecularly bonded, dehydrated array of densely packed beta-sheets. This dry
      beta-sheet could form as Sup35 partially unfolds to expose the peptide,
      permitting it to hydrogen-bond to the same peptide of other Sup35 molecules. The
      implication is that amyloid-forming units may be short segments of proteins,
      exposed for interactions by partial unfolding.

PMID- 11226248
TI  - Presenilin-1 binds cytoplasmic epithelial cadherin, inhibits cadherin/p120
      association, and regulates stability and function of the cadherin/catenin
      adhesion complex.
AB  - Here we show that presenilin-1 (PS1), a protein involved in Alzheimer's disease,
      binds directly to epithelial cadherin (E-cadherin). This binding is mediated by
      the large cytoplasmic loop of PS1 and requires the membrane-proximal cytoplasmic
      sequence 604-615 of mature E-cadherin. This sequence is also required for E
      cadherin binding of protein p120, a known regulator of cadherin-mediated cell
      adhesion. Using wild-type and PS1 knockout cells, we found that increasing PS1
      levels suppresses p120/E-cadherin binding, and increasing p120 levels suppresses
      PS1/E-cadherin binding. Thus PS1 and p120 bind to and mutually compete for
      cellular E-cadherin. Furthermore, PS1 stimulates E-cadherin binding to beta- and
      gamma-catenin, promotes cytoskeletal association of the cadherin/catenin
      complexes, and increases Ca(2+)-dependent cell-cell aggregation. Remarkably, PS1
      familial Alzheimer disease mutant DeltaE9 increased neither the levels of
      cadherin/catenin complexes nor cell aggregation, suggesting that this familial
      Alzheimer disease mutation interferes with cadherin-based cell-cell adhesion.
      These data identify PS1 as an E-cadherin-binding protein and a regulator of E
      cadherin function in vivo.

PMID- 11226249
TI  - An isolated, surface-expressed I domain of the integrin alphaLbeta2 is sufficient
      for strong adhesive function when locked in the open conformation with a
      disulfide bond.
AB  - We introduced disulfide bonds to lock the integrin alphaLbeta2 I domain in
      predicted open, ligand binding or closed, nonbinding conformations. Transfectants
      expressing alphaLbeta2 heterodimers containing locked-open but not locked-closed
      or wild-type I domains constitutively adhered to intercellular adhesion molecule
      1 (ICAM-1) substrates. Locking the I domain closed abolished constitutive and
      activatable adhesion. The isolated locked-open I domain bound as well as the
      activated alphaLbeta2 heterodimer, and binding was abolished by reduction of the
      disulfide. Lovastatin, which binds under the conformationally mobile C-terminal
      alpha-helix of the I domain, inhibited binding to ICAM-1 by alphaLbeta2 with wild
      type, but not locked-open I domains. These data establish the importance of
      conformational change in the alphaL I domain for adhesive function and show that
      this domain is sufficient for full adhesive activity.

PMID- 11226250
TI  - Locking in alternate conformations of the integrin alphaLbeta2 I domain with
      disulfide bonds reveals functional relationships among integrin domains.
AB  - We used integrin alphaLbeta2 heterodimers containing I domains locked open
      (active) or closed (inactive) with disulfide bonds to investigate regulatory
      interactions among domains in integrins. mAbs to the alphaL I domain and beta2 I
      like domain inhibit adhesion of wild-type alphaLbeta2 to intercellular adhesion
      molecule-1. However, with alphaLbeta2 containing a locked open I domain, mAbs to
      the I domain were subdivided into subsets (i) that did not inhibit, and thus
      appear to inhibit by favoring the closed conformation, and (ii) that did inhibit,
      and thus appear to bind to the ligand binding site. Furthermore, alphaLbeta2
      containing a locked open I domain was completely resistant to inhibition by mAbs
      to the beta2 I-like domain, but became fully susceptible to inhibition after
      disulfide reduction with DTT. This finding suggests that the I-like domain
      indirectly contributes to ligand binding by regulating opening of the I domain in
      wild-type alphaLbeta2. Conversely, locking the I domain closed partially
      restrained conformational change of the I-like domain by Mn(2+), as measured with
      mAb m24, which we map here to the beta2 I-like domain. By contrast, locking the I
      domain closed or open did not affect constitutive or Mn(2+)-induced exposure of
      the KIM127 epitope in the beta2 stalk region. Furthermore, locked open I domains,
      in alphaLbeta2 complexes or expressed in isolation on the cell surface, bound to
      intercellular adhesion molecule-1 equivalently in Mg(2+) and Mn(2+). These
      results suggest that Mn(2+) activates alphaLbeta2 by binding to a site other than
      the I domain, most likely the I-like domain of beta2.

PMID- 11226252
TI  - Kinetics of protein import into isolated Xenopus oocyte nuclei.
AB  - An in vitro assay for nucleocytoplasmic transport was established in which signal
      dependent protein import is reproduced faithfully by isolated purified nuclei.
      The assay permits the precise quantification of import kinetics and the
      discrimination between translocation through the nuclear envelope and
      intranuclear transport. Nuclei were manually isolated from Xenopus oocytes and
      after manual purification incubated with a medium containing a green fluorescent
      transport substrate, karyopherins alpha2 and beta1, a red fluorescent control
      substrate, an energy mix and, for keeping an osmotic balance, 20% (wt/vol) BSA.
      Import of transport substrates into the nucleus and exclusion of the control
      substrate were monitored simultaneously by two-color confocal microscopy. Two
      widely differing import substrates were used: the recombinant protein P4K [480
      kDa, four nuclear localization sequences (NLSs) per P4K tetramer], and NLS-BSA
      (90 kDa, 15 NLSs). The measurements suggested that import, at the specific
      conditions used in this study, consisted of two consecutive processes: (i) the
      rapid equilibration of the concentration difference across the nuclear envelope,
      a process involving binding and translocation of substrate by the nuclear pore
      complex, and (ii) the dissipation of the intranuclear concentration difference by
      diffusion.

PMID- 11226251
TI  - Organellar relationships in the Golgi region of the pancreatic beta cell line,
      HIT-T15, visualized by high resolution electron tomography.
AB  - The positional relationships among all of the visible organelles in a densely
      packed region of cytoplasm from an insulin secreting, cultured mammalian cell
      have been analyzed in three dimensions (3-D) at approximately 6 nm resolution.
      Part of a fast frozen/freeze-substituted HIT-T15 cell that included a large
      portion of the Golgi ribbon was reconstructed in 3-D by electron tomography. The
      reconstructed volume (3.1 x 3.2 x 1.2 microm(3)) allowed sites of interaction
      between organelles, and between microtubules and organellar membranes, to be
      accurately defined in 3-D and quantitatively analyzed by spatial density
      analyses. Our data confirm that the Golgi in an interphase mammalian cell is a
      single, ribbon-like organelle composed of stacks of flattened cisternae
      punctuated by openings of various sizes [Rambourg, A., Clermont, Y., & Hermo, L.
      (1979) Am. J. Anat. 154, 455-476]. The data also show that the endoplasmic
      reticulum (ER) is a single continuous compartment that forms close contacts with
      mitochondria, multiple trans Golgi cisternae, and compartments of the endo
      lysosomal system. This ER traverses the Golgi ribbon from one side to the other
      via cisternal openings. Microtubules form close, non-random associations with the
      cis Golgi, the ER, and endo-lysosomal compartments. Despite the dense packing of
      organelles in this Golgi region, approximately 66% of the reconstructed volume is
      calculated to represent cytoplasmic matrix. We relate the intimacy of structural
      associations between organelles in the Golgi region, as quantified by spatial
      density analyses, to biochemical mechanisms for membrane trafficking and
      organellar communication in mammalian cells.

PMID- 11226253
TI  - ARF-GEP(100), a guanine nucleotide-exchange protein for ADP-ribosylation factor
      6.
AB  - A human cDNA encoding an 841-aa guanine nucleotide-exchange protein (GEP) for ADP
      ribosylation factors (ARFs), named ARF-GEP(100), which contains a Sec7 domain, a
      pleckstrin homology (PH)-like domain, and an incomplete IQ-motif, was identified.
      On Northern blot analysis of human tissues, a approximately 8-kb mRNA that
      hybridized with an ARF-GEP(100) cDNA was abundant in peripheral blood leukocytes,
      brain, and spleen. ARF-GEP(100) accelerated [(35)S]GTPgammaS binding to ARF1
      (class I) and ARF5 (class II) 2- to 3-fold, and to ARF6 (class III) ca. 12-fold.
      The ARF-GEP(100) Sec7 domain contains Asp(543) and Met(555), corresponding to
      residues associated with sensitivity to the inhibitory effect of the fungal
      metabolite brefeldin A (BFA) in yeast Sec7, but also Phe(535) and Ala(536),
      associated with BFA-insensitivity. The PH-like domain differs greatly from those
      of other ARF GEPs in regions involved in phospholipid binding. Consistent with
      its structure, ARF-GEP(100) activity was not affected by BFA or phospholipids.
      After subcellular fractionation of cultured T98G human glioblastoma cells, ARF6
      was almost entirely in the crude membrane fraction, whereas ARF-GEP(100), a 100
      kDa protein detected with antipeptide antibodies, was cytosolic. On
      immunofluorescence microscopy, both proteins had a punctate pattern of
      distribution throughout the cells, with apparent colocalization only in
      peripheral areas. The coarse punctate distribution of EEA-1 in regions nearer the
      nucleus appeared to coincide with that of ARF-GEP(100) in those areas. No similar
      coincidence of ARF-GEP(100) with AP-1, AP-2, catenin, LAMP-1, or 58K was
      observed. The new human BFA-insensitive GEP may function with ARF6 in specific
      endocytic processes.

PMID- 11226254
TI  - Identification of the endogenous smooth muscle myosin phosphatase-associated
      kinase.
AB  - Ca(2+) sensitization of smooth muscle contraction involves inhibition of myosin
      light chain phosphatase (SMPP-1M) and enhanced myosin light chain
      phosphorylation. Inhibition of SMPP-1M is modulated through phosphorylation of
      the myosin targeting subunit (MYPT1) by either Rho-associated kinase (ROK) or an
      unknown SMPP-1M-associated kinase. Activated ROK is predominantly membrane
      associated and its putative substrate, SMPP-1M, is mainly myofibrillar
      associated. This raises a conundrum about the mechanism of interaction between
      these enzymes. We present ZIP-like kinase, identified by "mixed-peptide" Edman
      sequencing after affinity purification, as the previously unidentified SMPP-1M
      associated kinase. ZIP-like kinase was shown to associate with MYPT1 and
      phosphorylate the inhibitory site in intact smooth muscle. Phosphorylation of ZIP
      like kinase was associated with an increase in kinase activity during carbachol
      stimulation, suggesting that the enzyme may be a terminal member of a Ca(2+)
      sensitizing kinase cascade.

PMID- 11226256
TI  - Analysis of endoplasmic reticulum trafficking signals by combinatorial screening
      in mammalian cells.
AB  - To improve the accuracy of predicting membrane protein sorting signals, we
      developed a general methodology for defining trafficking signal consensus
      sequences in the environment of the living cell. Our approach uses retroviral
      gene transfer to create combinatorial expression libraries of trafficking signal
      variants in mammalian cells, flow cytometry to sort cells based on trafficking
      phenotype, and quantitative trafficking assays to measure the efficacy of
      individual signals. Using this strategy to analyze arginine- and lysine-based
      endoplasmic reticulum localization signals, we demonstrate that small changes in
      the local sequence context dramatically alter signal strength, generating a broad
      spectrum of trafficking phenotypes. Finally, using sequences from our screen, we
      found that the potency of di-lysine, but not di-arginine, mediated endoplasmic
      reticulum localization was correlated with the strength of interaction with alpha
      COP.

PMID- 11226255
TI  - FKBP12, the 12-kDa FK506-binding protein, is a physiologic regulator of the cell
      cycle.
AB  - FKBP12, the 12-kDa FK506-binding protein, is a ubiquitous abundant protein that
      acts as a receptor for the immunosuppressant drug FK506, binds tightly to
      intracellular calcium release channels and to the transforming growth factor beta
      (TGF-beta) type I receptor. We now demonstrate that cells from FKBP12-deficient
      (FKBP12(-/-)) mice manifest cell cycle arrest in G(1) phase and that these cells
      can be rescued by FKBP12 transfection. This arrest is mediated by marked
      augmentation of p21(WAF1/CIP1) levels, which cannot be further augmented by TGF
      beta1. The p21 up-regulation and cell cycle arrest derive from the overactivity
      of TGF-beta receptor signaling, which is normally inhibited by FKBP12. Cell cycle
      arrest is prevented by transfection with a dominant-negative TGF-beta receptor
      construct. TGF-beta receptor signaling to gene expression can be mediated by
      SMAD, p38, and ERK/MAP kinase (extracellular signal-regulated kinase/mitogen
      activated protein kinase) pathways. SMAD signaling is down-regulated in FKBP12(-/
      ) cells. Inhibition of ERK/MAP kinase fails to affect p21 up-regulation. By
      contrast, activated phosphorylated p38 is markedly augmented in FKBP12(-/-) cells
      and the p21 up-regulation is prevented by an inhibitor of p38. Thus, FKBP12 is a
      physiologic regulator of cell cycle acting by normally down-regulating TGF-beta
      receptor signaling.

PMID- 11226257
TI  - Spatiotemporal dynamics of guanosine 3',5'-cyclic monophosphate revealed by a
      genetically encoded, fluorescent indicator.
AB  - To investigate the dynamics of guanosine 3',5'-cyclic monophosphate (cGMP) in
      single living cells, we constructed genetically encoded, fluorescent cGMP
      indicators by bracketing cGMP-dependent protein kinase (cGPK), minus residues 1
      77, between cyan and yellow mutants of green fluorescent protein. cGMP decreased
      fluorescence resonance energy transfer (FRET) and increased the ratio of cyan to
      yellow emissions by up to 1.5-fold with apparent dissociation constants of
      approximately 2 microM and >100:1 selectivity for cGMP over cAMP. To eliminate
      constitutive kinase activity, Thr(516) of cGPK was mutated to Ala. Emission ratio
      imaging of the indicators transfected into rat fetal lung fibroblast (RFL)-6
      showed cGMP transients resulting from activation of soluble and particulate
      guanylyl cyclase, respectively, by nitric oxide (NO) and C-type natriuretic
      peptide (CNP). Whereas all naive cells tested responded to CNP, only 68%
      responded to NO. Both sets of signals showed large and variable (0.5-4 min)
      latencies. The phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine
      (IBMX) did not elevate cGMP on its own but consistently amplified responses to NO
      or CNP, suggesting that basal activity of guanylate cyclase is very low and
      emphasizing the importance of PDEs in cGMP recycling. A fraction of RFL cells
      showed slowly propagating tides of cGMP spreading across the cell in response to
      delocalized application of NO. Biolistically transfected Purkinje neurons showed
      cGMP responses to parallel fiber activity and NO donors, confirming that single
      cell increases in cGMP occur under conditions appropriate to cause synaptic
      plasticity.

PMID- 11226258
TI  - IL-4 inhibits osteoclast formation through a direct action on osteoclast
      precursors via peroxisome proliferator-activated receptor gamma 1.
AB  - IL-4 is a pleiotropic immune cytokine secreted by activated T(H)2 cells that
      inhibits bone resorption both in vitro and in vivo. The cellular targets of IL-4
      action as well as its intracellular mechanism of action remain to be determined.
      We show here that IL-4 inhibits receptor activator of NF-kappaB ligand-induced
      osteoclast differentiation through an action on osteoclast precursors that is
      independent of stromal cells. Interestingly, this inhibitory effect can be
      mimicked by both natural as well as synthetic peroxisome proliferator-activated
      receptor gamma1 (PPARgamma1) ligands and can be blocked by the irreversible
      PPARgamma antagonist GW 9662. These findings suggest that the actions of IL-4 on
      osteoclast differentiation are mediated by PPARgamma1, an interpretation
      strengthened by the observation that IL-4 can activate a PPARgamma1-sensitive
      luciferase reporter gene in RAW264.7 cells. We also show that inhibitors of
      enzymes such as 12/15-lipoxygenase and the cyclooxygenases that produce known
      PPARgamma1 ligands do not abrogate the IL-4 effect. These findings, together with
      the observation that bone marrow cells from 12/15-lipoxygenase-deficient mice
      retain sensitivity to IL-4, suggest that the cytokine may induce novel PPARgamma1
      ligands. Our results reveal that PPARgamma1 plays an important role in the
      suppression of osteoclast formation by IL-4 and may explain the beneficial
      effects of the thiazolidinedione class of PPARgamma1 ligands on bone loss in
      diabetic patients.

PMID- 11226260
TI  - Identification and dissection of an enhancer controlling epithelial gene
      expression in skin.
AB  - Keratins 14 and 5 are the structural hallmarks of the basal keratinocytes of the
      epidermis and outer root sheath (ORS) of the hair follicle. Their genes are
      controlled in a tissue-specific manner and thus serve as useful tools to
      elucidate the regulatory mechanisms involved in keratinocyte-specific
      transcription. Previously we identified several keratinocyte-specific DNase I
      hypersensitive sites (HSs) in the 5' regulatory sequences of the K14 gene and
      showed that a 700-bp regulatory domain encompassing HSs II and III can confer
      epidermal and ORS-specific gene expression in transgenic mice in vivo. Although
      HS II harbored much of the transactivation activity in vitro, it was not
      sufficient to restrict expression to keratinocytes in vivo. We now explore the HS
      III regulatory element. Surprisingly, this element on its own confers gene
      expression to the keratinocytes of the inner root sheath (IRS) of the hair
      follicle, whereas a 275-bp DNA fragment containing both HSs II and III shifts the
      expression from the IRS to the basal keratinocytes and ORS in vivo.
      Electrophoretic mobility-shift assays and mutational studies of HSs III reveal a
      role for CACCC-box binding proteins, Sp1 family members, and other factors adding
      to the list of previously described factors that are involved in keratinocyte
      specific gene expression. These studies highlight a cooperative interaction of
      the two HSs domains and strengthen the importance of combinatorial play of
      transcription factors that govern keratinocyte-specific gene regulation.

PMID- 11226259
TI  - Activation and targeting of extracellular signal-regulated kinases by beta
      arrestin scaffolds.
AB  - Using both confocal immunofluorescence microscopy and biochemical approaches, we
      have examined the role of beta-arrestins in the activation and targeting of
      extracellular signal-regulated kinase 2 (ERK2) following stimulation of
      angiotensin II type 1a receptors (AT1aR). In HEK-293 cells expressing
      hemagglutinin-tagged AT1aR, angiotensin stimulation triggered beta-arrestin-2
      binding to the receptor and internalization of AT1aR-beta-arrestin complexes.
      Using red fluorescent protein-tagged ERK2 to track the subcellular distribution
      of ERK2, we found that angiotensin treatment caused the redistribution of
      activated ERK2 into endosomal vesicles that also contained AT1aR-beta-arrestin
      complexes. This targeting of ERK2 reflects the formation of multiprotein
      complexes containing AT1aR, beta-arrestin-2, and the component kinases of the ERK
      cascade, cRaf-1, MEK1, and ERK2. Myc-tagged cRaf-1, MEK1, and green fluorescent
      protein-tagged ERK2 coprecipitated with Flag-tagged beta-arrestin-2 from
      transfected COS-7 cells. Coprecipitation of cRaf-1 with beta-arrestin-2 was
      independent of MEK1 and ERK2, whereas the coprecipitation of MEK1 and ERK2 with
      beta-arrestin-2 was significantly enhanced in the presence of overexpressed cRaf
      1, suggesting that binding of cRaf-1 to beta-arrestin facilitates the assembly of
      a cRaf-1, MEK1, ERK2 complex. The phosphorylation of ERK2 in beta-arrestin
      complexes was markedly enhanced by coexpression of cRaf-1, and this effect is
      blocked by expression of a catalytically inactive dominant inhibitory mutant of
      MEK1. Stimulation with angiotensin increased the binding of both cRaf-1 and ERK2
      to beta-arrestin-2, and the association of beta-arrestin-2, cRaf-1, and ERK2 with
      AT1aR. These data suggest that beta-arrestins function both as scaffolds to
      enhance cRaf-1 and MEK-dependent activation of ERK2, and as targeting proteins
      that direct activated ERK to specific subcellular locations.

PMID- 11226261
TI  - Production of zebrafish germ-line chimeras from embryo cell cultures.
AB  - Although the zebrafish possesses many characteristics that make it a valuable
      model for genetic studies of vertebrate development, one deficiency of this model
      system is the absence of methods for cell-mediated gene transfer and targeted
      gene inactivation. In mice, embryonic stem cell cultures are routinely used for
      gene transfer and provide the advantage of in vitro selection for rare events
      such as homologous recombination and targeted mutation. Transgenic animals
      possessing a mutated copy of the targeted gene are generated when the selected
      cells contribute to the germ line of a chimeric embryo. Although zebrafish embryo
      cell cultures that exhibit characteristics of embryonic stem cells have been
      described, successful contribution of the cells to the germ-cell lineage of a
      host embryo has not been reported. In this study, we demonstrate that short-term
      zebrafish embryo cell cultures maintained in the presence of cells from a rainbow
      trout spleen cell line (RTS34st) are able to produce germ-line chimeras when
      introduced into a host embryo. Messenger RNA encoding the primordial germ-cell
      marker, vasa, was present for more than 30 days in embryo cells cocultured with
      RTS34st cells or their conditioned medium and disappeared by 5 days in the
      absence of the spleen cells. The RTS34st cells also inhibited melanocyte and
      neuronal cell differentiation in the embryo cell cultures. These results suggest
      that the RTS34st splenic-stromal cell line will be a valuable tool in the
      development of a cell-based gene transfer approach to targeted gene inactivation
      in zebrafish.

PMID- 11226262
TI  - An efficient system for conditional gene expression in embryonic stem cells and
      in their in vitro and in vivo differentiated derivatives.
AB  - We have developed a universally applicable system for conditional gene expression
      in embryonic stem (ES) cells that relies on tamoxifen-dependent Cre recombinase
      loxP site-mediated recombination and bicistronic gene-trap expression vectors
      that allow transgene expression from endogenous cellular promoters. Two vectors
      were introduced into the genome of recipient ES cells, successively: (i) a
      bicistronic gene-trap vector encoding the beta-galactosidase/neo(R) fusion
      protein and the Cre-ER(T2) (Cre recombinase fused to a mutated ligand-binding
      domain of the human estrogen receptor) and (ii) a bicistronic gene-trap vector
      encoding the hygro(R) protein and the human alkaline phosphatase (hAP), the
      expression of which is prevented by tandemly repeated stop-of-transcription
      sequences flanked by loxP sites. In selected clones, hAP expression was shown to
      be regulated accurately by 4'hydroxy-tamoxifen. Strict hormone-dependent
      expression of hAP was achieved (i) in vitro in undifferentiated ES cells and
      embryoid bodies, (ii) in vivo in virtually all the tissues of the 10-day-old
      chimeric fetus (after injection of 4'hydroxy-tamoxifen to foster mothers), and
      (iii) ex vivo in primary embryonic fibroblasts isolated from chimeric fetuses.
      Therefore, this approach can be applied to drive conditional expression of
      virtually any transgene in a large variety of cell types, both in vitro and in
      vivo.

PMID- 11226264
TI  - Effects of elevated atmospheric CO2 concentration on leaf dark respiration of
      Xanthium strumarium in light and in darkness.
AB  - Leaf dark respiration (R) is an important component of plant carbon balance, but
      the effects of rising atmospheric CO(2) on leaf R during illumination are largely
      unknown. We studied the effects of elevated CO(2) on leaf R in light (R(L)) and
      in darkness (R(D)) in Xanthium strumarium at different developmental stages. Leaf
      R(L) was estimated by using the Kok method, whereas leaf R(D) was measured as the
      rate of CO(2) efflux at zero light. Leaf R(L) and R(D) were significantly higher
      at elevated than at ambient CO(2) throughout the growing period. Elevated CO(2)
      increased the ratio of leaf R(L) to net photosynthesis at saturated light
      (A(max)) when plants were young and also after flowering, but the ratio of leaf
      R(D) to A(max) was unaffected by CO(2) levels. Leaf R(N) was significantly higher
      at the beginning but significantly lower at the end of the growing period in
      elevated CO(2)-grown plants. The ratio of leaf R(L) to R(D) was used to estimate
      the effect of light on leaf R during the day. We found that light inhibited leaf
      R at both CO(2) concentrations but to a lesser degree for elevated (17-24%) than
      for ambient (29-35%) CO(2)-grown plants, presumably because elevated CO(2)-grown
      plants had a higher demand for energy and carbon skeletons than ambient CO(2)
      grown plants in light. Our results suggest that using the CO(2) efflux rate,
      determined by shading leaves during the day, as a measure for leaf R is likely to
      underestimate carbon loss from elevated CO(2)-grown plants.

PMID- 11226263
TI  - Plant growth in elevated CO2 alters mitochondrial number and chloroplast fine
      structure.
AB  - With increasing interest in the effects of elevated atmospheric CO(2) on plant
      growth and the global carbon balance, there is a need for greater understanding
      of how plants respond to variations in atmospheric partial pressure of CO(2). Our
      research shows that elevated CO(2) produces significant fine structural changes
      in major cellular organelles that appear to be an important component of the
      metabolic responses of plants to this global change. Nine species (representing
      seven plant families) in several experimental facilities with different CO(2)
      dosing technologies were examined. Growth in elevated CO(2) increased numbers of
      mitochondria per unit cell area by 1.3-2.4 times the number in control plants
      grown in lower CO(2) and produced a statistically significant increase in the
      amount of chloroplast stroma (nonappressed) thylakoid membranes compared with
      those in lower CO(2) treatments. There was no observable change in size of the
      mitochondria. However, in contrast to the CO(2) effect on mitochondrial number,
      elevated CO(2) promoted a decrease in the rate of mass-based dark respiration.
      These changes may reflect a major shift in plant metabolism and energy balance
      that may help to explain enhanced plant productivity in response to elevated
      atmospheric CO(2) concentrations.

PMID- 11226265
TI  - Paleoclimate and Amerindians: evidence from stable isotopes and atmospheric
      circulation.
AB  - Two Amerindian demographic shifts are attributed to climate change in the
      northwest plains of North America: at approximately 11,000 calendar years before
      present (yr BP), Amerindian culture apparently split into foothills-mountains vs.
      plains biomes; and from 8,000-5,000 yr BP, scarce archaeological sites on the
      open plains suggest emigration during xeric "Altithermal" conditions. We
      reconstructed paleoclimates from stable isotopes in prehistoric bison bone and
      relations between weather and fractions of C(4) plants in forage. Further, we
      developed a climate-change model that synthesized stable isotope, existing
      qualitative evidence (e.g., palynological, erosional), and global climate
      mechanisms affecting this midlatitude region. Our isotope data indicate
      significant warming from approximately 12,400 to 11,900 yr BP, supporting climate
      driven cultural separation. However, isotope evidence of apparently wet, warm
      conditions at 7,300 yr BP refutes emigration to avoid xeric conditions. Scarcity
      of archaeological sites is best explained by rapid climate fluctuations after
      catastrophic draining of the Laurentide Lakes, which disrupted North Atlantic
      Deep Water production and subsequently altered monsoonal inputs to the open
      plains.

PMID- 11226266
TI  - Predator-induced stress makes the pesticide carbaryl more deadly to gray treefrog
      tadpoles (Hyla versicolor).
AB  - Global declines in amphibians likely have multiple causes, including widespread
      pesticide use. Our knowledge of pesticide effects on amphibians is largely
      limited to short-term (4-d) toxicity tests conducted under highly artificial
      conditions to determine lethal concentrations (LC50). We found that if we used
      slightly longer exposure times (10-16 d), low concentrations of the pesticide
      carbaryl (3-4% of LC50(4-d)) killed 10-60% of gray treefrog (Hyla versicolor)
      tadpoles. If predatory cues also were present, the pesticide became 2-4 times
      more lethal, killing 60-98% of tadpoles. Thus, under more realistic conditions of
      increased exposure times and predatory stress, current application rates for
      carbaryl can potentially devastate gray treefrog populations. Further, because
      predator-induced stress is ubiquitous in animals and carbaryl's mode of action is
      common to many pesticides, these negative impacts may be widespread in nature.

PMID- 11226267
TI  - Estimation of divergence times from multiprotein sequences for a few mammalian
      species and several distantly related organisms.
AB  - When many protein sequences are available for estimating the time of divergence
      between two species, it is customary to estimate the time for each protein
      separately and then use the average for all proteins as the final estimate.
      However, it can be shown that this estimate generally has an upward bias, and
      that an unbiased estimate is obtained by using distances based on concatenated
      sequences. We have shown that two concatenation-based distances, i.e., average
      gamma distance weighted with sequence length (d(2)) and multiprotein gamma
      distance (d(3)), generally give more satisfactory results than other
      concatenation-based distances. Using these two distance measures for 104 protein
      sequences, we estimated the time of divergence between mice and rats to be
      approximately 33 million years ago. Similarly, the time of divergence between
      humans and rodents was estimated to be approximately 96 million years ago. We
      also investigated the dependency of time estimates on statistical methods and
      various assumptions made by using sequence data from eubacteria, protists,
      plants, fungi, and animals. Our best estimates of the times of divergence between
      eubacteria and eukaryotes, between protists and other eukaryotes, and between
      plants, fungi, and animals were 3, 1.7, and 1.3 billion years ago, respectively.
      However, estimates of ancient divergence times are subject to a substantial
      amount of error caused by uncertainty of the molecular clock, horizontal gene
      transfer, errors in sequence alignments, etc.

PMID- 11226268
TI  - Phylogeny of genes for secretion NTPases: identification of the widespread tadA
      subfamily and development of a diagnostic key for gene classification.
AB  - Macromolecular transport systems in bacteria currently are classified by function
      and sequence comparisons into five basic types. In this classification system,
      type II and type IV secretion systems both possess members of a superfamily of
      genes for putative NTP hydrolase (NTPase) proteins that are strikingly similar in
      structure, function, and sequence. These include VirB11, TrbB, TraG, GspE, PilB,
      PilT, and ComG1. The predicted protein product of tadA, a recently discovered
      gene required for tenacious adherence of Actinobacillus actinomycetemcomitans,
      also has significant sequence similarity to members of this superfamily and to
      several unclassified and uncharacterized gene products of both Archaea and
      Bacteria. To understand the relationship of tadA and tadA-like genes to those
      encoding the putative NTPases of type II/IV secretion, we used a phylogenetic
      approach to obtain a genealogy of 148 NTPase genes and reconstruct a scenario of
      gene superfamily evolution. In this phylogeny, clear distinctions can be made
      between type II and type IV families and their constituent subfamilies. In
      addition, the subgroup containing tadA constitutes a novel and extremely
      widespread subfamily of the family encompassing all putative NTPases of type IV
      secretion systems. We report diagnostic amino acid residue positions for each
      major monophyletic family and subfamily in the phylogenetic tree, and we propose
      an easy method for precisely classifying and naming putative NTPase genes based
      on phylogeny. This molecular key-based method can be applied to other gene
      superfamilies and represents a valuable tool for genome analysis.

PMID- 11226270
TI  - Role of the F-box protein Skp2 in lymphomagenesis.
AB  - The F-box protein Skp2 (S-phase kinase-associated protein 2) positively regulates
      the G(1)-S transition by controlling the stability of several G(1) regulators,
      such as the cell cycle inhibitor p27. We show here that Skp2 expression
      correlates directly with grade of malignancy and inversely with p27 levels in
      human lymphomas. To directly evaluate the potential of Skp2 to deregulate growth
      in vivo, we generated transgenic mice expressing Skp2 targeted to the T-lymphoid
      lineage as well as double transgenic mice coexpressing Skp2 and activated N-Ras.
      A strong cooperative effect between these two transgenes induced T cell lymphomas
      with shorter latency and higher penetrance, leading to significantly decreased
      survival when compared with control and single transgenic animals. Furthermore,
      lymphomas of Nras single transgenic animals often expressed higher levels of
      endogenous Skp2 than tumors of double transgenic mice. This study provides
      evidence of a role for an F-box protein in oncogenesis and establishes SKP2 as a
      protooncogene causally involved in the pathogenesis of lymphomas.

PMID- 11226269
TI  - Positive Darwinian selection drives the evolution of several female reproductive
      proteins in mammals.
AB  - Rapid evolution driven by positive Darwinian selection is a recurrent theme in
      male reproductive protein evolution. In contrast, positive selection has never
      been demonstrated for female reproductive proteins. Here, we perform phylogeny
      based tests on three female mammalian fertilization proteins and demonstrate
      positive selection promoting their divergence. Two of these female fertilization
      proteins, the zona pellucida glycoproteins ZP2 and ZP3, are part of the mammalian
      egg coat. Several sites identified in ZP3 as likely to be under positive
      selection are located in a region previously demonstrated to be involved in
      species-specific sperm-egg interaction, suggesting the selective pressure is
      related to male-female interaction. The results provide long-sought evidence for
      two evolutionary hypotheses: sperm competition and sexual conflict.

PMID- 11226271
TI  - Genomic and genetic dissection of an archaeal regulon.
AB  - The extremely halophilic archaeon Halobacterium sp. NRC-1 can grow
      phototrophically by means of light-driven proton pumping by bacteriorhodopsin in
      the purple membrane. Here, we show by genetic analysis of the wild type, and
      insertion and double-frame shift mutants of Bat that this transcriptional
      regulator coordinates synthesis of a structural protein and a chromophore for
      purple membrane biogenesis in response to both light and oxygen. Analysis of the
      complete Halobacterium sp. NRC-1 genome sequence showed that the regulatory site,
      upstream activator sequence (UAS), the putative binding site for Bat upstream of
      the bacterio-opsin gene (bop), is also present upstream to the other Bat
      regulated genes. The transcription regulator Bat contains a photoresponsive cGMP
      binding (GAF) domain, and a bacterial AraC type helix-turn-helix DNA binding
      motif. We also provide evidence for involvement of the PAS/PAC domain of Bat in
      redox-sensing activity by genetic analysis of a purple membrane overproducer.
      Five additional Bat-like putative regulatory genes were found, which together are
      likely to be responsible for orchestrating the complex response of this archaeon
      to light and oxygen. Similarities of the bop-like UAS and transcription factors
      in diverse organisms, including a plant and a gamma-proteobacterium, suggest an
      ancient origin for this regulon capable of coordinating light and oxygen
      responses in the three major branches of the evolutionary tree of life. Finally,
      sensitivity of four of five regulon genes to DNA supercoiling is demonstrated and
      correlated to presence of alternating purine-pyrimidine sequences (RY boxes) near
      the regulated promoters.

PMID- 11226272
TI  - Targeted disruption of the Kcnq1 gene produces a mouse model of Jervell and Lange
      Nielsen Syndrome.
AB  - KCNQ1 encodes KCNQ1, which belongs to a family of voltage-dependent K(+) ion
      channel proteins. KCNQ1 associates with a regulatory subunit, KCNE1, to produce
      the cardiac repolarizing current, I(Ks). Loss-of-function mutations in the human
      KCNQ1 gene have been linked to Jervell and Lange-Nielsen Syndrome (JLNS), a
      disorder characterized by profound bilateral deafness and a cardiac phenotype. To
      generate a mouse model for JLNS, we created a line of transgenic mice that have a
      targeted disruption in the Kcnq1 gene. Behavioral analysis revealed that the
      Kcnq1(-/-) mice are deaf and exhibit a shaker/waltzer phenotype. Histological
      analysis of the inner ear structures of Kcnq1(-/-) mice revealed gross
      morphological anomalies because of the drastic reduction in the volume of
      endolymph. ECGs recorded from Kcnq1(-/-) mice demonstrated abnormal T- and P-wave
      morphologies and prolongation of the QT and JT intervals when measured in vivo,
      but not in isolated hearts. These changes are indicative of cardiac
      repolarization defects that appear to be induced by extracardiac signals.
      Together, these data suggest that Kcnq1(-/-) mice are a potentially valuable
      animal model of JLNS.

PMID- 11226273
TI  - Somatic mosaicism in Fanconi anemia: evidence of genotypic reversion in
      lymphohematopoietic stem cells.
AB  - Somatic mosaicism has been observed previously in the lymphocyte population of
      patients with Fanconi anemia (FA). To identify the cellular origin of the
      genotypic reversion, we examined each lymphohematopoietic and stromal cell
      lineage in an FA patient with a 2815-2816ins19 mutation in FANCA and known
      lymphocyte somatic mosaicism. DNA extracted from individually plucked peripheral
      blood T cell colonies and marrow colony-forming unit granulocyte-macrophage and
      burst-forming unit erythroid cells revealed absence of the maternal FANCA exon 29
      mutation in 74.0%, 80.3%, and 86.2% of colonies, respectively. These data,
      together with the absence of the FANCA exon 29 mutation in Epstein-Barr virus
      transformed B cells and its presence in fibroblasts, indicate that genotypic
      reversion, most likely because of back mutation, originated in a
      lymphohematopoietic stem cell and not solely in a lymphocyte population. Contrary
      to a predicted increase in marrow cellularity resulting from reversion in a
      hematopoietic stem cell, pancytopenia was progressive. Additional evaluations
      revealed a partial deletion of 11q in 3 of 20 bone marrow metaphase cells. By
      using interphase fluorescence in situ hybridization with an MLL gene probe mapped
      to band 11q23 to identify colony-forming unit granulocyte-macrophage and burst
      forming unit erythroid cells with the 11q deletion, the abnormal clone was
      exclusive to colonies with the FANCA exon 29 mutation. Thus, we demonstrate the
      spontaneous genotypic reversion in a lymphohematopoietic stem cell. The
      subsequent development of a clonal cytogenetic abnormality in nonrevertant cells
      suggests that ex vivo correction of hematopoietic stem cells by gene transfer may
      not be sufficient for providing life-long stable hematopoiesis in patients with
      FA.

PMID- 11226274
TI  - Spectral karyotyping suggests additional subsets of colorectal cancers
      characterized by pattern of chromosome rearrangement.
AB  - The abundant chromosome abnormalities in most carcinomas are probably a
      reflection of genomic instability present in the tumor, so the pattern and
      variability of chromosome abnormalities will reflect the mechanism of instability
      combined with the effects of selection. Chromosome rearrangement was investigated
      in 17 colorectal carcinoma-derived cell lines. Comparative genomic hybridization
      showed that the chromosome changes were representative of those found in primary
      tumors. Spectral karyotyping (SKY) showed that translocations were very varied
      and mostly unbalanced, with no translocation occurring in more than three lines.
      At least three karyotype patterns could be distinguished. Some lines had few
      chromosome abnormalities: they all showed microsatellite instability, the
      replication error (RER)+ phenotype. Most lines had many chromosome abnormalities:
      at least seven showed a surprisingly consistent pattern, characterized by
      multiple unbalanced translocations and intermetaphase variation, with chromosome
      numbers around triploid, 6-16 structural aberrations, and similarities in gains
      and losses. Almost all of these were RER-, but one, LS411, was RER+. The line
      HCA7 showed a novel pattern, suggesting a third kind of genomic instability:
      multiple reciprocal translocations, with little numerical change or variability.
      This line was also RER+. The coexistence in one tumor of two kinds of genomic
      instability is to be expected if the underlying defects are selected for in tumor
      evolution.

PMID- 11226275
TI  - Establishment of medaka (Oryzias latipes) transgenic lines with the expression of
      green fluorescent protein fluorescence exclusively in germ cells: a useful model
      to monitor germ cells in a live vertebrate.
AB  - We have generated transgenic medaka (teleost, Oryzias latipes), which allow us to
      monitor germ cells by green fluorescent protein (GFP) fluorescence in live
      specimens. Two medaka strains, himedaka (orange-red variety) and inbred QurtE,
      were used. The transgenic lines were achieved by microinjection of a construct
      containing the putative promoter region and 3' region of the medaka vasa gene
      (olvas). The intensity of GFP fluorescence increases dramatically in primordial
      germ cells (PGCs) located in the ventrolateral region of the posterior intestine
      around stage 25 (the onset of blood circulation). Whole-mount in situ
      hybridization and monitoring of ectopically located cells by GFP fluorescence
      suggested that (i) the increase in zygotic olvas expression occurs after PGC
      specification and (ii) PGCs can maintain their cell characteristics ectopically
      after stages 20-25. Around the day of hatching, the QurtE strain clearly exhibits
      sexual dimorphisms in the number of GFP fluorescent germ cells, a finding
      consistent with the appearance of leucophores, a sex-specific marker of QurtE.
      The GFP expression persists throughout the later stages in the mature ovary and
      testis. Thus, these transgenic medaka represent a live vertebrate model to
      investigate how germ cells migrate to form sexually dimorphic gonads, as well as
      a potential assay system for environmental substances that may affect gonad
      development. The use of a transgenic construct as a selective marker to
      efficiently isolate germ-line-transmitting founders during embryogenesis is also
      discussed.

PMID- 11226277
TI  - A genomic approach to gene fusion technology.
AB  - Gene expression profiling provides powerful analyses of transcriptional responses
      to cellular perturbation. In contrast to DNA array-based methods, reporter gene
      technology has been underused for this application. Here we describe a
      genomewide, genome-registered collection of Escherichia coli bioluminescent
      reporter gene fusions. DNA sequences from plasmid-borne, random fusions of E.
      coli chromosomal DNA to a Photorhabdus luminescens luxCDABE reporter allowed
      precise mapping of each fusion. The utility of this collection covering about 30%
      of the transcriptional units was tested by analyzing individual fusions
      representative of heat shock, SOS, OxyR, SoxRS, and cya/crp stress-responsive
      regulons. Each fusion strain responded as anticipated to environmental conditions
      known to activate the corresponding regulatory circuit. Thus, the collection
      mirrors E. coli's transcriptional wiring diagram. This genomewide collection of
      gene fusions provides an independent test of results from other gene expression
      analyses. Accordingly, a DNA microarray-based analysis of mitomycin C-treated E.
      coli indicated elevated expression of expected and unanticipated genes. Selected
      luxCDABE fusions corresponding to these up-regulated genes were used to confirm
      or contradict the DNA microarray results. The power of partnering gene fusion and
      DNA microarray technology to discover promoters and define operons was
      demonstrated when data from both suggested that a cluster of 20 genes encoding
      production of type I extracellular polysaccharide in E. coli form a single
      operon.

PMID- 11226276
TI  - Interaction of a transcriptional repressor with the RNA polymerase II holoenzyme
      plays a crucial role in repression.
AB  - The yeast transcriptional repressor Tup1, tethered to DNA, represses to
      strikingly different degrees transcription elicited by members of two classes of
      activators. Repression in both cases is virtually eliminated by mutation of
      either member of the cyclin-kinase pair Srb10/11. In contrast, telomeric
      chromatin affects both classes of activators equally, and in neither case is that
      repression affected by mutation of Srb10/11. In vitro, Tup1 interacts with RNA
      polymerase II holoenzyme bearing Srb10 as well as with the separated Srb10. These
      and other findings indicate that at least one aspect of Tup1's action involves
      interaction with the RNA polymerase II holoenzyme.

PMID- 11226278
TI  - Defective localization of the NADPH phagocyte oxidase to Salmonella-containing
      phagosomes in tumor necrosis factor p55 receptor-deficient macrophages.
AB  - Tumor necrosis factor receptor (TNFR) p55-knockout (KO) mice are susceptible
      profoundly to Salmonella infection. One day after peritoneal inoculation, TNFR-KO
      mice harbor 1,000-fold more bacteria in liver and spleen than wild-type mice
      despite the formation of well organized granulomas. Macrophages from TNFR-KO mice
      produce abundant quantities of reactive oxygen and nitrogen species in response
      to Salmonella but nevertheless exhibit poor bactericidal activity. Treatment with
      IFN-gamma enhances killing by wild-type macrophages but does not restore the
      killing defect of TNFR-KO cells. Bactericidal activity of macrophages can be
      abrogated by a deletion in the gene encoding TNFalpha but not by saturating
      concentrations of TNF-soluble receptor, suggesting that intracellular TNFalpha
      can regulate killing of Salmonella by macrophages. Peritoneal macrophages from
      TNFR-KO mice fail to localize NADPH oxidase-containing vesicles to Salmonella
      containing vacuoles. A TNFR-KO mutation substantially restores virulence to an
      attenuated mutant bacterial strain lacking the type III secretory system encoded
      by Salmonella pathogenicity island 2 (SPI2), suggesting that TNFalpha and SPI2
      have opposing actions on a common pathway of vesicular trafficking. TNFalpha
      TNFRp55 signaling plays a critical role in the immediate innate immune response
      to an intracellular pathogen by optimizing the delivery of toxic reactive oxygen
      species to the phagosome.

PMID- 11226279
TI  - Impaired survival of T helper cells in the absence of CD4.
AB  - Signal transduction in response to ligand recognition by T cell receptors
      regulates T cell fate within and beyond the thymus. Herein we examine the
      involvement of the CD4 molecule in the regulation of T helper cell survival. T
      helper cells that lack CD4 expression are prone to apoptosis and show diminished
      survival after adoptive transfer to irradiated recipients. The helper lineage in
      CD4(-/-) animals shows a higher than normal apparent rate of cell division and is
      also enriched for cells exhibiting a memory cell phenotype. Thus the data point
      to a necessary role for CD4 in the regulation of T helper cell survival and
      homeostasis.

PMID- 11226280
TI  - Spontaneous retinopathy in HLA-A29 transgenic mice.
AB  - Humans who have inherited the class I major histocompatibility allele HLA-A29
      have a markedly increased relative risk of developing the eye disease termed
      birdshot chorioretinopathy. This disease affecting adults is characterized by
      symmetrically scattered, small, cream-colored spots in the fundus associated with
      retinal vasculopathy and inflammatory signs causing damage to the ocular
      structures, leading regularly to visual loss. To investigate the role of HLA-A29
      in this disease, we introduced the HLA-A29 gene into mice. Aging HLA-A29
      transgenic mice spontaneously developed retinopathy, showing a striking
      resemblance to the HLA-A29-associated chorioretinopathy. These results strongly
      suggest that HLA-A29 is involved in the pathogenesis of this disease. Elucidation
      of the role of HLA-A29 should be assisted by this transgenic model.

PMID- 11226282
TI  - BLNK mediates Syk-dependent Btk activation.
AB  - Btk is a critical molecule in B cell antigen receptor (BCR)-coupled signaling,
      and its activity is regulated by Lyn and Syk. Although the molecular mechanism of
      Lyn-dependent Btk activation has been investigated, that of Syk-dependent Btk
      activation has remained unidentified. We have demonstrated that BLNK mediates Syk
      dependent Btk activation. In a reconstitution cell system, coexpression of BLNK
      allows Syk to phosphorylate Btk on its tyrosine 551, leading to the enhancement
      of Btk activity. This phosphorylation depends on the interaction of Btk and BLNK
      by means of the Btk-Src homology 2 domain. The existence of such an activation
      mechanism is supported by the observation that the BCR-induced Btk
      phosphorylation and activation are significantly reduced in BLNK-deficient B
      cells as well as in Syk-deficient B cells. Although previous observations have
      identified the function of BLNK as the linker that integrates the action of Btk
      and Syk into downstream effectors such as phospholipase Cgamma2, our present
      study indicates another function of BLNK that connects the activity of Syk to
      that of Btk.

PMID- 11226281
TI  - Requirement for natural killer T (NKT) cells in the induction of allograft
      tolerance.
AB  - In this study, we investigated the role of Valpha14 natural killer T (NKT) cells
      in transplant immunity. The ability to reject allografts was not significantly
      different between wild-type (WT) and Valpha14 NKT cell-deficient mice. However,
      in models in which tolerance was induced against cardiac allografts by blockade
      of lymphocyte function-associated antigen-1/intercellular adhesion molecule-1 or
      CD28/B7 interactions, long-term acceptance of the grafts was observed only in WT
      but not Valpha14 NKT cell-deficient mice. Adoptive transfer with Valpha14 NKT
      cells restored long-term acceptance of allografts in Valpha14 NKT cell-deficient
      mice. The critical role of Valpha14 NKT cells to mediate immunosuppression was
      also observed in vitro in mixed lymphocyte cultures in which lymphocyte function
      associated antigen-1/intercellular adhesion molecule-1 or CD28/B7 interactions
      were blocked. Experiments using IL-4- or IFN-gamma-deficient mice suggested a
      critical contribution of IFN-gamma to the Valpha14 NKT cell-mediated allograft
      acceptance in vivo. These results indicate a critical contribution of Valpha14
      NKT cells to the induction of allograft tolerance and provide a useful model to
      investigate the regulatory role of Valpha14 NKT cells in various immune
      responses.

PMID- 11226283
TI  - Lack of a role for transforming growth factor-beta in cytotoxic T lymphocyte
      antigen-4-mediated inhibition of T cell activation.
AB  - Similarities in the phenotypes of mice deficient for cytotoxic T lymphocyte
      antigen-4 (CTLA-4) or transforming growth factor-beta1 (TGF-beta1) and other
      observations have led to speculation that CTLA-4 mediates its inhibitory effect
      on T cell activation via costimulation of TGF-beta production. Here, we examine
      the role of TGF-beta in CTLA-4-mediated inhibition of T cell activation and of
      CTLA-4 in the regulation of TGF-beta production. Activation of AND TCR transgenic
      mouse T cells with costimulatory receptor-specific antigen presenting cells
      results in efficient costimulation of proliferation by CD28 ligation and
      inhibition by CTLA-4 ligation. Neutralizing antibody to TGF-beta does not reverse
      CTLA-4-mediated inhibition. Also, CTLA-4 ligation equally inhibits proliferation
      of wild-type, TGF-beta1(-/-), and Smad3(-/-) T cells. Further, CTLA-4 engagement
      does not result in the increased production of either latent or active TGF-beta
      by CD4(+) T cells. These results indicate that CTLA-4 ligation does not regulate
      TGF-beta production and that CTLA-4-mediated inhibition can occur independently
      of TGF-beta. Collectively, these data demonstrate that CTLA-4 and TGF-beta
      represent distinct mechanisms for regulation of T cell responses.

PMID- 11226284
TI  - Prevention of ischemia-induced retinopathy by the natural ocular antiangiogenic
      agent pigment epithelium-derived factor.
AB  - Aberrant blood vessel growth in the retina that underlies the pathology of
      proliferative diabetic retinopathy and retinopathy of prematurity is the result
      of the ischemia-driven disruption of the normally antiangiogenic environment of
      the retina. In this study, we show that a potent inhibitor of angiogenesis found
      naturally in the normal eye, pigment epithelium-derived growth factor (PEDF),
      inhibits such aberrant blood vessel growth in a murine model of ischemia-induced
      retinopathy. Inhibition was proportional to dose and systemic delivery of
      recombinant protein at daily doses as low as 2.2 mg/kg could prevent aberrant
      endothelial cells from crossing the inner limiting membrane. PEDF appeared to
      inhibit angiogenesis by causing apoptosis of activated endothelial cells, because
      it induced apoptosis in cultured endothelial cells and an 8-fold increase in
      apoptotic endothelial cells could be detected in situ when the ischemic retinas
      of PEDF-treated animals were compared with vehicle-treated controls. The ability
      of low doses of PEDF to curtail aberrant growth of ocular endothelial cells
      without overt harm to retinal morphology suggests that this natural protein may
      be beneficial in the treatment of a variety of retinal vasculopathies.

PMID- 11226285
TI  - Genetic disruption of PPARdelta decreases the tumorigenicity of human colon
      cancer cells.
AB  - Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors
      that have been implicated in a variety of biologic processes. The PPARdelta
      isotype was recently proposed as a downstream target of the adenomatous polyposis
      coli (APC)/beta-catenin pathway in colorectal carcinogenesis. To evaluate its
      role in tumorigenesis, a PPARdelta null cell line was created by targeted
      homologous recombination. When inoculated as xenografts in nude mice, PPARdelta 
      /- cells exhibited a decreased ability to form tumors compared with PPARdelta +/-
      and wild-type controls. These data suggest that suppression of PPARdelta
      expression contributes to the growth-inhibitory effects of the APC tumor
      suppressor.

PMID- 11226286
TI  - Predominant role of endothelial nitric oxide synthase in vascular endothelial
      growth factor-induced angiogenesis and vascular permeability.
AB  - Nitric oxide (NO) plays a critical role in vascular endothelial growth factor
      (VEGF)-induced angiogenesis and vascular hyperpermeability. However, the relative
      contribution of different NO synthase (NOS) isoforms to these processes is not
      known. Here, we evaluated the relative contributions of endothelial and inducible
      NOS (eNOS and iNOS, respectively) to angiogenesis and permeability of VEGF
      induced angiogenic vessels. The contribution of eNOS was assessed by using an
      eNOS-deficient mouse, and iNOS contribution was assessed by using a selective
      inhibitor [l-N(6)-(1-iminoethyl) lysine, l-NIL] and an iNOS-deficient mouse.
      Angiogenesis was induced by VEGF in type I collagen gels placed in the mouse
      cranial window. Angiogenesis, vessel diameter, blood flow rate, and vascular
      permeability were proportional to NO levels measured with microelectrodes: Wild
      type (WT) > or = WT with l-NIL or iNOS(-/-) > eNOS(-/-) > or = eNOS(-/-) with l
      NIL. The role of NOS in VEGF-induced acute vascular permeability increase in
      quiescent vessels also was determined by using eNOS- and iNOS-deficient mice.
      VEGF superfusion significantly increased permeability in both WT and iNOS(-/-)
      mice but not in eNOS(-/-) mice. These findings suggest that eNOS plays a
      predominant role in VEGF-induced angiogenesis and vascular permeability. Thus,
      selective modulation of eNOS activity is a promising strategy for altering
      angiogenesis and vascular permeability in vivo.

PMID- 11226287
TI  - Reduction of atherosclerosis in apolipoprotein E knockout mice by activation of
      the retinoid X receptor.
AB  - A common feature of many metabolic pathways is their control by retinoid X
      receptor (RXR) heterodimers. Dysregulation of such metabolic pathways can lead to
      the development of atherosclerosis, a disease influenced by both systemic and
      local factors. Here we analyzed the effects of activation of RXR and some of its
      heterodimers in apolipoprotein E -/- mice, a well established animal model of
      atherosclerosis. An RXR agonist drastically reduced the development of
      atherosclerosis. In addition, a ligand for the peroxisome proliferator-activated
      receptor (PPAR)gamma and a dual agonist of both PPARalpha and PPARgamma had
      moderate inhibitory effects. Both RXR and liver X receptor (LXR) agonists induced
      ATP-binding cassette protein 1 (ABC-1) expression and stimulated ABC-1-mediated
      cholesterol efflux from macrophages from wild-type, but not from LXRalpha and
      beta double -/-, mice. Hence, activation of ABC-1-mediated cholesterol efflux by
      the RXR/LXR heterodimer might contribute to the beneficial effects of rexinoids
      on atherosclerosis and warrant further evaluation of RXR/LXR agonists in
      prevention and treatment of atherosclerosis.

PMID- 11226288
TI  - Whole-body and intravital optical imaging of angiogenesis in orthotopically
      implanted tumors.
AB  - The development of drugs for the control of tumor angiogenesis requires a simple,
      accurate, and economical assay for tumor-induced vascularization. We have adapted
      the orthotopic implantation model to angiogenesis measurement by using human
      tumors labeled with Aequorea victoria green fluorescent protein for grafting into
      nude mice. The nonluminous induced capillaries are clearly visible against the
      very bright tumor fluorescence examined either intravitally or by whole-body
      luminance in real time. The orthotopic implantation model of human cancer has
      been well characterized, and fluorescence shadowing replaces the laborious
      histological techniques for determining blood vessel density. Intravital images
      of orthotopically implanted human pancreatic tumors clearly show angiogenic
      capillaries at both primary and metastatic sites. A quantitative time course of
      angiogenesis was determined for an orthotopically growing human prostate tumor
      periodically imaged intravitally in a single nude mouse over a 19-day period.
      Whole-body optical imaging of tumor angiogenesis was demonstrated by injecting
      fluorescent Lewis lung carcinoma cells into the s.c. site of the footpad of nude
      mice. The footpad is relatively transparent, with comparatively few resident
      blood vessels, allowing quantitative imaging of tumor angiogenesis in the intact
      animal. Capillary density increased linearly over a 10-day period as determined
      by whole-body imaging. Similarly, the green fluorescent protein-expressing human
      breast tumor MDA-MB-435 was orthotopically transplanted to the mouse fat pad,
      where whole-body optical imaging showed that blood vessel density increased
      linearly over a 20-week period. These powerful and clinically relevant
      angiogenesis mouse models can be used for real-time in vivo evaluation of agents
      inhibiting or promoting tumor angiogenesis in physiological microenvironments.

PMID- 11226289
TI  - NO chemical events in the human airway during the immediate and late antigen
      induced asthmatic response.
AB  - A wealth of evidence supports increased NO (NO.) in asthma, but its roles are
      unknown. To investigate how NO participates in inflammatory airway events in
      asthma, we measured NO. and NO. chemical reaction products [nitrite, nitrate, S
      nitrosothiols (SNO), and nitrotyrosine] before, immediately and 48 h after
      bronchoscopic antigen (Ag) challenge of the peripheral airways in atopic
      asthmatic individuals and nonatopic healthy controls. Strikingly, NO(3)(-) was
      the only NO. derivative to increase during the immediate Ag-induced asthmatic
      response and continued to increase over 2-fold at 48 h after Ag challenge in
      contrast to controls [P < 0.05]. NO(2)(-) was not affected by Ag challenge at 10
      min or 48 h after Ag challenge. Although SNO was not detectable in asthmatic
      airways at baseline or immediately after Ag, SNO increased during the late
      response to levels found in healthy controls. A model of NO. dynamics derived
      from the current findings predicts that NO. may have harmful effects through
      formation of peroxynitrite, but also subserves an antioxidant role by consuming
      reactive oxygen species during the immediate asthmatic response, whereas
      nitrosylation during the late asthmatic response generates SNO, safe reservoirs
      for removal of toxic NO. derivatives.

PMID- 11226290
TI  - Trichostatin A reverses skewed expression of CD154, interleukin-10, and
      interferon-gamma gene and protein expression in lupus T cells.
AB  - In systemic lupus erythematosus (SLE), T helper cells exhibit increased and
      prolonged expression of cell-surface CD40 ligand (CD154), spontaneously
      overproduce interleukin-10 (IL-10), but underproduce interferon-gamma (IFN
      gamma). We tested the hypothesis that the imbalance of these gene products
      reflects skewed expression of CD154, IL-10, and IFN-gamma genes. Here, we
      demonstrate that the histone deacetylase inhibitor, trichostatin A, significantly
      down-regulated CD154 and IL-10 and up-regulated IFN-gamma gene expression in SLE
      T cells. This reversal corrected the aberrant expression of these gene products,
      thereby enhancing IFN-gamma production and inhibiting IL-10 and CD154 expression.
      That trichostatin A can simultaneously reverse the skewed expression of multiple
      genes implicated in the immunopathogenesis of SLE suggests that this
      pharmacologic agent may be a candidate for the treatment of this autoimmune
      disease.

PMID- 11226291
TI  - Cardiovascular abnormalities with normal blood pressure in tissue kallikrein
      deficient mice.
AB  - Tissue kallikrein is a serine protease thought to be involved in the generation
      of bioactive peptide kinins in many organs like the kidneys, colon, salivary
      glands, pancreas, and blood vessels. Low renal synthesis and urinary excretion of
      tissue kallikrein have been repeatedly linked to hypertension in animals and
      humans, but the exact role of the protease in cardiovascular function has not
      been established largely because of the lack of specific inhibitors. This study
      demonstrates that mice lacking tissue kallikrein are unable to generate
      significant levels of kinins in most tissues and develop cardiovascular
      abnormalities early in adulthood despite normal blood pressure. The heart
      exhibits septum and posterior wall thinning and a tendency to dilatation
      resulting in reduced left ventricular mass. Cardiac function estimated in vivo
      and in vitro is decreased both under basal conditions and in response to beta
      adrenergic stimulation. Furthermore, flow-induced vasodilatation is impaired in
      isolated perfused carotid arteries, which express, like the heart, low levels of
      the protease. These data show that tissue kallikrein is the main kinin-generating
      enzyme in vivo and that a functional kallikrein-kinin system is necessary for
      normal cardiac and arterial function in the mouse. They suggest that the
      kallikrein-kinin system could be involved in the development or progression of
      cardiovascular diseases.

PMID- 11226292
TI  - Top-down morphogenesis of colorectal tumors.
AB  - One of the fundamental tenets of oncology is that tumors arise from stem cells.
      In the colon, stem cells are thought to reside at the base of crypts. In the
      early stages of tumorigenesis, however, dysplastic cells are routinely found at
      the luminal surface of the crypts whereas the cells at the bases of these same
      crypts appear morphologically normal. To understand this discrepancy, we
      evaluated the molecular characteristics of cells isolated from the bases and
      orifices of the same crypts in small colorectal adenomas. We found that the
      dysplastic cells at the tops of the crypts often exhibited genetic alterations of
      adenomatous polyposis coli (APC) and neoplasia-associated patterns of gene
      expression. In contrast, cells located at the base of these same crypts did not
      contain such alterations and were not clonally related to the contiguous
      transformed cells above them. These results imply that development of adenomatous
      polyps proceeds through a top-down mechanism. Genetically altered cells in the
      superficial portions of the mucosae spread laterally and downward to form new
      crypts that first connect to preexisting normal crypts and eventually replace
      them.

PMID- 11226293
TI  - High-sensitivity array analysis of gene expression for the early detection of
      disseminated breast tumor cells in peripheral blood.
AB  - Early detection is an effective means of reducing cancer mortality. Here, we
      describe a highly sensitive high-throughput screen that can identify panels of
      markers for the early detection of solid tumor cells disseminated in peripheral
      blood. The method is a two-step combination of differential display and high
      sensitivity cDNA arrays. In a primary screen, differential display identified 170
      candidate marker genes differentially expressed between breast tumor cells and
      normal breast epithelial cells. In a secondary screen, high-sensitivity arrays
      assessed expression levels of these genes in 48 blood samples, 22 from healthy
      volunteers and 26 from breast cancer patients. Cluster analysis identified a
      group of 12 genes that were elevated in the blood of cancer patients. Permutation
      analysis of individual genes defined five core genes (P < or = 0.05, permax
      test). As a group, the 12 genes generally distinguished accurately between
      healthy volunteers and patients with breast cancer. Mean expression levels of the
      12 genes were elevated in 77% (10 of 13) untreated invasive cancer patients,
      whereas cluster analysis correctly classified volunteers and patients (P =
      0.0022, Fisher's exact test). Quantitative real-time PCR confirmed array results
      and indicated that the sensitivity of the assay (1:2 x 10(8) transcripts) was
      sufficient to detect disseminated solid tumor cells in blood. Expression-based
      blood assays developed with the screening approach described here have the
      potential to detect and classify solid tumor cells originating from virtually any
      primary site in the body.

PMID- 11226294
TI  - An NO derivative of ursodeoxycholic acid protects against Fas-mediated liver
      injury by inhibiting caspase activity.
AB  - Caspases are key mediators in liver inflammation and apoptosis. In the present
      study we provide evidence that a nitric oxide (NO) derivative of ursodeoxycholic
      acid (UDCA), NCX-1000 ([2-(acetyloxy)benzoic acid 3-(nitrooxymethyl)phenyl
      ester]), protects against liver damage in murine models of autoimmune hepatitis
      induced by i.v. injection of Con A or a Fas agonistic antibody, Jo2. Con A
      administration causes CD4(+) T lymphocytes to accumulate in the liver and up
      regulates FasL expression, resulting in FasL-mediated cytotoxicity. Cotreating
      mice with NCX-1000, but not with UDCA, protected against liver damage induced by
      Con A and Jo2, inhibited IL-1beta, IL-18, and IFN-gamma release and caspase 3, 8,
      and 9 activation. Studies on HepG2 cells demonstrated that NCX-1000, but not
      UDCA, directly prevented multiple caspase activation induced by Jo2. Incubating
      HepG2 cells with NCX-1000 resulted in intracellular NO formation and a DTT
      reversible inhibition of proapoptotic caspases, suggesting that cysteine S
      nitrosylation was the main mechanism responsible for caspase inhibition.
      Collectively, these data suggest that NCX-1000 protects against T helper 1
      mediated liver injury by inhibiting both the proapoptotic and the proinflammatory
      branches of the caspase superfamily.

PMID- 11226295
TI  - Anti-PSCA mAbs inhibit tumor growth and metastasis formation and prolong the
      survival of mice bearing human prostate cancer xenografts.
AB  - Prostate stem-cell antigen (PSCA) is a cell-surface antigen expressed in normal
      prostate and overexpressed in prostate cancer tissues. PSCA expression is
      detected in over 80% of patients with local disease, and elevated levels of PSCA
      are correlated with increased tumor stage, grade, and androgen independence,
      including high expression in bone metastases. We evaluated the therapeutic
      efficacy of anti-PSCA mAbs in human prostate cancer xenograft mouse models by
      using the androgen-dependent LAPC-9 xenograft and the androgen-independent
      recombinant cell line PC3-PSCA. Two different anti-PSCA mAbs, 1G8 (IgG1kappa) and
      3C5 (IgG2akappa), inhibited formation of s.c. and orthotopic xenograft tumors in
      a dose-dependent manner. Furthermore, administration of anti-PSCA mAbs led to
      retardation of established orthotopic tumor growth and inhibition of metastasis
      to distant sites, resulting in a significant prolongation in the survival of
      tumor-bearing mice. These studies suggest PSCA as an attractive target for
      immunotherapy and demonstrate the therapeutic potential of anti-PSCA mAbs for the
      treatment of local and metastatic prostate cancer.

PMID- 11226296
TI  - The surface variant antigens of Plasmodium falciparum contain cross-reactive
      epitopes.
AB  - Plasmodium falciparum parasites evade the host immune system by clonal expression
      of the variant antigen, P. falciparum erythrocyte membrane protein 1 (PfEMP1).
      Antibodies to PfEMP1 correlate with development of clinical immunity but are
      predominantly variant-specific. To overcome this major limitation for vaccine
      development, we set out to identify cross-reactive epitopes on the surface of
      parasitized erythrocytes (PEs). We prepared mAbs to the cysteine-rich interdomain
      region 1 (CIDR1) of PfEMP1 that is functionally conserved for binding to CD36.
      Two mAbs, targeting different regions of CIDR1, reacted with multiple P.
      falciparum strains expressing variant PfEMP1s. One of these mAbs, mAb 6A2-B1,
      recognized nine of 10 strains tested, failing to react with only one strain that
      does not bind CD36. Flow cytometry with Chinese hamster ovary cells expressing
      variant CIDR1s demonstrated that both mAbs recognized the CIDR1 of various CD36
      binding PfEMP1s and are truly cross-reactive. The demonstration of cross-reactive
      epitopes on the PE surface provides further credence for development of effective
      vaccines against the variant antigen on the surface of P. falciparum-infected
      erythrocytes.

PMID- 11226298
TI  - Adeno-associated viral vector-mediated gene transfer results in long-term
      enzymatic and functional correction in multiple organs of Fabry mice.
AB  - Fabry disease is a lysosomal storage disorder caused by a deficiency of the
      lysosomal enzyme alpha-galactosidase A (alpha-gal A). This enzyme deficiency
      leads to impaired catabolism of alpha-galactosyl-terminal lipids such as
      globotriaosylceramide (Gb3). Patients develop painful neuropathy and vascular
      occlusions that progressively lead to cardiovascular, cerebrovascular, and renal
      dysfunction and early death. Although enzyme replacement therapy and bone marrow
      transplantation have shown promise in the murine analog of Fabry disease, gene
      therapy holds a strong potential for treating this disease in humans. Delivery of
      the normal alpha-gal A gene (cDNA) into a depot organ such as liver may be
      sufficient to elicit corrective circulating levels of the deficient enzyme. To
      investigate this possibility, a recombinant adeno-associated viral vector
      encoding human alpha-gal A (rAAV-AGA) was constructed and injected into the
      hepatic portal vein of Fabry mice. Two weeks postinjection, alpha-gal A activity
      in the livers of rAAV-AGA-injected Fabry mice was 20-35% of that of the normal
      mice. The transduced animals continued to show higher alpha-gal A levels in liver
      and other tissues compared with the untouched Fabry controls as long as 6 months
      after treatment. In parallel to the elevated enzyme levels, we see significant
      reductions in Gb3 levels to near normal at 2 and 5 weeks posttreatment. The lower
      Gb3 levels continued in liver, spleen, and heart, up to 25 weeks with no
      significant immune response to the virus or alpha-gal A. Also, no signs of liver
      toxicity occurred after the rAAV-AGA administration. These findings suggest that
      an AAV-mediated gene transfer may be useful for the treatment of Fabry disease
      and possibly other metabolic disorders.

PMID- 11226297
TI  - DC-SIGNR, a DC-SIGN homologue expressed in endothelial cells, binds to human and
      simian immunodeficiency viruses and activates infection in trans.
AB  - DC-SIGN, a C-type lectin expressed on the surface of dendritic cells (DCs),
      efficiently binds and transmits HIVs and simian immunodeficiency viruses to
      susceptible cells in trans. A DC-SIGN homologue, termed DC-SIGNR, has recently
      been described. Herein we show that DC-SIGNR, like DC-SIGN, can bind to multiple
      strains of HIV-1, HIV-2, and simian immunodeficiency virus and transmit these
      viruses to both T cell lines and human peripheral blood mononuclear cells.
      Binding of virus to DC-SIGNR was dependent on carbohydrate recognition.
      Immunostaining with a DC-SIGNR-specific antiserum showed that DC-SIGNR was
      expressed on sinusoidal endothelial cells in the liver and on endothelial cells
      in lymph node sinuses and placental villi. The presence of this efficient virus
      attachment factor on multiple endothelial cell types indicates that DC-SIGNR
      could play a role in the vertical transmission of primate lentiviruses, in the
      enabling of HIV to traverse the capillary endothelium in some organs, and in the
      presentation of virus to CD4-positive cells in multiple locations including lymph
      nodes.

PMID- 11226299
TI  - Antibodies to human fetal erythroid cells from a nonimmune phage antibody
      library.
AB  - The ability to isolate fetal nucleated red blood cells (NRBCs) from the maternal
      circulation makes possible prenatal genetic analysis without the need for
      diagnostic procedures that are invasive for the fetus. Such isolation requires
      antibodies specific to fetal NRBCs. To generate a panel of antibodies to antigens
      present on fetal NRBCs, a new type of nonimmune phage antibody library was
      generated in which multiple copies of antibody fragments are displayed on each
      phage. Antibody fragments specific for fetal NRBCs were isolated by extensive
      predepletion of the phage library on adult RBCs and white blood cells (WBCs)
      followed by positive selection and amplification on fetal liver erythroid cells.
      After two rounds of selection, 44% of the antibodies analyzed bound fetal NRBCs,
      with two-thirds of these showing no binding of WBCs. DNA fingerprint analysis
      revealed the presence of at least 16 unique antibodies. Antibody specificity was
      confirmed by flow cytometry, immunohistochemistry, and immunofluorescence of
      total fetal liver and adult RBCs and WBCs. Antibody profiling suggested the
      generation of antibodies to previously unknown fetal RBC antigens. We conclude
      that multivalent display of antibodies on phage leads to efficient selection of
      panels of specific antibodies to cell surface antigens. The antibodies generated
      to fetal RBC antigens may have clinical utility for isolating fetal NRBCs from
      maternal circulation for noninvasive prenatal genetic diagnosis. Some of the
      antibodies may also have possible therapeutic utility for erythroleukemia.

PMID- 11226300
TI  - Chronic elevation of plasma thioredoxin: inhibition of chemotaxis and curtailment
      of life expectancy in AIDS.
AB  - Thioredoxin (Trx) is an intracellular redox protein with extracellular cytokine
      like and chemokine-like activities. We show here that, although plasma Trx levels
      are unrelated to survival of HIV-infected individuals with CD4 cell counts above
      200/microl blood, survival is significantly impaired (P = 0.003) when plasma Trx
      is chronically elevated in HIV-infected subjects with CD4 T cell counts below
      this level (i.e., with Centers for Disease Control (CDC)-defined AIDS). Relevant
      to the mechanism potentially underlying this finding, we also present data from
      experimental studies in mice showing that elevated plasma Trx efficiently blocks
      lipopolysaccharide (LPS)-induced chemotaxis, an innate immune mechanism that is
      particularly crucial when adaptive immunity is compromised. Thus, we propose that
      elevated plasma Trx in HIV-infected individuals with low CD4 T cell counts
      directly impairs survival by blocking pathogen-induced chemotaxis, effectively
      eliminating the last (innate) barrier against establishment of opportunistic and
      other infections in these immunodeficient individuals.

PMID- 11226301
TI  - Alkaline-mediated differential interaction (AMDI): a simple automatable single
      nucleotide polymorphism assay.
AB  - The key requirements for high-throughput single-nucleotide polymorphism (SNP)
      typing of DNA samples in large-scale disease case-control studies are
      automatability, simplicity, and robustness, coupled with minimal cost. In this
      paper we describe a fluorescence technique for the detection of SNPs that have
      been amplified by using the amplification refractory mutation system (ARMS)-PCR
      procedure. Its performance was evaluated using 32 sequence-specific primer mixes
      to assign the HLA-DRB alleles to 80 lymphoblastoid cell line DNAs chosen from our
      database for their diversity. All had been typed previously by alternative
      methods, either direct sequencing or gel electrophoresis. We believe the
      detection system that we call AMDI (alkaline-mediated differential interaction)
      satisfies the above criteria and is suitable for general high-throughput SNP
      typing.

PMID- 11226303
TI  - A genetic model provides evidence that the receptor for atrial natriuretic
      peptide (guanylyl cyclase-A) inhibits cardiac ventricular myocyte hypertrophy.
AB  - Guanylyl cyclase-A (NPR-A; GC-A) is the major and possibly the only receptor for
      atrial natriuretic peptide (ANP) or B-type natriuretic peptide. Although mice
      deficient in GC-A display an elevated blood pressure, the resultant cardiac
      hypertrophy is much greater than in other mouse models of hypertension. Here we
      overproduce GC-A in the cardiac myocytes of wild-type or GC-A null animals.
      Introduction of the GC-A transgene did not alter blood pressure or heart rate as
      a function of genotype. Cardiac myocyte size was larger (approximately 20%) in GC
      A null than in wild-type animals. However, introduction of the GC-A transgene
      reduced cardiac myocyte size in both wild-type and null mice. Coincident with the
      reduction in myocyte size, both ANP mRNA and ANP content were significantly
      reduced by overexpression of GC-A, and this reduction was independent of
      genotype. This genetic model, therefore, separates a regulation of cardiac
      myocyte size by blood pressure from local regulation by a GC-mediated pathway.

PMID- 11226302
TI  - Mechanisms underlying losses of heterozygosity in human colorectal cancers.
AB  - Losses of heterozygosity are the most common molecular genetic alteration
      observed in human cancers. However, there have been few systematic studies to
      understand the mechanism(s) responsible for losses of heterozygosity in such
      tumors. Here we report a detailed investigation of the five chromosomes lost most
      frequently in human colorectal cancers. A total of 10,216 determinations were
      made with 88 microsatellite markers, revealing 245 chromosomal loss events. The
      mechanisms of loss were remarkably chromosome-specific. Some chromosomes
      displayed complete loss such as that predicted to result from mitotic
      nondisjunction. However, more than half of the losses were associated with losses
      of only part of a chromosome rather than a whole chromosome. Surprisingly, these
      losses were due largely to structural alterations rather than to mitotic
      recombination, break-induced replication, or gene conversion, suggesting novel
      mechanisms for the generation of much of the aneuploidy in this common tumor
      type.

PMID- 11226304
TI  - Mouse strain differences determine severity of iron accumulation in Hfe knockout
      model of hereditary hemochromatosis.
AB  - Hereditary hemochromatosis (HH) is a common disorder of iron metabolism caused by
      mutation in HFE, a gene encoding an MHC class I-like protein. Clinical studies
      demonstrate that the severity of iron loading is highly variable among
      individuals with identical HFE genotypes. To determine whether genetic factors
      other than Hfe genotype influence the severity of iron loading in the murine
      model of HH, we bred the disrupted murine Hfe allele onto three different
      genetically defined mouse strains (AKR, C57BL/6, and C3H), which differ in basal
      iron status and sensitivity to dietary iron loading. Serum transferrin
      saturations (percent saturation of serum transferrin with iron), hepatic and
      splenic iron concentrations, and hepatocellular iron distribution patterns were
      compared for wild-type (Hfe +/+), heterozygote (Hfe +/-), and knockout (Hfe -/-)
      mice from each strain. Although the Hfe -/- mice from all three strains
      demonstrated increased transferrin saturations and liver iron concentrations
      compared with Hfe +/+ mice, strain differences in severity of iron accumulation
      were striking. Targeted disruption of the Hfe gene led to hepatic iron levels in
      Hfe -/- AKR mice that were 2.5 or 3.6 times higher than those of Hfe -/- C3H or
      Hfe -/- C57BL/6 mice, respectively. The Hfe -/- mice also demonstrated strain
      dependent differences in transferrin saturation, with the highest values in AKR
      mice and the lowest values in C3H mice. These observations demonstrate that
      heritable factors markedly influence iron homeostasis in response to Hfe
      disruption. Analysis of mice from crosses between C57BL/6 and AKR mice should
      allow the mapping and subsequent identification of genes modifying the severity
      of iron loading in this murine model of HH.

PMID- 11226305
TI  - Transcriptome of a mouse kidney cortical collecting duct cell line: effects of
      aldosterone and vasopressin.
AB  - Aldosterone and vasopressin are responsible for the final adjustment of sodium
      and water reabsorption in the kidney. In principal cells of the kidney cortical
      collecting duct (CCD), the integral response to aldosterone and the long-term
      functional effects of vasopressin depend on transcription. In this study, we
      analyzed the transcriptome of a highly differentiated mouse clonal CCD principal
      cell line (mpkCCD(cl4)) and the changes in the transcriptome induced by
      aldosterone and vasopressin. Serial analysis of gene expression (SAGE) was
      performed on untreated cells and on cells treated with either aldosterone or
      vasopressin for 4 h. The transcriptomes in these three experimental conditions
      were determined by sequencing 169,721 transcript tags from the corresponding SAGE
      libraries. Limiting the analysis to tags that occurred twice or more in the data
      set, 14,654 different transcripts were identified, 3,642 of which do not match
      known mouse sequences. Statistical comparison (at P < 0.05 level) of the three
      SAGE libraries revealed 34 AITs (aldosterone-induced transcripts), 29 ARTs
      (aldosterone-repressed transcripts), 48 VITs (vasopressin-induced transcripts)
      and 11 VRTs (vasopressin-repressed transcripts). A selection of the
      differentially-expressed, hormone-specific transcripts (5 VITs, 2 AITs and 1 ART)
      has been validated in the mpkCCD(cl4) cell line either by Northern blot
      hybridization or reverse transcription-PCR. The hepatocyte nuclear transcription
      factor HNF-3-alpha (VIT39), the receptor activity modifying protein RAMP3
      (VIT48), and the glucocorticoid-induced leucine zipper protein (GILZ) (AIT28) are
      candidate proteins playing a role in physiological responses of this cell line to
      vasopressin and aldosterone.

PMID- 11226306
TI  - Evaluation of the role of heterogeneous nuclear ribonucleoprotein A1 as a host
      factor in murine coronavirus discontinuous transcription and genome replication.
AB  - Viruses with RNA genomes often capture and redirect host cell components to
      assist in mechanisms particular to RNA-dependent RNA synthesis. The nidoviruses
      are an order of positive-stranded RNA viruses, comprising coronaviruses and
      arteriviruses, that employ a unique strategy of discontinuous transcription,
      producing a series of subgenomic mRNAs linking a 5' leader to distal portions of
      the genome. For the prototype coronavirus mouse hepatitis virus (MHV),
      heterogeneous nuclear ribonucleoprotein (hnRNP) A1 has been shown to be able to
      bind in vitro to the negative strand of the intergenic sequence, a cis-acting
      element found in the leader RNA and preceding each downstream ORF in the genome.
      hnRNP A1 thus has been proposed as a host factor in MHV transcription. To test
      this hypothesis genetically, we initially constructed MHV mutants with a very
      high-affinity hnRNP A1 binding site inserted in place of, or adjacent to, an
      intergenic sequence in the MHV genome. This inserted hnRNP A1 binding site was
      not able to functionally replace, or enhance transcription from, the intergenic
      sequence. This finding led us to test more directly the role of hnRNP A1 by
      analysis of MHV replication and RNA synthesis in a murine cell line that does not
      express this protein. The cellular absence of hnRNP A1 had no detectable effect
      on the production of infectious virus, the synthesis of genomic RNA, or the
      quantity or quality of subgenomic mRNAs. These results strongly suggest that
      hnRNP A1 is not a required host factor for MHV discontinuous transcription or
      genome replication.

PMID- 11226308
TI  - Expression of the Anabaena hetR gene from a copper-regulated promoter leads to
      heterocyst differentiation under repressing conditions.
AB  - Heterocyst differentiation in the filamentous cyanobacterium Anabaena PCC 7120
      requires a functional hetR gene. Increased expression of the hetR gene is seen in
      developing and mature heterocysts in response to fixed nitrogen limitation. We
      mapped four likely transcriptional start sites for hetR and identified a specific
      transcript that is positively autoregulated. By using the copper-responsive petE
      promoter from Anabaena PCC 7120 to drive hetR expression, we show that ectopic
      expression of hetR increases heterocyst frequency and induces heterocyst
      differentiation under fully repressing conditions. Coexpression of a reporter
      gene shows that expression from the petE promoter is smoothly induced depending
      on the amount of copper supplied. In the heterocyst pattern mutant PatA, where
      terminally positioned heterocysts are formed almost exclusively, expression of
      the petEhetR fusion does not result in the formation of intercalary heterocysts.
      These results suggest that although the intracellular concentration of HetR has
      to be elevated for the differentiation decision, PatA plays a role as well. This
      role may be in the form of posttranslational modification of HetR, because PatA
      is a member of the response regulator family of proteins.

PMID- 11226307
TI  - Subcellular localization of acetyl-CoA carboxylase in the apicomplexan parasite
      Toxoplasma gondii.
AB  - Apicomplexan parasites such as Toxoplasma gondii contain a primitive plastid, the
      apicoplast, whose genome consists of a 35-kb circular DNA related to the plastid
      DNA of plants. Plants synthesize fatty acids in their plastids. The first
      committed step in fatty acid synthesis is catalyzed by acetyl-CoA carboxylase
      (ACC). This enzyme is encoded in the nucleus, synthesized in the cytosol, and
      transported into the plastid. In the present work, two genes encoding ACC from T.
      gondii were cloned and the gene structure was determined. Both ORFs encode
      multidomain proteins, each with an N-terminal extension, compared with the
      cytosolic ACCs from plants. The N-terminal extension of one isozyme, ACC1, was
      shown to target green fluorescent protein to the apicoplast of T. gondii. In
      addition, the apicoplast contains a biotinylated protein, consistent with the
      assertion that ACC1 is localized there. The second ACC in T. gondii appears to be
      cytosolic. T. gondii mitochondria also contain a biotinylated protein, probably
      pyruvate carboxylase. These results confirm the essential nature of the
      apicoplast and explain the inhibition of parasite growth in cultured cells by
      herbicides targeting ACC.

PMID- 11226309
TI  - Programmed cell death mediated by ced-3 and ced-4 protects Caenorhabditis elegans
      from Salmonella typhimurium-mediated killing.
AB  - Programmed cell death (PCD) in mammals has been implicated in several disease
      states including cancer, autoimmune disease, and neurodegenerative disease. In
      Caenorhabditis elegans, PCD is a normal component of development. We find that
      Salmonella typhimurium colonization of the C. elegans intestine leads to an
      increased level of cell death in the worm gonad. S. typhimurium-mediated germ
      line cell death is not observed in C. elegans ced-3 and ced-4 mutants in which
      developmentally regulated cell death is blocked, and ced-3 and ced-4 mutants are
      hypersensitive to S. typhimurium-mediated killing. These results suggest that PCD
      may be involved in the C. elegans defense response to pathogen attack.

PMID- 11226310
TI  - Comparative genomics of the restriction-modification systems in Helicobacter
      pylori.
AB  - Helicobacter pylori is a Gram-negative bacterial pathogen with a small genome of
      1.64-1.67 Mb. More than 20 putative DNA restriction-modification (R-M) systems,
      comprising more than 4% of the total genome, have been identified in the two
      completely sequenced H. pylori strains, 26695 and J99, based on sequence
      similarities. In this study, we have investigated the biochemical activities of
      14 Type II R-M systems in H. pylori 26695. Less than 30% of the Type II R-M
      systems in 26695 are fully functional, similar to the results obtained from
      strain J99. Although nearly 90% of the R-M genes are shared by the two H. pylori
      strains, different sets of these R-M genes are functionally active in each
      strain. Interestingly, all strain-specific R-M genes are active, whereas most
      shared genes are inactive. This agrees with the notion that strain-specific genes
      have been acquired more recently through horizontal transfer from other bacteria
      and selected for function. Thus, they are less likely to be impaired by random
      mutations. Our results also show that H. pylori has extremely diversified R-M
      systems in different strains, and that the diversity may be maintained by
      constantly acquiring new R-M systems and by inactivating and deleting the old
      ones.

PMID- 11226311
TI  - Sequence of the 1918 pandemic influenza virus nonstructural gene (NS) segment and
      characterization of recombinant viruses bearing the 1918 NS genes.
AB  - The influenza A virus pandemic of 1918-1919 resulted in an estimated 20-40
      million deaths worldwide. The hemagglutinin and neuraminidase sequences of the
      1918 virus were previously determined. We here report the sequence of the
      A/Brevig Mission/1/18 (H1N1) virus nonstructural (NS) segment encoding two
      proteins, NS1 and nuclear export protein. Phylogenetically, these genes appear to
      be close to the common ancestor of subsequent human and classical swine strain NS
      genes. Recently, the influenza A virus NS1 protein was shown to be a type I IFN
      antagonist that plays an important role in viral pathogenesis. By using the
      recently developed technique of generating influenza A viruses entirely from
      cloned cDNAs, the hypothesis that the 1918 virus NS1 gene played a role in
      virulence was tested in a mouse model. In a BSL3+ laboratory, viruses were
      generated that possessed either the 1918 NS1 gene alone or the entire 1918 NS
      segment in a background of influenza A/WSN/33 (H1N1), a mouse-adapted virus
      derived from a human influenza strain first isolated in 1933. These 1918 NS
      viruses replicated well in tissue culture but were attenuated in mice as compared
      with the isogenic control viruses. This attenuation in mice may be related to the
      human origin of the 1918 NS1 gene. These results suggest that interaction of the
      NS1 protein with host-cell factors plays a significant role in viral
      pathogenesis.

PMID- 11226312
TI  - QscR, a modulator of quorum-sensing signal synthesis and virulence in Pseudomonas
      aeruginosa.
AB  - The opportunistic pathogenic bacterium Pseudomonas aeruginosa uses quorum-sensing
      signaling systems as global regulators of virulence genes. There are two quorum
      sensing signal receptor and signal generator pairs, LasR-LasI and RhlR-RhlI. The
      recently completed P. aeruginosa genome-sequencing project revealed a gene coding
      for a homolog of the signal receptors, LasR and RhlR. Here we describe a role for
      this gene, which we call qscR. The qscR gene product governs the timing of quorum
      sensing-controlled gene expression and it dampens virulence in an insect model.
      We present evidence that suggests the primary role of QscR is repression of lasI.
      A qscR mutant produces the LasI-generated signal prematurely, and this results in
      premature transcription of a number of quorum-sensing-regulated genes. When fed
      to Drosophila melanogaster, the qscR mutant kills the animals more rapidly than
      the parental P. aeruginosa. The repression of lasI by QscR could serve to ensure
      that quorum-sensing-controlled genes are not activated in environments where they
      are not useful.

PMID- 11226313
TI  - Effect of rabies virus infection on gene expression in mouse brain.
AB  - A variety of molecular genetic approaches were used to study the effect of rabies
      virus (RV) infection on host gene expression in mouse brain. The down-regulation
      of gene expression was found to be a major effect of RV infection by using
      subtraction hybridization. However, a combination of techniques identified
      approximately 39 genes activated by infection. These included genes involved in
      regulation of cell metabolism, protein synthesis, synaptic activity, and cell
      growth and differentiation. Northern blot analysis to monitor temporal activation
      of several of these genes following infection revealed essentially two patterns
      of activation: (i) an early response with up-regulation beginning within 3 days
      after infection and correlating with transcription of RV nuclear protein; and
      (ii) a late response with enhanced expression occurring at days 6-7 after
      infection and associated with peak RV replication. The gene activation patterns
      and the known functions of their products suggest that a number of host genes may
      be involved in the replication and spread of RV in the brain.

PMID- 11226314
TI  - Synergistic contributions of cyclin-dependant kinase 5/p35 and Reelin/Dab1 to the
      positioning of cortical neurons in the developing mouse brain.
AB  - Cyclin-dependent kinase (Cdk) 5 is a unique member of the Cdk family, because
      Cdk5 kinase activity is detected only in the nervous tissue. Two neuron-specific
      activating subunits of Cdk5, p35 and p39, have been identified. Overlapping
      expression pattern of these isoforms in the embryonic mouse brain and the
      significant residual Cdk5 kinase activity in brain homogenate of the p35-/- mice
      indicate the redundant functions of the Cdk5 activators in vivo. Severe neuronal
      migration defects in p35-/-Cdk5 +/- mice further support the idea that the
      redundant expression of the Cdk5 activators may cause a milder phenotype in p35-/
      mice compared with Cdk5-/- mice. Mutant mice lacking either Cdk5 or p35 exhibit
      certain similarities with Reelin/Dab1-mutant mice in the disorganization of
      cortical laminar structure in the brain. To elucidate the relationship between
      Cdk5/p35 and Reelin/Dab1 signaling, we generated mouse lines that have combined
      defects of these genes. The addition of heterozygosity of either Dab1 or Reelin
      mutation to p35-/- causes the extensive migration defects of cortical neurons in
      the cerebellum. In the double-null mice of p35 and either Dab1 or Reelin,
      additional migration defects occur in the Purkinje cells in the cerebellum and in
      the pyramidal neurons in the hippocampus. These additional defects in neuronal
      migration in mice lacking both Cdk5/p35 and Reelin/Dab1 indicate that Cdk5/p35
      may contribute synergistically to the positioning of the cortical neurons in the
      developing mouse brain.

PMID- 11226315
TI  - Internal initiation of translation of five dendritically localized neuronal
      mRNAs.
AB  - In neurons, translation of dendritically localized mRNAs is thought to play a
      role in affecting synaptic efficacy. Inasmuch as components of the translation
      machinery may be limiting in dendrites, we investigated the mechanisms by which
      translation of five dendritically localized mRNAs is initiated. The 5' leader
      sequences of mRNAs encoding the activity-regulated cytoskeletal protein, the
      alpha subunit of calcium-calmodulin-dependent kinase II, dendrin, the microtubule
      associated protein 2, and neurogranin (RC3) were evaluated for their ability to
      affect translation in the 5' untranslated region of a monocistronic reporter
      mRNA. In both neural and nonneural cell lines, the activity-regulated
      cytoskeletal protein, microtubule-associated protein 2, and alpha-CaM Kinase II
      leader sequences enhanced translation, whereas the dendrin and RC3 5'
      untranslated regions slightly inhibited translation as compared with controls.
      When cap-dependent translation of these constructs was suppressed by
      overexpression of a protein that binds the cap-binding protein eIF4E, it was
      revealed that translation of these mRNAs had both cap-dependent and cap
      independent components. The cap-independent component was further analyzed by
      inserting the 5' leader sequences into the intercistronic region of dicistronic
      mRNAs. All five leader sequences mediated internal initiation via internal
      ribosome entry sites (IRESes). The RC3 IRES was most active and was further
      characterized after transfection in primary neurons. Although translation
      mediated by this IRES occurred throughout the cell, it was relatively more
      efficient in dendrites. These data suggest that IRESes may increase translation
      efficiency at postsynaptic sites after synaptic activation.

PMID- 11226316
TI  - Coinciding early activation of the human primary visual cortex and anteromedial
      cuneus.
AB  - Proper understanding of processes underlying visual perception requires
      information on the activation order of distinct brain areas. We measured dynamics
      of cortical signals with magnetoencephalography while human subjects viewed
      stimuli at four visual quadrants. The signals were analyzed with minimum current
      estimates at the individual and group level. Activation emerged 55-70 ms after
      stimulus onset both in the primary posterior visual areas and in the anteromedial
      part of the cuneus. Other cortical areas were active after this initial dual
      activation. Comparison of data between species suggests that the anteromedial
      cuneus either comprises a homologue of the monkey area V6 or is an area unique to
      humans. Our results show that visual stimuli activate two cortical areas right
      from the beginning of the cortical response. The anteromedial cuneus has the
      temporal position needed to interact with the primary visual cortex V1 and
      thereby to modify information transferred via V1 to extrastriate cortices.

PMID- 11226317
TI  - Characteristics of glycine receptors expressed by embryonic rat brain mRNAs.
AB  - A study was made of glycine (Gly) and gamma-aminobutyric acid (GABA) receptors
      expressed in Xenopus oocytes injected with rat mRNAs isolated from the
      encephalon, midbrain, and brainstem of 18-day-old rat embryos. In oocytes
      injected with encephalon, midbrain, or brainstem mRNAs, the Gly-current
      amplitudes (membrane current elicited by Gly; 1 mM Gly) were respectively 115 +/-
      35, 346 +/- 28, and 389 +/- 22 nA, whereas the GABA-currents (1 mM GABA) were all
      < or =40 nA. Moreover, the Gly-currents desensitized faster in oocytes injected
      with encephalon or brainstem mRNAs. The EC(50) for Gly was 611 +/- 77 microM for
      encephalon, 661 +/- 28 microM for midbrain, and 506 +/- 18 microM for brainstem
      mRNA-injected oocytes, and the corresponding Hill coefficients were all
      approximately 2. Strychnine inhibited all of the Gly-currents, with an IC(50) of
      56 +/- 3 nM for encephalon, 97 +/- 4 nM for midbrain, and 72 +/- 4 nM for
      brainstem mRNAs. During repetitive Gly applications, the Gly-currents were
      potentiated by 1.6-fold for encephalon, 2.1-fold for midbrain, and 1.3-fold for
      brainstem RNA-injected oocytes. Raising the extracellular Ca(2+) concentration
      significantly increased the Gly-currents in oocytes injected with midbrain and
      brainstem mRNAs. Reverse transcription-PCR studies showed differences in the Gly
      receptor (GlyR) alpha-subunits expressed, whereas the beta-subunit was present in
      all three types of mRNA. These results indicate differential expression of GlyR
      mRNAs in the brain areas examined, and these mRNAs lead to the expression of
      GlyRs that have different properties. The modulation of GlyRs by Ca(2+) could
      play important functions during brain development.

PMID- 11226318
TI  - Point mutant mice with hypersensitive alpha 4 nicotinic receptors show
      dopaminergic deficits and increased anxiety.
AB  - Knock-in mice were generated that harbored a leucine-to-serine mutation in the
      alpha4 nicotinic receptor near the gate in the channel pore. Mice with intact
      expression of this hypersensitive receptor display dominant neonatal lethality.
      These mice have a severe deficit of dopaminergic neurons in the substantia nigra,
      possibly because the hypersensitive receptors are continuously activated by
      normal extracellular choline concentrations. A strain that retains the neo
      selection cassette in an intron has reduced expression of the hypersensitive
      receptor and is viable and fertile. The viable mice display increased anxiety,
      poor motor learning, excessive ambulation that is eliminated by very low levels
      of nicotine, and a reduction of nigrostriatal dopaminergic function upon aging.
      These knock-in mice provide useful insights into the pathophysiology of sustained
      nicotinic receptor activation and may provide a model for Parkinson's disease.

PMID- 11226319
TI  - Morphological abnormalities in the brains of estrogen receptor beta knockout
      mice.
AB  - Estrogen receptor beta (ERbeta) is expressed at high levels in both neurons and
      glial cells of the central nervous system. The development of ERbeta knockout
      (BERKO) mice has provided a model to study the function of this nuclear receptor
      in the brain. We have found that the brains of BERKO mice show several
      morphological abnormalities. There is a regional neuronal hypocellularity in the
      brain, with a severe neuronal deficit in the somatosensory cortex, especially
      layers II, III, IV, and V, and a remarkable proliferation of astroglial cells in
      the limbic system but not in the cortex. These abnormalities are evident as early
      as 2 mo of age in BERKO mice. As BERKO mice age, the neuronal deficit becomes
      more pronounced, and, by 2 yr of age, there is degeneration of neuronal cell
      bodies throughout the brain. This is particularly evident in the substantia
      nigra. We conclude that ERbeta is necessary for neuronal survival and speculate
      that this gene could have an important influence on the development of
      degenerative diseases of the central nervous system, such as Alzheimer's disease
      and Parkinson's disease, as well as those resulting from trauma and stroke in the
      brain.

PMID- 11226320
TI  - Theory for normal and impaired experience-dependent plasticity in neocortex of
      adult rats.
AB  - We model experience-dependent plasticity in the cortical representation of
      whiskers (the barrel cortex) in normal adult rats, and in adult rats that were
      prenatally exposed to alcohol. Prenatal exposure to alcohol (PAE) caused marked
      deficits in experience-dependent plasticity in a cortical barrel-column. Cortical
      plasticity was induced by trimming all whiskers on one side of the face except
      two. This manipulation produces high activity from the intact whiskers that
      contrasts with low activity from the cut whiskers while avoiding any nerve
      damage. By a computational model, we show that the evolution of neuronal
      responses in a single barrel-column after this sensory bias is consistent with
      the synaptic modifications that follow the rules of the Bienenstock, Cooper, and
      Munro (BCM) theory. The BCM theory postulates that a neuron possesses a moving
      synaptic modification threshold, theta(M), that dictates whether the neuron's
      activity at any given instant will lead to strengthening or weakening of its
      input synapses. The current value of theta(M) changes proportionally to the
      square of the neuron's activity averaged over some recent past. In the model of
      alcohol impaired cortex, the effective theta(M) has been set to a level
      unattainable by the depressed levels of cortical activity leading to "impaired"
      synaptic plasticity that is consistent with experimental findings. Based on
      experimental and computational results, we discuss how elevated theta(M) may be
      related to (i) reduced levels of neurotransmitters modulating plasticity, (ii)
      abnormally low expression of N-methyl-d-aspartate receptors (NMDARs), and (iii)
      the membrane translocation of Ca(2+)/calmodulin-dependent protein kinase II
      (CaMKII) in adult rat cortex subjected to prenatal alcohol exposure.

PMID- 11226321
TI  - Tonic nicotinic modulation of serotoninergic transmission in the spinal cord.
AB  - The spinal serotoninergic projection from the raphe magnus has been shown to
      modulate nociceptive inputs, and activation of this projection mediates nicotine
      elicited analgesia. Here, we investigate the interactions between cholinergic and
      serotoninergic systems in the spinal cord, by conducting serotonin [5
      hydroxytryptamine (5-HT)] efflux experiments on mouse spinal slices. At least
      three spinal populations of nicotinic receptors are distinguished that affect 5
      HT release. The first could be directly located on serotoninergic terminals, is
      insensitive to nanomolar concentrations of methyllicaconitine (MLA), and may be
      subjected to a basal (not maximal) cholinergic tone. The second is tonically and
      maximally activated by endogenous acetylcholine, insensitive to nanomolar
      concentrations of MLA, and present on inhibitory neurons. The last is also
      present on inhibitory neurons but is sensitive to nanomolar concentrations of MLA
      and not tonically activated by acetylcholine. Multiple nicotinic acetylcholine
      receptor populations thus differentially exert tonic or not tonic control on 5-HT
      transmission in the spinal cord. These receptors may be major targets for
      nicotine effects on antinociception. In addition, the presence of a tonic
      nicotinic modulation of 5-HT release indicates that endogenous acetylcholine
      plays a role in the physiological regulation of descending 5-HT pathways to the
      spinal cord.

PMID- 11226322
TI  - Activity-dependent CREB phosphorylation: convergence of a fast, sensitive
      calmodulin kinase pathway and a slow, less sensitive mitogen-activated protein
      kinase pathway.
AB  - The cAMP-responsive element binding protein (CREB), a key regulator of gene
      expression, is activated by phosphorylation on Ser-133. Several different protein
      kinases possess the capability of driving this phosphorylation, making it a point
      of potential convergence for multiple intracellular signaling cascades. Previous
      work in neurons has indicated that physiologic synaptic stimulation recruits a
      fast calmodulin kinase IV (CaMKIV)-dependent pathway that dominates early
      signaling to CREB. Here we show in hippocampal neurons that the fast, CaMK
      dependent pathway can be followed by a slower pathway that depends on Ras/mitogen
      activated protein kinase (MAPK), along with CaMK. This pathway was blocked by
      dominant-negative Ras and was specifically recruited by depolarizations that
      produced strong intracellular Ca(2+) transients. When both pathways were
      recruited, phosphorylated CREB (pCREB) formation was overwhelmingly dominated by
      the CaMK pathway between 0 and 10 min, and by the MAPK pathway at 60 min, whereas
      the two pathways acted in concert at 30 min. The Ca(2+) signals that produced
      only rapid CaMK signaling to pCREB or both rapid CaMK and slow MAPK signaling
      deviated significantly for only approximately 1 min, yet their differential
      impact on pCREB extended over a much longer period, between 20 and 60 min and
      beyond, which is of likely significance for gene expression. The CaMK-dependent
      MAPK pathway may inform the nucleus about stimulus amplitude. In contrast, the
      CaMKIV pathway may be well suited to conveying information on the precise timing
      of localized synaptic stimuli, befitting its greater speed and sensitivity,
      whereas the previously described calcineurin pathway may carry information about
      stimulus duration.

PMID- 11226323
TI  - An orchestrated gene expression component of neuronal programmed cell death
      revealed by cDNA array analysis.
AB  - Programmed cell death (PCD) during neuronal development and disease has been
      shown to require de novo RNA synthesis. However, the time course and regulation
      of target genes is poorly understood. By using a brain-biased array of over 7,500
      cDNAs, we profiled this gene expression component of PCD in cerebellar granule
      neurons challenged separately by potassium withdrawal, combined potassium and
      serum withdrawal, and kainic acid administration. We found that hundreds of genes
      were significantly regulated in discreet waves including known genes whose
      protein products are involved in PCD. A restricted set of genes was regulated by
      all models, providing evidence that signals inducing PCD can regulate large
      assemblages of genes (of which a restricted subset may be shared in multiple
      pathways).

PMID- 11226324
TI  - Localization and regulation of GLUTx1 glucose transporter in the hippocampus of
      streptozotocin diabetic rats.
AB  - We describe the localization of the recently identified glucose transporter
      GLUTx1 and the regulation of GLUTx1 in the hippocampus of diabetic and control
      rats. GLUTx1 mRNA and protein exhibit a unique distribution when compared with
      other glucose transporter isoforms expressed in the rat hippocampus. In
      particular, GLUTx1 mRNA was detected in hippocampal pyramidal neurons and granule
      neurons of the dentate gyrus as well as in nonprincipal neurons. With
      immunohistochemistry, GLUTx1 protein expression is limited to neuronal cell
      bodies and the most proximal dendrites, unlike GLUT3 expression that is observed
      throughout the neuropil. Immunoblot analysis of hippocampal membrane fractions
      revealed that GLUTx1 protein expression is primarily localized to the
      intracellular compartment and exhibits limited association with the plasma
      membrane. In streptozotocin diabetic rats compared with vehicle-treated controls,
      quantitative autoradiography showed increased GLUTx1 mRNA levels in pyramidal
      neurons and granule neurons; up-regulation of GLUTx1 mRNA also was found in
      nonprincipal cells, as shown by single-cell emulsion autoradiography. In
      contrast, diabetic and control rats expressed similar levels of hippocampal
      GLUTx1 protein. These results indicate that GLUTx1 mRNA and protein have a unique
      expression pattern in rat hippocampus and suggest that streptozotocin diabetes
      increases steady-state mRNA levels in the absence of concomitant increases in
      GLUTx1 protein expression.

PMID- 11226325
TI  - In vivo evidence for a cochlear amplifier in the hair-cell bundle of lizards.
AB  - Vertebrate sensory hair cells achieve high sensitivity and frequency selectivity
      by adding self-generated mechanical energy to low-level signals. This allows them
      to detect signals that are smaller than thermal molecular motion and to achieve
      significant resonance amplitudes and frequency selectivity despite the viscosity
      of the surrounding fluid. In nonmammals, a great deal of in vitro evidence
      indicates that the active process responsible for this amplification is
      intimately associated with the hair cells' transduction channels in the
      stereovillar bundle. Here, we provide in vivo evidence of hair-cell bundle
      involvement in active processes. Electrical stimulation of the inner ear of a
      lizard at frequencies typical for this hearing organ induced low-level
      otoacoustic emissions that could be modulated by low-frequency sound. The unique
      modulation pattern permitted the tracing of the active process involved to the
      stereovillar bundles of the sensory hair cells. This supports the notion that, in
      nonmammals, the cochlear amplifier in the hair cells is driven by a bundle motor
      system.

PMID- 11226326
TI  - beta -Neuregulin-1 is required for the in vivo development of functional Ca2+
      activated K+ channels in parasympathetic neurons.
AB  - The development of functional Ca(2+)-activated K(+) channels (K(Ca)) in chick
      ciliary ganglion (CG) neurons requires interactions with afferent preganglionic
      nerve terminals. Here we show that the essential preganglionic differentiation
      factor is an isoform of beta-neuregulin-1. beta-Neuregulin-1 transcripts are
      expressed in the midbrain preganglionic Edinger-Westphal nucleus at developmental
      stages that coincide with or precede the normal onset of macroscopic K(Ca) in CG
      neurons. Injection of beta-neuregulin-1 peptide into the brains of developing
      embryos evoked a robust stimulation of functional K(Ca) channels at stages before
      the normal appearance of these channels in CG neurons developing in vivo.
      Conversely, injection of a neutralizing antiserum specific for beta-neuregulin-1
      inhibited the development of K(Ca) channels in CG neurons. Low concentrations of
      beta-neuregulin-1 evoked a robust increase in whole-cell K(Ca) in CG neurons
      cocultured with iris target tissues. By contrast, culturing CG neurons with iris
      cells or low concentrations of beta-neuregulin-1 by themselves was insufficient
      to stimulate K(Ca). These data suggest that the preganglionic factor required for
      the development of K(Ca) in ciliary ganglion neurons is an isoform of beta
      neuregulin-1, and that this factor acts in concert with target-derived trophic
      molecules to regulate the differentiation of excitability.

PMID- 11226327
TI  - Bax ablation prevents dopaminergic neurodegeneration in the 1-methyl- 4-phenyl
      1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease.
AB  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) damages dopaminergic neurons
      in the substantia nigra pars compacta (SNpc) as seen in Parkinson's disease.
      Here, we show that the pro-apoptotic protein Bax is highly expressed in the SNpc
      and that its ablation attenuates SNpc developmental neuronal apoptosis. In adult
      mice, there is an up-regulation of Bax in the SNpc after MPTP administration and
      a decrease in Bcl-2. These changes parallel MPTP-induced dopaminergic
      neurodegeneration. We also show that mutant mice lacking Bax are significantly
      more resistant to MPTP than their wild-type littermates. This study demonstrates
      that Bax plays a critical role in the MPTP neurotoxic process and suggests that
      targeting Bax may provide protective benefit in the treatment of Parkinson's
      disease.

PMID- 11226329
TI  - Brain 5alpha-dihydroprogesterone and allopregnanolone synthesis in a mouse model
      of protracted social isolation.
AB  - Allopregnanolone (ALLO), is a brain endogenous neurosteroid that binds with high
      affinity to gamma-aminobutyric acid type A (GABA(A)) receptors and positively
      modulates the action of GABA at these receptors. Unlike ALLO, 5alpha
      dihydroprogesterone (5alpha-DHP) binds with high affinity to intracellular
      progesterone receptors that regulate DNA transcription. To investigate the
      physiological roles of ALLO and 5alpha-DHP synthesized in brain, we have adopted
      a mouse model involving protracted social isolation. In the frontal cortex of
      mice, socially isolated for 6 weeks, both neurosteroids were decreased by
      approximately 50%. After administration of (17beta)-17-(bis-1-methyl amino
      carbonyl) androstane-3,5-diene-3-carboxylic acid (SKF105,111), an inhibitor of
      the enzyme (5alpha-reductase Type I and II) that converts progesterone into
      5alpha-DHP, the ALLO and 5alpha-DHP content of frontal cortex of both group
      housed and socially isolated mice decreased exponentially to 10%-20% of control
      values in about 30 min. The fractional rate constants (k h(-1)) of ALLO and
      5alpha-DHP decline multiplied by the ALLO and 5alpha-DHP concentrations at any
      given steady-state estimate the rate of synthesis required to maintain that
      steady state. After 6 weeks of social isolation, ALLO and 5alpha-DHP biosynthesis
      rates were decreased to 30% of the values calculated in group-housed mice.
      Moreover, in socially isolated mice, the expression of 5alpha-reductase Type I
      mRNA and protein was approximately 50% lower than in group-housed mice whereas
      3alpha-hydroxysteroid oxidoreductase mRNA expression was equal in the two groups.
      Protracted social isolation in mice may provide a model to investigate whether
      5alpha-DHP by a genomic action, and ALLO by a nongenomic mechanism down-regulate
      the action of drugs acting as agonists, partial agonists, or positive allosteric
      modulators of the benzodiazepine recognition sites expressed by GABA(A)
      receptors.

PMID- 11226328
TI  - Urocortin II: a member of the corticotropin-releasing factor (CRF) neuropeptide
      family that is selectively bound by type 2 CRF receptors.
AB  - Here we describe the cloning and initial characterization of a previously
      unidentified CRF-related neuropeptide, urocortin II (Ucn II). Searches of the
      public human genome database identified a region with significant sequence
      homology to the CRF neuropeptide family. By using homologous primers deduced from
      the human sequence, a mouse cDNA was isolated from whole brain poly(A)(+) RNA
      that encodes a predicted 38-aa peptide, structurally related to the other known
      mammalian family members, CRF and Ucn. Ucn II binds selectively to the type 2 CRF
      receptor (CRF-R2), with no appreciable activity on CRF-R1. Transcripts encoding
      Ucn II are expressed in discrete regions of the rodent central nervous system,
      including stress-related cell groups in the hypothalamus (paraventricular and
      arcuate nuclei) and brainstem (locus coeruleus). Central administration of 1-10
      microg of peptide elicits activational responses (Fos induction) preferentially
      within a core circuitry subserving autonomic and neuroendocrine regulation, but
      whose overall pattern does not broadly mimic the CRF-R2 distribution.
      Behaviorally, central Ucn II attenuates nighttime feeding, with a time course
      distinct from that seen in response to CRF. In contrast to CRF, however, central
      Ucn II failed to increase gross motor activity. These findings identify Ucn II as
      a new member of the CRF family of neuropeptides, which is expressed centrally and
      binds selectively to CRF-R2. Initial functional studies are consistent with Ucn
      II involvement in central autonomic and appetitive control, but not in
      generalized behavioral activation.

PMID- 11226330
TI  - Coupling of histamine H3 receptors to neuronal Na+/H+ exchange: a novel
      protective mechanism in myocardial ischemia.
AB  - In myocardial ischemia, adrenergic nerves release excessive amounts of
      norepinephrine (NE), causing dysfunction and arrhythmias. With anoxia and the
      concomitant ATP depletion, vesicular storage of NE is impaired, resulting in
      accumulation of free NE in the axoplasm of sympathetic nerves. Intraneuronal
      acidosis activates the Na(+)/H(+) exchanger (NHE), leading to increased Na(+)
      entry in the nerve terminals. These conditions favor availability of the NE
      transporter to the axoplasmic side of the membrane, causing massive carrier
      mediated efflux of free NE. Neuronal NHE activation is pivotal in this process;
      NHE inhibitors attenuate carrier-mediated NE release. We previously reported that
      activation of histamine H(3) receptors (H(3)R) on cardiac sympathetic nerves also
      reduces carrier-mediated NE release and alleviates arrhythmias. Thus, H(3)R
      activation may be negatively coupled to NHE. We tested this hypothesis in
      individual human SKNMC neuroblastoma cells stably transfected with H(3)R cDNA,
      loaded with the intracellular pH (pH(i)) indicator BCECF. These cells possess
      amiloride-sensitive NHE. NHE activity was measured as the rate of Na(+)-dependent
      pH(i) recovery in response to an acute acid pulse (NH(4)Cl). We found that the
      selective H(3)R-agonist imetit markedly diminished NHE activity, and so did the
      amiloride derivative EIPA. The selective H(3)R antagonist thioperamide abolished
      the imetit-induced NHE attenuation. Thus, our results provide a link between
      H(3)R and NHE, which may limit the excessive release of NE during protracted
      myocardial ischemia. Our previous and present findings uncover a novel mechanism
      of cardioprotection: NHE inhibition in cardiac adrenergic neurons as a means to
      prevent ischemic arrhythmias associated with carrier-mediated NE release.

PMID- 11226331
TI  - Effects of nitric oxide-releasing aspirin versus aspirin on restenosis in
      hypercholesterolemic mice.
AB  - Restenosis is due to neointimal hyperplasia, which occurs in the coronary artery
      after percutaneous transluminal coronary angioplasty (PTCA). During restenosis,
      an impairment of nitric oxide (NO)-dependent pathways may occur. Concomitant
      hypercholesterolemia may exacerbate restenosis in patients undergoing PTCA. Here,
      we show that a NO-releasing aspirin derivative (NCX-4016) reduces the degree of
      restenosis after balloon angioplasty in low-density lipoprotein receptor
      deficient mice and this effect is associated with reduced vascular smooth muscle
      cell (VSMC) proliferation and macrophage deposition at the site of injury. Drugs
      were administered following both therapeutic or preventive protocols. We
      demonstrate that NCX-4016 is effective both in prevention and treatment of
      restenosis in the presence of hypercholesterolemia. These data indicate that
      impairment of NO-dependent mechanisms may be involved in the development of
      restenosis in hypercholesterolemic mice. Although experimental models of
      restenosis may not reflect restenosis in humans in all details, we suggest that a
      NO-releasing aspirin derivative could be an effective drug in reducing restenosis
      following PTCA, especially in the presence of hypercholesterolemia and/or
      gastrointestinal damage.

PMID- 11226332
TI  - Ryanodine receptor point mutant E4032A reveals an allosteric interaction with
      ryanodine.
AB  - The ryanodine receptor (RyR) family of proteins constitutes a unique type of
      calcium channel that mediates Ca(2+) release from endoplasmic
      reticulum/sarcoplasmic reticulum stores. Ryanodine has been widely used to
      identify contributions made by the RyR to signaling in both muscle and nonmuscle
      cells. Ryanodine, through binding to high- and low-affinity sites, has been
      suggested to block the channel pore based on its ability to induce partial
      conductance states and irreversible inhibition. We examined the effect of
      ryanodine on an RyR type 1 (RyR1) point mutant (E4032A) that exhibits a severely
      compromised phenotype. When expressed in 1B5 (RyR null/dyspedic) myotubes, E4032A
      is relatively unresponsive to stimulation by cell membrane depolarization or RyR
      agonists, although the full-length protein is correctly targeted to junctions and
      interacts with dihydropyridine receptors (DHPRs) inducing their arrangement into
      tetrads. However, treatment of E4032A-expressing cells with 200-500 microM
      ryanodine, concentrations that rapidly activate and then inhibit wild-type (wt)
      RyR1, restores the responsiveness of E4032A-expressing myotubes to depolarization
      and RyR agonists. Moreover, the restored E4032A channels remain resistant to
      subsequent exposure to ryanodine. In single-channel studies, E4032A exhibits
      infrequent (channel-open probability, P(o) < 0.005) and brief (<250 micros)
      gating events and insensitivity to Ca(2+). Addition of ryanodine restores Ca(2+)
      dependent channel activity exhibiting full, 3/4, 1/2, and 1/4 substates. This
      evidence suggests that, whereas ryanodine does not occlude the RyR pore, it does
      bind to sites that allosterically induce substantial conformational changes in
      the RyR. In the case of E4032A, these changes overcome unfavorable energy
      barriers introduced by the E4032A mutation to restore channel function.

PMID- 11226333
TI  - Inhibition of caspase 1 reduces human myocardial ischemic dysfunction via
      inhibition of IL-18 and IL-1beta.
AB  - The proinflammatory cytokine IL-18 was investigated for its role in human
      myocardial function. An ischemia/reperfusion (I/R) model of suprafused human
      atrial myocardium was used to assess myocardial contractile force. Addition of IL
      18 binding protein (IL-18BP), the constitutive inhibitor of IL-18 activity, to
      the perifusate during and after I/R resulted in improved contractile function
      after I/R from 35% of control to 76% with IL-18BP. IL-18BP treatment also
      preserved intracellular tissue creatine kinase levels (by 420%). Steady-state
      mRNA levels for IL-18 were elevated after I/R, and the concentration of IL-18 in
      myocardial homogenates was increased (control, 5.8 pg/mg vs. I/R, 26 pg/mg; P <
      0.01). Active IL-18 requires cleavage of its precursor form by the IL-1beta
      converting enzyme (caspase 1); inhibition of caspase 1 also attenuated the
      depression in contractile force after I/R (from 35% of control to 75.8% in
      treated atrial muscle; P < 0.01). Because caspase 1 also cleaves the precursor IL
      1beta, IL-1 receptor blockade was accomplished by using the IL-1 receptor
      antagonist. IL-1 receptor antagonist added to the perifusate also resulted in a
      reduction of ischemia-induced contractile dysfunction. These studies demonstrate
      that endogenous IL-18 and IL-1beta play a significant role in I/R-induced human
      myocardial injury and that inhibition of caspase 1 reduces the processing of
      endogenous precursors of IL-18 and IL-1beta and thereby prevents ischemia-induced
      myocardial dysfunction.

PMID- 11226334
TI  - Calmodulin kinase is a molecular switch for cardiac excitation-contraction
      coupling.
AB  - Signaling between cell membrane-bound L-type Ca(2+) channels (LTCC) and ryanodine
      receptor Ca(2+) release channels (RyR) on sarcoplasmic reticulum (SR) stores
      grades excitation-contraction coupling (ECC) in striated muscle. A physical
      connection regulates LTCC and RyR in skeletal muscle, but the molecular mechanism
      for coordinating LTCC and RyR in cardiomyocytes, where this physical link is
      absent, is unknown. Calmodulin kinase (CaMK) has characteristics suitable for an
      ECC coordinating molecule: it is activated by Ca(2+)/calmodulin, it regulates
      LTCC and RyR, and it is enriched in the vicinity of LTCC and RyR. Intact
      cardiomyocytes were studied under conditions where CaMK activity could be
      controlled independently of intracellular Ca(2+) by using an engineered Ca(2+)
      independent form of CaMK and a highly specific CaMK inhibitory peptide. CaMK
      reciprocally enhanced L-type Ca(2+) current and reduced release of Ca(2+) from
      the SR while increasing SR Ca(2+) content. These findings support the hypothesis
      that CaMK is required to functionally couple LTCC and RyR during cardiac ECC.

PMID- 11226335
TI  - Defective trafficking and function of KATP channels caused by a sulfonylurea
      receptor 1 mutation associated with persistent hyperinsulinemic hypoglycemia of
      infancy.
AB  - The ATP-sensitive potassium channel (K(ATP)) regulates insulin secretion in
      pancreatic beta cells. Loss of functional K(ATP) channels because of mutations in
      either the SUR1 or Kir6.2 channel subunit causes persistent hyperinsulinemic
      hypoglycemia of infancy (PHHI). We investigated the molecular mechanism by which
      a single phenylalanine deletion in SUR1 (DeltaF1388) causes PHHI. Previous
      studies have shown that coexpression of DeltaF1388 SUR1 with Kir6.2 results in no
      channel activity. We demonstrate here that the lack of functional expression is
      due to failure of the mutant channel to traffic to the cell surface. Trafficking
      of K(ATP) channels requires that the endoplasmic reticulum-retention signal, RKR,
      present in both SUR1 and Kir6.2, be shielded during channel assembly. To ask
      whether DeltaF1388 SUR1 forms functional channels with Kir6.2, we inactivated the
      RKR signal in DeltaF1388 SUR1 by mutation to AAA (DeltaF1388 SUR1(AAA)).
      Inactivation of similar endoplasmic reticulum-retention signals in the cystic
      fibrosis transmembrane conductance regulator has been shown to partially overcome
      the trafficking defect of a cystic fibrosis transmembrane conductance regulator
      mutation, DeltaF508. We found that coexpression of DeltaF1388 SUR1(AAA) with
      Kir6.2 led to partial surface expression of the mutant channel. Moreover, mutant
      channels were active. Compared with wild-type channels, the mutant channels have
      reduced ATP sensitivity and do not respond to stimulation by MgADP or diazoxide.
      The RKR --> AAA mutation alone has no effect on channel properties. Our results
      establish defective trafficking of K(ATP) channels as a molecular basis of PHHI
      and show that F1388 in SUR1 is critical for normal trafficking and function of
      K(ATP) channels.

PMID- 11226336
TI  - Reconstitution and functional comparison of purified GlpF and AqpZ, the glycerol
      and water channels from Escherichia coli.
AB  - A large family of membrane channel proteins selective for transport of water
      (aquaporins) or water plus glycerol (aquaglyceroporins) has been found in diverse
      life forms. Escherichia coli has two members of this family-a water channel,
      AqpZ, and a glycerol facilitator, GlpF. Despite having similar primary amino acid
      sequences and predicted structures, the oligomeric state and solute selectivity
      of AqpZ and GlpF are disputed. Here we report biochemical and functional
      characterizations of affinity-purified GlpF and compare it to AqpZ. Histidine
      tagged (His-GlpF) and hemagglutinin-tagged (HA-GlpF) polypeptides encoded by a
      bicistronic construct were expressed in bacteria. HA-GlpF and His-GlpF appear to
      form oligomers during Ni-nitrilotriacetate affinity purification. Sucrose
      gradient sedimentation analyses showed that the oligomeric state of octyl
      glucoside-solubilized GlpF varies: low ionic strength favors subunit
      dissociation, whereas Mg(2+) stabilizes tetrameric assembly. Reconstitution of
      affinity-purified GlpF into proteoliposomes increases glycerol permeability more
      than 100-fold and water permeability up to 10-fold compared with control
      liposomes. Glycerol and water permeability of GlpF both occur with low Arrhenius
      activation energies and are reversibly inhibited by HgCl(2). Our studies
      demonstrate that, unlike AqpZ, a water-selective stable tetramer, purified GlpF
      exists in multiple oligomeric forms under nondenaturing conditions and is highly
      permeable to glycerol but less well permeated by water.

PMID- 11226337
TI  - Altered ubiquitination and stability of aquaporin-1 in hypertonic stress.
AB  - Aquaporin-1 (AQP1) water channel protein expression is increased by hypertonic
      stress. The contribution of changes in protein stability to hypertonic induction
      of AQP1 have not been described. Incubation of BALB/c fibroblasts spontaneously
      expressing AQP1 with proteasome inhibitors increased AQP1 expression, suggesting
      basal proteasome-dependent degradation of the protein. Degradation by the
      proteasome is thought to be triggered by polyubiquitination of a target protein.
      To determine whether AQP1 is ubiquitinated, immunoprecipitation with anti-AQP1
      antibodies was performed, and the resultant samples were probed by protein
      immunoblot for the presence of ubiquitin. Immunoblots demonstrated ubiquitination
      of AQP1 under control conditions that increased after treatment with proteasome
      inhibitors (MG132, lactacystin). Exposure of cells to hypertonic medium for as
      little as 4 h decreased ubiquitination of AQP1, an effect that persisted through
      24 h in hypertonic medium. Using metabolic labeling with [(35)S]methionine, the
      half-life of AQP1 protein under isotonic conditions was found to be <4 h. AQP1
      protein half-life was markedly increased by exposure of cells to hypertonic
      medium. These observations provide evidence that aquaporins are a target for
      ubiquitination and proteasome-dependent degradation. Additionally, these studies
      demonstrate that reduced protein ubiquitination and increased protein stability
      lead to increased levels of AQP1 expression during hypertonic stress.

PMID- 11226338
TI  - Galactose-extended glycans of antibodies produced by transgenic plants.
AB  - Plant-specific N-glycosylation can represent an important limitation for the use
      of recombinant glycoproteins of mammalian origin produced by transgenic plants.
      Comparison of plant and mammalian N-glycan biosynthesis indicates that beta1,4
      galactosyltransferase is the most important enzyme that is missing for conversion
      of typical plant N-glycans into mammalian-like N-glycans. Here, the stable
      expression of human beta1,4-galactosyltransferase in tobacco plants is described.
      Proteins isolated from transgenic tobacco plants expressing the mammalian enzyme
      bear N-glycans, of which about 15% exhibit terminal beta1,4-galactose residues in
      addition to the specific plant N-glycan epitopes. The results indicate that the
      human enzyme is fully functional and localizes correctly in the Golgi apparatus.
      Despite the fact that through the modified glycosylation machinery numerous
      proteins have acquired unusual N-glycans with terminal beta1,4-galactose
      residues, no obvious changes in the physiology of the transgenic plants are
      observed, and the feature is inheritable. The crossing of a tobacco plant
      expressing human beta1,4-galactosyltransferase with a plant expressing the heavy
      and light chains of a mouse antibody results in the expression of a plantibody
      that exhibits partially galactosylated N-glycans (30%), which is approximately as
      abundant as when the same antibody is produced by hybridoma cells. These results
      are a major step in the in planta engineering of the N-glycosylation of
      recombinant antibodies.

PMID- 11226339
TI  - One ring or two? Determination of ring number in carotenoids by lycopene epsilon
      cyclases.
AB  - Carotenoids in the photosynthetic membranes of plants typically contain two beta
      rings (e.g., beta-carotene and zeaxanthin) or one epsilon- and one beta-ring
      (e.g., lutein). Carotenoids with two epsilon-rings are uncommon. We reported
      earlier that the Arabidopsis thaliana lycopene epsilon-cyclase (LCYe) adds one
      epsilon-ring to the symmetrical linear substrate lycopene, whereas the
      structurally related lycopene beta-cyclase (LCYb) adds two beta-rings. Here we
      describe a cDNA encoding LCYe in romaine lettuce (Lactuca sativa var. romaine),
      one of the few plant species known to accumulate substantial quantities of a
      carotenoid with two epsilon-rings: lactucaxanthin. The product of the lettuce
      cDNA, similar in sequence to the Arabidopsis LCYe (77% amino acid identity),
      efficiently converted lycopene into the bicyclic epsilon-carotene in a
      heterologous Escherichia coli system. Regions of the lettuce and Arabidopsis
      epsilon-cyclases involved in the determination of ring number were mapped by
      analysis of chimeric epsilon-cyclases constructed by using an inverse PCR
      approach. A single amino acid was found to act as a molecular switch: lettuce
      LCYe mutant H457L added only one epsilon-ring to lycopene, whereas the
      complementary Arabidopsis LCYe mutant, L448H, added two epsilon-rings. An R
      residue in this position also yields a bi-epsilon-cyclase for both the lettuce
      and Arabidopsis enzymes. Construction and analysis of chimera of related enzymes
      with differing catalytic activities provide an informative approach that may be
      of particular utility for studying membrane-associated enzymes that cannot easily
      be crystallized or modeled to existing crystal structures.

PMID- 11226340
TI  - Chlorophyll and carotenoid binding in a simple red algal light-harvesting complex
      crosses phylogenetic lines.
AB  - The membrane proteins of peripheral light-harvesting complexes (LHCs) bind
      chlorophylls and carotenoids and transfer energy to the reaction centers for
      photosynthesis. LHCs of chlorophytes, chromophytes, dinophytes, and rhodophytes
      are similar in that they have three transmembrane regions and several highly
      conserved Chl-binding residues. All LHCs bind Chl a, but in specific taxa certain
      characteristic pigments accompany Chl a: Chl b and lutein in chlorophytes, Chl c
      and fucoxanthin in chromophytes, Chl c and peridinin in dinophytes, and
      zeaxanthin in rhodophytes. The specificity of pigment binding was examined by in
      vitro reconstitution of various pigments with a simple light-harvesting protein
      (LHCaR1), from a red alga (Porphyridium cruentum), that normally has eight Chl a
      and four zeaxanthin molecules. The pigments typical of a chlorophyte (Spinacea
      oleracea), a chromophyte (Thallasiosira fluviatilis), and a dinophyte
      (Prorocentrum micans) were found to functionally bind to this protein as
      evidenced by their participation in energy transfer to Chl a, the terminal
      pigment. This is a demonstration of a functional relatedness of rhodophyte and
      higher plant LHCs. The results suggest that eight Chl-binding sites per
      polypeptide are an ancestral trait, and that the flexibility to bind various Chl
      and carotenoid pigments may have been retained throughout the evolution of LHCs.

PMID- 11226341
TI  - KAT1 is not essential for stomatal opening.
AB  - It is generally accepted that K(+) uptake into guard cells via inward-rectifying
      K(+) channels is required for stomatal opening. To test whether the guard cell
      K(+) channel KAT1 is essential for stomatal opening, a knockout mutant, KAT1En-1,
      was isolated from an En-1 mutagenized Arabidopsis thaliana population. Stomatal
      action and K(+) uptake, however, were not impaired in KAT1-deficient plants.
      Reverse transcription-PCR experiments with isolated guard cell protoplasts showed
      that in addition to KAT1, the K(+) channels AKT1, AKT2/3, AtKC1, and KAT2 were
      expressed in this cell type. In impalement measurements, intact guard cells
      exhibited inward-rectifying K(+) currents across the plasma membrane of both wild
      type and KAT1En-1 plants. This study demonstrates that multiple K(+) channel
      transcripts exist in guard cells and that KAT1 is not essential for stomatal
      action.

PMID- 11226342
TI  - Invariant scaling relationships for interspecific plant biomass production rates
      and body size.
AB  - The allometric relationships for plant annualized biomass production ("growth")
      rates, different measures of body size (dry weight and length), and
      photosynthetic biomass (or pigment concentration) per plant (or cell) are
      reported for multicellular and unicellular plants representing three algal phyla;
      aquatic ferns; aquatic and terrestrial herbaceous dicots; and arborescent
      monocots, dicots, and conifers. Annualized rates of growth G scale as the 3/4
      power of body mass M over 20 orders of magnitude of M (i.e., G proportional to
      M(3/4)); plant body length L (i.e., cell length or plant height) scales, on
      average, as the 1/4-power of M over 22 orders of magnitude of M (i.e., L
      proportional to M(1/4)); and photosynthetic biomass M(p) scales as the 3/4-power
      of nonphotosynthetic biomass M(n) (i.e., M(p)proportional to M(n)3/4). Because
      these scaling relationships are indifferent to phylogenetic affiliation and
      habitat, they have far-reaching ecological and evolutionary implications (e.g.,
      net primary productivity is predicted to be largely insensitive to community
      species composition or geological age).

PMID- 11226343
TI  - Metapopulation extinction caused by mutation accumulation.
AB  - Theory suggests that the risk of extinction by mutation accumulation can be
      comparable to that by environmental stochasticity for an isolated population
      smaller than a few thousand individuals. Here we show that metapopulation
      structure, habitat loss or fragmentation, and environmental stochasticity can be
      expected to greatly accelerate the accumulation of mildly deleterious mutations,
      lowering the genetic effective size to such a degree that even large
      metapopulations may be at risk of extinction. Because of mutation accumulation,
      viable metapopulations may need to be far larger and better connected than would
      be required under just stochastic demography.

PMID- 11226344
TI  - Lifespan depends on month of birth.
AB  - Month of birth influences adult life expectancy at ages 50+. Why? In two
      countries of the Northern Hemisphere-Austria and Denmark-people born in autumn
      (October-December) live longer than those born in spring (April-June). Data for
      Australia show that, in the Southern Hemisphere, the pattern is shifted by half a
      year. The lifespan pattern of British immigrants to Australia is similar to that
      of Austrians and Danes and significantly different from that of Australians.
      These findings are based on population data with more than a million observations
      and little or no selectivity. The differences in lifespan are independent of the
      seasonal distribution of deaths and the social differences in the seasonal
      distribution of births. In the Northern Hemisphere, the excess mortality in the
      first year of life of infants born in spring does not support the explanation of
      selective infant survival. Instead, remaining life expectancy at age 50 appears
      to depend on factors that arise in utero or early in infancy and that increase
      susceptibility to diseases later in life. This result is consistent with the
      finding that, at the turn of the last century, infants born in autumn had higher
      birth weights than those born in other seasons. Furthermore, differences in adult
      lifespan by month of birth decrease over time and are significantly smaller in
      more recent cohorts, which benefited from substantial improvements in maternal
      and infant health.

PMID- 11226345
TI  - The ethics of the cash register: taking tobacco research dollars.

PMID- 11226346
TI  - The strategy behind Florida's "truth" campaign.

PMID- 11226347
TI  - France : rolling round the curbs.

PMID- 11226350
TI  - USA: bad housekeeping.

PMID- 11226354
TI  - The Florida "truth" anti-tobacco media evaluation: design, first year results,
      and implications for planning future state media evaluations.
AB  - OBJECTIVES: To outline the design and present selected findings from the
      evaluation of a state counter-advertising, anti-tobacco media campaign. The
      appropriateness of the design for states developing media evaluations is
      discussed. DESIGN: Four cross sectional, telephone surveys of the 12--17 year old
      population were used to track and monitor advertising and campaign awareness,
      confirmed awareness, and receptivity. The Florida baseline and one year surveys
      were used with two parallel national surveys in a quasi-experimental design to
      assess attitude and smoking related behaviour change attributable to the
      campaign. MEASURES: Awareness was measured by self report, confirmed awareness by
      unaided description, and receptivity by self reports of how well advertisements
      were liked, talked to friends about, and made one think about whether or not to
      smoke. Eleven attitude and three smoking behaviour items for Florida (treatment)
      and a national (control) population were compared at baseline and after 12
      months. RESULTS: Significant increases in ad specific awareness, confirmed,
      receptivity, and campaign awareness, and confirmed awareness were reached by the
      sixth week. They continued to rise through the first year. No attitude and only
      minor behaviour differences were noted between the treatment and comparison
      populations at baseline. By the end of the first year, Florida youth had stronger
      anti-tobacco attitudes and better behaviour patterns than the comparison
      population. CONCLUSIONS: The industry manipulation strategy used in the Florida
      campaign resulted in high rates of recall, significant changes in
      attitudes/beliefs, and reduced rates of smoking behaviour among youth.

PMID- 11226355
TI  - Favourite movie stars, their tobacco use in contemporary movies, and its
      association with adolescent smoking.
AB  - OBJECTIVE: To assess the relation between adolescents' favourite movie stars, the
      portrayal of tobacco use by those stars in contemporary motion pictures, and
      adolescent smoking. DESIGN AND SETTING: 632 students (sixth to 12th grade, ages
      10-19 years) from five rural New England public schools completed a voluntary,
      self administered survey in October 1996. The survey assessed tobacco use, other
      variables associated with adolescent smoking, and favourite movie star. In
      addition, tobacco use by 43 selected movie stars was measured in films between
      1994 and 1996. OUTCOME MEASURES: Students were categorised into an ordinal five
      point index (tobacco status) based on their smoking behaviour and their smoking
      susceptibility: non-susceptible never smokers, susceptible never smokers, non
      current experimenters, current experimenters, and smokers. We determined the
      adjusted cumulative odds of having advanced smoking status based on the amount of
      on-screen tobacco use by their favourite film star. RESULTS: Of the 43 stars, 65%
      used tobacco at least once, and 42% portrayed smoking as an essential character
      trait in one or more films. Stars who smoked more than twice in a film were
      considered smokers. For adolescents whose favourite stars smoked in only one
      film, the odds of being higher on the smoking index was 0.78 (95% confidence
      interval (CI) 0.53 to 1.15). For adolescents whose favourite stars smoked in two
      films, the odds of being higher on the smoking index was 1.5 (95% CI 1.01 to
      2.32). For adolescents whose favourite stars smoked in three or more films
      (Leonardo DiCaprio, Sharon Stone, John Travolta), the odds of being higher on the
      smoking index was 3.1 (95% CI 1.34 to 7.12). Among never smokers (n = 281), those
      who chose stars who were smokers in three or more films were much more likely to
      have favourable attitudes toward smoking (adjusted odds ratio 16.2, 95% CI 2.3 to
      112). CONCLUSIONS: Adolescents who choose movie stars who use tobacco on-screen
      are significantly more likely to have an advanced smoking status and more
      favourable attitudes toward smoking than adolescents who choose non-smoking
      stars. This finding supports the proposition that the portrayal of tobacco use in
      contemporary motion pictures, particularly by stars who are admired by
      adolescents, contributes to adolescent smoking.

PMID- 11226357
TI  - Smoking cessation activities by general practitioners and practice nurses.
AB  - OBJECTIVES: To assess general practitioners' and practice nurses' self reported
      behaviour, attitudes, and knowledge in relation to smoking cessation. DESIGN AND
      SETTING: Two postal surveys of random national samples of 303 GPs (survey 1) and
      459 practice nurses (survey 2) covering England and Wales; effective response
      rates were 75% and 96%, respectively. RESULTS: Survey 1 found that 96% of GPs
      accepted that intervening against smoking was part of their role and almost all
      (99%) said that they recorded smoking status when patients registered; 57%
      reported that they routinely updated their records on smoking status, 50% said
      they advised smokers to stop during most or all consultations, and 76% said they
      advised smokers to cut down if they cannot stop. A large majority (83%) said they
      either recommended or prescribed nicotine replacement therapy (NRT). Although
      most GPs (86%) thought that NRTs were effective, only a minority thought they
      were worth the cost (47%) or should be on National Health Service (NHS)
      prescription (32%). There was little evidence that previous training in smoking
      cessation was associated with more activity, more positive attitudes, or greater
      knowledge. Survey 2 found that almost all practice nurses (99%) agreed that
      intervening against smoking was part of their role and 95% said they advised
      patients to stop at least occasionally; 71% said they advised smokers to stop at
      most or all consultations. A majority (74%) said that they recommended NRT to
      their patients. As with the GPs most practice nurses thought that nicotine
      replacement was effective (79%), but fewer (42%) thought the cost was justified,
      and only about half (53%) thought it should be available on NHS prescription.
      Nurses who said they had been trained in smoking cessation engaged in more
      activity relating to smoking cessation, had more positive attitudes, and were
      more knowledgeable. CONCLUSION: GPs and practice nurses accepted that intervening
      with smoking was an important part of their role and a large majority reported
      that they intervened at least with some smokers. This represents a promising
      baseline from which to proceed in terms of implementation of the new smoking
      cessation guidelines, but it is hoped that improvements can be made in terms of
      the frequency of updating records and intervening, and acceptance of the cost
      effectiveness of NRT as a life preserving intervention.

PMID- 11226356
TI  - A prescription for health: a primary care based intervention to maintain the non
      smoking status of young people.
AB  - OBJECTIVES: To evaluate the effectiveness of primary health care teams in
      maintaining a group of young people aged 10--15 years as non-smokers. DESIGN:
      Randomised controlled trial using postal questionnaires. SETTING: Oxfordshire,
      UK. SUBJECTS: 2942 young people who were initially self declared non-smokers.
      INTERVENTION: Information about smoking, sent under signature of the subject's
      general practitioner, certificates and posters intended to reinforce non-smoking
      behaviour. MAIN OUTCOME MEASURES: Changes in smoking behaviour, attitudes
      measured after one year. RESULTS: After a year, smoking uptake was 7.8% in the
      control group compared with 5.1% in the intervention group (odds ratio (OR) 1.6,
      95% confidence interval (CI) 1.1 to 2.2). Among boys the corresponding results
      were 5.2% and 2.4% (OR 2.3, 95% CI 1.2 to 4.6), and among girls 10.0% and 7.5%
      (OR 1.4, 95% CI 0.9 to 2.1). Among boys aged 14-15 the uptake rate was 12.8% in
      the control group compared with 5.4% in the intervention group. However, among
      girls of the same age the intervention was less effective, with smoking uptake of
      15.1% in the control group and 12.8% in the intervention group. The intervention
      was more effective among young people whose initial attitudes identified them as
      definite non-smokers than those who were potential smokers. CONCLUSIONS: The
      intervention substantially reduced smoking uptake among the young people,
      particularly boys. Primary health care teams can play an important role in
      maintaining the non-smoking status of their young patients. Confidential postal
      contact from the doctor direct to the young person at home is influential and
      cost-effective.

PMID- 11226358
TI  - Actual and perceived impacts of tobacco regulation on restaurants and firms.
AB  - OBJECTIVE: To examine the actual and anticipated costs of a law regulating
      workplace smoking and smoking in restaurants, taking into consideration observed
      and anticipated infrastructure costs, lost productivity, increased absenteeism,
      and loss of clientele. SETTING AND DESIGN: A survey of 401 Quebec restaurants and
      600 Quebec firms conducted by the Quebec Ministry of Health before the enactment
      of the law was used to derive costs incurred by those who had already complied
      and anticipated by those that did not. RESULTS: Direct and indirect costs
      associated with tobacco regulation at work and in restaurants were minimal.
      Annualised infrastructure costs amounted to less than 0.0002% of firm revenues
      and 0.15% of restaurant revenues. Anticipated costs were larger and amounted to
      0.0004% of firm revenues and 0.41% of restaurant revenues. Impacts on
      productivity, absenteeism, and restaurant patronage were widely anticipated but
      not observed in currently compliant establishments. CONCLUSION: Firms and
      restaurants expected high costs to result from strict tobacco regulation because
      of infrastructure costs, decreased productivity, and decreased patronage. That
      none of these were actually observed suggests that policy makers should discount
      industry claims that smoking regulations impose undue economic hardship.

PMID- 11226359
TI  - Smoking in correctional facilities: a survey of employees.
AB  - OBJECTIVE: To assess level of endorsement and expected consequences of worksite
      smoking restriction policies among correctional employees. DESIGN: Mailed survey
      to Vermont state correctional employees. MAIN OUTCOME MEASURES: Support for
      various policy alternatives for both staff and inmate smoking; expected
      consequences of restrictive smoking policies and smoking behaviour. PARTICIPANTS:
      321 of 640 (50%) state correctional employees responded. RESULTS: Employees were
      somewhat receptive to smoking restrictions for inmates, but less supportive of
      staff smoking restrictions. A complete ban on inmate smoking both indoors and
      outdoors was supported by 56% and 49% of never and ex-smokers, respectively, but
      only 15% of current smokers (p < 0.01). A similar ban on employee smoking was
      supported by 38% of never and ex-smokers, but only 3% of current smokers (p <
      0.01). Overall, employees were most supportive (52%) of a policy for themselves
      that banned indoor smoking and restricted it to certain areas outdoors. Current
      smokers were more likely to expect negative consequences as a result of further
      restrictions than were never or ex-smokers. CONCLUSIONS: Although our findings
      are limited by a low response rate, most employees support an indoor ban, but not
      a total ban on smoking. Employees generally favoured a policy that was slightly
      more restrictive than the current policy, but were less supportive of tighter
      smoking restrictions for themselves. However, a more restrictive smoking policy
      is likely to result in some degree of resistance among current smoking employees,
      who may require specific attention to address their opposition.

PMID- 11226360
TI  - The association of smoking and the cost of military training.
AB  - OBJECTIVE: To determine if premature discharge from the US Air Force was
      associated with the smoking status of recruits. DESIGN AND SETTING: A total of 29
      044 US Air Force personnel recruited from August 1995 to August 1996 were
      administered baseline behavioural risk assessment surveys during basic military
      training. They were tracked over a 12 month period to determine those who were
      prematurely discharged. MAIN OUTCOME MEASURES: Excess training costs as a result
      of premature discharge. RESULTS: In this 12 month period, 14.0% of those entering
      the US Air Force were discharged at a one year follow up. In both univariate and
      multivariate models, the best single predictor of early discharge was smoking
      status. Overall, 11.8% of non-smokers versus 19.4% of smokers were prematurely
      discharged (relative risk 1.795). CONCLUSIONS: Using US Department of Defense
      data on the cost of military training, recruits who smoke in the US Air Force are
      associated with $18 million per year in excess training costs. Applied to all
      service branches, smoking status, which represents a constellation of underlying
      behaviours and attitudes that can contribute to early discharge, is associated
      with over $130 million per year in excess training costs.

PMID- 11226361
TI  - Political economy of tobacco control in Thailand.
AB  - Thailand has some of the world's strongest anti-tobacco legislation. This paper
      examines the political economy of tobacco control in Thailand, emphasising the
      identification of forces which have supported and opposed the passage of strong
      anti-tobacco measures. It argues that while a powerful tobacco control coalition
      was created in the late 1980s, the gains won by this coalition are now under
      threat from systematic attempts by transnational tobacco companies to strengthen
      their share of the Thai cigarette market. The possible privatisation of the
      Thailand Tobacco Monopoly could threaten the tobacco control cause, but the pro
      control alliance is fighting back with a proposed Health Promotion Act which
      would challenge the tobacco industry with a hypothecated excise tax dedicated to
      health awareness campaigns.

PMID- 11226362
TI  - Development of the health and economic consequences of smoking interactive model.
AB  - OBJECTIVE: To describe the health and economic consequences of smoking model, a
      user friendly, web based tool, designed to estimate the health and economic
      outcomes associated with smoking and the benefits of smoking cessation. RESULTS:
      An overview of the development of the model equations and user interface is
      given, and data from the UK are presented as an example of the model outputs.
      These results show that a typical smoking cessation strategy costs approximately
      1200 pounds sterling per life year saved and 22,000 pounds sterling per death
      averted. CONCLUSIONS: The model successfully captures the complexity required to
      model smoking behaviour and associated mortality, morbidity, and health care
      costs. Furthermore, the interface provides the results in a simple and flexible
      way so as to be useful to a variety of audiences and to simulate a variety of
      smoking cessation methods.

PMID- 11226364
TI  - Tobacco control in an era of trade liberalisation.

PMID- 11226363
TI  - Why does smoking so often produce dependence? A somewhat different view.
AB  - The usual explanation for why smoking produces dependence focuses on the effects
      of nicotine on dopamine and other neurobiological explanations. This review
      offers four somewhat different explanations: (1) nicotine can offer several
      psychopharmacological benefits at the age when such benefits are especially
      needed; (2) cigarettes provide for a rapid, frequent, reliable and easy-to-obtain
      reward; (3) nicotine is not intoxicating, allowing chronic intake; and (4) the
      long duration of the nicotine withdrawal syndrome effectively undermines
      cessation. This article reviews the evidence for the above views and the tobacco
      control activities these views suggest.

PMID- 11226365
TI  - Why trade and investment liberalisation may threaten effective tobacco control
      efforts.

PMID- 11226366
TI  - Export "A" ads are extremely expert, eh?

PMID- 11226367
TI  - Big Tobacco is trying on the "Russian style".

PMID- 11226370
TI  - Prevalence and correlates of smoking on the roof of the world.
AB  - OBJECTIVE: To determine the prevalence and correlates of cigarette smoking among
      adults in high mountain rural areas of northern Pakistan. DESIGN: Cross sectional
      survey. PARTICIPANTS: A sample of 4203 adults (aged 18 years and over) were
      selected by stratified random sampling from 16 villages. MAIN OUTCOME MEASURE:
      Self reported smoking prevalence; age of smoking initiation; daily cigarette
      consumption and association between current smoking and sociodemographic
      variables, use of snuff, wine, body mass index, blood pressure, family history of
      stroke, and hypertension. RESULTS: 614/1406 men (43.7%) and 154/2797 (5.5%) women
      reported smoking cigarettes. The age standardised prevalence of smoking was 40.5%
      for men and 6.3% for women. Men were more likely (odds ratio (OR) 6.5, 95%
      confidence interval (CI) 4.75 to 8.79) to be smokers. Smokers were more likely to
      use snuff (OR 1.39, 95% CI 1.12 to 1.73), drink wine (OR 3.47, 95% CI 2.81 to
      4.29), and were more likely to work as farmers (OR 1.55, 95% CI 1.05 to 2.29) or
      shopkeepers (OR 2.63, 95% CI 1.67 to 4.14). Individuals with college level
      education and with desirable body mass index were less likely to smoke (OR 0.55,
      95% CI 0.35 to 0.87; OR 0.74, 95% CI 0.57 to 0.96). CONCLUSION: Cigarette smoking
      is a major public health problem in this high mountain community of Pakistan,
      particularly among the male population, the majority of whom begin to smoke quite
      early in life. A comprehensive tobacco control effort incorporated into the
      existing community based health infrastructure is needed.

PMID- 11226371
TI  - Role of Bcl-2 and its post-transcriptional modification in response to antitumor
      therapy.
AB  - Bcl-2 blocks or delays apoptosis in many cell systems. The protein exerts its
      antiapoptotic effect mainly in the membrane of mitochondria. Indeed, emerging
      evidence supports that the mitochondrion plays an important role in the cell
      death pathway, integrating different pro- and antiapoptotic stimuli. Since
      deregulation of the expression of Bcl-2 occurs in a variety of human tumors,
      modulation of its function is regarded as an exploitable manipulation for
      pharmacological intervention in antitumor chemotherapy. Phosphorylation of Bcl-2
      has been implicated as an important regulatory mechanism of its function and is a
      common event in response to antimitotic drugs. Recently, a similar post
      transcriptional modification was observed in response to DNA-damaging agents in
      some tumor systems, but this is not a general finding in response to genotoxic
      drugs. Current investigations indicate that different signaling pathways may be
      involved in Bcl-2 phosphorylation, likely dependent on the kinases activated by
      the various stress stimuli. A better understanding of the molecular mechanisms by
      which Bcl-2 regulates apoptosis could provide insights for a rational design of
      approaches to enhance the susceptibility to drug-induced cell death.

PMID- 11226372
TI  - Lack of toxic effects of F 12511, a novel potent inhibitor of acyl-coenzyme A:
      cholesterol O-acyltransferase, on human adrenocortical cells in culture.
AB  - Inhibition of acyl-coenzyme A: cholesterol O-acyltransferase (EC 2.3.1.26; ACAT)
      reduces intracellular cholesteryl esters that are substrates for steroidogenesis
      in adrenal cells. The adrenal side effects of ACAT inhibitors remain a key point
      for their development as antiatherosclerotic agents. The aim of this study was to
      characterize the effects of a novel and powerful ACAT inhibitor, F 12511 (S)
      2',3',5'-trimethyl-4'-hydroxy-alpha-dodecylthio-phenylacetanilide, on the NCI
      H295R cell line, which has functional properties comparable to those of normal
      human adrenal cells. F 12511 incubated with cultured cells for 4-72 hr strongly
      inhibited cholesteryl oleate formation. The concentrations required to produce
      50% inhibition (IC50) values) ranged from 20 to 50 nM; in the presence of low
      density lipoproteins (LDL), this effect was paralleled by a decrease in
      cholesteryl ester mass and an increase in intracellular free cholesterol. At
      concentrations 100-fold larger than the IC(50) value for up to 48 hr, F 12511
      reduced neither the basal release of cortisol and aldosterone nor the production
      of cortisol stimulated by forskolin. F 12511 did not modify the mRNA levels of
      the steroidogenic enzyme genes cytochrome P450 cholesterol side-chain cleavage
      (P450scc), cytochrome P450 17alpha-hydroxylase (P450c17), or cytochrome P450 21
      hydroxylase (P450c21) or those of the LDL receptor and high-density lipoprotein
      scavenger receptor class B, type I (SR-BI) genes, either in the presence or
      absence of adenosine 3',5'-cyclic monophosphate stimulation for 24 hr. Exposure
      to F 12511 at up to 3 microM for 24 or 48 hr did not result in significant change
      in morphological and ultrastructural characteristics; the cytoplasm contained
      large numbers of mitochondria with intact crystae, and the same typical features
      of secretory activity were observed in NCI-H295R control cells. Exposure to 3
      microM of F 12511 for 96 hr also did not affect cell viability. These data
      demonstrate that reduction of the substrate for steroidogenesis by the ACAT
      inhibitor F 12511 impairs neither steroid production nor transcription of genes
      involved in steroidogenesis and lipoprotein uptake in the pluripotent human
      adrenal cell line NCI-H295R.

PMID- 11226373
TI  - Induction of cytochrome P450 1A1 gene expression, oxidative stress, and
      genotoxicity by carbaryl and thiabendazole in transfected human HepG2 and
      lymphoblastoid cells.
AB  - Carbaryl and thiabendazole, two widely used pesticides, have been shown to induce
      cytochrome P450 1A1 (CYP1A1) expression, but neither compound is capable of
      displacing [3H] 2,3,7,8-tetrachlorodibenzo-P-dioxin from its aryl hydrocarbon
      receptor binding site. In the present study, we investigated the transcriptional
      regulation of CYP1A1 as well as other genes in various human hepatoma HepG2 cell
      lines stably transfected with the chloramphenicol acetyl transferase (CAT)
      reporter gene and cloned under the control of each of 14 promoters or response
      elements from relevant stress genes. Carbaryl and thiabendazole were found to
      activate CYP1A1 at the level of transcription, as demonstrated by the dose
      dependent increase in reporter CAT and CYP1A1 mRNAs. Moreover, this effect
      appeared to be mediated via the xenobiotic responsive element (XRE), because both
      pesticides specifically activated various fusion constructs containing XRE
      sequences (CYP1A, glutathione S-transferase, and XRE). Carbaryl and to a lesser
      extent thiabendazole also activated other stress genes such as c-fos and NF
      kappaBRE, HSP70 and GRP78, and GADD153 at a transcriptional level. These data
      suggest that these molecules induce early alert genes, including those known to
      be sensitive to oxidative stress. This led us to examine the genotoxic effect of
      carbaryl and thiabendazole by an in vitro DNA repair solid-phase assay. Both
      compounds provoked a strong DNA-damaging activity in the human lymphoblastoid
      cell line that constitutively expresses human CYP1A1 cDNA, but not in the
      parental line, indicating that CYP1A1 is chiefly implicated in carbaryl and
      thiabendazole genotoxicity. This effect was confirmed on HepG2 cells. These
      observations support the notion that intracellular signals leading to CYP1A1
      induction, oxidative stress, and genotoxicity are intimately related.

PMID- 11226375
TI  - Extracellular adenosine-induced apoptosis in mouse neuroblastoma cells: studies
      on involvement of adenosine receptors and adenosine uptake.
AB  - The induction of apoptosis by adenosine was studied in the mouse neuroblastoma
      cell line N1E-115. Apoptosis was characterized by fluorescence and electron
      microscopy, fluorescence-activated cell sorter (FACS) analysis, and caspase
      activity assays. A sixteen-hour exposure to 100 microM of adenosine led to
      chromatin condensation and caspase activation. However, selective agonists for
      all four adenosine receptors were ineffective. Caspase activation could be
      blocked partially by an inhibitor of the nucleoside transporter, dipyridamole,
      and completely by uridine, a competing substrate for adenosine transport. 2'
      Deoxycoformycin, an inhibitor of adenosine deaminase, enhanced caspase activation
      by adenosine but had no effect by itself. Caspase activation could be blocked by
      5'-amino-5'-deoxyadenosine, which inhibits the phosphorylation of adenosine by
      adenosine kinase. These results indicate that adenosine receptors are not
      involved in adenosine-induced apoptosis in N1E-115 cells, but that uptake of
      adenosine and its subsequent phosphorylation is required.

PMID- 11226374
TI  - The role of glutathione in the neurotoxicity of artemisinin derivatives in vitro.
AB  - The role of antioxidants in the neurotoxicity of the antimalarial endoperoxides
      artemether and dihydroartemisinin was studied in vitro by quantitative image
      analysis of neurite outgrowth in the neuroblastoma cell line NB2a. Intracellular
      glutathione concentrations were measured by high performance liquid
      chromatography with fluorescence detection. Both dihydroartemisinin (1 microM)
      and a combination of artemether (0.3 microM) plus haemin (2 microM) significantly
      inhibited neurite outgrowth from differentiating NB2a cells to 11.5 +/- 11.0%
      (SD) and 19.6 +/- 15.2% of controls, respectively. The inhibition by
      artemether/haemin was prevented by the antioxidants superoxide dismutase (109.7
      +/- 47.8% of control), catalase (107.0 +/- 29.3%) glutathione (123.8 +/- 12.4%),
      L-cysteine (88.0 +/- 6.3%), N-acetyl-L-cysteine (107.8 +/- 14.9%), and ascorbic
      acid (104.3 +/- 12.7%). Dihydroartemisinin-induced neurotoxicity was completely
      or partially prevented by L-cysteine (99.5 +/- 17.7% of control), glutathione
      (57.9 +/- 23.4% of control), and N-acetyl-L-cysteine (57.3 +/- 9.5%), but was not
      prevented by superoxide dismutase, catalase, or ascorbic acid. Buthionine
      sulphoximine, an inhibitor of gamma-glutamylcysteine synthetase, significantly
      increased the neurotoxic effect of non-toxic concentrations of artemether/haemin
      (0.1 microM/2 microM) and dihydroartemisinin (0.2 microM), suggesting that
      endogenous glutathione participates in the prevention of the neurotoxicity of
      artemether/haemin and dihydroartemisinin. Artemether/haemin completely depleted
      intracellular glutathione levels, whereas dihydroartemisinin had no effect. We
      conclude that although glutathione status is an important determinant in the
      neurotoxicity of endoperoxides, depletion of glutathione is not a prerequisite
      for their toxicity. This is consistent with their mechanisms of toxicity being
      free radical-mediated damage to redox-sensitive proteins essential for neurite
      outgrowth, or alteration of a redox-sensitive signalling system which regulates
      neurite outgrowth.

PMID- 11226376
TI  - Induction of cell proliferation by cyclosporine A in primary cultures of rat
      hepatocytes.
AB  - Cyclosporine A (CsA) has been reported to be able to promote cell proliferation,
      although the precise mechanism by which CsA stimulates cell growth remains
      uncertain. In the present study, we examined, in hepatocyte cultures, the effect
      of CsA on parameters related to the cell cycle as well as the levels of proteins
      involved in the control and progression of the cycle. Flow cytometry analysis
      detected an increase in the percentage of cells involved in the S phase of the
      cycle, which correlated with increases in the levels of cyclins D1 and E (two G1
      progression regulators), as well as in those of PCNA (proliferating cell nuclear
      antigen), and without modification in p27, an inhibitory protein of CDKs. We also
      examined in nucleus the levels of nuclear factor kappaB (a nuclear factor
      involved in the transcription of the cyclin D1 gene) and found that this
      transcription factor increased in the presence of CsA. We conclude that the
      increases in cyclin D1, PCNA, and cyclin E, together with the invariable level of
      p27, clearly show that CsA induces hepatocytes to proliferate. These results
      reinforce the idea of the growth-promoting effect of CsA in cultured hepatocytes.

PMID- 11226377
TI  - A functional link between heme oxygenase and cyclo-oxygenase activities in
      cortical rat astrocytes.
AB  - Recent evidence shows that the activation of heme oxygenase (HO) within the CNS
      is associated with increased prostanoid production. In this study, we
      investigated whether changes in HO activity induced by pharmacological
      manipulation are associated with parallel variations in cyclo-oxygenase (COX)
      activity and prostaglandin production in an in vitro paradigm of CNS cells, i.e.
      primary cultures of rat cortical astrocytes. Pharmacological tools commonly used
      to induce changes in HO activity, namely the HO enhancers hemin and CoCl(2) as
      well as the HO inhibitor Sn-mesoporphyrin-9 (SnMP9), were tested in our model,
      and the variations in COX activity associated with the above treatments were
      monitored by measuring a COX end product, prostaglandin E2 (PGE2), released into
      the incubation medium. We found that the increase in HO activity induced by hemin
      and/or CoCl(2) was not consistently associated with increases in prostaglandin
      production, whereas HO inhibition by SnMP9 was normally followed by a decrease in
      PGE2 release. The above effect was observed after both acute (30 min) and
      prolonged (24 hr) incubations, suggesting that baseline HO activity contributes
      to the maintenance of normal PG production in this model. Experiments with the
      stable HO end products biliverdin and bilirubin suggest that these products may
      play a role in mediating HO-induced COX activation.

PMID- 11226378
TI  - Comparison of the potency of adenosine as an agonist at human adenosine receptors
      expressed in Chinese hamster ovary cells.
AB  - The potency of adenosine and inosine as agonists at human adenosine receptors was
      examined in a functional assay using changes in cyclic AMP (cAMP) formation in
      intact Chinese hamster ovary (CHO) cells stably transfected with the human A1,
      A2A, A2B, and A3 receptors. Adenosine increased cAMP formation in cells
      expressing the A2A (EC(50): 0.7 microM) and A2B (EC(50): 24 microM) receptors and
      inhibited forskolin (0.3-3 microM)-stimulated cAMP formation in cells expressing
      the A1 (EC(50): 0.31 microM) and A3 receptors (EC(50): 0.29 microM). The potency
      of adenosine at the A2A and A2B receptors was not altered by the presence of the
      uptake inhibitor nitrobenzylthioinosine (NBMPR), whereas it was increased about 6
      fold by NBMPR at the A1 and A3 receptors. In the presence of NBMPR, inosine was a
      potent agonist (EC(50): 7 and 0.08 microM at the A1 and A3 receptors,
      respectively), but with low efficacy especially at the A3 receptors. No effect of
      inosine was seen at the A(2) receptors. Caffeine, theophylline, and paraxanthine
      shifted the dose-response curve for adenosine at the A1, A2A, and A2B receptors.
      These results indicate that adenosine is the endogenous agonist at all human
      adenosine receptors and that physiological levels of this nucleoside can activate
      A1, A2A, and A3 receptors on cells where they are abundantly expressed, whereas
      pathophysiological conditions are required to stimulate A2B receptors to produce
      cyclic AMP.

PMID- 11226379
TI  - In situ kinetic characterization of methylthioadenosine transport by the
      adenosine transporter (P2) of the African Trypanosoma brucei brucei and
      Trypanosoma brucei rhodesiense.
AB  - African trypanosomes are parasitic flagellates that live in the connective
      tissues of the host. Trypanosomes must obtain from their host adenine/adenosine
      and other nucleosides that can be salvaged through enzymatic cleavage.
      Methylthioadenosine (MTA) is a byproduct of polyamine metabolism, formed from the
      donation of an aminopropyl moiety by decarboxylated S-adenosylmethionine
      (dcAdoMet) to form spermidine. MTA is then cleaved phosphorolytically by MTA
      phosphorylase to methylthioribose-1-phosphate (MTR-1-P) and adenine. The uptake
      of MTA was compared with that of adenosine in two strains: Trypanosoma brucei
      brucei and Trypanosoma brucei rhodesiense. The K(m) values for MTA and adenosine
      (with 5 mM inosine) transport by T. b. brucei were 1.4 and 0.175 mM, and the
      V(max) values were 70 and 7.8 micromol/L/min, respectively. The K(m) values for
      T. b. rhodesiense MTA and adenosine (with 5 mM inosine) transport were 1.2 and
      0.11 mM, and the V(max) values were 52.6 and 2.9 micromol/L/min, respectively.
      Since MTA was not competitive with either AdoMet (100 microM), inosine (100
      microM), or the methionine precursor ketomethylthiobutyrate (100 microM), it
      appears that MTA enters through the P(2) (adenosine/adenine) transport site. From
      this study and our previous work, we determined that these organisms transport
      adenylated intermediates of methionine metabolism found in sera for purine
      salvage and as an ancillary source of methionine. The significant ability of
      African trypanosomes to transport MTA and related intermediates is an important
      consideration in the design and development of selective chemotherapeutic agents.

PMID- 11226380
TI  - Coupling of 5-fluoro 2'-deoxyuridine to lactosaminated poly-l-lysine: an approach
      to a regional, non-invasive chemotherapy of liver micrometastases.
AB  - Nucleoside analogs conjugated with galactosyl-terminating peptides selectively
      enter liver cells and after intracellular release from the carrier partly exit
      into bloodstream, resulting in higher concentrations in liver blood than in
      systemic circulation. The aim of the present experiments was to ascertain
      whether, in mice injected with non-toxic doses of a 5-fluoro 2'-deoxyuridine
      (FUdR) conjugate with lactosaminated poly-L-lysine (L-poly(LYS)), the drug was
      released by hepatic cells in high enough amounts to be pharmacologically active
      on neoplastic cells infiltrating the liver. We observed that L-poly(LYS)-FUdR
      inhibited the growth of hepatic metastases induced by intrasplenic administration
      of murine colon carcinoma C-26 cells. L-poly(LYS)-FUdR was not toxic for C-26
      cells in vitro, was selectively taken up by mouse liver, and was stable in mouse
      blood, indicating that the effect on the metastases was due to FUdR (and/or its
      active metabolites) released in liver blood after the conjugate was taken up by
      the hepatic cells. These results suggest that L-poly(LYS)-FUdR might be useful in
      adjuvant chemotherapy of tumors giving liver metastases. The drug released from
      hepatic cells into liver blood following conjugate administration via the
      peripheral venous route might accomplish a locoregional, non-invasive treatment
      of micrometastases nourished by liver sinusoids.

PMID- 11226382
TI  - Hypoxanthine transport in human tumour cell lines: relationship to the inhibition
      of hypoxanthine rescue by dipyridamole.
AB  - Hypoxanthine (HPX) uptake was investigated in four human tumour cell lines
      previously characterised as being sensitive (ds: A549 and MCF7) or insensitive
      (di: COR-L23 and T-47D) to dipyridamole (DP)-induced inhibition of HPX rescue
      from antipurine antifolate-induced growth inhibition. The aim of the study was to
      determine the mechanism underlying the differential sensitivity of HPX rescue to
      DP. The time-course of HPX uptake in the two ds cell lines was different in
      comparison to the two di cell lines. The initial rate of HPX uptake in the di
      cell lines was more rapid than in the ds cell lines such that at 60 sec the
      amount of HPX taken up by the former was 2-6 times higher than that taken up by
      the later. The K(t) and T(max) for HPX transport in di COR-L23 cells were 870
      microM and 4.75 microM/10(6) cells/min and 1390 microM and 1.78 microM/10(6)
      cells/min in ds A549 cells. HPX transport was not sodium-dependent in these
      cells. Equilibrative nucleoside transporter 2 (ENT2)-mediated thymidine transport
      was also higher in di cells. DP inhibited HPX uptake into ds cell lines by > or
      =48% and by < or =20% in the di cell lines. Competition studies with HPX and
      thymidine transport via ENT2 indicated an overlap between nucleoside and
      nucleobase transport transporters in the breast cancer cell lines (MCF7 and T
      47D). These studies showed that more rapid and extensive HPX uptake, as well as
      reduced sensitivity to DP inhibition, is associated with the inability of DP to
      prevent HPX rescue from antipurine antifolate-induced growth inhibition in
      certain human tumour cell lines.

PMID- 11226383
TI  - Lack of involvement of pertussis toxin-sensitive G-proteins in norepinephrine
      induced vasoconstriction of rat aorta smooth muscle.
AB  - Several studies have shown that stimulation of pertussis toxin (PTX)-sensitive G
      proteins amplified alpha-adrenoceptor (alpha-AR) agonist-induced vasoconstriction
      in small muscular and resistance arteries. The aim of this study was to assess
      the potential involvement of PTX-sensitive G-proteins in norepinephrine (NE)
      induced constriction in a large diameter artery, the rat aorta. PTX (1 microg/mL,
      2 hr; 3 microg/mL, 4 hr) did not modify concentration-response curves to NE in
      endothelium-denuded aortic rings. However, several lines of evidence suggested
      that aortic smooth muscle cells (SMC) had a PTX-sensitive G-protein pathway.
      [alpha-(32)P]ADP-ribosylation of G(i/o)-proteins by PTX (3 microg/mL, 4 hr) was
      demonstrated in situ in the intact aorta without endothelium. alpha(i/o) subunits
      were identified in vitro by both immunoblotting and ADP-ribosylation experiments
      in rat aorta SMC membranes. The measurement of G(i/o)-specific GTPase activity
      evidenced an effective coupling between NE receptors and G(i/o)-proteins, as NE
      induced an increase in basal G(i/o)-specific GTPase activity (20.7 +/- 2.8 vs 7.2
      +/- 2.2 pmol P(i)/mg protein at 5 min; P < 0.05 vs basal). Co-immunoprecipitation
      revealed the in vitro coupling between alpha(1D)-ARs and G(i)-protein in rat
      aorta SMC membranes. In conclusion, we identified a PTX-sensitive G(i/o)-protein
      pathway in rat endothelium-denuded aorta. We showed an effective coupling between
      NE receptors and G(i)-proteins via alpha(1D)-ARs. Since PTX has no effect on NE
      induced vasoconstriction, the PTX-sensitive G(i)-protein pathway does not play a
      predominant role in NE-induced responses in rat aorta SMC in contrast to small
      diameter muscular and resistance arteries.

PMID- 11226384
TI  - Cell-specific loss of cytochrome P450 2B1 in rat lung following treatment with
      pneumotoxic and non-pneumotoxic trialkylphosphorothioates.
AB  - This study was designed to test the hypothesis that the reduction in cytochrome
      P450 (CYP) 2B1 content and activity of rat lung microsomes, following dosing with
      pneumotoxic trimethylphosphorothioates, results from damage to specific cell
      types. Of the lung cells exhibiting immunolabelling for CYP2B1, only type I cells
      showed signs of susceptibility to the pneumotoxins O,O.S
      trimethylphosphorothioate and O,S,S-trimethylphosphorodithioate. While most type
      I cells became necrotic, type II and Clara cells showed no signs of injury,
      despite their gradual loss of CYP2B1, as detected by immunogold labelling. This
      loss of labelling was accompanied by a 75% reduction in the immunoreactive CYP2B1
      content and an 85% reduction in pentoxyresorufin O-dealkylase activity in lung
      microsomes. In contrast, the non-pneumotoxic analogue O,O,S
      trimethylphosphorodithioate, differing from O,O,S-trimethylphosphorothioate by
      only the presence of a P = S rather than a P = O moiety, caused an even more
      rapid fall in pulmonary pentoxyresorufin O-dealkylase activity, but only a slight
      reduction in the microsomal content of CYP2B1. The recovery of this activity
      began within 12 hr of dosing. O,O,S-Trimethylphosphorodithioate, which acts as a
      suicidal inhibitor of pulmonary CYP2B1, did not cause any detectable lung injury
      or increase in cell division. These results are consistent with the initial
      reduction in both enzyme content and activity caused by the P = O - containing
      pneumotoxins resulting, almost entirely, from death of type I cells. Subsequent
      reductions that occur long after clearance of the toxin may be exacerbated by the
      onset of mitosis in Clara and type II cells.

PMID- 11226381
TI  - Increased efficacy of antileishmanial antisense phosphorothioate oligonucleotides
      in Leishmania amazonensis overexpressing ribonuclease H.
AB  - Ribonuclease H (RNase H), an enzyme that cleaves an RNA sequence base-paired with
      a complementary DNA sequence, is proposed to be the mediator of antisense
      phosphorothioate oligonucleotide (S-oligo) lethality in a cell. To understand the
      role of RNase H in the killing of the parasitic protozoan Leishmania by antisense
      S-oligos, we expressed an episomal copy of the Trypanosoma brucei RNase H1 gene
      inside L. amazonensis promastigotes and amastigotes that constitutively express
      firefly luciferase. Our hypothesis was that S-oligo-directed degradation of
      target mRNA is facilitated in a cell that has higher RNase H activity. Increased
      inhibition of luciferase mRNA expression by anti-luciferase S-oligo and by anti
      miniexon S-oligo in these stably transfected promastigotes overexpressing RNase
      H1 was correlated to the higher activity of RNase H in these cells. The
      efficiency of killing of the RNase H overexpressing amastigotes inside L.
      amazonensis-infected macrophages by anti-miniexon S-oligo was higher than in the
      control cells. Thus, RNase H appears to play an important role in the antisense S
      oligo-mediated killing of Leishmania. Chemical modification of S-oligos that
      stimulate RNase H and/or co-treatment of cells with an activator of RNase H may
      be useful for developing an antisense approach against leishmaniasis. The
      transgenic Leishmania cells overexpressing RNase H should be a good model system
      for the antisense-mediated gene expression ablation studies in these parasites.

PMID- 11226385
TI  - Inhibition by ginkgolides and bilobalide of the production of nitric oxide in
      macrophages (THP-1) but not in endothelial cells (HUVEC).
AB  - Nitric oxide (NO) is a principal mediator in many physiological and pathological
      processes. NO produced by constitutive nitric oxide synthase in endothelial cells
      (eNOS) acts as a vasodilator, whereas excess NO production due to elevated
      expression of inducible nitric oxide synthase (iNOS) may produce cytotoxic
      effects to cells in the vascular wall. We demonstrated in our previous work that
      the extract of Ginkgo biloba leaves (EGb) inhibits iNOS-mediated NO production.
      The objective of the present study was to investigate the effects of several
      active EGb components on iNOS-mediated NO production in macrophages derived from
      a human monocytic cell line (THP-1), as well as on eNOS-mediated NO production in
      human umbilical vein endothelial cells (HUVEC). Ginkgolide A, ginkgolide B, or
      bilobalide (0.25 to 1.0 microg/mL) caused a 30-65% reduction in the levels of NO
      metabolites released by THP-1 macrophages after 4 hr of incubation, with a
      corresponding decrease in iNOS activity. Western immunoblotting analysis coupled
      with a nuclease protection assay and reverse transcription-polymerase chain
      reaction revealed a concomitant reduction in the levels of iNOS protein mass and
      mRNA in ginkgolide A-, ginkgolide B-, or bilobalide-treated macrophages. On the
      other hand, these compounds did not affect eNOS-mediated NO production or the
      expression of eNOS protein and mRNA in HUVEC. Taken together, these results
      suggest that ginkgolide A, ginkgolide B, and bilobalide may contribute to the
      selective inhibitory effect of EGb on iNOS expression without affecting eNOS
      mediated NO production.

PMID- 11226386
TI  - Transport of new non-cross-resistant antitumor compounds of the benzoperimidine
      family in multidrug resistant cells.
AB  - Multidrug resistance (MDR) phenotype in mammalian cells is often correlated with
      overexpression of P-glycoprotein or multidrug resistance-associated protein
      (MRP1). Both proteins are energy-dependent drug efflux pumps that efficiently
      reduce the intracellular accumulation and hence the cytotoxicity of many natural
      cytotoxins. The influx and efflux of drugs across the cell membrane are in large
      part responsible for their intracellular concentrations, and in the search for
      new compounds able to overcome MDR, it is of prime importance to determine the
      molecular parameters whose modification would lead to an increase in the kinetics
      of uptake and/or to a decrease in the pump-mediated efflux. Here, we studied
      three members of a new family of benzoperimidine antitumor compounds which
      exhibit comparable cytotoxicity towards resistant cells expressing P
      glycoprotein, or MRP1, and sensitive cells. We used spectrofluorometric methods
      to determine the kinetics of the uptake and release of these three drugs in
      different cell lines: the erythroleukemia cell line K562 and the resistant
      K562/Adr expressing P-glycoprotein, the small-cell lung cancer cell line GLC4 and
      resistant GLC4/Adr expressing MRP1. We also studied, using confocal microscopy,
      the intracellular distribution of these drugs in NIH/3T3 cells. Our data show
      that (i) the kinetics for the uptake of these drugs is very rapid, higher than 2
      x 10(-17) mole cell(-1) s(-1), (ii) the drugs are strongly accumulated in the
      nucleus and lysosomes, (iii) the three drugs are recognized and pumped out by
      both transporters, as shown by the inhibition of P-glycoprotein- and MRP1
      mediated efflux of pirarubicin by benzoperimidine, with inhibitory constants of
      1.5 and 2.1 microM for P-glycoprotein and MRP1, respectively, suggesting that
      benzoperimidine is transported by the two transporters with K(m) approximately 2
      microM. In conclusion, the fast uptake kinetics of the benzoperimidines
      counterbalance their efflux by P-glycoprotein and MRP1.

PMID- 11226387
TI  - Molecular and pharmacological characterization of the murine tachykinin NK(3)
      receptor.
AB  - Starting with a partial sequence from Genbank, polymerase chain reaction (PCR)
      was utilized to isolate the full-length cDNA for NK(3) receptor from mouse brain.
      The murine NK(3) receptor has a predicted sequence of 452 amino acids, sharing
      96% and 86% identity to the rat and human NK(3) receptors, respectively. Binding
      affinities and functional potencies of tachykinin receptor agonists were similar
      in HEK (human embryonic kidney) 293 cells expressing murine NK(3) receptor and
      human NK(3) receptor, although substance P and neurokinin A were more potent
      stimulators of Ca(2+) mobilization in murine NK(3) receptor cells. NK(3) receptor
      selective antagonists from two structural classes, had 10- to 100-fold lower
      binding affinities for murine NK(3) receptor compared to human NK(3) receptor,
      and about 5- to 10-fold reduced potency in the murine NK(3) receptor functional
      assay. The results demonstrate species differences in the potencies of tachykinin
      receptor antagonists in murine and human NK(3) receptors, and the lower potencies
      in the former should be taken into consideration when using murine disease
      models.

PMID- 11226389
TI  - Leukotriene D(4)-induced Rho-mediated actin reorganization in human bronchial
      smooth muscle cells.
AB  - We investigated the role of cysteinyl leukotriene (CysLT) receptors on
      leukotriene D(4)-induced actin reorganization and the signaling pathways of the
      response in human bronchial smooth muscle cells. The effects of leukotriene D(4)
      on actin reorganization in human bronchial smooth muscle cells were evaluated by
      dual-fluorescence labeling of filamentous (F) and monomeric (G) actin with
      fluorescein isothiocyanate (FITC)-labeled phalloidin and Texas Red-labeled DNase
      I, respectively. Leukotriene D(4) (100 nM) induced actin reorganization in the
      presence and absence of extracellular Ca(2+). The CysLT type 1 (CysLT(1))
      receptor antagonist ONO 1078 (4-oxo-8(-)[p-(4-phenylbutyloxy) benzoylamino]-2
      (tetrazol-5-yl)-4H-1-benzopyran hemihydrate) inhibited leukotriene D(4)-induced
      actin reorganization. Pretreatment with pertussis toxin, C3 exoenzyme, or
      tyrosine kinase inhibitors significantly reduced leukotriene D(4)-induced actin
      reorganization. However, phosphatidylinositol-3-kinase and protein kinase C
      inhibitors had little effect on these responses. These results suggest that
      leukotriene D(4)-induced actin reorganization in human bronchial smooth muscle
      cells is extremely dependent on the CysLT(1) receptor coupled with pertussis
      toxin-sensitive G protein, Rho GTPases and tyrosine phosphorylation pathways.

PMID- 11226388
TI  - Regulation of p42/p44 MAPK and p38 MAPK by the adenosine A(1) receptor in
      DDT(1)MF-2 cells.
AB  - The mitogen-activated protein kinase (MAPK) family consists of the p42/p44 MAPKs
      and the stress-activated protein kinases, c-Jun N-terminal kinase (JNK) and p38
      MAPK. We have previously reported that the human adenosine A(1) receptor
      stimulates p42/p44 MAPK in transfected Chinese hamster ovary cells. In this
      study, we have investigated whether the endogenous adenosine A(1) receptor in the
      smooth muscle cell line, DDT(1)MF-2 activates p42/p44 MAPK, JNK and p38 MAPK. The
      adenosine A(1) receptor agonist N(6)-cyclopentyladenosine stimulated time and
      concentration-dependent increases in p42/p44 MAPK and p38 MAPK phosphorylation in
      DDT(1)MF-2 cells. No increases in JNK phosphorylation were observed following
      adenosine A(1) receptor activation. N(6)-cyclopentyladenosine-mediated increases
      in p42/p44 MAPK and p38 MAPK phosphorylation were blocked by the selective
      adenosine A(1) receptor antagonist 1,3-dipropylcyclopentylxanthine and following
      pretreatment of cells with pertussis toxin. Furthermore, adenosine A(1) receptor
      mediated increases in p42/p44 MAPK were sensitive to the MAPK kinase 1 inhibitor
      PD 98059 (2'-amino-3'-methoxyflavone), whereas p38 MAPK responses were blocked by
      the p38 MAPK inhibitor SB 203580 (4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5
      (4-pyridyl)1H-imidazole). The broad range protein tyrosine kinase inhibitors
      genistein and tyrphostin A47 (alpha-cyano-(3,4-dihydroxy)thiocinnamide) did not
      block adenosine A(1) receptor stimulation of p42/p44 MAPK. For comparison,
      insulin-mediated increases in p42/p44 MAPK were blocked by genistein and
      tyrphostin A47. The Src tyrosine kinase inhibitor PP2 (4-amino-5-(4-chlorophenyl)
      7-(t-butyl)pyrazolo[3,4-d]pyrimidine) and the epidermal growth factor receptor
      tyrosine kinase inhibitor AG1478 (4-(3-chloroanilino)-6,7-dimethoxyquinazoline)
      also had no effect on adenosine A(1) receptor stimulation of p42/p44 MAPK.
      Furthermore, the protein kinase C inhibitors Ro 31-8220 (3-[1-[3-(2
      isothioureido) propyl]indol-3-yl]-4-(1-methylindol-3-yl)-3-pyrrolin-2,5-dione),
      chelerythrine and GF 109203X (2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H
      indol-3-yl)-maleimide) were without effect on adenosine A(1) receptor-induced
      p42/p44 MAPK phosphorylation. In contrast, wortmannin and LY 294002 (2-(4
      morpholinyl)-8-phenyl-4H-1-benzopyran-4-one), inhibitors of phosphatidylinositol
      3-kinase, attenuated adenosine A(1) receptor stimulation of p42/p44 MAPK
      phosphorylation. In conclusion, the adenosine A(1) receptor stimulates p42/p44
      MAPK through a pathway which appears to be independent of tyrosine kinase
      activation but involves phosphatidylinositol 3-kinase. Finally, adenosine A(1)
      receptor stimulation in DDT(1)MF-2 cells also activated p38 MAPK but not JNK via
      a pertussis toxin-sensitive pathway.

PMID- 11226390
TI  - Effects of spinorphin and tynorphin on synaptic transmission in rat hippocampal
      slices.
AB  - Spinorphin has been isolated from the bovine spinal cord as an endogenous
      inhibitor of enkephalin-degrading enzymes (aminopeptidase, dipeptidyl
      aminopeptidase III, angiotensin-converting enzyme and enkephalinase), and
      tynorphin has been synthesized as a more potent inhibitor of dipeptidyl
      aminopeptidase III. In this study, the effects of spinorphin and tynorphin on
      synaptic transmission were studied in rat isolated hippocampal slices. Field
      potentials were recorded from the CA1 region after stimulation of Schaffer
      collaterals. Spinorphin (1 microM), which alone had no effect, potentiated the
      facilitatory effects of enkephalin on the filed potentials at a stimulation
      interval of 15 s. At a stimulation interval of 10--4 s, spinorphin alone
      frequency dependently inhibited the field potential. On the other hand, tynorphin
      (1 microM), which alone had no effect at any stimulus interval, tended to
      potentiate the facilitatory effects of enkephalin. Spinorphin blocked long-term
      potentiation induced by tetanic stimulation (100 Hz, 1 s), whereas tynorphin had
      no effect on long-term potentiation. These results suggest that, at a low
      stimulation frequency, spinorphin potentiates the facilitatory effects of
      enkephalin by preventing degradation of enkephalin, whereas at a high stimulation
      frequency spinorphin use dependently inhibits synaptic transmission independently
      of enkephalin. On the other hand, tynorphin tends to potentiate the facilitatory
      effects of enkephalin without use-dependent inhibition.

PMID- 11226391
TI  - Characterisation of the prejunctional inhibitory muscarinic receptor on
      cholinergic nerves in the rat urinary bladder.
AB  - The nature of the prejunctional inhibitory muscarinic receptor on cholinergic
      nerve endings in the rat urinary bladder was investigated by measuring stimulated
      endogenous acetylcholine release via high pressure liquid chromatography (HPLC),
      in the presence of various selective muscarinic antagonists. The rank order of
      potencies for the antagonists used was: atropine (-log concentration = 7.8) > 4
      DAMP (4-diphenylacetoxy-N-methylpiperidine) (7.6) > tripitramine (7.3) = HHD
      (hexahydrodifenidol) (7.3) > pFHHSiD (p-fluoro-hexahydrosiladifenidol
      hydrochloride) (7.0) > himbacine (6.5) > methoctramine (5.9) > or = pirenzepine
      (5.8) > gallamine (4.3). A comparison of the antagonist potencies obtained, with
      affinity constants at muscarinic M(1) to M(5) receptors, suggests that the
      prejunctional inhibitory muscarinic receptor is of the M(4) receptor subtype.

PMID- 11226392
TI  - Changes in striatal electroencephalography and neurochemistry induced by kainic
      acid seizures are modified by dopamine receptor antagonists.
AB  - We investigated the involvement of striatal dopamine release in electrographic
      and motor seizure activity evoked by kainic acid in the guinea pig. The
      involvement of the dopamine receptor subtypes was studied by systemic
      administration of the dopamine D(1) receptor antagonist, R(+)-7-chloro-8-hydroxy
      3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH 23390;
      0.5 mg kg(-1)), or the dopamine D(2) antagonist, (5-aminosulphonyl)-N-[(1-ethyl-2
      pyrrolidinyl)-methyl]-2-methoxybenzamide (sulpiride, 30 mg kg(-1)). Microdialysis
      and high performance liquid chromatography were used to monitor changes in
      extracellular levels of striatal dopamine and its metabolites, glutamate,
      aspartate and gamma-amino-butyric acid (GABA). These data were correlated with
      changes in the striatal and cortical electroencephalographs and clinical signs.
      We found that, although neither dopamine receptor antagonist inhibited
      behavioural seizure activity, blockade of the dopamine D(1)-like receptor with
      SCH 23390 significantly reduced both the 'power' of the electrical seizure
      activity and the associated change in extracellular striatal concentration of
      glutamate, whilst increasing the extracellular striatal concentration of GABA. In
      contrast, blockade of the dopamine D(2)-like receptor with sulpiride
      significantly increased the extracellular, striatal content of glutamate and the
      dopamine metabolites. These results confirm previous evidence in other models of
      chemically-evoked seizures that antagonism of the dopamine D(1) receptor tends to
      reduce motor and electrographic seizure activity as well as excitatory amino-acid
      transmitter activity, while antagonism of the dopamine D(2) receptor has
      relatively less apparent effect.

PMID- 11226393
TI  - Sodium nitroprusside-induced seizures and adenosine release in rat hippocampus.
AB  - In the present study, we examined the effects of nitric oxide (NO)-related
      compounds, i.e. sodium nitroprusside (NO donor), diethyldithiocarbamate (NO
      trapper) and dithiothreitol (superoxide radical scavenger) on release of
      aspartate and adenosine from rat hippocampus using electrophysiological and
      microdialysis methods. Perfusion with 0.05 or 0.5 mM sodium nitroprusside
      significantly reduced high K(+)-evoked release of aspartate during high K(+)
      perfusion. Perfusion with 0.5 mM sodium nitroprusside always induced seizures and
      significantly increased release of aspartate and adenosine during washout of
      sodium nitroprusside. Diethyldithiocarbamate (5 mM) reversed the effects of
      sodium nitroprusside. Dithiothreitol (1 mM) significantly reduced the increase in
      adenosine release by sodium nitroprusside. These findings indicate that adenosine
      release is closely related to development of seizures, which are triggered by an
      increase in both NO itself and in part peroxynitrite, which results in reaction
      with superoxide radicals.

PMID- 11226394
TI  - Chronic GBR 12909 administration differentially alters prodynorphin gene
      expression compared to cocaine.
AB  - The effect of the selective dopamine uptake inhibitor 1-[2-[bis(4
      flourophenyl)methoxy]ethyl]-4-[3-phenylpropyl]piperazine dihydrochloride (GBR
      12909) was examined on prodynorphin gene expression. GBR 12909 or vehicle was
      continuously infused for 7 days via osmotic minipump, or injected daily into male
      rats. Both continuous infusions and daily injections of GBR 12909 produced
      significant decreases in prodynorphin expression in the hypothalamus (37% and 31%
      decreases, respectively). There were no significant changes in the caudate
      putamen, hippocampus or nucleus accumbens. One injection of GBR 12909 had no
      effects on prodynorphin expression in any of the brain regions studied,
      suggesting that the effect in the hypothalamus is not an acute effect. As
      previously reported for other treatment regimens, continuous infusion of cocaine
      produced a 35% significant decrease in the hypothalamus, consistent with the
      effects of GBR 12909. In contrast to GBR 12909, however, cocaine also produced a
      significant increase in prodynorphin expression in the caudate putamen. Thus,
      chronic inhibition of dopamine uptake can regulate prodynorphin expression in the
      hypothalamus. In contrast, the increase in the caudate putamen following cocaine
      administration may not be related to the inhibition of dopamine uptake, since it
      was not produced by a selective dopamine uptake inhibitor. These findings suggest
      that regulation of prodynorphin gene expression by cocaine in the caudate putamen
      may be mediated by the inhibition of norepinephrine or serotonin uptake, by a
      combination of effects on two or three monoamine transporters, or by a mechanism
      unrelated to transporter inhibition.

PMID- 11226395
TI  - Electroconvulsive shock increases tachykinin NK(1) receptors, but not the
      encoding mRNA, in rat cortex.
AB  - Recent studies have suggested that the substance P (tachykinin NK(1)) receptor
      may be a pharmacological target for the treatment of mood disorders. Here, the
      effects of electroconvulsive shock on tachykinin NK(1) receptor gene expression
      in the rat brain was investigated. Rats received either a single
      electroconvulsive shock or five shocks on alternate days. Quantitative
      autoradiography with [(125)I]Bolton Hunter-substance P, and in situ hybridisation
      histochemistry, were used to measure tachykinin NK(1) receptor-binding site
      densities and mRNA abundance, respectively. Densities of tachykinin NK(1)
      receptor-binding sites were significantly increased in the cerebral cortex
      following repeated electroconvulsive shock compared to sham treated animals.
      Densities remained unchanged in the hippocampus, striatum and amygdala. Neither
      single nor repeated electroconvulsive shock altered tachykinin NK(1) receptor
      mRNA in the brain regions examined. Hence, repeated electroconvulsive shock
      increases tachykinin NK(1) receptors in the rat brain in a regionally specific
      way. Upregulation of receptor-binding sites without a change in mRNA indicates
      that translational or post-translational mechanisms underlie this process.

PMID- 11226396
TI  - Dehydroevodiamine attenuates beta-amyloid peptide-induced amnesia in mice.
AB  - Dehydroevodiamine has been reported to have anticholinesterase activity and an
      anti-amnesic effect. This study examined the effects of dehydroevodiamine on
      scopolamine- and beta-amyloid peptide-(25--35)-induced amnesia in mice, using a
      step-through passive avoidance test. Similarly to the cholinesterase inhibitor,
      physostigmine (0.03--0.3 mg/kg, i.p.), dehydroevodiamine (0.75--12.0 mg/kg, i.p.)
      administered 30 min before the training trial, immediately after the training
      trial, and 30 min before the retention test significantly improved scopolamine-
      and beta-amyloid peptide-(25--35)-induced amnesia. In beta-amyloid peptide-(25-
      35)-induced amnesia, the rank order of anti-amnesic potency in these three
      administration schedules for dehydroevodiamine was different from that for
      physostigmine. Furthermore, dehydroevodiamine was more potent to improve beta
      amyloid peptide-(25--35)-induced amnesia than scopolamine-induced amnesia when
      administered before the training trial. These results suggested that
      dehydroevodiamine may have an action other than that of an anticholinesterase and
      may be a novel and effective ligand for improvement of beta-amyloid type amnesia.

PMID- 11226397
TI  - Intracerebral self-administration of the cannabinoid receptor agonist CP 55,940
      in the rat: interaction with the opioid system.
AB  - The effect of CP 55,940 [(-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans
      4-(3-hydroxypropyl)cyclo-hesanol], heroin and etonitazene on
      intracerebroventricular (i.c.v.) self-administration in a free-choice procedure
      was evaluated in rats. Animals were trained in 1-h daily sessions with a
      continuous reinforcement schedule to press two active levers to obtain the
      vehicle of each drug. Then, when a stable baseline was reached, each drug could
      be self-administered by pressing the lever found to be less preferred during
      training, while the vehicle came from the other. The number of bar pressings
      associated with the delivery of increasing unit doses of CP 55,940 (0.1, 0.2,
      0.4, 0.8, 1.6 microg/2 microl/infusion), heroin (0.125, 0.25, 0.5, 1, 2 microg/2
      microl/infusion) or etonitazene (0.1--0.2--0.5--1 microg/ 2 microl/infusion) and
      with the delivery of the corresponding vehicle was fitted by symmetrical
      parabolas. The mean drug intake was linearly related to the log of self
      administered drugs. Pretreatment with SR141716A [N-piperidino-5-(4-chlorophenyl)1
      (2,4-dichloro-phenyl)-4-methylpyrazole-3-carboxamide] (0.5 mg/kg) or naloxone HCl
      (2 mg/kg/i.p.) 15 min before each daily session reduced the self-administration
      of both CP 55,940 and heroin. The combination of CP 55,940 with heroin or
      etonitazene reduced the number of drug-associated lever pressings compared to
      that obtained with the maximal reinforcing unit dose of each drug alone. These
      findings suggest there may be a strong interaction between opioids and the
      cannabinoid system.

PMID- 11226398
TI  - Enhancement of memory consolidation in chicks by beta(3)-adrenoceptor agonists.
AB  - The effects of intracranial injection of three beta(3)-adrenoceptor agonists,
      sodium-4-[-2[-2-hydroxy-2-(-3-chloro-phenyl)ethylamino] propyl]phenoxyacetate
      (BRL 37344), 2-hydroxy-5(2-((2-hydroxy-3-(4-((1-methyl-4-trifluoromethyl)1H
      imidazole-2-yl)-phenoxy)propyl)amino)ethoxy)-benzamide monomethane sulfonate) (+/
      )-CGP12177A) and the pro-drug RS-N-(7-carbethoxymethoxyl 1,2,3,4-tetrahydronaphth
      2-yl)-2 hydroxy 2-(3-chlorophenyl)ethanamine (SR58611A), were examined on
      reinforcement of memory in day-old chicks. BRL37344 and CGP12177 facilitated
      memory, whereas SR58611A had no effect. The dose-response relationships of the
      beta(3)-adrenoceptor agonists were challenged with the selective beta(3)
      adrenoceptor antagonist 3-(2-ethylphenoxy)-1-[(1S)-1,2,3,4-tetrahydronapth-1
      ylamino]-2S-2-propanol oxalate (SR59230A) or the beta(2)-adrenoceptor antagonist
      (-)propranolol. BRL 37344 appeared to act predominantly at beta(3)-adrenoceptors
      at low doses and at beta(2)-adrenoceptors at higher doses. Facilitation of labile
      into long-term storage by beta(3)-adrenoceptor agonists appears to be a class
      action of these drugs.

PMID- 11226399
TI  - Acute administration of nicotine impairs the hypotensive responses to bradykinin
      in rats.
AB  - Nicotine may contribute to smoking-induced endothelial dysfunction because of its
      ability to impair endothelium-dependent vasodilatation. We investigated whether
      the acute administration of nicotine changes the hypotensive responses to
      bradykinin in rats. The effects of pre-treatment with losartan or enalapril on
      the nicotine-induced changes in the responses to bradykinin were also evaluated.
      In study 1, anesthetized rats were cannulated via carotid artery for the
      measurement of mean arterial pressure. Dose-response curves to bradykinin (0.1,
      0.4, 1.6, 6.4, 25 and 100 microg/kg) were generated before and 10 min after the
      injection of nicotine (200 microg/kg, i.v.) or saline. The individual dose
      response curves were fitted to a four-parameter logistic equation using the
      ALLFIT program, which provided an estimate of the maximal response (E(max)) and
      of the dose of bradykinin producing the half-maximal response (ED(50)). In study
      2, rats were pre-treated orally with losartan (10 mg/kg/day) or enalapril maleate
      (25 mg/kg/day) for 2 weeks. Control rats received tap water alone. After pre
      treatment, the rats were anesthetized and used as described in study 1. Nicotine
      decreased the E(max) (from 73.0+/-7.5 to 65.7+/-3.3 mm Hg; P<0.05) but did not
      affect the ED(50). In study 2, losartan or enalapril did not affect nicotine
      induced decrease in responses to bradykinin; E(max) decreased in both groups
      (from 68.7+/-6.3 to 62.8+/-4.2 mm Hg, and from 53.8+/-13.0 to 43.1+/-7.1 mm Hg,
      respectively; P<0.05) without significantly changing the ED(50). These results
      suggest that nicotine impairs the endothelium-dependent hypotensive responses to
      bradykinin. This effect is not influenced by inhibition of the angiotensin
      converting enzyme or by blockade of the angiotensin AT(1) receptors.

PMID- 11226400
TI  - Endothelin-1-induced potentiation of adrenergic responses in the rabbit pulmonary
      artery: role of thromboxane A(2).
AB  - To examine whether low concentrations of endothelin-1 potentiate the
      vasoconstrictor response to adrenergic stimulation, we recorded the isometric
      response of rings of rabbit pulmonary artery to electrical stimulation and
      noradrenaline. Endothelin-1 (10(-10) M) potentiated the contractions induced by
      electrical stimulation and noradrenaline. The endothelin ET(B) receptor
      antagonist (2,6-dimethylpiperidinecarbonyl-gamma-methyl-Leu-N(in)
      [Methoxycarbonyl]-D-Trp-D-Nle) (BQ-788, 10(-6) M), but not the endothelin ET(A)
      receptor antagonist cyclo(D-Asp-Pro-D-Val-Leu-D-TRP) (BQ-123, 10(-6) M),
      inhibited the potentiating effects of endothelin-1. Pretreatment with the
      cyclooxygenase inhibitor indomethacin, the thromboxane synthase inhibitor
      furegrelate and the thromboxane receptor antagonist [1S
      [1alpha,2alpha(Z),3alpha,4alpha]]-7-[3-[[[[(1-oxoheptyl)amino]acetyl]amino]
      methyl]-7-oxabicyclo-[2.2.1]hept-2-yl]-5-heptenoic acid (SQ-30741) (all at 10(-5)
      M) prevented the potentiation induced by endothelin-1 on adrenergic stimulation.
      The Ca(2+) channel antagonist nifedipine (10(-6) M) did not affect the
      potentiation induced by endothelin-1. The results indicate that endothelin-1
      potentiates the responses to electrical stimulation and noradrenaline by
      activating endothelin ET(B) receptors. This potentiation depends on the
      production of cyclooxygenase-generated factors, probably thromboxane A(2).

PMID- 11226401
TI  - Sympathetic control of nasal blood flow in the rat mediated by alpha(1)
      adrenoceptors.
AB  - Experiments were undertaken, using laser-Doppler flowmetry, to determine the
      nature of adrenoceptors mediating sympathetic nerve evoked nasal vasoconstrictor
      responses in anesthetized rats. Presence of sympathetic tone was confirmed by a
      large (330%) increase of nasal blood flow following section of the ipsilateral
      preganglionic cervical sympathetic nerve. Electrical nerve stimulation produced
      reproducible, frequency-related nasal vasoconstrictor responses with near maximal
      response, observed at less than 10 Hz. Evoked nasal vasoconstrictor responses
      were largely blocked with intravenous treatment with the non-selective alpha
      adrenoceptor antagonists, phentolamine (5 mg kg(-1)) and phenoxybenzamine (2 mg
      kg(-1)), as well as with the selective alpha(1)-adrenoceptor antagonist, prazosin
      (300 microg kg(-1)). alpha(2)-Adrenoceptor antagonism with rauwolscine (500
      microg kg(-1)) potentiated neurally evoked nasal vasoconstriction. Neither
      atropine (1 mg kg(-1)) nor propranolol (1 mg kg(-1)) altered the evoked
      responses. Rats with intact cervical sympathetic nerves responded to rauwolscine
      with a modest constriction. Subsequent prazosin administration produced an
      increase of nasal blood flow of approximately 275%. These results suggest that
      the nasal vasculature of the rat is under intense sympathetic tone and that the
      resulting neurogenic vasoconstriction is mediated exclusively by activation of
      alpha(1)-adrenoceptors.

PMID- 11226402
TI  - Postjunctional alpha(2C)-adrenoceptor contractility in human saphenous vein.
AB  - The postjunctional alpha(2)-adrenoceptor-mediated contractility was characterized
      in human saphenous vein derived from coronary artery bypass graft surgery. Human
      saphenous vein contracted to alpha(2)-adrenoceptor selective agonists BHT-920
      (5,6,7,8-Tetrahydro-6-(2-propenyl)-4H-thiazolo[4,5-d]azepin-2-amine
      dihydrochloride; pD(2)=6.7+/-0.1) and UK 14,304 (5-Bromo-6-(2-imidazolin-2
      ylamino)quinoxaline; pD(2)=7.2+/-0.1). BHT-920-induced contractions were
      inhibited by the alpha(2)-adrenoceptor antagonist yohimbine (17-Hydroxy-yohimban
      16-carboxylic acid methyl ester hydrochloride; pA(2)=8.7+/-0.5), but not by the
      alpha(1)-adrenoceptor antagonist prazosin (1-[4-Amino-6,7-dimethoxy-2
      quinazolinyl]-4-[2-furanylcarbonyl]-piperazine hydrochloride; 300 nM). In
      contrast, prazosin (pK(b)=7.9+/-0.2) potently antagonized contractions elicited
      by the alpha(1)-adrenoceptor agonist phenylephrine ((R)-3-Hydroxy-alpha
      [(methylamino)methyl] benzenemethanol hydrochloride; pD(2)=4.9+/-0.1), indicating
      that both alpha(2)- and alpha(1)-adrenoceptor evoke human saphenous vein
      contractions. Functional antagonist activity estimates (pA(2) or pK(b)) obtained
      for the alpha-adrenoceptor antagonists ARC 239 (2-[2-(4-(2
      Methoxyphenyl)piperazin-1-yl)ethyl]-4,4-dimethyl-1,3-(2H,4H)-isoquinolindione
      dihydrochloride), WB 4101 (2-(2,6-Dimethoxyphenoxyethyl)aminomethyl-1,4
      benzodioxane hydrochloride) and HV 723 (alpha-ethyl-3,4,5-trimethoxy-alpha-(3-((2
      (2-methoxyphenoxy) ethyl)amino)propyl)benzeneacetonitrile) against BHT-920
      induced human saphenous vein contractions were 7.0+/-0.6, 8.3+/-0.6 and 7.7+/
      0.3, respectively. The alpha(2)-adrenoceptor subtype affinities (pK(i)) obtained
      in recombinant human alpha(2A)-, alpha(2B)- and alpha(2C)-adrenoceptor
      competition binding assays were 8.6, 8.3 and 8.6 for yohimbine; 6.3, 8.4 and 7.0
      for ARC 239; 8.4, 7.5 and 8.4 for WB 4101 and 7.5, 7.4 and 7.9 for HV 723,
      respectively. Taken together, the binding and functional antagonist activity
      estimates obtained in these investigations indicate that alpha(2C)-adrenoceptor
      is the predominant postjunctional alpha(2)-adrenoceptor subtype in human
      saphenous vein.

PMID- 11226403
TI  - Thromboxane A(2) causes retarded clearance of aggregated protein in glomeruli of
      nephritic mice.
AB  - Recently, it has been demonstrated that the production of prostaglandins and
      thromboxane is increased in patients with chronic glomerulonephritis and lupus
      nephritis. We recently demonstrated that thromboxane A(2) delayed the clearance
      of heat-aggregated bovine serum albumin deposited in glomeruli. In the present
      study, we investigated the effect of thromboxane A(2) on the clearance of
      macromolecules in nephritic glomeruli. First, we attempted to clarify the
      conditions for the clearance of heat-aggregated bovine serum albumin in nephritic
      glomeruli, using glomeruli isolated from control and anti-glomerular basement
      membrane nephritic mice. Heat-aggregated bovine serum albumin was injected twice
      into each mouse. The glomeruli were then isolated and incubated in culture
      medium. The heat-aggregated bovine serum albumin content of control glomeruli
      gradually diminished with incubation time up to 24 h. The heat-aggregated bovine
      serum albumin content of nephritic glomeruli was 69% higher than that of control
      glomeruli at 24 h incubation. The production of thromboxane B(2) (the stable
      metabolite of thromboxane A(2)) in nephritic glomeruli showed about a sevenfold
      increase compared with control. DP-1904 [6-(1-imidazolylmethyl)-5,6,7,8
      tetrahydro-naphthalene-2-carboxylic acid hydrochloride], a thromboxane A(2)
      synthase inhibitor, and KT2-962 [sodium 3-(4-(4-chlorophenyl-butylsulfonamido)
      butyl)-6-isopropylazulene-1-sulfonate], a selective thromboxane A(2) receptor
      antagonist, significantly reduced the heat-aggregated bovine serum albumin
      content in nephritic glomeruli. Normal glomeruli treated with U-46619 [15S
      hydroxy-11a,9a-(epoxymethano)prosta-5Z,13E-dienoic acid], a stable analogue of
      thromboxane A(2), had significantly more heat-aggregated bovine serum albumin
      than control glomeruli. We next investigated whether thromboxane A(2) could
      affect the uptake/disposal of heat-aggregated bovine serum albumin by cultured
      rat mesangial cells. U-46619 significantly enhanced the uptake and inhibited the
      disposal of heat-aggregated bovine serum albumin by mesangial cells. Finally, we
      performed experiments to elucidate the role of the thromboxane A(2) receptor (TP
      receptor) in the clearance of heat-aggregated bovine serum albumin using TP
      deficient mice. The glomerular heat-aggregated bovine serum albumin content of TP
      receptor knockout [TP(-/-)] mice was lower than that of wild-type [WT(+/+)] mice.
      U-46619 dose dependently increased the uptake of heat-aggregated bovine serum
      albumin by mesangial cells in WT(+/+) mice, but not in the TP(-/-) mice. These
      findings suggest that thromboxane A(2) retards the clearance of aggregated
      protein in nephritic glomeruli and may contribute to the pathophysiology of
      glomerulonephritis.

PMID- 11226404
TI  - The involvement of phospholipase A(2) in ethanol-induced gastric muscle
      contraction.
AB  - To understand the underlying mechanism of ethanol in tonic contraction, the
      effect of ethanol on phospholipase A(2) and phospholipase C activities and the
      effects of phospholipase inhibitors on ethanol-induced contraction of cat gastric
      smooth muscle were tested. Circular muscle strips (2.0 x 0.2 cm) obtained from
      the fundus of cat stomach were used to measure isometric contraction. Ethanol
      elicited tonic contraction and activated phospholipase A(2) activity in a dose
      dependent manner. Phospholipase A(2) inhibitors, manoalide (0.1--10 microM) and
      oleyloxyethyl phosphorylcholine (1--10 microM), significantly inhibited ethanol
      induced contraction. Furthermore, 342 mM ethanol-induced contraction was
      significantly inhibited by cyclooxygenase inhibitors, ibuprofen (10--100 microM)
      and indomethacin (10--100 microM), but not by lipoxygenase inhibitors. On the
      other hand, phospholipase C inhibitors had no effect on ethanol-induced
      contraction, indicating that phospholipase C is not involved in ethanol-induced
      contraction. It is suggested from the above results that ethanol-induced
      contraction in cat gastric smooth muscle is, in part, mediated by phospholipase
      A(2) and cyclooxygenase pathways.

PMID- 11226405
TI  - Influence of phenobarbital on changes in Na(+) handling, hemodynamics and liver
      function due to partial portal vein ligation in rats.
AB  - This study examined the influence of phenobarbital, an inducer of hepatic
      enzymes, on Na(+) handling, hemodynamics and liver function (measured by the rate
      constant of elimination of aminopyrine in the aminopyrine breath test) after
      partial portal vein ligation. Rats were randomized to drink either phenobarbital
      + water or water only for 10 days and then underwent either sham operation or
      partial portal vein ligation. The aminopyrine rate constant of elimination and
      Na(+) balance were measured daily before and after surgery; after surgery,
      hemodynamic measurements were obtained daily in a subset of rats. Phenobarbital
      raised the baseline aminopyrine rate constant of elimination. Partial portal vein
      ligation, but not sham operation, caused equivalent reductions in the aminopyrine
      rate constant of elimination in phenobarbital- and water-treated groups, such
      that the aminopyrine rate constant of elimination remained higher in the former.
      Na(+) balance increased significantly in partial portal vein ligation + water,
      but not sham + water rats on day 1 and then decreased on days 2 and 3. In
      contrast, neither sham + phenobarbital nor partial portal vein ligation +
      phenobarbital rats had a significant increase in Na(+) balance. Partial portal
      vein ligation resulted in vasodilation on day 3 after surgery in the water
      treated rats, an effect that was prevented by treatment with phenobarbital. These
      results support previous suggestions that a reduction in liver function triggers
      renal Na(+) retention in this model. Vasodilation is not necessary for the latter
      effect, but also appears to be dependent on a reduction in liver function.

PMID- 11226406
TI  - Use of protein kinase C inhibitors results in rapid [Mg(2+)](i) mobilization in
      primary cultured rat aortic smooth muscle cells: are certain kinase C isoforms
      natural homeostatic regulators of cystolic free Mg(2+).
AB  - The effects of five different protein kinase C inhibitors--calphostin C,
      chelerythrine, bisindolylmaleimide I, staurosporine and Go6979--on intracellular
      free magnesium ([Mg(2+)](i)) content and mobilization were investigated in
      primary, cultured rat aortic smooth muscle cells. All these protein kinase C
      inhibitors significantly and rapidly increased [Mg(2+)](i) both in normal media
      (1.2 mM Mg(2+)) and in Mg(2+) free media. These data suggest that the increments
      of [Mg(2+)](i), induced by the diverse protein kinase C inhibitors, are derived
      from the release of bound intracellular Mg(2+) and that activation of protein
      kinase C isozymes are normally responsible for helping to maintain basal levels
      of [Mg(2+)](i) in rat aortic smooth muscle cells.

PMID- 11226407
TI  - EGF receptor: which way to go?

PMID- 11226408
TI  - Localization of phospholipase C-gamma1 signaling in caveolae: importance in EGF
      induced phosphoinositide hydrolysis but not in tyrosine phosphorylation.
AB  - Upon epidermal growth factor treatment, phospholipase C-gamma1 (PLC-gamma1)
      translocates from cytosol to membrane where it is phosphorylated at tyrosine
      residues. Caveolae are small plasma membrane invaginations whose structural
      protein is caveolin. In this study, we show that the translocation of PLC-gamma1
      and its tyrosine phosphorylation are localized in caveolae by caveolin-enriched
      low-density membrane (CM) preparation and immunostaining of cells. Pretreatment
      of cells with methyl-beta-cyclodextrin (MbetaCD), a chemical disrupting caveolae
      structure, inhibits the translocation of PLC-gamma1 to CM as well as
      phosphatidylinositol (PtdIns) turnover. However, MbetaCD shows no effect on
      tyrosine phosphorylation level of PLC-gamma1. Our findings suggest that, for
      proper signaling, PLC-gamma1 phosphorylation has to occur at PtdInsP(2)-enriched
      sites.

PMID- 11226409
TI  - Epidermal growth factor receptor induced apoptosis: potentiation by inhibition of
      Ras signaling.
AB  - Previous studies have shown that certain tumor cell lines which naturally express
      high levels of the epidermal growth factor receptor (EGFR) undergo apoptosis when
      exposed to epidermal growth factor. Whether this phenomenon is a direct result of
      receptor overexpression or some other genetic alteration renders these cells
      sensitive to apoptosis is yet to be established. We show that experimentally
      increasing the level of EGFR expression predictably leads to apoptosis in a
      variety of cell types which requires an active tyrosine kinase but not EGFR
      autophosphorylation sites. Expression of a dominant negative Ras mutant in EGFR
      overexpressing cells results in a significant potentiation of EGFR induced
      apoptosis suggesting that Ras activation is a key survival signal generated by
      the EGFR. We propose that potentiation of EGFR induced apoptosis by dominant
      negative Ras results, at least in part, by a block of Akt activation.

PMID- 11226410
TI  - Proteolytic cleavage of epidermal growth factor receptor by caspases.
AB  - Apoptotic proteases cleave and inactivate survival signaling molecules such as
      Akt/PKB, phospholipase C (PLC)-gamma1, and Bcl-2. We have found that treatment of
      A431 cells with tumor necrosis factor-alpha in the presence of cycloheximide
      resulted in the cleavage of epidermal growth factor receptor (EGFR) as well as
      the activation of caspase-3. Among various caspases, caspase-1, caspase-3 and
      caspase-7 were most potent in the cleavage of EGFR in vitro. Proteolytic cleavage
      of EGFR was inhibited by both YVAD-cmk and DEVD-fmk in vitro. We also
      investigated the effect of caspase-dependent cleavage of EGFR upon the mediation
      of signals to downstream signaling molecules such as PLC-gamma1. Cleavage of EGFR
      by caspase-3 significantly impaired the tyrosine phosphorylation of PLC-gamma1 in
      vitro. Given these results, we suggest that apoptotic protease specifically
      cleaves and inactivates EGFR, which plays crucial roles in anti-apoptotic
      signaling, to abrogate the activation of EGFR-dependent downstream survival
      signaling molecules.

PMID- 11226411
TI  - Cytomegalovirus infection increases the expression and activity of ecto-ATPase
      (CD39) and ecto-5'nucleotidase (CD73) on endothelial cells.
AB  - We describe enhanced expression and enzymatic activity of ecto-ATPase and ecto
      5'nucleotidase on CMV infected endothelial cells as compared to uninfected cells.
      These ectoenzymes play a major role in modulation of platelet activation and
      aggregation. Furthermore, adenosine has a modulatory effect upon inflammation.
      Addition of ATP, ADP or AMP to cultures of CMV infected or uninfected endothelial
      cells revealed increased turnover of AMP in CMV infected endothelial cells. In
      addition, the superoxide production by stimulated polymorphonuclear cells was
      inhibited in the presence of CMV infected endothelial cells as compared to
      uninfected cells, probably due to the enhanced activity of ecto-5'nucleotidase
      and associated to production of adenosine.

PMID- 11226412
TI  - Structure of the ExoS GTPase activating domain.
AB  - Pseudomonas aeruginosa is an opportunistic bacterial pathogen of great medical
      relevance. One of its major toxins, exoenzyme S (ExoS), is a dual function
      protein with a C-terminal Ras-ADP-ribosylation domain and an N-terminal GTPase
      activating protein (GAP) domain specific for Rho-family proteins. We report here
      the three-dimensional structure of the N-terminal domain of ExoS determined by X
      ray crystallography to 2.4 A resolution. Its fold is all helical with a four
      helix bundle core capped by additional irregular helices. Loops that are known to
      interact with Rho-family proteins show very large mobility. Considering the
      importance of ExoS in Pseudomonas pathogenicity, this structure could be of
      interest for drug targeting.

PMID- 11226413
TI  - Involvement of histone H4 gene transcription factor 1 in downregulation of
      vimentin gene expression during skeletal muscle differentiation.
AB  - Upon in vitro myogenesis, the intermediate filament protein vimentin is replaced
      by desmin, the switch in gene expression occurring essentially at the
      transcriptional level. Trying to elucidate the molecular mechanisms of this
      genetic control, we show here that the vimentin promoter is specifically
      recognized and activated by a protein most probably identical to H4TF-1, and that
      this factor is present in proliferating myoblasts but disappears upon fusion of
      these cells into multinucleated myotubes. Our results suggest that H4TF-1 is a
      differentiation stage-specific factor involved in the downregulation of vimentin
      gene expression during myogenesis.

PMID- 11226414
TI  - Genetic determinants of homocysteine thiolactonase activity in humans:
      implications for atherosclerosis.
AB  - A metabolite of homocysteine (Hcy), the thioester Hcy thiolactone, damages
      proteins by modifying their lysine residues which may underlie Hcy-associated
      cardiovascular disease in humans. A protein component of high density
      lipoprotein, Hcy thiolactonase (HTase) hydrolyzes thiolactone to Hcy.
      Thiolactonase is a product of the polymorphic PON1 gene, also involved in
      detoxification of organophospates and implicated in cardiovascular disease.
      Polymorphism in PON1 affects the detoxifying activity of PON1 in a substrate
      dependent manner. However, how PON1 polymorphism affects HTase activity is
      unknown. Here we report a strong association between the thiolactonase activity
      and PON1 genotype in human populations. High thiolactonase activity was
      associated with L55 and R192 alleles, more frequent in blacks than in whites. Low
      thiolactonase activity was associated with M55 and Q192 alleles, more frequent in
      whites than in blacks. High thiolactonase activity afforded better protection
      against protein homocysteinylation than low thiolactonase activity. These results
      suggest that variations in HTase may play a role in Hcy-associated cardiovascular
      disease.

PMID- 11226415
TI  - c-IAP2 is induced by ionizing radiation through NF-kappaB binding sites.
AB  - Transcriptional promoters responsive to low doses of X-irradiation may be useful
      in developing a new strategy in gene therapy combined with conventional
      radiotherapy. The retrovirus-mediated gene trap screening identified c-IAP2 as
      one of genes possessing such promoters. The analysis of the cis-elements
      responsive to X-irradiation in c-IAP2 promoter revealed that the NF-kappaB
      binding sites were necessary and sufficient for the X-ray-responsiveness. We
      constructed the plasmid p4NFB-BAX, which had four tandem repeats of the NF-kappaB
      binding sites of c-IAP2 promoter (4NFB) and a suicide gene BAX under the control
      of 4NFB. The human tumor cells transfected with p4NFB-BAX significantly reduced
      the number of cells that survived 2 Gy irradiation.

PMID- 11226416
TI  - Activation of ion-conducting pathways in the inner mitochondrial membrane - an
      unrecognized activity of fatty acid?
AB  - The effect of non-esterified myristate (C14:0) or dodecyl sulfate was studied on
      passive swelling of rat liver mitochondria suspended in hypotonic alkaline KCl
      medium in the absence of the potassium ionophore valinomycin. Both compounds
      rapidly initiated large-amplitude swelling. However, they failed to initiate
      swelling when the mitochondria were suspended in hypotonic alkaline sucrose
      medium. In contrast to myristate or dodecyl sulfate, the non-ionic detergent
      Triton X-100 initiated swelling of mitochondria in both of the media. The
      following findings indicate that the inner mitochondrial membrane (IMM) is
      permeabilized by myristate to K+ and Cl- in a specific manner. (i) Swelling
      initiated by myristate did not respond to cyclosporin A, (ii) the protonophoric
      uncoupler FCCP was unable to mimic the myristate effect on swelling, and (iii)
      myristate-induced Cl- -permeation (measured with KCl medium plus valinomycin) was
      inhibited by N,N'-dicyclohexylcarbodiimide, quinine or ATP. Myristate- or dodecyl
      sulfate-initiated swelling was paralleled by the lowering of endogenous Mg2+
      content. Both effects, stimulation of swelling and depletion of endogenous Mg2+
      are correlated with each other. Similar effects have been reported previously for
      the carboxylic divalent cation ionophore calcimycin (A23187). The A23187-induced
      swelling has identical inhibiting characteristics on Cl- -permeation with respect
      to N,N'-dicyclohexylcarbodiimide, quinine and ATP as the myristate-stimulated
      swelling. Therefore, we conclude that non-esterified fatty acids increase the
      permeability of mitochondria to K+ and Cl- at alkaline pH by activating Mg2+
      dependent ion-conducting pathways in IMM.

PMID- 11226418
TI  - Dopamine beta-hydroxylase inactivation generates a protein-bound quinone
      derivative.
AB  - Bovine dopamine beta-hydroxylase (DbH) was inactivated by hydrogen peroxide and
      ascorbate in the presence of dioxygen. Both inactivated forms of the enzyme were
      investigated. We could highlight the presence of a quinone derivative bound to
      the protein, assumed as being dopa-quinone, that is absent from active enzyme.
      Such results suggest that a tyrosinyl radical transiently forms during catalysis.
      Moreover we could show that addition of substrate tyramine to H2O2 incubates is
      responsible for a partial protection of DbH against inactivation.

PMID- 11226417
TI  - Regulation of the activity of branched-chain 2-oxo acid dehydrogenase (BCODH)
      complex by binding BCODH kinase.
AB  - Branched-chain 2-oxo acid dehydrogenase (BCODH) kinase is responsible for
      inactivation of BCODH complex by phosphorylation of the complex. Activity of the
      kinase towards its substrate, the E1 component of the BCODH complex, is known
      dependent upon binding of the kinase to the E2 component. The possible existence
      as well as importance of unbound mitochondrial BCODH kinase has been largely
      ignored in previous studies. Evidence is presented here for the existence of free
      and bound BCODH kinase in the matrix space of rat liver mitochondria.
      Furthermore, in female rats, in which diurnal variations in liver BCODH complex
      and kinase activities occur, the amount of the kinase bound to the complex
      changes between morning and evening without a change in total kinase protein.
      Activity of the kinase correlates with the amount of bound rather than total
      kinase protein, suggesting only the bound form is active. Changes in amount of
      kinase bound and therefore active appear responsible for diurnal variation in
      BCODH complex activity in the female rat. We propose that change in the amount of
      bound BCODH kinase is a key feature of a novel regulatory mechanism for
      determining the activity state of the BCODH complex.

PMID- 11226419
TI  - Overexpression of endonuclease III protects Escherichia coli mutants defective in
      alkylation repair against lethal effects of methylmethanesulphonate.
AB  - Endonuclease III of Escherichia coli is normally involved in the repair of
      oxidative DNA damage. Here, we have investigated a possible role of EndoIII in
      the repair of alkylation damage because of its structural similarity to the
      alkylation repair enzyme 3-methyladenine DNA glycosylase II. It was found that
      overproduction of EndoIII partially relieved the alkylation sensitivity of alkA
      mutant cells. Site-directed mutagenesis to make the active site of EndoIII more
      similar to AlkA (K120W) had an adverse effect on the complementation and the
      mutant protein apparently inhibited repair by competing for the substrate without
      base release. These results suggest that EndoIII might replace AlkA in some
      aspect of alkylation repair, although high expression levels are needed to
      produce this effect.

PMID- 11226420
TI  - In vivo glycosylation suppresses the aggregation of amyloidogenic hen egg white
      lysozymes expressed in yeast.
AB  - The mutant hen egg white lysozymes Ile55Thr and Asp66His, corresponding to human
      amyloidogenic mutant lysozymes Ile56Thr and Asp67His, respectively, were secreted
      in Saccharomyces cerevisiae. The amyloidogenic mutants (I55T and D66H) of hen egg
      white lysozymes were remarkably less soluble than that of the wild-type protein.
      To enhance the secretion of these mutants, we constructed the glycosylated
      amyloidogenic lysozymes (I55T/G49N and D66H/G49N) having the N-glycosylation
      signal sequence (Asn-X-Ser) by the substitution of glycine with asparagine at
      position 49. The secretion of these glycosylated mutant proteins is greatly
      increased in S. cerevisiae, compared with that of non-glycosylated type. Both the
      glycosylated mutants retained about 40% enzymatic activity when incubated at pH
      7.4 for 1 h at the physiological temperature of 37 degrees C whereas the non
      glycosylated proteins eventually lost all activity under these conditions. These
      results suggest that the glycosylated chains could mask the beta-strand of
      amyloidogenic lysozymes from the intermolecular cross-beta-sheet association,
      thus improving the solubility of amyloidogenic lysozymes.

PMID- 11226421
TI  - The ascorbate-driven reduction of extracellular ascorbate free radical by the
      erythrocyte is an electrogenic process.
AB  - Erythrocytes can reduce extracellular ascorbate free radicals by a plasma
      membrane redox system using intracellular ascorbate as an electron donor. In
      order to test whether the redox system has electrogenic properties, we studied
      the effect of ascorbate free radical reduction on the membrane potential of the
      cells using the fluorescent dye 3,3'-dipropylthiadicarbocyanine iodide. It was
      found that the erythrocyte membrane depolarized when ascorbate free radicals were
      reduced. Also, the activity of the redox system proved to be susceptible to
      changes in the membrane potential. Hyperpolarized cells could reduce ascorbate
      free radical at a higher rate than depolarized cells. These results show that the
      ascorbate-driven reduction of extracellular ascorbate free radicals is an
      electrogenic process, indicating that vectorial electron transport is involved in
      the reduction of extracellular ascorbate free radical.

PMID- 11226422
TI  - Circadian and photic regulation of MAP kinase by Ras- and protein phosphatase
      dependent pathways in the chick pineal gland.
AB  - Chick pineal mitogen-activated protein kinase (MAPK) exhibits circadian
      activation and light-dependent deactivation at nighttime. Here we report that, in
      the chick pineal gland, levels of active forms of MAPK, MEK, Raf-1 and Ras
      exhibited synchronous circadian rhythms with peaks during the subjective night,
      suggesting a sequential activation of components in the classical Ras-MAPK
      pathway in a circadian manner. In contrast, the light-dependent deactivation of
      MAPK was not accompanied by any change of MEK activity, but it was attributed to
      the light-dependent activation of protein phosphatase dephosphorylating MAPK.
      These results indicate that the photic and clock signals regulate MAPK activity
      via independent pathways, and suggest a pivotal role of MAPK in photic
      entrainment and maintenance of the circadian oscillation.

PMID- 11226423
TI  - Zinc and copper bind to unique sites of histatin 5.
AB  - Metal binding has been suggested to be relevant in the antifungal and
      antibacterial mechanism of histatin 5, a human salivary protein. Proton nuclear
      magnetic resonance (NMR) spectra were obtained to investigate the specificity of
      metal binding to the seven histidyl, one aspartyl and one glutamyl amino acid
      side-chains of histatin 5 in aqueous solutions. Three C(epsilon1)-H histidyl and
      the C(gamma)-H glutamyl resonances of histatin 5 were selectively altered in
      spectra of solutions containing three equivalents of zinc. Copper binding to
      histatin 5 resulted in a reduced intensity of C(beta)-H aspartyl resonances,
      while no evidence for calcium binding was found. These results indicate that zinc
      binding to histatin 5 involves His-15 present within the -H-E-X-X-H- zinc binding
      motif, and copper binding occurs within the N-terminal D-S-H-, ATCUN motif.

PMID- 11226424
TI  - An estimation of the size of the water cluster present at the cleavage site of
      the water splitting enzyme.
AB  - In time-dependent measurements of oxygen evolution in tobacco thylakoid membranes
      we varied the fraction of H(2)(18)O and the temperature and measured water
      splitting as (18)O(2), (16)O(18)O, and (16)O(2) by mass spectrometry. We show
      that the approach to the equilibrium of the system after H(2)(18)O addition can
      be very well understood in terms of the diffusion of water molecules. The
      equilibrium states of (16)O(2), (16)O(18)O, and (18)O(2) evolution differ from
      the theoretical binomial distributions, which are expected under the prerequisite
      of ideal mixing of the water molecules and that of the chemical equivalence of
      H(2)(18)O and H(2)(16)O for an infinite cluster. The presence of this deviation
      means that there is a typical size of water clusters having access to cleavage by
      the water splitting enzyme. We estimated that this cluster contains about 12+/-2
      water molecules.

PMID- 11226425
TI  - HIF-1-dependent transcriptional activity is required for oxygen-mediated HIF
      1alpha degradation.
AB  - Hypoxia-inducible factor-1alpha (HIF-1alpha) plays a central role in oxygen
      homeostasis. In normoxia, HIF-1alpha is a short lived protein, whereas hypoxia
      rapidly increases HIF-1alpha protein levels by relaxing its ubiquitin-proteasome
      dependent degradation. In this study, we show that the p42/p44 MAP kinase
      cascade, known to phosphorylate HIF-1alpha, does not modulate the
      degradation/stabilization profile of HIF-1alpha. However, we present evidence
      that the rate of HIF-1alpha degradation depends on the duration of hypoxic
      stress. We demonstrate that degradation of HIF-1alpha is suppressed by: (i)
      inhibiting general transcription with actinomycin D or (ii) specifically blocking
      HIF-1-dependent transcriptional activity. In keeping with these findings, we
      postulate that HIF-1alpha is targetted to the proteasome via a HIF-1alpha
      proteasome targetting factor (HPTF) which expression is directly under the
      control of HIF-1-mediated transcriptional activity. Although HPTF is not yet
      molecularly identified, it is clearly distinct from the von Hippel-Lindau protein
      (pVHL).

PMID- 11226426
TI  - Testosterone inhibits osteoclast formation stimulated by parathyroid hormone
      through androgen receptor.
AB  - Androgens play an important role in the regulation of bone metabolism in animals
      and humans. The present study was performed to investigate whether androgens
      would affect osteoclast formation stimulated by parathyroid hormone (PTH) in
      mouse bone cell cultures and its mechanism. Testosterone as well as alpha
      dihydrotestosterone (DHT) concentration-dependently inhibited osteoclast
      formation induced by PTH-(1-34). 10(-8) M ICI 182780, an estrogen receptor
      inhibitor, did not affect PTH-induced osteoclast formation antagonized by 10(-8)
      M testosterone, although it completely antagonized the effects of 10(-8) M 17beta
      estradiol. Moreover, 3 microM 4-androsten-4-ol-3,17-dione, an aromatase
      inhibitor, did not affect PTH-induced osteoclast formation antagonized by
      testosterone. Hydroxyflutamide, an androgen receptor antagonist, concentration
      dependently antagonized the inhibitory effects of testosterone as well as DHT on
      PTH-stimulated osteoclast formation. In conclusion, the present study first
      demonstrated that testosterone inhibited osteoclast formation stimulated by PTH
      through the androgen receptor, but not through the production of intrinsic
      estrogen in mouse bone cell cultures.

PMID- 11226427
TI  - Guide DNA technique reveals that the protein component of bacterial ribonuclease
      P is a modifier for substrate recognition.
AB  - We developed a guide DNA technique with which the cleavage efficiency of pre-tRNA
      substrate raised in the RNase P reaction. The 20-mer guide DNAs hybridizing to
      the upstream region of the cleaving site enhanced the cleavage reactions of RNA
      substrates by Escherichia coli RNase P. This guide DNA technique was also
      applicable to cleavage site selection by choosing the DNA-hybridizing site.
      Results showed that RNase P accepts DNA/RNA double-stranded 5'-leader region with
      high catalytic efficiency as well as single-stranded RNA region in pre-tRNAs as
      substrates, which suggests that the protein component of bacterial RNase P
      prefers bulky nucleotides. The protein component did not affect the normal 5'
      processing reaction of pre-tRNAs, but enhanced the mis-cleaving (hyperprocessing)
      reactions of tRNA in non-cloverleaf folding. Our results suggested that the
      protein component of RNase P is a modifier for substrate recognition.

PMID- 11226428
TI  - Extracellular Ba2+ and voltage interact to gate Ca2+ channels at the plasma
      membrane of stomatal guard cells.
AB  - Ca2+ channels at the plasma membrane of stomatal guard cells contribute to
      increases in cytosolic free [Ca2+] ([Ca2+](i)) that regulate K+ and Cl- channels
      for stomatal closure in higher-plant leaves. Under voltage clamp, the initial
      rate of increase in [Ca2+](i) in guard cells is sensitive to the extracellular
      divalent concentration, suggesting a close interaction between the permeant ion
      and channel gating. To test this idea, we recorded single-channel currents across
      the Vicia guard cell plasma membrane using Ba2+ as a charge carrying ion. Unlike
      other Ca2+ channels characterised to date, these channels activate at
      hyperpolarising voltages. We found that the open probability (P(o)) increased
      strongly with external Ba2+ concentration, consistent with a 4-fold cooperative
      action of Ba2+ in which its binding promoted channel opening in the steady state.
      Dwell time analyses indicated the presence of a single open state and at least
      three closed states of the channel, and showed that both hyperpolarising voltage
      and external Ba2+ concentration prolonged channel residence in the open state.
      Remarkably, increasing Ba2+ concentration also enhanced the sensitivity of the
      open channel to membrane voltage. We propose that Ba2+ binds at external sites
      distinct from the permeation pathway and that divalent binding directly
      influences the voltage gate.

PMID- 11226429
TI  - Inhibition of caspase-1 induces cell death in pancreatic carcinoma cells and
      potentially modulates expression levels of bcl-2 family proteins.
AB  - Caspase-1 (interleukin-1beta-converting enzyme) is reported to play an important
      role in the regulation of apoptosis. We investigated the inhibition of caspase-1
      by the cell permeable caspase-1 inhibitor Ac-AAVALLPAVLLALLAP-YVAD.CHO in
      pancreatic carcinoma cells. Inhibition of caspase-1 induced a non
      apoptotic/"necrotic-like" cell death in AsPC-1, BxPC-3, MiaPaCa-2 and Panc-1
      cells. Expression levels of bcl-2 and bax were up-regulated in caspase-1
      inhibitor-treated cells while that of bcl-x(L) remained unaltered. Our
      observations support our previous findings that caspase-1 is potentially involved
      in anti-apoptotic processes in pancreatic carcinoma.

PMID- 11226430
TI  - Involvement of uncoupled antenna chlorophylls in photoinhibition in thylakoids.
AB  - Evidence is presented, by means of both fluorescence and action spectroscopy,
      that a small, spectroscopically heterogeneous population of both Chl a and Chl b
      molecules is present in isolated spinach thylakoids and is active in
      photoinhibition. The broadness of the action spectrum suggests that degraded or
      incompletely assembled pigment-protein complexes may be involved.

PMID- 11226431
TI  - Aging but not dietary restriction alters the activation-induced apoptosis in rat
      T cells.
AB  - The aim of this study was to determine if aging or dietary restriction (DR)
      alters activation-induced cell death, which is known to regulate cell
      proliferation and eliminate the high number of activated cells during an immune
      response. Splenic T cells were isolated from young (4-6 months) and old (25-26
      months) Fischer 344 rats that had free access to food, ad libitum (AL), and from
      dietary-restricted (DR) old (25-26 months) rats that beginning at 6 weeks of age
      were fed 60% (40% food-restricted) of the diet consume by the AL rats. T cells
      were incubated with anti-CD3 antibody, or staphylococcal enterotoxin B (primary
      stimulus) for 72-96 h, followed by restimulation with anti-CD3 (secondary
      stimulus) for 72 h. Activation-induced apoptosis was assessed by DNA
      fragmentation and the expression of Fas/CD95 receptor and Fas ligand (Fas-L) was
      measured by flow cytometry. We found that the amount of DNA fragmentation was
      significantly (P<0.05) higher in the stimulated and restimulated T cells from AL
      old rats and DR old rats compared to young rats. The increase in DNA
      fragmentation with age was paralleled by an increase in the proportion of the
      cells expressing Fas and Fas-L. However, DR had no significant effect on the age
      related increase in DNA fragmentation or the expression of Fas or Fas-L. We also
      measured the levels of Bcl-2 and Bax protein and found that the level of Bcl-2
      decreased and Bax increased with age and that DR had no effect on the age-related
      changes in the level of Bcl-2 or Bax protein. These results demonstrate that
      aging but not DR alters activation-induced apoptosis in rat T cells.

PMID- 11226432
TI  - Chromaffin granule membranes contain at least three heme centers: direct evidence
      from EPR and absorption spectroscopy.
AB  - Low-temperature electron paramagnetic resonance (EPR) spectroscopy, circular
      dichroism and two-component redox titration have previously provided evidence for
      two different ascorbate-reducible heme centers in cytochrome b(561) present in
      chromaffin granule membranes. These species have now been observed by room and
      liquid nitrogen temperature absorption spectroscopy. The visualization of these
      heme centers becomes possible as a consequence of utilizing chromaffin granule
      membranes prepared by a mild procedure. Additionally, a new redox center, not
      reducible by ascorbate, was discovered by both EPR and absorption spectroscopy.
      It constitutes about 15% of the heme absorbance of chromaffin membranes at 561 nm
      and has EPR characteristics of a well-organized highly axial low-spin heme center
      (thus making it unlikely that it is a denatured species). This species is either
      an alternative form of one of the hemes of cytochrome b(561) that has a very low
      redox potential or a b-type cytochrome distinct from b(561).

PMID- 11226433
TI  - Different susceptibility to oxidation of proline and arginine residues of
      apolipoprotein B-100 among subspecies of low density lipoproteins.
AB  - gamma-Glutamyl semialdehyde is a primary oxidation product of apolipoprotein
      (apo) B-100 proline (Pro) and arginine (Arg) side chain residues. By reduction
      gamma-glutamyl semialdehyde forms 5-hydroxy-2-aminovaleric acid (HAVA). Here we
      describe the application of sensitive and specific HAVA measurement to
      characterize the formation of gamma-glutamyl semialdehyde in several domains of
      apoB-100 in LDL(1) (S(f) 7-12) and LDL(2) (S(f) 0-7) subfractions subjected to
      oxidative damage in the presence of iron in vitro. Results suggest that
      susceptibility of apoB-100 Pro and Arg residues toward oxygen radicals
      drastically changes along the lipoprotein metabolic cascade.

PMID- 11226434
TI  - Role of Thr(11) in the binding of omega-conotoxin MVIIC to N-type Ca2+ channels.
AB  - As replacement of Thr(11) of omega-conotoxin MVIIC with Ala significantly reduced
      the affinity for both N- and P/Q-type calcium channels, we examined the effect of
      substitution at this position with other residues. Binding assays using rat
      cerebellar P2 membranes showed that the affinity is in the order of Leu>Val,
      aminobutyric acid, Thr>Asn&z.Gt;Ser, Ala, Asp, Phe, Tyr for N-type channels and
      Thr>Leu, Val, aminobutyric acid, Asn, Ser>Ala&z.Gt;Asp, Phe, Tyr for P/Q-type
      channels, suggesting that aliphatic amino acids with longer side chains are
      favorable for block of N-type channels. The effects of substitution were examined
      electrophysiologically in BHK cells expressing N-type Ca2+ channels. Inhibition
      of Ba2+ current by the analogs did not completely correlate with binding
      affinity, although binding to BHK cells was comparable to rat cerebellar
      membranes.

PMID- 11226435
TI  - An essential role for calmodulin in regulating human T cell aggregation.
AB  - After activation of T cells with either CD3 antibodies or phorbol esters, we have
      found that T cell-cell aggregation, integrin-dependent actin reorganisation and
      cell spreading are strongly suppressed by any of three structurally different
      calmodulin antagonists, without any effect on the amount of CD11/CD18 integrin
      binding to the actin cytoskeleton. However, only T cell receptor-induced, and not
      phorbol ester-induced, aggregation and cell spreading are prevented by inhibitors
      of phosphatidylinositide (PI) 3-kinase. These results suggest that PI 3-kinase
      lies upstream of calmodulin in the signalling pathway leading to T cell
      aggregation, cell spreading and actin reorganisation and that cell spreading and
      actin reorganisation are essential for T cell adhesion.

PMID- 11226436
TI  - Catalytic activities of membrane-type 6 matrix metalloproteinase (MMP25).
AB  - This study describes the biochemical characterisation of the catalytic domain of
      membrane-type 6 matrix metalloproteinase (MT6-MMP, MMP25, leukolysin). Its
      activity towards synthetic peptide substrates, components of the extracellular
      matrix and inhibitors of MMPs was studied and compared with MT1-MMP, MT4-MMP and
      stromelysin-1. We have found that MT6-MMP is closer in function to stromelysin-1
      than MT1 and MT4-MMP in terms of substrate and inhibitor specificity, being able
      to cleave type-IV collagen, gelatin, fibronectin and fibrin. However, it differs
      from stromelysin-1 and MT1-MMP in its inability to cleave laminin-I, and unlike
      stromelysin-1 cannot activate progelatinase B. Our findings suggest that MT6-MMP
      could play a role in cellular migration and invasion of the extracellular matrix
      and basement membranes and its activity may be tightly regulated by all members
      of the TIMP family.

PMID- 11226437
TI  - Probing the binding sites of exchanged chlorophyll a in LH2 by Raman and site
      selection fluorescence spectroscopies.
AB  - In this work we have selectively released the 800 nm absorbing
      bacteriochlorophyll a molecules of the LH2 protein from the photosynthetic
      bacterium Rhodopseudomonas acidophila, strain 10050, and replaced them with
      chlorophyll a (Chla). A combination of low-temperature electronic absorption,
      resonance Raman and site-selection fluorescence spectroscopies revealed that the
      Chla pigments are indeed bound in the B800 binding site; this is the first work
      that formally proves that such non-native chlorins can be inserted correctly into
      LH2.

PMID- 11226438
TI  - GPI-anchored proteins and glycoconjugates segregate into lipid rafts in
      Kinetoplastida.
AB  - The plasma membranes of the divergent eukaryotic parasites, Leishmania and
      Trypanosoma, are highly specialised, with a thick coat of glycoconjugates and
      glycoproteins playing a central role in virulence. Unusually, the majority of
      these surface macro-molecules are attached to the plasma membrane via a
      glycosylphosphatidylinositol (GPI) anchor. In mammalian cells and yeast, many GPI
      anchored molecules associate with sphingolipid and cholesterol-rich detergent
      resistant membranes, known as lipid rafts. Here we show that GPI-anchored
      parasite macro-molecules (but not the dual acylated Leishmania surface protein
      (hydrophilic acylated surface protein) or a subset of the GPI-anchored
      glycoinositol phospholipid glycolipids) are enriched in a sphingolipid/sterol
      rich fraction resistant to cold detergent extraction. This observation is
      consistent with the presence of functional lipid rafts in these ancient, highly
      polarised organisms.

PMID- 11226439
TI  - Fenofibrate prevents and reduces body weight gain and adiposity in diet-induced
      obese rats.
AB  - Fibrates are hypolipidemic drugs that activate the peroxisome proliferator
      activated receptors. Since fibrates may also increase energy expenditure, we
      investigated whether fenofibrate (FF) had this effect in diet-induced obese rats.
      A 2-month administration of a high-fat palatable diet to adult rats increased
      body weight by 25% and white adipose mass by 163% compared with a standard diet.
      These effects were prevented by FF, both when administered for the 2 months of
      high-fat feeding and when given for only the second month. Consequently, FF
      treated rats had a final body weight and white adipose tissue mass similar to
      untreated animals on the standard diet. FF also increased resting metabolic rate,
      hepatic peroxisomal and mitochondrial palmitoyl-dependent oxygen uptake and mRNA
      levels of acyl-CoA oxidase and lipoprotein lipase. Finally, FF lowered mRNA
      levels of uncoupling protein-2 and did not affect mitochondrial respiration in
      skeletal muscle. Therefore, FF seems to act as a weight-stabilizer mainly through
      its effect on liver metabolism.

PMID- 11226440
TI  - Antibacterial activity of a pepsin-derived bovine hemoglobin fragment.
AB  - Peptic digestion of bovine hemoglobin yields a fragment with antibacterial
      activity. This peptide was purified to homogeneity by a two-step procedure
      including anion exchange chromatography and preparative reversed-phase HPLC. Mass
      determination and fragmentation indicated that this peptide corresponded to the 1
      23 fragment of the alpha chain of hemoglobin. The minimum inhibitory
      concentration and mode of action of this peptide towards Micrococcus luteus
      strain A270 were determined. Hemolytic assay, interaction with liposomes, and
      study of its structure in solution were also performed.

PMID- 11226441
TI  - Oral misoprostol vs. placebo in the management of prelabor rupture of membranes
      at term.
AB  - OBJECTIVE: To evaluate the efficacy of oral misoprostol for the induction of
      labor (IOL) in women with prelabor rupture of membranes at term (PROM) and to
      monitor maternal or fetal complications. METHOD: This randomized, placebo
      controlled trial was performed in a secondary referral hospital. The data of 47
      patients in the misoprostol--and 49 patients in the placebo group was available
      for analysis. The former received 100 microg misoprostol orally, repeated once
      after 6 h if not in active labor, the latter received two doses of vitamin C also
      after a 6-h interval. The Mann-Whitney U-test was used for analysis. RESULTS: The
      median treatment to delivery interval in the misoprostol group was 7.5 h and 25 h
      in the placebo group (P<0.001). No significant differences were found in the
      incidence of abnormalities on the cardiotocograph, mode of delivery, neonatal
      outcome, use of antibiotics for the mothers and patient acceptability.
      CONCLUSION: Oral misoprostol in the suggested dose is an effective and cheap
      alternative for IOL in patients with PROM. No adverse effects could be
      demonstrated.

PMID- 11226442
TI  - A longitudinal study of amniotic fluid index in normal pregnancy in Nigerian
      women.
AB  - OBJECTIVE: To establish normal reference values of amniotic fluid index by week
      of gestation for normal pregnancies in our population. METHOD: A longitudinal
      prospective assessment of amniotic fluid index in healthy pregnant women carrying
      singleton pregnancies. The subjects were recruited at 20 or 22 weeks of gestation
      and concluded at 40 or 42 weeks of gestation. The numeral data were analyzed on
      an IBM Personal System 2 computer with statistical and graphical packages.
      RESULT: from a mean of 17.18 cm at 20 weeks gestation, the amniotic fluid index
      rose progressively to a peak of 20.39 cm at 26 weeks gestation. It then gradually
      declined to a mean of 8.37 cm at 42 weeks gestation. CONCLUSION: Gestational age
      specific values of amniotic fluid index should be used and the 5th and 95th
      percentiles taken as lower and upper limits of normal, respectively.

PMID- 11226443
TI  - Active management of labor: is it suitable for a developing country?
AB  - OBJECTIVE: To evaluate the effectiveness of active management of labor in the
      setting of a developing country. METHODS: This historical cohort study compared
      the labor characteristics and outcome of all anti-HIV positive nulliparous
      pregnant women (n=96), who delivered between January 1991 and March 1999, treated
      with traditional labor management to all anti-HIV negative nulliparous pregnant
      women (n=1856), who delivered in 1998, treated with active management of labor in
      the tertiary center of a developing country. The year 1998 was chosen by using
      the total cesarean section rate of nulliparous patients from 1991 to 1998 to find
      the mean, then selected the year with cesarean section rate nearest to the mean
      as a control. Data were analyzed by the chi-square and t-tests. RESULTS: The
      length of labor was significantly shortened in the active management group (6.3+/
      3.3 h vs. 8.9+/-6 h, P<0.001). A significantly greater proportion of the
      traditional management group had prolonged labor (29.3% vs. 4.9%, P<0.001).
      However, the cesarean section rate was not different between the two groups
      (active vs. traditional=17% vs. 14.6%, P=0.7) with dystocia as a major indication
      in both groups. Maternal and fetal complications were not different. CONCLUSION:
      The active management of labor shortened the duration of labor and reduced
      prolonged labor; however, it did not decrease the cesarean section rate.

PMID- 11226444
TI  - Constant estrogen, intermittent progestogen vs. continuous combined hormone
      replacement therapy: tolerability and effect on vasomotor symptoms.
AB  - OBJECTIVE: To compare the efficacy and tolerability of a novel oral constant
      estrogen plus intermittent progestogen hormone replacement therapy (HRT) regimen
      to a continuous combined HRT regimen in postmenopausal women. METHODS: Subjects
      were randomly assigned to receive treatment with either constant 17beta-estradiol
      (E2), 1 mg, plus intermittent norgestimate (NGM) 90 microg (3 days off, 3 days
      on) (n=221) or E2 2 mg/norethisterone acetate (NETA) 1 mg (n=217) for 1 year.
      Treatments were evaluated based on the incidence of hot flushes and uterine
      bleeding. RESULTS: Both regimens had similar bleeding profiles and provided
      comparable vasomotor symptom relief. However, breast discomfort and edema were
      experienced by twice as many subjects who received E2/NETA. CONCLUSIONS: The
      constant E2/intermittent NGM regimen was well tolerated and possesses similar
      efficacy compared with a continuous combined E2/NETA regimen and may be
      considered whenever HRT without withdrawal bleeding is deemed appropriate.

PMID- 11226445
TI  - Termination of early pregnancy in the scarred uterus with mifepristone and
      misoprostol.
AB  - OBJECTIVE: To analyze the safety and possibility of terminating early pregnancy
      up to 49 days gestation after cesarean section with mifepristone and misoprostol.
      METHODS: One-hundred and ninety-two early pregnant women were recruited, of
      which, 35 cases with uterine cicatrix and 157 cases were no-uterine cicatrix as
      control group. All of them took 25 mg of mifepristone, b.i.d. for 3 days and 600
      microg of misoprostol on the 4th day. RESULTS: Of the 35 cases with uterine
      cicatrix, 33 achieved complete abortion after medical abortion. The complete
      abortion rate was 94.29% (95% CI 81-99%) in the cicatrix group and 89.81% (95% CI
      75-91%) in the control group. There were no obvious complications detected in the
      cicatrix group. CONCLUSION: For the termination of early pregnancy in scarred
      uterus, administration of mifepristone and misoprostol is safe and effective, and
      a further large series study needs be done to confirm its acceptability as a
      routine medication in such situations.

PMID- 11226446
TI  - Uterine artery embolization in a 10-week cervical pregnancy with coexisting
      fibroids.
AB  - A 36-year-old woman, gravid 3, para 1, abortus 1, was admitted to our department
      at 10 weeks and 4 days of gestation with the diagnosis of cervical pregnancy and
      multiple uterine fibroids. After admission she underwent angiographic
      embolization of bilateral uterine arteries followed by intraamniotic 70-mg
      methotrexate injection. Despite being given a second dose of methotrexate
      injection 1 week later, the gestational sac did not resolve spontaneously, thus
      vacuum evacuation and curettage of the cervical canal was required on the 15th
      day of embolization. The patient was discharged in good condition. She had no
      complaints by post-operative at month 11, except amenorrhea. Her uterine fibroids
      markedly decreased in size after the procedure. As a result, embolization of
      uterine arteries provided surgical evacuation of cervical pregnancy with minimal
      hemorrhage, and the patient's potential fertility was preserved, but a long-term
      amenorrhea was observed.

PMID- 11226447
TI  - A new device for safer collection of postpartum cord blood.

PMID- 11226448
TI  - Can Down syndrome cause persistent non-reactive non-stress test?

PMID- 11226449
TI  - Adaptive physiological processes in the host during gastrointestinal parasitism.
AB  - Parasite infection of the gastrointestinal tract with helminths or protozoa
      induces detrimental effects on host tissues and host physiology, which have been
      extensively studied and reviewed. However, parasitism of the digestive system is
      also associated with adaptive, compensatory phenomena based on changes in host
      physiology or structures and which tend to counterbalance the negative
      consequences. The objective of this review is to describe these adaptive
      processes and their possible underlying mechanisms. Different processes which
      tend to attenuate the effect of either the loss of appetite, the intestinal
      malabsorption or the increased tissue losses have been assessed. These processes
      have been reported both for helminth and protozoan infections, where they present
      similar characteristics. The mechanisms involved in the adaptation to parasitism
      remain largely unidentified. The role of feedback mechanisms based on host
      regulation, possibly through gastrointestinal hormones, has been raised. On the
      other hand, some data support the proposal that parasites themselves may initiate
      some of the adaptive processes and consequently favour their own survival. These
      adaptive phenomena appear to be an essential component in the dynamic balance
      between host and parasites. Also, parasite infections represent unique models to
      study the adaptation of the gastrointestinal tract to aggressors.

PMID- 11226450
TI  - A protein with lectin activity in penetration glands of Diplostomum
      pseudospathaceum cercariae.
AB  - Homogenates of Diplostomum pseudospathaceum cercariae agglutinated mouse
      erythrocytes. The haemagglutination could be inhibited by certain glycoconjugates
      containing beta-1,3- and beta-1,4-glycan chains and also by some simple
      saccharides. The most potent inhibitors were heparin and some other
      glycosaminoglycans, bacterial lipopolysaccharides, laminarin (a beta-1,3-glucan)
      and lactulose. After electrophoresis of cercarial proteins, a dominant double
      band appeared in the 22-24 kDa region of gels. On blots, this protein bound
      labelled laminarin and it was also one of the few proteins recognised by mouse
      antibodies raised against cercarial haemagglutinins. In addition, mouse
      polyclonal antibodies against the beta-1,3-glucan-binding protein bound
      exclusively to the 22-24 kDa region on Western blots. Histochemistry revealed
      strong binding of labelled laminarin to cercarial penetration glands; this
      reaction was fully blocked by unlabelled laminarin. Other labelled
      glycoconjugates such as heparin, hyaluronic acid and a bacterial
      lipopolysaccharide also bound to the glands. Immunohistochemistry confirmed the
      localisation of the beta-1,3-glucan-binding protein in penetration glands.
      Reaction of the cercarial protein with immunoglobulins from non-immunised mice
      was observed on both nitrocellulose membranes and histological sections; this
      could be blocked by laminarin in incubation buffers. We consider the cercarial
      haemagglutinin to be a lectin which is identical with the 22-24 kDa beta-1,3
      glucan-binding protein. According to the binding specificity and localisation we
      speculate on a role of this lectin in cercarial penetration into the host,
      probably as a tissue recognition or antibody rendering factor.

PMID- 11226451
TI  - Molecular comparison of the dense granule proteins GRA6 and GRA7 of Neospora
      hughesi and Neospora caninum.
AB  - Neospora hughesi is a recently described apicomplexan parasite that has been
      associated with several cases of equine protozoal myeloencephalitis. The biology
      of this new parasite is just beginning to be defined. Towards this understanding,
      we report important differences between the nucleotide and deduced amino acid
      sequences of the dense granule proteins GRA6 and GRA7 of N. hughesi and Neospora
      caninum. This information can be used to differentiate the two species and
      contribute to further understanding of the prevalence and biology of N. hughesi.
      The newly defined proteins of N. hughesi are referred to as NhGRA6 and NhGRA7 in
      keeping with the protocol for naming homologous proteins of the Apicomplexa.
      Genes of the two dense granule proteins of N. hughesi (isolate Nh-A1) and four
      different isolates of N. caninum were isolated via PCR and their DNA sequences
      were determined. Computer analysis indicated that the two gene sequences were
      identical among all four N. caninum isolates. However, the gene for NhGRA6 was
      found to be 96 nucleotides longer at the 3' end than that of NcGRA6, resulting in
      a protein product that is 32 amino acids larger than NcGRA6. Two tandem repeat
      sequences were identified at the 3' end of the NhGRA6 gene. These repeat
      sequences contributed to the lengthening of the carboxy terminus of NhGRA6 in
      comparison with that of NcGRA6. The larger size of NhGRA6 was further confirmed
      by Western blot analysis in which NcGRA6 monospecific antibodies recognised a
      protein of approximately 42 kDa in N. hughesi whole tachyzoite preparation but a
      protein of 37 kDa in N. caninum whole tachyzoite preparation. Analysis of GRA7
      gene sequences indicated a 6 and 14.8% difference at nucleotide and amino acid
      sequence level, respectively, between NcGRA7 and NhGRA7. Despite the same number
      of residues in the deduced amino acid sequences of all the GRA7 proteins, Western
      blot analysis indicated a difference in the migration pattern of NhGRA7 in
      comparison with NcGRA7. Results of our study indicate that diagnostic tests based
      on differences in dense granule sequences and antigenicity may have potential to
      differentiate between N. hughesi and N. caninum. Such diagnostic tests would be
      valuable tools to aid in our understanding of the epidemiology of these
      parasites. Additionally, dense granule proteins are immunogenic and they may have
      potential as use in recombinant vaccines against neosporosis.

PMID- 11226452
TI  - Isolation and characterisation of genomic and cDNA clones coding for a serine-,
      alanine-, and proline-rich protein of Trypanosoma cruzi.
AB  - We report here the isolation and characterisation of genomic and cDNA clones
      encoding a Serine-, Alanine-, and Proline-rich protein (SAP) of Trypanosoma cruzi
      metacyclic trypomastigotes. The deduced peptides translated from these clones
      were characterised by a high content of residues of alanine, proline, serine,
      glycine, valine, and threonine distributed in several repeats: P(2-4), S(2-3),
      A(2-3), AS, SA, PA, AP, SP, PS, and TP. The repeats are partially homologous to
      the serine-, alanine-, and proline-containing motifs of Leishmania major and
      Leishmania mexicana proteophosphoglycans. Genes coding for SAP are part of a
      polymorphic family whose members are linked to members of gp85/sialidase and
      mucin-like gene families. This is consistent with the hypothesis that this
      genetic organisation could be a means by which T. cruzi co-ordinates the
      expression of major surface proteins.

PMID- 11226453
TI  - Down-regulation of human B lymphocyte activities by a Trypanosoma cruzi membrane
      glycoprotein.
AB  - The effects of purified AGC10, a Trypanosoma cruzi membrane glycoprotein, on
      normal human B lymphocytes were studied in this work. In the presence of AGC10,
      [3H]-thymidine uptake by human peripheral blood mononuclear cells stimulated with
      the B cell-specific mitogen SACI (killed Staphylococcus aureus Cowan I) was
      markedly decreased. This alteration was accompanied by others such as decreased
      expression of the CD122 and CD132 chains of the IL-2R complex. These inhibitory
      effects appeared to be somewhat selective, as expression of CD25, another IL-2R
      chain, was not affected by AGC10 and no significant modification occurred in the
      expression of the B-cell-specific marker CD19 or CD21. In contrast, AGC10 did
      reduce the levels of expression of CD86 and CD80, molecules known to play
      critical roles in B cell interactions with T lymphocytes. Fairly large
      subpopulations of, but not all, B lymphocytes had their expression of CD122(+),
      CD132(+), CD86(+) and CD80(+) reduced to undetectable levels in the presence of
      AGC10. However, the SACI-activated B cells that remained capable of expressing
      these molecules in the presence of AGC10 did so at normal levels. This was
      denoted by comparable mean fluorescence intensity values representing the
      expression of CD122, CD132, CD86 or CD80 molecules on the surface of SACI
      stimulated CD19(+) cells cultured without or with AGC10. These results indicated
      that AGC10, derived from an organism that causes immunosuppression in infected
      hosts, down-regulates B cell activities and suggested that the relevant mechanism
      could involve the molecular alterations described above.

PMID- 11226454
TI  - Immunoglobulin subclass responses of wild brown rats to Sarcocystis
      singaporensis.
AB  - Immunoglobulin subclass responses of wild brown rats (Rattus norvegicus) from
      southeastern Asia to the endemic cyst-forming coccidian Sarcocystis singaporensis
      were characterised. The antibody response of brown rats to wild-type parasites
      (high reproductive capacity) showed a Th1 profile during acute infection, namely
      elevated concentrations of parasite-specific IgG2b and IgG2c and absence of IgG1.
      Chronic infection (bradyzoite development) resulted in a mixed Th1/Th2 pattern
      whereby significant concentrations of IgG1 appeared. A primary infection with
      1000 sporocysts eight days before challenge induced protection, accompanied by
      significant concentrations of IgA and IgG2, particularly IgG2a. Western blot
      analysis of rat sera, using sporozoite and bradyzoite-extracts as antigen,
      revealed that IgG1, IgG2a, and IgG2b predominantly recognised molecules between
      70-80 kDa in one or the other stage. Some of the antibodies were possibly
      directed against a 79 kDa heat shock protein of sporozoites. An apparent
      unresponsiveness to molecules in the low molecular weight range, particularly of
      bradyzoite antigens, was observed. This was abrogated by infection of rats with
      an avirulent strain of S. singaporensis (low reproductive capacity) indicating
      that a parasite that was less adapted to its host provoked a stronger immune
      response. These results suggest the existence of an immune evasion strategy used
      by Sarcocystis and show that wild rodents may be suitable as immunological
      research objects, reflecting the natural situation.

PMID- 11226455
TI  - Effects on the neutral lipid contents of the liver, ileum and serum during
      experimental schistosomiasis.
AB  - During infection of vertebrate hosts with Schistosoma mansoni,worm eggs trapped
      in host tissues induce granulomatous lesions that interfere with normal organ
      functions. Even though both the liver and the intestine are particularly
      susceptible to egg-induced tissue damage, little information is available on the
      pathobiochemical changes induced in these organs during infection. Using a mouse
      model, we investigated whether the lipid profiles of the liver and ileum were
      altered significantly as a result of infection. We found that triacylglycerol and
      cholesteryl ester levels decreased significantly as infection progressed.

PMID- 11226456
TI  - Molecular and phylogenetic characterisation of Cryptosporidium from birds.
AB  - Avian isolates of Cryptosporidium species from different geographic locations
      were sequenced at two loci, the 18S rRNA gene and the heat shock gene (HSP-70).
      Phylogenetic analysis of the sequence data provided support for the existence of
      a new avian species of Cryptosporidium infecting finches and a second species
      infecting a black duck. The identity of Cryptosporidium baileyi and
      Cryptosporidium meleagridis as valid species was confirmed. Also, C. baileyi was
      identified in a number of isolates from the brown quail extending the host range
      of this species.

PMID- 11226457
TI  - Trichinella pseudospiralis populations of the Palearctic region and their
      relationship with populations of the Nearctic and Australian regions.
AB  - Since few non-encapsulated isolates of Trichinella have been studied to date,
      their level of differentiation from encapsulated species and the taxonomic value
      of the observed polymorphisms remain to be determined. To this end, biological,
      biochemical and molecular data from 11 isolates of Trichinella pseudospiralis and
      one isolate of Trichinella papuae were examined using the broad group of
      encapsulated species and genotypes for comparison. Single-worm cross-breeding
      experiments and reproductivity capacity indices revealed F1 progeny only among T.
      pseudospiralis isolates from different zoogeographical regions, whereas no F1
      were produced when T. pseudospiralis was crossed with T. papuae. Furthermore,
      unlike T. pseudospiralis, T. papuae failed to infect chickens. Comparative
      analysis of 12 allozymes revealed a single difference between Nearctic and
      Australian isolates of T. pseudospiralis, but substantial differences when
      compared with T. papuae (i.e. two unique and six diagnostic markers). Molecular
      studies involving mitochondrial-derived genes encoding cytochrome oxidase I and
      the large subunit ribosomal DNA indicated a high level of sequence similarity
      among T. pseudospiralis isolates; however, a concomitantly high level of
      variation was observed in expansion segment five of the genomic large subunit
      ribosomal DNAs among T. pseudospiralis isolates and between this species and T.
      papuae. Collectively, these results demonstrate high uniformity among isolates of
      T. pseudospiralis from Eurasia and polymorphism among isolates of T.
      pseudospiralis belonging to different zoogeographical regions; the results
      corroborate the classification of T. papuae as a differentiated species.

PMID- 11226458
TI  - Immunisation of cattle with recombinant acetylcholinesterase from Dictyocaulus
      viviparus and with adult worm ES products.
AB  - Dictyocaulus viviparus causes a serious lung disease of cattle. For over 30
      years, a radiation-attenuated larval vaccine has been used with success; however,
      this vaccine has several disadvantages. A more stable vaccine against D.
      viviparus, capable of stimulating prolonged protective immunity, would be
      beneficial. Recent research has been directed at adult worm ES components that
      may be involved in parasite survival in the host. One component is the secreted
      enzyme, acetylcholinesterase (AChE), a target for circulating antibody in
      infected calves. Here, we describe a study where protection was investigated in
      calves immunised with either native adult ES products or a recombinant parasite
      AChE. These antigens were administered twice with Freund's incomplete adjuvant.
      Subsequently, all calves were challenged with 700 L3 and their worm burdens and
      immune responses compared with those in calves that received an anthelmintic
      abbreviated infection and challenge control calves. Significant levels of
      protection were not obtained in the immunised groups but significant immunity was
      achieved in the calves that received the anthelmintic abbreviated infection.
      Antibody responses amongst the groups were different, with significantly higher
      IgG1 responses in the immune, infected group and in adult ES recipients.
      Significantly higher IgG2 responses were found in the latter group. Following
      challenge, the groups that received the abbreviated infection and the fusion
      protein produced specific antibody that bound the native enzyme. No differences
      were observed between groups in peripheral blood mononuclear cell responsiveness
      to either antigen. However, adult ES products appeared to have a mitogenic effect
      on these cells, whilst the fusion protein exhibited an inhibitory effect. These
      results suggest that in this form, AChE is not a potential vaccine candidate and
      that adult ES products, in contrast to previous experiments in guinea pigs, do
      not contain protective components.

PMID- 11226459
TI  - The chicken B cell line DT40: a novel tool for gene disruption experiments.
AB  - The use of the chicken DT40 B cell line is increasing in popularity due to the
      ease with which it can be manipulated genetically. It offers a targeted to random
      DNA integration ratio of more than 1:2, by far exceeding that of any mammalian
      cell line. The facility with which knockout cell lines can be generated, combined
      with a short generation time, makes the DT40 cell line attractive for phenotype
      analysis of single and multiple gene disruptions. Advantage has been taken of
      this to investigate such diverse fields as B cell antigen receptor (BCR)
      signaling, cell cycle regulation, gene conversion and apoptosis. In this review,
      we give a historical introduction and a practical guide to the use of the DT40
      cell line, along with an overview of the main topics being researched using the
      DT40 cell line as a model system. These topics include B cell-specific subjects
      such as B cell signaling and Ig rearrangement, and subjects common to all cell
      types such as apoptosis, histones, mRNA modification, chromosomal maintenance and
      DNA repair. Attention is in each case brought to peculiarities of the DT40 cell
      line that are of relevance for the subject. Novel applications of the cell line,
      e.g., as a vector for gene targeting of human chromosomes, are also discussed in
      this review.

PMID- 11226460
TI  - The use of post-source decay in matrix-assisted laser desorption/ionisation mass
      spectrometry to delineate T cell determinants.
AB  - The identification of naturally processed peptides presented by molecules of the
      major histocompatibility complex (MHC) has progressed significantly over the past
      decade. The elution of peptides from immunoaffinity purified complexes of MHC
      class I or class II molecules has provided highly specific biochemical
      information regarding the nature of endogenous peptides capable of binding to and
      being presented by particular MHC alleles. Whilst Edman chemistry is sufficient
      for the identification of abundant or homogeneous immunodominant peptides
      contained in samples of fractionated peptides, mass spectrometry has proved more
      powerful for sequencing less abundant species present in the typically
      heterogeneous fractions of eluted peptides. This review focuses on the
      characterisation of T cell determinants by matrix-assisted laser
      desorption/ionisation (MALDI)-time-of-flight (TOF) mass spectrometry (MS). We
      demonstrate, with specific examples, the utility of post-source decay in MALDI
      TOF MS for the characterisation of the amino acid sequences of both native and
      modified T cell determinants. The potential advantages and pitfalls of this
      technique relative to the more commonly used forms of tandem mass spectrometry in
      electrospray and ion spray modes of ionisation as well as hybrid quadrupole
      quadrupole-TOF instruments are discussed. We highlight the complementarity
      between these techniques and discuss the advantages in the combined use of both
      MALDI- and electrospray-based instrumentation in epitope identification
      strategies.

PMID- 11226461
TI  - A general affinity method to purify peroxidase-tagged antibodies.
AB  - Antibodies tagged with enzymes, e.g. horseradish peroxidase (HRPO) are used
      extensively in a broad range of immunoassay, immunohistochemical, and prodrug
      based immunotherapeutic applications. These antibodies may be polyclonal,
      monoclonal, bispecific or genetically engineered in origin. Often, purification
      of the antibody is the single greatest obstacle to obtaining immunoprobes with
      high specific activity [Milstein and Cuello, Nature 305 (1983) 537]. We have
      circumvented this problem by utilising benzhydroxamic acid-agarose to purify the
      antibodies tagged with HRPO as a preformed immune complex. Benzhydroxamic acid
      has been shown to have affinity for the active site of HRPO [de Ropp et al.,
      Biochemistry 38 (1999) 1077]. A preliminary ammonium sulfate precipitation of 250
      ml of bispecific antibody supernatant was performed and the pellet resuspended
      and dialysed against phosphate buffer (pH 7.0). This fraction was incubated with
      HRPO, then loaded on the affinity column which was washed, and the labelled
      bispecfic monoclonal antibodies were eluted under mild conditions (borate buffer
      pH 9.0). The effective yield of this bispecific antibody-HRPO complex was 30
      assay plates or 3000 wells. We have also successfully co-purified covalent
      polyclonal-HRPO conjugates and HRPO-labelled streptavidin using a similar
      strategy to obtain enzyme-labelled probes with high specific activities for a
      multitude of applications.

PMID- 11226462
TI  - ELISA for evaluating the incorporation of plasma derived complement split
      products C3b/iC3b into solid-phase immune complexes.
AB  - An ELISA that measures plasma derived complement (C) split-products C3b/iC3b
      deposited on solid-phase immune complexes during C activation is described.
      Plates are coated with BSA, anti-BSA and plasma is added. Deposited C3b/iC3b is
      then detected by biotinylated anti-C3c-antibodies, avidin-alkaline phosphatase
      and para-nitrophenylphosphate. A novel feature is that the assay measures
      residual C activation capacity rather than in vivo generated C activation
      products. The assay was applied to plasma from 250 healthy blood donors. No
      difference in activation capacity of either the alternative (AP) or classical
      pathway (CP) with regard to age or gender was demonstrated. The total coefficient
      of variation was <5.7%. The ELISA procedure was compared to a standard hemolytic
      complement CH(50) assay using plasma from 23 out-patients with systemic lupus
      erythematosus (SLE). There was a weak correlation between the two assays for both
      C pathways, but neither the ELISA nor the CH(50) assay showed any correlation
      with the diagnostic ACR-criteria for SLE. However, the capacity of the CP was
      significantly reduced in SLE out-patients compared to healthy blood donors
      (P<0.0001).

PMID- 11226463
TI  - Low serum conditions for in vitro generation of human macrophages with macrophage
      colony stimulating factor.
AB  - Animal serum is often used to generate human macrophages in vitro. Since fetal
      calf serum (FCS) may complicate antigen uptake, processing and presentation on
      HLA molecules, we tested the ability of M-CSF to generate macrophages at low
      fetal calf serum conditions. Peripheral blood monocytes from 12 individuals were
      cultured 1-4 days with 0-100 ng/ml macrophage colony stimulating factor (M-CSF)
      at either 1 (low) or 5% (v/v) FCS. Regardless of number of days in culture,
      maximal (50-100 ng/ml) M-CSF stimulation and low FCS induced 65+/-5% esterase
      positive cells in all individuals compared to 52+/-7% without M-CSF (P<0.001). M
      CSF increased the mean proportion of esterase positive cells after 24 or 96 h by
      13% (P<0.005) and 13% (P<0.005), respectively, in 1% FCS, and 8% (P<0.05) and 2%
      (NS), respectively, in 5% FCS, indicating a slight negative interaction between
      5% FCS and M-CSF (P<0.05). All cells were positive for CD14 and HLA class II, but
      cell number did not increase, confirming that M-CSF promote macrophage
      differentiation also at low FCS. M-CSF increased the average cell size after 24
      or 96 h by 5.9+/-1.0 (P<0.05) and 8.6+/-0.5 (P<0.001) microm, respectively,
      without an increase in 5% FCS, further demonstrating the efficiency of M-CSF to
      promote macrophage generation at low FCS. The culture supernatants were negative
      for IL-1beta and TNF-alpha, which demonstrates that M-CSF did not activate the
      macrophages. The generation of human macrophages by M-CSF at low FCS should prove
      useful in studies where higher FCS concentrations may interfere with the assay.

PMID- 11226464
TI  - Ex vivo induction of cytokine mRNA expression in human blood samples.
AB  - The interest in the quantitative analysis of cytokine mRNA profiles has increased
      substantially in recent years. This is based on the potential use of basal
      cytokine mRNA expression as sensitive markers for in vivo lymphocyte activation
      in a variety of clinical settings. However, it is less well known to what extent
      differences in blood collection and preparation techniques may cause ex vivo
      alteration of quantitative cytokine mRNA levels. We therefore evaluated the
      effect of blood sampling and the impact of cell separation on interleukin (IL)-2,
      IL-4, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha mRNA
      expression in an intraindividual study design (n=8). Two different blood sampling
      procedures were applied. A whole blood sample 1 was collected by constant
      moderate blood flow into a blood collection tube containing lithium-heparin.
      Moreover, a second sample from the same donor was collected by a 5-fold
      acceleration of blood flow. Furthermore, peripheral blood mononuclear cell (PBMC)
      were isolated from the first whole blood sample by density separation over Ficoll
      Hypaque. The quantification of cytokine mRNA expression was performed by real
      time PCR in native whole blood/PBMC samples or unstimulated cultures. We found a
      significant increase of IL-2, IL-4 and TNF-alpha mRNA expression (P=0.018,
      P=0.028, P=0.018) in whole blood samples collected by rapid sampling. The
      isolation of PBMC by density gradient separation prompted on upregulation of the
      mRNA levels of IL-2, IL-4 and TNF-alpha 5-9-fold (P=0.018, P=0.018, P=0.018). In
      contrast, IFN-gamma mRNA expression was not significantly influenced by
      differences in blood sample preparation. Our data clearly demonstrate that
      differences in the blood sampling technique or cell separation should be
      considered as important factors for non-physiological ex vivo induction of
      cytokine mRNA expression. The current data emphasize the need for data on the
      impact of ex vivo variation in order to extract reliable and consistent
      information, particularly when cytokine mRNA expression data from healthy blood
      donors are included in clinical studies.

PMID- 11226465
TI  - Controlling duration of contact between T cells and antigen-presenting cells.
AB  - A new method which allows precise control of the duration of contact between T
      cells and antigen-presenting cells (APCs) has been developed. A glass coverslip
      coated with poly-L-lysine, and then with T cells, was placed at the base of a
      cylindrical well, and the well was filled with liquid medium. A round coverslip,
      on which APCs were adhered, was supported on the surface of the medium by surface
      tension, cell-side down. By withdrawing medium from four capillary holes near the
      base of the well, the coverslip could be lowered to initiate contact between T
      cells and APCs at a defined time zero. The contact was broken at desired time
      points by re-introducing medium into the well in order to separate the two
      coverslips. Each cell type remained adherent to its original surface after
      separation for all contact times studied. The T cells were monitored for
      intracellular calcium mobilization using the fluorescent dye, Fura-2. Contact
      durations of less than 1 min did not trigger calcium signals. Contact durations
      of 3 and 5 min induced strong calcium signals. Breaking the contact caused a
      rapid decrease in intracellular calcium levels. This method of cell manipulation
      allows precise control of the duration of contact of T cells with APCs, while
      keeping the cells under continuous observation. The measurements so obtained
      provide a quantitative understanding of the dynamics of early T cell activation.

PMID- 11226466
TI  - Microminiaturized immunoassays using quantum dots as fluorescent label by laser
      confocal scanning fluorescence detection.
AB  - An immunoassay readout method based on fluorescent imaging analysis with laser
      confocal scanning is described. The ZnS-coated CdSe quantum dots (ZnS/CdSe QDs)
      were linked to a detection antibody. Immunoassay was carried out on a glass chip
      using a sandwich assay approach, where antibody covalently bound to a glass chip
      was allowed to capture antigen specially. Afterwards, the detection antibody
      labeled with QD was allowed to bind selectively to the captured antigen. The
      fluorescent signals of the sandwich conjugate were detected by a laser confocal
      scanner. A diode laser was used to excite efficiently the fluorescent signals
      while bovine serum albumin was used to eliminate nonspecific binding sites. The
      detection limit of this approach was up to 10(-9) M under current experimental
      conditions. The specificity of the QDs-labeled immunoglobulin (IgG) was tested by
      an experiment using goat IgG and human IgG samples. The result was consistent
      with the binding specificity in a sandwich-type assay. The potential of this
      method to function as a simple and efficient readout strategy for immunoassay in
      biochip is discussed.

PMID- 11226467
TI  - Sepharose-unbinding ricin E as a source for ricin A chain immunotoxin.
AB  - To evaluate the Sepharose-unbinding ricin E as a preference source material for
      ricin A chain (RTA) in immunotoxin studies, RTA of ricin E (RTA(E)) was
      characterized and compared with RTA of the Sepharose-binding ricin D (RTA(D)).
      RTA(E) and RTA(D) were separated into two subunits of A(1) and A(2) by capillary
      electrophoresis. The isoelectric points of A(1) and A(2) subunits were determined
      to be 7.6 and 7.4, respectively, for RTA(E), while they were 7.4 and 7.3,
      respectively, for RTA(D). The molecular masses of A(1) and A(2) isomers
      determined by the matrix-assisted laser desorption ionization time-of-flight
      (MALDI-TOF) mass spectrometry were 31059 and 32266 Da, respectively, for RTA(E),
      while they were 30892 and 32179 Da, respectively, for RTA(D). There were no
      significant differences in the cell surface affinity and cytotoxicity between
      RTA(E) and RTA(D). Anti-CD4-RTA(E) immunotoxin was prepared by conjugating RTA(E)
      with anti-CD4 monoclonal antibody using a heterobifunctional crosslinker, 4
      succinimidyl-oxycarbonyl-alpha-methyl-alpha-(2-pyridyldithio) toluene. Anti-CD4
      RTA(E) immunotoxin showed comparable cytotoxic effects to anti-CD4-RTA(D)
      immunotoxin to antigen-positive CEM cells in vitro. It is concluded that RTA(E)
      from ricin E is one of different variants of RTA(D) and may be used as a
      preference source material of RTA in immunotoxin studies.

PMID- 11226468
TI  - A novel technique for the fluorometric assessment of T lymphocyte antigen
      specific lysis.
AB  - The 51Cr release assay has traditionally been used to investigate effector cell
      cytotoxic function against labeled targets, but this method has inherent problems
      that include hazards associated with radioactivity, cell labeling and high
      spontaneous release. Here we describe a novel flow cytometric assay which
      addresses and improves upon the problems currently encountered with the 51Cr
      release assay. The fluorometric assessment of T lymphocyte antigen specific lysis
      (FATAL) assay employs dual staining (PKH-26 and CFSE) to identify and evaluate
      the target population. We found that the PKH-26/CFSE combination efficiently
      labeled target cells. Evaluation of the spontaneous leakage from dye labeled
      target cells was forty fold lower than the spontaneous leakage seen with the 51Cr
      release assay. The FATAL assay permitted a more accurate assessment of the
      effector: target ratio, and detected low levels of cytotoxic T lymphocyte (CTL)
      mediated lysis. There was a strong correlation between the 51Cr release and FATAL
      assays, when performed in parallel with identical effector and target cells
      (r(2)=0.998, P=<0.0001). This novel method of detecting cytolysis represents a
      qualitative and quantitative improvement over standard 51Cr release analysis. The
      FATAL assay will be of value to further investigate mechanisms of cytolysis by
      effector cell populations.

PMID- 11226469
TI  - Activation of antigen-specific T cells by artificial cell constructs having
      immobilized multimeric peptide-class I complexes and recombinant B7-Fc proteins.
AB  - T cell activation results from the engagement of multiple receptors on T cells by
      their respective ligands on antigen presenting cells. Studies using artificial
      cell surface constructs have demonstrated that effective T cell response requires
      that antigen be presented on a solid surface with dimensions that approximate
      those of an intact cell. In this report, we describe the cloning and expression
      of recombinant B7-1-Fc and B7-2-Fc proteins and their incorporation onto 5-microm
      latex microspheres along with renatured peptide-MHC. These microspheres provide a
      simple and effective method for the in vitro or in vivo stimulation of antigen
      specific T cells under precisely controlled antigen and costimulation conditions.

PMID- 11226470
TI  - Characterization of cytohesin-1 monoclonal antibodies: expression in neutrophils
      and during granulocytic maturation of HL-60 cells.
AB  - ADP-ribosylation factors (Arf) are small GTP-binding proteins involved in
      vesicular transport and the activation of phospholipase D (PLD). The conversion
      of Arf-GDP to Arf-GTP is promoted in vivo by guanine nucleotide exchange factors
      such as ARNO or cytohesin-1. In order to examine the expression of ARNO and
      cytohesin-1 in human granulocytes, we generated specific polyclonal and
      monoclonal antibodies (mAbs). We also overexpressed GFP-ARNO and GFP-cytohesin-1
      in RBL-2H3 cells to characterize the specificity and the ability of cytohesin-1
      mAbs to immunoprecipitate cytohesin-1. Among the hybridomas secreting cytohesin-1
      mAbs, only the clones 2E11, 1E4, 3C8, 6F5, 4C7, 7A3 and 8F7 were found to be
      specific for cytohesin-1. Furthermore, mAb 2E11 immunoprecipitated GFP-cytohesin
      1 but not GFP-ARNO under native conditions. In contrast, mAbs 5D8, 4C3, 2G8,
      6G11, 4C3, 6D4, 7B4 and 6F8 detected both cytohesin-1 and ARNO as monitored by
      immunoblotting. Although mAb 6G11 detected both proteins, this antibody
      immunoprecipitated GFP-ARNO but not GFP-cytohesin-1 under native conditions.
      Another antibody, mAb 10A12, also selectively immunoprecipitated GFP-ARNO under
      native conditions, but the epitope recognized by this mAb is unlikely to be
      linear as no signal was obtained by immunoblotting. Immunoprecipitation with a
      cytohesin-1 polyclonal antibody and blotting with cytohesin-1 specific mAbs
      revealed that cytohesin-1 is highly expressed in neutrophils. Cytohesin-1 can be
      detected in HL-60 cells but the endogenous protein levels were low in
      undifferentiated cells. Using the specific cytohesin-1 mAb 2E11 we observed a
      marked increase in levels of cytohesin-1 expression during dibutyryl-cyclic AMP
      induced granulocytic differentiation of HL-60 cells. These data suggest that
      cytohesin-1, which may have important functions in neutrophil physiology, can be
      useful as a potential marker for granulocytic differentiation.

PMID- 11226471
TI  - Single epitope multiple staining to detect ultralow frequency B cells.
AB  - Here we describe a method for detecting ultralow frequency target cells from
      within a high background of irrelevant cells by a novel method, single epitope
      multiple staining (SEMS). Samples of murine splenocytes were seeded with a low
      number of splenocytes from mice transgenic for a hen eggwhite lysozyme (HEL)
      specific immunoglobulin (Ig). These samples were stained with two reagents
      specific for the same epitope expressed by the transgenic B cells, which had been
      conjugated to two different detectable labels (FITC and biotin). This dual
      staining of a single epitope allowed us to reduce the background due both to non
      specific binding of reagents and to probabilistic distribution of the cells. We
      also were able to detect the cells based on knowing only one thing about them,
      namely, their antigen specificity. The SEMS method allowed us to reproducibly
      detect transgenic cells at frequencies below one cell in one million cells. SEMS
      could be used to increase the sensitivity of numerous fluorescence-based
      applications in addition to the detection and isolation of antigen-specific
      lymphocytes, including the detection and highly specific isolation of genetically
      modified cells, transformed cells, stem cells, fetal cells, or infectious
      organisms.

PMID- 11226472
TI  - Generation of high titer antisera in rabbits by DNA immunization.
AB  - Mesothelin is a GPI-linked, membrane-associated differentiation antigen that is
      over-expressed in several forms of human cancers. Intradermal injection into
      rabbits of plasmid DNA encoding full length mesothelin resulted in antisera with
      titers as high as 1:100,000. Each immunization consisted of 320 microg of DNA
      delivered into 4 sites. After the initial three injections antisera titers were
      moderate (between 10 to 30,000) and fell over the course of about 7 weeks. When
      the titers had fallen, an injection of a booster dose of DNA resulted in very
      high titers of antisera. These antisera contained IgGs that could bind to both
      recombinant mesothelin made in Eschericha coli and to mesothelin present on human
      cells in Western blots and in immunofluorescence assays. These observations
      indicate that simple intradermal DNA immunization of rabbits can result in high
      titers of antibodies that can be used for a variety of purposes.

PMID- 11226473
TI  - Novel multi-probe RNase protection assay (RPA) sets for the detection of murine
      chemokine gene expression.
AB  - Chemokines play an essential role in immune and inflammatory reactions via the
      recruitment of leukocytes. Studying the role of chemokines in vivo is complicated
      by the redundancy of their action and by their promiscuous receptor usage. The
      simultaneous analysis of several chemokines is, therefore, advantageous in order
      to obtain a comprehensive view of chemokine participation in inflammatory and
      infectious processes. At present, no multi-probe detection systems are available
      for the analysis of recently described chemokines. In this study, new multi-probe
      RNase protection assay (RPA) template sets were developed for the analysis of
      murine chemokines. Chemokine cDNA fragments were generated by RT-PCR and
      individually subcloned into the plasmid pGEM-T providing a T7 promotor. In this
      way, two multi-probe template sets were constructed each containing six chemokine
      sequences (CXCL12/SDF-1, XCL1/lymphotactin, CCL20/exodus-1, CCL25/TECK,
      CX3CL1/fractalkine, CXCL1/KC, and CCL20/MDC, CXCL9/MIG, CCL9/10/MIP-1gamma,
      CXCL13/BLC, CCL12/MCP-5, CCL19/ELC, respectively) and templates for the two house
      keeping genes L32 and GAPDH. The evaluation of these RPA template sets in various
      murine models demonstrated their suitability for the analysis of the above
      chemokines both under constitutive and infection-induced conditions. To reduce
      the personal radiation hazard, we found that 32P could be replaced by 33P without
      any loss of assay-sensitivity. These new RPA multi-probe sets provide valuable
      tools for the simultaneous quantitative determination of gene expression of
      multiple murine chemokines of both constitutive and inducible type.

PMID- 11226474
TI  - A panel immunoblot using co-incubated monoclonal antibodies for identification of
      melanoma cells.
AB  - Antigen expression in melanoma is heterogeneous. Immunophenotyping using a panel
      of monoclonal antibodies may facilitate immunotherapy. An immunoblot procedure
      was developed to detect antigens in melanoma cells. Numerous monoclonal
      antibodies were tested to determine if (1) antigens were detected after transfer
      to membranes, (2) single bands or discrete multiple bands were obtained, (3) co
      incubation of multiple monoclonal antibodies had no interference, and (4) banding
      patterns were non-overlapping. Antigens were selected based upon their
      association with melanoma and the availability of respective monoclonal
      antibodies. Antigens were melanoma antigen recognized by T-cells (MART-1),
      tyrosinase, tyrosinase-related protein 1 (TRP-1), S100, vimentin, glycoprotein
      130 (gp130), a carcinoembryonic antigen (CEA)-like marker, KBA-62 and NKI-C3.
      Actin positive controls could be assessed simultaneously. Test samples were
      separated by polyacrylamide gel electrophoresis in a 4-15% polyacrylamide
      gradient, transferred to polyvinylidine fluoride membrane, blotted using a Fast
      Blot apparatus (Pierce), and developed using diaminobenzidine/metal. Melanoma
      cell lines were immunophenotyped using this panel immunoblot, and were compared
      to a standard control and to non-melanoma cells. Up to four antigens could be
      detected simultaneously in a single lane of the immunoblot, using a single test
      sample of greater than 100000 cells.

PMID- 11226475
TI  - New method for detection of Borrelia burgdorferi antigen complexed to antibody in
      seronegative Lyme disease.
AB  - Serologic tests for Lyme disease are problematic. Because of cross-reactive
      antigens Borrelia burgdorferi (Bb) shares with other organisms, Lyme disease can
      be overdiagnosed. However, in addition to specificity problems, serologic tests
      for early Lyme disease can be falsely negative due to lack of sensitivity of
      ELISAs and Western blots. Most routine antibody tests are designed to detect free
      antibodies, and in early, active disease, circulating antibodies may not be free
      in serum but sequestered in complexes with the antigens which originally
      triggered their production. This difficulty may be overcome by first isolating
      immune complexes (IC) from the serum and using this fraction for testing. Free
      Borrelia-specific antibodies can then be liberated from the immune complexes
      which may enhance test sensitivity in patients with active disease. We developed
      a technique that captures the antibody component of IC on immunobeads, and
      subsequently releases the antigen component of IC. Immunoblotting with monoclonal
      antibody detected at least one antigen to be OspA, thus definitively
      demonstrating a Borrelia-specific antigen in circulating IC in early Lyme
      disease. This test is also useful in demonstrating Bb antigen in otherwise
      seronegative Lyme disease patients.

PMID- 11226476
TI  - Determination of cytokine regulatory haplotypes by induced heteroduplex analysis
      of DNA.
AB  - Multiple single nucleotide polymorphisms (SNP) in the promoter region of the
      human interleukin-10 (IL-10) gene and in the signal/leader sequence of the human
      transforming growth factor beta 1 (TGF-beta1) gene, have been associated with
      susceptibility, severity and clinical outcome for a number of diseases. One
      common explanation for this, is that different haplotypes of these SNPs regulate
      the expression of the respective cytokines. Therefore, accurate determination of
      haplotypes by physical linkage analysis represents an important tool in
      investigating the pathogenesis of such diseases. Here, we demonstrate that the
      use of induced heteroduplex generators (IHGs) may be used to identify haplotypes
      within target sequences in the IL-10 and TGF-beta1 genes. Four haplotypes were
      observed within the IL-10 promoter region, consisting of -1082, -851, -819 and 
      592 SNPs. For the TGF-beta1 signal/leader sequence, we observed three haplotypes
      of the T869C (Leu10Pro) and G915C (Arg25Pro) SNPs. In both cases, all
      combinations of these haplotypes could be resolved unequivocally with a single
      IHG reagent.

PMID- 11226477
TI  - An improved anti-C3/IgG ELISA for quantification of soluble immune complexes.
AB  - A semi-quantitative ELISA for complement-fixing, IgG-containing immune complexes
      (IC) is described. The assay is based on the insolubilization of IC by
      polyethyleneglycol, their capture by solid-phase anti-C3 antibodies, reaction
      with peroxidase-labeled anti-IgG antibodies and incubation with a chromogenic
      peroxidase substrate. It was markedly improved by the use of a single-step
      procedure which simultaneously washed and precipitated the insolubilized immune
      complexes. Intra-assay and inter-assay coefficients of variation were lower than
      8.6 and 14.7%, respectively. As expected, higher levels of circulating immune
      complexes, in relation to healthy individuals, were found in patients with
      American visceral leishmaniasis (AVL), systemic lupus erythematosus (SLE) and
      rheumatoid arthritis (RA), with prevalences comparable to those described in the
      literature. The ELISA can be quickly assembled from reagents and plasticware
      widely available commercially, detects immune complexes fulfilling three
      different criteria and is more sensitive than a previously published method based
      on the same principles (detection limit for complement-sensitized aggregated IgG
      of 2 microg ml(-1) as compared with a detection limit above 16 microg ml(-1)).

PMID- 11226479
TI  - Quantitative analysis of specific mRNA species in minute cell samples by RT-PCR
      and flow cytometry.
AB  - A method for the quantitative determination of specific mRNAs in small numbers of
      cells, freshly isolated from tissues or early cell cultures, was developed by
      combining quantitative reverse transcription-polymerase chain reaction (RT-PCR)
      and quantitative flow cytometry. Freshly isolated umbilical vein endothelial
      cells were sorted by flow cytometry and then lysed. The number of cells in the
      lysate was determined by counting of nuclei after propidium iodide staining using
      flow cytometry. The number of plasminogen activator inhibitor-1 (PAI-1) mRNA
      copies per cell was determined by quantitative RT-PCR using point-mutated PAI-1
      cRNA as an internal standard. The cells were shown to contain 400-900 copies of
      PAI-1 mRNA molecules per cell which confirms that endothelial cells in vivo
      express PAI-1. PAI-1 mRNA expression was also analyzed in small numbers of
      endothelial cells in primary culture in basal conditions and after incubation
      with different interleukins. The method allowed reliable and reproducible
      estimation of the number of mRNA copies per cell from original cell samples
      containing less than 1000 cells. This method can be used for the quantitative
      determination of various mRNA species in specified cell populations from small
      tissue samples or cultured cells.

PMID- 11226478
TI  - Quantitative single cell methods that identify cytokine and chemokine expression
      in dendritic cells.
AB  - Two techniques based upon flow cytometry (FCM) and in situ image analysis were
      developed for quantification of intracellular cytokine and chemokine protein
      expression at the single cell level in dendritic cells (DCs). The qualitative and
      quantitative differences between the two methods were evaluated. In vitro
      differentiated DCs were stimulated with lipopolysaccaride (LPS) and thereafter
      stained for either IL-8, which is secreted through the Golgi-organelle, or IL
      1ra, which localises diffusely in the cytoplasm. Microscopic examination, both
      for fluorophore and enzymatically stained cells, showed that DCs expressed IL-8
      and IL-1ra with two different staining patterns. FCM analysis showed high
      frequencies of IL-1ra producing cells (76+/-13%), which was similar to the
      frequency obtained by in situ imaging. However, in contrast to IL-1ra, the
      incidence of IL-8 expressing DCs showed high variability between the donors. The
      numbers of positive cells were 19+/-19% as measured by FCM. The detection of IL-8
      analysed by in situ imaging revealed higher frequencies (26+/-14%). The addition
      of brefeldin-A, leading to cytoplasmic accumulation of proteins secreted through
      the Golgi endoplasmatic route, generated a significantly increased signal
      intensity and incidence of producer cells, resulting in similar frequencies for
      both methods. FCM has the advantage of being less time consuming than image
      analysis and is also able to facilitate multiple colour analysis. However, FCM is
      less accurate in detecting and quantifying cytokines and chemokines with a
      preserved juxtanuclear staining pattern. The correct choice of detection
      technique therefore depends on the study question.

PMID- 11226480
TI  - Validation of an Mx/CAT reporter gene assay for the quantification of bovine type
      I interferon.
AB  - We describe here a specific and sensitive assay for biologically active bovine
      type-I interferon (IFN) in an Mx/CAT reporter gene assay. The assay is based on
      Madin-Darby Bovine Kidney cells transfected with a plasmid, containing a human
      MxA promoter driving a chloramphenicol acetyltransferase (CAT) cDNA. CAT
      expression was quantified in a commercially available enzyme linked immunosorbant
      assay. The response to recombinant bovine INF-alpha(1) was dose dependent between
      0.25 and 125.0 iu/ml and was shown to be specific for type-I IFN as no
      significant effect was seen with a number of other cytokines, including IFN
      gamma. This Mx/CAT reporter assay also has advantages in terms of simplicity and
      reliability over conventional cytopathic effect reduction assays used to quantify
      the IFN activity in bovine samples. The Mx/CAT reporter assay was used
      successfully to measure trophoblast derived type-1 IFN activity (IFN-tau) in
      uterine flushings collected from pregnant cows. IFN-tau is the pregnancy
      recognition signal produced in ruminants by pre-implantation embryos and was
      shown to increase markedly between the 12th (0.7+/-0.14 iu/ml) and 18th
      (44085.0+/-14414.2 iu/ml) day of pregnancy. In contrast, IFN-tau activity
      remained basal (0.5-0.7 iu/ml) in inseminated non-pregnant animals. Duplicate
      samples analysed using a cytopathic effect reduction assay correlated well
      (P<0.001; r(2)=0.945) with IFN levels obtained using the Mx/CAT reporter assay,
      confirming the reporter assay as a reliable substitute for the standard anti
      viral IFN assay.

PMID- 11226481
TI  - Multiplex screening for functionally rearranged immunoglobulin variable regions
      reveals expression of hybridoma-specific aberrant V-genes.
AB  - Modification of antibody effector functions is commonly performed by
      chimerization or humanization. Cloning of antibody variable regions from
      hybridomas represents a first step that is frequently hampered by the expression
      of non-functionally rearranged variable regions in hybridoma cells that originate
      from MOPC21-derived fusion partners. We now present a simple method to clone
      functionally rearranged V-genes, based on V-gene-specific multiplex PCR
      screening. Using this method we document the expression of aberrant V-genes that
      originate from the original B-cell used for the hybridoma generation, not from
      the fusion partner, and are - thus - hybridoma specific.

PMID- 11226500
TI  - Study of colour discrimination with comb-filtered spectra.
AB  - Techniques that involve the use of comb-filtered spectra to study human colour
      vision have been developed in previous work (Bonnardel, V., Bellemare, H.,
      Mollon, J.D., 1996. Measurements of human sensitivity to comb-filtered spectra,
      Vision Research 36, 2713-2720; Bonnardel, V., Ruderman D.L., Barlow, H.B., 1997.
      A fast determination of the Spectral Modulation Sensitivity Function: a
      comparison between trichromats and deuteranopes. In: C.R. Cavonius (ed.), Color
      vision deficiencies XIII. Dordrecht: Kluver 415-424). These techniques are
      applied in the present study to measure colour discrimination among
      deuteranomalous observers and normal trichromats, with the aim of determining the
      spectral position of the anomalous cone fundamentals. Results show that comb
      filtered spectra are useful in determining the extent to which variability in
      colour discrimination among anomalous and normal trichromatic colour observers is
      accounted for by the spectral properties of photoreceptors.

PMID- 11226482
TI  - Delineation of a linear epitope by multiple peptide synthesis and phage display.
AB  - Two different approaches, the phage display technique and the Spot peptide
      synthesis on cellulose membranes, were used to identify sequences recognized by
      Fab 57P, specific for tobacco mosaic virus protein (TMVP), and define the
      preferred chemical composition of a functional epitope. Kinetic measurements of
      the interaction between peptide variants and the antibody fragment were used to
      further refine the molecular basis of binding activity. Our results show that the
      functional epitope of Fab 57P requires precise physico-chemical properties at a
      limited number of positions, and that residues flanking these key residues can
      influence binding affinity. The phage display and Spot synthesis methods allowed
      the straightforward localization of the binding region and the identification of
      residues that are essential for recognition. However, these methods yielded
      slightly different views of accessory factors that are able to influence antibody
      binding. The influence on binding activity of these factors can only be assessed
      through quantitative affinity measurements.

PMID- 11226501
TI  - The development of the crystalline lens is sensitive to visual input in the
      African cichlid fish, Haplochromis burtoni.
AB  - We investigated whether the development of the vertebrate crystalline lens is
      sensitive to visual input. The optical properties of fish lenses were examined as
      a function of lens size and the optical rearing conditions. Fish (Haplochromis
      burtoni, Cichlidae) were reared in white light (control group), under spectral
      deprivation (monochromatic lights), deprivation of the cone system (scotopic
      illumination), and complete visual deprivation (darkness). Longitudinal spherical
      aberrations (LSAs) and refractive index profiles of the lenses were measured with
      thin laser beams. The performance of the lens was modeled by ray-tracing
      calculations from measured LSAs. In lenses from the control group, LSA and f/R
      (focal length relative to lens radius) decreased as a function of age. The
      optical properties of the lenses were modified after rearing in darkness,
      scotopic illumination, and in monochromatic lights due to changes in the
      refractive index profile. Rearing in darkness and scotopic illumination reduced
      the optical quality of the lens. In animals reared under spectral deprivation,
      the lens did not create well-focused images for all spectral cone types in the
      same plane, as it does in animals reared in white light. We conclude that visual
      input seems to play an important role in the development of the lens. The control
      mechanisms remain unknown.

PMID- 11226502
TI  - A motion aftereffect seen more strongly by the non-adapted eye: evidence of
      multistage adaptation in visual motion processing.
AB  - We found that the motion aftereffect measured using a directionally ambiguous
      counterphase grating (flicker MAE) can be stronger when it is measured for the
      non-adapted eye than when measured for the adapted eye. The monocularly viewed
      adaptation stimulus was the movement of a missing-fundamental grating (2f+3f
      motion), for which the movement of the higher-order spatial structure was
      dominantly perceived, while the first-order structure was physically moving in
      the opposite direction. For observers who perceived the MAE consistently in the
      direction opposite to the movement of the higher-order structures, the MAE was
      larger for the non-adapted eye than for the adapted eye. This finding of 'over
      100% transfer' invalidates the standard view that the IOT is a direct measure of
      the binocularity of the adapted neurones. In addition, the finding provides
      convincing support for the hypothesis that the flicker MAE reflects adaptation at
      multiple processing stages

PMID- 11226503
TI  - Measurement and modeling of center-surround suppression and enhancement.
AB  - The apparent contrast of a central stimulus is affected by the presence of
      surrounding stimuli. For some stimulus conditions, the apparent contrast is
      suppressed and for other conditions the apparent contrast is enhanced. This
      report is intended to offer a coherent description of the stimulus factors that
      influence suppression and enhancement. Using a contrast-matching protocol, we
      measured the contrast dependence of center-surround interactions by
      systematically varying the suprathreshold contrasts of the central and surround
      gratings. Different spatial configurations of the surround stimuli were studied.
      Our results confirmed previous findings that (1) a surround stimulus could
      produce either contrast enhancement or contrast suppression depending on the
      balance of the central and surround contrasts; (2) suppression varied with the
      width of the surround stimulus and was strongly orientation-specific; and (3)
      enhancement was less sensitive to changes in surround configurations (in
      particular, enhancement did not depend on the colinearity of the central and
      surround gratings). Based on the experimental data, we developed a computational
      model to account for center-surround suppression and enhancement.

PMID- 11226505
TI  - Identification of facial images in peripheral vision.
AB  - Contrast sensitivity for face identification was measured as a function of image
      size to find out whether foveal and peripheral performance would become
      equivalent by magnification. Size scaling was not sufficient for this task, but
      when the data was scaled both in size and contrast dimensions, there was no
      significant eccentricity-dependent variation in the data, i.e. for equivalent
      performance both the size and contrast needed to increase in the periphery. By
      utilising spatial noise added to the images we found that in periphery
      information was utilised less efficiently and peripheral inferiority arose
      completely from lower efficiency, not from increased internal noise.

PMID- 11226504
TI  - Sensitivity to contrast histogram differences in synthetic wavelet-textures.
AB  - Recent research on texture synthesis suggests that characterisation of those
      properties of textures to which human observers are sensitive may be provided by
      the histograms of the coefficients of a wavelet decomposition. In this study we
      examined the properties of wavelet histograms that affect texture discrimination
      by measuring observer sensitivity to differences in the wavelet histograms of
      synthetic textures. The textures, generated via Gabor micropattern synthesis,
      were broadband, with amplitude spectra that are characteristic of natural images,
      i.e. 1/f. We measured texture-difference thresholds for three moments of the
      wavelet histograms -- variance, skew and kurtosis -- by manipulating the
      contrast, phase, and density, of the Gabor elements used to construct the
      textures. Observers discriminated more efficiently between textures that had
      differences in kurtosis, than between textures that had differences in either
      variance or skew. Performance was compared to two model observers; one used the
      pixel-luminance histogram, the other used the histogram of the output of wavelet
      filters. The results support the idea that the visual system is relatively
      sensitive to the kurtosis, or 4th moment, of the wavelet histogram of textures.
      We argue that higher than 4th-order moments will, in practice, become
      increasingly difficult for the visual system to represent because the lack of a
      perfect match between the elements and the receptive fields effectively blurs the
      response histogram, thereby attenuating higher moments.

PMID- 11226506
TI  - Perceptual grouping via spatial selection in a focused-attention task.
AB  - Theories of attention can be separated into those that select by location, and
      those that select by location-invariant representation. Experiments demonstrating
      stronger interference or facilitation from distractors grouped by nonspatial
      features with the target than ungrouped distractors have been considered as
      evidence for the selection of location-invariant representations. However, few
      studies have measured spatial attention directly at the locations of the grouped
      or ungrouped objects. In these experiments subjects responded to spatial probes
      (dots) while also identifying a cued target letter among distractors. Probe
      responses were faster for distractor locations with the target color than for
      those with the nontarget color, implying that target-color locations receive more
      attention. This pattern of spatial attention may explain why target-color
      distractors interfere more with target identification than nontarget-color
      distractors. These results suggest that although attention can be directed by
      nonspatial properties such as grouping by color or organization of the scene into
      objects, selection may ultimately be based on location.

PMID- 11226507
TI  - Disconjugate oculomotor learning caused by feeble image-size inequality:
      differences between secondary and tertiary positions.
AB  - In order to examine the minimum value of image-size inequality capable of
      inducing lasting disconjugacy of the amplitude of saccades, six normal emmetropic
      subjects were exposed for 16 min to 2% image size inequality. Subjects were
      seated at 1 m in front of a screen where a random-dot pattern was projected and
      made saccades of 7.5 and 15 deg along the horizontal and vertical principal
      meridians and to tertiary positions in the upper and lower field. During the
      training period, compensatory disconjugacy of the amplitude of the saccades
      occurred for the principal horizontal and vertical meridians; such increased
      disconjugacy persisted after training, suggesting learning. In contrast, for
      horizontal saccades to or from tertiary positions made in the upper and lower
      field, no consistent changes in the disconjugacy occurred, either during training
      or after the training condition. In an additional experiment, three subjects read
      sequences of words with the 2% magnifier in front of their dominant eye: in such
      a task, horizontal saccades to or from tertiary positions at the upper or lower
      field showed appropriate and lasting disconjugacy for two of the three subjects.
      We conclude that even a 2% image size inequality stimulates oculomotor learning,
      leading to persistent disconjugacy of saccades. The small disparity created by
      the image-size inequality is thus compensated by the oculomotor system rather
      than tolerated by the sensory system (e.g. by enlarging the Panum's area).

PMID- 11226508
TI  - Colour thresholds and receptor noise: behaviour and physiology compared.
AB  - Photoreceptor noise sets an absolute limit for the accuracy of colour
      discrimination. We compared colour thresholds in the honeybee (Apis mellifera)
      with this limit. Bees were trained to discriminate an achromatic stimulus from
      monochromatic lights of various wavelengths as a function of their intensity.
      Signal-to-noise ratios were measured by intracellular recordings in the three
      spectral types of photoreceptor cells. To model thresholds we assumed that
      discrimination was mediated by opponent mechanisms whose performance was limited
      by receptor noise. Most of the behavioural thresholds were close to those
      predicted from receptor signal-to-noise ratios, suggesting that colour
      discrimination in honeybees is affected by photoreceptor noise. Some of the
      thresholds were lower than this theoretical limit, which indicates summation of
      photoreceptor cell signals.

PMID- 11226509
TI  - The role of target position in smooth pursuit deceleration and termination.
AB  - Subjects smoothly pursued a target moving horizontally at 15 deg/s. After pursuit
      for 1 s, the target jumped 3 deg ahead of the fovea. At the moment of the jump,
      target velocity became 0 and 'effective visual feedback' assumed a value of
      either 0 (target retinally stabilized), -0.2, -0.4, or -1.0 (target fixed in
      space). With 0 visual feedback the eye continued to move smoothly at a moderate
      velocity, an apparent response to target position relative to the fovea. When
      negative visual feedback was present eye velocity decreased. With -0.2 and -0.4
      feedback, this decrease was not a simple exponential, but often consisted of an
      initial fast decrease followed by slower decrease. With -1.0 feedback, eye
      velocity quickly decreased in an approximately exponential manner, and stopped.
      We were able to simulate these pursuit responses using a simple model of the
      pursuit system. Key features of the model are: (a) a target-velocity channel
      whose output decreases with target offset from the fovea, and whose gain switches
      from high to low as pursuit velocity approaches zero; (b) a target-position
      channel with a saturation non-linearity at 1-3 deg; and (c) a positive feedback
      loop with gain of less than 1.0. All of these features are essential to simulate
      the pursuit responses, especially with visual feedback values of -0.2 and -0.4.
      Our results and model suggest that target position serves as an important
      stimulus in guiding smooth pursuit as pursuit velocity decreases, and especially
      during pursuit termination.

PMID- 11226511
TI  - The infrared absorption of amino acid side chains.
AB  - Amino acid side chains play fundamental roles in stabilising protein structures
      and in catalysing enzymatic reactions. These fields are increasingly investigated
      by infrared spectroscopy at the molecular level. To help the interpretation of
      the spectra, a review of the infrared absorption of amino acid side chains in
      H(2)O and 2H(2)O is given. The spectral region of 2600-900cm(-1) is covered.

PMID- 11226510
TI  - Contrast discrimination deficits in retinitis pigmentosa are greater for stimuli
      that favor the magnocellular pathway.
AB  - Luminance contrast discrimination was measured in 14 patients with retinitis
      pigmentosa (RP) and 14 control observers with normal vision, using steady
      pedestal and pulsed-pedestal paradigms [Pokorny, J., & Smith, V. C. (1997).
      Psychophysical signatures associated with magnocellular and parvocellular pathway
      contrast gain. Journal of the Optical Society of America A, 14, 2477-2486] to
      bias performance toward the magnocellular (MC) or parvocellular (PC) pathway,
      respectively. The aim was to determine the relative effects of retinal
      degeneration on MC- and PC-pathway function in RP. For five of the RP patients,
      contrast discrimination thresholds were within normal limits for both the steady
      pedestal and pulsed-pedestal paradigms. The other nine RP patients showed
      threshold elevations for the steady-pedestal paradigm (presumed magnocellular
      mediation), whereas their thresholds for the pulsed-pedestal paradigm (presumed
      parvocellular mediation) were within normal limits for all but the two patients
      who had the most extreme threshold elevations using the steady-pedestal paradigm.
      A control experiment on four of the RP patients, using a greater number of
      pedestal contrasts, verified that the patients' thresholds for the pulsed
      pedestal paradigm showed the pattern expected for contrast discrimination
      mediated by the PC pathway. The higher threshold elevations for the steady
      pedestal paradigm than for the pulsed-pedestal paradigm indicate that the retinal
      degeneration that occurs in RP predominantly disrupts contrast discrimination
      under stimulus conditions that favor the MC pathway.

PMID- 11226512
TI  - Chloride in smooth muscle.
AB  - Interest in the functions of intracellular chloride expanded about twenty years
      ago but mostly this referred to tissues other than smooth muscle. On the other
      hand, accumulation of chloride above equilibrium seems to have been recognised
      more readily in smooth muscle. Experimental data is used to show by calculation
      that the Donnan equilibrium cannot account for the chloride distribution in
      smooth muscle but it can in skeletal muscle. The evidence that chloride is
      normally above equilibrium in smooth muscle is discussed and comparisons are made
      with skeletal and cardiac muscle. The accent is on vascular smooth muscle and the
      mechanisms of accumulation and dissipation. The three mechanisms by which
      chloride can be accumulated are described with some emphasis on calculating the
      driving forces, where this is possible. The mechanisms are chloride/bicarbonate
      exchange, (Na+K+Cl) cotransport and a novel entity, "pump III", known only from
      own work. Their contributions to chloride accumulation vary and appear to be
      characteristic of individual smooth muscles. Thus, (Na+K+Cl) always drives
      chloride inwards, chloride/bicarbonate exchange is always present but does not
      always do it and "pump III" is not universal. Three quite different biophysical
      approaches to assessing chloride permeability are considered and the calculations
      underlying them are worked out fully. Comparisons with other tissues are made to
      illustrate that low chloride permeability is a feature of smooth muscle. Some of
      the functions of the high intracellular chloride concentrations are considered.
      This includes calculations to illustrate its depolarising influence on the
      membrane potential, a concept which, experience tells us, some people find
      confusing. The major topic is the role of chloride in the regulation of smooth
      muscle contractility. Whilst there is strong evidence that the opening of the
      calcium-dependent chloride channel leads to depolarisation, calcium entry and
      contraction in some smooth muscles, it appears that chloride serves a different
      function in others. Thus, although activation and inhibition of (Na+K+Cl)
      cotransport is associated with contraction and relaxation respectively, the
      converse association of inhibition and contraction has been seen. Nevertheless,
      inhibition of chloride/bicarbonate exchange and "pump III" and stimulation of
      (K+Cl) cotransport can all cause relaxation and this suggests that chloride is
      always involved in the contraction of smooth muscle. The evidence that (Na+K+Cl)
      cotransport more active in experimental hypertension is discussed. This is a
      common but not universal observation. The information comes almost exclusively
      from work on cultured cells, usually from rat aorta. Nevertheless, work on smooth
      muscle freshly isolated from hypertensive rats confirms that (Na+K+Cl)
      cotransport is activated in hypertension but there are several other differences,
      of which the depolarisation of the membrane potential may be the most
      important.Finally, a simple calculation is made which indicates as much as 40% of
      the energy put into the smooth muscle cell membrane by the sodium pump is
      necessary to drive (Na+K+Cl) cotransport. Notwithstanding the approximations in
      this calculation, this suggests that chloride accumulation is energetically
      expensive. Presumably, this is related to the apparently universal role of
      chloride in contraction.

PMID- 11226513
TI  - AC133 expression on acute myeloid leukemia blasts: correlation to FAB and to CD34
      expression and possible implications for peripheral blood progenitor cell purging
      in AML.
AB  - AC133 is an antigen expressed on CD34+ hematopoietic progenitor cells. In acute
      myeloid leukemia (AML) it is expressed on leukemic blasts of most FAB subtypes.
      However, few data are available regarding coexpression of other surface antigens.
      We measured AC133 expression on AML blasts from 28 consecutive patients at
      initial diagnosis (n=26) or at diagnosis of first relapse (n=2) and on 26
      leukapheresis products from 14 patients. In AML AC133 correlated with CD34
      expression (Spearman r=0.4711, P=0.0114) and even stronger with combined
      CD34/CD33 expression (Spearman r=0.5083, P=0.0068). In leukapheresis products
      AC133 expression correlated with CD34 expression (Spearman r=0.7495, P=0.002) and
      the yield of the obtained amount of CD34+ cells (Spearman r=0.6484, P=0.0121). In
      conclusion AC133 expression is closely related to CD34 expression in AML. In
      leukapheresis products AC133 provides an additional marker for selection of PBPC
      autografts in AC133- AML.

PMID- 11226514
TI  - Masked monosomy 7 in myelodysplastic syndromes is uncommon and of undetermined
      clinical significance.
AB  - Masked monosomy 7, i.e. detected by FISH but not by conventional cytogenetics,
      has been reported in varying frequency in MDS. To establish the prevalence and
      possible clinical significance of the aberration, we studied the 123 previously
      karyotyped MDS patients using FISH and a DNA probe specific for chromosome 7.
      Metaphase cytogenetics revealed ten patients (8%) with monosomy 7 (6 RAEB and 4
      RAEB-t). FISH confirmed this result and detected four more cases (4%) with masked
      monosomy 7 (3 RA and 1 RARS). Thus, masked monosomy 7 is less common than has
      been suggested, and does not seem to carry the same prognostic weight as monosomy
      7 diagnosed by metaphase cytogenetics.

PMID- 11226515
TI  - Flow cytometric analysis of aberrant antigen expression of blasts using CD45
      blast gating for minimal residual disease in acute leukemia and high-risk
      myelodysplastic syndrome.
AB  - To evaluate the availability of quantification of blasts with aberrant antigen
      expression (AAE) using CD45 gating for minimal residual disease (MRD), 15
      patients with acute leukemia (AL) and myelodysplastic syndrome (MDS) were
      studied. In patients with complete remission (CR), the frequency of blasts with
      AAE (%AAE) by CD45/side scatter (SSC) gating was significantly higher than that
      by the traditional forward scatter (FSC)/SSC combination (median, 4.1 vs. 0.3%,
      P<0.0001). We also demonstrated two representative cases, in which leukemia
      relapse could be predicted before 3 weeks and the early treatment for MRD could
      be performed for MRD after allogeneic bone marrow transplantation (BMT). These
      results indicate that this procedure is very useful for the evaluation of the
      quality of CR.

PMID- 11226517
TI  - Commentary: dose intensive chemotherapy in acute myeloid leukemia.

PMID- 11226516
TI  - Combination chemotherapy utilizing continuous infusion of intermediate-dose
      cytarabine for refractory or recurrent acute myeloid leukemia.
AB  - Between October 1991 and December 1998, 19 patients (12 males and 7 females) with
      refractory (six patients) or recurrent (13 patients) AML were treated with a
      combination chemotherapy of cytarabine given by continuous infusion over 24-h at
      a rate of 1 upward arrow g/m2 per day for 5 days along with idarubicin (12 upward
      arrow mg/m2 per day x 3) and etoposide (150 mg /m(2) per day x 3). Median age of
      the patients was 28 years (range, 15--61). Seven (37%) of 19 patients achieved
      complete remission (CR) with median CR duration of 6.7 months (range, 2.5-
      61.4+). Two patients are surviving for long term (50.1 and 62.6 months).
      Myelosuppression associated with chemotherapy was severe. Median recovery time to
      ANC over 500/microl was 28 days (range, 25--59). A significant proportion of
      patients experienced grade III-VI non-hematologic toxicities including
      nausea/vomiting (32%), liver function abnormality (32%), and diarrhea (16%). No
      central nervous system (CNS) toxicity was observed. Our study showed that the
      administration of cytarabine at a dose of 1 g/m(2) per day by continuous
      intravenous infusion for 5 days along with idarubicin and etoposide was feasible.
      Further studies are necessary to elucidate optimum dose and schedule of
      cytarabine in a setting of refractory or relapsed acute myeloid leukemia (AML).

PMID- 11226518
TI  - MUC1 expression in plasmacytoma.
AB  - Plasmacytoma (Pm) is a plasma cell (PC) neoplasia consisting of PCs and some of
      them show progression to multiple myeloma. But there is no clear indicators
      predicting this progression. In this study, MUC1 expression was evaluated in Pm
      cases to determine the predictive value and was compared with histopathologic
      grade which is known to be a prognostic indicator in Pm. Nine of 31 cases with Pm
      showed MUC1 expression. Only two of the 18 cases with mature morphology showed
      MUC1 expression while seven of 13 cases with immature morphology showed MUC1
      expression and this was statistically significant (P<0.006). Additionally, four
      of 11 cases with BM involvement showed MUC1 expression while five of 20 cases
      without BM involvement showed MUC1 expression. There was a trend MUC1 expression
      with BM involvement but there was not statistically significant association
      between MUC1 expression and BM involvement. We found that MUC1 expression is
      associated with immature morphology which is an important prognostic indicator in
      Pm and by analogy MUC1 expression may be an additional prognostic indicator in
      patients with Pm.

PMID- 11226519
TI  - Evidence of an immunologic mechanism behind the therapeutical effects of arsenic
      trioxide (As(2)O(3)) on myeloma cells.
AB  - Exposure of RPMI 8226, Karpas 707 and U266 human myeloma-like lines to low doses
      of As(2)O(3) was followed by a marked increase in lymphokine activated killers
      (LAK)-mediated killing and up- modulation of CD38 and CD54, two molecules
      involved in cell-cell interactions. Moreover, simultaneous exposure of effectors
      and targets to As(2)O(3) yielded the most effective condition for lysis. The
      expression of CD31 (CD38 ligand) and CD11a (CD54 ligand) was also up-regulated by
      LAK, suggesting that increased adhesion was responsible for the improved killing.
      Similar results were obtained using freshly isolated myeloma cells. These
      findings indicate that As(2)O(3) may be useful to boost the immune system against
      myelomas.

PMID- 11226520
TI  - Co-biomodulation with arsenic trioxide in multiple myeloma.

PMID- 11226521
TI  - Phorbol ester responsiveness of the glutathione S-transferase P1 gene promoter
      involves an inducible c-jun binding in human K562 leukemia cells.
AB  - Overexpression of the glutathione S-transferase P1 (GSTP1) gene is related to
      drug resistance in human cancer cells. However, the mechanisms of the
      transcriptional activation of this gene remain unclear. In this study, we
      examined the molecular mechanisms underlying phorbol ester mediated gene
      regulation using human K562 leukemia cells as a model. Promoter deletion analyses
      revealed that the activator protein-1 (AP-1) transcription factor site was
      crucial for 12-O-tetradecanoyl phorbol 13-acetate (TPA)-mediated GSTP1 gene
      transcription. Electrophoretic mobility shift assays and transient transfection
      analysis demonstrated that both DNA binding and transactivation activities of AP
      1 were induced by TPA. By supershift analysis, we identified transcription
      factors c-jun and fra-1 as well as NF-E2p45 as components of the induced binding
      complex. These results show for the first time that the phorbol ester TPA is
      involved in the molecular mechanism(s) mediating the activation of the GSTP1
      promoter in a human leukemia model.

PMID- 11226522
TI  - The efficient generation of CD83 positive immunocompetent dendritic cells from
      CD14 positive acute myelomonocytic or monocytic leukemia cells in vitro.
AB  - The ability of leukemic cells to differentiate to mature dendritic cells (DCs)
      was investigated in six acute myelomonocytic or monocytic leukemia cases. It was
      found that CD14 positive cells were more efficiently changed to CD83 positive
      mature typed DCs with granulocyte-macrophage colony-stimulating factor (GM
      CSF)/interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-alpha) compared
      with CD14 negative cells. Such leukemia derived DCs expressed a sufficient level
      of costimulatory molecules (CD80 and CD86), and were shown to be monoclonal based
      on an the X-inactivation analysis. They also stimulated not only allo- but auto-T
      lymphocytes, which thereafter became cytotoxic T lymphocytes (CTLs).

PMID- 11226523
TI  - Granular lymphocytic leukemia derived from gamma delta T-cell expressing
      cytotoxic molecules.
AB  - We here present an extremely rare case of granular lymphocytic leukemia derived
      from gamma delta T-cell (gamma delta T-GLL). The blood picture at diagnosis was
      as follows; white cell count 25.7 x 10(9)/l containing 94% atypical lymphocytes
      with cytoplasmic granules, hemoglobin 11.8 g/dl and platelet count 124 x 10(9)/l.
      The atypical lymphocytes were positive for CD2, CD3, CD5, CD7, CD56 and TCR gamma
      delta, but negative for CD4, CD8, CD57, TCR alpha beta and B-cell antigens. The
      cytotoxic molecules, T-cell intracellular antigen-1 (TIA-1) and granzyme B, were
      positive by immunocytochemical analysis. Southern blot analysis showed
      rearrangement of T-cell receptor J gamma and C beta genes but germline
      configuration of the JH gene. Neither serum antibody against human T-cell
      leukemia virus type-I (HTLV-I) nor the integration of HTLV-I proviral DNA was
      detected. CT scan showed splenomegaly but no lymph node enlargement. A diagnosis
      of gamma delta T-GLL was made, and she has been followed up without any therapies
      for more than 4 years.

PMID- 11226524
TI  - Talc induced transfusion independence in a patient with myelodysplasia.
AB  - Myelodysplasia with refractory anemia is associated with transfusion dependence.

PMID- 11226525
TI  - High-dose chemotherapy and APSCT as a potential cure for relapsing hemolysing
      AILD.
AB  - Angioimmunoblastic lymphadenopathy with dysproteinemia (or dysgammaglobulinemia)
      (AILD) is a lymphoproliferative disorder with cytogenetic and molecular
      abnormalities characteristic of malignant T-cell lymphoma (angioimmunoblastic T
      cell lymphoma -- AITL). We report the clinical course of a 58-year-old male
      patient with unusually aggressive AILD, including severe hemolysis and Guillain
      Barre syndrome, who entered complete remission after CHOP therapy, but had a full
      relapse after 2 months. At relapse, treatment with high-dose chemotherapy
      followed by autologous peripheral stem cell transplantation (APSCT) with CD34
      selected cells was shown to be successful. The patient is alive and disease-free
      3 years after diagnosis and 32 months after APSCT. Considering the poor prognosis
      of the majority of patients with AILD, intensive treatment followed by APSCT, may
      be a subject for further studies.

PMID- 11226526
TI  - Corrigendum to: Frequent microsatellite instability and BAX mutations in T cell
      acute lymphoblastic leukemia cell lines Leukemia Research 24 (2000), 255-262.

PMID- 11226527
TI  - The cow with zits.

PMID- 11226528
TI  - Comment.

PMID- 11226530
TI  - Intensive care unit outcomes.

PMID- 11226531
TI  - Parathyroid autotransplantation: an update.

PMID- 11226529
TI  - Imaging modalities for thoracic aortic injury: what's new?

PMID- 11226532
TI  - Laparoscopic inguinal hernia repair.

PMID- 11226533
TI  - Total parenteral nutrition and infections.

PMID- 11226534
TI  - Laryngeal nerve.

PMID- 11226535
TI  - Benefits of skin-sparing mastectomy: part 1 of the 6-part series on current
      concepts in breast reconstruction.

PMID- 11226536
TI  - Bronchoalveolar carcinoma.

PMID- 11226537
TI  - Update on the role of elective neck dissection for cancer of the aerodigestive
      tract.

PMID- 11226538
TI  - Mediastinoscopy in the staging of lung cancer.

PMID- 11226539
TI  - Surgical management of splenic disease.

PMID- 11226541
TI  - An examined and an enchanted life(2)(2).

PMID- 11226540
TI  - Laparoscopic splenectomy.

PMID- 11226542
TI  - Bioabsorption qualities of chitosan-absorbable vascular templates(1).
AB  - PURPOSE:The scope of endovascular surgical techniques has expanded to include the
      treatment of diseases considered at one time to be amenable only to surgical
      treatment. The development of the biodegradable template follows as an extension
      of current permanent stent technology. The goal of our project is to develop and
      test chitosan as an absorbable template for the vascular system.Ultrapure
      chitosan, heparin sodium salt and lysozyme, and contrast agents MD-76R and Oxilan
      350 were used to give radioopaque quality. Prototype chitosan vascular templates
      were obtained by a dip coating method in which alternate layers of chitosan were
      coagulated with nonsolvents or heparin. The amount of loaded and released heparin
      was determined using Azure II colorimetric assay. In vitro enzymatic degradation
      of templates was evaluated using lysozyme solutions in phosphate buffered saline.
      Mechanical properties were analyzed using the Dynamic Mechanical Analyzer, DMA-7
      (Perkin Elmer, Foster City, Calif.). The microstructure of freeze-dried templates
      was investigated by field emission scanning electron microscopy (FE SEM) using an
      LEO 982 electron microscope (Zeiss, Thornwood, NY).In vivo deployment of the
      templates was undertaken in 10 full-sized pigs (Sus scrofa). After open expose
      and control of the iliac artery, a closed balloon catheter technique was used to
      advance and place the balloon catheter and template. The balloon was then
      expanded, deploying a Palmaz stent with a chitosan template anchored distally.
      Patency and deployment of the stent-template complex was confirmed by an
      arteriogram. The animals were sacrificed at 1, 2, 3, 4, and 5 weeks poststent
      placement, and arterial sections were taken for microscopic analysis. The amount
      of chitosan remaining was estimated to determine an in vivo rate of absorption.On
      hematoxilyn and eosin staining of the section arterial samples, a marked
      inflammatory response was noted and progressed with duration of in vivo contact.
      A giant cell foreign body reaction coupled with intense intimal hyperplasia and
      organized thrombus was also noted and progressed with duration of time in vivo.
      Also noted was the degradation of the template material with only small remnants
      of material noted within the giant cell by week 4. Clinically, none of the pigs
      developed limb ischemia or evidence of thromboembolic events.In this in vivo
      study, the chitosan template proved to be biodegradable but elicited an intense
      thrombotic and foreign body reaction despite heparin bonding. Further
      investigation is ongoing as to decreasing the thrombogenic and antigenic
      qualities of the template materials by either alteration of the base material or
      addition of bioactive side chains.

PMID- 11226543
TI  - 5-year qualitative results of isolated cryosurgical ablation for hepatic
      malignancy at Walter Reed Army Medical Center(1).
AB  - Cryosurgical ablation (CSA) is an established treatment for primary and
      metastatic liver malignancies. The study objective was to qualitatively define
      our patient CSA experience and compare it with the existing literature.A
      retrospective review was conducted of patients who underwent isolated CSA from
      September 1995 to April 2000. Data were collected on patient characteristics,
      tumor characteristics, sequential 12-hour laboratory data, transfusion
      requirements, and survival data. SPSS 9.0 (SPSS, Chicago, Illinois) was used for
      data analysis.Twenty-four patients (14 men, 10 women) were studied. Eighty-seven
      lesions (mean 3.8/patient) were treated. Six patients underwent treatment for
      primary liver tumors, whereas 16 were treated for metastatic disease. White blood
      cell count increased 1.7-fold, and platelet count decreased 2.0-fold. Aspartate
      aminotransferase and alanine aminotransferase increased significantly 42- and 29
      fold, respectively. Seven out of 21 (33%) patients required blood transfusion.
      Our overall complication rate was 25%. Perioperative mortality was 0%. Kaplan
      Meier survival analysis revealed an overall survival of 46% at a median follow-up
      of 33.7 +/- 6.8 months.CONCLUSIONS:Although isolated CSA of hepatic malignancies
      results in major and minor alterations in serologic parameters, they equate to
      little clinical significance. Blood product transfusions are necessary in 30%
      patients post-CSA. Significant perioperative complications occur in 25% of
      patients. Survival estimates suggest that nearly 50% of patients undergoing CSA
      can be expected to survive longer than 2 years post-CSA.

PMID- 11226544
TI  - Gastrin-releasing peptide: a potential growth factor expressed in human
      neuroblastoma tumors(1).
AB  - PURPOSE:Gastrin-releasing peptide (GRP) is a 27-amino acid neuropeptide that has
      been identified in the cytoplasm of many neuroendocrine tumors. Gastrin releasing
      peptide has been labeled as an autocrine growth factor in small cell lung
      carcinomas. Recent work has also shown this to be true in the growth of
      neuroblastoma cells in vitro. The purpose of this study was to demonstrate GRP
      and its receptor (GRP-R) in resected human neuroblastomas and to correlate the
      presence or absence with other known predictors of poor prognosis.To demonstrate
      the presence of GRP and GRP-R mRNA, total RNA was extracted from human
      neuroblastoma cells. A reverse transcription-polymerase chain reaction (RT-PCR)
      was then performed using specific primers. The products of the RT-PCR were then
      confirmed to be GRP and GRP-R cDNA by Southern blot analysis. The RT-PCR products
      were then sequenced, and these sequences were compared with the know sequences of
      GRP and GRP-R DNA.N = 19. GRP and GRP-R mRNA were present in all neuroblastoma
      specimens. Although no correlation with other known predictors of poor prognosis
      existed, transcripts of four different sizes (400, 450, 500, and 950 bp) were
      seen in the GRP-R transcripts. The sequences of the 950 bp-sized transcript
      reverse transcription PCR products were identical to the known GRP-R.We conclude
      that gastrin releasing peptide and gastrin releasing peptide receptor mRNA are
      present in all human neuroblastomas. Although qualitatively it appears to lack
      prognostic significance, its ubiquitous nature in the tumor suggests it may be a
      useful target on which to base future treatment modalities.

PMID- 11226545
TI  - Trauma experience comparison of army forward surgical team surgeons at Ben Taub
      Hospital and Madigan Army Medical Center(2)(2).
AB  - Far forward life-saving surgical care is the mission of an army forward surgical
      team (FST). Trauma skill maintenance is necessary to complete that mission. A new
      program has been developed for FST training using the resources of a Level 1
      trauma center. We sought to compare the experience of FST surgeons at a major
      urban trauma center with the yearly trauma experience at an army Level 2 trauma
      center.General surgeons of the 250th FST prospectively tabulated data for trauma
      patients during a September 1999 unit deployment to Ben Taub Hospital (Houston,
      Texas). Data collected included nature and location of injury, hospital
      admission, and surgical intervention. During 1999, similar data were collected at
      Madigan Army Medical Center (MAMC) (Ft. Lewis, Washington), home station of the
      250th and Level 2 trauma center since November 1998.The FST general surgeons
      observed 319 injuries. Of those injured, 104 were admitted and 19 underwent
      urgent operation. Direct participation by FST general surgeons in the operative
      procedures varied. In 1999, MAMC general surgeons treated 455 trauma victims in
      direct supervision of Army general surgery residents. Madigan Army Medical Center
      general surgeons admitted 304 and urgently operated on 57 trauma patients, while
      107 patients were transferred to another institution for definitive management of
      orthopedic and nonoperative neurosurgical injuries.CONCLUSIONS:The volume of
      trauma surgical cases at MAMC during 1999 was 3 times that seen in the 1-month
      rotation at Ben Taub. General surgeons performed more trauma and abdominal
      surgery at MAMC with significantly more direct involvement in patient care and
      operative procedures. The experience of the 250th FST does not justify trauma
      sustainment deployments for surgeons from military trauma centers.

PMID- 11226546
TI  - Cervical spine instability: clearance using dynamic fluoroscopy.
AB  - Cle aring the cervical spine in a multiply injured trauma patient is a dilemma
      because clinical examination for ligamentous instability cannot be performed, and
      the standard cervical spine series can miss isolated ligamentous injury. Static
      flexion/extension views are unsafe, as the obtunded patient has no protective
      reflexes and cannot complain of pain during the exam. This results in a need for
      prolonged spinal immobilization and its attendant complications. Dynamic
      fluoroscopy may be useful in the detection of otherwise occult injuries.We
      performed a prospective study of a cervical spine clearance algorithm
      incorporating dynamic fluoroscopy with flexion/extension views. Inpatient records
      over a 3-year period were reviewed. Patient demographic data, results of cervical
      spine films and fluoroscopic exams, interventions based on positive results, and
      missed injuries were recorded.One hundred ten patients with normal spine plain
      films underwent dynamic fluoroscopy with flexion and extension views of the
      cervical spine. The average Glasgow Coma Score was 9.2 and the average revised
      Trauma Score was 9.5. Nine patients had evidence of cervical instability on exam.
      Six of these were deemed stable by the orthopedic or neurosurgical spine
      consultants, and these patients had their hard collars removed. One patient with
      positive findings had cervical immobilization with hard collar continued, a
      second had halo placement, and a third underwent spinal fusion for atlanto
      occipital disassociation. No patients undergoing dynamic fluoroscopy were
      subsequently found to have missed cervical spine injury.With our protocol, 3
      patients had significant cervical instability that would have been missed without
      dynamic fluoroscopy. Given the significant medical and legal ramifications of
      missed cervical spine injury and the benefits of early removal of cervical
      collars, more widespread use of dynamic fluoroscopy of the cervical spine is
      warranted.

PMID- 11226547
TI  - Commentary.

PMID- 11226548
TI  - The role of the journal club in surgical residency programs: a survey of APDS
      program directors.
AB  - PURPOSE:To determine the role, organization, and importance of journal clubs in
      surgical education.Program directors of all general surgical residencies were
      asked to respond by mail to a structured survey containing questions about their
      journal club in the following general categories: Setting, Format, Content, and
      Purpose.With over 80% of the 278 program directors responding, the typical
      journal club was found to be one that meets once per month to discuss 3 to 6
      articles. It is held on site in the early evening hours and requires the
      attendance of residents. Over half of the directors indicated that their journal
      club was important or very important to their training program, with learning
      literature review skills and providing training in research education as the top
      2 purposes cited. Few programs reported performing any systematic or formal
      evaluation of their journal club.Although journal clubs are active in over 65% of
      general surgery residency programs, little data exist on the purposes served by
      this aspect of resident training. The data provided by program directors in
      response to this survey will ideally serve as a starting point for discussion of
      how to maximize the benefits that residents receive from this part of their
      curriculum. Adoption of more formalized approaches to evaluating outcomes would
      assist in this process.

PMID- 11226549
TI  - In memoriam: George L. Engel, M.D.

PMID- 11226550
TI  - Changes in psychiatric diagnoses from admission to discharge: review of the
      charts of 159 patients consecutively admitted to a geriatric psychiatry inpatient
      unit.
AB  - The diagnosis of psychopathology among geriatric acute inpatients requires
      comprehensive evaluation. To our knowledge, no recently published papers in the
      geriatric psychiatry literature have systematically examined diagnostic changes
      during single admissions. We reviewed the charts of 159 patients consecutively
      admitted to an acute geriatric psychiatry unit over 18 months. We recorded
      admission diagnoses from initial treatment plans, and discharge diagnoses from
      discharge summaries. Mean patient age was 80 years and average length of stay was
      17 days. The most common primary diagnoses were psychotic and depressive
      disorders. The most common secondary diagnoses were dementias and depressive
      disorders. Primary diagnoses changed from admission to discharge in 31 patients
      (20%), and secondary diagnoses changed in 76 patients (48%). There was a
      significant change involving the diagnosis of dementia, but not that of
      depressive or psychotic disorders. A large proportion of inpatients had their
      diagnoses altered, especially those involving dementias, during hospitalization.
      Inpatient admission may be valuable for clarifying the diagnoses of elderly
      psychiatric patients.

PMID- 11226551
TI  - Does psychiatric comorbidity increase the length of stay in general hospitals?
AB  - Several studies reported that in non-psychiatric hospital departments mentally
      ill patients have a longer length of hospital stay than mentally well. But their
      methods are often limited because other predictors of length of stay were
      excluded from statistical analyses. Using the Clinical Interview Schedule,
      research psychiatrists interviewed 993 patients of medical, surgical,
      gynecological, and rehabilitation departments in Austria. Using several multiple
      regression analyses, the influence of psychiatric comorbidity and other variables
      on length of stay was analyzed. 32.2% of all patients suffered from psychiatric
      morbidity. Of all psychiatric cases, 6.2% received more than one psychiatric
      diagnosis. Presence of psychiatric disorders, age, a diagnosis of neoplasms,
      number of all somatic diagnoses, and the number of previous non-psychiatric
      hospital admissions predicted length of stay. Patients with dementia, with
      substance abuse disorders, and with alcohol- and drug-related psychiatric
      disorders showed a significantly increased length of stay, while other
      psychiatric diagnoses did not differ from the mentally well. Even after
      controlling for confounding variables, dementia and substance related diagnoses
      increase the length of hospital stay. It is important to investigate
      interventions for early recognition and treatment of these disorders.

PMID- 11226552
TI  - Role of serotonin and noradrenaline in social dysfunction: a review of data on
      reboxetine and the Social Adaptation Self-evaluation Scale (SASS).
AB  - Social impairment is a common feature of depressive illness, often causing
      substantial and clinically meaningful dysfunction. Although the depressive
      symptoms and social impairment are linked, the naturalistic course and response
      to treatment of these two aspects of depression do not necessarily correlate. A
      variety of self-report and clinician-administered assessment scales which are
      specific for the measurement of social functioning and have good psychometric
      properties have been developed in the past 40 years. The most recent of these
      instruments is the Social Adaptation Self-evaluation Scale (SASS), a 21-item
      scale designed in 1989 to assess patient response to antidepressant treatment.
      SASS was used in two clinical trials comparing reboxetine, the new selective
      noradrenaline reuptake inhibitor (selective NRI), with fluoxetine. While no
      difference in efficacy was detectable by traditional assessments of symptoms,
      reboxetine proved to be significantly more effective than fluoxetine in improving
      social functioning in patients with depression. Reboxetine was also more
      effective than fluoxetine in rectifying social functioning in the subset of
      patients who remitted from an episode of major depression. Specifically,
      reboxetine improved patient motivation, energy and self-perception. These results
      indicate that antidepressant therapy can achieve more than symptom relief in
      depression. It is speculated that there may be a difference in the roles played
      by serotonin and noradrenaline in social functioning.

PMID- 11226553
TI  - Evaluation of the Confusion Assessment Method (CAM) as a screening tool for
      delirium in the emergency room.
AB  - The objective of this study was to compare the results of the Confusion
      Assessment Method (CAM) obtained by a trained non-physician interviewer to those
      obtained by a geriatrician, among a sample of elderly patients seen in an
      emergency room. A group of 110 elderly patients (> or =66 years) were evaluated
      in the emergency room by a lay interviewer. The geriatrician conducted an
      interview in the presence of the lay interviewer. Subsequently, the geriatrician
      and the lay interviewer completed a CAM checklist independently. Kappa
      statistics, sensitivity, specificity, positivity predictive value (PPV), and
      negative predictive value (NPV) for the geriatrician's and lay interviewer's
      results with the CAM diagnostic algorithm were compared. The kappa coefficient
      was 0.91, the sensitivity 0.86, the specificity 1.00, the PPV 1.00, and the NPV
      0.97. In conclusion, the CAM used by a trained lay interviewer in the emergency
      room is sensitive, specific, reliable and easy to use for the identification of
      patients with delirium. The under-recognition and under-treatment of delirium is
      a major health issue and has important clinical and financial implications. The
      implementation of systematic screening in populations at risk could increase the
      rate of early detection and lead to the appropriate management of delirious
      patients.

PMID- 11226554
TI  - Is the substance abuse of inpatients with schizophrenia overlooked?
AB  - The utility of medical records and clinician reports for assessing substance
      abuse among inpatients with schizophrenia or schizoaffective disorder was
      assessed in a sample of 296 patients recruited from four general hospitals in New
      York City. Measures derived from the medical record, the discharge summary, and
      primary clinician reports are compared to the results of a structured diagnostic
      interview. Analysis of the sensitivity, specificity, positive predictive value,
      and overall accuracy of the nondiagnostic sources found unexpectedly high levels
      of detection. Discharge summaries had the lowest sensitivity when compared to the
      diagnostic interview, raising concern that inpatient staff and clinicians may
      fail to communicate substance abuse problems to outpatient providers.

PMID- 11226555
TI  - Meperidine addiction or treatment frustration?
AB  - There have been few studies of the psychiatric characteristics of analgesics
      addiction. The physician's perceptions that patients were addicted to analgesics
      might be partially attributable to frustration with poor response to treatment.
      In this retrospective study, we evaluated the medical records of 20 subjects (15
      male and 5 female) who were perceived as having addiction to meperidine by
      general physicians. The most common medical diagnosis among these patients was
      chronic pancreatitis (7/20). Among them, five had a past history of suicide
      attempt and three had self-injury behavior during the index admission. The fact
      that subjects were perceived as being addicted might be attributable to a vicious
      cycle of the following factors: 1) chronic intractable pain; 2) poor staff
      patient relationship; 3) lower pain threshold or tolerance due to anxiety or
      depression; 4) patients with a history or tendency of substance abuse; 5) placebo
      use and inadequate analgesics regimen. The findings of this study suggest that
      the importance of the following diagnostic and treatment procedures in these
      patients: 1) suicide risk should be evaluated; 2) comorbid psychiatric diseases
      should be treated; 3) factors that cause a vicious cycle in pain control should
      be identified; 4) misconceptions of opiate analgesics among medical staff should
      be discussed; 5) poor staff-patient relationship should be managed aggressively;
      and 6) "addiction" is a critical diagnosis that should be avoided if possible.

PMID- 11226556
TI  - Clinical utility and validation of the Japanese version of Memorial Delirium
      Assessment Scale in a psychogeriatric inpatient setting.
AB  - Delirium is a common mental disorder in the elderly. The Memorial Delirium
      Assessment Scale (MDAS) was developed in 1997 to assess delirium severity over
      time. The purpose of the current prospective study is to assess the clinical
      utility, diagnostic potential, reliability and validity of the Japanese version
      of MDAS in a psychogeriatric unit setting. Reliability was examined by testing 37
      elderly patients; validity was examined concurrently by 16 patients with
      delirium. Two psychiatrists evaluated each patient simultaneously. Mean MDAS
      ratings differed among groups of patients with delirium, dementia, or no
      cognitive impairment. High levels of consistency within raters (Cronbach's
      alpha=0.92) and reliability between raters (0.98) were indicated. The correlation
      between MDAS scores and rating on the Delirium Rating Scale (r=.74, P=.0011), the
      Clinician's Global Rating of delirium severity (r=.67, P=.0047), and the Mini
      Mental State Examination (r=-.54, P=.029) was fair. The MDAS seems to be a
      reliable measuring instrument for assessing delirium in elderly patients.

PMID- 11226557
TI  - Optimized protocols for the detection of porcine circovirus 2 DNA from formalin
      fixed paraffin-embedded tissues using nested polymerase chain reaction and
      comparison of nested PCR with in situ hybridization.
AB  - Optimized DNA extraction method and nested polymerase chain reaction (PCR) were
      developed for the detection of porcine circovirus 2 (PCV2) from formalin-fixed,
      paraffin-embedded tissues. Conventional PCR, nested PCR, and in situ
      hybridization methods were also compared for the detection of PCV2 in archival
      tissues. A method based on xylene deparaffinization followed by proteinase K
      digestion yielded DNA of sufficient quality for PCR analyses reliably and
      consistently. Twenty-six (70%) of the 37 tissues examined gave positive results
      with conventional PCR, whereas all the 37 tissues gave positive results using the
      nested PCR. A distinct positive signal for PCV2 was detected in spleen and lymph
      node from all the 37 pigs by in situ hybridization. The nested PCR and in situ
      hybridization could be applied successfully to archival tissues for the detection
      of porcine circovirus 2 DNA.

PMID- 11226558
TI  - Rapid and sensitive diagnosis of human adenovirus infections by a generic
      polymerase chain reaction.
AB  - A new adenovirus specific nested polymerase chain reaction (PCR) method is
      described. It was designed inside the hexon protein gene of the adenovirus
      genome, and was able to detect DNA of all 47 human adenovirus types in a wide
      range of clinical samples. A sensitive internal control system able to assure
      proper analytical conditions for the amplification of as few as 100 molecules of
      a heterologous DNA was included to avoid false negative results. Sensitivity was
      estimated at about 10 molecules per tube of a plasmid containing an insert of the
      first amplification product. The method was able to detect adenovirus infection
      in 31/43 conjunctival scrapings from patients with acute kerato conjunctivitis
      10/40 nasopharyngeal aspirates from patients admitted to hospital with acute
      respiratory disease and 2/26 urine samples from patients with haemorrhagic
      cystitis with better sensitivity than cell culture or rapid diagnosis by antigen
      detection by immunofluorescence (IF) in the case of respiratory specimens. Only
      two of 17 stools positive for a group F adenovirus specific latex immunoassay
      were PCR negative. The internal control system avoided a false negative result on
      another two stool samples. In conclusion, the method described below was shown to
      be useful for rapid diagnosis of adenovirus infections with higher sensitivity
      than antigen detection by IF.

PMID- 11226559
TI  - A simple procedure for expression and purification of selected non-structural
      (alpha and beta) herpes simplex virus 1 (HSV-1) proteins.
AB  - The expression and isolation of herpes simplex virus 1 (HSV-1) immediate early
      (alpha) IE63 (ICP27) and of the early (beta) thymidine kinase (Tk) polypeptides
      in Escherichia coli JM 109 cells transformed with the PinPoint Xa-1 (Promega)
      plasmid construct carrying either the HSV-1 UL54 or UL23 genes are described. The
      resulting biotinylated fusion protein(s) could be easily induced and were
      purified in appropriate amounts by means of a monomeric avidin-conjugated resin
      (SoftLink Soft Release Avidin Resin, Promega) provided that: (1) the exponential
      growth of the selected transformed cells was monitored carefully; (2) the post
      induction harvest interval was properly chosen; and (3) the period for adsorption
      to the avidin resin suitably adjusted. The isolated protein(s), although
      partially digested in the case of the IE63 polypeptide, were suitable antigen(s)
      for immunization of various animal species. Co-purification of trace amounts of
      endogenous biotinylated protein(s) produced in E. coli was eliminated by
      shortening the duration of adsorption to the avidin resin.

PMID- 11226560
TI  - Optimisation and sensitivity of single-stranded conformation polymorphism for the
      detection of hepatitis C virus quasi-species.
AB  - Single-stranded conformation polymorphism (SSCP) is a technique used widely for
      the detection of differences in DNA sequence based on PCR technology. Developed
      by geneticists for the detection of mutations causing disease, it has been
      adopted more recently for the analysis of the quasi-species of viral genomes,
      such as hepatitis C virus (HCV). The rigorous standardisation and determination
      of the limit of detection of the technique has rarely been shown. Variants within
      the quasi-species of the hypervariable region of HCV were cloned into pUC119 and
      the resulting plasmids quantitated and used as templates to optimise SSCP.
      Variables studied included the number of variants detected, the sensitivity of
      detection of variants in the minority, the electrophoresis temperature, methods
      of generation of single-stranded DNA, effect of numbers of cycles of PCR and use
      of DNA polymerase with proof-reading ability. It was demonstrated that the
      optimised method could detect at least five variants within a quasi-species and
      that variants could be detected down to a level of 2% of the quasi-species.
      Electrophoresis at room temperature for 18 h was highly reproducible. Generation
      of single-stranded DNA using a single primer with Taq polymerase for 20 cycles
      gave an accurate reflection of the quasi-species make-up and use of Pfu
      polymerase reduced sensitivity of detection of minor bands. This SSCP method
      provides an accurate tool to evaluate HCV quasi-species.

PMID- 11226561
TI  - An international collaborative study to establish the 1st international standard
      for HIV-1 RNA for use in nucleic acid-based techniques.
AB  - Twenty-six laboratories from 10 different countries participated in a
      collaborative study to establish the 1st International Standard for HIV-1 RNA for
      use in nucleic acid-based techniques (NAT). Three candidate preparations were
      tested all based on genotype B viruses. The candidates were tested by each
      laboratory at a range of dilutions in four independent assays and the results
      collated and analysed statistically. All three candidates gave results that were
      tightly grouped, with little difference between the results from different
      laboratories or from the use of different assays. Studies of relative potency
      showed good agreement between laboratories. There were no significant differences
      between five commercial assay types, except that candidate XX showed a slightly
      lower potency compared to YY and ZZ with a single commercial assay. The reason
      for this was not established. Degradation studies showed that the freeze-dried
      preparations were stable at -20,4 and 20 degrees C for 26 weeks, the longest
      period studied, but that they became difficult to reconstitute after 3 weeks at
      45 degrees C and 9 weeks at 37 degrees C. As a result of the study, the World
      Health Organisation (WHO) Expert Committee on Biological Standardisation (ECBS)
      established the preparation referred to as candidate YY (NIBSC Code No. 97/656)
      as the 1st International Standard for HIV-1 RNA for use with NAT with an assigned
      potency of 100000 International Units per vial.

PMID- 11226562
TI  - Differentiation of cassava-infecting begomoviruses using heteroduplex mobility
      assays.
AB  - Cassava mosaic disease is an enormous problem affecting the viability and
      productivity of cassava in all the developing regions in Africa. The disease is
      now known to be caused by a number of cassava-infecting begomoviruses. New
      viruses and viral strains continue to be discovered and due to the lack of
      cloning and sequencing facilities in many African laboratories, a simple, rapid
      and sensitive technique is needed for screening of cassava plantations. Here we
      report on the development of a heteroduplex mobility assay (HMA) which could be
      used for the testing of viral-infected cassava. The assay involves amplifying the
      highly conserved core region of the coat protein gene of field isolates followed
      by denaturing and annealing with a number of reference strains. The HMA profiles
      in this study were able to differentiate four different viral species and 11
      different virus strains, and showed a good correlation with sequencing results
      and phylogenetic comparisons with other sequenced cassava viruses. This technique
      is sensitive and rapid and has the added advantage of being able to detect
      mixtures of viruses in field-grown cassava.

PMID- 11226563
TI  - Integrated RT-PCR/nested PCR diagnosis for differentiating between subgroups of
      plum pox virus.
AB  - An RT-PCR/nested PCR technique was developed for the simultaneous detection and
      typing of plum pox virus (PPV) and its major types--Dideron (D), Marcus (M), El
      Amar (EA) and Cherry (C). Degenerated oligonucleotides were synthesized for the
      general detection of PPV, flanking the coding sequence for the N-terminal portion
      of the coat protein (CP), within which strain-specific differences were
      identified. On the basis of these characteristic differences, degenerated primer
      pairs were designed to differentiate between the four major subgroups of the
      virus in nested PCR reactions. The validity of the technique was tested on viral
      strains and cloned cDNAs overlapping the CP region. High specificity was observed
      with no detectable cross-reactions. The results of general PPV detection with the
      new primers and those of the PCR-based detection of the 3' non-coding region of
      the viral genome correlated with complete coincidence. The PCR typing results
      correlated well with those of the RsaI-RFLP and serological typing and revealed a
      surprisingly high incidence of PPV-D in Hungary.

PMID- 11226564
TI  - Translational extracts active biologically in vitro obtained from eukaryotic
      monolayer cells: a versatile method for viral RNA studies.
AB  - Preservation of enzymatic activities in biological samples, especially after
      freeze/thawing, is a crucial requirement in virological research. Theoretically,
      this preservation can be achieved with the presence of cryopreservative agents.
      In contrast to tedious methods, it was found that this might be readily achieved
      by using well-defined conditions, including sucrose in the samples. Hence, the
      generation of a translational extract obtained from eukaryotic cells that have
      grown as monolayers is described below. This versatile method could be used
      advantageously for the in vitro translation of messenger RNAs, added exogenously,
      including viral mRNAs. The translational extract can be prepared freshly on a
      daily basis, or more conveniently it can be frozen and thawed subsequently for
      further use, without loss of activity. It can replace the Krebs ascites fluid and
      the commercial rabbit reticulocyte lysate. The procedure employed for the
      preservation of the biological activity of the translational extract can be
      extended to various other biological samples.

PMID- 11226565
TI  - A quantitative, internally controlled real-time PCR Assay for the detection of
      parvovirus B19 DNA.
AB  - Parvovirus B19 is an erythrovirus causing diverse clinical manifestations ranging
      from asymptomatic or mild, to more severe outcomes in, for example, immune
      compromised patients. B19 is spread primarily via the respiratory route, but it
      can also be transmitted via blood and blood products. Viral loads in blood or
      plasma donations amount up to 10(11) genome equivalents/ml. Therefore, screening
      of plasma for fractionation for the presence of B19 and removal of highly loaded
      donations is a way to limit considerably the input of B19 into production pools
      and to improve further the safety of plasma products. An assay for the
      quantitative detection of B19 DNA, based on real-time PCR using ABI Prism SDS7700
      (TaqMan) is described here. This assay allows precise quantitation of viral loads
      over 7 orders of magnitude. An exogenous internal control (internal quality
      marker) is included in each individual sample to prevent false negative results.
      A linearized plasmid is used as an internal quality marker that contains the
      identical sequence of the B19 target sequence but with an altered probe
      hybridization site. This allows co-amplification of B19 and internal quality
      marker and co-detection of FAM (6-carboxyfluorescein) or VIC labeled probes
      respectively. The assay is validated according to current guidelines (of the
      International Conference on Harmonization, Paul Ehrlich Institute, and the
      Council of Europe) and is optimized for high throughput screening.

PMID- 11226566
TI  - Detection of prawn white spot bacilliform virus by immunoassay with recombinant
      antigen.
AB  - Prawn white spot bacilliform virus (WSBV) is the major pathogen of prawn disease.
      To develop a sensitive assay for the early detection of this virus, we generated
      an antibody against a WSBV-specific protein, P204. The p204 gene was cloned from
      a WSBV cDNA library and expressed in Escherichia coli. The peptide (P204) encoded
      by p204 was purified, and its antibody raised in mice. IgG fraction of the anti
      P204 serum was purified using a Sepharose column and the Fab fragment was
      obtained by pepsin digestion. An enzyme-linked immunosorbent assay (ELISA) using
      this Fab fragment was developed to detect the WSBV in prawn tissues. The
      experiments showed that Fab of anti-P204 antibody is highly specific for WSBV,
      and displays a sensitivity of 10(5) viral particles/mg prawn tissues. This is the
      first report using the Fab fragment prepared from a recombinant antigen to detect
      prawn viruses by ELISA.

PMID- 11226567
TI  - Type-independent detection of foot-and-mouth disease virus by monoclonal
      antibodies that bind to amino-terminal residues of capsid protein VP2.
AB  - The characterization of monoclonal antibodies raised against the foot-and-mouth
      disease virus isolates A22 Iraq/1964, Asia1 Shamir-Israel/1989, and SAT1
      Zimbabwe/1989 with regard to neutralizing activity and sensitivity of their
      epitopes for treatment with trypsin, resulted in the identification of one non
      neutralizing antibody in each panel that binds to a trypsin-sensitive epitope.
      Furthermore, each of these antibodies recognized 27 isolates of different
      provenance, representative of six serotypes. These antibodies are recommended for
      type-independent antigen detection by ELISA. The epitopes for these antibodies
      reside at the intertypically conserved N-terminus of capsid protein VP2. The two
      are specified by the lysines at positions two and three, but differ from each
      other as indicated by the variable heavy chain sequences of their antibodies.

PMID- 11226568
TI  - Human Jurkat lymphocytes clones differ in their capacity to support productive
      human immunodeficiency virus type 1 multiplication.
AB  - CD4-positive human lymphocytic cell lines are essential tools for the study of
      human immunodeficiency virus (HIV) replication. Jurkat cells are among cells more
      frequently used for this purpose. In the current study, various cell clones or
      cells stocks derived from this cell line were shown to vary substantially in
      their response to viral infection and in their ability to support productive
      virus multiplication. The formation of syncytia, the effect of Vpu on viral
      export, and especially the specific infectivity of the viruses released, can vary
      significantly among independent cell stocks. This suggests that the choice of an
      adequate cell clone or cell line could be critical while evaluating specific
      properties of the virus and further stresses the limitations of tissue culture
      models. However, these observations also raise the possibility of exploiting
      these differences among cells to study specific aspects of host-cell interactions
      contributing to viral multiplication.

PMID- 11226569
TI  - Genetic characterization of Puumala hantavirus strains from Belgium: evidence for
      a distinct phylogenetic lineage.
AB  - Puumala hantavirus (PUUV) sequences were recovered from red bank voles
      (Clethrionomys glareolus) trapped between 1996 and 1998 in four localities of
      southern Belgium: Thuin, Montbliart, Momignies and Couvin. In addition, three
      PUUV isolates originating from bank voles trapped in the 1980s in southern
      (Montbliart) and northern (Turnhout) Belgium were genetically characterized.
      Analysis of the complete S and partial M segment sequences showed that the
      Belgian PUUV strains constitute a genetic lineage, distinct from other known PUUV
      lineages from Europe and Japan. This lineage also includes a wild strain (Cg
      Erft) originating from a neighbouring area of Germany. Within the Belgian
      lineage, geographical clustering of genetic variants was observed. In the
      Montbliart site, the range of diversity between the most temporally distant
      strains (from 1986 and 1996-1998) was higher than between those from 1996 and
      1998, suggesting slight genetic drift via accumulation of neutral or quasi
      neutral substitutions with time.

PMID- 11226570
TI  - Nucleotide sequence variation of the VP7 gene of two G3-type rotaviruses isolated
      from dogs.
AB  - The sequence of the VP7 gene of two rotaviruses isolated from dogs in southern
      Italy was determined and the inferred amino acid sequence was compared with that
      of other rotavirus strains. There was very high nucleotide and amino acid
      identity between canine strain RV198/95 and other canine strains, and to the
      human strain HCR3A. Strain RV52/96, however, was found to have about 95% identity
      to the G3 serotype canine strains K9, A79-10 and CU-1 and 96% identity to strain
      RV198/95 and to the simian strain RRV. Therefore both of the canine strains
      belong to the G3 serotype. Nevertheless, detailed analysis of the VP7 variable
      regions revealed that RV52/96 possesses amino acid substitutions uncommon to the
      other canine isolates. In addition, strain RV52/96 exhibited a nucleotide
      divergence greater than 16% from all the other canine strains studied; however,
      it revealed the closest identity (90.4%) to the simian strain RRV. With only a
      few exceptions, phylogenetic analysis allowed clear differentiation of the G3
      rotaviruses on the basis of the species of origin. The nucleotide and amino acid
      variations observed in strain RV52/96 could account for the existence of a canine
      rotavirus G3 sub-type.

PMID- 11226571
TI  - Structural organization and analysis of the viral terminase gene locus of Tupaia
      herpesvirus.
AB  - Tupaia herpesvirus (THV) was isolated from spontaneously degenerating tissue
      cultures of malignant lymphoma, lung, and spleen cell cultures of tree shrews
      (Tupaia spp.). In order to determine the phylogenetic relatedness of THV the
      complete nucleotide sequence of the viral terminase (VTER) gene locus (6223 bp)
      of Tupaia herpesvirus strain 2 (THV-2) was elucidated and analysed. The VTER gene
      locus, encoding one of the most highly conserved herpes viral proteins is
      composed of two exons. The intron contains five potential open reading frames
      (ORFs). The arrangement of these ORFs is colinear with the corresponding regions
      in the genomes of the mammalian cytomegaloviruses. The precise primary structure
      of the THV-2 VTER splice junction was determined using RT-PCR and was found to be
      in agreement with the corresponding splice donor and acceptor sites of the
      mammalian cytomegaloviruses. The comparison of all six putative THV-2 proteins
      with the corresponding counterparts in other herpesviruses revealed that THV
      resides between the Human and the Murine cytomegalovirus (HCMV, MCMV). These
      results are in agreement with our previous statement, that THV and the known
      cytomegaloviruses are closely related to each other and should be classified into
      one taxonomic group. The genetic data presented here and in previous studies are
      based on the detailed comparison of highly conserved viral genes. Consequently,
      the classification of the Human and the cytomegaloviruses into the two genera
      Cyto- and Muromegalovirus, that is mainly based on overall genome structure,
      should be reconsidered.

PMID- 11226572
TI  - Contributions of gD receptors and glycosaminoglycan sulfation to cell fusion
      mediated by herpes simplex virus 1.
AB  - Two cell surface proteins (nectin-1/HveC and nectin-2/HveB) shown previously to
      serve as receptors for the entry of herpes simplex virus 1 (HSV-1) wild-type
      and/or mutant strains were found to serve also as receptors for HSV-1-induced
      cell fusion. Transfection with genomic DNA from a syncytial HSV-1 strain encoding
      wild-type gD resulted in fusion of Chinese hamster ovary (CHO) cells expressing
      nectin-1 but not of cells expressing nectin-2. In contrast, transfection with DNA
      from a related HSV-1 strain encoding the mutant Rid1 form of gD resulted in
      fusion of CHO cells expressing either receptor but not of control cells. These
      results are consistent with the ability of each receptor to mediate entry of
      viruses expressing wild-type or Rid1 gD and with results obtained previously with
      HVEM (HveA), a third HSV-l entry receptor. Undersulfation of GAGs in receptor
      expressing cell lines predictably reduced susceptibility to HSV-l infection. In
      contrast, susceptibility to cell fusion mediated by HVEM or nectin-1 was not
      reduced. Undersulfation of GAGs partially inhibited cell fusion mediated by
      nectin-2. We conclude that HSV-1-induced cell fusion requires a gD-binding entry
      receptor, that ability of an HSV-1 strain to use HVEM, nectin-2 or nectin-1 for
      cell fusion depends on the allele of gD expressed and that GAGs may influence
      cell fusion, dependent on the gD-binding receptor used, but are less important
      for cell fusion mediated by HVEM, nectin-2 or nectin-l than for viral entry.

PMID- 11226573
TI  - An ORF-2a protein is not present at a significant level in virions of the
      arterivirus lactate dehydrogenase-elevating virus.
AB  - MRNA2 of the arteriviruses lactate dehydrogenase-elevating virus (LDV) and equine
      arteritis virus (EAV) encodes two proteins that are read in different frames, an
      about 26 kDa minor envelope glycoprotein and an about 8 kDa protein that lacks N
      glycosylation sites and a signal peptide, but possesses a central hydrophobic
      segment. Recent studies have shown that both proteins of EAV are translated from
      mRNA 2 in EAV infected BHK cells, that the 8 kDa protein is membrane associated
      and that small amounts of it are recovered in purified virions (Snijder, E.J.,
      van Tol, H., Pederson, K.W., Raamsman, M.J.B., de Vries, A.A.F., 1999.
      Identification of a novel structural protein of arteriviruses. J. Virol. 73, 6335
      6345). The authors concluded that the 8 kDa protein is another arterivirus
      envelope protein and designated it E protein. However, we have not detected a
      significant level of an 8 kDa protein in LDV virions and thus conclude that it is
      not a structural virion component.

PMID- 11226574
TI  - Molecular characterization of the VP7 gene of Rotavirus isolated from a clinical
      sample of Calcutta, India.
AB  - The gene coding for outer capsid protein, VP7 of rotaviruses detected among the
      children suffering from watery diarrhea in the eastern part of India was studied.
      The full length gene, coding for VP7 was synthesized from a local strain, WD33,
      by combined reverse transcriptase-polymerase chain reaction. A total of 42 fecal
      RNA out of 93 rotavirus-positive samples hybridized with this DNA, indicating the
      prevalence of this strain in the community. Comparison of the nucleotide and
      deduced amino acid sequence with the VP7 gene of other serotypes revealed that
      the local strain,WD33, resembled closely with G1 serotype, the homology being 94
      and 97%, respectively. Multiplex PCR using the specific oligonucleotide primers
      also amplified the G1 specific DNA fragment. The overall change of 16 amino acids
      was noticed when compared with G1 specific prototype Wa strain of which nine
      amino acids are within the neutralization domain. However, the phylogenetic tree
      constructed by comparing the G1 strains from different countries demonstrated
      that this strain WD33 clustered as a distinct sub-lineage of lineage IV and not
      with Wa strain, that clustered with lineage III.

PMID- 11226575
TI  - Expression of deletion mutants of the hepatitis B virus protein HBx in E. coli
      and characterization of their RNA binding activities.
AB  - The hepatitis B virus protein HBx has been implicated in the development of liver
      cancer. It has been shown that the HBx protein is able to bind to single-stranded
      DNA in a specific manner. This DNA binding activity might be relevant for HBx
      oncogene character. To study the HBx interaction with nucleic acids in more
      detail we expressed full-length HBx as well as several N- and C-terminally
      truncated HBx proteins as 6xHis and GST-fusions in E. coli. Using a gel shift
      assay, we were able to demonstrate that all of the truncated HBx proteins have
      the ability to bind to an AU-rich RNA. The affinity of GST-HBx #3 (residues 80
      142) was an order of magnitude higher than that of GST-HBx #2 (residues 5-79),
      indicating that a high affinity RNA binding site is located in HBx C-terminal
      half. AUF1 is the protein ligand that binds to AU-rich RNA regions present in
      certain proto-oncogene mRNAs and causes their rapid degradation. By a competitive
      binding experiment of AUF1 and HBx to the AU-rich RNA oligonucleotide, we show
      that HBx is able to displace AUF1 from its binding site on the RNA
      oligonucleotide. This new aspect of HBx function is discussed in the context of
      cellular transformation.

PMID- 11226576
TI  - Modification of virus infectivity by cytoplasmic tail of HIV-1 TM protein.
AB  - Envelope glycoprotein incorporation is an essential process in formation of
      infectious particles of human immunodeficiency virus. Accumulated data have
      indicated that the cytoplasmic tail of Env gp41 is required for efficient
      incorporation. By analyzing mutant viruses with truncated cytoplasmic tails, we
      found that the domain was required in a cell-type-dependent manner for
      maintaining virus infectivity. Although the viruses with truncated cytoplasmic
      tails produced from HeLa, A3.01 and SupT1 cells showed a greatly reduced
      infectivity, those from SW480 and MT-4 cells retained a significant infectivity.
      To clarify the different effect of the cytoplasmic tail mutation on virus
      infectivity, we performed biochemical studies on the virions produced from HeLa
      and SW480 cells. Although the truncation of cytoplasmic tail appeared to reduce
      the Env incorporation in both cell lines, it caused a significant incorporation
      of Env precursor with HeLa cells. The results suggested that the cytoplasmic tail
      regulated selective incorporation of processed Env into virions in a cell-type
      dependent manner.

PMID- 11226577
TI  - Hepatitis C virus core protein potentiates c-Jun N-terminal kinase activation
      through a signaling complex involving TRADD and TRAF2.
AB  - The hepatitis C virus (HCV) core protein is a multifunctional viral nucleocapsid
      protein. Previously, it has been demonstrated that the HCV core protein interacts
      with the cytoplasmic domain of tumor necrosis factor receptor 1 (TNFR1). Since
      the TNFR1 is engaged in stimulation of transcriptional factor NF-kappaB and AP-1
      through activation of IkappaB kinase and c-Jun N-terminal kinase (JNK, or stress
      activated protein kinase), respectively, we have examined whether the interaction
      between core protein and TNFR1 can modulate JNK. In this study, we demonstrate
      that the HCV core protein synergistically activates TNFalpha-induced JNK at a
      core concentration dependent manner in human embryonic kidney (HEK) 293 cells.
      HCV core-mediated synergism of JNK activation was also detected in stable cells
      expressing HCV core protein. Furthermore, we demonstrate that HCV core protein
      does not compete with TNF receptor-associated death domain (TRADD) for its
      interaction with the death domain of TNFR1. Our in vivo data show that HCV core
      and TRADD form a ternary complex with TNFR1. These findings suggest that the HCV
      core protein modulates TNFR1 signaling and may, thus, play a role in chronic
      infection of HCV patients.

PMID- 11226578
TI  - Complete genome comparison of porcine reproductive and respiratory syndrome virus
      parental and attenuated strains.
AB  - Two full-length porcine reproductive and respiratory syndrome virus (PRRSV)
      genomes, strain VR-2332 and its cell culture passaged descendent RespPRRS vaccine
      strain, were compared and analyzed in order to identify possible sites of
      attenuation. Of the 44 nucleotide changes, 13 resulted in conservative changes
      and 18 produced non-conservative changes. The results suggest that key amino
      acids in ORF1 may contribute to the phenotype of RespPRRS, which includes
      increased growth rate on MA-104 cells and decreased virulence in swine. The
      results provide a genetic basis for future manipulation of a PRRSV reverse
      genetics system.

PMID- 11226579
TI  - Characterisation of the putative nucleoprotein gene of infectious salmon anaemia
      virus (ISAV).
AB  - A gene encoding the putative nucleoprotein (NP) of infectious salmon anaemia
      virus (ISAV), a commercially important salmonid Orthomyxovirus, has been
      identified. cDNA obtained from a subtractive cDNA library bound specifically to
      RNA extracted from ISAV-infected SHK-1 cell cultures. The 5' and 3' ends of the
      gene were amplified using RACE PCR and a full length open reading frame (ORF) of
      1851 nt identified encoding a predicted protein of 616 amino acids. No
      significant homology of this sequence with any other orthomyxovirus nucleoprotein
      was identifiable using BLAST or FASTA-based database searches. The ISAV-protein
      was however identified as a nucleoprotein based on its characteristic amino-acid
      composition. Furthermore the conserved sequence 5' GCAAAGA 3' was identified
      preceding the ORF, as has been identified in all other ISAV-genes characterised
      to date.

PMID- 11226580
TI  - Determination of the mutation rate of poliovirus RNA-dependent RNA polymerase.
AB  - The fidelity of poliovirus RNA-dependent RNA polymerase (3D(pol)) was determined
      using a system based on the fidelity of synthesis of the alpha-lac gene which
      codes for a subunit of beta-galactosidase. Synthesis products are screened for
      mutations by an alpha-complementation assay, in which the protein product from
      alpha-lac is used in trans to complement beta-galactosidase activity in bacteria
      that do not express alpha-Lac. Several polymerases have been analyzed by this
      approach allowing comparisons to be drawn. The assay included RNA synthesis by
      3D(pol) on an RNA template that coded for the N-terminal region of alpha-Lac. The
      product of this reaction was used as a template for a second round of 3D(pol)
      synthesis and the resulting RNA was reverse transcribed to DNA by MMLV-RT. The
      DNA was amplified by PCR and inserted into a vector used to transform Escherichia
      coli. The bacteria were screened for beta-galactosidase activity by blue-white
      phenotype analysis with white or faint blue colonies scored as errors made during
      synthesis on alpha-lac. Results showed a mutation rate for 3D(pol) corresponding
      to approximately 4.5x10(-4) errors per base (one error in approximately 2200
      bases). Analysis of mutations showed that base substitutions occurred with
      greater frequency than deletions and insertions.

PMID- 11226581
TI  - Localization of a new neutralizing epitope on the mumps virus hemagglutinin
      neuraminidase protein.
AB  - Four protein fragments which span the entire hemagglutinin-neuraminidase protein
      (HN) of mumps virus were expressed in HeLa cells and cell extracts were tested
      for their capability to induce neutralizing antibodies in mice. Fragment HN3 (aa
      213-372) was able to induce the production of hemagglutination-inhibiting and
      neutralizing antibodies. When a subfragment of HN3, the synthetic peptide
      NSTLGVKSAREF (aa 329-340 of HN) was used for immunization, hemagglutination
      inhibiting and neutralizing antibodies against mumps wild type virus but not
      against the Urabe Am9 vaccine virus were raised. The peptide could, therefore,
      contain a new epitope, which may be critical for protective host humoral immune
      response.

PMID- 11226582
TI  - Antigenic and genetic divergence of rabies viruses from bat species indigenous to
      Canada.
AB  - Antigenic characterisation of over 350 chiropteran rabies viruses of the
      Americas, especially from species reported rabid in Canada, distinguished 13
      viral types. In close accord with this classification, nucleotide sequencing of
      representative isolates, at both the N and G loci, identified four principal
      phylogenetic groups (I-IV), sub-groups of which circulated in particular bat
      species. Amongst the North American bat viruses, there was a notable division
      between group I specimens associated with colonial, non-migratory bats (Myotis
      sp. and Eptesicus fuscus) and those of group II harbored by solitary, migratory
      species (Lasiurus sp. and Lasionycteris noctivagans). Certain species of Myotis
      were clearly identified as rabies reservoirs, an observation often obscured
      previously by their frequent infection by viral variants of other chiroptera. An
      additional group (III) apparently circulates in E. fuscus, whilst viruses
      harbored by both insectivorous and haematophagus bats of Latin America clustered
      to a separate clade (group IV). Comparison of the predicted N and G proteins of
      these viruses with those of strains of terrestrial mammals indicated a similarity
      in structural organisation regardless of host species lifestyle. Finally, these
      sequences permitted examination of the evolutionary relationship of American bat
      rabies viruses within the Lyssavirus genus.

PMID- 11226583
TI  - Potyvirus proteins: a wealth of functions.

PMID- 11226584
TI  - Prevalence of antibodies to Sin Nombre virus in humans living in rural areas of
      southern New Mexico and western Texas.

PMID- 11226585
TI  - A heady message for lifespan regulation.
AB  - Mutant Caenorhabditis elegans in which the age-1 and daf-2 genes (involved in
      insulin-receptor-like signalling) are expressed at low levels exhibit extended
      lifespan. Wolkow and colleagues recently showed that restricted re-expression of
      age-1 and daf-2 genes in neurons of these mutants rescues wild-type lifespan as
      effectively as ubiquitous re-expression. Low levels of insulin-like signalling in
      neurons might control longevity by enhancing protection against free radical
      damage. However, in mammalian cells (including neurons) reduced insulin-like
      signalling is generally thought to be deleterious to antioxidant defence and to
      neuron survival. Here we discuss the new work and several hypotheses to explain
      this apparent contradiction.

PMID- 11226586
TI  - How many genes in Arabidopsis come from cyanobacteria? An estimate from 386
      protein phylogenies.
AB  - It is well known that chloroplasts and mitochondria donated many genes to nuclear
      chromosomes during evolution - but how many is "many"? A sample of 3961
      Arabidopsis nuclear protein-coding genes was compared with the complete set of
      proteins from yeast and 17 reference prokaryotic genomes, including one
      cyanobacterium (the lineage from which plastids arose). The analysis of 386
      phylogenetic trees distilled from these data suggests that between approximately
      400 (1.6%) and approximately 2200 (9.2%) of Arabidopsis nuclear genes stem from
      cyanobacteria. The degree of conservation preserved in protein sequences in
      addition to lateral gene transfer between free-living prokaryotes pose
      substantial challenges to genome phylogenetics.

PMID- 11226587
TI  - Were protein internal repeats formed by "bricolage"?
AB  - Is evolution an engineer, or is it a tinkerer--a "bricoleur"--building up complex
      molecules in organisms by increasing and adapting the materials at hand? An
      analysis of completely sequenced genomes suggests the latter, showing that
      increasing repetition of modules within the proteins encoded by these genomes is
      correlated with increasing complexity of the organism.

PMID- 11226588
TI  - Bringing gene order into bacterial shape.
AB  - A different arrangement of a cluster of genes involved in division and cell-wall
      synthesis separates bacilli from other bacteria in a phylogenetic analysis. We
      conclude that the relationships between these genes are not random and might
      reflect significant events in the evolution of the coupling between growth and
      division in bacteria.

PMID- 11226606
TI  - Did genomic imprinting and X chromosome inactivation arise from stochastic
      expression?
AB  - Both X chromosome inactivation and autosomal genomic imprinting generate a
      functional hemizygosity. Here we consider models that explain the evolution of
      genomic imprinting and X chromosome inactivation from novel perspectives.
      Specifically, we suggest that random (in)activation events are common in genes
      and gene clusters with a low probability of transcription. These generate
      variability that natural selection has acted on to evolve stable monoallelic
      expression. Possible selection forces might include a need for dosage
      compensation and the prevention of biallelic silencing where a total switch off
      would be lethal. Two different mechanisms can accomplish regular monoallelic
      expression - genomic imprinting and gene counting.

PMID- 11226607
TI  - Human morbid genetics revisited: relevance of epigenetics.
AB  - Identification of genes predisposing their carrier to complex diseases is a much
      more complicated task than finding genes involved in simple mendelian diseases.
      The slow progress in the genetic research of complex diseases could be due to
      limitations in the basic research strategy, which is almost exclusively
      orientated to the detection of disease-related DNA mutations or polymorphisms. I
      argue in this article that epigenetic misregulation of genes is more consistent
      with the features of complex diseases than is DNA sequence variation, and
      therefore that epigenetic factors could be important in understanding the origins
      of complex diseases.

PMID- 11226609
TI  - Manuscript evolution.
AB  - Frequently, letters, words and sentences are used in undergraduate textbooks and
      the popular press as an analogy for the coding, transfer and corruption of
      information in DNA. We discuss here how the converse can be exploited, by using
      programs designed for biological analysis of sequence evolution to uncover the
      relationships between different manuscript versions of a text. We point out
      similarities between the evolution of DNA and the evolution of texts.

PMID- 11226610
TI  - Does S. pombe exploit the intrinsic asymmetry of DNA synthesis to imprint
      daughter cells for mating-type switching?
AB  - Typically cell division is envisaged to be symmetrical, with both daughter cells
      being identical. However, during development and cellular differentiation,
      asymmetrical cell divisions have a crucial role. In this article, we describe a
      model of how Schizosaccharomyces pombe exploits the intrinsic asymmetry of DNA
      replication machinery--the difference between the replication of the leading
      strand and the lagging strand--to establish an asymmetrical mating-type switching
      pattern. This is the first system where the direction of DNA replication is
      involved in the formation of differentiated chromosomes. The discovery raises the
      possibility that DNA replication might be more generally involved in the
      establishment of asymmetric cellular differentiation.

PMID- 11226611
TI  - Genomic sequence analysis tools: a user's guide.
AB  - The wealth of information from various genome sequencing projects provides the
      biologist with a new perspective from which to analyze, and design experiments
      with, mammalian systems. The complexity of the information, however, requires new
      software tools, and numerous such tools are now available. Which type and which
      specific system is most effective depends, in part, upon how much sequence is to
      be analyzed and with what level of experimental support. Here we survey a number
      of mammalian genomic sequence analysis systems with respect to the data they
      provide and the ease of their use. The hope is to aid the experimental biologist
      in choosing the most appropriate tool for their analyses.

PMID- 11226613
TI  - Telehealth and the global health network in the 21st century. From homecare to
      public health informatics.
AB  - The Information Era we live in has created new challenges and opportunities. This
      age of information highways has an economic price, which has not been properly
      evaluated. Detailed studies are needed to prove the cost and medical
      effectiveness of these technologies as well as its effects in the quality of
      life. Our society's future may depend on it. People are living longer,
      discoveries in genetics and in information technology are not only helping
      produce newer drugs faster but also providing the opportunity to exploit new
      areas such as disease prevention. These technologies provide a variety of
      opportunities to address public health challenges such as universal access for
      the uneducated, counter-bioterrorism, telemedicine, distance education, and home
      care. These opportunities present new challenges such as: surveillance,
      privacy/confidentiality/security of personal information which will affect all of
      our lives. No strategy has been presented publicly (yet) addressing (neither) the
      benefits (n)or the pitfalls of such technologies. From an economic point of view
      it is an imperative necessity to understand the importance of the Information
      Technology Infrastructure (ITI) and what it is. The investments in creating and
      maintaining this ITI will not come from a single application area such as
      healthcare, but rather from a combination of sources such as electronic commerce,
      banking, financial, manufacturing, entertainment, travelling, weather
      forecasting, pharmaceuticals, education, defence and many other 'industries' or
      application areas.

PMID- 11226614
TI  - Telehealth: 'real life' implementation issues.
AB  - This paper addresses the practical issues specific to the successful integration
      of telehealth into the Canadian health system at national, regional, provincial
      and territorial levels. Five key issues for optimal implementation were readiness
      of the environment; needs analysis/strategic business plans/diverse partnerships;
      equipment and Information Technology (IT) vendors; staged implementation; and
      evaluation. Strong professional, as well as technical policy standards, were also
      required. Recognizing the importance of human factors and workforce implications,
      the change process, and the changing culture were also viewed as critical to
      successful implementation. The importance of 'best practices', 'lessons learned',
      'buy-in', inter-connectivity, inter-operability, and sustainability issues was
      noted. Lastly, ongoing systemic evaluation was seen to be key to sustained
      telehealth programs.

PMID- 11226615
TI  - Web-based telemedicine systems for home-care: technical issues and experiences.
AB  - The use of the Web for telemedicine applications seems nowadays a compulsory
      solution: the Web has become a standardized infrastructure for giving access to
      sophisticated telemedicine applications from virtually any machine and operating
      system. Such standardized communication platform guarantees accessibility and
      usability advantages to both customers and providers (patients and physicians).
      However, there are several issues that should be discussed in depth, with
      particular reference to all the applications related to the provision of care at
      distance, nowadays called telecare applications. In telecare applications the
      role of the patient becomes central, since he/she is actively involved in the
      process of managing care and treatments, and since he/she (or his/her families)
      is responsible for collecting some measurements and related information. In this
      paper we will discuss the general architectural and technical issues related to
      the development of Web-based systems for telecare applications, relying on the
      experience we gained within the telecare project T-IDDM (Telematic Management of
      Insulin Dependent Diabetes Mellitus), devoted to assist the management and home
      monitoring of Type 1 Diabetes Mellitus patients.

PMID- 11226616
TI  - Tele-rheumatology: telephone follow up and cyberclinic.
AB  - This paper reviews here the main practical applications of telemedicine with
      particular reference to telephone care by health professionals to patients. A
      pilot project of out-patient telephone follow-up service for continuity of
      ambulatory rheumatology patients is described and recommendations are provided
      for those keen to develop such a service. In a later section newer technologies
      such as the potential practical applications of the internet and e-mail are
      described with the setting up of a cyber project for rheumatology and
      osteoporosis patients. It is noted that despite enthusiasm and development of
      such new projects, conventional clinicians need further longer term observation
      to grasp the advantages and pitfalls before more widespread use of telemedicine
      becomes commonplace.

PMID- 11226617
TI  - Paperless practice -- electronic medical records at Island Health.
AB  - A computerised general medical practice using electronic medical records is
      described. Issues including security, confidentiality, shared access to records,
      use of knowledge bases and decision support are discussed. The practice has
      electronic data interchange links with local hospitals and health authorities.
      The practice has demonstrated increased clinical effectiveness, improved primary
      care team working and cost savings on administrative and clerical tasks.

PMID- 11226618
TI  - Optimisation and evaluation of an asynchronous transfer mode teleradiology co
      operative system: the experience of the EMERALD and the BONAPARTE projects.
AB  - This paper describes the work carried out to optimise and evaluate in clinical
      routine a multimedia telemedicine application for co-operative imaging diagnosis.
      This research has been attained within the framework of two European research
      projects, namely the EMERALD [1] and the BONAPARTE [2]. A user-centred
      telemedicine application was developed on an existing advanced broadband
      multimedia teleradiology platform to exploit the possibilities offered by
      Asynchronous Transfer Mode (ATM) technology to support real-time teleconsultation
      services for medical imaging. The evaluation of this telemedicine system in both
      projects has been performed with the aim of (1) characterising and optimising the
      ATM teleradiology platform, minimising the bandwidth requirements without
      degrading the quality of service offered to users and (2) evaluating the
      telemedicine system usability to improve the fulfillment of user's needs. The
      assessment outcomes have provided insights into technical limitations of
      broadband multimedia technologies for an optimum usage of a teleradiology co
      operative diagnosis systems and the organisational difficulties and limitations
      involved in setting-up these new advanced telemedicine services to achieve the
      expected clinical benefits.

PMID- 11226619
TI  - Evaluating telemedicine in an accident and emergency setting.
AB  - This paper outlines the methodology of an evaluation of telemedicine in an
      Accident and Emergency (A&E) setting. Telemedicine technology consisting of ISDN
      2 based videoconferencing and 'store & forward' software has been installed and
      is currently being evaluated in two minor injury units (MIUs) and a District
      General Hospital (DGH) A&E department in Lincolnshire. A cost-benefit analysis
      will be conducted using a pragmatic prospective case-control study with both a
      concurrent and retrospective control group. Any differences in resource use
      (including direct and indirect costs) between the intervention (Telemedicine) and
      the control (No Telemedicine) groups will be identified from both a patient and
      NHS perspective. A variety of health and non-health outcome measures will be
      recorded including staff and patient acceptability of the new technology.

PMID- 11226620
TI  - Legal ethical and risk issues in telemedicine.
AB  - This paper summarizes the main topics of discussion at a workshop hosted by the
      Centre for Law Ethics and Risk in Telemedicine at the 2nd International
      Conference on Advances in the Delivery of Care, held at the Institute of Health
      Sciences, City University, London from Wednesday 24 to Friday 26 March 1999. The
      workshop offered a unique opportunity for practitioners in the fields of
      telemedicine and shared care to discuss the legal, ethical and risk issues
      arising from the practice of medicine and healthcare from a distance using
      information and communication technologies ('ICTs') with a panel of experts from
      the fields of medicine, law, insurance and risk management. There was a broad
      consensus that many of the legal and ethical issues raised by those who dislike
      the idea of treating distant patients were not specific to telemedicine but to
      medicine and healthcare in general. It was agreed, however, that in those areas
      where telemedicine does create new clinical risks and responsibilities a much
      more proactive role should be taken by the professional associations and Royal
      Colleges in providing better education and guidance to their members about the
      practical and professional issues that will inevitably arise from the evolution
      of 'Hospitals Without Walls'.

PMID- 11226621
TI  - An improved surface-based method for DNA computation.
AB  - DNA computing is a novel method for solving a class of intractable computational
      problems, in which the computing time can grow exponentially with problem size.
      Up to now, many accomplishments have been achieved to improve its performance and
      increase its reliability, among which a surface-based method is an efficient
      candidate. In this paper, the surface-based approach proposed by Liu, Q., Wang,
      L., Frutos, A.G., Condon, A.E., Corn, R.M., and Smith, L.M., 2000, DNA computing
      on surfaces. Nature 403, 175-179 is analyzed and an improved surface-based method
      for DNA computation (i.e. the hybrid DNA/optical computing method) is proposed.
      Compared with Liu et al.'s approach, our method has some significant advantages
      such as low cost, short operating time, reusable surface and simple experimental
      steps. Moreover, the concept of combining easily patterned DNA computing steps
      with equally parallel, but generally uniform and not easily patterned optical
      computing steps is an important new direction.

PMID- 11226622
TI  - The cortico-basal ganglia-thalamocortical circuit with synaptic plasticity. II.
      Mechanism of synergistic modulation of thalamic activity via the direct and
      indirect pathways through the basal ganglia.
AB  - A possible mechanism underlying the modulatory role of dopamine, adenosine and
      acetylcholine in the modification of corticostriatal synapses, subsequent changes
      in signal transduction through the "direct" and "indirect" pathways in the basal
      ganglia and variations in thalamic and neocortical cell activity is proposed.
      According to this mechanism, simultaneous activation of dopamine D1/D2 receptors
      as well as inactivation of adenosine A1/A(2A) receptors or muscarinic M4/M1
      receptors on striatonigral/striatopallidal inhibitory cells can promote the
      induction of long-term potentiation/depression in the efficacy of excitatory
      cortical inputs to these cells. Subsequently augmented inhibition of the activity
      of inhibitory neurons of the output nuclei of the basal ganglia through the
      "direct" pathway together with reduced disinhibition of these nuclei through the
      "indirect" pathway synergistically increase thalamic and neocortical cell firing.
      The proposed mechanism can underlie such well known effects as "excitatory" and
      "inhibitory" influence of dopamine on striatonigral and striatopallidal cells,
      respectively; the opposite action of dopamine and adenosine on these cells;
      antiparkinsonic effects of dopamine receptor agonists and adenosine or
      acetylcholine muscarinic receptor antagonists.

PMID- 11226623
TI  - Modeling insulin kinetics: responses to a single oral glucose administration or
      ambulatory-fed conditions.
AB  - This paper presents a nonlinear mathematical model of the glucose-insulin
      feedback system, which has been extended to incorporate the beta-cells' function
      on maintaining and regulating plasma insulin level in man. Initially, a
      gastrointestinal absorption term for glucose is utilized to effect the glucose
      absorption by the intestine and the subsequent release of glucose into the
      bloodstream, taking place at a given initial rate and falling off exponentially
      with time. An analysis of the model is carried out by the singular perturbation
      technique in order to derive boundary conditions on the system parameters which
      identify, in particular, the existence of limit cycles in our model system
      consistent with the oscillatory patterns often observed in clinical data. We then
      utilize a sinusoidal term to incorporate the temporal absorption of glucose in
      order to study the responses in the patients under ambulatory-fed conditions. A
      numerical investigation is carried out in this case to construct a bifurcation
      diagram to identify the ranges of parametric values for which chaotic behavior
      can be expected, leading to interesting biological interpretations.

PMID- 11226624
TI  - A computational model of membrane lipid electronic properties in relation to
      neural signaling.
AB  - We present a computational model of a transiently-organized neural membrane
      molecular system with possible information-processing capacity. The model
      examines field-induced dipole and quadrupole moments and polarizability in
      monomeric, dimeric, and trimeric ethenes. Polarization of the ethenes is strongly
      indicated. This result is interpreted as a significant electronic feature of a
      molecular computing system based on organization of membrane lipids into a
      transient ( approximately 10(-4) s) crystalline state due to lipid-protein
      hydrophobic mismatch at the membrane-ion-channel interface. Predictive
      implications of the model's electronic features are briefly discussed.

PMID- 11226625
TI  - A single-fractal analysis of cellular analyte-receptor binding kinetics utilizing
      biosensors.
AB  - A fractal analysis of a confirmative nature only is presented for cellular
      analyte-receptor binding kinetics utilizing biosensors. Data taken from the
      literature can be modeled by using a single-fractal analysis. Relationships are
      presented for the binding rate coefficient as a function of the fractal dimension
      and for the analyte concentration in solution. In general, the binding rate
      coefficient is rather sensitive to the degree of heterogeneity that exists on the
      biosensor surface. It is of interest to note that examples are presented where
      the binding coefficient, k exhibits an increase as the fractal dimension (D(f))
      or the degree of heterogeneity increases on the surface. The predictive
      relationships presented provide further physical insights into the binding
      reactions occurring on the surface. These should assist in understanding the
      cellular binding reaction occurring on surfaces, even though the analysis
      presented is for the cases where the cellular "receptor" is actually immobilized
      on a biosensor or other surface. The analysis suggests possible modulations of
      cell surfaces in desired directions to help manipulate the binding rate
      coefficient (or affinity). In general, the technique presented is applicable for
      the most part to other reactions occurring on different types of biosensor or
      other surfaces.

PMID- 11226626
TI  - Photoinduced transformation of 14-F-bacteriorhodopsin gelatin films based on both
      wild type and D96N mutant.
AB  - Spectral and kinetic transformations were studied in gelatin films made with 14-F
      wild type (WT) bacteriorhodopsin (BR) and 14-F D96N mutant BR. Unlike the recent
      study of water suspensions of the same pigments, where a red shifted species at
      660 nm was shown to form under the light in 14-F WT only, there are no drastic
      differences in photoinduced behavior between gelatin films based on 14-F WT and
      14-F D96N. It is not observed any photoinduced formation of red shifted species
      at 660 nm for both types of films as it is observed for corresponding pigments in
      water suspension. The observed results are explained in a terms of relationship
      between the rates of two photoinduced processes that occur in suspensions and
      films of corresponding pigments. Kinetic characteristics of the photoinduced
      processes for the films with chemical additives suggest that there are no
      advantages in using 14-F D96N films when compared to films based on 14-F WT.

PMID- 11226627
TI  - Continuous growth of autocatalytic sets.
AB  - We investigated a topology of the reaction network for polymerization of amino
      acids as the emergence and the continuous growth of autocatalytic sets. Reaction
      networks including transpeptidation reaction can yield newer and longer peptides
      with time having higher concentrations. Conditions necessary for the occurrence
      of transpeptidation can be met in actual amino acid/peptide systems.

PMID- 11226628
TI  - Day/night variations of dopamine ocular content during Xenopus laevis ontogeny.
AB  - Concentration of dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid
      is quantified by high-pressure liquid chromatography with a coulometric detection
      system in the eye of Xenopus laevis through ontogeny and in adults at two times
      during photocycle (midday and midnight). Ocular dopaminergic activity remains low
      during pre- and prometamorphosis and significantly rises in postmetamorphic
      froglets. This increase is more pronounced at midnight than at midday. The
      dualism of DA content versus DA release in Xenopus ocular tissue is studied in an
      eyecup culture system. On a 24-h cycle of DA release from adult Xenopus eyecups
      the highest DA release by eyecups is produced during daytime, and significantly
      decreases in darkness. From these results it can be concluded that in spite of
      the early development of the retinal dopaminergic system in the ontogeny of
      Xenopus, the final maturation must occur during the metamorphic climax.
      Endogenous DA release is significantly inhibited by light offset, which explains
      the higher ocular DA content found at midnight as compared to midday in
      postmetamorphic froglets and adults.

PMID- 11226629
TI  - Nitric oxide augments voltage-activated calcium currents of crustacea (Idotea
      baltica) skeletal muscle.
AB  - Invertebrate skeletal muscle contraction is regulated by calcium influx through
      voltage-dependent calcium channels in the sarcolemmal membrane. In present study
      we investigated the effects of nitric oxide (NO) donors on calcium currents of
      single skeletal muscle fibres from the marine isopod, Idotea baltica, using two
      electrode voltage clamp recording techniques. The NO donors, S-nitrosocysteine, S
      nitroso-N-acetyl-penicillamine or hydroxylamine reversibly increased calcium
      inward currents in a time dependent manner. The increase of the current was
      prevented by methylene blue. Our experiments suggest that NO increases calcium
      inward currents. NO, by acting on calcium ion channels in the sarcolemmal
      membrane, therefore, may directly be involved in the modulation of muscle
      contraction.

PMID- 11226630
TI  - Metabotropic glutamate receptor 8 in the rat hippocampus after pilocarpine
      induced status epilepticus.
AB  - The expression of metabotropic glutamate receptor 8 (mGluR8) was studied in the
      rat hippocampus after pilocarpine-induced status epilepticus (APISE) by light
      immunohistochemistry and immunoelectron microscopy. At 1 day APISE, mGluR8
      immunoreactivity was up-regulated in the entire molecular layer of the dentate
      gyrus. At 7 days APISE, mGluR8 immunoreactive cells began to appear in the
      stratum lacunosum moleculare of CA1, and by day 31, they were seen in all layers
      of CA1. By electron microscopy and double labelling study, the mGluR8
      immunoreactive cells were identified as astrocytes. The present novel finding of
      induced expression of mGluR8 in astrocytes APISE suggests that it may be linked
      to gliosis.

PMID- 11226631
TI  - Dysfunctional mitochondrial respiration in the wobbler mouse brain.
AB  - The involvement of mitochondrial dysfunction promoting neurodegenerative
      diseases, including amyotrophic lateral sclerosis (ALS), has been suggested.
      Histopathological and biochemical mitochondrial abnormalities have been reported
      in both sporadic and familial patients and suggest the contention that
      mitochondria may play a key role promoting ALS. Animal models of ALS provide a
      unique opportunity to study this incurable and fatal human disease. In the
      present study we tested the hypothesis that alterations in mitochondrial
      physiology occur in the brain of wobbler mice. No significant difference was
      found in the respiratory control index or adenosine diphosphate/oxygen ratio
      values between isolated mitochondria of wobbler and control mice. When pyruvate
      and malate were used as substrates, oxygen consumption was decreased
      significantly by approximately 33% in mitochondria isolated from wobbler mouse
      brain compared to controls. Oxygen consumption in the presence of ascorbate and
      N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) was decreased significantly by
      approximately 21% in wobbler brain mitochondria compared to controls, which
      suggests impairment in the function of complex IV. These findings are the first
      demonstration of mitochondrial respiratory chain dysfunction in the brain of the
      wobbler mouse.

PMID- 11226632
TI  - Long-term potentiation in hippocampus of rats is enhanced by endogenous
      acetylcholine in a way that is independent of N-methyl-D-aspartate receptors.
AB  - By using extracellular recordings of field potential, the exact pathway by which
      the endogenous ACh influencing the induction of long-term potentiation (LTP) in
      CA1 area was analysed in slices of rat hippocampus. The results showed that: (1)
      the application of (-) huperzine A, an AChE inhibitor extracted from Chinese herb
      Qian Ceng Ta (Huperzia Serrata), could enhance the induction of LTP, while this
      drug showed little effect on the second components of multiple population spikes
      that were recorded in Mg(2+)-free medium and had proven to be N-methyl-D
      aspartate (NMDA) receptor-mediated response; and (2) scopolamine, a muscarinic
      receptor antagonist, could significantly suppressed the induction of LTP, while
      most of the suppressive effect of scopolamine was blocked when slices were
      pretreated by bicuculline, a gamma-aminobutyric acid (GABA(A)) receptor
      antagonist. These results suggest that endogenous ACh potentiates the induction
      of LTP through the inhibition of GABAergic interneurons that modulate pyramidal
      neurons, but not through the activation of NMDA receptors located on pyramidal
      neurons.

PMID- 11226633
TI  - Orally administered atropine enhances motor cortex excitability: a transcranial
      magnetic stimulation study in human subjects.
AB  - Oral application of atropine was used to test if a modulation of cholinergic
      neurotransmission changed motor excitability. Healthy volunteers received either
      1 or 2 mg atropine. Paired transcranial magnetic stimulation was used to study
      intracortical inhibition and intracortical facilitation before, 1 h and 24 h
      after ingestion of atropine. In addition, the silent period, motor threshold, F
      wave and motor response amplitudes were measured. The 1 mg dose of atropine
      induced a loss of intracortical inhibition, the 2 mg dose produced an
      intracortical disinhibition and enhanced intracortical facilitation. These
      changes returned to baseline after 24 h. Other electrophysiological parameters
      remained unchanged. Thus, an antagonist of pre- and postsynaptic muscarinic
      receptors increased excitability in the human motor cortex in a dose-dependent
      manner, indicating an influence of the cholinergic system on motor cortex
      excitation.

PMID- 11226634
TI  - Distribution of novel RFamide-related peptide-like immunoreactivity in the mouse
      central nervous system.
AB  - Recently, novel mammalian RFamide-related peptides (RFRPs) have been identified
      and suggested to increase prolactin release in the rodent. To assess possible
      functions of RFRPs, we investigated the distribution of RFRPs in the mouse
      central nervous system by immunochemical analyses. The quantitative analysis
      revealed that the concentration of RFRP-like substances was much higher in the
      brainstem and spinal cord than in other regions. Immunohistochemistry showed that
      RFRP-like immunoreactive perikarya were localized in the dorsomedial hypothalamic
      nucleus, the lateral superior olive, and the nucleus of the solitary tract. The
      dense networks of immunoreactive fibers were found in the lateral parabrachial
      nucleus, the lateral reticular nucleus, and the superficial layer of spinal
      trigeminal nucleus and dorsal horn of the spinal cord. Thus, RFRPs may
      participate not only in neuroendocrine functions but also in behavioral, sensory,
      and autonomic functions.

PMID- 11226635
TI  - Differential increase in cerebrospinal fluid-acetylcholinesterase after treatment
      with acetylcholinesterase inhibitors in patients with Alzheimer's disease.
AB  - The clinical significance and the effects of pharmacological treatment of
      patients with Alzheimer's disease (AD) were evaluated by measurement of
      acetylcholinesterase (AChE) in the cerebrospinal fluid (CSF). CSF-AChE of AD
      patients was lower, not significantly, compared with controls. However, CSF-AChE
      was significantly increased after treatment of AD patients with AChE inhibitors
      (donepezil and galantamine). The increase was higher in patients treated with
      donezepil than in those treated with galantamine, which might be related to
      different mechanisms for the substances. The increase was also dose-dependent,
      and was especially marked in patients showing a clinical response. These data
      suggest that CSF biomarkers are capable not only of identifying a biochemical
      effect of drugs, but also of differentiating between different compounds in a
      dose-dependent manner.

PMID- 11226636
TI  - Neurodevelopmental consequences of gestational exposure (GD14-GD20) to low dose
      deltamethrin in rats.
AB  - Effect of low level in utero exposure to deltamethrin (DT) (1mg /kg wt.) during
      gestation day 14-20 was studied on selected neurobehavioral, neurochemical,
      immunohistochemical parameters in rats at 6 and 12 weeks postnatal period. The
      significant increase in acetylcholinesterase activity and decrease in (3)H
      quinuclidinyl benzilate binding in the hippocampal region of DT exposed animals,
      suggesting impairment in cholinergic (muscarinic) receptors. A significant
      decrease in the learning and memory performances was also observed both at 6 and
      12 weeks, which is directly correlated with decrease in muscarinic receptor
      binding. Immunohistochemistry and image analysis of growth associated protein-43,
      a neuron specific protein present in axonal growth cone and a marker for neuronal
      differentiation and synaptogenesis, exhibit aberrant increase in its expression
      in the hippocampus in DT exposed rats at both time periods. The data suggests
      that low level exposure to DT in utero during brain growth spurt period adversely
      affects the developing brain and the changes persist even up to 12 weeks
      postnatal period in rats. Although there is no significant recovery at 12 weeks
      assessment but still significant impairment persist on biochemical and
      behavioural parameters.

PMID- 11226637
TI  - Requirement of neural activity for the maintenance of dopaminergic neurons in rat
      midbrain slice cultures.
AB  - Chronic treatment of organotypic midbrain slice cultures with L-type Ca(2+)
      channel blocker nicardipine (3-10 microM) or verapamil (10 microM) for 18 days
      resulted in a drastic decrease in the number of dopaminergic neurons. A voltage
      dependent Na(+) channel blocker tetrodotoxin (1 microM) was also effective in
      decreasing the number of dopaminergic neurons. Concurrent application of
      forskolin (20 microM) or dibutyryl cyclic AMP (1 mM) counteracted the effects of
      nicardipine and tetrodotoxin. These results suggest that spontaneous neuronal
      activity within midbrain slice cultures, causing Ca(2+) influx through L-type
      Ca(2+) channels that maintains intracellular cyclic AMP levels, is required for
      the maintenance of dopaminergic neurons.

PMID- 11226638
TI  - Prepro-orexin mRNA levels in the rat hypothalamus, and orexin receptors mRNA
      levels in the rat hypothalamus and adrenal gland are not influenced by the
      thyroid status.
AB  - Orexins are two recently discovered neuropeptides that play an important role in
      the regulation of food intake and in the regulation of the sleep-wake cycle. In
      this work we examined the effects of thyroid hormones on prepro-OX expression in
      the rat hypothalamus, and OXRs expression in the rat hypothalamus and adrenal
      gland. Hypo- and hyperthyroidism were induced in adult male rats, and the levels
      of hypothalamic prepro-OX and OXRs mRNA, and adrenal OXRs mRNA were determined
      using semiquantitative reverse transcription-polymerase chain reaction and/or in
      situ hybridization. Our results indicate that thyroid status affects neither
      prepro-OX in the hypothalamus nor hypothalamic and adrenal gland OXRs expression.

PMID- 11226639
TI  - Dual effects of melatonin on barbiturate-induced narcosis in rats.
AB  - Melatonin affects the circadian sleep/wake cycle, but it is not clear whether it
      may influence drug-induced narcosis. Sodium thiopenthal was administered
      intraperitoneally into male rats pre-treated with melatonin (0.05, 0.5, 5 and 50
      mg/kg). Melatonin pre-treatment affected in a dual manner barbiturate narcosis,
      however, no dose-effect correlation was found. In particular, low doses reduced
      the latency to and prolonged the duration of barbiturate narcosis. In contrast,
      the highest dose of melatonin (50 mg/kg) caused a paradoxical increase in the
      latency and produced a sustained reduction of the duration of narcosis, and a
      reduction in mortality rate. Melatonin 0.5 and 5 mg/kg influenced the duration
      but not the latency of ketamine- or diazepam-induced narcosis. Thus, the dual
      action of melatonin on pharmacological narcosis seems to be specific for the
      barbiturate mechanism of action.

PMID- 11226641
TI  - Integrity of the blood-cerebrospinal fluid barrier in early Parkinson's disease.
AB  - Dysfunction of the blood-cerebrospinal fluid barrier (BCB) has been implicated in
      the pathogenesis of Parkinson's disease (PD) and other neurodegenerative
      disorders. Therefore, we assayed serum and cerebrospinal fluid (CSF) from 30
      parkinsonian patients and 30 controls for concentrations of albumin and IgG. The
      CSF/serum ratio for albumin (AQ), IgG (GQ), IgG-index as well as determination of
      oligoclonal bands were used to evaluate BCB function and to quantify humoral
      immune response within the central nervous system (CNS). Levels of AQ, GQ and IgG
      index did not significantly differ in both groups. We found no dysfunction of the
      blood-CSF barrier or signs of local synthesis of IgG in the central nervous
      system of parkinsonian patients. Our data do not support the hypothesis of a
      dysfunctional BCB that contributes to pathophysiological mechanisms underlying
      PD.

PMID- 11226640
TI  - Glial cell line-derived neurotrophic factor in the substantia nigra from control
      and parkinsonian brains.
AB  - Glial cell line-derived neurotrophic factor (GDNF) was measured for the first
      time in the brain (substantia nigra, caudate nucleus, putamen, cerebellum, and
      frontal cortex) from control and parkinsonian patients by highly sensitive
      sandwich enzyme-linked immunosorbent assay. In both groups, the levels of GDNF in
      the various brain regions were lower (pg/mg protein) than those of brain-derived
      growth factor (ng/mg order), and were significantly higher in the nigro-striatal
      dopaminergic regions (substantia nigra, caudate nucleus, putamen) than in the
      cerebellum and frontal cortex (P < 0.05). However, the content of GDNF in the
      dopaminergic regions showed no significant difference between parkinsonian and
      control patients.

PMID- 11226642
TI  - Decrease of muscarinic M2 cholinoceptor gene expression in the heart of aged rat.
AB  - It is well known that the baroreflex activity decreases with aging. However, the
      mechanisms of this change are still not clear. Thus, we investigated one of the
      parameters to see whether aging alters gene expression of muscarinic receptors in
      the heart of Wistar rat aged between 2 months (adult) and 24 months (aged). The
      mRNA level determination by Northern blot analysis for muscarinic M2
      cholinoceptors in aged rat was decreased as compared to that in 2-month-old rats.
      Quantification of receptor protein using selective antibodies indicated that the
      level of muscarinic M2 cholinoceptor in the heart of 24-month-old rats was lower
      than that in 2-month-old animals. These results indicate the decrease of
      muscarinic M2 cholinoceptor in heart with aging that may contribute as one of the
      parameters for dysfunction in baroreflex activity.

PMID- 11226643
TI  - Do burn patients need burn specific multidisciplinary outpatient aftercare:
      research results.
AB  - In a cross-sectional study of patients 12-24 months after a burn injury, the need
      for a multidisciplinary burn specific outpatient clinic was examined in relation
      to aftercare consumption, physical and psychological problems. Four hundred and
      twenty nine patients were assessed by means of three self-report questionnaires:
      IES, SCL(PTSD-SL) and BSHS-SV-S. Results indicated that the current aftercare
      providers are almost exclusively medical doctors and that a quarter of the
      patients are dissatisfied with received aftercare. However, dissatisfaction about
      current aftercare was not the only criterion to determine whether patients wanted
      burn-specific aftercare. The severity of psychological and physical problems
      predicted interest in a multi-disciplinary outpatient clinic. Self-reported
      psychological and physical problems were found to be related to one another.
      Univariate logistic regression outcomes suggested that patients with serious
      psychological and physical problems are more likely to express interest in a burn
      specific outpatient clinic, but that, in a multivariate regression analysis,
      physical problems and psychological problems measured on the SCL(PTSD-SLEEP) do
      not contribute to the prediction of the interest in a burn-specific outpatient
      clinic anymore once symptoms of PTSD are taken care of. Results suggest that
      psychological aftercare for burn patients needs to be improved. Possible steps to
      improve aftercare to meet patients' needs are discussed.

PMID- 11226644
TI  - Clinical outcome of HIV positive patients with moderate to severe burns.
AB  - Human immunodeficiency virus (HIV) infection is a world wide and growing problem.
      Little is found in the literature concerning the treatment and outcome of
      patients suffering from HIV infection who are treated for burns. The aim of this
      study was to assess whether the outcome of HIV positive patients suffering from
      burn wounds differed from those who do not have HIV infection. Thirty three
      patients formed the HIV positive study group. HIV negative controls were matched
      for age, degree of burns, sex and inhalation injury. The mean age of the patients
      was 31.6 years and the mean total body surface burn was 26.4%. There was no
      significant difference in the outcome of the two groups in terms of mortality or
      treatment parameters measured. Two patients had stigmata of AIDS (tuberculosis)
      and both died. One patient, with a CD4 count of 228, developed severe necrotizing
      fasciitis. In keeping with other studies looking at the outcome of HIV positive
      patients in an Intensive Care Unit setting, we concluded that a HIV positive
      patient, who suffers from a burn wound and has no stigmata of AIDS, should be
      treated similarly to a HIV negative patient.

PMID- 11226645
TI  - Pediatric burn injuries in Tehran, Iran.
AB  - The objective of this study was to identify the epidemiologic features of
      pediatric burn injuries in western Tehran. Study subjects included all children
      up to the age of 15 years who were treated as inpatients at the Tohid Burn Center
      in Tehran between April 1995 and March 1998. Among the 3341 burns admitted to the
      Center over the 3-year study period, 1454 (43.5%) occurred in children less than
      16 years of age. The overall case fatality rate for children was 16%, while the
      annual burn incidence rates ranged from 22.7 to 17.8 burns per 100000 child
      years. The overall gender ratio (boys/girls) was 2.6. Children less than 2 years
      of age had the highest burn incidence and burn mortality rates. These findings
      will be used as a basis for developing targeted preventive programs to protect
      Iranian children from burns.

PMID- 11226646
TI  - An epidemiological study of 1063 hospitalized burn patients in a tertiary burns
      centre in Hong Kong.
AB  - A total of 1063 acute burn patients were admitted to the Burns Unit of Prince of
      Wales Hospital, Hong Kong between March 1993 and February 1999. There were 678
      males and 385 females with a male to female ratio of 1.76:1. The median age was
      13.1 year-old and the median burn size was 6% total body surface area (TBSA).
      Pediatric patients under the age of 15 year-old accounted for 550 (51.7%)
      admissions and 235 (42.7%) of them were toddlers <2 year-old, while adult
      patients of age above 15 year-old accounted for the other 513 (48.3%) admissions.
      There was no seasonal variation in admission. Domestic burns resulted in 756
      (71.1%) injuries followed by industrial burns that caused 175 (16.5%) admissions.
      The median hospital stay was 9 days and 54 patients (5.1%) had inhalation injury
      requiring intubation and ventilatory support. Twenty-four patients died in this
      series which yielded a mortality rate of 2.3%. The median age for this mortality
      group was 46.6 year-olds with a median extent of burns of 68% TBSA. There were 16
      males and 8 females with a male to female ratio of 2:1. Eighteen (75%) patients
      had flame burns and 15 (83.3%) of them had inhalation injury. The mortality group
      had significantly larger burn size (P<0.001), higher incidence of inhalation
      injury (P<0.001) and older age (P<0.001) compared to the survivors.

PMID- 11226647
TI  - Suicidal burns in Hong Kong Chinese.
AB  - There were 1063 acute burn patients admitted to the Burns Unit of Prince of Wales
      Hospital, Hong Kong, between March 1993 and February 1999. Eleven patients (1%)
      were burned due to attempted suicide. Seven were males and four were females,
      with a male:female ratio of 1.75:1. The median age was 38 years (range: 20-49
      years) and the median extent of the burns was 55% total body surface area (range:
      1-95%). Ten patients (90.9%) were self-incinerated and one patient attempted
      suicide by jumping into a hot bath. Seven patients (63.6%) suffered from severe
      smoke inhalation injury that required immediate intubation for ventilatory
      support. The average number of operations for the survivors was 3.7 (range: 0-8)
      and their median hospital stay was 42 days (range: 2-92 days). Four patients
      (36.4%) died from their injuries. Suicidal burns were more common among
      unemployed males with a history of psychiatric illness and substance abuse. Town
      gas (naphtha: a mixture of 49% hydrogen, 28.5% methane, 19.5% carbon dioxide and
      3.0% carbon monoxide) was the most frequently used agent for self-immolation
      because it is probably the most convenient source of a fire accelerant in Hong
      Kong. Compared to the general burn population, this suicide group had a larger
      extent of burns, higher incidence of inhalation injury, required more operative
      treatment and longer hospital stay with a higher mortality rate.

PMID- 11226648
TI  - Type III secretion/intoxication system important in virulence of Pseudomonas
      aeruginosa infections in burns.

PMID- 11226649
TI  - Multi-drug resistant Pseudomonas aeruginosa outbreak in a burns unit--an
      infection control study.
AB  - A newly introduced, multi-drug resistant (MDR) strain of Pseudomonas aeruginosa
      was isolated from four patients admitted to the Concord Hospital Burns Unit (BU)
      between December 1997 and March 1998. It was the cause of recurrent episodes of
      bacteraemia in two. This strain was resistant in vitro to gentamicin,
      piperacillin and ciprofloxacin. The isolates were confirmed as a clonal strain by
      pulse field gel electrophoresis (PFGE). Multiple environmental swabs were taken
      to search for an environmental reservoir, but no source was identified. Random
      cultures of staff members' hands failed to demonstrate ongoing carriage. In the
      absence of a demonstrable point source for the outbreak, direct cross
      transmission patient to patient, via transient staff hand contamination, was the
      most likely route of infection. Following study commencement no new cases of
      infection with the MDR strain were detected. It would appear that the infection
      cycle has been interrupted, and the outbreak terminated following the discharge
      of the last infected patient from the BU. Contamination of a neutral detergent in
      the BU with Klebsiella oxytoca was detected incidentally during environmental
      surveillance. A potential hospital-wide outbreak was averted.

PMID- 11226650
TI  - Microbiologic aspects of predominant bacteria isolated from the burn patients in
      Korea.
AB  - The risk of infection in burns is well-known. In recent decades, the
      antimicrobial resistance of bacteria isolated from burn patients has increased.
      For this reason, we have carried out a study of the predominant bacterial
      profiles and antimicrobial resistance patterns of isolates from a burn center in
      Korea. A retrospective study was undertaken at Hallym University, Hangang Sacred
      Heart Hospital to examine the bacterial isolates from the burn patients and to
      compare the antibiograms of the predominant bacteria isolated from these patients
      with those of the other wards over a period of 3 years. Pseudomonas aeruginosa
      was the most common (n=2997, 45.7%) isolate from the burn patients followed by
      Staphylococcus aureus (n=21261, 19.2%) and Acinetobacter baumannii (n=878,
      13.4%). These bacteria, isolated from the burn patients, were almost all higher
      in antimicrobial resistance rate than those in the non-burn patients (P<0.05).
      Because these bacteria showed very high resistant rates, they must be avoided in
      order to control a hospital-acquired infection. Our results seem helpful in
      providing useful guidelines for choosing effective empiric antimicrobial therapy
      against bacteria isolated from the burn patients in Korea.

PMID- 11226651
TI  - Acinetobacter baumannii--an emerging nosocomial pathogen in the burns unit
      Manipal, India.
AB  - A retrospective study on 113 patients admitted to the burns unit over a period of
      12 months was undertaken to investigate the emerging trend of Acinetobacter
      baumannii infection. Wound infection with A. baumannii was seen in 13 (11.5%)
      patients. Of these six (46%) patients developed septicaemia with the same
      bacteria and five (38%) expired. The virulence of these bacteria, drug
      susceptibility pattern and its role as a nosocomial pathogen is discussed.

PMID- 11226652
TI  - Effects of early enteral feeding on the prevention of enterogenic infection in
      severely burned patients.
AB  - The aim of the study was to analyse the effects of early enteral feeding on the
      prevention of enterogenic infection in severely burned patients. A total of 22
      patients with severe burns were randomly divided into an early enteral feeding
      group (EF) and a delayed enteral feeding group (DF). The levels of serum
      endotoxin and TNF-alpha were dynamically detected in the members of both groups,
      and two unmetabolized sugars (lactulose and mannitol) were orally administered to
      these patients 1, 3 and 5 days postburn. Intestinal permeability was evaluated by
      detecting the concentrations of lactulose and mannitol in the urine and the
      lactulose-mannitol ratio (L/M) ratio. The levels of serum endotoxin and TNF-alpha
      in severely burned patients were significantly higher than in normal subjects
      (P<0.01). The endotoxin level was positively related to the TNF-alpha level
      (rEF=0.93, P<0.01; rDF=0.80, P<0.05). The urinary lactulose levels in both groups
      were significantly higher than in normal (P<0.01), the urinary mannitol levels
      showed no obvious changes (P>0.05). The urinary L/M ratios in both groups were
      significantly higher than in normal subjects (P<0.01). The urinary L/M ratio was
      positively related to the serum endotoxin level (r=0.95, P<0.01). The urinary
      lactulose levels and the urinary L/M ratios in the EF group were significantly
      lower than in the DF group (P<0.01). The levels of serum endotoxin and TNF-alpha
      in the EF group were significantly lower than in the DF group (P<0.01). It is
      suggested that intestinal permeability was markedly higher after burns than
      normal, and was positively related to the gut-derived endotoxemia. Early enteral
      feeding may decrease intestinal permeability, preserve the intestinal mucosal
      barrier and have a beneficial effect on the reduction of enterogenic infection.

PMID- 11226653
TI  - Acellular allograft dermal matrix: immediate or delayed epidermal coverage?
AB  - In a prospective, randomized study seventeen patients received skin grafts to a
      freshly excised burn wound. One group was grafted with a deantigenized dermal
      matrix and immediately overgrafted with thin autograft. The second group was
      grafted with dermal matrix, which was then covered with bank allograft for
      protection, and autografted 1 week later. Each group also received a standard
      split thickness control graft. Assessment was carried out for up to 1 year. There
      were no statistically significant differences of graft take between any of the
      groups, or in the Vancouver scar score at follow-up. Thin donor sites used for
      dermal matrix coverage healed faster than standard control graft sites, P<0.001.
      Immediate grafting of acellular dermal matrix with thin autograft works well and
      leads to an acceptable late result, with faster donor site healing than standard
      split thickness grafts.

PMID- 11226654
TI  - Burn depth and its histological measurement.
AB  - This paper describes a new technique for burn depth measurement, based on the
      histological assessment of dermal microvascular occlusion in burn biopsies. The
      technique was validated in a preliminary study of acute progressive microvascular
      damage in five adults with partial thickness burns. Burn depth was calculated at
      three time points post burn from the mean histological measurement of the most
      superficial patent and the deepest blocked vessels in five separate sections from
      each biopsy. The results were expressed as a percentage of the total dermal
      thickness and correlated well with the laser Doppler measurement of dermal blood
      flow and clinical estimation of burn depth. The reproducibility of the technique
      was tested by the repeated blind analysis of five randomly chosen biopsies on a
      separate occasion. Altman-Bland plot analysis demonstrated a median variation of
      0.1% (95% confidence interval -1 to 2%). A second independent observer (MPHT),
      who carried out a blind analysis of the same randomly chosen biopsies, tested the
      precision of the technique. The median variation was 2% (95% confidence interval 
      5 to 8.5%).

PMID- 11226655
TI  - Arterial thermodilution: an alternative to pulmonary artery catheter for cardiac
      output assessment in burn patients.
AB  - STUDY OBJECTIVE: To study the agreement between cardiac output measurements with
      the pulmonary artery catheter and with the transpulmonary thermodilution
      technique in patients with burns. DESIGN: Prospective, clinical study. PATIENTS:
      23 patients with serious burns and an abbreviated burn severity index score
      (ABSI)>6. SETTING: intensive care unit for severely burned in a burn center in
      Germany. RESULTS: A total number of 218 cardiac output measurements obtained
      during the first 72 h postburn were analysed. In the pulmonary artery group, mean
      cardiac index was 3.93 l/min/m2 and ranged from 0.96 to 9.58. In the
      transpulmonary group the cardiac index measurements ranged from 0.96 to 9.61 with
      a mean of 4.0 l/min/m2. During the entire observation period cardiac index was
      consistently higher in the transpulmonary group than in the pulmonary artery
      group with a bias of 0.32 l/min/m2 and a standard deviation (S.D.) of 0.29
      l/min/m2. Linear regression analysis revealed
      CI(arterial)=0.98xCI(pulm)+0.22l/min/m2 (r=0.9678, P<0.038). Bias and precision
      to each time point according to Bland and Altman demonstrated a good agreement
      between both techniques. CONCLUSION: The transpulmonary thermodilution offers an
      attractive, less invasive alternative to the pulmonary artery catheter in
      patients with burns. Arterial thermodilution for CO measurements is as precise as
      PA thermal dilution, and CO(pulm) can be replaced by CI(arterial) when basic
      methodological principles are respected.

PMID- 11226656
TI  - A newly developed hydrofibre dressing, in the treatment of partial-thickness
      burns.
AB  - A newly developed, carboxymethylcellulose based hydrofibre dressing, Aquacel, was
      tested for the treatment of partial thickness burns. In this study 84 patients
      with mainly partial thickness burns were included, 76 patients received 1 or 2
      days pre-treatment with a topical antimicrobial agent. Clinical behaviour showed
      a strong resemblance with cadaver skin treatment with respect to adherence to the
      wound. Adverse reactions, incidence of clinical wound infection, healing time and
      the need for wound excision and grafting were analysed, as was the final outcome
      using the 'Vancouver Scar Scale'. The mean size of the wounds treated with the
      hydrofibre dressing was 6.0% body surface area (min: 1%, max: 18%). Two patients
      clinically showed signs of a wound infection during treatment, but in general
      wound cultures were low or negative. In 42 patients (50%) the wounds healed
      completely within 10 days, in six patients (7%) small defects remained that
      healed by further treatment with a topical antimicrobial cream. In 36 patients
      (43%) excision and grafting of the remaining deeper parts of the wounds was
      performed as this is the standard therapy in the centre for all burned areas that
      have not healed within 2-3 weeks post-injury. The extent of the surgical
      procedures was limited since 66.1% of the wound area had healed already at the
      end of the hydrofibre treatment. In 54 patients the outcome of the treatment
      after 2-3 months was analysed by means of the Vancouver Scar Scale, which showed
      favourable results in general, and especially for patients who did not require
      surgery. Compared to earlier experience with allograft skin it was concluded that
      hydrofibre dressing is a safe, suitable and easy to use material for treatment of
      partial thickness burns.

PMID- 11226657
TI  - Recontruction of facial defects and burn scars using large size freehand full
      thickness skin graft from lateral thoracic region.
AB  - Reconstruction of facial defects due to trauma, burn scar and congenital
      deformities is very challenging for reconstructive surgeons. Although many
      alternative techniques have been suggested, the ideal technique has not been
      described yet. Full-thickness skin grafting procedures are one of the options,
      but when larger grafts are needed, donor site morbidity is problematic. Full
      thickness skin graft harvested from lateral thoracic region has some advantages
      for face reconstruction with its larger size, similar colour, thickness, skin
      quality and texture.

PMID- 11226658
TI  - Chryseobacterium in burn wounds.
AB  - Chryseobacteria are gram negative organisms, formerly known as Flavobacteria,
      which rarely cause infections of burn wounds. This article documents three cases
      of Chryseobacterium infection in burn wounds and adds to the other two cases that
      have been reported in English literature. Two patients died, with one of the
      deaths linked to a Chryseobacteria bacteraemia. In two patients, there was an
      associated history of first aid treatment with untreated water. Patients whose
      burn wounds are suspected to be infected with Chryseobacterium require wound
      excision and coverage in combination with antibiotic therapy such as
      ciprofloxacin, vancomycin and rifampicin.

PMID- 11226659
TI  - Current attitudes to burns resuscitation in the UK.
AB  - In recent years, much discussion has occurred regarding the efficacy and safety
      of using albumin as part of burns resuscitation regimes. The discussion was
      fuelled in 1998 by the publication of the findings of the Cochrane Injuries Group
      Albumin Reviewers, Br Med J 1998; 317: 235-240. The current usage of human
      albumin solutions as part of the burn resuscitation regimes of burns units in the
      UK was assessed by telephone questionnaire by contacting medical staff from all
      the burns units in the UK that admit burn patients for resuscitation. Knowledge
      of the albumin controversy, details of their current resuscitation regimes and
      recent or planned changes were included in the questionnaire, Most individuals
      were aware of the albumin controversy. A total of eight units had made changes to
      their resuscitation regimes since July 1998, although five were still using
      albumin. Four more were considering making changes, while 13 units that had been
      using albumin prior to the controversy had made no changes at all. Only three
      units had stopped using albumin-based colloid altogether. Only one unit was not
      using albumin prior to the controversy. The implications of these results and
      possible ways forward are discussed.

PMID- 11226660
TI  - Povidone-iodine related burns.
AB  - Skin preparation burns associated with chemical agents are uncommon. They occur
      most frequently in patients placed in the lithotomic position undergoing
      gynaecologic or urologic operations, the burn being on the buttocks, and in those
      undergoing orthopaedic operations, the burn being on the extremities and under a
      tourniquet. The basic mechanism involves irritation coupled with maceration and
      pressure. If the betadine solution has not been allowed to dry and has been
      trapped under the body of the patient in a pooled dependent position, such as the
      buttocks or under a tourniquet, the solution may irritate the skin and result in
      a skin burn. The irritation coupled with pressure leads to a situation analogous
      to that seen in the development of an acute accelerated decubitus ulcer;
      irritation, maceration, friction and pressure compounding each other to result in
      a skin burn or superficial ulcer in the skin. Our experience with three
      illustrative patients who presented with various burns following exposure to
      povidone-iodine (betadine) is described below.

PMID- 11226661
TI  - Failure to clear casts and secretions following inhalation injury can be
      dangerous: report of a case.
AB  - A 27-year-old man suffered smoke inhalation during a fire. Three days later, he
      complained of respiratory difficulty and was admitted to our hospital.
      Bronchoscopy revealed a very large buildup of sputum mixed with soot extending
      from the left main bronchus to the bifurcation of the upper and lower lobe
      bronchi and causing both pulmonary atelectasis and pneumonia. The debris was
      successfully removed the next day with basket forceps via bronchoscopy. The
      patient's airway pressure dropped significantly, enabling extubation almost
      immediately. Because of the possibility for respiratory failure caused by viscous
      secretion, it is important to perform initial bronchoscopy in cases of suspected
      inhalation injury.

PMID- 11226662
TI  - Is 20 years of immobilization, not sufficient to render metacarpophalangeal
      joints completely useless?--Correction of a 20-year old post-burn palmar
      contracture: a case report.
AB  - This report presents a case of post-burn palmar contracture with flexion
      contracture of thumb of 20-year duration. The contracture was released and the
      raw area was covered with split thickness skin graft. Only one 'K' wire in soft
      tissue was needed to keep all the fingers straight and immobilized, suggestive of
      intermetacarpal ligamentous contracture. A static night splint was given to
      maintain the correction. Complete range of movement was achieved in a month with
      the combination of dynamic splinting and physiotherapy. It was interesting to
      note that even 20 years of contracted position did not render the
      metacarpophalangeal joints completely stiff and useless. Probable reasons are
      discussed.

PMID- 11226663
TI  - Burn injuries caused by air bag deployment.
AB  - Automobile air bags have gained acceptance as an effective measure to reduce the
      morbidity and mortality associated with motor vehicle accidents. As more cars
      have become equipped with them, new problems have been encountered that are
      directly attributable to the deployment of the bag itself. An increasing variety
      of associated injuries has been reported, including minor burns. We present two
      automobile drivers who were involved in front-impact crashes with air bag
      inflation. They sustained superficial and partial-thickness burns related to the
      deployment. The evaluation of these cases shows mechanisms involved in burn
      injuries caused by the air bag system. Most of the burns are chemical and usually
      attributed to sodium hydroxide in the aerosol created during deployment. Also
      direct thermal burns from high-temperature gases or indirect injuries due to the
      melting of clothing, as well as friction burns from physical contact are
      possible. However, the inherent risks of air bag-related burns are still
      outweighed by the benefits of preventing potentially life-threatening injuries.

PMID- 11226664
TI  - Longstanding pigmentary changes in paediatric scalds dressed with a non-adherent
      siliconised dressing.
AB  - The non-adherent siliconised dressing Mepitel is excellent for burns, especially
      in children. It provides a moist wound environment, promotes wound healing and is
      easy and relatively painless to use. However, surgeons should be aware that in
      black children its use has been associated with pigmentation abnormalities.

PMID- 11226665
TI  - Bilateral olfactory deprivation reveals a selective noradrenergic regulatory
      input to the olfactory bulb.
AB  - Unilateral olfactory deprivation in the rat induces changes in the
      catecholaminergic system of the olfactory bulb. Nevertheless, evidence suggests
      that unilateral deprivation does not fully prevent stimulation of the deprived
      bulb. The present report analyses the response of the catecholaminergic system of
      the olfactory bulb in fully deprived rats obtained by bilateral naris occlusion.
      The complete deprivation produces more rapid and dramatic changes in both the
      intrinsic and extrinsic catecholaminergic systems of the olfactory bulb.
      Intrinsic responses involve a rapid decrease in dopamine-containing cells to
      about 25% of controls, correlated with a decreased Fos expression in
      juxtaglomerular cells of all olfactory glomeruli, with the only exception of
      those of the atypical glomeruli which maintain unaltered expression of both
      markers. In parallel with these events, there is a progressive increase in the
      density of extrinsic noradrenergic axons arising from neurons in the locus
      coeruleus, which shows, in parallel, a progressive increase in Fos expression.
      This model demonstrates plastic changes in the catecholaminergic system of the
      olfactory bulb forming a valid morphological substrate for lowering thresholds in
      the processing of olfactory information. In addition to this generalized
      response, there is another one, directed to a specific subset of olfactory
      glomeruli (atypical glomeruli) involved in the processing of odor pheromone-like
      cues related to behavioral responses, that could be responsible for keeping
      active this reduced and selected group of glomeruli carrying crucial olfactory
      information. These results indicate the existence of adaptive changes in the
      catecholaminergic system of the olfactory bulb as a response to the lack of
      afferent peripheral stimulation. These changes involve dopamine- and
      noradrenaline-immunoreactive elements, in a strategy presumably directed at
      maintaining to the highest possible level the ability to detect olfactory
      signals.

PMID- 11226666
TI  - Olfactory learning induces differential long-lasting changes in rat central
      olfactory pathways.
AB  - In the present work, we investigated lasting changes induced by olfactory
      learning at different levels of the olfactory pathways. For this, evoked field
      potentials induced by electrical stimulation of the olfactory bulb were recorded
      simultaneously in the anterior piriform cortex, the posterior piriform cortex,
      the lateral entorhinal cortex and the dentate gyrus. The amplitude of the evoked
      field potential's main component was measured in each site before, immediately
      after, and 20 days after completion of associative learning. Evoked field
      potential recordings were carried out under two experimental conditions in the
      same animals: awake and anesthetized. In the learning task, rats were trained to
      associate electrical stimulation of one olfactory bulb electrode with the
      delivery of sucrose (positive reward), and stimulation of a second olfactory bulb
      electrode with the delivery of quinine (negative reward). In this way,
      stimulation of the same olfactory bulb electrodes used for inducing field
      potentials served as a discriminative cue in the learning paradigm. The data
      showed that positively reinforced learning resulted in a lasting increase in
      evoked field potential amplitude restricted to posterior piriform cortex and
      lateral entorhinal cortex. In contrast, negatively reinforced learning was mainly
      accompanied by a decrease in evoked field potential amplitude in the dentate
      gyrus. Moreover, the expression of these learning-related changes occurred to be
      modulated by the animals arousal state. Indeed, the comparison between
      anesthetized versus awake animals showed that although globally similar, the
      changes were expressed earlier with respect to learning, under anesthesia than in
      the awake state. From these data we suggest that associative olfactory learning
      involves different neural circuits depending on the acquired value of the
      stimulus. Furthermore, they show the existence of a functional dissociation
      between anterior and posterior piriform cortex in mnesic processes, and stress
      the importance of the animal's arousal state on the expression of learning
      induced plasticity.

PMID- 11226667
TI  - Changes of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptors in
      layer V of epileptogenic, chronically isolated rat neocortex.
AB  - In vivo chronic partial isolation of neocortical islands results in
      epileptogenesis that involves pyramidal neurons of layer V. To test whether an
      alteration in glutamate receptors might contribute to the epileptiform activity,
      we analysed the time-course of light microscopic changes in expression of alpha
      amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors using subunit-specific
      antibodies. The isolation caused a rapid down-regulation of immunoreactivity for
      GluR1 and GluR2/3 subunits in deep layer V pyramidal neurons within the
      neocortical island which was evident 24h post-lesion, and within three days was
      reduced to about 40-60% of the control level. Many pyramidal cells in deep layer
      V completely lacked GluR2. Between one and four weeks of survival, down
      regulation of GluR2/3 and GluR2 involved the majority of pyramidal layer V
      neurons, except for cells in the upper part of layer V, and those within narrow
      areas of all sub-laminae of layer V ("micro-islands"). Initial down-regulation
      was also observed one to three days post-lesion for subunits 1 and 2 of the N
      methyl-D-aspartate receptor, but in contrast to GluR2/3 immunoreactivity,
      NMDAR2A/B immunoreactivity was enhanced three weeks post-lesion. The present data
      provide evidence for plastic changes in glutamate receptors in neurons of
      partially isolated neocortical island. A sub-population of layer V neurons
      remains relatively unaffected, and would presumably be capable of generating fast
      glutamatergic synaptic potentials necessary for the development of synchronous
      epileptiform activity.

PMID- 11226668
TI  - Intra- and inter-areal connections between the primary visual cortex V1 and the
      area immediately surrounding V1 in the rat.
AB  - We have qualitatively and quantitatively analysed the anatomical connections
      within and between rat primary visual cortex (V1) and the rim region surrounding
      area V1, using both ortho- and retrograde anatomical tracers (biotinylated
      dextran amine, biocytin, cholera toxin b subunit). From the analysis of the
      projection patterns, and with the assumption that single points in the rat visual
      cortex, as in other species, have projection fields made up of multiple patches
      of terminals, we have concluded that just two V1 recipient areas occupy the
      entire rim region: an anterolateral area, probably homologous with V2 in other
      mammals, previously named Oc2L, and a medial area, corresponding to Oc2M. A non
      reciprocal projection from the anterolateral area to the medial area was
      identified. Small injections (300-600microm uptake zone diameter) of the
      anatomical tracers in area V1, or in the rim region, label orthograde intra-areal
      connections from each injection site to offset small patches. This is found in
      all regions of the rim and within at least the relatively expanded central dorsal
      field representation of V1. From the extent of these projections in V1 and the
      two rim regions, we have estimated that the neurons at the injection site send
      diverging laterally spreading projections to other neurons whose receptive fields
      share any part of the area included in the pooled receptive fields of the neurons
      at the injection site. Orthogradely labelled inter-areal feedforward projections
      from V1 to either rim region are estimated to diverge in their projections to
      neurons that share any part of the area of the pooled receptive fields of the V1
      intra-areal connectional field of the same injection. The orthogradely labelled
      feedback projections to V1, from injection sites in either rim region, reach V1
      neurons whose pooled receptive fields match those of the neurons in the rim
      injection site, i.e. with no divergence. Despite patchy anatomical connectional
      fields, our estimates indicate that visual space is represented continuously in
      the receptive fields of neurons postsynaptic to each intra- or inter-areal field
      of orthograde label. We suggest that, despite the absence of regularly mapped
      functions in rat V1 (e.g. regularly arranged orientation specificity), which in
      other species (e.g. primates and cats) relate to the patchy connectional
      patterns, the rat visual cortex intra- and inter-areal anatomical connections
      follow similar patterns and scaling factors to those in other species.

PMID- 11226669
TI  - Persistent sodium channel activity mediates subthreshold membrane potential
      oscillations and low-threshold spikes in rat entorhinal cortex layer V neurons.
AB  - Entorhinal cortex layer V occupies a critical position in temporal lobe circuitry
      since, on the one hand, it serves as the main conduit for the flow of information
      out of the hippocampal formation back to the neocortex and, on the other, it
      closes a hippocampal-entorhinal loop by projecting upon the superficial cell
      layers that give rise to the perforant path. Recent in vitro electrophysiological
      studies have shown that rat entorhinal cortex layer V cells are endowed with the
      ability to generate subthreshold oscillations and all-or-none, low-threshold
      depolarizing potentials. In the present study, by applying current-clamp, voltage
      clamp and single-channel recording techniques in rat slices and dissociated
      neurons, we investigated whether entorhinal cortex layer V cells express a
      persistent sodium current and sustained sodium channel activity to evaluate the
      contribution of this activity to the subthreshold behavior of the cells. Sharp
      electrode recording in slices demonstrated that layer V cells display
      tetrodotoxin-sensitive inward rectification in the depolarizing direction,
      suggesting that a persistent sodium current is present in the cells. Subthreshold
      oscillations and low-threshold regenerative events were also abolished by
      tetrodotoxin, suggesting that their generation also requires the activation of
      such a low-threshold sodium current. The presence of a persistent sodium current
      was confirmed in whole-cell voltage-clamp experiments, which revealed that its
      activation "threshold" was negative by about 10mV to that of the transient sodium
      current. Furthermore, stationary noise analysis and cell-attached, patch-clamp
      recordings indicated that whole-cell persistent sodium currents were mediated by
      persistent sodium channel activity, consisting of relatively high-conductance (
      approximately 18pS) sustained openings. The presence of a persistent sodium
      current in entorhinal cortex layer V cells can cause the generation of
      oscillatory behavior, bursting activity and sustained discharge; this might be
      implicated in the encoding of memories in which the entorhinal cortex
      participates but, under pathological situations, may also contribute to
      epileptogenesis and neurodegeneration.

PMID- 11226670
TI  - Kainate-induced seizures alter protein composition and N-methyl-D-aspartate
      receptor function of rat forebrain postsynaptic densities.
AB  - The postsynaptic density is a highly dynamic structure, which is reorganized in
      an activity-dependent manner. An animal model for temporal lobe epilepsy, i.e.
      kainate-induced limbic seizures in rats, was used to study changes in
      postsynaptic density composition after extensive synaptic activity. Six hours
      after kainate injection, the protein content of the postsynaptic density
      fractions from rats that developed strong seizures was increased three-fold
      compared to saline-treated controls. Immunoblot analysis revealed that the
      relative amounts of metabotropic glutamate receptor 1alpha, N-ethylmaleimide
      sensitive fusion protein, protein kinases C, Fyn and TrkB, as well as the
      neuronal nitric oxide synthase, were significantly higher in seizure-developing
      than in control rats. In contrast, the relative contents of the kainate receptor
      KA2 subunit, beta-actin, alpha-adducin and the membrane-associated guanylate
      kinase homolog SAP90/PSD-95 were decreased. The relative amounts of additional
      postsynaptic density proteins, including alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate and N-methyl-D-aspartate receptor subunits,
      calcium/calmodulin-dependent kinase type II, casein kinase 2, tubulin,
      microtubule-associated protein 2B, the membrane-associated guanylate kinase
      homolog SAP102, and proline-rich synapse-associated protein 1/cortactin binding
      protein 1/Shank2 remained essentially unchanged. To assess possible changes in
      postsynaptic performance, postsynaptic densities were isolated from control and
      epileptic rats, incorporated into giant liposomes and N-methyl-D-aspartate
      receptor currents were recorded. A significant reduction in the mean conductance
      was observed in patches containing postsynaptic densities from animals with high
      seizure activity. This was due to the presence of reduced conductance levels in
      each membrane patch compared to control postsynaptic density preparations. From
      these data, we suggest that intense synaptic activity associated with seizures
      modifies the composition of postsynaptic densities and has profound consequences
      on the function of the N-methyl-D-aspartate receptors present in them. This
      rearrangement may accompany impairment of synaptic plasticity.

PMID- 11226672
TI  - Effects of early environment on granule cell morphology in the dentate gyrus of
      the guinea-pig.
AB  - The aim of the present study was to determine whether early environment affects
      the morphology of the dentate gyrus granule cells in the guinea-pig, a rodent
      whose brain is at an advanced stage of maturation at birth. Male and female
      guinea-pigs were assigned at six to seven days of age to either a control
      (social) or an isolated environment where they remained for 80-90 days. The
      dendritic tree and somata of the granule cells were quantified in Golgi-Cox
      stained brains. The granule cells of isolated males had fewer dendritic branches
      and a shorter dendritic length than those of control males in the inner two
      thirds of the dendritic tree, but a larger number of branches and a larger
      dendritic length in the distal one-fourth. In contrast, the granule cells of
      isolated females had a larger number of branches and a larger dendritic length
      than control females in the inner one-half of the dendritic tree and a reduced
      number of branches and a shorter dendritic length in the distal one-fourth. The
      granule cell somata were smaller in isolated than in control males. No such
      difference was observed in females. Sex differences were found in the granule
      cell morphology. In the control environment, the granule cells of males had more
      branches and a greater dendritic length in the inner one-half of the dendritic
      tree than those of females but fewer dendritic branches and a shorter dendritic
      length in the distal one-fourth. In the isolated environment, the granule cells
      of males had fewer branches and a shorter dendritic length in the inner two
      thirds of the dendritic tree than females, but more dendritic branches and a
      greater dendritic length in the distal one-fourth. In the control environment
      male granule cells had a larger soma than those of females. The opposite occurred
      in the isolated environment. The results of this study indicate that early
      isolation induces remarkable structural changes in the granule cells of the
      dentate gyrus in a rodent whose brain is at an advanced stage of maturation at
      birth. They also indicate that the effects of environment are different at
      different levels of the dendritic tree and in the two sexes.

PMID- 11226671
TI  - Chronic nicotine exposure reduces N-methyl-D-aspartate receptor-mediated damage
      in the hippocampus without altering calcium accumulation or extrusion: evidence
      of calbindin-D28K overexpression.
AB  - Neuronal accumulation of excess Ca2+ has been implicated in cellular death
      following several forms of physical and chemotoxic insult. Recent studies have
      suggested that exposure to agonists at brain nicotinic acetylcholine receptors
      reduces cytotoxic consequences of increased intracellular Ca2+ following some
      insults. In the present study, the ability of chronic exposure to (-)-nicotine to
      reduce cytotoxicity and attenuate increases in intracellular Ca2+ caused by
      exposure to N-methyl-D-aspartate were examined in organotypic cultures of rat
      hippocampus. Cultures were exposed to nicotine (0.1-10.0 microM) for five days
      prior to excitotoxic insult with N-methyl-D-aspartate. Exposure to N-methyl-D
      aspartate produced concentration-dependent increases in both accumulation of 45Ca
      and in early and delayed cell death in the CA1, CA3 and dentate gyrus regions of
      cultures. The CA1 region of the hippocampus displayed the greatest sensitivity to
      cytotoxic effects of N-methyl-D-aspartate exposure; however, this regional
      difference was not associated with increased accumulation of 45Ca. Prior exposure
      to nicotine markedly attenuated N-methyl-D-aspartate-induced early and delayed
      cell death in each hippocampal region at concentrations as low as 0.1microM.
      However, nicotine did not alter the initial N-methyl-D-aspartate-stimulated
      influx of 45Ca or enhance extrusion of accumulated 45Ca measured at several time
      points after insult. Five days of exposure to nicotine markedly increased
      immunoreactivity of the Ca2+ binding protein calbindin-D28K in each region of
      hippocampal cultures, effects reduced by mecamylamine co-exposure. These findings
      suggest that the potent protective effects of chronic nicotine exposure against
      neuronal overexcitation are not likely attributable to attenuations of Ca2+
      accumulation, but are likely related to increased buffering of accumulated Ca2+.

PMID- 11226673
TI  - Presynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor
      mediated stimulation of glutamate and GABA release in the rat striatum in vivo: a
      dual-label microdialysis study.
AB  - The existence of presynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionate (AMPA)-type glutamate autoreceptors on glutamate nerve terminals in
      vitro has recently been demonstrated using synaptosomal and brain slice
      preparations. In the present study we have used a modification of a rapid dual
      label intracerebral microdialysis method, previously developed by Young and co
      workers(80,81) for the study of presynaptic mechanisms of neurotransmitter
      release, to investigate whether presynaptic AMPA receptors also play a role in
      the control of striatal glutamate release in vivo. For comparative purposes, the
      action of locally applied AMPA on striatal GABA release in vivo was also
      monitored. Local application of AMPA (0.01-100 microM), by reverse dialysis, into
      the striatum resulted in concentration-dependent increases in the Ca(2+)
      dependent efflux of both [3H]L-glutamate and [14C]GABA. Maximum responses reached
      142.0+/-6.5% and 166.8+/-7.7% of basal efflux for [3H]L-glutamate and [14C]GABA,
      respectively. No marked behavioural changes were observed at any dose of the
      agonist. Unexpectedly, the AMPA-evoked responses were not potentiated by the AMPA
      receptor desensitization inhibitors cyclothiazide (10-100microM) or aniracetam
      (1mM). Consistent with this finding, AMPA-stimulated [3H]L-glutamate and
      [14C]GABA efflux were significantly attenuated by co-perfusion with the
      selective, competitive AMPA receptor antagonist 6-nitro-7
      sulphamoylbenzo(F)quinoxaline-2,3-dione (100microM) but not 1-(aminophenyl)-4
      methyl-7,8-methylendioxy-5H-2,3-benzodiazepine (100microM), a non-competitive
      AMPA receptor antagonist known to interact with the cyclothiazide site to control
      AMPA receptor function. The broad spectrum ionotropic glutamate receptor
      antagonist, kynurenic acid (100-1000microM) also markedly inhibited the AMPA
      evoked responses in the striatum in vivo. None of the antagonists, when given
      alone, influenced basal efflux of [3H]L-glutamate suggesting a lack of tonic
      regulatory control of glutamate release via presynaptic AMPA-type autoreceptors
      in the rat striatum. These results demonstrate the presence of presynaptic AMPA
      receptors, of a novel cyclothiazide- and aniracetam-insensitive subtype, on
      presynaptic nerve terminals in the rat striatum in vivo, acting to enhance
      glutamate and GABA release. Our data support the concept of AMPA receptor
      heterogeneity in vivo, a finding which may facilitate the development of novel,
      more selective drugs for the treatment of a range of neurological disorders
      associated with abnormal cerebral glutamate release. The pharmacological profile
      of these novel presynaptic receptors is currently under investigation.

PMID- 11226674
TI  - Nigral neurotensin receptor regulation of nigral glutamate and nigroventral
      thalamic GABA transmission: a dual-probe microdialysis study in intact conscious
      rat brain.
AB  - Dual-probe microdialysis in the awake rat was employed to investigate the effects
      of intranigral perfusion with the tridecapeptide neurotensin on local dialysate
      glutamate and GABA levels in the substantia nigra pars reticulata and on
      dialysate GABA levels in the ventral thalamus. Intranigral neurotensin (10-300nM,
      60min) dose-dependently increased (+29+/-3% and +46+/-3% vs basal for the 100 and
      300nM concentrations, respectively) local dialysate glutamate levels, while the
      highest 300nM concentration of the peptide exerted a long-lasting and prolonged
      reduction in both local and ventral thalamic (-20+/-4% and -22+/-2%,
      respectively) GABA levels. Intranigral perfusion with the inactive neurotensin
      fragment neurotensin(1-7) (10-300nM, 60min) was without effect. Furthermore, the
      non-peptide neurotensin receptor antagonist SR 48692 (0.2mg/kg) and tetrodotoxin
      (1microM) fully counteracted the intranigral neurotensin (300nM)-induced increase
      in local glutamate. SR 48692 (0.2mg/kg) also counteracted the decreases in nigral
      and ventral thalamic GABA release induced by the peptide. In addition,
      intranigral perfusion with the dopamine D(2) receptor antagonist raclopride
      (1microM) fully antagonized the neurotensin (300nM)-induced decreases in nigral
      and ventral thalamic GABA levels. The ability of nigral neurotensin receptor
      activation to differently influence glutamate and GABA levels, whereby it
      increases nigral glutamate and decreases both nigral and ventral thalamic GABA
      levels, suggests the involvement of neurotensin receptor in the regulation of
      basal ganglia output at the level of the nigra.

PMID- 11226675
TI  - Glutamate regulates the spontaneous and evoked release of dopamine in the rat
      striatum.
AB  - Resting and evoked extracellular dopamine levels in the striatum of the
      anesthetized rat were measured by fast-scan cyclic voltammetry in conjunction
      with carbon fiber microelectrodes. Identification of the substance detected in
      vivo was achieved by inspection of background-subtracted voltammograms.
      Intrastriatal microinfusion of kynurenate, a broad-spectrum antagonist of
      ionotropic glutamate receptors, caused a decrease in the resting extracellular
      level of dopamine. The kynurenate-induced decrease was unaffected by systemic
      pretreatment with pargyline, an inhibitor of monoamine oxidase, but was
      significantly attenuated by systemic pretreatment with alpha-methyl-p-tyrosine,
      an inhibitor of tyrosine hydroxylase. Although glutamate by itself did not affect
      resting extracellular dopamine levels, glutamate did attenuate the kynurenate
      induced decrease. Kynurenate decreased dopamine release in response to electrical
      stimulation of the medial forebrain bundle, an effect that was also attenuated by
      glutamate. These results suggest that both spontaneous and evoked dopamine
      release in the rat striatum are under the local tonic excitatory influence of
      glutamate. Interactions between central dopamine and glutamate systems that have
      been implicated in the etiologies of Parkinson's disease, schizophrenia, stress,
      and substance abuse. The precise nature of those interactions, however, remains a
      matter of some controversy.

PMID- 11226676
TI  - Nerve growth factor and glial cell line-derived neurotrophic factor restore the
      cholinergic neuronal phenotype in organotypic brain slices of the basal nucleus
      of Meynert.
AB  - Loss of cholinergic neurons is found in the medial septum and nucleus basalis of
      Meynert in Alzheimer's disease. Recent observations suggest that cholinergic
      neurons down-regulate their phenotype and that growth factors may rescue
      cholinergic neurons. The aim of this study was to investigate whether cholinergic
      neurons of the basal nucleus of Meynert can be cultured in rat organotypic
      slices, and if nerve growth factor and glial cell line-derived neurotrophic
      factor can rescue the cholinergic phenotype. In the organotypic slices, glial
      cells, GABAergic and cholinergic neurons were visualized using
      immunohistochemistry. The number of cholinergic neurons was found to be very low
      in slices cultured without exogenous nerve growth factor. Analysis of nerve
      growth factor tissue levels by enzyme-linked immunosorbent assay revealed very
      low endogenous tissue levels. When slices were incubated with 100ng/ml nerve
      growth factor during the initial phase of culturing, a stable expression of
      choline acetyltransferase was found for up to several weeks. After eight weeks in
      culture with nerve growth factor or two to three weeks after nerve growth factor
      withdrawal, numbers of detected cholinergic neurons decreased. Neurons incubated
      with nerve growth factor displayed a significantly enlarged cell soma compared to
      neurons without growth factors. In cultures incubated for up to nine weeks, it
      was also found that glial cell line-derived neurotrophic factor was capable of
      restoring the cholinergic phenotype. The low-affinity p75 and high-affinity trkA
      receptors, as well as the glial cell line-derived neurotrophic factor receptor
      GFRalpha-1, could be visualized in slices using immunohistochemistry. In
      conclusion, it is shown that, in the axotomized organotypic slice model, the
      number of cholinergic neurons is decreased, but can be partly restored by nerve
      growth factor and glial cell line-derived neurotrophic factor.

PMID- 11226677
TI  - Up-regulation of Bcl-xL in response to subtoxic beta-amyloid: role in neuronal
      resistance against apoptotic and oxidative injury.
AB  - Neuron death in Alzheimer's disease is believed to be triggered by an increased
      production of amyloidogenic beta-amyloid peptides, involving both increased
      oxidative stress and activation of a conserved death program. Bcl-xL, an anti
      apoptotic protein of the Bcl-2 family, is expressed at high levels in the adult
      nervous system. Exposure of neuronal cultures to subtoxic concentrations of beta
      amyloid peptide 1-40 (1-10microM) or the fragment 25-35 (1-10microM) up-regulated
      both bcl-xL mRNA and Bcl-xL protein levels, determined by reverse transcriptase
      polymerase chain reaction and western blot analysis. Bcl-xL protein was also up
      regulated during oxidative stress induced by exposure to hydrogen peroxide (3
      100microM) or ferric ions (1-10microM). In contrast, apoptotic stimuli (exposure
      to staurosporine or serum withdrawal) actually decreased neuronal Bcl-xL
      expression. To investigate the role of Bcl-xL in cell death relevant to
      Alzheimer's disease, we stably overexpressed Bcl-xL in human SH-SY5Y
      neuroblastoma cells. Cells overexpressing Bcl-xL were significantly protected
      from beta-amyloid neurotoxicity and staurosporine-induced apoptosis compared to
      vector-transfected controls. In contrast, Bcl-xL overexpression only conferred a
      mild protection against oxidative injury induced by hydrogen peroxide. We
      conclude that up-regulation of Bcl-xL expression in response to subtoxic
      concentrations of beta-amyloid is a stress response that increases the resistance
      of neurons to beta-amyloid neurotoxicity primarily by inhibiting apoptotic
      processes.

PMID- 11226678
TI  - Dopaminergic activity in transgenic mice underexpressing glucocorticoid
      receptors: effect of antidepressants.
AB  - Transgenic mice bearing a transgene coding for a glucocorticoid receptor
      antisense mRNA, which partially blocks glucocorticoid receptor expression, were
      used to investigate the long-term effect of hypothalamic-pituitary-adrenal axis
      dysfunction on brain dopamine transmission. Compared to control mice, the
      transgenic animals showed increased amphetamine-induced locomotor activity and
      increased concentrations of striatal dopamine and its metabolites
      dihydroxyphenylacetic acid and homovanillic acid. Binding of [3H]SCH 23390 and
      [3H]spiperone to, respectively, D1 and D2 dopamine receptors was increased in
      transgenic mice. In contrast, autoradiography of striatal [3H]GBR 12935 binding
      to the dopamine transporter was decreased and the mRNA levels of this
      transporter, measured by in situ hybridization, remained unchanged in the
      substantia nigra pars compacta. The effect of chronic treatment for two weeks
      with amitriptyline or fluoxetine was compared in control and transgenic mice. No
      significant changes were observed in control mice following antidepressant
      treatment, whereas in transgenic mice both antidepressants reduced striatal
      [3H]SCH 23390 and [3H]raclopride specific binding to D1 and D2 receptors.
      Amitriptyline, but not fluoxetine, increased striatal [3H]GBR 12935 binding to
      the dopamine transporter, whereas its mRNA level in the substantia nigra pars
      compacta was decreased in fluoxetine, compared to vehicle- or amitriptyline
      treated transgenic mice. From these results we suggest that hyperactive
      dopaminergic activity of the nigrostriatal pathway controls motor activity in the
      transgenic mice. Furthermore, antidepressant treatment corrected the increased
      striatal D1 and D2 receptors and decreased dopamine transporter levels in the
      transgenic mice.

PMID- 11226679
TI  - Role of cholinergic mossy fibers in medial vestibular and prepositus hypoglossal
      nuclei in vestibular compensation.
AB  - Several lines of evidence have suggested that acetylcholine is a possible
      neurotransmitter/neuromodulator involved in vestibular compensation. Further, the
      central vestibular system, oculo- and spino-motor neurons and peripheral
      vestibular efferents contain abundant cholinergic neurons. However, details of
      cholinergic effective sites during vestibular compensation remain to be
      clarified. In the present study, we selectively damaged rat vestibulo-floccular
      and vestibulo-uvulonodular cholinergic mossy fibers using ethylcholine mustard
      aziridinium ions. In these treated animals, unilateral labyrinthectomy caused
      more severe vestibulo-ocular deficits especially during the initial stage. From
      these findings we suggest that vestibulo-floccular and vestibulo-uvulonodular
      cholinergic mossy fibers contribute to the restoration of a balance between
      intervestibular nuclear activities for the induction of vestibular compensation
      during the initial stage.

PMID- 11226680
TI  - A population of large lamina I projection neurons with selective inhibitory input
      in rat spinal cord.
AB  - Lamina I of the spinal dorsal horn contains a diverse mixture of neurons. Among
      these, a group of giant neurons (Waldeyer cells) has long been recognized. In
      this study we have used immunocytochemistry to characterize a population of
      Waldeyer cells which were identified by the presence of high levels of the
      glycine receptor-associated protein gephyrin on their cell bodies and proximal
      dendrites. Most of these cells (27/29) were retrogradely labelled after injection
      of cholera toxin B subunit into the parabrachial area, and the majority (26/30)
      expressed the protein product of immediate-early gene c-fos, Fos, following
      noxious stimulation. Unlike many lamina I projection neurons, these cells either
      lacked the neurokinin 1 receptor, or expressed it at a very low level. Most of
      the gephyrin puncta on the cells were adjacent to axons that contained glutamate
      decarboxylase (and were therefore presumably GABAergic), which suggests that the
      cells are under powerful inhibitory control. Only around 35% of the puncta were
      associated with axons that expressed the glycine transporter GLYT2 (a marker for
      glycinergic axons); however, the glycine receptor alpha1 subunit was present at
      all of the gephyrin puncta on these cells. The cells received synapses from axons
      that contained nitric oxide synthase, most of which were also GABAergic, and in
      some cases this input was so dense that it outlined the cell bodies and
      dendrites. The innervation by nitric oxide synthase-containing axons was
      selective for these cells, compared to other neurons in the dorsal horn. From the
      results of this study we suggest that the gephyrin-rich cells form a specific
      population of lamina I projection neurons which convey noxious information to the
      brain. These cells are under powerful inhibitory control, and the study provides
      further evidence that inhibitory circuits in the dorsal horn are organized in a
      specific manner.

PMID- 11226681
TI  - Comparison of intracellular calcium signals evoked by heat and capsaicin in
      cultured rat dorsal root ganglion neurons and in a cell line expressing the rat
      vanilloid receptor, VR1.
AB  - The cloning of the receptor for capsaicin, vanilloid receptor 1, has shown it to
      be non-selective cation channel with a high calcium permeability which can be
      opened by noxious heat as well as capsaicin. Here we compare the calcium signals
      produced by native and recombinant capsaicin receptors when activated by either
      heat or capsaicin by imaging intracellular calcium levels ([Ca2+](i)) in rat
      dorsal root ganglion neurons and Chinese hamster ovary cells transfected with the
      rat vanilloid receptor, vanilloid receptor 1. Vanilloid receptor 1 transfected
      cells and a subset of dorsal root ganglion neurons responded to both capsaicin
      and to heating to 50 degrees C with rapid, substantial and reversible rises in
      [Ca2+](i). All except one of the dorsal root ganglion neurons responsive to
      capsaicin also showed sensitivity to heat, and most, but not all, heat-sensitive
      neurons also responded to capsaicin. Both capsaicin and heat responses were
      dependent on the presence of extracellular Ca2+. Non-transfected Chinese hamster
      ovary cells and non-responsive dorsal root ganglion neurons showed only small
      rises in [Ca2+](i) in response to heat which did not depend on the presence of
      external Ca2+. Responsive dorsal root ganglion neurons and vanilloid receptor 1
      transfected cells showed a clear temperature threshold, above which [Ca2+](i)
      increased rapidly. This was estimated to be 42.6+/-0.3 degrees C for vanilloid
      receptor 1 transfected cells and 42.0+/-0.6 degrees C for dorsal root ganglion
      neurons. The competitive capsaicin antagonist capsazepine (10microM) abolished
      [Ca2+](i) increases stimulated by capsaicin in both dorsal root ganglion neurons
      and vanilloid receptor 1 transfected cells. However, responses to heat of a
      similar magnitude in the same cells were inhibited by only 37% by capsazepine
      (10microM). In vanilloid receptor 1 transfected cells, Ruthenium Red (10microM)
      blocked responses to both capsaicin and heat. These results demonstrate that
      imaging of [Ca2+](i) can identify dorsal root ganglion neurons which are
      responsive to both heat and capsaicin. They show that heat and capsaicin
      responses mediated by native and recombinant capsaicin receptors are similar with
      respect to the characteristics and pharmacology examined, suggesting that
      expression of recombinant vanilloid receptor 1 in cell lines accurately
      reproduces the properties of the native receptor.

PMID- 11226682
TI  - Hyper-responsivity in a subset of C-fiber nociceptors in a model of painful
      diabetic neuropathy in the rat.
AB  - While clinical characteristics of diabetic painful neuropathy are well described,
      the underlying electrophysiological basis of the exaggerated painful response to
      stimuli, as well as the presence of spontaneous pain, are poorly understood. In
      order to elucidate peripheral contributions to painful diabetic neuropathy, we
      quantitatively evaluated the function of C-fibers in a rat model of painful
      diabetic neuropathy, diabetes induced by the pancreatic beta-cell toxin
      streptozotocin. While there was no significant effect of diabetes on conduction
      velocity, mechanical threshold or spontaneous activity, the number of action
      potentials in response to sustained threshold and suprathreshold mechanical
      stimuli was significantly increased in the diabetic rats. Moreover, there was a
      clustering of responses of C-fibers in diabetic rats; while two-thirds of C
      fibers fired at the same mean frequency as C-fibers in control rats, one-third of
      C-fibers in diabetic rats were markedly hyper-responsive, demonstrating a
      threefold increase in firing frequency. The high-firing-frequency C-fibers in
      rats with diabetes also had faster conduction velocity than the low-firing
      frequency C-fibers in rats with diabetes or in C-fibers in control rats. The
      hyper-responsiveness was characterized by a selective increase of the shortest
      interspike intervals (<100ms) in the burst component (first 10s) of the response
      to a sustained suprathreshold stimulus; in the plateau phase (last 50s) of the
      response to a 60-s suprathreshold stimulus, we found a selective increase of
      interspike intervals between 100 and 300ms in hyper-responsive C-fibers in rats
      with diabetes. The hyper-responsiveness did not correlate with mechanical
      threshold, presence of spontaneous activity or location of the fiber's receptive
      field. In summary, in an established model of painful diabetic neuropathy in the
      rat, a subset of C-fibers demonstrated a marked hyper-responsiveness to
      mechanical stimuli. The subset was also found to have a greater mean conduction
      velocity than the fibers not demonstrating this hyper-responsivity. The present
      findings suggest that study of individual neurons in vitro may allow elucidation
      of the ionic basis of enhanced nociception in diabetic neuropathy.

PMID- 11226683
TI  - Temporal and spatial variations in slow axonal transport velocity along
      peripheral motoneuron axons.
AB  - Neuronal axons are cellular extensions that can reach more than a meter in
      length. To maintain such a structure, macromolecules synthesized in cell bodies
      must be transported to the distal axons. Proteins associated with membranous
      organelles are generally transported in several fast transported groups, while
      cytoplasmic proteins, mostly composed of cytoskeletal proteins, are transported
      in slowly transported groups. Neurofilaments are a main component in the slowly
      transported group. Composed of three polypeptide subunits (NF-H, NF-M and NF-L),
      they are the most abundant cytoskeletal element in large myelinated axons. In
      various neurological or neurotoxic disorders, selective accumulation of
      neurofilaments was observed in different compartments of a neuron (cell bodies,
      proximal or distal axons). The underlying mechanism for this regional selectivity
      has been unclear. Using the classical pulse labeling method, we examined the
      changes in neurofilament transport velocity in transgenic mice that overexpress
      different neurofilament subunits. We present evidence that at least three
      velocities of neurofilament transport exist along peripheral motor axons. Each of
      these velocities was altered differently depending on which neurofilament subunit
      was overexpressed. We suggest that neurofilament transport in motor axons
      consists of multiple successive stages and that each of these stages is carried
      out by different transport mechanisms. These differences provide a basis for the
      regional deficiencies in axonal transport associated with several neurological
      disorders.

PMID- 11226684
TI  - Regional expression of the histamine H(2) receptor in adult and developing rat
      brain.
AB  - Histamine H(2) receptor expression was studied in adult and developing rat brain.
      Northern blot and in situ hybridizations indicated that histamine H(2) receptor
      messenger RNA expression is widespread and not limited to neurons in the adult
      rat brain. Prominent H(2) receptor expression in the adult brain was seen in the
      dentate gyrus, hippocampal subfields CA1-CA3, piriform cortex and in some
      diencephalic nuclei, e.g. in the suprachiasmatic nucleus and the red nucleus.
      Most of the adult brain nuclei displayed a very low H(2) receptor expression.
      Histamine H(2) receptor was also expressed during development in widespread areas
      of the central nervous system, coinciding with the transient production of
      histamine in the raphe neurons at embryonic day 15. From embryonic days 16 and 17
      until birth, histamine H(2) receptor expression in the cortical plate coincided
      with the development and sprouting of histaminergic fibers into the cerebral
      cortex. The widespread and diffuse expression of histamine H(2) receptors in the
      adult rat brain suggests that the H(2) receptor modulates the excitability of
      neuron and astrocyte functions in many brain areas rather than mediating targeted
      cell-to-cell signals. During development, histamine H(2) receptor expression is
      seen in several target areas for the histaminergic fibers. This could indicate
      that histamine, through the H(2) receptor, regulates fetal development of the
      brain.

PMID- 11226685
TI  - Distribution of the messenger RNA for the small conductance calcium-activated
      potassium channel SK3 in the adult rat brain and correlation with
      immunoreactivity.
AB  - Small conductance calcium-activated potassium channels are voltage independent
      potassium channels which modulate the firing patterns of neurons by activating
      the slow component of the afterhyperpolarization. The genes encoding a family of
      small conductance calcium-activated potassium channels have been cloned and up to
      now three known members have been described and named small conductance calcium
      activated potassium channel type 1, small conductance calcium-activated potassium
      channel type 2 and small conductance calcium-activated potassium channel type 3;
      the distribution of their messenger RNA in the rat CNS has already been performed
      but only in a limited detail. The present study represents the first detailed
      analysis of small conductance calcium-activated potassium channel type 3 mRNA
      distribution in the adult rat brain and resulted in a strong to moderate
      expression of signal in medial habenular nucleus, substantia nigra compact part,
      suprachiasmatic nucleus, ventral tegmental area, lateral septum, dorsal raphe and
      locus coeruleus. Immunohistological experiments were also performed and confirmed
      the presence of small conductance calcium-activated potassium channel type 3
      protein in medial habenular nucleus, locus coeruleus and dorsal raphe. Given the
      importance of dorsal raphe, locus coeruleus and substantia nigra/ventral
      tegmental area for serotonergic, noradrenergic and dopaminergic transmission
      respectively, our results pose the morphological basis for further studies on the
      action of small conductance calcium-activated potassium channel type 3 in
      serotonergic, noradrenergic and dopaminergic transmission.

PMID- 11226686
TI  - Sodium-hydrogen exchangers and sodium-bicarbonate co-transporters: ontogeny of
      protein expression in the rat brain.
AB  - We used western blotting to examine the developmental profiles (at embryonic day
      16 and postnatal days 1, 13, 23, 33 and 105) of protein expression for three
      sodium-hydrogen exchanger isoforms (1, 2 and 4) and for a sodium-bicarbonate co
      transporter in three CNS regions (cortex, cerebellum and brainstem-diencephalon).
      In microsomal preparations, sodium-hydrogen exchanger isoform 1 and sodium
      bicarbonate co-transporter protein expression in the CNS increases gradually from
      embryonic day 16 (25-40% of the adult level) to postnatal day 105. In contrast,
      sodium-hydrogen exchanger isoform 2 and 4 expression reaches a maximum (three to
      20 times the adult level) at around three to four weeks of age. There is
      significant regional heterogeneity in the expression of sodium-hydrogen exchanger
      and sodium-bicarbonate co-transporter proteins in the rat CNS. Sodium-hydrogen
      exchanger isoform 1 was highly expressed in the brainstem-diencephalon, whereas
      the sodium-bicarbonate co-transporter was robustly expressed in the cerebellum
      and brainstem-diencephalon. These data indicate that the expression of sodium
      hydrogen exchanger and sodium-bicarbonate co-transporter proteins varies as a
      function of both development and specific brain region.

PMID- 11226687
TI  - Contribution of presynaptic calcium-activated potassium currents to transmitter
      release regulation in cultured Xenopus nerve-muscle synapses.
AB  - Using Xenopus nerve-muscle co-cultures, we have examined the contribution of
      calcium-activated potassium (K(Ca)) channels to the regulation of transmitter
      release evoked by single action potentials. The presynaptic varicosities that
      form on muscle cells in these cultures were studied directly using patch-clamp
      recording techniques. In these developing synapses, blockade of K(Ca) channels
      with iberiotoxin or charybdotoxin decreased transmitter release by an average of
      35%. This effect would be expected to be caused by changes in the late phases of
      action potential repolarization. We hypothesize that these changes are due to a
      reduction in the driving force for calcium that is normally enhanced by the local
      hyperpolarization at the active zone caused by potassium current through the
      K(Ca) channels that co-localize with calcium channels. In support of this
      hypothesis, we have shown that when action potential waveforms were used as
      voltage-clamp commands to elicit calcium current in varicosities, peak calcium
      current was reduced only when these waveforms were broadened beginning when
      action potential repolarization was 20% complete. In contrast to peak calcium
      current, total calcium influx was consistently increased following action
      potential broadening. A model, based on previously reported properties of ion
      channels, faithfully reproduced predicted effects on action potential
      repolarization and calcium currents. From these data, we suggest that the large
      conductance K(Ca) channels expressed at presynaptic varicosities regulate
      transmitter release magnitude during single action potentials by altering the
      rate of action potential repolarization, and thus the magnitude of peak calcium
      current.

PMID- 11226688
TI  - Evidence from the waking electroencephalogram that short sleepers live under
      higher homeostatic sleep pressure than long sleepers.
AB  - We used the waking electroencephalogram to study the homeostatic sleep regulatory
      process in human short sleepers and long sleepers. After sleeping according to
      their habitual schedule, nine short sleepers (sleep duration < 6 h) and eight
      long sleepers (> 9 h) were recorded half-hourly during approximately 40 h of
      wakefulness in a constant routine protocol. Within the frequency range of 0.25
      20.0 Hz, spectral power density in the 5.25-9.0 and 17.25-18.0 Hz ranges was
      higher in short sleepers than in long sleepers. In both groups, increasing time
      awake was associated with an increase of theta/low-frequency alpha activity (5.25
      9.0 Hz), whose kinetics followed a saturating exponential function. The time
      constant did not differ between groups and was similar to the previously obtained
      time constant of the wake-dependent increase of slow-wave activity (0.75-4.5 Hz)
      in the sleep electroencephalogram. In addition, the time constant of the decrease
      of slow-wave activity during extended recovery sleep following the constant
      routine did not differ between groups. However, short sleepers showed an abiding
      enhancement of theta/low-frequency alpha activity during wakefulness after
      recovery sleep that was independent of the homeostatic process. It is concluded
      that, while the kinetics of the homeostatic process do not differ between the two
      groups, short sleepers live under and tolerate higher homeostatic sleep pressure
      than long sleepers. The homeostat-independent enhancement of theta/low-frequency
      alpha activity in the waking electroencephalogram in the short sleepers may be
      genetically determined or be the result of long-term adaptation to chronically
      short sleep.

PMID- 11226689
TI  - Role of excitatory amino acid transporter 1 in neonatal rat neuronal damage
      induced by hypoxia-ischemia.
AB  - The role of excitatory amino acid transporter 1 in neonatal rat neuronal damage
      was studied following hypoxia-ischemia. To induce hypoxia-ischemia injury, rats
      on postnatal day 7 were exposed to 8 % oxygen for 2 h following unilateral common
      carotid artery ligation. According to brain damage scoring based on Cresyl Violet
      staining, the neuronal damage time-dependently changed in the ischemic regions
      following hypoxia-ischemia. Immunohistochemical studies showed that excitatory
      amino acid transporter 1 expression was mainly observed in the cerebral cortex
      ipsilateral to common carotid artery ligation and markedly increased at 24 h and
      48 h following hypoxia-ischemia. Combined with confocal laser scanning
      microscopic analysis, double staining showed that excitatory amino acid
      transporter 1 positive staining appeared in neurons as well as astrocytes after
      hypoxia-ischemia. Most excitatory amino acid transporter 1 positive staining
      cells exhibited regular morphological characteristics and only a few were double
      stained by terminal deoxynucleotidyl transferase-mediated
      deoxyuridinetriphosphate nick-end labeling. Down-regulation of excitatory amino
      acid transporter 1 expression by intraventricular administration of specific
      antisense oligonucleotide exacerbated neuronal damage in hypoxia-ischemia brain.
      These results suggest that the increase of excitatory amino acid transporter 1
      expression may be involved in a pathophysiological process of hypoxia-ischemia
      brain damage and may reflect a self-compensative mechanism for protecting neurons
      from further injury.

PMID- 11226690
TI  - Perforant path lesion induces up-regulation of stathmin messenger RNA, but not
      SCG10 messenger RNA, in the adult rat hippocampus.
AB  - In this study, we performed in situ hybridization analysis of the expression
      pattern of two growth-associated proteins, stathmin and SCG10, in the hippocampus
      after unilateral lesion of the perforant pathway, the main excitatory input from
      the entorhinal cortex to the hippocampus. Stathmin is one of the major neural
      enriched cytosolic phosphoproteins and a potential target of cyclic-AMP-dependent
      kinases [Jin L. W. et al. (1996) Neurobiol. Aging 17, 331-341; Leighton I. A. et
      al. (1993) Molec. Cell Biochem. 127/128, 151-156]. Three days after the lesion,
      stathmin messenger RNA was up-regulated ipsilaterally in the hilus, in the
      granule cell layer of the dentate gyrus and in the pyramidal cell layer of the
      CA1 region. Simultaneously, the hilar region of the contralateral dentate gyrus
      showed an increased stathmin messenger RNA expression. This altered expression
      pattern was observed until 15 days after lesion. Stathmin messenger RNA
      expression returned to a normal level until 21 days after lesion in all regions
      analysed. SCG10, a membrane-bound neuronal growth-associated protein belonging to
      the SCG10/stathmin gene family, did not show any alteration of messenger RNA
      expression after perforant path lesion. The temporal changes of stathmin
      messenger RNA expression in the ipsilateral hippocampus correspond well to the
      process of reactive synaptogenesis. The enhanced messenger RNA expression in the
      hilar region of the contralateral dentate gyrus might suggest a role in neurite
      elongation, since this region is the origin of commissural fibres involved in the
      sprouting response in the deafferented hippocampus. The present study provides
      evidence that the induction of specific growth-associated proteins is
      differentially regulated in the hippocampus.

PMID- 11226691
TI  - Total number and distribution of inhibitory and excitatory synapses on
      hippocampal CA1 pyramidal cells.
AB  - The integrative properties of neurons depend strongly on the number, proportions
      and distribution of excitatory and inhibitory synaptic inputs they receive. In
      this study the three-dimensional geometry of dendritic trees and the density of
      symmetrical and asymmetrical synapses on different cellular compartments of rat
      hippocampal CA1 area pyramidal cells was measured to calculate the total number
      and distribution of excitatory and inhibitory inputs on a single cell.A single
      pyramidal cell has approximately 12,000 microm dendrites and receives around
      30,000 excitatory and 1700 inhibitory inputs, of which 40 % are concentrated in
      the perisomatic region and 20 % on dendrites in the stratum lacunosum-moleculare.
      The pre- and post-synaptic features suggest that CA1 pyramidal cell dendrites are
      heterogeneous. Strata radiatum and oriens dendrites are similar and differ from
      stratum lacunosum-moleculare dendrites. Proximal apical and basal strata radiatum
      and oriens dendrites are spine-free or sparsely spiny. Distal strata radiatum and
      oriens dendrites (forming 68.5 % of the pyramidal cells' dendritic tree) are
      densely spiny; their excitatory inputs terminate exclusively on dendritic spines,
      while inhibitory inputs target only dendritic shafts. The proportion of
      inhibitory inputs on distal spiny strata radiatum and oriens dendrites is low (
      approximately 3 %). In contrast, proximal dendritic segments receive mostly (70
      100 %) inhibitory inputs. Only inhibitory inputs innervate the somata (77-103 per
      cell) and axon initial segments. Dendrites in the stratum lacunosum-moleculare
      possess moderate to small amounts of spines. Excitatory synapses on stratum
      lacunosum-moleculare dendrites are larger than the synapses in other layers, are
      frequently perforated ( approximately 40 %) and can be located on dendritic
      shafts. Inhibitory inputs, whose percentage is relatively high ( approximately 14
      17 %), also terminate on dendritic spines. Our results indicate that: (i) the
      highly convergent excitation arriving onto the distal dendrites of pyramidal
      cells is primarily controlled by proximally located inhibition; (ii) the
      organization of excitatory and inhibitory inputs in layers receiving Schaffer
      collateral input (radiatum/oriens) versus perforant path input (lacunosum
      moleculare) is significantly different.

PMID- 11226692
TI  - Nociceptin/orphanin FQ regulates neuroendocrine function of the limbic
      hypothalamic-pituitary-adrenal axis.
AB  - We examined the effects of the neuropeptide nociceptin/orphanin FQ on activity of
      the limbic-hypothalamic-pituitary-adrenal axis (also known as the stress axis) in
      rats. This axis regulates important metabolic functions, and initiates critical
      neuroendocrine responses that cope with environmental threats and challenges to
      homeostatic functioning. Disregulation of the limbic-hypothalamic-pituitary
      adrenal axis is associated with impaired physical and psychological health. In
      the present experiments, rats were treated with intracerebroventricular
      injections of nociceptin/orphanin FQ in the presence or absence of acute
      stressors. Plasma adrenocorticotrophic hormone and corticosterone concentrations
      were assayed 15 or 30min after injections. In the rats that were not exposed to
      stress, nociceptin/orphanin FQ produced dose-orderly elevations of circulating
      adrenocorticotrophic hormone and corticosterone concentrations. These effects
      were also found after administration of the nociceptin/orphanin FQ analogues, des
      Phe orphanin FQ and [Phe(1)psi(CH(2)-NH)Gly(2)]nociceptin((1-13))NH(2). In rats
      that were exposed to the mild stress of a novel environment, nociceptin/orphanin
      FQ administration enhanced the stress-induced elevations of plasma
      adrenocorticotrophic hormone concentrations and prolonged the stress-induced
      elevations of plasma corticosterone concentrations. In rats that were exposed to
      restraint stress, nociceptin/orphanin FQ administration did not augment the
      stress-induced elevations in plasma hormones, perhaps because of a ceiling
      effect. We conclude that administration of nociceptin/orphanin FQ activates
      neuroendocrine activity of the limbic-hypothalamic-pituitary-adrenal axis even in
      the absence of a stressor, and may delay the shutdown of these physiological
      responses after exposure to acute mild stress. In light of the known functions of
      this axis, it appears that nociceptin/orphanin FQ participates in the regulation
      of important metabolic functions, and may be implicated in physiological
      responses to stress. This interaction between nociceptin/orphanin FQ and the
      limbic-hypothalamic-pituitary-adrenal axis implicates nociceptin/orphanin FQ in
      important aspects of physiological and psychological well-being.

PMID- 11226694
TI  - Impulse activity of ventral tegmental area neurons during heroin self
      administration in rats.
AB  - To assess the pattern of mesocorticolimbic dopamine activity associated with drug
      seeking and drug-taking behavior, we recorded impulse activity of ventral
      tegmental area neurons during intravenous heroin self-administration in trained
      rats. Although these neurons had considerable variability, two major groups-units
      with triphasic long-duration spikes and biphasic short-duration spikes-were
      identified. Relative to a slow and irregular basal activity of long-spike units,
      the first self-administration of each session was preceded by a phasic neuronal
      activation and followed by a more sustained drug-induced activation that reached
      a maximum at the time of the second self-injection. After each subsequent heroin
      self-injection, the discharge rate transiently decreased, correlating with the
      blockade of preceding motor activation and the appearance of freezing, but slowly
      and gradually increased again in parallel with searching behavior, reaching a
      maximum at the time of the next self-injection. Passive drug injections in either
      drug-naive, freely moving or drug-experienced, anesthetized rats caused much
      smaller, tonic increases in activity of long-spike units; these monophasic
      increases changed into biphasic responses with repeated injections. Although
      short-spike units had highly varying discharge rate and showed phasic activation
      during movement, during heroin self-injections they generally mimicked the
      activity pattern seen in long-spike units. Our results indicate that in behaving
      animals indirect "identification" of dopamine cells based on their distinctive
      electrophysiological features is more complex than in vitro and in anesthetized
      preparations. With respect to long-spike units, a candidate group of presumed
      dopamine neurons, our data agree with the view that mesocorticolimbic dopamine
      activation is important for the activational and/or motivational aspects of
      heroin-taking behavior and suggest the role of an abrupt termination of dopamine
      activation for drug reinforcement (reward). Although the neurochemical nature of
      long- and short-spike units is obviously different, similar changes in their
      activity may indicate that they are regulated by similar afferent inputs and that
      these inputs change similarly during drug-taking behavior.

PMID- 11226693
TI  - Synergistic neurotoxicity of opioids and human immunodeficiency virus-1 Tat
      protein in striatal neurons in vitro.
AB  - Human immunodeficiency virus (HIV) infection selectively targets the striatum, a
      region rich in opioid receptor-expressing neural cells, resulting in gliosis and
      neuronal losses. Opioids can be neuroprotective or can promote neurodegeneration.
      To determine whether opioids modify the response of neurons to human
      immunodeficiency virus type 1 (HIV-1) Tat protein-induced neurotoxicity, neural
      cell cultures from mouse striatum were initially characterized for mu and/or
      kappa opioid receptor immunoreactivity. These cultures were continuously treated
      with morphine, the opioid antagonist naloxone, and/or HIV-1 Tat (1-72) protein, a
      non-neurotoxic HIV-1 Tat deletion mutant (TatDelta31-61) protein, or
      immunoneutralized HIV-1 Tat (1-72) protein. Neuronal and astrocyte viability was
      examined by ethidium monoazide exclusion, and by apoptotic changes in nuclear
      heterochromatin using Hoechst 33342. Morphine (10nM, 100nM or 1microM)
      significantly increased Tat-induced (100 or 200nM) neuronal losses by about two
      fold at 24h following exposure. The synergistic effects of morphine and Tat were
      prevented by naloxone (3microM), indicating the involvement of opioid receptors.
      Furthermore, morphine was not toxic when combined with mutant Tat or
      immunoneutralized Tat. Neuronal losses were accompanied by chromatin condensation
      and pyknosis. Astrocyte viability was unaffected. These findings demonstrate that
      acute opioid exposure can exacerbate the neurodegenerative effect of HIV-1 Tat
      protein in striatal neurons, and infer a means by which opioids may hasten the
      progression of HIV-associated dementia.

PMID- 11226695
TI  - No functional effects of embryonic neuronal grafts on motor deficits in a 3
      nitropropionic acid rat model of advanced striatonigral degeneration (multiple
      system atrophy).
AB  - Intrastriatal injection of 3-nitropropionic acid results in secondary excitotoxic
      local damage and retrograde neuronal cell loss in substantia nigra pars compacta,
      thus mimicking salient features of striatonigral degeneration, the core pathology
      underlying Parkinsonism associated with multiple system atrophy. We used 3
      nitropropionic acid to create a rat model of advanced striatonigral degeneration
      in order to assess the effects of embryonic allografts upon rotational and
      complex-motor behavioural abnormalities. Following stereotaxic intrastriatal
      administration of 500nmol 3-nitropropionic acid in male Wistar rats we observed
      consistent amphetamine- and apomorphine-induced ipsiversive rotation.
      Furthermore, there were marked deficits of contralateral paw reaching.
      Subsequently, animals received intrastriatal implantations of either E14
      mesencephalic or striatal or mixed embryonic cell suspensions. In addition, one
      group received sham injections. Grafted rats were followed for up to 21 weeks and
      repeated behavioural tests were obtained during this period. Drug-induced
      rotation asymmetries and complex motor deficits measured by paw reaching tests
      were not compensated by embryonic grafts. Persistence of drug-induced rotations
      and of paw reaching deficits following transplantation probably reflects severe
      atrophy of adult striatum, additional nigral degeneration as well as glial
      demarcation of embryonic grafts. We suggest that dopamine rich embryonic grafts
      fail to induce functional recovery in a novel 3-nitropropionic acid rat model of
      advanced striatonigral degeneration (multiple system atrophy).

PMID- 11226696
TI  - Co-transmitter function of ATP in central catecholaminergic neurons of the rat.
AB  - Intracellular recordings were made in a mid-pontine slice preparation of the rat
      brain containing the nucleus locus coeruleus. Focal electrical stimulation evoked
      biphasic synaptic potentials consisting of early depolarizing (d.p.s.p.) and late
      hyperpolarizing (i.p.s.p.) components. The alpha(2)-adrenoceptor antagonist
      idazoxan inhibited the i.p.s.p. without altering the d.p.s.p. All of the
      following experiments were carried out in the presence of kynurenic acid and
      picrotoxin to block the glutamatergic and GABAergic fractions of the d.p.s.p.,
      respectively. Guanethidine, which is known to inhibit noradrenaline and ATP
      release from nerve terminals of postganglionic sympathetic nerves, depressed both
      the d.p.s.p. and the i.p.s.p. in a concentration-dependent manner. Damage of
      catecholaminergic nerve terminals by 6-hydroxydopamine also decreased both the
      d.p.s.p. and the i.p.s.p. The P2 receptor antagonist pyridoxal-phosphate-6
      azophenyl-2',4'-disulphonic acid (PPADS) depressed the d.p.s.p., whereas the
      i.p.s.p. remained unaffected. The further application of PPADS did not increase
      the depression of the d.p.s.p. by guanethidine. Superfusion with the mixed alpha
      adrenoceptor agonist noradrenaline or the selective P2 receptor agonist adenosine
      5'-O-(2-thiodiphosphate) inhibited both the d.p.s.p. and the i.p.s.p. The
      inhibitory effects of these agonists were prevented by the respective antagonists
      idazoxan or suramin. In the presence of suramin noradrenaline failed to inhibit
      the residual d.p.s.p. Superfused noradrenaline potentiated rather than inhibited
      responses to pressure-applied alpha,beta-methylene-ATP; superfused adenosine 5'-O
      (2-thiodiphosphate) did not interact with pressure-applied noradrenaline. In
      conclusion, we present electrophysiological evidence for the co-release of ATP
      and catecholamines in the CNS. At the cell somata of neurons in the locus
      coeruleus, noradrenaline and ATP activate inhibitory alpha(2)-adrenoceptors and
      excitatory P2 receptors, respectively. In addition, inhibitory presynaptic
      autoreceptors of the alpha(2) and P2 types appear to regulate release of the two
      co-transmitters.

PMID- 11226697
TI  - Induction of heat shock proteins and motor function deficits after focal
      cerebellar injury.
AB  - A weight drop model of focal cerebellar injury was used to identify heat shock
      protein induction and motor function deficits in the anesthetized, adult male,
      Sprague-Dawley rat. All animals were trained on a beam walking test prior to
      surgery. Groups of animals received severe, mild or sham weight drop injury to
      the lateral/paravermal region of the cerebellum. The mild and sham-injured
      animals showed no motor deficits in the beam walking test, whereas animals with
      severe cerebellar injury showed significant motor deficits in the beam walking
      test that approached recovery of motor function 20 days after injury. Following
      severe injury, induction of heat shock protein of 27kDa was observed in Purkinje
      cells and in neurons of the deep cerebellar nuclei, as well as Bergmann glial
      cells, glial cells located in the granule cell layer and the underlying white
      matter. Following mild injury, heat shock protein of 27kDa induction was observed
      in Purkinje cells and glial cells, but not in neurons of the deep cerebellar
      nuclei. The labeled Purkinje cells were widely distributed in the ipsilateral
      cerebellar cortex. Many of the glial cells that were immunostained with heat
      shock protein of 27kDa co-localized with cells immunoreactive for glial
      fibrillary acidic protein. After severe injury, heat shock protein of 72kDa was
      localized mainly in granule cells at the site of the trauma and in the
      ipsilateral deep cerebellar nuclei whereas, after mild injury, light labeling was
      observed only in the granule cell layer. The results demonstrate that focal
      cerebellar injury has profound effects on motor behavior and induces different
      families of heat shock proteins in specific groups of neurons and glial cells in
      the cerebellum.

PMID- 11226698
TI  - Motor skills and motor learning in Lurcher mutant mice during aging.
AB  - Motor learning abilities on the rotorod and motor skills (muscular strength,
      motor coordination, static and dynamic equilibrium) were investigated in three-,
      nine-, 15- and 21-month-old Lurcher and control mice. Animals were subjected to
      motor training on the rotorod before being subjected to motor skills tests. The
      results showed that control mice exhibited decrease of muscular strength and
      specific equilibrium impairments in static conditions with age, but were still
      able to learn the motor task on the rotorod even in old age. These results
      suggest that, in control mice, efficiency of the reactive mechanisms, which are
      sustained by the lower transcerebellar loop (cerebello-rubro-olivo-cerebellar
      loop), decreased with age, while the efficiency of the proactive adjustments,
      which are sustained by the upper transcerebellar loop (cerebello-thalamo-cortico
      ponto-cerebellar loop), did not. In spite of their motor deficits, Lurcher
      mutants were able to learn the motor task at three months, but exhibited severe
      motor learning deficits as soon as nine months. Such a deficit seems to be
      associated with dynamic equilibrium impairments, which also appeared at nine
      months in these mutants. By two months of age, degeneration of the cerebellar
      cortex and the olivocerebellar pathway in Lurcher mice has disrupted both lower
      and upper transcerebellar loops. Disruption of the lower loop could well explain
      precocious static equilibrium deficits. However, in spite of disruption of the
      upper loop, motor learning and dynamic equilibrium were preserved in young mutant
      mice, suggesting that either deep cerebellar nuclei and/or other motor structures
      involved in proactive mechanisms needed to maintain dynamic equilibrium and to
      learn motor tasks, such as the striatopallidal system, are sufficient. The fact
      that, in Lurcher mutant mice, motor learning decreased by the age of nine months
      suggests that the above-mentioned structures are less efficient, likely due to
      degeneration resulting from precocious and focused neurodegeneration of the
      cerebellar cortex. From this behavioral approach of motor skills and motor
      learning during aging in Lurcher mutant mice, we postulated the differential
      involvement of two transcerebellar systems in equilibrium maintenance and motor
      learning. Moreover, in these mutants, we showed that motor learning abilities
      decreased with age, suggesting that the precocious degeneration of the cerebellar
      Purkinje cells had long-term effects on motor structures which are not primarily
      affected. Thus, from these results, Lurcher mutant mice therefore appear to be a
      good model to study the pathological evolution of progressive neurodegeneration
      in the central nervous system during aging.

PMID- 11226699
TI  - Expression of GABA(A) receptor subunits in rat brainstem auditory pathways:
      cochlear nuclei, superior olivary complex and nucleus of the lateral lemniscus.
AB  - Inhibition by GABA is important for auditory processing, but any adaptations of
      the ionotropic type A receptors are unknown. Here we describe, using in situ
      hybridization, the subunit expression patterns of GABA(A) receptors in the rat
      cochlear nucleus, superior olivary complex, and dorsal and ventral nuclei of the
      lateral lemniscus. All neurons express the beta3 and gamma2L subunit messenger
      RNAs, but use different alpha subunits. In the dorsal cochlear nucleus, fusiform
      (pyramidal) and giant cells express alpha1, alpha3, beta3 and gamma2L. Dorsal
      cochlear nucleus interneurons, particularly vertical or tuberculoventral cells
      and cartwheel cells, express alpha3, beta3 and gamma2L. In the ventral cochlear
      nucleus, octopus cells express alpha1, beta3, gamma2L and delta. Spherical cells
      express alpha1, alpha3, alpha5, beta3 and gamma2L. In the superior olivary
      complex, the expression profile is alpha3, alpha5, beta3 and gamma2L. Both dorsal
      and ventral cochlear nucleus granule cells express alpha1, alpha6, beta3 and
      gamma2L; unlike their cerebellar granule cell counterparts, they do not express
      beta2, gamma2S or the delta subunit genes. The delta subunit's absence from
      cochlear nucleus granule cells may mean that tonic inhibition mediated by
      extrasynaptic GABA(A) receptors is less important for this cell type. In both the
      dorsal and ventral nuclei of the lateral lemniscus, alpha1, beta3 and gamma2L are
      the main subunit messenger RNAs; the ventral nucleus also expresses the delta
      subunit. We have mapped, using in situ hybridization, the subunit expression
      patterns of the GABA(A) receptor in the auditory brainstem nuclei. In contrast to
      many brain regions, the beta2 subunit gene and gamma2S splice forms are not
      highly expressed in auditory brainstem nuclei. GABA(A) receptors containing beta3
      and gamma2L may be particularly well suited to auditory processing, possibly
      because of the unique phosphorylation profile of this subunit combination.

PMID- 11226700
TI  - Hypothermia prevents hearing loss and progressive hair cell loss after transient
      cochlear ischemia in gerbils.
AB  - The effects of hypothermia on ischemia-reperfusion injury of the cochlea were
      studied in gerbils. Hearing was assessed by sequentially recording compound
      action potentials before, during and after the ischemia. The degree of hair cell
      loss in the organ of Corti was evaluated in specimens stained with rhodamine
      phalloidin and the dye Hoechst 33342. Ischemic insult was applied to the animals
      by occluding the bilateral vertebral arteries for 15 min under normothermic or
      hypothermic (rectal temperature 32 degrees C) conditions. Interruption of the
      blood supply to the cochlea caused a tremendous increase in the compound action
      potential threshold, which usually recovered to some extent with reperfusion. In
      the ischemia/normothermic group, the threshold did not return to the pre-ischemic
      level. The average increase in the threshold seven days after ischemia was 20.0
      dB. Histologically, the hair cell loss increased gradually until four days after
      the ischemic insult. On the seventh day, the mean loss of inner and outer hair
      cells at the basal turn was 31.1 % and 2.4 %, respectively. In the
      ischemia/hypothermic group, the threshold returned to the pre-ischemic level
      within 30 min after reperfusion and remained stable thereafter. The mean loss of
      inner and outer hair cells on the seventh day was 0.1 % and 0.2 %, respectively.
      These results indicate that hypothermia can prevent inner ear damage, which
      otherwise occurs after transient ischemia of the cochlea.

PMID- 11226701
TI  - Evidence that regenerating optic axons maintain long-term growth in the lizard
      Ctenophorus ornatus: growth-associated protein-43 and gefiltin expression.
AB  - In the lizard, Ctenophorus ornatus, the optic nerve regenerates but animals
      remain blind via the experimental eye, presumably as a result of axons failing to
      consolidate a retinotopic map in the optic tectum. Here we have examined
      immunohistochemically the expression of the growth-associated protein GAP-43 and
      the low-molecular-weight intermediate filament protein gefiltin, up to one year
      after optic nerve crush. Both proteins were found to be permanently up-regulated,
      suggesting that regenerating axons are held in a permanent state of re-growth. We
      speculate that, in the lizard, the continued expression of GAP-43 and the failure
      to switch from the expression of low- to high-molecular-weight intermediate
      filament proteins are associated with the inability to consolidate a retinotopic
      projection.

PMID- 11226702
TI  - Changes in neuropeptide expression in the trigeminal ganglion following inferior
      alveolar nerve section in the ferret.
AB  - Changes in neuropeptide expression in afferent nerve fibres may play a role in
      the persistent sensory abnormalities that can be experienced following trigeminal
      nerve injuries. We have therefore studied changes in the expression of the
      neuropeptides substance P, calcitonin gene-related peptide, enkephalin, galanin,
      neuropeptide Y and vasoactive intestinal polypeptide in the trigeminal ganglion
      following peripheral nerve injury. In anaesthetised adult female ferrets, the
      left inferior alveolar nerve was sectioned and recovery allowed for three days,
      three weeks or 12 weeks prior to perfusion-fixation. During a second procedure,
      one week prior to perfusion, the inferior alveolar nerve was exposed and an
      injection made central to the injury site using a mixture of 4 % Fluorogold and 4
      % isolectin B4 conjugated to horseradish peroxidase to identify cell bodies with
      axons in the inferior alveolar nerve and cells with unmyelinated axons within
      this population, respectively. Control animals received tracer injection alone.
      After harvesting the tissue, sagittal sections were taken from both the right and
      left ganglia and immunohistochemical staining was used to reveal the presence of
      peptides and isolectin B4-horseradish peroxidase tracer. Within the Fluorogold
      labelled population, cell counts revealed a significant reduction in the
      proportion of substance P-containing cells at three days (P = 0.0025), three
      weeks (P = 0.0094) and three months (P = 0.0149) after nerve section, and a
      significant reduction in the proportion of calcitonin gene-related peptide
      containing cells at three days (P = 0.0003) and three weeks (P = 0.007). No
      significant changes were seen in the expression of the other peptides, or at
      other time periods. A significant reduction in the number of isolectin B4
      horseradish peroxidase-positive cells (with unmyelinated axons) was seen at three
      days (P = 0.0025), three weeks (P = 0.0074) and three months after the injury (P
      = 0.0133). These results demonstrate a significant reduction in the expression of
      some neuropeptides in the early stages after inferior alveolar nerve section.
      Some of the results differ markedly from those reported previously in other
      systems, and may be related to the specific nerve studied, species variations or
      differences between spinal and trigeminal nerves.

PMID- 11226703
TI  - Increased conduction velocity of nociceptive primary afferent neurons during
      unilateral hindlimb inflammation in the anaesthetised guinea-pig.
AB  - Decreases in durations of action potentials (C- and Adelta-fibre units) and
      afterhyperpolarisations (A-fibre units) occur in somata of nociceptive dorsal
      root ganglion neurons during hindlimb inflammation induced in young guinea-pigs
      by intradermal injections of Complete Freund's Adjuvant into the ipsilateral leg
      and foot. Here we present evidence that the single-point conduction velocity
      (i.e. estimated over a single conduction distance) of these nociceptive neurons
      is increased during this type of inflammation. The single-point conduction
      velocities in anaesthetised untreated guinea-pigs (control) were compared with
      those two and four days after Complete Freund's Adjuvant treatment in two types
      of experiment. The first involved intracellular voltage recordings from somata of
      ipsilateral L6 and S1 dorsal root ganglion neurons. Units were classified as C,
      Adelta or Aalpha/beta on the basis of their dorsal root conduction velocities and
      characterised as nociceptive, low-threshold mechanoreceptive or unresponsive
      according to their responses to mechanical and thermal stimuli. Compared with
      untreated animals, significant increases of 54% for C-fibre nociceptive units and
      46% for A-fibre nociceptive units in the medians of dorsal root single-point
      conduction velocities were found four days after Complete Freund's Adjuvant
      treatment. These increases were greater at four days than at two days after
      Complete Freund's Adjuvant. A slight tendency in the same direction (10%) that
      was not significant was also seen in low-threshold mechanoreceptors four days
      after treatment, but not after two days. The increased velocities were confirmed
      with compound action potential recordings from ipsilateral S2 dorsal roots and
      sural nerves, in treated and control animals. Recordings showed a tendency for
      increased single-point velocities in C, Adelta and Aalpha/beta waves, with the
      upper border of the Adelta wave (i.e. the border between Adelta and Aalpha/beta
      waves) falling at a significantly higher conduction velocity in treated than
      control animals. This was seen both in S2 dorsal roots and in sural nerves. There
      was also a significant decrease in the mean electrical threshold for eliciting
      the C and Adelta components of compound action potentials of both dorsal root and
      sural nerves during inflammation. No evidence was found for a reduction in
      utilisation time for any components of the sural nerve compound action potential
      (C, Adelta or Aalpha/beta). The conduction velocity increases may be due to
      altered expression or activation/inactivation of certain ion channel types, such
      as Na(+) channels. The present experiments demonstrate that hindlimb inflammation
      caused a significant increase in conduction velocity of nociceptive but not of
      low-threshold mechanoreceptive primary afferent neurons during inflammation, as
      well as a significant decrease in the mean electrical threshold for eliciting the
      C and Adelta components of compound action potentials of both dorsal root and
      sural nerves. These changes, together with the previously described changes in
      the action potential shape of nociceptive neurons during inflammation, probably
      reflect alterations in membrane function that contribute to inflammatory
      hyperalgesia.

PMID- 11226704
TI  - P75-expressing elements are necessary for anti-allodynic effects of spinal
      clonidine and neostigmine.
AB  - Cells expressing nerve growth factor are implicated in development of
      hypersensitivity following nerve injury and cholinergic neurons are implicated in
      reduction of such hypersensitivity by alpha2-adrenergic agonists. Intrathecal
      injection of the cell toxin, saporin, linked to an antibody to the low-affinity
      nerve growth factor, p75 (192-IgG saporin), an agent which destroys cholinergic
      neurons in the brain, was used in the current study to further elucidate these
      mechanisms. Mechanical hypersensitivity was established in rats by ligation of
      the L5 and L6 spinal nerves. Animals were pretreated with intrathecal saline or
      192-IgG saporin, and one week later received intrathecal clonidine or
      neostigmine. Spinal cords were removed for acetylcholine and norepinephrine
      analysis and for cholinergic and p75 immunohistochemistry. Treatment with 192-IgG
      saporin had no effect on mechanical hypersensitivity following spinal nerve
      ligation, but blocked the anti-hypersensitivity effects of intrathecal clonidine
      and neostigmine. Destruction of p75-expressing fibers in the superficial dorsal
      horn by 192-IgG saporin was not accompanied by changes in acetylcholine or
      norepinephrine content or by reduction in cholinergic neuronal number in the
      spinal cord dorsal horn. Unlike in the brain, 192-IgG saporin does not destroy
      cholinergic neurons in the spinal cord dorsal horn and cannot be used as a tool
      for this purpose. P75-expressing elements are not necessary for the maintenance
      of mechanical hyperalgesia in this model of neuropathic pain, but their
      destruction disrupts the targets or circuitry activated by alpha2-adrenergic and
      cholinergic agents to reduce hypersensitivity.

PMID- 11226706
TI  - Calcium channels coupled to neurotransmitter release at dually innervated
      neuromuscular junctions in the newborn rat.
AB  - We studied the effect of several calcium channel blockers (omega-Conotoxin-GVIA,
      1 and 3microM; omega-Agatoxin-IVA, 100nM; Nitrendipine, 1 and 10microM) on evoked
      transmitter release at singly and dually innervated endplates of the levator
      auris longus muscle from three- to six-day-old rats. In dually innervated fibers,
      a second endplate potential may appear after the first one when we increase the
      stimulation intensity. The lowest and highest endplate potential amplitudes are
      designated "small endplate potential" and "large endplate potential",
      respectively. The percentage of doubly innervated junctions remains almost
      constant throughout the age range examined. Nevertheless, the percentage of
      junctions innervated by three or more terminal axons drops, whereas the singly
      innervated junctions increase. Therefore, between postnatal days 3 and 6, roughly
      half the neuromuscular junctions may experience the final process of axonal
      elimination. The synaptic efficacy of the large endplate potential in dual
      junctions, measured as the mean amplitude of the synaptic potential and mean
      quantal content, was the same as in the junctions that had become recently mono
      innervated in the same postnatal period. In singly innervated fibers, the
      endplate potential size was strongly reduced by both the P/Q-type voltage
      dependent calcium channel blocker omega-Agatoxin-IVA (79.17+/-4.02%; P < 0.05)
      and the N-type voltage-dependent calcium channel blocker omega-Conotoxin-GVIA
      (56.31+/-7.80%; P < 0.05), whereas endplate potential amplitude was not
      significantly changed by the L-type voltage-dependent calcium channel blocker
      Nitrendipine. In dually innervated fibers, the P/Q-type voltage-dependent calcium
      channel blocker omega-Agatoxin-IVA and L-type voltage-dependent calcium channel
      blocker Nitrendipine increased the size of the small endplate potential (161.29+/
      47.87% and 109.32+/-11.03%, respectively; P < 0.05 in both cases) and reduced the
      large endplate potential (74.42+/-15.32% and 70.91+/-10.04%, respectively; P <
      0.05 in both cases). The N-type voltage-dependent calcium channel blocker omega
      Conotoxin-GVIA significantly increased the small endplate potential in the first
      few minutes after toxin application (at 10min: 90.23+/-17.38%; P < 0.05). This
      increase was not maintained, while the large endplate potential was strongly
      inhibited (69.25+/-7.5%; P < 0.05). In conclusion, in the dually innervated
      endplates of the newborn rat, presynaptic calcium channel types can have
      different roles in transmitter release from each of the two inputs, which
      suggests that nerve terminal voltage-dependent calcium channels are involved in
      neonatal synaptic maturation.

PMID- 11226705
TI  - Kynurenine 3-mono-oxygenase activity and neurotoxic kynurenine metabolites
      increase in the spinal cord of rats with experimental allergic encephalomyelitis.
AB  - Kynurenine 3-mono-oxygenase, one of the key enzymes of the "kynurenine pathway",
      catalyses the formation of 3-hydroxykynurenine and may direct the neo-synthesis
      of quinolinic and kynurenic acids. While 3-hydroxykynurenine and quinolinic acid
      have neurotoxic properties, kynurenic acid antagonizes excitotoxic neuronal
      death. Here we report that the expression and activity of kynurenine 3-mono
      oxygenase significantly increased in the spinal cord of rats with experimental
      allergic encephalopathy, an experimental model of multiple sclerosis. As a
      consequence of this increase, the spinal cord content of 3-hydroxykynurenine and
      quinolinic acid reached neurotoxic levels. We also report that systemic
      administration of Ro 61-8048, a selective kynurenine 3-mono-oxygenase inhibitor,
      reduced the increase of both 3-hydroxykynurenine and quinolinic acid, and caused
      accumulation of kynurenic acid. In the brain and spinal cord of the controls,
      kynurenine 3-mono-oxygenase immunoreactivity was located in granules (probably
      mitochondria) present in the cytoplasm of both neurons and astroglial cells. In
      the spinal cord of rats with experimental allergic encephalopathy, however, cells
      with a very intense kynurenine 3-mono-oxygenase immunoreactivity, also able to
      express class II major histocompatibility complex and inducible nitric oxide
      synthase, were found in perivascular, subependymal and subpial locations. These
      cells (most probably macrophages) were responsible for the large increase in 3
      hydroxykynurenine and quinolinic acid found in the spinal cords of affected
      animals. The results show that cells of the immune system are responsible for the
      increased formation of 3-hydroxykynurenine and quinolinic acid, two neurotoxic
      metabolites that accumulate in the central nervous system of rats with
      experimental allergic encephalomyelitis. They also demonstrate that selective
      kynurenine 3-mono-oxygenase inhibitors reduce the neo-synthesis of these toxins.

PMID- 11226707
TI  - Alternative splicing of a Drosophila GABA receptor subunit gene identifies
      determinants of agonist potency.
AB  - Alternative splicing of the Drosophila melanogaster Rdl gene yields four
      ionotropic GABA receptor subunits. The two Rdl splice variants cloned to date,
      RDL(ac) and RDL(bd) (DRC17-1-2), differ in their apparent agonist affinity. Here,
      we report the cloning of a third splice variant of Rdl, RDL(ad). Two-electrode
      voltage clamp electrophysiology was used to investigate agonist pharmacology of
      this expressed subunit following cRNA injection into Xenopus laevis oocytes. The
      EC(so) values for GABA and its analogues isoguvacine, muscimol, isonipecotic acid
      and 3-amino sulphonic acid on the RDL(ad) homomeric receptor differed from those
      previously described for RDL(ac) and DRC17-1-2 receptors. In addition to
      providing a possible physiological role for the alternative splicing of Rdl,
      these data delineate a hitherto functionally unassigned region of the N-terminal
      domain of GABA receptor subunits, which affects agonist potency and aligns
      closely with known determinants of potency in nicotinic acetylcholine receptors.
      Thus, using expression in Xenopus oocytes, we have demonstrated differences in
      agonist potency for the neurotransmitter GABA (and four analogues) between splice
      variant products of the Drosophila melanogaster Rdl gene encoding homomer-forming
      GABA receptor subunits.

PMID- 11226708
TI  - Vendor differences in cocaine-induced behavioral activity and hormonal
      interactions in ovariectomized Fischer rats.
AB  - Contradictory effects of ovarian hormone on cocaine-induced behaviors have been
      reported in ovariectomized Fischer rats. To determine if these discrepancies are
      based on where the rats were purchased, Charles River Laboratories and Taconic
      Fischer rats were randomly assigned to either cocaine (15 mg/kg, intraperitoneal)
      or saline treatment; and one of four hormone-pretreatment subgroups: vehicle,
      estrogen, progesterone or estrogen + progesterone. Vendor differences were
      observed in cocaine-induced locomotor activities; overall, Taconic rats
      demonstrated less locomotor activity than Charles River rats. Furthermore, vendor
      differences in ambulatory activity were also observed after steroid replacement
      treatment. In Charles River rats, estrogen + progesterone co-administration
      suppressed cocaine-induced increases in ambulatory activity when compared to
      other hormone-treated groups given cocaine. In contrast, Taconic rats showed an
      increase in ambulations after this drug/hormone treatment. Vendor differences
      were also observed in steroid effects on cocaine-induced rearing activity, where
      estrogen + progesterone and cocaine caused an increase in rearing in Charles
      River rats, but not in Taconic rats. No differences between the vendors were
      observed in saline- or cocaine-treated animals' stereotypic activity. Vendor
      differences in cocaine-induced locomotor activity were not due to differences in
      cocaine metabolism, as no differences in plasma levels of benzoylecgonine were
      observed. Interestingly, Taconic animals had overall higher plasma levels of
      corticosterone than Charles River rats. Thus, intrinsic differences between
      different lines of Fischer rats may affect the outcome of ovarian hormone
      interactions in cocaine-induced behavioral alterations.

PMID- 11226709
TI  - Microinjection of a 5-HT3 receptor agonist into the NTS of awake rats inhibits
      the bradycardic response to activation of the von Bezold-Jarisch reflex.
AB  - In the present study we investigated the effects of bilateral microinjection into
      the lateral commissural nucleus tractus solitarius (NTS) of 2-methyl-5-HT, a 5
      HT3 receptor agonist, on the bradycardic response of the von Bezold-Jarisch
      reflex of awake rats. We evaluated mainly the bradycardic response because in
      previous studies we documented that the hypotensive response of the von-Bezold
      Jarisch reflex in awake rats is secondary to the intense bradycardic response.
      The Bezold-Jarisch reflex was activated by intravenous injection of serotonin (8
      microg/kg) in awake rats before and 1, 3, 10, 20 and 60 min after bilateral
      microinjection of 2-methyl-5-HT (5 nmol/50 nl, n = 8) into the NTS.
      Microinjections of 2-methyl-5-HT into the NTS produced a significant increase in
      basal mean arterial pressure [(MAP), 97 +/- 4 vs. 114 +/- 4 mmHg), no changes in
      basal heart rate and a significant reduction in bradycardic (-78 +/- 19; -94 +/-
      24 and -107 +/- 21 bpm) and hypotensive (-16 +/- 4; -10 +/- 5 and -17 +/- 4 mmHg)
      responses to activation of the von Bezold-Jarisch reflex at 3, 10 and 20 min,
      respectively, when compared with the control value (-231 +/- 13 bpm and -43 +/- 4
      mmHg). The data of the present study suggest that serotonin acting on 5-HT3
      receptors in the NTS may play an important inhibitory neuromodulatory role in the
      bradycardic response to activation of the von Bezold-Jarisch reflex.

PMID- 11226710
TI  - Progesterone receptor isoforms expression in the prepuberal and adult male rat
      brain.
AB  - Progesterone receptor (PR) isoforms expression was determined in several regions
      of the prepuberal and adult male rat brain by using reverse transcription coupled
      to polymerase chain reaction. Rats under a 14:10-h light-dark cycle, with lights
      on at 0600 h were used. We found that in the hypothalamus of prepuberal animals
      the expression of both PR isoforms was similar, whereas PR-A expression was
      higher than that of PR-B in adults. In the cerebellum PR-B expression was
      predominant in both prepuberal and adult rats. In both ages PR-A and PR-B
      exhibited a non-significant tendency to be predominant in the hippocampus and the
      preoptic area respectively. In the frontal cortex and the olfactory bulb PR
      isoforms were expressed at a similar level. These results indicate a differential
      expression pattern of PR isoforms in the male rat brain and suggest that the
      tissue-specific expression of PR-A and PR-B is important for the appropriate
      response of each cerebral region to progesterone.

PMID- 11226711
TI  - Expression of stathmin and SCG10 proteins in the olfactory neurogenesis during
      development and after lesion in the adulthood.
AB  - Stathmin and SCG10 belong to a family of phosphoproteins associated to cell
      proliferation and differentiation. In the present study, we have analyzed
      immunocytochemically the distribution of these proteins during neurogenesis in
      the mouse olfactory system, from midgestation to adulthood. Data show that
      already at embryonic day 12, stathmin and SCG10 immunoreactivities were present
      in the olfactory and vomeronasal neurons, and their number increased greatly,
      colocalizing with neuronal specific tubulin, a marker of immature neurons. Later
      on up to adulthood, the distribution of stathmin and SCG10 became progressively
      restricted to a few immature receptor and chemosensory neurons. Significantly, in
      the olfactory epithelium, stathmin was seen in immature neurons and also in basal
      cells representing precursors of neuronal elements. Interestingly, before birth
      stathmin and SCG10 immunopositive cells were seen outside the olfactory
      epithelium, seemingly migrating toward the olfactory bulb. After regeneration in
      the adult following peripheral lesion of the olfactory epithelium, stathmin and
      SCG10 were again strongly expressed and generally colocalized with neuronal
      specific tubulin immunoreactivity. Overall these results indicate that stathmin
      and SCG10 are expressed in immature olfactory neurons as well as in the migrating
      cells generated from the olfactory epithelium, supporting the role of these
      proteins in neurogenesis and cell migration.

PMID- 11226712
TI  - Behavioural, histological and immunocytochemical consequences following 192 IgG
      saporin immunolesions of the basal forebrain cholinergic system.
AB  - Use of the selective immunotoxin; 192 IgG-saporin, is helping to elucidate the
      role of the cholinergic system in cognition by overcoming the problems of
      interpretation associated with the use of non-specific lesioning agents. In
      separate studies, we have compared the long- and short-term effects of single
      site and combined saporin lesions of the nucleus basalis magnocellularis and
      medial septal area, on spatial learning and memory in radial arm and water maze
      tasks. At 11 months, only rats with combined lesions showed deficits in both
      radial and water maze tasks, although terminal cholinergic deafferentation was
      substantial and extensive tissue loss was seen at the injection sites in both
      single and combined lesions. However, the extensive tissue loss with long-term
      lesions suggested that behavioural deficits were not solely attributable to
      cholinergic deafferentation. In contrast, when rats with combined lesions were
      tested 5 months after lesioning, no deficits were apparent, although there was
      almost complete loss of choline acetyltransferase- and nerve growth factor
      receptor-immunoreactivity in the basal forebrain with no tissue damage at the
      injection sites. This study supports existing literature that selective loss of
      cholinergic neurons in the basal forebrain does not produce behavioural
      impairments in standard tasks of learning and memory, but deficits are apparent
      when damage is non-selective as occurs late after lesioning, confounding
      interpretation of behavioural data. It further highlights potential problems with
      this immunotoxin in long-term studies.

PMID- 11226713
TI  - Role of nitric oxide in insulin-induced hypothermia in rats.
AB  - Hypothermia is a well-known phenomenon which accompanies hypoglycemia in mammals.
      The present study was designed to test the hypothesis that nitric oxide (NO)
      plays a role in insulin-induced hypothermia. The body temperature (Tb) of awake,
      unrestrained rats was measured before and after systemic infusion of insulin (2U
      x kg(-1) x h(-1)), and intracerebroventricular administration of NG-nitro-(L)
      arginine methyl ester (L-NAME, a nonselective NO synthase inhibitor, 200 microg/1
      microl). We observed a significant reduction in body temperature after insulin
      infusion. L-NAME alone caused no significant change in body temperature. When the
      two treatments were combined, no change in Tb was observed. The data indicate
      that NO plays a key role in insulin-induced hypothermia.

PMID- 11226714
TI  - Role of PAG in the antinociception evoked from the medial or central amygdala in
      rats.
AB  - The effects of stimulating the periaqueductal gray (PAG) against the rat tail
      flick reflex (TFR) was not changed significantly by the microinjection of
      lidocaine (5%/0.5 microl) into the medial (ME) or central (CE) nuclei of the
      amygdala. In contrast, lidocaine into the PAG blocked the effects from the ME or
      CE. The microinjection of naloxone (1 microg), beta-funaltrexamine (2 microg),
      propranolol (1 microg), or methysergide (1 microg), but not atropine (1 microg)
      or mecamylamine (1 microg) into the PAG significantly reduced the effects from
      the CE. The effect from the ME was not altered significantly by microinjecting
      naloxone into the PAG. Therefore, the ME or CE are unlikely to be intermediary
      stations for depression of the TFR evoked by stimulating the PAG, but the PAG may
      be a relay station for the effects of stimulating the ME or CE. The circuitry
      activated from the CE, but not the ME, utilises opioid mediation in the PAG. The
      effect from the CE depends at least on mu-opioid, serotonergic, and probably beta
      adrenergic mediation in the PAG.

PMID- 11226715
TI  - Studies on the involvement of the dopaminergic system in the 5-HT2 agonist (DOI)
      induced premature responding in a five-choice serial reaction time task.
AB  - The present experiments investigated whether the enhanced premature (impulsive)
      responding induced by DOI, [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane
      hydrochloride], a 5-HT2A/2C receptor agonist, is mediated by activation of the
      dopaminergic system and if this effect of DOI occurs in the nucleus accumbens.
      Therefore, the effects of a dopamine (D1/2) receptor antagonist given alone or
      combined with DOI were examined on the performance of rats in a five-choice
      serial reaction time (5-CSRT) task. Secondly, the effects of DOI in nucleus
      accumbens core and shell were studied, in order to find the target brain area for
      DOI-induced premature responding. The results indicate that DOI (0.1 mg/kg,
      subcutaneously) increases the number of premature responses, as found previously.
      alpha-Flupenthixol (0.03 mg/kg), a D1/2 dopamine receptor antagonist, and
      raclopride (0.015 mg/kg), a D2 receptor antagonist, attenuated the DOI-induced
      enhancement in premature responding. SCH 23390 (0.005 mg/kg), a selective D1
      receptor antagonist with little affinity to 5-HT2 receptors totally blocked the
      effect of DOI. Those doses of DA antagonists did not significantly decrease
      premature responding when given alone. On the other hand, higher doses of all of
      these dopamine antagonists increased the number of omissions and decreased the
      number of ITI hole responses. In contrast to subcutaneous administration, direct
      injections of DOI (1, 3, and 10 microg bilaterally) to the nucleus accumbens
      shell or core had no effect on premature responding. These results suggest that
      the activation of the dopamine system mediates, at least in part, the effect of a
      5-HT2 agonist on premature responding, but the nucleus accumbens is not the
      primary site for this action.

PMID- 11226716
TI  - Protective effect of quinacrine on striatal dopamine levels in 6-OHDA and MPTP
      models of Parkinsonism in rodents.
AB  - Recent studies provide evidence that phospholipase A2 (PLA2) may play a role in
      the development of experimental parkinsonism. In this investigation an attempt
      was made to determine a possible protective effect of quinacrine (QNC), a PLA2
      inhibitor on MPTP as well as 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in
      rodents. For MPTP studies, adult male mice (C57 BL) were treated with MPTP (30
      mg/kg, i.p.) daily for 5 days. QNC was injected i.p. in the doses of 0, 10, 30
      and 60 mg/kg daily 30 min before MPTP in four different groups. Two other groups
      of mice received either vehicle (control) or a high dose of QNC (60 mg/kg). Two
      hours after the last injection of MPTP, striata were collected for the analysis
      of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA)
      and glutathione (GSH). For the 6-OHDA study, male Wistar rats were infused with 6
      OHDA (60 microg) in the right striatum under chloral hydrate anesthesia. The rats
      in different groups were treated with 0, 5, 15 and 30 mg/kg QNC (i.p.) for 4
      days, while first injection was given 30 min before 6-OHDA. On day 5, rats were
      sacrificed and striata were stored at -80 degrees C. Administration of MPTP or 6
      OHDA significantly reduced striatal DA, which was significantly attenuated by
      QNC. Concomitant treatment with QNC also protected animals against MPTP or 6-OHDA
      induced depletion of striatal GSH. Our findings clearly suggest the role of PLA2
      in MPTP and 6-OHDA induced neurotoxicity and oxidative stress. However, further
      studies are warranted to explore the therapeutic potential of PLA2 inhibitors for
      the treatment of Parkinson's disease.

PMID- 11226717
TI  - Sex steroid hormones exert biphasic effects on cytosolic magnesium ions in
      cerebral vascular smooth muscle cells: possible relationships to migraine
      frequency in premenstrual syndromes and stroke incidence.
AB  - Clinically, it is known that: (1) magnesium (Mg) supplementation relieves
      premenstrual problems (e.g., migraine, bloating and edema) occurring in the late
      luteal phase of the menstrual cycle; and (2) migraine syndromes, particularly in
      women, are associated with deficits in brain and serum ionized Mg levels. We
      investigated whether concentrations of sex steroid hormones, found in the serum
      during the menstrual cycle of women, are associated with changes in the levels of
      cytosolic free magnesium ions ([Mg2+]i in single cultured canine cerebral
      vascular smooth muscle cells. The resting level of [Mg2+]i in these cells was 645
      +/- 89 microM before exposure to sex steroid hormones. Exposure of these vascular
      cells to a low concentration of estrogen (10 pg/ml) failed to interfere with the
      levels of [Mg2+]i. However, exposure to estrogen, at concentrations ranging from
      40 to 200 pg/ml, induced significant loss of [Mg2+]i in a concentration-dependent
      manner. At a concentration of 200 pg/ml estrogen, the level of [Mg2+]i decreased
      approximately 30% in comparison with controls. Progesterone produced biphasic
      effects on the levels of [Mg2+]i, depending on its concentration. Exposure of the
      cultured cells to a low concentration of progesterone (0.5 ng/ml) resulted in an
      increased level of [Mg2+]i (from 690 +/- 50 microM to 753 +/- 56 microM, p <
      0.05). However, when these cells were exposed to higher concentrations of
      progesterone (i.e., from 5.0 to 20 ng/ml), the cellular levels of [Mg2+]i were
      decreased significantly. The higher the estrogen or progesterone concentration,
      the lower the levels of [Mg2+]i. In contrast, testosterone, a male hormone,
      didn't produce any significant alteration in [Mg2+]i levels in these cerebral
      vascular smooth muscle cells. These data indicate that low, physiological
      concentrations of female sex hormones, estrogen and progesterone, help cerebral
      vascular smooth cells sustain normal concentrations of [Mg2+]i, which are
      beneficial to vascular function, whereas high levels of estrogen and progesterone
      deplete, significantly, [Mg2+]i in cerebral vascular smooth muscle cells,
      possibly resulting in cerebrovasospasms and reduced cerebral blood flows related
      to premenstrual syndromes, migraine and stroke risk. Our findings could provide
      new insight into the mechanism whereby migraine occurs frequently in the late
      luteal phase in the premenstrual syndrome. In addition, our results demonstrate
      that female sex steroids but not testosterone (in physiologic concentrations) can
      exert direct effects on [Mg2+]i in cerebral vascular cells.

PMID- 11226718
TI  - Intrahippocampal infusion of antisense oligodeoxynucleotide to the GABA(A)
      receptor gamma2 subunit enhances neuropeptide Y gene expression.
AB  - The effects of hippocampal treatment with a phosphorothioate oligodeoxynucleotide
      (ODN) antisense to the gamma-aminobutyric acid (GABA)A receptor gamma2 subunit on
      neuropeptide Y (NPY) were studied. Adult male Wistar rats were treated with
      unilateral intrahippocampal infusion of gamma2 subunit antisense ODN for 5 days.
      Rats infused with mismatch ODN and naive rats served as controls. Brain sections
      were analysed for levels of NPY mRNA by in situ hybridisation, NPY
      immunoreactivity (NPY-ir) by means of immunocytochemistry, and specific NPY
      binding sites by in vitro receptor autoradiography. Following infusion of
      antisense ODN, a marked increase in cytoplasmic NPY-ir was observed in hilar
      neurones of the fascia dentata. Further, intense NPY-ir was visualised in the
      mossy fibres and in cell bodies of the entorhinal cortex and throughout the
      neocortex. High levels of NPY mRNA were detected in the same cortical areas of
      antisense treated rats. A very large increase was observed in the piriform and
      parietal areas. NPY gene expression also occurred in the granular cell layer, in
      which no NPY mRNA could be detected in normal animals. The level and distribution
      of cells displaying high levels of NPY mRNA differed among animals, perhaps as a
      result of the distinct anatomical location of ODN infusion. Finally, hippocampal
      levels of NPY specific binding increased, suggesting that NPY neurotransmission
      is markedly increased. These findings are reminiscent of reported changes in the
      expression of NPY mRNA and immunoreactivity in conditions of increased neuronal
      excitation and support the usefulness of the present animal model for the study
      of epileptic phenomena.

PMID- 11226719
TI  - Sexual diergism in rat hypothalamic-pituitary-adrenal axis responses to
      cholinergic stimulation and antagonism.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis has differential physiological
      activity in male and female animals (sexual diergism). Central cholinergic
      systems stimulate this endocrine axis. In the present study we investigated
      muscarinic and nicotinic cholinergic influences on HPA axis activity in male and
      female rats by pretreatment with selective cholinergic receptor antagonists
      followed by stimulation with physostigmine (PHYSO), an acetylcholinesterase
      inhibitor. Hormonal measures were plasma arginine vasopressin (AVP),
      adrenocorticotropic hormone (ACTH), and corticosterone (CORT). Male rats had
      significantly greater AVP and ACTH responses to PHYSO alone than did females.
      Scopolamine (SCOP) enhanced the AVP response to PHYSO to a greater extent in
      males than in females. In contrast, mecamylamine (MEC) enhanced the AVP response
      in females but decreased it in males. SCOP potentiated, and MEC inhibited, the
      stimulatory effect of PHYSO on ACTH in both sexes, but SCOP potentiation was
      greater in males, and MEC inhibition was greater in females. Absolute CORT
      increases following PHYSO were greater in females, but percent increases over
      baseline were greater in males. Similar to their effects on ACTH responses, MEC
      attenuated, and SCOP enhanced, CORT responses to PHYSO. These results suggest
      that cholinergic receptor subtypes may influence HPA axis activity differentially
      in male and female rats.

PMID- 11226720
TI  - Evaluation of muscle re-innervation employing pre- and post-axotomy injections of
      fluorescent retrograde tracers.
AB  - In experimental studies on peripheral nerve repair, the possibility to
      objectively compare original and post-operative innervation is of decisive
      importance for the selection of the proper nerve-reconstruction strategy.
      Herewith we report serious drawbacks encountered with the standard method of pre-
      and post-operative intramuscular injections of widely used retrograde neuronal
      tracers. Labeling of rat facial motoneurons by injection of Fast-Blue (FB; Group
      1), Dil (Group 2), or Fluoro-Gold (FG; Group 3) into the whisker pad muscles was
      followed by transection and suture of the facial nerve. Two months later, the
      same rats received Dil (Group 1), FG (Group 2), and FB (Group 3) injections with
      the same parameters as the pre-operative injections. By quantitative evaluation
      of single- and double-retrogradely labeled perikarya of facial motoneurons, we
      tried to estimate the accuracy of re-innervation. Observations through a "UV
      filter" (for FB-labeled perikarya) and a "rhodamine-filter" (for Dil-labeled
      perikarya) in Group 1 revealed an unexpected axotomy-triggered leakage of FB
      which compromised the counts. After pre-operative Dil labeling, nerve suture, and
      post-operative FG labeling (Group 2), Dil created an extracellular deposit in the
      whisker pad. Thus, the uptake of pre-operative tracer by sprouts of re-growing
      axons compromised counts of retrogradely labeled motoneurons. Employing the "UV
      filter" in Group 3 (FG-, FB-, FG+FB-labeled perikarya), the emission of FB
      obscured that of FG and also compromised cell counts. The use of filter sets
      constructed ad hoc for detection of FG and FB rendered possible an objective
      comparison.

PMID- 11226722
TI  - Malformations of cortical development and epilepsy.
AB  - Although once thought to be rare, malformations of cortical development are being
      increasingly recognized as the underlying cause of developmental delay in
      children and of epilepsy in children and young adults. Advances in neuroimaging
      and developmental neurobiology have created the tools by which these important
      malformations have been investigated. Through a symbiotic type of relationship,
      these investigations, and the search for a better understanding of these
      malformations, have led to advances in neuroimaging techniques and better
      understanding of both normal and abnormal brain development. In this review, the
      most common malformations or cortical development associated with epilepsy are
      discussed in regard to their clinical manifestations, classification, imaging
      appearance and basic neurobiology.

PMID- 11226723
TI  - Epilepsy associated with infantile hemiparesis: predictors of long-term
      evolution.
AB  - To study the evolution of epilepsy associated with infantile hemiparesis (IH) in
      relation to age and identification of factors predictive of pharmacoresistance.
      Thirty-four children with epilepsy and associated IH were followed for a period
      of 13 years and 3 months (range 5-19 years). All the patients underwent clinical
      evaluation and EEG, CT and/or MRI. Disease course was evaluated from the time of
      diagnosis of epilepsy to end of follow-up by differentiating the cases with
      severe pharmacoresistance from those with favourable outcome. Several possible
      prognostic factors were identified predicting evolution toward intractable
      epilepsy. Univariate statistical analysis by calculating odds ratio (OR) with 95%
      confidence interval (CI) and multivariate analysis by logistic regression were
      performed. Eleven cases presented severe epilepsy evolving toward
      pharmacoresistance; duration of epilepsy was always longer than 8 years. Twenty
      three cases (seven with severe epilepsy and 16 with mild epilepsy) evolved toward
      remission; in these patients epilepsy duration was shorter (2-7 years) and a
      complete remission was obtained within 12 years of age. Significant prognostic
      factors associated with pharmacoresistance included: non-vascular causes,
      cortical lesions, mixed and frequent seizures during the first two years of
      epilepsy. Our results show that surgical treatment could be considered in cases
      with unfavourable prognostis factors.

PMID- 11226724
TI  - Pseudo-TORCH syndrome or Baraitser-Reardon syndrome: diagnostic criteria.
AB  - Intracranial calcification and microcephaly, which represent the main clinical
      features of the TORCH-syndrome, can also be determined by a rare autosomal
      recessive infection-like condition named pseudo-TORCH syndrome. This emerging
      entity has been registered in eight families so far. We report on five patients
      from three unrelated Italian families affected by pseudo-TORCH syndrome.
      Reevaluation of literature allowed us to draw a specific clinical profile of the
      syndrome. Indeed, congenital microcephaly, congenital cerebral calcification,
      spasticity and seizures are the main clinical features, and have been present in
      almost all patients reported so far. On the contrary, findings resembling
      congenital infectious diseases including neonatal icterus, hyperbilirubinemia,
      thrombocytopenia, and hepatomegaly, affect less than half of the patients.
      Considering the diagnosis of pseudo-TORCH syndrome in patients with neonatal
      microcephaly and cerebral calcification is necessary since an early diagnosis may
      allow adequate genetic counseling to the families.

PMID- 11226725
TI  - CSF glutamate/GABA concentrations in pyridoxine-dependent seizures: etiology of
      pyridoxine-dependent seizures and the mechanisms of pyridoxine action in seizure
      control.
AB  - Several lines of evidence suggest that the binding affinity of glutamate
      decarboxylase (GAD) to the active form of pyridoxine is low in cases of
      pyridoxine-dependent seizures (PDS) and that a quantitative imbalance between
      excitatory (i.e. glutamate) and inhibitory (i.e. gamma-aminobutyric acid, GABA)
      neurotransmitters could cause refractory seizures. However, inconsistent findings
      with GAD insufficiency have been reported in PDS. We report a case of PDS that is
      not accompanied by an elevated cerebrospinal fluid (CSF) glutamate concentration.
      Intravenous pyridoxine phosphate terminated generalized seizures which were
      otherwise refractory to conventional anti-epileptic medicines. No seizure
      occurred once oral pyridoxine (13.5 mg/kg per day) was started in combination
      with phenobarbital sodium (PB, 3.7 mg/kg per day). The electroencephalogram (EEG)
      normalized approximately 8 months after pyridoxine was started. The patient is
      gradually acquiring developmental milestones during the 15 months follow-up
      period. The CSF glutamate and GABA concentrations were determined on three
      separate occasions: (1) during status epilepticus; (2) during a seizure-free
      period with administration of pyridoxine and PB; and (3) 6 days after suspension
      of pyridoxine and PB and immediately before a convulsion. The CSF glutamate level
      was below the sensitivity of detection (<1.0 microM) on each of the three
      occasions; the CSF GABA level was within the normal range or moderately elevated.
      The CSF and serum concentrations of vitamin B6-related substances, before
      pyridoxine supplementation, were within the normal range. We suggest that (1) PDS
      is not a discrete disease of single etiology in that insufficient activation of
      GAD may not account for seizure susceptibility in all cases and (2) mechanism(s)
      of anti-convulsive effect of pyridoxine, at least in some cases, may be
      independent of GAD activation.

PMID- 11226726
TI  - The clinical course of childhood and adolescent adrenoleukodystrophy before and
      after Lorenzo's oil.
AB  - The clinical course of Japanese patients with childhood and adolescent
      adrenoleukodystrophy (ALD) who were treated with Lorenzo's oil after the
      progression of early symptoms was investigated by Kaplan-Meier analyses. Many of
      the early symptoms, including visual, personality, hearing, mental and speech
      disturbances, had already appeared when the oil therapy was started. These early
      symptoms appeared significantly faster than bed-ridden state or dysphagia
      (P<0.01). Gait disturbance appeared faster than bed-ridden state and dysphagia
      (P<0.05), and tended to appear later than the early symptoms. These results would
      reflect the early natural course of childhood and adolescent ALD before
      treatment, and provide a basis for the evaluation of therapeutic trials for ALD.

PMID- 11226727
TI  - Gait patterns in children with spastic diplegia and periventricular leukomalacia.
AB  - Sequential changes in gait patterns were investigated retrospectively by
      analyzing the videotape recordings of 20 children with spastic diplegia and
      periventricular leukomalacia (PVL). The subjects began to walk at 1-5 years of
      age, and their walking was examined to 6-16 years of age. Many of the ambulatory
      children with spastic diplegia walked with flexed hips, knees and ankles. At the
      final walking examination, the knee was flexed during the stance phase in both
      legs and in all cases. In addition, the ankle was over-plantarflexed during the
      stance phase in nine cases or 14 legs, and dorsiflexed in 15 cases or 26 legs. At
      the initial walking, the knee was over-extended during the stance phase in seven
      cases or 12 legs, and was flexed in 15 cases or 28 legs. Also, the ankle was over
      plantarflexed during the stance phase in 14 cases or 22 legs, and dorsiflexed in
      ten cases or 18 legs. Bilateral excessive ankle plantarflexion or a recurvatum
      knee was observed in a portion of the children at the initial phase of walking
      only. In the diplegic children with PVL, the gait pattern was variable.

PMID- 11226728
TI  - Benign paroxysmal vertigo of childhood.
AB  - Benign paroxysmal vertigo of childhood (BPV) is a paroxysmal, non-epileptic,
      recurrent event characterized by subjective or objective vertigo that occurs in
      neurologically intact children. We recorded the history and the clinical aspects
      of 19 cases presenting with neurological problems to the outpatient clinic at the
      Pediatrics Department of Padova University between 1987 and 1998 and re-examined
      in 1999. Details were collected on the characteristics of their vertigo: age at
      onset, mode of onset, trigger factors, duration, frequency and recurrence of
      episodes, duration of symptoms in time and age at disappearance. An attempt was
      also made to establish any family history of migraine and kinetosis and the most
      important data were compared, when possible, with those reported in the
      literature. Differential diagnosis and pathogenetic hypothesis were also
      reported. It is worth emphasizing that it is important for pediatricians to be
      aware of these benign events to ensure a correct diagnostic approach, avoiding
      the child and family any pointless anxiety or costly and sometimes invasive
      diagnostic procedures.

PMID- 11226729
TI  - The spectrum of postinfectious encephalomyelitis.
AB  - The medical records of 52 consecutive patients diagnosed with postinfectious
      encephalitis/encephalomyelitis during the period from 1980 to 1998, including 29
      males and 23 females, were reviewed. These patients were divided into three
      groups according to their clinical and neurodiagnostic characteristics: (1) group
      I: postinfectious encephalitis, 38 patients; (2) group II: acute disseminated
      encephalomyelitis (ADEM), 13 patients; (3) group III: multiphasic disseminated
      encephalomyelitis (MDEM), one patient. Fever, headache/vomiting, seizure and
      disturbance of consciousness were common clinical features in all patients, while
      pictures of pyramidal, extrapyramidal, brainstem, and spinal cord lesions were
      more often found in the group II and group III patients than in the group I
      patients. Magnetic resonance imaging (MRI) revealed abnormal lesions in six (60%)
      of ten group I patients, but all group II (n=7) and group III (n=1) patients who
      received MRI study showed abnormal signals in various regions of the brain
      including the cerebral hemisphere, basal ganglia, brainstem and cerebellum.
      Patients with ADEM and MDEM had a longer clinical course and more neurological
      sequelae than group I patients. This study demonstrates the breadth of the
      clinical spectrum of postinfectious encephalomyelitis. Thorough clinical
      observations and appropriate neurodiagnostic studies such as MRI are crucial for
      the diagnosis.

PMID- 11226730
TI  - Magnetic resonance imaging in diplegic form of cerebral palsy.
AB  - Eighteen children with diplegic form of cerebral palsy (CP) underwent magnetic
      resonance imaging (MRI) because of the enlarged occipital horns of both lateral
      ventricles found on previous computerized tomography (CT). In 16 of them squint
      was present. MRI in flow attenuated inversion recovery (FLAIR) and turbo spin
      echo (TSE) modes (T2 weighted images) best showed white matter lesions in
      occipital areas in all patients with squint, while no white matter changes could
      be detected in CT (in retrospect), thus proving the superiority of MRI in
      examining CP children. The authors postulate that the hemispheric occipital
      lesion causing impairment of visual co-ordination may result in squint.

PMID- 11226731
TI  - Bax-induced apoptosis not demonstrated in the congenital toxoplasmosis in mice.
AB  - A prominent neuropathological change observed in a murine model of congenital
      toxoplasmosis is cerebral cortical hypoplasia. In the early embryonic life of
      toxoplasmosis mice, the number of apoptotic cell observed in cerebral cortex is
      increased, indicating that increased number of apoptotic cells might relate to
      the pathogenetic mechanism of the cortical hypoplasia. Immunohistochemical
      expression of apoptosis-related factors, Bcl-2 and Bax has been studied in fetal
      murine brains infected with toxoplasma and in controls. Paraffin sections of the
      fetal brains on embryonic day (ED) 10, 12, 14, 16 and 18 were applied for the
      immunostains of Bcl-2 and Bax. Totally, 47 experimental animals (ED10: n=8, ED12:
      n=6, ED14: n=12, ED16: n=6, ED18: n=15) and 48 control animals (ED10: n=6, ED12:
      n=8, ED14: n=9, ED16: n=9, ED18: n=16) were examined. Bcl-2 positive cells were
      detected on ED10, whereas Bax positive cells appeared on ED14. No difference of
      Bcl-2 and Bax expression between toxoplasmosis and control groups was detected,
      suggesting that there is no clear relation between Bax-induced apoptosis and
      cortical dysplasia in congenital toxoplasmosis.

PMID- 11226732
TI  - Varicella-associated acute necrotizing encephalopathy with a good prognosis.
AB  - A patient with acute necrotizing encephalophathy (ANE) following varicella
      infection with a good prognosis is reported. A somatosensory evoked magnetic
      field (SEF) study using a 37-channel-magnetoencephalography system demonstrated
      normal latency and strength of the first component (N20m) elicited by median
      nerve stimulation, despite bilateral symmetrical thalamic lesions on MRI. The
      normal SEF findings and the good prognosis suggested a reversible breakdown of
      the blood-brain barrier, and an edematous process as the brain pathology.
      Furthermore, our results support the idea of distinct generators for the three
      earliest cortical SEF components (N20m, P30m, N45m).

PMID- 11226733
TI  - A Japanese girl with leukoencephalopathy with vanishing white matter.
AB  - A Japanese girl with peculiar leukoencephalopathy was reported. Following normal
      development until 1 year of age, she showed progressive neurological
      deterioration with ataxia, epilepsy, pyramidal tract signs and choreic movement.
      Serial brain computed tomographies (CTs) revealed markedly low density and
      progressive volume loss in whole white matter. In extensive laboratory
      investigations, the level of glycine in the urine was elevated. She died at the
      age of 4 years, and the neuropathological findings were comprised of severe
      extensive changes in cerebral and cerebellar white matter, such as marked
      rarefaction or cystic degeneration with axonal loss. The pontine central
      tegmental tracts were also affected. Neuronal loss was seen in the cerebellar
      cortex. These features were compatible with leukoencephalopathy with vanishing
      white matter, which was recently established as a clinical entity. To our
      knowledge, this is the first report of a non-Caucasian patient with this new type
      of leukoencephalopathy.

PMID- 11226734
TI  - Forced normalization induced by ethosuximide therapy in a patient with
      intractable myoclonic epilepsy.
AB  - Forced normalization (FN) is a well known phenomenon of acute psychosis
      accompanying seizure control. An 11-year-old boy with intractable myoclonic
      epilepsy and severe psychomotor delay experienced FN during medication of
      ethosuximide. Although his myoclonic seizures were completely controlled,
      behavioral changes, more of the manic type, became evident. EEG during this
      phenomenon showed almost normal findings. Generally, withdrawal of anti-epileptic
      drugs in patients with FN is still controversial and much debated. We could
      conclude that the physician should judge comprehensively the treatment
      considering the more favorable situation for the patient and the family.

PMID- 11226735
TI  - Translating basic aging research into geriatric health care.
AB  - Aging processes are amenable to molecular genetic analyses. Two aspects of such
      research have been selected for discussion in this paper because of current great
      interest and their relevance to human aging. Studies on telomeres have revealed
      new insights on the control of cellular replicative senescence and provided a
      means to extend the cell's life span during in vitro cultivation. Emerging
      studies on genetic biomarkers have identified genes that appear to be associated
      with longevity or with risk factors for aging-related diseases, and raised
      considerations of ways to reduce disease expression. An interchange between basic
      scientists and clinicians would encourage new thoughts on the feasibility of
      translating these fundamental studies into interventions that promote healthier
      longevity.

PMID- 11226736
TI  - The Buck Institute for age research.

PMID- 11226738
TI  - Relation of oxidative protein damage and nitrotyrosine levels in the aging rat
      brain.
AB  - An increase in oxidative stress may contribute to the development of oxidative
      protein damage in the aging rat brain. In the present study, we investigated the
      relation between nitrotyrosine levels and other oxidative protein damage
      parameters such as protein carbonyl and protein thiol, as well as oxidative
      stress parameters such as total thiol, nonprotein thiol, and lipid hydroperoxides
      in the brain tissue of young, adult, and old Wistar rats. Brain nitrotyrosine
      levels of old rats were significantly decreased compared with those of young
      rats. Young and adult rats were not significantly different as far as these
      parameters were concerned, however, brain protein carbonyl and lipid
      hydroperoxide levels of old rats were significantly increased compared with those
      of young and adult rats. On the other hand, brain tissue total thiol, nonprotein
      thiol, and protein thiol levels of old rats were significantly decreased compared
      with those of young and adult rats. The strong correlation we found between
      protein carbonyl and lipid hydroperoxide levels indicates a striking relation
      between protein oxidation and lipid peroxidation in the aging brain tissue. The
      results of this study suggest that protein carbonyl formation is both a sensitive
      and a specific marker of brain aging. However, decreased nitrotyrosine levels in
      old rats, in contradiction to the expected, may be due to mechanisms other than
      oxidative protein damage in the aging rat brain.

PMID- 11226737
TI  - Alterations of antioxidant enzymes and oxidative stress markers in aging.
AB  - In accordance with the present state of scientific knowledge, the excessive
      production of free radicals in the organism, and the imbalance between the
      concentrations of these and the antioxidant defenses may be related to processes
      such as aging and several diseases. The aging process has been described by
      various theories. In particular, the free radical theory of aging has received
      widespread attention which proposes that deleterious actions of free radicals are
      responsible for the functional deterioration associated with aging. Although, the
      relationship between lipid peroxidation and aging have been investigated
      extensively, the studies have produced conflicting results. To investigate the
      correlation between the oxidative stress and aging, we have determined the levels
      of lipid peroxidation expressed as thiobarbituric acid reactive substances
      (TBARS; MDA) and conjugated dien; oxidative protein damage as indicated by
      carbonyl content and activities of antioxidant enzymes including superoxide
      dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in a sample of
      100 healthy men and women ranging in age from 20 to 70years. In addition, vitamin
      E, C levels, reduced glutathione and sulphydryl content were determined. The
      oxidation end product of nitric oxide (nitrate) was also studied to investigate
      any role of nitrogen radicals in aging. Our data show that there is an age
      related increase in lipid peroxidation expressed as MDA and oxidative protein
      damage as indicated by carbonyl content. Aging is not linked to a decline in
      antioxidant enzymes except GPx. Our data suggests that the level of oxidative
      stress increase cannot entirely be attributed to a decrease in the activities of
      antioxidant defense system and probably various factors may contribute to this
      process.

PMID- 11226739
TI  - Ultrastructural study of rat hippocampus after chronic administration of aluminum
      L-glutamate: an acceleration of the aging process.
AB  - An ultrastructural study of rat hippocampus was performed on young (group 1) and
      old (group 4) rats receiving daily subcutaneous injections of aluminum L
      glutamate and on old untreated rats (group 5). Young controls were treated with
      sodium L-glutamate (group 2) and physiological saline (group 3). Group 1 showed
      vacuolated astrocytes with numerous lipofuscin deposits, mitochondrial swelling,
      a thinning of the myelin sheath, and many multivesicular bodies invading the
      cytoplasm. Cellular structure did not appear to be affected in groups 2 and 3.
      Group 4 showed swollen mitochondria, a demyelination process in axonal regions,
      sizable perivascular oedema with vessel retraction and gliofilament bundles. In
      this group, lipofuscin deposits in astrocytes were associated with multivesicular
      bodies that thinned the myelin sheath to the breaking point; however, no
      excitotoxic glutamate-induced effects were observed. In group 5, extreme
      cytoplasmic vacuolation was observed, with massive mitochondrial swelling,
      considerable thinning of the myelin sheath (at times to the breaking point),
      sizable vacuolar degeneration and gliofilament bundles. These results indicate
      that ultrastructural alterations in the hippocampus, such as cell vacuolization,
      massive mitochondrial swelling and the demyelination process, occur with aging
      and independently of aluminum intoxication. Similar alterations were observed in
      aluminum L-glutamate-intoxicated young rats, but not in controls. These results
      are consistent with aluminum-induced acceleration of the aging process.

PMID- 11226740
TI  - Tuberculosis in aged gammadelta T cell gene disrupted mice.
AB  - In young mice exposed to aerosol infection with Mycobacterium tuberculosis
      removal of the gammadelta T cell population by targeted gene disruption does not
      affect the expression of host resistance, but does influence the integrity of the
      early granulomatous response. The current study demonstrates that in aged
      gammadelta T cell gene disrupted mice similar immunopathologic changes ensued in
      both gene knockout and wild type control mice. Changes in cell surface marker
      expression, evident in other gene knockout models, was not observed in the aged
      gammadelta T cell knockout mice. These data imply that gammadelta T cell
      functions previously observed in young mice become much less important as the
      animal ages.

PMID- 11226741
TI  - Involvement of mu class glutathione S-transferase subunit M2 (rGST M2) levels in
      the initiation and promotion of hepatocellular carcinogenesis in old rats.
AB  - Age-associated differences in the response of the initiation and promotion of
      hepatocellular carcinogenesis in the rat were analyzed. Male Wistar rats 5 and 18
      months-old were used throughout. They underwent an experimental design of
      multistage model of hepatocarcinogenesis: hepatic cells were initiated with the
      complete carcinogen Aflatoxin B1 (0.5mg/Kg b.w.) and the promotion was performed
      through a combined treatment of proliferation (partial hepatectomy, 65%) and
      administration of the tumorigenic promoter phenobarbital (0.1% in drinking water
      for 21 days). After the treatment, rats were sacrificed and the following
      parameters were determined: activity and subunit composition of the glutathione S
      transferase enzyme system, the number of liver preneoplastic foci and the
      proliferation cell index. The combined treatment (initiation + promotion) lowered
      the expression of the mu class GST (rGST M1, rGST M2). The inhibition in rGST M2
      in old animals (which in basal conditions had already been lower) was
      significant. On the other hand, the treatment increased the alpha class GST (rGST
      A, rGST A3). The number of preneoplastic foci was higher in old rats (number of
      foci/cm(2): 6.9+/-0.3 vs 3.9+/-0.3 in young rats, p< 0.05). The proliferation
      cell index did not show age-related differences. Because rGST M2 deficiency
      coexisted with induced expression of alpha class, the livers would be resistant
      to some toxic insults, being selectively sensitive to potentially genotoxic
      substances for which M2 is an essential detoxification pathway. The transition to
      a rGST M2-deficient phenotype during aging could induce higher responsiveness to
      genotoxic effects, and might favor the likelihood of further progression,
      indicating a higher susceptibility of aged animals to the development of
      carcinogenesis.

PMID- 11226742
TI  - Aging-induced changes in 24-h rhythms of mitogenic responses, lymphocyte subset
      populations and neurotransmitter and amino acid content in rat submaxillary lymph
      nodes during Freund's adjuvant arthritis.
AB  - In young (two months) and aged (18 months) male rats injected s.c. with Freund's
      adjuvant or adjuvant's vehicle 18 days earlier, 24-h variations in mitogenic
      responses, lymphocyte subsets and monoamine and amino acid content were examined
      in submaxillary lymph nodes. Mitogenic responses to concanavalin A (Con A) and
      lipopolysaccharide (LPS) were higher during the light phase of daily photoperiod.
      Old rats exhibited a suppressed or impaired mitogenic response to Con A but not
      to LPS. Acrophases of 24-h rhythm in lymphocyte subset populations in
      submaxillary lymph nodes were: 18:37-19:44h (B cells), 09:00-10:08h (T and CD4(+)
      cells) and 12:19-15:58h (CD8(+) cells). Aging augmented B cells and decreased T,
      CD4(+) and CD8(+) cells. Significant correlations were found between Con A
      activity and T cells, between lymph node 5HT content and B, T and CD8(+)
      lymphocytes, and between lymph node 5HT and taurine and GABA content. Aging
      increased lymph node 5HT content but did not modify NE content. Lymph node
      concentration of aspartate, glutamate and taurine was higher at night while that
      of GABA attained peak values at late afternoon. Old rats injected with Freund's
      adjuvant showed a higher mean value (glutamate) and smaller amplitude (glutamate,
      taurine) than their respective young controls. The results further document the
      effects of aging on the chronobiology of the immune system.

PMID- 11226743
TI  - Evidence for involvement of dysfunctional teeth in the senile process in the
      hippocampus of SAMP8 mice.
AB  - In order to evaluate the involvement of dysfunctional teeth in age-related
      deficits in hippocampal function, we examined the effect of removal of molar
      teeth (molarless condition) on neuronal degeneration and glial fibrous acidic
      protein (GFAP) expression in the hippocampus and on learning ability in a water
      maze test in young, middle-aged, and aged accelerated senescence-prone mice
      (SAMP8). The molarless condition enhanced an age-dependent decrease in both
      learning ability and the number of neurons in the hippocampal CA1 subfield and
      the age-dependent increase in the number and hypertrophy of GFAP-labeled
      astrocytes in the same subfield. These observations suggest that the molarless
      condition may be involved in the senile process in the hippocampus in SAMP8 mice.

PMID- 11226744
TI  - Effects of melatonin in perimenopausal and menopausal women: a randomized and
      placebo controlled study.
AB  - In aging humans, night levels of melatonin (MEL) decline progressively. Also
      thyroid and gonadal functions decline during aging while gonadotropins
      (luteotropic hormone (LH) and follicle stimulating hormone (FSH)) steadily
      increase. A desynchronization of pineal circadian cyclicity as expressed by the
      progressive decrease of the MEL night peak may be permissively linked to the
      onset and progression of menopause. We studied the effects of exogenous, evening
      administration of MEL on the level of hormones which are known to be involved in
      the genesis and progression of menopause. Perimenopausal and menopausal women
      from 42 to 62years of age with no pathology or medication were selected. MEL was
      measured in saliva to divide them into low, medium and high-MEL patients. Half of
      them took 3mg MEL and half of them Placebo at bedtime (10-12p.m.) in a fully
      randomized and double-blind fashion. Three and six months later blood was taken
      for determination of pituitary (LH, FSH), ovarian, and thyroid hormones I(T3 and
      T4). All women taking MEL with low basal level of MEL and/or Placebo for three
      and six months showed a significant increase in levels of thyroid hormones.
      Before initiation of the study, a negative correlation was found in all women
      between LH, FSH and basal MEL levels. Within six months of treatment, MEL
      produced a significant diminution of LH in the younger women (43 to 49year-old),
      while no effect was seen in the older women (50-62years old). A decrement of FSH
      was observed in MEL-treated women with low basal MEL levels. In addition, most
      MEL-treated women reported a general improvement of mood and a significant
      mitigation of depression. MEL decline during aging may thus signal the
      derangement of pineal and pituitary-controlled ovarian cyclicity and the
      progressive quenching of fertility in women. These findings seem to show a
      recovery of pituitary and thyroid functions in MEL-treated women, towards a more
      juvenile pattern of regulation.

PMID- 11226745
TI  - Immune effects of hormone replacement therapy in post-menopausal women.
AB  - Hormone replacement therapy (HRT) confers many health benefits to post-menopausal
      women. Despite links between estrogen and immune function prior to menopause, the
      immune status of women receiving HRT has not been rigorously investigated. This
      case-control study uses clinical laboratory assessment, flow cytometry, and
      functional assays to measure immune function. Participants included 27 post
      menopausal women taking estrogen/progestin combinations, and 22 post-menopausal
      women not receiving HRT. Compared to the (-)HRT group, the (+)HRT group had more
      B-cells (p<0.05), higher mitogen-induced T-cell proliferation (p<0.05), and
      higher levels of induced TNF-alpha (p<0.05). There was a trend towards a lower
      proportion of CD4+ T-cells expressing the activation marker CD25+ (p<0.10). These
      findings represent a reversal of immune alterations associated with normal aging,
      suggesting that preservation or improvement of immune function may be associated
      with the use of HRT.

PMID- 11226746
TI  - Serum concentrations of zinc and selenium in elderly people: results in healthy
      nonagenarians/centenarians.
AB  - Trace elements such as zinc (Zn) and selenium (Se) play an important role in
      maintaining the metabolic homeostasis in elderly people and the risk of
      deficiency seems to increase in proportion to the age. Zn and Se concentrations,
      as indices of the micronutrient status in healthy subjects over 90 years, are
      scarcely analyzed and could represent a model for studying the physiology of
      successful aging. Our aim was to investigate Zn and Se concentrations in the
      healthy persons over the age of 90 years. One hundred and fifty two subjects
      volunteered for the study. They were divided into two groups: 90 non
      institutionalized nonagenarians/centenarians (91-110 years) (group A) and 62
      elderly subjects (60-90 years) used for comparison (group B). Serum
      concentrations of Zn and Se were determined, respectively, by flame atomic
      absorption spectrophotometry (FAAS) and electrothermal atomic absorption
      spectrophotometry (ETAAS). The effect of age and sex on ion concentrations was
      investigated. Mean values+/-standard deviation of Zn and Se concentrations in the
      group A were 11.97+/-2.00 and 0.87+/-0.28 micromol/l, respectively. A significant
      decrease of Se and Zn values was demonstrated in group A, when compared with
      group B, in both males and females. However, 84.4% of the 'healthy'
      nonagenarians/centerians had both Zn and Se concentrations equal to or greater
      than the lowest values of the elderly group and only 3.3% of cases showed both Zn
      and Se deficiencies. Consequently, a prospective and follow-up evaluation of Zn
      and Se could be proposed as a good index for a correct monitoring of the
      micronutrient deficiencies, that could represent an early sign of disease.

PMID- 11226747
TI  - Serum heat shock protein and anti-heat shock protein antibody levels in aging.
AB  - We have previously reported the presence of Hsp60 and Hsp70 in the peripheral
      circulation of normal individuals. Given that the capacity to generate stress
      proteins declines with age, this study measured Hsp60 and Hsp70 levels in the
      sera of 60 individuals aged between 20 and 96 years. Levels of anti-human Hsp60,
      anti-human Hsp70 and anti-mycobacterial Hsp65 antibody were also measured.
      Senieur-approximated elderly subjects were well and randomly selected from the
      Belfast Elderly Longitudinal Free-living Aging STudy (BELFAST). Samples from
      younger individuals were obtained from the Northern Ireland Blood Transfusion
      Service. Hsp60, anti-Hsp60, anti-Hsp70 and anti-mycobacterial Hsp65 antibodies
      were detected in all samples, whereas Hsp70 was detectable in only 46 of the
      samples analysed (77%). Regression analysis revealed a progressive decline in
      Hsp60 (759ng/ml < 40 years; 294ng/ml > or = 90 years) and Hsp70 (400ng/ml < 40
      years; 20ng/ml > or = 90 years) levels with age whereas no relationship was
      apparent for anti-Hsp60 and Hsp65 antibody levels. Hsp70 antibody levels tended
      to increase with age (115U/ml < 40 years; 191U/ml > or = 90 years). This study in
      Senieur-approximated subjects demonstrates an apparent decrease in Hsp60 and
      Hsp70 with increasing age that does not appear to be related to anti-heat shock
      protein antibody status. These findings support in vitro work that demonstrates
      an age-related reduced ability to respond to stress. Further studies are required
      to understand the basis for declining serum Hsp60 and Hsp70 levels in aging and
      to elucidate their origin and role in the maintenance of homeostasis and
      resistance to environmental challenges.

PMID- 11226749
TI  - Age- and body mass index-related changes in cutaneous shear wave velocity.
AB  - BACKGROUND: The in vivo visco-elastic characteristics of skin depend on a series
      of physiopathological parameters. Among them, the age-related intrinsic tensile
      properties and the preconditioning of the tissues set under tension by the
      hypodermal volume might be of importance. AIMS: To revisit the influence of age
      and body mass on the firmness and mechanical anisotropy of the skin as determined
      by the velocity of the shear wave propagation. METHOD: Resonance running time
      measurements (RRTM) were performed on the mid volar forearm in 110 adults of both
      sexes. In each subject 16 RRTM were collected at four different precise angles
      with regard to the limb axis. We recorded the lowest, the highest and the mean
      multidirectional RRTM as well as the coefficient of variation (CV) of the latter
      value. In addition, the body mass index (BMI) was calculated. RESULTS: Age and
      BMI did not influence the minimum RRTM. In contrast, the maximum RRTM as well as
      the mean and CV of the multidirectional RRTM, significantly rose in a
      progressively increasing proportion of the subjects older than 60 years. These
      changes were only encountered in subjects with a normal BMI ranging from 18 to
      25. Sex-related differences were not disclosed. CONCLUSIONS: The intrinsic skin
      tension lines identified by the minimum RRTM are not significantly altered with
      age and BMI variations. In contrast, skin laxity identified by larger maximum and
      mean multidirectional RRTM may increase after 60 years of age in subjects with a
      normal BMI. This is accompanied by increased skin mechanical anisotropy
      identified by CV values of the multidirectional RRTM over 40%.

PMID- 11226748
TI  - Donepezil-induced REM sleep augmentation enhances memory performance in elderly,
      healthy persons.
AB  - Previous research in younger individuals has shown that acetylcholinesterase
      inhibitors may enhance REM sleep. The present study indicates that in the
      elderly, donepezil, an acetylcholinesterase inhibitor, also exerts a marked
      effect on REM sleep parameters--percentage of REM sleep and REM density were
      increased whereas REM latency was reduced. In addition, we also found a
      correlation between memory performance and REM sleep. Based on these findings, we
      conclude that there is an interrelationship between cognitive performance and
      amount of REM sleep in elderly humans as has been previously shown in animals and
      young adults.

PMID- 11226750
TI  - Localization and pharmacological characterization of voltage dependent calcium
      channels in cultured neocortical neurons.
AB  - The physiological significance and subcellular distribution of voltage dependent
      calcium channels was defined using calcium channel blockers to inhibit potassium
      induced rises in cytosolic calcium concentration in cultured mouse neocortical
      neurons. The cytosolic calcium concentration was measured using the fluorescent
      calcium chelator fura-2. The types of calcium channels present at the synaptic
      terminal were determined by the inhibitory action of calcium channel blockers on
      potassium-induced [3H]GABA release in the same cell preparation. L-, N-, P-, Q-
      and R-/T-type voltage dependent calcium channels were differentially distributed
      in somata, neurites and nerve terminals. omega-conotoxin MVIIC (omega-CgTx MVIIC)
      inhibited approximately 40% of the Ca(2+)-rise in both somata and neurites and
      60% of the potassium induced [3H]GABA release, indicating that the Q-type channel
      is the quantitatively most important voltage dependent calcium channel in all
      parts of the neuron. After treatment with thapsigargin the increase in cytosolic
      calcium was halved, indicating that calcium release from thapsigargin sensitive
      intracellular calcium stores is an important component of the potassium induced
      rise in cytosolic calcium concentration. The results of this investigation
      demonstrate that pharmacologically distinct types of voltage dependent calcium
      channels are differentially localized in cell bodies, neurites and nerve
      terminals of mouse cortical neurons but that the Q-type calcium channel appears
      to predominate in all compartments.

PMID- 11226751
TI  - Colocalization of androgen, estrogen and cholinergic receptors on cultured
      astrocytes of rat central nervous system.
AB  - By means of immunohistochemical and electrophysiological methods, we have
      investigated the presence of androgen receptors on astrocytes in explant and
      primary cultures from various regions of rat central nervous system. Our studies
      have shown that a great number of astrocytes and neurones express androgen
      receptors as recognized by a specific monoclonal antibody. Immunoreactivity was
      mainly distributed over the soma of the astrocytes, the nuclei being intensely
      stained. In contrast, glial processes were only faintly stained or not stained.
      Double-immunostaining studies have provided evidence for a colocalization of
      androgen and estrogen alpha- and beta-receptors on many astrocytes. Furthermore,
      there was also a coexistence of glial androgen receptors with cholinergic
      muscarinic and nicotinic sites. Our immunohistochemical findings are supported by
      electrophysiological investigations demonstrating that 5alpha-androstan, 17beta
      estradiol as well as the cholinergic agonists muscarine and nicotine caused
      hyperpolarizations on the same astrocytes. Our studies suggest that there is a
      coexistence of functional receptors for androgen, estrogen as well as for the
      cholinergic agonists on glial cells. Further investigations are needed to
      elucidate the physiological role of glial androgen, estrogen and cholinergic
      receptors and to define their function in neurodegenerative diseases.

PMID- 11226752
TI  - Murine homologs of deltex define a novel gene family involved in vertebrate Notch
      signaling and neurogenesis.
AB  - Notch signaling plays an important role in cell-fate specification in
      multicellular organisms by regulating cell-cell communication. The Drosophila
      deltex gene encodes a modulator of the Notch pathway that has been shown to
      interact physically with the Ankyrin repeats of Notch. We isolated four distinct
      cDNAs corresponding to mouse homologs of deltex - mouse Deltex1 (MDTX1), mouse
      Deltex2 (MDTX2), mouse Deltex2DeltaE (MDTX2DeltaE), and mouse Deltex3 (MDTX3).
      Deduced amino acid sequences of these four cDNAs showed a high degree of
      similarity to Drosophila Deltex and its human homolog, DTX1 throughout their
      lengths, even though they possess distinct structural features. MDTX proteins
      formed homotypic and heterotypic multimers. We found that these genes were
      expressed in the central, peripheral nervous system and in the thymus,
      overlapping with those of mouse Notch1. In mammalian tissue culture cells,
      overexpression of any of the four mouse deltex homologs suppressed the
      transcriptional activity of E47, a basic helix-loop-helix (bHLH) protein, in a
      manner similar to suppression by an activated form of human Notch1 or human DTX1.
      In addition, overexpression of MDTX2 and MDTX2DeltaE in C2C12 cells under
      differentiation-inducing conditions suppressed the expression of myogenin, one of
      the myogenic transcriptional factors; this was also similar to a previously
      reported activity of constitutively activated Notch. Furthermore, misexpression
      of any of the MDTX genes in Xenopus embryos resulted in an expansion of the
      region expressing the neural cell adhesion molecule (N-CAM) gene, a marker for
      the neuroepithelium. Collectively, our results suggest that these mouse deltex
      homologs are involved in vertebrate Notch signaling and regulation of
      neurogenesis.

PMID- 11226753
TI  - Prenatal stress and postnatal development of neonatal rats--sex-dependent effects
      on emotional behavior and learning ability of neonatal rats.
AB  - Maternal sound stress (800 Hz; 77 dB, every other minute for 15 min/day, from day
      10 to 18 of gestation), combined with forced swimming stress (15 min/day), was
      found to cause potentiation of sound-induced loss of locomotor activity, referred
      to as emotional behavior, of male offspring, but not that of female offspring, at
      4 weeks of age. Maternal stress also caused an increase in the total number of
      errors by male, but not female offspring in the water-maze test at 6 weeks of
      age. These effects of stress on emotional behavior and learning behavior were
      abolished when dams were pretreated with buspirone (30 min before the stress,
      from day 8 to 18 of gestation). Thus, prenatal stress might have sex-dependent
      effects on emotional behavior and learning ability of neonatal rats.

PMID- 11226754
TI  - Microglial response to the neurotoxicity of 6-hydroxydopamine in neonatal rat
      cerebellum.
AB  - Depletion of noradrenaline in newborn rats by 6-hydroxydopamine (6-OHDA) affects
      the postnatal development and reduces the granular cell area in the neocerebellum
      (lobules V-VII). During the first postnatal month, Bergmann glial fibers guide
      the migration of immature granule cells to the internal granule cell layer.
      Microglia and Bergmann glia may play an important role in this process, but the
      exact mechanism behind this phenomenon is not known. We studied the effect of
      systemic administration of 6-OHDA on the expression and localization on microglia
      and Bergmann glia in the neonatal cerebellum by immunohistochemistry. In the
      neocerebellum, 6-OHDA treatment caused a significant increase in the number of
      activated microglia. The increase was observed mainly in the granule cell layer
      and the cerebellar medulla. Bergmann glial cells in treated brains were
      abnormally located, did not form intimate associations with Purkinje cells, and
      the glial fibers were structurally different. Our findings indicate that a
      noradrenergic influence may be necessary for the normal maturation and migration
      of granule cells, and abnormal migration may be the result of Bergmann glia
      destruction and the activation of microglia. Activated microglia in the granule
      cell layer may be used as a marker for an injured cerebellar area.

PMID- 11226755
TI  - Cell formation in the cortical layers of the developing human cerebellum.
AB  - Cell proliferation has been studied in the human cerebellar cortex between the
      24th gestational week and the 12th postnatal month. Intensive cell formation has
      been found in the external granular layer (EGL) of the human cerebellum, where
      the highest cell proliferation rate occurs between the 28th and 34th gestational
      weeks. This is followed by a gradual decrease that lasts up to the eighth
      postnatal month. As late in development as the fifth postnatal month, still 30%
      of cells of the EGL are labeled with the monoclonal antibody Ki-67, which is
      specific for dividing cells. The width of the EGL remained unchanged from the
      28th gestational week to the end of the first postnatal month, when it starts to
      decrease and completely disappears by the 11th postnatal month. Large number of
      Ki-67 labeled cells occurs in the internal granular layer (IGL) between the 24th
      and 28th gestational weeks. From the 36th week onwards, the labeling index is
      less than 1%, although a few labeled cells have always been found in this layer
      even in the late postnatal period. Labeled cells are distributed in the entire
      width of the IGL. However, from the 34th gestational week, almost all labeled
      cells are found among and directly below the Purkinje cells. Their position, the
      nuclear features, and their occasionally stained cell processes suggest that
      those are Bergmann glial cells. There are few Ki-67 labeled cells in the
      molecular layer (ML) and in the white matter (WM) of the cerebellum throughout
      the examined period. It is likely that most of these are glial cells. Pyknotic
      index has been found to be small in all layers of the cerebellum during the
      examined period.

PMID- 11226756
TI  - Reconstruction of the transected cat spinal cord following NeuroGel implantation:
      axonal tracing, immunohistochemical and ultrastructural studies.
AB  - This study examined the ability of NeuroGel, a biocompatible porous poly [N-(2
      hydroxypropyl) methacrylamide] hydrogel, to establish a permissive environment
      across a 3 mm gap in the cat spinal cord in order to promote tissue
      reconstitution and axonal regeneration across the lesion. Animals with NeuroGel
      implants were compared to transection-only controls and observed for 21 months.
      The hydrogel formed a stable bridge between the cord segments. Six months after
      reconstructive surgery, it was densely infiltrated by a reparative tissue
      composed of glial cells, capillary vessels and axonal fibres. Axonal labelling
      and double immunostaining for neurofilaments and myelin basic protein, showed
      that descending supraspinal axons of the ventral funiculus and afferent fibres of
      the dorsal column regenerated across the reconstructed lesion. Fifteen months
      after reconstructive surgery, axons had grown, at least, 12 mm into the distal
      cord tissue, and in the rostral cord there was labelling of neurons of the
      intermediate gray matter. Electron microscopy showed that after 9 months, most of
      the regenerating axons were myelinated, principally by Schwann cells. Newly
      formed neurons presumably from precursor cells of the ependyma and/or migrating
      neurons were observed within the reparative tissue after 21 months. Results
      indicate that functional deficit, as assessed by treadmill training, and
      morphological changes following double transection of the spinal cord can be
      modified by the implantation of NeuroGel. This technology offers the potential to
      promote the formation of a neural tissue equivalent via a reparative
      neohistogenesis process, that facilitates and supports regenerative growth of
      axons.

PMID- 11226757
TI  - A role for an AP-1-like site in the expression of the myelin basic protein gene
      during differentiation.
AB  - Differentiation of oligodendrocyte progenitors into mature oligodendrocytes
      involves the timely, cell-type specific expression of a number of different
      genes. Among these, the expression of the myelin basic protein (MBP) gene closely
      parallels the course of oligodendrocyte differentiation. To understand how
      transcription of the myelin basic protein gene is controlled, binding to the
      distal end of the 5' flanking sequence of the MBP gene was investigated. Specific
      protein-DNA complexes were localized to an AP-1-like element located between 
      1230 and -1240. The protein-DNA complexes formed at this site were shown to
      change as the cells differentiated. In undifferentiated cells two complexes were
      formed but, as the cells differentiated, binding was nearly completely lost. One
      of the two complexes was shown to contain a member of the fos family of
      transcription factors but no jun family members were involved. Mutation of the AP
      1-like site resulted in loss of the complex and a change in expression of a
      reporter construct driven by the mutated promoter sequence. These results
      demonstrate a role for the AP-1-like site in repression of MBP gene expression in
      oligodendrocyte progenitor cells.

PMID- 11226758
TI  - IL-16 is differentially expressed in the developing human fetal brain by
      microglial cells in zones of neuropoesis.
AB  - Microglial cells are regulators of tissue homeostasis in the adult central
      nervous system and readily participate in pathological processes, orchestrating
      tissue remodeling. Cytokines produced by microglial cells are markers of cell
      activation and contribute to reactive processes. In this paper, we have studied
      the expression of IL-16 (leukocyte chemoattractant factor), a natural soluble
      ligand to the CD4 molecule, in human fetal brains from the 11th to the 20th(.)
      week of gestation by immunohistochemistry. Interleukin (IL)-16(+) cells were
      detected already at the 11th gestational week, accumulating with aging in
      cortical layers (P<0.0001) at the 16th and 19th week, and reaching maximum
      numbers in the 20th week. Most IL-16(+) microglia (>80%) revealed morphological
      hallmarks of activated microglia. We observed that IL-16 cells coexpress LCA
      (>80%) and MRP-8, an activation-associated Ca(2+) binding S-100 family member
      (>80%). In contrast, only few IL-16(+) cells proliferated (PCNA(+), 20-40%) or co
      expressed the HLA-DR, -DP, or -DQ antigen (<10%), and rare coexpression with CD68
      (20-40%) was detected until 17th week. No coexpression with CD4, CD8 or CD20 was
      detected. Furthermore, we observed accumulation of IL-16(+) microglia in zones of
      neuronal proliferation, migration and differentiation. Increasing numbers of IL
      16(+) cells were detected in bordering zones adjacent to the basal ganglia. Our
      data suggests that the early presence of IL-16(+) microglia exert a CD4
      independent function-mediating activation, and chemotaxis of microglia precursors
      during neuronal development. In addition, IL-16 immunoreactivity might be a
      helpful tool to determine distinct developmental stages of microglial cells
      during fetal central nervous system ontogeny.

PMID- 11226759
TI  - A comparison of intermediate filament markers for presumptive astroglia in the
      developing rat neocortex: immunostaining against nestin reveals more detail, than
      GFAP or vimentin.
AB  - The present study compares the immunopositive elements in the developing rat
      cortex between the day of birth (P0) and the 18th postnatal day (P18), after
      immunostaining against nestin, vimentin and glial fibrillary acidic protein
      (GFAP). Nestin immunostaining revealed more structural details than either
      vimentin or GFAP, or they together. While vimentin immunostaining preferred
      radial glia and GFAP preferred astrocytes, nestin immunostaining detected both.
      Stellate-shaped astrocyte-like cells were already seen at P0 and cells of typical
      astrocytic morphology were numerous at P3, and were predominating elements from
      P7, whereas GFAP-immunopositive astrocytes were very scarce even at P7, and
      became numerous only by P11, when nestin immunopositivity started to disappear.
      Nestin immunostaining revealed such structures which were not seen in GFAP- or
      vimentin immunostained sections: cell body-like structures 'hanging' at the end
      the radial fibers, seeming to divide with their fibers, or having astrocyte-like
      processes. Nestin immunostaining is therefore highly recommended for studies of
      the glial architecture in the early post-natal brain development.

PMID- 11226760
TI  - Topography of neurochemical alterations in the CNS of aged rats.
AB  - We have performed a general survey study on alterations of neurotransmitter
      related and glia-related neurochemical markers in various regions of the CNS of
      aged (30-month-old) as compared to adult (4-month-old) rats. We have found
      significant decreases in the level of neurochemical parameters related to the
      cholinergic and GABAergic systems in several regions of the CNS of aged rats.
      Only few of the alterations present at the age of 30 months, were present in a
      group of rat of intermediate age (20 months) included in the present study. Less
      widespread alterations were found concerning the glutamatergic neurotransmission
      system. Neurochemical markers related to glial cells (astrocytes and
      oligodendrocytes) showed a remarkable stability in aged rats as compared to
      neurotransmitter-related markers. Considering the various CNS areas examined in
      the present study, the spinal cord of the aged rats was the region showing the
      most profound alterations of neurochemical parameters, as compared to the various
      brain areas of the same rats. The present results suggest that moderate and
      region-specific alterations of neurotransmitter-related parameters occur during
      normal aging and that glia-related markers are fundamentally stable in the
      absence of specific pathologies.

PMID- 11226761
TI  - Dyspnea in cancer patients: prevalence and associated factors.
AB  - The objectives of this study were to determine the prevalence of dyspnea in the
      general cancer population, the intensity of the symptom as perceived by the
      patient, and the patient characteristics associated with the presence of dyspnea.
      Nine hundred and twenty-three cancer outpatients completed visual analogue scales
      (VAS) and verbal rating scales (VRS-D) to assess the intensity of their dyspnea.
      Baseline data included variables that were known covariates of dyspnea. Forty-six
      percent of the patients had some shortness of breath. Only 4% had a diagnosis of
      lung cancer and 5.4% lung metastases. Risk factors found to be significantly
      related to the presence of dyspnea were history of smoking; asthma or chronic
      obstructive pulmonary disease (COPD); lung irradiation; or a history of exposure
      to asbestos, coal dust, cotton dust or grain dust (P values from 0.001 to 0.038).
      The prevalence of dyspnea was strongly related to the number of risk factors a
      patient had (P < 0.0001). The VAS and VRS-D were significantly correlated,
      establishing concurrent validity for the VRS-D.

PMID- 11226762
TI  - The changeable nature of patients' fears regarding chemotherapy: implications for
      palliative care.
AB  - The side effects of chemotherapy are feared by cancer patients as they begin
      their treatment. In this study, we investigated patients' anticipatory fears
      about chemotherapy. We then re-assessed these fears three to six months after the
      initial interview for patients who received chemotherapy during that time. We
      also examined symptom distress at these intervals. Hair loss, vomiting,
      infection, nausea, and weight loss were ranked as the most feared side effects of
      cancer treatment for the group as they began treatment. Patients beginning
      chemotherapy endorsed frequent or intense levels of fatigue, worrying about the
      future, pain, and sleep problems. No differences were found in the reporting of
      symptoms based on gender, age, or educational level. While changes in symptom
      distress over the study period were unremarkable, changes in fears about
      chemotherapy were of interest. The most feared symptoms were re-ordered following
      the treatment experience. The endorsement of nausea and vomiting, alopecia, and
      loss of appetite decreased significantly. Thirty-five percent fewer chemotherapy
      patients reported vomiting as one of their most feared side effects; 45% fewer
      patients who received anti-emetics reported vomiting as one of their most feared
      side effects. Effective treatments, such as those that have been developed to
      treat acute chemotherapy-related emesis, can relieve the fears of patients on
      treatment. We conclude that patients' fears about treatment are fluid and
      malleable. Patients' fears of suffering related to chemotherapy treatment change
      in response to the provision of adequate management. We discuss the implications
      of these findings for palliative care education.

PMID- 11226763
TI  - Responding to SUPPORT: an academic medical center examines its end-of-life care
      practices. Study to Understand Prognoses and Preferences for Outcomes and Risks
      of Treatments.
AB  - The purpose of this exploratory study was to examine the end-of-life (EOL) care
      rendered to patients and families within a large midwestern academic medical
      center during a recent one-year period. An investigator-developed audit tool was
      used to review the final hospitalization records of 100 patients. Data were
      collected regarding demographic variables, final hospitalization, medical
      diagnoses and histories, and documented end-of-life care. Major findings included
      a majority of deaths occurring within medical services on critical care units, a
      frequent short length of stay, a majority of Do Not Resuscitate or Withdrawal of
      Support orders being written 1-3 days prior to death, an unstable health status
      prior to admission, and presence of at least one significant chronic illness in
      the past medical history. Findings are being used to address EOL care related
      issues within the institution.

PMID- 11226764
TI  - Economic evaluation of the fentanyl transdermal system for the treatment of
      chronic moderate to severe pain.
AB  - The fentanyl transdermal system (Duragesic) is an opioid analgesic indicated for
      the management of chronic moderate to severe pain. The purpose of this analysis
      is to estimate its economic value compared to two long-acting oral opioids. A
      cost-utility analysis was performed using a three-phased decision analytic model.
      The transdermal system had the highest expected cost during the first year of
      therapy ($2,491), moderately higher than the cost of a year of therapy with
      controlled-release morphine ($2,037) or controlled-release oxycodone ($2,307).
      The system also had the highest expected number of quality-adjusted life-days
      (QALDs) (244 compared to 236 for morphine and 231 for oxycodone), despite
      conservative assumptions. The fentanyl transdermal system achieved incremental
      cost-utility ratios of $20,709 (vs. morphine) and $5,273 (vs. oxycodone) per
      quality-adjusted life year (QALY) gained. In a conservative modeled analysis, the
      fentanyl transdermal system led to increased QALDs at a nominal increased cost.
      In the absence of head-to-head clinical trials, models help clarify cost and
      outcome trade-offs and provide a consistent theoretical framework for use by
      individual decisionmakers.

PMID- 11226765
TI  - Opioid poorly-responsive cancer pain. Part 1: clinical considerations.
AB  - Pain that is poorly responsive to opioid analgesics is challenging for physicians
      who deal with cancer patients. Numerous factors may influence analgesic response
      during the course of the illness. These include changing nociception associated
      with disease progression, the appearance of intractable side effects, the
      development of tolerance, the presence of neuropathic pain, the temporal pattern,
      the effects produced by the production of opioid metabolites, and many others.
      These factors influence the delicate balance between pain relief and opioid
      toxicity that must be achieved in cancer patients with pain.

PMID- 11226766
TI  - Understanding pruritus in systemic disease.
AB  - Many pruritic conditions do not originate in the skin, but are the result of
      systemic abnormality. Among the diseases that can cause pruritus are renal
      insufficiency, cholestasis, Hodgkin's lymphoma, polycythemia vera, solid tumors,
      and many others. Other pruritic conditions appear to be iatrogenic; opioid
      induced pruritus may be the most important in palliative medicine. Successful
      treatment of the underlying condition usually relieves itch. But, with time, many
      diseases progress and treatment of the cause will be impossible. Topical
      treatments may be of limited value. Strategies involving systemic treatments
      include use of antidepressants, oral opioid antagonists, or cholestyramine. There
      is no one cure for all pruritic symptoms. Better understanding of mechanisms of
      pruritus may help develop better treatments.

PMID- 11226767
TI  - Methadone analgesia in cancer pain patients on chronic methadone maintenance
      therapy.
AB  - Methadone is currently best known for its use as the maintenance drug in opioid
      addiction. The main concern when using methadone for the treatment of pain is its
      long and unpredictable half-life, which is associated with the risk of delayed
      toxicity. This may result in side effects such as sedation and respiratory
      depression if careful titration and close observation of individual patient
      responses are not performed. For this reason, methadone is often viewed as a
      second line opioid, after other opioids with a more predictable dose-response
      have been tried. We report six patients with long-term exposure to methadone as a
      treatment for heroin dependency, who were also treated with methadone for cancer
      pain. The first five patients were at least partially refractory to the analgesic
      effects of opioids other than methadone. All six patients achieved analgesia
      without sedation or respiratory depression from aggressive upward methadone
      titration. Methadone analgesia can be considered early in the course of treatment
      of patients with chronic exposure to methadone who develop new or worsening pain
      requiring opioid therapy.

PMID- 11226768
TI  - Making a difference.

PMID- 11226769
TI  - Intraoperative peripheral anterior capsulotomy to prevent early postoperative
      capsular block syndrome.

PMID- 11226772
TI  - Consultation section. Anterior capsulotomy to treat nasal decentration of the
      intraocular lens.

PMID- 11226780
TI  - Use of power modulations in phacoemulsification. Choo-choo chop and flip
      phacoemulsification.
AB  - We used power modulations in addition to new technology available from 6
      phacoemulsification manufacturers and altered our phacoemulsification techniques
      to take advantage of these technologies to significantly reduce the amount of
      ultrasound energy placed into the eye and enhance the rapidity and level of
      visual rehabilitation in patients.

PMID- 11226781
TI  - Topical anesthesia for phacoemulsification and painless subconjunctival
      antibiotic injection.
AB  - Endophthalmitis is a serious postoperative complication of phacoemulsification
      surgery. Administration of a subconjunctival antibiotic is a common method of
      prophylaxis in the United Kingdom and other countries. Injection of
      subconjunctival cefuroxime can be very painful, especially after
      phacoemulsification under topical anesthesia. Our experience is that this could
      be the only painful step in the entire operation. We evaluated a technique in
      which buffered lignocaine is injected into the subconjunctival space before the
      antibiotic injection. The technique was used in 46 eyes (46 patients) that had
      phacoemulsification under topical anesthesia. Eighty-seven percent of patients
      found the injection painless, 6.5% reported that the pain was very negligible,
      and 6.5% reported a moderate degree of pain.

PMID- 11226782
TI  - Clinical results of wavefront-guided laser in situ keratomileusis 3 months after
      surgery.
AB  - PURPOSE: To investigate the visual and refractive outcome of wavefront-guided
      laser in situ keratomileusis (LASIK) to correct myopic astigmatism. SETTING:
      Departments of Ophthalmology of the Universities of Dresden, Dresden, Germany,
      and Zurich, Zurich, Switzerland. METHODS: This prospective study comprised 35
      eyes of 28 patients who had a mean preoperative spherical refraction of -4.8
      diopters (D) +/- 2.3 (SD) and a cylinder of -1.1 +/- 0.9 D. Preoperative and
      postoperative wavefront analysis was performed with a Tscherning aberrometer. A
      scanning-spot laser with a 1.0 mm spot size and a 200 Hz repetition rate was
      used. The eye-tracking system had a response time of less than 6 milliseconds.
      The treatment area diameter ranged from 6.0 to 7.0 mm with a transition zone of
      1.0 mm. RESULTS: At 3 months, 68.0% of the eyes were within +/-0.5 D of
      emmetropia and 93.5% were within +/-1.0 D. Uncorrected visual acuity was 20/20 or
      better in 93.5% of eyes. No eye lost more than 1 line of low-contrast, glare, and
      best spectacle-corrected visual acuity (BSCVA). Supernormal vision (BSCVA of
      20/10 or better) was achieved in 16.0% of eyes. The correction of higher-order
      aberrations (spherical aberration, coma) was insufficient, with an increase
      factor of the overall root-mean-square wavefront error of 1.44 +/- 0.74. Coma was
      better corrected than spherical aberration. CONCLUSIONS: Wavefront-guided LASIK
      is a promising technique that offers the potential to correct refractive errors,
      to improve visual acuity, and to increase the quality of vision, especially under
      mesopic conditions. Studies that include selective overcorrection of different
      Zernike components are needed to achieve better correction of the aberrations.
      Prospective controlled clinical studies must clarify the major benefits of
      wavefront-guided LASIK.

PMID- 11226783
TI  - Photolysis using the Dodick-ARC laser system for cataract surgery.
AB  - PURPOSE: To report the intraoperative and postoperative results of cataract
      surgery using a pulsed Q-switched neodymium:YAG (Nd:YAG) laser. SETTING: Eye
      Clinic, Kreiskrankenhaus Bad Hersfeld, Germany. METHODS: This prospective study
      involved 100 consecutive patients who had cataract surgery between October 1998
      and May 1999. The patients were allocated to 3 groups based on the hardness of
      the nucleus using the LOCS III system: Group 1 (NO < or = 2.9), 48 patients;
      Group 2 (NO 3.0 to 3.9), 46 patients; Group 3 (NO > or = 4.0), 6 patients. Plasma
      was generated with a pulsed Q-switched Nd:YAG laser (ARC GmbH). A clear corneal
      incision of 1.25 mm provided access for the laser tip. An intraocular lens (CeeOn
      Edge [Pharmacia & Upjohn] or AcrySof [Alcon]) was implanted via a separate clear
      corneal incision. Intraoperative laser pulse rate and total energy were recorded.
      Preoperative and postoperative (2 days and 6 months) central cornea thickness was
      compared. RESULTS: In all cases, the cataract was removed within an acceptable
      time without converting to the conventional phacoemulsification technique. Mean
      total energy was 1.97 J +/- 1.43 (SD) in Group 1, 3.37 +/- 1.59 J in Group 2, and
      7.70 +/- 2.09 J in Group 3. No significant postoperative changes between
      preoperative and postoperative central pachymetry were seen in Groups 1 and 2;
      there was a 1.9% postoperative increase in central pachymetry in Group 3. This
      could be a consequence of the higher volume of intraoperative balanced salt
      solution and the prolonged procedure in this group. Six months postoperatively,
      there were no significant changes from the preoperative values. CONCLUSION:
      Photolysis of the lens nucleus can be used safely and efficiently for nuclei with
      a hardness up to NO 3.9. The energy required for lens removal was 83% less than
      that required by phacoemulsification.

PMID- 11226784
TI  - Effect of Healon5 and 4 other viscoelastic substances on intraocular pressure and
      endothelium after cataract surgery.
AB  - PURPOSE: To compare the ophthalmic viscoelastic device (OVD) Healon5 (sodium
      hyaluronate 2.3%) with 4 other commonly used OVDs during phacoemulsification and
      intraocular lens implantation in terms of influence on intraocular pressure (IOP)
      postoperatively and endothelial cells preoperatively and postoperatively.
      SETTING: Department of Ophthalmology, Ruprecht-Karls-University Heidelberg,
      Germany. METHODS: This clinical randomized prospective study, in which patients
      and observer were masked, comprised 81 eyes. Seventy-four eyes (mean patient age
      71.2 years +/- 7.8 [SD]) completed all preoperative and 5 postoperative
      examinations. The OVDs used were OcuCoat and Celoftal (hydroxypropyl
      methylcellulose 2.0%), Viscoat (sodium hyaluronate 3.0%-chondroitin sulfate
      4.0%), Healon GV (sodium hyaluronate 1.4%), and Healon5 (sodium hyaluronate
      2.3%). Intraocular pressure was measured by standard Goldmann applanation
      tonometry preoperatively and 4 to 6 and 24 hours and 7, 30, and 90 days
      postoperatively. Endothelial cell counts were done preoperatively and 90 days
      postoperatively using a Pro/Koester WFSCM contact endothelial microscope.
      Exclusion criteria were IOP greater than 21 mm Hg at the preoperative
      examination, age younger than 40 years, significant corneal pathology, and a
      history or presence of uveitis or pseudoexfoliation syndrome. RESULTS: All groups
      had increased IOP 4 hours postoperatively. The Healon5 group had the highest mean
      pressure (24.9 mm Hg) followed by the Viscoat group (23.6 mm Hg). The mean IOP in
      the other OVD groups was less than 22.1 mm Hg. These differences were not
      significant. Twenty-four hours postoperatively and at all subsequent
      examinations, mean IOP was below 20 mm Hg. The Healon5 group had the lowest mean
      endothelial cell loss (6.2%), significantly lower than in the other groups (P <
      .02). CONCLUSION: With all 5 OVDs, endothelial cell loss was found, with the
      lowest in the Healon5 group, and IOP was increased 4 to 6 hours postoperatively.
      After 24 hours, no significant increases in IOP were noted.

PMID- 11226785
TI  - Morphological appearance and size of contact zones of piggyback intraocular
      lenses.
AB  - PURPOSE: To characterize the morphology, size, and change in size of the contact
      zone of piggyback intraocular lenses (IOLs) of different materials and optic
      designs. SETTING: Department of Ophthalmology, Vienna General Hospital, Vienna,
      Austria. METHODS: In a prospective study, 9 eyes of 7 patients received piggyback
      IOLs of the following materials: poly(methyl methacrylate) (PMMA), acrylic,
      hydrogel, and silicone. The contact zone between the anterior and posterior IOLs
      was photodocumented from 1 day to 1 year after surgery using specular microscopy.
      The contact zone area was measured. RESULTS: A contact zone was present with all
      IOL materials studied. The area of contact, however, differed significantly. With
      PMMA IOLs, the contact zone was small and surrounded by Newton rings, indicating
      the tiny gap between the IOLs. With IOLs of soft material, such as silicone and
      hydrogel, it was larger than with PMMA IOLs and had a slightly irregular shape.
      With foldable acrylic IOLs, it was regular, round, and slightly larger than with
      the soft materials. The contact area enlarged primarily during the first 3 months
      after surgery. After 1 year, 2 eyes with acrylic piggyback IOLs had a membrane
      formation around the contact zone and 2 eyes developed Elschnig pearls between
      the IOLs. CONCLUSION: In piggyback IOL eyes, the shape and size of the contact
      zone were strongly dependent on the IOL material and optic design. Contact area
      enlargement seemed to be induced by capsule shrinkage. Fibrous membrane formation
      around the contact zone and Elschnig pearl formation between the piggyback IOLs
      were long-term complications of this technique.

PMID- 11226786
TI  - Wound complications associated with incision enlargement for foldable intraocular
      lens implantation during cataract surgery.
AB  - PURPOSE: To ascertain whether enlarging the incision for implantation of MA60
      intraocular lenses (IOLs) causes increased wound instability and compare the
      incidence of wound-related complications with that after SI-40NB IOL implantation
      through an unenlarged incision. METHODS: This retrospective study comprised
      operative and postoperative notes of consecutive patients who had implantation of
      an Allergan SI-40NB IOL using the Unfolder or an Alcon MA60 AcrySof IOL from
      April 30, 1999, and before. The operative reports were used to determine whether
      there were any wound problems, particularly the need to suture the wound. Records
      from the first postoperative day were reviewed for evidence of wound leak or
      other wound-related complications. RESULTS: Of the 200 eyes receiving an SI-40NB
      IOL, 3 (1.5%) required the placement of a suture during surgery to secure the
      wound. None had a wound leak 1 day postoperatively. Of the 200 eyes receiving an
      MA60 IOL, 12 (6.0%) required the placement of a suture during surgery to secure
      the wound. One eye had a wound leak 1 day postoperatively. The difference in the
      number of wound-related complications between the 2 IOL groups was significant (P
      =.01). CONCLUSIONS: Significantly more wound-related complications occurred after
      incision enlargement for implantation of MA60 IOLs than after implantation of SI
      40NB IOLs through unenlarged incisions.

PMID- 11226787
TI  - Tilt and decentration after primary and secondary transsclerally sutured
      posterior chamber intraocular lens implantation.
AB  - PURPOSE: To evaluate tilt and decentration after primary and secondary
      implantation of transsclerally sutured posterior chamber intraocular lenses (PC
      IOLs). SETTING: Dokuz Eylul University Medical School, Department of
      Ophthalmology, Izmir, Turkey. METHODS: Fifty-six consecutive eyes of 53 patients
      who had implantation of transsclerally sutured PC IOLs were prospectively
      included in the study. Intraocular lens tilt and decentration after primary (14
      eyes) and secondary (42 eyes) implantation were compared quantitatively using
      Purkinje images. RESULTS: The mean IOL tilt was 6.09 degrees +/- 3.80 (SD) in all
      eyes, 5.71 +/- 3.41 degrees in the primary implantation group, and 6.22 +/- 3.94
      degrees in the secondary implantation group. The mean IOL decentration was 0.67
      +/- 0.43 mm (range 0 to 2.5 mm), 0.59 +/- 0.38 mm, and 0.69 +/- 0.45 mm,
      respectively. There were no statistically significant differences between the
      primary and secondary implantation groups in decentration or tilt. Decentration
      greater than 1.0 mm was present in 7 eyes (16.7%) after secondary implantation
      and in 1 eye (7.1%) after primary implantation. Tilting of more than 10 degrees
      was present in 7 eyes (16.7%) and 2 eyes (14.2%), respectively. There were no
      statistically significant differences between the 2 groups in decentration
      greater than 1.0 mm (chi square = 0.194, P =.834) or in tilting greater than 10
      degrees (chi square = 0.834, P =.659). CONCLUSIONS: Clinically significant IOL
      tilt or decentration was rare after transscleral implantation. There were no
      differences in tilt or decentration between primary and secondary implantation.

PMID- 11226788
TI  - Inflammation after phacoemulsification in diabetic retinopathy. Foldable acrylic
      versus heparin-surface-modified poly(methyl methacrylate) intraocular lenses.
AB  - PURPOSE: To evaluate inflammation after cataract surgery in patients with
      nonproliferative diabetic retinopathy (NPDR) and compare results with 2
      intraocular lenses (IOLs): a foldable hydrophobic acrylic and a heparin-surface
      modified (HSM) poly(methyl methacrylate) (PMMA). SETTING: Department of
      Ophthalmology, University of Vienna, Vienna, Austria. METHODS: Patients with NPDR
      were randomized for implantation of an HSM PMMA IOL (811C, Pharmacia) through a
      6.0 mm sclerocorneal incision (30 patients) or a foldable hydrophobic acrylic IOL
      (AcrySof, Alcon) through a 4.0 mm sclerocorneal incision (32 patients). Both IOLs
      had 6.0 mm optics. All patients were treated according to a standardized
      protocol. The degree of flare in the anterior chamber was measured with the Kowa
      1000 laser flare-cell meter 1 day preoperatively and 1 day, 1 week, and 1 and 3
      months postoperatively. RESULTS: In both IOL groups, flare was highest on the
      first postoperative day and decreased to preoperative levels by 3 months after
      surgery. There was no statistically significant difference in relative flare
      values between the 2 groups. CONCLUSION: There was no difference in postoperative
      inflammation in eyes with a foldable hydrophobic acrylic IOL implanted through a
      small incision and those with a rigid HSM PMMA IOL. Postoperative inflammation
      results indicate that the lenses are equally suitable for the use in patients
      with diabetic retinopathy.

PMID- 11226789
TI  - Inflammatory cell adhesion and surface defects on heparin-surface-modified
      poly(methyl methacrylate) intraocular lenses in diabetic patients.
AB  - PURPOSE: To evaluate the incidence of surface scratches on heparin-surface
      modified (HSM) poly(methyl methacrylate) (PMMA) intraocular lenses (IOLs) and the
      possible influence of these alterations on the biocompatibility of HSM PMMA.
      SETTING: University Eye Clinic of Trieste, Trieste, Italy. METHODS: Twenty-six
      diabetic patients had phacoemulsification and implantation of an HSM PMMA IOL
      (809C, Pharmacia & Upjohn). Patients with proliferative diabetic retinopathy or
      iridopathy were excluded from the study. On postoperative days 7, 30, 90, and
      180, specular microscopy was performed to study and photograph the anterior IOL
      surface. The presence of scratches on the anterior IOL surface was assessed and
      the inflammatory cell reaction noted and graded using a semiquantitative scale.
      Finally, the location of the inflammatory cells in relation to the surface
      scratches was established. RESULTS: Scratches and other surface defects were
      found in 88.4% of cases. All patients had small cells on the IOL surface 7 days
      after surgery. At 30 days, small cells were observed in 88.4% of cases. The
      inflammatory cells were mainly located inside the scratches rather than
      throughout the IOL surface. CONCLUSIONS: This in vivo cytology study provides
      further evidence of the effectiveness of heparin surface modification in
      improving the biocompatibility of PMMA. In diabetic patients, inflammatory cells
      adhered to the exposed PMMA surface more than to the HSM surface, suggesting that
      the use of HSM PMMA in patients with conditions predisposing them to increased
      postoperative blood-aqueous barrier breakdown is beneficial.

PMID- 11226790
TI  - Subjective photic phenomena with refractive multifocal and monofocal intraocular
      lenses. results of a multicenter questionnaire.
AB  - PURPOSE: To compare the incidence and severity of photic phenomena after the
      implantation of the Array(R) (Allergan) refractive multifocal intraocular lens
      (MIOL) and a monofocal IOL. SETTING: Multicenter study at Kiel, Mainz, Karlsruhe,
      and Bremerhaven, Germany. METHODS: The study comprised 231 randomly selected
      patients from 4 study centers. The patients had had uneventful
      phacoemulsification with implantation of a refractive MIOL (n = 138) or a
      monofocal IOL (n = 93). By questionnaire, patients were asked whether they
      experienced light sensations postoperatively (light streaks, halos, flare,
      flashes, or glare) that had not been noticed preoperatively. Additional questions
      evaluated whether these phenomena had changed over time and how much they
      affected the patients' quality of life. RESULTS: Overall, 9% of patients with a
      monofocal IOL and 41% of those with an MIOL reported photic phenomena that had
      not been noticed before cataract surgery. Halos and flare were mentioned
      significantly more often by patients with MIOLs than by those with monofocal
      IOLs. There was no significant between-group difference in the mention of
      flashes. Eighteen percent of patients with MIOLs and 4% with monofocal IOLs were
      slightly or moderately bothered by the photic phenomena, whereas 5% of patients
      with MIOLs and none in the monofocal group were severely disturbed by the light
      sensations. CONCLUSION: Subjective photic phenomena were experienced
      significantly more often by patients who had refractive MIOLs than by those who
      had monofocal IOLs. The differences in the results of the 4 study centers were
      probably influenced by different patient selection criteria for the implantation
      of MIOLs.

PMID- 11226791
TI  - Effects of intraocular cefotaxime on the human corneal endothelium.
AB  - PURPOSE: To ascertain whether 0.4 mL of cefotaxime 0.25% applied intracamerally
      causes toxic alteration of the human corneal endothelium. METHODS: In this
      prospective randomized masked study, 66 patients had cataract extraction using
      phacoemulsification, a frown incision, and implantation of a poly(methyl
      methacrylate) intraocular lens. This was followed by intraocular injection of 0.4
      mL of cefotaxime 0.25% or balanced salt solution (BSS(R)). Contact specular
      microscopy and photography were performed preoperatively and 1 to 4 days and 3
      months postoperatively. RESULTS: In the cefotaxime group, the mean endothelial
      cell count was 2729 cells/mm(2) +/- 474 (SD) preoperatively, 2520 +/- 462
      cells/mm(2) 1 to 4 days postoperatively, and 2560 +/- 495 cells/mm(2) 3 months
      postoperatively. The mean endothelial cell count in the BSS (control) group was
      2657 +/- 413 cells/mm(2), 2475 +/- 384 cells/mm(2), and 2486 +/- 427 cells/mm(2),
      respectively. There was no significant difference in cell count or morphology
      between groups (P <.05). CONCLUSIONS: Intraocular application of cefotaxime
      produced no significant changes in endothelial cell count or morphology when
      compared with application of a control substance. With its broad spectrum of
      antibiotic activity, cefotaxime might be an appropriate alternative to other
      intraocularly administered antibiotics in anterior segment surgery for
      prophylaxis and management of infection.

PMID- 11226792
TI  - Surgical outcomes in adult patients after repair of anterior segment trauma
      sustained during childhood.
AB  - PURPOSE: To evaluate the outcomes and possible benefit of surgery performed on
      adults for anterior segment trauma sustained during childhood. SETTING: Private
      practice. METHODS: A retrospective review of patient records was performed. Adult
      patients who had anterior segment surgery for injuries that occurred during
      childhood were identified. The surgical outcomes were evaluated to determine
      whether intervention was beneficial in this subgroup of patients. RESULTS: Six
      patients were identified. Preoperative best corrected visual acuity (BCVA) was
      20/200 or worse in all patients. After surgery, the BCVA in 3 patients had
      improved to 20/30 or better and in 1 patient, to 20/60. The other 2 patients had
      less improvement; however, each noted subjective improvement in vision. No major
      intraoperative or postoperative complications occurred. CONCLUSION: In the
      absence of evidence of accompanying posterior segment trauma, surgery in adults
      to correct anterior segment damage from childhood trauma was safe and often
      beneficial.

PMID- 11226793
TI  - Normal values for the Pelli-Robson contrast sensitivity test.
AB  - PURPOSE: To define normal values for the Pelli-Robson contrast sensitivity test
      in different age groups. SETTING: University Eye Clinic of Kuopio, Kuopio,
      Finland. METHODS: Contrast sensitivity was measured with the Pelli-Robson
      contrast sensitivity test in 87 persons (60 women and 27 men) with a mean age of
      34.5 years +/- 20.8 (SD) (range 6 to 75 years). Results were studied by age group
      (years): 6 to 9, 10 to 19, 20 to 29, 30 to 39, 40 to 49, 50 to 59, and 60 and
      older. Of 163 eyes, both were healthy in 76 persons and 1 was healthy in 11.
      Study participants consisted of members of the staff of the Kuopio University
      Hospital Eye Clinic, medical students at the Kuopio University, and patients of
      the Strabismus and General Ophthalmology Units of the Eye Clinic and their
      accompanying persons. Two test distances were used: 1 m and 3 m. Eyes were tested
      individually; thereafter, the test was done binocularly. RESULTS: There were
      significant differences in logarithmic contrast sensitivity values among the age
      groups except on the test of the left eye at 1 m. The P values for the right eye
      at 1 m and 3 m, left eye at 1 m and 3 m, and both eyes at 1 m and 3 m were 0.003,
      0.002, 0.19, 0.043, 0.037, and 0.003, respectively. The mean test results in 1
      eye varied from 1.68 in the 60 year and older group to 1.84 in the 20 to 29 and
      30 to 39 year groups. Binocularly, the variation was from 1.73 in the 40 year
      group to 1.99 in the 30 year group. CONCLUSIONS: The Pelli-Robson contrast
      sensitivity test is a quick and reliable method in a clinical setting. Normal
      values of the test can be of help in evaluating cataract patients or patients
      having refractive surgery.

PMID- 11226794
TI  - Laser in situ keratomileusis for undercorrection and overcorrection after radial
      keratotomy.
AB  - PURPOSE: To evaluate laser in situ keratomileusis (LASIK) in the management of
      overcorrection and undercorrection after radial keratotomy (RK). SETTING:
      Instituto Oftalmologico de Alicante, Alicante, Spain. METHODS: This prospective
      study comprised 20 eyes of 13 patients. The eyes were divided into 2 groups: 11
      eyes that were overcorrected after RK and 9 eyes that were undercorrected after
      RK. Both groups were treated with LASIK after a mean interval of 22 months +/-
      8.4 (SD) (range 12 to 45 months). The follow-up was 6 months. RESULTS: Six months
      after LASIK, there was a significant decrease in the spherical equivalent in both
      groups. Ninety-one percent of eyes in the overcorrected group and 89% in the
      undercorrected group were within +/-1.0 diopter of the intended correction. There
      was a significant improvement in the uncorrected visual acuity in both groups. In
      the overcorrected group, 91% showed no change or improvement in their best
      corrected visual acuity; in the undercorrected group, 89% showed no change or
      improvement. CONCLUSIONS: Laser in situ keratomileusis was relatively safe in
      treating both overcorrection and undercorrection after RK. With proper
      intraoperative precautions, LASIK can effectively treat the residual refractive
      defects after RK.

PMID- 11226795
TI  - Laser in situ keratomileusis to correct hyperopic shift after radial keratotomy.
AB  - PURPOSE: To assess the safety and efficacy of excimer laser in situ
      keratomileusis (LASIK) to correct hyperopic shift following radial keratotomy
      (RK). SETTING: Ophthalmic Health Center, Tel Aviv, Israel. METHODS: The study
      comprised 15 eyes of 12 patients who had uneventful RK and subsequently developed
      a hyperopic shift. Laser in situ keratomileusis was performed using the Chiron
      Automated Corneal Shaper and the Nidek EC-5000 excimer laser with 5.5 mm central
      and 7.5 mm peripheral ablation zones. The corneal flap was 160 microm in
      thickness and 8.5 mm in diameter. The refractive correction corresponded to the
      patients' refractive errors. RESULTS: The mean time after RK was 10.46 years +/-
      2.21 (SD) and the mean follow-up after LASIK, 7.3 months (range 1 to 42 months).
      The mean spherical equivalent refraction was corrected from +3.08 +/- 1.02
      diopters (D) to -0.16 +/- 0.73 D after LASIK. At the last examination, 12 eyes
      (80%) had a refractive error within +/-1.00 D of emmetropia and an uncorrected
      visual acuity of 20/40 or better. No wound dehiscence, epithelial ingrowth, or
      other significant complication developed in any eye. CONCLUSIONS: Early
      postoperative results of the correction by LASIK of a hyperopic shift after RK
      are encouraging, but long-term studies of a larger population group are required
      to evaluate the method's clinical value.

PMID- 11226796
TI  - One year results of European Multicenter Study of intrastromal corneal ring
      segments. Part 1: refractive outcomes.
AB  - PURPOSE: To assess the efficacy, predictability, stability, and safety of
      correcting myopia with intrastromal corneal ring segments (ICRS, KeraVision,
      Inc.). SETTING: Twelve European investigational sites. METHODS: Patients with
      myopia of -1.0 to -6.0 diopters (D) and best spectacle-corrected visual acuity
      (BSCVA) of 20/20 or better (except in 3 eyes) were assigned to receive 1 of 5
      ICRS thicknesses (0.25, 0.30, 0.35, 0.40, or 0.45 mm). Efficacy was assessed by
      postoperative uncorrected visual acuity (UCVA), predictability of refractive
      outcome (deviation from predicted cycloplegic refraction spherical equivalent),
      and stability of refractive effect (manifest refraction spherical equivalent
      [MRSE]). Safety was assessed by maintenance or loss of preoperative BSCVA and
      induced manifest refraction cylinder. Measurements were made preoperatively and 1
      and 7 days and 1, 2, 3, 6, and 12 months postoperatively. RESULTS: One hundred
      fifty-nine ICRSs were implanted in the eyes of 107 patients (52 patients had
      bilateral implantation). Preoperatively, UCVA was worse than 20/40 in 98% of eyes
      (155/159); 12 months postoperatively, it was 20/20 or better in 63% of eyes
      (83/132) and 20/40 or better in 96% (127/132). Predicted refractive corrections
      for each ICRS thickness generally correlated with achieved corrections. At 12
      months postoperatively, 90% of eyes (124/138) were within +/-1.00 D of plano
      (MRSE). Two or more lines of BSCVA were lost in 6% of eyes (8/135); all 8 eyes
      had BSCVAs of 20/25 or better. CONCLUSION: The ICRS safely, effectively, and
      predictably reduced or eliminated low to moderate myopia. Refractive correction
      was stable through the 12 month follow-up.

PMID- 11226797
TI  - One year results of European Multicenter Study of intrastromal corneal ring
      segments. Part 2: complications, visual symptoms, and patient satisfaction.
AB  - PURPOSE: To assess intraoperative and postoperative complications, visual
      symptoms, and patient satisfaction after implantation of intrastromal corneal
      ring segments (ICRS, KeraVision, Inc.) for the correction of myopia and to
      demonstrate the reversibility and adjustability of refractive corrections with
      this method. SETTING: Twelve European investigational sites. METHODS: Patients
      with myopia of -1.0 to -6.0 diopters (D) were assigned to receive 1 of 5 ICRS
      thicknesses (0.25, 0.30, 0.35, 0.40, or 0.45 mm). Complications and visual
      symptoms were noted, and patient satisfaction was assessed at each postoperative
      visit (1 and 7 days and 1, 2, 3, 6, and 12 months). Refractive data were assessed
      after removal or exchange of the ICRS. RESULTS: Of 163 eyes of 110 patients
      enrolled, 159 eyes of 107 patients were implanted with an ICRS (52 patients had
      bilateral implantation). Intraoperative complications occurred in 2% of eyes
      (4/163 eyes in 3 patients) that were withdrawn from the study: 3 eyes had
      anterior surface perforations and 1 had a posterior microperforation into the
      anterior chamber. Most patients had no visual symptoms at 12 months; symptoms
      usually occurred rarely or sometimes and were mild in severity. At 12 months,
      good or excellent patient satisfaction was reported for 94% of eyes. Twelve ICRSs
      (8%) were removed, mainly because of undercorrection and induced astigmatism, and
      2 were exchanged. All eyes were within +/-1.00 D of the preoperative manifest
      refraction spherical equivalent. CONCLUSIONS: The ICRS was safe for correction of
      low to moderate myopia. Severe postoperative visual symptoms were rare, and
      patient satisfaction was high. The refractive correction was largely reversible.

PMID- 11226798
TI  - Effect of preoperative keratometry on refractive outcomes after laser in situ
      keratomileusis.
AB  - PURPOSE: To evaluate the effect of preoperative keratometry on the refractive
      outcome after laser in situ keratomileusis (LASIK) for myopia. SETTING:
      University Eye Clinic, Prince of Wales Hospital, Hong Kong, China. METHODS: In
      this retrospective study, the records of patients who had LASIK for myopia
      greater than -6.0 diopters (D) using the Chiron Automated Corneal Shaper and the
      Schwind Keratome-F excimer laser were reviewed. RESULTS: Laser in situ
      keratomileusis was performed in 167 eyes of 103 patients (mean age 34.7 years +/-
      7.5 [SD]). Preoperative myopic spherical equivalent (SE) refraction was -9.0 +/-
      2.0 D (range -6.0 to -13.9 D). Three months after surgery, SE refraction was 
      0.04 +/- 1.1 D (range +2.3 to -3.3 D); uncorrected visual acuity > or = 20/40 was
      present in 91.8% of 110 eyes in which emmetropia was the postoperative goal. Mean
      preoperative keratometry was 43.9 +/- 1.5 D (range 40.3 to 48.1 D). When eyes
      were stratified by the degree of preoperative myopia in 1.0 D steps, a trend
      toward greater undercorrection was noted in eyes with preoperative keratometry <
      43.5 D than in those with steeper keratometry (> 44.5 D) in all myopia groups
      except the -7.0 to -7.9 D group. This difference was statistically significant in
      eyes with a preoperative SE of -10.0 to -10.9 D and -11.0 to -11.9 D.
      CONCLUSIONS: Preoperative keratometry appeared to influence the refractive
      outcome after myopic LASIK. Eyes with flatter corneas tended to have greater
      undercorrection than eyes with similar myopia and steeper corneas. Validation of
      these findings in larger data sets using the methodology described may improve
      the predictability of current LASIK nomograms, particularly in eyes with high
      myopia.

PMID- 11226799
TI  - Reduction in intraocular pressure after laser in situ keratomileusis.
AB  - PURPOSE: To investigate whether intraocular pressure (IOP) measured on the nasal
      side is affected after laser in situ keratomileusis (LASIK). SETTING: The
      Glaucoma Service, Dr. Hong's Eye Clinic, Seoul, Korea. METHODS: In 83 patients,
      IOP was prospectively measured with the Goldmann tonometer at the central
      (Tcenter) and nasal (Tnasal) areas of the cornea before and after LASIK. The
      Tcenter and Tnasal IOP between baseline and 1, 3, and 6 months postoperatively
      was compared. The correlation between ablation depth, amount of treatment,
      refractive change, and change in central corneal thickness and Tcenter change was
      evaluated. RESULTS: Six months after LASIK, Tcenter IOP decreased 3.9 mm Hg
      (25.2%) and Tnasal IOP decreased 2.0 mm Hg (12.7%) (P < .001, P = .02,
      respectively). The Tnasal measurement was 1.8 mm Hg higher than the Tcenter
      measurement (P < .001). Significant correlation between each corneal parameter
      and the Tcenter reduction at 1 month did not continue to 6 months (P > .05).
      CONCLUSION: At each follow-up, Tnasal IOP was statistically lower than at
      baseline, although the reduction was not as great as that of Tcenter IOP. A 2 to
      3 mm Hg drop in Tnasal up to 6 months after LASIK should be expected. An
      alternative would be to measure IOP with the Tono-Pen on the nasal side to fit
      the tip to the relatively unchanged nasal side of the cornea.

PMID- 11226800
TI  - Reduction in corneal haze and apoptosis by amniotic membrane matrix in excimer
      laser photoablation in rabbits.
AB  - PURPOSE: To determine whether preserved human amniotic membrane can reduce
      corneal haze and keratocyte apoptosis induced by excimer laser photoablation in
      rabbit corneas. METHODS: Excimer photoablation was performed bilaterally in 30
      rabbits with a 6.0 mm ablation zone and 120 microm depth using the VISX Star
      laser with the phototherapeutic keratectomy (PTK) mode. One eye was randomly
      covered by preserved human amniotic membrane secured with 4 interrupted 10-0
      nylon sutures, and the other eye served as the control. The amniotic membranes
      were removed at 1 week, and corneal haze was graded with slitlamp biomicroscopy
      by 3 masked corneal specialists biweekly for the ensuing 12 weeks until the
      rabbits were killed. Another 18 rabbits were divided into 4 subgroups and
      received PTK alone, PTK with membrane, PTK with sham sutures, or PTK with
      tarsorrhaphy. All eyes were studied histologically, and 3 eyes in each group were
      studied by in situ terminal deoxynucleotidyl transferase deoxy-UTP-nick end
      labeling assay at 1, 3, and 7 days and 12 weeks, respectively. RESULTS: A
      consistent grading of differences in corneal haze scoring between the control
      corneas and the amniotic-membrane-covered corneas was noted among the 3 masked
      observers. Organized reticular post-PTK corneal haze peaked at 7 weeks in both
      groups, and the corneal haze score in the amniotic-membrane-covered group was
      significantly less than in the control group from 7 to 12 weeks (all P < .001).
      Compared to the control corneas, the amniotic-membrane-covered corneas had less
      inflammatory response at 1 and 3 days, less keratocyte apoptosis in the ablated
      anterior corneal stroma at 1, 3, and 7 days (P < .001), and less stromal
      fibroblast cellularity and epithelial hyperplasia at 12 weeks. CONCLUSIONS:
      Amniotic membrane matrix introduced at an early stage of the corneal wound
      healing process effectively reduced corneal haze induced by excimer laser
      photoablation in rabbits. Studies linking suppression of apoptosis in the acute
      wound-healing process with reduction of subsequent corneal scarring may have
      useful clinical applications.

PMID- 11226801
TI  - Healon5 viscoadaptive formulation: Comparison to Healon and Healon GV.
AB  - PURPOSE: To compare the rheological characteristics of a viscoadaptive
      viscoelastic formulation with those of 2 standard ophthalmic viscosurgical
      devices (OVDs). SETTING: Department of Ophthalmology, Johannes Gutenberg
      University, and Max Planck-Institute for Polymer Research, Mainz, Germany.
      METHODS: An independent comparative study of 3 OVDs of sodium hyaluronate
      (Healon(R), Healon GV(R), and Healon(R)5) was performed using the Advanced
      Rheometric Expansion System to analyze rheologic behavior (eg, dynamic frequency
      dependence of the complex viscosity) as well as rheological parameters (eg,
      viscosity at zero shear rate, pseudoplasticity, relaxation time, elastic and
      viscous modulus). RESULTS: Mean viscosity at zero shear rate was 243 Pas +/- 5
      (SD) for Healon, 2451 +/- 12 Pas for Healon GV, and 5525 +/- 14 Pas for Healon5.
      Mean pseudoplasticity was 173 +/- 7, 754 +/- 10, and 591 +/- 6, respectively.
      Mean relaxation time was 21 +/- 3 sec, 83 +/- 4 sec, and 88 +/- 6 sec. At low
      shear rates, viscosity and elasticity (elastic and viscous modulus) increased
      from Healon through Healon5. Healon5 exhibited a dynamic behavior of the complex
      viscosity dependent on the duration of the shear rate exposure: At low shear
      rates, it slowly built up a high viscosity. At higher shear rates, it
      demonstrated a lower viscosity that decreased further during constant exposure to
      a specific shear rate. CONCLUSIONS: Healon5 had the highest viscosity and
      elasticity when exposed to low and high shear rates. These characteristics
      maintain anterior chamber depth. Also, the high viscosity of Healon5 exhibited a
      dynamic frequency dependence. In the presence of turbulence and phaco power
      (continuous high shear rates), it became dispersive by fragmentation and formed a
      cavity with an outer retentive shell. The cohesive and dispersive properties of
      Healon5 make it the best of the 3 OVDs evaluated for use at all stages of
      phacoemulsification.

PMID- 11226802
TI  - Ultrasound biomicroscopy of chronic hypotony after cataract extraction.
AB  - Ultrasound biomicroscopy was performed with a UBM 840 (Zeiss-Humphrey) equipped
      with a 50 MHz probe on a patient with chronic hypotony 1 year after cataract
      surgery by phacoemulsification with intraocular lens implantation in the capsular
      bag. This sonographic technique, which provides high-resolution imaging of the
      anterior segment, showed aqueous humor leakage through the former scleral tunnel
      incision. Ultrasound biomicroscopy helped detect this patient's postoperative
      complication and is a good tool for diagnostic procedures in patients with
      chronic hypotony.

PMID- 11226803
TI  - Early decentration of plate-haptic silicone intraocular lenses.
AB  - We report 4 eyes of a consecutive series of 1299 that developed early
      decentration of a 10.5 mm diameter plate-haptic silicone intraocular lens (IOL)
      after uneventful phacoemulsification. All eyes had an intact continuous
      curvilinear capsulorhexis (CCC) with the IOL placed in the capsular bag. After an
      initial period of good vision, patients noted the onset of glare or monocular
      diplopia between 1 and 5 weeks after surgery. On examination, there was no
      significant anterior capsule contraction; however, the edge of the IOL optic was
      visible in the undilated pupil. There was adhesion between the anterior and
      posterior capsules at the margin of the CCC that maintained the IOL decentration.
      Decentration recurred in 1 eye after the IOL was rotated 90 degrees and
      recentered. Symptoms resolved in 3 eyes after the IOL was removed and replaced
      with a rigid IOL with a larger diameter optic.

PMID- 11226804
TI  - Massive anterior capsule shrinkage after plate-haptic silicone lens implantation
      in uveitis.
AB  - Two patients, both with bilateral uveitis, had synechiolysis, continuous
      curvilinear capsulorhexis (CCC), phacoemulsification, and in-the-bag implantation
      of a foldable single-piece plate-haptic silicone intraocular lens (IOL) in 1 eye.
      Several weeks postoperatively, massive anterior capsule shrinkage with
      obstruction of the visual axis occurred in both patients. Surgical revision was
      performed in both eyes. Both patients had CCC and phacoemulsification and
      confirmed in-the-bag acrylic IOL implantation in the second eye months after
      surgery in the first eye. Follow-up examinations showed no significant shrinkage
      of the anterior capsule opening in any eye. In patients with uveitis,
      intraoperative lens epithelial cell removal, creation of a large CCC, and careful
      selection of IOL style and material may prevent occlusion of the anterior capsule
      opening.

PMID- 11226805
TI  - Intraocular lens subluxation in a patient with facial atopic dermatitis.
AB  - A 66-year-old Japanese man presented with subluxation of a posterior chamber
      intraocular lens (IOL) caused by a rupture of part of Zinn's zonule but no
      retinal break 2 years after phacoemulsification with IOL implantation. He had a
      history of atopic dermatitis since infancy. This case presents a rare ocular
      complication of scratching and rubbing the face and eyelids because of itching
      related to atopic dermatitis.

PMID- 11226806
TI  - Reboxetine in seasonal affective disorder: an open trial.
AB  - Seasonal affective disorder (SAD), winter type, is a condition characterized by
      the annual recurrence of depressive episodes during fall/winter, alternating with
      spring/summer euthymia or hypomania. Various neurotransmitters have been
      implicated in the etiology of SAD, the strongest evidence involving serotonin.
      Recently, increasing attention has been paid to the potential role of
      catecholaminergic pathways in the pathophysiology of SAD. We investigated the
      efficacy and tolerability of reboxetine, a selective noradrenaline inhibitor, in
      patients with SAD. Eleven out of sixteen patients who were included in a 6-week
      drug surveillance during winter season experienced full remission of depressive
      symptoms. Nine patients reported a rapid relief of preexistent severe atypical
      depressive symptoms within the first treatment week. Reboxetine might therefore
      be an effective and well-tolerated treatment option for SAD patients. In
      conclusion, our preliminary results are in line with evidence from recent studies
      suggesting that catecholaminergic systems might also be involved in the
      pathophysiology of SAD.

PMID- 11226807
TI  - Weak 24-h periodicity of body temperature and increased plasma vasopressin in
      melancholic depression.
AB  - Earlier work has shown that plasma vasopressin levels of depressed patients were
      higher than those of healthy controls. The aim of the present study was to
      determine whether plasma vasopressin levels were correlated to parameters of the
      circadian rhythm. Forty-one patients with major depression and twenty-five
      controls participated in a case-control design under natural circumstances in a
      field study to investigate plasma vasopressin levels three times daily, circadian
      motor activity, and the 24-h periodicity of body temperature for five consecutive
      24-h periods. Temperature measurements consisted of at least five, but mostly six
      or more measurements every 24 h. Twenty-two percent of the patients, but none of
      the controls lacked 24-h periodicity of body temperature. In melancholic patients
      increased vasopressin levels in plasma correlated with a weak 24-h periodicity of
      body temperature. The role of vasopressin is discussed in the light of the
      present findings.

PMID- 11226808
TI  - Rapid desensitization of 5-HT(1A) receptors in Fawn-Hooded rats after chronic
      fluoxetine treatment.
AB  - Anxiety, platelet serotonin (5-HT) content and functions of the 5-HT(1A) receptor
      agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) were measured in
      Sprague--Dawley (SD) and Fawn-Hooded (FH) rats, a strain with genetically
      impaired 5-HT storage and reuptake system and a putative model of depression and
      anxiety. In addition, the effects of 7 and 16 days treatment with the selective
      serotonin reuptake inhibitor (SSRI) fluoxetine on 8-OH-DPAT-induced responses
      were studied. FH rats showed significantly higher anxiety in the social
      interaction test, and much lower platelet 5-HT content compared to SD rats. The
      efficacy of 8-OH-DPAT (15-120 microg/kg, i.v.) to induce lower lip retraction (an
      effect mediated by median raphe receptors) was increased in FH rats. In most FH
      but only a few SD rats a special neurological syndrome, clonic movement of the
      masseters and in-and-out movement of the eyeballs, was induced by 8-OH-DPAT, and
      this behaviour like other effects of 8-OH-DPAT, was completely blocked by
      pretreatment with the 5-HT(1A) receptor antagonist WAY-100635. In SD rats
      fluoxetine (10 mg/kg/day, i.p.) caused a moderate inhibition of 8-OH-DPAT-induced
      hypothermia, an effect mediated most likely by hypothalamic 5-HT(1A) receptors, (
      19% and -40% after 7 and 16 days of fluoxetine, 24 h after the last injection,
      respectively). In FH rats fluoxetine caused a rapid and complete reduction in the
      8-OH-DPAT-induced hypothermia (-65% and -91% after 7 and 16 days of fluoxetine,
      respectively). Fluoxetine caused no change in lower lip retraction but a
      reduction in the masseter-eyeball syndrome in both SD and FH rats. Our data
      provide evidence that in FH rats, median raphe 5-HT(1A) receptors are
      hypersensitive, and the hypothalamic 5-HT(1A) receptor desensitization, caused by
      SSRI antidepressants, is faster and more complete. These data support the notion
      that chronic treatment with SSRIs induces a desensitization of some 5-HT(1A)
      receptor populations, and impaired 5-HT storage and reuptake may accelerate this
      process.

PMID- 11226809
TI  - New onset diabetes and atypical antipsychotics.
AB  - As a class, the atypical antipsychotics are the first line treatment choice for
      the psychopharmacologic management of psychotic disorders. Emerging evidence
      currently suggests that at least two of the atypical antipsychotics, clozapine
      and olanzapine, and possibly quetiapine may be associated with the risk of new
      onset diabetes or serum glucose dyscontrol. Computerized Medline and Current
      Contents searches from years 1966 through June 2000 were undertaken to retrieve
      all pertinent studies and case reports of typical and atypical antipsychotics and
      glucose-insulin problems. Historically, both schizophrenia and the older
      antipsychotics medications have been reported to be associated with a similar
      risk for causing disruptions in serum glucose control. Additionally, diabetes has
      well recognized associations with a number of medical disorders such as
      cardiovascular disease; it is therefore worthy of attention. Hypothesized
      mechanisms for antipsychotic induced diabetes ranges from the antagonism of
      several neurotransmitter receptors to insulin resistance. A total of thirty-five
      cases of induced or exacerbated diabetes are presently available in the published
      literature; the vast majority of cases implicate clozapine (n=20) and olanzapine
      (n=15). In multiple cases, diabetic ketoacidosis has been the presenting symptom;
      daily atypical antipsychotic doses have been within acceptable ranges and were
      not considered to be excessive.

PMID- 11226810
TI  - Can nootropic drugs be effective against the impact of ethanol teratogenicity on
      cognitive performance?
AB  - Rats exposed pre- (PA) and postnatally (PNA) to ethanol at a dose of 1 g/kg for
      24 h developed fetal alcohol effects (FAE). This was measured using a condition
      reflex method for active avoidance with punishment reinforcement (shuttle-box) in
      which pronounced learning and memory deficits in 3-month-old rats were found
      after ethanol exposure (Vaglenova and Petkov, 1998. Fetal alcohol effects in rats
      exposed pre- and postnatally to a low dose of ethanol. Alcohol. Clin. Exp. Res.
      22(3), 697--703). In the present study the effects of piracetam (Pyramem) at a
      dose of 600 mg/kg body weight, aniracetam at 50 mg/kg, and meclophenoxate
      (Centrophenoxine) at 100 mg/kg were studied. The drugs were administered orally
      during 10 days to separate groups of naive and pre- and postnatally exposed to
      ethanol rats. All the investigated nootropic drugs showed a significant
      possibility to alleviate learning and memory disability of rats with FAE.
      Aniracetam was administered to 1-month-old rats, demonstrating a prolonged (2
      months) therapeutic effect, observed in rats aged 3 months. As previously
      reported (Vaglenova and Petkov, 1998), between male rats with FAE and controls,
      66 and 33% were 'poor learners', respectively. In all nootropic treatment groups
      the percentage of 'poor learners' dropped to 28%. The positive effects of
      piracetam, aniracetam and meclophenoxate suggest that these drugs could be used
      for both treatment and prophylactic of FAE-connected disturbances of cognition.

PMID- 11226811
TI  - Role of dopaminergic and serotonergic systems on behavioral stimulatory effects
      of low-dose alprazolam and lorazepam.
AB  - Several recent studies have demonstrated that alprazolam and lorazepam,
      administered at low doses to healthy volunteers, improve cognitive functions and
      psychomotor performances. Paradoxical effects of low-dose benzodiazepines have
      been also observed in mice, in experimental pharmacology. The aim of this work
      was to determine, in rat, the effect of similar low-doses of benzodiazepines on
      spontaneous locomotor activity and performance in the elevated zero-maze, and to
      investigate the underlying neurobiological mechanisms. The dose-effect and the
      time-course of the action were studied for both compounds. Spontaneous locomotor
      activity was measured using a photoelectric actimeter. The level of anxiety of
      the animals was assessed in the elevated zero-maze. Dopamine, serotonin, and
      their metabolites were assayed in the extracellular striatal fluid of the awake
      rat, obtained by microdialysis, by HPLC--EC. Spontaneous locomotor activity
      observed in rats given low-dose alprazolam and lorazepam evidenced a stimulatory
      effect only with alprazolam. The effect was maximum 90 min after administration
      of 0.0050 mg/kg alprazolam. An anxiogenic-like action was evidenced with the
      elevated zero-maze for the two compounds. We observed a statistically significant
      increase in striatal dopamine concentrations only with alprazolam, during the
      period corresponding to the behavioral stimulatory effects. We also showed a
      marked trend towards increased levels of serotonin with alprazolam but this
      modification was not significant, in spite of statistically significant
      variations of 5-HIAA. In the rat, behavioral stimulatory effects of low-dose
      benzodiazepines is evidenced with alprazolam but not lorazepam. This effect could
      be explained, at least in part, by increased extracellular dopamine
      concentrations in the striatum. Their different structures could explain the
      different pattern observed for the two benzodiazepines.

PMID- 11226812
TI  - Early amygdala damage in the rat as a model for neurodevelopmental
      psychopathological disorders.
AB  - Neurodevelopmental disorders in medial temporal lobe structures may underlie
      psychopathological diseases such as schizophrenia and autism. To construct an
      animal model for these developmental disorders, social and non-social behavioural
      responses were assessed in rats with ibotenic acid lesions of the (baso-)lateral
      and central amygdala or ventral hippocampus, induced early in life. Lesioning the
      amygdala on day 7 after birth resulted in a variety of behavioural disturbances
      later in life, whereas after similar lesions on day 21 after birth no
      disturbances developed, except for deficits in social behaviours. Lesioning the
      hippocampus led to much less disturbances. The results show that amygdala and
      hippocampus damage at a specific point early in life results in enduring
      behavioural disturbances that become more manifest after puberty. In particular,
      lesions of the amygdala on day 7 of life may serve as a rat model with face and
      construct validity for neurodevelopmental disorders in studying psychopathology.

PMID- 11226813
TI  - Glutamate receptor antagonists differentially affect the protective activity of
      conventional antiepileptics against amygdala-kindled seizures in rats.
AB  - LY 300164 (5 mg/kg), a selective non-competitive antagonist of AMPA/kainate
      receptors, exerted a significant anticonvulsant effect in amygdala-kindled rats,
      being ineffective at 2 mg/kg. LY 235959 (1--5 mg/kg), a selective competitive
      antagonist of NMDA receptors, failed to modify behavioral and electrographic
      correlates of kindled seizures. Amygdala-kindled seizures were inhibited by
      conventional antiepileptics, their lowest effective doses were: 20 mg/kg for
      carbamazepine and phenobarbital, 50 mg/kg for diphenylhydantoin, and 100 mg/kg
      for valproate magnesium. The combined treatment of the AMPA/kainate antagonist (2
      mg/kg) with valproate at sub-effective doses (25--75 mg/kg) resulted in the
      reduced severity and duration of kindled seizures. Also, a clear-cut protective
      effect was observed when LY 235959 was co-administered with diphenylhydantoin (40
      mg/kg). Any interaction at the pharmacokinetic level can be excluded because
      neither LY 300164 nor LY 235959 interfered with the free plasma levels of
      valproate or diphenylhydantoin, respectively. The combination of the AMPA/kainate
      receptor antagonist (2 mg/kg) with valproate (75 mg/kg) did not impair
      performance of rats in the rotorod test (motor co-ordination) or passive
      avoidance task (long-term memory). Conversely, the NMDA receptor antagonist alone
      or in combination with diphenylhydantoin, produced significant mnemonic deficits.
      The results indicate that AMPA/kainate receptor antagonists might be of
      importance as adjuvant antiepileptic drugs in patients treated with valproate. A
      possible use of NMDA receptor antagonists may be questionable.

PMID- 11226814
TI  - No change in striatal dopamine re-uptake site density in psychotropic drug naive
      and in currently treated Tourette's disorder patients: a [(123)I]-beta-CIT SPECt
      study.
AB  - BACKGROUND: There is evidence that Tourette's disorder (TD) is associated with
      abnormalities in the dopaminergic system involving the dopamine transporter
      (DAT). Data from [(123)I]-beta-CIT single photon emission computed tomography
      (SPECT) studies and postmortem findings concerning DAT densities in TD patients
      are not conclusive. The objective of our study was to measure DAT densities with
      [(123)I]-beta-CIT binding in TD patients who were either psychotropic drug naive
      or currently treated with antipsychotics (AP) and healthy controls. METHOD:
      Altogether 20 TD patients were investigated. A total of 15 patients were
      psychotropic drug naive and five were currently treated with AP. Ten psychotropic
      drug naive patients were compared with ten age and sex matched healthy subjects.
      Five currently treated patients were compared with five age and sex matched
      psychotropic drug naive TD patients. The investigation was carried out using
      [(123)I]-beta-CIT (2-beta-carbomethoxy-3-beta(4-iodophenyl)-tropane and SPECT.
      Regions of interest (ROI) were drawn over the striatum and the cerebellum.
      RESULTS: The DAT densities measured by the striatal/cerebellar (S/C) binding
      ratio did not differ between drug naive TD patients and the controls. The
      difference between currently AP treated and psychotropic drug naive TD patients
      did not reach the level of significance. There was no correlation between the
      ratio and severity of tics and illness. CONCLUSION: Our study with psychotropic
      drug naive TD patients contributed to clarify the inconsistent results concerning
      the DAT.

PMID- 11226815
TI  - In vitro metabolism of citalopram by monoamine oxidase B in human blood.
AB  - The metabolism of the antidepressant citalopram (CIT) by monoamine oxidase B (MAO
      B) was studied in vitro. In incubations with blood of nine healthy volunteers R
      (P=0.015) and S-(P=0.0034) CIT propionic acid (CITPROP) production was correlated
      with the number of platelets. S-CITPROP production was 5.6 times higher than R
      CITPROP production and in incubations containing the MAO-B inhibitor deprenyl,
      racemic CITPROP production was diminished to 9.1%. To our knowledge, this is the
      first time that MAO-B activity in blood is shown with an antidepressant as
      substrate. As MAO is strongly expressed in human brain, this observation suggests
      that this enzymatic system may be implicated in drug metabolism in the CNS.

PMID- 11226816
TI  - Factors and strategies for improving buccal absorption of peptides.
AB  - Peptides and polypeptides have important pharmacological properties but only a
      limited number (e.g. insulin, oxytocin, vasopressin) have been exploited as
      therapeutics because of problems related to their delivery. The buccal mucosa
      offers an alternative route to conventional, parenteral administration. Peptides
      are generally not well absorbed through mucosae because of their molecular size,
      hydrophilicity and the low permeability of the membrane. Peptide transport across
      buccal mucosa occurs via passive diffusion and is often accompanied by varying
      degrees of metabolism. This review describes various approaches to improve the
      buccal absorption of peptides including the use of penetration enhancers to
      increase membrane permeability and/or the addition of enzyme inhibitors to
      increase their stability. Other strategies including molecular modification with
      bioreversible chemical groups or specific formulations such as bioadhesive
      delivery systems are also discussed.

PMID- 11226817
TI  - Development and characterization of CyA-loaded poly(lactic acid)-poly(ethylene
      glycol)PEG micro- and nanoparticles. Comparison with conventional PLA particulate
      carriers.
AB  - Cyclosporin A (CyA) loaded poly(lactic acid)-poly(ethylene glycol) (PLA-PEG)
      micro- and nanoparticles have been developed using an emulsion-solvent
      evaporation method. Physico-chemical properties, peptide loading content and in
      vitro release profiles of these novel CyA carriers were compared with those
      corresponding to conventional PLA micro- and nanoparticles. Results obtained
      confirm the previously described disposition of PEG chains on the surface of the
      PLA-PEG formulations. In addition, they revealed the presence of CyA molecules on
      the surface of both PLA and PLA-PEG systems. Further determination of the surface
      chemical composition by electron spectroscopy for chemical analysis (ESCA)
      allowed us to quantify the amount of CyA in the nanospheres' top layers, this
      amount being higher for nanoparticles than for microparticles, and higher for the
      PLA systems than for those based on PLA-PEG. In vitro release experiments
      revealed that PLA-PEG particles provided a more adequate control of CyA release
      than conventional PLA micro- and nanoparticles. Physico-chemical characterization
      of the systems during the release studies showed that the developed PLA and PLA
      PEG micro- and nanoparticles were not degraded, which suggest a diffusion
      mediated release mechanism. Furthermore, we have hypothesized that the
      hydrophilic outer shell of PEG provides a stationary layer for the diffusion of
      CyA.

PMID- 11226818
TI  - Reconstruction of an in vitro cornea and its use for drug permeation studies from
      different formulations containing pilocarpine hydrochloride.
AB  - The aim of the present contribution was to develop a functional three-dimensional
      tissue construct to study ocular permeation of pilocarpine hydrochloride from
      different formulations. The in vitro model was compared to excised bovine cornea.
      Modified Franz cells were used to study the transcorneal permeability. Analysis
      was performed by reversed-phase high-performance liquid chromatography.
      Comparisons of the permeation rates through excised bovine cornea and the in
      vitro model show the same rank order for the different formulations. The
      permeation coefficient, K(P), obtained with the cornea construct, is about 2-4
      fold higher than that from excised bovine cornea. It is possible to reconstruct
      bovine cornea as an organotypic culture and also to use this construct as a
      substitute for excised bovine cornea in drug permeation studies in vitro.

PMID- 11226819
TI  - In-vitro release kinetics of cefadroxil-loaded sodium alginate interpenetrating
      network beads.
AB  - This paper reports the development of new interpenetrating polymeric networks of
      sodium alginate with gelatin or egg albumin cross-linked with a common cross
      linking agent, glutaraldehyde, for the in-vitro release of cefadroxil. The beads
      formed were characterized by Fourier transform infra-red spectroscopy, scanning
      electron microscopy and differential scanning calorimetry. Swelling/drying
      experiments were performed to compute the diffusion coefficients and the
      molecular mass between cross-links of the beads. The release results were
      evaluated using an empirical equation to understand the transport mechanism. The
      extent of cross-linking was studied in terms of the size and release
      characteristics of the beads. The experimental and derived quantities have been
      used to study their dependencies on the nature of the polymeric beads, transport
      mechanism, encapsulation efficiency and drug diffusion, as well as the cross
      linking abilities of the polymers.

PMID- 11226820
TI  - In vitro based index of topical anti-inflammatory activity to compare a series of
      NSAIDs.
AB  - The aim of the present work was to generate an index to predict topical
      efficiency of a series of nonsteroidal anti-inflammatory drugs (NSAIDs):
      indomethacin, diclofenac, ketoprofen, piroxicam, tenoxicam and ketorolac. This
      index took into account both biopharmaceutic and pharmacodynamic aspects. The
      biopharmaceutic aspect, based on the maximal flux (J(m)), was determined
      experimentally from transdermal studies carried out with human skin in previous
      work. The pharmacodynamic aspect, based on the ability to inhibit cyclooxygenase
      2 (COX-2) in vitro, was determined by incubating human dermal fibroblasts in
      culture, pre-treated with phobol-12-myristate-13-acetate (PMA) for 6 h, with 25
      microM [(14)C]-arachidonic acid (AA) in the presence of several drug
      concentrations. The most potent inhibitor of COX-2 activity in induced
      fibroblasts was diclofenac while indomethacin, ketoprofen and ketorolac were
      approximately equipotent. Piroxicam and tenoxicam were inhibitors at higher
      concentrations. Based on the proposed index of the topical anti-inflammatory
      activity (ITAA) diclofenac, ketorolac, ketoprofen and indomethacin exhibited
      acceptable efficiency for external use. However, piroxicam and tenoxicam showed
      the lowest topical anti-inflammatory activity of the series assayed. In
      conclusion, indomethacin ketorolac, ketoprofen and diclofenac have shown good
      intrinsic feasibility for formulation into topical pharmaceutical forms. However,
      for dermatological formulations of oxicams, use of penetration enhancers may be
      unavoidable.

PMID- 11226821
TI  - Study of in vitro and in vivo dissolution of theophylline from film-coated
      pellets.
AB  - Tests were performed on the influence of polymer coating films on the rates and
      the extents of in vitro and in vivo liberation of theophylline from pellets.
      Uncoated and coated pellets were used in the experiments. The coating material
      was Eudragit L; The film thickness was varied. The in vivo liberation of
      theophylline was studied in rabbits. The serum level of the released drug
      measured with a TDX Analyser. No appreciable difference was observed between the
      uncoated and the coated pellets as concern the maximum release data, but a
      significant shift was found in t(max) for Eudragit L coated pellets.

PMID- 11226822
TI  - Development and validation of a sensitive analytical method for the simultaneous
      determination of buprenorphine and norbuprenorphine in human plasma.
AB  - A sensitive, specific, and robust capillary gas chromatography-mass spectrometry
      method has been developed and validated for simultaneous determination of
      buprenorphine and its active metabolite, norbuprenorphine, in human plasma.
      Sample preparation involved a clean-up procedure using a Bond Elut Certify
      cartridge followed by derivatization with pentafluoropropionic anhydride.
      Separation was carried out on a HP-1 fused silica capillary column using helium
      as the carrier gas. Selected ion monitoring was used in the electron impact mode.
      Excellent linearity was found between 0.10 and 20.0 ng/ml with a limit of
      quantitation of 0.05 and 0.10 ng/ml for buprenorphine and norbuprenorphine,
      respectively. Interday and intraday assay precisions (%CV) and accuracies were
      within 15.0% for buprenorphine and norbuprenorphine, respectively. Recoveries
      were quantitative and concentration-independent. This method will be applied to
      pharmacokinetic/pharmacodynamic/bioequivalence studies of buprenorphine in
      humans.

PMID- 11226823
TI  - Bioequivalence evaluation of lansoprazole 30-mg capsules (Lanfast and Lanzor) in
      healthy volunteers.
AB  - The bioequivalence of two lansoprazole 30-mg capsules was determined in healthy
      human, adult volunteers after a single dose in a randomized cross-over study. The
      study was conducted at Pharmaconsult, Flemington Pharmaceutical Corp., New
      Jersey, USA. Reference (Lanzor, Laboratoires Houde, Paris, France) and test
      (Lanfast, Julphar, UAE) were administered to volunteers with 240 ml water after
      overnight fasting. Blood samples were collected at specified time intervals,
      plasma was separated and analyzed for lansoprazole using a validated HPLC method.
      The pharmacokinetic parameters AUC(0-t), AUC(0-~), C(max), T(max), T(1/2) and
      elimination rate constant were determined from plasma concentration-time profile
      of both formulations and found to be in good agreement with previously reported
      values. The calculated pharmacokinetic parameters were compared statistically to
      evaluate bioequivalence between the two brands, using the statistical modules
      recommended by the Food and Drug Administration. The analysis of variance (ANOVA)
      did not show any significant difference between the two formulations and 90%
      confidence intervals fell within the acceptable range (80-120%) for
      bioequivalence. Based on these statistical inferences it was concluded that the
      two formulations exhibited comparable pharmacokinetic profiles and that Julphar's
      Lanfast is bioequivalent to Lanzor of Lab. Houde.

PMID- 11226824
TI  - The use of election paramagnetic resonance spectroscopy in early preformulation
      experiments: the impact of different experimental formulations on the release of
      a lipophilic spin probe into gastric juice.
AB  - The lipophilic spin probe TEMPOL-benzoate was dissolved in different experimental
      formulations, including polyethylene glycol 400 (PEG 400), Miglyol, glycerol
      monooleate (GMO), and Cremophor RH-40. Samples were measured by electron
      paramagnetic resonance (EPR) spectroscopy before and after addition to human
      gastric juice. The distance between the first and the third peak in the EPR
      spectrum (2a(N)) was measured to monitor the polarity of the spin probe's
      microenvironment. Moreover, the ratio between the signal amplitudes of the second
      and the third peak (a/b ratio) was used to monitor the mobility of the spin probe
      in a certain formulation. Thus, by calculating 2a(N) and the a/b ratio of the EPR
      spectra it was possible to determine a potential release of the spin probe from
      different formulations into gastric juice. It was found that oily and surface
      active vehicles (Miglyol, Cremophor RH-40, and GMO) were more suitable to protect
      a lipophilic compound from being released within a gastric environment than PEG
      400. Our results demonstrate that EPR spectroscopy seems to be a promising tool
      in early preformulation experiments to monitor the release of spin probes from
      formulations of different nature. This kind of experiment can be of value for the
      optimization of exploratory formulations.

PMID- 11226825
TI  - The delayed induction of c-jun in apoptotic human leukemic lymphoblasts is
      primarily transcriptional.
AB  - Because of their ability to induce lymphoid cell apoptosis, glucocorticoids have
      been used for decades to treat certain human leukemias and lymphomas. Studies
      presented in this paper complement our previous work demonstrating that sustained
      induction of the proto-oncogene c-jun plays a crucial role in the glucocorticoid
      induced apoptotic pathway in CEM cells, human leukemic lymphoblasts. Results from
      measurements of c-jun mRNA half-life with RNase protection assays and of
      transcription by nuclear run-on assays indicate that, in the dexamethasone
      sensitive cloned CEM-C7 cells, c-jun is induced at the transcriptional level.
      Consideration of time-course, however, suggested that this might be a secondary
      or possibly a delayed primary response. Use of cycloheximide to block protein
      synthesis strongly induced c-jun mRNA, suggesting that there had been relief from
      a labile protein repressor of transcription. Comparing the level of induction by
      cycloheximide with that of dexamethasone indicated that the two did not induce by
      an identical mechanism. The high induction by cycloheximide obscured simple
      interpretation of elevated c-jun mRNA levels after concomitant administration of
      cycloheximide and dexamethasone. This was resolved by nuclear run-on experiments,
      which showed that the dexamethasone induction of c-jun mRNA in this system does
      require protein synthesis.

PMID- 11226826
TI  - Sequence analysis and expression of the P450 aromatase and estrogen receptor
      genes in the Xenopus ovary.
AB  - Recent studies point to a key role for the estrogen synthesizing enzyme P450
      aromatase (P450 arom) in ovary determination in fish, birds and reptiles. It is
      unclear whether estrogen synthesis is important in sex determination of Xenopus
      gonad. To determine whether the aromatase gene is transcribed in the gonads of
      Xenopus tadpoles during the sex determination, we cloned a P450 arom cDNA and
      examined the level of P450 arom and estrogen receptor (ER) gene expression in
      association with estrogen activity. cDNA clones for P450 arom were isolated from
      a Xenopus ovarian cDNA library. There was an open reading frame (ORF) of 1500 bp
      from the ATG start to TAA stop codons encoding 500 predicted amino acids. cDNAs
      for P450 arom have previously been cloned from various vertebrates. The homology
      between the Xenopus P450 aromatase and the human P450 arom was higher. The
      expression of the P450 arom gene was mainly limited to reproductive organs. To
      determine the beginning of estrogen activity in gonads of embryos, expression of
      the aromatase and ER gene was also examined by RQ-RT-PCR. Both Xenopus aromatase
      and ER mRNA was detected at stage 51 in gonads. These observations are consistent
      with estrogens having a key role in ovarian development in various other
      vertebrates.

PMID- 11226827
TI  - Quantification of rainbow trout (Oncorhynchus mykiss) zona radiata and
      vitellogenin mRNA levels using real-time PCR after in vivo treatment with
      estradiol-17 beta or alpha-zearalenol.
AB  - Estrogen receptor-mediated induction of zona radiata (ZR) and vitellogenin (VTG)
      mRNA and protein in rainbow trout (Oncorhynchus mykiss) was compared to assess
      their utility as biomarkers for exposure to estrogenic compounds. Partial
      sequences of rainbow trout ZR and beta-actin were cloned by reverse transcriptase
      polymerase chain reaction (RT-PCR) using degenerate primers based on conserved
      regions across a number of species. A 549 bp fragment of the rainbow trout ZR
      gene showed a high degree of amino acid sequence identity to that of salmon
      (77%), winter flounder (64%), carp ZP2 (63%) and medaka (61%) ZR-proteins. The
      1020 bp beta-actin fragment was approximately 100% identical to sequences from
      several species. Real-time PCR was used to quantify the induction of ZR-gene and
      VTG in rainbow trout liver after in vivo exposure to estradiol-17 beta (E(2))
      (0.01, 0.1, 1.0 or 10 mg/kg body weight (bw) fish) or alpha-zearalenol (alpha
      ZEA) (0.1, 1.0 or 10 mg/kg bw). Real-time PCR and indirect enzyme-linked
      immunosorbent assay (ELISA) showed that ZR and VTG were induced in both the liver
      and the plasma after a single injection of E(2) or alpha-ZEA. ZR was more
      responsive to low levels of E(2) and alpha-ZEA than VTG, and real-time PCR was
      shown to be more sensitive than the ELISA. Rainbow trout ZR-gene and proteins
      provide a sensitive biomarker for assessing estrogenic activity.

PMID- 11226828
TI  - Modulation of estrogen receptor gene transcription in breast cancer cells by
      liposome delivered decoy molecules.
AB  - It is well known that breast carcinomas without estrogen receptor (ER) have a
      poor prognosis and do not respond to antiestrogenic therapy. In analyzing the
      question of the lack of ER gene expression, we have considered the possibility to
      modify the ER gene expression by transfecting ER-negative breast cancer cells
      with a polymerase chain reaction product mimicking a putative negative regulatory
      region (--3258/--3157) inside the P3 ER gene promoter. Here we have demonstrated
      the efficacy of the selected sequence used as a decoy molecule in restoring the
      ER gene transcription. When this DNA was complexed and delivered by cationic
      liposomes (PC:DOTAP) a significant increase in the decoy effect was obtained.
      Breast cancer cells receiving the combination treatment responded substantially
      better to reactivation of quiescent ER gene than cells that had received DNA with
      calcium phosphate. This information may be useful for a series of in vitro
      transfections and also for in vivo application of the decoy strategy that is a
      potential therapeutic tool to control disease-related genes such as ER gene in
      breast cancer.

PMID- 11226829
TI  - Electrostatic interactions of androgens and progesterone derivatives with rainbow
      trout estrogen receptor.
AB  - In primary cultures of immature male rainbow trout (rt) hepatocytes, vitellogenin
      (Vg) gene expression is regulated by E(2) via the estrogen receptor (ER).
      However, steroids other than estrogens can also stimulate Vg gene expression.
      These steroids are hardly converted into E(2) during incubation and their
      stimulatory activity is completely inhibited by tamoxifen implying rtER
      involvement. These steroids have no or a slightly positive charge on the Connolly
      surface. In contrast, steroids that failed to stimulate Vg gene expression had a
      strong positive or negative charge around rings C and D due to polarization. The
      amino acid sequences of the ligand binding domains (LBD) of rtER and human ER
      alpha have 57.7% homology; only one amino acid differs in the presumed steroid
      binding site. We modeled the three-dimensional structure of the LBD of rtER using
      X-ray crystallographic data for hER alpha in order to investigate the fit
      (structural and electrostatic) between steroid and rtER. Two factors are
      essential for binding to rtER: (i) hydroxyl or carbonyl groups near C3 and C17 of
      the steroids (hydrophilic regions) that can form hydrogen bonds with His(489),
      Arg(359), and Glu(318), (ii) a hydrophobic steroid nucleus that interacts with a
      hydrophobic region of the rtER LBD through van der Waals forces. If polar
      functional groups are present, the hydrophobic interaction between steroid and
      the rtER LBD is considerably weakened.

PMID- 11226830
TI  - The sex steroid binding protein (SBP or SHBG) of human plasma: identification of
      Tyr-57 and Met-107 in the steroid binding site.
AB  - Tyrosine-57 (Y57) and methionine-107 (M107) have been identified in the binding
      site of the sex steroid binding protein (SBP) (or sex hormone binding globulin)
      of human plasma by replacing the two amino acids with a number of residues of
      varying structure. Replacement of Y57 with phenylalanine resulted in a fourfold
      increase in the K(d) of 5 alpha-dihydrotestosterone but left the K(d) of 17 beta
      estradiol unchanged. Except in two cases, no further loss in binding took place
      when replacing Y57 with other residues, suggesting that the phenolic group of Y57
      may form a hydrogen bond with the ligand. Replacement of M107 with isoleucine
      increased the 5 alpha-dihydrotestosterone K(d) fourfold to a value equal to that
      of rabbit SBP, which contains isoleucine at the corresponding position; however,
      the K(d) of 17 beta-estradiol remained unchanged. Replacement of M107 with
      threonine resulted in a tenfold decrease in 5 alpha-dihydrotestosterone binding
      affinity, whereas replacement with leucine left the K(d) unchanged. These data
      indicate that substitutions on the beta-carbon of the amino acid side-chain at
      position 107 causes significant loss of binding affinity but, as in the case of
      Y57, the activity was not totally eliminated. We conclude that Y57 and M107 form
      part of a structural motif within the steroid binding site and specifically
      contribute binding energy to ring A of 5 alpha-dihydrotestosterone but not to
      ring A of 17 beta-estradiol. We also propose that the integrated contribution of
      several side chains may be required to optimize the ligand affinity of the
      steroid binding site. This proposal may fit a 'lock and key' model where little
      movement of the side chains occurs during binding as might be expected for a
      rigid structure like the steroid nucleus.

PMID- 11226831
TI  - Glycosylation of the murine estrogen receptor-alpha.
AB  - O-linked N-acetylglucosamine (O-GlcNAc) is a highly dynamic and abundant
      modification found on nuclear and cytoplasmic proteins of nearly all eukaryotes.
      O-GlcNAc addition is required for life at the single cell level and is analogous
      to protein phosphorylation in most respects. In a previous study (M.S. Jiang,
      G.W. Hart, A subpopulation of estrogen receptors are modified by O-linked N
      acetylglucosamine. J. Biol. Chem. 270 (1997) 2421-2428), we demonstrated that a
      subpopulation of the murine estrogen receptor-alpha (mER-alpha) is modified by O
      GlcNAc at Thr(575). Here we mutated mER-alpha to convert Thr(575) and Ser(576) to
      Val and Ala, respectively. Surprisingly, this glycosylation-site mutant is still
      extensively modified by O-GlcNAc. Analyses of glycopeptides identified two
      additional sites of modification on mER-alpha, at Ser(10) and Thr(50) near the N
      terminus. The major glycosylation sites are within or near PEST regions,
      suggesting that O-GlcNAc may regulate mER-alpha turnover.

PMID- 11226832
TI  - DHEA inhibits cell growth and induces apoptosis in BV-2 cells and the effects are
      inversely associated with glucose concentration in the medium.
AB  - Dehydroepiandrosterone (DHEA), a major steroid secreted by the adrenal gland
      which decreases with age after adolescence, is available as a nutritional
      supplement. DHEA is known to have antiproliferative effects but the mechanism is
      unclear. In this study using BV-2 cells, a murine microglial cell line, we
      investigated the effect of DHEA on cell viability and the interaction between
      DHEA and glucose concentrations in the medium. We showed that DHEA inhibited cell
      viability and G6PD activity in a dose-dependent manner and that the effect of
      DHEA on cell viability was inversely associated with glucose concentrations in
      the medium, i.e. lowered glucose strongly enhanced the inhibition of cell
      viability by DHEA. DHEA inhibited cell growth by causing cell cycle arrest
      primarily in the G0--G1 phase, and the effect was more pronounced at zero glucose
      (no glucose added, G0) than high glucose (4.5 mg/ml of the medium, G4.5). Glucose
      deprivation also enhanced apoptosis induced by DHEA. At G4.5, DHEA did not induce
      formation of DNA ladder until it reached 200 microM. However, at G0, 100 microM
      DHEA was able to induce apoptosis, as evidenced by the formation of DNA ladder,
      elevation of histone-associated DNA fragmentation and increase in cells
      positively stained with annexin V-FITC and annexin V-FITC/propidium iodide. The
      interactions between DHEA and glucose support the contention that DHEA exerts its
      antiproliferative effects through alteration of glucose metabolism, possibly by
      inhibition of G6PD activity leading to decreased supply of ribose-5-phosphate for
      synthesis of DNA and RNA. Although DHEA is only antiproliferative at
      pharmacological levels, our results indicate that its antiproliferative effect
      can be enhanced by limiting the supply of glucose such as by energy restriction.
      In addition, the present study shows that glucose concentration is an important
      factor to consider when studying the antiproliferative and toxicological effects
      of DHEA.

PMID- 11226833
TI  - Interactions between human plasma sex hormone-binding globulin and xenobiotic
      ligands.
AB  - Human sex hormone-binding globulin (SHBG) binds sex steroids with high affinity.
      In plasma, the number of SHBG steroid-binding sites far exceeds the molar
      concentrations of sex steroids, and will accommodate other ligands such as
      phytoestrogens and fatty acids. We have therefore developed a screening assay to
      identify ligands for SHBG, which exist in our diet or environment. This assay
      allows the binding of potential ligands to SHBG to be assessed under
      physiological conditions, and is sensitive to the effects of plasma constituents.
      Several classes of endocrine active compounds were tested, including hydroxy
      polychlorinated biphenyls (HO-PCBs), phthalate esters, monoesters, chlorinated
      pesticides, as well as synthetic estrogens and phytoestrogens. The relative
      binding affinities (RBAs) of various compounds to SHBG were determined in
      competitive displacement assays, by comparison with 17 beta-estradiol (RBA=100).
      Synthetic estrogens bound SHBG with RBAs of 0.4 (ethinylestradiol)-0.2
      (diethylstilbestrol), while some phytoestrogens bound with RBAs of 0.12
      (coumestrol)-0.04 (naringenin). Many compounds did not bind to SHBG with
      sufficient affinity to allow RBA measurements, and these include: several
      phytoestrogens, such as genistein and kaempferol, polychlorinated biphenyls,
      phthalate esters and monoesters. Of nine HO-PCB congeners tested only 4-OH-2',
      3', 4', 5'-tetraCB and 4-OH-2, 2', 3', 4', 5'-pentaCB bound SHBG in undiluted
      serum with RBAs of 0.05 and 0.11. Although all test compounds bound to SHBG with
      much lower affinity than endogenous sex steroids, these interactions may be
      physiologically relevant in situations where plasma SHBG levels are high and
      endogenous sex steroid levels are low, such as in pre-pubertal children and women
      taking oral contraceptives.

PMID- 11226834
TI  - Pathways of dehydroepiandrosterone formation in rat brain glia.
AB  - In peripheral steroidogenic tissues, dehydroepiandrosterone (D) is formed from
      pregnenolone (P) by the microsomal cytochrome P450c17 enzyme. Although some
      steroidogenic P450s have been found in brain tissue, no enzyme has been shown to
      possess P450c17 activity. We recently demonstrated the presence of an
      alternative, Fe(2+)-dependent pathway responsible for D formation from
      alternative precursors in rat glioma cells. We and others could not find P450c17
      mRNA and protein in rat brain, but demonstrate herein the presence of Fe(2+)
      dependent alternative pathway for D formation in rat brain cortex microsomes.
      Using primary cultures of differentiating rat glial cells, we observed that
      P450c17 mRNA and protein were present in O-2A oligodendrocyte precursors and
      mature oligodendrocytes. In the presence of P, O-2A and mature oligodendrocytes
      formed D. Addition of Fe(2+) together with submaximal concentrations of P
      increased D formation by these cells. Treatment of oligodendrocytes with the
      P450c17 inhibitor SU 10603 in the presence or absence of P failed to inhibit D
      production. These data suggest that D formation in oligodendrocytes occurs
      independently of the P450c17 protein present in the cells. In isolated type I
      astrocytes we did not find neither P450c17 mRNA nor protein. These cells
      responded to Fe(2+) by producing D and addition of P together with Fe(2+) further
      increased D synthesis. SU 10603 failed to inhibit D formation by astrocytes.
      Taken together these results suggest that in differentiating rat brain
      oligodendrocytes and astrocytes D is formed via a P450c17-independent and
      oxidative stress-dependent alternative pathway.

PMID- 11226835
TI  - Transformation of steroids by Bacillus strains isolated from the foregut of water
      beetles (Coleoptera: Dytiscidae): II. Metabolism of 3 beta-hydroxypregn-5-en-20
      one (pregnenolone).
AB  - The in vitro metabolism of pregnenolone by two Bacillus strains (HA-V6-3 and HA
      V6-11) isolated from the foregut of the water beetle Agabus affinis (Payk.) was
      examined in the course of our studies about a possible participation of gut micro
      organisms in the biosynthesis of prothoracic defensive steroids of dytiscids. The
      transformation products were identified by EI GC--MS of culture extracts after
      derivatization. The dominating reactions were hydroxylations, with 7 alpha
      hydroxypregnenolone as the major product. With considerably lower yields, 7 beta-
      and 15xi-hydroxypregenolone were formed by both strains, while 11, 17 and 16
      alpha-hydroxypregnenolone were produced only by HA-V6-3. The occurrence of 7, 11
      alpha- and 7 beta, 11 alpha-dihydroxypregnenolone as well as several minor
      products containing a 17 alpha-OH group proved the capability of HA-V6-11 to
      hydroxylate pregenenolone at C(11) and C(17) as well. The monohydroxylated 7-OH
      pregnenolones were partly oxidized to 7-oxopregnenolone by both strains. In trace
      amounts, HA-V6-3 performed 3 beta-acetylation of pregnenolone.

PMID- 11226836
TI  - Genistein and daidzein modulate in vitro rat uterine contractile activity.
AB  - The present study investigated the effect of genistein, daidzein and estradiol on
      in vitro rat uterine responsiveness to oxytocin (OT) and PGF(2)alpha or
      luprostiol (L). In a first experiment, animals were either sham-operated (SH;
      n=5), or ovariectomized (OVX; n=20) and orally treated for three months with
      either genistein (G; n=5; 10 microg/g BW/d) or daidzein (D; n=5; 10 microg/g
      BW/d) or 17 alpha-ethinylestradiol (E; n=5; 23 microg/kg BW/d) or untreated (OVX;
      n=5). At necropsy, the basal uterine tension was lower in OVX, G and D than in
      SH, the highest value being measured in E. Oxytocin (10(-12); 10(-11) M) or
      PGF(2)alpha (10(-12); 10(-9) M) induced an increase in SH, but not in OVX, E and
      G. In D, only the highest doses were efficient. In a second experiment, 20 intact
      animals were s.c. injected with either genistein (G; n=5; 10 microg/g BW) or
      daidzein (D; n=5; 10 microg/g BW) or estradiol benzoate (E; n=5; 23 microg/kg BW)
      or vehicle (C: controls; n=5), and killed 24 h later. In C and E, OT (10(-15) to
      10(-10) M) or L (10(-12) to 10(-7) M) stimulated uterine contractile activity in
      a dose-dependent manner until a maximal level. On the opposite, in G and D,
      contractile agents (except the highest luprostiol doses) did not stimulate
      myometrium contractions. Moreover, radioligand binding assays showed that
      genistein or daidzein inhibited the specific binding of [(3)H] estradiol to the
      calf uterus estrogen receptor (ER). Therefore, it could be postulated that both
      genistein and daidzein might bind to the rat uterus ER, inducing either anti
      estrogenic or very weak estrogenic effects (depending on the experimental
      conditions) on in vitro uterine responsiveness to OT and PGF(2)alpha or
      luprostiol.

PMID- 11226837
TI  - Whose manuscript is it, anyway?

PMID- 11226838
TI  - The Second Chance Club: repeat adolescent pregnancy prevention with a school
      based intervention.
AB  - The Second Chance Club, a high school-based intervention for pregnant and
      parenting adolescents, was evaluated to determine the repeat birth rate among
      participants. A retrospective case-controlled cohort study was conducted
      (participants, n = 50; control subjects, n = 255) over 3 years after enrollment
      in the intervention. Repeat births occurred in 3/50 (6%) of participants and
      95/255 (37%) of controls (p <.05).

PMID- 11226839
TI  - Inhalant abuse by adolescents.
AB  - The deliberate misuse of volatile substances poses a poorly recognized risk for
      considerable morbidity and mortality in adolescent populations worldwide. The
      abuse of inhalants continues to be a significant problem among our country's
      youth. While many household and industrial chemicals can be inhaled, glues,
      paints, and aerosol propellants are among the most commonly abused. Adolescents
      are often unaware of the health threats posed by inhalation of solvents.
      Inhalation can result in serious organ system dysfunction or even sudden death.
      This review discusses the prevalence of inhalant abuse in the United States,
      summarizes the various types of substances used, highlights the major physiologic
      effects of inhalants, and briefly discusses associated risk behaviors, prevention
      and medical management.

PMID- 11226840
TI  - Adolescent substance use and sexual risk-taking behavior.
AB  - PURPOSE: To examine the relationship of adolescent substance use and dependence
      to sexual risk-taking behavior in late adolescence and young adulthood. METHODS:
      We prospectively examined self-reported sexual behaviors and substance
      involvement questionnaires in a sample of youth in substance abuse treatment
      programs and a comparison sample of sociodemographically similar community youths
      without histories of substance use disorders recruited from media ads.
      Assessments of sexual behaviors and substance involvement (78% white, 51% female)
      were collected at 2, 4, and 6 years after initial assessments, as they
      transitioned from middle adolescence to young adulthood (from age 15.5 to age
      21.5 years, on average). The two samples were compared using Chi-square, analysis
      of variance, and multivariate analysis of variance approaches. Continuous
      indicators of high-risk sexual behaviors and substance involvement were analyzed
      with multiple regression. RESULTS: Earlier age of onset to sexual activity, more
      sexual partners, less consistent use of condoms, more sexually transmitted
      diseases (STDs), and greater prevalence of human immunodeficiency virus testing
      were reported by youth in the clinical treatment sample relative to
      sociodemographically comparable nonabusing community youth. High rates of STDs
      were found among females, and more substance-abusing females reported pregnancies
      than community females. Substance involvement continued to be associated with
      high-risk sexual behavior throughout the transition into young adulthood.
      CONCLUSIONS: Youth identified with substance problems are more likely to engage
      in risky sexual behaviors during adolescence and to continue risky sexual
      behaviors to the extent that substance problems persist. Risk reduction education
      should be included with adolescent substance abuse treatment.

PMID- 11226842
TI  - Racial differences in accuracy of self-assessment of sexual maturation among
      young black and white girls.
AB  - PURPOSE: To examine the validity of maturation self-assessments and to
      investigate the association between race and validity of self-assessments among
      young black and white girls. METHODS: Self-assessments and examiner-assessments
      of areolar and pubic hair development using line drawings were compared at three
      visits among a cohort of 11- to 14-year-old girls enrolled in the National Heart,
      Lung, and Blood Institute's Growth and Health Study. Accuracy rates and kappa
      coefficients were calculated to measure the agreement between girls and
      examiners. Logistic regression models were used to assess the racial differences
      in the accuracy of self-assessments while adjusting for possible confounders.
      RESULTS: Fair to moderate agreement was found between self- and examiner
      assessments (areolar self-assessments: adjusted accuracy rates: 60.7-69.9%,
      kappa: 0.32-0.51; pubic hair self-assessments: adjusted accuracy rates: 57.9
      70.7%, kappa: 0.36-0.55). While there were indications of racial differences in
      the ability to perform self-assessment with black girls tending to self-assess
      less accurately, most of the differences disappeared after adjusting for nurse
      assessed stage. CONCLUSIONS: These findings suggest that self-assessment can
      substitute for examiner evaluations only when crude estimates of maturation are
      needed. However, when accurate maturation stage data are required, examiner
      assessments are necessary. Because black girls are usually more pubertally
      advanced and tend to underestimate their development, the value of self
      assessment is questionable for assessing populations with young black and white
      girls. Use of self-assessment might present biased estimates of maturation and
      confound research findings.

PMID- 11226841
TI  - Screening for sexually transmitted infections among economically disadvantaged
      youth in a national job training program.
AB  - PURPOSE: To evaluate results of screening for syphilis, gonorrhea, and chlamydia
      among youth in a federally funded job training program. METHODS: Data were
      evaluated from medical records of 12,881 randomly selected students in 54 U.S.
      job training centers during 1996. The intake medical evaluation includes
      serologic testing for syphilis. The policy was for females to receive a pelvic
      examination with gonorrhea and chlamydia testing and for males to be first
      screened with a urine leukocyte esterase (LE) assay, with follow-up gonorrhea and
      chlamydia testing for those with positive LE results. RESULTS: Adjusting for our
      sampling strategy, among females, an estimated 9.2% had a positive chlamydia
      test, 2.7% a positive gonorrhea test, and 0.4% had a positive syphilis test.
      Gonorrhea and chlamydia rates among females were highest in African-American
      followed by Native American students. Chlamydia infection was most common in
      younger women < or = 17 years of age. An estimated 0.1% of males had a positive
      syphilis test, and 4.8% of males a positive urine LE test. Of 103 LE-positive
      males tested for gonorrhea and chlamydia, only 27 (26%) had a positive test for
      one of these STDs. CONCLUSIONS: Our study supports routine screening of
      adolescents for gonorrhea and chlamydia, including those youth from
      socioeconomically disadvantaged backgrounds. Because individuals from such
      backgrounds may not regularly interact with traditional clinical health care
      systems, screening and treatment should be offered in alternative settings, such
      as the job training program described in this study.

PMID- 11226843
TI  - Barriers to screening sexually active adolescent women for chlamydia: a survey of
      primary care physicians.
AB  - PURPOSE: To determine the proportion of primary care physicians who screen
      sexually active teenage women for chlamydia and to determine demographic factors,
      practice characteristics, and attitudes associated with chlamydia screening.
      METHODS: We obtained a random sample of 1600 Pennsylvania physicians from the
      American Medical Association masterfile, stratified to include at least 40% women
      and equal numbers of family physicians, internists, obstetricians/gynecologists,
      and pediatricians. In January 1998, physicians received mailed questionnaires;
      nonrespondents received two follow-up mailings. Physician characteristics
      associated with chlamydia screening were determined using bivariate and logistic
      regression analyses. RESULTS: Only one-third of physicians responded that they
      would screen asymptomatic, sexually active teenage women for chlamydia during a
      routine gynecologic examination. In multivariate analysis, physicians were
      significantly (p <.05) more likely to screen if they were female (43% vs. 24%),
      worked in a clinic versus solo practice (60% vs. 18%), worked in a metropolitan
      location (46% vs. 26%), or had a patient population > or = 20% African-American
      (54% vs. 25%). Attitudes associated with screening included the belief that most
      18-year-old women in their practice were sexually active (36% vs. 12%), feeling
      responsible for providing information about the prevention of sexually
      transmitted diseases to their patients (42% vs. 21%), or knowing that screening
      for chlamydia prevents pelvic inflammatory disease (37% vs. 13%). Physicians were
      less likely to screen if they believed that the prevalence of chlamydia was low
      (10% vs. 41%). CONCLUSIONS: A majority of physicians do not adhere to recommended
      chlamydia screening practices for teenage women. Interventions to improve
      chlamydia screening might target physicians who are male, in private practice, or
      who practice in rural areas, and should focus on increasing awareness of the
      prevalence of chlamydia and benefits of screening.

PMID- 11226844
TI  - Adolescent binge/purge and weight loss behaviors: associations with developmental
      assets.
AB  - PURPOSE: To study associations between binge/purge and weight loss behaviors and
      "developmental assets" among adolescent girls and boys. METHODS: The Search
      Institute's Profile of Student Life: Attitudes and Behaviors self-report
      questionnaire was administered to 48,264 girls and 47,131 boys in grades 6
      through 12 at schools in 213 cities or towns across the United States. The 156
      item questionnaire measured 40 "developmental assets," or protective factors
      associated with successful adolescent development. Developmental assets were
      examined using multiple logistic regression among students who reported
      binge/purge behaviors, weight loss behavior, both, or neither. RESULTS:
      Developmental assets related to positive identity were the strongest
      discriminators of binge/purge and weight loss behaviors in both girls and boys.
      Girls who reported binge/purge and weight loss behaviors were about half as
      likely to report feeling a sense of purpose [odds ratio (OR) = 0.45, 95%
      confidence interval (CI) = 0.40, 0.50] and high self-esteem (OR = 0.55, 95% CI =
      0.49, 0.61), compared with girls not reporting either of these behaviors. Among
      boys the ORs were: sense of purpose OR = 0.53 (95% CI = 0.46, 0.61) and self
      esteem OR = 0.76 (95% CI = 0.65, 0.88). Assets related to values about abstinence
      from alcohol, drugs, or sex ("restraint") were also significant correlates. Girls
      and boys who reported these values were less likely to report binge/purge and
      weight loss behaviors, compared with those who did not report these values
      (girls: OR = 0.56, 95% CI = 0.50, 0.63; boys: OR = 0.83, 95% CI = 0.70, 0.97).
      CONCLUSIONS: Internal assets such as self-esteem, sense of purpose, and values
      related to abstinence from alcohol and sex appear to be protective against
      unhealthy eating behaviors and may reflect a general resilience that buffers
      against a broad range of health risk behaviors.

PMID- 11226845
TI  - Differences between adolescents and young adults at presentation to an eating
      disorders program.
AB  - OBJECTIVE: To describe differences between adolescents and adults in clinical
      presentation of eating disorders. METHODS: Data from the charts of 622 female
      patients treated for an eating disorder in a division of adolescent medicine
      between 1980 and 1994 were coded and computerized. General categories included
      demographic and family factors, weight loss and weight changes, eating-related
      behaviors, diagnosis and severity, and treatment issues. Differences between the
      438 patients who were aged 9-19 years (adolescents) and 184 patients who were
      aged 20-46 years (adults) were analyzed. RESULTS: Adolescents were more likely
      than adults (p <.05) to have a diagnosis of "eating disorder not otherwise
      specified," lower global severity score, greater denial and less desire for help,
      weight loss > or = 3 lb/month, lower original and maximum weights, and history of
      fasting and elimination of junk food from their diets. Adults were more likely
      than adolescents (p <.05) to have >1 year of weight loss, greater total weight
      loss, history of binge eating and laxative use, history of diuretic and ipecac
      use, diagnosis of bulimia nervosa, and prior use of psychiatric medications.
      Adolescents and adults did not differ (p >.05) in parents' occupational level;
      height, weight, and percent ideal body weight at presentation; original percent
      ideal body weight; use of diet pills, elimination of meat and use of a low-fat
      diet; daily calorie intake; prior eating disorder hospitalizations; and
      hospitalization during the course of treatment. CONCLUSIONS: The findings in this
      study document and confirm that there are important differences between
      adolescents and adults that must be taken into account in the evaluation and
      treatment of patients with eating disorders.

PMID- 11226846
TI  - Trends and subgroup differences in transportation-related injury risk and safety
      behaviors among high school students, 1991-1997.
AB  - PURPOSE: To examine national trends in transportation-related injury risk and
      safety behaviors among U.S. high school students. METHODS: To examine secular
      trends in riding with a driver who had been drinking, driving after drinking, and
      using seat belts, bicycle helmets, and motorcycle helmets, we used logistic
      regression to analyze data from national Youth Risk Behavior Surveys (YRBS)
      conducted in 1991, 1993, 1995, and 1997. The YRBS is a self-administered,
      anonymous survey that uses a national probability sample of U.S. students in
      public and private schools from grades 9-12 (N = 55,734 for all years combined).
      RESULTS: The percentages of students who rode with a driver who had been drinking
      (36.6% in 1997), drove after drinking alcohol (16.9% in 1997), always wore seat
      belts (33.2% in 1997), and always wore a motorcycle helmet when riding a
      motorcycle (45.0% in 1997) remained stable between 1991 and 1997. From 1991 to
      1997, the percentage of bicycle riders who always wore a helmet when bicycling
      showed a small but statistically significant increase (1.1% in 1991 to 3.8% in
      1997), but helmet use remained low. CONCLUSION: Many young people place
      themselves at unnecessary risk for motor vehicle- and bicycle-related crash
      injuries and fatalities. Improved motor vehicle- and bicycle-related injury
      prevention strategies are needed that specifically target adolescents.

PMID- 11226847
TI  - Adolescent contraceptive non-use and covariation among risk behaviors.
AB  - PURPOSE: To investigate whether adolescent contraceptive non-use is associated
      with other risk behaviors. METHODS: A multistage sampling procedure produced a
      sample of 913 sexually active high school students. They completed a self
      administered questionnaire that required mainly "yes" or "no" answers to
      questions involving participation in a range of risk behaviors. A series of
      multivariate logistic regression models investigated the relationships between
      contraceptive non-use and selected hypothesised correlates, controlling for key
      demographic variables. RESULTS: Contraceptive non-use was not significantly
      associated with use of cigarettes, alcohol, or inhalants; perpetration or being a
      victim of violence; exposure to risk of physical injury; and suicidality. For
      males only, there was a significant inverse association between contraceptive non
      use and use of cannabis in the previous month. This was not the case for lifetime
      cannabis use for either gender. There was a significant inverse relationship
      between contraceptive non-use and knowing the most recent partner for more than 7
      days, but no association for the number of partners nor duration since the last
      intercourse. For females only, there was a significant inverse association
      between contraceptive non-use and both age and age of first intercourse.
      CONCLUSIONS: This study does not support the hypothesis that contraceptive non
      use is a component of the "risk behavior syndrome." Decisions to participate in
      intercourse and to use contraception have different psychosocial foundations.
      Prevention efforts should prioritize relationships with new partners and younger
      girls who commence intercourse early.

PMID- 11226848
TI  - Adolescent girls' sexual attitudes and opposite-sex relations in 1970 and in
      1996.
AB  - PURPOSE: To describe changes in adolescent girls' sexual attitudes and
      relationships with boys between 1970 and 1996, particularly girls who had early
      onset of sexual intercourse. METHOD AND INSTRUMENT: The study includes two
      cohorts. The first is from the Swedish longitudinal research program, "Individual
      Development and Adaptation." This cohort included all eighth-grade girls (15-year
      olds), 522 girls, in a mid-Swedish community in 1970. In 1996, the same
      instrument (Adjustment Screening Test) was administered to all eighth-grade girls
      (15-year-olds), 567 girls, in the same community. These girls make up the second
      cohort. RESULTS: Girls were thinking and feeling similarly about sexual matters
      in 1970 and 1996. Furthermore, the same factors correlated with early sexual
      onset of intercourse in both cohorts, and the correlations were of about the same
      magnitudes. This suggests that sexuality has quite similar developmental
      implications in the lives of teenaged girls now as it had 25 years ago. There
      were, however, differences in the prevalence of opposite-sex relations. Compared
      with girls in 1970, girls in 1996 had had fewer sexual relationships and had
      postponed their sexual transition. CONCLUSIONS: This study shows that perceptual,
      bodily, and behavioral maturation are positively related to each other. The girls
      with early onset of intercourse matured early both in 1970 and in 1996. They felt
      sexually more experienced than their age-mates, and they also aspired to be
      older.

PMID- 11226849
TI  - Efficacy of interferon-gamma and amphotericin B for the treatment of systemic
      murine histoplasmosis.
AB  - The number of cases of systemic histoplasmosis has increased substantially in
      recent years, and improved therapy is needed. We examined the efficacy of
      immunomodulation with interferon (IFN)-gamma alone or in combination with a
      suboptimal regimen of amphotericin B for the treatment of primary systemic murine
      histoplasmosis. In the first study, BALB/c mice were infected with Histoplasma
      capsulatum G217B and treated with 10(5) U of IFN given every other day either
      preinfection and postinfection or only postinfection, alone or in combination
      with amphotericin B. IFN alone given subcutaneously (s.c.) postinfection
      prolonged survival over untreated controls (P < 0.01), whereas intravenous (i.v.)
      administration was ineffective. All combination regimens and amphotericin B alone
      significantly prolonged survival (P < 0.0001). The combination regimens of
      amphotericin B and IFN i.v. (pre- and postinfection) or IFN s.c. (postinfection)
      reduced the fungal burden in the liver and spleen; the latter regimen had
      superior efficacy in the spleen (P < 0.05) to either amphotericin B or IFN alone.
      After infection with a low-challenge inoculum, IFN given s.c. (pre- and
      postinfection) alone caused a significant reduction in fungal burden in the
      spleen (P < 0.001). In an acutely lethal model, combination regimens of IFN s.c.
      or i.v. and amphotericin B again prolonged survival (P < 0.01-0.001), with
      amphotericin B plus IFN given s.c. (pre- and postinfection) superior to all
      regimens (P < 0.05-0.01). This regimen also showed enhanced efficacy in causing
      the reduction of fungal burden in the spleen (P < 0.05). These results indicate
      that IFN in combination with AmB shows enhanced efficacy in the treatment of
      systemic histoplasmosis and support the potential utility of IFN as an adjunctive
      therapy.

PMID- 11226850
TI  - Orientia tsutsugamushi infection: overview and immune responses.
AB  - Orientia tsutsugamushi, an obligate intracellular bacterium, was isolated for the
      first time in 1930. Infections by virulent strains are characterized by fever,
      rash, eschar, pneumonia, myocarditis, and disseminated intravascular coagulation.
      Here we review the general aspects of O. tsutsugamushi and immune responses in
      terms of inflammation, protective immune mechanisms, and immunogenic antigens.

PMID- 11226851
TI  - Pseudomonas aeruginosa and the in vitro and in vivo biofilm mode of growth.
AB  - The biofilm mode of growth is the survival strategy of environmental bacteria
      like Pseudomonas aeruginosa. Such P. aeruginosa biofilms also occur in the lungs
      of chronically infected cystic fibrosis patients, where they protect the bacteria
      against antibiotics and the immune response. The lung tissue damage is due to
      immune complex mediated chronic inflammation dominated by polymorphonuclear
      leukocytes releasing proteases and oxygen radicals.

PMID- 11226852
TI  - Cellular and molecular mechanisms of internalization of mycobacteria by host
      cells.
AB  - Mycobacteria are intracellular pathogens capable of invading mononuclear
      phagocytes, mucosal epithelial cells (including M cells) and Schwann cells. To
      enter cells, mycobacteria have been shown to interact with several molecules on
      macrophage and epithelial cell surfaces. This suggests adaptation to the host
      environment. In this review we address the strategies used by pathogenic
      mycobacteria to gain access to the intracellular environment.

PMID- 11226853
TI  - Immunity and protection against Brucella abortus.
AB  - Brucella abortus is an intracellular pathogen that causes disease in cattle and
      in humans. The response against B. abortus involves the whole gamut of the immune
      system, from innate to adaptive immunity resulting from stimulation of antigen
      presenting cells, NK cells, CD4(+) and CD8(+) T cells, and B cells.

PMID- 11226854
TI  - Modulation of host responses to blood-stage malaria by interleukin-12: from
      therapy to adjuvant activity.
AB  - This review focuses on the role of interleukin (IL)-12, a proinflammatory
      cytokine with pleiotropic effects as a potent immunoregulatory molecule and
      hematopoietic growth factor, in infection with Plasmodium parasites, the
      causative agents of malaria. IL-12 has been demonstrated to have profound effects
      on the immune response to blood-stage malaria, to induce protection, and to
      alleviate malarial anemia. In combination with an anti-malarial drug, IL-12 is
      effective in an established malaria infection. This cytokine also has potent
      immune effects as a malaria vaccine adjuvant. However, IL-12 can also mediate
      pathology during blood-stage malaria.

PMID- 11226855
TI  - Evolutionary trends in the genus Bordetella.
AB  - The genus Bordetella comprises seven species with pathogenic potential for
      different host organisms. This article attempts to review our current knowledge
      about the systematics and evolution of this important group of pathogens, their
      relationship to environmental microorganisms and about molecular mechanisms of
      host adaptation.

PMID- 11226856
TI  - The potential use of plant pathogens against crops.
AB  - This paper illustrates the characteristics of plant pathogens that have been
      found to be of most relevance in offensive biological warfare programmes. It
      shows how states envisaged these pathogens might be used against crops. It
      assesses whether the Biological and Toxin Weapons Convention can deal adequately
      with this potential threat.

PMID- 11226857
TI  - The 1918 Spanish influenza: integrating history and biology.
AB  - In 1918 an influenza pandemic killed 40 million people. It is now possible to
      study the genetic features of the 1918 virus. Such analyses will try to answer
      questions about the origin and the unusual virulence of this pandemic virus.

PMID- 11226858
TI  - Automatic continuous positive airway pressure devices for the treatment of sleep
      apnea hypopnea syndrome.

PMID- 11226859
TI  - Sleep disorders in the elderly.
AB  - Sleep disorders and sleeping difficulty are among the most pervasive and poorly
      addressed problems of aging. As the population ages, a burgeoning cadre of
      seniors will seek attention for sleeping difficulties and sleep disorders. Sleep
      changes with age, and sleeping problems and disorders generally increase with
      aging. At present, health care professionals are not receiving adequate
      preparation and training to help the elderly cope with age-related sleeping
      problems, and several specific areas are ripe for investigation.

PMID- 11226860
TI  - Prospective randomized comparison of impedance-controlled auto-continuous
      positive airway pressure (APAP(FOT)) with constant CPAP.
AB  - Background: The measurement of impedance permits reliable detection of
      obstructive apneas, hypopneas and upper airways resistance syndrome.Objective: To
      establish whether impedance-controlled self-adjusting positive airway pressure
      therapy (APAP(FOT)) is equally as good as constant continuous positive airway
      pressure (CPAP) in the treatment of sleep apnea syndrome (OSAS).Methods: Twenty
      men and five women with OSAS (age 52.8+/-9.0 years, body mass index (BMI) 31.4+/
      5.0 kg/m(2), AHI 32.2+/-18.1/h (mean+/-SD)) underwent baseline polysomnography,
      manual CPAP titration and two nights of treatment, one with APAP(FOT), one with
      constant CPAP.Results: With both modes, a significant reduction in respiratory
      disturbances was seen (apnea/hypopnea index (AHI) baseline 32.2+/-18.1/h,
      constant CPAP 6.6+/-8.7, APAP(FOT) 5.5+/-3.8/h, P<0.001 baseline vs. each
      treatment mode). Under APAP(FOT), the sleep profile was normalized (S3/4 baseline
      16.3+/-13.9% total sleep time (TST), APAP(FOT) 21.6+/-10.9% TST, P<0.05, rapid
      eye movement (REM) 14.2+/-6.7% TST vs. 20.3+/-7.3% TST, P<0.01), while with
      constant CPAP, a tendency towards improvement was found. The mean treatment
      pressure with APAP(FOT) was significantly lower than the constant CPAP (5.7+/-2.1
      vs. 8.3+/-1.6 mbar, P<0.001).Conclusion: We conclude that APAP(FOT) is at least
      as effective as constant CPAP in normalizing sleep and breathing in OSAS.

PMID- 11226861
TI  - First night effect and reverse first night effect in older adults with primary
      insomnia: does anxiety play a role?
AB  - Objective: The main objective was to examine first night effect (FNE) and reverse
      first night effect (RFNE) in older insomniacs and the role played by anxiety in
      these processes.Background: RFNE has been documented in a middle-aged sample of
      insomniacs, but little research has been done on RFNE or FNE in older insomniacs.
      Also, a relationship between anxiety and FNE has not been established.Methods:
      Participants were 77 older adults with primary insomnia (57 females, 20 males).
      Two consecutive nights of polysomnography (PSG) were conducted, and the state
      form of the State-Trait Anxiety Inventory was completed each night. Sleep diaries
      were completed the morning after each (PSG) and for 2 weeks at home.Results: Most
      participants exhibited a FNE (57%) rather than a RFNE (26%). State anxiety was
      elevated on PSG night 1 relative to PSG night 2 in the FNE group but not the RFNE
      group, and the FNE group reported greater home total sleep time. Among FNE
      participants, self-reported total sleep and sleep efficiency were significantly
      higher on PSG night 2 than at home.Conclusions: Most older insomniacs show a FNE,
      but a portion exhibit a RFNE. Elevated anxiety on PSG night 1 may play a role in
      FNE.

PMID- 11226862
TI  - Initial demonstration of the accuracy and utility of an ambulatory, three
      dimensional body position monitor with normals, sleepwalkers and restless legs
      patients.
AB  - Objective: To evaluate the accuracy and provide a pilot demonstration of the
      clinical utility of the BodyTrac, a new, ambulatory device that identifies body
      position and records and stores this data for a period of over 2
      weeks.Background: Diagnosis and treatment evaluation of behavioral sleep-related
      events (BSREs) that occur with the major parasomnias such as sleepwalking, night
      terrors and REM behavior disorder have been hampered by the problems inherent in
      recording relatively rare events which are mostly not recalled by the patients.
      The number, time of occurrence and pattern of motor behavior for these events
      has, therefore, never been adequately described. Even the amount of nocturnal
      walking associated with the restless legs syndrome (RLS) has been hard to specify
      given the usual problems of night to night variability and in obtaining accurate,
      subjective reports. The newly developed BodyTrac monitor, by recording body
      position once every 30 s during a sleep period, provides an enabling technology
      for evaluating BSREs and may also enhance evaluation of nocturnal waking
      activities of RLS patients.Design and methods: Three test protocols were
      completed: an analog-type laboratory test of the BodyTrac's accuracy, an
      evaluation of seniors with and without sleep disorders, and, finally, evaluation
      of adult sleepwalkers and RLS patients including a full-night sleep lab
      assessment. The last two procedures also included monitoring in the home
      environment.Results and conclusions: The BodyTrac reliably and accurately
      identified both the wearer's body position (93% agreement with observer) and
      BSREs (sensitivity=100%, specificity=94-100%.) Patients were able to wear the
      BodyTrac during sleep in their home environment with minimal discomfort. The
      pilot data here suggest that some sleep walkers may have many small BSREs in
      addition to the larger events that are usually the only ones known to occur.

PMID- 11226863
TI  - Effects of short-term PAP treatment on endurance exercise performance in
      obstructive sleep apnea patients.
AB  - Objective: To measure the effects of 4 weeks of nasal positive airway pressure
      therapy (PAP) on exercise performance in obstructive sleep apnea patients
      (OSA).Background: Little published research is available which describes the
      effects of OSA on exercise tolerance or upon the potential of exercise testing to
      evaluate the outcomes of PAP therapy.Methods: Exercise testing was performed on
      an electronic cycle ergometer with continuous ramping to allow collection of
      numerous data points for each subject, up to a vigorous terminal intensity.
      Linear regression established each subject's pre-treatment scores for the
      dependent variables at 60% of estimated peak power (W(60%)). Responses at the pre
      treatment W(60%) test were used to quantify and compare to responses at the same
      power output after treatment.Results: OSA by nocturnal polysomnography was
      moderately severe in this group; the respiratory distress index was 48+/-22
      (mean+/-SD; n=9). Exercise heart rates after PAP therapy averaged 10.2 bt/min
      less at W(60%) (P<0.05). Other variables were lower but non-significantly so,
      further suggesting a lower cardiorespiratory exercise demand after treatment,
      i.e. oxygen consumption ( downward arrow7.6%), and Rating of Perceived Exertion (
      downward arrow8.8%).Conclusion: Brief treatment with PAP therapy improves
      objective markers of aerobic exercise performance.

PMID- 11226864
TI  - Self-reported levels of sleepiness among subjects with insomnia.
AB  - Objectives: To determine the prevalence of sleepiness in a cohort of insomnia
      subjects. We evaluated if differential levels of subjective sleepiness predict
      systematic differences in the polysomnographic characteristics of these
      subjects.Background: Insomnia is prevalent among the adult population. While it
      has been speculated that sleepiness may be an important daytime consequence of
      insomnia, this has not been demonstrated.Methods: Sixty-two subjects with
      complaints of insomnia for at least 6 months were polysomnographically evaluated.
      Subjects were asked to self-report their level of sleepiness based on their
      experiences for the previous 7 days. Subjects were divided into three groups
      based on their level of sleepiness. Sleepiness was determined using the excessive
      daytime sleepiness scale of the Sleep/Wake Activity Inventory (SWAI-EDS).Results:
      Twenty-two percent of insomnia subjects were found to be sleepy on the EDS scale
      of the SWAI. The level of sleepiness was also found to predict difficulty
      initiating sleep both on the nocturnal scale of the SWAI, and on nocturnal
      polysomnography.Conclusions: This study established a base rate of sleepiness
      among a cohort of insomnia subjects. It also demonstrated a wide spectrum of
      sleepiness/alertness among subjects with insomnia. Differential levels of
      sleepiness were found to predict nocturnal sleep latencies.

PMID- 11226865
TI  - Journal search and commentary.

PMID- 11226866
TI  - Article reviewed: Serum leptin and vascular risk factors in obstructive sleep
      apnea.

PMID- 11226867
TI  - Article reviewed: Case-control study of 24 h ambulatory blood pressure in
      patients with obstructive sleep apnoea and normal matched control subjects.

PMID- 11226868
TI  - Article reviewed: Entrainment of free-running circadian rhythms by melatonin in
      blind people.

PMID- 11226869
TI  - Article reviewed: Restless legs syndrome in monozygotic twins: clinical
      correlates.

PMID- 11226870
TI  - 15th Congress of the European Sleep Research Society, Istanbul, Turkey, September
      12-16, 2000.

PMID- 11226871
TI  - The oligomeric nature of Na/K-transport ATPase.
AB  - Since the discovery of Na/K-ATPase, evidence has accumulated to suggest that 1
      mol of ATP hydrolysis occurs via the Na(+)-occluded ADP-sensitive phosphoenzyme,
      the K(+)-sensitive phosphoenzyme and the K(+)-occluded enzyme accompanying active
      transport of 3Na(+) and 2K(+) according the Post-Albers scheme. However, some
      controversial issues have arisen concerning whether the functional unit of the
      enzyme is an alpha beta-protomer or a much higher oligomer, which would be
      related to the mechanism of transport, either sequential or simultaneous.
      Detailed studies of oligomer interaction and the reactivity of the enzyme and a
      comparison of the extent of phosphorylation with ligand-binding capacities in the
      presence or absence of ATP hydrolysis and others strongly suggest that the
      functional unit of the enzyme in the membrane is a tetraprotomer, (alpha
      beta)(4). They also suggest that each reaction intermediate of the Post-Albers
      scheme, respectively, reflects half of the site property of the intermediate and
      that another half binds ATP. These data may be useful not only to answer the long
      standing question of whether the mechanism functions in the presence of both
      Na(+) and K(+) but also contribute to a better understanding of the mechanism of
      P-type pump ATPase in general.

PMID- 11226872
TI  - The OmpR-family of proteins: insight into the tertiary structure and functions of
      two-component regulator proteins.
AB  - The Escherichia coli DNA-binding protein OmpR is the best characterized of those
      regulator proteins making up "two-component system," the simplest known form of
      bacterial signal transduction systems. Previous inspections of the E. coli genome
      DNA sequences have revealed that there are 15 proteins whose amino acid sequences
      show extensive similarities to that of OmpR (the OmpR-family of proteins). The
      three-dimensional structures of several OmpR-family proteins have been
      determined. In this review, we investigated the structures and amino acid
      sequences of this family of proteins. The results reveal several notable
      conservative varieties in their tertiary structures and functions.

PMID- 11226873
TI  - Characterization of the mac-1 gene encoding a putative ABC transporter from
      Myxococcus xanthus.
AB  - The mac-1 gene of Myxococcus xanthus TA, an antibiotic TA producer, encoded a
      protein with strong sequence similarity to the antibiotic ATP-binding cassette
      (ABC) transporter for macrolide antibiotics. The mac-1 gene encoding protein (Mac
      1) had two ATP-binding domains containing Walker A and B motifs, and no
      hydrophobic transmembrane regions. Insertional inactivation of mac-1 caused
      enhanced sensitivity to oleandomycin, a macrolide antibiotic, while the mac-1
      mutant showed normal export of antibiotic TA into the extracellular fluid. The
      mac-1 mutant could form mounds, but was unable to form fruiting bodies or
      sporulate under nutrient starvation. A primary role for Mac-1 in M. xanthus may
      be as a transporter which exports or imports a molecule required for the
      sporulation process.

PMID- 11226874
TI  - Cloning and expression of the catalase gene from the anaerobic bacterium
      Desulfovibrio vulgaris (Miyazaki F).
AB  - We identified a gene encoding a catalase from the anaerobic bacteria
      Desulfovibrio vulgaris (Miyazaki F), and the expression of its gene in
      Escherichia coli. The 3.3-kbp DNA fragment isolated from D. vulgaris (Miyazaki F)
      by double digestion with EcoRI and SalI was found to produce a protein that binds
      protoheme IX as a prosthetic group in E. coli. This DNA fragment contained a
      putative open reading frame (Kat) and one part of another open reading frame (ORF
      1). The amino acid sequence of the amino terminus of the protein purified from
      the transformed cells was consistent with that deduced from the nucleotide
      sequence of Kat in the cloned fragment of D. vulgaris (Miyazaki F) DNA, which may
      include promoter and regulatory sequences. The nucleotide sequence of Kat
      indicates that the protein is composed of 479 amino acids per monomer. The
      recombinant catalase was found to be active in the decomposition of hydrogen
      peroxide, as are other catalases from aerobic organisms, but its K(m) value was
      much greater. The hydrogen peroxide stress against D. vulgaris (Miyazaki F)
      induced the activity for the decomposition of hydrogen peroxide somewhat, so the
      catalase gene may not work effectively in vivo.

PMID- 11226875
TI  - Two new modes of smooth muscle myosin regulation by the interaction between the
      two regulatory light chains, and by the S2 domain.
AB  - Previous studies indicated that single-headed smooth muscle myosin and S1 (a
      single head fragment) are not regulated through phosphorylation of the regulatory
      light chain (RLC). To investigate the importance of the double-headedness of
      myosin and of the S2 region for the phosphorylation-dependent regulation, we made
      three types of recombinant mutant smooth muscle HMMs with one intact head and an
      N-terminally truncated head. The truncated head of Delta MD lacked the motor
      domain, that of Delta(MD+ELC) lacked the motor and essential light chain binding
      domains, and single-headed HMM had one intact head alone. The basal ATPase
      activities of the three mutants decreased as the KCl concentration became less
      than 0.1 M. Such a decrease was not observed for S1, which had no S2 region,
      suggesting that S2 is necessary for this myosin behavior. This activity decrease
      also disappeared when RLCs of Delta MD and Delta(MD+ELC), but that of single
      headed HMM, were phosphorylated. When their RLCs were unphosphorylated, the three
      mutants exhibited similar actin-activated ATPase levels. However, when they were
      phosphorylated, the actin-activated ATPase activities of Delta MD and
      Delta(MD+ELC) increased to the S1 level, while that of single-headed HMM remained
      unchanged. Even in the phosphorylated state, the actin-activated ATPase
      activities of the three mutants and S1 were much lower than that of wild-type
      HMM. We propose that S2 has an inhibitory function that is canceled by an
      interaction between two phosphorylated RLCs. We also propose that a cooperative
      interaction between two motor domains is required for a higher level of actin
      activation.

PMID- 11226876
TI  - Surface dynamics of bacteriorhodopsin as revealed by (13)C NMR studies on
      [(13)C]Ala-labeled proteins: detection of millisecond or microsecond motions in
      interhelical loops and C-terminal alpha-helix.
AB  - We have recorded (13)C NMR spectra of [2-(13)C]-, [1-(13)C]-, [3-(13)C],- and
      [1,2,3-(13)C(3)]Ala-labeled bacteriorhodopsin (bR), and its mutants, A196G,
      A160G, and A103C, by means of cross polarization-magic angle spinning (CP-MAS)
      and dipolar decoupled-magic angle spinning (DD-MAS) techniques, to reveal the
      conformation and dynamics of bR, with emphasis on the loop and C-terminus
      structures. The (13)C NMR signals of the loop (C-D, E-F, and F-G) regions were
      almost completely suppressed from [2-(13)C]-, [1-(13)C]Ala-, and [1-(13)C]Gly
      labeled bR, due to the presence of conformational fluctuation with correlation
      times of 10(-4) s that interfered with the peak-narrowing by magic angle
      spinning. The observation of such suppressed peaks for specific residues provides
      a unique means of detecting intermediate frequency motions on the time scale of
      ms or micros in the surface loops of membrane proteins. Instead, the three well
      resolved (13)C CP-MAS NMR signals of [2-(13)C]Ala-bR, at 50.38, 49.90, and 47.96
      ppm, were ascribed to the C-terminal alpha-helix previously proposed from the
      data for [3-(13)C]Ala-bR: the former two peaks were assigned to Ala 232 and 238,
      in view of the results of successive proteolysis experiments, while the highest
      field peak was ascribed to Ala 235 prior to Pro 236. Even such (13)C NMR signals
      were substantially broadened when (13)C NMR spectra of fully labeled [1,2,3
      (13)C]Ala-bR were recorded, because the broadening and splitting of peaks due to
      the accelerated transverse relaxation rate caused by the increased number of
      relaxation pathways through a number of (13)C-(13)C homo-nuclear dipolar
      interactions and scalar J couplings, respectively, are dominant among (13)C
      labeled nuclei. In addition, approximate correlation times for local
      conformational fluctuations of different domains, including the C-terminal tail,
      C-terminal alpha-helix, loops, and transmembrane alpha-helices, were estimated by
      measurement of the spin-lattice relaxation times in the laboratory frame and spin
      spin relaxation times under the conditions of cross-polarization-magic angle
      spinning, and comparative study of suppressed specific peaks between the CP-MAS
      and DD-MAS experiments.

PMID- 11226877
TI  - Inhibition of aldosterone production in rat adrenal mitochondria by 18-ethynyl-11
      deoxycorticosterone: a simple model for kinetic interpretation of mechanism-based
      inhibitors.
AB  - A simple mathematical model for studying mechanism-based inhibitors (MBIs) is
      presented. The mathematical equations are deduced for an experimental protocol
      consisting of a first incubation of the enzyme in the presence of MBI followed by
      a washing protocol to eliminate free MBI. Finally enzyme activity (initial
      velocity) is measured with specific substrate. The representation of the final
      equation obtained is a straight line, and the MBI-specific association constant
      of velocity (k) can be calculated from its slope. The mathematical model was then
      challenged with the effect of 18-ethynyl-11-deoxycorticosterone (18-EtDOC) as an
      MBI on aldosterone biosynthesis from 11-deoxycorticosterone (DOC) in rat adrenal
      mitochondria. The last step of the mitochondrial biosynthesis of aldosterone
      consists of the conversion of DOC into corticosterone (B) or 18-hydroxy-11
      deoxycorticosterone (18-OHDOC), and both steroids can then be transformed into
      aldosterone. The k (mM(-1) x min(-1)) values obtained for 18-EtDOC were: 451 +/-
      36 for DOC to aldosterone; 177 +/- 16 for B to aldosterone; 175 +/- 15 for 18
      OHDOC to aldosterone; and 2.7 +/- 0.2 for DOC to B. These results show that this
      MBI practically does not affect the metabolism of DOC to B in our enzyme
      preparation and that conversions of B and 18-OHDOC into aldosterone are catalyzed
      by the same enzyme.

PMID- 11226878
TI  - Gene structure and chromosomal location of a human bHLH transcriptional factor
      DEC1 x Stra13 x SHARP-2/BHLHB2.
AB  - DEC1/BHLHB2 is a novel cAMP-inducible basic helix-loop-helix (bHLH)
      transcriptional factor isolated from human chondrocyte cultures by the
      subtraction method [Shen et al. (1997) Biochem. Biophys. Res. Commun. 236, 294-
      298]. DEC1 seems to be involved in controlling the proliferation/differentiation
      of some cell lineages. We determined the structure of the human DEC1 gene and its
      chromosomal locus. Phylogenetic analysis and comparison of the gene structure
      showed that the DEC1 protein is a member of a new subgroup of the proline bHLH
      protein family that diverged earlier than other proline bHLH proteins including
      HES, hairy and E(spl). The human DEC1 gene spans approximately 5.7 kb and
      contains 5 exons. The putative promoter region contains multiple GC boxes but no
      TATA box. A primer extension study showed multiple transcriptional initiation
      sites. In the 5'-flanking region of the DEC1 gene, several transcriptional factor
      binding sites, including a cAMP-responsive element (CRE), were found using the
      transcription factor database. The DEC1 gene locates at Chromosome 3p25.3--26 by
      the FISH method. This is the first study to determine the genomic structure of
      the DEC1 gene subgroup.

PMID- 11226879
TI  - Monoacylglycerol lipase from moderately thermophilic Bacillus sp. strain H-257:
      molecular cloning, sequencing, and expression in Escherichia coli of the gene.
AB  - Monoacylglycerol lipase [MGLP, EC 3.1.1.23] is produced intracellularly by the
      moderately thermophilic Bacillus sp. strain H-257. The gene encoding MGLP was
      cloned, sequenced, and expressed in Escherichia coli. A genomic library of
      Bacillus sp. strain H-257, prepared in the plasmid vector pACYC184, was screened
      with a 0.2-kbp DNA fragment amplified by the polymerase chain reaction (PCR) with
      oligonucleotide primers designed based on the amino acid sequence of a purified
      MGLP. The plasmid pMGLP31, identified by hybridization with the amplified DNA
      fragment, contained a 5.3-kbp insert from Bacillus sp. strain H-257 DNA. Sequence
      analysis of the MGLP gene revealed an open reading frame encoding MGLP consisting
      of 250 amino acids, with a calculated molecular mass of 27.4 kDa. The deduced
      amino acid sequence of MGLP contained the consensus pentapeptide (-Gly-Xaa-Ser
      Xaa-Gly-), which is conserved among lipases, esterases, and serine proteases. The
      MGLP is homologous to a putative esterase/lipase from Streptomyces coelicolor
      (41.8% homology). When pMGLP31 was introduced into E. coli DH1, the transformants
      produced MGLP intracellularly as an active form to an approximately 13.8-fold
      greater extent than Bacillus sp. strain H-257. The purified recombinant MGLP was
      shown to be identical to the native enzyme in terms of chromatographic behavior,
      isoelectric point, and physicochemical and catalytic properties.

PMID- 11226880
TI  - Biochemical characterization of galloyl pedunculagin (ellagitannin) as a
      selective inhibitor of the beta-regulatory subunit of A-kinase in vitro.
AB  - The inhibitory effects of galloyl pedunculagin (GP) and eugeniin on the
      phosphorylation of histone H2B by cAMP-dependent protein kinase (A-kinase) and
      autophosphorylation of its beta-regulatory subunit (A-kinase beta) were examined
      in vitro. It was found that (i) GP (ID(50) = approx. 50 nM) effectively inhibits
      the activity of A-kinase (heterodimer), but high doses are required to inhibit
      the activities of the alpha-catalytic subunit (ID(50) = approx. 0.25 microM) and
      casein kinase II (CK-II, ID(50) = approx. 0.6 microM); (ii) GP inhibits the
      autophosphorylation of A-kinase beta in a dose-dependent manner with an ID(50) of
      approx. 6.6 nM, which is about 30-fold lower than that observed with CK-II beta;
      and (iii) GP reduces the suppressive effect of the beta-subunit on the activity
      of the alpha-subunit. In addition, purified bovine heart A-kinase precipitates
      when incubated with excess GP at pH 5.0. A similar precipitation of A-kinase was
      observed with eugeniin. These results show that the direct binding of GP to the
      beta-subunit prevents the physiological interaction between the beta- and alpha
      subunits of A-kinase in vitro. This conclusion is presumably consistent with the
      binding affinity of proline-rich proteins with tannins, since A-kinase beta
      contains a proline-rich domain that interacts with GP or eugeniin. Therefore, GP
      will serve as a powerful inhibitor for in vitro and in vivo cellular studies of A
      kinase beta-mediated signal transduction.

PMID- 11226881
TI  - Purification and characterization of homo- and hetero-dimeric acetate kinases
      from the sulfate-reducing bacterium Desulfovibrio vulgaris.
AB  - Two distinct forms of acetate kinase were purified to homogeneity from a sulfate
      reducing bacterium Desulfovibrio vulgaris Miyazaki F. The enzymes were separated
      from the soluble fraction of the cells on anion exchange columns. One acetate
      kinase (AK-I) was a homodimer (alpha(S)(2)) and the other (AK-II) was a
      heterodimer (alpha(S)alpha(L)). On SDS-PAGE, alpha(L) and alpha(S) subunits
      migrated as bands of 49.3 and 47.8 kDa, respectively, but they had an identical N
      terminal amino acid sequence. A rapid HPLC method was developed to directly
      measure ADP and ATP in assay mixtures. Initial velocity data for AK-I and AK-II
      were collected by this method and analyzed based on a random sequential
      mechanism, assuming rapid equilibrium for the substrate binding steps. All
      kinetic parameters for both the forward acetyl phosphate formation and the
      reverse ATP formation catalyzed by AK-I and AK-II were successfully determined.
      The two enzymes showed similar kinetic properties in Mg(2+) requirement, pH
      dependence and magnitude of kinetic parameters. These results suggest that two
      forms of acetate kinase are produced to finely regulate the enzyme function by
      post-translational modifications of a primary gene product in Desulfovibrio
      vulgaris.

PMID- 11226882
TI  - Studies on the hydrolyzing mechanism for cyclodextrins of Thermoactinomyces
      vulgaris R-47 alpha-amylase 2 (TVAII). X-ray structure of the mutant E354A
      complexed with beta-cyclodextrin, and kinetic analyses on cyclodextrins.
AB  - Crystals of the mutant E354A of Thermoactinomyces vulgaris R-47 alpha-amylase 2
      (TVAII) complexed with beta-cyclodextrin were prepared by a soaking method, and
      the diffraction data were collected at 100 K, using Synchrotron radiation (SPring
      8). The crystals belong to an orthorhombic system with the space group
      P2(1)2(1)2(1) and cell dimensions a = 111.1 A, b = 117.7 A, c = 113.3 A, which is
      almost isomorphous with crystals of the wild-type TVAII, and the structure was
      refined to an R-factor = 0.208 (R(free) = 0.252) using 3.0 A resolution data. The
      refined structure shows that the interactions between Phe286 and two C6 atoms of
      beta-cyclodextrin at the hydrolyzing site are important for TVAII to recognize
      cyclodextrins as substrates. This observation from the X-ray structure was
      supported by kinetic analyses of cyclodextrins using the wild-type TVAII, the
      mutant F286A and F286L. These studies also suggested that the TVAII-hydrolyzing
      mechanism for cyclodextrins is slightly different from that for starch.

PMID- 11226883
TI  - Interactions of human matrix metalloproteinase 7 (matrilysin) with the inhibitors
      thiorphan and R-94138.
AB  - The effects of the metalloproteinase inhibitors thiorphan and R-94138 on the
      matrilysin-catalyzed hydrolysis of (7-methoxycoumarin-4-yl)acetyl-L-Pro-L-Leu-Gly
      L-Leu-[N(3)-(2,4-dinitrophenyl)-L-2,3-diamino-propionyl]-L-Ala-L-Arg-NH(2) [MOCAc
      PLGL(Dpa)AR] were examined. The inhibitor constants (K(i)) of thiorphan and R
      94138 for matrilysin at pH 7.5, 25 degrees C were determined to be 11.2 and 7.65
      microM, respectively. From the temperature dependence of the K(i) values at pH
      7.5, the standard enthalpy change (Delta H degrees ') values for the binding of
      matrilysin with thiorphan and R-94138 were determined to be -(18.2 +/- 0.9) and
      (1.65 +/- 1.07) kJ x mol(-1), respectively. The binding of matrilysin to
      thiorphan is exothermic and the free energy change in the complex formation
      depends mainly on the change in enthalpy, while the binding to R-94138 is
      endothermic and typically entropy-driven. Hydrophobic interactions are suggested
      to contribute significantly to the binding of matrilysin to R-94138 as well as to
      the substrate. The pH dependence of the K(i) value suggests that at least two
      ionizing groups with pK(a) values of 4.5 and 9.1--9.3 are involved in the
      binding. The matrilysin activity is regulated by ionizing groups with pK(a)
      values of 4.3 and 9.6. Both inhibition and hydrolysis are suggested to be
      controlled by the same residues in matrilysin, most likely Glu 198 and Tyr 219,
      respectively.

PMID- 11226884
TI  - Functional role of the C-terminal domain of smooth muscle myosin light chain
      kinase on the phosphorylation of smooth muscle myosin.
AB  - Smooth muscle myosin light chain kinase (MLCK) is known to bind to thin filaments
      and myosin filaments. Telokin, an independently expressed protein with an
      identical amino acid sequence to that of the C-terminal domain of MLCK, has been
      shown to bind to unphosphorylated smooth muscle myosin. Thus, the functional
      significance of the C-terminal domain and the molecular morphology of MLCK were
      examined in detail. The C-terminal domain was removed from MLCK by alpha
      chymotryptic digestion, and the activity of the digested MLCK was measured using
      myosin or the isolated 20-kDa light chain (LC20) as a substrate. The results
      showed that the digestion increased K(m) for myosin 3-fold whereas it did not
      change the value for LC20. In addition, telokin inhibited the phosphorylation of
      myosin by MLCK by increasing K(m) but only slightly increased K(m) for LC20.
      Electron microscopy indicated that MLCK was an elongated molecule but was
      flexible so as to form folded conformations. MLCK was crosslinked to
      unphosphorylated heavy meromyosin with 1-ethyl-3-(3
      dimethylaminopropyl)carbodiimide in the absence of Ca(2+)/calmodulin (CaM), and
      electron microscopic observation of the products revealed that the MLCK molecule
      bound to the head-tail junction of heavy meromyosin. These results suggest that
      MLCK binds to the head-tail junction of unphosphorylated myosin through its C
      terminal domain, where LC20 can be promptly phosphorylated through its catalytic
      domain following the Ca(2+)/CaM-dependent activation.

PMID- 11226885
TI  - Apoptotic cells of an epithelial cell line, AsPC-1, release monocyte chemotactic
      S19 ribosomal protein dimer.
AB  - A pancreatic carcinoma cell line, AsPC-1, underwent apoptosis in vitro when heat
      treated for 60 min at 43 degrees C. Apoptotic AsPC-1 cells liberated a monocyte
      chemotactic factor into the culture supernatant 24 to 30 h after the heat
      treatment. This factor was immunologically identified as the cross-linked
      homodimer of S19 ribosomal protein (RP S19), since the majority of the
      chemotactic activity was absorbed by both anti--RP S19 rabbit antibodies and an
      anti--isopeptide bond monoclonal antibody immobilized on agarose beads.
      Intracellular transglutaminase activity increased during the apoptotic process,
      reaching the peak strength between 18 and 24 h after the heat-treatment. A
      recombinant RP S19 acquired the monocyte chemotactic capacity when incubated with
      the apoptotic cell extract obtained at the 18th hour. The chemotactic activity
      acquirement as well as the transglutaminase activity were blocked by treatment of
      the extract with anti--type II transglutaminase rabbit antibodies. When the
      recombinant RP S19 was treated with an authentic type II transglutaminase, the
      dimerization of RP S19 concomitant with the generation of the monocyte
      chemotactic activity was observed. Peptide-map analyses involving amino acid
      sequencing demonstrated that the inter-molecular isopeptide bond was
      heterogeneous: Gln12 or Gln137 and Lys29 or Lys122 were cross-linked. Site
      directed mutagenic analysis indicated that the cross-linking of Gln137, but not
      other residues such as Gln12, Lys29, and Lys122, was essential for expression of
      the chemotactic activity.

PMID- 11226886
TI  - Binding diversity of a noncovalent-type low-molecular-weight serine protease
      inhibitor and function of a catalytic water molecule: X-ray crystal structure of
      PKSI-527--inhibited trypsin.
AB  - PKSI-527 is a noncovalent-type low-molecular-weight inhibitor. The X-ray crystal
      structure of the trypsin-PKSI-527 complex revealed a binding mode (Form II)
      different from the previously reported one (Form I) [Nakamura, M. et al. (1995)
      Biochem. Biophys. Res. Commun. 213, 583--587]. In contrast to the previous case,
      the electron density of the inhibitor revealed the whole structure clearly. Each
      structural part of the inhibitor in Forms I and II was differently located at the
      active site, although the modes of binding of the terminal amino group to the
      Asp189 carboxyl group were similar. This binding diversity, which is a
      characteristic of the noncovalent-type low-molecular-weight inhibitor, provides a
      suitable example for estimating the possible mechanism toward the enzymatic
      inhibition, together with the structural basis necessary for a specific
      inhibitor. The mode of binding in Form II reflects the inhibitor-specific
      situation and is in contrast with the substrate-mimetic binding mode for Form I.
      Based on the generally accepted catalytic mechanism for serine protease, we
      propose that a water molecule located at the catalytic site plays an important
      role in blocking the catalytic function of the reactive Ser193 OH group.

PMID- 11226887
TI  - Crystal structure of Bacillus stearothermophilus alpha-amylase: possible factors
      determining the thermostability.
AB  - The crystal structure of a thermostable alpha-amylase from Bacillus
      stearothermophilus (BSTA) has been determined at 2.0 A resolution. The main-chain
      fold is almost identical to that of the known crystal structure of Bacillus
      licheniformis alpha-amylase (BLA). BLA is known to be more stable than BSTA. A
      structural comparison between the crystal structures of BSTA and BLA showed
      significant differences that may account for the difference in their
      thermostabilities, as follows. (i) The two-residue insertion in BSTA, Ile181
      Gly182, pushes away the spatially contacting region including Asp207, which
      corresponds to Ca(2+)-coordinating Asp204 in BLA. As a result, Asp207 cannot
      coordinate the Ca(2+). (ii) BSTA contains nine fewer hydrogen bonds than BLA,
      which costs about 12 kcal/mol. This tendency is prominent in the (beta/alpha)(8)
      barrel, where 10 fewer hydrogen bonds were observed in BSTA. BLA forms a denser
      hydrogen bond network in the inter-helical region, which may stabilize alpha
      helices in the barrel. (iii) A few small voids observed in the alpha-helical
      region of the (beta/alpha)(8)-barrel in BSTA decrease inter-helical compactness
      and hydrophobic interactions. (iv) The solvent-accessible surface area of charged
      residues in BLA is about two times larger than that in BSTA.

PMID- 11226888
TI  - Effect of ions and nucleotides on the interactions of yeast Rad51 protein with
      single-stranded oligonucleotides.
AB  - Rad51 protein is a eukaryotic homologue of RecA protein that is essential for
      homologous recombination. We developed a simple procedure for purifying yeast
      Rad51 protein, characterized its interaction with DNA, and compared it with those
      of RecA from Escherichia coli and Rad51 from higher eukaryotes. Fractionation of
      crude extract with 0.2% polyethylenimine eliminated contaminant proteins and
      nucleic acids, which can perturb the subsequent purification steps. Binding of
      Rad51 to single-stranded DNA was detected in solution by measuring the
      fluorescence anisotropy of a fluorescein probe attached to the 5' end of the
      oligonucleotides. The interaction was stabilized by ATP, as is that of RecA, but
      was neither stabilized by a non-hydrolysable analog of ATP, nor destabilized by
      ADP, unlike the interaction of RecA. This character was very similar to that of
      Xenopus XRad51.1, although the binding of yeast Rad51 to DNA was more sensitive
      to Mg(2+) ion in both the presence and absence of ATP, and was optimal at 5--10
      mM Mg(2+). The dissociation of Rad51 protein from DNA is not, therefore, favored
      by the hydrolysis of ATP to ADP, in contrast to that of RecA. On the other hand,
      the high DNA-binding state of the Rad51-DNA complex promoted by ATP appeared to
      be short-lived. These features may be linked to the lower activity of Rad51 and
      the fact that Rad51 activity does not require the hydrolysis of ATP.

PMID- 11226889
TI  - Cold adaptation of the thermophilic enzyme 3-isopropylmalate dehydrogenase.
AB  - We have performed random mutagenesis coupled with selection to isolate mutant
      enzymes with high catalytic activities at low temperature from thermophilic 3
      isopropylmalate dehydrogenase (IPMDH) originally isolated from Thermus
      thermophilus. Five cold-adapted mutant IPMDHs with single-amino-acid
      substitutions were obtained and analyzed. Kinetic analysis revealed that there
      are two types of cold-adapted mutant IPMDH: k(cat)-improved (improved in k(cat))
      and K(m)-improved (improved in k(cat)/K(m)) types. To determine the mechanisms of
      cold adaptation of these mutants, thermodynamic parameters were estimated and
      compared with those of the Escherichia coli wild-type IPMDH. The Delta G(m)
      values for Michaelis intermediate formation of the k(cat)-improved-type enzymes
      were larger than that of the T. thermophilus wild-type IPMDH and similar to that
      of the E. coli wild-type IPMDH. The Delta G(m) values of K(m)-improved-type
      enzymes were smaller than that of the T. thermophilus wild-type IPMDH. Fitting of
      NAD(+) binding was improved in the K(m)-improved-type enzymes. The two types of
      cold-adapted mutants employed one of the two strategies of E. coli wild-type
      IPMDH: relative destabilization of the Michaelis complex in k(cat)-improved-type,
      and destabilization of the rate-limiting step in K(m)-improved type mutants. Some
      cold-adapted mutant IPMDHs retained thermostability similar to that of the T.
      thermophilus wild-type IPMDH.

PMID- 11226891
TI  - [The philosophical cafe].

PMID- 11226890
TI  - Cloning of cDNA for cathepsin B mRNA 3'-untranslated-region-binding protein
      (CBBP), and characterization of recombinant CBBP.
AB  - Previously, we purified the cathepsin B mRNA 3'-untranslated-region-binding
      protein (CBBP) from Sarcophaga and suggested its participation in the
      translational regulation of cathepsin B mRNA in this insect. In this study, we
      isolated a full length cDNA for CBBP. CBBP was an RNA-binding protein that
      contained four RGG boxes and four zinc finger motifs required for RNA binding.
      CBBP was shown to be localized in both the nuclei and cytoplasm of Sarcophaga
      hemocytes. Recombinant CBBP bound to the entire region of cathepsin B mRNA and
      repressed its translation in vitro.

PMID- 11226892
TI  - [Antiphospholipid syndrome].

PMID- 11226894
TI  - [Epidemiology study of Hansen's disease in metropolitan France between 1995 and
      1998].
AB  - BACKGROUND: The last epidemiology study on leprosy in metropolitan France was
      done in 1970 - 1978. We performed a new evaluation of the situation close to
      2000, the date the World Health Organization has targeted for the "eradication of
      leprosy". PATIENTS AND METHODS: This retrospective study was conducted on data
      from 1995-1998 obtained from inquiries to 105 dermatology (56), infectious
      disease (41) and neurology (8) units. RESULTS: Response rate was 86 p. 100. In
      1998, 232 patients were under surveillance, mainly in dermatology units (81 p.
      100). Sixty-nine patients were taking an antibacillar treatment, giving a very
      low prevalence of 0.013 per 10 000 inhabitants. On the average, 18 new cases were
      observed per year over the four years studied (range 16-20). Thirty-seven percent
      of these new cases were French, from metropolitan areas (38 p. 100) or from
      overseas (62 p. 100). DISCUSSION: Our study confirms the persistence of new cases
      of leprosy identified in metropolitan France over these last years. The number is
      quite similar to that noted in the earlier survey, excepting the years 1975-1997
      when there was an influx of immigrants from Southeast Asia that led to a rise in
      the number of new cases. Approximately one-third of the cases in the present
      survey were in French from metropolitan areas or overseas departments. None of
      these cases observed originated in metropolitan France since a trip to an endemic
      area was found in all new cases and no new case was observed in the families of
      newly identified patients.

PMID- 11226893
TI  - [Basal cell carcinoma of the vulva: 21 cases].
AB  - INTRODUCTION: Basal cell carcinoma (BCC) accounts for 2 to 3 p. 100 of all vulvar
      malignancies. PATIENTS AND METHODS: We report a retrospective study of 21 cases
      treated from 1937 to 1999. RESULTS: Vulvar BCC's occurred in elderly patients
      (average age: 66 years), with mean delay to diagnosis of 5.5 years. Five patients
      were referred for recurrence. Lesions were located on the external hairy side of
      the labia majus, except one located on the internal side. In 4 cases a
      preexisting risk factor was identified: 2 patients had previously received
      radiation therapy and 2 other patients had multiple disseminated BCC. Mean BCC
      diameter was 2 cm. Pathological data were similar to skin BCC, with one case of
      mixed tumor (BCC and squamous cell carcinoma). The treatment was surgical
      excision for 19 BCCs. Local recurrence risk was high. Only one patient died of
      visceral dissemination of the disease. DISCUSSION: More than 250 cases of vulvar
      BCC have been reported in the literature. Clinical, pathological and follow up
      data are similar to results in the present series. Treatment of choice consists
      of surgical excision with tumor-free margins. Because of local recurrence risk
      and possible association with other primary cancers in this age group, long term
      follow-up is necessary.

PMID- 11226895
TI  - [Psychological approach to different skin diseases: life events and tendency to
      complain].
AB  - BACKGROUND: For nearly two decades, dermatology has associated with psychology to
      find a better way to care for dermatology conditions. A scientific trend called
      psychosomatics is creating a link between dermatology and psychology. OBJECTIVE:
      The purpose of this article was to examine two concepts closely linked to
      psychodermatology (life events and tendency to complain) and to emphasize the
      difference between factors playing a role in the onset of certain skin diseases
      (psoriasis, alopecia areata, benign tumors, eczema). RESULTS: We found that
      psoriasis patients have a greater tendency to complain than people with the other
      disease. This point to the importance of taking emotions into account when
      studying psoriasis. We also found that life events play a role in the onset of
      psoriasis and alopecia areata. Moreover, these events were anterior by more than
      12 months in alopecia patients. CONCLUSION: We propose exploring emotions in
      psoriasis patients and life events over the prior year in alopecia areata
      patients.

PMID- 11226896
TI  - [Cutaneous delayed hypersensitivity reactions to heparins and heparinoids].
AB  - INTRODUCTION: Due to cross-reactions between unfractionated heparins, low
      molecular-weight heparins and sometimes heparinoids, cutaneous delayed
      hypersensitivity reactions might be a problem for the choice of therapeutic
      alternative. We report on two cases of sensitization to heparins and heparinoids.
      OBSERVATIONS: One woman developed localized skin reaction to a low-molecular
      weight heparin, then a generalized maculopapular rash when an intravenous
      injection of unfractionated heparins was performed. The second patient had a
      localized then extended reaction to a low-molecular-weight heparin and was
      referred for the choice of a well tolerated method to obtain anticoagulation
      during a pulmonary surgery. METHODS: Patch tests, prick tests, intradermal and
      subcutaneous tests were performed with several unfractionated heparins, low
      molecular-weight heparins, danaparoid and lepirudin in both cases. RESULTS: In
      the first case, tests performed with both heparins and heparinoid were positive
      and the use of lepirudin was proposed if anticoagulation was necessary. In the
      second case the subcutaneous danaparoid injection induced a localized reaction on
      the injection site. Danaparoid injections were continued associated with
      localized applications of dermocorticoids without any side effect. DISCUSSION:
      Cutaneous delayed hypersensitivity reactions occur on the injection site but can
      also be generalised. Cross reactions might be unexpected therefore skin-tests are
      necessary to guide the choice of a therapeutic alternative. In case of
      intolerance to both heparins and heparinoids various solutions may be proposed
      such as the application of topical corticosteroids on the injection site or the
      administration of hirudins. There is no cross sensitization between heparins and
      hirudins, but the use of hirudins is restricted and requires specific monitoring.

PMID- 11226897
TI  - [Paraneoplastic acquired ichthyosis revealing non-Hodgkin's lymphoma].
AB  - BACKGROUND: Paraneoplastic ichthyosis is a rare affection generally associated
      with malignant hemopathy. CASE REPORT: A 61 year-old man was seen with a
      generalized ichthyosis associated with a palmoplantar hyperkeratosis developed
      over the last 2 years, and an axillary lymph node. Histology of the lymph node
      revealed a large cell anaplastic lymphoma. Both ichthyosis and palmoplantar
      keratosis totally disappeared three weeks after adenectomy, without any other
      treatment. DISCUSSION: This rapid and complete regression of ichthyosis, after
      the sole ablation of the involved lymph node confirmed the paraneoplastic nature
      of the disorders of the keratinization (ichtyosis, palmoplantar keratodermia).
      The review of the literature showed only one case characterized by a rapid
      disappearance of ichthyosis after surgical treatment of the malignant lymphoma.

PMID- 11226898
TI  - [Plaque variant of trichoblastic fibroma].
AB  - BACKGROUND: Tricoblastic fibroma is a rare benign skin tumor originating in the
      hair follicle. There are two clinical presentations: nodular and plaque variants.
      The plaque variant is almost exclusively located on the face with deep tissue
      infiltration. CASE REPORT: A 38-year-old man presented with a 2 cm diameter
      cutaneous plaque located on the right cheek. It had first been noted by the
      patient 3 years earlier and had enlarged slowly. On examination, the plaque was
      well defined, yellowish and slightly indurated. The first clinical diagnosis was
      basal cell carcinoma and the plaque was removed. Histology provided the diagnosis
      of trichoblastic fibroma. The patient remains well, with no evidence of
      recurrence, 10 months after excision. DISCUSSION: Trichoblastoma is an inclusive
      term for all benign cutaneous neoplasms that are mostly composed of follicular
      germinative cells. According to Altman, the plaque variant of trichoblastic
      fibroma is a poorly circumscribed neoplasm, particularly at its lateral and deep
      margins. This author also states that mitotic figures are more numerous in the
      plaque variant of trichoblastic fibroma and considers this clinical variant as a
      low-grade follicular malignancy.

PMID- 11226899
TI  - [Cutaneo-systemic papulosclerotic mucinosis (scleromyxedema): remission after
      extracorporeal photochemotherapy and corticoid bolus].
AB  - INTRODUCTION: Scleromyxedema is the consequence of a dermal infiltration by
      mucine, commonly associated with a monoclonal gammapathy of unknown significance.
      CASE REPORT: A 46 year-old woman was hospitalized for a scleromyxedema with a
      bilateral macular edema and a restricted pulmonary syndrome. A quite complete
      cutaneous response and a complete ocular and pulmonary response were obtained
      after 12 extracorporeal photopheresis courses and 4 flashes of prednisolone (17
      months follow-up). COMMENTS: There is no consensus on guidelines for the
      treatment of scleromyxedema. Steroids and melphalan are usually indicated.
      However these drugs induce severe side-effects. In the absence of controlled
      studies concerning the efficiency of the different drugs used in scleromyxedema,
      the main advantage of photopheresis lies in the safety of this procedure.

PMID- 11226900
TI  - [Severe chronic actinic dermatitis treated with cyclosporine: 2 cases].
AB  - INTRODUCTION: The treatment of the severe forms of photodermatoses often requires
      potent systemic immunosuppressive drugs. We report two patients suffering from
      severe photodermatitis successfully treated with oral cyclosporine. CASES REPORT:
      A 58-year-old man developed severe pruritic eczematous reactions for several
      years on light-exposed and light-protected skin following each sun exposure. A 66
      year-old man showed similar lesions restricted to the head and neck. The clinical
      presentation and evolution as well as histologic, immunohistologic, allergologic
      and photobiologic assessments suggested the diagnosis of actinic reticuloid and
      persistent light reactivity, respectively. The lesions of both patients did not
      respond to a high dose regimen of systemic corticosteroids (methylprednisolone 1
      mg/kg/day) for several weeks. The severity of cutaneous lesions and pruritus
      required another potent immunosuppressive treatment. Oral cyclosporine at the
      maximum daily dose of 4 mg/kg was given for three months. A rapid improvement of
      the pruritus and skin lesions occurred in the two patients, without significant
      side-effect. The first patient experienced recurrent lesions after termination of
      cyclosporine treatment during summer time. The other patient did not develop new
      skin eruption for 3 years after stopping the initial treatment with cyclosporine.
      DISCUSSION: Low-dose oral cyclosporine is a quick-acting and well tolerated
      symptomatic treatment of severe photodermatoses resistant to other systemic
      immunosuppressive drugs. However, therapeutic results do not consistently exhibit
      long-standing remanent effect.

PMID- 11226901
TI  - [Photoallergic reactions to olaquindox in swine raisers: role of growth promotors
      used in feed].
AB  - BACKGROUND: The diagnosis of photodermatosis is generally facilitated by the
      typical localization of the eruption. The causal agent can usually be identified
      by history taking, allowing eviction and cure. It may be difficult to find the
      causal agent in cases with a sequential course. The occupational and/or
      recreational environment may provide helpful information. We present two cases of
      photodermatosis related to the occupational environment. CASE REPORTS: A 50-year
      old woman and a 29-year-old man were farm workers. both consulted for
      photoinduced eczema. The eczema was triggered by episodic manipulation of an
      antibiotic used widely for preparing animal feed. The standard allergy tests were
      negative. The photobiology exploration led to the diagnosis of photoallergy to
      olaquindox, a growth promotor added to animal feed. The course was favorable
      after eviction or protection against the product, providing a complementary proof
      of its triggering effect. DISCUSSION: We emphasize the contribution of
      photobiological explorations in difficult cases with an occupational background.
      Generally, these patients are unaware of the composition of the products
      manipulated, such as feed additives.

PMID- 11226903
TI  - [Loose anagen hair syndrome: a familial case with fetal hair in meconium].
AB  - INTRODUCTION: Loose anagen hair syndrome is a recently described hair disorder.
      We report a familial case. CASE REPORT: Two sisters were examined, 4 years-old
      and 8 months old, from a consanguineous marriage. At birth, they presented
      diffuse alopecia of the scalp; the meconium contained black and silky hair.
      Clinical examination noted the short, fine hair with easy and painless uprooting.
      No clinical associated symptoms were observed. The trichogram showed 70 p. 100 of
      anagen hair and 30 p. 100 of telogen hairs. DISCUSSION: Our familial case is
      original by this clinical symptom: discharge of probably dystrophic foetal hair
      in the meconium. Loose anagen hair is characterised by easily pluckable hair. The
      trichogram confirms the diagnostic. It is composed of anagen hairs (80 to 100 p.
      100) devoid of sheaths. The loose anagen hair is usually isolated, but
      associations have been reported. It may occur in families. The precise
      pathogenesis and treatment of this hair disorder are not known.

PMID- 11226902
TI  - [Cutaneous lupus erythematosus following argon laser treatment].
AB  - BACKGROUND: It is well known that exposure to ultraviolet light can trigger lupus
      manifestations. Other light sources may have the same effect. We report a case of
      argon laser-induced lupus erythematosus. CASE REPORT: A 59-year-old women
      developed an erythematous edematous infiltrated and sensitive lesion over the
      right cheek ten days after an argon laser treatment of the retina. The lesion
      spread towards the chin despite antibiotic treatment. Histology examination of a
      biopsy specimen and direct immunofluorescence suggested the diagnosis of
      cutaneous lupus erythematosus. The lesions regressed in one month with
      hydroxychloroquine (400 mg/d) treatment. DISCUSSION: Our patient developed argon
      laser induced cutaneous lupus erythematosus. It is known that ultraviolet light
      and non-ultraviolet frequencies (x-rays, visible light) can induce lupus
      manifestations. One case of discoid lupus erythematosus after argon laser has
      been reported. In our case, due to a technical error the laser beam was directed
      onto the ipsilateral cheek during the laser treatment of the retina. The low
      energy beams used in ophthalmology would explain the absence of local burn but
      would be sufficient to trigger lupus. This case demonstrates that argon laser, a
      visible blue or green beam, can provoke cutaneous lupus erythematosus even if
      there is no heat-induced burn. It is important to be aware of this adverse effect
      due to the widespread use of lasers in dermatology, particularly for the
      treatment of cutaneous lupus lesions.

PMID- 11226904
TI  - [Eruptive pseudoangiomatosis in an adult renal transplant recipient].
AB  - BACKGROUND: In 1969, Cherry et al. described four children with acute onset
      angioma-like papules with spontaneous regression during an acute viral infection.
      Similar cases, called eruptive pseudoangiomatosis, have been reported since and
      considered to be a viral exanthema. We observed a similar eruption in a 48-year
      old male kidney transplant recipient. CASE REPORT: One month after kidney
      transplantation, the patient rapidly developed macules and papules on the trunk.
      He had unexplained fever 15 days before the eruption. A biopsy specimen revealed
      dermal blood vessels surrounded by lymphoid infiltrate. Serology tests were
      unable to identify any virus. The lesions resolved spontaneously within 15 days.
      DISCUSSION: In our patient, eruptive pseudoangiomatosis was diagnosed on the
      basis of the clinical and histological features and the disease course. This case
      demonstrates that the entity is not limited to children. Further cases should be
      studied to determine the precise pathogenics of this uncommon entity.

PMID- 11226905
TI  - [Facial nerve. Particular aspects of the cervicofacial anatomy].

PMID- 11226906
TI  - [Pigmentary maculae of the large folds].

PMID- 11226907
TI  - [Lymphocyte infiltration in superficial dermis].

PMID- 11226908
TI  - [Searching for sarcoptes].

PMID- 11226909
TI  - [Hypersensitivity to balsam of Peru (Myroxylon pereirae)].

PMID- 11226910
TI  - [Acute generalized exanthematic pustulosis].

PMID- 11226911
TI  - [Nodular hypodermitis].

PMID- 11226912
TI  - [Melkersson-Rosenthal syndrome].

PMID- 11226913
TI  - [Air pollution and health].

PMID- 11226914
TI  - [Surveillance of short-term effects of urban air pollution on mortality. Results
      of a feasibility study in 9 French cities].
AB  - BACKGROUND: This study aims at quantifying air pollution effects on mortality and
      at evaluating the feasibility of a standardized epidemiological surveillance
      system of air pollution in 9 French cities. METHODS: Data collection and analysis
      followed a standardized protocol. Data pollution depended on the development of
      local air quality surveillance networks (number of indicators, number of
      stations.). The Generalised Additive Models (GAM) were used to quantify the
      association between air pollution and mortality. RESULTS: In the 9 studied areas,
      associations between all causes, cardiovascular and respiratory mortality, and
      air pollution indicators were observed. These associations were linear without
      threshold. Depending on the pollutants, excess in mortality related to an
      interquartile increase in acid-particulate pollution varied between 0.3 and 3.5%
      for total mortality, 0.5 and 6.3% for cardiovascular mortality, and between 0.1
      and 12% for respiratory mortality. Photochemical air pollution varied between 0.4
      and 7.3% for total mortality, 1.4 and 6.7% for cardiovascular mortality, and
      between 1.7 and 30.4% for respiratory mortality. CONCLUSION: In spite of a
      standardized common protocol, some disparities, inherent to the local
      characteristics, were noted (length of time series, numbers of ambient urban
      stations selected and pollutants available.). Nevertheless, this pilot study
      showed that multicentric epidemiological monitoring of air pollution effects on
      health was feasible. Yet, this requires to validate the results obtained through
      a re-analysis of the mortality data on a longer period of study. It also requires
      to study the feasibility and the relevance of the use of other health indicators,
      such as hospital admissions.

PMID- 11226915
TI  - [Air pollution and myocardial infarction. Strasbourg France, 1984-89].
AB  - BACKGROUND: Many studies have shown positive associations between urban air
      pollution, mortality and hospitalizations for cardiovascular diseases. This study
      tried to estimate short term effects of ambient air pollution on myocardial
      infarction on the basis of data collected in a morbidity registry. METHODS: The
      daily number of myocardial infarctions between 1984 and 1989 was supplied by the
      Monica registry (Bas-Rhin). The pollution variables were daily mean and maximum
      of hourly measures of carbon monoxyde (CO), sulfur dioxide (SO(2)), particles
      (PM13), nitrogen monoxyde (NO) and nitrogen dioxide (NO(2)), mean and maximum of
      hourly measures of ozone (O(3)) between 10 a.m. and 6 p.m. Other data were
      influenza epidemics, daily temperature and humidity. The analysis was a Poisson
      regression controlling for trend, season, meteorological factors and pollutant,
      using non parametric smoothing. Influence of day of week and influenza were
      controlled through dummy variables. RESULTS: For the hourly maximum of NO with a
      5 day lag the association was statistically significant (square root relation):
      for an increase from percentile 25 (63 microg/m(3)) to percentile 75 (189
      microg/m(3)), the RR was 1.087 (95% CI: 1.014-1.166). The association was
      significant during winter with a RR of 1.129 (95% CI: 1.028-1.241) for a
      percentile 25 (101 microg/m(3)) to percentile 75 (265 microg/m(3)) increase. A
      positive linear association was found with daily maximum of NO(2) during winter
      with a 5 day lag: the RR, for an increase from percentile 25 (59 microg/m(3)) to
      percentile 75 (107 microg/m(3)) was 1.095 (95% CI: 1.015-1.181). For the daily
      mean and maximum of O(3), a positive association was found but it was not robust.
      For other pollutants, no association was found. CONCLUSIONS: The association
      between NO(2) and coronary events, hospitalizations and mortality, has been shown
      in several studies but not in all. This secondary pollutant could be a proxy for
      small particles.

PMID- 11226916
TI  - [Incidence of fractures after the age of 50 years in the Lebanese population and
      implications in terms of osteoporosis].
AB  - BACKGROUND: No comprehensive population-based data is available on the incidence
      of fractures in Lebanon and the Middle-East. The aim of this study was to
      estimate the incidence of osteoporotic fractures in the Lebanese population aged
      50 years and over. METHODS: In 1997, a cross-sectional population-based random
      sample of individuals aged 50 years and over was selected using a multiple level
      cluster sampling technique. Selected individuals responded to an Arabic version
      of the EULAR questionnaire. A fracture was defined as incident if it had occurred
      within the last year. The lifetime risk of osteoporotic fracture was estimated
      using the incidence rate by ten-year age groups assuming that each individual
      counts on the average for half the interval. RESULTS: 1003 individuals were
      included. There were 496 men (49.5%) and 507 women (50.5%). Mean age was 61.3
      years (CI: 60.8-61.8) with a maximum of 88 years. The observed number of
      fractures was 111, giving an absolute risk of osteoporotic fractures of 11.1%
      (CI: 9.1-12.9). It was higher in women, 13.0% (CI: 10.9-15.1) than in men, 8.6%
      (CI: 6.9-9.3). Female to male ratio was 1.6. The estimated annual incidence was
      2.6% (CI: 2.0-3.2), higher in women, 3.8% (CI: 2.2-5.5) than in men, 1.4% (CI:
      0.4-2.5). Incident cases were distributed as follows: 4-hip, 4-forearm, 3-spine,
      and 15 other sites. Annual incidence was higher in women than in men for all
      sites. Estimated lifetime risk of osteoporotic fracture was 9.3% (CI: 6.7-11.9)
      in men and 16.7% (CI: 13.4-19.9) in women. CONCLUSION: Our figures are lower than
      those found in Northern Europe but are higher than in Asian countries, possibly
      reflecting a west-east gradient in risk factors.

PMID- 11226917
TI  - Body mass index: comparing mean values and prevalence rates from telephone and
      examination surveys.
AB  - BACKGROUND: Cost effective means of assessing the levels of risk factors in the
      population have to be defined in order to monitor these factors over time and
      across populations. This study is aimed at analyzing the difference in population
      estimates of the mean levels of body mass index (BMI) and the prevalences of
      overweight, between health examination survey and telephone survey. METHODS: The
      study compares the results of two health surveys, one by telephone (N=820) and
      the other by physical examination (N=1318). The two surveys, based on independent
      random samples of the population, were carried out over the same period (1992
      1993) in the same population (canton of Vaud, Switzerland). RESULTS: Overall
      participation rates were 67% and 53% for the health interview survey (HIS) and
      the health examination survey (HES) respectively. In the HIS, the reporting rate
      was over 98% for weight and height values. Self-reported weight was on average
      lower than measured weight, by 2.2 kg in men and 3.5 kg in women, while self
      reported height was on average greater than measured height, by 1.2 cm in men and
      1.9 cm in women. As a result, in comparison to HES, HIS led to substantially
      lower mean levels of BMI, and to a reduction of the prevalence rates of obesity
      (BMI>30 kg/m(2)) by more than a half. These differences are larger for women than
      for men. CONCLUSION: The two surveys were based on different sampling procedures.
      However, this difference in design is unlikely to explain the systematic bias
      observed between self-reported and measured values for height and weight. This
      bias entails the overall validity of BMI assessment from telephone surveys.

PMID- 11226918
TI  - [Relevance and validity of a new French composite index to measure poverty on a
      geographical level].
AB  - BACKGROUND: A number of disease conditions are influenced by deprivation.
      Geographical measurement of deprivation can provide an independent contribution
      to individual measures by accounting for the social context. Such a geographical
      approach, based on deprivation indices, is classical in Great Britain but
      scarcely used in France. The objective of this work was to build and validate an
      index readily usable in French municipalities and cantons. METHODS: Socioeconomic
      data (unemployment, occupations, housing specifications, income, etc.) were
      derived from the 1990 census of municipalities and cantons in the Doubs
      departement. A new index was built by principal components analysis on the
      municipality data. The validity of the new index was checked and tested for
      correlations with British deprivation indices. RESULTS: Principal components
      analysis on municipality data identified four components (explaining 76% of the
      variance). Only the first component (CP1 explaining 42% of the variance) was
      retained. Content validity (wide choice of potential deprivation items,
      correlation between items and CP1: 0.52 to 0.96) and construct validity (CP1
      socially relevant; Cronbach's alpha=0.91; correlation between CP1 and three out
      of four British indices ranging from 0.73 to 0.88) were sufficient. Analysis on
      canton data supported that on municipality data. CONCLUSION: The validation of
      the new index being satisfactory, the user will have to make a choice. The new
      index, CP1, is closer to the local background and was derived from data from a
      French departement. It is therefore better adapted to more descriptive approaches
      such as health care planning. To examine the relationship between deprivation and
      health with a more etiological approach, the British indices (anteriority,
      international comparisons) would be more appropriate, but CP1, once validated in
      various health problem situations, should be most useful for French studies.

PMID- 11226919
TI  - [ A registry of ischaemic cardiopathies among active workers at Electricite de
      France-Gaz de France. Program development and first results].
AB  - BACKGROUND: The social security department of the French national electric and
      gas company has established an ischemic heart disease register among a population
      of about 140 000 employees based on sick leaves as well as deaths recorded with
      their medical cause. METHODS: History of the illness, medical tests and
      treatments were known retrospectively from the consulting physicians of the
      company. Acute coronary events recorded were: inaugural angina pectoris,
      myocardial infarction, sudden coronary death and fortuitous discovery of coronary
      disease. RESULTS: A first study conducted on employees during the 1993-1995
      period showed infarction incidence age rates similar to those estimated from the
      French MONICA registers for France as a whole. Regional discrepancies were
      observed for myocardial infarction rates: Nord-Pas de Calais, Champagne-Ardennes,
      Lorraine, Franche-Comte and Limousin were at the most elevated risk (SIR=131,
      155, 169, 125 and 178 resp). Large variations according to socio-economic status
      were observed. CONCLUSION: This register will permit studies on the links between
      socio-economic status at different professional career points and the occurrence
      of ischemic heart disease and the evaluation of the impact of psychosocial
      factors such as previous depressive disorders.

PMID- 11226920
TI  - [Short term effect of urban air pollution on respiratory insufficiency due to
      chronic obstructive pulmonary disease. Synthesis of studies published from 1962
      to January 2000].
AB  - This review presents a synthesis of studies published from 1962 to 2000 on the
      relations between air pollution and chronic obstructive pulmonary disease (COPD):
      12 ecological epidemiological studies, 6 epidemiological panel studies, and 11
      controlled human exposure trials. The controlled trials, ecological time-based
      epidemiological studies and panels are examined successively followed by a
      discussion of their methodology and results. The controlled trials either do no
      highlight effects or show effects having no clinical significance since
      variations are similar to physiological variability. For epidemiological studies
      reporting individual data, the results point to a particle effect (two studies).
      This effect of particles is found in ecological studies which also describe an
      impact of ozone, sometimes of sulfur dioxide and less often of nitrogen dioxide.
      In conclusion, patients suffering from COPD are generally regarded as a group
      sensitive to air pollution, as suggested by the results of numerous ecological
      epidemiological studies. Rare individual studies provide a few arguments
      supporting this assumption.

PMID- 11226921
TI  - [Assessment of exposure to atmospheric particles: contribution of individual
      measurements].
AB  - BACKGROUND: There are few studies of individual exposure to atmospheric
      particles, because of the relatively bulky and noisy sampling devices. These
      personalized measurements, generally associated with micro-environmental
      measurements, are aimed at studying the distribution of individual exposure and
      identifying its main determinants. METHODS: A synopsis of the methods implemented
      in such studies (populations studied, measurements strategies, questionnaires on
      time-activity patterns, residences and work place) was detailed. The major
      results are presented and discussed from an epidemiological point of view.
      RESULTS: The individual exposure measured with portable devices generally were
      generally found to be higher than the estimations made by combining micro
      environmental (outdoor and indoor) measurements and data from time-activity
      diaries. The difference between results of these two approaches, known as
      "personal cloud", remains poorly understood. Correlations between individual
      measurings and outdoor concentrations are weak; nevertheless, day to day
      variations of these two series of measurements are better related. The main
      determinants of individual exposure to particles are identified but a
      quantification of their contribution remains difficult, except for passive
      smoking. CONCLUSION: Personal measurements cannot be used to estimate particle
      exposure in large scale epidemiological studies. This exposure needs to be
      modelized.

PMID- 11226922
TI  - [Phone prompt or mailed reminder for increasing response rate among
      investigators? A randomized trial in the Sentinelles network].

PMID- 11226923
TI  - [The responsibility of the tobacco industry in the smoking pandemic].

PMID- 11226924
TI  - [Noninvasive ventilation: current concepts in the treatment of chronic
      respiratory failure in patients with chronic obstructive lung disease].
AB  - Long-term oxygen therapy remains the mainstay treatment for advanced-stage
      chronic obstructive pulmonary disease that has reached the state of chronic
      respiratory failure. Noninvasive ventilation should be discussed for some
      patients with a instability and frequent hospitalizations for decompensation and
      progressive degradation of blood gases. Although this subpopulation remains to be
      perfectly defined, it is reasonable to discuss the implementation of noninvasive
      ventilation at night in association with daytime oxygen therapy for patients who
      do not respond to well conducted and well-implemented oxygen therapy if the
      disease instability is marked by an increasing rate of hospitalizations for
      decompensation. This subpopulation includes COPD patients with a worsening PaCO2
      above 50 mmHg.

PMID- 11226925
TI  - [Regulations on tuberculosis risk in workplaces in Senegal].
AB  - National immunization and control programs have not brought about a significant
      decline in tuberculosis, which remains a real public health concern in our
      regions. Prevention in the working environment should be part of an overall
      prevention program for the general population. Nevertheless, companies should
      play a leading role because they have the necessary structure and assets. We
      analyzed the epidemiology of tuberculosis in the working environment using
      demographic data on employees in Senegal, current medicolegal data on
      tuberculosis in Senegal and data on prevention of tuberculosis. Our analysis led
      to a proposed strategy for controlling tuberculosis spread and its prevention in
      the working environment in Senegal.

PMID- 11226926
TI  - [Radiological evidence of lung involvement in metal fume fever].
AB  - We report the case of a 32-year-old welder who developed a flu-like syndrome a
      few hours after founding zinc. The patient experienced fever, headache, muscle
      pain and dyspnea that resolved spontaneously with a few hours. The diagnosis of
      metal fume fever was retained. The chest x-ray evidenced bilateral diffuse
      infiltrative pulmonary lesions, rarely described in this syndrome. Metal fume
      fever is a likely diagnosis in exposed patients who develop fever with diffuse
      lung involvement.

PMID- 11226927
TI  - [Pulmonary lymphangioleiomyomatosis in a menopaused woman].
AB  - We report an unusual case of pulmonary lymphangioleiomyomatosis in a menopaused
      woman who had been taking estrogen hormone replacement therapy for several years.
      The characteristic feature of this uncommon disease is a proliferation of non
      tumoral abnormal smooth muscle cells within the alveolar walls, and around the
      bronchi, lymph nodes and blood vessels. About twenty cases of pulmonary
      lymphangioleiomyomatosis have been described in menopaused women, who generally
      were taking estrogen hormone replacement therapy. This subpopulation does not
      appear to present any particular clinical, functional or radiographic features.

PMID- 11226928
TI  - [Spontaneous idiopathic chylothorax. Case report and review of the literature].
AB  - We present a new case of bilateral spontaneous idiopathic pneumothorax, occurring
      in a 52-year-old woman. A literature review of similar cases shows a quite
      reproducible picture, consisting in the occurrence of supraclavicular swelling
      and left or bilateral chylothorax after a mild effort in a woman in her fifties.

PMID- 11226929
TI  - [An uncommon cause of persistent fever in France].
AB  - Miliary tuberculosis is rare and requires rapid diagnosis. Outcome is fatal in
      25% of the cases. Since radiography and laboratory tests contribute little to
      early diagnosis, clinical findings are primordial. Antituberculosis antibiotic
      therapy is frequently started before microbiological confirmation of the
      diagnosis.

PMID- 11226930
TI  - [Anaphylactic reaction to a dog?].

PMID- 11226931
TI  - [Post-cardiac aggression syndrome: a case report].

PMID- 11226932
TI  - [Accumulation and biomagnification of organochlorine insecticides in molluscs and
      fish of the Moulay Bouselham lagoon, Morocco].
AB  - We studied the contamination by organochlorine insecticides of the clams and eels
      in Moulay Bousselham lagoon, on the west coast of Morocco. DDT and its
      metabolites, DDE and DDD, were found to have accumulated in the lipids of all
      specimens. Organochlorine concentration in clams was highest for samples taken
      from the mouth of channels draining agricultural land. Organochlorine content was
      more than 100 ng/g in some cases in this area, whereas it was less than 40 ng/g
      in the rest of the lagoon. Organochlorine content peaked in May and then
      decreased after egg laying. Marked concentration of these pesticides was observed
      in eels, which are mobile and carnivorous. Organochlorine content peaked in
      November, mainly among the large specimens preparing to migrate to the ocean. DDT
      was stored in lipids, at concentrations up to 2,000 ng/g. However, even this high
      concentration is below the upper limit for human consumption. The higher
      proportion of DDE than of DDT shows that most of the contamination is not recent.
      BHC and cyclodienes were also detected, at low concentrations. The contamination
      of eels and clams in the Moulay Bouselham does not currently pose a threat to
      public health.

PMID- 11226933
TI  - [Contamination of the Moulay Bouselham Lagoon, Morocco with organochlorine
      pesticides and nitrates].
AB  - In the lagoon system of Moulay Bouselham, on the Atlantic coast of Morocco,
      drainage bring nutriments and sediments from irrigation systems to the open
      lagoon. The recent intensification of farming in the surrounding area is the
      chief cause of this. We studied the chemical pollution of the lagoon, which
      serves as a nature reserve, by analyzing the nitrate content of the water and the
      organochlorine pesticide content of the sediment. Comparison with similar
      ecosystems showed that the sediments were only moderately contaminated. However,
      the level of nitrates in the water was found to exceed the upper limit of the
      range of concentrations considered safe for human health in European regulations.
      The level of nitrate pollution in the area seems to be increasing, whereas
      organochloride pesticide pollution is on the decrease. The washing out of
      fertilizer during winter is responsible for much of the nitrate pollution in this
      season whereas in summer, urban effluents is the chief cause of nitrate
      contamination.

PMID- 11226934
TI  - [The risk of malaria transmission by blood transfusion at Cotonou, Benin].
AB  - The risk of transmission of infectious agents by blood transfusion is a permanent
      preoccupation for diseases that we do not know how to cure, such as hepatitis B,
      hepatitis C and AIDS. However, few studies have been carried out concerning the
      risks of transmitting curable infectious diseases, such as malaria. We carried
      out a cross-sectional study of 355 healthy blood donors in the rainy season, in
      which we used thick and thin blood film smears to screen for malaria. We found
      that 33.5% of donors harbored trophozoites and were therefore capable of
      transmitting malaria via blood donation. There were 1,000 to 4,760 parasites per
      microliter of blood and there was no relationship between the load of parasitized
      red blood cells and clinical malaria. Plasmodium falciparum was the most common
      species identified (96.63% of cases). The results confirm that it is vital, in
      this age of resistance to anti-malaria drugs and HIV, to screen blood donations
      systematically. Patients receiving transfusions should be given anti-malaria
      treatment and donors should be encouraged to sleep under treated mosquito nets.

PMID- 11226935
TI  - [The effect of soccer training on the levels of atherosclerotic lipids in the
      blood of obese subjects].
AB  - Aerobic exercise may modify lipid levels in obese subjects. The resulting change
      in lipid profile reduces the risk of atherosclerosis. The aim of this study was
      to investigate the impact of soccer training on lipid parameters in obese
      individuals playing soccer for recreation. Thirty obese subjects aged 25 to 55
      years participated in the study. Twenty-two of the subjects played soccer
      recreationally for two hours per week over a four-month period and the remaining
      eight constituted the control group. Before and after the study period, we
      collected anthropometric data and capillary blood samples for the analysis of
      lipid parameters. All subjects had mixed obesity and lipid parameters showed that
      all were at risk of cardiovascular disease. The lipid profiles of the individuals
      in the training group did not become less atherosclerotic. Thus, soccer training
      without intensive coaching did not affect the weight or lipid profiles of these
      obese recreational soccer players. Such training is therefore less effective than
      appropriate therapeutic agents for reducing the risk of atherosclerosis in obese
      subjects. We suggest that regular individual aerobic exercise associated with
      dietetic advice is probably the best way to manage the risks of atherosclerosis.

PMID- 11226936
TI  - [Analysis of transfers in the Gynecology and Obstetrics Department of Bangui
      Hospital].
AB  - During a study carried out over twelve months in the National Reference Center
      for Gynecology and Obstetrics at Bangui Hospital, we recorded 1,369 cases of
      evacuation in a total 5,020 admissions to the department. This corresponds to a
      frequency of 27.3%. In 73.8% of cases, this intervention was performed for
      obstetric reasons. It was justified in 73.1% of cases, and 96.5% of the justified
      interventions were for obstetric reasons. The unjustified interventions led to a
      normal delivery in 97% of cases. Errors in diagnosis were detected in 16.5% of
      the cases. In terms of prognosis, we recorded 91 deaths in the perinatal period
      (96 per thousand live births) and 37 maternal deaths (of the 39 recorded in the
      department), accounting for 94.9% of all maternal deaths, with a mortality rate
      of 2.7% for women undergoing uterine evacuation. Infant mortality was higher in
      cases of late intervention. The most frequent causes of death of the mothers were
      hemorrhagia on delivery, severe infection, rupture of the uterus and the tearing
      of soft tissues.

PMID- 11226937
TI  - [Survey of infant mortality in Mirebalais, Haiti].
AB  - Infant mortality remains high in Haiti, at 74 deaths per 1,000 live births. In
      this study, we aimed to assess infant mortality in Mirebalais and to identify the
      associated risk factors. We carried out a census of pregnant women in Mirebalais,
      at the beginning of the study, over a three-week period. Twelve researchers
      visited the homes of the newborns to enroll the families in the study and to
      collect demographic data. Further visits were scheduled for two, four, six, nine
      and twelve months after birth. If the child died during this time, the
      investigator asked the mother about all the steps taken to prevent the death of
      the child, and an autopsy was carried out. The survey began on July 12 1994 and
      ended on December 31 1995. During that time, about 2,151 pregnant women were
      enrolled. Seven of these women died and 16 had abortions. In total, 2,069
      children were born to the enrolled women. We enrolled 515 other children after
      birth or following referral by health workers or midwives. We therefore followed
      2,584 children. We found that 10% of the mothers were aged between 15 and 19
      years, 66.3% had had one to three pregnancies and 73% were entirely uneducated.
      The early neonatal mortality rate was 4.64 per 1,000 live births, late neonatal
      mortality was 6.96 per thousand and post-neonatal mortality was 45.6 per thousand
      live births. Diarrhea was responsible for 60% of the deaths and acute respiratory
      infections for 11%, these two causes accounting for 71% of the deaths of children
      aged 1 to 12 months. Thus, although infant mortality has decreased it remains
      high in Mirebalais, largely due to diarrhea and acute respiratory infections in
      the post-neonatal period.

PMID- 11226938
TI  - [Evaluation in test huts of the protective effects of untreated mosquito nets
      against Anopheles gambiae s.s. bites].
AB  - The protection against insect bites afforded by untreated mosquito bed nets was
      studied at the field stations of Yaokoffikro and M'be in Ivory Coast. We tested
      damaged mosquito nets (tear holes covering 0.8% of the total area) in
      Yaokoffikro, undamaged mosquito nets and huts without mosquito nets in M'be. The
      blood feeding rate of Anopheles gambiae was 70% lower in huts with undamaged
      mosquito nets than in huts with no mosquito net or a damaged mosquito net. The
      natural exophilic behavior of the mosquito was increased and mosquito mortality
      reached 7.4%. The blood feeding rate of An. gambiae was 83% in huts with no
      mosquito net and 68% in huts with damaged mosquito nets. Exophilic behavior was
      normal (25%) and overall mortality was 5%. Immediate mortality of An. gambiae was
      54% with undamaged mosquito nets and only 17% in huts with no mosquito net. This
      difference may reflect the state of nutrition of the mosquitoes: 86% of the dead
      mosquitoes found in huts with undamaged mosquito nets had not fed, versus only
      24% in huts with no mosquito net. The unfed mosquitoes may be considered to have
      died from starvation. Intact mosquito nets conferred some protection against An.
      gambiae. This protection was not total but was "better than nothing", with 25% of
      mosquitoes blood feeding effectively even in the presence of an intact mosquito
      net. This protection reduces the probability of survival of the females. In
      contrast, torn mosquito nets trap the mosquitoes that enter, then allowing more
      than two thirds of the mosquitoes to take a blood meal on the sleeper.

PMID- 11226939
TI  - [Maternal complications of cesarean section: retrospective analysis of 3,231
      interventions at the Casablanca University Hospital, Morocco].
AB  - We carried out a retrospective analysis of 3,231 cases of cesarean section
      between 1994 and 1997, to assess the maternal mortality and morbidity associated
      with this intervention. The frequency of cesarean delivery was 12.4%. The
      indications for cesarean section were of three types: elective indications (627
      cases, 19.4%), emergency indications (454 cases, 14.1%), failure of normal labor
      (2,150 cases, 66.5%). Nine maternal deaths were noted (2.8 per thousand), one of
      which was directly linked to surgery. The peroperative complications were
      primarily major hemorrhagia (39 cases, 1.2%), visceral lesions such as bladder
      rupture (3 cases, 0.1%) and intestinal lesions (3 cases, 0.1%). Postoperative
      morbidity was predominated by infectious complications, particularly endometritis
      (5.1%). Thromboembolism was reported in 7 cases (0.2%). Cesarean section is used
      to preserve the life of both the mother and the child. However, maternal
      morbidity and mortality rates are higher with cesarean section than with vaginal
      delivery and therefore its indications must be justified.

PMID- 11226940
TI  - [Antimalarial drugs and their ways to use in the African milieu].
AB  - In the tropical African environment, malaria is both a major public health
      problem and a problem of socioeconomic development. It is caused by various
      agents, the most virulent and only lethal one of which is Plasmodium falciparum.
      This parasite is controlled by the appropriate use of antimalarial drugs and
      methods of individual and collective protection. The principal drugs used to
      treat bouts of malaria without vomiting caused by P. falciparum are amino-4
      quinoleines, essentially chloroquine. This is based on the level of resistance of
      P. falciparum to drugs in most African countries, particularly those of Central
      and West Africa. Malawi is the only country of southern Africa to have replaced
      chloroquine by sulfadoxine-pyrimethamine for this indication, in 1993. In cases
      of bouts of benign malaria with vomiting, but that are not serious, and severe
      malaria caused by P. falciparum (suspected or confirmed) with or without drug
      resistance, quinine should be given intravenously for at least three days. Once
      the patient regains consciouness or the digestive problems cease, quinine
      treatment should be given orally for 5 to 7 days. Sulfadoxine-pyrimethamine can
      be given as an alternative to quinine. The other antimalarial drugs currently on
      the African market (halofantrine, mefloquine, artemisinine and its derivatives)
      are often used inappropriately and should be used only in exceptional cases of
      severe bouts of complicated P. falciparum malaria, with suspected or confirmed
      resistance to amino-4-quinoleines. Individual protection against the Anopheles
      mosquito, the principal vector of malaria in Africa, is based largely on the use
      of mosquito nets impregnated with pyrethroid insecticide and the use of aerosols.
      Collective protection involves essentially environment-based measures.

PMID- 11226941
TI  - [Abdominal pregnancy].

PMID- 11226942
TI  - Evidence, outcomes, and common sense.

PMID- 11226943
TI  - Role of routine panendoscopy in cancer of the upper aerodigestive tract.
AB  - Patients with squamous cell carcinoma of the aerodigestive tract routinely
      undergo panendoscopy to detect possible synchronous second primary tumors. The
      aim of our study was to assess the incidence of synchronous and metachronous
      second primary tumors and to refine the role of panendoscopy. The charts of 358
      patients evaluated by means of panendoscopy during work-up of a first primary
      squamous cell carcinoma of the upper aerodigestive tract were reviewed. The
      incidence of a second primary tumor was 16.2%, with 6.4% being synchronous and
      9.8% being metachronous. In only 3.1% of all patients, a synchronous tumor was
      clinically silent and only revealed by means of the panendoscopy. The synchronous
      tumors were mainly in the oral cavity, pharynx, or larynx (61%), whereas the
      metachronous tumors were most likely in the lung (57%). Despite the low incidence
      of synchronous second primary tumors, we still recommend panendoscopy for
      assessment of the primary tumor and as a training field for residents.

PMID- 11226944
TI  - Minimum speech test battery for postlingually deafened adult cochlear implant
      patients.

PMID- 11226945
TI  - MUC4 (sialomucin complex) expression in salivary gland tumors and squamous cell
      carcinoma of the upper aerodigestive tract.
AB  - OBJECTIVES: This study investigates MUC4 expression in normal squamous epithelia
      and squamous cell carcinoma (SCC) of the upper aerodigestive tract (UADT), and in
      salivary gland neoplasms. STUDY DESIGN: MUC4 antigens in tumor and adjacent
      normal tissue are localized by immunocytochemical studies. Fresh frozen tissues
      from surgical resection specimens are further analyzed by Western blot. RESULTS:
      MUC4 is identified by immunocytochemical staining throughout the normal UADT
      mucosa, in 34 of 40 primary UADT SCC, and in 11 of 12 metastatic cervical lymph
      nodes. A trend toward decreased MUC4 staining in moderately and poorly
      differentiated tumors is noted. Immunoblots show MUC4 in 4 of 5 SCC analyzed.
      Immunocytochemical staining of MUC4 in 13 major and minor salivary gland
      neoplasms reveal variable staining of normal and neoplastic tissue. MUC4 is
      demonstrated in immunoblots of normal parotid tissue and in the single parotid
      malignancy analyzed, but is not demonstrated in one minor salivary gland
      malignancy. These findings characterize normal UADT mucosal and salivary MUC4
      expression, and MUC4 expression in SCC of the UADT and in salivary gland tumors.
      SIGNIFICANCE: Correlation of MUC4 expression with clinical outcomes may establish
      MUC4 as a potential molecular prognostic marker for these tumors.

PMID- 11226946
TI  - Effect of interleukin-2 and selenium on the growth of squamous cell carcinoma
      cells.
AB  - OBJECTIVES: The objectives of this study were to determine whether the expression
      of the interleukin-2 (IL-2) receptors on squamous cell carcinoma cells can be
      enhanced in the presence of selenium (Se) and contribute to a greater retardation
      of tumor growth after locoregional therapy with IL-2. STUDY DESIGN: The growth of
      the cells was studied after in vitro or dietary supplementation with Se in a
      murine model. RESULTS: Treatment of established tumors in hosts supplemented with
      Se with peritumoral injections of IL-2 resulted in 50% reduction of tumor size,
      whereas treatment of early tumors resulted in 72.4% reduction. The effect was
      most likely related to a combination of enhanced immune responsiveness and
      enhanced IL-2 receptor expression on the tumor cells. CONCLUSIONS AND
      SIGNIFICANCE: The data suggested that local immunotherapy with IL-2 in hosts
      supplemented with Se may represent an effective modality of treatment for the
      prevention of recurrences at the site of conventionally treated primary tumors,
      including tumors that do not express IL-2 receptors.

PMID- 11226947
TI  - Characteristics of bony erosion in allergic fungal rhinosinusitis.
AB  - OBJECTIVES: Erosion of bone with or without extension of disease into adjacent
      anatomic spaces is observed among some patients with allergic fungal
      rhinosinusitis (AFRS). The objective of this report is to further define these
      findings as they relate to this disease. STUDY DESIGN: Retrospective chart review
      of 142 patients with AFRS diagnosed using the Bent-Kuhn criteria. All patients
      were treated at a single institution. RESULTS: Approximately 20% of patients with
      AFRS demonstrated bone erosion on CT scan. The ethmoid sinus was the most
      commonly eroded site. The orbit and anterior cranial fossa were the most common
      adjacent anatomic spaces to exhibit disease extension. Sinus expansion, not the
      specific organism identified, was associated with the presence of bone erosion.
      Surgical management with endoscopic techniques was successful for all patients
      without any major perioperative complications. CONCLUSION: Bone erosion can be
      related to AFR. Recognition of this possibility is important because bone erosion
      can be interpreted as an indication of invasive pathosis. In the presence of bone
      erosion or disease extension, endoscopic techniques can be used to surgically
      manage this disease.

PMID- 11226948
TI  - Financial support for research in otolaryngology.
AB  - OBJECTIVES: This project describes the use of computer-assisted searches of
      medical literature in an attempt to track the prevalence and type of funding of
      medical research. STUDY DESIGN AND SETTING: The study is a computer-assisted
      observational survey of the medical literature. To establish a database and track
      funding trends, a computer-assisted Medline search (CAMS) of the literature from
      1986 to 1991 and 1992 to August 1996 was undertaken for 3 areas of interest: (1)
      sources of support, (2) comparison with other specialties, and (3) the validity
      of CAMS. A journal-based search examined the field of otolaryngology, which
      includes all the head and neck related sciences, and an institution-based search
      examined the clinical specialty of otolaryngology. RESULTS: By selected journal
      search, the field of otolaryngology has about one-third funding (34% of 20,751
      papers), and about one-half of that is supported by the National Institutes of
      Health. This proportion of federal support increased over time. By institution
      line search, the specialty of otolaryngology is less well funded (26% of 15,480
      papers) as might be expected. However, in contrast to basic sciences, there is a
      trend of decreased funding over the 11-year period of the study. SIGNIFICANCE: It
      appears that while the field of otolaryngology (basic scientists and clinicians)
      may be enjoying increasing support of research, the clinical specialty of
      otolaryngology is among the many specialties that exhibit a trend of decreasing
      level of NIH support. CONCLUSIONS: Computer-assisted surveys are an effective
      method of tracking funding for research in otolaryngology and other specialties.
      CAMS may be a valuable tool for monitoring efforts to improve funding resources
      for otolaryngology.

PMID- 11226949
TI  - Computed tomography imaging of the maxillary and ethmoid sinuses in children with
      short-duration purulent rhinorrhea.
AB  - INTRODUCTION: Adults with a common cold often have paranasal sinus effusions
      detected by computed tomographic (CT) scans. There are no comparable data for
      children. The purpose of this study was to document the sinus CT findings in
      children with short-duration purulent rhinorrhea. DESIGN: Thirty children, 3 to
      12 years of age (median age, 7 years), with purulent rhinorrhea for a mean
      duration of 5 days (and always less than 9 days) were enrolled in the study. The
      children were otherwise well. Institutional Review Board (IRB)-approval was
      obtained before enrollment of the first patient. Informed written consent was
      obtained from each child's parent. CT imaging of the maxillary and ethmoid
      sinuses was obtained on the day of the initial visit (occasionally, the following
      day). Follow-up CT scans were obtained from cooperative children/parents, 3 to 4
      weeks later. RESULTS: Opacification or an air/fluid level in the maxillary
      sinuses was seen in 27 (90%) of 30 study children at study entry. Ethmoid sinuses
      were not opacified without opacification of a maxillary sinus. Three weeks later,
      24 of 27 study children, who had positive CT scans on study entry, improved
      clinically. Of 17 follow-up CT scans, 10 (58%) normalized, 4 had improvement of
      bilateral disease, and 3 improved with unilateral disease. None appeared worse
      than baseline. CONCLUSIONS: Pansinus opacification (ethmoid and maxillary
      sinuses), on CT scans in children with short-duration purulent nasal drainage was
      seen in 70% of children. An additional 20% had isolated maxillary sinus effusions
      (10% had no effusion). Three-week follow-up CT scans on 17 children were normal
      in 60% and improved (partial clearance) in 40%. In this patient population, the
      decision to treat with antibiotics should be made on clinical grounds alone.

PMID- 11226950
TI  - Tongue lesions in the pediatric population.
AB  - OBJECTIVE: To describe the spectrum of pediatric tongue lesions treated
      surgically at Columbia-Presbyterian Medical Center from January 1990 to December
      1999. STUDY DESIGN AND SETTING: Retrospective case-series at the pediatric
      hospital of a tertiary care, academic medical center. RESULTS: Seventeen patients
      were identified. Their ages ranged from 1 to 132 months (median, 7 months). Eight
      lesions were located anteriorly: mucous cyst (1), polyp (1), chronic inflammatory
      mass (1), hamartoma (1), squamous papilloma (2), cavernous hemangioma (1), and
      vascular malformation (1). Four lesions were located posteriorly: teratoma (1),
      glial choristoma (1), osseous choristoma (1), and benign epithelial cyst (1).
      Finally, there were 5 diffuse lesions including macroglossia (4) and massively
      infiltrating congenital lymphatic malformation (1). Symptoms included respiratory
      distress (3) and dysarthria (3); all other children were asymptomatic.
      CONCLUSIONS: This series revealed an interesting spectrum of rare solid tumors;
      compared with other large series, fewer lymphatic and vascular malformations were
      seen. Presenting symptoms, differential diagnosis, and surgical approach were
      differentiated according to lesion location.

PMID- 11226951
TI  - Subcutaneous cervicofacial and mediastinal emphysema after dental
      instrumentation.

PMID- 11226952
TI  - Cannula aspiration of peritonsillar abscesses.
AB  - Peritonsillar abscesses may be treated by needle aspiration, incision and
      drainage, or abscess tonsillectomy. A modification of the technique of needle
      aspiration is described. This technique minimizes the risk of vascular damage
      during needle aspiration and is more reassuring to the patient.

PMID- 11226953
TI  - Rathke's cleft cyst presenting as sphenoid sinusitis.
AB  - Rathke's cleft cysts are developmental abnormalities of the craniopharyngeal duct
      composed of retained stratified ciliated cuboidal cells of the respiratory type.
      Incidentally found in the pars intermedia in 13% to 33% of routine autopsies,
      they are discovered in growing numbers on CT and MRI scans. From 1991 to 1999, 9
      cases of Rathke's cleft cysts were encountered by the senior authors, 4 of which
      were treated surgically (3 by using a transsphenoidal approach and one by using a
      transcranial subfrontal approach). Of the 3 patients treated with a
      transsphenoidal approach, 2 presented with symptoms mimicking sphenoid sinusitis
      and were initially referred for otolaryngologic evaluation. The clinical,
      pathologic, and radiologic features, as well as management and follow-up of those
      2 patients, are reviewed. There has been only one previous case report of
      Rathke's cleft cysts presenting as sinusitis. Nevertheless, the otolaryngologist
      should be aware of this condition because it may present with other significant
      symptomatic extracranial extensions.

PMID- 11226954
TI  - Efficacy of selective neck dissection: a review of 503 cases of elective and
      therapeutic treatment of the neck in squamous cell carcinoma of the upper
      aerodigestive tract.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy of selective
      neck dissection (SND) in elective and therapeutic treatment of the neck. METHODS:
      A retrospective review was undertaken of 503 previously untreated patients
      undergoing 711 SNDs as a part of initial therapy for squamous cell carcinoma of
      the larynx, oral cavity, oropharynx, and hypopharynx from August 1986 to June
      1997 at a single institution. Lymph nodes were pathologically negative in 249 and
      positive in 254 patients. Postoperative radiotherapy was given to 14.5% of the
      node-negative and 62.2% of the node-positive patients. The median follow-up
      interval was 41 months. RESULTS: The 3-year regional recurrence rates estimated
      according to Kaplan-Meier were as follows: pN0, 4.7%; pN1, 4.9%; pN2, 12.1%. A
      comparison of recurrence rates with respect to the extent of neck disease and
      postoperative radiotherapy demonstrated a tendency to an improved regional
      control in irradiated patients with one metastasis and a distinctly improved
      regional control in patients with multiple metastases or metastases with
      extracapsular spread. CONCLUSION: The results achieved with SND compare favorably
      with the results reported for modified radical neck dissection. The application
      of SND might be extended to more advanced neck disease.

PMID- 11226955
TI  - Lymphoid cell infiltration into Epstein-Barr virus-positive nasopharyngeal
      carcinomas.
AB  - OBJECTIVES: A pilot study was designed to analyze lymphoid cell infiltration in
      Epstein-Barr virus-positive (EBV+) nasopharyngeal carcinomas (NPCs) and to
      determine whether this pattern of infiltration is consistent with non-EBV+ head
      and neck carcinomas or with solid EBV+ tumors in other locations. STUDY DESIGN:
      We performed a retrospective analysis of archived NPCs and oral cavity
      carcinomas. METHODS: Immunohistochemical staining of the archive material for
      various markers (CD3, CD8, UCHL-1, S-100, and intercellular adhesion molecule)
      was performed. Polymerase chain reaction techniques to establish the presence of
      the EBV genome were used. Cells in different locations were counted under a light
      microscope by 2 of the authors. RESULTS: The infiltration pattern of NPCs was
      different from that of oral cavity carcinomas. Stromal infiltration was
      significantly denser in oral cavity carcinomas. Tumor nest infiltration was more
      pronounced in NPCs. The pattern of infiltration was comparable with what has been
      described for other solid EBV+ tumors. CONCLUSIONS: The immune response to NPCs
      is likely to be strongly influenced by the presence of the EBV genome. The
      pattern of infiltration is similar to that of other non-head and neck EBV+ solid
      tumors and different from that of EBV- head and neck carcinomas.

PMID- 11226956
TI  - Management of cancer of the supraglottis.
AB  - We present the results of a retrospective study of 903 patients treated with
      conservation surgery for carcinoma of the supraglottic larynx so we can evaluate
      our management of supraglottic cancer with different types of surgery. In 301
      patients, an extended supraglottic laryngectomy was performed. The recent
      selective use of transoral laser resection appears to be a rational approach. The
      5-year uncorrected survival was 84%, 81%, 76%, and 55% for stages I, II, III, and
      IV, respectively. The most common site for local-regional failure was the
      cervical lymphatics. The percentage of occult disease in the NO neck was 21% and
      epilaryngeal supraglottic location, locally advanced and GIII tumors have a
      higher frequency of lymph node involvement. There were no differences between
      comprehensive and anterolateral elective neck dissections. A bilateral elective
      neck dissection is recommended. In histologically positive neck disease, the
      survival rates were better with postoperative radiotherapy only in cases of
      extracapsular spread.

PMID- 11226957
TI  - Altered MUC1 and MUC2 glycoprotein expression in laryngeal cancer.
AB  - The purpose of this study was to determine whether mucin expression is altered in
      laryngeal cancer. MUC1 and MUC2 mucin expression was examined in biopsy specimens
      from 80 patients that comprised 23 laryngeal dysplasias, 36 laryngeal carcinomas,
      and 21 normal larynx control specimens. High MUC1 expression was found in all 3
      groups (P = 0.689, Fisher exact test). However, significantly higher levels of
      MUC2 expression were detected in carcinomas compared with dysplasias and control
      specimens (P = 0.009, Fisher exact test). Altered MUC2 expression may be an
      important step in carcinogenesis in laryngeal cancer.

PMID- 11226958
TI  - Continuous intratympanic infusion of gentamicin via a microcatheter in Meniere's
      disease.
AB  - Between 1995 and 1998, 11 patients with disabling Meniere's disease were treated
      at our institution with a continuous gentamicin infusion into the middle ear via
      a microcatheter. The patients had frequent attacks of vertigo and vomiting
      (functional levels 3-5). Hearing threshold on the affected side was significantly
      worse than on the healthy side (stage 4+5). Gentamicin was applied by a high
      precision insulin pump with a flow rate of 40 mg per day directly in front of the
      round window. Application was stopped as soon as signs of vestibular affection
      appeared. A good overall control of vertiginous spells was achieved in 8
      patients. Eight patients experienced complete hearing loss on the affected side,
      1 experienced a slight worsening, and 1 had no hearing change. There was no
      correlation between the cumulative gentamicin dosage and the hearing loss. Our
      findings show that in terms of hearing loss and hospitalization time the
      continuous gentamicin application is inferior to other applications presented in
      the literature.

PMID- 11226959
TI  - Auricular pseudocysts: a treatment with the Chulalongkorn University vacuum
      device.
AB  - Auricular pseudocysts are rare lesions that present as an asymptomatic cystic
      swelling of the anterior surface of the auricle, particularly the antihelix.
      Typically, the pseudocysts contain viscous straw-yellow fluid similar in
      appearance to olive oil; however, a clear pale yellow serous transudate may also
      be encountered. Various therapeutic approaches have been used with variable
      success. We describe a simple small vacuum device called the Chulalongkorn
      University vacuum device, which was developed in our center. The device can be
      easily made anywhere by any surgeon. We report the outcome in 17 patients treated
      by means of needle aspiration plus application of the Chulalongkorn University
      vacuum device for 5 days. A complete resolution of the lesion was obtained in 15
      (88.2%) patients. Because the procedure is safe and effective and does not
      require an operating room setting, it may be accepted as an option in the
      treatment of auricular pseudocysts.

PMID- 11226960
TI  - Intracranial metastases in patients with squamous cell carcinoma of the head and
      neck.
AB  - BACKGROUND: Intracranial metastases are rarely clinically diagnosed in patients
      with head and neck squamous cell carcinoma. Only 7 patients with metastases to
      the cavernous sinus from head and neck squamous cell carcinomas have been
      reported. METHODS: A retrospective study revealed 13 patients with intracranial
      metastases of head and neck squamous cell carcinoma. In a 53-year-old woman a
      cavernous sinus metastasis of a laryngeal carcinoma was histologically diagnosed
      by using a CT-guided surgical navigation system and was treated with stereotactic
      radiotherapy. RESULTS: The mean survival was 4.3 months. Predictive factors for
      longer survival were absence of extracranial disease, age younger than 60 years,
      and treatment with radiotherapy. CONCLUSIONS: The prognosis for patients with
      intracranial disease is poor. The current development of computer-assisted
      stereotactic navigation and stereotactic radiotherapy may facilitate surgical
      diagnostic exploration and improve treatment, especially in patients without
      extracranial disease.

PMID- 11226961
TI  - Is carotid reconstruction for advanced cancer in the neck a safe procedure?
AB  - Head and neck surgeons hesitate to resect the carotid artery because of the
      postoperative risk of neurologic sequelae. On the other hand, there is no
      curative therapeutic option for head and neck cancer involving the carotid
      artery, except for complete tumor removal. A retrospective review of all
      published articles in the English literature dealing with carotid reconstruction
      for head and neck cancer from 1987 to 1998 was performed. There were only 11
      articles, including our series, that reported outcomes of this procedure. Among
      the 148 patients of this series, major neuromorbidity was 4.7%, and mortality
      occurred in 6.8% of the patients. Combined major neuromorbidity and mortality was
      10.1%. Because total removal of the advanced cancer is the only therapy that can
      offer the patients a chance for cure, head and neck surgeons should aggressively
      perform carotid resection and reconstruction.

PMID- 11226962
TI  - Relationship between the size of neopharynx after laryngectomy and long-term
      swallowing function: an assessment by scintigraphy.
AB  - OBJECTIVES: To study the relationship between the size of neopharynx after total
      laryngectomy and long-term swallowing function by means of scintigraphy. STUDY
      DESIGN: The width of pharyngeal remnant was measured during surgery in 11
      patients. Their swallowing function was assessed by scintigraphy 8 to 10 years
      after surgery. METHODS: The width of pharyngeal remnant at its narrowest point in
      both relaxed and stretched state was measured during surgery. Postoperative
      scintigraphy data on swallowing were obtained and computed along 3 lines, (1)
      transit time through neopharynx, (2) percentage of bolus transferred, and (3)
      swallowing efficiency. The relationship between the 2 sets of data was analyzed
      by linear regression analysis. RESULTS: (1) No statistically significant
      relationship was found between the size of neopharynx and swallowing function.
      (2) All patients are clinically asymptomatic. CONCLUSIONS: The swallowing
      function is not affected by the size of the neopharynx in 11 patients with
      pharyngeal remnant width ranging from 3 to 8 cm (stretched).

PMID- 11226963
TI  - Intrasaccular detachable platinum coil embolization for traumatic pseudoaneurysm
      treatment of a cavernous carotid artery.

PMID- 11226964
TI  - Growing cribiform plate fracture in a young adult patient: a case report.

PMID- 11226965
TI  - Unilateral deafness with persistent otoacoustic emissions after neurosurgical
      removal of a cerebellar astrocytoma.

PMID- 11226966
TI  - Ascher syndrome.

PMID- 11226967
TI  - Vestibular toxicity is unproven as the cause of Gulf War syndrome.

PMID- 11226969
TI  - Incidence of transitional cell carcinoma and arsenic in drinking water: a follow
      up study of 8,102 residents in an arseniasis-endemic area in northeastern Taiwan.
AB  - A significant association between ingested arsenic and bladder cancer has been
      reported in an arseniasis-endemic area in southwestern Taiwan, where many
      households share only a few wells in their villages. In another arseniasis
      endemic area in northeastern Taiwan, each household has its own well for
      obtaining drinking water. In 1991-1994, the authors examined risk of transitional
      cell carcinoma (TCC) in relation to ingested arsenic in a cohort of 8,102
      residents in northeastern Taiwan. Estimation of each study subject's individual
      exposure to inorganic arsenic was based on the arsenic concentration in his or
      her own well water, which was determined by hydride generation combined with
      atomic absorption spectrometry. Information on duration of consumption of the
      well water was obtained through standardized questionnaire interviews. The
      occurrence of urinary tract cancers was ascertained by follow-up interview and by
      data linkage with community hospital records, the national death certification
      profile, and the cancer registry profile. Cox proportional hazards regression
      analysis was used to estimate multivariate-adjusted relative risks and 95%
      confidence intervals. There was a significantly increased incidence of urinary
      cancers for the study cohort compared with the general population in Taiwan
      (standardized incidence ratio = 2.05; 95% confidence interval (CI): 1.22, 3.24).
      A significant dose-response relation between risk of cancers of the urinary
      organs, especially TCC, and indices of arsenic exposure was observed after
      adjustment for age, sex, and cigarette smoking. The multivariate-adjusted
      relative risks of developing TCC were 1.9, 8.2, and 15.3 for arsenic
      concentrations of 10.1-50.0, 50.1-100, and >100 microg/liter, respectively,
      compared with the referent level of < or =10.0 microg/liter.

PMID- 11226971
TI  - Multivariate logistic regression for familial aggregation of two disorders. I.
      Development of models and methods.
AB  - The question of whether two disorders cluster together, or coaggregate, within
      families often arises. This paper considers how to analyze familial aggregation
      of two disorders and presents two multivariate logistic regression methods that
      model both disorder outcomes simultaneously. The first, a proband predictive
      model, predicts a relative's outcomes (the presence or absence of each of the two
      disorders) by using the proband's disorder status. The second, a family
      predictive model derived from the quadratic exponential model, predicts a family
      member's outcomes by using all of the remaining family members' disorder
      statuses. The models are more realistic, flexible, and powerful than univariate
      models. Methods for estimation and testing account for the correlation of
      outcomes among family members and can be implemented by using commercial
      software.

PMID- 11226972
TI  - Invited commentary: arsenic and cancer of the urinary tract.
AB  - Inorganic arsenic in drinking water is a recognized cause of cancers of the skin,
      lung, and bladder. In the absence of an animal model for studying arsenic
      carcinogenesis, epidemiologic studies provide the only quantitative data for
      guiding risk assessment at levels that commonly occur in drinking water. To date,
      most estimates of risk at low and moderate levels of exposure (<200 microg/liter)
      have been based on extrapolation from ecologic studies of populations exposed to
      much higher levels. Epidemiologic data from the prospective cohort study by Chiou
      et al. that appears in this issue of the JOURNAL: (Am J Epidemiol 2001;153:411
      18) make an important contribution to improving the precision of the estimated
      risk of transitional cell carcinoma of the urinary tract associated with ingested
      arsenic from drinking water. The great strength of the study derives from having
      individually based measures of exposure and cancer diagnoses. Arsenic in water is
      a topic of great concern and controversy, and epidemiologic studies will continue
      to provide crucial information about the risks of cancer and other diseases
      associated with ingested arsenic.

PMID- 11226974
TI  - Lutein and zeaxanthin in the diet and serum and their relation to age-related
      maculopathy in the third national health and nutrition examination survey.
AB  - Relations of the carotenoids lutein and zeaxanthin in the diet and serum to
      photographic evidence of early and late age-related maculopathy (ARM) among
      persons over age 40 years (n = 8,222) were examined. Inverse relations of these
      carotenoids in the diet or serum to any form of ARM were not observed overall.
      There was a direct relation of dietary levels to one type of early ARM (soft
      drusen). However, relations differed by age and race. In the youngest age groups
      who were at risk for developing early (ages 40-59 years) or late (ages 60-79
      years) ARM, higher levels of lutein and zeaxanthin in the diet were related to
      lower odds for pigmentary abnormalities, one sign of early ARM (odds ratio among
      persons in high vs. low quintiles = 0.1, 95 percent confidence interval: 0.1,
      0.3) and of late ARM (odds ratio = 0.1, 95 percent confidence interval: 0.0, 0.9)
      after adjustment for age, gender, alcohol use, hypertension, smoking, and body
      mass index. Relations of these carotenoids to ARM may be influenced by age and
      race and require further evaluation in separate populations and in prospective
      studies.

PMID- 11226975
TI  - Air pollution from traffic at the residence of children with cancer.
AB  - The hypothesis that exposure to traffic-related air pollution increases the risk
      of developing cancer during childhood was investigated. The authors enrolled
      1,989 children reported to the Danish Cancer Registry with a diagnosis of
      leukemia, tumor of the central nervous system, or malignant lymphoma during 1968
      1991 and 5,506 control children selected at random from the entire childhood
      population. The residential histories of the children were traced from 9 months
      before birth until the time of diagnosis of the cases and a similar period for
      the controls. For each of the 18,440 identified addresses, information on traffic
      and the configuration of streets and buildings was collected. Average
      concentrations of benzene and nitrogen dioxide (indicators of traffic-related air
      pollution) were calculated for the relevant period, and exposures to air
      pollution during pregnancy and during childhood were calculated separately. The
      risks of leukemia, central nervous system tumors, and all selected cancers
      combined were not linked to exposure to benzene or nitrogen dioxide during either
      period. The risk of lymphomas increased by 25% (p for trend = 0.06) and 51% (p
      for trend = 0.05) for a doubling of the concentration of benzene and nitrogen
      dioxide, respectively, during the pregnancy. The association was restricted to
      Hodgkin's disease.

PMID- 11226976
TI  - Association between ozone and hospitalization for acute respiratory diseases in
      children less than 2 years of age.
AB  - To clarify the health effects of ozone exposure in young children, the authors
      studied the association between air pollution and hospital admissions for acute
      respiratory problems in children less than 2 years of age during the 15-year
      period from 1980 to 1994 in Toronto, Canada. The daily time series of admissions
      was adjusted for the influences of day of the week, season, and weather. A 35%
      (95% confidence interval: 19%, 52%) increase in the daily hospitalization rate
      for respiratory problems was associated with a 5-day moving average of the daily
      1-hour maximum ozone concentration of 45 parts per billion, the May-August
      average value. The ozone effect persisted after adjustment for other ambient air
      pollutants or weather variables. Ozone was not associated with hospital
      admissions during the September-April period. Ambient ozone levels in the
      summertime should be considered a risk factor for respiratory problems in
      children less than 2 years of age.

PMID- 11226977
TI  - Associations of blood lead, dimercaptosuccinic acid-chelatable lead, and tibia
      lead with neurobehavioral test scores in South Korean lead workers.
AB  - The authors performed a cross-sectional study to evaluate associations between
      blood lead, tibia lead, and dimercaptosuccinic acid (DMSA)-chelatable lead and
      measures of neurobehavioral and peripheral nervous system function among 803 lead
      exposed workers and 135 unexposed controls in South Korea. The workers and
      controls were enrolled in the study between October 1997 and August 1999. Central
      nervous system function was assessed with a modified version of the World Health
      Organization Neurobehavioral Core Test Battery. Peripheral nervous system
      function was assessed by measuring pinch and grip strength and peripheral
      vibration thresholds. After adjustment for covariates, the signs of the beta
      coefficients for blood lead were negative for 16 of the 19 tests and blood lead
      was a significant predictor of worse performance on eight tests. On average, for
      the eight tests that were significantly associated with blood lead levels, an
      increase in blood lead of 5 microg/dl was equivalent to an increase of 1.05 years
      in age. In contrast, after adjustment for covariates, tibia lead level was not
      associated with neurobehavioral test scores. Associations with DMSA-chelatable
      lead were similar to those for blood lead. In these currently exposed workers,
      blood lead was a better predictor of neurobehavioral performance than was tibia
      or DMSA-chelatable lead, mainly in the domains of executive abilities, manual
      dexterity, and peripheral motor strength.

PMID- 11226978
TI  - Forearm bone mineral density by age in 7,620 men and women: the Tromso study, a
      population-based study.
AB  - Population-based studies of adult forearm bone mineral density (BMD) by age are
      scarce, and standardized reference values are lacking. In this cross-sectional
      study, men aged 55-74 years, women aged 50-74 years, and representative 5-10%
      samples of remaining age groups between 25 and 84 years living in Tromso, Norway,
      were invited for forearm BMD measurement in 1994-1995. The authors measured 3,062
      men and 4,558 women (response rate, 78%) by single x-ray absoptiometry at distal
      and ultradistal forearm sites. Up to age 50, the mean BMD difference was -0.1%
      per 1-year age group in both sexes. After age 50, the mean BMD difference per 1
      year age group was -0.6% in men and -1.3% (distal) and -1.5% (ultradistal) in
      women. The BMD by age curve was linear for men throughout senescence, but women
      had a slope change to -0.7% (distal) and -0.8% (ultradistal) per 1-year age group
      from the 65- to 69-year age group. BMD levels and BMD by age association in the
      general population (n = 7,620) and in the population without bone-threatening
      diseases or medication (n = 5,179) were similar. Only longitudinal studies can
      clarify whether cohort effects or longitudinal BMD development patterns explain
      these cross-sectional results.

PMID- 11226979
TI  - Plasma folate, vitamin B(12), and homocyst(e)ine concentrations in preeclamptic
      and normotensive Peruvian women.
AB  - The authors measured maternal third trimester plasma folate, vitamin B(12), and
      homocyst(e)ine concentrations among 125 women with preeclampsia and 179
      normotensive women in Lima, Peru (1997-1998), to determine whether these analytes
      were associated with the occurrence of preeclampsia. Logistic regression
      procedures were used to calculate maximum likelihood estimates of odds ratios and
      95% confidence intervals. Relative to women in the upper quartile of the control
      distribution of maternal plasma folate concentrations, women with values in the
      lowest quartile experienced a 1.6-fold increased risk of preeclampsia (odds ratio
      = 1.6; 95% confidence interval: 0.8, 3.2). There was no evidence of an increased
      risk of preeclampsia associated with low plasma vitamin B(12) concentrations. The
      unadjusted relative risk of preeclampsia increased across successively higher
      quartiles of plasma homocyst(e)ine level (odds ratios were 1.0, 1.0, 1.5, and
      2.9, respectively, with the lowest quartile used as the referent; p for linear
      trend = 0.0004). After adjustment for maternal age, parity, gestational age, use
      of prenatal vitamins, whether the pregnancy had been planned, and educational
      attainment, the relative risk between extreme quartiles was 4.0 (95% confidence
      interval: 1.8, 8.9). These findings are consistent with earlier reports
      suggesting that hyperhomocyst(e)inemia in pregnancy may be a risk factor for
      preeclampsia.

PMID- 11226980
TI  - Metabolic syndrome and ischemic heart disease in elderly men and women.
AB  - Associations between metabolic syndrome components and prevalent ischemic heart
      disease (IHD) were investigated in a cross-sectional, community-based study of
      elderly men (n = 1,015) and women (n = 1,259) in Rancho Bernardo, California, in
      1984-1987. In both sexes, there were significant positive associations between
      IHD defined by resting electrocardiogram criteria and age, systolic blood
      pressure, fasting and postchallenge hyperglycemia, total cholesterol/high density
      lipoprotein cholesterol (HDL cholesterol) ratio, and triglycerides and an inverse
      significant association with HDL cholesterol. High collinearity and interactions
      between serum insulin and metabolic syndrome variables were accounted for by
      uncorrelated principal components identified by factor analysis. In both men and
      women, three uncorrelated principal components were identified, representing a
      central metabolic factor (body mass index, fasting and 2-hour serum insulin, high
      serum triglycerides, and low HDL cholesterol), a glucose factor, and a blood
      pressure factor. In a multivariate model with age and sex, all three factors were
      significantly associated with IHD by electrocardiogram criteria; central
      metabolic factor (odds ratio (OR) = 1.6, p = 0.001), glucose factor (OR = 1.4, p
      < 0.001), blood pressure factor (OR = 1.2, p = 0.005), age (10 years) (OR = 1.8,
      p < 0.001), and female sex (OR = 0.5, p < 0.02). Similar results were obtained in
      analyses using clinically manifest IHD as the outcome. These results support the
      thesis that the metabolic syndrome exerts effects through different risk factors
      by different mechanisms.

PMID- 11226981
TI  - Serum triglycerides and risk of coronary heart disease among Japanese men and
      women.
AB  - To examine the relation of triglycerides with coronary heart disease among
      populations with low mean total cholesterol, the authors conducted a 15.5-year
      prospective study ending in 1997 of 11,068 Japanese aged 40-69 years (4,452 men
      and 6,616 women with mean total cholesterol = 4.73 mmol/liter and 5.03
      mmol/liter, respectively), initially free of coronary heart disease or stroke.
      There were 236 coronary heart disease events comprising 133 myocardial
      infarctions, 68 angina pectoris events, and 44 sudden cardiac deaths. The
      coronary heart disease incidence was greater in a dose-response manner across
      increasing quartiles of nonfasting triglycerides for both sexes. The multivariate
      relative risk of coronary heart disease adjusting for coronary risk factors and
      time since last meal associated with a 1-mmol/liter increase in triglycerides was
      1.29 (95% confidence interval (CI): 1.09, 1.53; p = 0.004) for men and 1.42 (95%
      CI: 1.15, 1.75; p = 0.001) for women. The trend was similar for myocardial
      infarction, angina pectoris, and sudden cardiac death. The relation of
      triglycerides with coronary heart disease was not influenced materially by total
      cholesterol levels or, in a subsample analysis (51% of total sample), by high
      density lipoprotein cholesterol levels. Nonfasting serum triglycerides predict
      the incidence of coronary heart disease among Japanese men and women who possess
      low mean values of total cholesterol. Further adjustment for high density
      lipoprotein cholesterol suggests an independent role of triglycerides on the
      coronary heart disease risk.

PMID- 11226983
TI  - Multivariate logistic regression for familial aggregation of two disorders. II.
      Analysis of studies of eating and mood disorders.
AB  - Family studies have suggested that eating disorders and mood disorders may
      coaggregate within families. Previous studies, however, have been limited by use
      of univariate modeling techniques and failure to account for the correlation of
      observations within families. To provide a more efficient analysis and to
      illustrate multivariate logistic regression models for familial aggregation of
      two disorders, the authors analyzed pooled data from two previously published
      family studies (conducted in Massachusetts in 1984-1986 and 1986-1987) by using
      multivariate proband predictive and family predictive models. Both models
      demonstrated a significant familial aggregation of mood disorders and familial
      coaggregation of eating and mood disorders. The magnitude of the coaggregation
      between eating and mood disorders was similar to that of the aggregation of mood
      disorders. Similar results were obtained with alternative models, including a
      traditional univariate proband predictive model. In comparison with the
      univariate model, the multivariate models provided greater flexibility, improved
      precision, and wider generality for interpreting aggregation effects.

PMID- 11226984
TI  - The Halifax disaster of 1917 and the birth of North American pediatric surgery.

PMID- 11226985
TI  - Pediatric surgery advances into the university hospital.

PMID- 11226986
TI  - Pulsed Doppler sonography of the hilar renal artery: differentiation of
      obstructive from nonobstructive hydronephrosis in children.
AB  - BACKGROUND/PURPOSE: It is difficult to detect the arcuate or cortical renal
      arteries when performing pulsed Doppler sonography (PDS) for congenital
      hydronephrosis. This study was undergone to assess the usefulness of PDS of the
      hilar renal artery to differentiate obstructive from nonobstructive
      hydronephrosis. METHODS: The authors performed PDS of the hilar renal artery in
      80 normal children: 20 aged 0 to 1 months (group I), 20 aged 1 to 12 months
      (group II), 20 aged 1 to 6 years (group III), and 20 aged 7 to 15 years (group
      IV). Based on diuretic renography findings, 22 kidneys from 19 children with a
      ureteropelvic junction (UPJ) stricture were divided into 7 dilated obstructed and
      15 dilated nonobstructed kidneys. The peak-systolic velocity (PSV), end-diastolic
      velocity (EDV), mean average velocity (Vm) and the resistive index (RI = [PSV -
      EDV]/PSV) were measured at the hilar renal artery. RESULTS: There was a
      significant difference in the RI of the hilar renal artery between obstructive
      and nonobstructive hydronephrosis. CONCLUSION: A pulsed Doppler evaluation of the
      hilar renal artery is useful for detecting an obstructive UPJ stricture compared
      with assessing arcuate or cortical renal arteries.

PMID- 11226987
TI  - Penoplasty for buried penis in children: report of 50 cases.
AB  - PURPOSE: The authors report their experience with a large number of children with
      buried penis and describe their surgical technique. METHODS: Fifty consecutive
      cases of buried penis that occurred between 1993 and 1999 were analyzed by chart
      review. Age at the time of surgery was 11 months to 13 years. Each patient
      underwent elective surgical repair utilizing a surgical technique not described
      previously. The authors' technique avoids a circumferential incision at the base
      of the penis, decreasing postoperative edema. The authors also utilize a unique
      through and through vertical mattress suture at the base of the penis that firmly
      attaches the shaft skin to the underlying corpora. RESULTS: All patients had a
      good to excellent outcome with a low postoperative complication rate. One patient
      fell during the postoperative period and developed a wound dehiscence. Early in
      the series 3 patients underwent additional procedures for recurrent retraction
      (6%). All patients experienced some postoperative discomfort as expected. Edema,
      when present, was mild and resolved within an acceptable period of time. All
      patients had a good cosmetic result with increased visualization of the penile
      shaft. CONCLUSIONS: A surgical approach to the buried penis is warranted in most
      circumstances. There are psychological benefits to both the patients and the
      parents. Although the authors perform the procedure as early as 11 months, it can
      be performed safely at 3 months. The procedure reported here provides immediate
      excellent cosmetic results with a low complication rate. The authors do not
      recommend suprapubic lipectomy either alone or in combination with the buried
      penis procedure. Circumcision should be avoided in an infant with a definite
      diagnosis of buried penis.

PMID- 11226988
TI  - Surgical correction of buried penis: a review of 60 cases.
AB  - BACKGROUND/PURPOSE: The authors reviewed 60 cases of buried penis, treated in a
      single institution with postoperative follow-up for at least 6 months. The review
      was aimed at providing information that might help to optimize the results in
      future surgical correction of this uncommon, but not rare, congenital disorder.
      METHODS: From January 1, 1989 to December 31, 1998, 62 boys with buried penis
      were treated with 1 of the following procedures: group 1A (n = 6), preputial
      unfurling alone; group 1B (n = 8), modified preputial unfurling; group 1C (n =
      12), penoplasty devised by the first author with preservation of the preputial
      skin; and group 2 (n = 36), penoplasty with trimming of the inner preputial skin.
      Postoperative follow-up of more than 6 months after operation was achieved in 60
      of 62 patients for a total of 25 patients in group 1 (A through C) and 35
      patients in group 2. RESULTS: Recurrent buried penis developed in 8 of 60
      patients (13%), and redundant penile skin with or without lymphedema occurred in
      18 (30%). The complications occurred in 18 of 25 patients (72%) in group 1 (A
      through C) but in only 8 of 35 (23%) in group 2. The difference was significant
      (P =.001). Most of the complications were mild and acceptable. A second procedure
      was required in 5 of the 25 patients in group 1 but in none of group 2. The
      second procedures were required to correct recurrent buried penis in 1 and to
      resect excess redundant penile skin in 4. CONCLUSION: The superior results
      achieved in group 2 suggest that in addition to penoplasty with adequate fixation
      of the unfurling prepuce, resection of excess inner preputial skin is required to
      achieve an optimal outcome in children requiring surgical correction of buried
      penis.

PMID- 11226989
TI  - Pulsed Doppler sonography for the diagnosis of strangulation in small bowel
      obstruction.
AB  - BACKGROUND/PURPOSE: This study was undertaken to assess the usefulness of pulsed
      Doppler sonography (PDS) for the detection of strangulation in small bowel
      obstruction by evaluating the hemodynamics in the superior mesenteric artery
      (SMA). METHODS: The authors performed PDS in 117 normal children: 22 children
      aged 0 to 1 months (group I), 27 children aged 1 to 12 months (group II), 36
      children aged 1 to 6 years (group III), and 32 children aged 7 to 15 years (group
      IV). Patients included 25 with simple obstruction: 1 in group II, 10 in group
      III, and 14 in group IV; and 9 with strangulating obstruction: 2 in group I, 2 in
      group II, 3 in group III, and 2 in group IV. The authors measured the peak
      systolic velocity, end-diastolic velocity (EDV), and mean average velocity and
      calculated the resistive index (RI). RESULTS: The authors observed both a
      significant decrease in the EDV and increase in the RI for the SMA in
      strangulating obstruction compared with simple obstruction. CONCLUSION: Analysis
      of the hemodynamics in the SMA using PDS is useful to differentiate strangulating
      obstruction from simple obstruction.

PMID- 11226990
TI  - Liver transplantation for biliary atresia associated with malignant hepatic
      tumors.
AB  - The authors report 3 cases of liver transplantations in children between 4 and 10
      years of age, complicated with malignant hepatic tumors after biliary atresia.
      The preoperative abdominal computed tomography (CT) scans of all 3 cases showed
      hepatic masses. The serum alpha-fetoprotein levels were elevated highly in 2
      cases. After living-related liver transplantation (LRLT), the pathologic findings
      of the masses in the resected livers showed hepatocellular carcinoma in 2 cases
      and hepatoblastoma in the other. All cases were associated with biliary
      cirrhosis. The stage of the liver tumor in the 3 cases using the TNM system was
      IVA (T4, N0, M0), II (T2, N0, M0) and IVA (T4, N0, M0). Chemotherapy was used in
      all cases after liver transplantation, and all patients survived with no
      recurrence. The results suggest that even though malignant liver tumors rarely
      are complicated with biliary atresia in childhood, one should be alert to the
      occurrence of hepatic malignancy and perform routine screening of alpha
      fetoprotein levels, abdominal CT scans, and magnetic resonance imagings.

PMID- 11226991
TI  - Drugs, guns, and kids: the association between substance use and injury caused by
      interpersonal violence.
AB  - BACKGROUND: Drug and alcohol uses have been linked to the frequency of injury
      events, recurrent hospital admission for injury, and interpersonal violence. Data
      regarding the association of recent substance use and injury type and frequency
      in children and young adults are not available. Such data probably would be
      valuable in planning interventions to prevent substance use and reduce the risks
      of injuries. METHODS: Evidence of substance use was assessed in trauma patients
      presenting to the authors' level 1 trauma center over a 6-month interval.
      Demographic data, mechanisms of injury, revised trauma scores (RTS), injury
      severity scores (ISS), hospital days, and mortality rate were evaluated. Chi
      square analysis and 2-tailed, paired t tests were used for statistical analysis.
      Multivariate logistic regression was utilized to determine the influence of
      individual variables. RESULTS: From a total group of 743 patients with life
      threatening injuries, trauma registry records of 186 patients less than 21 years
      old were eligible for evaluation, and 126 of these had complete blood and urine
      drug assessments completed on admission to the trauma center. Forty-two percent
      (53 of 126) patients tested positive for alcohol or drugs. No patients less than
      14 years of age (n = 61) had positive drug screen results. However, in the cohort
      of patients aged 14 and 15 (n = 17), 71% tested positive. Also, 72% of
      adolescents (age < 18) who were victims of injuries from gunshot wounds had
      evidence of substance use. Multivariate analysis showed gunshot wounds (P <.003)
      to be associated independently with positive drug screens. No statistical
      differences were observed in ethnic distribution, ISS, RTS, hospital days, or
      mortality rate when patients with positive screen results were compared with
      those without evidence of substance use. CONCLUSIONS: Trauma victims had evidence
      of substance use in early teen age years especially in the 14 and 15-year-old age
      groups. Toxicology screening disclosed that substance use is associated strongly
      with gunshot wounds. Substance use, along with poverty, inadequate family
      support, and peer pressure are factors that influence injury risk. Interventions
      to prevent substance use in young children may reduce the risk of injury.

PMID- 11226992
TI  - Serum hyaluronic acid as an early prognostic marker in biliary atresia.
AB  - PURPOSE: The aim of this study was to assess whether serum concentrations of
      hyaluronic acid (HA), measured at diagnosis is an early biochemical marker of
      prognosis in biliary atresia. METHODS: Serum HA was measured at diagnosis using a
      radiometric assay in 84 infants with biliary atresia (BA), and related to outcome
      by 5 years of age. RESULTS: Serum HA was higher in the 29 patients who died or
      required liver transplant by 5 years of age compared with the 56 who survived to
      5 years without transplant (490 +/- 216 microg/L v 262 +/- 163 microg/L; P <.001,
      95% confidence intervals of the difference 145 to 311 microg/L). CONCLUSION: High
      serum concentrations of HA at diagnosis may help to identify at an early stage
      those patients with BA who have a poor prognosis and will require liver
      transplant by 5 years of age.

PMID- 11226993
TI  - Pheochromocytoma in children.
AB  - BACKGROUND/PURPOSE: Etiopathogenesis, management, and outcome of pediatric
      pheochromocytoma (PHEO) still is obscure because of limited number of cases.
      Therefore, a retrospective clinical study was performed to present an updated
      picture of the entire spectrum of pediatric PHEO based on the authors' 30 years'
      experience consisting of one of the largest noncollected series treated in a
      single medical center. METHODS: Records of patients treated for PHEO in the
      authors' unit from 1970 to 1999, inclusive, were reviewed retrospectively.
      Information recorded for each patient included age, sex, past medical and family
      history, clinical characteristics, diagnostic methods, treatment, pathologic
      findings, and outcome. RESULTS: Sixteen children with a mean age of 10.7 +/- 2.9
      years consisting of 12 boys and 4 girls were treated for PHEO. Most of the tumors
      were right sided (n = 6) and bilateral (n = 6). Sporadic cases of PHEO accounted
      for 14 patients (88%), whereas 2 children had von Hippel-Lindau (VHL) disease and
      multiple endocrine neoplasia type 2b (MEN2b). Hypertension was the most common
      symptom followed by headache and sweating. The diagnosis of PHEO was made by
      laboratory and radiologic studies. Preoperative medical therapy was done in all
      patients. Laparotomy confirmed that 11 patients had localized, 4 patients had
      regional, and 1 patient had metastatic disease. The localized tumors were excised
      totally by bilateral (n = 4) and unilateral (n = 6) adrenalectomy. Surgical
      procedures performed for regional disease were total excision (n = 2), incisional
      biopsy (n = 1) and partial excision (n = 1). Incisional biopsy could be taken
      only from a patient with metastatic disease at presentation. Two patients with
      localized disease and 2 patients with regional disease had benign recurrences in
      right (n = 2) and left (n = 2) adrenal glands within 3 to 7 years after
      operation. Total excision of the recurrent tumors was done in all patients.
      Pathologic examination found apparently malignant features in 3 patients who
      presented with regional (n = 2) or metastatic (n = 1) disease and underwent
      incisional biopsy (n = 2) or partial excision (n = 1). Pathologic features
      suggestive of malignancy were noted in 4 patients presenting with regional (n =
      2) and localized disease (n = 2). Apparently benign pathologic features were
      noted in the remaining 9 patients. There was not any operative mortality in our
      series. Adjuvant chemotherapy was commenced postoperatively in all patients with
      malignant and suggestive of malignant pathologic features. During the long-term
      follow-up for 16 years, 3 patients died (19%). One patient with VHL disease died
      of astrositoma 5 years after her recurrent PHEO was excised. Of the 3 patients
      with malignant disease, 2 patients in whom only incisional biopsies were done had
      distant metastases and died of disease within 2 years. Another patient with
      malignancy who had MEN2b was lost to follow-up. CONCLUSIONS: Early diagnosis and
      total excision are the most important aspects of accurate treatment for childhood
      PHEO. Pre- intra- and postoperative medical management is as important as the
      surgical procedure. Our surgical treatment policy is mainly minimizing the risk
      of recurrence while preserving adequately functioning adrenal medullar tissue.
      Incomplete excision and advanced-stage disease are the major determinants of poor
      outcome. None of the clinical, laboratory, or pathologic features are reliable
      predictors for recurrence and discrimination of malignancy. Because of the
      steadily increasing incidence of precancerous genetic syndromes related to
      adrenal glands and poor prognosis of advanced-stage PHEO, childhood cases of
      hypertensive disorders should receive a detailed and vigorous diagnostic
      evaluation and appropriate treatment as given to adults.

PMID- 11226994
TI  - The effect of rectosigmoidectomy and Duhamel-type pull-through procedure on lower
      urinary tract function in children with Hirschsprung's disease.
AB  - BACKGROUND/PURPOSE: The aim of this study was to investigate the effect of
      rectosigmoidectomy and Duhamel-type pull-through procedure on lower urinary tract
      function in children with Hirschsprungs disease. METHODS: During a 3-year period
      the authors assessed 11 consecutive children with Hirschsprung's disease
      prospectively by standard urodynamic investigations, before and after surgery.
      Urodynamics included simultaneous measurement of abdominal pressure, bladder
      pressure, detrusor pressure, and pelvic floor electromyography during filling and
      voiding. All children were submitted to laparoscopic resection of the aganglionic
      bowel segment below the cul de sac and a Duhamel-type pull-through procedure.
      Postoperatively, the children were assessed urodynamically and evaluated every 3
      months for urologic problems. RESULTS: Mean age at first urodynamic study was 5
      months (range, 2 to 10). Postoperative urodynamics were performed at a mean age
      of 10 months (range, 5 to 159). The mean interval between operation and
      postoperative urodynamic study was 6 months (range, 2 to 10). No child had
      structural urologic anomalies or urologic problems before surgery, and all had
      normal preoperative urodynamic findings. After surgery, urodynamics were
      considered normal in 3 children. In 7 children cystometric bladder capacity (CBC)
      was abnormally large, and 6 of these children had significant residuals. However,
      all had detrusor contractility and were able to void spontaneously. One child had
      low bladder compliance postoperatively. Despite the urodynamic changes, no child
      had clinical urologic problems at further follow-up. Mean follow-up after surgery
      was 24 months. CONCLUSIONS: This study found that after rectosigmoidectomy below
      the cul de sac alterations of bladder function can be observed. In 7 of the 11
      patients studied, mean cystometric bladder capacity was 87% higher than capacity
      estimated for age. Moreover, postoperative residuals were 156% higher than the
      preoperative values. These findings suggest that partial detrusor denervation is
      likely in these patients. However, because detrusor contractility was present,
      and none of the children had retention or any urologic problems, the findings
      must be interpreted carefully. Because children with Hirschsprung's disease
      generally do not have preexisting urologic problems, routine preoperative
      urodynamic screening is not necessary. However, children with voiding problems
      after operation should be investigated urodynamically. For legal reasons parents
      should be informed of possible urologic problems, especially if subtotal
      resection of the aganglionic bowel segment is planned.

PMID- 11226995
TI  - Benefits of oral administration of an electrolyte solution interrupting a
      prolonged preoperatory fasting period in pediatric patients.
AB  - PURPOSE: The aim of this study was to evaluate the benefits of an oral isosmolar
      solution of electrolytes (ISE) administered to interrupt a prolonged fasting
      period in children undergoing an elective surgical procedure under general
      anesthesia. METHODS: Forty unpremedicated children aged 3 to 12 years, ASA I,
      undergoing a surgical procedure requiring general anesthesia were assigned
      randomly to 1 of 2 groups. Group 1 consisted of patients with an overnight
      fasting period for milk and solids of at least 8 hours. In group 2, patients
      under a similar fasting period received a volume of 4 mL/kg of an oral ISE 3
      hours before completing the fasting period. After anesthetic induction, blood
      glucose level (BGL) was quantified, and patients underwent an endoscopic
      examination to obtain the gastric content to determine the residual gastric
      volume (RGV) and pH levels. RESULTS: In group 1, the RGV was 0.78 +/- 0.44 mL/kg,
      pH was 1.75 +/- 0.38, and BGL was 86.4 +/- 14.5. In group 2, the RGV was 0.40 +/-
      0.29 mL/kg, pH was 3.18 +/- 0.61, and BGL was 85.1 +/- 12.6. Only RGV and pH were
      significantly different between groups. CONCLUSION: A prolonged fasting period
      interrupted with oral ISE administration resulted in an RGV of low risk, without
      counterbalancing a potential fasting-induced hypoglycemia.

PMID- 11226996
TI  - Comparison of granisetron, droperidol, and metoclopramide for prevention of
      postoperative vomiting in children with a history of motion sickness undergoing
      tonsillectomy.
AB  - BACKGROUND/PURPOSE: A history of motion sickness is one of the patient-related
      factors associated with postoperative vomiting (POV). This study was undertaken
      to compare the efficacy of granisetron, droperidol, and metoclopramide for the
      prevention of POV after tonsillectomy in children with a history of motion
      sickness. METHODS: In a prospective, randomized, double-blinded trial, 90
      pediatric patients, aged 4 to 10 years, received granisetron, 40 microg/kg;
      droperidol, 50 microg/kg; or metoclopramide, 0.25 mg/kg (n = 30 of each)
      intravenously after an inhalation induction of anesthesia. Emetic episodes and
      safety assessments were performed during the first 24 hours after anesthesia.
      RESULTS: Twenty-two of 30 patients (73%) who had received granisetron were emesis
      free during the first 24 hours after surgery as compared with 7 of 30 (23%) who
      had received droperidol (P <.05) or 6 of 30 (20%) who had received metoclopramide
      (P <.05). No clinically serious adverse events were observed in any of the
      groups. CONCLUSION: Prophylactic therapy with granisetron is superior to
      droperidol or metoclopramide for the prevention of POV after tonsillectomy in
      children with a history of motion sickness.

PMID- 11226997
TI  - Diagnostic laparoscopy in prolonged jaundice.
AB  - BACKGROUND: The early diagnosis of surgical jaundice in a neonate is an important
      step for the surgical success in extrahepatic biliary atresia. Diagnostic
      laparoscopy, as in many areas in surgery, is included in the conventional
      diagnostic methods of extrahepatic biliary atresia. METHODS: Since 1992, 24
      infants with prolonged jaundice, in whom extrahepatic biliary atresia and
      neonatal hepatitis could not be differentiated with conventional diagnostic
      interventions, have been evaluated laparoscopically. RESULTS: A coarse,
      irregular, greenish-brown liver with some degree of fine angiomatous development
      and an atretic gallbladder are the findings of laparoscopic evaluation in an
      infant with extrahepatic biliary atresia. However, in neonatal hepatitis, the
      liver is smooth, sharp-edged, and chocolate brown in color, and simultaneously
      performed cholangiography should show the passage of the contrast material both
      into the proximal biliary tracts and the intestinal system. In this series, 10 of
      24 cases were proved to be neonatal hepatitis diagnosed by laparoscopy, so
      unnecessary laparotomy was avoided in 42% of the cases. CONCLUSION: When the
      diagnostic laparoscopy, in which the liver and the gallbladder are directly
      visualized, is combined with the cholangiographic examination, the most accurate
      and earlier diagnosis in an infant with prolonged jaundice can be achieved, and
      the important period of time for the surgical success in extrahepatic biliary
      atresia will be minimally wasted.

PMID- 11226998
TI  - Ultrasound assessment of scald scars in Asian children receiving pressure garment
      therapy.
AB  - BACKGROUND/PURPOSE: Scar formation after scald injury in children is managed
      commonly by application of pressure garment. The duration of the treatment
      depends on clinical assessment. The objective of the study was to evaluate the
      efficacy of the pressure garment therapy and to correlate the clinical assessment
      scar thickness with ultrasound measurement. METHODS: Prospective study of
      children with hypertrophic scars receiving pressure garment therapy was carried
      out between 1993 and 1998. The scars were mapped with paper cutting.
      Representative scar sites were scored clinically according to Vancouver General
      Hospital Burn Assessment Scale (pigmentation, vascularity, pliability, height,
      pain, itchiness). Blind to the clinical results, 2 radiologists measured the scar
      thickness of the same sites with ultrasonography (5 to 10 MHz transducer, General
      Electric LOGIQ 500). The correlation between the clinical scores and ultrasound
      measurement of scar thickness were analysed using analysis of variance (ANOVA).
      RESULTS: The median age of 58 children with scald injury (M:F = 36:22) was 2.8
      years (0.5 to 15.8 years). The mean percentage of scald was 8.8% (24% had scald
      area >10%). In addition, there were 5 children with burn from naked flame and 9
      children with keloid secondary to surgical incisions. With pressure garment
      therapy, the scar thickness reached a plateau 1 (1/2) years after the injury and
      began to decline gradually thereafter. The clinical estimation of scar thickness
      correlated well with the ultrasound measurement (ANOVA, P =.003, Adjusted R
      square = 0.99). The accuracy rate of clinical thickness estimation was 67%.
      Overestimation and underestimation accounted for 15% and 18%, respectively. There
      also was good correlation between total clinical score and the ultrasound
      measurement (ANOVA, P <.001). CONCLUSIONS: In children with scald injury, the
      pressure garment needs to be continued for a minimum of 1 year. Ultrasound
      measurement correlates well with overall score of the Vancouver General Hospital
      Burn Assessment Scale but not individual components of the scoring system except
      wound height.

PMID- 11226999
TI  - Surgery for lung abscess in immunocompetent and immunocompromised children.
AB  - PURPOSE: The aim of this study was to evaluate the surgical management results of
      lung abscess in immunocompetent and immunocompromised children. METHODS: Surgery
      was performed on 30 children with lung abscess or necrotizing pneumonia
      refractory to medical treatment in a 12-year period. Of them, 23 were
      immunocompetent, and 7 were immunocompromised. Pulmonary resection was performed
      including unilateral lung in 28, bilateral in 2, and 2 lobes in 6. Concomitant
      decortication was performed in 18 (78.2%) immunocompetent patients. RESULTS:
      Increased incidence of surgery for lung abscess was caused mainly by drug
      resistant and fungal infection. Surgery was performed commonly for bacterial lung
      abscess on patients less than 5 years old and fungal lung abscess on adolescence.
      A multiple small abscess was the predominant type of abscess in immunocompetent
      patients, whereas 2-lobe involvement tended to occur in immunocompromised
      patients. Fungal lung abscess tended to occur on left lung and in female
      patients. Left lower lobe was involved most commonly in both groups of patients
      in which majority need lobectomy. Immunocompromised patients required a more
      extensive pulmonary resection. There were 3 postoperative complications
      (morbidity of 10.2%) with no postoperative mortality. Length of postoperative
      hospital stay ranged from 6 to 85 days with average of 18.4 days. CONCLUSIONS:
      The incidence and pattern of lung abscess that required surgery between
      immunocompetent and immunocompromised children were different. A more aggressive,
      extensive surgical procedure is preferable for immunocompromised patients, and
      the surgical results were comparatively excellent to immunocompetent patients.
      However, the prognosis of immunocompromised children depends on their underlying
      disease process.

PMID- 11227000
TI  - Two-dimensional alterations of myenteric plexus in jejunoileal atresia.
AB  - PURPOSE: The purpose of this report is to investigate changes in the myenteric
      plexus associated with the dilated proximal segment of jejunoileal atresia (JA).
      Two-dimensional morphologic changes in the myenteric nerve plexuses were
      investigated using whole-mount preparation. METHODS: Proximal (P) and distal (D)
      intestinal segments from 7 cases with JA and control (C) segments from 5
      postmortem neonates were investigated. The circumference of the jejunoileal
      segments was measured after fixation. Antibodies for protein gene product 9.5 and
      neurofilament protein were used in whole-mount preparation. The sizes of neural
      networks were calculated by measuring the longest circular distance in a neural
      network (x) and the longest longitudinal distance (y), and the width of the
      internodal strands (i) with a videomicrometer. RESULTS: Median circumference of
      the segments was 8.5 in P, 2.0 in D, and 2.0 cm in C. The neural networks in P
      were expanded longitudinally as well as circularly (x = 817.10 microm, y =
      561.26, i = 31.04: median) while comparing them to those in D (x = 431.40 microm
      y = 288.07, i = 26.05) or C (x = 285.03 microm y = 372.20, c = 1113.57, i =
      32.39). The nerve plexus was less expanded than the intestinal wall. CONCLUSIONS:
      Proximal intestinal segments showed a restructuring that resulted in mild
      hypoplasia of the enteric nerve plexuses in the proximal segments. The less
      expansion of the myenteric nerve plexus seen in the proximal bowel in infants
      with JA suggests a histologic basis for the efficacy of tapering or plication of
      the dilated bowel.

PMID- 11227001
TI  - Air enema for diagnosis and reduction of intussusception in children: clinical
      experience and fluoroscopy time correlation.
AB  - PURPOSE: The objective of this study was to correlate the fluoroscopy time with
      radiologic outcome in the pneumoreduction of intussusception in children.
      METHODS: From September 1995 to December 1997, a prospective analysis of 181
      cases of pediatric intussusception with pneumoreduction without sedation was
      done. A receiver operating characteristic curve of fluoroscopy time was drawn for
      correlation with radiologic outcome. RESULTS: The overall success and failure
      rates of pneumoreduction were 84% and 16%, respectively. Three patients (1.6%)
      experienced colon perforation. The mean fluoroscopy time was 2.8 +/- 1.7 minutes
      in successful procedure and 4.9 +/- 2.8 minutes in failed procedures (P < 0.001).
      Analysis of the receiver operating characteristic curve of fluoroscopy time
      indicates that 4 minutes fluoroscopy time was a good critical point in
      differentiating successful and failed cases. In those 18 patients who had
      successful reduction with fluoroscopy times of more than 4 minutes, 4 patients
      had clinical symptoms for more than 1 day and 14 patients less than 1 day. One of
      those 4 patients required operation 1 day later because of peritonitis caused by
      necrosis of terminal ileum. Two patients had high fever in the next 2 days and
      recovered after antibiotic treatment. CONCLUSIONS: Pneumoreduction is a good
      method in treatment of intussusception with high successful rate. Four minutes is
      the critical point of procedure. Reduction with greater than 4 minutes in those
      patients having illness more than 1 day might not benefit and have more
      complications.

PMID- 11227002
TI  - Prognostic factors of mortality in newborns with necrotizing enterocolitis
      submitted to exploratory laparotomy.
AB  - PURPOSE: The aim of this study was to identify and assess mortality predictive
      factors in newborns with necrotizing enterocolitis (NEC) requiring emergency
      exploratory laparotomy. METHODS: A prospective study of 91 newborns with NEC
      submitted to exploratory laparotomy was conducted. Clinical outcomes were death
      and survival 60 days after surgery. Nine variables were analyzed: weight at
      birth, gestational age, intrauterine growth, sex, gas in the portal vein at
      abdominal x-ray, pneumoperitoneum, extent of the disease, operative strategies,
      and extension of bowel resection. Univariate and multivariate analyses were
      performed to identify mortality predictors. RESULTS: Mean weight at birth was
      1,676 +/- 634.8 g, and mean gestational age was 34 +/- 2.8 weeks. Thirty-nine
      newborns (42.9%) presented intrauterine growth retardation. Operative techniques
      included bowel resection with enterostomy (80 patients), bowel resection with
      primary anastomosis (10 patients), and decompressive enterostomy (1 patient). Six
      deaths occurred caused by co-existing disease. NEC-related mortality rate was
      46.15% (42 of 91). CONCLUSIONS: Two variables, intrauterine growth retardation,
      and diffuse bowel involvement, were predictive of mortality according to both
      univariate and multivariate analyses. Site of bowel involvement seems to be
      important mortality predictors in infants with NEC requiring surgery. The size of
      our population did not allow statistical analysis of this relationship. Further
      studies should focus on examining this aspect.

PMID- 11227003
TI  - Predictors of acquiring a nosocomial bloodstream infection on extracorporeal
      membrane oxygenation.
AB  - PURPOSE: The aim of this study was to identify independent predictors of
      acquiring a nosocomial bloodstream infection (BSI) during extracorporeal membrane
      oxygenation (ECMO). METHODS: This retrospective cohort consisted of 202 neonates
      treated with ECMO from 1989 to 1998 at the author' institution. Data collected
      included patient demographics, primary and secondary diagnoses, white blood cell
      counts, antibiotic usage, presence of central lines, operative procedures, and
      outcome. Surveillance blood cultures were drawn daily from the circuit using
      sterile technique to identify acquired pathogens. Statistical analyses included
      logistic regression, Cox proportional regression analysis, and discriminate
      analysis. RESULTS: There were 1,245 blood cultures drawn on 202 patients (6.2
      cultures per patient), and a nosocomial BSI was identified in 7 patients (3.4%)
      during this 10-year span. These were infections that were neither present nor
      incubating on admission. Pre-ECMO diagnoses of patients who had a nosocomial BSI
      while on bypass included group B beta-hemolytic streptococcal sepsis (n = 2),
      herpes simplex viral sepsis (n = 1), congenital diaphragmatic hernia (n = 2),
      persistent pulmonary hypertension (n = 1), and congenital heart disease (n = 1).
      The median time on ECMO before obtaining a positive culture was 390 hours. The
      infectious agents responsible for these BSIs included Staphylococcus epidermidis
      (n = 5), Staphylococcus aureus (n = 1), and Escherichia coli (n = 1). The major
      factor associated with acquiring a nosocomial BSI on ECMO was the duration of
      bypass (391 v 141 hours, P =.002). Additionally, patients in the BSI group were
      more likely to have had an arterial catheter in place (16 v 7 days, P =.009) and
      to have received more screening blood cultures (16 v 6 cultures, P < 001). White
      blood cell counts, absolute neutrophil counts, and immature/total (I/T) ratios
      were not useful in predicting a nosocomial BSI. Of the 31 patients who required
      ECMO for more than 10 days, 7 (23%) had a positive blood culture, and 5 of these
      7 infants (71%) died (P =.03). CONCLUSIONS: The only predictor of acquiring a
      nosocomial BSI on ECMO was the duration of support for greater than 10 days.
      Because classical predictors of infection are unreliable while the patient is on
      ECMO, the authors suggest that obtaining daily surveillance blood cultures
      beginning on the tenth day should be performed with prolonged ECMO courses. The
      authors confirmed previous reports of the association between a prolonged ECMO
      course and a high mortality rate. However, the authors speculate that, in
      actuality, the primary diagnosis leads to the prolonged course of support and is
      the major factor in the infant' demise.

PMID- 11227004
TI  - Hypercalcemia associated with extracorporeal life support in neonates.
AB  - BACKGROUND/PURPOSE: Disturbances in calcium homeostasis are common at initiation
      of extracorporeal life support (ECLS). At the authors' institution many neonates
      undergoing ECLS have developed hypercalcemia. To determine the frequency of
      hypercalcemia in neonates during ECLS we performed retrospective chart review of
      neonates that required ECLS at our neonatal intensive care unit. METHODS: The
      authors identified 76 consecutive neonates who underwent ECLS before 10 days of
      age at Cincinnati Children's Hospital Medical Center from July 1, 1991 to June
      30, 1996. The hospital charts and ELSO forms were reviewed. Demographic,
      clinical, and laboratory data for each of the patients were reviewed, both before
      initiation and during ECLS. Hypercalcemia was defined as total serum calcium
      concentration of greater than 11 mg/dL (2.74 mmol/L) on at least one occasion
      beyond the first 24 hours of ECLS. RESULTS: The hospital charts and ELSO forms
      from 70 patients were available for review. One patient was excluded because he
      was only on ECLS for 33 hours, and there were no calcium levels obtained after 24
      hours of ECLS and until death. Twenty-five (36%) neonates undergoing ECLS had
      hypercalcemia (serum Ca > 11 mg/dL [2.74 mmol/L]). Hypercalcemia was associated
      with longer duration of ECLS (hypercalcemia group, 243 +/- 115 hours and
      normocalcemia group, 139 +/- 64 hours) and greater requirements for platelet
      transfusions (hypercalcemia group, 538 +/- 282 mL and normocalcemia group, 372 +/
      233 mL). This could not be explained by differences in primary diagnosis,
      amounts of calcium administered, and acid-base status. CONCLUSIONS: Hypercalcemia
      was found to be common in neonates that require ECLS and is associated with
      longer duration of ECLS support. Conservative calcium administration for neonates
      while on ECLS may be warranted.

PMID- 11227005
TI  - Acute lower gastrointestinal bleeding as a late complication of spinal
      instrumentation.
AB  - Posterior or anterior fusion with spinal instrumentation is a well-known
      operation for scoliosis. There are multiple potential complications; the most
      common are blood loss during the initial surgery and wound infection. Vascular
      injury has been reported. However, to the authors' knowledge, acute
      gastrointestinal bleeding has not been reported. The authors report on a child
      who presented 6 years after posterior spinal instrumentation with massive acute
      lower gastrointestinal bleeding resulting from internal iliac artery injury and
      bowel perforation. The etiology, diagnosis, and management of such bleeding is
      reviewed.

PMID- 11227006
TI  - Antenatal detection of a pancreatic foregut duplication cyst.
AB  - Congenital pancreatic cyst is a rare cause of a cystic abdominal mass in the
      neonate. The authors report a case of antenatal detection of a foregut
      duplication cyst arising entirely from the pancreas.

PMID- 11227007
TI  - Endoscopic drainage for pancreatic pseudocyst in children.
AB  - The authors report here the results of endoscopic cystogastrostomy performed on 3
      children aged 11, 3, and 2.5 years with nonresolving pancreatic pseudocyst (PP)
      of 12, 9.5, and 7 cm in diameter. The etiology of PP was abdominal trauma in 2
      and idiopathic acute pancreatitis in 1 case. Ultrasound and computed tomography
      scans confirmed the diagnosis and suitability for gastric drainage. After the
      puncture of cyst, a double pig-tail stent was placed for the permanent drainage
      of cystogastrostomy. Complete regression was confirmed by follow-up
      ultrasonography at 8, 6, and 7 weeks, respectively. There were no procedure
      related complications, nor was there a recurrence of cyst during the 2 years of
      follow-up. This report suggests that children with nonresolving PP, that are
      anatomically accessible, can be treated successfully and safely by endoscopic
      drainage.

PMID- 11227008
TI  - A case of biliary atresia with duplication of the common bile duct.
AB  - The authors report a case of biliary atresia (BA) with duplication of the common
      bile duct. A 1-month-old girl was referred for investigation of persistent
      jaundice. BA was suspected and confirmed with intraoperative cholangiography. A
      portoenterostomy was performed at 50 days of age. During dissection of the
      fibrous remnant of the common bile duct, a separate fibrous bile duct remnant
      running in parallel on the left, was identified. Histologically, there was bile
      duct proliferation at the porta hepatis of the left bile duct remnant. A
      diagnosis of BA with duplicated common bile duct was made. Postoperative course
      was uneventful, and at a follow-up assessment at 7 months, she was jaundice free,
      and her progress has been unremarkable.

PMID- 11227009
TI  - Intestinal obstruction caused by an ectopic fallopian tube in a child: case
      report and literature review.
AB  - The authors present the case of a prepubertal 14-year-old girl who was admitted
      for an acute abdominal pain, fever, and vomiting. She was in a poor general
      state, having recently suffered a weight loss of 5 kg. A plain abdominal x-ray
      disclosed signs of mechanical ileus. An abdominal ultrasound scan showed a normal
      uterus, a normal right-sided ovary, but no left ovary. An emergency laparoscopy
      found a normal uterus with complete absence of the left ovary and salpinx, the
      upper left dome of the uterus being smooth with no visible horn. The right ovary
      and salpinx were normal. Intestinal obstruction was caused by a strangulating
      cordlike structure of unclear origin. After converting to a laparotomy, we found
      an abnormal fallopian tube inserted in the left parieto-colic groove. The tube
      extended next on the lateral sigmoid mesentery and wrapped itself around the
      ileum, provoking a local strangulation and an ischemic covered bowel perforation.
      The bowel perforation was treated by a segmental bowel resection. Careful
      dissection of the cordlike structure disclosed a true rudimentary fallopian tube
      with hypotrophic fimbriae and a small distal round structure containing ovarian
      tissue. These structures were removed entirely. A review of the literature on
      this rare situation is presented and discussed.

PMID- 11227010
TI  - Ovarian adenocarcinoma in premenarchal girls.
AB  - Ovarian neoplasms are unusual in the paediatric age group; the majority of them
      are of germ cell origin. Malignant epithelial tumours of the ovary occur
      infrequently in adolescent girls. Ovarian carcinoma in particular is extremely
      rare before puberty. The authors describe 3 cases of adenocarcinoma of the ovary
      in premenarchal girls and highlight the unique characteristics of this tumour in
      this age group.

PMID- 11227011
TI  - Catheter knotting in a catheterizable urinary reservoir.
AB  - An 11-year-old boy with bladder extrophy was treated ultimately with an
      ileocystoplasty and a catheterizable stoma. In attempting to drain his bladder
      via intermittent catheterization, the catheter became lodged. This case details
      the surgical treatment of a knotted catheter in an urinary reservoir.

PMID- 11227012
TI  - Hemangiomatosis presenting as meralgia paresthetica.
AB  - The authors present a 15-year-boy with meralgia paresthetica caused by the
      recurrence of a diffuse congenital hemangiomatosis in the pelvic region. Relief
      of the patient's symptoms was achieved by neurolysis of the lateral femoral
      cutaneous nerve in the thigh and partial excision of the tumor. To our knowledge,
      hemangiomatosis has never been suggested as a cause of meralgia paresthetica.

PMID- 11227013
TI  - Tracheobronchial injuries in childhood: review of two cases.
AB  - Penetrating injuries of the tracheobronchial tree in children are very rare. With
      prompt diagnosis nonoperative treatment seems to be appropriate and safe without
      complications. Delayed diagnosis may result in surgical exploration with severe
      complications afterwards caused by poor condition at the time of intervention.
      Two children with penetrating tracheobronchial injuries were referred to our
      pediatric surgical center in the last 12 years. A 10-year-old boy suffered an
      iatrogenic penetrating injury of the tracheobronchial tree, and a 6-year-old boy
      a direct penetrating injury of the distal trachea in an agricultural accident.
      Cervical emphysema and bronchoscopy identified the lesion in these patients. Both
      of them could be treated conservatively without any sequelae.

PMID- 11227014
TI  - Floating nonocclusive thrombus in the common femoral artery detected by duplex
      scanning after removal of the arterial catheter: a case report.
AB  - A 5-year-old girl is reported in whom duplex scanning showed a nonocclusive
      thrombus in the common femoral artery that was removed successfully by surgical
      intervention. Noninvasive examination with duplex scanning in patients with signs
      of acute arterial insufficiency during or after removal of femoral artery
      catheter is recommended.

PMID- 11227015
TI  - Inferior vena cavectomy for nonexcisable Wilms' tumor thrombus.
AB  - Wilms' tumor with tumor extension into the vena cava is a not uncommon variant of
      tumor presentation. Typically, this extension is nonadherent to the endothelium
      and readily lends itself to removal either before or after chemotherapy. This
      case illustrates an unusual variant in which the tumor within the cava was
      tightly adherent to the venous wall and required the complete excision of the
      vena cava, left renal vein, and a portion of the iliac system.

PMID- 11227016
TI  - Colon atresia--type III.

PMID- 11227017
TI  - Management of parapneumonic collections in infants and children.

PMID- 11227019
TI  - Identification of effective constituents of influenza vaccine by immunization
      with plasmid DNAs encoding viral proteins.
AB  - The use of plasmid DNA encoding influenza viral proteins to vaccinate animals
      constitutes a promising approach to the development of effective subunit
      vaccines. This review describes the results obtained by the immunization of mice
      with such plasmid DNAs. (i) Both hemagglutinin (HA)- and neuraminidase (NA)
      expressing DNAs for the surface glycoproteins from A/PR/8/34 (H1N1) or
      B/Ibaraki/2/85 virus can provide the most effective protection against influenza
      A-type or B-type virus infection among the various viral protein-expressing DNAs
      tested in BALB/c mice. (ii) A mixture of plasmid DNAs encoding HA and NA can
      provide more effective protection against virus challenge than plasmid DNA
      encoding HA or NA alone in BALB/c mice. (iii) NA-DNA can provide protection
      against infection not only by homologous virus but also by drift viruses. (iv) HA
      DNA from A/PR/8/34 (H1N1) virus provides significant protection only in BALB/c (H
      2(b)) mice, whereas HA-DNA from B/Ibaraki/2/85 virus affords significant
      protection in BALB/c, B10 (H-2(d)), and C3H (H-2(k)) mice. NA-DNA from both A
      type and B-type viruses provides significant protection in the three strains of
      mice. These results suggest that both HA and NA molecules should be used as
      vaccine components to provide effective protection against influenza A-type and B
      type virus infection in genetically heterogeneous humans.

PMID- 11227020
TI  - Current problems of amebiasis in Japan and recent advances in amebiasis research.
AB  - Amebiasis is epidemic in two major populations in Japan: male homosexuals and
      institutionalized people. Currently available diagnostic, chemotherapeutic, and
      prophylactic measures and their problems are discussed. Recent advances in basic
      research on amebiasis are also described with new findings of unique metabolisms
      and intracellular structures and organization. Discoveries and analyses of the
      unique features presented by this parasitic protist help in our elucidation of
      the pathogenic mechanisms of the parasite and may eventually lead to the
      development of new drugs and vaccines against amebiasis.

PMID- 11227021
TI  - High prevalence of antibody to Toxoplasma gondii among humans in Surabaya,
      Indonesia.
AB  - Infection with Toxoplasma gondii is of medical importance in relation to a recent
      increase in cases of acquired immunodeficiency syndrome (AIDS). In the present
      study, we surveyed antibody to Toxoplasma among 1,761 people in Surabaya,
      Indonesia. The overall prevalence was 58% with significant differences between
      males (63%) and females (52%; P < 0.001). Although antibody prevalences at 0-9
      years in both genders were less than 10%, those at ages over 10 years were more
      than 50% in males or more than 40% in females, suggesting an extremely high
      transmission rate of the parasite to humans in this area. A bimodal pattern in
      the frequency distribution of Toxoplasma antibody levels suggested a persistent
      feature of Toxoplasma infection in humans.

PMID- 11227022
TI  - Molecular epidemiology of a methicillin-resistant Staphylococcus aureus
      infection.

PMID- 11227023
TI  - Leukocytopenia due to zidovudine- and nevirapine-containing regimens in elderly
      patients with HIV infection.

PMID- 11227024
TI  - Seroepidemiological survey of influenza C virus in Hiroshima Prefecture, Japan.

PMID- 11227025
TI  - Plasmid encoded enterotoxin (Pet) gene in enteroaggregative Escherichia coli
      isolated from sporadic diarrhea cases.

PMID- 11227027
TI  - Olive oil, high-oleic acid sunflower oil and CHD.

PMID- 11227028
TI  - The effect of casein phosphopeptides on calcium absorption from calcium-fortified
      milk in growing rats.
AB  - The effect of casein phosphopeptides (CPP) prepared from bovine casein by
      enzymatic hydrolysis (extrinsic CPP) on Ca absorption from Ca-fortified milk was
      studied in young male rats, in comparison with that produced from casein in the
      small intestine (intrinsic CPP). The gastrointestinal Ca disappearance (Ca
      ingested - (gastric Ca + intestinal Ca )) was calculated as an indirect
      measurement of Ca absorption. After being fasted overnight, the animals were
      given 2.0 ml Ca-fortified milk (30 g fat, 35 g protein, 2.7 g Ca/kg) without or
      with 1.0 mg extrinsic CPP/ml, by gastric intubation. The intestinal soluble Ca
      level after 15 min and the gastrointestinal Ca disappearance after 15 and 30 min
      in the rats given Ca-fortified milk with 1.0 mg extrinsic CPP/ml were
      significantly higher than these figures in the rats given Ca-fortified milk
      without CPP (P < 0.05). When the rats were given unfortified milk (1.35 g Ca/kg)
      in another reference experiment, no significant effect on intestinal soluble Ca
      and gastrointestinal Ca disappearance was apparent from the addition of CPP to
      milk. Ca availability was estimated by measuring 45Ca-deposits in the bones of
      rats 48 h after being given 2.0 ml Ca-fortified milk labelled with 45Ca (180
      kBq/2 ml) with or without 0.25 mg CPP/ml. The levels of 45Ca radioactivity of the
      femur and tibia from the rats given Ca-fortified milk with extrinsic CPP were
      significantly higher than those from the control group (P < 0.05). These results
      suggest that the addition of CPP to Ca-fortified milk could increase Ca
      absorption by growing rats mainly from CaCO3 added to the milk. The mechanism of
      CPP related to the interaction of CPP and Ca in the gastrointestinal tract is
      discussed.

PMID- 11227029
TI  - Effects of long-term parenteral administration of vitamin B6 on B6 status and
      some aspects of the glucose and protein metabolism of early-weaned piglets.
AB  - The present experiment aimed to determine the effect of feeding level and
      parenteral supplements of vitamin B6 (pyridoxine) on B6 status as well as on
      glucose, C-peptide, insulin, alpha-amino-N and urea after a gastric bolus of
      glucose in weaned piglets; the plasma tryptophan, xanthurenic acid and kynurenine
      responses to a gastric bolus of tryptophan were also measured. Forty-two piglets
      weaned at 2 weeks of age were distributed in seven blocks of six animals each.
      Within each block, the animals were assigned to the following factorial
      treatments: two levels of feeding (28 (F28) and 56 (F56) g/kg(0.75) per d)
      administered by gastric-tube feeding and three levels of parenteral
      (intramuscular injections) vitamin B6 (0 (B60), 15 (B615) and 30 (B630) mg/d). In
      B60 piglets, a decrease of 30 % and 20 % in erythrocyte and plasma pyridoxal-5
      phosphate respectively, were observed during the 2 weeks post-weaning. In
      supplemented piglets, the erythrocyte pyridoxal-5-phosphate was maximised in B615
      piglets at a level 3-4 times higher than in B60 piglets (P < 0.003). However, in
      plasma the maximal pyridoxal-5-phosphate concentration was reached in F28-B630
      piglets (P < 0.058). The glucose and insulin responses to a gastric bolus of
      glucose were lower, and the post-bolus decrease of glucose was slower, in F28
      than in F56 piglets (P < 0.0001). The insulin:C-peptide ratio was 25 % greater in
      B615 piglets (P < 0.082). After the bolus of glucose, the aminoacidaemia
      decreased differentially according to treatments (P < 0.047), while the uraemia
      was at least 2-fold higher (P < 0.001) in F28 piglets than in F56 piglets and
      tended to be maximised in B630 piglets (P < 0.074). The response of plasma
      tryptophan to the gastric bolus of tryptophan was 11 % lower in B630 piglets (P <
      0.057). The plasma concentration of kynurenine increased continuously during the
      post-bolus period and this response was more marked in F56 (P < 0.002) and in
      B630 piglets (P < 0.02). Xanthurenic acid was undetectable in any of the
      treatments. The measurements on pyridoxine status suggest that the present basal
      dietary level of B6 (7.7 mg/kg) was not sufficient to cover the metabolic needs.
      For many criteria, an optimal level was reached at 15 mg/d parenteral B6 but the
      response of urea to glucose bolus suggests that 30 mg/d was detrimental. Further
      studies are necessary to determine the dietary level of B6 equivalent to the
      present optimal parenteral supplements and its eventual effects on B6 status and
      post-weaning growth performance of piglets.

PMID- 11227030
TI  - Susceptibility of LDL to oxidative modification in healthy volunteers
      supplemented with low doses of n-3 polyunsaturated fatty acids.
AB  - The objective of the present study was to evaluate the oxidative susceptibility
      of LDL in human volunteers following supplementation with various low doses (<1
      g/d) of n-3 polyunsaturated fatty acids (PUFA). Sixty-two healthy volunteers
      (thirty-seven males and twenty-five females, aged 19-63 years) were recruited to
      take part in a randomised placebo-controlled trial. Volunteers were required to
      take 0.9, 0.6 or 0.3 g n-3 PUFA as fish oil or placebo capsules daily for 16
      weeks. Susceptibility of LDL to oxidative modification was assessed by measuring
      the production of conjugated dienes and thiobarbituric acid-reactive substances
      in LDL oxidised by Cu2+ (15 microM) or 2,2'-azobis(2-amidinopropane)
      dihydrochloride (1 mM) for 5 h. Plasma fatty acid and LDL-fatty acid composition,
      cholesterol levels and antioxidant concentrations were also measured. While post
      treatment n-3 PUFA compositions of plasma and LDL reflected the capsule contents,
      no meaningful differences in antioxidant concentrations or cholesterol levels
      were observed between the groups. Supplementation with low doses of n-3 PUFA as
      fish oil did not influence the oxidative susceptibility of LDL. The results of
      the present study suggest that moderate dietary intakes of n-3 PUFA do not
      significantly influence the susceptibility of LDL to oxidative modification in
      vitro.

PMID- 11227031
TI  - Characteristics of some wheat-based foods of the Italian diet in relation to
      their influence on postprandial glucose metabolism in patients with type 2
      diabetes.
AB  - The present study was aimed at evaluating in patients with type 2 diabetes: (1)
      the glycaemic response to four starchy foods based on wheat, typical of the
      Italian diet; (2) the importance of some food characteristics in relation to
      their effects on postprandial glucose response. Seventeen patients with type 2
      diabetes (eleven men and six women) participated in the study. All patients
      consumed, in random order and on alternate days, 50 g available carbohydrate
      provided by 90 g white bread and, according to a randomised procedure, an
      equivalent amount of carbohydrate provided by one (n 8) or two (n 9) of three
      other different test foods (g): pizza 85, potato dumplings 165, hard toasted
      bread 60. Foods had a similar nutrient composition. Plasma glucose response,
      measured for 180 min, was significantly lower after the potato dumplings than
      after white bread at 90 (P < 0.05), 120 (P < 0.01), and 150 (P < 0.05) min. No
      difference was observed in postprandial plasma insulin response after the various
      test foods. The percentage of starch hydrolysed after 5 h in vitro hydrolysis
      with alpha-amylase was about 30 % lower for potato dumplings than for the other
      foods. However, no differences in the resistant starch content, the rate of
      diffusion of simple sugars added to a dialysis tube containing the food, and the
      viscosity of digesta were observed among the test foods. Scanning electron
      microscopy of potato dumplings showed a compact structure compatible with
      impaired accessibility of starch to digestive enzymes. In conclusion,
      carbohydrate-rich foods typical of the Italian diet which are often consumed as
      an alternative to pasta dishes are not equivalent in terms of metabolic impact in
      diabetic patients. Due to their low blood glucose response, potato dumplings
      represent a valid alternative to other starchy foods in the diabetic diet. Food
      structure plays an important role in determining starch accessibility to
      digestion, thus influencing the postprandial blood glucose response.

PMID- 11227032
TI  - Eicosanoid production, thrombogenic ratio, and serum and LDL peroxides in normo-
      and hypercholesterolaemic post-menopausal women consuming two oleic acid-rich
      diets with different content of minor components.
AB  - The present paper compares the effects of two monounsaturated oils, extra virgin
      olive oil (EVOO) and high-oleic acid sunflower oil (HOSO), on serum and LDL
      peroxides, eicosanoid production and the thrombogenic ratio (thromboxane (TX)
      B2:6-keto-prostaglandin F1alpha) in fourteen non-obese post-menopausal women. The
      subjects, mean age 63 (SD 11) years, were assigned to two consecutive oleic acid
      rich 28 d dietary periods. EVOO and HOSO represented 62 % of the total lipid
      intake and were used as the only culinary fat during the first and second dietary
      periods respectively. Serum peroxides, plasma alpha-tocopherol and TXB2 levels in
      stimulated platelet-rich plasma (PRP-TXB2) were significantly higher (P < 0.01, P
      < 0.001, and P < 0.05, respectively) after the HOSO diet than after the EVOO
      diet. The relationship between the serum cholesterol level (< 6.21 mmol/l or > or
      = 6.21 mmol/l) and the type of dietary oil on eicosanoids, peroxides and alpha
      tocopherol were evaluated by two-way ANOVA. Dietary oil significantly affected (P
      < 0.05) the PRP-TXB2 level, whereas serum and LDL peroxides were significantly
      affected (P < 0.001 and P < 0.01, respectively) by the serum cholesterol level.
      The plasma alpha-tocopherol level was significantly affected by the serum
      cholesterol level and the type of dietary oil (both P < 0.001). No significant
      relationships were found between serum cholesterol levels, serum peroxide or LDL
      peroxide levels, plasma alpha-tocopherol concentrations or alpha-tocopherol
      intakes with eicosanoid production or the thrombogenic ratio due to dietary
      changes. However, in spite of their higher alpha-tocopherol levels,
      hypercholesterolaemic subjects showed increased peroxidation in serum and LDL in
      comparison with normocholesterolaemic subjects on the HOSO diet in comparison
      with the EVOO diet. These findings suggest that differences in the type of minor
      compounds, as well as in the concentration of linoleic acid, in both these
      monounsaturated oils may play an important role in modulating eicosanoid
      production and lipoprotein peroxidation when they constitute a large proportion
      of the diet of post-menopausal women.

PMID- 11227033
TI  - Longitudinal vitamin and homocysteine levels in normal pregnancy.
AB  - Evidence of the impact of maternal nutritional status on pregnancy outcome is
      increasing. However, reference values for vitamin and homocysteine concentrations
      in maternal blood during normal pregnancy are scarce, and are lacking for the
      preconceptional period and early pregnancy. Thus, in a longitudinal study we
      evaluated vitamin and homocysteine concentrations in 102 nulliparous women with
      an uneventful singleton pregnancy and normal outcome not using supplements. The
      physiological changes in vitamin and homocysteine concentrations in blood were
      determined from the preconceptional period throughout pregnancy until 6 weeks
      post-partum. The vitamins evaluated comprised retinol, thiamin, riboflavin,
      pyridoxal 5'-phosphate, folate in serum and erythrocytes, vitamin B12 and alpha
      tocopherol. The plasma homocysteine concentration was also measured, considering
      the essential roles of folate, vitamin B6 and vitamin B12 in homocysteine
      metabolism. The concentrations of retinol, thiamin, pyridoxal 5'-phosphate serum
      folate and vitamin B12 decreased during pregnancy. In contrast, the
      concentrations of riboflavin, alpha-tocopherol, and folate in erythrocytes
      increased or showed only minor changes. Homocysteine concentrations also remained
      approximately constant during pregnancy. These observations emphasize the
      importance of preconceptional and post-partum concentrations of vitamins in the
      evaluation of pregnancy-induced changes. These data have provided valuable
      reference values for vitamins and homocysteine before, during and after pregnancy
      in order to contribute to better diagnosis of maternal deficiencies and to study
      further the relationship between maternal vitamin status and adverse course and
      outcome of pregnancy.

PMID- 11227034
TI  - Iron absorption from experimental infant formulas based on pea (Pisum sativum)
      protein isolate: the effect of phytic acid and ascorbic acid.
AB  - Infant formula based on pea (Pisum sativum)-protein isolate has been suggested as
      an alternative to soybean formula in countries where soybean is not a native
      crop, or when soybean protein cannot be used due to allergic reactions or
      intolerances. In the present study, Fe absorption from experimental infant
      formulas based on pea-protein isolate was measured in healthy non-anaemic young
      women. The influence of phytic acid and ascorbic acid on Fe absorption was
      evaluated, using a stable-isotope technique based on incorporation of Fe stable
      isotope labels into erythrocytes 14 d after administration. Geometric mean Fe
      absorption increased from 20.7 (+1 SD 41.6, -1 SD 10.3) % to 33.1 (+1 SD 58.6, -1
      SD 18.7) %; (P < 0.0001; n 10) after enzymic degradation of virtually all phytic
      acid. Doubling the molar ratio Fe:ascorbic acid from 1:2.1 to 1:4.2 in the infant
      formula with native phytic acid content also increased Fe absorption
      significantly (P < 0.0001; n 10); geometric mean Fe absorption increased from
      14.8 (+1 SD 32.1, -1 SD 6.8) % to 22.1 (+1 SD 47.2, -1 SD 10.4) %. These results
      confirm the inhibitory and enhancing effects of phytic acid and ascorbic acid
      respectively on Fe absorption, but also indicate relatively high fractional Fe
      absorption from the pea-protein-based formulas. After adjusting for differences
      in Fe status, our data indicate that Fe absorption from dephytinised pea protein
      might be less inhibitory than dephytinised soybean protein as measured in a
      previous study (Hurrell et al. 1998).

PMID- 11227035
TI  - Influence of urbanisation on physical activity and dietary changes in Huli
      speaking population: a comparative study of village dwellers and migrants in
      urban settlements.
AB  - The influence of urbanisation on physical activity and dietary changes was
      examined in a Papua New Guinea Highland population. Adult male and female
      subjects (n 56) were selected, including twenty-seven rural villagers and twenty
      nine urban migrants. BMR was calculated from values measured in similar samples
      of Huli-speaking population, according to gender and body weight. Total daily
      energy expenditure (TEE) was assessed by 24 h heart rate (HR) monitoring (flex-HR
      method) and physical activity level (PAL) calculation was based on BMR. Energy,
      protein and fat intakes were measured by weighing food on a single day. Urban
      subjects were heavier and taller than their rural counterparts; significant
      differences were found in stature in men (P < 0.05) and body weight in women (P <
      0.05). Urban subjects had longer sedentary periods (HR < or = flex-HR) and
      shorter active periods (HR > flex-HR) than rural subjects. Consequently, the
      former had lower TEE and PAL than the latter; significant differences were found
      in women (TEE, P < 0.05, PAL, P < 0.01) but not in men. Total daily energy intake
      and TEE were well balanced (<7 %) in all groups, whereas protein and fat intakes
      were considerably higher in urban subjects than rural subjects. Reduced PAL and
      increased fat intake by urban dwellers may increase the risks of obesity and
      chronic degenerative diseases.

PMID- 11227036
TI  - Validation of the doubly-labelled water technique in the domestic dog (Canis
      familiaris).
AB  - We validated doubly-labelled water (DLW) by comparison to indirect calorimetry
      and food intake-mass balance in eight Labrador dogs (24-32 kg) over 4 d. We used
      several alternative equations for calculating CO2 production, based on the single
      and two-pool models and used two alternative methods for evaluating the
      elimination constants: two-sample and multiple-sampling. In all cases the DLW
      technique overestimated the direct estimate of CO2 production. The greatest
      overestimates occurred with the single-pool model. Using two samples, rather than
      multiple samples, to derive the elimination constants produced slightly more
      discrepant results. Discrepancies greatly exceeded the measured analytical
      precision of the DLW estimates. The higher values with DLW probably occurred
      because the dogs were extremely active during the 1 h in each 24 spent outside
      the chamber. Estimates of CO2 production from food intake-mass balance, which
      include this activity, produced a much closer comparison to DLW (lowest mean
      discrepancy 0.3 % using the observed group mean dilution space ratio and an
      assumption that the mass changes reflected changes in hydration for all except
      one animal). We recommend an equilibration time of 6 h and use of the two-pool
      model based on the observed population dilution space for future studies of
      energy demands in dogs of this body mass.

PMID- 11227038
TI  - Modelling heat production and energy balance in group-housed growing pigs exposed
      to low or high ambient temperatures.
AB  - The effects of ambient temperature (T; 12-29 degrees C), body weight (BW; 30-90
      kg) and metabolisable energy intake (ME) on components of energy balance were
      studied in seven groups of Pietrain x Large White barrows kept in a respiratory
      chamber. In Expt 1 (groups 1, 2 and 3), T varied in a cyclic way from 22 degrees
      C to 12 degrees C and then from 12 degrees C to 22 degrees C with three or four
      consecutive days at each of 22, 19, 16, 14 and 12 degrees C. Similarly, in Expt 2
      (groups 4, 5 and 6), T varied from 19 to 29 degrees C and then from 29 to 19
      degrees C with three or four consecutive days at each of 19, 22, 25, 27 and 29
      degrees C. In both experiments, pigs were offered feed ad libitum. In Expt 3,
      pigs (group 7) were exposed to the thermic conditions of Expt 1 but their feed
      allowance was adjusted on a BW basis to the ad libitum intake recorded at 19 and
      22 degrees C in Expt 1. Groups 1, 2, 4, 5 and 7 were used over two successive
      cycles with initial average BW of 37 kg at cycle 1 (four pigs per group) and 63
      kg at cycle 2 (three pigs per group). Groups 3 and 6 were studied at an
      intermediary stage of growth; their initial BW was 45 kg. The O2 and CO2
      concentrations, physical activity and feed intake were continuously and
      simultaneously measured and used to calculate total heat production (HP; HPtot),
      HP due to physical activity (HPact), activity-free HP (HP0), and thermic effect
      of feed. HP was modelled as a non-linear function with T, BW and ME as
      predictors. Results indicate that all components of HP were proportional to
      BW(0.60). Physical activity was minimal between 19 and 27 degrees C (8 % ME). The
      estimated lower critical temperature was 24 degrees C. Between 24 and 12 degrees
      C, total thermic effect of feed decreased from 31 to 16 % ME, but the short-term
      thermic effect of feed (5.1 % ME) remained constant. Equations for prediction of
      HPtot, HPact and HP0 according to BW, T and ME are proposed and evaluated
      according to literature values; values for the feed cost of thermoregulation in
      pigs are proposed.

PMID- 11227037
TI  - Effect of cold exposure on energy balance and liver respiratory capacity in post
      weaning rats fed a high-fat diet.
AB  - Variations in energy balance, body composition, and nutrient partitioning induced
      by high-fat feeding, cold exposure or by concomitant high-fat feeding and cold
      exposure were studied in young Wistar rats. Changes in hepatic metabolism as well
      as in serum free triiodothyronine and leptin levels were also evaluated. Rats
      were exposed to either 24 or 4 degrees C and fed either a low- or high-fat diet
      (10 % or 50 % energy respectively) for 2 weeks. Relative to low-fat feeding at 24
      degrees C, both energy intake and expenditure were increased by high-fat feeding
      or by cold exposure, and these changes were accompanied by increased serum
      triiodothyronine levels. In response to concomitant high-fat feeding and cold
      exposure, serum triiodothyronine tended to be further elevated, but no further
      increases in energy intake or energy expenditure were observed. Independently of
      diet, the increased energy expenditure in cold-exposed rats was not completely
      balanced by adaptive hyperphagia, with consequential reductions in protein and
      fat gain, accompanied by marked decreases in serum leptin. Furthermore, unlike
      high-fat feeding at 24 degrees C, cold exposure enhanced hepatic mitochondrial
      oxidative capacity both in the low-fat- and high-fat-fed groups. It is concluded
      that in this strain of young Wistar rats, despite similarly marked stimulation of
      energy expenditure by high-fat feeding at 24 degrees C, by cold exposure and by
      concomitant high-fat feeding and cold exposure, an increased hepatic oxidative
      capacity occurred only in the presence of the cold stimulus.

PMID- 11227039
TI  - Association of the maternal experience and changes in adiposity measured by BMI,
      waist:hip ratio and percentage body fat in urban Brazilian women.
AB  - The aim of the present study was to determine the association between the
      maternal experience and changes in adiposity measured by BMI, percentage body fat
      (PBF) and waist:hip ratio (WHR). In a cross-sectional study, 203 women were
      recruited at health care and educational facilities in Brasilia, Brazil. These
      women were divided into three groups: fifty-three nulliparous (no full-term
      pregnancy); sixty-three primiparous (one full-term pregnancy); eighty-seven
      multiparous (two or more full-term pregnancies). Socio-economic, behavioural,
      reproductive and dietary data were collected. All the women were measured for
      weight, height, skinfold thicknesses and waist and hip circumferences. Analysis
      of covariance was used to measure the differences among the three groups in
      relation to BMI, PBF, and WHR, controlling for the following covariates: age;
      socio-economic status; use of oral contraceptives; smoking; energy intake level;
      cooking oil intake; physical activity level; lactation score; parity. The three
      groups of women differed significantly for BMI (P = 0.04), PBF (P = 0.0008), and
      WHR (P = 0.0001). Multiparous women presented higher BMI (P = 0.01) and PBF (P =
      0.03) compared with primi- and nulliparous groups. PBF was also associated with
      age and high socio-economic status. Primi- and multiparous women showed a higher
      WHR than nulliparous women (P < 0.0001). Age and smoking habit were also factors
      associated with higher WHR.

PMID- 11227040
TI  - Manipulating the fatty acid composition of muscle and adipose tissue in beef
      cattle.
AB  - Enhancing the n-3 polyunsaturated fatty acid (PUFA) content of beef is important
      in view of the generally saturated nature of fatty acids in ruminant meats and
      the negative effect this can have on human health. This study examined the
      effects of different sources of dietary n-3 PUFA on the performance of steers and
      the fatty acid composition of m. longissimus thoracis muscle and associated
      subcutaneous adipose tissue. Animals were fed ad libitum on grass silage plus one
      of four concentrates (60:40 forage:concentrate on a DM basis) containing
      differing sources of lipid: Megalac (16:0), lightly bruised whole linseed (18:3n
      3), fish oil (20:5n-3 and 22:6n-3) and a mixture of linseed and fish oil (1:1, on
      an oil basis). Diets were formulated so that total dietary oil intake was 6 %,
      approximately half of which was from the experimental test oil. Linseed feeding
      not only increased the levels of 18:3n-3 in muscle phospholipid from 9.5 to 19
      mg/100 g muscle but also enhanced the synthesis of 20:5n-3, the level of which
      increased from 10 to 15 mg/100 g muscle. Linseed also increased the proportion of
      18:3n-3 in muscle neutral lipid and in adipose tissue lipids by a factor of 1.64
      and 1.75 respectively. Fish oil feeding doubled the proportion of 20:5n-3 and
      22:6n-3 in muscle phospholipids. The proportion of 18:1 trans in muscle neutral
      lipid was higher on the n-3 PUFA diets than the control diet, 0.04 and 0.02
      respectively. Despite the implied modification to rumen metabolism, lipid source
      did not affect feed intake, growth rate, cold carcass weight or carcass fatness,
      but carcass conformation score was higher on fish oil treatments (P < 0.05).
      However, total muscle fatty acid content was not different between treatments and
      ranged from 3.5-4.3 % of tissue weight. The increase in n-3 PUFA in the meat
      produced by feeding linseed or fish oil lowered the n-6:n-3 ratio but had little
      effect on the P:S ratio.

PMID- 11227041
TI  - Elevated acute-phase protein in stunted Nepali children reporting low morbidity:
      different rural and urban profiles.
AB  - This study examined the associations between severity of stunting, plasma protein
      concentrations and morbidity of 104 Nepali boys, aged 10-14 years, living in
      contrasting environments. Boys from a remote village were compared with three
      similarly aged urban groups: poor squatters, homeless street children, and middle
      class schoolchildren. All but the middle-class group were stunted, particularly
      village boys whose mean height-for-age z-score (-2.97, SD 0.82) indicates severe
      growth retardation. Stunting was significantly associated with increased plasma
      levels of the acute-phase protein alpha1-antichymotrypsin itself inversely
      related to plasma levels of albumin. Plasma ACT levels of village children (mean
      1.52 g/l, SD 0.43) were three to four times higher than those of squatters and
      homeless street children, and five times higher than those of middle-class boys.
      Despite being the most severely stunted and having the most abnormal plasma
      protein values, village children reported the lowest burden of disease, a
      contradiction which may reflect exposure to sub-clinical infections or
      habituation to illness and low expectation of treatment. This study draws
      attention to the strikingly high levels of ACT and of stunting in the rural
      sample, and cautions on the use of uncorroborated morbidity reports across
      different epidemiological and socio-ecological environments. Possible mechanisms
      to explain the impact of illness and inflammation on growth faltering are
      discussed.

PMID- 11227042
TI  - Is there a future for renin inhibitors?
AB  - Pharmacological interruption of the renin-angiotensin system is possible at three
      major sites, the angiotensin-converting enzyme (ACE), the AT1 receptor and at the
      interaction of renin with its substrate, angiotensinogen. Skeggs and his
      associates in 1957 argued logically but without prognostic accuracy that 'since
      renin is the initial and rate-limiting substance in the renin-angiotensin system,
      it would seem that the renin inhibition approach would be the most likely to
      succeed'. In fact, the development of agents that act at all three levels has
      enjoyed substantial success, yet renin inhibition, which showed early progress in
      studies in humans, has languished. Our task in this essay is to review the
      reasons for the slow evolution of renin inhibition and to discuss the potential
      of such agents in modern pharmacotherapy. All of the structure-action
      relationships have involved variation on the original peptide structure. The
      possibility that alternative approaches based on x-ray crystallography and
      reconstruction of the structure of the active site would lead to novel agents,
      appears not to have been explored systematically. This opportunity is all the
      more attractive because renin is one of the few targets that is actually soluble
      and amenable to x-ray crystallographic studies. At the moment, it appears that
      all renin inhibitor development programs have been closed, although hints
      periodically reappear to indicate that one company or another is pursuing a novel
      agent. The decision to close programs seems to have reflected not the therapeutic
      potential of renin inhibitors, but rather the cost of their synthesis, continuing
      problems with bioavailability and the remarkable success of the competitor class-
      the AngII antagonists. We believe that the potential of renin inhibition in human
      therapy has been under estimated and still shows substantial promise.

PMID- 11227043
TI  - Novel approaches to treating cardiovascular disease: lessons from Tangier
      disease.
AB  - Atherosclerotic cardiovascular disease (CVD) remains the leading cause of
      morbidity and mortality in Western societies. Although cholesterol is a major CVD
      risk factor, therapeutic interventions to lower plasma cholesterol levels have
      had limited success in reducing coronary events. Thus, novel approaches are
      needed to reduce or eliminate CVD. A potential therapeutic target is a newly
      discovered ATP binding cassette transporter called ABCA1, a cell membrane protein
      that is the gateway for secretion of excess cholesterol from macrophages into the
      high density lipoprotein (HDL) metabolic pathway. Mutations in ABCA1 cause
      Tangier disease, a severe HDL deficiency syndrome characterised by accumulation
      of cholesterol in tissue macrophages and prevalent atherosclerosis. Studies of
      Tangier disease heterozygotes revealed that the relative activity of ABCA1
      determines plasma HDL levels and susceptibility to CVD. Drugs that induce ABCA1
      in mice increase clearance of cholesterol from tissues and inhibit intestinal
      absorption of dietary cholesterol. Thus, ABCA1-stimulating drugs have the
      potential to both mobilise cholesterol from atherosclerotic lesions and eliminate
      cholesterol from the body. By reducing plaque formation and rupture independently
      of the atherogenic factors involved, these drugs would be powerful agents for
      treating CVD.

PMID- 11227044
TI  - Glycogen phosphorylase inhibitors for treatment of type 2 diabetes mellitus.
AB  - Type 2 diabetes mellitus is a severe disease with large economic consequences,
      which is significantly under-diagnosed and incompletely treated in the general
      population. Control of blood glucose levels is a key objective in treating
      diabetic patients, who are most often prescribed one or more oral hypoglycaemic
      agents in addition to diet and exercise modification as well as insulin. In spite
      of the availability of different classes of hypoglycaemic drugs, treatment
      regimens are often unable to achieve an intensive degree of glucose control known
      to most effectively reduce the incidence and severity of diabetic complications.
      Hepatic glucose output is elevated in type 2 diabetic patients and current
      evidence indicates that glycogenolysis (release of monomeric glucose from the
      glycogen polymer storage form) is an important contributor to the abnormally high
      production of glucose by the liver. Glycogen phosphorylase is the enzyme that
      catalyses this release and recent advances in new inhibitors of this structurally
      and kinetically well studied enzyme have enabled work which further delineate the
      pharmacological and physiological consequences of inhibiting glucose production
      by this pathway. Most notably, these agents lower glucose in diabetic animal
      models, both acutely and chronically, appear to affect both gluconeogenic and
      glycogenolytic pathways and demonstrate potential for a beneficial effect on
      cardiovascular risk factors. Cumulatively, this information has bolstered
      interest and promise in glycogen phosphorylase inhibitors (GPIs) as potential new
      hypoglycaemic agents for treatment of type 2 diabetes mellitus.

PMID- 11227045
TI  - Substrate reduction therapy for glycosphingolipid storage disorders.
AB  - Substrate reduction therapy is a novel approach to treating glycosphingolipid
      (GSL) lysosomal storage disorders. These diseases are caused by mutations in the
      genes coding for enzymes involved in GSL catabolism and are characterised by the
      accumulation of GSL substrates within the lysosomes of cells. The aim of
      substrate reduction therapy is to inhibit the rate of synthesis of GSLs to levels
      where the residual activity of the mutant catabolic enzyme is sufficient to
      prevent pathological storage. In this review we discuss the development of N
      butyldeoxynojirimycin (NB-DNJ), an imino sugar that inhibits the ceramide
      specific glucosyltransferase which catalyses the first committed step of GSL
      synthesis. This agent has been shown to slow accumulation of stored glycolipid in
      an in vitro model of Gaucher's disease and in knockout mouse models of Tay-Sachs
      and Sandhoff diseases. Furthermore, administration of NB-DNJ to Sandhoff mice
      delays the onset of neurological disease and also slows its progression. We
      discuss safety and efficacy data from the clinical trial of substrate reduction
      with NB-DNJ which has been undertaken in patients with Type 1 Gaucher's disease.
      This trial provides a proof-of-principle for the use of this approach in a wide
      range of GSL lysosomal storage diseases.

PMID- 11227046
TI  - The immunotherapeutic potential of melatonin.
AB  - The interaction between the brain and the immune system is essential for the
      adaptive response of an organism against environmental challenges. In this
      context, the pineal neurohormone melatonin (MEL) plays an important role. T
      helper cells express G-protein coupled cell membrane MEL receptors and, perhaps,
      MEL nuclear receptors. Activation of MEL receptors enhances the release of T
      helper cell Type 1 (Th1) cytokines, such as gamma-interferon (gamma-IFN) and IL
      2, as well as of novel opioid cytokines. MEL has been reported also to enhance
      the production of IL-1, IL-6 and IL-12 in human monocytes. These mediators may
      counteract stress-induced immunodepression and other secondary immunodeficiencies
      and protect mice against lethal viral encephalitis, bacterial diseases and septic
      shock. Therefore, MEL has interesting immunotherapeutic potential in both viral
      and bacterial infections. MEL may also influence haemopoiesis either by
      stimulating haemopoietic cytokines, including opioids, or by directly affecting
      specific progenitor cells such as pre-B cells, monocytes and NK cells. MEL may
      thus be used to stimulate the immune response during viral and bacterial
      infections as well as to strengthen the immune reactivity as a prophylactic
      procedure. In both mice and cancer patients, the haemopoietic effect of MEL may
      diminish the toxicity associated with common chemotherapeutic protocols. Through
      its pro-inflammatory action, MEL may play an adverse role in autoimmune diseases.
      Rheumatoid arthritis patients have increased nocturnal plasma levels of MEL and
      their synovial macrophages respond to MEL with an increased production of IL-12
      and nitric oxide (NO). In these patients, inhibition of MEL synthesis or use of
      MEL antagonists might have a therapeutic effect. In other diseases such as
      multiple sclerosis the role of MEL is controversial. However, the correct
      therapeutic use of MEL or MEL antagonists should be based on a complete
      understanding of their mechanism of action. It is not yet clear whether MEL acts
      only on Th1 cells or also on T-helper Type 2 cells (Th2). This is an important
      point as the Th1/Th2 balance is of crucial importance in the immune system
      homeostasis. Furthermore, MEL being the endocrine messenger of darkness, its
      endogenous synthesis depends on the photoperiod and shows seasonal variations.
      Similarly, the pharmacological effects of MEL might also be season-dependent. No
      information is available concerning this point. Therefore, studies are needed to
      investigate whether the immunotherapeutic effect of MEL changes with the
      alternating seasons.

PMID- 11227047
TI  - Testosterone in ageing men.
AB  - A progressive decline in androgen levels is a common finding in men after middle
      age. The resulting clinical picture may be characterised by alterations in the
      physical and psychological domains, which have been demonstrated to correlate
      positively with testosterone serum levels. This clinical picture closely
      resembles the features of primary or secondary hypogonadism. Testosterone is the
      more convenient hormone for substitution therapy in classic hypogonadism as well
      as in age-related hypoandrogenism. Different choices of testosterone preparations
      are currently available, which are characterised by different routes of
      administration and by various pharmacokinetic profiles. Two major achievements
      urgently need to be investigated in the near future: the ability of the new
      formulations to reach more physiological and sustained hormone levels with the
      concomitant amelioration of their tolerability and the evidence of long-term
      prospective studies aimed at demonstrating the benefits and the possible
      complications of this therapy.

PMID- 11227048
TI  - Hormonal treatment for prostate cancer.
AB  - For nearly six decades the preferred primary treatment for advanced prostate
      cancer has been continuous suppression of testicular androgen production by
      medical or surgical castration. While androgen deprivation is effective in
      inducing tumour regression in the large majority of cases, essentially all
      patients will develop progressive disease. In addition androgen deprivation may
      be associated with a variety of side effects. Thus, strategies that minimise the
      use of these agents could potentially lower the morbidity and cost associated
      with the treatment of advanced prostate cancer. In the era of prostate-specific
      antigen (PSA) testing, hormonal therapy is being used earlier in the course of
      the disease when the only evidence of recurrent disease is an elevated PSA. These
      men may survive for many years and thus have the potential for long periods of
      exposure to hormonal therapy and its side effects. It has been hoped that the
      development of alternative hormonal interventions might lead to both enhanced
      antitumour efficacy as well as improvements in side effect profile.

PMID- 11227049
TI  - PSMA specific antibodies and their diagnostic and therapeutic use.
AB  - Prostate-specific membrane antigen (PSMA) is a membrane-bound glycoprotein highly
      restricted to prostatic epithelial cells. PSMA expression is increased in
      association with prostatic cancer, particularly in hormone refractory disease.
      Given its membrane-bound character, PSMA is an ideal sentinel molecule for use in
      targeting prostatic cancer cells. Monoclonal antibodies specific for PSMA are
      available, beginning with the antibody 7E11.C5 which originally defined PSMA and
      which has been developed for use in cancer detection via immunoscintiscanning in
      the ProstaScint test. Newer second generation antibodies specific for both linear
      amino acid sequence epitopes and protein conformational epitopes on the
      extracellular domain of PSMA have been reported. Although most of these are
      murine antibodies, both humanised and fully human examples have been developed.
      These antibodies are beginning to work their way into clinical applications for
      potential improved diagnostic and therapeutic uses. Results to date suggest that
      antibodies specific for extracellular epitopes are significantly better for
      clinical uses in vivo than the 7E11.C5 antibody that is specific for an
      intracellular epitope. Current knowledge relating to PSMA-specific antibodies and
      their clinical uses and potential is described and evaluated.

PMID- 11227050
TI  - New agents for the medical treatment of interstitial cystitis.
AB  - Interstitial cystitis (IC) is a painful, sterile, disorder of the urinary bladder
      characterised by urgency, frequency, nocturia and pain. IC occurs primarily in
      women but also in men with recent findings indicating that chronic, abacterial
      prostatitis may be a variant of this condition. The prevalence of IC has ranged
      from about 8 - 60 cases/100,000 female patients depending on the population
      evaluated. About 10% of patients have severe symptoms that are associated with
      Hunner's ulcers on bladder biopsy; the rest could be grouped in those with or
      without bladder inflammation. Symptoms of IC are exacerbated by stress, certain
      foods and ovulatory hormones. Many patients also experience allergies, irritable
      bowel syndrome (IBS) and migraines. There have been various reports indicating
      dysfunction of the bladder glycosaminoglycan (GAG) protective layer and many
      publications showing a high number of activated bladder mast cells. Increasing
      evidence suggests that neurogenic inflammation and/or neuropathic pain is a major
      component of IC pathophysiology. Approved treatments so far include intravesical
      administration of dimethylsulphoxide (DMSO) or oral pentosanpolysulphate (PPS).
      New treatments focus on the combined use of drugs that modulate bladder sensory
      nerve stimulation (neurolytic agents), inhibit neurogenic activation of mast
      cells, or provide urothelial cytoprotection, together with new drugs with anti
      inflammatory activity.

PMID- 11227052
TI  - [Possibilities of cell culture methods and alternatives to animal tests in
      toxicology]
AB  - A current basic shift in the ethical, scientific and commercial engagement for
      alternatives to animal experimentation is described which is a prerequisite for
      their stronger use in practice. A review on the various alternatives is given
      with emphasis on cell culture methods and toxicology. The most promising
      alternatives are prospectively summarized and some known limits of in vitro
      systems are discussed in comparison with the value of results from animal
      experimentation and in the context of safety evaluations in toxicology.

PMID- 11227051
TI  - New pharmacological agents under clinical investigation for treating disorders of
      lipoprotein regulation leading to atherosclerosis.
AB  - Coronary heart disease (CHD), whose primary aetiology is atherosclerosis, is the
      leading cause of mortality and a major cause of morbidity in the industrialised
      world [1]. Serum lipoprotein levels are aetiologically related to the risk of
      atherosclerosis and CHD [2]. The liver and the gastrointestinal system are the
      major protagonists involved in regulation of lipoprotein biochemical
      physiological mechanisms and the development of hypercholesterolaemia.
      Furthermore, specific lipoprotein receptors are being discovered as targets for
      pharmacological intervention to correct lipoprotein disorders. Agents that target
      lipoprotein regulation in the liver, gastrointestinal-biliary and atherosclerotic
      tissues resulting in improved serum lipoprotein levels and/or control of primary
      and secondary dyslipidaemic disorders including diabetes, are currently
      undergoing clinical trials. The most novel promising compounds, after the greatly
      effective newest HMG-CoA reductase inhibitors, are drugs that affect peroxisome
      proliferator-activated receptors, PPARalpha and PPARgamma receptors, bile acid
      transport mechanisms, cholesterol absorption and cholesterol acyltransferase and
      other biochemical targets of lipoprotein regulation. Current knowledge and
      ongoing trials with these agents are described here within the boundaries of
      investigator confidentiality agreements.

PMID- 11227053
TI  - [Mass Production of Monoclonal Antibodies: Technical, Scientific and Ethical
      Considerations]
AB  - The mass production of monoclonal antibodies (MABs) becomes more important in the
      near future, in contrast to microorganisms, the antibody-producing hybridomas are
      very sensitive to the culture conditions in mass cell culture and therefore
      difficult to cultivate in bulk quantities. The most common in vitro and in vivo
      systems for the production of monoclonal antibodies in bulk preparations are
      discussed. For the mass production of monoclonal antibodies, several in vitro
      systems are in use or under development today: 1. Spinner flasks represent the
      most simple culture system for producing antibodies. Various mixing devices were
      developed and different culture media were used for an efficient growth of the
      cells. 2. Several fermenters exist for the growth of hybridoma cells and
      production of MABs with all kind of stirrers, mixing devices and electronic
      control equipment. It is proposed that the "dialysis fermenter" will be the
      favorite equipment for future mass production of MABs. 3. The capillary
      bioreactor is efficient for the production of MABs in small quantities. High cell
      densities and good quality of the harvested MABs can be achieved. 4. The most
      common production system is still the in vivo production of MABs in the ascites
      fluid of mice. Technical and ethical aspects of this in vivo production are
      discussed in the light of the new German law for the protection of animals in
      biomedical experiments.

PMID- 11227054
TI  - [Development of small-diameter vascular prostheses covered with human endothelial
      cells: Possibilities and limits of in vitro-tests]
AB  - There is an increasing demand for small-diameter vascular prostheses for the
      replacement of arteriosclerotic coronary arteries. They may be replaced by
      autologous blood vessels, usually parts of the saphenous vein. Prostheses of
      synthetic materials and an inner diameter of less than 4 to 6 mm are
      unsatisfactory and, therefore, not implanted for coronary arteries. A substantial
      improvement is, however, expected for prostheses covered with human autologous
      endothelial cells. It has to be proved that this new type of vascular prostheses
      is an adequate replacement for small arteries. Tests of the new prosthesis should
      comprise cell and tissue compatibility of the synthetic materials as well as
      normal function of the endothelial cells. The aim of the present paper was to
      reduce the number of animal experiments in this development by establishing new
      in vitro tests for endothelial cell compatibility of synthetic materials and for
      the adherence of endothelial cell on the prosthesis. Physiologically haemodynamic
      streaming conditions are in vitro produced by self-constructed circulatory
      systems. First results demonstrate that physiologic shear stress is achieved.
      Limits and relevance of the in vitro tests are discussed in relation to animal
      experiments and clinical studies.

PMID- 11227055
TI  - [Intercellular communication and Tumor Invasion in the Petri Dish]
AB  - Malignant tumor cells are characterized by their ability to invade and destroy
      normal tissues, whereas benign tumor cells grow locally and, therefore, can be
      treated with more success. Tumor cell invasion proceeds the formation of
      metastases, which account for the high mortality of cancer patients. We
      investigated whether tumor cells which communicate via trans-membrane channels
      (gap junctions) with each other as well as with normal cells can more easily
      invade normal tissues than non-communicating tumor cells. Five tumor cell lines
      were cultured as monolayers and investigated with histological methods for gap
      junction formation and with electrophysiological methods for intercellular
      communication. Tumor cells were tested with an in vitro invasion model:
      spheroidal cell aggregates of normal and of malignant cells were confronted in
      petri dishes and co-cultured for varying time spans. Thin sections revealed that
      only tumor cells with gap junctions can actively invade aggregates of normal
      cells. Tumor cells without gap junctions are unable to invade the normal tissue:
      they may, however, destroy the normal cells by a completely different mechanism
      which may be a result of particular culture conditions.

PMID- 11227056
TI  - [Use of hepatocyte cultures in toxicology]
AB  - The significance of hepatocyte cultures as an alternative to animal tests in
      experimental toxicology and routine safety assessment of drugs and chemicals has
      increased during the past years. Practical applications for cytotoxicity testing
      of compounds range from the analysis of specific cellular mechanisms of toxicity
      to the determination of species differences (including man) for a given endpoint,
      and the screening of structural analogs. Hepatocyte cultures have been
      successfully used to assess genotoxicity by demonstrating various types of DNA
      damage. They are also used as a metabolic system for different genotoxicity
      assays. Using the techniques, specific information can be obtained which may be
      equivalent or even superior (e.g. when using human hepatocytes) to the answers
      provided by in vivo experiments. However, hepatocyte cultures should only be used
      as a complementary method in combination with animal experiments in order to
      optimally predict the hepatotoxic potential of drugs and chemical in man.

PMID- 11227057
TI  - [Enzymes of the Xenobiotic Metabolism of Continuous Cell Lines in invitro
      Toxicity Testing]
AB  - Cells in continuous culture contain a large number of enzymes which are involved
      in the metabolism of potentially toxic chemicals. As a rule, the activities of
      these enzymes represent functions of low tussle specificity. In contrast, those
      functions which are specialized "differentiated" functions in vivo are no longer
      expressed in continuous cell lines. However, an increasing number of observations
      indicates that cell lines may also contain these functions. Cell lines which lack
      or possess specific xenobiotic metabolizing enzymes are already applicable for
      analyzing the complex mechanisms of activation and inactivation of chemicals.
      With a better understanding how differentiated cell functions are regulated,
      prospects are promising for establishing metabolically competent cell lines,
      which can also be used in the screening of toxic chemicals.

PMID- 11227058
TI  - [Anxiety and Reduction of Anxiety in Animal Experiments]
AB  - Laboratory animals usually respond to new situations with anxiety and distress.
      This can strongly influence the results of an experiment, thereby defeating the
      very purpose of the experiment. For this reason as well as because of aspects of
      animal welfare, methods for minimizing anxiety of laboratory animals should be
      investigated. With relatively little effort the animals can be accustomed to the
      experimental situation. Proper handling is a way to reduce their anxiety.

PMID- 11227059
TI  - [Roller Chamber Technique in Cell Toxicology]
AB  - A cell culture procedure has been developed which permits target and liver cells
      to be co-cultured on separate standard culture dishes. The cultures are connected
      in a closed chamber which makes experiments with volatile substances possible.
      The chamber is slowly rotated to ensure good physiological conditions during
      incubation. In this system the effects of cyclophosphamide, acrylamide, n-hexane,
      2,5-hexanidione, carbon tetrachcloride, allyl alcohol, and an experimental
      substance (H200/68) on cells from the nervous system have been investigated.
      Toxic effects have been registered as changes in cell growth rate and rate of
      protein synthesis. The results show that liver cell mediated alteration in
      toxicity can be studied successfully using the roller chamber co-culture method.
      The present paper is a combination of results obtained within several projects
      either aimed at the development of the roller chamber technique or having in view
      to address certain toxicological problems.

PMID- 11227060
TI  - [Aggregate cell cultures]
AB  - Aggregate cultures are primary cell cultures prepared from dissociated fetal
      cells. In rotation-mediated culture under rigorously controlled conditions, the
      isolated cells are able to reaggregate spontaneously, and to form a large number
      of practically identical spheres. The three-dimensional cell structure in each
      aggregate provides a maximum of cell-cell interactions, and thus enables the
      cells to rearrange and to develop in an organotypic fashion. Relatively simple
      techniques are now available which permit the preparation of aggregate cultures
      from fetal brain and liver cells. Since they can be grown in a chemically defined
      medium, and because they mimic several morphogenetic events occurring in vivo,
      these cultures offer a unique model for developmental studies. Moreover, they may
      be used as well for routine testing, for example for screening purposes in
      toxicology, and thus contribute to the reduction of animal experiments.

PMID- 11227061
TI  - [Development of hepatocyte cultures in toxicity testing]
AB  - The liver plays a key role in drug and xenobiotic metabolism. The probability of
      detecting the toxicity of unknown chemicals in vitro is therefore highest in
      liver cell cultures. In culture however, enzymes involved in xenobiotic
      metabolism are preferentially degraded within one to two days. In order to
      improve this situation, investigations were focused on the maintenance of a
      tissue-like oxygen tension and the maintenance of xenobiotic metabolism by means
      of heterotypic cell cultures. In conventional culture dishes, as a function of
      cell density, the oxygen diffusion is delayed and depleted. Using teflon membrane
      culture dishes, a stable, incubator-controlled, tissue like oxygen tension of 4%
      and 13% O2 respectively, was achieved. In co-cultures of hepatocytes, the
      auxiliary cells selected from livers of 10 day old rats maintained the liver cell
      specific cytochrome P-450 dependent aldrin epoxidase up to one week, to 40% of
      the original value. The analysis of cellular DNA and protein content in
      hepatocytes by flow cytometry revealed specific ploidy shifts inducible by low
      oxygen tension, by fetal calf serum, by phenobarbital and dimethylsulfoxide.
      Chemically induced alterations in ploidy might be an indicator to detect
      compounds which interfere with growth and differentiation of hepatocytes in
      culture.

PMID- 11227062
TI  - Brief Strategic Family Therapy: twenty-five years of interplay among theory,
      research and practice in adolescent behavior problems and drug abuse.
AB  - This article describes a systematic program of research that focuses on Brief
      Strategic Family Therapy (BSFT) and the adaptations that were developed based on
      BSFT principles. The culture-specific origins of BSFT are reviewed, as well as
      its broader applications to the field of family therapy. Research is reviewed
      demonstrating that BSFT is a promising family-based approach to treating Hispanic
      youth behavior problems and drug abuse. Treatment innovations are described that
      address the combination of intergenerational and cultural differences that occur
      among youths and their Hispanic parents. Programmatic work is described that
      challenges basic principles of family therapy by expanding BSFT to a One Person
      modality and a strategic engagement procedure. Both of these novel approaches are
      intended to add tools to therapists' repertoire in working with difficult-to
      engage families. A preview discussion of results is presented from a randomized
      clinical trial that is an application of an ecosystemic prevention version of
      BSFT. The implications of the work of the Center for Family Studies are discussed
      in the context of the broader service system. Ultimately, this article
      articulates a way of thinking about adolescent problem behavior, its social
      interactional determinants, and a range of theoretically consistent family
      centered strategies that attempt to change social ecological processes that
      impact adolescent developmental trajectories.

PMID- 11227063
TI  - The role of families in adolescent HIV prevention: a review.
AB  - Recent research has highlighted the significant contribution families make in the
      prevention of HIV risk behaviors among adolescents. As the most proximal and
      fundamental social system influencing child development, families provide many of
      the factors that protect adolescents from engaging in sexual risk behaviors.
      Among these are positive family relations, effective communication about
      sexuality and safer sexual behaviors, enhancement and support of academic
      functioning, and monitoring of peer activities. HIV risk behaviors occur in a
      social context, and it is becoming clear that the earliest and most effective way
      to intervene is in the context where one initially learns about relationships and
      behavior--the family. Both the Centers for Disease Control and Prevention and the
      National Institute for Mental Health have taken steps to support and emphasize
      research that will further elucidate our understanding of the role of families in
      HIV prevention. This article uses Ecodevelopmental Theory to guide and organize
      the findings of this promising research area. Within this context, and with
      special attention to the comorbidity of adolescent problem behaviors, this
      article reviews empirical research on the role of families in HIV prevention,
      discusses current intervention efforts that involve families and ecosystems, and
      addresses prospects and implications for future research and interventions.

PMID- 11227064
TI  - Children who murder: a review.
AB  - Despite considerable research on juvenile homicide, pre-adolescent homicide
      offenders have received less attention. This paper reviews the existing
      literature on preteen murderers in order to characterize the current state of
      research knowledge about this population, and draws on some of the work on
      adolescent homicide as well. The analysis of this literature considers historical
      context, methodological issues, previous attempts to classify youthful homicide
      offenders, and predictors of preteen homicidal behavior. While there is a high
      degree of heterogeneity within this population, several developmental
      similarities emerged across cases that were associated with the perpetration of
      homicide by preteens. A high percentage of preteen homicide offenders come from
      homes characterized by physical abuse, domestic violence, poor or absent
      parenting, and overall instability. Gun availability may have been a facilitating
      factor. Support for different etiologies of preteen versus adolescent homicide is
      weak. Recommendations for future research directions are offered.

PMID- 11227066
TI  - Molecular approaches to identification of tissue contamination in surgical
      pathology sections.
AB  - The finding of possibly contaminant tissues or cells in surgical or cytology case
      material can be a challenging problem in diagnostic anatomical pathology samples.
      The reported rates of occurrence have ranged from 0 to 8.8% (including
      prospective and retrospective cases). A diagnostically dissimilar tissue
      fragment, whether contiguous with other tissue or among other fragments within a
      paraffin section, and which is not incompatible with the case tissue, often
      requires a rigorous investigation to confirm or deny its relevance to the case.
      Fluorescence in situ hybridization using dual red and green DNA probes to regions
      of the X and Y chromosomes, respectively, were used in one case where the
      potential contaminant was suspected to have originated from a male patient. The
      putative contaminant tissue fragment was confirmed as male, with cells having one
      X and one Y chromosome, unlike the other tissue fragments on the slide with two X
      chromosomes. In a second case, DNA polymorphisms were used to compare allelic
      patterns that were informative not only in proving the extraneous tissue as a
      contaminant, but in addition, could be used to trace the latter to its original
      tissue source. The molecular tools of fluorescence in situ hybridization in sex
      mismatched cases and of DNA microsatellite probes that are applicable to paraffin
      sections can provide definitive identifiers of tissues and individual cells. They
      are important adjuncts to histology for the anatomical pathologist when faced
      with the diagnostic problems of tissue contamination encountered in routine
      practice.

PMID- 11227065
TI  - Molecular diagnosis of Epstein-Barr virus-related diseases.
AB  - Epstein-Barr virus (EBV) is the causative agent of infectious mononucleosis, and
      it may also be found in a wide variety of benign and malignant lesions including
      oral hairy leukoplakia, inflammatory pseudotumor, Hodgkin's disease, non
      Hodgkin's lymphoma, nasopharyngeal carcinoma, and gastric carcinoma. Molecular
      testing is increasingly important in the diagnosis and monitoring of patients
      affected by these diseases. In biopsy tissues, molecular detection of EBV-encoded
      RNA transcripts by in situ hybridization remains the gold standard for proving
      that a histopathological lesion is EBV-related. EBV-encoded RNA hybridization and
      EBV LMP1 immunostains are used routinely to detect latent EBV in tissues affected
      by posttransplant lymphoproliferative disorder (PTLD) or in enlarged nodes from
      patients with infectious mononucleosis. Traditional serology is the best test for
      evaluating acute versus remote infection in healthy individuals. High serological
      titers serve as a tumor marker for some EBV-related malignancies, but titers are
      not a dependable tumor marker in immunocompromised hosts. EBV viral load testing
      by quantitative DNA amplification of blood samples is a promising new laboratory
      test that has proven useful for early diagnosis and monitoring patients with
      PTLD. Recent studies suggest a role for EBV viral load testing in nasopharyngeal
      carcinoma, Hodgkin's disease, and AIDS patients with brain lymphoma. Further
      research is needed to define more fully the clinical utility of viral load tests
      in the full spectrum of EBV-associated diseases. Gene expression profiling is on
      the horizon as a means to improve subclassification of EBV-related diseases and
      to predict response to therapy.

PMID- 11227067
TI  - Extra copies of chromosomes 7, 8, 12, 19, and 21 are recurrent in adamantinoma.
AB  - Adamantinoma of long bones is a rare neoplasm predominantly involving the tibia.
      Cytogenetic studies of adamantinoma are few. Cytogenetic or molecular cytogenetic
      analysis of four adamantinomas, and a review of eleven cases in the literature
      reveals extra copies of chromosomes 7, 8, 12, 19, and 21 as recurrent in this
      neoplasm. Adamantinoma may be confused with a variety of primary and metastatic
      epithelial and mesenchymal neoplasms. Observation of these aneuploidies may be
      useful in establishing the diagnosis of adamantinoma.

PMID- 11227068
TI  - Quantitative amplification of genomic DNA from histological tissue sections after
      staining with nuclear dyes and laser capture microdissection.
AB  - Laser capture microdissection (LCM) allows the selective sampling of tissue from
      histological sections. A prerequisite for this technique is the availability of
      histological dyes that do not interfere with downstream analysis of the sampled
      genetic material. We have examined the effect of four histological nuclear dyes
      (methyl green, hematoxylin, toluidine blue O, azure B) on TaqMan polymerase chain
      reaction amplification of beta-actin genomic DNA prepared from fixed and frozen
      tissue. Tissue sampled from the histological sections by manual dissection was
      compared with tissue sampled by LCM. As previously reported, when manually
      dissected tissue sections were analyzed, polymerase chain reaction amplification
      of DNA after hematoxylin staining was inferior to that after staining with the
      other dyes. In contrast, when tissue sampled by LCM was examined, DNA recovery
      after hematoxylin staining was equivalent to the recovery after methyl green
      staining. We conclude that DNA recovery from LCM-sampled tissue is independent of
      the histological stain chosen to highlight nuclear detail.

PMID- 11227069
TI  - Validation of array-based gene expression profiles by real-time (kinetic) RT-PCR.
AB  - We evaluated real-time (kinetic) reverse transcription-polymerase chain reaction
      (RT-PCR) to validate differentially expressed genes identified by DNA arrays.
      Gene expression of two keratinocyte subclones differing in the physical state of
      human papillomavirus (episomal or integrated) was used as a model system. High
      density filter arrays identified 444 of 588 genes as either negative or expressed
      with less than twofold difference, and the other 144 genes as expressed uniquely
      or with more than twofold difference between the two subclones. Real-time RT-PCR
      used LightCycler-based SYBR Green I dye detection and melting curve analysis to
      validate the relative change in gene expression. Real-time RT-PCR confirmed the
      change in expression of 17 of 24 (71%) genes identified by high-density filter
      arrays. Genes with strong hybridization signals and at least twofold difference
      were likely to be validated by real-time RT-PCR. This data suggests that (i) both
      hybridization intensity and the level of differential expression determine the
      likelihood of validating high-density filter array results and (ii) genes
      identified by DNA arrays with a two- to fourfold difference in expression cannot
      be eliminated as false nor be accepted as true without validation. Real-time RT
      PCR based on LightCycler technology is well-suited to validate DNA array results
      because it is quantitative, rapid, and requires 1000-fold less RNA than
      conventional assays.

PMID- 11227070
TI  - Polymerase chain reaction detection of Kaposi's sarcoma-associated herpesvirus
      optimized protocols and their application to myeloma.
AB  - Since its discovery in 1994, KSHV (also called human herpesvirus-8 or HHV8) has
      been implicated in a variety of disorders. Although the association of KSHV with
      Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric
      Castleman's disease has been well established, its presence in some other
      diseases, such as multiple myeloma, remains controversial. Because most KSHV
      studies are based on polymerase chain reaction (PCR) analysis, the conflicting
      data may be attributable to variations in the methods, primer sets, and target
      sequences selected. To establish an efficient and reliable PCR approach for KSHV
      detection we designed eight sets of primers to six regions (ORFK1, ORFK2, ORFK9,
      ORK26, ORF72, and ORF74) of the KSHV genome using appropriate database and
      software. The detection sensitivity of these primers was carefully assessed and
      their reliability was strictly validated in a series of positive (15 KS and PEL
      samples) and negative (16 lymphoid tissues) controls. We found that primer sets
      to the ORFK9 region showed the highest sensitivity, whereas primer sets to ORFK1
      and ORF74 showed the lowest sensitivity. Primer sets to ORFK9, ORF26 and ORF72
      regions detected all of the positive cases, whereas other primer sets showed
      varying detection rates or nonspecific bands. All 16 negative controls were
      negative with all primer sets. However, six of 16 negative controls became
      positive when we used nested PCR targeting ORF26. Therefore, multiple target KSHV
      sequences increase the detection efficiency, while nested PCR protocols are
      likely to introduce false positivity. Using ORFK9, ORF26 and ORF72 primer sets,
      we screened bone marrow biopsies from 18 cases of multiple myeloma, and failed to
      detect any KSHV sequences. This finding supports the conclusion that KSHV is not
      associated with multiple myeloma. Indeed, our results further confirm that
      although KSHV is universally present in Kaposi's sarcoma and primary effusion
      lymphoma, it is not ubiquitious.

PMID- 11227071
TI  - Toward a transactional conceptualization of oppositional defiant disorder:
      implications for assessment and treatment.
AB  - The conceptualization and treatment of oppositional defiant disorder (ODD) has
      been characterized by surprising homogeneity. In this paper evidence is presented
      to underscore the heterogeneity within ODD, including research demonstrating (a)
      the distinction between reactive and proactive forms of aggression; (b) the
      importance of affective modulation and self-regulation, and associated cognitive
      skills, in the development of the skill of compliance; and (c) high levels of
      comorbidity between ODD and other disorders. The disparate pathways that give
      rise to oppositional behavior suggest that different children with ODD may
      require different forms of intervention. The necessity of a transactional
      conceptualization, of achieving a comprehensive understanding of the factors
      underlying the difficulties of individual children with ODD, and of matching
      intervention ingredients to the specific needs of different children and families
      is discussed.

PMID- 11227072
TI  - Callous-unemotional traits and subtypes of conduct disorder.
AB  - There has been growing consensus that children with conduct disorder (CD)
      constitute a very heterogeneous group containing children who vary substantially
      on the development, course, and causes of the disorder. While many have
      recognized the importance of this heterogeneity for developing better causal
      theories and for developing more effective treatments, there has been little
      consensus as to the best way to subtype children with CD. In this paper, we
      review a number of approaches to subtyping, each with some evidence for its
      validity for certain purposes. We focus on two recent approaches that have great
      potential for integrating past subtyping approaches and for advancing causal
      theory. The first approach is the division of children with CD into those with a
      childhood onset to their severe antisocial behavior and those with an adolescent
      onset to their behavior. The second approach is to designate children within the
      childhood-onset group who show callous and unemotional traits, which is analogous
      to adult conceptualizations of psychopathy. Both approaches help designate
      children who many show different causal processes underlying their severe
      aggressive and antisocial behavior, and who may warrant different approaches to
      treatment.

PMID- 11227073
TI  - Interpersonal skills training to reduce aggressive and delinquent behavior:
      limited evidence and the need for an evidence-based system of care.
AB  - The prevention of aggressive and delinquent behavior during childhood and
      adolescence is one of the highest priorities for public health and crime
      prevention. The most common approach to preventing or treating these conduct
      problems has been to provide interpersonal skills training to the affected youth.
      This paper reviews all randomized controlled trials evaluating interpersonal
      skills training programs as an intervention to reduce conduct problems. Research
      shows that such programs have weak empirical support as isolated interventions.
      An alternative evidence-based system of care is described. Such a system would
      include behavioral parent training and behavioral classroom-based interventions
      for young children at risk of developing problems, as well as multisystemic
      family therapy or multidimensional treatment foster care for chronic delinquents.
      Within such a network of services, interpersonal skills training could play an
      important supportive role. Such a system holds the greatest promise for reducing
      the prevalence of aggressive and delinquent behavior in communities.

PMID- 11227075
TI  - Proceedings of the 24th Annual Meeting of the Japanese Society of Sleep Research.
      12-13 June 1999, Hiroshima, Japan.

PMID- 11227074
TI  - Engagement in child and adolescent treatment: the role of parental cognitions and
      attributions.
AB  - Parental engagement in the treatment process is influenced by parents' beliefs
      about the cause of their children's problems, perceptions about their ability to
      handle such problems, and expectations about the ability of therapy to help them.
      This paper examines the role of parental cognitions related to attributions and
      expectations in relation to engagement in child mental health treatment. Reviewed
      studies indicate that parental attributions and expectations influence three
      aspects of treatment: help seeking, engagement and retention, and outcome. This
      paper integrates findings from developmental and clinical research, highlights
      gaps in the literature, presents the beginnings of a model regarding the parental
      attributional process as it relates to engagement in treatment, recommends future
      research directions, and discusses clinical implications.

PMID- 11227076
TI  - [New and recurrent infections].

PMID- 11227077
TI  - 7th International Symposium on Neurobehavioral Methods and Effects in
      Occupational and Environmental Health. 20-23 June 1999. Stockholm, Sweden.
      Abstracts.

PMID- 11227078
TI  - Tuberculosis control in the 21st century. Proceedings of a conference. 21-22
      September 1999, Edinburgh.

PMID- 11227079
TI  - Proceedings of the 32nd Congress of the Japan Epilepsy Society. Yokohama, Japan,
      October 9-10, 1998.

PMID- 11227080
TI  - Proceedings of the XXVIIth Annual Meeting of the Clinical Immunology Working
      Group of the German Society for Immunology. November 1999, Frankfurt/Hoechst.

PMID- 11227081
TI  - Brain-Pituitary-Peripheral Axis. Proceedings of the 5th International Congress of
      Comparative Physiology and Biochemistry. Calgary, Alberta, Canada. August 1999.

PMID- 11227082
TI  - On stability of nonlinear continuous-time neural networks with delays.
AB  - We utilize the Lyapunov function method to analyze stability of continuous
      nonlinear neural networks with delays and obtain some new sufficient conditions
      ensuring the globally asymptotic stability independent of delays. Three main
      conditions imposed on the weighting matrices are established. (i). The spectral
      radius rho(M(-1)(W0 + Wtau)K) < 1. (ii). The row norm M(-1)(W0 + Wtau)K + P(-1)
      ((W0 + Wtau)KM(-1))T P infinity < 2. (iii). mu2(W0) + Wtau2,F < (m/k). These
      three conditions are independent to each other. The delayed Hopfield network,
      Bidirectional associative memory network and cellular neural network are special
      cases of the network model considered in this paper. So we improve some previous
      works of other researchers.

PMID- 11227083
TI  - Management of cervical neoplasia.

PMID- 11227084
TI  - Proceedings of the 4th International Symposium on Population Dynamics of Plant
      Inhabiting Mites. 10-14 May 1999, Kyoto, Japan.

PMID- 11227085
TI  - Looking forward to Reno.

PMID- 11227086
TI  - Certification in Aerospace Physiology.

PMID- 11227087
TI  - Proceedings of the EuroConference: Microdissection and its Downstream Tools.
      Bonn, Germany, 15-17 September 2000.

PMID- 11227088
TI  - 8th KBF Symposium: Complexity in Medicine. 13-15 September 2000. Cologne,
      Germany. Abstracts.

PMID- 11227089
TI  - Choroidal folds and increased intraocular pressure.

PMID- 11227090
TI  - Australasian Division of the International Academy of Pathology Limited 26th
      annual scientific meeting. 2-4 June 2000. Sydney, Australia. Abstracts.

PMID- 11227091
TI  - Epilepsy in the tropics. Proceedings of the 3rd International Congress of
      Tropical Neurology. 30 November-2 December 1998.

PMID- 11227092
TI  - [Oncolytic viruses: sea serpent, virtual reality or real therapeutic virtue].

PMID- 11227093
TI  - Chromosome 13 abnormalities in multiple myeloma are mostly monosomy 13.
AB  - Chromosome 13 abnormalities are frequently   observed in multiple myeloma (MM).
      Several   reports recently demonstrated the strong   prognostic value of these
      abnormalities,   associated with a short survival. Cytogenetic   studies have
      shown that most of these   abnormalities are complete monosomies. In order   to
      define the common minimal deletion, we   analysed a series of 234 patients with
      MM using   fluorescence in situ hybridization (FISH) with a   panel of five
      probes mapping along the whole   chromosome 13. A chromosome 13 abnormality   was
      observed in 98 patients (42%), 90 of whom   (92%) displayed a complete monosomy.
      In seven   of the eight remaining patients presenting partial   deletions, the
      three probes specific for the 13q14   region were deleted. Only one patient (1%) 
      displayed a small deletion of the D13S319 locus.   In conclusion, FISH should be
      used for the   analysis of chromosome 13 abnormalities, using   probes mapping in
      the 13q14 region.

PMID- 11227094
TI  - Renal candidiasis in a 2-month-old infant: treatment of fungus balls with
      streptokinase.

PMID- 11227095
TI  - Granulocyte colony-stimulating factor receptor mutations in a patient with acute
      lymphoblastic leukemia secondary to severe congenital neutropenia.

PMID- 11227097
TI  - Proceedings of the 2nd International Auditory Brainstem Implant Symposium.
      Freiberg, Germany, April 22-24, 1999.

PMID- 11227096
TI  - Proceedings of a meeting on In Vitro Transformation. Cork, Ireland, July 24-25,
      1999.

PMID- 11227098
TI  - Authority figures. Bond-issuing agencies keep an eye on hospitals' financial
      health.

PMID- 11227099
TI  - What is suspected heart failure with preserved left ventricular systolic
      function? Measurement of E:A ratio is both insensitive and non-specific.

PMID- 11227100
TI  - What is suspected heart failure with preserved left ventricular systolic
      function? Clinical suspicion of diastolic heart failure should rely on more than
      symptoms of dyspnoea.

PMID- 11227101
TI  - What is suspected heart failure with preserved left ventricular systolic
      function? Paper does not provide evidence that diastolic dysfunction is a
      misdiagnosis.

PMID- 11227103
TI  - Health professionals need more information on vertical transmission of HIV.

PMID- 11227102
TI  - New drug discovery techniques are not so revolutionary.

PMID- 11227104
TI  - Jung's analysis of Sabina Spielrein and his use of Freud's free association
      method.
AB  - This paper examines Jung's use of Freud's free association method and his own
      association experiments in his analysis of Sabina Spielrein in 1904-1905. Jung's
      gradual rejection of the Freudian free association method is noted. By the time
      of their split in 1913, Jung came to view Freud's method of using associations to
      analyse personal complexes as reductive, limiting and backward-looking. He also
      felt that the Freudian method threatened the analysand by creating confusion and
      a regressive dependency on the analyst. Jung's early approach inclined away from
      personal pain in favour of analysing autonomous, impersonal and collective
      phenomena. The historical question is raised whether Jung's rejection of the use
      of the free associations of the individual analysand might be as fundamental as
      their well-known disagreement about Freud's belief in the central role of
      sexuality in neurosis.

PMID- 11227105
TI  - Sabina Spielrein, a woman psychoanalyst: another picture.

PMID- 11227106
TI  - Sabina Spielrein, Jean Piaget--going their own ways.

PMID- 11227107
TI  - Burgholzli hospital records of Sabina Spielrein.

PMID- 11227108
TI  - The letters of C. G. Jung to Sabina Spielrein.

PMID- 11227109
TI  - Sabina Spielrein: psychoanalytic studies.

PMID- 11227110
TI  - The motor-car--a symbol of male power.

PMID- 11227111
TI  - A dream and a vision of shooting stars.

PMID- 11227112
TI  - Sabina Spielrein. Jung's patient at the Burgholzli.

PMID- 11227114
TI  - The Zurich School of Psychiatry in theory and practice. Sabina Spielrein's
      treatment at the Burgholzli Clinic in Zurich.
AB  - The remarkably caring and privileged treatment of Sabina Spielrein at the
      Burgholzli Hospital 1904/05 (as shown by the records) exemplifies the standards
      and key concepts of the Zurich School of Psychiatry, founded by Auguste Forel and
      represented by the then current director Eugen Bleuler, as well as the specific
      dynamics between Bleuler, his first assistant C. G. Jung, and Spielrein herself.
      Bleuler, in accordance with the trauma theory of hysteria, steadfastly promoted
      the separation from her traumatizing family and supported her scientific
      education. Jung, deeply and emotionally involved, revealed how she had been
      traumatized, but in focusing on her masochistic feelings rather than on the
      victimization, he established a rather conflicted personal relationship with her,
      foreshadowing his later ambivalent attitude to Freud's sexual theory. Thus Sabina
      was discharged with a reasonable psychiatric and scientific education but an
      unreasonable need for personal dependency.

PMID- 11227113
TI  - A document. Jung to Freud 1905: a report on Sabina Spielrein.
AB  - A recently discovered letter, dated September 25, 1905, proves that Jung's first
      attempt to get in contact with Freud had taken place earlier than it had been
      assumed on the basis of their published correspondence. The letter contains a
      brief case history of Sabina Spielrein's illness. It was addressed to Freud and
      handed over to Sabina Spielrein's mother who intended to remove her daughter from
      Jung with whom the girl had fallen in love. However, the letter was never passed
      on to Freud.

PMID- 11227115
TI  - The significance of silence.

PMID- 11227116
TI  - 2000 200-city survey. Operational & clinical EMS trends in large, urban areas.
AB  - The year's survey illustrated ongoing stability with respect to providers and
      operational approaches, and explored relationships that could provide
      opportunities for improvement.  The continued use of hot response to every
      request for service is a high-risk response strategy.  Today's EMD protocol
      systems can enable systems to safely prioritize requests for service.  Response
      time performance reported by measure interval and averaged response time, while
      appearing to follow a rational model for transportation providers, fell short
      with respect to first responder response times which appeared to have no
      correlation with response clock start times.  A possible explanation for this
      difference is the lower percentage of first responder agencies that are subject
      to external response-time performance review.  The medical direction results
      suggest an investment in a full-time medical director could reduce online medical
      control requirements. The use of handheld computing technology could serve as a
      vehicle for building accurate clinical databases, as well as a means to deliver
      DS technology to the patient's bedside.  Use of this technology could also
      improve reimburesment through more accurate reporting.  The future of EMS has
      enormous challenges that must be overcome, especially in light of reduced health
      care insurance reimbursements.  However, these challenges also present an
      opportunity for EMS to reinvent itself.   The capture and analysis of operational
      and clinical data by EMS systems will prove essential to understanding what
      changes can be made to enable them to meet future demands.

PMID- 11227117
TI  - Breathing room.
AB  - Appropriate assessment of the respiratory system begins with a good understanding
      of how this vital system functions. Perform an initial assessment by evaluating
      the patient's general appearance, patency of the airway and work of breathing.
      Vital signs, including pulse ox measurement, must be gathered early. Evaluation
      of the respiratory effort should include the inspection, palpation and
      auscultation. Detection of adventitious breath sounds, such as rhonchi, rales,
      wheezes and pleural friction rub is obviously important. When you've completed a
      good assessment and rendered appropriate treatment, both the patient and the EMT
      can breathe a little easier.

PMID- 11227118
TI  - Seeing red. Progress in pulse oximetry--a powerful tool for EMS providers.
AB  - Ambulance 23 arrives at an extended care facility to transport an 86-year-old
      male. Dispatch assigned the crew to take the patient to his orthopedic surgeon's
      office to have a cast removed from his right leg. Facility staff members report
      the elderly resident has been a little short of breath today, but state he often
      exhibits signs of respiratory distress.

PMID- 11227119
TI  - Cold complications. Assessment & management of hypothermic patients.

PMID- 11227120
TI  - Image of the month. Histoacryl-lipiodol embolization to the lung.

PMID- 11227121
TI  - Oxidant-antioxidant status in acute and chronic renal failure.
AB  - Present study was carried out to evaluate oxidant-antioxidant status and effect
      of hemodialysis in acute and chronic renal failure. Serum MDA levels increased
      while serum SOD found decreased significantly. This study indicates the existence
      and increased production of an oxidizing stress resulting from hemodialysis and
      disturbance in antioxidant enzyme system.

PMID- 11227122
TI  - Comparative study of alkaline phosphatase and prostate specific antigen in
      prostate cancer.
AB  - The study comprised between healthy and benign controls and proven 62 cases of
      prostate cancer at different clinical stages. The mean value of increasing level
      of PSA in group III was found to be highly significant when compared with group
      I. Whereas, the mean value of elevated levels of ALP in stage III and IV from
      group III was found to be highly significant when compared with group I. Though
      the mean value of ALP was increased in stage I and II from group III when
      compared with group I, it was not found highly significant. Hence the elevated
      levels of ALP were significantly correlated with advanced stages of prostate
      cancer. Whereas, increased levels of PSA contribute to the diagnosis of
      potentially increased volume of the prostate cancer.

PMID- 11227123
TI  - Gelastic epilepsy possibly following antirabies vaccine.
AB  - A case of child with gelastic epilepsy following administration of antirabies
      vaccine is presented. No associated structural brain could be identified in the
      patient. Possibility of relationship between antirables vaccine and gelastic
      epilepsy is discussed.

PMID- 11227124
TI  - Compulsive spitting--a culture bound symptom.
AB  - Compulsive Spitting, as a culture bound symptom has not been previously reported
      in the literature. Of 26 cases described, 8 were suffering from schizophrenia
      followed by 5 cases having mania, 4 each with depression and OCD, 3 with tic
      disorder and 2 with seizure disorder. More studies are warranted to study and
      report the culture bound symptoms in india and other countries.

PMID- 11227125
TI  - An unusual post-operative wound infection with Salmonella typhi: case report.
AB  - A 25 year old male student presented with a discharging sinus and swelling over
      right forearm, which on culture yielded S. typhi, sensitive to Ciprofloxacin.
      Predisposing factors were absent but there was a history of surgery for chronic
      osteomyelitis of right ulna and injury with cricket ball at same site. Pus
      obtained during surgery was sterile. Patient responded to oral Ciprofloxacin.
      Soft tissue infections are uncommon manifestation of salmonellosis. This case is
      an unusual presentation of post-operative Salmonella typhi wound infection.

PMID- 11227126
TI  - The cephelosporins.

PMID- 11227127
TI  - AIDS vaccine trial launched.

PMID- 11227128
TI  - Induction of sTNF-R1 and sTNF-R2 by interferon beta-1b in correlation with
      clinical and MRI activity.
AB  - OBJECTIVES: To investigate the influence of interferon (IFN) beta-1b on the serum
      levels of sTNF-R1, sTNF-R2 and TNF-beta in patients with multiple sclerosis (MS)
      in correlation with clinical and MRI activity. MATERIALS AND METHODS: Serum
      samples were obtained every 3 months from 24 patients treated with 8 x 10(6) U of
      IFN beta-lb every other day (treatment group) and from 21 patients without any
      immunomodulatory therapy (control group) over a 15-month observation period. The
      cytokine levels were measured by ELISA. Cranial MRI was performed every 6 months
      to determine the burden of disease of every patient. RESULTS: In the treatment
      group we found an obvious increase of sTNFR1 and sTNF-R2 (P < 0.001) and
      relatively stable serum levels of TNFbeta with no statistical significance (P =
      0.56). In the control group, sTNF-R1 showed a significant decrease (P < 0.001)
      during the same observation period of 15 months. During the 15-month observation
      period, the MRI-responders group had significant larger mean AUC (area under the
      concentration-time curve) values of sTNF-R1 (P = 0.04) and sTNF-R2 (P = 0.01)
      when compared to the group of MRInonresponders. CONCLUSION: The present data
      suggest that IFN beta-1b induces the expression and shedding of TNF-R1 and TNF
      R2. The magnitude of an increase of sTNF-Rs may be a marker for the effectiveness
      of treatment with IFN beta-1b.

PMID- 11227129
TI  - Long-wavelength red light emission from TV and photosensitive siezures.
AB  - PURPOSE: We investigated a role of long-wavelength red light emission from TV in
      the induction of photosensitive seizures by an animated TV program called "Pocket
      Monsters". METHODS: The luminance energy of recorded color bar was measured by a
      spectroradiometer in cathode-ray tubes (CRTs) of photosensitive patients with and
      without seizures on the program (induced patients and photosensitive controls).
      RESULTS: The mean ratio of long-wavelength red light to total visible range was
      significantly higher in the CRTs of induced patients than in the CRTs of
      photosensitive controls. The ratio of luminance energy between at turn-on and at
      60 min after turn-on of the CRTs indicated that luminance energy in long
      wavelength red range from the CRTs of induced patients increased significantly
      after turn-on of CRTs. CONCLUSIONS: High amounts of long-wavelength red light
      emitted from CRTs might play an important role in induction of photosensitive
      seizures in "Pokemon" incident.

PMID- 11227130
TI  - Mutations in the alpha-synuclein gene in Parkinson's disease among Indians.
AB  - OBJECTIVE: To investigate the prevalence of G88C, G209A and any other mutation(s)
      in exons 3 and 4 of the alpha-synuclein gene in Indian patients with Parkinson's
      disease (PD). METHODS: A total of 169 PD patients comprising 18 familial, 3
      juvenile, 48 early onset and 100 sporadic cases were included in this study.
      Genomic DNA was amplified by PCR using primers specific for Exons 3 and 4.
      Mutations at G88C and G209A were screened following restriction enzyme digestion
      of the PCR product. Direct PCR product sequencing of entire exons 3 and 4 was
      carried out for at least one proband each from the 10 familial cases. RESULTS:
      Neither G88C and G209A mutations nor any other mutation in exons 3 and 4 was
      found in the PD patients analysed. CONCLUSION: The G88C and G209A mutations do
      not seem to be the predominant genetic determinant of PD among Indians.

PMID- 11227131
TI  - Donepezil in the treatment of progressive supranuclear palsy.
AB  - OBJECTIVES: To evaluate the effect of 3 month therapy with donepezil, a centrally
      acting cholinesterase inhibitor, on cognitive performances, motor function and
      daily living activities in progressive supranuclear palsy (PSP). MATERIALS AND
      METHODS: Six patients with a diagnosis of PSP were evaluated at baseline and
      after 3 months of treatment with donepezil, 10 mg given at bedtime. Cognitive
      functions, motor symptoms and daily activities were evaluated by means of
      appropriate rating scales. RESULTS: Donepezil was not effective on cognitive
      dysfunction and did not change ratings of daily living. Parkinsonian symptoms
      were unaffected by donepezil treatment. CONCLUSIONS: Cholinergic replacement
      therapy alone is not likely to improve symptoms in a disorder characterized by a
      more widespread impairment of monoaminergic systems. Larger studies may be
      necessary to confirm the lack of effect of donepezil in this disorder.

PMID- 11227132
TI  - Intra vitam lumbar and post mortem ventricular cerebrospinal fluid immunoreactive
      interleukin-6 in Alzheimer's disease patients.
AB  - OBJECTIVES: In view of contradictory findings in previous studies, to examine the
      diagnostic value of interleukin-6 measurements in cerebrospinal fluid (CSF) of
      Alzheimer's disease patients. MATERIAL AND METHODS: Interleukin-6
      immunoreactivity (IL-6-IR) was measured in 169 intra vitam lumbar and 21 post
      mortem ventricular CSF samples of patients with probable and neuropathologically
      confirmed Alzheimer's disease (AD), non-AD dementias (NAD), neurological
      disorders without cognitive impairment (OND) and controls (CON) using a specific
      sandwich enzyme immunoassay. RESULTS: Intra vitam lumbar samples had
      significantly elevated (P < 0.03) IL-6-IR not only in the AD, but also in the NAD
      and OND group compared with controls. AD patients with late onset (> 65 years)
      had slightly (P > 0.05) higher values than patients with early onset (< 65
      years). In post mortem ventricular fluid, differences among groups did not reach
      significance (P > 0.05). CONCLUSION: We conclude that elevations of CSF IL-6-IR
      can not serve as a diagnostic marker of the disease, but, hypothetically, could
      reflect presence or activity of IL-6 mediated immunological phenomena in single
      AD patients.

PMID- 11227133
TI  - Report of a patient with inclusion body myositis and CD8+ chronic lymphocytic
      leukaemia--post-mortem analysis of muscle and brain.
AB  - We report a 73-year-old woman with sporadic inclusion body myositis (s-IBM) and a
      T-cell chronic lymphocytic leukaemia (T-CLL). The s-IBM diagnosis was based on
      clinical symptoms and muscle biopsy showing inflammatory infiltrates and rimmed
      vacuoles with 15 18 nm diameter tubulofilamentous inclusions on ultrastructural
      examination. The inflammatory infiltrates consisted of CD8+ T-lymphocytes and
      macrophages. The diagnosis of a CD8+ T-CLL was based on peripheral blood samples
      and bone marrow aspiration. The postmortem analysis of skeletal muscle showed
      fascicular atrophy, which may support a neurogenic component in s-IBM and the
      analysis of the brain showed only a few diffuse plaques in different cortical
      regions and occasionally neuritic plaques. A pathophysiological analogy between s
      IBM and Alzheimer's has been suggested on the basis of similarities in protein
      accumulation in muscle of s-IBM patients and brain of Alzheimer's patients.
      However, we were unable to detect any changes suggestive of Alzheimer's disease
      in the brain of the s-IBM patient presented here.

PMID- 11227134
TI  - Polymorphonuclear leukocyte integrin pattern in acute ischemic stroke.

PMID- 11227135
TI  - Comparison of MRI, EEG, EPs and ECD-SPECT in Wilson's disease.
AB  - OBJECTIVES: The purpose of this study is to evaluate the efficiency of a few
      methodologies in detecting anatomo-functional brain abnormalities in patients
      with Wilson's disease. MATERIALS AND METHODS: Twenty-three patients with Wilson's
      disease underwent almost simultaneously brain magnetic resonance imaging (MRI),
      computerized electroencephalography (EEG), multimodal evoked potentials (EPs) and
      ECD single photon computerized tomography (SPECT) evaluation. The clinical
      picture was of the neurologic type in 8 patients and of the hepatic type in 15.
      RESULTS: MRI was abnormal in 7 patients with neurological manifestations. The EPs
      proved pathologic in 7 neurologically symptomatic patients and in 4 cases with
      hepatic form. These results agree with those reported in other case studies. The
      EEG records were abnormal only in 3 cases. Nevertheless, the most interesting
      finding of this study is the particular frequency (86%) of diffuse or focal
      decrease of ECD uptake shown by brain SPECT. CONCLUSION: We highlight the use of
      this interesting procedure in the therapeutic monitoring of this disease.

PMID- 11227136
TI  - Personality traits in young patients with Parkinson's disease.
AB  - OBJECTIVES: It has been hypothesized that the dopaminergic deficit of older
      patients with Parkinson's disease (PD) is associated with a reduction in the
      dopamine-dependent personality trait "novelty seeking". It is unknown whether
      this may also be found in younger patients with PD whose dopaminergic deficit is
      considered to be purely motor. MATERIAL AND METHODS: We interviewed 122 patients
      below 51 years of age and 122 age- and sex-matched healthy controls with regard
      to clinical and sociodemographic data. Both groups had to fill out the
      Tridimensional Personality Questionnaire (TPQ) of Cloninger. Neuropsychological
      testing of formal intelligence and depression was also applied. RESULTS: "Novelty
      seeking" was not different between both groups. Patients were more often
      depressed than controls, explaining their difference in "harm avoidance" on the
      TPQ. "Persistence", a sub-scale of the third TPQ dimension "reward dependence",
      was significantly higher in patients. Neither sex, nor age, nor educational
      status were correlated with one of the three personality traits. CONCLUSIONS: The
      higher rate of depression explains our finding of more "harm avoidance" among
      young PD patients. According to a literature review the choice and performance of
      controls is crucial whether personality traits in PD patients may be assessed as
      abnormal.

PMID- 11227137
TI  - The load and distribution of beta-amyloid in brain tissue of patients with
      Alzheimer's disease.
AB  - Recent findings have underlined the significance of beta-amyloid protein (betaA4)
      in the etiology of Alzheimer's disease (AD). In 60 patients with AD, the amount
      of betaA4 deposition, estimated applying immunohistochemical techniques, was
      shown to be significantly influenced by apolipoprotein E (ApoE) genotype
      (epsilon4/epsilon4 > epsilon4/x > x/x), by the age at onset (presenile > senile),
      by the age at death (younger > older patients) and by the duration of the disease
      (long > short). Morphometric analysis revealed that the betaA4 load was highest
      in the superficial layer of the cortex and a significant influence on the
      vertical distribution was seen in females but not in males, in familial but not
      in sporadic cases and in senile but not in presenile cases. Our findings indicate
      that not only the load but also the vertical distribution of betaA4 within cortex
      is influenced by risk factors such as ApoE genotype and gender.

PMID- 11227138
TI  - Neurological disease among women with silicone breast implants in Denmark.
AB  - OBJECTIVES: To investigate the risk of neurological disease among women with
      cosmetic breast implants. MATERIAL AND METHODS: We identified 1,653 women who had
      undergone breast implant surgery at private clinics in Denmark and a comparison
      cohort of 1,736 women who underwent other types of cosmetic surgery at the same
      clinics. Ratios of observed-to-expected numbers of hospitalizations for
      neurological disease in the private implant and comparison cohorts were
      calculated, separately and combined with data from updated public hospital
      cohorts. RESULTS: The occurrence of neurological disease in the private clinic
      implant cohort was comparable to that in the general population. A similar risk
      pattern was observed in the private clinic comparison cohort. When data for these
      private clinic cohorts were combined with updated data for public hospital
      cohorts, excess risks for neurological disorders were seen in both implant and
      comparison cohorts, reaching statistical significance only in the comparison
      cohort. CONCLUSION: Our findings indicate no causal association between silicone
      breast implants and neurological disease.

PMID- 11227140
TI  - [Surgical treatment of carcinoma of the gallbladder: the point].

PMID- 11227139
TI  - Effects of grating spatial orientation on visual evoked potentials and contrast
      sensitivity in multiple sclerosis.
AB  - Previous studies suggest a delay of pattern visual evoked potentials (PVEPs) in
      multiple sclerosis (MS) depending on grating orientation. We examined a group of
      14 patients with definite MS recording PVEPs to vertical and horizontal grating
      and analysing latency and amplitude of P60, N70 and P100 waves. We evaluated
      contrast sensitivity (CS) to dark and bright bars of several spatial frequencies
      (SF). The aim was to evaluate the diagnostic value of evoked responses and CS in
      revealing involvement of cortical structures. PVEPs to 1 degrees cycle/degree
      (c/d) vertical bars were abnormal in 25% for P60, in 32% for N70 and in 36%, for
      P100; in 25%, 36% and 42% respectively at 4 c/d; as regards horizontal bars at 1
      c/d we found alterations of P60, N70 and P100 in 11%, 19% and 27% respectively;
      at 4 c/d in 19%, 27%) and 35%. CS resulted more abnormal for vertical grating,
      with a maximum impairment for 3.7 c/d SF. We may conclude that the use of
      vertical grating in clinical routine is more reliable both for PVEPs and CS
      testing; in addition CS can be abnormal even with normal PVEPs: this could mean
      an early impairment of CS and provide useful indications about a subclinical
      involvement of visual cortex.

PMID- 11227141
TI  - [Is laparoscopic treatment of adhesions a valid approach for postoperative
      abdominal pain?].
AB  - The role of post-operative adhesions in chronic abdominal pain remains
      controversial. The aim of this study was to assess the value of laparoscopic
      treatment of adhesions for chronic post-operative abdominal pain in 32 patients.
      Over a period of 8 years, 32 patients (25 women and 7 men) with a mean age of
      41.5 years (18-69) were hospitalized for chronic abdominal pain of more than 6
      months duration, without an obvious underlying neoplasm or psychiatric disorder.
      They had all undergone at least one previous abdominal operation (mean, 1.9;
      range, 1-5), with a mean follow-up of 28 months (6-82). The mean duration of the
      pain was 18 months (6-65) and in 24 of the 32 cases it was mainly hypogastric.
      Other than the presence of a scar, the clinical examination was completely
      normal. Prior to hospitalization, 163 different laboratory tests, 162
      radiological investigations, including 13 CT scans and 3 MRIs, and 25 endoscopies
      had been performed. A pneumoperitoneum was made by "open laparoscopy" in 23 cases
      and with Verres needle in 9 cases. Eight patients (25%) did not have any
      adhesions, but 6 of them were found to have a gynecological problem
      (endometriosis). In this group, the laparoscopy lasted 34 minutes (15-45) and the
      mean hospital stay was 48 hours. In 24 cases, adhesions were found and selected.
      This was thought to be complete in 22 cases (91.6%). There was a strict
      correlation between the adhesions and the scar in 85% of cases. In 5 cases, the
      adhesions were associated with another intervention. There were no conversions.
      The mean duration of surgery and hospitalization was respectively 56 minutes (32
      120) and 3.2 days. There was no mortality and the morbidity rate was 4.1% (1
      monopolar injury). The average follow-up was 26.7 months: 22 of the 24 patients
      who had freeing of adhesions were evaluated after at least 6 months of follow-up.
      In 10 cases, the pain had completely resolved (45%), in 6 it had decreased (27%)
      and in 6 cases it was unchanged or had even worsened (1 case of endometriosis).
      Laparoscopic exploration for chronic post-operative abdominal pain, after an
      extensive work-up performed after a suitably long delay post-surgery, can be used
      to detect and treat adhesions in 3/4 cases. In the absence of another lesion, the
      pain is lessened in 72% cases. However, if there is another lesion, laparoscopic
      treatment of adhesions is less effective with respect to the pain, but it
      nevertheless can identify an.

PMID- 11227142
TI  - [Clinical study on transient hypocalcemia subsequent to thyroid excision
      interventions].
AB  - The Authors have examined 30 patients post-total thyroidectomy and registered a
      transient decrease of calcemia in 9 and a decrease of PTH in 11. Serum albumin
      and calcitonin were always normal. In all the patients calcemia and PTH returned
      to normal values in 7 days except in 2 patients in whom the values were
      normalized after one month.

PMID- 11227143
TI  - [Intestinal ischemia caused by mesenteric veno-occlusive inflammatory disease:
      description of a clinical case].
AB  - The Authors report a case of small bowel venous ischaemia due to a peculiar form
      of vasculitis called Mesenteric Inflammatory Veno-Occlusive Disease. Such disease
      represents a new anatomopathological entity, with exclusive thrombotic and
      inflammatory infiltration of the mesenteric veins, with no arterial flogistic
      involvement. Clinical manifestation of the diseases is that of the venous
      mesenteric thrombosis in patients in whom the more common forms of systemic
      vasculitis are not recognizable.

PMID- 11227144
TI  - [Clinical and etiopathogenetic evaluation of a rare cause of spontaneous
      pneumoperitoneum and volvulus of the ileum: pneumatosis cystoides intestinalis.
      Report of a case].
AB  - A case of pneumatosis cystoides intestinalis with pneumoperitoneum and volvulus
      complications is reported. After careful examination of the literature,
      etiopathogenic, pathophysiological and clinical features of the disease are
      analyzed by the Authors, also in the light of recent findings. Major diagnostic
      and therapeutic implications are discussed regarding possible complications
      requiring a different therapeutic approach. PCI, a lesion which can be benign,
      primary or secondary in many conditions, may be characterized by the presence of
      spontaneous pneumoperitoneum which only requires a careful, but not aggressive
      therapy, unlike other complications such as volvulus or intestinal occlusion
      which, instead, require timely surgical action. The Authors describing the
      therapy adopted, highlight the positive role of the enteral nutrition (NE) and
      oxygen therapy in the clinical course of the disease.

PMID- 11227145
TI  - [A case of extraskeletal Ewing's sarcoma of the thoracic wall].
AB  - The Authors report a case of extraskeletal Ewing's sarcoma of thoracic wall in a
      15-year-old sport-man, who complained about pain in the left upper extremity. The
      diagnosis was performed by radiology (ultrasound study, TC, RM) and pre-operative
      needle-aspiration biopsy. The patient was treated by neoadjuvant chemotherapy,
      wide surgical resection and, then, radiotherapy. Neither local recurrence nor
      metastases have developed for 8 months.

PMID- 11227146
TI  - [Phyllodes tumor of the breast. Personal contribution of 21 cases].
AB  - The study is based on the observation of 21 cases of phyllodes tumour of the
      breast. The mean age of patients was 43 years (range 18-60 years). In all the
      cases the tumour was monolateral, more common in the right breast (66.7% vs.
      33.3%) and in external quadrants. Clinical features and diagnostic investigations
      were able to make a preoperative diagnosis in 6 out of 21 cases, while frozen
      sections and histological examination allowed to diagnose in the others. FNAB was
      not performed in any case. In this way 18 benign and 3 "borderline" tumours were
      discovered. No malignant lesion was observed. Local recurrence rate was 14.6%.
      Local recurrence was not associated with age of patients, tumor size and
      histological type. In neither case axillary nodal involvement was found. The
      study and the review of the literature suggest that wide local excision is the
      treatment of choice and adjuvant therapies have no place in the routine
      management of phyllodes tumours.

PMID- 11227147
TI  - [Azygos lobe and spontaneous pneumothorax].
AB  - The association azygos lobe-pneumothorax is a very rare event described in
      literature. The Authors report a case observed. The surgical procedure performed
      by traditional thoracotomy, was carried out with the section of the azygos and
      the resection of small blebs in pulmonary apex. Finally, emphasized possible
      different pathogenetic mechanisms.

PMID- 11227148
TI  - [Monomorphic adenomas of the parotid gland: description of 3 clinical cases].
AB  - Three cases of monomorphic adenomas (two oncocytic adenomas and one basal cell
      adenoma) of the parotid gland are reported. The diagnosis is based on echography
      with fine needle biopsy and cervical computerized tomography. Because of the high
      percentages of multicentricity, the therapy of choice is superficial
      parotidectomy when the lesion is in the pre-neural lobe of the gland, or total
      parotidectomy in case of a deep mass.

PMID- 11227149
TI  - [Layered and mass sutures in the closure of median laparotomies].
AB  - A retrospective comparison of 2830 patients with midline abdominal incision
      closures was made. Dehiscences, infections, hernias were compared examining
      continuous mass closures (group A) versus interrupted mass closures (group B) and
      interrupted layered sutures (group C). The three groups were well matched for
      known risk factors for each of the above complications. Mass closures produced a
      significant higher number of infections (p = 0.0006) and hernias (p = 0.0001).
      There was no significant difference in the rate of dehiscences in the three
      suture groups (p = 0.07). A significant correlation was found in all three groups
      between the incidence of infections and that of outcoming incisional hernias. In
      the current study layered closure of the of the midline abdominal wounds yielded
      better results when compared with both running mass and interrupted mass
      closures. The knowledge of these findings might help when choosing the procedure
      to close a midline abdominal incision.

PMID- 11227150
TI  - [Therapeutic strategies in differentiated cancer of the thyroid: total
      thyroidectomy].
AB  - Differentiated thyroid cancer is peculiar for its prognosis often excellent. The
      Authors report their experience about 78 patients affected with differentiated
      thyroid carcinoma, operated between 1976-1999 at the Institute of Surgical
      Pathology and Surgical Clinic of Cagliari University. 70 (89.7%) patients
      underwent total thyroidectomy, 6 (7.5%) subtotal thyroidectomy and 2 (2.5%)
      thyroid lobectomy. In 11 patients total thyroidectomy was performed in two times
      within 60 days after initial lobectomy. Tumor was found in 2 (18%) of 11 of the
      reoperations. Lymphadenectomy was performed only in presence of cervical lymph
      nodal metastases. Following 70 total thyroidectomy the incidence of recurrent
      nerve palsy was 4.2% and permanent hypoparathyroidism 11.4%. 79% patients
      received adjuvant postoperative radioiodine therapy to ablate residual
      functioning tissue or distant suspected metastases. After a mean follow up period
      of 5.8 years, recurrences developed in 10.2%. Any local recurrences, 5 (6.4%)
      cervical nodal recurrences, 3 (3.8%) distant metastases were encountered. Two
      (2.5%) of the three patients with recurrence distant metastases died from thyroid
      carcinoma. The Authors identify total thyroidectomy as the minimal procedure.
      Surgical management of the cervical nodes is recommended only in the presence of
      metastatic lymph-nodes. Post surgical ablation with I131 of microscopic remnants
      optimize detection and treatment of the recurrence and distant metastases.

PMID- 11227151
TI  - [Imaging of vitreoretinal adhesions in the partner eye of patients with
      penetrating macular foramina in optical coherence tomography].
AB  - BACKGROUND: Vitreoretinal adhesions play a crucial role in the development of a
      macular hole. To visualize vitreoretinal adhesion we used optical coherence
      tomography to investigate fellow eyes of patients with macular holes. METHODS: In
      a prospective study we scanned the retina in 188 patients with a macular hole
      stage III or IV (Gass classification). The foveal shape and vitreous were
      classified into grades. RESULTS: Of the 188 patients 45% showed no vitreous
      reflex, 45% a partial vitreous detachment with foveolar adhesions, and 10% a
      vitreous detachment with complete separation from the fovea. While eyes with
      normal foveolar shape displayed partial vitreous detachment in 33%, this figure
      rose to 66% in eyes with a macular hole stage I. CONCLUSION: Diffuse thickening
      of the fovea is followed by an intraretinal split and formation of a cyst. The
      shape of the foveolar adhesion suggests that continuing anteroposterior vitreal
      traction leads to a retinal break and formation of a full-thickness macular hole.

PMID- 11227152
TI  - [Correction of myopia and astigmatism using topography-assisted laser in situ
      keratomileusis (TopoLink LASIK)].
AB  - PATIENTS AND METHODS: We treated 114 patients (eyes) with myopia of -1 to 6 D and
      astigmatism of 0 to -4 D (group 1), and 89 patients (eyes) with myopia of -6.1 to
      -12 D and astigmatism of 0 to -4 D (group 2). All treatments were calculated on
      the basis of corneal topography measured with the Orbscan II system. The Keracor
      217 excimer laser and the Hansatome microkeratome were used. RESULTS: At 3
      months, 51 patients in the low myopia group and 40 patients in the high myopia
      group were available for examination. In the low (high) myopia group, 96.1%
      (75.0%) were within +/- 0.50 D of emmetropia, and uncorrected visual acuity was
      20/20 or better in 82.4% (62.5%), 20/25 or better in 98.0% (70.0%), and 20/40 or
      better in 100% (95.0%). A loss of two or more lines of spectacle-corrected visual
      acuity occurred in 3.9% of the low and 5.0% of the high myopia group. In low
      myopia, spectacle-corrected visual acuity was 20/12.5 or better in 5.9%
      preoperatively and in 13.7% at three months and 20/15 or better in 37.3% and
      47.1%, respectively (P = 0.0002 and P = 0.01). CONCLUSIONS: LASIK based on
      corneal topography showed very high efficacy in low and moderate myopia with
      astigmatism, and maximal visual acuity could even be improved in some cases.
      There was somewhat less precision in high myopia with astigmatism.

PMID- 11227153
TI  - [Development of endothelial cell number in the host corneal endothelium. Status
      after block excision and eccentric corneal scleroplasty].
AB  - PURPOSE: Block excision of anterior uveal tumors and cystic epithelial ingrowth
      to the anterior chamber is a curative treatment for morphological rehabilitation
      of the globe. This study quantified the course of the host corneal endothelium
      after this peripheral corneoscleral graft. PATIENTS AND METHODS: This
      retrospective cross-sectional study examined 53 specular microscopic photographs
      of the central host cornea in 30 patients. The diameter of the block excision was
      8.5 +/- 1.9 mm (6.0-11.0 mm). Follow-up after surgery averaged 37.9 +/- 47.6
      months (1-216). RESULTS: The corneal endothelial cell count decreased with the
      duration of follow-up after block excision. The cell count was not related to
      indication for surgery or to diameter of block excision. Mean visual acuity was
      16/20 before block excision and 6/20 at the end of follow-up. CONCLUSION: There
      is a significant loss of endothelial cells of the host after block excision,
      requiring a second central penetrating keratoplasty in some patients. Loss of
      endothelial cells may be due to the surgical trauma, chronic immunological
      reaction against the donor endothelium, or migration of the host endothelial
      cells onto the corneoscleral graft.

PMID- 11227154
TI  - [CO2 and erbium YAG laser in eyelid surgery. A comparison].
AB  - BACKGROUND: Lasers are finding increasing use in cosmetic and reconstructive
      plastic surgery. We compared the erbium-YAG laser and the CO2 laser to
      conventional eyelid surgery with a scalpel. MATERIAL AND METHODS: We operated on
      58 patients using the erbium-YAG laser and on 32 using the CO2 laser. Surgeries
      were benign tumor excisions and removal, xanthelasma removal, lower and upper
      eyelid blepharoplasties, and skin resurfacing in the area of the lower eyelid.
      RESULTS: Wound healing with the CO2 laser was significantly slower because of its
      larger thermal necrosis zone, but the hemostasis with the CO2 laser makes removal
      of deeper lesions easier. Advantages are the wide application spectrum for
      incisional and ablative surgery. The erbium-YAG laser is an excellent for
      ablating superficial benign lesions, including that in the area of the lid margin
      and close to the lacrimal puncta without scars. SUMMARY: The application
      spectrums of the erbium-YAG and CO2 lasers complement one another. The erbium-YAG
      laser is superior for esthetic skin resurfacing and ablation of superficial
      lesions, and the CO2 laser allows hemorrhage-free noncontact incisional surgery.

PMID- 11227155
TI  - [Site of a polyurethane stent in dacryocystography. Is postoperative success
      hereby predictable?].
AB  - BACKGROUND: Despite new methods for treating complete stenosis of the
      nasolacrimal duct dacryocystorhinostomy remains the standard operation.
      Implanting a nasolacrimal polyurethane stent through the nasolacrimal duct to
      preserve the natural lacrimal pathway seems to offer alternative procedure with
      similar success rate and without skin incision and general anesthesia. We
      examined whether an anatomically correct position increases its success rates.
      METHODS: This prospective study included 40 patients (mean age 57 years). The
      polyurethane stent was implanted during dacryocystography, and its position was
      checked at follow-up visits after 6 months. In the event of an additional
      canalicular stenosis a 45-mm-long stent was implanted, in the other patients a 35
      mm-long stent. RESULTS: A dacryocystographically correct position was found in
      only 21 of 40 patients; in the other 19 the stent did not enter the nose under
      the inferior concha. However, there was no correlation between correct position
      under the inferior concha and success rate. In 8 of the 40 patients the stent was
      not patent. CONCLUSION: The postoperative success rate cannot be predicted by the
      radiographic position along the ductus nasolacrimalis.

PMID- 11227156
TI  - [Reading speed in movement in the peripheral visual field].
AB  - BACKGROUND: Moving and distracting stimuli often occur in the peripheral visual
      field during visual tasks in daily life. Do they influence reading performance?
      METHOD: In 30 normal subjects with a normal visual acuity we investigated eye
      movements by electronystagmography (ENG) during silent reading of a standardized
      text. The 17 degrees-wide text was presented at a distance of 1 m, ENG was
      recorded bitemporally. Blinks were monitored via vertical ENG electrodes. For
      surrounding stimulation we presented a bar stimulus moving at 30 degrees/s. Three
      experimental conditions were compared: [1] no peripheral motion, [2] peripheral
      motion to the right, and [3] peripheral motion to the left. We quantitatively
      analyzed reading speed and blink frequency. RESULTS: Reading speed and blink
      frequency was nearly identical in the three experimental conditions, they
      differed by 1-8%. CONCLUSIONS: Although the full periphery was stimulated, and
      the moving stimulus was noticed by our subjects, reading was not affected by
      surrounding optokinetic stimulation. Attentive reading does not appear to be
      affected by visual motion in the periphery.

PMID- 11227157
TI  - [Leber optic neuropathy with clinical improvement].
AB  - BACKGROUND: Spontaneous recovery in Leber's hereditary optic neuropathy is rare.
      Does the clinical course of Leber's hereditary optic neuropathy (LHON) differ
      between patients with and without spontaneous recovery? MATERIALS AND METHODS: We
      compared the clinical and molecular genetic characteristics of 12 visually
      symptomatic patients having the classical clinical course of LHON who recovered
      spontaneously with those of 60 who did not. RESULTS: Classical fundus findings
      and typical visual field defects were comparable in the two groups; vision
      improved within 18 months in all cases. The worst visual acuity during the acute
      stage of LHON was 0.03 in the recovery group. Patients with the 3460 and
      especially the 14484 mutation had a better chance of recovery. No patient with
      the 11778 mutation who recovered had secondary mutations. Among patients who
      recovered women were underrepresented and heteroplasmy was more common. Some
      families showed a raised rate of clinically affected members with recovery.
      CONCLUSIONS: The clinical picture of LHON remains the same regardless of whether
      the patient recovers spontaneously. A higher rate of spontaneous recovery
      characterizes some families. Spontaneous recovery is rare in women. Heteroplasmy
      is frequent in patients with recovery. Our results show a better clinical course
      of LHON in patients with the 11778 mutation without secondary mutations.
      Prognosis is better if the peripapillary microangiopathy is seen for a relatively
      long period, and there is only partial optic atrophy.

PMID- 11227158
TI  - [Analysis of the dynamics of the ciliary muscle during accommodation].
AB  - BACKGROUND: The magnitude of anterioaxial shift of the human ciliary muscle
      during accommodation and its ceasing of ciliary function with advanced age are
      still unknown. PATIENTS AND METHODS: A total 105 patients (aged 10-91 years) were
      examined by high-resolution ultrasound biomicroscopy during disaccommodation and
      voluntary accommodation. Accommodative changes in the total area of the ciliary
      muscle and in the outer contour were quantified with a specially developed
      software program for automatic contour determination. RESULTS: A significant
      anterior shift independent of age was observed in the total area of the ciliary
      muscle and defined points on the outer contour of the muscle in the range of 56
      121 microns, while the inward displacement was less obvious. A decrease in the
      magnitude of configurational changes during accommodation was observed with age.
      CONCLUSION: The new software program could be useful in further investigations of
      the accommodative process and evaluation of the potential causes of presbyopia.

PMID- 11227159
TI  - [Ophthalmodynamometry. A reliable procedure for noninvasive determination of
      intracranial pressure].
AB  - BACKGROUND: Central vein pressure depends on intracranial pressure (ICP).
      Baurmann in 1925 therefore recommended measuring central vein pressure to
      determine ICP, but the accuracy of this method has not yet been verified. To test
      the method we measured venous outflow pressure (VOP) by noninvasive
      ophthalmodynamometry (ODM). METHODS AND MATERIALS: We studied 31 patients with
      suspected increased ICP. ICP was recorded continuously for a minimum of 24 h by
      intraventricular catheters, and ODM was performed during ICP measurement. The
      findings were compared with the results of conventional invasive ICP measurement.
      RESULTS: Pressure in the central retinal vein was highly correlated with ICP.
      CONCLUSION: Measuring VOP by ODM seems to be a reliable method for noninvasive
      recording of ICP. It is a useful screening test in all cases of presumed ICP
      elevation.

PMID- 11227160
TI  - [Cyclosporin A therapy in severe anterior scleritis. 5 severe courses without
      verification of associated systemic disease treated with cyclosporin A].
AB  - BACKGROUND: Patients with severe scleritis who do not respond to high-dose
      corticosteroid therapy, or who require a daily corticosteroid maintenance dose
      higher than 30 mg prednisone should be treated by other immunosuppressants.
      PATIENTS AND METHODS: In five patients with various types of severe anterior
      scleritis a long-term high-dose steroid treatment failed to control scleral
      inflammation. They therefore received cyclosporin (CsA). Follow-up was 16-26
      months. RESULTS: Scleral inflammation and ocular complications were controlled in
      all patients by a regimen of systemic CsA combined with a low maintenance steroid
      dose below the Cushing threshold. We observed no side effects under CsA serum
      levels of 120-150 ng/ml. In only one patient was scleral inflammation totally and
      lastingly eliminated. CONCLUSIONS: Systemic CsA therapy is of definite
      therapeutic value in the symptomatic management of steroid refractory severe
      anterior scleritis without associated systemic disease. Complete healing,
      however, is achieved only in a minority of cases.

PMID- 11227161
TI  - [Endoscopically controlled surgery with the micro-drill and intubation of the
      lacrimal ducts].
AB  - PURPOSE: Operative procedures to manage lacrimal outflow obstruction were made
      traditionally without endoscopic assistance. For dacryoendoscopy we previously
      used a 0.5-mm endoscope with a special wash cannula. We now use the
      microendoscope Vitroptic T for dacryoendoscopy and for endoscopically controlled
      surgery with a microdrill. METHODS: In an attempt to perform microinvasive
      lacrimal surgery we use a 1.1-mm endoscope (Vitroptik T) with a wash cannula, a
      channel for the microoptic and a channel for a microdrill. We report on our
      initial experiences and on the results of eight patients with stenosis of the
      lacrimal outflow system who were treated with an endoscopic microdrill and
      silicone tubing. One patient had lacrimal stenosis after external
      dacryocystorhinostomy (DCR), and seven patients showed punctual stenosis in the
      nasolacrimal duct. RESULTS: Using the dacryoendoscope (Vitroptic T) we were able
      to visualize pathologic changes of the lacrimal outflow system. Intraoperative
      situations during dacryoendoscopy are demonstrated. The Vitroptic T allows
      dacryoendoscopy and endoscopically controlled surgery of the lacrimal drainage
      system. Three months after surgery in six patients (75%) the lacrimal outflow
      system was patent with the silicone tube in place, and these patients had no
      epiphora. The patient with re-stenosis after external DCR showed patency.
      CONCLUSIONS: Dacryoendoscopy and endoscopic controlled surgery of the lacrimal
      drainage system enables atraumatic and minimally invasive surgery. The Vitroptik
      T with the microdrill allows endoscopically controlled microsurgery. Possible
      indications for the microdrill are punctual stenosis and re-stenosis after
      external DCR.

PMID- 11227162
TI  - [Blindness caused by an airbag in a minor accident].
AB  - PURPOSE: Installation of airbags has reduced the rate of fatal injuries in severe
      automobile accidents. We report, however, severe ocular injuries in a minor
      accident as the result of an airbag. CASE REPORT: A front passenger suffered a
      blunt ocular trauma of her right eye during a collision. The approaching speed
      was about 31 km/h. The maximum change of velocity in direction of the impact was
      19 km/h. Color traces were found on the upper rim of the airbag, apparently from
      the patient's eye shadow. RESULTS: In the emergency room, visual acuity was
      reduced to light perception. There was endothelial contusion, traumatic
      mydriasis, and lens subluxation. A sclopetarian retinopathy developed with a
      chorioretinal scar. Eight months after the accident visual acuity remained at
      light projection only. CONCLUSIONS: The eye injuries had very probably been
      caused by the deploying airbag. Improvements are a better geometry of deployment
      (e.g., tethered airbags), release at higher impacts only, and "intelligent
      systems" with additional sensors to avoid potentially hazardous airbag inflation
      in minor accidents.

PMID- 11227163
TI  - [Cyanoacrylate injuries of the eye].
AB  - BACKGROUND: Cyanoacrylates are contained in nail glues, instant glues, and tissue
      adhesives such as Histoacryl. Cyanoacrylates may inadvertently contaminate the
      conjunctival sac and cause massive loss of visual function and serious discomfort
      to the patient. PATIENTS: Over a 10-year period five patients with a
      cyanoacrylate lesion of the ocular surface have been observed. Four were injured
      by instant glue and one by Histoacryl. Therapy included moderate rinsing. In the
      most severely affected patient parts of the glue were removed mechanically;
      spontaneous rejection of the glue was awaited in the other four. After the glue
      had been rejected, four patients showed corneal erosion which healed without
      problems. Visual function returned to normal in all patients, and there was no
      persistent tissue damage. CONCLUSIONS: Cyanoacrylates exert no substantial
      thermal, chemical, or toxic effects on the ocular surface when inadvertently
      entering the conjunctival sac. Cyanoacrylate trauma therefore has a very
      favorable prognosis. The conservative approach of awaiting spontaneous glue
      rejection is appropriate.

PMID- 11227165
TI  - [Online literature search].
AB  - The internet offers charge-free access to electronic online databases and thus
      has revolutionized the handling of information. Today's challenge is the rational
      management of the large amount of attainable data. This overview presents the
      various databases--particularly databases for online Medline search--and basic
      knowledge for effective and successful search strategies. There are numerous
      important advantages of online access to literature databases: availability at
      any time and any place in the world, easy handling due to the user-friendly
      surface of the World Wide Web, capability of linking directly to the private
      database. Clinicians, scientists, and ophthalmologists in private practice can
      equally profit from the advantages of fast, easy, and charge-free online-search
      in medical literature databases. Literature search should thus be an important
      tool to obtain the latest scientific knowledge for every physician.

PMID- 11227164
TI  - [Bilateral simultaneous LASIK. Pro and contra].
AB  - Until recently simultaneous bilateral laser in situ keratomileusis (LASIK) was
      regarded as contraindicated in Germany. However, the procedure was sporadically
      performed, because it offers patient comfort and is more cost effective than
      sequential LASIK. Even though the complication rate is below the calculated rate
      of 0.01%, bilateral complications may have catastrophic effects on the patient.
      In addition, there is the theoretical disadvantage that the results from the
      first eye cannot be used for the second eye. However, this effect has yet to be
      clinically proven.

PMID- 11227166
TI  - [Erythematous eyelid swelling after dacryocystography. Perforation of the
      efferent lacrimal ducts in dacryocystography with contrast medium extravasation].

PMID- 11227167
TI  - [Increased glare and distorted vision. Sympathetic ophthalmia after glaucoma
      surgery with uveal trauma].

PMID- 11227168
TI  - [Electrophysiological diagnosis in ophthalmology].

PMID- 11227169
TI  - [Reduced tear secretion after craniocerebral trauma. Keratoconjunctivitis sicca
      after skull base fracture by damage to the parasympathetic innervation lacrimal
      gland].

PMID- 11227170
TI  - Sugar as a slimming agent?

PMID- 11227171
TI  - [Essential phospholipids in the treatment of hepatic encephalopathy].
AB  - THE AIM: To evaluate the effect of treatment with intravenous essentiale
      phospholipids in patients with liver cirrhosis and hepatic encephalopathy grade
      III-IV. PATIENTS AND METHODS: 12 patients with hepatic encephalopathy grade III
      IV due to decompensated liver cirrhosis, age 35-67 years, were randomized to two
      groups: Essentiale 2.0 g i.v. daily was given to 6 patients in combination with
      standard therapy for 2 weeks; 6 patients had only standard therapy. The patients
      were followed up for 90 days. The diagnosis of hepatic encephalopathy was based
      on clinical examination, psychometrical tests and neurophysiological examination
      EEG and evoked potentials. RESULTS: Mean survival in the group treated with
      Essentiale i.v. was 50.3 days in comparison to 34.7 days in control group. P300
      latencies improved significantly in the Essentiale group in comparison to control
      group (427.5 ms before vs 366.3 ms after treatment period in the treated group;
      346.6 ms before vs 347.5 ms after treatment period in controls). Ammonia level
      decreased form 95 mumol/l. 5 to 49.7 mumol/l in the treated group, while in
      controls remained unchanged (46.5 mumol/l before vs 53.5 mumol/l after treatment
      period). No adverse reactions were observed during the treatment with Essentiale
      i.v. CONCLUSION: Administration of Essentiale i.v. is a safe treatment of
      advanced liver disease. In the group of patients treated with Essentiale i.v. was
      observed prolonged survival, as an improvement of hepatic encephalopathy in
      comparison to control group.

PMID- 11227172
TI  - [Thallium scintigraphy of the myocardium in evaluation of patients with insulin
      resistance syndrome and microvascular angina pectoris].
AB  - Insulin resistance syndrom (IR) is often associated with the syndrome of
      microvascular angina pectoris (MVAP) or with coronary artery disease (CAD). The
      authors quantified distribution and washout of 201Tl in heart (C), lungs (L) and
      liver (H) to evaluate the results 201Tl stress (s) and redistribution SPECT in 50
      patients. They compared 2 groups of patients with laboratory verified IR (MVAP
      and CAD) and control group (CG) of patients with normal coronarography without
      any symptoms of IR. In Patients with IR and MVAP were found significantly more
      frequent local perfusion abnormalities then in CG. The index sL/C calculated by
      ROI analysis is significantly lower in controls, then in CAD. The index sC/H is
      lower in patients with IR (MVAP significantly) then in CG. The washout of 201Tl
      in CAD myocardium decreased and in MVAP liver increased. 201thalium scintigraphy
      is useful for separation of patients with MVAP and local perfusion abnormalities.
      This findings had probably prognostic value in patients with IR.

PMID- 11227173
TI  - [Gastric emptying in diabetics].
AB  - The authors evaluate gastric emptying in diabetic patients and follow up selected
      factors which may influence it. METHOD: In a group of 25 type 1 diabetics
      selected at random (12 women and 13 men), mean age 40.5 years +/- 11.6 SD (range
      21 to 57 years) with a duration of diabetes of 17.8 +/- 7.9 years (minimum 4,
      maximum 35 years) with a mean value of glycosylated haemoglobin of 8.71% +/- 1.82
      (minimum 7.2, maximum 12.2%) the authors assessed: the time of gastric emptying
      by scintigraphic follow up of the progress of solid food (rice labelled with
      99mTc). 2. The correlation of gastric emptying and time factors (age, duration of
      diabetes) and metabolic factors (blood sugar level, glycosylated haemoglobin). 3.
      Relations of impaired gastric emptying and the presence of gastrointestinal
      symptoms. RESULTS: Only 9 patients had normal gastric emptying (36%). In 16
      patients (64%) the time was pathologically altered, incl. 5 (20%) where the
      period was reduced, while in 11 (44%) the time was prolonged. After classifying
      the diabetics into three groups according to the period of gastric emptying in
      minutes (group I < 40, group II 40-90, group III > 90) by means of the
      statistical method ANOVA a significant correlation was found between the time of
      gastric emptying and age (p < 0.036) and the duration of diabetes (p < 0.0044).
      No significant relationship was found between metabolic parameters (blood glucose
      level, glycosylated haemoglobin) and the time of gastric emptying. The authors
      did not find any significant relationship between impaired gastric emptying and
      subjective symptoms. CONCLUSION: Impaired gastric emptying is frequently
      encountered in diabetics. In the authors group there was only a correlation
      between the time of gastric emptying and age and the duration of diabetes. The
      authors did not find a relationship with the blood glucose level or glycosylated
      haemoglobin. Impaired gastric emptying was not correlated with subjective
      gastrointestinal symptoms.

PMID- 11227174
TI  - [The bioartificial liver--an alternative in the treatment of acute liver
      failure].
AB  - One of the therapeutic approaches in acute liver failure is the use of an
      artificial system replacing hepatic function--bioartificial liver. Its
      application is the most perspective in fulminant liver failure during preparation
      for transplantation of the liver (so-called bridge to transplantation) or in case
      of a non-functioning hepatic graft, and to reduce the mortality and morbidity of
      patients with acute liver failure where transplantation is not indicated or where
      a suitable graft was not found. The authors discuss briefly the construction of
      these systems, analyze different indications of treatment and its results,
      obscure questions and perspectives of further development.

PMID- 11227176
TI  - [Can we foresee the end of the alphabet in viral hepatitis?].
AB  - There is a number of viruses which may cause acute or chronic liver damage. Only
      some of them belong into the group of hepatotropic viruses and only the latter
      are the cause of acute or chronic viral hepatitis. So far we know seven
      hepatotropic viruses. The virus of hepatitis A (HAV), virus of hepatitis B (HBV),
      virus of hepatitis C (HCV), virus of hepatitis D (HDV), virus of hepatitis E
      (HEV), virus of hepatitis G (HGV) and Transfusion-Transmitted-Virus (TTV). For
      HAV and HEV orofaecal transmission is typical, the others are transmitted by the
      parenteral route. All cause acute hepatitis. Only HAV and HEV infections develop
      into the chronic stage. The decisive finding for the dynamic development of the
      problem of viral hepatitis was the discovery of the Australian antigen (Au
      antigen) by B. Blumberg in 1965. The discovery made it possible to recognize
      viral hepatitis B and by the application of new biotechnologies the genes of
      other viruses were detected. Some of them were not visualized so far. A great
      advance was alpha interferon and lamivudine treatment in patients with chronic
      hepatitis B and alpha interferon treatment along with ribavirine in chronic
      hepatitis C.

PMID- 11227175
TI  - [Treatment of Hodgkin's disease using the German Study Group protocol. Personal
      experience and results].
AB  - The article present an evaluation (02/1999) of the study of primary treatment of
      Hodgkin's disease (HD) according to the third generation of the German Hodgkin's
      Disease Study Group (GHSG), and our experience with this treatment strategy. HD7
      study of early stages HD showed better results (fewer relapses) for combined
      chemo and radiotherapy than for radiotherapy alone (2x ABVD + extended field
      radiotherapy compared to extended field radiotherapy alone). HD8 study of
      intermediate stage HD did not show any difference between chemotherapy 2x (COPP +
      ABVD) combined with radiotherapy extended field, or involved field. Due to the
      long-term consequences (especially secondary neoplasm), in the current (fourth)
      generation protocol extended field radiotherapy in early and intermediate stage
      HD has been replaced by a combination of lesser toxic chemotherapy and involved
      field radiotherapy. HD9 study of advanced HD. The standard treatment at present
      of COPP/ABVD (A) was compared with the new chemotherapeutic regimen, BEACOPP
      baseline (B) and escalated (C). The first evaluation of this study (1996) showed
      better results in the case of BEACOPP. The latest evaluation showed significantly
      better results for the escalated version. This is best illustrated by the low
      percentage of disease progression (C 2%, B 8%, A 12%, p < 0.05). Therefore, DHSG
      is considered to be the new standard for treatment of advanced stage HD. OUR
      RESULTS: Between 1995-1998, 54 patients with primary HD were treated at the FN
      Kralovake Vinohrady, Prague according to the third generation GHSG protocol. Of
      these, 5 patients (9%) according to HD7, 14 (26%) according to HD8 and 35
      patients (65%) according to HD9. Our results correspond to those of the whole
      GHSG, but they can not be statistically evaluated because of the small number of
      patients involved.

PMID- 11227177
TI  - [Characteristics of still unknown hepatotropic viruses and a clinical picture of
      the disease].
AB  - So far seven hepatotropic viruses were identified. They are described by letters
      A,B,C,D,E, G and TTV. The virus of hepatitis F is so far speculative. Virus of
      hepatitis A and E are transmitted by the orofaecal route and cause only acute
      hepatitis. The remaining hepatotropic viruses are transmitted by the parenteral
      route and have a longer incubation period than viruses A and E. The infection
      with the virus of hepatitis B develops into the chronic stage in about 10% and
      that of virus C in 50-90%. At least one third of chronic carriers of the virus of
      hepatitis B or C develop within 10-20 years liver cirrhosis or hepatocellular
      carcinoma. The objective of therapeutic regimes is eradication of the viruses or
      at least arrest or retarding of the activity of the disease. Corticoids are not
      used. The basis of therapeutic regimes is interferon alpha or lamivudine in
      hepatitis B and interferon alpha with ribavirine in hepatitis C. There is a
      permanent therapeutic response only in cca 40-50%. Active immunisation is
      possible against virus of hepatitis A and B. The virus of hepatitis D is a false
      virus, i.e. a so-called virold, and the cause is a super- or co-infection with
      the virus of hepatitis B. In this country it is practically not encountered,
      similarly as the virus of hepatitis E. The assembled findings on virus of
      hepatitis G are not applied so far very much in practice.

PMID- 11227178
TI  - [Corticosteroids in the treatment of rheumatic diseases].
AB  - The author describes the use of corticosteroids in the treatment of rheumatic
      diseases. He mentions different indications, incl. controversial vones, the
      problem of dosage and undesirable effects of treatment.

PMID- 11227179
TI  - [Topical therapy with corticosteroids in rheumatology].
AB  - The author summarized when and how to use steroid-injection therapy. He mentions
      indications, contraindications, complications and the controversial uses of the
      local treatment.

PMID- 11227180
TI  - [Effect of pancreatic substitutes on fecal and serum elastase and on pain in
      patients with chronic pancreatitis].
AB  - Views on the existence of a negative feedback between pancreatic secretion and
      intraduodenal of proteases in humans are controversial. The objective of the
      study was to find out whether enzyme substitution will have an impact on
      pancreatic enzyme secretion and pain in chronic pancreatitis. The preparation
      Panzytrate 2500 (2 x 3 capsules/day containing 1250 units of proteases per
      capsule) was administered for a 4-week period. In 18 patients with chronic
      pancreatitis (7 with the severe and 11 with the medium severe and mild form of
      pancreatitis) the faecal and serum pancreatic elastase was assessed one day
      before and one day after enzyme substitution therapy. A significant reduction of
      the faecal elastase concentration (p = 0.03) and serum elastase (p = 0.00375) was
      recorded in patients with mild and medium severe CP. The values of faecal and
      serum pancreatic elastase 1 were insignificantly reduced also in patients with
      severe chronic pancreatitis. Pain relief was statistically significant already
      after two weeks' administration of enzyme substitution therapy (p = 0.0233) and
      after four weeks' treatment (p = 0.00766). The results support the importance of
      the negative feedback on regulation of pancreatic secretion and the positive
      effect of substitution therapy on pain in chronic pancreatitis.

PMID- 11227181
TI  - [Effect of high-dose chemotherapy in patients with relapsing or resistant
      Hodgkin's disease].
AB  - The authors evaluated a group of 48 patients with relapsing or resistant
      Hodgkin's disease. The patients were treated by life-saving chemotherapy followed
      by large doses of chemotherapy and autologous transplantation of haematopoietic
      cells. For life-saving chemotherapy they used most frequently a combination of
      VIM in 40 patients and combinations of DHAP, MINE, MiniDexaBEAM. In 11 patients
      they changed the regime of life-saving chemotherapy because of a poor response.
      After completed life-saving chemotherapy 18 (37.5%) patients were in CR, 27
      (56.2%) in PR and in 3 (6.3%) the disease progressed. For large dose chemotherapy
      the authors used BEAM in 32 patients, CBV in 2, Busulfan with Cyclophosphamide in
      13 patients and Busulfan with Melfalan in one patient. After completion of large
      dose chemotherapy and subsequent autologous transplantation of bone marrow 31
      (64.6%) patients were in CR, 8 (16.7%) in PR and the disease progressed in 9
      (18.7%). In August 1999 a total of 44.9% patients in CR survive, the median
      period of follow up after autologous transplantation was 23 months. Life-saving
      chemotherapy with subsequent large dose chemotherapy led in the investigated
      group to induction of CR in 64.6% patients which is the basic prerequisite of
      long-term survival.

PMID- 11227182
TI  - [Leptin levels in peripheral blood and bone marrow in orthopedic patients].
AB  - Leptin is a protein with hormonal activity and is produced mainly by adipocytes.
      Its primary function in the human organism is regulation of the calorie intake
      via the anorectic action in the hypothalamus. Leptin participates also in the
      regulation of haematopoiesis and immunity processes. There are many data on
      leptin production by peripheral adipose tissue and it is also known that leptin
      is produced by adipocytes of bone marrow. It was assumed for a long time that
      adipocytes of bone marrow are not only a passive source of energy but have,
      similarly as stromal cells, a regulatory function. However, it is not clear in
      what way the adipose tissue of bone marrow participates in the regulation of
      haematopoiesis and what role is played in this relationship by leptin production.
      The authors attempted to assemble in their small study data on leptin production
      in bone marrow and at the same time parameters of lipids of bone marrow which can
      be assessed by cytological examination. The authors examined 16 patients (9 men
      and 7 women) subjected to orthopaedic surgery. They assessed leptin
      concentrations in sera obtained from peripheral blood and bone marrow, and at the
      same time they assessed by morphological examination in smears of bone marrow
      some parameters associated with lipids. The authors found that serum leptin
      levels from bone marrow are significantly lower than in peripheral blood (p <
      0.0005). These values correlate closely (r = +0.77, p < 0.0005). The authors
      found also a positive correlation between serum leptin (r = +0.56, p < 0.02) and
      bone marrow leptin (r = +0.72, p < 0.002) and the body mass index (BMI). A
      positive correlation was found also between serum (r = +0.65, p < 0.006) and bone
      marrow leptin (r = +0.80, p < 0.0002) and age. The authors did not detect any
      significant correlations between parameters of the lipids of bone marrow and
      leptin levels in serum and bone marrow. The assembled results can in combination
      with data from the literature indicate that the actual amount of leptin in bone
      marrow is influenced rather by its consumption by haematopoietic tissue than by
      its production.

PMID- 11227183
TI  - [Levels of selenium and glutathione peroxidase in dialyzed patients].
AB  - The authors examined in 37 patients dialyzed in a dialysis centre in Brno
      Bohunice, a region with selenium deficiency in the population the serum selenium
      and glutathione peroxidase level before and after 4-hour standard haemodialysis
      across a polysulphone membrane. In 78% patients selenium deficiency was found.
      The mean value in the whole group was 33.4 micrograms Se/l. The reference range
      for the Brno population is 41.3-80.7 micrograms/l. After dialysis a rise of the
      serum selenium level by 15.4 micrograms/l occurred due to haemoconcentration
      during ultrafiltration and also due to redistribution of fluids and selenium
      during dialysis. In anuric patients selenium does not cumulate in serum, although
      it is excreted in healthy subjects mainly in the urine. Due to the closer bond
      with selenoproteins it is not significantly separated by dialysis. Glutathione
      peroxidase assessed in whole blood was in 76% patients before dialysis within the
      reference range and did not change significantly as a result of dialysis.
      Selenium deficiency participates significantly in the inadequate activity of
      antioxidant systems in the organism and in dialyzed patients it potentiates the
      development of chronic complications.

PMID- 11227184
TI  - [Treatment of hemorrhoids from the viewpoint of the gastroenterologist. Personal
      experience with the Ginkor Fort preparation].
AB  - Pathological changes in hemorhoid plexes are frequently occurring mainly in
      elderly. In development of this disease are mainly involved changes in the vessel
      wall, pressure changes in basin, disturbances in passage of stool and also
      infectious disease. Instead of the correction of the life-style in therapy are
      used locally-acting drugs whose basis are local anesthetics, spasmolytics,
      antiflogistics, antipruriginostics and corticoids in many combinations. The main
      aim of the orally administered drugs is influence of the vessel-wall tone,
      decrease of the capillary permeability, circulation betterment, decrease of the
      oedema and blockage of the inflammatory mediators. In the group of 45 patients is
      documented benefit in use of Gincor-fort in dose of 2 cps bid in first week and 2
      cps daily in the second week of the treatment. We presume that this drug can
      influence all of above mentioned factors during the acute hemorrhoidal attack.

PMID- 11227185
TI  - [Monoclonal gammapathy of undetermined significance (benign monoclonal
      gammapathy)].
AB  - Monoclonal gammapathy is a condition that may be related to the malignant
      lymphoproliferative disease, but more often to a benign lymphoproliferation.
      Formerly termed benign monoclonal gammapathy it is now called monoclonal
      gammapathy of unknown significance (MGUS), because years later malignant
      lymphoproliferative disease may develop. Even benign gammapathy may cause
      frequent symptoms in a patient. The text describes clinical manifestations of
      monoclonal protein including various differential diagnostic possibilities.

PMID- 11227186
TI  - [Treatment of renal hypertension].
AB  - In recent years in conjunction with medicamentous treatment of renoparenchymatous
      hypertension in particular two problems were discussed: target blood pressure
      values and renoprotective effects of antihypertensive drugs. Prospective studies
      revealed that a blood pressure reading of < 130/80 mm Hg significantly retards
      the progression of nephropathy whereby patients with proteinuria > 1 g/d benefit
      from even lower BP readings. In diabetic nephropathy the drugs of choice are
      inhibitors of angiotensin converting enzyme (ACEI), already in the incipient
      stage and also in normotensive patients. The importance of ACEI in the treatment
      of non-diabetic nephropathies was confirmed recently by controlled prospective
      studies AIPRI and REIN. A maximal renoprotective effect of ACEI probably calls
      for larger doses than those needed for normalization of BP. Long-term
      investigations of the renoprotective effect of antagonists of angiotensin AT1
      receptors and comparative studies with ACEI resp. are not available.
      Dihydropyridine blockers of calcium channels with a short-term action
      (nifedipine) may have a negative influence on the progression of diabetic
      nephropathy, the effect of dihydropyridines of the second generation is tested in
      prospective studies. Non-dihydropyridine calcium channel blockers have a
      renoprotective action in diabetic nephropathy. In cca two thirds of the patients
      combined treatment with ACEI and diuretics or with calcium channel blockers is
      necessary. As to other antihypertensive drugs, vasodilatating beta-blockers and
      perspectively antagonists of endothelin receptors are useful.

PMID- 11227187
TI  - [Lymphocytosis with large granular lymphocytes: case report].
AB  - Lymphoproliferative disorders of large granular lymphocytes (LGL) can arise from
      either CD3+ T cells or CD3- natural killer cells. Polyclonal proliferation of LG
      lymphocytes is called LGL lymphocytosis, monoclonal proliferation of LG
      lymphocytes is LGL leukaemia. Prominent clinical manifestations of LGL
      lymphocytosis and leukaemia are bacterial infections, splenomegaly, and may be
      connected with rheumatic or autoimmune disorders. Hematologic findings reveal
      particularly lymphocytosis, and severe neutropenia. The beta chain gene of T cell
      receptor rearrangement analysis is necessary for distinguishing of T LGL
      lymphocytosis from T LGL leukaemia. The authors report a case of young woman with
      T cells LGL lymphroproliferative disorder, bacterial infection, reactive
      lymphadenopathy, and spontaneous regression of the lymphocytosis within 6 months.

PMID- 11227188
TI  - Phenotypic and genotypic characterization of virulence factors of Escherichia
      coli isolated from broiler chickens with simultaneous occurrence of cellulitis
      and other colibacillosis lesions.
AB  - The objective of this study was to characterize virulence factors of Escherichia
      coli isolates from broilers with simultaneous occurrence of cellulitis and other
      colibacillosis lesions. Thirty flocks were sampled and 237 birds with cellulitis
      were examined. Eighty-two (34.6%) of 237 birds condemned for cellulitis had gross
      lesions in the heart, air sacs, joints, or liver. In 58 chickens, E. coli was
      isolated from both the cellulitis and other lesions of colibacillosis, and 18.9%
      of the E. coli isolates from the 2 types of lesions belonged to the same O group.
      Escherichia coli of serogroups O78, O1, and O2 predominated. Isolates of the same
      serogroup that were derived from different lesions in the same birds had similar
      patterns of biotype, aerobactin production, serum sensitivity profile, antibiotic
      sensitivity, and K1 capsule production. Escherichia coli derived from cellulitis
      lesions produced virulence factors similar to those found in E. coli isolated
      from other colibacillosis lesions in poultry.

PMID- 11227189
TI  - Testing of bulk tank milk for Salmonella Dublin infection in Danish dairy herds.
AB  - The usefulness of enzyme-linked immunosorbent assay (ELISA) was investigated as a
      simple method to screen for Salmonella Dublin infection in dairy herds, examining
      bulk tank milk samples for lipopolysaccharide (O:1,9,12) antibodies. The cut-off
      value for the ELISA on bulk tank milk was established based on individual milk
      samples (n = 2887) and bulk tank milk from 52 herds. Bulk tank milk samples (n =
      5108) were collected from 1464 dairy herds located in 19 different areas. About
      10% of the dairy herds in Denmark participated in the study. The percentage of
      herds changing from test-negative to test-positive in each area was correlated
      with the incidence of S. Dublin outbreaks in the corresponding county (r = 0.48,
      n = 19; P < 0.025). The mean level of the OD values obtained in the first and
      third test rounds was not constant (Pr /t/ = 0.0001). The study demonstrated that
      the probability of being test-negative in the third test round was 0.926 for a
      herd with 2 previous test-negative results. It was concluded that the
      investigated ELISA method was in general accordance with the cases of clinical S.
      Dublin infection recorded, and that the method has a potential for national
      screening purposes.

PMID- 11227190
TI  - An evaluation of test and removal for the elimination of porcine reproductive and
      respiratory syndrome virus from 5 swine farms.
AB  - The objective of this field study was to evaluate the protocol of test and
      removal (T&R) for the elimination of porcine reproductive and respiratory
      syndrome virus (PRRSV) from 5 chronically infected breeding herds. The T&R
      protocol involved sampling the entire breeding herd in one day, testing sera by
      polymerase chain reaction and ELISA to detect previously exposed and/or infected
      animals, and subsequently removing them from the herd. Following completion of
      T&R, breeding herds were monitored for 12 consecutive months, using ELISA, for
      the presence of antibodies to PRRSV. In order to be classified as a PRRSV
      negative herd, all samples collected over the 12-month monitoring period were
      required to be negative by ELISA (s/p ratio < 0.4). At the conclusion of the
      monitoring period, all 5 farms were PRRSV-negative, according to the defined
      testing criteria. Approximately 2.2% (74/3408) ELISA false positive samples were
      detected across all 5 farms during the monitoring period. The diagnostic cost
      required during the T&R protocol was approximately US $10.66 per animal tested.
      Limitations of the study were a lack of herds with large (> 2000 sows) breeding
      herd inventories, and herds with a history of PRRSV vaccination.

PMID- 11227191
TI  - Efficacy of a transmissible gastroenteritis coronavirus with an altered ORF-3
      gene.
AB  - Serial passage of virulent transmissible gastroenteritis virus through cell
      culture reduced its virulence in 3-day-old piglets. Intramuscular inoculation of
      pregnant gilts with 2 doses of this modified-live virus elicited a level of
      lactogenic immunity that protected their nursing piglets against a lethal dose of
      challenge virus. Sequence analysis of a 637-bp fragment of the spike gene
      containing most of the aminopeptidase receptor and the 4 major antigenic sites
      from the original and the serially passed viruses were nearly identical. Gel
      analysis revealed that the fragment from the ORF-3 gene of virulent virus was
      smaller than the corresponding fragment from the serially passed virus. Sequence
      analysis of the fragment from the passed virus revealed that the sequence between
      nt 5310 and nt 5434 was replaced by a 636-bp fragment from the polymerase 1A
      gene. This replacement resulted in the loss of the CTAAACTT leader RNA-binding
      site and ATG start codon for the ORF-3A gene but it did not affect the ORF-3B
      gene.

PMID- 11227192
TI  - In situ hybridization for the detection of transmissible gastroenteritis virus in
      pigs and comparison with other methods.
AB  - Archived formalin-fixed, paraffin-embedded tissues from 25 pigs naturally
      infected with transmissible gastroenteritis virus (TGEV) were examined by in situ
      hybridization for TGEV nucleic acid using a nonradioactive digoxigenin-labeled
      cDNA probe that targeted the nucleocapsid sequence of TGEV strains. The results
      of in situ hybridization for the detection of TGEV were compared with virus
      isolation (VI), a fluorescent antibody test (FAT), and transmission electron
      microscopy (TEM). VI, FAT, and TEM were tested over a course of time before the
      in situ hybridization was performed. Positive hybridization signals were detected
      in duodenal, jejunal, and ileal enterocytes from 21 pigs. Hybridization signals
      were confined to the cytoplasm. Intestinal specimens from 25 piglets were
      evaluated by 4 tests. Twenty-one of 25 were positive by in situ hybridization. Of
      these 21 samples, 5 (24%) were positive for TGEV by all 4 tests, 15 (71%) were
      positive by FAT, 14 (67%) were positive by VI, and 6 (29%) were positive by TEM.
      In situ hybridization for the detection of TGEV in formalin-fixed, paraffin
      embedded tissues provides a rapid means of confirmation of a histopathological
      diagnosis of TGEV without virus isolation, or when only formalin-fixed intestinal
      specimens were available.

PMID- 11227193
TI  - Phagocytic response of bovine polymorphonuclear leukocytes to different
      incubation conditions and following exposure to some effectors of phagocytosis
      and different anticoagulants in vitro.
AB  - The ability of bovine polymorphonuclear leukocytes (PMN) to phagocytose
      fluorescent beads in vitro was studied using flow cytometry. The effects of
      varying laboratory conditions (bead:PMN ratio, length of incubation, and
      temperature) were first determined, then the effects of lipopolysaccharide (LPS),
      phorbol myristate acetate (PMA), cytochalasin B, and formyl-met-leu-phe (fMLP) on
      phagocytosis were evaluated. The recommended bead:PMN ratio, incubation period,
      and incubation temperature are 20:1, 30 min, and 38.5 degrees C, respectively.
      Lipopolysaccharide increased phagocytosis at a relatively high minimum dose; PMA
      increased phagocytosis even at low doses; cytochalasin B increased and decreased
      phagocytosis at low and high doses, respectively; and fMLP had no significant
      effect on phagocytosis. Also, the effects of ethylene diamine tetraacetic acid
      (EDTA) and acid citrate dextrose (ACD) as anticoagulants were compared with
      heparin-treated blood PMNs. Both EDTA and ACD decreased phagocytosis. Although
      there are reports that demonstrated that heparin reduced PMN phagocytosis, at
      least among the 3 anticoagulants used, heparin remains to be the standard
      anticoagulant for the study of PMN phagocytosis.

PMID- 11227194
TI  - Preliminary studies of a canine 13C-aminopyrine demethylation blood test.
AB  - The objectives of this study were to determine whether a 13C-aminopyrine
      demethylation blood test is technically feasible in clinically healthy dogs,
      whether oral administration of 13C-aminopyrine causes a detectable increase in
      percent dose/min (PCD) of 13C administered as 13C-aminopyrine and recovered in
      gas extracted from blood, and whether gas extraction efficiency has an impact on
      PCD. A dose of 2 mg/kg body weight of 13C-aminopyrine dissolved in deionized
      water was administered orally to 6 clinically healthy dogs. Blood samples were
      taken from each dog 0, 30, 60, and 120 min after administration of the 13C
      aminopyrine. Carbon dioxide was extracted from blood samples by addition of acid
      and analyzed by fractional mass spectrometry. None of the 6 dogs showed any side
      effects after 13C-aminopyrine administration. All 6 dogs showed a measurable
      increase of the PCD in gas samples extracted from blood samples at 30 min, 60
      min, and 120 min after 13C-aminopyrine administration. Coefficients of variation
      between the triplicate samples were statistically significantly higher for the
      %CO2, a measure of extraction efficiency, than for PCD values (P < 0.0001). The
      13C-aminopyrine demethylation blood test described here is technically feasible.
      Oral administration of 13C-aminopyrine did not lead to gross side effects in the
      6 dogs. Clinically healthy dogs show a measurable increase of PCD in gas
      extracted from blood samples after oral administration of 13C-aminopyrine.
      Efficiency of CO2 extraction from blood samples does not have an impact on PCD
      determined from these blood samples. This test may prove useful to evaluate
      hepatic function in dogs.

PMID- 11227195
TI  - Comparison of abomasal emptying in neonatal calves with a nuclear scintigraphic
      procedure.
AB  - The purpose of the present study was to demonstrate that nuclear medicine
      technology allows observation of the effect that milk clotting has on abomasal
      emptying in the living neonatal calf. Scintigraphic evaluation of abomasal
      emptying was carried out in 6 healthy male Holstein calves. The calves were fed
      10% of their body weight daily as whole cow's milk that was divided equally and
      consumed as 2 feedings via a nipple bottle. One day before the nuclear
      scintigraphic procedure, the calves were randomly fed whole cow's milk, or an
      oral rehydration solution (ORS) containing bicarbonate and high levels of soluble
      fibre was fed for 3 consecutive feedings an hour before the portion of milk. For
      each calf, both feeding programs were repeated twice at a one-week interval.
      Immediately following administration of the 99mTC-sulfur-colloid-containing milk,
      the calves were imaged with the gamma camera positioned lateral and ventral to
      the abomasum. Additional right lateral and ventral views of the abomasum were
      collected at 15, 30, 45, 60, 90, 120, 150, 180, 210, and 240 min after
      administration of the radionuclide. Blood glucose determination were performed at
      one-hour intervals for 7 h after feeding milk to evaluate milk digestibility in
      both feeding programs. No significant differences in the results of the glucose
      absorption test or in the radionuclide counts of the abomasum were found between
      both feeding programs. Scintigraphic evaluation of abomasal emptying was found to
      be a useful technique for visualization of milk clotting and to test the effect
      of an ORS on milk digestibility.

PMID- 11227196
TI  - Effects of a histamine type 2 receptor antagonist, BMY-26539-01, on equine
      gastric acid secretion.
AB  - A dose-response study was undertaken of the effects of a newly developed
      histamine type 2 receptor antagonist, BMY-26539-01, on gastric acid secretion in
      4 fasted horses. Doses of 0.1 mg/kg, 0.3 mg/kg, 0.5 mg/kg, or placebo were
      administered in a randomly assigned treatment sequence. Hydrogen ion
      concentration and pH were variable during baseline measurements in all 4 animals;
      however, following BMY-26539-01 administration, mean pH increased and hydrogen
      ion concentration decreased in a dose-related pattern. At the 0.3 mg/kg and 0.5
      mg/kg dose levels, pH remained elevated for > 4 h and > 8 h, respectively. No
      adverse effects were observed. A significant level of 0.01 was used for all
      statistical methods.

PMID- 11227197
TI  - Effects of GnRH treatment on scrotal surface temperatures in bulls.
AB  - Two experiments were conducted to characterize scrotal surface temperature (SST)
      in bulls treated with gonadotropin releasing hormone (GnRH). In Experiment 1,
      Angus bulls (n = 10, 18 mo, 597 kg) were given GnRH (400 ng/kg) or saline, IV.
      Bottom SST increased approximately 1.7 degrees C (P < 0.005) over time (0 to 90
      min) at an ambient temperature of 5 degrees C. However, there was no significant
      effect of GnRH treatment and temperature increases were attributed to stress.
      When the experiment was repeated at an ambient temperature of 25 degrees C, SST
      was elevated prior to treatment, with no subsequent significant increase.
      Experiment 2 was conducted with Charolais bulls (n = 6, 12-14 mo, 517 kg) with an
      emphasis on minimizing stress. Bottom SST increased approximately 2 degrees C (P
      < 0.05) between 0 and 45 min after GnRH treatment, supporting the hypothesis that
      GnRH treatment increases SST in bulls. In conclusion, it was apparent that
      stress, high ambient temperatures, and GnRH treatment can all increase SST in
      bulls.

PMID- 11227198
TI  - Pharmacokinetics of enrofloxacin after intravenous and intramuscular
      administration in Angora goats.
AB  - Pharmacokinetics and bioavailability of enrofloxacin were determined after single
      intravenous (IV) and intramuscular (IM) administrations of 5 mg/kg body weight
      (BW) to 5 healthy adult Angora goats. Plasma enrofloxacin concentrations were
      measured by high performance liquid chromatography. Pharmacokinetics were best
      described by a 2-compartment open model. The elimination half-life and volume of
      distribution after IV and IM administrations were similar (t1/2beta, 4.0 to 4.7 h
      and Vd(ss),1.2 to 1.5 L/kg, respectively). Enrofloxacin was rapidly (t1/2a, 0.25
      h) and almost completely absorbed (F, 90%) after IM administration. Mean plasma
      concentrations of enrofloxacin at 24 h after IV and IM administration (0.07 and
      0.09 microg/mL, respectively) were higher than the minimal inhibitory
      concentration (MIC) values for most pathogens. In conclusion, once-daily IV and
      IM administration of enrofloxacin (5 mg/kg BW) in Angora goats may be useful in
      treatment of infectious diseases caused by sensitive pathogens.

PMID- 11227199
TI  - Specific detection by PCR of Streptococcus agalactiae in milk.
AB  - The aim of this study was to develop a simple and specific method for direct
      detection of Streptococcus agalactiae from cow's milk. The method was based on
      polymerase chain reaction (PCR) using species-specific and universal primers
      derived from the 16S rRNA gene. The amplification product was verified by
      restriction endonuclease digest and sequencing. Specific identification was
      proven on a collection of 147 S. agalactiae isolates of bovine and human origin.
      In addition, 17 strains belonging to different bacterial species that potentially
      can be found in milk samples also tested negative. The PCR developed was used for
      direct detection of S. agalactiae in milk, using for the first time with gram
      positive bacteria the nucleic acid-binding properties of diatomaceous earth. The
      test, which has high specificity, high sensitivity (100 cfu/mL), and can be
      carried out in less than 24 h, represents an innovative diagnostic tool for the
      detection of S. agalactiae in milk.

PMID- 11227200
TI  - Seasonal incidence and antibiotic susceptibility patterns of Pasteurellaceae
      isolated from American bison (Bison bison).
AB  - Ninety pharyngeal tonsils were collected from 2-year-old American bison (Bison
      bison) bulls and sampled for members of the Pasteurellaceae family. Particular
      attention was paid to seasonal incidence and antimicrobial resistance in
      serotypes and biovariants. Multiple strains of Pasteurella haemolytica (39%), P.
      trehalosi (68%), P. multocida (34%) and Haemophilus somnus (13%) were cultured
      from 86 out of the 90 (96%) tonsil samples. Pasteurella trehalosi was the most
      common and evenly distributed of the organisms recovered. Pasteurella haemolytica
      was found in fewer numbers than P. trehalosi, but showed an increase in number of
      isolates recovered with each sampling period. Pasteurella multocida, both A and D
      capsular types, was recovered from all sampling periods. No serotype pattern was
      observed in any of the animal groups sampled. One hundred twenty-seven of 147
      (86%) of the isolates were resistant to at least 1 antibiotic, 95/147 (65%) to at
      least 2 different antibiotics, and 16/147 (11%) to at least 3 antibiotics. The
      most common resistance pattern observed was to neomycin and spectinomycin
      (73/147) (49%).

PMID- 11227201
TI  - Very low prevalence of bovine immunodeficiency virus infection in western
      Canadian cattle.
AB  - Bovine immunodeficiency virus (BIV) is a lentivirus that causes disease in
      cattle. Despite the large cattle industry in western Canada, the presence of BIV
      has not been examined to date. Genomic DNA, derived from semen and buffy coat
      samples, was analyzed by nested polymerase chain reaction (PCR) using specific
      primers for the gag, pol, and env genes of BIV. Despite utilizing a procedure
      that detected a minimum of 10 proviral copies, BIV sequences were not amplified
      in any of 317 buffy coat and 50 semen samples that were obtained from an archive
      that included 27 cattle breeds, collected from different sources in Alberta (1980
      1999). In the 367 DNA samples examined, there was no evidence of BIV infection,
      suggesting that the prevalence of BIV infection was very low.

PMID- 11227202
TI  - Pyrexia of undetermined origin in the era of HAART.

PMID- 11227203
TI  - Clinical implication of Roux's concept in orofacial orthopedics.
AB  - Long-term follow-up studies have revealed that the shields of the function
      regulator are capable of influencing the circumoral soft tissue capsule in size
      and shape. As a result, the disturbed or restricted displacement of teeth and jaw
      bones could be corrected. The dramatic changes in dentoskeletal development thus
      achieved demonstrate the morphogenetic impact of the circumoral capsule. In
      clinical application, the function regulator offers the opportunity to realize
      Roux's concept of functional orthopedics in the treatment of orofacial
      dysmorphology, as has long been practiced in the medical field of orthopedics.

PMID- 11227204
TI  - Tablet fluoridation influences the calcification of primary tooth pulp.
AB  - This study was conducted to determine the influence of long-term tablet
      fluoridation on primary pulp calcification by light microscopy. Twenty-four
      caries-free primary molars (after continuous postpartally initiated 1- to 10-year
      tablet fluoridation) were compared to 17 primary molars of children without
      fluoride prophylaxis. Pulp calcification in children with tablet fluoridation was
      significantly more frequent and more pronounced than in untreated children (p =
      0.001). Besides the known pulp stones, the prophylaxis group evidenced a special
      form of calcification consisting of fibrodentin-like hard tissue not observed in
      the untreated children. These hard tissue bodies developed "intramurally" on the
      pulp floor and the inside of the dental roots with an irregular extramural spread
      into the coronal and radicular pulp by displacement and fibrotization of the pulp
      tissue. Moreover, some of the teeth had more or less extensive areas of
      interglobular dentin. The affected teeth were ankylosed in the area of the bi-
      and trifurcation and on the inside of the roots and were thus infra-occluded.
      Although the duration of tablet fluoridation has no statistically significant
      influence on pulp calcification, there is a correlation between extensive pulp
      calcification, postnatally initiated fluoride prophylaxis and the infraocclusion
      of primary molars.

PMID- 11227205
TI  - Influence of repeated chlorhexidine varnish applications on mutans streptococci
      counts and caries increment in patients treated with fixed orthodontic
      appliances.
AB  - The occurrence of new carious lesions is among the most detrimental side effects
      in subjects undergoing orthodontic therapy with fixed appliances. The present
      study evaluated the efficacy of repeated applications of a 40% chlorhexidine
      varnish in this patient group with regard to long-term suppression of elevated
      mutans streptococci levels and the frequency and location of new carious lesions.
      Thirty-three prospective orthodontic patients age 11 to 18 harboring more than
      10(5) mutans streptococci per ml saliva at the initial examination participated
      in the study. At baseline the previous carious involvement in each subject was
      recorded using the DMFS index, and extensive information on caries prevention was
      given. Using a random assignment 18 subjects were included in the test group
      while the remaining 15 subjects were assigned to the placebo group. From the time
      of banding until removal of the fixed appliances (median: 21 months) salivary
      mutans streptococci counts were recorded once every 8 weeks in both groups. At
      the same appointments all teeth and introaral appliances in the test group were
      coated with a 40% chlorhexidine varnish. Subjects in the placebo group were
      treated in the same way, using a placebo varnish with the same varnish base.
      After debanding, the DMFS score of each participant was recorded again. Analysis
      of the data revealed that mutans streptococci counts in the test group were only
      temporarily suppressed and were restored almost to baseline levels by the end of
      the study.  In both groups a clinically relevant increase in the average DMFS
      score was recorded.  Inter-group differencies were not significant.

PMID- 11227206
TI  - Functional improvement of the mandibular neuromuscular guidance by orthodontic
      surgical treatment.
AB  - The primary aim of the study was to reveal whether adult patients with skeletal
      mandibular retrognathism combined with a dental Class II relationship without
      craniomandibular pain show a characteristic pattern of free mandibular movements
      compared to patients with a Class I skeletal and dental morphology. The secondary
      aim was to investigate whether these characteristic structures are subject to
      change following combined orthodontic-surgical treatment. Free mandibular
      movements were measured with an ultrasound device and analyzed with computer
      software developed by the authors. In all patients examined, 2 maxillarily and
      mandibularly fixed axes were found. These axes have no direct relation to the
      temporomandibular joints, are positioned above and anterior to the joints and
      maintain a constant distance. This gear system is referred to as a
      neuromuscularly determined dimeric link chain. The position of the mandible is
      defined by the rotational angle mu and the inclination angle alpha around the
      axes of the dimeric link chain. This dimeric link chain of free movements of
      patients with Class I skeletal and dental relationship functions according to the
      principle of least action: The angular velocities around the 2 axes show a
      constant ratio within the different segments of motion, and in the mu-alpha
      diagrams the segments of mandibular movements are represented by straight lines,
      the shortest paths between 2 positions. Individual cases and statistical data
      show that the structure of mandibular movements of patients with skeletal
      mandibular retrognathism combines with a dental Class II relationship without
      craniomadibular pain differs significantly from that of patients with Class I
      alignment.  Mandibular retrognathism and a Class II relationship are accompanied
      by marked coordination disturbances in the rotary movements around the maxillary
      and mandibular neuromuscular axes.  Following orthodontic-surgical treatment to
      restore ideal alignment of the occlusal, articular, and skeletal structures, the
      patients showed a similar pattern in the structure of mandibular movements to
      that of patients with Class I sketal and dental relationships.  Thus, combined
      orthodontic-surgical treatment leads to measurable functional hamonization not
      only of the skeletal and dental structures but also of the neuromuscular guidance
      system.

PMID- 11227207
TI  - Differences between two transpalatal arch systems upon first-, second-, and third
      order bending activation.
AB  - Transpalatal arches are used in passive mode to improve anchor-age and in
      activated mode to achieve single tooth movement or movement of segments of teeth
      in first-, second- and third-order. Clinically it seems that the commonly used
      palatal arches of the Goshgarian type (here in the MIA system) as well as the
      precision TMA lingual arches of the Burstone system are not equally suitable for
      all kinds of activations. Using the Orthodontic Measurement and Simulation System
      (OMSS) the force systems and the efficacy of activated arches of both systems
      were examined in an experimental study with respect to different malpositions.
      The following first-, second- and third-order activations were chosen:
      symmetrical expansion and compression up to 4 mm, symmetrical distal rotation up
      to 15 degrees, unilateral distal tipping of 15 degrees and symmetrical buccal
      root torque up to 10 degrees. Attachments of the MIA system (MIA Rotation Lingual
      Sheaths, 0.072" x 0.036") and of the Burstone system (precision lingual hinge
      cap, 0.032" x 0.032", unused and a pair after a 4-week introral application
      period) were measured. Lingual arches made of 0.036" round stainless steel wire
      (MIA) and 0.032" x 0.032" TMA (Burstone system) were prepared with a height of 18
      mm and a width of 30 mm. First-order activation bends (expansion and compression)
      of the MIA palatal arches caused forces up to 4.4 N compared to 1.8 N of the TMA
      arches, due to the lower load/deflection rate of the latter. The malpositions
      were corrected effectively by both systems. Due to the higher stiffness the
      moments delivered by the MIA palatal arches (39 Nmm) were higher in distal
      rotation compared to those of the TMA arches (14 Nmm) and the correction was more
      effective. In second-order activations (tipping) the MIA system delivered no or
      only small moments because of the curved shape of the attachments. A correction
      of only 30% was achieved compared to 80% with the Burstone system. In third-order
      activations, in contrast, the Burstone attachments caused considerable loss of
      torque. This was obviously due to the strong deformation of the slot by the
      intraoral loading. If it were possible to improve the dimensional stability of
      the hinge cap, all corrections carried out with the Burstone TMA system would
      involve distinctly smaller forces and moments than the MIA system but would still
      ensure good effectiveness.

PMID- 11227208
TI  - Impact factor. A review with specific relevance to orthodontic journals.
AB  - The aim of this article is to address the issues of impact factor and circulation
      with reference to dental and orthodontic journals by discussing various
      parameters including language, citations, nature of published articles, and
      scientific domain. Examples from the literature are provided to illustrate the
      variability of impact factors among periodicals, based on the publicity and
      scientific area covered, and the impact factor scores are presented together with
      the circulation of orthodontic periodicals.

PMID- 11227209
TI  - CD47 and death signaling in the immune system.
AB  - Receptor-mediated death signaling plays a critical role both in proper control of
      immune responses and in killing of target cells by T cells. In addition to the
      recognized death receptors which all belong to the tumor necrosis factor receptor
      family, recent studies suggest that also other cell surface antigens may be
      involved in apoptotic signaling in the immune system. New data on the Ig family
      member CD47 implicate a functional role of this molecule in growth regulation of
      lymphocytes and suggest that the antigen mediates cell death by activating a non
      classical form of apoptosis. This mini review will focus on CD47 as a possible
      death receptor on lymphocytes and also summarize some of the current knowledge on
      death control in the immune system.

PMID- 11227210
TI  - Apoptosis, cross-presentation, and the fate of the antigen specific immune
      response.
AB  - Induction of cell death by apoptosis, also called programmed cell death, and
      clearance of apoptotic bodies by scavenger cells has long thought to be an
      efficient means to dispose of unwanted cells without causing inflammatory
      responses able to mediate specific reactions. However, a number of evidences have
      been accumulated suggesting that apoptotic cell death is implicated in the
      pathogenesis of systemic and organ specific autoimmune diseases. In addition,
      recognition and engulfement of apoptotic cells by professional antigen presenting
      cells, such as dendritic cells, and their interaction with effector immune cells
      have been recently described to result in apoptotic cell-derived antigen specific
      tolerance. This review will summarise the most recent findings on the immunogenic
      potential of cells undergoing programmed death.

PMID- 11227211
TI  - Bcr-Abl and inhibition of apoptosis in chronic myelogenous leukemia cells.
AB  - Chronic myelogenous leukemia (CML) cells are highly resistant to apoptosis
      induced by chemotherapeutic drugs. The observation that production of Bcr-Abl is
      the initiating event in CML has focussed attention on the survival signals
      triggered by this oncogene. A number of signal transducers and transcription
      factors have been associated with the antiapoptotic phenotype of CML cells, some
      of which lead to the expression and/or activation of members of the Bcl-2 family
      of apoptosis modulators, such as Bcl-xL and Bad. In this article, recent advances
      in understanding the antiapoptotic pathways triggered by Bcr-Abl in CML cells,
      are discussed.

PMID- 11227212
TI  - Aminodipeptidase inhibitor-induced cell death in quiescent lymphocytes: a review.
AB  - We recently isolated and cloned an intracellular post-proline cleaving
      aminodipeptidase, quiescent cell proline dipeptidase (QPP), which has a substrate
      specificity very similar to that of dipeptidyl peptidase IV (CD26/DPPIV). Highly
      specific inhibitors of proline aminodipeptidases activate a novel apoptotic
      pathway in quiescent lymphocytes. The target of these inhibitors is not
      CD26/DPPIV, but appears to be QPP. The apoptosis pathway induced by the
      aminodipeptidase inhibitors is unusual in that it is restricted to quiescent
      lymphocytes, but not activated or transformed lymphocytes. The caspases activated
      in this apoptotic pathway are different from those activated in Fas or gamma
      irradiation mediated cell death pathways, and furthermore, the proteasome appears
      to play a role in this death pathway. A large number of signal molecules
      including chemokines and cytokines have a highly conserved X-Pro motif on the N
      terminus, rendering them potential substrates of QPP and players in the survival
      of resting lymphocytes.

PMID- 11227213
TI  - Endothelial cell survival and apoptosis in the tumor vasculature.
AB  - Angiogenesis is essential for the growth and metastasis of solid tumors. The
      balance of endothelial cell (EC) proliferation and apoptosis is a major
      determinant in tumor angiogenesis. Recently, several studies demonstrated that
      numerous angiogenic factors not only induce angiogenesis but also function as EC
      survival factors. Vascular endothelial growth factor (VEGF), a potent angiogenic
      factor, is also an EC survival factor in embryonic vasculogenesis and tumor
      angiogenesis. VEGF activates specific intracellular survival pathways in ECs
      including Bcl-2, A1, IAP, Akt, and Erk. Integrins may function as EC survival
      factors by preventing anoikis by enhancing binding to the extracellular matrix.
      In addition, integrins may function in concert with VEGF to promote EC survival.
      Angiopoietin-1 (Ang-1) has recently been shown to stabilize EC networks by
      binding to the EC-specific tyrosine kinase receptor Tie-2. Pericytes also
      function as EC survival factors, by cell-cell contact, secretion of survival
      factors, or both. Targeting any of the above mechanisms for EC survival may
      provide novel antineoplastic strategies.

PMID- 11227214
TI  - False-positive apoptosis signal in mouse kidney and liver detected with TUNEL
      assay.
AB  - Apoptosis is a physiological, programmed process for the elimination of cells
      from living organisms. Currently, one of the most frequently used methods to
      detect apoptosis is TUNEL assay. It has provided valuable information about
      apoptosis in various tissues. However, the sensitivity and the specificity of
      TUNEL technique have also been criticized. We detected an intense false-positive
      apoptotic signal in nude and Balb/c mice kidney and liver. In kidney the signal
      was confined to the proximal, distal and collecting tubular cells, and in liver
      to hepatocytes. Both tissues appeared normal in light microscopy, and no DNA
      ladder formation or increase in caspase-3 enzyme activity was detected. BrdU
      labelling and Ki-67 immunostaining did not reveal increased cell proliferation in
      these tissues. On the other hand, false-positive signal was not detected in
      testis, spleen, pancreas or renal cell carcinoma from the same animals. Also, no
      false-positive signal was seen in human liver or kidney samples. Although factors
      known to produce false-positive staining related to sample harvesting,
      preparation and staining protocols were eliminated, the cause of the false-
      positive apoptotic signal remains unknown. We conclude that caution must be
      exercised when examining apoptosis in mouse tissues with TUNEL assay.

PMID- 11227215
TI  - Bcl-2 protects neuronal cells against taxol-induced apoptosis by inducing multi
      nucleation.
AB  - Taxol-induced peripheral neuropathy is a commonly-occurring side-effect in the
      treatment of cancer patients with taxoteres or taxanes. Taxol is known to induce
      apoptosis in a number of tumor cells. This report documents that, similar to
      proliferating cells, taxol induces apoptosis in NGF-differentiated PC12 cells, as
      assessed by exogenous FITC-annexin-V binding and nuclear fragmentation. It is
      shown that PC12 cells that stably overexpress Bcl-2 are protected against the
      toxic effect of taxol, as evidenced by the XTT assay and by a decreased fraction
      of propididum iodide positive cells in a dye exclusion test. Also the number of
      annexin-V-positive cells and the number of fragmented nuclei are lower in the Bcl
      2 transfected cells. The effect is similar to the protective effect of Bcl-2
      against NGF deprivation in differentiated PC12 cells. Although taxol forced both
      wild-type and Bcl-2-overexpressing cells into a mitotic state, only in Bcl-2
      overexpressing cells did this lead to the appearance of metabolically active,
      multi-nucleated cells. This suggests that Bcl-2 is able to induce an alternative
      escape pathway, downstream of the G2/M block, in taxol-treated differentiated
      PC12 cells.

PMID- 11227216
TI  - Induction of apoptosis in human cancer cells by TZT-1027, an antimicrotubule
      agent.
AB  - TZT-1027, a newly synthesized dolastatin 10 derivative, is a potent antitumor
      agent which inhibits microtubule polymerization and perturbs microtubule
      dynamics. In this report, we investigated whether TZT-1027 inhibited the growth
      of various human cancer cells, and the cell death caused by TZT-1027 was due to
      apoptosis. In addition, we elucidated the apoptosis machinery induced by
      treatment with TZT-1027. The 50% growth-inhibitory concentrations (IC50 values)
      of TZT-1027 on cancer cells derived from various sources were not more than 5.9
      ng/ml. TZT-1027 showed superior cytotoxicity than any other antitumor agents.
      Next, we evaluated morphological nuclear change, namely, chromatin condensation
      and DNA fragmentation. We used three cancer cell lines derived from different
      types in view of having apoptosis related protein, human leukemia HL-60 (in the
      presence of both Caspase-3 and Bcl-2), human breast cancer MCF-7 (in the absence
      of Caspase-3), and human prostate cancer DU145 (in the absence of Bcl-2). TZT
      1027 induced DNA fragmentation in the presence but not absence of Caspase-3.
      Nevertheless, apoptic chromatin condensation was observed in all cancer cells
      even if there was no Caspase-3. Furthermore, we examined whether TZT-1027,
      microtubule-disrupting agent, influenced cell cycle progression. Flow cytometric
      analysis revealed the cells treated with TZT-1027, and with the other
      antimicrotubule agents, to be arrested at the G2/M phase and subsequently to show
      fragmented DNA smaller than that of G1 phase cells. Moreover, we tested TZT-1027
      for its ability to induce Bcl-2 phosphorylation in human cancer cell lines. TZT
      1027 and other agents which interacted with microtubules induced Bcl-2
      phosphorylation, whereas DNA-damaging agents did not. The present results
      suggested an association of the growth-inhibitory effect of TZT-1027 with the
      induction of apoptosis and indicated that the apoptosis induced by TZT-1027 was
      followed by G2/M arrest even if there was no Caspase-3 or Bcl-2.

PMID- 11227217
TI  - Increased apoptosis and increased clonogenic survival of 12V-H-ras transformed
      rat fibroblasts in response to cisplatin.
AB  - Mutationally activated Ras is involved in tumor progression and likely also in
      drug resistance. Using survival, viability and apoptosis assays, we have here
      compared the cisplatin sensitivities of FR3T3 rat fibroblasts and a 12V-H-ras
      transformed subline (Ras2:3). Around 24 h after cisplatin treatment Ras2:3 cells
      showed higher apoptosis levels and lower viability than FR3T3. This increased
      sensitivity correlated with weaker cisplatin-induced activation of Jun N-terminal
      kinase (JNK). In contrast to apoptosis assays, colony formation assays showed
      that Ras2:3 were more resistant to cisplatin than were FR3T3. This was partly due
      to the increased cisplatin sensitivity of FR3T3 seeded at low densities, as
      required in colony formation assays. In addition, Ras2:3 cisplatin survivors had
      a higher relative proliferative capacity. Cell cycle analyses showed that FR3T3
      cells initially responded with a dose-dependent G2 arrest, while Ras2:3
      accumulated in S-phase. Experiments with an anti-apoptotic mutant of MEKK1
      suggested that the apoptotic response of Ras2:3 cells is not specific to the S
      phase fraction. In summary, the cisplatin response of ras-transformed fibroblasts
      is distinct from that of parental cells, in that they show increased apoptosis, a
      different cell cycle response and increased post-treatment proliferative
      capacity. The results illustrate the need to carefully consider methods and
      protocols for in vitro studies on chemotherapy sensitivity.

PMID- 11227218
TI  - Concanavalin A induced apoptosis in murine macrophage PU5-1.8 cells through
      clustering of mitochondria and release of cytochrome c.
AB  - Concanavalin A (ConA), normally a mitogen of T-lymphocytes, was found to be a
      cell cycle-independent apoptosis-inducing agent in cultured murine macrophage PU5
      1.8 cells. This assertion is based on the following observations: (1) ConA
      increased the number of cells with hypodiploid DNA in a dose dependent manner as
      revealed by flow cytometry; (2) ConA elicited DNA fragmentation and the
      cytotoxicity of ConA was suppressed by alpha-D-methylmannoside which blocks the
      lectin site of ConA; (3) ConA was able to release cytochrome c (cyto c) into the
      cytosol of PU5-1.8 cells. When isolated mitochondria were incubated with ConA,
      release of cyto c was observed too. Interestingly, clustering of mitochondria was
      found in the cytosol under a confocal microscope after ConA treatment. When cells
      were incubated with ConA-FITC and subsequently with mitotracker red (a probe for
      mitochondria), co-localization of fluorescence signals was observed. These
      results suggest that ConA was delivered to the mitochondria, induced
      mitochondrial clustering and released cyto c. Our results also show that
      introduction of exogenous cyto c electroporationally into ConA-untreated cells
      elicited DNA fragmentation. On the other hand, introduction of specific antibody
      against cyto c into PU5-1.8 cells suppressed the ConA-mediated cell death. Taken
      together, our results indicate that ConA induced apoptosis in PU5-1.8 cells
      through mitochondrial clustering and release of cyto c and the release of cyto c
      was sufficient to elicit apoptosis in PU5-1.8 cells.

PMID- 11227219
TI  - Suicidal differential housekeeping gene activity in apoptosis induced by DCNP.
AB  - Previous suggestions of CpG-specific apoptotic commitment implied critical
      epigenetic modulation of housekeeping genes which have canonical CpG islands at
      5' promoter regions. Differential housekeeping gene activity however has not been
      shown. Using a focussed microarray (genechip) of 22 housekeeping genes we show
      this in apoptosis induced in human Chang liver cells by DCNP (2,6-dichloro-4
      nitrophenol), a non-genotoxic inhibitor of sulfate detoxification. 3-7 folds
      downregulation of 9 genes in glycolysis, tricarboxylic acid cycle and the
      respiratory electron transport chain suggested gene-directed energy depletion
      which was correlated with observed ATP depletion. 4 folds downregulation of the
      pyruvate dehydrogenease gene suggested gene-directed metabolic acidosis which was
      correlated with observed cell acidification. Other differential housekeeping gene
      activity, including 4 folds upregulation of microtubular alpha-tubulin gene, and
      2 folds upregulation of ubiquitin, also had a bearing on apoptosis. Broadspectrum
      zVAD-fmk caspase inhibition abolished 200 bp DNA ladder fragmentations but not
      the CpG-specific megabase fragmentations and other hallmarks of cell destruction,
      suggesting a caspase-independent cell death. Death appeared committed at gene
      level.

PMID- 11227220
TI  - Activities and interactions among phospholipases A2 during thapsigargin-induced
      S49 cell death.
AB  - The purpose of this study was to determine the roles of calcium-dependent
      phospholipase A2 (cPLA2) and calcium-independent phospholipase A2 (iPLA2) in
      thapsigargin-induced membrane susceptibility to secretory phospholipase A2
      (sPLA2) and programmed cell death. 3H-arachidonic acid release was observed in
      the presence of thapsigargin. This release was inhibited partially by an
      inhibitor of iPLA2 (BEL) and completely by an inhibitor of both cPLA2 and iPLA2
      (MAFP) suggesting that these enzymes were active during apoptosis. The process of
      cell death did not require the activity of either enzyme since neither inhibitor
      impeded the progression of apoptosis. However, both inhibitors increased the
      susceptibility of the membrane to sPLA2 in the presence of thapsigargin. In the
      case of BEL, this effect appeared to involve direct induction of apoptosis in a
      sub-population of the cells independent of the action of iPLA2. In conclusion,
      the results suggested that cPLA2 and iPLA2 are active during thapsigargin-induced
      apoptosis in S49 cells and that cPLA2 tempers the tendency of the cells to become
      susceptible to sPLA2 during apoptosis.

PMID- 11227221
TI  - Midwifery debate.

PMID- 11227222
TI  - AFNC clarifies stance.

PMID- 11227224
TI  - The Medicare Benefits Act.

PMID- 11227223
TI  - Hydromorphone.

PMID- 11227225
TI  - Let the user beware. OTC drugs aren't necessarily 'safe when taken as directed.'.

PMID- 11227226
TI  - The impact of staff nurses on the recruitment of patients.

PMID- 11227227
TI  - Emergency: Anterior shoulder dislocation.

PMID- 11227228
TI  - The proverbial herb.

PMID- 11227229
TI  - Speaking the language of pain.

PMID- 11227230
TI  - Workplace advocacy. How can it help you?

PMID- 11227231
TI  - Dying for relief. When pain relief could result in death.

PMID- 11227232
TI  - Palliative care and lung transplantation: conflict or continuum?

PMID- 11227233
TI  - Stump care.

PMID- 11227234
TI  - Promoting health literacy. Patient teaching is a vital nursing function.

PMID- 11227235
TI  - Entry into practice in Ontario. A new initiative may have implications for
      American nursing.

PMID- 11227236
TI  - History repeats. Nurses who endured racial injustice work, in their retirement,
      to broaden access to care.

PMID- 11227237
TI  - Take care of yourself. How to assess and improve safety in your workplace.

PMID- 11227238
TI  - [Results of cholecystectomy realized 10 years ago].
AB  - BACKGROUND: The "post cholecystectomy" syndrome comprises a series of vague
      symptoms referred by patients subjected to this surgical procedure. These
      symptoms are unspecific and their association with the operation is dubious. AIM:
      To assess the frequency of digestive symptoms among patients subjected to a
      cholecystectomy ten years ago. PATIENTS AND METHODS: One hundred patients
      subjected to a cholecystectomy between 1987 and 1990, were contacted by mail.
      They were invited to a clinical interview and to an abdominal ultrasound
      examination. RESULTS: Two invited patients had died of an acute myocardial
      infarction. Therefore, 98 patients (78 women), aged 30 to 85 years old, were
      assessed. Seventy two percent had diverse dyspeptic symptoms, 90% had no food
      intolerance and 94% had gained weight after the operation. Ninety six percent was
      satisfied with the surgical results, 3% had severe symptoms due to
      gastroesophageal reflux or depression. One patient had a residual
      choledocholithiasis and refused any treatment. CONCLUSIONS: Cholecystectomy is
      well tolerated and has good long term results.

PMID- 11227239
TI  - [Early erythropoietin use for the prevention of anemia in infant premature].
AB  - BACKGROUND: Anemia is common among very low birth weight newborns and requires
      frequent blood transfusions. Erythropoietin was been reported to be useful in the
      prevention of this anemia. AIM: To assess the benefits of early (before the third
      week of life) Human recombinant Erythropoietin (r-EPO) administration to reduce
      the requirement of blood transfusions in very low birth weight newborns. PATIENTS
      AND METHODS: Sixty newborns under 1500 g of birthweight were randomly assigned to
      receive r-EPO (n = 29) or placebo (n = 31) three times per week, during four
      weeks. Packed red cell volume and reticulocyte counts were measured weekly. Serum
      erythropoietin was measured prior to eighth dose. Transfusion requirements were
      recorded. RESULTS: r-EPO reduced transfusions from 1.41 +/- 1.1 to 0.69 +/- 1
      transfusions/newborns (p < 0.001). At the fourth week of treatment, reticulocyte
      count was 14.8 +/- 7 and 6.4 +/- 4.9% in the active treatment group and placebo
      group respectively (p < 0.001). CONCLUSIONS: r-EPO reduces the requirement of
      transfusions in low birth weight infants.

PMID- 11227240
TI  - [In vitro comparative activity of moxifloxacin and other antimicrobials against
      respiratory pathogens].
AB  - BACKGROUND: Respiratory pathogens are becoming increasingly resistant to
      antimicrobials. A new group of drugs, called respiratory quinolones have been
      synthesized to overcome this problem. AIM: To study the in vitro susceptibility
      of respiratory pathogens to old and new antimicrobials. MATERIALS AND METHODS:
      Forty five strains of S pneumoniae, 44 strains of H influenzae, 21 strains of M
      catarrhalis, 10 strains of methicillin susceptible S aureus and 20 strains of
      methicillin resistant S aureus were studied. All were isolated from community
      acquired respiratory infections during 1999. Minimal inhibitory concentrations of
      moxifloxacin, amoxicillin, amoxicillin/clavulanic acid, clarithromycin,
      azithromycin, ciprofloxacin and levofloxacin were determined using the Etest
      method. Beta-lactamase production by H influenzae and M catarrhalis was also
      studied. RESULTS: S pneumoniae strains were 100% susceptible to quinolones and
      cotrimoxazole, 2% were resistant to macrolides, 11% were resistant to
      amoxicillin/clavulanic acid and 47% were resistant to cefuroxime. H influenzae
      was 100% susceptible to quinolones, azithromycin and amoxicillin/clavulanic acid.
      There was a 53% resistance to cotrimoxazole, 21% to amoxicillin, 9% to
      clarithromycin and 7% to cefuroxime. M catarrahalis was 100% susceptible to
      quinolones and 100% resistant to amoxicillin, 5% resistant to macrolides, 14%
      resistant to amoxicillin/clavulanic acid, 20% to cefuroxime and 30% to
      cotrimoxazole. Methicillin susceptible S aureus was susceptible to all
      antimicrobials and methicillin resistant S aureus was resistant to all.
      CONCLUSIONS: Maxifloxacin and the new respiratory quinolones can be useful in the
      treatment of respiratory infections.

PMID- 11227241
TI  - [Thromboembolic risk factors in atrial flutter. Transesophageal echocardiographic
      study].
AB  - BACKGROUND: The thromboembolic risk of atrial flutter (AFL) is not well defined.
      On the other hand, in atrial fibrillation (AF), the echocardiographic
      demonstration of thrombus or spontaneous echo contrast in the left atria or its
      appendage, a lower flow velocity in the left atrial appendage, and its reduced
      mobility, are well known risk factors of thromboembolism. AIM: To study the
      incidence of these echocardiographic risk factors in patients with AFL. MATERIAL
      AND METHODS: We prospectively studied 50 consecutive patients with AFL comparing
      them with two groups of patients with a well known increased risk of
      thromboembolism: 54 patients with AF and 24 patients with sinus rhythm and severe
      mitral stenosis (RSEMS). The group of patients with AFL was also compared with a
      control group of 27 patients with sinus rhythm and no increased risk of
      thromboembolism. In each group, we studied the presence of thrombi and
      spontaneous echo contrast in the left atria and left atrial appendage, emptying
      velocity (Vel A), filling flow (Vel B) and motility of the left atrial appendage
      and left atrial dimensions. RESULTS: When compared with control patients, AFL
      subjects had a higher incidence of spontaneous echo contrast in the left atria
      and left atrial appendage (11 and 42% respectively, p < 0.05); slower flow
      velocity in the left atrial appendage (Vel A 69.25 +/- 25 and 41 +/- 19 cm/s
      respectively, Vel B 55 +/- 16 and 46 +/- 20 cm/s respectively, p < 0.05); lower
      atrial appendage wall motility (4 and 84% respectively, p < 0.001) and a larger
      left atrium (40 +/- 10 and 45 +/- 0.6 mm respectively, p < 0.05). Patients with
      AFL had a lower incidence of echocardiographic abnormalities than subjects with
      AF or RSEMS. Thrombi were found in 2 patients with AFL, 12 patients with AF, 4
      patients with RSEMS and in no control patient. CONCLUSIONS: In AFL, there are
      echocardiographic markers of increased thromboembolic risk in comparison with a
      control group. Nevertheless, the incidence of these factors is lower than in
      patients with AF or with RSEMS.

PMID- 11227242
TI  - [Prevalence of enterohemorrhagic Escherichia coli in a cattle area of Argentina.
      Genotypic characterization of the strains of animal origin].
AB  - BACKGROUND: There is a high prevalence of infection by Enterohemorrhagic
      Escherichia coli (EHEC) and patients with hemolytic uremic syndrome (HUS) in
      Argentina. AIM: To study cattle and pigs as a possible reservoir of EHEC in
      Argentina. MATERIAL AND METHODS: One hundred two healthy animals (68 cattles and
      31 pigs) from a livestock in Argentina, were studied. Stool samples were obtained
      with a rectal swab. The strains were identified by DNA hybridization with
      specific gene probes detecting Shiga-like toxin 1 and 2 (Stx1, Stx2), and hly gen
      related to fimbrial adhesin-associated plasmid. EHEC strains were serogrouped
      using commercial antisera. RESULTS: EHEC was isolated from 30 out of 68 bovines
      cultures (44.1%) and from 25 out of 31 pigs (58.1%). Isolates carrying genes
      codifying both Stx1 and Sxt2, were observed in 50% of cattle and 63.9% of pigs.
      The gene which codifies for hemolysin (associated to fimbrial adhesin) was
      observed in about 41% of EHEC isolates. Strains belonging to serogroups O26,
      O111, and O157 were isolated from cattle, and O111, and O157 from pigs.
      CONCLUSIONS: The high percentage of EHEC in both cattle and pigs and the presence
      of human infection-associated serogroups, suggests that these animals are a
      reservoir of EHEC associated with disease in humans.

PMID- 11227243
TI  - [Toxic epidermal necrolysis. Therapy in ICU with intravenous immunoglobulins in a
      case].
AB  - We report a 27 years old homosexual male with AIDS that was admitted to the ICU
      dehydrated, with fever and severe malaise. He had irregular bullae, an extensive
      purpuric exanthema and a zone of epidermic detachment in the right arm. A toxic
      epidermal necrolysis was diagnosed and therapy with i.v. immunoglobulins was
      started. After four days of treatment, bullous lesions disappeared and the
      extension of exanthema decreased. Toxic epidermal necrolysis is a potentially
      fatal disease and the use of intravenous immunoglobulins for this condition has
      been reported as successful.

PMID- 11227244
TI  - [Bleeding gastric ulcers and acute hepatitis: 2 simultaneous adverse reactions
      due to nimesulide in a case].
AB  - A 66 year-old obese woman with arthrosis, self-medicated with oral nimesulide,
      200 mg daily. After 6 weeks she developed nausea, jaundice and dark urine. Two
      weeks later she had recurrent hematemesis and was hospitalized. Besides obesity
      and anemia her physical examination was unremarkable. An upper GI endoscopy
      revealed 3 acute gastric ulcers and a 4th one in the pyloric channel. Abdominal
      ultrasonogram showed a slightly enlarged liver with diffuse reduction in
      ecogenicity; the gallbladder and biliary tract were normal. Blood tests
      demonstrated a conjugated hyperbilirubinemia (maximal total value: 18.4 mg/dl),
      ALAT 960 U/l, ASAT 850 U/l, GGT 420 U/l, alkaline phosphatases mildly elevated,
      pro-time 49% and albumin 2.7 mg/dl. Serum markers for hepatitis A, B and C
      viruses were negative. ANA, AMA, anti-SmA, were negative. Ceruloplasmin was
      normal. A liver biopsy showed bridging necrosis and other signs of acute toxic
      liver damage. Gastric ulcers healed after conventional treatment and hepatitis
      subsided after 2 months leaving no signs of chronic liver damage. The diagnosis
      of toxic hepatitis due to nimesulide was supported by the time-course of drug
      usage, sex, age, absence of other causes of liver disease, a compatible liver
      biopsy and the improvement after drug withdrawal. Peptic ulcers or toxic
      hepatitis have been previously described as independent adverse reactions in
      patients taking nimesulide or other NSAIDs but their simultaneous occurrence in a
      single patient is a unique event that deserves to be reported.

PMID- 11227245
TI  - [Obesity and fatty acids in the etiology of insulin resistance].
AB  - Fatty acids, obesity and insulin resistance relationship are discussed. In the
      last decades fatty acids (FA) have been implicated in the etiology of insulin
      resistance. Initially, this process was related to FA inhibitory effects on
      glucose uptake mediated by the FA oxidation metabolites. This mechanism known as
      the Randle cycle has been presently discarded based on recent evidence for FA
      effects on glucose metabolism. Now is known that cytosolic lipid content and FA
      molecular structure determines higher or lower storage and oxidation capacity.
      Another factor is given by Tumor Necrosis Factor-alpha, which is overexpressed in
      animal and human obesity, producing insulin signaling and glucose uptake
      inhibition. This paper discuss the role played by FA and obesity on insulin
      resistance, mainly in relation to FA effects on glucose metabolism in the liver,
      muscle and adipose tissues. In the obesity condition adipose tissue releases
      higher levels of free FA which in turn stimulates hepatic glucose production.
      Adipose tissue also, increase TNF-alpha secretion impairing glucose utilization
      and insulin signaling. In muscle, cytosolic lipid content activate a Protein
      Kinase that inhibits the insulin signaling and reduce GLUT-4 translocation. The
      study of cellular and metabolic changes associated to weight gain and its
      relationship with insulin resistance etiology are encouraged.

PMID- 11227246
TI  - [Natural killer cells and the innate immune system in infectious pathology].
AB  - Natural killer (NK) cells form a unique third group of lymphocytes that differs
      from T and B cells in surface phenotype, target cell recognition and function. NK
      cells have two relevant functions, related to the innate immune response against
      pathogens microorganisms. One is cytotoxicity, mediated by the recognition and
      lysis of target cells such as virus and bacteria infected-cells. The second NK
      cell function is to produce cytokines, mainly IFN-gamma, that can modulate innate
      and specific immune responses. Cytotoxicity and cytokine secretion contribute to
      host resistance against microorganisms and both functions are significantly
      altered in infectious diseases.

PMID- 11227247
TI  - [It is time to think about patient's rights. An introduction].
AB  - The underlying purpose of the Hippocratic oath and most medical ethics codes
      dictated during the twentieth century, is patient protection. Nowadays, however,
      clients of health services do not conform themselves with ethical declarations of
      the medical profession but demand that the rights that arise from those
      declarations, become legal instruments that force professionals, health
      authorities and governments to satisfy their health needs and respect their
      individual rights. Probably this is a consequence of the depersonalization of
      medical care, the weakening of ethical bases of physician-patient relationship
      and the emergence of new economical and social philosophies. Now, clients also
      have more expectations and a better knowledge about medicine than in yesteryears.
      Citizen organizations to defend health rights should not be seen as a threaten to
      medical profession and health institutions but as an opportunity to improve
      health care and respect towards people. They should not either harm the mutual
      confidence between the physician and his patient, nor the beneficial spirit of
      medical act, two fundamental components of medical acts.

PMID- 11227248
TI  - [Human rights and their relationship with patient's rights].
AB  - This historical article reviews the most important milestones in the evolution of
      human and patient's rights. The latter have derived from human rights and have
      followed a similar historical evolution, but in markedly different times. This
      has lead to the persistence of monarchic type, paternalistic clinical
      relationship forms in republican societies. The acceptance of informed consent
      and patient's rights has been a democratization of clinical relationships. On the
      other hand the right to body health management is a real cultural revolution. The
      democratization of clinical relationship is in agreement with our technical,
      pluralist and secularized times.

PMID- 11227249
TI  - [About patient's rights].
AB  - This article discusses the difficulties and requirements to accomplish medical
      obligations of veracity, confidentiality, fidelity and respect to intimacy.
      Veracity consists in not saying all what we think but nothing contrary to our
      thoughts. In the fields of terminal care and genetics, conflicts arise between
      the right to veracity and the principles of beneficence and avoiding harm. The so
      called "therapeutic privilege" or the right of physicians to withhold
      information, has been considered among the exceptions to informed consent and is
      rejected by some specialists in ethics. Confidentiality is, for many people, an
      ideal more than a reality, not fulfilled by many physicians in the full sense of
      the word and threatened by third parties. Patients should claim their right to
      confidentiality. The obligation of loyalty or fidelity, that is the obligation
      that physicians have to give priority to patient's needs over own needs, has
      generated divided loyalties in many fields of medical practice due to changes in
      health organization and social context. The right to territorial, body and
      psychological or spiritual intimacy are three aspects of the right to intimacy
      that must be considered. Maybe, patient's rights are just the other face of
      medical obligations towards them. If we physicians become defenders of patient's
      rights, this could be another subtle facet of paternalism.

PMID- 11227250
TI  - [The right to a good quality of health care].
AB  - Quality has a central role in medical care. The satisfaction of the rights of
      people to medical care, presupposes good quality medical acts. The meaning of
      quality goes further than a good attention based on scientific evidence and with
      competent skills. It comprises patient-physician relationship where professional
      behavior is evaluated, based on the fundamental principles of bioethics. These
      principles sustain the measures to control quality of medical actions, to comply
      with the rights of patients to have access to a good professional care.

PMID- 11227251
TI  - [Health research in Chile].
AB  - An analysis of health research in Chile is made, considering factors like
      exaggerated professional training during undergraduate studies and clinical
      residencies, and displacement of professionals from academic activities to more
      remunerative positions. Additionally, the limited role of the Ministry of Health
      in research promotion, evidenced by the almost absent participation of public
      hospitals in clinical research is discussed. Research investment, among a 0.6 to
      0.8% of the GNP, is far from developed countries and Chile has not defined
      relevant health problems where a search effort would have an impact in public
      health. The marked centralism of the country attempts against regional
      application to financed projects. The following suggestions are made: to increase
      the financing for investigation, to reassign resources allowing the access of
      regional institutions, to financing, to discuss in the Chilean Association of
      Medical Faculties (ASOFAMECH) the creation of an academic degree by means of a
      thesis during the professional studies and to give facilities to develop research
      during clinical residencies. Also, the Ministry of Health should be involved,
      creating a national agenda or research priorities and increasing its association
      with Universities. Also training programs for professionals with a special
      interest in investigation should be devised.

PMID- 11227252
TI  - Acute community-acquired pneumonia: current diagnosis and treatment.
AB  - 1. Diagnosis of acute community acquired pneumonia is based on the history,
      physical examination, and chest x-ray.  With respect to diagnosis, the clinician
      should ask, (1) Is the problem pneumonia or something else? (2) Is the pneumonia
      often treated empirically with a macrolide (erythromycin, clarithromycin, or
      azithromycin), a "respiratory quinolone" (levofloxacin, moxifloxacin,
      gatifloxacin, or gemifloxacin) or doxycycline.  4. Concern has expressed that use
      of quinolones as monotherapy for pneumonia may promote the emergence of resistant
      strains.  However, the quinolones are more reliable than the macrolides and
      doxycycline against pneumococcal strains that exhibit reduced susceptibility to
      penicillin G.     5. Appropriate diagnostic studies for patients with moderately
      severe to severe pneumonis include sputum Gram's stain and culture (for those
      patients who expectorate purulent sputum), blood cultures, and acute serum
      sample, and --in some circumstnaces--urinary antigen test for Legionella
      pneumophila. 6. Appropriate initial therapy for patients requiring
      hospitalization includes a third-generation cephalosporin (such as ceftriaxone or
      cefotaxime) plus a macrolide or a quinolone.

PMID- 11227253
TI  - Pharyngitis.

PMID- 11227254
TI  - Common upper respiratory infections in ambulatory practice: otitis media.

PMID- 11227255
TI  - Common respiratory infections: current treatment recommendations.

PMID- 11227256
TI  - Wonder drugs: a history of antibiotics.

PMID- 11227257
TI  - Rhinosinusitis: definition, evaluation and treatment parameters.

PMID- 11227258
TI  - United States life tables, 1998.
AB  - The life tables in this report are current life tables for the United States
      based on age-specific death rates in 1998. Data used to prepare these life tables
      are 1998 final mortality statistics; July 1, 1998, population estimates; and data
      from the Medicare program. Presented are complete life tables by age, race, and
      sex. In 1998 the overall expectation of life at birth was 76.7 years, an increase
      of 0.2 years compared with life expectancy in 1997. Life expectancy increased
      from 1997 to 1998 for each of the four race-sex groups for which life expectancy
      is reported. Life expectancy increased for black males by 0.4 year (from 67.2 to
      67.6), for black females by 0.1 year (from 74.7 to 74.8), for white males by 0.2
      year (from 74.3 to 74.5), and for white females by 0.1 year (from 79.9 to 80.0).

PMID- 11227259
TI  - Long-term variability in the deposition of marine ions at west coast sites in the
      UK Acid Waters Monitoring Network: impacts on surface water chemistry and
      significance for trend determination.
AB  - Eight lake sites in central and south-west Scotland, north-west England and north
      Wales, forming part of the UK Acid Waters Monitoring Network (UKAWMN), have been
      studied with regard to the influence of marine ions on surface water chemistry.
      Since monitoring began in 1988 these sites have exhibited large and long-term
      variation in Cl concentration, which are consistent between regions and can be
      linked to inter-annual variations in wet deposition. Through regression analysis
      against Cl, the response of other solutes to these fluctuations has been
      assessed. Sites show a highly consistent pattern of Na, and Mg retention during
      periods of high Cl, in accordance with the 'sea-salt' mechanism of marine cation
      adsorption onto soil exchange sites following large marine inputs. An associated
      displacement of cations with non-marine sources is also observed, with one or
      more of non-marine Ca, labile Al and hydrogen ions exhibiting a positive
      relationship with Cl at all sites. The relative extent to which these are
      released appears not to follow a simple relationship to site acidity, and may be
      linked to site/region-specific geology and soil characteristics. In addition, an
      inverse relationship between non-marine SO4 and Cl is observed at five of the
      sites, and the possibility is considered that a sea-salt related process, with
      soil retention and subsequent release, may also operate for SO4. A mechanism that
      might explain this process is suggested. The impact of marine inputs on non
      marine solutes, including important indicators of acidification such as pH,
      labile Al and non-marine SO4, has clear implications for the detection of long
      term trends in acidity status and is, therefore, of particular relevance to the
      UKAWMN. Due to their unpredictability, and the long timescale over which they
      operate, fluctuations caused by marine inputs may be difficult to separate from
      acid deposition related long-term trends. Evidence from a longer Cl time series
      from mid-Wales shows that fluctuations in concentration could be linked to the
      North Atlantic Oscillation and might therefore be expected to exhibit a similar,
      decal periodicity. Currently, the UKAWMN dataset only appears long enough to
      represent one climatic cycle. Consequently, and since few surface water chemistry
      datasets in the UK extend over more than a decade, it is important that: (a)
      trend analyses of current data from marine-impacted areas take account of
      possible marine input cycles; and (b) long-term monitoring is maintained into the
      future so that the impact of these cycles can be better quantified, and
      distinguished from anthopogenically-induced long-term changes.

PMID- 11227260
TI  - A model for predicting chloride concentrations in river water in a relatively
      unpolluted catchment in north-east Scotland.
AB  - The River Dee is an oligotrophic soft water system, in the NE of Scotland, with a
      catchment area of approximately 2100 km2. The river rises in the Cairngorm
      Mountains and enters the North Sea at Aberdeen, approximately 140 km from its
      source. Water chemical quality data was collected every 2 weeks over 12 months
      for 59 sites distributed throughout the catchment. River water chloride
      concentrations increased significantly from west to east. In depth investigation
      of the relationship with distance from the coast revealed the significant
      difference in spatial distribution of river water chloride concentrations between
      upland and lowland/agricultural areas, suggesting the possible importance of
      agricultural practices to streamwater chloride concentrations. Thirty of the
      sample sites are independent and have been used to develop a simple model for
      prediction of streamwater Cl- concentration throughout the catchment. The model
      has been validated using data from the remaining sub-catchments. The model shows
      that mean Cl- concentration may be reliably predicted from distance from the
      coast and the percentage of improved grassland and arable land cover in each sub
      catchment (r2 = 0.98). It is postulated that the land use effects may be partly
      due to the evolved link between landuse and catchment altitude characteristics,
      rather than just the direct effect of applied potassium chloride fertiliser on
      agricultural land. It was noted that there was insufficient forestry within the
      River Dee Catchment to reliably include % forest cover in the model.

PMID- 11227261
TI  - Effects of forest cover and topographic factors on TOC and associated metals at
      various scales in western Scotland.
AB  - Studies at the stream catchment scale have yielded inconclusive evidence of the
      effects of forest land use on the concentrations of organic carbon in drainage
      waters. The aim of this paper is to examine the effects of forests on carbon in
      drainage waters at the plot scale by comparing concentrations of total organic
      carbon (TOC) and associated metals in soil solutions from sites under forest and
      moorland vegetation. At an upland site in south-west Scotland soil solution TOC,
      aluminium and iron concentrations varied with land cover. Mean concentrations of
      all three determinands were at least 1.5 times greater under forest than under
      moorland, despite considerable spatial and temporal (seasonal) variability. TOC
      in soil solutions was also found to vary significantly with both relief and
      altitude. The altitude effect was particularly marked, with an increase of 26 mg
      x l(-1) x 100 m(-1) increase in altitude found at an upland site in west-central
      Scotland. There were no differences in chloride, sulphate or base cation
      concentrations between forest and moorland sites. Differences in aluminium
      concentrations could not be linked to atmospheric scavenging at the forest sites,
      but were closely linked to differences in TOC.

PMID- 11227262
TI  - Temporal changes in soil properties at an upland Scottish site between 1956 and
      1997.
AB  - The aim of this study was to examine the frequency with which soil samples
      require to be taken in order to determine significant temporal changes in soil
      properties. The examination was carried out using data from Glensaugh Research
      Station in north-east Scotland where podzolic soils were sampled in 1956, 1977
      and 1997, and by re-analysis of archived material. Significant differences in
      chemistry due to storage were detected, particularly decreases in pH of air-dried
      organic soils. In these cases original data were used for statistical analysis to
      establish changes between 1956 and 1997. Temporal changes were found for
      exchangeable Ca and Mg which generally decreased with time throughout the soil
      profile, whereas exchangeable H increased. Derived data, such as percent base
      saturation, declined dramatically due to decreases in exchangeable base cations.
      Similar podzolic soils were sampled at an adjacent Environmental Change Network
      (ECN) site in 1993. Application of statistical techniques to the ECN soil
      chemistry data allowed an estimation of the detectable change between any two
      years. These data along with the rates of temporal change from 1956 to 1997
      allowed the calculation of the number of years required for measurable changes to
      be achieved. These changes and sampling intervals vary among different horizons
      and chemistries. Although they are site-specific, they do confirm that the
      current ECN protocols of a 5-year and 20-year sampling would be appropriate in
      order to detect changes in soil properties over time at this site.

PMID- 11227263
TI  - Is in-stream processing an important control on spatial changes in carbon fluxes
      in headwater catchments?
AB  - Data on small-scale spatial variations in instantaneous fluxes and concentrations
      of dissolved organic carbon (DOC), dissolved inorganic carbon (DIC) and free
      carbon dioxide (CO2) are presented for a small acidic headwater stream in NE
      Scotland. Chloride is used as a conservative element to estimate additional,
      diffuse inputs of water into the main stem of the stream, other than those from
      tributaries. Downstream changes in instantaneous carbon fluxes were calculated
      and then used to estimate losses and gains of carbon within the stream system.
      Dissolved organic carbon concentrations in the stream ranged from 1.19-6.06 mg l(
      1) at its source to a maximum of 10.0-25.3 mg l(-1) as the stream passed through
      deep peats; DOC concentrations then declined in the lower part of the catchment.
      DIC concentrations were initially low, increased to 1.5-3.0 mg l(-1) and then
      decreased to 0.1-1.65 mg l(-1) at the lowest site. Free CO2 concentrations
      increased from 0.35 mg l(-1) at the stream source to 3.30 mg l(-1) as the stream
      passed through the peat dominated area. Continually high inputs of CO2-rich water
      (> 6.0 mg l(-1)) from tributaries maintained these high concentrations in the
      main stem, until approximately 1.74 km downstream, when there was a rapid decline
      in concentration. Significant changes in DOC, DIC and CO2 fluxes occur over a
      distance of 2.7 km downstream from the stream source to the catchment outlet.
      Between 5.64-41.5 mg C s(-1) as DOC and 2.52-16.2 mg C s(-1) as DIC are removed
      from the water column. Between 6.81 and 19.0 mg C s(-1) as CO2 is lost along the
      stream length as progressive equilibration with the atmosphere occurs. We
      estimate that 11.6-17.6% of the total DOC flux is removed from streamwater by in
      stream processes. Dissolved inorganic carbon (HCO3- and free CO2) losses are in
      excess of nine times its measured flux at the outlet of the catchment. These
      results suggest that in-stream processing of DOC and DIC and outgassing of CO2
      are important controls on the spatial variability of carbon fluxes within
      headwater streams in upland catchments dominated by organic-rich soils.

PMID- 11227265
TI  - The impact of variable snow pack accumulation on a major Scottish water resource.
AB  - In regions such as northern Scotland, where winter temperatures are such that the
      occurrence of snow is borderline under the present climate, potential changes
      affecting precipitation and temperature regimes may have a disproportionately
      large impact on snow processes and hydrological behaviour. The physical
      characteristics of mountainous areas in Scotland mean that the spatial
      variability of snowpack accumulation is high, as well as the temporal variability
      caused by the climate. There have been few modelling studies aimed at assessing
      the significance of snow resources in these areas and none that have adopted a
      spatially distributed approach. This paper describes the approach taken in
      applying a new distributed model to a headwater catchment in the Cairngorm
      Mountains. The results demonstrate the importance of wind on re-distributing snow
      to create deep accumulations in small sheltered pockets. These accumulations are
      shown to be important in sustaining baseflows in the rivers, long after snow has
      melted from the rest of the catchment. The model has also produced a first set of
      maps showing how predicted snow depths vary across the catchment through the
      winter.

PMID- 11227264
TI  - Manganese and land-use in upland catchments in Scotland.
AB  - Manganese (Mn) in surface waters is a micronutrient, but elevated concentrations
      are toxic to fish and impair drinking water quality. In Scotland, undesirable Mn
      concentrations (> 0.05 mg l(-1)) occur predominantly in upland freshwaters
      because the acidic pH and organic nature of catchment soils favour Mn
      mobilisation. The relationship between upland land-use in Scotland and Mn
      concentrations in surface waters is reviewed. Conifer afforestation is associated
      with enhanced Mn in runoff. Mn is leached from conifer foliage and litter, and
      mature conifers enhance acid deposition and loss of Mn from acidified catchment
      soils. After harvesting, increased soil pools of water-soluble Mn and elevated Mn
      concentrations in runoff have been observed. Liming, fertiliser addition,
      drainage ditch construction and ploughing to improve upland pastures, and
      muirburn on grouse moors may also increase Mn concentrations in runoff, but the
      evidence is less clear-cut. The extent to which land-use influences Mn
      concentrations in upland catchments in Scotland is modified by catchment
      hydrology and soil type. Catchment geology, instream processes and standing water
      stratification are probably lesser influences on Mn concentrations in surface
      waters of upland catchments in Scotland. The location of land-use in upland
      catchments, especially in the riparian zone, is critical in determining its
      effect on Mn in runoff. Climate change is expected to increase Mn concentrations
      in runoff from upland catchments in Scotland because of predicted changes in soil
      hydrology.

PMID- 11227266
TI  - Variation in river water temperatures in an upland stream over a 30-year period.
AB  - Stream water temperature data from the Girnock burn, a 30-km2 catchment in
      Scotland were examined for systematic variation across 30 years of record (1968
      1997). The data suggest that there has been no change in mean annual temperature
      with time, but at a seasonal level there is some indication of an increase in
      mean daily maximum temperatures during the winter (December to February) and
      spring (March to May) seasons. For the spring season, there is also evidence that
      mean temperature has increased. There are no apparent or obvious changes in
      stream flow to account for this. The strong relationship between air and stream
      temperatures (r2 = 0.96) implies that changes in the stream are the result of
      changes in the climate. It is possible that this may occur as a result of the
      effect of increasing air temperatures which may have also reduced the influence
      of snow and snowmelt on the catchment during the winter and spring seasons.

PMID- 11227267
TI  - Reducing sediment inputs to Scottish streams: a review of the efficacy of soil
      conservation practices in upland forestry.
AB  - The historical process by which a soil conservation strategy has evolved within
      the UK forestry industry is briefly reviewed. Particular attention is given to
      the development of practical and effective guidelines to prevent both soil damage
      and sediment entering water courses. It is concluded that the 'Forest and Water
      Guidelines', together with other forest industry manuals, largely provide
      adequate protection for aquatic habitats from pre-afforestation cultivation and
      from harvesting activities. The problem of soil erosion owing to ploughing of
      open furrows has largely been obviated by improved drainage network design
      coupled with the use of vegetated buffer strips and sediment catchpits.
      Alternative site preparation techniques, such as 'moling' or 'dolloping' of
      afforestation sites, are now preferred. However, the effects on slope hydrology
      and the improved soil conservation associated with these methods require
      quantifying. Additional understanding of effective buffer strip function, for
      example, on a variety of slope angles, soil types and vegetation associations
      would be beneficial. The design of forest roads and the associated network of
      drains, culverts and sediment catchpits is addressed in forestry guidelines.
      Future potential in this area may involve the use of Geographical Information
      Systems in the effective design of road networks which minimise adverse effects
      on slope hydrology. Similarly computer simulation of flow routing might aid in
      the design of road drain networks. At the more local scale there remains scope
      for further research aimed at minimising soil disturbance by machinery.
      Consideration should also be given to the long-term sustainability of the soil
      structure through second and subsequent crop rotations.

PMID- 11227268
TI  - Modelling instream nitrogen variability in the Dee catchment, NE Scotland.
AB  - The Integrated Nitrogen in CAtchments model (INCA) was applied to the River Dee,
      Aberdeenshire, NE Scotland. To a first approximation the model was able to
      simulate the annual mean streamwater NO3-N concentrations observed along the
      length of the main channel. This provided the basis for using INCA to
      subsequently explore the effects of N deposition and land use management on
      streamwater NO3-N concentrations and loads. On an annual timescale, the model
      predictions suggest that NO3-N concentrations will decrease by 5% following a 20%
      reduction in fertiliser application. Furthermore, model results also suggest that
      a 50% increase in N deposition will cause a 15% increase in the streamwater NO3-N
      concentrations. The utility of INCA as a tool for catchment management is
      discussed, current limitations are highlighted and possible improvements are
      suggested.

PMID- 11227269
TI  - Assessing the effects of land use on temporal change in well water quality in a
      designated nitrate vulnerable zone.
AB  - The nitrate concentration in discharge from the Balmalcolm borehole in Fife,
      Scotland, has steadily increased from 4.5 mg l(-1) NO3-N in the early 1970s to
      11.0 mg l(-1) NO3-N in 1998. Consequently the catchment of the borehole, covering
      an area of 400 ha has recently been designated a Nitrate Vulnerable Zone under
      the EC Nitrate Directive [Commission of European Communities L375, (1991) 1]. The
      sandstone aquifer that supplies the borehole is recharged by water draining from
      land that is intensively cropped to green vegetables. There is, therefore, a need
      to identify appropriate land management techniques that will help to abate the
      nitrate losses from the land and to estimate the length of time that it is likely
      to take before the abatement is observed as a decrease in well-water
      concentrations. Estimates of nitrate leaching for the range of crops that have
      been grown in the catchment over the last 30 years have been made using a balance
      sheet approach, modified to allow for estimates of denitrification and in-field
      composting of vegetable crop residues. Integration over the whole catchment using
      a GIS approach, indicates a steady-state well water [NO3--N] of 23 mg l(-1)--a
      situation that has not yet been reached. Prediction of the time course of change
      in well water quality from 1970 (when intensification began) has been made by
      calculating the travel time from different parts of the catchment both in the
      saturated and unsaturated zones. The results show good agreement between the
      measurements and simulation. Well water [NO3-N] under potential future management
      scenarios have also been investigated using the same approach. The greatest
      reduction in steady-state concentration, to 9 mg l(-1), is achieved for the
      scenario of extensification to spring cereals with moderately fertilised
      grassland. However, the temporal simulations suggest that it would take
      approximately 100 years before 80% of this change is observed in the well-water,
      starting from a concentration of 23 mg l(-1) .

PMID- 11227270
TI  - Hydrogeochemistry of groundwater in coastal wetlands: implications for coastal
      conservation in Scotland.
AB  - Groundwater in a shallow coastal aquifer in north east Scotland was monitored
      over the hydrological year October 1996-September 1997. Groundwater flow from
      inland areas sustained freshwater conditions in a dune-wetland complex of
      conservation importance. In particular, seasonal flooding of the coastal wetlands
      due to water table rise provided important roosting and breeding habitats for
      waterfowl. Hydrogeochemical analysis revealed that groundwater in the shallow
      sand aquifer was circum-neutral, and non-saline, despite being within 50 m of the
      sea and only 1 m above the mean high water mark. Calcium and HCO3 were the
      dominant cation and anion respectively, reflecting weathering processes in the
      aquifer. Use of the geochemical code NETPATH indicated that calcite weathering in
      shell fragments within the sand was the primary source of Ca and alkalinity
      generation. The concentrations of Na and Cl were also important, though these can
      be explained primarily by atmospheric inputs from precipitation. In detail, the
      spatial and temporal variation in groundwater chemistry was remarkably complex
      for what intuitively appeared a simple aquifer system. Temporal variations in
      groundwater chemistry mainly related to the seasonal event of groundwater
      recharge. Thus, the main period of rising groundwater levels resulted in a marked
      dilution of solutes in the aquifer, implying that water storage greatly increased
      in a relatively short period. A period of several weeks appeared to be required
      for dissolution processes to proceed to equilibrium. Spatial variation in
      groundwater chemistry appears to relate to the spatial distribution of
      geochemical processes in different hydrogeological units. Sulphate reduction,
      alkalinity generation and Fe precipitation appear to be locally important
      processes. The chemistry of groundwater maintains the wetland habitat by
      providing freshwater conditions that allow populations of various plant species
      to flourish. The potentially large recharge catchments of coastal wetlands,
      together with increasing pressures in the coastal zone, dictate that pollution
      can threaten the integrity of hydrochemical processes and requires careful
      monitoring if freshwater wetlands are to maintain their conservation importance.

PMID- 11227271
TI  - Trends in stream water quality in Environmental Change Network upland catchments:
      the first 5 years.
AB  - Hydrochemical data from catchment streams at three Environmental Change Network
      (ECN) upland catchments in north-east Scotland, south-east Scotland and northern
      England have been subjected to statistical analysis to separate the components
      due to long-term trend, season and flow. The relative variances due to each are
      presented for pH, Ca, SO4-S, NO3-N, DOC and Cl. Long-term trends have been
      identified with increases in concentration for NO3-N and DOC, decreases in SO4-S
      concentrations, along with short-term seasonal fluctuations. Application of this
      trend technique has allowed the detection of changes and contributed to an
      improved understanding of catchment behaviour.

PMID- 11227272
TI  - Particulate composition and origin of suspended sediment in the R. Don,
      Aberdeenshire, UK.
AB  - Characterising the nature and origin of suspended particulate and colloidal
      matter in surface waters is a necessary first step in determining the role of
      these materials in the transport of pollutants. With this aim in mind, samples of
      suspended sediment were collected from the R. Don, Scotland, and analysed by a
      combination of X-ray diffraction (XRD) and vertically attenuated infrared
      spectroscopy (VATIR). Additionally, the carbon and nitrogen contents of the
      sediment were measured. Samples were collected at eight sites along the river
      from the headwaters to the mouth, twice during periods of base flow, and once
      during a storm. During the base flows, the amount of suspended solids was
      typically no more than 1-10 mg l(-1), whereas the high flow samples contained up
      to 150 mg l(-1). XRD showed that the crystalline component of the high flow
      samples consisted of the clay minerals illite, chlorite, kaolin, hydroxy
      interlayered vermiculite, and a 10/14 A regularly interstratified
      mica/vermiculite. Non-clay components included quartz, feldspars, amphibole and
      goethite. Kaolin progressively increased in relative abundance downstream. The
      clay mineralogy of base flow samples was more or less identical to high flow
      samples but the non-clay components were reduced and, additionally, talc and
      calcite were present. The identification of many of the crystalline components
      was confirmed by VATIR, and amorphous silica was identified, particularly in base
      flow samples. Organic components were identified as wax, protein, and
      humate/fulvate. Proportionally more protein and wax components relative to
      silicates occurred in base flow samples, whereas the humate/fulvate component was
      most clearly identified in samples from the storm. Organic matter contents ranged
      from approximately 24% during base flow to 13% during the storm, whilst the C/N
      ratio showed a progressive decrease downstream, irrespective of flow conditions.
      Both the characteristics of the mineralogy and the organic matter suggested that
      topsoils were the primary source of the suspended sediment in the R. Don.
      However, the presence of talc and calcite were believed to fingerprint ground
      water sources, which together with the in-stream production of diatoms, may have
      accounted for a significant mass fraction of the suspended particulate matter
      during base flows.

PMID- 11227273
TI  - Fine sediment influence on salmonid spawning habitat in a lowland agricultural
      stream: a preliminary assessment.
AB  - Spawning habitat utilized by Atlantic Salmon (Salmo salar) and Sea Trout (Salmo
      trutta) was characterized in a 1.6-km reach of the Newmills Burn, a small, highly
      canalized tributary of the River Don in Aberdeenshire. The Newmills Burn is
      typical of the intensively farmed lower sub-catchments of the major salmon rivers
      on the east coast of Scotland. Such streams have substantial potential in
      providing spawning and juvenile habitat for salmonids, with high redd densities
      resulting in egg deposition rates of > 5 m2. However, in comparison with upland
      spawning tributaries draining less intensively managed catchments, canalization
      and intensive cultivation has seriously degraded the physical characteristics of
      aquatic habitats in many streams. In the Newmills Burn, spawning gravels have a
      relatively high (> 20% by mass) fine sediment (< 2 mm in size) content. The burn
      is characterized by hydraulic conditions that are suitable for salmonid spawning,
      with modal velocities of 0.50-0.65 m s(-1) and depths of 0.20-0.25 m. However,
      infiltration of fine sediments into gravels is rapid during hydrological events
      in the winter months. Thus, complete siltation of open gravel matrices (simulated
      redds) can occur within a week, and probably within a single moderate to large
      storm event. Appreciable, but small, deposition of organic and silt/clay
      particles can also affect spawning gravels. Egg mortalities in redds following
      spawning are variable, but can be as high as 86% in the Newmills Burn. This may
      be related to fine sediment infiltration, reduced permeability of spawning
      gravels and reduced oxygen supply to ova. It appears that the main cause of high
      influx is sediment loads mobilized from intensively managed land. It is suggested
      that fundamental changes to the management of agricultural land is required if
      fish habitats are to be improved and degraded streams are allowed to re
      naturalize. The need for closely focused investigations of the causal
      relationships between fine sediment infiltration and egg survival is stressed.

PMID- 11227274
TI  - Foreword to the special volume: environmental change, land management and water
      quality in Scotland.

PMID- 11227275
TI  - Mine water pollution in Scotland: nature, extent and preventative strategies.
AB  - Scotland was one of the world's first industrialised countries, and has therefore
      also been one of the first countries to experience wholesale post-industrial
      dereliction. Water pollution arising from abandoned mines, particularly abandoned
      coal mines, is second only to sewage as a source of freshwater pollution nation
      wide, and in many coalfield catchments it is the pre-eminent source. Most of the
      pollution is due to net-alkaline ferruginous waters emerging from deep mines.
      Scrutiny of records from 80 deep mine discharges reveals that iron concentrations
      in these waters are only likely to exceed 20 mg/l, and the pH to be below 6.5,
      where the discharge emerges within 0.5 km of the outcrop of the shallowest mined
      seam. The bulk of mature near-outcrop mine water discharges in Scotland have < 50
      mg/l total Fe, and concentrations > 100 mg/l are only likely where a marine bed
      lies within 25 m of the worked seam. Where the nearest marine bed is more than 80
      m above or below the seam, then the total iron will be less than 4 mg/l, and in
      most cases less than 1 mg/l. Net-acidic mine waters are far more rare than net
      alkaline waters in Scotland, and are most commonly associated with unreclaimed
      spoil heaps (bings). Both net-alkaline and net-acidic discharges have detrimental
      effects on the hydrochemistry and biological integrity of receiving waters.
      Scotland has recently pioneered the use of pre-emptive pump-and-treat solutions
      to prevent mine water pollution, and has also experienced the successful
      introduction of passive treatment technology for both abandoned and active
      workings.

PMID- 11227276
TI  - Water quality of Scottish rivers: spatial and temporal trends.
AB  - The Harmonised Monitoring Scheme (HMS) was initiated in 1974 and represents the
      best-organised source of temporal and spatial data describing water quality for
      the major mainland rivers of Scotland, England and Wales. This paper presents the
      first detailed analysis of HMS data for Scotland, and identifies temporal changes
      in water quality from 1974 to 1995. From a concomitant analysis of catchment land
      cover characteristics, water quality indices have been linked with potential
      'drivers' of change, influencing both point and diffuse sources. Nitrate
      concentrations between rivers are highly correlated with the amount of arable
      land, and relationships exist between grassland cover, orthphosphate-P and
      suspended solids concentrations. Similarly, urban catchments are highly
      correlated with ammonium-N, orthophosphate-P and suspended solids. Spatial and
      temporal trends in water quality for the rivers of Scotland are discussed.

PMID- 11227277
TI  - Managing a complex river catchment: a case study on the River Almond.
AB  - The River Almond catchment in the east central belt rates amongst Scotland's most
      polluted rivers. This paper describes how shifting forms of economic development
      in the catchment since the 1860s have affected river quality. A legacy of effects
      from past land uses has combined with the impacts associated with current land
      uses to present a substantial and complex management challenge. It is argued that
      there have been, and still are, scientific, legislative and socio-economic
      constraints on the abilities of managers to respond promptly to changing patterns
      of impacts on the river system. This response lag has tended to increase the
      costs of subsequent remediation, and has consequently supported a downward
      pressure on the quality standards that are considered 'realistic' by river
      managers. Conversely, advances in science, the expansion of regulatory powers and
      resources, and an increase in public interest in the environment has helped to
      clarify the extent of the management problems in the catchment, and allowed major
      advances in some areas of pollution management. In an attempt to overcome some of
      the remaining weaknesses of river management, river managers and interest groups
      have started to form inter-sectoral and multidisciplinary partnerships. The
      success of these new groupings is highly contingent, not so much on the
      competence of their scientific advice, but on the priority given to water
      protection by the land-use decision-makers involved, and the resources they are
      prepared to commit to funding rehabilitation.

PMID- 11227278
TI  - The role of best management practices in alleviating water quality problems
      associated with diffuse pollution.
AB  - This paper introduces the concept of best management practices for the control of
      diffuse pollution. It considers where they are appropriate, and how the concept
      of a best management practice approach differs from the conventional means of
      controlling pollution by regulating each point source, in relation to established
      environmental quality standards and available dilution.

PMID- 11227279
TI  - Water quality in Scotland: the view of the regulator.
AB  - Water quality in Scotland has progressively improved over the past 50 years as
      the environmental damage, which resulted from the industrial revolution, has been
      addressed. This paper provides an overview of current water quality in rivers,
      lochs, estuaries and coastal waters and describes the limited information
      available on groundwater. The main factors affecting water quality are reviewed,
      with sewage, diffuse agricultural pollution, acidification and urban drainage
      identified as the most important. Trends in pollution pressure and levels of
      investment in pollution control have been used to predict the condition of
      Scotland's surface water over the next 10 years. Major improvements are expected.
      However, progress will be slowed by the increased relative importance of diffuse
      sources of pollution, which are less amenable to legislative controls. Future
      changes in environmental monitoring are also expected to move the emphasis away
      from point source pollution. The current freshwater classification schemes are
      based upon a relatively narrow measure of water quality and are expected to
      expand to include a wider range of ecological parameters. This will result in an
      increase in the waters defined as impacted as the effects of other environmental
      pressures are taken into account. Finally the implications of these changes for
      the future management of the aquatic environment are assessed.

PMID- 11227280
TI  - Environmental change, land use and water quality in Scotland: current issues and
      future prospects.
AB  - An outline of both the scientific and management needs facing the future water
      quality issues of Scotland is discussed. The scientific needs are considered in
      terms of monitoring to increase the understanding of hydrochemical processes,
      issues of scaling, and the need for improved modelling under changing
      environmental processes. In terms of the management needs, the requirements
      highlighted relate to improving the ecological quality of Scottish rivers and the
      implementation of integrated river basin management plans.

PMID- 11227281
TI  - Partitioning the variation within the acid neutralizing capacity of surface
      waters in Scotland in relation to land cover, soil and atmospheric depositional
      factors.
AB  - A method of decomposing the variation in the acid neutralizing capacity (ANC) of
      surface waters in Scotland is described. Using national datasets, a series of
      variables relating to 703 catchments across Scotland is divided into three
      components representing (i) land cover, (ii) soil and (iii) atmospheric
      deposition/altitude. Redundancy analysis (RDA) and (partial) redundancy analysis
      are used to quantify the amount of variation in ANC uniquely attributable to each
      of these components, independent of the effects of the others. The variation
      accounted for by covarying combinations of these components is also determined.
      Approximately 55% of the total variation in ANC across the 703 sites is explained
      by the variables representing catchment characteristics and atmospheric
      deposition. Of this, 8.5%, 2.4% and 6.9% are uniquely attributable to the land
      cover, soil and deposition/altitude components, respectively. A further 38% of
      ANC variation is associated with the covariation between components, with 18%
      accounted for by the combination of all three. Approximately 45% of the variation
      in ANC remains unexplained. The results reflect the integrated nature of
      catchment processes and demonstrate, for these data, that it is a combination of
      land cover, soil and deposition and altitude factors which most explain variation
      in freshwater ANC level. The approach offers a tool with which to assess the
      sensitivity of surface waters to acid deposition at a regional scale and provides
      a way of identifying regional differences in catchment response to acid loading.

PMID- 11227282
TI  - Interaction of nitrogen deposition and land use on soil and water quality in
      Scotland: issues of spatial variability and scale.
AB  - Over large areas of the Scottish uplands anthropogenic sulfur (S) deposition is
      declining in response to stringent national and European controls on S emissions.
      At the same time, however, the relative contribution of nitrogenous (N) compounds
      to the total anthropogenic deposition loading has increased. To investigate the
      significance of N deposition on the potential acidification of surface waters,
      national, regional, and catchment databases were developed to assess the
      relationships between N deposition, soil C/N ratios, land use and surface water
      NO3 concentrations. National classification schemes for land use and soils were
      used as only limited empirical data are available at such large spatial scales.
      Data were screened to eliminate areas where N inputs are dominated by non
      atmospheric sources. From these screened datasets, it was apparent that areas
      with the highest risk of N leaching were situated predominantly in the upland
      areas of south-west and west Scotland (areas with low soil C/N ratios). At the
      regional scale, surface-water NO3 concentration in afforested catchments was
      negatively correlated with soil C/N ratios below 20. This relationship was not
      evident in moorland catchments, where NO3 leaching was strongly related to N
      deposition and the loch/catchment ratio, rather than the soil C/N ratio. Temporal
      trends of regional water quality highlighted as increasing loch NO3
      concentrations between 1988 and 1996-1997, presumably reflecting an increase in N
      deposition, enhanced leaching losses from the terrestrial component of the
      catchment, or altered in-lake processes. The hydrochemical records for two
      catchments in NE Scotland (Lochnagar and Allt a Mharcaidh) highlight the
      importance of within catchment process in controlling the nitrogen response
      observed in surface waters. The potential mechanisms through which vegetation and
      soils may modify incoming deposition are discussed.

PMID- 11227283
TI  - The nitrogen composition of streams in upland Scotland: some regional and
      seasonal differences.
AB  - The nitrogen (N) composition of streams draining four upland regions of Scotland
      was compared in samples collected monthly between April 1997 and April 1998.
      Stream samples were analysed for total N (TN), particulate N (PN), nitrate (NO3),
      ammonium (NH4), dissolved organic N (DON) and dissolved organic carbon (DOC).
      Concentrations of TN were small, generally less than 1 mg l(-1) , dominated by
      dissolved forms of N, and varied significantly between upland regions. Nitrate
      accounted for most of the variability in TN; largest concentrations were observed
      in the Southern Uplands and smallest concentrations were observed in the
      Highlands. Nitrate concentrations were positively correlated with the percentage
      cover of improved grasslands and brown forest soils and negatively correlated
      with the percentage cover of peat. Concentrations of DON also varied between
      regions, but to a lesser extent than those of NO3. Largest concentrations
      occurred in SW Scotland and smallest concentrations in the Cairngorms. Although a
      significant positive correlation between DON and DOC was observed, stream water
      DON content was not related to the percentage cover of peat in the catchment, as
      was the case for DOC. The average DOC:DON ratio was narrower for streams in the
      Southern Uplands than for those in the Cairngorms and Highlands. Nitrate and DON
      displayed contrasting seasonal trends; NO3 concentrations were larger in the
      winter while DON concentrations were larger in the summer. Only a small
      proportion, < 8% and < 7%, of TN was PN and NH4, respectively, the majority of N
      was present as either NO3 or DON. Nitrate was the dominant fraction (58-65%) in
      all regions except the Highlands where DON accounted for 57% of TN. However, the
      relative importance of the DON component increased in the summer in all regions.
      This study has demonstrated that the DON fraction is an important component of
      the total N transported by streams from upland catchments in Scotland. Thus,
      assessments of anthropogenic impacts on N losses from upland ecosystems need to
      consider not only the dissolved inorganic species but also DON.

PMID- 11227284
TI  - The environmental context for water quality variation in Scotland.
AB  - The variation in water quality experienced in Scotland reflects differences in
      the physical environment and land management. These differences occur both as a
      result of natural variability, societal development and pollutant inputs. A large
      proportion of the land area of Scotland is upland in nature which is extensively
      managed. Whereas in the lowlands, intensive land management predominates. In
      addition, water quality in the lowland areas in the vicinity of Glasgow and
      Edinburgh is influenced through the legacy of Victorian and latter day industrial
      and urban development. A general introduction to the spatial distribution of
      these facets of Scotland and their relation to water quality is presented.

PMID- 11227285
TI  - Use of continuous water quality records for hydrograph separation and to assess
      short-term variability and extremes in acidity and dissolved carbon dioxide for
      the River Dee, Scotland.
AB  - A combination of continuous (15-min) pH, conductivity and temperature
      measurements and fortnightly spot-sampled water quality data were used to examine
      temporal variability and extremes in river water quality in an upland Scottish
      river: the River Dee at Mar Lodge. An empirical relationship was established for
      Gran-alkalinity by multiple regression against flow and conductivity for the
      fortnightly data. Applying this relationship to the continuous data, an estimate
      of continuous Gran-alkalinity was calculated. The continuous Gran-alkalinity
      record was used as (1) a conservative tracer in a simple two-component mixing
      model to determine the relative proportions of near-surface runoff and deeper
      groundwater contributing to stream flow; (2) to deconvolute the contribution of
      weathering and sea-salt contributions to stream conductivity; and (3) to
      calculate the excess partial pressure of carbon dioxide in stream water. The
      episodic variations in pH, weathering and sea-salt conductivity and excess
      partial pressures of carbon dioxide (EpCO2) associated with high flow events in
      the River Dee suggest that hydrological pathways play an important role in
      determining stream chemistry. The results of the hydrograph separation indicate
      that groundwater provides an important contribution to stream flow, and that
      there are large and hydrologically active stores of groundwater within the upper
      River Dee catchment. Sea-salts have an important influence on stream
      conductivity, particularly with the onset of storm runoff following summer
      drought periods. This suggests that sea-salts are concentrated in the upper soil
      horizons by dry deposition and/or evapotranspiration. EpCO2 behaves non
      conservatively and shows marked diurnal variability under low-flow conditions
      during summer, inducing diurnal pH variations, and indicating the importance of
      within-river biological processes. This study emphasises the very intermittent
      nature of water quality extremes with stream spates and the diurnal nature of
      biologically-induced responses. Fortnightly sampling programmes do not capture
      the range of high flow extremes, and with sampling undertaken during the working
      day, biological extremes occurring at night are also missed, introducing bias.
      This study shows the value of continuous measurements for infilling aspects of
      these intermittent extremes. However, it is also noted that the relatively simple
      patterns of response observed from the continuous measurements may well belie a
      much more varied response at the sub-catchment and hillslope scales, as local
      chemical and hydrological heterogeneities do occur. Thus, the two-component
      mixing model used is, in practice, based on catchment integrated values for a
      range of soil water and groundwater endmembers.

PMID- 11227286
TI  - Alkalinity measurements within natural waters: towards a standardised approach.
AB  - A discussion on the measurement of alkalinity in bicarbonate bearing and acidic
      waters is presented as a move towards developing a standardised approach within
      the aquatic sciences. The discussion is based on theoretical and practical
      considerations. Practical illustrations are provided from measurements of calcium
      bicarbonate bearing waters (River Thames) and acidic to near neutral waters from
      acidic soil systems with calcium bearing groundwater sources (the mid-Wales
      region and the Scottish Dee basin). A comparison of single endpoint and Gran
      procedures is made and the various error terms assessed. It is concluded that
      single endpoint and Gran methodologies are applicable in the standard pH
      titration used in aquatic research (pH 4.5-4.0). However, analytical errors
      increase, particularly for the single endpoint titration, the lower the
      endpoint/endpoint-range in pH. For the Thames, the value of a single endpoint
      over a Gran procedure is illustrated. The Thames results show that some buffering
      components may still be titrated out within the Gran titration range used: this
      leads to an underestimate in the alkalinity. Indeed, by making a comparison
      between single endpoint and Gran alkalinity measurements, the Thames results
      indicated the presence of unexpected buffering components: the interrogative
      nature of this type of analysis is highlighted. A standardised approach is
      outlined.

PMID- 11227287
TI  - [Pathophysiologically oriented therapy of acute pancreatitis].

PMID- 11227288
TI  - [Enteral nutrition in acute pancreatitis].
AB  - The metabolism of acute pancreatitis is characterized by hypermetabolism and
      catabolism. Evidence for glucose intolerance occurs in anywhere from 40 to 90% of
      cases and urine urea nitrogen may increase up to 40 g/day. The most important
      aspect when considering nutritional therapy is determining the severity of the
      pancreatitis. The APACHE-II-scoring-system and the time honored Ranson criteria
      are useful for differentiating severe from mild pancreatitis. Despite some
      limitations in sensitivity and specificity, studies have suggested that patients
      with 2 or less Ranson criteria and an APACHE-II-score of 9 or less have mild
      pancreatitis, while patients with 3 or more Ranson criteria and an APACHE-II
      score of 10 or more have severe pancreatitis. Evidence of organ failure on
      clinical presentation and pancreatic necrosis on dynamic CT scan are also
      important factors in determining severity of pancreatitis and are probably the
      two major indicators of patient outcome. Only 3 prospective randomized controlled
      trials have compared enteral to parenteral nutrition for pancreatitis. All
      studies described successful use of enteral feeding without exacerbating the
      disease process although a mild stimulation of exocrine pancreatic secretion
      could not be prevented, even when the tube was placed below the ligament of
      Treitz. Kalfarentzos [11] and McClave [14] could show that hyperglycemia was
      worse in the parenteral feeding patients compared to the enteral feeding group
      and Windsor [24] concluded with respect to the results of his study, that enteral
      feeding modulates the inflammatory response in acute pancreatitis. Conclusions
      regarding the use of enteral or parenteral nutrition in acute pancreatitis are
      difficult to form, as there is a need of more prospective studies. As ileus may
      be a problem in patients with greater severity of pancreatitis, limiting the
      application of early enteral feeding, the route of nutritional support should be
      determined by the clinical course and the severity of the disease.

PMID- 11227289
TI  - [Possibilities and limits of interventional therapy in necrotizing pancreatitis].
AB  - We present a new technique for minimal invasive radiological assisted
      necrosectomy (MIRAN) for infected necrosis in acute pancreatitis. We describe how
      to place volumic catheters for fragmentation and extraction of necrotic material.
      In addition a new technique is described for minimal invasive occlusion of
      selected pancreas tail to avoid fistulas. In 26 patients with infected necrosis
      of the pancreatic region, 12 patients (46.2%) could be healed by MIRAN alone. 5
      patients (19.2%) could be satisfactory treated with a combination of MIRAN and
      operative necrosectomy. 9 patients (34.6%) died, 5 of them postoperatively. In 7
      cases death followed multiple organ failure/dysfunction syndrome. 12 (71%) of 17
      patients with the aim of curative treatment could be satisfactory treated with
      MIRAN. 2 other patients (12%) received additional surgery, 3 patients died (17%),
      2 of them without any other treatment. The advantages of MIRAN are reduced
      trauma, general anaesthesia is not necessary, no difficult surgical preparation
      is necessary, no limits for additional therapy, reduced damage of neighbouring
      organs and vital pancreatic tissue as well as avoiding splenectomy.

PMID- 11227290
TI  - [Neuroendocrine tumors of the gastrointestinal tract. Prospective analysis of 29
      patients and review of the literature].
AB  - Neuroendocrine tumors are rare and can be observed in different gastrointestinal
      organs. The diagnosis often is made by incidence like in carcinoids of the
      appendix vermiformis, or special clinical symptoms may develop due to tumor
      growth. 29 consecutive patients were evaluated prospectively during 30 months. In
      21 of them, the first diagnosis was obtained after an operative procedure. In 3
      cases, the tumor was found incidentally during another oncological procedure. In
      4 patients, the histological examination of biopsy specimens had shown an
      undifferentiated adenocarcinoma. In 8 of the patients, recurrent surgery was
      necessary because of recurrency of the disease. The mean observation time of all
      patients was 10.6 months. 6 of 29 patients died on disease-related symptoms. The
      results are discussed based on the literature with special regard to organ
      related characteristics of different gastrointestinal neuroendocrine tumors.

PMID- 11227291
TI  - [Prospective randomized study comparing the effectiveness and tolerance of
      various low-molecular-weight heparins in high risk patients].
AB  - INTRODUCTION: In several studies, low-molecular-weight-heparins (LMWH) have been
      shown to be as effective in the prevention of deep vein thrombosis (DVT) as
      unfractionated heparin. However, different LMWHs vary significantly in their
      pharmacokinetic profile and bioavailability pattern. It remains unknown, whether
      these pharmacological differences result in a clinically divergent behavior.
      METHODS: Safety and antithrombotic efficacy of three LMWHs, certoparin (18 mg),
      dalteparin (30 mg) and enoxaparin (24 mg), were compared in a prospective,
      randomized controlled trial involving 188 patients undergoing knee or hip
      replacement or spinal surgery. Efficacy was assessed by changes in venous flow
      patterns between pre- and postoperative Doppler sonography. The clinical endpoint
      for the assessment of safety were intra- and postoperative bleeding, changes in
      activated partial thromboplastin time (APTT) and thrombin clotting time (TCT),
      local hematoma and local infections. RESULTS: Two verified DVTs (1.1%) were
      observed in the study, leading to no statistical difference in the antithrombotic
      efficacy of the used LMWHs. In 21 patients (11.2%) local hematoma or local
      infections complicated the postoperative course. Of these 21 patients, 13
      belonged to the certoparin group, compared to 4 patients each in the other groups
      (p < 0.01). An allergic reaction occurred in only one case treated with
      dalteparin. No differences between the groups were observed in terms of intra-
      and postoperative bleeding, APTT, TCT and blood count. CONCLUSION: The results of
      this study suggest, that all three LMWHs are equally efficacious in the
      prophylaxis of DVT in high risk patients after orthopedic surgery. Larger
      randomized controlled trials are necessary to confirm this conclusion and to
      evaluate the clinical relevance of the observed differences in postoperative
      complications.

PMID- 11227293
TI  - [Pancreatitis and nutrition. Significance of the gastrointestinal tract and
      nutrition for septic complications].
AB  - Septic complications are an important factor for the morbidity and mortality of
      acute pancreatitis. The gut has been identified as a source of infection early in
      the course of the disease allowing intestinal bacteria to translocate into
      pancreatic necrosis and other organs. Bacterial translocation is promoted by an
      impaired intestinal mucosal barrier which can be attributed to the reduced oxygen
      and substrate supply of the intestine during the early systemic response to the
      pancreatic injury. A rat model of severe acute pancreatitis has been used to
      confirm the hypothesis that an impaired mucosal barrier can be stabilized by
      supplying certain nutritients, vitamins and trace elements. Following a
      discussion of the many aspects of bacterial translocation and gut derived sepsis,
      the role of the gut and nutrition for the development of septic complications in
      acute pancreatitis is summarized as follows: Early in the course of acute
      pancreatitis the gut is a target organ of the primary systemic inflammatory
      response (SIRS) to pancreatic injury. SIRS-induced gut barrier dysfunction
      promoting bacterial translocation makes the gut the motor for secondary (septic)
      complications. As a septic focus the gut becomes a target for therapeutic
      measures aimed at stabilizing the impaired gut barrier. Nutritive factors
      demonstrated to improve impaired gut barrier function include early enteral
      feeding and specific factors like glutamine which are essential for enterocytes
      and colonocytes in stress. Experimental data are presented to underline the
      significance of these nutritive factors and subsequent randomized multicenter
      trials performed to verify the positive experimental results are introduced. The
      effect of other nutritive factors (e.g. omega-3-fatty acids) has not yet been
      systemically investigated. Thus, experimental and clinical studies need to be
      performed for evaluating their effect on bacterial translocation and the disease
      course in acute pancreatitis.

PMID- 11227292
TI  - [Significance and incidence of type II heparin-induced thrombocytopenia. A
      prospective study].
AB  - AIM: The incidence of heparin-induced thrombocytopenia (HIT type II) as a
      consequence of postoperative thrombosis prophylaxis after hip or knee prosthesis
      was investigated in this study. Furthermore the platelets count was
      postoperatively analysed in patients without HIT II. PATIENTS AND METHODS:
      Patients with knee and hip prosthesis were included in a prospective study during
      an 8 months period. All patients received 3 x 5,000 Liquemin (Hoffmann-LaRoche)
      from the day of the operation until discharge. In cases with a platelet count
      drop of more than 40% and in patients with clinically manifest thrombosis or
      embolism a HIT type II test was initiated. RESULTS: 5 of 252 patients included in
      this study developed a HIT type II. The platelet count drop was on average 65.7%
      (40.9-81.6). One patient died of a lung embolism (lethality 20%). Four patients
      were treated with Hirudin and 1 patient with Danaproid-Natrium. There was no drop
      of the platelet count between the 5th and 7th postoperative day of more than 15%
      in the other patients without HIT type II. CONCLUSION: In operative departments
      not enough attention is paid to HIT type II. Knowing the risks with an
      appropriate monitoring HIT type II can be early detected. Under these conditions
      the advantages of a heparin prophylaxis outweigh the risk of developing a HIT
      type II with it's life threatening sequelae.

PMID- 11227294
TI  - [Calcifications after operations of the subacromial space].
AB  - OBJECTIVE: Although there are several studies on the development of periarticular
      calcifications after different operation procedures of the joints, such
      calcifications have only seldomly been described in connection with operations in
      the subacromial space. Therefore, the present study was aimed at investigating
      the incidence of periarticular calcifications after operations in the subacromial
      space and to assess their clinical relevance. PATIENTS AND METHODS: In a
      retrospective study we examined 152 patients (51 female, 101 male) who had been
      operated on for primary shoulder impingement by open or arthroscopic procedures.
      The average follow-up time was 32.5 months. The assessment of the outcome of the
      treatment was performed using the criteria of the Constant score, different
      shoulder tests, a visual-analog scale for the evaluation of pain, and by
      evaluation of radiographs. RESULTS: Our study revealed good clinical results in
      the operative treatment of different stages of primary shoulder impingement and
      thus confirmed the results of similar studies before. However, in 25.6% of all
      patients we found periarticular calcifications. Hereby, calcifications occurred
      significantly more often after open procedures (56.8%) than after arthroscopic
      procedures (12.9%). There was non correlation between the occurrence of such
      calcifications and the stage of the disease. Moreover, comparison of the clinical
      results and the Constant scores at follow-up did not reveal any differences
      between patients with and without periarticular calcifications. CONCLUSION: Our
      study shows that the presence of periarticular calcifications after operations in
      the subacromial space is not necessarily associated with clinical symptoms.
      Therefore, routine prophylactic measurements against such calcifications are not
      justified.

PMID- 11227295
TI  - [Results of operative therapy of periprosthetic femur shaft fractures in total
      hip endoprostheses].
AB  - Periprosthetic femoral shaft fracture represents an uncommon but potentially
      devastating complication associated with total hip arthroplasty. The treatment
      should result in complete union of the fracture and at the same time guarantee
      stability of the implant. 15 patients treated between 1992 to 1998 were analysed.
      Clinical and radiographic follow-up averaged 30 months (6-79 months) in 13 cases.
      Two patients died regardless of the fracture. The method of treatment depended on
      the intraoperative stability of the prosthesis and in addition on the fracture
      type (Bethea). In 5 cases of intraoperative stability of the prosthesis plate
      fixation was performed. Plate fixation was complicated by fixation failure
      combined with a recurrent fracture in two cases leading to shift to a long stem
      prosthesis. Ten cases of fractures associated with loose stems were treated with
      a new prosthesis using a long stem system. In these cases an uncomplicated
      healing of the fracture was achieved with adequate stability in radiographic
      examinations. The average Harris score was 70 (26-93). For fractures near the
      femoral stem or in case of implant loosening we recommend the shift to a long
      stem prosthesis. Also in fractures distally from the femoral stem tip we prefer
      now long stem implants rather than plate fixation to avoid large exposure of the
      femoral shaft and resultant complications.

PMID- 11227296
TI  - [Cost analysis of hip and knee prostheses as the basis for cost-benefit
      evaluation].
AB  - INTRODUCTION: The diagnosis-related reimbursement for total hip- and knee
      arthroplasty is often interpreted as a claim for cost reduction and thus
      influences increasingly the surgeon's choice of treatment. With regard to further
      planned budget reductions the following questions arise: Remains quality payable?
      Where are cost savings possible? PATIENTS AND METHODS: Prospective analysis of 21
      patients with primary hip- and 26 with knee arthroplasties to identify all cost
      factors during the hospitalization period including the implantation technique
      and quality improvement measures. RESULTS: Expenses of 18,763.26 DM for hip- and
      18,649.40 DM for knee implants were covered by the diagnosis-related
      reimbursement. Compared to cemented implants, the average total costs of
      cementless prostheses were usually less expensive. CONCLUSION: Although the
      current costs are covered, a further reduction of the diagnosis-related
      reimbursement may result in a loss of quality. The present cost analysis outlines
      a guideline for an individual calculation and assessment of possible saving
      effects.

PMID- 11227298
TI  - [Echinococcus cyst of the right ventricle. Diagnosis and therapy of a rare
      disease picture].
AB  - Cardiac involvement is only found in less than 2% of all patients with
      echinococcosis. The case of a 68-year old woman suffering from a hydatid cyst in
      the wall of the right ventricle is reported. The clinical, radiological,
      serological, and histological findings are demonstrated. Immediate relief from
      the symptoms was accomplished by surgical resection of the cyst without the use
      of a cardio-pulmonary bypass. The problems of correct diagnosis and therapy of
      this rare disease are discussed with reference to literature.

PMID- 11227297
TI  - [Ultrasound diagnosis of sternum fractures].
AB  - AIM: With the present study we wanted to examine the value of ultrasonography in
      the diagnosis of fractures of the sternum. METHOD: Included in this study were 11
      patients with pain in the sternal region and suspected fracture of this area
      according to case history and clinical examination. We exclusively used a 7.5 MHZ
      linear scanner. RESULTS: In all 11 cases the fracture was free of doubts
      diagnosed using ultrasound. A fragment dislocation could be visualized in 10
      cases and 1 case showed a fissure of the sternum. The standard lateral X-ray as
      our reference method confirmed the sonographical diagnosis in all cases.
      CONCLUSIONS: The diagnostical value of ultrasonography of the sternum is at least
      as high as that of standard lateral X-ray. When a hypoechoic area over the
      sternum together with a hematoma, a disruption of the cortical bone or a step in
      the bony outline as a sign for fragment dislocation are found, sternal fracture
      is the definite diagnosis. Ultrasonography is quickly feasible, non-invasive and
      gives sufficient information in these cases without side effects.

PMID- 11227299
TI  - [Blunt trauma in soccer. The initial manifestation of synovial sarcoma].
AB  - Report on a young man, who was operated upon after adequate trauma following the
      diagnosis "organizing haematoma of the adductorial compartment". Surprisingly we
      found intraoperatively tumor suggilations. According to the definition of
      Enneking the surgical procedure was finished as "marginal excision" and the
      patient was referred to an oncological center. After multimodal therapy the
      patient is meanwhile tumor and recurrence free for 5 years. In case of such an
      unexpected diagnosis the importance of paying attention to the criterias of an
      "incisional biopsy" is emphasized. The concept of a "conceived biopsy" is
      explained in preoperatively malignant looking tumors. The outstanding
      responsibility of the surgeon for prognosis (local recurrence) and patients
      quality of life (amputation versus limb salvaging) is elaborated.

PMID- 11227300
TI  - [Surgical therapy of giant tubulovillous adenoma of the duodenum and incidental
      serous cystadenoma of the head of the pancreas].
AB  - A villous giant adenoma of the duodenum was diagnosed in a 56-year-old female
      patient with uncharacteristic upper abdominal discomfort after multiple previous
      laparotomies for various indications. A partial pancreaticoduodenectomy was
      performed as radical oncological procedure since the dignity of the neoplasm was
      uncertain. Histopathologic examination revealed medium-grade cell dysplasia of
      the villous adenoma but an incidental serous cystadenoma of the pancreatic head
      as well. The postoperative course was uneventful. The coincidence of these both
      rare neoplastic entities has yet not been described in the literature. The
      surgical options for treatment of both neoplasms are discussed.

PMID- 11227301
TI  - [Hemodynamic effects of pneumoperitoneum in lithotomy position].
AB  - AIM OF STUDY: The study investigates the haemodynamic effects of the varying
      intraabdominal pressures and patient positions during gynecological procedures
      employing pneumoperitoneum in lithotomy positions. METHODS: TEE was used to
      determine end-diastolic and end-systolic left ventricular surface areas and
      ejection fractions were calculated from these data. To evaluate intraabdominal
      volume shifts the diameter of the internal iliac vein was measured by mean of
      vaginal ultrasound. RESULTS: In the horizontal lithotomy position both LVEDA and
      LVESA increased when intraabdominal pressure increased by 10 and 15 mmHg,
      respectively. LVAEF significantly decreased when intraabdominal pressure
      increased by 15 mmHg. Also DVII decreased. In Trendelenburg position there was no
      change in LVEDA, LVESA, LVAEF and DVII. In Anti-Trendelenburg position LVEDA and
      LVESA decreased. However, LVAEF remained constant and DVII increased. CONCLUSION:
      The increase of the intraabdominal pressure in the lithotomy position results in
      an increase in intrathoracic volume and an decrease in LVAEF via elevation of the
      the lower extremities and compression of the splanchnic vessels. There are no
      changes in Trendelenburg position. However, in Anti-Trendelenburg position,
      gravity results in a decrease in intrathoracic blood volume. In the decreased,
      dilatated heart the increase in intrathoracic volume may increase myocardial wall
      tension and hence oxygen demand, ultimately leading to an acute heart failure. As
      a result laparoscopic procedures in horizontal lithotomy position should be
      avoided in patients with dilatative cardiomyopathy.

PMID- 11227302
TI  - [Basic principles of infected bone and soft tissue surgery].

PMID- 11227303
TI  - [2001--a year of challenging abbreviations].

PMID- 11227304
TI  - [Prion diseases].

PMID- 11227305
TI  - [Hygiene status of ambulances and equipment in rescue services].
AB  - PURPOSE: Focus on hygienic management in ambulances is presented based on
      findings from hygienic microbiological sampling. METHODS: In 44 ambulances, the
      handwashing area, equipment for artificial respiration, insufflation, intubation,
      aspiration, intravasal catheterisation, blood-pressure measurement, and sterile
      materials storage were examined hygienically and microbiologically using the
      following methods: water sampling, imprint technique, and swab technique with
      subsequent cultivation on blood-, endo-, and Sabouraud agar. RESULTS: The highest
      contamination was found in the hand-washing area and on insufflation equipment
      (up to > or = 100,000 cfu/ml), where proof of the potential pathogens
      Pseudomonas, Acinetobacter, and Alcaligenes spp. was found. The second highest
      contamination level was found on the sphygmomanometer cuffs, stethoscopes, and
      respirator masks (e.g., Enterococci and S. aureus were identified). Apparently,
      the germs chiefly originate from the drinking water at the handwashing station,
      from the environment and mucous membranes from the skin, and intestines of the
      ambulance personnel. The predominant hygienic deficiensies were found in the
      equipment of the handwashing areas, and in the storage of resuscitation equipment
      and sterile materials. CONCLUSIONS: Based on the results of hygienic
      microbiological analysis, the main focus of hygienic measures--besides hand
      disinfection--should be on spray disinfection of the sphygmomanometer cuffs and
      stethoscopes as well as disinfection of ambulance equipment and storage areas for
      sterile devices, supplemented by dust protection of ready-to-use materials and
      devices. Stationary dispensers for hand disinfection possessing at least
      midlength levers must become the standard in ambulances, and conventional
      handwashing basins with plastic drinking-water containers and pump must be
      eliminated entirely.

PMID- 11227306
TI  - [The in vivo molecular weight and renal threshold of hydroxyethyl starch in the
      example of molar substituted HES70/0/5].
AB  - The intravascular changes of the in vivo molecular weight of HES 70/0.5 were
      investigated on healthy volunteers. A repeated daily infusion of 835 ml of 6% HES
      solution (50 g HES 70/0.5; Rheohes) during four hours on five consecutive days
      was performed. The analysis of the distribution of the molecular masses in serum
      and urine was performed by SEC-HPLC with MALLS/RI detection. The in vivo average
      molecular weight (Mw) of HES was found to be 58,000 Da at the end of the
      infusion. This was lower than the Mw of 66,000 Da as measured initially in the
      HES solution. In the time following the infusion Mw increased steadily up to
      64,000 Da because of renal elimination of low molecular HES. However, in the
      morning before the start of the next infusion of HES, the average molecular
      weight Mw of HES was even higher up to 71,000 Da. In the first collected portion
      of urine (i.e. up to 8 h after beginning the infusion) the average molecular
      weight of HES was as low as 17,000 Da. During the next hours (i.e. in the second
      collection period lasting from 8 up to 24 h after start of the HES infusion) Mw
      of HES increased up to 28,000 Da. The top fraction of the first period showed
      molecular masses of 27,000 Da, in the second collection period top fraction of
      molecular masses measured 40,000 Da. According to the presented data it is
      concluded that the renal threshold for medium substituted HES is independent of
      the initial Mw and related primarily to the molar substitution of the HES used.
      This renal threshold for medium substituted HES is determined to be at 40,000 Da.
      The in vivo Mw of HES is variable and related to the sampling time and predicted
      predominantly by the molar substitution of the HES used. The in vivo Mw,
      therefore, is not suited for characterisation of HES.

PMID- 11227307
TI  - [Pain relief and anesthesia in obstetrics].

PMID- 11227308
TI  - [Physiological changes during pregnancy relevant to anesthesia].
AB  - Hormone production from the corpus luteum and the placenta as well as the
      mechanical effects of the growing uterus are the main reasons for the
      physiological changes of pregnancy. These have relevant effects particularly on
      the cardiovascular system, the respiratory tract and the gastrointestinal system
      as well as the kidneys and urinary tract. Elective procedures on women of
      childbearing age should only be performed when early pregnancy has been excluded
      as the effects of even the latest anaesthetics at the time of organogenesis may
      not be fully understood. The aim of close teamwork between midwives,
      obstetricians, neonatologists and anaesthetists should be to prevent any
      complications for the mother and to give the newborn the most optimal start in
      it's young life.

PMID- 11227309
TI  - [10 years experience with extracorporeal membrane oxygenation].
AB  - OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) is a supportive therapy
      used for severe acute respiratory distress syndrome (ARDS). We present outcome,
      clinical parameters, and complications in a cohort of 245 ARDS patients of whom
      62 were treated with ECMO. METHODS: Data of all ARDS patients were prospectively
      collected between 1991 and 1999. Outcome and clinical parameters of patients
      treated with and without ECMO were evaluated. RESULTS: Hundred-thirty-eight
      patients were referred from other hospitals, 107 were primarily located in our
      hospital. About one fourth of these patients was treated with ECMO. The survival
      rate was 55% in ECMO patients and 61% in non-ECMO patients. ECMO resulted in very
      few complications, one of them was fatal. No parameter before or during ECMO
      could be used to predict the individual prognosis. CONCLUSION: ECMO is a
      therapeutic option for patients with severe ARDS, likely to increase survival.
      However, a randomized controlled study proving its benefit is still awaited.
      Until the development of a causal or otherwise superior therapy ECMO should be
      used in selected patients.

PMID- 11227310
TI  - [What doe the obstetrician expect of the anesthetist?].
AB  - The obstetrician's expectations of anaesthetists are high and include a high
      level of competence at a specialist level, experience of the delivery room, a
      calm but fast and ordered way of working, a tactful and enquiring approach and
      the ability to work in an interdisciplinary environment. In the area of
      organisation the obstetrician and the anaesthetist should, through optimal
      cooperation, have a good understanding of the procedural plan to ensure the
      safety of mother and child. This includes working in close proximity, regular
      joint consultations and early preinterventional contact with the pregnant patient
      in order to inform them of the anaesthetic options and their inherent risks.
      Despite the undoubted successes resulting from the cooperation between
      obstetricians and anaesthetists, as shown by the reduction in mother and child
      mortality rates, the current structured and medical circumstances are not optimal
      and should motivate both disciplines towards improved joint care.

PMID- 11227311
TI  - [What does the anesthetist expect from the obstetrician?].
AB  - The anaesthetist would ideally like the following to be observed in a timely
      order in the antenatal phase: 1. early provision of information to the patient
      regarding epidural catheter for pain relief in labour, 2. informing the
      anaesthetist about relevant points in the patient history and examination
      findings, 3. knowledge of the contraindications to lumbar regional anaesthesia,
      4. clear information as to the urgency of a caesarian section, 5. provision of
      aspiration prophylaxis. In the intrapartum phase it is necessary through clear
      communication to agree early on: 1. monitoring instructions for epidurals in the
      delivery room, 2. instructions for epidural top ups, 3. whether the presence of
      relatives in theatre in the case of a caesarian section is appropriate. In the
      postnatal phase anaesthetists expect to be actively involved in the resuscitation
      of newborns to fulfill educational requirements, to have clear decisions about
      responsibilities for monitoring of patients post caesarian sections and detailed
      information about early symptoms of possible complications of lumbar regional
      anaesthesia.

PMID- 11227312
TI  - [Pain relief for vaginal delivery--an overview].
AB  - The multimodal aspects of labour pain, it's origin and effects, as well as the
      possibilities of it's treatment will be described from the obstetrician's point
      of view. This will include a comparison of methods in current common use during
      delivery including psychosomatic methods, physical methods, acupuncture,
      homeopathy, use of water, drug therapy as well as the use of local and regional
      anaesthesia. For particular discussion is the use of epidural catheter in
      delivery, with respect to availability, optimal timing and obtaining informed
      consent and it's documentation, as well as teamwork and clear interdisciplinary
      decisions concerning frequency and parameters of monitoring for epidural catheter
      anaesthesia following the motto: "how much is necessary, how little is possible?"

PMID- 11227313
TI  - [Anesthesia techniques for cesarean section--catheter-peridural anesthesia].

PMID- 11227314
TI  - [Spinal anesthesia for cesarean section].
AB  - In the community hospital of Konstanz, spinal block is the standard method of
      anaesthesia for caesarean section. The report below gives a review about the
      advantages of the method compared to other central blocks and describes the
      procedure in detail. The block is performed in the lateral decubitus position by
      paramedian approach, using 0.5% hyperbaric bupivacaine in doses of 10-12.5 mg.
      For postoperative analgesia, morphine 1 microgram/kg BW is added. The spinal
      puncture is carried out with 27-gg-pencilpoint needle which is inserted through
      an introducer. If necessary, cafedrine is employed for support of blood pressure.

PMID- 11227315
TI  - [Analgesia, anesthesia and newborns].
AB  - It should be remembered that almost any drug given during labour may have
      negative effects on the child. On the other hand withholding a drug that is
      otherwise indicated may carry as many risks as giving an overdose or failure to
      treat at the appropriate time. In addition drug therapy may affect the child
      indirectly, for example by reducing placental function. During general
      anaesthesia, the interval between induction and cutting the umbilical cord
      determines the degree of drug load for the child. The interval should ideally be
      between 3-15 minutes. In addition the effect of drugs on the fetus depends on
      many additional factors such as gestational age, plasma binding of the drug and
      amount of fat.

PMID- 11227316
TI  - [Severe multiorgan failure caused by aspiration with laryngeal mask airway].
AB  - We report a case of a 77-year-old woman who developed severe multiple organ
      failure after aspiration with the LMA during ureteral splinting. Two hours after
      induction of anaesthesia the urologists decided for nephrostomy in prone
      position. Therefore the patient was intubated. During removal of the LMA bilious
      secretion was recognized inside the LMA and in the pharynx. Endotracheal suction
      and immediate bronchoscopy showed severe aspiration. After the operation the
      patient was submitted to the ICU. She developed a severe multiple organ failure
      within 12 hours. Recovery took 54 days. The discussion is focussed on risk
      factors for the use of the LMA, adequate intraoperative monitoring, possible
      disadvantages of the applied anaesthetic technique and initial treatment after
      aspiration.

PMID- 11227318
TI  - [not app].

PMID- 11227317
TI  - [Overview of the 43rd Kasseler Symposium. "OR management--demands and
      perspectives"].

PMID- 11227319
TI  - [The measurement of anxiety through computerized content analysis--automation of
      the Gottschalk-Gleser Test].
AB  - The Gottschalk-Gleser Content analysis for the measurement of anxiety and
      hostility has proven to be a valid and reliable content analytic method for the
      quantification of affects in many studies. It was used world-wide, German scales
      have been available since 1980. Especially in the field of psychosomatic medicine
      a lot of research was done. The certain use of this method, however, needs an
      extensive training and the application takes an enormous amount of time. For
      these reasons a computer program for the Gottschalk-Gleser analysis was developed
      in English language, whereas for German texts such a program has not been
      available up to this date. This report describes the development of a computer
      based anxiety measurement method in German--the Dresden Anxiety Dictionary
      (Dresdner Angstworterbuch, DAW). The DAW is designed as a category system for use
      with different content analytic software. The test of reliability and validity,
      using 160 clinical texts, shows that the DAW is a reliable and valid method that
      can be used in different fields.

PMID- 11227320
TI  - ["I dreamed that I dreamed": some notes on the clinical evaluation of therapist
      interventions, exemplified by Deserno's case study (session 290)].
AB  - In No. 8, 48th year, August 1998, of the journal "Psychotherapie--Psychosomatik-
      Medizinische Psychologie" the tape recorder transcription of the 290th session of
      a long-term analysis was studied by three methods (BIP, Frames, ZBKT). The paper
      presented here was stimulated by this publication. From the author's viewpoint
      substantial clinical aspects of evaluation could be added by applying a clinical
      evaluation method developed by R. Langs and his corresponding concept of
      interpretation. Clinical vignettes exemplify the possibility to resolve
      pathological countertransference by using this evaluation method. With the help
      of this method the presented transcription of the 290th session is evaluated
      partially.

PMID- 11227321
TI  - [The effects of psychotherapy on Crohn's disease patients--results of a
      randomized multicenter study].
AB  - In a prospective multicenter study of Crohn disease patients, the influence of
      psychotherapy on the course of the disease and on psychosocial variables
      (anxiety, depression, life satisfaction and data of the PSKB) was studied.
      Psychodynamic oriented psychotherapy was provided in addition to a standardized
      medical treatment and took place during the first year of the two-year
      observation period. 108 of 488 patients were recruited and randomly assigned to
      the psychotherapy and the control group. 84 patients completed the somatic and 81
      the psychosocial follow up. 23% of the control group and 30% of the psychotherapy
      group showed episode-free courses, 29% and 17% respectively underwent surgery
      (worst outcome group). The ranking and comparisons of the disease course showed
      no significant difference (p = 0.125) between psychotherapy and control group.
      The psychosocial variables also showed no differences between these groups.
      Subjectively, the patients report favourable effects to psychotherapy.

PMID- 11227322
TI  - [The validity of the Hornheide questionnaire for psychosocial support in skin
      tumor patients: a survey in an Austrian and German outpatient population with
      melanoma].
AB  - Tumour patients are subject to different degrees of psychosocial distress
      depending on the course of disease, personality variables and amount of social
      support available. Often patients do not spontaneously talk about their distress
      and attending physicians fail to detect it. Therefore, it is important that the
      presence of distress is ascertained by specific screening instruments so that
      appropriate supportive measures can be instituted. The Hornheide Questionnaire
      (HQ) employed for investigating the need for psychosocial support in the case of
      patients with skin tumours and with tumours in the head and neck region
      represents such a specific screening instrument. The present study investigates
      the validity of the HQ on the basis of two representative samples from two
      different University Clinics for treatment and follow-ups of melanoma patients.
      With the help of the HQ, 215 patients at the Dermatology Out-patient Unit of the
      University of Innsbruck and 223 patients at the University of Freiburg were
      investigated with regard to their subjective experience of distress. The external
      constructive validity criteria were established on the basis of the Freiburg
      Questionnaire of Disease-Coping, the questionnaire of social support and Beck's
      Depression Inventory. There were significant differences between individuals in
      the severity of distress in different age groups and in patients in different
      tumour stages. The internal consistency of the HQ and its subscales proved to be
      satisfactory demarcation from other psychosocial dimensions and an adequate
      correlation with similar dimensions (depression, depressive illness coping,
      social support, compliance). The HQ appears to be an economical and valid
      screening instrument for detecting the need for psychosocial support in melanoma
      patients in the out-patient follow-up stage.

PMID- 11227323
TI  - [Primary health care and the consequences of a strategy of denial: inefficient
      and uneconomical management of health problems due to a far-reaching omission of
      clients' world view, self image and psyche from the context of therapy].
AB  - In spite of high prevalence rates, non-somatic health problems remain largely
      neglected in Third World First line health services. Deficits in staff
      qualification and motivation, clients' lack of readiness to perceive their
      problems as psychogenic, and "superstitious" beliefs as to their causation,
      material constraints, and the inapplicability of Western psychotherapeutic
      techniques in non-Western cultures are quoted as possible explanations. We assess
      their validity and potential consequences for the quality of service delivery; a
      different approach towards the training of staff, aiming at the integration of
      attention to psychological problems into everyday service provision, is
      discussed.

PMID- 11227324
TI  - Inflammatory pathways between placenta and foetus.
AB  - Recent evidence indicates that intra-amniotic endotoxin (LPS) and interleukin-1
      alpha (IL-1alpha) accelerate foetal lung maturity and protect from respiratory
      distress syndrome (RDS) more effectively than does antenatal glucocorticoid.
      Inflammatory cytokines promote development of chronic lung disease in the
      premature, acute RDS (ARDS) in children and adults. Systemic exposure to LPS or
      cytokines can result in generalized multiorgan damage. The abnormal host defence
      in the foetus and the premature newborn need to be considered in therapeutic
      interventions.

PMID- 11227326
TI  - Aflatoxin and kwashiorkor.

PMID- 11227325
TI  - Further views by the Erice working group on mother-to-child transmission of HIV
      type 1.

PMID- 11227327
TI  - Mucosal pathology of the foregut associated with food allergy and recurrent
      abdominal pains in children.
AB  - To determine whether children with recurrent abdominal pain (RAP) include an
      excess of children with food allergy (FA), this study examined a consecutive
      series of 84 children (43M, 41F, mean age 7.9 y, range 1.6-15 y) referred during
      1 y to 2 university hospitals. In addition to a clinical examination, the
      patients underwent gastroduodenoscopy with three biopsy specimens, skin-prick and
      patch tests, and comprehensive laboratory tests for atopic allergy. Based on an
      open elimination-challenge test, a total of 28 (33%) subjects were diagnosed for
      FA. In the whole material, specific endoscopic abnormalities were found in 38
      (45%) subjects: oesophagitis in 17, gastric erosions in 8, lymphonodular
      duodenitis in 12 and erosive duodenitis in 5. FA showed a close relationship with
      duodenal lesions, but no significant association with oesophagitis and gastritis.
      The histological findings were mild, although some alterations could be observed
      in up to 66 (79%) subjects, equally often in patients with and without FA. None
      showed villous atrophy or severe infiltration of eosinophilic or mononuclear
      cells. Slightly increased densities of eosinophilic cells were significantly
      associated with endoscopic findings, especially oesophagitis. At least one
      positive skin-prick test with food allergens was found in 11 subjects and a
      positive patch test in 21 subjects, but neither showed an association with the
      endoscopic or histological findings, or even with clinical FA. CONCLUSION: Since
      the children with FA showed significantly more often concomitant mucosal
      pathology of the foregut than those without FA, FA may be considered one of the
      major factors underlying RAP. The report suggests the trial of an elimination
      diet in cases with RAP if lymphonodular hyperplasia or duodenitis is seen on
      gastroduodenoscopy.

PMID- 11227328
TI  - Spontaneous speech at 6 1/2 years of age in children who required neonatal
      intensive care in 1986-1989.
AB  - Spontaneous speech at 6 1/2 y of age was studied in a follow-up of 230 children
      born in 1986-89 who had required neonatal intensive care (NIC) and 71 fullterm
      neonatally healthy control children. Eight aspects of spontaneous speech were
      examined: Information, speech motor function, sound pattern, word finding, word
      selection, grammar, interaction and motivation. The results were analysed in
      relation to gestational age groups (group I, 23-31 wk; subgroup IA, 23-27 wk; IB,
      28-31 wk; group II, 32-36 wk; group III, >36 wk) and a separate group of children
      with congenital malformations (IWCM). Between 66.7% (group IA) and 55.7% (group
      III) had no obvious deviations in any aspect of spontaneous speech compared with
      80.3% of controls. Children born at <32 wk of gestation (group I) had few
      pronounced deviations in speech motor function or formal aspects of spontaneous
      speech. No ability, or hardly any ability, in an aspect of spontaneous speech was
      only found in children born at >32 wk. Deviations in prosody and poor facial
      expressions accompanying spontaneous speech were more common in group I than in
      controls. CONCLUSION: Most children who needed intensive care neonatally had well
      developed spontaneous speech.

PMID- 11227329
TI  - Recurrent abdominal pain, food allergy and endoscopy.
AB  - Gastrointestinal food allergy, a well-recognized clinical entity, has a wide
      spectrum of clinical features, including cutaneous, respiratory and
      gastrointestinal symptoms and objective abnormalities. The gastrointestinal
      alterations in food allergy have been described throughout the gastrointestinal
      tract. Recurrent abdominal pain (RAP) is a common complaint in school-age
      children. The findings among children with RAP of an underlying food allergy
      associated with mucosal pathology of the foregut may support a causal
      relationship between food allergy and RAP. Further studies are needed to
      elucidate whether well-documented food allergy (based on double-blind placebo
      controlled food challenges) is a major cause of RAP.

PMID- 11227330
TI  - Epilepsy in a representative series of Rett syndrome.
AB  - In a representative series of 53 females with Rett syndrome (RS), aged 5-55 y, a
      history of epilepsy was present in 50 (94%), 45 of whom had 5-y active epilepsy.
      Compared with severe mental retardation in general, the median age of seizure
      onset was significantly later (4 vs 0.8 y) and partial complex seizures were more
      frequent (54% vs 23%). Neonatal seizures had occurred in only one and infantile
      spasms in none compared with 26% and 12%. After teenage, the severity of epilepsy
      tended to decrease, i.e. lower seizure frequency and relatively more partial
      seizures. The rate of being seizure-free for 1 y was 8% after 10 y and 40% after
      27 y of epilepsy duration. Frequent seizures were associated with smaller head
      circumference. CONCLUSION: This epilepsy profile could fit in with present-day
      knowledge of RS as a form of dendrito-synaptogenic developmental failure with
      mainly late postnatal consequences, as well as being a relatively stationary
      condition in adulthood.

PMID- 11227331
TI  - Incidence rate of recurrent Kawasaki disease and related risk factors: from the
      results of nationwide surveys of Kawasaki disease in Japan.
AB  - To investigate the incidence of recurrent Kawasaki disease, and to discuss some
      of the potential risk factors, data of the 13th and 14th nationwide surveys of
      Kawasaki disease in Japan were analyzed. To calculate the rate of recurrence,
      10679 patients with 31501.9 person-years were observed. The mean observation
      period was 2.95 y. The rate of recurrence was 6.89 per 1000 person-years, with a
      high incidence within the 12 mo following the first episode. CONCLUSION: The
      incidence was high among those under 3 y of age and those with cardiac sequelae
      during the first episode. None of the other factors affected the incidence.

PMID- 11227332
TI  - The Paediatric Asthma Caregiver's Quality of Life Questionnaire in Swedish
      parents.
AB  - With the Paediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ),
      parents grade impaired activities (5 items) and emotional concern (8 items) from
      1 to 7 regarding how much their own quality of life (QoL) has been affected by
      the disease of their child during the last week. The questionnaire was translated
      into Swedish. To test the feasibility and validity of the Swedish version, 71
      asthmatic children and their families were approached. Sixty-one families (86%)
      participated. The mean age of the children was 8.7 y. Parental grading of
      symptoms (Spearman's rho = 0.637, p < 0.001), the asthma-specific QoL of the
      child (rho = 0.359, p = 0.002) and gradings of asthma from medical records (mild
      asthma median score 6.69, moderate 6.27 and severe 5.12, p = 0.001) were all
      related to overall PACQLQ scores. The sex of the child, the presence of other
      diseases related to allergy, peak flow rate (PEFR) and socio-economic level did
      not affect the scores. Lower scores in the emotional domain were seen in parents
      of children on steroids (p = 0.049). The distribution of scores was heavily
      skewed towards the positive end of the scale, leading to limited power to
      discriminate among parents of children with mild asthma. The instrument had good
      internal consistency and was well accepted by the parents.

PMID- 11227333
TI  - Growth hormone in short children: medically appropriate treatment.
AB  - Bolt and Mul argue persuasively against the "disease" approach and the "client"
      approach in addressing the question of whether growth hormone for short children
      properly belongs in the medical realm. Their own preferred approach, the
      "suffering" approach, is superior to the others but has practical problems that
      would arise in its application. An additional ethical issue, not addressed by
      Bolt and Mul, relates to justice in providing access for children from families
      of limited financial means to growth hormone treatment.

PMID- 11227334
TI  - Breastfeeding duration and previous breastfeeding experience.
AB  - The aim of this study was to examine the effect of duration of earlier
      breastfeeding on the duration of breastfeeding with subsequent births. Medical
      records of 327 women who had had at least two deliveries were analysed; 89 of
      these women had had three deliveries. The average duration of breastfeeding
      increased from 6.01 mo to 6.85 mo with the second baby, but did not increase
      significantly with the third. A significant negative correlation was found
      between duration of first breastfeeding and change of breastfeeding duration at
      the second breastfeeding. Mothers who breastfed their first child for 0-7 mo
      significantly increased the duration of breastfeeding with the second child,
      whereas mothers who breastfed their firstborn for 8 mo or longer significantly
      reduced breastfeeding with the second baby. CONCLUSION: Results support earlier
      studies showing that duration of breastfeeding of the second child is
      significantly related to previous breastfeeding experience. Results also suggest
      that previous breastfeeding experience may lead mothers to regulate duration of
      subsequent breastfeeding toward a level that is optimal for them. The results are
      interpreted with respect to societal changes in breastfeeding patterns, as well
      as the role of maternal learning in breastfeeding behaviour.

PMID- 11227335
TI  - Maternal cannabis use in the sudden death syndrome.
AB  - The smoking of cannabis and tobacco is common in many countries. In contrast to
      tobacco, which is an established risk factor for the sudden infant death syndrome
      (SIDS), nothing is known about cannabis and its effects on SIDS risk. We analysed
      data collected in a nation-wide case control study in New Zealand (393 cases,
      1592 controls) to determine if there is any association between maternal cannabis
      use and SIDS risk. Adjusting for ethnicity and maternal tobacco use, the SIDS
      odds ratio for >weekly maternal cannabis use since the infant's birth was 2.23
      (95% CI = 1.39, 3.57) compared to non-users; and the multivariate odds ratio was
      1.55 (95% CI = 0.87, 2.75). We conclude that frequent maternal cannabis use may
      be a weak risk factor for SIDS, but this finding requires further research.

PMID- 11227336
TI  - Socio-demographic risk factors for home-type injuries in Swedish infants and
      toddlers.
AB  - In this paper we use data from Swedish national registers to study socio
      demographic patterns of hospital admissions as a result of injuries sustained at
      home (poisoning, falls, scalding and ingestion/intrusion of foreign objects) in
      children 0-3 y. The study population comprised 546 336 children born in Sweden
      during the period 1987-91. The different injury mechanisms peaked at different
      ages: ingestion of foreign objects at 10-12 mo, scald injuries at 13-15 mo, non
      drug poisoning at 16-18 mo and drug poisoning at 24-30 mo. In a multivariate
      analysis it was demonstrated that children of young mothers (<24 y) were more
      likely to have been admitted to hospital because of fall injuries and poisonings,
      while children with more than two siblings had a slightly increased risk for all
      injuries. Children of mothers born in a non-western country were more likely to
      have been admitted to hospital because of scald injuries; odds ratio (OR) 1.7
      (95% CI: 1.4-2.1), while they were less likely to have been admitted because of
      fall injuries; OR 0.8 (0.7-0.8) and non-drug poisoning; OR 0.5 (0.4-0.6).
      Children in families who received social welfare benefits were more likely to
      have been admitted to hospital because of fall injuries; OR 1.3 (1.2-1.4), drug
      poisoning; OR 1.8 (1.7-2.0), non-drug poisoning; OR 1.4 (1.3-15) and scald
      injuries; OR 1.1 (1.1-1.5), while injuries with ingestion/intrusion of foreign
      objects tended to vary little with socio-economic indicators. CONCLUSION: Infants
      and toddlers in families with young mothers and in families on social welfare are
      at particular risk for home injuries in Sweden. The knowledge that the risk of
      poisoning, scalding and ingestion of foreign objects is related to specific ages
      can be used in timing of parent counselling.

PMID- 11227337
TI  - Growth hormone in short children: beyond medicine?
AB  - The indications for growth hormone (GH) treatment in non-GH-deficient short
      children are in debate, with some arguing that this treatment does not belong
      solely in the medical domain. We describe three different approaches to the
      issue, and argue that neither a disease-oriented nor client-oriented approach is
      sufficient. Both lead to withdrawal of medical interventions or to an undesirable
      application. CONCLUSION: An approach focusing on suffering as an indication for
      treatment of short stature is the most appropriate. The challenge is to develop
      proper tools by which to evaluate suffering and the efficacy of GH treatment in
      these children in order to relieve or prevent suffering.

PMID- 11227338
TI  - Establishment of intestinal microbial functions at birth: bilirubin and bacteria.
AB  - At birth, several "cross-talks" are rapidly established between the child and its
      developing microflora. Bile pigments and bile acids represent host-derived
      compounds that are acted upon by this microflora, thereby creating possibilities
      for several cross-talks of both physiological and pathophysiological importance.
      The major aim of this article was to characterize and quantitate individually the
      bilirubin pigments by newly developed methods. The results clearly demonstrate
      that quantitative and qualitative alterations in bilirubin metabolism occur
      shortly after birth. CONCLUSION: It is hoped that the methodological improvements
      will create new interest in bilirubin and its metabolism in early infancy.

PMID- 11227339
TI  - Intra-amniotic endotoxin accelerates lung maturation in fetal rabbits.
AB  - The hypothesis that endotoxin in amniotic fluid accelerates fetal lung maturation
      was tested. On day 25 of gestation, LPS (5 microg/fetus) was injected intra
      amniotically into one uterine horn of eight New Zealand white rabbits, whereas
      the contralateral amniotic sacs were injected with saline vehicle. The fetuses
      were delivered 48 h after LPS administration and their lungs were studied. One
      dam went into premature labor prior to the 48 h time point and was excluded from
      the study. Mean white cell counts in amniotic fluid and bronchoalveolar lavage
      fluid from LPS-treated fetuses were increased 3.2-fold (p = 0.04) and 9.9-fold (p
      = 0.04), respectively. Fetal weights and lung weights were not affected by LPS.
      Surfactant protein SP-A and SP-B mRNA expressions in LPS-treated fetuses were
      increased 2.3-fold (p = 0.03) and 1.4-fold (p = 0.04), respectively. Static lung
      compliance was increased in animals treated with LPS (p = 0.001). Lungs from LPS
      treated animals had better aeration than those of controls. Mean volume of
      inflation-fixed lungs of LPS-treated fetuses was 1.7 times greater than that of
      controls (p = 0.03). CONCLUSION: Intra-uterine exposure to LPS increases
      surfactant protein expression and improves lung stability and aeration in preterm
      animals.

PMID- 11227340
TI  - Bilirubin-IXalpha and -IXbeta pigments, coproporphyrins and bile acids in
      meconium and stools from full-term and preterm neonates during the first month of
      life.
AB  - Individual bilirubin pigments in the excreta were quantitated by newly developed
      methods. In meconium, bilirubin-IXbeta predominated, whereas bilirubin-IXgamma
      and -IXdelta remained undetectable. The daily excretion of bilirubin-IXalpha plus
      -IXbeta was 0.03-1.00 and 0.04-2.00 micromoles kg(-1) of birthweight in preterm
      and full-term infants, respectively. The ratio of bilirubin-IXalpha to -IXbeta in
      meconium was 0.25 +/- 0.34, 0.32 +/- 0.30 and 0.46 +/- 0.55 in newborns of
      gestational ages below 30, from 31 to 36 and above 36 wk, respectively. The
      predominance of bilirubin-IXbeta disappeared within the first week in those with
      gestational age >31 wk but more slowly in the very preterm group. The ratio of
      monoconjugated to diconjugated bilirubin-IXalpha was 4 to 5 in full-term infants,
      whereas this ratio was only reached after 1 mo in preterm infants. The ratio of
      glucuronide or glucoside to xyloside varied widely, independent of gestational
      age. No correlation between faecal UCB-IXalpha and beta-glucuronidase was
      observed. The daily coproporphyrin excretion fell from a median of 500 microg on
      day 1 to below 20 microg from day 7 onwards; this decrease correlated with that
      of bilirubin-IXbeta. The daily 3alpha-hydroxylated bile acid loss in the excreta
      was two- to fivefold higher than in the adult; this, together with the higher
      neonatal serum levels (12-90 nmoles ml(-1)), indicates an immature intestinal
      reabsorption and an enhanced bile acid synthesis. CONCLUSION: Both zinc
      coproporphyrin and bilirubin-lXbeta are characteristic compounds of human
      meconium, diconjugated bilirubin-IXalpha is low or absent in meconium of very
      preterm infants, and faecal and serum bile acids are high.

PMID- 11227342
TI  - Effect of gender in response to an aerobic training programme in prepubertal
      children.
AB  - The aim of the present study was to investigate the gender effect of an endurance
      training programme on the maximal oxygen uptake (VO2max) of prepubertal children.
      The subjects comprised eighty-five 10-11-y-old prepubertal children: 35 (17
      girls, 18 boys; EG) were involved in a 13-wk running training programme and 50
      (22 girls, 28 boys; CG) served as a control group. Each subject carried out a
      continuous and progressive cycle ergometer test before and after the 13-wk study
      period under the same conditions and procedures. Oxygen consumption, carbon
      dioxide, ventilation and heart rate (HR) were continuously monitored during the
      test. The training programme consisted of interval and continuous long-distance
      running (frequency: 3 times a week, duration: 1 h per session, intensity: higher
      than 80% of maximal HR). V02max significantly increased after the training
      programme for EG (before = 42.3 +/- 7.7, after = 45.3 +/- 7.5 ml x min(-1) x kg(
      1), p < 0.01), while no alterations were noticed for CG (before = 43.1 +/- 6.7,
      after = 42.6 +/- 7.6 ml x min(-1) x kg(-1), p < 0.01). Such an increase was
      higher in the girls (+9.1%) than the boys (+4.6%). The lower initial fitness of
      the girls could explain this, however, because a significant relationship was
      found between the percentage of VO2max increase after training and the initial
      VO2max. The present longitudinal study shows that maximal oxygen uptake can
      increase in prepubertal children after an aerobic training programme and that
      such an increase is of the same order in boys and girls when the initial aerobic
      fitness is taken into account.

PMID- 11227341
TI  - Aetiological factors in neonatal cholestasis.
AB  - The aim of the study was to investigate factors of possible importance for the
      aetiology of neonatal cholestasis. The medical records of 85 cholestatic infants
      were retrospectively reviewed. The most common diagnoses were extrahepatic
      biliary atresia (n = 30 patients), alpha1-antitrypsin deficiency (n = 11) and
      progressive familial intrahepatic cholestasis (n = 11). The mothers of the
      patients with biliary atresia had a higher mean age and were more commonly
      treated for gestational diabetes than the mothers of patients with intrahepatic
      neonatal cholestasis. The morbidity and mortality in the siblings of patients
      with biliary atresia were also greater than expected. There was a seasonal
      variation of the birth months in the biliary atresia group. possibly indicating
      an association to viral infections. Signs of ongoing cytomegalovirus infection
      were more common in both the extrahepatic and the intrahepatic group.
      CONCLUSIONS: Progressive familial intrahepatic cholestasis may be a more common
      cause of neonatal cholestasis in Sweden than reported elsewhere. A maternal
      vulnerability, of genetic or other origin, is suggested in the aetiology of
      biliary atresia. The true pathogenetic importance of cytomegalovirus infection in
      patients with neonatal cholestasis of different origins remains to be
      established.

PMID- 11227343
TI  - Importance of insulin content in infant diet: suggestion for a new infant
      formula.
AB  - Oral insulin promotes intestinal maturation and may prevent diabetes in animal
      models. The aim of this study was to evaluate the concentration of insulin in
      human milk and in different infant formulas. Our results show that the
      concentration of insulin in human milk is significantly higher (60.23 +/- 41.05
      microU/ml mean +/- SD) compared with cow's milk (16.32 +/- 5.98 microU/ml mean +/
      SD) and that insulin is hardly detectable in infant formulas. We propose the
      addition of human insulin to infant formula to match its composition more closely
      to human milk.

PMID- 11227344
TI  - Early sepsis, obstructive jaundice and right-sided diaphragmatic hernia in the
      newborn.
AB  - A male newborn was admitted to our Unit because of early sepsis and shock. He
      required antimicrobial therapy and mechanical ventilation and initially did well,
      although he exhibited jaundice and cholestasis. During the second week he
      deteriorated, with radiological opacification of the right hemithorax and pleural
      effusion, and did poorly in spite of antibiotical therapy and drainage of the
      effusion. In the third week, the X-ray suggested some bowel loops in the right
      hemithorax. A right-sided diaphragmatic hernia was confirmed by a CT-scan, and
      surgery was performed with good outcome. The association of delayed-onset right
      sided CDH following early sepsis and obstructive jaundice has not been published
      before, and illustrates a scarcely known form of presentation of this condition.

PMID- 11227345
TI  - Impaired IgG responses in a child with homozygous C2 deficiency and recurrent
      pneumococcal septicaemia.
AB  - Homozygous deficiency of the second component of complement (C2) is the most
      common inherited deficiency of complement. Although C2 deficiency has been
      detected in asymptomatic individuals, patients usually present with either
      autoimmune disease or recurrent pyogenic infection, particularly due to
      encapsulated bacteria such as Streptococcus pneumoniae, Haemophilus influenzae
      type b and Neisseria meningitidis. Interestingly, infection is the most common
      mode of presentation of C2 deficiency in young children (1). An association
      between C2 deficiency and IgG subclass deficiency has also been previously
      described. We now report a female child with C2 deficiency that presented at the
      age of 3 mo with recurrent pneumococcal septicaemia. Although IgG subclass levels
      were normal, specific IgG responses to vaccination against S. pneumoniae and H.
      influenzae were significantly impaired.

PMID- 11227346
TI  - [Osteochondral lesions of the talus--a rarity?].

PMID- 11227347
TI  - [Diagnostic imaging of acute and chronic osteochondral lesions of the talus].
AB  - Acute fractures involving the articular surface of the talus run parallel to the
      surface and are confined to the cartilage and/or the immediate subchondral
      cancellous bone. Subchondral microfractures ("bone bruises"), osteochondral
      fractures and solely chondral fractures are different manifestations of impaction
      injuries that affect the articular surface. This article reviews the radiologic
      appearance of acute osteochondral lesions of the talus and comments on the role
      of the noninvasive imaging modalities. Conventional radiography and MRI provide
      the most relevant information and are widely discussed. A MRI classification is
      presented emphasizing the distinction between lesions with intact and disrupted
      cartilage. Osteochondrosis dissecans (OCD) is a chronic osteochondral lesion. It
      is diagnosed in most cases by conventional radiography. MRI has become a decisive
      tool in staging the lesions. Intact cartilage and contrast enhancement of the
      lesions are findings of MRI stage I. Cartilage defects with or without incomplete
      separation of the fragment, fluid around an undetached fragment, cysts larger
      than 5 mm in diameter and a dislodged fragment are MRI findings observed in stage
      II and operative treatment has to be considered.

PMID- 11227348
TI  - [Etiology and pathogenesis of osteochondrosis dissecans tali].
AB  - Osteochondritis dissecans of the talus is a particular form of osteochondral
      lesions of the talus. A trauma with subsequent osteochondral defect detected
      immediately by radiology has to be differentiated from osteochondritis dissecans
      of the talus. Osteochondritis dissecans (o.d.) is primarily a disease of the
      subchondral bone and can affect almost every joint in the human organism. After
      the knee and elbow, the talus is the third most common site of the disease
      accounting for 4% of all cases. It mostly arises in the 2nd decade but can occur
      at almost any age. Different etiological factors of osteochondritis dissecans
      (vascular, traumatic, infectious, endogenous, genetic) are discussed in general
      and in particular for the talus. In the literature, the etiopathogenetic
      mechanism of trauma is favored. Several studies show an anamnestic coincidence of
      distortsion and/or supination trauma prior to the onset of o.d. at the talus. The
      most common localization of the o.d. lesion is the middle and posterior third of
      the medial and less frequently anterior and middle third of the lateral talus.
      Biomechanical experiments demonstrated that these areas are those with the
      highest load under varus/valgus and pronation/supination stress. Trauma is held
      responsible for both the more frequent medial, cup-shaped lesion and the less
      frequent lateral, wafer-shaped lesion. Taking into consideration the complex
      motion patterns of the ankle joint, these conceptions should be abandoned and the
      exact pathomorphogenetic mechanism assessed more closely in future. Other
      possible etiological factors such as genetic, metabolic or infectious causes are
      discussed but are not yet substantiated by scientific and experimental evidence.
      The different stages of o.d. do not differ from the stages in other joints and
      from aseptic osteonecrosis. Theoretically, it seems that o.d. is initiated when
      an imaginary threshold value is reached so that a subchondral osteonecrosis
      occurs (stage I). Repetitive mechanical forces possibly interfere with the
      regeneration process of the lesions, resulting in the development of a
      subchondral sclerosis (stage II). Further disturbance of the regenerative process
      may lead to a demarcation of the osteochondral area (stage III) and eventually
      dissecation (stage IV) of the fragment with loose bodies in the joint. Clinical
      symptoms are nonspecific. Periarticular swelling, hydrarthrosis, reduced range of
      motion and sometimes joint locking are the most common clinical signs.
      Differentiation of o.d. from posttraumatic osteochondral lesions of the talus is
      sometimes difficult or even impossible. In contrast, other entities of the
      tibiotalar joint (such as talar necrosis or subchondral ganglion) can be easily
      distinguished.

PMID- 11227349
TI  - [Treatment strategies in osteochondral lesions of the talus. Review of the
      literature].
AB  - The aim of this study was to compare the results of different treatment
      strategies for osteochondral defects (OCD) of the talus. Electronic databases
      from 1966 to June 2000 were systematically screened. Thirty-nine studies
      fulfilled our inclusion criteria. No randomized clinical trials could be
      identified. The results of nonoperative treatment were described in 14 studies,
      of excision alone in 4, of excision and curettage in 10, of excision, curettage
      and drilling in 21, of cancellous bone grafting in 2, of fixation in 3, and of
      osteochondral transplantation in 1. Good or excellent results were found in 45%
      of the cases. Comparison of different surgical procedures showed that excision,
      curettage and drilling resulted in the highest mean success rate (86%), followed
      by excision and curettage (76%) and excision alone (38%). From the results of
      this systematic review we conclude that nonoperative treatment and excision alone
      are not to be recommended for treatment of talar OCD. Excision, curettage and
      drilling produced a high percentage of good or excellent results. Further
      randomized, controlled trials are required to compare the outcome of these two
      surgical strategies for OCD of the talus.

PMID- 11227350
TI  - [Anatomy and biomechanics of the upper ankle joint].
AB  - The ankle joint as a component within the construction of the foot must be seen
      as a compromise between the static and dynamic demands made upon it. In this
      article the structure and function of the ankle joint are described with special
      reference to the formation of morphological parameters such as the distribution
      of subchondral mineralization, cartilage thickness, subarticular cancellous bone
      and mechanical properties. These parameters could be seen as a biological
      reflection of the individual mechanical conditions.

PMID- 11227351
TI  - [Arthroscopic treatment of osteochondral lesions of the talar dome].
AB  - Osteochondral lesions of the talus (OLT) may be either traumatic or caused by an
      osteonecrosis of unknown origin. The different types of OLT differ in their
      radiological aspects, their treatment and their prognosis. Whereas traumatic OLTs
      are generally located on the lateral talar dome, chronic necrotic lesions are
      preferentially located on the medial talar dome. The former have a better
      prognosis. Arthroscopy is in many cases the treatment of choice. This study
      presents several arthroscopic treatment options for osteochondral lesions of the
      talus. Traumatic fragment excision, osteosynthesis of larger fragments on the
      anterolateral talar dome, and excision and curettage of necrotic lesions may
      provide good results. In the absence of chondral damage in chronic osteonecrotic
      lesions, we prefer a transmalleolar drilling. Arthroscopic treatments are
      relatively simple procedures for trained arthroscopists with a low complication
      rate. With larger OLTs, open procedures using osteochondral autografts or
      cancellous bone grafts are preferred to arthroscopy.

PMID- 11227352
TI  - [Approach to open treatment of osteochondral lesions of the talus].
AB  - Arthroscopic techniques still represent the treatment of choice in osteochondral
      lesions of the talus (OLT). Open techniques may be used as an alternative or may
      be complementary to arthroscopic treatments. They are especially indicated in
      cases of large osteochondral lesions, difficult localisations and in cases of
      recurrent interventions. In addition to the type of treatment for the lesion
      itself, the choice of an ideal surgical approach is of paramount importance.
      Indications, operative technique, possible complications and rehabilitation are
      described in detail for each approach. Anterolateral, anteromedial,
      posterolateral and posteromedial soft-tissue approaches as well as medial and
      lateral malleolar osteotomies are discussed. If a distraction is not desired with
      arthroscopy, posteromedial and posterolateral soft-tissue approaches offer a good
      alternative for the treatment of posterior OLT. Osteotomy of the (medial)
      malleolus offers good visualisation of the medial talar dome. With the
      introduction of new techniques of osteochondral transplantations, the use of this
      approach is becoming more popular. However, it is an invasive technique and the
      risk of secondary osteoarthritis after malleolar osteotomy still needs to be
      determined.

PMID- 11227353
TI  - [Operative therapy of osteochondral lesions of the talus with autologous
      cartilage-bone transplantation].
AB  - Since 1996 we have gained experience in the development and clinical application
      of the OATS technique in 167 cases. Operative management, technical demands and
      early results of osteochondral cylindrical autograft plugs at the talus are
      presented. Between April 1996 and November 2000 we treated 39 patients (21 male,
      18 female) with an average age of 28.4 years (range: 16-57 years) for
      osteochondral defects with an average size of 8 x 15 mm-20 x 15 mm at the medial
      (n = 31) and lateral (n = 6) talar dome as well as at the distal tibia (n = 2)
      with an OATS technique. Indications were osteochondral defects after trauma in 12
      patients (med., n = 5; lat., n = 5; dist. tibia n = 2) and osteochondrosis
      dissecans (grades III and IV) in 27 patients (med., n = 26; lat., n = 1). The
      donor site was the proximal lateral femoral condyle in all patients. An
      additional osteotomy of the malleolus was necessary in 30 patients. All patients
      were scored pre- and postoperatively by a Lysholm Bruns score and monitored by
      postoperative MRI. The follow-up extended for an average of 19.6 months (6-42).
      The Lysholm score for all patients rose from 62 points (range: 20-77) up to 92
      points (range: 63-100). There was no correlation between patients with and
      without an osteotomy of the malleolus. The postoperative MRI showed a complete
      incorporation and vitality of the transplanted cylinders as well as a congruence
      of the joint surface. Complications were pain in three cases in the region of the
      osteotomy, which decreased after removal of the screws, and synovialitis in one
      case. One patient reported femoropatellar pain for about 4 weeks. The OATS
      technique achieves encouraging results in limited osteochondral defects in the
      talar dome even in preoperated osteochondral defects. Because of the mostly
      posterior localization of the defect zone, osteotomy of the malleolus is
      necessary in most cases. Harvesting the donor cylinders from the ipsilateral knee
      joint by mini-arthrotomy shows a low mortality. The OATS technique is a suitable,
      causal and cost-effective therapy, which can possibly prevent and at least delay
      the development of an arthrosis.

PMID- 11227354
TI  - [Computer-assisted retrograde drilling of osteochondral lesions of the talus].
AB  - Treatment principles of osteochondral lesions of the talus usually consist of
      debridement of the chondral part and methods that attempt to stimulate
      revascularization of the necrotic bony part of the lesion. The latter is mostly
      achieved through multiple drilling of the subchondral zone. Dorsomedial talar
      dome lesions are frequently inaccessible with antegrade drilling techniques. In
      addition, if the cartilage surface over the bony lesion is still intact, it can
      be injured by antegrade drilling. To overcome these potential problems,
      retrograde drilling techniques have been developed using drill guides or
      intraoperative fluoroscopy. Our proposed method of computer-assisted retrograde
      drilling is an advancement of these techniques. The use of 3D navigation provides
      the possibility for placing a guide wire exactly in the center of the lesion
      defined on preoperative MRI or CT scans. This guide wire can then be overreamed
      with cannulated reamers followed by retrograde bone grafting of the lesion or
      allows multiple retrograde drilling of the subchondral plate using a parallel
      drill guide. We found that computer-assisted retrograde drilling could improve
      precision, avoid misplacement of guide wires, and reduce the time of surgery and
      intraoperative fluoroscopy.

PMID- 11227355
TI  - [Traumatic osteochondral lesions of the talar dome].
AB  - Trauma is currently accepted to be the main etiologic factor causing OCL of the
      talus. Displaced lesions are easily recognized clinically and radiographically
      and treated surgically. In other cases, radiographic findings are often
      remarkably discrete or even absent. If symptoms persist, surgical treatment is
      warranted. In our series of 27 patients with traumatic talar OCL, operative
      treatment achieved good/excellent results in 88% of primary cases and
      good/excellent results in 80% of recurrent cases. The interval between trauma and
      surgery averaged 20 months (6-60). No radiographic signs of arthritic changes
      were observed at 2-11 years follow-up. All lesions were treated by arthroscopic
      excision, curettage and drilling, and this is currently the treatment of choice.

PMID- 11227356
TI  - [Hemialloarthroplasty of the knee joint. Results of 2 different gliding
      prosthesis models].
AB  - The outcome of 2 different unicompartimental knee arthroplasty procedures (St.
      Georg, Link AG, and Wessinghage, Sulzer Medica AG) is presented. The clinical
      results were evaluated by use of the Insall Score (Knee Society Rating System).
      According to this system, the subjective opinion of the patients are presented as
      a "Function Score" and the clinical evaluations is shown as a "Knee Score". In
      this study, the median follow-up for the St. Georg implant was 7 years and 6
      months with good results reported by both scores. The median follow-up for the
      Wessinghage implant was 3 years and 2 months and it also showed good results.
      Despite the high average age of the patients in this study as well as the high
      percentage of female patients, both types of prostheses produced good results. If
      any, partial or complete radioluciencies were mainly observed in the tibial
      component. However, they had no clinical consequence. It should be noted,
      however, that arthritis in the compartment not receiving arthroplasty surgery
      progressed in almost 2/3 of the patients. By implantation of both implants a
      physiological axis of the leg could be achieved. The survivorship of the St.
      Georg implant was 88.92% (10 years survivorship). For the Wessinghage implant it
      was 98.35% (5 years survivorship).

PMID- 11227357
TI  - [Acute renal failure. Epidemiologic observations in the Piedmont region].
AB  - BACKGROUND: The use of ICD9-CM for the classification of disease has been
      introduced in Italy. A retrospective study has been performed to evaluate the
      incidence of Acute Renal Failure Dialysis treated (ARFD) in Piedmont (4,500,000
      inhabitants) and to evaluate the use of ICD9-CM for the classification of Acute
      Renal Failure (ARF) in the compilation of Hospital Discharge Sheets (SDOs).
      METHODS: The Piedmont Renal Transplant Registry was used to look for episodes of
      ARFD in the Region in 1997. All cases of ARF (584,5,6,7,8,9- 997.5- 958.5- 788.9-
      634.3-639,3-669.3) were looked for in SDOs of all admissions to hospitals in the
      Region in the same period. RESULTS: 646 episodes of ARFD were found in the
      Piedmont Registry, that is an incidence of 142 episodes/million/year. 830
      episodes of ARF (184 episodes/million/year) were found in an analysis of SDOs. It
      is impossible to find cases of ARFD from an analysis of SDO data. CONCLUSIONS:
      The ICD9-CM system, in Piedmont, in 1997, wasn't well utilized and the data are
      not useful for epidemiological studies unless further education in their use has
      been carried out. The analysis of the Piedmont Registry evidences that in the
      Region all the cases of advanced ARF (creatinine > 5 mg%) are treated by
      Dialysis. This may indicate a good performance of nephrological care, but the
      data have to be confirmed, because the incidence of ARFD is higher than in other
      European countries.

PMID- 11227358
TI  - [Relationship between risk profiles, prognosis, and outcome of patients with
      acute renal failure treated with dialysis].
AB  - BACKGROUND: The paradox of the increased mortality in the patients with acute
      renal failure (ARF) although submitted to better cares and newer renal
      replacement therapies (RRT) has recently prompted to the use of quantitative
      individual severity scores (ISS) calculating for each patient an individual death
      probability (DP) in correlation with the risk covariates found before the start
      of RRT; beside the clinical use, the ISS allow an evaluation of the effect of
      strategies and modalities of treatments as quantitative additive factors
      eventually added or subtracted to the base-line individual background of risk.
      The ideal index should be chosen on the basis of its precocity (origin just at
      the start of therapy), sensitivity (true positive against false positive
      results), universality (independence from the development set) and discriminative
      power (the capability to discern patients potentially treatable from those with
      an unchangeable prognosis). Indexes already validated in their development set
      should be used and studied into a different set ("evaluation set"). METHODS: The
      aim of this study has been: to evaluate a literature index (ATN-ISS, Liano,
      developed prospectively in a remote set) in the local (A) environment on 340
      patients with ARF successively treated with dialysis (mostly hemo-filtration)
      studied retrospectively along a 4 year period in our regional hospital and
      compare its performances with a local index (PDTOR) developed by logistic
      analysis in the same pool; the fitness of both tests to the real outcome has been
      evaluated by the Limeshow test and by ROC curves; to compare both indexes in a
      remote environment (B) of a dialytic pool of 345 patients extracted by a group of
      25721 patients treated by 25 Italian ICU (Archidia Study group). The responses of
      the two indexes have been compared even with the index (SAPSII) prospectively
      generated at the admittance in the ICU by the Archidia Group. RESULTS: In the
      local set (A) TOR-ISS fits well with the outcomes (Limeshow test C2 = N.S.) as
      expected being evaluated in its own "development" set, while ATN-ISS
      significantly underestimates deaths, perhaps working on a retrospectively built
      data-base, that could contain fewer risk elements than necessary. (B) In the
      remote set, ATN-ISS fits very well, while TOR-ISS significantly overestimates
      expected deaths, for its retrospective origin or for a real lower death incidence
      compared to that of its development set. SAPSII shows no correlation at all with
      the outcome because its calculation is often well before (10 days on average)
      than the actual start of dialytic treatment. CONCLUSIONS: In conclusion ATN-ISS,
      an index built prospectively on a large cohort of patients, fits correctly in a
      remote prospectively built evaluation set. Retrospective built indexes or data
      base don't allow a correct ISS evaluation while ICU indexes (SAPSII, APACHE),
      generated at the admittance in the ICU should not be used for ARF patients
      submitted to dialysis.

PMID- 11227359
TI  - [Treatment of fluid overload and kidney failure with periotoneal dialysis after
      heart surgery].
AB  - BACKGROUND: Infants undergoing cardiac surgery with prolonged cardio-pulmonary
      bypass are particularly exposed to the risk of acute renal failure for renal
      hypoxia due to low cardiac output. METHODS: To limit fluid overload deriving from
      oligo-anuria and low cardiac output we have recently adopted an early peritoneal
      dialysis protocol, positioning the peritoneal catheter during the intervention
      and performing early exchanges at first signs of inadequate diuretic response
      and/or "leaky capillary syndrome" with diffuse edema. From 1-1 to 31-12-1997 12
      patients (8 males), of median age of 65.5 days (range 1-350 days) and median
      weight of 3463 g (range 2380-6550 g) were treated with peritoneal dialysis
      (automated exchanges of 10 ml/kg body weight of 1.5% glucose, dwell time 20
      minutes). Cardiac pathologies included complex hearth malformations.
      Cardiopulmonary bypass lasted a mean of 202 minutes (range 102-372 minutes). The
      children were treated for a minimum of 1 to 42 peritoneal dialysis sessions. The
      infusional therapy included human albumin and fresh frozen plasma to substitute
      losses and furosemide at the dose of 4 mg/kg/day to reduce the "leaky capillary
      syndrome". RESULTS: The results were very satisfactory: only 3 children died in
      the first 30 days after surgery. Renal function was normal at the end of the
      observation in 8/12 cases, and 2 cases presented chronic renal failure.
      CONCLUSIONS: Since similar series report a mortality rate of 33-79%, it is
      suggested that early peritoneal dialysis may have positively influenced the final
      survival rate.

PMID- 11227360
TI  - [Acute kidney failure caused by cholesterol atheroembolism].
AB  - BACKGROUND: To describe the clinical aspects of renal failure due to cholesterol
      atheroembolism. METHODS: An hospital based observational study on renal failure
      due to cholesterol atheroembolism was carried out. Twenty-two cases (19 males,
      mean age 68 yrs, range 53-83 yrs) were identified from January 1992 to September
      1998. RESULTS: Clinical symptoms were acute or rapidly progressive renal failure
      with blue toe and/or skin livedo reticularis in 13/22 cases (59%) and indolent
      progressive renal failure in 7/22 cases (32%). In 6/22 cases (27%) an abdominal
      organ involvement was evident; two (9%) had retinal cholesterol emboli, two (9%)
      peripheral and two (9%) central nervous system impairment. In 7 patients (32%)
      the cholesterol atheroembolism occurred spontaneously, while in 15 (68%) it
      followed invasive or interventional radiology (8 cases, 36%); cardiac or vascular
      surgery (4 cases, 18%); thrombolytic or anticoagulant therapy (3 cases, 14%). The
      time interval between the procedure at risk and the onset of symptoms or signs of
      cholesterol atheroembolism ranged between few hours to 60 days. Eleven patients
      (50%) required dialysis, which was then withheld in 4 cases (36%), owing to
      partial functional recovery after a median time of 30 days, ranging from 10 to
      690 days. Median follow-up was 2.5 months (ranging from 2 days to 68 months), and
      eleven patients (50%) deceased. CONCLUSIONS: Cholesterol atheroembolism is a
      cause of renal failure associated with high mortality rates; its prevention needs
      the skill of all physicians involved in the care of patients with severe
      atherosclerosis.

PMID- 11227361
TI  - [Acute kidney failure and losartan: a recently observed event of antagonists of
      angiotensin II AT1 receptors].
AB  - Losartan is the first of a new category of drug that inhibits angiotensin II (ANG
      II) AT1 receptors antagonists. This drug lowers blood pressure by inhibiting the
      activity of ANG II and reduces proteinuria and progression of chronic renal
      failure (CRF). It seems therefore an extremely interesting drug. Aim of this
      study is to describe 3 cases of acute renal failure (ARF), occurred during
      therapy with losartan. None of the patients showed renal arteries stenosis or
      other predisposing factors for the development of ARF. In conclusion, we want
      pointed out that losartan could affect renal function in a similar way as
      angiotensin converting enzyme inhibitors (ACEI). We suggested that use of
      losartan in risk situations, like old age, preexiting CRF, stenosis of renal
      arteries, solitary kidney and diuretic therapy, should be carefully monitored as
      well as that of ACE I.

PMID- 11227362
TI  - [Morbidity and mortality in patients undergoing dialysis. Comparison of
      hemodialysis and peritoneal dialysis. Our experience].
AB  - BACKGROUND: We have compared the hemodialysis and peritoneal dialysis populations
      of our Center for morbidity and mortality, in a retrospective study of six years
      of activity. METHODS: We enrolled 125 patients (104 patients/year/million
      inhabitants), who had been in chronic dialysis from 1992 to 1997: 90 (22-90 years
      old) initiated in hemodialysis and 35 (27-82 years old) in peritoneal dialysis.
      RESULTS: We have evaluated survival and morbility, as
      hospitalization/patient/year in both groups. Mortality did not prove
      significantly different in the two groups. The global average of hospitalization
      was 8 days/patient/year for hemodialysis and 6 for peritoneal dialysis.
      CONCLUSIONS: In spite of the short time of observation and the exiguity of
      numbers, our experience shows that the two methods are equivalent.

PMID- 11227363
TI  - [Research potential of a regional registry].
AB  - BACKGROUND: The need for data bank gathering information in dialysis patients is
      as old as dialysis. Dialysis Registries presently active are characterized by
      different policies of data gathering (large vs small number of information) and
      of use (research vs economical or clinical purposes). Aim of the work was a
      discussion on the use of a Regional Registry (RPDT, Regional Registry of Dialysis
      and Transplantation of Piedmont, Italy), gathering since 1981 a wide set of
      information (about 80 items) on all patients treated in a relatively small area
      (about 4,300,000 inhabitants). METHODS: Two researches were selected: the first
      includes patients treated for > or = 20 years by RRT. Cases were identified on
      the basis of RPDT data and an inquiry regarding all patients was performed, with
      specific interest on comorbidity. The second includes diabetic patients on
      regular RRT, a sample of which was further analyzed in high detail. RESULTS AND
      CONCLUSIONS: While a Regional Registry, even gathering a wide set of data is
      unable to answer to the most qualitative questions, such as quality of life, its
      archives are a powerful tool to identify cases. Furthermore, ad hoc inquiries may
      represent a way to control quality of data or to test new fields to be studied.
      In the case of patients with long RRT follow-up, comorbidity questions were
      tested before being included on RPDT. In the case of a sample of diabetic
      patients, type of diabetes and cause of ESRD were controlled. This biunivocal
      relationship between clinical work-up and epidemiological archives may often
      interest future perspectives.

PMID- 11227364
TI  - [Epidemiologic analysis of the incidence of new diabetic patients on dialysis as
      a basis for a clinical study].
AB  - BACKGROUND: Aim of this study is to analyse the incidence of diabetic patients
      starting dialysis in Piedmont (Italy) during the period 1981-1996 and to
      evaluate, in a subgroup of patients, the causes of uremia (diabetic nephropathy
      or other), and the type and seriousness of comorbid factors, in order to define
      the clinical conditions and try to explain the causes incidence increase.
      METHODS: Data are taken from the RPDT (Regional Registry of Dialysis and
      Transplantation of Piedmont). RESULTS: Total incidence of new patients starting
      dialysis in this Region increased from 65 pmp in 1981-1982 to 116 pmp in 1995
      1996 and the mean age increased from 55.4 +/- 15.5 years in 1981-1982 to 61.5 +/-
      15.6 in 1995-1996; 49% of patients had at least one of the 13 conditions of
      comorbidity considered by the Registry (including severe vascular, cardiac,
      systemic diseases and diabetes). In the same period the incidence of diabetic
      patients increased from 6 pmp (1981-1982) to 19 for males and 12 pmp for females
      (1995-1996); this increase is higher for males and limited to patients with age >
      or = 60 years (for example: group 70-79 years from 7 to 56 pmp). A study
      performed in a group of 64 patients (52 type 2 and 12 type 1) showed the
      incidence of multiple comorbid factors: the most important in type 2 are vascular
      diseases (44/52) and heart diseases (20/52); blindness and amputations are
      relatively rare (2 each). An important comorbid factor in type 1 diabetes is
      blindness (3/12) and in this group the most frequent cause of uremia is diabetic
      nephropathy (DN) (9/12); in the group of type 2 patients nephroangiosclerosis and
      a clinical picture of progressive renal failure, without nephrotic syndrome,
      represents 48% of all diagnoses. CONCLUSIONS: These results underline the
      necessity of a strict collaboration with diabetologists and of an improvement of
      dedicated structures in order to meet the increase of this critical population.

PMID- 11227365
TI  - [Assessment of reticulocyte hemoglobin content as a guide for iron
      supplementation in hemodialyzed patients].
AB  - BACKGROUND: In literature the reliability of reticulocyte hemoglobin content
      (CHr) has been recently emphasized to detect "functional" iron deficiency induced
      by erythropoietin therapy. METHODS: In the present work the behavior of CHr in 68
      uremic patients hemodialysis has been evaluated. RESULTS: Its values appeared
      poorly correlated (R2 = 0.32) to the hypochromic erythrocyte percent values, and
      furthermore CHr sensitivity seemed poor, with pathologic low values detected in
      three cases only, all characterized by reduced mean corpuscular volume (MCV).
      CONCLUSIONS: In the cases personally observed, MCV and CHr are weakly correlated
      (R2 = 0.15); reticulocyte hemoglobin absolute value in personal opinion does not
      appear as a reliable index of iron deficiency, being rather dependent on
      reticulocyte volume.

PMID- 11227367
TI  - [Permanent central venous catheters for dialysis. The situation in Piedmont-Aosta
      Valley].
AB  - BACKGROUND: Permanent central venous catheters for hemodialysis have become
      increasingly important as vascular accesses for extracorporeal dialysis. The aim
      of this study was to evaluate the prevalence and various aspects of these
      catheters in the chronic dialysis population in Piedmont and Aosta Valley on 30-6
      1998 using a multiple-choice questionnaire. METHODS: A total of 2389 patients
      were receiving chronic hemodialysis. Permanent central venous catheters were
      present in 6.2% of the population (149 patients), arteriovenous fistulas in
      83.1%, vascular prostheses in 9.3% and temporary catheters in 1.4%. The site
      chosen for permanent catheters was the internal jugular vein in 88.6% of cases,
      the subclavian vein in 8.7% of cases and the femoral vein in 2.7% of cases. The
      double catheter is the most frequently used. In 76% of centres catheters are
      positioned by nephrologists. Thrombosis prophylaxis is performed in 98% of cases
      with heparin and the most frequently used disinfectant to dress the cutaneous
      exit is iodopovidone. RESULTS: This study highlights the important role played by
      permanent catheters. The double catheter was used in 64.4% of the entire
      population, confirming the greater efficiency of these catheters as reported in
      the literature. Operating autonomy is relative in 76.2% of centres where
      catheters are positioned by nephrologists who often use the collaboration of
      other specialists. CONCLUSIONS: The authors stress the need to reflect on the use
      of iodopovidone is to dress the cutaneous exit of catheters since this
      disinfectant is contraindicated by one of the largest manufacturers of silicone
      catheters owing to its harmful medium long-term effects.

PMID- 11227366
TI  - [Pharmacoeconomics in hemodialysis. Role of iron in the treatment with
      erythropoietin].
AB  - BACKGROUND: Although its efficacy is well known, the high economic cost of
      erythropoietin (EPO) raises the question of pharmacoeconomics in HD. An optimal
      Hb level with the lowest dosage of EPO seams to be correlated to the way of
      administration and an adequate iron supplementation. METHODS: The study evaluates
      the influence of iron supplementation on the control of EPO-related expenses.
      RESULTS: A serum ferritin level higher than 50 pg/ml in hemodialysis patients on
      chronic EPO therapy turned out to be adequate to keep an optimal Hb level. Our
      data show that this value, as far as pharmacoeconomic is concerned, is highly
      underestimated. CONCLUSIONS: A higher i.v. iron supplementation correlates with a
      significant raise of serum ferritin level and saves on EPO-related expenses up to
      1 million/per patient/per year.

PMID- 11227368
TI  - [Safety in dialysis rooms. Biologic risks].
AB  - The search for quality in the health service cannot lead aside the safety of its
      operators and users, subject to the well defined parameters of Law 626. This
      study makes a preliminary examination of the accidents occurring in our Health
      District which comprises three hospitals, 600 beds and 1,800 employees. A total
      of 172 accidents have been reported. The percentages can be broken down between
      the various sectors: 73% of accidents involve nurses, 9% involve doctors and 1%
      administrative personnel. The greatest risk in hemodialysis is the biological
      factor (through accidental cuts or pricks which account for 67% of the accidents
      reported) and involves humans (both patients and personnel), monitors and
      environments as the sources of pathogens. The most frequently isolated germs are
      E. coli and Pseudomonas. It has been shown that prevention is above all based on
      the accuracy with which procedures are followed. The risk of hepatitis C has not
      yet been resolved, as is affinned in a review reported in the study. The HIV risk
      gives the greatest cause for concern, even if only 0.2% after exposure compared
      to 15-36 for HbsAg. Compliance with universal rules for prevention and post
      exposure procedures provides an adequate guarantee for prevention.

PMID- 11227369
TI  - [Plasma levels of homocysteine in patients on hemodiafiltration].
AB  - BACKGROUND: Hyperhomocysteinemia is an independent risk factor for cardiovascular
      diseases, and is a common finding in patients on regular dialysis treatment.
      Hemodialysis lowers homocysteine plasma levels in variable amounts, and it was
      also suggested that folic acid and vitamin B12 supplements can reduce such
      levels. The purpose of the present study was to evaluate homocysteine plasma
      levels in patients on hemodiafiltration who received vit. B12 and folate
      supplements such as to keep their plasma levels in the normal range. METHODS: A
      retrospective study was carried out in a group of 36 patients on
      hemodiafiltration, who received routinely folate and vit. B12 supplements i.v.
      Pre-dialysis plasma levels of folate and vit. B12 and pre-postdialysis
      homocysteine concentration were evaluated. The latter was correlated with other
      parameters. RESULTS: The present study confirmed high homocysteine levels in
      patients on RDT and their reduction due to dialysis, demonstrated a weak negative
      correlation of pre-dialysis homocysteine with vit. B12 plasma level, but no
      correlation with folic acid. CONCLUSIONS: This study showed a good efficiency of
      hemodiafiltration using high permeability membranes on homocysteine removal,
      whereas the negative correlation between folate and homocysteine plasma level was
      not confirmed.

PMID- 11227370
TI  - [Conservative treatment of renal ptosis].
AB  - BACKGROUND: Nephroptosis or floating kidney is an acquired, caudal displacement
      of one or both kidneys, with differing stages and etiology. It has been almost
      completely ignored over the past few years. The general tendency to regard
      nephroptosis as a urological pathology has prompted researchers to look for
      resolutive surgical treatment. The existence of over 150 surgical techniques is a
      clear demonstration of the high failure rate with the result that surgeons are
      unwilling to tackle this pathology, often leaving the patient alone with his
      problems. The numerous nephrological complications caused by nephroptosis have
      prompted us to look for alternative therapies to propose to nephrologists for the
      consecutive treatment of the floating kidney, enabling the patient to live with
      his pathology. METHODS: A longitudinal study was performed for 60 months in 102
      patients with mono or bilateral nephroptosis. Hematuria, urinary cylindroids,
      asthenia, pain and the daily intake of antispastic lenitives were analysed at 6,
      12, 24 and 60 months. Throughout this period all patients were treated with a
      water cure (31/day) and nocturnal decubitus in Trendelenburg's position (the foot
      of the bed is raised by 10 cm). Patients with primary or secondary kidney
      pathology, UTI and nephrolithiasis were excluded from the study. RESULTS: All the
      parameters showed a marked and steady improvement. At one year, over half the
      patients treated had improved, and at two years over two thirds only complained
      of marginal symptoms. CONCLUSIONS: Quali-quantitative and temporal values are
      reported in the light of which we can affirm that conservative treatment enables
      the patient to lead an almost normal life, as well as returning to work, with a
      reduced risk of complications.

PMID- 11227371
TI  - [Etiopathogenic and therapeutic features in acute kidney insufficiency].

PMID- 11227372
TI  - [Fimbriae as a pathologic factor of bacteria and a carrier in conjugate
      vaccines].
AB  - Fimbriae play important role as pathogenic factors in many bacteria by their
      adhesive properties. Adhesin is located at the tip of fimbriae but also in other
      parts of fimbriae. Recent findings on structure of fimbriae genes and their
      expression for the biosynthesis and formulation of complete fimbriae have been
      described. Special attention was focused on the participation of fimbriae in the
      mechanism of pathogenesis and their specificity towards tissue receptors. Most
      recent studies have been performed on E. coli and Klebsiella and those data
      predominate in this work. Fimbriae can be used for the construction of vaccine as
      a proteinous carrier for haptenic carbohydrate epitopes. In conjugates fimbriae
      express distinct immunogenic, adjuvant and protective properties.

PMID- 11227373
TI  - [Partial dependence of luliberin and its analogs on the immune system].
AB  - Luliberin--luteinizing hormone-releasing hormone (LHRH) is the first link in
      hypothalamus-pituitary-gonads axis which participates in reproduction. This
      hormone and lutropin are released from immunological cells, however antagonists
      of LHRH inhibit this action. Some cytokines (IL-1 beta, GM-CSF) inhibit release
      of LHRH and others (IL-6, IFN-gamma) stimulate this release.

PMID- 11227374
TI  - [Quality control for HLA typing].
AB  - In November 1999 we started the quality control exercise for Polish institutions
      involved in HLA typing. Five out of eleven invited institutions responded
      favourably and took part in the first run of the workshop. In the second trial,
      presently reported, number of labs increased to eight. Each centre received 4
      blood samples for serological typing of HLA class I and 5 samples for DNA HLA
      class II typing. As in the previous workshop, HLA class II typing should be
      performed at least for DRB1 alleles at the low resolution level. The paper
      presents the results of the second run of standardisation.

PMID- 11227375
TI  - [TT virus--incidence and role in pathogenesis of liver diseases].
AB  - Recently discovered TT-virus is at present an object of intensive investigation.
      This paper reviews so far obtained controversial results dealing mainly with
      frequency of TTV occurrence and its potential significance in the development of
      liver disorders. On the basis of obtained results reported by many authors there
      is still lack of hard evidence showing significant role of TTV in the
      pathogenesis in liver diseases.

PMID- 11227376
TI  - [The role of PKC isoforms in tumorigenicity and apoptotic cell death].
AB  - Protein kinase C comprises a family of at least 13 distinct serine/threonine
      kinase isoenzymes that have important actions in transmembrane signal
      transduction pathways and have been reported to regulate cell proliferation,
      differentiation, cell-to-cell interaction, cytoskeletal functions, gene
      transcription, apoptosis and drug resistance. The results of investigations show
      differential redistribution isoenzymes in each organ and their specific activity
      in determined diseases.

PMID- 11227377
TI  - [Mechanisms for tissue transport of fatty acids].
AB  - Fatty acids (FA) play an important role in energy metabolism. They are not only
      used as substrates for energy production but are also involved in many other
      metabolic pathways. However, the exact mechanisms by which FA are taken up by the
      cells are not yet fully understood. Fatty acids circulating in blood cross the
      cell membranes partly via a mechanism facilitated by plasma membrane proteins and
      partly via a passive diffusion mechanism, the former mechanism being of major
      importance.

PMID- 11227378
TI  - [The significance of galanin in physiologic and pathologic processes in humans].
AB  - Galanin (GAL) a 29 amino-acid peptide, is distributed in the central and
      peripheral nervous system, the pituitary gland, the gastrointestinal tract and
      also in the endocrine and exocrine pancreas. The endogenous and exogenous effects
      of galanin are mediated by three receptor subtypes, which are termed: GALR1,
      GALR2, GALR3. Galanin has a significant role in physiological and pathological
      processes (acromegally, diarhoea, collitis, Alzheimer's disease, oberitas
      depression, pituitary gland adenomas) in a human body and animals. It has an
      ability to contract smooth muscles in gastrointestinal tract, stimulates reflexes
      in the central nervous system, decreases pancreatic amylase release, changes
      transport of electrolytes Na+ and Cl-, exerts tonic inhibition of nociceptive
      input to the central nervous system, stimulates glucagon release, inhibits
      insulin and somatostatin release, takes part in prolactin secretion, stimulates
      growth hormone--releasing hormone, hypothalamic gonadotropin releasing hormone
      and corticotropin releasing hormone. It causes increase of somatotropin
      secretion, foliculotropin and luteinizing hormone release and adrenocorticotropin
      secretion.

PMID- 11227379
TI  - [The significance of endothelin-1 in regulation of the circulatory system in
      hemorrhage shock].
AB  - Endothelin-1 (ET1), a 21-amino acid polypeptide, produced mainly in endothelial
      cells is the most potent mammalian vasoconstrictor peptide known. Haemorrhagic
      hypotension is accompanied by the increase in plasma ET1 concentration. The
      significance of this effect, however, is not clear. This paper reviews the causes
      of the rise in ET1 plasma concentration and the role of ET1 in cardiovascular
      regulation in haemorrhagic shock.

PMID- 11227380
TI  - [Clinical and genetic heterogeneity of rheumatoid arthritis].
AB  - The diagnostic category of rheumatoid arthritis, a syndrome of chronic
      inflammatory disease of the synovial membrane and of extraarticular tissues,
      covers a broad spectrum of clinical phenotypes. Here we propose that distinct
      combinations of disease risk genes produce heterogeneity of rheumatoid disease.
      Recognition of this genetic and clinical heterogeneity has immediate implications
      as it provides the opportunity to develop selective therapies for the different
      variants of disease.

PMID- 11227381
TI  - [The role of angiogenesis in rheumatoid arthritis].
AB  - The paper presents recent data on the angiogenesis and the angiogenic and
      angiostatic mediators in rheumatoid arthritis.

PMID- 11227382
TI  - [Theophylline--contemporary views on cellular mechanism of action].
AB  - Theophylline has been used in the treatment of obstructive pulmonary diseases
      since 30s. However, its mechanism of action is still poorly defined. Up to now,
      its several different actions on the cellular levels are known or hypothesised
      including most important--inhibition of phosphodiesterase isoenzymes and
      antagonism of adenosine, as well as enhancement of catecholamine secretion and
      modulation of calcium ions fluxes. Author reviews all of the proposed theories,
      outlining existing arguments for and against.

PMID- 11227383
TI  - [The role of cysteine protease and cystatin in pathogenesis and laboratory
      diagnosis of periodontal disease].
AB  - The paper presents a review of results concerning the role of host cysteine
      proteases, especially cathepsin B and cystatins in periodontal pathogenesis.
      Special attention was paid to the potential use of those biochemical parameters
      as biomarkers of periodontal disease activity.

PMID- 11227384
TI  - [N-terminal atrial natriuretic peptides].
AB  - Atrial myocytes synthesise atrial natriuretic factor prohormone consisting of 126
      amino acids (ANP1-126) which is subsequently processed to several fragments.
      Atrial natriuretic factor (ANF, ANP99-126) originating from the C-terminal
      portion of prohormone is a best described atrial peptide. However, several
      peptides originating from the N-terminus of this precursor also circulate and
      produce significant diuresis, natriuresis and vasodilatation. These are: long
      acting natriuretic peptide (ANP1-30), vessel dilator (ANP31-67) and kaliuretic
      peptide (ANP79-98). ANP1-98 and ANP68-98 also circulate. Kaliuretic peptide
      specifically stimulates urinary potassium excretion. These peptides are slowly
      metabolised and their plasma concentration is higher than ANF suggesting their
      important role in water-electrolyte homeostasis and regulation of vascular tone.
      N-terminal atrial peptides don't bind to classical natriuretic peptide receptors,
      each of them has probably its own unique receptors. Although these peptides
      activate particulate guanylate cyclase in a number of tissues, some of their
      effects, for example natriuresis, are not mediated by cGMP but rather by
      prostaglandin E2. Plasma concentration of N-terminal atrial peptides may be
      useful in diagnosis and risk stratification in patients with heart failure and
      after myocardial infarction. Recently N-terminal fragment of brain natriuretic
      peptide (BNP1-76) was identified in the blood. This peptide is secreted together
      with its C-terminal partner, BNP77-108 by ventricular myocytes. Some studies
      suggest that N-terminal BNP may be also a useful diagnostic tool in
      cardiovascular diseases.

PMID- 11227385
TI  - Familial occurrence of pigment dispersion syndrome.
AB  - BACKGROUND: Pigment dispersion syndrome affects up to 4% of the white population.
      It is characterized by the presence of transillumination defects, Krukenberg's
      spindle and dense trabecular meshwork pigmentation. Open-angle glaucoma will
      develop in as many as 50% of affected patients. In this study we describe the
      familial occurrence of pigment dispersion syndrome in six North American
      pedigrees and the phenotypic characteristics with respect to pigment dispersion
      syndrome and glaucoma. METHODS: Probands with pigment dispersion syndrome were
      identified in glaucoma clinics at university eye centres in Ottawa and Durham,
      NC. Families with two or more affected members were evaluated. All willing
      members in each family underwent a thorough clinical examination and were
      classified as affected with pigment dispersion syndrome, suspect or unaffected.
      The previous medical records were reviewed to obtain the past medical and ocular
      history, including risk factors for glaucoma. RESULTS: All six families are
      white. Three families show at least two generations of affected members. Of the
      43 subjects examined 58% were women. All 14 affected members showed moderate to
      heavy trabecular meshwork pigmentation and either Krukenberg's spindle or
      transillumination defects. The affected members were also considerably more
      myopic (mean spherical equivalent for the right eye -4.72 dioptres) than the
      suspect group or the unaffected group (mean spherical equivalent -0.79 D and
      +1.19 D respectively) (p < or = 0.001), and the intraocular pressure was higher
      for the affected than the unaffected group (mean for the right eye 20 mm Hg vs.
      16 mm Hg) (p = 0.004). Half of those affected also had open-angle glaucoma.
      INTERPRETATION: We have identified and phenotypically characterized six North
      American families with autosomal dominant pigment dispersion syndrome. Our
      ultimate goal is to identify the gene(s) that causes this disorder in order to
      clarify its molecular etiology and pathophysiology. This may give rise to a
      molecular classification of the disease as well as provide the foundation for
      genetic testing and new treatment approaches.

PMID- 11227386
TI  - Vertical rectus muscle transposition and botulinum toxin for complete sixth nerve
      palsy.
AB  - BACKGROUND: Effective surgical treatment of complete unrecovered sixth nerve
      palsy must include the transfer of abducting power to the temporal aspect of the
      globe with release of medial rectus contracture nasally. We describe our
      experience in the treatment of five such patients who underwent full vertical
      rectus transposition combined with botulinum toxin chemodenervation of the
      ipsilateral medial rectus muscle. METHODS: The five patients all had primarily
      unilateral complete unrecovered sixth nerve palsy. They all underwent a complete
      preoperative and postoperative eye examination and an orthoptic assessment.
      Excursion into abduction was graded from -8 (globe immobilized in extreme
      adduction) to -4 (abduction as far as primary position) to 0 (full abduction).
      Abduction saccades and a forced muscle generation test confirmed the presence of
      complete unrecovered sixth nerve palsy, and forced duction testing measured the
      degree of medial rectus contracture. All patients received ipsilateral medial
      rectus injection of botulinum toxin in the preoperative (8 to 2 months before
      surgery) and perioperative periods, and underwent complete superior rectus
      inferior rectus transposition temporally. RESULTS: The average length of follow
      up was 21 (range 6 to 48) months. The average preoperative distance alignment was
      52 (range 25 to 80) prism dioptres (PD). Vertical rectus transposition combined
      with botulinum toxin injection resulted in an average distance alignment change
      of 66 PD (range 50 PD to 82 PD) of exoshift. The average final deviation was 1 PD
      of esotropia (range 4 PD of esotropia to 6 PD of exotropia). Average abduction
      improved from -6 (range -3 to -8) preoperatively to -1.7 (range -1 to -2)
      postoperatively. Saccades averaged -4 preoperatively and improved to -2
      postoperatively. Normal vertical eye movements were preserved in all patients. A
      total field of single binocular vision was created in all patients, which
      averaged 55 degrees (range 30 degrees to 75 degrees) in the horizontal meridian.
      The field of single binocular vision from primary position into abduction
      averaged 23 degrees (range 18 degrees to 28 degrees). INTERPRETATION: Temporal
      transposition of the vertical rectus muscles combined with perioperative
      botulinum toxin injection of the ipsilateral medial rectus muscle is a reliable
      and effective way of restoring functional binocular vision in patients with
      complete unrecovered sixth nerve palsy.

PMID- 11227387
TI  - Myasthenia gravis with ocular involvement in older patients.
AB  - BACKGROUND: There has been little previous study reporting the eye findings and
      presentation of elderly patients with myasthenia gravis. The purpose of this
      study was to review the findings and course of myasthenia gravis after the sixth
      decade of life. METHODS: Retrospective observational case series. The authors
      reviewed the clinical records of 27 patients with onset of myasthenia gravis at
      age 60 years or more who were seen at a tertiary care academic ophthalmology
      centre in Houston between January 1992 and March 1999. The diagnosis of
      myasthenia gravis was based on conventional clinical and laboratory criteria.
      RESULTS: Twenty patients (74%) were men. Of the 16 patients who underwent testing
      for anti-acetylcholine receptor antibodies, 11 (69%) were seropositive.
      Concurrent thyroid disease was found in seven patients (26%), including five
      (71%) of the seven women. No patient had thymoma. Sixteen patients (59%)
      manifested generalized symptoms during follow-up; 12 did so within 1 year of
      disease onset. Patients responded well to both anticholinesterase and
      corticosteroid therapy. At the most recent follow-up visit 18 patients (67%) were
      clinically improved, and no patient was clinically worse. INTERPRETATION:
      Myasthenia gravis in this study was characterized by a male predominance, high
      rate of concurrent thyroid disease, high rate of progression to mild generalized
      symptoms, absence of thymoma, good response to medical therapy and minimal life
      threatening complications. Clinicians should consider the diagnosis of myasthenia
      gravis in an older patient presenting with diplopia or ptosis.

PMID- 11227388
TI  - Bilateral retinal arteriolar occlusion secondary to OKT3 therapy.

PMID- 11227389
TI  - Central retinal vein occlusion after trabeculectomy with mitomycin C.

PMID- 11227390
TI  - Ignacio Barraquer (1884-1965) and the Barraquer family of ophthalmologists.

PMID- 11227391
TI  - Update in retina: photodynamic therapy for the treatment of subfoveal choroidal
      neovascularization secondary to age-related macular degeneration.

PMID- 11227392
TI  - The single market for pharmaceuticals in the European Union in light of European
      Court of Justice rulings.
AB  - This article analyses the likely implications for the European pharmaceutical
      market of 2 European Court rulings (Kohll and Decker) and addresses whether these
      will contribute to the completion of the single European market. In doing so, the
      Kohll and Decker cases are discussed and the likely implications of these cases
      for key stakeholders (patients, providers, payers and the industry) are
      investigated. Of the 2 cases, the latter has direct application to
      pharmaceuticals as tradable goods. The article argues that the short term
      implications for the stakeholders, relating to the freedom of providing goods,
      may lead to a re-thinking of how pharmaceutical products are financed and
      provided in European Union (EU) countries in the long term. A key corollary of
      the Decker case is that it leads to greater transparency and awareness of
      pharmaceutical price differentials across the member states. As part of this
      transparency, consumers may benefit directly by gaining access to a product that
      may not be available in their country of residence, or may be available but at a
      higher cost. Consumers may also benefit indirectly through greater transparency
      and efficiency in the long term. Providers may wish to increase their procurement
      from cheaper sources of the same product and much will depend on their future
      procurement strategies. Manufacturers will in this case face an increase in
      parallel trade streams and may respond by not marketing or producing in 'low
      price' countries. The rulings add a further supranational dimension to a national
      policy issue and may have far reaching implications for the EU pharmaceutical
      market and industry.

PMID- 11227393
TI  - Stratified administration of serotonin 5-HT3 receptor antagonists (setrons) for
      chemotherapy-induced emesis. Economic implications.
AB  - The serotonin 5-HT3 receptor antagonists or 'setrons' have become the standard of
      care for the prevention of chemotherapy-induced emesis (CIE) and are first-line
      therapy for acute CIE in healthcare organisations worldwide. However, their
      superior efficacy versus standard antiemetics comes at a significant cost.
      Currently, 3 agents are available in the US: ondansetron, granisetron and
      dolasetron. The most important treatment-related factor contributing to CIE is
      the emetogenicity of chemotherapy. The ability to customise, or stratify, the
      setron dose to match the emetogenic challenge of the chemotherapy administered
      has potential benefits, both clinically and economically. In adults, there is an
      appreciable amount of clinical literature addressing stratified administration;
      however, the amount of 'hard' economic data is rather limited. Intuitively, if
      clinical outcomes are equivalent, then stratified administration should be
      associated with economic benefits, as it generally promotes the use of doses
      lower than those recommended by the manufacturer. The literature strongly
      substantiates this for ondansetron, but is not as favourable for granisetron or
      dolasetron. As the rationale and justification for dose stratification is
      contained in the clinical literature, the authors have reviewed the pertinent
      literature supporting the clinical and economic benefits of dose stratification
      in both adult and paediatric patients. The authors also provide a discussion of
      various additional strategies that can be employed to ensure the appropriate and
      cost-effective use of setrons in real-world practice settings. These strategies
      include the use of lower doses than recommended by manufacturers, use for acute
      versus delayed phase emesis, enhancing the antiemetic efficacy by the addition of
      a corticosteroid, use of oral versus injectable formulations (when appropriate)
      and the implementation and use of local, national and international drug use
      guidelines.

PMID- 11227394
TI  - Effectiveness of eletriptan in reducing time loss caused by migraine attacks.
AB  - BACKGROUND: The growing literature on the economics of migraine and its treatment
      generally indicates that the direct healthcare costs of managing the disorder are
      relatively low compared with the personal and societal burdens resulting from the
      disruption to normal functioning caused by migraine attacks. OBJECTIVE: To
      investigate the effectiveness of eletriptan, a new selective serotonin (5
      hydroxytryptamine; 5-HT)5-HTIB/ID agonist, in reducing both the patient-focused
      burden of migraine and the amount of work time foregone during a single attack.
      DESIGN: In a phase III, multinational, randomised clinical trial, 692 patients
      treated a migraine attack with eletriptan 40 mg or 80 mg, or placebo. Patients
      responded to a questionnaire seeking information concerning the amount of time
      lost from usual activities during the attack. Time loss assessments were made 24
      hours after the last dose taken and recorded in a diary. MAIN OUTCOME MEASURES
      AND RESULTS: Patients receiving either dose of the active compound were unable to
      perform their usual activities for a median period of 4 hours compared with 9
      hours experienced by those taking placebo. This difference was highly
      statistically significant (p < 0.001). The time saving associated with eletriptan
      usage reflected the differences in efficacy findings in the clinical component of
      the study. CONCLUSION: In this placebo-controlled trial, eletriptan produced a
      significant reduction in the loss of usual functioning time associated with a
      migraine attack. This gain clearly represents a substantial benefit to patients
      with migraine irrespective of how it might most appropriately be valued in
      monetary terms. Further methodological progress in this area is warranted.

PMID- 11227395
TI  - Olanzapine versus risperidone. A prospective comparison of clinical and economic
      outcomes in schizophrenia.
AB  - OBJECTIVE: To compare the clinical and economic outcomes associated with
      olanzapine and risperidone treatment for schizophrenia. DESIGN AND SETTING: An
      international, multicentre, double-blind, prospective study. To facilitate
      economic comparisons, our sample was restricted to patients enrolled in US sites.
      150 patients with a Diagnostic and Statistical Manual of mental disorders, 4th
      edition (DSM-IV) diagnosis of schizophrenia, schizoaffective disorder or
      schizophreniform disorder were randomised to therapy with either olanzapine 10 to
      20 mg/day (n = 75) or risperidone 4 to 12 mg/day (n = 75) for a maximum of 28
      weeks. In addition to tolerability and efficacy assessments, use of health
      services was assessed at baseline and prospectively, at 8-week intervals and at
      study completion. Clinically important response, defined as a 40% improvement in
      the Positive and Negative Syndrome Scale total score, maintenance of response and
      rates of treatment-emergent extrapyramidal symptoms were compared between groups.
      Direct medical costs were estimated by assigning standardised prices to resource
      units. Median total, inpatient/outpatient service and medication acquisition
      costs were compared between treatment groups. MAIN OUTCOME MEASURES AND RESULTS:
      The mean modal dosages for the olanzapine and risperidone treatment groups were
      17.7 +/- 3.4 mg/day and 7.9 +/- 3.2 mg/day, respectively. Olanzapine-treated
      patients were more likely to maintain response compared with risperidone-treated
      patients (p = 0.048). In addition, a smaller proportion of olanzapine-treated
      patients required anticholinergic therapy compared with risperidone-treated
      patients (25.3 vs 45.3%; p = 0.016). Total per patient medical costs over the
      study interval were $US2843 (1997 values) [36%] lower in the olanzapine treatment
      group than in the risperidone treatment group (p = 0.342). Medication costs were
      significantly higher for olanzapine-treated patients ($US2513 vs $US1581; p <
      0.001), but this difference was offset by a reduction of $US3774 (52%) in
      inpatient/outpatient service costs for olanzapine-treated patients in comparison
      with risperidone-treated patients ($US3516 vs $US7291, p = 0.083). Median cost
      findings were consistent with results observed using other robust measures of
      central tendency and provide conservative estimates of potential savings that may
      be obtained from olanzapine therapy. CONCLUSIONS: In this study, olanzapine
      treated patients experienced clinical improvements that translated into savings
      in costs of care for both inpatient and outpatient services. These savings offset
      the difference in medication acquisition cost between olanzapine and risperidone.

PMID- 11227396
TI  - Association between abciximab and length of stay in intensive care for patients
      undergoing percutaneous coronary intervention. A 2-stage econometric model in a
      naturalistic setting.
AB  - OBJECTIVE: To examine the effect of abciximab treatment on intensive care length
      of stay for patients undergoing percutaneous coronary intervention (PCI). DESIGN
      AND SETTING: A retrospective study conducted in a naturalistic setting. METHODS:
      A 2-stage econometric model was used to control for the influence of possible
      selection bias across categories of patients and for both observable and
      unobservable factors correlated with each patient's treatment selection and
      length of stay in intensive care. Multivariate analysis was applied to control
      for a wide range of factors (patient demographics, insurance provider, health
      conditions, admission and discharge information, and hospital characteristics)
      that may influence intensive care length of stay. Retrospective data were
      obtained from HCIA's Clinical Pathways Database. PARTICIPANTS: Patients (n =
      13,364) who were hospitalised in any of 87 hospitals across the US over the
      period from October 1, 1995 to December 1, 1996. RESULTS: After controlling for
      high-risk indications and selection bias, results indicated that administration
      of abciximab was associated with a significantly shorter length of stay in
      intensive care compared with not administering a GPIIb/IIIa inhibitor (0.45 fewer
      days; p < or = 0.0001). In a subgroup analysis of patients having an acute
      myocardial infarction (n = 4793), administration of abciximab was also associated
      with a significantly shorter intensive care stay (0.27 fewer days; p < 0.0001).
      CONCLUSION: Results of this study indicate that the administration of abciximab
      is associated with a reduction in the length of stay in intensive care. This
      reduction implies potential cost offsets for patients undergoing PCI who receive
      abciximab.

PMID- 11227398
TI  - Potential savings in the cost of caring for Alzheimer's disease. Treatment with
      rivastigmine.

PMID- 11227397
TI  - Inhaled salmeterol/fluticasone propionate combination. A pharmacoeconomic review
      of its use in the management of asthma.
AB  - Cost estimates from developed countries indicate that asthma accounts for up to
      2% of the economic cost of all diseases. A large proportion of asthma-related
      costs are attributable to poor asthma control. Treatment strategies which improve
      clinical outcomes in patients with asthma, therefore, have the potential for
      significant economic benefits, and it is important to evaluate new asthma
      therapies for cost effectiveness. Several studies have established that
      salmeterol and fluticasone propionate combined in a single dry powder inhalation
      device are at least as effective as a combination of the 2 drugs administered via
      separate dry powder inhalers and more effective than monotherapy with fluticasone
      propionate or budesonide. Importantly, pharmacoeconomic analysis of several of
      these studies show that the salmeterol/fluticasone propionate combination is cost
      effective relative to monotherapy with fluticasone propionate or budesonide.
      Although the total cost of asthma management tended to be slightly higher with
      salmeterol/fluticasone propionate than with inhaled corticosteroid monotherapy,
      in most cases mean cost-effectiveness ratios were lower (i.e. more favourable)
      for salmeterol/fluticasone propionate than either fluticasone propionate or
      budesonide. Cost effectiveness was assessed according to 3 end-points:
      successfully treated weeks, symptom-free days and episode-free days. Mean cost
      effectiveness ratios consistently favoured salmeterol/fluticasone propionate over
      the comparator drug for the end-point successfully treated weeks, and in most
      cases the other 2 end-points also favoured the combination product over the
      comparator. In a further study, salmeterol/fluticasone was also less costly than
      therapy with formoterol and budesonide administered via 2 separate inhalers.
      Studies of health-related quality of life (HR-QOL) using the Asthma Quality of
      Life Questionnaire indicate that salmeterol/fluticasone propionate produces
      clinically meaningful improvements in overall HR-QOL relative to salmeterol
      monotherapy or placebo. Improvements in overall HR-QOL were statistically
      significantly greater for salmeterol/fluticasone propionate than with fluticasone
      propionate or budesonide alone, although the differences between treatments did
      not exceed the threshold for clinical significance. In conclusion, short term
      cost-effectiveness data show that salmeterol/fluticasone propionate is more cost
      effective than the inhaled corticosteroids budesonide and fluticasone propionate
      alone. The combination product also appears to improve HR-QOL relative to placebo
      or salmeterol alone.

PMID- 11227400
TI  - [BSE tests are negative in 17,000 cows].

PMID- 11227399
TI  - [Streptococcus gallolyticus infections in racing pigeons, a literature review].
AB  - S. gallolyticus, formerly known as S. bovis is known since 1988 as a facultative
      pathogen of racing pigeons. Important clinical signs include acute mortality,
      inability to fly, lameness, weight loss and slimy green diarrhea. A pathognomonic
      sign at post mortem examination is the presence of well circumscribed areas of
      necrosis in the pectoral muscle. Furthermore tenosynovitis of the supracoracoid
      muscle and arthritis of the knee, shoulder and hock can be observed. In one study
      S. gallolyticus septicaemia was diagnosed in 10% of necropsied pigeons. Since S.
      gallolyticus was also isolated from nearly 40% of clinical healthy pigeons it is
      regarded as a facultative pathogen. Various biotypes, serotypes and culture
      supernatant phenotypes can be distinguished. Supernatant phenotypes are
      identified on the basis of the presence of either a T1, T2 or T3 protein triplet
      and the presence or absence of an extracellular A protein. S. gallolyticus
      strains with A protein are highly virulent, while strains with only T3 or T2
      protein are of moderately or low virulence respectively. Fimbriae are only seen
      in highly virulent and some of the moderately virulent strains. Possible
      virulence factors include survival in macrophages, adhesion to cells and toxin
      production. Infection with serotype 1 and 2 induces some degree of protection
      against re-infection with serotype 1, which offers perspectives for the
      development of a vaccine. Experimentally ampicillin, doxycycline and erythromycin
      have shown therapeutic effects. For the treatment of clinical cases the use of
      ampicillin is advocated, together with hygienic measures, such as the use of grid
      floors and avoiding overcrowding.

PMID- 11227401
TI  - [Passports, logbooks and participation in horse races].

PMID- 11227402
TI  - [Immuno-castration and decision making: a question of integrity].

PMID- 11227403
TI  - [Animal integrity].

PMID- 11227404
TI  - [Developments by pharmaceutical companies].

PMID- 11227405
TI  - [Brooke hospital for animals: a visit to a clinic in Lahore, Pakistan].

PMID- 11227406
TI  - [Marketing is not a dirty word: everyone does it!].

PMID- 11227407
TI  - [Second meeting of Overijssels new(s)].

PMID- 11227408
TI  - [Veterinarians for small animals choose permanent education].

PMID- 11227409
TI  - Hydrazine reagents as derivatizing agents in environmental analysis--a critical
      review.
AB  - Hydrazine reagents are a well-known group of derivatizing agents for the
      determination of aldehydes and ketones in liquid and gaseous samples. Within this
      article, the most important hydrazine reagents are critically summarized, and
      their major applications in different fields, including environmental analysis,
      food chemistry and industrial analysis are introduced. As 2,4
      dinitrophenylhydrazine (DNPH) is the basic reagent for several international
      standard procedures, its properties are discussed in detail. Particular focus is
      directed on the chemistry of the hydrazine reagents, and chemical interferences
      are considered. Recent methods for the determination of various oxidants using
      hydrazine reagents are presented as well. Due to limited space, this review does
      not cover the related field of carbohydrate analysis, although many chemical
      aspects are similar.

PMID- 11227410
TI  - Certification of trace and major elements and methylmercury concentrations in a
      macroalgae (Fucus sp.) reference material, IAEA-140.
AB  - A marine reference material, IAEA-140, prepared with a macroalgae (Fucus sp.) was
      recently produced by the International Atomic Energy Agency and certified for
      trace and major elements and for methylmercury (MeHg). Certification of this
      material was achieved as an outcome of an international analytical
      intercomparison study which resulted in 116 independent sets of results reported
      by participants from 54 countries. The statistical evaluation of the collected
      data and the criteria used for assignment of the mean and uncertainty values are
      described. The analysis of data allowed to certify concentration values for 24
      elements and MeHg, and to provide information values for another 10 elements.
      Regarding the elements which could be given certified values, between two and
      eight different instrumental methods were used to measure metal concentrations,
      and four independent analytical procedures were used to measure MeHg
      concentrations. In order to assess the results of the certification procedure, a
      comparison was made between the certified values obtained from the world-wide
      intercomparison results and the values obtained from a small subgroup of well
      qualified laboratories. The means and 95% confidence intervals for reference
      values obtained by the two methods are similar for most elements showing that the
      usual method of certification used by the IAEA, based on large groups of
      participants, is indeed pertinent.

PMID- 11227411
TI  - Quality control of automotive engine oils with mass-sensitive chemical sensors-
      QCMs and molecularly imprinted polymers.
AB  - Molecularly imprinted polyurethanes were used as sensor materials for monitoring
      the degradation of automotive engine oils. Imprinting with characteristic oils
      permits the analysis of these complex mixtures without accurately knowing their
      composition. Mass-sensitive quartz crystal microbalances (QCMs) coated with such
      layers exhibit mass effects in addition to frequency shifts caused by viscosity,
      which can be compensated by an uncoated quartz or a non-imprint layer.
      Incorporation of degradation products into the imprinted coatings is a bulk
      phenomenon, which is proven by variation of the sensor layer height. Therefore,
      the resulting sensor effects are determined by the degradation products in the
      oil.

PMID- 11227412
TI  - Polyaniline-coated microtiter plates for use in longwave optical bioassays.
AB  - A technique for coating the wells of microtiter-plates with polyaniline layers
      and with polyaniline/enzyme layers is presented. The resulting wells are shown to
      be useful for assaying enzyme substrates (as exemplified for glucose via pH) and
      hydrogen peroxide (via the redox properties of the film). Analyte detection is
      based on monitoring the absorption spectra of the polyaniline, which turn purple
      as a result of redox processes, or green on formation of acids by enzymatic
      reactions. Hydrogen peroxide (a species produced by all oxidases) and glucose
      (which yields protons on enzymatic oxidation) have been determined in the
      millimolar to micromolar concentration range. High sensitivity, film stability
      and good reproducibility of the measurements make the system an attractive
      alternative to existing biosensing schemes.

PMID- 11227413
TI  - A new procedure for the construction of flow-through optodes. Application to
      determination of copper (II).
AB  - A new procedure for constructing an optical fibre reflectance, bulk optode
      membrane type, sensor is presented. The optode membrane consists of a plasticized
      poly (vinyl chloride) membrane in which the ionophore is dissolved, entrapped in
      a cellulose support. The new optode with the dye indicator 1-(2-pyridylazo)-2
      naphthol (PAN) was incorporated in a new flow-through cell and the injection
      system was optimized to determine Cu (II) at 567 nm in the range 5 x 10(-5)-10(
      3) M. The response was reproducible and the optode can be regenerated using 10(
      2) M EDTA followed by water. The method was applied to the determination of
      copper in real samples.

PMID- 11227414
TI  - Synthesis of rhodanine-bonded silica gel and its application in the
      preconcentration and separation of noble metals.
AB  - A silica gel based sorbent containing rhodanine as functional group (RDSG) was
      prepared. Its adsorption and separation characteristics for Ag(I), Au(III) and
      Pd(II) were studied by flow-injection (FI) on-line preconcentration. Influence of
      different experimental parameters such as acidity, eluent, co-existing ions were
      investigated. Trace amounts of Ag, Au and Pd could be efficiently adsorbed by
      rhodanine-bonded silica gel from acidic solution and eluted with thiourea
      solution. Common co-existing ions exhibited virtually no interference to the
      preconcentration and determination. The adsorption capacity of RDSG was 0.0352,
      0.107 and 0.122 mmol/g for Ag, Au and Pd, respectively. Detection limits of
      0.004, 0.022 and 0.019 microg/mL for Ag, Au and Pd, respectively, were achieved
      with a sampling time of 60 s at a flow rate of 5.0 mL/min. The relative standard
      deviation were 0.5%, 0.9% and 1.7% for 0.040 microg/mL Ag, 0.200 microg/mL Au and
      0.300 microg/mL Pd. The sorption property did not change after 1,000 cycles of
      sorption-desorption. The contents of Ag and Au in three national certified ore
      samples and Pd in a secondary nickel alloy, an anode slime and a CoCl2
      electrolytic solution were determined. The results showed good agreement with the
      certified values.

PMID- 11227415
TI  - Application of an imidazoline group-containing chelating fiber for the
      determination of trace noble metals in superhigh-temperature alloys.
AB  - An imidazoline group-containing chelating fiber was prepared by means of the
      reaction of nitrile groups with ethylenediamine in an hydrazine-modified
      polyacrylonitrile fiber. The adsorption properties of the chelating fiber for
      Au(III), Pd(II), Pt(IV), Ir(IV), Os(IV), Rh(III) and Ru(IV) ions, such as binding
      capacity, distribution coefficient, sorptive rate and quantitative elution of
      Au(III), Pd(II) and Pt(IV) ions were investigated. The imidazoline group
      containing chelating fiber possessed high binding capacities and good adsorption
      kinetic properties, exhibited high affinity for noble metals in 0.1-1.0 mol/L HCl
      and could be efficiently re-used. After the separation of trace Au(III), Pd(II)
      and Pt(IV) ions from a matrix using the chelating fiber, these ions could be
      determined by ICP-AES with satisfactory results, and the relative standard
      deviation for Au(III), Pd(II) and Pt(IV) ions was less than 6%.

PMID- 11227416
TI  - Rapid and selective determination of ammonium by fluorimetric flow injection
      analysis.
AB  - Selective and sensitive procedures for the determination of ammonium in river
      water and diluted urine were developed by using flow injection analysis
      equipment. The methods are based on the derivatization of ammonia with o
      phthaldehyde (OPA) and thioglycolate under alkaline conditions. The formed
      isoindole derivative is detected fluorimetrically at an excitation wavelength of
      415 nm and an emission wavelength of 485 nm. The derivatization only takes 15 to
      20 s at room temperature to achieve the maximum sensitivity. The optimized OPA
      reagent shows a surprisingly high selectivity for ammonium in the presence of
      many primary amines. With respect to the analysis of turbid and fluorescent
      sample solutions the selectivity can be improved by separating the ammonia
      through a microporous membrane from the OPA reagent. Without this separation step
      ammonia can be detected in the range between 0.05 and 100 microM with excellent
      linearity. After the insertion of an optimized membrane separation cell ammonia
      can be determined in the linear range between 0.2 microM and 20 mM.

PMID- 11227417
TI  - Speciation of arsenic in coarse and fine urban aerosols using sequential
      extraction combined with liquid chromatography and atomic fluorescence detection.
AB  - An analytical procedure for speciation of As in urban aerosol samples was
      developed. The aerosols were collected by sequential filtration through membrane
      filters. Part of each filter was investigated by INAA for the total amount of As.
      Another part of the filters was treated by a sequential extraction procedure to
      differentiate between water-extractable, phosphate-extractable and refractory
      chemical forms. Water-extractable forms were further differentiated into anionic
      As species by HPLC-HGAFS. Extractability of As into water exhibited a clear
      dependency on the aerosol size fraction (12% in coarse fraction and 50% in fine
      fraction). Dependency of the phosphate extractable As on the aerosol size
      fraction seems not to be significant (10-15% in both size fractions). The
      remaining amount, i.e., about 78% of the coarse As and about 40% of the fine As
      was considered to be refractory or environmentally immobile As. Water-extractable
      As forms could only be attributed to arsenate.

PMID- 11227418
TI  - A sensitive method for the determination of iodine containing diagnostic agents
      in aqueous matrices using LC-electrospray-tandem-MS detection.
AB  - Iodinated contrast media belong to the most frequently applied compounds in
      medicine. They exhibit a high polarity and are very persistent against metabolism
      by the organism and environmental degradation. A sensitive method for the
      determination of five iodinated contrast media in aqueous matrices is described.
      Solid phase extraction utilizing Isolute ENV+ material was used for sample
      enrichment. The contrast media were partially separated on a RP-C18 column, and
      detection was achieved using electrospray-tandem MS (API III plus and API 365)
      allowing the sensitive quantitation of these compounds down to the lower ng/L
      range. The recovery rates generally exceeded 70%, for spiked surface water as
      well as tap water. The analytes were detected in native samples such as municipal
      sewage treatment plant (STP) effluent, the river Rhine and even in tap water.

PMID- 11227419
TI  - Flame atomic absorption spectrometric determination of lead in waste water and
      effluent after preconcentration using a rapid coprecipitation technique with
      gallium phosphate.
AB  - A determination method for lead in waste water and effluent was studied using
      flame atomic absorption spectrometry after preconcentration of lead by the rapid
      coprecipitation technique with gallium phosphate. Lead ranging from 0.5 to 50
      microg was quantitatively coprecipitated with gallium phosphate from 100-150 mL
      sample solution (pH approximately 5). The presence of gallium phosphate did not
      affect the atomic absorbance of lead. Since the concentration of gallium in the
      final sample solution is also measurable by flame atomic absorption spectrometry
      at 250.0 nm without further dilution, the rapid coprecipitation technique, which
      does not require complete collection of the precipitate, becomes possible using a
      known amount of gallium and measuring the concentrations of both lead and gallium
      in the final sample solution by flame atomic absorption spectrometry. The 32
      diverse ions tested gave no significant interferences in the lead determination.
      The method proposed here is rapid and has good reproducibility.

PMID- 11227420
TI  - Determination of polycyclic aromatic hydrocarbons in marine sediments using a new
      ASE-SFE extraction technique.
AB  - In order to determine PAHs in marine sediment samples by GC/MS(SIM) a new
      extraction approach of ASE-SFE was evaluated using combined accelerated solvent
      extraction (ASE, dynamic and static mode) and supercritical fluid extraction
      (SFE, dynamic mode) without further purification of the sample. The solvents used
      for ASE-SFE were methylene chloride and carbon dioxide. The recovery data,
      precision and accuracy of the whole method were evaluated statistically. The
      average recoveries of PAHs, based on deuterated internal standards were 77% for 2
      3-ring PAHs, 85% for 4-ring PAHs, 88% for 5-ring PAHs and 97% for 6-ring PAHs.
      The extraction time required for the ASE-SFE technique was 30 min, which is
      longer than in the case of independent use of ASE and shorter compared to SFE.
      ASE-SFE recoveries of PAHs from SRM marine sediment are comparable for (2-3-ring,
      4-ring PAHs) or higher (5-ring, 6-ring PAHs) than reported for the conventional
      extraction methods of ASE and SFE. Method detection limits of (MDL) were
      statistically estimated. MDL values obtained for 15 PAHs compounds vary between
      0.06 ngg(-1) and 3.54 ngg(-1).

PMID- 11227421
TI  - Reasons for the decomposition of the fungicide thiram during preparation of fruit
      and vegetable samples and consequences for residue analysis.
AB  - The concentration of thiram in aqueous solution decreases by 50-75% within 20 min
      in the presence of cut pieces of apple, cucumber or celeriac with a section
      surface area of 160 cm2 each. The decomposition rate is predominantly influenced
      by the section surface area of the cut fruit and vegetable samples. Denaturing
      reaction conditions (exchange of the solvent water by methanol; boiling of sample
      material) will significantly slow down the decomposition rate. It was concluded
      that the thiram decomposition had been caused by enzymes on the section surface
      of the fruit and vegetable samples. For a specific determination of thiram, a
      simple rinsing of the intact fruit and vegetable material was appropriate as
      extraction method. For the screening of thiram residues, the often used Keppel
      method, which determines CS2 from thiram or dithiocarbamates seems to be
      applicable even if samples had been coarsely cut, since decomposition of the CS2
      forming intermediates is slower than the breakdown of thiram itself. Therefore,
      specific determination of thiram is necessary only, if maximum residue limits for
      dithiocarbamates are not adhered to.

PMID- 11227422
TI  - Flow injection spectrophotometric determination of ascorbic acid in soft drinks
      and beer.
AB  - Two spectrophotometric methods, a photochemical and a non-photochemical, for the
      determination of ascorbic acid in soft drinks and beer using a flow-injection
      system are proposed. The non-photochemical method is based on the redox reaction
      that takes place between ascorbic acid and Fe(III), yielding dehydroascorbic acid
      and Fe(II). Fe(II) reacts with 1,10-phenantroline, originating the reddish orange
      Fe(phen)3(2+) complex (ferroin). This complex is spectrophotometrically monitored
      at 512 nm, and the signal is directly related to the concentration of ascorbic
      acid in the sample. The photochemical method has the same basis, nevertheless,
      uses the irradiation with visible light to enhance the redox reaction and so
      achieve higher sensitivities in the analysis. The non-photochemical method shows
      a linear range between 5 and 80 microg mL(-1), with a relative standard deviation
      of 1.6% (n = 11), a detection limit of 2.7 microg mL(-1) and a sample throughput
      of 60 samples h(-1). The photochemical method shows a linear range between 1 and
      80 microg mL(-1), with a relative standard deviation of 1.0% (n = 11 ), a
      detection limit of 0.5 microg mL(-1) and a sample throughput of 40 samples h(-1).

PMID- 11227423
TI  - Determination of proteins at nanogram levels by their quenching effect on large
      particle scattering of colloidal silver chloride.
AB  - A novel quantitative method for the determination of proteins in aqueous
      solutions has been based on the quenching of the resonance scattering light of
      colloidal silver chloride in the presence of proteins. The detection limits for
      eight kinds of proteins (BSA, HSA, egg albumin, human gamma-IgG,alpha
      chymotrypsin, E. Coli. alpsase, myoglobin, alpha-casein) were at about 8 ng/mL;
      the linear ranges of the calibration curves were 10-400 ng/mL under optimal
      conditions,except for human gamma-IgG (20-400 ng/mL), myoglobin (10-300 ng/mL),
      and alpha-casein (10-300 ng/mL). Three wavelengths (398 nm, 475 nm, 499 nm) were
      all suitable for the determination and any acidity from pH 3.0 to pH 9.0 could be
      chosen. A few non-protein substances at high concentration levels interfered with
      this method, but this problem could simply be overcome by diluting the samples
      before the assay. Mechanism studies showed that the quenching effect of proteins
      on the scattering light of colloidal silver chloride was mainly due to the
      coagulation of AgCl particles retarded by protein. The method was employed for
      the determination of total protein in human serum with satisfactory results.

PMID- 11227424
TI  - Selectively conjugated melittins for liposome time-resolved fluoroimmunoassay of
      theophylline in serum.
AB  - Theophylline (Th) has been selectively conjugated to the four amino groups of
      melittin (Mel) by solid phase peptide synthesis. The cytolytic activity of the
      resultant Th-Mel compounds was tested on liposomes trapping the bovine serum
      albumin (BSA) conjugate with 4,7-bis(chlorosulfophenyl)-1,10-phenanthrol ine-2,9
      dicarboxylic acid (BCPDA). The loss of lytic activity was the highest for Th-K7
      Mel. Th-G1-Mel retains almost the same lytic activity as Mel. A homogeneous
      liposome time-resolved fluoroimmunoassay (LITRFIA) of Th in serum has been
      carried out with Th-G1-Mel between 5 ng and 10 microg.

PMID- 11227425
TI  - Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) for
      spatially resolved trace analysis of early-medieval archaeological iron finds.
AB  - The suitability of laser ablation ICP-MS for minor and trace analysis of
      archaeological iron finds, produced by a direct reduction process in a 'bloomery'
      furnace, is reported. The analysis of elemental impurities in the iron can
      provide useful archaeometallurgical information on the production process and the
      provenance of the iron. Since, even after refinement, the iron resulting from
      this process may contain many inclusions (slag, charcoal, holes, etc.), a method
      should be used with sufficient spatial resolution to preclude the inclusions from
      the analysis. The ablation parameters are selected such that ablation craters of
      approx. 100 microm in diameter are obtained. The method is validated with low
      alloy steel and cast iron standard reference materials and by a comparative
      analysis with electron probe microanalysis (EPMA). The precision is limited
      mainly by the homogeneity of the iron, rather than by instrumental
      reproducibility. The advantages and drawbacks of the method are briefly compared
      with EPMA. Preliminary results from the analysis of archaeological iron samples
      from excavations at Develier-Courtetelle (Canton Jura, CH), Neftenbach (Canton
      Zurich, CH), Wartau (Canton St Gallen, CH) and Mont Chemin (Canton Valais, CH)
      are given.

PMID- 11227426
TI  - Certification by the Karl Fischer method of the water content in SRM 2890, Water
      Saturated 1-Octanol, and the analysis of associated interlaboratory bias in the
      measurement process.
AB  - The calibration of Karl Fischer instruments and reagents and the compensation for
      instrumental bias are essential to the accurate measurement of trace levels of
      water in organic and inorganic chemicals. A stable, nonhygroscopic standard,
      Water Saturated Octanol, which is compatible with the Karl Fischer reagents, has
      been prepared. This material, Standard Reference Material (SRM) 2890, is
      homogeneous and is certified to contain 39.24 +/- 0.85 mg water/mL (expanded
      uncertainty) of solution (47.3 +/- 1.0 mg water/g solution, expanded uncertainty)
      at 21.5 degrees C. The solubility of water in -octanol has been shown to be
      nearly constant between 10 degrees C and 30 degrees C (i.e., within 1% of the
      value at 21.5 degrees C). The results of an interlaboratory comparison exercise
      illustrate the utility of SRM 2890 in assessing the accuracy and bias of Karl
      Fischer instruments and measurements.

PMID- 11227427
TI  - Comparison of chromium speciation by CZE and ion exchange followed by AAS.
AB  - The hydrogen chromate anion (HCrO4-), which is the predominant species in acidic
      solutions and solutions with low chromium concentration, was determined by
      capillary zone electrophoresis (CZE) using UV detection on-column at 200 nm. A
      fused-silica capillary (55 cm x 50 microm i.d.) was employed with a high negative
      voltage of 20 kV. Total chromium was determined after reduction by H2O2 and its
      complexation by EDTA. The use of H2O2 as reducing agent is advantageous, as it
      does not increase the conductivity of the solution. Detection limits achieved
      (for 200 s injection time) were 30 and 8 microg/L for Cr(VI) and Cr(III),
      respectively. The CZE results obtained for Cr(III) and Cr(VI) were compared with
      those obtained by ion exchange with subsequent AAS.

PMID- 11227428
TI  - Sorption-catalytic determination of cadmium using bromobenzothiazo noncovalently
      bound to silica and paper.
AB  - Cadmium (along with Fe(II), Co(II), Zn(II), and Pb(II) ions) decreases the rate
      of oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) with KIO4 conducted either
      without or with Mn(II) as a catalyst. Cadmium(II) is preconcentrated from aqueous
      solutions on silica plates or paper filters physically modified with a reagent
      for selective determination of Cd(II), namely 1-[(6-bromo-2-benzothiazolyl)azo]-2
      naphthol (bromobenzothiazo, or BBT). The modifier is strongly retained on the
      both supports at pH 6-10 and does not affect the inhibiting effect of Cd(II) in
      the indicator reaction. Cadmium is determined by its inhibiting action directly
      on the sorbents by measuring transmittance (BBT/paper) or reflectance
      (BBT/silica) with limits of detection of 2 x 10(-4) and 0.03 mg/L, respectively.
      The proposed hybrid combination of sorption with catalytic detection on the
      sorbent allows to increase the selectivity factors several times (up to 2 orders)
      relatively to the determination in solution. Tap water samples and soil extracts
      were analyzed.

PMID- 11227429
TI  - Flow injection atomic absorption spectrometric determination of iodide using an
      on-line preconcentration technique.
AB  - A continuous flow atomic absorption spectrometric system was used to develop an
      efficient on-line preconcentration-elution procedure for the determination of
      iodide traces. Chromium (VI) is introduced into the flow system and is reduced to
      chromium (III) in acid medium proportionally to the iodide present in the sample.
      The Cr(III) reduced by iodide is retained on a minicolumn packed with a
      poly(aminophosphonic acid) chelating resin, while unreduced Cr(VI) is not
      retained. Reduced Cr(III) is preconcentrated by passing the sample containing
      iodide through the system during 3 min, and is then eluted with 0.5 mol L(-1)
      hydrochloric acid and determined by flame atomic absorption spectrometry (FAAS).
      The detection limit (3sigma) obtained is 2.5 microg L(-1). Other ions typically
      present in waters do not interfere. The proposed method allows the determination
      of iodide in the range 6-220 microg L(-1) with a relative standard deviation of
      2.7% at a rate of 17 samples h(-1). The method has been applied to the
      determination of iodide in tap and sea waters.

PMID- 11227430
TI  - Microwave assisted extraction of polycyclic aromatic hydrocarbons from
      atmospheric particulate samples.
AB  - For several years, microwave assisted extraction (MAE) was applied to extract
      organic compounds such as polycyclic aromatic hydrocarbons (PAHs),
      polychlorinated biphenyls, etc., from soils, sediments and standard reference
      materials. Very few authors applied this methodology for the extraction of PAHs
      from atmospheric particulate matter. In the present study, MAE of polycyclic
      aromatic hydrocarbons with hexane/acetone (1:1) from real atmospheric particulate
      samples was investigated and the effect of microwave energy and irradiation time
      studied. The yields of extracted compounds obtained by microwave irradiation were
      compared with those obtained using traditional Soxhlet extraction. MAE was
      evaluated using spiked real atmospheric particulate samples and two standard
      reference materials. Analytical determinations of PAHs were carried out by high
      performance liquid chromatography (HPLC) with ultraviolet and fluorescence
      detection. The best recoveries were achieved with a microwave energy of 400 W and
      an irradiation time of 20 min.

PMID- 11227431
TI  - Microwave digestion of "residual fuel oil" (NIST SRM 1634b) for the determination
      of trace elements by inductively coupled plasma-mass spectrometry.
AB  - A microwave procedure for the digestion of the NIST 1634b reference material
      "residual fuel oil" in closed pressurized vessels was developed in an attempt to
      facilitate routine analysis and obtain reproducible conditions or comparable
      results. The influence of sample size, reagent composition and volume, microwave
      power, and duration of heating on the digestion procedure was studied. Pressure
      and temperature inside the reaction vessels were monitored to determine the
      progression of the reaction and to develop optimal conditions. A nine-step
      heating program requiring 36.5 min with microwave power not exceeding 450 W in
      the pulsed mode was found suitable for the digestion of approximately 250 mg fuel
      oil with a mixture of nitric acid (5.0 mL) and hydrogen peroxide (2.0 mL). The
      reproducibility of microwave power was determined in terms of the relative
      standard deviations (n = 3) for temperature (2.7%) and pressure (4.9%) data. The
      vapor pressures obtained with 5.0 mL Milli-Q water (heated) in an 80-mL digestion
      vessel showed good agreement with literature data. The excess acid in the
      resulting digests was removed by evaporation and the concentrations of 24
      elements (Ag, Al, As, Ba, Bi, Ca, Cd, Co, Cr, Cu, Fe, Hg, Mg, Mo, Ni, Pb, Sb, Sn,
      Sr, Ti, Tl, V, U, and Zn) were determined in the diluted digests by inductively
      coupled plasma mass spectrometry (ICP-MS). The experimental results were in good
      agreement with the certified and recommended concentrations for eight elements
      (Al, As, Co, Cr, Ni, Pb, V, Zn) in solutions obtained after one digestion step.
      An additional digestion step, consisting of intermediate cooling and venting
      stages, was required for the accurate determination of Fe. No agreement was
      reached for Ca and Ba even after two-step digestion. The proposed method of
      digestion provided precise results with relative standard deviations generally
      less than 5% for most of the elements determined.

PMID- 11227432
TI  - Ultra trace detection of perfluorocarbon tracers in reservoir gases by
      adsorption/thermal desorption in combination with NICI-GC/MS.
AB  - A new method for the analysis of perfluorocarbon tracers (PFTs) in reservoir
      samples based on adsorption/thermal desorption in combination with NICI-GC/MS is
      presented. The tracer compounds were trapped in tubes filled with a carbon
      molecular sieve and in a two-step procedure thermally desorbed before they were
      analyzed with NICI-GC/MS. The chromatographic background noise, visible on GC/ECD
      systems, due to compounds normally present in petroleum reservoir gases, could
      not be seen with NICI-GC/MS. Determination of the perfluorocarbons in reservoir
      gas samples confirmed the applicability of the method. Tracer concentrations as
      low as 42 femtoliter/liter were detected.

PMID- 11227433
TI  - Speciation of As(III), As(V), MMA and DMA in contaminated soil extracts by HPLC
      ICP/MS.
AB  - A method to separate and quantify two inorganic arsenic species As(III) and As(V)
      and two organic arsenic species, monomethylarsonic acid (MMA) and dimethylarsinic
      acid (DMA), by HPLC-ICP/MS has been developed. The separation of arsenic species
      was achieved on the anionic exchange column IonPac AS11 (Dionex) with NaOH as
      mobile phase. The technique was successfully applied to analyze extracts of two
      contaminated soils, sampled at a former tannery site (soil 1) and a former paint
      production site (soil 2). The soils were extracted at pH values similar to the
      natural environment. Extractions were performed at different pH values with 0.3 M
      ammonium oxalate (pH = 3), milli-Q water (pH = 5.8), 0.3 M sodium carbonate (pH =
      8) and 0.3 M sodium bicarbonate (pH = 11). No organically bound arsenic was found
      in the extracts. As(V) was the major component. Only up to 0.04% of the total
      arsenic contained in soil 1 were mobilized. The highest amount of extracted
      arsenic was found at the highest pH. In the milli-Q water extract of soil 1
      As(III) and As(V) were found. High amounts of As(V) were found in the extracts of
      soil 2. Up to 20% of the total arsenic bound to soil 2 constituents were
      released. The results show that the mobilization of arsenic depended on the pH
      value of the extraction solution and the kind of extracted soil. Dramatic
      consequences have to be expected for pH changes in the environment especially in
      cases where soils contain high amounts of mobile arsenic.

PMID- 11227434
TI  - Use of zwitterionic micelles in the eluent: a new approach for ion
      chromatographic (IC) analysis of ions in biological fluids with direct sample
      injection.
AB  - The problem of column performance degradation due to irreversible binding of
      proteins encountered in ion chromatographic (IC) analysis of ions in protein
      containing samples was overcome by using zwitterionic micelles (e.g., Zwittergent
      3-14) as a portion of the eluent. A zwitterionic micellar eluent showed high
      ability for solubilization of proteins, and, hence, the protein-containing
      samples could be analyzed without need for deproteinization. On the other hand,
      the zwitterionic micelle was insensitive to conductivity but interacted with the
      analyte ions, due mainly to its unique configuration of charges (namely, the
      zwitterionic micelle containing both positively and negatively charged groups but
      carrying no net charge). Using a zwitterionic micellar eluent, the analyte ions
      could be detected selectively and sensitively, and moreover, the selectivity for
      the analyte ions was unique. A conventional anion-exchange column conditioned
      with a Zwittergent-3-14 micellar eluent was applied for the analysis of real
      biological samples (serum and urine) with direct sample injection. The results of
      the successful detection of inorganic anions (Cl-, SO4(2-), NO2-, Br-, and NO3-)
      have demonstrated the usefulness of this new IC approach for the analysis of
      biological samples.

PMID- 11227435
TI  - Separation and detection of selenium-containing proteins in human serum.
AB  - Selenium-containing proteins or their subunits in human serum were separated and
      detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)
      and the amount of selenium in each protein band was determined by HPLC with a
      fluorescence detector after derivatization with 2,4-diaminonaphthalene (DAN).
      This procedure provides a detection limit of 0.06 ng in a linear range of 0-1.5
      ng. A protein is defined as a selenium-containing protein if its mean Se content
      exceeds twice the detection limit (0.12 ng) and twice the standard deviation of
      three replicates in sample determination. At least 4 selenium-containing bands
      with apparent molecular masses of 57-74, 46-56, 40-42 and 21-22 kDa could be
      detected from human serum collected from 4 volunteers.

PMID- 11227436
TI  - Qualitative and quantitative analysis of carbohydrates in green juices (wild mix
      grass and alfalfa) from a green biorefinery by gas chromatography/mass
      spectrometry.
AB  - Green juices from biorefinery original raw material (wild mix grass and alfalfa
      after wet fractionation and protein separation) have been investigated by gas
      chromatography/mass spectrometry. The carbohydrates, involved in the green
      juices, were derivatized and identified by both their retention times in the gas
      chromatogram and EI mass spectra compared to those of pure reference compounds.
      Additionally, chemical ionization mass spectra were recorded for better
      characterizing the carbohydrates present. The carbohydrates which could thus be
      identified, were quantified by response signals with respect to that of the
      internal standard beta-phenyl-D-glucopyranoside.

PMID- 11227437
TI  - Trace analysis of pentachlorophenol (PCP) in wood and wood-based products-
      comparison of sample preparation procedures.
AB  - The main problem with routine analyses of pentachlorophenol (PCP) and sodium
      pentachlorophenolate (Na-PCP) in wood and wood-based products is to determine
      critical PCP-contents. This task requires a reliable analytical method and
      statistical testing. An analytical procedure is described, which permits the
      determination of PCP and Na-PCP with sufficient sensitivity and accuracy. A
      medium size sieve (4 x 4 mm quadratic mesh) was found suitable for the grinding
      step. Different extraction techniques and solvents were tested systematically.
      Extraction by a combination of ultrasonication and shaking in the solvent mixture
      toluene/sulfuric acid showed best recoveries. The eluted PCP and Na-PCP were
      derivatized with acetic anhydride and determined by GC/ECD. The limits of
      detection and determination were 0.14 mg/kg and 0.40 mg/kg, respectively.

PMID- 11227438
TI  - Determination of zinc in pharmaceutical products using an electrodialyser
      incorporated into a flow system.
AB  - An electrodialyser unit has been designed, incorporated into the conduits of a
      flow injection (FI) system, and employed for the removal of interferences in the
      determination of zinc(II) in multivitamin tablets. The proposed system is fully
      computerised and is able to determine zinc(II) at a frequency of 18 samples/h
      with a sample interaction of 0.0015%. The calibration graph is linear between 1
      and 20 mg/L. The detection limit is 0.998 mg/L. The results obtained for zinc(II)
      in multivitamin tablets with the proposed system compared favourably with those
      obtained with the standard manual AAS method.

PMID- 11227439
TI  - Determination of mercury in crude oil by in-situ thermal decomposition using a
      simple lab built system.
AB  - A simple system based on thermal decomposition for the one step determination of
      mercury has been built. This system was applied to the analysis of crude oil and
      related products. Samples were directly introduced into the system without the
      use of chemicals and digestion procedures. After 4 min, matrices and mercury
      compounds were decomposed, and elemental mercury was collected on a gold sand
      trap, and then detected by atomic fluorescence spectroscopy (AFS). In principle,
      any sample can be analyzed by this method provided the sample can be introduced
      into the system quantitatively. The method detection limit was approximately 0.2
      ng/g for 0.04 g of crude oil introduced to the system. Various other samples
      including, biological, environmental, and general merchandise have been analyzed.
      Results obtained have been compared with established traditional methods
      including radiochemical neutron activation analysis (RNAA). Good agreement of
      results between methods was found. Recoveries were close to 100% for certified
      reference materials. Results were independent of mercury species and sample
      types.

PMID- 11227440
TI  - Application of sodium carbonate-zinc oxide decomposition mixture on ICP-AES
      determination of boron in tourmaline.
AB  - Boron in tourmaline, a high refractory mineral with a high boron content
      (approximately 3%), can be determined after aqueous leaching of a sodium
      carbonate-zinc oxide melt. Boron is separated effectively from the major elements
      of matrix, such as silicon, calcium and magnesium and especially from iron, the
      main spectral interfering element. Measurements were performed by inductively
      coupled plasma atomic emission spectrometry. A determination limit of 4 microg/g
      could be achieved when 200 mg of sample are analyzed with a precision of 5.2%
      RSD. This method could be applied to the determination of fluorine in the same
      solution.

PMID- 11227441
TI  - Potentiometric determination of acids and bases using a silica gel based carbon
      epoxy indicator electrode.
AB  - The construction and the application of a silica gel based carbon-epoxy indicator
      electrode for the potentiometric determination of acids and bases are described.
      The effect of composition of silica gel and carbon-epoxy, slope (mV/pH), linear
      response (pH range) and the use for acid-base titrations were investigated. The
      data obtained for the acid-base titrations were compared with those obtained
      using a glass electrode in the same conditions. The electrode showed a linear
      response in the pH 2 to 13 range with a slope of -40.5 +/- 0.4 mV/pH (at 25
      degrees C) and a response time of less than 15 s. The lifetime of the electrode
      was higher than one year (over 6000 determinations) with a decrease of only 5% of
      the initial potentiometric response. The silica gel based carbon-epoxy electrode
      showed excellent results in the end-point indication potentiometric titrations in
      determination of acids and bases. The miniaturization of the proposed electrode
      for flow injection analysis was investigated.

PMID- 11227442
TI  - Extraction of polychlorinated biphenyl with supercritical carbon dioxide, sulfur
      hexafluoride and subcritical water.
AB  - In the extraction of spiked PCB from soil, three extracting fluids were
      investigated: supercritical carbon dioxide (CO2), supercritical sulfur
      hexafluoride (SF6) and subcritical water. Among the tested fluids SF6 appeared to
      be appropriate especially for the extraction of low polar PCB. CO2 and water were
      found to be suitable for the quantitative extraction of all PCB. Water was judged
      as the best because of its low price, good availability and environmental safety.

PMID- 11227443
TI  - Assay of tolnaftate and related impurities by isocratic supercritical fluid
      chromatography.
AB  - Tolnaftate, an antifungal drug (TF) and related impurities arising from
      synthesis, viz., N-methyl-m-toluidine (NMmT) and beta-naphthol-1-chlorothio
      carbamate (beta-NCTC) can be determined by supercritical fluid chromatography.
      Even though it was possible to elute TF completely with neat SCF CO2, the peaks
      of the impurities were found to merge. The chromatographic figures of merit of
      the three analytes such as retention time (tR), capacity factor (k), selectivity
      factor (alpha), no. of theoretical plates (N), were optimized. The three
      compounds can be resolved in 5 min on a Hypersil (250 x 4.0 mm) 5 mu, C18 column
      with supercritical carbon dioxide, modified with 1.96% methanol as the mobile
      phase at 9.81 MPa and at 40 degrees C. Detection was carried out at 220 nm. The
      data as evaluated by the linear regression least squares fit method gave
      linearity ranges from 0.2 to 10.0 microg/mL for TF and NMmT and 0.3 to 10.0
      microg/mL for beta-NCTC with correlation coefficients > 0.99. The method was
      successfully employed to estimate levels of 0.01% for NMmT and 0.02% for beta
      NCTC with respect to TF.

PMID- 11227444
TI  - Preconcentration of pentachlorophenol from sawdust using quinolin-8-ol
      immobilized on controlled-pore glass and determination by liquid chromatography.
AB  - A method for quantitative evaluation of pentachlorophenol (PCP) in sawdust has
      been developed. Pentachlorophenol is extracted from the solid matrix with 0.5 M
      sodium hydroxide and preconcentration was carried out using quinolin-8-ol
      immobilized on controlled pore glass. Determination was carried out by using
      liquid chromatography with detection at 240 nm. Recoveries were between 84 and
      97% at 1-3 microg/g.

PMID- 11227445
TI  - Direct determination of selenoproteins in polyvinylidene difluoride membranes by
      electrothermal atomic absorption spectrometry.
AB  - A method for the direct determination of selenoproteins in plastic membranes
      after protein separation by gel electrophoresis was developed. Quantification was
      based on the determination of the selenium content of the proteins by
      electrothermal atomic absorption spectrometry (ET-AAS) after manual introduction
      of membrane pieces into the graphite furnace. The proteins were separated by
      sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and
      subsequently transferred to a polyvinylidene difluoride (PVDF) membrane by semi
      dry electroblotting. After staining the membrane, the protein bands were excised
      and chemical modifier was added on top of the excised membrane prior to atomic
      absorption measurement. Acceptable linearity was achieved in the range 2-10 ng
      Se, corresponding to selenium concentrations close to 1 mg/L, when aqueous
      solutions of selenomethionine standard as well as selenoprotein standard were
      applied to the membrane. A characteristic mass of 54 +/- 4 pg/0.0044 s was
      obtained for the selenoprotein standard. Protein transfer from polyacrylamide gel
      to the membrane was quantitative and no interferences were introduced. The method
      was used for identification of selenoprotein P after enrichment of the protein
      from human plasma.

PMID- 11227448
TI  - Mathematical algorithm for qualitative and semiquantitative analysis of petroleum
      hydrocarbons in solid wastes using on-line gas chromatography.
AB  - Non-degradated mineral-oils like gasoline, solvent naphtha, diesel fuel, fuel and
      lubricating oils provide a characteristic fingerprint gas chromatogram. This
      visual classification, e.g. in solid wastes, is complicated due to the
      simultaneous presence of several mineral-oils. Therefore, a mathematical
      algorithm for the separation of gas chromatographic fingerprint of "single
      mixtures" of aliphatic hydrocarbons is developed. The technique is essential for
      analysis of time-overlapping "single mixtures" of petroleum hydrocarbons (so
      called "complex mixtures") and it relies on the concentration-varying
      hydrocarbons during evaporation. It is possible to separate the data from the gas
      chromatogram of a "complex mixture" of hydrocarbons into the chromatograms of the
      pure "single mixtures" and to give their respective concentrations. A synthetic
      "complex mixture" of kerosene, diesel fuel and lubricating oil is used to
      illustrate the method.

PMID- 11227446
TI  - An enzyme linked immunoassay for the determination of deoxynivalenol in wheat
      based on chicken egg yolk antibodies.
AB  - An indirect competitive enzyme linked immunoassay (ELISA) for the detection of
      the Fusarium mycotoxin deoxynivalenol (DON) in wheat was developed. Instead of
      the much more common antibody isolation from mammal serum, DON specific
      antibodies were, for the first time, isolated from the eggs of previously
      immunized hens. The limit of detection was 2 microg/L for standard curves and
      spiked wheat extracts. Recoveries for naturally contaminated samples (200-525
      microg/kg) were between 80 and 125% compared with GC-ECD data. Concentrations for
      naturally contaminated samples were chosen with regard to current Austrian
      guidelines concerning DON levels in produce intended for human consumption,
      recommending a maximum of 500 microg DON/kg.

PMID- 11227449
TI  - New low-index liquid refractive index standard: SRM 1922.
AB  - A new standard for the calibration of refractometers has been developed. Standard
      Reference Material (SRM) 1922 is a mineral oil with a refractive index nD =
      1.46945 at 20 degrees C, which is within the range of the Brix scale (% sucrose).
      The change in refractive index with temperature (dn/dT) has been characterized
      for the range 15 degrees C to 35 degrees C to allow for calibrations within that
      range of temperatures. The refractive indices were measured at 5 wavelengths in
      the visible spectrum by using the method of minimum deviation with a +/- 2-3 x
      10(-5) uncertainty at 20 degrees C. The values of nD and dnD/dT were determined
      by fits of a two-term Cauchy function to the values at the measured wavelengths
      with a +/- 6 x 10(-5) uncertainty in nD at 20 degrees C.

PMID- 11227450
TI  - River sediment (S-37)--a new analytical quality control material ensuring
      comparability of chlorinated hydrocarbon analysis during an international
      environmental study in China.
AB  - A sediment reference material (S-37) was prepared as analytical quality control
      material to be used within an international project on polychlorinated
      hydrocarbon analysis in two Chinese rivers. The raw material was sampled during a
      cruise on Yangtse River and transported afterwards to the JRC Ispra for further
      processing. The material was treated according to the general principles
      applicable for candidate reference material production. After a thorough
      homogeneity study of the bulk the material was bottled. A total of 1,080 bottles
      each containing 50 g of dry sediment powder was obtained. Final homogeneity and
      stability testing proved the material to be fit for the purpose. Isotope dilution
      GC/MS was used to establish target values for pentachlorobenzene (1.17 +/- 0.08
      ng/g), hexachlorobenzene (3.60 +/- 0.17 ng/g), octachlorostyrene (0.19 +/- 0.01
      ng/g), pentachloroanisole (0.52 +/- 0.02 ng/g), alpha-HCH (0.70 +/- 0.05 ng/g),
      beta-HCH (1.38 +/- 0.18 ng/g), gamma-HCH (0.83 +/- 038 ng/g), 2,4'-DDT (0.36 +/-
      0.04 ng/g), 2,4'-DDE (0.29 +/- 0.02 ng/g), 2,4'-DDD (0.49 +/- 0.02), 4,4'-DDT
      (3.42 +/- 0.47 ng/g), 4,4'-DDD (1.29 +/- 0.17 ng/g), PCB 28 (0.11 +/- 0.01 ng/g),
      PCB 52 (0.09 +/- 0.003 ng/g), PCB 101 (0.07 +/- 0.003 ng/g), PCB 138 (0.06 +/-
      0.003 ng/g) and PCB 153 (0.06 +/- 0.003 ng/g). Furthermore, indicative values for
      major and minor constituents as well as for polychlorinated dibenzodioxines and 
      furanes were measured.

PMID- 11227451
TI  - Amperometric detection studies of Nafion/indium hexacyanoferrate film for the
      determination of electroinactive cations in ion chromatography.
AB  - An amperometric detector based on the chemical modification of Nafion and indium
      (III) hexacyanoferrate (II, III) thin film (Nafion/In-CN-Fe) onto a glassy carbon
      (GC) electrode, was first successfully used for the determination of
      electroinactive cations (Li+, Na+, K+, Rb+, Cs+, NH4+) in single column ion
      chromatography (IC). A set of well-defined peaks of electroinactive cations was
      obtained. The detection limits of the cations are 8.9 x 10(-6) mol/L for Li+, 2.3
      x 10(-6) mol/L for Na+, 5.2 x 10(-6) mol/L for K+, 4.8 x 10(-6) mol/L for Rb+,
      4.0 x 10(-6) mol/L for Cs+ and 5.3 x 10(-6) mol/L for NH4+ at a single-to-noise
      ratio of 3. The proposed method was quick, sensitive and simple. The cations in
      rainwater and mineral water were successfully analyzed by this method.

PMID- 11227452
TI  - Preconcentration of trace amounts of silver ion in aqueous samples on octadecyl
      silica membrane disks modified with hexathia-18-crown-6 and its determination by
      atomic absorption spectrometry.
AB  - A simple and reliable method has been developed to selectively separate and
      concentrate trace amounts of silver ion from aqueous samples for the subsequent
      measurement by atomic absorption spectrometry. Ag+ ions are absorbed
      quantitatively during passage of aqueous samples through an octadecyl-bonded
      silica membrane disk modified by hexathia-18-crown-6. Almost all matrix elements
      will pass through the disk to drain. The retained Ag+ ions are then stripped from
      the disk with a minimal amount of thiosulfate solution as eluent. The proposed
      method permitted large enrichment factors of about 200 and higher. The limit of
      detection of the proposed method is 50 ng Ag+ per 1,000 mL. The effects of
      various cationic interferences on the recovery of silver in binary mixtures were
      studied. The method was applied to the recovery of Ag+ ions from different
      synthetic and water samples.

PMID- 11227456
TI  - Precise and sensitive determination of nitrite by coulometric backtitration under
      flow conditions.
AB  - A novel method performing for coulometric backtitrations in flow channels was
      developed, which was applied for the precise and sensitive determination of low
      concentrations of nitrite. Under acid conditions nitrite is reacting
      stoichiometrically with hydrazine, the remained excess of which is backtitrated
      with electrogenerated bromine. The titration course is recorded either
      amperometrically or chemiluminometrically. Hydrazine can be determined precisely
      and accurately in the range between 0.1 microM and 1 mM without calibration.
      Nitrite is reduced by hydrazine according to the reaction 2 NO2- + 2 H+ + NH2-NH2
      --> N2O + N2 + 3 H2O. Applying the amperometric and the chemiluminometric end
      point location nitrite was determined accurately and precisely in the ranges 0.25
      65 microM and 0.10-50 microM, respectively. The method was applied to the
      determination of nitrite in tap and river water.

PMID- 11227457
TI  - Flow injection spectrophotometric determination of anionic surfactants using
      methyl orange as chromogenic reagent.
AB  - A flow injection(FI) spectrophotometric method for the determination of anionic
      surfactants was developed on the basis of the competition for the cationic
      surfactant cetyl pyridine (CP+) chloride between the acidic dye methyl orange
      (MO) and anionic surfactants. In a pH 5.0 medium the cation of cetyl pyridine
      (CP+) reacts with dissociated methyl orange (MO-) to form an ion-associate
      complex, causing a blue shift of lambda(max) from 465 nm for MO- to 358 nm for
      the CP+ x MO- associate. The MO- in the ion-associate complex can be
      quantitatively substituted by such anionic surfactants as sodium dodecyl benzene
      sulfonate (DBS) or sodium lauryl sulfate (LS), leading to an increase in the
      absorbance measured at 465 nm. This increased absorbance value is proportional to
      the concentration of anionic surfactants. Various chemical and physical
      parameters for the FI spectrophotometric method were optimized, and interference
      free levels were examined. At the optimized conditions, Beer's law was obeyed in
      the range 1.4 approximately 25 mg/L sodium DBS for an injected sample volume of
      180 microL, and a detection limit of 0.22 mg/L for sodium DBS was achieved at a
      sampling rate of 90 h(-1). Eleven determinations of a 16 mg/L sodium DBS solution
      gave a RSD of 0.4%. The proposed method has successfully been applied to the
      determination of anionic surfactant concentration in waste water and in
      detergents.

PMID- 11227458
TI  - Estimation of unsaturated hydrocarbon pollutants in air based on selective gas
      chromatography with ozone.
AB  - Regular monitoring of toxic organic pollutants in air is a very important issue
      in environmental pollution control. Among these, unsaturated hydrocarbon
      pollutants (UHP) such as ethylene and beta-propylene and another 18 olefins are
      of prime importance. A very fast method for the individual identification of UHPs
      in air is proposed. This method is based on gas-chromatographic separation with
      selective detection of unsaturated organic compounds (UOC) and on the chemical
      reaction of UOC with ozone in the gas phase. In view of the mathematical model
      derived for this ozonation process, a comparison of FID-chromatogram and
      ozonogram can be carried out for identification of the contaminants. This
      identification can be performed without preliminary separation in the presence of
      the main components. The method provides a high sensitivity (< 0.005 to 0.72 mass
      %) and selectivity.

PMID- 11227459
TI  - A simplified HPTLC screening method for the estimation of the PAH content in soil
      samples.
AB  - Based on a highly significant correlation between the visual fluorescing fraction
      of PAH on the one hand and the total EPA-PAH16 content in mineral soils on the
      other hand, a deliberately incomplete RP-TLC separation of these compounds into a
      few fingerprint-like compressed bands within a determined "PAH window" has been
      achieved. The resulting band-pattern does not interfere normally with the more or
      less non-polar phenolic compounds which are associated with natural soil humic
      substances. The extraction step has been extremely simplified with regard to the
      quantity of the soil sample and of the extractant. The accuracy of this procedure
      has been ascertained by means of recovery experiments with an artificial soil
      enriched with PAH. A single spot application mode and an evaluation scheme allow
      the estimation of EPA-PAH16 contents of soil samples in relation to threshold
      values (1 or 5 or 10 mg/kg). This HPTLC screening method has been compared
      against standard HPLC methods. The simplified extraction step and the separation
      by HPTLC minimizes the actual costs and the time spent per sample.

PMID- 11227461
TI  - Microwave-assisted extraction method for the determination of atrazine and four
      organophosphorus pesticides in oranges by gas chromatography (GC).
AB  - A simple and rapid microwave assisted extraction (MAE) method is presented for
      the determination of atrazine and four organophosphorus pesticides
      (parathionmethyl, chlorpyriphos, fenamiphos and methidathion) in orange peel. The
      experimental variables that affect the MAE method, such as temperature, sample
      quantity, extraction time, nature and volume of organic solvents, were optimized.
      The MAE method was optimized using an experimental design. The results suggest
      that temperature and sample quantity are statistically significant factors. It
      was concluded that the five pesticides could be efficiently extracted from 1.5
      2.5 g of orange peel with 10 mL of hexane/acetone (1: 1) mixture at 90 degrees C
      in 9 min with microwave power set at 50% (475 W). After optimization these
      factors, recoveries ranged from 93 to 101% with a relative standard deviation
      ranging from 1 to 3%. The extracts were analyzed by gas chromatography with a
      nitrogen-phosphorus detector (GC-NPD).

PMID- 11227460
TI  - Determination of Cu, Pb, Cd, and Zn in river sediment extracts by sequential
      injection anodic stripping voltammetry with thin mercury film electrode.
AB  - Determination of Cu, Pb, Cd and Zn was performed in sediment extracts obtained
      according to the three steps sequential extraction procedure proposed by the
      European Community Standards, Measurements and Testing Program. The metal content
      was determined by anodic stripping voltammetry with a thin mercury film electrode
      controlled by a sequential injection (SIA) system. The proposed method improved
      the reproducibility of conventional anodic stripping voltammetry, as well as the
      sample throughput, allowing analysis of 30 to 45 samples per hour. The influence
      of flow rate and sample volume was studied to achieve an adequate sensitivity for
      the leachate studied. No interferences due to adsorption of organic matter,
      colloids, or complexes with slow rate of dissociation were observed. The
      intermetallic formation of Cu-Zn was avoided by forming the mercury film in
      presence of Ga(III) ions in the SIA system, resulting in low consumption of
      reagent in comparison to flow injection or continuous flow systems. Results were
      in good agreement with those obtained by Induced Coupled Plasma - Atomic Emission
      Spectroscopy (ICP-AES).

PMID- 11227462
TI  - Electrothermal vaporization system using furnace-fusion technique for the
      determination of lead in botanical samples by inductively coupled plasma atomic
      emission spectrometry.
AB  - A new approach to sample digestion, subsequent vaporization and introduction into
      an inductively coupled plasma atomic emission spectrometer was developed for the
      direct determination of lead. To each small sample cuvette made of tungsten, a
      mixture of a ground solid sample and powdered diammonium hydrogenphosphate was
      precisely weighed. The cuvette was positioned onto the tungsten boat furnace
      (TBF) incorporating a vaporizer. Tetramethylammonium hydroxide solution was
      added. Then the cuvette was heated and maintained at a wet-digestion temperature
      to decompose the solid sample. After digestion, the temperature was elevated to
      generate the analyte vapor for introduction into a plasma. Since the solid
      samples were wet-digested in the sample cuvettes before vaporization, they could
      be analyzed by using a calibration curve prepared from aqueous standard
      solutions. This method was applied to the determination of lead in several
      biological materials with satisfactory results.

PMID- 11227463
TI  - Direct determination of lead in biological samples by electrothermal vaporization
      inductively coupled plasma mass spectrometry (ETV-ICP-MS) after furnace-fusion in
      the sample cuvette-tungsten boat furnace.
AB  - The newly conceived electrothermal vaporization (ETV) system using a tungsten
      boat furnace (TBF) sample cuvette was designed for the direct analysis of solid
      samples with detection by inductively coupled plasma mass spectrometry (ICP-MS).
      Into this small sample cuvette, a solid mixture of the biological samples and
      diammonium hydrogenphosphate powder as a fusion flux was placed and situated on a
      TBF. Tetramethylammonium hydroxide solution was added to the mixture. After the
      on-furnace digestion had been completed, the analyte in the cuvette was vaporized
      and introduced into the ICP mass spectrometer. The solid samples were analyzed by
      using a calibration curve prepared from the aqueous standard solutions. The
      detection limit was estimated to be 5.1 pg of lead, which corresponds to 10.2 ng
      g(-1) of lead in solid samples when a prepared sample amount of 1.0 mg was
      applied. The relative standard deviation for 8 replicate measurements obtained
      with 100 pg of lead was calculated to be 6.5%. The analytical results for various
      biological samples are described.

PMID- 11227465
TI  - Determination of non-ortho polychlorinated biphenyls in environmental Standard
      Reference Materials.
AB  - The concentrations of three non-ortho ("coplanar") polychlorinated biphenyls,
      3,3',4,4'-tetrachlorobiphenyl (IUPAC PCB 77), 3,3',4,4',5-pentachlorobiphenyl
      (IUPAC PCB 126), and 3,3',4,4',5,5'-hexachlorobiphenyl (IUPAC PCB 169), were
      determined in five NIST Standard Reference Materials (SRMs) of environmental and
      biological interest. The measured levels were approximately between (0.2 to 1.3)
      ng/g in SRM 1588a (Organics in Cod Liver Oil), (0.3 to 9) ng/g in SRM 1944 (New
      York/New Jersey Waterway Sediment), (0.2 to 0.4) ng/g in SRM 1945 (Organics in
      Whale Blubber), (1 to 18) ng/g in SRM 2974 (Organics in Freeze-dried Mussel
      Tissue [Mytilus edulis]), and (0.1 to 0.4) ng/g in candidate SRM 1946 (Lake
      Superior Fish Tissue). PCB 169 was present at < 0.1 ng/g in SRMs 1944 and 2974.

PMID- 11227466
TI  - Multielemental analysis in small amounts of environmental reference materials
      with inductively coupled plasma mass spectrometry.
AB  - The lowest possible sample weight for performing multielemental trace element
      analysis on environmental and biological samples by ICP-MS has been investigated.
      The certified reference materials Bovine Liver NIST SRM 1577b, Human Hair NCS DC
      73347 and Oriental Tobacco Leaves CTA-OTL-1 were applied at sample weights (1, 5,
      20 and 50 mg aliquots, n = 10) which were significantly lower than those
      recommended with most recoveries in the range of 95-110%. Samples were digested
      in a mixture of nitric acid, hydrogen peroxide and hydrogen fluoride by closed
      vessel microwave digestion. Multielemental analysis was performed with an
      optimized ICP-QMS method. Aqueous standard solutions were applied for external
      calibration with rhodium as the internal standard element. The detection limits
      varied between 0.02-0.38 microg/g for Li, Na, Cr, Mn, Ni, Cu, Zn, Sr, Cd, Ba and
      Pb, and up to 1.92 microg/g for Mg, Al, Ca, Fe and Ni. Digested human plasma
      samples were spiked with multielemental solution (0.5-10 microg/L) to test the
      analytical method and the recoveries were 95-105% for most analytes. Our results
      show that in the case of homogeneous SRMs it is possible to use them in very low
      amounts (1-5 mg) for method development and quality control.

PMID- 11227469
TI  - Dot-immunobinding assay using indirect photoacoustic measurement.
AB  - Dot-immunobinding assay of hepatitis B surface antigen (HBsAg) was performed by a
      conventionally dot-ELISA technique with 4-chloro-1-naphthol staining, and the
      quantitative results were measured by an indirect photoacoustic method. In this
      method, a 2-mW helium-neon laser was applied to provide the excitation beam, the
      blue spots on the membrane were detected in a piezoelectric transducer-based
      photoacoustic cell. The operational conditions of measurement were optimized. A
      significant difference from the negative human serum was obtained for 50 pg in
      HBsAg detection. The method proposed provides a sensitive quantitative technique
      for dot-immunobinding assay.

PMID- 11227470
TI  - Hydrophilic sensor membrane based on cation-selective protic chromoionophore.
AB  - The first potassium optode based on a protic chromoionophore immobilized in a
      hydrogel matrix is presented. The highly selective protic chromoionophore
      consists of a cryptohemispherand moiety and a trinitroanilino chromophore part.
      The acidifying power of potassium ions over sodium ions is 0.6 pH units. This
      correlates with the findings in solution. In contrast to several crown and aza
      crown based chromophores the highly pre-organized moiety allows ion detection
      even in aqueous environment. The detection limit for potassium ions at pH 7.7 is
      5 microM.

PMID- 11227474
TI  - Automated multiple solid phase micro extraction. An approach to enhance the limit
      of detection for the determination of pesticides in water.
AB  - A method was developed to decrease the limit of detection (LOD) for pesticide
      residue analysis in water using multiple SPME. To enhance the absolute amount
      transferred to the GC column an enrichment step is integrated in the SPME/GC
      analysis. A series of several extraction and desorption steps are performed and
      the analytes are trapped at the front of the cold GC column before the GC
      analysis is started. The parameters mainly influencing this enrichment are the
      equilibrium time, the slope of the adsorption time/peak area profile at its
      start, the number and the duration of the extraction steps. The role of these
      parameters was investigated.

PMID- 11227475
TI  - Determination of palladium in airborne particulate matter in a German city.
AB  - The part of palladium in ambient urban air that is bound to particles and soluble
      in aqua regia was determined by means of sorbent extraction, coupled with
      graphite furnace atomic absorption spectrometry (GFAAS) and laser absorption
      fluorescence spectrometry (LAFS). Samples of about 200 m3 air were taken in a
      suburb of Berlin, Germany. The coupling of the selective and automated pre
      concentration procedure for Pd as N,N-diethyl-N'-benzoylthiourea complex with the
      respective detection methods proved to be sufficiently sensitive. Severe
      interference with other matrix constituents, occurring mainly by direct LAFS
      detection, could be overcome and the detection limit was improved tremendously.
      The concentration of Pd in ambient air was determined to be in the range from 0.2
      to 14.6 pg/m3.

PMID- 11227476
TI  - Oil-in-water emulsions as suitable working media for the direct polarographic
      determination of aziprotryne and desmetryne from its organic extracts in water
      samples.
AB  - The electroanalytical behavior of the reduction of the herbicides aziprotryne (2
      azido-4-isopropylamino-6-methylthio-1,3,5-triazine) and desmetryne (4
      isopropylamino-6-methylamino-2-methylthio-1,3,5-triazine) in oil-in-water
      emulsions is reported. This medium allows the differential pulse polarographic
      determination of these s-triazines directly from their sample extracts in an
      appropriate organic solvent. Sodium pentanesulfonate was chosen as the most
      suitable surfactant to be used as emulsifying agent, whereas ethyl acetate was
      selected as the organic solvent to form the emulsions. The peak current was
      maximum in a 0.3 mol L(-1) HClO4 medium of the continuous aqueous phase for
      aziprotryne, and at pH 3.0 for desmetryne, and the potential became more negative
      as the pH increased for both herbicides. The limiting current is diffusion
      controlled and the electrode process is irreversible. Four electrons are involved
      in the overall electrochemical reduction process as determined by controlled
      potential coulometry, whereas the alpha n(a) values suggested that two electrons
      are involved in the rate-determining step. Using differential pulse polarography,
      aziprotryne and desmetryne can be determined in the emulsified medium over the
      concentration ranges 1.0 x 10(-7)-1.0 x 10(-4) mol L(-1), with limits of
      detection of 4.5 x 10(-8) mol L(-1) and 6.6 x 10(-8) mol L(-1), respectively. The
      method was applied to the determination of aziprotryne and desmetryne in spiked
      irrigation water. At concentration levels of 6.0 x 10(-7) mol L(-1) aziprotryne
      and 4.0 x 10(-7) mol L(-1) desmetryne, recoveries of 94 +/- 3% and 94 +/- 4%,
      respectively, were obtained after preconcentration on Sep-Pack C18 cartridges.
      Finally, partial least-squares regression (PLSR) has been used for treatment of
      the polarographic data obtained from mixtures of aziprotryne, desmetryne and
      simazine in oil-in-water emulsions. The size of the calibration set was of 29
      samples by ninety two current measurements at different potentials. Prediction of
      the herbicides concentration within the range 1.0 x 10(-6)-1.0 x 10(-5) mol L(-1)
      was possible.

PMID- 11227477
TI  - Determination of s-triazines with copper and glassy carbon electrodes. Flow
      injection analysis of aziprotryne in water samples.
AB  - The detection and determination of s-triazines, atrazine-desethyl and aziprotryne
      by cyclic voltammetry and an amperometric method using a metallic copper
      electrode and a glassy carbon electrode are described. The concentrations of
      atrazine-desethyl and aziprotryne in 0.1 M NaOH solutions were determined using
      the oxidation signal corresponding to the Cu(0)/Cu(I) redox process. The
      detection level calculated for these s-triazines were 0.3 and 0.5 microg/mL of
      analyte, respectively. The glassy carbon electrode was shown to give sensitive
      reduction response to aziprotryne in flow injection mode. No special activation
      was required for the glassy carbon electrode. A detection limit of 0.2 microg/mL
      (20 ng aziprotryne) was obtained for a sample loop of 0.1 mL at a fixed potential
      of -1.0 V (vs. Ag/AgCl) in 0.1 M HCl and a flow rate of 3.5 mL/min. Furthermore,
      the glassy carbon electrode showed stable response in such a system, and the
      relative standard deviation was only 2.7% using the same surface, and 6.3% using
      different surfaces. The method developed was applied to the determination of
      aziprotryne in environmental and tap water samples; using a prior solid-phase
      extraction step, aziprotryne concentrations lower than 1.0 ng/mL could be
      measured.

PMID- 11227478
TI  - Efficiency of solvent extraction methods for the determination of methyl mercury
      in forest soils.
AB  - Methyl mercury was determined by gas chromatography, microwave induced plasma,
      atomic emission spectrometry (GC-MIP-AES) using two different methods. One was
      based on extraction of mercury species into toluene, pre-concentration by
      evaporation and butylation of methyl mercury with a Grignard reagent followed by
      determination. With the other, methyl mercury was extracted into dichloromethane
      and back extracted into water followed by in situ ethylation, collection of
      ethylated mercury species on Tenax and determination. The accuracy of the entire
      procedure based on butylation was validated for the individual steps involved in
      the method. Methyl mercury added to various types of soil samples showed an
      overall average recovery of 87.5%. Reduced recovery was only caused by losses of
      methyl mercury during extraction into toluene and during pre-concentration by
      evaporation. The extraction of methyl mercury added to the soil was therefore
      quantitative. Since it is not possible to directly determine the extraction
      efficiency of incipient methyl mercury, the extraction efficiency of total
      mercury with an acidified solution containing CuSO4 and KBr was compared with
      high-pressure microwave acid digestion. The solvent extraction efficiency was
      93%. For the IAEA 356 sediment certified reference material, mercury was less
      efficiently extracted and determined methyl mercury concentrations were below the
      certified value. Incomplete extraction could be explained by the presence of a
      large part of inorganic sulfides, as determined by x-ray absorption near-edge
      structure spectroscopy (XANES). Analyses of sediment reference material CRM 580
      gave results in agreement with the certified value. The butylation method gave a
      detection limit for methyl mercury of 0.1 ng g(-1), calculated as three times the
      standard deviation for repeated analysis of soil samples. Lower values were
      obtained with the ethylation method. The precision, expressed as RSD for
      concentrations 20 times above the detection limit, was typically 5%.

PMID- 11227479
TI  - Determination of carbendazim in soil samples by anodic stripping voltammetry
      using a carbon fiber ultramicroelectrode.
AB  - A method for the determination of carbendazim (MBC) by anodic stripping
      voltammetry using a carbon fiber ultramicroelectrode was developed. The
      ultramicroelectrode was made in our laboratory and its electrochemical behavior
      was characterized by measuring the electrochemical response with a solution of
      potassium ferricyanide. The optimum parameters used for the determination of MBC
      are the following: 0.05 M phosphate buffer at pH 2.0 as supporting electrolyte; a
      scan rate of v = 10.00 V s(-1) and an accumulation potential of Eac = 0.00 V. The
      MBC was determined in a soil sample with the method proposed and the results
      found were comparable to those obtained by HPLC.

PMID- 11227480
TI  - Determination of Ca, Mg, Fe, Cu, and Zn in blood fractions and whole blood of
      humans by ICP-OES.
AB  - Inductively coupled plasma-optical emission spectrometry (ICP-OES) was applied to
      the determination of the elements Ca, Mg, Fe, Cu, and Zn in blood plasma,
      erythrocytes, lymphocytes, and whole blood to obtain reliable data on their
      distribution in blood fractions. The samples were carefully collected to avoid
      contamination. Two different nebulizers (Babington and Meinhard) were tested and
      optimized for this analytical problem. Line selections for all elements of
      interest were performed (LODs were 0.8 microg/L for Ca, 1.7 microg/L for Cu, 3.0
      microg/L for Fe, 1.1 microg/L for Mg, and 4.2 microg/L for Zn). Recoveries were
      determined as approx. 100%, and standard reference material was analyzed to
      obtain reliable data on element distribution. The optimized method was applied to
      the determination of Ca, Mg, Fe, Cu, and Zn in the course of a clinical study on
      blood and blood fractions of two groups of humans of differing health. The
      concentrations measured in blood fractions were verified by balancing with the
      values found in whole blood.

PMID- 11227481
TI  - Application of ACC method to synchronous luminiscence: determination of alpha
      tocopherol and alpha-tocopheryl acetate in beverages.
AB  - A new method based on the Q parameter, that permits the determination of the
      C(compound A)/C(compound B) ratio without preparing calibration graphs of the two
      compounds, is proposed. This method has been applied to signals obtained by
      synchronous luminiscence. Simultaneous determination of alpha-tocopherol and
      alpha-tocopheryl acetate in beverages using synchronous fluorescence has been
      carried out. To isolate the compounds from samples, liquid extraction with n
      hexane as the organic phase was employed. The presence of interferences was
      tested using the apparent content curves (ACC) method and the C(alpha
      tocopherol)/C(alpha-tocopheryl acetate) ratio was calculated using the Q
      parameter. The reproducibility and detection limit for the determination of alpha
      tocopherol and alpha-tocopheryl acetate were 6.6% and 0.016 mg/L and 1.8% and
      0.017 mg/L, respectively.

PMID- 11227482
TI  - Determination of marker constituents in radix Glycyrrhizae and radix Notoginseng
      by near infrared spectroscopy.
AB  - High-performance liquid chromatographic (HPLC) methods were developed for the
      determination of glycyrrhizin in radix Glycyrrhizae and ginsenosides Rb1, Rb2,
      Rc, Rd, Re, Rf and Rg, in radix Notoginseng. These methods were used as reference
      methods for near-infrared (NIR) spectroscopy. Spectroscopic calibrations were
      developed for the determination of glycyrrhizin, the total content of
      ginsenosides and the individual major ginsenosides Rb1, Rd, Re and Rg1. Standard
      errors of cross validation (SECV) were 1.22 mg g(-1) for glycyrrhizin
      (concentration range 21.3-34.1 mg g(-1)) and 0.99 mg g(-1) for the sum of
      ginsenosides (concentration range 55.3-71.1 mg g(-1)). The corresponding
      coefficients of determination (R2) were 0.94 and 0.98, respectively. The SECVs
      were generally less than a factor of 2.5 of the repeatability standard deviation
      of the HPLC methods.

PMID- 11227484
TI  - Fluorimetric determination of methylmercury as an ion-association complex with
      rhodamine B in the presence of iodide.
AB  - A fluorimetric method for the determination of methylmercury was established. The
      method was based on the formation of an ionic pair between iodide-methylmercury
      rhodamine B in hydrochloric acid, which can be extracted with benzene. The
      fluorescence emission was measured at lambda(ex)/lambda(em) 575/590 nm, and the
      experimental variables and possible interference were studied. The linear
      calibration range was 4 x 10(-8) mol/L to approximately 5 x 10(-7) mol/L with a
      correlation coefficient of 0.9992. The detection limit was 1 x 10(-8) mol/L. The
      method was used to determine methylmercury in human hair. The recovery was in the
      range of 91% to 105% and the relative standard deviation was 2.8%. The results
      agreed with those obtained by gas chromatography with electron capture detection.

PMID- 11227486
TI  - Caspase-dependent and -independent death pathways in cancer therapy.
AB  - The majority of current anticancer therapies induce tumor cell death through the
      induction of apoptosis. Alterations in the apoptotic pathways may determine tumor
      resistance to these therapies. Activation of the proteolytic cascade involving
      caspase family members is a critical component of the execution of cell death in
      apoptotic cells. However, recent studies suggest that cell death can proceed in
      the absence of caspases. In this review we describe the role of caspase-dependent
      and -independent pathways as targets for anticancer treatment. A better
      understanding of diverse modes of tumor cell death will help to avoid ineffective
      treatment and provide a molecular basis for the new strategies targeting caspase
      independent death pathways in apoptosis-resistant forms of cancer.

PMID- 11227488
TI  - zVAD-fmk and DEVD-cho induced late mitosis arrest and apoptotic expressions.
AB  - Cell growth in human Chang liver cells was arrested in late mitosis with 600
      microM zVAD-fmk. Associated cell death manifested cell shrinkage and phagocytic
      marking shown by phosphatidylserine (PS) externalization, in a dose-dependent
      manner. While low molecular weight internucleosomal ladder cleavages were
      suppressed, there were however high molecular weight DNA cleavages extending up
      to megabase level in association with chromatin condensation that appeared more
      marked than the staurosporine-induced positive-apoptosis control. Caspase-3
      activity was suppressed. Specific caspase-3 inhibitor DEVD-cho also produced cell
      growth suppression with late mitosis arrest, and cell shrinkage which was
      expressed concomitantly with phagocytic PS marking in similar dose-dependent
      manners at 50 to 100 microM concentrations. Cell shrinkage, PS externalization,
      and high molecular weight DNA cleavages associated with chromatin condensation
      without 200 bp ladder fragmentations, were dissociated from caspase-3 activity.
      Anti-caspases inducing late mitosis arrest provided fresh insights into late
      mitosis progression.

PMID- 11227487
TI  - Urinary proteins with pro-apoptotic and antitumor activity.
AB  - Analysis of the protein composition of urine has been the subject of much
      research that has captured the interest of scientific groups over the years. A
      number of factors have been isolated from urine that possess anti-neoplastic
      activities as seen both in vitro and in vivo studies. The urine from pregnant
      women and commercial preparations of crude clinical grade human chorionic
      gonadotropin contain factors (HAF for hCG associated factor) with anti-Kaposi's
      sarcoma activity. Also found in urine with activity are eosinophil-derived
      neurotoxin (EDN), anti-neoplastic urinary protein (ANUP), inhibin, activin A, and
      angiostatin. The anti-cancer activity of urinary proteins is associated with
      apoptosis of endothelial cells and of tumor-associated endothelial cells. A
      better understanding of the biological functions of these various urinary
      proteins, and of others that remain to be discovered, should provide insights
      into novel cell regulatory systems operating during pregnancy.

PMID- 11227489
TI  - A short peptide derived from the antisense homology box of Fas ligand induces
      apoptosis in anti-Fas antibody-insensitive human ovarian cancer cells.
AB  - We found that a short synthetic peptide corresponding to the "antisense homology
      box" of Fas ligand induced apoptotic cell death of Fas-expressing human ovarian
      cancer cell lines. The peptide was deduced from residues 256-265 of human Fas
      ligand, based on the hypothesis that it should contain a specific binding site to
      the corresponding Fas. Interestingly, the ovarian cancer cell line NOS4, which
      was sensitive to anti-Fas antibody induced apoptosis, was not affected by the
      peptide, whereas another cell line, SKOV-3, which was insensitive to anti-Fas
      antibody, was killed by the peptide. Thus, this short peptide was shown to have a
      unique activity to induce apoptosis in human ovarian cancer cells in a manner
      different from anti-Fas antibody.

PMID- 11227490
TI  - Bcl-2 protects against apoptosis-related microtubule alterations in neuronal
      cells.
AB  - Bcl-2 is a gene with clear anti-apoptotic properties in neurodegenerative
      conditions. One of the earliest hallmarks of degeneration in neuronal cell
      cultures is the loss of neurite morphology. Therefore the effect of Bcl-2 on
      neuronal morphology and microtubule stability was studied in nerve growth factor
      differentiated PC12 cells. Microtubule dynamics were modulated using the
      microtubule stabilizer taxol and the microtubule destabilizer, okadaic acid, a
      protein phosphatase inhibitor. It was shown that Bcl-2 protects against both
      taxol- and okadaic acid induced neurite retraction. Bcl-2 overexpression also
      significantly reduced the increased ratio of acetylated tubulin over total
      tubulin induced by taxol treatment. Interestingly, Bcl-2 attenuates the decrease
      of the same ratio after exposure to okadaic acid, suggesting that Bcl-2 is able
      to normalize the level of acetylated tubulin. In addition, cell death and nuclear
      fragmentation, induced by okadaic acid, were reduced in Bcl-2 overexpressing
      cells. This protection is either downstream or independent of tau phosphorylation
      as quantitative immunocytochemistry with AT8 showed that Bcl-2 did not modify the
      level of tau phosphorylation. The data suggest that the protective effect of Bcl
      2 on the neuronal cytoskeleton is probably linked to changes in the post
      translational modification of tubulin.

PMID- 11227491
TI  - Apoptosis in fatal Ebola infection. Does the virus toll the bell for immune
      system?
AB  - In fatal Ebola virus hemorrhagic fever massive intravascular apoptosis develops
      rapidly following infection and progressing relentlessly until death. While data
      suggest that T lymphocytes are mainly deleted by apoptosis in PBMC of human fatal
      cases, experimental Ebola infection in animal models have shown some evidence of
      destruction of lymphocytes in spleen and lymph nodes probably involving both T
      and B cells. Nevertheless, we are able to conclude from the accumulated evidence
      that early interactions between Ebola virus and the immune system, probably via
      macrophages, main targets for viral replication, lead to massive destruction of
      immune cells in fatal cases.

PMID- 11227492
TI  - Cloning and characterization of an apoptosis-associated gene in the human
      placenta.
AB  - Placenta is a transient feto-maternal association that develops during mammalian
      pregnancies. Human placental tissue during the first trimester of pregnancy is an
      actively dividing and differentiating tissue, while near term, it represents a
      fully differentiated unit performing many life-sustaining functions for the
      fetus. Previous studies have demonstrated that the percentage of placental cells
      that undergo apoptosis is greater at full term as compared to the first trimester
      of pregnancy. In this study, we undertook a study aimed at gaining an insight
      into the kind of genes expressed in the two developmentally distinct stages of
      gestation ie, the first trimester and term using Differential Display RT-PCR.
      Cloning and sequencing of one of the differentially expressed cDNAs from term
      placental tissue revealed that it is a novel gene, referred to as T-18 in the
      text. In this study, we also examined the regulation of this gene during
      apoptosis in the human placenta. A model for analysis of placental apoptosis was
      established by incubating placental villi in serum-free culture medium. It was
      observed that apoptosis occurred rapidly following incubation of placental villi
      without tropic support, and the proposed free-radical scavenger, superoxide
      dismutase (SOD) suppressed apoptosis in the placenta. Interestingly, the levels
      of T-18 mRNA increased significantly during spontaneous induction of apoptosis
      and decreased when apoptosis was blocked by SOD. These data clearly suggest that
      there is a strong correlation between the expression of T-18 and placental
      apoptosis and that T-18, may play a significant role in this process.
      Furthermore, the establishment of a defined in vitro explant culture model should
      facilitate elucidation of factors, which regulate apoptosis in human placenta.

PMID- 11227493
TI  - Caspase-3-dependent and caspase-3-independent pathways leading to chromatin DNA
      fragmentation in HL-60 cells.
AB  - Apoptosis induced by etoposide (VP-16) in HL-60 cells was confirmed to be caspase
      dependent. It was fully inhibited by the broad-spectrum caspase inhibitor Z-VAD
      fmk. However, the caspase-3-specific inhibitor Z-DEVDfmk only partially inhibited
      apoptosis. This indicated that a second caspase is required in vivo for full
      activation of the apoptotic nucease CAD. Aurin tricarboxylic acid (ATA) did not
      inhibit VP-16-induced apoptosis. In contrast, apoptosis induced by
      hydroxychloroquine (HCQ) in HL-60 cells was caspase-3 independent and was fully
      inhibited by ATA. Thus, CAD does not appear to be involved in chromatin DNA
      degradation in this case. A second apoptotic nuclease is postulated to degrade
      the DNA, likely endo- exonuclease, an abundant nuclear enzyme that acts on both
      DNA and RNA and is present in latent form. HCQ, but not VP-16, stimulated DNA
      degradation ("laddering") in isolated nuclei. This indicates that the drug can
      act directly in the nuclei to trigger activation of the second latent apoptotic
      nuclease.

PMID- 11227494
TI  - PR-000350, a novel hypoxic radiosensitizer, enhances tumor cell killing by
      promoting apoptosis preferentially in the S-phase fraction.
AB  - PR-000350, a novel hypoxic radiosensitizer, is a 2-nitroimidazole nucleoside
      analog and has begun to be used for clinical cancer therapy. In this study, using
      U937 monoblastoid cells we investigated the mechanisms of enhanced cell killing
      by PR-000350. When cells were irradiated under an extremely hypoxic condition,
      the apoptotic rate was strongly suppressed. However, a remarkable increase in the
      DNA fragmentation rate as well as in the ladder formation was observed when
      hypoxic cells were irradiated in the presence of 5 mM PR-000350. DNA histograms
      of the PR-000350 treated group showed enhancement of the sub-G1 fraction and
      simultaneous suppression of the progression of the cell cycle from the S to G2/M
      phase at 4-8 h after X-irradiation, suggesting the importance of the S phase in
      the induction of apoptotic cell death. Flow cytometric and immunohistochemical
      analyses after BrdU labelling revealed that apoptotic cell death is induced
      mainly in the BrdU-positive cells. In addition, by using cell synchronization
      technique it was proved that the S phase is the most sensitive fraction to the
      radiosensitizing effect of PR-000350. These results suggest that PR-000350
      strongly enhances tumor cell killing by promoting X-ray induced-apoptosis
      preferentially in the S-phase fraction. PR-000350 is a new type radiosensitizer
      and promise to provide an effective anti-cancer activity against hypoxic tumor
      cells that are resistant to the usual radiotherapy.

PMID- 11227495
TI  - In vitro evaluation of GL331's cancer cell killing and apoptosis-inducing
      activity in combination with other chemotherapeutic agents.
AB  - GL331 is a novel podophyllotoxin-derived compound and is more efficacious than
      its congener VP-16 in killing several types of cancer cells, that has promoted
      considerable interest in its possibility of clinical use. In this study, we found
      that the higher cytotoxicity of GL331 in nasopharyngeal carcinoma NPC-TW01 cells
      was attributed to the elevated ability to induce apoptotic cell death. In
      addition to evaluation of GL331's single agent activity, the use of GL331 in
      combination with other established therapeutic agents was also evaluated. We
      found that GL331-induced cell cycle perturbation occurred upon initial 8-h
      exposure, and pretreatment of NPC-TW01 cells with GL331 for 8 h significantly
      interfered with the cytotoxicities of VP-16, cisplatin, 5-fluorouracil and
      adriamycin. When the schedule of drug administration was reversed, high-toxic
      concentrations of these agents revealed an antagonistic effect on GL331; however,
      their low-toxic doses had the additive or even more-than-additive effect on the
      cytotoxicity induced by GL331 at 0.1 microM or less, but for GL331 concentrations
      of greater than 1 microM, the effect became less than additive. These data
      suggest that overlapping mechanisms could be elicited by GL331 and other agents,
      and additional preclinical studies are needed to determine the optimal dose
      combination and administration schedule that will enhance, rather than interfere
      with, the efficacy of GL331 in combination with other anti-cancer agents.

PMID- 11227496
TI  - Edelfosine, apoptosis, MDR and Na+/H+ exchanger: induction mechanisms and
      treatment implications.

PMID- 11227497
TI  - Apoptosis in Alzheimer's disease--an update.
AB  - Alzheimer's disease (AD) is the most common human neurodegenerative disorder
      characterized by the progressive deterioration of cognition and memory in
      association with the presence of senile plaques, neurofibrillary tangles, and
      massive loss of neurons. Most cases of AD are late-onset and sporadic, but in
      some cases the disease is inherited as an autosomal dominant trait. Four
      different genes, the amyloid precursor protein, apolipoprotein E, and presenilins
      1 and 2 have been implicated in the etiology of familial AD. It is now generally
      accepted that massive neuronal death due to apoptosis is a commmon characteristic
      in the brains of patients suffering from neurodegenerative diseases, and
      apoptotic cell death has been found in neurons and glial cells in AD. This review
      summarizes the current findings regarding the evidence for apoptosis in AD and
      discusses the possible involvement of apoptosis-regulating factors in the
      pathology of AD. Modification of the apoptotic cascade could be considered as a
      primary therapeutic strategy for the disease.

PMID- 11227498
TI  - Stripping voltammetry in environmental and food analysis.
AB  - The review covers over 230 papers published mostly in the last 5 years. The goal
      of the review is to attract the attention of researchers and users to stripping
      voltammetry in particular, its application in environmental monitoring and
      analysis of foodstuffs. The sensors employed are impregnated graphite, carbon
      paste, thick film carbon/graphite and thin film metallic electrodes modified in
      situ or beforehand. Hanging mercury drop electrodes and mercury coated glassy
      carbon electrodes are also mentioned. Strip and long-lived sensors for portable
      instruments and flow through systems are discussed as devices for future
      development and application of stripping voltammetry.

PMID- 11227500
TI  - Plastic membrane electrode for the potentiometric determination of pethidine
      hydrochloride in pharmaceutical preparations.
AB  - A novel poly(vinyl chloride) membrane electrode with dibutyl phthalate as
      plasticizer based on the pethidine-tetraphenylborate ion-association complex as
      ion-exchange site for the determination of pethidine hydrochloride in injections
      and tablets was developed. A linear response for 1 x 10(-5) to 1 x 10(-2) mol/L
      drug with a slope of 51.77 mV/decade was established. The optimum pH range was 2
      8. The lower detection limit was 2.18 x 10(-6) mol/L. There were negligible
      interferences from a number of inorganic and organic cations and some common drug
      excipients. The electrode proposed had been successfully applied to determine
      pethidine hydrochloride in tablets and injections. The results correlated well
      with those obtained by the United States Pharmacopoeia standard procedure.

PMID- 11227501
TI  - Construction and analytical application of a biosensor based on stearic acid
      graphite powder modified with sweet potato tissue in organic solvents.
AB  - A biosensor based on stearic acid-graphite powder modified with sweet potato
      (Ipomoea batatas (L.) Lam.) tissue as peroxidase source was constructed and
      applied in organic solvents. Several parameters were studied to evaluate the
      performance of this biosensor such as stearic acid-graphite powder and tissue
      composition, type and concentration of supporting electrolyte, organic solvents,
      water/organic solvent ratio (% v/v) and hydrogen peroxide concentration. After
      selection of the best conditions, the biosensor was applied for the determination
      of hydroquinone in cosmetic creams in methanol. At the peroxidase electrode
      hydroquinone is oxidized in the presence of hydrogen peroxide and the radical
      formed was reduced back electrochemically at -180 mV vs Ag/AgCl (3.0 mol L(-1)
      KCl). The reduction current obtained was proportional to the concentration of
      hydroquinone from 6.2 x 10(-5) to 1.5 x 10(-3) mol L(-1) (r = 0.9990) with a
      detection limit of 8.5 x 10(-6) mol L(-1). The recovery of hydroquinone from two
      samples ranged from 98.8 to 104.1% and an RSD lower than 1.0% for a solution
      containing 7.3 x 10(-4) mol L(-1) hydroquinone and 1.0 x 10(-3) mol L(-1)
      hydrogen peroxide in 0.10 mol L(-1) tetrabutylammonium bromide methanol-phosphate
      buffer solution (95:5% v/v) (n = 10) was obtained.

PMID- 11227505
TI  - Isotope dilution inductively coupled plasma mass spectrometry (ID ICP-MS) for the
      certification of lead and cadmium in environmental standard reference materials.
AB  - Lead (Pb) and cadmium (Cd) have been determined in six new environmental standard
      reference materials (SRMs) using isotope dilution inductively coupled plasma mass
      spectrometry (ID ICP-MS). The SRMs are the following: SRM 1944, New York-New
      Jersey Waterway Sediment, SRMs 2583 and 2584, Trace Elements in Indoor Dust,
      Nominal 90 mg/kg and 10,000 mg/kg Lead, respectively, SRMs 2586 and 2587, Trace
      Elements in Soil Containing Lead from Paint, Nominal 500 mg/kg and 3,000 mg/kg
      Lead, respectively, and SRM 2782, Industrial Sludge. The capabilities of ID ICP
      MS for the certification of Pb and Cd in these materials are assessed. Sample
      preparation and ratio measurement uncertainties have been evaluated.
      Reproducibility and accuracy of the established procedures are demonstrated by
      determination of gravimetrically prepared primary standard solutions and by
      comparison with isotope dilution thermal ionization mass spectrometry (ID TIMS).
      Material heterogeneity was readily demonstrated to be the dominant source of
      uncertainty in the certified values.

PMID- 11227506
TI  - Matrix interferences in the determination of trace elements in waste waters by
      inductively coupled plasma atomic emission spectrometry with ultrasonic
      nebulization.
AB  - The use of inductively coupled plasma atomic emission spectrometry with
      ultrasonic nebulization (USN-ICP-AES) for determining Ag, Al, As, Ba, Bi, Cd, Co,
      Cr, Cu, Fe, Hg, Mg, Mn, Ni, Pb, Sb, Sr, V and Zn in complex matrices of Ca, Na, K
      and P in waste waters is described. Generally, depressions in the analyte
      emission intensity occur in the presence of concomitants. Matrix interferences
      can be minimized by increasing the operating power and lowering the carrier gas
      flow rate. However, the enhancement of the signal-to-background ratios (SBRs)
      shows an opposite trend. Therefore, routine analyses were performed at a
      compromise power setting of 1,350 W, a carrier gas flow rate of 0.8 L min(-1) and
      an observation height of 14 mm above the load coil and using a matrix matched
      calibration procedure. Limits of detection (LODs) at chosen operating conditions
      were at microg L(-1) levels for most of the elements studied, including mercury
      when KBr is added to the analyte solution to enhance sensitivity. LODs were not
      significantly changed in the presence of matrix elements. Recoveries for the
      majority of added elements from spiked waste water samples are between 93 and
      105% using a matrix matched calibration.

PMID- 11227507
TI  - Extraction of PCDD/PCDF from soil with supercritical CO2: optimization by a three
      level factorial design approach.
AB  - Two factors (pressure and temperature) varied over three levels were optimized
      for the extraction of PCDD/F from native contaminated soil with toluene-modified
      supercritical carbon dioxide. Temperature had a strong positive effect on the
      recovery. The most efficient extraction was achieved at 120 degrees C. This is in
      contrast to the influence of the temperature on the extraction of HCH, where a
      higher recovery is obtained at 60 degrees C than at 150 degrees C. The optimized
      conditions found for this soil were applied to the analysis of a BCR (European
      Commission) reference material prepared from contaminated industrial soil. The
      results are in good agreement with those of an interlaboratory study.

PMID- 11227508
TI  - Determination of delta4-3-ketosteroids based on oxime formation by difference
      circular dichroism spectroscopy.
AB  - delta4-3-Ketosteroids exhibit an intensive negative Cotton effect on the circular
      dichroism (CD) spectra in the wavelength range for the n-pi* electronic
      transition (270-350 nm). With hydroxylamine hydrochloride, delta4-3-ketosteroid
      compounds can be transformed into oxime derivatives. Following oxime formation,
      positive ellipticity with low intensity can be registered in this wavelength
      range. The quantitative determination of delta4-3-ketosteroids is based on the
      considerable difference between the ellipticities before and after oxime
      formation. The difference ellipticity for the six ketosteroids examined
      (norethisterone, levonorgestrel, levonorgestrel acetate, methyltestosterone,
      testosterone phenylpropionate, nortestosterone phenylpropionate) varies linearly
      with the concentration in the interval 6 x 10(-6)-3 x 10(-3) mol/L. The method
      can be well applied to determination of delta4-3-ketosteroid contamination of
      norgestimate [(+)-13-ethyl-17-hydroxy-18,19-dinor-17alpha-pregn4-en-20-yn-3-one
      oxime acetate]; 0.02-10% impurity can be measured.

PMID- 11227512
TI  - On the presence of PCDD/Fs and other chlorinated hydrocarbons in the second
      generation of the European Reference Soil Set--the EUROSOILS.
AB  - The second generation of the European Reference Soil-Set, the so-called
      EUROSOILS, has been introduced recently. The presence of organic micro-pollutants
      in this new type of reference materials has already been studied for polycyclic
      aromatic hydrocarbons, triazines, phenylureas and other pesticides. The already
      large amount of data concerning the level of different contaminants, the
      elemental composition and matrix properties is completed by a survey by means of
      GC/MS on the polychlorinated dibenzodioxins/furans (PCDD/Fs) and other
      chlorinated hydrocarbons. Higher concentrations for 4,4'-DDT in EUROSOIL 2 (10.57
      +/- 0.02 ng/g), for dieldrin in EUROSOIL 3 (8.85 +/- 0.87 ng/g) and for
      heptachlor-epoxide in EUROSOIL 4 (5.86 +/- 0.16 ng/g) could be detected. Sum
      concentrations for PCDD/Fs were 15.02 ng/kg (EUROSOIL 1), 214.29 ng/kg (EUROSOIL
      2), 873.32 ng/kg (EUROSOIL 3), 54.47 ng/kg (EUROSOIL 4) and 119.61 ng/kg
      (EUROSOIL 5).

PMID- 11227513
TI  - Sonoelectroanalytical detection of lead at a bare copper electrode.
AB  - The sonochemically facilitated, mercury free detection of Pb2+ at a copper
      electrode has been investigated as a means of simplifying the quantification of
      this important analyte and to minimise the interference of copper ion. The
      procedure relies upon maximising the formation of Pb-Cu intermetallic compounds
      leading to the emergence of a single, easily quantifiable stripping signal.
      Linear responses to Pb2+ were obtained with a sensitivity comparable to that
      obtained at a bare glassy carbon electrode. Interference from Cu2+, Zn2+ and Cd2+
      was assessed on the copper electrode with no appreciable change in the Pb2+
      voltammetric profile observed. In contrast, bare glassy carbon showed a
      significant change in Pb2+ voltammetric profile as Cu2+ was added, due to the
      formation of intermetallic species.

PMID- 11227516
TI  - Flame atomic absorption spectrometric determination of trace chromium in various
      standard samples after preconcentration with 2-(5-bromo-2-pyridylazo)-5
      diethylaminophenol.
AB  - Chromium can be quantitatively retained as 2-(5-bromo-2-pyridylazo)-5
      diethylaminophenol (5-Br-PADAP)-tetra-phenylborate(TPB) complex onto
      microcrystalline naphthalene in the pH range 4.8-5.9 from a large volume of
      aqueous solutions of various standard samples. After filtration, the solid mass
      consisting of the chromium complex and naphthalene was dissolved with 5 mL of
      dimethylformamide and the metal was determined by air-acetylene FAAS. A detection
      limit of 4 ng/mL for chromium was established. The interference of a large number
      of anions and cations has been studied and the optimized conditions developed
      were utilized for the trace determination of chromium in various standard alloys
      and biological samples.

PMID- 11227517
TI  - Phenylacetylene as a new surrogate standard for the determination of BTEX by
      GC/FID.
AB  - Benzene, toluene, ethylbenzene, xylene (short form: BTEX) and other monoaromatic
      compounds are environmental contaminants which are often analyzed by GC/FID. For
      the calculation of BTEX concentrations in water samples normally external
      quantification with defined BTEX solutions is sufficient. However, for accurate
      quantification of BTEX in complex matrices it is necessary to use internal
      standards, e.g. 1-chlorohexane. Isotopes of BTEX are usually the best alternative
      but they are only applicable to GC/MS, because their retention times are similar
      to the original BTEX. 1-Chlorohexane and phenylacetylene were compared with
      respect to their quality as internal standards. Good results were obtained with
      the monoaromatic phenylacetylene as a surrogate standard. The physical properties
      of phenylacetylene are very similar to BTEX species and it normally does not
      occur in environmental samples. 1-Chlorohexane was more strongly adsorbed on the
      used soil than BTEX during sample preparation. This fact suggests that the single
      aromatic rings of BTEX and phenylacetylene are mainly responsible for the
      adsorption behavior.

PMID- 11227518
TI  - Determination of nicotinamide (NA) using its polarographic catalytic wave in the
      presence of KIO3.
AB  - Nicotinamide (NA) yields a polarographic catalytic wave with a peak potential 
      1.38 V (vs. SCE) in 0.1 mol/L HAc-NaAc (pH 4.7)/4 x 10(-3) mol/L KIO3 buffer
      solution. The sensitivity of the catalytic wave increased in one order of
      magnitude as compared to that of the responding reduction wave without KIO3.
      Based on this observation, a new method for the determination of NA was
      recommended. The second order derivative peak current was proportional to the NA
      concentration in the range of 5 x 10(-8)- 6 x 10(-7) mol/L. 0.11-fold vitamin B1,
      0.13-fold B2, 0.14-fold B6 and 8-fold nicotinic acid amounts do not interfere the
      determination of 1 x 10(-6) mol/L NA. The proposed method was used to determine
      the NA content in multivitamin tablets, with good agreement to the declared
      amount.

PMID- 11227519
TI  - A flow injection chemiluminescence system for the determination of isoniazid.
AB  - A chemiluminescence (CL) flow system is described for the determination of
      isoniazid based on its enhancement on the chemiluminescence (CL) emission
      produced upon mixing a hexacyanoferrate(III) solution with an alkaline luminol
      solution. The system responds linearly to isoniazid concentration in the range 0
      1 mg/L with a detection limit (3sigma) of 0.03 microg/L, relative standard
      deviation (RSD) of 1.2% for 0.1 mg/L isoniazid (n = 11). The system has been
      successfully applied to the determination of isoniazid in pharmaceutical
      preparations.

PMID- 11227525
TI  - Study of the binding characteristics of molecular imprinted polymer selective for
      cefalexin in aqueous media.
AB  - A molecularly imprinted polymer was prepared using cefalexin as the template
      molecule and 2-(trifluoromethyl)acrylic acid as the functional monomer. The bulk
      polymer was ground, sieved and investigated in an equilibrium binding experiment
      to evaluate the binding characteristics of the cefalexin-imprinted polymer for a
      better understanding of the mechanisms of recognition in molecularly imprinted
      polymers. Scatchard analysis showed that two classes of binding sites were formed
      in the imprinted polymer under the concentration studied. The dissociation
      constants were estimated to be 0.14 mmol/L and 2.38 mmol/L. The polymer gave much
      higher binding capacity for cefalexin than the non-imprinted polymer with the
      same chemical composition. The selectivity was evaluated by distribution
      coefficients of cefalexin and other structurally similar compounds. The results
      showed that the imprinted polymer exhibited high affinity for cefalexin among the
      tested compounds.

PMID- 11227526
TI  - Amperometric sensor for L-ascorbic acid determination based on MnO2 bulk modified
      screen printed electrode.
AB  - A simple biosensor constructed by bulk-modification of carbon ink with manganese
      dioxide as a mediator was investigated for its ability to serve as amperometric
      detector for L-ascorbic acid in hydrodynamic mode. The sensor could be operated
      at pH 5.0 (0.05 M phosphate buffer) and exhibited excellent reproducibility and
      stability. Optimization of measurement parameters such as applied working
      potential and pH value were studied in detail. The screen printed electrode
      exhibited a linear amperometric increase with the concentration of L-ascorbic
      acid from 50 mg L(-1) to 250 mg L(-1) and gave a (LOD = 3sigma) detection limit
      of 0.2 mg L(-1) (1.172 micromol L(-1)). The manganese dioxide modified screen
      printed electrode shows long term stability.

PMID- 11227527
TI  - Stability of inorganic mercury and methylmercury on yeast-silica gel
      microcolumns: field sampling capabilities.
AB  - The stability of methylmercury and inorganic mercury retained on yeast-silica gel
      microcolumns was established and compared with the stability of these species in
      solution. Yeast-silica gel columns with the retained analytes were stored for two
      months at three different temperatures: -20 degrees C, 4 degrees C and room
      temperature. At regular time intervals, both mercury species were eluted and
      quantified by cold vapor atomic absorption spectrometry (CVAAS). Methylmercury
      was found stable in the columns over the two-month period at the three different
      temperatures tested while the concentration of inorganic mercury decreased after
      one week's storage even at -20 degrees C. These results are of great interest
      since the use of these microcolumns allows the preconcentration and storage of
      mercury species until analysis, thus saving laboratory space and avoiding the
      problems associated with maintaining species integrity in aqueous solution.

PMID- 11227530
TI  - Speciation of major arsenic species in seawater by flow injection hydride
      generation atomic absorption spectrometry.
AB  - Arsenic present at 1 microg L(-1) concentrations in seawater can exist as the
      following species: As(III), As(V), monomethylarsenic, dimethylarsenic and unknown
      organic compounds. The potential of the continuous flow injection hydride
      generation technique coupled to atomic absorption spectrometry (AAS) was
      investigated for the speciation of these major arsenic species in seawater. Two
      different techniques were used. After hydride generation and collection in a
      graphite tube coated with iridium, arsenic was determined by AAS. By selecting
      different experimental hydride generation conditions, it was possible to
      determine As(III), total arsenic, hydride reactive arsenic and by difference non
      hydride reactive arsenic. On the other hand, by cryogenically trapping hydride
      reactive species on a chromatographic phase, followed by their sequential release
      and AAS in a heated quartz cell, inorganic As, MMA and DMA could be determined.
      By combining these two techniques, an experimental protocol for the speciation of
      As(III), As(V), MMA, DMA and nonhydride reactive arsenic species in seawater was
      proposed. The method was applied to seawater sampled at a Mediterranean site and
      at an Atlantic coastal site. Evidence for the biotransformation of arsenic in
      seawater was clearly shown.

PMID- 11227528
TI  - A sequential injection cold-vapor atomic absorption method for the determination
      of total mercury.
AB  - A sequential injection (SI) method for the determination of mercury via cold
      vapor atomic absorption spectrophotometry is presented. The method differs from
      flow injection (FI) cold vapor methods for the determination of mercury because
      of the simplicity of the system required for the method: one pump, one valve, a
      gas-liquid separator, and an atomic absorption spectrophotometer equipped with a
      quartz cell. Under optimal conditions, the method has the following figures of
      merit: a linear calibration range of 1.0 to 20 microg L(-1); a detection limit of
      0.46 microg L(-1); and a precision of 0.90% RSD (8 microg L(-1)). The procedure
      allows for a sampling rate of one injection per 80 s (excluding sample
      pretreatment). Results from the determination of mercury in water and fish
      specimens are also presented. The figures of merit of the method are compared to
      two other SI methods for the determination of mercury.

PMID- 11227531
TI  - Determination of trace elements including platinum in tree bark by ICP mass
      spectrometry.
AB  - The increasing emission of Pt-group metals from automobile catalytic converters
      requires the development of highly sensitive procedures for ultratrace analysis
      of environmental and biological systems. Tree bark, located close to motorway or
      industrial areas, was utilised as a substrate for collection of airborne
      particulate matter and samples after digestion (microwave assisted dissolution
      with HNO3 and HCl) were analysed by ICP mass spectrometry. The study targeted Pt
      and other metallic contaminants and involved analysis of some 57 tree bark
      samples using both quadrupole and double-focusing sector field ICP mass
      spectrometers. Detection limits for platinum determination in tree bark were 0.03
      ng/g (DF-ICP-MS) and 0.2 ng/g (ICP-QMS). The platinum content of the bark samples
      ranged from 0.07-5.4 ng/g.

PMID- 11227532
TI  - Individual sample conditioning in flow analysis. Determination of N-total in
      plant materials.
AB  - A flow-batch system allowing in-line individual sample matrix matching is
      proposed for analysis of sample lots with high variability in acidity. The
      feasibility of the approach is demonstrated in the spectrophotometric
      determination of total nitrogen in Kjeldahl digests, using a column with a
      slightly soluble reagent (AgCl). The solutions are sequentially injected by means
      of an 8-port selecting valve and processed in a mixing chamber that is also used
      as a monitoring unit. The system yields reproducible results (r.s.d. usually <
      2.5%) and the sampling rate is 14 samples/h. The analytical curve is linear
      within 1.00 and 6.00% N (dry basis), and the regression coefficient is > 0.999 (n
      = 6). Results are in agreement with certified values of standard reference
      materials and with results obtained by conductometry.

PMID- 11227533
TI  - A highly sensitive fluorimetric method for the determination of fluoride in
      biological material with Al3+-calcein complex.
AB  - A highly sensitive fluorimetric method for the determination of fluoride was
      established. The method was based on quenching of the fluorescence of the Al3+
      calcein complex in CCl3COOH-CH3COOK buffer solution by fluoride. The fluorescence
      emission was measured at lambdaex/lambdaem 480/503 nm, and the experimental
      variables and interference in this determination were studied. The linear
      calibration range was 0.8 ng/mL to 150 ng/mL and the detection limit was 0.2
      ng/mL. The method was applied to determine fluoride in biological materials. The
      recovery was in the range of 96.3% to 104.7% and the relative standard deviation
      was 4.6%. The results obtained from the certified reference material by the
      present method agreed with the certified values.

PMID- 11227534
TI  - Direct determination of 1-naphthoxylactic acid in biological fluids by non
      protected fluid room temperature phosphorimetry.
AB  - A selective and sensitive room-temperature phosphorimetric method for the direct
      determination of 1-naphthoxylactic acid (NA) in biological fluids is described.
      It is based on obtaining a phosphorescence signal from NA using TlNO3 as a heavy
      atom perturber and Na2SO3 as a deoxygenator without a protective medium. This
      technique is named non-protected room-temperature phosphorescence (NP-RTP), which
      allows to determine analytes in complex matrices without the need for tedious
      prior separation. Optimization of the operational conditions resulted in a
      detection limit for NA of 9.6 ng/mL according to the error propagation theory.
      The repeatability and standard deviation were also determined. This method was
      successfully applied to the determination of NA in urine and human serum.

PMID- 11227536
TI  - Determination of direct-bilirubin by a fluorimetric-enzymatic method based on
      bilirubin oxidase.
AB  - A method for the determination of direct bilirubin by reaction with bilirubin
      oxidase (BOx) is reported. The procedure is based on the changes in fluorescence
      which take place during the enzymatic reaction of BOx with any of the three forms
      of bilirubin (free, conjugated and with albumin) when the solution is excited at
      240 nm and the emission is measured at 440 nm. The change in fluorescence was
      studied thoroughly. It seems mainly due to the fluorescence of one of the
      reaction products. A theoretical study was carried out to relate the changes in
      fluorescence observed to the species taking part in the reaction and to establish
      some of the enzymatic reaction constants. The optimum reaction conditions were
      studied for each of the three types of bilirubin together with their analytical
      characteristics (linear range and precision). Selective determination of direct
      bilirubin was carried out for various synthetic samples with good results. A
      linear response up to 7 mg L(-1) of direct bilirubin was obtained. Using optimum
      conditions, the precision for free and conjugated bilirubin was 3.4% (n = 5) and
      3.0% (n = 5), respectively.

PMID- 11227535
TI  - A novel method for the determination of total protein in human serum by near
      infrared fluorescence recovery.
AB  - A novel fluorometric method has been developed for the determination of total
      protein in human serum with a new near-IR reagent as a fluorescence probe, based
      on the fluorescence recovery of the cyanine-CTAB system in the presence of
      protein. Maximum fluorescence is produced with maximum excitation and emission
      wave-lengths at 765 and 812 nm, respectively. Under optimal conditions, the
      calibration graphs are linear over the range 0.4-12.0 microg/mL for protein. The
      detection limit is 70 ng/mL, and the relative standard deviation of six replicate
      measurements is 1.14% for 6.0 microg/mL protein. The results are satisfactory.

PMID- 11227538
TI  - Modified on-line monitoring of total gaseous mercury in flue gases using Semtech
      Hg 2000 analyzer.
AB  - The Semtech Hg 2000 analyzer continuously monitors the Hg0 content in flue gas.
      An on-line measurement method of total gaseous mercury in flue gas developed in
      our laboratory is described, which uses the absorption cell of the Semtech Hg
      Analyzer connected to a converter that is located in a furnace heated up to 650
      degrees C. The converter can be heated up to 800 degrees C by both the furnace
      and an extra heating of a Ni-Cr alloy heating wire. Both the absorption cell and
      the converter are made of quartz. All gaseous Hg2+ species in flue gas are
      thermally reduced to Hg0 by the converter and detected by the Semtech Hg 2000
      analyzer. The thermal reduction efficiencies of different conversion materials,
      which were filled in the converter, such as quartz chips, granular MgO, Ni and
      CoO powder, were tested using different flue gas conditions. Studies have shown
      that HCI is the major factor to inhibit the thermal reduction of Hg2+ to Hg0, and
      in the converter and the absorption cell Hg0 will react readily with HCl to form
      HgCl2. Both MgO and Ni could be used in the converter to absorb HCl in the flue
      gas, but Ni has better absorption efficiency. By using an original Semtech and a
      modified one, both Hg0 and total gaseous Hg contents in flue gas could be
      monitored simultaneously and continuously.

PMID- 11227539
TI  - Development and validation of a near infrared method for the analytical control
      of a pharmaceutical preparation in three steps of the manufacturing process.
AB  - A near infrared diffuse reflectance spectroscopy (NIRS) procedure for the
      quantitative control analysis of the active compound (otilonium bromide) in a
      pharmaceutical preparation in three steps of the production process (blended
      product, cores and coated tablets) and a methodology for its validation are
      proposed. The analytical procedure is composed by two consecutive steps. First,
      the sample is identified by comparing its spectrum with a second derivative
      spectral library. If the sample is positively identified, the active compound is
      quantified by using a previously established partial least squares (PLS)
      calibration model. The procedure was validated by studying repeatability,
      intermediate precision, accuracy and linearity. To this end, an adaptation of ICH
      (International Conference on Harmonisation) validation methodology to an NIR
      multivariate calibration procedure is proposed. The relative standard error of
      prediction (RSEP) was < or = 1% and the suitability of the procedure for control
      analysis was confirmed by the results obtained analysing new production samples
      produced over a three-month period.

PMID- 11227540
TI  - Application of HPLC-NMR coupling using C30 phase in the separation and
      identification of flavonoids of taxonomic relevance.
AB  - The on-line separation and identification of two important taxonomic markers for
      plant species of the Paepalanthus genus, the flavonoids 6-methoxykaempferol-3-O
      beta-D-glucopyranoside and 6-methoxykaempferol-3-O-beta-D-6"(p
      coumaroyl)glucopyranoside, has been performed with an HPLC-NMR coupling using C30
      phase. 1D spectra have been recorded in the stopped-flow mode for the two
      predominant chromatographic peaks. This is the first application of HPLC-NMR
      coupling using C30 phase to a taxonomic problem. The technique drastically
      reduces the required amount of sampling for structure determination.

PMID- 11227541
TI  - Fiber-in-tube solid-phase microextraction: a fibrous rigid-rod heterocyclic
      polymer as the extraction medium.
AB  - A novel "fiber-in-tube" configuration has been applied to the extraction tube of
      solid phase microextraction (SPME), and the direct coupling of the extraction
      process to liquid chromatography (LC) has been accomplished for the analysis of n
      butylphthalate in wastewater. By using this fiber-in-tube SPME/LC system the
      preconcentration factor for the phthalate was about 160 with 20 min extraction
      and no interference peak was observed in the chromatogram. The results also
      showed the potential applications of this fiber-in-tube SPME/LC for the analysis
      of sub-ppb level (i.e., lower than 1 ng/mL) of various organic analytes in
      aqueous sample matrix without a large solvent consumption during the
      preconcentration process.

PMID- 11227542
TI  - Comparison of different excitation methods for X-ray spectral analysis: the case
      of synchrotron radiation.
AB  - Different excitation means, protons, photons and electrons (PIXE, XRFA, and EPMA,
      respectively) have previously been compared with regard to the figures of merit,
      i.e. detection power, precision and accuracy. The aim in this article is to
      compare synchrotron radiation SR as another excitation method with the methods
      mentioned above. From this point of view the evaluation of (SR) was missing as an
      again independently optimized excitation method and was based as previously on
      practical problems of trace analysis, in this case on the determinations of
      traces in lead. The experiment has been performed with thick homogeneous samples
      of lead, the same samples already used in the former work, so that a direct
      comparison is possible. The calculation of the figures of merit is based on the
      measurements of the blank values and their relative standard deviation for the
      detection limit and on the random errors for the precision. Regarding the thick
      homogeneous target of lead XRFA still turns out to be the best method, whereas
      Synchrotron X-Ray Fluorescence SY-XRF compares favorably, at least for larger
      atomic numbers Z. Even PIXE is inferior to (SY-XRF) in the case of larger Z; when
      information on the lateral distribution of the elements is of interest, PIXE is
      indispensable.

PMID- 11227543
TI  - Determination of Cd and Pb at microg/L levels by HHPN-beam injection flame
      furnace-AAS.
AB  - Flame-heated tubes are widespread in flame-AAS, mainly for the determination of
      hydride-forming elements. Instead of the introduction of gaseous compounds
      liquids can also be introduced continuously in such an absorption cell. With the
      aid of an HPLC pump the liquid is forced through a very fine nozzle, generating
      an aerosol beam less than 0.5 mm in diameter. This beam travels a distance of
      10cm as a "free-flying aerosol jet" into the sample introduction hole of a metal
      tube furnace placed in the flame. Both introduction of the entire sample and the
      long residence time lead to a considerable improvement in power of detection. The
      detection limit for 100 microL samples amounts to 7 microg/L (Pb) and to 0.2
      microg/L (Cd), which means an increase in power of detection of between one and
      two orders of magnitude compared to conventional flame-AAS. The relative standard
      deviation (100 microL sample volume, N = 10) was found to be 1.3% (signal area)
      for 600 microg/L Pb and to be 1.5% (signal-area) for 15 microg/L Cd. RSD values
      from measurements in peak-height amounted to 2.2% (Pb) and to 1.7% (Cd).

PMID- 11227544
TI  - Measurements for certification of chlortetracycline reference materials within
      the European Union Standards, Measurements and Testing programme.
AB  - The experimental design of a material certification programme is described. The
      matrix reference materials (RMs) comprised chlortetracycline (CTC)-containing and
      CTC-free lyophilised porcine liver, kidney and muscle produced under the European
      Commission's Standards Measurements and Testing (SMT) programme. The aim of the
      certification programme was to determine accurately and precisely the
      concentration of CTC and 4-epi-chlortetracycline (epi-CTC) contained in the RMs.
      A multi-laboratory approach was used to certify analyte concentrations.
      Participants (n = 19) were instructed to strictly adhere to previously
      established guidelines. Following the examination of analytical performance
      criteria, statistical manipulation of results submitted by 13 laboratories, (6
      withdrew) allowed an estimate to be made of the true value of the analyte
      content. The Nalimov test was used for detection of outlying results. The Cochran
      and Bartlett tests were employed for testing the homogeneity of variances. The
      normality of results distribution was tested according to the Kolmogorov-Smirnov
      Lilliefors test. One-way analysis of variance (ANOVA) was employed to calculate
      the within and between-laboratory standard deviations, the overall mean and
      confidence interval for the CTC and epi-CTC content of each of the RMs. Certified
      values were within or very close to the target concentration ranges specified in
      the SMT contract. These studies have demonstrated the successful production and
      certification of CTC-containing and CTC-free porcine RMs.

PMID- 11227545
TI  - Investigations on the water content of candidate reference material CRM 679
      cabbage powder.
AB  - The determination of the residual water content by thermal methods and especially
      by Karl Fischer titration in a candidate reference material of the European
      Commission (candidate CRM 679 cabbage powder) is described and discussed.

PMID- 11227546
TI  - Rapid simultaneous determination of four anthracene derivatives using a single
      non-linear variable-angle synchronous fluorescence spectrum.
AB  - A rapid, simple and inexpensive spectrofluorimetric method has been developed for
      the simultaneous identification and quantification of anthracene (ANT), 9,10
      dimethylanthracene (DIM), 2-aminoanthracene (AMI) and dibenz[ah]anthracene (DIB).
      A well-resolved spectrum for the mixture of these four compounds is obtained
      based on a single non-linear variable-angle synchronous scanning. The linear
      concentration ranges are 10-1,000, 5-500, 50-1,000 and 10-200 ng mL(-1) for ANT,
      DIM, AMI and DIB, respectively, at lambdaex/lambdaem = 358/380, 399/408, 414/465
      and 298/394 nm, respectively. The analyses are performed in cyclohexane.
      Recoveries of 90.0-111.0% in synthetic mixtures are obtained. The detection
      limits are 2.0 ng mL(-1) for DIM, 2.7 ng mL(-1) for ANT, 15.8 ng mL(-1) for AMI
      and 4.2 ng mL(-1) for DIB. The method has also been applied to several real water
      samples with satisfactory results.

PMID- 11227547
TI  - The stability of non-ionic surfactants and linear alkylbenzene sulfonates in a
      water matrix and on solid-phase extraction cartridges.
AB  - The stability of nonylphenol ethoxylates (NPEO), alcohol ethoxylates (AEO),
      coconut diethanol amides (CDEA) and linear alkylbenzene sulfonates (LAS) in a
      water matrix and preconcentrated on SPE cartridges was studied. A stability study
      was carried out in a water matrix (spiked ground water and real-world waste
      water) comparing different pretreatment procedures (addition of sulfuric acid to
      pH = 3, preservation with 1% and 3% of formaldehyde). When stored in a water
      matrix serious qualitative and quantitative changes occurred in waste water
      during the period of time studied (30 days). The losses of C12-C14 alcohol
      ethoxylates ranged from 72% to 88% when the sample was preserved with acid and
      from 17% to 86% when the sample was preserved with formaldehyde (3%).
      Simultaneously, an enrichment of the shorter alkyl chain homologues (C7EO and
      C10EO) was observed. The losses of NPEO were from 45% (sample preserved by
      acidification or by addition of 3% of formaldehyde) to 85% (sample preserved with
      1% of formaldehyde). Additionally, an increase in concentration of polyethylene
      glycols (PEGs) and formation of different acidic forms, such as monocarboxylated
      (MCPEGs) and dicarboxylated polyethylene glycols (DCPEGs) were observed. The
      stability of surfactants preconcentrated on SPE cartridges was studied as a
      function of storage time and storage conditions (room temperature, 4 degrees C
      and -20 degrees C). The results indicate that disposable SPE cartridges can be
      recommended for the stabilization of non-ionic surfactants and LAS. Storage at 
      20 degrees C is feasible for long periods (up to 3 months for ground water and up
      to 2 months for waste water), while storage at 4 C can be recommended for a
      maximum of 1 month. When cartridges were kept at -20 degrees C the losses of AEOs
      (n = 12, 13 and 14), preconcentrated from waste water, ranged from 17 to 29%
      (after 60 days) and other compounds suffered small losses (maximum of 14% for
      C13LAS). At room temperature, after 7 days, the losses were less than 11%,
      indicating that shipping of samples by mail can be done without any special
      requirements.

PMID- 11227548
TI  - Microwave assisted methodology for the determination of organic pollutants in
      organic municipal wastes and soils: extraction of polychlorinated biphenyls using
      heat transformer disks.
AB  - Known benefits of microwave assisted extraction (MAE) of polychlorinated
      biphenyls (PCB) from solid matrices could be proven by the described approach
      using n-heptane as solely applied extraction solvent. Heat transfer within the
      extraction vessels was achieved by heat transformer disks which absorb microwave
      energy and transform it into heat rapidly and independently of the temperature
      present in the sample-solvent system. Disadvantageous co-extraction of polar
      substances could be ruled out and thus clean-up of the samples was simplified and
      sufficient for subsequent GC-MS analysis. Comparison with other extraction
      techniques confirmed the efficiency of this method also for aged samples.

PMID- 11227549
TI  - Characterization of aquatic humic substances and their metal complexes by
      immobilized metal-chelate affinity chromatography on iron(III)-loaded ion
      exchangers.
AB  - The analytical fractionation of aquatic humic substances (HS) by means of
      immobilized metal-chelate affinity chromatography (IMAC) on metal-loaded
      chelating ion exchangers is described. The cellulose HYPHAN, loaded with
      different trivalent ions, and the chelate exchanger Chelex 100, loaded to 90% of
      its capacity with Fe(III), were used. The cellulose HYPHAN, loaded with 2%
      Fe(III), resulted in HS distribution coefficients Kd of up to 10(3.7) mL/g at pH
      4.0 continuously decreasing down to 10(1.5) at pH 12, which were appropriate for
      HS fractionation by a pH-depending chromatographic procedure. Similar
      distribution coefficients Kd were obtained for HS sorption onto Fe(III)-loaded
      Chelex 100. On the basis of Fe-loaded HYPHAN both, a low-pressure and high
      pressure IMAC technique, were developed for the fractionation of dissolved HS
      applying a buffer-based pH gradient for their gradual elution between pH 4.0 and
      12.0. By coupling the Chelex 100 column under high-pressure conditions with an
      inductively coupled plasma mass spectrometer an on-line characterization of HS
      metal species could be achieved. Using these fractionation procedures a number of
      reference HS were characterized. Accordingly, the HA (humic acids) and FA (fulvic
      acids) studied could be discriminated into up to 6 fractions by applying
      cellulose HYPHAN, significantly differing in their Cu(II) complexation capacity
      but hardly in their substructures assessed by conventional FTIR. In the case of
      using Chelex 100 exchanger resin two major UV active HS fractions were obtained,
      which significantly differ in their complexation properties for Cu(II) and
      Pb(II), respectively.

PMID- 11227550
TI  - Rapid determination of PAHs in soil samples by HPLC with fluorimetric detection
      following sonication extraction.
AB  - A rapid method for the determination of PAHs in soil samples based on their
      extraction with methylene chloride by sonication and subsequent separation by
      HPLC with fluorimetric detection is proposed. A Hypersil Green PAH column was
      used with a gradient of acetonitrile/water as the mobile phase, together with a
      program of nine excitation and emission wavelength pairs. Recoveries were in the
      range 70-98%, except for acenaphthene and naphthalene, at concentration levels
      1.08-442 microg/kg with relative standard deviations in the range 2-15% (n = 4).
      Total PAHs found in soil samples were in the range 15-282 microg/kg. The results
      were compared with those obtained by applying the 3540 EPA method for two
      samples.

PMID- 11227551
TI  - Extraction of antimony and arsenic from fresh and freeze-dried plant samples as
      determined by HG-AAS.
AB  - Six extraction media (acetic acid, EDTA, tetrabutylammonium hydroxide, NaOH,
      MeOH/H2O, acetonitrile/H2O) were tested for their ability to extract antimony
      (Sb) and arsenic (As) from freeze-dried poplar leaves, pine shoots and spruce
      shoots, as well as from a peat matrix. Additionally, the extraction efficiency of
      Sb and As in fresh and freeze-dried elder leaves and poplar leaves was compared.
      Total concentrations of Sb and As of aliquots (approximately 220 mg) of the
      freeze-dried samples were analysed by flow injection hydride generation atomic
      absorption spectrometry (FI-HG-AAS) after open vessel digestion with adequate
      mixtures of nitric, sulfuric, hydrochloric, and perchloric acid. Three reference
      materials GBW 07602 Bush Branches and Leaves, GBW 07604 Poplar Leaves, and SRM
      1575 Pine Needles were analysed with every batch of samples to ensure the
      accuracy and precision of the applied analytical procedures. The use of
      hydrofluoric acid in the digestion mixture leads to distinctly lower As values
      (down to 40%) than actual concentrations in the investigated plant materials.
      Extraction efficiencies were generally low and lower for Sb than for As.
      Solutions of 0.66 mol L(-1) NaOH liberated highest amounts of Sb with
      approximately 10% for poplar leaves, and approximately 19% each for pine shoots
      and spruce shoots. Distinctly higher concentrations of As in NaOH extracts of
      poplar leaves (22%), pine shoots (32%), and spruce shoots (36%) were quantified.
      Extraction experiments resulted in yields of 7-9% from fresh elder and poplar
      leaves, respectively, and 8-13% for freeze-dried samples for Sb. The
      corresponding values for As were 10-35% for the fresh material and 7-37% for the
      freeze-dried samples.

PMID- 11227552
TI  - High resolution inductively coupled plasma mass spectrometry (HR-ICPMS)
      determination and multivariate evaluation of 10 trace elements in mussels from 7
      sites in Limfjorden, Denmark.
AB  - The contents of V, Cr, Co, Ni, Cu, Ga, Rb, Cd, Ba, and Pb in the soft tissue of
      blue mussel (Mytilus edulis) were determined by a high resolution inductively
      coupled plasma mass spectrometry (HR-ICPMS) method. Sample digestions were
      performed in closed microwave vessels using nitric acid and hydrogen peroxide.
      Using HR-ICPMS it is possible to resolve the analytical peaks from otherwise
      interfering polyatomic ions with a mass resolution setting of 4,000 (Cr, Ni, Cu).
      The proposed method was validated using a mussel tissue reference material (NIST
      SRM 2974). The proposed method was applied to real samples of blue mussel from
      seven sites in the inlet "Limfjorden", Denmark, and the levels of trace elements
      found were compared with the levels found in an earlier study. For the mussel
      samples large inter-regional differences in trace element concentrations in the
      tissues were recorded. The mussels from the different sites could be separated
      using principal component analysis (PCA). Comparison with the levels of trace
      elements in mussels found in 1982 showed that the trace elemental contamination
      has increased during the last 15 years. From the data obtained, mussel tissue
      appears to be good bio-indicator for identification of coastal areas exposed to
      metallic contaminants.

PMID- 11227553
TI  - Microdetermination of proteins using m-carboxychlorophosphonazo as detection
      probe by enhanced resonance light scattering spectroscopy.
AB  - Proteins can be determined using a common spectrofluorometer to detect the
      intensity of resonance light scattering (RLS). Under acidic conditions, the
      reaction between m-carboxychlorophosphonazo (CPA-mK) and proteins enhances the
      weak light scattering of CPA-mK drastically. This enhanced intensity is
      proportional to the concentration of proteins. The linear ranges for human serum
      albumin are 0.5-35.0 microg/mL, with detection limits of 0.104 microg/mL. The
      method yields results comparable to those of the calorimetric method using
      Coomassie Brilliant Blue G-250 (CBB) with relative standard deviations of 0.72
      2.10% (n = 10). There is almost no interference by amino acids and most of the
      metal ions.

PMID- 11227554
TI  - Voltammetric trace analysis of DNA and RNA.
AB  - A voltammetric determination of DNA/RNA is described. The new aspect is the use
      of the extracellular endonuclease Serratia marcescens in the sample preparation.
      Using this enzyme it is possible to determine DNA/ RNA with a detection limit of
      2-5 pg/mL. This satisfies the requirements of the WHO and the FDA.

PMID- 11227555
TI  - Calibrated nanoinjections of mercury vapor.
AB  - A simple technique for the calibration of mercury vapor chemosensors is
      described. It is based on a reductive deposition of a well-defined quantity of
      mercury (0) onto gold wire followed by thermal evaporation of the mercury into
      the sensor cell. The quantity of mercury on the gold wire was measured
      electrochemically by oxidation before and after heating, as well as after storage
      under different conditions. It is shown that the technique can be used for
      calibrated injections of nanogram quantities of mercury. The approach was applied
      to test the performance of ultrasensitive mercury chemoresistors.

PMID- 11227556
TI  - A new application of humic substances: activation of supports for invertase
      immobilization.
AB  - Invertase was immobilized on aminopropyl silica (APTS-SiO2) activated with humic
      substances (APTS-SiO2-HS) and on aminopropyl silica activated with glutaraldehyde
      (APTS-SiO2-GA). The resulting activity of both systems was compared. Humic
      substances (HS) used for the activation of the silica were extracted from soil of
      Cananeia, Sao Paulo State, Brazil, according to the procedure recommended by the
      International Humic Substances Society. Activity was determined by measuring the
      rate of formation of reduced sugars using the reaction with dinitrosalicylic acid
      (DNS). The amount of HS bound on the APTS-SiO2 was equal to 50 mg. The maximum
      amount of invertase immobilized on APTS-SiO2-HS was 15,200 U/g while in the
      system APTS-SiO2-GA it was 13,400 U/g. The experimental enzymatic activity was
      3,700 and 3,300 U/g, for the systems APTS-SiO2-HS and APTS-SiO2-GA, respectively.
      Considering the increased amount and activity of immobilized enzyme compared with
      the glutaraldehyde method, it was concluded that this technique opens a new
      perspective in the preparation of supports for enzyme immobilization employing
      humic substances.

PMID- 11227557
TI  - Lead in micro-samples of whole blood by Rhenium-cup in-torch vaporization
      inductively coupled plasma-atomic emission spectrometry (ITV-ICP-AES).
AB  - A method is described for screening of lead in diluted micro-samples of whole
      blood by a Re-cup, in-torch vaporization (ITV) sample introduction system for
      inductively coupled plasma-atomic emission spectrometry (ICP-AES). The method
      required minimum sample preparation. For example, blood was diluted with water
      and Triton X-100 in 0.5% HNO3 and, 5 microL were deposited on the Re-cup of the
      ITV sample introduction system. Samples were dried and charred in-situ prior to
      vaporization. Levels 1, 2, 3 and 4 (Pb concentration: 4.04, 10.3, 20.59 and 39.36
      microg/dL) of NIST Standard Reference Material 955b 'lead in bovine blood' were
      used to test accuracy and precision. Accuracy was acceptable and precision was
      below 10% for levels 2-4 and 15% for level 1.

PMID- 11227558
TI  - Reference materials: a gap in the quality system?

PMID- 11227559
TI  - Carbohydrate analysis by high-performance anion-exchange chromatography with
      pulsed amperometric detection: the potential is still growing.
AB  - This article reviews recent advances of carbohydrate analysis by high-performance
      anion-exchange chromatography with pulsed amperometric detection. Starting from
      the paper of Dennis C. Johnson [1] in which the great analytical promise of such
      a technique was anticipated, a multitude of exciting new research possibilities
      have recently emerged. The great attractiveness of high-performance anion
      exchange chromatography is largely due to its compatibility with such a
      sensitive, selective and reliable detection method as pulsed amperometry. This
      very good match between liquid chromatography and electrochemical detection has
      allowed the determination of carbohydrates in a variety of complex matrices, for
      instance, foods, beverages, diary and biotechnological products, vegetal tissues,
      and also in the area of clinical diagnostics. For this reason, the introduction
      of HPAEC-PAD into regulated methods is becoming increasingly accepted. A
      comprehensive collection of applications to carbohydrates and samples of interest
      is given, with special focus on the separation of closely related sugar compounds
      using dilute alkaline eluents. Advances in pulsed potential waveforms are also
      discussed, and a comparison with other liquid chromatographic methods addressed.
      2-keto-3-deoxy-D-glycero-D-galactonononic acid; KDO, 2-keto-3-deoxyoctulosonic
      acid; FOS, fructooligosaccharides; GF5, GF6, and GF7, oligofructans: Hib,
      Haemophilus influenzae type b; FAB, fast atom bombardment; ESI, electrospray
      ionization; MALDI-TOF, matrix assisted laser desorption ionization-time of
      flight.

PMID- 11227560
TI  - Study of the binding characteristics and transportation properties of a 4
      aminopyridine imprinted polymer membrane.
AB  - Molecularly imprinted polymer membranes containing artificial recognition sites
      for 4-aminopyridine have been prepared by photopolymerization using 4
      aminopyridine as template. Reference membranes were prepared with the same
      monomer mixture but in the absence of the template. The binding characteristics
      of the imprinted polymer membrane were investigated by a batch method and the
      transport properties of the membranes were investigated using diffusion chambers.
      The results showed that the binding amount of 4-aminopyridine is higher than that
      of 2-aminopyridine whereas the latter can transport the 4-aminopyridine imprinted
      polymer membrane faster than 4-aminopyridine.

PMID- 11227561
TI  - A polystyrene based membrane electrode for cadmium(II) ions.
AB  - A polystyrene based membrane of 3,4:12,13-dibenzo-2,5,11,14-tetraoxo- 1,6,10,15
      tetraazacyclooctade-cane shows a Nernstian response to Cd(II) ions over a wide
      concentration range (3.16 x 10(-6) - 1.00 x 10(-1) mol L(-1) with a Nernstian
      slope of 29.8 mV/decade of concentration, between pH 2.0 and 6.0. This electrode
      has been found to be chemically inert and of adequate stability with a response
      time of 20s. The electrode gives reproducible results with a lifetime of 130
      days. The membrane works satisfactorily in a partially non-aqueous medium up to a
      maximum 35% (v/v) content of methanol and ethanol. The practical utility of the
      proposed chemical sensor has been observed by using it as end-point indicator in
      the titration of Cd(II) ions with EDTA. The potentiometric selectivity
      coefficient values indicate that the membrane sensor is highly selective for
      Cd(II) ions over a number of cations. Small amounts of surfactants do not disturb
      the functioning of the sensor. This electrode has also been used to estimate
      cadmium ions in real samples.

PMID- 11227562
TI  - Comparison of several spray chambers operating at very low liquid flow rates in
      inductively coupled plasma atomic emission spectrometry.
AB  - Four different spray chambers were evaluated in ICP-AES at very low liquid flow
      rates: a double-pass (Scott type), a conventional cyclonic, and two low-volume
      cyclonic-type spray chambers (i.e., Cinnabar and Genie). A glass concentric
      pneumatic micro nebulizer (Atom Mist) was used in conjunction with all four
      chambers. The liquid flow rate was varied from 10 to 160 microL min(-1). The
      conventional cyclonic spray chamber gave rise to coarser tertiary aerosols,
      higher analyte and solvent transport rates, higher sensitivity and lower limits
      of detection than the remaining ones. The low-volume spray chambers afforded
      analytical figures of merit similar to the double-pass one, despite their very
      different designs. However, these spray chambers exhibited shorter wash-out
      times. The matrix effects were significant only for the double-pass. This fact
      allowed the analysis of reference samples by employing aqueous standards at a
      minimum level of sample consumption. The recoveries obtained for the cyclonic
      spray chambers and several certified samples were close to 100%, being always
      lower in the case of the double-pass spray chamber.

PMID- 11227563
TI  - Application of a modified simplex method to the multivariable optimization of a
      new FIA system for the determination of osmium.
AB  - A methodology based on the coupling of experimental design and a modified simplex
      method is proposed for the optimization of a new flow injection-kinetic system
      for the spectrophotometric determination of Os (IV) with m
      acetylchlorophosphonazo, which has for the first time been used as chromogenic
      reagent in the quantitative analysis of this element. An orthogonal array design
      is utilized to design the experimental protocol, in which six variables are
      varied simultaneously, and obtain the initial simplex using 25 experiments. A
      modified simplex method is applied to continuously optimize the data of the
      orthogonal array design; the search for optimum conditions of 6 variables using
      the modified simplex method required only 25 experiments. The efficiency and
      simplicity of the coupling of the experimental design and the modified simplex
      method are attractive for the development of new analytical methods. The method
      has been applied to the determination of Os (IV) in a refined ore as well as in a
      secondary alloy and provided satisfactory results.

PMID- 11227564
TI  - Determination of the changes of the basic structures of silica species in
      dependence on the concentration of sodium chloride by FAB-MS.
AB  - The chemical species of silica in NaCl solutions of different concentrations were
      identified by FAB-MS (fast atom bombardment mass spectrometry). The basic
      structures of silica species, such as cyclic pentamer (Si5 (OH)9O6-), linear
      pentamer (Sis(OH)11O5-), cyclic hexamer (Si6(OH)9O8-, Si6(OH)11O7-) and linear
      hexamer (Si6(OH)14 O6-), were identified, in addition to dimer (Si2(OH)5O2-),
      trimer (Si3(OH)7O3-) and cyclic tetramer (Si4(OH)7O5-). The patterns of changes
      of the peak intensities of the silicate complexes relative to the dimer with
      increasing NaCl concentration were classified into two types: that represented by
      linear silicate complexes and the other by cyclic silicate complexes. The
      differences in the type of chemical species and their changes according to the
      NaCl concentration reflect the number of bonds necessary for polymerization and
      hydrolysis of the silica complexes. The differences between the linear and the
      cyclic silicate type have some implications on the dissolution mechanism of
      silicate complexes, the hydration of the molecules and the equilibrium between
      solubility, hydrolysis, polymerization and the salting-out effect in NaCl
      solution.

PMID- 11227565
TI  - Polydiphenylamine-dodecyl sulfate films for the simultaneous amperometric
      determination of electroinactive anions and cations in ion-exclusion cation
      exchange chromatography.
AB  - An amperometric detector with two working electrodes both modified with
      polydiphenylamine-dodecyl sulfate (PDPA-DS) was successfully used for the
      simultaneous determination of electroinactive anions (SO42-, Cl-, NO3-) and
      cations (Na+, NH4+ and K+) in single-column ion-exclusion cation-exchange
      chromatography (IEC-CEC). The PDPA-DS chemical modified electrode (CME) was based
      on the incorporation of dodecyl sulfate (DS) into PDPA by electropolymerization
      of diphenylamine in the presence of sodium dodecyl sulfate. The electrochemical
      responses against the anions and cations at the PDPA-DS CME in differential pulse
      voltammetry were studied. A set of well-defined peaks of electroinactive anions
      and cations were obtained. The anions and cations were detected conveniently and
      reproducibly in a linear concentration range 0.01-5.0 mmol/L and their detection
      limits were in the range 5-9 micromol/L at a signal-to-noise ratio of 3 (S/N =
      3). The proposed method was quick, sensitive and simple and was successfully
      applied to the analysis of lake water samples. The working electrode was stable
      over one week period of operation with no evidence of chemical and mechanical
      deterioration.

PMID- 11227566
TI  - Determination of low-level mercury based on a renewable-drops sensing technique.
AB  - The design and characteristics of a novel drop-based fluorescence-detection
      technique for the determination of mercury(II) are described. The method, using a
      flow injection technique, is based on the renewable-drops of 3,3',5,5'
      tetramethylbenzidine(TMB), which are formed at the bottom tip of a silica
      capillary tube connected to the end of the flow system. An excitation beam from a
      high-pressure Hg lamp directly illuminates the drops, the fluorescence emission
      is conducted to a photodiode (PD) to convert the photocurrent into a voltage
      signal (mV). Optimum analytical conditions for Hg(II) assays have been
      established. In NaAc/HAc buffer at pH 3.09 this assay has a wide linear range for
      Hg(II) from 8.0 x 10(-8) to 2.0 x 10(-5) mol/L with a detection limit of 2.0 x
      10(-8) mol/L. The use of renewable drops allowing a fresh reaction surface for
      each sample is of particular value to solving the problems of irreversible
      reactions. Besides its high sensitivity, the method permits a simple, fast, and
      inexpensive measurement with only micro-quantities of reagent consumption. The
      technique described provides a simple and sensitive way to fabricate sensors of
      feasible prospects and commercial advantages.

PMID- 11227567
TI  - Arsenic speciation based on ion exchange high-performance liquid chromatography
      hyphenated with hydride generation atomic fluorescence and on-line UV photo
      oxidation.
AB  - An on-line method capable of the separation of arsenic species was developed for
      the speciation of arsenite As(III), arsenate As(V), monomethylarsenic (MMA) and
      dimethylarsenic acid (DMA) in biological samples. The method is based on the
      combination of high-performance liquid chromatograph (HPLC) for separation, UV
      photo oxidation for sample digestion and hydride generation atomic fluorescence
      spectrometry (HGAFS) for sensitive detection. The best separation results were
      obtained with an anion-exchange AS11 column protected by an AG11 guard column,
      and gradient elution with NaH2PO4 and water as mobile phase. The on-line UV photo
      oxidation with 1.5% K2S2O8 in 0.2 mol L(-1) NaOH in an 8 m PTFE coil for 40 s
      ensures the digestion of organoarsenic compounds. Detection limits for the four
      species were in the range of 0.11-0.15 ng (20 microL injected). Procedures were
      validated by analysis of the certified reference materials GBW09103 freeze-dried
      human urine and the results were in good agreement with the certified values of
      total arsenic concentration. The method has been successfully applied to
      speciation studies of blood arsenic species with no need of sample pretreatment.
      Speciation of arsenic in blood samples collected from two patients after the
      ingestion of realgar-containing drug reveals slight increase of arsenite and DMA,
      resulting from the digestion of realgar.

PMID- 11227568
TI  - Three-phase double-arc plasma for spectrochemical analysis of environmental
      samples.
AB  - A new instrument, which uses a three-phase current to support a double-arc argon
      plasma torch for evaporation, atomization and excitation of solid or powder
      samples, is described. The sampling arc is ignited between the first and second
      electrode while the excitation arc is ignited between the second and third
      electrode. Aerosol generated from the sample (first electrode) is swept by argon
      gas, through a hole in the second electrode (carbon tubing electrode), into the
      excitation plasma. A tangential stream of argon gas is introduced through an
      inlet orifice as a coolant gas for the second electrode. This gas stream forces
      the excitation arc discharge to rotate reproducibly around the electrode surface.
      Discharge rotation increases the stability of the excitation plasma.
      Spectroscopic measurements are made directly in the current-carrying region of
      the excitation arc. An evaluation of each parameter influencing the device
      performance was performed. Analytical calibration curves were obtained for Fe,
      Al, K, and Pb. Finally, the present technique was applied for the analysis of
      environmental samples. The present method appears to have significant, low cost
      analytical utility for environmental measurements.

PMID- 11227569
TI  - A liquid chromatography-tandem mass spectrometry method for fluazifop residue
      analysis in crops.
AB  - An LC-MS-MS assay is described for fluazifop residue analysis in crops. The
      residues are extracted with acidified organic solvent, the esters and conjugates
      are hydrolysed with 6 M hydrochloric acid, then the extracts are cleaned-up by
      solid phase extraction using C2(EC) and Si cartridges in tandem. Quantitative
      analysis is performed by gradient liquid chromatography coupled to triple
      quadrupole mass spectrometer using atmospheric pressure chemical ionisation. All
      fluazifop-P-butyl, free fluazifop-P and any conjugates are quantified as
      fluazifop-P. The limit of quantification is 0.01-0.05 mg/kg depending on crop
      matrices. The clean-up method is also suitable for LC-UV analysis with a
      compromise in higher limit of quantification 0.05-0.2 mg/kg.

PMID- 11227570
TI  - Surface characterization of polydimethylsiloxane treated pharmaceutical glass
      containers by X-ray-excited photo- and Auger electron spectroscopy.
AB  - The siliconization of pharmaceutical glass containers is an industrially
      frequently applied procedure. It is done by spreading an aqueous silicone oil
      emulsion film on the inner surface and successive heat curing treatment at
      temperatures above 300 degrees C for 10-30 min. It was often proposed that a
      covalent bonding of PDMS to the glass or branching of the linear PDMS occurs
      during heat treatment. The present study was performed for a detailed
      investigation of the glass and silicone (polydimethylsiloxane = PDMS) chemical
      state before and after heat-curing treatment and analysis of the bond nature.
      Combined X-ray excited photoelectron (XPS) and Auger electron spectroscopy as
      well as angle resolved XPS-measurements were used for analysis of the glass
      samples. The silicon surface atoms of the borosilicate container glass were
      transformed to a quartz-like compound whereas the former linear PDMS had a
      branched, two-dimensional structure after the heat curing treatment. It was
      concluded that the branching indicates the formation of new siloxane bonds to the
      glass surface via hydroxyl groups. Further evidence for the presence of bonded
      PDMS at the glass surface can be found in the valence band spectra of the
      siliconized and untreated samples. However, this bond could not be detected
      directly due to its very similar nature to the siloxane bonds of the glass matrix
      and the organosilicon backbone of PDMS. Due to the high variation of data from
      the siliconized samples it was concluded, that the silicone film is not
      homogeneous. Previously raised theories of reactions during heat-curing glass
      siliconization are supported by the XPS data of this investigation. Yet, the
      postulation of fixing or baking the silicone on the glass surface is only
      partially true since the bonded layer is very thin and most of the silicone
      originally on the surface after heat curing can be removed by suitable solvents.
      This fraction can therefore still interact with drug products being in contact to
      the siliconized container wall.

PMID- 11227571
TI  - Voltammetric determination of mifepristone at a DNA-modified carbon paste
      electrode.
AB  - A new strategy for the preparation of a DNA-modified carbon paste electrode is
      developed. It is found that the anodic response of mifepristone is greatly
      enhanced at the dsDNA-modified carbon paste electrode comparing with that
      obtained at the bare electrode, while the response at a ssDNA-modified electrode
      is similar to bare electrode. So the dsDNA-modified electrode is employed as a
      sensitive biosensor for the detection of mifepristone. A linear dependence of the
      peak currents on the concentration is observed in the range 2.0 x 10(-7)
      approximately 2.0 x 10(6) mol/L, with a detection limit of 1.0 x 10(-7) mol/L.
      The relative standard deviation is 4.3% for six successive determinations of 1.0
      x 10(6) mol/L mifepristone. The determination of mifepristone tablets is carried
      out and satisfactory results are obtained.

PMID- 11227572
TI  - Determination of vitamin B12 in pharmaceutical preparations by a highly sensitive
      fluorimetric method.
AB  - A fluorimetric method for the determination of vitamin B12 has been developed.
      The fluorescence emission was measured at lambda(ex)/lambda(em)275/305 nm in
      phosphate buffer solution (pH 7.0), and the experimental variables and possible
      interference were studied. The linear calibration range was 1.000 ng/mL to 100.0
      ng/mL with a correlation coefficient of 0.9994 and a detection limit of 0.1
      ng/mL. The method is rapid, simple and highly sensitive. It was used to determine
      vitamin B12 in pharmaceutical preparations. The recovery was 96%-98% and the
      relative standard deviation was in the range of 1.8%-2.7%. The results agreed
      with those obtained by spectrophotometry.

PMID- 11227573
TI  - Quantification of the metal distribution in metallothioneins of the human liver
      by HPLC coupled with ICP-AES.
AB  - Fractions containing metallothioneins (MT's), extracted from the liver cytosol of
      humans, were analysed to determine the complete distribution pattern of the
      metals copper, cadmium and zinc. Samples of cirrhotic livers which had come from
      organs removed during transplantation were examined for differences in the trace
      element binding pattern. After the extraction of supernatants from the tissue
      samples, membrane ultrafiltration of the cytosolic solution was carried out to
      separate all high-molecular proteins with molecular weights >100 kDa. This
      procedure retains the metal content of the MT's in its initial form, in contrast
      to the often-used heat treatment of samples, which changes the copper
      distribution significantly. The MT's themself were isolated using size exclusion
      and anion exchange chromatography. Their metal content was determined
      simultaneously on-line by combination with an ICP-AES as element detector.
      Calibration of the procedure was performed by means of a column by-pass-injection
      of elemental standards into the separation system. The MT content in the samples
      was calculated using the determined metal concentrations and the generally
      accepted metal/protein ratios for Cu (12:1), Cd (7:1) and Zn (7:1). These values
      were compared with values resulting from a 109Cd-saturation-assay. When various
      liver samples of different pathogenesis were compared, the highest level of Cu-MT
      was found in primary biliary cirrhosis.

PMID- 11227574
TI  - Determination of idarubicin in human urine by capillary zone electrophoresis with
      amperometric detection.
AB  - A simple, reliable and reproducible method, based on capillary zone
      electrophoresis with amperometric detection, has been developed for the
      determination of idarubicin in human urine. A carbon disk electrode was used as
      working electrode. The optimal conditions of separation and detection were pH 5.6
      phosphate buffer (0.20 mol/L), 22 kV for the separation voltage and 1.00 V (vs.
      Ag/AgCl, 3 mol/L KCl) for the detection potential. The linear range was from 4.0
      x 10(-7) to 2.0 x 10(-5) mol/L with a regression coefficient of 0.9986, and the
      detection limit was 8.0 x 10(-8) mol/L. The method was directly applied to the
      determination of idarubicin in spiked human urine without any other sample
      pretreatment except filtration, and the assay results were satisfactory.

PMID- 11227575
TI  - Resonance Rayleigh scattering method for the determination of trace amounts of
      cadmium with iodide-basic triphenylmethane dye systems.
AB  - In dilute phosphoric acid solution, cadmium (II) reacts with a large excess of I-
      to form [CdI4]2- which reacts further with basic triphenylmethane dyes such as
      crystal violet (CV), ethyl violet (EV), methyl violet (MV), brilliant green (BG)
      or malachite green (MG) to form an ion-association complex. This results in a
      significant enhancement of resonance Rayleigh scattering (RRS) intensity and the
      appearance of new RRS spectra. The characteristics of RRS spectra of the ion
      association complexes, the influencing factors and the optimum conditions of
      these reactions have been investigated. The intensity of RRS is directly
      proportional to the concentration of cadmium from 0 to 60 ng mL(-1) for EV and MV
      systems, 0 to 80 ng mL(-1) for CV system, and 0 to 100 ng mL(-1) for BG and MG
      systems. The methods exhibit high sensitivities and the detection limits for
      cadmium are between 0.35 and 2.00 ng mL(-1) depending on the different reaction
      systems. The new RRS method was applied to the direct determination of traces of
      cadmium in pure zinc and synthetic water samples.

PMID- 11227576
TI  - Rapid identification of carbendazim and linuron by adsorptive stripping on a
      carbon fiber ultramicroelectrode.
AB  - A method is described for the identification of a mixture of carbendazim and
      linuron. It is based on adsorptive stripping voltammetry at a carbon fiber
      ultramicroelectrode. Conditions for the determination of carbendazim in a mixture
      were optimized and the method was applied to soil samples. It was compared to
      HPLC with spectrophotometric detection, where similar results were obtained.

PMID- 11227577
TI  - Deleting items during instrument development--some caveats.

PMID- 11227578
TI  - Factor replication of the Reduced Laffrey Health Conception Scale.
AB  - This study replicated the factor model for the Reduced Laffrey Health Conception
      Scale (RLHCS), which was originally developed by Laffrey (1986) and reduced by
      Lusk, Kerr, and Baer (1995). Two independent samples of construction workers (n =
      697 and n = 510) were used. The samples were predominately Caucasian males (over
      97%), with mean ages of 35 and 38 years, respectively. Principal components
      factor analysis with direct oblimin rotation and structural equation modeling
      were used to replicate factors and to test the equality of the three observed
      covariance matrices (factory workers and two groups of construction workers),
      respectively. Results replicated the two-factor structure (clinical health and
      overall wellness) found in the earlier study with factory workers (Lusk et al.,
      1995) and demonstrated factor invariance across different samples.

PMID- 11227579
TI  - Development of a Russian satisfaction with Prenatal Care Scale.
AB  - Patient satisfaction with health services is used as a measure of the quality of
      patient care received. The emphasis on accountability and patient as consumer has
      contributed to the growing interest in studying patient satisfaction. Patient
      satisfaction with prenatal care services has not been extensively studied
      including instrumentation to develop a satisfaction scale. The purpose of this
      study was to develop a reliable and valid scale to measure satisfaction with
      prenatal care services in St. Petersburg, Russia, using the 6 satisfaction
      dimensions in Aday and Andersen's Theoretical Framework (1974). It was conducted
      under the auspices of the World Health Organization, Healthy Cities Project.
      Although the study was conducted internationally, it provides a basis for further
      testing of reliability and validity in the United States. A convenience sample of
      397 women with uncomplicated pregnancies and normal deliveries was studied (86%
      response rate). Content, construct, and predictive validity, and reliability
      testing using Cronbach's alpha was conducted. The scale was found to be an
      adequate and theoretically sound measure of satisfaction with prenatal care
      services in Russia. However, rather than the 6 hypothesized satisfaction
      dimensions, Russian women identified 2 satisfaction subscales or measures for
      quality of prenatal care received. One was, as hypothesized, convenience, and the
      other was the doctor's behavior.

PMID- 11227581
TI  - Reliability and validity of the Overeating Tension Scale.
AB  - This study presents the development and testing of the Overeating Tension Scale.
      Overeating tension was defined operationally as the total discrepancy score
      resulting from differences between subjects' ratings of actual and desired
      feelings before overeating. The 32-item Overeating Tension Scale, derived from
      Apter's Reversal Theory, measures reported overall tension and motivation
      specific tension. The scale initially included 48 items, six items for each of
      eight motivational states. After two instrument development studies (N = 373, N =
      208), items were refined and reduced to a total of 32, or four for each of eight
      motivational states. The final version of the instrument was tested in two
      additional studies (N = 330, N = 130) that provided evidence to support the
      internal consistency reliability of the Overeating Tension Scale. There was
      support for construct validity using contrasted groups (overweight and normal
      weight subjects), convergent validity, and factor analysis.

PMID- 11227580
TI  - Measurement of sleep in critically ill patients.
AB  - Research to evaluate interventions to promote sleep in critically ill patients
      has been restricted by the lack of brief, inexpensive outcome measures. This
      article describes the development and testing of an instrument to measure sleep
      in critically ill patients. A convenience sample of 70 alert, oriented,
      critically ill males was studied using polysomnography (PSG), the gold standard
      for sleep measurement, for one night. In the morning the patients completed the
      Richards-Campbell Sleep Questionnaire (RCSQ), a five-item visual analog scale.
      Internal consistency reliability of the RCSQ was .90 and principal components
      factor analysis revealed a single factor (Eigenvalue = 3.61, percent variance =
      72.2). The RCSQ total score accounted for approximately 33% of the variance in
      the PSG indicator sleep efficiency index (p < .001). The data provide support for
      the reliability and validity of the RCSQ.

PMID- 11227582
TI  - An empirical evaluation of an expanded Nursing Stress Scale.
AB  - In the study of work-related stress among nurses, the Nursing Stress Scale (NSS)
      is the best known and most widely used scale. This article presents an overview
      of the NSS and its use, and describes the development of an expanded instrument
      (ENSS) to measure sources and frequency of stress perceived by nurses. Findings
      are based on a random sample of 2,280 nurses in Ontario working in a wide range
      of work settings. Pretests for the study indicated that an expanded version of
      the NSS was necessary in order to adequately measure sources of stress among
      nurses. The sources of stress comprised nine subscales--death and dying, conflict
      with physicians, inadequate preparation, problems with peers, problems with
      supervisors, workload, uncertainty concerning treatment, patients and their
      families, and discrimination. Confirmatory factor analyses, run on two randomly
      selected halves of the sample, came close to meeting standard criteria levels.
      The alpha coefficients of eight of the subscales were .70 or higher, and
      concurrent and construct validity assessments provided strong support for the
      expanded NSS.

PMID- 11227583
TI  - Development and psychometric evaluation of the Caregiver Reciprocity Scale II.
AB  - Caregiver reciprocity is the collective affective and behavioral expression of
      exchanges given and received between a caregiver and care receiver, and among
      family members. This psychometric investigation was designed to further examine
      the reliability and validity of the revised Caregiver Reciprocity Scale II (CRS
      II). Items were rewritten to reflect valued exchanges and balance among the
      entire family network, including spouses. An alpha of .83 for Warmth and Regard;
      .73 for Intrinsic Rewards of Giving; .83 for Love and Affection; and .75 for
      Balance Within Family Caregiving indicated acceptable internal consistency. The
      study, conducted with 176 spouse or adult children caregivers, provides
      additional support for the conceptual model of the four-factor solution.
      Construct validity was supported by the standardized factor loadings and goodness
      of-fit indices obtained from confirmatory factor analysis. The results of the
      analysis of the measurement model, taken as a whole, demonstrate that the CRS II
      has adequate psychometric properties. Model parsimony was supported by an AGFI of
      .87, combined with an adjusted chi-square between 1.0 to 3.0. All but two item
      loadings were greater than .50. This, combined with the fact that all
      standardized loadings were twice the standardized errors and t-values were
      greater than 2.0, contributes to concluding that convergent validity was strong.
      Discriminant validity, evaluated by variance extracted estimates, and confidence
      interval (+/- two standard errors) around the correlation estimate between
      factors, was adequate. This study provided evidence to support the reliability
      and validity of the CRS II.

PMID- 11227584
TI  - Detection of inter-atrial conduction defects with unfiltered signal-averaged P
      wave ECG in patients with lone atrial fibrillation.
AB  - AIMS: To demonstrate a possible inter-atrial conduction delay in patients with
      lone paroxysmal atrial fibrillation (PAF) using 'unfiltered' signal-averaged P
      wave ECG (PSAECG) and compare these results with those obtained with conventional
      filter settings. METHODS AND RESULTS: Twenty one patients with lone PAF and 20
      healthy volunteers (control group) were enrolled in the study. An orthogonal lead
      surface ECG was high-pass filtered at 0.8 Hz, averaged with template matching,
      and combined into a spatial magnitude ('unfiltered' technique). Results were
      compared with conventionally filtered (40-300 Hz) PSAECG. The filtered technique
      revealed no differences in P-wave duration between the two groups (121 +/- 12 vs
      128 +/- 15 ms, control and PAF groups respectively, ns). Double-peaked P-wave
      spatial magnitudes (interpeak distance >30 ms) were revealed in 11 of 21 PAF
      patients but only in two of 18 controls (P<0.01). The nadir in the spatial
      magnitude was located significantly later in the PAF group (114 +/- 13 vs 103 +/-
      9 ms, P<0.01). CONCLUSION: 'Unfiltered' PSAECG revealed significant differences
      in orthogonal P-wave morphology in patients with lone PAF, indicating the
      possibility of an inter-atrial conduction delay, while conventional P-wave
      duration analysis failed to discriminate between the two groups.

PMID- 11227585
TI  - Comparison of spontaneous atrial fibrillation electrogram potentials with the P
      wave electrogram amplitude in dual chamber pacing with unipolar atrial sensing.
AB  - AIMS: Although bipolar sensing is recommended and desirable in patients with dual
      chamber pacemakers (DDD) and intermittent atrial fibrillation (AF) it is a
      clinical reality that some patients who are given unipolar atrial leads without a
      prior history of AF may develop intermittent AF during follow-up. It was
      therefore the purpose of this prospective study to compare the electrogram
      amplitudes of AF potentials with sinus rhythm P-wave potentials as a relevant
      factor for appropriate mode switching in dual chamber pacing with unipolar atrial
      sensing. METHODS AND RESULTS: Forty-two patients with dual chamber pacemakers,
      unipolar atrial leads and intermittent AF were studied. Aside from measuring the
      P-wave potential, it was possible in 14 patients (4 women, 10 men; mean age: 61.8
      (+/- 13.3) years) additionally to document spontaneous AF electrogram potentials
      using pacemaker telemetry. A prospective survey study was performed including a 6
      month follow-up period with an outpatient clinic visit every 2-3 weeks. The mean
      P-wave electrogram amplitude was 3.4 (+/- 1.8) mV (range: 1.4-7.4) compared with
      the mean amplitude during AF of 2.04 (+/- 1.26) mV (range: 0.8-5.2 mV) indicating
      a significant attenuation of 40% during AF (P < 0.0001). A linear correlation
      regression analysis revealed that there was a significant correlation between the
      P-wave and the AF amplitude (P < 0.0001), with a correlation coefficient of r =
      0.867. CONCLUSION: Once it is known that a substantial reduction exists in
      electrogram amplitude, compared with the P wave electrogram potential, an
      estimate can be made of whether AF potentials will be sensed, if the programming
      of atrial sensitivity is congruent with the P-wave characteristics and the
      presence or absence of myopotential triggering.

PMID- 11227586
TI  - Temporary pacing after His bundle ablation for drug-refractory atrial
      fibrillation: a risky enterprise?
AB  - AIM: In patients with and without a permanent pacemaker His bundle ablation was
      performed for symptomatic drug-refractory atrial fibrillation. This study was
      performed to examine the complications of temporary pacing in patients without an
      already implanted pacemaker. METHODS AND RESULTS: Between January 1996 and
      December 1998, 152 consecutive patients, both referred and our own (non
      referred), underwent His bundle ablation for drug-refractory atrial fibrillation.
      Primary end-point complications were temporary lead dislodgement requiring
      immediate repositioning (1), severe arrhythmia (2), death (3) and persistent
      damage to an already implanted pacing system (4). Secondary end-points were
      malsensing and malpacing of the temporary lead, and blood vessel problems. Lead
      dislodgement of the temporary pacemaker occurred in three patients (2.9%), all of
      whom were in the referred group. Severe arrhythmia and death did not occur.
      Persistent damage of the already implanted pacing system was not observed.
      Secondary end-points occurred in 15.8%) of the patients and were successfully
      managed by a conservative approach. CONCLUSION: Permanent pacemaker implantation
      is recommended prior to His bundle ablation in order to avoid haemodynamic
      deterioration due to dislocation of the temporary pacemaker lead. RF current used
      for His bundle ablation caused no permanent damage to permanent pacing systems.

PMID- 11227587
TI  - How to make sure complications are avoided after an otherwise safe procedure.

PMID- 11227588
TI  - How to map and ablate atrial scar macroreentrant tachycardia of the right atrium.
AB  - A special form of macroreentrant atrial tachycardia (MRAT), due to reentrant
      activation around surgical scars, can occur in patients after cardiac surgery.
      Scar MRAT occurs usually after correction of congenital defects, such as atrial
      or ventricular septal defects, and especially after Mustard, Senning or Fontan
      procedures, but it can occur also after myxoma, valvular or coronary bypass
      surgery. The simplest form of scar MRAT is reentry around a lateral right atrial
      surgical scar. A basic mapping array with multiple simultaneous recordings from
      the anterior and septal right atrium is very useful to make the
      electrophysiological diagnosis. A line of double electrograms can be mapped in
      the centre of the circuit and a fragmented electrogram usually marks the pivoting
      point between the inferior end of the scar and the inferior vena cava (IVC).
      Extension of the scar toward the closest fixed obstacle, usually the IVC, by
      means of radiofrequency ablation, can interrupt the tachycardia and make it non
      inducible. Typical atrial flutter usually coexists with scar MRAT and flutter
      isthmus ablation is probably indicated in all cases. In patients having undergone
      baffle atrial surgery it can be impossible to map the whole circuit and
      entrainment-mapping is helpful to localize critical isthmuses in the circuit.
      After the Fontan operation the right atrium can be severely dilated and scarred,
      and multiple, complex reentry circuits can be found. Left atrial MRAT based on
      large areas of scar has been described, but there is still too little experience
      with these to propose general rules for diagnosis and management.

PMID- 11227589
TI  - Temporal and spatial dispersion of repolarization during premature impulse
      propagation in human intact ventricular muscle: comparison between single vs
      double premature stimulation.
AB  - AIMS: This study was performed to determine whether or not the kinetics of action
      potential duration restitution during double premature stimuli (S3) differ from
      that during single premature stimuli (S2) in the human intact right ventricle.
      METHODS AND RESULTS: A monophasic action potential (MAP) was simultaneously
      recorded from the right ventricular apex (RVA) and outflow tract (RVOT) during
      programmed ventricular pacing in 11 patients with symptomatic bradyarrhythmias
      (five males, six females, mean age 58 years). In the five most recent patients,
      the RV pressure and its dp/dt were also obtained during the protocol. A
      substantial difference in the restitution of the MAP duration (MAPD) between S2
      and S3 was observed at short diastolic intervals (< l00 ms), that is, the
      restitution curve of S2 showed an early biphasic pattern (upward hump), while
      such a phenomenon was not seen during the restitution of S3. All the quantitative
      parameters of MAPD restitution representing its kinetics were significantly
      greater in S3 than S2. Maximum attainable dispersion of repolarization between
      the two MAPs was significantly greater during S3 than S2 (76 +/- 17 vs 59 +/- 17
      ms, P<0.05) and was mainly caused by the difference in the MAPD difference, thus
      by the difference in the restitution kinetics of S2 and S3. The dp/dt of the RV
      pressure was significantly greater during S3 than S2 for all diastolic intervals
      tested. CONCLUSION: It was concluded that similar to previously reported canine
      experimental studies, the APD restitution of S3 is substantially different from
      that of S2 in the human intact ventricle (endocardium).

PMID- 11227590
TI  - Effects of intravenous amiodarone on ventricular refractoriness, intraventricular
      conduction, and ventricular tachycardia induction.
AB  - AIMS: Intravenous amiodarone has recently emerged as an important drug for the
      acute treatment of ventricular tachyarrhythmias. However, electrophysiological
      actions and the efficacy of the drug in the suppression of ventricular
      tachycardia inducibility have not yet been fully established. The present study
      was designed to address these issues. METHODS AND RESULTS: The study group
      consisted of 18 patients (all males, mean age 75 +/- 14 years), who underwent
      electrophysiological study due to a history of sustained ventricular
      tachyarrhythmia or syncope with non-sustained ventricular tachycardia detected on
      ambulatory ECG monitoring. The effects of 5 mg.kg(-1) or 10 mg.kg(-1) of
      intravenous amiodarone on (1) ventricular refractoriness (QTc interval, right
      ventricular effective refractory period and monophasic action potential
      duration), (2) intraventricular conduction (paced-QRS and signal-averaged QRS
      duration), and (3) ventricular tachycardia inducibility, were examined. The drug
      had no significant effect on ventricular refractoriness. However, a relatively
      small but significant slowing of intraventricular conduction was seen (paced-QRS
      duration: 182 +/- 27 ms vs 191 +/- 28 ms, P<0.0007; 183 +/- 32 ms vs 195 +/- 33
      ms, P<0.0007; and 177 +/- 21 ms vs 192 +/- 24 ms, P<0.003, at the cycle lengths
      of 600, 500 and 400 ms, respectively). This effect was more evident during
      extrasystolic beats than during stable pacing (for example, at the cycle length
      of 600 ms, the magnitude of amiodarone-induced lengthening of QRS duration was
      23.9 +/- 17.6 ms vs 9.7 +/- 7.2 ms, P<0.009, respectively). Intravenous
      amiodarone did not prevent induction of sustained ventricular tachycardia in any
      of five patients inducible at baseline. Of six patients with non-sustained
      ventricular tachycardia, five had sustained ventricular tachycardia or
      fibrillation induced after amiodarone infusion. CONCLUSION: Intravenous
      amiodarone does not prolong ventricular refractoriness, slows intraventricular
      conduction and may facilitate inducibility of sustained ventricular arrhythmias.

PMID- 11227591
TI  - Arrhythmogenic mechanisms in left ventricular hypertrophy.
AB  - An important mechanism contributing to the high mortality and sudden death in
      patients with left ventricular hypertrophy (LVH) is ventricular arrhythmia. Part
      of the risk is associated with the pro-arrhythmic electrophysiological phenotype
      of the hypertrophied myocardium. The most consistently observed abnormality is
      prolongation of the action potential duration and refractoriness, which sets the
      stage for arrhythmias based on early or delayed afterdepolarizations and
      triggered activity. In addition, non-uniform prolongation of the action potential
      in LVH may be pro-arrhythmic by leading to increased dispersion of repolarization
      or refractoriness and favouring re-entry. The occurrence of delayed after
      depolarization-induced triggered activity and other ventricular arrhythmias are
      also related to the impaired ability to handle intracellular calcium due to
      changes in the density of ryanodine receptors and the Ca2+-ATPase of the
      sarcoplasmic reticulum. Slowing and fractionation of ventricular conduction,
      creating the conditions for micro-reentry and arrhythmogenesis, are
      characteristic of severe LVH, as is the expression of the I(f) current (which may
      be a source of increased automaticity). The pro-arrhythmic potential of LVH is
      also related to the presence of coexisting 'extrinsic' factors. The most
      important and pro-arrhythmic association of LVH is that with myocardial
      ischaemia. Other conditions include neuroendocrine factors, ventricular wall
      stress or electrolyte disturbances. The electrophysiological mechanisms of the
      interactions between these 'extrinsic' factors and LVH have not been fully
      elucidated. Further research into these mechanisms is required and may have
      important implications for our understanding of the mechanisms of cardiac
      arrhythmias in LVH and the appropriate use of antiarrhythmic drug therapy.

PMID- 11227592
TI  - Sudden death in a child with an unusual accessory connection.
AB  - An 8-year-old boy with Wolff-Parkinson-White syndrome died suddenly whilst
      exercising. He had been well with no immediate preceding symptoms of an
      arrhythmia, and was receiving no drugs. As an infant he had suffered recurrent
      episodes of atrioventricular reciprocating tachycardia (AVRT) and had documented
      pre-excited atrial fibrillation. At electrophysiological (EP) study, the
      refractory periods of his two accessory pathways were less than 220 ms. Drugs
      were discontinued at 4 years of age when he remained asymptomatic. Autopsy
      confirmed a very unusual accessory pathway. It was a muscular connection between
      the base of the right atrial appendage and the right ventricle, distant from the
      annulus of the tricuspid valve.

PMID- 11227593
TI  - A comparison between passive and active fixation leads in the coronary sinus for
      biatrial pacing: initial experience.
AB  - AIMS: It has been reported that biatrial pacing can prevent the recurrence of
      atrial fibrillation. This technique requires a stable coronary sinus (CS) lead
      position for left atrial pacing. We report our experience of CS pacing with a
      specifically designed lead [Medtronic 2188 (n= 19)] and active fixation leads
      [Pacesetter Tendril (n=3), Medtronic Capsurefix (n=6)] in 21 patients with
      paroxysmal atrial fibrillation and a normal mean left atrial size of 39 mm (range
      33-54 mm). METHODS AND RESULTS: Using the Medtronic 2188 lead, successful initial
      CS canulation and lead positioning was achieved in all 19 patients. One patient
      developed subclavian vein thrombosis 3 months after initial implant. Eight
      patients (42%) experienced subsequent lead displacement (12 displacements in
      total). Of these, seven had their lead replaced with active fixation leads. In
      addition, two patients underwent active fixation lead implantation at first
      implant. CS canulation and lead positioning was successful in all nine patients.
      No patient suffered displacement of an active fixation lead. There were no
      complications in this group. Twelve of the 19 (66%) Medtronic 2188 leads were
      functioning at long-term follow-up (11 +/- 4 months) with a biatrial pacing
      threshold of 2.4 +/- 1 V. Eight of the nine (89%) active fixation leads were
      functioning at long-term follow-up (6 +/- 3 months) with a biatrial pacing
      threshold of 2.9 +/- 1.1 V. Using a combined approach 95% of patients had a
      functioning CS lead at long-term follow-up. CONCLUSION: Active fixation leads can
      safely be used for left atrial pacing via the CS with good long-term pacing
      thresholds and stability.

PMID- 11227594
TI  - Initial United Kingdom experience with the use of permanent, biventricular
      pacemakers: implantation procedure and technical considerations.
AB  - AIMS: To describe the institution of a biventricular pacing programme with
      particular reference to the implantation procedure and new technological
      considerations. METHODS AND RESULTS: Analysis of outcomes of a consecutive series
      of 54 patients undergoing attempted biventricular pacemaker implantation between
      February 1998 and April 1999. Successful implantation was achieved in 49 of the
      54 patients (91%). Five patients required lead repositioning after initial
      successful implantation. Left ventricular lead pacing thresholds were found to be
      satisfactory and stable in the long term, with pacing thresholds of 1.3 V, 1.9 V
      and 1.6 V at implantation, 1 and 3 months, respectively. Left-sided lead function
      was not dependent on lead position within the tributaries of the coronary sinus.
      The implantation procedure was found to be safe, although one patient died during
      long-term follow-up. CONCLUSION: With appropriate previous experience in complex
      and coronary sinus pacing and with access to up-to-date pacemaker and lead
      technology, a biventricular pacemaker implantation service can be instituted with
      good medium-term results.

PMID- 11227595
TI  - Latest generation of unipolar and bipolar steroid eluting leads: long-term
      comparison of electrical performance in atrium and ventricles.
AB  - One hundred and seventy-three patients, mean age 74 years permanently paced with
      123 atrial (53 unipolar, 70 bipolar) and 143 ventricular (73 unipolar, 70
      bipolar) pacing leads were included in this study. The pacing leads were recent
      generation low surface area steroid eluting leads from one manufacturer: leads
      with silicone and polyurethane insulation were studied, and they were combined
      with generations of one pacemaker family from the same manufacturer permitting
      identical measurements to be made over a follow-up of 2 years. Pacing threshold
      was measured using pulse duration at a fixed voltage of 1.5 V: peak to peak P and
      R wave amplitude and pacing impedance at 2.5 V and 0.5 ms were all measured using
      the manufacturer's standard programmer. Although many significant differences, in
      the parameters measures, existed between atrium and ventricle and unipolar and
      bipolar configurations, none was felt to be of clinical significance. These data
      permit the physician to choose the lead type with regard to sensing performance
      and long-term lead integrity.

PMID- 11227596
TI  - Clinical experience of a new rate drop response algorithm in the treatment of
      vasovagal and carotid sinus syncope.
AB  - Dual chamber pacing has proven beneficial in patients with sudden drops in heart
      rate as seen in vasovagal syncope and carotid sinus syndrome. Newer algorithms
      for faster detection of an insidious drop in heart rate and short lasting
      intervention pacing at a high rate, as in the rate drop response algorithm in the
      Medtronic Kappa series of pacemakers, might improve the effect of pacing. Two
      case reports, that demonstrate the use of these rate drop response algorithms,
      are presented. A 24-year-old woman with recurrent episodes of syncope and
      repeated tilt-table tests with vasovagal cardioinhibitory outcomes had a
      Medtronic Kappa 400 pacemaker implanted. Syncope was abolished during repeat tilt
      table testing following pacemaker implantation and proper functioning of the rate
      drop response algorithm. The patient has been free of syncope during follow-up
      apart from a single episode that occurred due to neglect of vasovagal warning
      symptoms. A 52-year-old man with coronary artery disease developed recurrent
      blackouts. Carotid sinus massage resulted in 5.5 s of asystole and presyncope. A
      Medtronic Kappa 700 pacemaker with a rate drop response algorithm was implanted
      and the patient became asymptomatic. The rate drop response algorithm is
      discussed in detail based upon the case reports, and recommendations are given
      for the use of this algorithm in patients with vasovagal syncope and carotid
      sinus syndrome.

PMID- 11227597
TI  - The registry of the European Working Group on Cardiac Pacing (EWGCP). A working
      group of the European Society of Cardiology.

PMID- 11227598
TI  - Diagnostic assessment of recurrent unexplained syncope with a new subcutaneously
      implantable loop recorder. Reveal-Investigators.
AB  - AIM: Patients with recurrent syncope undiagnosed after extensive non-invasive and
      invasive testing pose a diagnostic and therapeutic dilemma. Holter monitoring is
      nondiagnostic in 90% of cases. Recent developments in loop recorder technology
      permit long-term ECG monitoring in patients with recurrent unexplained syncope.
      The aim of this study was to report the worldwide experience with a new
      subcutaneously implantable loop recorder, implanted in 133 patients with
      unexplained syncope and negative laboratory investigations. METHODS AND RESULTS:
      The implantable loop recorder monitors continuously a single lead electrogram
      using two sensing electrodes on the device shell. The device was implanted in 133
      patients, 67 male and 66 female with recurrent syncope. During a mean follow-up
      of 10.8 +/- 4.3 months after device implantation, 83 patients (62%) experienced
      syncope or pre-syncope. In the remaining 50 patients no diagnosis could be made
      because either no events occurred, the patients were lost to follow-up, had
      adverse events, or died prior to diagnosis. In 72 of the 83 patients with syncope
      during follow-up (87%), loop recording definitively determined whether an
      arrhythmia was the cause of symptoms or not. Diagnosis included bradycardia in 21
      patients, pacemaker dysfunction in one patient, and tachycardia in 10 patients.
      One patient experienced multiple rhythm disturbances. Syncope was non-arrhythmic
      in 40 patients. The remaining 11 patients failed to press the activator. Therapy
      was instituted in all patients, in whom an arrhythmic cause was found. Severe
      anticipated device related complications occurred in three patients. CONCLUSION:
      An implantable loop recorder is useful for establishing a diagnosis when symptoms
      are recurrent but too infrequent for conventional monitoring techniques.

PMID- 11227600
TI  - The road ahead.

PMID- 11227599
TI  - Is electrical storm in ICD patients the sign of a dying heart? Outcome of
      patients with clusters of ventricular tachyarrhythmias.
AB  - BACKGROUND: Electrical storm in patients with implanted cardioverter
      defibrillators (ICDs) is purported to carry an ominous prognosis. METHODS AND
      RESULTS: We retrospectively compared 40 patients with electrical storm (defined
      as three or more episodes of ventricular arrhythmia requiring ICD therapy in a 24
      h period) with those only having isolated appropriate ICD therapy (n=57) and with
      patients having no or only inappropriate ICD therapy (n=125). All patients
      received ICDs for documented sustained VT or VF. There was no significant
      difference in age, sex, ejection fraction, total follow-up time, or underlying
      heart disease between any of the three groups. Patients who had electrical storm
      received their first appropriate ICD therapy 275 +/- 369 days post-implant (35%
      had storm as their first event) with storm occurring an average of 599 +/- 710
      days post-implant. Patients had 1.5 +/- 1.0 storms in total (median= 1), with 55
      +/- 91 episodes per storm. There were no significant differences in actuarial
      survival at 5-year follow-up between the three groups. Eighty percent of storm
      patients were alive 5 years post-implant. CONCLUSION: Storm is a common
      occurrence in ICD patients, can occur at any time during the follow-up period,
      and does not independently confer increased mortality.

PMID- 11227601
TI  - The role of public health in disaster preparedness, mitigation, response, and
      recovery.

PMID- 11227602
TI  - The public health consequences of disasters.
AB  - Although disasters have exacted a heavy toll of death and suffering, the future
      seems more frightening. Good disaster management must link data collection and
      analysis to the decision-making process. The overall objectives of disaster
      management from the viewpoint of public health are: 1) needs assessments; 2)
      matching available resources with defined needs; 3) prevention of further adverse
      health effects; 4) implementation of disease-control strategies; 5) evaluation of
      the effectiveness of the application of these strategies; and 6) improvement in
      contingency planning for future disasters. The effects of sudden-onset, natural
      disasters on humans are quantifiable. Knowledge of the epidemiology of deaths,
      injuries, and illnesses is essential to determine effective responses; provide
      public education; establish priorities, planning, and training. In addition, the
      temporal patterns for the medical care required must be established so that the
      needs in future disasters can be anticipated. This article discusses: 1) the
      nature of disasters due to sudden-onset, natural events; 2) the medical and
      health needs associated with such events and disasters; 3) practical issues of
      disaster responses; and 4) the advance organization and management of disasters.
      The discussion also includes: 1) discussions of past problems in disaster
      management including non-congruence between available supplies and the actual
      needs of the affected population; 2) information management; 3) needs
      assessments; 4) public health surveillance; and 5) linking information with
      decision-making. This discussion is followed by an analysis of what currently is
      known about the health-care needs during some specific types of sudden-onset,
      natural disasters: 1) floods; 2) tropical cyclones; 3) tornadoes; 4) volcanic
      eruptions; and 5) earthquakes. The article concludes with descriptions of some
      specific public-health problems associated with disasters including epidemics and
      disposition of corpses. All natural disasters are unique in that the regions
      affected have different social, economic, and health backgrounds. But, many
      similarities exist, and knowledge about these can ensure that the health and
      emergency medical relief and limited resources are well-managed.

PMID- 11227603
TI  - Disaster public health considerations.
AB  - This paper provides an overview of disaster public health preparedness, response,
      and recovery activities with particular reference to examples that have occurred
      in California. It discusses the public health considerations from two aspects: 1)
      general public health effects; and 2) public and environmental health control
      measures. The latter discussion is divided into: 1) drinking water; 2) human
      wastes; 3) food; 4) personal hygiene; 5) mass care and shelter; 6) solid waste
      and debris; 7) hazardous materials; 8) injury prevention programs and public
      health information; 9) vector control; and 10) disease control and surveillance.
      Two tables summarize the disaster medical and health functions as they relate to
      public health.

PMID- 11227604
TI  - Public health assessments in disaster settings: recommendations for a
      multidisciplinary approach.
AB  - INTRODUCTION: Rapid assessments of needs and health status have been conducted by
      the U.S. Centers for Disease Control and Prevention (CDC) in natural disaster
      settings for gathering information about the status of affected populations
      during emergencies. A review of eight such assessments (6 from hurricanes, 1 from
      an ice storm, and 1 from an earthquake) examines current methods and
      applications, and describes the use of results by policy makers so assessments in
      post-disaster settings can be improved. OBJECTIVE: Because the results of
      assessments greatly influence the nature of relief activities, a review can: 1)
      ascertain strengths and limitations; 2) examine the methods; and 3) ascertain the
      utility of results and their use by policy makers. This review compares
      assessments for similarities and differences: 1) across disaster types; 2) within
      similar disasters; 3) by timing when the assessments are conducted; and 4) in
      domestic and international settings. The review also identifies decision-making
      actions that result from the assessments, and suggests direction for future
      applications. METHODS: Assessments reported in CDC's Morbidity and Mortality
      Weekly Report from 1980 through 1999 were reviewed because they applied a
      systematic methodology in data collection. They were compared descriptively for
      study characteristics and content areas. RESULTS: Of 13 assessments identified
      from six reports, eight were reviewed because they focused on initial
      assessments, rather than on repeated studies. Of the eight, six pertained to
      hurricanes; one to an ice storm; and one to an earthquake. Seven (88%) were
      performed during or after the third day post-impact (range: 1-70 days, median: 7
      days). All eight addressed demographics, morbidity, and water availability; seven
      concerned food, sanitation, and transportation; and six queried access to medical
      care and electricity. Of the three assessments conducted more than 10 days post
      event, two addressed vulnerable children, the elderly, pregnant and lactating
      women, and migrant workers; two singled storm preparation and evacuation
      behavior; and one concerned mental health, preventive health care, and social
      programs. Only one, after an earthquake, asked about disaster-related deaths in
      household members. Two were international assessments and both were performed at
      least 60 days post-event. All eight provided estimates of proportions of needs
      based on survey respondents; none, however, extrapolated the proportions to
      estimate the magnitude of needs for populations at risk. Of the eight, five
      confirmed a policy decision, such as accelerating delivery of food supplies.
      CONCLUSION: Assessments typically were conducted within 1 week after the
      precipitating event occurred. Most, performed within 3-10 days, focused on
      demographics, health status, food and water, and restoration of utilities. Three
      assessments, conducted > 1 month later, concerned long-term planning. Only one
      was performed < 72 hours post-event. Five assessments resulted in policy actions
      to guide relief activities. Increasing application of health assessments
      provides: 1) impetus for improving current methodologies; 2) standardizing
      collection instruments; 3) involving other sectors in emergency relief; and 4)
      ensuring useful information for decision makers.

PMID- 11227605
TI  - Impact of the 1994 Northridge earthquake on the utilization and difficulties
      associated with prescription medications and health aids.
AB  - INTRODUCTION: The medical impacts of disasters have focused on the injuries,
      illnesses, and deaths related to the disaster. Little has been written about the
      impact of disasters on persons who use prescription medications or those
      medications that require refrigeration, or those who require health aids. The
      objective of this study was an evaluation of the level of utilization of
      prescription medications and medications that require refrigeration as well as
      the use of health aids by the population affected by the disaster. METHODS:
      Following the Northridge earthquake of 1994, a survey of Los Angeles County
      households was conducted to assess the impact of the earthquake. A total of 1247
      households completed the 48 minute telephone interview. As part of the interview,
      10 questions assessed the utilization of medications and medical aids by
      household members and the effects that the earthquake had on those medications
      and devices. Chi-square, analysis of variance (ANOVA), and logistic regression
      analysis were applied. RESULTS: Of the 1,212 completed interviews, 21% of the
      households had a family member taking a prescription medication or a medication
      requiring refrigeration. Associated factors included gender, race, age, household
      income, level of education, presence of children, and the intensity of the
      earthquake (by the Modified Mercalli Index). Only 3% of those that reported
      medication usage noted problems associated with the use of these medications.
      Thirty-nine percent of the respondents indicated that someone in the household
      used a health aid (e.g., eyeglasses, hearing aid, etc.). Usage was related to
      gender, race, age, household income, level of education, presence of children,
      and the intensity of the shaking associated with the earthquake. Of these, 6.5%
      reported difficulty with these aids, usually related to loss or breakage.
      CONCLUSIONS: Although the proportions of the population requiring prescription or
      refrigerated medications and/or for those using health aids in Los Angeles
      seemingly are small, this translates to 630,000 households in which someone
      requires medications and 1.2 million households with a requirement for health
      aids. Thus, there are a huge number of persons at risk for serious medical
      problems related to these medications and devices that could produce profound
      medical problems during a disaster. However, during and following a moderate
      earthquake, it does not seem that the consequences will be great.

PMID- 11227606
TI  - Controversy and consensus in disaster mental health research.
AB  - Controversies regarding the mental health consequences of disasters are rooted
      both in disciplinary orientations and in the widely varied research strategies
      that have been employed in disaster mental health studies. However, despite a
      history of dissensus, there are also key issues on which researchers agree.
      Disasters constitute stressful and traumatic experiences. However, vulnerability
      to such experiences, as well as to more chronic stressors, is socially
      structured, reflecting the influence of socio-economic status and other axes of
      stratification, including gender, race, and ethnicity. Disaster events differ in
      the extent to which they generate stress for victims. A holistic perspective on
      disaster mental health would take into account not only disaster event
      characteristics, but also social-systemic sources of both acute and chronic
      stress, secondary and cumulative stressors, and victims internal and external
      coping capacities.

PMID- 11227607
TI  - Ally or adversary? Using media systems for public health.
AB  - The media system controls information resources that public health agencies may
      wish to use to accomplish their goals, particularly in a crisis. The resources of
      the public health system sometimes are prized by the media system, and this
      provides opportunities for public health agencies to gain access to the media.
      This paper reviews the goals and resources of the media system as they relate to
      the mission of public health agencies in the periods before, during, and after a
      public health crisis. The various media are reviewed with attention to the role
      each can play for different purposes and at different stages of a crisis. The
      importance of presenting health information in the form of stories is emphasized,
      with specific advice regarding the attributes of an effective story.

PMID- 11227609
TI  - Non-institutional sources of assistance following a disaster: potential triage
      and treatment capabilities of neighborhood-based preparedness organizations.
AB  - The following paper presents an argument for enhancing and encouraging the
      development of neighborhood-based disaster preparedness organizations,
      particularly as a potential medical triage and treatment resource following a
      disaster. First, the research context for the utility of non-institutional
      sources of post-diaster assistance is outlined, followed by the more specific
      instance of medical triage and treatment. An emerging model of community disaster
      preparedness training is described, noting the modules that address disaster
      medicine. Positive contributions and limitations are addressed looking to
      disaster and non-disaster experiences. While the potential for non-traditional
      resources to aid immediate post-disaster response is becoming both more common
      and more accepted, there are a number of recommendations that would improve the
      usefulness and value, including: 1) integration with existing emergency care
      infrastructure; 2) standardization of training; 3) use of coordinated drills
      between public safety organizations, hospitals, and voluntary sectors; and 4)
      dedication of more funding to assist in the creation and maintenance of programs.
      Because of the relative infancy of these community-based programs, and the
      infrequency of large-scale disasters, there is little, if any, pre-post research
      that can demonstrate a measured impact on response. More pre-disaster baseline
      data-gathering efforts are needed, combined with post-disaster evaluative
      research to understand the utility of these non-traditional resources in terms of
      overall response, and in particular the ability to assist in areas of disaster
      medicine practice. One also expects that under these kinds of [disaster]
      conditions, family members, fellow employees, and neighbors will spontaneously
      try to help each other. This was the case following the Mexico City earthquake
      where untrained, spontaneous volunteers saved 800 people. However, 100 people
      lost their lives while attempting to save others. This is a high price to pay and
      is preventable through training.

PMID- 11227608
TI  - How to talk to the media: televised coverage of public health issues in a
      disaster.
AB  - Public health officials often are critical of the way television news covers
      disasters, while broadcast journalists complain of a lack of cooperation from the
      public health sector during disaster coverage. This article summarizes the issues
      discussed in a session on Televised Coverage of Disasters, presented in April
      1999 at the UCLA Conference on Public Health and Disasters in Los Angeles. Public
      health officials were asked to "talk back to their television sets" in a dialog
      with television journalists. Concerns included: 1) the lack of balance in
      television coverage that is dominated by sensational images that may frighten
      rather than inform the public; 2) the potential for psychological damage to
      viewers when frightening images are shown repeatedly in the days and weeks of the
      disaster; and 3) the perception that TV reporters place too much emphasis on
      crime, property damage, and loss of life, giving relatively low priority to
      disaster preparedness and to public health issues in the aftermath of a disaster.
      Options for improving communication between television journalists and public
      health professionals also are discussed.

PMID- 11227610
TI  - Community collaboration in disaster: the role of voluntary agencies.
AB  - Although the United States has been impacted by numerous devastating disasters
      over the last 10 years, there have been only limited efforts between the
      governmental and non-profit/voluntary organizations to meet the multiple disaster
      health and mental health needs of the community. Too often, responding
      organizations compete to provide services, duplicate efforts, and frequently
      under-estimate the need for services. Recent efforts have been undertaken by The
      American Red Cross and other groups to resolve this issue. Governmental and
      community-based organizations have been invited to participate in planning
      sessions to pre-identify roles and responsibilities, as well as to exchange key
      information about the services each group can and does provide. These efforts
      have lead to an increased awareness of the potential problems and the development
      of cohesive plans to provide medical and emotional support services to impacted
      communities. This has led to improved care for those with serious injuries or
      psychological crisis, while those with less critical problems have been managed
      appropriately without needing to be immediately referred to overcrowded emergency
      departments or physician's offices.

PMID- 11227611
TI  - Lessons learned in public health emergency management: personal reflections.
AB  - Multiple environmental, ecological, and socio-political forces are converging to
      increase the occurrence of both natural and technological disasters. Ten forces
      are of most concern in this regard. These are: 1) global warming, with its
      consequent weather extremes and climate changes; 2) continued rapid human
      population growth and concomitant increased urbanization; 3) decreased bio
      diversity and consequent ecological fragility; 4) deforestation and loss of
      natural habitat for animal species, with resultant greater overlap of human and
      animal habitats, human exposure to animal pathogens, and other ecological
      perturbations; 5) increased technological development throughout the world
      (especially in developing countries with their typically immature safety
      programs); 6) globalization and increased population mobility; 7) sub-national
      religious and ethnic conflicts, and their potential for conflict escalation and
      large scale displacement of populations; 8) the collapse of several major
      countries and consequent unraveling of national identity and social order; 9) the
      rise of terrorism; and 10) dramatic advances in the science and technology of
      computing, communications, biotechnology, and genomics. This paper describes 10
      lessons learned relative to the public health aspects of emergency management,
      especially as they pertain to disasters. 1) Planning pays; 2) A bad situation can
      be made worse by inappropriate responses; 3) Most life saving interventions will
      occur before the disaster happens and immediately afterwards by local action; 4)
      Public health emergency management is not a democratic process; 5) Psychological
      impacts are usually greater than anticipated; 6) Communications and information
      management are vital, but often are the weak link in the response chain; 7)
      Collaboration and partnerships are essential; 8) Unsolicited volunteers and aid
      are inevitable and must be planned for and managed; 9) Never assume anything, and
      always expect the unexpected; and 10) Post-event evaluation is important, and
      must be coordinated. The paramount lesson learned from past emergencies is that
      the untoward impact of these events can be anticipated and significantly
      ameliorated by appropriate planning and preparation. On the other hand,
      preparation for emergency events has deteriorated because of health-care
      financial constraints, and resources to support planning and needed
      infrastructure have diminished. Given these realities, the major unresolved
      challenge is how to ensure that planning for the common good is supported and, in
      fact, gets done.

PMID- 11227612
TI  - Fred C. Cuny Memorial Continuing Education Series. Lesson 10: group dynamics in
      disasters: managing work groups.
AB  - Groups are assigned or formed to perform tasks that one person cannot accomplish
      alone. This lesson describes the classification of work groups, group unity,
      leadership, motivation, recognition, conflict resolution, and remediation
      associated with managing groups and their activities. Advantages associated with
      group process include 1) the generation of better ideas, 2) ability to assume
      greater risks; make fewer errors; 3) the capacity for greater knowledge and 4)
      information, and for some problems, production of better decisions. Groups may be
      formal or informal. Formal groups may be organic, task-directed, or committees.
      Informal groups arise when it becomes obvious that a group will work better or
      may be formed by a discipline within the organization or through friendships. The
      size of the group its status within the organization, the goals established, and
      the dependence of the members on the group all may affect the cohesiveness of the
      group. Leadership of the group must keep the group focused on the objectives and
      enhancement of the efficiency of its operation and the quality of the decisions
      made by the group. Motivation of a group often is more difficult than is that for
      individuals and generally positive inducements work better than do negative
      measures such as coercion and reprimands. Roles are often informal and conferred
      by the group collectively. Often norms are established within groups that help
      the group deal with conflict. Inadequate performance within a formal group may
      require changes in the leadership, removal of a member or clique within the
      group, reduction of group size, and/or dissolution of the group. Understanding
      the dynamics of groups is an essential skill required of good managers.

PMID- 11227613
TI  - Antibacterial effect of some leaf extracts on Salmonella typhi.
AB  - Aqueous and methanol extracts of fresh leaves of twenty desert plants of
      Rajasthan state were tested for their antibacterial activity against human
      pathogenic bacteria Salmonella typhi, causal organism of typhoid fever in human
      beings. 10% concentrate extracts of leaves of various plant species were used for
      testing antibacterial potential. Five plant species were found to have inhibitory
      effect against the organism. Fagonia cretica leaf extracts were found most
      effective against Salmonella typhi.

PMID- 11227614
TI  - Hair loss.

PMID- 11227615
TI  - ACE inhibitor reduces cardiovascular events by 22%.

PMID- 11227616
TI  - Interrelationship between angiographically defined coronary artery disease,
      plasma insulin levels and lipids in Indian patients.
AB  - We investigated the interrelationship between plasma insulin levels, various
      lipoproteins and coronary artery disease. No significant differences were
      observed on comparing patients with controls for plasma insulin, high density
      lipoprotein cholesterol, fasting blood sugar levels and triglyceride levels.
      However patients showed significantly higher levels of total cholesterol and low
      density lipoprotein cholesterol compared with controls. No significant
      differences were observed on comparing patients of multivessel disease with
      single vessel disease in serum insulin or various lipid subfractions. In
      addition, there was no correlation between serum insulin quartiles and various
      biochemical parameters. In conclusion, in this cross-sectional study plasma
      insulin levels failed to show any significant association with severity and
      extent of coronary artery disease. Further there was no correlation of various
      lipid parameters with insulin quartiles.

PMID- 11227617
TI  - Prevalence of nonfermenters in clinical specimens.
AB  - One hundred and thirty three non fermenting gram negative bacilli isolated out of
      625 different clinical specimens were identified and characterised. Samples were
      exudate from chronic suppractive otits media (341), diabetic foot (117) wound
      (116) and blood (51). Of these isolates Pseudomonas aeruginosa 105(78.94%)
      predominated followed by Acinetobacter sp 8 [6.1%], Pseudomonas putrifaciens
      6(4.5%), Flavobacterium sp 6(4.5%), Xanthomonas maltophilia 5(3.75%), Alkaligenes
      sp 3 (2.25). 31 (23.30%) were resistant to commonly used antibiotics. Amikacin 85
      (63.90%) was found to be more effective than fluoroquinolones (27.8-48.12%).

PMID- 11227618
TI  - Adenosine deaminase in cord blood as an immunoenzyme marker in low birth weight
      neonates.
AB  - Adenosine Deaminase (ADA) levels were estimated in cord blood of 30 neonates born
      with birth weight less than or equal to 2.5 kg and 30 neonates born with birth
      weight greater than 2.5 kg. The mean ADA levels in low birth weight (LBW) group
      was found to be 6.94 U/L and in normal birth weight group the mean ADA levels
      were 14.37 U/L which was statistically significant. Therefore ADA may be useful
      in assessing CMI status in low birth weight infants.

PMID- 11227619
TI  - Mesenteric panniculitis presenting as a huge retroperitoneal mass--a case report.
AB  - A rare case of mesenteric panniculitis occurring in a young patient and
      presenting as a huge retroperitoneal mass which was mistaken for malignancy, has
      been described.

PMID- 11227620
TI  - Primitive society, health & elderly.
AB  - Mankind have been ravaged by diseases since primitive age and remedial measures
      were emprirical learnt either by accident, experience or superstition. But most
      elderly population were killed and hardly died of diseases. Fate of women were no
      better. Care for elderly came with civilization. They were little better in the
      East compared to the West. Although elderly population were better treated in
      India, China tops the list for elderly care. Even today the oldest man in the
      family is most respected. Civilized nations even today discriminate elderly
      population compared to children and adult, but apply the yardstick in a different
      manner, direct killing alone is not allowed.

PMID- 11227621
TI  - Drug therapy for methicillin-resistant Staphylococcus aureus.

PMID- 11227622
TI  - Catastrophic antiphospholipid antibody syndrome.
AB  - The antiphospholipid antibody syndrome may be associated with connective tissue
      disorders. We describe a patient with catastrophic antiphospholipid antibody
      syndrome secondary to systemic lupus erythematosus who presented with recurrent
      abdominal symptoms. Our patient died, and autopsy revealed hemorrhagic infarction
      of bowel with numerous mesenteric hemorrhages. The treatment for antiphospholipid
      antibody syndrome ranges from aspirin, warfarin, and plasmapheresis to prednisone
      and hydroxychloroquine.

PMID- 11227623
TI  - The value of a well-designed tumor board.

PMID- 11227624
TI  - Culturing the throat to protect the heart.

PMID- 11227625
TI  - Fool's gold: legalized gambling.

PMID- 11227626
TI  - Borderline intellectual functioning in children and adolescents: reexamining an
      underrecognized yet prevalent clinical comorbidity.
AB  - Borderline Intellectual Functioning, a diagnostic category in psychiatry, has
      received little attention to date. This condition, present in up to 7% of the
      population, may result in significant functional limitations, especially in
      stressful or novel circumstances, and may coexist with or be eclipsed by other
      mental disorders. Adequate recognition is essential both for strengthening
      dysfunctional cognitive processes and for enhancing social competence, as well as
      for facilitating overall adaptive development, especially in the juvenile
      population.

PMID- 11227627
TI  - Analysis of a managed psychiatric disability program.
AB  - The cost of mental illness to employers has been well documented; however,
      efforts to effectively reduce the costs of psychiatric disability are adversely
      affected by the fragmentation of health care services. This report is a case
      study of a program in which a managed behavioral health care organization managed
      the psychiatric disability of a telecommunications company. Compared with a non
      random cohort of claimants not managed under the pilot, the duration of
      disability was reduced by 23% (17.1 days). Patient and provider satisfaction with
      the program was high. This study illustrates the potential for effectively
      reducing the cost of psychiatric disability and the challenges in coordinating
      health care.

PMID- 11227628
TI  - Phosgene exposure: mechanisms of injury and treatment strategies.
AB  - Phosgene (carbonyl chloride, CAS 75-44-5) is a highly reactive gas of historical
      interest and current industrial importance. Phosgene has also proved to be a
      useful model for the study of those biochemical mechanisms that lead to
      permeability-type pulmonary edema (adult respiratory distress syndrome). In turn,
      the study of phosgene-induced adult respiratory distress syndrome has provided
      insights leading to revised treatment strategies for exposure victims. We
      summarized recent findings on the mechanisms of phosgene-induced pulmonary edema
      and their implications for victim management. In light of that research, we also
      provide a comprehensive approach to the management and treatment of phosgene
      exposure victims.

PMID- 11227629
TI  - The impact of psychosocial work factors on musculoskeletal pain: a prospective
      study.
AB  - A prospective cohort study investigated how psychosocial work factors predict
      musculoskeletal pain. A total of 721 workers at 226 automobile repair garages
      answered two questionnaires distributed with a 1-year interval. The predictor
      variables were psychological demands, decision authority, social support, and
      management support. The outcome variables were neck pain, low back pain, and an
      index of pain from seven different parts of the body in the past 30 days. The
      best predictors were low decision authority and management support. Low decision
      authority predicted neck pain, low back pain, and total musculoskeletal pain when
      adjusted for the effect of the respective musculoskeletal pain measured in the
      first survey, for age, and for gender. Low management support predicted both low
      back pain and general musculoskeletal pain. The study indicates that psychosocial
      factors at work may predict musculoskeletal pain.

PMID- 11227630
TI  - Neurological effects in workers exposed to manganese.
AB  - The purpose of this study was to examine the effects on the nervous system in
      enamels-production workers who have low levels of and long exposure to manganese
      (Mn). The study included 138 Mn-exposed workers and 137 controls who received
      questionnaires on symptoms, a battery of psychological tests, and assessments of
      blood concentrations of metal. The exposure levels to airborne Mn concentrations
      were determined by personal and stationary samplings. The mean duration exposure
      to Mn was 19.87 years (SD +/- 9). The workers exposed to Mn reported more
      nonspecific subjective complaints than the control group. No effect of Mn
      exposure was indicated by the results of any of the neuropsychological tests. The
      Mn workers did not have higher concentrations of Mn in blood than the controls.
      Exposures of workers currently working with Mn averaged 57 micrograms/m3
      respirable (personal samplings) and 12 g/m3 (stationary samplings). In
      conclusion, long exposure to low levels of Mn (approximately 200 micrograms/m3),
      as induced in our study, showed no significant disturbance of neurological
      performance.

PMID- 11227631
TI  - Cancer incidence among Danish workers exposed to trichloroethylene.
AB  - Human evidence regarding the carcinogenicity of the animal carcinogen
      trichloroethylene (TCE) is limited. We evaluated cancer occurrence among 803
      Danish workers exposed to TCE, using historical files of individual air and
      urinary measurements of TCE-exposure. The standardized incidence ratio (SIR) for
      cancer overall was close to unity for both men and women who were exposed to TCE.
      Men had significantly elevated SIRs for non-Hodgkin's lymphoma (SIR = 3.5; n = 8)
      and cancer of the esophagus (SIR = 4.2; n = 6). Among women, the SIR for cervical
      cancer was significantly increased (SIR = 3.8; n = 4). No clear dose-response
      relationship appeared for any of these cancers. We found no increased risk for
      kidney cancer. In summary, we found no overall increase in cancer risk among TCE
      exposed workers in Denmark. For those cancer sites where excesses were noted, the
      small numbers of observed cases and the lack of dose-related effects hinder
      etiological conclusions.

PMID- 11227632
TI  - Incidence and risk of work-related fracture injuries: experience of a state
      managed workers' compensation system.
AB  - Incidence rates of occupational fractures at various anatomic sites and
      associated risk factors have not been well documented. We identified 3490 work
      related fractures from a West Virginia Workers Compensation database that
      occurred between July 1, 1994, and June 30, 1995. The annual incidence rate was
      55 per 10,000 workers, which is substantially higher than the work-related
      fracture rates reported previously. The incidence rate of fracture was highest in
      the agricultural sector, followed by the mining, construction, and manufacturing
      sectors (202.0, 165.2, 116.7, and 88.0 per 10,000 workers, respectively). The age
      specific gender distribution comparing fracture and non-fracture injuries showed
      a bimodal distribution, with greater proportions of female employees at the
      younger and older age groups. Fracture of the phalanges was the most common,
      followed by fractures of the foot bone and carpal bone (15.8, 9.5, and 7.9 per
      10,000 workers, respectively). In a multiple logistic regression analysis, age,
      gender, occupation, caught in-between objects, fall, struck by or against object,
      and vehicle collision were significant independent predictors of fracture (all
      sites combined). We believe work-related fractures to be a bigger problem than
      previously reported. The association among gender, age, occupation, and causes of
      fractures identified in this study will be useful in developing gender- and
      occupation-specific prevention intervention.

PMID- 11227633
TI  - Prioritization of occupational sentinel health events for workplace health and
      hazard surveillance: the Pan American Health Organization experience.
AB  - Within the ongoing strategy of the Workers' Health program at the Pan American
      Health Organization on strengthening surveillance in the field of workers' health
      in the Americas (the Region), a project was conducted in July 1999 in Washington,
      D.C. The objectives of the project were to discuss the problems found in the
      surveillance of workers' health, to develop a methodology and use it to
      prioritize and select the top three occupational sentinel health events for
      incorporation into the surveillance systems in the Region, and to develop the
      initial protocols for establishing the surveillance systems for the three chosen
      occupational sentinel health events. The Pan American Health Organization invited
      24 occupational health experts from the Region to participate in the project.
      Over an intensive 3-day period, the experts heard reports of workplace
      surveillance activities in the various countries in the Region; developed
      prioritization methods; identified and prioritized a list of occupational
      sentinel health events; and developed three surveillance protocols, one each for
      occupational fatal injuries, pesticide poisoning, and low back pain. The results
      on the prioritization of occupational sentinel health events and the development
      of surveillance protocols are reported in this article.

PMID- 11227634
TI  - Assessing mercury health effects in gold workers near El Callao, Venezuela.
AB  - Mercury exposure and health status were examined in 40 gold workers in the area
      surrounding El Callao, Venezuela. Concentrations of mercury in workplace air were
      measured on 3 successive days, and spot urine and hair samples were also taken
      for analysis. Subjects underwent a physical examination and completed a
      questionnaire regarding employment history, work activities involving mercury
      exposure, use of protective clothing and equipment, and frequency of 37 symptoms
      associated with mercury toxicity. A complete set of health data was collected for
      29 of the subjects. Use of protective equipment was limited, and 17.9%, 24.1%,
      and 48.3% of subjects had mercury concentrations in air, hair, and urine,
      respectively, above contemporary occupational exposure guidelines. Physical
      examination found the workers to be generally healthy and without overt symptoms
      of mercury toxicity. The frequency of psychoneurological, gastrointestinal,
      cardio-respiratory, and dermal symptoms was unrelated to any of the measures of
      mercury exposure. Two subjects had modestly elevated urinary levels of N-acetyl
      beta-D-glucosaminidase. Despite substantial occupational exposure to mercury
      among a number of the subjects, few adverse health effects were observed that
      were plausibly related to mercury.

PMID- 11227635
TI  - Cancer incidence among employees at a petrochemical research facility.
AB  - This investigation evaluated cancer incidence among workers at a petrochemical
      research facility in Illinois. A cluster of brain cancer and other intracranial
      tumors had occurred at the facility before the study began. The subjects were
      5641 people who had worked at the facility from 1970 through 1996 and who had
      lived in Illinois at any time between 1986 and 1997. Data on cancer cases came
      primarily from the Illinois State Cancer Registry. Analyses compared the 1986-to
      1997 cancer incidence rates of employees with Illinois general population rates.
      Subjects had 18% fewer than expected total cancers (125 observed/153 expected
      cases; standardized incidence ratio [SIR], 82; 95% confidence interval [CI], 68
      to 98), which was primarily attributed to a large deficit of lung cancer (10/26;
      SIR, 39; CI, 19 to 72). Brain cancer was increased in the overall study group
      (6/2.7; SIR, 222; CI, 81 to 484). This excess was restricted to white men who
      were scientists or technicians for one of the three companies at the facility
      (6/0.8; SIR, 750; CI, 275 to 1633); all cases in this group had worked in the
      "500 building complex" (6/0.6; SIR, 968; CI, 355 to 2106). Subjects also had an
      increased incidence of thyroid cancer (7/2.6; SIR, 265; CI, 106 to 546) that was
      not concentrated in particular occupational or building groups. The brain cancer
      incidence patterns indicated that an unidentified occupational exposure might
      have been responsible for the excess. Chance, socioeconomic factors leading to
      better case detection in facility employees than in the general population, and
      confounding by potential nonoccupational risk factors are plausible explanations
      of the observed increase in thyroid cancer.

PMID- 11227636
TI  - Bank One's worksite-based asthma disease management program.
AB  - Non-occupational asthma is a common disease affecting approximately 6% of the US
      population. Asthma accounts for an estimated 3 million workdays lost each year in
      the United States and for reduced employee job productivity. Although asthma
      disease management programs are relatively common in managed care organizations,
      they generally have not been offered at the workplace. A total of 168 employees
      with asthma were identified, and 76 participated in a worksite asthma disease
      management program. Of them, 41 (53.9%) completed an Asthma Therapy Assessment
      Questionnaire (ATAQ) at baseline, post-program (2 months), 4 months, and 12
      months. The total ATAQ Index declined from 3.59 at baseline to 2.76 at 12 months
      (p < 0.01). After the program, significantly more employees reported using
      controller medications (the desired behavior) rather than reliever medications. A
      worksite-based disease management program for asthma should reduce medical care
      costs and absenteeism and improve worker productivity.

PMID- 11227637
TI  - Management of musculoskeletal pain in the workplace.
AB  - Occupational Safety and Health Administration recordable upper-extremity
      musculoskeletal pains or disorders account for a significant number of work
      related illnesses in the US workforce. Although the concept of musculoskeletal
      disorder prevention is appealing, little has been done to demonstrate the
      successful application and benefit of these programs. In 1995, an aircraft
      manufacturer established a unique risk-management program for new employees based
      on the CtdMAP individual risk assessment instrument. In 1998, a subgroup was
      prospectively studied for medical management on the basis of individual risk
      scores. Outcome measures were compared for the risk assessment group, the matched
      control group, and the total company. Employer-estimated savings in direct
      workers compensation costs were $2.42 million, and estimated indirect savings
      were over $13.5 million during the study.

PMID- 11227639
TI  - Imaging the results of antiangiogenesis therapy.

PMID- 11227638
TI  - Public health risks of railroad hazardous substance emergency events.
AB  - The number of railroad events reported to the Agency for Toxic Substances and
      Disease Registry's Hazardous Substances Emergency Events Surveillance system
      increased from 84 in 1993 to 177 in 1998. Comparisons of data on railroad and non
      railroad events were made. The results overall indicated a greater potential
      impact of railroad events on public health. A median number of 2039 persons were
      living within a 1-mile radius of railroad events versus 982 for non-railroad
      events. The percentage of events during times when people are more likely to be
      home was also greater for railroad events. Railroad event victims were more
      likely to need hospital treatment than non-railroad event victims, which
      suggested the need for better community planning, reevaluation of current federal
      regulations and priorities for railroad hazardous material transport, and
      enhanced railroad industry commitment to safety.

PMID- 11227640
TI  - Sonographic evaluation of orthotopic bladder tumors in mice treated with TNP-470,
      an angiogenic inhibitor.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to determine the
      feasibility of using transabdominal ultrasonography (US) to monitor tumor growth
      and response to therapy in a mouse model of orthotopic bladder carcinoma.
      MATERIALS AND METHODS: Human bladder carcinoma cell suspensions were injected
      into the bladders of 18 SCID mice, allowed to grow for 3 weeks, and monitored
      weekly with gray-scale US. After 23 days, five animals were treated with TNP-470,
      an angiogenic inhibitor, and five control animals were treated with saline
      solution. US images were evaluated for tumor location, size, and neovascularity.
      All untreated animals (n = 8) were imaged and sacrificed at 25 days. Eight of the
      treated animals were imaged and sacrificed after 14 days of treatment. US
      findings for both groups were compared with autopsy findings. RESULTS: While
      saline-treated tumors continued to grow, the growth of TNP-470-treated tumors was
      arrested within 7 days of therapy (P < .02). Tumors as small as 1.5 mm were
      identified prospectively with US. US volume estimates correlated well with
      autopsy volume measurements (r2 = 1.0, P < .0001). Although tumor neovascularity
      was identified in every animal, the pattern of neovascularity did not correlate
      with tumor volume or therapy. CONCLUSION: US can provide accurate intermediate
      end points for monitoring experimental intraabdominal tumor growth and response
      to therapy in the mouse model.

PMID- 11227641
TI  - Diagnostic performance of trauma US in identifying abdominal or pelvic free fluid
      and serious abdominal or pelvic injury.
AB  - RATIONALE AND OBJECTIVES: This study assessed the ability of a six-point trauma
      ultrasound (US) evaluation (a) to identify the presence of free fluid in the
      abdomen or pelvis, with computed tomography (CT) and laparotomy used as
      diagnostic standards and (b) to predict the presence of abdominal or pelvic
      injury, particularly injury requiring surgical intervention. MATERIALS AND
      METHODS: Of 156 patients who underwent US evaluation for free fluid after
      sustaining blunt and penetrating trauma, 147 were entered into the prospective
      study and underwent follow-up CT and/or laparotomy (n = 79), in-hospital
      observation, or outpatient examination. RESULTS: The sensitivity, specificity,
      positive predictive value, negative predictive value, and overall accuracy of US
      for identifying abdominal or pelvic free fluid were 69%, 100%, 100%, 95%, and
      95%, respectively. The corresponding values for predicting abdominal and pelvic
      injury on the basis of free fluid status alone were 57%, 99%, 80%, 96%, and 95%,
      respectively. Performing repeated US examinations in patients with deteriorating
      clinical status decreased the false-negative rate by 50%, increasing the
      sensitivity for free fluid detection to 85% and the negative predictive value to
      97%. Similarly, the sensitivity and negative predictive value for detection of
      injury increased to 71% and 97%, respectively. A learning curve was also
      observed, with 67% of the false-negative findings occurring in the first 3 months
      of the 19-month study. CONCLUSION: A six-point trauma US evaluation can reliably
      identify abdominal and pelvic free fluid, which can be a reliable indicator of
      abdominal or pelvic injury. Scanning conditions must be optimized, and the
      approach to clinical management must be cautious.

PMID- 11227642
TI  - Economic consequences of diagnostic imaging for vocal cord paralysis.
AB  - RATIONALE AND OBJECTIVES: The purpose of this retrospective study was to estimate
      the economic consequences of evaluating suspected vocal cord paralysis with
      magnetic resonance (MR) imaging and computed tomography (CT). MATERIALS AND
      METHODS: Reports from MR imaging (n = 30) or CT (n = 19) studies of the neck in
      49 patients were retrospectively reviewed for causes of vocal cord paralysis. The
      patients were divided into high-suspicion (n = 20) and low-suspicion (n = 29)
      groups, based on the presence or absence of a clinically detectable abnormality
      other than vocal cord immobility. Clinic and inpatient charts were examined to
      determine the work-up in all cases. The Medicare Resource-based Relative Value
      Scale was used to estimate the costs of most procedures. RESULTS: The high
      clinical-suspicion group included nine true-positive, four false-positive, seven
      true-negative, and no false-negative cases. Further work-up was performed in
      seven true-positive, three false-positive, and one true-negative cases. The total
      cost of immediate diagnostic work-up in these 20 patients, including MR imaging
      and/or CT, was $20,737 ($2,304 per true-positive case). The low-suspicion group
      included two true-positive, nine false-positive, 18 true-negative, and no false
      negative cases. Further work-up was performed in both true-positive, four false
      positive, and two true-negative cases. The total cost of immediate diagnostic
      work-up in these 29 patients was $21,698, (mean, $748; $10,849 per true-positive
      case). CONCLUSION: The average cost of finding space-occupying lesions in
      patients with vocal cord paralysis is more than 4.5 times higher in patients
      without suspicious antecedent clinical findings than in those with such a
      history. The benefits of obtaining negative findings and of detecting a small
      number of space-occupying lesions should be weighed against the costs of such
      examinations and of additional work-up for false-positive findings.

PMID- 11227643
TI  - Accuracy of MR imaging for staging prostate cancer: a meta-analysis to examine
      the effect of technologic change.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to summarize the accuracy
      of magnetic resonance (MR) imaging for staging prostate cancer and to determine
      the effect of high magnetic field strength, use of the endorectal coil, use of
      fast spin-echo (SE) imaging, and study size on staging accuracy. MATERIALS AND
      METHODS: A literature search and review yielded 27 studies comparing MR imaging
      to a pathologic standard in patients with clinically limited prostate cancer.
      Subgroup analyses examined magnetic field strength, use of an endorectal coil,
      use of fast SE imaging, publication date, and study size. RESULTS: A summary
      receiver operating characteristic curve for all studies had a maximum joint
      sensitivity and specificity of 74%. At a specificity of 80% on this curve,
      sensitivity was 69%. Subgroup analyses showed that fast SE imaging was
      statistically significantly more accurate than conventional SE techniques (P <
      .001). Unexpectedly, studies employing higher magnetic field strength and those
      employing an endorectal coil were less accurate. CONCLUSION: Seemingly small
      technologic advances may influence test accuracy. Early and small studies,
      however, may overstate accuracy because of publication bias, bias in small
      samples, or earlier studies being performed by the experts who developed the
      technology itself.

PMID- 11227644
TI  - Morphologic degeneration of human microvascular endothelial cells induced by
      iodinated contrast media.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to characterize the
      adverse effects of iohexol and ioxaglate on human microvascular endothelial
      cells, which may result in phlebitis, pain, and thrombosis. MATERIALS AND
      METHODS: The degree of morphologic degeneration and of lactate dehydrogenase
      (LDH) efflux into the extracellular medium (as an index of cell viability) were
      determined in endothelial cell culture exposed for 10, 30, or 60 minutes to
      ioxaglate or iohexol (ionic and nonionic contrast media, respectively) at iodine
      concentrations of 100 or 150 mg/mL. RESULTS: Ioxaglate induced concentration- and
      time-dependent morphologic degeneration, including shrinkage and loss of the cell
      tip in 20%-80% of endothelial cells; iohexol did not. After 60 minutes of
      exposure, ioxaglate at the higher concentration (150 mg iodine per milliliter)
      significantly increased the LDH signal (ie, the percentage of LDH released), to
      20%. CONCLUSION: The present findings demonstrate that ioxaglate but not iohexol
      causes morphologic degeneration of the microvascular endothelial cells. This
      direct cytotoxic action of ioxaglate probably causes endothelial cell
      dysfunction, closely associated with the occurrence of phlebitis, pain, and
      thrombosis.

PMID- 11227646
TI  - Personal diary: a research PhD's perspective.

PMID- 11227645
TI  - Contrast-enhanced B-mode US angiography in the assessment of experimental in vivo
      and in vitro atherosclerotic disease.
AB  - RATIONALE AND OBJECTIVES: This study was performed to (a) test the hypothesis
      that filling the arterial lumen with echoes at B-mode ultrasound (US) enables the
      assessment of wall and luminal abnormalities and (b) compare contrast material
      enhanced B-mode US with color and power Doppler US angiography. MATERIALS AND
      METHODS: Atherosclerotic lesions were created in 14 rabbit aortas and imaged with
      color Doppler and B-mode US before and after the intravenous administration of
      0.3 mL of AF0150, a US contrast agent. In addition, four replicas of diseased
      human carotid arteries were immersed in a tissue-mimicking phantom and imaged
      with B-mode and color and power Doppler US before and after the administration of
      1 mL of AF0150 per liter of porcine blood. Radiopaque plastic casts of the rabbit
      aortas and contact radiographs of the plastic replicas served as standards.
      RESULTS: Although color and power Doppler US allowed immediate localization of
      the lumen, precise estimation of stenoses and reliable visualization of surface
      irregularities were not possible. After AF0150 administration, angiogram-like
      images of the lumen were created with B-mode US, allowing rapid assessment of the
      entire vessel lumen and wall. Consequently, luminal stenoses were more accurately
      measured than with unenhanced B-mode US (r2 = 0.94, P < .0001 vs r2 = 0.21, P =
      .25) or Doppler (r2 = 0.42, P < .03). In addition, plaques and ulcerations were
      visible only with contrast-enhanced B-mode US. CONCLUSION: Microbubbles fill the
      arterial lumen with echoes at B-mode US, creating an angiogram-like image. The
      ability to visualize the inner and outer surfaces of the vascular wall improved
      the evaluation of luminal and wall abnormalities.

PMID- 11227647
TI  - Changes in the job market for interventional radiology as detected through a help
      wanted index of job advertisements.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to study trends in the
      job market in interventional radiology. MATERIALS AND METHODS: Each job
      advertisement for a diagnostic radiologist in the American Journal of
      Roentgenology and Radiology between January 1991 and December 1999 was coded by
      practice type (academic vs private), location, and subspecialty. Positions for
      interventional radiologists were compared with positions for noninterventional
      radiologists. Data from the first 48 months (January 1991 through December 1994)
      were compared with data from the second 48 months (January 1995 through December
      1998). Data from 1999 were grouped separately. RESULTS: The nadir for all
      noninterventional and interventional radiology positions was seen in July 1995,
      and both areas have experienced great recovery since then. In December 1999, the
      last month of data collection, the absolute peak number of advertisements for
      interventional radiologists was reached. In fact, during the last half of the
      decade, an increasing percentage of jobs advertised for diagnostic radiologists
      was specifically for interventional radiologists. Statistically significant
      trends also occurred toward the private sector and toward positions in the
      Midwest and California. CONCLUSION: With a help-wanted index, dramatic shifts
      toward the private sector and toward jobs in the Midwest and California were
      demonstrated in the interventional radiology job market.

PMID- 11227648
TI  - The National Institute of Biomedical Imaging and Bioengineering becomes a
      reality.

PMID- 11227649
TI  - [Resident physician training in the digestive system. The point of view of the
      residents].
AB  - AIM: To evaluate various aspects of current training of Spanish residents in
      gastroenterology. METHOD: An anonymous postal questionnaire was sent to fourth
      year resident physicians in Spanish hospitals with accredited gastroenterology
      residency programs. RESULTS: Forty residents in the fourth year (53% offered
      positions), four from the second year and one from the first year (20 men, 25
      women) answered the survey. Mean age was 29.7 years (26-42 years). Fifty-one
      percent of the departments did not have ultrasonography facilities apart from
      those in the radiology department. Endoscopic retrograde cholangiopancreatography
      (ERCP) was available in all the departments but in 55% of these, residents did
      not receive training in this technique. Forty-one percent of residents did not
      know the objectives of the various training periods. Eighty-four percent
      evaluated the pressure of clinical work as "intense" or "very intense" with 67%
      reporting that it disturbed their training "seriously" or "very seriously" and
      71% that it disturbed their personal lives. Supervision in ultrasonography,
      endoscopy and clinical work were mainly evaluated as "good" or "very good".
      Supervision was rated lower in outpatient departments and while on duty. Forty
      two percent of residents rated the supervision of the personal tutor as
      "average". Seventy-six percent were "fairly" or "very interested" in the
      introduction of "areas of specific training". CONCLUSIONS: The quality of
      residents' training in general and of gastroenterology training in particular is
      high. There are, however, several aspects which could be improved.

PMID- 11227650
TI  - [Azathioprine and 5-ASA in the prevention of postoperative recurrence of Crohn's
      disease].
AB  - Recurrence of Crohn's disease (CD) lesions in the neo-ileum after apparently
      curative resection frequently occurs after surgery. The most appropriate
      prophylactic treatment has not been clearly defined. This study evaluated the
      efficacy of 5-ASA and azathioprine in decreasing postoperative recurrence and
      analysed the presence of variables associated with recurrence. Thirty-nine
      patients (mean age 32.8 years, range 18-61) with a history of ileal or ileocecal
      surgical resection were studied. They received 5-ASA (3 mg/day) or azathioprine
      (50 mg/day) immediately after the operation and for 2 years thereafter. Patients
      were followed clinically (Crohn's disease activity index) and serologically every
      3 months and by imaging methods every 6 months. The latter included colonoscopy
      with ileoscopy and if not available, small bowel barium or ultrasonographic
      study. Laboratory tests included ESR, C-reactive protein, white blood cell and
      platelet count, fibrinogen and albumin. The end-point evaluated included clinical
      recurrence (CR), serological recurrence (SR: alteration of at least three of the
      above-mentioned variables) and morphologic recurrence (MR: endoscopic recurrence
      > 1 according to Rutgeerts score or radiological or ultrasonographic recurrence).
      Eighteen patients received azathioprine and 21 received 5-ASA. Thirty-four
      patients were evaluated. The cumulative proportion of patients with recurrence
      was 29% (CR), 35% (SR) and 50% (MR). Statistical analysis did not show
      significant differences between the two groups. Twenty-seven patients completed
      the 2-year study (11 in the azathioprine group and 16 in the 5-ASA group). Crude
      relapse rates were 37% (CR), 44% (SR) and 69% (MR) in the 5-ASA group and 36%
      (CR), 45% (SR) and 64% (MR) in the azathioprine group. No statistically
      significant differences were observed between groups. No variables associated
      with recurrence were detected. In conclusion, treatment does not prevent a high
      percentage of postsurgical recurrence. 5-ASA (3 g/day) and azathioprine (50
      mg/day) showed similar efficacy in the prevention of recurrence.

PMID- 11227651
TI  - [Esophageal perforations. Presentation of 23 cases].
AB  - AIM: Esophageal perforations are the most serious perforations of the digestive
      tract and their treatment remains controversial. The aim of this study was to
      analyse the outcome of patients with esophageal perforations given surgical and
      conservative treatment. PATIENTS AND METHODS: Retrospective study of 23 patients
      with esophageal perforations, 8 cervical (35%) and 15 thoracic (65%). Medical
      treatment was indicated in patients who fulfilled Cameron's criteria (minimal
      signs of clinical sepsis; disruption contained in the mediastinum; drainage of
      the cavity back into the esophagus; minimal symptoms). The remaining patients
      underwent surgery. RESULTS: Two patients with cervical perforations (25%) met
      Cameron's criteria. Evolution after conservative treatment was favourable. The
      remaining patients (75%) were surgically treated: simple closure of the
      perforation was performed in four and drainage of the cervical abscess in two.
      Two of the patients who underwent surgery presented pleural hemorrhage, one of
      which was associated with pneumonia. Four patients with thoracic perforation
      (27%) met the criteria for conservative treatment. One presented respiratory
      distress syndrome during treatment and required intensive care. Evolution was
      favorable in all. The remaining 11 patients (73%) received surgical treatment: in
      five (46%) simple closure of the perforation was performed, in three (27%)
      bipolar exclusion was performed and in the remaining patients, other techniques
      were used. Morbidity was 82% (nine patients) mainly due to pneumonia and
      mortality was 46% (five patients). CONCLUSIONS: Treatment of esophageal
      perforation should be individualized. Conservative treatment should be considered
      in patients meeting Cameron's criteria as their evolution is favorable, with low
      morbidity and mortality and surgery is not necessary.

PMID- 11227652
TI  - [Crohn's disease and ascites].
AB  - Crohn's disease is not usually included among the causes of ascites. Although
      cases of Crohn's disease presenting as ascites have occasionally been described,
      the appearance of ascites during follow-up, with no relationship with other
      complications of the disease, such as thrombosis of the suprahepatic veins, has
      not been previously described. We present the case of a 36-year-old female
      patient with Crohn's disease who presented ascites during evolution. Evacuative
      paracenteses were required. No causes apart from Crohn's disease were found.
      Ascites followed a parallel course to acute episodes of this disease.

PMID- 11227653
TI  - [Idiopathic chronic pancreatitis (with diffuse stenosis of Wirsung's duct) in
      ulcerative colitis].
AB  - We describe a case of chronic idiopathic pancreatitis associated with ulcerative
      colitis. Pancreatitis is a rare extra-intestinal manifestations of inflammatory
      bowel disease. Chronic idiopathic pancreatitis associated with ulcerative colitis
      are usually painless, without calcification, with stricture of the main
      pancreatic duct and with severe exocrine pancreatic insufficiency.

PMID- 11227654
TI  - [Can specialized medical training in Spain be improved?].

PMID- 11227655
TI  - [Gene therapy for liver diseases].

PMID- 11227656
TI  - [Long-term results of surgical anastomosis in chronic pancreatitis].

PMID- 11227657
TI  - [Training in cannulation of the bile ducts using endoscopic retrograde
      cholangiopancreatography].

PMID- 11227658
TI  - [Pulmonary microlithiasis-analysis of a case].
AB  - The pulmonary microlithiasis is a very rare disease, and each new patient present
      a special interest. It is given an opportunity to discuss some new aspects of the
      etiology and pathogenesis which are unclear. This case concerns a woman (42 years
      old) in whose case some particularities in the clinical course have been analyzed
      and discussed. The essential in the clinical course was practically lack of
      clinical manifestation and disturbances during a very long period--about 25 years
      from the beginning of the disease, and very fast development during last year,
      manifested by the pulmonary deficiency. It was also marked the absence of
      respiratory infection during this long unmanifested period. The lack of the
      familial tendency and occupational noxious in this case rise the question about
      some new aspects of the etiology and pathogenesis of the disease. Namely, the
      disturbances in the recyclation of the pulmonary surfactant as a clue moment in
      the development of the disease.

PMID- 11227659
TI  - [Case of necrotizing enteritis as the first symptom of systemic lupus
      erythematosus].
AB  - The aim of this work is to describe a case of necrotising enteritis as a first
      presentation of a systemic lupus erythematosus (SLE). The patient has undergone
      two laparatomies with resection of a part of the small intestine because of a
      clinically relevant intestinal obstruction. Distended intestinal loops, inflammed
      serosa and mesenterial lymphadentis have been found during the operations. The
      histological examination has proved phlegmonous enteritis with hyperplasia of the
      lymph follicles and infiltration with plasmocytes, lymphocytes and eosinophils.
      Numerous biochemical, immunological, microbiological, ultrasound and X-ray
      investigations have not been helpful for the diagnosis. The appearance of a
      nephrotic syndrome in the course of the disease and the consequent renal biopsy
      have led to confirmation of the diagnosis SLE. The immunosupressive and
      corticosteroid treatment have resulted in fully recovery of the patient.

PMID- 11227660
TI  - [99mTcDTPA-aerosol clearance in early diagnosis of pulmonary changes in patients
      with active systemic lupus erythematosus].
AB  - Nineteen patients with active SLE and a control group of 20 healthy persons were
      investigated. We have made to all of them 99mTcDTPA-aerosol scintigraphy and the
      following pulmonary functional tests--Dc CO, Dm, Vc, HRCT. Accelerated clearance
      of 99mTcDTPA was found in all patients with active SLE. The half-elimination time
      T1/2 was shortened and varied between 22.6 +/- 4.7 min for the right one. It
      wasn't established correlative dependence between 99mTcDTPA and the pulmonary
      functional tests. In 36.8% of the patients HRCT was normal, while 99mTcDTPA
      clearance was accelerated. This fact shows, that 99mTcDTPA-aerozsol scintigraphy
      is more sensitive method for early diagnosis of pulmonary changes, than the
      pulmonary functional tests and HRCT.

PMID- 11227661
TI  - [Parenchymal hepatic cells in bile].
AB  - The presence of particular cells, discussed in literature as disintegrated
      parenchymal hepatic cells makes impression during a cytological study. We
      examined 21 patients with chronic active hepatitis. They had the above described
      cells found in the bile sediment by means of light microscope. The sediments were
      studied with electronic microscope as well. Ultrastructural proofs of the fact
      that these cells originate from hepatic parenchyma were found in 3 of the cases.
      The most important evidences are: the structure of the granular endoplasmic
      riticulum and of the mitochondria, as well as the precipitation of
      microcorpuscles.

PMID- 11227662
TI  - [Enalapril-clinical experience in Bulgaria].
AB  - The authors present the results of clinical trail about treatment of arterial
      hypertension with ENAP (Enalapril) fo KRKA in centers of Bulgaria. Enalapril is
      ACE-inhibitor usually administered orally once daily, decreases blood pressure by
      lowering peripheral vascular resistance without increasing heart rate or output.
      In this clinical trail are given results about blood pressure, heart rate and
      biochemical indexes. The most frequent adverse events--headache, dizziness,
      orthostatic effects, abdominal pain e.t.s. occurring in less than 10%. More
      important side effects like dry persistent cough occurring in 8.6%. The results
      of clinical trail define high efficacy and good tolerability of ENAP in the
      treatment of arterial hypertension.

PMID- 11227663
TI  - [Light chain diseases--pathogenetic forms, diagnostic criteria. A suggestion for
      classification].
AB  - The clinical significance of the BJ-protein is quite variable: from an
      asymptomatic course of the light chain proteinuria for a long period of time to
      specific tissue deposits with serious organ damages and dysfunction. On the basis
      of literature data a classification of the light chain diseases is proposed: 1.
      Essential (bening) BJ-proteinuria; 2. Smoldering BJ-myeloma; 3. Light chain
      disease--BJ myeloma; 4. Light (and heavy) chain deposition disease: LC granular
      thick deposits mostly k type on electron microscopy, belonging to the constant
      region of the polypeptide chain and actively reacting with antiserums, not
      possessing tincturial properties; 5. LC cast nephropathy--LC coprecipitates in
      the tubular system; 6. LC crystaline deposition disease--specific crystaloid
      structures (in the Fanconi syndrome and experimental nephropathies); 7. AL
      amyloidosis: LC precursor mostly lambda type from the variable region with
      specific fibrilar structure and typical tincturial properties. The suggested
      classification would resolve the diagnostic difficulties and determine the
      correct therapeutic management.

PMID- 11227664
TI  - [Activity of vancomycin and teicoplanin against clinical isolates of
      Staphylococcus aureus in the period 1994-1999].
AB  - Since the emergence of the methicillin-resistant S. aureus (MRSA) in the 1960's,
      glycopeptides (Vancomycin and Teicoplanin) has been the drugs of choice and
      commonly the sole antimicrobial agents available for the treatment of serious
      MRSA and other Gram-positive infections. The emergence of S. aureus with
      intermediate vancomycin-resistance after 1997 threatens to return us to the era
      before the development of the antibiotics. Prevention of the further spread of S.
      aureus strains with intermediate and eventually with full glycopeptide resistance
      requires enhanced laboratory methods to detect resistance. A total of 361 S.
      aureus clinical isolates (177 MRSA and 184 MSSA) obtained from 1994 to 1999 in
      eleven Bulgarian hospitals located in geographically distinct areas of the
      country were enrolled in the study. Minimal inhibitory concentrations of
      Vancomycin and Teicoplanin were determined by agar-dilution method according to
      NCCLS recommendations. MIC50 and MIC90 for Vancomycin were 0.7 and 1 mg/ml, and
      for Teicoplanin--0.5 and 0.9 microgram/ml. All staphylococcal isolates showed
      sensitivity to Vancomycin and Teicoplanin. MICs of both glicopeptides against
      MRSA and MSSA did not differ significantly.

PMID- 11227665
TI  - [Rare pulmonary (alveolar) diseases--clinico-morphological and etiopathogenic
      aspects].
AB  - Bearing in mind the exceptional rarity of the following three pulmonary diseases:
      pulmonal microlythiasis, proteinosis and primary idiopathic amyloidosis, a review
      of the latest publications in the international scientifical literature about
      their ethiology and pathogenesis has been made. In this context, the latest data
      concerning the role of pulmonary surfactant in their pathogenesis has been
      outlined. The description and re-iteration of the scanty information available
      about these conditions will expand the knowledge of specialists in pulmology and
      of general practitioners in particular who are the first to encounter these
      particularly seldom occurring, and for this reason insufficiently investigated,
      diseases. The new reports regarding the structure, production and recycling of
      pulmonary surfactant clarify to a certain extent the ethiology and pathogenesis
      of the diseases looked upon not long ago as conditions of unsettled ethiology.

PMID- 11227667
TI  - The sympathetic nervous system promotes carbon tetrachloride-induced liver
      cirrhosis in rats by suppressing apoptosis and enhancing the growth kinetics of
      regenerating hepatocytes.
AB  - Norepinephrine is considered to possess potent anti-apoptotic action in
      regenerating hepatocytes. To clarify the role of the sympathetic nervous system
      in apoptosis that occurs in chronic liver damage and following the promotion of
      liver cirrhosis, we studied a carbon tetrachloride (CCl4)-induced liver injury
      model, using spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY), and
      chemically sympathectomized WKY. At 24 h after CCl4 administration. acute damage,
      characterized by vacuolated hepatocytes in the centrilobular zone, was greater in
      SHR than in WKY. This vacuolated change in WKY hepatocytes was significantly
      reduced by chemical sympathectomy with 6-hydroxydopamine (6-OHDA). After 48 h,
      the acute damage was dramatically improved in each animal, without significant
      differences between the three groups. In chronic damage after weekly repetition
      of CCl4 treatment for 4 weeks, fibrosis was evident in SHR, while in the other
      groups there was only scant fibrosis in the centrilobular zone. After 8 weeks'
      repetition of CCl4, liver cirrhosis was seen only in SHR. The incidence of
      apoptotic cells in areas of both acute and chronic damage in WKY, detected by
      terminal deoxynucleotidyl transferase-dUTP nick end labeling, was significantly
      increased in comparison with that in SHR, and was further increased by 6-OHDA
      pretreatment. In contrast, there was significantly greater enhancement of the
      growth of hepatocytes in SHR than in WKY in both acute and chronic damage.
      Moreover. hepatocyte growth kinetics in WKY was significantly inhibited after
      sympathectomy in acute injury, as evidenced by immunohistochemistry for
      proliferating cell nuclear antigen (PCNA). In vitro, the amount of hepatocellular
      apoptosis induced by transforming growth factor-beta1 was significantly decreased
      by incubation with norepinephrine. These findings suggest that the anti-apoptotic
      effect of the sympathetic nervous system increases cell growth kinetics and
      promotes liver cirrhosis in this animal model.

PMID- 11227666
TI  - Mutation at codon 130 in hepatitis B virus (HBV) core region increases markedly
      during acute exacerbation of hepatitis in chronic HBV carriers.
AB  - Mutations within T-cell or B-cell epitopes are suggested to have some influence
      on the clinical course of chronic hepatitis B virus (HBV) infection. To
      investigate the relationship between liver cell injury and heterogeneity of the
      HBV core gene, we focused on the sequence of codon 130, which is located on both
      T- and B-cell epitopes, and serially analyzed the proportion of mutant virus
      (core130Thr) to wild-type virus (core130Pro) during the exacerbation of chronic
      hepatitis B. Sera obtained serially from five HBV carriers who had exacerbation
      of hepatitis, and three asymptomatic HBV carriers (ASCs) with persistently normal
      serum aminotransferase (ALT) values were studied, using the restriction fragment
      length polymorphism (RFLP) method. Core130Pro predominated in the sera in the
      remission state, but core130Thr increased markedly in parallel with ALT elevation
      and decreased again after the ALT peak, followed by the predominance of
      core130Pro, in all the five patients. In one patient, the ratio of
      core130Thr/core130Pro (Thr/Pro) was more than 70% at the ALT peak. On the other
      hand, in sera from the three ASCs core130Pro always predominated, and no
      divergence was identified in the ratio of Thr/Pro. Our data suggest that codon
      130 is one of the most important immunogenic regions in the HBV core gene and
      that elevation of Thr/Pro could be the result of immune selection.

PMID- 11227668
TI  - Early stage gastric MALT lymphoma with high-grade component cured by Helicobacter
      pylori eradication.
AB  - A 68-year-old woman was diagnosed with gastric lymphoma of the mucosa-associated
      lymphoid tissue (MALT) type with a high-grade component. Surgical treatment was
      recommended because of the presence of the high-grade component, but she refused
      surgery. As an alternative, she received Helicobacter pylori eradication
      treatment, which successfully induced regression of the lymphoma. She shows no
      sign of recurrence endoscopically and histologically, as of 29 months after the
      eradication treatment. Moreover, the B-cell monoclonality and Helicobacter pylori
      infection demonstrated at diagnosis has disappeared. This is one of the rare
      cases of gastric lymphoma of the MALT type with a high-grade component cured by
      Helicobacter pylori eradication alone.

PMID- 11227669
TI  - Laparoscopic cholecystofistulectomy for preoperatively diagnosed
      cholecystoduodenal fistula.
AB  - The presence of cholecystoduodenal fistula, a rare condition, has been one of the
      reasons for conversion from laparoscopic cholecystectomy to open cholecystectomy.
      Here we report a patient with cholecystocholedocholithiasis complicated by
      cholecystoduodenal fistula, diagnosed preoperatively and treated by combined
      endoscopic sphincterotomy and laparoscopic cholecystofistulectomy. After the
      removal of multiple bile-duct stones by endoscopic sphincterotomy, the patient
      underwent laparoscopic cholecystofistulectomy. We were able to resect the fistula
      without cleavage, using an endoscopic linear stapling device, because we had been
      able to confirm the site of the fistula preoperatively. The patient's
      postoperative course was uneventful. We conclude that laparoscopic
      cholecystofistulectomy by skilled laparoscopic surgeons can be adopted as a first
      choice treatment for cholecystoduodenal fistula.

PMID- 11227670
TI  - Primary intestinal lymphangiectasia successfully treated with octreotide.
AB  - A 21-year-old man with diarrhea and edema was admitted to our hospital and
      diagnosed with protein-losing enteropathy caused by primary intestinal
      lymphangiectasia. He was placed, in turn, on a low-fat diet, an elemental diet,
      and, subsequently, fasting therapy with total parenteral nutrition (TPN) support.
      However, his symptoms were not relieved, but, rather were exacerbated. On the
      45th day of hospitalization, octreotide therapy was initiated. After 2 weeks of
      treatment, his clinical symptoms, as well as hypoproteinemia and hypoalbuminemia,
      gradually became alleviated. The improvement was confirmed in terms of
      scintigraphy, endoscopy, and histology of the duodenum. The patient remained
      healthy until 6 months after the commencement of octreotide treatment, when he
      discontinued octreotide at his own discretion, at which point the symptoms
      recurred. Resumption of the drug, however, again brought about remission, which
      has continued until the present, March 2000. Thus, octreotide therapy is one
      modality which may be useful for refractory primary intestinal lymphangiectasia.

PMID- 11227671
TI  - Interferon therapy for flare-up of hepatitis B virus infection after emergence of
      lamivudine-induced YMDD motif mutant.
AB  - A 61-year-old man with chronic hepatitis B was treated with interferon (IFN)
      alpha for flare-up after the emergence of a lamivudine-induced YMDD motif mutant.
      The YMDD mutant emerged 13 months after the initiation of lamivudine therapy.
      Despite this, lamivudine therapy was continued. Acute exacerbation occurred 25
      months after the emergence of the YMDD mutant. Treatment with IFN-alpha resulted
      in rapid loss of hepatitis, B virus DNA, resolution of hepatitis, and clinical
      recovery.

PMID- 11227672
TI  - What are the objectives of treatment for intestinal lymphangiectasia?

PMID- 11227673
TI  - Strategy for lamivudine-resistant YMDD mutant-associated chronic hepatitis B.

PMID- 11227674
TI  - Different clinicopathological features of hepatocellular carcinoma in relation to
      causative agents.

PMID- 11227675
TI  - Growth inhibition and apoptosis of gastric cancer cell lines by Anemarrhena
      asphodeloides Bunge.
AB  - In this study, we aimed to determine the growth inhibition and the induction of
      apoptotic cell death brought about by the herb Anemarrhena asphodeloides Bunge in
      gastric cancer cell lines, and to clarify the mechanism of this apoptosis. Water
      soluble ingredients of A. asphodeloides, and the gastric cancer cell lines, MKN45
      and KATO-III, were used in vitro. Growth inhibition, induction of cell death,
      morphological features, the presence of DNA ladders, increases in caspase-3-like
      activity, the effects of a caspase-3 inhibitor on apoptotic cell death, and the
      release of cytochrome c by A. asphodeloides were analyzed. A. asphodeloides
      inhibited the growth and decreased the viability of the gastric cancer cell
      lines. The viability of normal skin fibroblasts in the presence of low
      concentrations of A. asphodeloides was higher than that of gastric cancer cells.
      Apoptotic bodies and DNA ladders were observed to be induced in MKN45 and KATO
      III by A. asphodeloides. The caspase 3 inhibitor, Ac-DEVD-CHO, inhibited the
      apoptotic cell death of gastric cancer cells induced by A. asphodeloides. The
      caspase 3-like activity in MKN45 and KATO-III cells increased after the addition
      of A. asphodeloides. Cytochrome c was released from mitochondria into the cytosol
      8 h after the addition of A. asphodeloides, and reached a peak at 16 h. The peak
      of cytochrome c release was earlier than that of caspase 3-like activity. We
      concluded that A. asphodeloides inhibited the growth of the gastric cancer cell
      lines MKN45 and KATO-III and induced apoptosis. The apoptosis of MKN45 and KATO
      III cells induced by A. asphodeloides was associated with the release of
      cytochrome c from the mitochondria, followed by an increase in caspase 3-like
      activity.

PMID- 11227676
TI  - Melatonin's gastroprotective and antistress roles involve both central and
      peripheral effects.
AB  - Systemic administration of melatonin (5 to 20 mg/kg) has been reported to inhibit
      the induction of acute gastric mucosal lesions by stress or ischemia-reperfusion
      in rats. We recently demonstrated that intracisternal (i.c.) melatonin at low
      doses (1 to 100 ng) dose-dependently decreased acid and pepsin outputs in rats.
      The aim of the present study was to further investigate the peripheral and
      central roles of melatonin in gastric mucosal defense. Using a radioimmunoassay,
      we measured melatonin concentrations in the plasma and cerebrospinal fluid (CSF)
      of the cisterna magna in rats subjected to water immersion restraint stress and
      given intraperitoneal (i.p.) or i.c. injection of melatonin. Water immersion
      restraint stress was followed by a significant duration-related increase in
      peripheral plasma melatonin levels; the stress similarly produced a time
      dependent increase in the extent of gastric mucosal lesions. Administration of
      melatonin (1 or 10 mg/kg, i.p., or 100 ng/10 microl, i.c.) significantly reduced
      the extent of stress-induced gastric damage, by 46%, 67%, and 54%, respectively.
      The effective i.c. dose of melatonin was at least 10,000-fold smaller than the
      effective i.p. dose. Melatonin levels in plasma and CSF after the i.p. injection
      of melatonin at 10 mg/kg were dramatically higher than those after the i.c.
      injection of vehicle or 100 ng of melatonin. Our results suggest that the
      peripheral gastroprotective action of melatonin should be investigated with due
      regard to these central effects.

PMID- 11227677
TI  - Comparison of the efficacy and safety of different formulations of omeprazole
      based triple therapies in the treatment of Helicobacter pylori-positive peptic
      ulcer.
AB  - Little is known about the efficacy and safety of different formulations of
      omeprazole-based triple therapy regimens for the treatment of Helicobacter pylori
      positive peptic ulcer. We compared the efficacy and safety of two formulations of
      omeprazole used in triple therapies in patients with H. pylori-positive active
      peptic ulcer. Seventy-four patients with endoscopically proven H. pylori-positive
      active peptic ulcer were randomized to two groups, each with 37 patients, to
      receive either OAC-I (6 weeks of "A" formulation of omeprazole [20 mg twice
      daily] plus 2 weeks of amoxicillin [1.0 g twice daily] and clarithromycin [500 mg
      twice daily] or OAC-II (6 weeks of "B" formulation of omeprazole [20 mg twice
      daily] plus 2 weeks of the same antibiotics. The H. pylori and ulcer healing
      status were assessed at the baseline and at the 6-week endpoint of therapy.
      Gastrointestinal symptoms, documentation of adverse events, and standard
      laboratory examinations were assessed at each visit. Eradication of H. pylori
      (intention to treat [n = 74]/per protocol [n = 66]) and healing of the ulcer were
      successful in 83.8%/96.9% and 93.8%, respectively, of the OAC-I group patients,
      and in 91.9%/100% and 97.1%, respectively, of the OAC-II group patients (P =
      0.477; P = 0.608). The OAC-I group experienced rapid resolution of symptoms, but
      no significant differences were found between the two groups for number of days
      taken for resolution of gastrointestinal symptoms, adverse events, and laboratory
      findings. The two different formulations of omeprazole used in triple therapy
      regimens produced similar efficacy and safety results after 6 weeks of treatment
      in patients with H. pylori-positive active peptic ulcer.

PMID- 11227678
TI  - Tourniquet and subcutaneous epinephrine reduce blood loss during burn excision
      and immediate autografting.
AB  - Blood loss has been reduced using both tourniquets and epinephrine-injected
      subeschar during burn wound excision. This study quantified and compared blood
      loss in extremities distal to an inflated tourniquet with that after subeschar
      infusion of 1:1,000,000 epinephrine in saline into the trunk or proximal
      extremities. Tangential excision of eschar to viable dermis or fat was followed
      by immediate application of meshed autograft. Blood loss was calculated by
      determining the difference of preoperative and postoperative hemoglobin values
      and the volume of whole blood administered between these. With tourniquets for
      limbs, 2.07 +/- 0.34% of circulating blood volume per 1% body surface excised was
      lost; whereas after epinephrine injection 3.42 +/- 0.39% of blood volume per 1%
      body surface excised was lost (P < 0.05). Both methods effectively reduced blood
      loss when compared with excision followed by delayed autograft application. Where
      there was a choice the tourniquet was more effective.

PMID- 11227679
TI  - The optimal management of pediatric steam burn from electric rice-cooker: STSG or
      FTSG?
AB  - The steam burn caused by an electric rice-cooker is a unique mode of burn injury
      in Asian countries, especially Korea and Japan. This type of burn injury is
      characterized by 1) occurring most frequently on the volar aspect of the hand in
      toddlers younger than 2 years of age (92.8%); 2) the depth of burns are normally
      deep second-degree to third-degree (98%) and usually need surgery at the time of
      injury; 3) flexion contractures of multiple finger joints and web space
      contracture are common sequelae. We hypothesized that primary full-thickness skin
      graft (FTSG) would give more reliable results and eliminate the late
      reconstructive procedures. Between January 1997 and September 1999, 36 patients
      underwent primary FTSG, and the results of this primary FTSG group were compared
      with 124 patients who were treated with split-thickness skin graft (STSG; 79/124;
      63.7%) or by conservative management (45/124; 36.3%), and readmitted for the
      correction of hand deformities between September 1995 and September 1999. In the
      primary FTSG group, 11.1% (4/36) of mild web contractures and 5.5% (2/36) of
      finger joint contractures were documented, and these did not require the
      reconstructive procedure during a follow-up period of 8.8 +/- 4.8 months. In 124
      patients of the primary STSG or conservative group, the mean time interval to
      reoperation was 8.9 +/- 4.0 months and all patients received FTSG for correction
      of late hand deformities. In a retrospective study of the primary STSG group, 42
      of 53 patients (79.2%) received reconstructive procedure during a 5-year follow
      up period. In this report, we introduce the nature of steam burn caused by
      electric rice-cooker and propose that primary FTSG may be a reliable method for
      the treatment of this more severe type of acute burn in pediatric patients.

PMID- 11227680
TI  - Osteocutaneous pedicle flap of the foot for salvage of below-knee amputation
      level after burn injury.
AB  - Lower extremity amputations are occasionally required after high-voltage electric
      and deep thermal burns. The extensive loss of skin and soft tissue after these
      injuries may make it difficult to fashion below-knee amputation that will readily
      tolerate a prosthesis. We have found an osteocutaneous pedicle fillet flap of the
      foot useful in the salvage of below-knee amputation after severe burn injury.
      Three patients have undergone this procedure after burn injury, 1 with burn
      secondary to high-voltage electric injury and 2 after deep thermal burns. All
      became ambulatory with artificial prostheses. There were no postoperative
      infections and no need for further revisions. The osteocutaneous pedicle fillet
      flap of the foot has proven to be a reliable form of below-knee stump coverage in
      patients with extensive soft tissue necrosis after burn injury.

PMID- 11227681
TI  - Barriers to employment among working-aged patients with major burn injury.
AB  - The purpose of this study was to examine the prevalence of preexisting and burn
      related impairments and to describe their association with preburn employment
      status. Data gathered during the acute hospitalization were analyzed on a
      consecutive series of burn patients aged 16 to 64 years (N = 770) enrolled in a
      prospective, longitudinal, multicenter study. Patients who were unemployed before
      the injury were more likely than those who were employed to report being alcohol
      dependent (36 vs 18%), abusing other drugs (22 vs 10%), having received
      psychiatric treatment in the past year (21 vs 6%), and having preexisting
      physical disability (23 vs 3%); all were significant at P < .001). Of the
      unemployed patients who received toxicologic screening at admission, 49% tested
      positive for alcohol and 39% positive for other drugs, percentages that were
      significantly higher than 26 and 31%, respectively, for the employed. With
      adjustment for age, sex, race, and education, variables that were most predictive
      of preinjury unemployment status were preexisting physical disability (odds
      ratio, 51.0; 95% confidence interval, 7.7-336.9) and being alcohol-positive at
      admission (odds ratio, 2.8; 95% confidence interval, 1.2-6.8). Unemployed and
      employed patients also differed significantly in injury patterns and clinical
      outcomes, with inhalation injury and psychiatric distress being more prevalent
      among the unemployed and both hand burns and hand surgery among the employed. The
      greater prevalence of preexisting impairments among survivors who were unemployed
      before the injury helps explain why preburn employment status is such a powerful
      determinant of postburn work outcomes, and suggests the need to include
      psychosocial services in a program of comprehensive rehabilitation.

PMID- 11227682
TI  - The use of 5% mafenide acetate solution in the postgraft treatment of necrotizing
      fasciitis.
AB  - Twenty-nine patients with necrotizing fasciitis who were treated with 5% mafenide
      acetate solution (MAS) as an adjunct after grafting were compared with 45
      patients treated without MAS. Statistical analysis of differences was obtained
      through P values by chi2 testing. The MAS+ (M) and MAS- (C) groups were similar
      in percent skin deficit (M = 7.5%; C = 9.8%), with the extremity being the most
      common area of infection. Streptococcus was the most common single organism but
      polymicrobial infections were the most prevalent (M = 48%; C = 58%). Patients
      with necrotizing fasciitis treated with MAS had fewer debridements per patient (M
      = 3.7; C = 5.4), fewer closure procedures (average per patient: M = 1.2; C =
      1.73) and a higher percent of first-time closures (83 vs 59%; chi2 = 4.26; P =
      0.039). There is a trend toward a lower mortality rate (3.4 vs 13%; chi2 = 2.00;
      P = 0.158). We conclude that MAS is a useful adjunct in necrotizing fasciitis
      wound care protocols.

PMID- 11227683
TI  - Melanocyte repopulation in full-thickness wounds using a cell spray apparatus.
AB  - Melanocyte restoration is critical in reconstituting skin color. We developed a
      spotted (piebald) pig wound model to study methods of restoring melanocytes to
      the epidermis. Paired, full-thickness, porcine wounds were covered with
      nonpigmented, fully expanded, 3:1 meshed, split-thickness skin grafts and were
      sprayed with an epidermal cell suspension. The suspensions were highly pigmented
      skin (HPS) cell isolates for half of the wounds (n = 16) and nonpigmented skin
      (NPS) cell isolates for the remaining wounds (n = 16). Histologic sections showed
      6.0 +/- 3.0 and 15 +/- 4.0 pigmented melanocytes per high-power field on days 8
      and 20 in HPS-treated wounds and no pigmented melanocytes in NPS-treated wounds.
      Melanin pigment was dispersed in all layers of the epithelium for the HPS group
      on day 20 compared with a lack of melanin pigment observed in the NPS group. Cell
      spraying may provide a clinical method to restore color to skin; further work is
      needed to control the expression of melanin.

PMID- 11227684
TI  - The effect of music-based imagery and musical alternate engagement on the burn
      debridement process.
AB  - Management of pain is a primary concern in the treatment of burn patients. The
      intent of this study was to test the efficacy of music-based imagery and musical
      alternate engagement in assisting burn patients in managing their pain and
      anxiety during debridement. Twenty-five patients, 7 years of age and older, who
      were admitted to the Comprehensive Burn Care Center were enrolled in the study,
      which used a repeated-measures design with subjects serving as their own control.
      Subjects were randomly assigned to 1 of 2 groups. Those placed in Group A
      received music therapy intervention during their first dressing change, and no
      music therapy on the following day. Group B received no music therapy
      intervention during their first dressing change and music therapy during their
      next dressing, on the following day. Data were collected at 4 intervals in the
      medical procedure; in the patient's room before transfer to the treatment room,
      in the treatment room during debridement, in the treatment room after
      debridement, and upon returning to the patient's room. The measurements taken
      were pulse, patients' self-report of pain, patients' self-report of anxiety, and
      the nurse's observation of patients' tension. There was a significant reduction
      in the self-reporting of pain in those who received music therapy in contrast to
      those who did not receive music therapy (P < .03). Music therapy is a valuable
      noninvasive intervention for the treatment of pain after burn injury.

PMID- 11227685
TI  - Results of early excision and full-thickness grafting of deep palm burns in
      children.
AB  - The timing and method of treatment of deep palm and finger burns varies widely.
      Our protocol involves performing full-thickness skin grafts (FTSG) in nonhealing
      palm burns. We reviewed the functional and cosmetic results after FTSG to the
      palm. From August 1997 to April 1999, 11 patients (12 palms) underwent excision
      and FTSG within 2 weeks of injury. A panel of medical and nonmedical
      professionals evaluated follow-up pictures of the grafts at 1, 2 to 4, and beyond
      4 months. Parameters used for evaluation were color match with the unburned skin
      (1 = no difference to 4 = large difference), graft thickness (1 = flat to 4 =
      markedly raised), overall appearance (1 = poor to 100 = excellent), and time to
      maturity. Hand function, as assessed by occupational therapy notes, was also
      recorded. All 12 grafted palms had a 100% take and healed with minimal scarring.
      Mean color match scores were 2.4 at 1 month, 1.8 at 2 to 4 months, and 1.6 beyond
      4 months. On the graft thickness scale, grafts were given scores of 2.6, 2.2, and
      1.9 during the same intervals. The overall appearance was 71 at 1 month, 81 at 2
      to 4 months, and 85 beyond 4 months. All grafts except 1 were judged to be mature
      at 2 to 4 months follow-up. Full passive range of motion was attained in all
      grafted hands within the period of 2 to 4 months after operation. Early excision
      and FTSG of deep pediatric palm burns can be performed in the outpatient setting.
      The grafts have an acceptable color match, are minimally raised, and achieve
      excellent cosmetic result. The grafts mature within a few months after surgery to
      allow for rapid return to normal range of motion. FTSG should be considered as a
      first choice for deep palm burns.

PMID- 11227686
TI  - The expression of cyclooxygenase and the production of prostaglandin E2 in
      neutrophils after burn injury and infection.
AB  - Recent studies have demonstrated that neutrophils have the capacity to produce a
      variety of cytokines after stimulation. The synthesis and release of
      prostaglandin E2 (PGE2) via the cyclooxygenase (COX) pathway has been reported to
      occur in activated neutrophils. In the present study, we sought to determine the
      status of COX protein synthesis and PGE2 production in murine neutrophils after
      burn injury. The effect of burn injury on neutrophil COX and PGE2 response to
      infection or lipopolysaccharide (LPS) was also examined. Peritoneal neutrophils
      were obtained from BDF1 mice at 4, 18, 24, and 36 hours after a 15% TBSA full
      thickness scald burn or sham burn. We found that neutrophils from healthy mice
      express a low level of COX-2 protein. Neutrophil COX-2 protein expression in burn
      animals was significantly increased at 4 hours and dramatically decreased at 36
      hours after burn injury. Animals 36 hours after burn and topically infected with
      Pseudomonas Aeruginosa had neutrophil COX-2 expression almost identical to burn
      injury only. Neutrophils harvested from healthy mice cocultured with LPS (1
      microg/ml) had a marked induction of COX-2 protein. Neutrophils 24 hours after
      burn were unresponsive to LPS-stimulated COX-2 enhancement. COX-1 protein was
      strongly expressed constitutively and not affected further by burn injury or LPS.
      The production of PGE2 corresponded with the changes in COX-2 expression for all
      groups of mice. Our data suggested that neutrophils express both COX-1 and COX-2
      and produce PGE2. The effects of burn injury on neutrophil COX-2 protein
      synthesis and PGE2 production suggest that after burn there is a time-dependent
      response. Insights into not only the global cellular response to injury and
      infection but also temporal nature of the response are important in the
      development of the therapeutic treatment strategies for burn patients.

PMID- 11227687
TI  - A retrospective study on the effectiveness of intranasal midazolam in pediatric
      burn patients.
AB  - Pain control is a major issue concerning children admitted for burns. Pain and
      anxiety associated with twice daily wound cleansing and dressing changes are
      difficult to control, especially if there is no intravenous access. We explored
      the effectiveness of intranasal midazolam (INM) combined with intravenous and/or
      oral pain medications prior to painful treatments. Charts of all patients
      admitted from October 1995 to November 1996 under the age of 9 were reviewed for
      use of INM. Twelve patients had INM used at some point during their
      hospitalization. Our study covers this group, with each child acting as his/her
      own control. Pain and response to medication during wound cleansing was assessed
      by the nursing staff as documented in the patient's nursing assessment. Nursing
      documentation indicated that patient response was positive regarding the use of
      INM with intravenous and/or oral pain medication.

PMID- 11227688
TI  - Marjolin's ulcer of the scalp: report of 5 cases and review of the literature.
AB  - The formation of neoplastic changes in the scar tissue of chronically ulcerating
      wounds is a well-known process. This condition is most commonly seen after the
      postburn scars, but it may be seen after many kinds of scars. The term
      "Marjolin's ulcer" is used to describe this type of carcinoma. Although many
      different cell types can be seen in these lesions, the most commonly seen is
      squamous cell carcinoma. Squamous cell carcinomas resulting from the Marjolin's
      ulcer have a much greater tendency to metastasize than squamous cell carcinomas
      resulting from the other causes. Confusion continues about the precise
      pathophysiology of this lesion and the clinical behavior of this neoplasm, and
      the mortality and morbidity rates are also conflicting. As would be expected,
      there is a wide variety of suggested treatment protocols for this disease. This
      article, through case reports and review of the literature, offers criteria for
      the treatment of the Marjolin's ulcers that arise on the scalp, which is an
      uncommon site.

PMID- 11227689
TI  - A hazard of home oxygen therapy.
AB  - Although it is generally safe, there are morbidities associated with home oxygen
      use. Experience in our burn unit led to an analysis of burn complications from
      this therapy. A retrospective review of records during a 12-year period
      identified 23 patients with burns associated with home oxygen use. Average age of
      the patients was 70 years, with chronic obstructive pulmonary disease the most
      prevalent indication for use. Concomitant cigarette smoking was the most common
      inciting mechanism of the burns (70%). Average burn size was 3.9% of total body
      surface area. Eleven patients presented in the first 10 years of the study
      period, whereas 12 presented in the last 2 years. We have seen a rise in injuries
      with the use of home oxygen. The absolute number of injuries sustained is
      unknown, because many are likely unreported. To decrease the morbidity and costs
      associated with these injuries, the need for continuing safety education is
      apparent.

PMID- 11227690
TI  - The reduction of itch during burn wound healing.
AB  - The purpose of this study was to find a method to reduce the itch experienced by
      patients who have sustained burn injuries, by using and comparing the
      effectiveness of 2 shower and bath oils. One product contained liquid paraffin
      with 5% colloidal oatmeal and the other contained liquid paraffin. The study was
      carried out in the Adult Burns Unit, Royal Brisbane Hospital (RBH), Brisbane. It
      was conducted during a 10-month period from July 1998 until April 1999. Thirty
      five acute burns patients participated in an assessor-blind clinical trial.
      Patients were asked twice daily to rate their discomfort from itch and pain. The
      amount of antihistamine requested by each patient was totalled daily. Analysis of
      data supplied by patients showed that the group using the product with colloidal
      oatmeal reported significantly less itch and requested significantly less
      antihistamine than those using the oil containing liquid paraffin.

PMID- 11227691
TI  - Music therapy for assistance with pain and anxiety management in burn treatment.
AB  - The management of pain is one of the primary issues in burn care. Pain is not
      only a physiologic experience, but a psychological one as well. With this in
      mind, the treatment of burned patients must incorporate a holistic view of pain
      management and healing. Cognitive, behavioral, and pharmacologic interventions
      all have a role in pain management. Studies, as well as clinical experience, have
      shown that musical intervention has been helpful in assisting patients with pain
      management in a variety of medical settings. Music is an element of normal life
      that can be easily adapted for the needs of individual patients and their current
      environment while providing a means for self expression and for normalizing the
      environment. This article examines the rationale for using music therapy with
      burned patients, describes several protocols that have been adapted to meet the
      specific needs of burned patients, and summarizes our preliminary findings, which
      demonstrate significant response to music therapy protocols employed on our
      patients.

PMID- 11227692
TI  - Melanocyte-conditioned medium stimulates while melanocyte/keratinocyte contact
      inhibits keratinocyte proliferation.
AB  - The interaction between melanocytes and keratinocytes in epidermal tissue suggest
      a bidirectional interchange between these two cell types. Although keratinocytes
      appear to affect melanocyte function, there are no reported effects of
      melanocytes on keratinocytes. Using cell strains, we examined the effect of
      melanocytes on keratinocyte proliferation. Two conditioned medium techniques were
      used: one was a co-culture system, where both cell types, grown on separate
      surfaces shared a common volume of medium. The second was simply feeding
      keratinocytes melanocyte-conditioned medium. Mixed cultures (both cell types
      together in a monolayer) where also studied. Our results showed that melanocyte
      conditioned medium and melanocytes in co-culture significantly stimulated
      keratinocyte proliferation as measured by bromodeoxyuridine incorporation assay.
      However, growth of both cell types together in culture did not affect the growth
      rate of either cell type. Our results showed that cultured human melanocytes
      produce one or more soluble factors that stimulate the growth of cultured
      keratinocytes.

PMID- 11227693
TI  - Assistive devices in the rehabilitation on patients with electrical burns--three
      case reports.
AB  - Limb amputation is a devastating sequela in patients with high-voltage electrical
      injuries, which may result in permanent disability. It is vital for
      rehabilitation professionals to assist patients with amputations to maximize
      their residual function. This can be done using a myriad of therapeutic
      adaptation methods such as orthotics, prosthetics, and assistive devices so that
      an optimal performance in daily activities can be achieved. This article
      describes how 3 patients, after electrical trauma with various levels of
      amputation, benefited from customized assistive devices, which are simple but
      effective. Patients' functioning in self-care, home, and work activities was
      improved. This, in turn, led to an enhanced quality of life. In addition,
      guidelines for fabrication of assistive devices are formulated.

PMID- 11227694
TI  - A 10-year experience with toxic epidermal necrolysis.

PMID- 11227695
TI  - The consistency of ploidy analysis for granulosa cells at different stages of
      development.

PMID- 11227696
TI  - Role of providers in ART success.

PMID- 11227697
TI  - Transcripts from testicular sperm as predictors of sperm presence in the
      testicle.

PMID- 11227699
TI  - Arthroscopic treatment of posterior impingement of the elbow in athletes.
AB  - Arthroscopic treatment of posterior impingement of the elbow in athletes
      consistently can improve comfort and function. Arthroscopic treatment is
      particularly valuable because of increased intra-articular visualization of the
      anterior and posterior compartments and diminished soft tissue trauma.
      Arthroscopic visualization also can help the surgeon assess small pathologic
      changes in joint congruity seen in subtle forms of ligamentous instability, which
      are often symptomatic in high-demand athletes. Treatment of these subtle
      instabilities can be individualized to the athlete. Most athletes are able to
      return to the same level of their sport after arthroscopic surgery for posterior
      impingement of the elbow. In certain athletes, however, depending on the position
      played, reoperation rates are high, and return rates to the same level of
      competition can be less than in other athletes with posterior impingement of the
      elbow. Patient selection, technical expertise, and familiarity with open and
      arthroscopic elbow surgery are all criteria for success.

PMID- 11227698
TI  - Osteochondritis dissecans of the elbow.
AB  - Osteochondritis dissecans of the elbow remains a difficult problem to manage in
      the young athlete. Though the etiology is unclear, a definite association between
      overuse with repetitive microtraumatic insult and OCD has been established. Early
      detection and appropriate treatment can provide the best chance for preventing an
      unfavorable outcome. In many cases, conservative treatment regimens will provide
      complete resolution of symptoms, return of function, and full recovery, including
      return to sports participation. Surgical indications should be recognized,
      however, and surgical management carried out when warranted. Most authors treat
      unstable lesions primarily by excision of the fragment, accompanied by drilling
      or burring of the base of the lesion. Symptoms usually improve significantly, but
      approximately half of all patients will continue to experience chronic pain or
      limitation of elbow motion, highlighting the significance and severity of OCD of
      the elbow.

PMID- 11227700
TI  - Arthrofibrosis and complications in arthroscopy of the elbow.
AB  - The authors offer concise procedural advice for arthroscopic treatment of flexion
      contractures of the elbow, bracketed by indications for treatment and
      recommendations regarding postoperative complications.

PMID- 11227701
TI  - Scapholunate instability in athletes.
AB  - Sports medicine practitioners must be sensitive to even the smallest injuries
      that affect athletes. Often, less severe ligament injuries go undetected.
      Scapholunate dissociation is often overlooked in this manner. The authors provide
      an overview of presentation, diagnosis, and nonoperative and operative treatments
      of this condition.

PMID- 11227702
TI  - Arthroscopic capsulodesis of the lunotriquetral joint.
AB  - A case series consisting of 20 consecutive patients with persistent ulnar-sided
      mechanical wrist pain, lunotriquetral interosseous (LTIOL) ligament tears
      resulting in joint incongruity and increased laxity, and traumatic triangular
      fibrocartilage complex (TFCC) tears was reviewed. Each patient underwent an
      arthroscopic reduction and internal fixation (ARIF) of the lunotriquetral joint,
      arthroscopic disk-carpal (disklunate-ulnocapitate-disktriquetral, DL-UC-DT)
      ligament plication, and TFCC repair or debridement. There were 12 right wrists
      and 8 left wrists, of which 12 were dominant. The mean patient age was 33 years;
      7 patients had workers' compensation claims and 2 had legal claims. Fourteen
      patients recalled a specific injury mechanism, such as hyperextension or
      rotation. The accompanying traumatic TFCC tears were peripheral in 15 and linear
      radial in 6 patients (one patient had concomitant peripheral and radial linear
      tears), and in 6 cases, the palmar ulnocarpal extrinsic ligaments were partially
      torn. The mean preoperative modified Mayo Wrist Score was 50, and at a mean of
      3.1 years after surgery, the score had increased to 88. There were 13 excellent,
      5 good, and 2 fair results. Four patients had complications, including transient
      tenderness along the extensor carpi ulnaris and persistent neuritis of a dorsal
      branch of the ulnar nerve. Overall wrist comfort and function, as indicated by
      the modified Mayo Wrist Scores, improved after arthroscopic stabilization of
      ulnar-sided wrist injuries (pinning of the lunotriquetral joint, disk-carpal
      ligament plication, and TFCC repair or debridement).

PMID- 11227703
TI  - Triangular fibrocartilage complex tears in the athlete.
AB  - The treatment of triangular fibrocartilage tears in the athlete presents more of
      a rehabilitation challenge than a surgical technique challenge. The
      rehabilitation regimen is a function of the sport. Although injuries to the
      shoulder and knee can be career ending, injuries to the TFCC usually, but not
      always, can be treated successfully.

PMID- 11227704
TI  - Carpal fractures in athletes.
AB  - A review of the literature shows that 3% to 9% of all athletic injuries occur to
      the hand or wrist. Also, hand and wrist injuries are more common in pubescent and
      adolescent athletes than adults. Although knee and shoulder injuries are more
      common athletic injuries, an injury to the hand or wrist significantly can impair
      the athlete's ability to throw or catch a ball, or swing a bat or racquet. A
      college football player trains year round for just 11 or 12 hours of playing
      time. An athletic injury that occurs during the season can have profound
      consequences for the athlete's career and emotions. When defining a management
      plan for a particular wrist athletic injury, the time to heal the injury and the
      time to rehabilitate fully must be considered. The athlete must be informed fully
      of the length of recovery. The continued advancement of fixation methods and
      techniques are diminishing fracture morbidity considerably. Small-cannulated
      compression screws that provide rigid fixation can be inserted with decreased
      surgical dissection, thus preserving critical vascular supply and promoting
      accelerated healing and earlier rehabilitation. The arthroscope as a valuable
      adjunct in the management of wrist fractures was virtually unheard of years ago,
      but is now common. The ability to arthroscopically guide a cannulated compression
      screw to stabilize a scaphoid fracture without a formal open volar approach can
      reduce surgical morbidity significantly and allow the athlete to return to
      competition more quickly. Mechanisms of injury that cause osseous fractures of
      the wrist are fairly high energy. A high index of suspicion for associated soft
      tissue injuries should be kept in mind when fractures of the wrist are
      identified. The wrist is composed of eight carpal bones tightly interwoven with
      each other by intrinsic and extrinsic wrist ligaments. The management of carpal
      fractures depends on prompt diagnosis, stable and anatomic alignment of the
      involved carpal bone, protective immobilization of the injury, and thorough
      rehabilitation. Displaced fractures of the hook of the hamate, trapezial ridge
      fractures, and comminuted pisiform fractures are managed best by early excision
      to promote uncomplicated recovery and early return to sport. For most athletes,
      return to competition can be expedited safely with the use of padded gloves and
      custom playing splints or casts. The sports medicine physician always must put
      the athlete's safety first when deciding the appropriate time for return to
      competition.

PMID- 11227705
TI  - Radius fractures in the athlete.
AB  - With prompt and accurate diagnosis, a stable and anatomic distal radius fracture
      reduction, the detection and treatment of any associated intraarticular injuries
      with the use of wrist arthroscopy, and an early, comprehensive rehabilitation
      program, one usually can expect a favorable outcome. The treating physician never
      should compromise these basic principles solely for the sake of a speedy return
      to sports at the behest of the coach, the athlete, or his family. This could
      result in a less-than-favorable recovery, and a possible permanent loss of
      athletic skills.

PMID- 11227706
TI  - Nerve injuries of the elbow, wrist, and hand in athletes.
AB  - Upper extremity compression neuropathies are fairly rare in athletes. Initially,
      most can be managed conservatively. These conditions can follow direct contusion
      of the tissues that overlay these peripheral nerves or can result from vigorous,
      repetitive, athletic activity leading to tissue swelling and ischemia with nerve
      compression symptoms. A complete history and physical examination, including a
      neurologic examination, should be paramount when treating athletes with upper
      extremity injuries. Early diagnosis and treatment with conservative measures such
      as splinting, rest, activity modification, and medications can afford the athlete
      an earlier return to sports. Surgery can be employed when conservative treatment
      fails and a specific diagnosis has been ascertained.

PMID- 11227707
TI  - Valgus instability of the elbow in athletes.
AB  - Valgus instability of the elbow in athletes is uncommon among athletes in
      general, but has a higher incidence in individuals who throw repetitively. When
      valgus overload injury results in disabling symptoms for the athlete, surgical
      reconstruction of the anterior band of the ulnar collateral ligament may be
      indicated. This procedure has been successful in getting athletes back to
      premorbid levels of competition. The authors provide a comprehensive review of
      valgus instability of the elbow and offer their preferred method of treatment.

PMID- 11227708
TI  - Posterolateral rotatory instability of the elbow.
AB  - Since its original description by O'Driscoll in 1991, PLRI is becoming
      increasingly recognized as a significant cause of elbow pathology. It is well
      documented that this problem results from an insufficiency of the radial
      ulnohumeral ligament and its related lateral structures, and that this
      insufficiency is usually the result of elbow trauma. Diagnosis has improved with
      the introduction of the PLRI test to identify the instability and advancing MR
      imaging capabilities of illustrating the injury. Whereas open reconstruction was
      previously the only definitive treatment, improving arthroscopic techniques
      provide a satisfactory alternative in stabilizing the elbow.

PMID- 11227709
TI  - Fracture dislocations of the elbow in athletes.
AB  - Elbow dislocations can result in extensive injury to the supporting structures of
      the elbow joint. Principles of treatment include prompt reduction of the
      dislocation and treatment of associated fractures. The goal is to restore joint
      stability and to allow for early mobility. Most simple dislocations are stable
      after closed reduction with early mobility that can lead to anatomic and
      functional restoration. When stability is compromised, as with many complex
      dislocations, further stabilization with ligament repair, reconstruction, and
      fracture fixation also can lead to satisfactory results. The prognosis following
      complex dislocations is more guarded in the athlete, and depends on anatomic
      restoration and initiation of early motion.

PMID- 11227710
TI  - Epicondylitis in the athlete.
AB  - Epicondylitis plagues a significant proportion of athletes and can result in
      prolonged symptoms and suboptimal athletic performance. The diagnosis can be
      confused with many other pathologic entities affecting the elbow, some of which
      can occur concurrently. Most patients will respond favorably to a well-guided
      nonsurgical treatment protocol. A minority of patients will have persistent
      problems and will require surgical intervention that can relieve pain effectively
      and return patients to their preinjury level of activity.

PMID- 11227711
TI  - Nerve entrapment in athletes.
AB  - Nerve entrapment syndromes can occur in athletes. The repetitive and vigorous use
      or overuse of the upper extremity makes the athlete particularly vulnerable to
      disorders of peripheral nerves. Understanding the clinical signs and symptoms is
      essential to treatment. The pertinent anatomy, clinical presentation, treatment,
      and rehabilitation necessary for return to sports for various nerve entrapments
      have been described. This should enable the physician caring for the athlete to
      help prevent injury and to guide appropriate treatment, if intervention becomes
      necessary.

PMID- 11227712
TI  - [Left ventricular reconstruction after excision of a large fibroma].
AB  - The authors report the case of a 15 year old boy with a large left ventricular
      fibroma discovered after a series of syncopal episodes due to obstruction to
      ejection. The first attempt to remove the fibroma in Columbia was only partially
      successful. In view of the risk of death associated with this type of tumour, it
      was decided to offer the patient complete excision after a full morphological and
      functional evaluation of myocardial function and the consequences of the tumour
      on mitral valve function and on the coronary circulation. The operation was
      performed under cardiopulmonary bypass and aortic clamping by conventional
      surgery, associated with reconstruction of the cardiac free wall with a large
      patch of autologous pericardium which was necessary to avoid cardiac
      transplantation, the ultimate sanction in this indication.

PMID- 11227713
TI  - [Implantation of long coronary stents. Immediate and long-term results].
AB  - There have been few clinical reports of the long term results of implantation of
      long coronary stents. The authors performed a retrospective study of the long
      term results of 213 implantations of long stents (20 mm long) in 202 patients.
      These results were compared with those obtained in patients implanted with short
      stents (< 20 mm long) during the same period (630 implantations in 530 patients).
      The angiographic and clinical success rates were respectively 96.5 and 95.4% in
      the "long stent" group compared with 97.2 and 94.9% in the "short stent" group.
      In the "long stent" group, at 6, 12 and 24 months (follow-up, the cumulative
      incidence of nex revascularisation procedures of the target lesion were 9.8, 14.3
      and 20.6% respectively, whereas the cumulative incidences of major cardiac events
      (mortality, infarction, angina, coronary bypass surgery and angioplasty) for the
      same periods were 12.7, 21.1 and 40% respectively. There was no significant
      differences compared with the "short stent" group concerning all these events.
      However, after 6 months, there was a tendency for more major cardiac events and
      for more new revascularisation procedures of the target lesion in the "long
      stent" group. In multivariate analysis, the independent predictive factors for
      major cardiac events were: a Jeopardy score > 6 (p = 0.002), and the complex
      nature of the lesion (B2 or C) (p = 0.045), whereas the independant risk factors
      for a new revascularisation procedure of the target lesion were: minimal luminal
      diameter after the procedure, a Jeopardy score > 6, complex lesions, diabetes and
      the reference diameter of the stented arterial segment. The authors conclude that
      although the length of the stent as such is not a long term predictive factor,
      the complexity of the lesion and the severity of the coronary disease which are
      more common in the "long stent" group explain the non-significant tendency for a
      higher incidence of major cardiac events in this group.

PMID- 11227714
TI  - [Immediate revascularization by angioplasty and coronary stents in patients over
      age 80 with myocardial infarction].
AB  - The aim of this study was to assess the results of revascularisation by
      angioplasty and stenting in octogenarians in the acute phase of myocardial
      infarction. One hundred and four patients over 80 years of age were identified
      between January 1995 and April 1995 out of 906 patients admitted within 24 hours
      of the onset of myocardial infarction. The average age was 85 +/- 4 years with a
      female predominance (63.4%) and a high incidence of cardiogenic shock (28.8%).
      Ninety eight patients underwent angioplasty with coronary stenting in 81 patients
      (82.6%) within 39 +/- 35 min of hospital admission. A primary success was
      obtained in 96% of cases with restitution of TIMI 3 flow in 83.6% of cases.
      Hospital mortality was 26.5%, highly influenced by the presence of cardiogenic
      shock (60.7% versus 12.8% without shock). Univariate analysis showed cardiogenic
      shock (p < 0.0001) and ejection fraction (p = 0.009) to be predictive of
      mortality, and a tendency in favour of TIMI 3 flow (p = 0.07) and stent
      implantation (p = 0.09). Complications were rare: 1% of minor cerebrovascular
      accidents and 4% of vascular complications. There were no cases of emergency
      bypass surgery and only one patient had a recurrence of ischaemia at 30 days. The
      authors conclude that the results at 1 month in a high risk group of
      octogenarians seem to be in favour of an invasive management with coronary
      stenting in the acute phase of myocardial infarction.

PMID- 11227715
TI  - [Transluminal coronary angioplasty performed in patients with single vessel
      disease of the right coronary artery disease. Long-term results].
AB  - The patients who have only single vessel disease of the right coronary artery
      have an excellent prognosis, unaffected by surgery. The object of this study was
      to evaluate the long-term prognosis of these patients after transluminal coronary
      angioplasty. The criteria of analysis were survival, anginal symptoms, quality of
      life and ergometric parameters. Two hundred and forty eight patients with an
      isolated lesion of the right coronary artery who underwent angioplasty were
      reassessed 39.6 +/- 22 months after angioplasty. The primary success rate was
      89.9% with 5.2% of severe complications during the hospital period (myocardial
      infarction, bypass surgery, coronary angiography +/- angioplasty). The actuarial
      global and cardiac survival rates at 7 years were 88.4 and 96.2% respectively
      with no difference between the success and failure groups. The eight
      cardiovascular deaths and thirteen myocardial infarctions which were observed in
      the long-term were all in the successful angioplasty group. From the symptomatic
      viewpoint, 76% of the population became asymptomatic. The same results were
      observed in terms of quality of life with 58% of patients estimating it to be
      good in correlation with anginal status. The comparison of ergometric tests
      showed a significant gain in performance in 67% of patients. The authors conclude
      that the results suggest that angioplasty in single vessel disease of the right
      coronary artery provides a significant symptomatic and ergometric benefit but
      that it is impossible to assess the eventual benefits in terms of survival which
      would have needed a group of similar patients assessed under anti-ischaemic
      treatment and taking into consideration the recent innovations (stents, statins).

PMID- 11227716
TI  - [Randomized comparison of 4F and 6F catheters for diagnostic coronary
      angiographies via the femoral approach].
AB  - The use of 6F catheters has been validated for coronary angiography. The use of
      small-caliber catheters is a more recent development. The aim of this study was
      to assess the feasibility, the cost and complications of coronary angiography
      using the femoral approach with 4F catheters. The authors undertook a randomized
      prospective study of 4F Care Infiniti catheters (N = 100) and 6F Spertorque Plus
      catheters (N = 100) in hospitalised patients. Criteria of non-inclusion were
      valvular pathology, acute myocardial infarction, aorto-coronary bypass or aorto
      femoral bypass procedures. No statistical difference was observed between the two
      groups with respect to feasibility, to duration of the procedure, or of
      irradiation or to cost. The quality of the angiograms was good except in one
      patient in the 4F group; 4 patients in the 6F group required a 4F catheter to
      complete their examination. Left ventricular catheterisation was more difficult
      with 4F catheters (p = 0.016). Use of 4F catheters was associated with injection
      of significantly less contrast (p = 0.00007), reduced the duration of compression
      (p < 10(-6)) and its complications (p = 0.004). The authors conclude that 4F
      catheters are safe and well tolerated. They are associated with less patient
      morbidity, without any loss in quality of the angiogrammes. Other studies in
      valvular heart disease and after coronary bypass surgery should lead to the
      generalisation of their use in all coronary patients.

PMID- 11227717
TI  - [Improved left ventricular endocardial detection by a first generation contrast
      agent. Effect of dose].
AB  - The study of global and segmental left ventricular function forms part of every
      echocardiographic examination. However, this is only possible when the
      endocardial borders are well identified. The authors report the results of a
      study with Albunex, a first generation contrast agent used by intravenous
      injection. The object of this study was to assess the efficacy of Albunex in
      improving left ventricular endocardial detection compared with standard
      transthoracic echocardiography (TTE) and the dose-effect relationship. Forty-one
      patients were included prospectively at two cardiological hospital centres
      between 1995 and 1997, before the development of second harmonic imaging. Two
      patients were excluded from the study. Each patient underwent transthoracic
      echocardiography in the fundamental mode with an apical four-chamber view. The
      following procedure was adopted: 1) standard examination, 2) low dose Albunex
      (0.1 mg/Kg) injected via a peripheral vein, 3) high dose Albunex (0.2 mg/Kg)
      injected via a peripheral vein, 4) low dose Albunex injected via a central vein,
      5) high dose Albunex injected via a central vein. The analysis of results was
      performed by two independent observers and showed that Albunex improved
      endocardial detection (p < 0.005); this detection was significantly better with
      high doses of Albunex and with central vein injection (p < 0.005); the septal
      border was better visualised than the lateral wall endocardium (p < 0.005) but
      the improvement in endocardial detection was greater for the lateral wall (p <
      0.005). No complications were observed during the procedure. The authors conclude
      that Albunex improves left ventricular endocardial detection. This benefit is
      mainly due to improved lateral wall detection, and increases with higher doses of
      the contrast agent.

PMID- 11227718
TI  - [Determinants of survival after implantation of an automatic defibrillator.
      Report of 127 patients].
AB  - The authors present a retrospective and longitudinal study of the predictive
      factors of mortality in patients having an implanted automatic defibrillator. The
      population comprised 127 patients implanted between September 1988 and September
      1997. There were 107 men with a mean age of 57.7 +/- 13 years. The left
      ventricular ejection fraction was 39.3%. The proportion of coronary patients was
      68%; 20% of patients had atrial fibrillation and 5% were in Class III of the NYHA
      classification. The indications were: resuscitated cardiac arrest (N = 56) and
      poorly tolerated ventricular tachycardia (N = 71). The follow-up period was 30 +/
      25 months. There were 23 early and 10 late complications. Seventy-two patients
      had received an electric shock; 57 had an appropriate shock. There were 23
      arrhythmic storms (ventricular arrhythmia requiring at least 2 shocks in less
      than 24 hours) in 17 patients. The operative mortality was 1.1%; at 1 year, the
      global survival was 93.9 +/- 2.2%; cardiac survival was 94.7 +/- 2.1%; survival
      without sudden death was 98.3 +/- 1.2%. Multivariate analysis isolated predictive
      factors for mortality; atrial fibrillation was predictive for global mortality;
      an ejection fraction < 30% and the fact of having received an appropriate shock
      were predictive of cardiac mortality; and an arrhythmic storm was predictive of
      sudden death.

PMID- 11227719
TI  - [Predictive value of induction of atrial flutter or fibrillation in paroxysmal
      junctional tachycardia].
AB  - The association of different types of tachycardia in a given patient is a well
      known phenomenon and the development of ablative methods rises hopes that
      treatment of one of them may suppress the others. The aim of this study was to
      determine the significance of induction of atrial flutter or fibrillation (AF)
      during electrophysiological investigation of patients investigated for paroxysmal
      junctional tachycardia. The initial population of 500 patients was limited to 485
      patients, aged 12 to 86, with a normal intercritical ECG and without a Wolff
      Parkinson-White syndrome, who underwent electrophysiological investigation for
      junctional tachycardias since 1978 and in whom the tachycardia could be
      reproduced. The study was performed by the endocavitary approach in 262 cases and
      by the transoesophageal approach in 213 cases with a similar protocol, programmed
      atrial stimulation with 1 and 2 extrastimuli under basal conditions, eventually
      completed by the repetition of the protocol with low doses of isoproterenol. The
      electrophysiological study showed that the tachycardia involved a latent bundle
      of Kent in 103 cases, a double nodal pathway in 343 cases or another circuit in
      39 cases. During this study, sustained AF was induced in 66 cases (13.5%) with a
      similar incidence in Kent bundles (14.5%), intranodal reentry (11%) and other
      forms of reentry (11%). During follow-up, ranging from 6 months to 10 years, 7
      patients with induced AF and 9 without inducible tachycardia, developed permanent
      AF. The occurrence of the arrhythmia was significantly correlated with the
      mechanism of reentry (latent Kent 8/103 cases, intranodal reentry 8/343 cases, p
      < 0.05), and with the induction of the same arrhythmia by oesophageal
      investigation alone (p < 0.001). The initiation of the arrhythmia by endocavitary
      stimulation did not seem to have any positive predictive value. In conclusion,
      the induction of atrial flutter or fibrillation during investigation of a subject
      with paroxysmal junctional tachycardia without a patent Wolff-Parkinson-White
      syndrome, does not seem to be predictive of future development of atrial flutter
      or fibrillation, unless the investigation was undertaken by the oesophageal
      approach.

PMID- 11227720
TI  - [Changes in velocity of left ventricular filling measured by color M-mode during
      dobutamine stress echocardiography].
AB  - Myocardial ischaemia affects left ventricular relaxation. The velocity of
      propagation of rapid left ventricular filling flow (VPF, cm/s) measured by colour
      M-mode is strongly correlated with the haemodynamic constant of left ventricular
      relaxation (Tau). The authors compared the changes in VPF during stress
      echocardiography with Dobutamine in a control group of non-coronary patients
      (Group 1, N = 12) and a group of coronary patients (Group 2, N = 29). Coronary
      angiography was performed in all patients. The basal VPF were similar in both
      groups (Group 1: 68.3 +/- 22.7 cm/s vs Group 2: 66.2 +/- 23.1 cm/s, NS). The VPF
      at the peak of dobutamine infusion were significantly different from the values
      observed under basal conditions in Group 1 (105.1 +/- 25.0 cm/s, p < 0.001)
      whereas this difference was not significant in Group 2 (67.4 +/- 19.3 cm/s, NS).
      There were significant differences between the two groups for peak values (p <
      0.001) and for percentage variation of VPF (peak-basal value/basal value) with
      respect to the basal values (Group 1: 63 +/- 43% vs Group 2: 9 +/- 39%, p <
      0.01). A percentage variation of VPF < 25% (Group 1: 3/12 patients and Group 2:
      23/29 patients) allows detection of coronary artery disease with a sensitivity of
      79% and a specificity of 75%. During Dobutamine infusion, the velocity of
      propagation of left ventricular filling flow increases less in coronary patients
      than in non-coronary patients. The study of this quantitative parameter of left
      ventricular relaxation seems to be a valuable tool for detecting the presence of
      coronary artery disease during stress echocardiography.

PMID- 11227721
TI  - [Utilization of heart rate at the ventilatory threshold for the prescription of
      intensity of exercise training in cardiac failure].
AB  - Physical exercise is a treatment for cardiac failure but a large range of
      intensities of exercise is proposed. The aims of this study were to determine the
      range of intensities of effort used and to individualize the intensities used.
      Thirty patients with stable cardiac failure (NYHA Classes II-III, age: 53 +/- 2.1
      years, ejection fraction: 31 +/- 1.4%) underwent a cardiorespiratory exercise
      stress test before and after individualized training at the ventilatory
      threshold. However, before and after the training period, standard methods of
      calculation of the intensities at the ventilatory threshold showed individual
      differences greater than +/- 2 standard deviations, indicating different
      metabolic stimulations. After the individualized training programme, peak oxygen
      consumption on exercise (1679 +/- 100 vs 1487 +/- 89 ml.min-1, p = 0.0001) and at
      ventilatory threshold increased (1365 +/- 85 vs 1133 +/- 65 ml.min-1, p =
      0.0001), the ventilatory threshold/peak exercise ratio increased (81.2 +/- 1.3 vs
      76.7 +/- 1.4%, p = 0.0008), and there was a decrease in heart and ventilatory
      rates at submaximal metabolic levels (p = 0.0001). The authors conclude that
      protocols using intensity of effort at the ventilatory threshold give similar
      results with respect to improvement of aerobic capacity as other methods of
      indirect calculation, based on maximal heart rate of oxygen consumption. The
      value of this particular method lies in the adequation between aerobic capacity
      of the patient and the intensity of training. The results obtained attain the
      physiopathological aims of rehabilitation.

PMID- 11227722
TI  - [Idiopathic orthostatic tachycardia. Etiology, diagnosis and treatment].
AB  - For nearly a century, physicians have been aware of a syndrome consisting of a
      relatively stereotyped presentation, usually in young patients, who complain of
      fatigue, malaise and effort intolerance, sometimes of trembling and weakness of
      the lower limbs. This is associated with an excessive tachycardia in the
      orthostatic position. This syndrome has recently been called idiopathic
      orthostatic tachycardia. The tilt test has enabled "quantification" of normal
      responses. Patients complaining of the symptoms described above and which, during
      the first minutes of orthostatism, increase their heart rates by more than 30
      beats per minute or attain a rate of at least 110/min, are considered to be
      suffering from this syndrome. The physiopathology is not clear but, globally,
      there seems to be two sub-groups, the first considered to be a partial
      dysautonomic disorder and the second, the result of hypersensitivity of the beta
      receptors. Besides the tilt test, the diagnosis can also be presumed after an
      excessive tachycardia response to an intravenous infusion of 1 microgram/min of
      isoprenaline. The treatment of these patients is uncertain as there is no single
      approach which is always effective. In addition to "simple" but essential advice,
      a number of drugs may be used although there is no means of predicting the
      efficacy of the result in a given patient. A major principle should be
      emphasised: ablation of the sinus node for inappropriate tachycardia may
      eliminate the only compensatory mechanism of autonomic dystonia and make the
      patients even more symptomatic than they were.

PMID- 11227723
TI  - [Myocardial metabolism abnormalities during ischemia and reperfusion].
AB  - Normal cardiac function requires adequate oxygen and substrate (fatty acids,
      glucose lactate) supply for the energetic requirements of the myocardium.
      Ischaemia induces abnormalities in the production and excretion of products of
      myocardial metabolism. During ischaemia, the equilibrium which exists during
      aerobic respiration between the beta-oxidation of fatty acids and carbohydrates
      and which generates ATP is disturbed. Pyruvate oxidation and beta-oxidation of
      fatty acids decrease, and ATP is mainly produced by anaerobic glycolysis. Under
      these conditions, intracellular glycogen is mobilised, the lactate and protons
      accumulate in the cardiomyocyte. If reperfusion occurs before irreversible
      lesions are produced, then functional recovery is possible and is mostly
      dependant on the type of energetic substrate available. Circulating fatty acids
      are produced in large quantities after ischaemia: their beta-oxidation, which is
      then the principal source of ATP, may contribute to the aggravation of
      contractile dysfunction during reperfusion and accentuate or generate
      arrhythmias. The decoupling between acceleration of anaerobic glycolysis and the
      defect of pyruvirate oxidation (inhibition of pyruvirate dehydrogenase)
      participate in a significant fashion to the accumulation of protons. Rapid
      correction of intracellular acidosis during reperfusion by activation of the
      Na+/H+ exchanger, coupled with the accumulation of intracellular Na+ induces a
      deleterious calcium overload via the Na+/Ca++ exchanger. These different aspects
      of intracellular metabolism constitute pharmacological targets for the
      development of future cardio-protective agents.

PMID- 11227724
TI  - [Aneurysm of the interatrial septum and right-to-left shunt during biventricular
      infarction. Diagnosis by transesophageal echocardiography].
AB  - A right-to-left shunt during infarction with right ventricular extension is a
      rare and recently described complication. It results from opening of a foramen
      ovale due to increased right heart pressures. The authors describe another case
      occurring in a patient with an interatrial septal aneurysm, the diagnosis of
      which was made by transoesophageal echocardiography.

PMID- 11227725
TI  - [Hydatic disease of the heart presenting with pericardial effusion. A case
      report].
AB  - The authors report a rare case of multiple mediastinal hydatid cysts which
      ruptured in a 48 year old man who presented with a pericardial effusion. The
      diagnosis was confirmed by 2D echocardiography, completed by CT scan and magnetic
      resonance imaging. The patient was operated as a semi-emergency and the outcome
      was good. This case underlines the rare pericardial involvement and the severity
      of the complications of cardiac hydatid disease.

PMID- 11227726
TI  - Effect of acute elevation of IGF-I on circulating GH, TSH, insulin, IGF-II and
      IGFBP-3 levels in non-endocrine short stature (NESS).
AB  - It is not clear whether acute and slight elevation of serum IGF-I, which does not
      affect blood glucose levels, modulates circulating GH levels. To clarify this,
      small doses of recombinant human IGF-I (rhIGF-I, 5 microg/kg, i.v.) were
      administered as a bolus to 10 children with non-endocrine short stature (NESS) (5
      males and 5 females, 11.2+/-0.7 yr old) after an overnight fast. Physiological
      saline was administered intravenously to sex- and age-matched NESS controls (5
      males and 5 females, 10.9+/-0.7 yr old). The changes of serum GH, TSH, PRL, IGF
      I, IGF-II, IGFBP-3, T4, T3 and plasma glucose levels after the administration
      were compared to those of the control subjects. Serum IGF-I levels increased
      significantly from 15 to 150 min after injection compared to those in the control
      group. The peak value was observed at 15 min (delta increment, 74.6+/-11.8
      microg/l). At 15 min after the injection, serum insulin was suppressed
      significantly (p<0.05), although plasma glucose levels were not modified
      significantly. Serum TSH showed a significant decrease by rhIGF-I at 15 min and
      60 min, whereas serum T4 and T3 levels were not modified. Serum GH was also
      significantly suppressed at 60 min (p<0.02) and showed a rebound increase at 120
      min (p<0.05). Serum IGFBP-3 levels after rhIGF-I were higher than controls at 90
      min and 150 min. No significant changes of serum PRL, IGF-II, (IGF-I plus IGF
      II)/IGFBP-3 ratios were observed after the IGF-I injection compared to controls.
      These results indicate that circulating IGF-I is a physiological regulator of GH
      secretion in normal children, since the changes of IGF-I after the small doses of
      rhlGF-I administration were within physiological ranges and did not affect plasma
      glucose levels.

PMID- 11227727
TI  - Congenital deficiency of 11beta-hydroxysteroid dehydrogenase (apparent
      mineralocorticoid excess syndrome): diagnostic value of urinary free cortisol and
      cortisone.
AB  - The syndrome of apparent mineralocorticoid excess (AME) is an inherited form of
      hypertension. This disorder results from an inability of the enzyme 11beta
      hydroxysteroid dehydrogenase (11beta-OHSD) to inactivate cortisol to cortisone.
      The diagnosis of AME is usually based on an elevated ratio of cortisol to
      cortisone reduced metabolites in the urine [tetrahydrocortisol plus
      allotetrahydrocortisol to tetrahydrocortisone (THF+alloTHF/THE)]. The principal
      site of "A" ring reduction is the liver, but AME arises from mutation in the gene
      encoding 11beta-OHSD2 in the kidney. We used a gas chromatographic/mass
      spectrometric method to measure the urinary free cortisol (UFF) and free
      cortisone (UFE) in 24 patients affected by the two variants of AME [19 with the
      classical form (type I) and 5 with the mild form called AME type II] in order to
      provide a more reproducible in vivo measure of the renal enzymatic activity. Type
      I patients were divided into two groups: children under 12 and adults. UFF levels
      (microg/24 h) did not differ between under-12 controls and AME type I children
      (mean+/-SD, 9+/-4 and 15+/-12, respectively), but was significantly higher in
      affected adults compared to controls: (62+/-32 vs 29+/-8, p<0.01). No differences
      were found between adult controls and AME type II patients (29+/-8 and 37.0+/-14,
      respectively). UFE was undetectable in 63% of AME type I and significantly lower
      in AME type II (p<0.05). As a consequence UFF/UFE ratio was significantly higher
      in AME type I patients both in children and adults compared to controls (AME
      children: 5.1+/-2.6; normal children: 0.43+/-0.2, p<0.01; AME type I adults:
      17.7+/-19.6; normal adults: 0.54+/-0.3 p<0.01). For AME type II, where UFE was
      detectable in every case, the UFF/UFE ratio was significantly higher than adult
      controls (2.75+/-1.5 vs 0.54+/-0.3, p<0.01). In conclusion, our study indicates
      that UFE and UFF/UFE ratio are sensitive markers of 11beta-OHSD2, directly
      reflecting the activity of the renal isozyme and readily identifying patients
      with AME. The presence of an altered UFF/UFE ratio in both types of AME, although
      with different degree of severity, calls for re-evaluation and the classification
      of AME as a single disorder.

PMID- 11227728
TI  - Clinical relevance of cardiac natriuretic peptides measured by means of
      competitive and non-competitive immunoassay methods in patients with renal
      failure on chronic hemodialysis.
AB  - Increased levels of cardiac natriuretic peptides in patients undergoing
      hemodialysis may be a marker of cardiomyopathy and in consequence may be suitable
      prognostic indicators for the risk of development of cardiac disease. We measured
      plasma levels of ANP, BNP, proANP(1-98) and proBNP(1-76)-related peptides with
      some competitive and non-competitive immunoassay methods in patients with renal
      failure on chronic hemodialysis in order to compare the analytical performances
      of these methods and to evaluate the clinical usefulness of each assay for
      patients with chronic renal failure. ANP and BNP values significantly decreased
      after hemodialysis (on average, ANP by 36% and BNP by 16%); while all proANP and
      proBNP values tended to increase, but only proANP(1-30) (by 14.4%) and Nt-proBNP
      (by 9.5%) significantly. Although significant correlations were found among all
      the circulating levels of cardiac peptides studied, N-terminal pro-peptides
      correlated better among themselves than with ANP and BNP; ANP was only slightly
      correlated with all the other peptides, the only exception being BNP. Only BNP
      levels significantly increased according to the degree of ventricular hypertrophy
      and/or ventricular function in patients with chronic renal failure. The ANP assay
      is preferable in physiological and clinical studies for the rapid changes in
      atrial pre-load. BNP would be more useful in the follow-up of cardiac
      complications in patients with end-stage renal disease on regular hemodialysis.
      The assays of N-terminal proANP(1-98)-and proBNP(1-76)-related peptides proved to
      be of limited use, because they were not able to detect acute changes in pre-load
      during hemodialysis and were less useful than BNP levels as markers of
      ventricular hypertrophy and/or functional cardiac impairment.

PMID- 11227729
TI  - Hormonal regulation of appetite and body mass in patients with advanced prostate
      cancer treated with combined androgen blockade.
AB  - Cachexia is rarely observed in patients with advanced prostate cancer treated
      with combined androgen blockade. Androgens play an important role in the
      regulation of body mass composition and influence the secretion of leptin, the
      appetite regulating hormone. The aim of the study was to assess the influence of
      a combined treatment with nonsteroidal antiandrogen and LH-RH analogue on the
      hormonal regulation of appetite and changes in body mass in patients with
      advanced prostate cancer (Whitmore-Jewett stage D1 or D2). Eighteen patients with
      prostate cancer and 17 healthy subjects matched for age and body mass index were
      included. In all patients serum concentrations of leptin, neuropeptide Y (NPY),
      insulin, testosterone and estradiol were measured before and after four and
      twelve weeks of androgen blockade. Pretreatment serum leptin levels were similar
      in patients with prostate cancer and in the controls. In a multiple regression
      analysis only body mass index and testosterone significantly contributed to the
      variation of plasma leptin. During the treatment body mass and plasma leptin
      significantly increased while NPY decreased. The change of plasma NPY was
      significant only after 4 weeks of therapy. This study shows that the afferent
      regulation of leptin secretion is unchanged in advanced prostate cancer. Androgen
      ablation significantly increases body mass and influences secretion of appetite
      regulating hormones. Testosterone appears to play a significant role in the
      regulation of leptin secretion.

PMID- 11227730
TI  - Administration of glutathione in patients with type 2 diabetes mellitus increases
      the platelet constitutive nitric oxide synthase activity and reduces PAI-1.
AB  - Several studies suggest that nitric oxide (NO) production is impaired in diabetes
      mellitus. Reduced levels of NO could contribute to cardiovascular mortality.
      Furthermore, NO synthesis is impaired in glutathione (GSH)-depleted human
      umbilical vein endothelial cells and GSH is reduced in patients with type 2
      diabetes mellitus (T2DM). We tested the hypothesis that treatment with GSH may
      improve platelet constitutive NO sinthase (cNOS) activity in patients with T2DM.
      Fifteen patients with T2DM underwent a treatment with GSH 600 mg/day i.m. for 10
      days. With respect to the basal values on the 10th day of treatment, the red
      blood cell GSH concentration and platelets cNOS increased (1.4+/-0.1 vs 1.9+/-0.1
      micromol/10(10) RBC, p<0.001 and 0.7+/-0.1 vs 2.9+/-0.2 fmol x min(-1) x 10(-9)
      PLTs, p<0.001, respectively) and the plasma PAI-1 levels diminished (81.4+/-3.7
      vs 68.7+/-4.0 ng/ml, p<0.002). A negative correlation between the cNOS and the
      PAI-1 was found on the basal values. After a wash-out of 30 days the values of
      red blood cell GSH concentration, platelet cNOS activity and PAI-1 Ag returned to
      the basal levels. These data suggest that the administration of GSH, in patients
      with T2DM, is able to improve platelet cNOS activity together with a reduction of
      PAI-1.

PMID- 11227731
TI  - Occult parathyroid carcinoma in a patient with papillary thyroid carcinoma and
      Hashimoto's thyroiditis.
AB  - A 47-year-old female patient with a previous history of right thyroid lobectomy
      was admitted to the hospital because of a 3 cm nodule in the thyroid gland.
      Hormonal evaluation showed subclinical hypothyroidism with serum levels of
      thyroid stimulating hormone slightly elevated to 4.4 microg/dl (normal: 0.4-4
      microg/dl). Thyroid ultrasound showed diffuse irregularity of the gland and the
      presence of a solitary nodule (30x18 mm in diameter) localized in the left lobe.
      A fine needle aspiration biopsy was performed. Cytological analysis revealed
      papillary thyroid carcinoma and Hashimoto's thyroiditis. Total thyroidectomy was
      performed. During the operation, two of the parathyroid glands were detected to
      be hyperplastic. Histopathological examination of the thyroid and parathyroid
      glands revealed Hashimoto's thyroiditis with papillary thyroid carcinoma and
      synchronous carcinoma of the parathyroid gland. To our knowledge, this
      association of occult parathyroid carcinoma in a patient with papillary thyroid
      carcinoma and Hashimoto's thyroiditis has not been reported in the literature.
      Given the high prevalence of autoimmune diseases in elderly women, a random
      occurrence of this triad represents the most likely explanation.

PMID- 11227732
TI  - Pituitary abscess presenting with cranial nerve paresis. Case report and review
      of literature.
AB  - Non-adenomatosus lesions of the pituitary represent a small part of the
      intrasellar processes and they have heterogeneous presentation. Making a precise
      diagnosis is of great importance, as it may lead to more efficient management. A
      65-year-old man was admitted to the hospital because of headache and right
      cranial nerve III palsy. Basic laboratory work-up was normal whereas
      endocrinological assessment revealed hypopituitarism without diabetes insipidus.
      Plain radiography showed an enlarged sella and frontal and paranasal sinusitis.
      Computed tomography (CT) and magnetic resonance imaging (MRI) of the sella
      revealed an intrasellar lesion with extension to the sphenoid and cavernous
      sinuses as well as the suprasellar region, exerting pressure on the optic chiasm.
      On T1-weighted images the mass had a low-intensity signal with a smooth enhancing
      rim with bright signal. Given the presence of multiple sinusitis and imaging
      characteristics a pre-operative diagnosis of pituitary abscess was made. The
      patient was operated via transphenoidal route and purulent material was drained
      out. Cultures of the material were positive for Staphylococcus aureus.
      Antibiotics as well as cortisol replacement therapy were given. Three months
      later hypopituitarism persisted but there was significant improvement in the
      neurological findings. We report a case of an unusual presentation of a pituitary
      abscess. High index of suspicion, the presence of associated conditions such as
      pituitary tumors, meningitis or sinusitis, as well as diabetes insipidus and
      specific imaging features are the main diagnostic clues. Pre-operative diagnosis,
      which will lead to prompt antibiotic therapy and transphenoidal drainage, can
      decrease high mortality and morbidity associated with this disease.

PMID- 11227733
TI  - RET proto-oncogene mutation in a mixed medullary-follicular thyroid carcinoma.
AB  - A case of a patient with an uncommon thyroid carcinoma, showing histological and
      immunohistochemical features of both follicular and parafollicular cells is
      described. Somatic point mutation (ATG to ACG heterozygotic mutation at codon
      918) of the RET proto-oncogene was detected in tumor tissue, as confirmed by
      immunohistochemical expression of RET oncoprotein. Our findings suggest that
      constitutive RET proto-oncogene activation may be involved in the development of
      mixed medullary-follicular thyroid carcinoma.

PMID- 11227734
TI  - Parathyroidectomy for asymptomatic primary hyperparathyroidism (PHPT): is it
      worth the risk?

PMID- 11227735
TI  - Endocrinology and art. "The Judas goiter". Unknown painter, XV century.

PMID- 11227738
TI  - Muscle reflex and central motor control of neuroendocrine activity, glucose
      homeostasis and circulation during exercise.

PMID- 11227739
TI  - Critical incident stress management and the assaulted staff action program.
AB  - Critical Incident Stress Management (CISM; Everly & Mitchell, 1999) is a clinical
      and administrative approach to address the psychological sequelae in the
      aftermath of critical incidents. CISM is a comprehensive, multicomponent crisis
      intervention procedure that spans pre-incident preparedness to acute crisis to
      post-crisis follow up. The Assaulted Staff Action Program (Flannery, 1998) is a
      voluntary, system-wide, peer-help, CISM crisis intervention program for employee
      victims of patient assault. ASAP's crisis intervention procedures and empirical
      results are used to illustrate the potential power and effectiveness of CISM
      approaches. The implications are discussed.

PMID- 11227736
TI  - Possibility of age regulation of the natriuretic peptide C-receptor in human
      platelets.
AB  - Natriuretic peptide binding sites on platelets have been hypothesized to act as
      clearance receptors; however, there is no clear definition of the function of
      this receptor. The aim of the study was: 1) to characterize natriuretic peptide
      receptors in human platelets by original competition study; 2) to evaluate a
      possible age modulation of these binding sites, since a delayed clearance of ANP
      in the elderly has been observed. The binding of 125I-ANP to intact platelets was
      completely inhibited by h-ANP, h-BNP, h-CNP and c-ANP, the selective ligand of
      the clearance receptor. IC50 values were 0.089+/-0.029, 0.703+/-0.104 and 1.19+/
      0.13, 3.84+/-0.04 nmol/l, mean+/-SE, respectively (p<0.001 for IC50 value of h
      ANP compared to the other natriuretic peptides). This observation on the receptor
      selectivity of natriuretic peptides in human platelets provides new evidence for
      the presence of the clearance receptor on platelets. In control subjects the Kd
      was 34.6+/-4.0 pmol/l and Bmax 13.6+/-0.92 fmol/10(9) platelets (mean+/-SE),
      (no.=46, mean age 41.7+/-2.1 years). Bmax was significantly reduced in older
      subjects (no.=25, mean age 53.2+/-1.5 years) with respect to the younger group
      (no.=21, mean age 28.0+/-0.87 years): 11.4+/-1.1 vs 16.1+/-1.4 fmol/10(9) cells,
      p=0.0096, respectively; moreover, a significant inverse relationship between Bmax
      and the subject's age was observed. This observation suggests a possible
      reduction of the natriuretic peptide clearance with aging, associated to a
      significant increase of plasma levels of natriuretic peptides.

PMID- 11227737
TI  - Cortistatin, but not somatostatin, binds to growth hormone secretagogue (GHS)
      receptors of human pituitary gland.
AB  - Antagonism between GH secretagogues (GHS) and somatostatin (SRIH) has been
      postulated and demonstrated, but SRIH does not bind to GHS receptors (GHS-R) and
      potent synthetic peptidyl GHS (GHRP6, hexarelin) do not displace radiolabeled
      SRIH from its receptors. However, non-natural SRIH octapeptide agonists (mainly
      lanreotide and vapreotide) displace 125I-Tyr-Ala-hexarelin from pituitary binding
      sites suggesting that an endogenous factor related to SRIH might exist and
      interact with GHS-R. Our aims were to investigate the ability of different SRIH
      like peptides such as various SRIH fragments (SRIH 3-14, SRIH 7-14, SRIH 3-10,
      SRIH 7-10, SRIH 2-9) and a natural neuropeptide that shows a high structural
      homology with SRIH such as cortistatin-14 (CST) to compete with 125I-Tyr-Ala
      hexarelin for human pituitary binding sites and to compare their binding affinity
      with that of hexarelin and ghrelin, a gastric-derived peptidyl GHS that has been
      proposed as a natural ligand of GHS-R. While the binding of 125I-Tyr-Ala
      hexarelin to pituitary membranes was completely displaced by unlabelled
      hexarelin, ghrelin and CST, none of the SRIH fragments tested inhibited this
      binding. Ghrelin and CST exhibited a similar affinity (4.6-5.4 x 10(-7) mol/l)
      for the binding while hexarelin was more effective by about four orders of
      magnitude in displacing 125I-Tyr-Ala-hexarelin. Our data demonstrate for the
      first time that cortistatin, a natural peptide related to SRIH, binds to GHS-R
      and suggest that this factor may play a role in modulating the activity of these
      receptors.

PMID- 11227740
TI  - FBI's Employee Assistance Program: an advanced law enforcement model.
AB  - As we approach the 21st century the FBI has enhanced its Employee Assistance
      Program (EAP) to include EAP services, Peer Support and Critical Incident Stress
      Management/Debriefing (CISM/D) and Chaplains' Program. This EAP is now
      anticipating the future to include a Compassion Fatigue Program for its
      counselors and coordinators, as well as developing CISD protocols for incidents
      involving weapons of mass destruction. As the FBI has accepted new challenges in
      the investigative arena throughout the world, so the FBI's Employee Assistance
      and related programs have set out to support their employees and family members
      with a continuum of integrated confidential services. The FBI recognizes that its
      most important asset is its personnel, and EAP is the vehicle to assist the FBI
      family in remaining healthy and strong for the continuous quest to fulfill its
      mission.

PMID- 11227741
TI  - Corporate response to disasters and other traumas.
AB  - Crisis intervention programs are becoming the standard of care in occupational
      environments such as law enforcement, fire suppression, emergency medicine, and
      rescue services, which are known to be at high risk for psychological morbidity.
      An area which is frequently overlooked, however, is the application of crisis
      intervention programs to businesses and other corporate environments. This paper
      describes the development and application of crisis intervention principles into
      a comprehensive psychosocial crisis management for the corporate setting
      immediately following disasters and other traumatic events. The approach used
      reinforces emergency responders' capacities of synthesis and integration as a
      systemically-oriented acute preventive intervention.

PMID- 11227742
TI  - The New South Wales Fire Brigades' critical incident stress management response
      to the Thredbo Landslide.
AB  - The Thredbo Landslide occurred just before midnight on Wednesday, July 30th,
      1997. The first call was received by the Regional Fire Communications and
      subsequently to Sydney where a multiagency response to the first Urban Search and
      Rescue (USAR) incident in Australia occurred. After ten days, eighteen bodies had
      been recovered and one survivor rescued, with one of those victims a member of
      the Thredbo Fire Brigade. Although some 2000 emergency service personnel were
      involved in the overall operation, 120 firefighters were at the forefront of the
      "hands on" rescue throughout the incident. In New South Wales the emergency
      services each have their own Critical Incident Stress Management (CISM) programs
      which operate independently from each other, and this was the case at Thredbo.
      This paper will describe how the New South Wales Fire Brigades CISM Program
      managed the Thredbo incident for the 120 New South Wales Fire Brigades
      firefighters and officers who attended the rescue operation. We are pleased to
      share this experience and what we have learned in the hope that it might be
      helpful to others.

PMID- 11227743
TI  - Psychological trauma and posttraumatic stress disorder: a review.
AB  - This paper presents a concise, fully-referenced, state-of-the-art review of
      psychological trauma and Posttraumatic Stress Disorder (PTSD) for emergency
      mental health practitioners. The nature of traumatic events, their common
      symptomatology, their disruptions to normal psychological and biological
      functioning, and the negative health consequences of untreated incidents are
      presented. Implications for the treatment of victims of traumatic events within
      the context of a Critical Incident Stress Management (CISM; Everly & Mitchell,
      1999) approach are discussed.

PMID- 11227744
TI  - A primer on critical incident stress management: what's really in a name?

PMID- 11227745
TI  - Nuclear, biological, and chemical terrorism: understanding the threat and
      designing responses.
AB  - Today nuclear, biological, and chemical (NBC) terrorism is a serious issue. The
      threat of terrorist or rogue states acquiring and using NBC weapons has ushered
      in a new age of terrorism; an age that is far more dangerous than any previous
      period. It is an age of terrorism with which no one yet knows how to deal. This
      article reviews recent trends in terrorism, and identifies groups that have both
      the potential and the motive to use weapons of mass destruction. In addition, it
      discusses the design and implemention of effective measures to meet this threat,
      as well as the role of CISM teams in preparation for, and in the aftermath of, an
      incident involving NBC weapons.

PMID- 11227746
TI  - Conditions affecting experiences of the quality of psychological debriefings:
      preliminary findings from a grounded theory study.
AB  - The aim of the study was to develop a theoretical understanding of conditions and
      mechanisms affecting experiences of the quality of emotional debriefings, using a
      grounded theory approach. Twenty interviews were conducted with experienced male
      debriefing leaders and participants in the Stockholm fire brigade and the Swedish
      armored United Nations battalions serving in Bosnia. Data were analyzed according
      to the constant comparative method. A model was formulated according to which the
      quality of debriefings is formed by the dynamic interplay between group and
      debriefing leader characteristics. The key group and debriefing leader quality is
      security. Furthermore, individual group member resourcefulness and vulnerability,
      together with the degree of knowledge and support from the management of the
      organization, also affect experiences of the quality of debriefings. The model is
      discussed in relation to existing thoughts on potentially favorable mechanisms.

PMID- 11227747
TI  - Prevalence of posttraumatic stress disorder among Kuwaiti firefighters.
AB  - It has been proven time and again that emergency service personnel experience
      much more stress than non-emergency workers. This has been a negative factor
      which affects their social, psychological, and emotional life. The purpose of the
      present study is to add to the cross-cultural data relating to the prevalence of
      posttraumatic stress among emergency services personnel, specifically
      firefighters. A random sample of 108 Kuwaiti firefighters yielded a psychometric
      prevalence of PTSD of 18.5%. These findings are consistent with data from the
      United States and from Canada.

PMID- 11227748
TI  - Welcome to the International Journal of Emergency Mental Health.

PMID- 11227749
TI  - The Assaulted Staff Action Program (ASAP) and declines in the prevalence of
      assaults: community-based replication.
AB  - The Assaulted Staff Action Program (ASAP) has been associated with sharp
      reductions in the frequency of patient assaults on staff in four state hospital
      settings. Recent national trends in healthcare have resulted in an emphasis on
      community-based services. This case study sought to assess the effects of ASAP
      and findings of reduced assaults in a community-based program. In a single-case
      design, in which the facility served as its own control, an ASAP program was
      fielded in a community mental health center. A similar sharp reduction in
      violence was observed. The implications of the findings are presented.

PMID- 11227750
TI  - The sinking of the Estonia: the effects of critical incident stress debriefing
      (CISD) on rescuers.
AB  - On the morning of September 28, 1994 the ferry Estonia sank off the coast of
      Finland. The loss of life reached 852 persons, while 137 persons were rescued.
      This study investigated the effectiveness of Critical Incident Stress Debriefing
      (CISD) as a crisis intervention process. Results of this controlled investigation
      revealed that the CISD intervention proved effective in reducing symptoms of
      distress and psychological trauma as psychometrically assessed.

PMID- 11227751
TI  - Emergency mental health: an overview.
AB  - As any field of endeavor evolves, as the field of emergency mental health is
      evolving, it becomes important to reflect upon historical milestones and define
      key terms. This paper is an effort to provide a brief overview of the field of
      emergency mental health and to take a glimpse at its future.

PMID- 11227752
TI  - The effects of critical incident stress debriefing (CISD) on emergency medical
      services personnel following the Los Angeles Civil Disturbance.
AB  - This study examined the effects of Critical Incident Stress Debriefing (CISD)
      upon technicians who provided emergency medical services in South Central Los
      Angeles during the 1992 Los Angeles Civil Disturbance. The relationships between
      exposure, debriefing and symptoms of stress were identified and examined. The
      Frederick Reaction Index-Adult (FRI-A) was used to measure the presence of
      symptoms characteristic of posttraumatic stress disorder. EMTs who had the
      opportunity to participate in Critical Incident Stress Debriefings (n = 42)
      following the incident reported fewer symptoms and scored significantly lower on
      the FRI-A than those not participating in Critical Incident Stress Debriefing (n
      = 23).

PMID- 11227753
TI  - Stress management in the Federal Bureau of Investigation: principles for program
      development.
AB  - Images from the destruction of the Alfred P. Murrah Federal Building in Oklahoma
      City, the compound in Waco, Texas, the World Trade Center in New York City, Pan
      Am Flight 103 over Lockerbie, Scotland, and the American Embassy in Nairobi,
      Kenya, burned themselves into the public's consciousness as disasters viewed from
      a distance. Many law enforcement officers and rescue workers experienced those
      images firsthand. Headlines flash in newspapers, and sound bites blare on the
      airwaves as many law enforcement professionals suffer in silence. With increasing
      frequency, such major critical incidents, as well as smaller-scale events such as
      shootings, accidents, and personal tragedies--which all emergency response
      personnel encounter throughout their careers--encroach on their daily lives and
      may cause intense stress reactions. Managers within the Federal Bureau of
      Investigation (FBI) commit to mitigating the ill effects of stressors on fellow
      employees. The FBI's Behavioral Science Unit and the Employee Assistance Unit
      work together to teach FBI employees a three-step process--how to recognize,
      understand, and cope with the stress in their lives. Given the alarming increase
      in violence, terrorism, and related crimes, there exists a myriad of
      organizations as well as other law enforcement agencies which could benefit from
      a similar formula. This paper describes how the FBI operationalizes stress
      management.

PMID- 11227754
TI  - Staying the course in stormy seas: establishing a central Critical Incident
      Stress Management team in the Navy Marine Corps environment.
AB  - Crisis response teams are becoming a standard operating procedure for most United
      States military organizations and for many military organizations outside the
      U.S. This paper describes the establishment of one specific Critical Incident
      Stress Management (CISM) team designed to provide psychological support during
      crisis, disasters, traumas, and other critical incidents that may be encountered
      in a Navy Marine Corps environment.

PMID- 11227755
TI  - Essential factors for effective psychological response to disasters and other
      crises.
AB  - Few human experiences contain the intensely concentrated horror, terror, and
      awesome power associated with a disaster. Nature's destructive forces and events
      in which humans rage out of control against one another can serve as trigger
      mechanisms for overwhelming psychological reactions in the survivors, community
      members, and rescuers. Appropriate crisis intervention strategies and tactics are
      often thrown off balance, delayed, and made more complex by the sheer magnitude
      of the catastrophe. Few guidelines for effective community crisis or disaster
      response team activities in a disaster have been written to date. This article
      will help to fill-in the information gaps and enhance a psychological team's
      ability to provide better crisis intervention services during disasters.

PMID- 11227756
TI  - Reminiscences of Hans Selye, and the birth of "stress".
AB  - The stress concept is one of the most commonly applied constructs in all of
      mental health. While the nature of stress is relatively well known, little is
      known of the man who pioneered the field. This paper provides the reader with a
      rare glimpse at the birth of the concept of stress and the man who was its
      father: Hans Selye.

PMID- 11227757
TI  - The effects of traumatic disclosure on physical and mental health: the values of
      writing and talking about upsetting events.
AB  - Directly and indirectly, sudden life transitions can profoundly influence
      people's social, family, physical, and psychological lives. One traditional goal
      within psychology has been to understand and develop ways by which to reduce the
      adverse impact of individual and collective traumas. Four major issues
      surrounding coping with emotional upheavals are discussed in the current paper.
      The first concerns the natural sequence of coping that occurs in most disasters.
      The second focuses on the advantages of talking about upsetting experiences and,
      conversely, the dangers of not talking about emotional upheavals. The third
      section, which has been central to our lab's approach, deals with evidence that
      writing about upsetting experiences is beneficial to health and well-being. The
      final part of the paper discusses these findings within the context of Critical
      Incident Stress Management (CISM) debriefing strategies.

PMID- 11227758
TI  - The transferrin receptor of Trypanosoma brucei.
AB  - Bloodstream forms of Trypanosoma brucei, the causative agent of sleeping sickness
      in humans, require transferrin for growth. Uptake of host transferrin is mediated
      by a heterodimeric glycosylphosphatidylinositol-anchored receptor. The
      trypanosomal transferrin receptor is homologous to the N-terminal domain of the
      variant surface glycoprotein (VSG) and bears no structural similarity with the
      human transferrin receptor. In this review, the structure, biochemical properties
      and function of the transferrin receptor of T. brucei are summarized and compared
      to the transferrin receptor of mammalian cells.

PMID- 11227759
TI  - Sobolevitaenia japonensis n. sp. (Dilepididae: Dilepidinae) from a dusky thrush,
      Turdus naumanni eunomus Temminck, in Oita Prefecture, Japan.
AB  - Sobolevitaenia japonensis n. sp. (Cestoda: Dilepididae) is described from eight
      specimens from the small intestine of a dusky thrush, Turdus naumanni eunomus
      Temminck, collected at Beppu City, Oita Prefecture, Japan. S. japonensis most
      closely resembles S. moldavica among the 11 species now assigned to the genus
      Sobolevitaenia, from which it is distinguished by a smaller number of
      proglottids, a larger scolex and a smaller number of testes of larger size, and a
      larger vitelline gland.

PMID- 11227760
TI  - Characterisation and expression of a cDNA encoding the 80-kDa large subunit of
      Schistosoma japonicum calpain.
AB  - We describe the cloning of a full length calpain-encoding cDNA constructed from
      two truncated cDNAs isolated from a cDNA library prepared with mRNA isolated from
      adult worms of the Philippine strain of Schistosoma japonicum. The cDNA sequence
      is 2.456 kb in length and predicts a protein of 758 residues with a molecular
      mass of 86.61 kDa and an isoelectric point of 5.34. Probes spanning the entire
      calpain cDNA hybridised to multiple bands in genomic DNAs of Philippine (SjP) and
      Chinese (SjC) S. japonicum, with some restriction fragment length polymorphisms
      evident between the two strains. Northern hybridisation analysis indicated that
      the cDNA codes for a single RNA transcript between 2.6 and 3.6 kb in size in the
      SjP and SjC genomes. After subcloning in the QIA express vectors pQE-31 and pQE
      40 and subsequent expression, the recombinant protein was purified and shown to
      bind calcium. The availability of recombinant S. japonicum calpain will allow its
      future evaluation as a vaccine candidate, especially in light of recent work with
      the S. mansoni homologue which has provided evidence that this protein may be a
      target of protective immunity.

PMID- 11227761
TI  - Evaluation of serodiagnosis of toxoplasmosis by using the recombinant nucleoside
      triphosphate hydrolase isoforms expressed in Escherichia coli.
AB  - The nucleoside triphosphate hydrolase (NTPase) isoforms termed, NTPase-I and
      NTPase-II of Toxoplasma gondii, were expressed in Escherichia coli as inclusion
      bodies and purified under denaturing condition. Furthermore, NTPase-I was
      refolded as an active form and purified under non-denaturing condition. The
      purified NTPase isoforms, both denatured and refolded, were tested for their
      usefulness as antigens for the serodiagnosis of acute toxoplasmosis in
      immunocompetent humans. The test was conducted by using the recombinant NTPase
      isoforms and comparing the enzyme linked immunosorbent assay (ELISA) absorbances
      with the Sabin-Feldman dye test titer. Seventy-three sera from dye test-positive
      patients, and 30 sera from subjects with no T. gondii infection were examined.
      The total positive rates in dye test positive sera were: 82% (60/73) for
      denatured NTPase-I; 78% (57/73) for denatured NTPase-II; and 63% (46/73) for
      refolded NTPase-I. For all three antigen types of recombinant NTPase, the
      positive rates of sera of acute toxoplasmosis suspected patients were 93%
      (13/14). A moderate correlation between the ELISA absorbance using these antigens
      and the dye test titer was observed with the correlation coefficients, 0.583 (r2)
      for denatured NTPase-I, 0.472 (r2) for denatured NTPase-II, and 0.604 (r2) for
      refolded NTPase-I in the linear regression analysis. There was no significant
      difference observed in the antigenicity between refolded and denatured NTPase-I,
      nor between the isoforms.

PMID- 11227762
TI  - Inhibition of growth of cultured Babesia microti by serum and macrophages in the
      presence or absence of T cells.
AB  - Serum and macrophages from the acute-phase (days 12-14 p.i.) and recovery-phase
      (days 23-25 p.i.) of infection of mice with Babesia microti were analyzed for
      their ability to inhibit the in vitro growth of B. microti in the presence or
      absence of T cells. Recovery-phase serum was inhibitory to the growth of B.
      microti, whereas, acute-phase serum had no inhibitory effects. Both acute- and
      recovery-phase macrophages inhibited B. microti growth. The co-culture of acute-
      but not recovery-phase T cells with macrophages from uninfected control mice was
      inhibitory to the growth of B. microti. Growth of B. microti was also inhibited
      in cultures containing macrophages from uninfected control mice plus culture
      supernatant fluid from acute-phase but not recovery-phase T cells. The
      supernatant fluid from B. microti cultures with acute-phase T cells contained IFN
      gamma detected by a sandwich ELISA, whereas cultures with control T cells or
      recovery phase T cells did not. Results of the present study suggest the
      likelihood of a protective role against B. microti in mice for antibody which
      appeared in recovery-phase serum and for macrophages activated by IFN-gamma from
      acute-phase T cells.

PMID- 11227763
TI  - Cloning and molecular characterization of calpain, a calcium-activated neutral
      proteinase, from different strains of Schistosoma japonicum.
AB  - cDNA coding for calpain of Schistosoma japonicum were cloned and sequenced, and
      serological basis of host responses to calpain were analyzed. cDNA of calpain
      from S. japonicum of two different isolates, Yamanashi strain (Sj-J) and Hunan
      strain (Sj-C), were 2, 468 bp and 2, 465 bp in length, including the same number
      (2, 274) of open reading frame. Nucleotide sequence and amino acid sequence
      between the two calpains are 99.1% and 98.8% identity, respectively. Sj-J and Sj
      C calpains were considered to be translated as a preproenzyme, and a 746-amino
      acid mature enzyme contains eight motifs without a signal peptide at the N
      terminal based on the deduced amino acid sequences. mRNA for calpain were
      detectable in different developmental stages, however, sera obtained from mice
      immunized with recombinant calpain showed enhanced binding to cercarial antigen.
      Human sera from S. japonicum-infected individuals recognized the large subunit of
      schistosomal calpain, and light-infected sera showed stronger reactivities to the
      recombinant calpain than moderate/high infection cases. When we tested synthetic
      peptides, there were four common human B cell epitopes in schistosomal calpain,
      all of which are shared with S. mansoni. Together with these results, calpain of
      S. japonicum seems to be not only a vaccine candidate, but also a target antigen
      for immunodiagnosis of human schistosomiasis.

PMID- 11227764
TI  - Sarcocystis levinei infection in Philippine water buffaloes (Bubalus bubalis).
AB  - Ultrastructural studies of sarcocysts obtained from Philippine water buffaloes
      revealed the presence of the commonly reported macroscopic species, Sarcocystis
      fusiformis, and the microscopic species Sarcocystis levinei (Dissanaike A, Kan S.
      Studies on Sarcocystis in Malaysia. I: Sarcocystis levinei n.sp. from the water
      buffalo Bubalus bubalis. Z Parasitenkd 1978;55:127-38), (Huong L, Dubey J, Uggla
      A. Redescription of Sarcocystis levinei Dissanaike and Kan, 1978 (Protozoa:
      Sarcocystidae) of the water buffalo (Bubalus bubalis). J Parasitol 1997;83:1148
      52). The globular to oval microscopic cysts commonly observed in the muscles of
      the diaphragm and neck exhibit compartmentalized arrangement of zoites with
      septal partitions and measure 13-48 microns in diameter. The parasitophorous
      vacuolar membrane of sarcocyst bears minute and hair-like villar protrusions
      measuring 2.3-2.75 microns long emanating at certain distances from the primary
      cyst wall and lack microfilaments. Villar protrusions have expanded to dome
      shaped base measuring 0.33-1.6 microns long by 0.22-1.0 micron wide, and
      intermediate and tapering distal segments bent approximately 90 degrees and run
      parallel to the cyst surface. The distal segments at some areas join to form
      conical tufts. The primary cyst wall bears numerous prominent undulations that
      are arranged in small clusters. The ground substance is 0.42-0.57 micron thick.
      This paper documents the first report of S. levinei in Philippine water buffaloes
      possessing the type 7 cyst wall.

PMID- 11227765
TI  - Geohelminthic infections associated with raw wastewater reuse for agricultural
      purposes in Beni-Mellal, Morocco.
AB  - This study was undertaken to determine the possible risk associated with raw
      wastewater use for agricultural purposes, particularly, the transmission of
      geohelminthic infections among children of five regions in Beni-Mellal, Morocco.
      In a randomly selected sample of 1343 children, 740 of them were from five
      communities using raw wastewater for agriculture, and 603 were from four control
      communities that do not practice wastewater irrigation. A questionnaire-interview
      with children and parents was used to collect data on possible demographic,
      hygiene and behavioral-contact risk factors such as sex, age, family size,
      parental education, parental occupation, source of water, toilet in house, hand
      washing, contact with wastewater and contact with wastewater irrigated land.
      Ascariasis prevalence was found to be approximately five times higher among
      children in wastewater-impacted regions compared to control regions. Contact with
      wastewater and wastewater irrigated land and public water supply were found to be
      associated with higher infection rates. Trichuris rates did not show a
      statistically significant difference between the wastewater-impacted and the
      control regions. In conclusion, raw wastewater use in Beni-Mellal can lead to a
      high risk of geohelminthic infections. Adequate treatment of wastewater and
      public health education are highly recommended.

PMID- 11227766
TI  - Human peripheral blood mononuclear cells stimulated by Schistosoma mansoni
      antigens: association between protein tyrosine kinases, mitogen-activated protein
      kinases and cytokine production.
AB  - Concerning schistosomiasis, little is known about the intracellular signaling
      response of human peripheral blood mononuclear cells (PBMC) to Schistosoma
      mansoni antigens. To understand the critical role of protein tyrosine kinases
      (PTKs) in PBMC activation by S. mansoni antigens, we investigated how inhibition
      of PTKs by genistein, a tyrosine kinase inhibitor, affects proliferation,
      cytokine production and activation of mitogen-activated protein kinases (MAPKs).
      Our studies showed that PTKs have an important role in proliferation of PBMC from
      chronic schistosomiasis patients as cells stimulated with S. mansoni soluble
      antigens in the presence of genistein had an impaired proliferation. In contrast,
      PTK inhibition failed to cause any effect on MAPKs activity. We also evaluated
      the cytokine production for interleukin (IL)-2, interferon gamma (IFN-gamma), and
      IL-10 in culture supernatants of PBMC treated with or without PTKs inhibitor. Our
      results show that PBMC from chronic patients produced a high amount of IL-10 when
      stimulated with soluble egg antigen preparation (SEA), however, the amount
      produced of IL-2 and IFN-gamma was not significant. In the presence of PTKs
      inhibitor only the production of IL-10 was decreased. The findings suggest that
      PTKs are involved on signal transduction pathway for PBMC activation, but may not
      be an absolute requirement for all signaling responses to S. mansoni antigens.

PMID- 11227767
TI  - A simple colorimetric method to screen drug cytotoxicity against Leishmania using
      the dye Alamar Blue.
AB  - A quantitative colorimetric assay using the oxidation-reduction indicator Alamar
      Blue was developed to measure cytotoxicity of compounds against the protozoan
      parasite Leishmania. Absorbance increased linearly with the plating density of
      promastigotes of L. major MRHO/IR/76 vaccine strain up to at least 2.5 x 10(6)
      cells/ml when parasites were incubated for 72 h in the presence of 10% Alamar
      Blue. The 50% effective dose values of common drugs (amphotericin B, pentostam
      and paromomycin) obtained by this assay were in the same range as previously
      determined by other methods. The Alamar Blue assay permits a simple, reproducible
      and reliable method for screening antileishmanial drugs.

PMID- 11227768
TI  - Potent in vivo antimalarial activity of 3,15-di-O-acetylbruceolide against
      Plasmodium berghei infection in mice.
AB  - The antimalarial activity of the O-acylated bruceolide derivative, 3,15-di-O
      acetylbruceolide, was evaluated against Plasmodium berghei in vivo. The
      concentration of 3,15-di-O-acetylbruceolide required for 50% suppression (ED50)
      of P. berghei in mice was 0.46 +/- 0.06 mg/kg/day, whereas bruceolide was only
      half as effective as 3,15-di-O-acetylbruceolide. Two antimalarial drugs used
      clinically, chloroquine and artemisinin, demonstrated only low activity
      corresponding to 1/4 and 1/12 of the ED50 value of 3,15-di-O-acetylbruceolide,
      respectively. These results may be helpful in the design of better
      chemotherapeutic bruceolides against falciparum malaria.

PMID- 11227769
TI  - Citation rates and impact factors: should they matter?

PMID- 11227770
TI  - Estimating periods of non-close-contact for relatives of radioactive patients.

PMID- 11227771
TI  - Case of the month. Eyes wide apart!

PMID- 11227772
TI  - MRI in the diagnosis and treatment of suspected malignant spinal cord
      compression.
AB  - It remains unclear whether MRI is essential in all patients with suspected
      malignant spinal cord compression (MSCC), or whether some patients can be treated
      on the basis of plain radiographic findings and neurological examination. A
      prospective study was carried out of 280 consecutive patients with suspected
      MSCC, and the results of neurological examination plus plain radiographs were
      compared with MRI. 201 patients had MSCC (186 extradural, 5 intradural
      extramedullary and 10 intramedullary) and 11 patients had thecal sac compression
      without evidence of spinal cord compression. 25% of patients with MSCC had two or
      more levels of compression, 69% of these involving more than one region of the
      spine. A paraspinal mass was noted at the site of extradural spinal cord
      compression in 28%, and only one-third of these were detected on plain
      radiography. Focal radiographic changes and consistent neurology were present in
      91 (33%) patients who had not had previous radiotherapy. MRI confirmed the
      presence of MSCC in 89/91 patients (specificity and positive predictive value of
      radiographic/clinical findings 98%) and the level of disease in all. MRI led to a
      change in the radiotherapy plan in 53% of patients (21% major change). The
      sensory level when present was four or more segments below the MRI level in
      25/121 (21%) patients, and two or more levels above in 8/121 (7%) patients.
      Although focal radiographic abnormalities with consistent neurological findings,
      when present, accurately predicted the presence and level of MSCC, whole spine
      MRI is indicated in most patients with suspected MSCC because the additional
      information may alter the management plan. Treatment may be appropriately
      initiated on the basis of focal radiographic changes and consistent neurology if
      MRI is contraindicated or delayed, and in patients with a poor prognosis. In
      patients in whom there are no focal radiographic abnormalities and consistent
      neurological findings, urgent MRI is mandatory before radiotherapy is commenced.

PMID- 11227773
TI  - MRI and clinical differences between optic pathway tumours in children with and
      without neurofibromatosis.
AB  - The purpose of this study was to evaluate the value of MRI in studying optic
      pathway tumours associated with neurofibromatosis, and to look for potentially
      helpful criteria for the management of such lesions. This retrospective study
      included 14 children with neurofibromatosis type 1 (NF-1) as well as a lesion of
      the optic pathway. Clinical data and MRI findings were analysed with regard to
      location, structure and course of the tumours, and were compared with 13 optic
      pathway tumours in patients without NF-1. The median age of onset was 4.1 years.
      11 patients with NF-1 were asymptomatic. In the NF-1 group, the optic nerves were
      involved in 10 cases without a cystic component at the time of diagnosis. In the
      non-NF-1 group, the tumour was located in the chiasma in 11 cases; 12 cases had a
      cystic component. 10 of the NF-1 group had no tumour progression over an average
      follow-up of 3.2 years without treatment. These findings suggest that optic
      astrocytomas in association with NF-1 are distinct lesions from isolated optic
      gliomas. In NF-1, most such tumours show only slight progression, and may
      correspond to perineural gliomatosis rather than a true pilocytic astrocytoma.
      Among NF-1 patients, initial MRI provides no prognostic criteria in children who
      subsequently show tumour progression. Nevertheless, MRI can be useful in
      establishing the diagnosis of NF-1 and can serve as a baseline study.

PMID- 11227774
TI  - Visibility of small peripheral lung cancers on chest radiographs: influence of
      densitometric parameters, CT values and tumour type.
AB  - The purpose of this study was to determine the effects of tumour density and
      tumour type on the visibility of small peripheral lung cancers on chest
      radiographs. We retrospectively evaluated the visibility of 63 small (< or = 20
      mm) peripheral lung cancers on chest radiographs. 48 (76%) were detected in our
      low dose CT screening for lung cancer and 15 (24%) in routine clinical
      examination. Analysis was based on tumour optical contrast, gradient at the
      tumour margin, CT values and tumour type. There were 31 (49%) visible cancers and
      32 (51%) invisible cancers on chest radiographs. Visible tumours had an optical
      density of 0.1-0.3 OD and a gradient of 0.03-0.11 OD mm-1. The mean size of
      visible tumour (14.3 mm) was larger than that of invisible tumour (11.1 mm; p <
      0.001). The mean CT value (-140 HU) of visible tumour was higher than that of
      invisible tumour (-490 HU; p < 0.001). The detection rates of adenocarcinomas
      with lepidic growth (0% for type A, 29% for type B and 68% for type C) were less
      than those with hilic growth (100% for types D-F). All squamous and small cell
      carcinomas with hilic growth were visible on chest radiographs, but the numbers
      of each were small. In summary, tumour type influenced the contrast, gradient, CT
      values and margin of the tumour. Small adenocarcinomas with a lepidic tumour
      growth were less well seen on chest radiographs compared with small lung cancers
      with hilic tumour growth.

PMID- 11227775
TI  - CT and bowel disease.
AB  - CT has now come of age in the detection and demonstration of bowel pathology and
      is likely to supplant traditional imaging techniques further in the future. Its
      role here has been greatly aided by the advent of fast spiral CT sequences and,
      with the development of even faster multidetector CT systems, this can only
      increase.

PMID- 11227776
TI  - Electrical impedance scanning: a new technique in the diagnosis of lymph nodes in
      which malignancy is suspected on ultrasound.
AB  - Differentiation between inflammatory and malignant lymph nodes by ultrasound is
      difficult. Electrical impedance scanning (EIS) is a new diagnostic tool, so far
      used primarily for the identification of malignant breast lesions. Cancer cells
      have altered dielectric properties compared with normal cells, thereby distorting
      the local electrical field. The induced changes in capacitance and conductivity
      are measurable using EIS. We evaluated EIS in demonstrating the cause of lymph
      node enlargement. 51 lymph nodes that were suspicious for malignancy on
      ultrasound (32 patients, mean age 32 years), with a mean size of 18 mm x 12 mm x
      10 mm, were examined. The following lymph node locations were included in the
      study: cervical, inframandibular, axillary, paraaortic and inguinal. EIS results
      were compared with histopathological and follow-up findings. 30/34 malignant
      lymph nodes were correctly detected using EIS, while 14/17 inflammatory or benign
      lymph nodes were correctly identified as benign by EIS; thus, there were 4/51
      false negative and 3/51 false positive cases. The sensitivity was 88.2% and the
      specificity was 82.4%. Corresponding negative and positive predictive values were
      77.8% and 90.9%, respectively. Results from this initial study suggest the
      potential usefulness of EIS as an adjunctive imaging modality in the
      differentiation of lymphadenopathy that is equivocal on ultrasound. The best
      accuracy was obtained in the cervical, axillary and inguinal regions. Owing to
      technical restrictions of the present system, examination of inframandibular and
      paraaortic lymph nodes should be limited to special cases.

PMID- 11227777
TI  - Skin dose and dose-area product values for interventional cardiology procedures.
AB  - Coronary angiography and percutaneous transluminal coronary angioplasty
      procedures performed in four different facilities were monitored in the present
      study by measuring maximum skin dose, dose-area product and other operational
      parameters. Radiographic slow film, thermoluminescent dosemeters and transmission
      ion chambers were used to measure dose related quantities. Values of 107-711 mGy
      for maximum skin dose and 27.3-370.6 Gy cm2 for dose-area product were found,
      together with cumulative skin dose estimates of 110-3706 mGy. A discussion of the
      relationship of measured dose-area product and skin dose values is made using a
      field concentration factor defined as a way to interpret the findings. No general
      correlation was observed between dose-area product and maximum skin dose.
      Cumulative skin dose estimates throughout a procedure should be discarded as a
      realistic method for assessing deterministic risk in cardiology procedures. Slow
      film in addition to thermoluminescent dosemeters for measurement of maximum skin
      dose is a good alternative, especially for complex interventional procedures. For
      repeated procedures, combining film and dose-area product monitoring favours
      optimization of radiation protection for the patient.

PMID- 11227778
TI  - A purpose-built iodine-125 irradiation plaque for low dose rate low energy
      irradiation of cell lines in vitro.
AB  - The phenomenon of hyper-radiosensitivity (HRS) to very low acute single doses of
      radiation has been demonstrated in several cell lines in vitro and in vivo, and
      has been studied in theory and in practice. The theory suggests a similar
      hypersensitivity when cells are continuously exposed to radiation at very low
      dose rates. These low dose rates are used when radioactive seed (iodine-125 or
      palladium-103) implants of the prostate are used as an alternative to surgery or
      external beam radiotherapy. To investigate the radiobiology of hypersensitivity
      of this type on various cell lines in vitro, an iodine-125 seed irradiator has
      been designed and built for safe use in the Gray Laboratory. In practice, the
      calculated dose rate has been used for consistency. Discrepancies between
      calculated and measured dose rates are discussed.

PMID- 11227779
TI  - A generic approach to risk assessment for the Ionising Radiations Regulations
      1999.
AB  - The Ionising Radiations Regulations 1999 (IRR99) require that an explicit risk
      assessment be carried out to control properly the risks associated with the use
      of ionising radiation. Prior to IRR99, risk was controlled implicitly via
      mechanisms such as Local Rules and staff monitoring, which were initiated by the
      Radiation Protection Adviser using professional judgement. To enable a consistent
      approach across our Trust's radiation users, a generic model of risk assessment
      was employed. This had been developed previously by the Trust in response to a
      national initiative within the NHS to manage risk. The methodology involves the
      generation, by a multidisciplinary staff brain-storming session, of a complete
      list of all possible risks. This is followed by a risk stratification process
      based upon severity of consequence and frequency of risk. Auditable controls are
      then applied and quantifiable outcome measures are monitored for continued
      compliance. Template risk assessments are presented to aid others in this
      process. It is estimated that even in a large teaching hospital with a full
      complement of medical radiation applications, the time resource necessary for
      this approach is of the order of a few days.

PMID- 11227780
TI  - A digital frame of reference for viewing digital images.
AB  - Digital imaging is becoming widespread in diagnostic radiology. Most diagnostic
      digital images do not relate explicitly to the physical processes involved in
      their generation but are, in essence, a "pseudo" image generated from digital
      data using pre- and post-processing. Without knowledge of how the image was
      generated, there is a potential to misinterpret the image data. A new design of
      digitally generated graphic is presented that is intended to help maintain the
      frame of reference when viewing digitally processed images. The intention is that
      the digital frame of reference (DFOR) be included with all digitally processed
      images and be processed using the same factors as were used on the image. An
      unprocessed DFOR can then be displayed adjacent to the processed DFOR to re
      introduce a frame of reference and to clearly illustrate the effect of any
      processes that have been applied to the image. This would allow the viewer to
      perceive any artefacts that may have been introduced into the image by the
      processing. This is particularly important where the image requires
      interpretation by the viewer, as in medical diagnosis. This paper presents a grey
      scale version of the DFOR that is suitable for applications such as medical
      imaging. The DFOR includes: grey scale from 0 to the maximum bit depth in 0%,
      30%, 70% and 100% steps on a 50% background; the full frequency range from 0 to
      the Nyquist frequency; high, medium and low contrast boundaries; and
      linear/curvilinear features. The same method could be extended to any other
      digital image system and could be easily modified to include colour.

PMID- 11227781
TI  - Variation in size and position of the planning target volume in the transverse
      plane owing to respiratory movement during radiotherapy to the lung.
AB  - Movement of thoracic tumours with respiration poses a real dilemma in terms of
      the accuracy of delivering radical radiotherapy in patients with carcinoma of the
      lung. Movements in the craniocaudal direction have previously been described.
      This technical note describes ten patients planned for radical lung radiotherapy
      using CT. The study assesses the maximum impact of respiration on the planning
      target volume in the transverse plane by comparing the planning CT appearances
      during quiet respiration with those during full inspiration and full expiration.
      The study demonstrated the potential impact of respiratory movement on the
      planning target volume and, hence, implications for local tumour control.

PMID- 11227782
TI  - In vivo radioprotection of mouse brain endothelial cells by Hoechst 33342.
AB  - Radiation-induced loss of mouse brain endothelial cells has been examined in mice
      given an intravenous injection of the DNA-binding radioprotector Hoechst 33342
      (80 mg kg-1). At the time of irradiation, 10 min after injection, Hoechst
      fluorescence in the brain was confined to the endothelial cells. Endothelial cell
      density was measured using a histochemical fluorescence technique that had been
      used previously to monitor post-irradiation changes in endothelial cell density
      in rat brain, in which it was shown that a sensitive subpopulation comprising
      about 15% of the endothelial cells was lost within 24 h of radiation exposure.
      The present study shows a similar dose-response for the control mice, with
      depletion of the sensitive subpopulation to 85% being almost complete after a
      dose of 2.5 Gy gamma-rays. However, in mice irradiated 10 min after Hoechst 33342
      administration, doses between 12 Gy and 20 Gy were required to ablate these
      cells. The kinetics of cell loss and the rather large dose modification factor
      suggests that Hoechst 33342 may be suppressing an apoptotic response in this
      subpopulation. Whatever the mechanism involved, Hoechst 33342 clearly provides
      substantial protection against early radiation-induced endothelial cell loss.
      Further studies are necessary to determine the extent to which this initial
      protection translates into an improved long-term survival of the "protected"
      cells and, especially, to see whether this endothelial cell protection can
      ameliorate the later consequences of central nervous system irradiation, namely
      necrosis and paralysis.

PMID- 11227783
TI  - Cerebral cryptococcosis: atypical appearances on CT.
AB  - Cryptococcal infection is common in immunocompromised patients, often presenting
      with meningitis or meningoencephalitis. We report an unusual presentation of
      cryptococcal infection in an immunocompetent patient presenting with headache and
      hemiplegia. CT demonstrated a large ring-enhancing lesion in the parietal region
      with intralesional calcification.

PMID- 11227784
TI  - Pulmonary hypertension secondary to left-sided heart disease: a cause for
      ventilation-perfusion mismatch mimicking pulmonary embolism.
AB  - Ventilation-perfusion (V/Q) scans are commonly performed in patients with
      suspected pulmonary thromboembolism (PE). V/Q mismatch is typically attributed to
      PE. We describe a case in which a V/Q scan performed on a patient with advanced
      hypertrophic obstructive cardiomyopathy showed large areas of V/Q mismatch not
      due to PE. The mismatch was due to pulmonary hypertension secondary to left-sided
      heart disease. The pathophysiology is briefly reviewed.

PMID- 11227785
TI  - Lobar atelectasis: diagnostic pitfalls on chest radiography.
AB  - This pictorial review looks at the pitfalls in the diagnosis of lobar atelectasis
      on chest radiographs. Lobar atelectasis with marked volume loss is hard to
      recognize and may be easily missed. Lobar atelectasis presenting as a mass-like
      opacity may be misdiagnosed as mediastinal or lung tumour. Lobar atelectasis in
      an unusual location may also be misdiagnosed as other entities. Familiarity with
      such manifestations and consideration of anatomical alterations as the signs of
      lobar atelectasis are important in making the correct diagnosis.

PMID- 11227786
TI  - X-ray leakage considerations for IMRT.

PMID- 11227787
TI  - R403Q and L908V mutant beta-cardiac myosin from patients with familial
      hypertrophic cardiomyopathy exhibit enhanced mechanical performance at the single
      molecule level.
AB  - Familial hypertrophic cardiomyopathy (FHC) is a disease of the sarcomere. In the
      beta-myosin heavy chain gene, which codes for the mechanical enzyme myosin,
      greater than 40 point mutations have been found that are causal for this disease.
      We have studied the effect of two mutations, the R403Q and L908V, on myosin
      molecular mechanics. In the in vitro motility assay, the mutant myosins produced
      a 30% greater velocity of actin filament movement (v(actin)). At the single
      molecule level, v(actin) approximately d/t(on), where d is the myosin unitary
      step displacement and t(on) is the step duration. Laser trap studies were
      performed at 10 microM MgATP to estimate d and t(on) for the normal and mutant
      myosin molecules. The increase in v(actin) can be explained by a significant
      decrease in the average t(on)'s in both the R403Q and L908V mutants
      (approximately 30 ms) compared to controls (approximately 40 ms), while d was not
      different for all myosins tested (approximately 7 nm). Thus the mutations affect
      the kinetics of the cross-bridge cycle without any effect on myosin's inherent
      motion and force generating capacity. Based on these studies, the primary signal
      for the hypertrophic response appears to be an apparent gain in function of the
      individual mutant myosin molecules.

PMID- 11227788
TI  - Frog skeletal muscle fibers recovering from fatigue have reduced charge movement.
AB  - Following prolonged exercise, muscle force production is often impaired. One
      possible cause of this force deficit is impaired intracellular activation. We
      have used single skeletal muscle fibers from the lumbrical muscle of Xenopus
      laevis to study the effects of fatigue on excitation-contraction coupling.
      Fatigue was induced in 13 intact fibers. Five fibers recovered in normal Ringer
      only (fatigued-only fibers). The remaining eight fibers were subjected to a brief
      hypotonic treatment (F-H fibers) that is known to prolong the effects of fatigue.
      Intramembrane charge movement, changes in intracellular calcium concentration
      ([Ca2+]i) and force transients were measured in a single Vaseline gap chamber
      under voltage clamp. In F-H fibers, membrane capacitance was reduced. Confocal
      microscopy showed that this was not due to closure of the transverse tubules. The
      amount of normalized intramembrane charge was reduced from 21.0 +/- 2.8 nC/microF
      (n = 10) in rested fibers to 12.2 +/- 1.1 nC/microF in F-H fibers. However, the
      voltage dependence of intramembrane charge movement was unchanged. In F-H fibers,
      force production was virtually abolished. This was the consequence of the greatly
      reduced [Ca2+]i accompanying a depolarizing pulse. In recovering fatigued-only
      fibers, while the maximal available charge was not significantly smaller (18.3 +/
      1.1 nC/ microF), both calcium and force were reduced, albeit to a lesser extent
      than in F-H fibers. The data are consistent with a model where fatigue reduces
      the number of voltage sensors in the t-tubules and, in addition, alters the
      coupling between the remaining functional voltage sensors and the calcium
      channels of the sarcoplasmic reticulum.

PMID- 11227789
TI  - Crossbridge kinetics in single frog muscle fibres in presence of ethylene glycol.
AB  - Single fibres isolated from frog muscle were tetanically stimulated at 14 degrees
      C to produce isometric tetani at a sarcomere length of about 2.16 microm, using a
      striation follower device to measure the sarcomere length of a selected segment
      of fibre. Force-velocity data were obtained by applying ramp releases at pre-set
      velocity at the tetanus plateau. Sarcomere stiffness was measured at isometric
      plateau and during isotonic shortening by using sinusoidal length changes at 2
      kHz frequency and about 1 nm per half sarcomere (hs) peak to peak amplitude. A
      correction method was used to compensate for the force truncation due to the
      quick recovery. After data collection, the bathing solution was substituted with
      Ringer plus ethylene glycol (EG) at 2 M (11.2% v/v). When the fibre was fully
      equilibrated with the new solution, the measurements were repeated. Ethylene
      glycol reduced the speed of the tetanus rise and tetanus relaxation without
      altering the isometric tension, and reduced the maximum shortening velocity by
      about 20%. During isotonic contraction tension and stiffness at each given
      shortening velocity were reduced by about the same amount, so that the
      stiffness/tension ratio remained almost unaltered. Force-velocity and stiffness
      data in both standard and EG Ringer were analysed in terms of a two state model
      (Huxley, 1957). The analysis showed that our results can be accounted for by
      assuming that EG at 2 M concentration reduces all the rate constants for
      crossbridges interaction by about the same amount.

PMID- 11227790
TI  - Urocortin hyperpolarizes stomach smooth muscle via activation of Ca2+-sensitive
      K+ currents.
AB  - The effect of urocortin (Uro), a recently discovered neuropeptide with
      selectivity towards corticotropin-releasing hormone type 2 receptor, was tested
      on whole cell currents expressed by guinea-pig gastric antrum smooth muscle
      cells. Uro (1 pmol/l-1 nmol/l) caused a concentration-dependent increase of Ca2+
      sensitive K currents (I(K)) up to 500% as compared to control currents and did
      not affect the kinetics and voltage-dependence of inward Ca2+ currents. The I(K)
      increasing effect of Uro was fully antagonized by preliminary emptying of
      intracellular Ca2+ stores with ryanodine and cyclopiazonic acid, as well as by
      bath application of selective blockers of adenylyl cyclase and cAMP-dependent
      protein kinase (PKA), but not by inhibitors of guanylyl cyclase, cGMP-dependent
      protein kinase, and protein kinase C. Comparable I(K) increase was obtained by
      forskolin (activator of adenylyl cyclase), Sp-cAMPS (activator of PKA), or by
      intracellular application of the catalytic subunit of PKA. It was concluded that
      Uro binds to a selective receptor in antral smooth muscle cells where it
      stimulates I(K) via PKA-dependent increase of Ca2+ concentration near the plasma
      membrane due to enhanced release from intracellular calcium stores.

PMID- 11227791
TI  - The expression of the myogenic regulatory factors in denervated and normal
      muscles of different phenotypes.
AB  - The nerve is known to play a pivotal role in the diversification of muscle fibre
      types postnatally. Reducing neuronal activity in a slow muscle such as the soleus
      by denervation, switches on genes associated with a fast muscle phenotype. On the
      other hand, denervating a fast muscle such as the extensor digitorum longus (EDL)
      induces the conversion of fast fibres to a 'slower' contractile phenotype. The
      myogenic regulatory factors (MRFs) are proposed as the regulators of muscle
      phenotype as MyoD and myogenin have been shown to differentially accumulate in
      fast and slow muscle upon the induction of fibre type transformation. The
      denervation model has been used in the present study to induce changes in MRF
      expression in the muscles of the lower hindlimb which have distinct phenotypic
      characteristics. The level of MRF expression in pairs of denervated and
      innervated soleus, EDL, tibialis anterior (TA), plantaris and gastrocnemius
      muscles has been determined by Northern analysis and compared. The present study
      has shown that each muscle responds differently to denervation with respect to
      the increases in MRF expression. Fast muscles responded very quickly to
      denervation by increasing the level of MRF transcripts while slow muscles did not
      show significant increases in expression after 48 h denervation. The innervated
      EDL (fast) and soleus (slow) muscle differed with respect to the level of MRF-4
      expressed, MRF-4 being expressed at higher levels in the slow muscle compared to
      the fast, suggesting that MRF-4 is important in the maintenance of a slow muscle
      phenotype. Moreover, MRF-4 and myogenin show the greatest fold increases in
      expression in the fast muscles examined. MyoD and Myf 5 show less dramatic
      increase in expression in response to denervation but exhibit the greatest fold
      increases in the fast muscles compared to slow.

PMID- 11227792
TI  - Glycogen stability and glycogen phosphorylase activities in isolated skeletal
      muscles from rat and toad.
AB  - There is increasing evidence that endogenous glycogen depletion may affect
      excitation-contraction (E-C) coupling events in vertebrate skeletal muscle. One
      approach employed in physiological investigations of E-C coupling involves the
      use of mechanically skinned, single fibre preparations obtained from tissues
      stored under paraffin oil, at room temperature (RT: 20-24 degrees C) and 4
      degrees C for several hours. In the present study, we examined the effect of
      these storage conditions on the glycogen content in three muscles frequently used
      in research on E-C coupling: rat extensor digitorum longus (EDL) and soleus (SOL)
      and toad iliofibularis (IF). Glycogen content was determined fluorometrically in
      homogenates prepared from whole muscles, stored under paraffin oil for up to 6 h
      at RT or 4 degrees C. Control muscles and muscles stored for 0.5 and 6 h were
      also analysed for total phosphorylase (Phos(total)) and phosphorylase a (Phos a)
      activities. No significant change was observed in the glycogen content of EDL and
      SOL muscles stored at RT for 0.5 h. In rat muscles stored at RT for longer than
      0.5 h, the glycogen content decreased to 67.6% (EDL) and 78.7% (SOL) of controls
      after 3 h and 25.3% (EDL) and 37.4% (SOL) after 6 h. Rat muscles stored at 4
      degrees C retained 79.0% (EDL) and 92.5% (SOL) of glycogen after 3 h and 75.2%
      (EDL) and 61.1% (SOL) after 6 h. The glycogen content of IF muscles stored at RT
      or 4 degrees C for 6 h was not significantly different from controls. Phos(total)
      was unchanged in all muscles over the 6 h period, at both temperatures. Phos a
      was also unchanged in the toad IF muscles, but in rat muscles it decreased
      rapidly, particularly in EDL (4.1-fold after 0.5 h at RT). Taken together these
      results indicate that storage under paraffin oil for up to 6 h at RT or 4 degrees
      C is accompanied by minimal glycogen loss in toad IF muscles and by a time- and
      temperature-dependent glycogen loss in EDL and SOL muscles of the rat.

PMID- 11227793
TI  - Ca2+- and Sr2+-activation properties of muscle fibres from a muscle receptor
      organ and the associated extrafusal muscle of the crab and crayfish.
AB  - In this study on decapod crustaceans, we examined the Ca2+- and Sr2+-activation
      properties of skeletal muscle fibres from an identified proprioceptor, the
      thoracic coxal muscle receptor organ (TCMRO) and its extrafusal promotor muscle
      fibres. Proprioceptors and extrafusal muscles were isolated from a walking leg
      from the crayfish (Cherax destructor) and the rear swimming leg of the mud crab
      (Scylla serrata). The crayfish and mud crab TCMROs had very low Hill coefficient
      (nCa) values (1.86 +/- 0.08 and 1.64 +/- 0.03, respectively). In comparison to
      other skeletal muscle fibre types these low Hill coefficients would enable the
      length of the receptor muscles to be finely controlled over a wide range of
      [Ca2+]. Maximum force was found to be significantly lower in the TCMROs
      (crayfish: 5.76 +/- 0.98; crab: 4.80 +/- 0.56 Ncm(-2)), compared to their
      associated extrafusal promotor muscle fibres (crayfish: 10.69 +/- 1.63; crab:
      20.07 +/- 1.98 Ncm(-2)), which is consistent with their sensory role. The muscle
      fibres of the crayfish TCMRO had faster contractile properties than the mud crab
      TCMRO, we discuss how these contractile properties relate to the type of
      locomotion undergone by each leg. The mud crab 'red' promotor and all crayfish
      promotor fibres were characterised as slow with low Hill coefficients (nCa:
      crayfish: 3.22 +/- 0.29; crab: 3.34 +/- 0.29) and a contractile apparatus with a
      high sensitivity to Ca2+ (pCa50: crayfish: 6.42 +/- 0.03; crab: 6.18 +/- 0.03).
      In contrast the 'white' mud crab promotor fibres from the swimming leg had
      contractile properties that were characteristic of fast fibres with a high mean
      Hill coefficient (nCa: 5.27 +/- 0.76) and a lower Ca2+ sensitivity (pCa50: 6.03
      +/- 0.03). The sensitivity of the contractile apparatus to Sr2+ was very low
      (range of mean pSr50: 4.23 +/- 0.03-3.48 +/- 0.06) and low force levels were
      produced in comparison to that produced with Ca2+. The results of this study show
      that the muscle fibres of the sensory receptor, produce less force and have been
      adapted to enable the length of the receptor to be finely set in relation to the
      length of the extrafusal muscle. We discuss how the striated fibres of the
      receptor have been adapted to perform a sensory role and how this is related to
      the type of locomotion undergone by the legs. We also discuss how the fibre types
      of the extrafusal muscle have adapted to the mode of locomotion.

PMID- 11227794
TI  - Jaw-closing muscles of kangaroos express alpha-cardiac myosin heavy chain.
AB  - The masseter muscle of eutherian grazing mammals typically express beta or slow
      myosin heavy chain (MyHC). Myosins in the masseter of 4 species of kangaroos and
      a slow limb muscle of one of them were compared with their cardiac myosin by
      pyrophosphate and sodium dodecyl sulphate (SDS) gel electrophoresis,
      immunoblotting and immunohistochemistry. It was found that ventricular muscle
      contains three isoforms homologous to V1 (alpha-MyHC homodimer), V2 (heterodimer)
      and V3 (beta-MyHC homodimer) of eutherian cardiac muscle, and that the masseter
      contained V1, with traces of V2 and V3, in great contrast to eutherian ruminants,
      which express only V3. A polyclonal antibody (anti-KJM) was raised in rabbits
      against red kangaroo masseter myosin. After cross-absorption against limb muscle
      myofibrils, anti-KJM specifically reacted in Westerns with MyHCs from masseter
      but not limb muscles, and immunohistochemically with masseter, but not limb
      muscle fibers. In pyrophosphate Western blots, anti-KJM reacted with V1 but not
      with V3. However, a monoclonal antibody specific for eutherian slow myosin
      stained all kangaroo slow muscle fibers but only weakly stained scattered fibers
      in the masseter. The SDS-PAGE revealed that light chain composition of masseter
      and ventricular myosins is identical, but isoforms of both light chains of
      kangaroo limb slow myosin were observed. These results confirm that kangaroo jaw
      muscle express alpha-MyHC rather than beta-MyHC. The difference in MyHC gene
      expression between marsupial and eutherian grazers may be related to the fact
      that kangaroos are not ruminants, and have only a single chance to comminute food
      into fine particles, hence the need for the greater speed and power of muscle
      contraction associated with V1 containing muscle fibers.

PMID- 11227795
TI  - A-band architecture in vertebrate skeletal muscle: polarity of the myosin head
      array.
AB  - Despite extensive knowledge of many muscle A-band proteins (myosin molecules,
      titin, C-protein (MyBP-C)), details of the organization of these molecules to
      form myosin filaments remain unclear. Recently the myosin head (crossbridge)
      configuration in a relaxed vertebrate muscle was determined from low-angle X-ray
      diffraction (Hudson et al. (1997), J Mol Biol 273: 440-455). This showed that,
      even without C-protein, the myosin head array displays a characteristic polar
      pattern with every third 143 A-spaced crossbridge level particularly prominent.
      However, X-ray diffraction cannot determine the polarity of the crossbridge array
      relative to the neighbouring actin filaments; information crucial to a proper
      understanding of the contractile event. Here, electron micrographs of negatively
      stained goldfish A-segments and of fast-frozen, freeze-fractured plaice A-bands
      have been used to determine the resting myosin head polarity relative to the M
      band. In agreement with the X-ray data, the prominent 429 A-spaced striations are
      seen outside the C-zone, where no non-myosin proteins apart from titin are
      thought to be located. The head orientation is with the concave side of the
      curved myosin heads (containing the entrance to the ATP-binding site) facing
      towards the M-band and the convex surface (containing the actin-binding region at
      one end) facing away from the M-band.

PMID- 11227796
TI  - Coupling of creatine kinase to glycolytic enzymes at the sarcomeric I-band of
      skeletal muscle: a biochemical study in situ.
AB  - The specific interaction of muscle type creatine-kinase (MM-CK) with the
      myofibrillar M-line was demonstrated by exchanging endogenous MM-CK with an
      excess of fluorescently labeled MM-CK in situ, using chemically skinned skeletal
      muscle fibers and confocal microscopy. No binding of labeled MM-CK was noticed at
      the I-band of skinned fibers, where the enzyme is additionally located in vivo,
      as shown earlier by immunofluorescence staining of cryosections of intact muscle.
      However, when rhodamine-labeled MM-CK was diffused into skinned fibers that had
      been preincubated with phosphofructokinase (PFK), a glycolytic enzyme known to
      bind to actin, a striking in vivo-like interaction of Rh-MM-CK with the I-band
      was found, presumably mediated by binding of Rh-MM-CK to the glycolytic enzyme.
      Aldolase, another actin-binding glycolytic enzyme was also able to bind Rh-MM-CK
      to the I-band, but formation of the complex occurred preferably at long sarcomere
      length (> 3.0 microm). Neither pyruvate kinase, although known for its binding to
      actin, nor phosphoglycerate kinase (PGK), not directly interacting with the I
      band itself, did mediate I-band targeting of MM-CK. Anchoring of MM-CK to the I
      band via PFK, but not so via aldolase, was strongly pH-dependent and occurred
      below pH 7.0. Labeling performed at different sarcomere length indicated that the
      PFK/MM-CK complex bound to thin filaments of the I-band, but not within the
      actomyosin overlap zones. The physiological consequences of the structural
      interaction of MM-CK with PFK at the I-band is discussed with respect to
      functional coupling of MM-CK to glycolysis, metabolic regulation and channeling
      in multi-enzyme complexes. The in situ binding assay with skinned skeletal muscle
      fibers described here represents a useful method for further studies of specific
      protein-protein interactions in a structurally intact contractile system under
      various precisely controlled conditions.

PMID- 11227797
TI  - Genetic analysis of the requirements for alpha-actinin function.
AB  - Null alpha-actinin mutations in Drosophila are lethal and produce conspicuous
      defects in muscle structure and function. Here, we used transgene rescue to
      examine the requirements for alpha-actinin function in vivo. First, we tested the
      ability of a cDNA-based transgene encoding the adult muscle isoform of alpha
      actinin under control of the heterologous ubiquitin promoter to rescue the
      lethality of null alpha-actinin mutations. Successful rescue indicated that
      alternative splicing, which also generates larval muscle and non-muscle isoforms,
      was not essential for viability and that there were no strict spatial or temporal
      requirements for alpha-actinin expression. Secondly, chimeric transgenes, with
      functional domains of alpha-actinin replaced by similar domains from spectrin,
      were tested for their ability to rescue alpha-actinin mutants. Replacement of
      either the actin binding domain or the EF hand calcium binding domain yielded
      inactive proteins, indicating that these conserved domains were not functionally
      equivalent. Thirdly, the length of alpha-actinin was modified by adding a 114
      amino acid structural repeat from alpha-spectrin to the center of the rod domain
      of alpha-actinin. Addition of this sequence module was expected to increase the
      length of the native alpha-actinin molecule by at least 15%. yet was fully
      compatible with alpha-actinin function as measured by rescued lethality and
      flight. Thus, unexpectedly, the exact length of alpha-actinin was not critical to
      its function in the muscle Z disk.

PMID- 11227798
TI  - Soybean allergens and hypoallergenic soybean products.
AB  - About 15 soybean proteins were shown to be recognized by sera of soybean
      sensitive patients with atopic dermatitis. Three of them were identified as major
      allergens and designated as Gly m Bd 60K, Gly m Bd 30K, and Gly m Bd 28K,
      respectively. Gly m Bd 60K is an alpha subunit of beta-conglycinin well known as
      a major soybean storage protein. Gly m Bd 30K is also known as a soybean oil-body
      associated glycoprotein with a molecular weight of 34,000, which is homologous to
      Der p (or f) 1, a major allergen of house dust mite, classified under the papain
      super family. Gly m Bd 28K is a vicilin-like glycoprotein with a molecular weight
      of 26,000, a minor component fractionated into 7S globulin fraction. The
      reduction of allergenicity of soybean and soybean products has been developed
      with respect to the above-mentioned major three allergens as the targets by the
      use of the combined techniques of a chemical breeding, a physico-chemical
      treatment, and an enzymatic digestion. Among the three major allergens, the alpha
      subunit of beta-conglycinin and Gly m Bd 28K were eliminated from soybean seeds
      by the development of a mutant line, Tohoku 124, introduced by a chemical
      breeding technique. The strongest allergen, Gly m Bd 30K, was almost completely
      removed from defatted soymilk prepared from Tohoku 124 by a salting-out technique
      and a centrifugation under the limited pH and ionic strength and alternatively by
      an enzymatic digestion. By the application of these procedures, several
      hypoallergenic soybean products, such as cooked soybean grains, soybean curd
      (Tofu), and fermented soybean paste (Miso), soymilk, and a jelly-like soybean
      cake have been made to evaluate their usefulness by a challenge test for soybean
      sensitive patients. It has been demonstrated by a preliminary trial that about
      80% of the soybean-sensitive patients could ingest these hypoallegenic products
      without any adverse reactions.

PMID- 11227799
TI  - Effects of graded levels of dietary casein and corn oil on total cholesterol and
      triacylglycerol in plasma and liver of rats.
AB  - With the intention of examining the effects of dietary protein and oil levels on
      total cholesterol (T-CHOL) and triacylglycerol (TG) concentrations in the plasma
      and liver, male Wistar rats, weighing about 170 g, were fed diets containing
      graded levels of casein and corn oil for 2 wk. At the 5, 20, and 30% levels of
      dietary corn oil, plasma T-CHOL concentrations were generally enhanced in
      proportion to the rise of dietary casein level, but plasma TG contents were
      scarcely influenced by the level. At the 8 to 35% casein levels, plasma T-CHOL
      and TG concentrations were the highest at the 5% corn oil level, followed in
      order by the 20 and 30% levels of oil. At the 5 and 20% oil levels, hepatic T
      CHOL contents were hardly changed at the 8 to 30% casein levels, but enhanced at
      the 35% casein level. At the 30% oil level, the T-CHOL contents tended to be
      changed proportionally to casein levels. At all levels of casein, hepatic T-CHOL
      contents tended to be relatively high at the 30% corn oil, middle at the 20% oil,
      and low at the 5% one. At each corn oil level, TG contents in the liver tended to
      be elevated at the 8 to 15% casein levels and highly preserved at the 15 to 25%
      ones. Then, the raised TG contents declined at the 5 and 20% levels of corn oil
      and remained constant at the 30% oil. At each casein level, the contents of
      hepatic TG were generally high at the 30% oil level, followed in order by the 20
      and 5% oil levels. These results indicated that plasma and liver T-CHOL
      concentrations were proportionately enhnaced by the increase in casein level, and
      plasma TG contents were hardly affected by the level and hepatic TG ones were
      lowered by relatively lower or higher casein level, and the rise in corn oil
      level generally reduced plasma T-CHOL and TG concentrations, but raised hepatic
      ones.

PMID- 11227800
TI  - Serum biomarker-based validation of a self-administered diet history
      questionnaire for Japanese subjects.
AB  - Although several self-administered dietary assessment questionnaires have been
      developed for Japanese subjects, they have seldom been validated with objective
      measures. We validated a recently developed self-administered diet history
      questionnaire (DHQ) with fatty acids in serum phospholipid fractions, alpha- and
      beta-carotenes and alpha-tocopherol in serum as a gold standard using 86
      university workers (42 men and 44 women, age-range=24-67 y). The age-adjusted
      Pearson partial correlation coefficients between the intakes of marine origin n-3
      polyunsaturated fatty acids (PUFA) (crude values, energy-adjusted values by
      residual method, energy density, and fat density) and the serum phospholipid
      concentrations (percentage of total fatty acids) were 0.49, 0.51, 0.52, 0.48, and
      0.58, 0.69. 0.66, 0.69 in men and women respectively. The correlation
      coefficients between intakes (microg/d) and the corresponding serum
      concentrations (micromol/L) were 0.43 and 0.40 in men and 0.42 and 0.60 in women
      for alpha- and beta-carotene respectively. It was -0.23 in men and -0.22 in women
      for alpha-tocopherol. The intakes of major foods (g/d) of marine origin n-3 PUFA,
      alpha- and beta-carotenes showed a relatively high level of correlation with the
      corresponding serum concentrations, whereas the level was generally lower than
      those observed in the analysis with the nutrient intakes. The results suggest
      that DHQ ranks individual adequately for marine origin n-3 PUFA, alpha- and beta
      carotene intakes.

PMID- 11227801
TI  - Hyperlipemia and early pancreatic injury induced by ethanol intake in rats.
AB  - The pathogenesis of alcoholic pancreatitis is unknown, and even though
      hyperlipemia has been hypothesized to be a risk factor for alcoholic
      pancreatitis, no studies directly investigating whether there is a relationship
      between the two have ever been reported. Therefore, to determine if a
      relationship exists between hyperlipemia and alcoholic pancreatitis, especially
      the early stage of alcoholic pancreatic injury, we administered a regular liquid
      Lieber-DeCarli diet, with and without ethanol as 35% of total calories, to rats
      for 2 wk. Thereafter we measured their plasma lipid concentrations, pancreatic
      zymogen granule fragility, and plasma lipase activity and subsequently
      investigated the correlations between these parameters. Significant increases in
      plasma triglyceride, total cholesterol, phospholipid, nonesterified fatty acid,
      pancreatic zymogen granule fragility, and plasma lipase activity were observed in
      the ethanol liquid diet group, compared with the values of the control liquid
      diet group, and pancreatic zymogen granule fragility was correlated with plasma
      triglyceride (r=0.62), total cholesterol (r=0.77), phospholipid (r=0.76),
      nonesterified fatty acid concentrations (r=0.62), and lipase activity (r=0.63).
      These results show a possible relationship between hyperlipemia and the early
      stage of alcoholic pancreatic injury, and they may support the hypothesis that
      hyperlipemia contributes to the etiology of alcoholic pancreatitis.

PMID- 11227802
TI  - Oleyl alcohol inhibits intestinal long-chain fatty acid absorption in rats.
AB  - Long-chain fatty acids are important nutrients, but obesity is the most common
      nutritional disorder in humans. In this study we investigated the effect of oleyl
      alcohol on the intestinal long-chain fatty acid absorption in rats. We
      administered [14C]oleic acid and oleyl alcohol as lipid emulsion intraduodenally
      in unanesthetized lymph-cannulated rats and measured the lymphatic output of
      oleic acid. Second, we orally administered lipid emulsion with a stomach tube and
      measured the luminal and mucosal oleic acid residues. Furthermore, rats were fed
      oleyl alcohol as a dietary component for 20 days, and fecal lipid and the weight
      of adipose tissues were measured. In lymph-cannulated rats, triglyceride and
      [14C]oleic acid output in the lymph were significantly lower in the presence of
      oleyl alcohol when compared with the absence of oleyl alcohol in a dose-dependent
      manner. The radioactivity remaining in the intestinal lumen was more strongly
      detected in rats that had been orally administered oleyl alcohol than in the
      controls. The feces of rats fed an oleyl-alcohol-added diet contained much higher
      amounts of lipids, and the weights of their adipose tissues were significantly
      lower than in the control group. These results suggest that oleyl alcohol
      inhibits the rat gastrointestinal absorption of long-chain fatty acids in vivo.

PMID- 11227803
TI  - Effects of capsaicin-containing yellow curry sauce on sympathetic nervous system
      activity and diet-induced thermogenesis in lean and obese young women.
AB  - The present study was designed to investigate the effect of capsaicin, a pungent
      component of red pepper, on the sympathetic nervous system (SNS) activity and
      energy metabolism in 16 age- and height-matched lean and obese young women. The
      sympatho-vagal activities were assessed by means of spectral analysis of heart
      rate variability (HRV) during the resting condition and after the meal (2,016 kJ)
      with capsaicin (3 mg). Energy expenditure was also measured under the two
      conditions. There was no significant difference in any of the parameters of the
      HRV between the obese and control groups at rest. After the capsaicin diet,
      however, the very low frequency component (0.007-0.035 Hz) associated with
      thermogenesis (315.8+/-78.0 vs. 814.8+/-211.7 ms2 x Hz(-1), p<0.05) as well as
      its responsiveness (delta changes: 14.6+/-104.4 vs. 369.2+/-121.7 ms2 x Hz(-1),
      p<0.05) were significantly lower in the obese than the control group. Energy
      expenditure was significantly increased in the control group after the meal
      (5,574.7+/-221.2 to 6,114.7+/-239.0 kJ day(-1); p<0.01), but no such significant
      thermogenic response was detected in the obese group despite nearly identical
      lean body mass of the control group. Our data indicate that regardless of the
      resting level of sympatho-vagal activities, the reduced sympathetic
      responsiveness to physiological perturbation such as a capsaicin diet, which may
      cause impaired diet-induced thermogenesis and further weight gain, could be an
      important etiological factor leading to obesity in young women.

PMID- 11227805
TI  - A simple and rapid method for the routine assay of total ascorbic acid in serum
      and plasma using ascorbate oxidase and o-phenylenediamine.
AB  - A simple and rapid analysis of total ascorbic acid (AsA) in serum and plasma and
      its automated analysis are described. AsA is oxidized by ascorbate oxidase (AsA
      oxidase) to dehydroascorbic acid that then reacts with o-phenylenediamine (OPDA)
      to form a quinoxaline derivative that absorbs at 340 nm. The change in absorbance
      is directly proportional to the total AsA concentration. The assay was validated
      with a linear concentration range of 0.8-80 mg/L, and the within-day and between
      day assays precision did not exceed 8.6% and 12.5%, respectively. On 47 sera, the
      manual enzymatic procedure gave 0.2 mg/L on average lower values than those of an
      automated enzymatic procedure with a correlation coefficient of 0.847. On another
      66 sera, results by automated enzymatic method correlated well with the HPLC
      method and the regression equation is Y (enzymatic, automated)=0.97 X (HPLC)+0.1,
      r=0.980, Sy.x=0.6 mg/L. An experienced analyst can perform about 24 manual assays
      per hour whereas the automated procedure gave a rate of 100 assays per hour.

PMID- 11227804
TI  - Coffee and fitness-coffee suppresses lipopolysaccharide-induced liver injury in
      rats.
AB  - To clarify the relationship between coffee and fitness, we investigated the
      effect of coffee on weight gain and total cholesterol as well as production of
      cytokines and activities of GOT (aspartate aminotransferase; EC 2.6.1.1.) and GPT
      (alanine aminotransferase; EC 2.6.1.2.) as injected lipopolysaccharides. Forty
      eight male Wistar rats were divided into three dietary groups (n=16), which were
      fed a stock diet (control group), the diet supplemented with freeze-dried coffee
      of 6.2 g/kg (0.62% coffee group), and the diet supplemented with freeze-dried
      coffee of 13.6 g/kg (1.36% coffee group). It was confirmed by HPLC analysis that
      the serum caffeine concentrations in both coffee groups became significantly
      higher in 140 days after the start of feeding. No significant differences in body
      weight and serum cholesterol were found between the coffee groups and control
      group, though the coffee groups tended to be somewhat high at cholesterol level.
      Activities of serum GOT and GPT increased at 2 h after LPS injection, but in the
      coffee groups were significantly suppressed (p<0.05). However, the coffee feeding
      could not suppress the increases of serum cytokine (TNF-alpha and IL-6) levels.
      These results suggest that coffee may serve as a preventive against liver injury.

PMID- 11227806
TI  - Effects of pH variation and NaCl on in vitro digestibility of cow's milk proteins
      in commercially available infant formulas.
AB  - Allergenicity and antigenicity of food proteins are generally dependent on their
      heat-stability and resistance to digestive enzymes. Using the methods of SDS-PAGE
      and immunoblots, we assessed peptic-digestibility of major milk proteins (casein,
      beta-lactoglobulin and alpha-lactalbumin) in commercially available infant
      formulas in acidic pH range (pH 1.5 to 4.0), and we also investigated the effect
      of NaCl on peptic-digestibility of cow's milk proteins at pH 2.0. The profile of
      peptic-digestion of casein was similar at pH range from 1.5 to 3.5 where the
      intact protein of casein rapidly disappeared, whereas slow digestibility of the
      protein was found at pH 4.0. Beta-lactoglobulin and alpha-lactalbumin were
      digested at pH range from 1.5 to 2.5 and were almost entirely resistant to peptic
      digestion at over pH 3.0. In the presence of NaCl at pH 2.0, casein showed a good
      digestibility by pepsin similar to that in the absence of NaCl, in contrast to
      beta-lactoglobulin and alpha-lactalbumin both having their peptic-digestibility
      decreased in the presence of 0.2 M NaCl. As the state of the stomach in new born
      infants shows low amounts of secretary pepsin and out of optimum pH of peptic
      activity, low digestibility of beta-lactoglobulin and alpha-lactalbumin in cow's
      milk based infant formulas at over pH 3.0 is supposed to be responsible for their
      allergenicity.

PMID- 11227807
TI  - The causal link between self-reported trauma and dissociation: a critical review.
AB  - The idea that traumatic experiences cause dissociative symptoms is a recurrent
      theme in clinical literature. The present article summarizes evidence that cast
      doubts on the commonly voiced view that the connection between self-reported
      trauma and dissociation is a simple and robust one. It is argued that: (1) the
      correlations between self-reported traumatic experiences and dissociative
      symptoms reported in the literature are, at best, modest; (2) other factors may
      act as a third variable in the relationship between trauma and dissociation; and
      (3) high scores on the Dissociative Experiences Scale are accompanied by fantasy
      proneness, heightened suggestibility, and susceptibility to pseudomemories. These
      correlates of dissociation may promote a positive response bias to retrospective
      self-report instruments of traumatic experiences. Thus, the possibility that
      dissociation encourages self-reported traumatic experiences rather than vice
      versa merits investigation. While attractive, simple models in which trauma
      directly causes dissociation are unlikely to be true.

PMID- 11227808
TI  - Is pessimism a risk factor for depressive mood among community-dwelling older
      adults?
AB  - This study examined two senses in which pessimism might be a risk factor for
      depressive mood among older adults. The first was that a pessimistic explanatory
      style would predict changes toward depressive mood when combined with stressful
      life events. The second was that predictive pessimism, or thinking that bad
      events will happen in the future, would predict changes in depressive symptoms.
      We found an interaction between explanatory style and life stressors, but it was
      the optimists who were at higher risk for depressive symptoms after negative life
      events. We also found support for predictive pessimism, however, as a predictor
      of depressive symptoms over time.

PMID- 11227809
TI  - Familial correlates of social anxiety in children and adolescents.
AB  - Retrospective studies suggest a relationship between parental rearing practices
      and social phobia. The present study investigated whether socially anxious
      children perceive their current parental rearing as rejecting, overprotective,
      and lacking emotional warmth, and as emphasizing the importance of other's
      opinion, and de-emphasizing social initiatives and family sociability.
      Furthermore, we examined whether parents of socially anxious children report to
      rely on such rearing practices, and suffer themselves from social fears. A
      regression analysis as well as extreme group comparisons were applied. Little
      support was found for the presumed role of the assessed family rearing aspects in
      the development of social anxiety in children. Solely family sociability
      (children's and mothers' report) and children's perception of overprotection of
      the mother predicted social anxiety in the regression analysis. Given the
      influence of the mentioned rearing practices, social anxiety of the mother still
      significantly predicted social anxiety of the child. In the extreme group
      comparisons, differences in the expected direction were found between socially
      anxious and normal children on parental rejection, emotional warmth, and family
      sociability. However, the lack of differences between socially anxious and
      clinical control children suggests that these variables do not form a specific
      pathway to social fears.

PMID- 11227810
TI  - Social phobia and avoidant personality disorder as related to parental history of
      social anxiety: a general population study.
AB  - Using a validated and DSM-IV compatible questionnaire, the present study related
      family history of excessive social anxiety to social phobia and avoidant
      personality disorder (APD) in epidemiologically identified probands in the
      general population. Probands met diagnostic criteria for social phobia with or
      without APD and APD with or without social phobia. A two- to three-fold increased
      relative risk of social anxiety was observed for all diagnostic groups.
      Increasing severity in probands by varying diagnostic criteria did not affect the
      relative risk. Because familial aggregation of social anxiety was not modulated
      by Axis I or II diagnosis or diagnostic cut-off levels, data imply that social
      phobia and APD may represent a dimension of social anxiety rather than separate
      disorders. Thus, having an affected family member is associated with a two- to
      three-fold risk increase for both social phobia and APD.

PMID- 11227811
TI  - Evaluation of manual-based cognitive-behavioral therapy for bulimia nervosa in a
      service setting.
AB  - In the present study manual-based cognitive-behavioral therapy for bulimia
      nervosa was evaluated on an unselected sample of an out-patient service facility.
      A total of 73 female patients who asked for treatment received the primary
      diagnosis of bulimia nervosa. Of these, 67 took up treatment. Treatment was
      completed by 66 patients. Outcome variables were the number of binge episodes
      along with questionnaire scores for restraint eating, emotional eating, body
      dissatisfaction and depressiveness. At the end of treatment and 1 year after the
      end of treatment significant improvements were found in all outcome variables.
      Effect sizes for outcome variables were within the range of those of controlled
      research. Therefore, the present study delivered empirical evidence that manual
      based cognitive-behavioral therapy is an effective treatment for bulimia nervosa
      not only within the restricted area of research.

PMID- 11227812
TI  - On Wakefield's harmful dysfunction analysis of mental disorder.
AB  - Wakefield's harmful dysfunction analysis of mental disorder is among the most
      rigorous and thoughtful attempts to address serious conceptual problems that
      beset the foundations of abnormal psychology. According to Wakefield, disorder is
      a hybrid concept comprising a factual component specifying derangement in a
      naturally-selected function, and a value component specifying the resultant harm.
      It is unclear, however, whether an evolutionary interpretation of dysfunction is
      either feasible or necessary; a nonhistorical causal role analysis of
      psychological function may enable ascription of disorder (assuming resultant
      harm). Moreover, the dysfunction component itself appears hybrid, comprising both
      a factual assertion about the state of a mechanism and a normative assertion
      implying that the mechanism is not functioning as it ought be.

PMID- 11227813
TI  - The diagnostic and statistical manual's new white coat and circularity of
      plausible dysfunctions: response to Wakefield, part 1.
AB  - Wakefield has claimed: (1) logical empiricist models of scientific progress
      support the view that expansions of the modern DSMs are consistent with such
      standards of progress; (2) diagnostic label proliferation of the modern DSMs is
      the same phenomenon as change in physical disease labels of the ICDs; (3) the
      concepts of disorder and dysfunction should not be separated. I show: (1)
      Wakefield has misrepresented traditional philosophy of science models of progress
      to serve his rhetorical aims: (2) Wakefield's claim that DSM label proliferation
      and ICD change are the same is empirically false; (3) failure to separate the
      concept of disorder from the concept of dysfunction leads to erroneous reasoning
      and label proliferation observed in the modem DSMs.

PMID- 11227814
TI  - Evolutionary history versus current causal role in the definition of disorder:
      reply to McNally.
AB  - The harmful dysfunction (HD) analysis (Wakefield, American Psychologist 47
      (1992a) 373) asserts that "disorder" means "harmful dysfunction", where "harm" is
      a value concept anchored in social values and "dysfunction" is a factual concept
      referring to failure of a mechanism to perform a natural function. Additionally,
      the HD analysis claims that a mechanism's natural functions are its naturally
      selected effects. McNally (Behaviour Research and Therapy (2000) pp. 309-314)
      argues to the contrary that "dysfunction" is a value concept referring to
      negative failures of function, that "function" refers to current causal roles and
      not evolutionarily designed causal roles, and that "disorder" consequently means
      "harmful failure of a mechanism to perform a valued current causal role." I reply
      by showing that McNally's proposals lack the HD analysis's power to explain
      common judgments about function, dysfunction, and disorder. "Dysfunction" cannot
      be a negative value concept because many dysfunctions are positive or neutral;
      "function" cannot refer to current causal roles because many current causal roles
      are not functions and some functions are not current causal roles; and "disorder"
      cannot refer to harmful failures of current causal roles because that definition
      allows almost any negative condition whatever to be a disorder and thus fails to
      explain the distinctions we make between disorder and non-disorder.

PMID- 11227815
TI  - Estimating the 5-percentile of the species sensitivity distributions without any
      assumptions about the distribution.
AB  - A non-parametric method is described to estimate the hazardous concentration for
      p% of the species, the HCp, and the confidence limits for this value, the
      HCp(alpha). For this method, all observed sensitivities are ordered from high to
      low sensitivity. The HC5 is the k-th observation were k is the largest integer
      below 0.05 x (n + 1). It is described how the HCp(alpha) can be calculated. A
      table is presented for easy calculation of several conservative confidence limits
      for the HC5. For the HC5(0.05), a second table is presented which can be used to
      interpolate between the conservative estimate of the HC5(0.05) and the next
      higher observed concentration. The non-parametric HC5 and HC5(0.05) estimation is
      illustrated with an example of sensitivity data on malathion. For this data set,
      the log-normal HC5 and HC5(0.05) estimations appear to be conservative compared
      with the non-parametric estimate. It is stressed that HC5 and HC5(0.05) estimates
      will often be much more affected by the non-randomness of the species set for
      which sensitivity data are available than by the choice of the statistical
      method.

PMID- 11227816
TI  - Polycyclic aromatic hydrocarbon-polluted dredged peat sediments and earthworms: a
      mutual interference.
AB  - In lowland areas of the Netherlands, any peat sediments will gradually become
      enriched with anthropogenically derived Polycyclic Aromatic Hydrocarbons. Due to
      Dutch policy standards these (anaerobic) sediments are not allowed to be dredged
      and placed onto land. Under aerobic conditions, however, biodegradation of PAH is
      greatly enhanced. This degradation is further stimulated by colonisation of the
      sediments by earthworms. Laboratory experiments show that although earthworms do
      not avoid PAH-contaminated sediment, their burrowing-activity is reduced.
      Furthermore, these sediments have no significant ecotoxicological impacts on
      earthworms. Experimental introduction of earthworms into PAH-contaminated OECD
      soil will result in a decrease in overall PAH content. In field surveys no
      significant differences in earthworm numbers between locations with fresh and old
      sediment could be found. It is concluded that dredging of PAH-contaminated
      sediment poses a very limited environmental threat, and that putting these
      sediments on land will improve PAH-biodegradation, partly through the
      colonisation by and activities of earthworms.

PMID- 11227818
TI  - Variability of physicochemical and biological parameters between replicated
      outdoor freshwater lentic mesocosms.
AB  - Micro- and mesocosms are frequently required in regulatory procedures of aquatic
      risk assessment for pesticides. However, many questions are still a matter of
      debate with regard to the use of these systems for environmental risk assessment,
      especially considering the inter-system variability of the measured parameters
      and its consequences on experimental design and data analysis. In this paper,
      variability of physico-chemical and biological parameters measured during two
      long-term experiments (8 to 9 months) in uncontaminated outdoor freshwater lentic
      mesocosms (8 m3) is analysed. Consequences on the design of ecotoxicity tests in
      mesocosms and on data analysis are also addressed. Water temperature, pH,
      dissolved oxygen concentration and concentration of suspended solids exhibited a
      very low variability whereas nutrient concentrations displayed elevated levels of
      variability. Among biological parameters, those measured at the individual level
      were less variable than those measured at the community level. Functional
      descriptors frequently exhibited a lower inter-mesocosm variability than
      structural descriptors. Aggregation of data proved to significantly reduce inter
      mesocosm variability. The results indicate that univariate statistical methods
      may be used for physico-chemical or species-level (e.g. biometric parameters)
      data which exhibit a moderate inter-mesocosm variability. The use of multivariate
      techniques is suggested for other levels of investigation. Nevertheless,
      variability is not sufficient to identify useful parameters. The sensitivity
      towards chemicals and ecological relevance of descriptors within the experimental
      context must also be considered.

PMID- 11227817
TI  - Immunotoxicity in invertebrates: measurement and ecotoxicological relevance.
AB  - Concern is growing regarding the impact of chemicals suspected of altering the
      function of the immune system in humans and wildlife. There are numerous examples
      of links between pollution and increased susceptibility to disease in wildlife
      species, including immunosuppression in harbour seals feeding on fish from
      contaminated sites, altered immune function in riverine fish and decreased host
      resistance in birds exposed to pollutants. Laboratory tests have identified
      potential immunological hazards posed by a range of anthropogenic chemicals in
      mammals and higher vertebrates. However, few reports have considered the
      ecological relevance of pollution-induced immunosuppression in invertebrate
      phyla, which constitute around 95% of all animal species and occupy key
      structural and functional roles in ecosystems. In this paper effects of chemicals
      on immune function in invertebrates are briefly reviewed and biomarkers of
      immunotoxicity are identified. Examples of new approaches for the measurement of
      immunological inflammatory reactions and stress in molluscan haemocytes are
      detailed. The relevance of defining the immune system as a target organ of
      toxicity in invertebrates is discussed and an integrated approach for the use of
      immunological biomarkers in environment management is proposed, combining
      measures of immune function and organismal viability at the biochemical, cellular
      and population level.

PMID- 11227819
TI  - Utility of zanamivir for chemoprophylaxis of concomitant influenza A and B in a
      complex continuing-care population.

PMID- 11227820
TI  - Pseudomonas dermatitis/folliculitis associated with pools and hot tubs--Colorado
      and Maine, 1999-2000.

PMID- 11227821
TI  - Death from invasive meningococcal disease following close contact with a case of
      primary meningococcal conjunctivitis--Langley, British Columbia, 1999.

PMID- 11227822
TI  - Progress toward interrupting indigenous measles transmission--region of the
      Americas, January 1999-September 2000.

PMID- 11227823
TI  - An Advisory Committee Statement (ACS). National Advisory Committee on
      Immunization (NACI). Supplementary statement on influenza vaccination: continued
      use of Fluviral influenza vaccine in the 2000-2001 season.

PMID- 11227824
TI  - An Advisory Committee Statement (ACS). Committee to Advise on Tropical Medicine
      and Travel (CATMAT). Statement on hepatitis A vaccines for travellers.

PMID- 11227825
TI  - Seasonal population dynamics of ixodes ticks and tick-borne encephalitis virus.
AB  - Seasonality of the epidemic and epizootic processes of tick-borne encephalitis
      (TBE) depend on the period of activity of ixodid ticks Ixodes persulcatus Schulze
      and I. ricinus Linnaeus, which are the main reservoirs and vectors of TBE virus,
      and also on the process of their activation. The period of activity is the period
      during which the ticks occur in the active state. Activation is the transition
      into this state of ticks that moulted from the preceding stage and completed post
      moulting development. For I. persulcatus, the first adult ticks generally emerge
      between April 10 and May 9. Under a variety of natural conditions, activation of
      adult I. persulcatus after wintering lasts for 45-86 days and this period may be
      even longer in certain areas of the Far East. The period during which one-half of
      the entire tick population becomes activated (AT50) comprises no more than 10-20
      days. In adult I. ricinus ticks the activation period may last even longer than
      in I. persulcatus. The data on duration of the period of activity and on
      activation of larval and nymphal stages of both tick species were considered.
      Ticks exhausting their nutrient reserves and failing to find a host die quickly.
      The period during which 50% of the entire tick population die under natural
      conditions is designated LT50. The main types of I. persulcatus and I. ricinus
      seasonal activity within their species ranges were reviewed. Data on the
      relationship between TBE virus reproduction in a natural focus and physiological
      age, pattern of activation, and seasonal changes in age structure of the tick
      population were analyzed. Seasonal changes in the prevalence of infection among
      active unfed adult ticks in a natural population are determined by virus content
      in individual ticks at the moment of their activation and also by the duration of
      subsequent virus persistence (the rate of virus loss) in ticks. Apparently, the
      opportunity and frequency of horizontal TBE virus transmission under natural
      conditions, change during the season of tick activity.

PMID- 11227826
TI  - Life cycle of the tick Haemaphysalis leporis-palustris (Acari: Ixodidae) under
      laboratory conditions.
AB  - The life cycles of two separate populations (colonies A and B) of the rabbit
      tick, Haemaphysalis leporis-palustris, were studied under laboratory conditions.
      Domestic New Zealand rabbits, Oryctolagus cuniculus, and wild rabbits, Sylvilagus
      brasiliensis, were used as hosts for ticks from colony B and only O. cuniculus
      rabbits were used as hosts for ticks from colony A. Developmental periods were
      observed in an incubator at 27+/-1 degrees C and RH 90+/-5%. Larvae from colonies
      A and B fed for 8.0+/-3.7 days and 8.5+/-1.3 days, respectively, on O. cuniculus.
      On S. brasiliensis larvae from colony B fed for 7.2+/-1.3 days. Nymphs from
      colony A fed for 8.1+/-1.4 days on O. cuniculus and nymphs from colony B fed for
      8.1+/-1.0 days on S. brasiliensis. Only one engorged nymph from colony B was
      recovered from O. cuniculus. Females from colony A fed for 20.9+/-5.9 days on O.
      cuniculus and females from colony B fed for 18.6+/-2.4 days on O. cuniculus and
      18.7+/-3.7 days on S. brasiliensis. Engorged larvae from colony A required 13.7+/
      3.7 days to molt while engorged larvae from colony B required 11.8+/-3.0 and
      11.5+/-1.8 days to molt, after having fed on O. cuniculus and S. brasiliensis,
      respectively. Engorged nymphs from colonies A and B required 16.3+/-1.9 days and
      14.7+/-1.4 days to molt, respectively. Engorged females from colonies A and B
      required 4-7 and 3-5 days, respectively, to start oviposition. Mean egg
      incubation periods lasted for 33-34 days. For ticks from colony B, host species
      accounted for significant differences (p < 0.05) in larval and nymphal feeding
      periods, oviposition weights and CEIs. Significant differences (p < 0.05) between
      the two colonies when ticks fed on O. cuniculus were observed for larval and
      nymphal feeding and premolt periods, engorged female and oviposition weights and
      conversion efficiency indexes (CEI). S. brasiliensis were always a more suitable
      host for H. leporis-palustris than O. cuniculus. Significantly more larvae and
      nymphs engorged and molted when fed on S. brasiliensis (p < 0.001). Females fed
      S. brasiliensis were more successful to lay fertile eggs and showed the highest
      engorged and egg mass weights, and the highest CEIs. Data of H. leporis-palustris
      fed on wild rabbits (one of its natural host species) are reported for the first
      time.

PMID- 11227827
TI  - Host seeking activity of ixodes ricinus ticks based on daily consecutive flagging
      samples.
AB  - The seasonality of I. ricinus was studied by three daily consecutive flaggings in
      four sites situated in an ecotone between a spruce forest and a peaty meadow, a
      spruce forest, a beech forest and a dense spruce forest. First day flagging
      samples represent the most commonly used method for description of tick
      seasonality. Since two consecutive flaggings remove ticks in the vegetation,
      third day flagging samples represent the number of ticks ascending into the
      vegetation, which was interpreted as being closely related to the size of the
      free living tick population. First day samples of nymphs were reasonably
      consistent with the typical bimodal seasonal pattern of activity (Gray, 1991).
      Third day samples showed a more stable seasonal development with no or only
      limited bimodality. The host seeking period or retention time in the vegetation,
      as defined by the ratio between first and third day samples differed within the
      season. The host seeking periods were found to be long in the spring, short in
      midsummer and intermediate in autumn. By analysing the host seeking period for
      dependency of weather parameters, it was found that host seeking periods
      primarily depend on relative humidity and solar radiation. No significant
      difference in tick abundance in third day samples could be related to weather
      conditions.

PMID- 11227828
TI  - Cannibalism and intraguild predation among phytoseiid mites: are aggressiveness
      and prey preference related to diet specialization?
AB  - We tested whether specialist and generalist phytoseiid mites differ in
      aggressiveness and prey choice in cannibalism and intraguild predation.
      Specialists tested were Galendromus occidentalis, Neoseiulus longispinosus,
      Phytoseiulus persimilis, and P. macropilis; generalists tested were Amblyseius
      andersoni, Euseius finlandicus, E. hibisci, Kampimodromus aberrans, Neoseiulus
      barkeri, N. californicus, N. cucumeris, NM fallacis, and Typhlodromus pyri.
      Aggressiveness of cannibalistic females against larvae was not related to diet
      specialization except that highly aggressive species were exclusively
      generalists. Seldom to moderately cannibalizing species occurred in both
      generalist and specialist phytoseiids. In contrast to aggressiveness in
      cannibalism, generalists and specialists differed in aggressiveness in intraguild
      predation. Adult females of specialists were only slightly aggressive against
      heterospecific larvae, whereas adult females of all generalists except T. pyri
      were highly aggressive. Adult females of generalists were able to discriminate
      between con- and heterospecific larvae and preferentially consumed the latter
      when given a choice. Adult females of specialists except G. occidentalis showed
      no preference when given a choice between con- and heterospecific larvae. We
      conclude that aggressiveness in intraguild predation, species recognition and
      subsequent preferential consumption of heterospecifics when given a choice is
      common in generalist but not specialist phytoseiids. We discuss the evolutionary
      pathways that might have led to the difference between specialists and
      generalists in species discrimination.

PMID- 11227829
TI  - Contamination of passenger trains with Dermatophagoides (Acari: Pyroglyphidae)
      mite antigen in Japan.
AB  - Passenger trains were surveyed for contamination with Dermatophagoides farinae
      Hughes and Dermatophagoides pteronyssinus (Trouesart) mites in Japan. A total of
      492 dust samples were collected from upholstered seats in six commuter trains,
      one long-distance express train and three night trains in October, 1996 and
      January, April, and July, 1997. Mite antigen levels contained in fine dust
      fractions of these samples were measured by an enzyme-linked immunosorbent assay.
      Most samples obtained from commuter trains showed relatively high mite antigen
      levels of > 10 microgm(-2) (corresponding to > 100 mites). Express and night
      trains showed lower antigen levels per square meter, but higher mite antigen
      levels per gram of fine dust than commuter trains, indicating relatively high
      mite antigen densities. Seasonal comparisons indicated that commuter trains
      showed the highest mean antigen level per square meter in winter (January),
      whereas the highest antigen level per gram of fine dust was observed in summer
      (July) in express and night trains.

PMID- 11227830
TI  - Differences in biological characteristics in organophosphorus-resistant strains
      of the phytoseiid mite Typhlodromus pyri.
AB  - Strains of Typhlodromus pyri were collected from orchards in SW England, where
      populations differed in their response to organophosphorus insecticides compared
      with strains collected in the SE. Biological characteristics of these strains
      were compared with those in OP-resistant strains collected from the SE and OP-
      susceptible strains. There were significant differences in size of eggs and adult
      mites from the different strains, but these differences did not appear to be
      related to resistance status of the mites. Female OP-susceptible mites had a
      longer development time than other strains. Over all strains total development
      time for female mites was 0.8 day less than for males. There were significant
      differences between strains for pre-oviposition period, but not oviposition or
      post-oviposition periods. There were significant differences in total numbers of
      eggs produced between strains, with a standard OP-resistant strain producing the
      most and an OP-susceptible strain the fewest eggs. There were significant
      differences in male longevity between strains, but this did not appear to be
      related to resistance status. This study highlights the fact that strains may
      differ in biological characteristics that contribute to fitness regardless of
      their pesticide resistance status.

PMID- 11227831
TI  - "Beyond cost-containment in health care".

PMID- 11227832
TI  - Familial hypercholesterolaemia in a Belgian community.
AB  - Familial hypercholesterolaemia (FH) is a genetic disease in which low-density
      lipoproteins are defectively removed from plasma as a result of mutations that
      impair the function either of the LDL receptor or of the apolipoprotein B. The
      consequences are an elevated concentration of LDL-cholesterol and the early
      occurrence of cardiovascular diseases. Although FH is well understood, it remains
      a diagnostic challenge for the clinician. Differentiating FH from other causes of
      hypercholesterolaemia has, however, important clinical and therapeutic
      implications: FH being associated with early and severe cardiovascular risk, the
      plasma LDL-cholesterol must be lowered as drastically and as early as possible;
      because FH is a dominantly inherited disorder, family members need to be screened
      and counseled. Prevalence, morbidity and genetic characterization of FH have
      never been explored in our country. Through our experience of large-scale
      screening of LDL-receptor and Apo B amongst suspected individuals, we are
      beginning to understand the molecular spectrum of FH in Belgium. Furthermore,
      using the large collection of clinical data accumulated amongst patients with
      genetically ascertained FH, we have attempted to establish specific and sensible
      diagnostic criteria useful and feasible in routine medical practice.

PMID- 11227833
TI  - Contribution of the peak exercise QT dispersion to the accuracy of an exercise
      test during the evaluation of coronary artery disease.
AB  - OBJECTIVE: Regional defects in ventricle repolarization are extremely sensitive
      to ischaemia which can be measured as QT dispersion (QTd). We investigated the
      role of QTd calculated at the time of peak exercise during treadmill studies.
      METHODS AND RESULTS: Thirty-three women and eighty men, whose treadmill test
      results and coronary angiography studies had been examined, were divided into
      four groups according to the test results: 1) subjects with a negative treadmill
      test and without significant stenosis results in the angiography, were considered
      normal (N; n = 35); 2) subjects with both a positive exercise test and a
      significant presence of stenotic coronary arteries, were considered true positive
      (TP; n = 52); 3) subjects with a positive exercise test, but without significant
      stenosis results in the angiography, were considered false positive (FP; n = 14);
      4) subjects with a negative treadmill study, despite significantly stenotic
      arteries, were considered false negative (FN; n = 12). All subjects were
      evaluated on the basis of age, significant ST-segment depression, peak heart
      rate, rest and peak exercise QT, and QpT (measured from the beginning of the QRS
      complex to the highest point of the T wave) dispersion, and corrected (QTcd,
      QpTcd) values for heart rate. The most significant differences were observed
      between the N and the TP groups in terms of QTd and QTcd (p < 0.01), with a
      higher correlation (r = 0.48). A significant relationship was also observed in
      terms of QpT and QpTcd values during peak exercise (p < 0.01). The sensitivity of
      the peak exercise QTcd and QTcd > or = 70 ms in determining coronary artery
      disease was found to be 74%. In cases of QTcd > or = 70 ms, in addition to ST
      segment depression, the test was found to be less sensitive, but more specific at
      96%. CONCLUSION: It suggests that when peak exercise QTd and QpTd values are
      taken into account, with the exception of the ST-segment depression, the accuracy
      of the exercise test will increase and false positive results will decrease.

PMID- 11227834
TI  - Recent findings on return to work after an acute myocardial infarction or
      coronary artery bypass grafting.
AB  - OBJECTIVE: To examine during recent years the rate of work resumption after an
      acute myocardial infarction or coronary artery bypass surgery, and to analyse
      variables that predicted return to work. SETTING: Referral centre for cardiac
      rehabilitation at the university hospital in Gent. PATIENTS: 227 consecutive
      patients (90 after a first AMI; 137 after a first CABG) were selected for
      participation. All patients were less than 60 years old and in a social state
      that still allowed return to work. During hospitalisation, a set of
      questionnaires, validated as well as self-developed, was presented, measuring
      psychological and social variables. Medical variables were collected from the
      medical records. One year later, a follow-up questionnaire was sent by mail,
      measuring return to work, reasons for not returning, morbidity, and psychological
      well-being. RESULTS: Return to work was observed in 185/222 (83.3%) of the total
      study group; 75/86 (87.2%) of the AMI patients and 110/136 (80.8%) of the CABG
      patients. The mean delay for return to work was 14.8 weeks. After one year,
      patients who returned to work, showed more positive affect, less negative affect,
      less somatic complaints and less cognitive complaints. This better psychological
      profile was not affected by the morbidity score. Variables predicting return to
      work in CABG patients were different from those in AMI patients. Only two medical
      variables could be retained in CABG patients (good left venticular function and a
      larger degree of revascularisation). Mainly psychological variables had
      predictive power (trust, job security, positive expectations concerning return,
      no attribution to stress, less somatic complaints, less physical exertion of the
      job). CONCLUSIONS: Return to work remains one of the main issues in cardiac
      rehabilitation after AMI or CABG. If resumption is sufficiently emphasized, a
      high success rate can be achieved. This approach should include a psychosocial
      strategy starting already during hospitalisation.

PMID- 11227835
TI  - Tilt testing in neurocardiogenic syncope: isosorbide versus isoproterenol.
AB  - OBJECTIVE: To compare the diagnostic value of pharmacological stimulation with
      sublingual isosorbide dinitrate and intravenous isoproterenol during tilt testing
      in patients with neurocardiogenic syncope and with a negative tilt test without
      pharmacological provocation. METHODS AND RESULTS: One hundred and twenty patients
      with a history of neurocardiogenic syncope (aged 15 to 77 years) and 50 healthy
      volunteers (aged 25 to 70 years) were prospectively submitted to head-up tilt
      (HUT). Those who did not develop syncope or presyncope during passive HUT for 30
      minutes underwent repeated HUT with isoproterenol infusion at 4 microg/min (ISOP
      HUT), for 10 minutes, and, subsequently, were tilted after sublingual
      administration of 5 mg of isosorbide dinitrate (ISDN HUT) for another 12 minutes.
      ISDN HUT was always performed after ISOP HUT. Sensitivity and specificity of
      passive HUT were 41% (95% C.I. 32.9% to 51.0%) and 100%, respectively.
      Sensitivity of ISOP HUT was 51.4% (95% C.I. 39.2% to 63.6%) and specificity 70%
      (95% C.I. 55.4% to 82.1%) and for ISDN HUT were 70% (95% C.I. 57.9% to 80.4%) and
      88% (95% C.I. 75.7% to 95.5%), respectively. The accuracy of ISDN HUT was
      significantly higher than the accuracy of ISOP HUT 77.5% (95% C.I. 68.9% to
      84.6%). There were fewer side effects during ISDN HUT. CONCLUSION: Sublingual
      isosorbide dinitrate is at least as sensitive as isoproterenol to assess patients
      with suspected neurocardiogenic syncope and with a negative tilt test without
      provocation. The low rate of side effects and the higher accuracy of ISDN HUT,
      along with the simplicity of this challenge compared to ISOP HUT, suggest that
      sublingual isosorbide dinitrate should be preferred as a provocative agent to
      evaluate neurocardiogenic syncope after a negative passive tilt test.

PMID- 11227836
TI  - Characteristics, management, and in-hospital mortality of acute myocardial
      infarction in the "real world" in France--data from a large unselected cohort of
      2,519 consecutive patients in a French region.
AB  - OBJECTIVE: The prospective PRIMA study (Prise en charge de l'Infarctus du
      Myocarde Aigu; management of acute MI) sought to determine characteristics,
      management, and in-hospital mortality of myocardial infarction (MI), regardless
      of age and hospital facilities, in the "real world" in a region in France.
      METHODS AND RESULTS: Data were prospectively collected in all patients with MI
      admitted in all hospitals in three departments in the Rh ne-Alpes region between
      September 1, 1993 and January 31, 1995. 2,519 patients (68% men; mean +/- SD: 68
      +/- 14 years) were included. Time from onset of symptoms to admission was < 6 h
      in 56% of the patients (median: 4 h 30 min). MI was non-Q wave in 12%. Among Q
      wave MI, location was anterior in 44%. At admission, Killip class was > 1 in 33%.
      The overall rate of thrombolysis was 36%. It was significantly higher in men than
      in women, in younger patients than in older patients, in lower Killip classes, in
      Q wave MI, and when the delay before initial medical intervention was < 6 hours.
      After age-adjustment, there was no difference between men and women for
      thrombolysis rate (odds ratio women/men: 0.92; p = 0.10). During the first 5
      days, Killip class worsened in 17%. In-hospital mortality rate was 14%.
      Multivariate analysis identified age, anterior location, presence of Q waves, and
      higher Killip classes as significant predictors of in-hospital mortality.
      CONCLUSIONS: This large unselected cohort revealed that among patients with MI in
      a French region, there was a high proportion of elderly patients, a low rate of
      thrombolysis, and a high in-hospital mortality.

PMID- 11227837
TI  - A case with Uhl's anomaly presenting with severe right heart failure.
AB  - Uhl's anomaly was first reported by Uhl in 1952 and is characterized by
      congenital partial or complete absence of right ventricular myocardium. It is a
      very rare anomaly with unknown aetiology. Associations with other congenital
      heart diseases, familial occurrency, sudden death and arrhythmia with Uhl's
      anomaly have been reported. Pathologic findings vary with the patient's age and
      severity of the right ventricular disorder. In infancy, it may occur with severe
      right-sided heart failure as well as asymptomatic cardiomegaly. Despite its
      rarity, Uhl's anomaly may be considered in patients with right ventricular
      failure due to dilated cardiomyopathy of the right ventricle. We report the case
      of six-year-old boy presenting with striking ascites due to severe right heart
      failure of Uhl's anomaly.

PMID- 11227838
TI  - Recurrent coronary stent thrombosis.
AB  - A 63-year-old woman with an acute anterior myocardial infarction was treated with
      primary stent implantation. The absence of coronary artery stenosis and an
      haematocrit of 58 were indicative of a myeloproliferative disorder and the
      diagnosis of polycythaemia vera (Vaquez' disease) was confirmed by bone marrow
      aspiration. The patient had a re-infarction 8 days later. A rescue percutaneous
      angioplasty was performed for stent thrombosis after unsuccessful thrombolysis. A
      few hours after sheath removal, a femoral artery thrombosis at the puncture side
      needed urgent thrombectomy. Finally, a second re-infarction occurred, followed by
      an irreversible cardiac arrest. Stent thrombosis is a difficult-to-treat
      complication in patients with polycythaemia vera. If this haematologic disorder
      is known, primary stent implantation for acute myocardial infarction may not be
      the first choice in these patients.

PMID- 11227840
TI  - Estimating wealth effects without expenditure data--or tears: an application to
      educational enrollments in states of India.
AB  - Using data from India, we estimate the relationship between household wealth and
      children's school enrollment. We proxy wealth by constructing a linear index from
      asset ownership indicators, using principal-components analysis to derive
      weights. In Indian data this index is robust to the assets included, and produces
      internally coherent results. State-level results correspond well to independent
      data on per capita output and poverty. To validate the method and to show that
      the asset index predicts enrollments as accurately as expenditures, or more so,
      we use data sets from Indonesia, Pakistan, and Nepal that contain information on
      both expenditures and assets. The results show large, variable wealth gaps in
      children's enrollment across Indian states. On average a "rich" child is 31
      percentage points more likely to be enrolled than a "poor" child, but this gap
      varies from only 4.6 percentage points in Kerala to 38.2 in Uttar Pradesh and
      42.6 in Bihar.

PMID- 11227839
TI  - Variance effects in the Bongaarts-Feeney formula.
AB  - Bongaarts and Feeney have recently proposed an adjusted total fertility rate to
      disentangle tempo effects from changes in the quantum of fertility. We propose an
      extension to the Bongaarts and Feeney formula that includes variance effects:
      that is, changes in the variance of the fertility schedule over time. If these
      variance effects are ignored, the mean age at birth and the adjusted total
      fertility rate are biased. We provide approximations for these biases, and we
      extend the TFR adjustment to fertility schedules with changing variance. We apply
      our method to the Swedish baby boom and bust, and show that variance effects are
      important for evaluating the relative contributions of tempo and quantum effects
      to the fertility change from 1985 to 1995.

PMID- 11227841
TI  - The impact of immigration on the internal migration of natives and immigrants.
AB  - In this paper we examine the internal migratory response, by native-born non
      Hispanic white men and foreign-born men in the United States, to recent
      immigration. Our analysis does not support the claim that natives have made a
      migratory response to recent immigration. Native-born men and foreign-born men
      were less likely to leave states that received large numbers of immigrants in the
      1980s than they were to leave other states, and native-born men had less
      propensity toward out-migration than did foreign-born men. Out-migration was most
      likely to be deterred if recent immigrants originated in Europe or Asia. Although
      native-born non-Hispanic white men showed a tendency toward out-migration if
      recent immigrants originated in Latin America or the Caribbean, this result was
      insignificant after we controlled for state economic and regional context.

PMID- 11227842
TI  - A sensitivity analysis of the Bongaarts-Feeney method for adjusting bias in
      observed period total fertility rates.
AB  - Our sensitivity analysis shows that the adjusted TFR'(t) using the formula of
      Bongaarts and Feeney (1998), which assumes an invariant shape for the fertility
      schedule, usually does not differ significantly from an adjusted TFR"(t) that
      allows the shape of the fertility schedule to change at a constant annual rate.
      Because annual changes in the shape of the fertility schedules often are
      approximately constant except in abnormal conditions, the Bongaarts-Feeney (B-F)
      method is generally robust for producing reasonable estimates of the adjusted
      TFR'(t). The adjusted TFR'(t) neither represents any real cohort experiences from
      the past nor forecasts any future trend. It merely provides an improved reading
      of the period fertility measure, which reduces the tempo distortion.

PMID- 11227843
TI  - Behavior genetic modeling of human fertility: findings from a contemporary Danish
      Twin Study.
AB  - Behavior genetic designs and analysis can be used to address issues of central
      importance to demography. We use this methodology to document genetic influence
      on human fertility. Our data come from Danish twin pairs born from 1953 to 1959,
      measured on age at first attempt to get pregnant (FirstTry) and number of
      children (NumCh). Behavior genetic models were fitted using structural equation
      modeling and DF analysis. A consistent medium-level additive genetic influence
      was found for NumCh, equal across genders; a stronger genetic influence was
      identified for FirstTry, greater for females than for males. A bivariate analysis
      indicated significant shared genetic variance between NumCh and FirstTry.

PMID- 11227844
TI  - The density of social networks and fertility decisions: evidence from South
      Nyanza district, Kenya.
AB  - Demographers have argued increasingly that social interaction is an important
      mechanism for understanding fertility behavior. Yet it is still quite uncertain
      whether social learning or social influence is the dominant mechanism through
      which social networks affect individuals' contraceptive decisions. In this paper
      we argue that these mechanisms can be distinguished by analyzing the density of
      the social network and its interaction with the proportion of contraceptive users
      among network partners. Our analyses indicate that social learning is most
      relevant with high market activity; in regions with only modest market activity,
      however, social influence is the dominant means by which social networks affect
      women's contraceptive use.

PMID- 11227845
TI  - Increasing fertility in cohabiting unions: evidence for the second demographic
      transition in the United States?
AB  - As cohabitation becomes increasingly common and accepted, one might expect the
      meaning of this arrangement to change. In some countries in Europe (e.g.,
      Sweden), as cohabitation became more prevalent, it moved from a deviant status to
      an acceptable alternative to marriage. Will the same thing happen in the United
      States? To investigate this question, I examine increases in the proportion of
      births occurring in cohabiting unions, using data from the 1987-1988 National
      Survey of Families and Households (NSFH) and the 1995 National Survey of Family
      Growth (NSFG). The standardization and decomposition procedure shows that most of
      the growth in the proportion of births to cohabitors is the result of increases
      in the proportion of women cohabiting, rather than changes in union formation
      behaviors surrounding pregnancies.

PMID- 11227846
TI  - Dimensions of women's autonomy and the influence on maternal health care
      utilization in a north Indian city.
AB  - The dimensions of women's autonomy and their relationship to maternal health care
      utilization were investigated in a probability sample of 300 women in Varanasi,
      India. We examined the determinants of women's autonomy in three areas: control
      over finances, decision-making power, and freedom of movement. After we control
      for age, education, household structure, and other factors, women with closer
      ties to natal kin were more likely to have greater autonomy in each of these
      three areas. Further analyses demonstrated that women with greater freedom of
      movement obtained higher levels of antenatal care and were more likely to use
      safe delivery care. The influence of women's autonomy on the use of health care
      appears to be as important as other known determinants such as education.

PMID- 11227847
TI  - Reconsidering mortality compression and deceleration: an alterative model of
      mortality rates.
AB  - In this research we develop a model of mortality rates that parameterizes
      mortality deceleration and compression, permits hypothesis tests for change in
      these parameters over time, and allows for formal gender comparisons. Our model
      fits mortality data well across all adult ages 20-105 for 1968-1992 U.S. white
      data, and the results offer some confirmation of findings of mortality research
      using conventional methods. We find that the age at which mortality deceleration
      begins is increasing over time, that decompression of mortality is occurring, and
      that these trends vary substantially across genders, although male and female
      mortality patterns appear to be converging to some extent.

PMID- 11227849
TI  - Esophageal candidiasis in non-immune suppressed patients in a semi-urban town,
      southern India.
AB  - OBJECTIVES: Prevalence of Esophageal Candidiasis in non-immune compromised
      patients in a semi-urban town, was investigated. Further, various investigation
      procedures to detect the candidal pathogen were compared. METHODS: A total of 933
      patients with odynophagia and dysphagia were included in this study. Upper GI
      endoscopy was performed in all these patients and biopsy specimens were taken
      from the site of lesions. Oral swabs were also taken. Both these specimens were
      analyzed for the presence of fungal pathogen through, direct microscopic
      examination and culture method. RESULTS: Among the diagnostic techniques, culture
      of biopsy in Sabouraud's media was found to be the most reliable method. Of the
      933 trialists, 61 were found to have lesions of varied degree of severity. Among
      these, 56 were positive for fungal pathogen, which was confirmed by germ tube
      test, cultural characteristics, auxanogram, etc., Candida albicans (87.5%) was
      the most predominant pathogen followed by C. tropicalis (8.9%). Men in the age
      group of 40 years and above were observed to have higher frequency of candidal
      infections compared to other groups of trialists. CONCLUSION: This investigation
      strongly suggests the possibilities of candidal infections in patients even in
      the absence of predisposing factors such as HIV infection or immune compromised
      conditions. Hence, patients with symptoms of odynophagia and dysphagia shall be
      considered for possible esophageal candidiasis.

PMID- 11227848
TI  - New African American life tables from 1935-1940 to 1985-1990.
AB  - New life tables for African Americans are presented from 1935 through 1990. They
      are based on a historical series of vital statistics data on deaths that have
      been corrected for age misreporting, on reconstructed population counts that have
      been adjusted for census underenumeration, and on births that have been corrected
      for underregistration. The new life tables show rapid mortality declines for both
      African American males and females from 1935 to 1950, and relatively steady
      reductions thereafter for females. The smaller declines in male mortality in
      young adulthood and middle age since the 1950s have led to exceptionally high
      ratios of male to female mortality at these ages. Corrections for census
      undercounts lead to higher values of life expectancy than in official life
      tables, but to less improvement over time. Official estimates of life expectancy
      at age 65 appear to be about 10% too high around 1940 but only about 1.5% too
      high in the late 1980s.

PMID- 11227850
TI  - Toxigenic saprophytic fungi in marine shellfish farming areas.
AB  - Toxigenic saprophytic fungi were isolated from samples of shellfish, sediment and
      seawater obtained from marine shellfish farming areas. The 456 strains identified
      included 12 different genera, with a clear predominance (68%) of Penicillium,
      Aspergillus, Trichoderma and Cladosporium. To assess the risk of poisoning due to
      the presence of these fungi in shellfish farming areas, the strains were cultured
      in liquid medium, filtered, and tested on larvae of Artemia salina, a small
      crustacean highly sensitive to mycotoxins. Thirty-five point five percent of the
      strains proved active with this test. This study confirms the existence of fungi
      in shellfish farming areas, as suggested by our earlier work showing that filter
      feeding shellfish accumulate toxic metabolites of fungal origin. The presence of
      fungi in the marine environment represents a real risk of poisoning through the
      consumption of contaminated shellfish.

PMID- 11227852
TI  - Incidence of allergenically significant fungal aerosol in a rural bakery of West
      Bengal, India.
AB  - The frequency of fungal spores in the air of three different sections of a rural
      bakery was analyzed using a Burkard personal slide sampler and Andersen two stage
      viable sampler. In average concentration of spores (No./m3) was 228-26770/m3 and
      concentration of viable colony forming units (CFU/m3) was 65-2061 CFU/m3.
      Dominant fungus species both culturable and nonculturable, were species of
      Aspergillus and Penicillium, Cladosporium sp., Aspergillus niger, Aspergillus
      flavus, Aspergillus fumigatus, Cladosporium cladosporioides, Penicillium citrinum
      and Alternaria alternata. Seasonal variations in the spore concentrations were
      clearly observed in case of some fungi. Total culturable mould concentration of
      different bakery sections sometimes exceeded the acceptable limit for a healthy
      indoor environment. Antigenic extracts prepared from some dominant culturable
      fungi showed high level of allergenicity in skin prick tests indicating that they
      could be responsible for allergic respiratory dysfunction of bakery workers.

PMID- 11227851
TI  - The time course of responses to intratracheally instilled toxic Stachybotrys
      chartarum spores in rats.
AB  - Stachybotrys chartarum is a fungal species that can produce mycotoxins,
      specifically trichothecenes. Exposures in the indoor environment have reportedly
      induced neurogenic symptoms in adults and hemosiderosis in infants. However,
      little evidence has linked measured exposures to any fungal agent with any health
      outcome. We present here a study that focuses on quantitatively assessing the
      health risks from fungal toxin exposure. Male, 10 week old Charles River-Dawley
      rats were intratracheally instilled with approximately 9.6 million Stachybotrys
      chartarum spores in a saline suspension. The lungs were lavaged 0 h (i.e.,
      immediately post-instillation), 6, 24 or 72 h after instillation. Biochemical
      indicators (albumin, myeloperoxidase, lactic dehydrogenase, hemoglobin) and
      leukocyte differentials in the bronchoalveolar lavage fluid and weight change
      were measured. We have demonstrated that a single, acute pulmonary exposure to a
      large quantity of Stachybotrys chartarum spores by intratracheal instillation
      causes severe injury detectable by bronchoalveolar lavage. The primary effect
      appears to be cytotoxicity and inflammation with hemorrhage. There is a
      measurable effect as early as 6 h after instillation, which may be attributable
      to mycotoxins in the fungal spores. The time course of responses supports early
      release of some toxins, with the most severe effects occurring between 6 and 24 h
      following exposure. By 72 h, recovery has begun, although macrophage
      concentrations remained elevated.

PMID- 11227854
TI  - [Correction of NO-dependent cardiovascular disorders by adaptation to hypoxia].
AB  - Spontaneously hypertensive rats (SHR-SP) were adapted to intermittent hypobaric
      hypoxia in an altitude chamber for 40 days. The adaptation to hypoxia prevented
      an excessive endothelium-dependent relaxation and hypotension characteristic of
      myocardial infarction. The adaptation also attenuated the increase in blood
      pressure and prevented impairment of the endothelium-dependent relaxation in SHR
      SP. The universal nature of the adaptation allows to use it for correcting many
      cardiovascular disorders related to diverse alterations of NO metabolism.

PMID- 11227853
TI  - The effect of the Fusarium metabolite beauvericin on electromechanical and 
      physiological properties in isolated smooth and heart muscle preparations of
      guinea pigs.
AB  - The electromechanical and -physiological effects of beauvericin were studied in
      isolated smooth and heart muscle preparations of the guinea pig. Beauvericin
      concentration-dependently decreased the force of contraction in precontracted (60
      mM KCl) terminal ilea with an IC50 of 0.86 microM, and in electrically stimulated
      (1 Hz) papillary muscles with an IC50 of 18 microM. This negative inotropic
      effect in papillary muscles was antagonised in a non-competitive way by increased
      extracellular calcium concentrations. Spontaneous activity in right atria was
      affected at concentrations > 10 microM beauvericin. The negative chronotropic
      effect was less pronounced than the negative inotropic effect. In action
      potentials of electrically driven (1 Hz) papillary muscles, 10 microM beauvericin
      significantly decreased membrane resting potential until unexcitability of the
      preparation occurred. Despite depolarisation of the membrane the maximum rate of
      rise of the action potential was not changed. The action potential duration was
      shortened, but the decrease was only significant at times to 20% and 50%
      repolarisation. These data, derived from the electrophysiological experiments,
      not only imply an effect on the calcium current as suggested by the effects on
      contractility, but also an interaction with the sodium inward and potassium
      outward currents.

PMID- 11227855
TI  - [Adaptation of the rat small intestine to ischemia].
AB  - Pre-conditioned rats underwent one cycle of intestinal ischemia/reperfusion with
      subsequent assessment of the heart remote ischemic pre-conditioning (IPC). A
      local IPC exerted an obvious protective action whereas a remote IPC was
      ineffective. The local IPC depended partially on the nitric oxide (NO) synthesis.
      L-arginine administration reduced the intestinal injury. The findings suggest
      that the ischemic pre-conditioning of intestine depends partially on the NO
      synthesis and that the remote IPC in intestine does not exist.

PMID- 11227856
TI  - [Effect of pineal peptide on parameters of the biological age and life span in
      mice].
AB  - Female CBA mice were injected with s.c. synthetic tetrapeptide Epithalon from a 6
      month age until death. The drug failed to affect the body weight or food
      consumption, physical activity or behavioural parameters. However, it slowed down
      the age-related switching off of the estrus function, decreased body temperature,
      decelerated free redical processes, prolonged the mice life span with an
      accompanying drop in spontaneous tumour incidence.

PMID- 11227858
TI  - [Effect of negative intrathoracic pressure on venous return].
AB  - In acute experiments on cats and in observations made in human subjects, an
      increase of the negative intrathoracic pressure (NIP) leads to no significant
      changes of the venous return (VR) mean values. The peak values of the VR,
      however, increased and decreased more in inspiration and expiration following a
      deep breathing as compared with the normal breathing. The NIP seems to exert no
      direct effect upon the VR.

PMID- 11227857
TI  - [Changes in the skin microvessel permeability following destruction of the
      mamillary-tegmental tract in normal and capsaicin-treated rats].
AB  - An increase in vascular permeability as measured by the Evans Blue dye leakage
      into forepaws, was observed 1 hour following the destruction of mamillo-tegmental
      tracts in rats. Ten days after capsaicin pre-treatment the destruction did not
      induce any changes of the microvascular permeability in the skin forepaws. The
      findings suggest that the descending projections of hypothalamic mamillary nuclei
      might regulate the mechanisms of the skin microvessel permeability, the action
      being mediated through capsaicinsensitive neurons of the spinal ganglion.

PMID- 11227859
TI  - [Efficacy of neurogenic and humoral stimuli in venous return in cats].
AB  - Humoral stimuli (i.v. adrenaline) proved to exert a greater effect on venous
      return in anesthetized cats than neurogenic those (electrical stimulation of
      either brain stem or femoral nerve). The part of cardiac output, however, in
      arterial blood shifts was the same. The latter finding is, probably, due to a
      discrepancy between changes occurring in the venous return and cardiac output
      caused by blood detention within the lung circulation as well as by an elevation
      of the blood pressure.

PMID- 11227861
TI  - [Arterial and venous blood flows in cats in deep respiration following
      orthostatic and antiorthostatic tilts].
AB  - In anesthetized cats, an increase in negative intrathoracic pressure following
      orthostatic and antiorthostatic tilts exerted no effects on the vena cava blood
      flow, whereas the carotid artery blood flow increased following the
      antiorthostatic tilt.

PMID- 11227860
TI  - [Effect of taurine on the microvessel exchange function and adrenergic response
      of veins and arteries in the cat skeletal muscle].
AB  - In cats anesthetized with Uretan and perfused with a constant blood volume,
      Taurine induced responses of neither arterial nor venous vessels of the skeletal
      muscle but increased the capillary filtration coefficient without any significant
      change of the capillary pressure in the skeletal muscle's microvessels. Taurine
      also increased both the constrictor and the dilatory responses of the arterial
      and venous vessels. The mechanism of the Taurine effects upon the smooth muscle
      elements of arteries and veins as well as upon proper mechanisms of capillary
      pressure control and capillary filtration coefficient, seems to be calcium
      dependent.

PMID- 11227862
TI  - [Adrenergic responses of arterial and venous vessels in the cat skeletal muscle
      in hypoxia and hypothermia].
AB  - In 12 anesthetized cats both hypoxia and hypothermia enhanced the shifts in
      arterial resistance against blood flow in response to noradrenaline and
      diminished the shifts in response to isoproterenol. Combination of both stress
      factors considerably weakened the adrenergic vasoconstriction and rather little
      affected the adrenergic vasodilatation. The findings suggest that protective
      effect of hypothermia against the background of a hypoxic stress might be a
      mechanism preventing disorders in the tissue metabolism.

PMID- 11227863
TI  - [Non-adrenergic mechanisms of inhibition of the contractile activity of the cat
      small intestine by histamine, bradykinin, and met-enkephalin].
AB  - I. a. histamine and bradykinin caused both an activation and an inhibition of
      jejunal contractile activity. The inhibitory effect was preserved after blockade
      of muscarinic cholinoreceptors, alpha- and beta-adrenoceptors, and abolished with
      the nicotinic cholinoceptor blockade. Metenkephalin inhibited the jejunal
      contractile activity after first activating it. The inhibitory effect of the
      peptide was preserved after blockade of alpha- and beta-adrenoceptors as well as
      the nicotinic cholinoceptors. The data obtained suggest that the non-adrenergic
      inhibitory effect of metenkephalin on intestinal contractions was the result of
      its depressing action on motor cholinergic neurons, whereas the inhibition of
      intestinal contractile activity with histamine and bradykinin resulted from their
      activating action on cholinergic interneurons which activate non-adrenergic
      inhibitory neurons through nicotinic cholinoceptors.

PMID- 11227864
TI  - [Dynamics of the microvessel responses in the projection areas of the rat
      somatosensory cortex].
AB  - A mosaic distribution of local cerebral blood flow was found in the rat border
      cells of the somatosensory brain cortes, as well as development of local
      functional hyperemia during whisker stimulation. The more intensive the
      stimulation the shorter were latency and amplitude of the hyperemia. The early
      phase of the hyperemia seems to be associated with neuronal factors, whereas the
      late component depended on the endothelium.

PMID- 11227865
TI  - [Capacity and exchange functions of the kidney blood vessels at various leveles
      of venous outflow].
AB  - In perfusion of the cat hemodynamically isolated kidney with a constant blood
      flow volume, responses of venous vessels to noradrenaline did not depend on the
      venous outflow pressure level and only involved a diminishing of the blood
      filling which distinguishes kidneys from other organs. The renal veins' capacity
      decreased in response to noradrenaline practically completely disappears in high
      values of the venous outflow pressure. The renal capillary filtration coefficient
      was shown to equal 0.21 +/- 0.11, whereas the effect of changes in renal vein's
      pressure on implementation of the microvessels' exchange function in determined
      by the shifts of capillary hydrostatic pressure.

PMID- 11227866
TI  - [Analysis of the striato-pallidal interactions in regulation of avoidance
      behavior].
AB  - Impairment of avoidance conditioning in the shuttle box was found in rats with
      bicuculline intrapallidal administration, as well as activation of the
      conditioning and stereotyped movements during amphetamine intrastriatal
      administration. These neuropharmacological effects upon both ganglia areas
      induced dynamic behavioural changes in the avoidance conditioning and open-field
      locomotor activity. The findings suggest involvement of neostriatalpallidal
      relationship in control of avoidance conditioning and complex behavioural acts.

PMID- 11227867
TI  - [Cell dynamics of the erythroblast islets cultured in vitro].
AB  - Comparing the cell composition of erythroblastic islets containing leukocytes
      with those cultivated in presence of erythropoietin, the mat proliferating islets
      were found to contain lymphoid cells while mature islets contained granulocytes.
      In 72 hours of cultivation the number of islets containing lymphoid cells
      increased whereas the granulocytes containing islets decreased in number.

PMID- 11227868
TI  - [Effect of initial (spontaneous) arterial pressure on systemic hemodynamic
      orthostatic responses].
AB  - In anesthetized rats, a reverse linear correlation of arterial pressure (AP)
      shifts was found within the range of initial AP over 95 mm Hg under the head-up
      tilts at 30 and 45 degrees. Within the range beneath 95 mm Hg this correlation
      was transformed into the direct one. Under 60 degrees tilt such correlation only
      occurred within the range beneath 95 mm Hg. The direction and degree of the
      arterial system responsiveness seems to depend on the tilt value as well as on
      the range of the initial AP.

PMID- 11227870
TI  - Innate and acquired resistance to African trypanosomiasis.
AB  - The review discusses the current field status of human and bovine
      trypanosomiases, and focuses on the molecular basis of innate and acquired
      control of African trypanosomes in people, cattle, and Cape buffalo.

PMID- 11227869
TI  - [Contractions of the lymphangion under low filling conditions and the absence of
      stretching stimuli. The possibility of the sucking effect].
AB  - Regulation of the function of the lymphatic pump is tightly connected to the
      degree of filling of the lymphangion. This mechanism is one of the principle ways
      that the lymphatics self-regulate lymph transport. But interpretation of the
      causes and consequences of this regulation is still far from perfect. The issue
      of whether automatism of electrical activity of the lymphatic smooth muscle cells
      or the distension of the cell membranes first causes depolarization, is a
      principal question which needs answering in order to understand the control of
      lymph transport. In our experiments with perfused isolated bovine mesenteric
      lymphangions, different values of lymph pressure were simulated. For this
      purpose, lowfrequency sinusoidal fluctuations of the input pressure were applied
      to lymphangions under conditions of regulated filling. A poor correlation was
      seen between lymph pressure fluctuations and lymphangion contractions, as well as
      between the rate of lymphangion filling and contractions. We observed stable
      spontaneous contractions of both bovine and rat mesenteric lymphangions at 0 cm
      of water intralymphatic pressure, and in the absence of distension stimuli (both
      radial and axial stretch). Under conditions of low filling, contractions of
      bovine lymphangions produced negative intralymphatic pressure and a suction
      effect. The automatism is an inherent feature of the lymphatic smooth muscle
      cells. Distension of the lymphangion modulates the electrical characteristics of
      the membranes and thus the contractile mechanisms in lymphangions.

PMID- 11227871
TI  - Effect of temperature on the infectivity of metacercariae of Zygocotyle lunata
      (Digenea: Paramphistomidae).
AB  - As a test of the energy limitation hypothesis (ELH), we predicted that
      temperature would have a significant influence on the infectivity of
      metacercariae of the digenetic trematode Zygocotyle lunata. Snails infected with
      Z. lunata were collected from ponds near Crawfordsville, Indiana, isolated at
      room temperature, and examined for the release of cercariae. Newly encysted
      metacercariae were collected and incubated 1-30 days at 1 of 5 temperatures (0,
      3, 25, 31, 37 C). Twenty-five cysts were fed to each of 5 or 10 mice per
      treatment group (temperature). At 17 days postinfection, mice were killed and
      worms were recovered; data were collected on levels of infection in each group
      and the total body area of each worm. No worms were found in mice fed cysts that
      had been held at 0 C or 37 C (after 30 days). There were no differences in
      prevalence, infectivity, or mean intensity among the 3, 25, and 31 C treatments.
      Infectivity of metacercariae incubated at 37 C for 1 day was significantly
      greater than in all other treatments, while infectivity of metacercariae in the
      37 C/15-day treatment was significantly lower than in all others. Mean body area
      of worms at 37 C/15 days was significantly greater than at other temperatures,
      suggesting density-dependent increases in growth. These results, particularly
      those from the 37 C treatments, are consistent with the ELH; infectivity was
      lower at high temperatures or when incubated for more time at 1 temperature
      (fewer energy reserves). It is suggested that microhabitat conditions experienced
      by metacercariae of Z. lunata could contribute to longer larval life, thus
      influencing this parasite's temporal dispersal.

PMID- 11227872
TI  - Persistent infection of Myxobolus cerebralis, the causative agent of salmonid
      whirling disease, in Tubifex tubifex.
AB  - The objective of this study was to quantify and determine the periodicity in the
      release of the triactinomyxon (TAM) stage of Myxobolus cerebralis, the causative
      agent of salmonid whirling disease, by its aquatic oligochaete host Tubifex
      tubifex. For this, 24 individual T. tubifex (infected as a group at 15 C) were
      examined daily for the release of M. cerebralis TAMs, and the number of
      waterborne TAMs released by each worm was quantified. The duration of the
      infection in these worms was also monitored using a polymerase chain reaction
      (PCR) diagnostic test. TAMs were first released 74 days postexposure (PE) and
      continued to be released until 132 days PE. During this period, each worm
      released on average, 1.5 x 10(3) waterborne TAMs 12 times; however, no pattern or
      periodicity was noted. The results of the PCR diagnostic tests conducted at 5, 7,
      9, and 15 mo PE were positive, and the persistent infection was confirmed at 606
      days PE (approximately 20 mo) when the remaining worms began releasing TAMs
      again. Similar results were observed in naturally infected T. tubifex, indicating
      that these worms remain infected for the duration of their natural lifespan and
      are capable of shedding viable TAMs, in temporally separate periods. These
      findings open the possibility of a seasonal periodicity in TAM release by T.
      tubifex.

PMID- 11227874
TI  - Alterations of the microcirculatory network during the clearance of epimastigote
      forms of Trypanosoma cruzi: an intravital microscopic study.
AB  - The distribution of epimastigote forms of Trypanosoma cruzi in the
      microcirculatory network and the vessel alterations were observed using an
      intravital microscopy technique. Immediately after intravenous inoculation of 2 x
      10(6) epimastigote suspension into normal mice, parasites were seen as
      circulating clumps, and their retention at some sites of the endothelium of
      venules and capillaries was observed. Injection of 2 x 10(7) and 2 x 10(8)
      parasite suspensions induced, respectively, intermittent or total stasis of
      venules and capillaries, probably via obstruction by clumping. The mobility of
      epimastigotes in the clumps indicates that parasites were alive in the lumen of
      vessels. The retention of clumps in the capillaries, although intense, could only
      be observed when labeled parasites were inoculated. These results suggest that
      the rapid clearance of epimastigote forms of T. cruzi from the blood circulation
      of mice may be due to the retention of parasites to the endothelium of venules
      and capillaries that, in turn, may facilitate phagocytosis. This may be a
      mechanism by which mice are able to eliminate epimastigote forms from the
      circulation. These findings are consistent with our previous observations showing
      that epimastigotes are not lysed by complement activation but are phagocytosed
      and destroyed by a distinct population of blood cells.

PMID- 11227873
TI  - Transplacental transmission of Toxoplasma gondii in minipigs infected with
      strains of different virulence.
AB  - Infections with the zoonotic protozoan Toxoplasma gondii during pregnancy can
      result in severe fetal infections. To investigate the use of pigs as animal
      models for congenital toxoplasmosis, tachyzoites of 5 T. gondii strains, with low
      to intermediate virulence in mice, were intravenously inoculated into pregnant
      minipig gilts. Two strains caused abortions of uninfected fetuses following
      severe disease of the mothers. One strain caused no disease in the gilts but
      slightly elevated anti-T. gondii antibodies in 2 of 9 fetuses. One strain
      produced clinical disease with 4 mummified fetuses and 2 full-term, congenitally
      infected piglets in 1 gilt and no clinical disease but elevated specific fetal
      antibodies in both piglets of the other gilt. Infection with the fifth strain
      (SVS-O14), which was considered apathogenic to both pigs and mice based on the
      clinical course of this and previous experiments, resulted in significant numbers
      of congenitally infected piglets, as indicated by production of anti-T. gondii
      antibodies in all 12 fetuses; the parasite was identified in 3 of these fetuses.
      This pattern of infection indicates that pigs infected with SVS-O14 (or a similar
      strain) are relevant animal models for studies of transplacental transmission and
      pathogenesis of congenital toxoplasmosis.

PMID- 11227875
TI  - Rallicola deckeri n. sp. (Phthiraptera: Philopteridae) from Ruddy Woodcreepers
      Dendrocincla homochroa (Passeriformes: Furnariidae) collected in Campeche,
      Mexico.
AB  - A new species of Rallicola Johnston and Harrison (Phthiraptera: Philopteridae) is
      described from lice collected from a series of Ruddy Woodcreepers Dendrocincla
      homochroa (Aves: Dendrocolaptinae) in Campeche, Mexico. Rallicola deckeri is
      easily recognized by the unique shape of the mesosome in the male and by the
      pattern of divided sternites on the female.

PMID- 11227876
TI  - Molecular phylogeny of the other tissue coccidia: Lankesterella and Caryospora.
AB  - Nearly complete sequences were obtained from the 18S rDNA genes of Eimeria
      falciformis (the type species of the genus), Caryospora bigenetica, and
      Lankesterella minima. Two clones of the rDNA gene from C. higenetica varied
      slightly in primary structure. Parsimony-based and maximum likelihood
      phylogenetic reconstructions with a number of other apicomplexan taxa support 2
      major clades within the Eucoccidiorida, i.e., the isosporoid coccidia (consisting
      of Toxoplasma, Neospora, Isospora [in part], and Sarcocystis spp.) and a second
      clade containing Lankesterella and Caryospora spp., as well as the eimeriid
      coccidia (Cyclospora, Isospora [in part], and Eimeria spp.). Our observations
      suggest that Caryospora spp. may not belong in the family Eimeriidae but rather
      may be allied with the family Lankesterellidae with which they share molecular
      and life history similarities. This may be a third lineage of coccidian parasites
      that has independently evolved a unique heteroxenous transmission strategy.

PMID- 11227877
TI  - Oxyuroids of palearctic Testudinidae--new definition for Alaeuris Seurat, 1918
      (Nematoda: Pharyngodonidae) and redescription of Alaeuris numidica (Seurat,
      1918).
AB  - The generic diagnosis of Alaeuris is emended based on the study and redescription
      of Alaeuris numidica from the cecum of Testudo graeca collected in Settat,
      Morocco and of Testudo hermanni collected in Catalonia, Spain. Scanning electron
      microscopy studies revealed that the papillae previously described as adanal are
      simple lobes because of the lack of terminal nerves, and that both preanal and
      postanal papillae are pedunculate. These new findings allowed us to emend the
      diagnosis of the genus and the species. A list of species of Alaeuris with
      biogeographic regions and hosts is provided.

PMID- 11227878
TI  - Physalopteroides arnoensis n. sp. (Nematoda: Physalopteroidea) and other
      intestinal helminths of the mourning gecko, Lepidodactylus lugubris (Sauria:
      Gekkonidae), from Arno Atoll, Republic of the Marshall Islands, Oceania.
AB  - Physalopteroides arnoensis n. sp. (Nematoda: Physalopteroidea) from the
      intestinal tract of the gecko Lepidodactylus lugubris is described and
      illustrated. Physalopteroides arnoensis is the 18th species to be assigned to the
      genus and is distinguished from other oriental species by the distribution
      pattern of caudal papillae of the male: 22 posterior subventral pedunculated
      papillae; 8 precloacal papillae in symmetrical pairs; 14 postcloacal papillae, 6
      papillae immediately postcloacal in symmetrial pairs and remaining 8 papillae
      asymmetrically placed, 3 on right, 5 on left. Other helminths found include
      Pharyngodon lepidodactylus, Hedruris hanleyae, Maxvachonia chabaudi, and larvae
      of Ascarops sp. Our review of Physalopteroides removes all subspecies
      designations; Physalopteroides minor Caballero, 1969 n. comb is proposed.

PMID- 11227879
TI  - Two new species of rhabdochonids (Nematoda: Rhabdochonidae) from freshwater
      fishes in Mexico, with a description of a new genus.
AB  - Two new nematode species, Beaninema nayaritense n. gen., n. sp. and Rhabdochona
      xiphophori n. sp., are described on the basis of the specimens recovered from the
      gall bladder and intestine of 2 fishes, Cichlasoma beani (Jordan) (Cichlidae,
      Perciformes) and Xiphophorus sp. (Poeciliidae, Cyprinodontiformes), respectively,
      from Mexico. The monotypic genus Beaninema differs from other rhabdochonid genera
      mainly in the presence of large conical teeth in the middle of the prostom.
      Rhabdochona xiphophori is characterized mainly by a unique structure of the
      prostom (presence of 6 anterior teeth; dorsal and ventral teeth unusually broad,
      with 2 lateral horns) and the shape of the deirids (bifurcated, with markedly
      long base).

PMID- 11227880
TI  - Molting of Gnathostoma doloresi (Nematoda: Gnathostomatoidea) in the definitive
      host.
AB  - Premolt, molting, and postmolt worms of Gnathostoma doloresi (Nematoda:
      Gnathostomatoidea) recovered from the stomach wall of naturally infected wild
      boars Sus scrofa leucomystax in Miyazaki, Japan, were examined morphologically.
      The only molt observed was that from the advanced third-stage to the adult stage.
      It is strongly suggested that the gnathostomes molt only once in the definitive
      host.

PMID- 11227881
TI  - Descriptions of two new species of Eimeria (Apicomplexa: Eimeriidae) and of
      Eimeria chinchillae-like oocysts from the plains vizcacha Lagostomus maximus
      (Desmarest, 1817) (Rodentia: Chinchillidae) from Argentina.
AB  - Of 163 fecal samples collected between March 1997 and February 1999 from the
      plains vizcacha, Lagostomus maximus (Rodentia: Chinchillidae), 19 (12%) were
      found to be positive for coccidia. All species are from the genus Eimeria and 2
      are described here as new. The third species is consistent with the description
      of Eimeria chinchillae De Vos and Van der Westhuizen, 1968. Sporulated oocysts of
      Eimeria lagostomi n. sp. are ellipsoidal to subspheroidal, 35.7 x 30.9 (26-36 x
      30-41), with a length:width (L/W) ratio of 1.2 (1.0-1.3), without a micropyle (M)
      or polar granule (PG), but with an oocyst residuum (OR) comprised of a round,
      compact mass of many small granules. The sporocysts are lemon-shaped, 14.2 x 10.2
      (9-11 x 11-16), with an L/W ratio of 1.4 (1.2-1.7) and have a Stieda body (SB)
      and sporocyst residuum (SR). Eimeria vizcacho n. sp. has sporulated oocysts that
      are subspheroidal, 26.4 x 23.4 (21-27 x 23-31), with an L/W ratio of 1.1 (1.1
      1.2), lack an M and OR, but have 1-2 PGs. Sporocysts are elongate-ellipsoidal,
      14.3-9.0 (8-10 x 13-15), with an L/W ratio of 1.6 (1.4-1.8), lack an SB, but have
      2 SR; the first a small mass of granules lying between the sporozoites in the
      middle or at 1 end, and the second also of many small granules, always at the
      opposite end. Sporulated oocysts of the E. chinchillae-like organism are
      ellipsoidal to subspheroidal, 20.7 x 17.5 (15-22 x 17-24) with an L/W ratio of
      1.2 (1.0-1.3), lack an M and OR, but have 0-3 PGs. Sporocysts are ellipsoidal,
      10.7-6.9 (6-8 x 8-13) with an L/W ratio of 1.55 (1.3-1.8) and have an SB and SR.

PMID- 11227882
TI  - Tetrameres (Tetrameres) megaphasmidiata n. sp. (Nematoda: Tetrameridae), a
      parasite of the two-banded plover, Charadrius falklandicus, and white-rumped
      sandpiper, Calidris fuscicollis, from Patagonia, Argentina.
AB  - Tetrameres (Tetrameres) megaphasmidiata n. sp. is described from the
      proventriculus of the two-banded plover, Charadrius falklandicus, and the white
      rumped sandpiper, Calidris fuscicollis, from Patagonia, Argentina. The new
      species shares with T. (T.) nouveli, T. (T.) paradisea, T. (T.) prozeskyi, T.
      paraaraliensis, T. (T.) cladorhynchi, and T. lobybicis the absence of the right
      spicule and the presence of 4 rows of somatic spines. Tetrameres (T.)
      megaphasmidiata n. sp. differs from the first 4 species mainly by its longer left
      spicule. The new species can be distinguished from T. (T.) cladorhynchi by the
      extension of the lateral alae, the number and arrangement of the caudal papillae,
      and the absence of polar filaments in the eggs. Tetrameres lobybicis differs from
      the new species by having shorter rows of dorsal spines and a different number
      and arrangement of the caudal papillae. This report is the first record of a
      species of Tetrameres in C. falklandicus and C. fuscicollis.

PMID- 11227883
TI  - The blood parasites of anurans from Costa Rica with reflections on the taxonomy
      of their trypanosomes.
AB  - During May 1997, specimens of 7 species of anurans, that included 5 Phrynohyas
      venulosa Laurenti, 5 Rana forreri Boulenger, 7 Rana vaillanti Brucchi, 6
      Eleutherodactylus fitzingeri Schimdt, 4 Smilisca baudinii Dumeril and Bibron, 1
      Leptodactylus melanonotus, and 3 Bufo marinus Linneaus, from the Guanacaste
      Conservation Area, Costa Rica were examined for blood parasites. Their hematozoan
      fauna included intraerythrocytic and intraleukocytic icosahedral viruses, a
      rickettsia (Aegyptianella sp.), 2 species of Hepatozoon, Lankesterella minima, 2
      unknown species of apicomplexans, 9 morphologically distinct types of
      trypanosomes, and 2 species of microfilariae. Rana vaillanti, the most aquatic
      species of frog, harbored the most species of parasites. Recent evidence
      indicates that morphological changes in the highly pleomorphic trypanosomes of
      anurans from different geographical regions have not kept pace with biochemical
      (isozyme) and molecular (DNA sequence) changes. Describing new species based
      solely on bloodstream trypomastigotes is discouraged. Additional criteria
      described herein should be applied when naming new species of anuran
      trypanosomes.

PMID- 11227884
TI  - Redescription and systematic status of Capillaria philippinensis, an intestinal
      parasite of human beings.
AB  - A redescription of the capillariid originally described as Capillaria
      philippinensis, a pathogenic intestinal parasite of humans, is provided on the
      basis of specimens collected in humans in the Philippines. The general
      morphology, particularly the structure of the male caudal end, shows that this
      species belongs to Paracapillaria Mendonca, 1963 according to the present
      classification system of capillariids; the species is transferred to
      Paracapillaria as Paracapillaria philippinensis (Chitwood, Velasquez, and
      Salazar, 1968) n. comb. Crossicapillaria n. subgen. is proposed to accommodate
      this species.

PMID- 11227885
TI  - Eimeria spp. (Apicomplexa: Eimeriidae) from the eastern chipmunk (Tamias
      striatus) in Pennsylvania with a description of one new species.
AB  - Intestinal contents of 41 eastern chipmunks (Tamias striatus) from Armstrong
      County, Pennsylvania, were examined for the presence of Eimeria spp. Three
      previously named species were identified: E. lateralis (prevalence = 9%), E.
      ovata (3%), and E. vilasi (74%); 1 new species, Eimeria tamiensis n. sp. (74%),
      is described here. This report extends the geographic ranges of the named species
      into Pennsylvania. Sporulated oocysts of E. tamiensis n. sp. are ovoid and 18.6 x
      14.5 (16-23 x 12-17) microm, with no micropyle or residuum. Sporocysts are
      ellipsoid and 8.6 x 5.4 (7-10 x 4-8) microm. with a Stieda body and granular
      residuum. Prevalences of E. lateralis and E. vilasi were similar to those
      reported previously. The differences in prevalences may be due to different life
      history strategies of high- and low-prevalence Eimeria species.

PMID- 11227886
TI  - Protospirura kaindiensis n. sp. (Spirura: Spiruridae) and other helminths from
      Pseudohydromys (Muridae: Hydromyinae) from Papua New Guinea.
AB  - One cestode and 3 species of nematodes are recorded from Pseudohydromys murinus
      and Pseudohydromys occidentalis (Muridae: Hydromyinae), from Papua New Guinea,
      for the first time. Heterakis fieldingi (Ascaridida: Heterakidea) has previously
      been known from Australia. Odilia sp. resembles Odilia praeputialis in the
      orientation of the synlophe and the number and size of ridges but differs in the
      length of spicule and lack of a praepuce. Protospirura kaindiensis n. sp.
      (Spirurida: Spiruridae) is readily distinguished from all other members of the
      genus by the number and arrangement of caudal papillae and the length of the
      spicules.

PMID- 11227887
TI  - Diphyllidean cestodes of the Gulf of California, Mexico with descriptions of two
      new species of Echinobothrium (Cestoda: Diphyllidea).
AB  - As part of a survey of parasites of elasmobranchs in the Gulf of California, a
      second and final report of the diphyllidean cestodes resulting from the survey is
      presented. Of 43 species of elasmobranchs examined for parasites, 7 (Rhinobatos
      productus, Rhinobatos leucorhynchus, Myliobatis californicus, Myliobatis
      longirostris, Urobatis halleri, Urobatis maculatus, and Rhinoptera steindachneri)
      were found to host diphyllidean cestodes, all belonging to Echinobothrium. No
      species of either of the other 2 diphyllidean genera, Dirrachybothridium or
      Macrobothridium, were discovered. A greater diversity of diphyllideans was found
      in 1996 than in 1993. Two new species, Echinobothrium hoffmanorum n. sp. and
      Echinobothrium rayallemangi n. sp. are described from the spiral intestines of U.
      maculatus and R. leucorhynchus, respectively. Echinobothrium hoffmanorum is
      unique in its possession of the following combination of characters: 19-21 apical
      hooks in each dorsoventral group, 12-22 lateral hooklets in each group, 10-17
      cephalic peduncle spines per column, 4-8 testes, 4-10 segments and eggs with a
      single filament. Echinobothrium rayallemangi is unique in its possession of the
      following combination of characters: 23 apical hooks in each dorsoventral group,
      20-23 lateral hooklets in each group, 2-5 cephalic peduncle spines per column, 4
      6 testes, and 4-6 segments. These 2 new species, together with Echinobothrium
      mexicanum and Echinobothrium fautleyae, brings the total number of diphyllideans
      known from the Gulf of California to 4. The survey of diphyllidean cestodes of
      the Gulf of California has resulted in a new host record for Echinobothrium for
      each of the host species mentioned above, with Rhinobatos and Urobatis
      representing new host genera and Urolophidae a new host family for
      Echinobothrium.

PMID- 11227888
TI  - Rhinebothrium xiamenensis n. sp. (Eucestoda: Tetraphyllidea) in Dasyatis zugei
      from the coast of Xiamen, China.
AB  - A new species of Rhinebothrium inhabiting Dasyatis zugei is reported from the
      southeast coast of China. This is the first report of Rhinebothrium from D.
      zugei. It represents a new host and a new location. The new species resembles
      Rhinebothrium corymbum by having a V-shaped ovary. It differs in the fewer loculi
      and testes numbers, longer bothrium pedicel and cephalic peduncle, larger cirrus
      pouch and vitelline follicles, and an aspinose peduncle. Rhinebothrium
      xiamenensis differs from Rhinebothrium ezuti, Rhinebothrium walga, and
      Rhinebothrium hawaiiensis by having discrete vitelline follicles, fewer loculi,
      and ovarian shape.

PMID- 11227889
TI  - Leishmanicidal activity of stearylamine-bearing liposomes in vitro.
AB  - Liposomes consisting of stearylamine (SA) and egg yolk phosphatidylcholine (PC)
      were studied for their cytotoxic activity against freshly transformed
      promastigotes and intracellular amastigotes of Leishmania donovani, the causative
      agent of visceral leishmaniasis. More than 99% of the parasites of strain AG83
      were killed within 60 min by treatment with 22 mol% SA-PC liposomes (132
      microg/ml total lipids). This was further confirmed by incubating the liposome
      treated promastigotes at 22 C for 96 hr. The killing activity of the liposomes
      progressively decreased with lowering lipid concentration. However, weak
      cytotoxic activity was still detected at 6.6 microg/ml lipids. Leishmanicidal
      activity of the liposomes became stronger with increasing SA content but was
      reduced with the incorporation of cholesterol in the liposomes. A similar
      cytotoxic effect was observed on other Indian strains of L. donovani, for example
      PKDL and DD8, as well as on species such as Leishmania donovani S1, Leishmania
      donovani infantum, Leishmania tropica, Leishmania amazonensis, and Leishmania
      mexicana. However, freshly transformed promastigotes appeared to be more
      susceptible than the ones subcultured. The strong leishmanicidal activity of SA
      PC liposomes was also demonstrated toward intracellular L. donovani amastigotes.
      The SA-bearing vesicles could effectively inhibit the growth and multiplication
      of the parasites within the macrophages. The cytolytic activity of these
      liposomes on leishmanial parasites and low toxicity on host macrophages may,
      thus, find application in the therapy of leishmaniasis.

PMID- 11227890
TI  - Detection of Plasmodium yoelii stage mRNA in BALB/c mice.
AB  - Relatively little information is available concerning the expression of parasite
      genes during the liver stage of Plasmodium infection, mostly because of low-level
      infection of host hepatocytes and the lack of purification techniques for the
      liver stage parasites. We have determined the optimal dosage of Plasmodium yoelii
      sporozoite inoculum and routes of inoculation, which are intravenous tail vein
      and the intrahepatic portal circulation. To determine which route was optimal,
      BALB/c mice were inoculated via 1 of these routes, and parasitemia was detected
      by reverse transcription polymerase chain reaction (RT-PCR) detecting both murine
      beta-actin and P. yoelii-specific 28S ribosomal RNA in the liver samples. Murine
      beta-actin was detected after 15 cycles of PCR, and its expression levels did not
      differ between treatment groups. However, P. yoelii-specific 28S ribosomal RNA
      gene product was detected after 15 cycles of PCR in animals inoculated via the
      tail vein but was not detected until 25 cycles in animals inoculated via the
      intrahepatic portal circulation. Experiments were then performed to identify the
      smallest inoculum required to initiate a liver stage infection that would yield
      sufficient parasite RNA for analysis. Inoculation with different doses of
      sporozoite inocula was followed by RT-PCR on the livers of the inoculated
      animals. The P. yoelii-specific 28S ribosomal RNA gene product was first detected
      in both treatment groups after 15 cycles, suggesting that both doses of
      sporozoite inocula provided relatively the same level of liver infection rate. We
      also have analyzed infected mouse liver for parasite-specific mRNA, which was
      detectable as early as 24 hr postinfection.

PMID- 11227891
TI  - The in vitro effects of isometamidium chloride (Samorin) on the piscine
      hemoflagellate Cryptobia salmositica (Kinetoplastida, Bodonina).
AB  - Isometamidium chloride (Samorin) is therapeutic in rainbow trout (Oncorhynchus
      mykiss) during preclinical and chronic cryptobiosis. However, the toxic mechanism
      of isometamidium on Cryptobia salmositica has not been elucidated. The objective
      of the present study was to examine the in vitro effects of isometamidium on C.
      salmositica. Under in vitro conditions, isometamidium chloride reduced the
      infectivity of C. salmositica suspended in whole fish blood. It accumulated
      rapidly in the kinetoplast (within 1 min) and caused disruption and decantenation
      of kinetoplast DNA. The in vitro cryptobiacidal activity of isometamidium was
      reduced when parasites were incubated in medium containing serum supplement,
      suggesting that isometamidium also binds to plasma proteins. Isometamidium
      altered glycoprotein receptors (epitopes) for antibodies on the surface of C.
      salmositica and thus protected some of the parasites from lysis by complement
      fixing antibodies. In vitro oxygen consumption and carbon dioxide production
      decreased in drug-exposed C. salmositica, with increased products of glycolysis,
      i.e., lactate and pyruvate, after exposure to isometamidium. This suggests that
      some C. salmositica switched from aerobic respiration to glycolysis when the
      mitochondrion was damaged by isometamidium.

PMID- 11227892
TI  - Immunoassay for viable Cryptosporidium parvum oocysts in turbid environmental
      water samples.
AB  - Cryptosporidium parvum oocysts in drinking water have been implicated in
      outbreaks of diarrheal disease. Current methods for monitoring environmental
      exposures to C. parvum only account for total number of oocysts without regard
      for the viability of the parasite. Measurement of oocyst viability, as indicated
      by an oocyst's ability to excyst, is useful because over time oocysts lose the
      ability to excyst and become noninfective. Thus, correlating the number of viable
      oocysts in drinking water with incidence and risk for disease should be more
      reliable than using the total number of oocysts. We have developed a quantitative
      assay capable of detecting low numbers of excystable, sporozoite-releasing C.
      parvum oocysts in turbid water samples. Monoclonal (CP7) and polyclonal
      antibodies have been developed against a sporozoite antigen released only during
      excystation or when the oocyst is mechanically disrupted. CP7 is specific for C.
      parvum and does not react with C. baileyi, C. muris, C. serpentis, Giardia spp.,
      Eimeria spp., or E. nieschulzi. In this assay, oocysts in the test sample are
      first excysted and then centrifuged. The soluble sporozoite antigen is captured
      by CP7 attached to a magnetic bead. The captured antigen is then detected by
      ruthenium-labeled polyclonal antibodies via electrochemiluminescence. The CP7
      viability assay can detect as few as 50 viable oocysts in a 1-ml assay sample
      with a turbidity as high as 200 Nephelometric turbidity units. This sensitive,
      turbidity-tolerant assay for oocyst viability may permit a better assessment of
      the disease risk associated with the presence of environmental oocysts.

PMID- 11227893
TI  - Treatment with agmatine inhibits Cryptosporidium parvum infection in infant mice.
AB  - Cryptosporidium parvum is an intracellular protozoan parasite that causes enteric
      infection and diarrhea in a wide range of mammalian hosts, including humans and
      economically important livestock species. There are no effective vaccines or drug
      treatments available for cryptosporidiosis. Cryptosporidium parvum utilizes a
      unique metabolic pathway for the synthesis of polyamines, forming agmatine as an
      intermediary metabolite. We treated infant mice with oral doses of agmatine for 2
      days before, the day of, and 5 days following experimental infection with C.
      parvum. Mice treated with agmatine were significantly less infected with C.
      parvum than were control mice receiving phosphate-buffered saline. Mice treated
      with agmatine only on the day of experimental infection with C. parvum were also
      significantly less infected than were control mice. These data suggest that
      exogenous agmatine alters the metabolism of C. parvum sufficient to interfere
      with its ability to colonize the mammalian intestine.

PMID- 11227894
TI  - First blood meal of Ctenocephalides canis (Siphonaptera: Pulicidae) on dogs: time
      to initiation of feeding and duration.
AB  - Two experiments were conducted on dogs to evaluate interval to initiation and
      duration of the first blood meal of Ctenocephalides canis (Curtis). Percentage of
      fed male and female fleas was calculated for fleas held on dogs for 5, 15, 30, 60
      min, 6, and 24 hr. Duration of first blood meal was also measured for individual
      fleas confined on dogs. When fleas were free in the hair coat, 21.2% had begun
      blood feeding within 5 min. After 1 hr, 72.5% of fleas had fed. After 6 hr, 95.2%
      of males and 100% of females had taken a blood meal, and 24 hr after deposition
      all fleas had fed. There was no significant difference between the 2 sexes. The
      mean delay between deposition and biting for fleas that began feeding within 15
      min was 2 min 52 sec +/- 3 min 2 sec for female fleas and 3 min 8 sec +/- 2 min
      45 sec for males. The mean duration of female and male meals was 5 min 3 sec +/-
      3 min 41 sec and 6 min 9 sec +/- 6 min 8 sec, respectively. There was no
      significant difference between the 2 sexes. The dog flea took its blood meal on
      dogs more slowly than the cat flea did on cats; this meal was significantly
      longer for Ctenocephalides felis felis (Bouche) than for C. canis.

PMID- 11227895
TI  - Oocyst shedding by cats fed isolated bradyzoites and comparison of infectivity of
      bradyzoites of the VEG strain Toxoplasma gondii to cats and mice.
AB  - Infectivity of bradyzoites of the VEG strain of Toxoplasma gondii was compared in
      cats and mice. For this, tissue cysts were separated from brains of infected mice
      using a Percoll gradient, and bradyzoites were released by incubation in acidic
      pepsin solution. After filtration through a 3-microm filter, bradyzoites were
      counted and diluted 10-fold in RPMI tissue culture medium. Dilutions estimated to
      have 1, 10, 100, and 1,000 bradyzoites were fed to cats and inoculated into mice,
      orally or subcutaneously (s.c.). Three experiments were performed. In experiment
      1, 2 of 2 cats fed 1,000 bradyzoites, 1 of 2 cats fed 100 bradyzoites, 1 of 4
      cats fed 10 bradyzoites, and 1 of 4 cats fed 1 bradyzoite shed millions of
      oocysts; 1,000 bradyzoites were infective to all 4 inoculated mice s.c. but not
      to 4 mice inoculated orally, and 100 bradyzoites were infective to 2 of 4 mice
      injected s.c. but not to 4 mice inoculated orally. All 16 mice (8 oral, 8 s.c.)
      injected with 1 or 10 bradyzoites were negative for T. gondii. In experiment 2, 1
      of 4 cats fed 10 counted bradyzoites shed oocysts; the same inocula were not
      infective to 4 mice injected s.c. In experiment 3, 3 of 4 cats fed 1,000
      bradyzoites shed oocysts and the inocula were infective to 10 of 10 mice s.c. and
      4 of 10 mice orally; 4 of 4 cats fed 100 bradyzoites shed oocysts and the inocula
      were infective to 6 of 10 mice s.c. and 0 of 10 mice orally; 10 bradyzoites were
      not infective to cats and mice. Results indicate that bradyzoites are more
      infective to cats than to mice, and cats can shed millions of oocysts after
      ingesting just a few bradyzoites.

PMID- 11227896
TI  - Disseminated toxoplasmosis in magpie geese (Anseranas semipalmata) with large
      numbers of tissue cysts in livers.
AB  - Fatal disseminated Toxoplasma gondii infection was diagnosed in 2 captive magpie
      geese (Anseranas semipalmata) from a zoo in Texas. Both geese died suddenly,
      without apparent clinical signs. Lesions associated with T. gondii tachyzoites
      were seen in lungs, pancreas, liver, adrenals, bursa of Fabricius, spleen, brain,
      and kidneys. Toxoplasmic pneumonia and hepatitis were considered to be the
      primary cause of death. An unusual feature was the presence of numerous tissue
      cysts in hepatocytes of both geese. The diagnosis was confirmed
      immunohistochemically. Antibodies to T. gondii were found in 2 of 11 other geese
      from the zoo examined using the modified agglutination test. This is the first
      report of T. gondii infection in magpie geese (Anseranas semipalmata).

PMID- 11227897
TI  - Effects of diet on the development of Schistosoma mansoni in Biomphalaria
      glabrata and on the neutral lipid content of the digestive gland-gonad complex of
      the snail.
AB  - In a previous study, when the snail Biomphalaria glabrata was infected with
      Schistosoma mansoni and maintained on a diet of hen's egg yolk, it produced fully
      developed cercariae in about one-half the time taken by snails fed Romaine
      lettuce. Increased lipids were also noted in the snails fed the yolk diet. The
      purpose of the present study was to further investigate nutritional effects of a
      high-lipid diet on larval schistosome development and to reexamine the time to
      cercarial patency in infected snails maintained on either the yolk or lettuce
      diet and to use high-performance thin-layer chromatography (HPTLC) to analyze the
      neutral lipids in the digestive gland-gonad complex (DGG) of snails maintained on
      both diets. Infected snails maintained at 26 C and fed either diet produced fully
      developed cercariae by 4 wk postinfection (PI). Likewise, infected snails
      maintained at 23 C and fed either diet produced fully developed cercariae by 6 wk
      PI. The contention that the yolk diet enhanced the time to cercarial patency was
      not confirmed. The HPTLC analysis of neutral lipids showed that the DGG of
      infected snails fed the yolk diet contained significantly greater amounts of free
      sterols and cholesteryl esters but not triacylglycerols than that of the infected
      snails fed the lettuce diet.

PMID- 11227898
TI  - Relevance of Cryptosporidium parvum hsp70 mRNA amplification as a tool to
      discriminate between viable and dead oocysts.
AB  - Two mRNA extraction methods were compared in this study to clarify the
      discrepancies found between authors regarding the presence of mRNA in inactivated
      Cryptosporidium parvum oocysts. Cryptosporidium parvum heat shock protein 70
      (hsp70) mRNA extraction was performed by using oligo(dT)20-labeled magnetic beads
      or by incubating oocyst lysates with DNase I. Significant differences in mRNA
      recovery rates between these 2 techniques were observed when working on
      inactivated oocysts. We consistently detected hsp70 mRNA in oocysts heated at 60
      C for 30 min and oocysts incubated in 10% formalin for 2 hr when using DNase I in
      the mRNA extraction procedure. In contrast, no mRNA was detected in such oocysts
      when magnetic beads were used for the mRNA extraction. The selective capture of
      long poly-A tail mRNA, when using oligo(dT)20-labeled magnetic beads, is proposed
      in this paper for explaining the discrepancies observed between the two mRNA
      extraction methods compared in this study. DNA decay in inactivated and aging
      oocysts makes quantitative polymerase chain reaction a potential alternative
      technique for assessing C. parvum oocyst viability status in environmental
      samples.

PMID- 11227899
TI  - Seroprevalence of Toxoplasma gondii in elephants (Elephus maximus indicus) in
      Thailand.
AB  - Serum samples from captive 156 elephants (Elephus maximus indicus) from Thailand
      were examined for antibodies to Toxoplasma gondii using the modified
      agglutination test (MAT) and the latex agglutination test (LAT). Antibodies to T.
      gondii were found in 45.5% of 156 elephants by MAT (> or = 1:50) and 25.6% of 156
      elephants by LAT (> or = 1:64). This is the first report of T. gondii infection
      in E. maximus indicus from Asia.

PMID- 11227900
TI  - An empirical model of the optimal timing of reproduction for female amphipods
      infected by trematodes.
AB  - Life-history theory predicts that hosts should reproduce when first infected by
      parasites if hosts are capable and if parasites have a lower cost on current than
      on future reproduction of hosts. We constructed an empirical model to explore
      fitness of females of the intertidal amphipod Corophium volutator that reproduced
      soon versus long after infection by the trematode Gynaecotyla adunca. For
      uninfected females, the optimal time to reproduce was at their maximum body
      length. However, for females infected by low or high intensities of trematode
      metacercariae, reproductive potential (realized fecundity) was highest for
      females that mated immediately after becoming infected. Even after removing a
      high cost of delaying reproduction for infected amphipods (high likelihood of
      depredation by sandpipers, which are final hosts of G. adunca), realized
      fecundity remained highest if reproduction occurred immediately following
      infection by trematodes. Results from our model support the view that early
      reproduction of female amphipods following infection by G. adunca is an adaptive
      life-history response to parasitism.

PMID- 11227901
TI  - Analysis of the systematic relationships among ticks of the genera Rhipicephalus
      and Boophilus (Acari: Ixodidae) based on mitochondrial 12S ribosomal DNA gene
      sequences and morphological characters.
AB  - A portion of mitochondrial 12S rDNA sequences (337-355 base pairs) and 63
      morphological characters of 36 hard-tick species belonging to 7 genera were
      analyzed to determine the phylogenetic relationships among groups and species of
      Rhipicephalus and between the genera Rhipicephalus and Boophilus. Molecular and
      morphological data sets were first examined separately. The molecular data were
      analyzed by maximum parsimony (MP), maximum likelihood, and neighbor-joining
      distance methods; the morphological data were analyzed by MP After their level of
      congruence was evaluated by a partition homogeneity test, all characters were
      combined and analyzed by MP. The branches of the tree obtained by combining the
      data sets were better resolved than those of the trees inferred from the separate
      analyses. Boophilus is monophyletic and arose within Rhipicephalus. Boophilus
      species clustered with species of the Rhipicephalus evertsi group. Most of the
      clustering within Rhipicephalus was, however, consistent with previous
      classifications based on morphological data. Morphological characters were traced
      on the molecular reconstruction in order to identify characters diagnostic for
      monophyletic clades. Within the Rhipicephalus sanguineus complex, the sequences
      of specimens morphologically identified as Rhipicephalus turanicus were
      characterized by a high level of variability, indicating that R. turanicus-like
      morphology may cover a spectrum of distinct species.

PMID- 11227902
TI  - Testosterone depresses innate and acquired resistance to ticks in natural rodent
      hosts: a force for aggregated distributions of parasites.
AB  - The effects of testosterone on acquired resistance to ticks, Ixodes ricinus, in
      their natural rodent hosts (voles, Clethrionomys glareolus, and wood-mice,
      Apodemus sylvaticus) were investigated by manipulating testosterone levels and
      exposing the hosts to repeated tick infestations. Testosterone reduced both
      innate and acquired resistance to tick feeding. During primary infestations,
      attachment rates were higher on rodents with high testosterone levels than on oil
      implanted controls. Successive infestations on voles were accompanied by a
      decrease in tick feeding success and survival, but this decrease was
      significantly greater in ticks fed on control voles than in those fed on voles
      implanted with testosterone. When reduced feeding success had been induced,
      either by vaccination with tick salivary gland extract or by 4 successive
      infestations, implantation with testosterone partially reversed the acquired
      resistance. These effects of testosterone will generate heterogeneities within
      the rodent population with respect to tick distribution and microparasite
      transmission. The lowest innate and acquired resistance to tick feeding occurs in
      that fraction of the host population, i.e., sexually active males, most actively
      involved in the transmission of both Babesia microti and Borrelia burgdorferi
      s.l.

PMID- 11227903
TI  - Characterization of the laminated layer of in vitro cultivated Echinococcus
      vogeli metacestodes.
AB  - The metacestode (larval) stages of the cestode parasites Echinococcus vogeli and
      E. multilocularis were isolated from the peritoneal cavity of experimentally
      infected C57BL/6 mice and were cultured in vitro for a period of up to 4 mo under
      conditions normally applied for the in vitro cultivation of E. multilocularis
      metacestodes. In contrast to E. multilocularis, E. vogeli did not exhibit
      extensive exogenous budding and proliferation but increased in size with a final
      diameter of up to 10 mm. Most metacestodes contained protoscoleces, singly or in
      groups, either associated with brood capsules or growing directly out of the
      germinal layer. Each individual metacestode was covered by an acellular
      translucent laminated layer that was considerably thicker than the laminated
      layer of E. multilocularis metacestodes. The ultrastructural characteristics,
      protein content, and carbohydrate composition of the laminated layer of in vitro
      cultivated E. vogeli and E. multilocularis were assessed using transmission
      electron microscopy, lectin fluorescence labeling, and lectin blotting assays.
      The laminated layer of E. vogeli is, as previously described for E.
      multilocularis metacestodes, largely composed of N-acetyl-beta-D-galactosaminyl
      residues and alpha- and beta-D-galactosyl residues, as well as of the core
      structure of O-linked carbohydrate chains, N-acetylgalactosamine-beta-1,3
      galactose. However, in contrast to E. multilocularis, N-linked glycopeptides and
      alpha-D-mannosyl and/or glucosyl residues were also associated with the laminated
      layer of E. vogeli. The laminated layer from both species was isolated from in
      vitro cultivated metacestodes, and the purified fractions were comparatively
      analyzed. The protein:carbohydrate ratio (1:1) was similar in both parasites;
      however, the protein banding pattern obtained by silver staining following sodium
      dodecyl sulfate polyacrylamide gel electrophoresis suggested intrinsic
      differences in protein composition. A polyclonal antiserum raised against the E.
      multilocularis laminated layer and a monoclonal antibody, G11, directed against
      the major E. multilocularis laminated layer antigen Em2 did not cross-react with
      E. vogeli, indicating distinct compositional and antigenic differences between
      these 2 parasites.

PMID- 11227904
TI  - Sensory neuroanatomy of a passively ingested nematode parasite, Haemonchus
      contortus: amphidial neurons of the third-stage larva.
AB  - The sensory neuronal ultrastructure of the amphids of the infective larva (L3) of
      Haemonchus contortus was analyzed, compared, and contrasted with that of the
      first-stage larva (L1). As in L1, each amphid of the L3 is innervated by 12
      neurons. Thirteen ciliated dendritic processes of 10 neurons, 3 with double
      processes, lie in each amphidial channel. The dendritic process of each finger
      cell neuron ends in a large number of digitiform projections or "fingers," many
      more than in the L1. Processes of another pair of specialized neurons, probable
      homologs of wing cells in Caenorhabditis elegans, extend into the extreme
      anterior tip of the larva; they are much longer than those in L1. In L3, the
      neurons exit through the posterior wall of the amphidial chamber individually
      rather than in a bundle, as in L1. Cell constancy between L1 and L3 was
      confirmed, and the neurons were individually identified. Significant neuron
      specific variations, presumably related to functional differences between the 2
      stages were observed. In contrast, species-specific differences are surprisingly
      small. Haemonchus contortus is closely related to hookworms and has amphidial
      structure nearly identical to that in hookworms and similar to that in C.
      elegans, to which it is also closely related.

PMID- 11227905
TI  - Characterization of Otostrongylus circumlitus from Pacific harbor and northern
      elephant seals.
AB  - Otostrongylus circumlitus (Railliet, 1899) from Pacific harbor seals (Phoca
      vitulina richardsi) and northern elephant seals (Mirounga angustirostris) were
      examined using morphological and molecular methods to determine whether northern
      elephant seals along the central California coast are infected by the same
      species of Otostrongylus as are Pacific harbor seals in the same area. Fixed
      nematodes were examined and measured using light microscopy. The polymerase chain
      reaction (PCR) was used to amplify and sequence the second internal transcribed
      spacer (ITS-2) and D3 expansion (26S) regions of ribosomal DNA of O. circumlitus
      from Pacific harbor and northern elephant seals. The ITS-2 region was also
      amplified from Parafilaroides sp. from the Pacific harbor seal, northern elephant
      seal, and California sea lion (Zalophus californianus) and used for restriction
      fragment length polymorphism (RFLP) analysis. Morphologically, it was not
      possible to distinguish O. circumlitus from Pacific harbor and northern elephant
      seals, and over a consensus length of 443 base pairs (bp) for ITS-2 and 321 bp
      for D3 the sequences of O. circumlitus from both hosts were identical. With the
      PCR-RFLP assay, it was possible to distinguish O. circumlitus from Parafilaroides
      sp. The results suggest that O. circumlitus is the same species in Pacific harbor
      and northern elephant seals, and molecular methods make it possible to
      distinguish this nematode from related nematodes.

PMID- 11227906
TI  - Biparental mitochondrial DNA inheritance in the parasitic trematode Schistosoma
      mansoni.
AB  - The maternal inheritance of mitochondrial DNA (mtDNA) in eukaryotic organisms
      occurs because of the selective destruction of paternal mtDNA molecules that may
      be present in the zygote. The elimination of sperm mtDNA is less efficient in
      interspecific crosses, and biparental inheritance of mtDNA has been observed in a
      variety of species. Because interspecific crosses are likely to be extremely rare
      in nature, parental inheritance of mtDNA has been deemed of little relevance to
      population genetics. The mtDNA of the parasitic trematode Schistosoma mansoni was
      examined for its utility in addressing epidemiological questions related to the
      transmission and spread of schistosomiasis. Prior to embarking on such
      experiments, we sought to confirm the mode of inheritance of this molecule using
      the highly polymorphic mtDNA minisatellite as a marker. In 3 separate crosses,
      mtDNA apparently identical to paternal DNA was observed in some individuals of
      the F2 and F3 generations. These observations thus suggest the intraspecific
      paternal inheritance of mtDNA across multiple generations in Schistosoma mansoni.

PMID- 11227907
TI  - Analysis of the humoral responses of Toxoplasma gondii-infected cats using
      immunofluorescent assays with tachyzoite, bradyzoite, and gametogenic stages.
AB  - We investigated levels of Toxoplasma gondii specific antibodies present in sera,
      intestinal secretions, and fecal extracts obtained from cats following primary
      and challenge infections. Antibodies specific to T. gondii tachyzoites,
      bradyzoites, sporozoites, and enteroepithelial stages were detected by indirect
      immunofluorescence assay. Enteroepithelial stage-specific antibodies were
      detected in serum as early as 2 wk after infection, whereas antibodies from
      intestinal secretions did not appear until 3 wk following infection. The T.
      gondii-specific IgG and IgA antibodies were present in serum, but only specific
      IgA antibodies were detected in the intestinal secretions. Serum IgG bound to
      tachyzoites, bradyzoites, sporozoites, and enteroepithelial stages of T. gondii,
      whereas serum IgA bound strongly to enteroepithelial stages but only weakly to
      tachyzoites and bradyzoites. IgA from intestinal secretions bound to antigens on
      all enteroepithelial stages and the distal tips of sporozoites and bradyzoites
      but did not bind to tachyzoites. IgA present in fecal extracts also bound to
      enteroepithelial stages of T. gondii. Toxoplasma gondii infection in cats induces
      the production of antibodies that bind with all forms of the parasite, including
      the enteroepithelial stages. Comparison of the staining patterns of T. gondii
      stages for serum and intestinal secretion IgA indicated differences. Thus, the
      intestinal antibody immune response may be uniquely focused on the intestinal
      stages relative to the circulating antibodies, resulting in a
      compartmentalization of the humoral response.

PMID- 11227908
TI  - Evidence for the emergence of a type-1-like immune response in intestinal mucosa
      of calves recovering from cryptosporidiosis.
AB  - This study was undertaken to characterize the mucosal response to Cryptosporidium
      parvum in infected calves that had recovered from diarrhea. Flow cytometric
      surface phenotypes of lamina propria lymphocyte (LPL) suspensions from infected
      calves and age-matched controls revealed the presence of a significantly larger
      proportion of CD25+ LPL in infected calves than in controls. Freshly isolated LPL
      from infected calves expressed more iNOS and interferon (IFN)-gamma than did
      controls. Infected calves excreted IgG1 and IgG2 isotype antibodies to C. parvum
      p23 by the end of the experiment. Moreover, immunohistochemistry of ileal
      sections revealed the presence of IgG1+ and IgG2+ B lymphocytes in the villi and
      IgG1+ but not IgG2+ B lymphocytes in continuous Peyer's patch nodules. These data
      are consistent with the emergence of a type-1-like mucosal immune response in
      terminal ileal mucosa as calves recover from cryptosporidiosis.

PMID- 11227909
TI  - Five cases of Diphyllobothrium nihonkaiense infection with discovery of
      plerocercoids from an infective source, Oncorhynchus masou ishikawae.
AB  - Five persons from 2 families residing at Miyama Town, Mie Prefecture, Japan,
      ingested fresh raw fish Oncorhynchus sp. on 9 May 1999 that was caught at Owase
      district in Mie. They all expelled diphyllobothriid cestodes 11-37 days after
      ingesting the fish. The parasites were morphologically identical to
      Diphyllobothrium nihonkaiense Yamane et al., 1986. Five plerocercoids were
      detected from a portion of the fish. Nucleotide sequence of a region of the
      cytochrome c oxidase subunit I gene of mitochondrial DNA from an adult worm was
      identical with that from the plerocercoid. The fish was identified as
      Oncorhynchus masou ishikawae according to the nucleotide sequence of the nuclear
      ribosomal second internal transcribed spacer region II gene. This is the first
      record of D. nihonkaiense plerocercoids from O. m. ishikawae.

PMID- 11227911
TI  - Newer and alternative non-steroidal treatments for asthmatic inflammation.
AB  - Although most patients with asthma can be effectively managed with minimal
      toxicity using available treatments, some patients are relatively resistant to
      treatment or are at risk for adverse effects from treatment, such as high-dose
      systemic corticosteroids. In considering new or alternative therapeutic
      candidates for asthma treatment, those possessing anti-inflammatory properties
      are of greatest interest because inflammation is recognized as having central
      importance in the pathogenesis of persistent asthma. Of non-steroidal agents that
      have well-established positions in asthma treatment, nedocromil and cromolyn
      possess significant anti-inflammatory effects, and theophylline and beta agonists
      possess some anti-inflammatory effects of potential relevance to asthma. In
      addition, there are a number of newer or alternative therapies that have
      theorized or demonstrated anti-inflammatory effects in asthma, including
      leukotriene modifier agents, anti-IgE, gold, nebulized lidocaine, cyclosporine,
      intravenous immunoglobulin, methotrexate, hydroxychloroquine, dapsone, and
      troleandomycin. This review summarizes available data about these agents for
      asthma, focusing on their putative or proven mechanisms of action, evidence for
      clinical benefit, and their potential role as corticosteroid sparing agents, and
      principal toxicities. The review also discusses factors that confound assessment
      of the clinical benefit of agents in asthma, including variability in the natural
      history of asthma, heterogeneity of airway inflammation, and varying responses to
      treatment in different subsets of asthmatics.

PMID- 11227910
TI  - Asthma in the female: hormonal effect and pregnancy.
AB  - Data support an increase in adverse outcomes in the pregnant woman with asthma,
      particularly those who are poorly controlled. Additionally, pregnancy is
      recognized to influence the course of asthma. Hormonal and physiologic changes
      are felt to direct the eventual course and outcome, but their roles are
      incompletely understood. Because of the potential for life-threatening
      consequences to mother and fetus, aggressive asthma management, as in the
      nongravid female, is recommended. Therapy may include controller agents such as
      cromolyn, beclomethasone, and the newer inhaled steroids. The newer
      antileukotriene agents may have a role in some patients. Reliever therapy with
      short-acting B2 agonists and, if needed, oral corticosteroids are indicated for
      acute exacerbations. Because of the potential for maternal and fetal harm, close
      monitoring of mother and child is essential.

PMID- 11227912
TI  - Neural-epithelial cell interplay: in vitro evidence that vagal mediators increase
      PGE2 production by human nasal epithelial cells.
AB  - During inflammatory states, airway epithelial cells are stimulated by various
      proinflammatory mediators to synthesize paracrine mediators including
      prostaglandin E2, which likely contributes to the recurrence of allergic
      inflammation. We studied the effects of acetylcholine (ACh) and substance P (SP)
      on PGE2 release because these two neuromediators are widely involved in airway
      inflammation, e.g., to trigger mucosal vasodilation and plasma exudation. PGE2
      release was studied at baseline and after addition of ACh and SP (10(-10) to 10(
      7) M) in primary cultures of human nasal epithelial cells from control mucosa,
      inflammatory non-atopic mucosa, and inflammatory atopic mucosa. The mediators'
      effects on COX 2 mRNA were assessed by Northern blotting. We also tested the
      effect of atropine and SR140333, inhibitors of ACh and SP, respectively. The
      spontaneous release of PGE2 was about three times higher in cells from atopic
      subjects. ACh and SP markedly increased PGE2 release (by more than 1.5 times) and
      this effect was similar whether the sampled tissues were inflammatory or not. In
      cells from atopic subjects this neuromediator effect led to a fivefold increase
      in PGE2 release, as compared to baseline production by cells from control mucosa.
      This stimulation of PGE2 release by neural mediators was inhibited by specific
      antagonists. ACh and SP increased COX 2 mRNA in the three groups. Thus,
      neuromediators can bolster PGE2 production in the airway, likely reinforcing
      inflammation. In conclusion, these data provide evidence that the interplay of
      nerve fibers and airway epithelial cells is likely important in inflammatory
      conditions as, e.g., allergy and asthma.

PMID- 11227913
TI  - Therapeutic targets in allergic eye disease.
AB  - The objective of this article is to provide an overview of the present state of
      treatment of ocular allergy. Immuno-ophthalmology arose in the portion of this
      past century when investigators uncovered the uniqueness of the lens proteins and
      that it could induce an immunological response otherwise know as
      phacoanaphylaxis. Further studies have shown many similarities between the eye
      and other organ systems, but one of the most profound problems was the spring
      "catarrh" that involved the eyes and nose, i.e., rhinoconjunctivitis. Treatment
      over the past 10 years has expanded with the better understanding of the allergic
      response at the conjunctival surface. Allergen immunotherapy remains a
      cornerstone of treatment. In fact, the very first report of the use of
      immunotherapy in 1911 "measured the patient's resistance during experiments ...
      of pollen extracts to excite a conjunctival reaction" (Noon L, and Cantar BO,
      Lancet 1572-1573, 1911).

PMID- 11227915
TI  - Complementary medicine for the allergist.
AB  - The objective of this article is to provide a historical overview of the present
      state of complementary and alternative medicine (CAM) in the treatment of atopic
      disorders. The evolution of medicine in the United States has been in flux with
      the advent of newer technologies, new designs in managed care, and integrating
      the cultural differences into a complex multidisciplinary health care delivery
      process. There have been several herbal modalities that contain various anti
      allergy and asthma components with effects on bronchodilation, congestion,
      pulmonary function tests, and antagonism of asthma mediators such as histamine
      and PAF, corticosteroid levels, and clearance of mucus. In the field of allergy,
      asthma, and immunology, the popularity of CAM is more widespread than other
      common chronic medical problems. Overall, CAM use has created a $15-billion-a
      year industry in dietary supplements alone. This has been especially fueled by
      the deregulation of the "herbal" industry by the congressional passage of the
      Dietary Supplement Health and Education Act of 1994. It would appear that our
      specialty would clearly benefit from expanding its knowledge base about these
      entities because "allergies" are high on the list of patients seeking CAM. This
      will prepare us to better coordinate the future possibilities and to "doctor"
      (i.e., teach) our patients about the risks and benefits of these modalities.

PMID- 11227914
TI  - The role of the allergist in Lyme disease.
AB  - The allergist may frequently be involved with cases of Lyme disease. There are at
      least three reasons for this. First, the major symptom is often a rash that
      brings into the differential diagnosis several diseases that the allergist is
      likely to have expertise in; therefore, the allergist's role as a diagnostician
      is very important. The second reason is that the Borrelia burgdorferi (Bb)
      infection is treated with antibiotics and the patients may frequently develop
      reactions that may be immune-mediated. The allergist's expertise in diagnosis and
      management of allergic reactions is important. The third reason is that there is
      no established laboratory diagnostic test so that the clinician must use the
      existing tests, most often serologic, with their limitations, in the context of a
      history and physical. The allergist as an immunologist can be very helpful in the
      proper interpretation of the test results. The differential of the rash and the
      immune response to the infecting agent is described.

PMID- 11227916
TI  - Allergy to olive pollen: a study of four family members.
AB  - We describe four family members with respiratory and dermatological
      manifestations of olive pollen allergy. The purpose of this study was 1) to
      investigate whether these patients' sera react to the same or different olive
      allergens, and 2) to identify common HLA class II antigens.

PMID- 11227917
TI  - Are there any links between Hop Japanese pollen and other weed pollens or food
      allergens on skin prick tests?
AB  - Recent investigations suggest that the importance of Hop Japanese pollen, which
      has been known as one of the major causative weed pollens, is increasing in this
      country. There have been few data dealing with the allergenic relationship
      between Hop J pollen and other food or inhalant allergens. Among 2909 patients
      who visited the Allergy Clinic of Ajou University Hospital, Suwon, Korea, 471
      patients sensitized to Hop J, mugwort, or ragweed pollens on skin-prick test were
      enrolled. Positive rates to common inhalant or food allergens and their
      allergenic relationships with other pollens or food allergens were analyzed based
      upon skin-prick test results. The positive rates to sunflower, fat hen, nettle,
      grass (Bermuda, Orchard) and tree (alder, birch, and poplar) pollen were
      significantly higher in those sensitized to Hop J pollen than in those of
      negative responders (p < 0.05, respectively). No significant associations were
      noted with ragweed or mugwort pollen (p > 0.05, respectively). In regard to food
      related allergens, an association was noted between Hop (Humulus lupulus) or
      celery allergens in those sensitized to Hop J pollen (p < 0.05, respectively).
      Hop J pollen may have possible links with celery, Hop, and sunflower pollens on
      skin-prick test. Further in vitro investigations will be needed to evaluate the
      possibility of cross-reacting components between them.

PMID- 11227918
TI  - Asthma among the famous. Wilhelm Grimm (1786-1859) German philologist and
      folklore author.

PMID- 11227919
TI  - Seasonal variability of non-specific bronchial responsiveness in asthmatic
      patients with allergy to house dust mites.
AB  - The aim of the study was to assess the seasonal variability of non-specific
      bronchial responsiveness to methacholine in allergic asthma. One hundred sixty
      five patients (83 male and 82 female) entered the study: 86 subjects (group A)
      with allergy exclusively to mites and 79 (group B) with concomitant allergy to
      pollens, e.g., "Graminae" and "Parietaria." Inclusion criteria were the absence
      of sensitization to other allergens, no smoking habit, withdrawal from steroids,
      bronchodilators, sodium cromoglycate, and antihistamines for at least four weeks
      before enrollment, FEV1 > 70% of the predicted value, and absence of other
      respiratory diseases and of upper and lower respiratory tract infections for at
      least one month before the methacholine challenge. None of the patients had been
      previously treated with specific immunotherapy. Subjects of each group (A and B)
      underwent methacholine challenge at first visit and were divided into four
      subgroups according to the period when the challenge was performed. Subgroups A1
      and B1 performed the challenge in December, January, and February; subgroups A2
      and B2 in March, April, and May; subgroups A3 and B3 in June, July, and August;
      subgroups A4 and B4 in September, October, and November. PD20 values were
      expressed as the natural logs of the cumulative dose of methacholine causing at
      least a 20% fall in FEV1. Statistical analysis was carried out using multiple
      group analysis and Student's t-test. Results showed that the highest non-specific
      bronchial responsiveness was observed in autumn (ln PC20 = 4.54 +/- 1.51) in
      patients allergic to mites only (group A), and in summer (ln PC20 = 4.72 +/-
      2.11) in those of group B. Multiple group analysis showed statistical significant
      differences between subgroups within each group (group A, p = 0.039; group B, p <
      0.001). In patients allergic exclusively to house dust mites (group A), multiple
      comparisons and Student's t-test showed statistically significant differences
      between non-specific bronchial responsiveness (NSBR) assessed in autumn and those
      of other seasons (winter, p = 0.002; spring, p < 0.001; summer, p = 0.082). These
      results confirm that the level of allergen exposure may influence NSBR. Mite
      allergic patients showed an increase of NSBR in autumn, possibly as a consequence
      of higher indoor mite concentration. However, mite- and grass-allergic patients
      had wider variations of NSBR, possibly reflecting changes in seasonal pollen
      concentration.

PMID- 11227920
TI  - Chordoma: incidence and survival patterns in the United States, 1973-1995.
AB  - BACKGROUND: Chordoma, a rare tumor arising from notochordal remnants, has been
      described to date only by single-institution case series or small population
      based surveys. METHODS: We used data from the Surveillance, Epidemiology, and End
      Results (SEER) program of the National Cancer Institute, 1973-1995, to calculate
      age-adjusted incidence and survival rates for 400 cases of microscopically
      confirmed chordoma and to derive information regarding case distribution and risk
      of second cancer. RESULTS: The age-adjusted chordoma incidence rate (IR) of 0.08
      per 100,000 was age-dependent, more common in males (IR 0.10) than females (IR
      0.06) and rare among patients aged <40 years and blacks. Within the axial
      skeleton 32% of cases were cranial, 32.8% spinal and 29.2% sacral. Young age (<26
      years; p = 0.0001) and female sex (p = 0.037) were associated with greater
      likelihood of cranial presentation. There was no overall increased risk for
      second primary cancers after chordoma. Median survival was 6.29 years; 5- and 10
      year relative survival rates were 67.6% and 39.9%, respectively. Comparison with
      other bone sarcomas revealed racial disparities in incidence for the two
      developmental tumors, chordoma and Ewing's sarcoma. CONCLUSIONS: This study
      provides new data regarding incidence and survival patterns of chordoma in the
      US. Additional epidemiologic studies are required to elucidate the genetic and
      environmental determinants underlying this rare, distinctive neoplasm.

PMID- 11227921
TI  - A prospective study of obesity and cancer risk (Sweden).
AB  - OBJECTIVE: [corrected] We evaluated the relation between obesity and the risks
      for various forms of cancer. METHODS: In a population-based cohort of 28,129
      hospital patients (8165 men, 19,964 women) with any discharge diagnosis of
      obesity (9557 only diagnosis, 5266 primary, 13,306 secondary) during 1965-1993,
      cancer incidence was ascertained through 1993 by record linkage to the nationwide
      Swedish Cancer Registry. Cancer risk was estimated using the standardized
      incidence ratio (SIR, with 95% confidence interval), which is the ratio of the
      observed number of cancers to that expected. RESULTS: Overall, a 33% excess
      incidence of cancer was seen in obese persons, 25% in men and 37% in women.
      Significant risk elevations were observed for cancers of the small intestine (SIR
      = 2.8; 95% CI 1.6-4.5), colon (1.3; 1.1-1.5), gallbladder (1.6; 1.1-2.3),
      pancreas (1.5; 1.1-1.9), larynx (2.1; 1.1-3.5), renal parenchyma (2.3; 1.8-2.8),
      bladder (1.2; 1.0-1.6), cervix uteri (1.4; 1.1-1.9), endometrium (2.9; 2.5-3.4),
      ovary (1.2; 1.1-1.5), brain (1.5; 1.2-1.9), and connective tissue (1.9; 1.1-3.0),
      and for lymphomas (1.4; 1.0-1.7), with higher risk observed for Hodgkin's disease
      only in men (3.3; 1.4-6.5) and for non-Hodgkin's lymphoma only in women (1.6; 1.2
      2.1). The association of obesity with risk of breast, prostate and pancreas
      cancers was modified by age. CONCLUSIONS: Obesity is associated with more forms
      of cancer than previously reported.

PMID- 11227922
TI  - Peanut butter intake, GSTM1 genotype and hepatocellular carcinoma: a case-control
      study in Sudan.
AB  - OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the major cancers in the
      world. In Sudan the incidence is thought to be high and increasing. This study
      aims to assess the association between peanut butter intake, as a source of
      aflatoxins, and the GSTM1 genotype in the etiology of HCC. METHOD: A case control
      study was conducted among 150 patients and 205 controls from two regions in
      Sudan. Food habits with special reference to peanut butter consumption, as well
      as peanut storage systems, have been investigated, as well as confounders such as
      hepatitis, drinking and smoking habits, and demographic characteristics. GSTM1
      genotype was assessed in DNA extracted from blood samples (110 cases, 189
      controls). RESULTS: A positive association was observed for highest vs. lowest
      quartile of peanut butter intake, humid storage system and HCC, with ORs (95% CI)
      being 3.0 (1.6-5.5) and 1.6 (1.1-2.5) respectively. The positive association with
      peanut butter intake was essentially limited to subjects with GSTM1 null genotype
      with OR for highest vs. lowest quartile 16.7 (2.7-105). CONCLUSION: Peanut butter
      consumption has been identified as a strong risk factor of HCC in a region with
      endemic aflatoxin contamination in Sudan and was essentially limited to subjects
      with the GSTM1 null genotype.

PMID- 11227923
TI  - Public awareness of warning signs for cancer in Britain.
AB  - BACKGROUND: The objective of this study was to establish the level of public
      awareness of warning signs for cancer in Britain. METHODS: An interview-based
      survey of a representative sample of the UK population was undertaken; 3693 men
      and women completed the interview (69% response rate). The data from this survey
      included demographic characteristics as well as recognition of the 'seven warning
      signs for cancer'. FINDINGS: Results revealed that recognition of signs ranged
      from 81% ('thickening or lump'; n = 2994) to 37% ('indigestion/difficulty
      swallowing'; n = 1356). On average participants identified 4.2 of the signs, with
      only 1.6% (n = 58) identifying all seven. There were strong associations with
      demographic characteristics, with better recognition being associated with being
      female, married, higher socioeconomic status (SES), higher income, a homeowner
      and having more years of education. INTERPRETATION: From these results we
      conclude that fewer than one in ten of the UK population can recognize seven
      warning signs for cancer, but the mean number recognized (4.2 signs) suggests
      that there is a reasonable level of public awareness. It must be cause for
      concern that most markers of lower SES are independently associated with poorer
      recognition, suggesting that public education needs to do more to narrow the
      inequalities in health knowledge.

PMID- 11227924
TI  - Mammography screening in Norway: results from the first screening round in four
      counties and cost-effectiveness of a modeled nationwide screening.
AB  - OBJECTIVE: To evaluate whether the results of the first screening round in the
      Norwegian Breast Cancer Screening Program predict future mortality reduction and
      to explore the cost-effectiveness of the program. METHODS: The results of
      surrogate measures were calculated and compared with the targets. A cost
      effectiveness analysis was performed assuming a nationwide program starting in
      1996 with an attendance rate of 80% and a mortality reduction of 30%. RESULTS:
      The attendance rate was 79.5% and the detection rate was 0.67%. The proportion of
      invasive tumors smaller than 15 mm was 53.1%, and 21.7% of the patients who
      underwent axillary surgery had lymphatic metastasis. The C/E ratios were found to
      be 3750 US dollars (USD) per year of life saved and 86,045 USD per life saved.
      CONCLUSION: The results of the first screening round will lead to a mortality
      reduction of at least 30%. The cost-effectiveness analysis shows that it is
      possible to run a highly cost-efficient screening program in Norway.

PMID- 11227925
TI  - Circulating levels of sex hormones and their relation to risk factors for breast
      cancer: a cross-sectional study in 1092 pre- and postmenopausal women (United
      Kingdom).
AB  - OBJECTIVE: To investigate the relationships between plasma concentrations of sex
      hormones and risk factors for breast cancer. METHODS: We investigated the
      relationship of plasma concentrations of estradiol, progesterone, follicle
      stimulating hormone (FSH), luteinizing hormone (LH) and sex hormone-binding
      globulin (SHBG) with breast cancer risk factors in 636 premenopausal and 456
      postmenopausal women. Risk factor data were obtained from questionnaires and
      hormone concentrations measured by immunoassays; variations in geometric means
      were compared using analysis of covariance. RESULTS: SHBG decreased with
      increasing body mass index and increasing waist-hip ratio both in pre- and
      postmenopausal women. In postmenopausal women only, estradiol increased with
      increasing body mass index. In premenopausal women, estradiol decreased with
      increasing physical activity, estradiol was higher in current than in ex- and non
      smokers, and FSH decreased with increasing alcohol intake. No associations were
      observed between sex hormones and age at menarche, parity, age at menopause, and
      previous use of oral contraceptives in either pre- or postmenopausal women.
      CONCLUSIONS: Certain factors such as obesity and perhaps waist-hip ratio,
      physical activity and alcohol consumption, but probably not age at menarche and
      parity, may mediate their effects on breast cancer risk by changing circulating
      concentrations of sex hormones.

PMID- 11227926
TI  - Race-specific results of Papanicolaou testing and the rate of cervical neoplasia
      in the National Breast and Cervical Cancer Early Detection Program, 1991-1998
      (United States).
AB  - OBJECTIVE: To describe differences in cervical screening and biopsy results by
      race or ethnicity from women in the National Breast and Cervical Cancer Early
      Detection Program (NBCCEDP). METHODS: We examined the percentage of abnormalities
      detected by Papanicolaou (Pap) tests and the rate of biopsy-diagnosed high-grade
      precancerous or cancerous lesions by racial or ethnic group. RESULTS: Almost half
      the 628,085 women screened were members of racial or ethnic minority groups.
      American Indian or Alaska Native women were more likely than others to report
      never having had a prior Pap test. American Indian or Alaska Native women had the
      highest proportion of abnormal Pap tests for first program screens (4.4%),
      followed by blacks (3.2%), whites (3.0%), Hispanics (2.7%), and Asians or Pacific
      Islanders (1.9%). Whites had the highest biopsy detection rate of high-grade
      lesions for first program screens (9.9 per 1000 Pap tests), followed by Hispanics
      (7.6), blacks (7.1), American Indians or Alaska Natives (6.7), and Asians or
      Pacific Islanders (5.4). CONCLUSIONS: This program provides important data on the
      prevalence of cervical neoplasia among diverse populations. Our findings that
      black women with a high-grade Pap test were less likely to get a work-up are
      disconcerting and merit further study and ultimate correction.

PMID- 11227927
TI  - Childhood sun exposure as a risk factor for melanoma: a systematic review of
      epidemiologic studies.
AB  - OBJECTIVE: To review the evidence that childhood is a period of particular
      susceptibility to the carcinogenic effects of solar radiation. METHODS: Studies
      were identified through searches of computerized bibliographic databases and
      article reference lists. Eligible studies were those that reported risks of
      melanoma associated with sun exposure during two or more age-periods. RESULTS:
      The measurement of childhood sun exposure varied across studies, preventing
      formal meta-analysis for most measures. We found that the way in which sun
      exposure was measured led to strikingly different conclusions regarding the
      association between age-specific sun exposure and risk of melanoma. Ecological
      studies assessing ambient sun exposure consistently reported lower risks of
      melanoma among people who resided in a low ultraviolet (UV) environment in
      childhood compared with those who resided in a high UV environment. In contrast,
      case-control studies differed widely in their findings, and no consistent
      associations with childhood sun exposure were observed. CONCLUSIONS: Ecological
      studies provided better-quality evidence than case-control studies for examining
      the effects of exposure to sunlight during specific age periods. Exposure to high
      levels of sunlight in childhood is a strong determinant of melanoma risk, but sun
      exposure in adulthood also plays a role.

PMID- 11227928
TI  - A population-based case-control study of carotenoid and vitamin A intake and
      ovarian cancer (United States).
AB  - OBJECTIVE: To evaluate the association between dietary intake of carotenoids and
      vitamin A and the incidence of ovarian cancer. METHODS: We conducted a population
      based case-control study of ovarian cancer in Massachusetts and Wisconsin.
      Incident cases diagnosed between 1991 and 1994 were identified through statewide
      tumor registries. We selected community controls at random from lists of licensed
      drivers and Medicare recipients; 327 cases and 3129 controls were included in the
      analysis. Data were collected by telephone interview, which included an
      abbreviated food and supplement list to quantify typical consumption of
      carotenoids (lutein/zeaxanthin, alpha-carotene, beta-carotene), retinol and total
      vitamin A at 5 years prior to diagnosis in cases, or to a comparable reference
      date in controls. Results were adjusted for age, state, and other risk factors.
      RESULTS: Participants with the highest dietary intake of lutein/zeaxanthin (> or
      =24,000 microg/week) experienced a 40% lower risk of ovarian cancer (95% CI =
      0.36-0.99) compared to those with the lowest intake. Intake of alpha-carotene,
      beta-carotene, retinol and total vitamin A was unrelated to risk. Among foods, we
      observed non-significantly lower risks with high consumption of spinach, carrots,
      skim/lowfat milk and liver. CONCLUSION: These results support previous findings
      suggesting an inverse relationship between carotenoid intake and ovarian cancer
      risk.

PMID- 11227929
TI  - Addressing class-based disparities related to tobacco: working with labor unions.

PMID- 11227930
TI  - Hyperplastic polyps of the colorectum-innocent or guilty?
AB  - Hyperplastic polyps have traditionally been regarded as nonneoplastic polyps
      lacking malignant potential. The demonstration of genetic alterations within
      these lesions indicates an underlying neoplastic cause. There is evidence that
      hyperplastic polyps are heterogeneous. Most are innocuous, but subsets may have
      malignant potential. Risk factors for neoplastic progression include multiple,
      large, and proximally located polyps. Aberrant methylation resulting in the
      silencing of cancer genes may be an important underlying mechanism, particularly
      in pathways progressing to tumors with DNA microsatellite instability. Lesions
      intermediate between hyperplastic polyp and cancer include admixed polyps and
      serrated adenomas. Currently, pathologists have different thresholds for
      diagnosing serrated adenomas, including the distinction from large hyperplastic
      polyps. Reasons for over looking this pathway in the past may include rapid tumor
      progression and the fact that proximally located hyperplastic polyps may be flat
      and not especially numerous. Management of the serrated pathway of colorectal
      neoplasia may require novel approaches to screening, early detection, and
      prevention.

PMID- 11227931
TI  - Evaluation of the sacroanal motor pathway by magnetic and electric stimulation in
      patients with fecal incontinence.
AB  - PURPOSE: The aim of this controlled study was to examine whether it was feasible
      to use magnetic stimulation as a new diagnostic tool to evaluate the motor
      function of the sacral roots and the pudendal nerves in patients with fecal
      incontinence. PATIENTS AND METHODS: Nineteen consecutive patients (17 females)
      with a median age of 67 (range, 36-78) years referred for fecal incontinence and
      14 healthy volunteers (six females) with a median age of 42 (range, 23-69) years
      were examined. Latency times of the motor response of the external anal sphincter
      were measured after electric transrectal stimulation of the pudendal nerve and
      magnetic stimulation of the sacral roots. RESULTS: The success rates of pudendal
      nerve terminal motor latency and sacral root terminal motor latency measurements
      were 100 and 85 percent, respectively, in the control group and 94 and 81
      percent, respectively, in the fecal incontinence group. Median left pudendal
      nerve terminal motor latency was 1.88 (range, 1.4-2.9) milliseconds in the
      control group and 2.3 (range, 1.8-4) milliseconds in the fecal incontinence group
      (P < 0.006). Median right pudendal nerve terminal motor latency was 1.7 (range,
      1.3-3.4) milliseconds in the control group and 2.5 (range, 1.7-6) milliseconds in
      the fecal incontinence group (P < 0.003). Median left sacral root terminal motor
      latency was 3.3 (range, 2.1-6) milliseconds in the control group and 3.7 (range,
      2.8-4.8) milliseconds in the fecal incontinence group (P < 0.03). Median right
      sacral root terminal motor latency was 3 (range, 2.6-5.8) milliseconds in the
      control group and 3.9 (range, 2.5-7.2) milliseconds in the fecal incontinence
      group (P = 0.15). CONCLUSIONS: Combined pudendal nerve terminal motor latency and
      sacral root terminal motor latency measurements may allow us to study both
      proximal and distal pudendal nerve motor function in patients with fecal
      incontinence. Values of sacral root terminal motor latency have to be interpreted
      cautiously because of the uncertainty about the exact site of magnetic
      stimulation and the limited magnetic field strength.

PMID- 11227932
TI  - Locally recurrent rectal cancer: predictors and success of salvage surgery.
AB  - PURPOSE: After curative surgery for rectal cancer, patients with pelvic
      recurrence may undergo curative surgical resection. We determined whether salvage
      surgery in appropriately selected patients could significantly lengthen disease
      free survival time and if so what factors predicted this outcome. METHOD: We
      reviewed the records of all patients treated for rectal cancer at our institution
      between 1980 and 1993. Of 937 patients who underwent surgery with curative intent
      after proctectomy or transanal local excision, 81 (8.6 percent) experienced local
      recurrence. During the same period 36 patients with locally recurrent rectal
      cancer were referred from other institutions. Logistic regression analysis was
      used to identify predictors of salvage surgery. The Kaplan-Meier method was used
      to estimate cancer-specific and disease-free survival times in 43 patients who
      underwent salvage surgery. The Cox proportional hazard model was used to identify
      factors associated with these outcomes. RESULTS: Of 117 patients with locally
      recurrent rectal cancer, 43 (36.7 percent) underwent salvage surgery. Factors
      associated with higher chance of receiving salvage surgery were female gender,
      the first operation performed at outside institutions, and transanal local
      excision as the initial operation. For 43 patients who underwent salvage surgery,
      five-year cancer-specific and disease-free survival rates were 49.7 and 32.2
      percent, respectively. No factors were significantly associated with death caused
      by cancer. However, a trend for poor prognosis was observed in patients with
      recurrence diameter >3 cm and tumor fixation Degree 2. CONCLUSION: Salvage
      surgery for properly selected patients with locally recurrent rectal cancer
      allows long-term palliation and significantly lengthens disease-free survival.

PMID- 11227933
TI  - Long-term follow-up of patients undergoing colectomy for colonic inertia.
AB  - PURPOSE: Total abdominal colectomy with ileorectal anastomosis has been the
      procedure of choice for patients with the established diagnosis of colonic
      inertia. Previous studies with a limited follow-up of only one to two years have
      shown acceptable results and a high rate of patient satisfaction. The aim of this
      study was to evaluate the long-term results of total abdominal colectomy in these
      patients in terms of complications, bowel function, and overall patient
      satisfaction. METHODS: Access to the colorectal registry at the Cleveland Clinic
      Florida identified all patients who underwent total abdominal colectomy for
      colonic inertia between 1988 and 1993, with a minimum of five-year follow-up.
      Telephone interviews were designed to assess bowel function, concomitant use of
      any antidiarrheal medications, postoperative complications, persistence or
      development of preoperative symptoms such as pain or bloating, and overall
      satisfaction. Patients were asked to rate their outcome as excellent, good, fair,
      or poor. RESULTS: Fifty patients underwent total abdominal colectomy for the
      diagnosis of colonic inertia. Three patients died of unrelated causes and 30 (60
      percent) were available for follow-up. The mean follow-up was 106 months, ranging
      from 61 to 122 months. All 30 patients reported the outcome of surgery as
      "excellent." The average frequency of spontaneous bowel movements was 2.5 (range,
      1-6) per day. During the period of follow-up, six patients (20 percent) required
      admission for small-bowel obstruction, three of whom (10 percent) required
      laparotomy. Four patients complained of mild pelvic pain, only one of whom had
      the onset of pelvic pain postoperatively that persisted until the time of
      interview. In the other three patients the pain was present preoperatively but
      had decreased in intensity since the operation. Two patients (6 percent) still
      required assistance with bowel movements, one by laxatives and the other by
      enemas. Only two patients (6 percent) needed antidiarrheal medications to reduce
      bowel frequency. CONCLUSION: This long-term follow-up revealed a high degree of
      patient satisfaction and very good bowel habits, with an acceptable long-term
      rate of bowel obstruction. Based on these results, total abdominal colectomy can
      be recommended to patients with well-established colonic inertia with
      expectations of sustained benefit up to ten years after surgery.

PMID- 11227934
TI  - Electrical impedance, a sensory system for detection of rectal filling after
      anorectal reconstruction: experimental study of rectal impedance measurements and
      defecation in dogs.
AB  - BACKGROUND: Total anorectal reconstruction with dynamic graciloplasty is an
      alternative to a permanent colostomy; however, perfect continence cannot be
      achieved because of loss of sensitivity. This study was designed in dogs to
      determine whether monitoring of rectal electric impedance can give information
      about fullness or motility of the rectum. METHODS: Four adult female beagle dogs
      underwent rectal electric impedance measurements using a bipolar electrode
      implanted on the rectal wall. An alternating current of 1 microA at a frequency
      of 4 kHz was applied between the two wires. Variations of impedance (called
      impedance waves), defecations, and weight of stools were recorded and analyzed.
      RESULTS: The basal rectal impedance was 682+/-19 omega. During the period of
      observation (n = 4), 84 impedance waves (amplitude, 72+/-2 omega; duration, 58+/
      11 minutes) were observed and 33 defecations (weight of stools, 74+/-6 g)
      occurred. Four types of impedance waves were identified and classified into two
      groups: low-amplitude or short-duration waves (Types I, II, and III), and high
      amplitude and long-duration waves (Type IV). Frequency of defecation was
      associated with the amplitude of the waves. The weight of stools was correlated
      with the duration of the waves (r = 0.574, n = 27, P = 0.002). Types I, II, and
      III waves were correlated with eventual partial defecations, whereas Type IV
      waves were correlated with complete defecations. After defecation, no spontaneous
      new defecation occurred before recovering at least 80 percent of the basal
      impedance. CONCLUSIONS: Rectal impedance variations are correlated with
      defecation in a canine model, and single bipolar measurements provide a suitable
      evaluation of rectum fullness. This suggests the possible use of impedance
      signals to control electrostimulated graciloplasty after anorectal
      reconstruction.

PMID- 11227935
TI  - Rectal augmentation and stimulated gracilis anal neosphincter: a new approach in
      the management of fecal urgency and incontinence.
AB  - PURPOSE: The aim of this study was the development of a procedure which would
      successfully treat selected patients presenting with incapacitating urgency and
      fecal incontinence. Some patients presenting with urgency and fecal incontinence,
      with an intact anorectum but deficient sphincter mechanism, have low rectal
      compliance. Management is problematic, because correction of the sphincter defect
      does not abolish the incapacitating urgency caused by rectal hypersensitivity.
      METHODS: This was a prospective study of three female patients with urgency and
      fecal incontinence who underwent combined rectal augmentation using a segment of
      distal ileum and stimulated gracilis anal neosphincter. All patients had low
      rectal volumes and two exhibited a temporal relationship between high-amplitude
      (>60 mmHg) rectal pressure waves and urgency on prolonged ambulatory anorectal
      manometry. RESULTS: Urgency was abolished and continence restored in all
      individuals. When the level of stimulation was not optimal or had been
      discontinued, patients experienced only passive incontinence with no urgency.
      Postoperative physiology revealed elevated thresholds to rectal distention and a
      reduction in the number of high-amplitude rectal pressure waves in all cases.
      CONCLUSIONS: Combined rectal augmentation with stimulated gracilis anal
      neosphincter may be of benefit to some patients with distressing urgency and
      fecal incontinence not previously helped by current techniques.

PMID- 11227936
TI  - Comparison of methods used for measurement of rectal compliance.
AB  - INTRODUCTION: Compliance is defined as the change in volume or cross-sectional
      area divided by the change in pressure. Pressure-volume measurement during
      distention with a compliant balloon is the most commonly used method for
      computation of rectal compliance. However, intraindividual and interindividual
      variations are large, restricting the usefulness of the method. Other methods
      such as rectal distention by a large, noncompliant bag and rectal impedance
      planimetry for assessment of pressure-cross-sectional-area relations have been
      proposed as alternatives owing to the reduction of errors from elongation of the
      balloon within the rectal lumen. However, in vivo reproducibility of pressure
      volume measurement during distention with a compliant balloon, pressure-volume
      measurement during rectal distention by a large, noncompliant bag, and rectal
      impedance planimetry have never been compared. PURPOSE: The aim of this study was
      to compare in vivo reproducibility of the above-mentioned methods and to study
      their in vitro reproducibility and validity. METHODS: Ten healthy volunteers (six
      men) aged 21-59 years were randomized to either rectal pressure-volume
      measurement with a compliant balloon or rectal impedance planimetry. After a one
      hour rest, the other procedure was performed. After two weeks, both procedures
      were again performed in the same order. During rectal impedance planimetry the
      volume of the bag used (maximum volume 450 ml; secured at both ends to the probe)
      was continuously registered, measuring pressure-volume relations during rectal
      distention by a large, noncompliant bag. Reproducibility was tested by comparing
      the difference divided by the mean for each method at eight pressure steps in the
      range from 5 to 40 cm H2O. Furthermore, the in vitro reproducibility and validity
      of the three methods were studied using polyvinyl chloride tubes with known cross
      sectional areas. RESULTS: In vivo reproducibility for pressure-volume measurement
      with a large, noncompliant bag and rectal impedance planimetry was significantly
      better than for pressure-volume measurement with a compliant balloon (P = 0.005
      and P = 0.019, respectively). No statistically significant difference was found
      between pressure-volume measurement with a large, noncompliant bag and rectal
      impedance planimetry (P = 0.20). In vitro reproducibility of pressure-volume
      measurement with a large, noncompliant bag and rectal impedance planimetry was
      good, but some elongation occurred, reducing the validity of pressure-volume
      measurement with a large, noncompliant bag. Coiling and elongation of the balloon
      within the lumen were major sources of error for pressure-volume measurement with
      a compliant balloon. CONCLUSION: In vivo and in vitro reproducibility of methods
      used for measurement of rectal compliance can be improved by restricting the
      effects of elongation within the lumen either by using a large-volume,
      noncompliant bag or by rectal impedance planimetry. However, pressure-volume
      measurement will to some degree depend on the properties of the balloons or bags.

PMID- 11227937
TI  - Importance of conversion for results obtained with laparoscopic colorectal
      surgery.
AB  - PURPOSE: The need for a conversion is a problem inherent in laparoscopic surgery.
      The present study points up the significance of conversion for the results
      obtained with laparoscopic colorectal surgery and identifies the risk factors
      that establish the need for conversion. METHOD: The study took the form of a
      multicentric, prospective, observational study within the Laparoscopic Colorectal
      Surgery Study Group. A total of 33 institutions in Germany, Austria, and
      Switzerland participated. The study period was 3.5 years. Cases were documented
      with the aid of a standardized questionnaire. RESULTS: Within the framework of
      the Laparoscopic Colorectal Surgery Study Group, a total of 1,658 patients were
      recruited to a multicenter study over a period of three and one-half years (from
      August 1, 1995 to February 1, 1999). The observed conversion rate was 5.2 percent
      (n = 86). The patients requiring a conversion were significantly heavier (body
      mass index, 26.5 vs. 24.9) than those undergoing pure laparoscopy. Resections of
      the rectum were associated with a higher risk for conversion (20.9 vs. 13
      percent). Intraoperative complications occurred significantly more frequently in
      the conversion group (27.9 vs. 3.8 percent). The duration of the operation was
      significantly increased after conversion in a considerable proportion of the
      procedures performed. Postoperative morbidity (47.7 vs. 26.1 percent), mortality
      (3.5 vs. 1.5 percent), recovery time, and postoperative hospital stay were all
      negatively influenced by conversion, in part significantly. Institutions with
      experience of more than 100 laparoscopic colorectal procedures proved to have a
      significantly lower conversion rate than those with experience of fewer than 100
      such interventions (4.3 vs. 6.9 percent). CONCLUSION: Although, of itself,
      conversion is not considered to be a complication of laparoscopic surgery, it is
      true that the postoperative course after conversion is associated with
      appreciably poorer results in terms of morbidity, mortality, convalescence, blood
      transfusion requirement, and postoperative hospital stay. The importance of
      experience in laparoscopic surgery can be demonstrated on the basis of the
      conversion rates. Careful patient selection oriented to the experience of the
      surgeon is required if we are to keep the conversion, morbidity, and mortality
      rates of laparoscopic colorectal procedures as low as possible.

PMID- 11227938
TI  - Defining a learning curve for laparoscopic colorectal resections.
AB  - PURPOSE: The purpose of this review was to define the learning curve for
      laparoscopic colorectal resections. METHODS: A prospectively accumulated,
      computerized database of all laparoscopic colorectal resections performed by
      three surgeons between April 1991 and March 1999 was reviewed. RESULTS: A total
      of 461 consecutive resections were evenly distributed among three surgeons (141,
      155, and 165). Median operating time was 180 minutes for Cases 1 to 30 in each
      surgeon's experience and declined to a steady state (150-167.5 minutes) for Cases
      31 and higher. Subsequently, Cases 1 to 30 were considered "early experience,"
      whereas Cases 31 and higher were combined as "late experience" for statistical
      analysis. There were no significant differences between patients undergoing
      resections in the early experience and those undergoing resections in the late
      experience with respect to age, weight, or proportion of patients with
      malignancy, diverticulitis, or inflammatory bowel disease. There were greater
      proportions of males (42 vs. 54 percent, P = 0.046) and rectal resections
      performed (14 vs. 32 percent, P = 0.002) in the late experience. Trends toward
      declining rates of intraoperative complications (9 vs. 7 percent, P = 0.70) and
      conversion to open surgery (13.5 vs. 9.7 percent, P = 0.39) were observed with
      experience. Median operating time (180 vs. 160 minutes, P < 0.001) and overall
      length of postoperative hospital stay (6.5 vs. 5 days, P < 0.001) declined
      significantly with experience. There was no difference in the rate of
      postoperative complications between early and late experience (30 vs. 32 percent,
      P = 0.827). CONCLUSIONS: The learning curve for performing colorectal resections
      was approximately 30 procedures in this study, based on a decline in operating
      time, intraoperative complications, and conversion rate. Learning was also
      extended to clinical care because it was appreciated that patients could be
      discharged to their homes more quickly.

PMID- 11227939
TI  - Comparative evaluation of surgical stress of laparoscopic and open surgeries for
      colorectal carcinoma.
AB  - PURPOSE: To objectively evaluate the benefits of laparoscopic procedures for
      colorectal carcinoma, a prospective study to measure the stress response to
      laparoscopic surgery (n = 15) compared with open surgery (n = 12) was undertaken.
      In addition, to compare the various parameters relevant to surgical stress, the
      major surgery group (transthoracic esophagectomy for esophageal carcinoma, n = 4;
      and left upper abdominal evisceration for gastric carcinoma, n = 3) was assigned.
      METHODS: Peripheral blood samples were obtained to measure serum interleukin-6, C
      reactive protein, peripheral leukocytes, and lymphocyte counts. Additionally, the
      level of lymphocyte apoptosis was quantified using flow cytometry. RESULTS: The
      interleukin-6 and C-reactive protein levels were significantly greater in the
      open group than in the laparoscopy group one day (P < 0.05) and two days (P <
      0.05) after surgery, respectively. In the laparoscopy group, lymphocyte counts
      were significantly higher than in the open group two days after surgery. The
      laparoscopy and open groups did not differ significantly in their lymphocyte
      apoptotic index. In the major surgery group, the apoptotic index was
      significantly higher than in either the laparoscopy group or the open group in
      the early postoperative period. CONCLUSION: Changes in the various parameters
      pertinent to surgical stress evaluated in this study suggest that laparoscopic
      surgery for colorectal carcinoma leads to less postoperative stress than
      conventional open surgery.

PMID- 11227940
TI  - High preoperative serum carcinoembryonic antigen predicts metastatic recurrence
      in potentially curative colonic cancer: results of a five-year study.
AB  - INTRODUCTION: Serum carcinoembryonic antigen is used mainly for tumor follow-up
      to detect recurrence of colonic cancer. However, raised preoperative
      carcinoembryonic antigen levels may be helpful for the identification of
      understaged cases and of patients meriting more intensive preoperative and
      postoperative diagnostic workup. METHODS: From a prospectively collected
      database, the data on 261 patients who had curative colonic carcinoma with a
      minimal follow-up of five years and who had preoperative carcinoembryonic antigen
      levels assessed were retrieved and analyzed. Outcome parameters were local and/or
      distant recurrence and time to recurrence. These parameters were correlated with
      Dukes staging and preoperative carcinoembryonic antigen levels. RESULTS: The
      cumulative disease-free survival of patients with a preoperative carcinoembryonic
      antigen level within the normal range was significantly better than that of those
      whose carcinoembryonic antigen was 5 ng/ml or more (P = 0.001). No patient with
      carcinoembryonic antigen levels less than 1 ng/ml developed metastatic
      recurrence. Twenty-three percent of all patients with a raised carcinoembryonic
      antigen above 5 ng/ml compared with 2.1 percent of patients with carcinoembryonic
      antigen below 5 ng/ml developed a metastasis at two years. At five years, these
      figures were 37.2 percent and 7.5 percent, respectively. Dukes staging and
      carcinoembryonic antigen levels were found to be directly correlated (P < 0.001)
      when all patients were included. Carcinoembryonic antigen of more of 15 ng/ml was
      found to be a significant adverse prognostic indicator for disease-free survival
      irrespective of Dukes staging (P < 0.02). Raised carcinoembryonic antigen levels
      predicted distant metastatic recurrence (P < 0.001) but did not predict local
      recurrence (P = 0.72). CONCLUSIONS: High preoperative carcinoembryonic antigen
      levels above 15 ng/ml predicted an increased risk of metastatic recurrence in
      potentially curative colonic cancer and may indicate undetectable disseminated
      disease. Preoperative carcinoembryonic antigen levels predict understaging and
      the possibility of distant recurrence. Such patients may therefore be selected
      for adjuvant therapy where indicated. Therefore, carcinoembryonic antigen is
      complementary to conventional Dukes staging for the prediction of recurrence and
      survival.

PMID- 11227941
TI  - Detection and typing of human papillomavirus in anal epidermoid carcinomas:
      sequence variation in the E7 gene of human papillomavirus Type 16.
AB  - INTRODUCTION: Human papillomavirus, particularly Type 16, plays a central role in
      the development of anogenital squamous-cell carcinomas. A common sequence
      variation of human papillomavirus Type 16 in cervical cancer cell lines and in
      cervical cancer tissues from Korean patients was recently reported. The present
      study was performed to determine the integration type of human papillomavirus DNA
      in anal epidermoid carcinoma and to identify the common sequence variations in
      the human papillomavirus Type 16 E7 gene that had been previously reported.
      METHODS: Twenty-one formalin-fixed, paraffin-embedded specimens collected from 29
      patients with anal epidermoid carcinomas treated at the Seoul National University
      Hospital over a ten-year period (1989-1998) were investigated. Genomic DNA from
      the 21 specimens was extracted and analyzed using the polymerase chain reaction
      with a general primer and a type-specific primer for human papillomavirus Types
      16 and 18. Direct sequencing was performed. As a control, 13 normal anal
      epithelia available from these patients were microdissected. As another control,
      21 hemorrhoidal squamous epithelia obtained from a demographically adjusted group
      were also analyzed. RESULTS: Human papillomavirus Type 16 DNA was present in all
      21 anal epidermoid carcinomas. All controls were negative for human
      papillomavirus DNA. Sequence analysis revealed that 57 percent (12/21) specimens
      showed two types of sequence variation in the E7 gene. One variant with a single
      nucleotide change at position 647 (amino acid 29, AAT-->AGT, asparagine to
      serine) was found in 38 percent (8/21) of the samples. This variant has been
      detected in cervical cancers from Korean patients: 19 (39 percent) of 49 cervical
      cancer tissues and 6 (50 percent) of 12 cervical cancer cell lines. Another
      single nucleotide change at position 645 (amino acid 28, TTA-->TTC, leucine to
      phenylalanine) was found in 19 percent (4/21) of the samples. These two variants
      exhibit a change of amino acid affecting the critical sites for Rb binding.
      CONCLUSION: Human papillomavirus Type 16 was found to be present in all 21 anal
      epidermoid carcinomas. Furthermore, in the Korean population, the most common
      sequence variant found in cervical

PMID- 11227942
TI  - Obstructing colonic cancer: failure and survival patterns over a ten-year follow
      up after one-stage curative surgery.
AB  - BACKGROUND: Large-bowel cancers that present as obstructing lesions have a poor
      prognosis. However, little is known of the reasons for the dismal survival and of
      failure patterns after potentially curative treatment. METHOD: An observational
      study and multivariate analysis were conducted to identify determinants of
      survival and to compare recurrence patterns between obstructing and
      nonobstructing tumors after primary resection and anastomosis as curative
      treatment. RESULTS: Over a period of ten years (1980-1989), 528 patients with
      colonic cancer were treated at one institution. The cancer was obstructing in 179
      cases and nonobstructing in 349. One-stage primary resection and anastomosis as
      curative treatment were performed in 107 obstructed and 256 nonobstructed
      patients. Three hundred thirty-six potentially cured survivors (94 in the former
      group and 242 in the latter) were followed for a median of 55 months. During
      follow-up, local recurrence occurred in 37 patients (12 obstructed (12.8 percent)
      and 25 nonobstructed (10.4 percent), P = 0.44) and metastatic disease in 68 (25
      obstructed (27.6 percent) and 43 nonobstructed (17.8 percent), P = 0.029).
      Multivariate analysis of survival showed that age over 70 years, Dukes stage,
      histologic grade, and recurrence were the only prognostic factors. No
      statistically significant determinant turned out for local recurrence, whereas at
      multivariate analysis for metastatic and overall relapse, Dukes stage, positive
      nodes, and obstruction remained independent prognostic factors. CONCLUSIONS:
      After one-stage emergency curative treatment, patients presenting with
      obstructing tumors of the colon have a smaller survival probability than that of
      patients with nonobstructing lesions. Local recurrence pattern is similar between
      groups. Conversely, obstruction, along with pathologic stage and positive nodes,
      carries a significantly higher risk of metastatic tumor recurrence and death.

PMID- 11227943
TI  - Predictors of proximal vs. distal colorectal cancers.
AB  - BACKGROUND: Because proximal colorectal cancers have a tendency to present at a
      more advanced stage and thus have a poorer prognosis, it is important to
      understand the factors associated with the development of proximal colorectal
      cancer. We hypothesized that older age, female gender, and the presence of
      comorbid illness would be associated with proximal cancers. METHODS: Incident
      cases of colorectal cancer (n = 9,550) occurring in 1994 were identified from
      Florida's population-based statewide cancer registry. We categorized colorectal
      cancers as either proximal (cecum, ascending colon, and transverse colon) or
      distal (descending colon, sigmoid colon, rectosigmoid, and rectum). Multiple
      logistic regression analysis was used to determine the multivariable relationship
      between clinical characteristics and the odds of a proximal-occurring lesion.
      RESULTS: Four characteristics emerged as independent predictors of a proximal
      lesion. Each year of increasing age was associated with a 2.2 percent increase in
      the odds of a proximal lesion, whereas female gender was associated with a 38
      percent increase in the odds of a proximal lesion. The presence of a comorbid
      condition was associated with a 28 percent greater odds of a proximal lesion,
      and, finally, black, non-Hispanic race was associated with a 24 percent greater
      odds of a proximal lesion. CONCLUSIONS: We found that increasing age, female
      gender, black, non-Hispanic race, and the presence of comorbid illnesses were
      factors associated with a greater likelihood of developing colorectal cancer in a
      proximal location. Further studies will be required to confirm these findings and
      to establish the mechanism by which comorbidity influences the site of colorectal
      cancer development.

PMID- 11227944
TI  - Identification of the fascia propria by magnetic resonance imaging and its
      relevance to preoperative assessment of rectal cancer.
AB  - If rectal cancer does not penetrate the fascia propria of the rectum and the
      rectum is removed with the fascial envelope intact (extrafascial excision), then
      local recurrence of the cancer will be minimal. Modern imaging techniques have
      identified a fascial plane surrounding the rectum and mesorectum, and it has been
      suggested that this is the fascia propria. The aim of this study was to identify
      whether this plane is the rectal fascia propria and whether tumor invasion
      through this fascia can be identified preoperatively. METHODS: Two separate
      experiments were performed: 1) pelvic magnetic resonance imaging was performed
      before and after dissection and marking of the plane of extrafascial dissection
      of the rectum of a cadaver; and 2) magnetic resonance imaging was performed in 43
      rectal cancer patients preoperatively. Two radiologists independently reported
      the depth of tumor invasion in relation to the fascia propria. The tumors were
      resected by extrafascial excision, and a pathologist independently reported the
      relation of the tumor to the fascia propria. RESULTS: The marker inserted in the
      extrafascial plane showed that the plane visualized on pelvic magnetic resonance
      imaging was the fascia propria dissected in extrafascial excision of the rectum.
      The magnetic resonance imaging detected tumor penetration through the fascia
      propria with a sensitivity of 67 percent, a specificity of 100 percent, and an
      accuracy of 95 percent. CONCLUSION: The surgical fascia propria can be identified
      on preoperative magnetic resonance imaging in patients with rectal cancer. Tumor
      invasion through this fascia can be detected on magnetic resonance imaging. This
      method of assessment offers a new way to select those patients who require
      preoperative radiotherapy.

PMID- 11227945
TI  - Surgical treatment of parastomal hernia complicating sigmoid colostomies.
AB  - PURPOSE: Parastomal hernia is a common late complication of colostomy. Surgical
      approach to the repair of parastomal hernia is controversial. Results of surgical
      treatment are disappointing. The aim of this study was to assess the outcome of
      surgical treatment of parastomal hernia. METHOD: This article reports a
      retrospective review of those patients who had undergone a surgical treatment of
      parastomal hernia complicating sigmoid colostomy. The indications, surgical
      procedures, complications, and outcome were carefully studied. RESULTS: There
      were 43 surgical treatments of parastomal hernia. Sixteen underwent simple local
      repair; 25 stomas were relocated, and 2 were locally repaired with mesh. Overall
      recurrence was 18 of 40 (45 percent). Recurrences for fascial repair and stoma
      relocation were 6 of 13 (46 percent) and 10 of 25 (40 percent), respectively.
      Stoma relocation could be accomplished without formal laparotomy in 19 of 25
      cases. Incisional hernia occurred in only 2 of these 25 relocations. CONCLUSION:
      Fascial repair alone can be performed for symptomatic small hernias because of
      its advantage of minimal morbidity. Stoma relocation without formal laparotomy
      can be advocated for larger hernias. A combination of local resite together with
      mesh reinforcement may be the alternative for further improvement of results.

PMID- 11227946
TI  - Genetic counseling and interpretation of genetic tests in familial adenomatous
      polyposis and hereditary nonpolyposis colorectal cancer.
AB  - PURPOSE: Genetic counseling and interpreting genetic test results can be complex.
      Moreover, without knowing the limitations of the methods used and the lifetime
      probability of developing cancer in individuals who carry a gene that predisposes
      to cancer, misinterpretation may lead to false assurance. The purpose of this
      review is to discuss how genetic counseling will benefit patients and their
      family, the genetic tests available for hereditary colorectal cancer syndromes,
      and the interpretation of results. METHODS: Current literature was reviewed and
      our clinical and research experiences were incorporated. RESULTS: This review
      serves as a guide to enable various health care providers to better counsel
      patients in their quest for advice on prevention, early detection, and
      surveillance for colorectal cancer. Notable topics of discussion are who should
      undergo genetic counseling and consider testing and how the interpretation of
      test results can be misleading; for example, understanding the difference between
      a no mutation detected vs. a negative test result. CONCLUSIONS: Genetic
      counseling is of paramount importance for patients to fully understand the
      limitations of genetic testing and will aid in the management of patients who are
      susceptible to colorectal cancer.

PMID- 11227947
TI  - On the technique of colostomy. 1888.

PMID- 11227948
TI  - Adenocarcinoma at a strictureplasty site in Crohn's disease: report of a case.
AB  - Strictureplasties have proven useful and safe in Crohn's disease. Concerns have
      been raised, however, about the potential of carcinoma arising at the
      strictureplasty site. Here the authors report a case of a small-bowel
      adenocarcinoma developing at the site of a prior strictureplasty in a middle-aged
      male patient seven years postoperatively in the absence of any other
      preneoplastic disease of the small bowel. Presenting symptoms were of progressive
      obstruction after a long period of quiescent disease. With this report comes
      stronger evidence that adenocarcinoma does occur at strictureplasty sites,
      raising questions of its long-term safety.

PMID- 11227949
TI  - Solitary pancreatic metastasis from a primary colonic tumor detected by PET scan:
      report of a case.
AB  - PURPOSE: A case of a solitary pancreatic metastasis from a primary colonic
      carcinoma is reported. METHODS: The history and use of carcinoembryonic antigen,
      computed tomography, and positron emission tomography in this case and the follow
      up of colorectal cancer are reviewed. RESULTS: Recurrent disease was suspected by
      an increasing carcinoembryonic antigen level. However, conventional imaging with
      computed tomography on more than one occasion failed to identify any recurrence.
      The pancreatic metastasis was accurately localized by positron emission
      tomography scanning and confirmed on subsequent laparotomy. A histologically
      complete resection was performed and the patient remained in remission with a
      normal carcinoembryonic antigen 12 months postoperatively. CONCLUSION: This case
      reports an unusual site of solitary metastasis in colorectal cancer and supports
      the further investigation of positron emission tomography in follow-up of
      colorectal cancer.

PMID- 11227950
TI  - Thoracic empyema associated with recurrent colon cancer: report of a case and
      review of the literature.
AB  - Many types of infections associated with colorectal cancer have been reported.
      Here, we describe a rare case of thoracic empyema that was observed during
      immunotherapy for recurrent colon cancer. Culture of the pleural fluid yielded
      Streptococcus bovis, which is known to be associated with gastrointestinal
      lesions, especially colorectal malignancies. The possible correlation between
      these two clinical entities-empyema and colon cancer-is discussed.

PMID- 11227952
TI  - How prevalent are alterations in bowel habits during menses?

PMID- 11227951
TI  - Gene expression analysis in colorectal cancer using practical DNA array filter.
AB  - PURPOSE: We examined the usability of a newly developed, compact-sized DNA array
      filter for studying the gene expression pattern of individual colorectal cancer.
      METHODS: Complementary DNA probes were prepared from mRNA extracted from colonic
      cancer specimens and adjacent normal mucosa and then were labeled with
      chemiluminescence. These labeled probes were allowed to bind to the gene
      fragments on the filter. A specialized scanning charge-coupled device camera
      measured the intensity of each chemiluminescent spot, which is an indicator of
      the degree to which a specific gene is expressed. Gene expression image was
      quantified into intensity of signals by using computer software. RESULTS:
      Characteristic gene expression patterns were obtained from the colonic cancer
      cell line, RPMI4788, and the leukemia cell line, HL60, by using this compact
      sized DNA array filter in the preliminary experiment. Up-regulation of nm23,
      TIMP1, VEGF, and cyclin E and down-regulation of some tumor suppressor genes
      (p53, TOSO, and SIVA), beta-catenin, and metallothionein were observed in colonic
      cancer specimen when compared with those of normal mucosa. CONCLUSIONS: We have
      obtained unique gene expression patterns from colorectal cancer and normal tissue
      by using a newly developed compact-sized DNA array filter system. Collecting,
      storing, and analyzing of gene expression data from many samples of colorectal
      cancer will enable us to identify distinct subsets of patients based on molecular
      characteristics in the near future.

PMID- 11227953
TI  - Do electrophysiological interventions confer a prothrombotic state?

PMID- 11227954
TI  - Atrial tachycardia or atrioventricular nodal reentry? An unusual case of a long
      RP tachycardia.

PMID- 11227955
TI  - Brugada syndrome: a case report of monomorphic ventricular tachycardia.
AB  - A 56-year-old woman without structural heart disease had an ECG typical of
      Brugada syndrome. Syncope occurred due to monomorphic VT with left bundle branch
      block (LBBB) morphology. At electrophysiological study, VT with the same
      morphology was inducible.

PMID- 11227956
TI  - Recurrent pericardial chest pain: a case of late right ventricular perforation
      after implantation of a transvenous active-fixation ICD lead.
AB  - A 36-year-old woman with a history of recurrent syncopal episodes presumably due
      to ventricular tachyarrhythmia in mitral valve prolapse underwent implantation of
      a transvenous ICD system. During a 23-month follow-up, she developed recurrent
      pericardial chest pain with pericardial friction rub. The first episode of chest
      pain occurred without any detectable change in pacing or sensing parameters. The
      second episode was associated with an increase in pacing threshold and drop in
      intracardiac signal amplitude. Right ventricular perforation was suspected
      fluoroscopically and confirmed by right ventriculography. This case report
      emphasizes the key steps in the diagnosis of this rare complication of an ICD
      implantation.

PMID- 11227957
TI  - Torsades de pointes ventricular tachycardia induced by mosapride and flecainide
      in the presence of hypokalemia.
AB  - We report a 68-year-old man who developed torsades de pointes ventricular
      tachycardia induced by combined use of mosapride and flecainide. He had a
      permanent pacemaker (DDD mode) implanted because of sick sinus syndrome
      (bradytachy syndrome) 6 years earlier. The patient had started taking mosapride
      for upper abdominal discomfort 2 weeks earlier. On admission, ECG showed
      prolongation of the QTc interval from 0.48 to 0.56 seconds and self-terminating
      torsades de pointes occurred. We considered that this proarrhythmia was induced
      by mosapride in combination with antiarrhythmic agents.

PMID- 11227958
TI  - Psychological treatment of malignant vasovagal syncope due to bloodphobia.
AB  - A 17-year-old boy with frequent faints due to blood-injury phobia was studied.
      During cardiovascular reflex investigation in our syncope unit, 50 seconds of
      asystole were recorded. He was treated using systematic desensitization with
      muscular tension and cognitive techniques by the Pediatric Psychosocial
      Department and has not experienced syncopal events again.

PMID- 11227959
TI  - Long-term follow-up of left ventricular pacing via a posterior cardiac vein after
      mechanical tricuspid valve replacement.
AB  - Permanent cardiac pacing was recommended in a 66-year-old woman with mechanical
      prosthetic mitral and tricuspid valves. To avoid a thoracotomy, a conventional
      endocardial lead was inserted with a steerable stylet (Locator) into the
      posterior cardiac vein via the right cephalic vein. Four weeks later, lead
      dislodgement required reoperation. The lead position remained stable up to 29
      months.

PMID- 11227960
TI  - Intermittent output failure of a VVI device due to the disintegration of the
      generator.
AB  - The metal case and the header of a Biovallees Coralite 247 pacemaker fell apart
      in a patient resulting in syncope due to myopotential inhibition. Upon recalling
      our patients with that type of device, we found a similar technological failure
      in 11 of 16 of them. This finding warrants a consideration for recalling that
      Biovallees device.

PMID- 11227961
TI  - Highest number of ICD implantations per million inhabitants from 1993-1998 in
      Austria.

PMID- 11227962
TI  - Inability to communicate with ICDs: an underreported failure mode.
AB  - The inability to perform telemetry on an ICD may have many potential causes. We
      report three recently identified cases where such a finding was indicative of
      unexpected device failure. Two of these cases involved identical failure
      mechanisms resulting from arcing of current within the high voltage hybrid. This
      placed the device into a high current state that caused rapid and complete
      battery depletion. There were no company alerts issued regarding this systematic
      problem. A multicenter arrhythmia device/lead database would be extremely useful
      in providing timely and unbiased information concerning device problems.

PMID- 11227963
TI  - Effects of sex and age on electrocardiographic and cardiac electrophysiological
      properties in adults.
AB  - Although differences in patient sex in heart rate and QT interval have been well
      characterized, sexual differences in other cardiac electrophysiological
      properties have not been well defined. The study population consisted of 354
      consecutive patients without structural heart disease or preexcitation who
      underwent clinically indicated electrophysiological testing in the drug-free
      state. Atrial, AV nodal, and ventricular effective refractory periods (AERP,
      AVNERP, VERP) were determined at a pacing cycle length of 500 ms using an 8-beat
      drive train and 3-second intertrain pause. There were 124 men and 230 women with
      a mean age of 45 +/- 19 and 47 +/- 18 years, respectively. The sinus cycle length
      (SCL) was longer in men than in women (864 +/- 186 and 824 +/- 172 ms,
      respectively, P < 0.05). The QRS duration was significantly longer in men (90 +/-
      12 ms) than women (86 +/- 13 ms) (P < 0.005). The HV interval was 48 +/- 9 ms in
      men and 45 +/- 8 ms in women (P < 0.05). The sinus node recovery time (SNRT) was
      significantly longer in men than in women (1215 +/- 297 ms and 1135 +/- 214 ms,
      respectively, P < 0.05). AERP and VERP were similar in both sexes. Aging did not
      influence sexual differences in cardiac electrophysiological properties,
      although, it independently prolonged the SCL, PR, and QT intervals, AH and HV
      intervals, SNRT, AVNERP, and the AV Wenckebach cycle length. The SCL, QRS
      duration, HV interval, and SNRT were significantly longer in men than in women.
      Aging prolonged cardiac conduction and increased the SCL but the effects were
      similar in both sexes. AERP and VERP were unaffected by aging or sex.

PMID- 11227964
TI  - A simple method of mapping atrial premature depolarizations triggering atrial
      fibrillation.
AB  - Atrial premature depolarizations (APDs) originating from focal sites,
      particularly the pulmonary veins (PV), may become triggers of atrial fibrillation
      (AF). Accurate mapping of APDs with conventional methods may be time consuming
      and expose the patient to unnecessary instrumentation of the left atrium. We
      hypothesized that the atrial activation sequence recorded using a simple system
      that includes an esophageal catheter and a custom-made 16-electrode catheter with
      two sets of floating electrodes eight in the coronary sinus and eight in the high
      right atrium) could be sufficient to localize the APDs. The study included 29
      patients with frequent APDs and AF refractory to antiarrhythmic medications. The
      APD site of origin was confirmed with single-point sequential mapping techniques
      using the CARTO system ten patients) or by placement of multielectrode catheters
      in the right and left PV (19 patients). Of the 29 patients, 20 patients had a
      single APD focus; 8 patients had two different APD morphologies; and 1 patient
      had three APD foci. Mapping for ablation of the APD foci showed earliest
      activation in the left superior PV in 12 patients, right superior PV in 15
      patients, right middle PV in 4 patients, right inferior PV in 1 patient, the
      lingular branch of the left superior PV in 2 patients, left inferior PV in 2
      patients, and right atrium along the crista terminalis in 3 patients. The
      activation sequence and relative timing of the recordings obtained with our
      catheter configuration was highly predictive of right and left atrial origin and,
      more importantly, of right and left PV foci.

PMID- 11227965
TI  - Septal lead implantation for the reduction of paced QRS duration using passive
      fixation leads.
AB  - In 120 consecutive patients with standard pacing indications, we tested the
      feasibility of RV septal lead implantation technique guided by surface ECG and
      the degree to which this technique reduces paced QRS duration compared to RV
      apical stimulation when passive-fixation leads are used. During implantation, an
      ECG was recorded with a paper speed of 100 mm/s using the orthogonal Frank leads,
      and QRS was measured from the earliest to the latest deflection in any of the
      Frank leads. Pace-mapping of the septum was performed until QRS was minimal. The
      lead was attached, where QRS, pacing threshold, lead impedance, and EGM amplitude
      provided the best compromise. An average of 3.7 +/- 2.5 attempts (range 1-18,
      median 7) was needed until a final implantation site was found. There were no
      technical problems during implantation. QRS could be reduced by 5-55 ms (mean
      delta QRS 19 +/- 11 ms) in 83 (69%) of 120 patients. In 22 (18%) patients, QRS
      was identical with apical and septal pacing, and in 15 (13%) patients, QRS was 5
      20 ms (10 +/- 4) longer despite septal stimulation. Average QRS was significantly
      shorter during septal pacing compared with apical pacing (151 +/- 20 vs 162 +/-
      23 ms, P < 0.001). There was a tendency towards greatest QRS reduction when the
      high septum was stimulated (22 +/- 11 ms reduction) as compared with mid- (18 +/-
      11 ms) or apical parts of the RV septum (16 +/- 10 ms). QRS reduction was most
      likely if apical QRS width was > 170 ms (P = 0.0002), and there was an inverse
      correlation between apical QRS and delta QRS (r = 0.53, P < 10(-7)). During a
      mean follow-up of 14 months, there was no pacing or sensing problem and no lead
      dislodgment occurred.

PMID- 11227966
TI  - Functional similarity between electrograms recorded from an implantable
      cardioverter defibrillator emulator and the surface electrocardiogram.
AB  - Clinical use of stored electrogram (EGM) configurations currently used in ICDs is
      limited. The hypothesis that EGMs recorded from electrodes on the ICD surface may
      improve diagnostic capabilities of the device was tested in the present study.
      The Buttons on Active Can Emulator (BACE), an ICD-sized device containing four
      button electrodes, was temporarily placed into a subcutaneous or submuscular left
      pectoral pocket in 16 patients during ICD implantation. Simultaneous recordings
      were obtained from the ECG lead II, bipolar EGMs using BACE electrodes, and a
      bipolar atrial EGM during sinus rhythm (SR), ventricular pacing (VP) at cycle
      lengths of 500 and 400 ms, and VT. Visible P waves were present in all patients
      during SR (n = 15), in 5 (33%) of 15 patients during VP, and none of the patients
      during VT (n = 4) using BACE EGMs and lead II. P and QRS amplitudes and the P:QRS
      ratio during SR in BACE EGMs were significantly lower than those in lead II. BACE
      EGMs showed prominent changes in QRS morphology and duration during VP and VT
      compared to SR, and the magnitude of QRS prolongation during VP was similar to
      that in lead II. Measurements of PR, QRS, and QT duration during SR showed good
      agreement between BACE EGMs and lead II. In conclusion, EGMs recorded from
      electrodes embedded on the ICD housing may potentially improve visual
      discrimination between supraventricular and ventricular arrhythmias. They also
      may be useful as a surrogate of the ECG for analysis and monitoring of different
      components of P-QRS-T complex.

PMID- 11227967
TI  - Paroxysmal tachycardia in children and teenagers with normal sinus rhythm and
      without heart disease.
AB  - The purpose of this study was to evaluate the value of esophageal programmed
      stimulation in children and teenagers with normal sinus rhythm ECG and normal
      noninvasive studies, having palpitations and syncope, and no documented
      tachycardias. Paroxysmal tachycardias are frequent in children and are often
      related to accessory connection. These tachycardias are sometimes difficult to
      prove. Transesophageal atrial pacing was performed at rest and during infusion of
      isoproterenol in 31 children or adolescents aged 9-19 years (16 +/- 3 years) with
      normal sinus rhythm ECG and suspected or documented episodes of paroxysmal
      tachycardia. Sustained tachycardia was induced in 27 patients, at rest in 13
      patients, and after isoproterenol in 14 remaining patients. Atrioventricular
      nodal reentrant tachycardia was found as the main cause of paroxysmal tachycardia
      (22 cases). Six patients were followed by a vagal reaction and dizziness. These
      patients had spontaneous tachycardia with syncope. In three other patients,
      atrial fibrillation was also induced. Concealed accessory pathway reentrant
      tachycardia was identified in three patients. In two patients, a regular wide
      tachycardia with right bundle branch block morphology was induced; the diagnosis
      of verapamil-sensitive ventricular tachycardia was made in a second study by
      intracardiac study. In conclusion, atrioventricular nodal reentrant tachycardia
      was found as the main cause of symptoms in children with normal sinus rhythm ECG.
      Syncope is frequently associated and provoked by a vagal reaction. This diagnosis
      could be underestimated in adolescents frequently considered as hysterical
      because noninvasive studies are negative.

PMID- 11227968
TI  - Mechanism of spontaneous transition from typical atrial flutter to atrial
      fibrillation: role of ectopic atrial fibrillation foci.
AB  - Paroxysmal AF has been known to be initiated by ectopic beats, especially in the
      pulmonary veins (PVs), and radiofrequency catheter ablation could cure it. We
      considered that the spontaneous transition from typical atrial flutter to AF also
      could be initiated by ectopic beats. Twenty patients (18 men, mean age 66 +/- 14
      years) with episodes of spontaneous transition from typical atrial flutter to AF
      were included in this study. They underwent detailed mapping of both atria. All
      the patients had spontaneous AF initiated by ectopic beats, and all of them had
      typical atrial flutter and spontaneous transition from typical atrial flutter (12
      patients with counterclockwise atrial flutter and 8 patients with clockwise
      atrial flutter) to AF. The transition was initiated by ectopic beats from the PVs
      (17 foci, 85%), crista terminalis (2 foci, 10%), and superior vena cava (1 focus,
      5%). After successful ablation of AF foci, typical atrial flutter was induced
      again, but no spontaneous transition was found after at least 10 minutes of
      observation. We concluded that paroxysmal AF and spontaneous transition from
      typical atrial flutter to AF were initiated by ectopic beats, and successful
      catheter ablation of the ectopic foci can eliminate paroxysmal AF and spontaneous
      transition from typical atrial flutter to AF.

PMID- 11227969
TI  - When should heparin preferably be administered during radiofrequency catheter
      ablation?
AB  - RF catheter ablation is complicated by thromboembolism in about 1% of patients.
      Limited knowledge exists concerning when and how to use anticoagulation or
      antithrombotic treatment. We studied the activation of coagulation (prothrombin
      fragment 1 + 2 [PF1 + 2] and D-dimer), platelets (beta-thromboglobulin [beta-TG])
      and fibrinolysis (plasmin-antiplasmin complexes [PAP]) during RF ablation of
      accessory pathways in 30 patients. They were randomized to receive heparin (100
      IU/kg, intravenously) (1) immediately after introduction of the femoral venous
      sheaths (group I) or (2) after the initial electrophysiological study, prior to
      the delivery of RF current (groups II and III). Group II additionally received
      saline irrigation of all femoral sheaths. After the initial bolus, 1,000 IU of
      heparin was supplied hourly in all groups. Within groups II and III, median
      plasma values of PF1 + 2 and beta-TG more than tripled (P < or = 0.007) during
      the diagnostic study and gradually declined during heparin administration despite
      RF current delivery. Median D-dimer tripled (P = 0.005) and PAP doubled (NS)
      before heparin administration; then both remained around the upper reference
      values. In the early heparin group, however, PF1 + 2, D-dimer, and PAP did not
      rise at all, and beta-TG showed only a slight increase towards the end of the
      procedure. The differences between group I versus groups II and III were
      statistically significant prior to the first RF current delivery (PF1 + 2, D
      dimer, and beta-TG) and by the end of the procedure (PF1 + 2, D-dimer, and PAP).
      In conclusion, "late" heparin administration allows hemostatic activation during
      the initial catheterization and diagnostic study. By administering intravenous
      heparin immediately after introduction of the venous sheaths, hemostatic
      activation is significantly decreased. Saline irrigation of the venous sheaths
      added nothing to late heparin administration.

PMID- 11227970
TI  - Effect of diabetes mellitus on heart rate variability in patients with congestive
      heart failure.
AB  - This study sought to determine if the severity of autonomic perturbations in
      patients with heart failure are affected by the presence of diabetes. Decreased
      HRV is frequent in diabetic patients free of clinically apparent heart disease
      and has been invoked as a risk factor for sudden cardiac death. However, reduced
      HRV is also commonly present in patients with left ventricular dysfunction. The
      effect of diabetes on autonomic dysfunction in this setting is not known. Holter
      ECGs from 69 diabetic patients and 85 nondiabetic control subjects with heart
      failure were analyzed. The severity of autonomic dysfunction was assessed using
      24-hour time- and frequency-domain HRV analysis. Prognostically important time-
      and frequency-domain HRV measures (SDNN, SDANN5, total power, and ultra-low
      frequency power) were not different between the two groups. Time- and frequency
      domain parameters modulated by parasympathetic tone (pNN50, RMSSD, and HF power)
      were depressed to a similar degree in the diabetic and the nondiabetic groups.
      The low frequency power was significantly lower in diabetic patients (5.8 +/- 0.7
      vs 5.3 +/- 1.0, P = 0.02). The ratio of low to high frequency power was
      substantially lower in the diabetic group (2.2 +/- 0.2 vs 1.4 +/- 0.2, P <
      0.0001). These differences were more apparent in insulin-treated diabetics. In
      the presence of heart failure, HRV parameters that are most predictive of adverse
      outcome are similar in diabetic and nondiabetic patients. Furthermore, during
      increased sympathetic stimulation in the setting of heart failure, diabetes does
      not worsen parasympathetic withdrawal but may mitigate sympathetic activation.

PMID- 11227972
TI  - Catheter ablation in the elderly in the United States: use in the Medicare
      population from 1991 to 1998.
AB  - The safety and efficacy of catheter ablation for the treatment of drug refractory
      cardiac arrhythmias is well established in young patients. Little is known about
      its effectiveness or use in the elderly. We determined trends in the use of
      catheter ablation in the United States Medicare population. Data were obtained
      from the approximately 30 million patients covered each year by Medicare's fee
      for-service program of the Health Care Financing Administration of the Department
      of Health and Human Services. From 1991 to 1998, Medicare's fee-for-service
      beneficiaries covered 80%-93% of all adults > 65 years old in the United States.
      All catheter-based ablative procedures performed in this population were
      identified through the use of the Current Procedural Terminology codes 93650,
      93651, and 93652. Use rate per 1 million beneficiaries grew from 33 in 1991 to
      603 in 1998. While during this 7-year period the Medicare fee-for-service
      population decreased by 8%, ablations increased 16-fold (1,608%). The use of
      catheter ablation in the older American grew exponentially during the 1990s.
      Further research is needed to determine the optimal use of this potentially
      curative technique in the elderly.

PMID- 11227971
TI  - Prospective randomized comparison of 50%/50% versus 65%/65% tilt biphasic
      waveform on defibrillation in humans.
AB  - It is unknown if there is a single optimal biphasic waveform for defibrillation.
      Biphasic waveform tilt may be an important determinant of defibrillation
      efficacy. The purpose of this study was to compare acute defibrillation success
      with a three-electrode configuration in humans using 50%/50% versus 65%/65% tilt
      truncated exponential, biphasic waveforms delivered through a 110-microF
      capacitor. Acute DFTs for biphasic waveforms with 50%/50% versus 65%/65% tilt
      were measured in random order in 60 patients using a binary search method. The
      electrode configuration consisted of a RV coil as the cathode, and a SVC coil
      plus a pectoral active can emulator (CAN) as the anode. The waveforms were
      derived from an external voltage source with 110-microF capacitance, and the
      leading edge voltage of phase 2 was equal to the trailing edge voltage of phase
      1. Stored energy DFT (9.2 +/- 5.7 [50%/50%] vs 10.8 +/- 6.4 [65%/65%] J, P =
      0.007), current DFT (10.9 +/- 4.0 [50%/50%] vs 12.0 +/- 4.4 [65%/65%] A, P =
      0.002) and voltage DFT (391 +/- 118 [50%/50%] vs 424 +/- 128 [65%/65%] V, P =
      0.004) were significantly lower for the 50%/50% tilt waveform versus the 65%/65%
      tilt waveform using this three-electrode configuration and a 110-microF
      capacitor. For an RV(-)/SVC plus CAN(+) electrode configuration and a 110-microF
      capacitor, a 50%/50% tilt biphasic waveform results in a 15% reduction in energy
      DFT, 9% reduction in current DFT, and 8% reduction in voltage DFT versus a
      65%/65% tilt biphasic waveform.

PMID- 11227973
TI  - Clinical predictors and efficacy of antitachycardia pacing in patients with
      implantable cardioverter defibrillators: the importance of the patient's sex.
AB  - The ICD has become accepted as primary therapy for malignant ventricular
      arrhythmias. The incorporation of antitachycardia pacing into ICDs has provided a
      better tolerated alternative to shocks but has the potential disadvantage of
      delaying definitive therapy. Accordingly, we sought to delineate the
      characteristics of patients likely to experience unsuccessful termination of
      pacing and to identify ineffective pacing strategies. Of 519 patients who
      received ICDs, 11 clinical and tachycardia characteristics in the 162 who
      received antitachycardia pacing therapy for sustained ventricular arrhythmias
      were evaluated. Tachycardia episodes were grouped according to outcome of pacing
      (successful, unsuccessful, acceleration). Of 1,946 episodes, 1,502 (77.2%) were
      successfully reverted with pacing, 322 (16.5%) were unsuccessful, and 121 (6.2%)
      were accelerated. Antitachycardia pacing was less successful in women, patients
      with a history of myocardial infarction, those with more severe left ventricular
      dysfunction, those who received antiarrhythmic drugs, and those programmed to
      ramp pacing. Tachycardia acceleration was inversely related to tachycardia cycle
      length and was more frequent in patients programmed to more aggressive ramp
      pacing protocols. Women had an almost threefold incidence of tachycardia
      acceleration compared with men (14% vs 5%, P < 0.001). Antitachycardia pacing is
      generally successful in terminating ventricular tachycardia and has a low
      incidence of tachycardia acceleration. Caution should be used with rapid
      tachycardias and aggressive ramp pacing protocols because of an increased risk of
      acceleration. Antitachycardia pacing appears less successful and has a higher
      incidence of complications in women.

PMID- 11227974
TI  - Effect of lead exclusion for the manual measurement of QT dispersion.
AB  - To investigate the effect of different lead exclusion criteria for the manual
      measurement of QT dispersion (QTd). Simultaneous 12-lead ECGs from three groups
      of 25 subjects were studied; healthy normal subjects, subjects with a myocardial
      infarction, and subjects with arrhythmias. Leads were excluded with (1) small
      absolute T wave amplitudes, (2) small relative T wave amplitudes, and (3) small
      and/or large relative QT measurements. QTd was calculated as the QT range and
      assessed for its ability to differentiate between the normal and pathological
      groups. With exclusion of no leads or low absolute amplitude T waves (< 50
      microV) significant differences were observed only between normal and myocardial
      infarct groups (P < 0.05). Significant differences between normal and both
      pathological groups were observed when excluding the lead with the smallest
      amplitude T wave or shortest QT (P < 0.05), or when two leads of either type were
      excluded (P < 0.005). There was good agreement between leads excluded by
      amplitude or QT (P < 0.01). Lead exclusion for QTd is important. Exclusion of the
      two smallest amplitude or two shortest QT leads from each subject produced the
      greatest differences between the normal and pathological groups.

PMID- 11227976
TI  - Sunao Tawara: a father of modern cardiology.
AB  - Knowledge of the conduction system of the heart was greatly advanced by Tawara's
      work carried out in Aschoff's laboratory in Marburg at the beginning of this
      century. In his monograph, The Conduction System of the Mammalian Heart,
      published in 1906, Tawara indicated that the treelike structure of specific
      muscle fibers comprising the atrioventricular node, His bundle, bundle branches,
      and Purkinje fibers served as the pathway for atrioventricular conduction of
      excitation in the mammalian heart. From his own anatomic and histological
      findings of the conduction system, he assumed precisely that the conduction
      velocity of excitation in the system, except in the atrioventricular node, would
      be fast and that contraction as the result of excitation would take place at the
      various sites of the ventricles almost simultaneously. According to Tawara, a
      long pathway to each contracting unit and a fast conduction velocity of
      excitation would be a prerequisite for the effective contraction of the
      ventricles. Tawara's findings and assumptions provided Einthoven the theoretical
      basis for interpreting the electrocardiogram, resulting in rapid popularization
      of electrocardiography. This century has witnessed the rapid progress of
      cardiology, including cardiac pacing and its related sciences. This progress has
      its roots in the discovery of the conduction system and the development of
      electrocardiography that took place almost in the same period at the beginning of
      this century. Tawara's pioneering work on the conduction system still serves as
      an invaluable reference for basic and clinical research.

PMID- 11227975
TI  - Feasibility and initial results of an Internet-based pacemaker and ICD pulse
      generator and lead registry.
AB  - The medical community has no independent source of timely information regarding
      the performance of pacemaker and ICD pulse generators and leads. Accordingly, the
      authors established an Internet-based registry of pacemaker and ICD pulse
      generator and lead failures (www.pacerandicregistry.com). During the first year,
      they found three previously unreported device problems that were promptly
      communicated to the participants. Of the failures reported, 11% of ICD and 10% of
      pacemaker pulse generator failures were heralded by signs other than the expected
      elective replacement indicator (ERI). Average ICD battery longevity was 4.0 +/-
      0.7 years, and average dual chamber pacemaker battery longevity was 6.8 +/- 2.6
      years. Disrupted insulation accounted for 54% of pacemaker and 29% of ICD lead
      failures. Compared to pacemaker pulse generator and lead failure, ICD device
      failures were more likely to cause severe clinical consequences. In conclusion,
      an Internet-based registry is feasible and capable of providing timely data
      regarding the signs, causes, and clinical consequences of pacemaker and ICD
      failures.

PMID- 11227977
TI  - Transvenous low energy internal cardioversion for atrial fibrillation: a review
      of clinical applications and future developments.
AB  - Low energy internal atrial cardioversion can be performed by delivering biphasic
      shocks between transvenous catheters positioned within the cardiac chambers or
      great vessels. Delivery of shocks results in effective cardioversion at energies
      < 6-10 J and the procedure can be effective even when external cardioversion has
      failed. Shock induced discomfort varies from patient to patient, but the
      procedure can be usually performed without general anesthesia and eventually
      under mild sedation. Nevertheless, tolerability has to be improved by obtaining a
      substantial reduction in defibrillating thresholds. With regard to safety,
      delivery of shocks for defibrillating the atria implies a potential risk of
      inducing ventricular fibrillation; to minimize this risk, shock delivery must be
      synchronous to the QRS and should be avoided during rapid RR cycles (< 300 ms).
      Presently, transvenous low energy cardioversion is an investigational procedure,
      but a widening of indications is expected in the near future. The cost of the
      procedure, which remains invasive and requires a brief hospital stay, must be
      balanced with the benefit of restoring sinus rhythm and the possibility of
      maintaining sinus rhythm for the medium- to long-term. Experimental and clinical
      investigations of low energy internal cardioversion have resulted in the
      development of devices for atrial defibrillation whose clinical role and cost
      benefit ratio is currently under evaluation.

PMID- 11227978
TI  - Physical activity in the prevention of cardiovascular disease: an epidemiological
      perspective.
AB  - This review of the epidemiological evidence regarding physical activity and
      cardiovascular disease (CVD) provides substantial evidence from many different
      populations that leisure time physical activity is associated with reduced risk
      of coronary heart disease (CHD) and cardiovascular mortality in both men and
      women and in middle-aged and older individuals. Physical activity appears to be a
      critical factor in both primary and secondary prevention of CHD. The studies
      indicate a dose-response relationship between overall physical activity and CVD,
      which is linear at least up to a certain level of activity. Prospective studies
      suggest that physical activity is also associated with reduced risk of stroke.
      The mechanisms underlying the protective effect of physical activity on CVD are
      still unclear. In recent years. the view that physical activity has to be
      vigorous to achieve a reduction in risk of CHD has been questioned. Overall, the
      evidence points to the benefit of continued regular moderate physical activity
      which does not need to be strenuous or prolonged and includes daily leisure
      activities such as walking or gardening which are readily attainable by large
      sections of the population. Taking up regular light or moderate physical activity
      in middle or older age confers significant benefit for CVD and all-cause
      mortality.

PMID- 11227980
TI  - Interval training for performance: a scientific and empirical practice. Special
      recommendations for middle- and long-distance running. Part II: anaerobic
      interval training.
AB  - Studies of anaerobic interval training can be divided into 2 categories. The
      first category (the older studies) examined interval training at a fixed work
      rate. They measured the time limit or the number of repetitions the individual
      was able to sustain for different pause durations. The intensities used in these
      studies were not maximal but were at about 130 to 160% of maximal oxygen uptake
      (VO2max). Moreover, they used work periods of 10 to 15 seconds interrupted by
      short rest intervals (15 to 40 seconds). The second category (the more recent
      studies) asked the participants to repeat maximal bouts with different pause
      durations (30 seconds to 4 to 5 minutes). These studies examined the changes in
      maximal dynamic power during successive exercise periods and characterised the
      associated metabolic changes in muscle. Using short-interval training, it seems
      to be very difficult to elicit exclusively anaerobic metabolism. However, these
      studies have clearly demonstrated that the contribution of glycogenolysis to the
      total energy demand was considerably less than that if work of a similar
      intensity was performed continuously. However, the latter studies used exercise
      intensities that cannot be described as maximal. This is the main characteristic
      of the second category of interval training performed above the minimal velocity
      associated with VO2max determined in an incremental test (vVO2max). Many studies
      on the long term physiological effect of supramaximal intermittent exercise have
      demonstrated an improvement in VO2max or running economy.

PMID- 11227982
TI  - [Psychosocial factors and depressive disorders: pathogenesis model and
      intervention strategies].
AB  - This article gives an overview of the impact of psychosocial factors on the
      manifestation and course of depressive disorders. It focusses primarily on the
      large body of work done by G.W. Brown and his co-workers since the 1970s on the
      pathogenesis of depression. A systematic approach to the treatment of depression
      should contain not only specific psychotherapy as well as antidepressant drug
      treatment, but should also include interventions of a psychosocial nature. There
      are so far hardly any controlled studies in this area. So-called "befriending"
      projects and psychosocial support schemes for at-risk groups, e.g. single
      mothers, promise to be interesting approaches. Befriending in this context means
      a specific kind of relationship that differs structurally from the relationship
      between a therapist and his client. Interventions of this type on the basis of
      the prevalence of depressive disorders could have a substantial impact on public
      health.

PMID- 11227981
TI  - Challenges and opportunities for measuring physical activity in sedentary adults.
AB  - Increasing the physical activity of typically sedentary adult populations is at
      the forefront of the public health agenda. This review addresses the challenges
      in defining and measuring physical activity in this target group, for a number of
      purposes, namely, scientific or academic inquiry, surveillance, clinical
      application and programme evaluation. First, we clarify the conceptual
      distinctions between the terms sedentarism, physical inactivity, physical
      activity and energy expenditure. Next, we review and compare the utility of
      different approaches for quantifying and expressing physical activity in these
      populations. Physical activity in typically sedentary populations is most likely
      a simple pattern of behaviour that has been largely obscured by existing measures
      and its expression as energy expenditure. Existing self-report methods are
      practical, but suffer from floor effects and recall bias. Walking, the most
      important activity to assess in this target group, is very difficult to measure
      through self-report methods. Motion sensors are more appropriate for quantifying
      physical activity behaviours in typically sedentary populations. Of the 2 types
      of motion sensors - the accelerometer and the pedometers--the latter is more
      appealing because it is both an affordable and a 'good enough' measure of
      physical activity, specifically ambulatory activity. Although a common
      measurement approach would greatly facilitate our understanding of physical
      activity behaviour patterns, the selection of an approach ultimately depends on
      the purpose of the study and to a great extent, its budget. Researchers,
      clinicians and practitioners interested in accurately capturing the lower end of
      the continuum of physical activity (that is characteristic of sedentary
      populations) must thoughtfully consider the relative advantages and disadvantages
      of the available approaches.

PMID- 11227983
TI  - [Activation of resources in elderly depressed patients. An overview of current
      knowledge].
AB  - Psychotherapeutic research has empirically proven the activation of resources to
      be a primary and pervasive activating principle. Equally empirically
      substantiated is psychotherapy with the aged. In the present article, the
      specific application of resources activation in psychotherapy for old-age
      depression is particularly emphasized and attempts at defining the concept of
      resources as well as hints towards the discovery of resources are explored.
      Contrary to earlier assumptions that ageing is a deficiency process, it has now
      been shown that despite evident losses in various life areas in aging, some
      resources can be defined which can be decisive for a sense of well-being among
      the elderly and for prophylaxis or therapy of old-age depression. Procedures and
      resource activation with content must be activated in parallel with problem
      actualization so that feelings of self-esteem and well-being increase, problems
      are solved and experiences of loss due to ageing are compensated. One of the most
      important resources among the elderly has proved to be the ability to accommodate
      and the social network. Group therapy as an effective and economical form of
      therapy as well as the therapeutic relationship itself can be employed as
      resources to promote social interaction among the aged.

PMID- 11227984
TI  - [Psychiatric inpatient length of stay. An overview of methods, influences and
      consequences].
AB  - Duration of inpatient psychiatric treatment is considerably under discussion
      between hospitals and payers. This article aims at reviewing the scientific
      evidence on the topic of psychiatric inpatient duration of stay. Two general
      research questions can be identified from the literature: 1. Which factors do
      influence duration of stay? 2. Which consequences does duration of psychiatric
      treatment have on patients' health status? Results show that duration of stay is
      less influenced by psychiatric diagnosis and sociodemographic items but more by
      the process of treatment and by organizational characteristics of the
      institutions. More recent studies generally find positive effects of longer
      treatment episodes. Studies about the consequences of duration of stay show a
      relation between reductions in duration of treatment and increasing readmissions.
      It is concluded that reductions in duration of inpatient treatment must be
      carefully evaluated to prevent negative consequences for patients' health status.

PMID- 11227979
TI  - The cytokine response to physical activity and training.
AB  - Cytokines are soluble glycoproteins that are produced by and mediate
      communication between and within immune and nonimmune cells, organs and organ
      systems throughout the body. Pro- and anti-inflammatory mediators constitute the
      inflammatory cytokines, which are modulated by various stimuli, including
      physical activity, trauma and infection. Physical activity affects local and
      systemic cytokine production at different levels, often exhibiting striking
      similarity to the cytokine response to trauma and infection. The present review
      examines the cytokine response to short term exercise stress, with an emphasis on
      the balance between pro- and anti-inflammatory mechanisms and modulation of both
      innate and specific immune parameters through cytokine regulation. The effects of
      long term exercise on cytokine responses and the possible impact on various
      facets of the immune system are also discussed, with reference to both cross
      sectional and longitudinal studies of exercise training. Finally, the validity of
      using exercise as a model for trauma and sepsis is scruti- nised in the light of
      physiological changes, symptomatology and outcome, and limitations of the model
      are addressed. Further studies, examining the effect of exercise, trauma and
      infection on novel cytokines and cytokine systems are needed to elucidate the
      significance of cytokine regulation by physical activity and, more importantly,
      to clarify the health implications of short and long term physical activity with
      respect to overall immune function and resistance to infection.

PMID- 11227986
TI  - [Word generation in bilinguals--fMRI study with implications for language and
      memory processes].
AB  - For over a century the cerebral representation of language functions is a matter
      of debate. In Neuroscience language is regarded as one of the most lateralized
      cognitive functions. Thus, while the language which is acquired first in most
      cases is processed by the left hemisphere some studies in brain damaged but also
      experimental investigations propose a pivotal role of the right hemisphere in
      second language processing. By the advent of modern neuroimaging it is now
      possible to study language lateralization and bilinguality also in healthy
      subjects. We studied first and second language abilities in a group of bilingual,
      healthy individuals by means of functional magnetic resonance imaging (fMRI) with
      a word-fluency paradigm. While we found a predominantly left prefrontal activity
      during both first and also second language processing an additional right
      prefrontal activation was registered during the use of second language. Our
      findings are discussed on the basis of an interaction between language and memory
      processes.

PMID- 11227985
TI  - [Verbal memory disorders provoked by a variety of stokes].
AB  - In recent years a consensus has been reached about the neuroanatomical substrate
      of verbal memory, but this state of knowledge has not yet been implemented in
      clinical practice. One reason for this may be that most of the neuroscientific
      studies on verbal memory used different neuropsychological instruments and that
      only a small set of patient groups with the same etiology but different lesion
      sites were analysed. Returning to three earlier studies, we analyse the
      possibility to make differential judgements on the verbal memory impairments of
      four different patient groups by using the California Verbal Learning Test
      (CVLT). We compare patients with left-sided (n = 16) and right-sided (n = 10)
      posterior cerebral artery infarcts and patients with infarcts of the left (n =
      10) or right (n = 21) frontal lobe, and we integrated data about their retention
      errors that had not been analysed so far. Our findings reveal significant
      differences between these patient groups, concerning the quantitative aspects of
      impairments, and also the profiles of memory errors (recall, interference and
      perseverations). Our study documents a relation between the site of the lesion
      and the type of verbal memory impairment, agreeing with some of the most recent
      neuroscientific findings. Starting from this observation we try to define a
      neuropsychological pattern of memory impairment which enables differential
      clinical diagnoses using the CVLT as a memory test.

PMID- 11227987
TI  - Utility of the Pediatric Symptom Checklist for behavioral screening of
      disadvantaged children.
AB  - Investigated the utility of a parent report measure designed specifically for
      behavior screening in the pediatric primary care setting for use with
      disadvantaged children and families. Results indicated that the Pediatric Symptom
      Checklist was significantly related to scores derived from the Child Behavior
      Checklist. Receiver Operator Characteristic analysis indicated the need for
      modification of the cutting score previously established with middle-class
      children. A model for screening children for psychopathology within the
      structural-organizational constraints of the pediatric primary care setting is
      presented.

PMID- 11227988
TI  - Family environment, child behavior, and medical indicators in children with
      kidney disease.
AB  - Effects of family environment on child behavior symptoms and medical indicators
      in children with one of three kidney diseases were examined. Parents (n = 41) of
      children with nephrotic syndrome, chronic renal insufficiency, or kidney
      transplant completed family environment and child behavior questionnaires.
      Medical indicators (utilization and medications) were collected from medical
      records. A model including child age, diagnostic group, and family environment
      variables successfully predicted all outcomes except internalizing behavior.
      Higher family conflict predicted more externalizing symptoms and higher number of
      prescribed medications; higher family cohesion predicted fewer hospitalizations.
      Nontraditional family structure predicted higher number of prescribed
      medications. Results are discussed as they relate to a stress and resistance
      framework, need for research on direction of effect, and clinical
      recommendations.

PMID- 11227989
TI  - Substance abuse and criminal recidivism: a prospective study of adolescents.
AB  - Studies of substance abuse among delinquents have shown mixed results on criminal
      recidivism. The present study evaluates personality traits associated with
      substance abuse and recidivism among delinquent boys, and prospectively
      determines the extent to which these factors are predictive of criminal
      recidivism. 134 incarcerated boys (x = 15.9 +/- 1.1) completed the Weinberger
      Adjustment Inventory and the Substance Abuse Screening Inventory. Youth were
      prospectively followed for up to 4.5 years following release. Among incarcerated
      delinquents, personality traits are predictive of a positive substance abuse
      screen and recidivism. A trend indicating a possible interaction between
      personality and treatment is observed. If these findings are replicated,
      personality traits may play a role in predicting substance abuse as well as
      individual delinquent responses to treatment.

PMID- 11227990
TI  - Perceptions and attitudes toward prenatal cocaine exposure in young children.
AB  - OBJECTIVE: This paper investigated perceptions and attitudes toward young
      children believed to be prenatally exposed to cocaine. METHOD: 37 college
      students watched a videotape of eight children doing the same task and rated each
      child's performance after being told if the child had, might have been, or had
      not been prenatally exposed to cocaine. RESULTS: Multiple analysis of variance
      confirmed that when a child was labeled prenatally exposed to cocaine, the
      participants generally scored the child lower and less positively than it the
      child was thought to be possibly exposed or not exposed at all. Ethnicity and
      gender differences were also found. Participants rated males higher than females
      and African-American children higher than Caucasian children. CONCLUSIONS:
      Individuals who believe a child is exposed prenatally to cocaine hold more
      negative perceptions regarding that child's developmental abilities. These
      negative perceptions of a child labeled prenatally exposed to cocaine may
      diminish expectations for that child's developmental potential.

PMID- 11227992
TI  - Correlation between intracellular pharmacological activation of nucleoside
      analogues and HIV suppression in vitro.
AB  - Following intracellular activation of HIV nucleoside analogue reverse
      transcriptase inhibitors, their triphosphates (ddNTPs) compete with endogenous
      nucleoside triphosphates (dNTPs) for incorporation into proviral DNA. In this
      study we have examined the effect of combinations of two thymidine analogues,
      stavudine (d4T) and zidovudine (ZDV), and two cytidine analogues, lamivudine
      (3TC) and zalcitabine (ddC) on intracellular drug activation and on the relevant
      competing dNTP in uninfected and persistently HIV-infected cells. Endogenous
      triphosphates of deoxycytidine (dCTP) and deoxythymidine (dTTP) were measured
      using a template primer assay and the ratio of ddNTP:dNTP was calculated.
      Antiviral activity of two-drug combinations was also assayed by p24 ELISA. A
      significant reduction in d4T triphosphate (d4TTP) [0.11+/-0.09 pmol/10(6) cells
      to undetectable (<0.01); P=0.039] in the presence of equimolar concentrations of
      ZDV and d4T, resulted in a decrease in the d4TTP/dTTP ratio of 90%. ZDVTP/dTTP
      was not significantly altered in the presence of d4T. 3TC (10 microM) reduced
      total ddC phosphates by 57% and ddCTP/dCTP by 27%. 3TC phosphorylation was
      comparatively unaffected by ddC, up to a concentration of 10 microM ddC (>100
      times the plasma concentration achieved following standard dosing). 3TC plus ddC
      resulted in greater p24 inhibition than 3TC or ddC alone (P<0.001). Combining one
      thymidine analogue (ZDV or d4T) with one cytidine analogue (3TC or ddC) resulted
      in greater inhibition of p24 inhibition than with any single agent. From a
      pharmacological viewpoint, the combination of ZDV plus d4T should be avoided, but
      in vitro the combination of 3TC plus ddC confers modest benefit over either drug
      alone. This in vitro study illustrates that decreases in ddNTP/dNTP are
      consistent with a reduction in antiviral effect.

PMID- 11227991
TI  - Cognitive development, temperament and behavior at 2 years as indicative of
      language development at 4 years in pre-term infants.
AB  - This study focuses on the early temperamental (TTQ = toddler temperament
      questionnaire), behavioral (IBR = infant behavior record), and cognitive
      precursors of impaired language functioning in preschool-age pre-terms infants.
      The study group consisted of 63 pre-term infants with a mean birth weight of 1246
      +/- 437 g born in 1989-1991 in the University Central Hospital of Helsinki.
      Children with major disabilities (CP or mental retardation) were excluded. At the
      age of 4 years, 22% showed impaired language function. Logistic regression
      analysis showed that the Bayley MDI score was the best predictor in identifying
      an increased risk for language impairment. Behavioral characteristics were more
      strongly associated with subsequent language impairment than temperament.

PMID- 11227994
TI  - Antiviral activity of mixed-valence rare earth borotungstate heteropoly blues
      against influenza virus in mice.
AB  - The acute and accumulated toxicity of the rare earth borotungstate heteropoly
      blues, HPB-2, Ce2H3[BW9(VI)W2(V)Mn(H2O)O39].12H2O, which is active against
      influenza virus in Kunming mice, were investigated in Kunming mice following oral
      and intraperitoneal administration. The activity of HPB-2 against influenza virus
      (FM1) in the mice was then investigated. HPB-2, given either orally (p.o.) or
      intraperitoneally (i.p.), was shown to have activity. HPB-2 was shown to be more
      effective than the positive control, ribavirin, and it was also found that i.p.
      administration was more effective than p.o. administration.

PMID- 11227993
TI  - Selection of resistance-conferring mutations in HIV-1 by the nucleoside reverse
      transcriptase inhibitors (+/-)dOTC and (+/-)dOTFC.
AB  - The patterns of resistance-conferring mutations that are selected in HIV-1
      reverse transcriptase (RT) by the racemates of 2'-dideoxy-3'-oxa-4'-thiocytidine
      (+/-)dOTC and its fluorinated derivative (+/-)dOTFC were characterized. Genotypic
      and phenotypic analyses of HIV-1 clinical isolates and HXB2D variants selected
      with (+/-)dOTC and (+/-)dOTFC were performed in primary cells and in the MT-2 T
      cell line. HIV-1 variants selected with (+/-)dOTC or (+/-)dOTFC displayed
      fivefold decreased susceptibility to the respective compounds. A substitution of
      methionine to valine was identified at position 184 (M184V) in variants selected
      with (+/-)dOTC. In contrast, a mutation of lysine to arginine at position 65
      (K65R) was found in variants selected with (+/-)dOTFC. These patterns of selected
      mutations differ from those seen with the individual enantiomers. Studies with
      mutated recombinant HXB2D-M184V and -K65R confirmed that these mutations are
      important for phenotypic resistance in MT-2 cells. Clinical isolates that display
      resistance to (-)2'-deoxy-3'-thiacytidine (3TC) also showed cross-resistance to
      (+/-)dOTC and (+/-)dOTFC. These studies demonstrate that similar genotypes may be
      selected by the dOTC and dOTFC compounds to those with the structurally related
      drug 3TC.

PMID- 11227995
TI  - Synthesis and anti-rhinovirus activity of 2-styrylchromones.
AB  - 2-Styrylchromones were synthesized as vinylogues of 2-phenylchromones (flavones),
      a broad class of anti-rhinovirus compounds. The antiviral activity of 2
      styrylchromones and 3-hydroxy-1-(2-hydroxyphenyl)-5-phenyl-2,4-pentadien-1-ones,
      which are intermediates in the synthesis, was evaluated against two selected
      serotypes of human rhinovirus, 1B and 14, by a plaque reduction assay in HeLa
      cell cultures. All of the compounds interfered with HRV 1B replication, with the
      exception of 3-hydroxy-1-(2-hydroxyphenyl)-5-(4-methoxyphenyl)-2,4-pentadien-1
      one. The majority of derivatives were also found to be effective against serotype
      14, often with a higher potency.

PMID- 11227996
TI  - Synthesis and anti-varicella-zoster virus activity of some novel bicyclic
      nucleoside inhibitors: effect of enhanced aqueous solubility.
AB  - We have recently reported the discovery of an entirely new category of potent
      antivaricella-zoster virus agents based on novel deoxynucleoside analogues
      bearing unusual fluorescent bicyclic furo base moieties. Initial studies revealed
      an absolute requirement of a long alkyl side-chain, with an optimal length of C8
      C10, for antiviral activity. However, the impact of this requirement on the
      physical properties of these compounds is high: inherent lipophilicity and
      extremely poor aqueous solubility, which may limit the use of these nucleosides
      as drugs. In order to address this issue, we have now prepared a new series of
      analogues, bearing ether and glycol type side-chains, designed to improve the
      aqueous solubility of the compounds. Synthesis of target nucleosides involved Pd
      catalysed coupling of terminal alkynes with 5-iodo-2'-deoxyuridine. The 5-alkynyl
      nucleosides thus obtained were then treated with copper (I) iodide to produce the
      desired bicyclic analogues. As anticipated, the new compounds exhibited a
      dramatic increase in aqueous solubility, although antiviral activity was
      significantly reduced. A possible correlation between antiviral activity and
      overall compound lipophilicity is discussed.

PMID- 11227997
TI  - Immunoepidemiology--bridging the gap between immunology and epidemiology.
AB  - 'Immunoepidemiology' combines individual- and population-oriented approaches to
      create new perspectives. It examines how inter-individual differences in immune
      responses affect the population dynamics of micro- and macro-parasites to produce
      the epidemiological patterns of infection observed in heterogeneous host
      populations. Here, I discuss how research has only just begun to tap the
      potential of this integrative discipline that incorporates immunology,
      parasitology, genetics, epidemiology, ecology, mathematical modelling and
      statistics.

PMID- 11227999
TI  - Genetics and malaria--more questions than answers.

PMID- 11228000
TI  - Parasites of pet animals: progress and new hazards.

PMID- 11228002
TI  - Leishmania virulence: it's a knock out!

PMID- 11228001
TI  - Natural products for the treatment of tropical diseases.

PMID- 11228003
TI  - Sticky rings: challenging the cytoadherence dogma.

PMID- 11228004
TI  - Fahrenheit-based forecasts for falciparum could be false.

PMID- 11228005
TI  - Schistosomiasis-induced IL-10 suppresses allergy prevalence.

PMID- 11228006
TI  - Recombining trypanosome genetics.

PMID- 11228007
TI  - More panantigens in Leishmania.

PMID- 11228008
TI  - More panantigens in Leishmania.

PMID- 11228009
TI  - Revisiting amebiasis.

PMID- 11228010
TI  - Revisiting amebiasis.

PMID- 11228011
TI  - Bird schistosomes: do they die in mammalian skin?
AB  - The cercariae of bird schistosomes, released from the intermediate water snail
      host, actively penetrate the skin of both birds and mammals. Whereas in birds the
      infection leads to worm maturation and egg production, in the mammalian hosts
      skin invasion is accompanied by cercarial dermatitis (swimmer's itch, clam
      digger's disease) and the fate of the parasites is not clear. Here, we review
      bird schistosomes as causative agents of cercarial dermatitis, underline
      adaptations of bird schistosomes to their life in vertebrate hosts, and discuss
      potential risks caused by the parasites migrating in humans.

PMID- 11228012
TI  - Are inflammation and immunological hyperactivity needed for filarial parasite
      development?
AB  - Immune-dependent growth and development of infectious agents and pathogenesis of
      disease are increasingly being recognized. It is proposed that the development of
      filarial larvae to adult stage parasites takes place in an ambiance of
      inflammatory T helper cell type 1 cytokines in mammalian hosts, and that
      susceptibility to filarial infections could be governed by the status of
      macrophage-derived nitric oxide and host ability to produce antibodies to
      filarial T-independent (carbohydrate) antigens.

PMID- 11228013
TI  - Tick-borne infectious diseases of dogs.
AB  - Tick-transmitted infections are an emerging problem in dogs. In addition to
      causing serious disease in traditional tropical and semi-tropical regions, they
      are now increasingly recognized as a cause of disease in dogs in temperate
      climates and urban environments. Furthermore, subclinically infected companion
      animals could provide a reservoir for human tick-transmitted infectious agents,
      such as Ehrlichia chaffeensis, Ehrlichia ewingll, the Ehrlichia phagocytophila
      group and Rickettsia conorii. Here, we discuss the emergence of new canine tick
      transmitted diseases, which results from several factors, including the expansion
      of the tick range into urban and semi-urban areas worldwide, the movement of
      infected dogs into previously non-endemic areas, and the advent of novel
      molecular techniques for diagnosis and pathogen identification.

PMID- 11228014
TI  - Mix and match modules: structure and function of microneme proteins in
      apicomplexan parasites.
AB  - Microneme organelles are found in the apical complex of all apicomplexan
      parasites and play an important role in the invasion process. The recent
      identification of microneme proteins from different apicomplexan genera has
      revealed a striking conservation of structural domains, some of which show
      functional complementation across species. This supports the idea that the
      mechanism of host cell invasion across the phylum is conserved not only
      morphologically, but also functionally at the molecular level. Here, we review
      and summarize these recent findings.

PMID- 11228015
TI  - Inherited microorganisms, sex-specific virulence and reproductive parasitism.
AB  - Parasites show an amazing repertoire of adaptations, highlighted by complex life
      cycles that allow both survival in the host and transmission among hosts.
      However, there is one heterogeneous group of microorganisms whose adaptations are
      perhaps even more surprising: parthenogenesis induction, feminization of genetic
      males, killing of male hosts and sperm-mediated sterilization of uninfected eggs.
      The common feature of these microorganisms is their mode of transmission:
      inheritance from mother to offspring. Here, we present an introduction to
      hereditary symbiosis, focusing on microsporidia and bacteria that manipulate host
      reproduction in arthropods (reproductive parasites). We also discuss the
      implications of one of these microorganisms, Wolbachia, for the control of
      arthropod pests and vectors and for the therapy of filarial diseases. Finally, we
      discuss whether some parasites of vertebrates might show sex-specific virulence.

PMID- 11228018
TI  - Physician as listener.

PMID- 11228016
TI  - Malaria early warning in Kenya.
AB  - Kenya displays large spatiotemporal diversity in its climate and ecology. It
      follows that malaria transmission will reflect this environmental heterogeneity
      in both space and time. In this article, we discuss how such heterogeneity, and
      its epidemiological consequences, should be considered in the development of
      early warning systems for malaria epidemics.

PMID- 11228017
TI  - Trypanosoma vivax--out of Africa.
AB  - Trypanosoma vivax is a blood parasite of ruminants that was introduced into Latin
      America in cattle imported from Africa, possibly in the late 19th century. The
      parasite has now spread to ten of the 13 countries of the South American
      continent, often resulting in a severe wasting disease and death. Here, we review
      the current state of knowledge about this parasite and the problems faced by
      animal health agencies in controlling the disease.

PMID- 11228019
TI  - Getting active about physical education.

PMID- 11228020
TI  - Cause of distress.

PMID- 11228021
TI  - Moonlighting by residents.

PMID- 11228022
TI  - The forgotten refugees.

PMID- 11228023
TI  - Effects of prenatal exposure to marijuana.
AB  - QUESTION: I am treating a 27-year-old woman who is now in her 10th week of
      pregnancy. She smokes marijuana two to three times a week, but does not use other
      drugs. She also smokes 20 cigarettes a day. I am concerned about the effects of
      marijuana exposure on her baby. ANSWER: It is not always possible to isolate the
      effect of marijuana exposure from other possible confounders on pregnancy
      outcome. Although marijuana is not an established human teratogen, recent well
      conducted studies suggest it might have subtle negative effects on
      neurobehavioural outcomes, including sleep disturbances, impaired visual problem
      solving, hyperactivity, impassivity, inattention, and increased delinquency.

PMID- 11228024
TI  - Ophthaproblem. Lattice corneal dystrophy.

PMID- 11228025
TI  - [Practical advice. Subcutaneous drug administration. An alternative used in
      palliative care].

PMID- 11228026
TI  - Just the Berries. Use of CPAP and BiPAP in acute respiratory failure.

PMID- 11228027
TI  - Do glucosamine and chondroitin treat the symptoms of osteoarthritis?

PMID- 11228028
TI  - [Evaluation of sphygmomanometers used by family physicians practicing outside the
      hospital environment in Bas-Saint-Laurent].
AB  - OBJECTIVE: To assess the precision and integrity of all aneroid and mercury
      sphygmomanometers regularly used by family physicians practising outside
      hospitals. DESIGN: Cross-sectional study. SETTING: Private medical clinics and
      local community health centres in Bas-Saint-Laurent, Que. PARTICIPANTS: A total
      of 151 of the 166 physicians in this administrative region. MAIN OUTCOME
      MEASURES: Precision of the mercury sphygmomanometers was measured using the
      difference between a reading in the absence of pressure and level 0. Precision of
      the aneroid sphygmomanometers was measured using variations at pressures of 140
      mm Hg and 90 mm Hg compared with those on a calibrated mercury sphygmomanometer.
      Integrity of sphygmomanometers, arm cuffs, and inflating bulbs was also assessed.
      RESULTS: In all, 258 sphygmomanometers met the inclusion criteria (111 mercury
      sphygmomanometers and 147 aneroid sphygmomanometers). Discrepancies of > or = 4
      mm Hg were found in 15.5% of these instruments (12.6% and 17.7% of the mercury
      and aneroid sphygmomanometers, respectively). In 31.0% of the instruments (52.3%
      and 15.0% of the mercury and aneroid sphygmomanometers, respectively), one
      component was malfunctioning. CONCLUSION: Sphygmomanometers that measure
      patients' blood pressure inaccurately could result in an incorrect diagnosis of
      hypertension or in a normal blood pressure reading in a hypertensive patient.

PMID- 11228029
TI  - Primary care in Bosnia and Herzegovina. Health care and health status in general
      practice ambulatory care centres.
AB  - OBJECTIVE: To assess the health care and health status of patients attending
      primary care clinics in Bosnia and Herzegovina. DESIGN: Assisted administration
      patient survey. SETTING: Two ambulatory care clinics (ambulantas) in each of
      three cities in Bosnia and Herzegovina: Tuzla, Mostar, and Banja Luka.
      PARTICIPANTS: Patients attending the ambulantas during a 1-week period in March
      1999; 885 answered questionnaires. MAIN OUTCOME MEASURES: Each patient listed
      demographic characteristics and answered questions on satisfaction with health
      care and with the physical and financial accessibility of health care services
      and medications. A validated health status questionnaire (EuroQoL), previously
      used in parts of the former Yugoslavia, was administered. RESULTS: Only 22% of
      patients were employed; 57% could not pay the nominal fee to see a physician; 71%
      walked to the clinic; mean distance from patients' homes to the clinics was 2.3
      km; 63% could not get the medications prescribed (in 85% of cases because of
      cost, not availability); 80% to 90% of answers to satisfaction questions
      suggested high satisfaction with the care patients received from their doctors;
      67% of the time patients were referred to a specialist by general practitioners;
      33% had problems walking; 17% had problems with self-care; 36% had problems with
      usual daily activities; 72% had at least some pain or discomfort; and 62%
      described at least some anxiety or depression. The three cities showed
      significant differences; patients in Tuzla generally had lower health status and
      more problems with health care. CONCLUSION: Unemployment and financial
      considerations reduced health care access in Bosnia and Herzegovina. While only
      one third of patients had physical difficulties, two thirds had emotional
      problems or pain. Satisfaction with physicians' care was high.

PMID- 11228030
TI  - Short report: reducing length of hospital stay for newborns in Saskatchewan. Is
      it safe?

PMID- 11228031
TI  - Lipid-lowering update 2001. Aggressive new goals.
AB  - OBJECTIVE: To review the central role of cholesterol in coronary artery disease
      (CAD), underscore the need for identifying patients at high risk of CAD, and
      discuss treatment of dyslipidemias. QUALITY OF EVIDENCE: Current literature (1995
      2000) was searched via MEDLINE using the MeSH headings "cholesterol," "risk
      reduction," and "statins." Recommendations in this paper are based mainly on the
      results of large randomized controlled trials. Preference was given to more
      recent articles, clinically relevant articles, and landmark clinical trials. MAIN
      MESSAGE: Lipid lowering, and specifically low-density lipoprotein lowering, has
      been repeatedly shown in large clinical trials to improve survival dramatically
      and reduce cardiac events in both primary and secondary prevention. Identifying
      those at highest risk for future cardiac events is critical because these
      patients will benefit most from aggressive modification of risk factors. The
      definition of high risk has been expanded to include patients with diabetes
      mellitus and peripheral vascular disease, as well as those with established CAD.
      A full lipid profile is required for these patients to assess risk and develop a
      lipid-lowering strategy with proven effectiveness. CONCLUSION: With the advent of
      powerful, efficacious, and well tolerated cholesterol-modifying therapies, lipid
      normalization should be a mandate for all physicians caring for patients with
      established CAD and patients at risk of developing CAD.

PMID- 11228032
TI  - Chronic occupational repetitive strain injury.
AB  - OBJECTIVE: To review common repetitive strain injuries (RSIs) that occur in the
      workplace, emphasizing diagnosis, treatment, and etiology of these conditions.
      QUALITY OF EVIDENCE: A MEDLINE search from January 1966 to June 1999 focused on
      articles published since 1990 because RSIs are relatively new diagnoses. MeSH
      headings that were explored using the thesaurus included "cumulative trauma
      disorder," "overuse injury," and "repetitive strain injury." The search was
      limited to English articles only, and preference was given to randomized
      controlled trials. MAIN MESSAGE: Repetitive strain injuries result from repeated
      stress to the body's soft tissue structures including muscles, tendons, and
      nerves. They often occur in patients who perform repetitive movements either in
      their jobs or in extracurricular activities. Common RSIs include tendon-related
      disorders, such as rotator cuff tendonitis, and peripheral nerve entrapment
      disorders, such as carpal tunnel syndrome. A careful history and physical
      examination often lead to the diagnosis, but newer imaging techniques, such as
      magnetic resonance imaging and ultrasound, can help in refractory cases.
      Conservative management with medication, physiotherapy, or bracing is the
      mainstay of treatment. Surgery is reserved for cases that do not respond to
      treatment. CONCLUSION: Repetitive strain injury is common; primary care
      physicians must establish a diagnosis and, more importantly, its relationship to
      occupation. Treatment can be offered by family physicians who refer to
      specialists for cases refractory to conservative management.

PMID- 11228033
TI  - Delivery systems for acute migraine medications.
AB  - OBJECTIVE: To discuss advantages and disadvantages of various routes of
      administration and delivery systems for acute migraine medications, and to assist
      family physicians in optimizing treatment for individual patients. QUALITY OF
      EVIDENCE: A MEDLINE search from January 1966 to October 2000 and a Current
      Contents search for the year 1999 to October 2000 were conducted. Randomized
      controlled trials were selected, when available. Also included are guidelines
      (Canadian), non-blinded trials, systematic reviews, and population-based studies.
      MAIN MESSAGE: Selecting an appropriate way to deliver medication is important in
      acute migraine therapy. The parenteral route has advantages, such as rapid onset,
      greater efficacy, and the possibility of use during nausea and vomiting.
      Disadvantages include local site discomfort, inconvenience, and patients' dislike
      of needles. Most patients prefer oral therapy, but gastric stasis and nausea and
      vomiting during a migraine attack might limit its use. The intranasal route
      usually provides fairly rapid onset, but side effects, such as disturbances in
      taste, can occur. The rectal route is another option, but absorption is sometimes
      erratic, rectal irritation can occur, and few migraine medications are available
      in rectal formulation. CONCLUSION: Selection of appropriate medications and
      suitable delivery systems for individual patients, based on the characteristics
      of their attacks (e.g., severity, speed of progression to severe intensity,
      degree of associated symptoms), ease of administration, and patient preference,
      will optimize therapy for acute migraine attacks.

PMID- 11228034
TI  - Rourke Baby Record 2000. Collaboration in action.

PMID- 11228035
TI  - Finding the right information at the right time. Part 1: Drugs, reference books,
      clinical practice guidelines.

PMID- 11228036
TI  - Corpses and maniacs: the loves of Dr James Douglas.

PMID- 11228037
TI  - National family medicine resident survey. Part 2: Future practice profile.

PMID- 11228038
TI  - Postpartum autoimmune thyroid syndrome.

PMID- 11228039
TI  - An assessment of diagnostic procedures preparatory to retroperitoneoscopic
      removal of adenoma in cases of primary hyperaldosteronism.
AB  - The goal of this study was to improve assessment of diagnostic measures for
      lateral localization of aldosterone-producing adrenal adenomas preparatory to
      retroperitoneoscopic removal, in view of the fact that this technique allows for
      only unilateral access. A retrospective study was carried out of the medical
      records of 64 patients (38 women, 26 men, average age 46.8+/-11.2) who underwent
      surgery at University Hospital, Munster, between 1969 and 1998. Seventeen of the
      64 patients presented with hyperplasia and 47 had adrenal adenoma. In cases of
      hyperplasia, computerized tomography imaged a false-positive unilateral tumor 10
      times, a false-negative 3 times, and a unilateral hyperplasia 1 time
      (ultrasonography: tumor 2 times, false-negative 3 times; 131I
      Iodomethylnorcholesterol scintigraphy: tumor 5 times, false-negative 1 time,
      correct 1 time). In cases of adenoma, computerized tomography yielded accurate
      results 40 times, imaged a false-negative 2 times, and indicated the incorrect
      side 1 time (Ultrasonography: false-negative 12 times, correct side 9 times,
      incorrect side 1 time; 131I-Iodomethylnorcholesterol scintigraphy: correct side
      19 times, false-positive (both sides) 5 times, negative 3 times, incorrect side 2
      times). Venous sampling, which was carried out seven times, yielded accurate
      results six times, and failed technically one time. Venous sampling appears to be
      the method of choice for preoperative lateral localization. Thus,
      retroperitoneoscopic treatment of Conn's syndrome should not be carried out
      unless venous sampling is carried out first.

PMID- 11228040
TI  - A case of isolated ACTH deficiency who developed autoimmune-mediated
      hypothyroidism and impaired water diuresis during glucocorticoid replacement
      therapy.
AB  - A case of isolated ACTH deficiency who developed autoimmune-mediated
      hypothyroidism and still showed impaired water diuresis during glucocorticoid
      replacement therapy is reported. A 45-year-old woman was initially admitted for
      nausea, vomiting, and general malaise. Her serum sodium and plasma osmolality,
      ACTH and cortisol values were low, but her urine osmolality was high. Other
      pituitary hormone levels, thyroid hormone levels, and a computed tomogram of the
      pituitary gland were normal. The patient was treated with hydrocortisone and
      followed in the outpatient clinic; however, she was lost to follow up 18 months
      after admission. Three years later she presented with hypoglycemia and
      hyponatremia. Her serum or plasma ACTH, FT3, FT4, cortisol levels were low and
      her serum TSH level was high. Pituitary stimulation tests revealed a blunted
      response of ACTH to CRH and an exaggerated response of TSH to TRH. Plasma ADH was
      inappropriately high, and a water-loading test revealed impaired water diuresis
      and poor suppression of ADH. Although ADH was suppressed, impaired water diuresis
      was observed in the water loading test after hydrocortisone supplementation.
      Thyroxine supplementation completely normalized the water diuresis. Her
      outpatient clinic medical records revealed a gradual increase in TSH levels
      during follow up, indicating that she had developed hypothyroidism during
      glucocorticoid replacement therapy. The hyponatremia on the first admission was
      due to glucocorticoid deficiency, whereas the hyponatremia on the second
      admission was due to combined deficiencies of glucocorticoid and thyroid
      hormones.

PMID- 11228041
TI  - Effects of hard tissue-related hormones on the intracellular calcium ion of the
      rat odontoblasts.
AB  - We examined the effects of PTH, calcitonin (CT) and parotin subunit on the
      intracellular Ca2+ of odontoblasts using a chelate reagent, FURA2-AM. Rat CT
      (rCT), at a final concentration of 0.01 microM, induced a gradual lowering of
      Ca2+, and addition of ATP, in the presence of CT, resulted in a partial and short
      lasting recovery of Ca2+. At higher concentrations, it caused a rapid decrease of
      Ca2+. CTs of other animal species showed similar effects. Human PTH (hPTH) added
      at concentrations of 0.01, 0.1 and 1 microM, caused no significant changes in
      intracellular Ca2+. Parotin subunit caused a rapid lowering of Ca2+ which was
      seen already at 0.01 microM. rCT added after treatment with hPTH caused an
      immediate decrease of Ca2+ to zero level, showing that CT action was enhanced by
      pretreatment with hPTH. This enhancement was also confirmed by addition of hPTH
      after rCT, where at 1 microM, it caused further acute decrease in Ca2+. After
      intracellular Ca2+ was lowered by CT pretreatment, parotin, at 0.1 microM,
      induced a further but gradual decrease of Ca2+. The present results, together
      with our previous study indicating that hPTH increased cAMP production and that
      CT inhibited the PTH action, made it clear that all the hormones affect
      odontoblasts, and that CT and parotin act via Ca-related signal transduction
      system, while PTH acts via cAMP-PKA-related cascade. Possible crosstalk of both
      systems was also suggested.

PMID- 11228042
TI  - Genetic analysis of two female patients with incomplete Denys-Drash syndrome.
AB  - Denys-Drash syndrome (DDS) is characterized by genital anomaly, early onset
      nephropathy and high risk for developing Wilms' tumor (WT). Recently, mutations
      in exon 8 or 9 of the Wilms' tumor suppressor gene (WT1) have been found in the
      majority of DDS patients studied. We analyzed these two exons of the WT1 gene in
      genomic DNA from two female patients with DDS by using polymerase-chain reaction
      (PCR) and direct sequencing. The patients were accompanied with normal external
      genitalia, early onset renal failure between 6 and 12 months of age, and
      unilateral Wilms' tumor. Genomic DNA was isolated from peripheral blood
      leucocytes of the patients. Amplification of exons 8 and 9 of the WT1 gene by PCR
      was performed, and direct sequencing of the PCR product was performed using an
      automatic DNA sequencer. Two heterozygous missense mutations were found in these
      patients, including a missense mutation in exon 9 at codon 388 replacing the wild
      type Cys with Phe, and a previously described mutation in exon 9 at codon 398
      replacing the wild-type Leu with Pro. Cys388Phe is a novel mutation in the WT1
      gene in the DDS. These cases are considered to be "incomplete DDS" with
      nephropathy and Wilms' tumor and without genital anomaly, the validity of which
      has been confirmed by mutation analysis.

PMID- 11228043
TI  - A unique case of central diabetes insipidus (DI) associated with transient
      pituitary stalk enlargement: close observation over several years using magnetic
      resonance imaging (MRI) and hypophysial endocrine tests.
AB  - We had the opportunity to closely observe a unique case of central diabetes
      insipidus (DI), in which dramatic changes in both radiological findings and
      hypophysial functions were seen. A 63-year-old female developed central DI, and
      magnetic resonance imaging (MRI) revealed a mild thickening of the pituitary
      stalk and lack of hyperintense signal associated with normal neurohypophysis on
      T1-weighted images. About three months later, the stalk was found to be
      remarkably expanded like neoplasm; however, anterior pituitary functions were
      almost normal on that occasion, except for the absence of GH response to an
      insulin tolerance test. About nine months after the onset of DI, secondary
      hypoadrenalism and hypothyroidism, which required replacement therapy, developed
      transiently, but recovered about one year later. Results of hypophysial endocrine
      tests during this period showed that the dysfunction was predominantly
      suprapituitary in nature. As time passed, the stalk lesion began to shrink
      spontaneously and another MRI, obtained five years after the onset of DI,
      disclosed normal findings for the infundibulo-hypophysial system, except for lack
      of the hyperintense signal of the neurohypophysis. The patient has since been
      healthy, except for the DI, which has been controlled by treatment with
      vasopressin. We report here a unique case of central DI associated with transient
      pituitary stalk enlargement.

PMID- 11228044
TI  - 17Beta-hydroxysteroid dehydrogenase type 2 and dehydroepiandrosterone
      sulfotransferase in the human liver.
AB  - The liver plays important roles in the clearance and metabolism of sex steroids.
      Its dysfunction is considered to influence the metabolic pathways of sex
      steroids, and to result in gynecomastia and other abnormalities of sex steroids.
      However, the details of its mechanism have not been well-characterized. We
      therefore examined the enzymes involved in the hepatic clearance and/or
      metabolism of sex steroids in human liver and its disorders using
      immunohistochemistry to determine whether there are any abnormalities of
      expression of these enzymes in human liver disorders. These enzymes are 17beta
      hydroxysteroid dehydrogenase (17beta-HSD) type 2, an enzyme that catalyzes the
      biologically active estrogen, estradiol (E2), to inactive estrogen, estrone (El),
      and dehydroepiandrosterone sulfotransferase (DHEA-ST), which catalyzes
      sulfonation of dehydroepiandrosterone (DHEA) to form biologically inactive DHEA
      S. A total of 162 cases including normal liver (n=31), chronic hepatitis (n=41),
      liver cirrhosis (n = 21), hepatocellular carcinoma (n = 47), cholangiocellular
      carcinoma (n = 22) and fetal liver (n = 4) were examined by immunohistochemistry.
      Both enzymes were expressed in the hepatocytes around portal area and central
      vein in normal liver. Immunopositive area for DHEA-ST was significantly larger in
      chronic hepatitis than in normal liver, but that of 17beta-HSD type 2 in chronic
      hepatitis was not different from normal liver. There were no significant
      differences in the immunopositive area for both enzymes between liver cirrhosis
      and normal liver. In hepatocellular carcinoma, immunoreactivity for both enzymes
      were categorized into Group A, or low positive group, and Group B, or high
      positive group. The latter tended to be poorly differentiated carcinoma. In
      cholangiocellular carcinoma, immunopositive areas of both enzymes were
      significantly smaller than those of normal liver. These findings indicate that
      the amount of expression of the enzymes involved in metabolism and/or clearance
      of sex steroids per hepatocyte did not decrease in liver cirrhosis. Therefore,
      sex steroids' abnormalities may be due to the decreased quantity of hepatocytes
      associated with liver cirrhosis. In hepatocellular carcinoma, some poorly
      differentiated cases were associated with increased expression of 17beta-HSD type
      2 but its biological significance needs to be determined by further studies.

PMID- 11228045
TI  - Changes in plasma concentrations of inhibin A and inhibin B throughout sexual
      maturation in the male chimpanzee.
AB  - Profiles of circulating plasma inhibin A and inhibin B during sexual maturation
      in male chimpanzees were investigated by using two-site enzyme-linked immunoassay
      (ELISA). Plasma concentrations of testosterone and pituitary gonadotropins were
      also measured. Concentrations of inhibin B, testosterone, luteinizing hormone
      (LH) and prolactin increased with age throughout prepuberty to adulthood, whereas
      inhibin A level was low and there were no age-related changes in concentrations
      of either inhibin A and follicle-stimulating hormone (FSH). Inhibin B showed an
      inverse correlation with FSH in adult (7 years or order) but not in immature (6
      years or younger) male chimpanzees. There was no correlation between plasma
      levels of FSH and testosterone throughout the period of sexual maturation.
      However, testosterone levels were positively correlated with inhibin B levels.
      These results suggest that circulating inhibin B is involved in the regulation of
      FSH secretion after puberty in adult male chimpanzees, and also that circulating
      inhibin B is an important form of inhibin as a marker of Sertoli cell function in
      adult male chimpanzees.

PMID- 11228046
TI  - Characterization of genes encoding the pancreatic beta-cell ATP-sensitive K+
      channel in persistent hyperinsulinemic hypoglycemia of infancy in Japanese
      patients.
AB  - Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a genetic disorder
      characterized by unregulated insulin secretion and profound hypoglycemia.
      Recently, mutations of SUR1 and Kir6.2, which constitute the pancreatic beta-cell
      ATP-sensitive potassium (K(ATP)) channel, have been shown to be associated with
      familial PHHI in certain ethnic groups. In the present study, we examined
      clinical symptoms, therapy, and variations in the SUR1 and Kir6.2 genes in eight
      Japanese patients with PHHI. Four patients were being treated with
      pharmacological agents and the other four had required pancreatectomy to
      normalize glucose levels. There was no difference in timing of the onset of
      hypoglycemia between the groups. There also was no difference in severity between
      the two groups, as assessed by blood glucose levels, plasma insulin levels, and
      birth weight. However, all of the pancreatectomized patients and none of the
      medically treated group had presented with seizures. By genetic screening, we
      found eleven nucleotide substitutions in the SUR1 gene, three of which result in
      amino acid changes, and three nucleotide substitutions in the Kir6.2 gene, two of
      which result in amino acid changes, but all of these genetic variants had been
      previously reported in normal subjects. These results indicate that the mechanism
      of hypoglycemia in these patients is different from those previously reported in
      PHHI patients, giving further support to the view that PHHI is a heterogeneous
      disorder.

PMID- 11228047
TI  - Estrogen secreting adrenal adenocarcinoma in an 18-month-old boy: aromatase
      activity, protein expression, mRNA and utilization of gonadal type promoter.
AB  - We examined clinical, endocrinological and molecular biological aspects of an
      estrogen-secreting adrenal carcinoma in an 18-month-old male to clarify the
      pathogenesis of this condition. An 18-month-old boy was referred for evaluation
      of progressive bilateral gynecomastia and appearance of pubic hair. The patient
      had elevated plasma estradiol (349 pg/ml) and testosterone (260 ng/dl) levels
      that completely suppressed FSH and LH levels, and was subsequently diagnosed with
      an adrenal tumor on the right side. After removal of a 300-g adenocarcinoma,
      gynecomastia regressed and essentially normal hormone levels were restored.
      Aromatase activity in the tumor tissue determined by the 3H-water method was 71.0
      104.4 pmol/min/mg protein. High levels of aromatase protein and mRNA in the tumor
      tissue were also demonstrated, while neither aromatase activity nor protein was
      detected in normal adrenal glands. To investigate the regulation of aromatase
      expression in the adrenal carcinoma, we examined the usage of alternate promoters
      responsible for aromatase gene transcription. In the present case, the amounts of
      aromatase mRNA utilizing gonadal types of exon 1c (1.3) and 1d (II) were
      significantly higher than those that using other exon 1s. This result suggested
      that the utilization of a gonadal-type exon 1 might be involved in the over
      production of aromatase in estrogen-secreting adrenal carcinoma.

PMID- 11228048
TI  - Hyperthyroidism in a patient with TSH-producing pituitary adenoma coexisting with
      thyroid papillary adenocarcinoma.
AB  - A 27-year-old woman who presented with a left thyroid nodule was found to have
      hyperthyroidism caused by a syndrome of inappropriate secretion of TSH. The
      levels of free T3, free T4 and TSH were 9.50 pg/mL, 4.05 ng/dL and 2.16
      microU/mL, respectively. Magnetic resonance imaging of the head revealed a
      pituitary macroadenoma. The TSH response to TRH stimulation was normal and
      responses of other anterior pituitary hormones to stimulation tests were also
      normally preserved. Administration of octreotide with iodine successfully
      reversed hyperthyroidism prior to total resection of pituitary adenoma, which was
      followed by hemithyroidectomy of the left thyroid five months later.
      Histologically, the resected pituitary adenoma was a TSH-producing adenoma (TSH
      oma) and the thyroid nodule was a papillary adenocarcinoma. Serum TSH diminished
      to undetectable levels immediately following pituitary adenomectomy but gradually
      normalized over nine months. Coexistence of a TSH-oma with thyroid cancer is very
      rare and only two similar cases have previously been documented. This combination
      raises the possibility that TSH may be involved in tumorigenesis in the thyroid
      gland.

PMID- 11228049
TI  - Insulin-like growth factor-I-dependent signal transduction pathways leading to
      the induction of cell growth and differentiation of human neuroblastoma cell line
      SH-SY5Y: the roles of MAP kinase pathway and PI 3-kinase pathway.
AB  - IGF-I regulates cell growth, differentiation, and survival in many cultured nerve
      cell lines. The present study was undertaken in the human neuroblastoma cell
      line, SH-SY5Y, to elucidate whether there are differences in the IGF-dependent
      signal transduction pathways that stimulate proliferation compared to those that
      induce differentiation. Quiescent SH-SY5Y cells were treated with IGF-I in the
      presence or absence of PD98059 (an inhibitor of MEK, a MAP kinase kinase) or
      LY294002 (an inhibitor of PI 3-kinase). Cell growth was assessed by measuring
      [3H]thymidine incorporation into DNA and cell number. Cell differentiation was
      assessed by measuring mRNA levels of NPY and neurite outgrowth. IGF-I both
      induced cell proliferation and differentiation. It stimulated tyrosine
      phosphorylation of the type I IGF receptor (IGF-IR) beta-subunit, IRS-I, IRS-2,
      and Shc, and these changes were associated with activation of Erk and Akt.
      PD98059 inhibited activation of Erk and LY294002 repressed activation of Akt in
      response to IGF-I, but did not affect tyrosine phosphorylation of the IGF-IR, IRS
      1, IRS-2, or Shc. Each PD98059 and LY294002 inhibited IGF-I-dependent cell
      proliferation in a concentration-dependent manner. In contrast, each of these
      inhibitors only partially depressed NPY gene expression induced by IGF-I and
      slightly inhibited IGF-I-mediated neurite outgrowth; however, when both PD98059
      and LY294002 were present, IGF-I-dependent NPY gene expression and neurite
      outgrowth were abolished completely. These results suggest that in these nerve
      cells, 1) the IGF-I signals through the MAP kinase pathway and PI-3 kinase
      pathway are independently essential to induce IGF-I-dependent growth, and 2)
      alternate activation of the MAP kinase pathway and PI 3-kinase pathway is
      sufficient for the cells to undergo IGF-I-dependent differentiation.

PMID- 11228050
TI  - HLA-associated cellular response to GAD in type 2 diabetes with antibodies to
      GAD.
AB  - Proliferative response of peripheral blood mononuclear cells (PBMC) to glutamic
      acid decarboxylase (GAD), which has been reported in patients with type 1
      diabetes, was measured in type 2 diabetes, especially in patients with antibodies
      to GAD initially diagnosed as having type 2 diabetes (anti-GAD+ type 2 diabetes).
      We studied 12 patients with type 1 diabetes, 22 with anti-GAD+ type 2 diabetes,
      31 with type 2 diabetes who were negative for anti-GAD (anti-GAD+ type 2
      diabetes), and 30 healthy control subjects for cellular responses in vitro to
      GAD. The mean stimulation index (SI) in response to GAD was significantly higher
      in type 1 diabetes than in anti-GAD+ type 2 diabetes or healthy controls (1.47+/
      0.35 vs. 1.11+/-0.35, P<0.05, and 1.06+/-0.07, P<0.05, respectively). The mean

PMID- 11228051
TI  - Chronic sulfonylurea treatment and hyperglycemia aggravate disproportionately
      elevated plasma proinsulin levels in patients with type 2 diabetes.
AB  - It is established that disproportionately elevated plasma proinsulin levels occur
      in patients with Type 2 diabetes. In the present study, multivariate analysis was
      performed to determine what factors contributed to the disproportionately
      elevated plasma proinsulin levels in Japanese patients with Type 2 diabetes
      (n=276). Results from univariate analysis showed that both fasting proinsulin/C
      peptide ratio and proinsulin/IRI ratio were approximately 2-fold higher in
      patients with Type 2 diabetes than those in healthy nondiabetic subjects (n=45).
      In patients with Type 2 diabetes, both proinsulin/C-peptide ratio and
      proinsulin/IRI ratio were significantly positively correlated with fasting plasma
      glucose level (FPG) and HbA1c. Neither proinsulin/C-peptide ratio nor
      proinsulin/IRI ratio was significantly correlated with BMI. Sulfonylurea-treated
      subjects had a significant elevation in both proinsulin/C-peptide ratio and
      proinsulin/IRI ratio compared with diet-treated subjects, whereas nonsulfonylurea
      hypoglycemic agent-treated subjects did not. Multivariate analysis confirmed that
      sulfonylurea treatment and FPG were significant determinants of both fasting
      proinsulin/C-peptide ratio (P=0.006 and P=0.030, respectively) and proinsulin/IRI
      ratio (P=0.003 and P=0.016, respectively) in patients with Type 2 diabetes. These
      results imply that disproportionate hyperproinsulinemia may reflect an excessive
      overwork of beta cells under chronic sulfonylurea treatment as well as
      hyperglycemia.

PMID- 11228052
TI  - Reconstituted basement membrane induces glandular-like morphogenesis but no
      difference in ACTH synthesis of anterior pituitary cells.
AB  - Basement membrane, a thin extracellular matrix, promotes tissue integrity and
      differentiated phenotype. This study was performed in order to investigate the
      effect of basement membrane components on adrenocorticotropin (ACTH) synthesis
      and to observe its relationship with cell morphology. Rat anterior pituitary
      cells were cultured on plastic culture plate coated with either Matrigel or poly
      D-lysine. Phase-contrast microscopy and scanning electron microscopy showed that
      cells cultured on Matrigel appeared as a three-dimensional glandular-like cell
      aggregate, while those cultured on plastic showed a flat, confluent monolayer.
      Reverse-transcription polymerase chain reaction (RT-PCR) and Northern blot
      analysis revealed that ACTH synthesis in the Matrigel culture was not
      significantly different from that in the plastic culture. Our results suggest
      that the relationship between the morphological changes caused by cell-substrate
      interaction and pituitary hormone synthesis does not exist in all pituitary cell
      types and that other factors associated with cell-substrate interaction influence
      the hormone synthesis of some pituitary cells.

PMID- 11228053
TI  - Japanese familial patients with male-limited precocious puberty.
AB  - Familial male-limited precocious puberty (FMPP) is a rare disease caused by
      constitutively activating mutations in the luteinizing hormone receptor (LH-R)
      gene. In the present study, we analyzed the LH-R gene in members of a Japanese
      FMPP family. Two males of the family were affected and had a heterozygous M398T
      mutation; one patient developed pubertal signs as early as 2 years of age, and
      the other at 6 years of age. Both patients had elevated serum testosterone levels
      and prepubertal gonadotropin secretions. The father of the latter patient carried
      the M398T mutation, but lacked history of precocious puberty. Thus, phenotypic
      differences were observed in the three males with the same LH-R mutation
      belonging to the same family. In summary, we have described a Japanese family
      with FMPP.

PMID- 11228054
TI  - Transient thyrotoxicosis and hypothyroidism following administration of the GnRH
      agonist leuprolide acetate.
AB  - A 45-year-old women with chronic idiopathic thrombocytopenic purpura was given
      monthly injections of the GnRH agonist leuprolide acetate for the treatment of
      uterine leiomyoma. Two weeks after the fifth injection, she showed mild symptoms
      of thyrotoxicosis. At that time, serum thyroxin (T4) and triiodothyronine (T3)
      levels were elevated whereas TSH level was suppressed. Anti-thyroglobulin (anti
      Tg) and anti-thyroid peroxidase (anti-TPO) antibodies were positive, whereas TSH
      binding inhibitory immunoglobulin (TBII) was undetectable. Two months later,
      serum T4 and T3 levels spontaneously decreased below the normal ranges. Five
      months after the onset of the disease, they returned to normal without any
      treatment. Anti-TPO and anti-Tg antibodies gradually decreased during the
      clinical course. Thus, the present case was indicated to be an instance wherein
      silent thyroiditis developed after leuprolide acetate administration. This is the
      first report to demonstrate the association of thyroid disorder with leuprolide
      injection.

PMID- 11228055
TI  - A case of obesity, diabetes and hypertension treated with very low calorie diet
      (VLCD) followed by successful pregnancy with intrauterine insemination (IUI).
AB  - The patient was a 32-year-old obese woman with a history of type 2 diabetes and
      hypertension for 6 years. Although she was treated with antihypertensive agents
      and intensive insulin therapy, her hyperglycemia was difficult to control. She
      wanted to have a baby but pregnancy was not recommended because her diabetes was
      under poor control and the use of antihypertensive medication. To achieve good
      control of obesity, diabetes and hypertension, she was admitted to our clinical
      department for weight reduction using very low calorie diet (VLCD). During VLCD
      she had a 19.8 kg reduction in body weight and her blood glucose and blood
      pressure were in good control without the use of drugs. Five months later, she
      became pregnant after the fourth trial of intrauterine insemination (IUI) and
      gave birth to a female baby under insulin therapy. This is the first report that
      showed the usefulness of VLCD for prepregnant control of glucose metabolism and
      blood pressure in an obese hypertensive patient with type 2 diabetes mellitus.

PMID- 11228056
TI  - Recurrence of Cushing's disease after long-term remission due to pituitary
      apoplexy.
AB  - We encountered a case with long-term remission of Cushing's disease due to
      pituitary apoplexy. The apoplexy of pituitary adenoma secreting
      adrenocorticotropin hormone was diagnosed by successive and timely magnetic
      resonance imaging when the symptoms of the patient were not yet severe and
      anterior pituitary dysfunction was only a transient reduction of growth hormone
      secretion. Seven years after the first episode of pituitary apoplexy,
      hypercorticism recurred, and pituitary magnetic resonance imaging showed a
      regrowth of the pituitary adenoma. A spontaneous remission of Cushing's disease
      without significant visual, neurologic or hormonal defects seems to be a much
      more common phenomenon than has been previously suggested. Cases with relapse
      after spontaneous remission of Cushing's disease are rare and the duration of
      remission in previous reports was within 5 years. We observed such a patient with
      a 7 year-remission caused by pituitary apoplexy. We consider that a careful long
      term follow-up is required for patients with Cushing's disease whose remission
      was due to pituitary apoplexy.

PMID- 11228057
TI  - Dehydroepiandrosterone suppresses elevated hepatic glucose-6-phosphatase mRNA
      level in C57BL/KsJ-db/db mice: comparison with troglitazone.
AB  - Dehydroepiandrosterone (DHEA) is known to improve hyperglycemia of diabetic
      C57BL/KsJ-db/db mice that are obese and insulin resistant. In a previous study,
      we reported that DHEA as well as troglitazone suppresses the elevated hepatic
      gluconeogenic enzymes, glucose-6-phosphatase (G6Pase) and fructose-1,6
      bisphosphatase (FBPase) activities in C57BL/KsJ-db/db mice. In the present study,
      we evaluated the changes in mRNA of G6Pase and FBPase in db/db mice. Despite
      hyperinsulinemia, the G6Pase mRNA level of db/db mice was elevated as compared to
      their heterozygote littermate db/+m mice. In contrast, the FBPase mRNA level was
      not elevated in db/db mice. Administration of DHEA for two weeks significantly
      decreased the blood glucose level and the elevated G6Pase mRNA level in db/db
      mice. No significant changes were seen in the FBPase mRNA level after the
      administration of DHEA. Administration of troglitazone also decreased the blood
      glucose and G6Pase mRNA level in db/db mice although no changes were seen in the
      FBPase mRNA level. These results suggest that the elevation of G6Pase mRNA is
      important in elucidating the cause of insulin resistance, and that the G6Pase
      gene is at least one target for the hypoglycemic effects of DHEA as an insulin
      sensitizing agent in db/db mice.

PMID- 11228058
TI  - Mitochondrial gene transfer ribonucleic acid (tRNA)Leu(UUR) 3243 is not a common
      cause of gestational diabetes mellitus in Spanish women.

PMID- 11228059
TI  - Production and physiological function of granulocyte colony-stimulating factor in
      non-pregnant human endometrial stromal cells.
AB  - Effects of granulocyte colony-stimulating factor (G-CSF) on proliferation and
      differentiation of normal human endometrial stromal cells were investigated in an
      in vitro decidualization culture of stromal cells. Unstimulated stromal cells
      secreted little prolactin and G-CSF, whereas 8-Br-cAMP-stimulated stromal cells
      secreted higher levels. There was no relationship, however, between the levels of
      prolactin and G-CSF secreted from the stimulated cells. Detectable levels of
      prolactin secretion were not found in two of six stromal cell cultures stimulated
      with 8-Br-cAMP; however, these two culture supernatants contained high
      concentrations of G-CSF. Co-stimulation of the stromal cells with 8-Br-cAMP and G
      CSF enhanced prolactin secretion from the stimulated cells in a G-CSF
      concentration-dependent manner without any change in viable cell numbers.
      However, G-CSF did not affect prolactin secretion or viable cell numbers of 8-Br
      cAMP-stimulated decidualized cells. These results indicate that G-CSF enhances
      cAMP-mediated decidualization of human endometrial stromal cells in an autocrine
      or paracrine fashion.

PMID- 11228060
TI  - Estradiol suppression and recovery during leuprolide acetate treatment in women
      as determined weekly by an ultrasensitive recombinant cell bioassay.
AB  - We studied the time frame of suppression and recovery of estradiol after
      injection with leuprolide acetate utilizing an ultrasensitive recombinant cell
      bioassay for estradiol in eight normal premenopausal women. Previous studies have
      shown suppression of gonadotropins and estradiol at 4 weeks after the depot
      injection, but no studies have shown the weekly time course of estradiol
      suppression or recovery. Four women received one 3.75 mg i.m. injection of
      leuprolide acetate and four received two 3.75 mg doses of leuprolide acetate 4
      weeks apart. Estradiol, luteinizing hormone (LH) and follicle-stimulating hormone
      (FSH) levels were measured weekly for 8 to 12 weeks. Estradiol was significantly
      suppressed to 26.6 +/- 19.3% of baseline values by week 3 after the initial dose
      of leuprolide acetate and suppressed to 2.7 +/- 3.1% of baseline values by week 4
      (p < 0.01 versus baseline). The actual values were less than 14.7 pmol/l (4
      pg/ml) in all women by week 4. Estradiol remained suppressed for 8 weeks after
      one dose of leuprolide acetate and remained suppressed for 6 weeks after a second
      dose administered 4 weeks later. LH and FSH followed a similar pattern, but only
      remained suppressed for 7 weeks after one dose of leuprolide acetate and for 6
      weeks after two doses. Estradiol levels at baseline were significantly correlated
      with body mass index (BMI). We also studied one postmenopausal woman. Her
      baseline estradiol levels were 10.3 pmol/l (2.8 pg/ml) and were suppressed to 3.9
      pmol/l (1.1 pg/ml) by 2 weeks after leuprolide acetate. In conclusion, estradiol
      was suppressed to postmenopausal levels by the end of the first month of
      treatment with leuprolide acetate, as determined by an ultrasensitive bioassay.
      Higher doses would need to be tested to determine whether greater suppression can
      be achieved. The hypothalamic-pituitary-gonadal axis begins to recover 7 weeks
      after one dose and 6 weeks after a second dose of leuprolide acetate. This
      confirms the adequacy of 4-week dosing to maintain estradiol and gonadotropin
      suppression in adult women treated with leuprolide acetate, but raises the
      question whether less frequent dosing may be possible in some situations, or
      whether higher doses may be needed in some situations for an even greater degree
      of estradiol suppression.

PMID- 11228061
TI  - Hormonal and clinical effects of GnRH agonist alone, or in combination with a
      combined oral contraceptive or flutamide in women with severe hirsutism.
AB  - The objective of this prospective randomized study was to evaluate and compare
      the hormonal and clinical effects of long-acting gonadotropin-releasing hormone
      (GnRH) agonist and a combination of GnRH agonist with combined oral contraceptive
      (COC) or flutamide in women with polycystic ovary syndrome (PCOS). Thirty-five
      hirsute women with PCOS, ranging in age from 19-27 years, were randomly divided
      into three groups: group A treated with GnRH agonist (n = 12), group B (n = 12)
      treated with GnRH agonist plus COC and group C (n = 11) treated with GnRH agonist
      plus flutamide for 6 months. Before, at the end and 6 months after the end of
      treatment, blood samples were drawn from all women (in early follicular phase in
      those with menstrual cycles) to measure ovarian and adrenal androgens,
      gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH),
      estradiol and estrone plasma levels. The results showed that all three protocols
      had good therapeutic efficacy. A significant reduction in hirsutism was observed
      in all patients after 6 months of therapy, the Ferriman-Gallwey scores dropping
      to 9 +/- 3 in group A, 10 +/- 4 in group B and 11 +/- 5 in group C. Six months
      after the end of therapy, the hirsutism score continued to be significantly
      reduced in all groups. After 6 months of therapy, a reduction in plasma levels of
      LH, FSH, estrone, estradiol, testosterone, free testosterone, androstenedione and
      dehydroepiandrosterone sulfate (DHEAS) was observed in all groups although this
      was more pronounced in group B and group C. These therapies may be the basis of
      future treatments that quickly reduce hirsutism and remove its causes by reducing
      the secretion of ovarian and adrenal androgens and by blocking androgen
      receptors.

PMID- 11228062
TI  - Polycystic ovary syndrome: a new ultrasonographic and color Doppler pattern.
AB  - The aim of this study was to evaluate whether patients with partial bilateral
      polycystic ovaries show different ovarian and uterine blood flow to those with
      complete bilateral polycystic ovaries, and to investigate whether there is a
      correlation between ultrasonographic and hormonal parameters. Fifteen patients
      with partial polycystic ovaries and eighteen patients with complete bilateral
      polycystic ovaries underwent clinical, biochemical, gray-scale and color Doppler
      ultrasonographic evaluation. Hormonal (luteinizing hormone (LH), follicle
      stimulating hormone (FSH), LH/FSH concentration ratio, estradiol, prolactin,
      androstenedione, testosterone), clinical (body mass index, Ferriman-Gallwey
      score), ultrasonographic (ovarian volume, number and distribution of subcapsular
      follicles, stromal score) and Doppler (uterine artery and intraparenchymal
      vessels pulsatility index, ovarian stromal vascularization) parameters were
      evaluated, in the early follicular phase (cycle day 3-5) in oligomenorrheic
      patients, or at random in amenorrheic patients. Significantly higher
      androstenedione plasma levels and LH/FSH concentration ratios were observed in
      complete bilateral polycystic ovaries. In partial polycystic ovaries, gray-scale
      and color Doppler ultrasonography showed different features in affected and
      unaffected areas of the ovary, similar to polycystic and normal ovary appearance
      respectively. In conclusion, PCOS does not predetermine a single ultrasonographic
      or Doppler pattern.

PMID- 11228063
TI  - A comparative study of the acceptability and effect of goserelin and nafarelin on
      endometriosis.
AB  - The effects of goserelin and nafarelin were compared in a prospective,
      randomized, open, parallel study of 6 months' treatment of 252 women with
      symptomatic, laparoscopically proven endometriosis. Twenty-eight departments of
      obstetrics and gynecology in Sweden, Norway, Denmark and Finland were included.
      Evaluations were made every 3 months for quantification of pain, bleeding and
      adverse events and convenience of treatment, and at 3 months after the end of
      treatment, when a control laparoscopy was performed for evaluation of changes in
      endometriotic lesion size, color and location. Thirty-nine patients withdrew and
      113 women given goserelin and 100 women given nafarelin completed the study.
      There were no statistically significant differences between the groups, either in
      adverse events or in bleeding. There were no correlations between location,
      lesion size or type of lesion, and symptom score in either group, or between
      treatments with regard to change in endometriosis score. In both groups, the
      percentage of red and black lesions was reduced while the proportion of white
      lesions increased. The pain score was significantly reduced in both groups. Local
      irritation in the nasal mucosa was reported in both groups, mostly in the
      nafarelin-treated group. The goserelin-treated group also reported local symptoms
      at the injection site. We conclude that there is no statistically significant
      difference in treatment results or side-effects between goserelin and nafarelin
      when used for the treatment of endometriosis.

PMID- 11228064
TI  - The rationale for requesting a second consecutive sperm ejaculate for assisted
      reproductive technology.
AB  - We assessed the value of requesting a second semen sample provided within 1 hour
      of the first in cases of unacceptable ejaculate quality (compared to previous
      occasions) or very poor semen characteristics. The study population consisted of
      109 males with severe oligo-terato-astenospermic (OTA) syndrome in an assisted
      reproduction program. Semen volume, sperm count and sperm motility were recorded
      in the first and second samples with a Makler Counting Chamber before sperm
      processing, and total motile sperm in the ejaculate was calculated. Differences
      in sperm parameters between the consecutive samples were determined by paired
      sample t test. In 36 cases (33%) the second sample was found to be superior in
      quality to the first and was therefore used for the fertilization process. Of the
      12/109 cases in which the first ejaculate demonstrated no motile sperm, five
      (41%) had detectable motile sperm in the second (total 0.1 x 10(6), 0.2 x 10(6),
      0.3 x 10(6), 8.4 x 10(6) and 20.8 x 10(6)). We conclude that a request for second
      ejaculate immediately after the first in males with poor semen quality or no
      detectable motile sperm can yield a better sample in a significant percentage of
      cases. Using this method, clinicians can avoid the utilization of elaborate sperm
      processing techniques and the need for unnecessary micromanipulative
      fertilization.

PMID- 11228065
TI  - Treatment versus no treatment of transient hyperprolactinemia in patients
      undergoing intracytoplasmic sperm injection programs.
AB  - The aim of our study was to investigate the effect of increased plasma prolactin
      levels on oocyte and fertilization rate in patients undergoing in vitro
      fertilization (IVF) intracytoplasmic sperm injection (ICSI) treatment. We
      identified 135 patients with transient or borderline hyperprolactinemia, measured
      in the mid and late follicular phase and in the mid-luteal phase of the cycle
      before ovarian stimulation. The patients were assigned to either the no treatment
      group (76 patients) or the treatment group (59 patients). The treated group
      underwent treatment with cabergoline or bromocriptine before ovarian stimulation,
      until there was a decrease of plasma prolactin levels, and the therapy was
      continued also during the ICSI programme. Both groups received a gonadotropin
      releasing hormone (GnRH) agonist and were subsequently stimulated with follicle
      stimulating hormone (FSH) up to the day of human chorionic gonadotropin (hCG)
      administration. The untreated group needed a significantly lower number of FSH
      ampoules than the treated group to reach the day of hCG administration (38.1 +/-
      18.2 versus 43.9 +/- 28.5; p < 0.05). No correlation was found between the two
      groups on the peak estradiol level achieved, the progesterone level at hCG
      administration and the numbers of oocytes retrieved. The number of oocytes with
      superior morphology (87.9% versus 80.4%; p < 0.05), the fertilization rate (70.8
      +/- 28.0 versus 60.8 +/- 28.5; p < 0.03), and the mean number of embryos
      transferred (3.6 +/- 1.6 versus 3.2 +/- 1.5; p < 0.05) were significantly higher
      in the patients whose hyperprolactinemia was left untreated. In conclusion, we
      found that transient hyperprolactinemia is positively associated with ICSI
      outcome, in particularly with oocyte quality and fertilization rate.

PMID- 11228066
TI  - Serum leptin concentration in cord blood: relationship to birth weight and gender
      in pregnancies complicated by pre-eclampsia.
AB  - The aim of the study was to investigate cord blood leptin concentrations and
      their relationship to birth weight and gender in term pregnancies complicated by
      pre-eclampsia. Cord blood samples were obtained from 52 women, identified as
      having pre-eclampsia, and their newborns (31 males and 21 females) immediately
      after birth. Specimens were analyzed using a human leptin 125I radioimmunoassay.
      The relationship between leptin and anthropometrics was assessed by Spearman
      correlation. Differences in cord blood leptin levels between male and female
      infants were tested with the Mann-Whitney U test. The correlation between leptin
      and gender was computed using the product-moment-biseral correlation analysis for
      continuous and dichotomous variables. The multiple logistic regression analysis
      examined influences of sex, birth length, birth weight, birth weight/birth length
      ratio, ponderal index and maternal leptin as covariates on the fetal cord leptin
      level. Fetal leptin correlated positively with birth weight, length and
      weight/length ratio, in the total group and in the male subgroup and additionally
      with ponderal index in the female subgroup. Cord blood leptin concentrations in
      female newborns were significantly higher than in male newborns (p = 0.015), and
      concentrations correlated with gender (r = -0.315; p = 0.023). Multiple logistic
      regression analysis revealed four potential independent factors influencing fetal
      cord leptin: gender, birth weight, birth weight/birth length ratio and maternal
      leptin. In conclusion, cord leptin concentrations in pregnancies complicated by
      pre-eclampsia correlate positively with birth weight and gender. Leptin
      concentrations in female newborns are higher compared to male newborns.

PMID- 11228067
TI  - Changes in sexual behavior in Bulgarian women after the menopause.
AB  - Sexual dysfunction is frequently observed in postmenopausal women but there are
      few epidemiological studies of the relationship between the menopause and sexual
      functioning. An epidemiological study of sexual function was performed among 619
      Bulgarian women aged between 40 and 58 years. Two hundred and eighty-five (46%)
      had a normal menstrual cycle (group A) and 334 (54%) were postmenopausal. Of
      these, 302 (group C) did not use hormone replacement therapy (HRT) and 32 were on
      HRT (group B). Many women feel uneasy and are unwilling to talk about their
      sexual problems even with medical professionals. This fact warranted the
      implementation of an anonymous questionnaire. There were significant differences
      in all sexual function parameters reported between groups C and A (p < 0.001), as
      well as between groups C and B (p < 0.05). These results suggest that HRT
      restores the dynamics of sexual life in postmenopausal women and brings them
      closer to those of normally menstruating middle-aged women.

PMID- 11228068
TI  - A risk factor for female fertility and pregnancy: celiac disease.
AB  - Celiac disease is a genetically-based intolerance to gluten. In the past, celiac
      disease has been considered a rare disease of infancy characterized by chronic
      diarrhea and delayed growth. Besides the overt enteropathy, there are many other
      forms which appear later in life; target organs are not limited to the gut, but
      include liver, thyroid, skin and reproductive tract. It is now recognized that
      celiac disease is a relatively frequent disorder; the overall prevalence is at
      least 1:300 in Western Europe. Celiac disease may impair the reproductive life of
      affected women, eliciting delayed puberty, infertility, amenorrhea and precocious
      menopause. Clinical and epidemiological studies show that female patients with
      celiac disease are at higher risk of spontaneous abortions, low birth weight of
      the newborn and reduced duration of lactation. No adequate studies are available
      on the rate of birth defects in the progeny of affected women; however, celiac
      disease induces malabsorption and deficiency of factors essential for
      organogenesis, e.g. iron, folic acid and vitamin K. The overall evidence suggests
      that celiac disease patients can be a group particularly susceptible to
      reproductive toxicants; however, the pathogenesis of celiac disease-related
      reproductive disorders still awaits clarification. At present, like the other
      pathologies associated with celiac disease, the possible prevention or treatment
      of reproductive effects can only be achieved through a life-long maintenance of a
      gluten-free diet.

PMID- 11228069
TI  - Paracrine/autocrine control of female reproduction.
AB  - Neuropeptides, growth factors and cytokines are expressed in reproductive organs
      and tissues, where they interact with afferent endocrine messages to modulate
      cell proliferation and differentiation, local hormone secretion and vascular
      function. These events regulate complex processes such as gonadotropin
      pulsatility, ovulation, implantation and parturition. During reproductive life, a
      number of neuropeptides produced within the hypothalamus play a modulatory role
      in the control of gonadotropin-releasing hormone (GnRH) release, hence
      characterizing a hypothalamic paracrine system. The pituitary gland is a source
      and target of inhibin-related proteins, and these typical 'gonadal' products,
      once secreted by the pituitary cells, acquire the function of paracrine
      modulators of follicle-stimulating hormone (FSH) secretion. In the ovary, the
      effect of gonadotropins is locally modulated by growth factors acting in an
      autocrine/paracrine manner, although their precise role in folliculogenesis
      remains uncertain. Numerous local factors are involved in the control of
      endometrial growth, differentiation, receptivity and menstruation. Alterations in
      the paracrine endometrial system may underlie pathological processes such as
      infertility or endometrial neoplasia. The human placenta and its related
      membranes produce cytokines, hormones and growth factors that participate in the
      control of gestational development as well as in the maternal-fetal adaptation to
      gestational diseases. There is increasing evidence that paracrine signaling plays
      a fundamental role in all spheres of female reproductive function, and future
      research will concentrate on clarifying which of these local mechanisms play a
      decisive role in both physiology and disease, thus giving rise to new therapeutic
      strategies.

PMID- 11228070
TI  - Fluid retention with oral contraceptives.

PMID- 11228071
TI  - Comments on Ross & Darke's "The nature of benzodiazepine dependence among heroin
      users".

PMID- 11228072
TI  - The myth of needle fixation.

PMID- 11228073
TI  - Time for reform: proposals for the modernization of our licensing laws.

PMID- 11228074
TI  - Per capita alcohol consumption and all-cause mortality in 14 European countries.
AB  - AIMS: (1) To estimate the relationship between per capita alcohol consumption and
      male all-cause mortality in 14 European countries. (2) To compare the estimates
      with predictions from the U-shaped curve at the aggregate level. DATA AND METHOD:
      The outcome measures comprised annual data, after 1950, on male mortality (all
      cause mortality and mortality from diseases) for the following age groups: 15+,
      15-29, 30-49, 50-69 and 70+ years. Female mortality was included as a control
      variable. Alcohol sales were used as proxy for per capita consumption. The data
      were analysed using the Box-Jenkins technique. The estimated alcohol effects were
      pooled within low-, medium- and high-consumption countries. RESULTS: For all
      cause mortality (15+), the effect estimates were significantly positive in eight
      of the 14 countries. The effect on mortality of a 1-litre increase in consumption
      tended to be stronger in low-consumption countries (3% per litre) than in medium-
      and high-consumption countries (1%). This pattern deviates from that predicted
      from the U-shaped curve. No significant impact of alcohol was found in the
      youngest age group when mortality from diseases was used as the outcome.
      CONCLUSIONS: Increases in overall consumption seem to be associated with
      increases in total mortality. Differences in drinking patterns are discussed as a
      possible explanation for the variation between country groups in alcohol effect.

PMID- 11228075
TI  - Per capita alcohol consumption and liver cirrhosis mortality in 14 European
      countries.
AB  - AIM: To estimate the effects of changes in per capita alcohol consumption on
      liver cirrhosis mortality rates in various demographic groups across 14 western
      European countries. METHOD: Yearly changes in gender- and age-specific mortality
      rates from 1950 to 1995 were analysed in relation to corresponding yearly changes
      in per capita alcohol consumption, employing the Box-Jenkins technique for time
      series analysis. Country-specific estimates were pooled into three regions:
      northern, central and southern Europe. MEASUREMENTS: Cirrhosis mortality data for
      5-year age groups were converted into gender-specific mortality rates in the age
      groups 15+, 15-44, 45-64 and 65+ and expressed as the number of deaths per
      100,000 inhabitants. Alcohol sales were used to measure aggregate consumption,
      which were calculated into consumption (litres 100% alcohol) per year per
      inhabitant over 14 years of age and weighted with a 10-year distributed lag
      model. FINDINGS: The country-specific analyses demonstrated a positive and
      statistically significant effect of changes in per capita consumption on changes
      in cirrhosis mortality in 13 countries for males and in nine countries for
      females. The strongest alcohol effect was found in northern Europe, due mainly to
      a large effect in Sweden. Moreover, when different age groups were analysed
      significant estimates were obtained in 29 of 42 cases for males and in 20 of 42
      cases for females. Most of the non-significant estimates were found in older age
      groups. CONCLUSIONS: The results suggest clearly that a change in the overall
      level of drinking as a general rule affect cirrhosis mortality in different
      drinking cultures as well as among different demographic groups. Moreover, the
      findings correspond with what is expected from the collectivity theory of
      drinking cultures.

PMID- 11228076
TI  - Alcohol consumption and overall accident mortality in 14 European countries.
AB  - AIMS: To evaluate the effects of changes in aggregate alcohol consumption on
      overall accident mortality in 14 western European countries after 1950, and to
      compare traditional beer, wine, and spirits countries with respect to the impact
      of alcohol. DESIGN, SETTING AND PARTICIPANTS: The countries were sorted into
      three groups--traditional spirits countries of northern Europe, traditional beer
      countries of central Europe and wine countries of southern Europe. Gender- and
      age-specific annual mortality rates were analysed in relation to per capita
      alcohol consumption, utilizing the Box-Jenkins technique for time series
      analysis. All series were different to remove long-term trends. The results of
      the analyses in individual countries were pooled within each group of countries
      to increase the statistical power. MEASUREMENTS: Overall accident mortality data
      for 5-year age groups were converted to gender and age specific mortality rates
      in the age groups 15-29, 30-49 and 50-69 years. Rates were age adjusted within
      groups. Data on per capita alcohol consumption were converted to consumption per
      inhabitant 15 years and older. FINDINGS: The analyses demonstrated a
      statistically significant and positive relationship between changes in aggregate
      alcohol consumption in all three groups of countries. The estimated effect
      parameter was larger in northern Europe than in central Europe, and smallest in
      southern Europe. CONCLUSION: The results are compatible with the hypothesis that
      accident mortality rates are influenced by per capita alcohol consumption in
      southern, central and northern Europe. However, alcohol appears to play a larger
      role in northern Europe than in southern Europe.

PMID- 11228077
TI  - Alcohol consumption and mortality rates from traffic accidents, accidental falls,
      and other accidents in 14 European countries.
AB  - AIMS: To evaluate the effects of changes in aggregate alcohol consumption on
      fatal motor vehicle traffic accidents, accidental falls, and other accidents in
      14 western European countries after 1950, and to compare traditional beer, wine
      and spirits countries. DESIGN, SETTING AND PARTICIPANTS: The countries were
      sorted into three groups. Gender-specific, age-adjusted annual mortality rates
      (15-69 years) were analysed in relation to per capita alcohol consumption,
      utilizing the Box-Jenkins technique for time series analysis. All series were
      different to remove long-term trends. The results of the analyses of individual
      countries were pooled within each group of countries to increase the statistical
      power. MEASUREMENTS: Overall accident mortality data for 5-year age groups were
      converted to age-adjusted mortality rates for the age group 15-69 years, using a
      European standard population. Data on per capita alcohol consumption were
      converted to consumption per inhabitant 15 years and older. FINDINGS: For male
      accidental falls, the analyses uncovered a statistically significant association
      with alcohol consumption in northern and central Europe, but not in southern
      Europe. Among females the association was insignificant in all regions. For male
      traffic accidents, significant relationships were uncovered in central and
      southern Europe, but not in northern Europe. Among females the effect was
      significant only in central Europe. For the remaining fatal accidents a
      significant relationship was found for north European males only. CONCLUSION: The
      association between aggregate alcohol consumption and rates of fatal accidents is
      mainly due to traffic accidents in central and southern Europe, and to falls and
      other accidents in northern Europe.

PMID- 11228078
TI  - Alcohol and mortality: methodological and analytical issues in aggregate
      analyses.
AB  - This supplement includes a collection of papers that aim at estimating the
      relationship between per capita alcohol consumption and various forms of
      mortality, including mortality from liver cirrhosis, accidents, suicide,
      homicide, ischaemic heart disease, and total mortality. The papers apply a
      uniform methodological protocol, and they are all based on time series data
      covering the post-war period in the present EU countries and Norway. In this
      paper we discuss various methodological and analytical issues that are common to
      these papers. We argue that analysis of time series data is the most feasible
      approach for assessing the aggregate health consequences of changes in population
      drinking. We further discuss how aggregate data may also be useful for judging
      the plausibility of individual-level relationships, particularly those prone to
      be confounded by selection effects. The aggregation of linear and curvilinear
      risk curves is treated as well as various methods for dealing with the time-lag
      problem. With regard to estimation techniques we find country specific analyses
      preferable to pooled cross-sectional/time series models since the latter
      incorporate the dubious element of geographical co-variation, and conceal
      potentially interesting variations in alcohol effects. The approach taken in the
      papers at hand is instead to pool the country specific results into three groups
      of countries that represent different drinking cultures; traditional wine
      countries of southern Europe, beer countries of central Europe and the British
      Isles and spirits countries of northern Europe. The findings of the papers
      reinforce the central tenet of the public health perspective that overall
      consumption is an important determinant of alcohol-related harm rates. However,
      there is a variation across country groups in alcohol effects, particularly those
      on violent deaths, that indicates the potential importance of drinking patterns.
      There is no support for the notion that increases in per capita consumption have
      any cardioprotective effects at the population level.

PMID- 11228079
TI  - Alcohol and suicide in 14 European countries.
AB  - AIMS: To test the hypothesis that a positive population-level relationship
      between alcohol and suicide is more likely to be found in dry drinking cultures
      (as indicated by consumption level) than in wet drinking cultures. DESIGN: Gender
      and age-specific suicide rates in 14 western European countries were analysed in
      relation to per capita alcohol consumption employing the Box-Jenkins technique
      for time series analysis. The country-specific estimates were pooled into low-,
      medium- and high-consumption countries. MEASUREMENTS: Suicide mortality data for
      5-year age groups were converted into gender- and age-specific mortality rates.
      Alcohol sales expressed as litres of 100% alcohol per year and inhabitants 15
      years and older were used as a measure of alcohol consumption. FINDINGS: A
      positive and significant relationship between per capita consumption and gender-
      and age-specific suicide rates was revealed most often in northern Europe and
      found least often in southern Europe. A stronger absolute alcohol effect for men
      was found only in northern Europe, whereas the relative alcohol effect was
      somewhat stronger for women in both northern and central Europe. Also, the
      suicide rate in younger age groups was more often significantly related to per
      capita consumption than suicide among the elder in northern and central Europe
      but not in southern Europe. CONCLUSIONS: The population-level association between
      alcohol and suicide is conditioned by cultural factors. In general, the suicide
      rate tends to be more responsive to changes in alcohol consumption in drinking
      cultures characterized by a low post-war per capita consumption compared to
      drinking cultures with higher consumption levels. The findings give support to
      the hypothesis derived from previous theoretical and empirical work, suggesting
      that suicide and alcohol is more closely connected in dry cultures than in wet
      cultures.

PMID- 11228080
TI  - Alcohol and homicide: a cross-cultural comparison of the relationship in 14
      European countries.
AB  - AIMS: To assess an empirical basis for cross-national and cross-cultural
      comparisons of four aspects of the association between alcohol consumption and
      homicide: the relative strength of the association, the fraction of homicide
      rates attributable to alcohol consumption, possible gender differences in the
      association between consumption and victim rates and possible variations in
      beverage-specific effects on homicide rates. DESIGN, SETTING AND PARTICIPANTS:
      Time series analyses on different series of annual aggregate-level data on
      alcohol sales and homicide rates for the period 1950-95 were performed for each
      individual country. Estimates were pooled across countries within three regions
      of alleged differences in drinking pattern: southern Europe, central Europe and
      northern Europe. FINDINGS: Total alcohol sales were positively and statistically
      significantly associated with homicide rates in five countries. Beer sales were
      positively and statistically significantly associated with homicide rates in four
      countries, wine sales in another two countries, and spirits sales in two
      countries. The effect of alcohol sales was stronger for male homicide rates than
      for female homicide rates, and the estimated fraction of homicides that could be
      attributed to alcohol consumption appeared to be of the same magnitude in the
      three regions. When estimates were pooled across countries, the strongest
      association between total sales and homicides was found in the northern European
      countries and the weakest, but still statistically significant, in the southern
      European countries. Pooled estimates showed that beer sales were positively and
      significantly associated with homicide rates in all three European regions,
      whereas wine sales were positively and moderately associated with homicide rates
      only in the traditional wine drinking cultures in southern Europe. CONCLUSION:
      The findings support the hypothesis that homicide rates are influenced by alcohol
      sales and more so in the northern European countries where the drinking culture
      is, to a larger extent, characterized by heavy drinking episodes. Moreover, the
      findings are suggestive of beverage-specific effects on violent behaviour being
      contingent upon characteristics of the drinking culture.

PMID- 11228081
TI  - Per capita alcohol consumption and ischaemic heart disease mortality.
AB  - AIM: To test the hypothesis that alcohol consumption is inversely related to
      ischaemic heart disease (IHD) mortality at the population level. Most individual
      level studies find a reduced risk of IHD with a moderate level of alcohol
      consumption, but it is as yet unknown whether this association also exists at the
      aggregate level. MEASUREMENTS: The study period was approximately 1950 to 1995;
      14 EU countries and Norway were included. Time series analyses on different data
      were utilized, and age-standardized IHD mortality for men and women in the age
      groups 30-44, 45-59, 60-74 and 30-74 years was measured. The effects of alcohol
      (sales per capita) were controlled for a weighted lag of per capita sales of
      cigarettes. FINDINGS: There was a random distribution of insignificant negative
      and positive alcohol effect estimates. A slight indication of a cardioprotective
      effect of alcohol among 30- to 44-year-old women in high consumption countries
      could be observed (significant for Italy). Mean alcohol effect estimates were
      nearly exactly zero (absent alcohol effect) among men and weakly positive among
      women. Because changes in cigarette consumption were often significantly and
      positively related to subsequent changes in IHD mortality, poor validity in the
      IHD time series cannot explain the unsystematic findings. Including a 6-year
      weighted lag of alcohol consumption changed the weak positive effect among women
      to an absent alcohol effect. A brief analysis of abstinence rates indicated no
      particular relationship to IHD mortality. CONCLUSION: The alleged
      cardioprotective alcohol effect is absent at the population level, and great
      caution should be taken concerning alcohol policies for cardioprotective
      purposes.

PMID- 11228082
TI  - Diagnosis of coronary artery disease with Tl-201 SPECT in patients with left
      bundle branch block: importance of alternative interpretation approaches for left
      anterior descending coronary lesions.
AB  - Left bundle branch block (LBBB) is a strong predictor of mortality in the
      presence of coronary artery disease (CAD). Noninvasive evaluation of CAD in these
      patients has some difficulties. Exercise-induced electrocardiographic ST segment
      changes are nondiagnostic, and several scintigraphic studies have reported false
      positive anteroseptal and septal perfusion defects up to 80%. The authors aimed
      to assess the diagnostic accuracy of thallium-201 (Tl-201) exercise myocardial
      single photon emission computerized tomography (SPECT) in comparison with
      coronary angiography (CAG) for detection of CAD in patients with LBBB. Seventy
      seven consecutive patients suffering from chest pain with complete and permanent
      LBBB were included in the study. All patients (40 women, 37 men, mean age = 54 +/
      7 years) were studied with Tl-201 exercise SPECT and coronary angiography. Tl
      201 exercise SPECT for diagnosis of left anterior descending (LAD) artery lesions
      was interpreted by using three different approaches: method A (conventional
      approach), method B (involvement of anterior and septal wall regardless of apical
      wall), and method C (apical approach: involvement of anterior septal and apical
      wall). Methods A and B gave a sensitivity of 100% each but a specificity of 47%
      and 56%, respectively. Although method C gave a higher value of specificity than
      that of methods A and B (98% vs 47% and 56%, respectively p < 0.05), the
      sensitivity of method C significantly decreased in respect to methods A and B
      (33% vs 100% p < 0.01). Isolated septal defects were evaluated separately.
      Isolated septal defects on exercise Tl-201 SPECT were detected in 11 patients,
      and none of them had CAD according to CAG results. Isolated septal wall
      involvement had a sensitivity of 0% and a specificity of 74%. The sensitivity and
      specificity of Tl-201 SPECT for diagnosis of CAD in the right coronary and left
      circumflex artery territories were 91% and 89%, respectively. In conclusion, the
      apical approach increased the specificity and decreased the sensitivity of the
      test. Isolated septal defects seem to have no value for diagnosis of CAD in
      patients with left bundle branch block.

PMID- 11228083
TI  - Circulating interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, and
      soluble ICAM-1 in patients with chronic stable angina and myocardial infarction.
AB  - The changes in serum concentrations of cytokines such as interleukin-1 (IL-1)
      beta, interleukin-6 (IL-6), tumor necrosis factor (TNF) alpha and a soluble
      intercellular adhesion molecule (sICAM-1) has been investigated in patients with
      stable angina and acute myocardial infarction. Thirty-four patients with stable
      angina (SA), 15 with acute myocardial infarction (AMI), and 20 subjects in the
      control (C) group were included in the study. The mean serum concentrations of
      sICAM-1, IL-1-beta, IL-6, and TNF-alpha differed significantly among the three
      groups. Serum concentrations of IL-1 beta, sICAM-1, and TNF-alpha were comparable
      in the AMI and SA groups and higher than those found in the C group (p < 0.001).
      The serum concentration of IL-6 was more than twice as high in the AMI group as
      compared to the other two groups (p < 0.001). The mean serum concentrations of IL
      1 beta, TNF-alpha, and IL-6 were comparable in the AMI and SA groups and higher
      than in the C group.

PMID- 11228084
TI  - A long-term study of policosanol in the treatment of intermittent claudication.
AB  - Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects.
      This study was undertaken to investigate the long-term effects of policosanol
      administered to patients with moderately severe intermittent claudication. The
      study consisted of a 6-week single-blind, placebo-controlled run in phase,
      followed by a 2-year double-blind, randomized treatment step. Fifty-six patients
      who met study entry criteria were randomized to receive placebo or policosanol 10
      mg twice daily. Walking distances on a treadmill (constant speed 3.2 km/h, slope
      10 degrees, temperature 25 degrees C) were assessed before and after 6, 12, 18,
      and 24 months of treatment. Both groups were similar at randomization. After 6
      months of therapy, policosanol significantly increased (p < 0.01) the initial
      claudication distance from 125.9 +/- 8.7 m to 201.1 +/- 24.8 m and the absolute
      claudication distance from 219.5 +/- 14.1 m to 380.7 +/- 50.2 m. Both variables
      remained unchanged in the placebo group (p < 0.01). These effects did not wear
      off but improved after long-term therapy, so that final values were 333.5 +/-
      28.6 m (initial claudication distance) and 648.9 +/- 54.1 m (absolute
      claudication distance); both significantly greater (p < 0.0001) than those
      obtained in the placebo group, which showed values of 137.9 +/- 21.8 m (initial
      claudication distance) and 237.7 +/- 28.1 m (absolute claudication distance),
      respectively. At study completion, 21 policosanol and 5 placebo patients attained
      increases in claudication distance values > 50% (p < 0.001). Policosanol, but not
      placebo, significantly increased the ankle/arm pressure index. In addition, from
      month 6 up to study completion, the frequency of patients reporting improvement
      of lower limb symptoms was greater in the policosanol group than in the placebo
      group. The treatment was tolerated well. There were 16 withdrawals (12 placebo, 4
      policosanol) from the study. Eight patients in the placebo group experienced a
      total of 10 serious adverse events, 8 of which were vascular events, compared
      with none in the policosanol group (p < 0.01). In addition, 3 patients in the
      policosanol group and 3 patients in the placebo group reported mild adverse
      events during the study. The present results demonstrate the long-term usefulness
      of policosanol therapy to treat patients with intermittent claudication.

PMID- 11228085
TI  - Superficial thrombophlebitis and anticardiolipin antibodies--report of
      association.
AB  - The aim of this study was to determine a possible association between recidivist
      superficial thrombophlebitis and anticardiolipin antibodies. Forty-five patients
      with two or more episodes of superficial thrombophlebitis in lower limbs (33
      women and 12 men with ages ranging from 17 to 60 years, average: 39.8) were
      studied. The control group was formed by 100 voluntary donors from the blood bank
      (83 men and 17 women, age range: 21 to 59 years, average: 35.4). Anticardiolipin
      antibody concentrations were determined by enzyme-linked immunosorbent assay
      (ELISA). For semiquantitative detection in human sera with use of QUANTA Lite ACA
      IgG/IgM--INOVA Diagnostic, Inc., and positive values were considered as 15 GPL
      units/mL and 12.5 MPL units/mL for immunoglobulin G (IgG) and IgM, respectively,
      as recommended by the test. The Odds Ratio method was chosen for statistical
      analysis with a confidence interval (CI) of 95%. In 15 patients (33.3%)
      anticardiolipin antibody positivity was detected, whereas in 12 patients (26.7%)
      it occurred as immunoglobulin M (IgM) anticardiolipin and in 3 (6.7%) as
      immunoglobulin G anticardiolipin. In the control group, positivity was found in 7
      patients (7%) for those antibodies. Furthermore, the Odds Ratio = 6.64 with CI =
      95% and values ranging from 2.48 to 17.82 (p < 0.05) were significant, as well as
      for IgM/IgG anticardiolipin proportion with Odds Ratio = 5.09, C = 95% and values
      varying from 1.33 to 19.54 (p < 0.05). The authors conclude that there is a
      correlation between the presence of anticardiolipin antibodies and recurrent
      superficial thrombophlebitis.

PMID- 11228086
TI  - Comparison between isosorbide dinitrate in aerosol and in tablets for the
      treatment of hypertensive emergencies.
AB  - Sixty patients with a hypertensive emergency (mean arterial pressure >130 mm Hg
      and evidence of target organ damage) were randomly divided into two groups of 30
      patients each. Group A received 1.25 mg of isosorbide dinitrate aerosol upon
      arrival and a second dose 15 minutes later when the mean arterial pressure
      reduction was < 15%. Group B received a single 5 mg tablet of sublingual
      isosorbide dinitrate. Electrocardiography was performed in both groups prior to
      and 30 minutes after the medication. Blood pressure was monitored for 6 hours.
      Blood pressure in Group A patients decreased in an average time of 10 minutes
      from 191 +/- 12/122.3 +/- 5 to 151.5 +/- 9.2/93 +/- 4 mm Hg, p < 0.005. Mean
      arterial pressure decreased by 22.8%: 145 +/- 7 to 112 +/- 7.5 mm Hg, p < 0.005.
      No adverse effects occurred. Five patients in Group B did not respond; in the
      rest of the group blood pressure decreased 45 minutes after receiving the
      medication from 194 +/- 8/125 +/- 5.5 to 160 +/- 11/98 +/- 6 mm Hg; p < 0.005.
      Mean arterial pressure decreased by 20.1%: 148.3 +/- 12 to 118.6 +/- 9 mm Hg, p <
      0.002; ten patients suffered headache. Three patients in Group A had a
      subepicardial lesion in the first electrocardiograph, which disappeared with the
      use of the aerosol. In Group B, electrocardiography results were normal. These
      results seem to indicate that isosorbide dinitrate aerosol is better than tablets
      for the treatment of patients with a hypertensive emergencies.

PMID- 11228087
TI  - Refractory no-reflow successfully treated with local infusion of high-dose
      adenosine and verapamil--a case report.
AB  - No-reflow is an unpredictable complication following percutaneous coronary
      intervention. No-reflow is associated with myocardial ischemia and infarction and
      increased mortality. A case of refractory no-reflow is described that was rapidly
      and successfully treated with multiple infusions of high doses of verapamil and
      adenosine applied directly at the site of no-reflow through a perfusion catheter.

PMID- 11228088
TI  - Acute myocardial infarction secondary to coronary vasospasm during withdrawal
      from industrial nitroglycerin exposure--a case report.
AB  - Industrial exposure to nitrates is known to produce acute and chronic effects on
      the cardiovascular system. A case of acute inferior myocardial infarction in a
      young, otherwise healthy, white male that occurred during the usual weekend
      withdrawal period is presented.

PMID- 11228089
TI  - Exercise-induced left bundle branch block during thallium 201 myocardial
      perfusion scintigraphy--a case report.
AB  - Exercise-induced left bundle branch block (Ex-LBBB) is a rare entity encountered
      during exercise testing. The authors present a 53-year-old woman who developed
      intermittent Ex-LBBB asymptomatically during Tl 201 myocardial perfusion
      scintigraphy. Scintigraphic findings revealed septal-anteroseptal ischemia while
      the coronary arteriogram appeared normal. False-positive septal-anteroseptal
      scintigraphic findings suggesting ischemia in patients with persistent left
      bundle branch block (LBBB) is well known, but since the LBBB in this case was
      induced by exercise testing and was spontaneously terminated at rest,
      scintigraphic findings may be attributed to microcirculatory ischemia, which
      cannot be detected angiographically, as the cause of Ex-LBBB.

PMID- 11228090
TI  - An unusual increase of blood anti-beta 2-glycoprotein-I antibody but not
      antiphospholipid antibody in cerebral ischemia--a case report.
AB  - An abnormal increase in anti-beta2-glycoprotein I antibodies (abeta2GPI) is
      capable of producing thrombosis and the vasculopathy-simulating antiphospholipid
      antibody (aPL). However, it is rarely described in cerebral ischemia without an
      association with aPL. The authors report a middle-aged man who experienced
      recurrent cerebral ischemia and diffuse cerebral stenosis without the apparent
      traditional cardiovascular risk factor. He was free of antiphospholipid/cofactor
      syndrome (APCS) and systemic lupus erythematosus (SLE). An increase of blood
      abeta2GPI was detected in serial measurements. The aPL, Venereal Disease Research
      Laboratory (VDRL) test, Coombs' test, and antinuclear factor were negative.
      Activated partial thromboplastin time was normal. This patient is a reminder to
      consider abeta2GPI in an unexplained recurrent cerebral thrombosis and cerebral
      artery stenosis even when the typical clinical manifestation or laboratory data
      of APCS is absent.

PMID- 11228091
TI  - Successful resuscitation of patient with massive coronary air embolism occluding
      two vessels during coronary angiography--a case report.
AB  - Massive coronary air embolism is usually disastrous although successful
      resuscitation has been reported previously. To what extent a patient with
      coronary air embolism can be resuscitated is not known. The authors report a rare
      case of massive air embolism to the left coronary arteries and successful
      resuscitation by vigilantly maintaining an effective driving force to dissipate
      the air lock.

PMID- 11228092
TI  - The genesis of atherosclerosis and risk factors: a review.
AB  - Atherosclerosis constitutes the most common medical and surgical problem. This
      can be manifested clinically as stroke, coronary artery disease, or peripheral
      vascular disease. In the present review the microscopic appearance of the normal
      arterial wall, the definition of atherosclerosis and the five theories of
      atherogenesis are described. These are: the lipid theory, the hemodynamic theory,
      the fibrin incrustation theory, the nonspecific mesenchymal hypothesis and the
      response to injury hypothesis. Based on the above theories the sequence of events
      in atherogenesis is analyzed. The classification of the atherosclerotic lesions
      according to Stary (types I-VI) and their characteristics appear in a table. The
      epidemiology and the role of the following risk factors are presented in detail:
      age, sex, lipid abnormalities, cigarette smoking, hypertension, diabetes
      mellitus, physical inactivity, alcohol consumption, obesity, and hemostatic
      factors. In addition, less common genetically determined associations like
      homocystinuria, Tangier disease, Hutchinson-Gilford syndrome (progeria), Werner's
      syndrome, radiation induced atherosclerosis and the implications of Chlamydia
      pneumoniae on the arterial wall are discussed.

PMID- 11228093
TI  - Robotically assisted video-enhanced-endoscopic coronary artery bypass graft
      surgery.
AB  - Since 1988, through fierce industry-driven competition and patients' preference
      for minimally invasive procedures, widely diffused through the media,
      laparoscopic cholecystectomy was universally adopted and rapidly became the "gold
      standard" for symptomatic cholelithiasis. Robotically assisted video enhanced
      endoscopic coronary artery bypass surgery (RAVE-CABG) will most likely follow
      suit with its similar developmental processes for symptomatic coronary artery
      disease. Since 1998, there are currently two surgical robotic systems that have
      been used in a clinical setting for endoscopic coronary artery bypass (ECABG):
      the da Vinci and the ZEUS system. Although each has separate learning curves to
      overcome, as with any new technology, both offer the promise to contribute in the
      interests of reduced hospital days, earlier return to normal activity, less pain,
      better cosmesis, and the rethinking of surgical dogma such as wide exposure.

PMID- 11228094
TI  - Insulin-like growth factor-1 protects H9c2 cardiac myoblasts from oxidative
      stress-induced apoptosis via phosphatidylinositol 3-kinase and extracellular
      signal-regulated kinase pathways.
AB  - Oxidative stress plays a critical role in cardiac injuries during
      ischemia/reperfusion. Insulin-like growth factor-1 (IGF-1) promotes cell survival
      in a number of cell types, but the effect of IGF-1 on the oxidative stress has
      not been elucidated in cardiac muscle cells. Therefore, we examined the role of
      IGF-1 signaling pathway in cell survival against H2O2-induced apoptosis in H9c2
      cardiac myoblasts. H2O2 treatment induced apoptosis in H9c2 cells, and
      pretreatment of cells with IGF-1 suppressed apoptotic cell death. The
      antiapoptotic effect of IGF-1 was blocked by LY294002 (an inhibitor of
      phosphatidylinositol 3-kinase) and by PD98059 (an inhibitor of extracellular
      signal-regulated kinase (ERK)). The protective effect of IGF-1 was also blocked
      by rapamycin (an inhibitor of p70 S6 kinase). Furthermore, H9c2 cells stably
      transfected with constitutively active PI 3-kinase (H9c2-p110*) and Akt (H9c2-Gag
      Akt) constructs were more resistant to H2O2 cytotoxicity than control cells.
      Although H2O2 activates both p38 mitogen-activated protein kinase (MAPK) and c
      Jun N-terminal kinase (JNK), IGF-1 inhibited only JNK activation. Activated PI 3
      kinase (H9c2-p110*) and pretreatment of cells with IGF-1 down-regulated Bax
      protein levels compared to control cells. Taken together, our results suggest
      that IGF-1 transmits a survival signal against oxidative stress-induced apoptosis
      in H9c2 cells via PI 3-kinase and ERK-dependent pathways and the protective
      effect of IGF-1 is associated with the inhibition of JNK activation and Bax
      expression.

PMID- 11228095
TI  - Determination of bufalin-like immunoreactivity in serum of humans and rats by
      time-resolved fluoroimmunoassay for using a monoclonal antibody.
AB  - The existence of a mammalian natriuretic substance or endogenous digitalis-like
      factor, which inhibits Na+,K+-ATPase and thereby regulates body fluid volume, has
      been speculated for a long time but has yet to be defined. We established in the
      present study a simple and highly sensitive procedure to measure bufalin, a
      constituent of toad venom preparation and a specific inhibitor of Na+,K+-ATPase
      by time-resolved fluoroimmunoassay (TR-FIA) and using a monoclonal antibody. The
      antibody was specific to bufalin and resembled bufadienolides but showed no cross
      reactivity with digitoxin and ouabain. A bufalin-like immunoreactivity was
      detectable in serum of humans and rats by the proposed TR-FIA. The levels of
      bufalin-like immunoreactivity in serum of healthy volunteers were significantly
      correlated with their systolic blood pressure. Moreover, bufalin-like
      immunoreactivity in serum of Dahl-S rats increased in parallel with a period of
      high-salt diet. These results suggest that increased bufalin-like
      immunoreactivity may be associated with certain types of hypertension.

PMID- 11228096
TI  - Characterization of late-pregnant rat uterine contraction via the contractility
      ratio in vitro significance of alpha1-adrenoceptors.
AB  - The aim of this study was to characterize the ability of late-pregnant (days 15
      22) rat uterine tissue rings to contract in response to electric field
      stimulation in vitro. For this purpose, maximum rhythmic contractions were
      elicited by optimum choice of the period time and the pulse width, the two main
      parameters of electric field stimulation. In parallel, the plasma 17beta
      estradiol and progesterone levels were determined. It was found that the
      contractility ratio, i.e. the quotient of the optimum pulse width and the period
      time, is a good parameter with which to express the contractility. The larger the
      contractility ratio, the better the ability to contract. Evaluation of the area
      under the curve did not furnish information relating to the contractility in this
      method. A very close correlation was observed between the contractility ratio and
      the quotient of the 17beta-estradiol and progesterone levels on different days,
      demonstrating that the in vitro ability characterized by the contractility ratio
      is in keeping with the physiological regularity. There was also a very close
      correlation between the contractility ratio and the quotient of the alpha1- and
      beta-adrenergic receptors, suggesting the main role of the numbers of alpha1
      receptor in pregnant uterine contractility. It is believed that this is the first
      in vitro model to give a numerical measure concerning the ontogeny of uterine
      contractility in late pregnancy.

PMID- 11228097
TI  - Purine nucleotide catabolism in rat liver: labelling of uric acid and allantoin
      after treatment with oxonic acid and allopurinol.
AB  - In our previous experiments on rat liver we found that 15' after intraperitoneal
      administration of 14C-formate the specific radioactivity of allantoin was always
      higher than that of uric acid. The present experiments have been carried out to
      interpret this unexpected result, which was only observed in liver and we
      studied: a) the incorporation of 14C-glycine into uric acid and allantoin; b) the
      effects of two competitive inhibitors of xanthine oxidase and uricase, oxonic
      acid and allopurinol respectively, on levels of uric acid and allantoin in liver
      and on their specific radioactivity after administration of labelled precursor.
      The results suggested: a) that under normal conditions, the formation of
      allantoin is so fast that it exceedes export from liver to serum, and thus the
      radioactivity of labelled precursors accumulates in allantoin; b) that when
      allopurinol or oxonic acid are administered, the rate of export exceeds that of
      allantoin formation and the incorporation of radioactivity into allantoin is
      lower; c) that not all the data, however, could be interpreted on this basis, but
      seems to require the existence of different pools of uric acid, which are
      transformed separately into allantoin.

PMID- 11228098
TI  - Peripheral neural system involvement in hypoalgesic effect of electromagnetic
      millimeter waves.
AB  - In a series of blind experiments, using the cold water tail-flick test (cTFT) as
      a quantitative indicator of pain, the hypoalgesic effect of a single exposure of
      mice to low power electromagnetic millimeter waves (MW) was studied. The MW
      exposure characteristics were: frequency = 61.22 GHz; incident power density = 15
      mW/cm2; and duration = 15 min. MW treatment was applied to the glabrous skin of
      the footpad. Exposure of an intact murine paw to the MW resulted in a
      statistically significant hypoalgesia as measured in the cTFT. These mice were
      able to resist cold noxious stimulation in the cTFF more than two times longer
      than animals from the sham-exposed group. A unilateral sciatic nerve transection
      was used to deafferent the area of exposure in animals from one of the
      experimental groups. This surgery, conducted six days before the MW treatment,
      completely abolished the hypoalgesic effect of the exposure to MW. The results
      obtained support the conclusion that the MW-skin nerve endings interaction is the
      essential step in the initiation of biological effects caused by MW. Based on our
      past and present results we recommend that in order to obtain a maximum
      therapeutic effect, densely innervated skin areas (head, hands) need to be used
      preferentially for exposure to MW in clinical practice.

PMID- 11228099
TI  - Cytotoxicity of azadirachtin A in human glioblastoma cell lines.
AB  - The neem toxin azadirachtin A exhibits selective toxicity on insects. Despite its
      well-proven efficacy, the mode of action of this toxin remains obscure. The
      toxicity on vertebrate cells compared to insect cells is also not well
      characterized. We have cultivated six human glioblastoma cell lines G-28, G-112,
      G-60 (TP53 mutant) and G-44, G-62, G-120 (TP53 wild-type) in the presence of 28
      microM of azadirachtin. This toxin concentration was chosen because it represents
      the 25 to 50% lethal dose in the glioma cells. Toxicity was measured in terms of
      cell proliferation (binucleation index), formation of micronuclei and cell
      survival. In the TP53 mutant cell lines, azadirachtin reduced the proportion of
      dividing cells and induced formation of micronuclei. Except for G-44 which showed
      a decrease in binucleation index, proliferation in the TP53 wild-type cell lines
      was unaffected by azadirachtin. In the TP53 wild-type cell lines, the decrease in
      micronuclei frequency is attributed to fewer cells entering mitosis to produce
      micronuclei. This is also apparent from the low surviving fractions. Cell
      survival was suppressed by 25-69% in all cell lines. The reduction of cell
      survival is a clear indication that azadirachtin affects reproductive integrity
      and cell division. The induction of micronuclei reflects DNA damage. Similar
      studies on damage induction in insect cell lines could elucidate the processes
      which precede the antifeedant and antimoulting effects of azadirachtin and other
      neem toxins in insects.

PMID- 11228100
TI  - Angiogenesis extent and expression of matrix metalloproteinase-2 and -9 correlate
      with progression in human neuroblastoma.
AB  - In human tumors changes in angiogenesis and expression of extracellular matrix
      degrading enzymes occur simultaneously during invasion and metastasis. Tissues
      from 20 biopsies of human neuroblastoma (NB) were investigated
      immunohistochemically by using an antibody against factor VIII to determine their
      microvessel number, and by in situ hybridisation to determine the expression of
      mRNA of the matrix metalloproteinase-2 (MMP-2) and MMP-9. The extent of
      angiogenesis and the expression of the MMP-2 and MMP-9 mRNA were upregulated in
      advancing stages. These in situ data suggest that angiogenesis and degradation of
      extracellular matrix occur simultaneously with NB tumor progression.

PMID- 11228101
TI  - Angiotensin II increases neurogenic nitric oxide metabolism in mesenteric
      arteries from hypertensive rats.
AB  - We investigated, in mesenteric arteries from hypertensive rats (SHR), the
      possible changes in neurogenic nitric oxide (NO) release produced by angiotensin
      II (AII), and the possible mechanisms involved in this process. In
      deendothelialized segments the NO synthase inhibitor N(G)-nitro-L-arginine (L
      NAME, 10 microM) increased the contractions caused by electrical field
      stimulation (EFS, 200 mA, 0.3 ms, 1-16 Hz, for 30 s). AII (0.1 nM) enhanced the
      response to EFS, which was unmodified by the subsequent addition of L-NAME. The
      AII antagonist receptor saralasine (0.1 microM) prevented the effect of AII, and
      the subsequent addition of L-NAME restored the contractile response. SOD (25
      u/ml) decreased the reponse to EFS and the subsequent addition of L-NAME
      increased this response. AII did not modify the decrease in EFS response induced
      by SOD, and the addition of L-NAME increased the response. None of these drugs
      altered the response to exogenous noradrenaline (NA) or basal tone except SOD,
      which increased the basal tone, an effect blocked by phentolamine (1 microM). In
      arteries pre-incubated with [3H]-NA, AII did not modify the tritium efflux evoked
      by EFS, which was diminished by SOD. AII did not alter basal tritium efflux while
      SOD significantly increased it. These results suggest that EFS of SHR mesenteric
      arteries releases neurogenic NO, the metabolism of which is increased in the
      presence of AII by the generation of superoxide anions.

PMID- 11228102
TI  - Preventive effect of platelet-activating factor antagonist, Y-24180, against
      cyclosporine-induced acute nephrotoxicity.
AB  - To evaluate the effect of Y-24180, a potent and long-acting antagonist to
      platelet-activating factor (PAF) receptors, on cyclosporine A (CsA)-induced acute
      renal failure, the influence of its pretreatment on the CsA-induced alterations
      in renal hemodynamics was examined in male Wistar rats under anesthesia. CsA
      decreased the clearances of inulin and p-aminohippuric acid (PAH) in a dose
      dependent manner. Y-24180 (3 mg/kg, i.v.) tended to attenuate the CsA-induced
      reduction in inulin clearance. Y-24180 (0.3 and 3 mg/kg) significantly prevented
      the reductions in PAH clearance and the increase in calculated renal vascular
      resistance (RVR) in a dose-dependent manner. Serum endothelin-1 (Et)
      concentration in the CsA-treated group was higher than that in the vehicle
      treated group. Y-24180 did not influence such the elevated Et concentration.
      Serum thromboxane B2 (TxB2) concentration did not increase by treatment with CsA.
      A significant correlation was observed between RVR and Et, but not TxB2
      concentration. The present study showed that a PAF receptor antagonist, Y-24180,
      has the preventive effect against CsA-induced acute renal failure, which
      indicates that PAF may partly be involved in the mechanism of renal
      vasoconstriction induced by CsA. The present findings also support the idea that
      Et contributes to the CsA-induced acute nephrotoxicity.

PMID- 11228103
TI  - Alpha1A- and alpha1B-adrenoceptors are the major subtypes in human saphenous
      vein.
AB  - In this study we analyzed the different alpha1-adrenoceptor (AR) subtypes present
      in human saphenous vein (HSV) using reverse transcription polymerase chain
      reaction (RT-PCR), DNA-DNA hybridization analysis and functional affinities for
      alpha-AR antagonists. DNA-DNA hybridization analysis of RT-PCR amplification
      products confirmed the presence of alpha1A- and alpha1B-ARs, and low levels of
      alpha1D-AR in HSV. The functional results showed: (1) prazosin, the selective
      alpha1-AR antagonist, phentolamine, the alpha1- and alpha2-ARs antagonist, WB
      4101 and 5-MU, the selective alpha1A-AR subtype antagonists were potent,
      competitive antagonists of noradrenaline (NA)-induced contraction (pA2 values of
      11.03, 8.06, 9.02 and 8.34, respectively). (2) Alpha1-AR-induced contraction was
      sensitive to the alkylating effects of CEC (the alpha1B and alpha1D-AR subtypes
      antagonist) and (3) The selective alpha1D-AR subtype antagonist BMY displayed low
      affinity (pA2 values of 6.44). This indicates that the contractile response of
      the HSV to alpha1-AR-induced is predominantly mediated by both alpha1A and
      alpha1B-AR subtypes. This was also supported by the good relationship between pA2
      values from the present study and reported binding affinities (pKi) values of
      various alpha1-AR subtype antagonists with cloned human alpha1A- and alpha1B-AR
      subtypes (r=0.89 and r=0.98, respectively), but not the alpha1D-AR subtype
      (r=0.67). Our results indicate that alpha1A- and alpha1B-ARs are the main
      functional and expressed receptor subtypes in HSV.

PMID- 11228104
TI  - In vivo anti-inflammatory activity of saponins from Bupleurum rotundifolium.
AB  - Seven oleanane-type triterpene saponins were isolated from the methanolic extract
      of the aerial parts of Bupleurum rotundifolium. They were identified on the basis
      of their spectral data as 3-O-[alpha-L-rhamnopyranosyl (1-->2)-beta-D
      glucopyranosyl (1-->2)-beta-D-glucopyranosyl]-28-O-[beta-D-glucopyranosyl (1-->2)
      beta-D-glucopyranosyl] echinocystic acid (saponin 1), 3-O-[alpha-L
      rhamnopyranosyl (1-->2)-beta-D-glucopyranosyl (1-->2)-beta-D-fucopyranosyl] 11
      methoxy-primulagenin A (saponin 2), rotundioside E (saponin 3), rotundioside F
      (saponin 4), 3beta-sulfate, 28-O-[beta-D-glucopyranosyl (1-->6)-beta-D
      glucopyranosyl (1-->2)-beta-D-glucopyranosyl (1-->2)-beta-D-glucopyranosyl] ester
      of primulagenin A (saponin 5), rotundioside C (saponin 6) and 3-O-[alpha-L
      rhamnopyranosyl (1-->2)-beta-D-glucopyranosyl (1-->2)-beta-D-fucopyranosyl] 11
      methoxy-16beta,21alpha,28-trihydroxyolean-12-ene (saponin 7). All these saponins
      proved to be effective against TPA-induced ear edema in mice. Their ID50 were
      determined to be 248, 288, 128, 99 and 297 nmol/ear for saponin 1, 2, 3, 4 and 6,
      respectively. Saponins 3 and 6 were also active on a TPA multiple-dose model of
      skin chronic inflammation.

PMID- 11228105
TI  - Induction of apoptosis by green tea catechins in human prostate cancer DU145
      cells.
AB  - Green tea catechins (GTCs) including (-)-epigallocatechin-3-gallate (EGCG), (-)
      epigallocatechin (EGC), (-)-epicatechin-3-gallate (ECG) and (-)-epicatechin (EC)
      were shown to suppress cell growth and induce apoptosis in various cell systems
      in addition to their chemo-preventive effect. In this study, except EC which was
      inactive, green tea extract (TE) and other 3 GTCs were found to suppress the
      growth and induce apoptosis in human prostate cancer DU145 cells largely through
      an increase in reactive oxygen species formation and mitochondrial
      depolarization. The conclusion was supported by the fact that the profiles for
      different GTCs in growth suppression, apoptosis induction, ROS formation and
      mitochondrial depolarization are in a similar order, i.e. ECG > EGCG > EGC > EC.
      Although the molecular mechanisms are still not clear, apoptosis induced by GTCs
      is not related to the members of BCL-2 family as EGCG did not alter the
      expression of BCL-2, BCL-X(L) and BAD in DU145 cells.

PMID- 11228106
TI  - Microbicides 2000 conference. Welcoming remarks. The global need for
      microbicides.

PMID- 11228107
TI  - Microbicides 2000 conference. Welcoming remarks. The role of the Office of AIDS
      Research, NIH, USA.

PMID- 11228108
TI  - Microbicides 2000 conference. Welcoming remarks. Microbicides: global
      opportunities.

PMID- 11228109
TI  - Knowledge-base, evidence and evaluation in public health.

PMID- 11228110
TI  - Relation between health problems and sickness absence: gender and age differences
      -a comparison of low-back pain, psychiatric disorders, and injuries.
AB  - Women have higher long-term sickness absence rates than men, and higher rates of
      most health problems. The rates vary with type of problem and diagnosis. The
      objectives were to examine whether equal proportions of women and men had
      sickness absence when they had a given health problem, and if disparities were
      diagnosis specific. Prevalence of low-back pain, psychiatric disorders, and
      injuries was assessed in random samples of two populations in Norway. Prevalence
      of long-term sickness absence for the same diagnostic categories was estimated
      for the same time period (1990). For injuries, the prevalence ratios between a
      health problem and a sickness absence were equal for women and men. For
      psychiatric health problems, there were 1.7 more women than men behind each
      sickness absence. Low-back pain showed an intermediate gender ratio of 1.3,
      indicating that also for this condition women tended to have less sickness
      absence. Musculoskeletal and psychiatric health problems (fluctuating, chronic)
      may result in more gender-biased, subjective, and random assessment of work
      ability than injuries (acute health problem).

PMID- 11228111
TI  - Can women's network activities lead to improved health?
AB  - The aim of our study was to focus on women's networks in the Swedish county of
      Jamtland, and to analyse the relationship between network activities and the
      perceived health among the network participants, as well as participation in the
      community among its residents. Questionnaires were distributed to all 68 women's
      networks and 60 responded. The results show that the network activities correlate
      with an improved perception of health, as well as with increased participation in
      the community among the residents. The more support, influence, self-reliance and
      trust in the future experienced by the networks through their work, the better
      the health among the participants in the network. The greater the self-reliance,
      trust in the future, amount of network-related unpaid work and new jobs, the
      better the participation among the community residents. Despite its limitations,
      our study suggests that women's networks could have an important role in health
      promotion within the framework of the new public health. The network model, with
      its bottom-up strategy, could be useful in public health, provided that
      networking is not used to fill a gap when there are cuts in the public sector.

PMID- 11228112
TI  - Total cholesterol and HDL-cholesterol in relation to socioeconomic status in a
      sample of 11,645 Greek adults: the EPIC study in Greece. European Prospective
      Investigation into Nutrition and Cancer.
AB  - OBJECTIVE: To examine the relationship between educational level, a powerful
      indicator of socioeconomic status in Greece, total cholesterol and HDL
      cholesterol in a large sample of Greek adults. METHODS: The study sample
      consisted of 11,645 subjects, 4,398 men and 7,247 women, aged 23-86 years, who
      voluntarily participated in the Greek component of the EPIC study during 1994-98.
      Educational attainment was divided into low, medium, and high. Linear regression
      analyses were performed, in men and women separately, using total and HDL
      cholesterol as dependent variables and educational level as independent, while
      controlling for age. RESULTS: Total blood cholesterol values are inversely
      associated with educational level in both genders, a pattern contrasting with
      that found 20 years ago. The association is more prominent among women. HDL
      cholesterol values are inversely associated with educational level in men,
      whereas the association is less consistent in women.

PMID- 11228113
TI  - Effects of the WHO 1985 criteria and the proposed new diagnostic criteria on the
      prevalence of diabetes in an elderly population.
AB  - Population data suggest that a fasting blood glucose level of > or = 6.1 mmol/l
      corresponds best to a two-hour blood glucose level of > or = 11.1 mmol/l, which
      is associated with an increased risk of developing microvascular complications.
      The proposed new criteria, and the WHO 1985 criteria for diabetes, were applied
      in an elderly population, which underwent a two-hour oral glucose tolerance test.
      The prevalence of diabetes was higher when the proposed new criteria were used
      than when the old criteria were used. In calculating the prevalence of diabetes,
      the fasting blood glucose > or = 6.1 mmol/l corresponded better to the
      combination of fasting and/or two-hour values than did fasting blood glucose > or
      = 6.7 mmol/l. The prevalence obtained by using either of these fasting values
      alone or in combination with two-hour values corresponded poorly to that obtained
      by using mere two-hour blood glucose values.

PMID- 11228114
TI  - Over-the-counter codeine use in Iceland: the impact of increased access.
AB  - BACKGROUND: The objective of this study was to test the assumption that
      liberalizing community pharmacy ownership in Iceland would lead to increased
      irrational use of over-the-counter pain relievers containing codeine. METHODS:
      Based on this assumption we built and tested a model using an interrupted time
      series design that contrasts the monthly sales data for over-the-counter pain
      relievers containing codeine before and after the legislation took effect.
      RESULTS: The total use of over-the-counter pain relievers containing codeine as
      well as those containing paracetamol and codeine has risen steadily throughout
      the period under study. The interrupted time series did not show a substantial
      effect from the legislative change on the use of all over-the-counter codeine
      pain relievers, paracetemol with codeine, and aspirin with codeine combinations.
      CONCLUSION: The assumption that increased access leads to irrational use of over
      the-counter medicines is not substantiated in the case of over-the-counter pain
      relievers containing codeine.

PMID- 11228115
TI  - Alcohol habits in a suburban male cohort.
AB  - OBJECTIVE: Using data from a prospective birth-to-maturity project, the study
      presents normally occurring variations in alcohol involvement of alcohol-related
      problems among a representative cohort of Swedish males in young middle age, born
      in a Swedish metropolitan area (n = 106). METHODS: Description and classification
      were based on an analysis of self-reported information (collected at about 36
      years of age) about frequency and quantity of alcohol consumption (four-week
      timeline), self-reported alcohol-related symptoms, and registry data. RESULTS:
      According to a broad, operationally defined classification of "harmful drinking"
      (at least three alcohol-related symptoms, including alcohol-related crimes), 43
      subjects (41%) had experienced a substantial drinking problem during their
      lifetime, to an extent that might warrant labels such as "alcoholism" or
      "hazardous drinking". About one-third of these misusers were currently using
      other drugs. Of the 106 subjects, 80 (75%) reported having had at least one
      alcohol-related symptom or problem at some time during their life. Taking various
      life events into account, including sociomedical circumstances and heavy
      consumption at 18 and 25 years, 23 subjects (22%) were classified as having a
      lifetime prevalence of alcohol abuse/dependence according to DSM-III criteria.
      CONCLUSION: Problem drinking was largely unknown to the healthcare system and
      only a few subjects had received treatment. The results are discussed in the
      light of data from other national and international epidemiological surveys.

PMID- 11228116
TI  - Determinants of psychosomatic complaints in Swedish schoolchildren aged seven to
      twelve years.
AB  - OBJECTIVE: The aim of this study was to investigate determinants of psychosomatic
      complaints (PSC) in children. The model assumes that variables are working on
      three levels: the proximal level (the child), the intermediate level (the
      family), and the distal level (the society). METHODS: Data were obtained from a
      large cross-sectional survey on children's health and well-being in the Nordic
      countries. A questionnaire was sent to the parents of a representative sample of
      1,163 Swedish children aged seven to 12 years. The analysis included a
      multivariate analysis using the LISREL program. RESULTS: The best predictors of
      PSC were the mother's health, the child's mental stability, contacts with peers,
      and long-term illness/disability. There were many other important relationships,
      which act via factors, such as school satisfaction, social competence,
      activities, the parents' sense of coherence, and family economy. CONCLUSION: PSC
      in children should be seen in the context of all three levels.

PMID- 11228117
TI  - Mortality in elderly men with low psychosocial coping resources using anxiolytic
      hypnotic drugs.
AB  - OBJECTIVE: Insufficient coping with stress may lead to increased susceptibility
      for disease and death. Use of anxiolytic-hypnotic drugs has been suggested as a
      coping strategy, and some opinions have proposed their use as preventive
      medication. The aim of this study was to estimate if use of anxiolytic-hypnotic
      drugs counters the increased mortality observed in individuals lacking other
      coping strategies such as emotional support and social participation. METHODS: A
      population based cohort study with 10-year (1982/83-1993) survival analysis was
      performed in 491 men born in 1914, living in the Swedish city of Malmo. RESULTS:
      Compared with men with a high level of psychosocial coping resources who did not
      use anxiolytic-hypnotic drugs, men with a low level of psychosocial coping
      resources had a higher risk of death irrespective whether they used anxiolytic
      hypnotic drugs, RR = 1.7 (95% CI 1.1-2.6) or not RR = 1.8 (95%: 1.3-2.5).
      CONCLUSION: Anxiolytic-hypnotic drugs do not seem to counter increased mortality
      in elderly men with low psychosocial coping resources.

PMID- 11228118
TI  - Learning and knowledge-production for public health: a review of approaches to
      evidence-based public health.
AB  - Public health needs to be evidence-based if it is to be done correctly, which
      means that learning and knowledge-production for public health must be
      comprehensive and include knowledge from four different domains: distribution of
      health, determinants or causal web, consequences, and intervention methods.
      Specification of development trends in cardiovascular prevention points at four
      generations of preventive programs; these include a clinical, a
      bioepidemiological, a socioepidemiological, and an environmental and policy
      oriented generation. Generations differ in focus and strategy, in knowledge base-
      the art of making an impact--and evaluation. Comprehensive public health programs
      often comprise components from different generations, leading to the need for an
      expanded model for research and evaluation. There is an urgent need for learning
      and knowledge-production using both quantitative and qualitative approaches for
      developing the evidence base for public health action. In addition,
      epidemiological knowledge is necessary for making appropriate priorities.

PMID- 11228119
TI  - Health and evolution.
AB  - Darwinian medicine may shed new light on the notion of health and many current
      health problems. In this paper, health, as an ability to realize one's own
      welfare, is compared with health as an ability--either being developed or
      actually present--to perform a reproductive function of one's species. It is
      argued that knowledge about the conditions for health in the latter sense may
      enhance our efforts to promote health in the former sense.

PMID- 11228120
TI  - Variations and stability in drinking patterns in a cohort of Swedish males.
AB  - OBJECTIVE: Information on drinking patterns may make an important contribution to
      our understanding of the risks and consequences of alcohol consumption. The
      objective of the present study is to describe variations and stability of
      patterns of alcohol use at both the aggregate and the individual levels. METHODS:
      The reported alcohol consumption was recorded of a normal, representative birth
      cohort of Swedish male (n = 122) subjects followed from the age of 18 years to
      early middle age and more extensively scrutinized at the age of 36, using a 28
      day time-line follow-back technique. RESULTS: In young middle age a high
      proportion of total consumption occurred on Fridays and Saturdays (about 60%). In
      addition, it was possible to classify "standard drinkers", "sporadic binge
      drinkers", and "frequent drinkers" as separate clusters. CONCLUSION: While binge
      drinking was more stable than frequency of drinking from the age of 18 to the age
      of 36, frequent drinking showed the highest short-term stability at the age of 36
      years.

PMID- 11228121
TI  - Antibiotics, animals, and people--again!

PMID- 11228122
TI  - Graduate education.     Student survey highlights mismatch of training, goals.

PMID- 11228124
TI  - Astronomy.    Weird new exoplanets leave theory behind.

PMID- 11228123
TI  - Endangered species.    Cloned gaur a short-lived success.

PMID- 11228125
TI  - Evolutionary genetics.    Horses domesticated multiple times.

PMID- 11228126
TI  - Ecology.    How rain pulses drive biome growth.

PMID- 11228127
TI  - Astrophysics.    Microwave telescope data ring true.

PMID- 11228129
TI  - Taiwan.    Political spat delays funding for academy.

PMID- 11228128
TI  - Space station.    U.S. module to offer long-term lab space.

PMID- 11228131
TI  - Scientific community.    Preemptive strike sought to discredit book before it was
      published.

PMID- 11228130
TI  - Scientific community.    Anthropological warfare.

PMID- 11228132
TI  - American Geophysical Union.    Geophysicists probe the solar system's cold spots.

PMID- 11228133
TI  - Ecology.    Arctic life, on thin ice.

PMID- 11228134
TI  - Pacifichem 2000:    Pacific chemists throw switches, strike at disease.

PMID- 11228136
TI  - Present and future control of malaria.

PMID- 11228135
TI  - Canine assistants for conservationists.

PMID- 11228137
TI  - Present and future control of malaria.

PMID- 11228138
TI  - On the origins of photosynthesis.

PMID- 11228139
TI  - Environment.     The future of the Brazilian Amazon.

PMID- 11228140
TI  - Behavioral ecology.     Dividing up the kids.

PMID- 11228141
TI  - Nanomaterials.     Stretching the mold.

PMID- 11228142
TI  - Planetary science. The nightside of Venus.

PMID- 11228143
TI  - Immunology.     Giving inhibitory receptors a boost.

PMID- 11228144
TI  - Insulators and boundaries: versatile regulatory elements in the eukaryotic    
      genome.

PMID- 11228145
TI  - Crystal structure of an initiation factor bound to the 30S ribosomal subunit.
AB  - Initiation of translation at the correct position on messenger   RNA is essential
      for accurate protein synthesis. In prokaryotes,   this process requires three
      initiation factors: IF1, IF2, and IF3.   Here we report the crystal structure of
      a complex of IF1 and the   30S ribosomal subunit. Binding of IF1 occludes the
      ribosomal   A site and flips out the functionally important bases A1492 and  
      A1493 from helix 44 of 16S RNA, burying them in pockets in   IF1. The binding of
      IF1 causes long-range changes in the   conformation of H44 and leads to movement
      of the domains of   30S with respect to each other. The structure explains how  
      localized changes at the ribosomal A site lead to global   alterations in the
      conformation of the 30S subunit.

PMID- 11228147
TI  - 'Send me all of your reagents and ideas. We want to work on the same
      experiments'. By Caveman.

PMID- 11228146
TI  - Room-temperature ferromagnetism in transparent transition metal-doped    
      titanium dioxide.
AB  - Dilute magnetic semiconductors and wide gap oxide semiconductors are appealing
      materials for magnetooptical devices. From a combinatorial screening approach
      looking at the solid solubility of transition metals in titanium dioxides and of
      their magnetic properties, we report on the observation of transparent
      ferromagnetism in cobalt-doped anatase thin films with theconcentration of cobalt
      between 0 and 8%. Magnetic microscopy images   reveal a magnetic domain structure
      in the films, indicating the existence of   ferromagnetic long-range ordering.
      The materials remain ferromagnetic   above room temperature with a magnetic
      moment of 0.32 Bohr magnetons   per cobalt atom. The film is conductive and
      exhibits a positive   magnetoresistance of 60% at 2 kelvin.

PMID- 11228148
TI  - Diversity in phagocytic signalling.

PMID- 11228149
TI  - Phosphoinositides in membrane traffic at the synapse.
AB  - Inositol phospholipids represent a minor fraction of membrane phospholipids; yet
      they play important regulatory functions in signaling pathways and membrane
      traffic. The phosphorylated inositol ring can act either as a precursor for
      soluble intracellular messengers or as a binding site for cytosolic or membrane
      proteins. Hence, phosphorylation-dephosphorylation of phosphoinositides
      represents a mechanism for regulation of recruitment to the membrane of coat
      proteins, cytoskeletal scaffolds or signaling complexes and for the regulation of
      membrane proteins. Recent work suggests that phosphoinositide metabolism has an
      important role in membrane traffic at the synapse. PtdIns(4,5)P2 generation is
      implicated in the secretion of at least a subset of neurotransmitters.
      Furthermore, PtdIns(4,5)P2 plays a role in the nucleation of clathrin coats and
      of an actin-based cytoskeletal scaffold at endocytic zones of synapses, and
      PtdIns(4,5)P2 dephosphorylation accompanies the release of newly formed vesicles
      from these interactions. Thus, the reversible phosphorylation of inositol
      phospholipids may be one of the mechanisms governing the timing and vectorial
      progression of synaptic vesicle membranes during their exocytic-endocytic cycle.

PMID- 11228150
TI  - Illuminating the secretory pathway: when do we need vesicles?
AB  - Recent studies using GFP-tagged markers and time-lapse microscopy have allowed
      direct visualisation of membrane traffic in the secretory pathway in living
      mammalian cells. This work shows that larger membrane structures, 300-500 nm in
      size, are the vehicles responsible for long distance, microtubule-dependent ER-to
      Golgi and trans-Golgi to plasma membrane transport of secretory markers. At least
      two retrograde transport pathways from the Golgi to the ER exist, both of which
      are proposed to involve a further class of long, tubular membrane carrier that
      forms from the Golgi and fuses with the ER. Together, this has challenged
      established transport models, raising the question of whether larger pleiomorphic
      structures, rather than small 60-80 nm transport vesicles, mediate long-range
      transport between the ER and Golgi and between the Golgi and plasma membrane.

PMID- 11228151
TI  - Phagocytosis and the actin cytoskeleton.
AB  - The process of engulfing a foreign particle - phagocytosis - is of fundamental
      importance for a wide diversity of organisms. From simple unicellular organisms
      that use phagocytosis to obtain their next meal, to complex metazoans in which
      phagocytic cells represent an essential branch of the immune system, evolution
      has armed cells with a fantastic repertoire of molecules that serve to bring
      about this complex event. Regardless of the organism or specific molecules
      concerned, however, all phagocytic processes are driven by a finely controlled
      rearrangement of the actin cytoskeleton. A variety of signals can converge to
      locally reorganise the actin cytoskeleton at a phagosome, and there are
      significant similarities and differences between different organisms and between
      different engulfment processes within the same organism. Recent advances have
      demonstrated the complexity of phagocytic signalling, such as the involvement of
      phosphoinostide lipids and multicomponent signalling complexes in transducing
      signals from phagocytic receptors to the cytoskeleton. Similarly, a wide
      diversity of 'effector molecules' are now implicated in actin-remodelling
      downstream of these receptors.

PMID- 11228152
TI  - Paranemin and the organization of desmin filament networks.
AB  - De novo expression of vimentin, GFAP or peripherin leads to the assembly of an
      extended intermediate filament network in intermediate filament-free SW13/cl.2
      cells. Desmin, in contrast, does not form extended filament networks in either
      SW13/cl.2 or intermediate filament-free mouse fibroblasts. Rather, desmin formed
      short thickened filamentous structures and prominent spot-like cytoplasmic
      aggregates that were composed of densely packed 9-11 nm diameter filaments.
      Analysis of stably transfected cell lines indicates that the inability of desmin
      to form extended networks is not due to a difference in the level of transgene
      expression. Nestin, paranemin and synemin are large intermediate filament
      proteins that coassemble with desmin in muscle cells. Although each of these
      large intermediate filament proteins colocalized with desmin when coexpressed in
      SW-13 cells, expression of paranemin, but not synemin or nestin, led to the
      formation of an extended desmin network. A similar rescue of desmin network
      organization was observed when desmin was coexpressed with vimentin, which
      coassembles with desmin, or with keratins, which formed a distinct filament
      network. These studies demonstrate that desmin filaments differ in their
      organizational properties from the other vimentin-like intermediate filament
      proteins and appear to depend upon coassembly with paranemin, at least when they
      are expressed in non-muscle cells, in order to form an extended filament network.

PMID- 11228153
TI  - Rab27a enables myosin Va-dependent melanosome capture by recruiting the myosin to
      the organelle.
AB  - The peripheral accumulation of melanosomes characteristic of wild-type mouse
      melanocytes is driven by a cooperative process involving long-range,
      bidirectional, microtubule-dependent movements coupled to capture and local
      movement in the actin-rich periphery by myosin Va, the product of the dilute
      locus. Genetic evidence suggests that Rab27a, the product of the ashen locus,
      functions with myosin Va in this process. Here we show that ashen melanocytes,
      like dilute melanocytes, exhibit normal dendritic morphology and melanosome
      biogenesis, an abnormal accumulation of end-stage melanosomes in the cell center,
      and rapid, bidirectional, microtubule-dependent melanosome movements between the
      cell center and the periphery. This phenotype suggests that ashen melanocytes,
      like dilute melanocytes, are defective in peripheral melanosome capture.
      Consistent with this, introduction into ashen melanocytes of cDNAs encoding wild
      type and GTP-bound versions of Rab27a restores the peripheral accumulation of
      melanosomes in a microtubule-dependent manner. Conversely, introduction into wild
      type melanocytes of the GDP-bound version of Rab27a generates an ashen/dilute
      phenotype. Rab27a colocalizes with end-stage melanosomes in wild-type cells, and
      is most concentrated in melanosome-rich dendritic tips, where it also colocalizes
      with myosin Va. Finally, neither endogenous myosin Va nor an expressed, GFP
      tagged, myosin Va tail domain fusion protein colocalize with melanosomes in ashen
      melanocytes, in contrast to that seen previously in wild-type cells. These
      results argue that Rab27a serves to enable the myosinVa-dependent capture of
      melanosomes delivered to the periphery by bidirectional, microtubule-dependent
      transport, and that it does so by recruiting the myosin to the melanosome
      surface. We suggest that Rab27a, in its GTP-bound and melanosome-associated form,
      predominates in the periphery, and that it is this form that recruits the myosin,
      enabling capture. These results argue that Rab27a serves as a myosin Va
      'receptor', and add to the growing evidence that Rab GTPases regulate vesicle
      motors as well as SNARE pairing.

PMID- 11228154
TI  - The NITY motif of the beta-chain cytoplasmic domain is involved in stimulated
      internalization of the beta3 integrin A isoform.
AB  - Beta3 integrin adhesion molecules play important roles in wound repair and the
      regulation of vascular development and three beta3 integrin isoforms (beta3-A, 
      B, -C) have been described so far. Surface expression of beta3 integrins is
      dynamically regulated through internalization of beta3 integrins, however, the
      molecular mechanisms are understood incompletely. To evaluate the role of the
      cytoplasmic domain of beta3 integrins for internalization, we have generated
      single chain chimeras with variant and mutated forms of beta3 cytoplasmic
      domains. Upon transient transfection into chinese hamster ovary cells, it was
      found that the beta3-A chimera had strongly reduced cell surface expression
      compared with the corresponding beta3-B, or beta3-C fusion proteins, or the tail
      less constructs, whereas steady state levels of all chimeras were near identical.
      Studies employing cytoplasmic domain mutants showed that the NITY motif at beta3
      A 756-759 is critical for plasma membrane expression of beta3-A. Furthermore,
      delivery of beta3-A to the cell surface was specifically modulated by the
      cytoplasmic protein beta3-endonexin, a previously described intracellular
      protein. Coexpression of the native, long form of beta3-endonexin, which does not
      interact with the beta3 tail, acted as a dominant negative inhibitor of beta3-A
      internalization and enhanced steady-state surface expression of the beta3-A
      chimera. Furthermore, anti-beta3 antibody-induced internalization of the native
      beta3 integrin (alpha(IIb)beta3 was dramatically reduced for the Tyr(759)-Ala
      substitution mutant (alpha(IIb)beta3) (Y759A) and expression of the long isoform
      of beta3-endonexin substantially decreased the internalization of wild-type
      alpha(IIb)beta3. Thus, the NITY motif of the beta-chain cytoplasmic domain is
      involved in stimulated internalization of the beta3 integrin A isoform and beta3
      endonexin appears to couple the beta3-A isoform to a specific receptor-recycling
      pathway.

PMID- 11228155
TI  - Translocation and accumulation of exogeneous hepatitis B virus preS surface
      proteins in the cell nucleus.
AB  - Recurrent reports about protease-sensitive sites in the junction of the preS and
      S region of the hepatitis B virus large surface protein have raised the question
      about a possible biological role of S protein-depleted, independent preS protein
      fragments in the virus life cycle. In the present study, this question was
      addressed by exogenous introduction of fluorescence-labeled recombinant preS
      proteins into permeabilized HepG2 cells. While maltose-binding proteins (MBP)
      were evenly distributed throughout the cytoplasm, MBP-preS fusion proteins
      selectively accumulated in the nucleus. Using truncated preS proteins, the
      effective domain for this nuclear accumulation was localized around the preS2
      region. The mode of this action differs from conventional nuclear translocation
      mechanism in its energy- and mediator-independency and in that it is not
      saturated regardless of the increase of preS protein concentration. The
      biological meaning of this phenomenon has to be further studied. However, in
      regard to hepatitis B virus infection, this observation might provide a clue for
      unveiling the still poorly characterized events after initial internalization of
      the virus, which might make use of the nuclear translocation effect of the preS2
      region to facilitate the infection.

PMID- 11228156
TI  - Overexpression of the integrin-linked kinase mesenchymally transforms mammary
      epithelial cells.
AB  - Signals generated by the interaction of beta1 integrins with laminin in the
      basement membrane contribute to mammary epithelial cell morphogenesis and
      differentiation. The integrin-linked kinase (ILK) is one of the signaling
      moieties that associates with the cytoplasmic domain of beta1 integrin subunits
      with some specificity. Forced expression of a dominant negative, kinase-dead form
      of ILK subtly altered mouse mammary epithelial cell morphogenesis but it did not
      prevent differentiative milk protein expression. In contrast, forced
      overexpression of wild-type ILK strongly inhibited both morphogenesis and
      differentiation. Overexpression of wild-type ILK also caused the cells to lose
      the cell-cell adhesion molecule E-cadherin, become invasive, reorganize cortical
      actin into cytoplasmic stress fibers, and switch from an epithelial cytokeratin
      to a mesenchymal vimentin intermediate filament phenotype. Forced expression of E
      cadherin in the latter mesenchymal cells rescued epithelial cytokeratin
      expression and it partially restored the ability of the cells to differentiate
      and undergo morphogenesis. These data demonstrate that ILK, which responds to
      interactions between cells and the extracellular matrix, induces a mesenchymal
      transformation in mammary epithelial cells, at least in part, by disrupting cell
      cell junctions.

PMID- 11228157
TI  - Distinct roles for dystroglycan, beta1 integrin and perlecan in cell surface
      laminin organization.
AB  - Dystroglycan (DG) is a cell surface receptor for several extracellular matrix
      (ECM) molecules including laminins, agrin and perlecan. Recent data indicate that
      DG function is required for the formation of basement membranes in early
      development and the organization of laminin on the cell surface. Here we show
      that DG-mediated laminin clustering on mouse embryonic stem (ES) cells is a
      dynamic process in which clusters are consolidated over time into increasingly
      more complex structures. Utilizing various null-mutant ES cell lines, we define
      roles for other molecules in this process. In beta1 integrin-deficient ES cells,
      laminin-1 binds to the cell surface, but fails to organize into more
      morphologically complex structures. This result indicates that beta1 integrin
      function is required after DG function in the cell surface-mediated laminin
      assembly process. In perlecan-deficient ES cells, the formation of complex
      laminin-1 structures is defective, implicating perlecan in the laminin matrix
      assembly process. Moreover, laminin and perlecan reciprocally modulate the
      organization of the other on the cell surface. Taken together, the data support a
      model whereby DG serves as a receptor essential for the initial binding of
      laminin on the cell surface, whereas beta1 integrins and perlecan are required
      for laminin matrix assembly processes after it binds to the cell.

PMID- 11228158
TI  - Cdk5 mediates changes in morphology and promotes apoptosis of astrocytoma cells
      in response to heat shock.
AB  - The cyclin-dependent kinase member, Cdk5, is expressed in a variety of cell
      types, but neuron-specific expression of its activator, p35, is thought to limit
      its activity to neurons. Here we demonstrate that both Cdk5 and p35 are expressed
      in the human astrocytoma cell line, U373. Cdk5 and p35 are present in the
      detergent-insoluble cytoskeletal fraction of this cell line and Cdk5 localizes to
      filopodia and vinculin-rich regions of cell-matrix contact in lamellopodia. When
      exposed to a 46(o)C heat shock, U373 cells change shape, lose cell-matrix
      contacts and show increased levels of apoptosis. To test whether Cdk5 activation
      might play a role in these events, U373 cells were stably transfected with
      histidine-tagged or green fluorescent protein-tagged constructs of Cdk5 or a
      dominant negative mutation, Cdk5T33. Under normal growth conditions, growth
      characteristics of the stably transfected lines were indistinguishable from
      untransfected U373 cells and Cdk5 localization was not changed. However, when
      subjected to heat shock, cells stably transfected with Cdk5-T33 remained
      flattened, showed little loss of cell-matrix adhesion, and exhibited
      significantly lower levels of apoptosis. In contrast, cells that overexpressed
      wild-type Cdk5 showed morphological changes similar to those seen in
      untransfected U373 cells in response to heat shock and had significantly higher
      levels of apoptosis. Heat-shocked cells showed changes in p35 mobility and
      stability of the Cdk5/p35 complex consistent with endogenous Cdk5 activity.
      Together these findings suggest that endogenous Cdk5 activity may play a key role
      in regulating morphology, attachment, and apoptosis in U373 cells, and raise the
      possibility that Cdk5 may be a general regulator of cytoskeletal organization and
      cell adhesion in both neuronal and non-neuronal cells.

PMID- 11228159
TI  - Cell-cell adhesion in human fibroblasts requires calcium signaling.
AB  - In connective tissues, intercellular adhesion is essential for tissue
      morphogenesis, development and wound healing. However, the signaling mechanisms
      initiated by cell-cell adhesion in fibroblasts and that regulate it are not
      known. In this study we tested the hypothesis that intracellular calcium
      signaling is required to mediate intercellular adhesion between fibroblasts. Fura
      2 or fluo-3 labeled human fibroblasts were used to investigate calcium
      homeostasis during intercellular adhesion. After contact with suspended
      fibroblasts there was a rise in cytosolic free calcium ([Ca2+]i) and multiple
      calcium oscillations in substrate-attached cells. Antibodies against the
      extracellular but not the cytoplasmic domain of cadherin induced a similar
      calcium response, indicating that these responses were initiated by cadherin
      binding. As shown by the near-plasma membrane Ca2+ indicator (Fura-C18) and by
      confocal microscopy of fluo-3-loaded cells, [Ca2+]i transients probably
      originated at sites of cell-cell contact. Cell-cell adhesion was dependent on
      both calcium influx through membrane channels and release of Ca2+ from internal
      calcium stores, because the calcium channel inhibitor LaCl3 or pretreatment of
      cells with thapsigargin significantly inhibited (>35%) cell-cell attachment. The
      [Ca2+]i changes induced by cell-cell adhesion were temporally correlated with
      increased recruitment of intercellular junctional proteins into the cytoskeleton
      and movement of GFP-actin to sites of cell-cell contact. [Ca2+]i responses
      induced by intercellular adhesion were essential for both junctional protein
      recruitment and the establishment of strong cell-cell contacts, as loading cells
      with BAPTA/AM significantly inhibited cell-cell adhesion and recruitment of
      cadherins and beta-catenin to the actin cytoskeleton. Actin depolymerization by
      cytochalasin D dramatically reduced cell-cell adhesion and recruitment of
      cadherins and catenin to the actin cytoskeleton. These results demonstrate that
      cadherin-cadherin interaction induces [Ca2+]i transients during cell-cell
      adhesion in fibroblasts, and these calcium signals regulate cell-cell adhesion
      through remodeling of cortical actin and recruitment of cadherins and beta
      catenin into intercellular junctions.

PMID- 11228160
TI  - Involvement of CD44 in cytoskeleton rearrangement and raft reorganization in T
      cells.
AB  - T cell activation is accompanied by actin-mediated receptor clustering and
      reorganization of lipid rafts. It has been suggested that costimulatory molecules
      might be involved in these processes. We here provide evidence that engagement of
      the adhesion molecule CD44 initiates cytoskeletal rearrangement and membrane
      reorganization in T cells. Cross-linking of CD44 on a T helper line was
      accompanied by adhesion, spreading and actin bundle formation. These processes
      were energy dependent and required an intact actin and microtubule system. They
      involved the small GTPase Rac as evidenced by the absence of spreading in cells
      overexpressing a dominant negative form of Rac. The CD44 initiated reorganization
      of the cytoskeleton was associated with the recruitment of CD44 and the
      associated tyrosine phosphokinases p56(lck) and p59(fyn) into glycolipid enriched
      membrane microdomains (GEM). We interpret the data in the sense that CD44
      functions as a costimulatory molecule in T cell activation by inducing actin
      cytoskeletal rearrangements and membrane protein and lipid reorganization
      including its association with GEMs. Due to the association of CD44 with lck and
      fyn this colocalization with the TCR allows an abundant provision of these
      kinases, which are essential to initiate the TCR signaling cascade.

PMID- 11228161
TI  - Inhibition of neuronal maturation in primary hippocampal neurons from tau
      deficient mice.
AB  - Conflicting evidence supports a role for tau as an essential neuronal
      cytoskeletal protein or as a redundant protein whose function can be fulfilled by
      other microtubule-associated proteins. To investigate the function of tau in
      axonogenesis, we created tau deficient mice by disrupting the TAU gene. The
      engineered mice do not express the tau protein, appear physically normal and are
      able to reproduce. In contrast to a previously reported tau knockout mouse,
      embryonic hippocampal cultures from tau deficient mice show a significant delay
      in maturation as measured by axonal and neuritic extensions. The classic
      technique of selectively enhancing axonal growth by growth on laminin substrates
      failed to restore normal neuronal maturation of tau knockout neurons. By mating
      human TAU-gene transgenic and tau knockout mice, we reconstituted tau-deficient
      neurons with human tau proteins and restored a normal pattern of axonal growth
      and neuronal maturation. The ability of human tau proteins to rescue tau
      deficient mouse neurons confirms that tau expression affects the rate of neurite
      extension.

PMID- 11228162
TI  - Programmed cell death of keratinocytes culminates in apoptotic secretion of a
      humectant upon secretagogue action of acetylcholine.
AB  - The programmed cell death of the stratified squamous epithelial cells comprising
      human epidermis culminates in abrupt transition of viable granular keratinocytes
      (KC) into dead corneocytes sloughed by the skin. The granular cell-corneocyte
      transition is associated with a loss in volume and dry cell weight but the
      mechanism for and biological significance of this form of keratinocyte apoptosis
      remain obscure. We show that terminally differentiated KC extrude into the
      intercellular spaces of living epidermis the cytoplasmic buds containing randomly
      congregated components of the cytosol as well as filaggrin, a precursor of the
      natural moisturizing factor. The discharge of secretory product is reminiscent of
      holocrine secretion, suggesting the term 'apoptotic secretion' for this novel,
      essential step in the process of cornification. The secretory product may become
      a part of the glycocalyx (a.k.a. 'intercellular cement substance' of epidermis)
      and serve as a humectant that counterbalances the osmotic pressure imposed by the
      natural moisturizing factor located in the stratum corneum comprised by
      corneocytes. The apoptotic secretion commences upon secretagouge action of
      acetylcholine which is synthesized and released by KC. A combination of a
      cholinergic nicotinic agonist and a muscarinic antagonist which increases
      intracellular calcium levels is required to trigger the apoptotic secretion.
      Analysis of the relative amounts of cholinergic enzymes and receptors expressed
      by KC capable of secretion and the pharmacological profiles of secretion
      regulation revealed an upward concentration gradient of free acetylcholine in
      epidermis which may provide for its unopposed secretagogue action via the m1
      muscarinic and the alpha7, and alpha9 nicotinic receptor types expressed by KC at
      the latest stage of their development in the epidermis.

PMID- 11228163
TI  - A common regulatory locus affects both HNF4/HNF1alpha pathway activation and
      sensitivity to LPS-mediated apoptosis in rat hepatoma cells.
AB  - Lipopolysaccharide (LPS) has been shown to protect certain cultured mammalian
      cells from undergoing programmed cell death (apoptosis) when exposed to tumor
      necrosis factor (TNF). However, LPS has also been reported to induce apoptosis in
      cultured endothelial cells, suggesting that apoptotic response mechanisms may be
      dependent upon cell type. In order to understand the influence of tissue-specific
      gene expression on apoptosis, we compared LPS-induced apoptosis in hepatoma cells
      with dedifferentiated hepatoma variant cells that have been selected for the loss
      of the liver-enriched HNF4/HNF1alpha transcriptional activation pathway. We
      report here that while human, rat and mouse hepatoma cell lines are resistant to
      LPS-mediated cell death, the HNF4-/HNF1alpha- rat hepatoma variant cells undergo
      rapid apoptosis (as determined by morphological analysis, DNA laddering and the
      TUNEL assay) upon exposure to LPS. Genetic rescue experiments show that
      restoration of the HNF4/HNF1alpha pathway via chromosome transfer render the
      hepatoma variant cells resistant to LPS-mediated apoptosis. However, the
      introduction of HNF1alpha alone failed to alter the apoptotic phenotype,
      suggesting that the defect(s) in the hepatoma variant cells that influence
      apoptotic responses lies upstream of HNF4/HNF1alpha expression. This study
      provides for the first time direct evidence of a common regulatory locus involved
      in activation of hepatic gene expression and sensitivity to LPS-mediated
      apoptosis.

PMID- 11228164
TI  - Shedding of c-Met is regulated by crosstalk between a G-protein coupled receptor
      and the EGF receptor and is mediated by a TIMP-3 sensitive metalloproteinase.
AB  - A wide repertoire of transmembrane proteins are proteolytically released from the
      cell surface by a process known as 'ectodomain shedding', under both normal and
      pathophysiological conditions. Little is known about the physiological mechanisms
      that regulate this process. As a model system, we have investigated the
      metalloproteinase-mediated cleavage of the hepatocyte growth factor receptor,
      Met. We show that epidermal growth factor (EGF) receptor activation, either
      directly by EGF or indirectly via the G-protein coupled receptor (GPCR) agonist
      lysophosphatidic acid (LPA), induces cleavage of Met through activation of the
      Erk MAP kinase signalling cascade. The tyrosine kinase activity of the EGFR was a
      prerequisite for this stimulation, since treatment of cells with a synthetic
      inhibitor of this receptor, AG1478, completely abrogated shedding. The
      metalloproteinase mediating Met cleavage was specifically inhibited by the tissue
      inhibitor of metalloproteinases (TIMP)-3, but not by TIMP-1 or TIMP-2.
      Furthermore, the level of Met shedding could be modulated by different cell
      matrix interactions. Our results indicate that ectodomain shedding is a highly
      regulated process that can be stimulated by EGFR signalling pathways and integrin
      ligation.

PMID- 11228165
TI  - Rap1 is involved in cell stretching modulation of p38 but not ERK or JNK MAP
      kinase.
AB  - Mechanical force or mechanical stress modulates intracellular signal pathways,
      including the mitogen-activated protein kinase (MAP kinase) cascades. In our
      system, cell stretching activated and cell contraction inactivated all three MAP
      kinase pathways (MKK1/2-extracellular signal-regulated kinase (ERK), MKK4 (SEK1)
      cJun N-terminal kinase (JNK) and MKK3/6-p38 pathways). However, little is known
      about the molecular mechanisms that link the mechanical force to the MAP kinase
      cascades. To test whether Ras and Rap1 are possible components in the stretch
      activated MAP kinase pathways, we examined if Ras and Rap1 were activated by cell
      stretching and if inhibition of their activity decreased the stretch-enhanced MAP
      kinase activity. Rap1 was activated by cell stretching and inactivated by cell
      contraction, whereas Ras was inactivated by cell stretching and activated by cell
      contraction. Rap1GapII and SPA-1, downregulators of Rap1 activity, decreased the
      stretch-enhanced p38 activity, whereas a dominant-negative mutant of Ras (RasN17)
      did not inhibit the stretch-initiated activation of MAP kinases. Furthermore,
      overexpression of Rap1 enhanced p38 activity but not ERK or JNK activity. These
      results indicate that Rap1 is involved in transducing the stretch-initiated
      signal to the MKK3/6-p38 pathway, but not to the MEK1/2-ERK or the MKK4
      (SEK1)/MKK7-JNK pathway. Thus, Rap1 plays a unique role in force-initiated signal
      transduction.

PMID- 11228166
TI  - VEGF transiently disrupts gap junctional communication in endothelial cells.
AB  - Vascular endothelial growth factor, VEGF, stimulates angiogenesis by directly
      acting on endothelial cells. The effects of VEGF are mediated by two tyrosine
      kinase receptors, VEGFR-1 (Flt-1) and VEGFR-2 (Flk-1/KDR) that are highly related
      to receptors of the platelet derived growth factor (PDGF) receptor family. We are
      interested in early signalling events downstream from VEGF receptors that affect
      blood vessel homeostasis. Endothelial cells form multiple types of cell-cell
      junctions that are required for cellular organization into complex networks.
      These junctions also regulate communication among adjacent cells. Stimulation by
      various growth factors such as epidermal growth factor (EGF) or PDGF has been
      shown to disrupt cell-cell junctions, consequently affecting cell-to-cell
      communication. We investigated gap junctional communication (GJC) by monitoring
      the transfer of a low molecular mass fluorescent tracer molecule between adjacent
      cells using immunofluorescence microscopy. VEGF maximally blocked GJC 15 minutes
      after growth factor administration. The cells resumed communication via gap
      junctions within 1-2 hours after treatment. This early effect of VEGF on
      communication correlated with changes in the phosphorylation state of one of the
      proteins involved in gap junction formation, connexin 43 (Cx43). The signalling
      mechanisms involved in this phenomenon depend on activation of VEGFR-2, impinge
      on a tyrosine kinase of the Src family and activate the Erk family of MAP
      kinases. The function of VEGF-mediated disruption of GJC might be to restrict an
      increase in endothelium permeability to the environment affected by local injury
      to blood vessels.

PMID- 11228167
TI  - Mutant cadherin affects epithelial morphogenesis and invasion, but not
      transformation.
AB  - MDCK cells were engineered to reversibly express mutant E-cadherin protein with a
      large extracellular deletion. Mutant cadherin overexpression reduced the
      expression of endogenous E- and K-cadherins in MDCK cells to negligible levels,
      resulting in decreased cell adhesion. Despite severe impairment of the cadherin
      adhesion system, cells overexpressing mutant E-cadherin formed fluid-filled cysts
      in collagen gel cultures and responded to hepatocyte growth factor/scatter factor
      (HGF/SF) that induced cellular extension formation with a frequency similar to
      that of control cysts. However, cells were shed from cyst walls into the lumen
      and into the collagen matrix prior to and during HGF/SF induced tubule extension.
      Despite the propensity for cell dissociation, MDCK cells lacking cadherin
      adhesion molecules were not capable of anchorage-independent growth in soft agar
      and cell proliferation rate was not affected. Thus, cadherin loss does not induce
      transformation, despite inducing an invasive phenotype, a later stage of tumor
      progression. These experiments are especially relevant to tumor progression in
      cells with altered E-cadherin expression, particularly tumor samples with
      identified E-cadherin extracellular domain genomic mutations.

PMID- 11228168
TI  - Renal replacement therapy in the patient with acute brain injury.
AB  - The patient with an acute brain injury requiring renal replacement therapy
      presents a major problem in that conventional intermittent hemodialysis may
      exacerbate the injury by compromising cerebral perfusion pressure, either after a
      reduction in cerebral perfusion or because of increased cerebral edema. Compared
      with standard intermittent hemodialysis, the continuous forms of renal
      replacement therapy (CRRT) provide an effective therapy in terms of solute
      clearance, coupled with improved cardiovascular and intracranial stability. The
      disadvantage of CRRT is that anticoagulation may be required, and anticoagulants
      with systemic effects may provoke intracerebral hemorrhage, either at the site of
      damage or around the intracranial pressure monitoring device. Although peritoneal
      dialysis does not require anticoagulation, the clearances achieved are often less
      than those of CRRT, and sudden changes in intraperitoneal volume may provoke
      cardiovascular and thus intracranial instability.

PMID- 11228169
TI  - Intrauterine food restriction as a determinant of nephrosclerosis.
AB  - We previously showed that 3-month-old rats subjected to a 50% intrauterine food
      restriction had a decreased number of nephrons with increased glomerular
      diameter, which suggests compensatory hypertrophy. Hypertrophy could be the early
      event of glomerular damage. In this study, we extended our investigation and
      performed functional, morphological, and immunohistochemical evaluations in 3-
      and 18-month-old rats that underwent a 50% intrauterine food restriction (RT3 and
      RT18, respectively) and age-matched control rats (C3 and C18, respectively). Our
      findings showed that glomerular filtration rate was significant decreased in RT18
      rats (2.42 +/- 0.15 mL/min/kg; n = 28; P: < 0.05) compared with C18 control rats
      (4.19 +/- 0.10 mL/min/kg; P: < 0.05) and the percentage of glomeruli with
      sclerosis was greater in RT18 rats (13.01% +/- 2.95%; n = 9; P: < 0.01) than in
      C18 rats (2.71% +/- 0.35%; n = 6). RT18 rats also showed more intense
      tubulointerstitial lesions and immunohistochemical alterations in the renal
      cortex. Immunohistochemical studies showed increased fibronectin and desmin
      expression in glomeruli and tubulointerstitium and increased vimentin and alpha
      smooth muscle actin in the tubulointerstitial area from the renal cortex of RT18
      rats (P: < 0.05). Desmin was also increased at the edge of glomeruli from RT18
      rats, suggesting podocyte injury. Our data show that when food restriction is
      imposed during pregnancy, permanent damage occurs in the kidney of the offspring.
      Glomerular lesions were more severe than the tubulointerstitial damage in these
      animals.

PMID- 11228170
TI  - Late escape from the antiproteinuric effect of ace inhibitors in nondiabetic
      renal disease.
AB  - Angiotensin-converting enzyme (ACE) inhibitors exert a renoprotective effect in
      both diabetic and nondiabetic renal disease with variable efficacy. Proteinuric
      patients with nondiabetic renal disease, normotension, and restricted protein and
      sodium intake were treated with ACE inhibitors without diuretics. Fifty-nine
      patients were treated with either lisinopril (10 mg/d; 36 patients) or enalapril
      (5 mg/d; 23 patients) over a period of 37.7 +/- 20.7 months. Urinary protein
      excretion decreased to less than 50% of pretreatment values after 1 to 37 months
      (6.9 +/- 8.8 months) of therapy in 33 patients (56%); in 29 patients, it reached
      less than 0.5 g/d of protein. Urinary protein levels remained low in 19 of the 33
      patients (57.5%) throughout the entire posttreatment period (30.8 +/- 17.7
      months). However, in the remaining 14 patients, escape from the antiproteinuric
      effect was detected after 19.2 +/- 13.4 months, evidenced by a decrease in the
      rate of change in creatinine clearance from 0.052 +/- 0.114 mL/min/mon during the
      low-proteinuria period to -0.697 +/- 1.101 mL/min/mon after the lapse of
      antiproteinuric effect (P: < 0.001). Although ACE inhibitors reduce the severity
      of proteinuria in patients with nondiabetic renal disease, our results show that
      a proportion of patients escape the antiproteinuric effect and subsequently
      develop an exacerbation of renal dysfunction.

PMID- 11228171
TI  - Cardiac risk factors and the use of cardioprotective medications in patients with
      chronic renal insufficiency.
AB  - Cardiovascular disease (CVD) is a major cause of morbidity and mortality among
      patients with chronic renal insufficiency (CRI). beta-Adrenergic blockers,
      acetylsalicylic acid (ASA), angiotensin-converting enzyme (ACE) inhibitors, and 3
      hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) all reduce CVD
      mortality, but little is known about the extent to which these medications are
      used in patients with CRI. This study, a prospective cross-sectional study of
      consecutive patients seen by nephrologists in four Canadian centers for follow-up
      of progressive CRI in 1999, was performed to investigate the prevalence of
      coronary risk factors and use of cardioprotective medications among patients with
      CRI. Patients had creatinine clearances of 75 mL/min or less but were not on
      dialysis therapy. Three hundred four consecutive patients meeting the inclusion
      criteria were enrolled. Mean age was 60.8 +/- 15.7 years, mean creatinine
      clearance was 30.3 +/- 18 mL/min, and the case mix of kidney diseases was similar
      to that in the Canadian Organ Replacement Registry data. One hundred seventeen of
      304 patients (38.5%) had a history of previous CVD, and the prevalence of CVD was
      greater in patients with more severe CRI. Two hundred forty-three patients
      (79.9%) had a history of hypertension, 132 patients (43.4%) had hyperlipidemia,
      114 patients (37.5%) had diabetes mellitus, and 71 patients (27.3%) were smokers.
      Thirty-five percent of the patients with CVD had blood pressures greater than
      140/90 mm Hg; 103 patients (33.9%) were administered beta-blockers; 196 patients
      (64.5%), ACE inhibitors or angiotensin-receptor blockers; 83 patients (27.3%),
      ASA; and 56 patients (18.4%), statins. Patients with diabetes were not more
      likely than those without diabetes to be prescribed cardioprotective medications.
      CVD is common in the predialysis population, and its prevalence increases with
      more severe kidney failure. Despite this, the use of cardioprotective medications
      is relatively low, and many patients had suboptimal blood pressure control. Given
      the high burden of disease in these patients, beta-blockers and ACE inhibitors
      should be used to control hypertension and/or for cardioprotection, and the
      increased use of ASA and statins should be considered.

PMID- 11228172
TI  - Anti-C1q antibodies may help in diagnosing a renal flare in lupus nephritis.
AB  - It is still uncertain which, if any, immunologic parameters may help diagnose a
      renal flare of lupus nephritis. Anti-C1q antibody (Ab) titers have been elevated
      in patients with lupus with renal involvement, but little information is
      available on whether the titers are different in quiescent and active phases of
      lupus nephritis. In this study, we compared anti-C1q Ab titers with other
      serological test results in 48 patients with biopsy-proven lupus nephritis to
      assess which parameter could offer the best reliability for differentiating
      between quiescent and active phases of lupus nephritis. Serum C3 and C4 levels,
      as well as anti-double-stranded DNA, antiendothelial cell, anti-C1q, and
      antiphospholipid Ab titers, were evaluated in patients with quiescent renal
      disease (38 samples) and those with clinical evidence of renal activity (23
      samples). Only anti-C1q Ab titers correlated with active renal disease in both
      univariate (P < 0.0001) and multivariate analysis (P < 0.0001), with a
      sensitivity of 87% and a specificity of 92%. In six patients, immunologic
      parameters were measured serially. In all patients, the high anti-C1q Ab titers
      returned to normal values after treatment-induced remission. The other
      serological parameters did not show a significant association with renal disease
      activity. In patients with biopsy-proven lupus nephritis, anti-C1q Ab titers
      appear to be strongly related to renal disease activity. Their measurement may be
      useful for confirming the diagnosis of renal flares of lupus nephritis.

PMID- 11228173
TI  - Two sporadic cases of Liddle's syndrome caused by De novo ENaC mutations.
AB  - Liddle's syndrome is a rare form of hereditary hypertension caused by mutations
      of the epithelial sodium (Na(+)) channel (ENaC). Analysis of the diseased
      pedigrees indicates an autosomal dominant inheritance, and the identified
      mutations are heterozygotes of gain-of-function mutations. However, sporadic
      cases of Liddle's syndrome have been reported in the literature, including one
      recently reported case caused by a de novo mutation of ENaC. We identified two
      patients with Liddle's syndrome who did not have family histories of
      hypertension. Sequence analysis showed a mutation in each case (P616L in betaENaC
      and W576X in gammaENaC), both confirmed to be de novo mutations. These data
      indicate that Liddle's syndrome should be considered even in patients without a
      family history of hypertension.

PMID- 11228174
TI  - Branchio-Oto-renal syndrome: a report on nine family groups.
AB  - This study reviews nine new families with branchio-oto-renal (BOR) syndrome
      (Online Mendelian Inheritance in Man [OMIM] 113650). Diagnosis was made by
      studying 10 index cases, and then 22 other previously undetected patients were
      diagnosed within the nine families. The syndrome consists of conductive,
      sensorineural, or mixed hearing loss; preauricular pits; structural defects of
      the outer, middle, or inner ear; renal anomalies; lateral cervical fistulas,
      cysts, or sinuses; and/or nasolacrimal duct stenosis or fistulas. In our study,
      all patients first diagnosed in each familial group were recognized on the basis
      of severe renal anomalies associated with at least one of these symptoms. Our
      study showed that BOR syndrome is a misdiagnosed disorder, usually recognized in
      the presence of severe renal failure but often not diagnosed, especially in the
      adult in the presence of other isolated clinical signs, such as mild branchial or
      urological anomalies. We stress the meticulous search we performed for renal
      anomalies and/or hearing loss in all subjects showing minimal signs of branchial
      defects. BOR syndrome should be suspected in all cases of isolated urological
      anomalies, even if no other signs of the syndrome are present. After BOR syndrome
      has been diagnosed in a patient, all family members should be examined for the
      presence of the syndrome, even if there are only minimal stigmata of the disease.

PMID- 11228175
TI  - Coadministration of ketoconazole and cyclosporine for kidney transplant
      recipients: long-term follow-up and study of metabolic consequences.
AB  - In a prospective randomized study including 100 kidney transplant recipients, we
      previously reported on the safety and financial benefits of the coadministration
      of ketoconazole (keto) to cyclosporine (CsA)-treated kidney transplant
      recipients. In this study, we report on the long-term follow-up of these patients
      and their control group, as well as possible metabolic consequences of this drug
      combination. Evaluation of 51 keto-treated patients and their control group (49
      patients) included graft function, lipogram, fasting blood glucose, liver
      function tests, serum calcium, phosphorus, and radiological and histopathologic
      assessments. Follow-up of these patients for 54 months showed that the CsA dose
      reduction was 72.9% at 12 months, decreased to 69.3% at the last follow-up. We
      also found that the mean keto dose required for CsA dose reduction decreased to
      82.8 +/- 24.1 mg/d compared with the starting dose (100 mg/d). Diagnosis of acute
      rejection episodes was similar in both groups. However, in the control group,
      rejection episodes were more recurrent, with poorer response to treatment. Acute
      CsA nephrotoxicity was more common in the keto group, but this was encountered
      more at keto induction and was rapidly reversed on further reduction of CsA
      doses. Chronic graft dysfunction was statistically significantly less in the keto
      group during the first year. However, by the end of the study, the difference was
      not statistically significant. In this study, hepatotoxicity was similar in the
      two groups. On studying the metabolic consequences, we found that serum
      cholesterol, low-density lipoprotein, and triglyceride levels were lower in the
      keto group. Bone mineral contents in both groups were less than the mean values
      for age- and sex-matched healthy controls. From this study, we conclude that long
      term use of low-dose keto in CsA-treated kidney transplant recipients is safe and
      cost-saving and may induce better graft function. Bone mineral contents, vitamin
      D blood levels, and lipid profiles are not affected by long-term keto
      coadministration in CsA-treated kidney transplant recipients.

PMID- 11228176
TI  - Expression of chemokines and chemokine receptors during human renal transplant
      rejection.
AB  - Infiltration of renal allografts by leukocytes is a hallmark of acute transplant
      rejection. Chemokines attract leukocytes bearing specific chemokine receptors,
      and the specific leukocyte chemokine receptor phenotype is associated with types
      of immune responses, ie, T helper subtype 1 (Th1; CXC chemokine receptor 3
      [CXCR3], CC chemokine receptor 5 [CCR5]) versus Th2 (CCR3, CCR4, CCR8). We
      studied the expression of the chemokine monocyte chemoattractant protein-1 and
      the chemokine receptors CCR2B and CXCR4 messenger RNA (mRNA) by in situ
      hybridization, as well as the chemokine receptors Duffy antigen receptor for
      chemokines (DARC) and CCR5 protein by immunohistochemistry in renal biopsy
      specimens with acute cellular rejection (n = 12) and acute vascular rejection (n
      = 8), transplant nephrectomy specimens (n = 6), and normal areas of tumor
      nephrectomy specimens (n = 5). CC chemokines and CC chemokine receptor mRNA
      expression were evaluated by ribonuclease protection assay in specimens from four
      transplant nephrectomies and one tumor nephrectomy. Upregulation of mRNAs for the
      chemokines, interferon-inducible protein-10 (IP-10); regulated on activation
      normal T-cell expressed and secreted; macrophage inflammatory protein-1alpha (MIP
      1alpha); MIP-1beta; and lymphotactin, as well as the chemokine receptors, CCR2
      and CCR5, were documented during allograft rejection. CCR1 mRNA was detectable in
      both allografts and controls, but CCR3 and CCR8 were absent. The number of CXCR4,
      CCR5, and CCR2B mRNAs expressing leukocytes and DARC-positive vessels increased
      during rejection episodes. CXCR4 mRNA was the most widely expressed. Leukocytes
      in diffuse interstitial infiltrates were mainly CCR5 positive, but in areas in
      which leukocytes formed nodular aggregates of infiltrating cells, the number of
      CCR5-positive cells was low. Instead, leukocytes in these nodular aggregates
      mainly expressed CXCR4. DARC was expressed on peritubular capillaries, where it
      was upregulated in areas of interstitial infiltration. Induction of chemokines
      during renal allograft rejection is accompanied by infiltration of leukocytes
      bearing the respective chemokine receptors. The upregulation of the CXCR3 ligand
      IP-10, as well as CCR5 and its ligands, in the absence of CCR3 and CCR8 is
      indicative that renal allograft rejection is primarily the result of a Th1-type
      immune response.

PMID- 11228177
TI  - Efficacy and side effects of intermittent intravenous and oral doxercalciferol
      (1alpha-hydroxyvitamin D(2)) in dialysis patients with secondary
      hyperparathyroidism: a sequential comparison.
AB  - Most reports on the effectiveness and side effects of oral versus parenteral
      calcitriol or alfacalcidol in hemodialysis patients with secondary
      hyperparathyroidism show no advantage of parenteral treatment. The efficacy and
      safety of intravenous doxercalciferol (1alphaD(2)) were studied in hemodialysis
      patients with secondary hyperparathyroidism (plasma intact parathyroid hormone
      [iPTH]: range, 266 to 3,644 pg/mL; median, 707 pg/mL). These results were
      compared with those of a previous trial using intermittent oral 1alphaD(2); the
      same 70 patients were entered onto both trials, and 64 patients completed both
      trials per protocol. Twelve weeks of open-label treatment in both trials were
      preceded by identical 8-week washout periods. Degrees of iPTH suppression from
      baseline were similar in the two trials, with iPTH level reductions less than 50%
      in 89% and 78% of patients during oral and intravenous treatment, respectively.
      Grouping patients according to entry iPTH levels (<750 and >/=750 pg/mL) showed
      similar but more rapid iPTH suppression in the low-iPTH groups, whereas longer
      treatment and larger doses were required by the high-iPTH groups. Highest serum
      calcium levels averaged 9.82 +/- 0.14 and 9.67 +/- 0.11 mg/dL during oral and
      intravenous 1alphaD(2) treatment, respectively (P: = not significant [NS]).
      Prevalences of serum calcium levels greater than 11.2 mg/dL during oral and
      intravenous treatment were 3.62% and 0.86% of calcium measurements, respectively
      (P: < 0.001). Highest serum phosphorus levels during oral and intravenous
      treatment averaged 5.82 +/- 0.21 and 5.60 +/- 0.21 mg/dL, respectively (P: = NS).
      The percentage of increments in serum phosphorus levels during oral treatment
      exceeded that during intravenous treatment during 5 of 12 treatment weeks. Thus,
      intermittent oral and intravenous therapy with 1alphaD(2) reduced iPTH levels
      effectively and similarly, hypercalcemia was less frequent, and serum phosphorus
      levels increased less during intravenous than oral 1alphaD(2) therapy, suggesting
      that intravenous 1alphaD(2) therapy may be advantageous in patients prone to
      hypercalcemia or hyperphosphatemia.

PMID- 11228178
TI  - Urea reduction ratio that considers effects of ultrafiltration and intradialytic
      urea generation.
AB  - We modified the urea reduction ratio (URR) equation to correct the effects of
      ultrafiltration and intradialytic urea generation on the delivered dose of
      hemodialysis: mURR = [1 - (R/1 + 2*UF/BW) + 0.01*t] x 100% where mURR is modified
      URR, R is postdialysis plasma urea nitrogen (PUN) to predialysis PUN ratio, UF is
      ultrafiltrate volume in liters, BW is postdialysis body weight in kilograms, and
      t is dialysis session length in hours. The equation was validated against 145
      hemodialysis treatments on 33 stable maintenance dialysis patients. The mURR
      values obtained closely predicted single-pool Kt/V (spKt/V) values. In contrast
      to conventional URR, the range of spKt/V values at each mURR value is narrow over
      a wide range of UF, t, and R values. Based on the mURR equation, mURR values of
      64%, 70%, and 76% are mathematically equivalent to spKt/V levels of 1.0, 1.2, and
      1.4, respectively. This equation can be a useful bedside tool to quantify
      hemodialysis dose.

PMID- 11228179
TI  - Assessment of erythropoiesis activity during hemodialysis therapy by soluble
      transferrin receptor levels and ferrokinetic measurements.
AB  - The erythropoietic activity (EA) and degree of erythropoiesis attained by
      patients undergoing hemodialysis (HD) administered recombinant human
      erythropoietin (rHuEPO) were studied using ferrokinetic measurements and tests of
      soluble transferrin receptor (sTfR) levels, assessing which parameter is most
      useful for measurements in clinical practice. Plasma iron 59 ((59)Fe) clearance
      (half-life [T(1/2)] (59)Fe), plasma iron turnover (PIT), erythron transferrin
      uptake (ETU), and erythrocyte (59)Fe incorporation were determined in 23 patients
      before and at 4 months after administration of rHuEPO. sTfR levels, hematopoietic
      parameters, and iron metabolism parameters were measured periodically. T(1/2)
      (59)Fe was shortened (P: = 0.004), PIT and ETU were increased (P: = 0.032 and P:
      = 0.013, respectively), and the time taken by erythrocytes to incorporate 80% of
      the (59)Fe administered was reduced from 9.6 to 6.1 days. sTfR levels were
      increased by 15 days; this increase was significant (P: < 0.05) at 30 days,
      reaching a maximum of 3.22 mg/dL at day 45. A positive correlation was seen
      between sTfR levels and hemoglobin (Hb) (P: = 0.001), hematocrit (P: = 0.001),
      and reticulocytes (P: = 0.038) that was not found between ferrokinetic parameters
      and those evaluating efficient erythropoiesis (P: = 0.345 between ETU and Hb). In
      conclusion, EA is increased, shown by ETU and sTfR level. sTfR levels correlate
      with the parameters that evaluate efficient erythropoiesis, and their measurement
      does not involve the technical and/or ethical limitations of studies of
      ferrokinetics, making them the tool of choice in clinical practice for the
      evaluation of EA in patients undergoing HD administered rHuEPO.

PMID- 11228180
TI  - Comparison of cuffed tunneled hemodialysis catheter survival.
AB  - Despite efforts to have hemodialysis patients begin renal replacement therapy
      with a mature arteriovenous shunt, many patients begin dialysis with a cuffed
      tunneled catheter as their access. An increasing number of differently designed
      tunneled hemodialysis catheters have become available in the last decade. The
      primary aim of this study is to compare catheter survival for Hickman (Bard, Salt
      Lake City, UT) and Opti-flow (Bard) catheters. The 16-month experience with 182
      catheters, totaling 13,861 catheter-days, is reported. The probability of Hickman
      catheter failure at 30, 60, and 90 days was 29%, 49%, and 67%. The probability of
      Opti-flow catheter failure was significantly less at 10%, 24%, and 38% for the
      same times, respectively (P: < 0.05 for all time points). The difference in
      catheter failure rates was caused by a greater malfunction rate of Hickman
      catheters; the two catheters had similar infection rates. We conclude that
      survival of Opti-flow catheters was significantly better than that of Hickman
      catheters from 30 to 90 days, which is a clinically relevant period when patients
      are waiting for maturation of a permanent access or replacement of a failed
      access. Since the conclusion of our study, we documented 10 episodes of Opti-flow
      catheter malfunction within 4 months secondary to hairline fracture of the
      arterial hub. The Opti-flow catheter was recalled and is now available with
      retooled hubs.

PMID- 11228181
TI  - Serum ferritin is a marker of morbidity and mortality in hemodialysis patients.
AB  - We tested the hypothesis that a high concentration of serum ferritin, a
      frequently used marker of iron stores in dialysis patients and an acute-phase
      reactant, may be a marker of morbidity and mortality in these patients. To
      evaluate the impact of ferritin on morbidity and mortality, we reviewed the 6
      month hospitalization rates in our dialysis patients retrospectively and
      subsequently reviewed the mortality among these patients over a 12-month period
      of time prospectively. One hundred one adult hemodialysis patients (59 men and 42
      women; age, 54 +/- 15 years) who had been on hemodialysis for 38 +/- 27 months
      were studied. All but 5 patients were on intravenous iron with similar iron
      administration pattern. In the retrospective cohort, ferritin's correlation
      coefficients for hospitalization days and frequency (both r = +0.39, P: < 0.001)
      were higher compared with the albumin correlations for hospitalization days (r = 
      0.31, P: = 0.001) and frequency (r = -0.28, P: = 0.005) and correlation
      coefficients remained similarly significant after case-mix adjustment. In the
      prospective study, the "predeath" value of serum ferritin for 17 deceased
      patients (891 +/- 476 ng/mL) was higher than both their "initial" value (619 +/-
      345 ng/mL, P: = 0.007) and the mean ferritin value of 84 surviving and
      withdrawing patients (639 +/- 358 ng/mL, P: = 0.001). Although Cox proportional
      hazard analysis showed a significant odds ratio of death only for serum albumin
      and not for ferritin, logistic regression analysis using the predeath values
      confirmed the significant impact of both decreased serum albumin and increased
      serum ferritin as markers of dialysis mortality. After case-mix adjustment, the
      relative risks of death for a 500 ng/dL increase in serum ferritin was 2.71 (95%
      confidence interval, 1.06 to 7.02) and for a 0.5 g/dL decrease in serum albumin
      was 4.48 (95% confidence interval, 1.77 to 11.33). Hence, serum ferritin is a
      strong predictor of hospitalization in dialysis patients. Although serum albumin
      is found to be a strong long-term marker of mortality in hemodialysis patients,
      an increase in serum ferritin appears to be a more reliable short-term marker of
      death over a 12-month period. Therefore, in the setting of uniform iron
      administration, a high serum ferritin may be a morbidity risk factor and a recent
      increase in serum ferritin may carry an increase in the risk of death in these
      patients.

PMID- 11228182
TI  - Risk factors for mortality in infants and young children on dialysis.
AB  - The factors associated with a greater mortality risk in infants and young
      children undergoing dialysis have not been clearly determined. We report the
      results of a North American Pediatric Renal Transplant Cooperative Study designed
      to assess risk factors in patients aged younger than 6 years at initiation of
      dialysis therapy. Sixty-four nonsurvivors were matched with 110 survivors for age
      at dialysis initiation, primary renal disease, and year of entry onto the
      database. Questionnaires on 137 patients (51 nonsurvivors, 86 survivors) were
      completed by participating centers. Seventy-five percent (103 of 137 patients) of
      the patients were aged younger than 2 years at dialysis initiation; 42% (58 of
      137 patients) had renal aplasia, dysplasia, and/or hypoplasia or obstructive
      uropathy; 62% were boys; and 62% were white. One-year patient survival rates were
      83% in infants beginning dialysis at younger than 3 months of age, 89% in 3- to
      23-month-olds, and 95% in 2- to 5-year-olds (P = 0.001). Comorbid nonrenal
      disease occurred in 37 of 51 nonsurvivors (74%) versus 46 of 84 survivors (55%; P
      = 0.027). Nonsurvivors had pulmonary disease and/or hypoplasia more often (14 of
      37 nonsurvivors; 37.8% versus 8 of 46 survivors; 17.4%; P = 0.04). Oliguria or
      anuria was present in 23 of 33 nonsurvivors (70%) aged younger than 2 years
      versus 26 of 64 survivors (41%; P = 0.007). Infection accounted for 15 of 51
      deaths (29.4%). In summary, these results suggest that age at dialysis
      initiation; presence of nonrenal disease, particularly pulmonary disease and/or
      hypoplasia; and oliguria or anuria in children aged younger than 2 years are
      identifiable as risk factors for mortality in these young patients.

PMID- 11228183
TI  - Continuous peritoneal dialysis and the extended care facility.
AB  - The projected disproportionate increase in the number of elderly patients
      reaching end-stage renal disease constitutes a dramatic change in dialysis
      demographics. The nursing home or extended care facility (ECF) will become an
      increasingly important feature of care for both rehabilitation and long-term
      patient management. For continuous peritoneal dialysis (CPD), the ECF has been
      critically evaluated in only a single specialized, university-based, geriatric
      facility that included trained peritoneal dialysis nurses providing care. We have
      trained multiple ECF personnel in 10 community-based ECFs to provide all CPD
      related therapy for 93 patients between November 1993 and December 1998, for a
      total of 289.3 patient-months. All ECFs have maintained their CPD program.
      Outcome measures, including hospitalization, mortality, technique failure, and
      peritonitis rates, show the success and feasibility of using community-based ECFs
      for CPD. The use of multiple ECFs for CPD appears to offer distinct advantages
      over solo structured ECF programs without jeopardizing outcomes. A highly
      structured CPD education program for ECF personnel by nephrology staff is
      manageable and appears critical for the success of maintaining CPD in the ECF.

PMID- 11228184
TI  - Strict volume control normalizes hypertension in peritoneal dialysis patients.
AB  - The aim of this study is to investigate whether normal blood pressure (BP) can be
      achieved in patients with hypertension on continuous ambulatory peritoneal
      dialysis (CAPD) therapy by strict volume control without the use of
      antihypertensive drugs. Of the 78 patients in our center, 47 persons had
      hypertension and/or were on antihypertensive drug therapy. After discontinuing
      these drugs, a strong dietary salt restriction was imposed by repeatedly
      explaining the need for it to patients and families. If this approach did not
      result in sufficient BP decrease, ultrafiltration (UF) was added by increased use
      of hypertonic (3.86% glucose) peritoneal dialysis solution. Cardiothoracic index
      (CTI) on the chest radiograph was also used as a measure of volume control. With
      salt restriction alone or combined with UF, body weight decreased by a mean of
      2.8 +/- 0.5 kg, and BP decreased from a mean of 158.2 +/- 17.0/95.7 +/- 10.3 to
      119.7 +/- 16.0/77.9 +/- 9.7 mm Hg in 37 patients, accompanied by a decrease in
      CTI from 48.0% +/- 5.6% to 42.9% +/- 4.5%. In 19 patients who had residual renal
      function, 24-hour urine volume decreased to 28% of the pretreatment volume,
      accompanied by a mean decrease in Kt/V urea from 2.06 +/- 0.5 to 1.85 +/- 0.4. In
      7 of the remaining patients who did not respond to the applied treatment, BP
      decreased from 158.8 +/- 23.2/111.6 +/- 9.8 to 113.5 +/- 14.3/76.4 +/- 6.2 mm Hg
      after administration of an angiotensin-converting enzyme (ACE) inhibitor. Their
      CTI was 41.2% +/- 1.3%, indicating the absence of hypervolemia. In 3 patients,
      the desired results could not be reached because of noncompliance. Our findings
      show that normal BP can be achieved by severe salt restriction combined with
      increased UF in the majority of CAPD patients. This is accompanied by a decrease
      in CTI from upper limits into the normal range, but also by a decrease in
      residual renal function and Kt/V index. In most of the remaining patients, normal
      BP can be reached by the use of ACE inhibitors.

PMID- 11228185
TI  - Hyaluronan modifies inflammatory response and peritoneal permeability during
      peritonitis in rats.
AB  - The effect of high-molecular-weight hyaluronan (HA) on peritoneal and systemic
      inflammation and peritoneal permeability to water and solutes was studied during
      endotoxin-induced peritonitis in rats. Acute peritonitis was induced by adding
      lipopolysaccharide (LPS) to the dialysis fluid (Dianeal 3.86; Baxter Healthcare,
      Ireland, Castlebar). HA was added to the dialysis solution in a concentration of
      10 mg/dL. During 4- and 8-hour dwells of the dialysis fluid, we studied the
      intensity of peritoneal (dialysate) and systemic (blood) inflammation (dialysate
      cell count and differential, cytokine and HA levels), as well as the
      transperitoneal transport of solutes and water. In rats, the addition of LPS to
      the dialysis fluid induced changes in inflammatory reaction and transperitoneal
      transport similar to those seen in continuous ambulatory peritoneal dialysis
      patients with peritonitis. During peritonitis, the addition of HA to the dialysis
      fluid reduced the loss of ultrafiltration, which resulted in a greater peritoneal
      creatinine clearance during the 8 hours of dwell (29.9 +/- 6.7 mL/8 h in the HA
      LPS group versus 19.7 +/- 7.8 mL/8 h in the LPS group; P < 0.05). Dialysate
      interferon-gamma (INF-gamma) levels during peritonitis were greater in HA-treated
      animals (536.8 +/- 296.6 pg/mL in the HA-LPS group versus 169.8 +/- 137.8 pg/mL
      in the LPS group; P < 0.05). Dialysate elastase activity increased during
      peritonitis (44.4 +/- 9.3 versus 14.2 +/- 4.1 U/mL in peritonitis-free rats);
      during peritonitis, the increase in dialysate elastase activity was less
      pronounced in the rats that had HA in the dialysate (27.3 +/- 4.1 U/mL versus the
      LPS group; P: < 0.01). We conclude that HA added to the dialysis fluid reduces
      loss of ultrafiltration during peritonitis in rats. In the presence of HA
      dialysate, INF-gamma levels during peritonitis increased, whereas elastase
      activity decreased; these changes might improve the peritoneal immune reaction
      during peritonitis and at the same time prevent peritoneal membrane injury.

PMID- 11228187
TI  - Screening a living kidney donor for polycystic kidney disease using heavily T2
      weighted MRI.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) accounts for approximately
      8% of those awaiting renal transplantation. Living related kidney donors for
      these patients require screening for ADPKD, most commonly by ultrasonography.
      Ultrasound has a negative predictive value (NPV) of 100% in patients aged older
      than 30 years, but only 96% for donors aged 20 to 30 years. This case shows that
      heavily T2-weighted magnetic resonance imaging (HT2MRI) may be a more sensitive
      screening method for ADPKD in younger kidney donors. Despite a normal screening
      ultrasound result, a kidney donor with a family history of ADPKD was found to
      have renal cysts intraoperatively, and the transplantation was canceled.
      Afterward, the donor was imaged with HT2MRI. In addition, the mathematical
      relationship between sensitivity, specificity, and NPV for ADPKD screening tests
      was derived. After the canceled transplantation, a second ultrasound still could
      not identify renal cysts. However, HT2MRI showed multiple small ( approximately 3
      mm) cysts in both kidneys and a 2.5-cm cyst on the right kidney. Mathematical
      analysis showed that the NPV of a screening test for ADPKD was most closely
      related to sensitivity and that only tests with 100% sensitivity would have a
      100% NPV. We conclude that ultrasound is not a sufficiently sensitive screening
      test for ADPKD in younger living related renal donors. HT2MRI has improved
      sensitivity and may be the best screening test for ADPKD in this population.

PMID- 11228186
TI  - Impaired angiogenesis in the aging kidney: vascular endothelial growth factor and
      thrombospondin-1 in renal disease.
AB  - We investigated the relationship of changes in the microvasculature to age
      related structural and functional changes in the kidney to determine whether
      there was evidence of impaired angiogenesis and whether the loss of
      microvasculature could be accounted for by changes in the local production of
      angiogenic or antiangiogenic factors. Glomerular and peritubular capillary
      number, density, and endothelial cell proliferation were determined in aging (24
      months; n = 9) and young (3 months; n = 8) rat kidneys and correlated with renal
      functional and structural changes and alterations in renal expression of vascular
      endothelial growth factor (VEGF) and thrombospondin-1 (TSP-1). Aging rats showed
      a focal decrease in both peritubular capillary (peritubular capillary staining,
      5.4% +/- 1.8% versus 11.3% +/- 2.0% per 100 tubules; rarefaction index, 10.6% +/-
      4.6% versus 0.6% +/- 0.1%, aging versus young rats; P < 0.05 and P: < 0.001,
      respectively) and glomerular capillary loops (27.3 +/- 6.9 versus 50.7 +/-
      7.4/glomerulus, aging versus young rats; P < 0.001). The number of proliferating
      endothelial cells was decreased in aging rats compared with young rats
      (glomerular, 0.04 +/- 0.01 versus 0.15 +/- 0.03 positive cells/glomerular cross
      section; peritubular, 0.7 +/- 0.2 versus 4.3 +/- 2.6 positive cells/mm(2); P <
      0.05). In the aging kidney, VEGF expression was focally increased in the cortex
      compared with young rats, whereas a profound decrease was observed in the outer
      and inner medulla (total area of VEGF expression, 19.2% +/- 11.4% versus 39.3% +/
      7.6%; P < 0.05). Tubular VEGF expression correlated with peritubular capillary
      density (r(2) = 0.57; P < 0.01) and inversely correlated with tubular osteopontin
      (r(2) = -0.55; P < 0.05) and macrophage infiltration (r(2) = -0.64; P < 0.01).
      TSP-1 staining was increased in the glomeruli and tubulointerstitium of the aging
      rats. Glomerular TSP-1 score correlated inversely with glomerular capillary
      number (r(2) = -0.89; P < 0.001). Tubulointerstitial TSP-1 also correlated with
      percentage of positive staining of peritubular capillary (r(2) = -0.59; P <
      0.001). Glomerular capillary number showed significant correlation with
      glomerulosclerosis score, as well as with 24-hour urinary protein excretion.
      Peritubular capillary density also inversely correlated with interstitial
      fibrosis score and urinary protein excretion. In conclusion, glomerular and
      peritubular capillary loss in the aging kidney correlate with alterations in VEGF
      and TSP-1 expression and also with the development of glomerulosclerosis and
      tubulointerstitial fibrosis. These findings suggest that impaired angiogenesis
      associated with progressive loss in renal microvasculature may have a pivotal
      role in age-related nephropathy.

PMID- 11228188
TI  - Propranolol rapidly reverses paralysis, hypokalemia, and hypophosphatemia in
      thyrotoxic periodic paralysis.
AB  - Hypokalemia and hypophosphatemia are commonly encountered during paralysis in
      patients with thyrotoxic periodic paralysis (TPP) and may contribute to
      neuromuscular manifestations. Potassium and phosphate supplements have been
      recommended to hasten recovery and prevent cardiopulmonary complications.
      However, this recommendation has not yet proven efficacious. Hyperadrenergic
      activity has been implicated in the pathogenesis of TPP. We tested whether
      nonselective beta-blockers could terminate neuromuscular symptoms rapidly while
      reducing an intracellular shift of potassium and phosphate. We describe two
      patients who had an acute attack of TPP with characteristic hypokalemia and
      hypophosphatemia associated with low urinary potassium and phosphate excretion.
      After oral propranolol, 3 mg/kg, serum potassium and phosphate concentrations
      increased promptly in 2 hours in both patients, and there was complete
      amelioration of paralysis. No rebound hyperkalemia or hyperphosphatemia was
      detected. Given their efficacy in this pilot study, they should be considered as
      a first-line therapy for TPP.

PMID- 11228189
TI  - Holoprosencephaly and low molecular weight proteinuria: the human homologue of
      murine megalin deficiency.
AB  - We encountered a child with holoprosencephaly, pulmonary insufficiency, absent
      circulating vitamin D metabolites, mild albuminuria, and urinary excretion of
      vitamin D-binding protein. The child displayed a phenotype highly reminiscent of
      that observed in mice genetically deficient for megalin, a member of the low
      density lipoprotein receptor superfamily. Only the Guthrie card was available
      from the child; the DNA sufficed for a limited haplotype analysis. We were not
      able to implicate the megalin gene locus directly; however, the possibility of a
      functional megalin defect in this child remains. To the best of our knowledge,
      this patient represents the first report that pathologic abnormalities consistent
      with megalin deficiency are present in humans.

PMID- 11228190
TI  - Food intake and the kidney: The right amounts at the right times.

PMID- 11228191
TI  - Sporadic cases of Liddle's syndrome: clues to essential hypertension?

PMID- 11228192
TI  - Should man live by low-salt bread alone?

PMID- 11228193
TI  - A family-based strategy to identify genes for diabetic nephropathy.
AB  - Diabetic nephropathy (DN) clusters in families and specific ethnic groups,
      suggesting a genetic basis of disease transmission. Identification of DN
      susceptibility loci should reveal new therapeutic targets but requires accurate
      phenotyping. A powerful family-based strategy, which is novel to the pursuit of
      nephropathy genes in type 2 diabetes, is being used to collect a sample for
      candidate gene and genome scan analyses. Sib pairs that include DN index cases
      plus (1) sibs concordant for type 2 diabetes and DN (affected sib pairs [ASPs])
      and (2) sibs concordant for type 2 diabetes but discordant for DN (discordant sib
      pairs [DSPs]) are targeted specifically for recruitment. Type 2 diabetes and DN
      phenotype criteria for index cases include diabetes onset after 38 years of age,
      duration 10 years or longer, no initial insulin treatment, diabetic retinopathy,
      end-stage renal disease (ESRD), and history of nephrotic proteinuria. ESRD
      patients were screened by questionnaire and medical record review (n = 2114). Of
      666 patients with ESRD secondary to DN, 227 had a family history of ESRD, 150 had
      a living diabetic sib, and 124 families were enrolled. Sixty-five families, with
      86 diabetic relative pairs (69 sibs, 17 children), have been completely
      phenotyped. If nephropathy in diabetic sibs is defined as albuminuria greater
      than 0.3 g/24 h, 31 ASPs and 26 DSPs (diabetic sib with albuminuria <0.3 g/24 h)
      were identified. Applying more stringent criteria, only 12 ASPs (sib with
      diabetes >10 years, diabetic retinopathy, and nephrotic proteinuria) and 9 DSPs
      (sib with diabetes >10 years and normal urine albumin excretion) were identified.
      Extrapolating from the number of subjects recruited using stringent phenotyping
      criteria, nearly 10,000 ESRD patients are required for screening to achieve
      adequate statistical power for linkage analysis (80% power to detect locus
      specific relative risk of 2.2 at a lod score of 3.0). Careful phenotyping
      requires a large recruitment effort but is necessary to reduce population
      heterogeneity, a strategy that increases the likelihood of identifying DN loci.

PMID- 11228195
TI  - Classifying lupus nephritis: a 32-year-old woman with systemic lupus
      erythematosus and nephritic syndrome.

PMID- 11228194
TI  - Salt intake and body fluid volumes: have we learned all there is to know?

PMID- 11228198
TI  - Immunotactoid glomerulopathy characterized by steroid-responsive massive
      subendothelial deposition.
AB  - We report a case of immunotactoid glomerulopathy with unique histologic findings
      in serial biopsies. A 73-year-old man complained of developing general edema.
      Laboratory data on admission presented moderate renal dysfunction with nephrotic
      syndrome. There was no evidence of systemic disease that might cause secondary
      glomerulopathy. Light microscopy of the renal specimen revealed lobulation of
      glomerular tufts and massive endothelial deposition of hyaline-like periodic acid
      Schiff-positive substance with neutrophilic infiltration. The deposits were
      positive for immunoglobulin by immunohistochemical stains but negative for Congo
      red stain. Electron microscopy disclosed the deposition of microtubular structure
      (60 nm in diameter) predominantly in the subendothelial area and to some extent
      in the subepithelial and mesangial areas. Some of the tubules were extremely
      large (100 to 130 nm in diameter) and displayed a unique scroll structure in
      cross-section. The patient was treated with two sessions of plasma exchange and
      subsequent oral prednisolone (30 mg/d). Proteinuria and renal dysfunction
      improved significantly in the following 2 months. Second and third renal biopsies
      revealed disappearance of the deposit along with the improvement of proteinuria
      and renal dysfunction. Because similar microtubular structures were found in
      neutrophils in the glomerulus as well as in the urinary sediment, phagocytosis
      was suggested as a possible mechanism for removal of the deposit.

PMID- 11228199
TI  - Hemolytic uremic syndrome in an adolescent with Fusobacterium necrophorum
      bacteremia.
AB  - Microorganisms may produce substances that disrupt the interaction between
      platelets and vascular endothelium, which has been associated with atypical
      hemolytic uremic syndrome (HUS). We present the first reported case of
      Fusobacterium necrophorum bacteremia that presented initially with atypical HUS.
      Antimicrobial therapy eradicated the patient's bacteremia, and plasmapheresis
      restored platelet-endothelial homeostasis. Understanding the pathophysiologic
      mechanisms involved in atypical HUS would guide the development of more precise
      therapies.

PMID- 11228200
TI  - Optic neuropathy in uremia: an interdisciplinary emergency.
AB  - Optic neuropathy in uremia is rare. Although the consequences of optic neuropathy
      blindness or substantial loss of vision-are devastating, only a few cases have
      been reported by way of single case reports and case series studies. The reported
      patients are heterogeneous with regard to the cause of neuropathy. We report the
      case of a patient with uremic optic neuropathy and summarize the other cases
      reported in the literature so far. Based on the data available from these
      reports, we propose a classification system, which includes nonischemic
      neurotoxic uremic optic neuropathy; ischemic optic neuropathy, more specifically
      anterior ischemic optic neuropathy; and optic neuropathy as a result of drug side
      effects, benign intracranial hypertension, and optic neuritis. The immediate
      institution of dialysis and corticosteroid therapy and correction of anemia and
      relative hypotension can optimize the chances of visual recovery for these
      patients. Close collaboration among nephrologists, ophthalmologists, and
      neurologists is important in this interdisciplinary emergency.

PMID- 11228201
TI  - Approach to the patient with hypertension, unexplained hypokalemia, and metabolic
      alkalosis.
AB  - We present a patient with hypertension and hypokalemia secondary to an
      aldosterone-producing adenoma that was renin responsive (APARR). We discussed the
      sequential approach to the diagnosis of the different subtypes of primary
      aldosteronism and confirmed the presence of an APARR. The most common cause of
      primary aldosteronism is an aldosteronoma; functionally, these adenomas respond
      poorly to angiotensin II but show a brisk response to adrenocorticotropin
      hormone. They have a pattern of aldosterone level that declines in parallel with
      cortisol levels. Our patient had an APARR, with an increase of aldosterone in the
      upright posture. The unusual physiologic response, incidence, and clinical
      characteristics of APARR are reviewed.

PMID- 11228202
TI  - The prognostic role of the extent of Y microdeletion on spermatogenesis and
      maturity of Sertoli cells.
AB  - Substantial involvement of the Y chromosome in sexual development and
      spermatogenesis has been demonstrated. Over the last decade, varying extent of Y
      chromosome microdeletions have been identified among infertile patients with
      azoospermia or oligozoospermia. These microdeletions were clustered in three main
      regions named AZFa, AZFb, and AZFc. Analysis of the Y chromosome microdeletion
      was found to be of prognostic value in cases of infertility, both in terms of
      clinical management as well as for understanding the aetiology of the
      spermatogenesis impairment. However, the accumulated data are difficult to
      analyse, due to the variable extent of these deletions, the different sequence
      tagged sites (STS) used to detect the microdeletions, and the non-uniformity of
      the histological terminology used by different investigators. This debate
      discusses the chances of finding testicular spermatozoa in men with a varying
      extent of Y chromosome microdeletions. The genotype and germ cell findings in men
      with AZFa microdeletions as well as those that include more than a single AZF
      region are reviewed, as is the effect of Y chromosome AZF microdeletions on the
      maturity of the Sertoli cells.

PMID- 11228203
TI  - Molecular diagnosis of Y chromosome microdeletions in Europe: state-of-the-art
      and quality control.
AB  - The polymerase chain reaction (PCR) screening of microdeletions of the Y
      chromosome has become an important diagnostic step in the work-up of male
      infertility. However, there is no agreement about how this diagnosis should be
      performed. There are suggestions that the large variation in deletion frequency
      reported in the literature could be due to the various selection criteria of the
      patients analysed, although methodological aspects may play a role as well. As
      for other genetic diseases, molecular diagnosis of Y chromosome microdeletions
      should be controlled by adopting strict internal quality control measures and by
      participating in external quality assessment schemes. Such an external quality
      assessment project is presently being organized jointly by the European Academy
      of Andrology and the European Molecular Genetics Quality Network. Three
      preliminary trials have given a state-of-the-art picture of the diagnostic
      performance in various European laboratories, showing an overall rate of
      misdiagnosis of approximately 5% for both AZFb and AZFc regions, and providing
      data useful in the generation of guidelines for the molecular diagnosis of Y
      chromosome microdeletions.

PMID- 11228204
TI  - Human oocyte cryopreservation: new perspectives regarding oocyte survival.
AB  - The success of human oocyte cryopreservation depends on morphological and
      biophysical factors that could influence oocyte survival after thawing. Various
      attempts to cryopreserve human oocytes have been performed with contrasting
      results. Therefore the effect of some factors, such as the presence or absence of
      the cumulus oophorus, the sucrose concentration in the freezing solution and the
      exposure time to cryoprotectants, on human oocyte survival after thawing were
      investigated. The oocytes were cryopreserved in 1,2-propanediol added with
      sucrose, using a slow-freezing-rapid-thawing programme. After thawing, the
      oocytes were inseminated by intracytoplasmic sperm injection (ICSI) and the
      outcomes of insemination and subsequent embryo development were also recorded.
      The post-thaw cryosurvival rate was not different for the oocytes cryopreserved
      with their cumuli partially removed mechanically (56%) when compared with those
      cryopreserved with their cumuli totally removed enzymatically (53%). On the
      contrary, a significantly higher survival rate was obtained when the oocytes were
      cryopreserved in the presence of a doubled sucrose concentration (0.2 mol/l) in
      the freezing solution and the survival rate was even higher when the sucrose
      concentration was tripled (0.3 mol/l) (60 versus 82% P < 0.001). Furthermore, a
      longer exposure time (from 10.5 to 15 min) to cryoprotectants, before lowering
      the temperature, significantly increased the oocyte survival rate (P < 0.005).
      Intracytoplasmic sperm injection produced a good fertilization rate (57%) of
      thawed oocytes and a high embryo cleavage rate (91%) and a satisfactory embryo
      morphology was observed (14 and 34% for grade I and grade II embryos
      respectively).

PMID- 11228205
TI  - Development of antral follicles in human cryopreserved ovarian tissue following
      xenografting.
AB  - This study reports the first gross morphological and histological evidence of
      antral follicle development in human ovarian tissue following cryopreservation.
      Human ovarian tissue was cryopreserved using propanediol and sucrose and grafted
      under the renal capsule of bilaterally oophorectomized severe combined
      immunodeficient (SCID) mice. Follicles at all stages of development were observed
      in the grafted tissue whereas, prior to grafting, only primary and primordial
      follicles were present. Antral follicles were rarely observed on grafts examined
      <20 weeks after grafting either non-frozen tissue (fresh, 1/7) or cryopreserved
      tissue (0/11). In contrast, development of at least one antral follicle was
      evident on the majority of sites > or = 20 weeks after grafting (fresh 7/9,
      cryopreserved 18/24). Antral follicle diameters ranged from 0.1 to 5.0 mm.
      Histological examination of these antral follicles indicated normal follicular
      morphology, i.e. antral cavities encapsulated by concentric layers of theca and
      granulosa cells. Pedicles containing germinal vesicle oocytes were observed
      protruding from the granulosa cell layers. The development and morphology of the
      cryopreserved and fresh tissue following grafting was similar.

PMID- 11228206
TI  - In-vitro growth of murine pre-antral follicles after isolation from cryopreserved
      ovarian tissue.
AB  - The low temperature storage of ovarian tissue allows patients at risk of
      premature menopause to preserve their fecundity. One strategy for harvesting
      mature oocytes may be to isolate small follicles from the stroma for in-vitro
      culture. The aim of this study was to assess the survival and growth of murine
      follicles during in-vitro culture after isolation from tissue frozen-thawed in
      various cryoprotective agents. The effect of different seeding and thawing
      temperatures was also investigated. Pre-antral follicles 100--135 microm in
      diameter were isolated from fresh and frozen-thawed tissue and cultured in vitro
      for 8 days. In the fresh control group 79 +/- 3% of follicles survived in-vitro
      culture and grew to antral stages. Fewer follicles survived after isolation from
      tissue cryopreserved in dimethyl sulphoxide (43 +/- 5%) or propylene glycol (24
      +/- 2%) and none survived freeze-thawing in glycerol. Lowering the seeding
      temperature from -5 degrees to -7 degrees or -9 degrees C reduced follicle
      survival rates from 49 +/- 4% to 26 +/- 1% and 28 +/- 3% respectively. If thawing
      was carried out at 27 degrees C follicle survival rate was higher (38 +/- 7%)
      than at 37 degrees C (26 +/- 2%) or 47 degrees C (20 +/- 6%). Follicles surviving
      8 days of in-vitro culture were stimulated with human chorionic gonadotrophin.
      The number of mature oocytes released did not differ between any experimental
      group. The results indicate that follicles isolated from frozen-thawed tissue can
      be grown to antral sizes and produce mature oocytes. The in-vitro culture system
      also proved a sensitive method for testing variations in the freeze-thaw
      protocol.

PMID- 11228207
TI  - Effect of feeding on growth hormone response to growth hormone-releasing hormone
      in polycystic ovarian syndrome: relation with body weight and hyperinsulinism.
AB  - The plasma growth hormone (GH) response to direct stimulation with growth hormone
      releasing hormone (GHRH) before and after a standard meal was investigated in 14
      polycystic ovarian syndrome (PCOS) subjects. Data were compared with those
      obtained from 14 healthy normovulatory matched patients. All women underwent an
      oral glucose tolerance test (OGTT) (75 g) and basal plasma hormone concentrations
      were evaluated. On a different day all subjects had a GHRH test (50 microg GHRH)
      both before and after lunch randomly. In obese PCOS subjects the GH response to
      GHRH was blunted after a meal, while in obese control patients there was an
      enhanced response of GH to GHRH after a meal. Normal control subjects showed an
      inhibition of the GH response after feeding and lean PCOS subjects showed a trend
      toward an augmented GHRH related secretion after a meal significantly higher than
      normal controls (P < 0.05) but not significantly higher than the pre-prandial
      response. In conclusion, the data indicate in PCOS a derangement of GH secretion
      related to food ingestion; in particular obese PCOS patients did not exhibit any
      change of GH response after a meal compared with the paradoxical response
      observed in obese controls. Several other factors beyond body mass index and
      hyperinsulinism could be involved in these pathophysiological events.

PMID- 11228208
TI  - Morphometric analysis of peri-implantation endometrium in patients having
      excessively high oestradiol concentrations after ovarian stimulation.
AB  - The present study investigated whether high oestradiol concentrations after
      ovarian stimulation in infertile women affect endometrial development around the
      time of implantation. The glandular and stromal components of the endometrium
      were assessed by morphometric criteria. Endometrial biopsies were taken on day 7
      (+/-1) after the ovulating dose of human chorionic gonadotrophin in stimulation
      cycles and on day 7 after the LH surge in natural cycles. Women (n = 38)
      undergoing assisted reproduction treatment were evaluated: 12 women in natural
      cycles, 11 women in stimulation cycles with oestradiol <20,000 pmol/l and failed
      fertilization after oocyte collection (moderate responders) and 15 women with an
      oestradiol concentration of > or =20,000 pmol/l in stimulation cycles (high
      responders). High responders showed delayed glandular maturation and advanced
      stromal morphology, whereas moderate responders demonstrated synchronous
      development of glandular and stromal features. In natural cycles, the glands were
      in phase. The effect of excessively high oestradiol concentrations could be
      explained by quantitative evaluation of the endometrial biopsies as gland-
      stromal dyssynchrony, which indicates a deficient secretory transformation of the
      endometrium that represents a suboptimal endometrial environment for
      implantation. This substantiates our previous clinical observation of
      significantly lower pregnancy rates in IVF cycles of women with high oestradiol
      concentrations (> or =20,000 pmol/l).

PMID- 11228209
TI  - Physiological concentrations of albumin stimulate chorionic gonadotrophin and
      placental lactogen release from human term placental explants.
AB  - This study investigates whether albumin, a major plasma protein in direct contact
      with the trophoblast in vivo, can modulate human chorionic gonadotrophin (HCG)
      and human placental lactogen (HPL) releases from placental explants. Incubating
      explants with a near physiological, i.e. 5%, concentration of human or bovine
      albumin during 30 min increased HCG and HPL release by at least 150%. This
      albumin effect was not mediated by any difference in hormone adsorption onto
      glass surfaces. In contrast to the sustained stimulation of hormone releases
      elicited by the addition of 10 mmol/l extracellular calcium, the albumin-mediated
      secretory responses were transient. However, the albumin- and calcium-stimulatory
      effects were abolished at 4 degrees C, depressed by 0.36 mmol/l cycloheximide or
      1 mmol/l colchicine and potentiated by 40 micromol/l cytochalasin B. Moreover,
      the stimulatory effect of albumin on the hormone releases was not modified in the
      absence of Ca(2+) or in the presence of 1 or 10 mmol/l Ca(2+) in the
      extracellular milieu. These data suggest that albumin is involved, at
      physiological concentration, in the secretion of HCG and HPL by human placenta.
      The cellular mechanism(s) underlying the albumin-mediated secretory responses may
      be partly different from those involved during the calcium-mediated stimulation.

PMID- 11228210
TI  - Lipoprotein(a) changes during natural menstrual cycle and ovarian stimulation
      with recombinant and highly purified urinary FSH.
AB  - This prospective, randomized, controlled study compared the effects of
      recombinant human FSH (r-hFSH) and highly purified urinary FSH (u-hFSH HP) on
      lipoprotein(a) [Lp(a)] concentrations in women undergoing ovarian stimulation.
      Fifty infertile women were randomly allocated into two equally sized treatment
      groups (n = 25 per group). Thirty normal ovulation women were recruited as
      controls. The infertile women received u-hFSH or r-hFSH 150 IU/day starting on
      cycle day 2. From cycle day 6 the dose was adjusted according to ovarian
      response. Human chorionic gonadotrophin 10,000 IU was administered once there was
      at least one follicle > or =18 mm in diameter. The luteal phase was supported
      with progesterone 50 mg/day for at least 15 days. Repeated measurements of Lp(a)
      concentrations were performed during both stimulated and natural cycles. A
      significant increase in luteal phase Lp(a) concentrations was detected in the
      stimulated cycles, whereas no significant changes in serum Lp(a) concentrations
      were observed during natural cycles. There were no significant differences
      between the urinary and recombinant FSH effects on serum Lp(a). The luteal Lp(a)
      increase was transitory because after 1 month Lp(a) concentrations returned to
      baseline values if pregnancy failed to occur; in pregnant women persistent
      increased Lp(a) concentrations were found at the 8th week. The percentage changes
      in serum Lp(a) were positively correlated with the luteal progesterone increase
      (r = 0.40, P < 0.05), but not with follicular or luteal oestradiol increase. The
      women with low baseline Lp(a) (< or =5 mg/dl) had a greater increase of the Lp(a)
      concentrations at midluteal phase than women with baseline Lp(a) >5 mg/dl. In
      conclusion, the recombinant or urinary hFSH administration does not directly
      influence Lp(a) concentrations. The luteal Lp(a) increase in stimulated cycles is
      not related to gonadotrophin treatment per se, but appears to be related to the
      high luteal progesterone concentrations, physiologically or pharmacologically
      determined. Our results also suggest that the sensitivity to the progesterone
      changes could be related to apolipoprotein(a) phenotype.

PMID- 11228211
TI  - Increased serum FSH in female fragile X premutation carriers with either regular
      menstrual cycles or on oral contraceptives.
AB  - Fragile X premutations are known to be a risk factor for diminished ovarian
      function at a relatively young age. We studied endocrine profiles of female
      fragile X family members (n = 79) at risk of premature ovarian failure (POF). Of
      these 79 women aged <40 years, 45 had menstrual cycles, and 34 were using oral
      contraceptives. Of the women with menstrual cycles, the premutation carriers had
      higher serum FSH concentrations than women who were not carrying the premutation.
      Even premutation carriers with regular cycles showed increased serum FSH
      concentrations. Moreover, premutation carriers using oral contraceptives also
      demonstrated increased serum FSH concentrations. Irrespective of whether oral
      contraceptives were used, a serum FSH concentration of > or =15 IU/l was more
      common in the premutation carriers than in the other women. One premutation
      carrier using oral contraceptives had a serum FSH concentration of >40 IU/l, the
      threshold that defines POF. We confirmed that premutation carriers with menstrual
      cycles demonstrate premature ovarian dysfunction. However, we also found
      endocrine signs of unrecognized ovarian dysfunction in premutation carriers using
      oral contraceptives, despite endocrine alterations by oral contraceptives.
      Premutation carriers may have a poorer prognosis for future pregnancy, either
      achieved spontaneously or by assisted reproductive technology. We recommend that
      premutation carriers should be counselled not to wait too long if they wish to
      start a family.

PMID- 11228212
TI  - Increased adhesiveness and internalization of Neisseria gonorrhoeae and changes
      in the expression of epithelial gonococcal receptors in the Fallopian tube of
      copper T and Norplant users.
AB  - Interaction of Neisseria gonorrhoeae with the oviductal epithelium in vitro was
      examined in 2 cm length segments obtained after surgical sterilization from users
      of copper T intrauterine device (IUD) or Norplant and control women. Segments
      perfused with N.gonorrhoeae suspensions were incubated from 30 min up to 4 h,
      fixed, frozen and cut in 6--10 microm sections. Bacteria were detected
      immunohistochemically with rabbit anti-gonococcal serum followed by light and
      confocal microscopy. Adhesion and internalization of gonococci by epithelial
      cells were observed at all incubation times, and both were higher in explants
      from users of copper T IUD or Norplant implants than controls. The epithelium of
      controls expressed CD66 and syndecan-1; but CD46 was found in only one out of six
      cases. The epithelium of copper T IUD users expressed CD66 but not syndecan-1 or
      CD46. Users of Norplant exhibited expression of CD46, CD66 and syndecan-1. Label
      was always found along the luminal border of the epithelium. There were more
      intraepithelial lymphocytes in users of contraceptive methods than in controls.
      Results indicate that (i) N.gonorrhoeae invade the oviductal epithelium from the
      first minutes of exposure, (ii) the epithelium is constitutively endowed with two
      known receptors for the gonococcus, CD66 and syndecan-1, (iii) copper T IUD and
      Norplant users exhibit higher rates of attachment and internalization of the
      gonococcus into the oviductal epithelium associated with changes in expression of
      gonococcal receptors.

PMID- 11228213
TI  - Efficacy, tolerability and acceptability of a novel contraceptive vaginal ring
      releasing etonogestrel and ethinyl oestradiol.
AB  - A novel contraceptive vaginal ring releasing etonogestrel 120 microg and ethinyl
      oestradiol 15 microg daily over a period of 3 weeks was tested. Each ring was
      used for one cycle, comprising 3 weeks of ring use followed by a 1 week ring-free
      period. This 1 year, multicentre study assessed the contraceptive efficacy, cycle
      control, tolerability and acceptability of the contraceptive. Altogether, 1145
      women were exposed to the vaginal ring for 12,109 cycles (928 woman-years). Six
      pregnancies occurred during treatment, giving a Pearl Index of 0.65 (95%
      confidence interval 0.24--1.41). Cycle control was very good, since irregular
      bleeding was rare (2.6--6.4% of evaluable cycles) and withdrawal bleeding (mean
      duration 4.7--5.3 days) occurred in 97.9--99.4% of evaluable cycles. Compliance
      to the prescribed regimen was high with criteria being fulfilled in 90.8% of
      cycles. The ring was well tolerated. The majority of women considered this new
      contraceptive method easy to use, and it offers an effective, convenient, well
      accepted and novel method for hormonal contraception.

PMID- 11228215
TI  - Male infertility risk factors in a French military population.
AB  - We investigated infertility risk factors by conducting a population-based case
      control study in the military population of the French town of Brest. Sixty
      couples who had sought medical advice for infertility of more than 12 months
      duration (cases) were compared with 165 couples who had had a child (controls).
      All the men in these couples had been employed by the military. The infertility
      risk factors studied were male and female medical factors, occupational and
      environmental exposures. We obtained age-adjusted odds ratios of 7.4 [95%
      confidence interval (CI): 1.4--39.5] for testis surgery, and 13.0 for varicocele
      (95% CI: 1.4--120.3) in men. In logistic regression, the age-adjusted odds ratio
      for men who had worked in a nuclear submarine was found to be 2.0 (95% CI: 1.0-
      3.7), and that for heat exposure was 4.5 (95% CI: 1.9--10.6). One limitation of
      this study is the lack of exposure measurements, especially for potential
      exposure to nuclear radiation (type of reactor used in nuclear-powered
      submarines, inability to obtain personal dosimeters worn by military personnel
      working in nuclear submarines). In conclusion, this study suggests that in this
      military population, having worked as a submariner in a nuclear-powered
      submarine, and having worked in very hot conditions, should be considered as risk
      factors for infertility.

PMID- 11228214
TI  - A prospective, randomized study comparing day 2 and day 3 embryo transfer in
      human IVF.
AB  - It is believed that delayed transfer of embryos after IVF allows for a better
      selection of good quality embryos. Hence, the number of embryos and all other
      prognostic factors being equal, transfer of day 3 embryos should be associated
      with higher implantation and pregnancy rates than transfer of day 2 embryos. To
      investigate this hypothesis, a prospective randomized study was carried out to
      compare implantation and pregnancy rates between day 2 and day 3 transfers. The
      relationship between the embryo quality score of day 2 and day 3 embryos and
      their respective implantation rates was also analysed. In a 2 year period all
      patients undergoing infertility treatment and in whom at least seven normally
      fertilized oocytes were obtained were included in the study. A minimization
      procedure was performed taking into account the patient's age and the method of
      fertilization (IVF or intracytoplasmic sperm injection). By using a uniform
      policy of embryo transfer, the number of embryos transferred was similar in both
      groups. The outcome parameters were embryo quality, implantation and pregnancy
      rates. No difference was observed in implantation and pregnancy rates between
      transfers on day 2 versus day 3 (23.8 versus 23.8% and 47.9 versus 46.8%
      respectively). The incidence of embryos of moderate to poor quality was higher in
      embryos cultured for 3 days compared with those cultured for 2 days. It is
      concluded that the outcomes of embryo transfer in terms of implantation and
      pregnancy rates are comparable for day 2 and day 3 embryos, although the overall
      embryo quality score decreases when embryos are kept in culture till day 3.

PMID- 11228216
TI  - Chlamydia pneumoniae and screening for tubal factor subfertility.
AB  - Chlamydia antibody testing (CAT) by micro-immunofluorescence (MIF) tests has been
      introduced into the fertility work-up as a screening test for tubal factor
      subfertility. In this study the role of C. pneumoniae antibodies, as a cause for
      false positive CAT results due to cross-reactivity with C. trachomatis antibodies
      in the MIF test, has been evaluated. In 240 subfertile women serological data
      were compared to laparoscopy findings. The prevalence of C. pneumoniae antibodies
      using enzyme-linked immunosorbent assay (ELISA) was 75% and did not differ
      between patients with and without tubal pathology. C. pneumoniae antibodies were
      found in 87% of women with a positive MIF test (> or =32), and in 66% with a
      negative MIF test (P < 0.0005). Using ELISA instead of MIF for the detection of
      C. trachomatis antibodies, C. pneumoniae antibodies were found in 87% of C.
      trachomatis positive women, and in 69% of C. trachomatis negative women (P <
      0.0005). Patients without tubal factor subfertility but a positive MIF test
      showed C. pneumoniae antibodies more frequently than patients without tubal
      factor subfertility and a negative MIF test. Therefore it was suggested that C.
      pneumoniae antibodies may be the cause of false positive CAT results. Remarkably,
      tubal pathology was more common in patients who had antibodies to both C.
      trachomatis and C. pneumoniae.

PMID- 11228218
TI  - A comparison of ICSI outcomes with fresh and cryopreserved epididymal spermatozoa
      from the same couples.
AB  - The published experience with frozen-thawed epididymal spermatozoa and
      intracytoplasmic sperm injection (ICSI) suggests that fertilization and pregnancy
      success rates are comparable to those achieved with freshly retrieved
      spermatozoa. However, no study has exactly compared clinical outcomes between the
      two IVF/ICSI cycles in the same couples. To formally address this issue, we
      assessed ICSI outcomes in couples each of whom had had two IVF/ICSI cycles: one
      using fresh and the second using frozen-thawed epididymal spermatozoa obtained
      from a single aspiration procedure. From a pool of 101 consecutive patients
      undergoing IVF/ICSI with epididymal spermatozoa, 19 couples initially used fresh
      epididymal spermatozoa and subsequently underwent a second IVF/ICSI procedure
      with frozen-thawed spermatozoa from the same aspiration. Normal (2PN) oocyte
      fertilization rates, embryo quality and pregnancy rates were compared between the
      two IVF/ICSI cycles for each couple. In the fresh epididymal sperm group, 58.4%
      of the injected oocytes fertilized normally compared with 62.0% of the injected
      oocytes in the frozen-thawed epididymal sperm group, revealing no statistically
      significant difference. Graded embryo quality also did not differ significantly
      between the paired IVF/ICSI cycles. The clinical pregnancy rates were 31.6%
      (6/19) and 36.8% (7/19) in the first and second cycles respectively. All but one
      pregnancy were singletons. In summary, this study provides strong evidence to
      support the notion that motile, cryopreserved and thawed epididymal spermatozoa
      are equal to freshly retrieved spermatozoa for ICSI in couples with obstructive
      azoospermia.

PMID- 11228217
TI  - Dose-finding study for the use of long-acting gonadotrophin-releasing hormone
      analogues prior to ovarian stimulation for IVF.
AB  - Gonadotrophin-releasing hormone (GnRH) analogues improve the outcome of treatment
      with IVF by increasing the number and quality of oocytes retrieved and by
      reducing cycle cancellation rates. Whilst short-acting GnRH analogues are most
      commonly used, depot preparations are now available that are more convenient for
      patient use. Some studies have reported that pregnancy rates with depot GnRH
      analogues are similar to those of short-acting preparations, but others have
      suggested that the more profound down-regulation seen with depot GnRH analogues
      results in inferior embryo quality. The purpose of this study was to determine
      whether a lower than conventional dose of a depot GnRH analogue may be more
      appropriate for use in ovarian stimulation prior to IVF. Sixty patients were
      randomized to receive either 3.75 mg (conventional dose) or 1.87 mg (low dose)
      triptorelin prior to ovarian stimulation for IVF. Suppression was measured using
      serum concentrations of LH measured 2 and 3 weeks after the administration of the
      GnRH analogues, the dose of gonadotrophin used and the time to resumption of
      menses. Mean concentrations of LH were 2.2 +/- 1.0 and 1.1 +/- 0.6 IU/l in the
      conventional dose group and 3.5 +/- 5.5 and 2.7 +/- 1.9 IU/l in the low dose
      group (P < 0.05 at 2 and 3 weeks). There were no significant differences between
      the doses of gonadotrophins used, the number of oocytes and embryos available and
      the time to resumption of menses, nor in the pregnancy rates. Although the degree
      of suppression as measured biochemically was more profound with the conventional
      dose, this did not affect the IVF outcome. The use of a lower dose therefore
      appears to be equally effective and could contribute to a reduction in the cost
      of treatment.

PMID- 11228220
TI  - Congenital malformations in infants born after IVF: a population-based study.
AB  - The presence of congenital malformations in infants born after IVF was studied
      from a register consisting of practically all infants born in Sweden after IVF,
      1982--1997 (n = 9111). A further 64 infants were studied using only medical
      records. It is a nation-wide study and has a population-based control group (n =
      1,690,577) and relevant potential confounders have been taken into account. There
      was an excess of congenital malformations registered in the Medical Birth
      Registry (n = 516, odds ratio = 1.47) but this excess disappeared when
      confounders were taken into consideration: year of birth, maternal age, parity,
      and period of unwanted childlessness (odds ratio = 0.89). For some specific
      conditions, an approximately 3-fold excess risk was seen: neural tube defects,
      alimentary atresia, omphalocele, and hypospadias (after intracytoplasmatic sperm
      injection). No excess risk for hypospadias was seen after standard IVF. Various
      explanations for these findings are discussed. It is postulated that the excess
      risk for alimentary atresia, like the excess risk for monozygotic twinning after
      IVF, is a direct consequence of the IVF procedure. The excess risk for
      hypospadias after ICSI may be related to paternal subfertility with a genetic
      background. The absolute risk for a congenital malformation in association with
      IVF is small.

PMID- 11228219
TI  - Use of microdose GnRH agonist protocol in women with low ovarian volumes
      undergoing IVF.
AB  - Ovarian volume measurements have been recently shown to be predictive of response
      to ovarian stimulation. Women with small ovarian volumes, i.e. <3 cm(3), have a
      higher incidence of cycle cancellation, together with a lower peak oestradiol
      concentration, lower number of retrieved oocytes, and lower pregnancy rates,
      compared with women with larger ovarian volumes. We prospectively investigated
      whether a higher dose, microdose flare gonadotrophin-releasing hormone (GnRH)
      agonist protocol, can improve IVF outcome in women with a small ovarian volume.
      Only the first IVF cycle was reviewed. In total, 109 women aged <40 years
      undergoing 109 cycles were prospectively evaluated. Women with an ovarian volume
      of < or =3 cm(3) noted on the day of luteal GnRH agonist administration had their
      stimulation regimen changed to a more aggressive microdose flare GnRH agonist
      protocol. In all, 30 women (27.5%) with an ovarian volume of <3 cm(3), and 79
      women (72.5%) with an ovarian volume of >3 cm(3) were compared. Women with an
      ovarian volume of <3 cm(3) had a significantly higher incidence of unexplained
      infertility as their presenting aetiology, compared with women with a larger
      ovarian volume (33 and 8.6%, P = 0.0036). There was a significant negative
      correlation between age and ovarian volume, and between day 3 FSH concentration
      and ovarian volume. We also report a significant positive correlation between
      body mass index and ovarian volume. There was also a significant positive
      correlation between ovarian volume and the number of oocytes retrieved. Despite a
      trend towards higher day 3 FSH concentrations, a significantly longer duration of
      stimulation, higher gonadotrophin requirements, and lower oocyte yield, the
      implantation and pregnancy rates were comparable between the two groups. Women
      with a small ovarian volume noted at baseline ultrasound can have comparable
      implantation and pregnancy rates to those with larger ovarian volumes with the
      use of a higher dose gonadotrophin, microdose GnRH agonist stimulation.

PMID- 11228221
TI  - Internal jugular vein thrombosis after ovarian stimulation.
AB  - Thromboembolic events are serious, but fortunately rare, complications following
      ovarian stimulation for IVF. Here, we report a case of internal jugular vein
      thrombosis after ovarian stimulation with gonadotrophins. Most of the cases of
      thrombosis are late complications of ovarian hyperstimulation syndrome (OHSS) or
      hereditary hypercoagulability. Screening for these risk factors in our patient
      was negative. The patient was successfully treated with low molecular weight
      heparin and a twin pregnancy is ongoing.

PMID- 11228222
TI  - Mitochondria in human offspring derived from ooplasmic transplantation.
AB  - Ooplasmic transfer from fertile donor oocytes into potentially compromised
      recipient patient oocytes has led to the birth of nearly 30 babies worldwide.
      Cytoplasmic transplantation has caused apprehension, since the mixing of human
      ooplasm from two different maternal sources may generate mitochondrial (mt)
      heteroplasmy (both recipient and donor mtDNA) in offspring. This investigation
      traced the mitochondrial donor population both during the ooplasmic transfer
      technique and in the bloods of two 1 year old children using mtDNA
      fingerprinting. Donor ooplasm stained for active mitochondria was transferred
      into recipient ooplasm and the mitochondria were visualized by confocal
      microscopy after the microinjection procedure and fertilization. Heteroplasmy was
      found in the blood from each of the children. This report is the first case of
      human germline genetic modification resulting in normal healthy children.

PMID- 11228223
TI  - Relationship of seminal plasma interleukin (IL) -8 and IL-6 with semen quality.
AB  - The concentration of interleukin (IL) -8 and IL-6 was determined in seminal
      plasma (SP) samples from 137 randomly chosen subfertile males to evaluate the
      relationship with other potential parameters of subclinical
      infection/inflammation such as seminal leukocytes, and with semen quality in a
      prospective study. All patients were asymptomatic for genital tract infection. A
      comprehensive semen evaluation included sperm analysis, sperm migration testing,
      antisperm antibody screening, immunocytochemical round cell differentiation to
      determine seminal leukocytes counts and the leukocyte ratio, complement fraction
      C(3) (C(3c)) determination, and semen cultures, in aliquots of the same
      ejaculates. The SP concentration of IL-8 was inversely related to semen quality,
      e.g. to the total number of motile spermatozoa or to the outcome of the sperm
      migration test (motile sperm harvested after a swim-up procedure). IL-8
      concentrations were significantly correlated with leukocyte counts per ml (P <
      0.0001) and per ejaculate (P < 0.0001), and with the leukocyte ratio (P < 0.001).
      All leukocytospermic samples had high IL-8 concentrations (< or =2 ng/ml). The SP
      concentration of IL-6 was much lower, but was significantly correlated with IL-8
      (P < 0.0001). Both IL-8 and IL-6 were significantly related with the C(3c). No
      association of interleukin concentrations with the bacterial colonization of
      semen samples was found. The results indicate a marked relationship of some pro
      inflammatory cytokines with semen quality. The significant association with
      seminal leukocytes and other potential inflammation markers suggests that IL-8
      might be used as sensitive marker for silent male genital tract infection.

PMID- 11228224
TI  - Impaired spermatogenesis in men with congenital absence of the vas deferens.
AB  - It is generally assumed that men with congenital bilateral absence of the vas
      deferens (CBAVD) have azoospermia because of obstruction and that sperm
      production is normal. This study examines spermatogenesis in men with CBAVD to
      assess the validity of this assumption. We identified all men with CBAVD who had
      undergone either a diagnostic or therapeutic fertility procedure. Procedures
      included diagnostic biopsy, testis fine needle aspiration (FNA) mapping,
      microscopic epididymal sperm aspiration (MESA), and testis sperm extraction
      (TESE). Among 33 CBAVD men, 18 underwent testis biopsy, 27 had MESA/TESE, and 10
      had FNA mapping. On evaluation of these procedures, normal spermatogenesis was
      present in 29 men. Four men (12%) demonstrated impaired spermatogenesis. One
      patient had FNA testis cytology consistent with late maturation arrest, another
      demonstrated hypospermatogenesis on biopsy and low sperm yield by MESA, and two
      patients had pure Sertoli cell only histology on biopsy. Aetiologies for impaired
      spermatogenesis included varicocele and underlying genetic abnormalities.
      Although patients with CBAVD are assumed to have normal spermatogenesis and
      infertility due simply to obstruction, the potential for concomitant defects in
      sperm production exists. A clinical suspicion of testis failure should prompt
      further diagnostic evaluation of spermatogenesis prior to sperm retrieval. In
      addition, genetic counselling should be offered and testing for genetic lesions,
      including cystic fibrosis gene mutations and/or variants, Y chromosome
      microdeletions, and karyotype abnormalities, should be considered.

PMID- 11228225
TI  - Chromatin status in human ejaculated spermatozoa from infertile patients and
      relationship to seminal parameters.
AB  - The aim of this study was to evaluate the chromatin status in different groups of
      patients. Five groups of men were selected: pre-vasectomy; male factor
      infertility; varicocele; immunological male infertility; and idiopathic
      infertility. Chromatin status was evaluated using flow cytometry after staining
      the DNA with the fluorochrome propidium iodide. Differences were observed in the
      state of sperm chromatin between the male factor and varicocele groups with
      respect to the others. These two groups presented poorer quality chromatin, as
      evidenced fundamentally by a lower degree of condensation. These deficiencies in
      chromatin status were usually accompanied by alterations in the other standard
      parameters of semen analysis. Individuals who are infertile due to male factor
      and those presenting varicocele have spermatozoa with less condensed chromatin
      which might, in part, explain their sterility.

PMID- 11228226
TI  - Ultrastructural observations of enzymatically treated human blastocysts: zona
      free blastocyst transfer and rescue of blastocysts with hatching difficulties.
AB  - Enzymatic treatment of the zona pellucida to either soften or remove totally the
      zona before blastocyst transfer has resulted in high implantation rates. The zona
      is usually completely dissolved after 1.5 min exposure with 10 IU pronase at 37
      degrees C. Since there may be concerns that pronase treatment for periods of 1.5
      min or longer may cause adverse effects on the trophectoderm (TE) and inner cell
      mass (ICM), the changes to human blastocysts exposed to different time intervals
      of pronase were investigated. Of 18 blastocysts exposed to pronase for 1.5 min,
      the zona was completely dissolved and no changes were observed by light
      microscopy (LM) or transmission electron microscopy (TEM), compared with 11
      naturally hatched untreated blastocysts (controls). In another five blastocysts
      exposed to pronase for 2 min, no LM changes were observed but subtle TEM changes
      such as fewer bundles of tonofibrils attached to desmosomes were observed. When
      three other blastocysts were exposed to pronase for 5 min, the blastocoele
      collapsed, and the TE cells started to show blebbing under LM. Under TEM, the
      cytoplasm of TE cells was extensively vacuolated and many TE cells showed
      cytoplasmic blebbing towards the blastocoele. However, the epithelium was
      uninterrupted with intact tight junctions and desmosomes. Of a separate group of
      44 blastocysts cultured in vitro, 54.5% had hatching difficulties when monitored
      from day 5 to day 8 and 80% of these could be rescued by removal of the zona with
      pronase for 1.5 min prior to extensive degeneration taking place. The results
      confirm that the optimal time for softening or complete removal of the zona
      before transfer was around 1.5 min and that enzymatic treatment was a safe, non
      invasive procedure to remove the zona of blastocysts. The human embryonic TE is a
      very hardy, robust epithelium that withstands pronase treatment.

PMID- 11228227
TI  - The effects of meiosis activating sterol on in-vitro maturation and fertilization
      of human oocytes from stimulated and unstimulated ovaries.
AB  - The object of this study was to assess functional maturation in vitro by
      obtaining data on the fertilization and embryonic competence of human oocytes
      with or without exposure to meiosis activating sterol (MAS) during maturation in
      vitro. Immature oocytes were either collected from unstimulated patients with
      polycystic ovaries (PCO) during gynaecological surgery, or were donated by
      patients undergoing a cycle of intracytoplasmic sperm injection (ICSI) treatment
      including ovarian stimulation with gonadotrophins. PCO oocytes had variable
      cumulus cover, which was retained during culture while those from ICSI patients
      were cultured without cumulus. The study included 119 oocytes from PCO patients
      and 72 from ICSI patients. The oocytes were allowed to mature in vitro for up to
      46 h in the presence or absence of MAS. Mature oocytes were inseminated by ICSI
      with fertile donor spermatozoa and embryo development was monitored in vitro. MAS
      (30 microg/ml) significantly increased the survival of oocytes from PCO patients
      (P < 0.01) but did not significantly affect the proportion completing maturation
      in vitro. For the ICSI patients, >90% of oocytes survived in all culture groups,
      regardless of MAS addition, however MAS (10 or 30 microg/ml) significantly
      increased the proportion of oocytes maturing in vitro (P < 0.05). The apparent
      tendency towards improved subsequent development in vitro will require larger
      numbers of oocytes for evaluation. Oocytes from ICSI patients matured more
      rapidly in vitro than those from PCO patients. Our results show positive effects
      of MAS on human oocytes, confirming previous data in mice. This work may have
      implications for the future clinical application of IVM.

PMID- 11228228
TI  - Prevalence of diabetes mellitus, hypertension and cardiac complaints in a follow
      up study of a Dutch PCOS population.
AB  - The aim of this study was to investigate the prevalence of diabetes mellitus,
      hypertension and cardiac complaints in a Dutch population with polycystic ovarian
      syndrome (PCOS) and to compare the results with the prevalence of these
      conditions in the Dutch female population, as retrieved from the Netherlands
      Health Interview Survey of Statistics Netherlands. A total of 346 PCOS patients
      were interviewed by telephone, with a mean age of 38.7 years (range 30.3--55.7)
      and a mean body mass index of 24.4 (range 17.5--55.8). Diabetes occurred in eight
      (2.3%), hypertension in 31 (9%) and cardiac complaints in three (0.9%) of the
      women. The prevalence of diabetes and hypertension differed significantly from
      the prevalence of these conditions in the Dutch female population (both P <
      0.05). In PCOS women aged 45--54 years (n = 32) the prevalence of diabetes was
      four times higher (P < 0.05) and of hypertension 2.5 times higher (P < 0.01) than
      the prevalence of these conditions in the corresponding age group of the Dutch
      female population. Hypertension also occurred significantly (P < 0.05) more in
      the younger (35--44 years) PCOS group (n = 233), but this age group was
      significantly more obese (P < 0.01) when compared with figures of obesity of the
      Dutch female population. In conclusion, our data show that in a follow-up study
      of a relatively lean PCOS population, the prevalence of diabetes mellitus and
      hypertension was increased when compared with the Dutch female population,
      especially in women aged 45--54 years.

PMID- 11228229
TI  - Distribution of cyclooxygenase-2 in eutopic and ectopic endometrium in
      endometriosis and adenomyosis.
AB  - The objective of this study was to determine the distribution of cyclooxygenase-2
      (COX-2) in eutopic and ectopic endometria in endometriosis and adenomyosis. The
      subjects were 35 patients with endometriosis diagnosed by laparoscopy, 33
      patients with histologically confirmed adenomyosis and 50 female controls with
      normal fecundity. Expression of COX-2 was immunohistochemically investigated in
      tissues from eutopic endometrium and myometrium and ectopic endometrium of the
      wall of ovarian chocolate cysts using polyclonal antibody. Surface epithelial
      cells, endometrial glandular epithelial cells or stromal cells were assessed.
      Cells were semi-quantitatively assessed on a scale of 1 to 5 using a nomogram
      created from positive cell count and the degree of staining. COX-2 expression in
      surface and glandular epithelia of the control group varied markedly during the
      menstrual cycle. It was lowest in the early proliferative phase and gradually
      increased thereafter. It remained high throughout the secretory phase. However,
      in patients with endometriosis, expression of COX-2 in glandular epithelium was
      higher than that in the control group, though it varied throughout the menstrual
      cycle. On the other hand, there was no variation in expression of COX-2 in the
      adenomyosis group during the menstrual cycle, and it was lower than that in the
      endometriosis group in all phases. Pronounced COX-2 expression was observed in
      glandular cells from ectopic endometrial tissue of ovarian chocolate cyst walls
      in all cases regardless of the menstrual phase. In summary, increased COX-2
      expression in eutopic and ectopic endometria was believed to be strongly
      correlated with pathological abnormalities in these disorders.

PMID- 11228230
TI  - Iron metabolism in monochorionic twin pregnancies in relation to twin--twin
      transfusion syndrome.
AB  - Fetal iron metabolism was investigated in monochorionic (MC) twin pregnancies in
      relation to twin-twin transfusion syndrome (TTTS). Matched maternal and fetal
      blood samples were obtained both in utero and at birth from MC twins with TTTS (n
      = 23) and without TTTS (n = 18). In a second group of 30 twin pairs (15 with and
      15 without TTTS), liver iron content was assessed by using archived paraffin wax
      embedded blocks. Serum ferritin was determined by radioimmunoassay and values are
      given as gestation independent Z-scores and expressed as mean with 95% confidence
      intervals. Ferritin concentrations in the recipients were higher than in the
      donors both in utero (P < 0.01) and at birth (P < 0.01). Fetal serum ferritin in
      non-TTTS twins were similar to the recipient twins but higher than the donor
      twins (P < 0.05). A significant association was found between ferritin
      concentrations, the total red blood cell count and haemoglobin in the TTTS twin
      pairs (P < 0.01) and the non-TTTS twins as a group (P < 0.01). The total
      stainable liver iron was comparable between twin pairs in the TTTS and non-TTTS
      groups. This study fails to provide evidence of iron overload in the recipient
      and depletion in the donor twins and, thereby, questions the validity of the
      conventional theory of inter-twin transfusion as the cause of TTTS.

PMID- 11228231
TI  - Erythropoietin in monochorionic twin pregnancies in relation to twin--twin
      transfusion syndrome.
AB  - Fetal erythropoietin (Epo) concentrations were studied in monochorionic (MC) twin
      pregnancies in relation to twin-twin transfusion syndrome (TTTS). Matched
      maternal and fetal blood samples in utero were obtained from MC twins with TTTS
      (n = 15) and without TTTS (n = 6). In a second group of five sets of twin pairs
      with or without TTTS, immunolocalization of Epo was performed in archived
      paraffin wax sections of liver and kidney collected at autopsy. Epo was measured
      using a chemiluminescence assay and expressed as gestation independent Z-scores
      and given as mean +/- 95% confidence intervals (CI). Fetal Epo concentrations in
      utero were higher in MC twins with TTTS than the non-TTTS as a group (P < 0.001).
      There was no difference in Epo concentrations between TTTS and non-TTTS twin
      pairs. Fetal Epo concentrations were correlated with pO(2) in the recipient (r =
      0.64; P < 0.01), donor (r = 0.64; P < 0.01) and control twins (r = 0.76; P <
      0.01). Immunostaining of the fetal kidney localized Epo primarily to the
      cytoplasm of the proximal convoluted tubules. The intensity of staining in the
      kidney and liver was comparable between TTTS and non-TTTS twin pairs. Fetal Epo
      concentrations were higher in the TTTS than non-TTTS twin pairs and were
      correlated with the degree of hypoxaemia. However, Epo concentrations were
      comparable between donor and recipient twins, perhaps due to similar production
      rather than inter-twin transfusion of blood.

PMID- 11228232
TI  - Induction of lactation in the intended mother of a surrogate pregnancy: case
      report.
AB  - A case of a successful induction of lactation in a commissioning mother of a
      surrogate pregnancy is reported. Induction of lactation was achieved with oral
      metoclopramide which was well tolerated. Alternative methods to induce lactation
      are reviewed. The advantages of breast-feeding and the relative ease with which
      lactation can be induced after a surrogate pregnancy would suggest that this
      could be offered to all commissioning mothers.

PMID- 11228233
TI  - Cervical ectopic twin pregnancy: diagnosis and conservative treatment: case
      report.
AB  - A case of cervical ectopic twin pregnancy with cardiac activity in both embryos
      is presented. It was diagnosed in the eighth week of gestation by
      ultrasonography, and treated conservatively with intra-amniotic administration of
      methotrexate under ultrasonographic guidance followed by curettage. This
      procedure allows subsequent gestations.

PMID- 11228234
TI  - Alexithymia in male infertility.
AB  - The continuing confrontation with the thoughts and feelings surrounding an
      unfulfilled wish for a child makes coping very difficult. There is empirical
      evidence that, in medical illnesses associated with stress and loss of quality of
      life, patients react with alexithymia, which means a difficulty to communicate
      emotions. In this study we compared 84 infertile men with a group of 96 healthy
      men and 43 male psychosomatic outpatients concerning their ability to communicate
      feelings, measured by the Twenty-Item Toronto Alexithymia Scale and the amount of
      psychopathologically relevant symptoms, especially somatization, measured by the
      Symptom Checklist 90-R and a List of Complaints (Beschwerden-Liste). The results
      showed a significantly higher alexithymia in infertile men compared with healthy
      men (P < 0.05), but a significantly lower alexithymia compared with psychosomatic
      outpatients (P < 0.05). Furthermore the study group showed significantly more
      somatic complaints in the List of Complaints compared with healthy men (P <
      0.05). The importance of alexithymia in male infertility is discussed on the
      basis of empirical results that it might play a defensive role as far as
      depression is concerned but on the other hand increases the possibility of
      somatic complaints. The need for prospective studies in further research is
      emphasized.

PMID- 11228236
TI  - The SCID mouse, experimental endometriosis and adhesions.

PMID- 11228235
TI  - Meta analysis on rFSH versus uFSH.

PMID- 11228237
TI  - Should we explore OHSS full clinical scope?...

PMID- 11228238
TI  - The causes of the variation of the probability of a son within couples.

PMID- 11228240
TI  - Cloning and characterization of human haspin gene encoding haploid germ cell
      specific nuclear protein kinase.
AB  - We report here the molecular cloning and characterization of human haspin cDNA
      and its genomic DNA construct. The haspin protein is a unique protein kinase,
      first isolated from mouse testis. Specifically expressed in mouse testicular germ
      cells, haspin is suggested to play a role in cell cycle arrest in haploid
      spermatids. Detection of human haspin by Northern blot analysis showed that the
      major transcript was 2.8 kilobases long and detected exclusively in the testis.
      The entire coding region of the human cDNA showed 68% identity with mouse haspin.
      The predicted amino acid sequence showed strong conservation of the kinase
      catalytic domain, leucine zipper, potential phosphorylation sites, and MEF2B
      homologous region, but a relatively unique N:-terminal region. Human haspin
      protein was also demonstrated to have protein kinase activity. The human haspin
      gene was mapped to chromosome 17p13 by computer database cloning of human genomic
      DNA. Furthermore, the genomic structure of human haspin was proven to be
      intronless and the whole transcription unit was found to be located in an intron
      of the integrin alphaE2 gene.

PMID- 11228241
TI  - Expression of the TAR RNA binding protein in human testis.
AB  - In testis, several RNA binding proteins have been shown to play a role in the
      translational regulation of specific transcripts. The human protein TRBP (TAR RNA
      binding protein) is the homologue of the mouse Prbp (Prm-1 RNA binding protein)
      involved in the protamine mRNA translational delay. TRBP is known to activate the
      HIV-1 long terminal repeat but this protein has never been investigated during
      spermatogenesis. The aim of this work was to analyse the TRBP expression in human
      testis. By Northern blot analysis, we demonstrated a major 1.5 kb transcript
      present at a high level in human testis and, to a lesser extent, in some other
      tissues. In-situ hybridization revealed that this transcript was present only in
      elongating spermatids. Antibodies raised against a 27 amino acid TRBP-specific
      peptide revealed a single protein of 43 kDa expressed in the cytoplasm of
      elongated spermatids. At the ultrastructural level, quantitative analysis of both
      TRBP mRNA and protein, using electron microscopy in-situ hybridization and
      immunocytochemistry, showed that TRBP is expressed mainly in spermatids at steps
      3-4 of spermiogenesis. These results are in agreement with the probable role of
      TRBP in the control of human protamine mRNA translation.

PMID- 11228242
TI  - Differential expression of oestrogen receptor alpha and beta proteins in the
      testes and male reproductive system of human and non-human primates.
AB  - The role(s) oestrogens play in male adult reproductive function remains
      uncertain. We have used antibodies specific for oestrogen receptor- alpha
      (ERalpha) and - beta (ERbeta) to investigate their distribution within the male.
      In testes from adult human, macaque and marmoset, ERbeta protein was detected in
      Sertoli cells, Leydig cells and peritubular myoid cells. In germ cells, the
      intensity of immunostaining for ERbeta was variable between species.
      Immunoexpression in preleptotene, leptotene and zygotene spermatocytes was
      low/absent in all species. Elongated spermatids were consistently immunonegative.
      No ERalpha immunoexpression was detected in testes. ERbeta was detected in
      epithelial and stromal cell nuclei throughout the male reproductive system
      [efferent ductules (ED), epididymis, vas deferens, seminal vesicles] and in the
      bladder. ERalpha was detected in non-ciliated epithelial cells in the ED, but
      rarely in epithelial and basal cells within the epididymis. Epithelial cells from
      seminal vesicles and bladder were immunonegative for ERalpha. Expression of
      ERalpha in stromal cells was rare in the ED, epididymis and bladder but more
      frequent in seminal vesicles. Expression of ERalpha, and long and short forms of
      ERbeta, was confirmed by Western blotting. The widespread expression of ERbeta
      suggests that it is the primary target for modulation of tissue function via
      oestrogenic ligands in the male reproductive system.

PMID- 11228243
TI  - A critical investigation of NADPH oxidase activity in human spermatozoa.
AB  - It has been suggested that human spermatozoa contain an NADPH oxidase that could
      generate reactive oxygen species involved in signalling pathways to promote
      fertility. The proposal depends on observations that the addition of NADPH to
      purified human spermatozoa stimulates chemiluminescence by the superoxide (O2-)
      probe, lucigenin. We confirmed these observations, but demonstrated that
      lucigenin increases NADPH consumption by spermatozoa and stimulates artefactual
      O2- production via a diphenyleneiodonium (DPI) sensitive flavoprotein. In the
      absence of cytochrome c, DPI-inhibitable NADPH oxidation by permeabilized
      spermatozoa was 8 times too small to account for the rate of NADPH-stimulated
      cytochrome c reduction. Thus NADPH can directly reduce cytochrome c by a
      flavoprotein dependent mechanism making this O2- assay also unreliable in sperm
      suspensions. We were unable to observe O2- production by 40 x 10(6)
      spermatozoa/ml using electron paramagnetic resonance spectroscopy but could
      identify O(2)(-) generation from 2000 4beta-phorbol-12-myristate-13-actetate
      (PMA)-stimulated leukocytes. Using spectrophotometry, we did not detect the
      reduced cytochrome b(558) component of the neutrophil NADPH oxidase in human
      spermatozoa. No hydrogen peroxide generation was observed using a sensitive
      Amplex Red assay. We conclude that human spermatozoa do not possess significant
      NADPH oxidase activity and that the mechanism by which NADPH promotes
      capacitation must be re-evaluated.

PMID- 11228244
TI  - Calcitonin, angiotensin II and FPP significantly modulate mouse sperm function.
AB  - Fertilization-promoting peptide (FPP) regulates the adenylyl cyclase (AC)/cAMP
      pathway to elicit capacitation-dependent responses, stimulating capacitation in
      uncapacitated spermatozoa and then arresting it in capacitated cells, thereby
      inhibiting spontaneous acrosome reactions. Like FPP, calcitonin and angiotensin
      II are found in seminal plasma and so might affect sperm function; this study
      investigated responses in uncapacitated and capacitated mouse spermatozoa to
      these three peptides. Both calcitonin (5 ng/ml) and angiotensin II (1 and
      10nmol/l), like FPP (100nmol/l), significantly stimulated capacitation, assessed
      using chlortetracycline (CTC) fluorescence and fertilization in vitro analyses.
      Combinations of two or three peptides, at high and low, non-stimulatory
      concentrations, were more stimulatory than the individual peptides, suggesting
      that they may act on the same signalling pathway, plausibly AC/cAMP; preliminary
      data indicate that calcitonin does stimulate cAMP production. In capacitated
      cells, FPP and calcitonin elicited pertussis toxin-sensitive inhibition of
      spontaneous acrosome loss, suggesting involvement of inhibitory G proteins;
      angiotensin II had no detectable effect. When all three peptides were used,
      angiotensin II did not interfere with inhibitory responses to FPP/calcitonin.
      These results suggest that angiotensin II, calcitonin and FPP may somehow
      modulate the AC/cAMP signal transduction pathway, but the precise mechanisms
      involved have yet to be elucidated.

PMID- 11228245
TI  - Vascular endothelial growth factor transgenic mice exhibit reduced male fertility
      and placental rejection.
AB  - Recent evidence points to the involvement of vascular endothelial growth factor
      (VEGF) in mammalian reproductive physiology. Transgenic mice expressing VEGF (121
      isoform) under the control of the polyepithelial mucin-1 (muc-1) promoter showed
      a reduction in male fertility due to impaired spermiogenesis, and aberrant
      placentation leading to preferential rejection of male embryos. A skew in the sex
      ratio of the litters was seen (three females to two males), independently of
      whether the transgene was carried by the male or female parent. In-situ
      hybridization permitted distinction of expression of the human VEGF transgene
      from endogenous mouse VEGF, and confirmed expression of the transgene in a wide
      range of epithelial tissues. Expression of the transgene in spermatocytes and in
      the embryonic portion of placenta is thought to be responsible for the reduced
      fertility and embryonic resorptions respectively. Males showed either complete
      sperm maturation arrest or various gradations of partial fertility. Abnormally
      high or low VEGF in human semen has been reported to be correlated with a lack of
      pregnancy success following IVF. The muc1-VEGF (121 isoform) transgenic mouse
      provides an animal model with which to further study this VEGF-induced pathology.

PMID- 11228246
TI  - Effects of interleukin-4 on the in-vitro production of cytokines by human
      endometrial stromal cells.
AB  - A T helper (Th)1/Th2 model has been applied to as a system regulating the
      cytokine network during pregnancy. To evaluate the effects of interleukin (IL)-4,
      a Th2 cytokine, on the cytokine production by endometrial stromal cells (ESC), an
      enzyme-linked immunosorbent assay was used to measure the concentrations of IL-6,
      IL-8, monocyte chemoattractant protein-1 (MCP-1), and macrophage colony
      stimulating factor (M-CSF) in the culture media of ESC and of an endometrial
      stromal sarcoma cell line, MaMi, following the addition of recombinant human IL
      4. The expression of mRNAs for IL-6 and IL-8 in ESC after stimulation with IL-4
      was also evaluated by Northern blot analysis. Increases in the concentrations of
      IL-6, IL-8, MCP-1, and M-CSF in the culture media of ESC and MaMi cells were
      observed on the addition of increasing amounts of IL-4. This cytokine also
      stimulated the transcription of IL-6 and IL-8 in ESC in a dose-dependent manner.
      It is suggested that IL-4 secreted by the maternal decidual tissue as well as by
      the developing embryo may stimulate the production of IL-6, IL-8, MCP-1, and M
      CSF by ESC. The increased concentration of these cytokines in the local
      environment may contribute to the maintenance of early pregnancy by modulating
      the immune reaction at the feto-maternal interface.

PMID- 11228247
TI  - Membrane-type 1 matrix metalloproteinase is induced in decidual stroma without
      direct invasion by trophoblasts.
AB  - Membrane-type 1 matrix metalloproteinase (MT1-MMP) in endometrium and decidua may
      greatly affect attachment of the embryo to the epithelium, invasion of the
      trophoblast into the stroma, and extracellular matrix remodelling in the
      endometrium and decidua. We investigated the expression of this enzyme in
      normally cycling endometrium and in decidua associated with normal and tubal
      pregnancies at both the gene and protein level. Localization of expression (but
      not the overall level of expression), differed between endometrium and decidua
      parietalis and tubal pregnancy decidua. MT1-MMP mRNA was expressed mainly in
      epithelium and only faintly in stroma throughout the menstrual cycle, while in
      decidua parietalis and tubal pregnancy decidua, this mRNA was expressed
      predominantly in stromal cells. MT1-MMP protein was detected in the epithelium
      alone throughout the menstrual cycle, while in decidua parietalis and tubal
      pregnancy decidua, it was detected in stromal cells as well as the epithelium.
      Since decidua showed altered expression in the absence of trophoblastic contact,
      trophoblast invasion may not directly affect MT1-MMP gene expression.

PMID- 11228248
TI  - Expression of ZO-1 and occludin in normal human placenta and in hydatidiform
      moles.
AB  - Zonula occludens-1 (ZO-1) and occludin are key molecules in cell-cell contacts.
      They are tight junction constituents and therefore play a pivotal role in tissue
      differentiation and organogenesis. In the present report we have investigated the
      expression of ZO-1 and occludin in normal human placentae and in hydatidiform
      moles using immunohistochemical and Western blot analyses. In normal placentae,
      ZO-1 and occludin were mainly localized in the apical part of the syncytium, in
      cell-cell contacts between syncytium and villous cytotrophoblastic cells as well
      as between the latter. Extravillous cytotrophoblast of cell islands and cell
      columns was positive for ZO-1 and occludin in the cell layers proximally located
      to the villous stroma whereas the cytotrophoblastic cells, distally located from
      the villous stroma, were totally negative. Furthermore, fetal vessels showed a
      positive staining pattern for ZO-1 throughout gestation, whereas a positive
      reaction for occludin was produced mainly at term. A striking result was the
      altered expression of ZO-1 and occludin in partial and complete moles. In 11
      moles, these two molecules were not expressed at all, while in the other nine,
      their expression was only cytoplasmic in syncytium and villous cytotrophoblastic
      cells. These findings suggest that ZO-1 and occludin participate in normal
      placental development, maintaining the organization and functions of different
      tissue components. The down-regulation and/or dysregulation of these two
      molecules may be related to phenotypic changes associated with epithelial cell
      transformation of the chorionic villi in partial and complete moles.

PMID- 11228249
TI  - Expression of insulin-like growth factor-I and placental growth hormone mRNA in
      placentae: a comparison between normal and intrauterine growth retardation
      pregnancies.
AB  - Intrauterine growth restriction (IUGR) is generally defined as the pathological
      restriction of fetal growth resulting in a fetus with birth weight below the 10th
      percentile for gestational age. Almost 75% of IUGR cases develop during third
      trimester. Studies on animals (rodents and sheep) as well as humans suggest that
      insulin-like growth factor-I (IGF-I), under the influence of placental growth
      hormone (PGH) plays crucial roles in fetal growth regulation during this period.
      Limited data are available with regard to IGF-I and PGH in placentae of normal
      and IUGR births. Therefore, in the present study, IGF-I and PGH mRNA expression
      has been studied in term placentae of normal (n = 10) and IUGR (n = 15) births by
      in-situ hybridization procedure. Their expression was also studied in first (n =
      5) and second (n = 5) trimester placentae obtained from elective termination of
      normal pregnancies. Both IGF-I and PGH expression were found to be higher in the
      first and second trimester placentae compared to term placentae in normal
      pregnancies. However, IUGR term placentae showed increased expression of both IGF
      I and PGH mRNA in comparison with normal placentae. Various mechanisms leading to
      the increased transcription of IGF-I and PGH mRNA in IUGR placenta are discussed.
      This increased transcription perhaps occurs in response to the reduction in the
      fetal growth.

PMID- 11228250
TI  - Different regulation of oestrogen receptors alpha and beta in the human cervix at
      term pregnancy.
AB  - During pregnancy, a cervical connective tissue remodelling takes place,
      clinically recognized as softening, effacement and dilatation. The role of
      oestrogens and their receptors (ER) in this process is not clear. ERalpha is a
      ligand-activated transcription factor involved in many physiological processes.
      The identification of a second oestrogen receptor, ERbeta, has led to a re
      evaluation of oestrogen signalling and physiology. The aim of this study was to
      monitor the expression of the two ERs in the cervix from women at term pregnancy
      (TP) and after parturition (PP) compared with that of non-pregnant (NP). A
      solution hybridization assay showed that the level of ERalpha mRNA was
      significantly decreased in the PP group, when compared with the NP and TP groups.
      In contrast the ERbeta mRNA level was increased in the TP group compared with the
      NP and PP groups. These results were supported by reverse transcription
      polymerase chain reaction (RT-PCR). Similar results were observed for the protein
      with immunohistochemistry. Intense ERbeta immunostaining was observed in
      neutrophils and the endothelial cells of blood vessels. In conclusion, this study
      supports a concept according to which oestrogen might be involved in the final
      remodelling of the cervix via the modulating effects of the two ERs. Furthermore,
      oestrogen may mediate some effects on cervical ripening via ERbeta present in the
      invading neutrophils. Further studies are needed to elucidate this finding.

PMID- 11228251
TI  - Quantification of the common deletion in human testicular mitochondrial DNA by
      competitive PCR assay using a chimaeric competitor.
AB  - The "common" 4977 bp deletion in mitochondrial DNA (Delta4977) is commonly used
      as an indicator of tissue deterioration in ageing and bioenergetic diseases.
      Deletion levels are normally measured by a serial dilution polymerase chain
      reaction (PCR) approach, where test reactions are compared with dilutions of
      control amplifications of DNA from a similar sized stable region of the
      mitochondrial genome. The end-point of this assay is the dilution that can just
      detect any PCR product; however, this is an inherently unstable measure. We
      constructed a chimaeric DNA construct that binds to both control and deletion
      primers with similar annealing properties. This was used in a competitive PCR
      assay to quantify Delta4977 in human testicular tissues that had been well
      characterized using the serial dilution approach. We found the competitive assay
      to be highly replicable as it compares the PCR product of the construct with that
      of test DNA samples during the linear growth phase of the PCR reaction. Moreover,
      the serial dilution assay was shown to significantly overestimate the amounts of
      deleted mitochondrial DNA present. The assay promises to throw new light on the
      role of mitochondrial DNA deletions in tissue dysfunction and ageing, as such
      deletions can now be determined with high accuracy and repeatability and is much
      cheaper to apply than real-time fluorescent quantitative PCR.

PMID- 11228252
TI  - Single intragenic microsatellite preimplantation genetic diagnosis for cystic
      fibrosis provides positive allele identification of all CFTR genotypes for
      informative couples.
AB  - This study is part of a strategy aimed at using fluorescent polymerase chain
      reaction (PCR) on informative genetic microsatellite markers as a diagnostic tool
      in preimplantation genetic diagnosis (PGD) of severe monogenic disease. Two
      couples, both of whom had previously had children who were compound heterozygote
      for severe cystic fibrosis mutations, were offered PGD using fluorescent PCR of
      the highly polymorphic cystic fibrosis transmembrane conductance regulator (CFTR)
      intragenic microsatellite marker IVS17bTA. Cleavage-stage embryo biopsy followed
      by PCR resulted in transfer of one unaffected carrier embryo for each couple.
      This approach eliminates the need for single cell multiplex PCR strategies to
      detect CF compound heterozygotes. It also provides a control of chromosome 7
      ploidy in the blastomeres and a selection against allele dropout by positive
      detection of each CFTR copy of all genotypes in preimplantation embryos from
      genetically informative families.

PMID- 11228253
TI  - The benefits of long-term inhaled glucocorticosteroid treatment in children with
      asthma outweigh the risks.

PMID- 11228254
TI  - IL-12 and IFN-gamma deficiencies in human neonates.

PMID- 11228255
TI  - Proton magnetic resonance spectroscopy ((1)H-MRS) in neonatal brain injury.

PMID- 11228256
TI  - The neurobiology and consequences of epilepsy in the developing brain.
AB  - Epilepsy is a disorder in which the balance between cerebral excitability and
      inhibition is tipped toward uncontrolled excitability. There is now clear
      evidence that there are distinct differences between the immature and mature
      brain in the pathophysiology and consequences of seizures. Both the enhanced
      excitability of the immature brain compared with the mature brain and the unique
      pathologic consequences of seizures are related to the sequential development and
      expression of essential signaling pathways. Although the immature brain is less
      vulnerable than the mature brain to seizure-induced cell death, seizures in the
      developing brain can result in irreversible alterations in neuronal connectivity.
      Developing novel strategies to treat and avert the consequences of seizures in
      children will require further understanding of the unique mechanisms of seizure
      initiation and propagation in the immature brain.

PMID- 11228257
TI  - Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency: clinical course
      and description of causal mutations in two patients.
AB  - Hereditary deficiency of mitochondrial HMG-CoA synthase (mHS, OMIM 600234) is a
      poorly defined, treatable, probably underdiagnosed condition that can cause
      episodes of severe hypoketotic hypoglycemia. We present clinical follow-up and
      molecular analysis of the two known mHS-deficient patients. The diagnosis of mHS
      deficiency is challenging because the symptoms and metabolite pattern are not
      specific. Moreover, enzyme analysis is technically difficult and requires
      sampling of an expressing organ such as liver. The patients, now aged 16 and 6 y,
      have normal development and have had no further decompensations since diagnosis.
      Patient 1 is homozygous for a phenylalanine-to-leucine substitution at codon 174
      (F174L). Interestingly, although the F174 residue is conserved in vertebrate mHS
      and cytoplasmic HS isozymes, a Leu residue is predicted in the corresponding
      position of HS-like sequences from Caenorhabditis elegans, Arabidopsis thaliana,
      and Brassica juncea. Bacterial expression of human F174L-mHS produces a low level
      of mHS polypeptide with no detectable activity. Similarly, in purified
      cytoplasmic HS, which in contrast to purified human mHS is stable and can be
      studied in detail, the corresponding F-->L substitution causes a 10,000-fold
      decrease in V(max) and a 5-fold reduction in thermal stability. Patient 2 is a
      genetic compound of a premature termination mutation, R424X, and an as-yet
      uncharacterized mutant allele that is distinguishable by intragenic single
      nucleotide polymorphisms that we describe. Molecular studies of mHS are useful in
      patients with a suggestive clinical presentation.

PMID- 11228258
TI  - Establishment of an in vivo model for pediatric Ewing tumors by transplantation
      into NOD/scid mice.
AB  - Ewing tumors are a clinically heterogeneous group of childhood sarcomas that
      represent a paradigm for understanding solid tumor biology, as they are the first
      group of sarcomas for which a chromosome translocation has been characterized at
      the molecular level. However, the biologic organization of the tumor, especially
      the processes that govern proliferation, differentiation, and metastasis of
      primitive tumor stem cells is poorly understood. Therefore, to develop a
      biologically relevant in vivo model, five different Ewing tumor cell lines and
      primary tumor cells from three patients were transplanted into immune-deficient
      mice via intravenous injection. NOD/scid mice that carry a complex immune
      deficiency and thus nearly completely lack the ability to reject human cells were
      used as recipients. Overall, 26 of 52 mice (50%) transplanted with VH-64, WE-68,
      CADO-ES1, TC-71, and RM-82 cells and 4 of 10 mice (40%) transplanted with primary
      tumor cells engrafted. Moreover, primary cells that did not grow in vitro
      proliferated in mice. The pattern of metastasis was similar to that in patients
      with frequent metastases in lungs (62%), bone marrow (30%), and bone (23%). Using
      limiting dilution experiments, the frequency of the engraftment unit was
      estimated at 1 Ewing tumor-initiating cell in 3 x 10(5) VH-64 cells. These data
      demonstrate that we have been able to establish an in vivo model that
      recapitulates many aspects of growth and progression of human Ewing tumors. For
      the first time, this model provides the opportunity to identify and characterize
      primitive in vivo clonogenic solid tumor stem cells. This model will, therefore,
      be instrumental in studying many aspects of tumor cell biology, including organ
      selective metastasis and tumor angiogenesis.

PMID- 11228259
TI  - A novel model of murine mucopolysaccharidosis type VII due to an intracisternal a
      particle element transposition into the beta-glucuronidase gene: clinical and
      pathologic findings.
AB  - We describe the clinical and pathologic findings in a murine model of
      mucopolysaccharidosis VII (Sly disease) that arose spontaneously in the C3H/HeOuJ
      mouse strain. Affected gus(mps2J)/gus(mps2J) mice are deficient in beta
      glucuronidase because of insertion of an intracisternal A particle element into
      intron 8 of the gus structural gene. This is the first model of a human lysosomal
      storage disease caused by an intracisternal A particle element insertion. Mice
      with the gus(mps2J)/gus(mps2J) genotype have < 1% of normal beta-glucuronidase
      activity and secondary elevations of other lysosomal enzymes. The phenotype
      includes shortened life-span, dysmorphic features, and skeletal dysplasia.
      Lysosomal storage of glycosaminoglycans is widespread and affects the brain,
      skeleton, eye, ear, heart valves, aorta, and the fixed tissue macrophage system.
      Thus the phenotypic and pathologic alterations in gus(mps2J)/gus(mps2J) mice are
      similar to those in patients with mucopolysaccharidosis VII. The finding of
      antibodies to beta-glucuronidase in some older gus(mps2J)/gus(mps2J) mice
      suggests the mice produce sufficient enzyme to elicit an immune response. The
      gus(mps2J)/gus(mps2J) model provides another well-defined genetic system for the
      study of the pathophysiology of mucopolysaccharidosis and for evaluation of
      experimental therapies for lysosomal storage diseases. The disease in
      gus(mps2J)/gus(mps2J) mice is less severe than that seen in the previously
      characterized B6.C-H2(bm1)/ByBir-gus(mps)/gus(mps) mouse model. Furthermore,
      unlike gus(mps)/gus(mps) mice, gus(mps2J)/gus(mps2J) mice are fertile and breed
      to produce litters, all of which are mucopolysaccharidosis VII pups. This feature
      makes them extremely useful for testing intrauterine therapies.

PMID- 11228260
TI  - Evaluation of accumulated mucopolysaccharides in the brain of patients with
      mucopolysaccharidoses by (1)H-magnetic resonance spectroscopy before and after
      bone marrow transplantation.
AB  - In seven patients with mucopolysaccharidoses (1 Hurler, 1 Hurler-Scheie, 4
      Hunter, 1 Sly), cranial (1)H-magnetic resonance spectroscopy was performed to
      evaluate the accumulation of mucopolysaccharides and biochemical changes in the
      CNS in vivo before and after bone marrow transplantation (BMT). In two of seven
      patients, (1)H-magnetic resonance spectroscopy was performed before and after
      BMT. Nuclear magnetic resonance spectra of dermatan sulfate and chondroitin
      sulfate-C and magnetic resonance spectroscopy of chondroitin sulfate-C and urine
      from patients with mucopolysaccharidoses showed resonance higher than the
      chemical shift of myoinositol in the brain (3.7 ppm). The resonance was
      considered to contain signals from mucopolysaccharide molecules. The resonance
      was measured as presumptive mucopolysaccharides (pMPS). In white matter lesions
      detected by magnetic resonance imaging, pMPS/creatine ratios and choline/creatine
      ratios were consistently higher than control ratios. In white matter without
      lesions, choline/creatine ratios were higher than control ratios. Patients with
      higher developmental quotient or intelligence quotient tended to show higher N:
      acetylaspartate/creatine ratios and lower pMPS/creatine ratios in basal ganglia.
      After BMT, the pMPS/creatine ratio in white matter lesions of patient 3, with
      Hunter syndrome, was slightly decreased, but in none of the patients was the
      ratio ever below the control ratios, even 7 y after BMT. In white matter without
      lesions, the pMPS/creatine ratio in patient 3 was decreased to the control ratios
      after BMT, but although the choline/creatine ratios were gradually decreased,
      they remained higher than the control ratio, 2 y after BMT. These results suggest
      that evaluation of pMPS, choline, and N:-acetylaspartate by (1)H-magnetic
      resonance spectroscopy is an important technique that may provide useful
      biochemical information in vivo on the neurologic process and the efficacy of BMT
      in patients with mucopolysaccharidoses.

PMID- 11228261
TI  - Value of (1)H-MRS using different echo times in neonates with cerebral hypoxia
      ischemia.
AB  - Previous studies have shown altered brain metabolism after cerebral hypoxia
      ischemia, using magnetic resonance spectroscopy with echo times (TE) of 272 and
      136 ms, based on peak-area or peak-height ratios. The present study examined the
      additional value of proton magnetic resonance spectroscopy with a short TE (31
      ms) to predict a poor outcome in neonates with brain hypoxia-ischemia. Studies
      were performed in 21 full-term neonates with perinatal asphyxia in a 1.5 tesla
      magnetic field. Proton magnetic resonance spectroscopy was performed in a single
      volume of interest including the basal ganglia. TE of 272, 136 and 31 ms were
      used. After curve-fitting procedures, peak-areas as well as peak-height ratios of
      different brain metabolites were calculated, comparing patients with a poor
      versus a good outcome. Seven neonates out of 21 had a poor outcome. Neonates with
      a poor outcome showed a significantly lower N:-acetylaspartate/choline (NAA/Cho)
      and a significantly raised lactate/NAA (Lac/NAA) ratio using TE of 272 and 136
      ms. Using a TE of 31 ms, no differences were found in glutamate/NAA (Glx/NAA),
      Glx/Cho, myo-inositol/NAA (mI/NAA), and mI/Cho ratios between neonates with a
      good and those with a poor outcome. Highest predictive values could be achieved
      for NAA/Cho with a TE of 136 ms. We conclude that low NAA/Cho and high Lac/NAA
      ratios predict a poor outcome in neonates with cerebral hypoxia-ischemia. TE of
      272 and 136 ms have a better predictive value than a TE of 31 ms.

PMID- 11228262
TI  - Oxidative and glycogenolytic cCapacities within the developing chick heart.
AB  - Cardiac morphogenesis and function are known to depend on both aerobic and
      anaerobic energy-producing pathways. However, the relative contribution of
      mitochondrial oxidation and glycogenolysis, as well as the determining factors of
      oxygen demand in the distinct chambers of the embryonic heart, remains to be
      investigated. Spontaneously beating hearts isolated from stage 11, 20, and 24HH
      chick embryos were maintained in vitro under controlled metabolic conditions.
      O(2) uptake and glycogenolytic rate were determined in atrium, ventricle, and
      conotruncus in the absence or presence of glucose. Oxidative capacity ranged from
      0.2 to 0.5 nmol O(2)/(h.microg protein), did not depend on exogenous glucose, and
      was the highest in atria at stage 20HH. However, the highest reserves of
      oxidative capacity, assessed by mitochondrial uncoupling, were found at the
      youngest stage and in conotruncus, representing 75 to 130% of the control values.
      At stage 24HH, glycogenolysis in glucose-free medium was 0.22, 0.17, and 0.04
      nmol glucose U(h.microg protein) in atrium, ventricle, and conotruncus,
      respectively. Mechanical loading of the ventricle increased its oxidative
      capacity by 62% without altering glycogenolysis or lactate production. Blockade
      of glycolysis by iodoacetate suppressed lactate production but modified neither
      O(2) nor glycogen consumption in substrate-free medium. These findings indicate
      that atrium is the cardiac chamber that best utilizes its oxidative and
      glycogenolytic capacities and that ventricular wall stretch represents an early
      and major determinant of the O(2) uptake. Moreover, the fact that O(2) and
      glycogen consumptions were not affected by inhibition of glyceraldehyde-3
      phosphate dehydrogenase provides indirect evidence for an active glycerol
      phosphate shuttle in the embryonic cardiomyocytes.

PMID- 11228263
TI  - Leucine kinetics during simultaneously administered insulin and dexamethasone in
      preterm infants with severe lung disease.
AB  - The objective of this study was to determine whether insulin administration would
      prevent the well-documented catabolic effect of dexamethasone given to preterm
      infants with chronic lung disease. We studied leucine metabolism in 11 very-low
      birth-weight infants before dexamethasone treatment and on d 2, 4, and 7
      thereafter. During the first 4 d of dexamethasone, insulin was administered i.v.
      at a dose of 0.5 (n = 7) or 1.0 (n = 5) IU/kg/d. Leucine turnover was not
      significantly different between d 0 (337 +/- 41.3 micromol leucine/kg/h), d 2
      (288 +/- 27.2 micromol leucine/kg/h), d 4 (302 +/- 22.1 micromol leucine/kg/h),
      and d 7 (321 +/- 21.2 micromol leucine/kg/h), and neither was leucine breakdown
      (272 +/- 21.9 micromol leucine/kg/h on d 0, 225 +/- 21.5 micromol leucine/kg/h on
      d 2, 231 +/- 21 micromol leucine/kg/h on d 4, and 242 +/- 17.6 micromol
      leucine/kg/h on d 7). Weight gain rates were significantly lower during the first
      week of dexamethasone treatment compared with the week before treatment or the
      second and third week. We conclude that during insulin and corticosteroid
      administration in very-low-birth-weight infants, no changes were observed in
      leucine kinetics in contrast to previous studies. The decrease in weight gain was
      not reversed.

PMID- 11228264
TI  - IGF-II and IGF binding protein (IGFBP-1, IGFBP-3) gene expression in fetal rhesus
      monkey tissues during the second and third trimesters.
AB  - The IGF system is a key modulator of somatic fetal growth. Studies with human
      fetal tissues have shown a specific spatial and temporal pattern of expression of
      IGF and IGF binding protein (IGFBP) mRNAs, but have been limited to defined
      periods during gestation (i.e. 8-20 wk gestation) because of tissue availability.
      To fully assess the role of these peptides in the primate growth process, a
      longitudinal study was conducted that focused on the expression of IGF-II and
      IGFBP-1 and IGFBP-3 genes in the rhesus monkey (Macaca mulatta). Liver, kidney,
      brain, and lung were collected from rhesus monkey fetuses approximately every 2
      wk from 65 (early second trimester) through 150 d gestation (term 165 +/- 10 d)
      (n = 50), then processed for in situ hybridization using radiolabeled human
      cDNAs. IGF-II mRNA was abundantly expressed in fetal kidney (maturing glomerulus,
      supporting mesenchyme, cells of the developing nephrons), liver (hepatocytes),
      cerebral cortex (choroid plexus, capillaries), and lung (blood vessels,
      connective tissues, lamina propria, cartilage framework). IGFBP-1 was expressed
      only in the hepatocytes and IGFBP-3 mRNA was modestly expressed within the kidney
      (developing nephrons, collecting system mesenchyme), and liver (hepatocytes).
      These studies have shown that (1) IGF-II, IGFBP-1, and IGFBP-3 are expressed in
      specific cell types of the fetal monkey indicating a paracrine/autocrine role
      during development; (2) changes in IGF-II and IGFBP mRNA expression occur with
      advancing gestation; and (3) fetal monkey tissues express IGF-II and IGFBPs in a
      similar manner when compared with the human fetus.

PMID- 11228265
TI  - Hypocarbia during the first 24 postnatal hours and white matter echolucencies in
      newborns < or = 28 weeks gestation.
AB  - The purpose of the present study was to test the hypothesis that newborns < or =
      28 wk gestation who have a PCO(2) measurement in the lowest gestational age
      specific quartile (hypocarbia) on the first day of life are not at increased risk
      for ultrasonographic white matter echolucency (EL) after adjustment for
      confounders. The sample consisted of 799 infants < or = 28 wk gestation born
      during 1991-1993. Forty-eight infants with EL were classified as cases and
      compared with 751 controls, i.e. those without EL. We performed univariable
      comparisons, stratified analyses, and multivariable logistic regression. In the
      univariable analyses, hypocarbia on the first day of life was associated with an
      increased EL risk. The odds ratios for the hypocarbia-EL relationship were
      prominently elevated in the strata of infants who did not have other major risk
      factors for EL (e.g. gestational age 26-28 wk, normothyroxinemia, no
      characteristics of antenatal infection). In the multivariable analyses, the
      association diminished after adjustment with a hypocarbia propensity score (odds
      ratio = 1.7; 95 % confidence interval, 0.8-3.2) or with potential confounders.

PMID- 11228266
TI  - In vitro validation and clinical testing of an indirect calorimetry system for
      ventilated preterm infants that is unaffected by endotracheal tube leaks and can
      be used during nasal continuous positive airway pressure.
AB  - Energy expenditure measurements in ventilated preterm infants are difficult
      because indirect calorimetry underestimates energy expenditure during gas leaks
      around uncuffed endotracheal tubes routinely used in preterm infants or during
      nasal continuous positive airway pressure (CPAP). We, therefore, developed a
      breath collector that simultaneously sampled expired air expelled at the
      ventilator outlet and escaping via the tube leak from the infant's mouth and
      nose. Our breath collector was combined with a proprietary calorimeter (Deltatrac
      II). In vitro validation was done by methanol burning (VO(2), 13.8 mL/min;
      VCO(2), 9.2 mL/min) during intermittent positive pressure ventilation (IPPV) with
      two commonly used ventilators (Sechrist IV-100B and Infant Star). Measurement
      error was determined at different ventilator flows, peak inspiratory pressures of
      12-24 cm H(2)O, and during a complete tube leak. The mean measurement error with
      both ventilators was low (VO(2) +/- 3 %, VCO(2) +/- 2 %) even during a complete
      tube leak and did not increase with peak inspiratory pressure. The system
      response time was 2 min. In vivo measurements at the bedside were performed in 25
      preterm infants (body weight, 537-1402 g). Energy expenditure during IPPV was 40
      +/- 9 kcal/kg per day and 46 +/- 15 kcal/kg per day during nasal CPAP. The tube
      leak in the preterm infants studied during IPPV was 0 to 47 %, and during nasal
      CPAP 84 to 97 %. In conclusion, indirect calorimetry performed with our breath
      collector was accurate during IPPV and nasal CPAP and was unaffected by tube
      leaks.

PMID- 11228267
TI  - Reduced arousals following obstructive apneas in infants sleeping prone.
AB  - A decreased arousability and an increased risk for sudden infant death syndrome
      (SIDS) have been shown in infants sleeping prone. Obstructive apnea, a known risk
      factor for SIDS, is less often terminated by an arousal reaction in infants than
      in adults. The effect of body position on the arousal reaction to spontaneous
      respiratory events had not been previously studied in infants. The aim of our
      study was to see if body position has an influence on the frequency and delay of
      the arousal reaction to obstructive apnea. All obstructive events recorded during
      two successive nights in 20 infants sleeping one night prone and one night supine
      were studied. During the supine recording 153 obstructive events were detected,
      and 217 were detected during the prone session. Prone sleep was not associated
      with an increased frequency of obstructive apneas. Total sleep time was 382 min
      (range, 283-456) supine and 423 min (range, 325-521) prone (p = 0.003).
      Obstructive events duration was 6.5 s (range, 3-21.5) when sleeping supine and 8
      s (range, 3.5-30.5) when prone (p = 0.002). Behavioral arousal were found in 57.5
      % of obstructive events recorded supine and in 31.3 % of those seen prone (p <
      0.001). Arousal occurred after 8 s (range, 0-21) from the start of the
      obstructions when supine and 10.5 s (range, 3.5-23.5) when prone (p = 0.001).
      Sighs were found in 34 % of supine obstructive events and in 44.7 % of those
      prone (p = 0.040). A reaction, i.e. arousal or sigh, was found in 91.5 % of
      supine events and 76 % of those prone (p < 0.001). We conclude that when sleeping
      supine, infants arouse to obstructive events more often and after shorter delay
      than when prone.

PMID- 11228268
TI  - Xeroderma pigmentosum group G with severe neurological involvement and features
      of Cockayne syndrome in infancy.
AB  - We describe a premature, small for gestational age infant girl with
      micropthalmia, bilateral congenital cataracts, hearing impairment, progressive
      somatic and neurodevelopmental arrest, and infantile spasms. She presented a
      massive photosensitive reaction with erythema and blistering after minimal sun
      exposure, which slowly gave place to small skin cancers. Her skin fibroblasts
      were 10-fold more sensitive than normal to UV exposure due to a severe deficiency
      in nucleotide excision repair. By complementation analysis, the patient XPCS4RO
      was assigned to the very rare xeroderma pigmentosum (XP) group G (XP-G). One
      allele of her XPG gene contained a 526C-->T transition that changed Gln-176 to a
      premature UAG stop codon. Only a minor fraction of XPG mRNA was encoded by this
      allele. The second, more significantly expressed XPG allele contained a 215C-->A
      transversion. This changed the highly conserved Pro-72 to a histidine, a
      substitution that would be expected to seriously impair the 3' endonuclease
      function of XPG in nucleotide excision repair. In cases suspected of having XP
      and/or early-onset Cockayne syndrome, extensive DNA repair studies should be
      performed to reach a correct diagnosis, thereby allowing reliable genetic
      counseling and prenatal diagnosis.

PMID- 11228270
TI  - Oral carrageenan induces antigen-dependent oral tolerance: prevention of
      anaphylaxis and induction of lymphocyte anergy in a murine model of food allergy.
AB  - Immunosuppressive effects of carrageenan, a high-molecular-weight polysaccharide,
      on antibody and T cell responses have been previously demonstrated. However, its
      effect on anaphylaxis is unknown. Our objectives were to test carrageenan
      mediated oral tolerance induction in young mice subsequently sensitized to a
      common cow's milk antigen. C3H/HeJ mice were fed or not lambda-carrageenan (0.5
      g/L) and/or 0.01 mg/mL beta-lactoglobulin (BLG) for 5 d before oral sensitization
      with BLG and cholera toxin. Subsequently, the mice were challenged with BLG and
      symptom scores of anaphylaxis were recorded. Mesenteric lymph node cells, spleen
      cells, Peyer's patches cells, intraepithelial lymphocytes, and lamina propria
      lymphocytes were isolated and stimulated in vitro with BLG, IL-2, or left
      unstimulated. BLG-specific IgG, IgG(1), and IgG(2a) antibodies were measured.
      Pretreatment with carrageenan and BLG, but not pretreatment with either
      carrageenan or BLG alone or omission of pretreatment, diminished significantly
      the number of anaphylactic mice after BLG challenge (6.3 % versus 53 % in mice
      without pretreatment, p = 0.006). Mesenteric lymph nodes and spleen cells from
      pretreated mice proliferated less in presence of BLG or IL-2 than cells from
      sensitized control mice. Antigen-specific antibody production and passive
      cutaneous anaphylaxis was not suppressed by carrageenan and BLG pretreatment. In
      conclusion, carrageenan administered to young mice in conjunction with low doses
      of allergen before sensitization efficiently prevents anaphylaxis.

PMID- 11228269
TI  - Detection of apoptosis in kidney biopsies of patients with D+ hemolytic uremic
      syndrome.
AB  - In this study we have investigated the presence of apoptotic cells in renal
      biopsy material of seven patients with hemolytic uremic syndrome (HUS) by using
      an improved and stringent terminal deoxynucleotidyl nick-end labeling (TUNEL)
      technique. Renal biopsy material was taken in the second or third week after
      onset of the disease. Renal biopsy material of patients with minimal lesions
      nephrotic syndrome or thin basement syndrome were used as control. It has been
      reported that nonapoptotic cells can be labeled nonspecifically due to proteinase
      K pretreatment or a delay in fixation when only TUNEL technique is used. In post
      mortem material this delay in fixation is seen. Moreover, it has been described
      that mainly nonapoptotic cells that shows signs of active gene transcription can
      be labeled in this nonspecific way. For this reason we used the TUNEL technique
      in combination with a label for RNA synthesis and splicing factor (SC-35).
      Indeed, we found nonspecific labeling of nonapoptotic nuclei in biopsy material
      of HUS patients, but not in control biopsy material. By using co-labeling with
      RNA synthesis factor SC-35, we were able to identify true apoptotic cells. There
      was a significant increase (p < 0.05) in the presence of apoptotic cells in
      biopsy material of HUS patients compared with material of controls. About 80 % of
      apoptotic cells were detected in tubuli and only 20 % in glomeruli of the renal
      biopsies of HUS patients. Furthermore, most apoptotic cells were detected in
      those patients that had received peritoneal dialysis suggesting that there is a
      relationship between severity of the disease and amount of apoptotic cells. The
      finding of apoptotic cells suggest that apoptosis plays a role in HUS.

PMID- 11228271
TI  - Relative increase in IgG antibodies to Pseudomonas aeruginosa 60-kDa GroEL in
      prediabetic patients with cystic fibrosis.
AB  - In recent years research has focused on a possible connection between bacterial
      infection and development of diabetes mellitus. In this study, serum antibody
      responses against bacterial antigens in diabetic and nondiabetic patients with
      cystic fibrosis (CF) were evaluated. The first part of the study included 252 CF
      patients of whom 46 (18 %) had diabetes. This study showed that precipitating
      antibodies (precipitins) against Pseudomonas aeruginosa and other bacteria in
      crossed immunoelectrophoresis, and IgG antibodies against a 60-kD GroEL of P.
      aeruginosa, were highly variable and positively correlated with age. Patient
      material matched for age and sex showed no significant difference between
      diabetic and nondiabetic CF patients in precipitins or IgG antibodies to P.
      aeruginosa GroEL. Two longitudinal studies of 9 and 5 y using retrospectively
      selected sera from 29 prediabetic and 29 cross-matched nondiabetic CF patients
      were performed. As to precipitins against P. aeruginosa, we found no difference
      between the prediabetic and the nondiabetic group of patients during the study
      period. The study revealed, however, a significant increase of 24.6 % (p = 0.008)
      of IgG antibodies against P. aeruginosa 60-kD GroEL, 3-12 mo before the onset of
      diabetes in patients with CF, compared with an overall increase of 5 % to 6 % per
      year in both groups during the observation period. This study shows that diabetes
      in CF appears after a peak of serum IgG antibodies against GroEL and indicates
      that development of diabetes in CF patients may not only be caused by a
      progressive fibrosis of the pancreatic tissue, but may be augmented by a short
      term specific immunologic reaction, initially triggered by an ongoing and
      progressive pulmonary infection.

PMID- 11228272
TI  - Thyroglobulin messenger ribonucleic acid levels in the peripheral blood of
      children with benign and malignant thyroid disease.
AB  - Reverse transcriptase-PCR has identified thyroglobulin mRNA (Tg mRNA) in
      peripheral blood of normal adults and adults with thyroid cancer. However, no
      children were studied. The primary objective of this study was to determine
      whether whole blood Tg mRNA levels differ between benign and malignant thyroid
      disease in children. The secondary goals were to determine whether whole blood Tg
      mRNA levels vary with age or pubertal development among children with thyroid
      disease. Whole blood Tg mRNA levels were determined in 38 children (29 girls,
      nine boys; median age, 14.5 y; range, 4.8-20.4 y) with benign and malignant
      thyroid disease and correlated with diagnosis, age, pubertal status, thyroid
      size, and serum levels of free thyroxine, TSH, and Tg protein. Tg mRNA levels
      ranged from 3.3 to 104 pg Eq/microg total thyroid RNA (mean, 28 +/- 20.2 pg
      Eq/microg total thyroid RNA) and were similar in benign and malignant disorders
      (p = 0.67). However, in children with previously treated papillary thyroid
      cancer, Tg mRNA levels directly correlated with total body (131)I uptake (p =
      0.026) and serum Tg protein (p = 0.037). There was no difference between boys and
      girls, and no change with pubertal maturation. In children with benign thyroid
      disease, Tg mRNA levels correlated with serum TSH (p = 0.031), but not with
      diagnosis, age, Tanner stage, or thyroid size. We conclude that Tg mRNA levels
      are similar in children with benign and malignant thyroid disease and unchanged
      by age or pubertal status, but correlated with tumor burden in previously treated
      papillary thyroid cancer.

PMID- 11228273
TI  - Superoxide anion generation in human milk macrophages: opsonin-dependent versus
      opsonin-independent stimulation compared with blood monocytes.
AB  - Macrophages are believed to play an important role within the immunoprotective
      effects of human breast milk. It was the purpose of this study to evaluate the
      capability of human milk macrophages (MMPhi) to generate superoxide anions (O2(
      )) in comparison with peripheral blood monocytes (BMo) after stimulation with
      opsonized and unopsonized zymosan. Potential inhibitors of attachment and
      phagocytosis such as mannose and cytochalasin B were used. Expression of the
      mannose receptor on MMPhi was demonstrated by staining with MAb. BMo generated
      more O2(-) than MMPhi (417 +/- 79 versus 216 +/- 15 nmol O2(-)/mg protein, p <
      0.05) after stimulation with opsonized zymosan. When unopsonized zymosan was used
      as a serum-independent stimulus, BMo generated slightly less O2(-) in comparison
      with MMPhi (150 +/- 34 versus 176 +/- 18 nmol O2(-)/mg protein, p < 0.05). These
      findings imply a higher proportion of opsonin-independent phagocytosis in MMPhi
      than in BMo (82 versus 36 %). Preincubation with mannose resulted in a
      significantly higher reduction of O2(-) generation in MMPhi compared with BMo
      stimulated with opsonized zymosan, whereas no difference was found when
      unopsonized zymosan was used. After addition of cytochalasin B, equal inhibition
      of O2(-) generation was observed regardless of the cell type or stimulus used.
      Thus, MMPhi are stimulated to a greater extent by serum-independent mechanisms
      than BMo. As opsonins like complement or IgG are rare in the colostrum and the
      neonatal intestinal environment, such a differentiation toward serum-independent
      phagocytic abilities could play an important role for protective functions of
      human MMPhi. Possible involvement of the mannose receptor and the beta-glucan
      receptor in this specialization are discussed.

PMID- 11228274
TI  - Fast decline of hematopoiesis and uncoupling protein 2 content in human liver
      after birth: location of the protein in Kupffer cells.
AB  - Hepatic hematopoiesis is prominent during fetal life and ceases around birth. In
      rodent liver, the decline of the hepatic hematopoiesis starts abruptly at birth
      being accompanied by a decrease of mitochondrial uncoupling protein 2 (UCP2)
      expression in monocytes/macrophages, whereas hepatocytes may express UCP2 only
      under pathologic situations. The goals of this study were to characterize hepatic
      hematopoiesis in humans around birth, and to identify cells expressing UCP2.
      Hematopoiesis was evaluated histologically in the liver of 22 newborns (mostly
      very premature neonates), who died between 45 min and 140 d after birth, and one
      fetus. UCP2 expression was characterized by Northern blots, immunoblotting,
      immunohistochemistry, and by in situ hybridization. The number of hematopoietic
      cells started to decrease rapidly at birth, irrespectively of the gestational age
      (23-40 wk) of neonates. A similar decline was observed for UCP2 expression, which
      was relatively high in fetal liver. UCP2 was detected only in myeloid cells
      (mainly in Kupffer cells), but not in hepatocytes, although sepsis or other
      pathologies occurred in the critically ill newborns. Kupffer cells represent the
      major site of mitochondrial UCP2 expression in the human newborn. UCP2 may be
      essential for the differentiation and function of macrophages and serve as a
      marker for these cells in human liver during the perinatal period.

PMID- 11228275
TI  - A synthetic pentasaccharide for the prevention of deep-vein thrombosis after
      total hip replacement.
AB  - BACKGROUND: Venous thromboembolism is a frequent complication of total hip
      replacement. The pentasaccharide Org31540/SR90107A, a highly selective, indirect
      inhibitor of activated factor X, is the first of a new class of synthetic
      antithrombotic agents. To determine the optimal dose for phase 3 studies, we
      conducted a dose-ranging study in which Org31540/SR90107A was compared with a low
      molecular-weight heparin, enoxaparin, in patients undergoing total hip
      replacement. METHODS: In a double-blind study, patients were randomly assigned to
      postoperative administration of one of five daily doses of Org31540/SR90107A,
      given once daily, or to 30 mg of enoxaparin, given every 12 hours. Treatment was
      continued for 10 days or until bilateral venography was performed after a minimum
      of 5 days. RESULTS: Of 933 patients treated, 593 were eligible for the efficacy
      analysis. With Org31540/SR90107A a dose effect was observed (P=0.002), with rates
      of venous thromboembolism of 11.8 percent, 6.7 percent, 1.7 percent, 4.4 percent,
      and 0 percent for the groups assigned to 0.75 mg, 1.5 mg, 3.0 mg, 6.0 mg, and 8.0
      mg of the drug, respectively, as compared with a rate of 9.4 percent in the
      enoxaparin group. The reduction in the risk of venous thromboembolism was 82
      percent for the 3.0-mg Org31540/SR90107A group (P=0.01) and 29 percent for the
      1.5-mg group (P=0.51). Enrollment in the 6.0-mg and 8.0-mg Org31540/SR90107A
      groups was discontinued because of bleeding complications. Major bleeding
      occurred 3.5 percent less frequently in the 0.75-mg group (P=0.01) and 3.0
      percent less frequently in the 1.5-mg group (P=0.05) than in the enoxaparin group
      (in which the rate was similar to that in the 3.0-mg group). CONCLUSIONS: A
      synthetic pentasaccharide, Org31540/SR90107A, has the potential to improve
      significantly the risk-benefit ratio for the prevention of venous
      thromboembolism, as compared with low-molecular-weight heparin.

PMID- 11228276
TI  - Effects of a low-molecular-weight heparin on thrombus regression and recurrent
      thromboembolism in patients with deep-vein thrombosis.
AB  - BACKGROUND: Low-molecular-weight heparins are frequently used to treat venous
      thromboembolism, but optimal dosing regimens and clinical outcomes need further
      definition. METHODS: In this multicenter, open-label study with blinded
      adjudication of end points, we randomly assigned patients with acute deep-vein
      thrombosis to one of three treatment regimens: intravenous administration of
      unfractionated heparin; subcutaneous administration of a low-molecular-weight
      heparin, reviparin, twice a day for one week; or subcutaneous administration of
      reviparin once a day for four weeks. The primary end point was evidence of
      regression of the thrombus on venography on day 21; secondary end points were
      recurrent venous thromboembolism, major bleeding within 90 days after enrollment,
      and death. RESULTS: Of the patients receiving unfractionated heparin, 40.2
      percent (129 of 321) had thrombus regression, as compared with 53.4 percent (175
      of 328) of patients receiving reviparin twice daily and 53.5 percent (167 of 312)
      of the patients receiving reviparin once daily. With regard to thrombus
      regression, reviparin administered twice daily was significantly more effective
      than unfractionated heparin (relative likelihood of thrombus regression, 1.28;
      97.5 percent confidence interval, 1.08 to 1.52), as was reviparin administered
      once daily (relative likelihood, 1.29; 97.5 percent confidence interval, 1.08 to
      1.53). Mortality and the frequency of episodes of major bleeding were similar in
      the three groups. CONCLUSIONS: In acute deep-vein thrombosis, reviparin regimens
      are more effective than unfractionated heparin in reducing the size of the
      thrombus. Reviparin is also more effective than unfractionated heparin for the
      prevention of recurrent thromboembolism and equally safe.

PMID- 11228277
TI  - Green tea and the risk of gastric cancer in Japan.
AB  - BACKGROUND: Although laboratory experiments and case-control studies have
      suggested that the consumption of green tea provides protection against gastric
      cancer, few prospective studies have been performed. METHODS: In January 1984, a
      total of 26,311 residents in three municipalities of Miyagi Prefecture, in
      northern Japan (11,902 men and 14,409 women 40 years of age or older), completed
      a self-administered questionnaire that included questions about the frequency of
      consumption of green tea. During 199,748 person-years of follow-up, through
      December 1992, we identified 419 cases of gastric cancer (in 296 men and 123
      women). We used Cox regression to estimate the relative risk of gastric cancer
      according to the consumption of green tea. RESULTS: Green-tea consumption was not
      associated with the risk of gastric cancer. After adjustment for sex, age,
      presence or absence of a history of peptic ulcer smoking status, alcohol
      consumption, other dietary elements, and type of health insurance, the relative
      risks associated with drinking one or two, three or four, and five or more cups
      of green tea per day, as compared with less than one cup per day, were 1.1 (95
      percent confidence interval, 0.8 to 1.6), 1.0 (95 percent confidence interval,
      0.7 to 1.4), and 1.2 (95 percent confidence interval, 0.9 to 1.6), respectively
      (P for trend=0.13). The results were similar after the 117 cases of gastric
      cancer that were diagnosed in the first three years of follow-up had been
      excluded, with respective relative risks of 1.2 (95 percent confidence interval,
      0.8 to 1.8) 1.0 (95 percent confidence interval, 0.7 to 1.5), and 1.4 (95 percent
      confidence interval, 1.0 to 1.9) (P for trend=0.07). CONCLUSIONS: In a population
      based, prospective cohort study in Japan, we found no association between green
      tea consumption and the risk of gastric cancer.

PMID- 11228278
TI  - Blood-borne and sexual transmission of human herpesvirus 8 in women with or at
      risk for human immunodeficiency virus infection.
AB  - BACKGROUND: Human herpesvirus 8 (HHV-8), the causal agent of Kaposi's sarcoma, is
      transmitted sexually among homosexual men, but little is known of its
      transmission among women. Although HHV-8 has been detected in blood, there has
      been no clear evidence of blood-borne transmission. METHODS: We identified risk
      factors for HHV-8 infection in 1295 women in Baltimore, Detroit, New York, and
      Providence, Rhode Island, who reported high-risk sexual behavior or drug use. HHV
      8 serologic studies were performed with two enzyme-linked immunosorbent assays.
      RESULTS: In univariate analyses, HHV-8 was associated with black race, Hispanic
      ethnic background, a lower level of education, and infection with syphilis, the
      human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus
      (HCV). The risk of seropositivity for HHV-8 increased with the frequency of
      injection-drug use (P<0.001); HHV-8 seroprevalence among the women who used drugs
      daily was three times that among women who never injected drugs. Among the women
      with a low risk of sexual transmission, HHV-8 seroprevalence was 0 percent in
      those who had never injected drugs and 36 percent in those who had injected drugs
      (P<0.001). However, injection-drug use was linked less strongly to HHV-8
      infection than to infection with HBV or HCV. In a multivariate analysis,
      independent predictors of HHV-8 seropositivity included HIV infection (odds
      ratio, 1.6; 95 percent confidence interval, 1.1 to 2.2), syphilis infection (odds
      ratio, 1.8; 95 percent confidence interval, 1.1 to 2.8), and daily injection-drug
      use (odds ratio, 3.2; 95 percent confidence interval, 1.4 to 7.6). CONCLUSIONS:
      Both injection-drug use and correlates of sexual activity were risk factors for
      HHV-8 infection in the women studied. The independent association of HHV-8
      infection with injection-drug use suggests that HHV-8 is transmitted through
      needle sharing, albeit less efficiently than HBV, HCV, or HIV.

PMID- 11228279
TI  - Images in clinical medicine. Chronic thromboembolic pulmonary hypertension.

PMID- 11228280
TI  - Underuse of coronary revascularization procedures in patients considered
      appropriate candidates for revascularization.
AB  - BACKGROUND: Ratings by an expert panel of the appropriateness of treatments may
      offer better guidance for clinical practice than the variable decisions of
      individual clinicians, yet there have been no prospective studies of clinical
      outcomes. We compared the clinical outcomes of patients treated medically after
      angiography with those of patients who underwent revascularization, within groups
      defined by ratings of the degree of appropriateness of revascularization in
      varying clinical circumstances. METHODS: This was a prospective study of
      consecutive patients undergoing coronary angiography at three London hospitals.
      Before patients were recruited, a nine-member expert panel rated the
      appropriateness of percutaneous transluminal coronary angioplasty (PTCA) and
      coronary-artery bypass grafting (CABG) on a nine-point scale (with 1 denoting
      highly inappropriate and 9 denoting highly appropriate) for specific clinical
      indications. These ratings were then applied to a population of patients with
      coronary artery disease. However, the patients were treated without regard to the
      ratings. A total of 2552 patients were followed for a median of 30 months after
      angiography. RESULTS: Of 908 patients with indications for which PTCA was rated
      appropriate (score, 7 to 9), 34 percent were treated medically; these patients
      were more likely to have angina at follow-up than those who underwent PTCA (odds
      ratio, 1.97; 95 percent confidence interval, 1.29 to 3.00). Of 1353 patients with
      indications for which CABG was considered appropriate, 26 percent were treated
      medically; they were more likely than those who underwent CABG to die or have a
      nonfatal myocardial infarction--the composite primary outcome (hazard ratio,
      4.08; 95 percent confidence interval, 2.82 to 5.93)--and to have angina (odds
      ratio, 3.03; 95 percent confidence interval, 2.08 to 4.42). Furthermore, there
      was a graded relation between rating and outcome over the entire scale of
      appropriateness (P for linear trend=0.002). CONCLUSIONS: On the basis of the
      ratings of the expert panel, we identified substantial underuse of coronary
      revascularization among patients who were considered appropriate candidates for
      these procedures. Underuse was associated with adverse clinical outcomes.

PMID- 11228281
TI  - Tolerance and autoimmunity.

PMID- 11228282
TI  - Aspiration pneumonitis and aspiration pneumonia.

PMID- 11228283
TI  - Health policy 2001--a new series.

PMID- 11228284
TI  - Redesigning heparin.

PMID- 11228286
TI  - Are appropriateness criteria ready for use in clinical practice?

PMID- 11228285
TI  - Green tea and gastric cancer.

PMID- 11228287
TI  - The implications of the 2000 election.

PMID- 11228289
TI  - Correction: Hyperparathyroid and Hypoparathyroid Disorders. 

PMID- 11228288
TI  - Correction: Androgen-Insensitivity Syndrome as a Possible Coactivator Disease. 

PMID- 11228290
TI  - Probability of Nd:YAG laser capsulotomy after cataract surgery in Olmsted County,
      Minnesota.
AB  - PURPOSE: To estimate the cumulative probability of Nd:YAG laser posterior
      capsulotomy after cataract extraction in a geographically defined population.
      METHODS: Rochester Epidemiology Project databases were used to identify
      retrospectively all Nd:YAG laser posterior capsulotomies performed on Olmsted
      County, Minnesota, residents who had previously undergone cataract extraction
      between 1988 and 1996, inclusive. Demographic data and potential risk factors for
      laser, including age, sex, surgical technique, year of surgery, and intraocular
      lens material, were obtained by chart review or by retrieval from computer
      databases. The cumulative probability of Nd:YAG laser posterior capsulotomy was
      calculated by Kaplan-Meier estimates, and risk factors were analyzed using the
      Cox proportional hazards model. RESULTS: A total of 925 Nd:YAG laser posterior
      capsulotomies were identified after 3541 cataract extractions in 2718 patients.
      The cumulative probability of Nd:YAG laser posterior capsulotomy after cataract
      surgery was 6% (95% confidence interval = 5% to 7%) at 1 year, increasing to 38%
      (35% to 40%) at 9 years. Young age at the time of surgery (P =.02),
      polymethylmethacrylate intraocular lens material (P <.001), earlier year of
      surgery (P <.001), and extracapsular extraction (in comparison with
      phacoemulsification, P <.001) were found to increase significantly the risk of
      subsequent Nd:YAG laser posterior capsulotomy. Women tended to have a greater
      probability of Nd:YAG laser posterior capsulotomy (P =.17), but this difference
      was not statistically significant. CONCLUSIONS: Nd:YAG laser posterior
      capsulotomy was common after cataract surgery but infrequent during the first
      postoperative year. Prolonged follow-up is necessary in investigations of the
      effects of new cataract surgery technologies on the probability of capsulotomy.

PMID- 11228291
TI  - The age-related eye disease study (AREDS) system for classifying cataracts from
      photographs: AREDS report no. 4.
AB  - PURPOSE: To describe the system for grading cataracts from photographs in the Age
      Related Eye Disease Study (AREDS). METHODS: The system for grading cataracts in
      AREDS uses photographs taken in a standardized fashion with specially modified
      cameras at 11 clinical centers. The photographs are evaluated by graders for
      quality and cataract severity at a central reading center. The area of lens
      involvement is used to assess the severity of cortical and posterior subcapsular
      opacities. Optical density of nuclear opacity is graded against a series of seven
      standard photographs. Contemporaneous variability in grading is evaluated
      periodically by having a second examiner regrade a subset of the photographs.
      Temporal variability is assessed by annually regrading a subset of photographs.
      RESULTS: Photographs of 925 eyes, most with no or early lens opacities, were
      regraded to assess intergrader reliability. For cortical opacities, there was an
      absolute difference of 10% or greater of area involved in 1.9% of the replicate
      gradings. For posterior subcapsular opacities an absolute difference of 5% of
      area involved was noted in 2.8% of the regraded photographs. For nuclear
      opacities, absolute differences of 1.5 or more steps were observed in 0.6% of
      eyes. There was little evidence of temporal drift in grading any of the three
      types of opacity during four annual regrades. CONCLUSIONS: We have demonstrated a
      high degree of reliability in grading the severity of lens opacities in a large
      study cohort with mostly early lens changes, the type of cohort most likely to be
      entered in clinical trials involving cataract prevention. The Age-Related Eye
      Disease Study System for Classifying Cataracts From Photographs could be useful
      in studies where there is a need to standardize data collection over time and
      across different data collection sites. Limitations of the system include the
      cost of implementation and, currently, the limited amount of data on grading
      reproducibility for more advanced lens opacities.

PMID- 11228293
TI  - Disinfection of Goldmann tonometers after contamination with hepatitis C virus.
AB  - PURPOSE: To compare methods of disinfecting Goldmann tonometer tips inoculated
      with hepatitis C virus. METHODS: Hepatitis C virus was placed on Goldmann
      tonometer tips, air dried, and then disinfected by dry gauze wipes, isopropyl
      alcohol wipes, cold water washes, povidone iodine 10% wipes, and hydrogen
      peroxide or isopropyl alcohol soaks followed by a cold water wash and dry.
      Hydrogen peroxide and isopropyl alcohol disinfection techniques followed the
      Centers for Disease Control and Prevention guidelines for prevention of possible
      transmission of human immunodeficiency virus (HIV). After disinfection, samples
      from tonometer tips were amplified by polymerase chain reaction to quantitate the
      amount of hepatitis C virus RNA remaining. RESULTS: Percentage of hepatitis C
      virus RNA remaining after disinfection: dry gauze wipes 95.65%, isopropyl alcohol
      5-second wipes 88.91%, cold water wash 4.78%, povidone iodine 10% 5-second wipes
      0.72%, hydrogen peroxide soak with cold water wash 0.07%, and isopropyl alcohol
      soak and cold water wash 0.02%. CONCLUSIONS: After inoculation of Goldmann
      tonometer tips with hepatitis C virus, a 5-minute soak in 3% hydrogen peroxide or
      70% isopropyl alcohol followed by washing in cold water resulted in the greatest
      reduction in hepatitis C virus RNA.

PMID- 11228292
TI  - The prevalence and risk factors for pterygium in an adult Chinese population in
      Singapore: the Tanjong Pagar survey.
AB  - PURPOSE: To determine the prevalence and risk factors for pterygium in the
      Chinese population of Singapore. METHODS: A population-based survey was conducted
      in Singapore, an island located 1 degree north of the equator with a stable
      tropical climate. A disproportionate, stratified, clustered, random sampling
      procedure was used to select the names of 2000 Chinese people aged 40 to 79 years
      from the 1996 electoral register in the Tanjong Pagar district of Singapore.
      Selected subjects underwent a comprehensive interview and ocular examination.
      Pterygium was diagnosed and graded clinically as grade 1 (transparent), 2
      (intermediate), and 3 (opaque). Risks factors associated with pterygium and grade
      3 pterygium were evaluated with logistic regression models. RESULTS: From a total
      of 1717 eligible subjects, 1232 (71.8%) were examined. There were 120 people with
      either unilateral (n = 70) or bilateral (n = 50) pterygium, equivalent to an
      overall prevalence of 6.9% (95% confidence interval [CI], 5.2, 8.8) in the
      Chinese population aged 40 and older. The prevalence increased linearly with age
      (chi-square test of trend P <.001) and was higher among men than women (age
      adjusted odds ratio [OR], 4.2; 95% CI, 2.5, 6.9). Men aged 70 and above had the
      highest overall prevalence of 25.4% (95% CI, 18.2, 19.4), but pterygium was not
      seen in women aged 40 to -49 years. In multivariate analysis, ptergyium was
      independently associated with increasing age (OR, 7.8; 95% CI, 3.2, 18.8 for
      persons 70 to 81 years, compared with 40 to 49 years), male sex (OR, 5.1; 95% CI,
      2.9, 9.3) and certain occupations; factory workers, production workers and
      machine operators (OR, 3.1; 95% CI, 1.5, 6.3), as well as laborers and
      agricultural workers (OR, 3.3; 95% CI, 1.6, 7.0) had higher risks, compared with
      professionals and office workers. Grade 3 pterygium (n = 36) was also
      independently associated with male sex (OR, 11.6; 95% CI, 3.5, 38.6) and similar
      occupations but was not related to age. CONCLUSIONS: The prevalence of pterygium
      in Singapore is 7% among Chinese aged 40 years and older. Independent
      associations with increasing age, male sex, and occupations linked to outdoor
      work and other exposures suggest a multifactorial cause of this condition.

PMID- 11228294
TI  - Diagnostic capabilities of frequency-doubling technology, scanning laser
      polarimetry, and nerve fiber layer photographs to distinguish glaucomatous
      damage.
AB  - PURPOSE: To investigate the ability of three diagnostic tests: frequency-doubling
      technology (FDT), scanning laser polarimetry (GDx), and nerve fiber layer (NFL)
      photographs to distinguish normal from glaucomatous eyes. METHODS: Data were
      obtained in a cross-sectional, hospital clinic-based study, including one eye
      from each of 253 persons older than 40 years (68 normal, 94 glaucoma suspects and
      91 glaucoma patients). We performed a comprehensive ocular examination, as well
      as static automated perimetry (Humphrey 24-2), screening FDT, GDx, optic nerve
      stereoscopic photographs and high-contrast NFL photographs. RESULTS: The
      following were significantly different for glaucomatous patients compared with
      suspects and normals: mean values of mean deviation (MD, Humphrey 24-2) and
      corrected pattern standard deviation (CPSD), 11 GDx indices, mean FDT testing
      time and missed points, and NFL graded defects (ANOVA, Mantel-Haenszel test; p =
      0.0001). Using Humphrey 24-2 test results and clinical assessment as the defining
      features of glaucoma, we found that the optimal mix of sensitivity and
      specificity values were 84% and 100% for FDT (presence of any defect); 62% and
      96% for GDx (The Number, cut-off value of 27); and, 95% and 82% for NFL
      photographs (presence of any abnormality). FDT testing took the least time to be
      administered. CONCLUSIONS: The FDT had the best diagnostic performance. Neural
      network analysis of GDx data outperformed other elements of its software.

PMID- 11228295
TI  - Acute effect of latanoprost on pulsatile ocular blood flow in normal eyes.
AB  - PURPOSE: To determine the effect of an acute dose of 0.005% latanoprost on
      intraocular pressure and pulsatile ocular blood flow in normal eyes. METHODS:
      Nineteen volunteers received a single dose (two drops) of latanoprost 0.005% in
      one eye and placebo in the fellow control eye, randomized and masked to the
      observer. Intraocular pressure, perfusion pressure, pulsatile ocular blood flow,
      and systemic circulatory parameters were measured before and 8 hours after
      dosing. RESULTS: The mean (+/- SE) intraocular pressure, perfusion pressure, and
      pulsatile ocular blood flow before treatment were 17 +/- 1 mm Hg, 46 +/- 3 mm Hg,
      and 13 +/- 1 microl per second, respectively, in both the treated and control
      eyes. The mean intraocular pressure reduction was 4.9 and 2.1 mm Hg (28% and 12%)
      in the treated and fellow eye, respectively. The mean perfusion pressure increase
      was 5.6 and 2.8 mm Hg (12% and 6%) in the treated and fellow eye, respectively.
      The mean pulsatile ocular blood flow increase was 2.7 and 0.2 microl per second
      (20% and 1%) in the treated and fellow eye, respectively. The treated eye change
      in pulsatile ocular blood flow was not correlated to the change in perfusion
      pressure. Simultaneous reduction of intraocular pressure and increase or no
      significant change in pulsatile ocular blood flow occurred in 15 of 19 (79%) of
      the treated eyes. The systemic blood pressure and pulse rates remained in normal
      ranges over the 8-hour period. CONCLUSION: In this study, topical latanoprost
      significantly reduces intraocular pressure and increases ocular blood flow in
      normal eyes 8 hours after dosing. These effects of latanoprost may be beneficial
      in the management of glaucoma patients.

PMID- 11228296
TI  - Treatment of retinal detachment resulting from myopic macular hole with internal
      limiting membrane removal.
AB  - PURPOSE: To examine the efficacy of vitrectomy with internal limiting membrane
      removal for retinal detachment resulting from a macular hole in highly myopic
      eyes. METHODS: Eleven consecutive highly myopic eyes (11 patients) with retinal
      detachment resulting from a macular hole were treated by vitrectomy with removal
      of the internal limiting membrane, which was stained with indocyanine green and
      sulfur hexafluoride gas injection. Postoperatively, the patients were instructed
      to remain prone for 2 weeks. The excised specimens were evaluated with
      transmission electron microscopy. RESULTS: The mean postoperative follow-up was
      9.2 +/- 2.3 months (range, 7 to 13 months). In 10 of the 11 eyes (91%) the retina
      was reattached during the initial surgery. Redetachment occurred in one eye,
      which was successfully treated during the second surgery. Best-corrected visual
      acuity improved in all eyes and ranged from 20/400 to 20/50. Pathologic
      examination showed that the internal limiting membrane and epiretinal tissues
      were present in all specimens. CONCLUSIONS: The use of indocyanine green staining
      can facilitate removal of a macular internal limiting membrane and overlying
      epiretinal membrane, resulting in complete relief of the macular traction.
      Primary removal of the internal limiting membrane may contribute to a high
      initial success rate for retinal reattachment and be an important adjuvant to the
      treatment of retinal detachment resulting from a macular hole in highly myopic
      eyes.

PMID- 11228297
TI  - Pars plana vitrectomy, subretinal injection of tissue plasminogen activator, and
      fluid-gas exchange for displacement of thick submacular hemorrhage in age-related
      macular degeneration.
AB  - PURPOSE: To evaluate a new procedure for displacement of large, thick submacular
      hemorrhage in patients with age-related macular degeneration. METHODS:
      Retrospective review of 11 eyes of 11 patients with age-related macular
      degeneration and thick submacular hemorrhage (defined as causing retinal
      elevation detectable on stereo fundus photographs) treated with vitrectomy,
      subretinal injection of tissue plasminogen activator (25 or 50 microg), and fluid
      gas exchange with postoperative prone positioning. Outcome measures included
      displacement of hemorrhage from the fovea, best postoperative visual acuity, and
      final postoperative visual acuity. RESULTS: In the 11 affected eyes of 11
      patients (seven men and four women; mean age, 76 years), preoperative visual
      acuity ranged from 20/200 to hand motions. With surgery, subretinal hemorrhage
      was displaced from the fovea in all 11 cases. Mean postoperative follow-up was
      6.5 months (range, 1 to 15 months). Best postoperative visual acuity varied from
      20/30 to 5/200, with improvement in nine (82%) cases and no change in two cases.
      Eight eyes (73%) measured 20/200 or better, with four of these eyes (36%) 20/80
      or better. Final postoperative visual acuity ranged from 20/70 to light
      perception, with improvement in eight (73%) cases, no change in one case, and
      worsening in two cases. A statistically significant difference was found between
      preoperative and best postoperative visual acuity (P =.004) but not between
      preoperative and final visual acuity (P =.16). Hemorrhage recurred in three (27%)
      eyes, causing severe visual loss in one eye. CONCLUSIONS: This technique
      displaces submacular hemorrhage from the fovea and can improve vision in patients
      with age-related macular degeneration. However, recurrence of hemorrhage occurred
      in 27% of eyes and caused severe visual loss in one eye. A randomized,
      prospective clinical trial is necessary to determine the efficacy of this
      technique in comparison with other proposed treatments.

PMID- 11228298
TI  - Retinal nerve fiber layer evaluation in human immunodeficiency virus-positive
      patients.
AB  - PURPOSE: To determine the effect of human immunodeficiency virus (HIV) infection
      on topographic measures of the optic disk and the retinal nerve fiber layer.
      METHODS: A cross-sectional study at the Acquired Immunodeficiency Syndrome (AIDS)
      Ocular Research Unit at the University of California, San Diego. Retinal nerve
      fiber layer thickness at the optic nerve head was evaluated using the Heidelberg
      Retinal Tomograph, a confocal scanning laser tomograph in 38 HIV-positive and 24
      age-matched HIV-negative subjects. RESULTS: HIV-positive patients without CMV
      retinitis showed significant differences from HIV-negative normal controls in a
      number of measures of the retinal nerve fiber layer. This indicated a loss of
      retinal ganglion cells in HIV-positive patients without retinitis. HIV-positive
      patients with CMV retinitis were worse in most measurements than both HIV
      negative controls and HIV-positive patients without CMV. CONCLUSIONS: Significant
      thinning of the retinal nerve fiber layer occurs in HIV-positive patients without
      infectious retinopathy, and there are further changes in the optic disk
      associated with CMV retinitis. Confocal scanning laser tomography may be of use
      in the diagnosis of early HIV-associated visual function loss.

PMID- 11228299
TI  - Multiple arterial ectasias in patients with sarcoidosis and uveitis.
AB  - PURPOSE: To describe and evaluate the cause of a clinical entity characterized by
      bilateral intraocular inflammation, multiple arterial ectasias including beading,
      macroaneurysms, comma-like ectasias and kinking, with vasculitis, staining of the
      optic disk and multiple peripheral round punched-out hypopigmented chorioretinal
      scars in elderly patients. The formation and the course of the arterial ectasias
      is analyzed. METHODS: Seven patients with this syndrome were evaluated by
      clinical examination, fluorescein angiography, and systemic investigations.
      RESULTS: Three of the seven patients had a biopsy characteristic of sarcoidosis,
      two others showed positive bronchoalveolar lavage, as well as other analyses and
      tests suggesting sarcoidosis, and two showed other findings suggestive of
      sarcoidosis. The patients were all over 60 years of age and had arterial
      hypertension. In two patients, an arterial ectasia developed at the site of
      previous focal inflammation. The macroaneurysms either remained unchanged, became
      comma-like ectasias, arterial kinks, or completely vanished. CONCLUSION: Elderly
      patients with multiple arterial ectasias, uveitis, disk staining, and peripheral
      chorioretinitis should be thoroughly investigated for sarcoidosis. We suggest
      that sarcoidosis may cause some degree of arteritis, which may weaken the
      arterial wall, with resulting ectasia. Arterial hypertension may play a role in
      the formation of the ectasias by increasing the pressure on the arterial wall
      weakened by inflammation.

PMID- 11228300
TI  - Totally necrotic choroidal and ciliary body melanomas: associations with
      prognosis, episcleritis, and scleritis.
AB  - PURPOSE: To report associations between prognosis, total tumor necrosis,
      scleritis, and episcleritis in choroidal and ciliary body melanomas. METHODS: In
      this retrospective observational histopathologic study, 157 totally necrotic
      melanomas and 177 melanomas that were not totally necrotic of choroidal and
      ciliary body were retrieved from the Registry of Ophthalmic Pathology. The eyes
      were examined for the histologic evidence of inflammatory cells within the sclera
      and episcleral tissues. Contingency table, Kaplan-Meier, and Cox proportional
      hazard regression analyses were performed. In the survival analyses, only deaths
      with metastatic melanoma were considered as events in the statistical analysis.
      RESULTS: Among the totally necrotic melanomas, 118 of 157 (75.1%) had both
      episcleritis and scleritis; two of 157 (1.3%) had scleritis only; 29 of 157
      (18.5%) had episcleritis only; and eight of 157 (5.1%) had neither episcleritis
      nor scleritis. Among the non-necrotic melanomas, 23 of 177 (12.9%) had both
      episcleritis and scleritis; eight of 177 (4.5%) had scleritis only; 71 of 177
      (40.1%) had episcleritis only; and 75 of 177 (42.3%) had neither episcleritis nor
      scleritis. Cox regression indicated that total necrosis and scleritis were
      prognostically significant (P <.05) when analyzed univariately but not
      significant when analyzed multivariately with tumor size. CONCLUSIONS: Scleritis
      and episcleritis were statistically significantly associated with total tumor
      necrosis. There was a higher incidence of episcleritis than scleritis in both the
      necrotic and non-necrotic tumor types. Associations with patient outcome were
      identified for necrosis and scleritis. However, these associations were
      statistically insignificant when the prognostic effect of tumor size was also
      considered in a multivariate model.

PMID- 11228301
TI  - Monocular blindness as a complication of trigeminal radiofrequency rhizotomy.
AB  - PURPOSE: To raise the awareness of the rare complication of monocular blindness
      resulting from radiofrequency rhizotomy for trigeminal neuralgia. METHODS: Case
      series from tertiary referral centers. Patients were referred after complaint of
      loss of vision. RESULTS: We report three patients who had trigeminal neuralgia
      and underwent treatment by radiofrequency rhizotomy. Each developed complete loss
      of vision in one eye immediately after the procedure. One patient died of an
      unrelated cause, and pathologic analysis revealed changes compatible with acute
      trauma to the right optic nerve. CONCLUSION: Our third case confirms the
      hypothesis that traumatic optic neuropathy after trigeminal radiofrequency
      rhizotomy results from malpositioning of the rhizotomy needle through the
      inferior orbital fissure into the orbital apex rather than the foramen ovale.

PMID- 11228302
TI  - Ophthalmology resident training in refractive surgery.

PMID- 11228303
TI  - Macular translocation: unifying concepts, terminology, and classification.
AB  - PURPOSE: To describe some unifying concepts, terminology, and classification of
      macular translocation so as to facilitate communication within the scientific
      community. METHODS: A panel of ophthalmologists with expertise in macular
      translocation reviewed available data and developed some unifying concepts,
      terminology, and classification of macular translocation. RESULTS: Macular
      translocation may be defined as any surgery that has a primary goal of relocating
      the central neurosensory retina or fovea intraoperatively or postoperatively
      specifically for the management of macular disease. It may be classified
      according to the size of the retinotomy and, where applicable, the technique of
      chorioscleral shortening used. The direction of macular translocation is denoted
      by the movement of the neurosensory macula relative to the underlying tissues.
      Effective macular translocation may be defined as successful intraoperative or
      postoperative relocation of the fovea overlying a subfoveal lesion to an area
      outside the border of the lesion. The concepts of minimum desired translocation
      and median postoperative foveal displacement can give some useful idea of the
      likelihood of effective macular translocation before surgery. CONCLUSIONS: Use of
      a common standardized terminology for macular translocation will facilitate
      communication within the scientific community and enhance further research in
      this area. However, the definitions, terms, classification, and concepts
      concerning macular translocation are likely to continue to evolve as macular
      translocation undergoes further modifications and refinements.

PMID- 11228304
TI  - Laser in situ keratomileusis: association with increased width of palpebral
      fissure.
AB  - PURPOSE: To report the preoperative and postoperative palpebral fissure width in
      eyes undergoing laser in situ keratomileusis. METHODS: In a prospective study,
      165 consecutive eyes of 87 patients (41 men and 46 women with a mean +/- standard
      deviation age of 32.9 (+/-9.5) years) had laser in situ keratomileusis using a
      Summit (Waltham, MA) APEX PLUS excimer laser and a Moria (Antony, France) LSK
      microkeratome. The width of palpebral fissure was measured preoperatively, 3
      months or 6 months after laser in situ keratomileusis. Patients were classified
      into three groups as follows: hard contact lens users group (n = 61), soft
      contact lens users group (n = 63), and non-contact lens users group (n = 41).
      RESULTS: The average width of palpebral fissure increased after laser in situ
      keratomileusis in all three groups. The hard contact lens users group increased
      from 7.6 (+/-1.6) mm to 8.7 (+/-1.2) mm (P <.0001) and non-contact lens users
      group increased from 7.7 (+/-1.9) mm to 8.9 (+/-1.9) mm (P <.0001). CONCLUSION:
      These results suggest that laser in situ keratomileusis may be associated with an
      increase in the width of the palpebral fissure.

PMID- 11228305
TI  - Epithelial infectious crystalline keratopathy.
AB  - PURPOSE: To report 2 cases of epithelial infectious crystalline keratopathy.
      METHODS: Two patients (2 eyes) with significant meibomitis presented with minimal
      inflammation and plaque-like lesions on the corneal surface made of fine
      crystalline structures. Corneal scrapings of these lesions were performed for
      microbiological evaluation. The patients were treated with topical ciprofloxacin
      and artificial tears. RESULTS: Smear examination of the corneal scrapings
      revealed numerous bacteria and keratinized epithelial cells with no inflammatory
      cells. Culture showed a significant growth of Staphylococcus epidermidis and
      Corynebacterium species in the first case and Pseudomonas aeroginosa in the
      second case. The response to treatment was poor, with recurrence of the
      crystalline lesion. CONCLUSION: Infectious crystalline keratopathy lesions may
      involve the epithelium and occur on the corneal surface.

PMID- 11228306
TI  - Ocular deposition of copper associated with multiple myeloma.
AB  - PURPOSE: To report a case of hypercupremia with deposits in both eyes on the
      Descemet's membrane, surface of the iris, and lens capsule associated with
      multiple myeloma. METHOD: Case report. RESULTS: A 64-year-old white woman had
      metallic deposits in both eyes on the central Descemet's membrane, surface of the
      iris, and the anterior and posterior lens capsule. A systemic examination
      revealed an elevated serum copper, normal serum ceruloplasmin, and an increased
      level of total protein and IgG kappa gammaglobulin. Based on these results, she
      was diagnosed with multiple myeloma. CONCLUSIONS: Copper deposits on the
      Descemet's membrane, surface of the iris, and lens capsule may be the first sign
      of multiple myeloma.

PMID- 11228307
TI  - Amelanotic corneal melanoma after a blast injury.
AB  - PURPOSE: To report a case of a corneal melanoma after trauma. METHODS: Case
      report. RESULTS: A 68-year-old man sustained an ocular injury from a blast
      furnace explosion in 1958. In 1998, he underwent a penetrating keratoplasty for a
      corneal scar. Histologic examination and cell markers of the host button revealed
      intrastromal and subepithelial melanoma. No clinical or microscopic evidence of
      adjacent conjunctival or uveal melanoma was found. CONCLUSION: Melanoma of the
      cornea can present as a stromal opacity after trauma.

PMID- 11228308
TI  - Pigmentary dispersion syndrome induced by a posterior chamber phakic refractive
      lens.
AB  - PURPOSE: To report a case of bilateral pigmentary dispersion syndrome (PDS)
      induced by the implantation of posterior chamber phakic refractive lenses (PRLs).
      METHOD: Case report. RESULTS: Following bilateral implantation of posterior
      chamber phakic refractive lenses in 38-year-old woman, unilateral elevated
      intraocular pressure (IOP) developed within months that was attributable to
      pigment dispersion within the anterior chamber. Findings consistent with PDS
      included bilateral transillumination defects of the iris in areas contacting the
      anterior surface of the PRLs, pigment deposits on the anterior surface of the
      PRLs, Krukenberg spindles, and bilateral dense pigmentation of the trabecular
      meshwork. The patient's IOP is presently under control and she has not developed
      glaucomatous damage. CONCLUSIONS: The development of PDS in this case
      demonstrates that posterior chamber phakic refractive lenses can make contact
      with the posterior iris and induce pigment dispersion syndrome in susceptible
      patients.

PMID- 11228309
TI  - Needle aspiration and endodiathermy treatment of epithelial inclusion cyst of the
      iris.
AB  - PURPOSE: To report a case of recurrent epithelial inclusion cyst of the iris
      treated with needle aspiration and endodiathermy. METHODS: Case report. A 27-year
      old man with a history of congenital cataracts, congenital nystagmus, cataract
      surgery in each eye at 3 years of age, and a long-standing iris epithelial cyst
      presented with decreased vision of 20/400 in the better seeing left eye. The
      reduced vision was diagnosed secondary to growth of the iris inclusion cyst over
      the pupil. RESULTS: The iris cyst, which occluded the chamber angle and pupil,
      was treated with aspiration, separation of the cyst wall from the cornea, and
      endodiathermy. Twelve months after cyst surgery, no evidence existed of
      epithelial cyst regrowth. The visual function was significantly improved,
      although Snellen visual acuity was unchanged at 20/400. CONCLUSION: The minimal
      invasiveness of needle aspiration and diathermy can result in a satisfactory
      outcome without undertaking more extensive and invasive surgical treatments for
      epithelial inclusion cysts of the anterior chamber.

PMID- 11228310
TI  - Dislocated intraocular lens fixation using intraocular cowhitch knot.
AB  - PURPOSE: To describe a technique for suturing a dislocated intraocular lens (IOL)
      using an intraocular cowhitch knot without IOL extraction. METHODS: Through the
      sideports of paracentesis, a cowhitch knot is made outside of the anterior
      chamber by looping 10-0 Prolene around the haptics of the IOL. The knot is then
      tied in the anterior chamber by pulling up the suture. After repeating this for
      the opposite side, the cowhitch knots are fixated to the ciliary sulcus. RESULTS:
      In 4 cases treated this way, the IOL remained well positioned. CONCLUSION: This
      technique enables secure fixation of the IOL haptics.

PMID- 11228311
TI  - A new surgical technique for the management of orbital fat prolapse.
AB  - PURPOSE: To present a new surgical technique for the management of orbital fat
      prolapse. METHODS: Four eyes of three patients (average age +/- SD: 73.0 +/- 6.9
      years; range, 69 to 81 years) who presented with orbital fat prolapse were
      treated with conjunctival fixation to the sclera approximately 8 to 10 mm
      posterior to the corneoscleral limbs in the area of orbital fat prolapse with
      four to seven 6.0 Vicryl (polyglactin 910, Johnson & Johnson, New Brunswick, New
      Jersey) stitches. RESULTS: The treatment with conjunctival fixation to the sclera
      was successful in all four eyes, and during a mean follow-up period of 357.5 days
      (+/-SD: +/-189 days; range, 641 to 263 days), there has been no recurrence of
      orbital fat prolapse. CONCLUSION: We successfully treated orbital fat prolapse
      with conjunctival fixation to the sclera, a new surgical approach for this
      condition.

PMID- 11228312
TI  - Spontaneous regression and disappearance of subclinical rhegmatogenous retinal
      detachment.
AB  - PURPOSE: To report spontaneous regression and disappearance of subclinical
      rhegmatogenous retinal detachment. METHODS: Case reports. RESULTS: Three separate
      areas of subclinical retinal detachment in two eyes of two patients were followed
      without treatment for 35 years (Case 1) and 28 years (Case 2). The three areas of
      subclinical retinal detachment spontaneously regressed and disappeared. There has
      been no recurrence of subclinical retinal detachment in Case 1 for 12 years and
      14 years, and in Case 2 for 12 years. CONCLUSION: Subclinical retinal detachment
      can show spontaneous regression and disappearance as its natural outcome when
      observed without intervention.

PMID- 11228313
TI  - Correction of cyclovertical strabismus induced by limited macular translocation
      in a case of age-related macular degeneration.
AB  - PURPOSE: To report a case of strabismus surgery performed to treat cyclovertical
      strabismus induced by limited macular translocation. METHODS: Case report.
      RESULTS: A 62-year-old man suffering with age-related macular degeneration and
      subfoveal choroidal neovascularization, RE, underwent limited macular
      translocation surgery. The fovea was rotated downward, and his visual acuity
      improved from 20/100 to 20/25 postoperatively. Cyclovertical diplopia persisted
      for 6 months after the operation. A Hess screen test revealed a pattern that
      simulated an underaction of the superior oblique muscle and inferior rectus
      muscle with an overaction of the ipsilateral inferior oblique muscle. To treat
      the diplopia, advancement of the superior oblique muscle tendon and resection of
      the ipsilateral inferior rectus muscle were performed. Binocular single vision
      with 140 seconds of arc for stereopsis was obtained. CONCLUSION: Cyclovertical
      strabismus after limited macular translocation is corrective with conventional
      surgery on the treated eye.

PMID- 11228314
TI  - Limited macular translocation for the management of subfoveal retinal pigment
      epithelial loss after submacular surgery.
AB  - PURPOSE: To report a case of subfoveal retinal pigment epithelial (retinal
      pigment epithelium) loss after submacular surgery managed successfully by limited
      macular translocation. METHODS: Case report. RESULTS: A 28-year-old woman
      presented with a visual acuity of 20/100 caused by subfoveal choroidal neovas
      cularization secondary to ocular histoplasmosis syndrome. Submacular resection of
      the choroidal neovascularization was complicated by inadvertent retinal pigment
      epithelium loss from beneath the foveal center. She underwent limited macular
      translocation 5 days after the initial surgery and had successful displacement of
      the fovea to an area inferior to the retinal pigment epithelium defect. Her
      visual acuity was 20/60 4 months postoperatively. CONCLUSION: This report
      demonstrates the feasibility of using limited macular translocation for the
      management of eyes with central retinal pigment epithelium defect after
      submacular surgery and extends the clinical indications for limited macular
      translocation.

PMID- 11228315
TI  - Sickle cell disease presenting with extensive peri-macular arteriolar occlusions
      in a nine-year-old boy.
AB  - PURPOSE: To report a dramatic occlusive event of the macula surrounding the
      foveal avascular zone, causing severe and permanent loss of vision in a child
      with sickle cell disease. METHODS: Case report. A nine-year-old boy with SS
      hemoglobinopathy and oculocutaneous albinism developed acute unilateral loss of
      vision. RESULTS: Ophthalmoscopy revealed a pale, milky white, thickened retinal
      lesion centered on the fovea in the right eye as well as foveal hypoplasia in the
      left eye. The presence of macular malformation associated with oculocutaneous
      albinism precluded formation of a cherry-red spot. Fluorescein angiography of the
      right eye demonstrated extensive occlusions of the arterioles surrounding the
      foveal avascular zone. The presence of occlusions surrounding the fovea from
      multiple directions suggested the possibility of central retinal artery occlusion
      with migration of microemboli downstream. CONCLUSION: The patient, the youngest
      case reported, developed an irreversible macular infarction that was not improved
      by an exchange erythrocyte transfusion. He was placed on a long-term monthly
      transfusion protocol to protect his unaffected eye.

PMID- 11228316
TI  - Extramedullary plasmacytoma confined to the choroid.
AB  - PURPOSE: To report a case of an extramedullary plasmacytoma confined to the
      choroid. METHODS: Interventional case report with cytopathologic correlation.
      RESULTS: A 76-year-old asymptomatic woman presented with 2 globular orange and
      amelanotic choroidal lesions in the right eye. Fine needle aspiration biopsy of
      one of the choroidal lesions followed by immunocytochemical studies revealed
      monoclonal plasma cells, diagnostic of plasmacytoma. Systemic evaluation was
      negative, except for increased serum gamma globulin with immunoglobulin kappa
      spike on electrophoresis. The patient was managed by ocular external beam
      radiotherapy. At 9 years follow-up, she was free of local disease and never
      developed multiple myeloma. CONCLUSION: Extramedullary plasmacytoma confined to
      the choroid is rare. It may present simulating other common amelanotic choroidal
      lesions. Fine needle aspiration biopsy and proper systemic evaluation are
      critical in establishing the diagnosis.

PMID- 11228317
TI  - Aspiration cytology of metastatic chordoma to the orbit.
AB  - PURPOSE: To report a case of metastatic tumor to the left orbit from a
      sacrococcygeal chordoma. METHODS: A 48-year-old man with a sacrococcygeal
      chordoma developed left orbit swelling, left eye proptosis with deteriorating
      vision, and the inability to walk. Fine needle aspiration cytology (FNAC) of the
      orbital tumor and sacrococcygeal tumor was performed. RESULTS: Fine needle
      aspiration cytology (FNAC) showed features of sacrococcygeal chordoma with
      metastatic tumor to the left orbit. CONCLUSION: Although chordoma rarely
      metastasizes, this case demonstrates chordoma metastatic to the orbit.

PMID- 11228318
TI  - Orbital cellulitis caused by Fusobacterium necrophorum.
AB  - PURPOSE: To report the case of a previously healthy young female who developed
      orbital cellulitis caused by Fusobacterium necrophorum. We are unaware of
      previous reports of this condition caused by the same anaerobic, gram-negative,
      nonsporeforming bacterium and could find no reference to it in a computer search
      using MEDLINE. METHODS: Case report. RESULTS: In the case of orbital cellulitis
      presented here, the patient required 3 sinus debridement operations and 30 days
      of intravenous antibiotics. Despite this, her vision did not fully recover.
      CONCLUSION: F. necrophorum is capable of causing severe orbital disease that
      requires aggressive and prompt treatment to preserve sight.

PMID- 11228319
TI  - Primary cutaneous adenoid cystic carcinoma of the eyelid.
AB  - PURPOSE: To report a case of primary cutaneous adenoid cystic carcinoma involving
      the eyelid. METHODS: We examined a 70-year-old woman with an 18-month history of
      a gradually enlarging, blue-colored mass in the medial third of the right upper
      eyelid. Excisional biopsy and additional resection of the medially infiltrated
      margin resulted in tumor-free edges. Superior cervical and orbital evaluations
      were performed. RESULTS: Histopathologic evaluation revealed a primary cutaneous
      adenoid cystic carcinoma. No gland pathology was documented. No tumor recurrence
      has been noted. CONCLUSION: Primary cutaneous adenoid cystic carcinoma, an
      uncommon tumor of the skin, should be added to the differential diagnosis of
      eyelid tumors.

PMID- 11228320
TI  - Parinaud's oculoglandular syndrome attributable to an encounter with a wild
      rabbit.
AB  - PURPOSE: To describe the clinical and histopathologic findings in a patient with
      Parinaud's oculoglandular syndrome attributable to Francisella tularensis
      obtained from an encounter with a wild baby rabbit. METHODS: In an 18-year-old
      man, the clinical course, laboratory findings, and histopathologic findings are
      described. RESULTS: Parinaud's oculoglandular syndrome should be considered in
      the differential diagnosis of a patient presenting with unilateral granulomatous
      conjunctivitis, painful preauricular, and submandibular lymphadenopathy combined
      with systemic symptoms of general malaise and fever. CONCLUSION: Tularemia is one
      etiology of Parinaud's oculoglandular syndrome. It is caused by Francisella
      tularensis and is usually transmitted to humans via infected animal blood or
      through an insect bite, most often a tick. For treatment, intramuscular
      streptomycin is the drug of choice.

PMID- 11228334
TI  - The prognostic value of small-sized platelet aggregates in unstable angina:
      detection by a novel laser-light scattering method.
AB  - Platelet activation plays a pivotal role in the pathogenesis of acute coronary
      syndromes. This study was designed to evaluate the platelet aggregability in
      patients with unstable angina using a new aggregometer with laser-light
      scattering. We also examined whether there was a relationship between these
      platelet aggregabilities and unfavorable outcome during in-hospital stay. We
      measured platelet aggregability, in particular small-sized platelet aggregates in
      31 patients with unstable angina, 31 patients with stable exertional angina, and
      30 patients with chest pain syndrome. The patients with unstable angina were
      divided into two groups by their cardiac events during in-hospital stay, cardiac
      events (+)(n=11) group and cardiac events (-)(n=20) group. On admission, the
      number of small-sized platelet aggregates (V) was higher in patients with
      unstable angina (3.0+/-0.5x10(4)) than in those with stable exertional angina
      (1.4+/-0.3x10(4), P=.017) and chest pain syndrome (0.7+/-0.2x10(4), P=.0003). The
      number of small-sized platelet aggregates was higher in the cardiac events (+)
      group than in the cardiac events (-) group (5.5+/-0.9x10(4) vs. 1.6+/-0.4x10(4),
      P=.0001). A previous study elucidated that small-sized platelet aggregates
      ultimately developed into medium-sized and large-sized aggregates as platelet
      aggregation proceeds. Therefore, the production of small-sized platelet
      aggregates is more sensitive for hyperaggregability. Furthermore, the production
      of small-sized platelet aggregates increased significantly in patients with
      unstable angina than in those with stable exertional angina and chest pain
      syndrome. These findings suggest that a tendency toward thrombus formation
      increases markedly in patients with unstable angina and increased number of small
      sized platelet aggregates on admission predicts poor prognosis during in-hospital
      stay in patients with unstable angina.

PMID- 11228335
TI  - Protective effects of SM-20302, an orally active GPIIb/IIIa antagonist, in an
      ADP/epinephrine-induced guinea pig model of transient cerebral ischemia.
AB  - The potential benefits of SM-20302, (2S)-3-(3-(4
      amidinobenzoylamino)propanoylamino)-2-(4-ethyl)benzensulfonylaminopropionic acid
      hydrochloride, a nonpeptide GPIIb/IIIa receptor antagonist, were compared with
      those of aspirin and ticlopidine in a transient cerebral ischemia model in guinea
      pigs. Transient cerebral ischemia was induced in guinea pigs by an infusion of
      ADP/epinephrine into the left internal carotid artery. Each compound was orally
      administered 1 h (SM-20302 and aspirin) or 3 h (ticlopidine) before the
      ADP/epinephrine infusion. The ischemic area in coronal brain slices was assessed
      1 min after the cessation of ADP/epinephrine infusion by a carbon black perfusion
      method. In a separate experiment, neurological deficits and lactate contents of
      ipsilateral hemispheres were evaluated 60 min after the cessation of
      ADP/epinephrine infusion by neurological scores and the standard enzymatic
      method, respectively. SM-20302 (0.3 and 1 mg/kg p.o.) significantly reduced the
      ischemic area, neurological deficits and lactate contents in comparison with the
      vehicle control. Aspirin (100 mg/kg po) had no significant effect on either
      parameter. Ticlopidine (300 mg/kg p.o.) reduced the lactate content. Although a
      combination of aspirin (100 mg/kg p.o.) and ticlopidine (300 mg/kg po) also
      reduced the lactate content, no additive effect was observed. These results
      suggest that SM-20302 is of potential clinical benefit in the treatment of
      thromboembolic diseases.

PMID- 11228336
TI  - Mechanisms involved in the inhibition of neointimal hyperplasia by abciximab in a
      rat model of balloon angioplasty.
AB  - Monoclonal antibodies raised against beta(3) integrin are able to inhibit the
      binding of ligands to certain beta(3) integrins such as alpha(IIb)beta(3)
      (glycoprotein IIb/IIIa complex) and alpha(v)beta(3) (vitronectin receptor) and as
      such are inhibitors of platelet aggregation and smooth muscle cell (SMC)
      migration, both of which are involved in neointimal hyperplasia. The present
      study was designed to explore the detailed mechanisms of abciximab (Reopro), a
      monoclonal antibody (mAb) raised against alpha(IIb)beta(3) integrin in neointimal
      hyperplasia. In this study, carotid arteries of Wistar rats were damaged, and
      neointimal hyperplasia and lumen occlusion was determined at different time
      points. Abciximab was administered intravenously by an implanted osmotic pump.
      Abciximab (0.25 mg/kg/day) time-dependently inhibited both neointimal hyperplasia
      and lumen occlusion after angioplasty in carotid arteries of rats. Furthermore,
      the electromicrographs highlighted that SMCs were phenotypically different from
      the typical contractile, spindle-shaped SMCs normally seen in uninjured vessel
      walls. Platelet-derived growth factor (PDGF)-BB was strongly produced in thrombus
      formation and neointimal SMCs after angioplasty, while abciximab significantly
      reduced PDGF-BB expression in vessel lumens and neointimal SMCs after
      angioplasty. Balloon angioplasty caused a significant increase of nitrate and
      cyclic GMP as compared with sham-operated rats. Infusion of abciximab (0.25
      mg/kg/day) did not significantly change. Furthermore, the plasma level of
      thromboxane B(2) (TxB(2)) obviously increased after angioplasty, while abciximab
      markedly suppressed the elevation of plasma TxB(2) concentration. The results
      indicate that abciximab effectively prevents neointimal hyperplasia, possibly
      through the following 2 mechanisms: (1) Abciximab binds to alpha(IIb)beta(3)
      integrin on platelet membranes resulting in inhibition of platelet adhesion,
      secretion, and aggregation in injured arteries, followed by inhibition of
      thromboxane A(2) formation and PDGF-BB release from platelets. (2) Abciximab may
      also bind to alpha(v)beta(3) integrin on SMCs, thus, subsequently inhibiting cell
      migration and proliferation.

PMID- 11228337
TI  - Effects of incubation time, temperature, and anticoagulants on platelet
      aggregation in whole blood.

PMID- 11228338
TI  - Effect of activated prothrombin complex concentrate or recombinant factor VIIa on
      the bleeding time and thrombus formation during anticoagulation with a direct
      thrombin inhibitor.
AB  - Melagatran is the active form of the oral, direct thrombin inhibitor H 376/95. In
      several animal models of thrombosis, the antithrombotic properties of melagatran
      have been demonstrated, without any increase in experimental bleeding. However,
      as with all anticoagulants, in emergency situations, reversal of the
      anticoagulation may be necessary. In this study, increasing doses of activated
      prothrombin complex concentrate (APCC, Feiba) or recombinant factor VIIa (r-F
      VIIa, NovoSeven) were superimposed on high doses of melagatran, or saline, in
      anaesthetised rats. The haemostatic effect was evaluated in two bleeding time
      models and a potential prothrombotic effect was evaluated in an arterial
      thrombosis model. Compared with melagatran alone (0.5 micromol/kg/h), Feiba in
      doses of > or =25 U/kg significantly shortened the prolonged bleeding time and
      reduced blood loss. In addition, Feiba > or =50 U/kg when added to melagatran (2
      micromol/kg/h), significantly reduced bleeding time. No potentiation of thrombus
      formation was observed when Feiba was added to melagatran, compared with
      controls. NovoSeven at high doses (2-10 mg/kg) produced a nonsignificant trend in
      reduction of blood loss and with the highest dose (10 mg/kg) producing only a
      mild nonsignificant reduction in bleeding time. The prolonged prothrombin time
      (PT) and the ecarin clotting time (ECT) were more effectively shortened by Feiba
      than by NovoSeven. In contrast, whole blood clotting time (WBCT) was more
      effectively shortened by NovoSeven than by Feiba. Activated partial
      thromboplastin time (APTT) was shortened by NovoSeven but was prolonged by Feiba.
      Thrombin-antithrombin (TAT) complex formation was increased in a dose-dependent
      fashion more effectively by Feiba than by NovoSeven. CONCLUSION: Feiba (APCC)
      reversed prolonged bleeding time and blood loss in rats treated with high doses
      of melagatran and compared with the control group thrombus formation was not
      potentiated. NovoSeven (r-F VIIa) at high doses had less pronounced effects on
      blood loss and bleeding times compared with Feiba.

PMID- 11228339
TI  - Effects of agents, used to treat bleeding disorders, on bleeding time prolonged
      by a very high dose of a direct thrombin inhibitor in anesthesized rats and
      rabbits.
AB  - Melagatran is the active form of the oral, direct thrombin inhibitor, H 376/95,
      that is under evaluation in clinical trials for the prevention and treatment of
      thromboembolism. In this study, a single dose, calculated on body weight basis,
      of antifibrinolytic treatment, factor VIIa, factor VIII with and without von
      Willebrand factor (vWF), factor IX, activated (APCC) or nonactivated (PCC)
      prothrombin complex concentrates was given intravenously to rats and rabbits, in
      an attempt to reverse the prolonged bleeding time during intensive
      anticoagulation with melagatran (2 micromol/kg/h). The doses used were at or
      above human therapeutic doses. The cutaneous tail bleeding time in the rat, as
      well as the ear incision bleeding time and cuticle bleeding time, and the blood
      loss in the rabbit were used for evaluation of the hemostatic effects of these
      agents. In vivo Feiba (APCC) and Prothromplex-T (PCC) shortened the prolonged
      cutaneous bleeding times in rats (P<.05); Feiba and Autoplex (APCC) shortened the
      cutaneous bleeding times in rabbits (P<.05). In contrast, Prothromplex-T
      prolonged bleeding times and blood loss in the rabbits (P<.05). Ex vivo Feiba,
      Autoplex and NovoSeven (rF VIIa) significantly (P<.05) shortened the prolonged
      whole blood clotting time (WBCT). Prothromplex-T significantly prolonged WBCT,
      activated clotting time (ACT) and activated partial thromboplastin time (APTT).
      Feiba, Autoplex, and Prothromplex-T increased thrombin generation measured as
      increased thrombin-antithrombin complex (TAT) formation. In conclusion, APCCs
      were found to be the most effective agents for reversing bleeding time induced by
      a very high plasma concentration of melagatran. APCC and recombinant activated
      factor FVII (rF VIIa) effectively shortened the prolonged WBCT. Thus, stimulating
      thrombin generation with the use of APCC may counteract the anticoagulant effect
      observed with a very high dose of a thrombin inhibitor.

PMID- 11228340
TI  - The direct thrombin inhibitor melagatran and its oral prodrug H 376/95:
      intestinal absorption properties, biochemical and pharmacodynamic effects.
AB  - Suboptimal gastrointestinal absorption is a problem for many direct thrombin
      inhibitors. The studies presented herein describe the new oral direct thrombin
      inhibitor H 376/95, a prodrug with two protecting residues added to the direct
      thrombin inhibitor melagatran. Absorption properties in vitro: H 376/95 is
      uncharged at intestinal pH while melagatran is charged. H 376/95 is 170 times
      more lipophilic (octanol water partition coefficient) than melagatran. As a
      result, the permeability coefficient across cultured epithelial Caco-2 cells is
      80 times higher for H 376/95 than for melagtran. Pharmacokinetic studies in
      healthy volunteers: H 376/95 is converted to melagatran in man. Oral
      bioavailability, measured as melagatran in plasma, is about 20% after oral
      administration of H 376/95, which is 2.7-5.5 times higher than after oral
      administration of melagatran. The variability in the area under the drug plasma
      concentration vs. time curve (AUC) is much smaller with oral H 376/95
      (coefficient of variation 20%) than with oral melagatran (coefficient of
      variation 38%). Pharmacodynamic properties: H 376/95 is inactive towards human
      alpha-thrombin compared with melagatran [inhibition constant (K(i)) ratio, 185
      times], a potential advantage for patients with silent gastrointestinal bleeding.
      In an experimental thrombosis model in the rat, oral H 376/95 was more effective
      than the subcutaneous low molecular weight heparin dalteparin in preventing
      thrombosis. CONCLUSION: By the use of the prodrug principle, H 376/95 endows the
      direct thrombin inhibitor melagatran with pharmacokinetic properties required for
      oral administration without compromising the promising pharmacodynamic properties
      of melagatran.

PMID- 11228341
TI  - Effects of alpha(2)-macroglobulin and antithrombin on thrombin generation and
      inhibition in cord and adult plasma.
AB  - Thromboembolic complications rarely occur during infancy and childhood. It has
      been reported that increased capacity of cord plasma to inhibit thrombin due to
      elevated alpha(2)-macroglobulin (alpha(2)-M) levels may in part provide
      protection from thrombosis. In antithrombin (AT)-deficient plasma, alpha(2)-M
      exhibits anticoagulant action by complexing substantial amounts of generated free
      thrombin. It has been suggested that alpha(2)-M has the same impact on thrombin
      inhibition as AT, the most important thrombin inhibitor in adult plasma. The aim
      of our study was to examine this assumption by determining time-courses of free
      thrombin generation and prothrombin activation. Additionally, the amount of
      thrombin complexed to alpha(2)-M was assessed by comparing the heights of the end
      level of amidolytic activity curves (AACs) after extrinsic activation of platelet
      poor plasma in the presence of different concentrations of AT or alpha(2)-M.
      Increasing the AT content by 30% resulted in significantly suppressed generation
      of free thrombin and prothrombin fragment 1+2 (F1+2) in cord and adult plasma. In
      contrast, increasing the alpha(2)-M content in plasma containing physiologic
      amounts of AT by the same percentage had no effect on free thrombin generation
      and on F1+2 generation in both cord and adult plasma. In addition, the effect of
      AT supplementation on the end-level of the AACs was significantly higher compared
      to the effect of alpha(2)-M supplementation. Since alpha(2)-M, in contrast to AT,
      had no effect on free thrombin generation and prothrombin activation, our study
      suggests that the action between alpha(2)-M and thrombin might not be fast enough
      to prevent thrombin from its feedback activation in both cord and adult plasma
      and, therefore, in cord and adult plasma containing physiological amounts of AT
      alterations of the alpha(2)-M content had no effect on thrombin generation and
      inhibition.

PMID- 11228342
TI  - Effect of sepimostat mesilate on experimental venous thrombosis in rats.
AB  - Sepimostat mesilate (FUT-187: 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2
      yl) amino] benzoate dimethane sulfonate) is a newly synthesized serine protease
      inhibitor. In the present study, the oral administration of FUT-187 inhibited
      stasis-induced venous thrombosis in rats. We supposed that such effect of this
      compound was caused by its inhibitory effect on coagulation. However, the dose of
      FUT-187 that was effective at inhibiting thrombosis (10 and 30 mg/kg, po) had no
      effect on the plasma recalcification time (PRCT), activated partial
      thromboplastin time (APTT) and prothrombin time (PT) in rats. Therefore, we
      investigated the fibrinolytic activity of FUT-187 in rat plasma. The results
      revealed that rat plasma after FUT-187 administration exhibited increased
      amidolytic activity for a plasmin-, tissue-type plasminogen activator (t-PA)-,
      urokinase-type plasminogen activator (u-PA)-, factor Xa-, factor XIa- and factor
      XIIa-sensitive synthetic peptide substrate. On the other hand, the inhibitory
      effect of FUT-187 in the thrombosis model was not affected by additional
      treatment with epsilon-amino-n-caproic acid (EACA), a plasmin-mediated
      fibrinolysis inhibitor. These results suggest that even if FUT-187 enhanced
      fibrinolysis, it would be independent of a plasmin-mediated fibrinolytic pathway.
      To characterize the fibrinolytic activity, which might reduce the thrombus weight
      in the thrombosis model administered FUT-187, we carried out fibrinogen
      zymography, and clarified that FUT-187 enhanced the formation of a 20-kDa
      fibrinolytic fragment. Interestingly, this fragment was not affected by t-PA.
      Consequently, we consider that the inhibitory effect of FUT-187 on venous
      thrombosis model is caused by fibrinolysis, which is attributable to the 20-kDa
      fragment, rather than by inhibition of thrombus formation.

PMID- 11228343
TI  - Role of GATA motifs in tissue factor pathway inhibitor gene expression in
      malignant cells.
AB  - Tissue factor pathway inhibitor (TFPI) is the primary physiologic inhibitor of
      tissue factor-induced clotting. The TFPI gene contains three GATA motifs in the
      region flanking its transcription initiation sites. GATA motifs present in
      promoters of other genes bind GATA-2 transcription factor and thereby regulate
      their transcriptional expression. Both TFPI and GATA-2 transcription factor are
      synthesized by a variety of normal as well as malignant cells including
      hepatocellular carcinoma HepG2 and bladder carcinoma ECV304. Here, we studied
      whether the three GATA motifs flanking the transcription initiation sites
      regulate TFPI gene expression in HepG2 and ECV304 cells by binding to the GATA-2
      transcription factor. Synthetic oligonucleotides containing GATA sequences from
      the TFPI regulatory region formed DNA-protein complexes with HepG2 and ECV304
      nuclear extracts in an electrophoretic mobility shift assay. Using a 740-bp
      fragment (-496/+244) from TFPI regulatory region, the effect of base
      substitutions at each of the three GATA motifs was studied in a luciferase
      reporter gene system. TFPI promoter activity in HepG2 cells was increased 3-fold
      with mutation in one of the three GATA motifs and in ECV304 cells was essentially
      unchanged with mutations in all three GATA motifs. Thus, GATA motifs appear to
      serve a tissue-specific regulatory role in TFPI gene expression in malignant
      cells.

PMID- 11228344
TI  - Eye fixation related potentials in a proof reading task.
AB  - The eye fixation related potential (EFRP) associated with the occurrence of
      fixation pauses can be obtained by averaging EEGs at termination of saccades.
      EFRP is a kind of ERP measurable at the eye movement situation. Variations of
      EFRP were examined during a proof reading task for a long time. Two paragraphs of
      sentences were presented on the left and the right sides of a CRT. The paragraph
      on one side had some irrelevant words. Ten subjects were asked to detect the
      irrelevant words. The task started at 09.20 h and finished at 16.00 h and
      consisted of five blocks. The duration of each block was 1-h task and 10-min rest
      including a lunch (70 min). EEG and EOG were recorded during the task. EEGs were
      averaged at termination of saccades to obtain EFRP. EFRP showed little changes
      during the morning blocks. However, the mean amplitude between 100 and 200 ms of
      the positive component in the last two blocks decreased significantly compared
      with other blocks. The error rate, the performance and the score of fatigue
      increased at the end of the task. EFRP would reflect decline of mental
      concentration (i.e. carelessness) caused by visual fatigue.

PMID- 11228345
TI  - Brain DC potential changes of computerized tasks and paper/pencil tasks.
AB  - Analysis of slow cortical potentials and their topography is currently discussed
      as an indication of cortical activity associated with cognitive
      operations/performance. In this paper, changes of the EEG DC potential were
      analyzed in two computerized tasks (correcting typing errors, performing Excel)
      and two paper/pencil tasks (correcting typing errors, a cognitive test) to assess
      mental load related to ergonomical and task characteristics. DC recordings were
      analyzed for the mean values of baseline and the first and the second 4 min of
      each task from 24 persons. A 2 (computer usage experience low vs. high)x4
      (Task)x3 (Time: baseline, first half of task, second half)x6 (Lead) MANOVA of DC
      potential changes (DCPCs) showed at F3, F4 and C3 positive DCPCs for paper/pencil
      tasks and negative DCPCs for computerized tasks. Ratings of task difficulty were
      related to high vs. low task demands, whereas DCPCs were related to task medium,
      time on task and lead. Highly experienced persons showed a pronounced left-right
      difference at parietal locations and at frontal and central locations related to
      task medium by trend. Results were interpreted as higher cortical activation
      associated with mental load caused by additional attentional/controlling demands
      of computerized tasks.

PMID- 11228346
TI  - Estimation of an unexpected-overlooking error by means of the single eye fixation
      related potential analysis with wavelet transform filter.
AB  - An unexpected-overlooking error that caused failure to notice near the peripheral
      vision is one of the accident factors in driving behavior. We estimated how the
      unexpected-overlooking error affected the amplitude of the lambda wave in the eye
      fixation related potential (EFRP). Four subjects participated in the experiment.
      Each subject was required press the right or left switch according to the given
      task, which was that he/she pressed the right switch when the blue dot appeared
      in the right detected area or he/she pressed the left switch when the red dot
      appeared in the right. The single trial data from Pz, which referred to both
      earlobes, were analyzed by means of a wavelet transform (WT) filter. The
      difference of the lambda amplitude between the corrected data was applied for
      analysis of variance. Three subjects showed a significant effect (P<0.01 or
      P<0.05), and the remaining one subject did not show a significant consequence of
      only two errors. The unexpected-overlooking errors had a low amplitude compared
      to the mean of amplitude throughout the task. It was concluded that the amplitude
      of the lambda wave might reflect the attention level of a subject.

PMID- 11228347
TI  - Auditory probe sensitivity to mental workload changes - an event-related
      potential study.
AB  - The goal of this study was to explore the utility of parameters of ERPs for
      assessment of mental workload during performance of complex tasks. In addition to
      a baseline auditory oddball task, 15 healthy adult volunteers performed gauge
      monitoring (Gauge) and mental arithmetic (Math) separately and together.
      Throughout the task performance three types of auditory stimuli were presented as
      probes, i.e. 80% 1000 Hz tones, 10% 2000 Hz tones and 10% novel sounds. The ERP
      components N1 and P3 were analysed, which are assumed to reflect perceptive and
      central processing resources. The results interpreted in the framework of
      capacity theory indicate high demand on processing resources already during
      separate performance of both tasks Gauge or Math. During simultaneous performance
      the workload on average exceeded the limits of processing capacity: the
      performance data impaired significantly. The ERP measures N1 and P3 were
      confirmed in their sensitivity and diagnosticity. By using novel sounds as probes
      with involuntary attention-capturing properties, one might overcome a problem of
      the irrelevant probe technique, i.e. whether the operator spends his spare
      capacity for processing of the irrelevant probes.

PMID- 11228349
TI  - Social-physiological compliance as a determinant of team performance.
AB  - A cybernetic model of behavior predicts that team performance may depend on
      physiological compliance among participants. This laboratory study tested if
      compliance in electrodermal activity (EDA), heart rate or breathing in two-person
      teams (N=16) was predictive of team performance or coordination in a continuous
      tracking task simulating teleoperation. Visual contact among participants was
      manipulated. Physiological compliance was scored with weighted coherence and
      cross correlation. Separate multiple regression analyses revealed that the task
      completion time was predicted by coherence measures for EDA and heart, but only
      at a trend level for breathing. Task completion time was also predicted by heart
      cross correlation. Team tracking error was predicted by coherence measures for
      EDA, heart and breathing, and also heart cross correlation. While social-visual
      contact did not have an impact, physiological compliance was predictive of
      improved performance, with coherence robust over all three physiological
      measures. Heart cross correlation showed the strongest predictive relationships.
      These results provide evidence that physiological compliance among team members
      may benefit team performance. While further study is needed, physiological
      compliance may someday provide a needed tool for the study of team work, and an
      objective means to guide the ergonomic design of complex sociotechnical systems
      requiring a high degree of team proficiency.

PMID- 11228348
TI  - Assessment of phasic work stress using autonomic indices.
AB  - The present paper concerns the assessment of phasic work stress using autonomic
      indices such as skin temperature, respiratory measures, and heart rate, blood
      pressure, and their variabilities. A physiological model of the autonomic
      regulation of the cardiovascular and respiratory systems is also introduced in
      order to simulate and interpret the changes in these indices. Two experiments
      were conducted to investigate high tension and monotony as two types of mental
      work stress. A tracking task was used to induce high-tension work stress with and
      without an instruction intended to induce additional emotional stress. The same
      tracking task was repeated 12 times to simulate monotonous work stress. Fifty
      healthy adults participated in each experiment. Many physiological measures
      showed task-dependent changes in the high-tension experiment and at the beginning
      of the monotonous stress condition. These changes were explained by sympathetic
      activation, parasympathetic withdrawal, and respiratory rate activation. An
      additional drop in skin temperature and an additional HR increase were caused by
      the stressful instruction, which may reflect an emotional strain and can be
      explained by sympathetic activation. Furthermore, the mid-frequency component
      (approx. 0.1 Hz) of respiration and respiratory instability showed an obvious
      increase during the course of the monotonous stress experiment, which may reflect
      boredom and disgust. It was concluded that multidimensional recordings of
      autonomic measures that can be obtained during work without extra load on the
      worker would be helpful to assess different types of phasic work stress. The
      proposed model was further shown to be able to detect periods of stress in a
      complex work environment.

PMID- 11228350
TI  - Multivariate workload evaluation combining physiological and subjective measures.
AB  - This paper suggests a way to integrate different parameters into one index and
      results obtained by a newly developed index. The multivariate workload evaluation
      index, which integrates physiological parameters and one subjective parameter
      through Principle Components Analysis, was proposed to characterize task specific
      responses and individual differences in response patterns to mental tasks. Three
      different types of mental tasks were performed by 12 male participants. Heart
      rate variability, finger plethysmogram amplitude, and perspiration were used as
      physiological parameters. Three subscales, mental demand, temporal demand and
      effort out of six subscales in the NASA-Task Load Index were used as subjective
      scores. These parameters were standardized within each participant and then
      combined. It was possible to assess workload using this method from two different
      aspects, i.e. physiological and subjective, simultaneously.

PMID- 11228351
TI  - Eye blinks: new indices for the detection of deception.
AB  - Eyeblink variables were investigated while subjects performed a guilty knowledge
      test (Experiment 1) and a dual modality attention task (Experiment 2). In both
      experiments, the temporal distribution of blinks was analyzed using an automatic
      video based blink analysis system [Matsuo and Fukuda, Jpn. J. Physiol. Psychol.
      Psychophysiol., 14 (1996), 17]. In experiment 1, the blink rate pattern
      discriminated between relevant and irrelevant stimuli. In experiment 2, the blink
      rate peak after the auditory stimulus disappeared during visually attended tasks
      whereas the blink rate peak after the visual stimulus was significant during
      auditory attended tasks. It was suggested that eye blinks could be related to the
      selective attention and that eye blinks could provide an additional index for the
      detection of deception.

PMID- 11228352
TI  - Psychophysiology in ergonomics. Introduction.

PMID- 11228353
TI  - Overview of the pathogenesis, prophylaxis and therapeusis of viral hepatitis B,
      with focus on reduction to practical applications.
AB  - Hepatitis B is the most important of several hepatitis viruses of man because of
      the number of cases of the disease and the frequent occurrence of persistent
      infection that may lead to cirrhosis and cancer of the liver. The pathology of
      hepatitis B infection results mainly from the self-destructive cytotoxic T cell
      response of the host. This may be modulated by soluble pre-core e antigen of the
      virus that induces immune tolerance and by cytokines elaborated by cytotoxic T
      cells, which suppress viral replication in the infected cell. Pathogenesis of the
      disease is markedly influenced by viral mutations. Persistent hepatitis B virus
      infection may be controlled in a minority of patients by passive alpha-interferon
      therapy, and in a majority of patients by the nucleoside lamivudine until
      resistance develops. The best means to control the disease is by prevention
      through application of the highly effective vaccine prepared using surface
      antigen of the virus. It is anticipated that the gradually increasing application
      of the vaccine throughout the world may lead to elimination of hepatitis B as an
      important medical problem. This paper is intended to provide a cursory overview
      of the contemporary knowledge relating to pathogenesis, prophylaxis and
      therapeusis of human hepatitis B.

PMID- 11228354
TI  - AIDS epidemic at the beginning of the third millennium: time for a new AIDS
      vaccine strategy.
AB  - Current expansion of AIDS pandemic significantly accelerates AIDS vaccine
      research resulting in development and clinical testing of several AIDS vaccine
      candidates. At the same time, available experimental and clinical data
      demonstrate that current AIDS vaccine strategy is unsuccessful resulting in
      development of inefficient and harmful vaccines. This overview briefly summarizes
      reported results which point out the requirement for moratorium on the current
      clinical trials of HIV-1 gp120/160 vaccines and urgent need for development of a
      new, efficient and safe AIDS vaccine strategy.

PMID- 11228355
TI  - Tolerability and immunogenicity of an 11-valent pneumococcal conjugate vaccine in
      adults.
AB  - We studied the safety and immunogenicity in healthy adults of an 11-valent
      pneumococcal conjugate vaccine. Capsular polysaccharides (PS) of serotypes 1, 4,
      5, 7F, 9V, 19F and 23F were conjugated to tetanus toxoid, and of serotypes 3, 6B,
      14 and 18C to diphtheria toxoid. Ten subjects received the conjugate vaccine with
      and the other ten subjects without aluminium hydroxide adjuvant. The reference
      vaccine was a marketed 23-valent PS vaccine. Safety data were recorded over 5
      days after the immunisation. IgG antibody concentrations, avidity and subclass
      distribution were measured by EIA. The conjugate without aluminium induced more
      local adverse effects than the conjugate with aluminium or PS vaccine. All
      vaccines evoked significant antibody increases to all vaccine specific antigens.
      Both conjugate vaccines induced antibodies mainly of IgG(2) subclass, and
      adjuvanted conjugate vaccine induced IgG antibodies with increased avidity. This
      first administration, to man, of a mixed protein carrier 11-valent pneumococcal
      conjugate vaccine demonstrated its ability to induce an immune response without
      significant adverse effects, enabling further study on its use in paediatric
      populations.

PMID- 11228356
TI  - Enhanced induction of the IgA response in pigs by calcitriol after intramuscular
      immunization.
AB  - In this study, the immunomodulating effect of two steroid hormones namely 1,25
      dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] and dehydroepiandrosterone (DHEA) was
      examined on the antigen-specific antibody responses by intramuscular immunization
      of pigs with human serum albumin alone (HSA) or supplemented with 2 microg of
      1,25(OH)(2)D(3,) 40 microg of DHEA or the combination of both steroids.
      1,25(OH)(2)D(3) significantly enhanced the antigen-specific IgA and IgM serum
      response. Higher HSA-specific IgA titers were also found in the mucosal
      secretions (saliva, feces and nasal) of the steroid treated animals, especially
      in the 1,25(OH)(2)D(3) group. Furthermore, 1,25(OH)(2)D(3) and DHEA increased the
      number of antigen-specific IgA and IgG antibody-secreting cells in the local
      draining lymph nodes, but only low numbers were detected in lymph nodes draining
      the mucosa. DHEA decreased the IgM serum response and had a tendency to enhance
      the IgG2 and IgG serum responses. Strong and comparable IgG, IgG1 and IgG2 serum
      responses were seen in all groups. Combining both steroids did not result in a
      higher IgA serum response. On the contrary DHEA seems to neutralize the effect of
      1,25(OH)(2)D(3) on the IgA response. In conclusion, 1,25(OH)(2)D(3) significantly
      enhanced the antigen-specific IgA and IgM response in serum and the number of
      antigen-specific IgA and IgG ASC in the local draining lymph nodes following
      intramuscular immunization.

PMID- 11228357
TI  - A growth and latency compromised herpes simplex virus type 2 mutant
      (ICP10DeltaPK) has prophylactic and therapeutic protective activity in guinea
      pigs.
AB  - A growth compromised herpes simplex virus type 2 (HSV-2) mutant which is deleted
      in the PK domain of the large subunit of ribonucleotide reductase (ICP10DeltaPK)
      protects from fatal HSV-2 challenge in the mouse model (Aurelian L, Kokuba H,
      Smith CC. Vaccine potential of a Herpes Simplex Virus type 2 mutant deleted in
      the PK domain of the large subunit of ribonucleotide reductase (ICP10). Vaccine
      1999;17:1951-1963). Here we report the results of our studies with ICP10DeltaPK
      in the guinea pig model of recurrent HSV-2 disease. ICP10DeltaPK was also
      compromised for growth and disease causation in this model. It was not isolated
      from latently infected ganglia by explant co-cultivation. The proportions of
      latently infected ganglia were significantly lower for ICP10DeltaPK than HSV-2
      [3/25 (12%) and 7/10 (70%), respectively]. Similar results were obtained for the
      levels of viral DNA (8 x 10(3) and 2 x 10(5) molecules/ganglion for ICP10DeltaPK
      and HSV-2, respectively]. ICP10DeltaPK immunization caused a significant (P< or =
      0.001) decrease in the proportion of animals with primary [1/14 (6%) and 16/16
      (100%) for ICP10DeltaPK and PBS, respectively) and recurrent [1/14 (6%) and 11/14
      (79%) for ICP10DeltaPK and PBS, respectively) HSV-2 skin lesions. It also
      protected from genital HSV-2 disease [1/10 and 10/10 for ICP10DeltaPK and PBS,
      respectively] and decreased the severity of the lesions in both models.
      Quantitative PCR (Q-PCR) with primers that distinguish between HSV-2 and
      ICP10DeltaPK indicated that immunization reduced the proportion of ganglia
      positive for HSV-2 DNA [8/25 (32%) and 7/10 (70%) for ICP10DeltaPK and PBS,
      respectively) and its levels [3 x 10(3) and 2 x 10(5) molecules/ganglion for
      ICP10DeltaPK and PBS, respectively]. The proportion of HSV-2 infected animals
      with recurrent disease was also significantly (P < or = 0.001) decreased by
      immunization with ICP10DeltaPK [1/15 (7%) and 11/14 (79%) with recurrent disease
      for ICP10DeltaPK and PBS, respectively], suggesting that ICP10DeltaPK has
      prophylactic and therapeutic activity in the guinea pig.

PMID- 11228358
TI  - Enhancement of VP1-specific immune responses and protection against EMCV-K
      challenge by co-delivery of IL-12 DNA with VP1 DNA vaccine.
AB  - It has been reported that co-delivery of IL-12 DNA with a DNA vaccine further
      enhances antigen (Ag)-specific protective immunity in pathogenic challenge
      models. However, the enhancing effects of antibody by IL-12 have been
      controversial. To clarify this issue, we constructed an IL-12 expression vector,
      co-immunized IL-12 DNA with an encephalomyocarditis virus (EMCV)-D VP1 plasmid
      vaccine, and then evaluated immune modulatory effects and protection against
      lethal EMCV-K challenge. We observed that VP1-specific IgG production, as well as
      seroconversion rates, were significantly enhanced by IL-12 co-injection,
      indicating that IL-12 can enhance antibody responses in this model system. In
      particular, co-injection with VP1 plus IL-12 DNA into the same leg enhanced
      systemic Ag-specific IgG production to a significantly greater extent than either
      the separate leg injection of VP1 and IL-12 DNA or VP1 DNA vaccine alone. This
      suggests that local co-expression of IL-12 along with antigens is more important
      for enhanced antibody production. Furthermore, IgG2a isotype was significantly
      enhanced by IL-12 DNA co-injection, indicating a Th1 bias. In addition, co
      delivery of IL-12 DNA was demonstrated to enhance VP1-specific Th cell
      proliferative responses. When animals were challenged with a lethal dose of EMCV
      K, IL-12 DNA-co-immunized animals exhibited enhanced survival, as compared to VP1
      DNA vaccine alone. These studies suggest that IL-12 plays an important role in
      increasing Ag-specific Th1 type antibody and cellular responses, resulting in
      enhanced protection against lethal EMCV-K challenge.

PMID- 11228359
TI  - Capsid and RNA stabilisation of the oral polio vaccine.
AB  - The oral polio vaccine is the least stable vaccine of the common childhood
      vaccines. Two different inactivation mechanisms are responsible for the
      thermolability of the vaccine, i.e. denaturation of the viral capsid and
      degradation of the viral RNA within the capsid. Pirodavir, a capsid-binding
      compound, inhibits the viral capsid thermodenaturation. In this paper we show
      that deuterium oxide is able to stabilise the viral RNA against thermodegradation
      and that a combination of pirodavir and deuterium oxide leads to an additive
      effect indicating that both stabilisers work indeed on different inactivation
      mechanisms. Furthermore, it is shown that the variation in thermostability of the
      different vaccine strains is due to the different thermostability of their
      capsids.

PMID- 11228360
TI  - Protective responses against experimental Mycobacterium leprae infection in mice
      induced by recombinant Bacillus Calmette-Guerin over-producing three putative
      protective antigen candidates.
AB  - The components of Ag85 (Ag85A, Ag85B, and Ag85C) are putative protective antigen
      candidates against mycobacterial infection. A recombinant Mycobacterium bovis
      Bacillus Calmette-Guerin (rBCG) over-producing Ag85A, Ag85B, and MPB51
      (rBCG/BA51) was constructed. rBCG/BA51 could secrete these antigens at levels
      more than five times higher than parental BCG. Immunization of C57BL/6 and BALB/c
      mice with this rBCG reduced the multiplication of Mycobacterium leprae in the
      foot pads of both strains of mice. The inhibition by rBCG/BA51 was more evident
      than that by parental BCG.

PMID- 11228361
TI  - Vaxfectin enhances the humoral immune response to plasmid DNA-encoded antigens.
AB  - This report characterizes Vaxfectin, a novel cationic and neutral lipid
      formulation which enhances antibody responses when complexed with an antigen
      encoding plasmid DNA (pDNA). In mice, intramuscular injection of Vaxfectin
      formulated with pDNA encoding influenza nucleoprotein (NP) increased antibody
      titers up to 20-fold, to levels that could not be reached with pDNA alone. As
      little as 1 microg of pDNA formulated with Vaxfectin per muscle resulted in
      higher anti-NP titers than that obtained with 25 microg naked pDNA. The antibody
      titers in animals injected with Vaxfectin-pDNA remained higher than in the naked
      pDNA controls for at least 9 months. The enhancement in antibody titers was
      dependent on the Vaxfectin dose and was accomplished without diminishing the
      strong anti-NP cytolytic T cell response typical of pDNA-based vaccines. In
      rabbits, complexing pDNA with Vaxfectin enhanced antibody titers up to 50-fold
      with needle and syringe injections and also augmented humoral responses when
      combined with a needle-free injection device. Vaxfectin did not facilitate
      transfection and/or increase synthesis of beta-galactosidase reporter protein in
      muscle tissue. ELISPOT assays performed on bone marrow cells from vaccinated mice
      showed that Vaxfectin produced a three- to five-fold increase in the number of NP
      specific plasma cells. Thus, Vaxfectin should be a useful adjuvant for enhancing
      pDNA-based vaccinations.

PMID- 11228362
TI  - Efficacy of a live glycoprotein E-negative bovine herpesvirus 1 vaccine in cattle
      in the field.
AB  - To assess the efficacy of a live glycoprotein E-negative bovine herpesvirus 1
      (BHV1) vaccine to reduce transmission of BHV1 in cattle, a randomised, double
      blind, placebo-controlled field trial including 84 herds was conducted in the
      Netherlands. The incidence of BHV1 infections during 17 months was monitored by
      detecting antibodies against BHV1 glycoprotein E. In the placebo-treated group
      214 seroconversions in 3985 paired sera, and in the vaccinated group 67
      seroconversions in 3601 paired sera were detected. Based on these data, the
      transmission ratio R(0) was estimated for each treatment, using the maximum
      likelihood approach and the martingale approach. In placebo-treated herds R(0)
      was 2.5 (CI 1.4-3.1) using maximum likelihood and 2.8 (S.E. 0.4) using the
      martingale approach. In the vaccinated group these estimations were 1.2 (CI 0.5
      1.5) and 1.5 (S.E. 0.4) respectively. The vaccinated and placebo-treated group
      differed significantly in transmission of BHV1. These results suggest that the
      use of this live gE-negative BHV1 vaccine will reduce the incidence and
      transmission of BHV1 infections in the field.

PMID- 11228363
TI  - Immunization with recombinant Streptococcus gordonii expressing tetanus toxin
      fragment C confers protection from lethal challenge in mice.
AB  - Tetanus toxin fragment C (TTFC) was expressed on the surface of the vaccine
      vector Streptococcus gordonii, a Gram-positive commensal bacterium of the human
      oral cavity. The immunogenicity of recombinant S. gordonii expressing TTFC was
      assayed in mice immunized by the parenteral and mucosal routes. High serum TTFC
      specific IgG responses were induced in both BALB/c and C57BL/6 mice immunized
      subcutaneously. A total of 82% of vaccinated BALB/c mice were protected from the
      lethal challenge with 50 LD(50) of tetanus toxin (TT) and a direct correlation
      between the serum TTFC-specific IgG concentration and survival time of
      unprotected animals was observed. Intranasal immunization of BALB/c mice was also
      effective in inducing TTFC-specific serum IgG and local IgA in lung washes.
      Furthermore, 38% of animals immunized intranasally were protected from the lethal
      challenge with 10 LD(50) of TT while all control animals died within 24 h.
      Analysis of the serum IgG subclasses showed that the IgG1 subclass was
      predominant after parenteral immunization in BALB/c mice (IgG1/IgG2a ratio
      congruent with6) while following mucosal immunization a mixed IgG1 and IgG2a
      pattern (IgG1/IgG2a ratio congruent with1) was observed. These data show that
      TTFC expressed on the surface of S. gordonii is immunogenic by the subcutaneous
      and mucosal routes and the immune response induced is capable of conferring
      protection from the lethal challenge with TT.

PMID- 11228364
TI  - Protection against Bordetella pertussis infection following parenteral or oral
      immunization with antigens entrapped in biodegradable particles: effect of
      formulation and route of immunization on induction of Th1 and Th2 cells.
AB  - The immunogenicity and protective efficacy of systemically and orally delivered
      pertussis antigens entrapped in either microparticle poly-lactide-co-glycolide
      (PLG) or nanoparticle PLG formulations were evaluated in a murine respiratory
      challenge model for infection with Bordetella pertussis. The results demonstrate
      that immunization with two parenteral doses of 1 microg or three oral doses of
      100 microg of pertussis toxoid (PTd) and filamentous haemagglutinin (FHA)
      encapsulated in PLG conferred a high level of protection against B. pertussis
      challenge. Furthermore protection could be generated with a single parenteral
      immunization with a combined microparticle and nanoparticle formulation. However,
      the route of immunization and the size of the particles affected the type of T
      cell response induced. Parenteral immunization with PTd and FHA entrapped in PLG
      microparticles elicits a potent type 1 T cell response and potent antibody
      response when given by the intraperitoneal (i.p.) or intramuscular (i.m.) route.
      In contrast, nanoparticle formulations favoured the induction of Th2 cells.

PMID- 11228365
TI  - Measles antibody responses after early two dose trials in Guinea-Bissau with
      Edmonston-Zagreb and Schwarz standard-titre measles vaccine: better antibody
      increase from booster dose of the Edmonston-Zagreb vaccine.
AB  - In Guinea-Bissau, children were randomised at 6 months of age to receive either
      two doses of standard-titre measles vaccine at 6 and 9 months of age or an
      inactivated polio vaccine at 6 months and standard-titre measles vaccine at 9
      months of age. During the first 5 months, children received Edmonston-Zagreb (EZ)
      vaccine and during the following 11 months, the Schwarz (SW) vaccine. Five
      percent of the mothers, 74% of children at 6 months of age, and 92% of
      unvaccinated children at 9 months of age had unprotective levels (<125 mIU/ml) of
      measles antibodies. Among children receiving EZ vaccine, 1% were unprotected at
      18 months of age after either two (3/240) or one (3/211) doses of vaccine, the
      geometric mean measles antibody titre (GMT) being approximately 1550 mIU/ml in
      both groups. Among those receiving SW vaccine 9% (34/365) and 3% (9/310) were
      unprotected at 18 months of age in the two-dose and the one-dose groups (RR =
      3.21 (95% confidence interval (CI) 1.56-6.58)), respectively. The GMT was higher
      after one dose of SW vaccine at 9 months of age (2491 mIU/ml) than after two
      doses of SW vaccine (1125 mIU) (P < 0.001). In the EZ vaccine group, there was no
      significant difference in antibody level for children vaccinated in the presence
      of high or low levels of maternal antibodies, whereas there was a marked
      difference in the SW group. The second EZ vaccine induced a significant antibody
      increase between 9 months of age (1191 mIU) and 18 months of age (1602 mIU,
      P=0.011), whereas antibody levels tended to decline from 9 months (1243 mIU) to
      18 months of age (998 mIU, P = 0.124) after the second dose of SW vaccine.
      Conclusively, after two doses of EZ measles vaccine more children were protected
      at 18 months of age than after two doses of SW. One dose of SW provided the
      highest antibody response, but a higher proportion of unprotected than one or two
      doses of EZ. The EZ vaccine was less sensitive to maternal antibodies, and able
      to increase the antibody response by revaccination, while the second SW vaccine
      resulted in an unchanged or lower antibody response.

PMID- 11228366
TI  - Induction of immunological memory in baboons primed with DNA vaccine as neonates.
AB  - DNA immunization is a potential vaccination strategy for neonates and infants. We
      tested the ability of a prototype DNA vaccine against influenza virus to prime
      lasting immunity when administered to newborn non-human primates. Neonatal DNA
      vaccination triggered virus-specific and neutralizing antibodies of titers and
      persistence depending on the vaccine dose. Subsequent exposure to influenza
      virus, revealed significantly increased recall responses in the baboons
      vaccinated with DNA during the neonatal stage. The humoral and cellular responses
      were enhanced in the baboons primed with DNA vaccine as neonates. Thus, neonatal
      DNA vaccination of non-human primates triggered immune memory that persisted
      beyond infancy.

PMID- 11228367
TI  - Immune reactions of CD4- and CD8-positive T cell subpopulations in spleen and
      lymph nodes of guinea pigs after vaccination with Bacillus Calmette Guerin.
AB  - Vaccination of guinea pigs with Mycobacterium bovis BCG confers partial
      resistance against infection with Mycobacterium tuberculosis. Induction of
      immunity is associated with a strong T cell response. The reactions of the
      cytotoxic and helper T lymphocyte subsets after BCG vaccination were analyzed by
      cytofluorometry and in functional tests. The relative number of CD8(+) T cells in
      the spleen increased substantially after injection of BCG. In vitro restimulation
      after immunization induced a strong proliferative response but no cytotoxic
      reactions of CD8(+) T cells against BCG-infected macrophages. A specific
      induction of IFN-gamma and RANTES mRNA was observed after vaccination
      particularly in CD8(+) but not in CD4(+) T cells of the lymph nodes.

PMID- 11228368
TI  - Semliki Forest virus-based vaccines: persistence, distribution and pathological
      analysis in two animal systems.
AB  - This study has examined the persistence, distribution and pathological changes
      following intramuscular administration of Semliki Forest virus (SFV) vaccine
      vectors in mice and chickens. Administration of recombinant SFV RNA particles
      showed persistence at the injection site of mice up to 7 days, transient
      detection in secondary lymphoid organs and no dissemination to distal sites. In
      contrast, administration of a layered SFV DNA/RNA vector and a conventional
      standard naked DNA vector resulted in long-term persistence at the injection
      site, plasmid DNA being detected at 8 months post-inoculation in mice. Plasmid
      DNA was found distributed throughout the body, and tissues distal from the site
      of injection were positive up to 3 months. A similar pattern was observed in
      chickens. Mild pathological changes were observed at the injection site only, and
      plasmid DNA or recombinant RNA was not detected in mouse foetuses. These findings
      indicate that SFV-based vectors have the potential to be developed as safe
      vaccines.

PMID- 11228369
TI  - Development of a new method for the quantitative analysis of the extracellular
      polysaccharide of Neisseria meningitidis serogroup A by use of high-performance
      anion-exchange chromatography with pulsed-amperometric detection.
AB  - A new method for the quantitative determination of Neisseria meningitidis group A
      (MenA) capsular polysaccharide (CPS) has been developed. The method is based on
      trifluoracetic acid (TFA) hydrolysis of the CPS (2 M at 80 degrees C for 3 h),
      followed by chromatographic separation and quantification of the liberated
      mannosamine-6-phosphate from the area of the peak obtained using an IonPac AS11
      column coupled to the sensitive pulsed amperometric detector ED40. The highly
      selective nature of this method circumvents the interference problems associated
      with the classical method based on a colorimetric assay for phosphorus. Provided
      that suitable hydrolysis conditions can be found, this chromatographic approach
      might be applicable to the quantification of other bacterial antigens containing
      phosphorylated sugars such as meningococcal groups H, L, X and Z, and
      pneumococcal serotypes 6, 10A and 19.

PMID- 11228370
TI  - Serological and epidemiological effects and influence factors of primary
      immunization with current live attenuated measles vaccine (Hu191) among infants
      aged 6-15 months.
AB  - A study of the serological and epidemiological effects of primary immunization
      with current live attenuated measles vaccine (Hu191) among 503 children aged 6-15
      months, was conducted in Jingzhou, Hubei province, China from 1991 to 1998. The
      results showed that the positive conversion rate of measles IgG was 91.65%,
      geometric mean titer (GMT) was 1:266.74 and its ratio reaching protective titer
      was 46.52% at 1 month after first immunization. As time goes on, the above
      mentioned indexes reduced rapidly. Short-term and long-term efficacy of 0.2, 0.3
      and 0.5 ml measles vaccine was similar. The positive conversion rate, GMT and
      ratio of protective titer of IgG of different potency measles vaccine were not
      significantly different, however, latter two indexes showed a tendency to
      increase gradually with the rise of vaccine potency. The age for primary
      immunization was a main factor influencing immune response to measles vaccine.
      Immune efficacy of 6 months old group by primary vaccination was significantly
      lower than those of > or = 8 months old group. The result indicated it is
      practicable that infant aged 8 months be vaccinated with measles vaccine in
      China. Twenty-nine suspected measles cases were reported, out of them, 26 cases
      were negated in time from December 1991 to November 1998. The study showed that
      the short-term positive conversion rate of the enzyme immune assay IgG antibody
      of the Hu191 is higher, but its serological endurance isn't ideal, and its
      epidemiological effect should be evaluated further.

PMID- 11228371
TI  - Surveillance of infectious diseases in the Italian military as pre-requisite for
      tailored vaccination programme.
AB  - Surveillance and control of infectious diseases in the Italian military include
      prompt reporting of all occurring cases and prophylaxis through compulsory
      vaccination practices. The last mandatory immunisation programme in the Italian
      military was launched in 1998 (more than 10 years after the previous programme
      was introduced in 1986-1987) and it was planned according to the epidemiological
      data herein reported. The incidence rates (number of cases x 100000 subjects) of
      infectious diseases notified during the period 1976-1980 were compared with the
      corresponding figures notified 15 years later (1991-1995). An increase of three
      airborne-transmitted viral diseases--varicella, rubella and measles-
      counterbalanced by a decrease of other infectious diseases, such as mumps,
      typhoid fever, tuberculosis, viral hepatitis, scabies, syphilis and gonorrhea,
      was observed. This may be related to improvements in the general hygienic
      conditions and more responsible sexual behaviour among Italian military recruits.
      Moreover, incidence rates of cases notified in the military were compared with
      those notified in the general population of the same sex- and similar age-range
      (15-24 years) over a 12-year period (1986-1997), to monitor the epidemiological
      situation in relation to (a) potential risk factors specifically linked to
      military life and (b) protective effects induced by specific vaccinations.
      Airborne-transmitted viral diseases, such as varicella, rubella, measles and
      mumps--which are usually underreported among civilians--show higher incidence
      rates in the military. Meningococcal meningitis shows higher incidence rates in
      the military in 1986 and 1987 (before the introduction of mandatory specific
      vaccination) as well as in 1995-1997 (main etiologic agent N. meningitidis
      serogroup B); similar rates were instead observed in the other years. Incidence
      rates for typhoid fever are generally lower in the military, despite the
      community life, probably reflecting the protective efficacy of specific vaccine.
      Hepatitis A and B show similar rates between military and civilian population.
      Finally, pulmonary tuberculosis generally shows higher rates in the military.
      These data therefore allow the conclusion that the only infectious diseases, for
      which possible risk factors in the military life may be hypothesised, seem to be
      meningococcal meningitis and perhaps pulmonary tuberculosis. Epidemiological
      surveillance of infectious diseases in the military as a pre-requisite for
      appropriate public health intervention strategy represents a good model to be
      followed also in larger contexts.

PMID- 11228372
TI  - Microparticle-mediated RNA immunization against bovine viral diarrhea virus.
AB  - Infectious transcripts from the full-length infectious clone of the NADL strain
      of bovine viral diarrhea virus (BVDV) were used to vaccinate cattle and sheep
      against BVDV. In vitro synthesized RNA delivered by microparticle bombardment
      with a Helios Gene Gun initiated replication of BVDV and consequently induced
      humoral immunity against type I BVDV (serum neutralization titers, SNT > 2(12))
      and type II BVDV (SNT > 2(7)). The quality and long-term stability of the RNA
      carrier complexes was assessed by microparticle bombardment of tissue culture
      monolayers. The RNA cartridges were found to be stable for at least 8 months upon
      storage. This is the first report on successful RNA vaccination of large
      ruminants.

PMID- 11228373
TI  - IL-12-mediated increases in protection elicited by pneumococcal and meningococcal
      conjugate vaccines.
AB  - Interleukin-12 (IL-12) may be a beneficial adjuvant for augmenting vaccine
      efficacy against encapsulated bacteria such as Streptococcus pneumoniae and
      Neisseria meningitidis since it can stimulate production of interferon-gamma (IFN
      gamma) and secretion of antibody isotypes that are efficient at mediating
      complement fixation and opsonophagocytosis. In this study, we demonstrate the
      ability of IL-12 to enhance murine antibody responses, particularly IgG2a levels,
      to both pneumococcal and meningococcal conjugate vaccines. Transfer of immune
      serum from mice immunized with the meningococcal conjugate vaccine and IL-12
      resulted in increased survival times, whereas transfer of serum from mice
      immunized with the pneumococcal conjugate and IL-12 resulted in protection from
      death upon bacterial challenge. Although treatment with vaccine and IL-12
      increased levels of IFN-gamma mRNA, IL-12-mediated enhancement of antibody
      responses still occurred in IFN-gamma(-/-) mice. The results demonstrate the
      effectiveness of IL-12 as an adjuvant for polysaccharide conjugate vaccines,
      especially the pneumococcal conjugate vaccine.

PMID- 11228374
TI  - Development of therapeutic vaccines by direct modification of cell membranes from
      surgically removed human tumor tissue with immunostimulatory molecules.
AB  - The addition of immunostimulatory molecules to tumor cells has been proposed as a
      potentially useful strategy to induce anti-tumor immunity. In this report we have
      investigated the application of using isolated tumor membranes modified by
      transfer of a glycosyl-phosphatidylinositol (GPI)-anchored form of the
      costimulatory molecule, B7-1 (CD80), as a cell free cancer vaccine for clinical
      use. Isolated tumor cell membranes were prepared from established tumor cell
      lines and the optimum conditions necessary for modification and clinical
      application were determined. GPI-B7-1 transferred optimally onto isolated human
      tumor membranes at physiological temperature (37 degrees C) in a dose dependent
      manner. Transfer of GPI-B7-1 to isolated membranes resulted in stable expression
      and costimulatory function. These modified membranes could be stored for repeated
      immunizations while retaining expression of GPI-B7-1. Critically, isolated tumor
      membranes, prepared directly from surgically removed human tumor tissue, could be
      modified by GPI-B7-1 and costimulate T cells. Finally, membranes isolated from
      tumor tissue expressed MHC class II, unlike the cell line established in vitro
      from the same patient. This novel approach to express immunostimulatory molecules
      on isolated membranes derived from a patient's tumor tissue will make the
      preparation of autologous therapeutic cancer vaccines available to patients from
      which tumor cell lines can not be established.

PMID- 11228375
TI  - DNA vaccination in mice using HIV-1 nef, rev and tat genes in self-replicating
      pBN-vector.
AB  - The immunogenicity of a self-replicating DNA-vector containing HIV-1 nef gene
      (pBN-Nef) was characterized using various DNA delivery methods. In addition, gene
      gun immunisation was used for assessing immunogenicity of two other HIV-1 genes
      (rev and tat) given in the same vector. The pBN-Nef was the most immunogenic
      raising both humoral and cell-mediated immune responses in mice; these responses
      lasted for up to six months. The pBN-Nef vector was immunogenic also when given
      intramuscularly or intradermally. The pBN-Rev construct did not elicit humoral
      responses but did elicit proliferative as well as CTL-response against the
      corresponding protein. The pBN-Tat was a poor immunogen in all respects. The
      antibodies elicited with various DNA delivery methods belonged to different
      antibody subclasses; however, two main epitopes in Nef were frequently recognized
      by all of them.

PMID- 11228376
TI  - Monophosphoryl lipid A adjuvant reverses a principal histologic parameter of
      formalin-inactivated respiratory syncytial virus vaccine-induced disease.
AB  - The mechanisms by which administration of a formalin-inactivated respiratory
      syncytial virus vaccine resulted in enhanced disease among children after they
      later became naturally infected with the virus remains largely undefined. After
      immunization and live virus challenge, the cotton rat demonstrated the
      histopathologic marker of the enhanced disease, polymorphonuclear leukocyte
      infiltration of lung alveolar spaces. We now report that immunization with
      formalin-inactivated vaccine formulated with the adjuvant, 3-deacylated
      monophosphoryl lipid A, dramatically reduces or eliminates the polymorphonuclear
      leukocyte infiltration within the alveoli of cotton rats post-challenge. We
      suggest, that this or similar adjuvants may be beneficial components of candidate
      non-replicating respiratory syncytial virus vaccines, whose development has been
      hampered by safety concerns.

PMID- 11228377
TI  - Antibody-response to three recombinant hepatitis B vaccines: comparative
      evaluation of multicenter travel-clinic based experience.
AB  - The immunogenicity of three currently used hepatitis B vaccines was compared in
      an unselected study population in an every day travel clinical setting. Five
      hundred and eighteen vaccinees received Engerix-B (EB), 990 received Twinrix
      (TWX), and 366 were immunised with Gen-HB-Vax (GHB). Overall, 88.6% of the
      vaccinees, tested within the first 6 months after completion of the vaccination
      series, developed protective levels of anti-HBs (> or = 10 mIU/ml). However, GHB
      recipients showed significantly lower seroprotection rates (SPR) than EB and TWX
      recipients (79.3% vs. 87.7% vs. 92.3%, P < 0.000001). GMTs for anti-HBs, tested
      within 6 months after the third vaccination, showed the lowest results in the GHB
      group, followed by EB and TWX (142 vs. 523 vs. 1008 mIU/ml, P < 0.000001). TWX
      vaccinees, however, showing a higher antibody decline rate than EB recipients
      within the first years after completion of the full immunisation course (30% vs.
      25%; P = 0.0538). This study confirms an overall good immune response to the 20
      microg-dose vaccine, in the course of a regular clinical setting. The significant
      difference in SPRs and GMTs to the 10 microg-dose vaccine, however, may influence
      future immunisation practices for the elderly.

PMID- 11228378
TI  - Nasal immunization with E. coli verotoxin 1 (VT1)-B subunit and a nontoxic mutant
      of cholera toxin elicits serum neutralizing antibodies.
AB  - Escherichia coli O157:H7 produces two forms of verotoxin (VT), VT1 and VT2, which
      cause hemorrhagic colitis with development, in some cases, of hemolytic uremic
      syndrome. These toxins consist of an enzymatically active A subunit and pentamers
      of B subunit responsible for their binding to host cells. We used the secretion
      expression system of Bacillus brevis to produce recombinant VT1B and VT2B. The
      secreted B subunits were purified and sequenced to verify their structure.
      Receptor-binding showed that rVT1B but not rVT2B bound to Gb3-receptor. When mice
      were nasally immunized with rVT1B or rVT2B together with a nontoxic mutant of
      cholera toxin (mCT) or native cholera toxin (nCT) as adjuvants, serum IgG and
      mucosal IgA antibody responses to VT1B were induced. The VT1B-specific antibodies
      prevented VT1B binding to its Gb3 receptor. In contrast, poor serum and no
      mucosal VT2B-specific antibodies but brisk CTB-specific antibody responses were
      induced by nasal immunization with rVT2B in the presence of mCT or nCT. These
      results show that nasal immunization with rVTB and mCT as a nontoxic mucosal
      adjuvant is an effective regimen for the induction of VT1B but not VT2B antibody
      responses which inhibit VT1B binding to Gb3 receptor.

PMID- 11228379
TI  - Effectiveness and safety of mutant Escherichia coli heat-labile enterotoxin (LT
      H44A) as an adjuvant for nasal influenza vaccine.
AB  - The effectiveness and safety of mutant Escherichia coli heat-labile enterotoxin,
      LT H44A (His to Arg substitution at position 44 from the N-terminus of the A1
      fragment of the A subunit) as an adjuvant for nasal influenza vaccine were
      examined. (1) When 0.2 microg of LT H44A, together with 0.2 microg of influenza
      A/PR/8/34 virus (PR8, H1N1) vaccine, was administered intranasally into BALB/c
      mice (twice, 4 weeks apart), anti-PR8 hemagglutinin (HA) IgA and IgG antibody
      (Ab) responses were induced at levels that were sufficient to provide either
      complete protection against infection with a small volume of PR8 virus suspension
      or partial protection against infection with a lethal dose of the suspension. The
      dose of the mutant LT and vaccine used here (0.2 microg/ 20 g doses mouse)
      corresponded to the estimated dose per person, i.e. 0.1 mg/10 kg body weight. (2)
      Using these vaccination conditions, no additional total IgE Ab responses were
      induced. (3) The mutant was confirmed to be less toxic than the native LT when
      the toxicity was analyzed either using Y1 adrenal cells in vitro (1/483 EC(50))
      or by an ileal loop test. (4) One hundred micrograms of the mutant, administered
      intranasally or intraperitoneally into guinea-pigs (Heartley strain, 0.3-0.4 kg),
      caused no body-weight changes 7 days after administration, although 100 microg of
      the native LT administered intraperitoneally caused death in all guinea-pigs due
      to diarrhea within 2 days. The intranasal administration of 100 microg of the
      mutant resulted in almost no pathological changes in the nasal mucosa 3 days
      after administration. These results suggest that LT H44A, which can be produced
      in high yields in an E. coli culture (about 5 mg/l), could be used as one of the
      effective and safe adjuvants for nasal influenza vaccine in humans.

PMID- 11228380
TI  - QS-21 promotes an adjuvant effect allowing for reduced antigen dose during HIV-1
      envelope subunit immunization in humans.
AB  - Three separate studies were undertaken in HIV-1 uninfected persons to determine
      if the adjuvant QS-21 improves the magnitude or kinetics of immune responses
      induced by recombinant soluble gp120 HIV-1(MN) protein (rsgp120) immunization.
      The QS-21 was administered at two doses (50 and 100 microg), either alone or in
      combination with aluminum hydroxide (600 microg). At the highest doses of rsgp120
      (100, 300, and 600 microg), QS-21 exerted no significant effect on either binding
      or neutralizing antibody titers. Antibody binding and neutralizing responses fell
      dramatically when rsgp120, formulated with alum alone, was given at low doses (3
      and 30 microg). In contrast, antibody responses similar in titer to those in the
      high dose antigen groups were induced with the low dose rsgp120 formulated with
      QS-21. In addition, the lymphocyte proliferation and delayed type
      hypersensitivity skin testing were superior in the QS-21 recipients compared with
      the alum recipients at the low antigen doses. Moderate to severe pain was
      observed in majority of the volunteers receiving QS-21 formulations, and
      vasovagal episodes and hypertension were not infrequent. Thus, the use of QS-21
      may provide a means to reduce the dose of a soluble protein immunogen.

PMID- 11228381
TI  - Immunopotentiation of Staphylococcus aureus type 5 capsular polysaccharide co
      entrapped in liposomes with alpha-toxin.
AB  - Immunopotentiation of Staphylococcus aureus type 5 capsular polysaccharide (CP5)
      by use of liposomes as an alternative to protein-polysaccharide conjugates was
      investigated. Mice were immunized twice with cationic liposomes containing CP5
      alone or CP5 co-entrapped with alpha-toxin or heat-detoxified alpha-toxin.
      Immunogenicity of these different antigens was compared with CP5-alpha-toxin
      conjugates. Antibodies against CP5 were elicited in mice immunized with
      conjugates or liposomes containing co-entrapped CP5 and alpha-toxin. Liposomes
      containing CP5 alone or co-entrapped CP5 and alpha-toxoid failed to induce
      antibodies against CP5. All the preparations entailed an antibody response
      against alpha-toxin and highest antibody and neutralizing activity titers were
      obtained with liposomes. These results show that liposomes can be used to
      immunopotentiate CP5, however, a co-incorporated protein able to insert lipids
      bilayers is probably required.

PMID- 11228382
TI  - Immunogenicity and safety of autoclaved Leishmania major plus BCG vaccine in
      healthy Sudanese volunteers.
AB  - In a longitudinal study in the epidemiology of Leishmania donovani infection in
      an endemic focus in eastern Sudan, we observed that previous exposure or
      infection with Leishmania major appeared to protect against visceral
      leishmaniasis caused by L. donovani. We therefore conducted a study to test the
      safety and immunogenicity of a vaccine consisting of autoclaved L. major (ALM)
      plus BCG in inducing protection in vaccinated individuals. Leishmanin-negative
      healthy Sudanese volunteers were enrolled in the study and were divided into
      three groups: group (A) received ALM+BCG, group (B) received BCG alone, and group
      (C) received the vaccine diluent. The subjects were examined for their clinical
      and immunological responses before intervention, following intervention and 6-8
      weeks after vaccination. Vaccinated subjects (group A) developed localized
      reactions at the sites of vaccine inoculation that ulcerated and healed within 4
      6 weeks; 61.6% of them converted to leishmanin reactive following vaccination.
      Only one subject in group (C) became leishmanin-positive. A total 76.9% of the
      vaccinated volunteers in group (A) produced significant levels of interferon
      gamma in response to L. major antigen. The vaccine produced significant cellular
      immune responses that may protect against natural challenge. None of the groups
      had systemic reactions and all the reactions observed in the vaccinated group
      were comparable with the BCG-vaccinated group.

PMID- 11228383
TI  - The suitability of the 'emergency' foot-and-mouth disease antigens held by the
      International Vaccine Bank within a global context.
AB  - The International Vaccine Bank (IVB) based at the Institute of Animal Health
      (IAH) in Pirbright, United Kingdom (UK), routinely monitors the suitability of
      the currently held strains of foot-and-mouth disease (FMD) vaccine virus, in
      anticipation that vaccine may be required to control FMD outbreaks that pose a
      threat to member countries. Using primarily the two-dimensional micro
      neutralisation test (VNT), bovine polyclonal sera raised against each of the
      seven current 'emergency' antigens were utilised to measure the relationship of
      IVB stocks to selected field isolates. The 'O' serotypes, Manisa and Lausanne,
      exhibited adequate levels of cross-protection against most of the type 'O' field
      isolates examined. A(22) Iraq 24/64 showed the broadest spectrum of reactivity
      against the type 'A' field isolates examined and was supplemented by A(15)
      Thailand 1/60. Some type 'Asia1' field isolates, particularly those from South
      East Asia, showed antigenic difference to the Asia1 India 8/79 vaccine strain by
      VNT, but in-vivo testing in the guinea pig model indicated this to be
      insignificant. The only 'C' serotype representative, C(1) Oberbayern, may be one
      of the least antigenically diverse of the current portfolio of bank antigens.
      Comparison of the serological and sequence data shows that despite significant
      genetic variation between the field isolates examined the antigens held by the
      IVB should still prove efficacious in the field.

PMID- 11228384
TI  - Potency of clinical group B streptococcal conjugate vaccines.
AB  - The potency of clinical group B streptococcal (GBS) capsular polysaccharide
      protein conjugate vaccines has been assessed with use of a mouse maternal
      vaccination-neonatal pup challenge model of GBS disease. Two of the three
      conjugated GBS vaccines bottled as liquid preparations showed a potency reduction
      from 100% to < or = 50% in 3 years; whereas all six vaccines bottled as
      lyophilized preparations with sucrose excipient exhibited no loss of potency
      during the same span of time. A reconstituted GBS conjugate vaccine remained
      potent and antigenically intact after 31 days' storage at 2-8 degrees C. These
      data suggest that lyophilization in the presence of sucrose extends the potency
      of GBS conjugate vaccines.

PMID- 11228386
TI  - The economics of vaccinating restaurant workers against hepatitis A.
AB  - The economics of vaccinating restaurant workers against hepatitis A were studied
      using Monte Carlo simulation models, one with a restaurant-owner perspective, and
      one with a societal perspective. The restaurant model allowed for a different
      size, number of employees and employee turnover rate. Benefits were the avoidance
      of loss of business (including the possibility of bankruptcy) after publicity
      linking the restaurant to an outbreak associated with a case of hepatitis A in a
      food handler. Additional benefits in the societal model included reductions in
      costs of food handler-associated cases of hepatitis A. The outcome used was Net
      Present Value (NPV), allowing comparison between models. Regardless of the cost
      of vaccination ($50-140/employee), for a restauranteur to ensure that all
      employees were vaccinated at all times substantial costs were involved (i.e.
      negative NPV). Even a 75% probability of bankruptcy still resulted in negative
      NPVs at the 95th percentiles. For society, vaccination was only cost-saving (i.e.
      positive NPV) if done only during epidemics and if it cost < $20/employee.
      Vaccinating restaurant employees is unlikely to be economical from either the
      restaurant owner or the societal perspective, even during hepatitis A epidemics.

PMID- 11228385
TI  - A combined liquid Hib (PRP-OMPC), hepatitis B, diphtheria, tetanus and whole-cell
      pertussis vaccine: controlled studies of immunogenicity and reactogenicity.
AB  - We evaluated the immunogenicity and reactogenicity of a new liquid pentavalent
      combination vaccine, which incorporates a diphtheria, tetanus and whole-cell
      pertussis vaccine (DTP) with Hib (PRP-OMPC) and hepatitis B vaccine (HB), in a
      series of three studies involving 2156 infants. The vaccination schedule was 2,
      4, 6 and 18 months for all studies. In addition, subjects in the third study also
      received a dose of monovalent hepatitis B vaccine at birth. The principal study
      was a randomised double blind trial of two separate, but concurrently
      administered vaccines in each of three groups: pentavalent vaccine [DTP-Hib-HB]
      plus placebo (Group A, n=619); quadrivalent vaccine [DTP-HB] plus Hib vaccine
      (Group B, n=620); and bivalent vaccine [Hib-HB] plus DTP (Group C, n=226). The
      second study (Group D, n=231) was an open trial of three separate, but
      concurrently administered licensed control vaccines (DTP, Hib and HB). The third
      study (Group E, n=460) administered a dose of monovalent hepatitis B vaccine at
      birth followed by pentavalent vaccine as for Group A. Subjects were bled prior to
      the 2- and 18-month vaccinations, and a month after the 6- and 18-month
      vaccinations. A diary card was used to record subject temperatures and other
      systemic and local clinical signs for 7 days after each vaccination. The
      pentavalent vaccine, whether or not preceded by a birth dose of hepatitis B
      vaccine, was generally well tolerated at all administration times, and had a
      reactogenicity profile similar to that observed for licensed vaccine controls.
      Diphtheria and tetanus antibody levels were substantially above protective levels
      in all study groups. The anti-HBs responses (% > or = 10 mIU/ml) following the 6
      month dose of vaccines were, respectively, for Groups A-E: 83.2, 91.7, 96.5, 98.8
      and 93.9%, and following the 18-month doses: 87.9, 97.5, 98.8, 98.8 and 92.8%.
      Anti-PRP responses (% > or = 1.0 microg/ml) following the 6-month dose for Groups
      A-D were 86.0, 90.5, 91.2, and 74.4%, and after the 18-month dose for Groups A-E
      were 97.3, 98.3, 98.1, 97.0, and 99.5%. Consistently higher geometric mean titres
      (GMTs) for pertussis antibodies to agglutinogens (Agg2, Agg3) and pertactin were
      recorded for the pentavalent vaccine compared to the licensed control vaccine,
      though they were somewhat lower for pertussigen (PT). Except for the hepatitis B
      response, antibody responses induced by the pentavalent vaccine to all antigens
      with a schedule commencing at 2 months of age and completed at 18 months were
      equivalent to responses to the same antigens induced by the separate, but
      concurrently administered licensed control vaccines. A regimen of a birth dose of
      hepatitis B vaccine followed by pentavalent vaccine at 2, 4, 6 and 18 months was
      not countered by any clinically significant decrease in seroresponses.

PMID- 11228387
TI  - Identification of substrains of BCG vaccine using multiplex PCR.
AB  - Current methods for determining the identity of substrains of Mycobacterium bovis
      BCG (BCG) vaccine are labour intensive, or provide only limited substrain
      differentiation. In this paper we describe a multiplex PCR that distinguishes
      between M. tuberculosis (TB) and M. bovis and the non-pathogenic BCG strain, and
      also subdivides the BCG vaccine substrains investigated into seven distinct
      fingerprints based on six target regions in the DNA. This test is specific,
      rapid, reproducible and portable and is proposed as a novel test for BCG vaccine
      control. It offers substantial advantages over the methods currently in use.
      Using this test we have characterised a number of commercial BCG vaccines.

PMID- 11228388
TI  - Immune responses and protection against foot-and-mouth disease virus (FMDV)
      challenge in swine vaccinated with adenovirus-FMDV constructs.
AB  - A replication-defective adenovirus 5 encoding foot-and-mouth disease virus (FMDV)
      capsid and 3C proteinase coding regions (Ad5-FMDV3CWT) was used to vaccinate
      swine. A single inoculation utilizing 1 x 10(8) plaque forming units (pfu) or an
      inoculation of 1 x 10(8) followed by a boost of 5 x 10(8) pfu Ad5-FMDV3CWT were
      tested, along with an inoculation and boost using an adenovirus encoding the FMDV
      capsid coding region and an inactive form of the 3C proteinase (Ad5-FMDV3CMUT).
      Sera collected from these animals were examined for the presence of FMDV-specific
      antibodies using immunoprecipitation, neutralization, and ELISA assays specific
      for IgM, IgG1 and IgG2. Efficacy studies were performed by placing the vaccinated
      swine in contact with an FMDV-infected swine and monitoring for signs of disease
      and changes in serum antibody levels. Ad5-FMDV3CMUT, which is unable to produce
      FMDV capsid structures, did not elicit FMDV-neutralizing antibodies or protect
      against FMD. Single inoculation with Ad5-FMDV3CWT generated FMDV-specific
      neutralizing antibodies, and reduced clinical signs in challenged swine, but
      failed to completely protect the majority of swine from FMD. Swine which received
      a primary vaccination with Ad5-FMDV3CWT followed by the boost at 4 weeks
      generated high levels of FMDV-neutralizing antibodies resulting in complete
      protection of five of the six swine and limited disease in the remaining animal.
      Increased efficacy of the two-dose regimen was associated with heightened levels
      of FMDV-specific IgG1 and IgG2 antibodies.

PMID- 11228389
TI  - Plant-derived measles virus hemagglutinin protein induces neutralizing antibodies
      in mice.
AB  - Measles remains a significant problem in both the developed and developing world,
      and new measles vaccination strategies need to be developed. This paper examines
      the strategy of utilizing transgenic plants expressing a measles antigen for the
      development of an oral sub-unit measles vaccine. A 1.8 kb fragment encompassing
      the coding region of the measles virus hemagglutinin (H) protein was cloned into
      a plant expression cassette. Three different expression constructs were tested:
      pBinH (H gene alone), pBinH/KDEL (addition of a C-terminal endoplasmic reticulum
      retention sequence SEKDEL) and pBinSP/H/KDEL (further addition of an authentic N
      terminal plant signal peptide). The highest levels of recombinant H protein
      production were observed in plants transformed with pBinH/KDEL. Mice inoculated
      intraperitoneally with transgenic plant derived recombinant H protein produced
      serum anti-H protein antibodies that neutralized the measles virus (MV) in vitro.
      Mice gavaged with transgenic tobacco leaf extracts also developed serum H protein
      specific antibodies with neutralizing activity against MV in vitro. These results
      indicate that the plant-derived measles H protein is immunogenic when
      administered orally and that, with further development, oral vaccination
      utilizing transgenic plants may become a viable approach to measles vaccine
      development.

PMID- 11228390
TI  - Establishment of gene-vaccinated skin grafting against Toxoplasma gondii
      infection in mice.
AB  - Vaccine effects of in vivo gene-vaccinated skin graft were evaluated against
      Toxoplasma gondii (T. gondii) infection. By using a gene gun, cDNA coding T.
      gondii SAG1 molecule was intracutaneously vaccinated into C57BL/6 (B6; a
      susceptible strain), BALB/c (a resistant strain) and (C57BL/6 x BALB/c) F1 (CBF1)
      mice, and the gene-vaccinated skin of these strains was transplanted to CBF1
      mice. Regarding the antibody production against SAG1, CBF1-recipient mice
      transplanted with the SAG1 gene-vaccinated B6 skin were high responders, whereas
      CBF1 mice skin grafted with vaccinated skin of both BALB/c and CBF1 mice were low
      responders. The donor-derived LC/DC migrated to the draining lymph nodes of the
      recipients from the skin graft within 3 days. The vaccine effect against T.
      gondii challenge infection was obtained in CBF1 mice which received the skin
      graft of the SAG1 gene-vaccinated BALB/c mice.

PMID- 11228391
TI  - Plasmids encoding granulocyte-macrophage colony-stimulating factor and CD154
      enhance the immune response to genetic vaccines.
AB  - We examined whether plasmids encoding granulocyte-macrophage colony-stimulating
      factor (pGM-CSF) or CD40-ligand (pCD40L) could modify the immune response to
      antigen encoded by co-injected plasmid DNA. For this we used as antigen
      Escherichia coli beta galactosidase (beta-gal), encoded by the plasmid pLacZ. We
      found that intradermal co-injection of pLacZ with both pGM-CSF and pCD40L
      enhanced the anti-beta-gal IgG response by approximately two orders of magnitude
      compared to injections of pLacZ alone. Co-injection of both pGM-CSF and pCD40L
      with pLacZ significantly enhanced antigen-specific IgG, and in particular
      IgG(2a), over that of animals co-injected with pLacZ and either pGM-CSF or
      pCD40L. We found that co-injection of pGM-CSF and pCD40L with pLacZ enhanced the
      generation of beta-gal-specific cytotoxic T cells, and allowed for a significant
      expansion of CD8(+) T cells from splenocytes co-cultured with beta-gal expressing
      stimulator cells. The immunostimulatory effects induced by pGM-CSF or pCD40L
      required injection of these plasmids to the same site that received pLacZ.
      'Priming' experiments, where the site of injection was pre-injected with either
      plasmid adjuvant, showed that pGM-CSF, but not pCD40L, could enhance the anti
      beta-gal immune response induced by subsequently administered plasmid antigen. We
      conclude that plasmids encoding GM-CSF and CD154 are particularly effective
      genetic adjuvants when used together to enhance the humoral and cellular immune
      response to a plasmid-encoded antigen.

PMID- 11228392
TI  - Induction of virus-specific cytotoxic T lymphocytes by in vivo electric
      administration of peptides.
AB  - Generally, major histocompatibility complex (MHC) class I presentation of peptide
      antigens only occur for proteins' which are actively synthesized and processed
      intracellularly, so that immunization with a cytotoxic T lymphocyte (CTL) target
      peptide does not usually elicit effective CTL responses. In the present study, we
      explored the use of epitope peptides by in vivo electroporation to introduce
      directly into the cytoplasm for the vaccine elicitation of virus-specific CTLs in
      a mouse system. BALB/c mice were immunized with human immunodeficiency virus
      (HIV) env (P18, residues 311-320) or hepatitis C virus (HCV) NS5 (P17, residues
      2423-2434) with or without electric pulses. Effector cells against peptide
      labeled target cells were elicited in mice immunized with peptides with electric
      administration but not without electric administration. Moreover, cytolytic
      activities of CTL against peptide-labeled target cells were enhanced by the
      addition of plasmid having the immunostimulatory sequence (ISS) or cDNA of the B7
      1 molecule in electric administration of peptides. The results of the present
      study suggest that a peptide vaccine against a virus using electric
      administration is effective in eliciting virus specific CTLs.

PMID- 11228393
TI  - The development of the pathophysiological concept of calciphylaxis in experiment
      and clinic.
AB  - An attempt to clarify some pathophysiological aspects of calciphylaxis from both
      experimental and clinical points of view is presented. Until now, we cannot
      explain precisely various forms of calcification, affecting either soft tissues
      or biomaterial as well, only on the basis of metastatic or dystrophic
      calcification including the pure topical, local aspects. Therefore, the
      biological phenomenon of calciphylaxis can be useful in searching the ways for
      the inhibition of soft tissues and biomaterial calcification. The experiments
      with experimental progeria have also made it possible to study the so-called
      reversed calciphylaxis. The systemic reversed calciphylaxis, or
      'anacalciphylaxis' was shown in the authors experiments with the total artificial
      heart as a very effective factor in the inhibition of mineralization of the TAH
      driving diaphragms. The discovery of the ubiquitous organ regulator of
      calcification, osteopontin, can greatly contribute to further elucidation of the
      calciphylactic mechanisms in general, and also to the prevention of calcifying
      lesions. It is pointed to some clinical states, predominantly the end-stage renal
      disease with hemodialysation where many authors pay attention to calciphylaxis as
      a clinical entity in a series of such cases. Calciphylaxis has been described in
      dermatology, nephrology and other clinical disciplines. In the area of attempts
      to prevent the ectopic organ calcification and also mineralization of
      biomaterials, a vast field of stimulation of endogenic inhibitors of
      calcification remains open.

PMID- 11228394
TI  - Role of smooth muscle cell membrane potential in neointima formation in arteries
      of spontaneously hypertensive rats.
AB  - Based on observations that vascular smooth muscle cells (VSMC) from spontaneously
      hypertensive rats (SHR) have altered resting potentials as well as abnormal cell
      proliferation rates, neointima formation after controlled balloon injury was
      compared in arteries from SHR and Wistar Kyoto rats (WKY). SHR aortic VSMC showed
      hyperpolarized resting membrane potentials (-93+/-8 mV) when compared to those
      from WKY (-61+/-6 mV). Histomorphometric analysis of cross sections from aortic
      segments submitted to balloon injury showed reduced neointima formation in SHR
      (neointima/media ratio: 0.04+/-0.03) as compared to WKY (0.2+/-0.1). On the other
      hand, in injured carotid arteries, neointima formation was more extensive in SHR
      (neointima/media ratio 5.0+/-0.9) than in WKY (0.8+/-0.7), leading in most cases
      to luminal occlusion. Measurements of VSMC resting potential showed that carotid
      artery cells from SHR were depolarized with respect to those from WKY (-46+/-4
      vs. -69+/-5 mV, respectively). The results demonstrate an inverse relationship
      between VSMC membrane polarization and neointima formation in SHR arteries,
      suggesting that genetic modifications in SHR determine a dysfunctional cellular
      physiology that may influence cell proliferation subsequent to injury.

PMID- 11228395
TI  - Alterations in electrical and mechanical activity in Langendorff-perfused guinea
      pig hearts exposed to decreased external sodium concentration with or without
      hypotonic insult.
AB  - In order to examine electrical and mechanical effects of hyponatremia and
      hypotonicity, relevant to those in patients with 'water intoxication' syndrome,
      Langendorff-perfused guinea pig hearts were exposed to reduced NaCl
      concentrations (hypotonic [NaCl](0)-reduction) under the monitoring of left
      ventricular developed pressure (LVDP) and epicardial ECG. In some hearts,
      hyponatremia (from 140 to 80 mEq/l) was compensated for by adding mannitol to
      maintain osmolarity at a constant level (isotonic [NaCl](0)-reduction) or
      tetraethylammonium chloride to maintain both osmolarity and chloride
      concentrations at a constant level (isotonic [Na(+)](0)-reduction). Progressive
      isotonic [NaCl](0)-reduction increased LVDP, which was abolished in the presence
      of KB-R7943, a novel inhibitor of Na(+)/Ca(2+)-exchange. LVDP was reduced in
      hypotonic [NaCl](0)-reduction in which myocardial water content was increased. PQ
      interval and QRS duration were prolonged with both hypotonic and isotonic
      [NaCl](0)-reduction and these changes tended to be more pronounced with hypotonic
      than with isotonic [NaCl](0)-reduction. Similar ECG changes were also evident
      with isotonic [Na(+)](0)-reduction. Gd(3+) (1-5 uM), a blocker of stretch
      activated nonspecific cation channels, had no substantial effects on the
      electrical or mechanical changes seen with hypotonic [NaCl](0)-reduction. In
      conclusion, isotonic [NaCl](0)-reduction produced a positive inotropism by
      modulating Na(+)/Ca(2+)-exchange, whereas hypotonic [NaCl](0)-reduction led to
      negative inotropism, due in part to hypotonic myocardial swelling. In addition,
      [Na(+)](0)-reduction, irrespective of the concomitant [Cl(-)](0) or osmotic
      changes, depressed atrioventricular as well as intraventricular conduction.

PMID- 11228396
TI  - Acute immune response in respect to exercise-induced oxidative stress.
AB  - The relationship between exhaustive exercise, oxidative stress, the protective
      capacity of the antioxidant defense system and cellular immune response has been
      determined. Exhaustive exercise in well-trained young men (n=19)-induced
      leukocytosis, decreased proportion of activated-lymphocyte subsets (CD4+ and
      CD8+) expressing CD69, decreased lymphocyte mitogenic response to concanavalin A
      (ConA) and phytohemagglutinin (PHA), increased lipid peroxidation, increased
      total antioxidant status (TAS) and catalase activity, immediately after exercise.
      Suppressed blood concentration of T-lymphocyte subsets (CD3+, CD4+, CD8+, NK),
      increased TAS and blood total glutathione (TGSH) in early recovery period (30 min
      after exercise) were found. Strong positive correlation was observed between TGSH
      and lymphocyte mitogenic response to ConA and PHA (r=0.85 and 0.85, respectively)
      immediately after exercise. Moderate positive correlation was observed between
      TAS and lymphocyte mitogenic response to PHA (r=0.59) immediately after exercise
      as well as between TAS and lymphocyte mitogenic response to PHA and ConA (r=0.69
      and 0.54, respectively). Moderate to weak correlation was observed between TAS
      and conjugated dienes with exercise (r=0.66) as well as in 30-min recovery
      (r=0.50). After a short-term bout of exhaustive exercise, immune system was
      characterized by acute phase response, which was accompanied with oxidative
      stress. Suppression of the cellular immunity 30 min after exercise shows that
      this period is not enough for recovery after exhaustive exercise. The results
      suggest the interactions between exercise-induced oxidative stress and immune
      response.

PMID- 11228397
TI  - Does nitric oxide generation contribute to the mechanism of remote ischemic
      preconditioning?
AB  - The protective effect of local or remote ischemic preconditioning (IPC) on
      subsequent 40-min ischemic and 120-min reperfusion myocardial damage was
      investigated. Preconditioned rats underwent one cycle of myocardial
      ischemia/reperfusion consisting of 5-min ischemia produced as a left coronary
      artery (LCA) occlusion and 5 min of reperfusion. Remote IPC was produced as 15
      min of small intestinal ischemia with 15 min of reperfusion as well as 30 min of
      limb ischemia with 15 min of reperfusion. A marked protective action was afforded
      by both IPC protocols with a more significant effect of local (classic) ischemic
      preconditioning. Since the protective effect of remote IPC was not abolished by
      nitric oxide (NO) synthase inhibition with Nomega-nitro-L-arginine (L-NNA) it is
      concluded that NO generation may not be involved in the mechanism of remote IPC.

PMID- 11228399
TI  - Effects of magnetic fields on the accumulation of thiobarbituric acid reactive
      substances induced by iron salt and H(2)O(2) in mouse brain homogenates or
      phosphotidylcholine.
AB  - In this study, we examined the effects of magnetic fields (MFs) on the generation
      of thiobarbituric acid reactive substances (TBARS) in the mouse brain homogenates
      or phosphotidylcholine (PC) solution, incubated with FeCl(3) and/or H(2)O(2).
      Active oxygen species were generated and lipid peroxidation was induced in mouse
      brain homogenates by incubation with iron ions, resulting in the accumulation of
      TBARS. Lipid peroxidation was induced in PC by incubation with iron ions and
      H(2)O(2). Exposure to sinusoidal MFs (60 Hz, 0.2-1.2 mT), symmetric sawtooth
      waveform MFs (50 Hz, 25-600 mT/s), rectangular MFs (1/0.4-1/16 Hz, 3.3 mT) and
      static MFs (1, 5-300 mT) had no effect on the accumulation of TBARS in brain
      homogenates induced by FeCl(3). In contrast, when the homogenates were incubated
      with FeCl(3) in static MFs (2-4 mT), the accumulation of TBARS was decreased.
      However, this inhibitory effect disappeared when EDTA was added to the homogenate
      and incubated with H(2)O(2). The accumulation of TBARS in PC solution incubated
      with FeCl(3) and H(2)O(2) was also inhibited by the static MF. These results
      indicate that only static MFs had an inhibitory effect on iron-induced lipid
      peroxidation and the effectiveness of this magnetic field on iron ion-induced
      active oxygen species generation is restricted to a so called 'window' of field
      intensity of 2-4 mT.

PMID- 11228398
TI  - Increased plasma tetrahydrobiopterin in septic shock is a possible therapeutic
      target.
AB  - Hemoperfusion with a column of polymyxin B immobilized on fibers (PMX) has been
      used to adsorb endotoxin in-patients with septic shock. PMX hemoperfusion (PMX-H)
      increases blood pressure (BP) too rapidly for the effect to be attributable to
      endotoxin removal. Since inducible NO synthase (iNOS) is known to be involved in
      the profound hypotension, we hypothesized that a decrease of tetrahydrobiopterin
      (BH(4)), an essential cofactor of iNOS, might account for the rapid effect of PMX
      H on BP, if plasma BH(4) is increased concomitantly with NO in septic shock
      patients and if PMX can decrease BH(4). BH(4) was evaluated by measuring total
      biopterin, which can include derivatives of BH(4) by using high-performance
      liquid chromatography (HPLC). We confirmed that PMX fabric time dependently
      decreased total biopterin concentration in vitro. The plasma level of total
      biopterin in shock patients was indeed markedly elevated compared with that in
      volunteers (131.1+/-33.4 vs. 10.4+/-1.1 nM, n=5, P<0.01). Level of NO metabolites
      (NOx) were 173.9+/-104.7 versus 28.7+/-11.6 uM (P<0.01). In beagles, plasma total
      biopterin was 44.7+/-6.9 nM at baseline, reached 118+/-28.6 nM after
      lipopolysaccharide (LPS) injection, and fell to 70.2+/-15.8 nM after PMX-H.
      Plasma NOx concentration was increased from 15.2+/-4.2 to 41.0+/-7.5 uM by LPS
      treatment. BP was 130+/-11.3 mmHg at baseline, 82.2+/-8.3 mmHg at 14 h after LPS,
      and 115.2+/-16.0 mmHg after PMX-H. In rats, plasma total biopterin was 88.8+/-1.5
      nM at baseline, 383.7+/-144.2 nM after LPS and 177.0+/-14.2 nM after PMX-H.
      Plasma NOx was also increased after LPS (from 34.6+/-4.4 to 1445.6+/-376.0 nM).
      The marked increase in total biopterin concomitantly with NOx in septic shock
      patients and its reduction by PMX-H in animal models of septic shock are
      consistent with our hypothesis, and appear to justify further research on BH(4)
      removal as a potential therapeutic target.

PMID- 11228400
TI  - Interleukin-4 reversed the Interleukin-1-inhibited proteoglycan synthesis through
      the inhibition of NO release: a possible involvement of intracellular calcium
      ion.
AB  - Interleukin-1 (IL-1) causes cartilage degradation through nitric oxide (NO)
      synthesis. Although Interleukin-4 (IL-4) antagonizes the IL-1-mediated cartilage
      degradation, the precise mechanisms are not clear. We examined the effect of IL-4
      on NO synthesis in parallel with intracellular Ca levels ([Ca(2+)]i) and
      proteoglycan (PG) synthesis. IL-4-inhibited IL-1-enhanced NO release in a dose
      dependent manner. IL-1-enhanced [Ca(2+)]i in the chondrocytes, and IL-4
      attenuated this increase. IL-4 reversed IL-1-inhibited PG synthesis. Accordingly,
      IL-4 reversed the IL-1-inhibited PG synthesis through the inhibition of NO
      release. An increase in [Ca(2+)]i with IL-1 is possibly involved in this action.

PMID- 11228401
TI  - Paper alert. Immunology.
AB  - A selection of interesting papers that were published in the two months before
      our press date in major journals most likely to report significant results in
      immunology.

PMID- 11228402
TI  - Web alert. Tumour immunology. Lymphocyte development.

PMID- 11228404
TI  - Immunity against cancer: lessons learned from melanoma.
AB  - Most major advances in human cancer immunology and immunotherapy have come from
      studies in melanoma. We are beginning to understand the immune repertoire of T
      cells and antibodies that are active against melanoma, with recent glimpses of
      the CD4(+) T cell repertoire. The view of what the immune system can see is
      extending to mutations and parts of the genome that are normally invisible.

PMID- 11228405
TI  - In vivo tracking of tumor-specific T cells.
AB  - Novel immunologic assays now enable visualization of the antigen-specific
      response to an extent not previously possible. Assessment of not only the numeric
      frequency but also the functional properties of individual tumor-specific T cells
      in the endogenous and manipulated immune response has provided insights that will
      facilitate the development of immunotherapeutic strategies.

PMID- 11228406
TI  - Differential processing of class-I-restricted epitopes by the standard proteasome
      and the immunoproteasome.
AB  - Upon exposure to IFN-gamma, the standard proteasome is replaced by the
      immunoproteasome, which contains LMP2, LMP7 and MECL1, and is considered more
      efficient at producing antigenic peptides presented to CD8(+) T cells. This view
      has been challenged this year by reports showing that some epitopes, mainly of
      self origin, are not processed by the immunoproteasome and that mature dendritic
      cells constitutively express immunoproteasomes and therefore cannot efficiently
      present such epitopes.

PMID- 11228407
TI  - Recognition of tumor cells by the innate immune system.
AB  - There has been a rapid increase in our understanding of the cellular components
      of the innate immune system, the receptors used to distinguish changes in
      homeostasis, and how these components integrate into an anti-tumor effector
      response. Recently, significant progress has been made in the identification of
      ligands for receptors that activate NK cells, and the results have implications
      for the recognition of tumor cells.

PMID- 11228409
TI  - Pluripotent hematopoietic stem cell development during embryogenesis.
AB  - Significant progress has been made towards a better understanding of the
      establishment of hematopoiesis in the embryo. Hematopoietic precursors have been
      shown to arise independently in the yolk sac and in the intra-embryonic mesoderm.
      From the combined analysis of differentiation potentials, expression patterns and
      mutant phenotypes, a picture has emerged: definitive hematopoietic precursors are
      transiently generated in a specific environment close to the endothelium of the
      main arteries.

PMID- 11228410
TI  - Chemokines in lymphopoiesis and lymphoid organ development.
AB  - An important role has emerged for chemokines in regulating the distribution of
      progenitor cells during hematopoietic cell development. As well as recruiting
      cells, chemokines promote cell retention and cytokine expression. Furthermore,
      chemokines have been found to have an inductive function in secondary lymphoid
      organ development.

PMID- 11228411
TI  - Transcription factor regulation of B lineage commitment.
AB  - The past year has provided insight into the mechanisms by which multipotent
      progenitors commit to differentiation through the B lymphocyte lineage. Mice
      lacking the Pax5 gene develop pro-B lymphocytes but these cells are not uniquely
      committed to the B lineage as they can give rise to all hematopoietic cell types
      if cultured under appropriate conditions. Regulators of lymphocyte proliferation
      and survival have also been identified that may allow lymphocytes to respond to
      information provided by the external environment.

PMID- 11228412
TI  - How to make ends meet in V(D)J recombination.
AB  - In most vertebrate species analyzed so far, the diversity of soluble or membrane
      bound antigen-receptors expressed by B and T lymphocytes is generated by V(D)J
      recombination. During this process, the coding regions for the variable domains
      of antigen-receptors are created by the joining of subexons that are randomly
      selected from arrays of tandemly repeated V, D (sometimes) and J gene segments.
      This involves the site-specific cleavage of chromosomal DNA by the lymphocyte
      specific recombination-activating gene (RAG)-1/2 proteins, which appear to have
      originated from an ancient transposable element. The DNA double-strand breaks
      created by RAG proteins are subsequently processed and rejoined by components of
      the nonhomologous DNA end-joining pathway, which is conserved in all eukaryotic
      organisms - from unicellular yeast up to highly complex mammalian species.

PMID- 11228413
TI  - B1 cells: similarities and differences with other B cell subsets.
AB  - Since their discovery, B1 B cells' origins and developmental pathways have eluded
      characterization. In the past year, focus on B1 B cells has shifted dramatically
      from developmental to functional aspects of these cells. Most advances have been
      made in describing the physiological activities of B1 cells, including their
      migration, activation by antigen and role in both autoimmunity and malignancy.

PMID- 11228414
TI  - Selection events operating at various stages in B cell development.
AB  - B cells have to progress through various checkpoints during their process of
      development. The three transcription factors E2A, EBF (early B cell factor) and
      Pax5 play essential roles in B cell commitment checkpoints. The various forms of
      the BCR and their downstream signaling molecules, which are expressed at
      different stages of B cell development, act as critical checkpoint guards
      allowing (positive selection) or preventing (negative selection) developmental
      progression. The recent advances on the molecular mechanisms operating at these
      various checkpoints are here summarized and discussed.

PMID- 11228415
TI  - Towards an understanding of somatic hypermutation.
AB  - How germinal center (GC) B cells diversify their rearranged immunoglobulin genes
      by somatic hypermutation is unknown. However, the GC-specific activation-induced
      cytidine deaminase has been identified as a key factor controlling two central GC
      specific events: somatic hypermutation and class-switch recombination of
      immunoglobulin genes. This factor may function as a catalytic subunit of an RNA
      editing complex or, more directly, on DNA as a deoxy-cytidine deaminase in the
      hypermutation domain and class-switch region. Deamination of deoxy-cytidines on
      both strands may result in staggered DNA double-strand breaks (DSBs) that, in the
      hypermutation domain, become processed by member(s) of newly identified error
      prone DNA polymerases. Direct evidence for DSBs in hot-spots of hypermutating
      immunoglobulin genes has been provided, implicating DSBs as reaction
      intermediates of an error-prone DSB-repair pathway acting specifically in GC B
      cells. These recent findings are key to the identification of the hypermutation
      mechanism.

PMID- 11228416
TI  - T cell fate specification and alphabeta/gammadelta lineage commitment.
AB  - The development of T cells from pluripotent stem cells involves a coordinated
      series of lineage-commitment steps. Common lymphoid precursors in the fetal liver
      or adult bone marrow must first choose between a T, B or NK cell fate. Committed
      T cell precursors in the thymus then differentiate into cells committed to the
      alphabeta or gammadelta lineages. Recent advances have been made in our
      understanding of the mechanisms underlying T cell fate specification and
      alphabeta/gammadelta lineage divergence.

PMID- 11228417
TI  - Signal strength in thymic selection and lineage commitment.
AB  - During development, alphabeta T cells undergo positive or negative selection and
      CD4(+)/CD8(+) lineage commitment-events that have a major impact on the
      functionality of the T cell repertoire. The precise mechanisms of these
      differentiative steps remain elusive. Research this year has focused on
      quantitative models of signaling. For positive selection, the timing and extent
      of ERK activation may be important. For lineage commitment, the extent of Lck
      recruitment and activation may be the decisive factor. Next, the search is on for
      the genes that commit the cell to the fate determined by these quantitative
      differences in signals.

PMID- 11228418
TI  - Molecular determinants of TCR expression and selection.
AB  - The process of T cell development in the thymus is tightly regulated, being
      dependent on the integration of signals required for thymocyte maturation and
      survival. Rearrangements, expression and signaling of TCR genes play an
      indispensable role in this developmental program. Recent advances have provided
      insights into the molecular mechanisms that regulate TCR repertoire formation at
      the level of alphabeta versus gammadelta T cell fate and CD4(+) versus CD8(+)
      lineage determination.

PMID- 11228419
TI  - Stability and commitment in T helper cell development.
AB  - Specialized effector activities that are required to eliminate various pathogens
      involve cytokines produced by specialized CD4(+) T cells subsets, dogmatically
      termed Th1 and Th2 cells. Despite some oversimplifications, this paradigm is
      useful for organizing the complex pathways that control forward and backward
      movements along the road of T cell differentiation. Effective immune memory
      relies, in part, on the maintenance of the T helper phenotype. This review will
      address basic issues that relate to the maintenance or reversibility of Th1/Th2
      states within the CD4(+) T cell lineage.

PMID- 11228420
TI  - Generation and maintenance of memory T cells.
AB  - Typical immune responses lead to the prominent clonal expansion of antigen
      specific T cells followed by their differentiation into effector cells. Most
      effector cells die at the end of the immune response but some of the responding
      cells survive and form long-lived memory cells. The factors controlling the
      formation and survival of memory T cells are discussed. Recent evidence suggests
      that T memory cells arise from a subset of effector cells. The longevity of T
      memory cells may require continuous contact with cytokines, notably IL-15 for
      CD8(+) cells.

PMID- 11228421
TI  - Exercise induced muscle damage and recovery assessed by means of linear and non
      linear sEMG analysis and ultrasonography.
AB  - This study was aimed at investigating the time-course and recovery from eccentric
      (EC) exercise induced muscle damage by means of surface electromyography (sEMG),
      ultrasonography (US), and blood enzymes. Five subjects (EC Group) performed two
      bouts of 35 EC maximum contractions with the biceps brachii of their non dominant
      arm, five subjects were tested without performing EC (Control Group: CNT). The
      maximal isometric force (MVC) was measured. Force and sEMG signals were recorded
      during 80% MVC isometric contractions. In EC and CNT subjects US assessment on
      non-dominant biceps brachii was performed; creatin kinase (CK) and lactic
      dehydrogenasis (LDH) plasma levels were also assessed. Force, sEMG and CK-LDH
      measurements were performed before EC and after it periodically for 4 weeks. The
      sEMG was analysed in time and frequency domains; a non-linear analysis (Lyapunov
      1st exponent, L1) of sEMG was also performed. After EC, the MVC was reduced by
      40% on average with respect to the pre-EC values. A significant decrease in the
      initial frequency content, and in the MDF and L1 decay (13-42% less than the pre
      EC values, respectively) was also observed. The sEMG amplitude (Root Mean Square,
      RMS) was unchanged after EC. The US revealed an increase in muscle belly
      thickness and in local muscle blood flow after EC. A complete recovery of all the
      considered parameters was achieved in two weeks. In conclusion sEMG analysis was
      confirmed as an early indicator of muscle damage. Muscle recovery from damage is
      followed by both sEMG and US and this may have useful clinical implications. Non
      linear analysis (L1) was revealed to be sensitive to early sEMG modifications
      induced by EC as well as able to follow the post EC changes in the sEMG.

PMID- 11228422
TI  - Influence of contraction force and speed on muscle fiber conduction velocity
      during dynamic voluntary exercise.
AB  - Before using electromyographic (EMG) variables such as muscle fiber conduction
      velocity (MFCV) and the mean or median frequency (MDF) of an EMG power spectrum
      as indicators of muscular fatigue during dynamic exercises, it is necessary to
      determine the influence of a joint angle, contraction force and contraction speed
      on the EMG variables. If these factors affect the EMG variables, their influence
      must be removed or compensated for before discussing fatigue. The vastus
      lateralis of eight normal healthy male adults was studied. EMG signals during non
      fatiguing dynamic knee extension exercises were detected with a three-bar active
      surface electrode array. EMG variables were calculated from the detected signals
      and compared with the angle of the knee joint, the extension torque and the
      extension speed. The extension torque was set at four levels with 10% intervals
      between 40 and 70% of the maximum voluntary contraction. The extension speed was
      set at five levels with 60 degrees /s intervals between 0 and 240 degrees /s.
      Because the joint angle unsystematically affected the MFCV, EMG variables at a
      given joint angle were extracted for comparison. The influence of the extension
      torque and speed on the extracted EMG variables was clarified with an ANOVA and a
      regression analysis. The statistical analyses showed that MFCV increased with the
      extension torque but did not depend on the extension speed. In contrast, MDF was
      independent of the extension torque but was dependent on the extension speed. MDF
      thus showed a behavior different from that of MFCV. It became clear that if MFCV
      is used as an indicator of muscular fatigue during dynamic exercises, it is at
      least necessary to extract MFCV at a predetermined joint angle and then remove
      the influence of extension torque on MFCV.

PMID- 11228423
TI  - A three-dimensional, six-segment chain analysis of forceful overarm throwing.
AB  - A three-dimensional, six-segment model was applied to the pitching motion of
      three professional pitchers to analyze the kinematics and kinetics of the hips,
      upper trunk, humerus and forearm plus hand of both the upper limbs. Subjects were
      filmed at 250 frames per second. An inverse dynamics approach and angular
      momentum principle with respect to the proximal endpoint of a rigid segment were
      employed in the analysis. Results showed considerable similarities between
      subjects in the kinetic control of trunk rotation about the spine's longitudinal
      axis, but variability in the control of trunk lean both to the side and forward.
      The kinetics of the throwing shoulder and elbow joint were comparable between
      subjects, but the contribution of the non-throwing upper limb was minimal and
      variable. The upper trunk rotators played a key role in accelerating the ball to
      an early, low velocity near stride foot contact. After a brief pause they resumed
      acting strongly in a positive direction, though not enough to prevent trunk
      angular velocity slowing, as the musculature of the arm applied a load at the
      throwing shoulder. The interaction moment from the proximal segments assisted the
      forearm extensor in slowing flexion and producing rapid elbow extension near ball
      release. The temporal onset of muscular torques was not in a strictly successive
      proximal-to-distal sequence.

PMID- 11228424
TI  - Mechanomyography and electromyography force relationships during concentric,
      isometric and eccentric contractions.
AB  - The purpose of this study was to investigate systematically if complementary
      knowledge could be obtained from the recordings of electromyography (EMG) and
      mechanomyography (MMG) signals. EMG and MMG activities were recorded from the
      first dorsal interosseous muscle during slow concentric, isometric, and eccentric
      contraction at 0, 25, 50, 75 and 100% of the maximal voluntary contraction (MVC).
      The combination of the EMG and MMG recordings during voluntary concentric
      isometric-eccentric contraction showed significant different non-linear EMG/force
      and MMG/force relationships (P<0.001). The EMG root mean square (rms) values
      increased significantly from 0 to 50% MVC during concentric and isometric
      contraction and up to 75% MVC during eccentric contraction (P<0.05). The MMG rms
      values increased significantly from 0 to 50% MVC during concentric contraction
      (P<0.05). The non-linear relationships depended mainly on the type and the level
      of contraction together with the angular velocity. Furthermore, the type of
      contraction, the contraction level, and the angular velocity influenced the
      electromechanical efficiency evaluated as the MMG to EMG ratio (P<0.05). These
      results highlight that EMG and MMG provide complementary information about the
      electrical and mechanical activity of the muscle. Different activation strategies
      seem to be used during graded isometric and anisometric contraction.

PMID- 11228425
TI  - Training-related changes in the maximal rate of torque development and EMG
      activity.
AB  - This study monitored the effects of a short-term elbow flexor training program on
      surface electromyographic (SEMG) spike activity. The experimental paradigm
      consisted of three test sessions separated by 2-week intervals. At the beginning
      of each session, participants (N=13) performed five maximal effort isometric
      contractions of the elbow flexors to serve as baseline. After 5 min of rest, the
      participants then engaged in a 30-trial isometric fatigue protocol during which
      maximal elbow flexion torque was measured with a load-cell, and the maximal rate
      of change in the torque (dtau/dt(max)) was obtained from the differentiated
      torque-time curve. Bipolar electrodes were used to monitor the SEMG spike
      activity of the biceps brachii. Mean spike amplitude (MSA) and mean spike
      frequency (MSF) were calculated for the torque development and constant-torque
      phases of the isometric contraction, termed Segment 1 and Segment 2,
      respectively. Mean power frequency (MPF) was also calculated for Segment 2. The
      five baseline contractions of the second and third sessions were compared with
      those of the first session and analyzed for training-related changes. Training
      increased dtau/dt(max) but failed to change maximal elbow flexion torque or MSA.
      However, there was an increase in the MSF during the torque development phase of
      the contraction (Segment 1). Both MSA and MSF were greatest during the constant
      torque phase of the isometric contraction (Segment 2). There was a strong linear
      correlation (r=0.90, P<0.05) between MSF and MPF during (Segment 2). We
      hypothesize that the increase in dtau/dt(max) is due to enhanced motor-unit rate
      coding. The demonstrated correlation between MSF and MPF measures will allow
      investigators to use spike analysis to examine the frequency content of the SEMG
      signal under non-stationary conditions.

PMID- 11228426
TI  - Mean frequency and signal amplitude of the surface EMG of the quadriceps muscles
      increase with increasing torque--a study using the continuous wavelet transform.
AB  - The continuous wavelet transform (CWT), a time-frequency method, was used when
      calculating mean frequency of the power spectrum (MNF) and signal amplitude (RMS)
      of the surface EMG to investigate their relationships to force during a gradually
      increasing knee extension (ramp). Based upon the CWT, MNF was redefined to
      include time dependence on the EMG signal frequency contents, the short-time MNF
      (STMNF). Surface EMG was recorded from vastus lateralis, rectus femoris and
      vastus medialis in 21 clinically healthy subjects during a brief, gradually
      increasing contraction up to 100% of a maximum voluntary contraction (MVC), with
      a duration of approximately 10 s. The relationships between the EMG variables and
      force using linear regression were determined for each subject. For vastus
      lateralis, we also investigated if certain aspects of the muscle morphology
      (i.e., proportions and areas of different fibre types) influenced the EMG-force
      relationship. For the majority of subjects (17-18 out of 21 subjects) there were
      significant positive correlations between STMNF and force in the three muscles.
      No sex differences were found in intercepts or regression coefficients of STMNF.
      The muscle morphology had a significant influence on the STMNF-force intercept
      and the regression coefficient. Positive and highly significant linear
      correlations between RMS and force were found for all subjects and all three
      muscles.In conclusion, time frequency methods can be applied when investigating
      EMG during brief contractions associated with non-stationarity. In a great
      majority of the subjects, and in the three muscles, significant linear force
      dependencies were found for STMNF. Thus, when evaluating muscle fatigue, e.g., in
      ergonomic situations, it is important to consider the force level as one factor
      that can influence the results. Morphological variables (fibre proportions and
      fibre areas) influenced the STMNF-force relationship in vastus lateralis.

PMID- 11228427
TI  - EMG activities and plantar pressures during ski jumping take-off on three
      different sized hills.
AB  - Different profiles of ski jumping hills have been assumed to make the initiation
      of take-off difficult especially when moving from one hill to another.
      Neuromuscular adaptation of ski jumpers to the different jumping hills was
      examined by measuring muscle activation and plantar pressure of the primary take
      off muscles on three different sized hills. Two young ski jumpers volunteered as
      subjects and they performed several trials from each hill (K-35 m, K-65 m and K
      90 m) with the same electromyographic (EMG) electrode and insole pressure
      transducer set-up. The results showed that the differences in plantar pressure
      and EMGs between the jumping hills were smaller than expected for both jumpers.
      The small changes in EMG amplitudes between the hills support the assumption that
      the take-off was performed with the same intensity on different jumping hills and
      the timing of the gluteus EMG demonstrates well the similarity of the muscle
      activation on different hills. On the basis of the results obtained it seems that
      ski jumping training on small hills does not disturb the movement patterns for
      bigger hills and can also be helpful for special take-off training with low
      speed.

PMID- 11228429
TI  - Web alert. Genome studies and molecular genetics/plant biotechnology.

PMID- 11228431
TI  - Sequence and analysis of the Arabidopsis genome.
AB  - The comprehensive analysis of the genome sequence of the plant Arabidopsis
      thaliana has been completed recently. The genome sequence and associated analyses
      provide the foundations for rapid progress in many fields of plant research, such
      as the exploitation of genetic variation in Arabidopsis ecotypes, the assessment
      of the transcriptome and proteome, and the association of genome changes at the
      sequence level with evolutionary processes. Nevertheless, genome sequencing and
      analysis are only the first steps towards a new plant biology. Much remains to be
      done to refine the analysis of encoded genes, to define the functions of encoded
      proteins systematically, and to establish new generations of databases to capture
      and relate diverse data sets generated in widely distributed laboratories.

PMID- 11228432
TI  - Arabidopsis gene knockout: phenotypes wanted.
AB  - Gene knockout is considered to be a major component of the functional genomics
      toolbox, and is aimed at revealing the function of genes discovered through large
      scale sequencing programs. In the past few years, several Arabidopsis populations
      mutagenized with insertion elements, such as the T-DNA of Agrobacterium or
      transposons, have been produced. These large populations are routinely screened
      for insertions into specific genes, allowing mass-isolation of knockout lines.
      Although many Arabidopsis knockouts have already been obtained, few of them have
      been reported to present informative phenotypes that provide a direct clue to
      gene function. Although functional redundancy explains the lack of phenotypical
      alterations in some cases, it also appears that many mutations are conditional
      and/or do not alter plant morphology even in the presence of severe physiological
      defects. Consequently, gene knockout per se is not sufficient to assess gene
      function and must be integrated into a more global approach for determining
      biological functions.

PMID- 11228433
TI  - Contribution of the Tos17 retrotransposon to rice functional genomics.
AB  - The ongoing international efforts of the Rice Genomic Sequencing Project have
      already generated a large amount of sequence data. The next important challenge
      will be to construct saturation mutant lines for the functional analysis of all
      of the genes revealed by this effort in the context of the rice plant as a whole.
      Recently, the endogenous retrotransposon Tos17 has been shown to be an efficient
      insertional mutagen. Considering the ease of mutagenesis with Tos17 and its
      multiple-copy nature, saturation mutagenesis with this retrotransposon should be
      feasible in rice. Ongoing reverse-genetics studies, such as the PCR-screening of
      mutants and cataloguing of mutants by sequencing Tos17-insertion sites, as well
      as traditional forward-genetics studies, have clearly demonstrated that the Tos17
      system can significantly contribute to the functional genomics of rice.

PMID- 11228434
TI  - Gene silencing and DNA methylation processes.
AB  - Epigenetic gene silencing results from the inhibition of transcription or from
      posttranscriptional RNA degradation. DNA methylation is one of the most central
      and frequently discussed elements of gene silencing in both plants and mammals.
      Because DNA methylation has not been detected in yeast, Drosophila or
      Caenorhabditis elegans, the standard genetic workhorses, plants are important
      models for revealing the role of DNA methylation in the epigenetic regulation of
      genes in vivo.

PMID- 11228435
TI  - Genetic and molecular dissection of naturally occurring variation.
AB  - Recent progress in plant genome analysis has made it possible to examine the
      naturally occurring allelic variation underlying complex traits. Many studies
      have described the genetic mapping of quantitative trait loci for several kinds
      of complex phenotypic traits. Some researchers have taken up the challenge of
      performing the molecular cloning of genes at these loci, and examples of cloning
      have recently been reported. Naturally occurring allelic variation could be a new
      resource for the functional analysis of plant genes.

PMID- 11228436
TI  - Genome-wide expression analysis of plant cell cycle modulated genes.
AB  - Genome-wide expression analysis is rapidly becoming an essential tool for
      identifying and analysing genes involved in, or controlling, various biological
      processes ranging from development to responses to environmental cues. The
      control of cell division involves the temporal expression of different sets of
      genes, allowing the dividing cell to progress through the different phases of the
      cell cycle. A landmark study using DNA microarrays to follow the patterns of gene
      expression in synchronously dividing yeast cells has allowed the identification
      of several hundreds of genes that are involved in the cell cycle. Although DNA
      microarrays provide a convenient tool for genome-wide expression analysis, their
      use is limited to organisms for which the complete genome sequence or a large
      cDNA collection is available. For other organisms, including most plant species,
      DNA fragment analysis based methods, such as cDNA-AFLP, provide a more
      appropriate tool for genome-wide expression analysis. Furthermore, cDNA-AFLP
      exhibits properties that complement DNA microarrays and, hence, constitutes a
      useful tool for gene discovery.

PMID- 11228437
TI  - Gene targeting in Physcomitrella patens.
AB  - Gene-targeting efficiency in the land plant Physcomitrella patens (Bryophyta) can
      only be compared with that observed in Saccharomyces cerevisiae. Sequencing
      programs and microbiological molecular genetic approaches are now being developed
      to unravel the precise function of plant genes. Physcomitrella patens, as the new
      'green yeast', might well become a major tool for functional genomic studies of
      multicellular eukaryotes.

PMID- 11228439
TI  - Directed molecular evolution in plant improvement.
AB  - Directed molecular evolution is a powerful tool to evolve genes with commercial
      applications. Its most common application is to evolve enzymes with improved
      kinetics, altered substrate or product specificities, or improved function in
      different cellular environments. The technique is beginning to be applied to
      goals relevant to agriculture. Recent examples include the generation of novel
      carotenoids, enhanced herbicide detoxification, and the improvement of insect
      resistance genes.

PMID- 11228440
TI  - Protein expression in plastids.
AB  - The genome of the plastid has generated much interest as a target for plant
      transformation. The characteristics of plastid transgenes both reflect the
      prokaryotic origin of plastid organelles and provide a unique set of features
      that are currently lacking in genes introduced into the plant nucleus. Recent
      progress has been made in understanding plastid expression of recombinant
      proteins.

PMID- 11228441
TI  - Cytochrome P450s as genes for crop improvement.
AB  - In the past year, several cytochrome P450 genes have been identified that will be
      important for generating crop protectants and natural medicinal products. Among
      these are the 2-hydroxyisoflavone synthase (CYP93C) and the indole-3-acetaldoxime
      N-hydroxylase (CYP83B1) genes, which catalyze the formation of isoflavones and
      glucosinolates, respectively.

PMID- 11228442
TI  - Why is defining authorship so important?

PMID- 11228443
TI  - What is an author?

PMID- 11228444
TI  - Academic otolaryngology in the new millennium: Are we falling behind?
AB  - OBJECTIVE: To determine if differences in publication rates have evolved over the
      past 3 decades for academic otolaryngologists. METHODS: Three random samples with
      50 academic otolaryngologists each were studied. These otolaryngologists
      completed training in 1 of the 3 time periods (1970-74, 1980-84, 1990-94)
      studied. Articles published within the first 5 years after graduation were
      tabulated and statistically analyzed. RESULTS: Academic otolaryngologists
      graduating in the 1970s, 1980s, and 1990s averaged 8.7, 8.9, and 6.4 publications
      during their first 5 years of academic practice, respectively. The first 2
      cohorts averaged 5.4 and 5.7 publications in the 4 major otolaryngology journals,
      versus 3.3 for 1990s graduates. Basic science publications increased for 1990s
      graduates over those of the 1970s and 1980s graduates. The percentage of first
      author articles remained stable. Despite these trends, only the drop in case
      reports was statistically significant (P = 0.023, ANOVA). CONCLUSION: Trends may
      be developing that predict decreasing publication rates for newly trained
      otolaryngologists entering academic practice.

PMID- 11228445
TI  - Allergy testing and immunotherapy in an academic otolaryngology practice: a 20
      year review.
AB  - OBJECTIVE: Allergic disease plays a central role in the clinical practice of
      otolaryngology. The purpose of this study was to review the 20-year experience of
      an allergy clinic integrated within an otolaryngology practice at a major
      academic institution. STUDY DESIGN: We performed a retrospective database review
      of over 3300 otolaryngology patients referred for allergy skin testing between
      1979 and 1999. RESULTS: Approximately 80% of patients referred for allergy
      testing in our clinic had positive test results, of which 75.7% went on to
      undergo desensitization. The most common allergen was house dust, with allergies
      to mites, ragweed, and grass also prevalent. Among current allergy immunotherapy
      patients, 30.8% have undergone nasal septal, turbinate, and/or endoscopic sinus
      procedures in addition to allergy management. Nasal obstruction was the symptom
      most frequently persistent despite immunotherapy and the one most frequently
      reported to be improved by surgery. CONCLUSIONS: The otolaryngologist-head and
      neck surgeon is uniquely qualified to perform comprehensive medical and surgical
      management for patients with complex disease processes involving a component of
      allergy. We believe that an integrated approach to allergy within an
      otolaryngology practice optimizes the treatment of such patients.

PMID- 11228446
TI  - Outcomes of acid suppressive therapy in patients with posterior laryngitis.
AB  - OBJECTIVE: To evaluate the results of acid suppressive therapy (AST) in posterior
      laryngitis (PL) patients with and without documented pharyngeal acid reflux
      (PAR). METHODS: The charts of all patients with PL who received AST and who had
      undergone pharyngeal pH monitoring were reviewed. Results of AST in patients with
      PL with and without documented PAR were evaluated by laryngeal examination,
      symptom scores, and self-reported overall benefit. RESULTS: Thirty-nine patients
      with PL had received AST and undergone pharyngeal pH monitoring. Follow-up ranged
      from 2 to 27 months. Laryngeal findings were improved in patients with and
      without PAR. Pretreatment total symptom scores were significantly greater than
      that of posttreatment in patients with and without documented PAR. Overall
      benefit from AST was reported by the majority of PL patients with and without
      documented PAR. CONCLUSION: These findings support the use of AST to reduce or
      eliminate signs and symptoms in PL regardless of documentation of PAR.

PMID- 11228447
TI  - Adductor muscle activity abnormalities in abductor spasmodic dysphonia.
AB  - OBJECTIVE: To determine laryngeal muscle activation abnormalities associated with
      speech symptoms in abductor spasmodic dysphonia (ABSD). STUDY DESIGN: Bilateral
      laryngeal muscle recordings from the posterior cricoarytenoid, thyroarytenoid,
      and cricothyroid muscles were conducted in 12 ABSD patients. Patients' measures
      were compared during speech breaks and during speech without breaks and with 10
      normal controls. RESULTS: Significant group differences were found in the
      thyroarytenoid muscle; the patients had significantly greater activity on the
      right side both during speech breaks and nonbreaks in comparison with the
      controls. Cricothyroid muscle levels were also increased on the right in the
      patients. CONCLUSION: An asymmetry in adductor muscle tone between the 2 sides in
      ABSD may account for difficulties with maintaining phonation and voice onset
      after voiceless consonants. SIGNIFICANCE: These abnormalities may indicate why
      PCA BOTOX injections have not been as effective in ABSD as thyroarytenoid
      injections have been in adductor spasmodic dysphonia.

PMID- 11228448
TI  - A fine-cut technique for permanent laryngeal sectioning.
AB  - BACKGROUND: A new technique for permanent sectioning of the human spinal cord has
      provided superior images over those produced with traditional methods.
      Application of this technique for sections of the human larynx may yield cost
      effective, efficient, and accurate laryngeal anatomic dissections. STUDY DESIGN
      AND METHODS: This study was designed to evaluate this technique for dissections
      of the human larynx. Laryngeal sections from cadavers were submerged in a
      celloidin solution, a derivative of wallpaper plaster, and frozen to -15 degrees
      C. After preparation, axial and coronal cuts of 100 microm were made with a
      Macrocut Tome sectioning system. RESULTS: Sections were completed in
      approximately 30 hours. Digitized photographs of the laryngeal sections provide
      detailed images of precise anatomic relationships. CONCLUSION: Celloidin-based
      sectioning of the human larynx yields precise anatomic information beyond
      standard radiographic imagining and previous permanent laryngeal sectioning
      techniques in a cost-efficient and timely manner. Black and white fine-section
      photographs are provided.

PMID- 11228449
TI  - Primary radiation therapy for early glottic cancer.
AB  - OBJECTIVES/HYPOTHESIS: Early glottic squamous cell carcinoma can be effectively
      treated with either radiation or surgical intervention. We evaluated our
      experience treating early glottic cancer with primary radiation therapy and our
      vertical hemilaryngectomy (VHL) salvage experience. STUDY DESIGN/METHODS:
      Retrospectively, patient records between January 1986 and December 1994 were
      reviewed and 45 patients with early glottic squamous cell carcinoma who received
      full-course radiation therapy at the Cleveland Clinic Foundation were identified.
      RESULTS: Local control after radiation therapy was 80% overall, 87.5% for T1
      lesions, and 75% for T2 lesions. Four patients underwent VHL for salvage after
      local recurrence; 1 was successfully salvaged with VHL. Five patients underwent
      total laryngectomy salvage after radiation therapy; all were successful. Only 1
      of the 6 patients who were originally candidates for VHL before radiation therapy
      was successfully salvaged with the larynx preserved. CONCLUSIONS: Our local
      control rates using primary radiation therapy are consistent with prior published
      series, but voice sparing salvage is poor.

PMID- 11228450
TI  - Creating a stable tympanic membrane perforation using mitomycin C.
AB  - OBJECTIVE: To determine the ability of topically applied mitomycin C to create a
      stable tympanic membrane perforation. STUDY DESIGN AND SETTING: Twenty-four rats
      underwent subtotal removal of the tympanic membranes bilaterally. Forty ears
      received 0.2 mg/ml of mitomycin C. The remaining 8 received phosphate-buffered
      saline solution (control). Photographs taken every 3 to 5 days for 44 days were
      digitally scanned and computer analyzed to calculate the percentage of residual
      perforation. Application of solutions, photography, and data analysis were
      performed in a blinded fashion. RESULTS: The mitomycin C treated ears had delayed
      closure time and healing rate (from day 0 to 25) compared to the control group.
      All controls healed by day 14. By day 44, 92.5% of the mitomycin C treated ears
      healed. CONCLUSION: Mitomycin C prolongs the closure and healing rate of
      myringotomies in rat tympanic membranes. SIGNIFICANCE: Myringotomy with
      concurrent mitomycin C application may be useful for creating an animal model for
      chronic tympanic membrane perforation and should be tested in human beings as a
      method to maintain myringotomy patency for long-term ventilation.

PMID- 11228451
TI  - Submucosal radiosurgical uvulopalatoplasty for the treatment of snoring: Is the
      monitoring of tissue impedance and temperature necessary?
AB  - OBJECTIVE: To determine the safety and efficacy of submucosal radiofrequency
      uvulopalatoplasty. This procedure uses fixed, predetermined parameters of
      application without the concomitant monitoring of tissue impedance and
      temperature in the submucosal radiofrequency induced ablation and volumetric
      reduction of the soft palate as a treatment of chronic socially disruptive
      snoring. DESIGN: This nonrandomized prospective study used preoperative and
      postoperative questionnaires and visual analogue scales to evaluate snoring and
      postoperative pain. SETTING: Treatments were performed on an outpatient basis in
      a community-based clinic. PATIENTS: Nineteen patients sought treatment for
      chronic socially disruptive snoring, without complaints of excessive daytime
      somnolence, who met the predetermined criteria of a respiratory distress index of
      less than 20. INTERVENTION: Radiofrequency energy (3.8 MHZ) was applied to the
      submucosal tissues of the soft palate through a specially designed needle
      electrode with a predetermined wattage and treatment time. The number of
      treatments ranged from 1 to 6 (mean, 3.1). Resolution of snoring or diminution of
      snoring, to the point where it was no longer bothersome to the patients' bedmate,
      was considered the successful endpoint of the treatments. RESULTS: Sixteen
      patients were successfully treated and satisfied with the results. Three patients
      had only mild or moderate improvement in snoring despite multiple treatments.
      Postoperative pain was rated as mild (< or = 3 on the visual analogue scale) in
      86% of treatments. In 8 (14%) of 58 treatments, mucosal injury was inadvertently
      sustained, but all healed without complications. CONCLUSION: Submucosal
      radiofrequency uvulopalatoplasty, using the described technique, appears to be a
      safe, effective, and well-tolerated treatment for chronic socially disruptive
      snoring. These initial results indicate that the concomitant monitoring of tissue
      impedance and tissue temperature during radiofrequency ablation and volumetric
      reduction of the soft palate is not necessary and adds significantly to the cost
      of the procedure.

PMID- 11228452
TI  - Spontaneous tonsillar hemorrhage.

PMID- 11228453
TI  - Congenital cervical teratoma: airway management and complications.

PMID- 11228454
TI  - Adjustable length tracheostomy tube for the morbidly obese and thick neck
      patient: a prototype.

PMID- 11228455
TI  - Organ preservation by transoral laser microsurgery in piriform sinus carcinoma.
AB  - OBJECTIVE: To determine the effectiveness of organ-preserving CO2 laser
      microsurgery for the treatment of piriform sinus carcinoma. METHODS: A
      retrospective review of 129 previously untreated patients undergoing CO2 laser
      microsurgery for the treatment of squamous cell carcinomas of the piriform sinus
      from 1981 to December 1996 was undertaken. The intention was complete tumor
      removal by preserving functionally important structures of the larynx.
      Distribution of tumors (Union Internationale Contre le Cancer/American Joint
      Committee on Cancer, 1992) was 24 cases with pT1, 74 with pT2, 17 with pT3, and
      14 with pT4 disease. Node status was positive in 68% of patients. Seventy-five
      percent of patients had stage III or IV disease. Forty-two percent of the
      patients were treated solely with surgery, and 58% had surgery and postoperative
      radiotherapy. The median follow-up interval was 44 months. RESULTS: Eighty-seven
      percent of patients were controlled locally. Neck recurrences occurred in 14.0%
      of patients, metachronous distant metastases with locoregional control in 6.2%,
      and second primary tumors in 18.6%. Twenty percent of patients died of TNM
      related deaths. The 5-year overall Kaplan-Meier survival rate was 71% for stages
      I and II and 47% for stages III and IV disease; the 5-year recurrence-free
      survival rates were 95% and 69%, respectively. CONCLUSION: A comparatively low
      local recurrence rate, a high recurrence-free survival rate, and the avoidance of
      laryngectomy favor function-preserving surgery of piriform sinus carcinomas.

PMID- 11228456
TI  - Management of bilateral vocal fold paralysis: experience at the University of
      Athens.
AB  - The treatment of patients with vocal fold paralysis presents a challenge to the
      otolaryngologist-head and neck surgeon. Many techniques have been proposed to
      manage individuals with unilateral or bilateral vocal fold paralysis. We herein
      describe the experience of our department in dealing with bilateral vocal fold
      paralysis. At the University of Athens, patients presenting with symptomatic
      bilateral paralysis are treated with a posterior cordectomy by using the CO2 or
      KTP-532 laser. During the last 5 years, we have treated 20 patients (8 men and 12
      women) presenting with symptomatic bilateral vocal fold paralysis. For
      augmentation of the glottic airway, a modification of Kashima's cordotomy was
      used, completing a partial posterior cordectomy of one or both true and false
      vocal folds with the CO2 laser (15 patients) and the KTP-532 laser (5 patients).
      An elective tracheotomy was done before the cordotomy. Complications, such as
      infection, stridor, or dyspnea, were minimal. Although no objective voice
      analysis was performed, all patients were able to communicate without any
      phonation device and were satisfied with the result of the surgery. When compared
      with other techniques, the advantages offered by the posterior cordectomy
      included rapidity and simplicity in concept, reliability of outcome, short
      hospitalization, low risk of complications, and the possibility for revision when
      necessary (posterior cordectomy). From the successful postsurgical results of
      this study, it can be concluded that the posterior cordectomy is a reliable
      treatment option for the management of patients with bilateral vocal fold
      paralysis.

PMID- 11228457
TI  - Neck-dissection surgical specimens treated by lymph node revealing solution.
AB  - The detection of metastatic lymph nodes in cancer patients is essential for
      determining the cancer stage, and thus, the therapeutic modalities. However, very
      small lymph nodes can easily be missed during routine examination. We described a
      "Lymph Node Revealing Solution" (LNRS) that helps to detect tiny lymph nodes in
      neck dissection specimens. Twenty-one consecutive specimens of neck-dissection
      were investigated. The entire surgical specimen, fixed at first in formalin, was
      searched for lymph nodes by the traditional method. These were excised and sent
      for processing. The remaining tissue was immersed for 24 hours in LNRS. The lymph
      nodes stood out as white chalky nodules on the background of the yellow fat. They
      were then excised, and examined. A total of 227 lymph nodes were detected by the
      traditional method; 38 (17%) were positive for metastasis. Using the LNRS method,
      an additional 72 nodes were identified, among them 8 (11%) were positive for
      metastases and 2 cases were upstaged. LNRS is an inexpensive and easy method of
      detecting tiny lymph nodes; it enhances significantly the yield of normal and
      metastatic nodes of neck-dissection specimens and helps to establish a more
      accurate staging.

PMID- 11228458
TI  - Efficacy of evaluation of audiometric results after stapes surgery in
      otosclerosis. I. The effects of using different audiologic parameters and
      criteria on success rates.
AB  - The Committee on Hearing and Equilibrium of the American Academy of
      Otolaryngology-Head and Neck Surgery proposed guidelines to provide more
      uniformity in reporting hearing results after middle ear surgery. One of the
      proposals was to include the hearing thresholds at 0.5, 1, 2, and 3 kHz in a 4
      frequency pure-tone average (PTA) and to use post-operative bone-conduction (BC)
      levels rather than preoperative BC levels in describing postoperative air-bone
      gaps (ABGs). The hearing results of 451 stapes operations were evaluated to
      analyze to what extent the choice of different audiologic criteria affects
      success rates. It appeared that choice of PTA significantly affects postoperative
      gain in air-conduction thresholds and ABG levels. If one takes the improvements
      in speech-reception thresholds as the gold standard, the gain in air-conduction
      correlates best with a gain in speech-reception threshold if a higher frequency,
      such as 3 or 4 kHz, is included in a 4-frequency PTA. Also, choice of
      preoperative or postoperative BC in computing postoperative ABGs had a
      significant effect on the mean postoperative ABG levels, showing more favorable
      results with the use of preoperative BC thresholds.

PMID- 11228459
TI  - Efficacy of evaluation of audiometric results after stapes surgery in
      otosclerosis. II. A method for reporting results from individual cases.
AB  - To standardize the reporting of hearing results after middle ear surgery, the
      Committee on Hearing and Equilibrium of the American Academy of Otolaryngology
      Head and Neck Surgery proposed 2 levels of guidelines: level 1 for reporting
      summary data and level 2 for reporting raw data. The Committee encourages the
      reporting of raw data from each individual case. However, in studies in which the
      examined population is too large, this can yield difficulties. With respect to
      this point, we designed a method for a simple visual presentation of hearing
      results in an attempt to provide data from each individually operated ear in a
      patient group. In this method the relation between the preoperative and
      postoperative bone-conduction levels is evaluated to assess overclosure and
      iatrogenic cochlear damage, and the relation between postoperative gain in air
      conduction and the preoperative air-bone gap is evaluated as a measure of
      technical success rate. This results in 2 plots, which we called the Amsterdam
      Hearing Evaluation Plots. Audiometric data from 451 stapes operations were used
      to demonstrate the use of the Amsterdam Hearing Evaluation Plots.

PMID- 11228460
TI  - Laser-assisted uvulopalatoplasty: short-term and long-term results.
AB  - OBJECTIVE: Snoring causes many problems for both snorers and family members.
      Significant improvement has been reported in subjective measures of snoring after
      laser-assisted uvulopalatoplasty (LAUP). However, there were few studies of the
      long-term results of LAUP from a large number of patients. The purpose of this
      study was to compare the short-term versus long-term results in patients
      undergoing this procedure. METHODS: LAUP has been performed on 340 snorers. The
      majority of the patients were male with simple snoring by history and confirmed
      by polysomnographic study. Data on patients were compared from preoperative to
      the short-term (6 months) and long-term (more than 3 years) postoperative
      assessment points. Statistic analysis was performed to assess the significance of
      differences between groups. RESULTS: Significant improvement was observed in
      snoring scale at 6 months and long-term. The mean follow-up was 40.5 months with
      a range of 36 to 50 months. There were significant differences between short-term
      and long-term results (P < 0.05). The change in body mass index was significantly
      different in the patients with and without recurrence (1.9 vs 0.5 kg/m(2), P <
      0.01). Two hundred fifty-five (75%) patients had long-term clinical success, and
      34 (12%) patients with short-term success failed long-term. CONCLUSION: LAUP in
      the treatment of simple snoring results in long-term success. However, patients
      are at risk of recurrence if they gain weight.

PMID- 11228461
TI  - Identification of internal acoustic canal in the middle cranial fossa approach: a
      safe technique.
AB  - BACKGROUND: The middle cranial fossa approach (MCFA) is a very valuable
      functional approach in the armamentarium of the neuro-otologic surgeon.
      Identification of the internal acoustic canal (IAC) in MCFA is one of the most
      tedious steps. Many techniques have been described to locate the IAC safely when
      using the MCFA. OBJECTIVE: We sought to describe a safe technique for
      identification of the IAC and to demonstrate its feasibility in temporal bone
      dissections, as well as to discuss our clinical experience with this technique.
      METHODS: The surgical anatomy of the 20 temporal bones were evaluated and
      measured, especially by defining the medial and lateral ends of the IAC and
      relations to the nearby located structures. Measurements were obtained at 3
      levels: the width of the IAC at the level of the fundus, the width of the IAC at
      the level of the porus, and the safe distance around the IAC at the meatal level.
      The medial and lateral IAC end widths were compared with each other and with the
      safe area at the meatal level. RESULTS: The smallest, the largest, and the mean
      values were recorded. The mean width of the IAC at the level of the porus was
      found to be more than 3-fold that of the width of the IAC at the level of the
      Bill's bar, and the ratio between the width of the medial safe area around the
      IAC and the lateral end of the IAC was found to be more than 7-fold as wide.
      CONCLUSION: This technique offers direct quick exposure of the IAC, without
      handling the facial nerve and the inner ear structures. Forty-five cases of
      operations with the same technique showed excellent ease and safety of
      identifying the IAC medially in the MCFA.

PMID- 11228462
TI  - Effect of endoscopic sinus surgery on asthmatic patients with chronic
      rhinosinusitis.
AB  - There have been several reports on the effectiveness of endoscopic sinus surgery
      (ESS) in asthmatic patients with chronic rhinosinusitis. Whether ESS has a
      positive effect on the clinical course of asthma still remains controversial.
      There have been several subjective evaluations but few objective results. We
      performed a study to evaluate the effectiveness of ESS in 19 patients with asthma
      who underwent ESS for rhinosinusitis. The use of antiasthma medication and
      postoperative asthma symptoms was analyzed. Objective changes of pulmonary
      function tests were evaluated. There was a significant improvement in diurnal and
      nocturnal asthma symptoms. Improvements in asthma medication scores were also
      confirmed, and individual asthma symptoms (dyspnea, cough, wheezing, and sputum
      production) improved significantly. Despite a reduction in use of antiasthma
      medication after ESS, the parameters of the pulmonary function tests did not
      change. Both subjectively and objectively, it seems that ESS, when used to treat
      asthmatic patients with chronic rhinosinusitis, can play a significant role in
      the clinical improvement of asthma.

PMID- 11228463
TI  - Identification of the facial nerve in the translabyrinthine approach: an
      alternative technique.
AB  - An alternative technique for the identification of the facial nerve at the fundus
      of the internal auditory canal is described.

PMID- 11228464
TI  - Investigation of the ototoxic effects of interferon alpha2A on the mouse cochlea.
AB  - This prospective randomized study investigates the possible toxic effects of
      interferon (IFN) alpha2A on the mouse cochlea. Thirty-six albino Swiss mice that
      were randomly assigned to 3 groups underwent baseline auditory brain stem
      response testing bilaterally to objectively assess baseline hearing levels. The
      first group received a single dose of 50,000 units, and the second group received
      100,000 units of IFN-alpha2A intraperitoneally, whereas the third group was given
      no medication. Repeat auditory brain stem response testing revealed a significant
      rise in mean baseline peak equivalent sound pressure level thresholds in the
      groups that received IFN (P < 0.001). Histologically, the cochleae of mice that
      received IFN had a decreased number of fibroblasts in the spiral limbus, as well
      as prominent cytoplasmic vacuolation of these cells, compared with control
      animals. Loss of hair cells was not observed. It is possible that reversible
      biochemical and metabolic changes in the cochlea, rather than morphologic
      abnormalities, manifest IFN ototoxicity.

PMID- 11228465
TI  - Factors related to nerve injury and hypocalcemia in thyroid gland surgery.
AB  - To identify potential risk factors related to complications after thyroidectomy,
      a study was designed that included 675 patients. Recurrent laryngeal nerve (RLN)
      paralysis, hypocalcemia, serohematoma, wound infection, and postoperative
      hemorrhage were evaluated. The rate of paralysis of the RLN was calculated on
      nerves at risk for hypocalcemia (n = 890) in patients undergoing bilateral
      procedures or unilateral procedures if they had previously undergone a
      contralateral operation (n = 321). Multivariate analysis was used to identify the
      relationships between the variables included in the study. All statistical tests
      received the same level of significance of 0.05. Permanent hypocalcemia occurred
      in 2.2% of the patients, whereas unilateral paralysis of the RLN developed in
      0.9%. Mortality was 0.1% in this series. The RLN paralysis had a significant
      relationship with preoperative diagnosis of malignancy (P < 0.03). Likewise,
      hypocalcemia was related to sex and surgical procedure (P < 0.03). Serohematoma
      was linked with age (P < 0.001), and hemorrhage was associated with previous
      radiation of the neck (P < 0.03).

PMID- 11228466
TI  - Cervical ganglioneuroma: report of a case.

PMID- 11228467
TI  - Giant cell reparative granuloma of the hyoid bone.

PMID- 11228468
TI  - Extramedullary plasmacytoma of the nasal cavity.

PMID- 11228469
TI  - Rhinosporidiosis: differential diagnosis of a large nasal mass.

PMID- 11228470
TI  - The pharmacokinetics and efficacy of different estrogens are not equivalent.
AB  - In the next decade many women will turn to the medical community for advice on
      maintaining or improving health after menopause. Estrogen replacement therapy,
      with or without progestins, alleviates menopausal symptoms, prevents or manages
      osteoporosis, and reduces the increased cardiovascular disease risk that results
      from estrogen deficiency caused by ovarian decline. Although several estrogen
      replacement products are available, the pharmacokinetics and efficacy of these
      products may vary depending on either the estrogen formulation or the route of
      administration, or both. For example, oral estrogens, which elicit a marked
      hepatic response, induce greater beneficial effects on serum lipoproteins than
      transdermal estrogens, which circumvent first-pass liver metabolism. Oral
      conjugated estrogens and transdermal estradiol increase bone density and prevent
      bone loss. This article summarizes the studies comparing estrogen formulations
      and discusses the differential effects of various estrogen products that promote
      postmenopausal health.

PMID- 11228471
TI  - The controversy surrounding indomethacin for tocolysis.
AB  - Indomethacin is a prostaglandin synthetase inhibitor sometimes used for
      tocolysis. Several placebo-controlled trials and trials comparing indomethacin to
      other potential first-line tocolytic agents support its efficacy for delaying
      delivery for >48 hours. Recent observational studies, however, have raised
      concerns about the safety of indomethacin, implicating it with increased rates of
      intraventricular hemorrhage and necrotizing enterocolitis. Careful analysis of
      these observational studies suggests that these results should be viewed with
      caution, because of uncontrolled confounding by indication. A recent decision
      analysis supports the risk/benefit analysis of indomethacin in this setting.
      Still, the future of indomethacin in preterm labor should be guided by well
      designed prospective clinical trials. Such studies are underway.

PMID- 11228473
TI  - Defining the incidence of serious complications experienced by oocyte donors: a
      review of 1000 cases.
AB  - A review of 1000 aspirations of oocyte donors was performed. Only witnessed
      events necessitating hospitalization or emergent intervention were considered
      significant. Seven (0.7% incidence) cases were noted, including severe ovarian
      hyperstimulation syndrome (n = 3), adverse reaction to intravenous anesthesia (n
      = 2), intra-abdominal bleeding after aspiration (n = 1), and bladder atony with
      hematuria after aspiration (n = 1).

PMID- 11228472
TI  - A randomized prospective comparative study of general versus epidural anesthesia
      for transcervical hysteroscopic endometrial resection.
AB  - OBJECTIVE: This study was undertaken to compare general versus epidural
      anesthesia during hysteroscopic endometrial resection for dysfunctional uterine
      bleeding. STUDY DESIGN: In a prospective comparative study, 24 women with
      abnormal uterine bleeding that was unresponsive to conservative medical
      management were randomly assigned to undergo hysteroscopic endometrial resection
      with either general or epidural anesthesia. RESULTS: The durations of the
      endometrial resection procedure were similar for women who had general and
      epidural anesthesia (28.3 +/- 4.2 minutes vs 27.5 +/- 5.4 minutes, respectively).
      However, there was a statistically significantly lower absorption of distention
      fluid in women who underwent the procedure with general rather than epidural
      anesthesia (380.8 +/- 158.2 mL vs 648.3 +/- 157.1 mL, respectively; P < .0005).
      CONCLUSION: A significantly lower amount of glycine distention fluid was absorbed
      during endometrial resection in women who underwent the procedure with general
      rather than epidural anesthesia.

PMID- 11228475
TI  - Identification of a silent pituitary somatotropic adenoma based on a paradoxic
      response of growth hormone on a thyrotropin-releasing hormone or gonadotropin
      releasing hormone provocation test.
AB  - Preoperative endocrinologic identification and surgical removal of a silent
      somatotropic adenoma among patients with either amenorrhea or galactorrhea, or
      both, are beneficial for the restoration of menstruation and ovulation. Paradoxic
      rises of serum growth hormone in either a thyrotropin-releasing hormone or a
      gonadotropin-releasing hormone provocation test and high serum growth hormone
      levels were noted in the 3 patients with a silent somatotropic adenoma.

PMID- 11228474
TI  - Human immunodeficiency virus 1 expression in the female genital tract in
      association with cervical inflammation and ulceration.
AB  - OBJECTIVES: Determining the source of human immunodeficiency virus 1 in the
      female genital tract and identifying factors that influence the amount of virus
      shed are important in the understanding of heterosexual human immunodeficiency
      virus 1 transmission. STUDY DESIGN: Cervicovaginal human immunodeficiency virus 1
      ribonucleic acid shedding was quantified before and after treatment of cervical
      squamous intraepithelial lesions in 14 women. Genotypic analysis was performed on
      peptide HIV-1 env gp120 of the major human immunodeficiency virus 1 species in
      plasma and cervicovaginal lavage of selected samples. RESULTS: At 2 to 4 weeks
      after treatment, when cervices were inflamed and ulcerated, human
      immunodeficiency virus 1 ribonucleic acid in lavage samples increased 1.0 to 4.4
      log 10. Genotypic analysis showed significant differences between the predominant
      human immunodeficiency virus 1 species in paired plasma and lavage samples from 2
      of 4 women, suggesting that the increase in human immunodeficiency virus 1 was
      the result of local viral replication. CONCLUSIONS: Cervical inflammation and
      ulceration are associated with local human immunodeficiency virus 1 expression,
      which increases as much as 10,000-fold the amount of human immunodeficiency virus
      1 shed into genital secretions. This may explain why sexually transmitted
      diseases are important risk factors for human immunodeficiency virus
      transmission.

PMID- 11228476
TI  - Relationship of the metabolic syndrome and obesity to polycystic ovary syndrome:
      a controlled, population-based study.
AB  - OBJECTIVE: Although hyperinsulinemia seems to be an essential feature of
      polycystic ovary syndrome, the frequency of gynecologic disorders related to
      polycystic ovary syndrome at a population level in women with evident metabolic
      syndrome is not known. STUDY DESIGN: We conducted a cross-sectional, population
      based study. Participants (N = 204) were recruited from a random sample of women
      in 5 age groups (range, 35-54 years) living in a defined area. Metabolic syndrome
      was considered to be present if 3 of the following 8 criteria were fulfilled: (1)
      first-degree relative with type II diabetes, (2) body mass index > or = 30 kg/m2,
      (3) waist/hip ratio > or = 0.88, (4) blood pressure > or = 160/95 mm Hg or drug
      treatment for hypertension, (5) fasting serum triglyceride level > or = 1.70
      mmol/L, (6) high-density lipoprotein cholesterol value < 1.20 mmol/L, (7)
      abnormal glucose metabolism, and (8) fasting insulin value > or = 13.0 mU/L. The
      frequency of metabolic syndrome was 106 (19.5%) of 543 cases. The control group
      consisted of 62 overweight women without central obesity or metabolic syndrome
      and 53 healthy lean women (body mass index < 27 kg/m2. RESULTS: The group with
      metabolic syndrome differed from the other women according to most of the
      selection criteria and also had the highest free testosterone concentration.
      However, there were no differences between the groups regarding parity,
      infertility problems, or obstetric outcome. However, oligomenorrhea appeared to
      be more common in women with metabolic syndrome, especially in those with more
      severe symptoms (46.2%), than in obese (25.4%) and lean (15.1%) control subjects.
      Polycystic-like ovaries were detected by vaginal ultrasonography with similar
      frequency (13.1%, 15.3%, and 13.2% in women with metabolic syndrome, obese women,
      and lean women, respectively). CONCLUSIONS: Surprisingly few women with metabolic
      syndrome had symptoms suggestive of polycystic ovary syndrome, in comparison with
      obese and lean women. Our results suggest that at the population level polycystic
      ovary syndrome only accounts for a distinct subgroup of a much wider problem,
      metabolic syndrome.

PMID- 11228477
TI  - Vaginal mesh erosion after abdominal sacral colpopexy.
AB  - OBJECTIVE: Our goal was to compare the prevalence of vaginal mesh erosion between
      abdominal sacral colpopexy and various sacral colpoperineopexy procedures. STUDY
      DESIGN: We undertook a retrospective analysis of all sacral colpopexies and
      colpoperineopexies performed between March 1, 1992, and February 28, 1999. The
      patients were divided into the following 4 groups: abdominal sacral colpopexy,
      abdominal sacral colpoperineopexy, and 2 combined vaginal and abdominal
      colpoperineopexy groups, one with vaginal suture passage and the other with
      vaginal mesh placement. Survival analysis and Cox proportional hazards models
      were developed to examine erosion rates and time to erosion between groups.
      RESULTS: A total of 273 abdominal sacral vault suspensions were performed with
      the use of permanent synthetic mesh. There were 155 abdominal sacral colpopexies
      and 88 abdominal sacral colpoperineopexies. Among the 30 combined abdominal
      vaginal procedures, 25 had sutures attached to the perineal body and brought into
      the abdominal field and 5 had mesh placed vaginally and brought into the
      abdominal field. Overall, mesh erosion was observed in 5.5% (15/273). The
      prevalence of mesh erosion was 3.2% (5/155) in the abdominal sacral colpopexy
      group and 4.5% (5/88) in the abdominal sacral colpoperineopexy group (P not
      significant). The rates of erosion when sutures or mesh was placed vaginally were
      16% (4/25) and 40% (2/5), respectively, and were significantly increased in
      comparison with the rates for abdominal sacral colpopexy (hazard ratio, 5.4; 95%
      confidence interval, 1.6-18.0; P = .005; vs hazard ratio, 19.7; 95% confidence
      interval, 3.8-101.5; P < .001). These variables retained their significance after
      we controlled for other independent variables, including age, concomitant
      hysterectomy, concomitant posterior repair, and estrogen status. The median time
      to mesh erosion was 15.6 months for abdominal sacral colpopexy, 12.4 months for
      abdominal sacral colpoperineopexy, 9.0 months in the suture-only group (P <
      .005), and 4.1 months in the vaginal mesh group (P < .0001). CONCLUSIONS: The
      rate of mesh erosion is higher and the time to mesh erosion is shorter with
      combined vaginal-abdominal sacral colpoperineopexy with vaginal suture and
      vaginal mesh placement in comparison with abdominal sacral colpopexy.

PMID- 11228479
TI  - Postmenopausal changes in serum cytokine levels and hormone replacement therapy.
AB  - OBJECTIVE: Our purpose was to investigate the effect of hormone replacement
      therapy on the postmenopausal changes in serum cytokine levels. STUDY DESIGN:
      Fifteen cytokines were measured by an enzyme-linked immunosorbent assay in 97
      untreated and hormone replacement-treated women. Thirteen women were examined
      before and during hormone replacement therapy. RESULTS: Serum concentrations of
      macrophage colony-stimulating factor were significantly (P < .05) lower during
      the early postmenopausal period (< or = 10 years) than the values in premenopause
      and the elevated levels in the late postmenopausal period (< or = 30 years). A
      significant increase in tumor necrosis factor alpha and a decline in transforming
      growth factor beta1 were found in late postmenopausal women. Serum levels of
      macrophage colony-stimulating factor in women receiving hormone replacement
      therapy were significantly higher than those in untreated postmenopausal women.
      Furthermore, hormone replacement therapy induced a significant (P < .01) increase
      in serum levels of macrophage colony-stimulating factor, whereas serum levels of
      other cytokines were not affected. CONCLUSION: It is well documented that
      macrophage colony-stimulating factor lowers serum cholesterol concentrations and
      prevents atherosclerosis. Inducing the production of macrophage colony
      stimulating factor is a possible additional mechanism of hormone replacement
      therapy in mediating the antiatherogenic effect.

PMID- 11228478
TI  - Role of androgens in the growth of endometrial carcinoma: an in vivo animal
      model.
AB  - OBJECTIVE: We sought to create an animal model for the development of endometrial
      cancer in women with androgen excess. We examined the effects of estradiol and
      androgen, both alone and as precursors to estrogen biosynthesis on human
      endometrial cancers transplanted into a nude mouse model. STUDY DESIGN: We
      transplanted an estrogen-responsive, well-differentiated, established human
      endometrial carcinoma, EnCa-101, subcutaneously into athymic male nude mice. We
      established, first, that aromatase was expressed in this cell line, inducible by
      estrogen. We measured the growth of the tumor in the various groups weekly with
      Vernier calipers. We examined the effects of estradiol and androgens, both
      aromatizable and nonaromatizable, on tumor growth. RESULTS: Estrogen-supplemented
      tumors showed the greatest rate of growth and were significantly greater than the
      growth rate in castrate mice. Androgen-supplemented tumors showed a growth rate
      similar to that of tumors without significant hormonal exposure (castrate mice).
      Dihydrotestosterone had no effect on tumor growth in comparison with an agonadal
      state. CONCLUSIONS: Aromatizable and nonaromatizable androgens have little growth
      promoting effect on a well-differentiated endometrial carcinoma. Estradiol is the
      most potent growth stimulus in our model.

PMID- 11228480
TI  - Recurrence of dysplasia after loop electrosurgical excision procedures with long
      term follow-up.
AB  - OBJECTIVE: The aim of this study was to determine the rates of recurrent
      dysplasia with longer follow-up durations and to determine whether margin status
      and other variables were associated with recurrence. STUDY DESIGN: A
      retrospective chart review was performed for all women who underwent a loop
      electrosurgical excision procedure at Wilford Hall Medical Center, Lackland Air
      Force Base, Texas, between January 1993 and December 1994. Extracted information
      included age, parity, indication for the loop electrosurgical excision procedure,
      histologic classification of the loop electrosurgical excision procedure
      specimen, margin status, and whether a "deep" (endocervical) pass had been
      performed. Follow-up data included findings of repeated cytologic examination,
      colposcopy, and biopsy if performed. RESULTS: The mean duration of follow-up for
      all women was 24 months. Margins were positive in 28%, with 73% of these being
      endocervical. The overall recurrent dysplasia rate was 31%, with a mean time to
      recurrence of 11.9 months. Participants with any positive margins had a higher
      recurrence rate than did those with negative margins (47% vs 26%; P = .009). High
      grade lesions at the margin were more commonly associated with recurrence than
      were low-grade lesions relative to those with clear margins (high-grade lesion vs
      negative margins, 55% vs 26%; P = .003; low-grade lesion vs negative margins, 36%
      vs 26%; P = .34). Recurrence was not associated either with the performance of an
      endocervical pass or with the histologic diagnosis of the loop electrosurgical
      excision procedure specimen. CONCLUSION: With comprehensive long-term follow-up,
      positive margins on loop electrosurgical excision procedure specimens were shown
      to be a risk factor for recurrence of cervical dysplasia, particularly when high
      grade lesions were seen at the margin. Recurrence was also considerable among
      women with negative margins. Women should be counseled regarding this risk, and
      the importance of follow-up should be emphasized.

PMID- 11228481
TI  - The role of human papillomavirus deoxyribonucleic acid assay and repeated
      cervical cytologic examination in the detection of cervical intraepithelial
      neoplasia among human immunodeficiency virus-infected women. Cervical Disease
      Study Group of the American Foundation for AIDS Research Community Based Clinical
      Trials Network.
AB  - OBJECTIVES: We sought to measure the characteristics of a quantitative human
      papillomavirus deoxyribonucleic acid assay and repeated cervical cytologic
      examination in screening for cervical intraepithelial neoplasia among human
      immunodeficiency virus-infected women. STUDY DESIGN: Human immunodeficiency virus
      infected women with screening CD4+ lymphocyte counts of < or = 500 cells/mm3 (n =
      103) were examined by quantitative human papillomavirus deoxyribonucleic acid
      assay and serial cervical cytologic examination and by colposcopy with biopsy and
      endocervical curettage during the course of 1 year. RESULTS: Quantitative
      measures of total human papillomavirus deoxyribonucleic acid and high-risk human
      papillomavirus deoxyribonucleic acid were strongly associated with any cervical
      intraepithelial neoplasia (P = .005) and high-grade cervical intraepithelial
      neoplasia (P = .0006), but they improved the sensitivity and negative predictive
      value of baseline screening only slightly when combined with cervical cytologic
      examination. Incident cervical intraepithelial neoplasia occurred frequently
      (20%) during 1 year of follow-up and was more common among human papillomavirus
      infected women. Repeated cytologic examination identified 60% of women with new
      cervical intraepithelial neoplasia. CONCLUSION: Human immunodeficiency virus
      infected women with at least mild immunosuppression have a high incidence of
      cervical intraepithelial neoplasia, which warrants close follow-up. Those with
      high baseline human papillomavirus deoxyribonucleic acid levels may be at the
      highest risk for incident cervical intraepithelial neoplasia.

PMID- 11228482
TI  - Surgically induced endometriosis attenuates accrual of bone mineral density in
      growing rats.
AB  - OBJECTIVE: A possible association of endometriosis with decreased bone mineral
      density in women has been proposed. It has been reported that cortical and
      trabecular bone mass of the distal portion of the radius is decreased in patients
      with endometriosis. The objective of this study was to investigate the
      relationship between endometriosis and bone mineral density with the use of a rat
      model. STUDY DESIGN: Cycling female Sprague-Dawley rats (180 days old) were
      randomly assigned to 1 of 2 groups. The treatment group (n = 16) underwent
      surgical induction of endometriosis. Female rats (n = 17) with surgically
      transplanted abdominal muscle served as control animals. Dual-energy x-ray
      absorptiometry measurements were obtained before surgery and after 90 days with a
      Lunar DPX-MD+ (GE Lunar, GE Medical Systems, Milwaukee, Wis) bone densitometer,
      with software standardized for small animal research. RESULTS: Experimental
      animals had grossly visible endometriotic disease at necropsy (90 days). The mean
      net change in total bone mineral density from baseline to 90 days in the control
      group was +0.019 +/- 0.002 g/cm2, whereas the mean net change in total bone
      mineral density for the experimental group was +0.013 +/- 0.002 g/cm2. The
      experimental group gained less bone than the control group (P = .02). CONCLUSION:
      The age-appropriate increase in bone mineral density known to occur in this
      animal model is attenuated by surgically induced endometriosis. This finding
      supports the idea that endometriosis might be associated with decreased bone
      mineral density.

PMID- 11228483
TI  - Location of the ureters in relation to the uterine cervix by computed tomography.
AB  - OBJECTIVE: Our aim was to determine the distance of the ureter from the cervix
      and the influence of age and weight on this distance. STUDY DESIGN: The distance
      of the ureter from the uterine cervix was determined by evaluating the computed
      pelvic tomograms from 52 women. Age and body mass index were compared to this
      distance by means of regression analysis. RESULTS: At the most dorsal reflection
      of the ureter, the average distance from ureter to cervical margin was 2.3 +/-
      0.8 cm (range, 0.1-5.3 cm). There was no relationship to age, but there was a
      linear relationship between this distance and body mass index (R2 = 0.075; P =
      .049); thus the ureter was slightly more proximal to the cervical margin in
      heavier women. CONCLUSIONS: In women with apparently normal pelvic anatomy, the
      average distance between the ureter and cervix is >2 cm. The finding that this
      distance is <0.5 cm in 12% of the women studied may explain the relatively common
      occurrence of ureteral injury during hysterectomy. The relationship between body
      mass index and location is clinically insignificant.

PMID- 11228484
TI  - Proliferative effects of combination estrogen and progesterone replacement
      therapy on the normal postmenopausal mammary gland in a murine model.
AB  - OBJECTIVE: The aim of the study was to analyze the proliferative response of the
      normal mammary gland to combination hormone replacement therapy with estrogen and
      progesterone in a murine model of early versus late postmenopausal states. STUDY
      DESIGN: Ovariectomized mice were injected daily for up to 56 days with estrogen
      plus progesterone, starting at either 1 or 5 weeks after ovariectomy to simulate
      early and late menopausal periods, respectively. At various times after
      treatment, proliferation was analyzed by deoxyribonucleic acid
      histoautoradiography and whole-mount preparations. The induction of progesterone
      receptor by estrogen was also analyzed. To distinguish between estrogen- and
      progesterone-specific responses, we tested the effects of the antiprogesterone
      mifepristone (RU 486) and the antiestrogen ICI 182,780. RESULTS: The acute
      response to estrogen-progesterone therapy in the early postmenopausal period
      resulted in duct-end enlargement, ductal side branching, alveolar bud formation,
      and a 100-fold increase in epithelial cell proliferation. This was caused by the
      dominant effect of progesterone acting through the progesterone receptor. In the
      late postmenopausal period the acute response produced only duct-end enlargement;
      the 100-fold increase in epithelial cell proliferation resulted from the dominant
      effect of estrogen. After long-term treatment, both early and late postmenopausal
      glands exhibited similar morphologic features and a 9-fold higher steady-state
      proliferation rate than was found in control-treated groups. CONCLUSIONS:
      Starting combined estrogen and progesterone hormone replacement therapy in either
      early or late postmenopause produced a persistent, steady-state 9-fold increase
      in epithelial cell proliferation, which could be a contributing factor to
      increased breast cancer risk. The acute response in the late postmenopausal
      period mimics the hormonal response of the pubertal mammary gland, which in
      rodents is the stage most susceptible to carcinogen-induced mammary
      tumorigenesis. These observations raise questions about increased susceptibility
      of the late postmenopausal gland to carcinogenesis and a role for hormone
      replacement therapy in the promotion of tumorigenesis.

PMID- 11228485
TI  - Randomized control study of the effects of raloxifene on serum lipids and
      homocysteine in older women.
AB  - OBJECTIVE(S): Raloxifene, a selective estrogen receptor modulator, has beneficial
      estrogen agonist effects on bone and cardiovascular risk factors and estrogen
      antagonist effects on the breast and uterus. Limited clinical data have shown a
      sustained decrease in total cholesterol, low-density lipoprotein cholesterol, and
      homocysteine levels; an elevated homocysteine level is an independent risk factor
      for atherosclerosis. All of these studies were conducted in relatively young
      populations of women (mean age, 52-54 years). Raloxifene does not affect hot
      flushes, a major immediate symptom of menopause. This drug may therefore be
      useful in older women to prevent osteoporosis and cardiovascular disease. The aim
      of this clinical study was to evaluate the effects of raloxifene on plasma lipids
      and homocysteine in older women. STUDY DESIGN: The subjects were 45 healthy
      postmenopausal women, aged 60 to 70 years. The women were randomly assigned to
      therapy with raloxifene or placebo, 60 mg/d for 1 year. Twenty-six women received
      raloxifene and 19 received placebo. Checkups were performed every 3 months. At
      baseline and after 3, 6, 9, and 12 months of treatment we measured homocysteine,
      total serum cholesterol, triglycerides, and both high-density lipoprotein and low
      density lipoprotein cholesterol. RESULTS: An effect on lipids was evident by 3
      months with no significant additional modification at 12 months. Mean low-density
      lipoprotein cholesterol levels were lowered by 15% and total cholesterol was
      lowered by 8.5%. No reduction in high-density lipoprotein cholesterol or
      triglycerides was observed. After 3 months of therapy, homocysteine was
      significantly lower than at baseline (9.9 +/- 1.6 vs 11 +/- 2.1 micromol/L; P <
      .05). The greatest reduction with respect to baseline was reached after 6 months
      of therapy (-19.5% +/- 3%; P < .05). CONCLUSION(S): The results of our study show
      that raloxifene at a dose of 60 mg/d reduces serum concentrations of low-density
      lipoprotein cholesterol and total cholesterol in healthy older women. Our study
      shows that in older women raloxifene leads to a 19.5% +/- 3% reduction in fasting
      homocysteine levels. Raloxifene may have a favorable effect on the incidence of
      cardiovascular disease in older women.

PMID- 11228486
TI  - Markedly elevated levels of vascular endothelial growth factor, fibroblast growth
      factor, and interleukin 6 in Meigs syndrome.
AB  - Analysis of serum and peritoneal and pleural fluid from a patient with Meigs'
      syndrome revealed high levels of vascular endothelial growth factor, fibroblast
      growth factor, and interleukin 6. Serum levels declined after removal of the
      ovarian tumor, along with resolution of ascites and hydrothorax. These findings
      suggest the involvement of these vasoactive factors in ascites and pleural fluid
      formation in Meigs' syndrome.

PMID- 11228487
TI  - Abnormality of calcium channel inhibitor released from fetal membranes in preterm
      labor.
AB  - OBJECTIVE: This study was undertaken to test the hypothesis that an inhibitor of
      uterine contractions acting at the level of the dihydropyridine receptor of the
      uterine L -type uterine calcium channel is released in greater amounts from fetal
      membranes before term than at term. STUDY DESIGN: Endogenous calcium channel
      inhibitor activity was generated with standardized 25-cm2 surface area fetal
      membrane samples from the following 4 categories of women: preterm in labor,
      preterm not in labor, term in labor, and term not in labor. The amount of
      inhibitor in each membrane category was quantified by means of a competitive
      binding assay. Inhibition of uterine contractions induced by Bay K 8644 (an L 
      type calcium channel agonist) was used as another test of endogenous calcium
      channel inhibitor activity released from fetal membranes of all 4 groups of
      patients. RESULTS: Endogenous calcium channel inhibitor activity was most
      variable but present in the greatest amount in fetal membranes of women who were
      preterm not in labor followed by those in women at term not in labor and at term
      in labor. Fetal membranes from women in preterm labor had the least amount of
      measured endogenous calcium channel inhibitor activity. Consistent with the
      competitive binding assay, endogenous calcium channel inhibitor activity from
      fetal membranes from women who were preterm not in labor, at term not in labor,
      and at term in labor inhibited Bay K 8644-induced uterine contractions. Fetal
      membranes from women in preterm labor did not inhibit Bay K 8644-induced
      contractions. Endogenous calcium channel inhibitor activity was present in the
      chorion, the decidua, and the placenta, with little activity in the amnion.
      CONCLUSION: The down-regulation of endogenous calcium channel inhibitor activity
      with advancing gestation is consistent with a potential role for this inhibitor
      in maintaining uterine quiescence and in regulating the transition into labor.
      One possible cause of idiopathic preterm labor may be an abnormally low amount of
      endogenous calcium channel inhibitor activity in fetal membranes.

PMID- 11228488
TI  - A comparison of costs associated with screening for gestational diabetes with two
      tiered and one-tiered testing protocols.
AB  - OBJECTIVE: The Fourth International Workshop on Gestational Diabetes recently
      suggested that two techniques, a 2-tiered protocol and a 1-tiered protocol, to
      screen for gestational diabetes mellitus are acceptable alternatives. This study
      was undertaken to compare the direct costs and patient time expenditures
      associated with implementing both techniques. STUDY DESIGN: A MEDLINE search was
      undertaken to determine the prevalence of positive and negative screening
      results. Direct costs of testing were estimated by determining the range of
      supply costs from manufacturers' catalogs and the labor costs by estimating the
      time required to perform each procedure and multiplying by the appropriate range
      of wages; these costs were then multiplied by the appropriate range of the number
      of procedures required to implement both protocols, and the totals were summed.
      Patient time expended was estimated by assigning test times of 1, 2, and 3 hours
      for the 50-g screening glucose challenge test, the 75-g oral glucose tolerance
      test, and the 100-g oral glucose tolerance test, respectively. If additional
      visits were required, 2 travel-time units were assigned each time a patient
      underwent a procedure. These units were multiplied by the range of patients
      undergoing various tests to implement the alternative protocols. RESULTS: We
      identified low and high direct costs, test times, and travel units per patient
      screened by the 1- and 2-tiered testing protocols. Low and high direct costs were
      $3.46 and $7.88, respectively, for the 2-tiered protocol and $5.64 and $10.88,
      respectively, for the 1-tiered protocol (relative ratios, 1.63 for low direct
      costs in each protocol and 1.38 for high direct costs in each protocol). Low and
      high test times were 1.4 and 1.5 hours, respectively, for the 2-tiered protocol
      and 2.0 and 2.0 hours, respectively, for the 1-tiered protocol (relative ratios,
      1.47 for low test times in each protocol and 1.32 for high test times in each
      protocol). Low and high travel units for the 2-tiered protocol were 0.2 and 0.3,
      respectively, when the glucose challenge test was given at the prenatal visit,
      and 2.2 and 2.3, respectively, when the test was not given at that time. Low and
      high travel units for the 1-tiered protocol were 8.3 and 5.8, respectively, when
      the glucose challenge test was given at the prenatal visit, and 0.89 and 0.85,
      respectively, when the test was not given at that time. CONCLUSIONS: The 2-tiered
      protocol appears to be associated with lower direct implementation costs and less
      patient time expenditure than the 1-tiered scheme. The 1-tiered protocol is
      associated with slightly less travel time, but this is unlikely to offset the
      test time advantage of the 2-tiered protocol. Until further data regarding the
      relative clinical utility of the 2 protocols become available, these factors may
      be important for clinicians in deciding which screening format to follow.

PMID- 11228489
TI  - Intracervical fibrin sealants: a potential treatment for early preterm premature
      rupture of the membranes.
AB  - OBJECTIVE: We report our experience with a transvaginally applied intracervical
      fibrin sealant at <24 weeks' gestation. STUDY DESIGN: This is an observational
      study of a referred patient population, with preterm premature rupture of the
      membranes at <24 weeks' gestation. RESULTS: Twelve women consented to our
      protocol. The mean gestational age at preterm premature rupture of membranes was
      19 weeks 4 days (range, 13-23 weeks); the mean gestational age at treatment was
      20 weeks 5 days (range, 17-23 weeks). All women had a diminution in the amount of
      amniotic fluid leakage with an increase in amniotic fluid index. Among the 12
      pregnancies (13 fetuses), there were 7 surviving neonates. Two women had apparent
      "resealing" of the membranes. CONCLUSION: Fibrin sealants in midtrimester rupture
      of the membranes may lead to improved outcomes and now warrant formal evaluation.

PMID- 11228490
TI  - An Australian twin study of the genetic basis of preeclampsia and eclampsia.
AB  - OBJECTIVE: We investigated maternal versus fetal genetic causes of preeclampsia
      and eclampsia by assessing concordance between monozygotic and dizygotic female
      co-twins, between female partners of male monozygotic and dizygotic twin pairs,
      and between female twins and partners of their male co-twins in dizygotic
      opposite-sex pairs. STUDY DESIGN: Two large birth cohorts of volunteer Australian
      female twin pairs (N = 1504 pairs and N = 858 pairs) were screened and
      interviewed, and available medical and hospital records were obtained and
      reviewed where indicated, with diagnoses assigned according to predetermined
      criteria. RESULTS: With strict diagnostic criteria used for preeclampsia and
      eclampsia, no concordant female twin pairs were found. Collapsing diagnoses of
      definite, probable, or possible preeclampsia or eclampsia resulted in very low
      genetic recurrence risk estimates. CONCLUSION: Results from these two cohorts of
      female twin pairs do not support clear, solely maternal genetic influences on
      preeclampsia and eclampsia. Numbers of parous female partners of male twins were
      too low for conclusions to be drawn regarding paternal transmission.

PMID- 11228491
TI  - Coagulation activation markers do not correlate with the clinical risk of
      thrombosis in pregnant women.
AB  - OBJECTIVE: Because coagulation activation markers have been shown to indicate an
      increased risk of thrombosis, we tested whether thrombin-antithrombin III
      complexes and D-dimers correlated with the risk assessment in pregnant women on
      the basis of clinical data. STUDY DESIGN: We divided a group of 261 pregnant
      women (305 pregnancies) into low- and high-risk groups according to the personal
      and family histories of thrombosis and the presence of a hereditary or an
      acquired thrombophilia. Women with a thrombotic event in the current pregnancy
      formed a separate group. All pregnancies with or without heparin therapy were
      closely monitored with thrombin-antithrombin III and D-dimer values for the
      entire course of the pregnancy. Retrospectively, the data were then correlated
      with the different groups and subgroups. RESULTS: The course of the mean thrombin
      antithrombin III values of all 305 pregnancies was close to or slightly above the
      upper cutoff line, whereas the D-dimer values were well within the normal range.
      Independent of heparin, there was no difference in the course of the thrombin
      antithrombin III and D-dimer values between the low- and high-risk groups. Only
      women with ongoing thrombosis during pregnancy had significantly higher thrombin
      antithrombin III and D-dimer values with or without heparin therapy. Among those
      individuals with elevated thrombin-antithrombin III or D-dimer values, there were
      no specific, recognizable patients who had elevated markers more often than
      others. CONCLUSIONS: Thrombin-antithrombin III and D-dimer values do not
      correlate with a risk stratification assessed by clinical criteria. There are
      many women at low clinical risk who have elevated markers, and there are many
      women at very high clinical risk who have normal markers. Thus thromboprophylaxis
      would often be used inadequately if the indication were based on coagulation
      markers.

PMID- 11228492
TI  - Association between raised serum relaxin levels during the eighteenth gestational
      week and very preterm delivery.
AB  - OBJECTIVE: Our aim was to evaluate a possible association between serum relaxin
      levels in the 18th gestational week and preterm delivery. STUDY DESIGN: We
      conducted a nested case-control study that was based on serum samples obtained in
      the 18th week of gestation from 1545 unselected healthy primiparous women. Eleven
      case subjects were delivered very early (9 spontaneously, 2 by indicated cesarean
      delivery) and 42 moderately early (41 spontaneously, 1 by indicated cesarean
      delivery); 123 control subjects (121 having spontaneous labor, 2 undergoing
      indicated cesarean delivery) were randomly selected among the women with delivery
      at term. RESULTS: The serum relaxin concentration during the 18th gestational
      week was 63% higher among subjects with very preterm deliveries than among
      control subjects (P = .01, Mann-Whitney test). High relaxin levels during the
      18th gestational week were associated with an increased risk of very preterm
      delivery (odds ratio, 11.3; 95% confidence interval, 2.14-59.1) and spontaneous
      very preterm delivery (odds ratio, 5.5; 95% confidence interval, 1.3-23). There
      was a negative correlation for case subjects and control subjects between serum
      relaxin concentrations during the 18th gestational week and gestational age at
      delivery (P < .05). CONCLUSION: Serum relaxin may be an independent predictor
      when identification of women at risk of very preterm delivery is attempted in the
      18th gestational week.

PMID- 11228493
TI  - Mutations in the gene for methylenetetrahydrofolate reductase, homocysteine
      levels, and vitamin status in women with a history of preeclampsia.
AB  - OBJECTIVE: This study was undertaken to assess frequencies of the
      methylenetetrahydrofolate reductase gene mutations cytosine-to-thymine
      substitution at base 677 (C677T) and adenine-to-cytosine substitution at base
      1298 (A1298C) and their interactions with homocysteine and vitamin levels among
      Dutch women with preeclampsia. STUDY DESIGN: Mutations were studied in the
      following 5 groups: 47 consecutive women with preeclampsia, 49 women with
      preeclampsia and with hyperhomocysteinemia, 36 women with preeclampsia but
      without hyperhomocysteinemia, 127 women with familial preeclampsia (typed for
      C677T mutations only), and 120 control subjects. Plasma levels of homocysteine,
      folate, and vitamin B12 were measured. RESULTS: Although 10.6% of the consecutive
      women with preeclampsia had strictly defined hyperhomocysteinemia (values >97.5th
      percentile), neither mutation was found in excess relative to the control group.
      Women with preeclampsia who had mild hyperhomocysteinemia (values >75th
      percentile) had a significant excess of the TT genotype (homozygosity for C677T
      mutation) relative to the women with preeclampsia who did not have
      hyperhomocysteinemia (odds ratio, 8.2; 95% confidence interval, 1.8-39). They
      also had significantly lower vitamin levels. CONCLUSION: Hyperhomocysteinemia in
      women with preeclampsia was associated with mutations in the gene for
      methylenetetrahydrofolate reductase, but the high frequency of
      hyperhomocysteinemia itself cannot be explained by these mutations alone.

PMID- 11228494
TI  - Recreational exercise and occupational activity during pregnancy and birth
      weight: a case-control study.
AB  - OBJECTIVE: Our purpose was to investigate the impact of exercise and occupational
      activity on birth weight. STUDY DESIGN: This case-control study involved
      singleton infants at > or = 34 weeks' gestation without congenital anomalies.
      Case subjects had birth weights at <15th percentile for gestational age, and 2
      control subjects were selected per case subject. Data were collected by self
      completed questionnaire and analyzed by means of logistic regression. RESULTS:
      Relative to those who participated in structured exercise 3 or 4 times per week
      during the third trimester, the odds of lower birth weight were substantially
      increased for those who exercised > or = 5 times per week (adjusted odds ratio,
      4.61; 95% confidence interval, 1.73-12.32) and modestly increased for those at
      the other extreme, who engaged in structured exercise < or = 2 times per week
      (adjusted odds ratio, 2.64; 95% confidence interval, 1.29-5.39). Other factors of
      importance to birth weight were maternal height, prepregnancy body mass,
      pregnancy weight gain, smoking in the third trimester, and nulliparity.
      CONCLUSIONS: Structured exercise frequency during late pregnancy is a determinant
      of birth weight.

PMID- 11228495
TI  - Predicting outcomes of trials of labor in women attempting vaginal birth after
      cesarean delivery: a comparison of multivariate methods with neural networks.
AB  - OBJECTIVE: Our aim was to assess the utility and effectiveness of a neural
      network for predicting the likelihood of success of a trial of labor, relative to
      standard multivariate predictive models. STUDY DESIGN: We identified 100 failed
      trials of labor and 300 successful trials of labor in women with a prior cesarean
      delivery performed at our institution. Information was collected on >70 potential
      predictors of labor outcomes from the medical records, including demographic,
      historical, and past obstetric information, as well as information from the index
      pregnancy. Bivariate analyses comparing women in whom a trial of labor failed
      with those whose trial succeeded were performed. These initial analyses were used
      to select variables for inclusion into our muitivariate predictive model. From
      the same data we trained and tested a neural network, using a back-propagation
      algorithm. The test characteristics of the multivariate predictive model and the
      neural network were compared. RESULTS: From the bivariate analysis a history of
      substance abuse (adjusted odds ratio, 0.27; 95% confidence interval, 0.09-0.80),
      a successful prior vaginal birth after cesarean delivery (adjusted odds ratio,
      0.13; 95% confidence interval, 0.05-0.31), cervical dilatation at admission
      (adjusted odds ratio, 0.53; 95% confidence interval, 0.31-0.88), and the need for
      labor augmentation (adjusted odds ratio, 2.15; 95% confidence interval, 1.14
      4.06) were ultimately discovered to be important in predicting the likelihood of
      the success or failure of a trial of labor. With these variables in the
      predictive model the sensitivity of the derived rule for predicting failure was
      77%, the specificity was 65%, and the overall accuracy was 69%. We also built a
      network using the 4 variables that were included in the final multivariate model.
      We were unable to achieve the same degree of sensitivity and specificity that we
      observed with the regression-based predictive model (sensitivity and specificity,
      59% and 44%). CONCLUSION: In this study a standard multivariate model was better
      able to predict outcome in women ttempting a trial of labor.

PMID- 11228496
TI  - Elevation of both maternal and fetal extracellular circulating deoxyribonucleic
      acid concentrations in the plasma of pregnant women with preeclampsia.
AB  - OBJECTIVE: Elevated amounts of circulating fetal deoxyribonucleic acid in
      maternal plasma have recently been detected in pregnancies complicated by
      preeclampsia. We attempted to confirm this finding and simultaneously examined
      the quantity of maternal circulating deoxyribonucleic acid. STUDY DESIGN:
      Circulating deoxyribonucleic acid was measured by realtime quantitative
      polymerase chain reaction in plasma samples obtained from 44 women with
      preeclampsia and a matched cohort of 53 normotensive pregnant women. RESULTS: We
      confirmed that circulating fetal deoxyribonucleic acid levels were significantly
      elevated in pregnancies complicated by preeclampsia (3194.6 vs 332.8 copies/mL; P
      < .001). We also showed for the first time that circulating maternal
      deoxyribonucleic acid levels are also elevated (219,023.9 vs 20,235.8 copies/mL;
      P < .001). The increases in these deoxyribonucleic acid levels corresponded to
      the severity of the disorder, and values were correlated with each other in
      pregnancies complicated by preeclampsia (r = 0.556; P < .001) but not
      normotensive pregnancies (r = 0.046; P = .747). CONCLUSION: The releases of both
      free fetal and maternal deoxyribonucleic acid were found to be affected in
      preeclampsia.

PMID- 11228497
TI  - Inducible change in the behavior of resistance arteries from circulating factor
      in preeclampsia: an effect specific to myometrial vessels from pregnant women.
AB  - OBJECTIVE: It has previously been observed that a circulating factor or factors
      may be responsible for the changes in vessel behavior that are postulated to
      underlie the pathogenesis of preeclampsia. We wished to ascertain whether such
      changes in endothelial function are dependent on the vascular bed under
      investigation. STUDY DESIGN: Myometrial and infracolic omental vessels resistance
      vessels were obtained at cesarean delivery or hysterectomy. After incubation with
      either plasma from women with preeclampsia or plasma from normotensive pregnant
      women, myographic techniques were used to assess the endothelium-dependent
      relaxations of these vessels. RESULTS: Incubation of myometrial vessels from
      normotensive pregnant women with plasma from women with preeclampsia resulted in
      a significant reduction in endothelium-dependent relaxation, an effect that was
      independent of the parity of the patients from whom the vessels had been taken.
      Incubation of omental vessels from normotensive pregnant women and myometrial
      vessels from nonpregnant women with plasma from women with preeclampsia had no
      effect on the endothelium-dependent relaxation observed. CONCLUSIONS: This study
      demonstrates that the inducible changes in resistance vessel behavior are
      dependent on the tissue bed under investigation and on the pregnancy status of
      the patient.

PMID- 11228498
TI  - Association between colonization with group B streptococci during pregnancy and
      preterm delivery among Danish women.
AB  - OBJECTIVE: We studied the relationship between group B streptococcal colonization
      and preterm delivery. STUDY DESIGN: In this prospective study at a single
      hospital in Odense, Denmark, cervicovaginal cultures were obtained at < or = 24
      weeks' gestation from all the women, at delivery from women with preterm
      deliveries, and from a random sample of women delivering at term. RESULTS: In
      2846 singleton births, there was no significant association between group B
      streptococcal colonization at <or = 24 weeks' gestation and preterm birth. After
      adjustment for the risk factors for preterm delivery, more women with preterm
      delivery (12/84, 14%) were colonized at delivery with group B streptococci than
      women with term deliveries (22/300, 7%; adjusted odds ratio, 3.0; 95% confidence
      interval, 1.4-6.8). Group B streptococcal colonization at < or = 24 weeks'
      gestation and at delivery was significantly less likely to occur in the presence
      of normal vaginal flora. CONCLUSION: Group B streptococcal colonization at
      delivery, but not at < or = 24 weeks' gestation, was associated with preterm
      delivery.

PMID- 11228499
TI  - Case-control study of antenatal cocaine use and platelet levels.
AB  - OBJECTIVE: Our aim was to determine the prevalence of thrombocytopenia in
      pregnant patients who did and did not use cocaine. STUDY DESIGN: A 1:1 case
      control study of 326 patients attending an inner-city, neighborhood-based
      antenatal program between January 1992 and December 1998 is presented. Data
      concerning cocaine use (history and urine toxicology study) and platelet count,
      along with gestational age, were compared by nonparametric techniques (chi2 test,
      Fisher exact test, Wilcoxon rank sums, and receiver operating characteristic
      curve). RESULTS: The prevalence of thrombocytopenia during pregnancy was not
      different between cocaine-using patients (13/160; 8.1%) and nonusing patients
      (11/160; 6.9%; difference not significant). In patients who abused cocaine and
      for whom both positive and negative urine screening results were obtained
      concomitantly with platelet levels, no difference in platelet counts was evident.
      Overall, thrombocytopenia occurred more often in the third trimester than earlier
      in pregnancy for both control and cocaine-using pregnant women. CONCLUSION:
      Cocaine use among pregnant women was not associated with thrombocytopenia. A low
      platelet count was found more often later in pregnancy.

PMID- 11228501
TI  - Outcomes among term infants when two-hour postnatal pH is compared with pH at
      delivery.
AB  - OBJECTIVE: This study was undertaken to measure infant outcomes when pH at birth
      was compared with neonatal pH determined within 2 hours of age. STUDY DESIGN: We
      retrospectively studied term infants born between January 1, 1988, and August 31,
      1998, who had umbilical artery blood pH measured at birth and again from the
      radial artery or umbilical artery within 2 hours after birth. Statistical
      significance was determined with the chi2 test. Odds ratios and 95% confidence
      intervals were calculated by means of the Mantel-Haenszel method. RESULTS: Data
      from a total of 1691 infants were analyzed: 178 (11%) had acidemia at birth (pH
      of <7.20) that persisted through the first 2 hours after birth; 110 (6%) had
      development of acidemia after birth; and 594 (35%) were born with a cord pH of
      <7.20 that improved after delivery. The remaining 809 infants (48%) did not have
      acidemia either at birth or during the neonatal period, and these served as the
      reference group. Seizures during the first 24 hours after birth were more likely
      among those infants with persistent acidemia (odds ratio, 13.0; 95% confidence
      interval, 6.3-26.7). The odds ratio for seizures among infants in whom acidemia
      developed after birth was 5.7 (95% confidence interval, 2.2-14.5). Other than the
      reference group, the infants who were born with acidemia that was corrected by 2
      hours after birth had the lowest risk of seizures (odds ratio, 2.5; 95%
      confidence interval, 1.2-5.3). Significant differences in neonatal outcomes
      persisted after correction for anomalies. CONCLUSION: The direction of pH change
      from birth to the immediate neonatal period was significantly related to
      morbidity and mortality among term infants who were ill at birth or became ill
      shortly thereafter.

PMID- 11228500
TI  - Occupational fatigue and preterm premature rupture of membranes. National
      Institute of Child Health and Human Development Maternal-Fetal Medicine, Units
      Network.
AB  - OBJECTIVE: The aim of this study was to prospectively determine the relationship
      between occupational fatigue and spontaneous preterm delivery segregated into the
      etiologically distinct categories of spontaneous preterm labor, preterm premature
      rupture of membranes, and indicated preterm delivery. STUDY DESIGN: A total of
      2929 women with singleton pregnancies at 22 to 24 weeks' gestation were enrolled
      in a multicenter (10 sites) Preterm Prediction Study. Patients reported the
      number of hours worked per week and answered specific questions designed to
      determine the following 5 sources of occupational fatigue described by Mamelle et
      al: posture, work with industrial machines, physical exertion, mental stress, and
      environmental stress. Fatigue was quantified (0-5 index) according to the number
      of these sources positively reported. Simple and Mantel-Haenszel chi2 tests were
      used to test the univariate association and hypothesis of a linear trend between
      sources of occupational fatigue and spontaneous preterm delivery. Covariables
      were considered by multivariate logistic regression analysis. Women who did not
      work outside the home were considered separately from those who worked but did
      not report any sources of occupational fatigue. RESULTS: Each source of
      occupational fatigue was independently associated with a significantly increased
      risk of preterm premature rupture of membranes among nulliparous women but not
      among multiparous women. The risk of preterm premature rupture of membranes
      increased (P = .002) with an increasing number of sources of occupational fatigue
      not working outside the home, 2.1%; working but not reporting fatigue, 3.7%;
      working with 1 source of fatigue, 3.2%; working with 2 sources of fatigue, 5.2%;
      working with 3 sources of fatigue, 5.1%; and working with 4 or 5 sources of
      fatigue, 7.4%. There was also a significant relationship (P = .01) between
      preterm premature rupture of membranes and an increasing number of hours worked
      per week among nulliparous women. Neither spontaneous preterm labor nor indicated
      preterm delivery was significantly associated with occupational fatigue among
      either nulliparous or multiparous women. CONCLUSION: The occupational fatigue
      index of Mamelle et al discriminated a group of nulliparous women at increased
      risk for preterm premature rupture of membranes. The relationship between preterm
      premature rupture of membranes and occupational fatigue or hours worked may
      provide guidelines according to which nulliparous women and their employers can
      be advised.

PMID- 11228502
TI  - Perinatal mortality and neonatal morbidity rates among twin pairs at different
      gestational ages: optimal delivery timing at 37 to 38 weeks' gestation.
AB  - OBJECTIVE: The aim of this study was to determine the gestational age at delivery
      associated with the lowest rates of perinatal mortality, respiratory distress
      syndrome, and long hospital stays among twins, with pair rates used to account
      for both infants in each twin pregnancy. STUDY DESIGN: We conducted a population
      based retrospective study that analyzed linked birth certificates, fetal and
      infant death certificates, and hospital discharge data for 8150 twin pairs born
      in Washington State during 1987 through 1997. The chi2 or Fisher exact test was
      used to assess the statistical significance. RESULTS: The nadirs of perinatal
      mortality rate, respiratory distress syndrome incidence, and long hospital stay
      rate were seen at delivery dates of 39, 40, and 38 weeks' gestation,
      respectively. Restriction to pairs delivered vaginally without the induction of
      labor revealed that the perinatal mortality rate was lowest for delivery at 37
      weeks' gestation, the gestational age at which the highest numbers of such
      spontaneously timed pairs were born. CONCLUSION: Induction of labor should be
      routinely considered for twins at 37 to 38 weeks' gestation.

PMID- 11228503
TI  - The relationship between oligohydramnios and the onset of preterm labor in
      preterm premature rupture of membranes.
AB  - OBJECTIVE: The objective of this study was to determine whether a reduced
      amniotic fluid volume was associated with the onset of preterm parturition in
      patients with preterm premature rupture of membranes. STUDY DESIGN: An amniotic
      fluid index was determined before transabdominal amniocentesis in 129 patients
      with preterm premature rupture of membranes (gestational age < or = 35 weeks).
      Amniotic fluid was cultured for aerobic and anaerobic bacteria, as well as for
      mycoplasmas. Survival techniques were used for analysis. RESULTS: Amniotic fluid
      index was < or = 5 cm in 29% of patients (38/129). Patients with an amniotic
      fluid index of < or = 5 cm had a significantly higher rate of positive amniotic
      fluid culture than those with an amniotic fluid index of >5 cm (42% [16/38] vs
      18% [16/91]; P<.01). Spontaneous preterm delivery within 24 hours and 48 hours
      was more frequent among patients with an amniotic fluid index of < or = 5 cm than
      those with an amniotic fluid index of >5 cm (for 24 hours, 29% vs 12%; for 48
      hours, 42% vs 21%; P<.05 for each). The amniocentesis-to-delivery interval was
      significantly shorter in patients with an amniotic fluid index of < or = 5 cm
      than in patients with an amniotic fluid index of >5 cm (median, 38 hours; range,
      0.2-1310 hours; vs median, 100 hours; range 0.1-2917 hours; P<.01). Moreover, Cox
      proportional hazards model analysis indicated that an amniotic fluid index of <
      or = 5 cm was a significant predictor of the duration of the pregnancy after
      adjustment for gestational age and the results of amniotic fluid culture (odds
      ratio, 2.4; 95% confidence interval, 1.4-3.9; P<.001). CONCLUSION: Patients with
      preterm premature rupture of membranes and an amniotic fluid index of < or = 5 cm
      are at increased risk for a shorter interval to delivery.

PMID- 11228504
TI  - Maternal weight, pregnancy weight gain, and the risk of antepartum stillbirth.
AB  - OBJECTIVE: This study investigated whether the risk of antepartum stillbirth
      increases with body mass index during early pregnancy and also investigated the
      association between weight gain during pregnancy and the risk of antepartum
      stillbirth. STUDY DESIGN: This population-based case-control study included 649
      women with antepartum stillbirths and 690 control subjects among Swedish
      nulliparous women. RESULTS: Compared with lean mothers (body mass index < or =
      19.9 kg/m2), the odds ratios for risk of antepartum deaths were as follows:
      normal weight (body mass index, 20.0-24.9 kg/m2) odds ratio, 1.2 (95% confidence
      interval, 0.8-1.7); overweight (body mass index 25.0-29.9 kg/m2), odds ratio, 1.9
      (95% confidence interval, 1.2-2.9); and obese (body mass index > or = 30.0 kg/m2)
      odds ratio, 2.1 (95% confidence interval, 1.2-3.6). For term antepartum death
      corresponding risks were even higher, with odds ratios of 1.6 (95% confidence
      interval, 0.9-2.6) for normal weight, 2.7 (95% confidence interval, 1.5-5.0) for
      overweight, and 2.8 (95% confidence interval, 1.3-6.0) for obese women,
      respectively. Maternal weight gain during pregnancy was not associated with risk
      of antepartum stillbirth. CONCLUSION: Maternal overweight condition increased the
      risk of antepartum stillbirth, especially term antepartum stillbirth, whereas
      weight gain during pregnancy was not associated with risk.

PMID- 11228505
TI  - Effect of fetal hyperinsulinism on oral glucose tolerance test results in
      patients with gestational diabetes mellitus.
AB  - OBJECTIVE: This study was undertaken to evaluate the impact of the fetoplacental
      glucose steal phenomenon on the results of oral glucose tolerance testing in
      pregnancies complicated by gestational diabetes mellitus with fetal
      hyperinsulinism. STUDY DESIGN: This was an analysis of the cases of 34 patients
      with two consecutive abnormal oral glucose tolerance test results and amniotic
      fluid insulin measurement before institution of insulin therapy. Patients were
      divided into groups on the basis of normal versus elevated amniotic fluid insulin
      concentrations. RESULTS: Oral glucose tolerance tests were done at a mean (+/-SD)
      of 24.9 +/- 5.7 and 30.7 +/- 3.2 weeks' gestation, and amniotic fluid insulin
      measurements were done at 31.1 +/- 3.2 weeks' gestation. In 13 women with
      gestational diabetes mellitus with normal amniotic fluid insulin concentration,
      maternal postload blood glucose levels at 1 hour increased by 12 mg/dL (168 vs
      180 mg/dL; 9.3 vs 10.0 mmol/L; P = .0006) during the course of 6 weeks. In
      contrast, in 21 women with gestational diabetes mellitus with elevated amniotic
      fluid insulin levels (>7 microU/mL; >42 pmol/L), 1-hour postload blood glucose
      levels decreased by 22 mg/dL (201 vs 179 mg/dL; 11.2 vs 9.9 mmol/L; P = .002)
      during the same period. The higher the amniotic fluid insulin level, the larger
      the decrease (R = 0.504; P =.02). Although low amniotic fluid insulin levels were
      correlated significantly with 1-hour glucose levels of the first and second oral
      glucose tolerance tests, high insulin levels were no longer correlated with the
      second oral glucose tolerance test. CONCLUSION: Exaggerated fetal glucose
      siphoning may provide misleading oral glucose tolerance test results in
      pregnancies complicated by fetal hyperinsulinism by blunting maternal postload
      glucose peaks. Consequently, oral glucose tolerance test results in a pregnancy
      complicated by gestational diabetes mellitus with a fetus that already has
      hyperinsulinemia may erroneously be considered normal.

PMID- 11228506
TI  - Role of angiotensin II in altered baroreflex function of conscious rabbits during
      late pregnancy.
AB  - OBJECTIVE: Pregnancy alters baroreflex control of heart rate in conscious
      rabbits, but the mechanism for this action is unknown. This study tested the
      hypothesis that endogenous angiotensin II is the mediator. STUDY DESIGN: To test
      this hypothesis the baroreflex relationship between arterial pressure and heart
      rate in conscious rabbits was determined before and after administration of the
      angiotensin II AT1 receptor antagonist losartan (n = 7) before pregnancy and at
      the end of gestation. RESULTS: Pregnancy decreased mean arterial pressure,
      increased heart rate, and modified the reflex by shifting the mean arterial
      pressure-heart rate relationship to a lower pressure level, by increasing minimum
      heart rate, and by decreasing baroreflex gain (P < .05). Before pregnancy,
      losartan decreased baroreflex gain but had no other effect on reflex function. In
      contrast, during late gestation losartan further decreased mean arterial
      pressure, further decreased reflex gain, decreased maximum heart rate, and
      shifted the curve to a lower mean arterial pressure level (P < .05). CONCLUSION:
      These results suggest that in conscious rabbits during pregnancy endogenous
      angiotensin II contributes to hypotension-induced tachycardia but does not
      decrease reflex gain or elevate minimum heart rate.

PMID- 11228508
TI  - Life-table analysis of the risk of perinatal death at term and post term in
      singleton pregnancies.
AB  - OBJECTIVE: This study was undertaken to estimate the cumulative risk of perinatal
      death associated with delivery at each gestational week both at term and post
      term. STUDY DESIGN: The numbers of antepartum stillbirths, intrapartum
      stillbirths, neonatal deaths, and surviving neonates delivered at between 37 and
      43 weeks' gestation in Scotland, 1985-1996, were obtained from national databases
      (n = 700,878) after exclusion of multiple pregnancies and deaths caused by
      congenital abnormality. The numbers of deaths at each gestational week were
      related to appropriate denominators: antepartum stillbirths were related to
      ongoing pregnancies, intrapartum stillbirths were related to all births
      (excluding antepartum stillbirths), and neonatal deaths were related to live
      births. The cumulative probability of perinatal death associated with delivery at
      each gestational week was estimated by means of life-table analysis. RESULTS: The
      gestational week of delivery associated with the lowest cumulative risk of
      perinatal death was 38 weeks' gestation, whereas the perinatal mortality rate was
      lowest at 41 weeks' gestation. The risk of death increased more sharply among
      primigravid women after 38 weeks' gestation because of a greater risk of
      antepartum stillbirth. The relationships between risk of death and gestational
      age were similar for the periods 1985-1990 and 1991-1996. CONCLUSION: Delivery at
      38 weeks' gestation was associated with the lowest risk of perinatal death.

PMID- 11228507
TI  - The Preterm Prediction Study: association between cervical interleukin 6
      concentration and spontaneous preterm birth. National Institute of Child Health
      and Human Development Maternal-Fetal Medicine Units Network.
AB  - OBJECTIVE: The aim of this study was to determine the interrelationship between
      cervical concentration of interleukin 6 and detection of fetal fibronectin and
      other risk factors for spontaneous preterm birth. STUDY DESIGN: All patients with
      spontaneous preterm birth at <35 weeks' gestation (case patients; n = 125) and
      subjects matched for race, parity, and center delivered at > or = 37 weeks'
      gestation (n = 125; control subjects) were selected from women enrolled in the
      National Institute of Child Health and Human Development's Preterm Prediction
      Study. Interleukin 6 concentrations were determined by enzyme-linked
      immunosorbent assay in cervical swabs obtained at 22 weeks' to 24 weeks 6 days'
      gestation. Cutoffs to define an elevated interleukin 6 concentration included the
      90th and 95th percentiles for control subjects (>305 and >538 pg/mL,
      respectively). RESULTS: The mean (+/-SD) interleukin 6 concentration was
      significantly higher in case patients than in control subjects (212 +/- 339 vs
      111 +/- 186 pg/mL; P = .008). With either cutoff value elevated interleukin 6
      concentration was significantly associated with spontaneous preterm birth (90th
      percentile, 20% vs 9.6%; P = .02; 95th percentile, 12% vs 4.8%; P = .04).
      Cervical interleukin 6 levels were highest within 4 weeks of delivery, and the
      trend continued until term. Elevated interleukin 6 concentration was not
      significantly associated with bacterial vaginosis, maternal body mass index <19.8
      kg/m2, or a short cervix (< or = 25 mm), but it was significantly associated with
      a positive cervicovaginal fetal fibronectin test result (90th percentile, odds
      ratio, 5.5; 95% confidence interval, 2.6-11.9; 95th percentile, odds ratio, 5.3,
      95% confidence interval, 2.1-12.9). The mean interleukin 6 concentration among
      women with a positive fibronectin test result was 373 +/- 406 pg/mL; that among
      women with a negative fetal fibronectin test result was 130 +/- 239 pg/mL (P =
      .001). In a regression analysis that adjusted for risk factors significantly
      associated with spontaneous preterm birth in this population (positive fetal
      fibronectin test result, body mass index <19.8 kg/m2, vaginal bleeding in the
      first or second trimester, previous spontaneous preterm birth, and short cervix)
      elevated cervical interleukin 6 concentration was not independently associated
      with spontaneous preterm birth (odds ratio, 1.8; 95% confidence interval, 0.8
      4.3). CONCLUSIONS: At 24 weeks' gestation cervical interleukin 6 concentration in
      women who subsequently had a spontaneous preterm birth at <35 weeks' gestation
      was significantly elevated relative to those who were delivered at term. The
      association was particularly strong within 4 weeks of testing. A positive fetal
      fibronectin test result was strongly associated with elevated cervical
      interleukin 6 concentration, but bacterial vaginosis was not.

PMID- 11228510
TI  - Radiofrequency ablation of human fetal sacrococcygeal teratoma.
AB  - OBJECTIVE: Fetuses with solid, highly vascularized sacrococcygeal teratomas can
      die as a result of the vascular steal syndrome. This is the first report in which
      a percutaneous technique, radiofrequency ablation, was used to interrupt blood
      flow to a sacrococcygeal teratoma in 4 human fetuses. STUDY DESIGN: A
      radiofrequency ablation probe was percutaneously inserted into the fetal tumor
      under ultrasonographic guidance. In 2 fetuses a significant portion of the tumor
      mass was ablated, whereas in the other 2 fetuses only the major feeding vessels
      were targeted. RESULTS: Two infants were delivered at 28 and 31 weeks' gestation,
      respectively, and are doing well. In 2 other cases hemorrhage into the tumor led
      to an unfavorable fetal outcome. CONCLUSION: Ablation of a majority of the tumor
      tissue in sacrococcygeal teratoma is not necessary and proved fatal in two
      instances. Targeted ablation of the feeding tumor vessels diminishes blood flow
      sufficiently to reverse high-output fetal heart failure.

PMID- 11228509
TI  - Vasoactive mediator release by fetal endothelial cells in intrauterine growth
      restriction and preeclampsia.
AB  - OBJECTIVE: Preeclampsia and fetal growth restriction are associated with poor
      placental perfusion, which may be accompanied by a compensatory release of
      vasoactive substances in the fetoplacental circuit. This study examines the
      effects of preeclampsia and fetal growth restriction on nitric oxide and
      prostacyclin signaling pathways in fetal endothelial cells. STUDY DESIGN: Human
      umbilical vein endothelial cells from 30 control pregnancies, 18 pregnancies with
      preeclampsia, and 9 pregnancies with intrauterine growth restriction were
      cultured. Intracellular cyclic guanosine monophosphate accumulation and 6-keto
      prostaglandin F1alpha production were determined. RESULTS: Intracellular
      accumulation of cyclic guanosine monophosphate was significantly higher in the
      preeclampsia group and lower in the growth restriction group than in the control
      group (9.8, 1.8, and 3.9 pmol/microg protein for 5 minutes, respectively),
      whereas 6-keto-prostaglandin F1alpha production was not significantly different
      in the 3 groups. CONCLUSION: The data suggest that the fetoplacental vascular
      response to preeclampsia is to increase production of cyclic guanosine
      monophosphate, perhaps to maintain vessel dilatation and maximum flow through
      placental villi. In fetal growth restriction the umbilical vein endothelial cells
      do not or cannot respond to chronic hypoxia by increasing cyclic guanosine
      monophosphate, which may lead to fetoplacental vasoconstriction.

PMID- 11228511
TI  - Residency selection: should interviewers be given applicants' board scores?
AB  - OBJECTIVE: The aim of this study was to determine the influence of advance
      knowledge of board scores on interviewers' assessments of residency applicants.
      STUDY DESIGN: During a 2-year period we prospectively evaluated our residency
      selection process. In year 1 interviewers were provided with each candidate's
      entire application, whereas in year 2 the United States Medical Licensing
      Examination scores were not included. In each year interviewers were asked to
      provide numerical assessments of the applicants solely on the basis of their own
      impressions of the interviews. Analysis was performed only for evaluations by
      interviewers who participated during both study periods under review. Interview
      scores were compared with United States Medical Licensing Examination part I
      scores within each year by means of a scatter plot and correlation coefficients.
      RESULTS: Applicant demographic characteristics were similar during years 1 and 2.
      Interview scores did not differ between year 1 (4.2 +/- 0.1) and year 2 (4.3 +/-
      0.1; P > .05). During year 1 interview and board scores were significantly
      correlated (correlation coefficient, 0.64; slope of best-fit line, 13.9), whereas
      there was a negative correlation in year 2 (correlation coefficient, -0.06;
      slope, -1.3). CONCLUSION: When they are available to interviewers, markers of
      academic achievement such as United States Medical Licensing Examination scores
      may bias the interview evaluation. The interview process when conducted in this
      manner may simply be a validation process for candidates already judged on the
      basis of the application alone. Knowledge of United States Medical Licensing
      Examination scores by the interviewers may therefore negate the interview as an
      independent means of evaluating candidates.

PMID- 11228512
TI  - Cesarean delivery rate among women with severe hypertensive disease--possible
      reduction with epidural anesthesia?

PMID- 11228514
TI  - A problematic model to predict intrauterine forces during shoulder dystocia.

PMID- 11228517
TI  - Global approach to human immunodeficiency virus-infected pregnant women:
      experience at the Catholic University of the Sacred Heart, Rome, Italy.

PMID- 11228518
TI  - Preconceptional intake of folate and vitamin B12 in the prevention of neural tube
      defects and Down syndrome.

PMID- 11228519
TI  - Bowel stimulation after hysterectomy.

PMID- 11228521
TI  - Epidural analgesia.

PMID- 11228525
TI  - Third International Society of Cancer Gene Therapy Meeting.

PMID- 11228523
TI  - Ultrasonographic investigations of flow patterns in the perfused human placenta.

PMID- 11228526
TI  - ABSTRACTS OF ORAL PRESENTATIONS AND INVITED LECTURES.

PMID- 11228527
TI  - ABSTRACTS OF POSTER DISCUSSIONS.

PMID- 11228528
TI  - Towards the optimal vector for prostate cancer gene therapy; a caPCURE meeting
      report.

PMID- 11228529
TI  - A pilot study of systemic corticosteroid administration in conjunction with
      intrapleural adenoviral vector administration in patients with malignant pleural
      mesothelioma.
AB  - One of the primary limitations of adenoviral (Ad) -mediated gene therapy is the
      generation of anti-Ad inflammatory responses that can induce clinical toxicity
      and impair gene transfer efficacy. The effects of immunosuppression on these
      inflammatory responses, transgene expression, and toxicity have not yet been
      systematically examined in humans undergoing Ad-based gene therapy trials. We
      therefore conducted a pilot study investigating the use of systemic
      corticosteroids to mitigate antivector immune responses. In a previous phase I
      clinical trial, we demonstrated that Ad-mediated intrapleural delivery of the
      herpes simplex virus thymidine kinase gene (HSVtk) to patients with mesothelioma
      resulted in significant, but relatively superficial, HSVtk gene transfer and
      marked anti-Ad humoral and cellular immune responses. When a similar group of
      patients was treated with Ad.HSVtk and a brief course of corticosteroids,
      decreased clinical inflammatory responses were seen, but there was no
      demonstrable inhibition of anti -Ad antibody production or Ad-induced peripheral
      blood mononuclear cell activation. Corticosteroid administration also had no
      apparent effect on the presence of intratumoral gene transfer. Although limited
      by the small numbers of patients studied, our data suggest that systemic
      administration of steroids in the context of Ad-based gene delivery may limit
      acute clinical toxicity, but may not inhibit cellular and humoral responses to Ad
      vectors.

PMID- 11228530
TI  - Combined suicide and granulocyte-macrophage colony-stimulating factor gene
      therapy induces complete tumor regression and generates antitumor immunity.
AB  - The use of prodrug-activated ("suicide") gene therapy has been shown to be
      effective in inducing tumor regression when only a small proportion of tumor
      cells contains the suicide gene. These experiments were designed to test whether
      additional therapeutic benefit may be obtained by stimulating the immune
      response. Murine MC26 colon carcinoma cells, either untransduced or transduced
      with genes for herpes simplex virus-1 thymidine kinase (HSV1-TK) or human GM-CSF,
      were injected subcutaneously into syngeneic BALB/c mice in various combinations.
      Inoculation of equal numbers of untransduced and HSV1-TK-containing cells
      followed by ganciclovir (GCV) treatment resulted in almost complete tumor
      regression, but by 7 weeks, tumors had recurred in all mice. A similar initial
      regression was obtained using equal numbers of cells containing HSV1-TK and GM
      CSF genes, but >80% of these mice remained tumor-free after 3 months. Groups of
      tumor-free mice that had received GM-CSF-containing cells were left for different
      periods of time and rechallenged with unmodified MC26 cells on the opposite
      flank. Of the mice rechallenged 14, 28, and 108 days later, 100%, 88%, and 57%,
      respectively, showed complete resistance to unmodified tumor cells. In mice that
      showed tumor regrowth, tumor volume was much less than in control mice. Adoptive
      transfer of spleen cells from resistant mice to naive syngeneic mice resulted in
      partial resistance to challenge with unmodified tumor cells. Specific
      cytotoxicity against MC26 cells was only demonstrable in mice receiving GM-CSF-
      and HSV1-TK-containing tumor cells. These experiments show that the presence of
      cells secreting GM-CSF in HSV1-TK-containing, regressing tumor is able to induce
      complete or partial resistance to tumor rechallenge. This indicates the potential
      usefulness of GM-CSF in enhancing other antitumor therapies.

PMID- 11228531
TI  - Experimental targeted radioiodide therapy following transfection of the sodium
      iodide symporter gene: effect on clonogenicity in both two-and three-dimensional
      models.
AB  - To evaluate the potential of the expression of the sodium/iodide symporter (NIS)
      as a means of targeting radioiodine to tumor cells, we have employed plasmid
      mediated transfection of the NIS gene into a range of mammalian cell hosts. We
      observed perchlorate-inhibitable iodide uptake up to 41-fold over control in all
      NIS-transfected cells. We assessed the effect of NIS expression followed by
      exposure to 131I- on the clonogenic survival of UVW glioma cells. After exposure
      of two-dimensional monolayer cultures of UVW-NIS cells to 131I- at a radioactive
      concentration of 4 MBq/mL, clonogenic survival was reduced to 21%. Similar
      treatment of UVW-NIS cells in three-dimensional spheroid cultures resulted in a
      reduction of clonogenic survival to 2.5%. This increase in sensitivity to 131I-
      exposure is likely to be due to a radiological bystander effect. These results
      are very encouraging for the development of a novel cytotoxic gene-therapy
      strategy in which a radiological bystander effect plays a significant role in
      tumor cell sterilization.

PMID- 11228532
TI  - The application of an anti-angiogenic gene (thrombospondin-1) in the treatment of
      human prostate cancer xenografts.
AB  - Angiogenesis is a critical event for solid tumor growth and metastasis. Within a
      given microenvironment, the angiogenic response is determined in part by the
      balance between angiogenesis inducers and inhibitors. The aim of this study was
      to establish a thrombospondin-1 (TSP-1) ( an antiangiogenic gene) expression
      vector, and to determine the feasibility for use of TSP-1 in prostate cancer gene
      therapy. The results of this study showed that pCR-TSP-1, the cloned TSP-1
      expression plasmid vector, expressed the TSP-1 gene efficiently in DU145, a human
      prostate cancer cell line. pCR -TSP-1 did not exert any significant growth
      inhibitory activity on the tested cell line in vitro. However, TSP-1
      overexpression inhibited the growth of DU-145 xenografts in Balb/c nude mice when
      directly transfected with pCR-TSP-1 in combination with a liposomal agent
      (DOSPER). Histological analysis showed that there were extensive areas of
      necrosis in the TSP-1 overexpressing tumors, whereas no necrotic foci were
      observed in the control tumors. Furthermore, the microvessel density was lower in
      the TSP-1 overexpressing tumors compared to the control tumors. These results
      suggest that TSP-1 may be a potentially useful gene for prostate cancer gene
      therapy.

PMID- 11228533
TI  - The expression of CD70 and CD80 by gene-modified tumor cells induces an antitumor
      response depending on the MHC status.
AB  - The expression of costimulatory molecules such as CD70 or CD80 by gene-modified
      tumor cells has been shown to enhance the antitumor immune response based mainly
      on T lymphocytes. However, most human tumors show defects of major
      histocompatibility complex (MHC) expression, preventing them from being
      recognized by MHC-restricted T cells. To investigate if coexpression of CD70 and
      CD80 costimulatory molecules induces comparable antitumor responses in low and
      high MHC-expressing tumor cells, we used two low immunogenic murine tumor models,
      the B16.F10 melanoma and the TS/A mammary adenocarcinoma cell lines expressing,
      respectively, low and high levels of MHC class I molecules. Transfection of both
      CD70 and CD80 genes resulted in an increased capacity of gene-modified tumor
      cells to costimulate in vitro the proliferation and cytokine production of
      optimally activated lymphoid cells. Coexpression of CD70 and CD80 by the two
      tumor cell lines, TS/A and B16.F10, resulted in both cases in partial regression
      of subcutaneous tumors. Immunochemical analysis and studies in nude mice showed
      that, even in the B16.F10 model, T cells had a significant role in the antitumor
      response induced by combining CD70 and CD80. However, rejection of the CD70/CD80
      transfected tumor cells appeared more effective in the MHC class I high TS/A
      model, leading to a protection against parental tumor cells. B16.F10 and TS/A
      transfectants were then tested with fibroblasts genetically modified to secrete
      interleukin-12 (IL-12) as a therapeutic vaccine in mice bearing parental tumors.
      In the two models tested, the injections of irradiated IL-12 and CD70/CD80 gene
      modified cells generated an antitumor response to established tumors leading to
      the slowing down of the tumor growth rate. Although the mechanisms remain to be
      defined, these findings suggest that the combination of several immuno-modulatory
      molecules could provide additional strategies for cancer immuno-gene therapy,
      even for MHC expression-deficient tumors.

PMID- 11228534
TI  - Induction of long-lasting cytokine effect by injection of IL-12 encoding plasmid
      DNA.
AB  - We have recently demonstrated that DNA coding for both subunits of the murine IL
      12 heterodimer exhibits a strong antimetastatic effect against B16-melanoma in
      C57BL/6 mice and after intratumoral injection tumor regression. Here we show that
      the antimetastatic effect can be detected when the DNA is injected
      intramuscularly 30 days before tumor cell challenge. A long-term IL-12 expression
      was measured for up to 50 days in the serum with a peak at day 20 amounting to
      about 10 ng/mL in C57BL/6 mice. CpG oligodeoxynucleotides also induce IL-12
      expression, however, only for a few hours. IL-12 DNA administration induces long
      lasting systemic IFN -gamma production, whereas IL-4 and TNF-alpha levels
      remained undetectable. NK cell-depleted mice showed a strong but reduced
      expression of murine IL-12. Expression of DNA encoding human instead of murine IL
      12 resulted in a significantly lower and transient expression, indicating that
      not plasmid-derived IL-12 production alone but the immune system of the host
      contributes to the long- lasting antimetastatic effect. It may be attributable to
      an autocrine feedback mechanism maintaining murine IL- 12 expression, whereby
      several cell populations including NK cells are involved.

PMID- 11228535
TI  - Heat-directed gene targeting of adenoviral vectors to tumor cells.
AB  - Targeting therapeutic gene expression to tumor cells represents a major challenge
      for cancer gene therapy. The strong transcriptional response exhibited by heat
      shock genes, along with the beneficial therapeutic effects of hyperthermia have
      led us to develop a heat-directed gene-targeting strategy for cancer treatment.
      Heat shock gene expression is mediated in large part by the interaction of heat
      shock factor 1 with specific binding sites (heat shock elements; HSE) found in
      the promoters of heat-inducible genes. Here we present a quantitative analysis of
      heat-inducible gene expression mediated by the wild-type hsp70b gene promoter, as
      well as a modified hsp70b promoter containing additional HSE sequences. Beta
      galactosidase (beta-gal) expression was induced between 50- and 800-fold in a
      panel of human breast cancer cell lines infected with an adenoviral vector
      containing the wild-type hsp70b promoter (Ad.70b.betag) following treatment at 43
      degrees C for 30 minutes. Infection with an adenoviral vector containing the
      modified hsp70b promoter (Ad.HSE.70b.betag) resulted in a 200- to 950-fold
      increase in beta-gal expression under the same conditions, and also provided a 1
      2 degrees C decrease in the threshold of activation. Significant increases in the
      heat responsiveness of the Ad.HSE.70b.betag construct were observed in five of
      six tumor cell lines tested, as well as under thermotolerant conditions. Finally,
      we demonstrate that localized heating of a HeLa cell xenograft can effectively
      target beta-gal gene expression following intratumoral injection of Ad.70b.betag.
      Adenoviral vectors incorporating heat-inducible therapeutic genes may provide
      useful adjuncts for clinical hyperthermia.

PMID- 11228536
TI  - An improved intravesical model using human bladder cancer cell lines to optimize
      gene and other therapies.
AB  - Orthotopic implantation of human bladder cancer cells into immunodeficient mice
      is an important tool for studying the biology and effects of therapy.
      Nevertheless, the incidence of tumor implantation and growth by transurethral
      instillation of the human bladder cancer cells into murine bladders has been low
      or not reproducible. However, using a modified intravesical technique and the
      human bladder cancer cell lines, KU-7 and UM-UC-2, we have been able to obtain a
      high and reproducible incidence of superficial bladder tumors. Furthermore,
      intravesical administration of the LacZ adenovirus vector resulted in significant
      beta-galactosidase expression in these bladder tumors as well as the normal
      urothelium, which was associated with the removal of the glycosoaminoglycan
      layer. Because this modified technique produces a high incidence of superficial
      human tumor growth and allows the efficacy of gene transfer to be evaluated, it
      should be a useful model for the study of intravesical gene therapy for human
      bladder cancer.

PMID- 11228537
TI  - Antitumor effects of the combination therapy with TNF-alpha gene-modified tumor
      cells and interleukin 12 in a melanoma model in mice.
AB  - In the present study, TNF-alpha gene-transduced B78 melanoma cells (B78/TNF) were
      used as a vaccine and combined with interleukin (IL)-12 in the treatment of B78
      melanoma-bearing mice. The combined administration of genetically modified
      melanoma cells and IL-12 induced specific protective antitumor immunity resulting
      in a decreased rate of the tumor take following a rechallenge with parental B78
      cells. When used therapeutically, intratumoral injections of irradiated B78/TNF
      melanoma cells and IL-12 exerted strong antitumor effects and led to complete
      regression of established tumors in 50% of mice. Injections of irradiated B78/TNF
      cells alone did not influence tumor development and IL-12 itself significantly
      delayed tumor growth but without curative effect. FACS analysis of parental B78
      melanoma cells and its B78/TNF genetically modified variant showed that a
      proportion of cells of both cell lines expressed 87-1 (CD80) costimulatory
      molecule and that the expression of this molecule was increased during incubation
      with IFN-gamma. Moreover, IFN-gamma markedly augmented expression of major
      histocompatibility class (MHC) class I and II molecules on B78/TNF cells that
      were primarily MHC class I and II negative with no substantial effect on MHC
      negative parental B78 melanoma. IFN-gamma also synergized in cytostatic/cytotoxic
      effects with TNF-alpha against B78 melanoma in vitro. Lymphocyte depletion
      studies in vivo showed reduction of the antitumor response in mice treated with
      anti - NK monoclonal antibodies (mAbs) as well as in mice treated with anti-CD4+
      anti-CD8 mAbs. The results suggest that, when used therapeutically, IL-12 and a
      vaccine containing TNF-alpha gene-transduced tumor cells may reciprocally augment
      their overall antitumor effectiveness by facilitating development of systemic
      antitumor immunity and by stimulating local effector mechanisms of the tumor
      destruction.

PMID- 11228539
TI  - Note from the Editor.

PMID- 11228538
TI  - ABSTRACTS OF ORAL PRESENTATIONS.

PMID- 11228540
TI  - Heightened expression of cyclooxygenase-2 and peroxisome proliferator-activated
      receptor-delta in human endometrial adenocarcinoma.
AB  - Epidemiological studies indicate that nonsteroidal anti-inflammatory drugs
      (NSAIDs) significantly reduce the risk and mortality from colorectal cancer, in
      part by inhibiting prostaglandin (PG) synthesis. Cyclooxygenase (COX), the rate
      limiting enzyme in PG biosynthesis, exists in two isoforms, COX-1 and COX-2.
      Genetic and pharmacological evidence suggest that COX-2 is involved in the
      development of colorectal cancer. We have previously shown that COX-2-derived
      prostacyclin participates in blastocyst implantation through activation of
      peroxisome proliferator activated receptor delta (PPARdelta), a member of the
      nuclear hormone receptor family. Furthermore, our recent studies suggest that a
      similar pathway is operative during colorectal carcinogenesis. These observations
      prompted us to examine whether the COX-2-PPARdelta signaling pathway is also
      involved during development of uterine adenocarcinoma. Here we describe for the
      first time the heightened expression of COX-2 and PPARdelta, but not COX-1, in
      uterine endometrial adenocarcinoma.

PMID- 11228541
TI  - Rapid and quantitative assessment of cancer treatment response using in vivo
      bioluminescence imaging.
AB  - Current assessment of orthotopic tumor models in animals utilizes survival as the
      primary therapeutic end point. In vivo bioluminescence imaging (BLI) is a
      sensitive imaging modality that is rapid and accessible, and may comprise an
      ideal tool for evaluating antineoplastic therapies. Using human tumor cell lines
      constitutively expressing luciferase, the kinetics of tumor growth and response
      to therapy have been assessed in intraperitoneal, and subcutaneous, and
      intravascular cancer models. However, use of this approach for evaluating
      orthotopic tumor models has not been demonstrated. In this report, the ability of
      BLI to noninvasively quantitate the growth and therapeutic-induced cell kill of
      orthotopic rat brain tumors derived from 9L gliosarcoma cells genetically
      engineered to stably express firefly luciferase (9LLuc) was investigated.
      Intracerebral tumor burden was monitored over time by quantitation of photon
      emission and tumor volume using a cryogenically cooled CCD camera and magnetic
      resonance imaging (MRI), respectively. There was excellent correlation (r=0.91)
      between detected photons and tumor volume. A quantitative comparison of tumor
      cell kill determined from serial MRI volume measurements and BLI photon counts
      following 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) treatment revealed that
      both imaging modalities yielded statistically similar cell kill values (P=.951).
      These results provide direct validation of BLI imaging as a powerful and
      quantitative tool for the assessment of antineoplastic therapies in living
      animals.

PMID- 11228542
TI  - Imaging proteolysis by living human breast cancer cells.
AB  - Malignant progression is accompanied by degradation of extracellular matrix
      proteins. Here we describe a novel confocal assay in which we can observe
      proteolysis by living human breast cancer cells (BT20 and BT549) through the use
      of quenched-fluorescent protein substrates. Degradation thus was imaged, by
      confocal optical sectioning, as an accumulation of fluorescent products. With the
      BT20 cells, fluorescence was localized to pericellular focal areas that coincide
      with pits in the underlying matrix. In contrast, fluorescence was localized to
      intracellular vesicles in the BT549 cells, vesicles that also label for lysosomal
      markers. Neither intracellular nor pericellular fluorescence was observed in the
      BT549 cells in the presence of cytochalasin B, suggesting that degradation
      occurred intracellularly and was dependent on endocytic uptake of substrate. In
      the presence of a cathepsin B-selective cysteine protease inhibitor,
      intracellular fluorescence was decreased approximately 90% and pericellular
      fluorescence decreased 67% to 96%, depending on the protein substrate. Matrix
      metallo protease inhibitors reduced pericellular fluorescence approximately 50%,
      i.e., comparably to a serine and a broad spectrum cysteine protease inhibitor.
      Our results suggest that: 1) a proteolytic cascade participates in pericellular
      digestion of matrix proteins by living human breast cancer cells, and 2) the
      cysteine protease cathepsin B participates in both pericellular and intracellular
      digestion of matrix proteins by living human breast cancer cells.

PMID- 11228543
TI  - Aspirin induces apoptosis through release of cytochrome c from mitochondria.
AB  - Nonsteroidal anti-inflammatory drugs (NSAID) reduce the risk for cancer, due to
      their antiproliferative and apoptosis-inducing effects. A critical pathway for
      apoptosis involves the release of cytochrome c from mitochondria, which then
      interacts with Apaf-1 to activate caspase proteases that orchestrate cell death.
      In this study we found that treatment of a human cancer cell line with aspirin
      induced caspase activation and the apoptotic cell morphology, which was blocked
      by the caspase inhibitor zVAD-fmk. Further analysis of the mechanism underlying
      this apoptotic event showed that aspirin induces translocation of Bax to the
      mitochondria and mitochondrial release of cytochrome into the cytosol. The
      release of cytochrome c from mitochondria was inhibited by overexpression of the
      antiapoptotic protein Bcl-2 and cells that lack Apaf-1 were resistant to aspirin
      induced apoptosis. These data provide evidence that the release of cytochrome c
      is an important part of the apoptotic mechanism of aspirin.

PMID- 11228544
TI  - Evaluation of 1p losses in primary carcinomas, local recurrences and peripheral
      metastases from colorectal cancer patients.
AB  - Cytogenetic and molecular genetic analyses of colorectal adenomas and carcinomas
      have shown that loss of the distal part of chromosome arm 1p is common,
      particularly in tumors of the left colon. Because the importance of 1p loss in
      colorectal cancer metastases is unknown, we compared the frequency, exact site
      and extent of 1p deletions in primary carcinomas (n=28), local recurrences (n=19)
      and metastases (n=33) from 67 colorectal cancer patients using 14 markers in an
      allelic imbalance study. Loss of 1p was found in 50% of the primary carcinomas,
      33% of the local recurrences, and 64% of the metastases, revealing a significant
      difference between the local recurrences and the metastases (P=.04). The smallest
      region of 1p deletion overlap (SRO) defined separately for each group of lesions
      had the region between markers D1S2647 and D1S2644, at 1p35-36, in common. The
      genes PLA2G2A (1p35.1-36) and TP73 (1p36.3) were shown to lie outside this
      consistently lost region, suggesting that neither of them are targets for the 1p
      loss. In the second part of the study, microdissected primary carcinomas and
      distant metastases from the same colorectal cancer patients (n=18) were analyzed,
      and the same 1p genotype was found in the majority of patients (12/18, 67%). The
      finding that primary carcinoma cells with metastatic ability usually contain 1p
      deletions, and that some cases lacking 1p alterations in the primary tumor
      acquire such changes during growth of a metastatic lesion, supports the notion
      that 1p loss may be important both early and late in colorectal carcinogenesis,
      with the apparent exception of local recurrences.

PMID- 11228546
TI  - Activation of telomerase rna gene promoter activity by NF-Y, Sp1, and the
      retinoblastoma protein and repression by Sp3.
AB  - Expression of the human telomerase RNA component gene, hTERC is essential for
      telomerase activity. The hTERC gene is expressed during embryogenesis and then
      downregulated during normal development, leaving most adult somatic cells devoid
      of hTERC expression. During oncogenesis, however, hTERC is re-expressed
      consequently contributing to the unrestricted proliferative capacity of many
      human cancers. Thus the identification of the molecular basis for the regulation
      of the telomerase RNA component gene in normal cells and its deregulation in
      cancer cells is of immediate interest. We have previously cloned the hTERC
      promoter and in this study have identified several transcription factors that
      modulate the expression of hTERC. We demonstrate that NF-Y binding to the CCAAT
      region of the hTERC promoter is essential for promoter activity. Sp1 and the
      retinoblastoma protein (pRb) are activators of the hTERC promoter and Sp3 is a
      potent repressor. These factors appear to act in a species-specific manner.
      Whereas Sp1 and Sp3 act on the human, bovine, and mouse TERC promoters, pRb
      activates only the human and bovine promoter, and NF-Y is only essential for the
      human TERC gene.

PMID- 11228545
TI  - Posttranscriptional regulation of cyclooxygenase-2 in rat intestinal epithelial
      cells.
AB  - Modulation of cyclooxygenase-2 (COX-2) mRNA stability plays an important role in
      the regulation of its expression by oncogenic Ras. Here, we evaluate COX-2 mRNA
      stability in response to treatment with two known endogenous promoters of
      gastrointestinal cancer, the bile acid (chenodeoxycholate; CD) and ceramide.
      Treatment with CD and ceramide resulted in a 10-fold increase in the level of COX
      2 protein and a four-fold lengthening of the half-life of COX-2 mRNA. COX-2 mRNA
      stability was assessed by Northern blot analysis and by evaluating the AU-rich
      element located in the COX-2 3'-UTR. A known inhibitor of mitogen-activated
      protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK), PD98059,
      reversed the effects of CD or ceramide to stabilize COX-2 mRNA. Overexpression of
      a dominant-negative ERK-1 or ERK-2 protein also led to destabilization of COX-2
      mRNA. Treatment with a p38 MAPK inhibitor, PD169316, or transfection with a
      dominant-negative p38 MAPK construct reversed the effect of CD or ceramide to
      stabilize COX-2 mRNA. Expression of a dominant-negative c-Jun N-terminal kinase
      (JNK) had no effect on COX-2 mRNA stability in cells treated with CD or ceramide.
      We conclude that posttranscriptional mechanisms play an important role in the
      regulation of COX-2 expression during carcinogenesis.

PMID- 11228547
TI  - The relationship between spontaneous telomere loss and chromosome instability in
      a human tumor cell line.
AB  - Chromosome instability plays an important role in cancer by promoting the
      alterations in the genome required for tumor cell progression. The loss of
      telomeres that protect the ends of chromosomes and prevent chromosome fusion has
      been proposed as one mechanism for chromosome instability in cancer cells,
      however, there is little direct evidence to support this hypothesis. To
      investigate the relationship between spontaneous telomere loss and chromosome
      instability in human cancer cells, clones of the EJ-30 tumor cell line were
      isolated in which a herpes simplex virus thymidine kinase (HSV-tk) gene was
      integrated immediately adjacent to a telomere. Selection for HSV-tk-deficient
      cells with ganciclovir demonstrated a high rate of loss of the end these "marked"
      chromosomes (10-4 events/cell per generation). DNA sequence and cytogenetic
      analysis suggests that the loss of function of the HSV-tk gene most often
      involves telomere loss, sister chromatid fusion, and prolonged periods of
      chromosome instability. In some HSV-tk-deficient cells, telomeric repeat
      sequences were added on to the end of the truncated HSV-tk gene at a new
      location, whereas in others, no telomere was detected on the end of the marked
      chromosome. These results suggest that spontaneous telomere loss is a mechanism
      for chromosome instability in human cancer cells.

PMID- 11228548
TI  - Use of arsenic trioxide as an antivascular and thermosensitizing agent in solid
      tumors.
AB  - Arsenic trioxide, As2O3 (ATO), has been found to be an effective chemotherapeutic
      for acute promyelocytic leukemia but its effect on solid tumors has not been
      fully explored. In the present report, we describe our observation that ATO is a
      potent antivascular agent and that it markedly enhances the effect of
      hyperthermia on tumors. The tumor blood perfusion in SCK tumors of A/J mice and
      FSaII tumors of C3H mice was significantly suppressed for up to 24 hours after an
      i.p. injection of 8 mg/kg ATO. ATO was also found to be able to increase the
      thermosensitivity of tumor cells in vitro. As a probable consequence of these
      effects, ATO treatment markedly increased the tumor growth delay caused by
      hyperthermia at 41.5 to 42.5 degrees C. Immunohistochemical staining of tumor
      tissue revealed that the expression levels of several adhesion molecules and
      TNFalpha are noticeably increased in tumors 2 to 6 hours after systemic ATO
      treatment. It is concluded that ATO is potentially useful to enhance the effect
      of hyperthermia on tumors at a clinically relevant temperature.

PMID- 11228566
TI  - End-of-life care in the intensive care unit: where are we now?
AB  - A growing body of evidence and experience has effaced what were once thought to
      be clear distinctions between "critical illness" and "terminal illness" and has
      exposed the problems of postponing palliative care for intensive care patients
      until death is obviously imminent. Integration of palliative care as a component
      of comprehensive intensive care is now seen as more appropriate for all
      critically ill patients, including those pursuing aggressive treatments to
      prolong life. At present, however, data on which to base practice in this
      integrated model remain insufficient, and forces of the healthcare economy and
      other factors may constrain its application. The purpose of this article is to
      map where we are now in seeking to improve palliative care in the intensive care
      unit. We review existing evidence, which suggests that both symptom management
      and communication about preferences and goals of care warrant improvement and
      that prevailing practices for limitation of life-sustaining treatments are
      inconsistent and possibly irrational. We also address the need for assessment
      tools for research and quality improvement. We discuss recent initiatives and
      ongoing obstacles. Finally, we identify areas for further exploration and suggest
      guiding principles.

PMID- 11228549
TI  - Expression of interleukin-8 promotes neutrophil infiltration and genetic
      instability in mutatect tumors.
AB  - Neutrophils represent a potential source of genotoxic reactive oxygen and
      nitrogen species in the tumor microenvironment. Using Mutatect cell lines, which
      can form subcutaneous tumors in syngeneic C57BL/6 mice, we have previously
      established that the number of spontaneously infiltrating neutrophils correlates
      with the number of mutations at the hypoxanthine phosphoribosyltransferase (Hprt)
      locus. We now describe the properties of four lines that express different levels
      of the neutrophil chemokine, interleukin-8 (IL-8), from a tetracycline (TET)
      responsive promoter. In a series involving 45 animals, IL-8-expressing lines
      produced tumors with a higher neutrophil content than the control line. Analysis
      of the 45 tumors revealed that the neutrophil level again strongly correlated
      with hprt mutant frequency (MF) (P<.0001, r=0.88). Administration of TET was
      effective in lowering the neutrophil content of low IL-8-expressing tumors, but
      not high IL-8-expressing tumors. Although the IL-8 transgene was stable in all
      lines in vitro, high IL-8-expressing lines completely lost the transgene in vivo
      whereas low IL-8-expressing lines showed no evidence of transgene instability.
      These results provide further evidence, based on the study of an endogenous gene
      (hprt) and an IL-8 transgene, that neutrophils may contribute to genetic
      instability in tumors.

PMID- 11228567
TI  - Communication in intensive care settings: the challenge of futility disputes.
AB  - In intensive care settings, suboptimal communication can erode family trust and
      fuel so-called "futility" disputes. Presenting a teaching case used by >225
      hospitals participating in the Decisions Near the End-of-Life program, we
      identify critical communication challenges and opportunities. We emphasize that
      good communication requires not only clear and sensitive language but also
      clinician self-awareness, psychological insight, and an institutional culture
      that promotes good communication with families. The article concludes with two
      examples of steps institutions can take to foster good communication between
      families and healthcare professionals.

PMID- 11228568
TI  - Educational agendas for interdisciplinary end-of-life curricula.
AB  - The importance of an interdisciplinary end-of-life curricula for the intensive
      care unit is now recognized. Educational agendas for interdisciplinary end-of
      life curricula are being developed across the United States. However, the limited
      database on palliative care education precludes evidence-based recommendations.
      Through a case-based approach, the need for an interdisciplinary team is
      explored, including the definition of an interdisciplinary team and the step-wise
      incorporation of specific members, such as physicians, nurses, social workers,
      and the chaplain, as patient care evolves. Core competencies for end-of-life care
      are enumerated including the approaches to end-of-life care, ethical and legal
      constraints, symptom management, specific end-of-life syndromes/palliative
      crises, and development of communication skills for trusting relationships.
      Finally, four phases of ICU management of curative and comfort care are proposed:
      phase I, focus on checklist for transfer; phase II, focus on life-saving
      treatments; phase III, focus on the "whole" patient; and phase IV, focus on
      palliative care.

PMID- 11228569
TI  - Patient autonomy versus parentalism.
AB  - Several decision-making models have been advanced to characterize the patient
      physician relationship. These include the parental model, the informed decision
      making model, the interpretive model, and the deliberative model. Although these
      models are useful to consider in reflecting on the care we give to critically ill
      patients at the end of life, they require adaptation to the intensive care unit
      (ICU). Many clinicians adapt their approach to each individual patient and change
      their approach to the same patient over time. Moreover, instead of the dyadic
      model of one patient and one physician, multiple voices often speak for the
      patient and a team of clinicians care for the ICU patient. Analysis of human
      relationships and communication with critically ill patients and their families
      require transdisciplinary, multicultural, and multidisciplinary interpretation.

PMID- 11228570
TI  - The family conference as a focus to improve communication about end-of-life care
      in the intensive care unit: opportunities for improvement.
AB  - The intensive care unit (ICU) represents a hospital setting in which death and
      discussion about end-of-life care are common, yet these conversations are often
      difficult. Such difficulties arise, in part, because a family may be facing an
      unexpected poor prognosis associated with an acute illness or exacerbation and,
      in part, because the ICU orientation is one of saving lives. Understanding and
      improving communication about end-of-life care between clinicians and families in
      the ICU is an important focus for improving the quality of care in the ICU. This
      communication often occurs in the "family conference" attended by several family
      members and members of the ICU team, including physicians, nurses, and social
      workers. In this article, we review the importance of communication about end-of
      life care during the family conference and make specific recommendations for
      physicians and nurses interested in improving the quality of their communication
      about end-of-life care with family members. Because excellent end-of-life care is
      an important part of high-quality intensive care, ICU clinicians should approach
      the family conference with the same care and planning that they approach other
      ICU procedures. This article outlines specific steps that may facilitate good
      communication about end-of-life care in the ICU before, during, and after the
      conference. The article also provides direction for the future to improve
      physician-family and nurse-family communication about end-of-life care in the ICU
      and a research agenda to improve this communication. Research to examine and
      improve communication about end-of-life care in the ICU must proceed in
      conjunction with ongoing empiric efforts to improve the quality of care we
      provide to patients who die during or shortly after a stay in the ICU.

PMID- 11228571
TI  - Advance care planning: pitfalls, progress, promise.
AB  - We now have a decade of experience with advance directives since the Patient Self
      Determination Act was signed into law in November 1990. With few exceptions,
      empirical studies have yielded disappointing results. Advance directives are
      recorded by medical personnel more often but are not completed by patients more
      frequently. The process of recording them does not enhance patient-physician
      communication. When available, advance directives do not change care or reduce
      hospital resources. The most ambitious study of advance care planning, the Study
      to Understand Prognoses and Preferences for Outcomes and Risks of Treatments,
      failed to show any change in outcomes after an extensive intervention.
      Investigators have attempted to identify the reasons why the optimism about the
      Patient Self-Determination Act has not been realized. Many interventions to
      facilitate advance care planning were focused on specific treatment decisions.
      Recent research suggests that preferences for care are not fixed but emerge in a
      clinical context from a process of discussion and feedback within the network of
      the patient's most important relationships. Clinical trials emphasizing this
      approach have been successful. The approach that emphasizes communication,
      building trust over time, and working within the patient's most important
      relationships offers a hopeful model for clinicians working in intensive care
      units.

PMID- 11228572
TI  - End-of-life care: what do the American courts say?
AB  - End-of-life care of critically ill patients generally consists of two closely
      related practices: the withholding and withdrawal of life support, and the
      administration of palliative care. In the United States, the withholding or
      withdrawal of life support is legally justified by the principles of informed
      consent and informed refusal. The U.S. Supreme Court has held that competent
      patients may refuse any and all treatments, including those that sustain life.
      All states sanction such refusal by competent patients, and most states allow
      surrogates to refuse treatment on behalf of incompetent patients. Although some
      physicians use the concept of futility to unilaterally withhold or withdraw life
      support, the Supreme Court has not heard a futility case, and the only clear
      legal rule on futile treatment is the traditional malpractice test, which
      measures physician actions against standards of medical care. However, the
      Supreme Court has furnished guidelines on the administration of palliative care.
      By using the principle of double effect, these guidelines allow physicians to
      give sedative and analgesic agents to dying patients if they intend to relieve
      pain and suffering but not to hasten death.

PMID- 11228573
TI  - Economics of end-of-life care in the intensive care unit.
AB  - End-of life care is in need of improvement, yet little is known about the
      effectiveness or cost of various end-of-life therapies. Economic analyses are
      used to help make decisions between two or more therapies when resources are
      constrained. In this chapter, we review the various types of economic analyses,
      the costs of dying, and how healthcare reform has impacted these costs. Finally,
      we discuss the unique issues associated with cost-effectiveness studies of
      palliative therapy, with emphasis on the problem of calculating a cost
      effectiveness ratio when there is no good measurement for valuing the quality of
      death. It is likely that methods for conducting a cost-effectiveness analyses for
      end-of-life care will need to evolve or alternative strategies such as cost
      benefit analysis or distributive justice will be needed to inform resource
      allocation decisions. As the national debate about healthcare costs, access, and
      quality continues, we will increasingly turn to economic analyses to help make
      resource allocation decisions. Cost-effectiveness analysis will continue to be
      the most popular form of economic analysis because it combines the results
      (effectiveness of treatment) with the costs of achieving the results. We must be
      aware of the limitations of cost-effectiveness analyses and the need for value
      judgments when using cost-effectiveness analyses to inform healthcare decisions.

PMID- 11228574
TI  - Cultural differences in end-of-life care.
AB  - The exact time of death for many intensive care unit patients is increasingly
      preceded by an end-of-life decision. Such decisions are fraught with ethical,
      religious, moral, cultural, and legal difficulties. Key questions surrounding
      this issue include the difference between withholding and withdrawing, when to
      withhold/withdraw, who should be involved in the decision-making process, what
      are the relevant legal precedents, etc. Cultural variations in attitude to such
      issues are perhaps expected between continents, but key differences also exist on
      a more local basis, for example, among the countries of Europe. Physicians need
      to be aware of the potential cultural differences in the attitudes not only of
      their colleagues, but also of their patients and families. Open discussion of
      these issues and some change in our attitude toward life and death are needed to
      enable such patients to have a pain-free, dignified death.

PMID- 11228575
TI  - End-of-life care in the intensive care unit: can we do better?
AB  - Everywhere we turn these days, it seems that we are confronted with a new study
      that reports the dissatisfaction expressed by families with the quality of care
      received by their loved ones who have died while in the intensive care unit. It
      is difficult for caregivers to accept this information, which is now commonly
      reported both in published studies and in the lay press. As clinicians, most of
      us believe that we truly care about our patients and are trying, as best we can,
      to act in their best interest. No caregiver wants to hear that he or she does not
      do a good job when caring for dying patients and their families. It is ironic
      that clinicians recognize and accept the need for continuing education. Yet many
      clinicians resent the suggestion that the skills required for end-of-life care
      might be viewed in the same manner, as a lifelong learning process. It is unusual
      for physicians to identify end-of-life-care as an area of competency that can be
      improved or updated. Perhaps this is why end-of-life-care has been so difficult
      to teach to clinicians in training. Although many medical schools offer courses
      on the ethics of death and dying, formal training in end-of-life care skills is
      not routinely given in most postgraduate training programs. Learning these skills
      is a matter of on-the-job training for most caregivers. Not only have we been
      unable to measure any beneficial impact from education initiatives for end-of
      life care, we have yet to identify clear indicators for end-of-life care. For
      caregivers, enhancing end-of-life skills may be a matter of improved listening
      skills, attention to the proper environment for end-of-life discussions, and a
      willingness to facilitate end-of-life decision-making. Encouraging caregivers to
      view end-of-life skills as a lifelong educational process, identifying core
      competencies in end-of-life care, and training clinicians in these skills are the
      challenges for the future. The quality of care our patients receive at the end of
      life will depend on our ability to answer these difficult questions.

PMID- 11228576
TI  - Contrast medium-induced pulmonary vascular hyperpermeability is aggravated in a
      rat climacterium model.
AB  - Tominaga K, Kataoka Y, Sendo T, et al. Contrast medium-induced pulmonary vascular
      hyperpermeability is aggravated in a rat climacterium model. Invest Radiol
      2001;36:131-135. RATIONALE AND OBJECTIVES: To test whether climacterium
      influences adverse pulmonary reactions to contrast media, the authors
      investigated the effect of ioxaglate on pulmonary vascular permeability in
      ovariectomized rats as a climacterium model. METHODS: From 7 days after surgery,
      ovariectomized rats were treated with estradiol valerate or vehicle once per week
      for 3 weeks. At 28 days after surgery, ioxaglate, an ionic contrast medium, was
      intravenously injected at 1.5 mL/min in rats. Pulmonary vascular permeability was
      evaluated by measuring the amount of Evans blue dye in the lung tissue. RESULTS:
      Ioxaglate dose-dependently increased pulmonary vascular permeability in sham
      operated and ovariectomized rats. Ovariectomized rats showed a 2.6-fold increased
      aggravation of vascular permeability by ioxaglate 4 g I/kg compared with sham
      operated rats. Estradiol valerate (0.2-5.0 mg/kg) dose-dependently blocked
      ioxaglate-increased vascular permeability in ovariectomized rats. CONCLUSIONS:
      These findings suggest that climacterium is included, at least in part, in the
      risk factors for contrast-induced adverse pulmonary reactions, and this risk is
      lowered by estrogen replacement therapy.

PMID- 11228577
TI  - Potential of Gd-DTPA-mannan liposome particles as a pulmonary perfusion MRI
      contrast agent: an initial animal study.
AB  - Suga K, Mikawa M, Ogasawara N, et al. Potential of Gd-DTPA-mannan liposome
      particles as a pulmonary perfusion MRI contrast agent: An initial animal study.
      Invest Radiol 2001;36:136-145. RATIONALE AND OBJECTIVES: A paramagnetic, particle
      type MR contrast agent, (Gd-diethylenetriamine pentaacetic acid [DTPA]-mannan
      cholesterol)-coated liposomes, was designed to localize in the lung by the
      mechanism of capillary blockade, and the potential of this agent for pulmonary
      perfusion MRI was experimentally investigated. METHODS: Before and up to 60
      minutes after slow injection of this contrast agent, MR images were sequentially
      acquired at 10-second intervals along the same transaxial plane of the lung by
      using a gradient-echo pulse sequence with a short echo time of 1.2 ms on a 1.5-T
      MR scanner. After the minimal dose for obtaining a sufficient lung enhancement
      effect was determined in five rabbits, the time course of the enhancement effect
      was evaluated in six dogs by arterial blood gas analysis. The efficacy of MRI for
      detecting perfusion defects was evaluated in seven other dogs with pulmonary
      embolism. RESULTS: Normal lungs were dose-dependently enhanced by this agent, and
      with a 2.0 mL/kg dose, dependent lungs were enhanced by more than 201%, with an
      average half-life of the enhancement effect of 35.7 +/- 5.3 minutes. With less
      than this dose (1.0-1.5 mL/kg), all of the embolized lung portions were clearly
      identified as perfusion defects. The prolonged enhancement effect allowed the
      acquisition of subsequent multisectional lung images, thus facilitating the
      assessment of anatomic location and extent of the perfusion defects. The
      reduction of PaO2 in room air after injection was within 5 mm Hg in both normal
      and embolized animals. CONCLUSIONS: These initial, experimental results show that
      paramagnetically labeled liposome particles may be a successful MR contrast agent
      for pulmonary perfusion imaging.

PMID- 11228578
TI  - Cerebrospinal fluid flow waveforms: MR analysis in chronic adult hydrocephalus.
AB  - Henry-Feugeas MC, Idy-Peretti I, Baledent O, et al. Cerebrospinal fluid flow
      waveforms: MR analysis in chronic adult hydrocephalus. Invest Radiol 2001;36:146
      154. RATIONALE AND OBJECTIVES: To analyze changes in cerebrospinal fluid (CSF)
      hydrodynamics in chronic adult hydrocephalus. METHODS: Phase-contrast cine-MR
      acquisitions were used to explore the ventricular system and the upper ventral
      cervical spaces of 16 patients. The aqueductal jet was explored in 32 control
      subjects. RESULTS: The duration of pulsatile caudal CSF flow (ie, CSF systole)
      was abnormally short in patients with active idiopathic and obstructive
      hydrocephalus. The duration of CSF cervical systole was normal in patients with
      stable hydrocephalus. The aqueductal stroke volume could be increased in stable
      communicating hydrocephalus. Patients who responded to shunting had shortened CSF
      systoles and hyperpulsatile ventricular patterns. Successful CSF diversion
      resulted in longer CSF systoles and CSF ventricular patterns that were no longer
      hyperpulsatile. CONCLUSIONS: Magnetic resonance analysis of CSF flow can show
      craniospinal dissociation and limitation of CSF outflow from the ventricles in
      both obstructive and communicating hydrocephalus; it should help determine the
      response to shunting in communicating hydrocephalus.

PMID- 11228579
TI  - Comparison of metabolite levels and water diffusion between cortical and
      subcortical strokes as monitored by MRI and MRS.
AB  - Labelle M, Khiat A, Durocher A, et al. Comparison of metabolite levels and water
      diffusion between cortical and subcortical strokes as monitored by MRI and MRS.
      Invest Radiol 2001;36:155-163. RATIONALE AND OBJECTIVES: Proton magnetic
      resonance spectroscopy (MRS) and functional imaging techniques are increasingly
      recognized as useful tools for the characterization of strokes. The aim of this
      study was to compare cortical and subcortical (lacunar) strokes by MRS and
      diffusion-weighted imaging (DWI) experiments as a function of time. METHODS:
      Single-voxel MRS, DWI, and perfusion-weighted imaging data were recorded on
      patients with cortical (n = 7) or subcortical (n = 7) strokes in the acute,
      subacute, and chronic periods. Magnetic resonance spectra were acquired in three
      regions: hyperintense DWI area, adjacent area with normal DWI intensity, and
      contralateral area. Neurological deficits were estimated by the National
      Institutes of Health Stroke Scale. RESULTS: Decreases in N-acetylaspartate,
      choline-containing compounds, and creatine/phosphocreatine signal intensity as
      well as the presence of lactate were observed at all times in the hyperintense
      DWI area of all lesions. Small decreases were measured in the subacute and
      chronic phases for the adjacent area of cortical strokes but not for the adjacent
      area of subcortical strokes. The existence of a surrounding affected area in
      subcortical strokes is deduced from a combination of MRS and DWI results,
      possibly corresponding to the ischemic penumbra. Differences were found between
      the two types of lesion, especially an increased time variability of apparent
      diffusion coefficients in subcortical strokes. CONCLUSIONS: Magnetic resonance
      spectroscopy provides evidence for the existence of affected tissue outside the
      hyperintense DWI regions in subcortical strokes. Cortical and subcortical strokes
      display different DWI and MRS characteristics.

PMID- 11228580
TI  - Evaluation of CT time-density curves of lower-limb veins.
AB  - Szapiro D, Ghaye B, Willems V, et al. Evaluation of CT time-density curves of
      lower-limb veins. Invest Radiol 2001;36:164-169. RATIONALE AND OBJECTIVES: To
      evaluate time-density curves of the lower-limb veins for optimization of CT
      venography. METHODS: Fifty patients referred for chest CT were randomized into
      five equal groups. Five anatomic levels (abdomen, pelvis, proximal thigh, knee,
      and midcalf) were evaluated by a dynamic acquisition during 7 minutes. Computed
      tomography attenuation values of the veins, arteries, and adjacent muscles were
      measured for each level and plotted into curves versus time. Venous enhancement
      was also assessed qualitatively. RESULTS: Mean peak enhancement values of the
      inferior vena cava and the iliac, femoral, popliteal, anterior tibial, posterior
      tibial, and peroneal veins were, respectively, 112 +/- 16, 103 +/- 17, 93 +/- 23,
      98 +/- 30, 112 +/- 28, 137 +/- 28, and 124 +/- 29 Hounsfield units. These were
      reached at 93 +/- 9.5, 129 +/- 15, 135 +/- 20, 147 +/- 57, 124 +/- 32, 123 +/-
      17, and 123 +/- 18 seconds. Homogeneous opacification was obtained after 210
      seconds. An optimal time window for CT venography was obtained between 210 and
      240 seconds for the calf level and between 180 and 300 seconds for above-knee
      veins. CONCLUSIONS: For sequential CT venography, a caudocranial acquisition of
      the lower-limb veins, starting at 210 seconds, should allow optimal clot
      detection.

PMID- 11228581
TI  - Contrast-enhanced peripheral MR angiography from the abdominal aorta to the pedal
      arteries: combined dynamic two-dimensional and bolus-chase three-dimensional
      acquisitions.
AB  - Wang Y, Winchester PA, Khilnani NM, et al. Contrast-enhanced peripheral MR
      angiography from the abdominal aorta to the pedal arteries: Combined dynamic two
      dimensional and bolus-chase three-dimensional acquisitions. Invest Radiol
      2001;36:170-177. RATIONALE AND OBJECTIVES: To obtain reliable contrast-enhanced
      peripheral MR angiography for imaging peripheral vascular disease from the
      abdominal aorta to the pedal arteries. METHODS: A protocol consisting of contrast
      enhanced, dynamic two-dimensional (2D) acquisition at the feet and calf and bolus
      chase three-dimensional (3D) acquisition from the abdominal aorta to the calf was
      developed and applied in patients with peripheral vascular disease. The
      performance of this integrated protocol was assessed in 89 consecutive patients.
      RESULTS: The bolus-chase 3D acquisition was of diagnostic quality in 100% of the
      acquisitions in the abdomen, 96% in the thigh, and 43% in the calf. The poor
      quality of the calf acquisitions was due to insufficient spatial resolution, poor
      arterial signal, and venous contamination. Diagnostic-quality images were
      obtained in 100% of the dynamic 2D acquisitions of the calf and 98% of the feet.
      CONCLUSIONS: The combined dynamic 2D and bolus-chase 3D contrast-enhanced MR
      angiography technique provides diagnostic images of the entire lower extremity.

PMID- 11228583
TI  - Radiologic anatomy of the rabbit liver on hepatic venography, arteriography,
      portography, and cholangiography.
AB  - Seo TS, Oh JH, Lee DH, et al. Radiologic anatomy of the rabbit liver on hepatic
      venography, arteriography, portography, and cholangiography. Invest Radiol
      2001;36:186-192. RATIONALE AND OBJECTIVES: The radiologic anatomy of rabbit liver
      has received little study but is important in many experimental investigations.
      METHODS: Twenty-four rabbits were studied by using hepatic venograms, aortograms,
      hepatic arteriograms, cholangiograms, and portograms. RESULTS: In all cases, the
      right, middle, and left hepatic veins drained into the inferior vena cava just
      below the diaphragm, and the caudate lobe hepatic vein drained more inferiorly.
      The proper hepatic artery was a branch of the common hepatic artery in 96%. The
      first branch of the proper hepatic artery was the caudate lobe artery. The
      remaining main hepatic artery was divided into the right and left hepatic
      arteries. The left hepatic artery was further divided into the medial and lateral
      segmental branches in 95%. The anatomy of the portal vein or bile duct was the
      same as the hepatic artery in 100% of cases. CONCLUSIONS: Knowledge of the normal
      patterns and variations of the vessels and bile duct will be helpful for
      experiments of the rabbit liver in future studies.

PMID- 11228582
TI  - Compartmental modeling of technetium-99m-labeled teboroxime with dynamic single
      photon emission computed tomography: comparison with static thallium-201 in a
      canine model.
AB  - Di Bella EVR, Ross SG, Kadrmas DJ, et al. Compartmental modeling of technetium
      99m-labeled teboroxime with dynamic single-photon emission computed tomography:
      Comparison with static thallium-201 in a canine model. Invest Radiol 2001;36:178
      185. RATIONALE AND OBJECTIVES: A compartmental modeling approach to deriving
      kinetic parameters from a time series of single-photon emission computed
      tomography (SPECT) images of technetium-99m-labeled (99mTc-) teboroxime may have
      value for semiquantitative assessment of myocardial perfusion. This study
      investigated the value of the kinetic parameters derived from a two-compartment
      model of 99mTc-teboroxime for measuring myocardial perfusion and compared it with
      static thallium-201 (201Tl) uptake and microsphere-measured blood flow in dogs.
      METHODS: Experiments were successfully conducted in 9 of 11 open-chest dogs.
      During adenosine stress, a single complete set of projections of 201Tl uptake was
      acquired. 99mTc-teboroxime was then injected during adenosine stress, and a
      complete set of projections was acquired every 5.7 seconds for 17 minutes.
      Resting studies were performed on 4 of the animals. All of the projection sets
      were reconstructed with an iterative algorithm and incorporated corrections for
      attenuation and the geometric response of the collimators. Regional kinetic
      parameters (washin and washout) were determined semiautomatically from the time
      series of reconstructed 99mTc-teboroxime images and registered with microsphere
      data. Regional washin estimates were compared with 201Tl intensities and
      myocardial blood flows determined from microspheres. RESULTS: Optimally scaled
      99mTc-teboroxime washin parameters and 201Tl uptakes were correlated with
      microsphere-determined blood flows (r = 0.91, y = 0. 99x + 0.01, and r = 0.92, y
      = 0.88x + 0.28, respectively). In six of the studies, the left anterior
      descending coronary artery was occluded, and stress occluded-to-normal (O/N)
      ratios were calculated. The O/N ratios were 0.32 +/- 0.17 as determined from
      microspheres injected with 201Tl and 0.38 +/- 0.29 from microspheres injected
      with 99mTc-teboroxime (P = NS). The O/N ratios were 0.48 +/- 0.16 for static
      201Tl uptake and 0.27 +/- 0.21 for 99mTc-teboroxime washin (P < 0.05).
      CONCLUSIONS: Both 201Tl uptake and 99mTc-teboroxime kinetic parameters were well
      correlated with flow. The 99mTc-teboroxime washin parameters offer
      semiquantitative flow values and provide greater defect contrast than can be
      obtained with 201Tl uptake values.

PMID- 11228585
TI  - Mark-recapture and Moran curve estimates of the survival probabilities of an
      island population of tsetse flies Glossina morsitans morsitans (Diptera:
      Glossinidae).
AB  - A study on populations of Glossina morsitans morsitans Westwood on Antelope
      Island, Lake Kariba, Zimbabwe provided Jolly-Seber (J-S) mark-recapture estimates
      of adult survival and Moran curve estimates of the overall survival of all
      developmental stages. For females, Moran survival estimates derived using ox fly
      round catches showed similar trends to, but were more variable than, those
      calculated from J-S population estimates. Regression of one set on the other
      removed only 26% of the variance. Undue emphasis should not be placed on small
      changes in Moran survival estimates based on sequences of catches. Catch data
      cannot provide Moran estimates of male survival probabilities and no comparison
      is thus possible with estimates from the J-S data. The J-S and the Moran
      approaches were combined to estimate survival probabilities of the immature
      stages of male and female tsetse. The overall survival per three-week period
      averaged 45% for males and 59% for females, comprising mature adult survivals of
      27 and 46%, and pooled survivals of immature stages of 59 and 77%, respectively.
      The high survival of immature flies is due to the sheltered, inactive nature of
      pupal life. Adult and overall survival probabilities were highly correlated in
      males (r(2) = 0.61) but less so in females (r(2) = 0.24) where capture rates were
      lower and variance in the results greater. Immature and overall survival was more
      highly correlated for both sexes, with r(2) = 0.77 and 0.53 for males and females
      respectively. When a fixed pupal mortality of 1% per day was assumed, estimates
      of the survival of young adult males suggested that these were even lower than
      the survival of mature flies at the harshest times of the year, but were not
      markedly different when overall survival was high. Assuming equal mortality in
      all adults enabled the estimation of pupal survival. These had high variances but
      there was no evidence of any difference between the survival probabilities of
      male and female pupae.

PMID- 11228586
TI  - Carbamate and organophosphate resistance in cotton pests in India, 1995 to 1999.
AB  - Monitoring for organophosphate and carbamate resistance was carried out on five
      major insect pests of cotton collected from 22 cotton-growing districts across
      India. Resistance was monitored in Helicoverpa armigera (Hubner) and Pectinophora
      gossypiella (Saunders) for the period 1995-1999 and for Spodoptera litura
      (Fabricius), Earias vittella (Fabricius) and Bemisia tabaci (Gennadius) in a
      survey conducted during the 1997-98 cropping season. Of the 53 field strains of
      H. armigera, only four were found to exhibit resistance to quinalphos, the
      highest 15-fold, whereas all 16 field strains tested were found to be resistant
      to monocrotophos. Similarly, out of 40 field strains tested, only eight were
      found to express appreciable resistance to methomyl. Resistance in P. gossypiella
      to quinalphos was high in the majority of the strains tested. Of the seven
      strains of E. vittella tested, two strains from northern India exhibited > 70
      fold resistance to monocrotophos. Of the 11 S. litura strains tested, only four
      were found to exhibit resistance factors of 10 to 30-fold to quinalphos and
      monocrotophos. All of the B. tabaci field strains exhibited resistance to
      methomyl and monocrotophos and susceptibility to triazophos. Practical
      implications for pest control resulting from the observed patterns of cross
      resistance between quinalphos, monocrotophos and methomyl are discussed.

PMID- 11228587
TI  - Effect of temperature and cultivar on pea aphid, Acyrthosiphon pisum (Hemiptera:
      Aphididae) life history.
AB  - Life history parameters of the pea aphid, Acyrthosiphon pisum were studied at
      five constant temperatures on two cultivars of peas, Scout and Sancho. The
      development and mortality of juveniles and the life-span, age-specific fecundity
      and survivorship of adult aphids were recorded and used to construct life tables.
      The juvenile development period (from birth to adulthood) was longest at 11.9
      degrees C (16.8 days on cv. Scout and 16.2 days on cv. Sancho) and shortest at
      26.7 degrees C (8.5 days on cv. Scout and 8.8 days on cv. Sancho). At all
      temperatures, except 26.7 degrees C, juveniles developed faster on cv. Sancho
      than on cv. Scout. On both pea varieties juvenile mortality was highest at
      temperatures above 19.6 degrees C and lowest at 19.6 degrees C. Highest
      cumulative juvenile mortality was recorded on cv. Scout at 26.7 degrees C when
      only 9% of aphids survived from birth to reproductively mature adults. Fecundity
      rates were unaffected by temperature in the range tested on cv. Sancho but
      increased with increasing temperatures between 11.9 and 19.6 degrees C on cv.
      Scout. These differences in life history parameters were reflected in the
      population growth (rm) of aphids on both pea cultivars which increased with
      increasing temperatures between 11.9 and 23.1 degrees C on cv. Sancho and 11.9
      and 19.6 degrees C on cv. Scout, declining thereafter. Population growth was
      consistently greater at all temperatures for aphids reared on cv. Sancho than
      those reared on cv. Scout.

PMID- 11228588
TI  - Coexistence of two effective parasitoids of the white peach scale Pseudaulacaspis
      pentagona (Hemiptera: Diaspididae): the role of host stage and temperature.
AB  - ENCARSIA BERLESEI: (Howard) and Pteroptrix orientalis (Silvestri) are
      endoparasitoids of Pseudaulacaspis pentagona (Targioni Tozzetti), that are
      sympatric in Campania (Italy). The influence of host stages on several components
      of E. berlesei fitness and the effect of mating status on the production of
      Pteroptrix orientalis progeny were evaluated at 25 degrees C. Parasitization of
      earlier host stages resulted in an increase in the development time and a
      decrease in progeny number of E. berlesei. Adult parasitoids were largest when
      young female stages were parasitized. Pupal mortality did not differ among host
      stages. Mated female P. orientalis produced a greater number of progeny and
      proportionally fewer sons (13.6% of the total progeny) than did virgin females
      (21.7%). The reproductive potential of both parasitoids was also evaluated at
      four regimes of constant temperature (20, 24, 26 and 30 degrees C). Encarsia
      berlesei attained rm values nearly double those of P. orientalis at 20, 24 and 26
      degrees C, whilst at 30 degrees C the two parasitoids achieved the same rm value,
      since at this temperature E. berlesei suffered a high pupal mortality. Sex ratio
      of P. orientalis, expressed as proportion of males, varied significantly between
      20 and 24 degrees C only.

PMID- 11228589
TI  - Plant species modifies the functional response of Phytoseiulus persimilis (Acari:
      Phytoseiidae) to Tetranychus urticae (Acari: Tetranychidae): implications for
      biological control.
AB  - The functional response of the predatory mite Phytoseiulus persimilis Athias
      Henriot to eggs of its prey, the spider mite Tetranychus urticae Koch was
      examined on three plant species. Experiments were done to determine whether
      differences in the functional response on the three plant species were due to the
      morphological features of the crop directly on the predator or through an effect
      of the plant species on the prey. The results show that crop morphology is the
      only factor influencing the predatory ability of P. persimilis on the three plant
      species. Fewer eggs were eaten on Ceanothus thyrsiflorus var. 'Autumnal Blue',
      the plant species with hairy leaves, and greater numbers of prey consumed on
      Choisya ternata, a species with smooth leaves. However, similarly few eggs were
      eaten on the smooth, but waxy leaved Euonymus japonicus as on Ceanothus
      thyrsiflorus, demonstrating that morphological characters of leaves other than
      the possession of hairs and trichomes may affect the rates of predation. The
      implications of these results for the tritrophic interactions between plant,
      predator and prey, and the development of suitable biological control strategies
      are discussed.

PMID- 11228590
TI  - Age structure of a population of Ixodes ricinus (Acari: Ixodidae) in relation to
      its seasonal questing.
AB  - Three sites in south west Scotland, each having one deciduous and one coniferous
      woodland with populations of roe deer, were sampled over three years for Ixodes
      ricinus Linnaeus ticks using cloth drags. Nymphs and adult ticks were age graded
      by dissection of gut and Malpighian tubules and staining for lipid with Sudan
      red. Temperature and relative humidity were recorded in developmental and
      questing microclimates. Two annual cohorts of both nymphs and adults were found.
      For both instars one cohort became apparent in early spring and the other in
      autumn. The timing of the cohorts of nymphs corresponded to peaks of numbers
      questing, but neither females nor males had any clear seasonal pattern of
      questing. The maximum life of questing nymphs and adults was three to four
      months. Nymphs and adults were found questing at all months of the year and at
      temperatures ranging from 3.5 degrees C to 29.3 degrees C. Questing of larvae in
      summer peaks of numbers was positively correlated with temperature and negatively
      correlated with relative humidity. These results are explained by a descriptive
      model which invokes behavioural and morphogenetic diapause. Tests of the model
      are discussed and it is proposed that the main adaptive advantage of the complex
      life cycle is to permit moulting and oviposition to occur at favourable summer
      temperatures in ticks that have engorged at any time of the year.

PMID- 11228592
TI  - Risk of upper gastrointestinal bleeding and perforation associated with low-dose
      aspirin as plain and enteric-coated formulations.
AB  - BACKGROUND: The use of low-dose aspirin has been reported to be associated with
      an increased risk of upper gastrointestinal complications (UGIC). The coating of
      aspirin has been proposed as an approach to reduce such a risk. To test this
      hypothesis, we carried out a population based case-control study. METHODS: We
      identified incident cases of UGIC (bleeding or perforation) aged 40 to 79 years
      between April 1993 to October 1998 registered in the General Practice Research
      Database. Controls were selected randomly from the source population. Adjusted
      estimates of relative risk (RR) associated with current use of aspirin as
      compared to non use were computed using unconditional logistic regression.
      RESULTS: We identified 2,105 cases of UGIC and selected 11,500 controls. Among
      them, 287 (13.6%) cases and 837 (7.3%) controls were exposed to aspirin,
      resulting in an adjusted RR of 2.0 (1.7-2.3). No clear dose-effect was found
      within the range of 75-300 mg. The RR associated with enteric-coated formulations
      (2.3, 1.6-3.2) was similar to the one of plain aspirin (1.9, 1.6-2.3), and no
      difference was observed depending on the site. The first two months of treatment
      was the period of greater risk (RR= 4.5, 2.9-7.1). The concomitant use of aspirin
      with high-dose NSAIDs greatly increased the risk of UGIC (13.3, 8.5-20.9) while
      no interaction was apparent with low-medium doses (2.2, 1.0-4.6). CONCLUSIONS:
      Low-dose aspirin increases by twofold the risk of UGIC in the general population
      and its coating does not modify the effect. Concomitant use of low-dose aspirin
      and NSAIDs at high doses put patients at a specially high risk of UGIC.

PMID- 11228591
TI  - The mouse anterior chamber angle and trabecular meshwork develop without cell
      death.
AB  - BACKGROUND: The iridocorneal angle forms in the mammalian eye from
      undifferentiated mesenchyme between the root of the iris and cornea. A major
      component is the trabecular meshwork, consisting of extracellular matrix
      organized into a network of beams, covered in trabecular endothelial cells.
      Between the beams, channels lead to Schlemm's canal for the drainage of aqueous
      humor from the eye into the blood stream. Abnormal development of the
      iridocorneal angle that interferes with ocular fluid drainage can lead to
      glaucoma in humans. Little is known about the precise mechanisms underlying angle
      development. There are two main hypotheses. The first proposes that morphogenesis
      involves mainly cell differentiation, matrix deposition and assembly of the
      originally continuous mesenchymal mass into beams, channels and Schlemm's canal.
      The second, based primarily on rat studies, proposes that cell death and
      macrophages play an important role in forming channels and beams. Mice provide a
      potentially useful model to understand the origin and development of angle
      structures and how defective development leads to glaucoma. Few studies have
      assessed the normal structure and development of the mouse angle. We used light
      and electron microscopy and a cell death assay to define the sequence of events
      underlying formation of the angle structures in mice. RESULTS: The mouse angle
      structures and developmental sequence are similar to those in humans. Cell death
      was not detectable during the period of trabecular channel and beam formation.
      CONCLUSIONS: These results support morphogenic mechanisms involving organization
      of cellular and extracellular matrix components without cell death or atrophy.

PMID- 11228593
TI  - [Efficacy of specific immunotherapy in children with bronchial asthma, sensitised
      to dermatophagoides pteronyssinus].
AB  - The aim of study was the evaluation of efficacy of specific immunotherapy using
      Alavac S HDM for 2-4 years in children with atopic bronchial asthma induced by
      Deramtophagoides pteronyssinus. The study was carried out in a group of 33
      children aged 5-18 years, from the Outpatient Department of Immunology at the
      National Research Institute of Mother and Child. The children demonstrated
      clinical symptoms of asthma and had a medical history typical for this disease.
      Diagnostic procedures including skin prick tests and estimation of specific IgE
      to Dermatophagoides pteronyssinus by Pharmacia-CAP system gave positive results.
      The efficacy of therapy was monitored by a clinical score of symptoms with 0-10
      20-30 points, recording symptoms relating to intensity of dyspneaa, wheezing,
      cough, value of PEF and concomitant medications for example corticoids and beta
      antagonists. In the study group, 31 children (94%) with asthma treated by
      specific immunotherapy (AlavacS HDM) improved. This was confirmed by a
      statistically significant difference. The results indicate that specific
      immunotherapy is effective in the treatment of asthma in children sesitized to
      Dermatophagoides pteronyssinus.

PMID- 11228594
TI  - [Sensitivity to cow's milk proteins and gluten in children's allergic disease].
AB  - Aim of the study was the evaluation of sensitivity to cow's milk and gluten
      participation in children's allergic disease. Our studies were carried out in a
      group of 191 children, aged between 7 months and 18 years, with sensitivity to
      cow's milk proteins and gluten in type I and/or IV according to Gell and Coombs.
      Sensitivity to these allergens was confirmed in 88.4% of the 216 examined
      children with allergic disease. We showed a prevalent frequency of allergen
      specific T-cell responses in mechanism IV (in type IV - 79.58%, in type I -
      10.99%, in I+IV - 9.42%). Evidence is presented that sensitivity to cow's milk
      proteins and gluten in I and IV Gell's and Coombs' mechanisms is more likely in
      small children and that it decreases with age.

PMID- 11228596
TI  - [Thyroiditis in children. Personal observations].
AB  - Enlargement of the thyroid gland, local tenderness and thyroid function disorder
      are common symptoms of thyroiditis. Hashimoto's thyroiditis (chronic lymphocytic
      thyroiditis) is the most common form of thyroiditis in children. This disease is
      a frequent cause of acquired hypothyroidism. Hashimoto's thyroiditis (HT) is
      characterised by infiltration of the thyroid gland by lymphocytes, gradual
      destruction of the gland and production of various thyroid autoantibodies, mainly
      antimicrosomal (ATM) and antithyroglobulin antibodies (ATGL). 54 children (45
      girls and 9 boys) aged from 11 to 18 with confirmed or suspected HT were
      observed. The clinical diagnosis of HT was confirmed by fine needle aspiration
      biopsy (FNAB) in 27 patients. In one case HT was histologicaly confirmed after
      thyroid surgery. FNAB was not carried out in 19 patients and in 7 cases FNAB was
      thyroiditis negative. All patients were positive for ATM and/or ATGL. Initially
      24 patients were euthyroid. Hypothyroidism was recognized in 8 children,
      subclinical hypothyroidism in 11 children. One patient was hyper- thyroid. 51
      patients were treated with l-thyroxin. Ultrasonography revealed variable thyroid
      abnormality in all patients: hyperplasia in 38 patients, multinodular goiter or
      solitary nodule in 15 patients. 8 children suffered from associated disease: 5
      patients from allergy, 1 patient from trombocytopenia, 1 from alopecia areata, 1
      from secondary amenorrhea. Follow up examination of children with HT must be
      continued due to the risk of hypothyroidism or neoplastic disease of thyroid.

PMID- 11228595
TI  - [Aneuploidy and histopathological classification, according to the
      Musculoskeletal Tumour Society and WHO, of osteosarcoma in children and
      adolescents].
AB  - A flow cytometry analysis in children and adolescents with osteosarcoma was
      carried out. Investigation concerned 32 fresh surgical specimens (from patients
      after preoperative chemotherapy) and 18 paraffin-embedded tumour tissues (archive
      material). The correlation of aneuploidy population parameters to malignancy
      grading acc. to WHO (GI-GIII) and MSC histopathological classification, was
      investigated. It was shown that all specimens with aneuploid populations
      correlated with the histophatological diagnosis of osteosarcoma. Thus cytometry
      analysis can be a useful and rapid complementary method to conventional
      histophtatological diagnosis. On the contrary, no correlation was found between
      the aneuploid parameters and the low grade and high-grade osteosarcoma acc. to
      WHO and MSC classification. The Multicycle computer system is useful in
      retrospective analysis of paraffin-embedded tumour tissues. It is suggested that
      for this kind of investigation fresh diagnostic specimens (before preoperative
      chemotherapy) would be more adequate.

PMID- 11228597
TI  - [Congenital defects in the newborn--difficulties in prenatal diagnosis].
AB  - The aim of this work is an analysis of developmental defects in newborn infants,
      born in the Clinical Department of Pregnancy Pathology and Reproduction in
      Zabrze, during the 19 months of its existence. Difficulties in prenatal diagnosis
      of developmental defects are presented and their structure is discussed. The
      study included 1524 live born infants with birth weight over 500 g and 12
      stillborn. In the live born group developmental defects were found in 71 (4.6%)
      infants. Among the 12 stillborn infants developmental defects were present in one
      child (8.3%). The most common developmental defects, in our material, were those
      of the skeletal system and heart defects. Prenatally, developmental defects were
      diagnosed in 8% of the examined foetuses. The quality of health care in pregnant
      mothers of the investigated newborn infants was assessed, with relation to
      medical examination, ultrasonographic scan and biochemical screening tests. In
      many cases, modern standards of management were not maintained.

PMID- 11228598
TI  - [Use of oxygen therapy during labour and acid-base status in the newborn].
AB  - The effect of supplemental maternal oxygen therapy on acid-base status has for
      years been a subject of controversies. There is still no general agreement about
      oxygen administration in pregnancy or in labour. Many clinicians believe that in
      normal pregnancy maternal oxygen treatment has merely negligible, if any,
      influence on the foetus. Maternal oxygen therapy has frequently been suggested
      when oxygen supply to the foetus was insufficient, viz. in antepartum or
      intrapartum hypoxia. The aim of this study was to determine whether a brief
      maternal hyperoxygenation during caesarean section or during the second stage of
      normal delivery affects cord blood acid-base status measured at birth. Patients
      with uneventful term pregnancy admitted to the delivery room in spontaneous
      labour or indicated for elective caesarean section were matched and prospectively
      ascribed to the control or treatment group. The latter received 60% oxygen for
      ca. 10 min at 15 L/min by a face mask. We studied 41 normal term infants of
      healthy mothers (24 from caesarean sections, the remaining 17 delivered
      vaginally). The control group consisted of normal newborns chosen according to
      the same criteria except that their mothers had no oxygen supplementation.
      Immediately after delivery, umbilical cord paired blood samples were drawn.
      Arterial and venous specimens were analysed for blood gases and acid-base balance
      parameters. Statistical analysis assisted by computer software was performed
      using Mann-Whitney U test. A p value < 0.05 was considered significant. All
      tested parameters related to the acid-base status and blood gases were similar in
      the treatment and control groups. Concluding, a short period of maternal
      hyperoxygenation either in the second stage of vaginal spontaneous delivery or
      during caesarean section did not affect umbilical cord blood acid-base status
      measured at birth.

PMID- 11228599
TI  - [Selected methods of supporting early interactions between parents and their
      hospitalised newborn child].
AB  - The quality of social interactions in early childhood is an important factor in
      mental development. Hospitalisation of the child in the neonatal period
      jeopardises these early contacts between parents and their child. The author
      briefly describes selected methods of supporting parent-child interactions in the
      neonatal department or neonatal intensive care unit environment.

PMID- 11228600
TI  - [Current views on requirements for vitamin D, calcium and phosphorus,
      particularly in formula fed infants].
AB  - Calcium (Ca) and phosphorus (P) absorption depends on vitamin D. Vitamin
      deficiency in children results in rickets and osteoporosis in adults. Prematurely
      born infants are at risk of osteopenia and rickets. Skin synthesis of vitamin D
      can obtain the level of 10 000 IU (250 ug) when the whole body is exposed to the
      sun. Recent opinion on vitamin D requirement establishes the level of more than
      80 nmol/L of 25(OH)D. There are no recommendations for children but it seems that
      due to the risk of skin cancer, exposure to the sun in children will be limited
      and as a result higher dose of vitamin D will be needed. Calcium and phosphorus
      are the most common minerals of the human body. Calcium concentration in human
      milk is not related to the intake. Calcium intake of calcium in premature infants
      is 70-140 mg/100 kcal. Phosphorus content in breast milk, even as low as 15 mg%,
      can maintain the optimal Ca/P ratio of 2/1. Prolonged breast feeding without
      additional Ca and P, may result in reduced bone mineralisation. Higher content of
      calcium in infant formula in comparison to human milk is due to the fact that Ca
      absorption from breast milk is 60% in comparison to 40% absorption from the
      formula.

PMID- 11228601
TI  - [Multiresistant bacterial strains in infections of children treated at the
      National Research Institute of Mother and Child in 1999].
AB  - The aim of the study was the evaluation of multiresistant strains in infections
      of children treated at the National Research Institute of Mother and Child
      (NRIMC). During 1999, 23145 inoculations and 3873 antibiotic susceptibility tests
      were done. 2711 multiresistant strains were detected of which 59.2% were Gram
      negative rods and 40.8% - Gram-positive cocci. The Gram-negative rods were tested
      for production of beta-lactamases (ESBL), resistance to aminoglicosides, imipenem
      and piperacillin/tazobactam. Gram-positive cocci were tested for methicilin and
      aminoglicosides resistance. Cross-resistance between macrolides, lincosamides and
      streptogramines was also investigated. Significant participation of
      multiresistant bacterial strains, mainly Gram-negative, in infections among
      patients treated in intensive care units of the Institute should be stressed.

PMID- 11228602
TI  - [Epidemiological situation of tuberculosis in children and youth of Poland].
AB  - After the Second World War tuberculosis was a very serious health problem in
      Poland. Tuberculosis in children and youth constituted an important part of the
      morbidity in the whole population. In 1957 almost 27% of newly detected cases
      concerned children (19.9%) and adolescents (7%). This percentage decreased
      systematically through 15.1% in 1965 to 3,0% of total morbidity in 1999 (0.8% in
      children aged 0-14 and 2.2% in youth aged 15-19 years). Improvement was also
      observed in the general tuberculosis morbidity rate. The number of new cases
      diagnosed in 1965 was 57511 (morbidity rate per 100000 population was 182.6) and
      in 1990 the number of new cases diagnosed was 16136 (morbidity rate 42.3 per
      100000 population). In 1999 - 12179 new cases in the whole population were
      registered (morbidity rate 31.5 per 100000 population). The decrease of morbidity
      in children and adolescents was more rapid than in adults (mean value 8.9%). The
      number of new tuberculosis cases diagnosed in 1965 in the age group 0-14 was
      4248, (43.5 per 100000 population) and fell to 108 new cases in 1999 (1.4 per
      100000 population). In the 15-19 years age group in 1965 - 3621 new cases were
      diagnosed (125.2 per 100000 population) and in 1999 - 265 new cases (8 per 100000
      population) were detected. The most common form of tuberculosis in children and
      in youth as well as in adults is pulmonary tuberculosis.

PMID- 11228603
TI  - [Congenital hypothyroidism].
AB  - Congenital hypothyroidism is one of the most common diseases in paediatric
      endocrinology. Thyroid hormones are essential in brain development, which takes
      place during foetal life and early postnatal life up to the 2nd year of age. The
      main etiologic factors of congenital hypothyroidism are anomalies of development,
      function and regulation of the thyroid gland. Clinical signs of thyroid hormone
      deficiency in infants are non-specific. Early diagnosis is based on newborn
      screening for congenital hypothyroidism, which was started in Poland in 1977.
      Treatment within the first days of life with appropriate dosage of thyroxine
      prevents mental retardation. This paper summarises current knowledge on
      congenital hypothyroidism in children.

PMID- 11228604
TI  - [A model for clinical diagnosis-treatment of the newborn with an abnormal
      screening test for hypothyroidism and in children with congenital
      hypothyroidism].
AB  - Congenital hypothyroidism occurs in 1:4000 newborns. Mass screening for
      congenital hypothyroidism constitutes a major progress in the prevention of
      mental retardation. The neonatal screening programme in Poland was established
      and implemented by the National Research Institute of Mother and Child from the
      middle of the 70. and reorganised in 1997. Recall examinations in the infants,
      substitute therapy with l-thyroxine and the follow-up of hypothyroid infants and
      children are presented.

PMID- 11228606
TI  - [Neuronal bases of visual perception].

PMID- 11228607
TI  - [Phacofragmentation with chopper and spatula].

PMID- 11228608
TI  - [Correlation between diabetic retinopathy and microalbuminuria].

PMID- 11228610
TI  - Chemical and thermal injuries of the eyes. Surgical and medical treatment based
      on clinical and pathophysiological findings.
AB  - Light burns heal well within a few days. Severe chemical and thermal injuries of
      the eyes destroy surface epithelia and cause ischemic necroses of conjunctiva,
      cornea, sclera, iris, ciliary body, and lids. An inflammatory response follows
      with leucocyte infiltration and release of inflammatory mediators.
      Prostaglandins, lipoxygenase products, cytokines, superoxide radicals and
      Iysosomal enzymes are known to be active in eye burn disease. Their activities
      result in corneal, scleral and conjunctival ulceration, tissue proliferation and
      scarification, which develop within weeks, months and even years after the
      accident. Pathophysiological events produce defined clinical pictures. Some
      agents take special actions, e.g. alkali penetrates within seconds into the
      anterior chamber, sulfuric acid burns as well as quick lime burns forming slaked
      lime produce considerable heat. Hydrofluoric acid is highly toxic and induces
      early necroses. Heat causes deep ischemic necroses and lateron strongly shrinking
      scars. Onset and intensity of first aid decided on the outcome. Immediate rinsing
      is essential. Cool water, saline, Ringers lactate solution and BSS are good
      rinsing media. For first aid, buffered Previn seems suitable. Major chemical and
      thermal injuries need a variety of medical and surgical treatments: Necroses must
      be excised surgically. Tenon plasty is performed to reconstruct conjunctiva.
      Amnion-, limbus- and early keratoplasty or artificial epithelium are applied,
      initially to save the cornea from melting, and later to restore vision.
      Conjunctical, lid and intraocular surgery may be necessary. The aim of medical
      treatment is to suppress the inflammatory response and to prevent infection.
      Corticosteroids, antibiotics, ascorbate and inhibitors of proteolytic enzymes are
      used. Secondary glaucoma must not be forgotten. Extensive therapy is sometimes
      rewarding, results are presented.

PMID- 11228611
TI  - [Ultrastructural changes of the retinal pigment epithelium in pigs fed with a fat
      rich diet].
AB  - PURPOSE: To determine if the intake of a rich diet is related to ultraestructural
      changes and with an increase in lipofuscin accumulation in porcine retinal
      pigment epithelium (RPE). METHODS: The animals were divided into two groups of 6
      pigs each. In the first group (control), a restricted diet of chow mix was
      supplied. The second group (fat-fed group) was fed with the same type of
      nutritional diet, however one third of the food was replaced by saturated fatty
      acid. Total cholesterol, HDL, LDL, and triglycerides were determined at the
      beginning and at the end of the experiment. After 12 weeks, the eyes were
      enucleated and the RPE structure was examined by electron microscopy. RESULTS: No
      significant differences were observed in the RPE lipofuscin accumulation between
      the control group and the fat-fed group (p=0.3). However, morphological disorders
      such as nuclear pyknosis, accumulation of electron dense particles in Bruch's
      membrane, and the accumulation of empty and lipid-like vacuoles in the cytoplasm
      were observed in the RPE of the fat-fed group but not in the control animals.
      CONCLUSIONS: The ultrastructural changes observed in the porcine RPE can be
      related to a high fat diet to the increase in lipid plasma levels.

PMID- 11228612
TI  - [The hollowness of the optic nerve].

PMID- 11228618
TI  - Federal funding for automated external defibrillators in rural areas is proposed.

PMID- 11228619
TI  - Executive order may secure patients' rights while bill remains stalled in
      Congress.

PMID- 11228620
TI  - After a year, stents pose no more risks for women than men.

PMID- 11228621
TI  - Advocates of medical treatment, surgery, and percutaneous coronary intervention
      agree on one thing.

PMID- 11228622
TI  - African-Americans are less likely to receive life-saving care when faced with
      heart disease.

PMID- 11228623
TI  - Entry inhibitor combination shows promise.

PMID- 11228625
TI  - Index of suspicion. Case #2. Diagnosis: Biliary atresia.

PMID- 11228624
TI  - Hypothyroidism from HAART.

PMID- 11228626
TI  - GeneMedix sets sight on Southeast Asia.

PMID- 11228627
TI  - Truth and consequences.

PMID- 11228628
TI  - Truth and consequences.

PMID- 11228629
TI  - FP provision in GUM clinics.

PMID- 11228630
TI  - The Nova T series of IUDs.

PMID- 11228631
TI  - Edward VII's appendix.

PMID- 11228632
TI  - Living wills.

PMID- 11228633
TI  - A simple method of shaving avulsed scalp before replantation.

PMID- 11228634
TI  - Lipoma of the abdomen after suction lipectomy.

PMID- 11228635
TI  - Angiographic TRAM flap delay.

PMID- 11228637
TI  - Universal ailments.

PMID- 11228636
TI  - Endoscopic harvest of the gracilis muscle.

PMID- 11228638
TI  - Sugars pave the road to destruction.

PMID- 11228640
TI  - Improving the success of homeopathy 2: Developing and demonstrating
      effectiveness. Proceedings of an international conference. 15-16 April 1999,
      London, United Kingdom.

PMID- 11228641
TI  - Congenital disorders of glycosylation IIa cause growth retardation, mental
      retardation, and facial dysmorphism.

PMID- 11228642
TI  - Older surgeons' records for endarterectomy worse than those of younger surgeons.

PMID- 11228643
TI  - Proceedings of the Asia-Pacific Consensus Meeting for the Diagnosis and Treatment
      of Hepatitis B and C. Kyoto, Japan, 6-7 September 1999.

PMID- 11228644
TI  - Proteomics Forum '99. Proceedings of a meeting of the German Electrophoresis
      Society. Munich, Germany, October 25-27, 1999.

PMID- 11228645
TI  - Regarding Blasko et al. palladium-103 brachytherapy for prostate carcinoma.
      IJROBP 2000;46:839-850.

PMID- 11228646
TI  - More sex education requested.

PMID- 11228647
TI  - 3rd International Symposium on NeuroVirology. 14-16 September 2000. San
      Francisco, California, USA. Proceedings and abstracts.

PMID- 11228648
TI  - Stress fracture of the sacrum in a child.

PMID- 11228649
TI  - Proceedings of the National Institutes of Health Statistical Genetics Initiative
      Symposium: New Qualitative Methods to Map Genes for Complex Traits. Half Moon
      Bay, California, USA. October 24-25, 1999.

PMID- 11228650
TI  - Steroids and endometrial breakthrough bleeding. Proceedings of a meeting.
      Melbourne, Australia, 4-5 May 1999.

PMID- 11228651
TI  - Congenital esotropia.

PMID- 11228652
TI  - Research in medical education. Proceedings of the 39th annual conference.
      Chicago, Illinois, USA. October 30-November 1, 2000.

PMID- 11228653
TI  - Myths and Medicare.

PMID- 11228654
TI  - MAM2000. Molecular Approaches to Malaria. Proceedings of a meeting. Lorne,
      Victoria, Australia. 2-5 February 2000.

PMID- 11228655
TI  - Women's Health and the Environment: The Next Century--Advances in Uterine
      Leiomyoma Research. Conference proceedings. 7-8 October 1999, Research Triangle
      Park, North Carolina, USA.

PMID- 11228656
TI  - IPPC '99. Proceedings of the 1st Pacific Rim 2-DE Meeting. Tokyo, Japan, August
      29-September 1, 1999.

PMID- 11228657
TI  - A journey from gamete to newborn. Proceedings of an international meeting.
      Leuven, Belgium, September 20-23, 2000.

PMID- 11228658
TI  - American College of Radiology ACR Appropriateness Criteria 2000.

PMID- 11228659
TI  - Cellular peptidases in immune functions and diseases 2. Proceedings of an
      international conference. September 12-14, 1999, Magdeburg-Herrenkrug, Germany.

PMID- 11228660
TI  - Paediatric intensive care transfers: 1.

PMID- 11228661
TI  - GP core business.

PMID- 11228662
TI  - Errors in emergency medicine conference. May 25, 2000. Proceedings.

PMID- 11228663
TI  - [On article by Gekht AB, Avakian GN, Gusev EI "Modern standards of diagnosis and
      treatment of epilepsy in Europe"].

PMID- 11228664
TI  - Future employment of allopathic medical graduates.

PMID- 11228665
TI  - Oxidative pathways in health and disease conference and the 8th meeting of the
      Society for Free Radical Research (Australasia). 1-4 December 1999, Sydney.

PMID- 11228666
TI  - [Proceedings of the 2nd Sanofi-Synthelabo Cardiology Forum. Ischemic cardiopathy
      and hypertensive cardiopathy: convergence and divergence. Cernobbio, 23-24 June
      2000].

PMID- 11228668
TI  - Society for Social Medicine annual meeting 2000. Abstracts.

PMID- 11228667
TI  - [All-Polish Symposium. Reproductive Immunology. Lodz, 19-20 September 1999].

PMID- 11228669
TI  - Grand mal in hypotension.

PMID- 11228671
TI  - International Association of Endocrine Surgeons--manuscripts presented during
      International Surgical Week. Vienna, August 15-20, 1999.

PMID- 11228672
TI  - Medical Ethics at the Dawn of the 21st Century. January 5-8, 1998, Jerusalem,
      Israel.

PMID- 11228673
TI  - HCFA ups payments to nursing homes but delays major PPS refinements.

PMID- 11228674
TI  - Drug for irritable bowel syndrome taken off the market.

PMID- 11228675
TI  - Your career guide. Landing the job you want. Acing the interview.

PMID- 11228676
TI  - Proceedings of the XVth International Conference on the Social Sciences and
      Medicine: Societies and Health in Transition. Eindhoven, The Netherlands, 16-20
      October 2000.

PMID- 11228678
TI  - Proceedings of the 18th Southern Biomedical Engineering Conference and the 2nd
      International Conference on Ethical Issues in Biomedical Engineering. Clemson,
      South Carolina, USA. May 21-23, 1999.

PMID- 11228677
TI  - Thermodynamics and the structure of biological macromolecules. A special issue in
      honour of Henryk Eisenberg.

PMID- 11228679
TI  - Identifying core obstetric and gynecologic skills required of, and used by,
      graduates of the Faculty of Medicine and Health Sciences, United Arab Emirates
      University.
AB  - BACKGROUND: Acquisition of core practical skills by students assures quality and
      relevance of medical education. PURPOSE: To determine whether students and
      interns are acquiring core obstetric and gynecologic skills. METHODS: A self
      administered questionnaire was sent to obstetric and gynecology clerkship
      coordinators (n = 3), consultants (n = 14), residents (n = 13); interns (n = 13)
      and final-year students (n = 29; n = 93, response rate = 77%, N = 72). The
      questionnaire contained a stimulus list of 21 clinical, 8 communication, and 5
      professional skills. RESULTS: Of 34 listed skills, 24 were identified as core
      skills. At least 50% of consultants, faculty, and residents expected 28 core
      skills to be covered in the undergraduate program. At least 50% of interns
      believed that 21 core skills had been acquired at graduation. CONCLUSION: Our
      curriculum is facilitating acquisition of core obstetric and gynecologic skills.

PMID- 11228680
TI  - Can a brief clinical practicum influence physicians' communications with patients
      about alcohol and drug problems? Results of a long-term follow-up.
AB  - BACKGROUND: A survey was conducted in 1996 to assess the perceptions of medical
      school graduates concerning alcohol and drug problems among their patients, and
      their attitudes and comfort toward addressing these issues. Survey questionnaires
      were sent to all individuals who graduated from Wright State University School of
      Medicine, Dayton, Ohio, between 1982 and 1990. PURPOSE: The study aimed to assess
      the long-term impact that participation in a brief clinical experience in tandem
      with a standard didactic substance abuse curriculum material had on former
      medical students now in practice. The study examined how these physicians
      perceived their skills in communicating with their patients about alcohol and
      drug use, and attendant problems. METHODS: An Alcohol and Drug Use Communication
      (ADUC) scale was developed by combining several survey items. Data analyses
      included correlation assessments of the ADUC scale and other variables, and
      multiple-regression analyses for identifying factors independently associated
      with the ADUC scale although other factors were controlled. RESULTS: Former
      students who participated in the brief clinical program, known as the Weekend
      Intervention Program, as part of their medical school curriculum were more likely
      to report having better communication concerning alcohol and drug use with their
      patients than students who only had didactic education. Also, additional training
      in addictions after graduation was significantly associated with better alcohol
      and drug use communication between physician and patient. Former students who
      participated in the Weekend Intervention Program were more than twice as likely
      as those without the experience to report confronting at least 10% of their
      patients about their concerns about the patients' alcohol or drug use.
      CONCLUSIONS: The results of this study suggest that undergraduate medical
      students' participation in a modest clinical program can enhance substance abuse
      education. Through increased training in substance abuse, physicians reported
      greater confidence in their ability to relate to patients with substance abuse
      problems.

PMID- 11228681
TI  - The audition elective and its relation to success in the National Resident
      Matching Program.
AB  - BACKGROUND: Many medical students take audition electives in an effort to improve
      their chances of being selected by a residency program. PURPOSE: The study was to
      determine if audition electives improved student success in the National Resident
      Matching Program. METHOD: A questionnaire was mailed to graduates of the
      University of South Dakota School of Medicine from 1977 (the charter graduating
      class) through 1997. Comparisons were done between students who took audition
      electives and those who did not. Statistical analysis was performed by chi-square
      or Fisher Exact tests for smaller groups. RESULTS: The data show no statistically
      significant difference in first-choice matching for the total group (p = .35),
      primary care (p = .44), or nonprimary care subgroups (p = .38). Sample size is
      inadequate for sufficient analysis of individual specialties. CONCLUSIONS: The
      limited time available to provide students with a broad education and the
      disadvantages of taking audition electives should be considered when advising
      students about 4th-year schedules.

PMID- 11228682
TI  - Response rate comparisons of e-mail- and mail-distributed student evaluations.
AB  - BACKGROUND: The proliferation of electronic information delivery systems has led
      to increasing use of e-mail as a rapid method of gathering information. Little
      research has been conducted on the use of e-mail for collecting curriculum
      evaluations. PURPOSE: To compare e-mailed and mailed educational evaluations for
      4th-year medical students. METHODS: Curriculum evaluations were sent to 4th-year
      medical students who were randomly assigned to receive the survey either by mail
      or e-mail. RESULTS: Mailed evaluations yielded a higher return rate, fewer number
      of students omitting items, and shorter responses to an open-ended question than
      evaluations completed via e-mail. CONCLUSIONS: Although the findings have limited
      generalizability because of low response rates and small sample sizes, the
      results suggest caution when using e-mail to collect curriculum evaluations from
      4th-year medical students.

PMID- 11228683
TI  - Information and informatics literacy: skills, timing, and estimates of
      competence.
AB  - BACKGROUND: Computing and biomedical informatics technologies are providing
      almost instantaneous access to vast amounts of possibly relevant information.
      Although students are entering medical school with increasingly sophisticated
      basic technological skills, medical educators must determine what curricular
      enhancements are needed to prepare learners for the world of electronic
      information. PURPOSE: The purpose was to examine opinions of academic affairs and
      informatics administrators, curriculum deans and recently matriculated medical
      students about prematriculation competence and medical education learning
      expectations. METHODS: Two surveys were administered: an Information Literacy
      Survey for curriculum/informatics deans and a Computing Skills Survey for
      entering medical students. RESULTS: Results highlight differences of opinion
      about entering competencies. They also indicate that medical school
      administrators believe that most basic information skills fall within the domain
      of undergraduate medical education. CONCLUSIONS: Further investigations are
      needed to determine precise entry-level skills and whether information literacy
      will increase as a result of rising levels of technical competence.

PMID- 11228684
TI  - Clinicians and computers: friends or foes?
AB  - BACKGROUND: Computer-aided learning is accepted by students as a learning
      resource, but the views of the teaching community are largely unknown. PURPOSE:
      To document clinicians' experience with computers and to record their attitudes
      toward computer usage in clinical practice and student education. METHODS:
      Questionnaire mailed out to all clinicians, including interns and residents,
      fellows, and attending physicians in 3 major teaching hospitals in South
      Australia, with a total of 646 clinical staff. RESULTS: Replies were received
      from 246 staff. Eighty percent of clinicians had at least 2 years of experience
      with computers and used computers for at least 2 hr each week. Despite this,
      there was an obvious lack of conviction among clinicians that computer-aided
      learning was of use in student education and assessment. This may reflect their
      lack of experience with this medium as an educational tool. CONCLUSIONS: If
      computer-aided learning is to make any significant impact on medical student
      education, it must be carefully and objectively evaluated, and its benefit must
      be clearly demonstrated to clinical teachers.

PMID- 11228685
TI  - MedEthEx Online: a computer-based learning program in medical ethics and
      communication skills.
AB  - BACKGROUND: Bioethics education often focuses on lectures and discussions to set
      a foundation for ethical decision making. Our goal was to bridge the gap between
      classroom learning and bedside competence through computer-assisted instruction.
      This article assesses the efficacy of MedEthEx Online, a computer-based learning
      program as part of a required Bioethics course. DESCRIPTION: Of 173 American
      medical students, 89 in Section 1 attended 8 bioethics lectures and 8 small-group
      discussions. Eighty-four in Section 2 had a similar course, although two group
      discussions were replaced with computerized learning. We compared (a) final exam
      scores, (b) topic-specific question scores, (c) performance with standardized
      patients, (d) self-assessments, and (e) course evaluations. EVALUATION: Exam
      scores were comparable, although computerized-learning students scored higher in
      specific exam areas, felt somewhat more clinically prepared, and rated the course
      slightly better. Standardized patient interactions differed, although they were
      comparable overall. CONCLUSION: MedEthEx Online is a viable option for fostering
      effective communication and problem resolution skills.

PMID- 11228686
TI  - Husbandry and husbandry-related diseases of ornamental fish.
AB  - With the continued popularity of fish as pets, a market can be established for
      veterinarians with experience with aquatic animals. Fish owners often form a
      strong and significant emotional, as well as economic, bond with their aquariums
      or ponds. With proper husbandry, common mistakes made by fish owners can be
      treated, if not avoided. Diagnosis and treatment of a majority of common fish
      problems can be facilitated through an understanding of proper saltwater and
      freshwater fish husbandry.

PMID- 11228687
TI  - Psittacine nutrition.
AB  - Nutrition is defined as it relates to deficiencies, toxicities, and physiological
      states in birds. Levels of some nutrient requirements are given along with signs
      of deficiency. Signs of toxicity and the levels of nutrients required to produce
      them are discussed for energy, calcium, and protein. Behavioral aspects of
      nutrition in weaning, obesity, and dietary changes are characterized. The role of
      nutrition in diseases such as infection, hemochromatosis, achromatosis, gout,
      liver disease, and kidney disease are discussed.

PMID- 11228688
TI  - Husbandry and nutrition of hedgehogs.
AB  - Hedgehogs are becoming increasingly popular as pets. This article provides a
      broad overview of those factors with which practitioners must be familiar to
      provide guidance to hedgehog owners. The taxonomy, anatomy, and natural history
      of the common pet species are presented along with commonly observed behaviors.
      Information on the reproduction and neonatal management is described. Current
      recommendations for handling, housing, and feeding these animals are also
      discussed.

PMID- 11228689
TI  - Feeding recommendations for the house rabbit.
AB  - The feeding recommendations for the pet or house rabbit include grass hay fed ad
      libitum, dark leafy green vegetables fed at one cup per 5 pounds of body weight,
      and a maximum of 1 cup of high fiber pellets per 5 pounds of body weight. These
      recommendations are based on the feeding behavior, anatomy, and gastrointestinal
      physiology of the rabbit. Feeding this diet reduces the occurrence of common
      gastrointestinal tract disease in the house rabbit. This article reviews the
      feeding behavior, anatomy, and gastrointestinal physiology of the rabbit.

PMID- 11228690
TI  - Nutrition of rodents.
AB  - Access to a diet that provides adequate nutrition is one of the most important
      environmental factors influencing the well-being of rodent colonies. The dietary
      ingredient and nutrient composition, as well as the potential biological and
      chemical contaminant concentrations, are factors for consideration in selecting
      diets for a specific rodent colony. Estimated nutrient requirements have been
      published for the rodent species that are commonly used in biomedical research.
      The nutrient concentrations in adequate diets for other captive rodent species
      that are not used in biomedical research are more difficult to obtain. However,
      reasonable estimates of their nutrient requirements can be obtained by
      extrapolation of data from rodent species of a similar metabolic weight and size
      or from nutrient concentrations of diets that have a history of acceptable
      performance in the species of interest. Captive rodent colonies should be
      provided with nutritionally balanced diets with only limited amounts of succulent
      foodstuffs. The practice of feeding rodent colonies specific cereal grains is
      discouraged, since no single grain provides a balanced rodent diet.

PMID- 11228691
TI  - Ferret nutrition.
AB  - The unusually short intestinal tract of ferrets and closely related mustelids
      lacks a cecum and ileocolic valve. As a result, the transit time of ingesta in
      these carnivores is very rapid compared with other animals, and their food is
      inefficiently digested. Although the precise nutritional requirements of ferrets
      have not been determined by feeding defined diets, information has been compiled
      from experience feeding commercial and analyzed homemade diets to breeding
      ferrets, fitch, and mink at all stages of their lives. The requirements of spayed
      or neutered pet ferrets are met by allowing them constant access to drinking
      water and a palatable, pelleted, or extruded, 90% dry matter, premium cat or
      ferret food that, as fed, contains at least 15% fat and 30% high quality, meat
      source protein, less than 30% carbohydrates, and approximately 4 Kcal of
      metabolizable energy per gram. Lower density diets with more carbohydrate and
      less protein are associated with poor reproductive performance and growth and
      greater susceptibility to infectious and metabolic diseases.

PMID- 11228692
TI  - Nutrition of ornamental fish.
AB  - Because thousands of species comprise the aquarium hobby, ornamental fish
      nutrition is an art and a science that must be approached systematically and
      holistically. Examinations of species-specific anatomy and natural history are
      useful starting points. Food fish research provides fundamental nutritional
      information, but food fish are not ideal models for all ornamentals. This article
      briefly addresses freshwater and marine fish issues, including considerations for
      pond fish and live foods.

PMID- 11228693
TI  - Potbellied pig husbandry and nutrition.
AB  - Vietnamese potbellied pigs, when appropriately cared for, make excellent pets for
      some people. However, their proper housing, care, and training is more
      challenging to the average person than that required for most traditional pets,
      such as dogs and cats. Failure to feed and house the pet pig appropriately
      results in the most common health and behavior problems. The obese, intractable
      pet pig gives little pleasure to a pet owner and appears to lead a very poor
      quality life, frequently leading to the pet pig being given away or worse.
      Preventing health and behavior problems is easy if pet owners are armed with
      correct information early, either before or immediately after their acquisition
      of a pet pig. A veterinarian prepared to share this information can save the
      lives of many pigs as well as keep clients happy and coming back.

PMID- 11228694
TI  - Nutrition and husbandry of callitrichids (marmosets and tamarins).
AB  - Proper care of callitrichids (marmosets and tamarins) requires a thorough
      understanding of the natural history, nutritional requirements, and husbandry
      requirements of these small delicate monkeys. This article provides information
      to formulate appropriate diets, to bottle-feed a rejected infant, to learn normal
      behaviors, to give an overview of nutritionally related diseases and treatments,
      provide information about husbandry, and to provide an overview of infectious
      diseases. Veterinarians will be better able to assist callitrichid owners in
      their proper care with the information provided in this article.

PMID- 11228695
TI  - Designing environments for captive amphibians and reptiles.
AB  - Environments for captive amphibians and reptiles play a critical role in their
      long-term health, and veterinarians need to be informed of the requirements of
      various species when evaluating the causes of disease. Enclosure size,
      substrates, landscaping, heating, lighting, and relative humidity are the areas
      of primary concern when designing vivaria. Two different approaches are used when
      keeping amphibians and reptiles, depending primarily on the size of the species
      maintained: a laboratory animal-type system and naturalistic vivarium system. The
      latter places more emphasis on simulating essential elements of natural habitats
      and on aesthetic appeal of the display.

PMID- 11228696
TI  - Nutrition of captive reptiles.
AB  - In reptile practice, most nutritional problems arise from improper husbandry,
      including poor feeding management and provision of imbalanced diets. Each reptile
      species has its own requirements for temperature and humidity, space and social
      interaction, lighting, and habitat components. Failure, to provide these
      requirements often results in failure to thrive and secondary nutritional
      disorders. Common dietary problems include deficiencies of energy, calcium,
      vitamin D3, vitamin A, and fiber.

PMID- 11228698
TI  - Analytical chemistry and the law.

PMID- 11228697
TI  - Reproductive management of captive parrots.
AB  - Studies of the behavior of Amazon parrots throughout a reproductive trial
      indicate that activities such as food gathering, which may occupy large fractions
      of the activity budget of wild parrots, occupy little time in captivity. This may
      be one factor contributing to the large percentage of time during which Amazon
      parrots are generally inactive in typical captive conditions. The extent of
      inactivity in captive Amazons creates an open time niche wherein enrichment
      devices might play a role in improving their well being. Studies of the
      reproductive endocrinology and the behavior of parrots suggest that hand rearing
      may impair adult fertility and nest box use. Hand rearing may also cause adult
      Cockatiels to lay eggs on cage floors rather than in nest boxes. However, the use
      of nest boxes with oversized nest entrances can be very effective in alleviating
      chronic floor laying in Cockatiels. Another egg-laying problem in Cockatiels,
      unwanted egg laying, can be prevented by the use of long-acting formulations of
      the superactive GnRH agonist, leuprolide acetate, which presumably [figure: see
      text] acts in birds, as in mammals, by down-regulating pituitary GnRH receptors.
      Manipulations to limit the increases in prolactin normally seen during incubation
      in poultry can significantly increase egg production. As clutch size in
      Cockatiels may also be limited by rising prolactin levels, such manipulations may
      be effective in stimulating egg production in parrots. An alternative approach
      for increasing flock egg production is to place foster eggs in nests of Cockatiel
      pairs that are slow to lay. This technique stimulates males to increase their
      nest-oriented behavior and, subsequently, may stimulate egg laying in some
      females that might not otherwise have laid eggs. The parental phases of
      reproduction in Amazon parrots are often a time of heightened aggressiveness
      towards humans, but low levels of serum testosterone in males during that time
      suggest that this particular interspecies aggressiveness may not be dependent on
      elevated testosterone levels. Occasional human handling during the nestling stage
      may produce a degree of tameness comparable with hand-reared chicks, yet not
      impair adult reproductive performance. Such handling may also alter the immune
      status of captive parrots, and possibly reduce the serum corticosterone response
      to handling. If so, occasional human handling during the nestling stage could
      improve the adaptation of parrots to captivity.

PMID- 11228699
TI  - Analytical chemistry and the law: progress for half a millennium.
AB  - Chemistry has been used for the detection of adulteration since the earliest
      times of recorded history going back at least 3 1/2 millennia. Since the
      invention of printing the subject is easier to follow. Aspects of law and its
      application via chemistry in regard to precious metals, food, drink and medicinal
      materials are reviewed over the last half millennium with particular reference to
      the U.K.

PMID- 11228700
TI  - The position of the analyst as expert: yesterday and today.
AB  - The interrelation between law and analytical chemistry 150 years ago is outlined,
      showing that similar problems to today already existed at that time. Examples of
      present-day cases of judicial investigations are given and consequences for the
      duty of the analytical chemist are discussed.

PMID- 11228701
TI  - Historical development of expertise in forensic chemical analysis. General
      survey, illustrated by case studies from the Viennese Institute.
AB  - The history of forensic chemical analysis shows a development from the mere
      quotation of a concentration value to an expert opinion which helps to explain
      manifold circumstances of the case under consideration. The development of
      forensic expertises on chemical problems connected to forensic medicine reveals
      two essential stages: 1. A period, when sensual perceptions were the only means
      of investigation and 2. a period, when developments in chromatographic separation
      and spectrometric identification have permitted objectified results.

PMID- 11228702
TI  - Proving beyond all reasonable doubt--analytical aspects.
AB  - An overview is presented of the problems and challenges facing the analyst who is
      asked to provide data to support the law. Factors that the analyst should
      consider include: the legal reasons for performing the analysis; situations where
      analytical data should and should not be used in support of litigation; the
      scientific basis for the legislation; and the sample source and method of
      sampling.

PMID- 11228703
TI  - Fact finding beyond all reasonable doubt--legal aspects.
AB  - A description is provided of the European (esp. German and Austrian) legal
      concept of "fact finding beyond all reasonable doubt". The uncontested principle
      of the free evaluation of evidence is closely connected with the dispute about
      the "probative standard" (= this means the degree of the judge's conviction which
      is necessary for the fact finding). There can neither be a purely subjective nor
      a purely objective theory of the probative standard. Because of the human limits
      of possible perception and of the subjective cognitive faculties the total
      conviction of truth as demanded by the "conviction-of-truth-theory" could never
      mean absolute certainty. It is sufficient if "no other reasonable man with a
      clear view of the conditions of life would be convinced". On the other hand, the
      objective theory, which sees the judge's task only in consideration of
      probabilities, becomes more and more important. As a third principle, there is
      the preponderance principle influenced by the Anglo-American system.

PMID- 11228704
TI  - Aggravation of licensing procedures by doubtful thermodynamic data.
AB  - Environmental prognosis by geochemical modelling is a scientific approach to
      several open questions of general public interest. Two prominent fields where
      geochemical modelling holds an important share are the remediation of
      contaminated former uranium mining areas and safety assessment of radioactive
      waste repositories in the geosphere. In both fields, application of geochemical
      modelling is stipulated by public authorities. The enormous complexity of models
      that can be handled by computers rises the awareness on the meaningfulness of a
      modelling result and demands for provision of an estimate of the dependability of
      a calculation output by the computers. It is obvious that bias, over- and
      underestimation of uncertainty in input data reduces the relevance of the
      calculation output. Chemistry contributes important data to geochemical
      modelling, both from field analysis and in the fundamental physico-chemical
      quantities enclosed into the thermodynamic data base. Some examples will be given
      where progress in quality assessment of chemical data may further the predictive
      power of geochemical modelling.

PMID- 11228705
TI  - "Demonstration" vs. "designation" of measurement competence: the need to link
      accreditation to metrology.
AB  - Formal acceptance of the results of chemical laboratories is increasingly
      organized through a) accreditation of measuring laboratories nationally and b)
      mutual recognition of accreditation internationally (through formal Multilateral
      Recognition Agreements, MRAs). However, real comparability of results of
      measurements is realized by using common (internationally agreed) measurement
      scales which make these results traceable to this scale, i.e. "traceable" to the
      same (internationally agreed) value of the unit of that scale. In addition, the
      criterion against which the evaluation is done, should be "external" to the
      measurement laboratories which are being evaluated. This is realized in IRMM's
      International Measurement Evaluation Programme (IMEP) where evaluation is
      performed against values which are anchored using "metrology", the science of
      measurement with its own rules, which offers a sound foundation for measurement
      in all scientific disciplines. It is argued in this paper that the demonstration
      of measurement capability against values on such scales provides a result
      oriented rather than a procedure-oriented evaluation. Thus, competence can be
      "demonstrated" rather than just "designated" and this can be shown to both
      customers and regulators. It inspires more confidence.

PMID- 11228706
TI  - Comparability of thermodynamic data--a metrological point of view.
AB  - In order to compare and to interpret chemical measurements, compliance with
      general rules of metrology is compulsory. Such rules are the more important the
      more the chemical measurements are applied under circumstances where material
      assets and goods or immaterial values like health may be affected. Metrology of
      chemical measurements attempts to define rules for achieving comparability and
      for guaranteeing quality of analytical data. Thermodynamic data are commonly
      derived from a set of analytical measurements. Comparability among thermodynamic
      data is an important issue especially for those data to be applied in politically
      sensitive issues of environmental prognosis, long-term safety assessment of
      nuclear waste repositories in deep geological formations and assessment of
      environmental impact of technical intervention in the geosphere. Taking the data
      evaluation step in the traceability chain of thermodynamic data as an example,
      the existing thermodynamic data is shown to be affected by deficiencies in
      comparability and quality that may severely limit its dependability in
      environmental prognosis. The need for a metrologically acceptable approach is
      demonstrated. Statistical concepts improving a reliable assignment of meaningful
      measurement uncertainty to a thermodynamic datum are presented. Unresolved
      issues, i.e. measurement uncertainty of a pH measurement, hampering the
      construction of a traceability chain are outlined.

PMID- 11228707
TI  - Inverse vs. classical calibration for small data sets.
AB  - In classical calibration, the statistically uncertain variable y is regressed on
      the error-free variable x for a number of known samples, and the results are used
      to estimate the x value (x0) for an unknown sample from its measured y value
      (y0). It has long been known that inverse calibration--regression of x on y for
      the same data--is more efficient in its prediction of x0 from y0 than the
      seemingly more appropriate classical procedure, over large ranges of the
      controlled variable x. In the present work, theoretical expressions and Monte
      Carlo calculations are used to illustrate that the comparison favors the inverse
      procedure even more for small calibration data sets than for the large sets that
      have been emphasized in previous studies.

PMID- 11228708
TI  - Estimation of the uncertainty of CRMs in accordance with GUM: application to the
      certification of four enzyme CRMs.
AB  - Uncertainties of four enzyme-CRMs that have recently been certified in a co
      operation between the IRMM and the International Federation for Clinical
      Chemistry were estimated. Estimation was based on the sum of the uncertainties of
      characterization, homogeneity and stability. Data from the certification
      collaborative study were used to estimate laboratory uncertainties, which form
      the basis for the uncertainty of characterization. Estimations for the
      uncertainty of homogeneity were derived from classical homogeneity studies. The
      estimations of uncertainty of stability caused the most difficulties. Realistic
      uncertainties fitting the needs of customers while being derived from measurement
      data based on theoretical considerations were obtained.

PMID- 11228709
TI  - Simultaneous spectrophotometric determination of La, Ho, Mn 5-Br-PADAP complexes
      using multivariate calibration with partial least-squares (PLS) data evaluation.
AB  - A simple and fast analytical pocedure is proposed for the simultaneous
      spectrophotometric determination of lanthanum, holmium and manganese in synthetic
      ceramics, (La(0.8-x) Hox Sr0.2 MnO3), by using the partial least-squares (PLS)
      method. As chromogenic agent 5-Br-PADAP [2-(5-bromo-2-pyridylazo)-5
      diethylaminophenol] was used, which form colored complexes with the three
      elements studied. To avoid metal hydrolysis, a mixture of ethanol and Triton X
      100 at pH 9.5 was used for all experiments. A set of 17 calibration solutions
      measured throughout the 400-700 nm wavelength range was used in the calibration
      step. The concentration range for Mn(II) was 1-12 x 10(-6) mol L-1, while the
      range for the rare earth elements La(III) and Ho(III) was 2-8 x 10(-6) mol L-1.
      In order to demonstrate the applicability of the proposed method, a set of
      artificial samples containing the three analytes in variable proportions was
      prepared and analyzed. The analytical results obtained were quite acceptable with
      relative errors not greater than 7% in most cases.

PMID- 11228711
TI  - X-ray fluorescence analysis of trace metal ions following a preconcentration of
      metal-diethyldithiocarbamate complexes by homogeneous liquid-liquid extraction.
AB  - A homogeneous liquid-liquid extraction method for 36 metal ions with
      diethyldithiocarbamate was studied. As a result, 11 metal ions were extracted as
      metal-chelates. Under the experimental conditions, the maximum concentration
      factor was 500 (i.e., 0.1 mL of sedimented liquid phase was produced from 50 mL
      of aqueous phase). Moreover, the proposed method was utilized as a
      preconcentration method for X-ray fluorescence analysis of these metals. The
      recovery of each metal was ca. 97-100%. All calibration curves were linear over
      the range of 5.0 x 10(-7) mol L-1 to 1.0 x 10(-5) mol L-1. The detection limits
      were at the 10(-8) mol L-1 levels and the relative standard deviations were below
      5% (5 determinations). When the proposed method was used for the determination of
      contaminants in a synthetic sample (Al-based alloy model) and of components in an
      Au-Pd alloy, the results were satisfactory.

PMID- 11228710
TI  - Strategy for water analysis using ICP-MS.
AB  - The developed strategy permits determination in three steps of sixty-seven
      elements using inductively coupled plasma mass spectrometry (ICP-MS). Sodium, Mg,
      Si, S, Cl, K, and Ca are determined in a first step; B, Al, P, Cr, Fe, Mn, Ni,
      Cu, Zn, As, Se, Ag, Cd, Sb, Ba, Hg, and Pb are determined in a second step; and
      Li, Be, Ti, V, Co, Ga, Ge, Br, Rb, Sr, Y, Zr, Nb, Mo, Sn, Te, I, Cs, La, Ce, Pr,
      Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Hf, Ta, W, Pt, Au, Tl, Bi, Th, and U
      are analyzed in a third step. The figures of merit obtained are adequate to carry
      out water quality monitoring and other hydrochemical studies, such those based in
      the application of hydrochemical fingerprinting to water management.

PMID- 11228712
TI  - Development of a voltammetric method for the determination of iron(III) in Zn-Fe
      alloy galvanic baths.
AB  - A square wave voltammetric method with a static mercury drop electrode (SMDE) was
      developed for the quantitative determination of iron (III) in Zn-Fe alloy
      galvanic baths. Real alloy bath samples were analyzed by the standard addition
      method and recovery tests were carried out. 0.50 mol L-1 sodium citrate (pH 6.0)
      or 0.20 mol L-1 oxalic acid (pH 4.0) were applied as supporting electrolytes
      resulting in both cases in a peak potential of about -0.20 V vs. AgIAgCl
      (saturated KCl). The iron (III) concentration in the alloy bath was 9.0 x 10(-4)
      mol L-1. A good correlation (r = 0.9999) was achieved between the iron (III)
      concentration and the peak current in the electrolytes studied, with linear
      response ranges from 1.0 x 10(-6) to 1.2 x 10(-4) mol L-1. Interference levels
      for some metals such as copper (II), lead (II), chromium (III) and manganese (II)
      that can hinder the Zn-Fe alloy deposition were evaluated; only copper (II)
      interferes seriously.

PMID- 11228714
TI  - Rapid liquid chromatographic determination of residual penicillin G in milk.
AB  - A simple and rapid high-performance liquid chromatographic (HPLC) method for
      determination of residual penicillin G (benzylpenicillin, PCG) in milk was
      developed. The sample preparation was performed by stirring with ethanol and
      reacting with 5 M 1,2,4-triazole-mercury (II) chloride solution at 65 degrees C
      for 10 min followed by an ultra centrifugation step. The HPLC separation was
      carried out using a Mightysil RP-4GP column, a mobile phase of acetonitrile and
      0.1 M phosphate buffer (pH 6.5) (35:65, v/v) and a photo-diode array detector.
      The average recoveries from spiked PCG (0.004, 0.01, 0.05 and 0.1 microgram/mL)
      were above 86% with coefficients of variation between 1.2 and 4.5%. The limit of
      detection was 0.004 microgram/mL. This value corresponds to the maximum residue
      limit (MRL) in milk (0.004 microgram/mL, EU and Japan). The total time required
      for the analysis of one sample was below 40 min.

PMID- 11228713
TI  - Determination of organophosphorus insecticides in natural waters using SPE-disks
      and SPME followed by GC/FTD and GC/MS.
AB  - Two methods for the analysis of ten organophosphorus insecticides in natural
      waters using solid phase extraction disks containing C18 and SDB and solid phase
      microextraction fibers containing polyacrylate (PA) are developed. Bromophos
      ethyl, bromophos methyl, dichlofenthion, ethion, fenamiphos, fenitrothion,
      fenthion, malathion, parathion ethyl and parathion methyl were determined by
      GC/MS and GC/FTD. The SPE-disks require only 1000 mL of sample and provide a
      method limit of detection in the range of 0.01-0.07 microgram/L and recovery
      rates from 60.7 to 104.1%. The solid phase microextraction (SPME) technique
      requires 2-5 mL of water sample and provides a method limit of detection in the
      range of 0.01 to 0.05 microgram/L for all detectors and the recoveries compared
      to distilled water ranged from 86.2 to 119.7%. The proposed methods were applied
      to the trace level screening determination of insecticides in river water samples
      originating from different Greek regions.

PMID- 11228715
TI  - ETAAS method for the determination of Cd, Cr, Cu, Mn and Se in blood fractions
      and whole blood.
AB  - An electrothermal atomic absorption method (ETAAS) for the direct determination
      of trace elements (Cd, Cr, Cu, Mn, Se) both in blood fractions (erythrocytes,
      plasma and lymphocytes) and whole blood was developed. Zeeman background
      correction and graphite tubes with L'vov platforms were used. Samples were
      diluted with HNO3/Triton X-100 and pipetted directly into the graphite tube.
      Ashing, pretreatment and atomization steps were optimized carefully for the
      different fractions and elements applying different matrix modifiers for each
      element. For the lymphocyte fraction a multi-fold injection technique was
      applied. Low detection limits of the ETAAS method (Cd 0.13 microgram/L, Cr 0.11
      microgram/L, Cu 0.52 microgram/L, Mn 0.13 microgram/L, Se 0.7 microgram/L of
      whole blood) combined with small quantities of sample necessary for analysis
      allow determination of trace elements in this matrix. Verification of possible
      differences in the trace element status of humans was performed with statistical
      significance (P < 0.05). In addition, a contribution to the determination of
      normal values of essential elements was achieved. The method was applied for
      determination of trace elements in human blood and blood fractions of two groups
      (n = 50) different in health status.

PMID- 11228716
TI  - Microwave assisted extraction for trace element analysis of plant materials by
      ICP-AES.
AB  - Application of microwave assisted extraction for the decomposition and
      dissolution of plant samples for trace metal determination by ICP-AES was
      examined. Dried onion, leaves of spinach beet and three reference materials CTA
      OTL-1, CTA-VTL-2 and CL-1 were analyzed. Water, EDTA and hydrochloric acid (0.01,
      0.10 and 1.0 M, respectively) were used as leaching solutions. The extraction
      efficiency was investigated by comparison of the results with those obtained
      after microwave wet digestion. HCl was found to be very suitable for quantitative
      extraction of B, Ba, Cd, Cu, Mn, Ni, Pb, Sr and Zn from the samples. For
      reference materials, the measured concentrations are well consistent with the
      certified values. The use of EDTA led to a complete extraction of B, Cd, Ni, Pb,
      Sr and Zn. Water was found to be a good leaching solution for boron. For
      extraction with HCl and EDTA, the RSD values for the concentrations measured were
      below 8% for most of the elements.

PMID- 11228717
TI  - Study of the adsorption behavior of heavy metal ions on nanometer-size titanium
      dioxide with ICP-AES.
AB  - A new method using nanoparticle TiO2 as solid-phase extractant coupled with ICP
      AES was proposed for simultaneous determination of trace elements. The adsorption
      behavior of nanometer TiO2 towards Cu, Cr, Mn and Ni was investigated by ICP-AES,
      and the adsorption pH curves, adsorption isotherms and adsorption capacities were
      obtained. It was found that the adsorption rates of the metal ions studied were
      more than 90% in pH 8.0-9.0, and 2.0 mol L-1 HCl was sufficient for complete
      elution. Nanometer TiO2 possesses a significant capacity for the sorption of the
      metal ions studied which is higher than the capacity of silica, the commonly used
      extractant. The method has been applied to the analysis of some environmental
      samples with satisfactory results.

PMID- 11228718
TI  - Critical care monitoring.
AB  - Critical care monitoring in exotic practice is limited by the small size and the
      physiologic diversity of many patients. However, many of the principles applied
      to humans and other mammals can be extrapolated to monitoring in exotic animals.
      Advances in the monitoring of human patients offer the potential for more
      practical, low-cost monitoring in critical exotic patients in the future.

PMID- 11228719
TI  - Critical care of pet birds. Procedures, therapeutics, and patient support.
AB  - Critically ill birds must be recognized, accurately assessed, and provided rapid
      appropriate treatment. This article presents a method of assessment and
      supportive care for critically ill birds. A problem-oriented approach based on
      clinical signs is presented, accompanied by suggested diagnostic tests.
      Techniques used to treat critically ill birds are also discussed.

PMID- 11228720
TI  - Urgent care of the pet rabbit.
AB  - Emergency and critical care principles are similar for all mammals; however, the
      physiology and natural behavior of rabbits create an animal that is easily
      stressed and requires specialized handling techniques. This article reviews
      diagnostic and therapeutic techniques, nutritional support, and pain management
      for urgent care of pet rabbits. Common differential diagnoses for emergencies are
      briefly reviewed by the clinical presentation. A table of drug dosages used for
      urgent care is provided.

PMID- 11228721
TI  - Small mammal critical care.
AB  - In emergency situations, veterinarians often are presented with critical patients
      of any species. The principles for critical care in traditional species such as
      the dog or cat can be applied to other small mammals. Although there are many
      unique aspects of the anatomy and physiology of different species, emergency care
      of small mammals can be instituted with the adaptation of products found in many
      general practices. Careful assessment of the patient, prioritization of the
      injuries, and rapid intervention can be life saving in any species.

PMID- 11228722
TI  - Emergency care for potbellied pigs.
AB  - Because of the limited number of veterinarians treating potbellied pigs, many pet
      pigs do not receive proper preventative health care. The potbellied pig's
      continued popularity among urban dwellers ensures that veterinarians who treat
      small and exotic animals will be contacted by owners of pet pigs with real or
      perceived emergencies. Regardless of their knowledge of swine, the information
      contained in this article should enable any veterinarian to provide basic
      emergency care for pet pigs.

PMID- 11228723
TI  - Emergency care of reptiles.
AB  - Common reptile emergencies are reviewed in this article and the fundamentals of
      emergency care are provided. Important points include obtaining a complete
      history and husbandry review, physical examination, diagnostic tests, fluid
      support, anesthetics, and antibiotics.

PMID- 11228724
TI  - Amphibian emergency and critical care.
AB  - Amphibians present unique challenges for the clinician in the diagnosis and
      treatment of life-threatening conditions. Their adaptability to both aquatic and
      terrestrial lifestyles leaves them vulnerable to dehydration and fluid overload,
      either of which may accompany serious disease. This article presents the most
      common emergency conditions in amphibians, the physiologic basis of disease, and
      a guide to the diagnosis and treatment of amphibian emergencies.

PMID- 11228725
TI  - Emergency and critical care of fish.
AB  - The keeping of fish as pets is a hobby that has experienced increasing popularity
      over the past decade. The hobby has also become more sophisticated in recent
      years and a growing number of veterinarians are gaining clinical experience and
      knowledge in the area of pet fish medicine. The opportunity to apply this
      knowledge to a pet fish problem can be a rewarding experience. This article
      focuses on managing acute and critical problems of pet fish at times when
      veterinary intervention is required within an emergency time frame.

PMID- 11228726
TI  - Emergency care of invertebrates.
AB  - Invertebrates are of increasing importance to the veterinary profession, but
      little scientifically-based information exists on their emergency care.
      Therefore, basic principles--supportive care, including administration of fluids,
      and specific therapy (where available)--must be followed up on. Knowledge and
      understanding of the biology and natural history of these animals are essential
      if critical care is to prove successful.

PMID- 11228727
TI  - Emergency avian surgery.
AB  - Avian surgery is an exercise of preparedness; this statement is never so true as
      in emergency and critical care situations. The techniques used in avian surgery
      are significantly different from those used in larger species and require
      microsurgical techniques. Before initiating a surgical procedure, the patient
      must be evaluated and, in many cases, prepared or preconditioned. Rarely is
      surgery such an emergency that the prognosis would not be improved by readying
      the patient. Techniques of tissue handling, approaches to the coelomic cavities
      and a select number of surgical procedures are described.

PMID- 11228728
TI  - Management of avian flock emergencies.
AB  - Managing avian flock emergencies requires a thorough history, physical
      examination, and record review before instituting appropriate therapy. Although
      the general thought processes are similar between approaching a sick individual
      bird and a "diseased" aviary, the actual steps are different. Infectious diseases
      are often a component of aviary emergencies but are rarely the primary cause of
      flock "disease." Managing flock emergencies typically goes beyond addressing
      individual pathogens. Recognizing, evaluating, and treating flock emergencies are
      discussed with the intent to provide a better understanding of flock health
      medicine principles.

PMID- 11228729
TI  - Emergency care of raptors.
AB  - Emergency care of raptors often requires extensive diagnostics and therapeutic
      regimens to stabilize and support the ill or injured raptor. Whether falconry
      birds, educational birds, or raptors from the wild are presented, various medical
      conditions must be addressed to help guide the practitioner toward a complete
      recovery for the raptor.

PMID- 11228730
TI  - Emergency and critical care of ferrets.
AB  - Gastrointestinal disease, neoplasia, cardiac disease, and endocrinopathy are
      among the most common syndromes affecting the ferret that presents in an
      emergency situation. Knowledge of these and other disease processes, indicated
      diagnostic testing, and immediate treatment protocols are critical to provide
      efficient and effective care to the ferret in crisis.

PMID- 11228731
TI  - Clinical examination of fish in private collections.
AB  - The rapid advancement of fish medicine over the past 10 years has led to a
      drastically improved ability to manage the individual pet fish successfully.
      Principle physiologic differences between fish and higher vertebrates include the
      lack of ability to regulate body temperature (this has a profound effect on the
      immune system), the use of gills for respiration, and the importance of
      osmoregulation in the aquatic environment. Components of the clinical history for
      a fish patient should include information on the environment, tank mates, recent
      medical history, and specific information on the affected individual. Fish can be
      manually restrained or safely anesthetized with methane tricaine sulfonate,
      depending on their size, condition, and circumstances. Diagnostic techniques
      useful for fish patients include gill, skin, and fin biopsy; hematology;
      cytology; radiology; and ultrasound. Preventive medicine programs should include
      water quality, nutritional management, sanitation, and quarantine.

PMID- 11228732
TI  - Basic husbandry and clinical assessment of the amphibian patient.
AB  - The veterinarian presented with an amphibian patient must be prepared to assess
      both the animal's medical condition and its husbandry record; good health is
      inextricably linked to proper care and diet. This article provides the clinician
      with guidelines for maintaining amphibians in captivity, including information on
      climate control and lighting, housing and cage enrichment, and nutrition. The
      article also covers questions to ask when taking a history, methods of restraint,
      and practical advice on the equipment and techniques used to conduct a complete
      physical examination of the amphibian patient.

PMID- 11228733
TI  - Clinical evaluation of reptiles.
AB  - A detailed history and physical examination usually provides the veterinarian
      with a list of possible differential diagnoses and indicates which further
      investigations may be necessary to make a definitive diagnosis. Radiography,
      ultrasonography, endoscopy, hematology, blood biochemistry, and microbiological
      and parasitologic investigations are all proven techniques that are used
      extensively in reptile medicine. A logical case workup enables the clinician to
      make a previously elusive reptile diagnosis and offers this interesting group of
      animals veterinary services comparable with that already expected for more
      domesticated pets.

PMID- 11228734
TI  - Examination and preventive medicine protocols in psittacines.
AB  - Preventive medicine is the best insurance for effective avian health maintenance
      and infectious disease control. Psittacine birds should have a yearly physical
      examination including a thorough history. Additionally, these animals require
      adequate management and husbandry including a commercial bird food diet
      supplemented with fresh fruits and vegetables. A complete preventive medicine
      program should include diagnostic tests as deemed necessary by the avian
      veterinarian in addition to strict quarantine, vaccination, and disinfection.
      Necropsy and histopathology are also important components of an effective
      preventive medicine program.

PMID- 11228735
TI  - Physical examination of passerines.
AB  - A physical examination of a passerine incorporates the same basic techniques used
      for other avian species. Although frequently a concern for practitioners, the
      small size of many of these patients can be overcome with a few technical and
      equipment modifications. When evaluating clinical findings and collecting
      diagnostic samples, veterinarians must remain cognizant of important anatomical
      differences between passerines and psittacines so that they can interpret the
      results of these tests properly. Because of the many species contained within
      this order, practitioners should gather as much useful information as possible
      when examining a novel species. In this way, we will continue to expand the
      medical knowledge base for this large and diverse group of birds.

PMID- 11228736
TI  - Clinical assessment of gallinaceous birds and waterfowl in backyard flocks.
AB  - Obtaining a complete history and performing a physical examination are key steps
      in any clinical assessment. In addition, being familiar with common clinical
      signs helps in the formulation of a differential diagnosis. Once a definitive
      diagnosis is made, it is important to follow up each case with client education
      as well as the development of preventive medicine programs for avian patients.

PMID- 11228737
TI  - Physical examination and preventive care of rabbits.
AB  - As rabbits gain increasing popularity as house pets, more rabbit owners are
      seeking basic preventive veterinary care. Although a knowledge of the unique
      anatomic and physiologic characteristics of pet rabbits is essential, annual
      examination and review of diet and husbandry are as important as with any other
      species. Many disease states can be detected or prevented with routine veterinary
      care. Despite all the advances in diagnostic testing in veterinary medicine,
      there will never be a substitute for a complete physical examination.

PMID- 11228738
TI  - Clinical evaluation of rodents.
AB  - The clinical examination of small rodents is like that of more conventional pets
      in that the same systematic approach is used to arrive at a problem list. The
      difference with these species is that their diminutive size, high metabolic rate,
      and lack of patience may be problematic for the clinician. With continued
      practice and patience, veterinarians can begin to feel comfortable in adding
      small rodents to the growing components of their practices.

PMID- 11228739
TI  - Clinical examination of chinchillas, hedgehogs, prairie dogs, and sugar gliders.
AB  - Veterinarians in small animal practice are being presented with an ever
      increasing number of exotic species. It has become critical that veterinarians
      expand their professional knowledge to include the basic procedures necessary for
      the proper diagnosis and therapy of these animals. Yet the husbandry,
      temperaments, physiology, and anatomy of many of these species make extrapolation
      from our well-developed techniques in dog and cat medicine inadequate. This
      article discusses some of the major species concerns and clinical findings of
      chinchillas, hedgehogs, prairie dogs, and sugar gliders presented to the
      veterinary practitioner. Practical techniques for evaluation of these animals
      with minimal stress (to the animal, the practitioner, and the client) and maximum
      efficiency are addressed.

PMID- 11228740
TI  - Ferrets. Examination and preventive medicine.
AB  - As ferrets are anatomically and physiologically similar to dogs and cats, the
      basic elements of ferret examination, disease processes, and preventive health
      are familiar to small-animal practitioners. Like other domestic carnivores,
      ferrets are tolerant of handling and medical procedures, especially compared with
      rabbits, rodents, and most nondomestic mammals. These characteristics make
      ferrets amenable to many of the highly specialized diagnostic and therapeutic
      techniques that are now available in small-animal practice. Veterinarians who
      wish to add ferrets to their practices should be familiar with the ferret
      literature, but they should not forget to draw from the wealth of knowledge in
      canine and feline medicine when managing unusual or difficult ferret cases.

PMID- 11228741
TI  - Preventive health care for pet potbellied pigs.
AB  - Many small and exotic animal practitioners decline to see potbellied pigs,
      possibly because of their challenging behavior and the perception that in order
      to treat them, one must be very knowledgeable about swine medicine. With some
      basic information about their unique behavior and their preventive health care
      needs, however, seeing potbellied pigs in practice is easy and provides a much
      needed service in many communities. The behavior of the pig, recommended methods
      of restraint, physical examination, vaccinations, and parasite control are all
      discussed.

PMID- 11228742
TI  - Activation of NF-kappa B by reactive oxygen intermediates in the nervous system.
AB  - Nuclear factor kappa B (NF-kappa B) is a transcription factor crucially involved
      in glial and neuronal function. NF-kappa B is ubiquitously distributed within the
      nervous system, and its inducible activity can be discerned from constitutive
      activity. Prototypic inducible NF-kappa B in the nervous system is composed of
      the DNA-binding subunits p50 and p65 complexed with an inhibitory I kappa B-alpha
      molecule. A number of signals from the cell surface can lead to rapid activation
      of NK-kappa B, thus releasing the inhibition by I kappa B. This activates
      translocation of NF-kappa B to the nucleus, where it binds to kappa B motifs of
      target genes and activates transcription. Previous findings have identified
      reactive oxygen intermediates (ROI) as a common denominator of NF-kappa B
      activating signals. More specifically, hydrogen peroxide (H2O2) might be used as
      second messenger in the NF-kappa B system, despite its cytotoxicity. Analysis of
      pathways leading to NF-kappa B activation in the nervous system has identified a
      number of ROI-dependent pathways such as cytokine- and neurotrophin-mediated
      activation, glutamatergic signal transduction, and various diseases with crucial
      ROI involvement (e.g., Alzheimer's disease, Parkinson's disease, experimental
      autoimmune encephalomyelitis, multiple sclerosis, amyotrophic lateral sclerosis,
      and injury). A number of NF-kappa B-specific target genes contribute to the
      production of ROI or are involved in detoxification of ROIs. In this review,
      possible mechanisms and regulatory pathways of ROI-mediated NF-kappa B activation
      are discussed.

PMID- 11228743
TI  - In situ imaging of intracellular calcium with ischemia in lung subpleural
      microvascular endothelial cells.
AB  - We propose that generation of reactive oxygen species (ROS) during ischemia is
      associated with an increase in intracellular calcium ([Ca2+]i) in pulmonary
      capillary endothelial cells. We used an isolated rat lung model and
      epifluorescence microscopy to evaluate [Ca2+]i in subpleural microvascular
      endothelial cells in situ by ratio imaging of the fluorophores, Calcium Green and
      Fura Red (CG/FR). Lungs were ventilated continuously under control (continuously
      perfused) or global ischemia (no perfusion) and thus remained adequately
      oxygenated even with ischemia. Ischemia for 5 min led to increase in CG/FR,
      indicating increase in [Ca2+]i in endothelial cells in situ; CG/FR remained
      elevated during a subsequent 10 min of ischemia. Ca(2+)-free perfusion and
      gadolinium (100 microM) inhibited the increase in [Ca2+]i, while thapsigargin
      (250 nM) had no effect. These results indicate that increase in endothelial cell
      [Ca2+]i with ischemia was due to influx from the extracellular medium. Perfusion
      with N-acetyl-L-cysteine (20 mM) or diphenyleneiodonium chloride (10 microM)
      prevented the ischemia-mediated [Ca2+]i increase, suggesting a role for ROS in
      the Ca2+ changes with ischemia. Membrane depolarization by perfusion with high
      potassium (K+) or glyburide also resulted in increased [Ca2+]i whereas the K(+)
      channel agonist cromakalim, inhibited ischemia-mediated Ca2+ influx. We conclude
      that increased ROS generation with 'oxygenated' lung ischemia is associated with
      influx of Ca2+ and an increase in endothelial cell cytosolic calcium
      concentration.

PMID- 11228744
TI  - Redox control of Epstein-Barr virus replication by human thioredoxin/ATL-derived
      factor: differential regulation of lytic and latent infection.
AB  - Human thioredoxin (hTRX)/adult T-cell leukemia (ATL)-derived factor (ADF) was
      originally reported as an interleukin-2 (IL-2) receptor-alpha-inducing factor
      produced by human T-cell lymphotropic virus-1-positive (HTLV-1+) cell lines.
      Growing evidence indicates that hTRX/ADF plays important roles in cellular
      responses against oxidative stress and is involved in a variety of cellular
      functions. A high level of hTRX/ADF expression is also observed in other human
      virus-infected cell lines including those of Epstein-Barr virus (EBV) and human
      papillomavirus. In this report, we analyzed the effect of hTRX/ADF on lytic
      amplification and persistent replication of EBV as a model for lytic versus
      latent phase of viral replication in host cells. Addition of hTRX/ADF clearly
      suppressed lytic replication of EBV in Raji cells and B95-8 cells induced to the
      lytic phase of 12-O-tetradecanoylphorbol-13-acetate (TPA), and it prevented the
      death of these cells evoked by the lytic induction. In contrast, hTRX/ADF did not
      have any effect on persistent replication in the latent phase. These data
      indicated that hTRX/ADF prevents EBV-transformed cells from proceeding into the
      lytic phase and regulates cohabitation of EBV and its host cells.

PMID- 11228745
TI  - Arachidonic acid metabolites mediate angiotensin II-induced NADH/NADPH oxidase
      activity and hypertrophy in vascular smooth muscle cells.
AB  - Previously, we showed that angiotensin II stimulation of the NADH/NADPH oxidase
      is involved in hypertrophy of cultured vascular smooth muscle cells (VSMC). Here,
      we examine the pathways leading to oxidase activation, and demonstrate that
      arachidonic acid metabolites mediate hypertrophy by activating the p22phox-based
      NADH/NADPH oxidase. Angiotensin II stimulates phospholipase A2, releasing
      arachidonic acid, which stimulates oxidase activity in vitro. When arachidonic
      acid metabolism is blocked with 5,8,11,14-eicosatetraynoic acid (ETYA) or
      nordihydroguaiaretic acid (NDGA), oxidase activity decreases by 80 +/- 10%. In
      VSMC transfected with antisense p22phox to attenuate NADH/NADPH oxidase
      expression, arachidonic acid is unable to stimulate NADH/NADPH-dependent
      superoxide production. In these cells, or in cells in which NADH/NADPH oxidase
      activity is inhibited by diphenylene iodonium, angiotensin II-induced [3H]leucine
      incorporation is also inhibited. Attenuation of oxidase activation by inhibiting
      arachidonic acid metabolism with ETYA, NDGA, baicalein, or SKF-525A also inhibits
      angiotensin II-stimulated protein synthesis (74 +/- 2% and 34 +/- 1%,
      respectively). Thus, endogenous noncyclooxygenase arachidonic acid metabolites
      mediate angiotensin II-stimulated protein synthesis in cultured VSMC by
      activating the NADH/NADPH oxidase, providing mechanistic evidence for redox
      control of VSMC hypertrophy.

PMID- 11228747
TI  - Phospholipase D activation in endothelial cells is redox sensitive.
AB  - Reactive oxygen species (ROS) are implicated in the pathophysiology of a number
      of vascular disorders, including atherosclerosis. Recent studies indicate that
      ROS modulate signal transduction in mammalian cells. Previously, we have shown
      that ROS (hydrogen peroxide, fatty acid hydroperoxide, diperoxovanadate, and 4
      hydroxynonenal) enhance protein tyrosine phosphorylation and activate
      phospholipase D (PLD) in bovine pulmonary artery endothelial cells (BPAECs). In
      the present study, our aim was to investigate the role of exogenous thiol agents
      on ROS-induced PLD activation in conjunction with the role of cellular thiols-
      glutathione (GSH) and protein thiols--on PLD activation and protein tyrosine
      phosphorylation. Pretreatment of BPAECs with N-acetyl-L-cysteine (NAC) or 2
      mercaptopropionylglycine (MPG) blocked ROS-induced changes in intracellular GSH
      and PLD activation. Also, pretreatment with NAC attenuated diperoxovanadate
      induced protein tyrosine phosphorylation. Pretreatment of BPAECs with diamide or
      L-buthionine-(S,R)-sulfoximine (BSO), agents that lower intracellular GSH and
      thiols, enhanced PLD activity. Furthermore, NAC blocked diamide- or BSO-mediated
      changes in GSH levels, PLD activity, and protein tyrosine phosphorylation. NAC
      also attenuated diamide-induced tyrosine phosphorylation of proteins between 69
      and 118 KDa. These results support the hypothesis that modulation of thiol-redox
      status (cellular nonprotein and protein thiols) may contribute to the regulation
      of ROS-induced protein tyrosine phosphorylation and PLD activation in vascular
      endothelium.

PMID- 11228746
TI  - Antioxidants differentially regulate activation of nuclear factor-kappa B,
      activator protein-1, c-jun amino-terminal kinases, and apoptosis induced by tumor
      necrosis factor: evidence that JNK and NF-kappa B activation are not linked to
      apoptosis.
AB  - Tumor necrosis factor (TNF) is known to mediate its signaling through generation
      of reactive oxygen species (ROS), but the type of TNF signal regulated by ROS and
      the nature of the ROS species involved are not fully understood. In this report,
      we investigated the effect of various superoxide radical quenchers--pyrrolidine
      dithiocarbamate (PDTC), N-acetyl-L-cysteine (NAC), and glutathione (GSH)--an
      hydroxyl radical quencher (mannitol), and lipid peroxide quenchers--butylated
      hydroxytoluene (BHT) and butylated hydroxyanisole (BHA)--on TNF-induced
      activation of nuclear transcription factors-kappa B (NF-kappa B) and activator
      protein-1 (AP-1), c-jun amino-terminal kinase (JNK), and apoptosis in human
      monocytic U937 cells. TNF-induced NF-kappa B activation was inhibited by both
      superoxide and lipid peroxide quenchers but potentiated by an hydroxyl radical
      quencher. In contrast, none of the radical quenchers had any significant effect
      on TNF-induced AP-1 activation. TNF-induced JNK activation, similar to NF-kappa
      B, was inhibited by both superoxide and lipid peroxide quenchers but potentiated
      by hydroxyl radical quencher. TNF-induced activation of caspase activity was
      blocked by all three types of quenchers. TNF cytotoxicity, however, was
      potentiated by superoxide radical quenchers and suppressed by hydroxyl radical
      and lipid peroxide quenchers. Overall, these results suggest that hydroxyl
      radicals mediate TNF-induced apoptosis but not activation of NF-kappa B, AP-1,
      and JNK; superoxide radicals mediate NF-kappa B and JNK activation but potentiate
      apoptosis; and lipid peroxides are required for all the signals induced by TNF.

PMID- 11228748
TI  - Effect of hyperketonemia on blood monocytes in type-I diabetic patients and
      apoptosis in cultured U937 monocytes.
AB  - Recent studies have proposed a role for a reduced number of circulating monocytes
      in the development of atherosclerosis and circulatory diseases in diabetes.
      Ketosis is frequently encountered in type-I diabetics. This study was undertaken
      to test the hypothesis that hyperketonemia can lower blood monocyte count in type
      I diabetic patients. Blood monocyte count was significantly lower (p < 0.05) in
      diabetics (n = 27) compared with age-matched normal siblings (n = 22). Blood
      levels of acetoacetate (AA) and triglycerides were significantly higher in
      diabetics compared with normals. To examine whether hyperketonemia can directly
      alter the monocyte count in diabetics, we studied the effect of ketone bodies AA
      and beta-hydroxybutyrate (BHB) on U937 cells, a human-derived promonocytic cell
      line as an in vitro model. The cell culture studies showed a dose-dependent
      growth inhibition and induction of apoptosis as a result of treatment with AA in
      U937 cells. Furthermore, there was a significant decrease in GSH and increase in
      lipid peroxidation products in AA-treated U937 cells. Taken together, this study
      suggests that elevated levels of ketone body AA can result in oxidative damage,
      accelerated apoptosis, and inhibition of cell growth in monocytes, which in turn
      can lower monocyte count in the blood of type-I diabetic patients.

PMID- 11228750
TI  - Modulation of angiotensin II signaling for GATA4 activation by homocysteine.
AB  - Homocysteine (Hcy) is a redox active thiol-containing compound with pro-oxidant
      and pathogenic properties in the cardiovascular system. Angiotensin II (Ang II)
      also plays important roles in age-associated cardiovascular disease. Recently,
      the GATA4 transcription factor was recognized as a mediator of heart failure. We
      investigated the interrelationship of these elements in NIH/3T3 fibroblasts and
      found that Ang II induces GATA4 activity and Hcy alters Ang II signaling.
      Electrophoretic mobility shift assays determined that treatment of cells with Ang
      II induced DNA binding activity to the GATA consensus sequence. This activation
      was transient with a peak occurring at 30 min. Supershift analysis revealed the
      GATA binding protein as GATA4. Ang II also induced NFAT activity with similar
      kinetics. Pretreatment of cells with Hcy (100 microM) delayed the peak of Ang II
      induced NFAT and GATA activation to 60 min. Ang II-mediated activation of c-fos
      serum response factor (SRF) was similarly delayed by Hcy. These results suggest
      the pathogenic mechanism of Hcy action may be mediated in part via modulation of
      Ang II-signaling for gene transcription.

PMID- 11228749
TI  - Effects of the superoxide dismutase-mimic compound TEMPOL on oxidant stress
      mediated endothelial dysfunction.
AB  - The aim of this study was to investigate the effects of oxidant stress on
      endothelium-dependent and endothelium-independent arterial relaxation. For this,
      oxidant stress was generated by preincubation of rat aortic rings (RARs) in
      either 25 mM glucose (mimicking hyperglycemic stress) or 0.5 mM pyrogallol (a
      superoxide generator) and the effects of the superoxide dismutase (SOD)-mimetic
      compound 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy free radical (TEMPOL) on the
      vasorelaxant and cGMP-producing effects of acetylcholine (ACh) and glyceryl
      trinitrate (GTN) in control RARs and RARs exposed to oxidant stress were
      examined. Pyrogallol, and to a lesser extent high glucose concentration, enhanced
      the contractile response of RARs to phenylephrine and markedly inhibited the
      vasorelaxant response to ACh. Although they existed, the inhibitory effects of
      high glucose and pyrogallol on the vasorelaxant response to GTN were less
      profound, especially with pyrogallol. Moreover, both pyrogallol and high glucose
      concentration inhibited the basal and the ACh-induced vascular cyclic guanosine
      monophosphate (cGMP) production. Treatment with TEMPOL (1-5 mM) slightly
      increased the ACh and GTN-induced cGMP levels in control RARs but had a
      significant effect in high glucose and pyrogallol-pretreated RARs. Additionally,
      concomitant treatment of RARs with TEMPOL (5 mM) abolished the difference in the
      relaxation response between control RARs and RARs exposed to either pyrogallol or
      high glucose concentration. These results further support the theory that
      reactive oxygen species (ROS), especially superoxide, play a key role in
      mediation of endothelial dysfunction accompanying diabetes, probably through
      their effects on the ability of the endothelium to synthesize, release or respond
      to endogenous nitric oxide (NO) or NO donated by nitrovasodilators.

PMID- 11228751
TI  - Endogenous and new synthetic antioxidants for peroxynitrite: selective inhibitory
      effect of 5-methoxytryptamine and lipoic acid on tyrosine nitration by
      peroxynitrite.
AB  - The inhibitory effects of endogenous and synthetic compounds on the nitration and
      oxidation of L-tyrosine by peroxynitrite were examined. Nitration and oxidation
      activities of L-tyrosine by peroxynitrite were estimated by monitoring the
      formation of 3-nitrotyrosine and dityrosine with a high-performance liquid
      chromatography-ultraviolet (HPLC-UV)-fluorescence detector system. Glutathione
      and synthetic compounds ((2S,3R,4S)-N-ethylmercapto-3,4-dihydroxy-2
      hydroxymethylpyrrolidine, L-N-dithiocarboxyproline) inhibited both the nitration
      and the oxidation reactions of L-tyrosine effectively. On the other hand, 5
      methoxytryptamine and lipoic acid inhibited only the nitration reaction of L
      tyrosine, and instead increased the oxidation reaction. It was assumed that 5
      methoxytryptamine and lipoic acid reacted only with the nitrating species of
      peroxynitrite. This is the first report of a selective inhibitor for the
      nitrating reaction of peroxynitrite.

PMID- 11228752
TI  - Liver immunity and glutathione.
AB  - Redox processes have been implicated in various biologic processes, including
      signal transduction, gene expression, and cell proliferation, and several
      molecules have been identified as redox regulators in cell activation.
      Glutathione is the oldest and most investigated molecule among them. Although
      details of the mechanisms by which glutathione regulates various aspects of cell
      biology remains to be characterized, the relationship between immunodeficiency
      and cellular glutathione status is well established. Redox dysregulation
      contributes to the pathogenesis of acquired immunodeficiency syndrome (AIDS).
      Human immunodeficiency virus (HIV)-infected patients and simian immunodeficiency
      virus (SIV)-infected rhesus macaques have, on the average, significantly
      decreased plasma cysteine and intracellular glutathione levels. Liver contains
      abundant levels of reducing factors. However, glutathione levels in serum and
      peripheral blood mononuclear cells of cirrhosis patients are lower compared to
      values detected in healthy individuals. In the present article, the significance
      of glutathione in regulating the functions of lymphocytes, especially those of
      liver-associated lymphocytes, has been described. A novel strategy for immune
      therapy of liver neoplasms with the use of redox-modulating agents has been
      proposed.

PMID- 11228753
TI  - Dyslipidaemia and cardiovascular risk in diabetes.

PMID- 11228754
TI  - Sulphonylurea-induced hypoglycaemia in type 2 diabetes mellitus: a review.

PMID- 11228755
TI  - 5-HT2C receptor modulation and the treatment of obesity.

PMID- 11228756
TI  - Effect of acarbose on additional insulin therapy in type 2 diabetic patients with
      late failure of sulphonylurea therapy.
AB  - AIM: The present study investigated the effect of acarbose on insulin
      requirements and glycaemic control in patients with type 2 diabetes receiving
      exogenous insulin due to secondary failure of maximum dose sulphonylurea therapy.
      METHODS: A single-centre, double-blind, randomized, placebo-controlled study was
      performed in 48 type 2 diabetic patients with late-term failure following at
      least 3 years of sulphonylurea therapy requiring additional insulin therapy to
      determine the impact of acarbose on glycaemic control and insulin requirements.
      The primary end points were glycaemic response rate (responders being predefined
      as patients who achieve a decrease in HbA1c to less than 8% or a reduction by at
      least 15% as compared to the baseline values) and the daily insulin dose at 6
      months. Secondary parameters assessed included postprandial changes in blood
      glucose, serum insulin and C-peptide during the treatment period. RESULTS: There
      were significantly more responders in the acarbose-treated group compared with
      the placebo group (20/24 patients vs. 10/19 patients; p < 0.05). The mean daily
      insulin dose after 24 weeks of treatment was 16.4 +/- 10.1 IU in the acarbose
      group and 22.4 +/- 12.2 IU in the placebo group (mean +/- s.d.; p < 0.07).
      Postprandial increases in blood glucose, insulin and C-peptide were consistently
      lower in the acarbose-treated group than in the placebo group. For example, the
      mean increase in 2-h postprandial serum insulin remained almost unchanged in the
      acarbose group at the end of 24 weeks of treatment compared to an increase to 43
      +/- 29 microU/ml (mean +/- s.d.) at the end of the study period for the placebo
      group. CONCLUSIONS: The findings of this study suggest that the addition of
      acarbose to sulphonylurea/insulin combination therapy can improve glycaemic
      control in type 2 diabetic patients. Acarbose may also reduce insulin resistance
      and hyperinsulinaemia.

PMID- 11228757
TI  - Effect of diabetes on vitamin B6 requirement in experimental animals.
AB  - AIM: In the diabetic state, energy must be supplied mainly by amino acids and
      fat; therefore the metabolic processes are very similar to those of animals fed a
      high-protein diet. Vitamin B6-dependent enzymes, which are highly involved in
      amino acid metabolism, are important in diabetics. We investigated vitamin B6
      content, and aspartate aminotransferase and glycogen phosphorylase activities, in
      several tissues of streptozotocin-induced diabetic and control rats. METHODS: The
      rats were fed a vitamin B6-free diet and administered an equivalent amount of
      pyridoxine based on body weight. RESULTS: Vitamin B6 content in all tissues
      examined, except for the liver, was lower in the diabetics than in controls.
      Aspartate aminotransferase activity was higher in the liver of diabetics than in
      the controls, but not in the other tissues. Glycogen phosphorylase activity in
      the gastrocnemius muscle of diabetics decreased to two-thirds of the control
      level. CONCLUSIONS: These data might indicate that diabetic animals should have a
      higher intake of vitamin B6 because a diabetic state can lead to a vitamin B6
      deficiency.

PMID- 11228758
TI  - Effects of antihyperglycaemic therapies on proinsulin and relation between
      proinsulin and cardiovascular risk factors in type 2 diabetes.
AB  - AIM: To assess the effect of oral antihyperglycaemic therapy on fasting
      proinsulin and the relation between proinsulin levels and cardiovascular risk
      factors in type 2 diabetes. METHODS: One hundred and sixty-five patients with
      type 2 diabetes, fasting blood glucose concentration (FBG) > or = 6.7 mmol/l,
      were recruited from five diabetes outpatient clinics in primary health care. Diet
      and antihyperglycaemic medication, aiming at FBG < 6.7 mmol/l, was maintained for
      6 months after completed dose titration in a randomized, double-blind, double
      dummy trial with metformin (M), glibenclamide (G) and primary combination of both
      drugs (MG). The study compared M, G and MG in low dose (MGL) and also different
      high-dose regimens, i.e. G added to M (M/G), M added to G (G/M) and primary
      combination (MGH). Outcome measures were fasting proinsulin, glycaemia, body mass
      index, blood pressure, lipids, insulin and C-peptide. RESULTS: Lower proinsulin
      levels were found when therapy was initiated with metformin (M vs. G, p = 0.013
      and M/G vs. G/M, p = 0.033). M and G were equally effective on glucose levels. In
      the group as a whole FBG decreased from (mean +/- s.d.) 10.2 +/- 2.7 to 7.0 +/-
      1.2 mmol/l with no change in proinsulin. Proinsulin was associated with
      cardiovascular risk factors, linking high proinsulin to an atherogenic risk
      marker profile. Mean proinsulin change from baseline was inconsistently
      associated with markers of insulin resistance. Meal-stimulated glucose (net AUC)
      decreased after treatment only in those with low baseline proinsulin levels.
      CONCLUSION: It may be advantageous to initiate oral antihyperglycaemic therapy
      with metformin rather than with sulphonylurea. High proinsulin levels are
      associated with an atherogenic-risk marker profile and an impaired therapeutic
      postprandial glucose response after treatment in patients with type 2 diabetes.
      Proinsulin change after therapy is inconsistently associated with markers of
      insulin resistance and unrelated to fasting blood glucose reduction.

PMID- 11228759
TI  - Long-term oral administration of dehydroepiandrosterone has different effects on
      energy intake of young lean and obese male Zucker rats when compared to controls
      of similar metabolic body size.
AB  - AIM: The effects of dehydroepiandrosterone (DHEA) on appetite and weight in the
      Zucker rat have been examined by many investigators who have reported appetite
      suppression and metabolic effects. However, these studies compared the treated
      animals to controls of a similar age. Since animals of different sizes consume
      different amounts of food, perhaps the treated animals should be compared to
      controls of a similar size. We studied the effects of DHEA on energy intake and
      weight gain and analysed the effects by age and metabolic body size. METHODS:
      Lean (n = 21) and obese (n = 16) male Zucker rats were fed plain chow or chow
      containing 6 g DHEA/kg chow (0.6% wt/wt) from age 4 wk to 20 wk. Daily energy
      intakes and body weights were determined at least once weekly. RESULTS: As
      expected, the lean and obese rats given DHEA exhibited less daily energy intake
      (kJ/d) and less weight gain than their respective controls of the same age. The
      lean rats given DHEA did not exhibit any difference in daily energy intake when
      determined relative to body weight (b.w.) (kJ x d-1 x g b.w.-1) compared to lean
      controls of the same metabolic body size, while the obese rats given DHEA
      exhibited less daily energy intake relative to b.w. (kJ x d-1 x g b.w.-1)
      compared to obese control of the same metabolic body size. CONCLUSIONS: Though
      DHEA reduced total energy intake among the lean and obese Zucker rats, only the
      obese rats exhibited less energy intake relative to b.w. compared to controls of
      the same metabolic body size. Thus, DHEA may exert different effects on energy
      intake relative to b.w. in lean and obese Zucker rats and perhaps the lean Zucker
      rat is a better model for evaluating the metabolic effects of DHEA since it does
      not exhibit any effect on energy intake relative to b.w. compared to rats of the
      same metabolic body size.

PMID- 11228760
TI  - Testosterone and leptin in a group of Chinese with and without diabetes.
AB  - AIM: Leptin levels in the overweight and differences between men and women may be
      confounded by sex hormones in obesity-related type 2 diabetes. We carried out a
      study of leptin and testosterone and the effect of diabetes on this relationship
      in 71 Chinese subjects (51 with type 2 diabetes and 20 healthy non-diabetics) of
      whom 32 were overweight (body mass index (b.m.i.) > 25.0 kg/m2). METHODS AND
      RESULTS: Leptin levels were similar in the diabetic (median 7.4, interquartile
      range 4.2-10.6 ng ml-1) and non-diabetic (11.3 (6.0-16.3) ng ml-1) subjects.
      Testosterone and free testosterone in diabetics and non-diabetics were similar
      for both gender. Regardless of diabetes status, testosterone and its free form
      tend to increase in overweight women and decrease in men. Leptin correlated with
      testosterone in women with diabetes (Pearson correlation coefficient r = 0.495, p
      = 0.037) but not in diabetic men. Sixty-eight per cent of leptin variance was
      affected by b.m.i, insulin, sex (female) and diabetes status in a regression
      model that excluded testosterone (total and free). However, testosterone and
      insulin were predictors of leptin changes in the non-diabetic subjects. In
      diabetes, b.m.i., sex (female) and insulin remained as predictors of leptin
      changes. CONCLUSIONS: These results suggest that apart from body adiposity,
      testosterone also influences leptin levels and that diabetes has a significant
      effect on this association.

PMID- 11228761
TI  - An interdisciplinary approach to breast and PCA. International Symposium: Breast
      and PCA: Genes, Hormones and the Environment, Garmisch-Partenkirchen, Germany, 22
      24 April 1999.
AB  - Breast and prostate cancer (PCA) are among the leading cancer forms in the
      developed world. The 'International Symposium: Breast and PCA: Genes, Hormones
      and the Environment', and interdisciplinary meeting organized by K. Badenhoop
      (University Hospital, Frankfurt, Germany), J. Kohrle (University Hospital,
      Wurzburg, Germany) and W-D. Schleuning (Schering AG, Berlin, Germany), was
      intended to promote the exchange of new concepts and emerging paradigms between
      basic science and clinical research, and to establish interactions with
      researchers in industry in this field.

PMID- 11228762
TI  - Cellular and molecular events surrounding blastocyst implantation: report on a
      NICHD meeting, Bethesda, MD, USA, 15-16 November 1999.
AB  - This meeting, supported by the Reproductive Sciences Branch, Center for
      Population Research, National Institute of Child Health and Human Development
      (NICHD), NIH, was held to achieve dual purposes: (1) the evaluation of the
      ongoing National Cooperative Program on Markers of Uterine Receptivity for
      Blastocyst Implantation and (2) to update our knowledge of blastocyst
      implantation research. The Cooperative Program was evaluated as being highly
      successful, with good productivity, rapid exchange of information, and remarkable
      progress. Our knowledge of many molecules that concern interactions between
      blastocyst and maternal tissues was also updated as a result of the meeting.

PMID- 11228763
TI  - Bone Disease on the web.

PMID- 11228764
TI  - Hyperactivity in children: a focus on genetic research and psychological
      theories.
AB  - Hyperactivity has attracted a large amount of research interest in recent years.
      Here we review developments in genetic research and in research testing
      psychological theories of the condition. Family, adoptee and twin studies
      indicate a strong role for genetic factors in the etiology of hyperactivity.
      Evidence is emerging also from molecular genetic studies, implicating specific
      genes that may be involved. At the level of cognitive functioning, a divided,
      focused or sustained attention deficit does not seem to be a 'core' deficit in
      hyperactivity. Although children with hyperactivity often perform poorly on
      certain executive function tasks, there is disagreement about the interpretation
      of these findings. The association reported in some studies between a slow
      inhibitory process and hyperactivity may reflect a generally slow, variable in
      speed and inaccurate pattern of responding. Hypotheses about psychological
      mechanisms such as state regulation or delay aversion provide alternative, and
      particularly encouraging, interpretations of the findings. We discuss the
      possible integration of the two lines of research--those of genetic research and
      research on psychological mechanisms.

PMID- 11228765
TI  - Intervention models for mothers and children at risk for injuries.
AB  - We review risk factors commonly associated with childhood unintentional injuries
      and highlight adolescent mothers and their young children as a high risk group.
      Several intervention models of injury, including the epidemiological model,
      Peterson and Brown's "working model," and the socioecological model have been
      proposed to explain the events that lead to injuries. Discussion of these models
      is provided and a synthesis of the adolescent parenting model and the
      socioecological model of injury is suggested as way to address the complex
      variables that lead to an injury causing event for adolescent mothers and their
      young children. Finally, we suggest areas of future investigation and their
      implications for prevention and treatment.

PMID- 11228767
TI  - The role of families and care givers as risk and protective factors in preventing
      youth violence.
AB  - This paper reviews research which discusses the risk and protective functions
      that families and other caregivers provide in influencing the development of
      aggressive behavior in youth. Currently, there is an emphasis on providing
      violence prevention programs in the school environment, typically with little
      parental or caregiver involvement. By enhancing the role of families and
      caregivers in youth violence prevention programs, we assert that an unique
      opportunity exists to both address specific risk factors for violence while
      enhancing the protective features of the family. Relatedly, the risk literature
      on youth violence indicates that the most influential risk factors (i.e., the
      family, community, and peers) have their principle impact on youth aggression
      outside the school. We suggest a shift in the focus of violence prevention
      programming that is more inclusive of families as both a risk and protective
      agent. In support of this position, relevant theory and reviews of exemplary
      family-involved programs are offered. Challenges to involving youth caregivers
      are identified and recommendations for overcoming those challenges suggested.
      Last, recommendations for future research and public policy in the prevention of
      youth violence are offered.

PMID- 11228766
TI  - Findings on disruptive behavior disorders from the first decade of the
      Developmental Trends Study.
AB  - The paper summarizes the first decade of the Developmental Trends Study, a
      prospective longitudinal study of 177 boys. Initially, they were referred to
      mental health clinics in Pennsylvania (Pittsburgh), and Georgia (Athens and
      Atlanta). Since 1987, the boys, their parents, and their teachers have been
      followed up almost annually. The study is unique because the cooperation rate of
      participants has remained very high over the years, psychiatric diagnoses were
      derived from structured interviews (especially disruptive behavior disorders),
      and many risk factors were measured over the years. The present paper summarizes
      key findings on the development of disruptive behavior, especially Oppositional
      Defiant Disorder, Conduct Disorder, and Attention Deficit-Hyperactivity Disorder.
      The paper also highlights results on risk factors and comorbid conditions of
      disruptive behaviors.

PMID- 11228768
TI  - Ethical issues in communicating science.
AB  - Most of the publicized work on scientific ethics concentrates on establishing
      professional norms and avoiding misconduct. The successful communication of
      science is the responsibility of all involved in the process. In one study, the
      increased incidence of autism and other social developmental disorders in males
      was investigated by examining individuals with Turner's syndrome (XO females). In
      the national newspaper this became "Genetic X-factor explains why boys will
      always be boys". The steps by which a study on developmental disorders, published
      in a highly prestigious journal, was transformed into an article in the science
      section which 'explained' the socially expected gender-based behavior of
      genetically normal children are fascinating and, unfortunately far too typical.
      The scientists wrote an excellent article that has just one sentence at the end
      that hesitantly suggests that the findings might, with further study, have some
      relevance to understanding normal behavior. The general interest article in the
      front of the journal gave a good account of the research, but suggested more
      strongly that there could be an in-built biological dimorphism in social
      cognition. This was misrepresented in the press as proof of gender differences
      that "undermines the trend towards sexual equality", and both illustrates
      cultural bias and provides fodder for feminist critiques of science. The study
      has been made to appear to be biased in favor of justifying the social structure
      of society, and yet it was the translation from the scientific study to national
      news that produced this transformation to biased genetic determinism. It is poor
      communication of the actual science, coupled with a lack of skepticism on the
      part of the public, that contributes to such a misapplication of science.
      Scientists should resist the urge to generalize their results to make them more
      compelling. The science community should not allow misconstructions of scientific
      facts to go unchallenged. Journalists, for both the scientific publication and
      the newspaper, should resist the inclination to embellish the finding with social
      significance that is not present. For their part, readers must be doubly
      skeptical of any finding that appears to underwrite any current social hierarchy.
      We are all responsible for a communication and interpretation of science that is
      as accurate and socially responsible as possible.

PMID- 11228769
TI  - Normative orientations of university faculty and doctoral students.
AB  - Data from two national surveys of 4,000 faculty and doctoral students in
      chemistry, civil engineering, microbiology and sociology indicate that both
      faculty and students subscribe strongly to traditional norms but are more likely
      to see alternative counternorms enacted in their departments. They also show
      significant effects of departmental climate on normative orientations and suggest
      that many researchers express some degree of ambivalence about traditional norms.

PMID- 11228770
TI  - Transforming science curricula in higher education: feminist contributions.
AB  - Feminist contributions to the science curricula in higher education constitute
      invaluable but often overlooked resources for truly effective communication about
      science. Here I share a sampling of feminist science studies and discuss the
      origins of this effort to create inclusive and less biased science curricula that
      serve all students and citizens. Challenges from scientists center on assumptions
      and values about the appropriate relationship between science and politics, while
      challenges from educators extend to assumptions about how science has been
      taught. Currently, national and local curriculum transformation efforts are
      producing useful insights and materials.

PMID- 11228771
TI  - Talking about race in a scientific context.
AB  - There are at least two approaches that assist students in understanding
      complexity and differing interpretations about human diversity and race. Because
      differing perspectives emerge from data perceived at different levels, different
      scales provide a tool for understanding relationships among perspectives and
      understanding the differential importance of specific factors. Constructivist
      listening, which assists students in examining their own experiences, feelings
      and understanding, provides a tool for digesting complex new material and
      learning emotional literacy. It can be applied to dialogue about race and to
      classroom situations. These approaches can help students master the conceptual
      and interpersonal skills needed for successful scientific practice.

PMID- 11228772
TI  - Talking and teaching about human biological variation commentary on "Talking
      about race in a scientific context".

PMID- 11228773
TI  - The politics of certainty: conceptions of science in an age of uncertainty.
AB  - The prestige of science, derived from its claims to certainty, has adversely
      affected the humanities. There is, in fact, a "politics of certainty". Our
      ability to predict events in a limited sphere has been idealized, engendering
      dangerous illusions about our power to control nature and eliminate time. In
      addition, the perception and propagation of science as a bearer of certainty has
      served to legitimate harmful forms of social, sexual, and political power. Yet,
      as Ilya Prigogine has argued, renewed attention to the irreducible reality of
      time has brought us to "the end of certainty". As we enter the age of
      uncertainty, there is disagreement about how science should be understood and
      communicated. Some scientists cling to the ideal of certainty, while others
      emphasize the creative potential of spontaneity, novelty, and surprise.

PMID- 11228774
TI  - The Golem: uncertainty and communicating science.
AB  - This paper elaborates on the golem metaphor as a way of understanding uncertainty
      in science. Its implications for the ethics of communicating science are
      explored.

PMID- 11228775
TI  - Seeds of discontent: expert opinion, mass media messages, and the public image of
      agricultural biotechnology.
AB  - Survey data are presented on opinions about agricultural biotechnology and its
      applications held by agricultural science faculty at highly ranked programs in
      the United States with and without personal involvement in biotechnology-oriented
      research. Respondents believed biotech holds much promise, but policy positions
      vary. These results underscore the relationship between opinion and stakeholder
      interests in this research, even among scientific experts. Media accounts are
      often seen as causes, rather than artifacts, of the existence of public
      controversy; European and now U.S. opposition to food biotechnology is often
      explained away in terms of such a relationship. The authors argue that where even
      experts are divided, public opposition cannot reasonably be attributed to poor
      public understanding or sensationalistic media accounts. Ethical implications for
      communicating science are explored.

PMID- 11228776
TI  - Improving the scientist/journalist conversation.
AB  - How well do scientists communicate to members of the mass media? A communication
      scholar reviews potential barriers to the essential dialogue necessary between
      those in the sciences and journalists who report science to the public.
      Suggestions for improving communication within this relationship, in spite of
      professional process differences, are offered, emphasizing adherence to shared
      ethical standards.

PMID- 11228777
TI  - Why scientists should cooperate with journalists.
AB  - Despite a widespread impression that the public is woefully ignorant of science
      and cares little for the subject, U.S. National Science Foundation (NSF) surveys
      show the majority are very interested and understand that they are not well
      informed about science. The data are consistent with the author's view that the
      popularity of pseudoscience does not indicate a rejection of science. If this is
      so, opportunities for scientists to communicate with the public promise a more
      rewarding result than is commonly believed among scientists. In fact, the
      increasing visibility of science in the mass media correlates with a slow, steady
      improvement in public understanding of science in recent years.

PMID- 11228778
TI  - Making the audience a key participant in the science communication process.
AB  - The public communication of science and technology has become increasingly
      important over the last several decades. However, understanding the audience that
      receives this information remains the weak link in the science communication
      process. This essay provides a brief review of some of the issues involved,
      discusses results from an audience-based study, and suggests some strategies that
      both scientists and journalists can use to modify media coverage in ways that can
      help audiences better understand major public issues that involve science and
      technology.

PMID- 11228779
TI  - [Transrectal ultrasonography of the prostate].

PMID- 11228780
TI  - [Blood transfusion. Indications and blood utilization].

PMID- 11228781
TI  - [Strategies to reduce the use of perioperative allogenic blood].
AB  - Allogenic blood transfusion carries the risk of immunological and non
      immunological adverse effects. Consequently, blood transfusion should be limited
      to situations where alternatives are not available. This article reviews current
      by available alternative strategies that reduce the need for perioperative
      allogenic blood transfusion. The effectiveness of a number of these alternatives
      needs to be documented and potential adverse effects clarified. The acceptance of
      a lower haemoglobin level as the transfusion trigger value is perhaps the most
      important factor in reducing the need for peri-operative allogenic blood
      transfusion.

PMID- 11228782
TI  - [Gene therapy in future surgery].

PMID- 11228783
TI  - [The significance of oxygen for wound healing and development of wound
      infection].

PMID- 11228784
TI  - [Clinical examination of the knee--which tests can be used in the diagnosis of
      meniscal and ligament injuries? ].
AB  - The clinical diagnosis of possible meniscal tear should include more than one of
      the following positive tests or clinical symptoms: tenderness of either
      jointline, swelling of the knee; meniscal pain or clicking on rotation with
      movement or decreased motion of the knee joint. The diagnosis of ligament
      injuries should include testing of each ligament by a battery of tests and we
      describe the best validated of these tests for each ligament.

PMID- 11228785
TI  - [Surgical physiopathology. New results of importance for optimization of the
      postoperative course].
AB  - Complications after major surgery may be related to factors in the surgical
      stress response with endocrine-metabolic and inflammatory changes. In order to
      prevent these complications, it is important to understand the stress reaction of
      each organ system. The inflammatory response may be partly prevented by a minimal
      invasive surgical technique or by preoperative administration of high-dose
      steroids. Prevention of the endocrine-metabolic changes is best achieved with
      neural blockade. Unimodal intervention cannot eliminate morbidity and mortality
      after major surgery. Thus, multi-modal intervention with attenuation of the
      surgical stress response, effective dynamic treatment of pain, enforced
      mobilisation, and nutrition should be employed when possible.

PMID- 11228786
TI  - [Accelerated rehabilitation after colon resection].
AB  - INTRODUCTION: The stay in hospital after colonic resection is usually 7-12 days,
      with a complication rate of 20%. A multi-modal rehabilitation regimen, comprising
      epidural analgesia, early mobilisation, and oral nutrition, reduced the hospital
      stay to 2-3 days after colonic resection. METHODS: One hundred patients underwent
      elective colonic resection with a planned postoperative stay of two days in
      hospital and a regimen with epidural analgesia, oral nutrition, and mobilisation.
      Anaesthesia, the surgical technique, and nursing care programme were
      standardised. Postoperative follow-up visits were arranged for day 8 and day 30.
      RESULTS: The median age was 73 years. Forty patients were at high risk, ASA III
      IV. Gastrointestinal function (defecation) occurred within 48 hours, except for
      five patients, and the median hospital stay was two days. The readmission rate
      was 18% with no acute, potentially lethal conditions. The total hospital stay was
      three days. None of the patients had cardiopulmonary complications, except for
      one patient, who died from cardiac failure 36 hours after surgery. Three patients
      had anastomotic dehiscence, two of whom were treated conservatively. CONCLUSION:
      The usual postoperative ileus, "medical complications", and hospital stay were
      reduced in high-risk patients undergoing colonic resection with a multi-modal
      rehabilitation programme. These results call for further comparative studies with
      conventional care programmes and laparoscopic colonic resection.

PMID- 11228787
TI  - [Treatment of morbid obesity with laparoscopic, adjustable gastric banding.
      Results after two years of experiences with a new surgical method for severe
      obesity].
AB  - INTRODUCTION: In the last decade, laparoscopic, adjustable silicone gastric
      banding for morbid obesity has gained widespread use, owing to two important
      improvements: The surgical procedure can be performed laparoscopically and the
      weight loss can be regulated by adjusting the silicone band by a simple
      percutaneous technique. MATERIAL AND METHODS: Over a 2-year period, we followed
      up 33 patients admitted to the clinic for morbid obesity. Sixteen patients
      preferred the conventional diet treatment (1), seven patients underwent an
      operation (2), and ten patients were motivated for operation, but were found to
      be unfit and were treated by diet (3). RESULTS: The excess loss of body weight
      was 25% in group 1, 60% in group 2, and 0% in group 3. CONCLUSION: Laparoscopic,
      adjustable gastric banding can help the severely obese patients when diets and
      pharmacological treatment have failed. The resulting loss of weight is highly
      dependent on careful follow-up by a professional obesity team.

PMID- 11228788
TI  - [Treatment of phimosis with a steroid creme in boys].
AB  - The current treatment of phimosis in Denmark is surgical. Reports of success
      rates of 70-80% with topical steroids have prompted us to carry out the present
      study. METHODS: Parents of boys, who were referred because of phimosis,
      volunteered to participate in an open trial of topical clobetasol 0.05%, along
      with gentle mobilisation of the foreskin once daily for 4-6 weeks. Fifty-five
      boys completed the treatment. The results were recorded at clinical follow-up
      four and six weeks later, and a long-term follow-up was done by questionnaire
      sent after 9-11 months. RESULTS: At six weeks of treatment, 42 had a fully
      retractable foreskin, 11 a partially retractable foreskin, and two had unchanged
      phimosis. Ten patients had a circumcision or plasty. At long-term follow-up, 12
      had a symptomatic recurrence. Four of these were given surgical treatment and
      eight had a repeat topical treatment, which was effective in six. The overall
      effect was independent of the degree of phimosis. Four patients with obvious
      sacrified foreskin failed. Twelve patients had agglutinations, which became
      apparent after the treatment for phimosis. We recorded no systemic and very few
      local side effects. The patients and parents found the treatment convenient and
      satisfactory. CONCLUSION: Topical clobetasol 0.05% once a day for 4-6 weeks can
      be recommended as primary treatment in phimosis in boys without scarification of
      the foreskin. The treatment may be repeated as necessary.

PMID- 11228789
TI  - [Percutaneous transluminal embolization of pulmonary arteriovenous
      malformations].
AB  - OBJECTIVE: The aim was to evaluate the effect of embolisation of pulmonary
      arteriovenous malformations (PAVM), as estimated by contrast echocardiography,
      arterial blood-gas analyses and functional level, and further to evaluate
      procedure-related and late complications. PATIENTS AND METHODS: Seventeen
      patients were treated on 25 occasions for a total of 48 PAVM. Fifteen patients
      had hereditary haemorrhagic telangiectasia (HHT). Chest X-ray, pulmonary
      angiography, contrast echocardiography, arterial blood-gas analyses, and
      functional level were analysed before and after embolisation of PAVM. The mean
      follow-up period was 22 months. RESULTS: Contrast intensity at contrast
      echocardiography decreased from median 4.0 (range 2-4) before embolisation to 1.5
      after embolisation. PaO2 breathing 100% oxygen increased from mean 271 mm Hg
      before embolisation to 480 mm Hg after embolisation. The shunt was reduced from
      mean 24% before to 12% after embolisation. Most of the patients experienced an
      increased functional level after embolisation, and the median functional level
      (NYHA) increased from NYHA 2.5 to 1.2. No primary or secondary device migration,
      no cerebral insults, and no mortality was noted. CONCLUSION: Embolisation is a
      well-established method of treating PAVM, with a significant effect on
      oxygenation of the blood. It is a minimally invasive, lung-preserving treatment
      with high affectiveness and low morbidity and mortality. Patients with HHT should
      be screened for PAVM as a high percentage of these have PAVM.

PMID- 11228790
TI  - [Premedication in ambulatory surgery].
AB  - A substantive amendment to this systematic review was last made on 3 January
      2000. Cochrane reviews are regularly checked and updated if necessary.
      OBJECTIVES: To assess the effect of anxiolytic remedication on time to discharge
      in adult patients undergoing day case surgery under general anaesthesia. SEARCH
      STRATEGY: Trials were identified by computerised searches of the Cochrane
      Controlled Trials Register, MEDLINE, EMBASE, by checking the reference lists of
      trials and review articles, by handsearching three main anaesthesia journals and
      by contacting five researchers active in the field and the Product Information
      departments of the manufactures of five commonly used premedicants. SELECTION
      CRITERIA: All randomised controlled trials comparing an anxiolytic drug(s) with
      placebo before general anaesthesia in adult day case surgical patients. DATA
      COLLECTION & ANALYSIS: We collected data on anaesthetic drugs used, results of
      tests of psychomotor function where these were used to assess residual effect of
      premedication, and on times from end of anaesthesia to ability to walk unaided or
      readiness for discharge from hospital. Formal statistical synthesis of individual
      trials was not performed in view of the variety of drugs studied. MAIN RESULTS:
      Searching identified twenty-nine reports; fourteen studies, with data from a
      total of 1263 patients, were considered eligible for analysis. Only two studies
      specifically addressed the discharge question; both found no delay in
      premedicated patients. Three other studies used clinical criteria to assess
      fitness for discharge, though times were not given. Again, there was no
      difference from placebo. Four studies used both clinical measures and tests of
      psychomotor function as tests of recovery from anaesthesia. In none of these
      studies did the premedication appear to delay discharge, although performance on
      tests of psychomotor function was sometimes still impaired. Of the four studies
      which used tests of psychomotor function to assess recovery, three showed
      impaired recovery (after midazolam 7.5 mg, midazolam 15 mg or diazepam 15 mg)
      which might possibly interfere with discharge from hospital. REVIEWERS'
      CONCLUSIONS: We have found no evidence of a difference in time to discharge from
      hospital in patients who received anxiolytic premedication. However, in view of
      the age and variety of anaesthetic techniques used, inferences for current day
      case practice should be made with caution.

PMID- 11228791
TI  - [Traumatic pseudoaneurysm of the peroneal artery].
AB  - Traumatic arterial pseudo-aneurysm is a rare phenomenon. We describe a case of
      pseudoaneurysm of the peroneal artery as a late complication to an open crural
      fracture. Persistent or occurrence of swelling, pain, paraesthesias or sensory
      deficit at the fracture site should be considered symptoms of a developing
      arterial pseudo-aneurysm. The presence of a distal pulse and negative results of
      ultrasound examination in the Doppler modality does not rule out arterial pseudo
      aneurysm, therefore arteriography is often indicated. Treatment of traumatic
      arterial pseudo-aneurysms is surgical, as they often tend to progress.

PMID- 11228792
TI  - [Picture of the month: colon cancer].

PMID- 11228793
TI  - [Prevention of thrombosis in hip alloplasty].

PMID- 11228794
TI  - [Neonatal pneumothorax].

PMID- 11228796
TI  - [Why should surgeons publish?].

PMID- 11228795
TI  - [Standard prevention of thrombosis in hip and knee alloplasties].

PMID- 11228797
TI  - [Evidence-based surgery].
AB  - The justification for performing surgery on patients most often rests on
      observational studies and rarely on correctly conducted randomised trials, which
      is the highest level of evidence. For methodological and ethical reasons,
      surgical trials can be problematic. However, the ethical problems are greater if
      trials are not performed, since it will then not be possible to find out which of
      the available interventions have no effect or are harmful. The problems can be
      overcome in many cases, and by intra- and international co-operation it would be
      possible to carry out many more trials, which would increase the level of
      evidence for surgery in daily practice. When randomised trials have not been
      performed, one is obliged to look for the evidence in prospective cohort studies,
      e.g. clinical databases, which, however, are more suitable for evaluating
      complications to surgery under routine circumstances than for evaluating useful
      effects.

PMID- 11228798
TI  - [Development and challenges in abdominal surgery].

PMID- 11228799
TI  - [New minimally invasive urologic procedures].

PMID- 11228800
TI  - [Minimally invasive vascular surgery--endovascular surgery].

PMID- 11228801
TI  - [Subfascial endoscopic supplementary surgery of perforating veins. Experiences
      with the first 100 procedures].
AB  - INTRODUCTION: Leg ulcers following varicose veins and incompetent perforators
      have been treated by supplementary surgery of the perforators, originally by open
      operation, from the early eighties by endoscopic techniques. METHODS: The
      endoscopic operation is carried out through a short incision of the skin and
      fascia well above the skin changes, and consists of subfascial electro
      cauterization and cutting of the incompetent perforators. RESULTS: 100
      consecutive procedures were performed 1995-1999. Totally, the frequency of
      complications was 28%, mostly minor and self-limiting: Haematoma/haemorrhage 6%,
      infection 9%, deep vein thrombosis 1%, sural and saphenous nerve affection 9% and
      others 3%. With a median follow-up of 10 months, 94% of the patients were
      satisfied with the treatment, 5% experienced unchanged symptoms, 1% became worse.
      In 30 ulcer-cases, 80% were without recurrency after a median follow-up of 16
      months, the rest having recurrent, but smaller ulcers. CONCLUSION: The present
      results are similar to the experience reported by others. It is suggested that
      the technique may be developed in centers for advanced varicose vein surgery.

PMID- 11228802
TI  - [Coronary artery bypass without use of the heart-lung-machine].
AB  - INTRODUCTION: Off pump coronary artery bypass via sternotomy (OPCAB) and via a
      small left anterior thoracotomy (MIDCAB) on the anterior coronary arteries of the
      heart was introduced at the present center in 1997. Starting this year we decided
      to increase OPCAB and MIDCAB to constitute at least 50% of CAB procedures
      including the posterior aspect of the heart. METHODS: From January 1st through
      April 16th 1999 we performed 152 CAB procedures: 108 CABG, 6 MIDCAB, 13 OPCAB (on
      the anterior cornary arteries) and 25 OPCAB-Cx (including the circumflex artery).
      OP procedures were done using OCTOPUS-II to expose and stabilize the
      arteriotomies, and control angiography was performed before discharge. RESULTS:
      Off pump CAB was performed in 2% of the first 50 CAB patients, 36% of the next 50
      and 50% of the last 52. The CABG and OPCAB-Cx groups were comparable as regards
      degree of coronary artery disease and number of distal anastomoses, but differed
      as regards poor left ventricular function and unstable preoperative status. Early
      mortality was 1.9% in the CABG group and 0% in the OP groups. Control angiograms
      in the OP groups showed a patency from 92 to 100%. CONCLUSIONS: In this short
      preliminary series, it was possible to increase the fraction of OP procedures to
      nearly 50% with good results.

PMID- 11228803
TI  - [Coronary bypass surgery without heart-lung-machine. First experiences and
      results after two years].
AB  - Results and experiences two years after the introduction of off-pump coronary
      artery bypass (OPCAB) are presented. The material includes 95 patients, where 24
      patients had a high preoperative risk due to unstable angina, concomitant
      diseases or relative contraindications to conventional bypass surgery. Per- and
      postoperative course was characterized by low morbidity with ultra fast track
      recovery, no detectable levels of coronary enzyme release in the majority of
      patients, no reoperations for bleeding and early discharge from the hospital.
      There were two in-hospital deaths, both patients from the high risk group, where
      one patient died due to a preoperative myocardial infarction, while the other
      death was not related to cardiac disease. Follow-up results were fully
      satisfactory, where 86% of the patients were free from anginal symptoms three
      months after surgery. As a consequence of these positive experiences, OPCAB
      surgery is offered to an increasing number of patients, currently 25% of our CABG
      procedures.

PMID- 11228804
TI  - [Laparoscopic surgery--an update of current status].
AB  - Recent developments have allowed most intra-abdominal procedures to be performed
      by the laparoscopic technique. Potential clinical advantages are supported by the
      reduced pathophysiological changes demonstrated in the surgical stress response,
      as compared with open surgery. However, a critical assessment of randomised,
      controlled studies and meta-analyses comparing laparoscopic and open surgery has
      not convincingly shown that laparoscopic surgery improves the outcome, except in
      a few operations. Because the concept of minimal invasive surgery is based on
      well-documented pathophysiological advantages, future randomised studies
      comparing laparoscopic and open surgery should include a revision of
      perioperative care regimens with early rehabilitation, in order to demonstrate
      more significant benefits of laparoscopic surgery.

PMID- 11228805
TI  - [Complications of cholecystectomy before and after introduction of laparoscopic
      surgery].
AB  - OBJECTIVES: In the University Department of Surgical Gastroenterology, Arhus
      University Hospital, the frequency of complications to acute and elective
      cholecystectomy was investigated before and after introduction of laparoscopic
      cholecystectomy. MATERIAL AND METHODS: A retrospective survey turned up 1768
      patients in the period of conventional open surgery (1974-1985) and 1432 patients
      in the laparoscopic period (1991-1998). All patients with exploration of the
      common bile duct were excluded. RESULTS: In the open period 12 patients (0.68%)
      had lesions of the common bile duct requiring reconstruction. In patients
      operated on with laparoscopic cholecystectomy, lesions of the common bile duct
      were found in three patients (0.21%) (p = 0.06). Lesions of the cystic duct or an
      aberrant bile duct occurred in 14 patients (0.79%) during the open period and in
      24 patients (1.7%) (p < 0.05) operated on with the laparoscopic technique.
      Infectious and cardiopulmonary complications were seen in significantly more
      patients operated on with the open technique. DISCUSSION: It is concluded that
      laparoscopic cholecystectomy offers a safe procedure, although the technique can
      still be improved, especially with respect to decreasing leakage from the cystic
      duct.

PMID- 11228806
TI  - [Gastrointestinal endoscopy--review and perspectives].
AB  - Gastrointestinal endoscopy comprises gastroscopy, colonoscopy, and endoscopic
      retrograde cholangiopancreatography (ERCP). Endoscopic ultrasonography and small
      bowel enteroscopy are also available, although not in all endoscopy units. The
      diagnostic accuracy of gastrointestinal endoscopy is very high. Scientific
      activities include evaluation of methods/regimens where diagnostic gastroscopy
      can be replaced by non-invasive Helicobacter screening for certain patients, the
      use of non-invasive alternatives to ERCP (e.g. magnetic resonance), small bowel
      enteroscopy without the use of an endoscope, and virtual colonoscopy with
      computer tomography or magnetic resonance techniques. The move away from
      traditional endoscopic procedures towards more non-invasive techniques is taking
      place along with the development of new endoscopic procedures to replace
      traditional surgical techniques, e.g. endoscopic placement of colonic metal
      stents in acute colonic obstruction.

PMID- 11228807
TI  - [Flexible sigmoidoscopy in Denmark. A questionnaire].
AB  - AIM: To assess the use of flexible sigmoidoscopy in Denmark in 1997. METHODS: A
      country wide questionnaire was mailed to all hospitals and specialists in surgery
      and gastroenterology. RESULTS: The response rate was 96%. Thirteen thousand one
      hundred and eighty-one flexible sigmoidoscopies were done. However, this number
      was much too small in order to examine all persons with colonic symptoms. Two
      severe complications were reported. CONCLUSIONS: A substantial extension of the
      flexible sigmoidoscopy service is needed to comply with the recommendations from
      the Danish National Board of Health to replace rigid proctoscopy with flexible
      sigmoidoscopy in the diagnostic strategy.

PMID- 11228808
TI  - [Quality of colonoscopy and surgical treatment of perforations].
AB  - INTRODUCTION: Perforation during colonoscopy is a well-known complication. The
      purpose of our study was to evaluate the incidence of acute surgical intervention
      due to colonic perforations during endoscopy at our department, and evaluate the
      rate of incomplete examinations. METHODS: The latest 4000 colonoscopies performed
      at Hvidovre Hospital were examined for possible complications and success rate.
      RESULTS: Seventeen percent of the colonoscopies were incomplete, mostly due to
      anatomical difficulties, incomplete bowel preparation, and pain. Twelve (0.3%) of
      the 4000 patients were operated on due to perforation which occurred during the
      examination. The mortality rate in these 12 patients was 17% and the survivors
      had a median hospital stay of eight days. DISCUSSION: Future strategy should
      focus on improving the quality of colonoscopy, thereby increasing the success
      rate and lowering patient discomfort. Furthermore, the new non-invasive
      modalities virtual colonoscopy (CT or MRI) should be developed further so that
      they might substitute all the diagnostic colonoscopies.

PMID- 11228809
TI  - [Breast conserving surgery in breast cancer].

PMID- 11228810
TI  - [Balkanitis].

PMID- 11228811
TI  - [Concerning the use of linseed/oil as dietary supplementation].

PMID- 11228812
TI  - [Aspiration biopsy versus excision biopsy].

PMID- 11228813
TI  - [Laparoscopic surgery and research. A study visit to the Yale University].

PMID- 11228814
TI  - Stats and facts. Obesity as an insidious and spreading health pandemic.

PMID- 11228815
TI  - Solving the military's health care dilemma for Medicare eligibles.
AB  - The U.S. military health system has undergone a number of changes; however,
      indications are that more are needed. A major issue is whether the system can
      provide the health care needed to the increasing number of military retirees and
      their family members who are eligible for Medicare. In this paper, the authors
      recommend, based on the reviewed evidence, a possible long-term solution to the
      issues affecting Medicare-eligible military retirees and their family members.

PMID- 11228816
TI  - Formulary decision making and acute exacerbations of chronic bronchitis.

PMID- 11228817
TI  - Workplace costs associated with acute exacerbation of chronic bronchitis: a
      comparison of moxifloxacin and levofloxacin.
AB  - Past research on acute exacerbation of chronic bronchitis (AECB) has not
      quantified related work loss. This exploratory study used data from a comparative
      trial of moxifloxacin versus levofloxacin to examine and compare workplace
      related indirect costs. Both groups reported considerable absenteeism and lowered
      work productivity. However, patients taking moxifloxacin reported significantly
      higher work productivity than those taking levofloxacin (70% vs. 50%; P = .03).
      This translated into substantial indirect cost savings with moxifloxacin of
      $726/patient/year. Antibiotic choice in AECB can affect worker productivity and
      workplace-related indirect costs. Both insurers and employers should consider
      workplace-related indirect costs in addition to direct medical expenses when
      making formulary selections.

PMID- 11228818
TI  - Measuring health care outcomes: the state of the art.

PMID- 11228819
TI  - Asthma outcome changes associated with use of the leukotriene-receptor antagonist
      zafirlukast.
AB  - A new class of asthma drugs modifying the leukotriene pathway was introduced in
      1996. The authors investigated outcome changes associated with use of the
      leukotriene-receptor antagonist zafirlukast. The study group included patients
      with asthma (12-64 yr), most with mild-to-moderate, persistent asthma, who had at
      least two zafirlukast prescriptions within 90 days after the start of zafirlukast
      treatment. Zafirlukast treatment was associated with reductions in occurrence of
      outpatient visits, emergency department visits, inpatient stays, and
      prescriptions for short-acting beta-adrenergic agonists in the next six months
      (all P < .05). A 12-month pre- and post-zafirlukast treatment comparison in a
      smaller group of patients and a classification of patients into three mutually
      exclusive outcome groups (increase, decrease, or no change in outcome events)
      verified the majority of the findings. A cost analysis from a third-party
      perspective indicated that costs of zafirlukast treatment were more than offset
      by cost savings associated with the reductions in outcome events.

PMID- 11228820
TI  - Strategic initiatives for HMOs under mental health carve-outs.
AB  - Many MCOs provide consumers with mental health care benefits--whether internally
      or through an outside vendor. Just having a plan in place is not enough, however.
      The author outlines seven ways that health plans can maximize the benefits of
      mental health coverage while at the same time satisfying members and purchasers.

PMID- 11228821
TI  - The next wave in managed care connectivity.

PMID- 11228822
TI  - Anseriform and galliform therapeutics.
AB  - This article provides the reader with an overview of the therapeutic options for
      members of the orders Anseriformes and Galliformes. These orders make up a large
      variety of nonpsittacine birds that are seen in veterinary practice or in zoos
      and private collections. Standard therapeutics are discussed as well as recently
      developed protocols. Order-specific idiosyncrasies are addressed. A formulary for
      each order is provided by drug category.

PMID- 11228823
TI  - Pet fish formulary.
AB  - Aquarium fish are one of the most popular pets in the United States.
      Understanding the use of chemotherapeutics in these animals has increased
      markedly in recent years, and this information is now readily accessible to the
      private practitioner in this article. The authors introduce the veterinary
      clinician to the commonly used chemotherapeutics, routes of administration,
      species-specific precautions, and treatment tips where appropriate.

PMID- 11228824
TI  - Therapeutics in ferrets.
AB  - The domestic ferret (Mustela putorius furo) continues to grow in popularity as a
      pet species in North America as well as many countries around the world. With
      this rapid growth comes an increased potential for small and exotic animal
      practitioners to expand their ferret clientele. This article reviews the commonly
      used therapeutics in ferrets, as well as the general principles and guidelines
      for their use.

PMID- 11228825
TI  - Therapeutics of African pygmy hedgehogs and prairie dogs.
AB  - The author examines the therapeutics for African pygmy hedgehogs and prairie
      dogs. The African or Asian hedgehog differs from the larger European hedgehog.
      Pronounced differences in size, seasonal behavior, and natural diet exist. Since
      the prairie dog's increase in popularity in the pet trade, numerous interrelated
      syndromes have been reported, including respiratory disease, obesity, cardiac
      disease, and oral neoplasia. This article describes the routes of administration
      and the common disease syndromes and appropriate therapeutics for each.

PMID- 11228826
TI  - Therapeutics of companion exotic marsupials.
AB  - Exotic marsupials are becoming popular companion pets, yet little pharmacologic
      information is available to the practitioner. Species include sugar gliders
      (Petarus breviceps), South American (Brazilian) short-tailed opossums
      (Monodelphis domestica), brushtail possum or "phalanger" (Trichosurus vulpecula),
      and wallabies: Bennett's (Macropus rufogriseus rufogriseus) and Tammar or Dama
      (Macropus eugenii). Guidelines for logical choices of medications based on
      allometric scaling, gastrointestinal tract anatomy and physiology, and liver
      metabolism are given. An example of scaling and a formulary based on anecdotal,
      published medications are provided.

PMID- 11228827
TI  - Therapeutics for rabbits.
AB  - A variety of pharmacologic agents are currently available to treat house rabbits.
      In many cases, dosages are based on extrapolation from other species or empirical
      data. Dosing in rabbits is further complicated by individual variation. An
      understanding of rabbit physiology and the pharmacology of prescribed medications
      helps ensure that the agents are used as effectively and safely as possible. In
      this article, basic rabbit pharmacobiology is reviewed and techniques for drug
      administration are described. A formulary for house rabbits is provided.

PMID- 11228828
TI  - Pigeon therapeutics.
AB  - This article examines therapeutics for pigeons, discussing their physiology and
      reproduction, housing, and nutrition. The author also looks at ways to prevent
      infection, while discussing treatments for various viral diseases, such as
      paramyxovirus and pigeon herpesvirus, bacterial infections, such as paratyphoid,
      and parasitic diseases. Drug dosages are listed for antibiotics, antifungals,
      antiparasitics, and vaccines.

PMID- 11228829
TI  - Rodent therapeutics.
AB  - Although the number of rodents kept as pets is increasing in the United States,
      much of the veterinary information that is known regarding their care is derived
      from laboratory animal medicine. This article describes individual species
      variation of medication delivery methods and the associated risks of antibiotic
      usage. A comprehensive formulary is also included.

PMID- 11228830
TI  - Amphibian therapeutics.
AB  - The treatment of diseases in amphibians presents unique challenges for the
      clinician. This article describes the basic principles in selecting and
      administering therapeutics, and provides drug dose rates used successfully in
      amphibians. The importance of proper husbandary and hygiene, as it relates to
      amphibian health and medical management of disease, is also emphasized.

PMID- 11228831
TI  - Chelonian therapeutics.
AB  - Chelonian therapeutics, which include the diagnosis and treatment of aquatic
      turtles, semi-aquatic turtles, and tortoises, are discussed. The author looks at
      various methods of treatment and includes treatment protocols, such as crashed
      out turtle and septic turtle protocol. The article also includes a traditional
      drug formulary and an allometric formulary, containing doses derived from
      scaling, scaling plus empiric experience, empiric experience, and serologic
      studies.

PMID- 11228832
TI  - A formulary for lizards, snakes, and crocodilians.
AB  - A formulary of drug dosages for use in lizards, snakes, and crocodilians based
      primarily on a survey of the existing literature is provided. The formulary is
      presented as a series of four tables: antimicrobial drugs; parasiticide drugs;
      anesthetic and analgesic drugs; and miscellaneous drugs. An extensive
      bibliography is included.

PMID- 11228833
TI  - Passerine and softbill therapeutics.
AB  - Passerines (songbirds) and softbills (toucans and mynahs) are increasingly
      presented for veterinary care as pet owners and aviculturists recognize that
      successful medical and surgical treatment can be performed in these often tiny
      patients. Even with an increasing amount of pharmacokinetic data in birds, the
      use of extrapolated drug regimens continues to be a common practice for these
      species. The extrapolation, using allometric scaling from human, mammalian, and
      avian drugs to passeriformes and softbills, is complicated and limited. In this
      article, the choice of the therapeutic approach is discussed. Once the choice for
      a specific drug is made, tables help calculate the dose in milligrams per
      kilocalorie without using complicated formulas.

PMID- 11228834
TI  - Psittacine therapeutics.
AB  - Psittacine therapeutics incorporates a number of clinical parameters. These
      parameters include fluid therapy, nutritional support, blood transfusions, and
      administration of medications. This article highlights the basic therapeutic
      techniques utilized in a veterinary practice that treats psittacine species.
      Considerations on the practical application of these techniques, as it relates to
      patient presentation and owner compliance, are discussed within each section of
      the article.

PMID- 11228835
TI  - Raptor therapeutics.
AB  - Developing a therapeutic plan for raptors can be challenging because the
      veterinarian must take numerous and sometimes conflicting factors into
      consideration. Successful therapy depends on proper management of the raptor
      patient, beginning with its initial presentation and continuing throughout its
      time in captivity. Important considerations concerning medicine and natural
      history peculiar to raptors are addressed. Guidelines for constructing an
      effective therapeutic plan for the treatment of common diseases and conditions
      seen in wild raptors are presented.

PMID- 11228836
TI  - Action-monitoring dysfunction in obsessive-compulsive disorder.
AB  - Evidence suggests that a hyperactive frontal-striatal-thalamic-frontal circuit is
      associated with the symptoms of obsessive-compulsive disorder (OCD), but there is
      little agreement about the function of the exaggerated activity. We report
      electrophysiological evidence suggesting that part of this system monitors events
      and generates error signals when the events conflict with an individual's
      internal standards or goals. Nine individuals with OCD and 9 age-, sex-, and
      education-matched control participants performed a speeded reaction time task.
      The error-related negativity, an event-related brain potential component that
      reflects action-monitoring processes, was enhanced in the individuals with OCD.
      The magnitude of this enhancement correlated with symptom severity. Dipole
      modeling suggested that the locus of the enhancement corresponded to medial
      frontal regions, possibly the anterior cingulate cortex.

PMID- 11228837
TI  - A neural network model of implicit memory for object recognition.
AB  - People name well-known objects shown in pictures more quickly if they have
      studied them previously. The most common interpretation of this priming effect is
      that processing is facilitated by an implicit memory trace in a perceptual
      representation system. We show that object priming can be explained instead as a
      bias in information processing, without recourse to an implicit memory system.
      Assumptions about psychological decision-making processes and bias were added to
      a neural network model for object identification, and the model accounted for
      performance both qualitatively and quantitatively in four object identification
      experiments.

PMID- 11228838
TI  - Grasping visual illusions: no evidence for a dissociation between perception and
      action.
AB  - Neuropsychological studies prompted the theory that the primate visual system
      might be organized into two parallel pathways, one for conscious perception and
      one for guiding action. Supporting evidence in healthy subjects seemed to come
      from a dissociation in visual illusions: In previous studies, the Ebbinghaus (or
      Titchener) illusion deceived perceptual judgments of size, but only marginally
      influenced the size estimates used in grasping. Contrary to those results, the
      findings from the present study show that there is no difference in the sizes of
      the perceptual and grasp illusions if the perceptual and grasping tasks are
      appropriately matched. We show that the differences found previously can be
      accounted for by a hitherto unknown, nonadditive effect in the illusion. We
      conclude that the illusion does not provide evidence for the existence of two
      distinct pathways for perception and action in the visual system.

PMID- 11228839
TI  - False recognition in women reporting recovered memories of sexual abuse.
AB  - False recognition--the mistaken belief that one has previously encountered a
      novel item--was examined in four groups of subjects: women reporting recovered
      memories of childhood sexual abuse, women who believe that they were sexually
      abused as children but who cannot recall this abuse (the "repressed" group),
      women who were sexually abused as children and always remembered the abuse, and
      women with no history of childhood sexual abuse. Subjects were administered a
      Deese/Roediger-McDermott paradigm. The results suggest that the recovered-memory
      group was more prone to false recognition than the other groups. In addition,
      women reporting recovered and repressed memories showed greater reduction in
      false recognition across study trials than did other subjects, perhaps reflecting
      strategic changes in performance.

PMID- 11228840
TI  - Taking perspective in conversation: the role of mutual knowledge in
      comprehension.
AB  - When people interpret language, they can reduce the ambiguity of linguistic
      expressions by using information about perspective: the speaker's, their own, or
      a shared perspective. In order to investigate the mental processes that underlie
      such perspective taking, we tracked people's eye movements while they were
      following instructions to manipulate objects. The eye fixation data in two
      experiments demonstrate that people do not restrict the search for referents to
      mutually known objects. Eye movements indicated that addressees considered
      objects as potential referents even when the speaker could not see those objects,
      requiring addressees to use mutual knowledge to correct their interpretation.
      Thus, people occasionally use an egocentric heuristic when they comprehend. We
      argue that this egocentric heuristic is successful in reducing ambiguity, though
      it could lead to a systematic error.

PMID- 11228841
TI  - Memory distortions develop over time: recollections of the O.J. Simpson trial
      verdict after 15 and 32 months.
AB  - Fifteen or 32 months after the verdict was announced in the O.J. Simpson murder
      trial, we asked college students about how they had heard the news, and we
      compared their responses with what they had told us 3 days after the verdict. Our
      study is the first to have assessed recollective accuracy at two different
      intervals more than 1 year after a noted public event. The quality of the
      recollections after 32 months was strikingly different from the quality of the
      recollections after 15 months. After 15 months, 50% of the recollections were
      highly accurate, and only 11% contained major errors or distortions. After 32
      months, only 29% of the recollections were highly accurate, and more than 40%
      contained major distortions. Retention interval appears to be an important factor
      determining the frequency of memory distortions, and differences in the retention
      interval across studies may account for some of the contradictions in the
      flashbulb-memory literature. Metamemory errors and source memory difficulties are
      a likely basis of poor memory performance after long retention intervals. The
      results highlight the marked qualitative changes in recollections that can occur
      between 1 and 3 years after information has been acquired.

PMID- 11228842
TI  - Neural correlates of theory-of-mind reasoning: an event-related potential study.
AB  - Everyday understanding of human behavior rests on having a theory of mind--the
      ability to relate people's actions to underlying mental states such as beliefs
      and desires. It has been suggested that an impaired theory of mind may lie at the
      heart of psychological disorders that are characterized by deficits in social
      understanding, such as autism. In this study, we employed the event-related
      potential methodology to index the activity of neural systems that are engaged
      during theory-of-mind reasoning in adults. Specifically, neural activity elicited
      by tasks that required thinking about mental as compared with nonmental
      representations (i.e., beliefs vs. photographs) was characterized by a focally
      enhanced positivity over left frontal areas, which was diminished over left
      parietal areas. These findings provide an important perspective on both
      children's theory-of-mind development and the neurobiology of disorders in which
      theory of mind seems to be impaired.

PMID- 11228843
TI  - The angular gyrus in developmental dyslexia: task-specific differences in
      functional connectivity within posterior cortex.
AB  - Converging evidence from neuroimaging studies of developmental dyslexia reveals
      dysfunction at posterior brain regions centered in and around the angular gyrus
      in the left hemisphere. We examined functional connectivity (covariance) between
      the angular gyrus and related occipital and temporal lobe sites, across a series
      of print tasks that systematically varied demands on phonological assembly.
      Results indicate that for dyslexic readers a disruption in functional
      connectivity in the language-dominant left hemisphere is confined to those tasks
      that make explicit demands on assembly. In contrast, on print tasks that do not
      require phonological assembly, functional connectivity is strong for both
      dyslexic and nonimpaired readers. The findings support the view that
      neurobiological anomalies in developmental dyslexia are largely confined to the
      phonological-processing domain. In addition, the findings suggest that right
      hemisphere posterior regions serve a compensatory role in mediating phonological
      performance in dyslexic readers.

PMID- 11228844
TI  - The political psychology of reproductive strategies.
AB  - We argue that several reproductive strategies that parental investment theory
      suggests are adaptive for men and for women are in fact most adaptive for
      individuals able and willing to use power in dominance relationships. We tested
      whether people's support for social dominance mediates their willingness to use
      these reproductive strategies. We hypothesized that the strategies of multiple
      simultaneous mating, resistance to caring for children as one's own, and sexual
      jealousy will be appealing especially to men who approve of social dominance, and
      that finding a high-status, high-earning mate will appeal especially to women who
      approve of social dominance. Support for the hypotheses using multiple samples
      and multiple measures was found, and theoretical issues are discussed.

PMID- 11228845
TI  - Conceptual and motor learning in music performance.
AB  - Are the mental plans for action abstract or specified in terms of the movements
      with which they are produced? We report motor independence for expert music
      performance but not for novice performance in a transfer-of-learning task.
      Skilled adult pianists practiced musical pieces and transferred to new pieces
      with the same or different motor (hand and finger) requirements and conceptual
      (melodic) relations. Greatest transfer in sequence duration was observed when the
      same conceptual relations were retained from training to transfer, regardless of
      motor movements. In a second experiment, novice child pianists performed the same
      task. More experienced child pianists showed transfer on both the motor and the
      conceptual dimensions; the least experienced child pianists demonstrated transfer
      only to sequences with identical motor and conceptual dimensions. These findings
      suggest that mental plans for action become independent of the required movements
      only at advanced skill levels.

PMID- 11228847
TI  - Viewpoint dependence and object discriminability.
AB  - In an attempt to reconcile results of previous studies, several theorists have
      suggested that object recognition performance should range from viewpoint
      invariant to highly viewpoint dependent depending on how easy it is to
      differentiate the objects in a given recognition situation. The present study
      assessed recognition across depth rotations of a single general class of novel
      objects in three contexts that varied in difficulty. In an initial experiment,
      recognition in the context involving the most discriminable object differences
      was viewpoint invariant, but recognition in the least discriminable context and
      recognition in the intermediate context were equally viewpoint dependent. In a
      second experiment, utilizing gray-scale versions of the same stimuli, almost
      identical viewpoint-cost functions were obtained in all three contexts. These
      results suggest that differences in the geometry of stimulus objects, rather than
      task difficulty, lie at the heart of previously discrepant findings.

PMID- 11228846
TI  - The genetics of dietary experience in a restricted natural population.
AB  - The sources of individual differences in human and non-human animals remain
      controversial. We demonstrate that diet and genetics interact in determining the
      ontogenetic trajectory of chemosensory and prey preferences in the common garter
      snake, Thamnophis sirtalis, a dietary generalist. In litters of neonate snakes
      from a single small field in an earthworm-ingesting population, initial responses
      to chemical cues from fish and worm were similar, with zero heritabilities. After
      12 meals on fish, however, the heritability of both fish and worm chemosensory
      responses increased markedly, the change in response to fish but not worm
      chemicals was heritable, the relative preference for fish versus worm was
      heritable, and the change in relative preference was heritable. In addition,
      growth rates on each diet were related to changes in chemoreceptive responses.
      Such genetic-environment variation that emerges only after equivalent ontogenetic
      experience may be a factor in responses to environmental change in many species.

PMID- 11228848
TI  - Twelve-month-old infants interpret action in context.
AB  - Two experiments assessed infants' understanding that actions that occur in
      sequence may be related to an overarching goal. Experiment 1 tested whether
      embedding an ambiguous action (touching the lid of a box) in a sequence that
      culminated with an action infants readily construe as goal-directed (grasping a
      toy inside the box) would alter infants' construal of the ambiguous action.
      Having seen the ambiguous action in this context, infants later construed this
      action in isolation as being directed at the toy within the box. Experiment 2
      tested whether infants related the two actions on the basis of the temporal or
      the causal relation between them. When the causal relation was disrupted but the
      temporal relation was preserved, infants no longer related the two actions. These
      findings indicate that 12-month-old infants relate single actions to overarching
      goals and that they do so by construing goal-directed action in a causal
      framework.

PMID- 11228849
TI  - Distress vocalizations in infant rats: what's all the fuss about?
AB  - Ultrasonic vocalizations emitted by infant rodents are typically characterized as
      cries of distress. There are two contexts that are known to reliably elicit
      ultrasound production: extreme cold exposure and administration of clonidine, an
      alpha 2 adrenoceptor agonist. Noting that these two contexts both entail
      pronounced decreases in cardiac rate, we have hypothesized that the vocalizations
      are acoustic by-products of a physiological maneuver, the abdominal compression
      reaction (ACR), that increases venous return to the heart when return is
      compromised. As a critical test of this hypothesis, we measured venous pressure
      near the right atrium in 15-day-old rats after clonidine administration.
      Consistent with the ACR hypothesis, emission of ultrasound was accompanied by
      large and reliable increases in venous pressure and, therefore, venous return.
      These results provide strong, direct support for the ACR hypothesis and, by doing
      so, underscore the potential pitfalls of anthropomorphic interpretations of the
      vocalizations of infant rats.

PMID- 11228850
TI  - The effect of callosotomy on novel versus familiar bimanual actions: a neural
      dissociation between controlled and automatic processes?
AB  - The corpus collosum is the large band of fibers that connects the two cerebral
      hemispheres of the brain. Individuals who have had the fibers of these tracts
      surgically severed by callosotomy are able to draw two different spatial figures
      simultaneously using the left and right hands, without evidence of interactions
      in the spatial planning processes. Paradoxically, tasks (e.g., tying shoes) that
      appear to depend on spatial interactions between the left and right hands, each
      of which is controlled by a separate cerebral hemisphere, pose little difficulty.
      How can this be? In the study reported here, we observed that well-learned
      cooperative actions of the hands remain intact in 2 callosotomy patients, whereas
      actions novel to these patients are virtually impossible for them to produce
      without visual guidance. We infer that duplicate memory engrams of well-learned
      actions can be accessed by both cerebral hemispheres without callosal mediation,
      whereas callosal interactions are necessary for precise cross-matching of sensory
      information during spatial planning or perceptual-motor learning.

PMID- 11228851
TI  - Unconscious facial reactions to emotional facial expressions.
AB  - Studies reveal that when people are exposed to emotional facial expressions, they
      spontaneously react with distinct facial electromyographic (EMG) reactions in
      emotion-relevant facial muscles. These reactions reflect, in part, a tendency to
      mimic the facial stimuli. We investigated whether corresponding facial reactions
      can be elicited when people are unconsciously exposed to happy and angry facial
      expressions. Through use of the backward-masking technique, the subjects were
      prevented from consciously perceiving 30-ms exposures of happy, neutral, and
      angry target faces, which immediately were followed and masked by neutral faces.
      Despite the fact that exposure to happy and angry faces was unconscious, the
      subjects reacted with distinct facial muscle reactions that corresponded to the
      happy and angry stimulus faces. Our results show that both positive and negative
      emotional reactions can be unconsciously evoked, and particularly that important
      aspects of emotional face-to-face communication can occur on an unconscious
      level.

PMID- 11228852
TI  - Functional changes of ventricular late potentials by provocation with increase of
      heart rate. Evaluation during atrial pacing.
AB  - BACKGROUND: Standard methods fail to reveal late potentials in 20 to 30% of
      patients with ventricular arrhythmias after myocardial infarction. However, these
      patients may develop transient delayed ventricular activation during increases in
      heart rate. METHODS AND RESULTS: Atrial pacing was performed, at the rates of 100
      min-1 and 120 min-1, in 50 patients after myocardial infarction. Twenty-six
      patients had a history of documented, sustained ventricular tachycardia, 12 had a
      history of ventricular fibrillation and 12 no history of ventricular arrhythmias.
      The low-noise surface electrocardiogram was analysed before and during atrial
      pacing in the time and frequency domains. Fifteen of 26 patients with ventricular
      tachycardia, four of 12 with ventricular fibrillation and three of 12 without
      ventricular arrhythmias experienced late potentials during sinus rhythm. Atrial
      pacing led to a shift of 26 +/- 15 ms of preexistent late potentials into the ST
      segment, this being greater in patients with anterior infarctions and to an
      increase in magnitude in patients with inferior infarctions. In patients without
      late potentials during sinus rhythm, atrial pacing provoked late potentials in
      eight of 11 patients with ventricular tachycardia, in four of eight patients with
      ventricular fibrillation and in one of nine patients without ventricular
      arrhythmias. Low amplitude signals (LAS) were increased in patients after
      inferior and filtered QRS in patients after anterior infarction. In 10 patients
      without cardiac disease no late potentials were detectable in the time and
      frequency domain either at rest or during increased heart rate. CONCLUSIONS:
      Increase in heart rate may unmask late potentials in patients prone to malignant
      ventricular arrhythmias. Therefore, functional late potential analysis with non
      invasive clinical stress tests, i.e. exercise tests, should be performed only
      with an adequate rate response. This might identify patients at risk of malignant
      ventricular arrhythmias otherwise not identified with conventional late potential
      analysis.

PMID- 11228853
TI  - Programming a fixed long atrioventricular delay is not effective in preventing
      ventricular pacing in patients with sick sinus syndrome.
AB  - AIM: Most patients with sick sinus syndrome (SSS) and normal atrioventricular
      (AV) conduction receive dual chamber (DDDR) pacemakers. Programming a long AV
      delay has been proposed to avoid ventricular pacing. The present study aimed to
      evaluate ventricular stimulation in SSS patients with DDDR pacemakers with a long
      AV delay. METHODS AND RESULTS: Thirty eight patients treated with DDDR pacemakers
      with a fixed long AV delay (300 ms) were studied. Data from the pacemaker event
      recorder were retrieved after 3 months and every year after implantation. Ten
      patients underwent 24 h Holter recording. Mean follow-up was 11.9 +/- 8.3 months.
      Median daily number of paced events in the ventricle was 2659 (25th-75th
      percentiles: 775-21 315) with a large inter-individual variation. The proportion
      of paced events in the ventricle correlated weakly with the baseline PQ interval
      (Spearman's rho 0.331, P = 0.043). In 12/38 patients the mean daily number of
      paced events in the ventricle exceeded 10,000. During 24 h Holter recording,
      pacemaker arrhythmias caused by repetitive retrograde atrioventricular
      conduction, known as VA (ventriculoatrial) conduction, occurred in five out of 10
      patients. CONCLUSION: DDDR pacing with a fixed long AV delay is inefficient in
      reducing ventricular pacing in one third of patients and is associated with a
      high risk of arrhythmias caused by repetitive retrograde AV conduction, and
      therefore cannot be recommended for general use in SSS patients.

PMID- 11228854
TI  - Cardiac output-based versus empirically programmed AV interval--how different are
      they?
AB  - AIMS: To compare empirically programmed and cardiac output-based programming of
      atrioventricular (AV) interval in patients with dual chamber pacemakers. METHODS
      AND RESULTS: In 19 patients with implanted dual chamber pacemakers due to AV
      block but otherwise normal hearts, cardiac output was assessed using an impedance
      cardiography device. In all patients, the AV interval had been previously
      programmed empirically by an experienced cardiologist. Cardiac output was
      estimated at AV intervals from 50 to 250 ms during VDD pacing. AV intervals
      adjusted by serial cardiac output estimations caused a rise in cardiac output in
      84% of patients. The maximal achievable cardiac output was greater by 12% +/- 8%
      (range 0-32%), P < 0.001, than was observed with empirically programmed AV
      intervals. CONCLUSIONS: In patients with dual chamber pacemakers due to AV block
      and otherwise normal hearts, empirically selected AV intervals may lead to
      compromise of cardiac haemodynamics. Optimal AV intervals may be selected by
      serial cardiac output measurements.

PMID- 11228855
TI  - Determination of the optimal atrioventricular delay in DDD pacing. Comparison
      between echo and peak endocardial acceleration measurements.
AB  - The goal of this study was to compare two methods determining the optimal
      atrioventicular delay (AVD) in 19 patients implanted with the BEST-Living system
      for complete heart block. The definition of the optimal AVD was: the AVD with the
      echo method that provided the longest diastolic filling time without interruption
      of the A wave, and the AVD with the peak endocardial acceleration (PEA) method,
      corresponding to the knee of the PEA curve vs AV delay. The amplitude of the PEA
      was measured for every AVD programmed via an automatic scanner in steps of 60 to
      300 ms (40 ms steps): in the VDD pacing mode with a low base rate, to obtain 100%
      sensed P waves; in DDD with a base rate = sinus rate + 20%, to obtain 100% paced
      P waves. Echocardiographic (Echo) measurement of the left ventricular filling
      time were performed in the same AV delay settings in VDD and DDD as the ones
      tested in the PEA method, which were manually programmed. The optimal AVDs
      obtained in DDD and those obtained in VDD were compared in the echo and the PEA
      tests by a paired Student's t-test. The optimal AVDs obtained by both Echo and by
      PEA were also compared by a paired Student's t-test in VDD and DDD. The r value
      of the correlation between the optimal AVDs obtained by Echo and those obtained
      by PEA was calculated. Similar values of optimal AVD were obtained with both
      methods. The optimal AVDs given by the Echo technique (179 +/- 25 ms in DDD and
      124 +/- 18 ms in VDD) were slightly, but significantly shorter than the ones
      obtained with the PEA method (202 +/- 21 ms in DDD and 145 +/- 18 ms in VDD, P <
      0.05). A highly significant difference between AVD VDD and AVD DDD was found with
      both methods (P < 0.001). The correlation between the AVDs obtained with the echo
      and the PEA methods was highly significant (r = 0.78, P < 0.01). Pacemaker
      software could be modified to determine automatically the optimal AVDs to be
      applied throughout the heart rate range.

PMID- 11228856
TI  - Placement of atrial pacing leads during atrial fibrillation. Feasibility and
      subsequent lead performance.
AB  - AIMS: To assess the feasibility of placing permanent atrial pacing leads during
      atrial fibrillation (AF) and whether such leads function satisfactorily. METHODS
      AND RESULTS: Prospective study of 17 consecutive patients in whom permanent
      atrial leads were positioned during an episode of paroxysmal AF. Fluoroscopic
      position ('figure of 8' or side-to-side movement and anterior position in RAO
      projection), lead impedance (> 300 but < 1000 ohms) and intracardiac electrogram
      (average peak to peak amplitude > 1 mV) were used to define an acceptable lead
      position. At 8 weeks post implant we measured: pulse duration pacing threshold at
      5 V; lead impedance at 5 V and 0.5 ms; intracardiac electrogram (EGM) signal
      amplitude. At the end of the study we reviewed patients to establish whether AF
      had become permanent. In all patients, follow-up demonstrated satisfactory lead
      function. All leads had impedances between 300 and 1000 ohms. Pacing thresholds
      were all < 0.1 ms at 5 V. Mean atrial EGM amplitude seen in sinus rhythm was 3.3
      mV (range 1.2-8.4); in patients where all follow-up was in AF in was 2.1 mV
      (range 1.5-2.5). Nine patients (53%) developed permanent AF. CONCLUSION: Placing
      atrial leads during AF is feasible using the technique described. However, some
      patients progress to chronic AF, eliminating the benefits of atrial pacing.

PMID- 11228857
TI  - Bipolar atrial sensing thresholds in sinus rhythm and atrial tachyarrhythmias. A
      comparative analysis in patients with DDDR pacemakers.
AB  - Automatic mode switching (AMS) function in dual chamber pacemakers depends on
      adequate detection of atrial tachyarrhythmias. There are few data on showing how
      intra-operative atrial signal amplititude during sinus rhythm can predict atrial
      tachyarrhythmias after pacemaker implantation. In 43 patients undergoing DDDR
      pacemaker implantation and atrioventricular nodal ablation for the treatment of
      drug-refractory paroxysmal atrial fibrillation, atrial sensing thresholds during
      sinus rhythm and during induced atrial tachyarrhythmias (24-48 h after device
      implantation) were analysed. Five different DDDR pacemaker systems were implanted
      (Chorus 7034, Ela Medical n = 13; Meta DDDR 1254, Telectronics Pacing Systems n =
      12; Vigor DR 1230, Guidant n = 6; Trilogy DR 2364, Pacesetter, n = 2; Kappa DR
      401, Medtronic USA n = 10). Every patient received a steroid-eluting, screwing,
      bipolar atrial lead (Medtronic, Capsure-Fix 4068). The mean P wave amplitude
      during implantation was 3.91 +/- 1.14 mV. The mean atrial sensing threshold
      during sinus rhythm and during all modes of induced atrial tachyarrhythmias was
      3.35 +/- 1.0 mV, and 1.52 +/- 0.92 mV, respectively (P < 0.001). Atrial
      fibrillation was induced in 36 patients. The mean sensing threshold during sinus
      rhythm in this patient group was 3.39 +/- 1.01 mV, the mean sensing threshold
      during atrial fibrillation was 1.27 +/- 0.56 mV, reflecting a 63% reduction of
      sensing threshold compared with sinus rhythm (P < 0.001). Atrial flutter was
      induced in seven patients. The mean sensing threshold during sinus rhythm was
      2.92 +/- 1.19 mV, the mean sensing threshold during atrial flutter was 2.79 +/-
      1.26 mV, reflecting a reduction of 5% (ns) compared with sinus rhythm. Atrial
      sensing thresholds during sinus rhythm were significantly correlated with sensing
      thresholds during atrial tachyarrhythmias (r = 0.44; P < 0.002), but there were
      significant variations in intra-individual results. The reduction of atrial
      sensing thresholds between sinus rhythm and induced atrial tachyarrhythmias
      ranged from 30% to 82%. CONCLUSION: Bipolar atrial sensing thresholds during
      sinus rhythm are correlated with sensing thresholds during atrial
      tachyarrhythmias, but there is a large degree of variance in individual patients.
      A 4:1 to 5:1 atrial sensing safety margin based on sensing threshold during sinus
      rhythm is a predictor for adequate postoperative detection of atrial
      tachyarrhythmias and the function of AMS devices.

PMID- 11228858
TI  - Is a pacemaker indicated for vasovagal patients with severe cardioinhibitory
      reflex as identified by the ATP test? A preliminary randomized trial.
AB  - BACKGROUND: A previous observational study suggested that, in syncopal elderly
      patients with vasovagal syndrome, a test using adenosine-5'-triphosphate
      (intravenous ATP 20 mg. 2 ml-1) could identify a subgroup of patients at high
      risk of severe cardioinhibitory response and guide the therapeutic strategy. To
      test one aspect of these results prospectively, we designed a small study
      focusing only on vasovagal patients with abnormal response to ATP testing.
      METHODS: Twenty patients hospitalized for syncope, which was considered to be
      vasovagal, and exhibiting an abnormal ATP test--defined by a longer than 10 s
      cardiac pause--were randomized to two groups: half to implantation with a dual
      chamber pacemaker and half to usual medical care. All patients who were not
      hospitalized for recurrences were assessed every 6 months in the clinic or by
      telephone. RESULTS: At baseline, the randomized patient groups were similar in
      their demographic and health characteristics and in the results of their ATP
      tests, for example the mean cardiac pause (21.4 +/- 9.3 vs 15.9 +/- 3.7 s) and
      the mean interval between escape beats during the pause (7.29 +/- 4.2 vs 7.48 +/-
      3.3 s). During a mean follow-up of 52 months, recurrences appeared in six of the
      10 usual-care patients (range 0.2-29 months) but in none of the implanted
      patients (P < 0.02). CONCLUSIONS: This limited trial (1) supports the conclusion
      that patients with an abnormal ATP test who receive a dual-chamber pacemaker
      suffer fewer recurrences than those who are monitored only; and (2) consequently
      further supports the hypothesis that, among vasovagal patients, a cardiac pause
      of longer than 10 s in patients administered ATP identifies those at high risk of
      symptomatic vagal cardiac inhibition.

PMID- 11228859
TI  - Pacing-induced left ventricular dysfunction. Relationship with coronary
      perfusion.
AB  - In a patient admitted with symptomatic complete heart block, a DDD pacemaker was
      implanted. Prior to implantation, echocardiography showed normal left ventricular
      function. Shortly after implantation, acute congestive heart failure developed
      with extensive regional hypo- and akinetic segments in the anteroseptal,
      anterolateral and apical region. Subsequent perfusion imaging with
      methoxyisobuticeisonitrite (MIBI) at rest demonstrated hypoperfusion in the same
      regions while coronary angiography showed normal epicardial coronary vessels.
      Thus, impaired regional coronary flow can be associated with cardiac stimulation,
      inducing marked deterioration of left ventricular function.

PMID- 11228860
TI  - The clinical value of QT dispersion: new perspectives on the assessment of
      cardiac repolarization more than 75 years after Bazett's formula.

PMID- 11228861
TI  - Electrophysiological profile after inward rectifier K channel blockade by barium
      in isolated rabbit hearts. Altered repolarization and unmasked decremental
      conduction property.
AB  - AIMS: The aims of this study were to define the changes of cardiac conduction
      properties after selective IK1 blockade in isolated hearts. METHODS AND RESULTS:
      Intracardiac recording and stimulation in Langendorff-perfused rabbit hearts were
      used to define cardiac conduction properties after Ba2+, a well known IK1
      blocker. Ba2+ prolonged the corrected QT interval and decreased, or even
      abolished, the amplitude of the T wave. The conduction time through the
      sinoatrial (SA interval), the atrioventricular node (AH interval) and His
      Purkinje system (HV interval) were not significantly changed. However, at higher
      atrial pacing rates the HV interval was lengthened by Ba2+ in a frequency
      dependent manner. The recovery curve of the His-Purkinje system (the relationship
      of H2V2 to V1H2) was changed by Ba2+ to a prematurity-dependent pattern (AV nodal
      behaviour). Such a response was neither observed with 4-aminopyridine (Ito
      blocker) nor with d-sotalol (IK blocker). The atrial and ventricular refractory
      periods as well as the relative refractoriness (measured by the difference
      between relative refractory period and the absolute refractory period) of the
      ventricular tissue were increased by Ba2+. CONCLUSION: The electrophysiological
      profile of selective IK1 block in isolated hearts revealed altered repolarization
      of cardiac tissue. The decremental conduction properties, which are normally
      present in the atrioventricular node (with a paucity of IK1), were unmasked by
      IK1 block in the His-Purkinje system. The T wave, particularly its amplitude, is
      more closely related to IK1 than to Ito.

PMID- 11228862
TI  - Myers-Briggs type and medical specialty choice: a new look at an old question.
AB  - BACKGROUND: Career development of health professionals is one of many uses of
      Myers-Briggs Type Indicator (MBTI), with many studies reported from the 1950s.
      Since 1977, no large-scale effort to collect data on the medical school
      population has been reported. PURPOSE: To determine (a) changes in MBTI profiles
      of medical students over time, (b) differences between the profiles of men and
      women and the effects of the increased number of women in medical school, (c)
      possible associations between type and career choices, and (d) possible type
      differences of graduates selecting primary care and specialties. METHOD: Twelve
      U.S. schools with data on 3,987 students contributed to a database of their
      graduates' MBTI type and specialty choice at Match. RESULTS: Compared with data
      from the 1950s, the type distribution of physicians has remained fairly stable,
      save for a trend toward more judging types. Women in medicine today are more
      representative of the general population on the feeling dimension than earlier,
      when medicine was more male-dominated. Women are more likely than men to choose
      primary care specialties, as are those with preference for introversion and
      feeling. Feeling types choose Family Medicine significantly more often than
      thinking types; male, extraverted, and thinking types choose surgical
      specialties. Of those selecting nonprimary care, male, extraverted, and thinking
      types choose surgical specialties significantly more than women, introverted, and
      feeling types. CONCLUSION: Type remains useful for understanding how some aspects
      of personality relate to medical specialty choice.

PMID- 11228863
TI  - An encounter-based analysis of the nature of teaching and learning in a 3rd-year
      medical school clerkship.
AB  - BACKGROUND: Much of medical education has shifted from the hospital to ambulatory
      settings where each student works with a preceptor. PURPOSE: Our objectives were
      to describe the nature of community-based learning and to explore how learning
      experiences vary by type of health care visit. METHODS: This prospective study
      used both paper- and computer-based documentation systems to collect information
      on student-patient-preceptor encounters. A consecutive sample of 3rd-year medical
      students contributed data on 1 full clinical day each week as they rotated
      through a required 8-week family medicine clerkship. The main measures of
      interest included patient age, gender, health care visit type (acute, acute
      exacerbation of chronic, chronic, and health maintenance), method of learning in
      history taking and physical examinations (observing preceptor, being observed by
      preceptor, performing unobserved, or working jointly with preceptor), content of
      physical examinations, amount of preceptor feedback, and preceptor teaching
      content. RESULTS: Sixty-three students contributed data on 4,083 patient
      encounters. The majority of visits concerned acute complaints (37.7%) or health
      maintenance (26.4%). Many encounters involved students conducting the
      cardiovascular and pulmonary exams (33.2% each); fewer encounters involved
      neurologic (6.9%), gynecological (4.5%), and genitourinary (2.2%) exams. Students
      reported being observed performing histories and physical exams in 4% and 6% of
      encounters respectively. The most common student experiences were performing
      histories and performing physical exams unobserved during acute visits, which
      accounted for 65.8% and 52.4% of encounters overall. CONCLUSIONS: This system is
      useful for determining educational content and processes that occur in ambulatory
      settings. Important differences were found in teaching and learning by type of
      health care visit. This factor can and should be used when considering how
      students meet educational objectives in community-based ambulatory settings.

PMID- 11228864
TI  - Humanism: is its evaluation captured in commonly used performance measures?
AB  - BACKGROUND: There is an increased awareness of the importance of humanistic
      behavior and its education in the medical school curriculum. Relatively little is
      known about correlations between humanism and other performance measures.
      PURPOSES: To determine the correlation between humanism and other commonly used
      performance measures, and to determine if more humanistic students perform
      better, the same, or worse than less humanistic students. METHODS: During the
      Family Medicine clerkship, standardized patients (SPs) used the Physician
      Humanism Scale to assess 428 students for humanism. Clinical preceptors, SPs,
      written assignments, and a national knowledge examination also assessed student
      performance. The humanism scores were correlated with the SP and non-SP
      performance measures. RESULTS: Humanism scores were significantly and positively
      correlated to all of the performance measures, but the correlation coefficients
      were low, ranging from .12 to .31. Students in the lowest quartile for humanism
      consistently scored lower for all of the performance measures, including both
      local and national exams (two-tailed significance < .018). Students with very low
      humanism scores still passed other performance evaluations. CONCLUSIONS: The
      correlation between humanism and other performance measures is quite low,
      indicating that a separate measure for humanism provides different and additional
      information that current performance measures do not include. More humanistic
      students perform better than their less humanistic peers, but current performance
      measures do not identify students with the lowest scores on humanistic behavior.
      This study supports the inclusion of humanism as an additional, independent
      performance measure.

PMID- 11228865
TI  - Minority students, affirmative action, and the admission process: a literature
      review, 1987-1998.
AB  - BACKGROUND: Despite numerous initiatives, medical educators have failed to effect
      a sustainable increase in the number of underrepresented minority students at
      medical colleges in the United States. This study reviewed the recent literature
      regarding the admission process to specifically examine and determine if current
      policies are helping facilitate the proper representation of minority students.
      Papers were selected on the basis of their relevance to the topic of
      underrepresented minority students and medical school admission policies and were
      limited to the years between 1987 and 1998. Each paper was individually evaluated
      on the basis of its study design and soundness of its contribution to the field.
      SUMMARY: The articles are organized under 4 major themes: Cognitive factors
      (mostly Medical College Admission Test scores and grade point average),
      noncognitive factors (e.g., leadership ability, interpersonal skills,
      motivation), the admission interview, and enrichment programs. Table 1 briefly
      summarizes these constituent articles. CONCLUSION: It was found that the body of
      literature is inadequately small and heterogeneous with regard to study design
      and results. A concerted effort must be made across medical education to correct
      the deficiencies in this particular area.

PMID- 11228866
TI  - Prediction accuracy and financial savings of four screening tests for a
      sequential test of clinical performance.
AB  - BACKGROUND: Sequential testing of clinical performance is an effective strategy
      to reduce cost of testing. PURPOSE: To evaluate prediction accuracy and financial
      savings of 4 screening tests of clinical performance. METHODS: Screening tests
      were created from a 13-case examination taken by 434 medical students at 4
      schools. Regression analysis determined prediction accuracy for 2 test outcomes.
      Financial savings were computed from published estimates. RESULTS: Zero false
      passes were obtained with the "Total Number of Cases Passed" screening test, but
      it saved only 27%. Sixty-two percent savings with 5% false passes occurred with
      the "Classification" screening test. The "Scale" and "Mini Test" screening tests
      would have excused 79% and 67% examinees with 5% and 1% false passes,
      respectively. CONCLUSIONS: Prediction accuracy varies with screening test and
      outcome measure. Sequential testing of clinical performance can save 40% to 60%
      with low false pass rates. However, programs need to consider loss of information
      for curriculum and individual feedback relative to financial savings.

PMID- 11228867
TI  - Qualitative assessment of the impact of health care reform on the availability of
      clinicians for preclinical medical instruction.
AB  - PURPOSE: Over the past 5 years, Calgary clinicians experienced the restructuring
      of health care delivery and a move to a presentation-based curriculum at the
      University of Calgary. Course coordinators have noted increased difficulty in
      recruiting clinical lecturers at the preclinical undergraduate level. This study
      was designed to evaluate the relative importance of factors that may influence
      the time clinicians spend teaching at this level. SUMMARY: This descriptive
      survey was conducted within the University of Calgary, Faculty of Medicine, a
      teaching institution affiliated with the Calgary Regional Health Authority, which
      is responsible for the delivery of health care within the City of Calgary. Basic
      scientists, residents, and adjunct medical professionals were excluded from a
      list of lecturers for the academic year 1996-97, leaving a target population of
      386. Respondents were stratified according to university appointment, specialty,
      type of medical training, and hours taught in the 1996-97 academic year.
      Dependent variables included the financial constraints, time constraints, health
      care reform, changes in the undergraduate medical education curriculum, and lack
      of recognition on availability for teaching. Written comments were also
      categorized and analyzed according to the same variables. A response rate of 79%
      (n = 305) was achieved. Of the respondents, 52% agreed that recent reform has
      made it more difficult to teach; full-time faculty were less likely to agree
      compared to non-full-time faculty (60% vs. 44%; nonparametric median test, chi 2
      = 6.18, p = .046). Twice as many family physicians reported that financial
      constraint was a factor (66%) when compared to other specialists, whereas
      relatively few full-time faculty noted it to be a concern (12%) when compared to
      major part-time (43%) and non-full-time/major part-time appointees (66%; chi 2 =
      23.4, p < .0001). Clinicians reporting the most teaching hours (more than 30)
      were most likely to describe an increase in teaching hours (61%). Nonfaculty
      members were less aware of the recent curricular changes (73%); however, more
      family physicians felt that these changes had a positive impact on willingness to
      teach (10%) compared to surgical (8%) and nonsurgical specialists (9%; chi 2 =
      6.07, p = .048). Forty-five percent of respondents agreed that they would be more
      willing to teach if offered some from of recognition. Two thirds of written
      comments suggested that recognition should be nonmonetary (e.g., faculty
      promotion, acknowledgment). CONCLUSIONS: The experience at the University of
      Calgary suggests that availability of teachers for preclinical undergraduate
      medical education has diminished as a result of health care reform. Family
      physicians have been affected the most, and the clinical environment will make it
      even more difficult to involve this important group of teachers in undergraduate
      medical education.

PMID- 11228868
TI  - Teaching faculty to conduct problem-based learning.
AB  - PURPOSE: This article is aimed at those who undertake a transition to problem
      based learning (PBL) and focuses on 3 questions that seem most pertinent to the
      effort: (a) what is known from past research about training faculty in the skills
      of PBL?, (b) what skills are important to teach faculty and how does one teach
      them?, and (c) what options are available for training faculty in PBL? SUMMARY:
      The success of any PBL curricular initiative requires the assistance of faculty
      skilled in PBL. The development of faculty with such skills must be a primary and
      ongoing concern of programs or schools launching such efforts. This article
      describes the research associated with training faculty to conduct PBL, the
      skills to be taught, and the training options available. CONCLUSIONS: Few studies
      document the impact of PBL faculty development strategies. Many faculty
      experience a difficult transition when retraining to PBL. Training faculty for
      PBL is often taken to mean training them to be tutors, but there are more skills
      involved in implementing PBL. Finally, there is an implied sequence to training
      faculty to implement PBL.

PMID- 11228869
TI  - Digging the genome for diabetes mellitus: the 2nd ADA Research Symposium on the
      Genetics of Diabetes, San Jose, CA, USA, 17-19 October 1999.
AB  - The diabetes genetics community recently met in California to discuss the impact
      that the latest findings in susceptibility mapping might have on our
      understanding of the pathophysiology of diabetes mellitus and its long-term
      complications. Organized by Ralph DeFronzo (San Antonio, TX) and Alan Permutt (St
      Louis, MO) the symposium covered the genetics of type 1 and type 2 diabetes,
      obesity, approaches to population selection and stratification, quantitative
      trait analysis, epidemiological tools and technological advances in genotyping.

PMID- 11228870
TI  - Still more questions than answers: report on the 5th International Symposium on
      Insulin-like Growth Factors, Brighton, UK, 31 October-4 November 1999.
AB  - The diverse backgrounds of the 550 scientists attending the 5th International
      Symposium on IGFs reflected the increasingly multidisciplinary approach to the
      field of insulin-like growth factor research. The presentations covered every
      aspect of the regulation, structure, physiology and pathology of not only IGF-I
      and IGF-II, but also their cell receptors and intracellular-signalling
      components, their specific-binding proteins (IGFBPs), as well as factors that
      bind to or modify these IGFBPs.

PMID- 11228871
TI  - [Instruments for quantitative methods of nursing research].
AB  - Instruments for quantitative nursing research are a mean to objectify and measure
      a variable or a phenomenon in the scientific research. There are direct
      instruments to measure concrete variables and indirect instruments to measure
      abstract concepts (Burns, Grove, 1997). Indirect instruments measure the
      attributes by which a concept is made of. Furthermore, there are instruments for
      physiologic variables (e.g. for the weight), observational instruments (Check
      lists e Rating Scales), interviews, questionnaires, diaries and the scales (Check
      lists, Rating Scales, Likert Scales, Semantic Differential Scales e Visual
      Anologue Scales). The choice to select an instrument or another one depends on
      the research question and design. Instruments research are very useful in
      research both to describe the variables and to see statistical significant
      relationships. Very carefully should be their use in the clinical practice for
      diagnostic assessment.

PMID- 11228872
TI  - [Motivation and expectations of graduate nursing students at the university of
      Padova].
AB  - The correct planning of a educational university process requires the knowledge
      of students' motivations, aspirations and socio-cultural profile. The aim of this
      study is to describe the students of University of Padua Nursing school recently
      enrolled during the academic year 1998/99, focusing on the motivations of their
      choice and the expectations on the university course. The data were collected
      through a questionnaire on 50 different questions concerning: age, sex, address,
      previous school experience, professional aspirations, problems in learning and
      following the course of the study, influence of advertising in choosing the
      school, ideal and concept of the role of nurse, expectation on the University
      course, knowledge on the didactic plan and future job availability. The study
      investigated 195 (84 from Padua, 54 from Treviso and 49 from Feltre, side
      branches) students. Out of 195 tests, 85.5% were females averaging 21.1 years and
      14.4 were males averaging 22.5 years. Mean high school degree score was 42.8
      (valid score from 36 to 60). 50.6% of the students are resident in the school
      site (main site or side branches) of the school. 85.5% of the students are living
      with theirs parents. The choice of the school was principally due to: future job
      availability (95%), humanitarian reasons (94%), scientific interest (87%), social
      consideration (85%). The study activities were the students' most frequent
      expected difficulty. The choose of the course of study was influenced by: parents
      suggestion (39%), friends suggestion (28%), advertisement and conferences in the
      high school (21%), papers (18%). Very important factor was found previous
      voluntary sanitary experiences.

PMID- 11228873
TI  - [A guide to writing and publishing a research article].
AB  - It is very difficult to write and have own research articles published if there
      is nothing new to say, if what is written is not stated in a coomprehensive way
      or if the editorial notes are not strictely followed. The aim of the article is
      to sustain and encourage first time authors with a guideline to submit their
      articles. Phases of a research process are compared with the sections of the
      article providing the explanation of related contents through some practical
      advices. As an exsample for future Authors, the research article evaluation form
      used by this journal is reported.

PMID- 11228874
TI  - [Religious diversity in hospitals: an aspect to be considered?].
AB  - A study was undertaken among 132 nurses in two religions and two public hospitals
      on religious needs among patients from oriental countries. Aim of the research
      was to investigate the religious needs, among patients generally and
      particularly, among oriental religions and how nurses and hospital
      administrations are considering those needs. From the results it was evidenced
      that nurses in religious hospital paid more attention, to patients needs, than
      those in public hospital. Both groups of nurses seemed to pay little attention
      concerning liturgy, during hospitalization and especially when caring for a
      patient that is dying. A recommendation is therefore to adapt nursing care plan
      including "religion" and besides to prepare information supports with details on
      practices and living conditions regarding major oriental religions existing in
      Italy.

PMID- 11228875
TI  - [Home care service integrated into community nursing service in milan: 5 years of
      experience].
AB  - In Italy the "Elderly Objective Project"--approved with a special resolution of
      Chamber and Senate in January 1992 out of the National Health Plan"--placed the
      domiciliary assistance within a network of territorial services, with the purpose
      to answer to the elderly needs, in social-welfare and health, in their own home
      context, looking over to avoid unnecessary admissions in hospital and promote
      early admissions. The achievement of these directions of these directions have
      created a kind of services which shows an extreme heterogeneity in organization,
      typology and intensity of service delivered, as well as in the monitoring
      strategy, beside the estimation of efficiency and quality of interventions. To
      contribute to knowledge and progress of efficacy interventions for domiciliary
      cares, the author suggests a descriptive analysis of domiciliar assistance,
      existing since 1993 in the USSL 41 of Milan, and a consideration, from a nursing
      pont of view, about the collected data.

PMID- 11228876
TI  - [Alzheimer's disease: factors affecting caregivers' workload].
AB  - The aim of this study was to investigate which factors could play a role on the
      work-load of the Alzheimer patients' caregivers. The work-load was measured by
      means of Zarit's scale and inserted as dependent variable in a regression model,
      where the following independent variables were considered: education and MMSE of
      patients, age, sex of both patients and caregivers. The relevant factors resulted
      patient's age and MMSE, being significantly (p < 0.05) inversely associated with
      work-load. This score reached his maximum when patient's MMSE ranged between 14
      and 16 (medium impairment). However, a large variability was found in this
      interval, suggesting a possible effect of other factors. In addition, we observed
      a decrement of work-load when patients were older, being higher at 50 and lower
      after 72. This effect might be explained by the significant change (especially in
      terms of social and familial life) due to the illness when the patient is
      relatively young. When the patient is older, Alzheimer' disease had smaller
      effect on the caregiver's work-load.

PMID- 11228877
TI  - [The DIALYSIS AMICA project].
AB  - The denominated Plan "DIALYSIS FRIEND" organized in the region March in the 1998,
      has seen involved almost all the centers of Dialysis of the region. He has the
      purpose of furnish the sanitary operators the tools for face the varied strife
      torn situations in first person and emotional that they present themselves in an
      U.O. to "high tension" like result be the Dialysis and the "particularity"
      personality of whom affection from chronic uraemia comes subjected to dialysis.
      Besides through the identification of a "profile of fitness" furnishes data on
      the compliance of the person dialyzed or in pre-dialysis to the different
      techniques of dialysis. The share of the doctor, of a chief ward, and of any
      nurses of the U.O. of Nefro/Dialysis of Fano to such plan has resulted to be a
      very significance experience. The participants to the course tell their
      experience.

PMID- 11228878
TI  - [Job safety: where there is high tension at the work place: MOBBING].
AB  - In this article appears the particular phenomenon called MOBBING which begins to
      came out even in our job places, after years long researches and foreign studies.
      This syndrome, besides stress and burn-out, it's one of the working risk factors
      of organizational-psychological kind. The word Mobbing comes from the ethological
      vocabulary and it means the attack of some part of a crowd against the most weak
      member. It can be interesting to sketch some not-minority problems that are
      connected with job healthiness doing confusion as it would only be individuals
      problems.

PMID- 11228880
TI  - [The shortage of nurses in the member states of the European Union].

PMID- 11228879
TI  - [Research on the biological risk in the hospital environment].
AB  - The epidemiological monitoring of injuries due to exposure to potentially
      infected biological liquids constitutes the indispensable premise for the
      elaboration of strategies meant to intervene to reduce the incidence. This work
      shows the results of an epidemiological study relative to the period going from
      January 1, 1994--December 31, 1998 elaborated by the use of the register of
      injuries deposited with the Sanitary Direction. The variables shown here allowed
      us to individualize the prevalence of injuries in the various professional
      categories, the working zones, the type and form of injury, the use of individual
      protection devices. The analyses of the data has shown a scarce sense of risk by
      the sanitary workers and a scarce application of protective measures. It's
      evident of the need to intervene in the formation of the workers to sensibilize
      then to the importance of preventive measures.

PMID- 11228881
TI  - Male contraception: views to the 21st century, Bethesda, MD, USA, 9-10 September
      1999.
AB  - For men who still wish to father children, the contraceptive options currently
      available are withdrawal and the condom. Although significant progress has been
      made on hormonal and vaccine-related approaches to male contraception, a marketed
      product is, at best, several years away. Therefore, the National Institute of
      Child Health and Human Development convened a workshop to discuss novel
      strategies for development of male contraceptives that focused on the testis and
      epididymis. Participants recognized that exploration of these new approaches will
      necessitate considerable investment of funds and research efforts.

PMID- 11228882
TI  - Sex is all in the brain: report of a Novartis Foundation Symposium on the
      Neuronal and Cognitive Effects of Oestrogens, London, UK, 7-9 September 1999.
AB  - Suspicions of the impact of oestrogen beyond its traditional role in sex
      maturation were confirmed with the discovery of oestrogen receptors in a great
      variety of tissues other than just in sex organs. Recently, research findings
      have indicated the central nervous system as one of the prime target organs--not
      only does oestrogen modulate the production and actions of serotonin,
      acetylcholine, dopamine and norepinephrine, but it also encourages the growth of
      new synapses and enhances neuronal survival. Whether the many effects of
      oestrogen operate through classical oestrogen receptors or alternative channels
      remains under intense investigation. During this three-day symposium, researchers
      and clinicians discussed a wide-range of oestrogen-related subjects from novel
      mechanisms of action to the influence of oestrogen on cognition and behaviour,
      and results from clinical studies that suggest oestrogen therapy after menopause
      may protect from Alzheimer's disease.

PMID- 11228883
TI  - Report on the American Society for Bone and Mineral Research Annual Scientific
      Meeting, St Louis, MO, USA, 30 September-4 October 1999.
AB  - The 21st Annual Scientific Meeting of the American Society for Bone and Mineral
      Research (ASBMR) attracted more than 4000 participants to its program of 1600
      submitted papers together with six plenary lectures and the Gerald Aurbach
      Memorial Lecture. Discoveries that had occurred in the field in the last one or
      two years were certainly very much in evidence and dictated the more obvious
      themes.

PMID- 11228884
TI  - Drugs affecting the respiratory system.
AB  - Differences in the disposition of drugs among exotic animals is a well-recognized
      hurdle when treating disease. Differences exist in pharmacokinetics,
      pharmacodynamics, and disease processes. This article focuses on the principles
      of treating respiratory tract diseases, with the recognition that not all drugs
      are indicated for use in all exotic species. The discussion begins with a
      description of respiratory physiology as it pertains to response to drugs, using
      the mammalian lung as a template. The role of respiratory defense mechanisms in
      airway protection and disease is addressed. Drugs used to treat the respiratory
      tract include the bronchodilators and anti-inflammatory drugs, drugs that modify
      respiratory secretions (e.g., mucolytics, mucokinetics, and expectorants),
      antitussive drugs, and decongestants. Aerosolization is an important adjuvant for
      respiratory therapy as long as precautions are met. Infectious diseases are among
      the more common respiratory diseases encountered, and the discussion includes a
      focus on the use of antibiotics for treating respiratory tract infections.

PMID- 11228885
TI  - Respiratory medicine in pigeons.
AB  - This article covers the factors causing respiratory disease in pigeons. The major
      infectious agents are discussed in detail. Clinical signs, diagnosis, prevention,
      and treatment recommendations for the most commonly found pathogens are included.
      Husbandry recommendations are also covered.

PMID- 11228886
TI  - Respiratory diseases of gallinaceous birds.
AB  - Respiratory conditions constitute many of the diseases affecting all avian
      species, including gallinaceous birds. Clinical signs and gross lesions of
      different respiratory diseases are often similar, and establishing a definitive
      diagnosis may require ancillary laboratory testing. Determination of a specific
      diagnosis allows practitioners to select the most effective therapies and to
      prescribe a management program that prevents recurrence.

PMID- 11228887
TI  - Respiratory medicine of cage and aviary birds.
AB  - Respiratory diseases are a relatively common cause of illness and death in cage
      birds. A diagnostic algorithm is provided based on history, physical examination,
      and ancillary diagnostic findings that assist clinicians in determining the cause
      of a bird's respiratory disease. Also included are detailed descriptions of the
      common respiratory diseases of cage birds and their treatment.

PMID- 11228888
TI  - Ferret respiratory diseases.
AB  - Ferret behavior often brings them into close contact with potential respiratory
      pathogens and traumatic insults. Although respiratory disease accounts for a
      small percentage of cases, they are usually dramatic. Acute and chronic
      conditions occur, and many lesions are confined to the upper or lower respiratory
      tree but may not involve both. Pathogens such as influenza A account for a large
      percentage of upper respiratory infections and often mirror the "flu" season of
      humans. Traumatic insults to the head and chest are relatively common and account
      for many veterinary visits. Numerous diseases affecting the upper and lower
      respiratory systems are discussed, with suggestions for diagnostics and
      therapies.

PMID- 11228889
TI  - Respiratory diseases of rabbits.
AB  - Respiratory diseases are second only to gastroenteric diseases in importance in
      rabbits. Pasteurellosis is the primary respiratory disease affecting domestic
      rabbits, but other bacteria (e.g., Bordetella broniseptica and Staphylococcus
      spp) are significant opportunistic pathogens. The primary manifestations are
      upper respiratory disease (e.g., rhinitis, sinusitis, conjunctivitis, and
      dacryocystitis). Various antimicrobials are effective for treatment.

PMID- 11228890
TI  - Respiratory diseases of rodents.
AB  - Practitioners may be called on to treat rodents with respiratory diseases or to
      advise clients concerning the care of these rodents. Respiratory diseases of
      mice, rats, guinea pigs, and Syrian hamsters are well known because of the use of
      these species in research, whereas few or no reports of respiratory disease in
      rodents of other species exist. Features of the respiratory diseases of these
      four commonly encountered species are reviewed, including causes; clinical signs;
      diagnostic procedures; preventive measures; and, where appropriate, therapies.

PMID- 11228891
TI  - Respiratory diseases, diagnostics, and treatment of marsupials.
AB  - Primary respiratory disease is uncommon in marsupials, but generalized disease
      often involves the respiratory tract in these animals. Other disease entities may
      spread to involve the respiratory system secondarily. Treatment is challenging
      because most animals are severely compromised on presentation. Bacteria, viruses,
      parasites, fungi and yeasts, trauma, and neoplasia all can affect the respiratory
      systems of marsupials. Some of these conditions are only incidental findings,
      whereas others are pathogenic. Many therapies and diagnostic procedures are
      extrapolated from those in companion animal medicine and surgery. Despite the
      problems associated with the diagnosis and treatment of respiratory disease in
      marsupials, new therapeutic agents and diagnostic techniques are making these
      tasks easier and ultimately more successful.

PMID- 11228892
TI  - Obstructive respiratory disease in prairie dogs with odontomas.
AB  - The clinical manifestations of odontomas in prairie dogs are described.
      Familiarity with this disease is important because it is common, and the signs of
      this disease mimic other respiratory disorders.

PMID- 11228893
TI  - Respiratory diseases, diagnostics, and therapy in snakes.
AB  - The pathogenesis of respiratory tract disease in snakes is complex. A snake must
      first be exposed to an infectious agent. If the snake is immunocompetent, then it
      usually prevails over the disease. When conditions of captive husbandry fall far
      less than those encountered in nature, snakes begin a battle that they have a
      hard time winning. Preventive education, preventive medicine, and quarantine
      allow clients to know that a health partnership is essential to accomplishing
      every veterinarian's mission, namely, a healthy pet.

PMID- 11228894
TI  - Respiratory biology and diseases of captive lizards (Sauria).
AB  - This article reviews respiratory diseases of lizards in clinics practice. A
      review of anatomy and physiology of the saurian respiratory tract sets the
      foundation for knowledge of normal function. The causes of noninfectious and
      infectious diseases are discussed. Diagnostic and treatment techniques to combat
      clinical disease are covered.

PMID- 11228895
TI  - Diseases of the respiratory tract of chelonians.
AB  - Diseases of the respiratory tract commonly occur in captive chelonians, and
      several diseases also have occurred in wild chelonians. Infectious causes include
      viruses, bacteria, fungi, and parasites. Herpesviruses have surfaced as important
      pathogens of the oral cavity and respiratory tract in Hermann's tortoise (Testudo
      hermanii), spur-thighed tortoise (Testudo graeca), and other tortoises in Europe
      and the United States. Herpesvirus-associated respiratory diseases also have been
      reported in the green turtle, Chelonia mydas, in mariculture in the Cayman
      Islands. Of diseases caused by bacteria, an upper respiratory tract disease
      caused by Mycoplasma sp has been reported in free-hanging and captive gopher
      tortoises in the southeastern United States and in desert tortoises in the Mojave
      Desert of the southwestern United States. Mycotic pulmonary disease is commonly
      reported in captive chelonians, especially in those maintained at suboptimal
      temperatures. An intranuclear coccidia has been seen in several species of
      captive tortoises in the United States, and, in one case, a severe proliferative
      pneumonia was associated with organisms in the lung. The most common
      noninfectious cause of respiratory disease in chelonians results from trauma to
      the carapace. Although pulmonary fibromas commonly occur in green turtles with
      fibropapillomatosis, for the most part, tumors of the respiratory tract are
      uncommon in chelonians.

PMID- 11228896
TI  - Amphibian respiratory diseases.
AB  - This article describes the diseases that commonly affect the lungs, gills, and
      nasal passages of frogs, toads, and salamanders. Although these organs often are
      affected by systemic infections, only diseases that are limited to the
      respiratory system are discussed. Gills of aquatic amphibians commonly are
      affected by poor water quality, infestations by protozoa or trematodes, or
      infections by water molds. Nematodes in the genus Rhabias are significant
      pulmonary pathogens in frogs and toads. The nasal passages of frogs, toads, and
      salamanders may be parasitized by Bufolucilia fly larvae.

PMID- 11228897
TI  - Grade inflation in internal medicine clerkships: results of a national survey.
AB  - BACKGROUND: There has been a discussion among medical educators concerning grade
      inflation; however, little has been written about it in the medical education
      literature. PURPOSE: A survey was developed to determine if grade inflation
      exists by gathering data about grading practices and by gathering the opinions of
      course directors from Internal Medicine clerkships. METHODS: The survey was
      administered during the 1996-1997 academic year to all 125 LCME accredited
      medical school Internal Medicine Clerkship Directors. Grading practices for 3
      separate academic years were obtained plus responses to questions about causes of
      and solutions for grade inflation. RESULTS: Eighty-three surveys were returned
      for a 66% response rate. There was a trend towards higher grades across the 3
      study years, with the 1995-1996 year being statistically significant. Forty-eight
      percent of the clerkship directors felt that grade inflation existed in their
      courses, and 43% felt that some students passed who should have failed.
      CONCLUSION: Statistically significant grade inflation exists in Internal Medicine
      clerkships. Most disturbingly, 43% feel we are unable appropriately to identify
      incompetent students.

PMID- 11228898
TI  - The collaborative health care team: the role of individual and group expertise.
AB  - BACKGROUND: Increasing costs of health care and rapid knowledge growth have led
      to collaboration among health care professionals to share knowledge and skills.
      PURPOSES: To characterize the qualitative nature of team interaction and its
      relation to training health professionals, drawing on theoretical and analytical
      frameworks from the sociocognitive sciences. METHODS: Activities in a primary
      care unit were monitored using observational field notes, hospital documents, and
      audio recordings of interviews and clinical interactions. RESULTS: The
      demarcation of responsibilities and roles of personnel within the team became
      fuzzy in practice. Continuous care was provided by primary care providers and
      specialized care by intermittent consultants. The nature of individual expertise
      required was a function of the patient problem and the interaction goal. These
      team characteristics contributed to the reduction of unnecessary and redundant
      interactions. CONCLUSIONS: Distributed responsibilities allow the team to process
      massive amounts of patient information, reducing the cognitive load on
      individuals. The uniqueness of individual professional expertise as it
      contributes to the accomplishment of team goals is highlighted, suggesting
      emphasis on conceptual competence in the development of individual professional
      education programs.

PMID- 11228899
TI  - Integrating a domestic violence education program into a medical school
      curriculum: challenges and strategies.
AB  - BACKGROUND: Domestic violence affects millions of women in the United States each
      year. Physicians are in a unique position to screen for violence in their
      patients' homes and refer individuals before they are injured or killed. All U.S.
      medical schools are expected to incorporate partner violence into their
      curricula. DESCRIPTION: The MCP Hahnemann School of Medicine has developed and
      integrated a domestic violence educational intervention program into the existing
      problem-based medical school curriculum. This educational intervention includes
      modification of an existing teaching case to include signs and symptoms specific
      to domestic violence, written learning objectives on domestic violence in the
      health care setting, relevant resource material, and a 3-hr training program
      conducted by an interdisciplinary teaching team. EVALUATION: Based on
      quantitative and qualitative data over a 3-year period, this domestic violence
      education program has been successfully integrated into an existing problem-based
      curriculum. Overall, the high student exam scores indicate the effectiveness of
      the teaching program. In addition, the students' evaluation of the program
      reflects a high level of student satisfaction with the curriculum presented on
      domestic violence. CONCLUSION: This article describes both the content of a
      domestic violence teaching program and the process used to integrate such a
      program into a medical school curriculum. Although medical schools and their
      teaching programs are uniquely structured, with slight modifications they are
      able to accommodate domestic violence teaching programs.

PMID- 11228900
TI  - Two techniques for teaching the estimation of prior probabilities.
AB  - BACKGROUND: Studies indicate that practicing clinicians do not employ
      quantitative techniques in diagnosis. If evidence-based approaches to clinical
      care are to succeed, there is a need to develop pedagogical tools to introduce
      the relevant techniques in clinical medicine. DESCRIPTION: This article describes
      2 heuristic techniques that can be used by clinical teachers to introduce
      residents and medical students to the practice of estimating prior probabilities
      in diagnostic reasoning. The techniques are the probability pie and the
      probability dollar. The techniques require learners to divide either a pie or a
      dollar according to the probability they assign in the differential diagnosis.
      The techniques also introduce related ideas such as likelihood ratios, posterior
      probabilities, diagnostic accuracy and intra- and interrater variability.
      EVALUATION: An example of a 60-year-old man presenting with chest pain is
      presented to illustrate the technique. CONCLUSION: This article presents a simple
      and clinically relevant method of introducing important concepts in quantitative
      reasoning. More systematic evaluation is required to assess its effectiveness.

PMID- 11228901
TI  - Using a standardized family to teach clinical skills to medical students.
AB  - BACKGROUND: The use of standardized patients has been an accepted instructional
      methodology in medical education for many years. A logical evolution of this
      methodology is the creation of a standardized patient family. DESCRIPTION: This
      article describes one such standardized family, the Jones family, and how the
      family is used to teach interpersonal skills, interviewing, communication,
      counseling, and history-taking skills to medical students. EVALUATION: After
      several years of using the Jones family, we have found that more comprehensive
      scripts need to be developed, that recruitment and retention of standardized
      patients for a year long program does not seem to be a problem, and that the
      value added by a standardized family greatly enhances the educational experience
      for students. A standardized family seems a logical educational vehicle for
      teaching continuity of care, confidentiality, contextual placement of medical
      information within family dynamics, cultural beliefs, community orientation, and
      generalism. CONCLUSION: A standardized family is a viable instructional
      methodology that deserves greater use in medical education.

PMID- 11228902
TI  - Unique issues of older medical students.
AB  - PURPOSE: Many persons applying to medical school have had other careers or
      experiences prior to their application. Comprising an increasing proportion of
      our student population, these older medical students often have unique
      difficulties differing from those of their younger peers. We undertook a 2-part
      study to evaluate possible differences in attitudes and beliefs between younger
      and older medical students. SUMMARY: We conducted the study in 2 parts. In the
      1st part, a focus group of students who would be 30 years old or older at the
      completion of medical school ("older students") was assembled to ascertain
      potential themes. Themes articulated by this group were then constructed into a
      questionnaire that was administered to the entire 4th-year class. Results of the
      questionnaire were evaluated qualitatively by content and quantitatively when
      appropriate. Eight students participated in the focus group. The themes expressed
      by the group included increased home responsibilities relative to their peers,
      lack of perceived respect by attendings and residents, and different learning
      strategies. Eighty-eight students completed the questionnaire. More older than
      younger students agreed with the statements that their previous experiences made
      them better learners (p = .06) and that their personal responsibilities made it
      difficult to study (p = .0001). On open-ended questions, the responses from the
      older students were longer and contained stronger language. CONCLUSION: Older
      medical students express unique concerns regarding the learning environment and
      the impact of medical school on their personal lives. This study provides
      preliminary information that our older students may have more special needs and
      concerns than traditional students.

PMID- 11228903
TI  - Asian/Pacific Islander women in medical education: personal and professional
      challenges.
AB  - PURPOSE: The purpose of this qualitative study was to identify the complex issues
      facing Asian/Pacific Islander (API) women students at one Midwestern medical
      school as they subjectively experience their medical training. Of particular
      interest was how students navigated family influences, career planning, and
      ethnic and gender stereotypes. SUMMARY: Sixty-five percent of the students
      reported that their parents exerted various degrees of encouragement or pressure
      to enter medicine. The remaining students said that the decision was entirely
      theirs (20%) or that the decision had been made for them (15%). Many reported the
      larger Asian "community" as a source of influence. A slight majority of students
      thought they were perceived by faculty as being "quiet," often too quiet. With
      only 1 exception, all of the students believed that their cultural identity
      influenced their specialty choice. Stressors reported by students centered on
      competition, achievement, and formation of intimate relationships (i.e., dating).
      CONCLUSIONS: Medical educators who provide personal and professional support for
      API women students should be keenly aware of the career, gender, and family
      issues that emerge at the intersection of API and Euro-American cultures. Faculty
      development should include an educational component on issues of concern to API
      students, men and women. Faculty also need to wrestle with the cultural values of
      "modesty, respect for authority, public self-consciousness, and other directness"
      as they intersect with assertion as a primary value found in Euro-American
      culture in general and in medical education in particular.

PMID- 11228904
TI  - Visual capture of touch: out-of-the-body experiences with rubber gloves.
AB  - When the apparent visual location of a body part conflicts with its veridical
      location, vision can dominate proprioception and kinesthesia. In this article, we
      show that vision can capture tactile localization. Participants discriminated the
      location of vibrotactile stimuli (upper, at the index finger, vs. lower, at the
      thumb), while ignoring distractor lights that could independently be upper or
      lower. Such tactile discriminations were slowed when the distractor light was
      incongruent with the tactile target (e.g., an upper light during lower touch)
      rather than congruent, especially when the lights appeared near the stimulated
      hand. The hands were occluded under a table, with all distractor lights above the
      table. The effect of the distractor lights increased when rubber hands were
      placed on the table, "holding" the distractor lights, but only when the rubber
      hands were spatially aligned with the participant's own hands. In this aligned
      situation, participants were more likely to report the illusion of feeling touch
      at the rubber hands. Such visual capture of touch appears cognitively
      impenetrable.

PMID- 11228905
TI  - On the transition from childhood amnesia to the recall of personal memories.
AB  - When adults are asked to report and date personal memories of their pasts, they
      show childhood amnesia, that is, diminished recall of experiences over the
      childhood years. This way of demonstrating the phenomenon was supplemented in the
      present study with a more direct approach: Participants reported events of early
      childhood that they knew they had experienced (because of family stories,
      photographs, etc.) but did not actually remember. The resulting cumulative
      relative frequency distributions produced by the two methods were substantially
      different, with the median age of remembered events being 6.07 years and of known
      events, 3.20 years. We suggest that the mean of these two ages, 4.64 years, gives
      a good indication of when childhood amnesia is eclipsed by personal memories in
      adults' recall of their personal pasts.

PMID- 11228906
TI  - A threatening intellectual environment: why females are susceptible to
      experiencing problem-solving deficits in the presence of males.
AB  - Does placing females in environments in which they have contact with males cause
      deficits in their problem-solving performance? Is a situational cue, such as
      gender composition, sufficient for creating a threatening intellectual
      environment for females--an environment that elicits performance-impinging
      stereotypes? Two studies explored these questions. Participants completed a
      difficult math or verbal test in 3-person groups, each of which included 2
      additional people of the same sex as the participant (same-sex condition) or of
      the opposite sex (minority condition). Female participants in the minority
      condition experienced performance deficits in the math test only, whereas males
      performed equally well on the math test in the two conditions. Further
      investigation showed that females' deficits were proportional to the number of
      males in their group. Even females who were placed in a mixed-sex majority
      condition (2 females and 1 male) experienced moderate but significant deficits.
      Findings are discussed in relation to theories of distinctiveness, stereotype
      threat, and tokenism.

PMID- 11228907
TI  - The Moses, mega-Moses, and Armstrong illusions: integrating language
      comprehension and semantic memory.
AB  - This study develops a new theory of the Moses illusion, observed in responses to
      general knowledge questions such as, "How many animals of each kind did Moses
      take on the Ark?" People often respond "two" rather than "zero" despite knowing
      that Noah, not Moses, launched the Ark. Our theory predicted two additional types
      of conceptual error demonstrated here: the Armstrong and mega-Moses illusions.
      The Armstrong illusion involved questions resembling, "What was the famous line
      uttered by Louis Armstrong when he first set foot on the moon?" People usually
      comprehend such questions as valid, despite knowing that Louis Armstrong was a
      jazz musician who never visited the moon. This Armstrong illusion was not due to
      misperceiving the critical words (Louis Armstrong), and occurred as frequently as
      the Moses illusion (with critical words embedded in identical sentential
      contexts), but less frequently than the mega-Moses illusion caused when Moses and
      Armstrong factors were combined.

PMID- 11228908
TI  - Caricature effects, distinctiveness, and identification: testing the face-space
      framework.
AB  - According to the multidimensional space framework, faces are represented as
      locations in a psychological face-space. Our aim was to test whether the
      locations of veridical, caricatured, and anticaricatured face stimuli in face
      space, derived from multidimensional scaling analyses, could account for
      identification accuracy and distinctiveness ratings for these stimuli.
      Caricatures were identified more accurately and rated as more distinctive than
      veridical images, whereas anticaricatures were identified less accurately but
      were not significantly less distinctive than veridical images. In the face-space
      derived from multidimensional scaling, caricatures were further from the origin
      and less densely clustered than veridical images, whereas anticaricatures were
      closer to the origin and located in denser regions of the space. A quantitative
      model successfully predicted identification performance from the spatial
      locations of the stimuli. In general, the physically transformed faces were
      systematically mapped in the psychological space.

PMID- 11228909
TI  - Competition-induced visual field differences in search.
AB  - Do visual field effects point to differences in cortical representation, or do
      they reflect differences in the way these representations are used by other brain
      regions? This study explored three attributes of visual search that provide
      strong evidence in favor of differences in use. Competition refers to the finding
      that visual field differences in search efficiency are larger in whole- than in
      half-field displays (both left-right and upper-lower half-fields). Task
      specialization refers to the finding that some tasks favor one hemisphere whereas
      other tasks favor the other hemisphere, even though the same stimulus displays
      are used in both tasks. Anatomical alignment refers to the finding that
      competition effects are altered if the quadrants of the visual display are not
      aligned with the cortical quadrants of the observer. We propose that visual field
      specialization in search is the result of a competition involving limited access
      to cortical visual representations by the extended neural networks of attention.

PMID- 11228910
TI  - The momentary realist.
AB  - Research suggests that people initially take their subjective experience of an
      object as an accurate reflection of the object's properties, and only
      subsequently, occasionally, and effortfully consider the possibility that their
      experience was influenced by extraneous factors. The two studies reported here
      demonstrate that this is true even when the extraneous factors are the person's
      own dispositions. Dispositionally happy and unhappy participants were falsely
      told that they had been subliminally primed with words that might have influenced
      their moods, and were then asked to identify those words. Dispositionally happy
      participants were more likely than dispositionally unhappy participants to
      conclude that they had been primed with positive words, but only when they made
      these judgments under time pressure. The results are discussed in terms of
      correction models of human judgment.

PMID- 11228911
TI  - When positive stereotypes threaten intellectual performance: the psychological
      hazards of "model minority" status.
AB  - Asian-American women's performance on a test of quantitative skill was studied as
      a function of whether their Asian, female, or individual identity was salient at
      the time of testing. In previous research, ethnicity salience was found to result
      in enhanced math performance among Asian women. However, the investigators relied
      on a subtle manipulation of ethnicity salience that likely did not invoke
      concerns about group reputation nor make salient the common cultural stereotypes
      concerning Asians' mathematical prowess. We induced a focus on ethnic identity in
      a manner that was likely to make other people's high performance expectations
      more salient. Under these conditions, ethnicity salience resulted in diminished
      ability to concentrate, which in turn led to significantly impaired math
      performance. Thus, although people commonly hold positive stereotypes about
      Asians' mathematical skills, making these stereotypes salient prior to
      performance can create the potential for "choking" under the pressure of high
      expectations.

PMID- 11228912
TI  - Shepard's universal law supported by honeybees in spatial generalization.
AB  - An animal that is rewarded for a response in one situation (the S+) is likely to
      respond to similar but recognizably different stimuli, the ubiquitous phenomenon
      of stimulus generalization. On the basis of functional analyses of the
      probabilistic structure of the world, Shepard formulated a universal law of
      generalization, claiming that generalization gradients, as a function of the
      appropriately scaled distance of a stimulus from S+, should be exponential in
      shape. This law was tested in spatial generalization in honeybees. Based on
      theoretically derived scales, generalization along both the dimensions of the
      distance from a landmark and the direction to a landmark followed Shepard's law.
      Support in an invertebrate animal increases the scope of the law, and suggests
      that the ecological structure of the world may have driven the evolution of
      cognitive structures in diverse animals.

PMID- 11228913
TI  - Testing between-family associations in within-family comparisons.
AB  - Using behaviorally discordant siblings to test for gene-behavior associations is
      a common tool in molecular genetics, because the within-family contrast offers a
      research design that avoids confounds inevitable in all between-family
      comparisons of unrelated individuals. We propose a similar strategy to assess the
      behavior-behavior associations on which much of psychological science is built.
      Between-family correlations of personality test scores (e.g., sensation seeking)
      and behavioral outcomes (e.g., substance use) may be mediated by variables that
      differ between families (e.g., social class or religiosity) and correlate with
      both personality and outcome. Contrasting twin and nontwin siblings who were
      highly discordant for behavioral correlates of substance use, we tested whether
      between-family behavioral correlations replicated within families. Some, but not
      all, did. Within-family analyses of behaviorally discordant siblings may find
      wide application in efforts to clarify the meaning of correlational research
      data.

PMID- 11228914
TI  - Left-hemisphere activation and deficient response modulation in psychopaths.
AB  - Psychopathic offenders have difficulty processing contextual or secondary cues
      once they have initiated goal-directed behavior or allocated attention to a
      primary task. To test the hypothesis that this deficit in response modulation is
      specific to conditions in which psychopaths' left-hemisphere resources are
      engaged, we administered a serial recall task to 21 incarcerated psychopaths and
      21 control subjects. Subjects were instructed to memorize eight words that were
      presented one at a time, each in one of the four corners of the visual display.
      Subjects' primary task was to recall the words in serial order. Then, without
      forewarning, they were asked to recall the words' locations. As predicted,
      psychopaths performed as well as control subjects in recalling words from the
      left and right spatial fields, but recalled significantly fewer locations from
      the right spatial field. Thus, psychopaths' deficient response modulation was
      specific to conditions in which their left-hemisphere resources were actively
      engaged.

PMID- 11228915
TI  - Separate and combined effects of location cuing and repetition priming on
      perceptual encoding of words.
AB  - We describe a methodology for investigating whether two manipulations exert
      independent effects on perception. This method avoids the strong scaling
      assumptions inherent to traditional analysis of variance techniques, and we used
      it to investigate the combined effects of cued visual attention and stimulus
      repetition. Subjects identified previously studied (primed) and new (unprimed)
      masked words that were presented to validly and invalidly cued locations for
      varying durations. Performance improved more rapidly with increasing exposure
      duration for primed than for unprimed, and for attended than for unattended,
      stimuli. We interpret this finding as indicating that both variables speed the
      rate of information acquisition. The speedup provided by priming and attention
      combined equaled the product of benefits for each alone, providing evidence they
      are serial, independent effects.

PMID- 11228916
TI  - Birds of a feather flock conjointly (?): rhyme as reason in aphorisms.
AB  - We explored the role that poetic form can play in people's perceptions of the
      accuracy of aphorisms as descriptions of human behavior. Participants judged the
      ostensible accuracy of unfamiliar aphorisms presented in their textually
      surviving form or a semantically equivalent modified form. Extant rhyming
      aphorisms in their original form (e.g., "What sobriety conceals, alcohol
      reveals") were judged to be more accurate than modified versions that did not
      preserve rhyme ("What sobriety conceals, alcohol unmasks"). However, the
      perceived truth advantage of rhyming aphorisms over their modified forms was
      attenuated when people were cautioned to distinguish aphorisms' poetic qualities
      from their semantic content. Our results suggest that rhyme, like repetition,
      affords statements an enhancement in processing fluency that can be misattributed
      to heightened conviction about their truthfulness.

PMID- 11228917
TI  - Features are also important: contributions of featural and configural processing
      to face recognition.
AB  - It has been suggested that face recognition is primarily based on configural
      information, with featural information playing little or no role. We investigated
      this idea by comparing the prototype effect for face prototypes that emphasized
      either featural or configural processing. In Experiment 1, participants showed a
      tendency to commit false alarms in response to nonstudied prototypes, and this
      tendency was equivalent for featural and configural prototypes. Experiment 2
      replicated this finding, and provided support for the assumption that the two
      types of prototypes differed in terms of featural and configural processing: Face
      inversion eliminated the prototype effect for configural prototypes but not for
      featural prototypes. These results suggest that both featural and configural
      processing make important contributions to face recognition, and that their
      effects are dissociable.

PMID- 11228918
TI  - The centercept: an estimable and meaningful regression parameter.
AB  - Linear regression is a mathematical model that is employed broadly throughout all
      of social science research. The choice of parameterization for linear models has
      important substantive and statistical implications. This article examines the
      typical parameterization chosen, which includes a parameter for slope and a
      parameter for the y-intercept. The article demonstrates that the centercept has
      an interpretive advantage over the traditionally used y-intercept and that the
      centercept is typically estimated more accurately.

PMID- 11228919
TI  - Preparation and equipment useful for surgery in small exotic pets.
AB  - Because many exotic pets are so small, the instrumentation and equipment used for
      surgery are different from in larger animals. Magnification greatly improves the
      surgeon's ability to accomplish surgeries in small patients and helps to provide
      hemostasis because small amounts of blood are significant in these tiny patients.
      Microsurgical instrumentation is important to allow for proper tissue handling
      and suture placement. Various other considerations, instrumentation, and
      equipment are useful when performing surgery on small exotic pets.

PMID- 11228920
TI  - Perioperative supportive care and monitoring.
AB  - Supportive care minimizes the adverse physiologic effects of anesthesia, surgery,
      and preexisting disease. Monitoring detects physiologic perturbations, ensures
      appropriate anesthetic depth, and assesses the efficacy of supportive care. The
      principles of monitoring and supportive care are similar in small exotic species;
      however, an understanding of comparative anatomy, physiology, and pathophysiology
      is necessary to apply these principles.

PMID- 11228921
TI  - Surgical sterilization in small mammals. Spay and castration.
AB  - The intrinsic physiologic and anatomic differences between small exotic mammals
      and the species that are more familiar to veterinary practitioners (i.e., dogs
      and cats) are substantial. This discussion is limited to rabbits, mice and rats
      (murid rodents), hamsters and gerbils (cricetid rodents), and guinea pigs and
      chinchillas (hystricomorph rodents). In addition to their anatomic and
      physiologic differences, differences in behaviors, such as their reaction to
      stress and pain, exist. Preoperative and postoperative care, basic surgical
      techniques unique to these species, and useful materials are discussed.

PMID- 11228922
TI  - Nonreproductive surgery in small mammals.
AB  - The sophistication of soft-tissue surgery techniques in small mammals is
      increasing rapidly. Exotic animal practitioners must be familiar with the
      diseases, conditions, and anatomic variations of each small-mammal species. The
      small size of these patients should not preclude the use of technologic advances
      available for other small animals. Despite these challenges, successful
      resolution of surgical problems in small exotic mammals is not only possible but
      also should be the expected result of veterinarians' efforts in such cases.

PMID- 11228923
TI  - Abdominal surgery in ferrets.
AB  - Surgical procedures in ferrets share similarities with those performed in other
      species, but attention must be paid to important anatomic and physiologic
      differences. As the numbers of these endearing animals kept as pets is steadily
      increasing, veterinary practices are presented with more requests for a greater
      variety of surgical procedures.

PMID- 11228924
TI  - Miscellaneous surgeries in ferrets.
AB  - This article describes the most common extra-abdominal surgeries performed in
      ferrets, including anal sacculectomy for descenting, mammary and prepucial
      adenoma or adenocarcinoma removal, chordomas, and perineal urethrostomy.
      Thoracotomy and special considerations for performing surgery on ferrets also are
      discussed.

PMID- 11228925
TI  - Surgery of the avian reproductive and gastrointestinal systems.
AB  - Surgery of the female reproductive system is the most commonly indicated intra
      abdominal surgery of avian patients. Surgery of the male reproductive system and
      avian gastrointestinal tract are less commonly indicated but are occasionally
      necessary. Indications for surgery of the female reproductive tract include egg
      laying-related disorders, dystocia, egg binding, damage or trauma to the oviduct,
      oviductal torsion and volvulus, abnormal egg production, biopsy or culture of the
      oviduct, internal laying, egg related coelomitis, oviductal impaction, oviductal
      or ovarian neoplasia, ovarian cysts, or as a sterilization procedure to stop egg
      laying. Indications for surgery of the male reproductive tract include castration
      (most often as a treatment of behavioral problems) and treatment of testicular
      neoplasia. Indications for gastrointestinal tract surgery include repair of
      traumatic injury, foreign-body retrieval, obstructive disease, as a treatment for
      neoplasia, and as a diagnostic tool to retrieve tissue for biopsy. Avian
      reproductive anatomy and physiology are reviewed. Presurgical and postsurgical
      patient care ensures successful recovery. Lateral, horizontal, and midline
      approaches may be preferred based on indication or concurrent disease. Approaches
      are described in detail. Indications and descriptions of surgery conclude this
      article.

PMID- 11228926
TI  - Surgery of the avian respiratory system.
AB  - The avian respiratory system is different from that of mammals. Although some
      surgical techniques can be adapted from those used in mammals, many are unique to
      avian patients (e.g., choanal atresia correction and air sac cannulation). This
      article reviews the common surgeries of the upper and lower respiratory systems
      and describes surgical techniques for the treatment of chronic sinusitis and
      cranial coelomic mass removal.

PMID- 11228927
TI  - Nonreproductive surgery in reptiles.
AB  - As reptiles have gained popularity as pets, veterinarians are more frequently
      called on to perform surgical procedures on these pets. Veterinarians must have a
      basic understanding of the anatomic and physiologic differences between reptilian
      and mammalian companion animals. This article reviews some basic points about
      reptilian anatomy and physiology that are important to consider when performing
      surgery on reptilian patients. This article covers approaches to the coelomic
      cavity in the different groups of reptiles and some basic concepts regarding
      surgery on different, nonreproductive systems in these reptiles.

PMID- 11228928
TI  - Reproductive surgery in reptiles.
AB  - Reptiles are commonly presented to veterinarians for reproductive problems.
      Often, these problems require surgical intervention. This article discusses some
      of the major causes of dystocia in reptiles and describes the surgical treatment
      of the female reproductive tract, including ovariectomy,
      ovariosalpingohysterectomy, and prolapse of the shell gland. Descriptions of
      surgical intervention in male reptiles include orchidectomy and paraphimosis.

PMID- 11228929
TI  - Surgery of amphibians.
AB  - This article is an introduction to common amphibian surgical techniques. No
      overwhelming obstacles preclude incorporating amphibian surgeries into the
      repertoire of veterinary clinicians. With the proper tools and reference
      materials and a little practice, the skills needed may be readily acquired.

PMID- 11228930
TI  - Surgery in fish.
AB  - Surgery in fish is feasible and practical for clinical and research applications.
      Certain adjustments in standard surgical procedures are necessary to accommodate
      piscine tissue handling, skin sensitivity, aqueous respiration, anatomic
      variations, and patient size. General considerations for fish surgery, including
      anesthesia, presurgical evaluation, equipment, suture selection, and surgical
      site preparation, have been presented here. Procedures described include
      celiotomy, enucleation, pseudobranchectomy, swim bladder surgery, gonadectomy,
      liver and kidney biopsy techniques, telemetry device implantation, and vascular
      catheterization.

PMID- 11228931
TI  - Differences in reproductive endocrinology between Asian men and Caucasian men--a
      literature review.
AB  - This review provides an overview of the literature on aspects of reproductive
      endocrinology wherein Asian men may differ from Caucasian, notably, prostatic
      neoplasm and the sensivity to pharmacological regimens of male contraception.
      Both genetic and environmental factors, such as nutrition, might be relevant.
      Asian men residing in Asia seem to be relatively protected from clinical
      prostatic neoplasm while the prevalence of preclinical prostatic neoplasm is not
      different. Migration to an area with a higher prevalence reduces this difference
      but does not undo it. With regard to prostatic neoplasm the following factors
      have been considered as relevant in Asian men: 1) a reduction in 5 alpha
      reductase level, 2) decreased levels of androgenic ketosteroid precursors of 5
      alpha-reduced androgen metabolites, 3) the decreased presence of a P53 mutation,
      4) a higher CAG-repeat length of the androgen receptor, 5) a possible higher
      level of physical activity, 6) differences in sexual activity. Furthermore, Asian
      men respond to a higher degree with azoospermia in response to contraceptive
      steroids. Possible explanations offered for the more pronounced response to
      contraceptive steroids are: 1) differences in testicular structure and decreased
      spermatogenic potential, 2) an earlier and more marked suppression in LH
      secretion by exogenous androgens. The differences may be due to genetical and/or
      environmental factors influencing the peripheral testosterone metabolism. Dietary
      factors such as the higher intake of phytoestrogens in Asians might exert effects
      on 5 alpha-reductase activity and/or on sex hormone binding globulin (SHBG)
      levels, thus having an impact on the biological efficacy of circulating
      androgens.

PMID- 11228932
TI  - No-scalpel vasectomy outside China.
AB  - Since 1985, the no-scalpel vasectomy technique has been widely used outside
      China. The prevalence of this technique has helped to increase the acceptability
      of male sterilization in many parts of the world. More than 5000 physicians in
      twenty-five developing countries have been trained in the no-scalpel vasectomy
      technique. In the United States in 1995, nearly one third of vasectomies employed
      the no-scalpel technique, and in the whole Northern American region, a total of
      1100 doctors have been made familiar with the technique. Doctors believe that
      there are several advantages of the no-scalpel technique, including no incision,
      no stitches, faster procedure, faster recovery, less chance of bleeding, less
      discomfort and high efficacy. The key steps of the technique include fixation of
      the vas and infiltration anaesthesia of the spermatic cord, as well as grasping,
      delivering and isolating the vas. No-scalpel technique provides a good approach
      to expose the vas, in conjunction with which, different vas-end occlusion methods
      may be used.

PMID- 11228933
TI  - Medical treatment of idiopathic oligozoospermia and male factor subfertility.
AB  - Pharmaceutical treatment for the so-called idiopathic oligozoospermia (I. O.) is
      possible and effective in a fair proportion of patients with the syndrome
      provided that appropriate investigative procedures may identify the major
      disorder or its level of disruption, this abnormality is reversible and
      appropriate prognostic indices for the treatment's success are devised and
      validated. According to the evidence available, minimal evaluation and prognostic
      indices for treatment eligibility in normogonadotropic men with I. O. include a
      routine work-up but, mainly, microscopical assessment of spermatogenesis and
      appraisal of Sertoli cell's functional capacity. Published data indicate that men
      with hypospermatogenesis without maturational arrest, respond favorably to agents
      stimulating Sertoli cells and germinal epithelium with increased sperm
      production. Furthermore, Sertoli cell activity as judged by cell-specific indices
      such as inhibin B secretion, may provide additional discriminating power to the
      microscopical picture of the testis. In this context, precise identification of
      the causative factor(s), together with the establishment of prognostic indices
      are the most important criteria on which the decision, for or against medical
      treatment in I. O., should be based. Obviously, further basic research and
      clinical trials are urgently needed in this particular field, and this should be
      a major task for clinical andrologists.

PMID- 11228934
TI  - Male contraception: prospects for the new millennium.
AB  - Effective regulation of human fertility has global consequences in terms of
      resource depletion, pollution and poverty. Current family planning services
      predominantly target a female clientele with few significant developments in male
      fertility regulation for over a century. The last two decades have witnessed a
      gathering interest, initially from the scientific community, and laterally from
      industry, in the development of safe, reliable, reversible methods of
      contraception for men. This review summarises the methods of male fertility
      regulation which are currently available and critically examines the published
      data on novel developments in male hormonal contraception which offer the
      potential of improved contraceptive choice for all in new millennium.

PMID- 11228935
TI  - Transgenic technologies for the study of epididymal function.
AB  - Sperm mature and acquire the capacity for fertilization during their transit
      through the epididymis, however little is known of the molecular events that
      comprise sperm maturation. Recent advances in transgenic mouse technology hold
      promise for illumination of this process. Most of the existing infertile,
      transgenic mouse lines seem to have defects in epithelial structure or sperm
      transport rather than direct defects in the maturation of sperm. Temporally and
      spatially restricted targeted disruptions of epididymal specific genes should
      provide great insight into the epididymal contribution to sperm maturation.

PMID- 11228936
TI  - Interference with the formation of the epididymal microenvironment--a new
      strategy for male contraception?
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) or the small
      conductance cAMP-activated chloride channel encoded by the CFTR gene has been
      shown to play an important role in the formation of the epididymal fluid
      microenvironment. Recent work in our laboratory has shown that this protein is
      also expressed by developing germ cells indicating a role of this protein in
      spermatogenesis. In view of the fact that the CFTR gene has a far reaching and
      widespread effect on human reproduction, understanding the role of CFTR in the
      male reproductive tissues and its intervention by pharmacological agents can open
      a new avenue of research into the development of novel male contraceptives.

PMID- 11228937
TI  - Hormonal contraception for human males: prospects.
AB  - Development of an ideal hormonal contraceptive for man has been the goal of
      several research workers during the past few decades. Suppression of pituitary
      gonadotropic hormones, which in turn would inhibit spermatogenesis while
      maintaining normal libido and potential has been the approach for a contraceptive
      agent. Intramuscularly administered and orally active testosterone or
      testosterone in combination with progesterone have been shown to cause inhibition
      of spermatogenesis resulting in azoospermia in normal men. Similarly testosterone
      has been used in combination with gonadotropin releasing hormone antagonists and
      agonists to inhibit pituitary gonadotropic hormone release. Immunological
      approach to neutralize the circulating levels of follicle stimulating hormone has
      also been shown to cause inhibition of spermatogenesis. The available literature
      shows that testosterone causes reversible azoospermia without any significant
      side effects in Asian population effectively and appears to be a promising
      chemical for control of fertility in man.

PMID- 11228938
TI  - Physiological significance of nitrergic transmission in human penile erection.
AB  - The corpora cavernosa (CC) muscles of the human penis and their structural
      arrangements are essential for the physiology of erection. Contraction of this
      muscle causes detumescence, and relaxation, tumescence. The motor excitatory
      neurotransmission is adrenergic, acting through the alpha adrenoceptors.
      Continuous adrenergic transmitter (noradrenaline) release is necessary for the
      maintenance of non-erectile (contractile) state of the penis. The inhibitory
      neurotransmitter that relaxes CC muscle to produce erection is nitrergic i.e.,
      the chemical messenger being nitric oxide (NO). The latter can also be released
      from cavernous endothelium. Presence of NO increases intracellular cGMP through
      activation of the enzyme guanylate cyclase. This causes relaxation of CC muscle.
      Phosphodiesterase type 5 (PDE5) is responsible for the degradation of cGMP and
      regulation of CC muscle tone. Specific PDE inhibitors such as sildenafil enhance
      the intracellular cGMP to improve erection. Increase in intracellular cAMP can
      also bring about pharmacological erection in man (e.g. PGE1, papaverine and
      histamine). Inhibition of excessive adrenergic tone with appropriate alpha
      adrenergic blocking agents (e.g. phentolamine) can also contribute to the onset
      of pharmacological erection.

PMID- 11228939
TI  - Protein profiles in various epididymal segments of normal and castrated rats.
AB  - AIM: Epididymal proteins are known to play an important role in the maturation of
      spermatozoa. We ought to determine if there are regional differences in androgen
      dependent epididymal proteins. METHODS: A group of adult rats was castrated and
      epididymides were removed three days following castration. The epididymides were
      dissected into caput, corpus and cauda segments, homogenized, and proteins were
      fractionated by anion exchange HPLC. Proteins in selected fractions were resolved
      by SDS-PAGE and visualized by silver staining. RESULTS: It was observed that the
      levels of multiple proteins drastically reduced in the various regions of
      epididymis of the orchiectomized rats. CONCLUSION: The epididymal proteins appear
      to be useful markers to study androgenic action in the epididymis.

PMID- 11228940
TI  - Quantitative and qualitative changes in serum luteinizing hormone after
      injectable testosterone undecanoate treatment in hypogonadal men.
AB  - AIM: To clarify the immuno-active LH (i-LH) and bioactive LH (b-LH) responses and
      qualitative changes in the circulating LH to testosterone undecanoate (TU)
      injection. METHODS: Eight men with Klinefelter's syndrome were recruited for the
      study. They received crossover injections of TU at doses of 500 and 1000 mg.
      Serum i-LH and b-LH levels before and at various time intervals after TU
      injection were measured and the serum i-LH, b-LH, b-LH/i-LH (B/I) and
      testosterone/sex hormone-binding globulin (T/SHBG) ratio in LH-responders and LH
      non-responders were compared. RESULTS: A parallel suppression of serum i-LH and b
      LH was consistent with their overall high correlation between each other (r =
      0.84, P < 0.001). Mean serum i-FSH levels were decreased by TU injection at both
      doses without dose-response effects. LH-responders had lower baseline serum i-LH
      and b-LH, and higher E2 levels and T/SHBG ratio. There was a quantitative change
      in serum LH as induced by TU without qualitative change within LH-responders os
      LH-non-responders. CONCLUSION: A high loading dose (1000 mg) of TU is important
      for the initial suppression of LH. With the lower dose (500 mg), repeated
      injections will be required to attain such LH suppression for the purpose of
      fertility regulation. The lower baseline serum i-LH level may be an intrinsic
      characteristic of LH-responders.

PMID- 11228941
TI  - Quantitative (stereological) study on the spermatozoal storage capacity of
      epididymis in rats and monkeys.
AB  - AIM: To investigate the spermatozoal production rate of the testis and the
      spermatozoal storage capacity of the epididymis in monkeys and rats. METHODS: The
      number of the late spermatids (steps 13-14 in the monkey or steps 15-19 in the
      rat) per testis and the number of spermatozoa per epididymis were estimated in 6
      normal adult monkeys (Macaca fascicularis) and 6 normal adult SD rats on 25
      microns-thick methacrylate-embedded sections using a contemporary unbiased and
      efficient stereological method--the optical disector. The diameter and length of
      the efferent ductules and ductus epididymidis and the volume of the epididymal
      fluid in the tubules were also estimated. RESULTS: The total number of the late
      spermatids per testis was 2902 +/- 749 (million, x +/- s) in the monkey, or 179
      +/- 31 in the rat; the number of spermatozoa per epididymis was 3235 +/- 1835 in
      the monkey, or 241 +/- 76 in the rat. CONCLUSION: A large number of spermatozoa
      was densely packed and stored in the ductus epididymidis; the epididymal transit
      time for spermatozoa was around 5 days in monkeys or 11 days in rats.

PMID- 11228942
TI  - Re "No-scalpel vasectomy outside China".

PMID- 11228943
TI  - Re "Three new methods for male contraception".

PMID- 11228944
TI  - Perceived vertical and lateropulsion: clinical syndromes, localization, and
      prognosis.
AB  - We present a clinical classification of central vestibular syndromes according to
      the three major planes of action of the vestibulo-ocular reflex: yaw, roll, and
      pitch. The plane-specific syndromes are determined by ocular motor, postural, and
      perceptual signs. Yaw plane signs are horizontal nystagmus, past pointing,
      rotational and lateral body falls, deviation of perceived straight-ahead to the
      left or right. Roll plane signs are torsional nystagmus, skew deviation, ocular
      torsion, tilts of head, body, and perceived vertical in a clockwise or
      counterclockwise direction. Pitch plane signs are upbeat/downbeat nystagmus,
      forward/backward tilts and falls, deviations of the perceived horizon. The thus
      defined vestibular syndromes allow a precise topographic analysis of brainstem
      lesions according to their level and side. Special emphasis is placed on the
      vestibular roll plane syndromes of ocular tilt reaction, lateropulsion in
      Wallenberg's syndrome, thalamic and cortical astasia and their association with
      roll plane tilt of perceived vertical. Recovery is based on a functionally
      significant central compensation of a vestibular tone imbalance, the mechanism of
      which is largely unknown. Physical therapy may facilitate this central
      compensation, but this has not yet been proven in prospective studies.

PMID- 11228946
TI  - Evaluation of a manual wheelchair interface to computer games.
AB  - The sedentary lifestyle of many people with spinal cord injury (SCI) has lead to
      cardiovascular diseases being a major health concern. A suitable exercise program
      may help improve the SCI individual's cardiovascular fitness level. GAMEWheels is
      an interface between a custom wheelchair roller system and a computer that
      enables an individual to control computer video games by driving his or her
      wheelchair. The purpose of Phase 1 was to evaluate the design of the GAMEWheels
      system and to determine the type of computer video game that is likely to
      motivate wheelchair users to exercise. Phase 2 included physiologic testing of
      wheelchair users and the GAMEWheels system to investigate whether the system
      elicits an exercise training response. Thirty-five subjects were recruited to
      evaluate the GAMEWheels by playing three commercial computer games (Phase 1) and
      to identify the computer game that they would prefer to use when exercising. The
      feedback from Phase 1 was used with test subjects to verify that the GAMEWheels
      system elicits an exercise training effect (Phase 2). Phase 2 included 10
      subjects using the GAMEWheels system to play Need for Speed II. During game play,
      physiologic data were collected and the subjects' oxygen consumption and heart
      rate were analyzed. Analysis showed that the GAMEWheels system induced nine
      subjects to reach their training zone, defined as 50% and 60% of their maximum
      oxygen consumption and heart rate, respectively. This study demonstrates that the
      GAMEWheels system elicits an exercise training response.

PMID- 11228945
TI  - Comparison of partial body weight-supported treadmill gait training versus
      aggressive bracing assisted walking post stroke.
AB  - PURPOSE: To test the hypothesis that partial body weight-supported treadmill
      training (PBWSTT) provides more effective gait training than an equally
      supportive but less physiologic aggressive bracing assisted walking (ABAW)
      program. METHODS: Following informed consent, patients participating in an
      inpatient rehabilitation program with significant leg weakness and need for at
      least moderate assistance for walking, without orthostatic hypotension,
      symptomatic dyspnea, or angina pectoris were randomized to receive PBWSTT vs.
      ABAW. PBWSTT was provided by a commercially available, overhead motorized hoist
      attached to a parachute-type body harness, which provided partial support of the
      patient's weight over a treadmill. Therapists assisted with weight shifting, leg
      advancement, and foot placement as needed. ABAW included aggressive early
      therapist-assisted ambulation using knee-ankle combination bracing and hemi-bar
      if needed. Treatment sessions of up to 45 minutes per day, five days per week
      were given as tolerated for the duration of the inpatient stay or until patients
      could walk over-ground unassisted. All patients had an additional 45-minute
      session of functionally oriented physical therapy each day with or without
      bracing as judged appropriate by the patient's individual therapist. RESULTS:
      Fifty-six patients a mean age of 71 +/- 1 SEM were enrolled 40 +/- 3 days post
      stroke. Although the outcome of the two groups as a whole did not differ, a
      subgroup with major hemispheric stroke defined by the presence of hemiparesis,
      hemianopic visual deficit, and hemihypesthesia who received more than 12
      treatment sessions showed significantly better over-ground endurance (90 +/- 34
      vs. 44 +/- 10 meters) and speed scores (12 +/- 4 vs. 8 +/- 2 meters/minute) for
      PBWSTT vs. ABAW, respectively. CONCLUSIONS: PBWSTT and ABAW are equally effective
      gait training techniques except for a subset of patients with major hemispheric
      stroke who are difficult to mobilize using ABAW alone.

PMID- 11228947
TI  - Upper extremity control in adults post stroke with mild residual impairment.
AB  - Motor control deficits in the upper extremity (UE) ipsilateral to the side of
      brain damage persist after stroke, but it is not known if the presence of these
      deficits is related to impairment of the contralateral UE. The purpose of this
      study was to investigate whether motor deficits are present in the ipsilateral UE
      when contralateral UE impairment is mild in adults with chronic stroke. Right
      handed adults (10 controls, 10 right stroke, 10 left stroke) performed rapid
      continuous aiming movements to small and large targets. Using kinematic analysis,
      temporal measures of the movement were defined, including movement time (MT) and
      the three components of MT: acceleration, deceleration, and dwell time (i.e.,
      time on target). Participants with right stroke had prolonged MT only with the
      left UE, primarily due to longer dwell times. Participants with left stroke had
      prolonged MT with both UEs as a result of longer dwell times. The results
      indicate that control deficits of the ipsilateral UE are evident in individuals
      with left but not right brain damage who have minimal impairment of the
      contralateral UE. These findings are consistent with the role of the left
      hemisphere in the control of both UEs.

PMID- 11228948
TI  - Influence of thoracoabdominal movement on pulmonary function in patients with
      Parkinson's disease: comparison with healthy subjects.
AB  - Patients with Parkinson's disease (PD) may develop pulmonary dysfunction, but the
      pathogenesis remains unclear. We investigated a correlation between
      thoracoabdominal movements and pulmonary function in seven patients with PD and
      14 healthy controls. We measured vital capacity (VC) and forced vital capacity
      (FVC) using an autospirometer, and measured chest and abdominal movements using a
      respiratory inductance plethysmography by fixing transducers on the rib cage and
      umbilicus. Patients with PD had significantly decreased % VC (90.3 +/- 17.1 vs
      105.8 +/- 13.9%), chest movement (271.3 +/- 79.6 vs. 375.2 +/- 126.7% VT) and
      abdominal movement (217.6 +/- 93.5 vs. 247.4 +/- 100.2% VT) with 100% VT being an
      average volume of chest and abdomen at rest during measurement of VC. Patients
      with PD also had significantly decreased % FVC (74.4 +/- 20.6 vs. 97.6 +/-
      14.1%), chest movement (246.2 +/- 115.2 vs. 344.5 +/- 126.4% VT) and abdominal
      movement (160.3 +/- 105.6 vs 207.6 +/- 104.7% VT) with 100% VT being an average
      volume of chest and abdomen at rest during forced maximal inspiration. Based on
      the results, we conclude that a reduction of % VC in patients with PD correlated
      with chest movements, while a reduction of % FVC correlated with abdominal
      movement in patients with PD.

PMID- 11228949
TI  - Expression of the netrin receptor UNC-5 in lamprey brain: modulation by spinal
      cord transection.
AB  - The sea lamprey recovers from spinal cord transection by a process that involves
      directionally specific regeneration of axons. The mechanisms underlying this
      specificity are not known, but they may involve molecular cues similar to those
      that guide the growth of spinal cord axons during development, such as netrins
      and semaphorins. To test the role of guidance cues in regeneration, we cloned
      netrin and its receptor UNC-5 from lamprey central nervous system (CNS) and
      studied their expression after spinal cord transection. In situ hybridization
      showed that (1) mRNA for netrin is expressed in the spinal cord, primarily in
      neurons of the lateral gray matter and in dorsal cells; (2) mRNA for UNC-5 is
      expressed in lamprey reticulospinal neurons; (3) following spinal cord
      transection, UNC-5 message was dramatically downregulated at two weeks, during
      the period of axon dieback; (4) UNC-5 message was upregulated at three weeks,
      when many axons are beginning to regenerate; and (5) axotomy-induced expression
      of UNC-5 occurred primarily in neurons whose axons regenerate poorly. Because the
      UNC-5 receptor is thought to mediate the chemorepellent effects of netrins,
      netrin signaling may play a role in limiting or channeling the regeneration of
      certain neurons. These data strengthen the rationale for studying the role of
      developmental guidance molecules in CNS regeneration.

PMID- 11228950
TI  - Reassessment of the incidence of complex regional pain syndrome type 1 following
      stroke.
AB  - Previous literature has suggested that reflex sympathetic dystrophy, also known
      as complex regional pain syndrome (CRPS) type 1, is a relatively common finding
      after a stroke. However, much of this data was obtained before patients routinely
      received early intensive inpatient rehabilitation. The purpose of this study is
      to reevaluate the incidence of CRPS type 1 following an acute first stroke.
      Subjects admitted to an acute rehabilitation setting for stroke with no other
      concomitant neurologic or orthopedic injuries between October 1, 1996, and May
      31, 1997, were studied. At admission and once a week until discharge, subjects
      were evaluated for shoulder pain, decreased passive range of motion of the
      shoulder, wrist/hand pain, edema, and skin changes. If three of these five
      criteria were positive, the subjects underwent a triple-phase bone scan (TPBS).
      Bone scan findings consistent with CRPS type 1 were taken as confirming the
      diagnosis. Of 64 subjects, 13 underwent bone scans, with only one positive
      result. Thus our study revealed a 1.56 percent incidence of CRPS type 1 following
      a first stroke. This incidence is much lower than the historically accepted 12.5
      percent. We speculate that this low figure is related to early comprehensive
      rehabilitation that included proper upper extremity positioning and early
      mobilization with sensory stimulation.

PMID- 11228951
TI  - Effects of aerobic treadmill training on gait velocity, cadence, and gait
      symmetry in chronic hemiparetic stroke: a preliminary report.
AB  - It is widely assumed that only limited improvement in functional mobility is
      possible beyond the subacute period following ischemic stroke. Contrary to this
      notion, we studied "neurologically plateaued" stroke patients with chronic
      hemiparesis to assess whether a "task-oriented" treadmill-training regimen would
      improve walking speed, cadence, and gait cycle symmetry on a modified "Get-Up and
      Go" task. Five male patients with a mean age of 60.4 +/- 2.7 years (mean +/-
      S.D.) status post ischemic stroke (> 6 months prior) participated in this
      nonrandomized low-intensity treadmill exercise pilot study three times/week for 3
      months. All patients had mild to moderate gait asymmetries due to residual
      hemiparesis. Patients were videotaped before and after 3 months of treadmill
      aerobic exercise (AEX) while performing a functional task consisting of arising
      from a chair, walking 3.1 m without an assistive device as fast as safely
      possible, and returning to sit. Gait events were timed using a 2-D Peak Motus
      video analysis system. After 3 months AEX training, times for the overall "get-up
      and return-to-sit" (GURS) task and the "straight-away walk" (SAW) segment
      decreased from 8.2 +/- 1.4 sec to 6.5 +/- 0.8 sec (mean +/- SEM) (p < 0.05), and
      from 3.7 +/- 1 sec to 2.8 +/- 0.7 sec (p < 0.05), respectively. These data
      represent improvements of 21% and 24% for the GURS and SAW segments,
      respectively. Mean velocity increased from 0.9 +/- 0.2 to 1.2 +/- 0.21 m/sec, a
      33% improvement (p < 0.01). Mean cadence (steps/min) increased from 89 +/- 9 to
      97 +/- 8, a 9% increase (p < 0.05). Mean stance and swing duration diminished for
      both paretic (P) and nonparetic (NP) limbs, and the intralimb stance/swing ratio
      values moved toward normal for both the paretic and nonparetic limbs. However,
      these latter changes reached significance only for the P limb. Interlimb stance
      symmetry was unchanged. The more impaired subjects experienced the greatest gains
      in gait velocity and temporal measures. Collectively, these findings indicate
      that treadmill exercise improves functional overground mobility in individuals
      with chronic, stable hemiparesis.

PMID- 11228952
TI  - Doing it with mirrors: a case study of a novel approach to neurorehabilitation.
AB  - Arm amputees can experience the perception of movement of a phantom limb while
      looking at a mirror reflection of the moving, intact arm superimposed on the
      perceived phantom. Such use of a mirror to provide illusory visual feedback of
      movement can be useful in rehabilitation of hemiparetic patients. In this case
      report, we describe the successful application of "mirror therapy" to the post
      stroke rehabilitation of a patient with poor functional use of an upper
      extremity, due mainly to somatosensory deficits. Mirror therapy facilitated
      employment of a motor copy strategy (bimanual movements) and later progression to
      "forced use" of the affected arm. The end result was increased functional use of
      the affected upper limb.

PMID- 11228953
TI  - Odour measurements for sewage treatment works.
AB  - Public concern over odours from sewage treatment works is increasing. More people
      are being exposed to odours, due to development around existing works or
      construction of new works. Increased awareness of both the environment and
      individual rights has meant people are now more likely to complain. Odour
      abatement and control is a major issue for sewage works operators. To control
      odours, they must first be measured. This is no easy task as response to odours
      is subjective. Our understanding of the sense of smell is incomplete, and there
      is no single measure that will directly relate to the likelihood of complaint.
      Odour measurement has often been regarded as an art as opposed to a science.
      Odour measurement techniques fall into two classes. Sensory measurements employ
      the human nose and measure the effects of the odour as perceived by an observer.
      Analytical measurements characterise odours in terms of their chemical
      composition and attempt to quantify the odorants present. Both methods are less
      than ideal--sensory measurements can be overly subjective and the interpretation
      of results requires care. Analytical measurements are complicated by the large
      number of odorants present, often at concentrations close to detection limits.
      Our incomplete understanding of odour perception makes linking analytical and
      sensory measurements difficult. This paper reviews the methods applied to sewage
      treatment works odour measurement. Sensory and analytical measurements are
      reviewed, along with a recent development, the electronic nose.

PMID- 11228954
TI  - Ammoniacal bromamines: a review of their influence on bromate formation during
      ozonation.
AB  - Ammonia can inhibit the formation of bromate in ozonated drinking water by
      reacting with free bromine (HOBr/OBr-), an intermediate in bromate formation, to
      form bromamines. Bromamines do not participate in bromate formation, however,
      they will decay due to autonomous decomposition and through reaction with ozone
      and hydroxyl radicals. The reaction with ozone controls the overall decay rate.
      This reaction also results in a net loss of ammonia from the system, leading to
      the possibility that all ammonia may be oxidized before the ozone residual in the
      water is eliminated, allowing bromate formation to resume. This paper presents a
      review of our understanding of bromamine chemistry and identifies areas that are
      not adequately understood, which may prevent an accurate estimation of ammonia's
      impact on bromate formation.

PMID- 11228955
TI  - Sorption kinetic analysis for the removal of cadmium ions from effluents using
      bone char.
AB  - The adsorption of cadmium ions onto bone char has been studied using a batch
      adsorber. The experimental data was analyzed using four sorption kinetic models-
      the pseudo-first order, the Ritchie second order, the modified second order and
      the Elovich equations--to determine the best-fit equation for the sorption of
      metal ions onto bone char. The best-fit equation was identified using the sum of
      the errors squared (SSE). Finally, equilibrium studies were used to evaluate the
      sorption capacity of bone char for cadmium ions and experimental results showed
      this to be 0.57 mmol g-1 at an equilibrium solution concentration of 3.0 mmol dm
      3. Since the sorption capacity is relatively high, bone char can be considered as
      a suitable sorbent for the adsorption of cadmium in wastewater treatment systems.

PMID- 11228957
TI  - Simulation of biological degradation of aromatic amines in river bed sediments.
AB  - Testfilter experiments are reported for river Elbe water spiked with aromatic
      amines in order to determine biodegradation rates. For river Elbe water the mean
      degradation rate of DOC (C0 = 6.64 mg l-1) was 26.7 +/- 8.8% after 6.8 days. No
      significant effect on the DOC degradation rate was observed with the addition of
      aromatic amines. Large differences in the biodegradation behaviour of the
      aromatic amines were observed: aniline was eliminated within 3 h, whereas the
      degradation of 2-nitroaniline was only 40% after 14 h effective contact time.
      Degradation curves were mostly of a simple logarithmic type, demonstrating first
      order kinetics. The degradation rate of 2,4,6-trichloraniline increased by a
      factor of 20 within 6 weeks due to the adaptation of the testfilter biofilm. A
      linear relationship between available pKa-values and the logarithm of the
      experimental degradation rates was found. Thus, the results of the testfilter
      experiments may be extended to the estimation of the biodegradability of non
      tested aromatic amines.

PMID- 11228956
TI  - Kinetic modeling of liquid-phase adsorption of reactive dyes and metal ions on
      chitosan.
AB  - The rates of adsorption of three commercial reactive dyes and Cu(II) from water
      in the absence and presence of complexing agents using chitosan were measured at
      30 degrees C. Three simplified kinetic models, i.e., pseudo-first-order, pseudo
      second-order, and intraparticle diffusion, were tested to investigate the
      adsorption mechanisms. It was shown that the adsorption of reactive dyes and
      Cu(II) in the absence of complexing agents could be best described by the
      intraparticle diffusion model, whereas that of Cu(II) in the absence of
      complexing agents such as EDTA, citric acid, and tartaric acid by the pseudo
      second-order equation. Kinetic parameters of the three models and the normalized
      standard deviations between the measured and predicted results were also
      calculated and discussed.

PMID- 11228958
TI  - Physiological and behavioral responses of stonefly nymphs to enhanced limestone
      treatment of acid mine drainage.
AB  - A new acid mine drainage (AMD) treatment system uses pulsed, fluidized beds of
      limestone, and carbon dioxide pretreatment of influent AMD, to enhance limestone
      neutralization of AMD. We conducted laboratory studies to evaluate the behavior
      and physiology of larval stoneflies (Pteronarcys proteus, Plecoptera) exposed to
      effluents produced by the treatment system. Survival, sodium balance, drift, and
      feeding responses by P. proteus to treated and untreated AMD were examined. P.
      proteus nymphs exhibited significant losses of whole body sodium in exposures to
      untreated AMD. Nymphs exposed to treated effluents experienced no loss of whole
      body sodium. Nymphs exposed to untreated AMD showed elevated drift rates and
      depressed feeding rates relative to those of nymphs exposed to treated AMD, and
      to AMD-free controls. No significant differences in feeding or drift behavior
      occurred between nymphs exposed to treated effluents and those exposed to AMD
      free controls. The treatment system, with and without CO2 pretreatment, provided
      water that was not toxic to the test animals, and that allowed normal behavioral
      and physiological function.

PMID- 11228959
TI  - Effects of recycled FGD liner material on water quality and macrophytes of
      constructed wetlands: a mesocosm experiment.
AB  - We investigated the use of flue-gas-desulfurization (FGD) by-products from
      electric power plant wet scrubbers as liners in wetlands constructed to improve
      water quality. Mesocosm experiments were conducted over two consecutive growing
      seasons with different phosphorus loadings. Wetland mesocosms using FGD liners
      retained more total and soluble reactive phosphorus, with lower concentrations in
      the leachate (first year) and higher concentrations in the surface water (second
      year). Leachate was higher in conductivity (second year) and pH (both years) in
      lined mesocosms. Surface outflow did not reveal any significant difference in
      physicochemical characteristics between lined and unlined mesocosms. There was no
      significant difference in total biomass production of wetland plants between
      lined and unlined mesocosms although lower average stem lengths and fewer stems
      bearing flowers were observed in mesocosms with FGD liners. Potentially
      phytotoxic boron was significantly higher in the belowground biomass of plants
      grown in lined mesocosms with low phosphorus loading. A larger-scale, long-term
      wetland experiment close to full scale is recommended from this two-year mesocosm
      study to better predict the potentially positive and negative effects of using
      FGD by-products in constructed wetlands.

PMID- 11228960
TI  - The hydroxide-assisted hydrolysis of cyanogen chloride in aqueous solution.
AB  - The hydrolysis of cyanogen chloride (ClCN) was studied as a function of
      temperature and pH. Results were used to resolve discrepancies among previously
      reported kinetic constants. The pH dependence was studied over a range of 9.54
      10.93 at a temperature of 21.0 degrees C. The effect of temperature was
      investigated over the range of 10-30 degrees C at a pH of approximately 10.
      Changes in the concentrations of ClCN and the reaction products cyanic acid and
      chloride ion were monitored with time. For the conditions corresponding to these
      experiments, the hydroxide-assisted hydrolysis pathway predominated. Collision
      frequency factor and activation energies recommended to represent the hydrolysis
      of ClCN in aqueous solution are A = 2.06 x 10(11) M-1 s-1 and Ea = 60,980 J mol-1
      for the hydroxide-ion-assisted reaction, and A = 9.97 x 10(8) s-1 and Ea = 87,180
      J mol-1 for the water-assisted reaction.

PMID- 11228961
TI  - Photochemical oxidation of arsenic by oxygen and iron in acidic solutions.
AB  - The rate of oxidation of As(III) to As(V) by oxygen is increased by several
      orders of magnitude by the presence of dissolved Fe(III) and illumination with
      near ultraviolet light. The oxidation reaction has been studied in acidic
      conditions in the absence and presence of dissolved oxygen. A reaction mechanism
      has been postulated in which Fe(III)-hydroxide and -chloride complexes first
      absorb photons to produce highly oxidising hydroxyl and dichloro radicals. A
      series of rapid competing reactions involving free radicals then occur in which
      As(III) is oxidised via the As(IV) intermediate. The observed arsenic oxidation
      rate is controlled by the rate of photon absorption and the fraction of As(IV)
      which undergoes oxidising rather than reducing reactions. The use of iron
      compounds as a photo-oxidant is advantageous because Fe(III) hydroxide
      precipitate is an excellent adsorbent for As(V).

PMID- 11228962
TI  - Nitrous oxide production in high-loading biological nitrogen removal process
      under low COD/N ratio condition.
AB  - Effects of influent COD/N ratio on N2O emission from a biological nitrogen
      removal process with intermittent aeration, supplied with high-strength
      wastewater, were investigated with laboratory-scale bioreactors. Furthermore, the
      mechanism of N2O production in the bioreactor supplied with low COD/N ratio
      wastewater was studied using 15N tracer method, measuring of reduction rates in
      denitrification pathway, and conducting batch experiments under denitrifying
      condition. In steady-state operation, 20-30% of influent nitrogen was emitted as
      N2O in the bioreactors with influent COD/N ratio less than 3.5. A 15N tracer
      study showed that this N2O originated from denitrification in anoxic phase.
      However, N2O reduction capacity of denitrifiers was always larger than NO3(-)-N
      or NO2(-)-N reduction capacity. It was suggested that a high N2O emission rate
      under low COD/N ratio operations was mainly due to endogenous denitrification
      with NO2(-)-N in the later part of anoxic phase. This NO2(-)-N build-up was
      attributed to the difference between NO3(-)-N and NO2(-)-N reduction capacities,
      which was the feature observed only in low COD/N ratio operations.

PMID- 11228963
TI  - Ultrasonic irradiation of dichlorvos: decomposition mechanism.
AB  - The sonochemical degradation of dichlorvos in a batch reactor is investigated.
      Dichlorvos was irradiated with 500 kHz ultrasound at input powers ranging from 86
      to 161 W. Acoustic power and sparge gas are two factors which greatly affect
      sonochemical degradation efficiency. Increasing total acoustic power input from
      86 to 161 W resulted in a change in the rate constant from 0.018 +/- 0.001 min-1
      to 0.037 +/- 0.002 min-1. The change in rate constant due to sparge gas (Argon,
      Oxygen, and Argon/Oxygen (60/40% v/v) mixture) at a power of 161 W is also
      investigated, with the Argon/Oxygen mixture giving the highest rate constant
      (0.079 +/- 0.005 min-1). Total organic carbon and ion chromatographic analyses
      are employed to determine and quantify major degradation products, including
      dimethyl phosphate, formate, carbon dioxide, chloride, and phosphate. The extent
      of mineralization, indicated by a decrease in the total organic carbon, and the
      formation of the various intermediates and products, varies with saturating gas.
      A pathway for dichlorvos decomposition is proposed, based upon formation rates of
      the various intermediates and products and the rate of decrease of the total
      organic carbon in the system. The limiting steps in the mineralization pathway
      appear to be transformation of dimethyl phosphate and formate.

PMID- 11228964
TI  - Bacterial dynamics in the drinking water distribution system of Brussels.
AB  - Water samples and pipe coupons were collected from the Brussel's drinking water
      distribution system (DS). A treated surface water and various groundwaters feed
      this DS. Parameters related to bacterial regrowth have been measured on these
      samples: temperature, concentrations of free residual chlorine, concentration of
      biodegradable dissolved organic carbon (BDOC), abundance of suspended bacteria,
      densities of fixed bacteria and levels of bacterial activity. Results showed that
      groundwaters were less susceptible to favor bacterial regrowth in the DS pipes.
      Treated surface water and mixed waters had the highest potential of bacterial
      regrowth in the DS dead ends. Results also showed that the potential regrowth
      induced by the distribution of a treated surface water could be reduced if: (1)
      the BDOC levels were below 0.25 mg C/l at the outlet of the surface water
      treatment plant; (2) a significant free chlorine residual was present within the
      whole DS. Second-stage biological filtration using granular activated carbon is
      now under construction at the surface water treatment plant feeding a part of
      this DS. This treatment implementation should reduce BDOC levels and chlorine
      demand of the treated surface water and will further reduce the slight regrowth
      phenomena observed in this DS.

PMID- 11228965
TI  - Role of temperature, chlorine, and organic matter in copper corrosion by-product
      release in soft water.
AB  - Soft, low alkalinity drinking waters tend to cause relatively high copper
      corrosion by-product release in plumbing systems. Long-term tests (6-8 months) in
      a synthetic, microbially stable soft tap water confirmed that lower pHs and
      higher temperatures increased copper release to water. Soluble copper release
      increased at lower temperature and lower pH. Low levels of free chlorine (0.7
      mg/L) slightly increased copper release at pH 9.5, in marked contrast to the
      dramatic reductions in copper release that have been observed in soft waters in
      which Type III pitting corrosion is occurring. Gum xanthan and sodium alginate
      produced a microbially unstable water that reduced the pH and DO during
      stagnation in pipes--these indirect effects far outweighed their possible role in
      chelation or other modes of direct attack on copper surfaces.

PMID- 11228966
TI  - Simultaneous urea hydrolysis, formaldehyde removal and denitrification in a
      multifed upflow filter under anoxic and anaerobic conditions.
AB  - A multifed upflow filter (MUF), working under anoxic or anaerobic conditions,
      coupled with an aerobic biofilm airlift suspension (BAS) reactor was operated in
      order to treat a wastewater with high formaldehyde (up to 1.5 g L-1) and urea (up
      to 0.46 g L-1) concentrations. In the MUF, formaldehyde removal, denitrification
      and urea hydrolysis took place simultaneously. The MUF was operated at 37 degrees
      C, at a hydraulic retention time (HRT) ranging from 1 to 0.3 d. An organic
      loading rate (OLR) of 0.5 kg-formaldehyde m-3 d-1 was efficiently eliminated
      during anaerobic operation and transformed into methane, while a much higher OLR
      (up to 2 kg-formaldehyde m-3 d-1) was oxidised under anoxic conditions by the
      nitrite or nitrate from the nitrifying airlift. However, only 80% of urea was
      hydrolysed to ammonia in an anoxic environment while complete conversion occurred
      under anaerobic conditions. Moreover, formaldehyde concentrations higher than 50
      mg L-1 provoked a loss of efficiency of urea hydrolysis, decreasing to 10% at
      formaldehyde concentrations above 300 mg L-1. Methane production rate during the
      anaerobic stage was adversely affected by accumulations of formaldehyde in the
      reactor causing lower formaldehyde removal efficiency. However, denitrification
      proceeded properly even at a formaldehyde concentration of 700 mg L-1 in the
      reactor, although nitrous oxide appears in the off-gas. The COD/N ratios required
      for complete nitrite and nitrate denitrification with formaldehyde were estimated
      at 2.1 and 3.5 kg-COD/kg-N, respectively.

PMID- 11228967
TI  - Enhanced biodegradation of petrochemical wastewater using ozonation and BAC
      advanced treatment system.
AB  - The characteristics of degradation/conversion of bio-refractory and the growth of
      a biofilm are investigated in laboratory-scale pre-ozonation and lifted moving
      bed biological activated carbon (BAC) advanced treatment processes treating
      phenol, benzoic acid, aminobenzoic acid and petrochemical industry wastewater
      which contains acrylonitrile butadiene styrene (ABS). The optimal reaction time
      and ozone dosage of pre-ozonation for bio-refractory conversion were determined
      to be 30 min and 100-200 mg O3/hr, respectively. After pre-ozonation of 30 min
      treatment, BOD5/COD ratio of influent and effluent increased apparently from 20
      to 35%, approximately. However, the change of pH in pre-ozonation was
      inconspicuous. The optimal flow rate of influent and air were controlled at 1.6
      l/h and 120-150 nl/min in lifted moving-bed BAC advanced treatment reactor. A COD
      removal efficiency of 85-95% and 70-90% may be maintained by using an organic
      loading of 3.2-6.3 kg COD/m3 day and 0.6-1.6 kg-COD/m3 day with an HRT of 6.0 h
      as secondary and advanced treatment system, respectively. The time required for
      the BAC bed is be regenerated by a thermal regeneration is prolonged 4-5 times
      more than that of GAC system. It can be estimated that the enhanced COD removal
      capability of the biofilm was not only due to the increase in the COD removal
      capability of acclimated bacteria, but also due to species succession of bacteria
      in bio-film ecosystem.

PMID- 11228968
TI  - Spatial and temporal evolution of the levels of tritium in the Tagus River in its
      passage through Caceres (Spain) and the Alentejo (Portugal).
AB  - This work is the result of a collaboration between Spanish and Portuguese
      laboratories. The specific objective was to quantify the time evolution during
      1994, 1995 and 1996 of the radioecological impact of the liquid releases of 3H
      from the Almaraz Nuclear Power Plant (ANPP) in the section of the Tagus River
      corresponding to Caceres province in Spain and the Alentejo region in Portugal.
      We found that the temporal evolution of the levels of tritium depends on the
      management of the water held in the cooling reservoir of the ANPP and the
      presence of the dams that exist along the river. This management regime has a 12
      month period. Also the movement of the mass of tritiated water (HTO) downriver
      was much faster during 1996 than 1995 or 1994 due to the hydrological differences
      between those years and consequently to the different amounts of water
      transferred between the reservoirs of the dams. From the hypothesis that
      hydrodynamically it is impossible to differentiate tritiated water from non
      tritiated water, a model was constructed that satisfactorily reproduces the
      temporal evolution of the 3H in the zone of the Tagus River in which the exchange
      of water takes place, with the cooling reservoir of the Almaraz Nuclear Power
      Plant.

PMID- 11228969
TI  - Hydrogen-dependent denitrification in a two-reactor bio-electrochemical system.
AB  - An autotrophic biological process was developed for the treatment of nitrate
      contaminated drinking water. The system comprised of two steps: the water to be
      treated was first enriched with hydrogen (energy source) in the cathodic chamber
      of an electrochemical cell, and then denitrified in the bioreactor. The
      bioreactor was a packed bed of granulated activated carbon, and the water flow
      was directed in an upward continuous mode. The system was operated for one year,
      at various water velocities and current intensities. Denitrification rates up to
      0.25 kg N m-3 d-1 were obtained at the hydraulic residence time of 1 h. The
      system was stable. When detected in the effluent, the concentration of nitrite
      was low, even under conditions that resulted in the elution of very high
      concentrations of nitrate.

PMID- 11228970
TI  - Microcosms-experiments to assess the potential for natural attenuation of
      contaminated groundwater.
AB  - Groundwater samples from six wells of a former gas plant site were characterised
      using chemical, microbial and ecotoxicological methods. Degradation studies were
      performed in batch-culture under aerobic conditions with the groundwater samples
      containing their autochthonous microflora and original contaminant mixture. The
      highest O2-consumption (3 mmol 100 ml-1), combined with BTEX (8.3 mg l-1) and
      naphthalene (171.3 mg l-1) degradation, as well as formation of organic acids was
      found after N- and P-supplementation with the highest contaminated groundwater
      sample. The other highly polluted groundwater sample showed no activity obviously
      because of the toxicity of some compounds. The major part of the PAHs and BTEX
      was eliminated in the assays with the low contaminated groundwater samples. The
      results indicate that the microbial degradation capacity and thereby the natural
      attenuation capacity in each groundwater differ and cannot be assessed simply by
      chemical, microbial and toxicological data. Additionally activity tests with
      authentic groundwater samples with and without nutrient supplementation are
      recommended.

PMID- 11228971
TI  - Factors influencing lake recovery from eutrophication--the case of basin 1 of
      Lake Balaton.
AB  - Lake Balaton is a large, shallow, and calcareous lake that was subject to a rapid
      eutrophication during the 1970s. Management measures taken from the mid-1980s
      decreased the phosphorus load to the lake from 0.5 to 0.3 g P m-2 yr-1. Using
      long-term load and water quality data, we analyse the response of the formerly
      hypertrophic Basin 1 of the lake by the means of simple empirical models. Several
      factors that are commonly neglected during studies of lake recovery modified the
      apparent settling velocity of total P and consequently, the biomass of the
      phytoplankton. These factors included the loads of calcium and suspended solids,
      the loading ratio of the dissolved to particulate phosphorus, and blooming of the
      dominant cyanobacterium, Cylindrospermopsis raciborskii. Due to the rapid
      immobilisation of the mobile phosphorus in the surface sediments, moderate
      reduction (45-50%) in the external load resulted in a surprisingly fast and
      significant improvement of the water quality in the hypertrophic southwestern
      basins of the lake.

PMID- 11228972
TI  - Inter-relationship between adsorption and pH in peat biofilters in the context of
      a cation-exchange mechanism.
AB  - A mathematical model of biofiltration McNevin and Barford (1998) has been
      augmented to include speciation, acid/base equilibria and pH dependence of
      adsorptive equilibria. It accurately predicts qualitative aspects of dynamic
      transients observed in an experimental perfusion column and supported a mechanism
      of adsorption by cation exchange with acidic functional groups on the surface of
      peat. It mirrored the buffering capacity of peat when solutions of high and low
      pH flow over the peat surface. This is a direct result of cation exchange where
      adsorption of cations increases with pH. This buffering capacity makes peat an
      attractive medium for engineered biological systems which must often operate
      within narrow pH bands to optimise biological activity.

PMID- 11228973
TI  - Color and chlorinated organics removal from pulp mills wastewater using activated
      petroleum coke.
AB  - Delayed petroleum coke, a waste by-product from the oil sand industry, was
      utilized in the production of activated carbon. The activated carbon was then
      evaluated for color and chlorinated organics reduction from pulp mill wastewater.
      The activation of the petroleum coke was evaluated using a fixed bed reactor
      involving carbonization and activation steps at temperature of 850 degrees C and
      using steam as the activation medium. The activation results showed that the
      maximum surface area of the activated coke was achieved at an activation period
      of 4 h. The maximum surface area occurred at burnoff and water efficiency of 48.5
      and 54.3%, respectively. Increasing the activation period to 6 h resulted in a
      decrease in the surface area. Methylene blue adsorption results indicated that
      the activation process was successful. Methylene blue adsorbed per 100 g of
      applied activated coke was 10 times higher than that adsorbed by raw petroleum
      coke. Adsorption equilibrium results of the bleached wastewater and the activated
      coke showed that significant color, COD, DOC and AOX removal (> 90%) was achieved
      when the activated coke dose exceeded 15,000 mg/L. Adsorption isotherms, in terms
      of COD, DOC, UV and color were developed based on the batch equilibrium data.
      Based on these isotherms, the amount of activated coke required to achieve
      certain removal of color and AOX can be predicted. The utilization of the
      petroleum coke for the production of activated carbon can provide an excellent
      disposal option for the oil sand industry at the same time would provide a cheap
      and valuable activated carbon.

PMID- 11228974
TI  - Catalytic decomposition of the reactive dye Uniblue A on hematite. Modeling of
      the reactive surface.
AB  - Experimental results from the adsorption and subsequent catalytic combustion of
      the reactive dye Uniblue A on hematite indicate that this iron oxide can be used
      as an affordable catalyst for environmental purposes. Uniblue A was adsorbed on
      hematite and the products of the catalytic oxidation in O2 atmosphere were
      analyzed by thermal programmed gas-chromatography/mass spectrometry (STDS-GC-MS)
      analysis. The catalytic combustion of Uniblue A in the presence of hematite led
      to about 40% conversion of the dye C-content into CO2 at T = 275 degrees C. The
      activation energy (Ea) for the desorption of CO2 and other polyaromatic
      hydrocarbons (PAHs) from the hematite surface was determined to be 23.4 kcal mol
      1. Identification of the species of Uniblue A in solution and those existing on
      the hematite surface was carried out in the framework of the generalized two
      layer diffuse model. The modeling of the amount of dye absorbed on hematite is in
      good agreement with the experimental data.

PMID- 11228975
TI  - Modeling the two stages of surfactant-aided soil washing.
AB  - This paper provides new insights into modelling the distribution of hydrophobic
      compounds between soil and water phases in the presence of nonionic surfactant
      micelles. Experimental measurements were made of various systems comprising a non
      ionic surfactant, five soils of different fractional organic carbon contents, and
      a hydrophobic (disperse) dye. Soil-washing performance was quantified using
      reciprocal surfactant-soil solubilization coefficients (1/Kd). Two stages of
      partitioning were identified. In stage 1, the dye concentration increased
      slightly with increasing surfactant dose until surfactant monomers saturated the
      bulk solution at the critical micelle concentration (cmc). The washing
      performance was 1:1 proportional to the surfactant monomer concentration. Most of
      the surfactant in this stage is sorbed. In stage 2, above the cmc, soil-washing
      performance increased linearly with increasing available surfactant micelles in
      the bulk solution. Reciprocal surfactant-soil solubilization coefficients (1/Kd),
      octanol-water partition coefficients (Kow), fractional organic carbon content of
      the soil (foc), and surfactant concentration were correlated for each stage in
      the soil-washing process using two simple equations.

PMID- 11228976
TI  - A novel multi-electrode system for electrolytic and biological water treatments:
      electric charge transfer and application to denitrification.
AB  - A novel multi-electrode system is proposed for electrolytic and biological water
      treatments. The multi-electrode system is comprised of multiple working
      electrodes and their counter electrode, where electric current or potential
      applied to each electrode is controlled independently. Experimental result for
      different electrolyte solutions showed that electric charge in the system was
      efficiently carried by dissociative electrolytes such as carbonate ions. This
      transfer mechanism is regarded as being effective both in keeping pH level around
      neutrality and in passing certain amounts of electric current especially in
      dilute solutions such as groundwater and surface water. A long-term (over 500
      days) experiment also showed the enhanced and stable denitrification performance
      of biofilm-electrode reactor (BER) equipped with the multi-electrode system,
      comparing to former BERs. This superior performance was thought to be
      attributable to large effective surface area of electrode, the charge transfer
      mechanism by dissociative electrolyte, and the formation of highly reducing (or
      oxidizing) zones. From these results, we conclude that the multi-electrode system
      is useful for electrolytic and biological treatments of groundwater and surface
      water.

PMID- 11228977
TI  - The adsorption kinetics of metal ions onto different microalgae and siliceous
      earth.
AB  - In the present work the adsorption kinetics of the six metal ions aluminum, zinc,
      mercury, lead, copper, and cadmium onto living microalgae were measured. The
      freshwater green microalga Scenedesmus subspicatus, the brackish water diatom
      Cyclotella cryptica, the seawater diatom Phaeodactylum tricornutum, and the
      seawater red alga Porphyridium purpureum were the subject of investigation. In
      most cases the adsorption rate of the metals could be well described by using the
      equation of the Langmuir adsorption rate expression. Inverse parameter estimation
      allowed the determination of the rate constants of the adsorption process and the
      maximum metal content of the algae. The highest values for the rate constant were
      obtained for Porphyridium purpureum followed by Phaeodactylum tricornutum. High
      values for the maximum content were obtained for Cyclotella cryptica and
      Scenedesmus subspicatus. The maximum rate constant was 24.21 h-1 for the
      adsorption of Hg to Porphyridium purpureum whereas the maximum metal content
      (0.243 g g-1) was obtained for Zn on Cyclotella cryptica. A comparison of these
      values with those obtained for the mineral siliceous earth exhibiting low maximum
      content and high adsorption rates reveals that the mechanism of adsorption onto
      the algae is a mixture of adsorption and accumulation.

PMID- 11228978
TI  - Co-conditioning and dewatering of chemical sludge and waste activated sludge.
AB  - The conditioning and dewatering behaviors of chemical and waste activated sludges
      from a tannery were studied. Capillary suction time (CST), specific resistance to
      filtration (SRF), and bound water content were used to evaluate the sludge
      dewatering behaviors. Zeta potentials were also measured. Experiments were
      conducted on each sludge conditioned and dewatered separately, and on the sludge
      mixed at various ratios. Results indicate that the chemical sludge was relatively
      difficult to be dewatered, even in the presence of polyelectrolyte. When the
      waste activated sludge was mixed with the chemical sludge at ratios of 1:1 and
      2:1, respectively, the dewaterability of chemical sludge improved remarkably
      while the relatively better dewaterability of the waste activated sludge
      deteriorated only to a limited extent. As the mixing ratios became 4:1 and 8:1,
      the dewaterability of the mixed sludge was equal to that of the waste activated
      sludge. The optimal polyelectrolyte dosage for the mixed sludge was equal to or
      less than that of the waste activated sludge. It is proposed that the chemical
      sludges act as skeleton builders that reduce the compressibility of the mixed
      sludge whose dewaterability is enhanced. Bound water contents of sludge decreased
      at low polyelectrolyte dosage and were not significantly affected as
      polyelectrolyte dosage increased. Advantages and disadvantages of co-conditioning
      and dewatering chemical sludge and waste activated sludge were discussed.

PMID- 11228979
TI  - The impact of alum discharges on a natural tropical wetland in Uganda.
AB  - Alum sludge discharge effects on a natural wetland on the shores of Lake Victoria
      at Gaba in Uganda has been investigated. The water quality in the swamp, the
      sediment chemistry and plant growth and productivity were monitored. The
      subsequent application of alum sludge discharges shows no immediate, noticeable,
      adverse overall effects on the water quality and sediment chemistry. A distinct
      effect on plant productivity was noted in Cyperus papyrus L. the dominant
      macrophyte in the Gaba swamp resulting in a low productivity rate of 5.1 g/m2 d
      and the apparent phasing out of this macrophyte in the swamp. Phragmites
      mauritianus (Kunth) exhibited better tolerance to alum sludge. Clear indications
      are cited of the ecosystem degrading and cumulative effects being marked over a
      longer time frame.

PMID- 11228980
TI  - Composition, structure and size distribution of suspended particulates from the
      Rhine River.
AB  - Fluvial suspended particulates collected from the Rhine River were investigated
      in terms of composition, structure and size distribution. Elemental analysis and
      Diffuse Reflectance Infrared Spectroscopy reveal that most particulate organic
      matter is formed from material derived from microorganisms. Transmission Electron
      Microscopy observations on resin-embedded samples and structural characterization
      from break-up experiments, show that fluvial particulate matter should be viewed
      as fractal aggregates organized by bacterial exopolymeric substances. The shape
      of particulate size distribution suggests that the formation and dynamics of
      suspended particulate matter are controlled mainly by physical processes.
      Finally, particulate growth and structure are consistent with a cluster-cluster
      aggregation scheme.

PMID- 11228981
TI  - Effect of process configuration and substrate complexity on the performance of
      anaerobic processes.
AB  - The roles of substrate complexity (molecular size of the substrate) and process
      configuration in anaerobic wastewater treatment were investigated to determine
      optimal methanogenic technology parameters. Five substrates (glucose, propionate,
      butyrate, ethanol, and lactate) plus a mixed waste (60% carbohydrate, 34%
      protein, and 6% lipids) were studied under five reactor configurations: batch-fed
      single-stage continuous stirred tank reactor (CSTR), continuously fed single
      stage CSTR, two-phase CSTR, two-stage CSTR, and single-stage upflow anaerobic
      sludge blanket (UASB). The substrate feed concentration was 20,000 mg/L as COD.
      The solids retention time (SRT) and hydraulic retention time (HRT) in the CSTR
      reactors were 20 d, while HRT in the UASB was 2 d. All reactors were operated for
      at least 60 d (equal to 3SRT). Substrate complexity was observed to be less
      significant under two-phase, two-stage and UASB reactor configurations. Two-phase
      CSTR, two-stage CSTR, and single-stage UASB configurations yielded the lowest
      effluent chemical oxygen demands (130-550, 60-700, and 50-250 mg/L,
      respectively). The highest effluent chemical oxygen demands were detected when
      feeding glucose, propionate, and lactate to continuously fed single-stage CSTRs
      (10, 400, 9900, and 4700 mg/L COD, respectively) and to batch-fed single-stage
      CSTRs (11, 200, 2500, and 2700 mg/L COD, respectively). Ironically, the one stage
      CSTR--most commonly utilized in the field--was the worst possible reactor
      configuration.

PMID- 11228982
TI  - Coagulation mechanism of salt solution-extracted active component in Moringa
      oleifera seeds.
AB  - This study focuses on the coagulation mechanism by the purified coagulant
      solution (MOC-SC-PC) with the coagulation active component extracted from M.
      oleifera seeds using salt solution. The addition of MOC-SC-PC tap water formed
      insoluble matters. This formation was responsible for kaolin coagulation. On the
      other hand, insoluble matters were not formed when the MOC-SC-PC was added into
      distilled water. The formation was affected by Ca2+ or other bivalent cations
      which may connect each molecule of the active coagulation component in MOC-SC-PC
      and form a net-like structure. The coagulation mechanism of MOC-SC-PC seemed to
      be an enmeshment of Kaolin by the insoluble matters with the net-like structure.
      In case of Ca2+ ion (bivalent cations), at least 0.2 mM was necessary for
      coagulation at 0.3 mgC l-1 dose of MOC-SC-PC. Other coagulation mechanisms like
      compression of double layer, interparticle bridging or charge neutralization were
      not responsible for the coagulation by MOC-SC-PC.

PMID- 11228983
TI  - Phenanthrene desorption from soil in the presence of bacterial extracellular
      polymer: observations and model predictions of dynamic behavior.
AB  - The extracellular polymer produced by a bacterium isolated from soil was employed
      in laboratory studies of desorption of a model polynuelear aromatic hydrocarbon
      (PAH), phenanthrene. The experimental results show that the selected
      extracellular polymer enhances the extent of release of soil-bound phenanthrene.
      A kinetic model was developed as an aid in interpreting the alterations in
      phenanthrene desorption resulting from polymer addition. The model employs a
      statistical gamma (gamma) distribution to describe spectrum of rate constants for
      transfer of phenanthrene from soil to water, and assumes instantaneous binding of
      phenanthrene to polymer and of polymer to the test soil. The relevant
      distribution coefficients and statistical parameters of the gamma distribution
      needed for the model were evaluated in independent experiments. Using these
      measured parameters, the model provides a satisfactory independent prediction of
      phenanthrene release from soil to aqueous phase at two test polymer
      concentrations, 50 mg TOC/L and 100 mg TOC/L. The success of the independent
      model predictions suggests a mechanism for the influence of extracellular polymer
      on phenanthrene desorption. The intrinsic, soil-specific, rate constants for
      solid to solution transfer of phenanthrene do not appear to be changed by
      bacterial polymer. Instead, polymer binding of phenanthrene in solution results
      in an increase in driving force for desorption by decreasing the solution
      concentration of the free, unbound, PAH molecule.

PMID- 11228984
TI  - Nitrogen-alkalinity interactions in the highly polluted Scheldt basin (Belgium).
AB  - We present results of one year observations in highly heterotrophic and oxygen
      depleted rivers of the polluted Scheldt basin. Monthly measurements revealed a
      high variability for dissolved inorganic carbon and nitrogen, with the following
      strong parallelism: highest alkalinity and NH4+ were associated with lowest NO3-
      and oxygen and vice-versa. In river water incubations, nitrification lowered the
      alkalinity whereas denitrification raised it; in an anoxic, NO3(-)-free
      incubation an increase of alkalinity was observed, partially due to
      ammonification. A stoichiometric analysis, taking into account the amount of
      protons produced or consumed by each process involving nitrogen, revealed that
      monthly variations of NO3- and NH4+ with ammonification, nitrification and
      denitrification could explain the 28 and 62% alkalinity variations at all
      stations, except one. The remaining part of the alkalinity variations was
      attributed to other anaerobic processes (Mn-, Fe- and SO4-reductions). This trend
      seems to be the result of the whole catchment metabolism (riverine waters and
      sediments, sewage networks and agricultural soils). The observed HCO3-
      concentrations in the Scheldt basin were 2-10 times higher than the
      representative concentrations reported in pristine basins and used in chemical
      weathering models. This suggests the existence of an anthropogenic source,
      originating from organic matter decomposition. We conclude that in highly
      polluted basins, nitrogen transformations strongly influence the acid-base
      properties of water.

PMID- 11228986
TI  - Anaerobic pre-treatment of herbal-based pharmaceutical wastewater using fixed
      film reactor with recourse to energy recovery.
AB  - The concept of immobilization technology has been incorporated in this research
      study for biomethanation of high strength herbal based pharmaceutical wastewater.
      Accordingly, an investigation has been made on laboratory scale to assess the
      feasibility of an anaerobic fixed film fixed bed reactor system to pre-treat
      herbal-based pharmaceutical wastewater with recourse to energy recovery,
      including influence of operating conditions. The work was carried out with
      laboratory-scale upflow reactor, equipped with nylon scrubber as random support.
      The reactor was operated at 35 degrees C. COD removal efficiencies ranging from
      76 to 98% were achieved for organic loading rates upto 10 kgCOD/m3 d, while the
      highest organic loading rate (around 48 kg COD/m3 d) led to efficiencies of 46
      50%. The influences of hydraulic retention time and substrate concentration were
      also studied. The reactors did now show destabilization under impulse hydraulic
      and organic overloadings. Reactor stability was easily achieved under
      intermittent operation, with breaks, after which the reactors rapidly returned to
      their optimal performance.

PMID- 11228985
TI  - Surface properties of sludge and their role in bioflocculation and settleability.
AB  - The influence of sludge retention time (SRT) on the extracellular polymeric
      substances (EPS) and physicochemical properties (hydrophobicity and surface
      charge) of sludge was studied using laboratory-scale sequencing batch reactors
      (SBRs) fed a synthetic wastewater containing glucose and inorganic salts. Sludge
      surfaces were more hydrophobic (larger contact angle) and less negatively charged
      at higher SRTs (16 and 20 d) than at lower SRTs (4 and 9 d). The ratio of
      proteins to carbohydrates within the EPS of the sludges increased as the SRT
      increased from 4 to 12 d corresponding to the changes in the physicochemical
      properties of the sludge. The protein:carbohydrate ratio remained constant at
      SRTs of 16 and 20 d. A transition in sludge properties appeared to occur between
      the upper range of low- (9 d) and lower range of high-SRTs. The total EPS
      content, however, was independent of the SRT. A higher sludge volume index (SVI),
      an indication of poorer settleability or compression, was associated with a
      larger amount of total EPS but no significant correlation between SVI and the
      surface properties of sludge was observed. A more hydrophobic and less negatively
      charged surface corresponded to lower levels of ESS. These results indicate that
      it is the surface properties, hydrophobicity, surface charge and composition of
      EPS, of sludge, rather than the quantity of EPS, that govern bioflocculation. In
      contrast, the EPS content is more important in controlling the settleability of
      sludge.

PMID- 11228987
TI  - Colorimetric flow-injection analysis of dissolved iron in high DOC waters.
AB  - An iron flow-injection analysis system has been optimized for the analysis of
      iron in waters high in dissolved organic carbon. The method detects either
      dissolved iron(II) or total dissolved iron with a detection limit of 10 nM,
      precision of 0.65% at 1 microM, and a dynamic range of four orders of magnitude.
      There are minimal interferences (< 1%) from other metals at environmental
      concentrations. The iron(II) method measures iron(II) in the presence of excess
      iron(III) with less than 1% interference. When used with pre-acidified samples,
      the total dissolved iron method agrees well with electrothermal atomic absorption
      spectrometry for a variety of natural waters with a range of dissolved organic
      carbon (3-36 mg C/L) and iron (1-28 microM) concentrations. When used with
      samples at their ambient pH, the total dissolved iron method detects dissolved
      iron, but not colloidal iron (size fraction 0.05-0.45 micron).

PMID- 11228988
TI  - Heavy metal removal with Mexican clinoptilolite: multi-component ionic exchange.
AB  - This paper describes the interactions of Pb(II), Cd(II), and Cr(VI) competing for
      ion-exchange sites in naturally occurring clinoptilolite. Dissolved Pb and Cd
      were effectively removed within 18 h in batch reactors, with higher removal
      efficiencies (> 95%) in the acidic pH range. The presence of Cr(VI), which can
      interact with these metals to form anionic complexes, significantly diminished
      the Pb and Cd removal efficiencies. A decrease in the efficiency of
      clinoptilolite to remove Pb was also observed in the high (> or = 10) pH range.
      This was attributed to the formation of anionic hydroxo-complexes with little
      affinity for cationic ion exchange sites. Pb outcompeted Cd for ion exchange
      sites in a flow-through column packed with clinoptilolite (contact time = 10 s).
      The preferential removal of Pb in column, but not in batch reactors, reflects
      that competitive retention can be affected by contact time because diffusion
      kinetics may influence the removal efficiency to a greater extent than
      equilibrium partitioning. Phenol, which was tested as a representative organic co
      contaminant, slightly hindered heavy metal removal in batch reactors. This was
      attributed to the formation of organometallic complexes that cannot penetrate the
      zeolite exchange channels. Altogether, these results show that natural zeolites
      hold great potential to remove cationic heavy metal species from industrial
      wastewater. Nevertheless, process efficiency can be hindered by the presence of
      ligands that form complexes with reduced accessibility and/or affinity for ion
      exchange.

PMID- 11228989
TI  - Phenotypic and genotypic characterization of human and nonhuman Escherichia coli.
AB  - Estuarine waters receive fecal pollution from a variety of sources, including
      humans and wildlife. Escherichia coli is one of several fecal coliform bacteria
      that inhabit the intestines of many warm-blooded animals that sometimes
      contaminate water. Its presence does not specifically implicate human fecal
      input, therefore it is necessary to differentiate contamination sources to
      accurately assess health risks. E. coli were isolated from human sources (HS) and
      nonhuman sources (NHS) in the Apalachicola National Estuarine Research Reserve
      and analyzed for fatty acid methyl ester (FAME), O-serogroup, and pulsed-field
      gel electrophoresis (PFGE) profiles. For FAME and PFGE analyses, there was no
      relationship between profile and isolate source. Human source PFGE profiles were
      less diverse than NHS isolates, and conversely for FAME. In contrast, O
      serogrouping showed less diversity for HS vs. NHS isolates, and the predominant
      HS O-serogroups differed significantly (P < 0.01) from those of NHS isolates.

PMID- 11228991
TI  - Ammonium removal using a novel unsaturated flow biological filter with passive
      aeration.
AB  - A novel vertical bed process for the removal of ammonium from secondary
      effluents, using a "passive air pump", has been developed. The process is based
      on convective aeration caused by a fill and draw operational sequence, and
      combines the advantages of the vertical wetlands concept with the high loading
      rates typically associated with trickling filters. Experiments were carried out
      in a 500-l reactor using simulative effluents and actual municipal secondary
      effluents. A maximal ammonium removal rate of 1100 g N/m2 reactor/d was achieved
      using simulative effluents and an effective gravel size of 0.96 mm. At all
      hydraulic loads applied, the nitrification rate was found to be limited by the
      oxygen transfer rate. The small-size medium used with simulative effluents
      clogged when using actual municipal secondary effluents. Two other media (2.46 mm
      and 4.31 mm) did not clog during the entire experimental period and a maximum
      removal load of 300 g N/m2 reactor/d was achieved. This value is still much
      higher than typical rates reported for conventional vertical beds.

PMID- 11228990
TI  - Oxidation of p-hydroxybenzoic acid by Fenton's reagent.
AB  - Fenton's reagent has been shown to be a feasible technique to treat phenolic-type
      compounds present in a variety of food processing industry wastewaters. A model
      compound, p-hydroxybenzoic acid was oxidised by continuously pumping two
      solutions of ferrous iron and hydrogen peroxide. Typical operating variables like
      reagent feeding concentrations and flowrate, temperature and pH were studied. A
      mechanism of reactions based on the classical Fenton's chemistry was assumed, and
      computed concentration profiles of the parent compound, ferrous ion and
      dihydroxybenzene were compared to experimental results. The model qualitatively
      predicted the influence of several operating variables, however, calculated
      results suggested the presence of parallel routes of substrate elimination and/or
      a initiating rate constant with a higher value. The low efficiency of a well
      known hydroxyl radical scavenger (tert-butyl alcohol) also supports the
      contribution of oxidising species different from the hydroxyl radical to
      substrate removal. Further evidence of the presence of reactions different from
      the hydroxyl radical oxidation was observed from comparison of the simultaneous
      Fenton's or UV/H2O2 oxidations of p-hydroxybenzoic acid, tyrosol and p-coumaric
      acid.

PMID- 11228992
TI  - Isolation and characterization of coagulant extracted from Moringa oleifera seed
      by salt solution.
AB  - It is known that M. oleifera contains a natural coagulant in the seeds. In our
      previous research, the method using salt water to extract the active coagulation
      component from M. oleifera seeds was developed and compared with the conventional
      method using water. In this research, the active coagulation component was
      purified from a NaCl solution crude extract of Moringa oleifera seeds. The active
      component was isolated and purified from the crude extract through a sequence of
      steps that included salting-out by dialysis, removal of lipids and carbohydrates
      by homogenization with acetone, and anion exchange. Specific coagulation activity
      of the active material increased up to 34 times more than the crude extract after
      the ion exchange. The active component was not the same as that of water extract.
      The molecular weight was about 3000 Da. The Lowry method and the phenol-sulfuric
      acid method indicated that the active component was neither protein nor
      polysaccharide. The optimum pH of the purified active component for coagulation
      of turbidity was pH 8 and above. Different from the conventional water extracts,
      the active component can be used for waters with low turbidity without increase
      in the dissolved organic carbon concentration.

PMID- 11228993
TI  - Simultaneous methanogenesis and denitrification of pretreated effluents from a
      fish canning industry.
AB  - A lab-scale hybrid upflow sludge bed-filter (USBF) reactor was employed to carry
      out methanogenesis and denitrification of the effluent from an anaerobic
      industrial reactor (EAIR) in a fish canning industry. The reactor was initially
      inoculated with methanogenic sludge and there were two different operational
      steps. During the first step (Step I: days 1-61), the methanogenic process was
      carried out at organic loading rates (OLR) of 1.0-1.25 g COD l-1 d-1 reaching COD
      removal percentages of 80%. During the second step (Step II: days 62-109) nitrate
      was added as KNO3 to the industrial effluent and the OLR was varied between 1.0
      and 1.25 g COD l-1 d-1. Two different nitrogen loads of 0.10 and 0.22 g NO3(-)-N
      l-1 d-1 were applied and these led to nitrogen removal percentages of around 100%
      in both cases and COD removal percentages of around 80%. Carbon to nitrogen ratio
      (C:N) in the influent was maintained at 2.0 and eventually it was increased to
      3.0, by means of glucose addition, to control the denitrification process. From
      these results it is possible to establish that wastewater produced in a fish
      canning industry can be used as a carbon source for denitrification and that
      denitrifying microorganisms were present in the initially methanogenic sludge.
      Biomass productions of 0.23 and 0.61 g VSS:g TOC fed for Steps I and II,
      respectively, were calculated from carbon global balances, showing an increase in
      biomass growth due to denitrification.

PMID- 11228994
TI  - Evaluation of two concentration methods for detecting Giardia and Cryptosporidium
      in water.
AB  - The cartridge filtration method and membrane filtration method based on the
      fluorescent antibody procedure were evaluated for their recovery efficiencies and
      detection limits of Giardia and Cryptosporidium. We assessed the performances of
      the two concentration methods for water samples collected from Taiwan water
      treatment plants. The membrane filtration method was characterized by higher
      recovery rate and detection limit comparing with the cartridge filtration method.
      The occurrences of both parasites, and the relationships of parasite
      concentrations with indicator microorganisms show inconsistency between the two
      methods. It was discovered that water turbidity reduced the recovery
      efficiencies, and raised the detection limits for both parasites regardless of
      the method used.

PMID- 11228995
TI  - Colour removal from a simulated dye wastewater using a two-phase anaerobic packed
      bed reactor.
AB  - In recent years, rapid technological advances in the textile and dyeing industry
      have yielded benefits to society but have also generated new and significant
      environmental problems. The treatment alternatives applicable for the removal of
      colour vary, depending upon the type of dye wastewater. A synthetic, simulated
      mixed dye waste (Basic Yellow 28, Basic Yellow 21, Basic Red 18.1, Basic Violet
      Red 16, Basic Red 46, Basic Blue 16, Basic Blue 41) representing a known waste
      from a fibre production factory, was investigated. The biological process of
      anaerobic digestion has been recognised as a simple and energy-efficient means of
      treating and stabilising a wide range of organic industrial wastewaters. This
      study sets out to demonstrate the effect of different loading rates, dye
      concentrations and hydraulic retention times (HRTs) on colour removal efficiency
      under mesophilic anaerobic conditions. The reactor was operated under mesophilic
      conditions at different organic loading rates (OLRs) and HRTs for nine months.
      The results of this study show that a 2-stage mesophilic anaerobic up-flow packed
      bed reactor can remove up to 90% of the colour from a mixed cationic dye
      containing 1000 mg/l of dye. Colour removal efficiency falls as the influent dye
      concentration increases, but rises with increased hydraulic retention time and
      increased organic loading. The primary colour removal mechanism was one of
      biosorption with subsequent biodegradation. Acetoclastic methanogens were
      moderately inhibited at low organic loading rates of 0.25 kg COD/m3 d, at which
      level, acidogenesis and acetogenesis appeared to be unaffected. Inhibition of
      acidogenesis became marked at higher OLRs (1 kg COD/m3 d) and when the HRT was
      reduced from 5 to 3 days.

PMID- 11228996
TI  - Development of nitrification inhibition assays using pure cultures of
      Nitrosomonas and Nitrobacter.
AB  - Restricted requirements for nitrogen reduction at wastewater treatment plants
      have increased the need for assays determining the inhibition of nitrification.
      In this paper, two new assays studying ammonia oxidation and nitrite oxidation,
      respectively, are presented. As test organisms, pure cultures of Nitrosomonas and
      Nitrobacter isolated from activated sludge are used. The assays are performed in
      test tubes where the bacteria are incubated with the compound or wastewater to be
      tested. The nitrification rate is measured during 4 h and compared with reference
      samples. The test organisms were characterised with respect to temperature, pH
      and cell activity. Optimum temperature was 35 degrees C for Nitrosomonas and 38
      degrees C for Nitrobacter; optimum pH was 8.1 for Nitrosomonas and 7.9 for
      Nitrobacter. There was a linear relationship between the nitrification rate and
      the cell concentration in the studied interval. The cell activity decreased
      slightly with storage time. A significant level of inhibition was calculated to
      11% for the Nitrosomonas assay, and to 9% for the Nitrobacter assay. The assays
      are applicable to determination of nitrification inhibition in samples of
      industrial waste waters or influents of treatment plants, or chemical substances
      likely to be found in wastewater.

PMID- 11228997
TI  - Uncertainties in risk assessment for the determination of drinking water
      pollutant concentrations: Cryptosporidium case study.
AB  - There is a growing acknowledgement of the need to recognise uncertainties in the
      estimation of waterborne risks. In this paper, the strength of the science
      available to characterise Cryptosporidium risks in drinking water is
      investigated, in particular the determination of oocyst concentrations at various
      points in the chain of water supply. A recently developed scientific quality
      audit framework is used as a tool to guide this investigation. The framework
      systematically reveals the relatively greater strength of the science for the
      "upstream" elements (estimation of concentrations in environmental reservoirs)
      than for the "downstream" elements (concentrations in distribution). It is the
      downstream elements that have greater bearing on human health and public policy
      issues. It is noted that the adoption of new monitoring Regulations is likely to
      prompt action to strengthen knowledge of these downstream elements in the future.

PMID- 11228998
TI  - Hydrolysis of triphosphate from detergents in a rural waste water system.
AB  - The concentrations of detergent phosphates in raw sewage entering a small,
      predominantly domestic waste water treatment facility were determined using an
      ion chromatographic-flow injection analysis technique. Hourly loads of detergent
      phosphates were measured between 0600 and 2300 hrs (the major flow period in the
      plant) on days of both low and high phosphorus loads. The calculated loads of
      detergent phosphorus entering the plant on low and high load days were 260 g
      P/day and 350 g P/day, respectively. The half-life of detergent phosphates
      (triphosphate) in waste waters was measured to be 7.3 hours at 15 degrees C and
      3.0 h at 20 degrees C. The major factor contributing to triphosphate degradation
      in waste water was shown to be biological in nature, with the most likely
      mechanism being enzymatic hydrolysis.

PMID- 11228999
TI  - Removal of a synthetic organic chemical by PAC-UF systems--I: Theory and
      modeling.
AB  - Based on the age distributions of powdered activated carbon (PAC) in reactors,
      the competitive bi-solute isotherm and the pore-surface diffusion mechanism, a
      model was developed to predict the removal of a trace synthetic organic chemical
      (SOC) when PAC was applied to an ultrafiltration (UF) membrane system.
      Independent experiments evaluated the input parameters for the model. The pore
      diffusion in liquid-filled pore was the dominant internal mass transfer mechanism
      in a PAC particle and the surface diffusion mechanism was neglected in the model.
      Model prediction was compared with data from pilot plant experiments treating
      simazine in natural water. Due to the blending and the increasing PAC in the UF
      loop, a transient behavior of effluent simazine concentration was observed in the
      UF effluent. The model predicted successfully this periodical variation of the
      simazine concentration in the UF loop effluent, as well as the simazine
      concentration in the effluent from the PAC slurry contactor. The faithful model
      prediction required the modeling of the phenomenon of adsorption/desorption of an
      SOC on membrane itself.

PMID- 11229000
TI  - Removal of a synthetic organic chemical by PAC-UF systems. II: Model application.
AB  - This paper describes several application potentials with a recently developed
      model for predicting the synthetic organic chemical (SOC) removal by powdered
      activated carbon (PAC) adsorption during ultrafiltration (UF) and discusses the
      removal mechanism. The model was successfully applied, without any modification,
      to dead-end mode operation as well as to cross-flow mode operation, validating
      the assumption of the internal diffusion control mechanism and the continuously
      stirred-tank-reactor (CSTR) concept. Even when UF was operated in a cross-flow
      mode, PAC added was re-circulating in suspension for only a short time. Then,
      solute uptake took place mostly by PAC immobilized in membrane tubes not only for
      dead-end operation but also for cross-flow operation. Therefore, cross-flow
      operation did not have any advantage regarding the SOC mass transfer on PAC in UF
      loop over dead-end operation. The model simulation implied that pulse PAC
      addition at the beginning of filtration cycle resulted better SOC removal than
      continuous PAC addition. However, for the pulse PAC addition mode, the model
      predicted somewhat lower effluent SOC concentration than the observed values, and
      the benefit of pulse PAC application in terms of reducing SOC over its continuous
      dosage was not confirmed. Longer detention time of PAC dosed in a pulse than
      continuously dosed PAC could possibly further decrease internal diffusivity.

PMID- 11229001
TI  - Novel method for enhancing permeate flux of submerged membrane system in two
      phase anaerobic reactor.
AB  - A two-phase anaerobic reactor system with a submerged membrane in the acidogenic
      reactor was designed for the enhancement of organic acid conversion and methane
      recovery. A submerged membrane system in a two-phase anaerobic reactor was tested
      to increase the sludge retention time (SRT) of acidogen and to enhance the solid
      separation. The pilot plant experiment was performed for piggery wastewater
      treatment for a year. The membrane material used was mixed esters of cellulose of
      0.5 micron pore size. COD removal efficiency was 80% and the methane production
      showed 0.32 m3/kg COD removed for the submerged membrane system in the anaerobic
      digester. As the cake resistance of the membrane caused a serious problem, a
      stainless-steel prefilter and air backwashing methods were applied to minimize
      the cake resistance effectively. Among the tested prefilters, the 63 microns pore
      prefilter showed the best performance for reducing cake resistance and a
      successful long-term operation. By cleaning with alkali first and acidic
      solutions later, the permeate flux decreased by long-term operation was recovered
      to 89% of that with a new membrane.

PMID- 11229002
TI  - Adsorption of sodium lauryl sulfate onto arsenic-bearing ferrihydrite.
AB  - Ferrihydrite is an excellent adsorbent for binding trace toxic contaminants such
      as arsenic, and precipitate flotation of the arsenic-bearing ferrihydrite has
      been studied. Anionic surfactants such as sodium lauryl sulfate (SLS) and sodium
      oleate (NaOL) are suitable collectors for the flotation. The adsorption of SLS
      both alone and after the subsequent addition of NaOL on these precipitates at pH
      4-5 was measured. It has been shown that the synergistic effect of the two
      surfactants on flotation is dependent on their addition order. The presence of
      NaOL before SLS in the conditioning stage can prevent the adsorption of SLS
      because of the electrostatic shielding of adsorption sites on the precipitates.
      The post addition of NaOL to the SLS-bearing precipitates can promote the
      flocculation of the precipitates and enhance entrainment of SLS for better
      flotation. The SLS adsorption data fit better with the modified Frumkin isotherm
      than the Langmuir isotherm. Thermodynamic parameters (-delta Gads0,delta Hads0,
      and delta Sads0) have been derived from the analysis of the adsorption isotherms.
      The results suggest that the adsorption of SLS on AFH is physical and exothermic.

PMID- 11229003
TI  - Treatment of a foul condensate from Kraft pulping with horseradish peroxidase and
      hydrogen peroxide.
AB  - Foul condensates originating from the Kraft recovery process contain phenolic
      compounds whose removal might render these process streams more useful for reuse
      in other plant operations or more amenable to biological degradation. Treatment
      of a foul condensate with horseradish peroxidase and H2O2 selectively targeted
      phenolic compounds resulting in a reduction of the total phenols concentration
      below 1 mg/L as well as a substantial toxicity drop as measured using the
      Microtox assay; however, only marginal COD removal was achieved. Comparisons of
      treatments between synthetic wastewaters and real wastewaters to which phenol
      were added revealed that the condensate contained species that protect the enzyme
      from inactivation by reaction products. Analytical data as well as experimental
      results suggest that these species are lignin derivatives.

PMID- 11229004
TI  - Adsorption mechanism of hexavalent chromium by redox within condensed-tannin gel.
AB  - We have proposed a new recovery system of hexavalent chromium Cr(VI) that is of
      great toxicity utilizing condensed-tannin gels derived from a natural polymer
      with many polyhydroxyphenyl groups. The adsorption mechanism of Cr(VI) to the
      tannin molecules was clarified. The adsorption mechanism consists of four
      reaction steps; the esterification of chromate with tannin molecules, the
      reduction of Cr(VI) to trivalent chromium Cr(III), the formation of carboxyl
      group by the oxidation of tannin molecules and the ion exchange of the reduced
      Cr(III) with the carboxyl and hydroxyl groups. It was found in this recovery
      system that a large amount of proton was consumed accompanied with the reduction
      of Cr(VI) so that the acidic solution containing Cr(VI) was transferred
      automatically to neutral one by choosing an appropriate initial pH. The carboxyl
      group which was created by the oxidation of tannin molecules parallel to the
      reduction of Cr(VI) to Cr(III) contributed to an increase in the ion-exchange
      sites of the reduced Cr(III). The maximum adsorption capacity of Cr(VI) reached
      287 mg Cr/g dry tannin gel under the conditions of 0.77 water content of tannin
      gel and the initial pH = 2. This adsorption capacity was five to ten times higher
      than that obtained by the ion exchange between ordinary Cr(III) and tannin
      molecules for the tannin gels prepared under similar conditions. The system
      proposed here will provide an important information on a zero-emission-oriented
      process because it has such advantages as higher adsorption capacity of chromium
      and lower volume of secondary wastes compared with conventional process.

PMID- 11229005
TI  - The fate and transport of mercury, methylmercury, and other trace metals in
      Chesapeake Bay tributaries.
AB  - Six tributaries to the Chesapeake Bay were analyzed for suspended particulate
      matter, dissolved organic carbon, particulate organic carbon, mercury,
      methylmercury, lead, nickel, zinc, cadmium, chromium, and copper. This study
      examined the importance of flow regime, suspended particulate concentration, and
      watershed characteristics on the transport of mercury, methylmercury, and other
      trace metals. Total mercury concentrations were higher under high flow conditions
      which is consistent with the tendency of this metal to bind strongly to
      particulate matter. Methylmercury showed less flow rate dependence. Nickel, lead,
      and zinc concentrations responded strongly to flow rate on the Potomac River,
      while weaker correlations were found on the other rivers sampled. Cadmium,
      copper, and chromium concentrations were the least influenced by flow. Partition
      coefficients calculated in this study were similar to those of other estuaries
      and overall decreased in the order of Hg > Ni-MMHg > Cr-Pb-Zn > Cd > Cu.
      Watershed yield estimates and associated retention factors were calculated for
      the various rivers. These calculations showed that for most of the rivers,
      mercury was the most strongly retained within the watershed.

PMID- 11229006
TI  - Dynamic pesticide removal with activated carbon fibers.
AB  - Rapid small-scale minicolumn tests were carried out to simulate the atrazine
      adsorption in water phase with three pelletized pitch-based activated carbon
      fibers (ACF) and one commercial granular activated carbon (GAC). Initial atrazine
      solutions were prepared with pretreated ground water. Minicolumn tests showed
      that the performance of highly activated carbon fibers (surface area of 1700
      m2/g) is around 7 times better than the commercial GAC (with surface area at
      around 1100 m2/g), whereas carbon fibers with medium activation degree (surface
      area of 1500 m2/g) had a removal efficiency worse than the commercial carbon. The
      high removal efficiency of the highly activated ACF is due to the wide-opened
      microstructure of the material, with an appreciable contribution of the low size
      mesopores, maintaining at these conditions a fast kinetic adsorption rate rather
      than a selective adsorbent for micropollutants vs. natural organic matter.

PMID- 11229007
TI  - Contribution of different sources to the pollution of wet weather flows in
      combined sewers.
AB  - Experiments performed on "Marais" catchment, in central Paris, aimed to follow up
      the quality of wet weather flows from the entry to the exit of a combined sewer
      network. SS, VSS, COD, BOD5, Cd, Cu, Pb, Zn concentrations were measured for an
      important number of rain events in roof, yard, street runoff, as well as in dry
      and wet weather flows at the catchment outlet. Mass entry-exit totals, at the
      scale of the catchment, were calculated over 31 rain events in order to evaluate
      the contribution of different types of runoff, of sanitary sewage and of sewer
      sediments to the total wet weather pollutant loads at the catchment outlet. The
      erosion of in-sewer pollutant stocks was found to be the main source of particles
      and of organic matter in wet weather flows, whereas heavy metal loads mainly
      originated from roof runoff, due to the corrosion of metallic roofs. Particles
      eroded inside the sewer during rain events were found to be quite different from
      the particles constituting the main part of sewer sediments: they are organic and
      biodegradable, with rather important settling velocities and seem to accumulate
      during dry weather periods. A change of the chemical form of heavy metals was
      noticed during the transport in the sewer and it is suspected that a fraction of
      the dissolved metals from the runoff is adsorbed on sewer sediments.

PMID- 11229008
TI  - Removal of Cu(II) and Cd(II) from aqueous solution by seafood processing waste
      sludge.
AB  - Dried waste slurry generated in seafood processing factories has been shown to be
      an effective adsorbent for the removal of heavy metals from dilute solutions.
      Characterization of the sludge surface with scanning electron microscope and X
      ray microanalyzer were carried out to evaluate the components on the sludge
      surface that are related to the adsorption of metal ions. Aluminum and calcium,
      as well as organic carbon are distributed on the surface of sludge. Alkalimetric
      titration was used to characterize the surface acidity of the sludge sample. The
      surface acidity constants, pKa1s and pKa2s, were 5.80 and 9.55, respectively.
      Batch as well as dynamic adsorption studies were conducted with 10(-5) to 5 x 10(
      3) M Cu(II) and Cd(II). A surface complexation model with the diffuse layer model
      successfully predicted Cu(II) and Cd(II) removals in single metal solutions.
      Predictions of sorption in binary-adsorbate systems based on single-adsorbate
      data fits represented competitive sorption data reasonably well over a wide range
      of conditions. The breakthrough capacity found from column studies was different
      for each metal ion and the data reflect the order of metal affinity for the
      adsorbent material very well.

PMID- 11229009
TI  - Potential of freezing in wastewater treatment: soluble pollutant applications.
AB  - When wastewater containing only soluble pollutants is frozen gradually, ice
      crystals grow from the pure water only, while pollutants are rejected into the
      liquid phase thus increasing their concentration. In this way, pure water can be
      removed from various wastewaters. Two kinds of wastewater were studied: synthetic
      wastewater containing water and one or more soluble pollutants, and industrial
      wastewaters (urban wastewater and cutting oil wastewater). In most cases,
      separation efficiency close to 100% was achieved. A large range of pollutant
      concentrations was studied in order to determine the limits of freezing
      separation.

PMID- 11229010
TI  - A new RT-PCR method for the identification of reoviruses in seawater samples.
AB  - The frequent occurrence of reoviruses in environmental samples could be a
      potential source of interference with enterovirus detection, especially when
      enterovirus isolation on cell culture is required. In order to evaluate new virus
      based criteria for enforcing recreational water quality standards, a new method
      based on a broad reverse transcribed polymerase chain reaction (RT-PCR) was set
      up to detect reoviruses. Two primers were engineered to amplify a 538 base pair
      fragment of the Sigma 2 gene. Reovirus strains obtained from ATCC (Jones, Lang,
      Dearing, Abney, NC-TEV, SV59 and SV12) were used as references. Twenty-four
      samples of 101 were collected from two beaches of the Adriatic sea and 12 from
      the neighbourhood of Fano Harbour Channel. The presence of environmental
      reoviruses was tested on both concentrated seawater samples and lysates of BGM
      cells infected with the concentrated seawater samples. The new method was used in
      parallel with the detection of a 3:3:4 electrophoretic pattern of reovirus RNA in
      polyacrylamide gel electrophoresis (PAGE). Enterovirus and bacteria were also
      screened in compliance with EEC directives. No enteroviruses were isolated, and
      it was not attributable to reovirus interference. All the reovirus found by PAGE
      (8/72) were confirmed by RT-PCR, while several genomes (14/72) were detected only
      by RT-PCR. Presumptive methods of virus identification, that is CPE on BGM cells
      and haemagglutination test, were not able to detect them. The specificity of RT
      PCR products was checked by direct nucleotide sequence analyses of the amplicons.
      The phylogenetic analyses showed heterogeneous taxa including human and animal
      reoviruses, with strong evidence that they were spreading consistently from the
      Harbour-Channel. This novel approach for reovirus detection will be very useful
      as a trace route of faecal pollution; more importantly, it could be very useful
      in contributing to the creation of a databank of circulating enteric viruses.

PMID- 11229011
TI  - Toxicity of benzotriazole and benzotriazole derivatives to three aquatic species.
AB  - Benzotriazole and its derivatives comprise an important class of corrosion
      inhibitors, typically used as trace additives in industrial chemical mixtures
      such as coolants, deicers, surface coatings, cutting fluids, and hydraulic
      fluids. Recent studies have shown that benzotriazole derivatives are a major
      component of aircraft deicing fluids (ADFs) responsible for toxicity to bacteria
      (Microtox). Our current research compared the toxicity of benzotriazole (BT), two
      methylbenzotriazole (MeBT) isomers, and butylbenzotriazole (BBT). Acute toxicity
      assays were used to model the response of three common test organisms: Microtox
      bacteria (Vibrio fischeri), fathead minnow (Pimephales promelas) and water flea
      (Ceriodaphnia dubia). The response of all the three organisms varied over two
      orders of magnitude among all compounds. Vibrio fischeri was more sensitive than
      either C. dubia or P. promelas to all the test materials, while C. dubia was less
      sensitive than P. promelas. The response of test organisms to unmethylated
      benzotriazole and 4-methylbenzotriazole was similar, whereas 5
      methylbenzotriazole was more toxic than either of these two compounds. BBT was
      the most toxic benzotriazole derivative tested, inducing acute toxicity at a
      concentration of < or = 3.3 mg/l to all organisms.

PMID- 11229012
TI  - Contamination of vinyl chloride in shallow urban rivers in Osaka, Japan.
AB  - Vinyl chloride (VC) contamination had taken place in heavily polluted shallow
      rivers (Taishogawa and lower Hiranogawa Rivers) in Osaka, Japan. VC
      concentrations ranged from below detection limit to 55.6 micrograms l-1 (mean:
      3.35 micrograms l-1, standard deviation: 5.96 micrograms l-1). Of 55 volatile
      organic compounds (VOCs) analyzed, concentrations of cis-1,2-dichloroethene (c
      DCE), tetrachloroethene (PCE) and trichloroethene (TCE) were significantly
      correlated to VC concentrations in the rivers, indicating that they share common
      sources. The four VOCs were invariably present at approximate relative ratios of
      about 1:2.7:1.5:0.31 (VC: c-DCE: PCE: TCE). The similarity between sampling dates
      in the distribution pattern of the four VOCs concentrations were observed, but
      their concentrations were different between the dates. The concentrations of the
      four VOCs decreased with distance down the river. A sample from the upper
      Taishogawa River in July 1997 had 55.6 micrograms l-1 of VC, 152 micrograms l-1
      of c-DCE, 86.2 micrograms l-1 of PCE and 18.4 micrograms l-1 of TCE,
      respectively. These values are about an order of magnitude higher than the other
      sites over the study period and are likely indicative of point source inputs.

PMID- 11229013
TI  - The treatment and reuse of wastewater in the textile industry by means of
      ozonation and electroflocculation.
AB  - Two different oxidation treatments, ozonation and electroflocculation, were
      experimented on a pilot scale to test their efficiency in removing polluting
      substances from wastewaters of textile industries. Both pilot plants used
      reproduced very closely a full-scale treatment in order to obtain indications
      about the feasibility of a transfer on industrial scale. By means of ozone
      treatment very high colour removal (95-99%) was achieved and treated waters were
      reused satisfactorily in dyeing even with light colours. This evidence despite
      the fact that the chemical oxygen demand of treated waters was still in a range
      (75-120 mg/l, a decrease up to 60%) that was usually considered to be too high
      for recycling purposes, especially for dyeing light colours. Treating plants
      working at the above-mentioned conditions should guarantee low operating costs. A
      biological pre-treatment and a sand filtration are absolutely essential. The
      transfer on industrial scale of the treatment is currently under development
      under an already financed European project. Electrochemical treatment showed to
      be very efficient in removing colour (80-100%) and chemical oxygen demand (70
      90%). Moreover, a sensible decrease of chloride and sulphate ions was detected.
      Removal of flocculated material (post-treatment) must be, however, perfected in
      order to establish a correct costs-to-benefits ratio and therefore, propose an
      implementation of the technique on an industrial scale.

PMID- 11229014
TI  - Comment on "Chemical-biological treatment of pyrene" by Y. Zeng, P. K. A. Hong
      and D. A. Warrek, Water Research 34(4), 1157-1172 (2000).

PMID- 11229016
TI  - Synthesis and characterization of tris(bipyridyl)ruthenium(II)-modified mono-, di
      , and trinuclear manganese complexes as electron-transfer models for photosystem
      II.
AB  - With the aim of modeling the arrangement of redox-active and photoactive
      components along the electron-transfer pathway of photosystem II, tetra- to
      nonanuclear transition metal complexes have been synthesized, comprising one,
      two, or three manganese ions, oxidizable phenolates, and tris(2,2'
      bipyridyl)ruthenium(II)-type units as photosensitizers. These model complexes are
      considered to be mononuclear ([LnMn](PF6)m), dinuclear ([L1aMnIV2(mu-O)2](PF6)6),
      or trinuclear ([LnMnIIMnIIMnIILn](PF6)12) with respect to the number of manganese
      centers present. Electronic coupling between the manganese ions is strongly
      antiferromagnetic in the case of the di(mu-oxo)-dimanganese compound [L1aMnIV2(mu
      O)2](PF6)6, where the "ligand" [H2L1a]4+ consists of two
      tris(bipyridyl)ruthenium(II)-type units covalentely bound to a bismacrocyclic
      Me2dtne backbone to which the manganese ions are coordinated via an additional
      phenolate oxygen (Me2dtne = 1,2-bis(4-methyl-1,4,7-triazacyclononyl)ethane). Weak
      antiferromagnetic coupling is observed in compounds [LnMnIIMnIIMnIILn](PF6)12,
      where the three metals are in a linear arrangement (face-sharing octahedral).
      They are bridged by three phenolate oxygens of each of the deprotonated "ligands"
      [H3Ln]6+, respectively. Each ligand [H3Ln]6+ (n = 1, 2) consists of a tacn ring
      with three pendent arm phenols which are each bound to a
      tris(bipyridyl)ruthenium(II)-type unit (tacn = 1,4,7-triazacyclononane). In these
      compounds several electron-transfer steps were detected by electrochemical
      methods which are assigned to different redox processes located at individual
      electrochemically active components (Mn, Ru, bipyridyl, phenolate). For example,
      in the "mononuclear" compounds [LnMn](PF6)m (n = 1 or 2) Mn(II), Mn(III), and
      Mn(IV) are accessible and three Ru(II) centers are reversibly oxidized to
      Ru(III), and in addition, the coordinated phenolate can be oxidized to a highly
      reactive, coordinated phenoxyl radical. In several cases very slow heterogeneous
      electron-transfer rates were observed for redox processes involving the manganese
      centers.

PMID- 11229017
TI  - Novel and versatile reactions of trifluoroamine oxide: a new route to
      polyfluorinated ethers.
AB  - A series of pyrimidine methyl and polyfluoroalkyl ethers were synthesized from
      the reactions of trifluoroamine oxide (1) with several 5-substituted uracils in
      the presence of tetrabutylammonium hydroxide and methanol, 2,2,2-trifluoroethanol
      (6), or 1H,1H-pentafluoropropanol (7). With 5-(trifluoromethyl)uracil (2), the
      new ethers formed were 5-fluoro-5-(trifluoromethyl)-6-methoxypyrimidine-2,4-dione
      (8), 5-fluoro-5-(trifluoromethyl)-6-(trifluoroethoxy)pyrimidine-2,4-dione (9),
      and 5-fluoro-5-(trifluoromethyl)-6-(1H,1H- pentafluoropropoxy)pyrimidine-2,4
      dione (10). With 5-chlorouracil (3), the new ethers 5-chloro-5-fluoro-6
      methoxypyrimidine-2,4-dione (11), 5-chloro-5-fluoro-6-(trifluoroethoxy)pyrimidine
      2,4-dione (12), and 5-chloro-5-fluoro-6-(1H,1H-pentafluoropropoxy)pyrimidine-2,4
      dione (13) were obtained. With 5-fluorouracil (4), the new ethers 5,5-difluoro-6
      methoxypyrimidine-2,4-dione (14), 5,5-difluoro-6-(trifluoroethoxy)pyrimidine-2,4
      dione (15) and 5,5 difluoro-6-(1H,1H-pentafluoropropoxy)pyrimidine-2,4-dione (16)
      were found. By reaction of 5-nitrouracil (5), the new ethers 5-nitro-5-fluoro-6
      methoxypyrimidine-2,4-dione (17), 5-nitro-5-fluoro-6-(trifluoroethoxy)pyrimidine
      2,4-dione (18), and 5-nitro-5-fluoro-6-(1H,1H-pentafluoropropoxy)pyrimidine-2,4
      dione (19) were obtained. Each of the new compounds was characterized by using
      IR, 19F and 1H NMR, and mass spectroscopy, and elemental analysis. A single
      crystal X-ray diffraction study of 8 was helpful in confirming compound
      structure.

PMID- 11229018
TI  - Gold(I) and silver(I) metallocryptates based on 2,9-bis(diphenylphosphino)-1,8
      naphthyridine.
AB  - In acetonitrile the rigid diphosphine ligand 2,9-bis(diphenylphosphino)-1,8
      naphthyridine (dppn) reacts with (SMe2)AuCl in the presence of NaPF6 to produce a
      pale-yellow material identified as [Au2Na(mu-dppn)3](PF6)3 (1). In acetonitrile
      dppn reacts with 2 equiv of (SMe2)AuCl to form the simple Au-Cl adduct of the
      ligand, Au2Cl2dppn (2). In a fashion analogous to that of the synthesis of 1, the
      reaction of equimolar AgNO3 with dppn produces the trimetallic species [Ag2(mu
      dppn)3Ag](PF6)3 (3) as a bright-yellow material. 1, 2, and 3 were characterized
      by 31P(1H) NMR spectroscopy, electronic absorption spectroscopy, X-ray
      crystallography, emission spectroscopy, and elemental analysis. Additionally 1
      was further characterized by cyclic voltammetry and mass spectrometry.
      1.4.5CH3CN.0.5(C2H5)2O (C107H72Au2F18N10.5NaO) crystallizes in the triclinic
      space group P1 with a = 15.408(3) A, b = 17.295(3) A, c = 22.425(5) A, alpha =
      73.68(1) degrees, beta = 77.32(1) degrees, gamma = 74.18(1) degrees, V =
      5451.4(19) A3, and Z = 2. C32H24Au2Cl2N2P2 (2) crystallizes in the monoclinic
      space group Cc with a = 10.936(2) A, b = 19.860(5) A, c = 20.864(2) A, beta =
      118.182(1) degrees, V = 3127.3(8) A3, and Z = 4. Compound 3 crystallizes as the
      bis-DMSO adduct (C101H84Cl2F18N6O2P9S2) in the monoclinic space group C2/c with a
      = 28.825(7) A, b = 17.013(3) A, c = 23.916(7) A, beta = 115.23(1) degrees, V =
      10609.6(44) A3, and Z = 4. The structures of 1 and 3 contain a three-coordinate
      metal capping the metallocryptate with an encapsulated ion. The central Ag(I) ion
      in 3 is positioned off-center to form a short Ag...Ag interaction of 3.145(2) A,
      while the central Na+ ion of 1 is centrally positioned with long Au...Na
      interactions of approximately 3.5 A. The solution-state properties of 1 were
      probed. 1 is emissive, as are the Li, K, and Cs analogues.

PMID- 11229019
TI  - Comparative spectroscopic and electrochemical properties of
      bis(octakis(dodecylthio)naphthalocyaninato)europium(III) and bis(tetra-tert
      butylnaphthalocyaninato)europium(III) complexes.
AB  - Bis(substituted-2,3-naphthalocyaninato)europium(III) complexes:
      bis(octakis(dodecylthio)-2,3-naphthalocyaninato)europium(III) (Eu[2,3
      Nc(SC12H25)8]2, 1) and bis(tetra-tert-butyl-2,3- naphthalocyaninato)europium(III)
      (Eu[2,3-Nc(t-Bu)4]2, 2) have been synthesized by cyclic tetramerization of
      naphthalonitriles with Eu(acac)3.H2O in the presence of 1,8
      diazabicyclo[5.4.0]undec-7-ene (DBU) in refluxing n-octanol. These compounds were
      characterized by UV-visible, magnetic circular dichroism (MCD), near-IR, IR, EPR,
      and mass spectroscopies. The absorption and MCD spectra of 1 showed splitting of
      the Q band, with peaks at 700 and 784 nm, red shifted from the Q band of 2 at 763
      nm. The absorption and MCD spectral band deconvolution calculations of complex 1
      gave two A terms in the Q-band region. The A terms are assigned to 2A2-->2E1
      transitions. Cyclic voltammograms of 1 and 2 showed reversible oxidation couples
      at E1/2 = -0.28 V (for 2) and -0.25 V (for 1) vs ferrocenium/ferrocene (Fc+/Fc).
      The second oxidation exhibited a complicated behavior for both complexes. The
      reduction couples for 2 were observed at E1/2 = -0.61, -1.64, -1.97, and -2.42 V,
      and for 1 they were observed at E1/2 = -0.62, -1.60, -1.86, and -2.27 V vs
      Fc+/Fc. Spectral changes observed on chemical oxidation and reduction of the
      complexes are presented, and the behaviors of 1 and 2 are compared.

PMID- 11229020
TI  - Site-specific vanadates Co4Fe3.33(VO4)6 and Mn3Fe4(VO4)6.
AB  - Single crystals of Co4Fe3.33(VO4)6 and Mn3Fe4(VO4)6 were grown from equivalent
      CoO/Fe2O3/V2O5 and MnO/Fe2O3/V2O5 melts, respectively. The former crystallizes in
      the orthorhombic space group Pnma with parameters a = 4.965(1) A, b = 10.211(1)
      A, c = 17.188(3) A, and Z = 2 and is a homeotype of such catalysts as Mg2.5VMoO8.
      The latter crystallizes in the triclinic space group P1 with parameters a =
      6.703(2) A, b = 8.137(1) A, c = 9.801(2) A, alpha = 105.56(1) degrees, beta =
      105.58(2) degrees, gamma = 102.35(1) degrees, and Z = 1 and is a homeotype of
      beta-Cu3Fe4(VO4)6, the low-pressure form of alpha-Cu3Fe4(VO4)6. The cobalt
      analogue deviates in stoichiometry from the reactant melt to form the more dense
      alpha-Cu3Fe4(VO4)6 structure type comprised of partially occupied face-sharing
      octahedral and trigonal prismatic coordination sites.

PMID- 11229021
TI  - Metal-assisted unusual hydroxylation at the carbon atom of the triazine ring in
      dinuclear ruthenium(II) and osmium(II) complexes bridged by 2,4,6-tris(2-pyridyl)
      1,3,5-triazine: synthesis, structural characterization, stereochemistry, and
      electrochemical studies.
AB  - The reaction of cis-[M(bpy)2Cl2] (M = Ru(II), and Os(II) with 2,4,6-tris(2
      pyridyl)-1,3,5-triazine (tptz) in refluxing ethanol-water resulted in the
      formation of dinuclear complexes of the composition [(M(bpy)2)2(tptz
      OH)](PF6)3.nH2O (n = 1 for Ru and n = 0 for Os). In this reaction an unusual
      metal-induced hydroxylation at the carbon atom of the triazine ring of bridged
      tptz occurred. However, hydroxylation did not occur in the corresponding
      mononuclear complexes under similar reaction condition. A comparative study
      revealed that sufficient electrophilicity on the carbon atom and free movement of
      the attached pyridyl ring promoted the hydroxylation reaction. The hydroxylated
      dinuclear complexes exist in two stereoisomeric forms, a rac form (delta
      delta/lambda lambda) and a meso form (delta lambda/lambda delta). Both
      diastereoisomers have been isolated in pure form and characterized. The molecular
      structures of the rac form of Ru(II) complex (3-II) and meso form of the Os(II)
      complex (4-I) have been established by single-crystal X-ray studies. Crystal
      data: complex 3-II, monoclinic, C2/c, a = 24.584(7) A, b = 14.309(4) A, c =
      41.044(13) A, beta = 92.84(2) degrees, V = 14420.0(7) A3, Z = 8, R = 0.179, wR2 =
      0.479; complex 4-I, triclinic, P1, a = 13.444(7) A, b = 14.576(5) A, c =
      19.641(7) A, alpha = 98.21(3) degrees, beta = 101.67(4) degrees, gamma =
      105.80(4) degrees, V = 3546.0(3) A3, Z = 2, R = 0.093, wR2 = 0.279. The poor data
      quality of 3-II did not allow anisotropic refinement of non-hydrogen atoms except
      Ru and P. A PLUTO drawing of this compound is given only to support the molecular
      structure. 1H NMR data have been used to characterize the diastereoisomers. The
      dinuclear complexes exhibit unusual electrochemical behavior; cathodic shifts of
      the metal-centered oxidations and ligand-based first reduction compared to
      mononuclear complexes have been observed. There is a splitting in the metal
      centered oxidation potentials, indicating strong electronic communication between
      the metal centers. Comproportionation constants (Kcom) of the mixed-valence
      species have been calculated; the values are in the range 6.03 x 10(4)-4.7 x
      10(6). It appears that a metal-metal interaction occurred by an electron-transfer
      mode across the low-lying pi* orbital of the bridged tptz.

PMID- 11229023
TI  - Stereochemical activity of the metal-centered lone electron pair in group 14
      metallocenes. Crystal structure of the linear sandwich complex [C5(iPr)3H2]2Pb.

PMID- 11229022
TI  - Binuclear 1,2,4,5-tetraimino-3,6-diketocyclohexane
      bis[bis(bipyridine)ruthenium(II)] redox series.
AB  - The reaction of the [Ru(bpy)2(MeOH)2]2+ cation (bpy = 2,2'-bipyridine) with
      1,2,4,5-tetraaminobenzene in the presence of trace water and oxygen yields the
      cation [(bpy)2Ru(1,2,4,5-tetraimino-3,5-diketocyclohexane)Ru(bpy)2]4+. This
      binuclear species undergoes ligand-based reductions, giving the 3+ and 2+ charged
      species. The X-ray structure, electrochemistry, ZINDO calculations, and NMR, ESR,
      UV/vis, and IR spectra were analyzed where possible, giving an electronic model
      of the binuclear species and some of its redox products. The X-ray structure
      reveals the [(bpy)2Ru] fragments symmetrically disposed across the 1,2,4,5
      tetraimino-3,5-diketocyclohexane bridge in a molecule with Cs symmetry.

PMID- 11229024
TI  - Hyperfine tensors of [bis(maleonitriledithioleato)nickel]-.

PMID- 11229025
TI  - Control of structural ordering in crystalline lamellar aluminophosphates with
      periodicity from 51 to 62 A.

PMID- 11229026
TI  - Metal alkoxides as versatile precursors for group 4 phosphonates: synthesis and X
      ray structure of a novel organosoluble zirconium phosphonate.
AB  - Reactions of Ph2P(O)(OH) and t-BuP(O)(OSiMe3)(OH) with Ti(O-i-Pr)4 in equimolar
      ratios gave titanium phosphonates of the type [(O-i-Pr)3Ti(mu-O)2PR1R2]2 (1, R1 =
      R2 = Ph; 2, R1 = t-Bu, R2 = OSiMe3) as colorless crystalline solids in moderate
      yields. Reactions of Ph2P(O)(OH) and the isopropoxides of zirconium and hafnium
      resulted in products of the composition [(O-i-Pr)3M(mu-O-i-Pr)2(mu-OPOPh2)M(O-i
      Pr)2]Ph2P(O)(OH) (M = Zr (3), Hf (4)) in high yields. The compounds were
      characterized by 1H, 31P, and 29Si NMR, infrared (IR), and mass spectroscopic
      (MS) techniques. The molecular structures of 2 and 3 were confirmed by X-ray
      crystallography.

PMID- 11229027
TI  - Synthesis and characterization of 8-(dimethylamino)-1-naphthyl derivatives of
      aluminum, gallium, and indium.
AB  - The group 13 dichlorides of formula Ar'MCl2 [Ar' = 8-(dimethylamino)-1-naphthyl
      (8-(Me2N)C10H6)], M = Al (1), Ga (2), and In (3), have been prepared via the salt
      elimination reaction of 1 equiv of Ar'Li with MCl3 in toluene solution at -78
      degrees C. The reaction of 1 with LiAlH4 in diethyl ether solution at -78 degrees
      C produced the dihydride [Ar'AlH2]2 (4). The X-ray crystal structures of 1-4 have
      been determined and show that 1 and 2 are monomeric while 3 and 4 are dimeric in
      the solid state. The reaction of 1 with RLi in toluene solution at -78 degrees C
      results in ligand redistribution and formation of Ar'2AlR (R = Me (5), t-Bu (6)).
      The chloride analogue of 5 and 6, Ar'2AlCl (7), can be prepared directly from the
      reaction of 2 equiv of Ar'Li with AlCl3 in toluene solution at -78 degrees C. The
      homoleptic derivative Ar'3Al (8) was obtained when 3 equiv of Ar'Li was employed.
      Crystal data for 1: monoclinic, space group P2(1), a = 6.534(1) A, b = 10.801(1)
      A, c = 9.631(2) A, beta = 105.57(2) degrees, V = 654.8(2) A3, Z = 2, R = 0.0453.
      Crystal data for 2: monoclinic, space group P2(1), a = 6.552(2) A, b = 10.833(2)
      A, c = 9.601(2) A, beta = 106.05(2) degrees, V = 654.9(3) A3, Z = 2, R = 0.0609.
      Crystal data for 3: monoclinic, space group P2(1)/c, a = 7.401(2) A, b = 15.746
      A, c = 10.801(4) A, beta = 92.37(3) degrees, V = 1257.6(7) A3, Z = 2, R = 0.0712.
      Crystal data for 4: monoclinic, space group P2(1)/c, a = 13.343(2) A, b =
      11.228(2) A, c = 7.505(1) A, beta = 100.64(1) degrees, V = 1105.0(4) A3, Z = 4, R
      = 0.0560.

PMID- 11229028
TI  - Carbidohexarhenate cluster cores bicapped by mercury with acetate or thiolate
      ligands.
AB  - The reaction of [PPh4]3[Re7C(CO)21] (1) with 1 or more equiv of Hg(OAc)2 in
      dichloromethane provides the monomercury derivative [PPh4]2[Re7C(CO)21HgOAc] (2)
      in high yield. However, in the presence of methanol the reaction of 1 with 2
      equiv of Hg(OAc)2 yields the dimercury hexarhenium cluster compound
      [PPh4]2[Re6C(CO)18(HgOAc)2] (3) together with the dirhenium complex
      [PPh4][Re2(CO)6(mu-OMe)2(mu-OAc)] (4). The dimercury compound 3 reacts with
      various thiols HS-Z to form thiolate-substituted derivatives
      [PPh4]2[Re6C(CO)18(HgSZ)2] [Z = C6H4Br (5); C5H4N (6); C2H4COOH (7)]. All new
      compounds have been characterized by a combination of analytical and
      spectroscopic data, and the molecular structures of compounds 3-6 have been
      determined by X-ray crystallography.

PMID- 11229029
TI  - Structure, bonding, and dipole moment of (CH3)3N-SO3. A microwave study.
AB  - Six isotopic derivatives of the complex (CH3)3N-SO3 have been studied in the gas
      phase by microwave spectroscopy. The N-S bond length is 1.912(20) A, and the NSO
      angle is 100.1(2) degrees. The dipole moment, determined from Stark effect
      measurements, is 7.1110(69) D, representing an enhancement of 6.5 D over the sum
      of the dipole moments of the free monomers. Analysis of the 14N nuclear hyperfine
      structure indicates that about 0.6 e is transferred from the nitrogen to the SO3
      upon formation of the complex. Comparison between the gas-phase structure and
      that previously determined for the adduct in the solid state reveals small but
      significant differences, indicating that the formation of the dative bond is
      slightly less advanced in the gas. Gas-phase and solid-state structural data are
      compared for several related amine-SO3 systems.

PMID- 11229030
TI  - Solid-state 25Mg NMR study of inner-sphere Mg2+ binding complexes.

PMID- 11229032
TI  - Influence of DNA on the rate of ligand substitution in platinum(II) terpyridine
      complexes.
AB  - The kinetics of substitution of pyridine or 2-methylpyridine, by iodide or
      thiourea, in the complexes [Pt(4'-R'terpy)(2-Rpy)](BF4)2 (R' = o-tolyl or H; R =
      H or CH3) has been studied, at 25 degrees C, pH 7, and various ionic strength
      values, in the presence of and without calf thymus DNA. The reactions occur in
      one observable step, and plots of kobsd against nucleophile concentration give
      straight lines with zero intercepts. DNA inhibits all the reactions studied
      without altering the rate law; the second-order rate constants k2 decrease
      systematically on increasing DNA concentration and are larger at higher ionic
      strength values. Partitioning of the ionic reactants in solution on electrostatic
      grounds can account for this kinetic effect in the reaction with iodide. Iodide
      is kept off the double helix proximity while the dicationic complexes concentrate
      on it. The inhibiting effect observed for the uncharged reagent thiourea can be
      related to the specific binding mode of the complexes to DNA. The complexes
      studied are effective intercalators to double helix, and this type of
      interaction, which prevents attack of thiourea at platinum, decreases their
      actual concentration in solution. The inhibiting effect is larger for
      [Pt(terpy)(py)]2+ that is a better intercalator. Likewise, the decrease in the
      rate of substitution of 2-Rpy, at a given [DNA] on decreasing ionic strength, is
      due to the influence of ionic strength on the complex-DNA interactions.

PMID- 11229031
TI  - Redox pathways in DNA oxidation: kinetic studies of guanine and sugar oxidation
      by para-substituted derivatives of oxoruthenium(IV).
AB  - The oxidation of nucleotides and DNA by a series of complexes based on
      Ru(tpy)(bpy)O2+ (1) was investigated (tpy = 2,2':6',2"-terpyridine; bpy = 2,2'
      bipyridine). These complexes were substituted with electron-donating or
      withdrawing substituents in the para positions of the polypyridyl ligands so that
      the oxidation potentials of the complexes were affected but the reaction
      trajectory of the oxo ligand with DNA was the same throughout the series. The
      prepared complexes were (with E1/2(III/II) and E1/2(IV/III) values in volts
      versus Ag/AgCl) Ru(4'-EtO-tpy)(bpy)O2+ (2; 0.47, 0.60), Ru(4'-Cl-tpy)(bpy)O2+ (3;
      0.55, 0.63), Ru(tpy)(4,4'-Me2-bpy)O2+ (4; 0.48, 0.62), and Ru(tpy)(4,4'-Cl2
      bpy)O2+ (5; 0.58, 0.63). The complexes oxidized deoxycytosine 5'-monophosphate at
      the sugar moiety (k = 0.24-0.47 M-1 s-1) and guanosine 5'-monophosphate at the
      base moiety (k = 6.1-15 M-1 s-1). The rate constants increase across these ranges
      in the order 3 > 1 > 4 > 2, which is the same order as the redox potentials of
      the complexes. The effect of the base on these reactions was also studied, and
      xanthine was found to react with 1 much faster than guanine while hypoxanthine
      was less reactive than the sugar moiety. The complexes all oxidized
      oligonucleotides to generate base-labile lesions at guanine and a combination of
      spontaneous and base-labile scission at the sugar functionalities. The
      selectivity of cleavage in duplex and single-stranded DNA was not a strong
      function of the substituents on the metal complex.

PMID- 11229033
TI  - High-pressure synthesis of a new silicon clathrate superconductor, Ba8Si46.
AB  - A new silicon clathrate compound with a composition of Ba8Si46 was prepared under
      high-pressure and high-temperature conditions. The compound was isomorphous with
      Na8Si46 and became a superconductor with a transition temperature of 8.0 K.
      Barium atoms occupy all of the Si20 and Si24 cages of the clathrate structure.
      This is the first clathrate superconductor obtained as a bulk phase.

PMID- 11229034
TI  - Syntheses and spectroscopic and structural characterization of molybdenum(VI)
      citrato monomeric raceme and dimer, K4[MoO3(cit)].2H2O and
      K4[(MoO2)2O(Hcit)2].4H2O.
AB  - Investigation of the aqueous coordination chemistry for citrate and
      molybdenum(VI) resulted in the isolation of molybdenum(VI) citrato monomeric
      raceme and dimer K4[MoO3(cit)].2H2O (1) and K4[(MoO2)2O(Hcit)2].4H2O (2) (H4cit =
      citric acid). Complex 1 can serve as the first structurally characterized
      monomeric citrato molybdate and may represent an early mobilized precursor in the
      biosynthesis of FeMo-co (FeMo-cofactor). The two complexes have been
      characterized by elemental analyses and IR and NMR spectroscopies. The IR and NMR
      spectra are consistent with a monomeric species or a monooxo-bridged dinuclear
      structure, as revealed by a single crystal X-ray diffraction study. Compound 1 is
      monoclinic space group P2(1)/c with a = 7.225(1) A, b = 9.151(2) A, c = 22.727(2)
      A, beta = 94.93(1) degrees, V = 1497.1(7) A3, and Z = 4. Full-matrix least
      squares refinement resulted in residuals of R = 0.027 and Rw = 0.032. The
      molybdenum atom forms an octahedral coordination with three oxo groups and one
      tridentate citrate, in which the latter is coordinated through the alkoxy and
      vicinal carboxyl and much more weakly by one of the two terminal groups [2.411(3)
      A]. Compound 2 is triclinic space group P1 with a = 8.2728(8) A, b = 8.9514(8) A,
      c = 10.0605(9) A, alpha = 101.673(8) degrees, beta = 100.672(7) degrees, gamma =
      112.938(7) degrees, V = 642.5(3) A3, and Z = 1. Full-matrix least-squares
      refinement resulted in residuals of R = 0.033 and Rw = 0.039. The complex anion
      contains a linear (O2Mo)O(MoO2) core with the bridging oxo group lying at the
      center of inversion symmetry (Mo-Ob-Mo, 180 degrees). Each citrate ligand is
      three-coordinated to one molybdenum atom through the deprotonated hydroxy, alpha
      carboxyl, and one beta-carboxyl group, making each metal atom six-coordinate.

PMID- 11229035
TI  - Chemistry of the rhenium-azopyridine family: an oxo parent and derivatives
      thereof including a novel oxo-imido dimer.
AB  - The concerned azo ligands are 2-(phenylazo)pyridine (HL) and 2-((p
      chlorophenyl)azo)pyridine (ClL). The reaction of KReO4 with HL in hot
      concentrated HCl is attended with metal reduction and ligand chlorination
      affording the oxo complex ReVOCl3(ClL), 2, which furnishes ReIII(OPPh3)Cl3(ClL),
      3, upon treatment with PPh3. Aromatic amines, ArNH2, convert 2 to the imido
      complex ReV(NAr)Cl3(ClL), 5, and the unusual oxo-imido dimer (ClL)
      Cl2(O)ReVOReV(NAr)Cl2(ClL), 7. The complex ReIII(OPPh3)Cl3(HL), 4, has been
      generated from ReVOCl3(PPh3)2 and HL. Reaction of 4 with HL has yielded
      ReV(NPh)Cl3(HL), 6, via azo splitting. The complexes have been characterized with
      the help spectral, magnetic, and X-ray structural data (2, 3, 5c (Ar = pClC6H4)
      and 7.CH2Cl2 (Ar = pMeC6H4)). In 2, 3, and 5c the ReCl3 fragment is meridionally
      disposed, and in 7 the ReCl2 fragments have a trans configuration. The Re-O(oxo)
      bond, 1.663(6) A, in 2 and Re-N(imido) bond, 1.719(5) A, in 5c are triple bonds.
      The corresponding bonds are slightly longer in 7 wherein the (O)Re(1)-O(2)
      Re(2)(NAr) bridge is angular (151.0(5) degrees) and unsymmetrical, the Re(1)-O(2)
      bond, 1.849(7) A, having a large double-bond character (Re(2)-O(2), 1.954(7) A).
      In effect, cis-ReVO2 acts as a monodentate oxygen ligand toward ReVNAr in 7. In
      all cases the pyridine nitrogen binds trans to the oxo, OPPh3, or NAr donor. Bond
      length data are consistent with the presence of substantial d(Re)-pi*(azo) back
      bonding. In acetonitrile solution the complexes display electrochemical one
      electron metal (ReVI/ReV or ReIV/ReIII) and azo redox. The imido ligand in 5
      stabilizes the ReVI state (E1/2 approximately 1.4 V) better than the oxo ligand
      in 2 (approximately 1.9 V). Parallely it is more difficult to reduce the azo
      group in 5 (approximately -0.4 V) than in 2 (approximately 0.0 V). In 7 the metal
      (approximately 1.0 V) and azo (approximately -0.4 V) couples correspond to the
      imido and oxo halves, respectively. The significantly higher (by 0.2-0.6 V) metal
      reduction potentials of the azopyridine compared to pyridine-2-aldimine complexes
      is ascribed to the superior pi-acidity and electron-withdrawing character of the
      azo function relative to the aldimine function. This also makes the transfer of
      the ReVO oxygen function much more facile under azopyridine chelation as in 2.
      For the same reason, ReOCl3(PPh3)2 reacts with HL affording only 4 while it
      reacts with pyridine-2-aldimines furnishing oxo species. Crystal data for the
      complexes are as follows: 2, empirical formula C11H8Cl4N3ORe, crystal system
      triclinic, space group P1, a = 7.118(4) A, b = 8.537(4) A, c = 13.231(9) A, alpha
      = 79.16(5) degrees, beta = 78.03(5) degrees, gamma = 70.96(4) degrees, V =
      737.2(7) A3, Z = 2; 3, empirical formula C29H23Cl4N3OPRe, crystal system
      monoclinic, space group P2(1)/n, a = 11.264(2) A, b = 15.221(3) A, c = 17.628(4)
      A, beta = 94.21(3) degrees, V = 3014(1) A3, Z = 4; 5c, empirical formula
      C17H12Cl5N4Re, crystal system triclinic, space group P1, a = 9.683(3) A, b =
      10.898(3) A, c = 11.522(3) A, alpha = 63.67(2) degrees, beta = 71.24(2) degrees,
      gamma = 86.79(2) degrees, V = 1026(1) A3, Z = 2; 7.CH2Cl2, empirical formula
      C30H25Cl8N7O2Re2, crystal system triclinic, space group P1, a = 12.522(6) A, b =
      12.857(8) A, c = 13.182(7) A, alpha = 67.75(4) degrees, beta = 88.30(4) degrees,
      gamma = 82.09(4) degrees, V = 1945(2) A3, Z = 2.

PMID- 11229036
TI  - Magnetic properties of diruthenium(II,III) carboxylate compounds. Crystal
      structures of Ru2Cl(mu-O2CCH=CHCH=CHMe)4 and Ru2Cl(mu-O2CCH2OMe)4.
AB  - The reaction of Ru2Cl(mu-O2CMe)4 with 2,4-hexadienoic and 2-methoxyacetic acids
      affords the compounds Ru2Cl(mu-O2CR)4 [R = CH=CHCH=CHCH3 (1), CH2OMe (2)]. The
      structures of both complexes have been determined by X-ray crystallography. 1
      crystallizes in the triclinic space group P-1 with a = 9.264(1) A, b = 12.661(8)
      A, c = 12.839(5) A, alpha = 106.09(3) degrees, beta = 77.89(2) degrees, gamma =
      97.73(3) degrees, and Z = 2. 2 crystallizes in the nonstandard monoclinic space
      group P2(1)/c with a = 12.132(4) A, b = 11.570(2) A, c = 13.674(2) A, beta =
      91.18(2) degrees, and Z = 4. Complexes 1 and 2 show [Ru2(mu-O2CR)4]+ units linked
      by chloride ions, giving zigzag chains with Ru-Cl-Ru angles of 119.43(4) degrees
      and 110.11(7) degrees, respectively. The Ru-Ru bond distances are 2.2857(9) A (1)
      and 2.290(1) A (2). A magnetic study, in the 2-300 K temperature range, of the
      new compounds and the previously described Ru2Cl(mu-O2CR)4 [R = CHMe2 (3), CMe3
      (4), C4H4N (5)] is described. The polymeric complexes 1 and 2 and the
      nonpolymeric 3-5 show a large zero-field splitting which varies from 53.9 to 68.1
      cm-1. These complexes also show a weak, but not negligible, through-space
      intermolecular antiferromagnetic coupling not observed in the previous magnetic
      studies carried out on these types of compounds.

PMID- 11229037
TI  - One-pot synthesis and characterization of a chromophore--donor--acceptor
      assembly.
AB  - The acid-functionalized tris-heteroleptic chromophore--donor--acceptor assembly
      [RuII(bpyCOOH)(bpyCH2PTZ)(bpyCH2MV2+)](PF6)4]4+ (1) (bpyCOOH = 4'-methyl-2,2'
      bipyridine-4-carboxylic acid; bpyCH2PTZ = 10-((4'-methyl-2,2'-bipyridin-4
      yl)methyl)phenothiazine; bpyCH2MV2+ = 1-((4'-methyl-2,2'-bipyridin-4-yl)methyl)
      1'-methyl- 4,4'-bipyridinediium) was synthesized in a one-pot reaction by careful
      selection of the order of ligand addition to RuCl2(DMSO)4 (DMSO = dimethyl
      sulfoxide). The success of this method was based upon separation and isolation of
      1 from mixtures containing ligand-scrambled products by cation exchange
      chromatography. Metal-to-ligand charge-transfer (MLCT) excitation in acetonitrile
      at 464 nm was followed by intramolecular electron transfer to give a redox
      separated state [RuII(bpyCOOH)(bpyCH2PTZ.+)(bpyCH2MV.+)]4+ with an efficiency of
      eta RS = 0.35 +/- 0.05.

PMID- 11229038
TI  - Luminescent ruthenium(II) bipyridyl-phosphonic acid complexes: pH dependent
      photophysical behavior and quenching with divalent metal ions.
AB  - The synthesis, redox behavior, and photophysical properties of a series of Ru(II)
      bipyridyl complexes having diimine ligands with phosphonate and phosphonic acid
      substituents are presented. The phosphonate-containing ligands examined include
      diethyl 4-(2,2'-bipyrid-4-yl)benzylphosphonate (bpbzp), diethyl 4-(2,2'-bipyrid-4
      yl)-phenylphosphonate (bppp), and 4,4'-(diethyl phosphonato)-2,2'-bipyridine
      (bpdp), and the [(bpy)2Ru(L)](PF6)2 complexes of both the diethyl phosphonate and
      the phosphonic acid were prepared. The Ru(III/II) potentials are more positive
      for the phosphonate complexes than for the phosphonic acids, and the first
      reduction is localized on the phosphonate-containing ligand for the bppp and bpdp
      complexes. The first reduction of the phosphonic acid complexes is at more
      negative potentials and cannot be distinguished from bpy reduction. For the bppp
      and bpdp complexes luminescence arises from a Ru(d pi)-->bpy-phosphonate (pi*)
      MLCT state; the phosphonic acid complexes luminescence at higher energies from a
      MLCT state not clearly isolated on one ligand. Iron(III) and copper(II) complex
      with and very efficiently quench the luminescence of all the phosphonic acid
      complexes in nonaqueous solvents. The quenching mechanism is discussed on the
      basis of luminescence decay and picosecond transient absorption measurements.

PMID- 11229039
TI  - Oligomerization and oxide formation in bismuth aryl alkoxides: synthesis and
      characterization of Bi4(mu 4-O)(mu-OC6F5)6(mu 3-OBi(mu-OC6F5)3)2(C6H5CH3), Bi8(mu
      4-O)2(mu 3-O)2(mu-OC6F5)16, Bi6(mu 3-O)4(mu 3-OC6F5)(mu 3-OBi(OC6F5)4)3, NaBi4(mu
      3-O)2(OC6F5)9(THF)2, and Na2Bi4(mu 3-O)2(OC6F5)10(THF)2.
AB  - Exposing [Bi(OR)3(toluene)]2 (1, R = OC6F5) to different solvents leads to the
      formation of larger polymetallic bismuth oxo alkoxides via ether
      elimination/oligomerization reactions. Three different compounds were obtained
      depending upon the conditions: Bi4(mu 4-O)(mu-OR)6(mu 3-OBi(mu-OR)3)2(C6H5CH3)
      (2), Bi8(mu 4-O)2(mu 3-O)2(mu 2-OR)16 (3), Bi6(mu 3-O)4(mu 3-OR)(mu 3-OBi(OR)4)3
      (4). Compounds 2 and 3 can also be synthesized via an alcoholysis reaction
      between BiPh3 and ROH in refluxing dichloromethane or chloroform. Related oxo
      complexes NaBi4(mu 3-O)2(OR)9(THF)2 (5) and Na2Bi4(mu 3-O)2(OR)10(THF)2 (6) were
      obtained from BiCl3 and NaOR in THF. The synthesis of 1 and Bi(OC6Cl5)3 via salt
      elimination was successful when performed in toluene as solvent. For compounds 2
      6 the single-crystal X-ray structures were determined. Variable-temperature NMR
      spectra are reported for 2, 3, and 5.

PMID- 11229040
TI  - La48Br81Os8: isolated clusters in an unusual superstructure with significantly
      greater intercluster bonding.
AB  - Exploration of reactions in the La-Br-Z system for Z = Fe, Ru, and Os in welded
      Nb containers at 900-950 degrees C resulted in only the title phase. The
      La48Br81Os8 stoichiometry is very close to that of known triclinic Pr6Br10Os but
      with an approximately 32-times larger cell, 138 independent atoms, and completely
      different intercluster connectivities in a complex monoclinic superstructure (a =
      33.076(5) A, b = 23.466(3) A, c = 23.537(2) A, beta = 110.701(4) degrees, P2(1)/c
      (No. 14), Z = 4, 23 degrees C). Tetragonally compressed, approximately 16 e-
      lanthanum octahedra centered by Os are heavily interbridged by Br, including Br(f
      a) (f = face) and Br(i-a-a) functions, to increase coordination numbers about
      some Br (to 4) and La (to 6) and to give an average of 19.63 bonded Br/La6Os vs
      the usual 18. These result in a cell volume 10% less than for an equivalent
      (hypothetical) La6Br10Os and Br-Br contacts as short as 3.30 A. Increased polar
      La-Br interactions presumably drive these changes. Optimal atom sizes for this
      structure have been found so far only in this novel compound.

PMID- 11229041
TI  - Miniature pigs.
AB  - Miniature pigs have become popular pets in North America, and veterinarians of a
      variety of clinical specialties may be called on for their care. Successful
      collection of blood from these animals requires familiarity with the location of
      sites for venipuncture and knowledge of adequate methods of restraint. In this
      article, restraint and techniques for venipuncture are described, as well as
      techniques for cerebrospinal fluid collection, semen collection, and vaginal
      cytologic examination. Interpretation of hematologic, serum biochemical, and
      urinalysis data are also discussed. Methods for diagnosis of skin diseases,
      gastrointestinal parasitism, and enteric infectious diseases are included in
      order to provide the practitioner with the essential knowledge and skills for a
      variety of clinical pathologic studies of this unique pet.

PMID- 11229042
TI  - Clinical pathology of the domestic rabbit. Acquisition and interpretation of
      samples.
AB  - Diagnostic laboratories are receiving increasing numbers of samples from
      practitioners as they strive to diagnose complex disease processes and manage
      rabbit cases. Proper acquisition of diagnostic samples and interpretation of
      results are key skills necessary for successful management of medical cases. This
      article reviews the collection and interpretation of clinicopathologic samples
      commonly used in rabbits.

PMID- 11229043
TI  - Ferrets. Clinical pathology and sample collection.
AB  - Diagnostic sampling and interpretation in the ferret are similar to other small
      mammals in many ways. There are several aspects of clinical pathology and
      diagnostic procedures, however, that are unique to the ferret. This article is
      designed to assist the clinician in obtaining and interpreting diagnostic samples
      for the ferret. Methods for blood and urine collection, bone marrow and organ
      aspirations, and organ biopsy techniques are discussed.

PMID- 11229044
TI  - Clinical pathology and sample collection in the laboratory rodent.
AB  - Common laboratory rodents have always been a favorite choice as a pet. Although
      diagnostic clinical pathology has not been viewed as practical for the rodent
      patient, current advances in technology make processing of small samples
      possible. Cultivation of the technical skills necessary for rodent sample
      collection has the potential to improve the standard of rodent veterinary care.
      This article provides an overview of rodent sample collection techniques,
      hematology, clinical biochemistry, serology, and clinical pathology of other
      tissues and fluids for laboratory rodents. General principles of clinical
      pathology can be applied across species. This article emphasizes the subtleties
      of the different rodent species which may impact diagnostic interpretation.

PMID- 11229045
TI  - Clinical pathology and sample collection of exotic small mammals.
AB  - The clinical pathology of some of the less common and newly emerging small mammal
      species is detailed in this article. The species covered here include the
      chinchilla, prairie dog, African hedgehog, and sugar glider. Venipuncture sites
      and sampling techniques are discussed in general and for each species. Detailed
      information on the hematology and serum biochemistry values of these animals is
      presented in numerous tables. Specific information is also provided for
      urinalysis, fecal analysis, dermatologic sampling, and cytology.

PMID- 11229046
TI  - Collecting diagnostic samples in avian patients.
AB  - With the increasing owner demand of thorough medical evaluation of avian
      patients, clinicians are being required to collect meaningful diagnostic samples
      from bird species. The art of diagnosis stems from taking a complete medical
      history, performing a thorough physical examination, collecting appropriate
      diagnostics, and interpreting the collective information. This article focuses on
      methods of collecting diagnostic samples in avian patients.

PMID- 11229047
TI  - The diagnostic utility of serum protein electrophoresis.
AB  - Routine serum protein electrophoresis is recognized as the most reliable
      assessment of avian protein profiles in health and disease and has replaced
      biochemical determination of albumin and A:G ratio in the ability to predict
      abnormalities of clinical significance. The importance of considerable species
      differences to the overall interpretation of avian electrophoresis is well
      established and constitutes a continued challenge to the avian specialist and to
      the providing laboratories to continue the pursuit of species-specific, even age-
      and gender-specific, reference ranges. Patterns for various diseases continue to
      emerge as more scrutiny is applied to the use of this tool in avian diagnostics
      for overall health assessment as an adjunct to specific disease diagnosis and for
      both prognostic and therapeutic monitoring.

PMID- 11229049
TI  - Raptor hematology and chemistry evaluation.
AB  - Hematologic and biochemical evaluation of raptor blood samples is discussed to
      guide the practitioner in the diagnosis of disease. Species and age variation in
      the raptors in response to the laboratory values is also addressed.

PMID- 11229048
TI  - Avian clinical pathology.
AB  - Much of the information previously available concerning avian clinical pathology
      was drawn from data from domestic avian species, in particular, poultry. Clinical
      pathology of nondomestic avian species such as psittacines, however, has come a
      long way toward establishing normal reference values for caged birds. As a
      result, it is important for the avian clinician to learn which clinical tests can
      be used to detect and evaluate a single disease or disease processes by learning
      what information is gained from hematologic, biochemical, or cytologic samples
      acquired during a patient's clinical examination.

PMID- 11229050
TI  - Observations of basic diagnostic profile patterns seen in some common disorders
      of backyard poultry species.
AB  - Poultry species--chickens, ducks, geese--are becoming increasingly popular as
      pets. As such, requests for accurate diagnoses and treatment are being received
      by the veterinary community from the public. Unlike the food animal and
      production-oriented aspects of poultry medicine, success with these pet birds is
      contingent on preserving the human-pet bird bond, as defined by the individual
      client. This article presents some of this author's observations in diagnostic
      profiles on some selected disorders of backyard poultry.

PMID- 11229051
TI  - Sample collection and clinical pathology of reptiles.
AB  - Clinical pathology techniques can guide the clinician to diagnose and treat the
      reptile patient successfully. Text, tables, pictures, and diagrams in this
      article describe blood and cytology collection techniques and interpretation for
      the common pet reptile species.

PMID- 11229052
TI  - Diagnostic sampling of amphibians.
AB  - This article discusses basic restraint, sample collection, and guidelines for
      interpretation. Common pathogens are mentioned throughout the article. Staff
      safety and involvement are emphasized. Clinicians are encouraged to record all
      results and contribute to this growing area of veterinary medicine.

PMID- 11229053
TI  - Hematology and clinical chemistry of cyprinid fish. Common carp and goldfish.
AB  - Evaluation of the clinical status in aquatic species is compromised by the
      limited diagnostic techniques that can be performed in these species. The
      hematologic and plasma chemistry parameters can provide predictive information,
      although these parameters can be highly variable owing to the influence of
      various intrinsic and extrinsic factors. However, these parameters are fairly
      stable in acclimated, well-managed fish if stress is reduced during collection
      and samples are properly collected and analyzed. Evaluation of any single
      parameter is not predictive and, therefore, not recommended. Ideally, the
      diagnostic protocol should include evaluation of the hematologic indices, total
      and differential cell counts, TPP, glucose, sodium, and chloride. The
      practitioner who is routinely involved in aquatic animal medicine should consider
      in-house evaluation of these parameters.

PMID- 11229054
TI  - Sample taking in invertebrate veterinary medicine.
AB  - Invertebrates are important as pets of the 1990s but more so from economic, pest,
      and conservation perspectives. Since diagnosis by clinical examination is often
      taxing in these species, sample taking provides valuable insight into disease
      processes. Infection and parasitic diseases can be diagnosed by techniques from
      simple microscopy through to polymerase chain reaction technology. Cytology,
      hematology, and clinical chemistry, although not widely practiced, can provide
      critical baseline data in a disease investigation.

PMID- 11229055
TI  - Vascular brachytherapy approval for clinical use.

PMID- 11229056
TI  - Yttrium-90 delivered via a centering catheter and afterloader, given both before
      and after stent implantation, inhibits neointima formation in porcine coronary
      arteries.
AB  - BACKGROUND: Intracoronary radiation (IR) studies have shown reduction of
      neointima formation (NF). Extrapolation of animal studies with beta-radiation to
      clinical trials have shown variable results, which may be related to dosimetry,
      centering issues, and/or shielding of beta-rays by the stent metal. We examined
      the effect of yttrium-90 (90Y), a pure beta-emitter delivered via an automatic
      afterloader to a centering catheter, on the inhibition of NF in balloon-injured
      (BI) porcine coronary arteries as well as in arteries receiving 90Y either prior
      to or following stent implantation (SI). METHODS: Twenty-three swine (44 coronary
      arteries) were studied. In the first study, IR (18 Gy at 1.2 mm from the balloon
      surface) was administered in 17 arteries following BI, while eight control
      arteries were subjected to BI only. In the second study, 10 swine (19 coronary
      arteries) underwent SI. IR (18 Gy) was administered in six arteries before and in
      eight arteries after SI, while five control arteries received SI only. The
      animals were sacrificed 2 weeks after BI and 4 weeks after SI. Their coronaries
      were perfusion fixed and stained, and vessel parameters (intimal area [IA] and
      medial fracture length [FL]) were analyzed by computer-aided histomorphometry.
      RESULTS: Arteries subjected to IR following BI had less NF compared to controls
      (IA/FL = 0.14 +/- 0.2 mm vs. 0.49 +/- 0.2 mm; P = 0.003). IA was reduced
      significantly in the arteries receiving radiation before and after SI compared to
      controls (0.92 +/- 0.98 and 0.00 +/- 0/00 vs. 2.72 +/- 1.2 mm2; P = 0.014),
      despite similar SI in all groups. CONCLUSIONS: IR with 90Y delivered via a
      centering catheter is safe and effective with complete and homogenous inhibition
      of NF in the context of BI or SI in the porcine coronary model.

PMID- 11229057
TI  - Effect of stent on radiation dosimetry in an in-stent restenosis model.
AB  - PURPOSE: Intravascular brachytherapy is the leading modality being evaluated for
      treatment of in-stent restenosis. Stent struts may have an effect on the dose
      distributions of various radiation sources. We evaluated dosimetry in a stented
      coronary artery model using a variety of beta and gamma sources and stent
      materials. METHODS: We determined the dose distributions with and without stent
      in the in-stent restenosis model. Three beta-particle emitting radionuclides, 90Y
      (2.3 MeV), 144Pr (3.0 MeV), and 106Rh (3.5 MeV), and two gamma-ray emitters,
      192Ir (380 keV) and 125I (30 keV), were studied. Stent materials included
      stainless steel, nitinol, and tantalum. Monte Carlo dose calculations were
      performed in a stent model of multiple stent struts placed at 1.5 mm from the
      source. Isodose curves were generated and the ratios of dose rates with and
      without stent, the stent factors, were evaluated. A stent factor of greater or
      less than unity represents dose enhancement or reduction in the presence of a
      stent. RESULTS: For the three beta radionuclides, dose reduction was found on the
      adventitial side of the stent strut and dose enhancement was noted on the luminal
      side. On the luminal side, the maximum dose enhancement ranges from 7% to 29%,
      and the dose reduction on the adventitial side ranges from 13% to 43%. Both the
      reduction and enhancement effects were most pronounced for the high atomic number
      material, tantalum. For a given stent material, the dose reduction and
      enhancement are similar for the three beta radionuclides. For the gamma sources,
      the stent had no effect for the high-energy 192Ir, but for the low-energy 125I,
      drastic dose reduction on the adventitial side was observed (up to 86% for
      tantalum stent), and about 10% dose enhancement on the luminal side was also
      noted. The dose reduction with 125I was more pronounced than that seen with the
      beta sources. CONCLUSIONS: The presence of stent struts significantly affects
      dose distributions of 90Y, 106Rh, 144Pr, and 125I. The maximum dose reduction can
      be as much as 86%. 192Ir was unaffected. These factors need to be considered in
      choosing radionuclides and dose prescriptions in treating in-stent restenosis.

PMID- 11229058
TI  - Calculation of dose distribution near an innovative concentric balloon catheter
      for endovascular brachytherapy.
AB  - PURPOSE: Using a radioactive solution-filled catheter for intravascular
      irradiation has the potential problem of chemical and radiological toxicity in
      the case of a balloon rupture. In order to reduce this risk, an innovative
      concentric balloon catheter was developed. METHODS AND MATERIALS: The concentric
      balloon was made by inner and outer balloons filled with saline and radioactive
      solution, respectively. The optimal inner radius was determined by comparing the
      dose rate reduction vs. the volume reduction for various inner and outer radii
      for 188Re, 32P, and 90Y solutions. RESULTS: For a balloon with an outer radius of
      1.5 mm, there was no advantage of a concentric balloon. For balloons with outer
      radii of 3.0 and 5 mm, the optimal inner radius was 1.5 and 3 mm, respectively.
      CONCLUSIONS: With the newly designed concentric balloon, the risk of toxicity can
      be reduced while keeping the dose rate high enough so that the treatment times
      within tolerable limits are still maintained.

PMID- 11229059
TI  - Endovascular brachytherapy of transjugular intrahepatic portosystemic shunt.
AB  - PURPOSE: To evaluate the technical feasibility and efficacy of endovascular
      brachytherapy with Iridium-192 in the prevention of restenosis caused by
      neointimal hyperplasia of transjugular intrahepatic portosystemic shunt (TIPS).
      MATERIALS AND METHODS: The endovascular brachytherapy with high dose rate
      automatic afterloading system was performed in six patients with recurrent of
      stenosis of TIPS. We used a single dose fraction of 12 Gy delivered at 3
      millimeter (mm) from the source axis to the stenotic vessel segment in five
      patients with spiral Z-stent, and 15 Gy at 5 mm in one patient with Wallstent.
      RESULTS: Follow-up time ranged from 148 to 639 days. In one patient, restenosis
      occurred in the treated vessel segment, diagnosed 71 days after endovascular
      brachytherapy by doppler ultrasound. All other patients were, during the follow
      up time, without restenosis in the irradiated vessel segment. Radiation
      associated side effects were not observed. CONCLUSIONS: Endovascular
      brachytherapy of TIPS is technically feasible and may be done as a part of the
      percutaneous revision of the shunt. This pilot study may be the largest
      experience of treating TIPS restenosis in humans to date. For definitive
      conclusions, a lot of studies are needed.

PMID- 11229060
TI  - Dosimetric penumbra effects in catheter-based intravascular brachytherapy using a
      centered photon or beta line source.
AB  - PURPOSE: In catheter-based intravascular brachytherapy, either photon or beta
      emitters are often used in a linear arrangement so that blood vessels of 10-30 mm
      lengths can be treated. With a line source, the dose gradient in the radial
      direction and longitudinal direction depend on the type of radionuclides used in
      the treatment. The purpose of this study was to investigate the dose fall-off at
      the edges of a linear source in a blood vessel for different types of photon and
      beta emitters. MATERIALS/METHODS: Dose distributions were calculated on
      cylindrical blood vessels of various radii. Radioactive sources of 192Ir, 125I,
      103Pd, 188Re, 32P, and 90Y/Sr were studied. All the sources were assumed to be in
      the form of a line. The dose rate at a point in space produced by a radioactive
      source was computed by integrating the point dose rate kernel of the
      corresponding radionuclide over the radioactive line. The point dose rate kernel
      was computed with Monte Carlo simulation of radiation transport. The edge effects
      were characterized with three newly defined quantities: longitudinal dose
      uniformity (LDU), effective coverage length (ECL), and margin length (ML). LDU
      was defined as the ratio of dose at a distance along the long axis of the vessel
      to the dose at center. ECL was defined as the length over which the LDU was
      greater than 0.95. ML was defined as half of the length difference between source
      length L and ECL, which is essentially the length segment at each edge that is
      covered by the source physical length but is being underdosed. RESULTS: All beta
      emitters provided more uniform dose distributions and covered a larger portion of
      blood vessels longitudinally than photon emitters. Typical MLs were 2-3 mm for
      beta emitters and 4-6 mm for gamma emitters. As the radial depth of the point of
      interest increased, both the LDU and ECL decreased and ML increased. The ML
      increased from 2 to 3 mm for beta emitters and from 4 to 6 mm for photon emitters
      when the radial depth of the point of interest increased from 1.5 to 2.5 mm
      (typical proximal and distal media points for a 3-mm diameter lumen). The ML
      increased with increasing source length for all radionuclides. For beta emitters
      the ML increased initially from 1.5 mm to more than 2.5 mm as source length
      increased from 5 to 10 mm. When the source length was longer than 15 mm, the ML
      remains nearly constant, about 3 mm. For photon emitters, ML increased
      continuously from 1.5 mm to more than 6.0 mm, as source length increased from 5
      to 50 mm. CONCLUSIONS: A formalism to quantify the dose uniformity along the
      length of a blood vessel undergoing catheter-based intravascular brachytherapy
      has been developed. This formalism was used to study the edge effects at the ends
      of several beta and photon sources. The results indicated that for a centered
      source the ML at each end due to penumbra effects was about 2 to 3 mm for beta
      emitters; about 4-6 mm for photon emitters. The ML increases as the radial depth
      of point of interest in the vessel increases. The ML increases also with
      increasing source length, especially for photon sources.

PMID- 11229061
TI  - On the need for massive additional shielding of a catheterization laboratory for
      the implementation of high dose rate 192Ir intravascular brachytherapy.
AB  - PURPOSE: There is a widespread belief in the cardiology and radiation oncology
      community that high dose rate 192Ir intravascular brachytherapy cannot be
      implemented without massive additional shielding of the conventional
      catheterization labs. The purpose of this work is to show that this is a myth,
      which is not based on sound radiation protection principles. METHODS: Exposure
      rates in air were calculated for a variety of point and line sources of 192Ir.
      Exposures per treatment at different distances from the source were calculated
      for a typical intravascular brachytherapy treatment of a 15-Gy dose at a radial
      distance of 2 mm from the source and for source lengths in the range of 0 to 10
      cm. Additionally, exposure rates outside the catheterization lab were calculated
      for various lead shielding thicknesses typical of conventional X-ray facilities.
      These rates were used along with the NCRP recommendations on radiation facility
      design to assess shielding requirements. RESULTS: For a treatment dose of 15 Gy
      at 2 mm, the occupational exposure per treatment at 2 m in air without any tissue
      attenuation or shielding was 7.8 mR for a lesion length of 3.0 cm. This
      exposure/treatment is independent of the dose rate or the activity of the source.
      However, it increases as lesion length is increased, increasing from 5.4 to 24.9
      mR as lesion length increased from 2 to 10 cm. Exposures in unrestricted areas
      outside the catheterization lab using the NCRP shielding rationale can be kept
      below 2 mR per treatment and using appropriate workload, use, and occupancy
      factors below 2 mR per week. CONCLUSIONS: The feasibility of implementing a high
      dose rate 192Ir intravascular brachytherapy program in a catheterization
      laboratory is totally independent of the dose rate or the activity of the source.
      If it is feasible to implement 192Ir brachytherapy in a conventional
      catheterization lab using low activity 192Ir seeds, then it is also feasible to
      do so with a high activity 192Ir afterloader.

PMID- 11229062
TI  - Endovascular brachytherapy in coronary arteries: the Rotterdam experience.
AB  - PURPOSE: The use of endovascular coronary brachytherapy to prevent restenosis
      following percutaneous transluminal coronary angioplasty (PTCA) began in April
      1997 at the Department of Interventional Cardiology of the Thoraxcenter at the
      University Hospital of Rotterdam. This article reviews the more than 250 patients
      that have been treated so far. METHODS AND MATERIALS: The Beta-Cath System
      (Novoste), a manual, hydraulic afterloader with 12 90Sr seeds, was used in the
      Beta Energy Restenosis Trial (BERT-1.5, n = 31), for compassionate use (n = 25),
      in the Beta-Cath System trial (n = 27) and in the Beta Radiation in Europe (BRIE,
      n = 14). Since the Beta-Cath System has been commercialized in Europe, 57
      patients have been treated and registered in RENO (Registry Novoste). In the
      Proliferation Reduction with Vascular Energy Trial (PREVENT), 37 patients were
      randomized using the Guidant-Nucletron remote control afterloader with a 32P
      source wire and a centering catheter. Radioactive 32P coated stents have been
      implanted in 102 patients. In the Isostent Restenosis Intervention Study 1 (IRIS
      1), 26 patients received a stent with an activity of 0.75-1.5 microCi, and in the
      IRIS 2 (European 32P dose response trial), 40 patients were treated with an
      activity of 6-12 microCi. In two consecutive pilot trials, radioactive stents
      with non-radioactive ends (cold-end stents) and with ends containing higher
      levels of activity (hot-end stents) were implanted in 21 and 17 patients,
      respectively. RESULTS: In the BERT-1.5 trial, the radiation dose, prescribed at 2
      mm from the source train (non-centered), was 12 Gy (10 patients), 14 Gy (10
      patients) and 16 Gy (11 patients). At 6-month follow-up, 8 out of 28 (29%)
      patients developed restenosis. The target lesion revascularization rate (TLR) was
      7 out of 30 (23%) at 6 months and 8 out of 30 (27%) at 1 year. Two patients
      presented with late thrombosis in the first year. For compassionate use patients,
      a restenosis rate (RR) of 53% was observed. In the PREVENT trial, 34 of 37
      patients underwent an angiographic 6-month follow-up. The doses prescribed at 0.5
      mm depth into the vessel wall were 0 Gy (8), 28 Gy (9), 35 Gy (11) and 42 Gy (8).
      TLR was 14% in the irradiated patients and 25% in the placebo group. One patient
      developed late thrombosis. In the IRIS 1 trial, 23 patients showed an RR of 17%
      (in-stent). In the IRIS 2 trial, in-stent restenosis was not seen in 36 patients
      at 6-month follow-up. However, a high RR (44%) was observed at the stent edges.
      CONCLUSIONS: The integration of vascular brachytherapy in the catheterization
      laboratory is feasible and the different treatment techniques that are used are
      safe. Problems, such as edge restenosis and late thrombotic occlusion, have been
      identified as limiting factors of this technique. Solutions have been suggested
      and will be tested in future trials.

PMID- 11229063
TI  - Leakage of a liquid 188Re-filled balloon system during intracoronary
      brachytherapy. A case report.
AB  - We are reporting the first case of an accidental radioactive 188Re leakage of a
      liquid-filled balloon system. Different analytical methods estimated that
      approximately 4 mCi 188Re were released. The radiation burden was reduced
      considerably by the combined therapy with perchlorate and forced volume diuresis.
      Estimated exposures to all organs were very low with 1.8 rad. A total body
      nuclear scintigraphy demonstrated uniform 188Re distribution, without specific
      organ concentration.

PMID- 11229065
TI  - [How to better convert scientific information into practice].

PMID- 11229064
TI  - [The largest medical fair at Dusseldorf: nurses gaining knowledge at the MEDICA
      fair].

PMID- 11229066
TI  - [Future of the aged in society].

PMID- 11229067
TI  - [Advanced nursing education in intensive care and anesthesiology: the link
      between high technology and human nature].

PMID- 11229068
TI  - [Care of patients in the operating room: report of experience of nursing students
      after the final examination].

PMID- 11229069
TI  - [The experience in intensive care nursing].

PMID- 11229070
TI  - [Blood saving and the role of nurses during anesthesia].

PMID- 11229072
TI  - [Key qualification in anesthesia and intensive care nursing].

PMID- 11229071
TI  - [Toxic epidermal necrolysis: the skin peels off in every case].

PMID- 11229073
TI  - [Making the patient a participant in care].

PMID- 11229074
TI  - [Protection of motherhood: laws should not interfere with the rights of pregnant
      women].

PMID- 11229075
TI  - [How demanding is the job of the nurse?].

PMID- 11229076
TI  - [Experience in Gambia: the goal is helping to self-help].

PMID- 11229077
TI  - [Nursing services need more personnel].

PMID- 11229078
TI  - Pharmacists diagnose drugs demand.

PMID- 11229079
TI  - Private insurers cover the options.

PMID- 11229080
TI  - [Two new studies on health risks connected to cellphones. But we still know too
      little].

PMID- 11229081
TI  - ["Menopause medicine" a growing discipline. Many questions on hormones and
      women's health are still unanswered].

PMID- 11229083
TI  - [Vulvovestibulitis: a "new" diagnosis confusing for the gynecologist.
      Multifactorial condition with a psychosomatic component].

PMID- 11229082
TI  - [Hormone therapy in climacteric. Different effects of estrogen and gestagen on
      the risk of breast and endometrial cancer].
AB  - Use of hormone replacement therapy alleviates menopausal symptoms effectively,
      prevents osteoporosis and may even reduce the risk of cardiovascular disease and
      dementia. However, little is known about the risk of breast cancer and
      endometrial cancer after long-term use of different estrogen-progestin
      combinations. A large epidemiological study in Sweden, in which combined estrogen
      progestin treatment was predominantly used, is reported.

PMID- 11229084
TI  - [Craniofacial surgery in Sweden in 2000].

PMID- 11229085
TI  - [Statistic decline--more complicated in reality].

PMID- 11229086
TI  - [Poisson's regression better than x2-test. Suicide frequency in Gotland as a
      basis for analysis of changes of rare events in a small group].

PMID- 11229087
TI  - [A case report. Hypotensive reaction caused by albumin infusion].
AB  - Hypotensive reactions during surgical procedures cause diagnostic problems in
      establishing whether the hypotension is due to blood loss or pharmaceuticals or
      other causes. A case of hypotension probably due to an albumin infusion is
      described. Bradykinin effects are probably the cause of many hypotensive
      reactions. Angiotensin-converting enzyme (ACE) inhibitors reduce degradation of
      bradykinin and thus increase the risk of hypotensive reactions. When possible,
      doctors should consider withholding ACE inhibitors 24 hours before surgical
      procedures likely to require albumin transfusions.

PMID- 11229088
TI  - [High alcohol concentration in blood in rats resulted in massive apoptosis].

PMID- 11229089
TI  - [Clever prevention results in fewer suicides].

PMID- 11229090
TI  - [Part-time work and individual scheduling was the solution of personnel problems
      in Ljungby].

PMID- 11229091
TI  - [Johan Christian Stark--a physician in the society of good poets].

PMID- 11229092
TI  - [The dissertation--a test which should fulfill certain minimum requirements].

PMID- 11229093
TI  - [Reply 1: The doctoral dissertation: Karolinska Institute has checkpoints to help
      or to stop doctoral candidates].

PMID- 11229094
TI  - [Reply 2: The doctoral dissertation: technicalities from a glass house].

PMID- 11229095
TI  - [An action plan--for the benefit of all!].

PMID- 11229096
TI  - [An action plan to make entire health care function].

PMID- 11229097
TI  - [Reply: We belong together--as thick as thieves].

PMID- 11229098
TI  - [Circumcision--Sweden as (questionable) international model].

PMID- 11229100
TI  - [The Aphasia Society--patient society as a link in the rehabilitation process].

PMID- 11229099
TI  - [Hypothermia was the most probable cause of death of men in the Andree
      expedition].

PMID- 11229101
TI  - [Did Fredrika Bremer suffer of DAMP?].

PMID- 11229102
TI  - A great deal of progress has been made during the past 30 years in developing
      drugs to treat hypertension.

PMID- 11229103
TI  - The effect of alpha-blockers on cardiac function.

PMID- 11229104
TI  - Metabolic effects of alpha-blockers.

PMID- 11229105
TI  - Combination of alpha-blockers with other antihypertensive drugs.

PMID- 11229106
TI  - Effect of prazosin GITS, atenolol, nifedipine SR, and enalapril on ADP-induced
      platelet aggregation.
AB  - A randomized, observer-blind, parallel-group study was carried out to compare the
      effect of prazosin GITS, atenolol, nifedipine SR, and enalapril on platelet
      aggregation, measured at a time expected to coincide with trough plasma levels of
      these drugs. 24 patients (age-30 to 60 yrs) with uncomplicated mild to moderate
      hypertension who completed a placebo run-in phase successfully were recruited in
      this study. They were randomly allocated to one of the 4 treatments: prazosin
      GITS 2.5 mg OD (Group 1), atenolol 50 mg OD (Group II), nifedipine SR 20 mg BD
      (Group III), and enalapril 5 mg OD (Group IV). All the drugs were given for 7
      days, and blood samples were collected at 0 hr on day 1 (pre-treatment) and day 8
      (post-treatment). Based on the dose (incremental concentrations of ADP)--response
      (% maximum aggregation) curve obtained, 2.5 microM/L of ADP was used to compare %
      inhibition of platelet aggregation among the 4 groups. We found that prazosin
      GITS inhibited % maximum aggregation significantly (p = 0.02) at 2.5 microM/L of
      ADP. Such inhibitory effect was not seen in any of the other groups. The
      inhibition produced by prazosin GITS differed significantly from the action of
      the other 3 drugs (p < 0.05). This antiplatelet effect of prazosin GITS bears
      more clinical relevance in view of the fact that it was seen at a time which is
      expected to coincide with the trough plasma levels of prazosin.

PMID- 11229107
TI  - Alpha-blockers in hypertension: growing recognition as first line therapy.

PMID- 11229108
TI  - Insulin resistance and left ventricular mass in hypertensives.

PMID- 11229109
TI  - A study of the influence of insulin resistance on left ventricular mass in
      hypertensive patients.
AB  - OBJECTIVES: To study the influence of insulin resistance on the left ventricular
      mass in hypertensive subjects. MATERIAL AND METHODS: Thirty patients having
      uncomplicated essential hypertension were included in the study. Post-oral
      glucose load serum insulin level (2 hrs) was determined and this was used as a
      marker for insulin resistance. Two D-echocardiography was performed and left
      ventricular mass and left ventricular mass index were calculated. RESULT: Out of
      the 30 patients 18 were males and 12 were females. Eight were obese while the
      remaining 22 were non-obese. The patients were 27 to 70 years old. The mean age,
      height and weight were 54.83 +/- 9.46 years, 159.07 +/- 8.81 cm and 58.38 +/-
      11.03 kg, respectively. The post oral glucose load serum insulin levels in the
      study ranged from 57.65 to 210.81 microU/ml. The left ventricular mass and left
      ventricular mass index ranged from 42.58 to 310.8 g (mean 196.60 +/- 65.13 g) and
      42.74 to 185.59 g/m2 (mean 118.71 +/- 37.75 g/m2), respectively. The correlation
      coefficient ('r' value) between post oral glucose load serum insulin levels and
      left ventricular mass and left ventricular mass index were calculated.
      CONCLUSION: A strong positive correlation was observed between the post oral
      glucose load serum insulin levels and left ventricular mass ('r' = +0.750). A
      strong positive correlation between post oral glucose load serum insulin levels
      and left ventricular mass index ('r' = +0.757) was also observed. These
      correlations were found to be statistically highly significant (p < 0.01). This
      association was demonstrated independently of age, anthropometric measurements,
      systolic and diastolic blood pressure levels. Thus, in patients with essential
      hypertension, hyperinsulinemia (insulin resistance) has a role in promoting left
      ventricular hypertrophy.

PMID- 11229110
TI  - Drug utilisation pattern in sexually transmitted diseases and its economic
      considerations--a prospective study.
AB  - OBJECTIVES: WHO regularly revises guidelines for the treatment of these. There
      are very few studies reported on the drug utilization pattern of STD's in India.
      METHODS: In the present study, 325 patients attending the STD clinic of Lok Nayak
      Hospital were analysed over a period of six months. RESULTS: The demographic
      pattern of the patients was similar to those of studies reported earlier.
      Syphilis was the commonest of the STD's encountered; followed by viral STD's (c.
      acuminata and herpes progenitalis); gonorrhoea; chancroid and genital
      candidiasis. Out of a total of 409 drugs prescribed, the average number of drugs
      per prescription was 1.25. Sixty seven percent of the drugs were available in
      essential drug list of the hospital and 60% were prescribed in generic name.
      Ninety seven percent of the prescriptions were in accordance with WHO treatment
      guidelines. The cost of the drug treatment was comparable for c.acuminata,
      syphilis and chancroid while it was less for herpes progenitalis (HPG) due to
      acyclovir not being prescribed. However, it was more for gonorrhoea and
      candidiasis because of additional drugs. CONCLUSIONS: The present study shows a
      trend towards rational prescribing. It would be interesting to compare the
      results with a non teaching hospital.

PMID- 11229111
TI  - Prevalence of human immunodeficiency virus infection in and around Varanasi,
      Uttar Pradesh, India.
AB  - Human Immunodeficiency Virus (HIV) infection is rising rapidly in the eastern
      Uttar Pradesh; however no data is available regarding its positivity rate. We
      have screened 1239 cases of various groups. HIV seropositivity rate of 0.28% was
      noted. These results suggest that HIV infection is spreading rapidly in this part
      of the country. M. tuberculosis was the commonest co-infection amongst them
      (29.5%). We recommend routine HIV screening of all patients of tuberculosis,
      especially if the persons frequent the cities, visit foreign countries where sex
      tourism is encouraged or stay away from their spouses for long periods as true
      history of sexual contact with commercial sex workers was difficult to obtain
      from them.

PMID- 11229112
TI  - Suggested predictive indices for high altitude pulmonary oedema.
AB  - A study was conducted to evaluate the responses of chemoreceptors and pulmonary
      vascular bed to hypoxia, on two groups of soldiers exposed to similar altitudes,
      one group which did not suffer from high altitude (HA) maladies (Gp A) and the
      other when exposed to similar altitudes suffered from HA maladies (Gp B high
      altitude pulmonary edema--susceptible group (HAPE-S). Aim of this study was to
      find out whether these two tests could be used as a screening test for soldiers
      and sojourners proceeding to HA. Chemoreceptor responses were evaluated by
      hypoxic ventilatory response (HVR) test and the pulmonary vascular responses were
      studied by recording pulmonary artery pressure (PAP) changes under simulated
      hypoxia by breathing hypoxic gas mixtures (HGM) in both the groups. It was
      observed that HAPE-S subjects showed a reduced HVR response and an increase in
      PAP (systolic, diastolic, and mean). While Gp A subjects showed an increase in
      ventilation of 11.39 +/- 3.36 L, the same in Gp B subjects was 3.51 +/- 2.65 L.
      Thus, the comparison of increase in ventilation following HVR test between the
      two groups was highly significant. Under hypoxic gas mixture (HGM) breathing,
      systolic pressure of 28.2 +/- 6.9 and 52.6 +/- 11.0 mm Hg; diastolic pressure of
      11.4 +/- 3.8 and 23.6 +/- 5.8 mm Hg and mean pressure of 17.6 +/- 4.3 and 35.0 +/
      7.4 mm Hg were recorded in pulmonary arteries in Gp A and Gp B subjects,
      respectively. Gp B subjects showed a highly significant increase in all the three
      pulmonary pressures under HGM breathing.

PMID- 11229113
TI  - Brainstem auditory evoked potentials and somatosensory evoked potentials in
      cerebral malaria--a prognostic significance.
AB  - OBJECTIVE: To study the changes in brainstem auditory evoked potentials (BAEPs)
      and somatosensory evoked potentials (SSEPs) in cerebral malaria and to see their
      prognostic significance. METHODS: BAEPs and right median nerve SSEPs were
      performed in 25 adult patients of strictly defined cerebral malaria in acute
      stage in a semi-dark, sound proof chamber on four channel computerized multi
      basis OTE-Biomedica machine in department of neurology, SP Medical College,
      Bikaner. RESULTS: The abnormalities of BAEPs were delayed peak latency of wave
      III in 13/25 (52%) and wave V in 20/25 (80%) patients and delayed interpeak
      latencies (IPLs) of wave I-III in 9/25 (36%), wave I-V in 15/25 (60%) and wave
      III-V in 12/25 (48%) patients. In SSEPs delayed N20 was seen in 11/25 (44%);
      delayed IPLs of N13-N20 (central conduction time; CCT) in 12/25 (48%) patients.
      Distorted N20 was recorded in 12/25 (48%) patients. Both N13-N20 IPLs in SSEPs
      and wave III-V IPLs in BAEPs were delayed in five patients and all of them
      expired. Delayed N13-N20 with normal III-V IPLs was present in seven patients and
      two of them died, whereas delayed III-V IPLs with normal N13-N20 was present in
      seven patients, and one of them expired. In remaining six patients both the
      parameters were normal and one of them died. CONCLUSIONS: The values of BAEPs and
      SSEPs were abnormal in patients of cerebral malaria and it was observed that
      BAEPs/SSEPs alone was not useful for predicting the outcome of coma, whereas
      abnormalities in both was predictive of worst prognosis. The changes in evoked
      potentials (BAEPs and SSEPs) could be due to either interruption of conduction in
      central pathways because of structural changes due to petechial hemorrhages and
      malarial granuloma at multiple levels in the brain including brainstem or due to
      metabolic abnormalities.

PMID- 11229114
TI  - The cardiovascular and hemodynamic effects of erythropoietin in chronic renal
      failure.
AB  - OBJECTIVE: Left ventricular hypertrophy (LVH) has been identified as an
      independent risk factor for mortality in patients with chronic renal failure
      (CRF) and anemia has been proposed to contribute to LVH. The cardiovascular and
      hemodynamic effects of correction of anemia with recombinant human erythropoietin
      (rHU EPO) was assessed in a 12 week prospective study in patients with CRF.
      METHODS: Biochemical parameters and echocardiography were studied at the start
      and after three months therapy with EPO in 24 patients with CRF--11 predialysis
      (Group I) and 13 dialysis (Group II). RESULTS: The mean haemoglobin (Hb)--g/dl
      increased significantly from 7.5 +/- 1.0 to 10.1 +/- 1.1 in group I and from 6.7
      +/- 0.6 to 9.4 +/- 0.8 in group II (p < 0.05) on EPO therapy. The left
      ventricular mass index (LVMi)--g/m2 reduced significantly from 185.6 +/- 44.6 to
      158.3 +/- 4.1 in group I and from 158.0 +/- 26.9 to 131.6 +/- 22.1 in group II (p
      < 0.05 in both). The interventricular septal thickness (IVST) also showed a
      significant decline in both groups, 1.17 +/- 0.06 to 1.14 +/- 0.05 (group I) and
      1.09 +/- 0.25 to 1.01 +/- 0.21 (group II), p < 0.05 in both. The thickness of the
      left ventricular posterior wall remained unchanged. The left ventricular end
      diastolic and systolic diameters (LVEDD and LVESD) significantly reduced from
      their baseline values in both the groups (p < 0.05). The diastolic filling
      parameters across the mitral valve remained unchanged in both the groups. The
      cardiac index (CI)--L/min/m2 decreased from 3.53 +/- 0.3 to 3.03 +/- 0.27 in
      group I and from 3.31 +/- 0.64 to 2.80 +/- 0.60 in group II (p < 0.05) and the
      total peripheral resistance (TPR)--dynes/cm5/sec increased from 1567 +/- 164.8 to
      1883 +/- 190.7 in group I and from 1618 +/- 375.7 to 2004 +/- 437.3 in group II.
      The differences in all the parameters at the start and after 3 months of EPO were
      comparable in groups I and II. The mean arterial pressure (MAP) changed
      insignificantly in both the groups. CONCLUSIONS: To conclude, this study has
      shown that the decrease in LVMi with EPO reflects the role of anemia in the
      genesis of LVH and that the correction of anemia with EPO in CRF results in
      regression of LVMi and has a favourable effect on cardiovascular hemodynamics.

PMID- 11229115
TI  - Pharmaco-economic analysis of psychotropic drugs.
AB  - OBJECTIVES: To analyse cost and adverse reactions of psychotropic drugs for their
      cost-effective use. METHODS: Four hundred and sixty nine psychotropic
      formulations from CIMS, June 1998 were evaluated for (a) extent of variation in
      retail price for same strength and dosage form, (b) role of number of companies
      manufacturing the same formulation and (c) companies pricing their product at
      price less than average of maximum and minimum price in relation to number of
      products marketed by them. The side effects of antipsychotic and antidepressant
      drugs were graded for their severity and cumulative side effects score. Side
      effect index and cost index were calculated on relative basis and their product
      was used as cost benefit index. RESULTS: Fifty per cent of psychotropic drugs had
      less than 100% price variation with highest of 2049% for risperidone 4 mg
      tablets. A direct relationship existed between the drug cost and price variation
      wherever the variation crossed 200%. Similar trend was noticed between the
      minimum price variations and the number of companies marketing the product. There
      was no appreciable relationship between number of products marketed and pricing
      by the manufacturer. Cumulative side effect score was lowest (10) for
      trifluoperazine and pimozide and highest (15) for risperidone amongst
      antipsychotic drugs, whereas amongst antidepressants fluoxetine had lowest (1.75)
      and amitryptyline had highest (28.5) cumulative side effect score. CONCLUSION:
      One has to be more careful while selecting a brand of a drug when price variation
      is more (200-2049%). Trifluoperazine (1.0) and fluoxetine (1.7) were found to be
      most economical with better cost benefit index compared to thioridazine (494.2)
      and clomipramine (113.0) in their respective groups. Thus our analysis provides
      basic information regarding cost effective therapy with psychotropic drugs.

PMID- 11229117
TI  - Hyponatremia revisited.

PMID- 11229116
TI  - Nonalcoholic steatohepatitis: clinicopathological profile.
AB  - AIMS: To evaluate clinicopathological spectrum of nonalcoholic steatohepatitis
      (NASH) METHODOLOGY: Total 210 patients with chronic liver disease were evaluated.
      Detailed history has taken with clinical examination, laboratory investigations,
      radiological findings and liver biopsy whenever possible. RESULTS: From 210
      patients of chronic liver disease, 13 (6.19%) were diagnosed to have NASH (M:F =
      9:4, age range 37-72 years, mean age 55.4 +/- 9 years). Of 13 patients, four were
      referred for asymptomatic enzyme elevation, nine had right hypochondriac pain.
      Risk factors were diabetes in four cases, obesity four, steroid treatment two and
      hyperlipidemia in three cases. Laboratory investigations showed abnormal liver
      enzymes in all the cases. Ultrasonography and CT scan was helpful in predicting
      fatty liver. Liver biopsy showed steatosis with inflammation in all, fibrosis in
      two and cirrhosis in one patient. CONCLUSION: NASH is an important form of
      chronic liver disease, and is characterised by hepatomegaly, elevated liver
      enzymes. It is essential to diagnose this condition due to its progression to
      liver fibrosis and cirrhosis in some patients.

PMID- 11229118
TI  - Presidential address. Association of Physicians of India.

PMID- 11229119
TI  - Pictorial CME. Pseudoaneurysm of the common femoral artery.

PMID- 11229120
TI  - Endosulfan poisoning--a clinical profile.
AB  - OBJECTIVES: The objective of the study is to identify the clinical profile of
      endosulfan poisoning and also to recognise any biochemical parameters which
      indicate clinical or subclinical dysfunction of organs so that the offending
      agent can be easily identified in a given case of poisoning and appropriate
      treatment instituted promptly. METHODS: Forty four individuals who consumed food
      which was accidentally contaminated by endosulfan in a rural area were the
      subjects of the present study. Except the one who died, rest 43 were examined by
      the authors. A details history, regarding the item of food taken and quantity
      consumed was noted. Routine bio-chemical parameters like CBC, blood urea, serum
      creatinine, serum electrolytes, LFT, S Calcium, S Phosporus, were estimated, in
      fourteen of the patients who were admitted into this hospital. In seven of the
      patients who were available for follow up, laboratory parameters which were
      abnormal initially were repeated. RESULTS: Examination revealed that vital signs
      were stable. There was no jaundice, central nervous system examination showed
      varying grades of altered sensorium, normal sized pupils briskly reacting to
      light, normal oculocephalic reflex. There were no lateralising signs like
      hemiparesis. Plantars were bilateral extensor. There were no signs of meningeal
      irritation. Complete blood counts, blood sugar, urea, serum creatinine, serum
      electrolytes were all normal. Liver function tests in the form of SGPT, SGOT were
      abnormal. Serum bilirubin levels were normal. The values of SGOT and SGPT
      returned to normal at the end of six weeks. All patients were treated
      symptomatically. A postmortem examination carried out on the individual who died
      due to status epilepticus confirmed that the death was due to asphyxia.
      CONCLUSIONS: Endosulfan poisoning can be suspected by the primary CNS
      manifestations with or without clinical or laboratory evidence of other organ
      dysfunction like liver, kidney and muscle.

PMID- 11229121
TI  - Percussion of Traube's space--a useful index of splenic enlargement.
AB  - OBJECTIVE: To evaluate the sensitivity and specificity of palpation and
      percussion for splenic enlargement, as the accuracy of many of the clinical
      maneuvers we perform remains largely unstudied. METHODS: One hundred cases were
      selected at random from medical wards, and splenic enlargement was assessed by
      palpation and percussion of the Traube's space (Barkuns method), which was
      confirmed by the ultrasonography of the abdomen. The results of the various tests
      were tabulated and assessed statistically. RESULTS: 1) Performance of Traube's
      space percussion shows 24 true positive and 48 true negative cases, the test thus
      had an overall sensitivity of 67% and specificity of 75%. It was also found that
      the BMI of the false negative cases was significantly higher (29.43 Kg/m2). 2)
      Palpation as a diagnostic maneuver had a high specificity of 96.87% along with
      high false negative rate with overall low sensitivity of 44.44%. 3) Interpolation
      of findings of Traube's space percussion and palpation showed that maximum
      clinical utility could be achieved when both percussion and palpation were
      positive. CONCLUSION: Percussion of the Traube's space is a useful clinical
      screening test for splenomegaly, with a sensitivity of 67% and specificity of
      75%, as compared to palpation (sensitivity of 44.44% and specificity of 96.87%).
      And maximum clinical utility is achieved when both percussion and palpation are
      combined.

PMID- 11229122
TI  - Newer therapeutic concept in antiplatelet aggregation inhibition--GPIIb-IIIa
      receptor antagonists.
AB  - Numerous investigators have shown that the glycoprotein IIb/IIIa integrin
      mediates the final common pathway in platelet aggregation which has led to
      development of GP IIb/IIIa receptor antagonists. This article reviews the current
      status of GP IIb/IIIa receptor blockade in the management of coronary artery
      disease, examining the results of pivotal clinical trials.

PMID- 11229123
TI  - What is safe blood?

PMID- 11229124
TI  - The role of cough and hyperventilation in perpetuating airway inflammation in
      asthma.
AB  - Air flowing through a pipe exerts frictional stress on the walls of the pipe.
      Frictional stress of more than 40 N/m2 (velocity equivalent of air 113 m/s) is
      known to cause acute endothelial damage in blood vessels. The frictional stress
      in airways during coughing may be much greater, however, since the velocity of
      air may be as high as speed of sound in air. We suggest that high levels of
      frictional stress perpetuate airway inflammation in airways which are already
      inflamed and vulnerable to frictional stress-induced trauma in patients with
      asthma. Activities associated with rapid ventilation and higher frictional stress
      (e.g. exercise, hyperventilation, coughing, sneezing and laughing) cause asthma
      to worsen whilst activities that reduce frictional stress (Yoga 'Pranayama',
      breathing a helium-oxygen mixture and nasal continuous positive airway pressure)
      are beneficial. Therefore control of cough may have anti-inflammatory benefits in
      patients with asthma.

PMID- 11229125
TI  - Langerhans cell histiocytosis.
AB  - Langerhans cell histiocytosis (LCH) is a rare disorder affecting predominantly
      children and manifesting as bone pains, bony swellings and lytic lesions.
      Involvement of vertebrae as presenting manifestation is unusual. Here we have
      presented three cases of LCH, two of multifocal eosinophilic granuloma (MEG) and
      one of Hand Schuller Christian disease (HSC). One of the patients with MEG; had
      vertebral involvement as the presenting manifestation.

PMID- 11229126
TI  - Familial myelodysplastic syndromes.

PMID- 11229127
TI  - Renal cell carcinoma as significant manifestation of tuberous sclerosis complex.
AB  - We present a case of renal cell carcinoma diagnosed in 1982; aged 20 years.
      Regular follow up of the abdomen by USG noted first the presence of 2 nodules in
      the remaining kidney in 1994, age 30 and more lesions in 1997, aged 35. These
      were suspected to be angiomyolipomas on USG. The radiologist on this basis raised
      the question of tuberous sclerosis. Subsequent evaluation by
      internist/neurologist showed few adenoma sebaceum lesions a single ash leaf
      macule, a shagreen patch on the back, and characteristic multiple subependymal
      calcifications diagnostic of tuberous sclerosis on CT scan brain. The mentation
      was normal, there was history of only a single fit in childhood. The renal cell
      carcinoma was thus the first significant manifestation of tuberous sclerosis
      complex (TSC).

PMID- 11229128
TI  - An unusual systemic presentation of gout.
AB  - An elderly female presented with a systemic febrile illness and acute
      polyarthritis as the first manifestation of gout. She improved dramatically with
      anti-inflammatory therapy.

PMID- 11229129
TI  - McLeod syndrome (a variant of neuroacanthocytosis).

PMID- 11229130
TI  - A case of mitral valve prolapse presenting with various conduction system
      abnormalities.

PMID- 11229131
TI  - Acute life-threatening asthma with dramatic reversibility.

PMID- 11229132
TI  - Renal artery stenosis presenting as left ventricular dysfunction--complete
      recovery after renal angioplasty.

PMID- 11229133
TI  - Role of nebulized ipratropium bromide in acute exacerbation of early chronic
      obstructive airway disease.

PMID- 11229134
TI  - Hematological changes in visceral leishmaniasis.

PMID- 11229135
TI  - Association of retroperitoneal fibrosis with ankylosing spondylitis.

PMID- 11229136
TI  - Intramuscular anti-D globulin injection for treatment of chronic idiopathic
      thrombocytopenic purpura.

PMID- 11229137
TI  - Resurgence of malaria in Mumbai--is escalating chloroquine resistance a cause?

PMID- 11229138
TI  - Isonex prophylaxis in cases of SLE on immunosuppressive therapy.

PMID- 11229139
TI  - Ayurved (ancient Indian system of medicine) and modern molecular medicine.

PMID- 11229140
TI  - Sleep apnea syndrome is common in Indians with untreated primary hypothyroidism.

PMID- 11229141
TI  - Recurrent painless thyroiditis requiring total thyroidectomy.

PMID- 11229142
TI  - Hepatic involvement in tuberculosis.

PMID- 11229143
TI  - Prognostic role of stress thallium test in patients with significant coronary
      artery disease.
AB  - OBJECTIVE: The benign outcome of patients with a normal exercise thallium-201
      myocardial perfusion study has been well established. The aim of the study was to
      examine the prognostic implications of normal exercise tomographic thallium
      images in medically treated patients with angiographic evidence of coronary
      artery disease (CAD). METHODS: There were 68 patients in Group A with significant
      angiographic CAD (54 male and 14 female) aged 52 +/- 12 years, 42 had one, 18 had
      two and eight had three vessel CAD (50% diameter stenosis 1, Group B had 70
      patients who had normal coronary arteries at cardiac catheterization. RESULTS:
      Exercise test was submaximal in 40 (50.82%) patients, ST segment depression
      during exercise occurred in 28 patients (41.1%) and angina during exercise in 24
      patients (35.2%). Majority of patients (76.47%) were on anti-anginal therapy.
      During a mean follow up of 30 months only two patients had cardiac events in
      group A patient. One died of cardiac causes and one had non fatal myocardial
      infarction (event rate 0.96%/year). None of these 2 patients had positive ST
      response during exercise. In group B only one patient had non-fatal myocardial
      infarction. CONCLUSION: Medically treated CAD patients including those with
      multivessel CAD have a benign prognosis in the presence of normal exercise
      thallium images. These results have long term important implication in management
      of such patients and cost of health delivery.

PMID- 11229144
TI  - Dose and frequency of anti-snake venom injection in treatment of Echis carinatus
      (saw-scaled viper) bite.
AB  - OBJECTIVES: To assess the adequacy of initial standard dose of 100 ml of
      polyvalent anti-snake venom (ASV) and subsequent doses of 50 ml in correcting
      coagulation dysfunction in cases of viperine bite and to find the incidence of
      recurrence of coagulation dysfunction. The other objective was to correlate total
      requirement of ASV with initial coagulation profile. METHODS: Forty two adult
      patients of Echis carinatus bite with features of systemic envenomation, admitted
      over a period of 18 months, were monitored every six hours with bed-side clotting
      time (CT) and were given an initial standard dose of 100 ml of ASV intravenously.
      Further doses of 50 ml were administered six hourly until coagulation profile
      normalised or whenever a recurrence of coagulation dysfunction observed. RESULTS:
      Twenty one (50%) of 42 patients who received initial standard dose of 100 ml of
      ASV required a subsequent 50 ml of ASV. Ten (23.8%) of them required a further 50
      ml on subsequent test (making the total requirement at least 200 ml). Sixteen
      (72.7%) of 22 patients who had incoagulable blood at entry required further dose
      of anti-snake venom (after initial 100 ml), six required 150 ml and ten 200 ml or
      more before CT returned to normal. Recurrence of venom antigenemia as evidenced
      by prolonged clotting time was noticed in 15 patients (35.7%). The mean dose
      requirement of anti-snake venom was 179.2 ml. CONCLUSIONS: Total requirement of
      anti-snake venom correlated positively with degree of coagulation dysfunction at
      entry. Hence patients having incoagulable blood at entry should be administered
      higher initial dose of ASV i.e., 150-200 ml. If needed as judged by CT,
      subsequent dose of ASV in patients having still incoagulable blood should be 100
      ml (and those having mild dysfunction 50 ml) until total correction occurs
      Recurrence of coagulation dysfunction was observed in approximately one-third of
      patients and thus, CT should be monitored even after total correction.

PMID- 11229145
TI  - Clinical and ultrasonographic findings of carcinoma of gallbladder in Indian
      patients.
AB  - OBJECTIVE: To determine the clinical and ultrasound appearances of carcinoma
      gallbladder in Indian patients. METHODS: The study included all patients
      suspected to have gallbladder malignancy, attending the gastroenterology
      department from January 1989 to February 1997. These patients underwent
      ultrasonographic examination with a grey scale sector scanner (Aloka SSD-630)
      with a 3.5 MHz transducer after an overnight fast. Histological confirmation was
      done at surgery, by US guided fine needle aspiration cytology or by direct
      biopsy/aspiration of the palpable mass. RESULTS: There were a total of 92 cases
      of cytologically and histologically proven carcinoma of gallbladder. A distinct
      female preponderance was seen with a male:female ratio of 1:3.6. The mean +/- SD
      age was 47.9 +/- 19.6 years (range 25-75 years). The histological confirmation
      was done at surgery in 10% of patients, by US guided fine needle aspiration
      cytology in 50 cases (54%) or by direct biopsy/aspiration of the palpable mass in
      33 (36%) of cases. Pain in the right hypochondrium was the commonest presenting
      symptom (91%) followed by anorexia (88%) and weight loss (67%). Surgical
      obstructive jaundice was observed in 54% cases while 10.9% presented with biliary
      sepsis. A mass of mixed echogenicity protruding in the lumen of the gallbladder
      was seen in the majority of cases (52.8%). Less commonly infiltration of the
      gallbladder wall (33.7%) or a mass replacing the gallbladder (14.1%) was
      encountered. Gallstones were associated in 57% of patients with gallbladder
      malignancy. The elevated stone sign and peripancreatic nodal spread were
      important clues for gallbladder malignancy. CONCLUSION: A high index of suspicion
      of gallbladder malignancy in elderly Indian female patients presenting with
      features of choletithiasis, and awareness of the ultrasound findings may lead to
      early diagnosis and radical resection of this highly lethal malignancy.

PMID- 11229146
TI  - Elective stenting of extracranial carotid arteries.
AB  - OBJECTIVES: In symptomatic and asymptomatic patients with significant carotid
      artery stenosis, surgical endarterectomy has been shown to be beneficial when
      compared with medical management. Carotid stenting is evolving as an alternative
      technique for treating such patients. This prospective study was designed to
      assess the feasibility and safety of carotid angioplasty and stenting. METHODS:
      Fourteen patients (15 carotid arteries) with significant carotid artery stenosis
      were enrolled. These patients were in the age range 46 to 84 years (mean 60.9 +/-
      7 years) and there were 12 males (86%). All of these patients were symptomatic
      with either TIA (n = 8) or stroke (n = 6). Wallstents were used in all the cases
      to stent the carotid arteries. One patient underwent bilateral carotid artery
      stenting. RESULTS: Carotid angioplasty and stenting was successful in 13 out of
      14 (92.8%) patients and 14 out of 15 (93.3%) carotid arteries, with reduction in
      mean (+/- SD) stenosis from 86 +/- 6% to 3 +/- 3%. There was one episode of minor
      stroke, no major stroke or death during the initial hospitalization. Another
      patient had a minor stroke with patent ipsilateral carotid artery (on repeat
      angiography) during the first 30 days after the procedure. This patient was also
      found to have asymptomatic thrombus formation in the contralateral carotid stent
      which resolved with intravenous anticoagulation. During a mean follow up of 6 +/-
      2 months there has been no recurrence of symptoms. CONCLUSIONS: Based upon our
      limited experience we believe that percutaneous carotid angioplasty with stenting
      is feasible with low periprocedural complication rate.

PMID- 11229147
TI  - Serum vitamin E in chronic myeloid leukaemia.
AB  - OBJECTIVE: Experimental evidence suggests that free radicals can participate in
      tumour promotion and malignant conversion and free radical scavengers like
      alphatocopherol act as first line of defense against peroxidation of
      polyunsaturated fatty acids. The present study was planned to estimate serum
      vitamin E levels in patients of chronic myeloid leukaemia (CML). METHODS: Serum
      vitamin E levels were estimated in 25 CML patients before and after the
      treatment. Twenty five age and sex matched healthy individuals served as control.
      RESULTS: Mean serum vitamin E levels were significantly decreased in CML patients
      before starting the treatment as compared to control. Also, vitamin E levels
      increased significantly after the treatment, but, remained lower than the
      control. CONCLUSION: Vitamin E levels were lower in CML patients as compared to
      control and the levels increased significantly after treatment in these patients.
      This could be due to decrease in oxidative stress due to decrease in tumour load.

PMID- 11229148
TI  - Evaluation of cardiac function in iron deficiency anemia before and after total
      dose iron therapy.
AB  - OBJECTIVE: To evaluate the cardiac function before and after the total dose iron
      therapy (TDI) and to correlate the myocardial function to the rise in haemoglobin
      after TDI in patients of iron deficiency anemia. METHODS: The study included 30
      patients of iron deficiency anemia who presented to our institution in the last
      one year. There were 11 men and 19 women with the mean age of 30 years.
      Parameters compared before and after TDI infusion included clinical features,
      haemoglobin, electrocardiogram (ECG), treadmill stress test (TST) and 2
      dimensional echocardiogram (2D echo). RESULTS: During the study period 30
      patients (11 men and 19 women) were included for TDI. The mean haemoglobin level
      increased from 5 gm/dl to 5.7 gm/dl 4 days after TDI. The congestive cardiac
      failure disappeared in four out of eight patients after TDI. The mean heart rate
      on the ECG pretherapy was 102.66 +/- 14.9 and post therapy 93.4 +/- 14.9 (p =
      0.011). The TST results showed improvement in effort tolerance in 17 out of 24
      patients (p = 0.0012) and it improved much before there was a significant rise in
      haemoglobin. CONCLUSION: Impaired ventricular performance is observed in patients
      with iron deficiency anemia. After TDI the left ventricular function improved
      before there was a significant rise in haemoglobin level proving the theory that
      correction of the electrophysiological abnormalities of the heart in iron
      deficiency patient by TDI may be the result of correction of iron at the tissue
      level.

PMID- 11229149
TI  - Insulin secretory response in healthy adult offspring of hypertensive parents.
AB  - OBJECTIVES: The present study was done to observe the insulin secretory response
      in healthy adult offspring of normotensive and hypertensive parents as the
      etiology of essential hypertension is largely treated as unknown. METHODS: The
      insulin secretary response was observed in 20 healthy adult offspring of
      normotensive parents (Group I) and 25 healthy adult offspring of hypertensive
      parents (Group II). The mean serum insulin levels were assessed at fasting, 30,
      60, 90 and 120 minutes after 75 grams of oral glucose load in both groups.
      RESULTS: The mean serum insulin levels in fasting state was higher in group II
      (32.40 +/- 18.59) than group I (17.90 +/- 11.98) (p < 0.01). After 30 minutes
      mean serum insulin levels were higher in group II than group I (88.00 +/- 56.04,
      40.5 +/- 15.15 respectively, p < 0.001). There was no statistically significant
      difference after 60, 90 and 120 minutes of oral glucose load (p > 0.05).
      CONCLUSIONS: Our observations suggest that the insulin secretory response in
      fasting and 30 minutes after oral glucose load was earliest metabolic abnormality
      in subjects at high risk for developing hypertension i.e. offspring of
      hypertensive parents.

PMID- 11229150
TI  - Aortic valve disease and left dominant coronary system a significant association.
AB  - OBJECTIVES: To study the dominance of coronary artery distribution in patients
      with aortic valve disease. MATERIAL AND METHODS: The prevalence of left dominant
      coronary artery system in patients with aortic valve disease was compared with
      patients without aortic valve disease undergoing coronary angiography. Group 1
      consisted of 237 patients with symptomatic aortic valve disease and Group 2
      consisted of 241 consecutive patients without aortic valve disease undergoing
      cardiac catheterisation. RESULTS: Forty two patients in Group 1 and 20 patients
      in Group 2 (p < 0.01) showed a left dominant pattern of supply. Fifteen patients
      in Group 1 and eight patients in Group 2 showed a co-dominant pattern of supply
      (p = NS). Among patients in Group 1, there was no significant difference in the
      increased prevalence of left dominant system between patients with congenital or
      acquired aortic valve disease or between the different categories of aortic valve
      lesions. CONCLUSION: Patients with aortic valve disease show a statistically
      significant higher prevalence of left dominant pattern of blood supply. This
      higher prevalence of left dominance is seen in all categories of aortic valve
      lesions, namely, predominant aortic stenosis, predominant aortic regurgitation
      and in combined aortic stenotic and regurgitant lesions.

PMID- 11229151
TI  - Pregnancy in premature ovarian failure: a possible role of estrogen plus
      progesterone treatment.
AB  - Premature ovarian failure (POF) is a common occurrence in women during their
      reproductive years. There is paucity of data on spontaneous ovulation and
      subsequent pregnancies in such women. In this report, we describe three women
      with POF, two of whom had spontaneous conceptions and the third resumed
      spontaneous regular menstrual cycles. All these women had received oestrogen
      progesterone tablets for many cycles (ethyl oestradiol 0.05 mg and levonorgestrel
      0.25 mg a day, 21 days a month). We speculate about the possibility of elevated
      gonadotrophins causing down regulation of gonadotrophin receptors and restoration
      of the sensitivity of the few remaining ovarian follicles by lowering of serum
      gonadotrophins with oestrogen therapy.

PMID- 11229152
TI  - Current status of low molecular weight heparins in clinical practice.

PMID- 11229153
TI  - Pictorial CME.

PMID- 11229154
TI  - Botulinum toxin: from toxin to therapeutic agent.

PMID- 11229155
TI  - The healer inside a physician.

PMID- 11229156
TI  - 19-year female with cerebrovascular accident.

PMID- 11229157
TI  - Tuberculous liver abscess.
AB  - Tuberculosis (TB) of liver is rare but may have a variety of presenting features
      similar to other more common conditions. A case of tuberculosis liver abscess
      with right sided pleural effusion is reported.

PMID- 11229158
TI  - Tuberculous liver abscess.

PMID- 11229159
TI  - Hepatic artery mycotic aneurysm of tubercular aetiology.
AB  - Hepatic artery aneurysm caused by tuberculosis is extremely rare, the commonest
      being atherosclerosis and vasculitis. A 13 year boy admitted with suspected
      disseminated tuberculosis had a hepatic bruit. Patient died of aneurysmal rupture
      before antemortem etiological diagnosis could be established. Postmortem
      examination revealed widespread tubercular lesions in the chest and abdomen and
      hepatic artery aneurysm.

PMID- 11229160
TI  - Primary fourth ventricular hemorrhage.
AB  - A case of primary fourth ventricular hemorrhage with spontaneous recovery is
      reported. To the best of our knowledge, there is no previous report of this rare
      clinical entity.

PMID- 11229161
TI  - Pseudohypoparathyroidism.

PMID- 11229162
TI  - Spontaneous knotting of nasogastric tube.

PMID- 11229163
TI  - Priapism is rare in sickle cell disease in India.

PMID- 11229164
TI  - Anomalous origins of right coronary and left anterior descending coronary
      arteries: angiographic profiles.

PMID- 11229165
TI  - Near fatal asthma following ingestion of diclofenac sodium tablet.

PMID- 11229166
TI  - Wide QRS tachycardia.

PMID- 11229168
TI  - Retained intra-abdominal drain: a nine year journey.

PMID- 11229167
TI  - Metronidazole induced acute confusional agitated state.

PMID- 11229169
TI  - Intradialytic complications in bicarbonate haemodialysis.

PMID- 11229170
TI  - Preliminary study of aerosol delivered insulin by oral inhalation in NIDDM.

PMID- 11229171
TI  - Medical transcription: its future in India.

PMID- 11229172
TI  - Inflammation in atherosclerosis.

PMID- 11229173
TI  - Comparison of two schedules of hepatitis B vaccination in patients with mild,
      moderate and severe renal failure.

PMID- 11229174
TI  - Khatnil: a potentially lethal ayurvedic insecticide.

PMID- 11229175
TI  - Interlobar effusion.

PMID- 11229176
TI  - Interlobar effusion.

PMID- 11229177
TI  - Fixed drug eruption due to multi-vitamin multi-mineral preparation.

PMID- 11229178
TI  - The gastrointestinal tract in uremia.

PMID- 11229179
TI  - A study of gastric emptying in chronic renal failure.
AB  - In a prospective controlled study, 32 patient with chronic renal failure (CRF)
      and 11 healthy volunteers were evaluated for solid gastric emptying at our
      institute over a period of 2 years. The study sought to identify the incidence of
      abnormal gastric emptying in these patients, the factors influencing the
      development of abnormal gastric emptying and whether gastrointestinal symptoms
      correlated with abnormal gastric emptying. The efficacy of prokinetic drugs
      Cisapride and Erythromycin in improving delayed gastric emptying in these
      patients with CRF was also compared and evaluated. We observed delayed gastric
      emptying in 69% of our patients. About 50% of our patients with delayed gastric
      emptying had no gastrointestinal symptoms suggesting a poor correlation between
      the two. Delayed gastric emptying was observed frequently in patients with
      peripheral neuropathy and/or autonomic neuropathy. Gastric emptying in CRF
      appears to be independent of age, sex, duration of disease, BUN, creatinine and
      H. phylori infection. Oral Cisapride and Erythromcin are effective gastrokinetic
      agents in these patients. Identification of delayed gastric emptying in patients
      with CRF and treatment with these drugs may reduce gastrointestinal symptom
      related morbidity.

PMID- 11229180
TI  - Lipid peroxidation and vitamin E in ischemic heart disease.
AB  - The study was carried on 90 adult cases which were divided into 3 groups of 30
      cases each. Group A consisted of 30 normal healthy controls whereas Group B and C
      comprised of 30 patients each of chronic stable ischaemic heart disease and of
      acute myocardial infarction (AMI), respectively. Patients in all the 3 groups
      were age and sex matched. Group C consisted of 17 cases of anterior wall
      myocardial infarction, 10 of inferior wall, 2 of anterolateral and 1 of antero
      inferior MI and they had an average 6.96 +/- 3.39 hours of chest pain before
      hospitalization. Serum vitamin E in group A, B and C on day 1 was 7.90 +/- 3.23,
      5.345 +/- 2.37 and 1.302 +/- 1.090 micrograms/ml, respectively and
      malondialdehyde (MDA) levels in these groups were 0.759 +/- 0.27, 0.780 +/- 0.334
      and 3.092 +/- 1.124 nmol/ml, respectively. Vitamin E and MDA levels in group C on
      day 3 were 3.382 +/- 1.088 micrograms/ml and 1.492 +/- 0.849 nmol/ml,
      respectively. In Group C, vitamin E levels were significantly decreased (p <
      0.001) as compared to controls and remained low after 2 days. MDA levels were
      raised more than 3 times in AMI group (p < 0.01) and decreased slightly after 2
      days but were elevated compared to controls. Findings suggest that vitamin E
      deficiency is inversely related to lipid peroxidation and is elevated during AMI.
      Therefore supplementation of vitamin E in AMI would be beneficial.

PMID- 11229181
TI  - Lipid peroxide, beta-carotene and alpha-tocopherol in ischaemic stroke and effect
      of exogenous vitamin E supplementation on outcome.
AB  - 30 patients with CT proven infarct presenting within 24 hours of the acute event
      were included in the study with 20 age and sex matched controls. On day 1 and day
      15 of stroke, levels of plasma lipid peroxide (oxidant) and plasma alpha
      tocopherol and beta carotene (antioxidant) were estimated. The patients were
      randomly assigned to two groups, one group receiving 300 mg/day of vitamin E for
      15 days. Neurological examination was conducted according to Mathew scale on day
      1 and day 15 and rehabilitation assessment was done at day 15 and at 6 weeks
      according to Barthel Index. On day 1, the mean value of plasma lipid peroxidation
      in controls was 4.97 +/- 1.44 nmol/ml and in stroke patients 5.89 +/- 1.56
      nmol/ml (p < 0.05). The plasma beta-carotene in controls was 2.35 +/- 1.09 mg/L
      while in stroke patients was 1.07 +/- 0.55 mg/L (p < 0.001) and plasma alpha
      tocopherol in control 9.74 +/- 2.76 micrograms/ml as compared to 7.57 +/- 2.92
      micrograms/ml in stroke patients (p < 0.02). Initially the plasma lipid peroxide
      levels are high and antioxidant levels are low in patients of ischemic stroke.
      Exogenous vitamin E supplementation does not have any significant effect on early
      neurological outcome but it does bring about significant changes in subsequent
      recovery and rehabilitation of patients of stroke.

PMID- 11229182
TI  - Visual evoked responses in ethambutol induced optic neuritis.
AB  - Pattern evoked responses were recorded in 46 patients of tuberculosis on
      ethambutol and 16 healthy subjects. Deterioration in visual acuity was documented
      in two patients (4.3%). P100 latency was delayed in 16 cases (34.8%), while in 12
      patients (26.1%) both latency and amplitude were affected. A cut off latency
      value of > or = 140 ms was associated with ophthalmological findings. The
      incidence of subclinical toxicity as detected by visual evoked response (VER) was
      higher in older subjects, patients on higher doses of ethambutol (> or = 20
      mg/kg/day) and longer duration of treatment. Of two cases with objective ocular
      signs, one who reported for follow up after two months had recovered completely
      after stopping ethambutol. Recording of VER is an extremely useful objective test
      for subclinical optic nerve damage.

PMID- 11229183
TI  - Early haemodialysis in acute tubular necrosis.
AB  - The study was conducted in 35 cases of acute tubular necrosis of varied
      aetiology. Cases were divided in 2 groups, Group A--17 cases treated
      conservatively and Group B--18 cases managed by early haemodialysis. Criteria for
      early haemodialysis were blood urea < 120 mg% and serum creatinine < 7 mg%.
      Before starting therapy both the groups had comparable biochemical and renal
      parameters (p > 0.05). Overall mortality was lower in Group B as compared to
      Group A (22.2% Vs 29.4). Complication events such as uraemic encephalopathy,
      pulmonary oedema, haematemesis and malena, thrombophlebitis and vomiting were
      significantly lower in Group B (p < 0.05). Hospital stay was also significantly
      lower (p < 0.05) in Group B (18 +/- 2.5 days Vs 28 +/- 3 days), this can reduce
      the cost of treatment also.

PMID- 11229184
TI  - Control of malaria: the rapid fever surveillance programme.
AB  - Eighty-five villages out of nearly 300 villages of Tiptur taluka covering a
      population of 47,271 where the incidence of Plasmodium falciparum (PF) malaria
      was very high, were selected for a programme during Aug 93 which lasted for 29
      months until the end of Dec 95. Ten days of fever radical treatment (FRT) and 54
      weekly and 29 fortnightly rapid fever surveillance (RFS) programmes were
      conducted. 64,142 blood smears were examined out of which 21,542 were positive
      for malaria and 14,291 were of PF type. There were 9858 PF cases during the last
      5 months of 1993, which came down to 349 by the end of 1995. Fever morbidity
      which was nearly 1000 new cases per day during FRT came down to 120, 78, and 30
      new cases per day during 1993, 1994 and 1995, respectively. Parasite index (PI)
      for PF Malaria was 140-321 during 1993, came down to 0.6-15 at the end of the
      study. Four rounds of DDT, two rounds of Ikon and one round of Delta-methrin were
      sprayed in four and two PHC areas, respectively during this period. Asymptomatic
      carriers for PF malaria were detected in the children under 14 years of age
      (3.1%). This programme did prove very effective in bringing down morbidity and
      mortality due to PF Malaria in the community.

PMID- 11229185
TI  - Cerebral venous thrombosis in pregnancy and puerperium--a prospective study.
AB  - During a prospective study of cerebrovascular accidents we evaluated 64 cases of
      cerebral venous thrombosis (CVT) in pregnancy and puerperium. CVT made up
      approximately half of the young strokes and 40% of strokes occurring in females.
      Majority of them were below 25 years of age, multipara women from rural areas who
      were delivered at home by untrained dais. While 79.6% cases occurred during first
      two weeks after delivery, the incidence of antepartum CVT was also higher at
      7.8%. Majority of the patients had meningoencephalitic (70.32%) presentation.
      Others in the spectrum had either acute fulminant type (18.7%), neuropsychiatric
      (6.25%) or pseudotumour cerebri like presentation (4.68%). Patients with
      neuropsychiatric and pseudotumour cerebri like presentation had a better
      prognosis while those with acute fulminant type had a poorer outcome. The
      patients with bilateral hemorrhagic infarcts and diffuse cerebral edema on CT
      scan had a poorer prognosis. A lower mortality rate (18.75%) could be achieved
      with early diagnosis and quick institution of planned therapy.

PMID- 11229186
TI  - Evaluation of oral dipyridamole electrocardiography test in ischaemic heart
      disease.
AB  - Forty-three cases of ischaemic heart disease of the age group 35-72 yrs with
      positive treadmill test (TMT) results were administered dipyridamole in the
      morning on empty stomach. Heart rate, BP and ECG were recorded before and every
      15 mins after oral dipyridamole upto 2 hrs. ECG was repeated every 5 mins when
      patients developed angina or ischaemic ECG changes. Oral dipyridamole
      electrocardiography test (ODET) was found to be positive in 21 (48.83%) cases and
      majority of them developed ST depression in 25-40 mins and persisted for less
      than 30 mins. While compared with TMT results patients having chest pain, lower
      target heart rate (< 75%), shorter time to onset (< 2 mins) of ST depression and
      longer duration (> 8 mins) of ST depression had significantly higher rates of
      positivity on ODET than those without these manifestations. There were minor
      changes in hemodynamic parameter (heart rate, systolic and diastolic blood
      pressure) and other minor side effects encountered include mild headache and
      benign unifocal VPCs. Oral dipyridamole is viewed as a safe drug and may be used
      as a substitute for TMT specially in economically poor and physically disabled
      patients with significant coronary artery disease.

PMID- 11229187
TI  - Epidemiological studies and treatment of hypertension.

PMID- 11229188
TI  - Pictorial CME. beta Thalassemia intermedia.

PMID- 11229189
TI  - Clinical profile of wolf bite cases in Jalgaon district.

PMID- 11229191
TI  - Bat-transmitted rabies: the global scene.

PMID- 11229190
TI  - Endothelins and anti-endothelins.
AB  - Endothelins, endothelin-1 (ET1), endothelin-2 (ET2) and endothelin-3 (ET3), are
      the most potent vasoconstrictor peptides released by endothelial cells. ET
      production is stimulated by vasopressor hormones, platelet-derived factors,
      coagulation products and cytokines, whereas nitric oxide and prostacyclin reduce
      ET production. ET bind to ETA and ETB receptors and produce marked and sustained
      rise in blood pressure, intense vasoconstriction of coronary arteries and have
      positive inotropic and chronotropic effects on myocardium. Besides, they
      influence neuroendocrine, renal and smooth muscle functions. ET appears to
      function mostly as a paracrine or an autocrine hormone. ET may have a role in
      hypertension, atherosclerosis, heart failure, coronary artery disease, renal
      insufficiency, vascular hypertrophy, respiratory and cerebrovascular conditions.
      Several antagonists of ET acting at receptor level or influencing endothelin
      converting enzyme (ECE) are under investigation and have great potential as
      agents for use in the treatment of wide spectrum of disease entities and as
      biologic probes for understanding the actions of ET in human beings.

PMID- 11229192
TI  - Drug induced diabetes mellitus.
AB  - Drug induced diabetes occurs due to a variety of drugs and mechanisms.
      Considering the vast number of diabetics in this country and also the wide
      variety of drugs prescribed for diabetic as well as non-diabetic patients
      especially the elderly, the entity of drug induced diabetes does not appear to be
      very common. This suggests that an underlying and often unsuspected abnormality
      probably increases the risk of developing diabetes mellitus. Sulphonylureas which
      act primarily by enhancing insulin secretion, would not be an effective
      therapeutic modality for countering drug induced diabetes. In case the drug has
      to be continued, insulin therapy is the most efficacious approach. The new
      thiazolidinedione drugs such as troglitazone which increase insulin sensitivity
      in patients with glucose intolerance and diabetes, may be very useful in cases
      where insulin resistance has resulted in diabetes.

PMID- 11229193
TI  - Investigation of proteinuria--how and how much?

PMID- 11229194
TI  - Development of diabetes mellitus and hypertension due to aggravation of insulin
      resistance after estrogen--progestogen in HAIR-AN syndrome.

PMID- 11229195
TI  - Yellow phosphorous poisoning--smoking stool syndrome.

PMID- 11229196
TI  - Prolonged pyrexia in a diabetic due to systemic aspergillosis.
AB  - Immuno-compromised patients are susceptible to a variety of opportunistic
      infections. Systemic aspergillosis is one such common infection in neutropenic
      subjects. A case of primary cutaneous aspergillosis with fungimia in a diabetic
      is reported.

PMID- 11229197
TI  - Senior-Loken syndrome.

PMID- 11229198
TI  - Thoracic renal ectopia.

PMID- 11229199
TI  - Viral hepatitis B with pleural complication.

PMID- 11229200
TI  - Self induced seizures with heliotaxis.

PMID- 11229201
TI  - A case of cor triatriatum.

PMID- 11229202
TI  - Massive metallic mercury ingestion without toxicity.

PMID- 11229203
TI  - Tuberculous pancreatitis.

PMID- 11229204
TI  - Neurological manifestations of falciparum malaria.

PMID- 11229205
TI  - Halofantrine in G-6 PD deficiency.

PMID- 11229206
TI  - Clinical dysautonomia in diabetes mellitus.

PMID- 11229207
TI  - Helicobacter pylori--current status.

PMID- 11229208
TI  - Comprehensive management of stroke--"the concept of stroke units".

PMID- 11229209
TI  - Diagnostic criteria of fever of unexplained origin needs further modification.

PMID- 11229211
TI  - Green coconut water.

PMID- 11229210
TI  - Complications with low dose methotrexate in rheumatoid arthritis.

PMID- 11229212
TI  - Nontraumatic coma.

PMID- 11229213
TI  - Hypoglycaemia in falciparum malaria.

PMID- 11229214
TI  - Importance of blood glucose level at the time of admission in severe and
      complicated malaria.
AB  - A prospective study of blood glucose level at the time of admission was done on
      532 cases of severe and complicated malaria admitted in classified malaria ward
      at PBM Hospital, Bikaner. Eleven patients had blood glucose level < 40 mg% (< 2.2
      mmol/L) and all were unconscious with diagnosis of cerebral malaria. Four
      patients became conscious with i.v. infusion of 25% dextrose only without
      receiving any specific antimalarial treatment. Recognition of these patients of
      "falciparum malaria with hypoglycaemia" by blood glucose estimation at the time
      of admission can significantly affect the ultimate outcome. The mortality trend
      was more in patients having blood glucose level < 40 mg% (< 2.2 mmol/L) in
      comparison to group of patients having blood glucose level between 41 to 60 mg%
      (2.2 to 3.3 mmol/L) and was least in those having blood glucose level > 60 mg% (>
      3.3 mmol/L).

PMID- 11229216
TI  - Post lumbar puncture headache: is bed rest essential?
AB  - Headache following lumbar puncture is a well known and well described
      complication. Various manoeuvres have been tried to prevent post lumbar puncture
      headache--the commonest being bed rest for 4 to 24 hours following lumbar
      puncture, though its value is questionable. Randomised controlled clinical trial
      was done to evaluate the effect of 24 hours bed rest on the incidence and
      severity of post lumbar puncture headaches. Two hundred and eight patients were
      randomly allocated to either the ambulant or the bed rest group. Patients were
      interviewed by a single investigator on days 0, 1, 2 and 7 about the presence and
      nature of headache. Other relevant clinical and laboratory data pertaining to the
      lumbar puncture was collected. The overall incidence of post lumbar puncture
      headache was 17%; 15% in the ambulant and 18% in the bed rest group. Of the
      patients who had headaches, severe headache was observed in 57% in the ambulant
      and 12% in the bed rest group (p = 0.02). Other variables did not alter the
      outcome of headaches. Bed rest does not appear to alter the incidence of post
      lumbar puncture headaches, but reduces the severity in those who get headaches,
      after a lumbar puncture.

PMID- 11229215
TI  - Mitoxantrone, mitomycin-C, methotrexate combination chemotherapy with
      radiotherapy and/or surgery in stage III (T4B, NO-2, M0) breast cancer.
AB  - Results of primary surgery with or without locoregional radiotherapy (LRRT) are
      poor in stage III (T4b, NO-2, M0) breast cancer. Combination of mitoxantrone,
      mitomycin-c and methotrexate (MMM) has been reported to be as efficacious as
      doxorubicin based protocols with advantages of reduced nausea, vomiting, alopecia
      and cardiotoxicity. We tested MMM chemotherapy with LRRT and surgery in locally
      advanced breast cancer (LABC) with a view to assess response, survival, breast
      conservation, cost and toxicity. Fifty two previously untreated patients were
      given Mitoxantrone: 8 mg/m sq by infusion on days 1 and 21, Mitomycin-C: 8 mg/m
      sq by infusion on day 1 and Methotrexate: 35 mg/m sq i.v. on days 1 and 21.
      Cycles were repeated every 42 days. After 3 cycles LRRT was given if lump reduced
      to less than 2 cms. Otherwise patients were subjected to modified radical
      mastectomy (MRM) or radical mastectomy (RM). Following this 3 more cycles of
      chemotherapy were given. Patients with soft tissue, skin or heavy nodal
      involvement also received LRRT. Tamoxifen 20 mg daily was prescribed at the end
      of chemotherapy to postmenopausal patients. Complete/partial responses were seen
      in 5 and 26 patients, respectively after chemotherapy giving an overall response
      of 59.5%. Twenty four patients each had LRRT and MRM/RM. Responses could be
      significantly enhanced by LRRT/and or surgery. Nineteen out of 25 relapses were
      at distant sites. Breast conservation was achieved in 24/52 (46%) patients. Three
      year disease free and overall survival was 54% and 65%, respectively. There was 1
      toxic death. Severe prolonged myelosuppresion was seen in those who also received
      LRRT. Mucositis, alopecia, nausea and vomiting were minor problems. Overall,
      combination was less expensive than doxorubicin based protocols.

PMID- 11229218
TI  - Usefulness of echocardiography in detection of subclinical carditis in acute
      rheumatic polyarthritis and rheumatic chorea.
AB  - Detailed echocardiographic analysis was performed in 10 children with first
      episode of acute rheumatic fever who presented with acute rheumatic polyarthritis
      or rheumatic chorea and had no clinically detectable evidence of active carditis.
      Significant changes were observed in the form of mitral valve prolapse with
      regurgitation in 3, aortic valve prolapse with regurgitation in 1 and mitral
      valve billowing without regurgitation in 1 patient each. A significant (p <
      0.001) anterior mitral chordal elongation was observed in both the groups-
      rheumatic polyarthritis and chorea when compared with age and sex matched control
      subjects. Mitral annular diameter was found to be increased (p < 0.001) in
      patients presenting with polyarthritis alone. These observations of clinically
      silent but echocardiographically detectable element of carditis forms the basis
      of how patients of acute rheumatic fever develop permanent valvular deformities
      in their latter lives without revealing any cardiac affection earlier.

PMID- 11229217
TI  - Clinical profile of myasthenia gravis.
AB  - Seventy three patients with myasthenia gravis were studied over 9 years period
      (1987-1995) in departments of neuromedicine, respiratory care unit,
      cardiothoracic unit of Institute of Postgraduate Medical Education and Research
      and Bangur Institute of Neurology, Calcutta, with reference to their clinical
      presentations, laboratory findings and various modes of treatment. Commonest age
      of presentation was 5th decade in men and 3rd decade in women. Fifty five percent
      of patients belong to type 2A myasthenia gravis (Osserman classification).
      Presentation was insidious (67.2%) and course was slowly progressive (65.7%) in
      majority of cases. Fatigability and ptosis were commonest clinical presentation
      and diurnal variation was noticed in 60% of cases. Edrophonium test was positive
      in 90.4% of cases and repetitive nerve stimulation showed 93.5% positivity in 30
      cases. 27 patients (36.9%) underwent thymectomy and out of these, 89% of patients
      showed hyperplastic change and thymoma in 11% of cases. Mortality rate including
      both operated and nonoperated patients was recorded to be 9.6%. We observed
      earlier onset of myasthenia in male, higher incidence of oculo-bulbar involvement
      and lower incidence of respiratory problem and thymoma.

PMID- 11229220
TI  - Pictorial CME. Guinea worm infection.

PMID- 11229219
TI  - Oral zinc therapy in diabetic neuropathy.
AB  - The present double blind randomized study was conducted on 50 subjects; 20 age
      and sex matched healthy controls (Group--I); 15 patients of diabetes mellitus
      with neuropathy who received placebo for 6 weeks (Group--IIA); and 15 patients of
      diabetes mellitus with neuropathy who were given supplemental zinc sulphate (660
      mg) for 6 weeks (Group--IIB). Serum zinc level, fasting blood sugar (FBS) and
      post prandial blood sugar (PPBS) levels and motor nerve conduction velocity
      (MNCV) were estimated on day 0 and after 6 weeks in all subjects. Serum zinc
      levels were significantly low (p < 0.001) in group IIA and IIB as compared to
      healthy controls (Group--I) at baseline. After 6 weeks the change in pre and post
      therapy values of FBS, PPBS and MNCV (median and common peroneal nerve) were
      highly significant (P = < 0.001) for group IIB alone with insignificant change (P
      = > 0.05) in group IIA. No improvement (P = > 0.05) in autonomic dysfunction was
      observed in either groups. Therefore, oral zinc supplementation helps in
      achieving better glycemic control and improvement in severity of peripheral
      neuropathy as assessed by MNCV.

PMID- 11229221
TI  - Idiopathic isolated global T wave inversion: a report of 10 patients.
AB  - Ten patients (9 females and 1 male) between the age of 40-60 years with atypical
      chest pain and isolated global T wave inversion (in the absence of QRS complex or
      ST segment abnormality) and normal coronary arteries are described. The cause of
      these changes remains unknown.

PMID- 11229222
TI  - Adverse drug reactions to fluoroquinolones at a tertiary care hospital in
      northern India.
AB  - Use of fluoroquinolones has increased considerably in the last 5-6 years in our
      hospitals. With a view to ascertain their safety and the type of adverse drug
      reactions (ADRs) in our population, spontaneous reports were collected and
      analysed to ciprofloxacin (the most prescribed fluoroquinolone in our hospital)
      over a period of three and a half years. The pattern of reactions were rash in
      18, severe reactions like Steven Johnson syndrome (SJS) and toxic epidermal
      necrolysis (TEN) in 4, gastritis and diarrhoea in 3, shivering and rigors in 2,
      hemorrhagic purpuric spots in 2 and oedema of eye and lids with topical
      application in 1 patient. Most cases recovered on stoppage of the drug and
      symptomatic treatment. However, one case of SJS and one of TEN proved fatal. Care
      needs to be exercised in their use and they do not appear to be innocuous to
      severe and disturbing ADRs.

PMID- 11229223
TI  - Investigations of thyroid diseases--an update on diagnostic methods.
AB  - Iodine deficiency disorders (IDD) are an important public health problem in
      India. It requires further refinement and improvements in thyroid disease
      diagnosis, especially in the early diagnosis of thyroid malfunctioning and risk
      assessment of autonomously functioning thyroid tissue. Scintigraphy with
      technetium-99m pertechnetate under exogenous or endogenous thyroid stimulating
      hormone (TSH) suppression provides the best results. There has been significant
      improvement in methodology in various laboratory investigations that have
      resulted from the application of newer luminescent techniques and gene technology
      in various thyroid function tests. TSH measurement especially by using second or
      third generation assays has ensured diagnostic accuracy and thyrotropin releasing
      hormone (TRH) test now almost always unnecessary. Determination of
      glycosaminoglycans in urine may become a helpful tool in the follow up of
      endocrine ophthalmopathy. The differentiation of blocking and stimulating TSH
      receptor antibodies is relevant when discrepant results are obtained with respect
      to thyroid function. Some newer imaging agents have been used in thyroid disease
      scintigraphy such as octreotide or in thyroid diseases diagnosis such as
      fluorodeoxyglucose. Both improve the detectability of thyroid cancer metastasis
      especially if radioiodine scan is negative.

PMID- 11229224
TI  - Combining aspirin with angiotensin converting enzyme inhibitors in heart failure:
      how safe is it?
AB  - The above discussion on the interaction of aspirin and ACE inhibitors seems to
      suggest that aspirin in high doses may have adverse interaction with ACE
      inhibitors in patients with heart failure but the data obtained is not sufficient
      or conclusive to recommended omission of aspirin in patients with heart failure.
      This raises a query in the mind of the physician whether to use a combination or
      not? The role of aspirin in the early period after myocardial infarction is well
      established so is the role of ACE inhibitors. Hence in patients with myocardial
      infarction and preserved left ventricular function it would not be wrong to
      administer combination of ACE inhibitors and aspirin. Albeit at a lower dose. In
      patients with large myocardial infarction or heart failure, warfarin may be an
      option but still needs to be documented in large trials. As suggested long term
      use of aspirin after infarction is still ambiguous and may be harmful in patients
      with heart failure with its anticedent side effects. But long term benefits of
      ACE inhibitors in heart failure are well documented. Hence if a choice has to be
      made whether to discontinue either of the two drugs it would be preferable to
      stop the aspirin. To answer the issue of use of aspirin in patients with heart
      failure it would be essential to conduct a double blind randomized trial
      comparing known anti-thrombotic treatment, aspirin and anti-coagulants on
      mortality in patients with heart failure, especially caused by coronary artery
      disease. Such a trial is underway at the present and till the results are
      available it should be left to clinical judgement of the physician whether to
      administer aspirin in patients with heart failure after weighing the benefits
      versus risk.

PMID- 11229225
TI  - Antimalarial chemotherapy: the old and the new perspectives.

PMID- 11229226
TI  - Osteoporosis--approach in Indian scenario.

PMID- 11229227
TI  - An unusual presentation of intramedullary spinal tumour.

PMID- 11229228
TI  - Isolated right ventricular hypertrophic obstructive cardiomyopathy.
AB  - Two cases of isolated hypertrophic cardiomyopathy of right ventricle without any
      involvement of interventricular septum or left ventricle are reported. Two cases
      reported in literature are also reviewed. In these cases symptoms are those of
      left ventricular hypertrophic obstructive cardiomyopathy. Right ventricular
      dominance on clinical examination and electrocardiogram and inspiratory increase
      in intensity of murmur are helpful clues. 2-Dimensional echocardiography with
      Doppler evaluation can confirm the diagnosis noninvasively.

PMID- 11229229
TI  - Massive dose of diazepam poisoning.

PMID- 11229230
TI  - Isolated tuberculous liver abscess.

PMID- 11229231
TI  - Isolated bilateral fifth cranial nerve paralysis with autonomic neuropathy in a
      case of insulin dependent diabetes mellitus.

PMID- 11229232
TI  - Laurence-Moon-Biedl syndrome.

PMID- 11229234
TI  - Retained bile duct stone due to misinterpretation of T-tube cholangiogram.

PMID- 11229233
TI  - Duplication of transverse and descending colon.

PMID- 11229235
TI  - Lipoprotein-A and coronary artery disease in Indians.

PMID- 11229236
TI  - Hyponatremia in HIV infected patient.

PMID- 11229237
TI  - Multisystem organ failure in acute aluminium phosphide poisoning.

PMID- 11229238
TI  - Aggravation of sick sinus syndrome with precipitation of Stokes Adams attacks
      following nimodipine.

PMID- 11229239
TI  - Neurological complications following honey bee sting.

PMID- 11229240
TI  - Cardiopulmonary resuscitation: the Indian scenario.

PMID- 11229241
TI  - Sparfloxacin in tuberculosis.

PMID- 11229242
TI  - Detection of Mycobacterium tuberculosis by polymerase chain reaction in 301
      biological samples--a comparative study.
AB  - A repetitive target sequences of Mycobacterium tuberculosis DNA was amplified by
      polymerase chain reaction (PCR) in a total of 301 clinical samples. Sputum,
      blood, pleural fluid, and bronchial lavage specimen were taken from clinically
      suspected causes of tuberculosis and processed for the diagnosis of tuberculosis
      using a simplified procedure of DNA extraction. PCR was positive in a total of 58
      samples (58/301--19.3%). A significant number of smear and culture negative cases
      of tuberculosis were PCR positive (37/174--21.26%). This finding, combined with
      the absence of either false positive or false negative results reflects the
      greater usefulness of this technique.

PMID- 11229243
TI  - The circadian pattern of ischaemic heart disease events in Indian population.
AB  - A circadian variation of the onset of almost all ischaemic heart disease (IHD)
      manifestations with an increased incidence between 6:00 a.m. to 12:00 noon has
      been reported in several publications during the last decade. This study included
      605 patients of various IHD subgroups, i.e., acute Q-wave myocardial infarction
      (n = 174), unstable angina (n = 266), non-Q myocardial infarction (n = 67), acute
      pulmonary oedema (n = 35) and sudden cardiac death (n = 63) proven to be due to
      IHD by electrocardiogram and/or autopsy. In overall, 33.55% (p < 0.0001) of
      patients had the IHD events with an increased frequency between 6:00 a.m. To
      12:00 noon (2nd quarter of the day.) The distribution in the remaining, 1st 3rd
      and 4th quarters was 22.64%, 20.99% and 22.80%, respectively. Similar circadian
      rhythm (2nd quarter peak) was seen in males (n = 486), females (n = 119),
      patients ages < 60 years (n = 388), patients without past history of IHD (n =
      434) and in those not on any medications (n = 359). However in patients with past
      history of IHD and diabetics, the circadian distribution did not differ from the
      random and the cases were distributed almost evenly in all the four quarters of
      the day. 39.08% of all the acute Q wave myocardial infarction (A-QMI), 33.45% of
      unstable angina and 36.5% of sudden cardiac deaths also occurred between 6:00
      a.m. and 12:00 noon. However 51.42% cases of acute pulmonary oedema were
      encountered in the 4th quarter of the day and patients with non Q-myocardial
      infarction (non-QMI) did not show any particular pattern in relation to circadian
      rhythm. Thus it was inferred that in Indian population too the circadian pattern
      of IHD manifestations are similar to other population studies and morning appears
      to be the time, when the triggers (transient precipitating risk factors) that
      lead to these events are likely to be prominent. Study of these triggers and/or
      early morning pathophysiological changes may go a long way in understanding
      ischaemic heart disease and suggesting possible means of prevention.

PMID- 11229244
TI  - Exercise induced proteinuria as an early indicator of diabetic nephropathy.
AB  - Diabetic nephropathy is a life threatening microvascular complication of diabetes
      characterized by presence of proteinuria and progressive impairment of renal
      function. This study was carried out on 25 patients of diabetes mellitus and 25
      healthy individuals who served as controls. All the persons were asked to perform
      certain programmed amount of exercise and protein excretion rates were measured
      in urine collected over following three periods: just before exercise, just after
      exercise and one hour post exercise. It was observed that basal urinary protein
      excretion rate as well as exercise induced urinary protein levels were
      significantly higher in diabetics than in control (p < 0.001). Values were
      significantly higher in uncontrolled diabetes as compared to those with good
      metabolic control. Urinary protein values were also related to the duration of
      diabetes. Higher values were observed in patients having diabetes of more than 5
      years as compared to those with less than 5 years duration. This test is good and
      easy to perform for early detection and management of diabetic nephropathy which
      is essential to reduce long term morbidity and mortality in diabetics.

PMID- 11229245
TI  - Clinical profile of AIDS: a study at a referral hospital.
AB  - The present study describes the clinical and epidemiological features of 74
      patients with human immunodeficiency virus (HIV) infection who presented to a
      referral hospital. Sixty two patients (83.7%) were diagnosed to have acquired
      immune deficiency syndrome (AIDS). Mean age of the patients was 34.9 +/- 12 years
      and male to female ratio was 3:1. Majority of patients (80%) were from lower
      socio-economic class. Multiple unprotected heterosexual contact with commercial
      sex workers in metropolitan cities of India, mainly Mumbai, was major risk factor
      in 82.1% male patients while most of the females (66.6%) had acquired infection
      from HIV positive husbands. Blood transfusion was the risk factor in 9(12.1%)
      patients. Sixty eight patients were infected with HIV 1, one with HIV 2, and five
      patients with both HIV 1 and HIV 2. Fever and weight loss were the commonest
      presenting symptoms. Tuberculosis, oropharyngeal candidiasis, and interstitial
      pneumonitis were present in 54.8%, 40.3% and 20.9% patients, respectively.
      Fourteen patients (22.5%) had generalised lymphadenopathy. Herpes zoster,
      cryptococcal meningitis, and peripheral neuropathy were infrequent. Response to
      standard antifungal and antitubercular treatment was satisfactory. Kaposi's
      sarcoma, lymphoma, and CNS toxoplasmosis were not found. The clinical
      manifestations of AIDS patients are strikingly different from that in the Western
      countries. It, thus, necessitates setting up of different guidelines for the
      clinical diagnosis and management of AIDS in India.

PMID- 11229246
TI  - A randomized comparison of classical mode of administration of amphotericin B
      with its newer modes of administration in kala-azar.
AB  - One hundred thirty parasitologically confirmed cases of kala-azar were randomly
      divided in two equal treatment groups. Patients in group A were treated by
      infusion with amphotericin B deoxycholate (ABD), 1 mg/kg day on days 1-20 and the
      infusion was given in two hours. Patients in group B were treated by an
      escalating dose of ABD 0.05 mg/kg, 0.1 mg/kg, 0.25 mg/kg, 0.5 mg/kg, 1 mg/kg on
      days 1-5, respectively and then in the same dosage on alternate days. The
      infusion was completed in 6 hours. Total dose of 20 mg/kg remaining the same in
      both the groups, the treatment was completed in 20 days in group A and 43 days in
      group B. Clinical cure (subsidence of fever, improvement in general well being
      and regression in the size of the spleen) and parasitological cure (absence of
      parasites in splenic aspirates at the end of treatment) occurred in all patients
      in both the groups. Sixty four (99%) patients in each group had not relapsed
      clinically and parasitologically within 6 months of follow up and were ultimately
      cured. The two relapsed patients, one in each group were treated with a 20-day
      course of ABD and were cured. Leukocyte count, haemoglobin, serum albumin
      increased (P < 0.05) and ESR, spleen and liver size decreased (P < 0.05) at the
      end of treatment and follow up. Adverse events were similar in both the groups.
      The minimum cost of treatment estimated was Rs. 14,500 in group B and Rs. 10,000
      in Group A. Thus the newer mode of administration was more cost effective.
      CONCLUSION: It was concluded that newer mode of administration of amphotericin B
      was as effective and tolerable as the classical mode of administration and was no
      more toxic. The newer mode of administration of amphotericin B is more cost
      effective and puts lesser burden on hospital staff and is recommended for use in
      kala-azar.

PMID- 11229247
TI  - Investigation of relationship between idiopathic hypercalciuria and urinary
      enzyme activities.
AB  - In patients with uncomplicated idiopathic hypercalciuria renal function is normal
      except for increased renal calcium excretion. In this study, the level of
      fractional urinary enzyme excretion was assessed in relation to calciuria.
      Fourteen patients with a mean age of 5.8 +/- 0.8 years who had daily urinary
      calcium excretion more than 4 mg/kg and with otherwise normal renal function
      tests were included in the study. None of the patients manifested either renal
      calculus or nephrocalcinosis. Fourteen normal children with a mean age of 5.4 +/-
      0.74 were included in the control group. The level of the urinary N-acetyl beta-D
      glucosaminidase (NAG) to creatinine ratio, fractional aspartate aminotransferase
      (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate
      dehydrogenase (LDH) excretion were not significantly different compared to the
      control group (p > 0.05). The patients were subdivided according to the type of
      hypercalciuria. The levels of NAG/creatinine ratio, fractional ALT, AST, ALP, LDH
      excretion were not significantly different in the absorptive type of calciuria
      group compared to the control group (p > 0.05). In conclusion, hypercalciuria
      during childhood which is 6.46 +/- 1.83 mg/kg/day is not related to the levels of
      NAG/creatinine ratio, fractional ALT, AST, ALP and LDH excretion in urine.

PMID- 11229248
TI  - Organophosphate poisoning: predicting the need for ventilatory support.
AB  - The present study evaluated 103 consecutive patients of organophosphate poisoning
      with special reference to the need for ventilatory support. Of 103 patients,
      36(34.95%) required assisted ventilation. The need for ventilatory support was
      significantly more with greater time duration for institution of specific
      treatment, low level of sensorium at admission, pin-point pupils and generalized
      fasciculations, presence of convulsions, presence of respiratory insufficiency at
      admission, and higher initial atropine requirement for atropinization. The study
      also proposes a system of grading of severity, modified from the existing systems
      proposed.

PMID- 11229249
TI  - Pictorial CME.

PMID- 11229250
TI  - In hospital cardiopulmonary resuscitation: a one year study.

PMID- 11229251
TI  - Obstructive sleep apnea syndrome: evaluation of subcritical continuous positive
      airway pressure.
AB  - Twenty eight of 48 patients diagnosed of obstructive sleep apnea syndrome over a
      six month duration opted for CPAP therapy. Half of them were given critical CPAP
      (Group A) and other half were prescribed subcritical level of CPAP (Group B). Re
      evaluation after 3 months revealed that side effects like headache and feeling of
      inconvenience were more in Group A, though beneficial effects were same in both
      groups. It is concluded that subcritical level of CPAP should be adopted to treat
      patients of obstructive sleep apnea syndrome.

PMID- 11229252
TI  - Non-fermenters in urinary tract infection.
AB  - Sixty four (4.4%) strains of non-fermenting gram negative bacteria (NFGNB) were
      isolated out of 1,380 bacterial isolates from 7,784 urine samples, of which 43
      were isolated from male patients and 21 from female patients. P. aeruginosa was
      found to be the commonest (67.2%) followed by A. lwoffi (7.8%), A. anitratus and
      P. acidovorans testosterani (6.2% each), P. maltophilia and P. denitrificans
      (4.8% each), P. putida and P. vesiculare (1.5% each). Forty two(65.6%) of these
      isolates were isolated as pure cultures and 22(34.4%) as predominant organisms.
      Most of these isolates i.e. 50-88.8% were sensitive to Norfloxacin and Ofloxacin
      and 22.2% to 66.6% of these isolates were sensitive to Gentamycin and Cephalexin
      whereas 11.1% of these isolates were sensitive to Co-trimoxazole and Ampicillin.
      All of these isolates were resistant to Penicillin and Tetracycline.

PMID- 11229253
TI  - L-carnitine administration in coronary artery disease and cardiomyopathy.
AB  - Myocardial ischaemia may be defined as a deficiency in cardiac energy supply
      relative to energy demand. In coronary artery disease (CAD), oxygen supply is
      limited due to coronary obstruction so energy production is not enough to meet
      the energy demands for work. Several reports involving about 2500 patients of CAD
      where carnitine was administered for upto 1 year indicate some beneficial
      effects. There is reduction in ischaemia showing reduced ST-segment depression
      and angina, greater effort tolerance and decreased need of cardiac drugs.
      Carnitine can cause overall improvement in cardiac performance in patients with
      CAD as well as in cardiomyopathy. More studies are necessary to demonstrate where
      carnitine can scavenge free radicals apart from its beneficial effect on fatty
      acid metabolism. Side effects of carnitine are mild nausea and vomiting and dose
      upto 2 g/day in 3 divided doses may not have any side effects. Intravenous L
      carnitine acts rapidly and has no side effects.

PMID- 11229254
TI  - Alpha-1 antitrypsin deficiency and chronic obstructive airway disease.

PMID- 11229255
TI  - Implications of lipoprotein abnormalities in Indian patients.

PMID- 11229256
TI  - Poetry in medicine.

PMID- 11229257
TI  - Leopard syndrome with staphylococcal infective endocarditis and stroke in young.

PMID- 11229258
TI  - Hepatic artery aneurysm presenting as pain and mass in the epigastrium.

PMID- 11229259
TI  - Crossed aphasia leading to pure word deafness.
AB  - We report a case of crossed aphasia following a vascular insult of the right
      hemisphere in a middle aged dextral man with subsequent evolution to pure word
      deafness. Development of pure word deafness during recovery from crossed
      Wernickes aphasia is an extremely rare clinical entity. Probably this is the
      first Indian report of this entity.

PMID- 11229260
TI  - Early experience with sparfloxacin in tuberculosis.
AB  - Between December, 1996 and July, 1997, 14 patients of advanced tuberculosis with
      a mean history of prior treatment of 27.4 months were put on oral Sparfloxacin
      200 mg daily. One case each had lumbar spine and pelvic bone disease with
      abscesses, one had subcostal abscess and another had subpulmonic effusion. The
      remaining 10 cases had moderate clinical illness with tuberculosis (meningitis
      (1), massive pneumonia (1)). There was an early dramatic response to the new
      regime, (Sparfloxacin given along with PAS, isoniazide (2), PH with R or Doxy
      (2), SHRZ (4), RH (1), RHZ (2), SHRE (1), and RH + Cy Eth (1)). The only side
      effect complaint was nausea. The response was good (clinical 3+ or more: 11;
      Radiographic > 50%: 11; smear conversion: 12) in 12 cases; one case with
      tuberculous meningitis died seven weeks after a temporary improvement.

PMID- 11229261
TI  - Autologous peripheral stem cell transplant in non-Hodgkin's lymphoma.

PMID- 11229262
TI  - Paracetamol poisoning.

PMID- 11229263
TI  - Unusual complications of varicella infection: myocarditis, incessant ventricular
      tachycardia and transverse myelitis.

PMID- 11229264
TI  - Down's syndrome with unusual manifestations.

PMID- 11229265
TI  - Persistent diabetes mellitus following pituitary adenectomy in a case of
      acromegaly.

PMID- 11229267
TI  - Beta blocker, hepatic functions and confusion.

PMID- 11229266
TI  - Naproxen nephrotoxicity.

PMID- 11229268
TI  - Forgotten role of adrenaline in the management of anaphylactic reaction.

PMID- 11229269
TI  - Need for monitoring adverse drug reactions.

PMID- 11229271
TI  - Coronary artery lesions in Takayasu's arteritis--clinical and angiographic study.
AB  - Two hundred and twenty five patients of Takayasu's arteritis were studied over 13
      years. Male:Female ratio was 1:7. Mean age of the study population was 19 +/- 4
      years. Of these 225 patients, 75 patients had symptoms and/or signs of cardiac
      involvement and these patients were subjected to coronary angiography.
      Significant coronary artery occlusion (i.e. more than 50% narrowing of luminal
      diameter) was present in 9 patients. Incidence of coronary artery lesions in
      Takayasu's arteritis is 12% in this study. The proximal segments of coronary
      arteries were involved while the distal segments were spared. Out of 34 patients
      with angina pectoris, only 3 patients had significant coronary arterial
      narrowing.

PMID- 11229270
TI  - Some unusual and severe forms of adverse drug reactions: a call for setting
      adverse drug reaction monitoring centres.
AB  - Thirty four patients aged 14 to 65 years (18 males and 16 females) admitted to
      the University Hospital with various unusual and severe forms of adverse drug
      reactions were studied. It comprised of toxic epidermal necrolysis in 8 patients,
      systemic vasculitis in 7 of which 3 patients had gangrene of fingers and/or toes,
      severe erosive gastritis in 9 patients, Stevens-Johnson syndrome in 7 patients,
      thrombocytopenic purpura in 2 patients and generalised convulsions in 1 patient.
      Various drugs responsible for causing these adverse drug reactions included
      antibacterials, antimalarials, anticonvulsants, antituberculars and nonsteroidal
      anti-inflammatory drugs. Most of the patients recovered. However, 5 of the 8
      patients having toxic epidermal necrolysis died of which 2 patients had developed
      tetanus as a preterminal event. In view of ongoing addition of newer drugs to the
      therapeutic armamentarium and an increasing incidence of various unusual and
      severe forms of adverse drug reactions, it is our contention that a separate
      adverse drug reaction monitoring cell should be established in every hospital
      setting.

PMID- 11229272
TI  - Tuberculosis in patients with systemic lupus erythematosus.
AB  - In a retrospective analysis of 146 systemic lupus erythematosus (SLE) patients
      seen over a 5 year period, 17 patients of tuberculosis (TB) were identified
      yielding a prevalence rate of 11.6%. The median duration of SLE was 12 months
      (range 2-96 months) and 12/17 patients had disease activity score of more than
      five. The median duration of steroid treatment was 12 months (range 0-96 months)
      and the median cummulative dose of steroid was 7.75 gms (range 0-22.1 gms).
      Pulmonary TB (miliary-5, nonmiliary infiltrates-7 and pleural effusion-2) was the
      commonest type and there was an average diagnostic delay of approximately 1
      month. While, majority of the patients responded adequately to treatment, 1
      patient had a relapse and 1 expired due to a combination of active lupus and
      disseminated TB. Only 1 patient had received prophylactic isoniazid.

PMID- 11229273
TI  - Educational status and dietary fat and anti-oxidant intake in urban subjects.
AB  - To assess correlation of dietary atherogenic and anti-atherogenic factors with
      socio-economic status (SES) we performed nutritional survey among 182 (122 men,
      60 women) randomly selected individuals using 24 hour diet recall and a food
      frequency questionnaire. SES was assessed by educational level which strongly
      correlated with occupational class (r = 0.55) and income levels (r = 0.88). There
      was significant (p < 0.05) positive correlation (r values) of educational level
      with intake of calories (0.55), proteins (0.19), fat (0.45), fat derived energy
      (en%) (0.14), saturated fat en% (0.45), linoleic acid (0.17), vitamin A (0.14),
      vitamin C (0.16), vitamin E (0.44), fruits and vegetables (0.34) and fibre (0.24)
      and negative correlation with intake of linolenic acid (-0.35), monounsaturated
      fat (MUFA) en% (-0.15), polyunsaturated fat (PUFA)/saturated fat (SFA) (-0.33)
      and MUFA/SFA (-0.42). In persons of highest educational level (> 15 years
      education) vs illiterates, the daily intake of SFA (29.1 +/- 15 vs 7.8 +/- 6),
      SFA en% (13.2 +/- 5 vs 6.7 +/- 4), linoleic acid en% (5.4 +/- 3 vs 3.9 +/- 2) and
      n6/n3 (24.0 +/- 58 vs 4.5 +/- 5) was more and intake of linolenic acid en% (0.7
      +/- 1 vs 1.6 +/- 1), MUFA en% (8.6 +/- 7 vs 15.6 +/- 9), PUFA/SFA (0.6 +/- 1 vs
      1.0 +/- 1) and MUFA/SFA (0.7 +/- 1 vs 4.0 +/- 5) was less. Intake of antioxidant
      vitamins A, C and E and fruits and vegetables was significantly more in better
      educated.

PMID- 11229274
TI  - Study of pulmonary function tests in 2000 healthy persons in Gujarat.
AB  - This paper reports the results of spirometric studies done in the state of
      Gujarat in view of deriving the ventilatory norms. The study included a total of
      2000 healthy nonsmoker individuals with 1369 males and 631 females. The study was
      done over the period from September, '92 to July, '93. The observations were
      tabulated, data fed on computers and the normal values for the parameters viz
      peak expiratory flow rate (PEFR), forced expiratory volume--1st second (FEV1) and
      forced vital capacity (FVC) were derived at.

PMID- 11229275
TI  - The impact of infection control on intensive care unit microbial isolates.
AB  - In todays world, good infection control practices in high pressure intensive care
      units is of vital importance. Endogenous infections from the patients own
      microbial flora now cause the majority of nosocomial infections as the exogenous
      infections are curtailed to a large extent with aggressive surveillance and
      prevention of infection. We analysed absolute numbers of microbial isolates as an
      indirect reflection of infection rate in the intensive care unit (ICU) for 6
      months in 1992, 1994 and 1996. We demonstrated that inspite of the total
      admission to the ICU increasing, the impact of infection control is certainly
      felt with strict inforcement of protocols.

PMID- 11229276
TI  - Urinary IgG antibody capture particles adherence test for detecting HIV
      antibodies: a preliminary report.
AB  - It is known that antibodies to HIV are secreted in urine and saliva. IgG antibody
      capture particle adherence test (GACPAT) has been shown to provide accurate
      results for antibodies in urine. The aim of the study was to study the
      sensitivity and specificity of this test in our settings. 114 urine samples were
      collected from both HIV positive and HIV negative patients and were analysed
      using GACPAT. The test has a sensitivity of 92.3% and specificity of 100%. We
      feel that this test has a definite role in our country especially for
      surveillance purposes.

PMID- 11229277
TI  - Role of DNA probes in characterization of pathogenic and non-pathogenic E.
      histolytica.
AB  - Various tests have been described to differentiate the pathogenic and non
      pathogenic types of E. histolytica. Recently DNA hybridization has been described
      to differentiate between the two subtypes. Using common HMC probe the presence of
      E. histolytica in stool was confirmed. Then on the basis of hybridization with
      DNA probe P 145 (pathogenic) and B 133 (non-pathogenic) E. histolytica was
      characterized as being pathogenic and non pathogenic respectively. Out of 137
      patients studied 88 were symptomatic and 49 asymtomatic. 65 patients harboured E.
      histolytica as proved by microscopic examination of stool. Sixty-eight stool
      samples tested positive for DNA hybridization with common HMC probe, this
      included 65 microscopy positive samples and 3 microscopy negative samples. This
      gives a sensitivity of 100% and 96% specificity. All the 68 samples were then
      subjected to hybridization with P 145 and B 133 DNA probes. Out of 88 symptomatic
      patients stool samples of 57 patients were microscopy positive, however 58 were
      positive by common HMC probe and all of these were P 145 (pathogenic) positive
      and B 133 (non-pathogenic) negative. Of the 49 asymptomatic cases 8 were E.
      histolytica positive on microscopy and 10 positive on hybridization with common
      HMC probe and all 10 were P 145 negative and B 133 positive. It can be thus
      concluded that DNA hybridization is a reliable way to differentiate between
      pathogenic and nonpathogenic E. histolytica.

PMID- 11229278
TI  - Pictorial CME. Familial insulin resistance syndrome--Kahn type A with face
      sparing lipo-dystrophy.

PMID- 11229279
TI  - Heparin in haemorrhagic infarction in cerebral venous sinus thrombosis.
AB  - Morbidity and mortality in puerperal cerebral venous thrombosis (CVT) can be
      reduced by arresting the progression of thrombosis using heparin. However,
      conventional dose of heparin requires monitoring of coagulation parameters and
      carries a risk of haemorrhage. The present study involved 56 patients of
      puerperal CVT with CT evidence of haemorrhagic infarction. Twenty nine of these
      patients received low dose heparin till 30th post-partum day or symptomatic
      relief. Their clinical features and severity were similar to 27 patients who did
      not receive heparin. The mortality and morbidity at discharge was significantly
      less (P < 0.001) in heparin treated group. There were no haemorrhagic
      complications. Low dose heparin is safe and effective in cerebral venous
      thrombosis, even with haemorrhagic infarction.

PMID- 11229281
TI  - Spider angiomas are not found in the retina of patients with cirrhosis.
AB  - To determine the prevalence of spider angiomata in patients with cirrhosis, the
      factors influencing them and whether or not they are present in the retina of
      patients with cirrhosis, 93 cirrhotics were studied. Cutaneous spider angioma
      were seen in 19 (20%) patients. All patients with spiders had at least one
      episode of variceal bleeding and had grade III or IV oesophageal varices. Spiders
      were seen more commonly in patients with alcoholic cirrhosis than in those with
      non-alcoholic cirrhosis (53.5% vs 6%, p < 0.001), in patients with Child's C
      cirrhosis than those with Child's A and B cirrhosis (67% vs 4%, p < 0.001).
      However, although spiders were seen more often in patients undergoing
      sclerotherapy than those not, the difference was statistically not significant
      (23% vs 19%, p = NS). Spiders had no association with presence or absence of
      portal hypertensive gastropathy or gastric varices. None of the patients showed
      any abnormality or presence of spiders in the retina. It is concluded that spider
      angiomas are seen more commonly in patients with alcoholic cirrhosis, those with
      more severe liver disease and patients having large oesophageal varices and they
      are not seen in the retina of patients with cirrhosis.

PMID- 11229280
TI  - Antioxidant phenolics and flavonoids in common Indian foods.
AB  - To determine antioxidant phenolics and flavonoids in commonly consumed Indian
      foods we chemically analysed 85 food-stuffs comprising of cereals, pulses, nuts,
      oilseeds, vegetables, fruits and beverages. Total phenolics were measured
      biochemically and flavonoids were measured as a sum of quercetin, kaempferol,
      luteolin and pelargonidin. High flavonoid content (> 100 mg/100 gm) was present
      in tea, coffee, apple, guava, terminalia bark, fenugreek seeds, mustard seeds,
      cinnamon, red chili powder, cloves and turmeric. Medium levels (50-100 mg) were
      found in Indian gooseberry, omum, cumin, cardamom, betel leaf and brandy. Small
      but significant amounts were also present in food-items of large consumption such
      as kidney beans, soyabeans, grapes, ginger, coriander powder, bajra and brinjal.

PMID- 11229282
TI  - Premonitory diagnostic signs and symptoms (scores) of thyroid hypofunction: a
      clinical observation.
AB  - We analyzed signs and symptoms of 79 cases of clinically suspected thyroid
      hypofunctions. There is positive correlation between clinical manifestations and
      thyroid stimulating hormone (TSH). In 33 (41.7%) TSH was ranged between 20-75
      microunit (mu u) suggestive of hypothyroidism, 36 (45.5) were euthyroid. Clinical
      signs and symptoms are scored according to their frequency correlated with serum
      TSH are 4,3,2,1, and 0.5.

PMID- 11229283
TI  - Newer modes of therapy for NIDDM.

PMID- 11229284
TI  - Management of atrial fibrillation.

PMID- 11229286
TI  - World of scientific medicine.

PMID- 11229287
TI  - Post cardiac injury syndrome--one more cause of false positive IgG, IgM
      antibodies in pleural fluid against antigen-60 of Mycobacterium tuberculosis.
AB  - Post cardiac injury syndrome (PCIS) is known to occur following myocardial
      infarction, cardiac surgery, blunt chest trauma, percutaneous left ventricular
      puncture and pace-maker implantation. The diagnosis is one of exclusion. We
      report a case of PCIS following cardiac surgery who showed false positive IgG,
      IgM antibodies to antigen A60 of Mycobacterium tuberculosis in pleural fluid.

PMID- 11229285
TI  - Clinical relevance of reduced bioavailability of rifampicin.
AB  - Bioavailability (BA) of rifampicin (RMP) is a critical factor in successful
      treatment of tuberculosis. The BA of RMP can be reduced by pharmaceutical
      factors, patient factors and drug interactions. Failure of treatment and
      development of drug resistance are potential consequences of reduction in BA and
      it is necessary to understand and control the factors influencing BA of RMP.

PMID- 11229288
TI  - Bifurcated extrahepatic biliary tract.

PMID- 11229289
TI  - Pulmonary alveolar proteinosis with respiratory failure--therapeutic role of
      bronchoscopic and whole lung lavage.

PMID- 11229290
TI  - Senior-Loken syndrome with unusual manifestations.
AB  - The Senior-Loken syndrome, also called Hereditary Renal Retinal Dystrophy is a
      rare disorder that combines a juvenile nephronophthisis-like disease with
      tapetoretinal degeneration. We are reporting a family in which two, possibly
      three siblings are affected by this disorder. In addition to these two documented
      components of the disease, our patients also have unusual manifestations: short
      stature; skeletal abnormalities in the form of kyphoscoliosis, short metacarpals;
      and cutis laxa-unreported so far.

PMID- 11229291
TI  - Progressive multifocal leucoencephalopathy and dementia in an AIDS patient.

PMID- 11229292
TI  - Eosinophilic antral gastritis presenting as pyloric obstruction.

PMID- 11229293
TI  - Autoimmune thrombocytopenic purpura with intracranial haemorrhage.

PMID- 11229294
TI  - Rheumatic heart disease with abdominal lump and clubbing.

PMID- 11229295
TI  - Microalbuminuria--a marker for macrovascular disease.

PMID- 11229296
TI  - Forgotten role of adrenaline in the management of anaphylactic reactions.

PMID- 11229297
TI  - Green coconut water.

PMID- 11229298
TI  - Pregnancy related cerebral venous thrombosis needs exclusion of antiphospholipid
      syndrome.

PMID- 11229299
TI  - Atenolol induced high grade AV block.

PMID- 11229301
TI  - Quinolone resistant enteric fever--problems and remedies.

PMID- 11229300
TI  - Comparison of bioavailability of two brands of rifampicin.

PMID- 11229302
TI  - [Perception of pica and its relationship with iron deficiency by hospital
      physicians in the Paris area].
AB  - OBJECTIVES: To ascertain the attitude of hospital physicians in the Paris area
      concerning pica and its relation to iron deficiency and to compare findings with
      data in the literature. METHODS: An anonymous questionnaire was sent to 174
      department heads of specialty units caring for iron deficiency patients: internal
      medicine (n = 56), hepatogastroenterology (n = 39), hematology (n = 13),
      gynecology and obstetrics (n = 34), pediatrics (n = 32). RESULTS: The overall
      response rate was 40.2%. Ninety-seven percent of all the physicians found pica in
      less than 10% of patients with iron deficiency, and 95.6% considered geophagia as
      the most frequent pica. For 58.5% of the adult medicine practitioners, pica was
      regarded only as a cause of iron deficiency, but for 64.7% of the pediatricians,
      pica was both a cause and a symptom of iron deficiency was not sought in a
      systemic way in 88.6% of the physicians when a cause of iron deficiency was
      known. CONCLUSION: In the majority of the cases, the attitude of hospital
      physicians concerning pica is in disagreement with published data, suggesting
      either epidemiological characteristics specific to the Paris area, or unawareness
      of the phenomenon.

PMID- 11229303
TI  - [Availability of antidotes in French emergency medical aid units].
AB  - OBJECTIVE: To study the availability of antidotes in French emergency medical aid
      units (SAMU). METHODS: The physicians or nurses responsible for antidotes in
      French emergency medical aid units (SAMU) were interviewed by phone. The study
      involved 102 SAMU in metropolitan France. Four answers on availability of 37
      antidotes were possible: the antidote was available in the emergency vehicle used
      for interventions; the antidote was available in the hospital-located SAMU; the
      antidote was available in the referral hospital (emergency unit, intensive care
      unit, operating room, pharmacy); the antidote was not available or not known to
      be available. RESULTS: Adrenaline and atropine were available in all the
      intervention vehicles. Nine other antidotes were available in more than two
      thirds of the vehicles: 30% glucose (101/102), isoprenaline (100/102), dobutamine
      (98/112), sodium bicarbonate (97/102), naloxone (95/102), calcium chloride or
      bicarbonate (89/102), flumazenil (83/102), sodium lactate (77/102), and magnesium
      sulfate (66/102). Among the other antidotes, hydroxocobalamine and propranolol
      were available in 24/102 intervention vehicles and activated charcoal in 22/102.
      Antidigitalic antibodies and 4-methylpyrazole were not available in any vehicle,
      and were available in less than 25% of the hospitals. CONCLUSION: There is a
      great disparity of antidote availability. Certain essential antidotes, for which
      there is no alternative, are not available in emergency intervention vehicles and
      even in the hospital. The SAMU should develop an economically acceptable
      departmental management scheme for exceptional-use antidotes.

PMID- 11229304
TI  - [Palpable mantel cell lymphoma in the breast].
AB  - BACKGROUND: Extranodal involvement is not unusual in mantle cell lymphoma (MCL)
      which accounts for 6% of non-Hodgkin's lymphomas. Simultaneous localization in
      the eyelid and in the breast, as observed in our case, is however exceptional.
      CASE REPORT: Chronic lymphoid leukemia (CLL) was suspected in a 71-year-old woman
      with asthenia, a cervical and axillary nodal enlargement and elevated lymphocyte
      count. Blood immunoflow cytometry analysis, occurrence of rapidly growing tumors
      involving the two breasts and eyelids and cytogenetic and molecular features led
      to the diagnosis of MCL. A very good partial remission was obtained with second
      line polychemotherapy composed of cytarabin, cisplatin and dexamethasone, but
      lasted only 3 months after the end of 6 cycles. DISCUSSION: Primary breast and
      eyelid lymphomas are rare. Such localizations are exceptional in MCL and are
      signs of aggressive disease. Before extra-nodal involvement, MCL may simulate
      banal CLL. Therefore, systematic immunohistochemistry and if necessary molecular
      analysis are useful for early diagnosis of MCL. Prognosis is particularly poor.
      Conventional chemotherapy cannot provide cure of MCL and median survival is 48
      months. For this reason, high-dose chemotherapy with stem cell graft has to be
      discussed in young patients. MCL is currently characterized by Bcl1
      rearrangement, t(11-14) translocation and cyclin D1 overexpression among small B
      cell lymphomas in recent REAL- and WHO-classifications.

PMID- 11229305
TI  - [Tuberculosis discovered in a patient with Sweet's syndrome].

PMID- 11229307
TI  - [Association of Streptococcus bovis meningitis and colonic diverticulitis:
      favorable effect of corticotherapy?].

PMID- 11229306
TI  - [Cerebral infarction in a patient consuming MaHuang extract and guarana].

PMID- 11229308
TI  - [Gestational diabetes: an alternative to insulin therapy?].

PMID- 11229309
TI  - [Management of health and environmental risk: the case of nitrates].

PMID- 11229310
TI  - [Hyperlipidemias: new data and new concepts].
AB  - STATINS: Strategy for management of patients displaying hyperlipidemia has
      changed since the the first statin has been launched in France more than ten
      years ago. Following the first primary and secondary prevention studies conducted
      with hyperlipidemic subjects, results have been extended to patients with
      cholesterol levels within normal range both in primary (AFCAPS/TexCAPS) and
      secondary (CARE) prevention. Drug therapy has been simplified with targets
      tailored to the patient's risk. OPEN QUESTIONS: Despite these important results
      from intervention studies with statins, other crucial questions remain. Among
      these questions the first one concerns the possibility that cardiovascular
      benefits demonstrated with statins are also partly due to other (pleiotropic)
      effects. This was first hypothesised when statins were proven to be efficacious
      after short term treatments (one year in the regression studies). The second
      question is whether we can extend the benefit observed in populations included in
      published trials to primary prevention of stroke and to the groups less well
      represented in previous trials including women, elderly patients. The current
      trends and economic strains of every health care systems have focused on evidence
      based medicine and cost-efficacy studies. ROLE OF TRIGLYCERIDES: Beyond LDL
      cholesterol there is clear emergence of a role of triglyceride in cardiovascular
      disease as well as new data on pathophysiology of the so-called reverse
      cholesterol transport. Recent trials including patients with hypertriglyceridemia
      as well as a decline of the benefit observed in hypertriglyceridemic patients
      strongly suggest that the use of statins may have its own limitation. IMPORTANCE
      OF DIET: Finally, translating results of recent trials in clinical practice
      remains a challenge for treating physicians who face poor compliance and
      difficulties in implementing diet in patients.

PMID- 11229311
TI  - [Inhalation spacer devices in childhood asthma: is utilization easy?].
AB  - IMPROVED DRUG DELIVERY: Spacer devices improve the pulmonary deposition of drugs
      delivered from pressurized metered-dose inhalers because they decrease the
      diameter of the aerosol particles. Spacer devices are the best delivery system of
      inhaled drugs in children younger than 8 years. TECHNICAL ASPECTS: Small volume
      spacer devices, with inspiratory and expiratory valves, are particularly
      interesting to use. The use of a facemask is only recommended in the youngest and
      the oldest have to breathe through the mouth piece. Electrostatism is generated
      from the plastic walls of the spacer devices and decreases the drug delivery.
      Using a metallic spacer device or washing a plastic spacer device with a domestic
      detergent, without rinsing with water nor rubbing the walls, avoids this problem.
      OPTIMAL USE: Spacer devices are not generics. Each drug has a specific behaviour
      in a spacer device. Correct inhalatory technique has to be checked at each visit
      for an optimal efficacy of the treatment.

PMID- 11229312
TI  - [Measurement of the carotid intima-media thickness. An innovative technique for
      assessing cardiovascular risk].
AB  - ASSESSMENT OF CARDIOVASCULAR RISK: Measurement of the intima-media thickness in
      the carotid artery is optimized by coupling high-resolution ultrasonography with
      automatic data processing systems, allowing improved precision. Although the
      optimal site of measurement remains controversial (common carotid, bifurcation,
      internal carotid), there appears to be a consensus on need for bilateral
      automatic measurement. The intima-media thickness is considered a marker of
      atheromatous disease and its diffusion. This parameter probably integrates the
      deleterious effect of different cardiovascular risk factors accumulated over
      decades. In addition, several prospective observation studies have reported a
      positive relationship between measurement of the intima-media thickness of the
      carotid artery and risk of cardiovascular events (myocardial infarction and
      stroke). DETECTION AID: Although the results issuing from epidemiology
      observation studies are still too preliminary, to evaluate the positive and
      negative predictive value for occurrence of clinical events in relation to
      different levels of thickness, this simple rapid and noninvasive measurement
      could be a useful tool for subjects with high cardiovascular risk. PERSPECTIVES:
      Measurement of arterial parameters, determined by high-resolution
      ultrasonography, will probably shortly become an integral part of the evaluation
      strategies for cardiovascular risk. Future comparative studies will provide an
      assessment of the comparative predictive value of these different parameters
      (quantitative structural analysis versus quantitative and qualitative analysis of
      the structure versus structural and functional analysis of the arteries).

PMID- 11229313
TI  - [Diaphragmatic paralysis: diagnosis by TM-sonography].

PMID- 11229314
TI  - [Role of bronchospasm in development of bronchial obstruction in chronic
      bronchitis].
AB  - AIM: To clarify the role of bronchospasm in impairment of bronchial permeability
      in chronic bronchitis. MATERIALS AND METHODS: Lung capacity (LC), forced lung
      capacity (FLC), forced expiration volume for 1 second (FEV1), FEV1/LC%, peak
      volume rate (PVS), maximal volume expiration rate (MVER) at the level of 25, 50
      and 75% of LC were measured in 62 patients with chronic obstructive bronchitis
      before and after inhalation of 1 dose of berotec and 1 dose of atrovent. RESULTS:
      Bronchospasm was present in 42% of the patients, being the only cause of
      obstruction in 5% of patients. Other reasons added in 37%. Bronchospasm
      contribution to obstruction reached 21-40, 41-80, 81-100% in 5, 10 and 27% of
      patients, respectively. CONCLUSION: An important role of bronchospasm in
      development of bronchial obstruction in chronic bronchitis is proved.

PMID- 11229315
TI  - [Clinical course of chronic bronchitis in Chernobyl wreckers].
AB  - AIM: To characterize clinical symptoms of chronic bronchitis (CB) in Chernobyl
      wreckers. MATERIAL AND METHODS: 71 CB male Chernobyl wreckers exposed to low-dose
      radiation and 43 control patients were examined and treated in a specialized
      hospital in 1988-1996. Clinical features of CB were investigated by clinical
      (complaints, history, objective examination), laboratory (total blood count,
      biochemical and immunological blood picture, coagulogram) and instrumental
      (fibrobronchoscopy, x-ray, radiometry, spirography) findings with further
      statistical processing. RESULTS: Chernobyl wreckers more frequently had
      neurocirculatory asthenia and hemoptysis. The latter was caused by bronchial
      mucosa atrophy. In chronic non-obstructive bronchitis they exhibited mild
      bronchoobstruction on the distal level. Laboratory indices showed no essential
      changes. CONCLUSION: Chernobyl wreckers have a more severe course of CB.

PMID- 11229316
TI  - [Significance and features of MLC reaction in histocompatibility determination of
      donor and recipient in allogenic bone marrow transplantation to patients with
      hematological malignancies].
AB  - AIM: To characterize mixed lymphocyte culture (MLC) reaction used for
      determination of donor-recipient compatibility before bone marrow transplantation
      to patients with hematological malignancies and to assess the reaction
      significance. MATERIAL AND METHODS: The analysis was made of compatibility
      testing in MLC standard reaction performed in 134 patients with hematological
      malignancies with HLA-A, -B identical donors-sibs and in 5 patients with haploid
      identical donors. RESULTS: Out of 134 patients, 22(91%) appeared compatible to
      donor sibs in MLC reaction, 12(9%) patients were incompatible. Mean RR for MLC
      compatible couples made up: in RvD direction 77 +/- 0.17%, DvR 2.61 +/- 0.32%.
      93% of RR values ranged from +15 to -15%, the rest--from +25% to -25%. Bone
      marrow transplantation was made in 83 patients. Graft retention was observed in
      77(93%) patients. Acute and chronic graft versus host reaction developed in 15
      and 17 patients, respectively. CONCLUSION: An optimal protocol is proposed for
      examination of compatibility donor-recipient in MLC reaction in patients with
      hematological malignancies. It is intended for allogenic bone marrow
      transplantation in hematological departments.

PMID- 11229317
TI  - [Rheumatoid arthritis in combination with primary biliary liver cirrhosis].

PMID- 11229318
TI  - [Sarcoidosis with hyperprolactinemic galactorrhea].

PMID- 11229319
TI  - [Administration of alphacalcidol (alpha-D3-Teva) for osteoporosis prevention].

PMID- 11229320
TI  - [Chronic obstructive pulmonary diseases and osteoporosis].

PMID- 11229321
TI  - Molecular cloning of cDNA encoding N-acetylglucosaminyltransferase II from
      Arabidopsis thaliana.
AB  - N-acetylglucosaminyltransferase II (GnTII, EC 2.4.1.143) is a Golgi enzyme
      involved in the biosynthesis of glycoprotein-bound N-linked oligosaccharides,
      catalysing an essential step in the conversion of oligomannose-type to complex N
      glycans. GnTII activity has been detected in both animals and plants. However,
      while cDNAs encoding the enzyme have already been cloned from several mammalian
      sources no GnTII homologue has been cloned from plants so far. Here we report the
      molecular cloning of an Arabidopsis thaliana GnTII cDNA with striking homology to
      its animal counterparts. The predicted domain structure of A. thaliana GnTII
      indicates a type II transmembrane protein topology as it has been established for
      the mammalian variants of the enzyme. Upon expression of A. thaliana GnTII cDNA
      in the baculovirus/insect cell system, a recombinant protein was produced that
      exhibited GnTII activity.

PMID- 11229323
TI  - The ethics of using animals in science.

PMID- 11229322
TI  - Midterm results of arthroscopic co-planing of the acromioclavicular joint.
AB  - BACKGROUND: There has been recent concern about long-term morbidity associated
      with arthroscopic co-planing of the acromioclavicular joint in the treatment of
      impingement syndrome. OBJECTIVE: The purpose of this study was to assess the
      results of the co-planing procedure, special attention being paid to
      acromioclavicular joint morbidity. METHODS: The study included 56 patients who
      were operated on by the senior author. Outcomes were evaluated both objectively
      and subjectively through physical examinations and telephone surveying. Each
      patient had subacromial decompression at the time of the index surgery. Other
      concomitant arthroscopic procedures included rotator cuff repair and labral
      debridement or repair. RESULTS: Average follow-up was 4 years (range, 2-7 years).
      Thirty-five (95%) of 37 patients had no subjective pain and no objective
      tenderness to direct palpation or compression of the acromioclavicular joint. The
      joint was not clinically hypermobile in comparison with that on the opposite side
      in any patient. In all, 95% of patients had good or excellent results in terms of
      the University of California at Los Angeles Shoulder Score. Of the 2 patients who
      did have pain and tenderness at the acromioclavicular joint, both had had
      multiple operations on their shoulders before the index procedure. Nineteen
      patients were not examined clinically but did complete a telephone survey; these
      19 patients were not symptomatic at the acromioclavicular joint. CONCLUSIONS: To
      fully treat impingement syndrome, the surgeon should remove osteophytes under the
      lateral clavicle and medial acromion. With good technique, the surgeon can leave
      the anterior, posterior, and superior acromioclavicular joint capsule intact. We
      conclude that for appropriate clinical indications, beveling the inferior 20% to
      25% of the clavicle to make it co-planar with the decompressed acromion is safe
      and is not an etiologic factor in acromioclavicular joint pain or instability.

PMID- 11229324
TI  - Index of suspicion. Case 3. Diagnosis: Guillain-Barre Syndrome.

PMID- 11229325
TI  - Index of suspicion. Case 4. Diagnosis: Lyme disease.

PMID- 11229326
TI  - Index of suspicion. Case 5. Diagnosis: Congenital diaphragmatic hernia.

PMID- 11229327
TI  - Index of suspicion. Case 6. Diagnosis: Candidiasis.

PMID- 11229328
TI  - [Remembering Dr. Endre Kertesz, specialty chief (1921-2000)].

PMID- 11229329
TI  - Historical Vignette: Hiroshima, 1955.

PMID- 11229330
TI  - Remarks on some of Ziegler's statements.

PMID- 11229331
TI  - Redefining azoospermia and its implications.

PMID- 11229332
TI  - Defining and predicting the poor responder!

PMID- 11229333
TI  - The scope and limitations of "FISH" for preimplantation genetic diagnosis.

PMID- 11229334
TI  - Are the basic assumptions correct--is endometriosis a progressive, self
      destructive disease?

PMID- 11229335
TI  - Are the basic assumptions correct--is endometriosis a progressive, self
      destructive disease?

PMID- 11229336
TI  - The DNA-repair gene MGMT and the clinical response of gliomas to alkylating
      agents.

PMID- 11229337
TI  - The DNA-repair gene MGMT and the clinical response of gliomas to alkylating
      agents.

PMID- 11229338
TI  - The DNA-repair gene MGMT and the clinical response of gliomas to alkylating
      agents.

PMID- 11229339
TI  - The DNA-repair gene MGMT and the clinical response of gliomas to alkylating
      agents.

PMID- 11229340
TI  - Markers of myocardial damage and inflammation in unstable coronary artery
      disease.

PMID- 11229341
TI  - Adjuvant chemotherapy for completely resected non-small-cell lung cancer.

PMID- 11229342
TI  - Adjuvant chemotherapy for completely resected non-small-cell lung cancer.

PMID- 11229343
TI  - Adjuvant chemotherapy for completely resected non-small-cell lung cancer.

PMID- 11229344
TI  - Mucosal shedding of human herpesvirus 8.

PMID- 11229345
TI  - Mucosal shedding of human herpesvirus 8.

PMID- 11229346
TI  - Mucosal shedding of human herpesvirus 8.

PMID- 11229347
TI  - Narcolepsy and the HLA system.

PMID- 11229348
TI  - Treatment of ciguatera poisoning with gabapentin.

PMID- 11229349
TI  - Chronic pelvic pain: clinical dilemma or clinician's nightmare.

PMID- 11229350
TI  - Antioxidants: strategies for interventions in aging and age-related diseases. A
      workshop sponsored by the National Institute on Aging and by the Office of
      Dietary Supplements.
AB  - The role of free radicals in aging has been a long-standing theory that has now
      been extended to include both reactive oxygen and nitrogen species. The original
      concepts that overwhelming oxidative stress depleted antioxidants and thus
      damaged intracellular targets is being supplanted by the hypothesis that the
      reactive species play an essential role in signal transduction. The concept that
      the cell establishes a redox tone that is altered during the aging process places
      the oxidative and nitrosative modifications that occur during aging in a new and
      exciting context. Some highlights of this recent workshop convened by The
      National Institute on Aging and the Office of Dietary Supplements at the National
      Institutes of Health are discussed.

PMID- 11229351
TI  - Strategies for evaluation of signaling pathways and transcription factors altered
      in aging.
AB  - Aging is characterized by an accumulation of oxidative injury to DNA, RNA,
      proteins, lipids, and carbohydrates. In addition to damage, oxidative stress can
      initiate cell signaling cascades that modulate cell function, growth, and death.
      Aging and two common age-related diseases, diabetes mellitus and atherosclerosis,
      may share common oxidant-related signaling pathways that lead to abnormal
      transcription factor activation and ultimately to cellular dysfunction,
      degeneration, or death. This review will focus on approaches to evaluate key
      redox-sensitive signaling pathways and the transcription factors altered by
      diabetes, atherosclerosis, and aging.

PMID- 11229352
TI  - Role of nitric oxide in the regulation of acute and chronic inflammation.
AB  - Recent studies by a number of different laboratories have implicated nitric oxide
      (NO) as an important modulator of a variety of acute and chronic inflammatory
      disorders. A hallmark of inflammation is the adhesion of leukocytes to post
      capillary venular endothelium and the infiltration of leukocytes into the tissue
      interstitium. Leukocyte adhesion and infiltration is known to be dependent on
      interaction of the leukocytes with the endothelial cell surface via a class of
      glycoproteins collectively known as endothelial cell adhesion molecules (ECAMs).
      Several recent studies suggest that NO may modulate cytokine-induced ECAM
      expression in cultured endothelial cells in vitro by regulating the activation of
      nuclear transcription factor kappa B (NF-kappaB). This discussion reviews some of
      the more recent studies that assess the role of the different NOS isoforms on the
      inflammatory response in vivo.

PMID- 11229353
TI  - Tocopherol-binding proteins: their function and physiological significance.
AB  - The present review is a continuation of earlier essays on the uptake mechanisms
      and the biological function of vitamin E. There are eight naturally occurring
      homologues of vitamin E, which differ in their structure and in biological
      activity in vivo and in vitro. Various studies have suggested that after normal
      gastrointestinal absorption of dietary vitamin E specific mechanisms favor the
      preferential accumulation of one of its homologues, alpha-tocopherol, in the
      human body. This process is thought to be mediated in part by the alpha
      tocopherol transfer protein (alpha-TTP) in the liver cytoplasm. The mechanism and
      pathway by which alpha-TTP specifically incorporates alpha-tocopherol into plasma
      lipoproteins is not yet fully understood. Because alpha-tocopherol is widely
      distributed in tissues in various concentrations but alpha-TTP resides only in
      liver, its role as intracellular carrier of alpha-tocopherol seems unlikely.
      However, recent data indicate that a system of alpha-tocopherol-binding proteins
      is involved in these processes that favor the localization of alpha-tocopherol at
      the sites where it is required. The current status of the evidence for the
      regulation of alpha-tocopherol levels and their impact on cellular signaling is
      discussed.

PMID- 11229354
TI  - Mechanisms of vitamin E regulation: research over the past decade and focus on
      the future.
AB  - This paper discusses the developments in human vitamin E research since 1990. New
      methodologies such as the use of stable isotopes, advances in vitamin E
      measurements, and isolation and cloning of specific alpha-tocopherol binding
      proteins have facilitated investigation of alpha-tocopherol absorption,
      metabolism, and transport in humans in vivo. Changes in food production in the
      United States and dietary intake impacted vitamin E availability and intake.
      Epidemiologic and therapeutic studies have pointed to its role in disease
      prevention and in healing processes. Specific molecular functions of alpha
      tocopherol have been the most recent and surprising new findings and are an
      important area for future experimentation. Given the aging of the American
      population and the potential role for alpha-tocopherol in preventive medicine,
      the study of the molecular functions of vitamin E promises to provide some of the
      most exciting discoveries of the next decade.

PMID- 11229355
TI  - Metabolic, metallic, and mitotic sources of oxidative stress in Alzheimer
      disease.
AB  - Cell bodies of neurons at risk of death in Alzheimer disease (AD) have increased
      lipid peroxidation, nitration, free carbonyls, and nucleic acid oxidation. These
      oxidative changes are uniform among neurons and are seen whether or not the
      neurons display neurofibrillary tangles and, in fact, are actually reduced in the
      latter case. In consideration of this localization of damage, in this review, we
      provide a summary of recent work demonstrating some key abnormalities that may
      initiate and promote neuronal oxidative damage. First, mitochondrial
      abnormalities might be the source of reactive oxygen species yielding perikaryal
      oxidative damage. The common 5-kb deletion mitochondrial (mt)DNA subtype was
      greatly increased in the AD cases, but only in neurons at risk. The importance of
      such mitochondrial abnormalities to oxidative stress was indicated by a high
      correlation coefficient between the extent of the mtDNA increase and RNA
      oxidative damage (r2 = 0.87). Nonetheless, because mitochondria in AD do not show
      striking oxidative damage, as one would expect if they were the direct producer
      of free radical species, we suspected that abnormal mitochondria supply a key
      reactant that, once in the cytoplasm, releases radicals. One such reactant,
      hydrogen peroxide, (H2O2), abundant in mitochondria, can react with iron via the
      Fenton reaction to produce.OH. To demonstrate this directly using a modified
      cytochemical technique that relies on the formation of mixed valence iron
      complexes, we found that redox-active iron is associated with vulnerable neurons.
      Interestingly, removal of iron was completely affected by using deferroxamine,
      after which iron could be rebound to re-establish lesion-dependent catalytic
      redox reactivity. Characterization of the iron-binding site suggests that binding
      is dependent on available histidine residues and on protein conformation. Taken
      together with our previous studies showing abnormalities in the iron homeostatic
      system including heme oxygenase, iron regulatory proteins 1 and 2, ceruloplasmin,
      and dimethylargininase, our results indicate that iron misregulation could play
      an important role in the pathogenesis of AD and therefore chelation therapy may
      be a useful therapeutic approach. Finally, we wanted to determine the proximal
      cause of mitochondrial abnormalities. One interesting mechanisms involves re
      entry into the cell cycle, at which point organellokinesis and proliferation
      results in increased mitochondria. Supporting this, we have considerable in vivo
      and in vitro evidence for mitotic disturbances in AD and its relationship with
      the pathogenesis of AD.

PMID- 11229356
TI  - Ironing-out mechanisms of neuronal injury under hypoxic-ischemic conditions and
      potential role of iron chelators as neuroprotective agents.
AB  - Iron is the most abundant transition metal in the brain, where it functions as an
      important cofactor in a host of vital metabolic processes and plays an absolutely
      essential role in cell viability. Free iron is also very toxic when present in
      high concentrations, thus placing this essential metal at the core of neurotoxic
      injury in a number of neurological disorders. The pivotal role of iron in
      cellular homeostasis, including its latent toxicity, necessitates a tight
      regulation of iron metabolism. Oxygen and iron appear to play an important role
      in iron homeostasis. They appear to exert their homeostatic role by modulating
      the proteins involved in a complex interplay between iron sensing, transport, and
      storage. These key regulatory proteins include ferritin (intracellular storage),
      transferrin (extracellular transport), transferrin receptor, and iron regulatory
      protein (sensor of intracellular iron concentration). The interplay of iron and
      oxygen is most intriguing in the setting of stroke, where hypoxia and free iron
      appear to interact in causing the subsequent neuronal death.

PMID- 11229357
TI  - Model for aging in the basal forebrain cholinergic system.
AB  - A key component of the cognitive deficits associated with aging is the loss of
      function of cholinergic neurons in the basal forebrain due to neuronal losses and
      decreased cholinergic function of spared neurons. A model to mimic one aspect of
      this phenomenon is to kill cholinergic neurons selectively in the basal forebrain
      via administration of the immunotoxin IgG-192-saporin. Here we discuss apoptotic
      regulators, such as nerve growth factor, in age-associated changes present in the
      cholinergic system and the role of the NF-kappaB signaling system in cellular
      commitment to apoptosis. We also examine the age-associated decline in intrinsic
      response mechanisms, which may account for the age-associated reduction in
      recovery from both acute and chronic insults to the central nervous system.

PMID- 11229358
TI  - The roles of dopamine oxidative stress and dopamine receptor signaling in aging
      and age-related neurodegeneration.
AB  - Aging is accompanied by a decline of functions controlled by the central
      dopaminergic system, such as reduced locomotor activity, motivation, impairment
      of memory formation, and learning deficits. The molecular mechanisms underlying
      age-related impairment of dopaminergic functions are unknown. Current literature
      and our own recent work, which are reviewed and summarized in the present paper,
      suggest that dopamine oxidative stress and its subsequent signaling may
      contribute to the aging of dopaminergic system.

PMID- 11229359
TI  - Sensitivity of FRDA lymphoblasts to salts of transition metal ions.
AB  - Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease
      resulting from decreased expression of the nuclear-encoded mitochondrial protein,
      frataxin. FRDA patients have characteristic iron deposits and dysfunction of
      mitochondrial enzymes in the heart. Inactivation of the frataxin homologue in
      yeast causes dysregulation of both mitochondrial iron levels and iron export.
      Previously, we have observed sensitivity of FRDA fibroblasts to FeCl3 and
      hydrogen peroxide, results consistent with the hypothesis that FRDA cells may
      experience increased Fenton chemistry. To determine whether the sensitivity of
      FRDA cells to transition metal ions is a general or specific property, we have
      compared the sensitivity of lymphoblasts from FRDA patients and healthy controls
      to the transition metal salts CoCl2, CuSO4 FeCl3 FeSO4, MnCl2, and ZnCl2. FRDA
      lymphoblasts were significantly more sensitive to FeCl3 and MnCl2 than control
      cells. However, there were no significant differences observed in sensitivity to
      CoCl2, CuSO4, FeSO4 and ZnCl2 in the concentration ranges studied. Thus, the
      sensitivity of FRDA lymphoblasts exposed to transition metals appears to be
      specific, and could be relevant to the pathophysiological mechanism, which is
      discussed.

PMID- 11229360
TI  - Ginkgo biloba abolishes aggression in mice lacking MAO A.
AB  - Mice deficient in monoamine oxidase A (MAO A) have increased brain levels of
      serotonin (5-HT) and norepinephrine and show enhanced aggression. We used MAO A
      knock-out (KO) mice as a model to study the effect of ginkgo biloba (EGb) on
      aggression. When EGb was administered to MAO A KO mice, their aggressive behavior
      in resident-intruder confrontations was reduced to levels seen in wild types. EGb
      did not affect the locomotive behavior of MAO A KO mice, which suggests that its
      effects on aggression were not due to sedation. EGb caused a significant 16.9%
      decrease in [3H]ketanserin binding to 5-HT2A receptors in the frontal cortex of
      MAO A KO mice but did not change the receptor affinity for [3H]ketanserin. This
      suggests that the antiaggressive effect of EGb may be mediated by 5-HT2A
      receptors and that EGb may be developed as a novel antiaggressive agent.

PMID- 11229361
TI  - (R)-alpha-lipoic acid reverses the age-associated increase in susceptibility of
      hepatocytes to tert-butylhydroperoxide both in vitro and in vivo.
AB  - Hepatocytes were isolated from young (3-5 months) and old (24-28 months) rats and
      incubated with various concentrations of tert-butylhydroperoxide (t-BuOOH). The t
      BuOOH concentration that killed 50% of cells (LC50) in 2 hr declined nearly two
      fold from 721 +/- 32 microM in cells from young rats to 391 +/- 31 microM in
      cells from old rats. This increased sensitivity of hepatocytes from old rats may
      be due, in part, to changes in glutathione (GSH) levels, because total cellular
      and mitochondrial GSH were 37.7% and 58.3% lower, respectively, compared to cells
      from young rats. Cells from old animals were incubated with either (R)- or (S)
      lipoic acid (100 microM) for 30 min prior to the addition of 300 microM t-BuOOH.
      The physiologically relevant (R)-form, a coenzyme in mitochondria, as opposed to
      the (S)-form significantly protected hepatocytes against t-BuOOH toxicity.
      Dietary supplementation of (R)-lipoic acid [0.5% (wt/wt)] for 2 weeks also
      completely reversed the age-related decline in hepatocellular GSH levels and the
      increased vulnerability to t-BuOOH as well. An identical supplemental diet fed to
      young rats did not enhance the resistance to t-BuOOH, indicating that antioxidant
      protection was already optimal in young rats. Thus, this study shows that cells
      from old animals are more susceptible to oxidant insult and (R)-lipoic acid,
      after reduction to an antioxidant in the mitochondria, effectively reverses this
      age-related increase in oxidant vulnerability.

PMID- 11229362
TI  - Protein disulfide isomerase in Alzheimer disease.
AB  - There is a great deal of evidence that places oxidative stress as a proximal
      event in the natural history of Alzheimer disease (AD). In addition to increased
      damage, there are compensatory increases in the levels of free sulfhydryls,
      glucose-6-phosphate dehydrogenase, and NAD(P)H:quinone oxidoreductase 1. To
      investigate redox homeostasis further in AD, we analyzed protein disulfide
      isomerase (PDI), a multifunctional enzyme, which catalyzes the disruption and
      formation of disulfide bonds. PDI plays a pivotal role in both secreted and cell
      surface-associated protein disulfide rearrangement. In this study, we show that
      PDI specifically localizes to neurons, where there is no substantial increase in
      AD compared to age-matched controls. These findings indicate that the neurons at
      risk of death in AD do not show a substantial change in PDI to compensate for the
      increased sulfhydryls and reductive state found during the disease. This suggests
      that, despite compensatory reductive changes in AD, the level of PDI is
      sufficiently high physiologically in neurons to accommodate a more reducing
      environment.

PMID- 11229363
TI  - Lycopene synergistically inhibits LDL oxidation in  combination with vitamin E,
      glabridin, rosmarinic acid, carnosic acid, or garlic.
AB  - Several lines of evidence suggest that oxidatively modified low-density
      lipoprotein (LDL) is atherogenic, and that atherosclerosis can be attenuated by
      natural antioxidants, which inhibit LDL oxidation. This study was conducted to
      determine the effect of tomato lycopene alone, or in combination with other
      natural antioxidants, on LDL oxidation. LDL (100 microg of protein/ml) was
      incubated with increasing concentrations of lycopene or of tomato oleoresin
      (lipid extract of tomatoes containing 6% lycopene, 0.1% beta-carotene, 1% vitamin
      E, and polyphenols), after which it was oxidized by the addition of 5
      micromol/liter of CuSO4. Tomato oleoresin exhibited superior capacity to inhibit
      LDL oxidation in comparison to pure lycopene, by up to five-fold [97% vs. 22%
      inhibition of thiobarbituric acid reactive substances (TBARS) formation, and 93%
      vs. 27% inhibition of lipid peroxides formation, respectively]. Because tomato
      oleoresin also contains, in addition to lycopene, vitamin E, flavonoids, and
      phenolics, a possible cooperative interaction between lycopene and such natural
      antioxidants was studied. A combination of lycopene (5 micromol/liter) with
      vitamin E (alpha-tocopherol) in the concentration range of 1-10 micromol/liter
      resulted in an inhibition of copper ion-induced LDL oxidation that was
      significantly greater than the expected additive individual inhibitions. The
      synergistic antioxidative effect of lycopene with vitamin E was not shared by
      gamma-to-cotrienol. The polyphenols glabridin (derived from licorice), rosmarinic
      acid or carnosic acid (derived from rosemary), as well as garlic (which contains
      a mixture of natural antioxidants) inhibited LDL oxidation in a dose-dependent
      manner. When lycopene (5 micromol/liter) was added to LDL in combination with
      glabridin, rosmarinic acid, carnosic acid, or garlic, synergistic antioxidative
      effects were obtained against LDL oxidation induced either by copper ions or by
      the radical generator AAPH. Similar interactive effects seen with lycopene were
      also observed with beta-carotene, but, however, to a lesser extent of synergism.
      Because natural antioxidants exist in nature in combination, the in vivo
      relevance of lycopene in combination with other natural antioxidants was studied.
      Four healthy subjects were administered a fatty meal containing 30 mg of lycopene
      in the form of tomato oleoresin. The lycopene concentration in postprandial
      plasma was elevated by 70% in comparison to plasma obtained before meal
      consumption. Postprandial LDL isolated 5 hr after meal consumption exhibited a
      significant (p < 0.01) reduced susceptibility to oxidation by 21%. We conclude
      that lycopene acts synergistically, as an effective antioxidant against LDL
      oxidation, with several natural antioxidants such as vitamin E, the flavonoid
      glabridin, the phenolics rosmarinic acid and carnosic acid, and garlic. These
      observations suggest a superior antiatherogenic characteristic to a combination
      of different natural antioxidants over that of an individual one.

PMID- 11229364
TI  - Characterization of human and mouse peroxiredoxin IV: evidence for inhibition by
      Prx-IV of epidermal growth factor- and p53-induced reactive oxygen species.
AB  - The aim of this study was to identify and characterize human and mouse Prx-IV. We
      identified mouse peroxiredoxin IV (Prx-IV) by virtue of sequence homology to its
      human ortholog previously called AOE372. Mouse Prx-IV conserves an amino-terminal
      presequence coding for signal peptide. The amino acid sequences of mature mouse
      and human Prx-IV share 97.5% identity. Phylogenetic analysis demonstrates that
      Prx-IV is more closely related to Prx-I/-II/-III than to Prx-V/-VI. Previously,
      we mapped the mouse Prx-IV gene to chromosome X by analyzing two sets of
      multiloci genetic crosses. Here we performed further comparative analysis of
      mouse and human Prx-IV genomic loci. Consistent with the mouse results, human Prx
      IV gene localized to chromosome Xp22.135-136, in close proximity to SAT and
      DXS7178. A bacterial artificial chromosome (BAC) clone containing the complete
      human Prx-IV locus was identified. The size of 7 exons and the sequences of the
      splice junctions were confirmed by PCR analysis. We conclude that mouse Prx-IV is
      abundantly expressed in many tissues. However, we could not detect Prx-IV in the
      conditioned media of NIH-3T3 and Jurkat cells. Mouse Prx-IV was specifically
      found in the nucleus-excluded region of cultured mouse cells. Intracellularly,
      overexpression of mouse Prx-IV prevented the production of reactive oxygen
      species induced by epidermal growth factor or p53. Taken together, mouse Prx-IV
      is likely a cytoplasmic or organellar peroxiredoxin involved in intracellular
      redox signaling.

PMID- 11229365
TI  - Detection of thioredoxin in gastric cancer: association with histological type.
AB  - Thioredoxin (TRX) is a redox-active protein with multiple intra- and
      extracellular functions. This protein exists ubiquitously in all life forms, from
      primitive living cells, such as Escherichia coli and yeast, to higher mammals.
      Recently, augmentation of the expression and transcription level of TRX has been
      reported in tumors of various organs. In this study, we examined the expression
      of TRX in gastric cancer with respect to its histological type and depth of
      invasion. The association with cell proliferation was also studied. Results of
      histochemical analysis of surgical specimens as well as cytochemical analysis and
      Northern blot analysis of gastric cancer cell lines indicated that TRX is
      predominantly expressed in undifferentiated type gastric cancer rather than in
      the differentiated type. Neither the depth of tumor invasion nor cell
      proliferation significantly determined the staining intensity for TRX.

PMID- 11229366
TI  - Redox modulation of chloroplast DNA replication in Chlamydomonas reinhardtii.
AB  - We constructed a plasmid probe containing DNA sequences unique for chloroplast
      (Cp) genome and nuclear genome of Chlamydomonas reinhardtii. Using this probe and
      quantitative Southern blot analyses, we determined the content ratio of Cp
      DNA/nuclear DNA in total DNA isolated from cells grown in different conditions.
      Algal cells grown photoheterotrophically with acetate as an added carbon source
      contain the highest amount of Cp DNA compared with cells grown in other
      conditions tested. We investigated the effect of nitrogen limitation, 5
      fluorodeoxyuridine treatment, cadmium exposure, photoautotrophic growth, and
      heterotrophic growth in darkness. The change in the Cp/nuclear DNA ratio in cells
      shifted from one growth condition to another depended on cell division; Cp DNA
      content in undivided cells remained constant. Therefore, the reduction of Cp DNA
      content was attributed by under replication rather than selective degradation of
      Cp DNA. Cells with low Cp DNA content often contained less reduced glutathione,
      suggesting the possible effect of redox status. Low Cp DNA content was detected
      in cells treated with inhibitors that block electron flow of photosystems and in
      mutants with PS I defective phenotype. On the basis of these data, we propose
      that in C. reinhardtii, Cp DNA replication be modulated by redox status.

PMID- 11229367
TI  - Redox aspects of Bcl-2 function.
AB  - The oncogene Bcl-2 has attracted recent research attention as recognition of the
      importance of Bcl-2 control over apoptosis commitment in disease development and
      clinical response to therapy has been targeted for pharmacological intervention.
      Much of the basic science research regarding Bcl-2 has focused on the role that
      Bcl-2 plays in directly regulating mitochondrial function. This has come about
      because of Bcl-2's localization to mitochondrial membranes and its reported
      interaction with the mitochondrial megachannel. During the time that the
      mitochondrial function of Bcl-2 was being investigated, a smaller, yet
      potentially as important, role for Bcl-2 was being pursued by investigators who
      were following up the initial study of Bcl-2 knockout mice. These mice expressed
      a phenotype consistent with that of mice exposed to chronic oxidative stress.
      This research into the redox aspects of Bcl-2 function has led to a hypothesis
      that Bcl-2-expressing cells have enhanced antioxidant capacities that suppress
      oxidative stress signals generated during the initiation phase of many apoptotic
      pathways. This review will further develop the idea of Bcl-2's role in regulating
      cellular redox pathways associated with apoptosis, as well as integrate recently
      reported evidence that ties the antioxidant effects of Bcl-2 to mitochondrial
      function, thereby unifying both mitochondrial and redox aspects of Bcl-2
      function.

PMID- 11229368
TI  - Genetic and metabolic control of the mitochondrial transmembrane potential and
      reactive oxygen intermediate production in HIV disease.
AB  - Redox mechanims play important roles in replication of human immunodeficiency
      virus type 1 (HIV-1) and cellular susceptibility to apoptosis signals. Viral
      replication and accelerated turnover of CD4+ T cells occur throughout a prolonged
      asymptomatic phase in patients infected by HIV-1. Disease development is
      associated with steady loss of CD4+ T cells by apoptosis, increased rate of
      opportunistic infections and lymphoproliferative diseases, disruption of energy
      metabolism, and generalized wasting. Such pathological states are preceded by:
      (i) depletion of intracellular antioxidants, glutathione (GSH) and thioredoxin
      (TRX), (ii) increased reactive oxygen species (ROS) production, and (iii) changes
      in mitochondrial transmembrane potential (deltapsi(m)). Disruption of deltapsi(m)
      appears to be the point of no return in the effector phase of apoptosis. Viral
      proteins Tat, Nef, Vpr, protease, and gp120, have been implicated in initiation
      and/or intensification of oxidative stress and disruption of deltapsi(m). Redox
      sensitive transcription factors, NF-kappaB, AP-1, and p53, support expression of
      viral genes and proinflammatory lymphokines. ROS regulate apoptosis signaling
      through Fas, tumor necrosis factor (TNF), and related cell death receptors, as
      well as the T-cell receptor. Oxidative stress in HIV-infected donors is
      accompanied by increased glucose utilization both on the cellular and organismal
      levels. Generation of GSH and TRX from their corresponding oxidized forms is
      dependent on NADPH provided through the pentose phosphate pathway of glucose
      metabolism. This article seeks to delineate the genetic and metabolic bases of
      HIV-induced oxidative stress. Such understanding should lead to development of
      effective antioxidant therapies in HIV disease.

PMID- 11229369
TI  - Redox aspects of signaling by catecholamines and their metabolites.
AB  - This review covers certain novel aspects of catecholamine signaling in neurons
      that involve redox systems and synaptic plasticity. The redox hypothesis suggests
      that one important factor in neurocomputation is the formation of new synapses
      and the removal of old ones (synaptic plasticity), which is modulated in part by
      the redox balance at the synapse between reactive oxygen species (ROS) (such as
      hydrogen peroxide and the nitric oxide radical) and neuroprotective antioxidants
      (such as ascorbate, glutathione, and catecholamines). Catecholamines, in
      particular dopamine, which signals positive reinforcement, may play a key role in
      this activity. Dopamine has powerful antioxidant properties by several separate
      mechanisms-direct ROS scavenging, activation of the synthesis of antioxidant
      proteins, and possibly via dismuting complexes with iron inside endosomes or in
      catecholaminergic synaptic vesicles. This may contribute to synaptic growth and
      reinforcement-directed learning. On the other hand, catecholamines are easily
      oxidized to toxic quinones on the neuromelanin pathway. This might contribute
      under certain circumstances to synaptic deletion. Evidence is presented that
      abnormalities in this system may contribute to the pathogenesis of Parkinson's
      disease and schizophrenia.

PMID- 11229370
TI  - Implications of inducible nitric oxide synthase expression and enzyme activity.
AB  - We summarize here our current knowledge about inducible nitric oxide synthase
      (NOS) activity in human diseases and disorders. As basic research discovers more
      and more effects of low or high concentrations of NO toward molecular and
      cellular targets, successful therapies involving inhibition of NO synthesis or
      application of NO to treat human diseases are still lacking. This is in part due
      to the fact that the impact of NO on cell function or death are complex and often
      even appear to be contradictory. NO may be cytotoxic but may also protect cells
      from a toxic insult; it is apoptosis-inducing but also exhibits prominent anti
      apoptotic activity. NO is an antioxidant but may also compromise the cellular
      redox state via oxidation of thiols like glutathione. NO may activate specific
      signal transduction pathways but is also reported to inhibit exactly these, and
      NO may activate or inhibit gene transcription. The situation may even be more
      complicated, because NO, depending on its concentration, may react with oxygen or
      the superoxide anion radical to yield reactive species with a much broader
      chemical reaction spectrum than NO itself. Thus, the action of NO during
      inflammatory reactions has to be considered in the context of timing and duration
      of its synthesis as well as stages and specific events in inflammation.

PMID- 11229372
TI  - Antioxidants: their role in pregnancy and miscarriage.
AB  - The aim of this study was to examine the role of antioxidants within the normal
      menstrual cycle, in healthy pregnancy, and in women suffering first-trimester
      miscarriage. The antioxidants chosen comprised of two from peripheral blood
      plasma thiol and ceruloplasmin-and two extracellular parameters-superoxide
      dismustase (SOD) and red cell lysate thiol. We found that antioxidant levels
      varied little throughout the menstrual cycle. Pregnancies that went successfully
      to term were associated with increased levels of ceruloplasmin and SOD early in
      the first trimester. These changes were thought to offer the cell protection from
      the damage caused by the increased oxidative stress associated with pregnancy.
      First-trimester miscarriage was associated with significantly reduced levels of
      SOD. A subgroup of patients who miscarried in their first pregnancy, but whose
      second pregnancies were successful, had higher levels of plasma thiol and
      significantly reduced levels of red cell lysate thiol in the on-going pregnancy
      compared to levels at the time of miscarriage. Miscarriage and pregnancy appear
      to be associated with increased oxidative stress. In a successful pregnancy,
      however, changes occurred within the peripheral blood that offered protection
      from oxidant attack.

PMID- 11229373
TI  - Synthesis, characterization, and substitution chemistry of
      [Bu4N]2[W6Cl8(OSO2CF3)6]. A versatile precursor for axially substituted clusters
      containing the (W6Cl8)4+ core.
AB  - The new cluster [Bu4N]2[W6Cl8(OSO2CF3)6] (1) has been prepared and structurally
      characterized. This material is an effective precursor for the generation of
      cluster ions with the general formula [W6C18L6]n (L = Cl-, Br-, I-, NCS-, NCO-,
      NCSe-, and O=PPh3; n = 2- or 4+). The last three clusters are new. The products
      have been characterized by IR spectroscopy, NMR spectroscopy, and FAB mass
      spectrometry. In addition to 1, the products [Bu4N]2[W6C18(NCS)6] (5) and
      [Bu4N]2[W6C18(NCO)6] (7) were structurally characterized. Crystal data for 1:
      space group, P2(1/c) (No. 14); a = 11.116(5) A; b = 27.952(1) A; c = 24.516(1) A;
      beta = 95.182(9) degrees; V = 7586.3(5) A3; Z = 4. Crystal data for 5: space
      group, P2(1/n) (No. 14); a = 11.3323(9) A; b = 12.3404(9) A; c = 44.583(3) A;
      beta = 97.089(1) degrees ; V = 6187.1(7) A3; Z = 4. Crystal data for 7: space
      group, P1 (No. 2); a = 11.8009(8) A; b = 11.9332(8) A; c = 11.9522(8) A; alpha =
      77.904(1) degrees; beta = 95.182(9) degrees; gamma = 62.574(1) degrees V =
      1450.5(2) A3; Z = 1.

PMID- 11229371
TI  - Novel role of oxidants in the molecular mechanism of action of peroxisome
      proliferators.
AB  - Peroxisome proliferators are nongenotoxic rodent carcinogens that act as tumor
      promoters by increasing cell proliferation; however, their precise mechanism of
      action is not well understood. Oxidative DNA damage caused by leakage of hydrogen
      peroxide (H2O2) from peroxisomes was hypothesized initially as the mechanism by
      which these compounds cause liver tumors. It seems unlikely that oxidants of
      peroxisomal origin explain the mechanism of action of peroxisome proliferators
      because treatment with these compounds in vivo does not lead to increased H2O2
      production. On the other hand, Kupffer cell-derived oxidants, such as superoxide,
      may play a role in initiating tumor nerosis factor-alpha (TNF-alpha) production
      that leads to hepatocyte proliferation. Peroxisome proliferators have been shown
      to activate Kupffer cells both in vitro and in vivo, and the use of Kupffer cell
      inhibitors such as methyl palmitate and dietary glycine have demonstrated that
      Kupffer cells are responsible for hepatocyte proliferation by mechanisms involve
      TNF-alpha. Moreover, peroxisome proliferators activate the transcription factor
      NF-kappaB, one of the major regulators of TNF-alpha expression, in Kupffer cells.
      Importantly, activation of NF-kappaB by peroxisome proliferators was shown to be
      oxidant-dependent, leading to the hypothesis that oxidants of Kupffer cell origin
      are involved in the mechanism of action. Many of the effects of peroxisome
      proliferators, including peroxisome induction and hepatomegaly, involve the
      peroxisome proliferator-activated receptor-alpha (PPARalpha). Recently, it was
      shown that peroxisome proliferator-induced cell proliferation and tumors require
      the PPARalpha. However, PPARalpha is not involved in TNF-alpha production by
      Kupffer cells because it is not expressed in this cell type. How it is involved
      in liver tumor remains unclear and one possible explanation is that both Kupffer
      cell TNF-alpha and parenchymal cell PPARalpha are required. Collectively, recent
      data are consistent with the hypothesis that oxidants play a role in signaling
      hepatocellular proliferation due to peroxisome proliferators via activation of NF
      kappaB and incrase in mitogenic cytokines such as TNF-alpha.

PMID- 11229374
TI  - Synthesis and characterization of pyridine amide cation radical complexes of
      iron: stabilization due to coordination with low-spin iron(III) center.
AB  - We reported the synthesis and characterization of peptide complexes of low-spin
      iron(III) [Fe(bpb)(py)2][ClO4] (1) and Na[Fe(bpb)(CN)2] (2) [H2bpb = 1,2
      bis(pyridine-2-carboxamido)benzene; py = pyridine], where iron is coordinated to
      four nitrogen donors in the equatorial plane with two amide nitrogen anions and
      two pyridine nitrogen donors (Ray, M.; Mukherjee, R.; Richardson, J. F.;
      Buchanan, R. M. J. Chem. Soc., Dalton Trans. 1993, 2451). Chemical oxidation of 2
      and a new low-spin iron(III) complex Na[Fe(Me6bpb)(CN)2].H2O (4) [synthesized
      from a new iron(III) complex [Fe(Me6bpb)(py)2][ClO4] (3) (S = 1/2)] [H2Me6bpb =
      1,2-bis(3,5-dimethylpyridine2-carboxamido)-4,5-dimethylbenzene) by (NH4)2Ce(NO3)6
      afforded isolation of two novel complexes [Fe(bpb)-(CN)2] (5) and
      [Fe(Me6bpb)(CN)2].H2O (6). All the complexes have been characterized by
      physicochemical techniques. While 1-4 are brown/green, 5 and 6 are violet/bluish
      violet. The collective evidence from infrared, electronic, Mossbauer, and 1H NMR
      spectroscopies, from temperature-dependent magnetic susceptibility data, and from
      cyclic voltammetric studies provides unambiguous evidence that 5 and 6 are low
      spin iron(III) ligand cation radical complexes rather than iron(IV) complexes.
      Cyclic voltammetric studies on isolated oxidized complexes 5 and 6 display
      identical behavior (a metal-centered reduction and a ligand-centered oxidation)
      to that observed for complexes 2 and 4, respectively. The Mossbauer data for 6
      are almost identical with those of the parent compound 4, providing compelling
      evidence that oxidation has occurred at the ligand in a site remote from the iron
      atom. Strong antiferromagnetic coupling (-2J > or = 450 cm(-1)) of the S = 1/2
      iron atom with the S = 1/2 ligand pi-cation radical leads to an effectively S = 0
      ground state of 5 and 6. The oxidized complexes display 1H NMR spectra (in CDCl3
      solution), characteristic of diamagnetic species.

PMID- 11229375
TI  - Mycoflora and mycotoxins in Brazilian black pepper, white pepper and Brazil nuts.
AB  - A wide range of field and storage fungi were isolated from black pepper, white
      pepper and Brazil nut kernels from Amazonia. A total of 42 species were isolated
      from both peppers. Aspergillus flavus and A. niger were isolated more frequently
      from black than from white pepper. Other potential mycotoxigenic species isolated
      included: A. ochraceus, A. tamarii, A. versicolor, Emericella nidulans and
      Chaetomium globosum, Penicillium brevicompactum, P. citrinum, P. islandicum and
      P. glabrum. Species isolated from pepper for the first time were Acrogenospora
      sphaerocephala, Cylindrocarpon lichenicola, Lacellinopsis sacchari, Microascus
      cinereus, Petriella setifera and Sporormiella minima. Seventeen species were
      isolated from Brazil nut kernels. A. flavus was the dominant species followed by
      A. niger. P. citrinum and P. glabrum were the only penicillia isolated. Species
      isolated for the first time included Acremonium curvulum, Cunninghamella elegans,
      Exophiala sp., Fusarium oxysporum, Pseudoallescheria boydii, Rhizopus oryzae,
      Scopulariopsis sp., Thielavia terricola and Trichoderma citrinoviride.
      Considerably more metabolites were detected from black than white pepper in
      qualitative analyses. Chaetocin, penitrem A, and xanthocillin were identified
      only from black pepper, and tenuazonic acid was identified from both black and
      white pepper. Aflatoxin G2, chaetoglobosin C, and spinulosin were identified from
      poor quality brazil nuts. Aflatoxin B1 and B2 were also only detected in poor
      quality brazil nuts at concentrations of 27.1 micrograms kg-1 and 2.1 micrograms
      kg-1 respectively (total 29.2 micrograms kg-1).

PMID- 11229376
TI  - New South Wales: report of the working party on medicinal cannabis.

PMID- 11229377
TI  - Mandatory drug testing and treatment for welfare recipients in Ontario, Canada.

PMID- 11229378
TI  - Contraception in general practice before teenage pregnancy. Ambition may be best
      contraception.

PMID- 11229379
TI  - Contraception in general practice before teenage pregnancy. Intrauterine device
      may not be suitable method of contraception for teenagers.

PMID- 11229380
TI  - Importance of injecting vaccines into muscle. Parenteral vaccines must be given
      subcutaneously in patients with congenital bleeding disorders.

PMID- 11229381
TI  - Evidence is not (yet) enough for evidence based policy for chlamydia screening.

PMID- 11229382
TI  - Risk factors for breast cancer. Smoking may be important.

PMID- 11229383
TI  - Treating bipolar affective disorder. ECT is effective.

PMID- 11229384
TI  - Overweight and adenocarcinoma of the oesophagus.

PMID- 11229385
TI  - Nurses are also punished for having mental health problems.

PMID- 11229386
TI  - All children deserve to know the truth.

PMID- 11229387
TI  - University-industry partnership.

PMID- 11229388
TI  - Climate change.     It's official: humans are behind most of global warming.

PMID- 11229389
TI  - Quantum optics.     Atomic squeeze play stops light cold.

PMID- 11229390
TI  - Nobel prize. Researcher overlooked for 2000 Nobel.

PMID- 11229391
TI  - Neuroscience.     Glia tell neurons to build synapses.

PMID- 11229392
TI  - Germany. National centers urged to team up, compete.

PMID- 11229394
TI  - National Science Foundation. Transition rumor targets Colwell.

PMID- 11229393
TI  - Plant biology. Xylem may direct water where it's needed.

PMID- 11229396
TI  - High-energy physics. New collider sees hints of quark-gluon plasma.

PMID- 11229395
TI  - Clinical medicine. FDA to release data on gene therapy trials.

PMID- 11229397
TI  - Clinical research. Company plans to bank human DNA profiles.

PMID- 11229398
TI  - Cancer research. U.K. cancer funders may unite.

PMID- 11229399
TI  - Questioning the treatment for   ADHD.

PMID- 11229400
TI  - Questioning the treatment for ADHD.

PMID- 11229401
TI  - Biochemistry of   neurodegeneration.

PMID- 11229402
TI  - Artificial intelligence.     Autonomous mental development by robots and animals.

PMID- 11229403
TI  - Role of importin-beta in coupling Ran to downstream targets in microtubule
      assembly.
AB  - The guanosine triphosphatase Ran stimulates assembly of microtubule asters and
      spindles in mitotic Xenopus egg extracts. A carboxyl-terminal region of the
      nuclear-mitotic apparatus protein (NuMA), a nuclear protein required for
      organizing mitotic spindle poles, mimics Ran's ability to induce asters. This
      NuMA fragment also specifically interacted with the nuclear transport factor,
      importin-beta. We show that importin-beta is an inhibitor of microtubule aster
      assembly in Xenopus egg extracts and that Ran regulates the interaction between
      importin-beta and NuMA. Importin-beta therefore links NuMA to regulation by Ran.
      This suggests that similar mechanisms regulate nuclear import during interphase
      and spindle assembly during mitosis.

PMID- 11229404
TI  - Chemistry. Aromatic metal clusters.

PMID- 11229406
TI  - Meeting the energy challenge.

PMID- 11229405
TI  - Protein design of an HIV-1 entry inhibitor.
AB  - Human immunodeficiency virus type-1 (HIV-1) membrane fusion is promoted by the
      formation of a trimer-of-hairpins structure that brings the amino- and carboxyl
      terminal regions of the gp41 envelope glycoprotein ectodomain into close
      proximity. Peptides derived from the carboxyl-terminal region (called C-peptides)
      potently inhibit HIV-1 entry by binding to the gp41 amino-terminal region. To
      test the converse of this inhibitory strategy, we designed a small protein,
      denoted 5-Helix, that binds the C-peptide region of gp41. The 5-Helix protein
      displays potent (nanomolar) inhibitory activity against diverse HIV-1 variants
      and may serve as the basis for a new class of antiviral agents. The inhibitory
      activity of 5-Helix also suggests a strategy for generating an HIV-1 neutralizing
      antibody response that targets the carboxyl-terminal region of the gp41
      ectodomain.

PMID- 11229407
TI  - Venezuelan response to   Yanomamo book.

PMID- 11229408
TI  - International pharmacists meet in Vienna.

PMID- 11229410
TI  - Polymorphic ventricular tachycardia after use of intravenous amiodarone for
      postoperative junctional ectopic tachycardia.

PMID- 11229409
TI  - A word of caution.

PMID- 11229411
TI  - Wolff-Parkinson-White syndrome and myocardial infarction.

PMID- 11229412
TI  - Neurogenic stunned myocardium in a patient with metastatic brain tumors.

PMID- 11229413
TI  - Congenital pulmonary stenosis revealed by myocardial infarction.

PMID- 11229414
TI  - Myocardial infarction after aspirin cessation in stable coronary artery disease
      patients.

PMID- 11229415
TI  - Recurrent early coronary heart disease.

PMID- 11229416
TI  - Research on purines and their receptors comes of age.

PMID- 11229417
TI  - NK1 receptor antagonists--are they really without effect in the pain clinic?

PMID- 11229418
TI  - Homocysteine, fibrinogen, and lipoprotein(a) levels are simultaneously reduced in
      patients with chronic renal failure treated with folic acid, pyridoxine, and
      cyanocobalamin.
AB  - Ischemic heart disease and other complications of atherosclerosis are the usual
      cause of death in patients with chronic renal failure. Important factors
      associated with early onset of atherosclerosis in these patients are
      hyperhomocysteinemia, hyperfibrinogenemia, and elevated levels of lipoprotein(a)
      (Lp(a)). Folic acid (15 mg/d), pyridoxine (150 mg/d), and cyanocobalamin (1
      mg/wk) were administered for 4 weeks in 21 patients receiving dialysis, and a
      simultaneous, statistically significant reduction in the concentration of
      homocysteine, fibrinogen, and Lp(a) was found. A positive correlation between
      decreasing homocysteine and fibrinogen levels was also noted. The parameters
      studied approached presupplementation values 6 months after vitamins were
      discontinued. The results suggest that vitamin supplementation has a favorable
      effect on risk factors of atherosclerosis in patients with renal failure and that
      interactions may exist between homocysteine, fibrinogen, and Lp(a).

PMID- 11229419
TI  - Urinary epinephrine and norepinephrine interrelations with obesity, insulin, and
      the metabolic syndrome in Hong Kong Chinese.
AB  - The metabolic syndrome is characterized by a clustering of cardiovascular risk
      factors including type 2 diabetes mellitus, hypertension, dyslipidemia, and
      obesity. Elevated plasma insulin and urinary norepinephrine (noradrenaline) and
      reduced urinary epinephrine (adrenaline) excretion are associated with obesity in
      Caucasian populations. We examined the interrelationships between obesity, plasma
      insulin, and urinary catecholamine excretion in Chinese subjects with various
      components of the metabolic syndrome. A total of 577 Chinese subjects (aged 38 +/
      10 years; 68% with type 2 diabetes mellitus, hypertension, dyslipidemia,
      obesity, and/or albuminuria and 32% healthy subjects) were studied, all of whom
      had a plasma creatinine less than 150 micromol/L. The blood pressure, height,
      weight, waist and hip circumference, and fasting plasma glucose, insulin, lipid,
      and creatinine levels were measured. A 24-hour urine sample was collected for
      measurement of albumin and catecholamine excretion. The body mass index (BMI) and
      waist circumference were used as measures of general and central obesity,
      respectively. The insulin resistance index was estimated by the calculated
      product of fasting plasma insulin and glucose concentrations. Patients with an
      increasing number of components of the metabolic syndrome (type 2 diabetes
      mellitus, hypertension, dyslipidemia, obesity, and/or albuminuria) were more
      obese, hyperglycemic, dyslipidemic, and albuminuric and had higher blood
      pressure, plasma insulin, insulin resistance indices, and 24-hour urinary
      norepinephrine excretion but lower urinary epinephrine output (all P < .005).
      Increasing quintiles of BMI in the whole population or waist circumference in
      both sexes were associated with increasing trends for adverse lipid profiles,
      plasma insulin, insulin resistance indices, and urinary norepinephrine excretion
      but a decreasing trend for urinary epinephrine output (all P < .001). There were
      close associations between age, obesity, blood pressure, fasting plasma glucose,
      lipid, insulin, insulin resistance indices, and urinary catecholamine excretion.
      Using stepwise multiple regression analysis (all P < .001), 34% of the
      variability of the BMI and 45% of that of the waist circumference were
      independently related to gender (waist higher in males and BMI higher in
      females), increased plasma insulin, triglyceride, and urinary norepinephrine
      excretion, and decreased high-density lipoprotein (HDL) cholesterol and urinary
      epinephrine output. In Chinese subjects with different manifestations of the
      metabolic syndrome, hyperinsulinemia, insulin resistance, elevated
      norepinephrine, and reduced epinephrine excretion were closely associated with
      general and central obesity. Based on these findings, we postulate that complex
      interactions between the insulin and sympathoadrenal systems may lead to the
      development of obesity and the metabolic syndrome.

PMID- 11229420
TI  - Effect of serotonin reuptake inhibitor on syndrome development in obese
      hyperglycemic mice (Umea ob/ob).
AB  - These experiments tested the effect of 10 to 30 mg, citalopram/kg body weight on
      food intake, weight increase, and blood glucose levels in young obese
      hyperglycemic mice (Umea ob/ob). A leptin defect in ob/ob mice results in
      hyperphagia, hyperglycemia, and increased body weight compared with normal mice.
      Citalopram had no effect on weight increase in ob/ob mice aged 3 to 10 weeks,
      when the weight increase is most rapid. Citalopram reduced the weight increase at
      the age 10 to 19 weeks. Food intake reaches a maximum at age 7 to 10 weeks and
      then decreases. The reduction was more rapid in citalopram-treated mice. The
      weight of feces paralleled the food intake. Citalopram treatment had no effect on
      serum insulin levels in 15-week-old mice. Blood sugar values in fed mice reached
      a peak at age 7 weeks (21.7 +/- 1.7 mmol/L in controls and 22.3 +/- 1 mmol/L in
      citalopram-treated mice). After that, blood sugar values decreased. The decrease
      was more pronounced in citalopram-treated mice (P < .01 compared with controls).
      Blood glucose levels were lower at ages 12 to 15 weeks in female ob/ob control
      mice (13.6 +/- 2.5 mmol/L v 19.0 +/- 0.6 mmol/L in male control mice; P < .05).
      The effect of citalopram was the same in male and female mice. There was a close
      correlation between accumulated food intake and blood glucose values in
      individual animals. At age 3 to 10 weeks, ob/ob mice have a high beta-cell
      proliferation rate, and they have large islets of Langerhans. This was not
      affected by citalopram treatment. Our findings show that the serotonergic system
      plays a role as a regulator of food intake over shorter periods, and this is also
      true in the absence of leptin.

PMID- 11229421
TI  - Altered myosin light-chain phosphorylation in resting platelets from
      premenopausal women with diabetes.
AB  - Gender-related differences in the rate of coronary heart disease (CHD) between
      premenopausal women and men are greatly diminished in women with diabetes
      mellitus (DM). This may be related, in part, to altered platelet function in
      premenopausal diabetic women. Hyperglycemia may contribute to increase platelet
      aggregation through enhancement of oxidative stress, increased nitric oxide (NO)
      destruction, and increased myosin light-chain (MLC) phosphorylation (MLC-P).
      Accordingly, we investigated functional and biochemical parameters of platelet
      function in 32 women (14 premenopausal and postmenopausal controls and 18 age
      matched patients with DM); platelet MLC-P and cyclic guanosine monophosphate
      ([cGMP] reflecting NO) were assessed. Other parameters including age, body mass
      index (BMI), waist to hip ratio, total cholesterol, and platelet count were not
      different in the control and diabetic groups. In the premenopausal women,
      baseline MLC-P was lower in women with DM versus the control group (P = .02). GMP
      levels were similar in the two groups at baseline (22.7 +/- 3 fmol/mL in controls
      v 23.1 +/- 3 fmol/mL in diabetic subjects) and 3 minutes after insulin exposure.
      The platelet content of ascorbic acid (AA), an endogenous antioxidant compound,
      was elevated in premenopausal women with DM (P = .02) compared with the controls.
      Despite similar estradiol (beta,E2) levels, platelets of premenopausal women with
      DM exhibited reduced MLC-P. This paradoxic difference may be accounted for by an
      increase in platelet AA, as this suggests decreased platelet oxidative stress in
      this patient population. These observations indicate that an altered redox state
      and associated MLC-P of platelets does not contribute to enhanced platelet
      aggregation and CHD in premenopausal women with DM.

PMID- 11229422
TI  - Apolipoprotein E gene polymorphism is related to metabolic abnormalities, but
      does not influence erythrocyte membrane lipid composition or sodium-lithium
      countertransport activity in essential hypertension.
AB  - The aim of this study was to analyze the influence of the apolipoprotein E (apoE)
      gene polymorphism on insulin resistance and plasma lipid composition of essential
      hypertensive patients. A secondary objective was to analyze if differences
      regarding plasma lipids had an effect on the erythrocyte membrane lipid
      composition and the activity of the erythrocyte membrane sodium-lithium
      countertransport. We studied 128 untreated nondiabetic essential hypertensive
      patients enrolled from our outpatient clinic. We considered as hyperinsulinemic
      all subjects having more than 80 mU/L of plasma insulin 120 minutes after a 75-g
      oral glucose intake. The number of hyperinsulinemic subjects among carriers of
      the epsilon4 allele was higher that in epsilon4 noncarrier subjects (13 of 19 v45
      of 109, P < .05; odds ratio [OR], 3.08; confidence interval [CI], 0.99-10.57).
      Plasma insulin at baseline and plasma insulin and glucose at 120 minutes after
      overload was higher in carriers of the epsilon4 allele (respectively, 17.5 +/-
      6.9 v 12.4 +/- 4.9 mU/L, P < .01; 111.9 +/- 39.9 v 88.7 +/- 48.2, P < .05; and
      143.8 +/- 29.3 v 121.2 +/- 30.8 mg/dL, P < .005). Subjects with the epsilon4
      allele had a plasma lipid profile more atherogenic than those without this
      allele. This profile was mainly characterized by higher levels of low-density
      lipoprotein (LDL) cholesterol (150.1 +/- 31.2 v 133.0 +/- 34.3 mg/dL, P < .05)
      and very-low-density lipoprotein (VLDL) triglycerides (134.7 +/- 85.5 v 99.2 +/-
      68.8 mg/dL, P < .05) and by lower levels of high-density lipoprotein (HDL)
      cholesterol (41.8 +/- 10.7 v 50.0 +/- 14.7 mg/dL, P < .05). There were no
      differences between groups regarding erythrocyte membrane cholesterol or
      phospholipids composition and sodium-lithium countertransport (SLC) activity.

PMID- 11229423
TI  - Fasting medium chain acyl-coenzyme A dehydrogenase--deficient children can make
      ketones.
AB  - Medium chain acyl-coenzyme A dehydrogenase (MCAD) deficiency classically presents
      as hypoketotic hypoglycemia. Under-production of ketones has been presumed to be
      the cause of hypoketosis, but this has never been proven. Stable isotope dilution
      studies of ketone kinetics were performed on three well children with homozygous
      985G MCAD deficiency using 1,3-13C2 sodium acetoacetate and 1,2,3,4-13C4 sodium 3
      hydroxybutyrate to ascertain the rates of ketone production, interconversion, and
      use. All children were fasted for 9 to 11.5 hours before the beginning of the
      study period. Euglycemia was maintained in all cases. Ketone kinetics were
      calculated using a two-accessible pool model and showed normal ketone production
      in all three children compared with published control data from children fasted
      for a similar length of time. There is no evidence for underproduction or overuse
      of ketones in these MCAD-deficient children, at least when they are well. We
      propose that another factor, such as fever, may be required to reduce ketone
      production and result in the biochemical phenotype recognized in unwell children.

PMID- 11229424
TI  - Hemorrheologic abnormalities in defined primary dyslipoproteinemias with both
      high and low atherosclerotic risks.
AB  - Dyslipoproteinemias are associated with hemorrheologic abnormalities (elevated
      fibrinogen concentration, higher viscosity of plasma and blood). Epidemiologic
      data suggest that not only elevated lipoprotein concentrations (eg, low-density
      lipoprotein [LDL] cholesterol), but also hemorrheologic abnormalities could
      causally be involved in the atherosclerotic process. To elucidate potential
      effects of hemorrheological disturbances, we investigated patients suffering from
      primary hyperlipoproteinemias with both low (familial hypertriglyceridemia, n =
      25) and high (type III hyperlipoproteinemia, n = 21; familial
      hypercholesterolemia, n = 19; mixed hyperlipoproteinemia, n = 19) atherosclerotic
      risk, as well as healthy controls (n = 49) in a cross-sectional design.
      Dyslipoproteinemias were classified by lipoprotein measurements (using
      ultracentrifugation), family history, and apolipoprotein E phenotype.
      Hemorrheology was characterized by the measurement of fibrinogen concentration,
      viscosity of plasma and blood at different shear rates, and red cell aggregation
      (RCA) at stasis and low shear. Fibrinogen concentration was lower in controls
      (2.38 +/- 0.09 g/L) compared with familial hypercholesterolemia (3.19 +/- 0.19
      g/L), to type III hyperlipoproteinemia (3.02 +/- 0.12 g/L), to familial
      hypertriglyceridemia (2.95 +/- 0.21 g/L) and to mixed hyperlipoproteinemia (3.01
      +/- 0.12 g/L) (P < .05, respectively) without differences between
      dyslipoproteinemia groups. Plasma viscosity was higher in patients with type III
      hyperlipoproteinemia (1.42 +/- 0.03 mPas), with familial hypertriglyceridemia
      (1.47 +/- 0.04 mPas), and with mixed hyperlipoproteinemia (1.43 +/- 0.02 mPas)
      compared with controls (1.29 +/- 0.01 mPas) (P < .05, respectively). After
      including 6 lipoprotein parameters in a general linear model, plasma viscosity,
      blood viscosity, and RCA were higher in familial hypertriglyceridemia compared
      with healthy controls and familial hypercholesterolemia (P < .05, respectively).
      As most of the hemorrheologic abnormalities were still significant after
      adjusting for lipoprotein concentrations, they seem to be at least partly
      independent from direct lipoprotein effects. Hemorrheologic abnormalities in
      familial hypertriglyceridemia (low atherosclerotic risk) were at least as marked
      as in dyslipoproteinemias with high atherosclerotic risk, suggesting that it
      might be most important to determine lipoprotein concentrations and to define
      exactly the type of dyslipoproteinemia for estimating the individual
      cardiovascular risk in these patients.

PMID- 11229425
TI  - Differential effects of fasting and dehydration in the pathogenesis of diabetic
      ketoacidosis.
AB  - Glycemia varies widely in patients with diabetic ketoacidosis (DKA), with plasma
      glucose concentrations between 10 to 50 mmol/L commonly encountered. The
      mechanism of this glycemic variability is uncertain. Our study examined the
      differential effects of fasting and dehydration on hyperglycemia induced by
      withdrawal of insulin in type 1 diabetes. To evaluate the respective roles of
      dehydration and fasting in the pathogenesis of DKA, 25 subjects with type 1
      diabetes were studied during 5 hours of insulin withdrawal before (control) and
      after either 32 hours of fasting (n = 10) or dehydration of 4.1% +/- 2.0% of
      baseline body weight (n = 15). Samples were obtained every 30 minutes during
      insulin withdrawal for substrate and counterregulatory hormone levels and rates
      of glucose production and disposal. Fasting resulted in reduced plasma glucose
      concentrations compared with the control study, while dehydration resulted in
      increased plasma glucose concentrations compared with the control study (P <
      .001). Glucose production and disposal were decreased during the fasting study
      and increased during the dehydration study compared with the control study.
      Glucagon concentrations and rates of development of ketosis and metabolic
      acidosis were increased during both fasting and dehydration compared with
      control. These data suggest that fasting and dehydration have differential
      effects on glycemia during insulin deficiency, with dehydration favoring the
      development of hyperglycemia and fasting resulting in reduced glucose
      concentrations. This finding is probably attributable to the differing effect of
      these conditions on endogenous glucose production, as well as to differences in
      substrate availability and counterregulatory hormone concentrations. The severity
      of pre-existing fasting and dehydration likely explains much of the variability
      in plasma glucose concentrations observed in DKA.

PMID- 11229426
TI  - Differential effects of obesity with and without hyperinsulinemia on plasma
      lipoprotein(a) concentrations in men.
AB  - To determine the association of in vivo concentrations of insulin, obesity, and
      gender with lipoprotein(a) [Lp(a)] levels, we used a cross-sectional population
      based survey of a multistage random sample of the Mexico City adult population.
      We studied 423 normoglycemic, normotensive subjects from an original sample of
      825, comprised of 239 men and 189 women with a mean age of 38.6 years (range, 17
      to 90). All subjects were divided into 8 groups according to body mass index,
      fasting insulin, and gender. Lp(a) concentrations (mg/dL) were similar in obese
      women with and without high insulin levels (19.9 v 18.6), but hyperinsulinemic
      obese men had significantly lower Lp(a) levels than normoinsulinemic obese men
      (7.9 v 29.4). In addition, the proportion of obese men with Lp(a) concentrations
      of > or = 30 mg/dL was significantly higher in the normoinsulinemic than in the
      hyperinsulinemic (29.2% v 0.0%). The frequency distribution of Lp(a) levels was
      shifted to a lower range in hyperinsulinemic men compared with normoinsulinemic
      men. Our results show that in men, hyperinsulinemic obesity is associated with
      low Lp(a) levels, while obesity with normoinsulinemia is related to increased
      Lp(a) concentration. These observations were not found in women. These findings
      may explain the conflicting results reported by several studies.

PMID- 11229427
TI  - The beta3-adrenergic receptor Trp64Arg mutation is not associated with coronary
      artery disease.
AB  - There is some evidence that the Trp64Arg polymorphism of the beta3-adrenergic
      receptor (beta3-AR) is associated with atherogenic risk factors that include
      weight gain, insulin resistance, and diabetes. The objective of this cross
      sectional study was to investigate the relationship between the Trp64Arg
      polymorphism and coronary artery disease (CAD). A total of 1,000 consecutive
      patients with angiographically confirmed CAD and 1,000 controls, carefully
      matched for age and sex, were genotyped for the Trp64Arg polymorphism by
      polymerase chain restriction and subsequent restriction fragment length
      polymorphism analysis. Among cases with CAD, 83.3% were wild-type Trp/Trp, 15.8%
      were heterozygotes, and 0.9% were homozygous Arg/Arg compared with 82.3%, 17.3%,
      and 0.4%, respectively, among controls (P = .27). The odds ratios for the
      presence of Trp/Arg and Arg/Arg in cases and controls were 0.90 (95% confidence
      interval [CI] 0.7 to 1.2; P = .40) and 2.2 (95% CI 0.7 to 7.2; P = .17),
      respectively. There was no effect modification by gender and atherogenic risk
      factors, including diabetes, hypercholesterolemia, hypertension, and smoking.
      Furthermore, there was no evidence of an association with premature disease onset
      (< 40 years) or extent of disease. In conclusion, the results of this study in a
      large sample of clinically well-characterized patients indicate that neither the
      Trp/Arg nor the Arg/Arg genotype represents a major risk factor for
      angiographically confirmed coronary artery disease.

PMID- 11229428
TI  - Caval backflow: a potential problem during blood sampling from the hepatic vein.
AB  - A proper measurement of splanchnic metabolism involves sampling blood from the
      hepatic vein without backflow contamination of blood from the caval vein. We have
      investigated the potential problem of caval backflow in human volunteers with an
      indwelling hepatic vein catheter by sampling blood with different amounts of
      suction on the syringe (ie, sampling speeds). We also investigated the potential
      problem in pigs in which a balloon catheter was inserted in the hepatic vein.
      Pure hepatic vein samples were obtained with the balloon inflated and compared
      with samples obtained from the same catheter in the conventional manner. In
      overnight fasted humans, drawing blood samples from the hepatic vein with minimal
      suction ("slow" drawing) resulted in glucose values 9.6% higher than drawing the
      samples with greater suction ("fast" drawing). The calculated arterial-venous
      balance across the splanchnic bed was 4.8 times greater with "slow" blood drawing
      as compared with "fast" drawing. Values obtained from the pigs showed no
      concentration differences between pure hepatic vein samples and "slow" drawing
      from the hepatic vein. The current study indicates that it is possible to obtain
      a "true" hepatic vein sample, but backflow from the caval vein is a potential
      pitfall that can have a physiologically significant impact on calculated balance
      data.

PMID- 11229429
TI  - Contrasting effects of L-arginine on insulin-mediated blood flow and glucose
      disposal in the elderly.
AB  - Insulin increases skeletal muscle blood flow in healthy young subjects by a
      nitric oxide (NO)-dependent mechanism. Impairment of this mechanism may
      contribute to the insulin resistance of normal aging. We tested the hypothesis
      that L-arginine, the endogenous precursor for NO synthesis, would augment insulin
      mediated vasodilation and in so doing increase insulin-mediated glucose uptake
      (IMGU) in healthy elderly subjects. Experiments were conducted on healthy young
      (n = 9; age, 24 +/- 1 years; body mass index, 24 +/- 1 kg/m2) and old (n = 9;
      age, 77 +/- 2 years; BMI, 25 +/- 1 kg/m2) subjects. Each underwent two euglycemic
      clamp studies. On both occasions, insulin was infused from 0 to 120 minutes
      (young, 40 mU/m2/min; old, 34 mU/m2/min). On 1 day, insulin was continued and L
      arginine (7.5 mg/kg/min) was coinfused from 120 to 240 minutes. On the second
      study day, the insulin infusion from 120 minutes onward was adjusted in each
      subject to match corresponding plasma concentrations during the L-arginine
      infusion. Calf blood flow was measured bilaterally using venous occlusion
      plethysmography. Mean arterial blood pressure decreased in response to L-arginine
      in both young (77 +/- 1 v 73 +/- 1 mm Hg; P < .05) and old (103 +/- 2 v 94 +/- 2
      mm Hg; P < .01). Calf vascular conductance increased in young (from 0.094 +/-
      0.009 to 0.113 +/- 0.012 mL/100 mL/min/mm Hg; P < .01) and old (from 0.035 +/-
      0.003 to 0.050 +/- 0.003 mL/100 mL/min/mm Hg; P < .01), consistent with the
      concept that the addition of substrate can augment skeletal muscle endothelial NO
      production in both age groups. Calf blood flow increased in both young (control,
      7.04 +/- 0.73; L-arginine, 8.02 +/- 0.78 mL/100 mL/min; P < .05) and old
      (control, 3.60 +/- 0.27: L-arginine, 4.65 +/- 0.23 mL/100 mL/min; P < .0001)
      subjects, yet L-arginine had no impact on glucose disposal in either age group.
      In conclusion, L-arginine caused skeletal muscle vasodilation in the elderly,
      indicating that this endothelially mediated response is not attenuated with age.
      However, this increase in blood flow had no impact on insulin-mediated glucose
      uptake.

PMID- 11229430
TI  - Mitochondrial-encoded gene regulation in rat pancreatic islets.
AB  - Mitochondrial adenosine triphosphate (ATP) generation plays a major role in
      insulin secretion in pancreatic islet beta cells. The relationship between age
      and nutritional status of the islet and mitochondrial gene messenger RNA (mRNA)
      expression was investigated. Three animal groups were studied: infant (12-day
      old) rats fed either mother's milk or a high carbohydrate (HC) diet; young (2 to
      4-month-old) rats; and old (12 to 14-month-old) rats. The expression of
      mitochondrial cytochrome oxidase (CYO) (subunits I, II, and III), beta
      nicotinamide adenine dinucleotide, reduced form dehydrogenase subunit 4 (NADH
      DH4), and ATP synthase (subunit 6) (ATP-SYN6) mRNAs was characterized by
      semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR). The
      mitochondrial gene mRNAs were identified in each of the groups of rat islets and
      in RINm5F cells. CYO-II mRNA expression in young and old rat pancreatic islets
      was 12.7- and 8.2-fold higher, respectively, compared with the level in infant
      rat islets. The expression of NADH-DH4 and ATP-SYN6 mRNAs was 47% and 40% lower,
      respectively, in young rat islets compared with the level in infant rat islets.
      CYO-I, CYO-III, and cytoplasmic glyceraldehyde-3-phosphate dehydrogenase (GPDH)
      mRNA expression did not differ between experimental groups. Artificial rearing of
      infant rat pups on a HC diet for 8 days lead to a 3.3-fold increase in islet CYO
      II mRNA expression compared with mother-fed pups. However, glucose (11 mmol/L)
      stimulation of cultured isolated islets from young and old rats for 4 days failed
      to affect the expression level of mitochondrial gene mRNAs. Thus, aging affected
      the differential expression of CYO-II, NADH-DH4, and ATP-SYN6 mRNAs in rat
      islets. CYO-II mRNA expression was modulated only in infant rat islets after in
      vivo administration of carbohydrate.

PMID- 11229431
TI  - Low-density lipoprotein (LDL)-induced monocyte-endothelial cell adhesion, soluble
      cell adhesion molecules, and autoantibodies to oxidized-LDL in chronic renal
      failure patients on dialysis therapy.
AB  - Premature atherosclerosis is a major cause of morbidity and mortality in chronic
      renal failure patients undergoing dialysis. In this study, we compared
      autoantibodies to oxidized low-density lipoprotein (OX-LDL), soluble cell
      adhesion molecules (CAMs), and the effect of both LDL and OX-LDL on monocyte
      endothelial cell adhesion in chronic renal failure patients on hemodialysis (HD,
      n = 16) and peritoneal dialysis (PD, n = 17) compared with matched healthy
      control subjects (C, n = 17). In addition, we studied the effect of
      supplementation with RRR-alpha-tocopherol (AT) 800 IU/d for 12 weeks on the above
      measures. LDL and OX-LDL induced adhesion of U937 cells to cultured endothelium,
      soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intracellular
      adhesion molecule-1 (sICAM-1), and soluble E-selectin (sE-selectin);
      autoantibodies to OX-LDL and markers of lipid peroxidation were determined before
      and after AT supplementation. Native LDL from PD patients induced greater
      monocyte-endothelial cell adhesion than LDL from C subjects (43.8% +/- 17.0%
      v25.3% +/- 17.7%, respectively, P = .0028). OX-LDL from chronic renal failure
      patients on both PD and HD stimulated greater adhesion than OX-LDL from the C
      subjects (68.0% +/- 18.5% and 57.6% +/- 15.1% v 40.9% +/- 17.3%, respectively, P
      < .01); OX-LDL from PD patients induced greater adhesion than that from HD
      patients (P < .01). Plasma methylglyoxal levels were significantly increased in
      both HD and PD groups, with higher levels in the HD group. Chronic renal failure
      patients on HD and PD also had higher levels of plasma sVCAM-1 and sE-selectin
      than C subjects (P < .01), indicating endothelial activation. Titers of
      autoantibodies to OX-LDL were not elevated in renal failure patients.
      Supplementation with AT 800 IU/d for 12 weeks, while resulting in significant
      enrichment with AT in LDL, did not have a significant effect on any of the
      parameters studied. This study makes the novel observation that the LDL of
      chronic renal failure patients on HD and PD appears to be potentially more
      atherogenic, since it induces greater monocyte-endothelial cell adhesion.

PMID- 11229432
TI  - Long-term denervation impairs insulin receptor substrate-1-mediated insulin
      signaling in skeletal muscle.
AB  - Long-term denervation is associated with insulin resistance. To investigate the
      molecular bases of insulin resistance, the downstream signaling molecules of
      insulin receptor including insulin receptor substrate-1 (IRS-1) and
      phosphatidylinositol 3-kinase (PI 3-K) were examined in skeletal muscle of rats
      after 7 days of denervation. Long-term denervation attenuated insulin-stimulated
      activation of the initial steps of the intracellular signaling pathway. Insulin
      stimulated tyrosine phosphorylation of insulin receptor was reduced to 36% (P <
      .005), as was the phosphorylation of IRS-1 to 34% (P < .0001) of control. While
      insulin receptor protein level was unchanged, the protein expression of IRS-1 was
      significantly decreased in denervated muscles. Insulin-stimulated percent
      tyrosine phosphorylation of IRS-1, normalized to the IRS-1 protein expression,
      was also reduced to 55% (P < .01) of control in denervated muscle. Denervation
      caused a decline in the insulin-induced binding of p85 regulatory subunit of PI 3
      K to IRS-1 to 61% (P < .001) and IRS-1-associated PI 3-K activity to 57% (P <
      .01). These results provide evidence that long-term denervation results in
      insulin resistance because of derangements at multiple points, including tyrosine
      phosphorylation of insulin receptor and its downstream signaling molecule, IRS-1,
      protein expression of IRS-1, and activation of PI 3-K.

PMID- 11229433
TI  - Exaggerated pancreatic polypeptide secretion in Pima Indians: can an increased
      parasympathetic drive to the pancreas contribute to hyperinsulinemia, obesity,
      and diabetes in humans?
AB  - Vagally-mediated hyperinsulinemia is a common abnormality in various rodent
      models of genetic and hypothalamic obesity that have a high propensity for type 2
      diabetes. We hypothesized that Pima Indians, a population with a high prevalence
      of hyperinsulinemia, obesity, and type 2 diabetes also have an increased
      parasympathetic drive to the pancreas. To test this, we measured plasma
      concentrations of insulin and pancreatic polypeptide (PP), a surrogate marker of
      pancreatic vagal tone, in lean and obese Pima Indian and Caucasian children (n =
      43, 26P/17C, 7 +/- 1 y) and adults (n = 92, 61P/31C, 31 +/- 5 y). Pima Indian
      children had approximately 2-fold higher fasting insulin and 57% higher fasting
      PP concentrations than age- and sex-matched Caucasian children (P < .05).
      Although there was no difference in fasting PP concentration between Pima Indian
      and Caucasian adults, in response to a mixed meal, Pima Indians had a 51% higher
      early (30 minutes) PP concentration and 2-fold higher early insulin concentration
      than Caucasians (P < .05). PP concentrations at 60 minutes and 120 minutes after
      the meal were also markedly higher in both lean and obese Pima Indians compared
      with lean and obese Caucasians. These results suggest that Pima Indians may have
      an increased parasympathetic drive to the pancreas, which could lead to a primary
      hypersecretion of insulin and contribute to their high propensity for obesity and
      diabetes, as is the case in various rodent models of obesity.

PMID- 11229434
TI  - Inhibitory effect of rifampicin on the depressive action of interleukin-1 on
      cytochrome P-450-linked monooxygenase system.
AB  - It has been shown that interleukin 1 (IL-1) depresses cytochrome P-450-linked
      monooxygenases. In the present study, the effects of rifampicin on the depressive
      action of IL-1 on the activities and gene expression of xenobiotic metabolizing
      enzymes in liver microsomes were investigated in vivo using Wistar rats. Among
      the monooxygenases studied, we especially focused on the induction mechanism for
      CYP2D, known to be depressed by IL-1 and responsible for the oxidation of
      xenobiotics, debrisoquine, bufuralol, and sparteine. The CYP2D protein and its
      messenger RNA (mRNA) were quantitated by Western blot and slot blot hybridization
      analyses in the groups treated with and without rifampicin and IL-1. The results
      showed that the depressive action of IL-1 on CYP2D was offset by additional
      administration of rifampicin, and the P-450 (CYP2D-linked monooxygenase system is
      up-regulated at the mRNA level by rifampicin. These results show that rifampicin
      has a blocking effect on the depressive action of IL-1 on the CYP2D subfamily.

PMID- 11229435
TI  - Prolonged stability of endogenous cardiotrophin-1 in whole blood.
AB  - Cardiotrophin-1 (CT-1) is a recently identified cytokine of the interleukin-6 (IL
      6) family that signals through the gp130 signalling pathway. CT-1 may be of
      central importance to the pathogenesis of ventricular remodelling in patients
      with acute myocardial infarction (AMI) and therefore have clinical value in the
      identification of patients with impaired ventricular function. Central to the
      clinical use of CT-1 is in the in vitro stability of the peptide. Twelve subjects
      were recruited. A total of 25 mL of peripheral venous blood was collected into
      chilled polypropylene tubes containing EDTA and aprotinin and divided into 5
      aliquots. One sample was spun in a prerefrigerated centrifuge (4 degrees C) at
      3,000 rpm for 10 minutes and plasma separated and frozen at -70 degrees C
      immediately. Remaining samples were stored for 24 and 48 hours at room
      temperature or on ice. CT-1 in extracted plasma specimens was measured with a
      competitive chemiluminescent assay. The concentration of CT-1 in samples stored
      optimally was 43.1 +/- 6.05 fmol/mL. CT-1 levels for storage at room temperature
      compared with ice at the remaining time points were as follows: 24 hours, 41.5 +/
      5.76 v 37.5 +/- 8.66; and 48 hours, 42.6 +/- 6.28 v 41.0 +/- 5.42 fmol/mL. There
      were no significant changes in concentrations of CT-1 stored optimally or kept
      for up to 48 hours in aliquots of whole blood at room temperature or on ice. We
      conclude that CT-1 is stable in specimens of whole blood treated with EDTA and
      aprotinin and stored for up to 48 hours at room temperature or on ice, hence
      permitting its development in the routine clinical investigation of patients with
      heart failure.

PMID- 11229436
TI  - Effect of furosemide on renal excretion of oxypurinol and purine bases.
AB  - To examine whether furosemide affects the plasma concentration and urinary
      excretion of purine bases and oxypurinol, we administered allopurinol (300 mg)
      orally to 6 healthy subjects and then administered furosemide (20 mg)
      intravenously 10 hours later. Furosemide (20 mg) decreased the urinary excretion
      of uric acid by 40% (P < .01), oxypurinol by 39% (P < .05), and xanthine by 43%
      (P < .05) and the fractional clearance of uric acid by 45% (P < .01) and
      oxypurinol by 34% (P < .05) when measured 1 to 2 hours after administration.
      Moreover, furosemide increased the plasma concentration of uric acid by 6% at 1.5
      hours after administration. These results indicate that furosemide may decrease
      the urinary excretion of uric acid and oxypurinol by acting on their common renal
      transport pathway(s). In addition, it is suggested that the effect of furosemide
      on oxypurinol is clinically important, since the hypouricemic effect of
      allopurinol may become more potent as a result.

PMID- 11229437
TI  - Interactions among the glucocorticoid receptor, lipoprotein lipase, and
      adrenergic receptor genes and plasma insulin and lipid levels in the Quebec
      Family Study.
AB  - The aim of the study was to investigate the possible interactions among the
      glucocorticoid receptor (GRL), lipoprotein lipase (LPL), and adrenergic receptor
      (ADR) genes on plasma insulin and lipid levels. The study was cross-sectional and
      based on 742 individuals from phase 2 of the Quebec Family Study (QFS) cohort.
      Gene markers were identified by Southern blot analysis or polymerase chain
      reaction (PCR). Plasma glucose and insulin in the fasted state and during an oral
      glucose tolerance test (OGTT) were determined and insulin and glucose areas were
      computed. Triglyceride (TG) and cholesterol concentrations in plasma and
      lipoprotein fractions were determined enzymatically. The results show that GRL
      and LPL variants had independent effects on plasma high-density lipoprotein
      cholesterol (HDL-C) and two beta2-ADR variants were related to total cholesterol
      concentrations. The alpha2-ADR gene Dral polymorphism was the only variant that
      had an independent effect on the plasma insulin area. Gene-gene interaction
      effects were found between GRL and alpha2-ADR genes for low-density lipoprotein
      cholesterol ([LDL-C] P = .013) and between GRL and LPL genes for HDL-C (P =
      .045). Higher-order interaction effects involving GRL, LPL, and ADR markers were
      observed for the plasma insulin area (P = .001 to .025) but not the glucose area.
      After correction for multiple tests, the findings remained essentially unchanged
      for the insulin area but became nonsignificant for the lipid phenotypes. In
      conclusion, multiple interactions among GRL, LPL, and ADR gene markers contribute
      to insulin metabolism and perhaps to lipid levels, while no significant effect is
      found for each gene separately. The LPL locus appears to determine the pattern of
      interactions with ADR and GRL loci. These results suggest that gene-gene
      interaction effects could play a role in the etiology of risk factors for common
      chronic diseases.

PMID- 11229438
TI  - Systemic prostaglandin E1 infusion and hepatic aminonitrogen to urea nitrogen
      conversion in patients with type 2 diabetes in poor metabolic control.
AB  - Amino acid catabolism and urea synthesis are increased in type 2 diabetes
      mellitus in poor metabolic control. In different catabolic conditions,
      prostaglandins (PGs) of the E series produced metabolic effects on nitrogen
      metabolism, decreasing urea formation. In 10 patients with type 2 diabetes in
      poor metabolic control, urea synthesis and amino acid to urea nitrogen exchange
      were measured in the basal state and during an alanine load (6 hours) with 2-hour
      superinfusion of a PGE1 analog (30 microg/h) or saline in random order. The urea
      synthesis rate was calculated as the sum of urinary urea excretion and urea
      accumulation in total body water (TBW); total nitrogen exchange was calculated as
      the difference between infused amino acid-nitrogen and urea appearance. Plasma
      alpha-aminonitrogen (alpha-amino-N) increased 100% in response to alanine, to a
      steady-state without differences in relation to PG superinfusion. The urea
      synthesis rate (mean +/- SD) was 34.0 +/- 11.4 mmol/h in the basal period and
      increased to 161.2 +/- 37.0 during alanine + saline and to 113.5 +/- 34.6 during
      alanine + PG (P < .001). Nitrogen exchange was negative at baseline (-25.0 +/-
      9.0 mmol/h). It became moderately positive during alanine + saline (14.6 +/-
      25.1) and far more positive during alanine + PG (53.5 +/- 21.4), with the
      difference due to reduced urea formation. The metabolic effects of PG were not
      related to differences in insulin and glucagon. We conclude that PGE1 slows the
      high rate of hepatic urea-N synthesis in poorly controlled type 2 diabetes. Such
      metabolic effects have therapeutic implications.

PMID- 11229439
TI  - 4-Hydroxynonenal as a biological signal: molecular basis and pathophysiological
      implications.
AB  - Reactive oxygen intermediates (ROI) and other pro-oxidant agents are known to
      elicit, in vivo and in vitro, oxidative decomposition of omega-3 and omega-6
      polyunsaturated fatty acids of membrane phospholipids (i.e, lipid peroxidation).
      This leads to the formation of a complex mixture of aldehydic end-products,
      including malonyldialdehyde (MDA), 4-hydroxy-2,3-nonenal (HNE), and other 4
      hydroxy-2,3-alkenals (HAKs) of different chain length. These aldehydic molecules
      have been considered originally as ultimate mediators of toxic effects elicited
      by oxidative stress occurring in biological material. Experimental and clinical
      evidence coming from different laboratories now suggests that HNE and HAKs can
      also act as bioactive molecules in either physiological and pathological
      conditions. These aldehydic compounds can affect and modulate, at very low and
      nontoxic concentrations, several cell functions, including signal transduction,
      gene expression, cell proliferation, and, more generally, the response of the
      target cell(s). In this review article, we would like to offer an up-to-date
      review on this particular aspect of oxidative stress--dependent modulation of
      cellular functions-as well as to offer comments on the related pathophysiological
      implications, with special reference to human conditions of disease.

PMID- 11229440
TI  - Regulation of tumor necrosis factor-induced, mitochondria- and reactive oxygen
      species-dependent cell death by the electron flux through the electron transport
      chain complex I.
AB  - Tumor necrosis factor (TNF) induces a caspase-independent but mitochondria
      dependent cell death process in the mouse fibrosarcoma cell line L929.
      Mitochondria actively participate in this TNF-induced necrotic cell death by the
      generation of mitochondrial reactive oxygen species (ROS). The aim of this study
      was to identify the mitochondrial components involved in TNF-induced production
      of ROS and their regulation by bioenergetic pathways. Therefore, we analyzed the
      bioenergetic characteristics in two metabolic L929 variants that exhibit
      different sensitivities to TNF. L929gln cells use glutamine as respiratory
      substrate and are far more susceptible to TNF-induced ROS generation and cell
      death as L929glc cells that use glucose as respiratory substrate. We show that
      the higher levels of reducing NAD(P)H equivalents, detected in the desensitized
      L929glc cells, do not cause diminished ROS generation. To the contrary, TNF
      increases the levels of NAD(P)H, probably altering complex I activity. A
      multiparameter analysis of electron flux through the mitochondrial electron
      transport chain, TNF-induced ROS levels, and cell death convincingly demonstrates
      a dependence of TNF signaling on complex I activity. Also, the sensitizing effect
      of glutamine metabolism correlates with an enhanced contribution of complex I to
      the overall electron flux. This participation of complex I activity in TNF
      induced cell death is regulated by substrate availability rather than by a direct
      modification of complex I proteins. From the results presented in this paper we
      conclude that TNF-induced ROS generation and cell death are strongly regulated by
      bioenergetic pathways that define electron flux through complex I of the electron
      transport chain.

PMID- 11229441
TI  - Heat shock and 5-azacytidine inhibit nitric oxide synthesis and tumor necrosis
      factor-alpha secretion in activated macrophages.
AB  - To elucidate the role of stress response during macrophage activation, the
      effects of heat shock and the amino acid analog, 5-azacytidine on nitric oxide
      (NO) production, tumor necrosis factor-alpha (TNF-alpha) secretion, and heat
      shock protein (HSP) synthesis have been studied in murine peritoneal macrophages
      (C57BL/6). Heat shock (1 hr at 43 degrees C) or 5-azacytidine markedly inhibited
      the release of NO into the medium from interferon-gamma (IFN-gamma) plus
      lipopolysaccharide (LPS)-stimulated macrophages. Although heat shock
      significantly decreased TNF-alpha secretion only at the initiation stage of
      macrophage stimulation, 5-azacytidine treatment resulted in a more prolonged
      reduction in the secretion of TNF-alpha. When heat-shocked cells were stimulated
      with IFN-gamma plus LPS under normal culture conditions at 37 degrees C, the heat
      shock-induced inhibition of NO release reversed progressively with increasing
      recovery time. Although the total amount of cellular HSP72 measured by Western
      blot increased time-dependently over 7 hr, newly synthesized HSP72 measured by
      [35S]methionine incorporation was evident only after 1 and 3 hr of recovery time
      after heat shock treatment. At these time points, the lowest nitrite accumulation
      and TNF-alpha secretion into the medium was evident. It is concluded that
      signaling pathways related to newly synthesized HSP such as HSP72 are implicated
      in the down regulation of NO synthesis and TNF-alpha secretion in macrophages.

PMID- 11229442
TI  - Beta-cells, oxidative stress, lysosomal stability, and apoptotic/necrotic cell
      death.
AB  - Reactive oxygen intermediates (ROI) may be involved in the destruction of
      pancreatic beta-cells during the development of insulin-dependent diabetes
      mellitus (IDDM). To investigate the possible role of lysosomes in this process,
      normal mouse beta-cells were cultured as monolayers at D-glucose concentrations
      of 1.6 (pronounced crinophagy), 11 or 28 mM (minimal crinophagy), subjected to a
      low level of oxidative stress and returned to standard culture conditions. Some
      cultures were exposed to desferrioxamine (Des) before the oxidative stress. As a
      result of such stress, many of the cells' lysosomes ruptured with consequent
      apoptosis or necrosis. Cells kept at 1.6 mM glucose were rich in secretory
      granules, showed crinophagy/autophagy, were very sensitive to oxidative stress,
      and had the least stable lysosomes. Cells kept at 28 mM glucose did not show
      crinophagy, contained fewer secretory granules, were less sensitive to oxidative
      stress, and had more stable lysosomes. Des-treated cells behaved almost as cells
      not exposed to oxidative stress at all. The findings suggest that iron may occur
      together with zinc within the secretory granules and that it sensitizes
      crinophagic lysosomes to oxidative stress. The stress that was applied in this
      study may be comparable to what occurs within the vicinity of activated
      macrophages during autoimmune insulitis.

PMID- 11229443
TI  - Redox regulation of NF-kappaB and AP-1 in ischemic reperfused heart.
AB  - Two redox-sensitive transcription factors, AP-1 and NF-kappaB, have been
      implicated in the regulation of apoptosis induced by myocardial ischemia and
      reperfusion. Hearts adapted to ischemic stress by cyclic episodes of short
      durations of ischemia and reperfusion attenuate apoptotic cell death. This study
      was designed to examine the pattern of expression of these transcription factors
      and the redox sensitive transacting molecule, AP-1, NF-kappaB, and- Bcl-2, during
      ischemia/ reperfusion and myocardial adaptation to ischemia. NF-kappaB binding
      activity was low in nonischemic control heart. Fifteen minutes of ischemia
      resulted in translocation of NF-kappaB from cytosol to nucleus followed by
      activation. The binding activity of NF-kappaB was further enhanced after 60 min
      of ischemia. An even higher degree of NF-kappaB binding was noticed in the
      ischemically adapted myocardium. In contrast, AP-1 binding activity was highest
      for the hearts subjected to 15 min of ischemia followed by 2 hr of reperfusion.
      AP-1 binding was higher in the ischemically adapted heart as compared to the
      control. The Bcl-2 gene, which was found to be present in the control hearts, had
      lowered expression after 15 min of ischemia and 2 hr of reperfusion. Significant
      upregulation of Bcl-2 mRNA was noticed in the ischemically adapted hearts.
      Apoptotic cardiomyocytes were found only in the hearts that were reperfused for
      at least 90 min. No apoptosis occurred in hearts subjected up to 1 hr of ischemia
      or ischemic adaptation. Prolonged reperfusion, and not ischemia up to 1 hr, can
      induce cardiomyocyte apoptosis. In concert, ischemic/reperfusion increases the
      nuclear binding of both AP-1 and NF-kappaB, but downregulates Bcl-2 gene.
      Ischemic adaptation attenuates apoptotic cell death, further increases NF-kappaB
      binding activity and Bcl-2 gene induction, but reduces AP-1 binding activity.
      These results suggest that AP-1, NF-kappaB, and Bcl-2 are differentially
      regulated by ischemia/reperfusion and ischemic adaptation.

PMID- 11229445
TI  - Oxidation-dependent changes in the stability and permeability of lipid bilayers.
AB  - Peroxidation-dependent change in the permeability of lipid bilayers was mesaured
      by using artificial membrane systems, that is, planar lipid bilayers and
      liposomes. The unsaturated fatty acyl chains of phospholipids in small
      unilamellar vesicles were peroxidized time-dependently by the hydroxyl radical
      chemically generated by the reaction of H2O2 and Cu(en)2. In contrast, at the
      same hydroxyl radical concentration and time ranges, no ionic current through the
      planar lipid bilayers and no release of K+ from the liposomes were observed.
      These findings indicate that accumulation of lipid peroxide within lipid bilayers
      is not responsible for the permeability increase that is often observed in
      biomembranes exposed to oxidative stresses. Higher concentration of the hydroxyl
      radical caused break-down of the planar lipid bilayers composed of the mixture
      (7:3) of phosphatidylethanolamine (PE) and phosphatidylcholine (PC). The bilayer
      containing 100% PE at least at one leaflet of the bilayer (facing the hydroxyl
      radical-generating solution) was not broken-down by the application of the
      hydroxyl radical, suggesting that PE stabilizes the planar lipid bilayer against
      the attack of the hydroxyl radical.

PMID- 11229444
TI  - Low-density lipoprotein oxidation and its prevention by amidothionophosphate
      antioxidants.
AB  - Amidothionophosphates (AMTPs) are a novel group of antioxidants that are lacking
      in pro-oxidant activity. In this paper, we compare two different
      amidothionophosphates: 2-hydroxy-ethyl amido, diethyl thionophosphate (AMTP-B),
      which contains a single primary amido group, and N,N',N
      tripropylamidothionophosphate (AMTP-3A), which contains three primary amido
      groups. The lipoprotein/medium partition coefficients of AMTP-3A and AMTP-B are
      74 and 38, respectively. Both protected isolated human low density lipoprotein
      (LDL) against oxidative damage induced by copper sulfate. Oxidative damage to
      polyunsaturated acyl chains was determined by gas chromatography (GC), and
      oxidation kinetics were monitored by following the accumulation of conjugated
      dienes spectrophotometrically at 234 nm. The AMTP antioxidants significantly
      protected the LDL against Cu2+-induced oxidation. However, if the LDLs were
      already partially oxidized, protection against oxidation by the AMTPs was
      reduced. AMTP-3A was more effective in protecting LDL than was AMTP-B. The
      difference in antioxidant activity was attributed to the 15-fold higher
      reactivity of AMTP-3A toward peroxides. Oxidizability of plasma lipoproteins from
      guinea pigs injected with AMTPs was strongly reduced.

PMID- 11229447
TI  - Homocysteine induces DNA synthesis and proliferation of vascular smooth muscle
      cells by a hydrogen peroxide-independent mechanism.
AB  - Elevated plasma levels of homocysteine have been identified as an important and
      independent risk factor for cerebral, coronary, and peripheral atherosclerosis,
      although the mechanisms are unclear. Homocysteine has been shown to promote cell
      proliferation and induction of the gene transcription factor c-fos in vascular
      smooth muscle cells. Earlier reports have suggested that homocysteine exert its
      effect via hydrogen peroxide (H2O2) produced during its metabolism. To evaluate
      the contribution of homocysteine to the pathogenesis of vascular diseases, we
      examined whether the effect of homocysteine on vascular smooth muscle cell growth
      is mediated by H2O2. We observed that 1.0 mM homocysteine induces DNA synthesis
      by 1.5-fold and proliferation of vascular smooth muscle cells two-fold in the
      presence of peroxide scavenging enzyme, catalase (2,600 U/ml). Our results
      suggest that homocysteine induces smooth muscle cell growth by an H2O2
      independent pathway and that the effects of homocysteine may sum together with
      the known initiating events produced by oxidative stress and accelerate the
      progression of atherosclerosis.

PMID- 11229446
TI  - Bifunctional anti/prooxidant potential of metallothionenin: redox signaling of
      copper binding and release.
AB  - Metallothioneins (MTs) are cysteine-rich metal-binding proteins that exert
      cytoprotection during metal exposure and oxidative stress. The roles of MT in
      copper (Cu) binding and release and modulation of redox cycling are unresolved.
      We hypothesized that Cu-binding to MT renders Cu redox inactive, but that
      oxidation of free thiols critical for metal binding can reduce MT/Cu interactions
      and potentiate Cu redox cycling. Overexpression of MT in cells by cadmium
      pretreatment or ectopic overexpression by gene transfer confers protection from
      Cu-dependent lipid oxidation and cytotoxicity. Using a chemically defined model
      system (Cu/ascorbate/H2O2) to study Cu/MT interactions, we observed that MT
      inhibited Cu-dependent oxidation of luminol. In the absence of H2O2, MT blocked
      Cu-dependent ascorbyl radical production with a stoichiometry corresponding to
      Cu/MT ratios < or = 12. In the presence of H2O2, Cu-dependent hydroxyl radical
      formation was inhibited only up to Cu/MT ratios < or = 6. Using low-temperature
      EPR of free Cu2+ to assess Cu/MT physical interactions, we observed that the
      maximal amount of Cu1+ bound to MT corresponded to 12 molar equivalents of Cu/MT
      with Cu and ascorbate alone and was reduced in the presence of H2O2. 2,2'
      Dithiodipyridine titration of MT SH-groups revealed a 50% decrease after H2O2,
      which could be regenerated by dihydrolipoic acid (DHLA). DHLA regeneration of
      thiols in MT was accompanied by restoration of MT's ability to inhibit Cu
      dependent oxidation of ascorbate. Thus, optimum ability of MT to inhibit Cu-redox
      cycling directly correlates with its ability to bind Cu. Some of this Cu,
      however, appears releasable following oxidation of the thiolate metal-binding
      clusters. We speculate that redox-dependent release of Cu from MT serves both as
      a mechanism for physiological delivery of Cu to specific target proteins, as well
      as potentiation of cellular damage during oxidative stress.

PMID- 11229448
TI  - The thermodynamics of xanthine oxidoreductase catalysis.
AB  - Xanthine oxidoreductase is a complex enzyme found in a wide range of organisms.
      Recent interest in this enzyme stems from its ability to produce reactive oxygen
      species under a range of conditions. It is found as a homodimer, each unit
      containing a molybdopterin cofactor, two iron sulfur centers, and FAD. The enzyme
      can exist in two forms that differ primarily in their oxidizing substrate
      specificity. The dehydrogenase form preferentially utilizes NAD+ as an electron
      acceptor but is able to donate electrons to molecular oxygen. Xanthine
      dehydrogenase from mammalian sources can be converted to an oxidase form that
      readily donates electrons to molecular oxygen, but does not reduce NAD+. The
      catalytic mechanism of both forms of the enzyme can be described in terms of a
      rapid equilibrium model in which reducing equivalents are distributed rapidly
      between the different redox centers of the enzyme on the basis of their midpoint
      potentials. The present commentary gives a brief overview of the literature
      concerning the rapid equilibrium model and the differences between the two enzyme
      forms. NADH is also discussed in terms of an alternative to xanthine or
      hypoxanthine as an electron donor.

PMID- 11229450
TI  - The effects of antidepressants on sexual functioning in depressed patients: a
      review.
AB  - Sexual dysfunction has long been noted as both a symptom of depressive illness
      and as a side effect of many of the medications used to treat depression.
      Although most people suffering from a major depressive illness would like to be
      sexually active, half experience a decrease in desire or sexual performance.
      Antidepressant medications often interfere with several parts of the sexual
      response. This review compares data from different types of research into the
      effect of antidepressant medications on the sexual response: case reports, chart
      reviews, and single- and double-blind studies with and without active control
      medications. From this review, it is clear that antidepressants of most classes
      interfere with human sexual functioning, with the notable exceptions of bupropion
      and nefazodone.

PMID- 11229449
TI  - Incidence of sexual dysfunction associated with antidepressant agents: a
      prospective multicenter study of 1022 outpatients. Spanish Working Group for the
      Study of Psychotropic-Related Sexual Dysfunction.
AB  - BACKGROUND: Antidepressants, especially selective serotonin reuptake inhibitors
      (SSRIs), venlafaxine, and clomipramine, are frequently associated with sexual
      dysfunction. Other antidepressants (nefazodone, mirtazapine, bupropion,
      amineptine, and moclobemide) with different mechanisms of action seem to have
      fewer sexual side effects. The incidence of sexual dysfunction is underestimated,
      and the use of a specific questionnaire is needed. METHOD: The authors analyzed
      the incidence of antidepressant-related sexual dysfunction in a multicenter,
      prospective, open-label study carried out by the Spanish Working Group for the
      Study of Psychotropic-Related Sexual Dysfunction. The group collected data from
      April 1995 to February 2000 on patients with previously normal sexual function
      who were being treated with antidepressants alone or antidepressants plus
      benzodiazepines. One thousand twenty-two outpatients (610 women, 412 men; mean
      age = 39.8 +/- 11.3 years) were interviewed using the Psychotropic-Related Sexual
      Dysfunction Questionnaire, which includes questions about libido, orgasm,
      ejaculation, erectile function, and general sexual satisfaction. RESULTS: The
      overall incidence of sexual dysfunction was 59.1% (604/1022) when all
      antidepressants were considered as a whole. There were relevant differences when
      the incidence of any type of sexual dysfunction was compared among different
      drugs: fluoxetine, 57.7% (161/279); sertraline, 62.9% (100/159); fluvoxamine,
      62.3% (48/77); paroxetine, 70.7% (147/208); citalopram, 72.7% (48/66);
      venlafaxine, 67.3% (37/55); mirtazapine, 24.4% (12/49); nefazodone, 8% (4/50);
      amineptine, 6.9% (2/29); and moclobemide, 3.9% (1/26). Men had a higher frequency
      of sexual dysfunction (62.4%) than women (56.9%), although women had higher
      severity. About 40% of patients showed low tolerance of their sexual dysfunction.
      CONCLUSION: The incidence of sexual dysfunction with SSRIs and venlafaxine is
      high, ranging from 58% to 73%, as compared with serotonin-2 (5-HT2) blockers
      (nefazodone and mirtazapine), moclobemide, and amineptine.

PMID- 11229451
TI  - Strategies for the treatment of antidepressant-related sexual dysfunction.
AB  - Sexual dysfunction and dissatisfaction are common symptoms associated with
      depression. Optimal antidepressant treatment should result in remission of the
      symptoms of the underlying illness and minimize the potential for short- and long
      term adverse effects, including sexual dysfunction. Sexual dysfunction and
      dissatisfaction are frequently persistent or worsen with the use of some
      antidepressant medications; this sexual dysfunction and dissatisfaction can have
      negative impact on adherence to treatment, quality of life, and the possibility
      of relapse. Successful management of sexual complaints during antidepressant
      treatment should begin with a systematic approach to determine the type of sexual
      dysfunction, potential contributing factors, and finally management strategies
      that should be tailored to the individual patient. The basic physiologic
      mechanisms of the normal sexual phases of libido, arousal, and orgasm and how
      these mechanisms may be interrupted by some antidepressants provide a framework
      for the clinician to utilize in order to minimize sexual complaints when
      initiating and continuing antidepressant treatment. This article provides
      guidelines, based upon this type of model, for the assessment, management, and
      prevention of sexual side effects associated with antidepressant treatment.

PMID- 11229452
TI  - Recognition and assessment of sexual dysfunction associated with depression.
AB  - Recognition of sexual dysfunction associated with depression or its treatment is
      critical for patient satisfaction and medication compliance. This report reviews
      relevant literature related to types of sexual problems, the etiology of sexual
      dysfunction, prevalence rates, barriers to assessment, and available instruments
      for evaluating sexual functioning in individuals with depression. Evaluation of
      sexual functioning should include examination of each phase of the sexual
      response cycle, with classification of sexual disorders as described in the DSM
      IV. Sexual functioning requires both an adequate hormonal milieu and appropriate
      neurotransmitter functioning. Evaluation of sexual functioning should include a
      sexual history, current level of sexual functioning, history and current
      diagnoses of medical and psychiatric illnesses, evaluation of medications and/or
      other substances taken, indicated endocrine measures, and targeted physical
      examination. Appropriate evaluation of sexual functioning associated with
      depression could help reduce the enormous societal costs of this disorder.

PMID- 11229453
TI  - ACR (American College of Rheumatology) Presidential Address: the future is now.

PMID- 11229454
TI  - The role of osteoprotegerin and receptor activator of nuclear factor kappaB
      ligand in the pathogenesis and treatment of rheumatoid arthritis.

PMID- 11229455
TI  - Involvement of ErbB-2 in rheumatoid synovial cell growth.
AB  - OBJECTIVE: The synovial tissue affected by rheumatoid arthritis (RA) is
      characterized by hyperproliferation of synovial cells. High amounts of epidermal
      growth factor (EGF) in the synovial fluid of RA patients contribute to the growth
      of rheumatoid synovial cells. To characterize the receptor for EGF in rheumatoid
      synovial cells, the expression and function of ErbB family members were examined.
      METHODS: Synovial tissues were obtained from surgical excisions. The expression
      of ErbB products was examined by immunohistochemistry and immunoblotting by using
      specific antibodies. Primary cultures were established from the surgical
      materials. Cell growth was measured using MTT. The levels and phosphorylation
      state of the ErbB-2 protein were analyzed by immunoprecipitation and
      immunoblotting. RESULTS: The expression of ErbB-2, but not other ErbB-related
      products, was detected in synovium with RA as compared with that with
      osteoarthritis (OA) and ligament injury. Growth of primary synovial cells with RA
      was inhibited by genistein, a tyrosine kinase inhibitor, and herceptin, a
      specific monoclonal antibody against ErbB-2. Herceptin showed a small effect on
      growth of primary synovial cells with OA. EGF stimulated the phosphorylation of
      ErbB-2 in primary synovial cells with RA. This EGF-stimulated phosphorylation was
      completely abrogated by genistein and herceptin. CONCLUSION: ErbB-2 is expressed
      in rheumatoid synovial cells and may function as the receptor for EGF. Our data
      suggest that mitotic signals from EGF family members are transduced by ErbB-2 in
      these cells. Inhibition of ErbB-2 may provide a new approach to the effective
      treatment for RA.

PMID- 11229456
TI  - Overexpression of transcription factor Ets-1 in rheumatoid arthritis synovial
      membrane: regulation of expression and activation by interleukin-1 and tumor
      necrosis factor alpha.
AB  - OBJECTIVE: To investigate the expression of the transcription factor Ets-1 in
      synovial tissue and cultured synovial fibroblasts from patients with rheumatoid
      arthritis (RA) and osteoarthritis (OA) and to study the regulation of Ets-1
      expression and activation in synovial fibroblasts by proinflammatory cytokines.
      METHODS: In situ expression of Ets-1 in synovial tissue from RA and OA patients
      was examined by double immunohistochemistry. The effects of interleukin-1 (IL-1)
      or tumor necrosis factor alpha (TNFalpha) on Ets-1 expression and activation (DNA
      binding) in cultured synovial fibroblasts were analyzed by Western blotting and
      DNA gel shift assay, respectively. In addition, the intracellular location of Ets
      1 in synovial fibroblasts was determined by immunofluorescence. RESULTS:
      Pronounced expression of Ets-1 was detected in synovial tissues from all RA
      patients evaluated, particularly in the synovial lining layer and the sublining
      areas. Ets-1 was expressed by both fibroblasts and macrophages as well as by
      endothelial cells, while only a few T cells stained positive for Ets-1. In
      synovial specimens from OA patients, Ets-1 expression was much less frequently
      observed and was largely restricted to vascular cells. Ets-1 was expressed to a
      similar degree in cultured synovial fibroblasts from RA and OA patients, as
      demonstrated by reverse transcriptase-polymerase chain reaction and Western
      blotting. Both IL-1 and TNFalpha induced pronounced up-regulation of Ets-1 in
      synovial fibroblasts. Moreover, binding of Ets-1 to its specific DNA binding site
      was induced by both cytokines, although with different time courses.
      Immunofluorescence staining revealed a dominant nuclear localization of Ets-1 in
      IL-1- or TNFalpha-stimulated synovial fibroblasts. CONCLUSION: The overexpression
      of Ets-1 observed in RA synovial tissue appears to be caused by TNFalpha and IL
      1, suggesting that Ets-1 may be an important factor in the cytokine-mediated
      inflammatory and destructive cascade characteristic of RA.

PMID- 11229457
TI  - Interferon-gamma-inducing activity of interleukin-18 in the joint with rheumatoid
      arthritis.
AB  - OBJECTIVE: To examine the levels of interleukin-18 (IL-18) bioactivity within the
      rheumatoid arthritis (RA) joint, and the differential effects of IL-12 and IL-18
      on interferon-gamma (IFNgamma) production by T cell infiltrates. METHODS:
      Expression of IL-18 protein and messenger RNA (mRNA) was determined by enzyme
      linked immunosorbent assay and reverse transcriptase-polymerase chain reaction,
      respectively. The biologic activity of IL-18 was detected on the basis of
      IFNgamma secretion from IL-18-responding human myelomonocytic KG-1 cells. To
      determine the extent of inhibitory activity on binding of IL-18 to its receptor,
      a [125I]-IL-18 binding inhibition assay was performed, using a Chinese hamster
      ovary cell line transfected with a murine IL-18 receptor. RESULTS: The amount of
      IL-18 protein detected in both the serum and synovial fluid of RA patients was
      markedly larger than that detected in the serum and synovial fluid
      ofosteoarthritis (OA) patients, and serum IL-18 levels correlated with the levels
      of serum C-reactive protein. IFNgamma production by KG-1 cells was more strongly
      stimulated in synovial fluid samples from RA patients than in samples from OA
      patients, and this activity was largely diminished in the presence of anti-IL-18
      antibody. In contrast, the activity of IL-18 binding inhibition in the serum and
      synovial fluid of RA patients was not significantly elevated compared with that
      in OA patients. RA synovial tissues showed increased expression of IL-18 mRNA and
      increased IL-18 protein synthesis compared with that in OA tissues. Purified
      CD14+ macrophages, but not activated fibroblast cell lines, from RA synovium were
      able to release mature IL-18, although both cell types expressed its transcripts.
      IL-18 alone showed a negligible effect on IFNgamma production by RA synovial
      tissue cells, in contrast to IL-12, which was directly stimulatory. However, IL
      12-induced IFNgamma production was synergistically enhanced by IL-18, and yet was
      >50% reduced by neutralization of endogenous IL-18 with anti-IL-18 antibody.
      CONCLUSION: These results indicate that IL-18, produced predominantly by tissue
      macrophages, primarily potentiates IL-12-induced IFNgamma production by T cell
      infiltrates in RA synovium. Detection of significant IL-18 bioactivity in the
      joints, despite the presence of IL-18 binding inhibitors, supports an integral
      role of this cytokine in perpetuating the IFNgamma-dominant T cell cytokine
      response in RA.

PMID- 11229458
TI  - Tumor necrosis factor markers show sex-influenced association with rheumatoid
      arthritis.
AB  - OBJECTIVE: The observation that not all shared-epitope genotypes confer the same
      risk suggests that a second HLA-region locus may confer risk. Tumor necrosis
      factor alpha (TNFgamma) is a possible candidate. We examined TNFalpha for sex
      influences on HLA-associated risk for rheumatoid arthritis (RA). METHODS: DRB1
      and TNF microsatellite typing of 297 Caucasian RA patients (132 men, 165 women)
      and 267 Caucasian controls was performed. RESULTS: The TNFab microsatellite
      haplotype distribution differed among the male RA, female RA, and control groups
      (P < 0.01); the difference was largely an excess of TNFa2b1 haplotypes in the
      male RA group. However, this did not simply reflect an excess of shared-epitope
      haplotypes bearing TNFa2b1. In RA, not all shared-epitope-bearing haplotypes had
      the same TNFab. The *0401-bearing haplotypes commonly had TNFa6b5, TNFa2b1,
      TNFa10b4, and TNFa11b4, while the *0404-bearing haplotypes had TNFa11b4. In the
      female RA group, TNFa2b1 was most often on *0401-bearing haplotypes. In the male
      RA group, there was a surprise: TNFa2b1 was often on HLA haplotypes without
      shared-epitope DRB1 alleles. To estimate the relative strength of associated HLA
      markers, we performed logistic regression analyses stratified by sex and
      controlling for a potential confounder, age at disease onset. Among women,
      TNFa2b3 favored RA (odds ratio 1.932, P < 0.05) while TNFa6b5 was protective
      (odds ratio 0.522, P < 0.05). Among males, TNFa2b1 and TNFa11b4 conferred
      elevated odds ratios (2.58 and 1.681, respectively, P < 0.05). However, the odds
      ratios for TNFa2b1 in men and TNFa2b3 in women were generally well below those
      for RA-associated DRB1 markers (for example, DRB1*0401 3.553 in male RA patients
      and 6.991 in female RA patients). CONCLUSION: Certain TNFab-bearing HLA
      haplotypes modify RA risk in a manner influenced by sex but independent of DRB1,
      particularly TNFa2b1 in men.

PMID- 11229459
TI  - Recognition of cell surface GD3 by monoclonal antibody anti-6C2 in rheumatoid
      arthritis synovial fluid: expression on human T cells with transendothelial
      migratory activity.
AB  - OBJECTIVE: We have previously reported that the anti-6C2 monoclonal antibody
      (mAb) defines a subset of human CD4+ memory T cells. The present study sought to
      determine the nature of the 6C2 molecule and the function associated with 6C2+ T
      cells, and to examine whether this T cell subset is involved in the
      pathophysiology of rheumatoid arthritis (RA). METHODS: Cytofluorographic analysis
      was performed for identification of T cell surface molecules displaying a
      distribution similar to that of the 6C2 molecule. T cells in the synovial fluid
      of RA patients were examined for expression of the 6C2 molecule. Transendothelial
      migratory activity was assessed by assay using monolayers of human endothelial
      cells. Specific reactivity of the anti-6C2 mAb was determined by immunoblotting
      on gangliosides separated by thin-layer chromatography, and flow cytometric
      analysis of the cells transfected with complementary DNA (cDNA) was performed for
      determination of the glycosyltransferases involved in biosynthesis of the
      gangliosides. RESULTS: On human peripheral T cells, the 6C2 molecule was
      distributed, by and large, in a pattern similar to that of CDw60, or O-acetyl
      GD3. The majority (>70%) of synovial fluid T cells from patients with RA were
      found to be 6C2 positive, and those 6C2+ T cells exhibited a transendothelial
      migratory capacity that was inhibited by pretreatment of T cells with anti-6C2
      mAb. Moreover, treatment of T cells with neuraminidase resulted in a loss of 6C2
      expression as well as a reduction in the transendothelial migratory activity.
      Anti-6C2 mAb reacted specifically with GD3, but not with O-acetyl-GD3. The
      reactivity of anti-6C2 mAb was induced on the cell surface only by transfection
      with cDNA for GD3 synthase. CONCLUSION: The 6C2 molecule is a disialoganglioside,
      GD3, and is present on a subset of T cells with transendothelial migratory
      capacity. The 6C2/GD3 molecules, as well as 6C2/GD3+ T cells, appear to play a
      role in T cell migration and in the inflammation of RA.

PMID- 11229460
TI  - Rheumatoid arthritis in southern Spain: toward elucidation of a unifying role of
      the HLA class II region in disease predisposition.
AB  - OBJECTIVE: To evaluate the contributions of HLA-DQ and -DR polymorphisms to
      susceptibility to rheumatoid arthritis (RA) in a population in southern Spain,
      and to compare the value of the shared epitope (SE) and RA protection (RAP)
      models in accounting for the HLA class II region's contribution to RA
      predisposition. METHODS: One hundred sixty RA patients and 153 healthy controls
      were typed for HLA-DRB1 and -DQB1 using high-resolution DNA techniques.
      Distributions of predisposing DRB1 alleles in patients and control subjects
      according to the SE model were compared with distributions of predisposing DQ and
      protective DERAA-positive DRBI alleles according to the RAP model. RESULTS: DQ3
      (DQBI*03 and *04 combined with DQA1*03) and DQ5 (DQB1*0501/DQA1*0101) alleles
      predisposed individuals to RA independently of SE-positive DRB1 alleles. DQ3/3
      homozygous individuals had the strongest risk of developing RA. DQ3 molecules
      predisposed to RA more than did DQ5 molecules. The weaker predisposition mediated
      by DQ5 included the DRB1*1001-carrying haplotype; no DRB1*1001-homozygous
      patients were observed. DRBI*0401 played a unique role in the contribution of DQ3
      DR4 haplotypes to RA, in spite of its low frequency in southern Spain.
      CONCLUSION: The low prevalences of RA and of mild disease observed in Spain, and
      in southern Europe in general, can be explained in great part by the low
      frequency of DQ3-DR4 haplotypes, especially those carrying DRB1*0401. However,
      the overall distribution of HLA-DQ and -DR alleles in RA patients compared with
      control subjects is similar to that in other European and North American
      populations. A model involving both DQ and DR can best account for the
      contribution of HLA to RA.

PMID- 11229461
TI  - HLA haplotype analysis in Finnish patients with rheumatoid arthritis.
AB  - OBJECTIVE: To further characterize the HLA gene products that play an important
      role in the pathogenesis of rheumatoid arthritis (RA). METHODS: One hundred
      thirty-four haplotypes from 67 Finnish RA patients and 77 control haplotypes were
      analyzed for HLA-DRB1 loci, associated alleles of the HLA-DQB1 locus, alleles of
      the type 2 transporter-associated antigen processing (TAP2) genes, and HLA-B27.
      In addition, a panel of microsatellite markers within the HLA class I and class
      III regions was studied. RESULTS: The frequency of HLA-DRB1*04 in the haplotypes
      of RA patients was found to be 34% (45 of 134) compared with 14% (10 of 72) in
      control haplotypes (P = 0.004). The frequency of HLA-DRB1*13 was decreased in RA
      haplotypes (4%, or 5 of 134) in contrast to control haplotypes (24%, or 17 of 72)
      (P = 0.000031). The decrease in DRB1*13 was not secondary to the increase in
      DRB1*04, since it was also found among DRB1*04-negative haplotypes (P < 0.001).
      The DRB1*13-associated DQB1*0604 allele was similarly decreased in RA haplotypes
      (P = 0.025). The TAP2I allele of I/J dimorphism was increased in RA patients
      (85%, or 114 of 134) as compared with controls (69%, or 49 of 71) (P = 0.011). Of
      the tumor necrosis factor (TNF) microsatellite alleles, TNFa6 and TNFb5 were
      found to be increased in RA haplotypes (for a6 27% versus 5% in controls [P =
      0.00043], and for b5 43% versus 26% in controls [P = 0.037]). CONCLUSION: Both
      protection-associated and susceptibility-associated alleles can be found among
      HLA class II genes, and the results suggest that loci outside DR/DQ may
      contribute to the pathogenesis of RA.

PMID- 11229462
TI  - The association of cigarette smoking with disease outcome in patients with early
      inflammatory polyarthritis.
AB  - OBJECTIVE: Cigarette smoking is known to increase rheumatoid factor (RF) and
      nodule formation in patients with rheumatoid arthritis (RA). In this study, we
      examined the influence of smoking on disease outcome at 3 years among patients
      newly presenting with inflammatory polyarthritis (IP). METHODS: We studied 486
      patients with IP who were referred to the Norfolk Arthritis Register, of whom 323
      (67%) satisfied the American College of Rheumatology 1987 criteria for RA.
      Smoking status was assessed at baseline. Disease outcome was assessed at 3 years,
      using measures of joint inflammation, functional disability, and radiologic
      damage. The influence of smoking on disease outcome was explored using logistic
      regression techniques, with patients who had never smoked as the referent group.
      Results are expressed as odds ratios (ORs), with their 95% confidence intervals
      (95% CIs). RESULTS: Current smokers were significantly more likely to be RF
      positive at baseline (47%) than were ex-smokers (34%) and never smokers (31%).
      After 3 years, rheumatoid nodules were significantly more common in smokers (13%)
      compared with ex-smokers/never smokers (4%), a relationship which persisted after
      adjusting for age and sex (OR 4.07, 95% CI 1.38-12). In contrast, after adjusting
      for age and sex, current smokers had significantly fewer swollen joints (OR 0.61,
      95% CI 0.37-0.98). However, smoking status had no influence on the development of
      erosions or functional disability. CONCLUSION: Despite smokers being more likely
      to develop nodules and to be RF positive, current smokers did not have higher
      levels of radiologic damage, and had fewer swollen joints. We hypothesize that
      this could be due to either the effect of cigarette smoking on the inflammatory
      response or other factors (e.g., reduced physical activity in smokers) which may
      limit joint inflammation and damage.

PMID- 11229463
TI  - Correlation of power Doppler sonography with vascularity of the synovial tissue
      of the knee joint in patients with osteoarthritis and rheumatoid arthritis.
AB  - OBJECTIVE: To examine the significance of power Doppler sonography (PDS) in the
      diagnosis of synovial hypertrophy of the knee joint by verifying and comparing
      the PDS findings with histopathologic findings of synovial membrane vascularity.
      METHODS: The knee joints of 23 patients who were undergoing arthroplasty of the
      knee joint because of osteoarthritis or rheumatoid arthritis were examined with
      ultrasound before arthroplasty. The vascularity of the synovial membrane was
      classified semiquantitatively using PDS. A sample of synovial tissue was obtained
      during the arthroplasty, and the vascularity of the synovial tissue was evaluated
      by immunohistochemistry (factor VIII) and was graded qualitatively by a
      pathologist who was unaware of the PDS findings. The visual qualitative grading
      by the examiner was controlled by analyzing PDS images and histologic samples
      using a digital image evaluation system. RESULTS: The correlation between the
      qualitative PDS results and the qualitative grading of the vascularity by the
      pathologist was 0.89 by Spearman's rho (P < 0.01). The Pearson correlation
      coefficient between the digital analysis of the PDS images and the digital
      analysis of the tissue sections was 0.81 (P < 0.01). Digital image analysis and
      qualitative grading by the examiner had a correlation of 0.89 by Spearman's p (P
      < 0.01) for the PDS images. The correlation between the qualitative estimation of
      vascularity by the pathologist and the digital image analysis was 0.88 by
      Spearman's rho (P < 0.01). CONCLUSION: In the present study, PDS proved to be a
      reliable diagnostic method for qualitative grading of the vascularity of the
      synovial tissue. In clinical practice, PDS allows further differentiation of the
      hypertrophic synovium.

PMID- 11229464
TI  - Development of fulminant hepatitis B (precore variant mutant type) after the
      discontinuation of low-dose methotrexate therapy in a rheumatoid arthritis
      patient.
AB  - A 75-year-old female rheumatoid arthritis patient who was positive for hepatitis
      B surface antigen and for antibodies to hepatitis Be antigen showed liver
      dysfunction, and therefore methotrexate (MTX) therapy was discontinued. Her drug
      lymphocyte stimulation test indicated positivity for MTX. Her liver dysfunction
      improved briefly, but she developed fulminant hepatitis with elevated levels of
      hepatitis B virus (HBV)/DNA polymerase and subsequently died. HBV/DNA analysis
      performed with polymerase chain reaction-mutation site-specific assay revealed
      that the fulminant hepatitis was caused by a precore mutant virus. Sudden
      reactivation of the immune system by discontinuation of MTX may have led to the
      attack on infected cells. Even when hepatitis Be antibodies are present, MTX
      should not be used in patients who have chronic infection with HBV.

PMID- 11229465
TI  - Effects of intraarticular glucocorticoids on macrophage infiltration and
      mediators of joint damage in osteoarthritis synovial membranes: findings in a
      double-blind, placebo-controlled study.
AB  - OBJECTIVE: To investigate the effects of intraarticular glucocorticoid treatment
      on macrophage infiltration, the expression of the chemokines monocyte
      chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein 1alpha (MIP
      1alpha), and the expression of matrix metalloproteinases 1 and 3 (MMPs 1 and 3)
      and their inhibitors, the tissue inhibitors of metalloproteinases 1 and 2 (TIMPs
      1 and 2), in osteoarthritis (OA) synovial membranes. METHODS: Forty patients
      underwent arthroscopic biopsy before and 1 month after intraarticular injection
      of glucocorticoids. Twenty-one patients received 120 mg of methylprednisolone
      acetate (Depo-Medrol; Upjohn, Kalamazoo, MI), and 20 patients received placebo (1
      patient received placebo in 1 knee and methylprednisolone acetate in the other).
      Immunoperoxidase staining for the expression of CD68, MCP-1, MIP-1alpha, MMP-1,
      MMP-3, TIMP-1, and TIMP-2 was performed, and the immunostaining was quantified by
      color video image analysis. RESULTS: CD68, MCP-1, MIP-1alpha, MMP-1, MMP-3, TIMP
      1, and TIMP-2 immunostaining was observed in all synovial membranes.
      Intraarticular glucocorticoid treatment was associated with a small (30%) but
      statistically significant (P = 0.048) reduction in CD68+ macrophage staining in
      the synovial lining layer, but there was no change in the CD68 expression in the
      synovial sublining layer. No significant differences were observed for MCP-1, MIP
      1alpha, MMP-1, MMP-3, TIMP-1, and TIMP-2 immunostaining in the synovial lining or
      sublining layers. CONCLUSION: Intraarticular glucocorticoids may reduce CD68+
      macrophage infiltration into the synovial lining layer, but not the expression of
      MCP-1, MIP-1alpha, MMP-1, MMP-3, TIMP-1, and TIMP-2 in the synovial membrane, in
      patients with OA.

PMID- 11229467
TI  - Low-binding alleles of Fcgamma receptor types IIA and IIIA are inherited
      independently and are associated with systemic lupus erythematosus in Hispanic
      patients.
AB  - OBJECTIVE: To examine the relationship between allelic polymorphisms of IgG
      receptors (FcgammaR) and the development of lupus nephritis in a prospective
      study, and to determine the distribution of FcgammaR haplotypes (FcgammaRIIA and
      FcgammaRIIIA genotypes) in lupus patients and disease-free control subjects.
      METHODS: We studied 67 Hispanic systemic lupus erythematosus (SLE) patients from
      a prospective study of outcome and 53 disease-free control subjects. Patients
      were followed up longitudinally for 3 years. FcgammaRIIA and FcgammaRIIIA
      genotypes were determined using allele-specific polymerase chain reaction.
      RESULTS: Nephritis was present in 28% of patients at entry into the study and in
      69% at the end of 3 years. In the nephritis group (n = 46), as well as the entire
      SLE cohort, there was a predominance of genotypes with low-binding alleles
      (FcgammaRIIa-R131 and FcgammaRIIIa-F176) at both loci (SLE nephritis patients 89%
      versus controls 62%; P < 0.002; odds ratio 0.20 [95% confidence interval 0.05
      0.6] for risk of nephritis in individuals homozygous for either FcgammaRIIa-H131
      or FcgammaRIIIaV176). The frequency of individuals homozygous for high-binding
      alleles at either locus decreased as the burden of disease increased (P < 0.002,
      by Mann-Whitney test). There was no linkage disequilibrium between FcgammaRIIA
      and FcgammaRIIIA in Hispanics, yet in the SLE patients, there was a clear
      overrepresentation of the FcgammaRIIa-R131;FcgammaRIIIa-F176 haplotype (SLE
      patients 48% versus controls 30%) and a decrease in the frequency of the high
      binding haplotype (4% versus 23%) (P < 0.002). CONCLUSION: We observed an
      increase in the frequency of low-binding FcgammaR alleles in an SLE population
      with a high prevalence of renal disease. The apparent selection for the
      FcgammaRIIa-R131;FcgammaRIIIa-F176 haplotype in Hispanic patients suggests that
      low-binding alleles of both FcgammaRIIa and FcgammaRIIIa confer risk for SLE and
      may act additively in the pathogenesis of disease, whereas the high-binding
      haplotype FcgammaRIIa-H131;FcgammaRIIIa-V176 is protective, particularly in the
      homozygous state.

PMID- 11229466
TI  - Interleukin-1beta down-regulates the expression of glucuronosyltransferase I, a
      key enzyme priming glycosaminoglycan biosynthesis: influence of glucosamine on
      interleukin-1beta-mediated effects in rat chondrocytes.
AB  - OBJECTIVE: To assess the variations of galactose-beta-1,3-glucuronosyltransferase
      I (GlcAT-I) expression related to the decrease in proteoglycan synthesis mediated
      by interleukin-1beta (IL-1beta) in rat chondrocytes, and to evaluate the
      influence of glucosamine on the effects elicited by this proinflammatory
      cytokine. METHODS: Rat articular chondrocytes in primary monolayer cultures or
      encapsulated into alginate beads were treated with recombinant IL-1beta in the
      absence or presence (1.0-4.5 gm/liter) of glucosamine. Variations of GlcAT-I and
      expression of stromelysin 1 (matrix metalloproteinase 3 [MMP-3]) messenger RNA
      (mRNA) were evaluated by quantitative multistandard reverse transcriptase
      polymerase chain reaction. In vitro enzymatic activity of GlcAT-I was measured by
      thin-layer chromatography, with radiolabeled UDP-glucuronic acid and a
      digalactoside derivative as substrates. Proteoglycan synthesis was determined by
      ex vivo incorporation of Na2-35SO4. Nitric oxide synthase and cyclooxygenase
      activities were monitored by the evaluation of nitrite (NO2-) and prostaglandin
      E2 (PGE2) produced in the culture medium, respectively. RESULTS: IL-1beta
      treatment resulted in a marked inhibition of GlcAT-I mRNA expression and in vitro
      catalytic activity, together with a decrease in proteoglycan synthesis. In
      addition, glucosamine was able to prevent, in a dose-dependent manner, the
      inhibitory effects of IL-1beta. In the same way, the amino sugar reduced NO2- and
      PGE2 production induced by IL-1beta. Finally, the up-regulation of stromelysin 1
      (MMP-3) mRNA expression by IL-1beta was fully prevented by glucosamine.
      CONCLUSION: The results of this study suggest that the deleterious effect of IL
      1beta on the anabolism of proteoglycan could involve the repression of GlcAT-I, a
      key enzyme in the biosynthesis of glycosaminoglycan. Glucosamine was highly
      effective in preventing these IL-1beta-mediated suppressive effects. The amino
      sugar also prevented the production of inflammatory mediators induced by the
      cytokine. This action could account for a possible beneficial effect of
      glucosamine on osteoarthritic articular cartilage.

PMID- 11229468
TI  - The appearance of U1 RNP antibody specificities in sequential autoimmune human
      antisera follows a characteristic order that implicates the U1-70 kd and B'/B
      proteins as predominant U1 RNP immunogens.
AB  - OBJECTIVE: To observe the order of development of anti-U1 RNP peptide antibodies
      in humans. METHODS: Immunoblots against Jurkat cell lysates were performed on
      5,882 serum samples from 3,668 patients referred on clinical grounds for RNP
      antibody testing to a reference laboratory between 1989 and 1999. In patients
      from whom multiple samples were drawn, we determined the order in which IgG
      antibodies to the U1 RNP peptides A, B'/B, C, D, and 70 kd appeared. RESULTS: One
      hundred sixty-three patients with serial samples were identified in whom
      antibodies to at least one U1 RNP peptide initially were not present but later
      appeared. The first RNP antibodies to appear were most often directed against the
      70 kd and B'/B peptides (P < 0.01). Antibodies to the A and C peptides usually
      developed after other RNP peptide antibodies, and antibodies to D often emerged
      only after immunity to multiple other U1 RNP proteins had appeared. B'/B, but not
      70 kd, was a frequent early target of spreading after initial immunity to other
      RNP peptides. CONCLUSION: Orderly patterns of emergence of U1 RNP peptide
      antibodies appear to exist in humans. Two peptides, 70 kd and B'/B, show
      characteristics of early immunogens in the development of human RNP immunity.

PMID- 11229469
TI  - Anti-topoisomerase I (anti-Scl-70) antibodies in patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: To investigate the presence and clinical significance of anti-Scl-70
      antibodies in patients with systemic lupus erythematosus (SLE). METHODS: Levels
      of antibodies against Scl-70 were determined by a commercial clinical enzyme
      linked immunosorbent assay (ELISA) during routine evaluation. Results were
      verified by an additional ELISA with a characterized bovine Scl-70, by ELISA with
      a recombinant human topoisomerase I, by Western blot, and by double diffusion in
      agar gel. Disease activity was estimated retrospectively by the Systemic Lupus
      Activity Measure (SLAM). RESULTS: Of 128 consecutive SLE patients, 25% were
      positive for anti-Scl-70 antibody; this antibody activity was cognate in nature.
      No SLE patient could be classified as also having systemic sclerosis. The levels
      of anti-Scl-70 were significantly correlated with the SLAM score for the entire
      cohort (r = 0.563, P < 0.001) and for 7 individual patients with multiple
      longitudinal measurements (r = 0.755-0.951, P < 0.001; n = 6) (r = 0.378, P <
      0.05; n = 1). A significant correlation was also found between the levels of anti
      Scl-70 and anti-double-stranded DNA antibodies (r = 0.558, P < 0.001). Patients
      with anti-Scl-70 had significantly higher risk of pulmonary hypertension (P <
      0.01) and renal involvement (P < 0.001) than patients without this antibody.
      CONCLUSION: Anti-Scl-70 antibody is present in a significant subset of patients
      with SLE. For this subset, it offers a good correlate of disease activity and
      suggests increased risk for pulmonary hypertension and nephritis.

PMID- 11229470
TI  - Detection of autoantibodies to killer immunoglobulin-like receptors using
      recombinant fusion proteins for two killer immunoglobulin-like receptors in
      patients with systemic autoimmune diseases.
AB  - OBJECTIVE: To investigate the existence of autoantibodies to killer
      immunoglobulin-like receptors (KIRs), especially p58.1 (KIR2DL1) and p58.2
      (KIR2DL3), in patients with systemic autoimmune diseases. METHODS: Sera from 30
      patients with systemic lupus erythematosus (SLE), 30 patients with rheumatoid
      arthritis (RA), 22 patients with Behcet's disease, and 20 healthy control
      subjects were tested for anti-p58.1 and anti-p58.2 antibodies by Western blot
      analysis using recombinant p58.1 and p58.2 proteins. Furthermore, clinical
      features and laboratory data were compared between the anti-p58.1/58.2 antibody
      positive and -negative patients. RESULTS: Anti-p58.1 antibodies were detected in
      7 (23.3%) of the 30 patients with SLE, 9 (30%) of the 30 patients with RA, and 6
      (27.3%) of the 22 patients with Behcet's disease. Anti-p58.2 antibodies were
      detected in the same 22 patients who were positive for the anti-p58.1 antibodies.
      None of the serum samples from the healthy donors were positive for antibodies to
      the recombinant p58.1 or p58.2 molecules. Compared with the anti-p58.1/ 58.2
      antibody-negative patients, the anti-p58.1/58.2 antibody-positive patients had
      significantly elevated levels of serum IgG in all 3 diseases tested, an
      accelerated erythrocyte sedimentation rate in RA and SLE, and decreased white
      blood cell counts in RA. CONCLUSION: This report is the first to describe the
      presence of autoantibodies to KIR2DL (p58.1 and p58.2) in the sera of patients
      with systemic autoimmune diseases. Considering the correlation with several
      clinical features, these autoantibodies may be involved in the pathologic process
      of the autoimmune diseases.

PMID- 11229471
TI  - The DNA mismatch repair enzyme PMS1 is a myositis-specific autoantigen.
AB  - OBJECTIVE: The specificity of the autoantibody response in different autoimmune
      diseases makes autoantibodies useful for diagnostic purposes. It also focuses
      attention on tissue- and event-specific circumstances that may select unique
      molecules for an autoimmune response in specific diseases. Defining additional
      phenotype-specific autoantibodies may identify such circumstances. This study was
      undertaken to investigate the disease specificity of PMS1, an autoantigen
      previously identified in some sera from patients with myositis. METHODS: We used
      immunoprecipitation analysis to determine the frequency of autoantibodies to PMS1
      in sera from patients with myositis, systemic lupus erythematosus, or scleroderma
      and from healthy controls. Additional antigens recognized by PMS1-positive sera
      were further characterized in terms of their susceptibility to cleavage by
      apoptotic proteases. RESULTS: PMS1, a DNA mismatch repair enzyme, was identified
      as a myositis-specific autoantigen. Autoantibodies to PMS1 were found in 4 of 53
      patients with autoimmune myositis (7.5%), but in no sera from 94 patients with
      other systemic autoimmune diseases (P = 0.016). Additional mismatch repair
      enzymes (PMS2, MLH1) were targeted, apparently independently. Sera recognizing
      PMS1 also recognized several other proteins involved in DNA repair and
      remodeling, including poly(ADP-ribose) polymerase, DNA-dependent protein kinase,
      and Mi-2. All of these autoantigens were efficiently cleaved by granzyme B,
      generating unique fragments not observed during other forms of cell death.
      CONCLUSION: PMS1 autoantibodies are myositis specific. The striking correlation
      between an immune response to a group of granzyme B substrates (functioning in
      DNA repair and remodeling) and the myositis phenotype strongly implies that
      tissue- and event-specific biochemical events play a role in selecting these
      molecules for an autoimmune response. Understanding the role of granzyme B
      cleavage in this response is an important priority.

PMID- 11229472
TI  - Decreased Ras-mitogen-activated protein kinase signaling may cause DNA
      hypomethylation in T lymphocytes from lupus patients.
AB  - OBJECTIVE: Previous studies have shown that inhibiting T cell DNA methylation
      causes a lupus-like disease by modifying gene expression. T cells from patients
      with lupus exhibit diminished levels of DNA methyltransferase (MTase) enzyme
      activity, hypomethylated DNA, and changes in gene expression similar to those
      exhibited by T cells treated with methylation inhibitors, suggesting that DNA
      hypomethylation may contribute to human lupus. Since it is known that DNA MTase
      levels are regulated by the ras-mitogen-activated protein kinase (MAPK) pathway,
      this study sought to determine whether decreased ras-MAPK signaling could account
      for the DNA hypomethylation in lupus T cells. METHODS: DNA MTase messenger RNA
      (mRNA) from lupus patients and from healthy controls was quantitated by Northern
      analysis, and ras-MAPK signaling was determined by immunoblotting with antibodies
      to the activated forms of extracellular receptor-associated kinase (ERK). Results
      were compared with those in T cells in which ras-MAPK signaling was inhibited
      with a soluble inhibitor of MAPK ERK I (MEK1). RESULTS: T cells from patients
      with active lupus had diminished DNA MTase mRNA levels and decreased signaling
      through the ras-MAPK pathway. Inhibiting signaling through the ras-MAPK pathway
      with the MEK1 inhibitor decreased DNA MTase mRNA and enzyme activity to the
      levels seen in lupus T cells, and resulted in DNA hypomethylation resembling that
      seen in lupus T cells. CONCLUSION: These results suggest that a decrease in
      signaling through the ras-MAPK pathway may be responsible for the decreased MTase
      activity and DNA hypomethylation in patients with lupus.

PMID- 11229473
TI  - "Lymphoid" chemokine messenger RNA expression by epithelial cells in the chronic
      inflammatory lesion of the salivary glands of Sjogren's syndrome patients:
      possible participation in lymphoid structure formation.
AB  - OBJECTIVE: Many studies have shown that the microanatomic organization of
      infiltrating leukocytes in the salivary gland lesions of patients with Sjogren's
      syndrome (SS) resembles the structure of lymphoid organs. A newly defined set of
      chemokines referred to as "lymphoid," which orchestrate leukocyte
      microenvironmental homing and contribute to the formation of lymphoid structures,
      provides directional clues. The aim of this study was to investigate the possible
      existence of "lymphoid" chemokines in the chronic inflammatory lesions of SS
      patients and thus validate their potential involvement in the disease process.
      METHODS: Twelve patients with primary SS, 3 patients with secondary SS, 4
      patients with other autoimmune disorders, and 4 control individuals were the
      subjects of this study. Reverse transcriptase-polymerase chain reaction analysis
      was performed in order to examine the messenger RNA (mRNA) expression of
      "lymphoid" chemokines. Furthermore, in situ hybridization studies revealed
      chemokine mRNA localization. Immunohistochemistry was also applied in order to
      identify the cell types that expressed the chemokine mRNA. RESULTS: STCP
      1/monocyte-derived chemokine and TARC mRNA were expressed in the majority of
      patients with primary and secondary SS, in 2 of 4 patients with other autoimmune
      disorders, and in 2 of 4 controls. BCA-1, ELC, and PARC mRNA were only detected
      in patients with primary and secondary SS. SLC mRNA was also detected in 1 non-SS
      patient. The main cellular sources of chemokine mRNA were ductal epithelial cells
      and infiltrating mononuclear leukocytes. CONCLUSION: The expression pattern of
      "lymphoid" chemokine mRNA points further to the role of epithelial cells in the
      pathogenesis of SS and offers new insight into the potential mechanisms that
      could be involved in leukocyte attraction and in the in situ formation of
      secondary lymphoid tissue structures.

PMID- 11229474
TI  - Alteration of peripheral blood dendritic cells in patients with primary Sjogren's
      syndrome.
AB  - OBJECTIVE: We recently identified 3 fractions of human peripheral blood (PB)
      dendritic cells (DC), including the monocyte-associated fractions 1 and 2
      (CD1a+,CD11c+ and CD1a-,CD11c+, respectively) and the lymphoid-associated
      fraction 3 (CD1a-,CD11c-). We attempted to determine whether these fractions were
      altered in Sjogren's syndrome (SS). METHODS: We examined 23 patients with primary
      SS and 22 normal control subjects. DC were purified from PB and analyzed by flow
      cytometry. Immunohistochemical staining of labial salivary glands of SS patients
      was performed with monoclonal antibodies against fascin, which is known to be
      specific for DC. RESULTS: The total numbers of PB DC and fraction 1 DC were
      decreased in SS. Immunohistochemical staining demonstrated that
      fascin+,CD11c+,HLA-DR+ mononuclear cells were present and scattered among
      numerous fascin-hyperfiltrating cells in SS patients. Interferon-gamma (IFNgamma)
      producing Th1 cells were shown to be increased in both PB and salivary glands of
      patients, indicating the presence of general IFNgamma-producing Th1 polarization
      in SS. Furthermore, numbers of Thl cells were increased when naive T cells were
      cocultured with fraction 1 DC in vitro. CONCLUSION: These findings suggest
      selective trafficking of fraction 1 DC into focal sites of inflammation and
      subsequent promotion of Th1 balance, suggesting a novel pathogenesis of SS.

PMID- 11229475
TI  - Treatment with a consensus peptide based on amino acid sequences in
      autoantibodies prevents T cell activation by autoantigens and delays disease
      onset in murine lupus.
AB  - OBJECTIVE: To test the hypothesis that an artificial peptide, based on an
      algorithm describing T cell stimulatory sequences from the VH regions of murine
      IgG antibodies to DNA, is an effective tolerogen in vivo in the (NZB/NZW)F1
      (BWF1) mouse model of systemic lupus erythematosus. METHODS: Using proliferative
      T cell responses to 439 Ig peptides, an algorithm was constructed that describes
      the amino acid sequences likely to stimulate BWF1 T cells. Stimulatory
      (pConsensus [pCONS]) or nonstimulatory (pNegative [pNEG]) peptides were
      synthesized. Groups of 10-week-old (healthy) or 20-week-old (diseased) BWF1 mice
      received monthly intravenous injections of 1,000 microg of peptide or saline. Ex
      vivo splenic T cell responses and in vivo clinical effects were measured.
      RESULTS: Tolerance was induced by pCONS, but not by pNEG, with respect to ex vivo
      T cell proliferation and T cell help for antibodies to DNA. T cell help for IgG
      anti-DNA was impaired not only after T cell stimulation by pCONS but also after
      stimulation by some peptides from nucleosomal and Ro antigens. Treatment with
      pCONS significantly delayed the onset of nephritis and inhibited increases in the
      plasma levels of total IgG, IgG antibodies to DNA, nucleosome, cardiolipin,
      interferon-gamma, and interleukin-4. In contrast, antibody responses to an
      exogenous antigen were not impaired. Survival was significantly prolonged in both
      healthy and diseased mice treated with pCONS. CONCLUSION: Induction of immune
      tolerance in response to treatment with pCONS in autoreactive T cell helper
      populations is highly effective in delaying the appearance of multiple
      autoantibodies, cytokine increases, and nephritis in BWF1 mice, and dramatically
      prolongs survival. A striking effect is the ability of the peptide to tolerize T
      cell help for anti-DNA that is induced by multiple, structurally unrelated self
      antigens.

PMID- 11229476
TI  - Molecular and cellular mediators of interleukin-1-dependent acute inflammatory
      arthritis.
AB  - OBJECTIVE: To examine the molecular and cellular mechanisms in a model of acute
      inflammatory monarticular arthritis induced by methylated bovine serum albumin
      (mBSA) and interleukin-1 (IL-1). METHODS: Mice were injected intraarticularly
      with mBSA on day 0 and subcutaneously with recombinant human IL-1beta on days 0
      2. At day 7, knee joints were removed and assessed histologically. Flow cytometry
      and RNase protection were used to analyze IL-1-dependent events. RESULTS: C57BL/6
      (B6), 129/Sv, and (B6 x 129/ Sv)F1 hybrid mice, all H-2b strains, were
      susceptible to mBSA/IL-1-induced arthritis, whereas C3H/HeJ (H-2k) mice were not.
      B6 mice lacking T and B cells (RAG1-/-) or major histocompatibility complex (MHC)
      class II antigens (MHCII-/-), and B6 mice treated with a CD4+ T cell-depleting
      monoclonal antibody, were resistant to disease. In contrast, B cell-deficient
      (muMT/ muMT) mice developed arthritis at an incidence and severity similar to
      that of controls. RelB-deficient (RelB-/-) bone marrow chimeric mice had
      arthritis that was significantly reduced in incidence and severity. In B6 mice,
      flow cytometry demonstrated an IL-1-dependent leukocyte infiltration into the
      synovial compartment and RNase protection assays revealed induction of messenger
      RNA (mRNA) for the chemokines monocyte chemoattractant protein 1, macrophage
      inhibitory protein 2 (MIP-2), RANTES, MIP-1alpha, and MIP-1beta, in vivo and in
      vitro. CONCLUSION: Arthritis induced by mBSA/IL-1 is strain specific and
      dependent on CD4+ T lymphocytes and at least partially on RelB, but not on B
      lymphocytes or antibody. IL-1 contributes to leukocyte recruitment to the
      synovium and directly induces chemokine mRNA production by synovial cells. This
      model of acute monarticular arthritis is particularly suitable for further
      investigations into cell-mediated immunity in arthritis and the role of IL-1.

PMID- 11229477
TI  - Increased production of intracellular interleukin-1 receptor antagonist type I in
      the synovium of mice with collagen-induced arthritis: a possible role in the
      resolution of arthritis.
AB  - OBJECTIVE: To examine the patterns of production of interleukin-1 receptor
      antagonist (IL-1Ra) isoforms and of IL-1beta during arthritis in vivo. METHODS:
      Arthritis was induced in DBA/1 mice by immunization with type II collagen, and
      the production of IL-1Ra isoforms was examined in whole joints and in dissected
      synovial tissues by reverse transcription-polymerase chain reaction (RT-PCR),
      RNase protection assay, Western blotting, immunostaining, and in situ
      hybridization. Production of IL-1beta also was examined using similar approaches.
      RESULTS: Production of IL-1Ra increased in the joints during collagen-induced
      arthritis (CIA). By RT-PCR, secreted IL-1Ra messenger RNA (mRNA) was detected in
      normal joints, whereas intracellular IL-1Ra type I (icIL-1Ra1) mRNA was only
      produced in inflamed joints. Western blot studies showed that icIL-1Ra1 protein
      levels increased in the joints during the course of CIA and that icIL-1Ra3
      protein was also present in low amounts. RNase protection assays showed that the
      IL-1beta:IL-1Ra mRNA ratio was increased in inflamed joints through day 14 of
      arthritis, whereas a reverse pattern was present at later time points (from day
      20 to day 60). Consistent with this finding, immunohistochemistry and in situ
      hybridization studies confirmed that icIL-1Ra1 was only present in inflamed
      joints. The histologic evaluation of CIA during the course of the disease
      indicated a resolution of acute inflammation, since icIL-1Ra1 production
      increased and the ratio of IL-1beta to total IL-1Ra decreased. CONCLUSION:
      Production of IL-1Ra isoforms, particularly icIL-1Ra1, is stimulated in inflamed
      joints during CIA in mice. The combination of decreased production of IL-1beta
      and elevated levels of icIL-1Ra1 during the course of CIA was associated with a
      reduction in inflammatory activity. These results suggest that icIL-1Ra1 may play
      a role in the resolution of murine CIA.

PMID- 11229478
TI  - Antineutrophil cytoplasmic antibodies reacting with the pro form of proteinase 3
      and disease activity in patients with Wegener's granulomatosis and microscopic
      polyangiitis.
AB  - OBJECTIVE: Antineutrophil cytoplasmic antibodies (ANCA) directed against
      proteinase 3 (PR3) are diagnostic markers for the small vessel vasculitides
      Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA). Correlation of
      disease activity with PR3 ANCA levels, as determined by standard methods, is not
      apparent in every patient. PR3 ANCA react with yet to be identified
      conformational epitopes. We have identified PR3 ANCA subsets that react
      differentially with mature recombinant PR3 (rPR3; lacking the N-terminal
      activation dipeptide) and the pro form of this enzyme (pro-rPR3). The present
      study was performed to determine the association of these PR3 ANCA subsets with
      disease activity. METHODS: Sera from 61 PR3 ANCA-positive patients with WG or MPA
      were assayed by capture enzyme-linked immunosorbent assay using pro-rPR3 and rPR3
      as target antigens, and were correlated with disease activity as determined by
      the Birmingham Vasculitis Activity Score (BVAS). RESULTS: Median levels of PR3
      ANCA reacting with pro-rPR3 were higher during active (n = 32) than during
      inactive (n = 29) disease (P = 0.016). Reactivity with mature rPR3 was not
      significantly different (P = 0.71). Serial followup in individual patients also
      indicated better correlation of PR3 ANCA reactivity with pro-rPR3 than with
      mature rPR3. CONCLUSION: PR3 ANCA subsets reactive with epitopes accessible on
      pro-PR3 correlate better with disease activity than do subsets reactive with
      epitopes accessible only on mature PR3. This observation may explain why ANCA
      levels determined with current standard methods are suboptimal for monitoring
      disease activity. It raises new questions about the primary target of the PR3
      ANCA immune response in patients with small vessel vasculitis.

PMID- 11229479
TI  - Elevated interleukin-4 and interleukin-13 production by T cell lines from
      patients with Churg-Strauss syndrome.
AB  - OBJECTIVE: To investigate cytokine production patterns of T cell lines (TCL) from
      patients with Churg-Strauss syndrome (CSS). METHODS: Short-term polyclonal TCL
      were generated from peripheral blood of patients with CSS or Wegener's
      granulomatosis (WG) and healthy controls (HC). TCL were established in the
      presence of interleukin-2 (IL-2) and phytohemagglutinin and were phenotypically
      characterized by flow cytometry. Th1/ Th2 cytokine production by stimulated TCL
      (72 hours) was analyzed by enzyme-linked immunosorbent assay. RESULTS: TCL that
      represented the progeny of in vivo-activated T cells from CSS patients displayed
      a heterogeneous immunophenotype, with a predominance of CD4+ T cells when
      compared with WG TCL, which were predominantly CD8+. All CSS TCL shared the
      ability to produce large amounts of interferon-gamma (IFNgamma), IL-4, and IL-13
      compared with HC (P = 0.014 for all 3). Production of IL-4 and IL-13 was higher
      in CSS TCL than in WG TCL (P = 0.014 for both). IL-5 production was up-regulated
      in WG TCL compared with CSS TCL (P = 0.014). Compared with HC, WG TCL showed
      increased production of IFNgamma (P = 0.021), IL-5 (P = 0.043), and IL-13 (P =
      0.021). CONCLUSION: Our results indicate that, while there is evidence for both a
      type 1 and a type 2 response in CSS, type 2 cytokine production pattern appears
      to predominate in this disease when compared with WG and HC.

PMID- 11229480
TI  - Blockade of endogenous transforming growth factor beta signaling prevents up
      regulated collagen synthesis in scleroderma fibroblasts: association with
      increased expression of transforming growth factor beta receptors.
AB  - OBJECTIVE: To elucidate the role of transforming growth factor beta (TGFbeta) in
      the increased expression of the collagen gene in scleroderma fibroblasts.
      METHODS: Dermal fibroblasts from 10 patients with diffuse systemic sclerosis
      (SSc) of recent onset and from 10 healthy individuals were studied. The
      production of active and total (active + latent) TGFbeta1 levels from cultured
      dermal fibroblasts was measured using a TGFbeta1 enzyme-linked immunosorbent
      assay system. Expression of the TGFbeta type I and type II receptor proteins in
      dermal fibroblasts was determined by immunoblotting, and the level of expression
      of human alpha2(I) collagen messenger RNA (mRNA) was evaluated by Northern blot
      analysis. The transcriptional activity of the human alpha2(I) collagen gene was
      examined with chloramphenicol acetyltransferase (CAT) assays using the -772
      COL1A2/CAT construct. RESULTS: SSc fibroblasts expressed increased levels of
      TGFbeta type I and type II receptors but secreted amounts of TGFbeta similar to
      those secreted by normal fibroblasts. The blockade of TGFbeta signaling with anti
      TGFbeta antibodies or a TGFbeta1 antisense oligonucleotide abolished the
      increased mRNA expression, as well as the up-regulated transcriptional activity
      of the human alpha2(I) collagen gene in SSc fibroblasts. CONCLUSION: These
      results suggest that TGFbeta plays a crucial role in the pathogenesis of SSc and
      raise the possibility of a therapeutic approach with anti-TGFbeta antibodies or a
      TGF11 antisense oligonucleotide.

PMID- 11229482
TI  - Synovial stimulatory protein fragments copurify with woodchuck hepatitis virus:
      implications for the etiology of arthritis in chronic hepatitis B virus
      infection.

PMID- 11229481
TI  - Widespread pain among 11-year-old Finnish twin pairs.
AB  - OBJECTIVE: To examine the prevalence of widespread musculoskeletal pain (WSP)
      symptoms in 11-year-old Finnish twins and to determine the relative role of
      genetic and environmental factors in the etiology of WSP. METHODS: Data on
      current pain items were collected from 1995 to 1998 from a national sample of
      Finnish families with 11-year-old twins born between 1984 and 1987. The presence
      of WSP was determined using a validated questionnaire method. Pairwise similarity
      was computed for 583 monozygotic (MZ) pairs, 588 same-sex dizygotic (DZ) pairs,
      and 618 opposite-sex DZ twin pairs. Variance components for genetic and
      environmental factors were estimated using biometric structural equation modeling
      techniques. RESULTS: The prevalence of WSP was 9.9%, with no sex difference. The
      majority of twin pairs with WSP were discordant. The tetrachoric correlations for
      male MZ (r = 0.38), male DZ (r = 0.37), female MZ (r = 0.59), female DZ (r =
      0.54), and opposite-sex pairs (r = 0.43) showed little difference by zygosity.
      Female pairs were more concordant than male pairs among both MZ and DZ twins.
      Biometric model-fitting indicated that genetic factors did not account for the
      pattern of twin similarity. Among boys 35%, and among girls 56%, of the variation
      in liability to WSP could be attributed to shared familial environmental effects.
      The remainder was attributed to unshared environmental effects. CONCLUSION:
      Genetic factors seem to play at most a minor role in WSP in 11-year-old twins,
      and environmental factors shared by family members account for a substantial
      proportion of the variability in WSP.

PMID- 11229483
TI  - The rate of recurrence of isolated congenital heart block: a population-based
      study.

PMID- 11229484
TI  - Lupus band test yields negative results in primary antiphospholipid syndrome.

PMID- 11229485
TI  - Monoclonal expansion of B cells in Sjogren's syndrome: comment on the article by
      Martin et al.

PMID- 11229486
TI  - Is the anti-topoisomerase I autoantibody response associated with a distinct
      amino acid sequence in the HLA-DQbeta1 domain?

PMID- 11229488
TI  - USDA releases organic food guidelines.

PMID- 11229487
TI  - Clinical Images: Arthritis induced by South American blastomycosis.

PMID- 11229489
TI  - Federal agencies, Montana reach agreement on Yellowstone bison.

PMID- 11229490
TI  - Standards can bring leading edge closer to home.

PMID- 11229492
TI  - Questions regarding revaccination protocols.

PMID- 11229493
TI  - Another call for scientific evidence of alternative medicine.

PMID- 11229494
TI  - Supports WesternU's approach to education.

PMID- 11229495
TI  - Interested in dietary impact on osteoarthritis.

PMID- 11229497
TI  - Opinions on designated licensure.

PMID- 11229496
TI  - Opinions on designated licensure.

PMID- 11229498
TI  - Opinions on designated licensure.

PMID- 11229499
TI  - Opinions on designated licensure.

PMID- 11229500
TI  - Developing an ethic for the handling, restraint, and discipline of companion
      animals in veterinary practice.

PMID- 11229501
TI  - Animal behavior case of the month. A Goffin's cockatoo was examined because it
      had been avoiding the female owner for the past 3 months.

PMID- 11229502
TI  - Postexposure rabies prophylaxis protocol for domestic animals and epidemiologic
      characteristics of rabies vaccination failures in Texas: 1995-1999.
AB  - OBJECTIVE: To determine whether postexposure rabies prophylaxis (PEP) in domestic
      animals, as mandated by the state of Texas, has continued to be effective and to
      evaluate PEP and preexposure rabies vaccination failures from 1995 through 1999.
      DESIGN: Retrospective study. ANIMALS: 830 unvaccinated domestic animals (621
      dogs, 78 horses, 71 cats, and 60 cattle) that received PEP and 4 animals (3 dogs
      and 1 horse) that had preexposure rabies vaccination failure. PROCEDURE: Zoonotic
      incident case reports from 1995 through 1999 were reviewed for information
      regarding unvaccinated domestic animals that received PEP according to state
      protocol after exposure to a rabid animal; reports were also reviewed for
      information regarding preexposure rabies vaccination failures. The PEP
      recommendations were to immediately vaccinate the animal against rabies, isolate
      the animal for 90 days, and administer booster vaccinations during the third and
      eighth weeks of the isolation period. Rabies vaccines used in the PEP protocol
      were administered via the route prescribed by the USDA. RESULTS: From 1995
      through 1999, 830 animals received PEP; 4 failures were recorded. Additionally, 4
      preexposure rabies vaccination failures were recorded. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results of this study indicate that an effective PEP protocol for
      unvaccinated domestic animals exposed to rabies includes immediate vaccination
      against rabies, a strict isolation period of 90 days, and administration of
      booster vaccinations during the third and eighth weeks of the isolation period.
      This PEP schedule has proven to be effective for control of rabies in domestic
      animals.

PMID- 11229503
TI  - Measurement of serum concentrations of free thyroxine, total thyroxine, and total
      triiodothyronine in cats with hyperthyroidism and cats with nonthyroidal disease.
AB  - OBJECTIVE: To determine the usefulness of measuring serum free thyroxine (T4)
      concentration as a diagnostic test for hyperthyroidism in cats, and to determine
      the influence of nonthyroidal disease on free T4 concentration in cats without
      hyperthyroidism. DESIGN: Prospective case series. ANIMALS: 917 cats with
      untreated hyperthyroidism, 221 cats with nonthyroidal disease, and 172 clinically
      normal cats. PROCEDURE: Serum free T4, total T4, and total triiodothyronine (T3)
      concentrations were measured in cats with untreated hyperthyroidism and cats with
      nonthyroidal disease. Serum total T4 and T3 concentrations were determined by use
      of radioimmunoassay, and free T4 concentration was measured by use of direct
      equilibrium dialysis. Reference ranges for hormone concentrations were
      established on the basis of results from the 172 clinically normal cats. RESULTS:
      Sensitivity of serum free T4 concentration as a diagnostic test for
      hyperthyroidism was significantly higher than the test sensitivity of either
      total T4 or T3 concentration. Of the 221 cats with nonthyroidal disease, 14 had a
      high free T4 concentration (ie, false-positive result). Therefore, calculated
      specificity of measuring serum free T4 concentration as a diagnostic test for
      hyperthyroidism was significantly lower than test specificity of measuring either
      the total T4 or T3 concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      indicate that determination of free T4 concentration is useful in the diagnosis
      of hyperthyroidism, especially in cats in which hyperthyroidism is suspected but
      total T4 and T3 concentrations are within reference ranges. However, because some
      cats with nonthyroidal disease have high serum free T4 concentrations,
      hyperthyroidism should not be diagnosed solely on the finding of high free T4
      concentration.

PMID- 11229504
TI  - Constrictive pericarditis secondary to Coccidioides immitis infection in a dog.
AB  - A 4-year-old castrated male mixed-breed dog with a history of coccidioidomycosis
      was referred for evaluation of abdominal and pleural effusion. Results of
      radiography, ultrasonography, cytologic evaluation of thoracic fluid, and
      serologic testing supported a diagnosis of constrictive pericarditis secondary to
      infection with Coccidioides immitis. Aggressive treatment for presumptive
      coccidioidomycosis was begun, but the dog's condition continued to deteriorate,
      and the dog was euthanatized. At necropsy, the pericardium was thicker than
      normal and fibrotic and adhered to the epicardium. Microscopically, the
      pericardium and 1 section of epicardium contained lymphoplasmacytic infiltrates
      with a few macrophages and neutrophils. Coccidioides immitis was cultured from
      pericardial fluid. A search of records from the Arizona Veterinary Diagnostic
      Laboratory for 1988 through 1998 revealed that of 46 dogs in which a diagnosis of
      coccidioidomycosis was confirmed at necropsy, 13 had involvement of the heart or
      pericardium.

PMID- 11229505
TI  - Intraosseous approach to the nasolacrimal duct for removal of a foreign body in a
      dog.
AB  - A Labrador retriever was evaluated because of chronic mucopurulent discharge from
      the left eye. A foreign body was identified in the nasolacrimal duct by use of
      dacryocystorhinography. Attempts to alleviate the inflammation by use of flushing
      and administration of antimicrobials were unsuccessful. At surgery, the
      infraorbital foramen was used as a landmark for a skin incision, because the
      nasolacrimal duct courses dorsal and parallel to the infraorbital canal. An air
      drill was used to remove the portion of the maxillary bone overlying the
      nasolacrimal duct, which exposed the intraosseous portion of the duct and allowed
      removal of a plant-material foreign body. The incision in the duct was allowed to
      heal by second intention, and the dog recovered without complications.

PMID- 11229506
TI  - Influence of drug treatment on survival of dogs with immune-mediated hemolytic
      anemia: 88 cases (1989-1999).
AB  - OBJECTIVE: To evaluate association of various treatments for immune-mediated
      hemolytic anemia with survival to discharge in dogs. DESIGN: Retrospective cross
      sectional analysis. ANIMALS: 88 dogs with idiopathic immune-mediated hemolytic
      anemia. PROCEDURE: Medical records of dogs with immune-mediated hemolytic anemia
      treated between August 1989 and August 1999 were examined. Survival to discharge,
      PCV at referral, autoagglutination, and drug treatment and dosage were recorded.
      RESULTS: Treatments included administration of prednisone, dexamethasone,
      azathioprine, danazol, cyclosporine, cyclophosphamide, bovine hemoglobin
      solution, and human immunoglobulin. Overall mortality rate was 50.5%. Significant
      associations with death were not detected for use of azathioprine, cyclosporine,
      danazol, or human immunoglobulin. A significant difference in mortality rate was
      not detected between use of multiple immunosuppressive drug treatments and use of
      single immunosuppressive drugs. Use of cyclophosphamide and bovine hemoglobin
      solution were associated with significant increases in relative risk of death
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that use of cyclophosphamide
      and bovine hemoglobin solution in treatment of idiopathic immune-mediated
      hemolytic anemia may be associated with increased risk of death.

PMID- 11229508
TI  - Retrograde ejaculation in a stallion.
AB  - Retrograde ejaculation was diagnosed in a 10-year-old Arabian stallion. Despite
      behavioral signs consistent with ejaculation, the collection receptacle of an
      artificial vagina remained devoid of semen on numerous occasions. Catheterization
      of the urinary bladder yielded large numbers of spermatozoa, even when an
      ejaculate was obtained, whereas low numbers (< 1 X 10(6)/ml) of spermatozoa are
      found in the bladder of clinically normal stallions after ejaculation. Endoscopic
      examination of the urethra, seminal colliculus, and bladder failed to reveal
      abnormalities. Medical treatment with imipramine hydrochloride apparently
      resulted in improvement initially, but was not curative. Further diagnostic and
      treatment measures were declined and the stallion was castrated. For stallions
      that seemingly fail to ejaculate or for ejaculates that contain lower seminal
      volumes or numbers of spermatozoa than expected, obtaining a urine sample after
      ejaculation via bladder catheterization is a simple diagnostic procedure that may
      be used to investigate the possibility of retrograde ejaculation.

PMID- 11229507
TI  - Treatment with a combination of doxorubicin, surgery, and radiation versus
      surgery and radiation alone for cats with vaccine-associated sarcomas: 25 cases
      (1995-2000).
AB  - OBJECTIVE: To compare use of doxorubicin, surgery, and radiation versus surgery
      and radiation alone for treatment of cats with vaccine-associated sarcoma.
      DESIGN: Retrospective study. ANIMALS: 25 cats with vaccine-associated sarcomas.
      PROCEDURE: Time to first recurrence and survival time were compared between the 2
      treatment groups. The number of surgeries (1 or > 1) were compared with respect
      to time to first recurrence and survival time. RESULTS: Median time to first
      recurrence was 661 days for the group that received doxorubicin, surgery, and
      radiation. Median time to first recurrence has not yet been attained for the
      group treated with surgery and radiation alone. Median survival time was 674 days
      for the group treated with doxorubicin, surgery, and radiation and 842 days for
      the group treated with surgery and radiation alone. For time to first recurrence
      and survival time, significant differences were not detected between cats that
      had 1 surgery and those that had > 1 surgery. CONCLUSIONS AND CLINICAL RELEVANCE:
      Significant differences between the 2 treatment groups were not detected. The
      efficacy of doxorubicin in the treatment of vaccine-associated sarcomas is
      uncertain.

PMID- 11229509
TI  - Treatment of methicillin-resistant Staphylococcus epidermidis infection following
      repair of an ulnar fracture and humeroradial joint luxation in a horse.
AB  - A 27-month-old Rocky Mountain Horse was examined because of a fracture of the
      proximal portion of the ulna and luxation of the humeroradial joint (Monteggia
      fracture). Open reduction was performed, using a mechanical distractor, and the
      ulnar fracture was stabilized by application of a bone plate and screws. After
      surgery, the horse developed an infection of the surgical site, and bacterial
      culture of fluid from the surgical site yielded a pure growth of methicillin
      resistant Staphylococcus epidermidis susceptible to oxytetracycline,
      erythromycin, rifampin, and vancomycin. Treatment with oxytetracycline did not
      result in a favorable clinical response. Therefore, the horse was treated
      systemically with vancomycin and rifampin, and vancomycin-impregnated polymethyl
      methacrylate beads were implanted at the surgical site. Six months after surgery,
      the horse was sound at a walk or trot, and bony union was evident on radiographs
      of the elbow joint.

PMID- 11229510
TI  - Putative uremic encephalopathy in horses: five cases (1978-1998).
AB  - OBJECTIVE: To determine historical, physical examination, clinicopathologic, and
      postmortem findings in horses with putative uremic encephalopathy. Design
      Retrospective study. Animals-5 horses with renal failure and neurologic disease
      not attributable to abnormalities in any other organ system. PROCEDURE: Medical
      records from 1978 to 1998 were examined for horses with renal disease and
      neurologic signs not attributable to primary neurologic, hepatic, or other
      diseases. Signalment, history, physical examination findings, clinicopathologic
      data, renal ultrasonographic findings, and postmortem data were reviewed.
      RESULTS: Of 332 horses with renal disease, 5 met selection criteria. Historical
      findings, physical examination findings, clinicopathologic data, ultrasonographic
      data, and postmortem findings were consistent with chronic renal failure. Swollen
      astrocytes were detected in all 4 horses examined at necropsy. CONCLUSIONS AND
      CLINICAL RELEVANCE: A single criterion was not determined to be pathognomonic for
      uremic encephalopathy in horses. Uremic encephalopathy should be considered as a
      differential diagnosis in horses with evidence of chronic renal failure and
      encephalopathic neurologic sign not attributable to other causes. Astrocyte
      swelling, which was common to all 4 horses examined at necropsy, may serve as a
      microscopic indicator of uremic encephalopathy in horses.

PMID- 11229511
TI  - Use of systemic disease signs to assess disease severity in dairy cows with acute
      coliform mastitis.
AB  - OBJECTIVE: To evaluate the use of systemic disease signs for classifying severity
      of acute coliform mastitis in dairy cows. DESIGN: Prospective cohort study.
      ANIMALS: 144 dairy cows. PROCEDURE: Cows were examined at the time of initial
      identification of disease (time 0) and classified as having mild, moderate, or
      severe disease on the basis of rectal temperature, hydration status, rumen
      contraction rate, and attitude. A CBC and serum biochemical analyses were
      performed, and milk samples were submitted for bacterial culture at time 0 and 48
      hours later. RESULTS: 69 cows were classified as having mild disease, 44 as
      having moderate disease, and 31 as having severe disease. Median WBC and
      neutrophil counts were significantly lower in cows with moderate or severe
      disease at time 0 than in cows with mild disease. Band neutrophil count was
      significantly higher at 48 hours and serum calcium concentration was
      significantly lower at time 0 and at 48 hours in cows with severe or moderate
      disease, compared with cows with mild disease. Twenty-eight, 51, and 77% of cows
      with mild, moderate, and severe disease, respectively, had > 100,000 colony
      forming units/ml of milk at time 0. The odds that a cow with severe disease would
      die or be culled were 3.6 times the odds for a cow with moderate disease and 11.2
      times the odds for a cow with mild disease. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results suggest that a classification scheme based on readily observable systemic
      disease signs can be used to classify disease severity in cows with acute
      coliform mastitis.

PMID- 11229512
TI  - Grayanotoxin poisoning in three goats.
AB  - Six Nubian goats were exposed to an azalea branch (Rhododendron indica) at the
      Riverbanks Zoological Park in Columbia, South Carolina. The following day, 3 of
      the 6 goats were referred to the veterinary hospital of the Riverbanks Zoological
      Park with bloat, profuseregurgitation, and signs of depression, intermittent head
      pressing, and fine muscle tremors in the hind limbs. The goats were treated with
      magnesium hydroxide, activated charcoal, and lactated Ringer's solution and
      recovered within 24 hours. Definitive diagnosis of grayanotoxin exposure was
      accomplished by use of liquid chromatography-mass spectrometry analysis of urine
      and fecal samples. Rhododendron spp are members of the Ericaceae (Heath) family
      and may contain grayanotoxins, which exert toxic effects by binding to sodium
      channels in cell membranes and increasing the permeability of sodium ions in
      excitable membranes. Rhododendron poisoning should be considered in animals with
      clinical evidence of gastrointestinal tract irritation, cardiac arrhythmias, and
      neurologic signs.

PMID- 11229514
TI  - The development of a multitarget, multicolor fluorescence in situ hybridization
      assay for the detection of urothelial carcinoma in urine.
AB  - The purpose of this study was to develop a multitarget, multicolor fluorescence
      in situ hybridization (FISH) assay for the detection of urothelial carcinoma (UC)
      in urine specimens. Urinary cells obtained from voided urine specimens of 21
      patients with UC and 9 normal donors were analyzed with nine different centromere
      enumeration probes and a single locus-specific indicator probe to determine an
      optimal set of FISH probes for UC detection. The four probes with the greatest
      sensitivity for UC detection were then labeled with a unique fluorophore and
      combined into a single probe set. The probes with the greatest combined
      sensitivity for UC detection were CEP3, CEP7, CEP17, and the 9p21 (P16) LSI. This
      probe set was used to evaluate urine specimens acquired from 179 patients for
      prospective testing (46 with biopsy-proven UC). FISH slides were evaluated by
      scanning the slide for cells with nuclear features suggestive of malignancy and
      assessing the FISH signal pattern of these cells for polysomy (ie, gains of two
      or more different chromosomes). A receiver operator characteristic curve revealed
      that a cutoff of 5 cells with polysomy as the positive criterion for cancer
      resulted in an overall sensitivity of 84.2% for patients with biopsy-proven UC
      and a specificity of 91.8% among patients with genitourinary disorders but no
      evidence of UC. This study demonstrates that a multitarget, multicolor FISH assay
      containing centromeric probes to chromosomes 3, 7, and 17 and a locus-specific
      probe to band 9p21 has high sensitivity and specificity for the detection of UC
      in voided urine specimens.

PMID- 11229515
TI  - Reproducibility of alternative probe synthesis approaches for gene expression
      profiling with arrays.
AB  - Before gene expression profiling with microarray technology can be transferred to
      the diagnostic setting, we must have alternative approaches for synthesizing
      probe from limited RNA samples, and we must understand the limits of
      reproducibility in interpreting gene expression results. The current gold
      standard of probes for use with both microarrays and high-density filter arrays
      are synthesized from 1 microg of purified poly(A)+ RNA. We evaluated two
      approaches for synthesizing cDNA probes from total RNA with subsequent
      hybridization to high-density filter arrays: 1) reverse transcription (RT) of 5
      microg total RNA and 2) RT-polymerase chain reaction (RT-PCR) of 1 microg total
      RNA, using the SMART system. The reproducibility of these two approaches was
      compared to the current gold standard. All three methods were highly
      reproducible. Triplicate experiments resulted in the following concordance
      correlation coefficients to evaluate reproducibility: 0.88 for the gold standard,
      0.86 for cDNA probe synthesized by RT from total RNA, and 0.96 for the SMART cDNA
      probe synthesized from total RNA. We also compared the expression profile of 588
      genes for the total RNA methods to that obtained with the gold standard. Of 150
      positive genes detected by the gold standard, 97 (65%) were detected by cDNA
      probe synthesized by RT of total RNA, and 122 (81%) were detected by the SMART
      cDNA probe. We conclude that SMART cDNA probe produces highly reproducible
      results and yields gene expression profiles that represent the majority of
      transcripts detected with the gold standard.

PMID- 11229513
TI  - Angiotensin I-converting enzyme: genotype and disease associations.

PMID- 11229516
TI  - Novel polymorphism in the FMR1 gene resulting in a "pseudodeletion" of FMR1 in a
      commonly used fragile X assay.
AB  - The fragile X syndrome is the most commonly inherited cause of mental
      retardation. Genetic diagnosis of this disease relies on the detection of triplet
      repeat expansion in the FMR1 gene on the X chromosome. Although the majority of
      disease in fragile X patients is due to mutations involving triplet repeat
      expansion, deletion of various portions of FMR1 has also been described in
      association with the fragile X syndrome. Here we describe a rare polymorphism in
      the noncoding region of FMR1 that mimics detection of a deletion in a commonly
      used assay for fragile X syndrome, which can result in misdiagnosis of the
      disease.

PMID- 11229518
TI  - Improving the detection of p53 mutations in breast cancer by use of the FASAY, a
      functional assay.
AB  - The aim of this investigation was to examine the ability of the yeast-based
      functional assay, the functional analysis for the separation of alleles in yeast
      (FASAY), to detect p53 mutations in breast cancers when compared with
      immunohistochemistry and automated sequencing of the whole p53 gene (exons 1-11).
      To achieve this, all three methods were carried out on a cohort of aggressive
      breast tumors. In those tumors, in which the FASAY analysis indicated the
      presence of a mutation, cDNA was extracted from red yeast colonies and was
      sequenced to identify the base change in the p53 gene. The FASAY detected all 24
      mutations found in the series of 48 tumors, whereas initial automated sequencing
      of genomic DNA detected 18/24 mutations. A second round of automated sequencing
      carried out using an independent source of genomic DNA detected mutations in 3 of
      the 6 tumors that originally appeared to lack a mutation in genomic DNA. All but
      1 of the mutations originally missed by sequencing of genomic DNA were point
      mutations. Five mutations in this series (21%) were outside the commonly
      investigated exons 5-8, reinforcing the need to extend sequencing beyond this
      region. Of 24 tumors, 14 had strong immunohistochemical staining, and all 14 had
      p53 mutations; the majority of mutations missed by immunohistochemistry produced
      a truncated protein. Strong staining was not seen in tumors lacking a p53
      mutation. The FASAY proved to be a rapid, reliable, and effective method for
      identifying those breast tumors harboring p53 mutations.

PMID- 11229517
TI  - Specificity of TLS-CHOP rearrangement for classic myxoid/round cell liposarcoma:
      absence in predominantly myxoid well-differentiated liposarcomas.
AB  - Myxoid liposarcoma (LS), the most common subtype of LS, is known to be
      characterized by the specific t(12;16) resulting in a TLS-CHOP fusion in almost
      all cases. We wished to address the following questions: (i) Is this genetic
      hallmark also present in other types of LS with predominant myxoid change? (ii)
      What is the proportion of cases with the variant EWS-CHOP fusion? (iii) What is
      the optimal approach for Southern blot detection of TLS breakpoints? We
      identified 59 LS characterized histologically by >90% myxoid component, in which
      frozen tissue tumor was available for DNA extraction. These 59 LS with myxoid
      features were divided into 2 groups: 42 LS with classic myxoid/round cell
      appearance (myxoid LS) and 17 well-differentiated LS (WDLS) with a predominant
      (>90%) myxoid component. Within the myxoid LS group, 29 tumors were low grade and
      13 high grade (>20% round cell component). Among the 17 predominantly myxoid
      WDLS, there were 15 low grade and 2 focally high grade tumors. In addition, we
      selected as control group, 20 LS of other histological types with minimal or no
      myxoid change (17 WDLS and 3 pleomorphic LS) and 13 myxofibrosarcomas. Southern
      blot analysis was performed in all cases using a CHOP cDNA probe, and in all CHOP
      rearranged cases using a TLS cDNA probe. Probe/enzyme combinations for Southern
      blot analysis were CHOP exon 3-4 cDNA probe with BamHI or SacI, TLS exon 3-6 cDNA
      probe with BclI. All 42 cases of myxoid LS showed a CHOP rearrangement and 38 of
      them also had a TLS rearrangement. Among the 4 myxoid LS without Southern blot
      evidence of TLS rearrangement, 1 showed an EWS-CHOP fusion by Southern blotting
      and reverse transcriptase-polymerase chain reaction and in another case, reverse
      transcriptase-polymerase chain reaction detected a TLS-CHOP fusion transcript.
      None of the predominantly myxoid WDLS and none of the tumors included in the
      control group showed rearranegements with CHOP probe. In addition, 12
      predominantly myxoid WDLS, 10 other LS, and 5 myxofibrosarcoma from the control
      group were also tested for TLS rearrangement; all were negative. The TLS-CHOP
      fusion is highly sensitive and specific for the entity of classic myxoid/round
      cell LS. Other types of LS, even with a predominant myxoid component, lack the
      TLS-CHOP rearrangement, confirming that they represent a genetically distinct
      group of LS. The prevalence of the EWS-CHOP variant fusion was approximately 2%
      in this series. The optimal enzyme for TLS genomic breakpoint detection is BclI.

PMID- 11229520
TI  - Analytical evaluation of primer engineered multiplex polymerase chain reaction
      restriction fragment length polymorphism for detection of factor V Leiden and
      prothrombin G20210A.
AB  - Factor V Leiden and prothrombin G20210A are clinically relevant genetic risk
      factors for venous thrombosis. Analysis for both mutations is increasingly being
      performed on patients exhibiting hypercoagulability. The goal of the current
      study was to evaluate the performance of primer-engineered multiplex polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the
      simultaneous detection of factor V Leiden and prothrombin G20210A. Primer
      engineered multiplex PCR-RFLP methods for the detection of factor V Leiden and
      prothrombin G20210A from the medical literature were reviewed. A modified method
      was optimized in which both mutations generate HindIII RFLPs and the prothrombin
      amplicon contains an invariant HindIII recognition site to assess the
      completeness of endonuclease digestion. Digested amplification products were
      analyzed by agarose gel electrophoresis in a single gel lane and visualized by
      ethidium bromide. Primer-engineered multiplex PCR-RFLP was used to analyze 205
      human genomic DNA samples whose factor V Leiden genotypes had been previously
      determined by MnlI PCR-RFLP. Complete concordance for factor V Leiden genotypes
      was observed between the two methods in the 205-sample cohort comprising 139 wild
      type, 62 heterozygous mutant, and four homozygous mutant individuals. For
      prothrombin G20210A, primer-engineered multiplex PCR-RFLP identified 196 wild
      type and nine heterozygous mutant individuals in the 205-sample cohort. To
      independently verify prothrombin genotypes, the nine heterozygous mutants and an
      additional 11 wild-type patient samples (representing 10% of patient samples)
      were subjected to DNA sequencing. Complete concordance was observed between DNA
      sequencing and primer-engineered multiplex PCR-RFLP results. In further
      validation, 123 of the DNA samples consisting of four heterozygous mutant and 119
      wild type individuals were genotyped with the Invader Assay for Factor II
      (prothrombin G20210A). Results showed 100% concordance between the Invader Assay
      and primer-engineered multiplex PCR-RFLP. A primer-engineered multiplex PCR-RFLP
      based on single restriction endonuclease digestion has been evaluated and shown
      to simultaneously and accurately detect factor V Leiden and prothrombin G20210A
      mutations. The method is robust and readily adaptable to the clinical molecular
      diagnostic laboratory.

PMID- 11229519
TI  - Pseudo-spikes are common in histologically benign lymphoid tissues.
AB  - T cell receptor gene rearrangement is a classic marker of T cell clonality and is
      a useful adjunct in the diagnosis of T cell lymphomas and leukemias. Rearranged V
      J gene segments amplified by polymerase chain reaction (PCR) are traditionally
      analyzed by polyacrylamide gel electrophoresis. We and others have analyzed TCR
      gamma PCR products using capillary gel electrophoresis, which produces single
      nucleotide resolution and provides improved diagnostic sensitivity over
      conventional methods. However, with this marked increase in resolution and
      sensitivity, it is necessary to re-define normal variation of TCR-gamma gene
      rearrangement in control tissues to allow appropriate interpretation of
      monoclonality if present. Using DNA capillary gel electrophoresis, we examined
      the spectrum of normal patterns for TCR-gamma in a variety of T-cell-rich,
      histologically benign tissue types, including spleen, lymph node, tonsil, and
      blood, and compared this with the patterns in T cell lymphoma samples. We defined
      relative peak heights as h1/h2, where h1 represents the peak height of the
      largest peak above the normally distributed population, and h2 represents the
      peak height of the normally distributed curve. We found spikes in almost 20% of
      histologically benign samples with relative peak heights that were more than 0.5
      and up to 1.5. We designated these as pseudo-spikes, because they may be mistaken
      for monoclonal spikes. In contrast, the relative peak height of the T cell
      lymphoma samples that showed clonal rearrangement was much higher than that of
      the pseudo-spikes, being at least 2 in 11/11 and at least 3 in 10/11 cases. Our
      data suggest that peaks with relative height of at least 3 represent a true
      clonal population in diagnostic samples. Peaks with relative heights of less than
      1.5 may be insignificant, while peaks with relative heights between 1.5 to 3 may
      warrant further evaluation. Although capillary gel electrophoresis is superior in
      assessing T cell clonality, caution must be exercised when interpreting results,
      because pseudo-spikes appear to be common in benign tissues with lymphoid
      populations and are not necessarily indicative of clonal malignant T cell
      population.

PMID- 11229522
TI  - Highlights of the Ninth Annual Beaumont Symposium on Molecular Pathology: DNA
      technology in the clinical laboratory.

PMID- 11229521
TI  - Performance characteristics of a quantitative, homogeneous TaqMan RT-PCR test for
      HCV RNA.
AB  - We developed a homogeneous format reverse transcription-polymerase chain reaction
      assay for quantitating hepatitis C virus (HCV) RNA based on the TaqMan principle,
      in which signal is generated by cleaving a target-specific probe during
      amplification. The test uses two probes, one specific for HCV and one specific
      for an internal control, containing fluorophores with different emission spectra.
      Titers are calculated in international units (IU)/ml by comparing the HCV signal
      generated by test samples to that generated by a set of external standards.
      Endpoint titration experiments demonstrated that samples containing 28 IU/ml give
      positive results 95% of the time. Based on these data, the limit of detection was
      set conservatively at 40 IU/ml. All HCV genotypes were amplified with equal
      efficiency and accurately quantitated: when equal quantities of RNA were tested,
      each genotype produced virtually identical fluorescent signals. The test
      exhibited a linear range extending from 64 to 4,180,000 IU/ml and excellent
      reproducibility, with coefficients of variation ranging from 21.6 to 30.4%, which
      implies that titers that differ by a factor of twofold (0.3 log10) are
      statistically significant (P = 0.005). The test did not react with other
      organisms likely to co-infect patients with hepatitis C and exhibited a
      specificity of 99% when evaluated on a set of samples from HCV seronegative blood
      donors. In interferon-treated patients, the patterns of viral load changes
      revealed by the TaqMan HCV quantitative test distinguished responders from
      nonresponders and responder-relapsers. These data indicate that the TaqMan
      quantitative HCV test provides an attractive alternative for measuring HCV viral
      load and should prove useful for prognosis and for monitoring the efficacy of
      antiviral treatments.

PMID- 11229523
TI  - Links between cell-surface events involving redox-active copper and gene
      regulation in the hemopexin heme transport system.
AB  - Heme is considered to play an instrumental role in the pathology of hemolysis,
      trauma, and reperfusion following ischemia. However, data are sparse and
      experimental models are required. The transport of heme by hemopexin to tissues
      is a specific, membrane receptor-mediated process. Hemopexin recycles after
      endocytosis like transferrin. Heme oxygenase-1 (HO-1), transferrin, the
      transferrin receptor, and ferritin are regulated by heme-hemopexin. Genes that
      encode proteins important for cellular defenses against oxidative stress, such as
      the cysteine-rich metallothioneins (MTs), are also activated by hemopexin, as are
      proteins that regulate cell cycle control including p21WAF1 and the tumor
      suppressor p53. The hemopexin system is being investigated to establish how
      intracellular events are affected by signal(s) from the plasma membrane due to
      hemopexin receptor occupancy and heme transport. A transient oxidative
      modification of proteins, shown by carbonyl production, takes place. Redox
      processes at the cell surface, which generate cuprous ions, are involved in the
      regulation of the MT-1 and HO-1 genes by heme-hemopexin before heme catabolism
      and intracellular release of iron. The "redox-sensitive" transcription factors
      activated by the hemopexin system include c- Jun, RelA/NFkappaB and MTF-1. The
      specific copper chelator bathocuproine disulfonate prevents carbonyl production,
      the nuclear translocation of MTF-1, and the induction of MT-1 revealing a novel,
      pivotal role for copper in the hemopexin system. In addition, surface redox
      active copper is the first link shown for the concomitant regulation of HO-1 and
      MT-1 and is required for the activation of the amino-terminal c-Jun kinase (JNK)
      by heme-hemopexin.

PMID- 11229525
TI  - Functions of vitamin C as a mediator of transmembrane electron transport in blood
      cells and related cell culture models.
AB  - Vitamin C (ascorbic acid) is an important physiological antioxidant. Within
      cells, it is practically always present in the reduced form. Several enzymatic
      and nonenzymatic mechanisms have been reported to maintain this status. In the
      extracellular environment, oxidation of ascorbate leads to loss of vitamin
      because the oxidized form, dehydroascorbic acid, is unstable under physiological
      conditions. The intermediate ascorbate free radical, although rather long-lived
      for a free radical, quickly disproportionates into the two other forms, also
      leading to loss of vitamin. Protection from loss can only be achieved by cellular
      regeneration mechanisms, i.e., by uptake of dehydroascorbic acid and either
      storage or recycling, and by plasma-membrane mediated reduction of extracellular
      free radical or dehydroascorbic acid. Moreover, intracellular ascorbate can also
      serve as an electron donor for transmembrane reduction of external electron
      acceptors. However, the physiological significance of this function is as yet
      unknown. The results presented in the literature are sometimes conflicting as to
      the relative contributions of these different possibilities, which seem to differ
      in different cell types. In this short review, the various pathways of
      regeneration of ascorbate and their relative contributions to the avoidance of
      vitamin loss in plasma or cell culture medium are discussed.

PMID- 11229524
TI  - Cell membrane redox systems and transformation.
AB  - Cell membrane redox systems carry electrons from intracellular donors and
      transport them to extracellular acceptors. This phenomenon appears to be
      universal. Numerous reviews have emphasized not only the bioenergetic mechanisms
      of redox systems but also the antioxidant defense mechanisms in which they
      participate. Moreover, significant progress has been made in the modulation of
      the membrane redox systems on cell proliferation. Because membrane redox systems
      play a key role in the regulation of cell growth, they need to be somehow linked
      into the signaling pathways resulting in either controlled or unregulated growth
      by both internal and external signals. Ultimately, these sequential events lead
      to either normal cell proliferation or cancer cell formation. However, much less
      is known about the involvement of membrane redox in transformation or
      tumorgenesis. In this review, the facts and ideas are summarized concerning the
      redox systems and tumorgenesis in several aspects, such as the regulation of cell
      growth and the effect on cell differentiation and on signaling pathways. In
      addition, information on a unique tumor-associated nicotinamide adenine
      dinucleotide (NADH) oxidase (tNOX) protein is reviewed.

PMID- 11229526
TI  - Plasma membrane NADH-oxidoreductase system: a critical review of the structural
      and functional data.
AB  - The observation in the early 1970s that ferricyanide can replace transferrin as a
      growth factor highlighted the major role plasma membrane proteins can play within
      a mammalian cell. Ferricyanide, being impermeant to the cell, was assumed to act
      at the level of the plasma membrane. Since that time, several enzymes isolated
      from the plasma membrane have been described, which, using NADH as the
      intracellular electron donor, are capable of reducing ferricyanide. However,
      their exact modes of action, and their physiological substrates and functions
      have not been solved to date. Numerous hypotheses have been proposed for the role
      of such redox enzymes within the plasma membrane. Examples include the regulation
      of cell signaling, cell growth, apoptosis, proton pumping, and ion channels. All
      of these roles may be a result of the function of these enzymes as cellular redox
      sensors. The emergence of many diverse roles for ferricyanide utilizing redox
      enzymes present in the plasma membrane might also, in part, be due to the
      numerous redox enzymes present within the membrane; the poor molecular
      characterization of the enzymes may be the reason for some of the diverging
      results reported in the literature as various researchers may be working on
      different enzymes. Here we review the diverse proposals given for structure and
      function to the plasma membrane NADH-oxidoreductase system(s) with a specific
      focus on those enzyme activities which can couple ferricyanide and NADH. Although
      they are still ill-defined enzymes, evidence is rising that they are of utmost
      significance for cellular regulation.

PMID- 11229527
TI  - Plasma membrane redox system in the control of stress-induced apoptosis.
AB  - The plasma membrane of animal cells contains an electron transport system based
      on coenzyme Q (CoQ) reductases. Cytochrome b5 reductase is NADH-specific and
      reduces CoQ through a one-electron reaction mechanism. DT-diaphorase also reduces
      CoQ, although through a two-electron reaction mechanism using both NADH and
      NADPH, which may be particularly important under oxidative stress conditions.
      Because reduced CoQ protects membranes against peroxidations, and also maintains
      the reduced forms of exogenous antioxidants such as alpha-tocopherol and
      ascorbate, this molecule can be considered a central component of the plasma
      membrane antioxidant system. Stress-induced apoptosis is mediated by the
      activation of plasma membrane-bound neutral sphingomyelinase, which releases
      ceramide to the cytosol. Ceramide-dependent caspase activation is part of the
      apoptosis pathway. The reduced components of the plasma membrane antioxidant
      system, mainly CoQ, prevent both lipid peroxidation and sphingomyelinase
      activation. This results in the prevention of ceramide accumulation and caspase 3
      activation and, as consequence, apoptosis is inhibited. We propose the hypothesis
      that antioxidant protective function of the plasma membrane redox system can be
      enough to protect cells against the externally induced mild oxidative stress. If
      this system is overwhelmed, intracellular mechanisms of protection are required
      to avoid activation of the apoptosis pathway.

PMID- 11229528
TI  - High-capacity redox control at the plasma membrane of mammalian cells: trans
      membrane, cell surface, and serum NADH-oxidases.
AB  - The high capacity of proliferating mammalian cells to transfer electrons from
      cytosolic NADH to extracellular electron acceptors like oxygen is poorly
      understood and not widely recognized. Nevertheless, trans-plasma membrane
      electron transport (plasma membrane redox control) probably ranks alongside the
      Na+/H+ antiport system (pH control) and glucose transport in facilitating
      cellular responses to physiological stimuli. These plasma membrane transport
      systems are acutely responsive to receptor ligation by growth factors,
      polypeptide hormones, and other cell activators. A novel tetrazolium-based cell
      proliferation assay that we have shown to measure an NADH-oxidoreductase
      component of the trans-plasma membrane electron transport system has allowed
      direct comparisons with NADH:ferricyanide-oxidoreductase and respiratory burst
      NADPH-oxidoreductase. In addition, an NAD(P)H-oxidase at the cell surface and an
      NADH-oxidase activity in body fluids can be measured by modifying the basic cell
      proliferation assay. As determined by reduction of the cell-impermeable
      tetrazolium reagent, WST-1, electron transfer across the plasma membrane of
      dividing cells can exceed that of fully activated human peripheral blood
      neutrophils. Cellular reduction of WST-1 is dependent on the presence of an
      intermediate electron acceptor and is inhibited by superoxide dismutase (SOD) and
      by oxygen, implying indirect involvement of superoxide in WST-1 reduction. Cell
      surface NAD(P)H-oxidase and serum NADH-oxidase are shown to be distinct from
      trans-plasma membrane NADH-oxidoreductase by their differential sensitivity to
      capsaicin and pCMBS. The glycolytic metabolism of cancer cells may be linked to
      changes in trans-plasma membrane NADH:WST-1-oxidoreductase activity and to
      increased serum NADH-oxidase in cancer.

PMID- 11229529
TI  - Troglitazone protects human erythrocytes from oxidant damage.
AB  - The antidiabetic drug troglitazone contains the active chromanol ring of alpha
      tocopherol, which should give it antioxidant properties within cells. In these
      studies, the antioxidant effects of troglitazone were tested in human
      erythrocytes and in their ghosts. Troglitazone bound to erythrocyte ghosts in a
      linear manner and was retained even after centrifugation washes. In response to
      an oxidant stress generated by a water-soluble free radical initiator,
      troglitazone that was bound to erythrocyte ghosts was oxidized, but induced a lag
      phase in the disappearance of endogenous alpha-tocopherol and in the appearance
      of lipid hydroperoxides. Troglitazone also delayed loss of endogenous alpha
      tocopherol and hemolysis in washed intact erythrocytes in response to free
      radical-induced extracellular oxidant stress. To mimic exposure of erythrocytes
      to lipid hydroperoxides in vivo, erythrocytes were incubated with phospholipid
      liposomes that contained small amounts of preformed lipid hydroperoxides. This
      induced an oxidant stress in both the liposomes and cells. Troglitazone in
      concentrations above 4 microM almost completely prevented further appearance of
      lipid hydroperoxides in the liposomes, and also completely preserved alpha
      tocopherol in the erythrocytes. The present results suggest that troglitazone
      will help to prevent peroxidative damage to erythrocytes in areas of excessive
      oxidant stress in the vascular bed.

PMID- 11229530
TI  - NADH and NADPH-dependent reduction of coenzyme Q at the plasma membrane.
AB  - High affinity for NADH, and low affinity for NADPH, for reduction of endogenous
      coenzyme Q10 (CoQ10) by pig liver plasma membrane is reported in the present
      work. CoQ reduction in plasma membrane is carried out, in addition to other
      mechanisms, by plasma membrane coenzyme Q reductase (PMQR). We show that PMQR
      catalyzed reduction of CoQ0 by both NADH and NADPH is accompanied by generation
      of CoQ0 semiquinone radicals in a superoxide-dependent reaction. In the presence
      of a water-soluble vitamin E homologue, Trolox, this reduction leads to quenching
      of the Trolox phenoxyl radicals. The involvement of PMQR versus DT-diaphorase
      under the conditions of vitamin E and selenium sufficiency and deficiency was
      evaluated for CoQ reduction by plasma membranes. The data presented here suggest
      that both nucleotides (NADH and NADPH) can be accountable for CoQ reduction by
      PMQR on the basis of their physiological concentrations within the cell. The
      enzyme is primarily responsible for CoQ reduction in plasma membrane under normal
      (nonoxidative stress-associated) conditions.

PMID- 11229531
TI  - Coenzyme Q protects cells against serum withdrawal-induced apoptosis by
      inhibition of ceramide release and caspase-3 activation.
AB  - Coenzyme Q10 (CoQ10) is a component of the antioxidant machinery that protects
      cell membranes from oxidative damage and decreases apoptosis in leukemic cells
      cultured in serum-depleted media. Serum deprivation induced apoptosis in CEM-C7H2
      (CEM) and to a lesser extent in CEM-9F3, a subline overexpressing Bcl-2. Addition
      of CoQ10 to serum-free media decreased apoptosis in both cell lines. Serum
      withdrawal induced an early increase of neutral-sphingomyelinase activity,
      release of ceramide, and activation of caspase-3 in both cell lines, but this
      effect was more pronounced in CEM cells. CoQ10 prevented activation of this
      cascade of events. Lipids extracted from serum-depleted cultures activated
      caspase-3 independently of the presence of mitochondria in cell-free in vitro
      assays. Activation of caspase-3 by lipid extracts or ceramide was prevented by
      okadaic acid, indicating the implication of a phosphatase in this process. Our
      results support the hypothesis that plasma membrane CoQ10 regulate the initiation
      phase of serum withdrawal-induced apoptosis by preventing oxidative damage and
      thus avoiding activation of downstream effectors as neutral-sphingomyelinase and
      subsequent ceramide release and caspase activation pathways.

PMID- 11229532
TI  - Cell-surface NAD(P)H-oxidase: relationship to trans-plasma membrane NADH
      oxidoreductase and a potential source of circulating NADH-oxidase.
AB  - The surface of mammalian cells faces an oxidizing environment that has the
      potential to damage proteins, lipids, and carbohydrates to which it is exposed.
      In contrast, the cytoplasm is reducing and its redox state is tightly regulated.
      Trans-plasma membrane oxidoreductases that shift electrons from cytosolic NADH to
      external electron acceptors such as oxygen are widely involved in cellular redox
      control. They reduce oxygen to water and may generate reactive oxygen species
      such as superoxide and hydrogen peroxide. In addition, external NAD(P)H-oxidases
      have been demonstrated on intact cells and as eluted proteins, but the
      relationship between trans-plasma membrane NADH-oxidoreductases and cell-surface
      NAD(P)H-oxidases is not known. To investigate further the relationship between
      plasma membrane NAD(P)H-oxidoreductases, and to gain insight into the
      physiological functions of these redox active membrane proteins, we have adapted
      a simple colorimetric assay for measuring the trans-plasma membrane NADH
      oxidoreductase activity of viable cells to measure NAD(P)H-oxidase at the cell
      surface in real time. Using the cell-impermeable tetrazolium salt WST-1 in the
      presence of NADH or NADPH, but in the absence of an intermediate electron
      acceptor, we show that cell-surface NAD(P)H-oxidase is widely expressed on
      mammalian cells, being more abundant on rapidly proliferating cells than on
      resting neutrophils and spleen cells. The ratio of cofactor dependence of NAD(P)H
      oxidase (NADH:NADPH) varied widely between different cells (0.7-5.2), suggesting
      a family of cell surface oxidases or that the activity of these enzymes may be
      modulated in various ways. Comparison of NAD(P)H-oxidase on the surface of viable
      cells with trans-membrane NADH-oxidoreductase, measured with WST-1 in the
      presence of 1-methoxy PMS, showed that cell-surface NAD(P)H-oxidase was
      differentially inhibited by the cell-impermeable thiol-blocking agent pCMBS, but
      was unaffected or stimulated by other thiol blocking agents. Capsaicin, which
      inhibits trans-plasma membrane NADH-oxidoreductase activity, stimulated surface
      NAD(P)H-oxidase. Metabolic inhibitors had little effect on surface NAD(P)H
      oxidase activity but inhibited trans-plasma membrane activity. These results do
      not support the view the surface NAD(P)H-oxidase is a terminal oxidase for trans
      plasma membrane NADH-oxidoreductase.

PMID- 11229534
TI  - Photosensitization and redox signaling.
AB  - The effect of light in combination with a chemical or a natural compound is
      termed photosensitization, and is known to have multiple cellular effects. Among
      them, modulation of gene expression is one of the most important, because it
      directly influences cell adaptation to novel environmental conditions. In
      previous years, the cis- and trans-acting genetic elements responsible for gene
      regulation by radiation and photosensitization, in particular, have been well
      characterized. The molecular mechanisms involved in the cell response revealed
      that an important control occurs at the transcriptional level and is coordinated
      by various transcription factors. The extracellular or intracellular changes
      mediated by photosensitization are detected by several signal transduction
      networks, allowing cells to mount an appropriated response in term of gene
      regulation. Mitogen-activated protein kinases (MAPK) and phosphatidylinositol 3
      kinases (PI3-K) are among the most thoroughly studied of signal transduction
      systems and have been shown to participate in a diverse array of cellular
      programs. In this review, we will show how these cascades can be activated by
      photosensitization. A third signal type of transduction machinery, which has been
      shown to be activated by photosensitization, is the one leading to the activation
      of the Rel/NF-kappaB family of transcription factors. This family includes many
      members, most of which can form DNA-binding homo- or heterodimers. We will show
      that molecular mechanisms leading to NF-kappaB activation by photosensitization
      are initiated by oxidative damage. While the exact nature of the transduction
      intermediates is still unknown, NF-kappaB activation by radiation followed
      different pathways from those used by pro-inflammatory cytokines.

PMID- 11229533
TI  - A light-responsive and periodic NADH oxidase activity of the cell surface of
      Tetrahymena and of human buffy coat cells.
AB  - Oxidation of external NADH (NADH is an impermeant substrate) by cells of
      Tetrahymena pyriformis oscillated with a period of 24-26 min. The period length
      in darkness (25.6 min) appeared to be slightly longer than the period in light
      (approximately 24 min). When Tetrahymena were placed in darkness for 30-50 min
      and then returned to light, a new maximum in the rate of NADH oxidation was
      observed 36-38 min (13 + 24) min after the beginning of the light treatment. The
      cell-surface NADH oxidase of human buffy coats (a mixture of white cells and
      platelets) also was periodic and light responsive.

PMID- 11229535
TI  - Effect of zinc ions on the cytotoxicity induced by the amyloid beta-peptide.
AB  - Insoluble aggregates of the amyloid beta-peptide (A beta) are a major constituent
      of senile plaques found in brains of Alzheimer's disease patients. The beta
      amyloid fragment A beta(1-40) is toxic to rat pheochromocytoma PC12 cells,
      leading to a concentration-dependent decrease in the reduction of 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The detrimental
      effects of A beta(1-40) are enhanced in the presence of 1 mM zinc, whereas 50
      microM zinc exerts a protective effect against A beta(1-40)-induced toxicity.
      Exposure of PC12 cells to low zinc concentrations (50 microM) affords a decrease
      (1.4-fold) in the extent of lipid peroxidation, a decrement in protein oxidation
      (1.1-fold), and an increase in ATP levels (1.2-fold), although the differences
      were not statistically significant. However, treatment of cells with high
      concentrations of zinc (1 mM) led to significant increases in lipid peroxidation
      (3.7-fold) and protein oxidation (1.5-fold) and to depletion of the ATP pool (21
      fold). These data suggest that zinc has a concentration-dependent dual effect,
      protective and toxic, thus playing an important role in the pathogenesis of
      Alzheimer's disease.

PMID- 11229536
TI  - Coenzyme Q10, vitamin E, and dihydrothioctic acid cooperatively prevent diene
      conjugation in isolated low-density lipoprotein.
AB  - Coenzyme Q (Q10) and alpha-tocopherol cooperatively delay the onset of diene
      conjugation in isolated human low density lipoprotein if supplied in water
      soluble preparations to blood serum. Both copper ions and morpholino sydnonimine
      (in the presence of glucose; SIN-1-glucose) -driven diene conjugation is
      measurable as soon as both reduced Q10 and tocopherol are oxidized, where
      tocopherol oxidation starts after 80-90% consumption of reduced Q10. LDL-bound
      Q10 in turn can be rapidly reduced by dihydrolipoic acid (thioctic acid). This
      reaction is at least 10 times faster than reduction by ascorbic acid.

PMID- 11229537
TI  - Depolarization-associated iron release with abrupt reduction in pulmonary
      endothelial shear stress in situ.
AB  - This study evaluated the roles of endothelial cell membrane potential and
      reactive oxygen species (ROS) in the increase of tissue free iron during lung
      ischemia. Oxygenated ischemia was produced in the isolated rat lung by
      discontinuing perfusion while ventilation with O2 was maintained. We have shown
      previously that tissue oxygenation is maintained in this model of ischemia and
      that biochemical changes are the result of an abrupt reduction in endothelial
      shear stress. With 1 hr oxygenated ischemia, generation of ROS, evaluated by
      oxidation of dichlorodihydrofluorescein (H2DCF) to fluorescent
      dichlorofluorescein, increased 8.0-fold, lung thiobarbituric acid reactive
      substances (TBARS) increased 3.4-fold, and lung protein carbonyl content
      increased 2.4-fold. Lung tissue free iron, measured in the lung homogenate with a
      fluorescent desferrioxamine derivative, increased 4.0-fold during ischemia.
      Pretreatment of lungs with thapsigargin abolished the increase in free iron with
      ischemia indicating that this effect is dependent on Ca2+ release from
      intracellular stores. Perfusion of lungs with high (25 mM) K+ to depolarize the
      endothelium also led to a significant increase in tissue free iron. Pretreatment
      of lungs with 35 microM cromakalim, a K+-channel agonist, significantly inhibited
      both ischemia-induced tissue oxidant injury and the increase in free iron with
      ischemia or with high K+ perfusion. A similar increase in free iron was observed
      when lungs were ventilated with either O2 or N2 during the ischemic period or
      were pre-perfused with an inhibitor of ROS production (diphenyleneiodonium).
      These results indicate that ROS generation is not required for ischemia-mediated
      iron release. Thus, ROS generation and iron release with ischemia are independent
      although both are subsequent to endothelial cell membrane depolarization.

PMID- 11229539
TI  - Singlet oxygen-dependent hydroxyl radical formation during uroporphyrin-mediated
      photosensitization in the presence of NADPH.
AB  - The conversion of singlet oxygen ((1)O2) to hydroxyl radical (*OH) during
      photosensitization of uroporphyrin (UP) in the presence of NADPH was examined by
      a spin-trapping technique with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO).
      Significant electron spin resonance (ESR) signals of DMPO-OH adduct were observed
      during irradiation of the UP-NADPH system with visible light. Scavengers of *OH
      reduced the signal intensity to 3-30% of control, indicating that more than 70%
      of DMPO-OH results from freely diffusing *OH. The ESR signal was almost
      completely lost when quenchers of (1)O2 were added, and was enhanced when the
      amount of deutrated solvent was increased. The appearance of (1)O2, as determined
      by the oxidation of 2,2,6,6-tetramethyl-4-piperidone (TEMPD), was delayed with an
      increase in the concentration of NADPH, whereas the production of *OH was
      upregulated. These observations indicate that conversion of (1)O2 to *OH occurs
      quickly in the presence of NADPH. Hydrogen peroxide (H2O2) was produced (1)O2
      dependently during irradiation of UP in the presence of NADPH. However, neither
      catalase nor desferrioxamine decreased the DMPO-OH signal, and addition of H2O2
      did not increase the signal. SOD increased the signal only slightly. These
      results suggest that the production of *OH from (1)O2 involves neither superoxide
      anion radical nor H2O2.

PMID- 11229538
TI  - Induction of peroxiredoxins in transplanted livers and demonstration of their in
      vitro cytoprotection activity.
AB  - Peroxiredoxin (Prx)-I and -II belong to a new class of antioxidants. Here, we
      report that they are induced by ischemia/reperfusion (I/R) in transplanted
      livers. Hypothesizing that Prxs are induced to protect liver from oxidative
      damage, we transduced these human genes into murine NIH-3T3 cells. The
      overexpressed Prxs made the cells more resistant to t-butylhydroperoxide-induced
      apoptosis. These results indicate that Prx-I and Prx-II are induced by the
      transplantation process and can protect cells against oxidant damage in tissue
      culture. Thus, proper genetic manipulations of Prxs may be useful in increasing
      the success rate of organ transplantation.

PMID- 11229540
TI  - Aging exacerbates hydrogen peroxide-induced alteration of vascular reactivity in
      rats.
AB  - Reactive oxygen species (ROS) such as superoxide anion (O2-*) and hydrogen
      peroxide (H2O2) can be produced by vascular endothelium and smooth muscle cells
      under diverse physiological and pathophysiological situations. These species are
      known to exert various deleterious effects by which they might induce changes in
      vascular reactivity. The aim of the present study was to evaluate the evolution
      of vascular susceptibility to H2O2 during aging in rats. Catalase activity was
      assessed in aortas from young adult (4 months) and aged (24 months) Wistar rats.
      In parallel experiments, isolated rings from both age groups were exposed to
      increasing doses of H2O2 (0, 0.1, 1, 5, or 10 mM) for 20 min and the residual
      vascular response to phenylephrine (PE = 10(-6) M) and acetylcholine (ACh = 10(
      6) M) was evaluated. Our results indicate that aging increases aortic catalase
      activity (4 months: 0.20 +/- 0.02 IU/mg prot versus 24 months: 0.46 +/- 0.06
      IU/mg prot, p < 0.001) while it exacerbates vascular sensitivity to H2O2. These
      results suggest that the observed increased H2O2-induced alterations of vascular
      reactivity during aging in rats might be due to increased sensitivity of the
      vasculature to ROS rather than to a decrease in the defense systems against these
      species.

PMID- 11229541
TI  - Redox 2000: the 5th international conference on plasma membrane redox systems and
      their role in biological stress and disease.

PMID- 11229542
TI  - Meeting highlights of Cardiovascular Radiation Therapy III.

PMID- 11229543
TI  - Comparison of brachytherapy strategies based on dose-volume histograms derived
      from quantitative intravascular ultrasound.
AB  - PURPOSE: We present in this paper the comparison, by simulation, of different
      treatment strategies based either on beta- or gamma-sources, both with and
      without a centering device. Ionizing radiation to prevent restenosis is an
      emerging modality in interventional cardiology. Numerous clinical studies are
      presently being performed or planned, but there is variability in dose
      prescription, and both gamma- and beta-emitters are used, leading to a wide range
      of possible dose distributions over the arterial vessel wall. This paper
      discusses the potential merits of dose-volume histograms (DVH) based on three
      dimensional (3-D) reconstruction of electrocardiogram (ECG)-gated intravascular
      ultrasound (IVUS) to compare brachytherapy treatment strategies. MATERIALS AND
      METHODS: DVH describe the cumulative distribution of dose over three specific
      volumes: (1) at the level of the luminal surface, a volume was defined with a
      thickness of 0.1 mm from the automatically detected contour of the highly
      echogenic blood-vessel interface; (2) at the level of the IVUS echogenic media
      adventitia interface (external elastic lamina [EEL]), an adventitial volume was
      computed considering a 0.5-mm thickness from EEL; and (3) the volume encompassed
      between the luminal surface and the EEL (plaque + media). The IVUS data used were
      recorded in 23 of 31 patients during the Beta Energy Restenosis Trial (BERT)
      conducted in our institution. RESULTS: On average, the minimal dose in 90% of the
      adventitial volume was 37 +/- 16% of the prescribed dose; the minimal dose in 90%
      of the plaque + media volume was 58 +/- 24% and of the luminal surface volume was
      67 +/- 31%. The minimal dose in the 10% most exposed luminal surface volume was
      296 +/- 42%. Simulations of the use of a gamma-emitter and/or a radioactive
      source train centered in the lumen are reported, with a comparison of the
      homogeneity of the dose distribution. CONCLUSIONS: It is possible to derive DVH
      from IVUS, to evaluate the dose delivered to different parts of the coronary
      wall. This process should improve our understanding of the mechanisms of action
      of brachytherapy.

PMID- 11229544
TI  - Effects of low-dose-rate beta-irradiation on vascular smooth muscle cells:
      comparison with high-dose-rate exposure.
AB  - PURPOSE: Radiation therapy is undergoing extensive preclinical and clinical
      testing as a new tool to reduce restenosis after vessel injury. To date, however,
      no definite dose threshold has been identified after radioactive stent
      implantation. In this study, we compared the in vitro response of pig vascular
      smooth muscle cells (SMC) to conventional high-dose-rate (HDR) irradiation with
      the response to continuous low-dose rate (LDR) that could result from exposure to
      a radioactive stent. MATERIALS AND METHODS: Catheter-based radiotherapy delivers
      single doses at HDR whereas radioactive stents use a continuous LDR approach.
      Single doses in excess of 10 Gy have clearly shown a reduction in neointima
      formation and negative vessel remodeling in several animal models. Because dose
      rate is an important parameter modulating the overall biological response to
      ionizing radiation, we have compared the in vitro response of pig aortic SMC at
      conventional HDR (1.5 Gy/min) and at LDR (0.675 Gy/h). RESULTS: SMC showed
      significant repair of sublethal DNA damage and about twice the dose was necessary
      at the LDR to produce the same effect as that seen at the HDR. CONCLUSION: In
      vitro SMC exhibit a significant dose-rate effect that indicates that radioactive
      stents could deliver the dose at a sufficiently high dose rate to compensate for
      cell proliferation while at the same time the total dose should be increased to
      account for sublethal damage repair. This finding has important implications for
      the design of a radioactive stent.

PMID- 11229545
TI  - Tolerance of normal rabbit femoral arteries to single high dose external beam
      irradiation.
AB  - PURPOSE: We gave high single doses of external radiation to normal vessels to
      produce vascular injury and establish the dose tolerance in an animal model. We
      also performed immunohistochemical staining for macrophages and smooth muscle
      cells to assess qualitative changes in their populations. METHODS: Following
      direct bilateral inguinal cutdown in New Zealand white rabbits, single doses of
      15, 20 and 30 Gy were delivered to one vessel. At predetermined time intervals
      following treatment, the animals underwent angiography and were sacrificed. Both
      systems were harvested and analyzed, and their luminal and medial areas compared.
      RESULTS: No statistically significant differences were found between any
      treatment vessel and its contralateral control at any time point. In addition, no
      alterations in subintimal or medial content of macrophages or smooth muscle cells
      were observed. CONCLUSIONS: Our data suggest that single radiation doses as high
      as 30 Gy appear to be well tolerated in the normal, uninjured rabbit vessel over
      a 6-month follow-up. However, the use of a diseased vessel model and longer
      follow-up times need to be studied to provide a better clinical understanding of
      the basic radiobiology of this technique.

PMID- 11229546
TI  - Supplemental oxygen does not synergize with intracoronary radiation for the
      prevention of restenosis in porcine coronary arteries.
AB  - PURPOSE: Recurrence of obstructive coronary arterial lesions (restenosis) after
      angioplasty remains a significant clinical problem. Ionizing radiation, at doses
      >10 Gy administered locally to the angioplasty site, has been shown to inhibit
      restenosis in porcine coronary arteries, but lower doses are ineffective. Methods
      that will allow delivery of lower doses of radiation while retaining the
      antirestenotic efficacy observed at the higher doses are desirable. Hypoxic cells
      are known to be radioresistant; accordingly, we hypothesized that increasing
      blood oxygenation through the use of the TherOx Aqueous Oxygen system would lower
      the doses of endovascular radiation required for the prevention of restenosis.
      MATERIALS AND METHODS: Five swine were studied as follows: balloon injury +
      oxygen alone was performed in two swine. Each swine had a balloon overstretch
      injury in two arteries, left anterior descending (LAD) and either right coronary
      artery (RCA) or left circumflex (LCX) artery (three arteries total). Balloon
      injury + oxygen followed by intracoronary irradiation was performed in a further
      three swine (six arteries). Controls consisted of arteries treated with 0, 5, or
      15 Gy of 192Ir alone. RESULTS: Arteries treated with the TherOx Aqueous Oxygen
      system alone were indistinguishable from arteries treated without oxygenation
      except for a larger adventitial area (5.29 +/- 0.20 vs. 2.77 +/- 0.28 mm2; p <
      0.05). Arteries treated with the TherOx Aqueous Oxygen system along with 5 Gy of
      192Ir exhibited a greater injury-corrected intimal area than arteries treated
      with radiation alone (0.76 +/- 0.18 vs. 0.33 +/- 0.08 mm2; p < 0.05). Neither
      thrombosis rate nor thrombus area was significantly different in arteries
      receiving the TherOx Aqueous Oxygen as compared with controls. CONCLUSIONS: The
      TherOx Aqueous Oxygen system is safe in the context of balloon overstretch
      injury, but decreases the antirestenotic efficacy of 5 Gy of 192Ir. These
      findings suggest that hypoxia does not seem to be a major contributor to the dose
      of radiation required for suppression of neointima, at least when using
      noncentered gamma radiation delivery systems.

PMID- 11229547
TI  - Dose perturbations by high atomic number materials in intravascular
      brachytherapy.
AB  - PURPOSE: In intravascular brachytherapy, use of high atomic number materials,
      such as contrast agents and metallic stents, can introduce significant dose
      perturbations, especially for low energy photons. The purpose of this study is to
      investigate dose perturbation at the interfaces of high atomic number materials
      and tissue. METHODS: To investigate this issue, the radial dose functions across
      the interface between different materials and soft tissue were calculated by
      using Monte Carlo simulations. Various interfaces, including contrast agent to
      water, stainless steel to water, and bone (simulating a calcified plaque) to
      water, were investigated for photon energies between 20 keV and 1 MeV. RESULTS:
      It was found that the dose to water near the interface is enhanced considerably
      by photons of energies between 0.020 and 0.200 MeV. For example, the maximum dose
      enhancement factors for the Hypaque-tissue interface ranged from 2.2 to 18.3 for
      photons in this energy range. The enhancement factor is almost equal to 1 for
      photon energy between 0.400 and 1.000 MeV. It appears that the maximum
      enhancement occurs around 60 keV. For 60-keV photons, the maximum dose
      enhancement factors are about 18.3, 18.7, 19.1, and 3.1 for Hypaque, Omnipaque,
      stainless steel, and calcified plaque, respectively. The dose enhancement
      decreases exponentially with distance from the interface. The affected tissue
      thickness is dependent on the photon energy. As expected, the higher the photon
      energy is, the larger is the affected tissue thickness. Depending on the type of
      interface and the energy of photons, the dose enhancement distance (defined as
      the thickness receiving more than twice the dose without interface) ranges from
      1.3 to 72 microm for photons of energy from 0.020 to 0.100 MeV, respectively.
      CONCLUSIONS: The existense of high atomic number materials could introduce
      significant dose enhancement at the interfaces between these materials and
      tissue. This dose enhancement can be higher than an order of magnitude for photon
      energies around 60 keV, and should be considered in evaluation of the efficacy of
      intravascular brachytherapy.

PMID- 11229548
TI  - Characterization of the dose perturbation by stents as a function of X-ray beam
      energy.
AB  - PURPOSE: External beam irradiation of coronary arteries has been shown to be
      detrimental in an animal model for the prevention of neointimal hyperplasia in
      the presence of stents when orthovoltage x-ray beams are used. The present study
      investigated the effect of beam energy on the dose distribution in the wall of
      the artery in the presence of stents. MATERIALS AND METHODS: We used 250-kVp x
      rays and 6-MV x-rays to irradiate a stent placed in a homogeneous phantom.
      Radiochromic film densitometry and Monte Carlo calculations were used to measure
      and to simulate the dose distribution in the proximity of the stent. RESULT:
      External beam irradiation not only failed to prevent neointimal hyperplasia, but
      actually accentuated the neointimal response to a prompt mechanical injury in the
      artery. The photoelectric effect, which dominates low-energy x-ray interactions,
      produces recoil electrons in the stent, which enhance the dose surrounding the
      intima. The photoelectrons generated in nickel and iron have an extremely short
      range in normal tissue, approximately 0.1 mm. Initial estimates of orthovoltage x
      ray interactions with the stent indicate a dose enhancement in the orthovoltage
      range by a factor of 2-6 due to the rise in the photoelectric cross section in
      this energy range depending on the elemental composition of the stent. Film
      densitometry verifies this dose enhancement. The Monte Carlo calculation yields a
      dose enhancement and the dose fall-off with distance from the stent when
      irradiated with orthovoltage x-rays. Conversely when the tissue and stent are
      irradiated with megavoltage x-rays, the dose enhancement in this region is a
      factor of 1.15 in close proximity to the stent and 1.0 at distances greater than
      0.1 mm. The 6-MV photon interactions in tissue and Ni/Ti are predominantly
      through Compton scattering. The Compton effect is dependent on the electron
      density in the medium, in contrast to the atomic number, which is more relevant
      for photoelectric absorption. The dose estimates for megavoltage x-rays adjacent
      to the stent are complicated by the lack of charged particle equilibrium.
      CONCLUSIONS: There is a limited but definite increase in the dose delivery to the
      arterial wall when stents are irradiated with orthovoltage x-ray energies. This
      increase may explain the negative response in other studies. The presence of the
      stent does perturb the character and magnitude of the dose in the normal arterial
      wall as a function of beam quality.

PMID- 11229549
TI  - Brachytherapy for the interventional cardiologist and vascular surgeon.
AB  - PURPOSE: There has been recent interest in the use of brachytherapy for the
      possible prevention of restenosis after angioplasty. However, this field is
      unfamiliar to most interventional cardiologists. This article is meant to serve
      as an introduction to the principles of brachytherapy especially as it applies to
      intravascular brachytherapy. Because the intended audience is the interventional
      cardiologist, the details of physics, radiobiology, and radiation jargon has been
      kept at a minimum. METHODS: The main advantages of brachytherapy are that it can
      irradiate small volumes and conform to the target volume while sparing the
      surrounding normal tissues from the deleterious effects of irradiation. Various
      gamma- or beta-emitting radioisotopes can deliver the brachytherapy dose. In
      general, the beta emitters have fewer radiation exposure hazards, but the limited
      penetration of beta emitters can be a problem if deeper tissues need to be
      irradiated. Gamma sources can irradiate deeper but suffer from greater radiation
      exposure hazards. It should be remembered that the biological effects of
      radiation depend on a number of parameters, including the radiation modality,
      dose, dose rate, fractionation, treatment duration, dose prescription point, and
      the volume irradiated. The use of low energy isotopes, beta emitters, and remote
      controlled afterloading has reduced the radiation exposure to the medical
      caregivers. CONCLUSION: Intravascular brachytherapy is currently considered to be
      experimental. Those wishing to start a new intravascular brachytherapy program
      should comply with the required federal and state regulatory guidelines issued by
      the Nuclear Regulatory Commission, Food and Drug Administration, and their
      individual Institutional Review Board.

PMID- 11229550
TI  - Images in cardiovascular radiation medicine. Edge restenosis post gamma
      radiation.

PMID- 11229551
TI  - Circumventing the learning curve of dose and volume in intravascular
      brachytherapy.

PMID- 11229552
TI  - Basic principles and reasonable speculations in intravascular brachytherapy.

PMID- 11229553
TI  - Disproportionation and nuclease activity of bis[2-ethyl-2-hydroxybutanoato(2
      )]oxochromate(V) in neutral aqueous solutions.
AB  - Complex 1, [Cr(V)O(ehba)2]- (ehba = 2-ethyl-2-hydroxybutanoate(2-)) is the most
      studied model compound of relevance to the biological activity of Cr(V) with
      regard to Cr-induced cancers. The first detailed kinetic study of
      disproportionation of 1 under neutral pH conditions (pH 6.0-8.0, [NaClO4] = 1.0
      M, 37 degrees C) is reported. Kinetic data were collected by stopped-flow and
      conventional UV-vis spectroscopies and processed by the global analysis method.
      The disproportionation, which follows the stoichiometry 3Cr(V) --> 2Cr(VI) +
      Cr(III) (1), leads to release of 5 mol of H+/3 mol of Cr(V). Reaction 1 is
      accelerated by phosphate, but is not affected by acetate, HEPES, or Tris buffers.
      Initial rates of Cr(V) decay are directly proportional to [Cr(V)]0 (0.020-1.0
      mM); they increase with an increase in the pH values and decrease in the presence
      of a large excess of ehba ligand. The first direct evidence for the formation of
      Cr(IV) intermediates in reaction 1 has been obtained; however, their UV-vis
      spectral properties were different from those of the well-characterized Cr(IV)
      ehba complexes. The Cr(III) products of reaction I in phosphate buffers differ
      from those in the other buffers. A mechanism is proposed for reaction 1 on the
      basis of kinetic modeling. Influences of the reaction time and conditions on the
      extent of plasmid DNA cleavage induced by 1 have been studied under conditions
      corresponding to those of the kinetic studies. A comparison of the kinetic and
      DNA cleavage results has shown that direct interaction of 1 with the phosphate
      backbone of DNA is the most likely first step in the mechanism of DNA cleavage in
      neutral media. Small additions of Mn(II) ((0.01-0.1)[Cr(V)]0) did not affect the
      rate and stoichiometry of reaction 1, but suppressed the formation of Cr(IV)
      intermediates (presumably due to the catalysis of Cr(IV) disproportionation).
      However, much higher concentrations of Mn(II) ((0.1-1.0)[Cr(V)]0) were required
      to inhibit DNA cleavage induced by 1. Thus, contrary to previous reports (Sugden,
      K. D.; Wetterhahn, K. E. J. Am. Chem. Soc. 1996, 118, 10811-10818), inhibition by
      Mn(II) does not indicate a key role of Cr(IV) in Cr(V)-induced DNA cleavage.

PMID- 11229554
TI  - New alternating ferro- and antiferromagnetic one-dimensional complexes.
      Synthesis, characterization, crystal structure, and magnetic properties of.
AB  - The preparation, X-ray crystal structure, and magnetic properties of alternating
      1,1- and 1,3-azido-bridged copper(II) complex [Cu(4,4'-dmbpy)(N3)2]n (1, 4,4'
      dmbpy = 4,4'-dimethylbipyridine) have been reported. It crystallizes in triclinic
      system, space group P1, a = 7.9903(1) A, b = 9.3545(9) A, c = 10.754(2) A, alpha
      = 113.485(1) degrees, beta = 101.399(1) degrees, gamma = 101.897(1) degrees, Z =
      2. The magnetic properties of 1 have been investigated in the temperature range
      1.5-300 K. Alternating antiferromagnetic (-J = 191.0 cm(-1)) interaction through
      a 1,3-N3- bridge and ferromagnetic (J = 297.1 cm(-1)) interaction through a 1,1
      N3- bridge are obtained for 1 by analyzing the magnetic susceptibility data with
      the Hamiltonian H = -Jsigma(S2iS2i-1--alphaS2iS2i+1). It's derivatives ([Mn(4,4'
      dmbpy)(N3)2]n (2), [Ni(4,4'-dmbpy)(N3)2]n (3), and [Fe(4,4'-dmbpy)(N3)2]n (4) and
      the heterometallic derivatives [NiMn(4,4'-dmbpy)2(N3)4]n (5) and [CuMn(4,4'
      dmbpy)2(N3)4]n (6) have also been synthesized and characterized by electronic and
      IR spectra. The X-ray powder diffraction and the magnetic properties of 6 have
      also been discussed.

PMID- 11229555
TI  - Crystal supramolecular motifs: columns of embracing Ph3PMe+ or Ph3PCI+ cations
      controlling formation of.
AB  - The crystal structures of (Ph3PCl)2[Cu3Cl8] (1) (triclinic, space group P1, a =
      9.480(6) A, b = 10.243(8) A, c = 11.232(6) A, alpha = 86.76(4) degrees, beta =
      66.62(5) degrees, gamma = 83.92(4) degrees, Z = 1) and (Ph3PMe)2[Cu3Br8] (2)
      (triclinic, space group P1, a = 9.795(4) A, b = 10.472(4) A, c = 11.392(4) A,
      alpha = 86.67(3) degrees, beta = 66.67(3)degrees, gamma = 83.14(3) degrees, Z =
      1), reported here, demonstrate a new supramolecular motif for cations of the type
      Ph3PY+ where Y is CH3 or Cl. The crystals contain columns of cations propagated
      by alternating 6-fold phenyl embraces (6PE) and pseudo-6PE: the pseudo-6PE
      described here contains four phenyl rings and two hetero groups (Cl or CH3), and
      is symbolized as 4P2Y. The zigzag sequence of cations engaged in
      ...6P...4P2Y...6P...4P2Y... is similar to the zigzag chain of infinite 6-fold
      phenyl embraces (ZZI6PE) frequently adopted by Ph4P+ cations in crystals. One
      dimensionally nonmolecular anion chains with repeat unit [Cu3X8] run parallel to
      and between the columns of cations. The coordination geometry in the [Cu3X8(2-)]1
      to infinity chain has not been observed in crystals with other cations, and it is
      postulated that the attractive interactions between cations in the pseudo-ZZI6PE
      crystal supramolecular motif control the geometry of the anions through the
      requirement for commensurability of cation columns and anion chains.

PMID- 11229557
TI  - Heterometallic polymeric clusters containing tetraselenotungstate anion: one
      dimensional helical chain [[La(Me2SO)8.
AB  - [PPh4]2[WSe4] reacts with an equivalent of [Ag(MeCN)4][ClO4] in DMF to afford a
      linear polymeric cluster [[Ph4P][(mu-WSe4)Ag]]n (1). Treatment of cluster 1 with
      excess La(NO3)3.3H2O in Me2SO solution resulted in the formation of a helical
      chain polymeric cluster [[La(Me2SO)8][(mu-WSe4)3Ag3]]n (2). Cluster 2
      crystallizes in the monoclinic space group P2(1/n) with four formula units in a
      cell of dimensions a = 12.7642(5) A, b = 24.1725(9) A, c = 19.4012(7) A, and beta
      = 103.546(11) degrees. Refinement by full-matrix least-squares techniques gave
      final residuals R = 0.0540 and Rw = 0.1116 for 494 variables and 7593 reflections
      (Fo(2) > 2.0sigma(Fo(2))). The anion [[(mu-WSe4)3Ag3]]n(3n-) in 2 can be
      described as a butterfly-type SeWSe3Ag2 basic repeating unit linked through
      interactions with a Ag atom of one fragment and a Ag atom of another to form an
      intriguing helical array. The CuCN, KCN, and [Et4N]2[WSe4] reaction system
      resulted in the formation of a novel three-dimensional cluster [[Et4N]2[(mu4
      WSe4)Cu4(CN)4]]n (4) either in DMF/2-picoline or in solid at 80 degrees C.
      Cluster 4 crystallizes in the orthorhombic space group Fddd with cell constants a
      = 11.090(2) A, b = 23.206(5) A, c = 23.910(5) A, and Z = 8. Anisotropic
      refinement with 1510 reflections (Fo(2) > 2.0sigma(Fo(2))) and 82 parameters for
      all non-hydrogen atoms yielded the values of R = 0.0428 and Rw = 0.0887. The
      anion structure of 4 is built up from a WSe4Cu4 unit bridged by cyanide ligands
      to form a three-dimensional cross framework. The air- and moisture-stable
      polymeric clusters easily decompose into small molecular clusters when treated
      with ligands such as PPh3 and pyridine (Py). Cluster 2 exhibits both strong
      optical absorption and an optical self-focusing effect (effective alpha2 = 2.2 x
      10(-9) m2.W(-1), n2 = 6.8 x 10(-15) m2.W(-1); examined in a 0.13 mM DMF
      solution). Cluster 4 shows good photostability in the process of measurement and
      a large optical limiting effect (the limiting threshold is ca. 0.2 J.cm(-2)).

PMID- 11229556
TI  - Chemistry and insulin-mimetic properties of bis(acetylacetonate)oxovanadium(IV)
      and derivatives.
AB  - The syntheses and the solid state structural and spectroscopic solution
      characterizations of VO(Me-acac)2 and VO(Et-acac)2 (where Me-acac is 3-methyl-2,4
      pentanedionato and Et-acac is 3-ethyl-2,4-pentanedionato) have been conducted
      since both VO(acac)2 and VO(Et-acac)2 have long-term in vivo insulin-mimetic
      effects in streptozotocin-induced diabetic Wistar rats. X-ray structural
      characterizations of VO(Me-acac)2 and VO(Et-acac)2 show that both contain five
      coordinate vanadium similar to the parent VO(acac)2. The unit cells for VO(Et
      acac)2 and VO(Me-acac)2 are both triclinic, P1, with a = 9.29970(10) A, b =
      13.6117(2) A, c = 13.6642(2) A, alpha = 94.1770(10) degrees, beta = 106.4770(10)
      degrees, gamma = 106.6350(10) degrees for VO(Et-acac)2 and a = 7.72969(4) A, b =
      8.1856(5) A, c = 11.9029(6) A, alpha = 79.927(2) degrees, beta =
      73.988(2)degrees, gamma = 65.1790(10)degrees for VO(Me-acac)2. The total
      concentration of EPR-observable vanadium(IV) species for VO(acac)2 and
      derivatives in water solution at 20 degreesC was determined by double integration
      of the EPR spectra and apportioned between individual species on the basis of
      computer simulations of the spectra. Three species were observed, and the
      concentrations were found to be time, pH, temperature, and salt dependent. The
      three complexes are assigned as the trans-VO(acac)2.H2O adduct, cis-VO(acac)2.H2O
      adduct, and a hydrolysis product containing one vanadium atom and one R-acac-
      group. The reaction rate for conversion of species was slower for VO(acac)2 than
      for VO(malto)2, VO(Et-acac)2, and VO(Me-acac)2; however, in aqueous solution the
      rates for all of these species are slow compared to those of other vanadium
      species. The concentration of vanadium(V) species was determined by 51V NMR. The
      visible spectra were time dependent, consistent with the changes in species
      concentrations that were observed in the EPR and NMR spectra. EPR and visible
      spectroscopic studies of solutions prepared as for administration to diabetic
      rats documented both a salt effect on speciation and formation of a new halogen
      containing complex. Compound efficacy with respect to long-term lowering of
      plasma glucose levels in diabetic rats traces the concentration of the hydrolysis
      product in the administration solution.

PMID- 11229558
TI  - Ligand to ligand charge transfer in
      (hydrotris(pyrazolyl)borato)(triphenylarsine)copper(I).
AB  - Emission and UV-vis absorption spectra of
      (hydrotris(pyrazolyl)borato)(triphenylarsine)copper(I), (CuTpAsPh3),
      (hydrotris(pyrazolyl)borato)(triethylamine)copper(I), (CuTpNEt3), and
      (hydrotris(pyrazolyl)borato)(triphenylphosphine)copper(I), (CuTpPPh3), are
      reported. The spectra of the arsine complex contain low-energy bands (with a band
      maximum at 16,500 cm(-1) in emission and a weak shoulder centered at about 25,000
      cm(-1) in absorption) that are not present in the corresponding spectra of the
      amine or phosphine complexes. The lowest energy electronic transition is assigned
      to ligand to ligand charge transfer (LLCT) with some contribution from the metal.
      This assignment is consistent with PM3(tm) molecular orbital calculations that
      show the HOMO to consist primarily of pi orbitals on the Tp ligand (with some
      metal orbital character) and the LUMO to be primarily antibonding orbitals on the
      AsPh3 ligand (also with some metal orbital character). The absorption shoulder
      shows a strong negative solvatochromism, indicative of a reversal or rotation of
      electric dipole upon excitation, and consistent with a LLCT. The trends in the
      energies of the electronic transitions and the role of the metal on the LLCT are
      discussed.

PMID- 11229559
TI  - In-situ gas-phase luminescence and time-of-flight mass spectroscopic detection of
      photofragments during photochemical synthesis of copper particles from bis(tert
      butylacetoacetato)copper.
AB  - During the 308 nm laser-driven photochemical synthesis of Cu particles from
      bis(tert-butylacetoacetato)copper, gas-phase photogenerated intermediates are
      identified by luminescence and time-of-flight mass spectroscopies. Pure Cu
      deposits are obtained as homogeneous, granular 200 nm particles. In the gas
      phase, luminescent photoproducts are observed and atomic Cu, Cu2, and dissociated
      ligand are identified spectroscopically. In addition, mass spectroscopy
      identifies Cu atoms, the dissociated ligand, a monoligated complex, and fragments
      of the ligands. The implications of the photofragmentation that produces copper
      atoms and dimers for the laser-assisted production of the Cu deposits are
      discussed.

PMID- 11229560
TI  - Vibronic coupling in dicyano-complex-bridged mixed-valence complexes. Relaxation
      of vibronic constraints in systems with degenerate bridging-ligand and electron
      transfer excited states.
AB  - Intense near-infrared (NIR) absorption bands have been found in mixed-valence
      Ru(NH3)5(2+,3+) complexes bridged by trans-Ru(py)4(CN)2 and cis-Os(bpy)2(CN)2,
      epsilonmax approximately 1.5 x 10(3) cm(-1) and deltav1/2 approximately 5 x 10(3)
      cm(-1) for bands at 1,000 and 1,300 nm, respectively. The NIR transitions
      implicate substantial comproportionation constants (64 and 175, respectively)
      characteristic of moderately strong electronic coupling in the mixed-valence
      complexes. This stands in contrast to the weakly forbidden electronic coupling of
      Ru(NH3)5(2+,3+) couples bridged by M(MCL)(CN)2+ complexes (MCL = a
      tetraazamacrocyclic ligand) (Macatangay; et al. J. Phys. Chem. 1998, 102, 7537).
      A straightforward perturbation theory argument is used to account for this
      contrasting behavior. The electronic coupling between a cyanide-bridged, donor
      acceptor pair, D-(CN-)-A, alters the properties of the bridging ligand. Such
      systems are described by a "vibronic" model in which the electronic matrix
      element, HDA, is a function of the nuclear coordinates, QN, of the bridging
      ligand: HDA = HDA degrees + bQN. Electronic coupling in the dicyano-complex
      bridged, D-[(NC)M(CN)]-A, systems is treated as the consequence of the
      perturbational mixing of the "local", D(NC)M and M(CN)A, vibronic interactions.
      If M is an electron-transfer acceptor, then the nuclear coordinates are assumed
      to be configured so that bQN is larger for D(NC)M but very small (bQN
      approximately 0) for M(CN)A. When the vertical energies of the corresponding
      charge-transfer transitions, EDM and EDA, differ significantly, a perturbation
      theory treatment results in HDA = HDAHAM/Eave independent of M and consistent
      with the earlier report. When EDM approximately equals EDA, configurational
      mixing of the excited states leads to HDA proportional to HDM, consistent with
      the relatively intense intervalence bands reported in this paper. Some
      implications of the model are discussed.

PMID- 11229561
TI  - Platinum diimine bis(acetylide) complexes: synthesis, characterization, and
      luminescence properties.
AB  - A new set of luminescent platinum(II) diimine complexes has been synthesized and
      characterized. The anionic ligands in these complexes are arylacetylides. The
      complexes are brightly emissive in fluid solution with relative emission quantum
      yields phiem ranging from 3 x 10(-3) to 10(-1). Two series of complexes have been
      investigated. The first has the formula Pt(Rphen)(C...CC6H5)2 where Rphen is 1,10
      phenanthroline substituted in the 5-position with R = H, Me, Cl, Br, NO2, or
      C...CC6H5, while the second has the formula Pt(dbbpy)(C=CC6H4X)2 where dbbpy =
      4,4'-di(tert-butyl)bipyridine and X = H, Me, F, or NO2. From NMR, IR, and
      electronic spectroscopies, all of the complexes are assigned a square planar
      coordination geometry with cis-alkynyl ligands. The crystal structure of
      Pt(phen)(Ce-CC6H4CH3)2 confirms this assignment. All of the complexes exhibit an
      absorption band at ca. 400 nm that corresponds to a Pt d-->pi*diimine charge
      transfer transition. The variation of lambdamax for this band with substituent
      variation supports this assignment. From similar changes in the energy of the
      solution luminescence as a function of substituents R and X, the emissive excited
      state is also of MLCT origin, but with spin-forbidden character on the basis of
      excited-state lifetime measurements (0.01-5.6 micros). The complexes undergo
      electron-transfer quenching, showing good Stern-Volmer behavior using 10
      methylphenothiazine and N,N,N',N'-tetramethylbenzidine as reductive quenchers.
      Excited-state reduction potentials are estimated on the basis of a simple
      thermochemical analysis. Crystal data for Pt(phen)(C...CC6H4CH3)2: monoclinic,
      space group C2/c, a = 19.0961(1) A, b = 10.4498(1) A, c = 11.8124(2) A, beta =
      108.413(1) degrees, V = 2236.49 A3, number of reflections 1614, number of
      variables 150, R1 = 0.0163, wR2 (I > 2sigma) = 0.0410.

PMID- 11229562
TI  - Synthesis and magnetic and transport properties of Sr6V9S22O2: "AM2S5" phases
      revisited.
AB  - The compound Sr6V9S22O2 was prepared from SrS, sulfur, vanadium metal, and V2O5
      at 950 degrees C in an evacuated quartz tube. The compound is rhombohedral, R3,
      with a = 8.7538(6) A, c = 34.934(3) A, and Z = 3, and shows strong preferred
      orientation in its XRD profiles (00l) due to the layered nature of the structure.
      The compound contains charged CdI2 type VS2 layers of formula [V7S14]4- separated
      by [Sr6(VOS3)2(S2)]4+ layers. The latter has VOS3(3-) tetrahedra and S2(2-)
      disulfide units linked by Sr2+ ions. Magnetic susceptibility and four-probe
      resistivity studies show essentially temperature-independent paramagnetism above
      80 K and small gap semiconductor behavior, respectively. The compound has a
      positive Hall coefficient at room temperature. The relationship among Sr6V9S22O2,
      "SrV2S5" (J. Solid State Chem. 1996, 126, 189), and other AM2S5 phases is
      discussed.

PMID- 11229563
TI  - Synthesis and characterization of new 19-vertex macropolyhedral boron hydrides.
AB  - The new boron hydride anions 10-R-B19H19- (R = H, Thx) were synthesized by the
      reaction of M2[B18H20] (M = Na, K) with HBRCl.SMe2 (R = H, Thx) or HBCl2.SMe2 in
      diethyl ether. The anions are comprised of edge-sharing, nido 10- and 11-vertex
      cluster fragments, and are characterized by their 11B, 11B[1H], and 11B-11B COSY
      NMR spectra. The salt [(Ph3P)2N][B19H20].0.5THF crystallized in the triclinic
      space group P1 (a = 12.6344-(2) A, b = 13.5978(2) A, c = 14.1401(2) A; alpha =
      77.402(2) degrees, beta = 81.351(2) degrees, gamma = 73.253(2) degrees). Possible
      synthetic pathways are discussed. The dianion B19H19(2-) is formed by
      deprotonation of B19H20- with Proton Sponge (1,8-bis(dimethylamino)naphthalene)
      in THF, and is identified on the basis of its 11B, 11B[1H], and 11B-11B COSY NMR
      spectra.

PMID- 11229564
TI  - Time-resolved electron spin resonance of gallium and germanium porphyrins in the
      excited triplet state.
AB  - Gallium and germanium porphyrin complexes in the lowest excited triplet (T1)
      state have been studied by time-resolved electron spin resonance (TRESR). It is
      found that for Ge(TPP)(OH)2 (TPP = dianion of tetraphenylporphyrin) intersystem
      crossing (ISC) from the lowest excited singlet (S1) state to the T1x and T1y
      sublevels is faster than that to the T1z sublevel (T1x, T1y, and T1z are
      sublevels of the T1 state), while the ISC of ZnTPP and Ga(TPP)(OH) is selective
      to the T1z sublevel. This is interpreted by a weak interaction between the dpi
      orbital of germanium and LUMO (eg) of the porphyrin ligand, resulting in small
      spin-orbit coupling (SOC). The interpretation is supported by molecular orbital
      calculations. The ISC of Ge(OEP)(OH)2 (OEP = dianion of octaethylporphyrin) and
      Ge(Pc)(OH)2 (Pc = dianion of tetra-tert-butylphthalocyanine) is found to be
      selective to the T1z sublevel in contrast to Ge(TPP)(OH)2. This dependence on the
      porphyrin ligand is reasonably explained by a difference between the 3(a(1u)eg)
      (the OEP and Pc complexes) and 3(a(2u)eg) (the TPP complex) configurations. This
      is the first observation of a difference in selective ISC between the 3(a(1u)eg)
      and 3(a(2u)eg) configurations. The TRESR spectrum of Ge(TPP)Br2 is different from
      those of Ge(TPP)Cl2 and Ge(TPP)(OH)2, and is interpreted by SOC between the T1
      and T2 states. From ESR parameters the square of the coefficient of the eg
      orbital on bromine is evaluated as 0.018 in the T1 state.

PMID- 11229566
TI  - Heterobimetallics of nickel-iron dinitrosyl: electronic control by chelate and
      diatomic ligands.
AB  - Reaction of [PPN][Fe(NO)2(SePh)2] (1) with dimeric [Ni(mu-SCH2CH2SCH2CH2S)]2 in
      the presence of additional NO2- produced the neutral heterobimetallic [(ON)Ni[(mu
      SCH2CH2)2S]Fe(NO)2] complex (2). The X-ray crystal structures of 1 and 2 show
      distorted tetrahedral iron dinitrosyl groups, assigned according to the Feltham
      Enemark notation as [Fe(NO)2]9 The Fe-NO bonds are off linearity by an average of
      approximately equals 10 degrees for compounds 1 and 2, while a more linear Ni-NO
      coordination with a Ni-NO distance of 1.644(2) A was found in 2. The v(NO) value
      of complex 2 is consistent with an assignment for [Ni(NO)]9 of Ni0(NO)+ as is
      known for analogous phosphine derivatives, P3Ni0(NO)+. EPR signals of g values =
      2.02-2.03 confirmed the existence of the odd electron in the chalcogenated
      [Fe(NO)2]9 compounds. Two [Fe(NO)2]10 complexes coordinated by the nickel(II)
      dithiolate, (bismercaptoethanediazacyclooctane)nickel(II), (Ni-1), (Ni
      1)Fe(CO)(NO)2 and (Ni-1)Fe(NO)2, were prepared for comparison to the Ni0(NO)+
      derivative and other monomeric and homodimetallic derivatives of the Fe(NO)2
      fragment. While the oxidation level of Fe(NO)2 is the primary determinant of
      v(NO) values, they are also highly sensitive to ancillary ligands and, thereby,
      the distal metal influence through the bridging thiolate donor.

PMID- 11229567
TI  - Picosecond dynamics of photoinduced interligand electron transfer in
      [Re(MQ+)(CO)3(dmb)]2+ (dmb = 4,4 dimethyl-2,2 bipyridine, MQ+ = N-methyl-4,4
      bipyridinium).
AB  - Excited-state dynamics of [Re(MQ+)(CO)3(dmb)]2+, (dmb = 4,4'-dimethyl-2,2'
      bipyridine, MQ+ = N-methyl-4,4'-bipyridinium) was studied by femtosecond time
      resolved spectroscopy in the visible spectral region. Excitation at 400 or 330 nm
      prepares a mixture of Re --> dmb and Re --> MQ+ metal-to-ligand charge-transfer,
      MLCT, states. The Re --> dmb MLCT state undergoes a dmb*- --> MQ+ interligand
      electron transfer to produce a relatively long-lived Re --> MQ+ MLCT excited
      state, which was characterized spectroscopically. The lifetime of this reaction
      was determined as 8.3 ps in CH3CN. The interligand electron transfer occurs as a
      nonadiabatic process in the Marcus normal region. The electronic coupling was
      estimated to lie in the range 20-40 cm(-1). The electron transfer becomes
      partially adiabatic in ethylene glycol solutions for which the reaction lifetime
      of 14.0 ps was determined. Depending on the medium relaxation time, the principal
      control of the electron-transfer rate changes from electron tunneling to solvent
      relaxation.

PMID- 11229568
TI  - Magnetic exchange in [Mn2(mu-O)3(tmtacn)2]2+: metal-metal bonding or
      superexchange?
AB  - A computational study of the tris-mu-oxo-bridged manganese dimer [Mn2(mu
      O)3(NH3)6]2+ as a model for [Mn2(mu-O)3(tmtacn)2]2+ (tmtacn = N',N",N"'-trimethyl
      1,4,7-triazacyclononane) has been undertaken to investigate the magnetic coupling
      in this complex. Although the complex has a very short Mn--Mn distance, 2.3 A,
      and a large antiferromagnetic exchange constant, 2Jab = -780 cm(-1), the
      calculations reveal that the magnetic coupling is dominated by superexchange via
      the mu-oxo bridges and that direct Mn-Mn interaction is small.

PMID- 11229569
TI  - Homotrinuclear lanthanide(III) arrays: assembly of and conversion from
      mononuclear and dinuclear units.
AB  - The reactions of potentially hexadentate H2bbpen (N,N'-bis(2-hydroxybenzyl)-N,N'
      bis(2-pyridylmethyl)-ethylenediamine, H2L1), H2(Cl)bbpen (N,N'-bis(5-chloro-2
      hydroxybenzyl)-N,N'-bis(2-pyridylmethyl)ethylenediamine, H2L2), and H2(Br)bbpen
      (N,N'-bis(5-bromo-2-hydroxybenzyl)-N,N'-bis(2-pyridylmethyl)ethylenediamine,
      H2L3) with Ln(III) ions in the presence of a base in methanol resulted in three
      types of complexes: neutral mononuclear ([LnL(NO3)]), monocationic dinuclear
      ([Ln2L2(NO3)]+), and monocationic trinuclear ([Ln3L2(X)n(CH3OH)]+), where X =
      bridging (CH3COO-) and bidentate ligands (NO3-, CH3COO-, ClO4-) and n is 4. The
      formation of a complex depends on the base (hydroxide or acetate) and the size of
      the respective Ln(III) ion. All complexes were characterized by infrared
      spectroscopy, mass spectrometry, and elemental analyses; in some cases, X-ray
      diffraction studies were also performed. The structures of the neutral
      mononuclear [Yb(L1)(NO3)], dinuclear [Pr2(L1)2(NO3)(H2O)]NO3.CH3OH and
      [Gd2(L1)2(NO3)]NO3.CH3OH.3H2O, and trinuclear
      [Gd3(L3)2(CH3COO)4(CH3OH)]ClO4.5CH3OH and
      [Sm3(L1)2(CH3COO)2(NO3)2(CH3OH)]NO3.CH3OH.3.65H2O were solved by X-ray
      crystallography. The [LnL(NO3)] or [Ln2L2(NO3)]+ complexes could be converted to
      [Ln3L2(X)n(CH3OH)]+ complexes by the addition of 1 equiv of a Ln(III) salt and 2
      3 equiv of sodium acetate in methanol. The trinuclear complexes were found to be
      the most stable of the three types, which was evident from the presence of the
      intact monocationic high molecular weight parent peaks ([Ln3L2(X)n]+) in the mass
      spectra of all the trinuclear complexes and from the ease of conversion from the
      mononuclear or dinuclear to the trinuclear species. The incompatibility of the
      ligand denticity with the coordination requirements of the Ln(III) ions was
      proven to be a useful tool in the construction of multinuclear Ln(III) metal ion
      arrays.

PMID- 11229570
TI  - Coaggregation of paramagnetic d- and f-block metal ions with a podand-framework
      amine phenol ligand.
AB  - This report covers initial studies in the coaggregation of nickel (Ni2+) and
      lanthanide (Ln3+) metal ions to form complexes with interesting structural and
      magnetic properties. The tripodal amine phenol ligand H3tam (1,1,1-tris(((2
      hydroxybenzyl)amino)methyl)ethane) is shown to be particularly accommodating with
      respect to the geometric constraints of both transition and lanthanide metal
      ions, forming isolable complexes with both of these ion types. In the solid-state
      structure of [Ni(H2tam)(CH3CN)]PF6.2.5CH3CN.0.5CH3OH (1), the Ni(II) center has a
      distorted octahedral geometry, with an N3O2 donor set from the [H2tam]- ligand
      and a coordinated solvent (acetonitrile) occupying the sixth site. The reaction
      of stoichiometric amounts of H3tam with the Ni(II) ion in the presence of
      lanthanide(III) ions provides [LnNi2(tam)2]+ cationic complexes which contain
      coaggregated metal ions. These complexes are isolable and have been characterized
      by a variety of analytical techniques, with mass spectrometry proving to be
      particularly diagnostic. The solid-state structures of
      [LaNi2(tam)2(CH3OH)1/2(CH3CH2OH)1/2(H2O)]ClO4.0.5CH3OH.0.5CH3CH2OH.4H2O (2),
      [DyNi2(tam)2(CH3OH)(H2O)]ClO4.CH3OH. H2O(6), and
      [YbNi2(tam)2(H2O)]ClO4.2.58H2O(9) have been determined. Each complex contains two
      octahedral Ni(II) ions, each of which is encapsulated by the ligand tam3- in an
      N3O3 coordination sphere; each [Ni(tam)]-unit caps the lanthanide(III) ion via
      bridging phenoxy oxygen donor atoms. In 2, La3+ is eight-coordinated, while in 6,
      Dy(III) is seven- (to "weakly eight-") coordinated, and Yb(III) in 9 has a six
      coordination environment. The complexes are symmetrically different, 2 possessing
      C2 symmetry and 6 and 9 having C1 symmetry. Magnetic studies of 2, 6, and 9
      indicate that antiferromagnetic exchange coupling between the Ni(II) and Ln(III)
      ions increases with decreasing ionic radius of Ln(III).

PMID- 11229572
TI  - Analogues for the molybdenum center of sulfite oxidase: oxomolybdenum(V)
      complexes with three thiolate sulfur donor atoms.
AB  - cis,trans-(L-N2S2)Mo(V)O(SR) [L-N2S2H2 = N,N'-dimethyl-N,N'
      bis(mercaptophenyl)ethylenediamine; R = CH2Ph, CH2CH3, and p-C6H4-Y (Y = CF3, Cl,
      Br, F, H, CH3, CH2CH3, and OCH3)] are the first structurally characterized
      mononuclear Mo compounds with three thiolate donors, as occurs at the Mo active
      site in sulfite oxidase. X-ray crystal structures of the cis,trans-(L
      N2S2)Mo(V)O(SR) compounds, where R = CH2Ph, CH2CH3, p-C6H4-OCH3, and p-C6H4-CF3,
      show a similar coordination geometry about the Mo atom with all three sulfur
      thiolate donors in the equatorial plane. This coordination geometry places two
      adjacent S ppi orbitals parallel to the Mo=O bond, analogous to the orientation
      in the ene-dithiolate ligand in sulfite oxidase; the third S ppi orbital lies in
      the equatorial plane. Charge-transfer transitions from the S p to the Mo d
      orbitals occur at approximately 28,000 cm(-1) (epsilon: 4,400-6,900 L mol(-1)]
      cm(-1)) and 15,500 cm(-1) (epsilon: 3,200-4,900 L mol(-1) cm(-1)). The EPR
      parameters are nearly identical for all the cis,trans-(L-N2S2)Mo(V)O(SR)
      compounds (g1 approximately 2.022, g2 approximately 1.963, g3 approximately
      1.956, Al approximately 58.4 x 10(-4) cm(-1), A2 approximately 23.7 x 10(-4) cm(
      1), A3 approximately 22.3 x 10(-4) cm(-1)) and are typical of an oxo-Mo(V) center
      coordinated by multiple thiolate donors. The g and A tensors are related by a 24
      degrees rotation about the coincident g2 and A2 tensor elements, reflecting the
      approximate Cs coordination symmetry. These EPR parameters more closely mimic
      those of the low pH form of sulfite oxidase and the "very rapid" species of
      xanthine oxidase than previous model compounds with two or four thiolate donors.
      The cis,trans-(L-N2S2)Mo(V)O(SR) compounds undergo a quasi-reversible, one
      electron reduction and an irreversible oxidation that show a linear dependence
      upon the Hammett parameter, sigmap, of the Y group. The cis,trans-(L
      N2S2)Mo(V)O(SR) compounds provide a well-defined platform for the systematic
      investigation of the electronic structures of the Mo(V)OS3 centers and their
      implications for molybdoenzymes.

PMID- 11229573
TI  - Electronic effects in transition metal porphyrins. 10. Effect of ortho
      substituents on the temperature dependence of the NMR spectra of a series of spin
      admixed perchloratoiron(III) tetrakis(2,6- or 2,4,6-phenyl
      substituted)porphyrinates.
AB  - The perchloratoiron(III) complexes of a series of 2,6-disubstituted
      tetraphenylporphyrin ligands, where the 2,6-phenyl substituents were -H, -F, -Cl,
      -Br, or -OMe, as well as two 2,4,6-phenyl-substituted complexes, where the
      substituents were -Me and -OMe, have been investigated as a function of
      temperature by 1H NMR spectroscopy. Curvature in the 1/T dependence was evident
      in most cases. Forced linear extrapolation of the temperature dependence observed
      over the range of the study yielded Curie plots that include negative slopes with
      very large positive 1/T intercepts (Cl approximately Br > Me > H) to negative
      slope with near zero intercept (tri-OMe) to positive slope with very large
      negative intercept (F, di-OMe). The NMR results were combined with EPR
      spectroscopic data and curve-fitting procedures based on an expanded Curie law to
      arrive at a consistent overview of the variety of temperature-dependence
      behaviors observed. This overview relies upon the premise that, in addition to
      the ground state observed by EPR spectroscopy, one (or more) thermally accessible
      excited state(s) are populated to varying degrees over the temperature range of
      the NMR measurements. If only one excited state is considered, the analysis is
      consistent with the ground state being a largely intermediate-spin state (S =
      3/2) for the majority of the complexes but a largely high-spin state (S = 5/2)
      for ((2,6-F2)4TPP)FeOClO3 and ((2,6-(OMe)2)4TPP)FeOClO3.

PMID- 11229574
TI  - Wavelength-dependent photochemistry in Cr(CNPh)6: a study of photosubstitution
      and photoinduced electron transfer using time-resolved spectroscopy.
AB  - The wavelength dependence of photosubstitution, photoinduced electron transfer,
      and the time-resolved spectra of Cr(CNPh)6, a compound having low-lying MLCT
      states, were investigated. Photosubstitution quantum yields increase with
      increasing excitation energy while photoinduced electron transfer quantum yields
      decrease with increasing excitation energy. At the lowest excitation energy used
      (532 nm, or 18,800 cm(-1)), the quantum yields for both electron transfer and
      photosubstitution reach the same maximum value, 0.29. Picosecond time-resolved
      absorption spectra at 355 and 532 nm excitation wavelengths show two features: a
      bleach signal centered at 400 nm and an excited state absorption (ESA) in the 600
      nm region. The ESA signal is much weaker for 532 nm excitations than for 355 nm
      excitations. Following a 355 nm flash, the bleach and ESA decay exponentially
      with the same lifetime of 23 micros. This implies a simple ligand dissociation
      followed by recombination. Bleach recovery kinetics after a 532 nm flash are more
      complicated: two or three exponential components are required to fit the data.
      Cr(CNPh)6 exhibits two photochemical mechanisms: at high excitation energy, a
      simple charge neutral dissociation occurs; at low energy, it is proposed that a
      phenylisocyanide radical anion dissociates, forming a radical pair that is
      responsible for the observed substitution and electron transfer reactivity, and
      the complicated nanosecond kinetics. The primary processes for both reactions
      occur in less than 20 ps.

PMID- 11229575
TI  - The elusive structures of pentakis[(triphenylphosphine)gold]ammonium(2+) bi.
AB  - [Pentakis[(triphenylphosphine)gold(I)]ammonium(2+)] bis[(tetrafluoroborate)(1-)]
      was prepared from [tetrakis[(triphenylphosphine)gold(I)]-ammonium(1+)]
      [tetrafluoroborate(1-)] and [(triphenylphosphine)gold(I)] tetrafluoroborate in
      hexamethyl phosphoric triamide and tetrahydrofuran at 20 degrees C in 53% yield
      and crystallized from dichloromethane as the new solvate [[(Ph3P)Au]5N]3 [BF4]6
      [CH2Cl2]4. The crystal structure of this product has been determined by single
      crystal X-ray methods [monoclinic, P2(1/n), a = 34.200(3), b = 15.285(1), c =
      53.127(3) A, beta = 107.262(2) degrees, V = 26521(3) A3, Z = 12, at 153 K]. The
      lattice contains three independent trinuclear dications that have no
      crystallographically imposed symmetry and are mutually similar in their molecular
      structure. The geometry of the [Au5N] core with pentacoordinate nitrogen atoms is
      intermediate between trigonal-bipyramidal and square pyramidal with severe
      distortions to minimize the Au-Au distances along some of the edges of the
      polyhedra. The three structures are thus different from that found previously in
      the tetrahydrofuran solvate [[(Ph3P)-Au]5N](BF4)2(C4H8O)2, where the geometry of
      the same trinuclear dication is closer to the trigonal-bipyramidal reference
      model. The new results are discussed in the light of the structures of
      tetra(gold)ammonium cations in salts of the type [[(Ph3P)Au]4N]+X- and of related
      tetra-, penta-, and hexacoordinate poly(gold)phosphonium, -arsonium, -sulfonium,
      and -selenonium cations.

PMID- 11229576
TI  - Reduced zirconium halide clusters in aqueous solution.
AB  - Reduced hexazirconium halide cluster compounds have good solubility and stability
      in strongly acidic and/or halide-rich aqueous solutions. Cyclic voltammetric (CV)
      measurements in aqueous media established that [(Zr6BCl12)(H2O)6]2+/+ and
      [(Zr6BBr12)(H2O)6]2+/+ exhibited positive half-wave potentials (E1/2 = 0.059V and
      0.160 V, respectively) vs the SHE, indicating that these clusters are only
      modestly reducing. Several new crystalline cluster compounds have been isolated
      from cold 12 M HCl solutions; the structures of each contain extended hydrogen
      bonding water networks. Crystallographic data for these compounds are reported as
      follows: [Rb0.44(H3O)4.56][(Zr6BCl12)Cl6].19.44H2O (3), cubic, Im3m, a =
      13.8962(3) A, Z = 2; (H3O)5[(Zr6BeCl12)Cl6].19H2O (4), cubic, Im3m, a =
      13.8956(4) A, Z = 2; (H3O)5[(Zr6MnCl12)Cl6].19H2O (5), cubic, Im3m, a = 14.029(3)
      A, Z = 2; (H3O)4[(Zr6BCl12)Cl6].12.97H2O (6), tetragonal, P4(2)/mnm, a =
      11.5373(2) A, c = 15.7169(4) A, Z = 2; (H3O)4[(Zr6BCl2)Br6].13.13H2O (7),
      tetragonal, P4(2)/mnm, a = 11.7288(6) A, c = 15.931(1) A, Z = 2.

PMID- 11229577
TI  - Coordination chemistry of verdazyl radicals: group 12 metal (Zn, Cd, Hg)
      complexes of 1,4,5,6-tetrahydro-2,4-dimethyl-6-(2 pyridiyl)-1,2,4,5-tetrazin 
      3(2H)-one (pvdH3) and 1,5-dimethyl-3-(2 pyridil)-6-oxoverdazyl (pvd).
AB  - Ferricyanide oxidation of 1,4,5,6-tetrahydro-2,4-dimethyl-6-(2'-pyridyl)-1,2,4,5
      tetrazin-3(2H)-one (pvdH3) produces the stable chelating free radical 1,5
      dimethyl-3-(2'-pyridyl)-6-oxoverdazyl (pvd) as an orange solid. Combination of
      group 12 metal halides with the ligand pvdH3 in acetonitrile results in
      precipitation of metal complexes. The mercuric chloride complex crystallizes in
      the monoclinic space group P2(1/c) with unit cell dimensions a = 8.5768(8) A, b =
      19.1718(17) A, c = 8.5956(8) A, beta = 90.405 degrees, and V = 1413.4(2) A3. The
      mercuric ion is tricoordinate with a distorted trigonal planar geometry. Cadmium
      iodide and zinc chloride induce ring opening of the tetrazine resulting in
      pentacoordinate complexes of a hydrazone ligand. The cadmium iodide complex
      crystallizes in the triclinic space group P1 with cell dimensions a = 7.7184(8)
      A, b = 8.0240(9) A, c = 13.348(2) A, alpha = 97.876(4) degrees, beta = 95.594(6)
      degrees, gamma = 107.304(6) degrees, and V = 773.40(21) A3. Oxidation of all
      three metal complexes produces verdazyl radicals. Metal coordination is indicated
      by small changes in the EPR spectrum and by changes in the UV-visible spectrum,
      in particular the changes in the position of bands in the visible region. The
      metal halide-pvd complexes can also be synthesized by direct combination of metal
      halides with the free radical.

PMID- 11229578
TI  - A new type of hexaosmium boride cluster, H3Os6(CO)16B, that does not conform to
      electron counting rules.
AB  - A new type of hexaosmium boride cluster, H3Os6(CO)16B, was produced in the
      thermolysis of H3Os3(CO)9(BCO). This complex is an 86 valence electron cluster,
      but the Os6 framework does not possess one of the geometries previously observed
      for Os6 clusters that have 86 valence electrons. [HOs6(CO)18]- and [Os6(CO)18]2-
      have octahedral frameworks while that of H2Os6(CO)18 is a face-capped square
      pyramid. The Os6 framework of H3Os6(CO)16B can be viewed as being derived from a
      pentagonal bipyramid that is missing one equatorial vertex. It contains an
      interior boron atom. Alternatively, it can be viewed like the 84 valence cluster
      Os6(CO)18 as either a bicapped tetrahedron, with a boron atom residing on the
      edge of the tetrahedron that is common to the capped faces, or a face-capped
      trigonal bipyramid, with the boron atom on an equatorial edge of the bipyramid
      that is also an edge of the capped face. H3Os6(CO)16B was characterized by 1H,
      and 11B, 13C NMR, IR, and mass spectroscopies and single-crystal X-ray
      diffraction analysis. The molecular structure was determined from two separate
      crystals. The analysis of each crystal yielded virtually identical structures,
      but their volumes differed by 36 A3 due to differences in packing in the unit
      cell. Data for crystal I of H3Os6(CO)16B: monoclinic P2(1/n), a = 9.954(2) A, b =
      15.780(4) A, c = 16.448(3) A, beta = 91.07(1) degrees, Z = 4. Data for crystal II
      of H3Os6(CO)16B: monoclinic P2(1/n), a = 9.927(2) A, beta = 16.623(2) A, b =
      16.0233(10) A, beta = 97.78(1) degrees, Z = 4.

PMID- 11229579
TI  - Binding properties of octaaminocryptands.
AB  - Complexation and protonation equilibria were studied in aqueous solution for a
      new range of aminocryptand ligands, N(CH2CH2NHCH2RCH2NHCH2CH2)3N, (R = m-xylyl, p
      xylyl, 2,5-furan, 2,6-pyridine) and demonstrate that stability constants for
      first transition series ions Co2+ to Zn2+ are relatively high. X-ray
      crystallography shows that the cryptands are reasonably well preorganized for
      complexation. The furan-spaced cryptand L6.H2O crystallizes in the rhomobohedral
      space group R3 (no. 148) with a = 14.645(1), b = 14.645(1), and c = 25.530(4) A,
      whereas the m-xylyl-spaced cryptand L4 crystallizes in the triclinic space group
      P1 (no. 2) with a = 9.517(1), b = 15.584(2), and c = 23.617(4) A. The highest
      formation constant (log beta21 = 33.07) is observed for the dicopper cryptate of
      a pyridine-spaced cryptand, suggesting involvement in complexation of donors from
      the spacer link. This pyridine-spaced host also shows good selectivity for
      copper(II) over zinc(II), making it a possible candidate for treatment of copper
      excess pathology.

PMID- 11229580
TI  - Molecular structure of an Fe(IV) species:.
AB  - The molecular structure of the formal iron(IV) porphyrinate derivative,
      [[Fe(TTP)]2N]SbCl6 (TTP = tetratolylporphyrinate), is reported. The structural
      parameters are compared to the previously reported species [Fe(TPP)]2N, in which
      the iron oxidation state is +3.5. Both the equatorial and axial bond distances in
      [[Fe(TTP)]2N]SbCl6 are slightly shortened and consistent with an increased formal
      charge on iron. The value for the axial Fe-N distance is 1.6280(7) A, and the
      average value of the equatorial Fe-Np distances is 1.979(5) A. The Mossbauer
      isomer shift decreases upon oxidation, again consistent with an increase in
      formal charge. Values for the isomer shift at room temperature are -0.13 mm/s for
      [[Fe(TTP)]2N]SbCl6 and 0.04 mm/s for [Fe(TTP)]2N. Crystal data for
      [[Fe(TTP)]2N]SbCl6 are as follows: orthorhombic, space group Fddd, Z = 8, a =
      23.689(2) A, b = 31.056(3) A, c = 22.7788(18) A.

PMID- 11229581
TI  - Bidentate ligands that contain pyrrole in place of pyridine.
AB  - A series of ligands are prepared that are analogues of benzo-fused derivatives of
      2,2'-bipyridine (bpy), in which pyrrole has been substituted for a pyridine ring.
      These ligands include 2-(2'-pyridyl)-indole, 2-(2'-pyrrolyl)-quinoline, and
      pyrrolo[3,2-h]quinoline. A novel reductive cyclization approach to the latter
      species is presented. All these ligands react with [Ru(bpy-d8)2Cl2], undergoing
      cyclometalation with concurrent deprotonation, to form complexes of the type
      [Ru(L)(bpy-d8)2]+ where L binds as a monoanionic ligand. The complexes are
      readily characterized by their 1H NMR spectra. Changes in the redox potentials
      and the electronic absorption spectra of both the ligands and the complexes are
      interpreted in terms of charge delocalization on the ligand.

PMID- 11229582
TI  - Assignment of multiline tungsten-183 NMR spectra of diamagnetic polyoxotungstates
      from intensity patterns.
AB  - Measurement of relative integrated intensities and peak heights of multiline one
      dimensional 183W NMR spectra of diamagnetic polyoxotungstates can result in
      complete or partial assignment of chemical shifts, even when 183W-183W spin
      coupled satellites are not detectable or well-resolved. The intensity of the
      center peak of each signal is diminished according to the number and type (corner
      vs edge-sharing of WO6 octahedra) of potential spin-couplings. Application of
      the method is exemplified by analysis of spectra of alpha-[XW11O39]n- and
      derivatives, alpha2-[P2W17O61]10-, and [As4W40O140]28-. Intensity patterns of the
      six-line spectra of the beta1 and beta3 isomers of [XW11O39]n- are sufficiently
      different to allow identification.

PMID- 11229583
TI  - Coordination chemistry of trivalent lanthanide and actinide ions in dilute and
      concentrated chloride solutions.
AB  - We have used EXAFS spectroscopy to investigate the inner sphere coordination of
      trivalent lanthanide (Ln) and actinide (An) ions in aqueous solutions as a
      function of increasing chloride concentration. At low chloride concentration, the
      hydration numbers and corresponding Ln,An-O bond lengths are as follows: La3+, N
      = 9.2, R = 2.54 A; Ce3+, N = 9.3, R = 2.52 A; Nd3+, N = 9.5, R = 2.49 A; Eu3+, N
      = 9.3, R = 2.43 A; Yb3+, N = 8.7, R = 2.32 A; Y3+, N = 9.7, R = 2.36 A; Am3+, N =
      10.3, R = 2.48 A; Cm3+, N = 10.2, R = 2.45 A. In ca. 14 M LiCl, the early Ln3+
      ions (La, Ce, Nd, and Eu) show inner sphere Cl- complexation along with a loss of
      H2O. The average chloride coordination numbers and Ln-Cl bond lengths are as
      follows: La3+, N = 2.1, R = 2.92 A; Ce3+, N = 1.8, R = 2.89 A; Nd3+, N = 1.9, R =
      2.85 A; Eu3+, N = 1.1, R = 2.81 A. The extent of Cl- ion complexation decreases
      going across the Ln3+ series to the point where Yb3+ shows no Cl- complexation
      and no loss of coordinated water molecules. The actinide ions, Am3+ and Cm3+,
      show the same structural effects as the early Ln3+ ions, i.e., Cl- ion
      replacement of the H2O at high chloride thermodynamic activities. The Clion
      coordination numbers and An-Cl bond lengths are: Am3+, N = 1.8, R = 2.81 A; Cm3+,
      N = 2.4, R = 2.76 A. When combined with results reported previously for Pu3+
      which showed no significant chloride complexation in 12 M LiCl, these results
      suggest that the extent of chloride complexation is increasing across the An3+
      series. The origin of the differences in chloride complex formation between the
      Ln3+ and An3+ ions and the relevance to earlier work is discussed.

PMID- 11229584
TI  - Gold(I) heteroatom-substituted imido complexes. Amino nitrene loss from.
AB  - The heteroatom-substituted imido complexes [(LAu)3(mu-NX)]+ (X = NR2, R = Ph, Me,
      Bz; X = OH, Cl; L = a phosphine) have been prepared from the reactions of NH2X
      with [(LAu)3(mu-O)]+. Thermally unstable [(LAu)3(mu-NNMe2)]+ (L = P(p-XC6H4)3, X
      = H, F, Me, Cl, MeO) decompose to the gold cluster [LAu]6(2+) and
      tetramethyltetrazene Me2NN=NNMe2. The decomposition is first-order overall with a
      rate constant that increases with increasing pKa of the phosphine ligand.
      Activation parameters for the decomposition are deltaH(not equal to) = 99(4)
      kJ/mol and deltaS(not equal to) = 18.5(5) J/K.mol for L = PPh3 and deltaH(not
      equal to) = 78(3) kJ/mol and deltaS(not equal to) = -47(2) J/K.mol for L = P(p
      MeOC6H4)3. The decomposition of analogous [(LAu)3(mu-NNBz2)]+ produces bibenzyl,
      indicative of the release of free amino nitrene Bz2NN.

PMID- 11229585
TI  - Mixed chloride/amine complexes of dimolybdenum(II,II). 6. Stepwise substitution
      of amines by tertiary phosphines and vice versa: stereochemical hysteresis.
AB  - The substitution reactions of primary amines by tertiary phosphines in quadruply
      bonded dimolybdenum(II,II) complexes Mo2Cl4(NH2R)4 have been studied. The
      exchange reaction has been shown to result at room temperature in disubstituted
      species Mo2Cl4(NH2R)2(PR3)2 (PR3 = PMe3, NH2R = NH2Prn (1a), NH2But (2a), NH2Cy
      (3a); PR3 = PMe2Ph, NH2R = NH2Cy (4a)), while heating is needed to obtain fully
      substituted complexes Mo2Cl4(PR3)4. The crystal structure of disubstituted
      products has been investigated by X-ray crystallography and revealed that they
      all belong to the alpha-isomer, having both phosphine groups at the same Mo atom.
      Crystal data are as follows: for 1a, tetragonal space group I4(1/a) with a =
      17.737(2) A, c = 15.6915(6) A, and Z = 8; for 3a, monoclinic space group P2(1)
      with a = 10.963(3) A, b = 10.117(2) A, c = 13.323(4) A, beta = 90.05(2) degrees,
      and Z = 2; for 4a, triclinic space group P1 with a = 9.329(3) A, b = 10.206(2) A,
      c = 18.975(3) A, alpha = 85.45(2) degrees, beta = 87.10(1) degrees, gamma =
      80.88(1) degrees, and Z = 2. The substitution processes for the direct and
      reverse reactions have been monitored by 31P NMR. They both proceed in a stepwise
      manner; however, a stereochemical hysteresis is taking place, i.e., the back
      reaction, the substitution of phosphines by amines, goes through another isomer
      of Mo2Cl4(NH2R)2(PR3)2, having phosphine ligands on different Mo atoms. This beta
      isomer is more thermodynamically stable and can be obtained by thermal conversion
      of the alpha-form. All chemical equilibria studied in the paper have been
      explained as governed by a higher trans effect of PR3 groups compared to NH2R
      groups.

PMID- 11229586
TI  - Redox-tunable valence tautomerism in a cobalt Schiff base complex.

PMID- 11229588
TI  - Polyoxometalate-diphosphate complexes. 5. Cigar-shaped 30
      molybdobispyrophosphate: structure of (N(C4H9)4)2H.

PMID- 11229587
TI  - Synthesis and characterization of a novel tetranuclear copper(II) resor.

PMID- 11229589
TI  - Polyoxometalate-diphosphate complexes. 6. Possible intermediates in the molybdate
      catalyzed hydrolysis of pyrophosphate: structure of hexamolybdopyrophosphate.

PMID- 11229590
TI  - Establishment of Colossoma brachypomum embryo cell line.

PMID- 11229591
TI  - Immortalization of mammary cells from estrogen receptor alpha knock-out and wild
      type mice.

PMID- 11229592
TI  - Adenovirus-mediated expression of tissue plasminogen activator does not alter
      endothelial cell proliferation and invasion.

PMID- 11229593
TI  - Establishment and characteristics of a human signet ring cell gastric carcinoma
      cell line (SJ-89) under serum-free conditions.

PMID- 11229594
TI  - Whey: a by-product for eucaryotic cell cryopreservation.

PMID- 11229595
TI  - Cyclic strain induces proliferation of cultured embryonic heart cells.
AB  - Embryonic heart cells undergo cyclic strain as the developing heart circulates
      blood to the embryo. Cyclic strain may have an important regulatory role in
      formation of the adult structure. This study examines the feasibility of a
      computerized cell-stretching device for applying strain to embryonic cardiocytes
      to allow measurement of the cellular response. A primary coculture of myocytes
      and a secondary culture of nonmyocytes from stage-31 (7 d) embryonic chick hearts
      were grown on collagen-coated membranes that were subsequently strained at 2 Hz
      to 20% maximal radial strain. After 24 h, total cell number increased by 37+/-6%
      in myocyte cocultures and by 26+/-6% in nonmyocyte cultures over unstrained
      controls. Lactate dehydrogenase and apoptosis assays showed no significant
      differences in cell viabilities between strained and unstrained cells. After 2 h
      strain, bromodeoxyuridine incorporation was 38+/-1.2% versus 19+/-0.2% (P < 0.01)
      in strained versus unstrained myocyte cocultures, and 35+/-2.1% versus 16+/-0.2%
      (P = 0.01) in nonmyocyte cultures. MF20 antibody labeling and periodic acid
      Schiff (PAS) staining estimated the number of myocytes in strained wells as 50
      67% larger than in control wells. Tyrosine phosphorylation may play a role in the
      cellular response to strain, as Western blot analysis showed an increase in
      tyrosine phosphorylation of two proteins with approximate molecular weights of 63
      and 150 kDa within 2 min of strain. The results of this study indicate that
      embryonic chick cardiocytes can be cultured in an active mechanical environment
      without significant detachment and damage and that increased proliferation may be
      a primary response to strain.

PMID- 11229596
TI  - Demonstration of estrogen receptors and of estrogen responsiveness in the HKT
      1097 cell line derived from diethylstilbestrol-induced kidney tumors.
AB  - This study was undertaken in order to examine the estrogen sensitivity of HKT
      1097, an established cell line recently derived from diethylstilbestrol (DES)
      induced kidney tumors in Syrian hamsters. Estrogen receptor (ER) level in HKT
      1097, determined by enzyme-linked immunoassay, was 67 fmol/mg protein, i.e., a
      value approx. 30% lower than that found in Syrian hamster kidney tumors. ER
      immunostaining in cells fixed with Carnoy's mixture, as well as ER demonstration
      by Western blotting, suggested DES-induced nuclear translocation or stabilization
      of the receptor within the nucleus. Kinetic parameters of estrogen binding to ER
      in HKT-1097 cells were 8.4 x 10(-11) M and 60.8 fmol/mg protein for Kd and Bmax,
      respectively. The Kd of estrogen binding to ER in HKT-1097 was close to that
      evaluated for the receptor in breast cancer-derived MCF-7 cell line, whereas the
      Bmax value was approx. seven times lower in HKT-1097 as compared to MCF-7. In HKT
      1097 cells, antiestrogens ICI 182,780 and RU 58,668 induced ER downregulation and
      competed with estrogen binding to the receptor. As demonstrated by Western blot
      analysis, DES exposure led to an increased expression of progesterone receptor
      (PgR) in HKT-1097 cells. Addition of DES to estrogen-free medium produced a
      stimulation of growth in both HKT-1097 and MCF-7 cells, but the mitogenic effect
      was less marked for HKT-1097. Despite the fact that ICI 182,780 and RU 58,668
      clearly interact with HKT-1097 cell ER, they appeared unable to suppress DES
      induced stimulation of growth and increase of PgR expression.

PMID- 11229597
TI  - Isolation, immortalization, and initial characterization of uterine cell lines:
      an in vitro model system for the porcine uterus.
AB  - The aim of this study was to develop immortalized cell lines from porcine uterus.
      Endometrial cells including luminal epithelium (LE), glandular epithelium (GE),
      stroma (ST), and myometrium (MYO) were enzymatically isolated from the uterus of
      a day 12 pregnant gilt. Primary cultures were immortalized by transduction with a
      retroviral vector containing the E6 and E7 open reading frames of human
      papillomavirus type 16 (LXSN-16E6E7) packaged by the amphotropic fibroblast line
      PA-317. Cells having integrated the vector were selected by resistance to the
      neomycin analog G418 (0.4-1.5 mg/ml). Surviving cells were maintained in complete
      culture medium containing G418 (0.1 mg/ml) and subcultured for 1 yr. Expression
      of the E7 protein was confirmed in all cell lines by Western blotting. Phase
      contrast microscopy revealed that LE and GE cells exhibited cobblestone
      morphology, whereas ST and MYO cells exhibited spindle-shaped morphology. The
      epithelial origin of LE and GE was confirmed by positive immunostaining for
      cytokeratin. Stromal and MYO cells were vimentin-positive, but cytokeratin
      negative. The MYO cell lines were positive for smooth muscle alpha-actin
      staining, whereas LE, GE, and ST cell lines were negative for alpha-actin.
      Western blotting indicated that all cell lines expressed both estrogen and
      progesterone receptors, but only GE cells secreted uteroferrin (UF).
      Collectively, these porcine uterine cell lines provide an in vitro model for
      studying cell type-specific actions of hormones and cytokines, signal
      transduction pathways, cell-cell interactions, and gene expression.

PMID- 11229598
TI  - Estrogen stimulation of ovarian surface epithelial cell proliferation.
AB  - Ovarian cancer is the leading cause of gynecological cancer mortality, and 85-90%
      of this malignancy originates from the ovarian surface epithelium (OSE). The
      etiology of ovarian epithelial cancer is unknown, but a role for estrogens has
      been suspected. However, the effect of estrogens on OSE cell proliferation
      remains to be determined. Using the rabbit model, our studies have demonstrated
      that 17beta-estradiol stimulates OSE cell proliferation and the formation of a
      papillary ovarian surface morphology similar to that seen in human ovarian serous
      neoplasms of low malignant potential. Immunohistochemical staining of ovarian
      tissue sections with an antibody to the estrogen receptor alpha demonstrates its
      expression in both OSE cells and stromal interstitial cells. In primary ovarian
      cell cultures, the proliferative response of the epithelial cells to 17beta
      estradiol depends on the expression of the estrogen receptor alpha in the
      epithelial cells. However, when the epithelial cells are grown together with
      ovarian stromal cells, their proliferative response to this hormone is greatly
      enhanced, suggesting the involvement of stromal-epithelial interactions. These
      studies suggest a role for estrogens and the estrogen receptor alpha in OSE
      growth.

PMID- 11229600
TI  - Focal adhesions: structure and dynamics.
AB  - Interactions of cells with the extracellular matrix are essential for the control
      of tissue remodelling, cell migration, and embryogenesis. At the cell
      extracellular matrix contact points, specialized structures are formed and termed
      focal adhesions, where transmembrane adhesion receptors provide a structural link
      between the actin cytoskeleton and the extracellular matrix components. Numerous
      structural and regulatory proteins assemble at the cytoplasmic face of focal
      adhesions in a Rho-dependent fashion.

PMID- 11229601
TI  - Golvesin-GFP fusions as distinct markers for Golgi and post-Golgi vesicles in
      Dictyostelium cells.
AB  - Golvesin is a new protein associated with membranes of the Golgi apparatus and
      post-Golgi vesicles in Dictyostelium cells. An internal hydrophobic sequence of
      24 amino-acid residues is responsible for anchoring golvesin to the membranes of
      these organelles. In an attempt to visualize organelle dynamics in vivo, we have
      used specific antibody and other labels to localize golvesin-green fluorescent
      protein (GFP) constructs to different cellular compartments. With a GFP tag at
      its N-terminus, golvesin shows the same localization as the untagged protein. It
      is transferred to two post-Golgi compartments, the endosomal and contractile
      vacuole systems. Endosomes are decorated with GFP-golvesin within less than 10
      min of their internalisation, and keep the label during the acidic phase of the
      pathway. Blockage of the C-terminus with GFP causes entrapment of the protein in
      the Golgi apparatus, indicating that a free C-terminus is required for transfer
      of golvesin to any of the post-Golgi compartments. The C-terminally tagged
      golvesin proved to be a reliable Golgi marker in Dictyostelium cells revealing
      protrusion of Golgi tubules at peak velocities of 3 to 4 microm x s(-1). The
      fusion protein is retained in Golgi vesicles during mitosis, visualizing Golgi
      disassembly and reorganization in line with cytokinesis.

PMID- 11229599
TI  - Expression of epidermal growth factor and platelet-derived growth factor
      receptors during cervical carcinogenesis.
AB  - Altered expression of epidermal growth factor receptor (EGFR) is common in a
      variety of epithelial malignancies, including cervical cancer. However, the
      prognostic significance of EGFR expression is controversial for cervical cancer.
      Platelet-derived growth factor receptor (PDGFR) expression status is unknown in
      cervical cancer. Our results demonstrated that expression of EGFR and PDGFR was
      greatly enhanced in vivo and in organotypic cultures of low-grade cervical
      dysplastic tissues, but levels were decreased in high-grade lesions. To our
      knowledge, this is the first report identifying the expression of PDGFR in human
      epithelium. When low-grade dysplastic organotypic culture tissues were induced to
      differentiate more completely, EGFR expression, but not PDGFR expression, was
      relocalized to the basal layer as seen in normal tissues. Differentiation also
      induced phosphorylation of EGFR but not PDGFR. Our results suggest a role for
      EGFR and PDGFR during the early stages of cervical carcinogenesis, and
      demonstrate the facility of organotypic cultures to study the role of these
      growth factors in the development of cervical cancer.

PMID- 11229602
TI  - Respective roles of protein tyrosine kinases and protein kinases C in the
      upregulation of beta-catenin distribution, and compaction in mouse
      preimplantation embryos: a pharmacological approach.
AB  - The cellular distribution of beta-catenin was determined by western blotting and
      laser confocal scanning microscopy in both control and pharmacologically
      manipulated mouse preimplantation embryos. Most of the stored maternal beta
      catenin is Triton X-100-extractable and distributed throughout the cytoplasm. In
      2-cell stage embryos, the remaining molecules are concentrated in regions of cell
      contact and, to a lesser extent, at non apposed surfaces. Association of beta
      catenin with the cortex of non apposed membranes decreases as cleavage proceeds,
      and is lost at compaction. In contrast to the rapid cross-linking of cell
      surfaces induced by wheat germ agglutinin, the diacylglyceride-induced compaction
      like adhesion of 2- and 4-cell embryos correlates with complete restriction of
      beta-catenin to the apposing membranes. On the contrary, tyrphostin B46, a
      specific protein tyrosine kinase inhibitor, fails to induce both premature beta
      catenin relocalisation and compaction. In addition, we show that orthovanadate
      induces a dramatic increase in the level of phosphotyrosine labelling of cell
      cell junctions in compacted 8-cell stage embryos without inducing their
      decompaction. However, most of these orthovanadate tyrosine-phosphorylated
      proteins are detergent-soluble, while beta-catenin restricted to the apposing
      membranes is not. In conclusion, our results confirm that diacylglycerol
      dependent kinases upregulate both beta-catenin redistribution and compaction, and
      indicate that neither tyrosine kinases, nor tyrosine phosphatases are critical
      for the proper onset of compaction which seems, in addition, not causally linked
      to tyrosine dephosphorylation of beta-catenin.

PMID- 11229603
TI  - Fibre-type distribution and subcellular localisation of alpha and beta enolase in
      mouse striated muscle.
AB  - Enolase is a dimeric glycolytic enzyme exhibiting tissue specific isoforms.
      During ontogenesis, a transition occurs from the embryonic alphaalpha towards the
      specific alphabeta, and betabeta isoforms in striated muscle. Immunocytochemical
      analyses on transverse sections of adult mouse gastrocnemius muscle, allowed us
      to compare the expression of alpha and beta subunits to that of myosin heavy
      chain (MHC) isoforms. Levels of beta immunoreactivity followed the order IIB >
      IIX > IIA > I. This gradient parallels the ATPase activity associated to MHC
      isoforms, indicating that the expression of beta enolase in myofibres is finely
      regulated as a function of energetic requirements. By contrast, variations in
      alpha immunolabelling intensity appeared independent of fibre types. Longitudinal
      muscle sections exhibited a striated pattern of alpha immunoreactivity. Confocal
      microscopy analyses demonstrated that alpha was localised at the M band. Most
      beta immunoreactivity was diffuse all over the sarcoplasm. However, some beta
      immunoreactivity was striated and localized at both Z and M bands. Thus, betabeta
      enolase could participate to multi-enzyme complexes present at the I band, and
      involved with local ATP production. Our results support the notion that isozymes
      differ in their ability to interact with other macromolecules, thus segregating
      to different subcellular sites where they would respond to specific functional
      demands.

PMID- 11229604
TI  - A novel approach to studying the migratory morphology of embryonic mesenchymal
      cells.
AB  - A polarized morphology, defined by extension of an anterior pseudopod, is
      essential for the amoeboid migration of embryonic mesenchymal cells. Leukocytes
      adopt a similar morphology immediately following suspension in simple buffers
      containing chemotactic factors. Polarization in suspension therefore provides a
      rapid and sensitive screening assay for putative regulators of leukocyte
      migration. The aim of the present study was to investigate whether this assay
      might also be used to study the motile behaviour of embryonic mesenchymal cells.
      Primary cultures of mesenchymal cells were established from explants of stage 28
      chick embryo corneal-limbal stroma. Serum-starved, subconfluent cultures were
      harvested using ethylene-diamine tetra-acetic acid and resuspended in Hanks'
      solution for up to 15 min at 37 degrees C. A variety of cell shapes, including
      spherical cells, blebbed cells, and cells with either non-polarized or polarized
      pseudopodia were observed. The proportions of cells with pseudopodia increased
      significantly over time. Treatment of cells with the chemotactic mitogen platelet
      derived growth factor-BB (PDGF-BB, homodimer isoform) suppressed blebbing and
      increased both pseudopod formation and polarization. Optimal polarization
      occurred in concentrations of PDGF-BB that are similar to those required for
      optimal chemotaxis (10 ng x mL(-1)). The polarization observed in the absence of
      PDGF-BB suggests that the migration of cells examined in this study might be
      controlled at least in part by some intrinsic mechanism. In addition, the strong
      polarization response to PDGF-BB confirms the role for this growth factor during
      corneal development. Observations of mesenchymal cell morphology in suspension,
      therefore provide novel data regarding the motile behaviour of embryonic cells.

PMID- 11229605
TI  - Differentiation of mucous neck cells into parietal cells: a new concept of
      mitochondrial biogenesis.
AB  - Parietal cells of the gastric fundic mucosa are small and contain only a few tiny
      mitochondria when they begin to differentiate from mucous neck cells. The
      canalicular ATPase activity characteristic of mature parietal cells is discrete
      in these young cells, whereas areas of very high activity are apparent in the
      Golgi complex, reticulum, nuclear envelope, mitochondrial wall, and plasma
      membrane. Close relations and contacts occur between mitochondria and these
      organelles, and the size and number of mitochondria increase progressively. These
      relations, as well as mitochondrial ATPase activity (a true differentiation
      marker), cease once the mitochondria become as numerous and large as those of a
      mature parietal cell. Our observations suggest that a secondary form of
      mitochondrial biogenesis, involving the massive participation of other organelles
      and independent of the classical mechanisms inherent in mitosis, occurs in
      parietal cells at the beginning of G1 phase during the 6 days of their
      maturation.

PMID- 11229606
TI  - Effects of conventional and new peritoneal dialysis solutions on human peritoneal
      mesothelial cell viability and proliferation.
AB  - OBJECTIVE: To investigate the biocompatibility of "new" peritoneal dialysis (PD)
      solutions with bicarbonate/lactate buffer, non glucose osmotic agents (icodextrin
      or amino acids), neutral pH, and low levels of glucose degradation products
      (GDPs). DESIGN: Using M199 culture medium as a control, we compared conventional
      and new PD solutions with respect to their effects on the viability of human
      peritoneal mesothelial cells (HPMCs) [using lactate dehydrogenase (LDH) release],
      on DNA damage in HPMCs [using single-cell gel electrophoresis (Comet assay)], and
      on HPMC proliferation (using [3H]-thymidine incorporation). The experiments were
      performed after cell growth was synchronized by incubation with serum-free media
      for 24 hours. The PD solutions tested included commercial 1.5% glucose and 4.25%
      glucose solutions with 40 mmol/L lactate (D 1.5 and D 4.25, respectively), 7.5%
      icodextrin (E), 1.1% amino acid (N), 1.5% glucose solution in a triple-chambered
      bag (Bio 1.5), 1.5% glucose solution in a dual-chambered bag with neutral pH (Bal
      1.5), and 1.5% glucose and 4.25% glucose solution containing 25 mmol/L
      bicarbonate and 15 mmol/L lactate (P 1.5 and P 4.25, respectively). RESULTS: When
      HPMCs were continuously exposed to undiluted PD solutions, D 1.5, D 4.25, P 4.25,
      and E increased LDH release by more than 60% at 24 hours. All PD solutions tested
      increased LDH release by more than 75% at 96 hours. With 2-fold diluted PD
      solutions, only D 4.25 significantly increased LDH release at 96 hours, though
      not at 24 hours. When cells were exposed to undiluted PD solutions for 60 min and
      allowed to recover in M199 for up to 96 hours, LDH release was significantly
      higher at 24-96 hours in E (55%-69%) and D 1.5 (48%-72%) as compared with control
      [M199 (18%)]. Release of LDH was significantly lower with PD solutions containing
      lower levels of GDPs than those in D 1.5, suggesting that GDPs may have a role in
      cell viability. The D solutions (D 1.5 and D 4.25) and E solution also induced
      significant DNA damage. Both LDH release and DNA damage by D and E were
      significantly attenuated by adjusting the solution pH to 7.4, suggesting that low
      pH may be implicated in PD solution-induced DNA damage and cell death. When
      diluted 2-fold, D 1.5, D 4.25, and P 4.25 decreased [3H]-thymidine incorporation
      to 43%, 34%, and 41% of control, respectively, at 24 hours and to 45%, 26%, and
      35% of control, respectively, at 96 hours. When cells were exposed to undiluted
      PD solutions for 5 minutes and allowed to recover in M199 for up to 96 hours,
      D1.5 and P 4.25--but not D 4.25--significantly inhibited cell proliferation at 24
      hours. This effect was sustained up to 96 hours. CONCLUSIONS: The present in
      vitro data demonstrate that PD solutions with low pH, or high levels of GDPs, or
      both, promote HPMC death and DNA damage, and that PD solutions with high
      osmolality inhibit cell proliferation. Solutions with neutral pH, amino acids,
      and "low GDPs" appear to be more biocompatible than conventional PD solutions.
      These results require confirmation in in vivo animal and clinical studies.

PMID- 11229607
TI  - Glucose degradation products and the peritoneal mesothelium.
AB  - Conventional heat-sterilized, glucose-based peritoneal dialysis (PD) fluids
      contain significant amounts of glucose degradation products (GDPs) such as
      aldehydes and dicarbonyl compounds (glyoxal, methylglyoxal). These GDPs have been
      shown to impair cell functions in various in vitro experimental models. In
      peritoneal mesothelial cells, GDPs dose-dependently inhibit cell proliferation
      and mediator synthesis. In addition, some GDPs potently promote generation of
      advanced glycation end-products (AGEs). Immunohistochemistry finds AGEs in the
      peritoneal membrane of chronic continuous ambulatory peritoneal dialysis (CAPD)
      patients, suggesting that peritoneal AGE accumulation may be involved in chronic
      peritoneal fibrosis. The formation of GDPs might be prevented by filter
      sterilization of PD fluids. Another option is to separate the glucose and the
      buffer system in dual-chambered or multi-chambered containers. In these systems,
      the glucose is kept in a separate compartment at high concentration and very low
      pH-both conditions being known to minimize the degree of glucose decomposition
      during autoclaving. Initial experimental evidence suggests that these novel,
      multi-chambered fluids significantly improve in vitro biocompatibility; however,
      the clinical relevance of these results remains to be established in clinical
      trials.

PMID- 11229608
TI  - Biological significance of reducing glucose degradation products in peritoneal
      dialysis fluids.
AB  - Carbohydrates are not stable when exposed to energy; they degrade into new
      molecules. In peritoneal dialysis (PD) fluids, degradation of glucose occurs
      during the heat sterilization procedure. The biological consequences of this
      degradation are side effects such as impaired proliferation and impaired host
      defense mechanisms, demonstrated in vitro for a great variety of cells. Several
      highly toxic compounds--such as formaldehyde and 3-deoxyglucosone--have been
      identified in PD fluids. Carbonyl compounds, apart from being cytotoxic, are also
      well-known promoters of irreversible advanced glycation end-products (AGEs),
      which might participate in the long-term remodeling of the peritoneal membrane.
      Various approaches can be used to reduce the formation of glucose degradation
      products (GDPs) during heat sterilization. Some examples are shortening the
      sterilization time, lowering the pH, removing catalyzing substances, and
      increasing glucose concentration. The latter three factors are employed in the
      multi-compartment bag with a separate chamber containing pure glucose at high
      concentration and low pH. Gambrosol trio, a PD fluid produced in this way, shows
      reduced cytotoxicity, normalized host defense reactions, less AGE formation, and
      reduced concentrations of formaldehyde and 3-deoxyglucosone. Moreover, in the
      clinical situation, the fluid turns out to be more biocompatible for the patient,
      causing less mesothelial cell damage, which in the long term could lead to a more
      intact peritoneal membrane. CONCLUSION: Glucose degradation products in heat
      sterilized fluids for peritoneal dialysis are cytotoxic, promote AGE formation,
      and cause negative side effects for the patient. Using improved and well
      controlled manufacturing processes, it is possible to produce sterile PD fluids
      with glucose as the osmotic agent but without the negative side effects related
      to GDPs.

PMID- 11229609
TI  - First in vitro and in vivo experiences with Stay-Safe Balance, a pH-neutral
      solution in a dual-chambered bag.
AB  - In addition to low pH and high osmolarity, glucose degradation products (GDPs)
      are considered to play a major role in the bioincompatibility of peritoneal
      dialysis fluids (PDFs). The formation of GDPs can be reduced by separating the
      glucose component of the solution (kept at very low pH) from the lactate
      component of the solution (kept at alkaline pH) during sterilization and storage.
      This development has been achieved by the use of a dual-chambered bag.
      Immediately before infusion, the seam between the two chambers is opened, and the
      contents are mixed. The result is a fluid with a more physiologic pH in the range
      6.8 - 7.4. Concentrations of 3-deoxyglucosone (3-DG), methylglyoxal (MG),
      acetaldehyde (AA), and formaldehyde (FA) in Stay-Safe Balance (Fresenius Medical
      Care, Bad Homburg, Germany) were remarkably reduced when compared to conventional
      PD solution [conventional PDF (1.5% glucose): 172 micromol/L, 6 microLmol/L, 152
      micromol/L, and 7 micromol/L respectively; Stay-Safe Balance (1.5% glucose): 42
      micromolL, < 1 micromol/L, < 2 micromol/L, and < 3 micromol/L respectively;
      conventional PDF (4.25% glucose): 324 micromol/L, 10 micromol/L, 182 micromol/L,
      and 13 micromol/L respectively; Stay-Safe Balance (4.25% glucose): 60 micromol/L,
      < 1 micromol/L, < 2 micromol/L, and < 3 micromol/L respectively). Human
      peritoneal mesothelial cells (HPMCs) were exposed to a control solution, a
      conventional PDF [CAPD 2, 1.5% glucose (Fresenius Medical Care, Bad Homburg,
      Germany)], and Stay-Safe Balance, either in a co-incubation model (24-hour PDF
      exposure) or in a pre-incubation model (30-min PDF exposure), followed by 24-hour
      recovery in culture medium. Interleukin-1beta (IL-1beta)-stimulated (1 ng/mL) IL
      6 secretion from HPMCs was assessed by ELISA. Exposure of HPMCs to conventional
      PDF resulted in a significant reduction in IL-6 release, which was fully restored
      following exposure to Stay-Safe Balance. In addition to the short-term
      investigations, long-term in vitro studies were also carried out. All fluids had
      near-neutral pH and were changed every second day. After 1, 3, 5, 7, 10, and 13
      days of exposure, cell viability was assessed. Whereas exposure to conventional
      PDF resulted in a significant reduction in HPMC viability after just 3 - 5 days,
      no significant toxicity of filter-sterilized or dual-chambered fluid was observed
      for up to 13 days. An observational study with 9 patients suggested that the
      efficacy of Stay-Safe Balance is equivalent to that of conventional solution.
      However, even short-term treatment (8+/-1 weeks) with this more biocompatible
      solution seems to improve mesothelial cell mass as indicated by a rise in cancer
      antigen 125 (CA125) from a baseline of 47+/-37 U/min to 172+/-90 U/min. Our data
      indicate that Stay-Safe Balance may help to better preserve peritoneal membrane
      cell function. An ongoing European multicenter study is expected to confirm these
      results.

PMID- 11229610
TI  - Effects of bicarbonate/lactate solution on peritoneal advanced glycosylation end
      product accumulation.
AB  - Advanced glycosylation end-products (AGEs) are associated with diabetic
      complications and peritoneal damage after long-term peritoneal dialysis (PD) with
      high glucose dialysis solutions. Glucose degradation products (GDPs) derived
      during heat sterilization of high glucose dialysis solutions are thought to
      accelerate AGE formation. A new technique of separating glucose from electrolytes
      has yielded markedly lower GDP levels and permitted the use of dialysis solutions
      containing the physiologic buffer bicarbonate. Formation of AGEs in vitro with
      this new solution is significantly lower compared with formation of AGEs with
      conventional solutions. The purpose of the present study was to investigate the
      effect of long-term intraperitoneal use of new, neutral dialysis solution (B/L)
      containing bicarbonate (25 mmol/L) and lactate (15 mmol/L) on peritoneal AGE
      accumulation and permeability. Normal male Sprague-Dawley rats were used. Twice
      daily for 12 weeks, 30 mL of new solution (B/L) or conventional solution [Lac
      (lactate 40 mmol/L)] was injected into the peritoneal cavity of the test rats. As
      a control, rats that were not injected were kept for 12 weeks in the same manner
      as the test rats. After 12 weeks, a 2-hour peritoneal equilibration test (PET)
      was performed in the test rats. After the PET, the parietal peritoneum and liver
      were obtained for evaluation of peritoneal morphology and for
      immunohistochemistry for AGE. Intensity of AGE staining was semi-quantitatively
      graded from 0 to 3. The omentum was also obtained and immediately frozen for
      analysis of pentosidine content by high-performance liquid chromatography.
      Compared with findings in the control group, hematoxylin and eosin staining of
      the parietal peritoneum and liver samples revealed partial denudation of
      mesothelial cells in the Lac group; denudation was not remarkable in the B/L
      group. The B/L solution showed significantly less AGE staining in the peritoneal
      cavity compared to conventional solution. However, B/L solution failed to lower
      pentosidine levels. Intraperitoneal volume and the ratio of dialysate glucose at
      2 hours to dialysate glucose at instillation (D2/D0 glucose) were significantly
      lower and the ratio of dialysate urea to plasma urea at 2 hours (D2/P2 urea) was
      significantly higher in the Lac and B/L groups than in the control group.
      Intraperitoneal volume was significantly higher in the B/L group than in the Lac
      group; D2/D glucose and D2P2 urea did not differ between the two groups. In
      conclusion, peritoneal ultrafiltration decreased after long-term PD. The B/L
      solution showed a small but statistically significant protective effect against
      decreasing ultrafiltration as compared with Lac solution. The B/L solution
      attenuated peritoneal AGE accumulation compared with conventional solution, but
      did not affect peritoneal pentosidine levels. These findings indicate that
      biochemical kinetics of various AGE peptides are not unique, but multivalent.

PMID- 11229611
TI  - Peritoneal accumulation of advanced glycosylation end-products in diabetic rats
      on dialysis with icodextrin.
AB  - OBJECTIVE: To evaluate and compare the effects of glucose-based solutions to
      those of icodextrin with respect to peritoneal transport characteristics and
      formation of advanced glycosylation end-products (AGEs) in the peritoneal
      membrane in the diabetic rat model of peritoneal dialysis (PD). STUDY DESIGN:
      Thirty-three male Sprague-Dawley rats weighing between 275 - 300 g were divided
      into 5 groups: group C (n = 6), control rats with catheter but not dialyzed;
      group D (n = 5), diabetic rats with catheter but not dialyzed; group G (n = 7),
      diabetic rats dialyzed with standard 2.5% glucose solution for daytime exchanges
      and 4.25% glucose solution for the overnight exchange; group H (n = 8), diabetic
      rats dialyzed with standard 2.5% glucose solution for daytime exchanges and 7.5%
      icodextrin solution for overnight exchanges; group I (n = 7), diabetic rats
      dialyzed with 7.5% icodextrin solution for all exchanges. Dialysis exchanges were
      performed three times daily with an instillation volume of 25 mL per exchange for
      a period of 12 weeks. Tissue sections were stained using a monoclonal anti-AGE
      antibody. One-hour peritoneal equilibration tests (PET) were performed every 4
      weeks for comparison of transport characteristics. RESULTS: The level of
      immunostaining was lowest in group C and highest in group G. Significant
      differences were seen between group C and groups G, H, and I (p < 0.001, p =
      0.001, and p< 0.05 respectively). Significant differences were also found between
      group G and groups D and I (p < 0.05 and p < 0.05 respectively). Over time,
      glucose concentration at the end of an exchange versus concentration at
      instillation (D/D0 glucose) decreased and dialysate-to-plasma ratio (D/P) of urea
      increased. Significant differences were found between groups C and H for D/D0
      glucose (0.40+/-0.01 vs 0.35+/-0.01, p < 0.05); and between groups C and H for
      D/P urea (0.87+/-0.03 vs 0.97+/-0.02, p < 0.05). CONCLUSIONS: These results
      suggest that AGE formation is lower with the use of peritoneal dialysis solution
      containing icodextrin than with glucose-based solutions. We conclude that the use
      of icodextrin may be helpful in slowing the deterioration of the peritoneal
      membrane, prolonging its use for dialysis.

PMID- 11229613
TI  - Pre-clinical biocompatibility testing of peritoneal dialysis solutions.
AB  - Pre-clinical biocompatibility testing of peritoneal dialysis (PD) solutions has
      become an integral part of new solution development. The construction of a pre
      clinical screening program for solution biocompatibility should take a
      hierarchical approach, starting with in vitro cell viability and function assays.
      The selection of cell types and assay systems for the in vitro studies should be
      broad enough to permit a balanced interpretation. Whenever possible, animal
      models are recommended for the next hierarchical level of testing, followed by
      human ex vivo study designs. Designs of the latter sort provide evidence that a
      new solution formulation is exerting an altered biological response in vivo; the
      response is not purely an in vitro artifact or restricted to a given animal
      species. This article discusses the various approaches available for
      biocompatibility testing during the pre-clinical phase of solution development,
      with an emphasis on the advantages and drawbacks of each method.

PMID- 11229612
TI  - Biocompatibility of new peritoneal dialysis solutions: clinical experience.
AB  - The successful development of peritoneal dialysis (PD) during the last two
      decades has been made possible by using well-established glucose-based solutions
      with lactate as buffer. On the other hand, awareness has been increasing about
      the potentially negative effects of the high concentrations of glucose and
      lactate, and the low pH of conventional PD solutions. This awareness has prompted
      an intensive effort to search for and test alternative solutions. As a result,
      three new, more biocompatible solutions-containing either less glucose or less
      lactate--are available. Amino acid-based solution uses amino acids instead of
      glucose as the osmotic agent; it is indicated for treatment of malnutrition. The
      higher pH and absence of glucose in this solution may prevent alterations of the
      peritoneal membrane caused by acidity and high glucose concentrations.
      Bicarbonate/lactate-buffered solution contains a physiologic concentration of
      bicarbonate and a reduced concentration of lactate; it also has a physiologic pH
      and markedly reduced levels of glucose degradation products (GDPs). Icodextrin
      based solution contains icodextrin as the osmotic agent; it is indicated for long
      dwells, delivering sustained ultrafiltration for more than 16 hours. This iso
      osmolar glucose-free solution may reduce peritoneal membrane alterations caused
      by glucose or the hyperosmolality (or both) of conventional solutions. Clinical
      experience of the new solutions is now extensive, and their efficacy and safety
      are well documented. It therefore seems appropriate to state that we have entered
      a new era of PD therapy. Each of the new solutions may be less damaging to the
      peritoneal membrane than conventional solution. In addition, they permit better
      management of malnutrition and fluid status, and may thus help to improve PD
      patient survival. Although the effects of each of these new solutions have been
      well described, clinical documentation of the combined use of these new
      biocompatible PD solutions is still insufficient. However, the results of studies
      are expected, during the coming years, to support the combined use of the new
      solutions as the preferred standard practice for PD.

PMID- 11229614
TI  - Biocompatibility of new peritoneal dialysis solutions: what can we hope to
      achieve?
AB  - Despite the bioincompatibility of the "old", standard, high glucose, lactate
      buffered peritoneal dialysis (PD) solutions, PD is itself a highly successful
      dialysis modality with patient survival equivalent to that of hemodialysis (HD)
      during the initial 3 - 5 years of dialysis therapy. Nevertheless, PD technique
      survival is often limited by infectious complications and alterations in the
      structure and function of the peritoneal membrane. These local changes also have
      a negative impact on patient survival owing to systemic effects such as those
      often seen in patients with high peritoneal transport rate and loss of
      ultrafiltration (UF) capacity. Patient mortality remains unacceptably high in
      both HD and PD patients, with most premature deaths being associated with signs
      of malnutrition, inflammation, and atherosclerotic cardiovascular disease (MIA
      syndrome). These systemic signs are likely to be influenced by PD solutions both
      directly and indirectly (via changes in the peritoneal membrane). New,
      biocompatible PD solutions may have favorable local effects (viability and
      function of the peritoneal membrane) and systemic effects (for example, on MIA
      syndrome). Amino acid-based solution [Nutrineal (N): Baxter Healthcare
      Corporation, Deerfield, IL, U.S.A.] may improve nutritional status as well as
      peritoneal membrane viability. Bicarbonate/lactate-buffered solution [Physioneal
      (P): Baxter Healthcare Corporation] may ameliorate local and systemic effects of
      low pH, high lactate, and high glucose degradation products. Icodextrin-based
      solution [Extraneal (E): Baxter Healthcare SA, Castlebar, Ireland] may improve
      hypertension and cardiovascular problems associated with fluid overload and may
      extend time on therapy in patients with loss of UF capacity. The positive effects
      of each of these new, biocompatible solutions have been demonstrated in several
      studies. It is likely that the combined use of N, P, and E solutions will produce
      favorable synergies in regard to both local effects (peritoneal viability) and
      systemic effects (less malnutrition, inflammation, and fluid overload). Solution
      combination is an exciting area for clinical study in the coming years.
      Furthermore, dialysis fluid additives such as hyaluronan, which protects and
      improves the function of the peritoneal membrane, may further improve PD
      solutions. The new, biocompatible PD solutions represent an entirely new era in
      the evolution of the PD therapy; they are likely to have markedly positive
      effects on both PD technique and PD patient survival in coming years.

PMID- 11229615
TI  - Cost-benefit analysis of newer versus older antidepressants--pharmacoeconomic
      studies comparing SSRIs/SNRIs with tricyclic antidepressants.
AB  - Changes in the social and health services over the last years have forced doctors
      to concern themselves with cost benefit calculations and budget forecasting. Cost
      considerations are a (co-) determinant in the choice of antidepressants as well
      as neuroleptics and/or antipsychotics. In recent years, pharmacoeconomic studies
      have been performed to answer the question as to what extent treatment with new
      antidepressants, in particular SSRIs, is actually less expensive than treatment
      with (generic) tricyclic antidepressants due to better safety profiles and higher
      compliance in spite of the considerably higher retail price. Following
      descriptions of the methodological principles, the currently available studies
      are presented and discussed critically in this report. It can be stated that the
      economic value of different antidepressants can not be decided definitively at
      the present time. The available data do not allow the conclusion that SSRIs
      should be preferred over tricyclic antidepressants with the argument that the
      treatment as a whole is more cost effective in spite of the higher costs.

PMID- 11229616
TI  - Towards a more rational use of psychoactive substances in clinical practice.
AB  - Complex knowledge and data intensive nature of the psychoactive drug selection
      and prescription process often makes for irrational and inconsistent use of
      psychoactive drugs in clinical practice. After describing the state of the art
      with respect to psychoactive drug prescription practices and selection processes,
      our aim is to analyze the advantages of computer support systems in assisting the
      clinician in his clinical decisions. Finally, we will review the neuropsychiatric
      expert systems developed for the neuropsychiatric domain. Suboptimal psychoactive
      drug therapy is common practice, which leads to hospital admissions, extended
      length of hospital stay, ineffective therapy and increased costs. Furthermore,
      the psychoactive drug selection process is a complex decision process, using up
      to-date integrative knowledge of drugs from basic sciences to the clinical level.
      Due to the information load, the lack of appropriate up-to-date information at
      the point of clinical care and the problem of integrating and weighing all
      information relatively equally, it is questionable whether any clinician can
      manage such a complex situation with optimal effectiveness. As has been shown in
      a number of experiments, clinicians can benefit from computer-based systems that
      provide access to accurate, up-to-date information. We maintain that more
      rational use of psychoactive drugs in clinical practice is needed, and conclude
      that rational psychoactive drug prescription is a knowledge and data-intensive
      task requiring true expertise derived from clinical, pathophysiological and
      pharmacotherapeutic knowledge. We will be developing a Multidisciplinary
      Psychoactive Drug Selection advisor system, M-PADS, to support the integration of
      various types of biomedical information and deliver that integrated information
      supportive to evidence-based rational drug prescription in the practice of
      medicine for the drug treatment of individual patients.

PMID- 11229617
TI  - Influence of treatment of Tourette syndrome with delta9-tetrahydrocannabinol
      (delta9-THC) on neuropsychological performance.
AB  - Previous studies have suggested that marijuana (cannabis sativa) and delta-9
      tetrahydrocannabinol (delta9-THC), the major psychoactive ingredient of
      marijuana, are effective in the therapy of tics and associated behavioral
      disorders in Tourette Syndrome (TS). Because there is also evidence that cannabis
      sativa may cause cognitive impairment in healthy users, we performed a randomized
      double-blind placebo-controlled crossover trial for delta9-THC in 12 adult TS
      patients to investigate whether treatment of TS with a single dose of delta9-THC
      at 5.0 to 10.0 mg causes significant side effects on neuropsychological
      performance. Using a variety of neuropsychological tests, we found no significant
      differences after treatment with delta9-THC compared to placebo treatment in
      verbal and visual memory, reaction time, intelligence, sustained attention,
      divided attention, vigilance, or mood. Only when using the Symptom Checklist 90-R
      (SCL-90-R) did our data provide evidence for a deterioration of obsessive
      compulsive behavior (OCB) and a trend towards an increase in phobic anxiety.
      However, these results should be interpreted with caution as SCL-90-R has known
      limitations on measuring OCB. We suggest that the increase in phobic anxiety is
      mainly due to the fact that a single-dose treatment rules out the possibility of
      administering the dosage slowly. In contrast to results obtained from healthy
      marijuana users, a single-dose treatment with delta9-THC in patients suffering
      from TS does not cause cognitive impairment. We therefore suggest that further
      investigations should concentrate on the effects of a longer-term therapy of TS
      with delta9-THC.

PMID- 11229618
TI  - Acute and long-term treatment of catatonia with risperidone.
AB  - Catatonia is a rare but difficult-to-treat disorder. Here, we report on the case
      of a schizophrenic patient who developed several episodes of severe catatonia
      after suffering from adequately treated Lyme disease with encephalitis. The
      catatonic stupor was not responsive to typical neuroleptics and benzodiazepines.
      After the medication was changed to risperidone, there was a dramatic and
      persistent improvement of the patient's condition. Two relapses during the follow
      up period over five years were caused by dose reductions. Risperidone might be a
      promising drug in the treatment of acute catatonia and in preventing further
      episodes.

PMID- 11229619
TI  - Serum levels of sulpiride enantiomers after oral treatment with racemic sulpiride
      in psychiatric patients: a pilot study.
AB  - Sulpiride (SULP), a substituted benzamide with high selectivity for D2-like
      dopamine receptors, has a chiral structure and is used in most countries as the
      racemate. In an open pilot study, we investigated 26 inpatients (13 female, 13
      male) with schizophrenic or depressive disorder treated with SULP (mean daily
      dosage 64-1062 mg) administered orally, either as a monotherapy or as an add-on
      treatment to a stable and unchanged medication for 3-60 days. Serum levels of
      total SULP and of its enantiomers were measured by high-performance liquid
      chromatography (HPLC) procedures. Clinically relevant indicators of hepatic and
      renal function as well as retrospectively assessed clinical outcome parameters
      were correlated with serum levels of racemic SULP, L-SULP, D-SULP, and the L:D
      SULP ratio. A significant correlation between mean daily dosage and serum levels
      of SULP, L-SULP, and D-SULP emerged (p < 0.05) which was not influenced by age,
      gender, diagnosis, hepatic, or renal function. The ratio of L:D-SULP serum levels
      was <1 (range 0.66-0.97) in all patients. A slight negative correlation between
      CGI improvement and the ratio of L:D-SULP (p < 0.10) and a positive correlation
      between racemic SULP concentrations and side-effects at endpoint was found (p <
      0.05).

PMID- 11229620
TI  - Serum levels of amitriptyline and therapeutic effect in non-delusional moderately
      to severely depressed in-patients: a therapeutic window relationship.
AB  - In a prospective, open clinical study, the relationship between serum levels of
      amitriptyline (At) and nortriptyline (Nt) and the therapeutic effect after 6
      weeks of treatment was investigated. Serum levels were measured by gas-liquid
      chromatography and the therapeutic effect was assessed by the Hamilton Depression
      Rating Scale (HAMD) and the Clinical Global Impression Scale (CGI). A number of
      25 non-delusional, moderate to severely depressed inpatients were included. A
      therapeutic window relationship was detected by means of regression analysis
      (quadratic model). Low and high serum levels were associated with low therapeutic
      effect. In an intermediate range, the probability of good therapeutic effect was
      increased. This relationship reached significance for the serum levels of At (p <
      0.05) and a trend for the sum of serum levels of At and Nt (p < 0.1). As
      expressed by the regression coefficient r2, about 25% to 35% of the variability
      of therapeutic effect was explained by serum levels. Dichotomized data sets
      according to limits of final values of HAMD and CGI as well as limits of a
      therapeutic window of 70 ng/ml and 200 ng/ml (sum of At and Nt) revealed
      significant differences by means of Fisher's exact test (p < 0.05). Furthermore,
      increased ratios of serum level of Nt per serum level of At were found to be
      associated with decreased therapeutic effect. Thus, the present data support the
      existence of a therapeutic window of serum levels of At in depression. Also
      taking into account other reports, this therapeutic window can be defined as
      being between about 70 and 220 ng/ml. The assay of serum levels of At can be used
      to lower the risk of unsatisfactory therapeutic outcome.

PMID- 11229621
TI  - Benzodiazepine withdrawal-induced catatonia.

PMID- 11229622
TI  - Antipsychotic treatment of schizophrenics at risk for violence.

PMID- 11229623
TI  - The utilization of antidepressants in community-dwelling and institutionalized
      elderly--results form a representative survey in Germany.
AB  - Given its widespread occurrence and consequences, old-age depression has to be
      regarded as a major public health problem. Drug treatment has been proven
      effective in the majority of elderly individuals suffering from depression. This
      study presents pharmacoepidemiological data regarding the use of prescribed
      antidepressants and those purchased over the counter in the elderly. Furthermore,
      it links the data to simultaneously assessed depressive symptomatology. A
      representative survey on the utilization of prescription and over-the-counter
      antidepressant drugs and depressive symptomatology in community-dwelling (n =
      1193) and institutionalized elderly individuals (n = 470) aged 75 and over was
      conducted in an urban region of Germany. Antidepressant use was found to be
      remarkably low (synthetic antidepressants: 2.2% of community dwelling
      individuals, 3.6% of institutionalized individuals; phytopharmaca containing
      hypericum perforatum: 4.2% of community dwelling individuals, 2.8% of
      institutionalized individuals). Two-thirds of the individuals treated with
      synthetic antidepressants received tri- and tetracyclic drugs, which were given
      at lower dosages than recommended for depression treatment. Selective serotonin
      reuptake inhibitors (SSRIs) were introduced in community-dwelling individuals
      only; none of the individuals cared for in residential and nursing homes received
      SSRIs. Only a minority of individuals with depressive symptoms were treated with
      antidepressants. The data suggests underutilization of antidepressants in the
      elderly, in which institutionalized elderly seem especially disadvantaged. The
      results call for increased efforts to discuss mental health issues in the public
      and to share scientific knowledge about symptoms, course and treatment options
      for depression. Furthermore, geronto-psychiatric competence of medical
      professionals, especially GPs, has to be systematically developed.

PMID- 11229624
TI  - Emergency dental service is still needed--also for regular attenders within a
      comprehensive insurance system.
AB  - The aim of this study was to describe types of, and reasons for, emergency visits
      for regular dental attenders in the Public Dental Health Services (PDHS). The
      study was based on data from 895 consecutive emergency episodes collected from
      four PDHS clinics in the county of Ostergotland, Sweden, during a six-month
      period in 1994/95. Forty per cent of the dental emergency visits included
      children and adolescents. The most common reasons for attending were material
      fractures (29%), tooth fractures (19%), pain (19%) and dental traumas (12%).
      Seventy-three per cent of all patients and 60% of children and adolescents knew
      the next scheduled revision appointment. In 85% of the cases care-givers and
      patients were in agreement regarding the urgency of the visit. The care-givers
      considered 14% of the visits non-urgent, only in 1% they felt that the patient
      should have come earlier. The results show that emergency visits are common among
      regular dental care patients, but are dominated nowadays more by answering
      patients' questions and less by pain relief. Via systematic follow-ups and better
      learning from the experiences of those who seek emergency dental care, routines
      could be further developed and considerable benefits achieved concerning both
      perceived service quality and cost-effectiveness.

PMID- 11229626
TI  - Treatment of hypertension with valsartan combined with spironolactone.
AB  - Preliminary observations were made to assess the antihypertensive efficacy and
      safety of treatment with valsartan plus spironolactone. Thirteen hypertensive
      patients were studied, 7 were males (54%), and 6 females (46%) with an age range
      from 61 years to 83 years (mean: 74+/-7.1 years). Patients had a mean daytime
      SBP/DBP of 164+/-9.2/99+/-9.5 mmHg. Echocardiography showed cardiac hypertrophy
      and mild cavity enlargement in all patients. After baseline measurements of HR,
      serum creatinine and electrolytes (potassium and sodium), patients received
      valsartan 80 mg/day plus spironolactone 100 mg/day for concomitant chronic heart
      failure due to hypertension. Study parameters were measured at the 30, 60, and 90
      day of therapy. Mean ambulatory SBP/DBP monitoring, mean Holter heart rate, mean
      serum creatinine, and mean serum electrolytes (sodium and potassium) were
      recorded. These parameters did not show statistically significant changes after
      90 days of follow up, except in one patient who had an increase in serum
      potassium concentration from 4.3 mmol/l to 5.8 mmol/l after 30 days of therapy.
      Mean BP was reduced up a maximum of 7%. No side effect was seen in the study
      patients. Combination therapy valsartan and spironolactone seemed to be an
      effective and safe approach for older hypertensive patients with mild concomitant
      chronic heart failure.

PMID- 11229625
TI  - Fluoride use by gender, age and dental fear among patients in a private practice.
AB  - The present study involved 145 consecutive self-referred patients (89 women, 56
      men) at a private general practice, aimed at identifying whether differences in
      anxiety levels between women and men were related to self-administered fluoride
      prevention. Use of fluoride was assessed using a questionnaire to the use of
      tablets, rinse or other methods in addition to fluoride toothpaste. In logistic
      regression models, with fluoride use as the dependent variable, neither dental
      anxiety, measured by the Dental Anxiety Scale or by the Dental Fear Survey, nor
      age, were related to the use of fluorides. However, there was an association with
      gender. Thus, women used prophylactics 3.5-3.9 times as often as men. Women also
      expressed higher overall levels of dental fear. The probability in logit
      calculations for use of fluoride was highest (18%) for 30 year old women with a
      high DAS score. Additional surveys and research are needed in relation to the
      patient's cognition, attitude and behaviour towards oral disease, in order to
      enhance the success of preventive methods of oral disease and management of
      dental fear.

PMID- 11229627
TI  - Beneficial effect of verapamil added to chronic ACE inhibitor treatment on renal
      function in hypertensive elderly patients.
AB  - This study analysed the effect of low doses of verapamil added to chronic
      treatment with angiotensin-converting enzyme (ACE) inhibitors on blood pressure
      and serum creatinine levels in eight elderly hypertensive patients who had a
      steady increase of serum creatinine while on ACE inhibitors. The study was
      performed in eight elderly hypertensive subjects, five men and three women (mean
      age 70+/-2 years; systolic blood pressure 173+/-4 mm Hg; diastolic blood pressure
      99+/-1 mm Hg) and serum creatinine of 1.60+/-0.27 mg/dl before treatment. During
      an average of 25 weeks, ACE inhibitors significantly reduced both systolic and
      diastolic blood pressures, but serum creatinine levels were increased over basal
      levels (0,68+/-0,20 mg/dl, p < 0.05). During an average of 10 weeks, the addition
      of verapamil did not decrease blood pressure further, but serum creatinine levels
      were reduced to baseline. Our study suggests that the addition of verapamil to
      ACE inhibitors can reverse ACE-induced increase in creatinine levels in elderly
      hypertensive patients in whom this side effect is observed.

PMID- 11229628
TI  - Renal transplantation in patients above 60 years of age in the modern era: a
      single center experience with a review of the literature.
AB  - A retrospective study was conducted of 797 patients receiving renal transplants
      from January 1985 to March 1997. Patient and graft survival was compared for
      patients above and below the age of 60. Sixty-nine patients < or =60 years old
      received 73 kidneys. Race: 73% Caucasian, 26% Black, 1% Other. Sex: 68% M.
      Hypertension (19) and PCKD (15) were the most common diagnoses. Mean peak panel
      reactive antibody (PRA) was 37.7%. Donor age was 2 to 66 years. Mean Cold
      ischemic time was 28.1 hours. Follow-up was until death or until 8/30/97.
      Patients <60 years included: 62% Caucasian, 34% Black, 4% Other; 60% male, Mean
      PRA 39.3. Of the 69 study patients, 27 died: 19 with a functioning graft, 8
      within one year of transplantation. Cardiovascular causes (19 patients, 72%) and
      infection (7 patients, 24%) were most common. Common causes of graft loss were
      death with a functioning graft (19) and chronic rejection (15); other causes were
      acute rejection and primary non-function. Univariate analysis of 18 risk factors
      showed CHF and past history of vascular surgery significantly (p < 0.05) affected
      time of return to dialysis. Multi variate analysis did not show these independent
      variables to be significant. Abnormal ejection fraction and presence of q waves
      on EKG significantly affected time to death (p < 0.05) on uni- and multi-variate
      analysis. After censoring patients that died with functioning grafts, difference
      in graft survival between > or =60 and <59 years was not significant (p > 0.2).
      In this study, 68% of older patients had allografts functioning at 1 year. The
      fact that older patients succumb over time from natural causes should not keep
      patients from transplantation. Immunosuppressive agents need to be limited to
      reduce the incidence of infection. Criteria need to be refined to define those
      who are at prohibitive risk, who may not be candidates for transplantation.

PMID- 11229629
TI  - Hyperkalemia in hospitalized patients.
AB  - OBJECTIVE: Evaluate the prevalence of hyperkalemia (potassium > 5.5 mmol/l) in
      hospitalized patients not on dialysis, as well as the association of medications,
      impaired renal function and comorbid conditions with hyperkalemia. DESIGN: A
      retrospective case-control method. SETTING: A tertiary care teaching hospital.
      PATIENTS: Hyperkalemic adults not on dialysis with age and sex matched controls.
      INTERVENTIONS: None. MAIN OUTCOME MEASURES: The use of medications associated
      with hyperkalemia and renal function using a calculated creatinine clearance were
      compared in the hyperkalemic and control groups. RESULTS: 35 adult patients with
      hyperkalemia who were not receiving dialysis were identified, with a prevalence
      in the hospitalized population of 3.3%. The hyperkalemic patients were older than
      the general hospital population (p < 0.05). Compared with controls, hyperkalemic
      patients: had a lower creatinine clearance (p < 0.05), were more likely to be
      taking angiotensin-converting enzyme inhibitors (p < 0.05), and had an increased
      frequency of diabetes mellitus (p < 0.001). All of the control patients survived
      their hospitalization, but the mortality rate in the hyperkalemic group was 17%
      (p < 0.0001). None of the deaths were directly attributable to hyperkalemia.
      CONCLUSIONS: Hyperkalemia is more frequent in older patients and is usually mild.
      Hyperkalemia is associated with diabetes mellitus, diminished renal function and
      the use of angiotensin-converting enzyme inhibitors. An elevated serum potassium
      level in a hospitalized patient may be a marker for a significantly increased
      risk of death, which is due to underlying medical problems and is not a
      consequence of the hyperkalemia.

PMID- 11229630
TI  - Extrapulmonary tuberculosis in patients with end stage renal disease--two case
      reports and a brief review.
AB  - Chronic renal failure is a risk factor for tuberculosis. In the past five years
      we have identified two cases of tuberculosis in our dialysis population. The
      first patient, showed chronic failure to thrive on hemodialysis. An enlarged
      cervical lymph node was biopsied and, although no acid fast bacilli (AFB) were
      seen, a culture grew Mycobacterium tuberculosum (TB). Her chest X-ray did not
      show evidence of past tuberculosis. The second patient was a long time smoker who
      presented with an enlarged cervical node, which was biopsied. AFB were not seen
      on her biopsy, but her culture grew TB. Extrapulmonary TB is common in patients
      with ESRD, and lymph node involvement is the most common extrapulmonary
      presentation. Screening with the purified protein derivative (PPD) is not helpful
      in ESRD patients, since defects in cell mediated immunity are common. A high
      index of suspicion for TB is warranted in patients with ESRD.

PMID- 11229631
TI  - Severity of illness scores and the outcome of acute tubular necrosis.
AB  - The outcome of patients with acute renal failure (ARF) due to acute tubular
      necrosis (ATN) was evaluated in this study. Two hundred and twenty-two patients
      with a mean age of 55.1+/-17.7 years (range 19-97 years; male 153, female 69) who
      developed ATN in the period from July 1991 through January 1997 were studied.
      Patients were divided into four groups according to their APACHE II scores at the
      time of the diagnosis of ATN. Group I included patients with an APACHE II score
      of 14 or less (n = 70), Group II with a score of 15-18 (n = 52), Group III with a
      score of 19-23 (n = 58), and group IV with a score of 24 or above (n = 42). The
      mean APACHE II score for each of the four study groups was 11+/-0.4, 16+/-0.2,
      20+/-0.2, and 29+/-0.7, respectively. Patient survival was evaluated by the
      Kaplan-Meier analysis with censorship at 12 months. Survival rates at 180 days
      were 67%, 47%, 39%, and zero%, for group I through IV respectively, chi2 = 27.99,
      p < 0.0001, with a median survival of >365, 120, 31, and 11 days, for groups I
      through IV, respectively. For patients with oliguria (n = 88) survival at 180
      days was 23% vs. 58% for patients without oliguria (n = 134), p < 0.0001, median
      survival 13 vs. 364 d. Six months survival of those who required dialysis (n =
      79) was 25% vs. 58% for those whom dialysis was not needed (n = 143), p = 0.001,
      median survival 15 vs. 364 d, respectively. In patients with sepsis (n = 58), 6
      months survival was 35% vs. 50% for those without sepsis (n = 164), p = 0.013,
      median survival 14 vs. 169 d. In patients who required mechanical ventilation (n
      = 72), 6 months survival was 17% vs. 62% for those who did not need respiratory
      support (n = 150), p = 0.0001, median survival 13 vs. > 365 d, respectively.
      Finally, 6 months survival in patients with one (kidney only), two, three, and
      four organ failure was 76, 30, 11, and zero percent, respectively, p = 0.0001,
      median survival >365, 16, 11, and 12 days, respectively. We conclude that the use
      of the APACHE II score for the stratification of the severity of illness could be
      of clinical utility in predicting mortality in patients with ATN. Other
      predictors of poor prognosis include the need for dialysis, the presence of
      oliguria, the need for mechanical ventilation, the presence of sepsis, and the
      number of failed organs.

PMID- 11229632
TI  - Renal transplantation in the elderly.
AB  - Recent data show that, despite a long period during which few elderly patients in
      end-stage renal failure received grafts, there are neither medical nor ethical
      grounds for avoiding kidney transplantation, at least in those aged under 70 or
      even 75 years of age. Units in which transplantation in older recipients is
      routine show a good survival of recipients, and comparable survival of grafts to
      those placed in younger recipients. This equality of graft survival with age
      arises because, although death with a functioning graft is more common in the
      elderly (principally from cardiovascular disease and infections, with malignant
      diseases becoming more important with time), graft losses from rejection are
      lower, and so overall outcomes are similar. Long-term patient survival is better,
      quality of life is improved and treatment is cheaper than in comparable elderly
      patients maintained on hemodialysis or chronic ambulatory peritoneal dialysis. In
      terms of allocation to older recipients, this success presents major practical
      and ethical difficulties given the shortage of cadaver organs. Data do not
      support the idea of 'age-matching' older or marginal kidneys to older recipients:
      like their younger counterparts, older recipients do better with organs from
      younger donors. Living donors can be used successfully even in those over 70, and
      elderly living donors have a place in the treatment of the elderly. The optimum
      immunosuppressive regimes for elderly recipients have not been determined, given
      their poorer immune responsiveness and lower rejection rates compared with
      younger individuals.

PMID- 11229633
TI  - N-acetyl-glucosaminidase (NAG) excretion in partially obstructed weanling rats.
AB  - The understanding of pathophysiology of obstructed uropathy has been facilitated
      by animal models with partial ureteric obstruction. Some studies on partially
      obstructed adult rats have drawn attention to a biphasic pattern of obstructive
      uropathy: an initial 'destructive' phase and a 'steady' phase in which renal
      deterioration no longer occurs and in which relief of obstruction would be of no
      advantage. We aimed to verify if this pattern applies also to younger (weanling)
      rats with more immature kidneys, resembling those of the human fetus. We measured
      the NAG-values in the urine samples of partially obstructed animals at different
      intervals of obstruction and in those of controls. The biphasic pattern proved to
      be the same as in adult rats as was previously documented, but the turning point
      occurred earlier (between 10 and 15 days of obstruction). Furthermore, there is
      evidence of low level values of N-Acetyl-Glucosaminidase (NAG) in the early phase
      of obstruction (5 days), demonstrating that the increase of tubular enzyme is not
      due to the operation itself. There is evidence that, if the 'destructive' phase
      can be precisely identified by biochemical studies, this could help identifying
      those subjects who could benefit from relief of obstruction.

PMID- 11229634
TI  - Giant angiomyolipoma associated with marked pulmonary lesions suggesting
      lymphangioleiomyomatosis in a patient with tuberous sclerosis.
AB  - The association between Tuberous Sclerosis (TS) and Angiomyolipoma (AML) is well
      known. A patient with TS and giant AML mimicking Renal Cell Carcinoma (RCC),
      measuring 29 x 18 x 11 cm, weighing 4700 gr is presented. Imaging studies
      revealed coexistent pulmonary lymphangioleiomyomatosis and concurrent renal and
      pulmonary involvement is extremely rare in patients in TS. We believe that the
      growth potential of this hamartomatous lesion may reach to a life threatening
      size.

PMID- 11229635
TI  - Double partial nephrectomy in a patient with two adenocarcinomas in a solitary
      kidney.
AB  - We present a 67 year-old female patient with two synchronous adenocarcinomas in a
      solitary kidney. She underwent thorough clinical and radiographic evaluation.
      Selective angiography proved to be the most reliable examination in preoperative
      diagnosis. Double partial nephrectomy was performed and the patient has normal
      renal function and no evidence of recurrence 27 months postoperatively. Partial
      nephrectomy in patients with one tumor in a solitary kidney is well documented,
      though we believe that partial nephrectomy can also be performed in selected
      cases with multifocal tumors.

PMID- 11229636
TI  - Primary cyst hydatid of adrenal: a case report.
AB  - Adrenal cysts are very rare lesions, especially with parasitic origin. Here,
      primary cyst hydatid of adrenal in a 51 years old woman who consulted with a left
      flonk pain, is presented and the literature is reviewed.

PMID- 11229637
TI  - Haemorrhagic complications of percutaneous lithotripsy: original methods of
      treatment.
AB  - 698 patients treated for nephrolithiasis with the application of percutaneous
      lithotripsy were analysed. In 32 cases increased bleeding in the course of the
      procedure occurred. It was controlled without surgery with blood transfusion,
      constant renal saline flow maintenance, electrocoagulation, kidney parenchyma
      pressing with thick drain and approach canal tamponade. In one case the approach
      to the kidney was obtained surgically and the kidney parenchyma was stitched with
      haemostatic suture. One patient required selective embolization due to kidney
      haemorrhage after nephrostomy drain removal.

PMID- 11229638
TI  - Comparision of intracorporeal lithotripsy methods and forceps use for distal
      ureteral stones: seven years experience.
AB  - OBJECTIVES: To evaluate and to compare the safety and efficacy of ureteroscopic
      lithotripsy methods and forceps use for distal ureteral stones. MATERIALS AND
      METHODS: 514 patients were evaluated retrospectively who were treated by dye
      laser, electrohydraulic or ultrasonic lithotripsy or direct forceps extraction
      for distal ureteral stones between May 1992-October 1999. RESULTS: Laser
      lithotripsy was determined to be the most effective method with 86.9% success,
      while ultrasonic lithotripsy was the least effective method with 77.3% success
      rate. For smaller stones forceps extraction had a 88.5% success rate. CONCLUSION:
      Ureteroscopic lithotripsy methods are all alternative choice of treatment methods
      in distal ureteral stones. To our experience, laser lithotripsy is the most
      effective method of all intracorporeal lithotripsy methods as far as the success
      and complication rates are concerned.

PMID- 11229639
TI  - Bladder perforation caused by foreign body migration.
AB  - Lower urinary tract symptoms is a well known presentation of the presence of
      foreign bodies inside the bladder. Most such cases are diagnosed by chance, while
      investigating unrelated conditions. We present the transvesical endoscopic
      extraction of a surgical sponge that migrated to the bladder six years after an
      inguinal hernioplasty.

PMID- 11229640
TI  - Urinary tract infection and antibiotic susceptibility in malnourished children.
AB  - In this study, 31 (30%) cases of urinary tract infection (UTI) of 103 patients
      with malnutrition, who were admitted to our hospital, were investigated
      prospectively. Our purpose was to determine the frequency of UTI, species of
      bacteria caused to infection and their antibiotic susceptibility in infants with
      malnutrition. The mean age of the patients with UTI was 11.5+/-7.6 months
      (ranging 50 days-30 months). The main symptoms were fever, vomiting, diarrhea,
      cough, and seizures. The mean body weight was 5.8+/-1.9 kg (2-10 kg), and height
      was 67.5+/-7.8 cm (53-85 cm). Seven of them had mild, 11 had moderate, and 13 had
      severe malnutrition. The most common isolated microorganism from urine cultures
      was Escherichia coli (54.8%). Most strains of Escherichia coli were resistant to
      co-trimoxazole (82.3%), ceftriaxone (17.6%), cefotaxime (17.6%), and
      ciprofloxacine (17.6%), but none of them were resistant to gentamicin. In
      conclusion, we would like to emphasize that UTI predominantly by gram negative
      microorganisms are frequent in the infants with malnutrition, and these
      microorganisms are mostly resistant to co-trimoxazole which is used commonly in
      practical medicine and prophylaxis.

PMID- 11229642
TI  - The rate of urgency symptoms in women with stress urinary incontinence and
      nomogram based bladder outlet obstruction.
AB  - We reviewed the charts of 132 women 30 of whom were chosen as obstructed, 30
      equivocal and 72 as unobstructed by automatically given nomograms in the
      urodynamic evaluation for stress incontinence. The rates of urgency symptoms in
      nomogram based obstructed, equivocal and unobstructed cases of stress
      incontinence were found in 30%, 23.3% and 12.5% respectively. More urgency
      symptoms were observed in women with stress incontinence and nomogram based
      bladder outlet obstruction than in equivocal and unobstructed cases.

PMID- 11229641
TI  - Concomitment spread of a renal cell carcinoma beyond the kidney and a
      transitional cell carcinoma beyond the bladder.
AB  - We report the case of a 61-year-old man, with a rare combination of two advanced
      urological tumors: a concomitant spread of an adenocarcinoma beyond the kidney
      and a urothelial carcinoma beyond the bladder. We simultaneously performed a
      primary curative prostatovesiculectomy and a nephroureterectomy on the right with
      ileal neobladder. To our knowledge, a case report of concomitant spread of an
      adenocarcinoma beyond the kidney (pT3 pN0 M0 G3) and a urothelial carcinoma
      beyond the bladder (pT3a pN0 M0 G3) with subsequent curative therapy has thus far
      not been published. A combination of the two diseases described here is obviously
      a remarkable rarity.

PMID- 11229643
TI  - The inguinal bladder diverticulum: a rare differential diagnosis of hernias.
AB  - We report a rare case of an inguinal herniation of a large bladder diverticulum
      due to obstructive uropathy. Diagnostic means, therapeutic strategies and
      complications are discussed.

PMID- 11229644
TI  - The nested variant of the transitional cell bladder carcinoma: a case report and
      review of the literature.
AB  - The nested variant of transitional cell carcinoma is extremely rare in the
      bladder. Here we reported a new case and review the literature.

PMID- 11229645
TI  - The distribution of S-100 protein in hyperplastic and neoplastic prostatic
      epithelium.
AB  - Specimens from 30 cases of benign prostatic hyperplasia and 75 cases of prostatic
      carcinoma obtained during suprapubic prostatectomy, transurethal resection of the
      prostate and radical prostatectomy, were stained immunohistochemically for S-100
      protein, prostatic acid phosphatase (PAP), prostatic specific antigen (PSA),
      neuron specific enolase (NSE) and polyclonal keratin. S-100 protein was positive
      in 9.3% of prostatic carcinomas and negative in all cases of prostatic
      hyperplasia. PAP and PSA were positive in all cases, while NSE was positive in
      16% of the carcinoma cases. Polyclonal keratin was positive in both cell layers
      of the double layered hyperplastic prostatic epithelium with a more intense
      staining pattern in the outer cell layer. The authors believe that the S-100
      protein immunoreactivity observed in some prostatic carcinomas, reflecting the
      change in the functional status of the neoplastic cells, might be of prognostic
      significance. They also emphasize the non-myoepithelial nature of the outer cell
      layer of the double layered prostatic epithelium.

PMID- 11229646
TI  - Immunohistochemical detection of retinoic acid receptor-alpha in prostate
      carcinoma: correlation with proliferative activity and tumor grade.
AB  - BACKGROUND: The use of retinoids as differentiation therapy is a novel approach
      to prostate cancer. Retinoids act via their own nuclear receptors, RARs and RXRs,
      modulating gene activity, cell growth and differentiation. This study provides
      new data on the content and cellular distribution of RARalpha protein in prostate
      cancer specimens, in correlation to tumor grade and proliferative activity.
      MATERIAL AND METHODS: A total of 84 cases of primary prostate carcinoma, divided
      into 3 subgroups according to tumor grade, were immunohistochemically evaluated
      for retinoic acid receptor-alpha (RARalpha) and Ki67 using the
      streptavidin/peroxidase method on formalin fixed, paraffin embedded tissues.
      RESULTS: RARalpha positivity was detected in all cases of prostatic carcinoma,
      with a more profound expression in well differentiated cancers. A statistically
      significant correlation between RARalpha staining and tumor grade was found
      (ANOVA, p < 0.031). Ki67 immunoreactivity was present in 35.7% of cases, but no
      correlation with tumor grade was found. When RARalpha staining was correlated
      with Ki67 positivity, a statistically significant correlation was present
      (unpaired t-test, p < 0.003). CONCLUSIONS: These findings indicate that RARalpha
      expression is correlated to some extent with tumor grade and its presence is more
      profound in highly proliferative tumors. Further studies are needed to establish
      the possible clinical value of the immunohistochemical evaluation of RARalpha
      content in tumor specimens.

PMID- 11229647
TI  - Changes of serum prostate-specific antigen following high energy thick loop
      prostatectomy.
AB  - We evaluated the effect of the high electrocuting energy used with the thick
      loop, in transurethral vaporization resection of the prostate (TUVRP), on serum
      prostate-specific antigen (PSA). Forty-eight patients with benign protatic
      hyperplasia (BPH) were included in this prospective single arm sequential study.
      All patients had TUVRP using the 'Wing' thick resection electrode (Richard Wolf,
      Germany). Serum PSA was measured before, 1 day and 6 weeks in the morning post
      TUVRP. PSA values were correlated to preoperative prostate size and to prostatic
      resection weight. Serum PSA values (mean +/- SD) were 6.29+/-4.4 ng/ml, 14.9+/
      11.1 and 2.3+/-1.9 before, 1 day and 6 weeks post TUVRP respectively. The mean
      increase in the PSA at 1 day over baseline value was 2.72, this was statistically
      significant (p < or = 0.0001). The PSA level returned to less than pre TUVRP
      value in all but 3 patients by 6 weeks. The PSA value 1 day post TUVRP correlated
      well with the pre PSA level, prostate size and prostatic resection weight (r =
      0.58, r = 0.38 and r = 0.44 respectively) however, the PSA level at 6 weeks
      correlated only to pre TUVRP values (r = 0.53). We conclude that that serum PSA
      is not reliable within 6 weeks of TUVRP. The reversible increase in serum PSA
      value is similar to other forms of prostatectomy which, suggests that the
      increased level of electrosurgical energy that is used in TUVRP does not have an
      added adverse effect on the PSA levels.

PMID- 11229648
TI  - Three dimensional conformal radiotherapy in patients with T2a-b, N0, M0 prostatic
      carcinoma.
AB  - The current study was undertaken to evaluate the Prostate Specific Antigen (PSA)
      relapse free survival and the prognostic factors in a total of 38 patients with
      stages of T2a-b, N0, M0 prostate carcinoma treated with three-dimensional
      conformal radiotherapy (3D-CRT). Mean 69.63 Gy was given with 3D-CRT, the mean
      follow up time was 13.89 months, and the mean prebiopsied PSA level was 25.12
      ng/ml. The 2-year PSA relapse free survival was 47.37% for the entire group. The
      2-year PSA relapse free survival rates were 100% and 44.74% for the patients with
      Gleason score < or = 7 and greater than 7 (p < or = 0.05). Patients with
      prebiopsied PSA level < or = 10 ng/ml and the stages of T2a or T2b did not show
      any significant differences (p > or = 0.05). Although the few case number and
      short term follow up, in this study 3D-CRT was a new effective technique to
      prostate cancer for our institutes and the Gleason score was important predictor
      of PSA relapse free survival.

PMID- 11229649
TI  - Incidental presentation of leiomyoma of bladder with carincoma of the prostate.
AB  - We report a case of bladder leiomyoma found incidentally in a 66-year-old man
      during his work up for an adenocarcinoma of the prostate. Transrectal MRI scan
      appeared to be highly demonstrative of its localization and extent within the
      bladder wall. It was resected transurethrally.

PMID- 11229650
TI  - Tibia metastasis without prostate specific antigen (PSA) increase following
      radical vesiculo-prostatectomy.
AB  - OBJECTIVES: PSA is regarded as the best method in the follow-up of prostate
      carcinoma. After radical vesiculo-prostatectomy the prostate carcinoma seldom
      recurs at zero or nearly zero PSA levels. METHODS: The authors have used PSA
      since 1989 and they have found only one case where metastasis in the tibia came
      without an increase in PSA levels. RESULTS: Tibia metastasis showed lower tissue
      activity of PSA than did the primary tumor in the prostate. The authors think
      this explains the zero PSA level when the metastasis developed. CONCLUSIONS: The
      authors think based on their case that PSA free progression prostate cacncers may
      cases where the metastases do not produce PSA.

PMID- 11229651
TI  - Urethral hemangioma: laser treatment.
AB  - Urethral hemangioma is a rare cause of hematuria for which various modalities of
      treatment have been used. We report a young patient, who presented with hematuria
      and in whom urethrocystoscopy showed multiple hemangiomas in penile urethra.
      These were fulgurated successfully with Nd-YAG laser.

PMID- 11229652
TI  - A case of female epispadias without exstrophy treated with a novel vulvoplasty
      method.
AB  - Epispadias surgery has mainly two components: bladder and genitourethral
      reconstruction. Herein, a novel vulvoplasty method, an alternative for the latter
      component, carried out in a rare case of female epispadias was presented. In a 6
      year-old girl admitted with complaint of total incontinence, epispadias without
      evident extrophy associated with adequate bladder capacity was determined.
      Firstly the vulvoplasty in which a circumferencial skin flap around the urethral
      meatus was rolled backwards, and secondly bladder neck reconstruction was
      performed. The vulvoplasty resulted in sufficient cosmetic outcome and continence
      up to half an hour, and after cervicoplasty total day and night continence at
      rest or on exertion were obtained. It was concluded that this vulvoplasty with
      sufficient cosmetic outcome could be considered as a first stage operation in
      female epispadias, because it could facilitate bladder neck reconstruction by
      increasing urethral resistance, and contribute to continence.

PMID- 11229653
TI  - Spontaneous regression of bilateral surrenal haematoma and subclinical
      hypoaldosteronism in a patient with renal amyloidosis secondary to Familial
      Mediterranean Fever.
AB  - This report describes a patient with Familial Mediterranean Fever (FMF)
      associated with renal amyloidosis, bilaretal surrenal haematomas and
      hypoaldosteronism which was clinically asymptomatic. The deposition of AA
      amyloide was found on the renal and bone marrow biopsies. Bilateral surrenal
      haematoma regressed after six month from the first events. Colchicine therapy
      controlled the attacks of the disease.

PMID- 11229654
TI  - Hydrocortisone, prednisolone and dexamethasone act on Aspergillus fumigatus in
      vitro susceptibility to itraconazole.
AB  - In a previous in vitro investigation from the same laboratory a therapeutic level
      of hydrocortisone enhanced the itraconazole susceptibility of a single strain of
      Aspergillus fumigatus. In the present work, the influence of therapeutic levels
      of hydrocortisone (1 microM), prednisolone (0.125 microM 0.25 microM and 0.5
      microM) and dexamethasone (0.25 microM and 0.5 microM) on the itraconazole
      susceptibility of four A. fumigatus strains, was determined. A. fumigatus conidia
      were germinated either in the absence or in the presence of a glucocorticoid. The
      germinated conidia were then spread onto plates and grown either in the presence
      or in the absence of a glucocorticoid, together with increasing concentrations of
      itraconazole. The mean colony forming units (CFU) were measured. Two factor
      analyses of variance showed that hydrocortisone significantly (p <0.001)
      potentiated the action of itraconazole. The cytotoxic effect of prednisolone on
      the fungal strains added significantly to the effect of itraconazole (p <0.001).
      Dexamethasone was also cytotoxic to the fungus but, when used in conjunction with
      itraconazole, it effectively increased (p <0.01) the number of CFU. This study
      showed a direct effect of glucocorticoids, currently in use for patient therapy,
      on in vitro A. fumigatus susceptibility to itraconazole.

PMID- 11229655
TI  - Transformation of Curvularia lunata IM 2901 with pAN7-1 influences selected
      physiological properties of the fungus.
AB  - Genetic analysis of Curvularia lunata IM 2901 transformants, previously obtained
      by electroporation with plasmid pAN7-1, was carried out. Isolates displayed
      several differences in hygromycin B resistance and their physiology. It was shown
      that plasmid pAN7-1 was integrated in different copy numbers and at different
      positions in the genome of the strains studied. Both the wild type and pAN7-1
      isolates, when growing in liquid media, produced an extracellular emulsifying
      agent. The transformants differed in their growth kinetics, intensity of
      surfactant production and in the efficiency of cortexolone 11beta-hydroxylation,
      in comparison with the wild type. The micro-organisms varied in susceptibility to
      the lytic enzyme complex (Novozyme 234), which indicated the presence of
      differences in their cell wall composition and/or in architecture caused by an
      integrated plasmid pAN7-1.

PMID- 11229656
TI  - Molecular characterization of Salmonella weltevreden isolated from poultry:
      evidence of conjugal transfer of plasmid and antibiotic resistance.
AB  - Ten strains of Salmonella weltevreden isolated from poultry sources were examined
      and found to contain plasmid DNA ranging in size from 1.8 to 68.5 MD. All
      isolates were susceptible to carbenicillin, cephalothin, ceftriazone, gentamicin,
      kanamycin and nalidixic acid, but resistance to bacitracin (100%), penicillin G
      (100%), rifampicin (100%), sulphamethoxazole (100%), cefuroxime (80%) and
      tetracycline (60%) was recorded. The 55 MD plasmid of strain SW5 determined
      resistance to penicillin G and tetracycline, which was transmissible to the E.
      coli K12 recipient at a frequency of 3.52 x 10(-5) transconjugants per input
      donor cell. The results of arbitrarily primed polymerase chain reaction (AP-PCR),
      using two 10-mer oligonucleotides and PCR-ribotyping to differentiate between the
      ten strains of S. weltevreden were compared. The strains were separated into ten
      different genome types by AP-PCR but were indistinguishable by PCR-ribotyping.
      These results suggest that poultry may constitute a reservoir for disseminating
      antibiotic resistance and that AP-PCR may be a valuable tool for epidemiological
      studies.

PMID- 11229657
TI  - Ultrastructural localization of succinate dehydrogenase in some bacteria, after
      treatment with Lubrol W1.
AB  - The localization of succinate dehydrogenase in some gram-negative and gram
      positive bacteria (Salmonella typhimurium, Pseudomonas pseudomallei, Pseudomonas
      aeruginosa and Listeria monocytogenes) treated with the surface membrane active
      agent, Lubrol W1, was studied by a cytochemical method combined with electron
      microscopy.

PMID- 11229658
TI  - PCR cloning of the resuscitation-promoting factor (Rpf) gene from Micrococcus
      luteus, sequencing and expression in Escherichia coli.
AB  - A polymerase chain reaction (PCR) cloning procedure was developed for the
      resuscitation-promoting factor (Rpf) gene of Micrococcus luteus using strains
      NCIMB 13267, JCM 1464T, JCM 3347, and JCM 3348. A PCR product of the Rpf gene
      fragment was ligated into a cloning vector pBluescript II KS (+) with the
      restriction endonucleases Eco RI and Bam HI. The ligation mixture was used to
      transform Escherichia coli DH5alpha. The DNA sequence of the Rpf gene cloned from
      strain JCM 1464T was 84% homologous with that of NCIMB 13267, and from strains
      JCM 3347 and JCM 3348 it was 100% and 86% homologous, respectively. Recombinant
      Rpf proteins of M. luteus NCIMB 13267 and JCM 1464T after expression in E. coli
      BL21 harbouring the pET-19b-Rpf plasmid, and after purification, were
      approximately 16 kD for both strains.

PMID- 11229659
TI  - Interrelation between synthesis and uptake of ectoine for the growth of the
      halotolerant Brevibacterium species JCM 6894 at high osmolarity.
AB  - The growth of a halotolerant Brevibacterium sp. JCM 6894 was examined in the
      presence of compatible solutes such as glycine betaine, ectoine (2-methyl-4
      carboxy-3,4,5,6-tetrahydropyrimidine) and ectoine derivatives. The effect of
      competition between their uptake and synthesis in the cells was subjected to
      osmotic shift towards the higher salinity. Among each solute examined the
      supplement of ectoine or hydroxyectoine exhibited a remarkable stimulation on the
      growth of strain JCM 6894, regardless of the range of osmotic shifts, where the
      largest was 0-->2 M NaCl, the intermediate was 1-->2 M NaCl, and no shift was 2-
      >2 M NaCl. The growth rates of this strain were dependent on the amount of
      ectoine taken up, which was conspicuous for the largest osmotic shift and during
      the first few hours of incubation after transfer. The cells subjected to 1-->2 M
      NaCl and 2-->2 M NaCl transfers took up less ectoine and this resulted in lower
      growth rates than those of cells with the largest osmotic shift (0-->2 M NaCl).
      The role of other compatible solutes which accumulated is discussed in relation
      to growth stimulation of strain JCM 6894.

PMID- 11229660
TI  - The human genome, in proportion.

PMID- 11229661
TI  - How sugar-containing drinks might increase adiposity in children.

PMID- 11229662
TI  - Molecular cytogenetics in cancer.

PMID- 11229663
TI  - Does essential tremor originate in the cerebral cortex?

PMID- 11229664
TI  - Lessons from hand transplantations.

PMID- 11229665
TI  - Will MRI provide maps of lines of excision for rectal cancer?

PMID- 11229666
TI  - Light brought to a standstill.

PMID- 11229667
TI  - Accuracy of magnetic resonance imaging in prediction of tumour-free resection
      margin in rectal cancer surgery.
AB  - BACKGROUND: Incomplete surgical removal of the circumferential tumour spread is
      believed to be the main cause of local recurrence after resection of rectal
      cancer. This study assessed the accuracy of magnetic resonance imaging (MRI) with
      a phased-array coil for preoperative staging and prediction of the distance of
      the tumour from the circumferential resection margin in a total mesorectal
      excision. METHODS: 76 patients with primary rectal cancer were preoperatively
      assessed by MRI at 1.5 T, with a phased-array coil. Two observers independently
      scored, on two occasions, the tumour stage and measured the distance to the
      mesorectal fascia. Their findings were compared with the final histological
      findings. FINDINGS: The MRI tumour stage agreed with the histological stage in 63
      (83%) of 76 patients (weighted kappa=0.77 [95% CI 0.66-0.89]) for observer 1, and
      in 51 (67%) patients (weighted kappa=0.52 [0.37-0.67]) for observer 2. The
      intraobserver agreement on the tumour stage was good (kappa=0.80 [0.69-0.91]) for
      observer 1 but moderate (kappa=0.49 [0.34-0.65]) for observer 2. The
      interobserver agreement was moderate (kappa=0.53 [0.38-0.69]). In 12 patients
      with an obvious T4 tumour, a margin of 0 mm was correctly predicted. Of 29
      patients for whom the pathologist reported a distance of at least 10 mm without
      specifying the actual distance, a distance of at least 10 mm was predicted in 28
      by observer 1 and 27 by observer 2. For the remaining 35 patients, a regression
      curve was constructed; from this, a histological distance of at least 1.0 mm can
      be predicted with high confidence when the measured distance on MRI is at least
      5.0 mm. INTERPRETATION: MRI with a phased-array coil showed moderate accuracy and
      reproducibility for predicting the tumour stage of rectal cancers. The clinically
      more important circumferential resection margin can, however, be predicted with
      high accuracy and consistency, allowing preoperative identification of patients
      at risk of recurrence who will benefit from preoperative radiotherapy, more
      extensive surgery, or both.

PMID- 11229668
TI  - Relation between consumption of sugar-sweetened drinks and childhood obesity: a
      prospective, observational analysis.
AB  - BACKGROUND: The rising prevalence of obesity in children has been linked in part
      to the consumption of sugar-sweetened drinks. Our aim was to examine this
      relation. METHODS: We enrolled 548 ethnically diverse schoolchildren (age 11.7
      years, SD 0.8) from public schools in four Massachusetts communities, and studied
      them prospectively for 19 months from October, 1995, to May, 1997. We examined
      the association between baseline and change in consumption of sugar-sweetened
      drinks (the independent variables), and difference in measures of obesity, with
      linear and logistic regression analyses adjusted for potentially confounding
      variables and clustering of results within schools. FINDINGS: For each additional
      serving of sugar-sweetened drink consumed, both body mass index (BMI) (mean 0.24
      kg/m2; 95% CI 0.10-0.39; p=0.03) and frequency of obesity (odds ratio 1.60; 95%
      CI 1.14-2.24; p=0.02) increased after adjustment for anthropometric, demographic,
      dietary, and lifestyle variables. Baseline consumption of sugar-sweetened drinks
      was also independently associated with change in BMI (mean 0.18 kg/m2 for each
      daily serving; 95% CI 0.09-0.27; p=0.02). INTERPRETATION: Consumption of sugar
      sweetened drinks is associated with obesity in children.

PMID- 11229669
TI  - Effect of pravastatin on frequency of fracture in the LIPID study: secondary
      analysis of a randomised controlled trial. Long-term Intervention with
      Pravastatin in Ischaemic Disease.
AB  - BACKGROUND: Statins inhibit the same biochemical pathway as aminobisphosphonates,
      therefore these cholesterol-lowering agents may have a beneficial effect on
      osteoporosis. This possibility has been supported by the finding that some
      statins also stimulate bone formation, and by observational studies suggesting
      that patients using statins have higher bone densities and lower fracture rates
      than controls. To assess whether statins have clinically significant effects on
      bone, we studied the frequency of fractures in a large randomised controlled
      trial of these agents. METHODS: 9014 patients (17% women, median age 62 years)
      with ischaemic heart disease were randomly assigned pravastatin 40 mg daily or
      placebo and followed up for a mean of 6.0 years. Fractures were ascertained from
      adverse-event reports. FINDINGS: 101 patients in the placebo group were admitted
      to hospital for fracture compared with 107 in the pravastatin group (hazard ratio
      1.05 [95% CI 0.80-1.37]). When patients with fractures not necessitating hospital
      admission were added, the total number of patients having a fracture was 183 in
      the placebo group and 175 in the pravastatin group (0.94 [0.77-1.16]). Separate
      analyses for women alone and for individuals aged 65 years and over gave similar
      results. INTERPRETATION: These findings offer no support for the hypothesis that
      statins have a significant effect on fracture risk. However, this study was not
      of an osteoporotic population, and fracture rate, although clinically important,
      is an insensitive index of effects on bone. Statins should not be used to prevent
      osteoporosis until there is evidence for their efficacy based on randomised
      controlled trials.

PMID- 11229670
TI  - Epidemiology of transmission of cytomegalovirus from mother to preterm infant by
      breastfeeding.
AB  - BACKGROUND: Breastfeeding practices strongly influence the epidemiology of human
      cytomegalovirus infection. By contrast with term neonates, few data are available
      on transmission of infection from mothers to preterm infants during
      breastfeeding. METHODS: 151 mothers and their 176 preterm infants (gestational
      age at birth <32 weeks or birthweight <1500 g) were prospectively screened for
      cytomegalovirus infection by serology, virus culture, and PCR. The roles of cell
      free and cell-associated cytomegalovirus excretion during lactation were analysed
      longitudinally in relation to transmission, by maximum-likelihood estimates.
      FINDINGS: Of the 69 seronegative breastfeeding control mothers, none had
      detectable cytomegalovirus DNA in breastmilk and none of their 80 infants shed
      the virus in urine. The proportion of cytomegalovirus reactivation in
      seropositive breastfeeding mothers was 96% (73 of 76). The early appearance of
      viral DNA in milk whey (median 3.5 days post partum in transmitters; 8 days in
      non-transmitters; p=0.025) and infectious virus in milk whey (10 days and 16
      days, respectively; p=0.005) were risk factors for transmission. The cumulative
      rate of transmission was 37% (27 of 73 mothers; 33 infants). The infection of the
      neonates had a mean incubation time of 42 days (95% CI 28-69). About 50% of the
      infected infants had no symptoms, but four had sepsis-like symptoms.
      INTERPRETATION: The proportion of cytomegalovirus reactivation during lactation
      almost equals maternal seroprevalence. Breastfeeding as a source of postnatal
      cytomegalovirus infection in preterm infants has been underestimated and may be
      associated with a symptomatic infection.

PMID- 11229671
TI  - Tremor-correlated cortical activity in essential tremor.
AB  - BACKGROUND: In patients with parkinsonian resting tremor, tremor-correlated
      activity in the contralateral sensorimotor cortex has been studied by both
      magnetoencephalography (MEG) and electroencephalography (EEG). In essential
      tremor, MEG failed to detect cortical involvement. The objective of this study
      was to investigate whether EEG recording can reveal tremor-correlated cortical
      activity in patients with essential tremor or enhanced physiological tremor.
      METHODS: Seven patients with essential tremor and three patients with enhanced
      physiological tremor participated in the study. Unilateral postural tremor was
      activated by wrist extension on the right or on the left side. Electromyography
      (EMG) signals arising from the wrist extensor and flexor muscles, and a high
      resolution EEG were recorded simultaneously. Coherences between the time series
      of the rectified tremor EMG and the EEG were estimated. FINDINGS: In five of nine
      arms with essential tremor, we found highly significant coherences at the tremor
      frequency between the tremor EMG and the EEG. Isocoherence maps illustrating the
      topography of significant coherences over the scalp showed that the maximum
      coherences were located over the contralateral sensorimotor cortex. In the
      patients with enhanced physiological tremor, we were unable to detect consistent
      significant corticomuscular coherences at the tremor frequency. INTERPRETATION:
      Using simultaneous EEG-EMG recordings, we showed that significant corticomuscular
      coherences at the tremor frequency can be found in essential tremor. This finding
      contrasts with a recent study based on MEG recordings. The results suggest that
      the sensorimotor cortex is involved in the generation of essential tremor, in a
      similar way to that previously shown in parkinsonian resting tremor.

PMID- 11229672
TI  - A case of sleeping and forgetting.

PMID- 11229673
TI  - Intralesional injection of herpes simplex virus 1716 in metastatic melanoma.
AB  - We have previously shown that avirulent but replication-competent herpes simplex
      virus (HSV) 1716 causes cell death in human melanoma cell lines in vitro and
      selectively replicates in melanoma tissue in nude mice. We now present a pilot
      study of intratumoral injection of HSV1716 into subcutaneous nodules of
      metastatic melanoma in five patients with stage 4 melanoma. Two patients each
      received one injection, two received two injections, and one received four
      injections of 10(3) plaque-forming units HSV1716. In one patient, flattening of
      previously palpable tumour nodules was seen 21 days after two direct injections
      of HSV1716, and in injected nodules from all three patients who received two or
      more injections there was microscopic evidence of tumour necrosis.
      Immunohistochemical staining of injected nodules revealed evidence of virus
      replication confined to tumour cells. These findings suggest that HSV1716 is non
      toxic and could be of therapeutic benefit in patients with metastatic melanoma.

PMID- 11229674
TI  - Controlled oxygen therapy and carbon dioxide retention during exacerbations of
      chronic obstructive pulmonary disease.
AB  - Hypoxaemic patients with exacerbations of chronic obstructive pulmonary disease
      (COPD) are at some risk of carbon dioxide (CO2) retention during oxygen therapy.
      We quantified the risk of CO2 retention with oxygen therapy in COPD in 24
      consecutive patients presenting to the accident and emergency department with
      acute exacerbations associated with hypercapnic respiratory failure (partial
      arterial pressure of oxygen [PaO2] < 8 kPa and partial pressure of CO2 [PaCO2] >
      or = 6.5 kPa). Only three patients developed clinically important CO2 retention
      (defined as a rise in PaCO2 > 1 kPa) with controlled oxygen therapy (24-40% by
      Venturi mask to maintain the oxygen saturation at 91-92%). These patients
      presented with more severe hypercapnia, but all three required only low-flow
      oxygen (24-28%). These findings suggest only a small risk of aggravating
      hypercapnia with controlled oxygen supplementation.

PMID- 11229675
TI  - HBV-specific peptide associated with heat-shock protein gp96.
AB  - Glycoprotein 96 (gp96), a member of the heat-shock protein family, can elicit
      priming of antigen-specfic cytotoxic T lymphocytes, when bound to antigenic viral
      or tumour peptides. We used direct peptide isolation from purified gp96 and
      microsequencing to show that a virus-specific peptide is bound to gp96 derived
      from liver tissues of patients with hepatitis B virus (HBV)-induced
      hepatocellular carcinoma. This virus-specific peptide has potential for
      engineering tumour vaccines against hepatocellular carcinoma and chronic HBV
      infection.

PMID- 11229676
TI  - Development of spectral colour banding in cytogenetic analysis.
AB  - We developed a novel chromosome banding technique-spectral colour banding (SCAN).
      With this technique we displayed a multicolour banding pattern that almost
      entirely correlated with the corresponding G-banding pattern. With SCAN analysis
      we could identify the chromosome-band origin of double minute chromosomes in
      gastric cancer. Our preliminary use of this technique suggests that it has
      significant clinical applications for cytogenetic analysis.

PMID- 11229677
TI  - "Celera's method failed", says Human Genome Project.

PMID- 11229678
TI  - Cancer and the human genome: no quick fix.

PMID- 11229679
TI  - Behavioural genomics--where next?

PMID- 11229680
TI  - Ethical implications of research on the human genome.

PMID- 11229681
TI  - Caution marks prospects for exploiting the genome.

PMID- 11229682
TI  - A global role for the human genome.

PMID- 11229683
TI  - Who will win the Nobel Prize?

PMID- 11229685
TI  - In search of A Fortunate Man.

PMID- 11229684
TI  - Inflammation and cancer: back to Virchow?
AB  - The response of the body to a cancer is not a unique mechanism but has many
      parallels with inflammation and wound healing. This article reviews the links
      between cancer and inflammation and discusses the implications of these links for
      cancer prevention and treatment. We suggest that the inflammatory cells and
      cytokines found in tumours are more likely to contribute to tumour growth,
      progression, and immunosuppression than they are to mount an effective host
      antitumour response. Moreover cancer susceptibility and severity may be
      associated with functional polymorphisms of inflammatory cytokine genes, and
      deletion or inhibition of inflammatory cytokines inhibits development of
      experimental cancer. If genetic damage is the "match that lights the fire" of
      cancer, some types of inflammation may provide the "fuel that feeds the flames".
      Over the past ten years information about the cytokine and chemokine network has
      led to development of a range of cytokine/chemokine antagonists targeted at
      inflammatory and allergic diseases. The first of these to enter the clinic,
      tumour necrosis factor antagonists, have shown encouraging efficacy. In this
      article we have provided a rationale for the use of cytokine and chemokine
      blockade, and further investigation of non-steroidal anti-inflammatory drugs, in
      the chemoprevention and treatment of malignant diseases.

PMID- 11229686
TI  - The dystrophy of Duchenne.

PMID- 11229687
TI  - Travel and risk of venous thrombosis.

PMID- 11229688
TI  - Travel and risk of venous thrombosis.

PMID- 11229689
TI  - Travel and risk of venous thrombosis.

PMID- 11229690
TI  - Travel and risk of venous thrombosis.

PMID- 11229691
TI  - Travel and risk of venous thrombosis.

PMID- 11229692
TI  - Travel and risk of venous thrombosis.

PMID- 11229693
TI  - Cancer survival.

PMID- 11229694
TI  - Caesarean section and litigation.

PMID- 11229695
TI  - Fetal death and radiation exposure.

PMID- 11229696
TI  - Hepatitis C detection.

PMID- 11229697
TI  - Melatonin secretion after surgery.

PMID- 11229698
TI  - Postoperative nitric oxide.

PMID- 11229699
TI  - Helium/oxygen and severe COPD.

PMID- 11229700
TI  - Malaria eradication on islands.

PMID- 11229701
TI  - Risk score for treatment of upper-gastrointestinal haemorrhage.

PMID- 11229702
TI  - Adverse drug reactions.

PMID- 11229703
TI  - Adverse drug reactions.

PMID- 11229704
TI  - Adverse drug reactions.

PMID- 11229705
TI  - Myalgic encephalomyelitis in children.

PMID- 11229706
TI  - The relation between acute physiological variables and outcome on the Glasgow
      Outcome Scale and Disability Rating Scale following severe traumatic brain
      injury.
AB  - The relation between outcome and duration of adverse physiological events was
      studied, using suggested critical physiological values. Subjects were 184
      patients with severe traumatic brain injury who received continuous monitoring of
      intracranial pressure (ICP), mean arterial pressure (MAP), cerebral perfusion
      pressure (CPP), and jugular venous oxygen saturation. Longer durations of adverse
      physiological events were significantly related to Glasgow Outcome Scale (GOS)
      scores and Disability Rating Scale (DRS) scores for all variables at all
      timepoints postinjury. When analyses excluded patients who died, the relation
      between adverse physiological events and GOS was nonsignificant; however,
      duration of ICP, MAP, and CPP still accounted for a significant portion of the
      variance in DRS scalres. The relative sensitivity of the GOS and DRS is
      discussed.

PMID- 11229707
TI  - Functional status examination: a new instrument for assessing outcome in
      traumatic brain injury.
AB  - The Functional Status Examination (FSE) is a new measure designed to evaluate
      change in activities of everyday life as a function of an event or illness,
      including traumatic brain injury. The measure covers physical, social, and
      psychological domains. The FSE is based on a structured interview and includes
      levels of functioning that accommodate the full spectrum of possible outcomes,
      from death through recovery to preinjury functioning. Based on 133 prospectively
      studied patients with moderate to severe traumatic brain injury, the FSE has
      favorable psychometric properties including good test-retest reliability (r =
      0.80) and close correspondence of assessments provided by the patient and their
      significant other (SO; r = 0.80). The FSE correlated significantly with each of
      three severity indices with closest relationships occurring between the FSE
      assessed by the SO and posttraumatic amnesia (r = 0.76). The FSE assessed by the
      SO was significantly (p < 0.05) more closely related to each severity index than
      the Glasgow Outcome Scale (GOS) or Sickness Impact Profile and, for two of the
      three indices, than the SF-36. All measures showed significant change from 1 to 6
      months after injury with the FSE showing the largest effect sizes. The FSE is
      significantly related to important constructs such as family burden, SO
      depression, and sacrifices the family makes, as well as overall indices of
      recovery and satisfaction with level of functioning. The latter relationships are
      significantly stronger than for the GOS. The FSE has demonstrated good
      reliability, validity, and sensitivity, and appears to be a promising instrument
      for monitoring recovery and assessing functional status in clinical trials.

PMID- 11229708
TI  - Age-dependency of 45calcium accumulation following lateral fluid percussion:
      acute and delayed patterns.
AB  - This study was designed to determine the regional and temporal profile of
      45calcium (45Ca2+) accumulation following mild lateral fluid percussion (LFP)
      injury and how this profile differs when traumatic brain injury occurs early in
      life. Thirty-six postnatal day (P) 17, thirty-four P28, and 17 adult rats were
      subjected to a mild (approximately 2.75 atm) LFP or sham injury and processed for
      45Ca2+ autoradiography immediately, 6 h, and 1, 2, 4, 7, and 14 days after
      injury. Optical densities were measured bilaterally within 16 regions of
      interest. 45Ca2+ accumulation was evident diffusely within the ipsilateral
      cerebral cortex immediately after injury (18-64% increase) in all ages, returning
      to sham levels by 2-4 days in P17s, 1 day in P28s, and 4 days in adults. While
      P17s showed no further 45Ca2+ accumulation, P28 and adult rats showed an
      additional delayed, focal accumulation in the ipsilateral thalamus beginning 2-4
      days postinjury (12-49% increase) and progressing out to 14 days (26-64%
      increase). Histological analysis of cresyl violet-stained, fresh frozen tissue
      indicated little evidence of neuronal loss acutely (in all ages), but
      considerable delayed cell death in the ipsilateral thalamus of the P28 and adult
      animals. These data suggest that two temporal patterns of 45Ca2+ accumulation
      exist following LFP: acute, diffuse calcium flux associated with the injury
      induced ionic cascade and blood brain barrier breakdown and delayed, focal
      calcium accumulation associated with secondary cell death. The age-dependency of
      posttraumatic 45Ca2+ accumulation may be attributed to differential biomechanical
      consequences of the LFP injury and/or the presence or lack of secondary cell
      death.

PMID- 11229709
TI  - Brain oxygen tension, oxygen supply, and oxygen consumption during arterial
      hyperoxia in a model of progressive cerebral ischemia.
AB  - We investigated the changes in brain oxygen tension (ptiO2) after ventilation
      with pure O2 in order to (1) clarify the pathophysiology of O2 exchange in the
      cerebral microcirculation; and (2) investigate the relationship between brain O2
      tension, O2 delivery, and consumption in steady-state conditions during stepwise
      cerebral blood flow (CBF) reductions. A swine model was developed to reduce CBF
      in three stable steps: (1) baseline (CBF 100%), (2) CBF of 50-60% of baseline,
      and (3) CBF of <30% of baseline. CBF was reduced by infusing saline into the left
      lateral ventricle through a catheter connected with an infusion pump. At each
      step, hyperoxia was tested by increasing the inspired oxygen fraction up to 100%,
      PtiO2 reflected the CBF reductions, since it was respectively 27.95 (+/-10.15),
      14.77 (+/-3.58), and 3.45 (+/-2.89) mm Hg during the three CBF steps. Hyperoxia
      was followed by an increase in ptiO2, although the increase was significantly
      lower when hyperoxia was applied during progressive ischemia. O2 supply to the
      brain did not change during hyperoxia. Arteriovenous oxygen difference (AVDO2)
      decreased during the phases of intact CBF and moderate impairment, but not during
      the phase of severe CBF reduction. In conclusion, ptiO2 reductions closely
      reflect the imbalance between oxygen delivery and demand; this implies a link
      between low ptiO2 and defective O2 supply due to impaired CBF. However, this
      relation is not necessarily reciprocal, since manipulating brain oxygen tension
      does not always influence brain oxygen delivery, as in the case of ventilation
      with pure oxygen.

PMID- 11229710
TI  - Injury severity and sensitivity to treatment after controlled cortical impact in
      rats.
AB  - We sought to determine sensitivity of the cortical impact injury model of
      traumatic brain injury (TBI) to severity of injury and to treatment. We examined
      the pattern of motor and cognitive deficits and recovery following TBI over a
      range of injury severities, and examined the efficacy of surface-induced moderate
      hypothermia at three disparate injury levels. In experiment I, Sprague-Dawley
      rats were injured at one of eight injury severity levels from 0 mm (sham) to 2.5
      mm depth of penetration. On postinjury day 1, balance beam, rotorod performance,
      and posture reflexes were evaluated. Motor outcome was increasingly impaired with
      increasing injury levels, with the pattern of deficits showing a step-like
      function. Cognitive deficits, assessed using water maze on day 7, were more
      severe for the 2.5-mm group than for the 1.6-mm injury group, while the 1.0-mm
      group did not differ from the sham controls. In experiments II-IV, hypothermia,
      30 degrees C for 3-h duration or normothermia was applied to three injury levels:
      1.0 mm, the least cortical deformation; 2.5 mm, the most deformation; and 1.6 mm,
      representing a level in-between. Neurologic outcome was assessed relative to
      shams on postinjury days 1, 3, and 5. The 1.0-mm group exhibited small deficits
      that recovered completely by day 3; the 1.6-mm group recovered to the level of
      shams by day 5, and the 2.5-mm group did not show significant recovery during the
      testing period. Hypothermia effectively attenuated behavioral deficits for the
      1.6-mm group, but had no effect on the other two groups. These three observations
      -that increasing injury severity is associated with increasing motor and
      cognitive deficits, that injury severity is related to recovery time, and that
      hypothermia treatment is selectively effective--have each been reported in the
      human TBI population; thus, moderate cortical impact injury in rats may be a
      model with clinical predictability for evaluating neuroprotective therapies.

PMID- 11229711
TI  - Automated quantitative gait analysis during overground locomotion in the rat: its
      application to spinal cord contusion and transection injuries.
AB  - Analysis of locomotion is an important tool in the study of peripheral and
      central nervous system damage. Most locomotor scoring systems in rodents are
      based either upon open field locomotion assessment, for example, the BBB score or
      upon foot print analysis. The former yields a semiquantitative description of
      locomotion as a whole, whereas the latter generates quantitative data on several
      selected gait parameters. In this paper, we describe the use of a newly developed
      gait analysis method that allows easy quantitation of a large number of
      locomotion parameters during walkway crossing. We were able to extract data on
      interlimb coordination, swing duration, paw print areas (total over stance, and
      at 20-msec time resolution), stride length, and base of support: Similar data can
      not be gathered by any single previously described method. We compare changes in
      gait parameters induced by two different models of spinal cord injury in rats,
      transection of the dorsal half of the spinal cord and spinal cord contusion
      injury induced by the NYU or MASCIS device. Although we applied this method to
      rats with spinal cord injury, the usefulness of this method is not limited to
      rats or to the investigation of spinal cord injuries alone.

PMID- 11229712
TI  - Effects of enriched housing on functional recovery after spinal cord contusive
      injury in the adult rat.
AB  - To date, most research performed in the area of spinal cord injury focuses on
      treatments designed to either prevent spreading lesion (secondary injury) or to
      enhance outgrowth of long descending and ascending fiber tracts around or through
      the lesion. In the last decade, however, several authors have shown that it is
      possible to enhance locomotor function after spinal cord injury in both animals
      and patients using specific training paradigms. As a first step towards combining
      such training paradigms with pharmacotherapy, we evaluated recovery of function
      in adult rats sustaining a spinal cord contusion injury (MASCIS device, 12.5 mm
      at T8), either housed in an enriched environment or in standard cages (n = 15 in
      both groups). The animals in the enriched environment were stimulated to increase
      their locomotor activity by placing water and food on opposite sides of the cage.
      As extra stimuli, a running wheel and several other objects were added to the
      cage. We show that exposure to the enriched environment improves gross and fine
      locomotor recovery as measured by the Basso, Beattie, and Bresnahan (BBB)
      locomotor rating scale, the BBB subscale, the Gridwalk, and the Thoracolumbar
      height test. However, no group differences were found on our electrophysiological
      parameters nor on the amount of spared white matter. These data justify further
      studies on enriched housing and more controlled exercise training, with their use
      as potential additive to pharmacological intervention.

PMID- 11229713
TI  - FK506 rescues peripheral nerve allografts in acute rejection.
AB  - This study investigated the ability of the immunosuppressant FK506 to reverse
      nerve allograft rejection in progress. Eighty-four Buffalo rats received
      posterior tibial nerve grafts from either Lewis or Buffalo donor animals.
      Allografts were left untreated for either 7, 10, or 14 days before receiving
      daily subcutaneous FK506 injections (2 mg/kg). Time-matched control animals
      received either an isograft, an allograft with continuous FK506, or an allograft
      with no postoperative FK506 therapy. All animals underwent weekly evaluation of
      nerve function by walking track analysis. Experimental group animals were
      sacrificed either immediately prior to initiation of FK506 therapy (days 7, 10,
      or 14), after 2 weeks of immunosuppressive treatment, or 8 weeks postsurgery.
      Histomorphometric analysis, consisting of measurements of total number of nerve
      fibers, neural density, and percent of neural debris, demonstrated a
      statistically significant increase in regeneration in the isograft group relative
      to the untreated allograft group within 28 days of transplantation. Grafts
      harvested from animals receiving 2 weeks of FK506 after 7 or 10 days of rejection
      were histomorphometrically similar to time-matched isografts. By contrast, grafts
      from animals receiving 2 weeks of FK506 following 14 days without therapy
      resembled untreated allografts and demonstrated significant histomorphometric
      differences from isografts at the corresponding time point. Analysis of walking
      track data confirmed that relative to untreated allografts, functional recovery
      was hastened in animals receiving an isograft, or allograft treated with FK506.
      This study demonstrated that when started within 10 days of graft placement,
      FK506 could reverse nerve allograft rejection in rats evaluated following 2 weeks
      of treatment.

PMID- 11229714
TI  - A model to determine the initial phase space of a clinical electron beam from
      measured beam data.
AB  - Advanced electron beam dose calculation models for radiation oncology require as
      input an initial phase space (IPS) that describes a clinical electron beam. The
      IPS is a distribution in position, energy and direction of electrons and photons
      in a plane in front of the patient. A method is presented to derive the IPS of a
      clinical electron beam from a limited set of measured beam data. The electron
      beam is modelled by a sum of four beam components: a main diverging beam,
      applicator edge scatter, applicator transmission and a second diverging beam. The
      two diverging beam components are described by weighted sums of monoenergetic
      diverging electron and photon beams. The weight factors of these monoenergetic
      beams are determined by the method of simulated annealing such that a best fit is
      obtained with depth-dose curves measured for several field sizes at two source
      surface distances. The resulting IPSs are applied by the phase-space evolution
      electron beam dose calculation model to calculate absolute 3D dose distributions.
      The accuracy of the calculated results is in general within 1.5% or 1.5 mm; worst
      cases show differences of up to 3% or 3 mm. The method presented here to describe
      clinical electron beams yields accurate results, requires only a limited set of
      measurements and might be considered as an alternative to the use of Monte Carlo
      methods to generate full initial phase spaces.

PMID- 11229715
TI  - Incorporating dynamic collimator motion in Monte Carlo simulations: an
      application in modelling a dynamic wedge.
AB  - In radiation therapy, new treatment modalities employing dynamic collimation and
      intensity modulation increase the complexity of dose calculation because a new
      dimension, time, has to be incorporated into the traditional three-dimensional
      problem. In this work, we investigated two classes of sampling technique to
      incorporate dynamic collimator motion in Monte Carlo simulation. The methods were
      initially evaluated for modelling enhanced dynamic wedges (EDWs) from Varian
      accelerators (Varian Medical Systems, Palo Alto, USA). In the position
      probability-sampling or PPS method, a cumulative probability distribution
      function (CPDF) was computed for the collimator position, which could then be
      sampled during simulations. In the static-component-simulation or SCS method, a
      dynamic field is approximated by multiple static fields in a step-shoot fashion.
      The weights of the particles or the number of particles simulated for each
      component field are computed from the probability distribution function (PDF) of
      the collimator position. The CPDF and PDF were computed from the segmented
      treatment tables (STTs) for the EDWs. An output correction factor had to be
      applied in this calculation to account for the backscattered radiation affecting
      monitor chamber readings. Comparison of the phase-space data from the PPS method
      (with the step-shoot motion) with those from the SCS method showed excellent
      agreement. The accuracy of the PPS method was further verified from the agreement
      between the measured and calculated dose distributions. Compared to the SCS
      method, the PPS method is more automated and efficient from an operational point
      of view. The principle of the PPS method can be extended to simulate other
      dynamic motions, and in particular, intensity-modulated beams using multileaf
      collimators.

PMID- 11229716
TI  - An iterative sequential mixed-integer approach to automated prostate
      brachytherapy treatment plan optimization.
AB  - Conventional treatment planning for interstitial prostate brachytherapy is
      generally a 'trial and error' process in which improved treatment plans are
      generated by iteratively changing, via expert judgement, the configuration of
      sources within the target volume in order to achieve a satisfactory dose
      distribution. We have utilized linear mixed-integer programming (MIP) and the
      branch-and-bound method, a deterministic search algorithm, to generate treatment
      plans. The rapidity of dose falloff from an interstitial radioactive source
      requires fine sampling of the space in which dose is calculated. This leads to a
      large and complex model that is difficult to solve as a single 3D problem. We
      have therefore implemented an iterative sequential approach that optimizes pseudo
      independent 2D slices to achieve a fine-grid 3D solution. Using our approach,
      treatment plans can be generated in 20-45 min on a 200 MHz processor. A
      comparison of our approach with the manual 'trial and error' approach shows that
      the optimized plans are generally superior. The dose to the urethra and rectum is
      usually maintained below harmful levels without sacrificing target coverage. In
      the event that the dose to the urethra is undesirably high, we present a refined
      optimization approach that lowers urethra dose without significant loss in target
      coverage. An analysis of the sensitivity of the optimized plans to seed
      misplacement during the implantation process is also presented that indicates
      remarkable stability of the dose distribution in comparison with manual treatment
      plans.

PMID- 11229717
TI  - Transit dose of an Ir-192 high dose rate brachytherapy stepping source.
AB  - Clinical dosimetry for high dose rate (HDR) brachytherapy with a single stepping
      source generally neglects the transit dose. This study investigates the effects
      of the transit dose in the target volume of an HDR brachytherapy stepping source.
      A video method was used to analyse the entrance, exit and the interdwell transit
      speed of the source for different path lengths and step sizes ranging from 2.5 mm
      to 995 mm. The transit speed was found to vary with the step size and path
      length. For the travelled distances of 2.5, 5.0, 10.0, 230 and 995 mm, the
      average transit speeds were 54, 72, 233, 385 and 467 mm s(-1) respectively. The
      results also show that the manufacturer has attempted to compensate for the
      effects of interdwell transit dose by reducing the actual dwell time of the
      source. A well-type chamber was used to determine the dose differences between
      two sets of measurements, one being the stationary dose only and the other being
      the sum of stationary and transit doses. Single catheters of active lengths of 20
      and 40 mm, different dwell times of 0.5, 1, 2 and 5 s and different step sizes of
      2.5, 5 and 10 mm were used in the measurements with the well-type chamber. Most
      of the measured dose differences between stationary and stationary plus
      interdwell source movement were within 2%. The additional dose due to the source
      transit can be as high as 24.9% for the case of 0.5 s dwell time, 10 mm step size
      and 20 mm active length. The dose difference is mainly due to the entrance and
      exit source movement but not the interdwell movement.

PMID- 11229719
TI  - Segmental cardiac function computed from ECG-gated SPECT images through solution
      of equations of continuity for fluids.
AB  - Segmental contractions were quantified from images of electrocardiographic-gated
      single-photon emission computed tomography. Counts were integrated in 64 angles
      about the centre on short-axis images and projected onto a cylindrical screen.
      Changes in the projected count were shown to obey the equation of continuity for
      two-dimensional fluids (the Poisson equation). Displacements of each pixel point
      were calculated from the velocity field to quantify the amount of dislocation.
      Changes in the configuration of the pixel points were projected back on the
      cardiac wall, and finally segmental contractions were evaluated as a percentage
      reduction of the area. Computer simulations were performed for numerical models
      of circumferential and long-axial contractions, uneven eccentric contractions and
      rotations. These models were blurred with a three-dimensional Gaussian function.
      The results obtained using this method (quantification of segmental function by
      solving the Poisson equation (QSFP)) were compared with the wall-thickening
      method (WTM) and the maximum-count method. Both QSFP and WTM yielded good
      agreement with predicted values for circumferential and long-axial contractions.
      Only QSFP gave satisfactory results for uneven eccentric contractions, and
      rotation models. QSFP should provide a useful tool for in vivo quantification of
      contraction tangential to the cardiac wall by eliminating errors due to
      displacements.

PMID- 11229720
TI  - A diffusion theory model of spatially resolved fluorescence from depth-dependent
      fluorophore concentrations.
AB  - A photon diffusion model has been developed to calculate the steady-state
      spatially resolved fluorescence from pencil beam excitation in layered tissue.
      The model allows the calculation of both the excitation reflectance and the
      fluorescence escape for an arbitrary continuous depth distribution of tissue
      optical properties and fluorophore concentration. The validity of this model was
      verified by comparison with Monte Carlo simulations and experimental measurements
      using phantoms with tissue-like optical properties. The potential usefulness of
      the spatially resolved fluorescence was explored using the model and simulations
      of realistic drug distributions. It was shown that using this technique it may be
      possible to quantify the diffusion of a topically administered drug into the
      skin, or the photobleaching of a sensitizer during photodynamic therapy.

PMID- 11229718
TI  - An automated dosimetry system for testing whole-body ultraviolet phototherapy
      cabinets.
AB  - A new technique is described for automated ultraviolet dosimetry within whole
      body phototherapy cabinets. A dual-head detector system has been designed,
      permitting simultaneous assessment of irradiance levels and radiant intensities
      from individual lamps. One detector is used in combination with a diffuser/filter
      system for the measurement of irradiance and the other is mounted at the end of a
      slit collimator to provide a measurement which can be related to the radiant
      intensities of the individual lamps. These quantities are derived from 800
      separate measurements made during rotation of the detector head around a 360
      degrees circle at a fixed height and position within the cabinet under remote
      computer software control. The device has advantages compared with standard
      techniques, enabling measurements to be made without the need for a person to be
      present in the cabinet. A full set of measurements is made with minimal switching
      of the power supply to the lamps. This simplifies the assessment and reduces the
      uncertainty from variation in output after the lamps are switched on. Variations
      in irradiance with orientation for the smaller phototherapy cabinets are clearly
      demonstrated. Plots of data from the collimated detector show peaks corresponding
      to the lamps and the surrounding reflectors. The plots enable failed lamps to be
      detected and peak values can be related to radiant intensities of individual
      lamps.

PMID- 11229721
TI  - Experimental examination of a targeted hyperthermia system using inductively
      heated ferromagnetic microspheres in rabbit kidney.
AB  - It is known that significant heating can be generated by magnetic hysteresis
      effects in small ferromagnetic particles exposed to a rapidly alternating
      magnetic field. If such particles can be made to infiltrate the vascular bed
      surrounding a tumour by intravascular infusion then it may be possible to
      generate sufficient heating to destroy the tumour by hyperthermia. One of the
      constraints on such a technique is the limited amount of magnetic material that
      can be delivered to a tumour via the intravascular route and the consequent
      heating that can be induced by this material. Here, we report on a series of
      experiments in which doses of microspheres containing different amounts of
      ferromagnetic material were infused into rabbit kidneys via the renal artery with
      the aim of testing whether adequate tissue heating could be achieved using
      realistic concentrations of the embolised material. Heating rates were measured
      for each infused quantity under similar conditions with the animal alive and dead
      to examine the role of blood flow in the heating process. The results show that
      tissue temperatures above the therapeutic threshold of 42 degrees C can be
      readily achieved using this method with clinically relevant concentrations of
      microspheres in living tissue.

PMID- 11229722
TI  - Calibrated electro-optic E-field sensors for hyperthermia applications.
AB  - E-field measurements are an important task for the investigation of newly
      developed hyperthermia applicators as well as for online control of hyperthermia
      treatments. Compact and non-perturbing integrated optical E-field sensors based
      on LiNbO3 as well as optical E-field sensors based on infrared emitting diodes
      and light bulbs are suitable for nearfield measurements of hyperthermia antennas.
      In order to investigate their properties a calibration cell with transverse
      electromagnetic (TEM) waves has been constructed. By using this cell, calibration
      curves and directional patterns for all sensors have been measured. Due to the
      threshold behaviour of the IRED and light bulb sensor, only the LiNbO3 sensor is
      capable of measuring weak fields inside an applicator or a homogeneous phantom.

PMID- 11229723
TI  - Mechanical haemolysis in shock wave lithotripsy (SWL): I. Analysis of cell
      deformation due to SWL flow-fields.
AB  - This work analyses the interaction of red blood cells (RBCs) with shock-induced
      and bubble-induced flows in shock wave lithotripsy (SWL), and calculates, in
      vitro, the lytic effects of these two flows. A well known experimentally observed
      fact about RBC membranes is that the lipid bilayer disrupts when subjected to an
      areal strain (deltaA/A)c of 3%, and a corresponding, critical, isotropic tension,
      Tc, of 10 mN m(-1) (1 mN m(-1) = 1 dyne cm(-1)). RBCs suspended in a fluid medium
      tend to deform in accordance with the deformation of the surrounding fluid
      medium. The fluid flow-field is lytically effective if the membrane deformation
      exceeds the above threshold value. From kinematic analysis, motion of an
      elementary fluid particle can always be decomposed into a uniform translation, an
      extensional flow (e.g. -->uinfinity(x, y, z) = (k(t)x, -k(t)y, 0)) along three
      mutually perpendicular axes, and a rigid rotation of these axes. However, only an
      extensional flow causes deformation of a fluid particle, and consequently deforms
      the RBC membrane. In SWL, a fluid flow-field, induced by a non-uniform shock
      wave, as well as radial expansion/implosion of a bubble, has been hypothesized to
      cause lysis of cells. Both the above flow-fields constitute an unsteady,
      extensional flow, which exerts inertial as well as viscous forces on the RBC
      membrane. The transient inertial force (expressed as a tension, or force/length),
      is given by Tiner approximately rhor(c)3k/tau, where tau is a timescale of the
      transient flow and r(c) is a characteristic cell size. When the membrane is
      deformed due to inertial effects, membrane strain is given by deltaA/A
      approximately ktau. The transient viscous force is given by Tvisc approximately
      rho(nu/tau)1/2r(c)2k, where rho and nu are the fluid density and kinematic
      viscosity. For the non-uniform shock, the extensional flow exerts an inertial
      force, Tiner approximately 64 mN m(-1), for a duration of 3 ns, sufficient to
      induce pores in the RBC membrane. For a radial flow-field, induced by bubble
      expansion/implosion, the inertial forces are of a magnitude 100 mN m(-1), which
      last for a duration of 1 micros, sufficient to cause rupture. Bubble-induced
      radial flow is predicted to be lytically more effective than shock-induced flow
      in typical in vitro experimental conditions.

PMID- 11229724
TI  - A representation of an NTCP function for local complication mechanisms.
AB  - A mathematical formalism was tailored for the description of mechanisms
      complicating radiation therapy with a predominantly local component. The
      functional representation of an NTCP function was developed based on the notion
      that it has to be robust against population averages in order to be applicable to
      experimental data. The model was required to be invariant under scaling
      operations of the dose and the irradiated volume. The NTCP function was derived
      from the model assumptions that the complication is a consequence of local tissue
      damage and that the probability of local damage in a small reference volume is
      independent of the neighbouring volumes. The performance of the model was
      demonstrated with an animal model which has been published previously (Powers et
      al 1998 Radiother. Oncol. 46 297-306).

PMID- 11229725
TI  - Dose resolution in radiotherapy polymer gel dosimetry: effect of echo spacing in
      MRI pulse sequence.
AB  - In polymer gel dosimetry using magnetic resonance imaging, the uncertainty in
      absorbed dose is dependent on the experimental determination of T2. The concept
      of dose resolution (Dpdelta) of polymer gel dosimeters is developed and applied
      to the uncertainty in dose related to the uncertainty in T2 from a range of T4
      encountered in polymer gel dosimetry. Dpdelta is defined as the minimal
      separation between two absorbed doses such that they may be distinguished with a
      given level of confidence, p. The minimum detectable dose (MDD) is Dpdelta as the
      dose approaches zero. Dpdelta and the minimum detectable dose both give a
      quantifiable indication of the likely practical limitations and usefulness of the
      dosimeter. Dpdelta of a polyacrylamide polymer gel dosimeter is presented for
      customized 32-echo and standard multiple-spin-echo sequences on a clinical MRI
      scanner. In evaluating uncertainties in T2, a parameter of particular
      significance in the pulse sequence is the echo spacing (ES). For optimal results,
      ES should be selected to minimize Dpdelta over a range of doses of interest in
      polymer gel dosimetry.

PMID- 11229726
TI  - Response charactterization of ammonium tartrate solid state pellets for ESR
      dosimetry with radiotherapeutic photon and electron beams.
AB  - Solid state pellets (1 mm thick) for electron spin resonance (ESR) dosimetry were
      made using ammonium tartrate as the radiation-sensitive substance. Their
      behaviour was experimentally investigated as a function of dose with 60Co gamma
      rays. The calibration function obtained permits measurements of absorbed dose in
      the 2-50 Gy range, with a combined uncertainty of +/-4%. The lowest detectable
      dose was about 0.5 Gy. These properties are comparable with or even better than
      those of ESR dosimeters made from other materials. The time stability of the ESR
      signal of ammonium tartrate dosimeters at different storage conditions after
      irradiation was studied. A rather complex behaviour was observed, which suggests
      that more species of free radicals are produced by radiation and that migration
      processes may be effective. No dependence of the response on beam quality was
      found for high-energy photon and electron beams produced by a linear accelerator
      used in radiotherapy, whereas dose was underestimated with low-energy x-rays.

PMID- 11229727
TI  - Dosimetry of low-energy protons and light ions.
AB  - For the vertical beam facility at the 14 MV Munich tandem accelerator, various
      techniques for dosimetry were tested for radiation fields of low-energy protons
      and light ions (4He, 12C and 16O). A reference dose was determined from the
      fluence of particles by counting individual particles. A parallel-plate Markus
      chamber with a small sensitive air volume was used for beam dosimetry applying
      the ICRU protocol. The doses measured with the ionization chamber were compared
      with doses evaluated from the fluence measurements. Alternative dose measurements
      were performed using MTS-N LiF:Mg, Ti thermoluminescence detectors (TLDs) and a
      photometrically evaluated Fricke chemical dosimeter. An uncertainty of 8% was
      found in the determination of the dose relative to the reference method. Effects
      of an inhomogeneous energy loss and a finite track length of the projectiles in
      the sensitive detector volume of the dosimeters had to be taken into account.

PMID- 11229728
TI  - Tumour dosimetry in human liver following hepatic yttrium-90 microsphere therapy.
AB  - Radiation dose distributions arising from intrahepatic arterial infusion of 90Y
      microspheres have been investigated. Tissue samples from normal liver, the tumour
      periphery and tumour centre were taken from a patient following infusion of 3 GBq
      of 32 microm diameter resin microspheres labelled with 90Y as treatment for an 80
      mm diameter metastatic liver tumour. The measured microsphere distributions in
      three dimensions were used to calculate radiation dose patterns. Although
      microspheres concentrated in the tumour periphery, heterogeneous doses were
      delivered to all tissues. Within the tumour periphery average doses ranged from
      200 Gy to 600 Gy with minimum doses between 70 Gy and 190 Gy. The average and
      minimum doses for the tumour centre sample were 6.8 Gy and 3.7 Gy respectively.
      In the normal liver sample the average dose was 8.9 Gy with a minimum dose of 5
      Gy. Less than 1% of the normal liver tissue volume received more than 30 Gy, the
      level above which complications have resulted for whole liver exposure using
      external beam radiotherapy. These calculations suggest that preferential
      deposition of microspheres in the well-vascularized periphery of large tumours
      will lead to a high proportion of the tumour volume receiving a therapeutic dose,
      with most of the normal liver tissue being spared substantial damage.

PMID- 11229729
TI  - Dosimetry of 192Ir sources used for endovascular brachytherapy.
AB  - An in-phantom calibration technique for 192Ir sources used for endovascular
      brachytherapy is presented. Three different source lengths were investigated. The
      calibration was performed in a solid phantom using a Farmer-type ionization
      chamber at source to detector distances ranging from 1 cm to 5 cm. The dosimetry
      protocol for medium-energy x-rays extended with a volume-averaging correction
      factor was used to convert the chamber reading to dose to water. The air kerma
      strength of the sources was determined as well. EGS4 Monte Carlo calculations
      were performed to determine the depth dose distribution at distances ranging from
      0.6 mm to 10 cm from the source centre. In this way we were able to convert the
      absolute dose rate at 1 cm distance to the reference point chosen at 2 mm
      distance. The Monte Carlo results were confirmed by radiochromic film
      measurements, performed with a double-exposure technique. The dwell times to
      deliver a dose of 14 Gy at the reference point were determined and compared with
      results given by the source supplier (CORDIS). They determined the dwell times
      from a Sievert integration technique based on the source activity. The results
      from both methods agreed to within 2% for the 12 sources that were evaluated. A
      Visual Basic routine that superimposes dose distributions, based on the Monte
      Carlo calculations and the in-phantom calibration, onto intravascular ultrasound
      images is presented. This routine can be used as an online treatment planning
      program.

PMID- 11229730
TI  - Measurement of the response of Gd2O2S:Tb phosphor to 6 MV x-rays.
AB  - The phosphor GdO2S:Tb is widely used in camera-based electronic portal imaging
      devices (EPIDs). There is considerable interest in the application of EPIDs to
      dosimetry and the verification of intensity modulated radiation therapy produced
      by dynamic multileaf collimation (DMLC). This paper presents direct measurement
      of Gd2O2S:Tb phosphor luminescence under 6 MV x-ray irradiation from a linear
      accelerator using a photomultiplier tube. The luminescence following each
      radiation pulse (3 micros duration) was observed to decay with a dominant
      lifetime of 558 micros. Using a specialized electrometer, the temporal variation
      of the optical signal has been compared with the dose rate incident on the
      phosphor measured using a semiconductor diode detector. Under dose rates typical
      of those used in the clinic (1.2 Gy min(-1) to the phosphor), measurements at
      beam-start confirmed that the optical signal is linear with dose per radiation
      pulse. Measurements at beam termination following phosphor doses up to 4.4 Gy
      showed no residual signal associated with long-lived luminescence (afterglow)
      from the phosphor above the noise level of the optical signal (0.17% standard
      deviation). This measurement demonstrates that afterglow from Gd2O2S:Tb is not of
      significance for its application to DMLC verification. Additionally, it was
      confirmed that the accelerator pulse repetition frequency has no effect on the
      optical signal from the phosphor in the range 25-400 Hz.

PMID- 11229732
TI  - The accuracy and reliability of a novel handheld dynamic indentation probe for
      analysing articular cartilage.
AB  - This study investigates the accuracy and reliability of a novel handheld
      indentation system designed to ascertain the dynamic biomechanical properties of
      articular cartilage. A series of standard elastomers were assessed with both the
      handheld indentation system and a bench-top dynamic indentation system to assess
      the accuracy of the instrument. Interoperator and intraoperator experiments were
      undertaken to investigate the reliability of the system when used by an
      individual operator and by five different operators. Intraclass coefficients
      (Rho) were derived using a random effects model. The system was then used to
      ascertain the topographical variation in the shear moduli and phase lag of
      articular cartilage across normal ovine tibial plateaux. The system was shown to
      be highly accurate (R2 = 0.97), and had excellent reliability when measuring the
      dynamic shear modulus of articular cartilage (interoperator Rho = 0.75,
      intraoperator Rho = 0.79). Measurement of static shear modulus was less reliable
      (interoperator Rho = 0.15, intraoperator Rho = 0.52), but may be improved by
      monitoring the load applied to the instrument by the operator. The instrument was
      used to differentiate between different regions of cartilage and generated a
      topographical map of an ovine tibial plateau. The cartilage located beneath the
      menisci was 200-500% stiffer than the cartilage that was not covered by the
      menisci, while the phase lag was almost constant (10+/-2 SD) over the entire
      tibial plateau. The system was shown to be an accurate and reliable tool for
      rapidly assessing the dynamic biomechanical properties of articular cartilage,
      while being small enough to be used arthroscopically.

PMID- 11229731
TI  - Low-angle X-ray scattering from lyophilized blood constituents.
AB  - The characteristic nature of low-angle x-ray scattering from biological samples
      and its dependence on molecular structure is a subject of increasing interest. In
      this work, low-angle x-ray scattering from lyophilized (freeze-dried) whole
      blood, haemoglobin (Hb), serum and red blood cell membranes is studied. The
      scattering profiles of these samples are found to be reproducible and
      characteristic. A number of characterization parameters are introduced, showing
      significant differences between the investigated samples. The sensitivity of the
      scattering profiles of whole blood, Hb and serum towards induced molecular level
      variations is examined after doses of gamma irradiation of 3, 6 and 9 Gy. The
      full width at half maximum (FWHM) of the second peak of scattering and the
      percentage ratio of amplitudes of the first and second peaks (I1/I2)% are found
      to be the parameters most sensitive to irradiation. For all irradiated samples,
      it is observed that the FWHM of the second peak is always greater than the
      control, while the ratio (I1/I2)% is always smaller than the control.

PMID- 11229733
TI  - Non-contact measurement of thermal diffusivity in tissue.
AB  - We demonstrate the application of an infrared (IR) imaging technique for non
      contact determination of thermal diffusivity in biological materials. The
      proposed method utilizes pulsed laser excitation to produce an initial three
      dimensional temperature distribution in tissue, and records IR images of
      subsequent heat diffusion. The theoretical model assumes that the time-dependent
      temperature increase following pulsed laser exposure is due to independent heat
      diffusion in longitudinal and lateral directions. A nonlinear least-squares
      algorithm is used to compute the lateral thermal point spread function from a
      pair of recorded IR images and to determine the thermal diffusivity of a test
      specimen. The recorded time-sequence of IR images is used to compute thermal
      diffusivity as a function of increasing time interval between two IR emission
      images. Experimental application of the method was demonstrated using tissue
      phantoms, ex vivo samples of hydrated cartilage and in vivo epidermis.

PMID- 11229734
TI  - Calibration of three-dimensional ultrasound images for image-guided radiation
      therapy.
AB  - A new technique of patient positioning for radiotherapy/radiosurgery of
      extracranial tumours using three-dimensional (3D) ultrasound images has been
      developed. The ultrasound probe position is tracked within the treatment room via
      infrared light emitting diodes (IRLEDs) attached to the probe. In order to
      retrieve the corresponding room position of the ultrasound image, we developed an
      initial ultrasound probe calibration technique for both 2D and 3D ultrasound
      systems. This technique is based on knowledge of points in both room and image
      coordinates. We first tested the performance of three algorithms in retrieving
      geometrical transformations using synthetic data with different noise levels.
      Closed form solution algorithms (singular value decomposition and Horn's
      quaternion algorithms) were shown to outperform the Hooke and Jeeves iterative
      algorithm in both speed and accuracy. Furthermore, these simulations show that
      for a random noise level of 2.5, 5, 7.5 and 10 mm, the number of points required
      for a transformation accuracy better than 1 mm is 25, 100, 200 and 500 points
      respectively. Finally, we verified the tracking accuracy of this system using a
      specially designed ultrasound phantom. Since ultrasound images have a high noise
      level, we designed an ultrasound phantom that provides a large number of points
      for the calibration. This tissue equivalent phantom is made of nylon wires, and
      its room position is optically tracked using IRLEDs. By obtaining multiple images
      through the nylon wires, the calibration technique uses an average of 300 points
      for 3D ultrasound volumes and 200 for 2D ultrasound images, and its stability is
      very good for both rotation (standard deviation: 0.4 degrees) and translation
      (standard deviation: 0.3 mm) transformations. After this initial calibration
      procedure, the position of any voxel in the ultrasound image volume can be
      determined in world space, thereby allowing real-time image guidance of
      therapeutic procedures. Finally, the overall tracking accuracy of our 3D
      ultrasound image-guided positioning system was measured to be on average 0.2 mm,
      0.9 mm and 0.6 mm for the AP, lateral and axial directions respectively.

PMID- 11229735
TI  - Use of high-frequency ultrasound imaging to improve delineation of anterior uveal
      melanoma for proton irradiation.
AB  - The aim of this study was to evaluate high-frequency ultrasound imaging (HFUI) as
      an aid in localizing anterior margins of tumours of the eye for proton therapy.
      Proton irradiation of ocular melanoma requires an accurate assessment of all
      tumour margins. The tumour is marked surgically by suturing to the sclera four or
      five tantalum rings on the borders of the tumour defined by transillumination. In
      order to evaluate the clinical usefulness of high-frequency ultrasound imaging,
      four and five rings were surgically placed in a patient with an iris/ciliary body
      melanoma and in a patient with ciliochoroidal melanoma using transillumination to
      localize the tumour margins. Subsequently margins were verified by HFUI. In the
      first patient, the distances between the rings and the limbus were measured using
      calipers during surgery and were compared with HFUI measurements and measurements
      from planning software. The distances were comparable within 0.5 mm. In the
      second patient the treatment was planned in two different ways using EYEPLAN
      software. In the first scenario the shape of the tumour and its relation to the
      rings were obtained from the surgeon's mapping, the fundus drawing using a
      transilluminating point light source, and the HFUI. In the second scenario, the
      shape of the tumour was deduced from the ring positions only. It was observed
      that the maximum difference between the tumour edge as seen on high-frequency
      ultrasound images and the rings was 2.6 mm. The tumour volume was underestimated
      by 39% when tumour shape was obtained from ring positions only. During the past
      year we have utilized HFUI in 18 patients having tumours involving the anterior
      segment of the eye, among which four were treated with proton therapy. In
      conclusion, we believe that high-frequency ultrasound imaging provides additional
      information with respect to the location of tumour margins in ciliary body and
      anterior uveal melanoma. Occult extension of the tumour within the ciliary body
      or posterior iris may not be appreciated by transillumination alone.

PMID- 11229736
TI  - On a possible mechanism for peripheral nerve stimulation during magnetic
      resonance imaging scans.
AB  - When patients undergo a magnetic resonance imaging scan, they are subject to both
      strong static and temporal magnetic fields. The temporal fields are designed to
      vary at each point in the region being imaged. This is achieved by the use of
      gradient coils. However, when the gradient coils are switched very rapidly, the
      strongly time-varying magnetic fields produced can be responsible for stimulating
      nerves in the peripheral regions of the body. This paper gives a somewhat novel
      explanation for this phenomenon. The physical mechanism suggested is supported by
      an illustrative theoretical calculation.

PMID- 11229737
TI  - B1 field homogeneity and SAR calculations for the birdcage coil.
AB  - The finite-difference time-domain (FDTD) method is used to model a birdcage
      resonator. All the coil components, including the wires, lumped capacitors and
      the source, are geometrically modelled together. As such, the coupling effects
      within the birdcage, including the interactions of coil, source and human head,
      are accurately computed. A study of the transverse magnetic (B1) field
      homogeneity and the specific absorption rate (SAR) is presented on an
      anatomically detailed human head model at 64 and 200 MHz representing 1.5 and 4.7
      T MRI systems respectively. Unlike that at 64 MHz, the B1 field distribution is
      found to be inhomogeneous at 200 MHz. Also, high local SAR values are observed in
      the tissue near the source due to the coupling between the source and the head at
      200 MHz.

PMID- 11229738
TI  - An ntcp formula for the series model with a Yaes-type functional subunit
      mechanism.
AB  - Yaes and Kalend have noted that if functional subunit size is determined by
      factors such as cell migration lengths or biochemical diffusion lengths, rather
      than by fixed anatomical boundaries, then the conventional series normal tissue
      complication probability (ntcp) model should be conceptually modified. Here a von
      Mises-type formula describing the ntcp for such a modified model is derived,
      using a methodology based on that of Feller.

PMID- 11229740
TI  - Impedance magnetocardiogram.
AB  - We have developed an impedance magnetocardiogram (IMCG) system to detect the
      change of magnetic field corresponding to changes in blood volume in the heart. A
      low magnetic field from the electrical activity of the human heart--the so-called
      magnetocardiogram (MCG)--can be simultaneously detected by using this system.
      Because the mechanical and electrical functions in the heart can be monitored by
      non-invasive and non-contact measurements, it is easy to observe the
      cardiovascular functions from an accurate sensor position. This system uses a
      technique to demodulate induced current in a subject. A flux-locked circuit of a
      superconducting quantum interference device has a wide frequency range (above 1
      MHz) because a constant current (40 kHz) is fed through the subject. It is shown
      for the first time that the system could measure IMCG signals at the same time as
      MCG signals.

PMID- 11229739
TI  - A method for controlling image acquisition in electronic portal imaging devices.
AB  - Certain types of camera-based electronic portal imaging devices (EPIDs) which
      initiate image acquisition based on sensing a change in video level have been
      observed to trigger unreliably at the beginning of dynamic multileaf collimation
      sequences. A simple, novel means of controlling image acquisition with an Elekta
      linear accelerator (Elekta Oncology Systems, Crawley, UK) is proposed which is
      based on illumination of a photodetector (ORP-12, Silonex Inc., Plattsburgh, NY,
      USA) by the electron gun of the accelerator. By incorporating a simple trigger
      circuit it is possible to derive a beam on/off status signal which changes at
      least 100 ms before any dose is measured by the accelerator. The status signal
      does not return to the beam-off state until all dose has been delivered and is
      suitable for accelerator pulse repetition frequencies of 50-400 Hz. The status
      signal is thus a reliable means of indicating the initiation and termination of
      radiation exposure, and thus controlling image acquisition of such EPIDs for this
      application.

PMID- 11229741
TI  - Experimental determination of the overall perturbation factor for the NACP
      chamber in electron beams for dmax < d < or = d80.
AB  - In electron beam dosimetry with an ionization chamber, a factor that corrects for
      the cavity perturbation of the medium, Prepl, and one to account for the
      disturbance due to the chamber wall material differing from the medium, Pwall,
      are required. The overall perturbation correction factor, p(q) = PreplPwall, has
      been introduced because of the difficulty in separately measuring these two
      components. An advantage of parallel-plate ionization chambers is that p(q) has
      been shown to be close to unity at dmax. However, many dosimetry applications
      require knowledge of the overall perturbation factor at depths greater than dmax.
      We determined p(q) for the NACP chamber at depths beyond dmax by intercomparing
      percentage depth dose measurements made with it with those obtained with a
      PTW/diamond detector for which p(q) was taken as unity at all the measurement
      depths. Data were obtained at depths corresponding to approximately the 90 and 80
      per cent of the dose maxima for 20, 16, 12 and 6 MeV incident electrons. The beam
      energy at depth, Ed, and the percentage depth-dose gradient varied from 1.4 to
      14.3 MeV and 0 to 5.8% mm(-1) respectively. Our results show that within the
      estimated uncertainty of 1.3%, p(q),NACP is unity over the range of energies and
      dose gradients studied.

PMID- 11229742
TI  - Synthesis and biological evaluation of DNA targeting flexible side-chain
      substituted beta-carboline derivatives.
AB  - A series of 3-substituted-beta-carboline derivatives was synthesized from L
      tryptophan. The intercalating binding mode of these compounds with DNA, the
      effects of the flexible alkylamine side chain on the intercalating ability and
      their antitumor activity were studied, which agreed well with the molecular
      modeling results.

PMID- 11229743
TI  - Photochemical N-demethylation of alkaloids.
AB  - Certain alkaloids were observed to undergo N-demethylation processes under
      photochemical conditions. Tropine, acetyltropine, tropinone, and atropine were
      cleanly N-demethylated upon treatment with tetraphenylporphin, oxygen, and light.
      Dextromethorphan also underwent a N-demethylation reaction, but reacted further
      to afford an imine. In contrast, 14-acyloxycodeinones underwent a photochemically
      induced tandem N-demethylation acyl migration.

PMID- 11229744
TI  - Synthesis and biological evaluation of novel amides of polyunsaturated fatty
      acids with dopamine.
AB  - New amides of different fatty acids from the C18, C20, and C22 series with
      dopamine were synthesized. Pharmacological characterization in binding assays
      with rat brain membrane preparations and in the 'tetrad' of cannabinoid
      behavioral tests showed that, for these compounds, cannabinoid-like activity was
      dependent on the fatty acid moiety. Our data demonstrate that polyenoic fatty
      acid amides with dopamine comprise a new family of synthetic cannabimimetics.

PMID- 11229745
TI  - Modified synthesis and antiangiogenic activity of linomide.
AB  - A modified procedure for the synthesis of Linomide is described. The synthesized
      drug was characterized and assessed for its in vivo antiangiogenic activity. In a
      murine angiogenesis assay Linomide treatment inhibited new blood vessel formation
      as documented by reduced microvessel area and blood volume.

PMID- 11229747
TI  - Synthesis of sialyl Lewis(x) mimics. Modifications of the 6-position of
      galactose.
AB  - Seven sLe(x) mimics where the -CH2OH group of the galactose moiety is replaced by
      -CH2NH3+, -CH2NHAc, -CH2NHBz, -CH2OSO3Na, -COONa and -CONH2 have been prepared
      and tested for their binding affinity to E-selectin.

PMID- 11229748
TI  - Synthesis and anticonvulsant activity of novel and potent 1-aryl-7,8
      methylenedioxy-1,2,3,5-tetrahydro-4H-2,3-benzodiazepin-4-ones.
AB  - The synthesis and anticonvulsant activity of 1-aryl-7,8-methylenedioxy-1,2,3,5
      tetrahydro-4H-2,3-benzodiazepin-4-(thi)ones (4a-d) and their 3-N-alkylcarbamoyl
      derivatives (4e-h) are reported. The new compounds possess marked anticonvulsant
      properties, comparable to those of the dehydro analogues 3 and higher than that
      of GYKI 52466 (1). Noteworthy, compound 4c shows a longer-lasting anticonvulsant
      activity. Electrophysiological experiments show that derivative 4c is less
      effective than 1 and 3c to reduce the KA-evoked currents in cerebellar granule
      neurons.

PMID- 11229746
TI  - First tricyclic oximino derivatives as 5-HT3 ligands.
AB  - The design and synthesis of a new type of 5-HT3 ligand with subnanomolar affinity
      are described. The O-dialkylaminoethyloximinothienopyrrolizine structure was
      deduced from molecular modeling studies by replacement of an amidine moiety by an
      oximino one.

PMID- 11229749
TI  - Beta-D-glycosylamidines: potent, selective, and easily accessible 1-glycosidase
      inhibitors.
AB  - Beta-D-glycosylamidines, in which a glycon is connected via an N-glycoside
      linkage with a substituted amidine (aglycon), were synthesized in two steps from
      the corresponding sugars and served as stable and potent beta-glycosidase
      inhibitors with high selectivity according to the glycon- and alpha, beta
      specificities of the enzymes.

PMID- 11229750
TI  - Protein phosphatase 1 catalyses the direct hydrolytic cleavage of phosphate
      monoester in a ternary complex mechanism.
AB  - The catalytic subunit of the Ser/Thr protein phosphatase 1 (PP1cat) hydrolyses N
      acetyl Arg-Arg-Ala-phosphoThr-Val-Ala (K(M) = 3.7 mM) in a reaction that is
      inhibited competitively by inorganic phosphate (Pi, Ki = 1.6 mM) but unaffected
      by the product peptide alcohol at concentrations up to 3 mM. The enzyme does not
      catalyse the incorporation of 18O-label from 18O-labelled water into Pi whether,
      or not, the product alcohol is present. The dephosphorylated product alcohol of
      phosphorylated histone. an alternative substrate for the enzyme, serves as a
      competitive inhibitor for phosphopeptide hydrolysis (Ki = 60 microM) and co
      mediates 18O-label exchange into Pi in a concentration-dependent manner (K(M) =
      64 microM). These results indicate that hydrolysis occurs through the direct
      attack of an activated water molecule on the phosphate ester moiety of the
      substrate in a ternary complex mechanism.

PMID- 11229751
TI  - Synthesis and antitumor evaluation of novel monoindolyl-4
      trifluoromethylpyridines and bisindolyl-4-trifluoromethylpyridines.
AB  - A series of novel monoindolyl-4-trifluoromethylpyridines and bisindolyl-4
      trifluoromethylpyridines was designed and synthesized as potential antitumor
      agents. They were evaluated for preliminary cytotoxic activity against P388 and A
      549 cells with IC50 values. 4-Trifluoromethyl-2,6-bis[3'-(N-tosyl-6'-methoxyl
      indolyl)] pyridine was identified as the most potent in this series.

PMID- 11229752
TI  - Synthesis and biological activity of novel macrocyclic antifungals: acylated
      conjugates of the ornithine moiety of the lipopeptidolactone FR901469.
AB  - A series of acylated analogues of the novel macrocyclic lipopeptidolactone
      FR901469 has been prepared and evaluated for antifungal and hemolytic activity.
      Several analogues displayed markedly reduced hemolytic potential and comparable
      protective effects to the natural product in a mouse model of candidiasis.

PMID- 11229753
TI  - Evidence for gliotoxin-glutathione conjugate adducts.
AB  - The equilibrium constant for the gliotoxin/glutathione pair was found to be
      1200+/-100 M(-1) at pH 7.0 at 25 degrees C. Under conditions where the reaction
      was quenched rapidly with the addition of acid, gliotoxin-glutathione conjugate
      adducts were detected.

PMID- 11229755
TI  - Synthesis of substituted 4(Z)-(methoxyimino)pentyl-1-piperidines as dual NK1/NK2
      inhibitors.
AB  - The NK1 and NK2 receptor activity of a series of 5-[(3,5
      bis(trifluoromethyl)phenyl)methoxy]-3-(3,4-dichlorophenyl)-4(Z)
      (methoxyimino)pentyl-1-piperidines was evaluated. Compounds 11d, 11e, 11f, 12a,
      and 12k were found to be our most potent inhibitors.

PMID- 11229754
TI  - Synthesis and monoamine transporter affinity of 3beta-(4-(2-pyrrolyl)phenyl)-8
      azabicycl.
AB  - 3Beta-(5-indolyl)-8-azabicyclo[3.2.1]octanes display potent binding affinity for
      both the dopamine and serotonin transporters, while certain 3beta-(4-(2
      pyrrolyl)phenyl)-8-azabicyclo[3.2.1]octanes selectively bind to the serotonin
      transporter.

PMID- 11229756
TI  - Pharmacophore-based discovery, synthesis, and biological evaluation of 4-phenyl-1
      arylalkyl piperidines as dopamine transporter inhibitors.
AB  - Pharmacophore-based discovery, synthesis, and structure activity relationship
      (SAR) of a series of 4-phenyl-1-arylalkyl piperidines are disclosed. These
      compounds have been evaluated for their ability to inhibit reuptake of dopamine
      (DA) into striatal nerve endings (synaptosomes). The lead compound 5 and the most
      potent analogue 43 were found to have significant functional antagonism.

PMID- 11229757
TI  - Identification and characterization of a potential ischemia-selective N-methyl-D
      aspartate (NMDA) receptor ion-channel blocker, CNS 5788.
AB  - The identification and characterization of a potentially ischemia-selective and
      orally-active sulfoxide based NMDA ion-channel blocker showing good
      neuroprotective activity, (R)-(+)-N-(2-chloro-5-methylthiophenyl)-N'-(3
      methylsulfinylphenyl)-N'-methylguanidine (CNS 5788), is described.

PMID- 11229758
TI  - Targeting RNA with peptidomimetic oligomers in human cells.
AB  - Replication of human immunodeficiency virus type 1 (HIV-1) requires specific
      interactions of Tat protein with the transactivation responsive region (TAR) RNA,
      a 59-base stem-loop structure located at the 5'-end of all HIV mRNAs. Here we
      report that two TAR RNA-binding peptidomimetics, oligourea and oligocarbamate,
      inhibit transcriptional activation by Tat protein in human cells with an IC50 of
      approximately 0.5 and 1 microM, respectively. Peptidomimetics that can target
      specific RNA structures provide novel molecules that can be used to control
      cellular processes involving protein-RNA interactions in vivo.

PMID- 11229759
TI  - Initial structure-activity relationship of a novel class of nonpeptidyl GnRH
      receptor antagonists: 2-arylindoles.
AB  - A nonpeptidyl GnRH receptor antagonist (1), with a unique 2-arylindole core, was
      identified through the Merck in-house screening for binding affinity on the rat
      GnRH receptor. SAR studies directed toward the alkoxy-ethanolamine and 2-aryl
      groups resulted in a simpler lead structure with improved activity. This compound
      50 exhibits a 60-fold improvement in binding activity over our initial lead 1.

PMID- 11229760
TI  - SAR studies of novel 5-substituted 2-arylindoles as nonpeptidyl GnRH receptor
      antagonists.
AB  - The discovery of the potency-enhancing effect of 5-substitutions on the novel 2
      arylindoles as nonpeptidyl GnRH receptor antagonists led to the identification of
      several analogues with high affinities on the GnRH receptor. The syntheses and
      SARs of these 5-substituted-2-arylindole analogues are reported.

PMID- 11229762
TI  - Anti-HIV activity of aromatic and heterocyclic thiazolyl thiourea compounds.
AB  - Several thiazolyl thiourea derivatives were designed and synthesized as non
      nucleoside inhibitors (NNRTI) of HIV-1 reverse transcriptase. Six lead compounds
      were identified that showed subnanomolar IC50 values for the inhibition of HIV
      replication, were minimally toxic to human peripheral blood mononuclear cells
      (PBMC) with CC50 values ranging from 28 to >100 microM, and showed remarkably
      high selectivity indices ranging from 28,000 to >100,000. The most promising
      compound was N-[1-(1-furoylmethyl)]-N'-[2-(thiazolyl)]thiourea (compound 6),
      which showed potency against two NNRTI-resistant HIV-1 isolates (A17 and A17
      variant) at nanomolar to low micromolar concentrations, exhibited much greater
      potency against both wild-type as well as NNRTI-resistant HIV-1 than nevirapine,
      delavirdine, HI-443, and HI-244, was minimally toxic to PBMC, and had a
      selectivity index of > 100,000. The potency and minimal cytotoxicity of these
      aromatic/heterocyclic thiourea compounds suggest that they may be potentially
      useful as anti-AIDS drugs.

PMID- 11229763
TI  - Synthesis of analogues of the O-beta-D-ribofuranosyl nucleoside moiety of
      liposidomycins. Part 1: contribution of the amino group and the uracil moiety
      upon the inhibition of MraY.
AB  - The O-beta-D-ribofuranosyl nucleoside I is the minimal structural entity of
      liposidomycins maintaining enzyme inhibitory activity. Modifications performed on
      both the primary amine and the uracil moieties clearly demonstrate their major
      contribution to the inhibition of the bacterial translocase (MraY).

PMID- 11229761
TI  - 4,5,9,10-Tetrahydro-1,4-ethanobenz[b]quinolizine as a prodrug for its
      quinolizinium cation as a ligand to the open state of the TCP-binding site of
      NMDA receptors.
AB  - A new derivative of 4,5,9,10-tetrahydro-1,4-ethanobenz[b]quinolizine (2) has been
      designed as a prodrug for its quinolizinium cation (1) that is a potent
      antagonist of the TCP-binding site of NMDA receptors at the open state. The 11C
      labeled 2 showed high accumulation of radioactivity in the brain in an in vivo
      biodistribution study. The speculation of 2 as a prodrug of 1 has been proven by
      the fact that 1 was observed in a high ratio to 2 in an analysis by RP-HPLC of
      the brain homogenates.

PMID- 11229764
TI  - Synthesis of analogues of the O-beta-D-ribofuranosyl nucleoside moiety of
      liposidomycins. Part 2: role of the hydroxyl groups upon the inhibition of MraY.
AB  - O-beta-D-ribofuranosyl nucleoside I is the minimal structural entity of
      liposidomycins that maintains enzyme inhibitory activity on MraY. A set of
      compounds with hydroxyl patterns different from I has been synthesized. The
      presence of a hydroxyl group in the 3" position is essential for the activity.
      The 3'-deoxy derivative (IV), however, shows a 5-fold improved potency.

PMID- 11229765
TI  - Oxo-piperazine derivatives of N-arylpiperazinones as inhibitors of
      farnesyltransferase.
AB  - The evaluation of SAR associated with the insertion of carbonyl groups at various
      positions of N-arylpiperazinone farnesyltransferase inhibitors is described
      herein. 1-Aryl-2,3-diketopiperazine derivatives exhibited the best balance of
      potency and pharmacokinetic profile relative to the parent 1-aryl-2
      piperazinones.

PMID- 11229766
TI  - A series of quinoline analogues as potent inhibitors of C. albicans prolyl tRNA
      synthetase.
AB  - A series of quinoline inhibitors of C. albicans prolyl tRNA synthetase was
      identified. The most potent analogue, 2-(4-bromo-phenyl)-6-chloro-8-methyl-4
      quinolinecarboxylic acid, showed IC50 = 5 nM (Ca. ProRS) with high selectivity
      over the human enzyme.

PMID- 11229767
TI  - Structure-activity relationships of quinazoline derivatives: dual-acting
      compounds with inhibitory activities toward both TNF-alpha production and T cell
      proliferation.
AB  - We synthesized 4-chlorophenethylaminoquinazoline derivatives and evaluated their
      inhibitory activities toward both TNF-alpha production and T cell proliferation
      responses. Compound 2f, containing a piperazine ring at the C(7)-position of the
      quinazoline ring, exhibited more potent inhibitory activities toward both than
      the lead compound la. A smaller N-substituent in the piperazine ring was required
      for inhibition of TNF-alpha production.

PMID- 11229769
TI  - Semi-synthesis of 2-deoxo- and 3-epi-paraherquamide A.
AB  - 2-Deoxo- and 3-epi-paraherquamide A were synthesized from paraherquamide A. 2
      Deoxoparaherquamide A has good activity against HC and TC in our jird model
      comparable to the parent compound, while 3-epi-paraherquamide A showed no
      activity.

PMID- 11229768
TI  - Synthesis and structure-activity relationship of diarylamide derivatives as
      selective inhibitors of the proliferation of human coronary artery smooth muscle
      cells.
AB  - A series of diarylamide derivatives were synthesized and evaluated for their
      inhibitory activities against human coronary artery smooth muscle cells (SMCs)
      and human coronary artery endothelial cells (ECs). Compound 2w was superior to
      the lead compound, Tranilast, in terms of the potency of the activity and cell
      selectivity.

PMID- 11229770
TI  - Peptoids as endothelin receptor antagonists.
AB  - A series of new peptoids as endothelin receptor antagonists has been synthesized.
      Screening them for their ability to bind with endothelin receptors (ET(A) and
      ET(B)) competitively in the presence of (125I) endothelin led to the discovery of
      compounds as possible leads with IC50s in the low micromolar concentrations.

PMID- 11229771
TI  - Pimarane cyclooxygenase 2 (COX-2) inhibitor and its structure-activity
      relationship.
AB  - The structure-activity relationship and molecular modelings of a novel pimarane
      COX-2 inhibitor are reported. Particularly, a series of linker extended analogues
      designed on the basis of these studies exhibited significantly enhanced COX-2
      inhibitory activities and selectivities.

PMID- 11229772
TI  - Exploring the relationship between binding modes of 9-(aminomethyl)-9,10
      dihydroanthracene and cyproheptadine analogues at the 5-HT2A serotonin receptor.
AB  - Comparison of the serotonin 5-HT2A receptor affinities of a parallel series of
      structural analogues of the novel ligand 9-aminomethyl-9,10-dihydroanthracene
      (AMDA) and a structurally similar prototypical tricyclic amine cyproheptadine
      suggests that the two agents bind to the receptor in different fashions.
      Examination of ligand-receptor model complexes supports the experimental data and
      suggests a potential origin for the differences in binding modes.

PMID- 11229773
TI  - Selectivity of inhibition of matrix metalloproteases MMP-3 and MMP-2 by succinyl
      hydroxamates and their carboxylic acid analogues is dependent on P3' group
      chirality.
AB  - Structure-activity relationships are described for a series of succinyl
      hydroxamic acids 1a-o and their carboxylic acid analogues 2a-o as inhibitors of
      matrix metalloproteases MMP-3 and MMP-2. For this series (P1' = (CH2)3Ph, P2' = t
      Bu) selectivity for the inhibition of MMP-2 was found to be strongly dependent on
      P3'.

PMID- 11229774
TI  - Discovery of potent and selective succinyl hydroxamate inhibitors of matrix
      metalloprotease-3 (stromelysin-1).
AB  - Structure activity relationships are described for a series of succinyl
      hydroxamic acids 4a-o as potent and selective inhibitors of matrix
      metalloprotease-3 (stromelysin-1). Optimisation of P1' and P3' groups gave
      compound 4j (MMP-3 IC50=5.9nM) which was >140-fold less potent against MMP-1
      (IC50=51,000nM), MMP-2 (IC50=1790nM), MMP-9 (IC50=840nM) and MMP-14
      (IC50=1900nM).

PMID- 11229776
TI  - Development of novel telomerase inhibitors based on a bisindole unit.
AB  - Telomerase is the enzyme that elongates telomere repeat at the ends of a
      chromosome. As high telomerase activity is observed in most cancer cells,
      inhibitors of human telomerase have been expected as new chemotherapeutic agents
      for cancer. We describe here the discovery of novel inhibitors with IC50 values
      in the submicromolar range. The structure of the novel inhibitors will be useful
      as a scaffold for construction of the library in the search for telomerase
      inhibitors.

PMID- 11229775
TI  - Carbonic anhydrase inhibitors: synthesis of sulfonamides incorporating dtpa tails
      and of their zinc complexes with powerful topical antiglaucoma properties.
AB  - Reaction of diethylenetriamino pentaacetic acid (dtpa) dianhydride with
      aromatic/heterocyclic sulfonamides possessing a free
      amino/imino/hydrazino/hydroxy group afforded bis-sulfonamides containing metal
      complexing, polyamino-polycarboxylic acid moieties in their molecule. The
      corresponding mono-sulfonamide derivatives of dtpa were also obtained by an
      alternative method, from the free acid. Zn(II) complexes of these new
      sulfonamides were then prepared. Many of these derivatives showed nanomolar
      affinity towards isozymes I, II and IV of carbonic anhydrase (CA). Some of the
      best inhibitors were applied as 2% water solutions/suspensions into the eye of
      normotensive or glaucomatous albino rabbits, when strong and long-lasting
      intraocular pressure (IOP) lowering was observed.

PMID- 11229777
TI  - Pyrrolidine inhibitors of human cytosolic phospholipase A2. Part 2: synthesis of
      potent and crystallized 4-triphenylmethylthio derivative 'pyrrophenone'.
AB  - We synthesized a potent and crystallized human cytosolic phospholipase A2alpha
      inhibitor, pyrrophenone (6) which inhibits the isolated enzyme with an IC50 value
      of 4.2 nM. Pyrrophenone shows potent inhibition of arachidonic acid release,
      prostaglandin E2, thromboxane B2, and leukotriene B4 formation in human whole
      blood. The magnitudes of prostaglandin E2 and thromboxane B2 inhibition are the
      same as those of indomethacin.

PMID- 11229778
TI  - Aminoglycoside antibiotics, neamine and its derivatives as potent inhibitors for
      the RNA-protein interactions derived from HIV-1 activators.
AB  - Neamine derivatives which have an arginine (RN), a pyrene (PCN) and both pyrene
      and arginine (PRN) have been prepared and their binding toward the RNA fragments
      derived from HIV-1 activator region, TAR and RRE RNA were examined. Among them,
      PRN bound either TAR RNA or RRE RNA with equivalent binding affinities as Tat and
      Rev peptide, respectively.

PMID- 11229780
TI  - Synthesis and antiviral activity of novel D- and L-2'-azido-2',3'
      dideoxyribofuranosyl-4'-thiopyrimidines and purines.
AB  - Novel D- and L-2'-azido-2',3'-dideoxyribofuranosyl-4'-thiopyrimidines and purines
      have been synthesized starting from L-xylose and D-xylose, respectively. Among
      synthesized compounds tested against several viruses such as HIV-1, HSV-1, HSV-2,
      and HCMV, D-beta-N6-methyladenine (ent-22a) and D-alpha-N6-methyladenine (ent
      22b) analogues were found to exhibit significant anti-HCMV activity.

PMID- 11229779
TI  - New 5-HT1A receptor agonists possessing 1,4-benzoxazepine scaffold exhibit highly
      potent anti-ischemic effects.
AB  - A series of new 3-substituted-4-(4-aminobutyl)-1,4-benzoxazepin-5(4H)-one
      derivatives (1-5) which showed a very high affinity for 5-HT1A receptor with good
      selectivity over dopamine D2 receptor was synthesized. Among these compounds, 3
      chloro-4-[4-[4-(2-pyridinyl)-1,2,3,6-tetrahydropyridin-1-yl]butyl]-1,4
      benzoxazepin-5(4H)-one (5: SUN N4057) exhibited remarkable neuroprotective
      activity in a transient middle cerebral artery occlusion (t-MCAO) model.

PMID- 11229781
TI  - Controlled drug release: new water-soluble prodrugs of an HIV protease inhibitor.
AB  - We designed and synthesized a series of highly water-soluble prodrugs of an HIV
      protease inhibitor, KNI-727 (1), containing tandem-linked two auxiliary units, a
      solubilizing moiety and a self-cleavable spacer. Prodrugs with an ionized amino
      group at the solubilizing moiety exhibited a remarkable increase of water
      solubility (>10(4) fold) compared to the parent drug 1. These prodrugs released I
      not enzymatically, but chemically via an intramolecular cyclization-elimination
      reaction through an imide formation in physiological conditions. Diversified
      rates of parent drug release were observed when the chemical structure of both
      the solubilizing and the spacer moieties were modified. This new approach for
      water-soluble prodrugs will enable to control chemically the release of parent
      drug as well as to maintain high water-solubility.

PMID- 11229782
TI  - Measuring onset of antidepressant action in clinical trials: an overview of
      definitions and methodology.
AB  - This article discusses 4 critical questions that must be addressed in any valid
      analysis of comparative onset of therapeutic effect among antidepressant drugs:
      (1) how is onset defined, (2) how is onset measured, (3) how can the treatment
      groups be compared statistically with regard to onset of effect, and (4) how do
      these issues affect protocol design? A rigorous study of differential onset of
      effect should include an estimation of the portion of patients that respond, the
      timing of the onset of response, and the duration of response and an examination
      of the dynamic process of the onset of action. Methods for measuring symptom
      severity changes over time also will be reviewed.

PMID- 11229783
TI  - Evidence of early onset of antidepressant effect in randomized controlled trials.
AB  - Although antidepressant medications are effective in approximately 70% of
      patients with major depressive disorder, they have a delayed onset of therapeutic
      effect. This latency is problematic in that it prolongs the impairments
      associated with depression, leaves patients vulnerable to an increased risk of
      suicide, increases the likelihood that a patient will prematurely discontinue
      therapy, and increases medical costs associated with severe depression. No
      adequately designed prospective trials have been conducted to evaluate
      comparative time to onset of antidepressant effect. However, evidence suggests
      that some antidepressant agents may begin to work faster than others. Citalopram,
      venlafaxine, and mirtazapine each have exhibited statistically significant
      differences in some measures of antidepressant action within the first 2 weeks of
      treatment, both in placebo-controlled trials and in head-to-head comparisons with
      other antidepressants. This article reviews the data that hint at these drug
      specific differences in time to onset of action. Given the potential benefits of
      early-acting antidepressant treatments, the possibility of superior speed of
      onset of citalopram, venlafaxine, and mirtazapine presented here merits further
      study in adequately designed, prospective clinical trials.

PMID- 11229784
TI  - ECT and onset of action.
AB  - Although there is a long-standing clinical belief that electroconvulsive therapy
      (ECT) is the fastest available treatment for depression, ECT has not been
      compared directly with drug therapy. For this reason, it is impossible to say
      whether ECT treatment actually works faster than standard medications. Studies
      comparing various modalities of ECT have highlighted several factors that should
      be considered in any assessment of differential onset of antidepressant effect.
      First, patients are heterogeneous; that is, given any treatment or mode of
      treatment, some patients will respond, and some will not. Second, the choice of
      statistical method can significantly affect the interpretation of comparative
      onset data. Third, improved onset of action sometimes is achieved at the expense
      of tolerability. Thus, accelerating the onset of therapeutic response should not
      be an end in itself.

PMID- 11229786
TI  - Introduction: early onset of antidepressant action.

PMID- 11229785
TI  - Clinical significance of monitoring early symptom change to predict outcome.
AB  - Even with efforts to develop medication algorithms for the treatment of
      psychiatric illnesses, there is no single authoritative method that can be used
      to incorporate multiple factors in the treatment decision process. For this
      reason, physicians are faced with the often daunting task of sifting through the
      numerous treatment options for psychiatric illness to develop an approach that
      will prove the most successful for their patients. Investigating patient patterns
      of response, particularly during the acute phase of treatment, and bearing them
      in mind when developing treatment protocols may assist clinicians in optimally
      managing the degree and course of symptom response. We present here a
      consideration of the timing and nature of response as well as individual patient
      predictors, which may impact therapy decisions. Furthermore, we explore the
      clinical significance of integrating response patterns into the treatment
      approach. We believe that an analysis of response patterns, in conjunction with
      the use of other practice guidelines, is a viable method to more effectively
      navigate critical decision points in the treatment process and ultimately have a
      dramatic effect on patient outcome.

PMID- 11229787
TI  - An ideal trial to test differential onset of antidepressant effect.
AB  - Although various published clinical studies have suggested that some
      antidepressants may have a more rapid onset of therapeutic effect than others,
      none of these trials was adequately designed to measure differential time to
      onset of effect. Thus, existing data do not support claims that one drug reduces
      the symptoms of depression faster than another. In this article, we propose a
      study that would be ideal for measuring comparative onset of antidepressant
      effect. The key features of this ideal trial include (1) a prospective definition
      of early onset of action, (2) increased frequency of assessment, (3) a data
      analytic approach capable of capturing the dynamic nature of symptomatic change,
      and (4) various strategies to minimize bias and heterogeneity of response.

PMID- 11229788
TI  - Early onset of antidepressant action: impact on primary care.
AB  - Although the prevalence of depression among patients in primary care is high, the
      primary care system is inefficient at recognizing and managing this disorder. The
      delayed onset of antidepressant effect contributes to this problem, since
      patients and physicians may prematurely discontinue a medication that is not
      perceived as effective. The undertreatment of depression has profound effects on
      patients, the health care system, and society. The development of antidepressants
      with a faster onset of action would improve the pharmacologic management of
      depression and have wide-ranging benefits for the health care system.

PMID- 11229789
TI  - Possible neurobiological mechanisms underlying faster onset of antidepressant
      action.
AB  - All antidepressant drugs have a delayed onset of action. There is, however,
      evidence that some agents may attenuate depressive symptoms more rapidly than
      others. The present review examines the mechanisms by which selective serotonin
      reuptake inhibitors, the dual 5-HT norepinephrine reuptake inhibitor venlafaxine,
      and the alpha2-adrenoceptor antagonist mirtazapine alter 5-HT and/or
      norepinephrine neurotransmission. Particular attention is given to the time
      course with which these effects manifest themselves in relation to the
      possibility that these 3 types of drugs may act more rapidly, or exert a greater
      antidepressant action, than other agents. Based on the effects of antidepressant
      drugs presently available, strategies to accelerate or augment the antidepressant
      response are described, some of which have already been examined in patients.

PMID- 11229790
TI  - Withered Yang: a review of traditional Chinese medical treatment of male
      infertility and erectile dysfunction.

PMID- 11229791
TI  - Potential application of gene therapy for the treatment of erectile dysfunction.

PMID- 11229792
TI  - Making lives to save lives.

PMID- 11229793
TI  - Sperm morphology assessment--historical perspectives and current opinions.

PMID- 11229794
TI  - Testicular secretion of inhibin in the male golden hamster (Mesocricetus
      auratus).
AB  - To identify the cellular source of inhibin in the male golden hamster, we have
      used complementary approaches, immunohistochemistry and enzyme-linked
      immunosorbent assay (ELISA). Strong positive staining of the inhibin alpha
      subunit was observed in both the Sertoli and Leydig cells of the testes. No
      specific staining was observed for the inhibin betaA subunit, whereas specific
      staining for the inhibin betaB subunit was strongly positive in the Leydig cells.
      Inhibin pro-alphaC and inhibin B were detected in peripheral plasma, and
      testicular homogenate also contained large amounts of inhibin pro-alphaC and
      inhibin B. However, inhibin A was not detected either in peripheral plasma or in
      testicular homogenate. Plasma concentrations of inhibin pro-alphaC and inhibin B
      were significantly (P < .001) decreased 24 hours after orchidectomy. These
      results strongly suggest that the Leydig cells are the main source of dimeric
      inhibin B in the male golden hamster.

PMID- 11229795
TI  - Epididymal growth and differentiation are altered in human cryptorchidism.
AB  - Despite the knowledge and histological classification of testicular lesions,
      epididymal lesions associated with cryptorchidism are not well defined and only
      macroscopic alterations have been reported. We have evaluated the alterations in
      the growth of both the epithelium and muscular wall of efferent ducts and
      epididymis in human patients with cryptorchidism from infancy to adulthood. In
      addition, by cytokeratin immunostaining we have also evaluated the stage of
      differentiation of each segment along the human postnatal life in these patients.
      A decrease is shown in the size of efferent and epididymal ducts in cryptorchid
      children compared with normal, age-matched controls. The height of the
      epithelium, muscular wall, and lumen of the cryptorchid epididymis were reduced
      at every age studied. This decrease in all regions was seen even in the
      testicular quiescent period (1 to 4 years of age). In addition, the cryptorchid
      epididymis grows more slowly during the transition to the pubertal period. The
      smaller size of the cryptorchid epididymis in pubertal and adult men compared
      with that of normal men is due primarily to underdevelopment of the muscular wall
      and a reduction in epithelial height. The pattern of growth of cryptorchid
      efferent ducts and ductus epididymides parallels that in normal men, except that
      development of the lumen and muscular layer in the cauda epididymis region are
      delayed. Epithelial differentiation, monitored by cytokeratin expression, is
      minimal in efferent ducts and throughout the epididymis of the cryptorchid male,
      and this is already seen in children. In conclusion, our immunohistochemical and
      morphometric results show a reduced development of the human cryptorchid
      epididymis that is already evident in childhood. They indicate that
      cryptorchidism is a primary congenital illness of the testis and spermatic ducts,
      with evident lesions from the first years of life, and suggest that surgical
      descent would probably not be able to completely reverse these alterations.

PMID- 11229796
TI  - Marked species specificity of guinea pig luteinizing hormone: validation of a
      bioassay.
AB  - The Guinea pig is a potentially interesting alternative small animal model for
      the study of the neuroendocrine regulation of reproduction. However, appropriate
      gonadotropin assays are not widely available for this species. The aim of the
      present study was to validate a bioassay procedure for guinea pig luteinizing
      hormone (LH). The well-established interstitial cell-testosterone in vitro
      bioassays with the use of dispersed mouse or rat Leydig cells, successfully
      applied for measurement of LH from a variety of mammalian species, were found to
      be unsuitable for assay of guinea pig LH because of a marked species specificity
      of guinea pig LH. An alternative bioassay procedure was established with the use
      of dispersed guinea pig Leydig cells. This assay has been shown to allow for the
      assessment of serum LH response to exogenous gonadotropin-releasing hormone and
      of the expected spontaneous pulsatile pattern of basal LH secretion, with an
      apparent mean serum LH pulse interval of 31.4 minutes and 51.9 minutes, in long
      term castrated and sham operated male guinea pigs, respectively. This bioassay
      can be a useful tool for more intensive exploration of guinea pig reproductive
      physiology.

PMID- 11229797
TI  - Sperm structural and motility changes during aging in the Brown Norway rat.
AB  - The Brown Norway rat provides a useful model to study aging of the male
      reproductive tract because of the selective age-dependent pathological changes
      that are found in the testis, epididymis, and prostate. In the testis, there is a
      clear age-dependent decrease in both steroidogenesis and spermatogenesis. In the
      epididymis, some striking segment-specific changes occur at the histological and
      biochemical levels prior to the major loss of spermatogenesis. We hypothesized
      that formation of spermatozoa in the testis and maturation of spermatozoa in the
      epididymis (ie, acquisition of motility and loss of the cytoplasmic droplet) may
      be altered during aging. Changes in the morphology of spermatozoa were assessed
      by light and electron microscopy. Using computer-assisted sperm analysis, the
      motility parameters of spermatozoa obtained from the caput and cauda epididymidis
      of young and old Brown Norway rats were compared. In old animals, we also
      compared the motility of spermatozoa from epididymides adjacent to regressed
      testes with those from epididymides adjacent to nonregressed testes. There was a
      marked increase with age in the number of spermatozoa with abnormal flagellar
      midpieces; the nature of these defects did not change with age. In caput
      epididymidis, the percentage of motile sperm was similar in young and old rats.
      In contrast, the percentage of motile spermatozoa was significantly decreased in
      cauda epididymidis of old rats; spermatozoa from the regressed testis side had
      altered motility characteristics. Furthermore, in the cauda epididymidis on the
      regressed testis side of aged Brown Norway rats, the proportion of spermatozoa
      that retained their cytoplasmic droplet was markedly elevated. Some of these
      effects are likely due to changes taking place in spermatozoa during the process
      of spermatogenesis in the testis (eg, formation of the flagellum), whereas others
      could occur during sperm maturation in the epididymis (eg, acquisition of
      motility). The multiple effects of aging on sperm morphology, the acquisition of
      motility, and the shedding of the cytoplasmic droplet clearly indicate that the
      quality of spermatozoa is affected by aging.

PMID- 11229798
TI  - Melatonin inhibits the expression of steroidogenic acute regulatory protein and
      steroidogenesis in MA-10 cells.
AB  - The effects of melatonin on steroidogenesis and steroidogenic acute regulatory
      (StAR) protein expression were investigated in MA-10 mouse Leydig tumor cells. MA
      10 cells were treated with human chorionic gonadotropin/cyclic adenosine
      monophosphate (hCG/cAMP) analogue alone or with hCG/cAMP analogue plus melatonin
      in different dosages (0.1 nM to 10 microM). Steroid production and the expression
      of StAR protein were measured. Melatonin directly inhibited hCG- or dbcAMP
      stimulated progesterone production in MA-10 cells within 3 hours. The inhibitory
      effects of melatonin on hCG- or dbcAMP-stimulated steroid production in MA-10
      cells were abolished by a comparative melatonin receptor antagonist, luzindole.
      22R-hydroxycholesterol reversed melatonin's inhibitory effects, which illustrated
      that melatonin did not suppress P450scc enzyme activity. Moreover, StAR protein
      expression stimulated by hCG and dbcAMP was maximally reduced by 10 nM of
      melatonin treatment for 3 hours. The effects of prolonged exposure (12 h) to
      melatonin with dbcAMP stimulation in MA-10 cells were also examined. The
      expression of StAR protein and steroid production were reduced by melatonin
      concentrations from 1 nM to 10 microM. However, melatonin at a dose of 1 nM had
      no effect in 3-hour treatment. Our results indicate that melatonin suppressed MA
      10 mouse Leydig cell steroidogenesis through specific binding sites by blocking
      StAR protein expression without altering the activity of P450scc enzyme.

PMID- 11229800
TI  - In vitro fertilization with intracytoplasmic sperm injection is an effective
      therapy for male factor infertility related to subnormal hypo-osmotic swelling
      test scores.
AB  - The aim of the study was to determine if intracytoplasmic sperm injection (ICSI)
      would be an effective therapy for mates with subnormal hypo-osmotic swelling test
      (HOST) scores, a condition known to prevent implantation of embryos despite
      allowing normal fertilization and embryo formation. Couples in whom the male
      partner had a HOST score of <50% and failed to achieve a pregnancy despite at
      least 3 cycles of intrauterine insemination with chymotrypsin-galactose-treated
      sperm were treated with in vitro fertilization (IVF) with ICSI. The clinical and
      viable pregnancy rates were 49.0% and 45.3% (n = 53). The implantation rate was
      27.1%. These data thus demonstrate that ICSI is an effective therapy for
      infertile couples in whom the male partner has a subnormal hypo-osmotic swelling
      (HOS) score. Previous studies using conventional IVF without ICSI when HOS was
      subnormal found normal fertilization rates but a marked reduction in pregnancy
      and implantation rates. The very acceptable pregnancy and implantation rates
      demonstrated in this study with ICSI is consistent with the hypothesis that the
      defect associated with sperm that have subnormal HOST scores is not related to
      the single spermatozoon that is responsible for fertilizing the oocyte but may be
      related to a toxic factor associated with the supernumerary sperm attached to the
      zona pellucida.

PMID- 11229799
TI  - The effect of cardiac arrest on the blood-testis barrier to albumin, tumor
      necrosis factor-alpha, pituitary adenylate cyclase activating polypeptide,
      sucrose, and verapamil in the mouse.
AB  - Impotence commonly occurs after events such as acute myocardial infarction,
      coronary bypass, head trauma, and cerebral bleeding, including subarachnoid
      hemorrhage. We hypothesize that the hypoxia accompanying these events could
      damage the blood-testis barrier (BTB) and so cause testicular dysfunction, a
      possible cause of impotence. We examined the effect of cardiac arrest in mice on
      testis weight and various aspects of BTB function. Testis weight was decreased by
      about 24% 12 hours after cardiac arrest but had recovered fully by day 7. The
      testis/serum ratio for albumin was increased 12 hours after arrest, showing a
      disruption in the vascular BTB with recovery by 24 hours. The testis/serum ratio
      for sucrose was not consistently elevated, showing that the Sertoli cell BTB
      remained intact. The testis/serum ratio for verapamil was increased on day 3 of
      cardiac arrest, suggesting impaired function of the BTB's p-glycoprotein efflux
      transporter. Transporters for pituitary adenylate cyclase activating polypeptide
      and tumor necrosis factor-alpha were not affected by cardiac arrest. These
      results show that cardiac arrest affects testis weight and some aspects of BTB
      function. Such changes might have long-term effects on testicular function.

PMID- 11229801
TI  - Regulation of Sertoli cell myotubularin (rMTM) expression by germ cells in vitro.
AB  - Recent studies have shown that rat myotubularin (rMTM), the homolog of human
      myotubularin, which is a putative protein tyrosine phosphatase (PTP), is
      expressed by Sertoli cells in the rat testis. In addition, a significant increase
      in its steady-state mRNA level was detected in Sertoli cells at the time of inter
      Sertoli tight junction (TJ) assembly in vitro. Since the interplay of protein
      kinases and phosphatases that determines the intracellular phosphoprotein content
      can, in turn, regulate the assembly and maintenance of TJ and anchoring junctions
      (AJ) in vitro, as demonstrated in different cell types, such as Madin-Darby
      canine kidney (MDCK) cells, endothelial cells, and Sertoli cells, rMTM may be an
      important molecule in regulating the assembly and maintenance of inter-Sertoli
      TJs during spermatogenesis. We thus sought to characterize its regulation. During
      testicular maturation, it was shown that the rMTM steady-state mRNA level
      increased drastically with aging. The expression of rMTM increased by as much as
      2-4-fold in the rat testis at 45-60 days of age versus 20 days of age, coinciding
      with the onset of spermiation. This result seemingly suggests that rMTM may
      participate in the release of spermatids by disassembling the Sertoli-spermatid
      AJs, since PTP inhibitor was shown to perturb the inter-Sertoli TJ permeability
      barrier in vitro. Unexpectedly, when Sertoli cells were isolated from 20-, 45-,
      and 90-day-old rats and the steady-state rMTM level was quantified, it was shown
      that there is a drastic reduction in rMTM expression in adult Sertoli cells.
      Studies that used Sertoli-germ cell cocultures and Sertoli cells incubated with
      increasing germ cell-derived proteins have shown that the high level of
      testicular rMTM expression in the testis might be maintained by germ cells.
      Although work remains to be done to delineate the role of rMTM in the testis,
      these results illustrate that germ cells play a very active role in regulation
      testicular function by altering the phosphoprotein content.

PMID- 11229802
TI  - Changes in motion characteristics, plasma membrane integrity, and acrosome
      morphology during cryopreservation of buffalo spermatozoa.
AB  - Motion characteristics, plasma membrane integrity, and acrosome morphology of
      buffalo spermatozoa after different stages of cryopreservation (ie, dilution,
      cooling to 4 degrees C, equilibration at 4 degrees C, and freezing and thawing)
      were examined. Semen ejaculates from 4 buffalo bulls were pooled (n = 5), diluted
      in tris-citric acid extender, cooled to 4 degrees C over 2 hours, equilibrated at
      4 degrees C for 4 hours, dispensed into 0.5-mL straws, and frozen in a
      programmable cell freezer before plunging into liquid nitrogen. Frozen semen was
      thawed at 37 degrees C for 15 seconds. After completion of each stage, sperm
      motion characteristics, plasma membrane integrity, and acrosomal morphology were
      determined using computer-assisted semen analysis, hypo-osmotic swelling assay,
      and phase-contrast microscopy, respectively. Data were presented as mean +/-
      standard error of the mean. Visual and computerized motility did not differ due
      to dilution, cooling, or equilibration (77.3% +/- 2.3% and 90.5% +/- 1.2%,
      respectively), but was reduced (P < .05) after freezing and thawing (53.0% +/-
      4.6% and 48.6% +/- 6.5%, respectively). Linear motility of spermatozoa was lower
      (P < .05) after dilution or equilibration (56.2% +/- 2.4%) than after cooling or
      freezing and thawing (79.6% +/- 1.4%). Sperm curvilinear velocity was reduced (P
      < .05) from 112.4 +/- 5.3 microm/sec after dilution to 96.0 +/- 5.8 microm/s
      after cooling, and from 87.6 +/- 4.1 microm/s after equilibration to 69.4 +/- 2.0
      microm/s after freezing and thawing. Sperm lateral head displacement differed (P
      < .05) after each stage (ie, dilution, 3.9 +/- 0.2 microm; cooling, 2.3 +/- 0.2
      microm; equilibration, 3.1 +/- 0.3 microm; and freezing and thawing, 1.7 +/- 0.2
      microm). Spermatozoa with intact plasma membranes were 80.2% +/- 3.9% after
      dilution, reduced (P < .05) to 60.4% +/- 5.6% after equilibration, and then to
      32.6% +/- 3.8% after freezing and thawing. The percentage of spermatozoa with
      normal acrosomes remained higher after dilution, cooling, or equilibration (73.2%
      +/- 2.4%) than after freezing and thawing (61.8% +/- 2.4%; P < .05). In
      conclusion, the maximal damage to the motility apparatus, plasma membrane, and
      acrosomal cap of buffalo spermatozoa occurs during freezing and thawing followed
      by equilibration.

PMID- 11229803
TI  - Thyroid hormone receptors in neonatal, prepubertal, and adult rat testis.
AB  - Thyroid hormone (TH) is involved in the differentiation and development of rat
      testis, whereas its role in adult testis function is still undefined. The aim of
      our work has been to further analyze the presence in the testis of rats of
      various ages of messenger RNA (mRNA) coding the different TH receptor (TR)
      subtypes using a sensitive assay, such as reverse transcriptase-polymerase chain
      reaction (RT-PCR). To rule out the possibility of an "illegitimate
      transcription," we have analyzed both T3-binding capacity of adult rat testis and
      the presence in the same organ of TR proteins by immunohistochemistry, using
      specific antibodies directed against the various TR isoforms. Messenger RNA
      coding for TR alpha1 and alpha2 isoforms was clearly visible in gels prepared
      from RT-PCR samples obtained from the testis of rats of all ages, including
      adults, whereas mRNA for the TR beta1-beta2 was absent. The T3 maximal binding
      capacity (Cmax) by nuclear extracts of testicular homogenates gradually decreased
      from birth to adulthood, still remaining significantly detectable in adult
      testis, and represented approximately 1% of the Cmax observed in the liver. The
      immunostaining technique revealed an intense nuclear staining along the basement
      membrane of testicular tubules prepared from rats of all ages and incubated with
      an antipeptide antibody specific for TR alpha1 (alpha1-403). Staining with an
      antipeptide antibody specific for TR beta1 (beta-62) was never present. Our data
      show that mRNAs coding for the functional TR alpha1, and also for the still
      undefined alpha2, are present in the testis of rats of all ages. T3-binding
      activity and immunohistochemical studies confirmed that the message is translated
      into proteins. The transcriptional activity clearly decreased from birth to
      adulthood, but it still remained significantly present. The presence of a TR
      alpha1 message indicates that the adult rat testis may be directly responsive to
      T3 and, therefore, suggests an action of TH on rat testis that is not only
      developmental, but also metabolic.

PMID- 11229804
TI  - Ecto-ATPase mRNA is regulated by FSH in Sertoli cells.
AB  - A putative messenger RNA (mRNA) sequence, designated C8, that was up-regulated in
      Sertoli cells prepared from hypophysectomized rats treated with testosterone, was
      isolated from a Sertoli cell complementary DNA (cDNA) library. The coding region
      of C8 exhibited 99% identity with rat brain ecto-ATPase and expressed a 60
      kilodalton protein following in vitro transcription/translation. Transfection of
      COS7 cells with C8 cDNA resulted in a marked increase in Ca2+- and Mg2+-dependent
      ATPase activity in both whole cells and cell homogenates, which is consistent
      with localization of this enzyme in the plasma membrane. C8 ecto-ATPase steady
      state mRNA levels were increased within 6 hours and for 3 day, by follicle
      stimulating hormone (FSH) in Sertoli cells but not in peritubular cells. In
      contrast, dibutyryl-cyclic adenosine monophosphate (cAMP) increased ecto-ATPase
      in both Sertoli and peritubular cells. Testosterone had no significant effect
      under these conditions. These data indicate that ecto-ATPase mRNA is positively
      regulated by FSH in Sertoli cells and by cAMP in both Sertoli and peritubular
      cells. This enzyme may play a role in the control of extracellular signaling by
      ATP, adenosine, or both in the cells of the seminiferous epithelium.

PMID- 11229805
TI  - Molecular genetic analysis of two human sperm fibrous sheath proteins, AKAP4 and
      AKAP3, in men with dysplasia of the fibrous sheath.
AB  - Dysplasia of the fibrous sheath (DFS) is characterized by male infertility,
      asthenozoospermia, and morphologically abnormal flagella that possess a severely
      malformed fibrous sheath. In many cases, DFS is familial, suggesting a genetic
      component. Human AKAP4 and AKAP3 are structural proteins of the fibrous sheath
      that also function to anchor protein kinase A to this structure via the
      regulatory subunit of the kinase. We hypothesized that defects in either AKAP4 or
      AKAP3 might cause DFS. No quantitative or qualitative differences between
      patients with DFS and normal controls were detected when sperm proteins were
      analyzed by either silver staining or immunoblot analysis using antibodies raised
      against AKAP4 and AKAP3. Additionally, AKAP4 and AKAP3 from DFS sperm retained
      the ability to bind the regulatory subunit of protein kinase A. Localization at
      the light and electron microscopic levels showed that AKAP3 and AKAP4 localized
      correctly to the FS of the amorphous flagellum in DFS sperm. Partial sequence
      analysis of the AKAP4 and AKAP3 genes in patients with DFS did not identify any
      significant alterations in potential AKAP4/AKAP3 binding regions, suggesting that
      the two proteins interact normally in DFS sperm. Our results did not find
      evidence to support the hypothesis that mutations in either gene are responsible
      for DFS in humans.

PMID- 11229806
TI  - Oxidative stress in normospermic men undergoing infertility evaluation.
AB  - The purpose of this study was to determine whether normospermic infertile men
      have high seminal oxidative stress, using 3 measures of oxidative stress:
      reactive oxygen species (ROS), total antioxidant capacity (TAC), and a composite
      ROS-TAC score. Forty-three normospermic men without leukocytospermia and 19
      healthy donors who came to our infertility clinic were included. Patients were
      categorized into 3 groups: group I, varicocele and no female factor (n = 16);
      group II, positive female factor (n = 16); and group III, idiopathic infertility
      (n = 11). In addition, 52 treated male factor patients and 19 donors were
      included as reference groups. We measured seminal ROS, TAC, and the ROS-TAC score
      in the patient groups and the controls. Normospermic infertile patients as a
      group had higher ROS levels (mean log [ROS + 1] 1.76 +/- 0.13) compared with
      controls (1.39 +/- 0.16; P = .03). Patients in the idiopathic subgroup had
      significantly higher ROS levels (2.29 +/- 0.25; P = .004) than controls.
      Normospermic infertile patients as a group not only had reduced TAC levels
      (970.18 +/- 73.95 Trolox equivalents), but each subgroup also had significantly
      lower TAC than controls (1650.93 +/- 95.87; P < .003). The ROS-TAC scores in all
      normospermic infertile patients as a group (35.7 +/- 1.8) as well as in each
      subgroup was significantly reduced compared with the ROS-TAC levels in the
      controls (50.0 +/- 2.1; P < .005). We conclude that oxidative stress is
      associated with male factor infertility. The presence of oxidative stress in
      infertile normospermic men may explain previously unexplained cases of
      infertility otherwise attributed to female factors.

PMID- 11229807
TI  - Suppression of androgen action and the induction of gross abnormalities of the
      reproductive tract in male rats treated neonatally with diethylstilbestrol.
AB  - This study evaluated whether androgen action is altered in rats treated
      neonatally with diethylstilbestrol (DES) at a dose that induced reproductive
      tract abnormalities. Rats were treated on alternate days 2-12 with 10 microg DES
      and studied on Day 18. DES-induced abnormalities included a 70% reduction in
      testis weight, distension and overgrowth of the rete, distension and reduction in
      epithelial height of the efferent ducts, underdevelopment of the epididymal duct
      epithelium, reduction in epithelial height in the vas deferens, and convolution
      of the extra-epididymal vas. In DES-treated rats, androgen receptor (AR)
      immunoexpression was virtually absent from all affected tissues and the testis,
      whereas AR expression in controls was intense in epithelial and stromal cells.
      The DES-induced change in AR immunoexpression was confirmed by Western analysis
      for the testis. In rats treated neonatally with 1 microg DES, reproductive
      abnormalities were absent or minor, except for a 38% reduction in testis weight;
      loss of AR immunoexpression also did not occur in these rats. Treatment-induced
      changes in AR expression were paralleled by changes in Leydig cell volume per
      testis (91% reduction in the 10-microg DES group; no change in the 1-microg DES
      group). To test whether suppression of androgen production or action alone could
      induce comparable reproductive abnormalities to 10 microg DES, rats were treated
      neonatally with either a potent gonadotropin-releasing hormone antagonist (GnRHa)
      or with flutamide (50 mg/kg/day). These treatments reduced testis weight (68% for
      GnRHa, 40% for flutamide), and generally retarded development of the reproductive
      tract but failed to induce the abnormalities induced by 10 microg DES. GnRHa and
      flutamide caused no detectable change in AR immunoexpression in target tissues,
      with the exception of minor changes in the testes of flutamide-treated males.
      GnRHa treatment caused a reduction (83%) in Leydig cell volume comparable to that
      caused by 10 microg DES. Immunoexpression of estrogen receptor alpha (ER alpha)
      in the efferent ducts and of ER beta in all tissues studied were unaffected by
      any of the above treatments. Neonatal coadministration of testosterone esters
      (TE; 200 microg) with 10 microg DES prevented most of the morphological
      abnormalities induced by 10 microg DES treatment alone, though testis weight was
      still subnormal (46% reduction in DES + TE vs 72% in DES alone and 49% with TE
      alone) and some lumenal distension was still evident in the efferent ducts.
      Coadministration of TE with DES prevented DES-induced loss of AR immunoexpression
      (confirmed for testis by Western blot analysis). It is concluded that 1)
      reproductive tract abnormalities induced in the neonatal male rat by a high (10
      microg) dose of DES are associated with reduced AR expression and Leydig cell
      volume; 2) these changes are largely absent with a lower dose of DES (1 microg);
      3) treatments that interfere with androgen production (GnRHa) or action
      (flutamide) alone failed to induce reproductive tract abnormalities or alter AR
      expression as did 10 microg DES; 4) a grossly altered androgen:estrogen balance
      (low androgen + high estrogen) may underlie the reproductive tract abnormalities,
      other than reduced testis weight, induced by high doses of DES.

PMID- 11229809
TI  - DNA and conducting electrons.

PMID- 11229808
TI  - Dialysis addition of trehalose/glycerol cryoprotectant allows recovery of
      cryopreserved mouse spermatozoa with satisfactory fertilizing ability as assessed
      by yield of live young.
AB  - Mouse sperm cryopreservation provides a means for storing the genetic information
      in genetically modified mice (mutants, transgenics, and "knockouts") in a cost-
      and space-effective manner. Sperm from this species are highly sensitive to
      cryodamage, which has impeded their cryopreservation in the past. The
      cryoprotectant used in this study was 6% glycerol (0.65 M) plus 7.5% trehalose
      (0.22 M), which was added to a concentrated suspension of sperm from B6SJLF1/J
      mice in bicarbonate-free buffer by dialysis to minimize osmotic stress on the
      cells. Sperm suspensions were frozen in 0.25 mL straws and stored in liquid N2.
      Eggs were obtained from B6SJLF1/J superovulated females. For in vitro
      fertilization (IVF), 15-25 microL of sperm suspension post-thaw from one straw
      was added directly to each of three 1.5 mL drops of fertilization medium
      containing 30 eggs each, for 3 replicates per experiment. The fertilized eggs
      were scored for blastocyst formation, after which 12 blastocysts from each drop
      were implanted into pseudopregnant CD-1 females. The number of live pups were
      then scored at birth. Ten experiments yielded 21.7 +/- 1.4 (SD) blastocysts per
      30 eggs inseminated (72%) and 7.3 +/- 0.4 (SD) live pups per 12 blastocysts
      implanted (61%). The overall yield of live pups was 44 per 100 eggs inseminated
      (44%). This yield should be satisfactory for maintaining a mouse strain through
      sperm cryostorage, with restart of the strain through IVF and embryo transfer.
      The method should also provide improvement in human sperm cryopreservation, as
      human sperm are less sensitive to cryodamage than are mouse sperm.

PMID- 11229810
TI  - Signal regulation by family conspiracy.
AB  - The signal regulating proteins (SIRPs) are a family of ubiquitously expressed
      transmembrane glycoproteins composed of two subgroups: SIRP alpha and SIRP beta,
      containing more than ten members. SIRP alpha has been shown to inhibit signalling
      through a variety of receptors including receptor tyrosine kinases and cytokine
      receptors. This function involves protein tyrosine kinases and is dependent on
      immunoreceptor tyrosine-based inhibition motifs which recruit key protein
      tyrosine phosphatases to the membrane. Negative regulation by SIRP alpha may also
      involve its ligand, CD47, in a bi-directional signalling mechanism. The SIRP beta
      subtype has no cytoplasmic domain but instead associates with at least one other
      transmembrane protein (DAP-12, or KARAP). DAP-12 possesses immunoreceptor
      tyrosine-based activation motifs within its cytoplasmic domain that are thought
      to link SIRP beta to activating machinery. SIRP alpha and SIRP beta thus have
      complementary roles in signal regulation and may conspire to tune the response to
      a stimulus.

PMID- 11229811
TI  - Genes in sweeping competition.
AB  - Analysis of DNA variation is a powerful tool for detecting adaptation at the
      genomic level. The contribution of adaptive evolution is evident from examples of
      rapidly evolving genes, which represent the likely targets for strong selection.
      More subtle adaptation is also an integral component of routine maintenance of
      gene performance, continuously applied to every gene. Adaptive changes in the
      population are accomplished through selective sweeps, i.e. complete or partial
      fixation of beneficial alleles. The evidence is accumulating that selective
      sweeps are quite frequent events which, together with associated genetic
      hitchhiking, represent dominant forces that influence molecular evolution by
      shaping the variability pattern in the genome.

PMID- 11229812
TI  - T-antigen regulated expression reduces apoptosis of tag-transformed human
      myoblasts.
AB  - The generation of human myogenic cell lines could potentially provide a valuable
      source for cell transplantation in myopathies. The dysregulation of proliferative
      differentiative signals by viral oncogenes can result in the induction of
      apoptosis. Whether apoptosis occurred in myogenic cells expressing large T
      antigen (Tag) from SV40 upon differentiation was unknown. Human muscle satellite
      cells were transfected with two different constructs, containing either an origin
      defective SV40 genome or Tag under vimentin promoter control. When
      differentiation was triggered, Tag expression reduced the formation of myotubes
      and dead cells showing apoptotic features were present. However, the cells
      expressing SV40 Tag under vimentin promoter control retained their capacity to
      form myotubes and expressed the myofibrillar proteins as myosin heavy chain and
      dystrophin when Tag expression was silent. Their apoptotic rate was similar to
      that of untransfected cells. The observation that apoptosis can be prevented by
      the down-regulation of Tag suggests that the programmed cell death induced in
      transformed cells can be reversed, and confirms the regulatory efficiency of the
      human vimentin promoter.

PMID- 11229813
TI  - Sialyl Lewis(x)-liposomes as vehicles for site-directed, E-selectin-mediated drug
      transfer into activated endothelial cells.
AB  - E-selectin, exclusively expressed on activated endothelial cells, is a potential
      target for site-directed delivery of agents. We and others have shown that sialyl
      LewisX-liposomes (sLe(x)-liposomes) are recognized by E-selectin. We now report
      an approach employing sLe(x)-liposomes to deliver antisense oligonucleotides (AS
      ODNs) directed against the adhesion molecule ICAM-1 to activated vascular
      endothelial cells. ICAM-1 expression was analyzed at the protein level by
      immunofluorescence and a cell surface ELISA, and at the RNA level by RT-PCR. We
      have investigated two different AS-ODNs complementary to the 3' untranslated
      region and the AUG translation initiation codon of ICAM-1 mRNA. Both inhibited
      protein expression, but did not influence the mRNA level, pointing to a
      hybridization of AS-ODNs with the mRNA in the cytoplasm. Our results demonstrate
      the feasibility of a novel approach for the delivery of agents to activated
      endothelial cells by glycoliposomes targeted to E-selectin.

PMID- 11229814
TI  - Porcine factor V: cDNA cloning, gene mapping, three-dimensional protein modeling
      of membrane binding sites and comparative anatomy of domains.
AB  - Factor V is a plasma protein essential for blood coagulation. This protein is
      involved in activated protein C resistance, the most common inherited thrombotic
      disorder known. We utilized the polymerase chain reaction to clone the porcine
      factor V gene by generating overlapping clones amplified with primers chosen by
      comparison with known nucleotide sequences. The porcine factor V cDNA contig
      encodes a predicted 2258-amino acid protein, making it the largest in comparison
      to the bovine, human, and murine proteins. Porcine factor V has the highest level
      of homology with bovine factor V, but also has high levels of conservation of
      important residues with all the species. Radiation hybrid mapping assigned the
      porcine factor V gene to chromosome 4. Three-dimensional models of factor V were
      generated and used to analyze membrane-binding sites in terms of conserved, and
      therefore likely important residues.

PMID- 11229815
TI  - The CD40/CD154 receptor/ligand dyad.
AB  - Until recently, the expression and primary function of the cell surface receptor
      CD40 and its ligand CD154 were considered restricted to B and T lymphocytes, and
      their interactions required for the thymus-dependent humoral response. However,
      current work from several groups challenges this view of the CD40/CD154 dyad as a
      mere mediator of lymphocyte communication. A variety of non-lymphocytic cell
      types express both receptor and ligand, including hematopoetic and non
      hematopoetic cells, such as monocytes, basophils, eosinophils, dendritic cells,
      fibroblasts, smooth muscle, and endothelial cells. Accordingly, ligation of CD40
      mediates a broad variety of immune and inflammatory responses, such as the
      expression of adhesion molecules, cytokines, matrix-degrading enzymes,
      prothrombotic activities, and apoptotic mediators. Consequently, CD40 signaling
      has been associated with pathogenic processes of chronic inflammatory diseases,
      such as autoimmune diseases, neurodegenerative disorders, graft-versus-host
      disease, cancer, and atherosclerosis. This review focuses on the synthesis and
      structure of CD40 and outlines CD154/CD40 signaling pathways, and emphasizes the
      previously unexpected importance of the CD40/CD154 receptor/ligand dyad in a
      spectrum of immunoregulatory processes and prevalent human diseases.

PMID- 11229816
TI  - Origin of organic molecules and biomolecular homochirality.
AB  - Theories about the origin of biomolecular homochirality, which seems to be a
      prerequisite for the creation of life, are discussed. First, possible terrestrial
      and extraterrestrial sources of organic molecules are outlined. Then, mechanisms
      for the formation of enantiomerically enriched compounds and for the
      amplification of their chirality are described.

PMID- 11229818
TI  - Protein folds: molecular systematics in three dimensions.
AB  - Advances in methods of structure determination have led to the accumulation of
      large amounts of protein structural data. Some 500 distinct protein folds have
      now been characterized, representing one-third of all globular folds that exist.
      The range of known structural types and the relatively large fraction of the
      protein universe that has already been sampled have greatly facilitated the
      discovery of some unifying principles governing protein structure and
      evolutionary relationships. These include a highly skewed distribution of
      topological arrangements of secondary-structure elements that favors a few very
      common connectivities and a highly skewed distribution in the capacity of folds
      to accommodate unrelated sequences. These and other observations suggest that the
      number of folds is far fewer than the number of genes, and that the fold universe
      is dominated by a small number of giant attractors that accommodate large numbers
      of unrelated sequences. Thus all basic protein folds will likely be determined in
      the near future, laying the foundation for a comprehensive understanding of the
      biochemical and cellular functions of whole organisms.

PMID- 11229817
TI  - Ammonia and amino acid transport across symbiotic membranes in nitrogen-fixing
      legume nodules.
AB  - Biological nitrogen fixation involves the reduction of atmospheric N2 to ammonia
      by the bacterial enzyme nitrogenase. In legume-rhizobium symbioses, the
      nitrogenase-producing bacteria (bacteroids) are contained in the infected cells
      of root nodules within which they are enclosed by a plant membrane to form a
      structure known as the symbiosome. The plant provides reduced carbon to the
      bacteroids in exchange for fixed nitrogen, which is exported to the rest of the
      plant. This exchange is controlled by plant-synthesised transport proteins on the
      symbiosome membranes. This review summarises our current understanding of these
      transport processes, focusing on ammonia and amino acid transport.

PMID- 11229819
TI  - Regulation of G1 phase progression by growth factors and the extracellular
      matrix.
AB  - Cell cycle progression is regulated by both intracellular and extracellular
      control mechanisms. Intracellular controls ensure that cell cycle progression is
      stopped in response to irregularities such as DNA damage or faulty spindle
      assembly, whereas extracellular factors may determine cell fate such as
      differentiation, proliferation or programmed cell death (apoptosis). When
      extracellular factors bind to receptors at the outside of the cell, signal
      transduction cascades are activated inside the cell that eventually lead to
      cellular responses. We have shown previously that MAP kinase (MAPK), one of the
      proteins involved in several signal transduction processes, is phosphorylated
      early after mitosis and translocates to the nucleus around the restriction point.
      The activation of MAPK is independent of cell attachment, but does require the
      presence of growth factors. Moreover, it appears that in Chinese hamster ovary
      cells, a transformed cell line, growth factors must be present early in the G1
      phase for a nuclear translocation of MAPK and subsequent DNA replication to
      occur. When growth factors are withdrawn from the medium immediately after
      mitosis, MAPK is not phosphorylated, cell cycle progression is stopped and cells
      appear to enter a quiescent state, which may lead to apoptosis. Furthermore, in
      addition to this growth-factor-regulated decision point in early G1 phase,
      another growth-factor-sensitive period can be distinguished at the end of the G1
      phase. This period is suggested to correlate with the classical restriction point
      (R) and may be related to cell differentiation.

PMID- 11229820
TI  - The presynaptic cytomatrix of brain synapses.
AB  - Synapses are principal sites for communication between neurons via chemical
      messengers called neurotransmitters. Neurotransmitters are released from
      presynaptic nerve terminals at the active zone, a restricted area of the cell
      membrane situated exactly opposite to the postsynaptic neurotransmitter reception
      apparatus. At the active zone neurotransmitter-containing synaptic vesicles (SVs)
      dock, fuse, release their content and are recycled in a strictly regulated
      manner. The cytoskeletal matrix at the active zone (CAZ) is thought to play an
      essential role in the organization of this SV cycle. Several multi-domain
      cytoskeleton-associated proteins, including RIM, Bassoon, Piccolo/Aczonin and
      Munc-13, have been identified, which are specifically localized at the active
      zone and thus are putative molecular components of the CAZ. This review will
      summarize our present knowledge about the structure and function of these CAZ
      specific proteins. Moreover, we will review our present view of how the
      exocytotic and endocytic machineries at the site of neurotransmitter release are
      linked to and organized by the presynaptic cytoskeleton. Finally, we will
      summarize recent progress that has been made in understanding how active zones
      are assembled during nervous system development.

PMID- 11229821
TI  - Elevated levels of free tissue factor pathway inhibitor antigen in cases of
      disseminated intravascular coagulation caused by various underlying diseases.
AB  - Tissue factor pathway inhibitor (TFPI) is primarily synthesized by vascular
      endothelial cells and is found in vivo in association with endothelial cells,
      lipoproteins, or in free form. Free TFPI is the most potent and important type,
      because it is released from endothelial cells following an injection of heparin,
      or as a result of pathological stimuli. In order to study the role of TFPI in
      disease, the concentration of free form TFPI was measured in the plasma of 114
      patients suffering from disseminated intravascular coagulation (DIC), as the
      result of several underlying diseases. Plasma antigen levels of free TFPI were
      significantly higher even in those patients not exhibiting DIC than in normal
      healthy subjects. These levels were even higher among patients exhibiting DIC,
      especially those with acute promyelocytic leukemia or cancer, receiving
      continuous heparin drip infusions. A significant correlation was observed between
      the plasma antigen levels of free form TFPI and those of fibrin/fibrinogen
      degradation products, and free form TFPI and plasmin inhibitor complex (r =
      0.428, P < 0.0001 and r = 0.329, P < 0.0001, respectively) among 114 DIC
      patients. There were no significant differences between the plasma levels of free
      TFPI in DIC patients with or without multiple organ failure. It has been
      suggested that the plasma levels of free TFPI are closely related to the levels
      of fibrinolysis occurring in DIC patients, although further study is required to
      clarify the degree to which TFPI is expressed by endothelial cells during DIC.

PMID- 11229822
TI  - Hemostatic and fibrinolytic parameters in survivors of myocardial infarction: a
      low plasma level of plasmin-alpha2-antiplasmin complex is an independent
      predictor of coronary re-events.
AB  - Abnormalities of coagulation or fibrinolysis play a role in the pathogenesis of
      coronary artery disease (CAD). Elevated plasma levels of fibrinogen, von
      Willebrand factor antigen, plasminogen activator inhibitor-1 and tissue-type
      plasminogen activator were reported to be predictive for reinfarction and death
      in patients with CAD. We investigated the risk for coronary re-events associated
      with 18 hemostatic and fibrinolytic parameters in a prospective study including
      200 survivors of myocardial infarction (MI). During a 2-year follow-up, 37
      patients suffered one of the following predefined re-events: fatal MI (n = 2),
      non-fatal MI (n = 5), percutaneous transluminal coronary angioplasty (n = 17) or
      coronary artery bypass grafting (n = 13). Low plasmin-alpha2-antiplasmin complex
      (PAP) plasma levels were associated with an up to fivefold (95% confidence
      interval, 1.6-15.3) increase in relative risk. The association between decreasing
      PAP levels and coronary re-events remained significant (P = 0.004) after
      correction for possible confounders using multiple logistic regression analysis.
      Our data indicate low PAP plasma levels to be associated with subsequent coronary
      events in patients with a history of MI.

PMID- 11229823
TI  - Hemostatic effects of antithrombin III supplementation during cardiac surgery:
      results of a prospective randomized investigation.
AB  - Failure to suppress thrombin generation during cardiac surgery promotes fibrin
      generation, fibrinolysis, and a consumptive coagulopathy. Acquired deficiencies
      of antithrombin III may play a contributory role. We hypothesized that
      antithrombin III supplementation to normal physiologic concentrations would
      decrease thrombin generation and potentially reduce peri-operative bleeding.
      Twenty patients undergoing coronary artery bypass graft surgery were randomized
      for this prospective, double-blind, placebo-controlled study. Ten patients
      received antithrombin III supplementation (50 U/kg) by intravenous infusion prior
      to incision, and 10 patients received a placebo. Blood samples were obtained pre
      operatively, at 1 and 2 h following initiation of cardiopulmonary bypass (CPB),
      and at 1, 3, and 24 h after completion of CPB. Samples were analyzed for
      antithrombin III, thrombin-antithrombin III (TAT) complex, and D-dimer
      concentrations. Cumulative blood loss was recorded at 6 and 12 h after CPB. No
      statistically significant differences in patient demographics or total heparin
      dose administered were observed between groups. As expected, plasma antithrombin
      III concentrations were maintained near pre-operative values in the treatment
      group, but not in the placebo group. Despite this difference, no statistically
      significant alterations in generation of TAT complex, D-dimer, or blood loss
      occurred between groups. Antithrombin III supplementation to maintain normal
      physiologic concentrations during CPB did not alter significantly thrombin
      generation, fibrinolytic activity, or blood loss in adults undergoing elective
      cardiac surgery.

PMID- 11229824
TI  - A rapid and cost-effective method for analysis of three common genetic risk
      factors for thrombosis.
AB  - A simple, rapid and cost-effective method for the analysis of three of the most
      widely screened genetic risk factors for thrombosis has been established. The
      protocol developed uses blood spots stored on filter paper (Guthrie spots) as
      well as DNA extracted from anticoagulated blood. The use of Guthrie spots taken
      at birth enables the retrospective study of patients who develop thrombotic
      complications without necessitating resampling. Following isolation of DNA,
      conventional fluorescence-labelled polymerase chain reaction (PCR) is performed
      using a thermostable DNA polymerase. Denatured, single-stranded PCR products are
      analysed on a semi-automated capillary-based genetic analyser, the data being
      stored electronically. This sensitive protocol obviates the need for endonuclease
      digestion and the associated gel running and documentation, and leads to a
      reduction in the recurrent costs of laboratory consumables.

PMID- 11229825
TI  - Determination of plasma aprotinin levels by functional and immunologic assays.
AB  - We compared a functional (amidolytic) and an enzyme-linked immunosorbent assay
      (ELISA) method for determining aprotinin concentration in 82 plasma samples
      obtained from patients undergoing cardiac surgery with aprotinin therapy. There
      was good correlation between methods (r = 0.87); however, aprotinin measurements
      by chromogenic assay were significantly higher than by ELISA [234 +/- 104
      kallikrein inhibitory units (KIU)/ml versus 155 +/- 88 KIU/ml; P = 0.0001]. This
      appeared to be attributable to differences in the potency of the material used to
      standardize the assays. When results were corrected to allow for potency of the
      standard, there was no significant difference between chromogenic and ELISA
      methods (234 +/- 104 KIU/ml versus 240 +/- 137 KIU/ ml), although the ELISA
      results tended to be higher in some samples. These data suggest that aprotinin
      concentrations measured by these methods cannot be used interchangeably, and care
      must be taken when interpreting data from studies measuring aprotinin.

PMID- 11229826
TI  - Increased soluble P-selectin in patients with haematological and breast cancer: a
      comparison with fibrinogen, plasminogen activator inhibitor and von Willebrand
      factor.
AB  - Abnormal platelet activation and an increased risk of thrombosis are frequent
      findings in cancer. As soluble adhesion molecule P-selectin is being increasingly
      recognized as reflecting increased platelet activation, we hypothesized raised
      levels in patients with cancer, obtaining plasma from 24 patients with a cross
      section of haematological cancers, 41 with breast cancer, and from an equal
      number of healthy controls for each patient group. Levels of soluble P-selectin
      were compared with those of von Willebrand factor (vWf), plasminogen activator
      inhibitor-1 (PAI-1) activity and fibrinogen (markers of endothelial integrity,
      fibrinolysis and coagulation, respectively). We found raised soluble P-selectin,
      fibrinogen and vWf in both patient groups compared with their controls (P <
      0.01). vWf and soluble P-selectin were higher in the haematological cancers than
      in breast cancer patients (by 30 and 74%, respectively; both P < 0.01). There was
      no significant difference in levels of PAI-1 between any group. There were no
      differences in soluble P-selectin or vWf when the data from the women with breast
      cancer were classified according to tumour size, lymph node involvement or
      presence of vascular invasion. We conclude that the platelet marker soluble P
      selectin is raised in both haematological and breast cancer, and is higher in the
      former, but is unrelated to the type or stage of breast cancer.

PMID- 11229827
TI  - Impact of the fibrinolytic enzyme system on prognosis and survival associated
      with non-small cell lung carcinoma.
AB  - Comprehensive studies of fibrinolysis in non-small cell lung carcinoma have been
      limited, and assignment of patients to high/low prognosis groups based on
      arbitrary cut-offs utilizing fibrinolytic measurements is unstandardized. This
      study was performed in 166 patients to examine the effects of cut-off values
      determined in three ways. Model 1 assigned patients to one of three equal groups
      (low, medium, high) based on fibrinolytic measurements made at diagnosis, Model 2
      divided patients into low/high groups using median values, and Model 3 grouped
      according to the parameter being above/below normal range. In model 1, raised
      plasma fibrinogen, D-dimer and soluble fibrin were positively associated with
      poorer survival. In model 2, tissue plasminogen activator antigen was
      additionally related to poorer prognosis. Model 3 identified seven parameters as
      significantly related to survival, two not identified by the other models
      becoming significant [plasmin-antiplasmin, tissue plasminogen activator inhibitor
      1 (PAI-1) antigen]. Using multivariate analysis, plasma fibrinogen level was the
      most uniformly significant parameter. Relative risk estimates indicated that
      raised plasma fibrinogen, soluble fibrin and D-dimer were associated with
      increased risk of death. Use of the normal/above normal cut-off is recommended to
      provide the maximum number of significant parameters relating to prognosis, and
      increased plasma D-dimer, PAI-1 antigen and fibrinogen were most closely related
      to survival/prognosis.

PMID- 11229828
TI  - Increased plasma fibrinolysis and tissue-type plasminogen activator/tissue-type
      plasminogen activator inhibitor ratios after ethanol withdrawal in chronic
      alcoholics.
AB  - The effects of alcohol withdrawal on fibrinolysis were studied in 10 middle-aged
      male chronic alcoholics institutionalized for withdrawal therapy. All patients
      were sampled on admission [day 1 (D1)] and 21 days after alcohol withdrawal [day
      22 (D22)]. The overall plasma fibrinolytic capacity (OFC) was assayed by
      measuring the ability of patient plasma to generate D-dimers from a standardized
      fibrin clot, and tissue-type plasminogen activator (t-PA) and t-PA inhibitor (PAI
      1) levels were assayed together with serum cholesterol, triglyceride and
      cholesterol fractions. At D22, the OFC significantly increased in seven patients
      [D1 = 10 +/- 0.7 microg/h (mean +/- SD), D22 = 17 +/- 7.4 microg/h; P < 0.01],
      while t-PA and PAI-1 levels decreased in all patients but two (t-PA: D1 = 16.6 +/
      5 ng/ml, D22 = 10.2 +/- 3.8 ng/ml; P < 0.001; and PAI-1: D1 = 46 +/- 39 ng/ml,
      D22 = 21 +/- 28 ng/ml; P < 0.01). This study clearly demonstrates an increase in
      overall fibrinolytic activity after alcohol withdrawal, which is mainly due to a
      decrease in PAI-1 levels. These changes induced by alcohol abstinence might
      provide clear benefit by reducing the risk of thromboembolic events and
      particularly of stroke associated with elevated PAI-1 levels described in heavy
      drinkers.

PMID- 11229829
TI  - A randomized trial of the effects of garlic oil upon coronary heart disease risk
      factors in trained male runners.
AB  - Most trials of bulb garlic and garlic powder tablets indicate reduced coronary
      heart disease (CHD) risk in elevated-risk subjects. Most persons taking garlic
      supplements lack overt risk of CHD. However, no trials have tested steam
      distilled garlic oil (GO) capsules with healthy subjects. The objectives of the
      present randomized, double-blind, placebo-controlled study were to determine
      whether GO capsules reduce CHD risk in trained male runners. Twenty-seven
      volunteers (mean age, 28.8 years) completed the study. Each took 12.3 mg/day GO
      (or placebo) capsules for 16 weeks. Main outcome measures were 95% confidence
      intervals (CIs) between GO and placebo groups for differences in changes of blood
      pressure (BP), plasma lipids, total antioxidant status (TAS), low-density
      lipoprotein (LDL) composition and blood clotting factors. Principal results as
      mean differences (95% CI) between GO and placebo are: pulse, 2.9 beats/min (-0.8
      to 6.7), P = 0.12; systolic BP, -4.5 mmHg (-10.8 to 1.9), P = 0.16; plasma total
      cholesterol, 0.01 mmol/l (-0.34 to 0.37), P = 0.95; plasma triglycerides, -0.20
      mmol/l (-0.43 to 0.03), P = 0.09; plasma TAS, 45 micromol Trolox equivalent/l (
      35 to 124), P = 0.26; LDL density, 0.0019 g/ml (-0.0005 to 0.0043), P = 0.12; LDL
      triglycerides/protein, -0.078 mg/mg (-0.149 to -0.007), P = 0.03; LDL
      cholesterol/protein, -0.24 mg/mg (-0.69 to 0.22), P = 0.3; LDL TAS/triglycerides,
      29 nmol/mg (11, 68), P = 0.15; prothrombin time, 0.99 s (-0.36 to 2.35), P =
      0.14; partial thromboplastin time, 3.0 s (-1.0 to 7.1), P = 0.13. Results were
      null statistically. Trends with GO were mostly towards lower CHD risk, and a
      larger study (approximately 150 subjects) is required to test their validity.

PMID- 11229830
TI  - The inhibition of TNK-t-PA by C1-inhibitor.
AB  - TNK-t-PA is a recombinant mutant of tissue plasminogen activator that has a
      longer half-life and higher selectivity for fibrin than normal tissue plasminogen
      activator (t-PA). In addition, it is reported to be serpin resistant because of
      reduced inhibition by plasminogen activator inhibitor-1. In this study, we have
      investigated the inhibition of TNK-t-PA by the serpin C1-inhibitor. TNK-t-PA is
      inhibited with a second-order rate constant of 7.5 per mol/l per s compared with
      4.5 per mol/l per s for t-PA. In both cases, the stoichiometry was close to 20,
      indicating that C1-inhibitor was predominantly a substrate for both forms of t
      PA. The formation of cleaved C1-inhibitor was seen on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE), and the t-PA-C1-inhibitor (or TNK
      t-PA-C1-inhibitor) complex seen on SDS-PAGE and by zymography. Although the rates
      of inhibition are very slow in vitro, the fact that in vivo formation of the t-PA
      C1-inhibitor complex after infusion of t-PA has been well documented suggests
      that TNK-t-PA will also be inhibited by C1-inhibitor in vivo and, perhaps more
      importantly, could cause a significant reduction in C1-inhibitor concentration.

PMID- 11229831
TI  - Unsuspected hyperhomocysteinemia in chronically anticoagulated patients.
AB  - Hyperhomocysteinemia is a risk factor for arterial and venous thrombosis. The aim
      of this study was to evaluate plasmatic homocysteine levels in patients under
      chronic anticoagulant treatment with dietary restriction of green vegetables.
      This kind of food is a very important source not only of vitamin K but also of
      folates, which are involved in Hcy metabolism. It is known that the lower the
      folate levels, the higher the Hcy concentration, so we suspected that these
      patients could show hyperhomocysteinemia. A group of patients receiving oral
      anticoagulant treatment and a restricted diet (Group I, n = 20) was compared with
      a group of untreated subjects of a similar age that were not on a restricted diet
      (Group II, n = 35). Group I showed significantly higher levels of plasmatic Hcy
      and significantly lower levels of serum folate than Group II. Therefore, a diet
      restricted in vitamin K applied to oral anticoagulated patients could induce an
      unwanted increase of homocysteine levels.

PMID- 11229832
TI  - . . . relationship between dislipidemia and thrombosis yet unproven.

PMID- 11229833
TI  - Reversal of excessive oral anticoagulation with a low oral dose of vitamin K1
      compared with acenocoumarine discontinuation. A prospective, randomized, open
      study.
AB  - We performed a prospective, randomized, open study in 109 outpatients under
      chronic anticoagulation with acenocoumarine, presenting with International
      Normalized Ratios (INRs) > or = 6.0 and no or minor bleeding. All the patients
      withheld one dose of acenocoumarine; in addition, a treated group also received 1
      mg oral vitamin K1. We aimed at a post-intervention INR < 6.0, with a target zone
      of 2.0-4.0. The INRs were lowered from a mean of 8.1 +/- 1.7 to 4.9 +/- 2.5 in
      the controls (P = 0.0000) and from 8.4 +/- 2.4 to 3.3 +/- 3 in the treated
      patients (P = 0.0000). There were no differences in the percentage of patients
      with post-intervention INRs < 6.0 or within the therapeutic zone. One-third of
      the treated patients and only 2% of the controls reached INRs < 2.0 (P = 0.0003).
      Oral vitamin K1 offered no advantage to the simple discontinuation of one dose of
      acenocoumarine. A substantial number of treated patients were consequently
      exposed to under-anticoagulation.

PMID- 11229834
TI  - Infectious diseases: considerations for the 21st century.
AB  - The discipline of infectious diseases will assume added prominence in the 21st
      century in both developed and developing nations. To an unprecedented extent,
      issues related to infectious diseases in the context of global health are on the
      agendas of world leaders, health policymakers, and philanthropies. This attention
      has focused both on scientific challenges such as vaccine development and on the
      deleterious effects of infectious diseases on economic development and political
      stability. Interest in global health has led to increasing levels of financial
      support, which, combined with recent technological advances, provide
      extraordinary opportunities for infectious disease research in the 21st century.
      The sequencing of human and microbial genomes and advances in functional genomics
      will underpin significant progress in many areas, including understanding human
      predisposition and susceptibility to disease, microbial pathogenesis, and the
      development new diagnostics, vaccines, and therapies. Increasingly, infectious
      disease research will be linked to the development of the medical infrastructure
      and training needed in developing countries to translate scientific advances into
      operational reality.

PMID- 11229835
TI  - Mortality and costs of acute renal failure associated with amphotericin B
      therapy.
AB  - To assess the mortality and resource utilization that results from acute renal
      failure associated with amphotericin B therapy, 707 adult admissions in which
      parenteral amphotericin B therapy was given were studied at a tertiary-care
      hospital. Main outcome measures were mortality, length of stay, and costs; we
      controlled for potential confounders, including age, sex, insurance status,
      baseline creatinine level, length of stay before beginning amphotericin B
      therapy, and severity of illness. Among 707 admissions, there were 212 episodes
      (30%) of acute renal failure. When renal failure developed, the mortality rate
      was much higher: 54% versus 16% (adjusted odds of death, 6.6). When acute renal
      failure occurred, the mean adjusted increase in length of stay was 8.2 days, and
      the adjusted total cost was $29,823. Although residual confounding exists despite
      adjustment, the increases in resource utilization that we found are large and the
      associated mortality is high when acute renal failure occurs following
      amphotericin B therapy.

PMID- 11229836
TI  - Outbreak of adenovirus genome type 7d2 infection in a pediatric chronic-care
      facility and tertiary-care hospital.
AB  - An outbreak of adenovirus infection that involved residents of a pediatric
      chronic-care facility, staff of a tertiary-care hospital, and a nosocomial
      hospital case was studied. In the pediatric facility, 31 (33%) of 93 residents
      had adenovirus infection, and 8 died. Risk factors for illness were an age of < 7
      years (P = .004), presence of a tracheostomy (P = .015), and residence on a
      particular floor (P < .001). In the tertiary-care hospital, 36 health care
      workers had adenovirus infection; 26 (72%) had failed to follow strict contact
      and droplet precautions, and 30 (83%) continued to care for patients while they
      had symptoms. A 5-month-old patient with underlying lung disease acquired severe
      adenovirus infection in this hospital. All isolates were adenovirus type 7 (Ad7).
      DNA restriction analysis revealed the band patterns of all isolates to be
      identical and characteristic of the genome type d2. Thus, Ad7d2 caused
      significant morbidity and mortality in persons in the pediatric chronic-care
      facility and tertiary-care hospital. This is the first published description of
      Ad7d2 strains in the United States.

PMID- 11229837
TI  - Risk factors for acquisition of levofloxacin-resistant Streptococcus pneumoniae:
      a case-control study.
AB  - A case-control study was conducted to identify the risk factors associated with
      levofloxacin-resistant Streptococcus pneumoniae (LRSP) colonization or infection.
      Twenty-seven case patients (patients with LRSP) were compared with 54 controls
      (patients with levofloxacin-susceptible S. pneumoniae). Risk factors that were
      significantly associated with LRSP colonization or infection, according to
      univariate analysis, included an older age (median age, 75 years for case
      patients versus 72.5 years for controls), residence in a nursing home (odds ratio
      [OR], 7.2), history of recent (OR, 4.6) and multiple (OR, 4.4) hospitalizations,
      prior exposure to fluoroquinolones (OR, 10.6) and beta-lactams (OR, 8.6),
      presence of chronic obstructive pulmonary disease (COPD; OR, 5.9), and nosocomial
      origin of the bacteria (OR, 5.7). Multivariate analysis showed that presence of
      COPD (OR, 10.3), nosocomial origin of the bacteria (OR, 16.2), residence in a
      nursing home (OR, 7.4), and exposure to fluoroquinolones (OR, 10.7) were
      independently associated with LRSP colonization or infection. Thus, a distinct
      group of patients with COPD is the reservoir of LRSP.

PMID- 11229838
TI  - Risk factors for severe pulmonary and disseminated coccidioidomycosis: Kern
      County, California, 1995-1996.
AB  - Surveillance for coccidioidomycosis (CM) and a case-control study for risk
      factors among adults were conducted in Kern County, California. From January 1995
      through December 1996, 905 cases of CM were identified, for an annual incidence
      of 86 cases per 100,000 population. A total of 380 adults were enrolled in the
      case-control study: 77 had severe pulmonary disease, 33 had disseminated disease,
      and 270 control patients had mild disease. Independent risk factors for severe
      pulmonary disease included diabetes, recent history of cigarette smoking, income
      of < $15,000 per year, and older age. Oral antifungal therapy before
      hospitalization was associated with a reduced risk of CM pneumonia. Risk factors
      for disseminated disease were black race, income of < $15,000 per year, and
      pregnancy. Early treatment of CM with oral antifungal agents may prevent severe
      pulmonary disease in groups considered to be at high risk, such as elderly
      individuals, persons with diabetes, and smokers. Persons at risk for severe CM
      may benefit from vaccination once an effective CM vaccine is available.

PMID- 11229839
TI  - Reappraisal of lung tap: review of an old method for better etiologic diagnosis
      of childhood pneumonia.
AB  - Identification of the etiology of childhood pneumonia is difficult, even in the
      cases that most likely have bacterial origins. A positive blood culture result is
      diagnostic but rare (< 10% of cases), and other noninvasive microbiological
      methods are nonspecific or are at least shadowed by interpretation problems.
      However, lung tap (or aspiration), a method developed a century ago, warrants
      reappraisal, especially since the prevalence of pneumococcal resistance to
      penicillin is increasing. An analysis of 59 studies that were published in 6
      languages led us to conclude that (1) bacterial etiology is disclosed in
      approximately 50% of cases (virological tests were rarely done); (2) lung tap is
      safer than is generally considered; (3) potential pneumothorax is mostly
      symptomless and resolves spontaneously without impairing recovery; and (4) in
      comparison with routine diagnostic tools, lung tap offers so many advantages that
      it warrants reconsideration at centers where personnel have experience in
      handling potential pneumothorax.

PMID- 11229840
TI  - Do guidelines for community-acquired pneumonia improve the cost-effectiveness of
      hospital care?
AB  - There is growing pressure to demonstrate the value of practice guidelines. We
      have reviewed the evidence that guidelines for the treatment of community
      acquired pneumonia (CAP) change current practices and that the standardization of
      practices reduces costs and/or improves outcome. The most obvious barrier to
      implementation of the guidelines is lack of knowledge about their content;
      equally important are the attitudes and behavior of professionals, patients, and
      their caregivers. Guidelines may improve the outcome of CAP, provided that there
      is an association between variations in outcome and some specific processes of
      care. Conversely, when there is no such relationship, guidelines may reduce the
      cost of care without having an adverse effect on outcome. The cost-effectiveness
      of CAP guidelines in an individual hospital depends on the systems that are
      available to identify patients with CAP and to measure the processes of care.
      There is good evidence that following the recommendations of the CAP guidelines
      does improve the cost-effectiveness of care and, therefore, that an audit of CAP
      may be worth the effort.

PMID- 11229842
TI  - Uninspiring aspiring fellows (UNAFs): an emerging infectious disease.

PMID- 11229841
TI  - Preemptive therapy versus universal prophylaxis with ganciclovir for
      cytomegalovirus in solid organ transplant recipients.
AB  - Whether preemptive therapy or universal prophylaxis with ganciclovir is the
      optimal approach against cytomegalovirus (CMV) remains unresolved. Controversy
      abounds with respect to the efficacy of preemptive therapy, the reliability of
      preemptive therapy tools, the logistical difficulties in conducting surveillance
      monitoring for CMV, the cost of prophylaxis, the effect of prophylaxis on
      indirect sequelae of CMV and epidemiology of CMV, and the potential for emergence
      of ganciclovir-resistant CMV. Although neither approach is wholly adequate, a
      discussion of the relative merits and limitations of the 2 approaches may guide
      the selection of a rational approach toward prevention of CMV infection in organ
      transplant recipients.

PMID- 11229843
TI  - Counterpoint: UNAFs--perspective and prevention.

PMID- 11229844
TI  - Internet and computer-based resources for travel medicine practitioners.
AB  - The field of travel medicine is concerned primarily with ways to maintain the
      health of international travelers. Remaining current in this area requires up-to
      date knowledge of global infectious diseases, patterns of drug resistance,
      advances in preventive measures, and public health regulations pertaining to the
      crossing of international borders. This review of off-line commercial databases
      and Internet sources will assist infectious disease consultants in accessing
      current reliable travel health information. Of the North American pretravel off
      line databases, TRAVAX (United States) and The Medical Letter are the most
      comprehensive, whereas the Global Infectious Disease and Epidemiology Network is
      extraordinary in its provision of global infectious disease epidemiology for
      posttravel assessment. A total of 65 Web sites are listed within 9 categories,
      covering such areas as authoritative government travel health recommendations,
      commercially-oriented sites, and travel medicine listserv discussion groups. Even
      among reputable Web sites, contradictory information may be found that demands
      careful consideration by the clinician and by the traveling public.

PMID- 11229846
TI  - Clinical use of genotypic and phenotypic drug resistance testing to monitor
      antiretroviral chemotherapy.
AB  - Assays that detect antiretroviral drug resistance in human immunodeficiency virus
      have recently become available to clinicians. Phenotypic assays measure the drug
      susceptibility of the virus by determining the concentration of drug that
      inhibits viral replication in tissue culture. Genotypic assays determine the
      presence of mutations that are known to confer decreased drug susceptibility.
      Although each type of assay has specific advantages, limitations associated with
      these tests often complicate the interpretation of results. Several retrospective
      clinical trials have suggested that resistance testing may be useful in the
      assessment of the success of salvage antiretroviral therapy. Prospective,
      controlled trials have demonstrated that resistance testing improves short-term
      virological response. Resistance testing is currently recommended to help guide
      the choice of new drugs for patients after treatment has failed and for pregnant
      women. Resistance testing should also be considered for treatment-naive patients,
      to detect transmission of resistant virus.

PMID- 11229845
TI  - Use of cytokines in human immunodeficiency virus-infected patients: colony
      stimulating factors, erythropoietin, and interleukin-2.
AB  - The recombinant human cytokines granulocyte colony-stimulating factor (G-CSF),
      granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin, and
      interleukin-2 (IL-2) have been manufactured and licensed. Studies have been
      carried out that investigate the use of G-CSF and GM-CSF to reverse leukopenia,
      as adjunctive therapy for HIV-associated infections and for novel approaches to
      treat HIV infection, including stem cell mobilization. In addition, studies that
      identified the role of erythropoietin in the management of anemia have been
      performed. Furthermore, the abilities of G-CSF and erythropoietin to permit the
      continued use of marrow suppressive agents that are key in managing HIV infection
      have been assessed. The aim of this review is to summarize these studies and to
      describe the reports that evaluate the use of IL-2 to enhance elevation of CD4
      cell counts mediated by highly active antiretroviral therapy. This summary is
      important to the treating clinician in that it identifies the optimal use of
      these cytokines in current clinical practice as well as their potential future
      roles.

PMID- 11229847
TI  - Preevaluation of clinical trial data: the case of preemptive cytomegalovirus
      therapy in patients with human immunodeficiency virus.
AB  - We developed a mathematical simulation model to anticipate outcomes from an
      upcoming trial of targeted, preemptive cytomegalovirus (CMV) therapy in high
      risk, human immunodeficiency virus (HIV)-infected patients identified by means of
      CMV polymerase chain reaction screening. We estimated the costs and consequences
      of CMV prophylaxis in patients with CD4(+) counts < or =100 cells/microL under
      various assumptions regarding disease progression, complication rates, drug
      effects, and costs. Without CMV preemptive therapy, lifetime costs average
      $44,600 with expected duration of survival of 19.16 quality-adjusted life-months
      and 213 CMV cases per 1000 patients. Targeted preemptive therapy with orally
      administered valganciclovir increases costs and duration of survival to $46,900
      and 19.63 quality-adjusted life-months, respectively. CMV cases decrease to 174
      per 1000 patients. The cost per quality-adjusted life-year gained is $59,000.
      This result compares favorably with other strategies in end-stage HIV disease but
      hinges on valganciclovir cost and efficacy assumptions and the absence of
      minimally effective salvage antiretroviral therapy for HIV. The upcoming trial
      should resolve the clinical uncertainty surrounding some of these assumptions.

PMID- 11229848
TI  - Pneumococcal disease among human immunodeficiency virus-infected persons:
      incidence, risk factors, and impact of vaccination.
AB  - To determine the factors associated with pneumococcal disease (pneumococcal
      pneumonia or invasive disease) and the impact of pneumococcal vaccine in HIV
      infected persons, we analyzed patient data collected by the Adult and Adolescent
      Spectrum of HIV Disease Project for person-time between January 1990 and December
      1998. Among 39,086 persons with 71,116 person-years (py) of observation, 585
      episodes of pneumococcal disease were diagnosed (incidence, 8.2 episodes per 1000
      py). Factors associated with an increased risk for pneumococcal disease (P < .05)
      included injection drug use (adjusted relative risk [RR], 1.5) and blood
      transfusion (RR, 2.0) as the mode of HIV transmission (referent, male-male sex);
      black race/ethnicity (RR, 1.5; referent, white race); history of acquired
      immunodeficiency syndrome (AIDS)-defining opportunistic illness (RR, 2.1); a
      CD4(+) cell count of 200-499 cells/microL (RR, 2.5) or < 200 cells/microL (RR,
      3.7; referent, CD4(+) cell count of > or = 500 cells/microL); and alcoholism (RR,
      2.0). Factors associated with a decreased risk included prescription of
      antiretroviral therapy (RR for monotherapy, 0.6; for dual therapy, 0.7; for
      triple therapy, 0.5) and pneumococcal vaccination (RR for persons vaccinated at a
      CD4(+) cell count of > or = 500 cells/microL, 0.5). We recommend that
      pneumococcal vaccine be given to HIV-infected persons before profound
      immunosuppression has occurred.

PMID- 11229849
TI  - Safety of 2 recombinant human immunodeficiency virus type 1 (HIV-1) envelope
      vaccines in neonates born to HIV-1-infected women.
AB  - To determine the safety of 2 candidate vaccines against human immunodeficiency
      virus type 1 (HIV-1), a randomized, placebo-controlled, multicenter trial
      compared low, medium, and high doses of the vaccines or an adjuvant among infants
      born to HIV-infected women. No local or systemic reactions of grade 2 or greater
      were reported 48 h after the subjects underwent immunization. Grade 3 or 4
      chemistry toxicities occurred in 5 (3%) and grade 3 or 4 hematologic toxicities
      in 17 (11%) of 154 vaccinated subjects (not significantly different from 29
      adjuvant recipients). CD4(+) cell percentages of < or = 20% occurred at least
      once in 9 vaccinated subjects and 1 control subject. Sustained CD4(+) cell
      percentages of < or = 20% occurred in 4 HIV-infected children. Fourteen infants
      (8%) were confirmed to be HIV-infected; median CD4(+) cell counts among these
      children were 2074, 1674, 1584, and 821 cells/mm(3) at birth and weeks 24, 52,
      and 104, respectively. Thus, both vaccines were safe and well tolerated in
      neonates, and there was no evidence of accelerated immunologic decline in HIV
      infected infants.

PMID- 11229851
TI  - Recurrences of cytomegalovirus retinitis in a human immunodeficiency virus
      infected patient, despite potent antiretroviral therapy and apparent immune
      reconstitution.
AB  - We describe a 42-year-old man with human immunodeficiency virus infection who
      developed multiple recurrences of cytomegalovirus (CMV) retinitis despite
      receiving highly active antiretroviral therapy and having apparent immune
      reconstitution as evidenced by CD4(+) T lymphocyte counts of > 200 cells/mm(3).
      Laboratory investigation during one recurrence of retinitis confirmed that there
      was active CMV replication in the plasma and vitreous fluid. In addition,
      lymphoproliferative responses to CMV antigens were absent despite evidence of
      reactivity to Candida antigen and pokeweed mitogen. The clinical significance of
      this case and of other recently reported cases is discussed.

PMID- 11229850
TI  - Screening for sexually transmitted diseases in human immunodeficiency virus
      positive patients in Peru reveals an absence of Chlamydia trachomatis and
      identifies Trichomonas vaginalis in pharyngeal specimens.
AB  - To determine the prevalence of sexually transmitted diseases (STDs), we screened
      107 human immunodeficiency virus-positive patients in Peru, where the virus is
      predominantly sexually transmitted. Patients had multiple risk factors for STDs,
      and 38% of women and 50% of men had at least 1 STD (gonorrhea, trichomoniasis,
      herpes simplex, anogenital warts, or syphilis seropositivity). No chlamydial
      infection was detected, even though infection rates in the general population are
      5%-12%. Patients receiving trimethoprim-sulfamethoxazole(TMP-SMZ) for prophylaxis
      or treatment of respiratory infections were least likely to have cervicitis
      and/or urethritis (odds ratio, 0.37; 95% confidence interval, 0.15-0.89).
      Although not optimal treatment, administration of TMP-SMZ is effective against
      chlamydial infection. We speculate that the use of concomitant medications, such
      as TMP-SMZ, may be inadvertently preventing chlamydial infection in this
      population. Another finding was the presence of Trichomonas vaginalis in
      pharyngeal specimens of 3 men with histories of orogenital activity. This has not
      been previously reported and requires further study.

PMID- 11229852
TI  - Transepithelial intestinal excretion of ciprofloxacin in humans.
AB  - The excretion of ciprofloxacin in the small bowel was studied in 40 patients
      undergoing bowel surgery. Ciprofloxacin (200 mg) was administered iv, and
      intestinal samples were collected over a 120-min period. In ileal loops
      ciprofloxacin concentrations reached a peak of 4.0 mg/L, whereas in caecal fluid
      samples, concentrations were < 0.16 mg/L. Ciprofloxacin administered directly
      into the ileal and caecal loops did not result in measurable blood levels for 2
      h. The results confirm that ciprofloxacin is selectively excreted into the small
      bowel.

PMID- 11229853
TI  - Evaluation of Binax NOW, an assay for the detection of pneumococcal antigen in
      urine samples, performed among pediatric patients.
AB  - In our evaluation of a new assay for the detection of pneumococcal antigen in
      urine (Binax NOW; Binax), the test result was no more likely to be positive among
      88 children with radiographically confirmed pneumonia than among 198 control
      subjects; however, it was significantly more likely to be positive among children
      who were nasopharyngeal carriers of pneumococci. This test is not likely to be
      useful for distinguishing children with pneumococcal pneumonia from those who are
      merely colonized.

PMID- 11229854
TI  - Effectiveness of gloves in the prevention of hand carriage of vancomycin
      resistant enterococcus species by health care workers after patient care.
AB  - Gloving reduces acquisition of vancomycin-resistant Enterococcus species (VRE) on
      the hands, and it should be considered for routine inpatient care, even for
      contact with the intact skin of patients who may be colonized with VRE. However,
      gloving does not completely prevent contamination of the hands, and hand washing
      is necessary after glove removal.

PMID- 11229855
TI  - Treatment of chronic hepatitis C with amantadine hydrochloride in patients who
      had not responded to previous treatment with interferon-alpha and/or ribavirin.
AB  - Seven women and 3 men infected with hepatitis C virus, all of whom had failed to
      respond to therapy with either IFN-alpha or IFN and ribavirin, were treated with
      200 mg/day of amantadine hydrochloride for 12 months. We found a significant
      decrease of serum ALT activity without any decrease in virus load. These results
      suggest that amantadine hydrochloride should not be used as monotherapy for
      patients who do not respond to treatment with IFN-alpha and/or ribavirin.

PMID- 11229856
TI  - Prediction of gram-negative bacteremia in patients with cancer and febrile
      neutropenia by means of interleukin-8 levels in serum: targeting empirical
      monotherapy versus combination therapy.
AB  - In a prospective observational study of 133 neutropenic episodes, interleukin
      (IL)-8 serum levels > 2000 pg/mL at the onset of fever had a sensitivity of 53%
      and a specificity of 97% as a predictor of gram-negative bacteremia (GNB;
      positive predictive value, 73%; negative predictive value, 94%). The rates of
      early death differed significantly between patients with high and those with low
      IL-8 levels (3/11 vs. 1/122; P< .01). Serum IL-8 levels at the onset of fever
      define a low-risk subgroup of patients who can safely be treated with
      monotherapy.

PMID- 11229857
TI  - Inactivated pronase as the cause of false-positive results of serum cryptococcal
      antigen tests.
AB  - Four patients who had acquired immunodeficiency syndrome and who were evaluated
      for headache within a 3-week period had false-positive results of serum
      cryptococcal antigen tests. This cluster of false-positive test results appeared
      to be due to inactivation of the pronase vial in the test kit, a cause that has
      not been reported previously.

PMID- 11229858
TI  - Effect of antipyretic drugs in children with malaria.
AB  - A comparison of different antipyretics in children with malaria showed a small
      effect of naproxen, but not of metamizol, on the reduction of fever peaks.
      Antipyretic treatment had no effect on fever clearance and therefore should be
      used cautiously in the treatment of malaria.

PMID- 11229859
TI  - Antibodies to Toxoplasma gondii in individuals with first-episode schizophrenia.
AB  - We employed enzyme immunoassay (EIA) and Western blotting techniques to measure
      the level of antibodies to Toxoplasma gondii proteins in serum samples from 38
      individuals undergoing their first episode of schizophrenia and from a group of
      matched control subjects. We found that the individuals with first-episode
      schizophrenia had significantly increased levels of IgG, IgM, and IgA class
      antibodies to Toxoplasma proteins, as compared with the control subjects.

PMID- 11229860
TI  - Immunoresititution disease in relation to infection with Mycobacterium avium
      complex and to leprosy.

PMID- 11229862
TI  - Seroepidemiology of pertussis in senior adults.

PMID- 11229863
TI  - Severe hepatic injury associated with lipid formulations of amphotericin B.
AB  - A 14-year-old girl with leukemia had Doppler ultrasound evidence of hepatic
      necrosis, thought to be caused by a lipid formulation of amphotericin B, which
      has not been previously reported. It seems prudent to exert caution when
      retreating patients with previous hepatocellular damage with lipid formulations
      of amphotericin B.

PMID- 11229864
TI  - Spinal epidural lipomatosis in a human immunodeficiency virus-positive patient
      receiving steroids and protease inhibitor therapy.
AB  - We describe a patient who became cushingoid as a result of receiving steroid
      therapy for thrombocytopenia purpura and who then developed spinal epidural
      lipomatosis 4 months after he started receiving ritonavir as part of his therapy
      for human immunodeficiency virus infection. We believe that ritonavir may have
      contributed to the development of epidural lipomatosis and that clinicians should
      be aware of this possible association.

PMID- 11229865
TI  - Gonococcemia associated with fatal septic shock.
AB  - Gonococcal infection can be associated with septic shock leading to multiple
      organ failure and death.

PMID- 11229866
TI  - Progressive disseminated aspergillosis in a bone marrow transplant recipient:
      response with a high-dose lipid formulation of amphotericin B.
AB  - We present a case of progressive disseminated aspergillosis that involved
      multiple sites in a bone marrow transplant recipient with severe, chronic graft
      versus-host disease. The patient failed to respond to treatment with a
      conventional dosage of a lipid formulation of amphotericin B (lifoAmB; 5
      mg/kg/day) given alone or in combination with itraconazole, and he responded only
      to an aggressive strategy that included a very high dosage of lifoAmB (15
      mg/kg/day) given in combination with itraconazole as well as a rapid reduction in
      immunosuppression. Despite the patient's abnormal baseline kidney function, the
      very high doses of lifoAmB were well tolerated and did not result in additional
      renal toxicity.

PMID- 11229867
TI  - Neonatal sepsis by Campylobacter jejuni: genetically proven transmission from a
      household puppy.
AB  - We report a case of neonatal Campylobacter jejuni sepsis in a 3-week-old infant
      who acquired the infection through transmission from a recently acquired
      household puppy. Genotyping of Campylobacter strains obtained from puppy and
      child resulted in highly homogeneous findings. This represents the first
      genetically proven C. jejuni dog-human transmission.

PMID- 11229868
TI  - Members of the low density lipoprotein receptor family control diverse
      physiological processes.
AB  - The low density lipoprotein receptor (LDLR) family is a group of receptors that
      mediate endocytosis leading to lysosomal degradation of an enormous repertoire of
      ligands. To date, over 50 distinct macromolecules have been shown to bind members
      of the family. This wide spectrum of ligand recognition is the basis for an
      immense diversity in physiological processes in which these receptors
      participate. In this article, the physiological roles of the LDLR family members
      are briefly reviewed and a comprehensive list of the ligands with which the
      receptors interact is presented.

PMID- 11229869
TI  - Where do Alzheimer's plaques and tangles come from? Aging-induced protein
      degradation inefficiency.
AB  - Amyloid plaques and neurofibrillary tangles are prominent lesions in the aging
      brain and they may be responsible for cell death in Alzheimer's disease. But a
      basic question has not been answered: why and how are plaques and tangles formed
      during aging? In this study, we approach this question by first examining what
      happens in the aging body. Plaques and tangles do not come alone, but together
      with many other aging markers in the body (cholesterol deposition, gallstones,
      hair graying, and bone loss, etc.). Because these aging markers occur to a
      certain extent in all elderly and at about the same time in life, it is
      reasonable to conceive that they originate from a common cause, that is, aging
      induced metabolic inefficiency. If cholesterol and gallstone depositions are the
      results of inefficient degradation/clearance of lipids and minerals, then
      similarly plaque and tangle formation in most people would be the results of
      inefficient normal degradation of ?-amyloid precursor protein (APP) and tau,
      respectively. By this view, our studies should focus on the enzymes responsible
      for APP and tau normal degradation and their natural changes in aging, rather
      than on presumed pathological factors. Whatever precise mechanisms underlying
      their depositions, plaques and tangles are the natural products of aging, thus
      fundamentally different from pathological events such as cancer growth in
      concept.

PMID- 11229870
TI  - Mouse models of hyperlipidemia and atherosclerosis.
AB  - The mouse is the most utilized model to study lipids and atherosclerosis. Before
      the advent of the techniques of genetic manipulation it was well known that
      different inbred strains had varying degrees of susceptibility to diet-induced
      atherosclerosis. The C57BL/6 mouse was adopted as the standard even though the
      arterial lesions induced by even extreme diets were limited in size, complexity,
      and distribution. This changed with the production of several gene knockout and
      transgenic mice, which in many cases produced remarkable effects on plasma
      lipoproteins and arterial lesions even without dietary manipulations. The most
      typical example remains the apoE deficient model, in which a massive
      hyperlipidemia is accompanied with the development of severe atherosclerotic
      plaques at the aortic root and throughout the aortic tree. With the creation of
      the LDL receptor knockout, and the different knockout and transgenic mice with
      changes in apoB, apoE, and the HDL system, a solid body of new information has
      emerged on the mechanisms regulating plasma lipoprotein levels and controlling
      the initial stages of atherogenesis. This paper presents an overview of the most
      utilized mouse models and a summary of the results obtained with the technique of
      bone marrow transplantation, an approach to study macrophages in atherosclerosis.

PMID- 11229871
TI  - Lipoprotein lipase: physiology, biochemistry, and molecular biology.
AB  - Lipoprotein lipase (LpL) is the primary enzyme responsible for conversion of
      lipoprotein triglyceride into free fatty acids and monoglyderides. This permits
      their uptake into muscle and adipose. The roles of this enzyme in normal and
      altered physiology are reviewed. In addition, the relationship of LpL activity
      and genetic variations of LpL and human disease are summarized.

PMID- 11229872
TI  - Structural, biochemical and signaling properties of the low-density lipoprotein
      receptor gene family.
AB  - The low-density lipoprotein (LDL) receptor (LDL-R) family members (LDL-R, LRP,
      megalin, VLDL-R, apoER2) bind several extra-cellular structurally dissimilar
      ligands and internalize them for degradation by lysosomes by a process called
      receptor-mediated endocytosis. The receptor-mediated endocytosis involves
      immobilization of circulating ligands onto the cell-surface followed by their
      internalization and degradation. All the receptors can perform both of these
      functions. However, in the majority of the cases, other proteins immobilize
      ligands on to the cell-surface and subsequent internalization is mediated by
      these receptors. The LDL-R and LRP play important roles in plasma cholesterol
      homeostasis and fetal development. Megalin is an antigenic determinant for
      Heymann nephritis in rats and may be important for re-absorption of various
      molecules by the kidney. VLDL-R homologue in chicken is essential for female
      fertility. This receptor and apoER2 are critical for the proper development of
      the brain in mice. The members of the LDL-R gene family contain several
      complement-type and EGF precursor-like repeats, and single transmembrane and
      cytoplasmic domain. Cysteine-rich complement-type repeats containing DxSDE
      sequences at the C-termini constitute ligand-binding domains. In contrast to the
      ligand binding domains, receptor-binding domains in different ligands do not
      share sequence homology. It has been proposed that positive electrostatic surface
      potentials, not the primary sequences, in different ligands constitute receptor
      binding domains. The EGF precursor homology repeats in receptors are important
      for the dissociation of ligands from receptors in endocytic vesicles. The
      transmembrane domain is necessary for anchoring to membranes and the cytoplasmic
      domain is required for their targeting to coated pits and subsequent
      internalization. The receptor-mediated endocytosis involves recognition of the
      NPXY motif by clathrin. Recently, this motif has also been implicated in
      signaling pathways that are crucial in brain development. The signaling process
      involves the recognition of the NPXY motif by Disabled-1 protein and possibly
      other proteins involved in intracellular signaling cascade. The LDL-R gene family
      has provided important insights into the mechanisms of ligand catabolism and may
      serve as new targets for the treatment of different cardiovascular and neuronal
      disorders. In the future, their role in signaling may provide novel insights into
      brain development and neuronal layering.

PMID- 11229873
TI  - Signposts in the assembly of chylomicrons.
AB  - Intestinal cells synthesize and secrete chylomicrons in the postprandial state.
      Synthesis of these particles is defective in abetalipoproteinemia and chylomicron
      retention disease. Chylomicrons are very large, heterogeneous, lipid-rich
      particles ranging in diameters from 75 to 450 nm and function to transport
      dietary fat and fat-soluble vitamins to blood. The size heterogeneity of the
      secreted particles depends on the rate of fat absorption, type and amount of fat
      absorbed. The fatty acid composition of triglycerides present in chylomicrons
      reflects the composition of dietary fat, whereas the fatty acid composition of
      chylomicron phospholipids does not. The differences in the fatty acid
      compositions are also observed when lipids are labeled with glycerol. Thus, the
      differences are not due to differential incorporation of dietary fatty acids into
      different lipids but are mainly due to different pools of lipids used for
      chylomicron assembly. It has been suggested that preformed phospholipids and
      nascent triglycerides are preferentially used for intestinal lipoprotein
      assembly. Biosynthesis of chylomicrons requires apoB48. ApoB48 is translated from
      apoB mRNA that is post-transcriptionally edited in the intestinal cells to
      incorporate a stop codon. Nascent apoB48 may be cotranslationally lipidated and
      this process is critically dependent on the presence of microsomal triglyceride
      transfer protein. Two different models have been proposed for the assembly of
      chylomicrons. In the independent model, intestinal cells are hypothesized to
      synthesize VLDL and chylomicron by two independent pathways. The chylomicron
      assembly pathway is hypothesized to be sensitive to a surfactant, Pluronic L81,
      but that of VLDL assembly is not. In the sequential assembly model, synthesis of
      all lipoproteins is hypothesized to begin with the assembly of apoB-containing
      primordial lipoprotein particles. The primordial particles are suggested to fuse
      with triglyceride-rich lipid droplets that are synthesized independently of apoB.
      This process results in the core expansion of primordial particles and the
      synthesis of nascent lipoproteins. Differences in the size of secreted
      lipoproteins may be due to differences in the size of triglyceride-rich lipid
      droplets. Pluronic L81 is hypothesized to inhibit the formation of large
      triglyceride-rich droplets that serve as precursors for chylomicron assembly. In
      this review, we have discussed some signposts that might be unique to different
      steps in the assembly of chylomicrons. First, it is proposed that the association
      of preformed phospholipids with nascent apoB in the endoplasmic reticulum may
      serve as a signpost for the very early steps in the assembly of chylomicrons.
      Second, association of large amounts of newly synthesized triglycerides compared
      to preformed triglycerides may serve as a signpost for the assembly of larger
      lipoproteins. Third, the incorporation of retinyl esters may serve as markers for
      the final stages of chylomicron assembly. These signposts may be helpful in the
      identification and characterization of various intermediates in the assembly of
      chylomicrons. The knowledge about the molecular assembly of chylomicrons may lead
      to better therapeutic agents for controlling various hyperlipidemias, obesity,
      and atherosclerosis.

PMID- 11229874
TI  - Mitochondrial uncoupling protein 3 (UCP3) in skeletal muscle.
AB  - Mitochondrial uncoupling protein (UCP), mitochondrial transporters, function as a
      proton channel and increase thermogenesis. UCP1 is expressed in brown adipose
      tissues (BAT), UCP2 is widely expressed in multiple tissues, while UCP3 is
      expressed in skeletal muscle. Thus, UCPs, especially UCP3, in skeletal muscles is
      a good candidates for prevention of obesity and diabetes. However, the role of
      UCP3 in skeletal muscle for energy expenditure and obesity has been
      controversial. There is some evidence that the UCP3 is possibly regulated by
      energy substrate, such as lipid and glucose. These observations suggest that
      increased energy substrate entry in muscle results in an increase in UCP3
      expression which leads to an increase in energy expenditure.

PMID- 11229875
TI  - Macrophage foam cells and atherosclerosis.
AB  - Focal buildup of cholesterol in arteries is the process that produces
      atherosclerotic plaques, the cause of most coronary artery disease and strokes.
      Monocyte-derived macrophages are central cells that accumulate this cholesterol
      in atherosclerotic lesions, a manifestation of the scavenging function of the
      macrophage. Different types of cholesterol-containing lipid particles found in
      atherosclerotic lesions may enter macrophages by a variety of endocytic pathways.
      The fate of cholesterol that enters macrophages determines whether macrophages
      help or hinder cholesterol removal from the vessel wall. Macrophages may function
      to carry cholesterol out of lesions, or to process the cholesterol for excretion
      in association with small protein-phospholipid complexes. Alternatively,
      macrophages that do not efficiently function to remove cholesterol from lesions
      may ultimately undergo cell death. Some cytokines, hormones, and pharmacologic
      agents show potential to modulate these processes and may be useful in directing
      macrophage function in atherosclerotic lesions towards beneficial rather than
      harmful effects.

PMID- 11229876
TI  - Intestinal lipid absorption and transport.
AB  - The purpose of this review is to update the reader on our current knowledge of
      the digestion, uptake, and transport of dietary lipid. In particular, it
      discusses how intestinal lipid transporters may play a role in the uptake of
      lipids by the enterocytes, and how chylomicrons are formed in the enterocytes and
      packaged for export into the lymphatic system through exocytosis. The
      classification and properties of lipids is first described followed by a
      discussion of structured lipids and their role in human nutrition. Digestion of
      triacylglycerols takes place in the stomach aided by the enzyme gastric lipase.
      The origin and properties of lingual and gastric lipase are reviewed. Most
      digestion of triacylglycerols by pancreatic lipase occurs in the intestinal
      lumen. Similarly, digestion of cholesteryl ester and phospholipids also takes
      place in the intestinal lumen. This review describes in considerable detail the
      uptake of lipid digestion products by the enterocytes, particularly the role of
      recently identified lipid transporters. The intracellular trafficking and the
      resynthesis of complex lipids from the lipid digestion products are talked about,
      particularly within the context of the recently generated knockout mouse that
      lacks the key lipid reesterification enzymes. Finally, the mechanisms of the
      formation and secretion of chylomicrons is described and clinical disorders
      discussed.

PMID- 11229877
TI  - Gene targeting in hemostasis. plasminogen.
AB  - A number of in vitro and in vivo observations have implicated plasminogen in
      contributing to events associated with diverse physiological and
      pathophysiological processes. The development of gene knockout technology has led
      to the generation of plasminogen deficient mice. These mice survive to adulthood
      and are thus a valuable resource for directly assessing its role in these
      processes. As a result, fibrinolytic and nonfibrinolytic functions have been
      identified from studies in which these mice were challenged utilizing a number of
      models that mimic both normal biological and pathological events.

PMID- 11229878
TI  - Apolipoprotein(a): structure and biology.
AB  - Apolipoprotein(a), apo(a), the distinctive glycoprotein constituent of
      lipoprotein(a), Lp(a), is synthesized in the liver, links covalently to apoB100
      lipoprotein, and travels so linked in the plasma to tissue sites where removal
      mechanisms are yet undetermined. Depending on the redox status of the surrounding
      milieu, apo(a) may re-acquire its unbound state shown to have structural and
      functional properties different from those of the bound form. Apo(a) is
      potentially athero-thrombogenic, a property which may be influenced by its size,
      sequence polymorphism, type of lipoprotein it is linked to and the inflammatory
      state of the vessel wall. This set of variables must be taken into account when
      assessing the cardiovascular pathogenicity of free and bound apo(a).

PMID- 11229879
TI  - ABC transporters and cholesterol metabolism.
AB  - ATP-binding cassette (ABC) proteins form a group of highly conserved cellular
      transmembrane transporters. Studies over the past year have implicated ABC
      transporters in cellular lipid trafficking processes. This notion has recently
      been confirmed and extended by the finding that the ABC transporter ABCA1 is a
      key regulator of high-density lipoprotein (HDL) metabolism and macrophage
      targeting to the RES or the vascular wall. Expression of a large number of ABC
      transporters in monocytes/macrophages and their regulation by cholesterol flux
      render these transporter molecules potentially critical players in chronic
      inflammatory diseases such as atherosclerosis.

PMID- 11229880
TI  - Lipoprotein subclasses and atherosclerosis.
AB  - Differences in LDL and HDL subclass distribution contribute to increased CAD risk
      through a variety of mechanisms. The inherited disorder characterized by an
      abundance of small, dense LDL particles increased CAD risk 3-fold and is
      associated with rapid arteriographic progression. The metabolic milieu associated
      with the small LDL trait includes insulin resistance, increased IDL, increased
      susceptibility to oxidative damage, impaired reverse cholesterol transport, and
      increased post prandial lipemia. Recent evidence indicates that the LDL IIIa+b
      region are the LDL subclass regions most associated with atherosclerosis.
      Improvement in LDL subclass distribution has been associated with arteriographic
      improvement significantly more than LDLC change. Therapeutic treatments including
      diet, and many pharmacologic interventions have a differential response in
      subjects characterized by an abundance of either small, or large LDL particles.
      Individual patient information regarding LDL and HDL subclass distribution can be
      used to improve medical management of the CAD patient that results in improved
      outcomes.

PMID- 11229881
TI  - Apolipoprotein E: a cholesterol transport protein with lipid transport
      independent cell signaling properties.
AB  - Apolipoprotein (apo) E is a 34-kDa glycoprotein associated with plasma
      lipoproteins. In contrast to other apolipoproteins, apoE is expressed
      ubiquitously in all tissues and appears to have a wide variety of functions in
      addition to lipid transport. Although the lipid transport properties of apoE are
      well characterized, the appreciation apoE functions other than lipid transport is
      still in an infancy stage. Nevertheless, there is increasing evidence that apoE
      regulates cell functions in a variety of tissues and organs. This review article
      summarizes briefly the current status of our understanding on the lipid transport
      independent properties of this apolipoprotein.

PMID- 11229882
TI  - CD8+ T cell mediated noncytolytic inhibition of human immunodeficiency virus type
      I.
AB  - The development of cellular immune responses in primary human immunodeficiency
      virus type-1 (HIV-1) infection is accompanied by a dramatic decrease in plasma
      viremia and resolution of the acute clinical syndrome. The full nature of the
      immunological response and its consequences on HIV pathogenesis is still largely
      a mystery, but significant progress has been achieved in the characterization of
      some of the players involved. Several studies indicate that noncytolytic HIV
      suppression by CD8+ T lymphocytes may be inversely associated with viral load
      suggesting that this antiviral activity is important in host control of HIV
      replication. This review focuses on this antiviral activity by CD8+ T
      lymphocytes, which is distinct from that activity elicited by some cytolytic CD8+
      T lymphocytes (CTLs).

PMID- 11229883
TI  - Fetal lipid metabolism.
AB  - The fetus grows at a rate unparalleled by that during any other stage of life. To
      maintain its rapid growth rate, the fetus requires a significant amount of
      cholesterol and fatty acids. For structural purposes alone, the fetus requires
      1.5 mg of cholesterol per gram of tissue, not including the brain. Cholesterol is
      also required as a precursor for various steroidogenic hormones that are critical
      to normal development, such as estrogen, and for metabolic regulators, such as
      oxysterols. More recently, it was found that cholesterol is necessary for the
      activation of Sonic hedgehog (Shh) (1), an organizer involved in early spatial
      patterning of the forebrain (2). Fatty acids are needed as structural components
      of tissues, as a source of energy, and if metabolic regulation in the fetus is
      similar to that in the adult, as activators of transcription factors. The fetus,
      as in any tissue, acquires its cholesterol and fatty acids from two different
      sources, endogenous and exogenous.

PMID- 11229884
TI  - Roles of plasma lipid transfer proteins in reverse cholesterol transport.
AB  - Plasma lipid transfer proteins include plasma cholesteryl ester transfer protein
      (CETP) and phospholipid transfer protein (PLTP). Plasma CETP facilitates the
      transfer of cholesteryl ester (CE) from high-density lipoprotein (HDL) to
      apolipoprotein (apo) B-containing lipoproteins, and is a key protein in reverse
      cholesterol transport which protects vessel walls from atherosclerosis. The
      importance of plasma CETP in lipoprotein metabolism was highlighted by the
      discovery of CETP-deficient subjects with a marked hyperalphalipoproteinemia
      (HALP). The deficiency of CETP causes various abnormalities in the concentration,
      composition, and functions of both HDL and low-density lipoprotein (LDL).
      Although the significance of CETP in terms of atherosclerosis has been
      controversial, the in vitro evidence showed that large CE-rich HDL particles in
      CETP deficiency are defective in cholesterol efflux. Recent epidemiological
      studies in Japanese-Americans and in Omagari area where HALP subjects with the
      intron 14 splicing defect of CETP gene are markedly frequent, have demonstrated
      an increased incidence of coronary atherosclerosis in CETP-deficient patients.
      Similarly, scavenger receptor BI (SR-BI) knockout mice show a marked increase in
      HDL-cholesterol but accelerated atherosclerosis in atherosclerosis-susceptible
      mice. Thus, CETP deficiency is a state of impaired reverse cholesterol transport
      which may possibly lead to the development of atherosclerosis. PLTP transfers
      phospholipids from triglyceride (TG)-rich lipoproteins to HDL during lipolysis.
      Human plasma PLTP has a 20% sequence homology to human CETP and human PLTP gene
      has a marked similarity in the exon-intron organization. Both CETP and PLTP
      belong to the lipid transfer/lipopolysaccharide binding protein (LBP) gene
      family, which also includes LBP and bactericidal/permeability-increasing protein
      (BPI). Although these 4 proteins possess different physiological functions, they
      share marked biochemical similarities. The current review will also focus on the
      molecular genetics and function of plasma lipid transfer proteins, including CETP
      and PLTP.

PMID- 11229885
TI  - Postprandial lipoproteins and atherosclerosis.
AB  - During the postprandial state, dietary lipid is transported from the intestine to
      peripheral tissues by plasma lipoproteins called chylomicrons. In the capillary
      beds of peripheral tissues, chylomicron triglycerides are lipolyzed by the
      enzyme, lipoprotein lipase, allowing the delivery of free fatty acids to the
      cells. As a result, this produces a new particle of smaller size and enriched
      with cholesteryl ester referred to as chylomicron remnants. These particles are
      rapidly removed from the blood primarily by the liver. The liver has a complex
      chylomicron remnant removal system which is comprised of a combination of
      different mechanisms that include the low-density-lipoprotein receptor (LDLR) and
      the LDLR-related-protein (LRP). Furthermore, it has been suggested that there is
      a sequestration component whereby chylomicron remnants bind to heparan sulfate
      proteoglycans (HSPG) and/or hepatic lipase; this is then followed by transport to
      one or both of the above receptors for hepatic uptake. Over the years, a major
      concern has arisen about the association of chylomicron remnants and coronary
      heart disease (CHD) in man. Slow removal of chylomicron remnants, as reflected by
      a prolonged postprandial state, is now commonly observed in patients with CHD and
      those that have abnormal lipid disorders such as hypertriglyceridemia, familial
      hypercholesterolemia, familial combined hyperlipidemia and non-insulin-dependent
      diabetes-mellitus. The present review will focus on (a) the details of the
      metabolic pathway (exogenous pathway) that describes the two-step processing of
      postprandial lipoproteins, (b) the role of the liver, the receptors, and the
      importance of efficient removal of chylomicron remnants from the blood
      circulation, and (c) the potential atherogenic effects of chylomicron remnants on
      the arterial wall.

PMID- 11229886
TI  - Transcriptional regulation of the human apolipoprotein genes.
AB  - This review provides experiments and putative mechanisms which underlie the
      transcription of the human apolipoprotein genes in vitro and in vivo. Summarized
      below are the key findings for individual genes and gene clusters. ApoA-II. 1-
      The -911/+29 promoter is sufficient to direct expression of a reporter gene
      exclusively in the liver and thus represents a liver-specific promoter. 2-
      Important factors for the activity of this promoter are hormone nuclear receptors
      and the ubiquitous factor USF. 3. SREBP-1 and SREBP-2 bind to five and four sites
      respectively and transactivate the apoA-II promoter. Their role in the in vivo
      transcription of the apoA-II gene has not been established. ApoB. 1. Regulatory
      sequence extending 5 Kb upstream and 1.5 Kb downstream of the apoB promoter are
      sufficient to direct hepatic expression of the apoB gene. The intestinal
      expression of the apoB gene requires in addition a 315 bp intestinal enhancer
      located 56 Kb upstream of the apoB gene. 2. Important factors for apoB gene
      transcription appear to be C/EBP, HNF-3, HNF-4 and other nuclear receptors which
      bind both on the proximal promoter and the intestinal enhancer.
      ApoE/ApoCI/ApoCIV/ApoCII Cluster. 1. The expression of the genes of the
      apoE/apoCI/apoCII/apoE cluster are controlled by two homologous hepatic control
      regions designated HCR-1 and HCR-2 of approximately 600 bp located 15 and 27 Kb
      3? of the apoE gene. Either region is sufficient to direct gene expression in
      vivo, although HCR-1 appears to have a dominant effect on apoE and apoCI and HCR
      2 has a dominant effect on apoCIV and apoCII gene expression. 2. Two other
      homologous regulatory regions designated ME-1 and ME-2 located 3.3 and 15.9 Kb
      downstream of the apoE gene can direct independently the expression of the apoE
      gene in macrophages and adipocytes. 3. Important factors for apoE gene regulation
      appear to be SP1 on the proximal promoter, and possibly HNF-3, C/EBP and hormone
      nuclear receptors on the enhancers. 4. Important factors for apoCII gene
      transcription appear to be HNF-4 and RXR-alpha/T3R-beta which binds to a thyroid
      response element of the proximal promoter. ApoA-I/ApoCIII/ApoA-IV Gene Cluster.
      1. The transcription of the apoA-I/apoCIII/apoA-IV gene cluster is controlled by
      a common enhancer located 590 to 790 nucleotides upstream of the apoCIII gene. 2.
      Important factors for the activity of the enhancer are SP1, HNF-4 and possibly
      other nuclear receptors. Important factors for the activity of the proximal
      promoters are HNF-4, and possibly other nuclear receptors. 3. The HNF-4 binding
      site of the apoCIII enhancer is required for the intestinal expression of apoA-I
      and apoCIII gene and enhances synergistically the hepatic transcription of the
      two genes and possibly of apoA-IV in vivo. The three SP1 sites of the enhancer
      are also required for the intestinal expression of apoA-I and apoCIII genes in
      vivo and for the enhancement of the hepatic transcription. 4. Pro-inflammatory
      cytokines such as TNF-alpha and IL-1 repress, and TGF-beta stimulates the apoCIII
      promoter activity. The TGF-beta pathway activates SMAD3/4 proteins which interact
      with HNF-4 bound to the apoCIII promoter and enhancer and increase its activity.
      5. It appears that other factors activated by different signaling pathways (NF
      kappa-B, Jun and others) interact with HNF-4 bound to the enhancer and thus
      repress the activity of apoCIII promoter. Understanding the transcriptional
      regulatory mechanism of the apolipoprotein genes may allow, in the long run,
      selective increase of anti-atherogenic lipoproteins and thus reduce the risk of
      cardiovascular disease.

PMID- 11229887
TI  - Protein trans-splicing to produce herbicide-resistant acetolactate synthase.
AB  - Protein splicing in trans has been demonstrated both in vivo and in vitro by
      biochemical and immunological analyses, but in vivo production of a functional
      protein by trans-splicing has not been reported previously. In this study, we
      used the DnaE intein from Synechocystis sp. strain PCC6803, which presumably
      reconstitutes functional DnaE protein by trans-splicing in vivo, to produce
      functional herbicide-resistant acetolactate synthase II (ALSII) from two unlinked
      gene fragments in Escherichia coli. The gene for herbicide-resistant ALSII was
      fused in frame to DnaE intein segments capable of promoting protein splicing in
      trans and was expressed from two compatible plasmids as two unlinked fragments.
      Cotransformation of E. coli with the two plasmids led to production of a
      functional enzyme that conferred herbicide resistance to the host E. coli cells.
      These results demonstrate the feasibility of expressing functional genes from two
      unlinked DNA loci and provide a model for the design of nontransferable
      transgenes in plants.

PMID- 11229888
TI  - Fungal metabolism of toluene: monitoring of fluorinated analogs by (19)F nuclear
      magnetic resonance spectroscopy.
AB  - We used isomeric fluorotoluenes as model substrates to study the catabolism of
      toluene by five deuteromycete fungi and one ascomycete fungus capable of growth
      on toluene as the sole carbon and energy source, as well as by two fungi
      (Cunninghamella echinulata and Aspergillus niger) that cometabolize toluene.
      Whole cells were incubated with 2-, 3-, and 4-fluorotoluene, and metabolites were
      characterized by (19)F nuclear magnetic resonance. Oxidation of fluorotoluene by
      C. echinulata was initiated either at the aromatic ring, resulting in fluorinated
      o-cresol, or at the methyl group to form fluorobenzoate. The initial conversion
      of the fluorotoluenes by toluene-grown fungi occurred only at the side chain and
      resulted in fluorinated benzoates. The latter compounds were the substrate for
      the ring hydroxylation and, depending on the fluorine position, were further
      metabolized up to catecholic intermediates. From the (19)F nuclear magnetic
      resonance metabolic profiles, we propose that diverse fungi that grow on toluene
      assimilate toluene by an initial oxidation of the methyl group.

PMID- 11229889
TI  - Identification of Bacillus thuringiensis subsp. kurstaki strain HD1-Like bacteria
      from environmental and human samples after aerial spraying of Victoria, British
      Columbia, Canada, with Foray 48B.
AB  - Aerial applications of Foray 48B, which contains Bacillus thuringiensis strain
      HD1, were carried out on 9 to 10 May, 19 to 21 May, and 8 to 9 June 1999 to
      control European gypsy moth (Lymantria dispar) populations in Victoria, British
      Columbia, Canada. A major assessment of the health impact of B. thuringiensis
      subsp. kurstaki was conducted by the Office of the Medical Health Officer of the
      Capital Health Region during this period. Environmental (air and water) and human
      (nasal swab) samples, collected before and after aerial applications of Foray
      48B, both in the spray zone and outside of the spray zone, were analyzed for the
      presence of strain HD1-like bacteria. Random amplified polymorphic DNA analysis,
      cry gene-specific PCR, and dot blot DNA hybridization techniques were used to
      screen over 11,000 isolates of bacteria. We identified bacteria with genetic
      patterns consistent with those of B. thuringiensis subsp. kurstaki HD1 in 9,102
      of 10,659 (85.4%) isolates obtained from the air samples, 13 of 440 (2.9%)
      isolates obtained from the water samples, and 131 of 171 (76.6%) isolates from
      the nasal swab samples. These analyses suggest that B. thuringiensis subsp.
      kurstaki HD1-like bacteria were present both in the environment and in the human
      population of Victoria prior to aerial applications of Foray 48B. The presence of
      B. thuringiensis subsp. kurstaki HD1-like bacteria in human nasal passages
      increased significantly after the application of Foray 48B, both inside and
      outside the spray zone.

PMID- 11229890
TI  - Microbial populations involved in cycling of dimethyl sulfide and methanethiol in
      freshwater sediments.
AB  - Although several microorganisms that produce and degrade methanethiol (MT) and
      dimethyl sulfide (DMS) have been isolated from various habitats, little is known
      about the numbers of these microorganisms in situ. This study reports on the
      identification and quantification of microorganisms involved in the cycling of MT
      and DMS in freshwater sediments. Sediment incubation studies revealed that the
      formation of MT and DMS is well balanced with their degradation. MT formation
      depends on the concentrations of both sulfide and methyl group-donating
      compounds. A most-probable number (MPN) dilution series with syringate as the
      growth substrate showed that methylation of sulfide with methyl groups derived
      from syringate is a commonly occurring process in situ. MT appeared to be
      primarily degraded by obligately methylotrophic methanogens, which were found in
      the highest positive dilutions on DMS and mixed substrates (methanol,
      trimethylamine [TMA], and DMS). Amplified ribosomal DNA restriction analysis
      (ARDRA) and 16S rRNA gene sequence analysis of the total DNA isolated from the
      sediments and of the DNA isolated from the highest positive dilutions of the MPN
      series (mixed substrates) revealed that the methanogens that are responsible for
      the degradation of MT, DMS, methanol, and TMA in situ are all phylogenetically
      closely related to Methanomethylovorans hollandica. This was confirmed by
      sequence analysis of the product obtained from a nested PCR developed for the
      selective amplification of the 16S rRNA gene from M. hollandica. The data from
      sediment incubation experiments, MPN series, and molecular-genetics detection
      correlated well and provide convincing evidence for the suggested mechanisms for
      MT and DMS cycling and the common presence of the DMS-degrading methanogen M.
      hollandica in freshwater sediments.

PMID- 11229891
TI  - Analysis of bacterial community structure in sulfurous-oil-containing soils and
      detection of species carrying dibenzothiophene desulfurization (dsz) genes.
AB  - The selective effects of sulfur-containing hydrocarbons, with respect to changes
      in bacterial community structure and selection of desulfurizing organisms and
      genes, were studied in soil. Samples taken from a polluted field soil (A) along a
      concentration gradient of sulfurous oil and from soil microcosms treated with
      dibenzothiophene (DBT)-containing petroleum (FSL soil) were analyzed. Analyses
      included plate counts of total bacteria and of DBT utilizers, molecular community
      profiling via soil DNA-based PCR-denaturing gradient gel electrophoresis (PCR
      DGGE), and detection of genes that encode enzymes involved in the desulfurization
      of hydrocarbons, i.e., dszA, dszB, and dszC. Data obtained from the A soil showed
      no discriminating effects of oil levels on the culturable bacterial numbers on
      either medium used. Generally, counts of DBT degraders were 10- to 100-fold lower
      than the total culturable counts. However, PCR-DGGE showed that the numbers of
      bands detected in the molecular community profiles decreased with increasing oil
      content of the soil. Analysis of the sequences of three prominent bands of the
      profiles generated with the highly polluted soil samples suggested that the
      underlying organisms were related to Actinomyces sp., Arthrobacter sp., and a
      bacterium of uncertain affiliation. dszA, dszB, and dszC genes were present in
      all A soil samples, whereas a range of unpolluted soils gave negative results in
      this analysis. Results from the study of FSL soil revealed minor effects of the
      petroleum-DBT treatment on culturable bacterial numbers and clear effects on the
      DBT-utilizing communities. The molecular community profiles were largely stable
      over time in the untreated soil, whereas they showed a progressive change over
      time following treatment with DBT-containing petroleum. Direct PCR assessment
      revealed the presence of dszB-related signals in the untreated FSL soil and the
      apparent selection of dszA- and dszC-related sequences by the petroleum-DBT
      treatment. PCR-DGGE applied to sequential enrichment cultures in DBT-containing
      sulfur-free basal salts medium prepared from the A and treated FSL soils revealed
      the selection of up to 10 distinct bands. Sequencing a subset of these bands
      provided evidence for the presence of organisms related to Pseudomonas putida, a
      Pseudomonas sp., Stenotrophomonas maltophilia, and Rhodococcus erythropolis.
      Several of 52 colonies obtained from the A and FSL soils on agar plates with DBT
      as the sole sulfur source produced bands that matched the migration of bands
      selected in the enrichment cultures. Evidence for the presence of dszB in 12
      strains was obtained, whereas dszA and dszC genes were found in only 7 and 6
      strains, respectively. Most of the strains carrying dszA or dszC were classified
      as R. erythropolis related, and all revealed the capacity to desulfurize DBT. A
      comparison of 37 dszA sequences, obtained via PCR from the A and FSL soils, from
      enrichments of these soils, and from isolates, revealed the great similarity of
      all sequences to the canonical (R. erythropolis strain IGTS8) dszA sequence and a
      large degree of internal conservation. The 37 sequences recovered were grouped in
      three clusters. One group, consisting of 30 sequences, was minimally 98% related
      to the IGTS8 sequence, a second group of 2 sequences was slightly different, and
      a third group of 5 sequences was 95% similar. The first two groups contained
      sequences obtained from both soil types and enrichment cultures (including
      isolates), but the last consisted of sequences obtained directly from the
      polluted A soil.

PMID- 11229892
TI  - Expression in Escherichia coli of native and chimeric phenolic acid
      decarboxylases with modified enzymatic activities and method for screening
      recombinant E. coli strains expressing these enzymes.
AB  - Four bacterial phenolic acid decarboxylases (PAD) from Lactobacillus plantarum,
      Pediococcus pentosaceus, Bacillus subtilis, and Bacillus pumilus were expressed
      in Escherichia coli, and their activities on p-coumaric, ferulic, and caffeic
      acids were compared. Although these four enzymes displayed 61% amino acid
      sequence identity, they exhibit different activities for ferulic and caffeic acid
      metabolism. To elucidate the domain(s) that determines these differences,
      chimeric PAD proteins were constructed and expressed in E. coli by exchanging
      their individual carboxy-terminal portions. Analysis of the chimeric enzyme
      activities suggests that the C-terminal region may be involved in determining PAD
      substrate specificity and catalytic capacity. In order to test phenolic acid
      toxicity, the levels of growth of recombinant E. coli displaying and not
      displaying PAD activity were compared on medium supplemented with different
      concentrations of phenolic acids and with differing pHs. Though these acids
      already have a slight inhibitory effect on E. coli, vinyl phenol derivatives,
      created during decarboxylation of phenolic acids, were much more inhibitory to
      the E. coli control strain. To take advantage of this property, a solid medium
      with the appropriate pH and phenolic acid concentration was developed; in this
      medium the recombinant E. coli strains expressing PAD activity form colonies
      approximately five times smaller than those formed by strains devoid of PAD
      activity.

PMID- 11229893
TI  - The effect of the Agrobacterium tumefaciens attR mutation on attachment and root
      colonization differs between legumes and other dicots.
AB  - Infections of wound sites on dicot plants by Agrobacterium tumefaciens result in
      the formation of crown gall tumors. An early step in tumor formation is bacterial
      attachment to the plant cells. AttR mutants failed to attach to wound sites of
      both legumes and nonlegumes and were avirulent on both groups of plants. AttR
      mutants also failed to attach to the root epidermis and root hairs of nonlegumes
      and had a markedly reduced ability to colonize the roots of these plants.
      However, AttR mutants were able to attach to the root epidermis and root hairs of
      alfalfa, garden bean, and pea. The mutant showed little reduction in its ability
      to colonize these roots. Thus, A. tumefaciens appears to possess two systems for
      binding to plant cells. One system is AttR dependent and is required for
      virulence on all of the plants tested and for colonization of the roots of all of
      the plants tested except legumes. Attachment to root hairs through this system
      can be blocked by the acetylated capsular polysaccharide. The second system is
      AttR independent, is not inhibited by the acetylated capsular polysaccharide, and
      allows the bacteria to bind to the roots of legumes.

PMID- 11229894
TI  - Chromate reduction by a pseudomonad isolated from a site contaminated with
      chromated copper arsenate.
AB  - A pseudomonad (CRB5) isolated from a decommissioned wood preservation site
      reduced toxic chromate [Cr(VI)] to an insoluble Cr(III) precipitate under aerobic
      and anaerobic conditions. CRB5 tolerated up to 520 mg of Cr(VI) liter(-1) and
      reduced chromate in the presence of copper and arsenate. Under anaerobic
      conditions it also reduced Co(III) and U(VI), partially internalizing each metal.
      Metal precipitates were also found on the surface of the outer membrane and
      (sometimes) on a capsule. The results showed that chromate reduction by CRB5 was
      mediated by a soluble enzyme that was largely contained in the cytoplasm but also
      found outside of the cells. The crude reductase activity in the soluble fraction
      showed a K(m) of 23 mg liter(-1) (437 microM) and a V(max) of 0.98 mg of Cr h(-1)
      mg of protein(-1) (317 nmol min(-1) mg of protein(-1)). Minor membrane-associated
      Cr(VI) reduction under anaerobiosis may account for anaerobic reduction of
      chromate under nongrowth conditions with an organic electron donor present.
      Chromate reduction under both aerobic and anaerobic conditions may be a
      detoxification strategy for the bacterium which could be exploited to
      bioremediate chromate-contaminated or other toxic heavy metal-contaminated
      environments.

PMID- 11229895
TI  - Different mechanisms of resistance to Bacillus thuringiensis toxins in the
      indianmeal moth.
AB  - Susceptibility to protoxin and toxin forms of Cry1Ab and the binding of (125)I
      labeled Cry1Ab and Cry1Ac has been examined in three Plodia interpunctella
      colonies, one susceptible (688(s)) and two resistant (198(r) and Dpl(r)) to
      Bacillus thuringiensis. Toxicological studies showed that the 198(r) colony was
      11-fold more resistant to Cry1Ab protoxin than to Cry1Ab activated toxin, whereas
      the Dpl(r) colony was 4-fold more resistant to protoxin versus toxin. Binding
      results with (125)I-labeled toxins indicated the occurrence of two different
      binding sites for Cry1Ab in the susceptible insects, one of them shared with
      Cry1Ac. Cry1Ab binding was found to be altered in insects from both resistant
      colonies, though in different ways. Compared with the susceptible colony, insects
      from the Dpl(r) colony showed a drastic reduction in binding affinity (60-fold
      higher K(d)), although they had similar concentrations of binding sites. Insects
      from the 198(r) colony showed a slight reduction in both binding affinity and
      binding site concentration (five-fold-higher K(d) and ca. three-fold-lower R(t)
      compared with the 688(s) colony). No major difference in Cry1Ac binding was found
      among the three colonies. The fact that the 198(r) colony also has a protease
      mediated mechanism of resistance (B. Oppert, R. Hammel, J. E. Throne, and K. J.
      Kramer, J. Biol. Chem. 272:23473-23476, 1997) is in agreement with our
      toxicological data in which this colony has a different susceptibility to the
      protoxin and toxin forms of Cry1Ab. It is noteworthy that the three colonies used
      in this work derived originally from ca. 100 insects, which reflects the high
      variability and high frequency of B. thuringiensis resistance genes occurring in
      natural populations.

PMID- 11229896
TI  - The Bacillus thuringiensis cyt genes for hemolytic endotoxins constitute a gene
      family.
AB  - In the same way that cry genes, coding for larvicidal delta endotoxins,
      constitute a large and diverse gene family, the cyt genes for hemolytic toxins
      seem to compose another set of highly related genes in Bacillus thuringiensis.
      Although the occurrence of Cyt hemolytic factors in B. thuringiensis has been
      typically associated with mosquitocidal strains, we have recently shown that cyt
      genes are also present in strains with different pathotypes; this is the case for
      the morrisoni subspecies, which includes strains biologically active against
      dipteran, lepidopteran, and coleopteran larvae. In addition, while one Cyt type
      of protein has been described in all of the mosquitocidal strains studied so far,
      the present study confirms that at least two Cyt toxins coexist in the more toxic
      antidipteran strains, such as B. thuringiensis subsp. israelensis and subsp.
      morrisoni PG14, and that this could also be the case for many others. In fact,
      PCR screening and Western blot analysis of 50 B. thuringiensis strains revealed
      that cyt2-related genes are present in all strains with known antidipteran
      activity, as well as in some others with different or unknown host ranges.
      Partial DNA sequences for several of these genes were determined, and protein
      sequence alignments revealed a high degree of conservation of the structural
      domains. These findings point to an important biological role for Cyt toxins in
      the final in vivo toxic activity of many B. thuringiensis strains.

PMID- 11229897
TI  - Molecular characterization of cryptosporidium oocysts in samples of raw surface
      water and wastewater.
AB  - Recent molecular characterizations of Cryptosporidium parasites make it possible
      to differentiate the human-pathogenic Cryptosporidium parasites from those that
      do not infect humans and to track the source of Cryptosporidium oocyst
      contamination in the environment. In this study, we used a small-subunit rRNA
      based PCR-restriction fragment length polymorphism (RFLP) technique to detect and
      characterize Cryptosporidium oocysts in 55 samples of raw surface water collected
      from several areas in the United States and 49 samples of raw wastewater
      collected from Milwaukee, Wis. Cryptosporidium parasites were detected in 25
      surface water samples and 12 raw wastewater samples. C. parvum human and bovine
      genotypes were the dominant Cryptosporidium parasites in the surface water
      samples from sites where there was potential contamination by humans and cattle,
      whereas C. andersoni was the most common parasite in wastewater. There may be
      geographic differences in the distribution of Cryptosporidium genotypes in
      surface water. The PCR-RFLP technique can be a useful alternative method for
      detection and differentiation of Cryptosporidium parasites in water.

PMID- 11229898
TI  - Emulsifying activities of purified Alasan proteins from Acinetobacter
      radioresistens KA53.
AB  - The bioemulsifier of Acinetobacter radioresistens KA53, referred to as alasan, is
      a high-molecular-weight complex of polysaccharide and protein. The emulsifying
      activity of the purified polysaccharide (apo-alasan) is very low. Three of the
      alasan proteins were purified by preparative sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and had apparent molecular masses of 16, 31,
      and 45 kDa. Emulsification assays using the isolated alasan proteins demonstrated
      that the active components of the alasan complex are the proteins. The 45-kDa
      protein had the highest specific emulsifying activity, 11% higher than the intact
      alasan complex. The 16- and 31-kDa proteins gave relatively low emulsifying
      activities, but they were significantly higher than that of apo-alasan. The
      addition of the purified 16- and 31-kDa proteins to the 45-kDa protein resulted
      in a 1.8-fold increase in the specific emulsifying activity and increased
      stability of the oil-in-water emulsion. Fast-performance liquid chromatography
      analysis indicated that the 45-kDa protein forms a dimer in nondenaturing
      conditions and interacts with the 16- and 31-kDa proteins to form a high
      molecular-mass complex. The 45-kDa protein and the three-protein complex had
      substrate specificities for emulsification and a range of pH activities similar
      to that of alasan. The fact that the purified proteins are active emulsifiers
      should simplify structure-function studies and advance our understanding of their
      biological roles.

PMID- 11229900
TI  - Temperature-driven adaptation of the bacterial community in peat measured by
      using thymidine and leucine incorporation.
AB  - The temperature-driven adaptation of the bacterial community in peat was studied,
      by altering temperature to simulate self-heating and a subsequent return to
      mesophilic conditions. The technique used consisted of extracting the bacterial
      community from peat using homogenization-centrifugation and measuring the rates
      of thymidine (TdR) or leucine (Leu) incorporation by the extracted bacterial
      community at different temperatures. Increasing the peat incubation temperature
      from 25 degrees C to 35, 45, or 55 degrees C resulted in a selection of bacterial
      communities whose optimum temperatures for activity correlated to the peat
      incubation temperatures. Although TdR and Leu incorporations were significantly
      correlated, the Leu/TdR incorporation ratios were affected by temperature. Higher
      Leu/TdR incorporation ratios were found at higher temperatures of incubation of
      the extracted bacterial community. Higher Leu/TdR incorporation ratios were also
      found for bacteria in peat samples incubated at higher temperatures. The
      reappearance of the mesophilic community and disappearance of the thermophilic
      community when the incubation temperature of the peat was shifted down were
      monitored by measuring TdR incorporation at 55 degrees C (thermophilic activity)
      and 25 degrees C (mesophilic activity). Shifting the peat incubation temperature
      from 55 to 25 degrees C resulted in a recovery of the mesophilic activity, with a
      subsequent disappearance of the thermophilic activity. The availability of
      substrate for bacterial growth varied over time and among different peat samples.
      To avoid confounding effects of substrate availability, a temperature adaptation
      index was calculated. This index consisted of the log(10) ratio of TdR
      incorporation at 55 and 25 degrees C. The temperature index decreased linearly
      with time, indicating that no thermophilic activity would be detected by the TdR
      technique 1 month after the temperature downshift. There were no differences
      between the slopes of the temperature adaptation indices over time for peat
      samples incubated at 55 degrees C 3 or 11 days before incubation at 25 degrees C.
      Thus, different levels of bacterial activity did not affect the temperature
      driven adaptation of the bacterial community.

PMID- 11229899
TI  - Genetic diversity among 3-chloroaniline- and aniline-degrading strains of the
      Comamonadaceae.
AB  - We examined the diversity of the plasmids and of the gene tdnQ, involved in the
      oxidative deamination of aniline, in five bacterial strains that are able to
      metabolize both aniline and 3-chloroaniline (3-CA). Three strains have been
      described and identified previously, i.e., Comamonas testosteroni I2 and Delftia
      acidovorans CA28 and BN3.1. Strains LME1 and B8c were isolated in this study from
      linuron-treated soil and from a wastewater treatment plant, respectively, and
      were both identified as D. acidovorans. Both Delftia and Comamonas belong to the
      family Comamonadaceae. All five strains possess a large plasmid of ca. 100 kb,
      but the plasmids from only four strains could be transferred to a recipient
      strain by selection on aniline or 3-CA as a sole source of carbon and/or
      nitrogen. Plasmid transfer experiments and Southern hybridization revealed that
      the plasmid of strain I2 was responsible for total aniline but not 3-CA
      degradation, while the plasmids of strains LME1 and B8c were responsible only for
      the oxidative deamination of aniline. Several transconjugant clones that had
      received the plasmid from strain CA28 showed different degradative capacities:
      all transconjugants could use aniline as a nitrogen source, while only some of
      the transconjugants could deaminate 3-CA. For all four plasmids, the IS1071
      insertion sequence of Tn5271 was found to be located on a 1.4-kb restriction
      fragment, which also hybridized with the tdnQ probe. This result suggests the
      involvement of this insertion sequence element in the dissemination of aniline
      degradation genes in the environment. By use of specific primers for the tdnQ
      gene from Pseudomonas putida UCC22, the diversity of the PCR-amplified fragments
      in the five strains was examined by denaturing gradient gel electrophoresis
      (DGGE). With DGGE, three different clusters of the tdnQ fragment could be
      distinguished. Sequencing data showed that the tdnQ sequences of I2, LME1, B8c,
      and CA28 were very closely related, while the tdnQ sequences of BN3.1 and P.
      putida UCC22 were only about 83% identical to the other sequences. Northern
      hybridization revealed that the tdnQ gene is transcribed only in the presence of
      aniline and not when only 3-CA is present.

PMID- 11229901
TI  - Concentration and detection of cryptosporidium oocysts in surface water samples
      by method 1622 using ultrafiltration and capsule filtration.
AB  - The protozoan parasite Cryptosporidium parvum is known to occur widely in both
      source and drinking water and has caused waterborne outbreaks of gastroenteritis.
      To improve monitoring, the U.S. Environmental Protection Agency developed method
      1622 for isolation and detection of Cryptosporidium oocysts in water. Method 1622
      is performance based and involves filtration, concentration, immunomagnetic
      separation, fluorescent-antibody staining and 4',6-diamidino-2-phenylindole
      (DAPI) counterstaining, and microscopic evaluation. The capsule filter system
      currently recommended for method 1622 was compared to a hollow-fiber ultrafilter
      system for primary concentration of C. parvum oocysts in seeded reagent water and
      untreated surface waters. Samples were otherwise processed according to method
      1622. Rates of C. parvum oocyst recovery from seeded 10-liter volumes of reagent
      water in precision and recovery experiments with filter pairs were 42% (standard
      deviation [SD], 24%) and 46% (SD, 18%) for hollow-fiber ultrafilters and capsule
      filters, respectively. Mean oocyst recovery rates in experiments testing both
      filters on seeded surface water samples were 42% (SD, 27%) and 15% (SD, 12%) for
      hollow-fiber ultrafilters and capsule filters, respectively. Although C. parvum
      oocysts were recovered from surface waters by using the approved filter of method
      1622, the recovery rates were significantly lower and more variable than those
      from reagent grade water. In contrast, the disposable hollow-fiber ultrafilter
      system was compatible with subsequent method 1622 processing steps, and it
      recovered C. parvum oocysts from seeded surface waters with significantly greater
      efficiency and reliability than the filter suggested for use in the version of
      method 1622 tested.

PMID- 11229903
TI  - Behavior of a recombinant baculovirus in lepidopteran hosts with different
      susceptibilities.
AB  - Insect pathogens, such as baculoviruses, that are used as microbial insecticides
      have been genetically modified to increase their speed of action. Nontarget
      species will often be exposed to these pathogens, and it is important to know the
      consequences of infection in hosts across the whole spectrum of susceptibility.
      Two key parameters, speed of kill and pathogen yield, are compared here for two
      baculoviruses, a wild-type Autographa californica nucleopolyhedrovirus (AcNPV),
      AcNPV clone C6, and a genetically modified AcNPV which expresses an insect
      selective toxin, AcNPV-ST3, for two lepidopteran hosts which differ in
      susceptibility. The pathogenicity of the two viruses was equal in the less
      susceptible host, Mamestra brassicae, but the recombinant was more pathogenic
      than the wild-type virus in the susceptible species, Trichoplusia ni. Both
      viruses took longer to kill the larvae of M. brassicae than to kill those of T.
      ni. However, whereas the larvae of T. ni were killed more quickly by the
      recombinant virus, the reverse was found to be true for the larvae of M.
      brassicae. Both viruses produced a greater yield in M. brassicae, and the yield
      of the recombinant was significantly lower than that of the wild type in both
      species. The virus yield increased linearly with the time taken for the insects
      to die. However, despite the more rapid speed of kill of the wild-type AcNPV in
      M. brassicae, the yield was significantly lower for the recombinant virus at any
      given time to death. A lower yield for the recombinant virus could be the result
      of a reduction in replication rate. This was investigated by comparing
      determinations of the virus yield per unit of weight of insect cadaver. The
      response of the two species (to both viruses) was very different: the yield per
      unit of weight decreased over time for M. brassicae but increased for T. ni. The
      implications of these data for risk assessment of wild-type and genetically
      modified baculoviruses are discussed.

PMID- 11229902
TI  - Analysis of the genetic switch and replication region of a P335-type
      bacteriophage with an obligate lytic lifestyle on Lactococcus lactis.
AB  - The DNA sequence of the replication module, part of the lysis module, and
      remnants of a lysogenic module from the lytic P335 species lactococcal
      bacteriophage phi31 was determined, and its regulatory elements were
      investigated. The identification of a characteristic genetic switch including two
      divergent promoters and two cognate repressor genes strongly indicates that phi31
      was derived from a temperate bacteriophage. Regulation of the two early promoters
      was analyzed by primer extension and transcriptional promoter fusions to a lacLM
      reporter. The regulatory behavior of the promoter region differed significantly
      from the genetic responses of temperate Lactococcus lactis phages. The cro gene
      homologue regulates its own production and is an efficient repressor of cI gene
      expression. No detectable cI gene expression could be measured in the presence of
      cro. cI gene expression in the absence of cro exerted minor influences on the
      regulation of the two promoters within the genetic switch. Homology comparisons
      revealed a replication module which is most likely expressed from the promoter
      located upstream of the cro gene homologue. The replication module encoded genes
      with strong homology to helicases and primases found in several Streptococcus
      thermophilus phages. Downstream of the primase homologue, an AT-rich noncoding
      origin region was identified. The characteristics and location of this region and
      its ability to reduce the efficiency of plaquing of phi31 10(6)-fold when present
      at high copy number in trans provide evidence for identification of the phage
      origin of replication. Phage phi31 is an obligately lytic phage that was isolated
      from commercial dairy fermentation environments. Neither a phage attachment site
      nor an integrase gene, required to establish lysogeny, was identified, explaining
      its lytic lifestyle and suggesting its origin from a temperate phage ancestor.
      Several regions showing extensive DNA and protein homologies to different
      temperate phages of Lactococcus, Lactobacillus, and Streptococcus were also
      discovered, indicating the likely exchange of DNA cassettes through horizontal
      gene transfer in the dynamic ecological environment of dairy fermentations.

PMID- 11229904
TI  - Succession of indigenous Pseudomonas spp. and actinomycetes on barley roots
      affected by the antagonistic strain Pseudomonas fluorescens DR54 and the
      fungicide imazalil.
AB  - In recent years, the interest in the use of bacteria for biological control of
      plant-pathogenic fungi has increased. We studied the possible side effects of
      coating barley seeds with the antagonistic strain Pseudomonas fluorescens DR54 or
      a commercial fungicide, imazalil. This was done by monitoring the number of
      indigenous Pseudomonas organisms and actinomycetes on barley roots during growth
      in soil, harvest after 50 days, and subsequent decomposition. Bacteria were
      enumerated by traditional plate spreading on Gould's S1 agar (Pseudomonas) and as
      filamentous colonies on Winogradsky agar (actinomycetes) and by two quantitative
      competitive PCR assays. For this we developed an assay targeting Streptomyces and
      closely related genera. DR54 constituted more than 75% of the Pseudomonas
      population at the root base during the first 21 days but decreased to less than
      10% at day 50. DR54 was not successful in colonizing root tips. Initially, DR54
      affected the number of indigenous Pseudomonas organisms negatively, whereas
      imazalil affected Pseudomonas numbers positively, but the effects were transient.
      Although plate counts were considerably lower than the number of DNA copies, the
      two methods correlated well for Pseudomonas during plant growth, but after plant
      harvest Pseudomonas-specific DNA copy numbers decreased while plate counts were
      in the same magnitude as before. Hence, Pseudomonas was 10-fold more culturable
      in a decomposition environment than in the rhizosphere. The abundance of
      actinomycetes was unaffected by DR54 or imazalil amendments, and CFU and
      quantitative PCR results correlated throughout the experiment. The abundance of
      actinomycetes increased gradually, mostly in numbers of DNA copies, confirming
      their role in colonizing old roots.

PMID- 11229905
TI  - Cryptosporidium parvum infection involving novel genotypes in wildlife from lower
      New York State.
AB  - Cryptosporidium, an enteric parasite of humans and a wide range of other mammals,
      presents numerous challenges to the supply of safe drinking water. We performed a
      wildlife survey, focusing on white-tailed deer and small mammals, to assess
      whether they may serve as environmental sources of Cryptosporidium. A PCR-based
      approach that permitted genetic characterization via sequence analysis was
      applied to wildlife fecal samples (n = 111) collected from September 1996 to July
      1998 from three areas in lower New York State. Southern analysis revealed 22
      fecal samples containing Cryptosporidium small-subunit (SSU) ribosomal DNA; these
      included 10 of 91 white-tailed deer (Odocoileus virginianus) samples, 3 of 5
      chipmunk (Tamias striatus) samples, 1 of 2 white-footed mouse (Peromyscus
      leucopus) samples, 1 of 2 striped skunk (Mephitis mephitis) samples, 1 of 5
      racoon (Procyon lotor) samples, and 6 of 6 muskrat (Ondatra zibethicus) samples.
      All of the 15 SSU PCR products sequenced were characterized as Cryptosporidium
      parvum; two were identical to genotype 2 (bovine), whereas the remainder belonged
      to two novel SSU sequence groups, designated genotypes 3 and 4. Genotype 3
      comprised four deer-derived sequences, whereas genotype 4 included nine sequences
      from deer, mouse, chipmunk, and muskrat samples. PCR analysis was performed on
      the SSU-positive fecal samples for three other Cryptosporidium loci
      (dihydrofolate reductase, polythreonine-rich protein, and beta-tubulin), and 8 of
      10 cloned PCR products were consistent with C. parvum genotype 2. These data
      provide evidence that there is sylvatic transmission of C. parvum involving deer
      and other small mammals. This study affirmed the importance of wildlife as
      potential sources of Cryptosporidium in the catchments of public water supplies.

PMID- 11229906
TI  - Development of a Saccharomyces cerevisiae strain with enhanced resistance to
      phenolic fermentation inhibitors in lignocellulose hydrolysates by heterologous
      expression of laccase.
AB  - To improve production of fuel ethanol from renewable raw materials, laccase from
      the white rot fungus Trametes versicolor was expressed under control of the PGK1
      promoter in Saccharomyces cerevisiae to increase its resistance to phenolic
      inhibitors in lignocellulose hydrolysates. It was found that the laccase activity
      could be enhanced twofold by simultaneous overexpression of the homologous t
      SNARE Sso2p. The factors affecting the level of active laccase obtained, besides
      the cultivation temperature, included pH and aeration. Laccase-expressing and
      Sso2p-overexpressing S. cerevisiae was cultivated in the presence of coniferyl
      aldehyde to examine resistance to lignocellulose-derived phenolic fermentation
      inhibitors. The laccase-producing transformant had the ability to convert
      coniferyl aldehyde at a faster rate than a control transformant not expressing
      laccase, which enabled faster growth and ethanol formation. The laccase-producing
      transformant was also able to ferment a dilute acid spruce hydrolysate at a
      faster rate than the control transformant. A decrease in the content of low
      molecular-mass aromatic compounds, accompanied by an increase in the content of
      high-molecular-mass compounds, was observed during fermentation with the laccase
      expressing strain, illustrating that laccase was active even at the very low
      levels of oxygen supplied. Our results demonstrate the importance of phenolic
      compounds as fermentation inhibitors and the advantage of using laccase
      expressing yeast strains for producing ethanol from lignocellulose.

PMID- 11229907
TI  - Simultaneous measurement of denitrification and nitrogen fixation using isotope
      pairing with membrane inlet mass spectrometry analysis.
AB  - A method for estimating denitrification and nitrogen fixation simultaneously in
      coastal sediments was developed. An isotope-pairing technique was applied to
      dissolved gas measurements with a membrane inlet mass spectrometer (MIMS). The
      relative fluxes of three N(2) gas species ((28)N(2), (29)N(2), and (30)N(2)) were
      monitored during incubation experiments after the addition of (15)NO(3)(-).
      Formulas were developed to estimate the production (denitrification) and
      consumption (N(2) fixation) of N(2) gas from the fluxes of the different isotopic
      forms of N(2). Proportions of the three isotopic forms produced from (15)NO(3)(-)
      and (14)NO(3)(-) agreed with expectations in a sediment slurry incubation
      experiment designed to optimize conditions for denitrification. Nitrogen fixation
      rates from an algal mat measured with intact sediment cores ranged from 32 to 390
      microg-atoms of N m(-2) h(-1). They were enhanced by light and organic matter
      enrichment. In this environment of high nitrogen fixation, low N(2) production
      rates due to denitrification could be separated from high N(2) consumption rates
      due to nitrogen fixation. Denitrification and nitrogen fixation rates were
      estimated in April 2000 on sediments from a Texas sea grass bed (Laguna Madre).
      Denitrification rates (average, 20 microg-atoms of N m(-2) h(-1)) were lower than
      nitrogen fixation rates (average, 60 microg-atoms of N m(-2) h(-1)). The
      developed method benefits from simple and accurate dissolved-gas measurement by
      the MIMS system. By adding the N(2) isotope capability, it was possible to do
      isotope-pairing experiments with the MIMS system.

PMID- 11229908
TI  - Purification, characterization, and overexpression of flavin reductase involved
      in dibenzothiophene desulfurization by Rhodococcus erythropolis D-1.
AB  - The dibenzothiophene (DBT)-desulfurizing bacterium, Rhodococcus erythropolis D-1,
      removes sulfur from DBT to form 2-hydroxybiphenyl using four enzymes, DszC, DszA,
      DszB, and flavin reductase. In this study, we purified and characterized the
      flavin reductase from R. erythropolis D-1 grown in a medium containing DBT as the
      sole source of sulfur. It is conceivable that the enzyme is essential for two
      monooxygenase (DszC and DszA) reactions in vivo. The purified flavin reductase
      contains no chromogenic cofactors and was found to have a molecular mass of 86
      kDa and four identical 22-kDa subunits. The enzyme catalyzed NADH-dependent
      reduction of flavin mononucleotide (FMN), and the K(m) values for NADH and FMN
      were 208 and 10.8 microM, respectively. Flavin adenine dinucleotide was a poor
      substrate, and NADPH was inert. The enzyme did not catalyze reduction of any
      nitroaromatic compound. The optimal temperature and optimal pH for enzyme
      activity were 35 degrees C and 6.0, respectively, and the enzyme retained 30% of
      its activity after heat treatment at 80 degrees C for 30 min. The N-terminal
      amino acid sequence of the purified flavin reductase was identical to that of
      DszD of R. erythropolis IGTS8 (K. A. Gray, O. S. Pogrebinsky, G. T. Mrachko, L.
      Xi, D. J. Monticello, and C. H. Squires, Nat. Biotechnol. 14:1705-1709, 1996).
      The flavin reductase gene was amplified with primers designed by using dszD of R.
      erythropolis IGTS8, and the enzyme was overexpressed in Escherichia coli. The
      specific activity in crude extracts of the overexpressed strain was about 275
      fold that of the wild-type strain.

PMID- 11229909
TI  - Evidence for a genetically stable strain of Campylobacter jejuni.
AB  - The genetic stability of selected epidemiologically linked strains of
      Campylobacter jejuni during outbreak situations was investigated by using
      subtyping techniques. Strains isolated from geographically related chicken flock
      outbreaks in 1998 and from a human outbreak in 1981 were investigated. There was
      little similarity in the strains obtained from the different chicken flock
      outbreaks; however, the strains from each of three chicken outbreaks, including
      strains isolated from various environments, were identical as determined by fla
      typing, amplified fragment length polymorphism (AFLP) analysis, and pulsed-field
      gel electrophoresis, which confirmed the genetic stability of these strains
      during the short time courses of chicken flock outbreaks. The human outbreak
      samples were compared with strain 81116, which originated from the same outbreak
      but has since undergone innumerable laboratory passages. Two main AFLP profiles
      were recognized from this outbreak, which confirmed the serotyping results
      obtained at the time of the outbreak. The major type isolated from this outbreak
      (serotype P6:L6) was exemplified by strain 81116. Despite the long existence of
      strain 81116 as a laboratory strain, the AFLP profile of this strain was
      identical to the profiles of all the other historical P6:L6 strains from the
      outbreak, indicating that the genotype has remained stable for almost 20 years.
      Interestingly, the AFLP profiles of the P6:L6 group of strains from the human
      outbreak and the strains from one of the recent chicken outbreaks were also
      identical. This similarity suggests that some clones of C. jejuni remain
      genetically stable in completely different environments over long periods of time
      and considerable geographical distances.

PMID- 11229910
TI  - Multiple antibiotic resistance (mar) locus in Salmonella enterica serovar
      typhimurium DT104.
AB  - In order to understand the role of the mar locus in Salmonella with regard to
      multiple antibiotic resistance, cyclohexane resistance, and outer membrane
      protein F (OmpF) regulation, a marA::gfp reporter mutant was constructed in an
      antibiotic-sensitive Salmonella enterica serovar Typhimurium DT104 background.
      Salicylate induced marA, whereas a number of antibiotics, disinfectants, and
      various growth conditions did not. Increased antibiotic resistance was observed
      upon salicylate induction, although this was shown to be by both mar-dependent
      and mar-independent pathways. Cyclohexane resistance, however, was induced by
      salicylate by a mar-dependent pathway. Complementation studies with a plasmid
      that constitutively expressed marA confirmed the involvement of mar in Salmonella
      with low-level antibiotic resistance and cyclohexane resistance, although the
      involvement of mar in down regulation of OmpF was unclear. However, marA
      overexpression did increase the expression of a ca. 50-kDa protein, but its
      identity remains to be elucidated. Passage of the marA::gfp reporter mutant with
      increasing levels of tetracycline, a method reported to select for mar mutants in
      Escherichia coli, led to both multiple-antibiotic and cyclohexane resistance.
      Collectively, these data indicate that low-level antibiotic resistance,
      cyclohexane resistance, and modulation of OMPs in Salmonella, as in E. coli, can
      occur in both a mar-dependent and mar-independent manner.

PMID- 11229911
TI  - Acyl-homoserine lactone production is more common among plant-associated
      Pseudomonas spp. than among soilborne Pseudomonas spp.
AB  - A total of 137 soilborne and plant-associated bacterial strains belonging to
      different Pseudomonas species were tested for their ability to synthesize N-acyl
      homoserine lactones (NAHL). Fifty-four strains synthesized NAHL. Interestingly,
      NAHL production appears to be more common among plant-associated than among
      soilborne Pseudomonas spp. Indeed, 40% of the analyzed Pseudomonas syringae
      strains produced NAHL which were identified most often as the short-chain NAHL, N
      hexanoyl-L-homoserine lactone, N-(3-oxo-hexanoyl)-homoserine lactone, and N-(3
      oxo-octanoyl)-L-homoserine lactone (no absolute correlation between genomospecies
      of P. syringae and their ability to produce NAHL could be found). Six strains of
      fluorescent pseudomonads, belonging to the species P. chlororaphis, P.
      fluorescens, and P. putida, isolated from the plant rhizosphere produced
      different types of NAHL. In contrast, none of the strains isolated from soil
      samples were shown to produce NAHL. The gene encoding the NAHL synthase in P.
      syringae pv. maculicola was isolated by complementation of an NAHL-deficient
      Chromobacterium mutant. Sequence analysis revealed the existence of a luxI
      homologue that we named psmI. This gene is sufficient to confer NAHL synthesis
      upon its bacterial host and has strong homology to psyI and ahlI, two genes
      involved in NAHL production in P. syringae pv. tabaci and P. syringae pv.
      syringae, respectively. We identified another open reading frame that we termed
      psmR, transcribed convergently in relation to psmI and partly overlapping psmI;
      this gene encodes a putative LuxR regulatory protein. This gene organization,
      with luxI and luxR homologues facing each other and overlapping, has been found
      so far only in the enteric bacteria Erwinia and Pantoea and in the related
      species P. syringae pv. tabaci.

PMID- 11229912
TI  - Phylogenetic analysis of culturable dimethyl sulfide-producing bacteria from a
      spartina-dominated salt marsh and estuarine water.
AB  - Dimethylsulfoniopropionate (DMSP), an abundant osmoprotectant found in marine
      algae and salt marsh cordgrass, can be metabolized to dimethyl sulfide (DMS) and
      acrylate by microbes having the enzyme DMSP lyase. A suite of DMS-producing
      bacteria isolated from a salt marsh and adjacent estuarine water on DMSP agar
      plates differed markedly from the pelagic strains currently in culture. While
      many of the salt marsh and estuarine isolates produced DMS and methanethiol from
      methionine and dimethyl sulfoxide, none appeared to be capable of producing both
      methanethiol and DMS from DMSP. DMSP, and its degradation products acrylate and
      beta-hydroxypropionate but not methyl-3-mecaptopropionate or 3
      mercaptopropionate, served as a carbon source for the growth of all the alpha-
      and beta- but only some of the gamma-proteobacterium isolates. Phylogenetic
      analysis of 16S rRNA gene sequences showed that all of the isolates were in the
      group Proteobacteria, with most of them belonging to the alpha and gamma
      subclasses. Only one isolate was identified as a beta-proteobacterium, and it had
      >98% 16S rRNA sequence homology with a terrestrial species of Alcaligenes
      faecalis. Although bacterial population analysis based on culturability has its
      limitations, bacteria from the alpha and gamma subclasses of the Proteobacteria
      were the dominant DMS producers isolated from salt marsh sediments and estuaries,
      with the gamma subclass representing 80% of the isolates. The alpha
      proteobacterium isolates were all in the Roseobacter subgroup, while many of the
      gamma-proteobacteria were closely related to the pseudomonads; others were
      phylogenetically related to Marinomonas, Psychrobacter, or Vibrio species. These
      data suggest that DMSP cleavage to DMS and acrylate is a characteristic widely
      distributed among different phylotypes in the salt marsh-estuarine ecosystem.

PMID- 11229913
TI  - Experimental and field studies of Escherichia coli O157:H7 in white-tailed deer.
AB  - Studies were conducted to evaluate fecal shedding of Escherichia coli O157:H7 in
      a small group of inoculated deer, determine the prevalence of the bacterium in
      free-ranging white-tailed deer, and elucidate relationships between E. coli
      O157:H7 in wild deer and domestic cattle at the same site. Six young, white
      tailed deer were orally administered 10(8) CFU of E. coli O157:H7. Inoculated
      deer were shedding E. coli O157:H7 by 1 day postinoculation (DPI) and continued
      to shed decreasing numbers of the bacteria throughout the 26-day trial.
      Horizontal transmission to an uninoculated deer was demonstrated. Although E.
      coli O157:H7 bacteria were recovered from the gastrointestinal tracts of deer
      necropsied from 4 to 26 DPI, attaching and effacing lesions were not apparent in
      any deer. Results are similar to those of inoculation studies in calves and
      sheep. In field studies, E. coli O157 was not detected in 310 fresh deer fecal
      samples collected from the ground. It was detected in feces, but not in meat,
      from 3 of 469 free-ranging deer in 1997. In 1998, E. coli O157 was not detected
      in 140 deer at the single positive site found in 1997; however, it was recovered
      from 13 of 305 dairy and beef cattle at the same location. Isolates of E. coli
      O157:H7 from deer and cattle at this site differed with respect to pulsed-field
      gel electrophoresis patterns and genes encoding Shiga toxins. The low overall
      prevalence of E. coli O157:H7 and the identification of only one site with
      positive deer suggest that wild deer are not a major reservoir of E. coli O157:H7
      in the southeastern United States. However, there may be individual locations
      where deer sporadically harbor the bacterium, and venison should be handled with
      the same precautions recommended for beef, pork, and poultry.

PMID- 11229914
TI  - Factors influencing numbers of Mycobacterium avium, Mycobacterium intracellulare,
      and other Mycobacteria in drinking water distribution systems.
AB  - Eight water distribution systems were sampled over an 18-month period (528 water
      and 55 biofilm samples) to measure the frequency of recovery and number of
      mycobacteria, particularly Mycobacterium avium and Mycobacterium intracellulare,
      in raw source waters before and after treatment and within the distribution
      system. The systems were chosen to assess the influence of source water,
      treatment, and assimilable organic carbon levels on mycobacterial numbers.
      Overall, mycobacterial recovery from the systems was low (15% of samples).
      Numbers of mycobacteria ranged from 10 to 700,000 CFU liter(-1). The number of M.
      avium in raw waters was correlated with turbidity. Water treatment substantially
      reduced the number of mycobacteria in raw waters by 2 to 4 log units.
      Mycobacterial numbers were substantially higher in the distribution system
      samples (average, 25,000-fold) than in those collected immediately downstream
      from the treatment facilities, indicating that mycobacteria grow in the
      distribution system. The increase in mycobacterial numbers was correlated with
      assimilable organic carbon and biodegradable organic carbon levels (r(2) = 0.65,
      P = 0.03). Although M. intracellulare was seldom recovered from water samples, it
      was frequently recovered (six of eight systems) in high numbers from biofilms
      (average, 600 CFU/cm(2)). Evidently, the ecological niches of M. avium and M.
      intracellulare are distinct.

PMID- 11229915
TI  - Expression of six peptidases from Lactobacillus helveticus in Lactococcus lactis.
AB  - For development of novel starter strains with improved proteolytic properties,
      the ability of Lactococcus lactis to produce Lactobacillus helveticus
      aminopeptidase N (PepN), aminopeptidase C (PepC), X-prolyl dipeptidyl
      aminopeptidase (PepX), proline iminopeptidase (PepI), prolinase (PepR), and
      dipeptidase (PepD) was studied by introducing the genes encoding these enzymes
      into L. lactis MG1363 and its derivatives. According to Northern analyses and
      enzyme activity measurements, the L. helveticus aminopeptidase genes pepN, pepC,
      and pepX are expressed under the control of their own promoters in L. lactis. The
      highest expression level, using a low-copy-number vector, was obtained with the
      L. helveticus pepN gene, which resulted in a 25-fold increase in PepN activity
      compared to that of wild-type L. lactis. The L. helveticus pepI gene, residing as
      a third gene in an operon in its host, was expressed in L. lactis under the
      control of the L. helveticus pepX promoter. The genetic background of the L.
      lactis derivatives tested did not affect the expression level of any of the L.
      helveticus peptidases studied. However, the growth medium used affected both the
      recombinant peptidase profiles in transformant strains and the resident peptidase
      activities. The levels of expression of the L. helveticus pepD and pepR clones
      under the control of their own promoters were below the detection limit in L.
      lactis. However, substantial amounts of recombinant pepD and PepR activities were
      obtained in L. lactis when pepD and pepR were expressed under the control of the
      inducible lactococcal nisA promoter at an optimized nisin concentration.

PMID- 11229916
TI  - Rapid screening method for Mycobactericidal activity of chemical germicides that
      uses Mycobacterium terrae expressing a green fluorescent protein gene.
AB  - The slow growth of mycobacteria in conventional culture methods impedes the
      testing of chemicals for mycobactericidal activity. An assay based on expression
      of the green fluorescent protein (GFP) by mycobacteria was developed as a rapid
      alternative. Plasmid pBEN, containing the gene encoding a red-shifted, high
      intensity GFP mutant, was incorporated into Mycobacterium terrae (ATCC 15755),
      and GFP expression was observed by epifluorescence microscopy. Mycobactericidal
      activity was assessed by separately exposing a suspension of M. terrae(pBEN) to
      several dilutions of test germicides based on 7.5% hydrogen peroxide, 2.4%
      alkaline glutaraldehyde, 10% acid glutaraldehyde, and 15.5% of a phenolic agent
      for contact times ranging from 10 to 20 min (22 degrees C), followed by culture
      of the exposed cells in broth (Middlebrook 7H9) and measurement of fluorescence
      every 24 h. When the fluorescence was to be compared with CFU, the samples were
      plated on Middlebrook 7H11 agar and incubated for 4 weeks. No increase in
      fluorescence or CFU occurred in cultures in which the cells had been inactivated
      by the germicide concentrations tested. Where the test bacterium was exposed to
      ineffective levels of the germicides, fluorescence increased after a lag period
      of 1 to 7 days, corresponding to the level of bacterial inactivation. In
      untreated controls, fluorescence increased rapidly to reach a peak in 2 to 4
      days. A good Pearson correlation coefficient (r > or =0.85) was observed between
      the intensity of fluorescence and the number of CFU. The GFP-based fluorescence
      assay reduced the turnaround time in the screening of chemical germicides for
      mycobactericidal activity to < or =7 days.

PMID- 11229917
TI  - Conjugated linoleic acid accumulation via 10-hydroxy-12-octadecaenoic acid during
      microaerobic transformation of linoleic acid by Lactobacillus acidophilus.
AB  - Specific isomers of conjugated linoleic acid (CLA), a fatty acid with potentially
      beneficial physiological and anticarcinogenic effects, were efficiently produced
      from linoleic acid by washed cells of Lactobacillus acidophilus AKU 1137 under
      microaerobic conditions, and the metabolic pathway of CLA production from
      linoleic acid is explained for the first time. The CLA isomers produced were
      identified as cis-9, trans-11- or trans-9, cis-11-octadecadienoic acid and trans
      9, trans-11-octadecadienoic acid. Preceding the production of CLA, hydroxy fatty
      acids identified as 10-hydroxy-cis-12-octadecaenoic acid and 10-hydroxy-trans-12
      octadecaenoic acid had accumulated. The isolated 10-hydroxy-cis-12-octadecaenoic
      acid was transformed into CLA during incubation with washed cells of L.
      acidophilus, suggesting that this hydroxy fatty acid is one of the intermediates
      of CLA production from linoleic acid. The washed cells of L. acidophilus
      producing high levels of CLA were obtained by cultivation in a medium containing
      linoleic acid, indicating that the enzyme system for CLA production is induced by
      linoleic acid. After 4 days of reaction with these washed cells, more than 95% of
      the added linoleic acid (5 mg/ml) was transformed into CLA, and the CLA content
      in total fatty acids recovered exceeded 80% (wt/wt). Almost all of the CLA
      produced was in the cells or was associated with the cells as free fatty acid.

PMID- 11229918
TI  - Identification and cloning of gusA, encoding a new beta-glucuronidase from
      Lactobacillus gasseri ADH.
AB  - The gusA gene, encoding a new beta-glucuronidase enzyme, has been cloned from
      Lactobacillus gasseri ADH. This is the first report of a beta-glucuronidase gene
      cloned from a bacterial source other than Escherichia coli. A plasmid library of
      L. gasseri chromosomal DNA was screened for complementation of an E. coli gus
      mutant. Two overlapping clones that restored beta-glucuronidase activity in the
      mutant strain were sequenced and revealed three complete and two partial open
      reading frames. The largest open reading frame, spanning 1,797 bp, encodes a 597
      amino-acid protein that shows 39% identity to beta-glucuronidase (GusA) of E.
      coli K-12 (EC 3.2.1.31). The other two complete open reading frames, which are
      arranged to be separately transcribed, encode a putative bile salt hydrolase and
      a putative protein of unknown function with similarities to MerR-type regulatory
      proteins. Overexpression of GusA was achieved in a beta-glucuronidase-negative L.
      gasseri strain by expressing the gusA gene, subcloned onto a low-copy-number
      shuttle vector, from the strong Lactobacillus P6 promoter. GusA was also
      expressed in E. coli from a pET expression system. Preliminary characterization
      of the GusA protein from crude cell extracts revealed that the enzyme was active
      across an acidic pH range and a broad temperature range. An analysis of other
      lactobacilli identified beta-glucuronidase activity and gusA homologs in other L.
      gasseri isolates but not in other Lactobacillus species tested.

PMID- 11229919
TI  - pAM401-based shuttle vectors that enable overexpression of promoterless genes and
      one-step purification of tag fusion proteins directly from Enterococcus faecalis.
AB  - Two novel Enterococcus faecalis-Escherichia coli shuttle vectors that utilize the
      promoter and ribosome binding site of bacA on the E. faecalis plasmid pPD1 were
      constructed. The vectors were named pMGS100 and pMGS101. pMGS100 was designed to
      overexpress cloned genes in E. coli and E. faecalis and encodes the bacA promoter
      followed by a cloning site and stop codon. pMGS101 was designed for the
      overexpression and purification of a cloned protein fused to a Strep-tag
      consisting of 9 amino acids at the carboxyl terminus. The Strep-tag provides the
      cloned protein with an affinity to immobilized streptavidin that facilitates
      protein purification. We cloned a promoterless beta-galactosidase gene from E.
      coli and cloned the traA gene of the E. faecalis plasmid pAD1 into the vectors to
      test gene expression and protein purification, respectively. beta-Galactosidase
      was expressed in E. coli and E. faecalis at levels of 10(3) and 10 Miller units,
      respectively. By cloning the pAD1 traA into pMGS101, the protein could be
      purified directly from a crude lysate of E. faecalis or E. coli with an
      immobilized streptavidin matrix by one-step affinity chromatography. The ability
      of TraA to bind DNA was demonstrated by the DNA-associated protein tag affinity
      chromatography method using lysates prepared from both E. coli and E. faecalis
      that overexpress TraA. The results demonstrated the usefulness of the vectors for
      the overexpression and cis/trans analysis of regulatory genes, purification and
      copurification of proteins from E. faecalis, DNA binding analysis, determination
      of translation initiation site, and other applications that require proteins
      purified from E. faecalis.

PMID- 11229920
TI  - Characteristics of a Streptomyces coelicolor A3(2) extracellular protein
      targeting chitin and chitosan.
AB  - Upstream of the Streptomyces coelicolor A3(2) chitinase G gene, a small gene
      (named chb3) is located whose deduced product shares 37% identical amino acids
      with the previously described CHB1 protein from Streptomyces olivaceoviridis. The
      chb3 gene and its upstream region were cloned in a multicopy vector and
      transformed into the plasmid-free Streptomyces lividans TK21 strain. The CHB3
      protein (14.9 kDa) was secreted by the S. lividans TK21 transformant during
      growth in the presence of glucose, N-acetylglucosamine, yeast extract, and
      chitin. The protein was purified to homogeneity using anionic exchange,
      hydrophobic interaction chromatographies, and gel filtration. In contrast to
      CHB1, CHB3 targets alpha-chitin, beta-chitin, and chitosan at pH 6.0 but does so
      relatively loosely. The ecological implications of the divergence of substrate
      specificity of various types of chitin-binding proteins are described.

PMID- 11229921
TI  - Role of dipicolinic acid in survival of Bacillus subtilis spores exposed to
      artificial and solar UV radiation.
AB  - Pyridine-2,6-dicarboxylic acid (dipicolinic acid [DPA]) constitutes approximately
      10% of Bacillus subtilis spore dry weight and has been shown to play a
      significant role in the survival of B. subtilis spores exposed to wet heat and to
      254-nm UV radiation in the laboratory. However, to date, no work has addressed
      the importance of DPA in the survival of spores exposed to environmentally
      relevant solar UV radiation. Air-dried films of spores containing DPA or lacking
      DPA due to a null mutation in the DPA synthetase operon dpaAB were assayed for
      their resistance to UV-C (254 nm), UV-B (290 to 320 nm), full-spectrum sunlight
      (290 to 400 nm), and sunlight from which the UV-B portion was filtered (325 to
      400 nm). In all cases, air-dried DPA-less spores were significantly more UV
      sensitive than their isogenic DPA-containing counterparts. However, the degree of
      difference in UV resistance between the two strains was wavelength dependent,
      being greatest in response to radiation in the UV-B portion of the spectrum. In
      addition, the inactivation responses of DPA-containing and DPA-less spores also
      depended strongly upon whether spores were exposed to UV as air-dried films or in
      aqueous suspension. Spores lacking the gerA, gerB, and gerK nutrient germination
      pathways, and which therefore rely on chemical triggering of germination by the
      calcium chelate of DPA (Ca-DPA), were also more UV sensitive than wild-type
      spores to all wavelengths tested, suggesting that the Ca-DPA-mediated spore
      germination pathway may consist of a UV-sensitive component or components.

PMID- 11229922
TI  - Enhanced iron uptake of Saccharomyces cerevisiae by heterologous expression of a
      tadpole ferritin gene.
AB  - We genetically engineered Saccharomyces cerevisiae to express ferritin, a
      ubiquitous iron storage protein, with the major heavy-chain subunit of tadpole
      ferritin. A 450-kDa ferritin complex can store up to 4,500 iron atoms in its
      central cavity. We cloned the tadpole ferritin heavy-chain gene (TFH) into the
      yeast shuttle vector YEp352 under the control of a hybrid alcohol dehydrogenase
      II and glyceraldehyde-3-phosphate dehydrogenase promoter. We confirmed
      transformation and expression by Northern blot analysis of the recombinant yeast,
      by Western blot analysis using an antibody against Escherichia coli-expressed
      TFH, and with Prussian blue staining that indicated that the yeast-expressed
      tadpole ferritin was assembled into a complex that could bind iron. The
      recombinant yeast was more iron tolerant in that 95% of transformed cells, but
      none of the recipient strain cells, could form colonies on plates containing 30
      mM ferric citrate. The cell-associated concentration of iron was 500 microg per
      gram (dry cell weight) of the recombinant yeast but was 210 microg per gram (dry
      cell weight) in the wild type. These findings indicate that the iron-carrying
      capacity of yeast is improved by heterologous expression of tadpole ferritin and
      suggests that this approach may help relieve dietary iron deficiencies in
      domesticated animals by the use of the engineered yeast as a feed and food
      supplement.

PMID- 11229923
TI  - Spiroplasma symbiont of the pea aphid, Acyrthosiphon pisum (Insecta: Homoptera).
AB  - From a laboratory strain of the pea aphid, Acyrthosiphon pisum, we discovered a
      previously unknown facultative endosymbiotic bacterium. Molecular phylogenetic
      analysis based on 16S ribosomal DNA revealed that the bacterium is a member of
      the genus Spiroplasma. The Spiroplasma organism showed stable vertical
      transmission through successive generations of the host. Injection of hemolymph
      from infected insects into uninfected insects established a stable infection in
      the recipients. The Spiroplasma symbiont exhibited negative effects on growth,
      reproduction, and longevity of the host, particularly in older adults. Of 58
      clonal strains of A. pisum established from natural populations in central Japan,
      4 strains possessed the Spiroplasma organism.

PMID- 11229924
TI  - Specific growth rate plays a critical role in hydrogen peroxide resistance of the
      marine oligotrophic ultramicrobacterium sphingomonas alaskensis strain RB2256.
AB  - The marine oligotrophic ultramicrobacterium Sphingomonas alaskensis RB2256 has a
      physiology that is distinctly different from that of typical copiotrophic marine
      bacteria, such as Vibrio angustum S14. This includes a high level of inherent
      stress resistance and the absence of starvation-induced stress resistance to
      hydrogen peroxide. In addition to periods of starvation in the ocean, slow,
      nutrient-limited growth is likely to be encountered by oligotrophic bacteria for
      substantial periods of time. In this study we examined the effects of growth rate
      on the resistance of S. alaskensis RB2256 to hydrogen peroxide under carbon or
      nitrogen limitation conditions in nutrient-limited chemostats. Glucose-limited
      cultures of S. alaskensis RB2256 at a specific growth rate of 0.02 to 0.13 h(-1)
      exhibited 10,000-fold-greater viability following 60 min of exposure to 25 mM
      hydrogen peroxide than cells growing at a rate of 0.14 h(-1) or higher. Growth
      rate control of stress resistance was found to be specific to carbon and energy
      limitation in this organism. In contrast, V. angustum S14 did not exhibit growth
      rate-dependent stress resistance. The dramatic switch in stress resistance that
      was observed under carbon and energy limitation conditions has not been described
      previously in bacteria and thus may be a characteristic of the oligotrophic
      ultramicrobacterium. Catalase activity varied marginally and did not correlate
      with the growth rate, indicating that hydrogen peroxide breakdown was not the
      primary mechanism of resistance. More than 1,000 spots were resolved on silver
      stained protein gels for cultures growing at rates of 0.026, 0.076, and 0.18 h(
      1). Twelve protein spots had intensities that varied by more than twofold between
      growth rates and hence are likely to be important for growth rate-dependent
      stress resistance. These studies demonstrated the crucial role that nutrient
      limitation plays in the physiology of S. alaskensis RB2256, especially under
      oxidative stress conditions.

PMID- 11229925
TI  - Solid-phase capture of proteins, spores, and bacteria.
AB  - Current methods for the detection of pathogens in food and water samples
      generally require a preenrichment step that allows selective enrichment of the
      test organism. The objective of this research was to eliminate an enrichment step
      to allow detection of bacteria directly in food and water samples in 30 min. A
      high-flow-rate, fluidized bed to capture and concentrate large (bacteria and
      spores) and small (protein) molecules was developed. This format, ImmunoFlow, is
      volume independent and uses large beads (greater than 3 mm in diameter) when
      capturing bacteria to prevent sample clogging when testing food samples.
      Detection of bound targets was done using existing enzyme-linked immunosorbent
      assay (ELISA) protocols. Four antibodies (anti-Escherichia coli O157:H7, 
      Bacillus globigii, -bovine serum albumin [BSA], and -ovalbumin [OVA]) were
      covalently coupled to various glass and ceramic beads. Very small amounts of BSA
      (<1 ng) and OVA (0.2 to 4.0 microg) were detected. Various industrial and
      environmental samples were used to observe the effect of the sample composition
      on the capture of anti-B. globigii and anti-E. coli O157:H7 modified beads. The
      lower limit of detection for both E. coli O157:H7 and B. globigii was 1
      spore/cell independent of the sample size. The activity of anti-B. globigii
      modified beads declined after 3 days. Anti-E. coli O157:H7 modified beads
      declined in their capture ability after 2 days in various storage buffers.
      Storage temperature (4 and 25 degrees C) did not influence the stability. The
      ImmunoFlow technology is capable of capturing bacteria and spores directly from
      samples, with subsequent detection in an ELISA format in 30 min.

PMID- 11229926
TI  - Biological sensor for sucrose availability: relative sensitivities of various
      reporter genes.
AB  - A set of three sucrose-regulated transcriptional fusions was constructed. Fusions
      p61RYTIR, p61RYlac, and p61RYice contain the scrR sucrose repressor gene and the
      promoterless gfp, lacZ, and inaZ reporter genes, respectively, fused to the scrY
      promoter from Salmonella enterica serovar Typhimurium. Cells of Erwinia herbicola
      containing these fusions are induced only in media amended with sucrose,
      fructose, or sorbose. While a large variation in sucrose-dependent reporter gene
      activity was observed in cells harboring all gene fusions, fusions to the inaZ
      reporter gene yielded a much wider range of activity and were responsive to lower
      levels of sucrose than either lacZ or gfp. The lacZ reporter gene was found to be
      more efficient than gfp, requiring approximately 300-fold fewer cells for a
      detectable response over all concentrations of sucrose. Similarly, inaZ was found
      to be more efficient than lacZ, requiring 30-fold fewer cells at 1.45 microM
      sucrose and 6,100-fold fewer cells at 29 mM sucrose for a quantifiable response.
      The fluorescence of individual cells containing p61RYTIR was quantified following
      epifluorescence microscopy in order to relate the fluorescence exhibited by
      populations of cells in batch cultures with that of individual cells in such
      cultures. While the mean fluorescence intensity of a population of individual
      cells increased with increasing concentrations of sucrose, a wide range of
      fluorescence intensity was seen among individual cells. For most cultures the
      distribution of fluorescence intensity among individual cells was log-normally
      distributed, but cells grown in intermediate concentrations of sucrose exhibited
      two distinct populations of cells, one having relatively low fluorescence and
      another with much higher fluorescence. When cells were inoculated onto bean
      leaves, whole-cell ice nucleation and gfp-based biological sensors for sucrose
      each indicated that the average concentration of sucrose on moist leaf surfaces
      was about 20 microM. Importantly, the variation in green fluorescent protein
      fluorescence of biosensor cells on leaves suggested that large spatial variations
      in sugar availability occur on leaves.

PMID- 11229927
TI  - Bacterial populations colonizing and degrading rice straw in anoxic paddy soil.
AB  - Rice straw is a major substrate for the production of methane, a greenhouse gas,
      in flooded rice fields. The bacterial community degrading rice straw under anoxic
      conditions was investigated with molecular methods. Rice straw was incubated in
      paddy soil anaerobically for 71 days. Denaturing gradient gel electrophoresis
      (DGGE) of the amplified bacterial 16S rRNA genes showed that the composition of
      the bacterial community changed during the first 15 days but then was stable
      until the end of incubation. Fifteen DGGE bands with different signal intensities
      were excised, cloned, and sequenced. In addition, DNA was extracted from straw
      incubated for 1 and 29 days and the bacterial 16S rRNA genes were amplified and
      cloned. From these clone libraries 16 clones with different electrophoretic
      mobilities on a DGGE gel were sequenced. From a total of 31 clones, 20 belonged
      to different phylogenetic clusters of the clostridia, i.e., clostridial clusters
      I (14 clones), III (1 clone), IV (1 clone), and XIVa (4 clones). One clone fell
      also within the clostridia but could not be affiliated to one of the clostridial
      clusters. Ten clones grouped closely with the genera Bacillus (3 clones),
      Nitrosospira (1 clone), Fluoribacter (1 clones), and Acidobacterium (2 clones)
      and with clone sequences previously obtained from rice field soil (3 clones). The
      relative abundances of various phylogenetic groups in the rice straw-colonizing
      community were determined by fluorescence in situ hybridization (FISH). Bacteria
      were detached from the incubated rice straw with an efficiency of about 80 to
      90%, as determined by dot blot hybridization of 16S rRNA in extract and residue.
      The number of active (i.e., a sufficient number of ribosomes) Bacteria detected
      with a general eubacterial probe (Eub338) after 8 days of incubation was 61% of
      the total cell counts. This percentage decreased to 17% after 29 days of
      incubation. Most (55%) of the active cells on day 8 belonged to the genus
      Clostridium, mainly to clostridial clusters I (24%), III (6%), and XIVa (24%). An
      additional 5% belonged to the Cytophaga-Flavobacterium cluster of the Cytophaga
      Flavobacterium-Bacteroides phylum, 4% belonged to the alpha, beta, and gamma
      Proteobacteria, and 1.3% belonged to the Bacillus subbranch of the gram-positive
      bacteria with a low G+C content. The results show that the bacterial community
      colonizing and decomposing rice straw developed during the first 15 days of
      incubation and was dominated by members of different clostridial clusters,
      especially clusters I, III, and XIVa.

PMID- 11229928
TI  - Suboxic deposition of ferric iron by bacteria in opposing gradients of Fe(II) and
      oxygen at circumneutral pH.
AB  - The influence of lithotrophic Fe(II)-oxidizing bacteria on patterns of ferric
      oxide deposition in opposing gradients of Fe(II) and O(2) was examined at
      submillimeter resolution by use of an O(2) microelectrode and diffusion
      microprobes for iron. In cultures inoculated with lithotrophic Fe(II)-oxidizing
      bacteria, the majority of Fe(III) deposition occurred below the depth of O(2)
      penetration. In contrast, Fe(III) deposition in abiotic control cultures occurred
      entirely within the aerobic zone. The diffusion microprobes revealed the
      formation of soluble or colloidal Fe(III) compounds during biological Fe(II)
      oxidation. The presence of mobile Fe(III) in diffusion probes from live cultures
      was verified by washing the probes in anoxic water, which removed ca. 70% of the
      Fe(III) content of probes from live cultures but did not alter the Fe(III)
      content of probes from abiotic controls. Measurements of the amount of Fe(III)
      oxide deposited in the medium versus the probes indicated that ca. 90% of the
      Fe(III) deposited in live cultures was formed biologically. Our findings show
      that bacterial Fe(II) oxidation is likely to generate reactive Fe(III) compounds
      that can be immediately available for use as electron acceptors for anaerobic
      respiration and that biological Fe(II) oxidation may thereby promote rapid
      microscale Fe redox cycling at aerobic-anaerobic interfaces.

PMID- 11229929
TI  - Habitat association in two genetic groups of the insect-pathogenic fungus
      metarhizium anisopliae: uncovering cryptic species?
AB  - Strains of insect-pathogenic fungi with high virulence toward certain pest
      insects have great potential for commercial biological control applications.
      Identifying such strains has been a central theme in using fungi for biological
      control. This theme is supported by a persistent paradigm in insect pathology
      which suggests that the host insect is the predominant influence on the
      population genetics of insect-pathogenic fungi. In this study, a population
      genetics analysis of the insect-pathogenic fungus Metarhizium anisopliae from
      forested and agricultural habitats in Ontario, Canada, showed a nonrandom
      association of alleles between two distinct, reproductively isolated groups
      (index of multilocus association = 1.2). Analyses of the mitochondrial DNA showed
      no differences between the groups. The two groups were associated with different
      habitat types, and associations with insect hosts were not found. The group from
      forested areas showed an ability for cold-active growth (i.e., 8 degrees C),
      while the group from the agricultural area showed an ability for growth at high
      temperatures (i.e., 37 degrees C) and resilience to UV exposure. These results
      represent a significant paradigm shift; habitat selection, not host insect
      selection, drives the population structure of these insect-pathogenic
      deuteromycetous fungi. With each group we observed recombining population
      structures as well as clonally reproducing lineages. We discuss whether these
      groups may represent cryptic species. Worldwide, M. anisopliae may be an assembly
      of cryptic species, each adapted to certain environmental conditions. The
      association of fungal genotypes with habitat but not with host insects has
      implications on the criteria for utility of this, and perhaps other, fungal
      biocontrol agents.

PMID- 11229930
TI  - Spatial arrangements and associative behavior of species in an in vitro oral
      biofilm model.
AB  - The spatial arrangements and associative behavior of Actinomyces naeslundii,
      Veillonella dispar, Fusobacterium nucleatum, Streptococcus sobrinus, and
      Streptococcus oralis strains in an in vitro model of supragingival plaque were
      determined. Using species-specific fluorescence-labeled antibodies in conjunction
      with confocal laser scanning microscopy, the volumes and distribution of the five
      strains were assessed during biofilm formation. The volume-derived cell numbers
      of each strain correlated well with respective culture data. Between 15 min and
      64 h, populations of each strain increased in a manner reminiscent of batch
      growth. The microcolony morphologies of all members of the consortium and their
      distributions within the biofilm were characterized, as were interspecies
      associations. Biofilms formed 15 min after inoculation consisted principally of
      single nonaggregated cells. All five strains adhered strongly to the saliva
      conditioned substratum, and therefore, coadhesion played no role during the
      initial phase of biofilm formation. This observation does not reflect the results
      of in vitro coaggregation of the five strains, which depended upon the nature of
      the suspension medium. While the possibility cannot be excluded that some
      interspecies associations observed at later stages of biofilm formation were
      initiated by coadhesion, increase in bacterial numbers appeared to be largely a
      growth phenomenon regulated by the prevailing cultivation conditions.

PMID- 11229931
TI  - Community structure and activity dynamics of nitrifying bacteria in a phosphate
      removing biofilm.
AB  - The microbial community structure and activity dynamics of a phosphate-removing
      biofilm from a sequencing batch biofilm reactor were investigated with special
      focus on the nitrifying community. O(2), NO(2)(-), and NO(3)(-) profiles in the
      biofilm were measured with microsensors at various times during the nonaerated
      aerated reactor cycle. In the aeration period, nitrification was oxygen limited
      and restricted to the first 200 microm at the biofilm surface. Additionally, a
      delayed onset of nitrification after the start of the aeration was observed.
      Nitrate accumulating in the biofilm in this period was denitrified during the
      nonaeration period of the next reactor cycle. Fluorescence in situ hybridization
      (FISH) revealed three distinct ammonia-oxidizing populations, related to the
      Nitrosomonas europaea, Nitrosomonas oligotropha, and Nitrosomonas communis
      lineages. This was confirmed by analysis of the genes coding for 16S rRNA and for
      ammonia monooxygenase (amoA). Based upon these results, a new 16S rRNA-targeted
      oligonucleotide probe specific for the Nitrosomonas oligotropha lineage was
      designed. FISH analysis revealed that the first 100 microm at the biofilm surface
      was dominated by members of the N. europaea and the N. oligotropha lineages, with
      a minor fraction related to N. communis. In deeper biofilm layers, exclusively
      members of the N. oligotropha lineage were found. This separation in space and a
      potential separation of activities in time are suggested as mechanisms that allow
      coexistence of the different ammonia-oxidizing populations. Nitrite-oxidizing
      bacteria belonged exclusively to the genus Nitrospira and could be assigned to a
      16S rRNA sequence cluster also found in other sequencing batch systems.

PMID- 11229932
TI  - Acetate oxidation coupled to Fe(iii) reduction in hyperthermophilic
      microorganisms.
AB  - No hyperthermophilic microorganisms have previously been shown to anaerobically
      oxidize acetate, the key extracellular intermediate in the anaerobic oxidation of
      organic matter. Here we report that two hyperthermophiles, Ferroglobus placidus
      and "Geoglobus ahangari," grow at 85 degrees C by oxidizing acetate to carbon
      dioxide, with Fe(III) serving as the electron acceptor. These results demonstrate
      that acetate could potentially be metabolized within the hot microbial ecosystems
      in which hyperthermophiles predominate, rather than diffusing to cooler
      environments prior to degradation as has been previously proposed.

PMID- 11229933
TI  - Plant-derived oils reduce pathogens and gaseous emissions from stored cattle
      waste.
AB  - Carvacrol and thymol in combination at 6.7 mM each completely inhibited the
      production of short-chain volatile fatty acids and lactate from cattle waste in
      anoxic flasks over 23 days. Fecal coliforms were reduced from 4.6 x 10(6) to 2.0
      x 10(3) cells per ml 2 days after treatment and were nondetectable within 4 days.
      Total anaerobic bacteria were reduced from 8.4 x 10(10) to 1.5 x 10(7) cells per
      ml after 2 days and continued to be suppressed to that level after 14 days. If
      the concentration of carvacrol or thymol were doubled (13.3 mM), either could be
      used to obtain the same inhibitory fermentation effect. We conclude that
      carvacrol or thymol may be useful as an antimicrobial chemical to control
      pathogens and odor in stored livestock waste.

PMID- 11229934
TI  - Oligophilic bacteria as tools to monitor aseptic pharmaceutical production units.
AB  - The bacterial loads of air, surfaces, and personnel in clean rooms are routinely
      monitored using a set of standard media. Bacteria that can grow on these media
      are a tiny fraction of the total numbers in any environment. A substantial
      proportion of bacteria long thought to be unculturable were recently shown to be
      oligophilic. Oligophile counts in clean rooms in our studies exceeded the
      standard plate counts by up to 2 orders of magnitude. They responded to
      disinfection routines in ways similar to the responses of conventional bacteria.
      We suggest that oligophiles are better tools than conventional bacteria for
      environmental monitoring in aseptic pharmaceutical production units.

PMID- 11229935
TI  - Factors affecting catalase expression in Pseudomonas aeruginosa biofilms and
      planktonic cells.
AB  - Previous work with Pseudomonas aeruginosa showed that catalase activity in
      biofilms was significantly reduced relative to that in planktonic cells. To
      better understand biofilm physiology, we examined possible explanations for the
      differential expression of catalase in cells cultured in these two different
      conditions. For maximal catalase activity, biofilm cells required significantly
      more iron (25 microM as FeCl(3)) in the medium, whereas planktonic cultures
      required no addition of iron. However, iron-stimulated catalase activity in
      biofilms was still only about one-third that in planktonic cells. Oxygen effects
      on catalase activity were also investigated. Nitrate-respiring planktonic
      cultures produced approximately twice as much catalase activity as aerobic
      cultures grown in the presence of nitrate; the nitrate stimulation effect could
      also be demonstrated in biofilms. Cultures fermenting arginine had reduced
      catalase levels; however, catalase repression was also observed in aerobic
      cultures grown in the presence of arginine. It was concluded that iron
      availability, but not oxygen availability, is a major factor affecting catalase
      expression in biofilms.

PMID- 11229936
TI  - Dual role of GdmH in producer immunity and secretion of the Staphylococcal
      lantibiotics gallidermin and epidermin.
AB  - The biosynthetic gene clusters of the staphylococcal lantibiotics epidermin and
      gallidermin are distinguished by the presence of the unique genes epiH and gdmH,
      respectively. They encode accessory factors for the ATP-binding cassette
      transporters that mediate secretion of the antimicrobial peptides. Here, we show
      that gdmH also contributes to immunity to gallidermin but not to nisin. gdmH
      alone affected susceptibility to gallidermin only moderately, but it led to a
      multiplication of the immunity level mediated by the FEG immunity genes when
      cloned together with the gdmT gene, suggesting a synergistic activity of the H
      and FEG systems. gdmH-related genes were identified in the genomes of several
      bacteria, indicating an involvement in further cellular functions.

PMID- 11229937
TI  - Determination of virus abundance in marine sediments.
AB  - In this study, we optimized procedures to enumerate viruses from marine sediments
      by epifluorescence microscopy using SYBR Green I as a stain. The highest virus
      yields from the bulk of the sediments were obtained by utilizing pyrophosphate
      and 3 min of sonication. The efficiency of extraction benthic viruses by
      pyrophosphate-ultrasound treatment was about 60% of the extractable virus
      particles. Samples treated with nucleases had increased virus counts, suggesting
      a masking effect of extracellular DNA. No significant differences were observed
      between virus counts obtained by epifluorescence microscopy and transmission
      electron microscopy. Both formaldehyde and glutaraldehyde gave significant
      reductions of virus counts after only 24 h of sediment storage, but no further
      loss occurred after 7 days.

PMID- 11229938
TI  - Substrate selectivity of a 3-nitrophenol-induced metabolic system in Pseudomonas
      putida 2NP8 transforming nitroaromatic compounds into ammonia under aerobic
      conditions.
AB  - The 3-nitrophenol-induced enzyme system in cells of Pseudomonas putida 2NP8
      manifested a wide substrate range in transforming nitroaromatic compounds through
      to ammonia production. All of the 30 mono- or dinitroaromatic substrates except 4
      nitrophenol, 2,4-dinitrophenol, 2,4,6-trinitrophenol, 3-nitroaniline, 2
      nitrobenzoic acid, and 2-nitrofuran were quickly transformed. Ammonia production
      from most nitroaromatic substrates appeared to be stoichiometric.

PMID- 11229940
TI  - Reductive, coenzyme A-mediated pathway for 3-chlorobenzoate degradation in the
      phototrophic bacterium Rhodopseudomonas palustris.
AB  - We isolated a strain of Rhodopseudomonas palustris (RCB100) by selective
      enrichment in light on 3-chlorobenzoate to investigate the steps that it uses to
      accomplish anaerobic dechlorination. Analyses of metabolite pools as well as
      enzyme assays suggest that R. palustris grows on 3-chlorobenzoate by (i)
      converting it to 3-chlorobenzoyl coenzyme A (3-chlorobenzoyl-CoA), (ii)
      reductively dehalogenating 3-chlorobenzoyl-CoA to benzoyl-CoA, and (iii)
      degrading benzoyl-CoA to acetyl-CoA and carbon dioxide. R. palustris uses 3
      chlorobenzoate only as a carbon source and thus incorporates the acetyl-CoA that
      is produced into cell material. The reductive dechlorination route used by R.
      palustris for 3-chlorobenzoate degradation differs from those previously
      described in that a CoA thioester, rather than an unmodified aromatic acid, is
      the substrate for complete dehalogenation.

PMID- 11229942
TI  - Cocaine, ethanol, and cocaethylene cardiotoxity in an animal model of cocaine and
      ethanol abuse.
AB  - OBJECTIVES: Simultaneous abuse of cocaine and ethanol affects 12 million
      Americans annually. In combination, these substances are substantially more toxic
      than either drug alone. Their combined cardiac toxicity may be due to independent
      effects of each drug; however, they may also be due to cocaethylene (CE), a
      cocaine metabolite formed only in the presence of ethanol. The purpose of this
      study was to delineate the role of CE in the combined cardiotoxicity of cocaine
      and ethanol in a model simulating their abuse. METHODS: Twenty-three dogs were
      randomized to receive either 1) three intravenous (IV) boluses of cocaine 7.5
      mg/kg with ethanol (1 g/kg) as an IV infusion (C+E, n = 8), 2) three cocaine
      boluses only (C, n = 6), 3) ethanol infusion only (E, n = 5), or 4) placebo
      boluses and infusion (n = 4). Hemodynamic measurements, electrocardiograms, and
      serum drug concentrations were obtained at baseline, and then at fixed time
      intervals after each drug was administered. RESULTS: Two of eight dogs in the C+E
      group experienced cardiovascular collapse. The most dramatic hemodynamic changes
      occurred after each cocaine bolus in the C+E and C only groups; however,
      persistent hemodynamic changes occurred in the C+E group. Peak CE levels were
      associated with a 45% (SD +/- 22%, 95% CI = 22% to 69%) decrease in cardiac
      output (p < 0.05), a 56% (SD +/- 23%, 95% CI = 32% to 80%) decrease in dP/dt(max)
      (p <.006), and a 23% (SD +/- 15%, 95% CI = 7% to 49%) decrease in SVO(2) (p <
      0.025). Ventricular arrhythmias were primarily observed in the C+E group, in
      which four of eight dogs experienced ventricular tachycardia. CONCLUSIONS:
      Cocaine and ethanol in combination were more toxic than either substance alone.
      Co-administration resulted in prolonged cardiac toxicity and was dysrhythmogenic.
      Peak serum cocaethylene concentrations were associated with prolonged myocardial
      depression.

PMID- 11229941
TI  - Genetic evidence that loss of virulence associated with gacS or gacA mutations in
      Pseudomonas syringae B728a does not result from effects on alginate production.
AB  - Mutations in the global regulatory genes gacS and gacA render Pseudomonas
      syringae pv. syringae strain B728a completely nonpathogenic in foliar
      infiltration assays on bean plants. It had been previously demonstrated that gac
      genes regulate alginate production in Pseudomonas species, while other published
      work indicated that alginate is involved in the pathogenic interaction of P.
      syringae on bean plants. Together, these results suggested that the effects of
      gacS and gacA mutations on virulence in B728a might stem directly from a role in
      regulating alginate. In this report, we confirm a role for gac genes in both algD
      expression and alginate production in B728a. However, B728a mutants completely
      devoid of detectable alginate were as virulent as the wild-type strain in our
      assay. Thus, factors other than, or in addition to, a deficiency of alginate must
      be involved in the lack of pathogenicity observed with gacS and gacA mutants.

PMID- 11229939
TI  - Recovery and analysis of formyltetrahydrofolate synthetase gene sequences from
      natural populations of acetogenic bacteria.
AB  - Primers for PCR amplification of partial (1,102 of 1,680 bp)
      formyltetrahydrofolate synthetase (FTHFS) gene sequences were developed and
      tested. Partial FTHFS sequences were successfully amplified from DNA from pure
      cultures of known acetogens, from other FTHFS-producing organisms, from the roots
      of the smooth cordgrass, Spartina alterniflora, and from fresh horse manure. The
      amplimers recovered were cloned, their nucleotide sequences were determined, and
      their translated amino acid sequences were used to construct phylogenetic trees.
      We found that FTHFS sequences from homoacetogens formed a monophyletic cluster
      that did not contain sequences from nonhomoacetogens and that FTHFS sequences
      appear to be informative regarding major physiological features of FTHFS
      producing organisms.

PMID- 11229943
TI  - LET versus EMLA for pretreating lacerations: a randomized trial.
AB  - OBJECTIVE: To compare the anesthetic efficacy of EMLA cream (eutectic mixture of
      local anesthetics) with that of LET solution (lidocaine, epinephrine, tetracaine)
      for pretreating lacerations prior to lidocaine injection. METHODS: This was a
      randomized, double-blind clinical trial in a convenience sample of 60 patients
      aged 1 to 59 years with traumatic lacerations. Eligible wounds were
      uncomplicated, clean lacerations < or = 6 hours old. Finger and toe lacerations
      were excluded. At the time of initial presentation to triage, patients were
      randomized to LET or EMLA. A nurse applied the topical anesthetic into the
      laceration with a 5-mL syringe. A physician assessed the laceration edges for the
      presence of blanching and adequacy of anesthesia to a 27-gauge needlestick.
      Supplemental lidocaine was then infiltrated through the wound edges and the pain
      of infiltration was recorded by the patient (or guardian) on a 100-mm visual
      analog scale marked "most pain" at the high end. A sample of 44 patients had 90%
      power to detect a 20-mm difference in injection pain (two-tailed alpha = 0.05).
      RESULTS: Sixty patients were randomized to LET (29) or EMLA (31). Median age was
      8.5 years; 23% were female. Most lacerations were facial and closed with sutures.
      There was no difference in baseline characteristics between groups. More wounds
      treated with LET were anesthetic to a needlestick than wounds treated with EMLA
      (73% vs 40%, p = 0.01); however, there was no between-group difference in the
      median pain of lidocaine infiltration (LET-12 mm vs EMLA-13 mm, p = 0.89).
      CONCLUSIONS: Pretreatment of simple lacerations with LET or EMLA at the time of
      patient presentation results in similar amounts of pain of subsequent local
      infiltration of lidocaine

PMID- 11229944
TI  - Short-term outcome of seizure patients who refuse transport after out-of-hospital
      evaluation.
AB  - OBJECTIVE: To determine the short-term outcome of patients with a known seizure
      disorder who have a seizure, are evaluated by out-of-hospital care providers, and
      refuse transport. METHODS: This was a prospective study conducted over a 15-month
      period. Philadelphia Fire Department paramedics contacted a medical command
      physician whenever they encountered a patient with a known seizure disorder who
      had had another seizure and was refusing transport. After confirming that the
      patient had the mental capacity to refuse care and understood the associated
      risks, the physician recorded the patient's name, address, and telephone number.
      Beginning three days later, a registered nurse attempted to reach the patient by
      telephone and administer a brief questionnaire about his or her medical outcome.
      Patients not reached by telephone were sent a certified letter. The names of
      patients lost to follow-up were compared with medical examiner records to confirm
      that they had not died during the follow-up period. RESULTS: Of 63 patients
      enrolled in the study, 52 (82.5%) were reached in follow-up. Of these, three
      (5.8%) had another seizure within 72 hours and recontacted 911. One of these
      patients (1.9%) was hospitalized. Twenty (38.5%) patients contacted their primary
      care physicians. There were no deaths, including patients lost to follow-up.
      CONCLUSIONS: Most patients (94.2%) who were evaluated by out-of-hospital care
      providers for a seizure and refused transport had no further seizure activity in
      the subsequent 72 hours. However, because there is a risk of recurrence, out-of
      hospital care providers and medical command physicians should ensure that
      patients understand the risks of refusal.

PMID- 11229945
TI  - Role of flexion-extension radiographs in blunt pediatric cervical spine injury.
AB  - OBJECTIVE: To determine whether flexion-extension cervical spine radiography
      (FECSR) is abnormal in children who have sustained blunt cervical spine injury
      (CSI) when standard cervical spine radiography (SCSR) demonstrates no acute
      abnormalities. METHODS: This was a blinded radiographic review of 129 patients <
      or = 16 years of age evaluated at an academic pediatric trauma center during July
      1990-March 1996. All patients had SCSR (anteroposterior/lateral views) and FECSR
      performed for a trauma-related event within seven days of injury. RESULTS: Of 46
      patients without acute abnormalities on SCSR, one patient (with final clinical
      diagnosis of "no CSI") had acute abnormalities on FECSR (95% CI = 0.06% to
      11.5%). Of 50 patients with isolated loss of lordosis on SCSR, no patient had
      acute abnormalities on FECSR (95% CI = 0% to 5.8%). The FECSR review revealed no
      acute abnormalities in 75 of 83 patients (90.4%) with suspicious findings for CSI
      viewed on SCSR (95% CI = 81.9% to 95.7%). Complications during FECSR were noted
      in one patient with transient paresthesias (0.8%) (95% CI = 0.02% to 4.2%).
      CONCLUSIONS: In children who underwent acute radiographic evaluation of blunt
      cervical spine trauma, FECSR was unlikely to be abnormal when no acute
      abnormality or isolated loss of lordosis was evident on SCSR. In a subset of
      patients with suspicious findings for occult CSI on SCSR, FECSR was useful in
      ruling out ligamentous instability in the acute, posttrauma setting.

PMID- 11229947
TI  - The emergency medicine subinternship--a standard experience for medical students?
AB  - OBJECTIVE: To determine whether emergency medicine (EM)-bound and non-EM-bound
      senior medical students on the EM subinternship have a uniform experience with
      respect to number and acuity of patients seen and procedures performed. METHODS:
      Prospective observational analysis of patient diagnosis and procedures recorded
      in logs by students at a public teaching hospital over 12 consecutive months.
      Logs were reviewed blindly and assigned an acuity level based on predetermined
      criteria. Preselected procedures were categorized as general or surgical and
      tallied. Identity, specialty choice, gender, and month of rotation for each
      student were identified. RESULTS: Seventy of 74 students completed logs. On
      average, 34 EM-bound students saw 59.82 patients (95% CI = 55.19 to 64.45) and
      performed 10.58 procedures (95% CI = 8.62 to 12.56); 36 non-EM-bound students saw
      51.17 patients (95% CI = 47.41 to 54.90) and performed 8.33 procedures (95% CI =
      6.81 to 9.84). Univariate analysis showed EM-bound students saw more patients
      than non-EM-bound students, performed more surgical procedures, and saw higher
      acuity patients (p = 0.004; 0.009; 0.016). Multivariate analyses controlled for
      EM specialty, gender, and month. Significant effects for EM specialty were found
      (ordinary least squares) for number of patients, procedures, and surgical
      procedures (p = 0.013; 0.048; 0.011). Logistic regression explaining acuity level
      showed EM specialty and gender were significant (p = 0.010; 0.038). CONCLUSIONS:
      In an EM subinternship, experience was variable between EM-bound and non-EM-bound
      students. Male students saw lower-acuity patients. The EM-bound students saw more
      patients, higher-acuity patients, and performed more procedures than non-EM-bound
      cohorts. Emergency medicine educators responsible for medical education should be
      aware of these differences.

PMID- 11229946
TI  - Modifying a standard industry clinical trial consent form improves patient
      information retention as part of the informed consent process.
AB  - OBJECTIVE: Informed consent is a required part of clinical research. Industry
      consent forms may be complex and difficult to understand. A comparison was
      performed between a standard, industry consent form (IF) and a modified,
      shortened version of the same form (MF) to determine which allows the patient to
      retain more information in the immediate postconsent period. METHODS: This was a
      prospective, randomized study performed in an urban, county teaching emergency
      department (ED). A convenience sample (based on the availability of one of two
      research assistants being present in the ED) of 100 patients with a history of
      asthma seen in the ED were enrolled. After reading the consent form, 50 MF and 50
      IF patients were given a postconsent test to determine how much information was
      retained. Mean differences in test scores between the IF and MF were determined.
      RESULTS: The population had a mean age (+/-SD) of 39.4 +/- 12.1 years (range 18
      80); 52% were female. The overall score for the study population was 9.6 (+/
      2.0), range 2-12 (maximum 12). The MF score was 10.6 (+/-1.4) vs the IF score of
      8.6 (+/-2.1); mean difference = 2.0 (95% CI = 1.3 to 2.7, p < 0.0001). The MF
      group had significantly more correct answers than the IF group with the following
      questions (MF%, IF%; mean difference in proportions with 95% CIs): purpose (96,
      70; 26, 95% CI = 12 to 40); randomization (78, 44; 34, 95% CI = 16 to 52); study
      duration (94, 70; 24, 95% CI = 10 to 38); risks (92, 74; 18, 95% CI = 4 to 32);
      benefits (94, 78; 16, 95% CI = 3 to 29); alternative treatments (88, 70; 18, 95%
      CI = 2 to 34); confidentiality (98, 88; 10, 95% CI = 0.2 to 20); and voluntary
      participation (74, 54; 20, 95% CI = 2 to 38). Adverse event compensation had the
      poorest correct rate (54, 38; 13, 95% CI = -6 to 32). Subsequently, after taking
      the postconsent test, 98% wrote that they read the entire MF, while only 68%
      wrote that they read the entire IF (mean difference in proportions 30%, 95% CI =
      17% to 43%). CONCLUSIONS: Compared with an industry consent form, a shortened
      version, focusing on Food and Drug Administration and Department of Health and
      Human Services informed consent guidelines, allowed patients to retain more
      information in the immediate postconsent period.

PMID- 11229948
TI  - Effect of ethnicity on denial of authorization for emergency department care by
      managed care gatekeepers.
AB  - OBJECTIVE: After a pilot study suggested that African American patients enrolled
      in managed care organizations (MCOs) were more likely than whites to be denied
      authorization for emergency department (ED) care through gatekeeping, the authors
      sought to determine the association between ethnicity and denial of authorization
      in a second, larger study at another hospital. METHODS: A retrospective cohort
      design was used, with adjustment for triage score, age, gender, day and time of
      arrival at the ED, and type of MCO. RESULTS: African Americans were more likely
      to be denied authorization for ED visits by the gatekeepers representing their
      MCOs even after adjusting for confounders, with an odds ratio of 1.52 (95% CI =
      1.18 to 1.94). CONCLUSIONS: African Americans were more likely than whites to be
      denied authorization for ED visits. The observational study design raises the
      possibility that incomplete control of confounding contributed to or accounted
      for the association between ethnicity and gatekeeping decisions. Nevertheless,
      the questions that these findings raise about equity of gatekeeping indicate a
      need for additional research in this area.

PMID- 11229950
TI  - Taking care of our patients.

PMID- 11229949
TI  - Emergency department utilization by noninstitutionalized elders.
AB  - OBJECTIVES: To the best of the authors' knowledge, no nationally representative,
      population-based study has characterized the proportion of elders using the
      emergency department (ED) and factors associated with ED use by elders. This
      article describes the proportion of elder Medicare beneficiaries using the ED and
      identifies attributes associated with elder ED users as compared with nonusers.
      METHODS: The 1993 Medicare Current Beneficiary Survey was used, a national,
      population-based, cross-sectional survey of Medicare beneficiaries linked with
      Medicare claims data. The study population was limited to 9,784
      noninstitutionalized individuals aged 66 years or older. The Andersen model of
      health service utilization was used, which explains variation in ED use through a
      combination of predisposing (demographic and social), enabling (access to care),
      and need (comorbidity and health status) characteristics. RESULTS: Eighteen
      percent of the sample used the ED at least once during 1993. Univariate analysis
      showed ED users were older; were less educated and lived alone; had lower income
      and higher Charlson Comorbidity Index scores; and were less satisfied with their
      ability to access care than nonusers (p < 0.01, chi-square). Logistic regression
      identified older age, less education, living alone, higher comorbidity scores,
      worse reported health, and increased difficulties with activities of daily living
      as factors associated with ED use (p < 0.05). Need characteristics predicted ED
      use with the greatest accuracy. CONCLUSIONS: The proportion of elder ED users is
      slightly higher than previously reported among Medicare beneficiaries. Need
      (comorbidity and health status) characteristics predict ED utilization with the
      greatest accuracy.

PMID- 11229951
TI  - Does the reference really support that assertion? The potential for citing
      research reports out of context.

PMID- 11229952
TI  - Ethics seminars: Consent and refusal in an urban American emergency department:
      two case studies.
AB  - Patients in the emergency department frequently voice refusals of care or are
      unable or unwilling to consent to care. While general principles surrounding
      consent and refusal can be articulated in theory, it is often far more
      complicated in the real setting. Further, it is impossible to contemplate in
      advance every possible situation that might arise. In order to properly care for
      patients, the emergency physician has an obligation to understand ethical
      principles and the reasoning process one must go through to resolve an ethical
      dilemma. Emergency physicians face such complex decisions on a routine basis.
      Ethical reasoning skills are obviously a core competence in emergency medicine,
      even if easy answers are elusive. Two cases are presented that illustrate this
      complexity, and routes to resolution are discussed.

PMID- 11229953
TI  - Emergency determination of decision-making capacity: balancing autonomy and
      beneficence in the emergency department.
AB  - The determination of decision-making capacity (DMC) is an essential component of
      securing voluntary informed consent, for either treatment or refusal of care.
      Decision-making capacity should be determined on some level during each patient
      encounter. Decision-making capacity includes the ability to receive, process, and
      understand information, the ability to deliberate, the ability to make choices,
      and the ability to communicate those preferences. For patients in whom DMC may be
      uncertain, a more explicit approach to determination of DMC is recommended.
      However, DMC determination must neither compromise patient safety nor delay
      needed care. When DMC determination is challenging, or when the ramifications of
      a decision are serious, the assistance of a third party (such as a surrogate, a
      consultant, or another clinician) may be valuable in discerning the most
      appropriate action. In addition to the obvious clinical utility of DMC
      assessment, the steps taken in the very establishment of DMC may promote patient
      trust, professionalism, and humanistic clinical practice. While DMC may be
      conditional, the compassion and respect we have for our patients must be
      unconditional.

PMID- 11229954
TI  - Magnetically guided orotracheal intubation.
AB  - OBJECTIVE: To describe a novel endotracheal intubation technique, magnetically
      guided intubation (MGI), and its rate of success in inexperienced medical
      students and interns using an airway mannequin model. METHODS: This was a
      prospective, descriptive study of 25 medical students and interns participating
      in an introductory course on emergency medicine without prior experience in human
      orotracheal intubation. Magnetically guided intubation consists of a strong
      external magnet placed over the cricothyroid membrane to guide the introduction
      of a standard endotracheal tube containing a stylet with a magnetized tip. An
      airway mannequin was placed in a rigid cervical spinal collar to increase the
      difficulty of the intubation, and each student performed two sequential
      intubation attempts using MGI. The proportions of successful intubations and the
      time to complete intubation were determined. Descriptive statistics were used to
      describe point estimates and 95% confidence intervals for means and proportions
      of continuous and categorical data, respectively. RESULTS: Of 25 participants, 19
      were students and six were interns. Their mean age was 27 years, and 76% were
      male. The overall proportion of successful intubations using MGI was 80% (95% CI
      = 69% to 91%). Of 24 intubations, 48% were attempted without visualization of the
      vocal cords; 67% were successful (95% CI = 46% to 87%). The mean time required to
      complete intubation was 17.0 seconds (95% CI = 14.5 to 19.5 seconds).
      CONCLUSIONS: A novel method of orotracheal intubation using magnetic guidance is
      described as achieving a high rate of successful intubations when performed by
      inexperienced intubators.

PMID- 11229955
TI  - Routine carbon monoxide screening by emergency medical technicians.
AB  - Residential carbon monoxide (CO) poisoning represents a significant cause of
      unintentional morbidity and mortality in the United States. Screening by fire
      departments and utility companies is usually limited to instances in which there
      are symptoms of CO poisoning or there is activation of a home CO detector.
      OBJECTIVES: To determine whether emergency medical services (EMS) personnel can
      perform routine CO screening during 911 calls. METHODS: A prospective
      observational study was conducted in an urban EMS system using emergency medical
      technicians (EMTs) to screen for elevated CO levels during emergency responses.
      The EMTs carried hand-held CO meters that detect as little as one part per
      million of CO. Readings were taken at the patient's side during indoor patient
      contacts. If time allowed, a brief questionnaire was then administered to
      patients or by-standers concerning knowledge about CO poisoning, type of
      household heating system, and presence of home CO detectors. RESULTS: In a three
      month convenience sample of emergency responses, there were 264 residential CO
      readings obtained. There were nine (3.4%) positive residential readings, all with
      chief complaints believed to be unrelated to CO toxicity. Two hundred twelve
      surveys were completed during these emergency responses, with 145 of 212 (68%)
      participants familiar with the term "carbon monoxide poisoning." Only 54 of 145
      (37%) participants could name any signs or symptoms of CO poisoning. Of those
      surveyed, 133 of 212 (63%) participants reported an oil- or gas-powered heating
      system in their residence. Carbon monoxide detectors were absent in 185 of 212
      (87%) residences, including all domiciles in which a positive CO reading was
      obtained. CONCLUSIONS: Emergency medical services personnel can perform routine
      CO screening and detect occult elevations in CO levels during 911 responses.
      Public knowledge of CO poisoning is limited and the use of home CO detectors is
      rare in this study population.

PMID- 11229956
TI  - Ability of patients to accurately recall the severity of acute painful events.
AB  - OBJECTIVE: Pain studies require prospective patient enrollment to ensure accurate
      pain assessment. The authors correlated pain assessments of an acute painful
      episode over a one-week period and determined the accuracy of patient pain
      severity recall over time. METHODS: This was a prospective, descriptive,
      longitudinal study. Participants were a convenience sample of 50 emergency
      department patients with acute pain resulting from injuries or painful invasive
      procedures. A trained research assistant administered a structured pain survey
      containing demographic and historical features to all patients. Patients
      sequentially assessed their pain severity using a vertical 100-mm visual analog
      scale marked "most pain" at the top, a verbal numeric rating scale ranging from 0
      to 100 from none to worst (NRS100), and a verbal numeric rating scale ranging
      from 0 to 10 from none to worst (NRS10). Patients were contacted by phone and
      asked to reassess their initial pain severity one and seven days later using the
      two verbal numeric rating scales. Analysis of pain assessments using the various
      scales at the three time intervals was performed with Pearson's and Spearman's
      coefficients and repeated-measures analysis of variance (ANOVA). RESULTS: There
      were 50 patients with a mean age of 41 years. Correlation between initial pain
      assessments on the three scales ranged from 0.83 to 0.92. Correlations between
      the initial and 24-hour assessments were NRS100-0.98 and NRS10-0.98. Correlations
      between the initial and one-week assessments were NRS100-0.96 and NRS10-0.97.
      Repeated-measures ANOVA showed no significant change in pain assessments over
      time for both verbal numeric scales. CONCLUSIONS: Pain severity assessments of
      acute painful events one and seven days later were similar and highly correlated
      with initial assessments using both verbal numeric scales. Patients accurately
      recall the severity of an acute painful episode for at least one week after its
      occurrence, which may allow retrospective pain assessments.

PMID- 11229957
TI  - Concussive convulsions: emergency department assessment and management of a
      frequently misunderstood entity.
AB  - Immediate concussive convulsions are an unusual but dramatic sequela to head
      injuries. Previously believed to be an epileptic phenomenon, they are now thought
      to be a brief traumatic functional decerebration that results from loss of
      cortical inhibition. With concussive convulsions generally occurring within
      seconds of head impact and lasting up to several minutes, patients are initially
      in a tonic phase, followed by a clonic convulsion. A postictal phase is generally
      brief if it occurs at all with these episodes. Patients with isolated concussive
      convulsions have no evidence of structural brain injury as assessed with
      neuroimaging studies or physical examination. Neuropsychological testing often
      demonstrates transient cortical dysfunction consistent with the concussive
      episode. The long-term outcome for patients with isolated concussive convulsion
      is universally good, with no long-term neurologic sequelae and no increased
      incidence of early or late posttraumatic epilepsy. Emergency department
      management should focus on evaluation of the associated concussive injury. The
      concussive convulsion requires no specific therapy, and antiepileptic medication
      is not indicated.

PMID- 11229958
TI  - Bilevel positive airway pressure for presumed pulmonary edema.

PMID- 11229959
TI  - Patch4 the flowing dam.

PMID- 11229960
TI  - Wide-complex tachycardia: diagnostic value of the Brugada algorithm in emergency
      medicine.

PMID- 11229966
TI  - NKF-K/DOQI Clinical Practice Guidelines: Update 2000. Foreword.

PMID- 11229967
TI  - I. NKF-K/DOQI Clinical Practice Guidelines for Hemodialysis Adequacy: update
      2000.

PMID- 11229968
TI  - II. NKF-K/DOQI Clinical Practice Guidelines for Peritoneal Dialysis Adequacy:
      update 2000.

PMID- 11229969
TI  - III. NKF-K/DOQI Clinical Practice Guidelines for Vascular Access: update 2000.

PMID- 11229970
TI  - IV. NKF-K/DOQI Clinical Practice Guidelines for Anemia of Chronic Kidney Disease:
      update 2000.

PMID- 11229971
TI  - Drug addiction: to the cortex.and beyond!

PMID- 11229972
TI  - The dream in contemporary psychiatry.
AB  - OBJECTIVE: This article offers selective reviews of cogent sectors of research
      regarding the dream in contemporary psychiatry. METHOD: First, the author
      discusses relatively recent research (1953-1999) on the neurobiology and clinical
      psychophysiology of dreaming sleep; second, he reviews experimental cognitive
      neuroscientific studies of perception, emotion, and memory and the putative
      interrelationships among them in generating dream imagery; and third, he
      interprets psychoanalytic studies (1900-1999) on related aspects of dreams and
      the dream process. RESULTS: Exploration for interrelationships among information
      from these three areas entails discussion of the mind/brain problem. These
      considerations illuminate some of the logical and interpretive dilemmas that
      enter into debates about Freud's theory of the dream. CONCLUSIONS: The author
      proposes a preliminary psychobiologic concept of the dream process and discusses,
      in light of the foregoing considerations, the importance of collaborative
      research for developing a realistic perspective concerning the proper place of
      the dream in contemporary psychiatry.

PMID- 11229973
TI  - Does fast dissociation from the dopamine d(2) receptor explain the action of
      atypical antipsychotics?: A new hypothesis.
AB  - OBJECTIVE: Although atypical antipsychotics are becoming the treatment of choice
      for schizophrenia, what makes an antipsychotic "atypical" is not clear. This
      article provides a new hypothesis about the mechanism of action of atypical
      antipsychotics. METHOD: Published data regarding the molecular, animal model,
      neuroimaging, and clinical aspects of typical and atypical antipsychotics were
      reviewed to develop this hypothesis. Particular attention was paid to data
      regarding the role of the serotonin 5-HT(2) and dopamine D(4) receptors in
      atypicality. RESULTS: Neuroimaging data show that optimal dopamine D(2) occupancy
      is sufficient to produce the atypical antipsychotic effect. Freedom from motor
      side effects results from low D(2) occupancy, not from high 5-HT(2) occupancy. If
      D(2) occupancy is excessive, atypicality is lost even in the presence of high 5
      HT(2) occupancy. Animal data show that a rapid dissociation from the D(2)
      receptor at a molecular level produces the atypical antipsychotic effect. In
      vitro data show that the single most powerful predictor of atypicality for the
      current generation of atypical antipsychotics is fast dissociation from the D(2)
      receptor, not its high affinity at 5-HT(2), D(4), or another receptor.
      CONCLUSIONS: The authors propose that fast dissociation from the D(2) receptor
      makes an antipsychotic more accommodating of physiological dopamine transmission,
      permitting an antipsychotic effect without motor side effects, prolactin
      elevation, or secondary negative symptoms. In contrast to the multireceptor
      hypotheses, the authors predict that the atypical antipsychotic effect can be
      produced by appropriate modulation of the D(2) receptor alone; the blockade of
      other receptors is neither necessary nor sufficient.

PMID- 11229974
TI  - The human genome sequence: the human genome I: chromosomes and protein coding.

PMID- 11229975
TI  - Treatment of chronic depression with a 12-week program of interpersonal
      psychotherapy.

PMID- 11229977
TI  - Association of dopamine transporter reduction with psychomotor impairment in
      methamphetamine abusers.
AB  - OBJECTIVE: Methamphetamine is a popular and highly addictive drug of abuse that
      has raised concerns because it has been shown in laboratory animals to be
      neurotoxic to dopamine terminals. The authors evaluated if similar changes occur
      in humans and assessed if they were functionally significant. METHOD: Positron
      emission tomography scans following administration of [(11)C]d-threo
      methylphenidate (a dopamine transporter ligand) measured dopamine transporter
      levels (a marker of dopamine cell terminals) in the brains of 15 detoxified
      methamphetamine abusers and 18 comparison subjects. Neuropsychological tests were
      also performed to assess motor and cognitive function. RESULTS: Methamphetamine
      abusers showed significant dopamine transporter reduction in the striatum (mean
      differences of 27.8% in the caudate and 21.1% in the putamen) relative to the
      comparison subjects; this reduction was evident even in abusers who had been
      detoxified for at least 11 months. Dopamine transporter reduction was associated
      with motor slowing and memory impairment. CONCLUSIONS: These results provide
      evidence that methamphetamine at dose levels taken by human abusers of the drug
      leads to dopamine transporter reduction that is associated with motor and
      cognitive impairment. These results emphasize the urgency of alerting clinicians
      and the public of the long-term changes that methamphetamine can induce in the
      human brain.

PMID- 11229978
TI  - Higher cortical and lower subcortical metabolism in detoxified methamphetamine
      abusers.
AB  - OBJECTIVE: Methamphetamine has raised concerns because it may be neurotoxic to
      the human brain. Although prior work has focused primarily on the effects of
      methamphetamine on dopamine cells, there is evidence that other neuronal types
      are affected. The authors measured regional brain glucose metabolism, which
      serves as a marker of brain function, to assess if there is evidence of
      functional changes in methamphetamine abusers in regions other than those
      innervated by dopamine cells. METHOD: Fifteen detoxified methamphetamine abusers
      and 21 comparison subjects underwent positron emission tomography following
      administration of [(18)F]fluorodeoxyglucose. RESULTS: Whole brain metabolism in
      the methamphetamine abusers was 14% higher than that of comparison subjects; the
      differences were most accentuated in the parietal cortex (20%). After
      normalization for whole brain metabolism, methamphetamine abusers exhibited
      significantly lower metabolism in the thalamus (17% difference) and striatum
      (where the differences were larger for the caudate [12%] than for the putamen
      [6%]). Statistical parametric mapping analyses corroborated these findings,
      revealing higher metabolism in the parietal cortex and lower metabolism in the
      thalamus and striatum of methamphetamine abusers. CONCLUSIONS: The fact that the
      parietal cortex is a region devoid of any significant dopaminergic innervation
      suggests that the higher metabolism seen in this region in the methamphetamine
      abusers is the result of methamphetamine effects in circuits other than those
      modulated by dopamine. In addition, the lower metabolism in the striatum and
      thalamus (major outputs of dopamine signals into the cortex) is likely to reflect
      the functional consequence of methamphetamine in dopaminergic circuits. These
      results provide evidence that, in humans, methamphetamine abuse results in
      changes in function of dopamine- and nondopamine-innervated brain regions.

PMID- 11229979
TI  - Limbic responsiveness to procaine in cocaine-addicted subjects.
AB  - OBJECTIVE: The limbic system plays a critical role in motivation, emotional
      expression, and memory. The authors investigated whether a state of permanent
      limbic neuronal hyperexcitability, or sensitization, is present in cocaine
      addicts as a consequence of repeated cocaine use. METHOD: Single photon emission
      computed tomography (SPECT) of regional cerebral blood flow (rCBF) was used to
      compare the central nervous system response to the limbic stimulus procaine in 10
      cocaine-dependent male patients and 10 healthy comparison male subjects. RESULTS:
      The cocaine-addicted subjects demonstrated bilateral activation of the
      orbitofrontal cortex after the procaine challenge, whereas the comparison
      subjects showed activation of the anterior cingulate, bilateral insular, and
      right amygdalar regions. After receiving placebo, the cocaine-addicted subjects
      showed markedly lower rCBF in the bilateral orbitofrontal cortex than the
      comparison subjects. CONCLUSIONS: The pattern of hypoperfusion in the placebo
      state followed by heightened activation with procaine in the cocaine-addicted
      subjects is similar to the pattern of interictal hypoperfusion and ictal
      hyperperfusion that has been observed in subjects with epilepsy. The findings for
      the cocaine-addicted subjects may thus represent evidence of localized
      (orbitofrontal) sensitization.

PMID- 11229981
TI  - Anterior cingulate activity as a predictor of degree of treatment response in
      major depression: evidence from brain electrical tomography analysis.
AB  - OBJECTIVE: The anterior cingulate cortex has been implicated in depression.
      Results are best interpreted by considering anatomic and cytoarchitectonic
      subdivisions. Evidence suggests depression is characterized by hypoactivity in
      the dorsal anterior cingulate, whereas hyperactivity in the rostral anterior
      cingulate is associated with good response to treatment. The authors tested the
      hypothesis that activity in the rostral anterior cingulate during the depressed
      state has prognostic value for the degree of eventual response to treatment.
      Whereas prior studies used hemodynamic imaging, this investigation used EEG.
      METHOD: The authors recorded 28-channel EEG data for 18 unmedicated patients with
      major depression and 18 matched comparison subjects. Clinical outcome was
      assessed after nortriptyline treatment. Of the 18 depressed patients, 16 were
      considered responders 4-6 months after initial assessment. A median split was
      used to classify response, and the pretreatment EEG data of patients showing
      better (N=9) and worse (N=9) responses were analyzed with low-resolution
      electromagnetic tomography, a new method to compute three-dimensional cortical
      current density for given EEG frequency bands according to a Talairach brain
      atlas. RESULTS: The patients with better responses showed hyperactivity (higher
      theta activity) in the rostral anterior cingulate (Brodmann's area 24/32). Follow
      up analyses demonstrated the specificity of this finding, which was not
      confounded by age or pretreatment depression severity. CONCLUSIONS: These
      results, based on electrophysiological imaging, not only support hemodynamic
      findings implicating activation of the anterior cingulate as a predictor of
      response in depression, but they also suggest that differential activity in the
      rostral anterior cingulate is associated with gradations of response.

PMID- 11229980
TI  - Insomnia, self-medication, and relapse to alcoholism.
AB  - OBJECTIVE: This study was an investigation of the frequencies of insomnia and its
      self-medication with alcohol in a group of alcoholic patients, as well as the
      relationship of these variables to alcoholic relapse. METHOD: The subjects were
      172 men and women receiving treatment for alcohol dependence. They completed a
      sleep questionnaire, measures of alcohol problem severity and depression
      severity, and polysomnography after at least 2 weeks of abstinence. RESULTS: On
      the basis of eight items from the Sleep Disorders Questionnaire, 61% of the
      subjects were classified as having symptomatic insomnia during the 6 months
      before treatment entry. Compared to patients without insomnia, patients with
      insomnia were more likely to report frequent alcohol use for sleep (55% versus
      28%), had significantly worse polysomnographic measures of sleep continuity, and
      had more severe alcohol dependence and depression. Among 74 alcoholics who were
      followed a mean of 5 months after treatment, 60% with baseline insomnia versus
      30% without baseline insomnia relapsed to any use of alcohol, a significant
      difference. Insomnia remained a robust predictor of relapse after application of
      logistic regression analysis to control for other variables. A history of self
      medicating insomnia with alcohol did not significantly predict subsequent
      relapse. CONCLUSIONS: The majority of alcoholic patients entering treatment
      reported insomnia symptoms. Given the potential link between insomnia and
      relapse, routine questions about sleep in clinical and research settings are
      warranted.

PMID- 11229982
TI  - Depression and self-reported functional status in older primary care patients.
AB  - OBJECTIVE: The authors' goal was to examine whether depression is associated with
      overreporting of functional disability. METHOD: The subjects were 304 patients 60
      years old or older who were recruited from primary care settings. Measures
      included examiner ratings of depression diagnosis and medical burden and self
      reported and examiner-rated functional assessments. Multiple regression
      techniques were used to determine the independent association of depression with
      self-reported function after examiner-rated function was added to the analysis as
      a covariate. RESULTS: Depression diagnosis was associated with poorer self
      reported role functioning, whether the patient attributed the disability to
      physical or emotional causes. Depression was not independently associated with
      poorer self-reported physical functioning. CONCLUSIONS: Clinicians and
      researchers should recognize that depression can confound the self-reporting and
      attribution of functional disability.

PMID- 11229983
TI  - Axis I psychiatric comorbidity and its relationship to historical illness
      variables in 288 patients with bipolar disorder.
AB  - OBJECTIVE: Bipolar disorder often co-occurs with other axis I disorders, but
      little is known about the relationships between the clinical features of bipolar
      illness and these comorbid conditions. Therefore, the authors assessed comorbid
      lifetime and current axis I disorders in 288 patients with bipolar disorder and
      the relationships of these comorbid disorders to selected demographic and
      historical illness variables. METHOD: They evaluated 288 outpatients with bipolar
      I or II disorder, using structured diagnostic interviews and clinician
      administered and self-rated questionnaires to determine the diagnosis of bipolar
      disorder, comorbid axis I disorder diagnoses, and demographic and historical
      illness characteristics. RESULTS: One hundred eighty-seven (65%) of the patients
      with bipolar disorder also met DSM-IV criteria for at least one comorbid lifetime
      axis I disorder. More patients had comorbid anxiety disorders (N=78, 42%) and
      substance use disorders (N=78, 42%) than had eating disorders (N=9, 5%). There
      were no differences in comorbidity between patients with bipolar I and bipolar II
      disorder. Both lifetime axis I comorbidity and current axis I comorbidity were
      associated with earlier age at onset of affective symptoms and syndromal bipolar
      disorder. Current axis I comorbidity was associated with a history of development
      of both cycle acceleration and more severe episodes over time. CONCLUSIONS:
      Patients with bipolar disorder often have comorbid anxiety, substance use, and,
      to a lesser extent, eating disorders. Moreover, axis I comorbidity, especially
      current comorbidity, may be associated with an earlier age at onset and worsening
      course of bipolar illness. Further research into the prognostic and treatment
      response implications of axis I comorbidity in bipolar disorder is important and
      is in progress.

PMID- 11229984
TI  - Are suicide attempters who self-mutilate a unique population?
AB  - OBJECTIVE: Individuals who mutilate themselves are at greater risk for suicidal
      behavior. Clinically, however, there is a perception that the suicide attempts of
      self-mutilators are motivated by the desire for attention rather than by a
      genuine wish to die. The purpose of this study was to determine differences
      between suicide attempters with and without a history of self-mutilation. METHOD:
      The authors examined demographic characteristics, psychopathology, objective and
      perceived lethality of suicide attempts, and perceptions of their suicidal
      behavior in 30 suicide attempters with cluster B personality disorders who had a
      history of self-mutilation and a matched group of 23 suicide attempters with
      cluster B personality disorders who had no history of self-mutilation. RESULTS:
      The two groups did not differ in the objective lethality of their attempts, but
      their perceptions of the attempts differed. Self-mutilators perceived their
      suicide attempts as less lethal, with a greater likelihood of rescue and with
      less certainty of death. In addition, suicide attempters with a history of self
      mutilation had significantly higher levels of depression, hopelessness,
      aggression, anxiety, impulsivity, and suicide ideation. They exhibited more
      behaviors consistent with borderline personality disorder and were more likely to
      have a history of childhood abuse. Self-mutilators had more persistent suicide
      ideation, and their pattern for suicide was similar to their pattern for self
      mutilation, which was characterized by chronic urges to injure themselves.
      CONCLUSIONS: Suicide attempters with cluster B personality disorders who have a
      history of self-mutilation tend to be more depressed, anxious, and impulsive, and
      they also tend to underestimate the lethality of their suicide attempts.
      Therefore, clinicians may be unintentionally misled in assessing the suicide risk
      of self-mutilators as less serious than it is.

PMID- 11229985
TI  - Life satisfaction and suicide: a 20-year follow-up study.
AB  - OBJECTIVE: The authors investigated whether self-reported life satisfaction
      predicted suicide over a period of 20 years (1976-1995) in adults unselected for
      mental health status. METHOD: A nationwide sample of adults aged 18-64 years
      (N=29,173) from the Finnish Twin Cohort responded to a health questionnaire that
      included a life satisfaction scale (score range=4-20, with higher scores
      indicating greater dissatisfaction) that covered four items: interest in life,
      happiness, general ease of living, and feeling of loneliness. "Dissatisfied"
      subjects (life satisfaction score=12-20) were compared to "satisfied" subjects
      (score=4-6). Mortality data were derived from the national registry and analyzed
      with Cox regression. RESULTS: Dissatisfaction at baseline (life satisfaction
      score=12-20) was associated with a higher risk of suicide throughout the 20-year
      follow-up period (age-adjusted hazard ratio=3.02, 95% confidence interval
      [CI]=1.83-4.98). The association was somewhat stronger in the first decade
      (hazard ratio=4.46, 95% CI=1.95-10.20) than in the second (hazard ratio=2.34, 95%
      CI=1.24-4.45). A dose-response relationship was also found. Men with the highest
      degrees of dissatisfaction (life satisfaction score=19-20) were 24.85 times as
      prone to commit suicide as satisfied men during the first 10 years of the follow
      up period. Throughout the entire follow-up, life dissatisfaction still predicted
      suicide after adjusting for age, sex, baseline health status, alcohol
      consumption, smoking status, and physical activity (hazard ratio=1.74, 95%
      CI=1.02-2.97). Subjects who reported dissatisfaction at baseline and again 6
      years later showed a high suicide risk (hazard ratio=6.84, 95% CI=1.99-23.50)
      compared to those who repeatedly reported satisfaction. CONCLUSIONS: Life
      dissatisfaction has a long-term effect on the risk of suicide, and this seems to
      be partly mediated through poor health behavior. Life satisfaction seems to be a
      composite health indicator.

PMID- 11229986
TI  - Traumatic brain injury and schizophrenia in members of schizophrenia and bipolar
      disorder pedigrees.
AB  - OBJECTIVE: Schizophrenia following a traumatic brain injury could be a phenocopy
      of genetic schizophrenia or the consequence of a gene-environment interaction.
      Alternatively, traumatic brain injury and schizophrenia could be spuriously
      associated if those who are predisposed to develop schizophrenia have greater
      amounts of trauma for other reasons. The authors investigated the relationship
      between traumatic brain injury and psychiatric diagnoses in a large group of
      subjects from families with at least two biologically related first-degree
      relatives with schizophrenia, schizoaffective disorder, or bipolar disorder.
      METHOD: The Diagnostic Interview for Genetic Studies was used to determine
      history of traumatic brain injury and diagnosis for 1,275 members of multiplex
      bipolar disorder pedigrees and 565 members of multiplex schizophrenia pedigrees.
      RESULTS: Rates of traumatic brain injury were significantly higher for those with
      a diagnosis of schizophrenia, bipolar disorder, and depression than for those
      with no mental illness. However, multivariate analysis of within-pedigree data
      showed that mental illness was related to traumatic brain injury only in the
      schizophrenia pedigrees. Independent of diagnoses, family members of those with
      schizophrenia were more likely to have had traumatic brain injury than were
      members of the bipolar disorder pedigrees. The members of the schizophrenia
      pedigrees also failed to show the gender difference for traumatic brain injury
      (more common in men than in women) that was expected and was present in the
      bipolar disorder pedigrees. Subjects with a schizophrenia diagnosis who were
      members of the bipolar disorder pedigrees (and thus had less genetic
      vulnerability to schizophrenia) were less likely to have had traumatic brain
      injury (4.5%) than were subjects with schizophrenia who were members of the
      schizophrenia pedigrees (and who had greater genetic vulnerability to
      schizophrenia) (19.6%). CONCLUSIONS: Members of the schizophrenia pedigrees, even
      those without a schizophrenia diagnosis, had greater exposure to traumatic brain
      injury compared to members of the bipolar disorder pedigrees. Within the
      schizophrenia pedigrees, traumatic brain injury was associated with a greater
      risk of schizophrenia, consistent with synergistic effects between genetic
      vulnerability for schizophrenia and traumatic brain injury. Posttraumatic-brain
      injury schizophrenia in multiplex schizophrenia pedigrees does not appear to be a
      phenocopy of the genetic disorder.

PMID- 11229987
TI  - Velocardiofacial syndrome: are structural changes in the temporal and mesial
      temporal regions related to schizophrenia?
AB  - OBJECTIVE: Velocardiofacial syndrome results from a microdeletion on chromosome
      22 (22q11.2). Clinical studies indicate that more than 30% of children with the
      syndrome will develop schizophrenia. The authors sought to determine whether
      neuroanatomical features in velocardiofacial syndrome are similar to those
      reported in the literature on schizophrenia by measuring the volumes of the
      temporal lobe, superior temporal gyrus, and mesial temporal structures in
      children and adolescents with velocardiofacial syndrome. METHOD: Twenty-three
      children and adolescents with velocardiofacial syndrome and 23 comparison
      subjects, individually matched for age and gender, received brain magnetic
      resonance imaging (MRI) scans. Analysis of covariance models were used to compare
      regional brain volumes. Correlations between residualized brain volumes and age
      were standardized and compared with the Fisher r-to-z transformation. RESULTS:
      Children with velocardiofacial syndrome had significantly smaller average
      temporal lobe, superior temporal gyrus, and hippocampal volumes than normal
      comparison children, although these differences were commensurate with a lower
      overall brain size in the affected children. In a cross-sectional analysis,
      children with velocardiofacial syndrome exhibited aberrant volumetric reductions
      with age that were localized to the temporal lobe and left hippocampal regions.
      CONCLUSIONS: Abnormal temporal lobe and hippocampal development in
      velocardiofacial syndrome is potentially concordant with MRI findings in the
      schizophrenia literature. Temporal lobe and mesial temporal structures may
      represent a shared substrate for the effects of the 22q11.2 deletion and for the
      complex etiological pathways that lead to schizophrenia. Longitudinal research
      may help determine which children with velocardiofacial syndrome are at risk for
      serious psychiatric illness in adulthood.

PMID- 11229988
TI  - Defective recognition of one's own actions in patients with schizophrenia.
AB  - OBJECTIVE: The possibility that delusions of influence could be related to
      abnormal recognition of one's own actions was investigated in persons with
      schizophrenia. METHOD: Schizophrenic patients with (N=6) and without (N=18)
      delusions of influence were compared with normal subjects (N=29) on an action
      recognition task. The image of a virtual right hand holding a joystick was
      presented to the subjects through a mirror so that the image was superimposed on
      their real hand holding a real joystick. Subjects executed discrete movements in
      different directions. Angular biases and temporal delays were randomly introduced
      in some trials, such that the movement of the virtual hand departed from the
      movement executed by the subjects. After each trial, subjects were asked whether
      the movement they saw was their own. RESULTS: Compared with normal subjects, both
      patient groups made significantly more recognition errors in trials with temporal
      delays. In trials with angular biases, the error rate of patients with delusions
      of influence significantly differed from that of comparison subjects and from
      that of patients without delusions of influence. CONCLUSIONS: The findings
      support the hypothesis that delusions of influence are associated with a
      quantifiable difficulty in correct self-attribution of actions. This difficulty
      may be related to a specific impairment of a neural action attribution system.

PMID- 11229989
TI  - A comparison of three scales for assessing social functioning in primary care.
AB  - OBJECTIVE: Assessment of functional status is increasingly important in clinical
      trials and outcome research. Although several scales for assessing functioning
      are widely used, they vary in coverage, and direct comparisons among them are
      rare. Comparative information is useful in guiding selection of appropriate
      scales for research applications. METHOD: Results from three scales that measure
      functioning-the Medical Outcomes Study 36-item Short-Form Health Survey, the
      Social Adjustment Scale Self-Report, and the Social Adaptation Self-Evaluation
      Scale-were compared in a consecutively selected sample of 211 patients coming to
      primary care. Patients also received psychiatric assessments. RESULTS: All three
      scales were acceptable to patients, showed few significant correlations with
      demographic variables, and were able to differentiate psychiatrically ill and
      well patients. Correlations among scales, even among scale items that assessed
      similar domains of functioning, were modest. CONCLUSIONS: Although all three
      scales are presumed to assess functional status, their item content and coverage
      differ. Selection of a scale requires a review of the scale items and
      consideration of research priorities and the characteristics of the study group.
      If functional status is a critical outcome measure, use of more than one scale
      may be necessary.

PMID- 11229990
TI  - The response evaluation measure (REM-71): a new instrument for the measurement of
      defenses in adults and adolescents.
AB  - OBJECTIVE: There is widespread agreement that the concept of defense is useful,
      but large-scale studies with representative cohorts are lacking. Self-report
      measures capturing conscious derivatives of defense can facilitate such studies.
      The authors report the design and initial performance of a new self-report
      measure of specific defenses. METHOD: A 71-item questionnaire based on a
      developmental model of defenses was created, pilot tested, and refined. The item
      pool was given to two independent clinical researchers for the classification of
      items (concordance=98.5%). The instrument was then administered to 1,875
      nonclinical subjects drawn from two suburban high schools and from a public
      waiting area of a local airport (1,038 female subjects; mean age=21.0 years,
      SD=11.9, range=13-89), who were also assessed with a simple screening measure
      covering demographic variables and satisfaction with life. RESULTS: The internal
      consistency of the questionnaire items was good. Two factors emerged from a
      factor analysis of the items, paralleling Vaillant's theoretical model. Most
      defenses made unique, significant contributions to these factors. Defenses and
      factors related in the expected direction with scores on life satisfaction in
      various domains. CONCLUSIONS: The Response Evaluation Measure is a brief,
      coherent, and potentially useful screening instrument for the assessment of
      defenses in adults and adolescents.

PMID- 11229991
TI  - Psychiatrists disciplined by a state medical board.
AB  - OBJECTIVE: This study determined the risk of discipline by a medical board for
      psychiatrists relative to other physicians and assessed the contributions to such
      risk. METHOD: Physicians disciplined by the California Medical Board in a 30
      month period were compared with matched groups of nondisciplined physicians.
      RESULTS: Among 584 disciplined physicians, there were 75 (12.8%) psychiatrists,
      nearly twice the number of psychiatrists among nondisciplined physicians. Female
      psychiatrists were underrepresented in the disciplined group. Psychiatrists were
      significantly more likely than nonpsychiatrist physicians to be disciplined for
      sexual relationships with patients and about as likely to be charged with
      negligence or incompetence. The disciplined and nondisciplined psychiatrists did
      not differ significantly from a group of 75 nondisciplined psychiatrists on years
      since medical school graduation, international medical graduate status, or board
      certification. The disciplined group included significantly more psychiatrists
      who claimed child psychiatry as their first or second specialty and significantly
      fewer psychoanalysts. CONCLUSIONS: Organized psychiatry has an obligation to
      address sexual contact with patients and other causes for medical board
      discipline. This obligation may be addressable through enhanced residency
      training, recertification exams, and other means of education.

PMID- 11229993
TI  - Hallucinogens on the Internet: a vast new source of underground drug information.
AB  - OBJECTIVE: The illicit use of hallucinogens is reemerging in the United States,
      especially among well-educated adults and teenagers. These same groups are also
      frequent users of the Internet. The authors sought to characterize the extent of
      information about hallucinogens available to Internet users. METHOD: Using
      standard Internet search techniques, the authors located 81 hallucinogen-related
      sites and categorized the information provided. RESULTS: Internet sites offer
      thousands of pages of information-albeit of questionable accuracy-on how to
      obtain, synthesize, extract, identify, and ingest hallucinogens. Much of this
      information has yet to appear in textbooks. By contrast, the authors found few
      U.S. government agency sites offering cautionary material about hallucinogen use.
      CONCLUSIONS: Using the Internet, potential hallucinogen users can bypass
      traditional channels of medical information and learn in great detail how to
      obtain and use numerous drugs with unknown hazards.

PMID- 11229992
TI  - Perceived stigma as a predictor of treatment discontinuation in young and older
      outpatients with depression.
AB  - OBJECTIVE: The authors' goal was to examine the extent to which perceived stigma
      affected treatment discontinuation in young and older adults with major
      depression. METHOD: A two-stage sampling design identified 92 new admissions of
      outpatients with major depression. Perceived stigma was assessed at admission.
      Discontinuation of treatment was recorded at 3-month follow-up. RESULTS: Although
      younger patients reported perceiving more stigma than older patients, stigma
      predicted treatment discontinuation only among the older patients. CONCLUSIONS:
      Patients' perceptions of stigma at the start of treatment influence their
      subsequent treatment behavior. Stigma is an appropriate target for intervention
      aimed at improving treatment adherence and outcomes.

PMID- 11229994
TI  - Suppression of cellular immunity in men with a past history of posttraumatic
      stress disorder.
AB  - OBJECTIVE: High rates of medical morbidity have been reported in subjects with
      posttraumatic stress disorder (PTSD). The authors examined immune function in
      subjects in remission from past PTSD. METHOD: The initial study group was
      composed of 1,550 Japanese male workers. Japanese versions of the Events Check
      List, the Impact of Event Scale-Revised, and the Diagnostic Interview Schedule
      for DSM-IV were used to identify subjects who had a past history of PTSD. Twelve
      of the workers were identified as having such a history. These men were matched
      in age and smoking habits, which affect immunity, to 48 comparison subjects who
      had similar stressful life experiences but no current or past history of PTSD.
      Natural killer (NK) cell activity, lymphocyte subset counts, and production of
      interferon gamma (IFN-gamma) and interleukin-4 (IL-4) were measured in the 60 men
      by means of phytohemagglutinin stimulation. RESULTS: The number of lymphocytes,
      number of T cells, NK cell activity, and total amounts of IFN-gamma and IL-4 were
      significantly lower in the 12 men with a past history of PTSD. CONCLUSIONS: PTSD
      leaves a long-lasting immunosuppression and has long-term implications for
      health.

PMID- 11229995
TI  - Quantitative morphology of the caudate and putamen in patients with cocaine
      dependence.
AB  - OBJECTIVE: Deficits in dopaminergic function may contribute to hypertrophy of
      striatal structures associated with typical neuroleptic treatment. In light of a
      body of research that has associated chronic cocaine use with extrapyramidal
      symptoms and striatal dopaminergic depletion, the authors looked for evidence of
      striatal dysmorphology in patients with chronic cocaine dependence. METHOD:
      Caudate, putamen, and total brain volumes were quantified by means of magnetic
      resonance imaging in 25 cocaine-dependent and 20 healthy subjects. RESULTS:
      Normalized caudate and putamen volumes were 3.40% and 9.18% larger, respectively,
      in the cocaine-dependent subjects. CONCLUSIONS: These observations suggest that
      deficits in dopaminergic function associated with cocaine dependence may
      contribute to striatal hypertrophy.

PMID- 11229996
TI  - Evidence of a cohort effect for age at onset of schizophrenia.
AB  - OBJECTIVE: The authors address whether a possible age-at-onset cohort effect may
      have introduced a bias into anticipation studies of schizophrenia. METHOD: A
      retrospective review of the medical records of all admissions for psychotic
      disorders (N=877) was conducted. All subjects with a confirmed DSM-IV diagnosis
      of schizophrenia and age-at-onset data were included (N=419). For analyses,
      subjects were placed into one of three successive birth cohorts: 1905-1944
      (N=96), 1945-1964 (N=200), and 1965-1984 (N=123). RESULTS: The mean age at first
      appearance of psychotic symptoms and, similarly, the mean age at first
      hospitalization significantly decreased over time in successive birth cohorts
      (25.3, 23.3, and 20.4 years, respectively, for age at first appearance of
      psychotic symptoms). CONCLUSIONS: This potential birth cohort effect for age at
      onset of schizophrenia needs to be incorporated into genetic models.

PMID- 11229997
TI  - Is substance abuse in schizophrenia related to impulsivity, sensation seeking, or
      anhedonia?
AB  - OBJECTIVE: The authors compared impulsivity, sensation seeking, and anhedonia in
      a group of schizophrenic patients with and without lifetime substance abuse or
      dependence. METHOD: Patients (N=100) with schizophrenia or schizoaffective
      disorder (per DSM-III-R criteria) were assessed with the Composite International
      Diagnostic Interview's section on psychoactive substance use disorder, the
      Positive and Negative Syndrome Scale, the Barratt Impulsivity Scale, the
      Zuckerman Seeking Sensation Scale, and the Chapman Physical Anhedonia Scale.
      RESULTS: The mean scores for impulsivity and sensation seeking were higher in the
      group with substance abuse (N=41) than in the group without substance abuse
      (N=59). No significant difference between groups was found regarding physical
      anhedonia. CONCLUSIONS: As in the general population, high levels of impulsivity
      and sensation seeking are associated with substance abuse in patients with
      schizophrenia.

PMID- 11229998
TI  - Right frontal hypergyria differentiation in affected and unaffected siblings from
      families multiply affected with schizophrenia: a morphometric mri study.
AB  - OBJECTIVE: The authors used magnetic resonance imaging to corroborate the
      postmortem finding of right frontal hypergyria associated with schizophrenia.
      METHOD: Twelve affected-unaffected sibling pairs from families multiply affected
      with schizophrenia were studied. Bilateral measurement of the gyrification index,
      the ratio of the inner and outer surface contours, was performed on three
      different slices of the prefrontal region. RESULTS: The mean gyrification index
      on the right side was significantly higher in siblings with schizophrenia or
      schizoaffective disorder than in the unaffected siblings. CONCLUSIONS: In this
      family cohort study, the postmortem finding of right-sided hypergyria in subjects
      with schizophrenia was replicated in vivo with magnetic resonance imaging. This
      observation provides further support for a neurodevelopmental mechanism in the
      pathogenesis of schizophrenia.

PMID- 11229999
TI  - Schizophrenia and pathological gambling.

PMID- 11230000
TI  - Cutaneous vasculitis induced by paroxetine.

PMID- 11230001
TI  - Pramipexole augmentation in panic with agoraphobia.

PMID- 11230002
TI  - Gabapentin for misuse of homemade nicotine nasal spray.

PMID- 11230003
TI  - Clozapine and pulmonary embolus.

PMID- 11230004
TI  - Low blood glucose and olanzapine.

PMID- 11230005
TI  - Does pharmaceutical research prevail?

PMID- 11230007
TI  - Differing tolerability profiles among atypical antipsychotics.

PMID- 11230009
TI  - Diagnosing Asperger's disorder.

PMID- 11230011
TI  - Chronic late-onset schizophrenia-like psychosis.

PMID- 11230013
TI  - Obsessive-compulsive disorder and bulimia.

PMID- 11230026
TI  - Placebo response in depression: bane of research, boon to therapy.

PMID- 11230027
TI  - Implementing evidence-based psychiatry: whose responsibility?

PMID- 11230028
TI  - The tendency to stigmatise.

PMID- 11230029
TI  - Cognitive deficits in depression: possible implications for functional
      neuropathology.
AB  - BACKGROUND: While depression is known to involve a disturbance of mood, movement
      and cognition, its associated cognitive deficits are frequently viewed as simple
      epiphenomena of the disorder. AIMS: To review the status of cognitive deficits in
      depression and their putative neurobiological underpinnings. METHOD: Selective
      computerised review of the literature examining cognitive deficits in depression
      and their brain correlates. RESULTS: Recent studies report both mnemonic deficits
      and the presence of executive impairment--possibly selective for set-shifting
      tasks--in depression. Many studies suggest that these occur independent of age,
      depression severity and subtype, task 'difficulty', motivation and response bias:
      some persist upon clinical 'recovery'. CONCLUSIONS: Mnemonic and executive
      deficits do no appear to be epiphenomena of depressive disorder. A focus on the
      interactions between motivation, affect and cognitive function may allow greater
      understanding of the interplay between key aspects of the dorsal and ventral
      aspects of the prefrontal cortex in depression.

PMID- 11230030
TI  - A unitary theory of stigmatisation: pursuit of self-interest and routes to
      destigmatisation.
AB  - BACKGROUND: Stigmatisation is of increasing importance in relation to racism,
      ageism and sexism but also as an impediment to treating patients. AIMS: To
      develop a theoretical foundation to help comprehend the core meaning of
      stigmatisation and to guide practical anti-stigmatisation measures. METHOD:
      Personal reflection; re-interpretation of stigmatisation and reformulation of the
      relevant concepts. RESULTS: Emergence of a unitary theory of stigmatisation.
      CONCLUSIONS: Based on the structure of stigmatisation one could explore six
      levels of intervention in anti-stigmatisation campaigns: the cognitive level -
      educational intervention; the affective level - psychological intervention; the
      discrimination level - legislative intervention; the denial level - linguistic
      intervention; the economic origin - political intervention; the evolutionary
      origin - intellectual and cultural intervention. As destigmatisation has to
      challenge fundamental human tendencies, anti-stigmatisation campaigns have to be
      continuous, non-stop, open-ended projects aiming at keeping alive thought
      processes that moderate and humanise the pursuit of self-interest and the urge to
      survive in a competitive world.

PMID- 11230031
TI  - Psychological therapies for adults with anorexia nervosa: randomised controlled
      trial of out-patient treatments.
AB  - BACKGROUND: Currently, without systematic evidence, psychotherapy for anorexia
      nervosa in adults draws on psychodynamic, cognitive and systemic theories. AIMS:
      To assess effectiveness of specific psychotherapies in out-patient management of
      adult patients with anorexia nervosa. METHOD: Eighty-four patients were
      randomised to four treatments: three specific psychotherapies - (a) a year of
      focal psychoanalytic psychotherapy; (b) 7 months of cognitive-analytic therapy
      (CAT); (c) family therapy for 1 year - and (d) low contact, 'routine' treatment
      for 1 year (control). RESULTS: At 1 year, there was symptomatic improvement in
      the whole group of patients. This improvement was modest, several patients being
      significantly undernourished at follow-up. Psychoanalytic psychotherapy and
      family therapy were significantly superior to the control treatment; CAT tended
      to show benefits. CONCLUSIONS: Psychoanalytic and family therapy are of specific
      value in the out-patient treatment of adult patients with anorexia.

PMID- 11230032
TI  - Income inequality and the prevalence of common mental disorders in Britain.
AB  - BACKGROUND: It has been hypothesised that the association between greater income
      inequality and increased mortality is mediated by poor psychosocial health. AIMS:
      To test the hypothesis that individuals in regions of Britain with the highest
      income inequality have a higher prevalence of the common mental disorders, after
      adjusting for individual income. METHOD: Cross-sectional survey of 8191 adults
      aged 16-75 in private households in England, Wales and Scotland. The prevalence
      of common mental disorders was assessed using the General Health Questionnaire.
      RESULTS: The association between income inequality and prevalence of the common
      mental disorders varied with individual income level. Among persons with the
      highest incomes, common mental disorders were more frequent in regions with
      greater income inequality (as indicated by high Gini coefficient) (adjusted OR
      1.31,95% C1 1.05-1.65; P: = 0.02). The opposite was true for those with the
      lowest incomes. CONCLUSIONS: Income inequality was associated with worse mental
      health among the most affluent individuals.

PMID- 11230033
TI  - Common mental disorders in Santiago, Chile: prevalence and socio-demographic
      correlates.
AB  - BACKGROUND: There have been relatively few surveys in Latin America that have
      attempted to estimate the prevalence of psychiatric morbidity in private
      households. AIMS: To determine the prevalence of common mental disorders and
      socio-demographic correlates among adults from Santiago, Chile. METHOD: Cross
      sectional survey of private households with a probabilistic sampling design was
      used. Common mental disorders were measured using the Clinical Interview Schedule
      Revised (CIS-R). RESULTS: Three thousand eight hundred and seventy adults were
      interviewed. Twenty-five per cent were CIS-R cases and 13% met criteria for an
      ICD-10 diagnosis. Low education, female gender, unemployment, separation, low
      social status and lone parenthood were associated with a higher prevalence.
      CONCLUSIONS: Prevalence rates were higher than those found in urban areas of
      Great Britain, both for ICD-10 diagnoses and 'non-specific neurotic disorders'.
      Similar socio-demographic factors were associated with an increased prevalence of
      common mental disorders in Chile as in the UK. There is a need to unify
      methodologies to be able to compare results internationally.

PMID- 11230034
TI  - Remission rates during treatment with venlafaxine or selective serotonin reuptake
      inhibitors.
AB  - BACKGROUND: It had been suggested that the antidepressant venlafaxine, which
      inhibits reuptake of both serotonin and (at higher doses) noradrenaline, may
      result in better outcomes than treatment with selective serotonin reuptake
      inhibitors (SSRIs). AIMS: To compare remission rates during treatment with SSRIs
      or venlafaxine. METHOD: Data from eight comparable randomised, double-blind
      studies of major depressive disorder were pooled to compare remission rates
      (Hamilton Rating Scale for Depression score < or = 7) during treatment with
      venlafaxine (n = 851), SSRIs (fluoxetine, paroxetine, fluvoxamine; n = 748) or
      placebo (four studies; n = 446). RESULTS: Remission rates were: venlafaxine, 45%
      (382/851); SSRIs, 35% (260/748); placebo, 25% (110/446) (P: < 0.001; odds ratio
      for remission is 1.50 (1.3-1.9), favouring venlafaxine v. SSRIs). The difference
      between venlafaxine and the SSRIs was significant at week 2, whereas the
      difference between SSRIs and placebo reached significance at week 4. Results were
      not dependent on any one study or the definition of remission. CONCLUSIONS:
      Remission rates were significantly higher with venlafaxine than with an SSRI.

PMID- 11230035
TI  - Psychiatric battle casualties: an intra- and interwar comparison.
AB  - BACKGROUND: Psychiatric casualties are recognised as an important and inevitable
      feature of modern warfare. At the beginning of the 20th century they were
      scarcely acknowledged and still less treated. Today, as a result of lessons
      learned in the First and Second World Wars, numbers can be predicted on the basis
      of battle intensity and effective clinical interventions applied. AIMS: To
      discover more about the factors that cause psychiatric casualties and their
      relationship to total battle casualties. METHOD: A survey of historical War
      Office reports and the papers of Royal Army Medical Corps psychiatrists has
      provided both statistics and treatment strategies. RESULTS: Reported psychiatric
      casualties were low in the Boer War, influenced, in part, by the misdiagnosis of
      psychosomatic disorders. Their incidence rose appreciably in the First World War
      with the identification of shell-shock and neurasthenia. The Second World War saw
      the collection of accurate data, and combat stress was treated efficiently,
      although few soldiers returned to fighting units. CONCLUSIONS: A constant
      relationship exists between the incidence of the total killed and wounded and the
      number of psychiatric casualties, mediated by the nature of the fighting and
      quality of the troops involved.

PMID- 11230036
TI  - Relatives of patients with severe psychotic disorders: factors that influence
      contact frequency. Report from the UK700 trial.
AB  - BACKGROUND: The isolation experienced by many patients with severe psychotic
      disorders is generally assumed to be due to their social withdrawal. An
      alternative possibility is that relatives avoid frequent contact with patients
      because they find the situation distressing. AIMS: To examine the predictors of
      frequent patient-relative contact, in particular the role of relatives'
      experience. METHOD: UK700 trial data were used to determine baseline predictors
      of frequent contact and establish whether relatives' experience at baseline
      predicted continued frequent contact 2 years later. RESULTS: Neither
      characteristics associated in the literature with relatives' 'burden' nor
      relatives' experience predicted patient-relative contact frequency. Instead, the
      predictors were mainly demographic. CONCLUSIONS: Many relatives experience
      considerable distress, but the evidence does not suggest that they avoid frequent
      contact with the patient as a consequence.

PMID- 11230037
TI  - Suicidal behaviour in psychosis: prevalence and predictors from a randomised
      controlled trial of case management: report from the UK700 trial.
AB  - BACKGROUND: It is unclear whether intensive case management influences the
      prevalence of suicidal behaviour in patients with psychosis. AIMS: To compare the
      effect of intensive case management and standard care on prevalence of suicidal
      behaviour in patients with chronic psychosis. METHOD: Patients with established
      psychosis (n = 708) were randomised either to intensive case management or to
      standard care. The prevalence of suicidal behaviour was estimated at 2-year
      follow-up and compared between treatment groups. Suicide attempters and non
      attempters were compared on multiple socio-demographic and clinical variables to
      identify predictors of suicidal behaviour. RESULTS: There was no significant
      difference in prevalence of suicidal behaviour between treatment groups. Recent
      attempts at suicide and multiple recent hospital admissions best predicted future
      attempts. CONCLUSIONS: Intensive case management does not appear to influence the
      prevalence of suicidal behaviour in chronic psychosis. Predictors identified in
      this study confirm some previous findings.

PMID- 11230038
TI  - Changes in the quality of life of patients receiving antidepressant medication in
      primary care: validation of the WHOQOL-100.
AB  - BACKGROUND: The study arises from the need for good quality of life (QOL)
      assessment and a new comprehensive generic QOL profile for cross-cultural use.
      AIMS: To examine changes in the QOL of patients receiving antidepressants from a
      general practitioner, and to assess the validity and sensitivity of a new QOL
      measure, the World Health Organization Quality of Life Assessment (100-item
      version) (WHOQOL-100). METHOD: Patients with moderate depression (n = 106)
      completed the WHOQOL-100 and Beck Depression Inventory at the start of treatment
      and again after 6 weeks. RESULTS: Depression decreased significantly over 2
      months and 74% reported feeling better. WHOQOL-100 scores increased in 24 of the
      25 facets, demonstrating that QOL improves significantly in the 8 weeks following
      the start of antidepressant treatment. It also shows the instrument's validity
      and sensitivity to changes in clinical condition. CONCLUSIONS: The UK WHOQOL-100
      is confirmed as excellent to good. Antidepressants significantly and
      comprehensively improve QOL.

PMID- 11230040
TI  - Patients and clients.

PMID- 11230039
TI  - Subjective and objective dimensions of quality of life in psychiatric patients: a
      factor analytical approach: The South Verona Outcome Project 4.
AB  - BACKGROUND: Both subjective and objective information is necessary to assess
      quality of life (QOL). AIMS: To explore the role of subjective and objective QOL
      dimensions and their cross-sectional and longitudinal predictors. METHOD: The
      relationship between QOL, as measured by the Lancashire Quality of Life Profile
      (LQL), and demographic variables, diagnosis, psychopathology, disability,
      functioning, affect balance, self-esteem, service use and service satisfaction
      was investigated at two points in time, using factor analysis and multiple
      regression techniques. RESULTS: One subjective and two objective LQL factors with
      strong face validity were identified. Cross-sectional predictors of the
      subjective factor were primarily subjective measures; longitudinally, few
      predictors of this factor were identified. The cross-sectional and longitudinal
      predictors of the objective factors were primarily demographic and observer-rated
      measures. CONCLUSIONS: Subjective and objective data are distinct types of
      information. Objective measures may be more suitable in detecting treatment
      effects. Subjective information is necessary to complete the QOL picture and to
      enhance the interpretation of objective data.

PMID- 11230041
TI  - Book reviews in the electronic age.

PMID- 11230042
TI  - Evolutionary theory and psychiatry.

PMID- 11230043
TI  - Book reviews in the electronic age.

PMID- 11230044
TI  - National Service Framework and suicide.

PMID- 11230045
TI  - Near-fatal methylphenidate misuse.

PMID- 11230046
TI  - What constitutes intensive treatment?

PMID- 11230050
TI  - New approach to the consultant contract.

PMID- 11230049
TI  - Medical errors: a common problem.

PMID- 11230051
TI  - Using clinical evidence.

PMID- 11230053
TI  - Controlling infection in British nursing homes. It is time for a national
      strategy.

PMID- 11230052
TI  - Higher dose inhaled corticosteroids in childhood asthma.

PMID- 11230054
TI  - BMA may seek legal challenge over curbs on private practice.

PMID- 11230055
TI  - Not again! Patients must be properly informed to agree to or decline treatment.

PMID- 11230056
TI  - UK sets up fund to improve child health in Commonwealth.

PMID- 11230057
TI  - Professor faces GMC for failure to prevent and report fraud.

PMID- 11230058
TI  - New UK guidance on resuscitation calls for open decision making.

PMID- 11230059
TI  - Dutch GP found guilty of murder faces no penalty.

PMID- 11230060
TI  - Breast feeding safer than mixed feeding for babies of HIV mothers.

PMID- 11230063
TI  - Cross sectional study of young people's awareness of and involvement with tobacco
      marketing.
AB  - OBJECTIVES: To examine young people's awareness of and involvement with tobacco
      marketing and to determine the association, if any, between this and their
      smoking behaviour. DESIGN: Cross sectional, quantitative survey, part interview
      and part self completion, administered in respondents' homes. SETTING: North east
      England. PARTICIPANTS: Stratified random sample of 629 young people aged 15 and
      16 years who had "opted in" to research through a postal consent procedure.
      RESULTS: There was a high level of awareness of and involvement in tobacco
      marketing among the 15-16 year olds sampled in the study: around 95% were aware
      of advertising and all were aware of some method of point of sale marketing.
      Awareness of and involvement with tobacco marketing were both significantly
      associated with being a smoker: for example, 30% (55/185) of smokers had received
      free gifts through coupons in cigarette packs, compared with 11% (21/199) of non
      smokers (P<0.001). When other factors known to be linked with teenage smoking
      were held constant, awareness of coupon schemes, brand stretching, and tobacco
      marketing in general were all independently associated with current smoking
      status. CONCLUSIONS: Teenagers are aware of, and are participating in, many forms
      of tobacco marketing, and both awareness and participation are associated with
      current smoking status. This suggests that the current voluntary regulations
      designed to protect young people from smoking are not working, and that statutory
      regulations are required.

PMID- 11230064
TI  - Adverse events in British hospitals: preliminary retrospective record review.
AB  - OBJECTIVES: To examine the feasibility of detecting adverse events through record
      review in British hospitals and to make preliminary estimates of the incidence
      and costs of adverse events. DESIGN: Retrospective review of 1014 medical and
      nursing records. SETTING: Two acute hospitals in Greater London area. MAIN
      OUTCOME MEASURE: Number of adverse events. RESULTS: 110 (10.8%) patients
      experienced an adverse event, with an overall rate of adverse events of 11.7%
      when multiple adverse events were included. About half of these events were
      judged preventable with ordinary standards of care. A third of adverse events led
      to moderate or greater disability or death. CONCLUSIONS: These results suggest
      that adverse events are a serious source of harm to patients and a large drain on
      NHS resources. Some are major events; others are frequent, minor events that go
      unnoticed in routine clinical care but together have massive economic
      consequences.

PMID- 11230065
TI  - Involving consumers in designing, conducting, and interpreting randomised
      controlled trials: questionnaire survey.
AB  - OBJECTIVE: To assess the extent to which consumers are involved in the work of
      clinical trial coordinating centres in the United Kingdom and the nature of
      consumers' involvement in randomised trials coordinated by these centres. DESIGN:
      National surveys using structured questionnaires with some open ended sections.
      SETTING: 103 clinical trial coordinating centres in the United Kingdom identified
      through a database assembled in 1997 by the NHS clinical trials adviser.
      PARTICIPANTS: Named contacts at 62 coordinating centres and investigators in 60
      trials that were identified as involving consumers. MAIN OUTCOME MEASURES: Number
      of coordinating centres and number of trials in which consumers were involved and
      the nature of consumers' involvement. RESULTS: Of the 62 eligible centres, 23
      reported that consumers had already been involved in their work, and most
      respondents were positive about this involvement. 17 centres planned to involve
      consumers. 15 centres had no plans to involve consumers, but only four of these
      considered such involvement irrelevant. Responses from investigators about the 48
      individual trials were mostly positive, with respondents commenting that input
      from consumers had helped refine research questions, improve the quality of
      patient information, and make the trial more relevant to the needs of patients.
      CONCLUSIONS: Consumer involvement in the design and conduct of controlled trials
      seems to be growing and seems to be welcomed by most researchers. Such
      involvement seems likely to improve the relevance to consumers of the questions
      addressed and the results obtained in controlled trials.

PMID- 11230066
TI  - Management of menorrhagia: an audit of practices in the Anglia menorrhagia
      education study.

PMID- 11230067
TI  - Violence by clients towards female prostitutes in different work settings:
      questionnaire survey.

PMID- 11230068
TI  - Women's understanding of a "normal smear test result": experimental questionnaire
      based study.
AB  - OBJECTIVES: To describe women's understanding of a negative smear test result
      when presented using the term "normal smear result," as required by the NHS
      cervical screening programme, and to evaluate the impact on understanding of
      different ways of presenting the residual risk inherent in such a result. DESIGN:
      Experimental questionnaire based study. INTERVENTIONS: Participants were asked to
      imagine that they had received a normal smear result. The meaning of this result
      was then presented using different combinations of three different expressions of
      residual risk of having or developing cervical cancer over the next five years: a
      verbal probability of absolute risk (low risk), a numerical probability of
      absolute risk (1 in 5000), or a numerical probability of risk relative to an
      unscreened woman (five times lower). PARTICIPANTS: 1027 women aged 20 to 64.
      RESULTS: When informed only that their smear result was normal, 52% (80 of 153
      women) of participants correctly understood that this entailed a residual risk of
      cervical cancer, compared with 70% (107 of 152) given the additional sentence
      explaining the meaning of a normal smear result using a verbal probability of
      absolute risk (difference 18%; 95% confidence interval 7% to 29%). Additionally,
      explaining the results using a numerical probability of absolute or relative risk
      did not increase the proportion who correctly understood that there was a
      residual risk of cervical cancer. CONCLUSIONS: NHS policy for reporting normal
      smears needs to change to make it a definite requirement that the reporting of a
      "normal smear result" is accompanied by a sentence stating that this means a low
      risk for having or developing cervical cancer in the next five years.

PMID- 11230069
TI  - Just in time information for clinicians: a questionnaire evaluation of the
      ATTRACT project.

PMID- 11230070
TI  - Publishing raw data and real time statistical analysis on e-journals.

PMID- 11230072
TI  - ABC of diseases of liver, pancreas, and biliary system.

PMID- 11230071
TI  - Blood pressure measuring devices: recommendations of the European Society of
      Hypertension.

PMID- 11230073
TI  - Reforming the contract of UK consultants.

PMID- 11230074
TI  - Health needs of asylum seekers and refugees.

PMID- 11230075
TI  - Data protection and patients' consent. GMC is greater threat to research than the
      act.

PMID- 11230076
TI  - Mortality in joggers. Benefits are seen in previously sedentary individuals who
      start exercising regularly.

PMID- 11230077
TI  - Data protection and patients' consent. New Zealand model of consent offers
      solution.

PMID- 11230078
TI  - Accuracy of ATLS guidelines for predicting systolic blood pressure. No one relies
      on pulse checks alone for subsequent clinical decision making.

PMID- 11230079
TI  - Safeguards for research using large scale DNA collections. Educational
      initiatives are essential for success of population genetic studies.

PMID- 11230080
TI  - Accuracy of ATLS guidelines for predicting systolic blood pressure. Earlier dogma
      seems to have been dropped now.

PMID- 11230081
TI  - Mortality in joggers. Healthy jogger effect might explain differences in
      mortality.

PMID- 11230082
TI  - Tobacco industry must not dump its high nitrosamine tobacco on poor countries.

PMID- 11230083
TI  - Not again! Designing safer medical devices requires financial and political
      support.

PMID- 11230084
TI  - Not again! Erroneous intrathecal injection results from a problem with protocols.

PMID- 11230085
TI  - Data protection and patients' consent. Informed consent should be sought before
      data are used by registries.

PMID- 11230086
TI  - Not again! National guidelines are urgently needed.

PMID- 11230087
TI  - Safeguards for research using large scale DNA collections. Study will not be
      started before suitable arrangements are in place.

PMID- 11230088
TI  - Not again! Only ocular treatments should be packaged like eye drops.

PMID- 11230089
TI  - Accuracy of ATLS guidelines for predicting systolic blood pressure. Authors' core
      assertion was wrong.

PMID- 11230090
TI  - Not again! Packaging of lignocaine must be changed.

PMID- 11230091
TI  - Feature article: the structure and function of dynamic cortical and thalamic
      receptive fields.
AB  - Under natural conditions, animals must process spatiotemporally complex signals
      in order to guide adaptive behavior. It follows that the response properties of
      neurons should reflect the dynamic nature of such signals. Recently, several
      studies have demonstrated the existence of time-varying receptive fields in the
      auditory, visual and somatosensory thalamocortical pathways. The characteristics
      of these receptive fields suggest that they are constrained by the need to
      actively interpret time-varying stimuli. Here, we review these studies, the
      possible functions of these receptive fields, and how they might be generated in
      the thalamocortical pathway.

PMID- 11230092
TI  - Perinatal-lesion-induced reorganization of cerebral functions revealed using
      reversible cooling deactivation and attentional tasks.
AB  - We tested the concept that lesions of primary visual cortical areas 17 and 18
      sustained on the day of birth induce a redistribution of cerebral operations
      underlying the ability to disengage visual attention and then redirect it to a
      new location. In cats, these operations are normally highly localizable to
      posterior middle suprasylvian (pMS) cortex. Three stimulation paradigms were
      used: (i) movement of a high contrast visual stimulus into the visual field; (ii)
      illumination of a static light-emitting diode (LED) stimulus; and (iii) a control
      static auditory stimulus. To test for the redistribution of critical neural
      operations, cryoloops were implanted bilaterally in the pMS sulcus and in contact
      with ventral posterior suprasylvian (vPS) cortex. Separate and combined
      deactivations of pMS and vPS cortices in cats with early lesions of primary
      visual cortex showed that full, unilateral deactivation of pMS cortex only
      partially impaired the ability to detect and orient to stimuli moved into the
      contracooled hemifield. Much more complete impairment required the additional
      deactivation of ipsilateral vPS cortex. Bilateral pMS deactivation alone, or in
      combination with bilateral vPS deactivation, largely reversed the unilateral
      contracooled neglect. For the orienting to static, illuminated LED stimuli,
      unilateral deactivation of pMS cortex was sufficient to fully impair orienting to
      stimuli presented in the contracooled hemifield. Bilateral pMS deactivation
      induced an almost complete visual-field-wide neglect of stimuli. On its own,
      unilateral deactivation of vPS cortex was without effect on either task, although
      bilateral vPS deactivations introduced inconsistencies into the performance.
      Termination of cooling reversed all deficits. Finally, neither the initial lesion
      of areas 17 and 18 nor cooling of either the MS or vPS cortex alone, or in
      combination, interfered with orienting to sound stimuli. Overall, our results
      provide evidence that at least one highly localizable visual function of normal
      cerebral cortex is remapped across the cortical surface following the early
      lesion of primary visual cortical areas 17 and 18. Moreover, the redistribution
      has spread the essential neural operations from the visual parietal cortex to a
      normally functionally distinct type of cortex in the visual temporal system.

PMID- 11230093
TI  - Interval and ordinal properties of sequences are associated with distinct
      premotor areas.
AB  - Lesion and imaging studies have suggested that the premotor cortex (PMC) is a
      crucial component in the neural network underlying the processing of sequential
      information. However, whether different aspects of sequential information like
      interval and ordinal properties are supported by different anatomical regions,
      and whether the representation of sequential information within the PMC is
      necessarily related to motor requirements, remain open questions. Brain
      activations were investigated during a sequence encoding paradigm in 12 healthy
      subjects using functional magnetic resonance imaging. Subjects had to attend
      either to the interval or to the ordinal information of a sequence of visually
      presented stimuli and had to encode the relevant information either before motor
      reproduction or before perceptual monitoring. Although interval and ordinal
      information led to activations within the same neural network, direct comparisons
      revealed significant differences. The pre-supplementary motor area (preSMA), the
      lateral PMC, the frontal opercular cortex as well as basal ganglia and the left
      lateral cerebellar cortex (CE) were activated significantly more strongly by
      interval information, whereas the SMA, the frontal eye field, the primary motor
      cortex (MI), the primary somatosensory cortex, the cuneus as well as the medial
      CE and the thalamus were activated more strongly by ordinal information. In
      addition, serial encoding before reproduction led to higher activations than
      serial encoding before monitoring in the preSMA, SMA, MI and medial CE. Our
      findings suggest overlapping but different kinds of sequential representation,
      depending on both the ordinal and interval aspects as well as motor requirements.

PMID- 11230094
TI  - The neural bases of sentence comprehension: a fMRI examination of syntactic and
      lexical processing.
AB  - One of the challenges to functional neuroimaging is to understand how the
      component processes of reading comprehension emerge from the neural activity in a
      network of brain regions. In this study, functional magnetic resonance imaging
      (fMRI) was used to examine lexical and syntactic processing in reading
      comprehension by independently manipulating the cognitive demand on each of the
      two processes of interest. After establishing a consistency with earlier research
      showing the involvement of the left perisylvian language areas in both lexical
      access and syntactic processing, the study produced new findings that are
      surprising in two ways: (i) the lexical and syntactic factors each impact not
      just individual areas, but they affect the activation in a network of left
      hemisphere areas, suggesting that changing the computational load imposed by a
      given process produces a cascade of effects in a number of collaborating areas;
      and (ii) the lexical and syntactic factors usually interact in determining the
      amount of activation in each affected area, suggesting that comprehension
      processes that operate on different levels of language may nevertheless draw on a
      shared infrastructure of cortical resources. The results suggest that many
      processes in sentence comprehension involve multiple brain regions, and that many
      brain regions contribute to more than one comprehension process. The implication
      is that the language network consists of brain areas which each have multiple
      relative specializations and which engage in extensive interarea collaborations.

PMID- 11230095
TI  - Presence of both constitutive and inducible forms of heat shock protein 70 in the
      cerebral cortex and hippocampal synapses.
AB  - Heat shock proteins serve as molecular chaperones in a protein "holding and
      folding" system. Protein sequencing, extraction and immunoblot analyses indicate
      that Hsc70, a constitutive form, is a major component of the rat postsynaptic
      density (PSD) fraction, while Hsp70, an inducible form, is present at the basal
      level. Immunohistochemical studies show that expression of Hsc70 is high, but
      that of Hsp70 is low, in the cerebral cortex and hippocampal formation. In
      dissociated hippocampal neurons, both Hsp70 and Hsc70 immunoreactivities are
      distributed throughout the soma and dendrites. In dendrites, there are many
      stained puncta which are mostly co-localized with PSD-95, a postsynaptic marker.
      Interestingly, variation in staining intensity of the puncta is significantly
      larger for Hsp70 than for Hsc70 in 2-week-old cultures, but becomes less
      significant in 5(1/2)-week-old cultures. At the electron microscopic level, both
      Hsp70 and Hsc70 are mainly associated with asymmetrical PSDs. However, Hsc70 is
      also associated with amorphous subsynaptic structures and spine apparatus-like
      cisternae. Our data indicate that both Hsp70 and Hsc70 are present in PSDs but
      are differentially distributed at subsynaptic sites, and provide a potential
      candidate system for a "synaptic tag".

PMID- 11230096
TI  - Anoxic depolarization mediates acute damage independent of glutamate in
      neocortical brain slices.
AB  - An important but poorly understood event associated with ischemia is anoxic
      depolarization (AD), a sudden and profound depolarization of neurons and glia in
      cortical and subcortical gray matter. Leao first measured the AD as a wave of
      electrical silence moving across the cerebral cortex in 1947 and noted its
      similarity to spreading depression (SD). SD is harmless when coursing through
      normoxic cortical tissue as during migraine aura. However for 3-4 h following
      focal ischemia, the additional metabolic stress arising from recurring SD in the
      penumbra expands the ischemic core, so SD blockade is potentially beneficial
      therapeutically. In the present study, we measured intrinsic optical signals
      (IOSs) to monitor anoxic depolarization in submerged rat neocortical slices
      during O2/glucose deprivation (OGD). After approximately 6 min of OGD, the AD was
      imaged as a focal increase in light transmittance which then propagated across
      neocortical gray at approximately 2 mm/min. Although the slice was globally
      stressed, the AD always initiated focally, sometimes at multiple sites. Its
      propagation was coincident with a transient negative shift in the extracellular
      potential, the electrical signature of AD. Acute damage to neocortex (measured as
      a delayed decrease in LT and as a loss of the evoked field potential) followed
      only where the AD had propagated, so it is the combined metabolic demands of AD
      and OGD that acutely damages all layers of the neocortex. Glutamate receptor
      antagonists (2 mM kynurenate or 25 microM AP-5/10 microM CNQX) did not block AD
      initiation, slow its propagation or prevent post-AD damage. This study shows that
      acute ischemic damage is greatly exacerberated by AD during metabolic stress and
      that glutamate receptor antagonists are not protective. Using this slice model,
      therapeutically tolerable drugs that block the AD and SD can be investigated.

PMID- 11230097
TI  - The role of dorsolateral prefrontal cortex in the preparation of forthcoming
      actions: an fMRI study.
AB  - The dorsolateral prefrontal cortex (DLPFC) plays a key role in working memory
      (WM). Yet its precise contribution (the storage, manipulation and/or utilization
      of information for the forthcoming response) remains to be determined. To test
      the hypothesis that the DLPFC is more involved in the preparation of actions than
      in the maintenance of information in short-term memory (STM), we undertook a
      functional magnetic resonance imaging investigation in normal subjects performing
      two delayed response tasks (matching and reproduction tasks) in a visuospatial
      task sequence (presentation, delay, response). In the two tasks, the presentation
      and delay phases were similar, but the expected response was different: in the
      matching task, subjects had to indicate whether a visuospatial sequence matched
      the sequence presented before the delay period; in the reproduction task,
      subjects had to reproduce the sequence and, therefore, to mentally organize their
      response during the delay. Using a fMRI paradigm focusing on the delay period, we
      observed a significant DLPFC activation when subjects were required to mentally
      prepare a sequential action based on the information stored in STM. When subjects
      had only to maintain a visuospatial stimulus in STM, no DLPFC activation was
      found. These results suggest that a parietal-premotor network is sufficient to
      store visuospatial information in STM whereas the DLPFC is involved when it is
      necessary to mentally prepare a forthcoming sequential action based on the
      information stored in STM.

PMID- 11230098
TI  - Conjoint and extended neural networks for the computation of speech codes: the
      neural basis of selective impairment in reading words and pseudowords.
AB  - The computation of speech codes (i.e. phonology) is an important aspect of word
      reading. Understanding the neural systems and mech- anisms underlying
      phonological processes provides a foundation for the investigation of language in
      the brain. We used high-resolution three-dimensional positron emission tomography
      (PET) to investigate neural systems essential for phonological processes. The
      burden of neural activities on the computation of speech codes was maximized by
      three rhyming tasks (rhyming words, pseudowords and words printed in mixed letter
      cases). Brain activation patterns associated with these tasks were compared with
      those of two baseline tasks involving visual feature detection. Results suggest
      strong left lateralized epicenters of neural activity in rhyming irrespective of
      gender. Word rhyming activated the same brain regions engaged in pseudoword
      rhyming, suggesting conjoint neural networks for phonological processing of words
      and pseudowords. However, pseudoword rhyming induced the largest change in
      cerebral blood flow and activated more voxels in the left posterior prefrontal
      regions and the left inferior occipital-temporal junction. In addition,
      pseudoword rhyming activated the left supramarginal gyrus, which was not apparent
      in word rhyming. These results suggest that rhyming pseudowords requires active
      participation of extended neural systems and networks not observed for rhyming
      words. The implications of the results on theories and models of visual word
      reading and on selective reading dysfunctions after brain lesions are discussed.

PMID- 11230099
TI  - Axonal surface molecules act in combination with semaphorin 3a during the
      establishment of corticothalamic projections.
AB  - Interactions between growing axons are considered to play important roles for the
      establishment of precise neuronal connections during the development of the
      nervous system. Here we used time-lapse imaging techniques to examine the
      behavior of neocortical and thalamic axons when they encounter each other in
      vitro. Results indicate that axonal growth cones are able to respond to specific
      cues expressed on the surface of fibers. Thalamic growth cones often extended
      along the surface of other thalamic axons and, likewise, cortical growth cones
      formed fascicles with cortical axons. In contrast, after contacts between
      cortical and thalamic fibers, in most cases growth cones collapsed and retracted
      from the axons. Collapse assays using membrane preparations from cortical or
      thalamic explants demonstrated the existence of cell-type specific collapsing
      factors whose activity was enhanced by a member of the semaphorin protein family,
      Sema3A (expressed in the thalamocortical pathway), as it increased the rate of
      homotypic fasciculations and at the same time amplified the segregation between
      cortical and thalamic axons. The interaction between axonal surface molecules and
      environmental cues might mediate the segregation of afferent and efferent fiber
      tracts in the neocortical white matter.

PMID- 11230100
TI  - Cyclin-dependent kinase-2 in the birth and death of cardiac muscle cells.

PMID- 11230101
TI  - Getting to the heart of cardiac morphogenesis.

PMID- 11230102
TI  - Adenoviral-mediated serca gene transfer into cardiac myocytes: how much is too
      much?

PMID- 11230103
TI  - Reverse mode of the Na+-Ca2+ exchange after myocardial stretch: underlying
      mechanism of the slow force response.
AB  - This study was designed to gain additional insight into the mechanism of the slow
      force response (SFR) to stretch of cardiac muscle. SFR and changes in
      intracellular Na(+) concentration ([Na(+)](i)) were assessed in cat papillary
      muscles stretched from 92% to approximately 98% of L(max). The SFR was 120+/-0.6%
      (n=5) of the rapid initial phase and coincided with an increase in [Na(+)](i).
      The SFR was markedly depressed by Na(+)-H(+) exchanger inhibition, AT(1) receptor
      blockade, nonselective endothelin-receptor blockade and selective ET(A)-receptor
      blockade, extracellular Na(+) removal, and inhibition of the reverse mode of the
      Na(+)-Ca(2+) exchange by KB-R7943. KB-R7943 prevented the SFR but not the
      increase in [Na(+)](i). Inhibition of endothelin-converting enzyme activity by
      phosphoramidon suppressed both the SFR and the increase in [Na(+)](i). The SFR
      and the increase in [Na(+)](i) after stretch were both present in muscles with
      their endothelium (vascular and endocardial) made functionally inactive by Triton
      X-100. In these muscles, phosphoramidon also suppressed the SFR and the increase
      in [Na(+)](i). The data provide evidence that the last step of the autocrine
      paracrine mechanism leading to the SFR to stretch is Ca(2+) entry through the
      reverse mode of Na(+)-Ca(2+) exchange.

PMID- 11230104
TI  - Comparison of two murine models of familial hypertrophic cardiomyopathy.
AB  - Although sarcomere protein gene mutations cause familial hypertrophic
      cardiomyopathy (FHC), individuals bearing a mutant cardiac myosin binding protein
      C (MyBP-C) gene usually have a better prognosis than individuals bearing beta
      cardiac myosin heavy chain (MHC) gene mutations. Heterozygous mice bearing a
      cardiac MHC missense mutation (alphaMHC(403/+) or a cardiac MyBP-C mutation (MyBP
      C(t/+)) were constructed as murine FHC models using homologous recombination in
      embryonic stem cells. We have compared cardiac structure and function of these
      mouse strains by several methods to further define mechanisms that determine the
      severity of FHC. Both strains demonstrated progressive left ventricular (LV)
      hypertrophy; however, by age 30 weeks, alphaMHC(403/+) mice demonstrated
      considerably more LV hypertrophy than MyBP-C(t/+) mice. In older heterozygous
      mice, hypertrophy continued to be more severe in the alphaMHC(403/+) mice than in
      the MyBP-C(t/+) mice. Consistent with this finding, hearts from 50-week-old
      alphaMHC(403/+) mice demonstrated increased expression of molecular markers of
      cardiac hypertrophy, but MyBP-C(t/+) hearts did not demonstrate expression of
      these molecular markers until the mice were >125 weeks old. Electrophysiological
      evaluation indicated that MyBP-C(t/+) mice are not as likely to have inducible
      ventricular tachycardia as alphaMHC(403/+) mice. In addition, cardiac function of
      alphaMHC(403/+) mice is significantly impaired before the development of LV
      hypertrophy, whereas cardiac function of MyBP-C(t/+) mice is not impaired even
      after the development of cardiac hypertrophy. Because these murine FHC models
      mimic their human counterparts, we propose that similar murine models will be
      useful for predicting the clinical consequences of other FHC-causing mutations.
      These data suggest that both electrophysiological and cardiac function studies
      may enable more definitive risk stratification in FHC patients.

PMID- 11230105
TI  - Absence of CD40 signaling is associated with an increase in intimal thickening
      after arterial injury.
AB  - Immune-mediator CD40 ligand is expressed on a variety of cell types involved in
      the immune response and on the cells of the vascular system. Inhibition of CD40
      signaling has been associated with reduction of experimental atherosclerosis and
      transplant-associated vasculopathy. Immune response also plays a cardinal role in
      intimal thickening after acute arterial-wall injury. After carotid artery injury
      in CD40 ligand knockout (CD40L(-/-)) mice, the intimal thickening was increased 3
      fold compared with the thickening in background B6/129 mice. The extent of
      thickening was similar to the thickening in B6/129 mice depleted of T lymphocytes
      with anti-CD4 and anti-CD8 antibodies. Injection of splenocytes from B6/129 mice
      into the CD40L(-/-) mice reduced the intimal thickening to the level comparable
      to the thickening in background B6/129 mice. These data suggest that CD40
      signaling plays a significant role in the inhibitory effect of T lymphocytes on
      intimal thickening after arterial injury.

PMID- 11230106
TI  - Development of the myocardium of the atrioventricular canal and the vestibular
      spine in the human heart.
AB  - To establish the morphogenetic mechanisms underlying formation and separation of
      the atrioventricular connections, we studied the remodeling of the myocardium of
      the atrioventricular canal and the extracardiac mesenchymal tissue of the
      vestibular spine in human embryonic hearts from 4.5 to 10 weeks of development.
      Septation of the atrioventricular junction is brought about by downgrowth of the
      primary atrial septum, fusion of the endocardial cushions, and forward expansion
      of the vestibular spine between atrial septum and cushions. The vestibular spine
      subsequently myocardializes to form the ventral rim of the oval fossa. The
      connection of the atrioventricular canal with the atria expands evenly. In
      contrast, the expression patterns of creatine kinase M and GlN2, markers for the
      atrioventricular and interventricular junctions, respectively, show that the
      junction of the canal with the right ventricle forms by local growth in the inner
      curvature of the heart. Growth of the caudal portion of the muscular ventricular
      septum to make contact with the inferior endocardial cushion occurs only after
      the canal has expanded rightward. The atrioventricular node develops from that
      part of the canal myocardium that retains its continuity with the ventricular
      myocardium.

PMID- 11230107
TI  - Identification of the t-type calcium channel (Ca(v)3.1d) in developing mouse
      heart.
AB  - During cardiac development, there is a reciprocal relationship between cardiac
      morphogenesis and force production (contractility). In the early embryonic
      myocardium, the sarcoplasmic reticulum is poorly developed, and plasma membrane
      calcium (Ca(2+)) channels are critical for maintaining both contractility and
      excitability. In the present study, we identified the Ca(V)3.1d mRNA expressed in
      embryonic day 14 (E14) mouse heart. Ca(V)3.1d is a splice variant of the alpha1G,
      T-type Ca(2+) channel. Immunohistochemical localization showed expression of
      alpha1G Ca(2+) channels in E14 myocardium, and staining of isolated ventricular
      myocytes revealed membrane localization of the alpha1G channels. Dihydropyridine
      resistant inward Ba(2+) or Ca(2+) currents were present in all fetal ventricular
      myocytes tested. Regardless of charge carrier, inward current inactivated with
      sustained depolarization and mirrored steady-state inactivation voltage
      dependence of the alpha1G channel expressed in human embryonic kidney-293 cells.
      Ni(2+) blockade discriminates among T-type Ca(2+) channel isoforms and is a
      relatively selective blocker of T-type channels over other cardiac plasma
      membrane Ca(2+) handling proteins. We demonstrate that 100 micromol/L Ni(2+)
      partially blocked alpha1G currents under physiological external Ca(2+). We
      conclude that alpha1G T-type Ca(2+) channels are functional in midgestational
      fetal myocardium.

PMID- 11230108
TI  - Cyclin A/cdk2 activation is involved in hypoxia-induced apoptosis in
      cardiomyocytes.
AB  - Cardiomyocytes are terminally differentiated cells characterized as withdrawal
      cell-cycle machinery, but nonetheless they are known to express cell-cycle
      regulators. Because many proteins related to the cell cycle induce apoptosis in
      proliferating cells, we examined the involvement of these proteins in the
      apoptosis pathway in cardiomyocytes. Primary rat cardiomyocytes were exposed to a
      severe hypoxic condition to induce apoptosis. The apoptosis rate of
      cardiomyocytes increased to approximately 40% under 24 hours of hypoxia as
      evaluated by the TUNEL method. The cyclin A protein level assessed by immunoblot
      analysis accumulated in a time-dependent manner in cardiomyocytes, but there was
      no increase in nonmyocytes. Hypoxia increased the activity of cyclin A-associated
      kinase but not the activity of cyclin E-associated kinase, and the apoptosis was
      inhibited by infection of dominant-negative cdk2 adenovirus, suggesting that
      cyclin A and its associated kinase play significant roles in the apoptosis of
      cardiomyocytes. To investigate the cyclin A-mediated apoptosis, we infected
      cultured cells with cyclin A adenovirus. Apoptosis was induced in 63+/-12% of the
      infected cardiomyocytes in contrast to only 12+/-3% of the LacZ-infected control
      cells. In addition, the cells in the hypoxic condition showed an increase in
      caspase-3 activity and a subsequent decrease in p21(cip1/waf1) protein, which is
      partly cleaved by caspase-3. These findings confirm that cyclin A-associated
      kinase mediates hypoxia-induced apoptosis in cardiomyocytes, and they also
      suggest that additional elements of the cell-cycle-dependent machinery
      participate in this mechanism.

PMID- 11230109
TI  - Tight control of exogenous SERCA expression is required to obtain acceleration of
      calcium transients with minimal cytotoxic effects in cardiac myocytes.
AB  - Collateral effects of exogenous sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA)
      expression were characterized in neonatal rat and chicken embryo cardiac
      myocytes, and the conditions required to produce acceleration of Ca(2+)
      transients with minimal toxicity were established. Cultured myocytes were
      infected with adenovirus vector carrying the cDNA of wild-type SERCA1, an
      inactive SERCA1 mutant, or enhanced green fluorescence protein under control of
      the cytomegalovirus promoter. Controls were exposed to empty virus vector. Each
      group was tested with and without phenylephrine (PHE) treatment. Under conditions
      of limited calf-serum exposure, the infected rat myocytes manifested a more rapid
      increase in size, protein content, and rate of protein synthesis relative to
      noninfected controls. These changes were not accompanied by reversal to fetal
      transcriptional pattern (as observed in hypertrophy triggered by PHE) and may be
      attributable to facilitated exchange with serum factors. SERCA virus titers >5 to
      6 plaque-forming units per cell produced overcrowding of ATPase molecules on
      intracellular membranes, followed by apoptotic death of a significant number of
      rat but not chicken myocytes. Enhanced green fluorescence protein virus and empty
      virus also produced cytotoxic effects but at higher titers than SERCA. Expression
      of exogenous SERCA and enhancement of Ca(2+) transient kinetics could be obtained
      with minimal cell damage in rat myocytes if the SERCA virus titer were maintained
      within 1 to 4 plaque-forming units per cell. Expression of endogenous SERCA was
      unchanged, but expression of exogenous SERCA was higher in myocytes rendered
      hypertrophic by treatment with PHE than in nontreated controls.

PMID- 11230110
TI  - Activation of human neutrophil by cytokine-activated endothelial cells.
AB  - Cytokine activation of vascular endothelial cells renders the hyperadhesiveness
      for neutrophils. During the processes of inflammation and atherosclerosis, the
      production of reactive oxygen species by neutrophils contributes to endothelial
      cell (EC) damage and injury. However, the precise mechanisms for neutrophil
      activation by ECs remain unknown. Thus, we investigated what kinds of
      pathophysiological factors synthesized by inflammatory cytokine-activated ECs
      potentiated the activity of neutrophil functions. The magnitude of O(2)(-)
      release from neutrophils, which is one of pivotal neutrophil functions, was
      measured as an indicator potentiated by activated ECs. Neutrophils release
      massive amounts of O(2)(-) on coculture with activated ECs. Anti-granulocyte
      macrophage colony-stimulating factor (GM-CSF) antibody (Ab) or specific platelet
      activating factor (PAF)-receptor antagonist suppressed the O(2)(-) release from
      neutrophils on coculture with the activated ECs by 50% to 70%. The supernatants
      from activated ECs also induced O(2)(-) release by neutrophils. This stimulatory
      effect of activated EC supernatants on O(2)(-) release by neutrophils was
      abolished by anti-GM-CSF Ab or by PAF-receptor antagonist. As we previously
      reported, we demonstrated the expression of GM-CSF mRNA by Northern blotting and
      protein synthesis of GM-CSF by ELISA on tumor necrosis factor as well as
      interleukin-1-activated ECs. Although phosphorylation of mitogen-activated
      protein kinases was observed in ECs stimulated by tumor necrosis factor and
      interleukin-1, treatment of ECs with PD98059 (MEK1 inhibitor) and SB203580 (p38
      mitogen-activated protein kinase inhibitor) in the presence of the cytokine
      failed to attenuate the stimulatory effect of activated ECs on neutrophil
      activation. We found that activated ECs regulated neutrophil function on
      coculture. We show here for the first time, to our knowledge, that the
      collaboration between GM-CSF and PAF synthesized by activated ECs markedly
      potentiated neutrophil activation.

PMID- 11230111
TI  - Antigraft antibody-mediated expression of metalloproteinases on endothelial
      cells. Differential expression of TIMP-1 and ADAM-10 depends on antibody
      specificity and isotype.
AB  - Endothelial cell (EC) interaction with antigraft antibodies (Abs) mediates EC
      injury and activation involved in vascular graft rejection. The aim of this study
      was to identify EC genes regulated in response to antigraft Ab binding that
      contribute to the endothelium alterations implicated in graft rejection or
      survival. By means of RNA differential display, 13 cDNA fragments corresponding
      to genes differentially expressed in ECs incubated with antigraft Abs were
      identified. Among these cDNAs were found the tissue inhibitor of
      metalloproteinase-1 (TIMP-1) and a desintegrin and metalloproteinase (ADAM-10).
      We demonstrated that TIMP-1 and ADAM-10 mRNA and protein expression was rapidly
      upregulated in ECs in response to antigraft Ab binding. Our data showed that TIMP
      1 was upregulated in response to human IgG but not IgM and anti-galactosyl (Gal)
      alpha1-3Gal human xenogeneic Abs. In contrast, upregulation of ADAM-10 in ECs was
      shown to be mostly mediated by anti-Galalpha1-3Gal IgM Abs. Specific effects of
      human IgG and IgM xenogeneic Abs on endothelial transcripts indicate that
      different isotypes and specificities of Abs may mediate different EC changes. Our
      results suggest that interaction of ECs with antigraft Abs, according to their
      specificity, selectively induces synthesis and release of metalloproteinases and
      inhibitors, controlling proteolytic processes and immunological events that
      respectively contribute to graft rejection or survival.

PMID- 11230112
TI  - Human platelets contain a glycosylated estrogen receptor beta.
AB  - Platelets play an important role in the coronary thrombus formation that leads to
      myocardial ischemia and infarction. Gender differences in the development of
      coronary heart disease and its outcomes are partly regulated by estrogen and its
      receptors, but the roles of the latter in thrombogenicity are less well-defined.
      We previously demonstrated the presence of estrogen receptor (ER) beta in cells
      of the megakaryocytic lineage. In this study, we characterize human platelet
      ERbeta and its expression using biochemical and molecular biological techniques.
      Western immunoblotting showed that platelet ERbeta migrated with an apparent
      molecular mass approximately 3.7 kDa larger than ERbeta in a variety of cell
      lines (including those of prostate and breast origin). A rigorous investigation
      of platelet ERbeta mRNA by reverse transcriptase-polymerase chain reaction
      revealed normal transcripts and a single alternately spliced mRNA. However, this
      variant form was smaller, lacking exon 2, and could not account for the larger
      protein size seen in platelets. Treatment of ERbeta with N-glycosidase F, which
      removes core carbohydrate residues, caused a more rapid migration through
      polyacrylamide gels but had no effect on ERbeta from human cell lines. We
      conclude that the larger form of ERbeta in human platelets is not attributable to
      alternate mRNA splicing but primarily to tissue-specific glycosylation.

PMID- 11230114
TI  - De Novo expression of macrophage migration inhibitory factor in atherogenesis.

PMID- 11230113
TI  - Cardiac-specific overexpression of cyclin-dependent kinase 2 increases smaller
      mononuclear cardiomyocytes.
AB  - Cyclin-dependent kinase 2 (cdk2) plays a critical role in the G1- to S-phase
      checkpoint of the cell cycle. Adult cardiomyocytes are believed to withdraw from
      the cell cycle. To determine whether forced overexpression of cdk2 results in
      altered cell-cycle regulation in the adult heart, we generated transgenic mice
      specifically overexpressing cdk2 in hearts. Transgenic hearts expressed high
      levels of both cdk2 mRNA and catalytically active cdk2 proteins. Cdk2
      overexpression significantly increased the levels of cdk4 and cyclins A, D3, and
      E. There was an increase in both DNA synthesis and proliferating cell nuclear
      antigen levels in the adult transgenic hearts. The ratio of heart weight to body
      weight in cdk2 transgenic mice was significantly increased in neonatal day 2 but
      not in adults compared with that of wild-type mice. Analysis of dispersed
      individual adult cardiomyocytes showed a 5.6-fold increase in the proportion of
      smaller mononuclear cardiomyocytes in the transgenic mice. Echocardiography
      revealed that transgenic heart was functionally normal. However, adult transgenic
      ventricles expressed beta-myosin heavy chain and atrial natriuretic factor.
      Surgically induced pressure overload caused an exaggerated maladaptive
      hypertrophic response in transgenic mice but did not change the proportion of
      mononuclear cardiomyocytes. The data suggest that overexpression of cdk2 promotes
      smaller, less-differentiated mononuclear cardiomyocytes in adult hearts that
      respond in an exaggerated manner to pressure overload.

PMID- 11230115
TI  - Modulation of Ca(2+) signaling by microtubule disruption in rat ventricular
      myocytes and its dependence on the ruptured patch-clamp configuration.
AB  - In the absence of hypertrophic proliferation of microtubules, microtubule
      disruption by colchicine does not modulate contraction of adult cardiac myocytes.
      However, Gomez et al (Circ Res. 2000;86:30-36) recently reported that disruption
      of microtubules by colchicine in ruptured patch-clamped myocytes increased
      I(Ca,L) density and [Ca(2+)](i) transient amplitude and depressed the response of
      these parameters to the beta-adrenoceptor agonist isoproterenol. These effects
      were ascribed to stimulation of adenylyl cyclase by increased intracellular free
      tubulin. In the present study, we show that in intact rat ventricular myocytes, 2
      to 4 hours of exposure to 10 micromol/L colchicine had no effect on shortening or
      [Ca(2+)](i) transient amplitude or on the amplitude of I(Ca,L) in perforated
      patch-clamped cells, under basal conditions and after stimulation with 1
      micromol/L isoproterenol. However, in ruptured patch-clamped myocytes, basal
      I(Ca,L) was 2-fold higher after treatment with colchicine compared with vehicle
      and, in contrast to vehicle-treated cells, I(Ca,L) did not increase in response
      to isoproterenol. Cell width decreased during ruptured patch-clamp experiments in
      colchicine-treated but not vehicle-treated myocytes. We conclude that in cells
      with intact sarcolemma, colchicine does not modulate Ca(2+) signaling or the
      response to beta stimulation. However, the combination of microtubule disruption
      by colchicine and the ruptured patch configuration activates I(Ca,L) and
      attenuates the response to beta stimulation. We propose that these effects may be
      due to loss of free tubulin by intracellular dialysis or to increased sensitivity
      to mechanical stimulation as a result of microtubule disruption. These findings
      have important implications for cardiomyopathies associated with decreased free
      tubulin or a diminished microtubular network. The full text of this article is
      available at http://www.circresaha.org.

PMID- 11230116
TI  - Retinoids induce fibroblast growth factor-2 production in endothelial cells via
      retinoic acid receptor alpha activation and stimulate angiogenesis in vitro and
      in vivo.
AB  - The effect of retinoic acid (RA) on endothelial cells is still controversial and
      was examined in the present study. In bovine aortic endothelial cells (BAECs),
      all-trans RA (ATRA) and 9-cis RA (9CRA), but not 13-cis RA (13CRA), induced
      fibroblast growth factor-2 (FGF-2) production and exhibited a biphasic dose
      dependent effect to enhance BAEC proliferation and differentiation into tubular
      structures on reconstituted basement membrane proteins (Matrigel); both processes
      were inhibited by FGF-2-neutralizing antibody. The pan RA receptor (RAR)
      selective ligand (E)-4-[2-(5,5,8,8,-tetramethyl-5,6,7,8-tetrahydro-2-naphtalenyl)
      1-propenyl] benzoic acid and the RARalpha-selective ligand 4-[1-(3,5,5,8,8
      pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)-ethenyl] benzoic acid stimulated the
      production of FGF-2, whereas the addition of the RARalpha-antagonist RO 41-5253
      inhibited this effect. In BAECs, the forced expression of RARalpha, but not
      RARbeta or RARgamma, enhanced FGF-2 production, whereas the RARalpha-dominant
      negative, Delta403, blocked this effect. Furthermore, RARalpha overexpression
      directly stimulated BAEC differentiation on Matrigel and potentiated the effects
      of ATRA in this assay. Finally, ATRA-treated BAECs coinjected with Matrigel
      subcutaneously in mice induced neovascularization within the Matrigel plug, and
      ATRA also enhanced angiogenesis in the chicken chorioallantoic membrane assay. In
      conclusion, RA can stimulate endothelial cell proliferation and differentiation
      in vitro via enhanced RARalpha-dependent FGF-2 production, and it can also induce
      angiogenesis in vivo. The full text of this article is available at
      http://www.circresaha.org.

PMID- 11230117
TI  - Ion channels in the outer membranes of chloroplasts and mitochondria: open doors
      or regulated gates?

PMID- 11230118
TI  - The mitochondrial Hsp70-dependent import system actively unfolds preproteins and
      shortens the lag phase of translocation.
AB  - Unfolding is an essential process during translocation of preproteins into
      mitochondria; however, controversy exists as to whether mitochondria play an
      active role in unfolding. We have established an in vitro system with a kinetic
      saturation of the mitochondrial import machinery, yielding translocation rates
      comparable to in vivo import rates. Preproteins with short N-terminal segments in
      front of a folded domain show a characteristic delay of the onset of
      translocation (lag phase) although the maximal import rate is similar to that of
      longer preproteins. The lag phase is shortened by extending the N-terminal
      segment to improve the accessibility to matrix heat shock protein 70 and
      abolished by unfolding of the preprotein. A mutant mtHsp70 defective in binding
      to the inner membrane prolongs the lag phase and reduces the translocation
      activity. A direct comparison of the rate of spontaneous unfolding in solution
      with that during translocation demonstrates that unfolding by mitochondria is
      significantly faster, proving an active unfolding process. We conclude that
      access of mtHsp70 to N-terminal preprotein segments is critical for active
      unfolding and initiation of translocation.

PMID- 11230119
TI  - The three modules of ADP/ATP carrier cooperate in receptor recruitment and
      translocation into mitochondria.
AB  - The ADP/ATP carrier (AAC) is a major representative of mitochondrial preproteins
      lacking an N-terminal presequence. AAC contains targeting information in each of
      its three modules, which has led to a search for the dominant targeting region.
      An alternative, not yet tested model would be that several distinct targeting
      signals function simultaneously in import of the preprotein. We report that the
      three AAC modules cooperate in binding to the receptor Tom70 such that three
      Tom70 dimers are recruited to one preprotein. The modules are transferred to the
      import pore in a stepwise manner and cooperate again in the accumulation of AAC
      in the general import pore complex. AAC can cross the outer membrane with an
      internal segment first, i.e. in a loop formation. Each module of AAC is required
      for dimerization in the inner membrane. We propose a new concept for import of
      the hydrophobic carrier proteins into mitochondria where multiple signals
      cooperate in receptor recruitment, outer membrane translocation via loop
      formation and assembly in the inner membrane.

PMID- 11230120
TI  - Cross-talk between catalytic and regulatory elements in a DEAD motor domain is
      essential for SecA function.
AB  - SecA, the motor subunit of bacterial polypeptide translocase, is an RNA helicase.
      SecA comprises a dimerization C-terminal domain fused to an ATPase N-terminal
      domain containing conserved DEAD helicase motifs. We show that the N-terminal
      domain is organized like the motor core of DEAD proteins, encompassing two
      subdomains, NBD1 and IRA2. NBD1, a rigid nucleotide-binding domain, contains the
      minimal ATPase catalytic machinery. IRA2 binds to NBD1 and acts as an
      intramolecular regulator of ATP hydrolysis by controlling ADP release and optimal
      ATP catalysis at NBD1. IRA2 is flexible and can undergo changes in its alpha
      helical content. The C-terminal domain associates with NBD1 and IRA2 and
      restricts IRA2 activator function. Thus, cytoplasmic SecA is maintained in the
      thermally stabilized ADP-bound state and unnecessary ATP hydrolysis cycles are
      prevented. Two DEAD family motifs in IRA2 are essential for IRA2-NBD1 binding,
      optimal nucleotide turnover and polypeptide translocation. We propose that
      translocation ligands alleviate C-terminal domain suppression, allowing IRA2 to
      stimulate nucleotide turnover at NBD1. DEAD motors may employ similar mechanisms
      to translocate different enzymes along chemically unrelated biopolymers.

PMID- 11230121
TI  - Crystal structure of outer surface protein C (OspC) from the Lyme disease
      spirochete, Borrelia burgdorferi.
AB  - Outer surface protein C (OspC) is a major antigen on the surface of the Lyme
      disease spirochete, Borrelia burgdorferi, when it is being transmitted to humans.
      Crystal structures of OspC have been determined for strains HB19 and B31 to 1.8
      and 2.5 A resolution, respectively. The three-dimensional structure is
      predominantly helical. This is in contrast to the structure of OspA, a major
      surface protein mainly present when spirochetes are residing in the midgut of
      unfed ticks, which is mostly beta-sheet. The surface of OspC that would project
      away from the spirochete's membrane has a region of strong negative electrostatic
      potential which may be involved in binding to positively charged host ligands.
      This feature is present only on OspCs from strains known to cause invasive human
      disease.

PMID- 11230122
TI  - Structure of the reovirus outer capsid and dsRNA-binding protein sigma3 at 1.8 A
      resolution.
AB  - The crystallographically determined structure of the reovirus outer capsid
      protein sigma3 reveals a two-lobed structure organized around a long central
      helix. The smaller of the two lobes includes a CCHC zinc-binding site. Residues
      that vary between strains and serotypes lie mainly on one surface of the protein;
      residues on the opposite surface are conserved. From a fit of this model to a
      reconstruction of the whole virion from electron cryomicroscopy, we propose that
      each sigma3 subunit is positioned with the small lobe anchoring it to the protein
      mu1 on the surface of the virion, and the large lobe, the site of initial
      cleavages during entry-related proteolytic disassembly, protruding outwards. The
      surface containing variable residues faces solvent. The crystallographic
      asymmetric unit contains two sigma3 subunits, tightly associated as a dimer. One
      broad surface of the dimer has a positively charged surface patch, which extends
      across the dyad. In infected cells, sigma3 binds dsRNA and inhibits the
      interferon response. The location and extent of the positively charged surface
      patch suggest that the dimer is the RNA-binding form of sigma3.

PMID- 11230123
TI  - Crystal structure of the Lrp-like transcriptional regulator from the archaeon
      Pyrococcus furiosus.
AB  - The LrpA protein from the hyperthermophilic archaeon Pyrococcus furiosus belongs
      to the Lrp/AsnC family of transcriptional regulatory proteins, of which the
      Escherichia coli leucine-responsive regulatory protein is the archetype. Its
      crystal structure has been determined at 2.9 A resolution and is the first for a
      member of the Lrp/AsnC family, as well as one of the first for a transcriptional
      regulator from a hyperthermophile. The structure consists of an N-terminal domain
      containing a helix-turn-helix (HtH) DNA-binding motif, and a C-terminal domain of
      mixed alpha/beta character reminiscent of a number of RNA- and DNA-binding
      domains. Pyrococcus furiosus LrpA forms a homodimer mainly through interactions
      between the antiparallel beta-sheets of the C-terminal domain, and further
      interactions lead to octamer formation. The LrpA structure suggests how the
      protein might bind and possibly distort its DNA substrate through use of its HtH
      motifs and control gene expression. A possible location for an effector binding
      site is proposed by using sequence comparisons with other members of the family
      coupled to mutational analysis.

PMID- 11230124
TI  - Recruitment, activation and retention of caspases-9 and -3 by Apaf-1 apoptosome
      and associated XIAP complexes.
AB  - During apoptosis, release of cytochrome c initiates dATP-dependent
      oligomerization of Apaf-1 and formation of the apoptosome. In a cell-free system,
      we have addressed the order in which apical and effector caspases, caspases-9 and
      -3, respectively, are recruited to, activated and retained within the apoptosome.
      We propose a multi-step process, whereby catalytically active processed or
      unprocessed caspase-9 initially binds the Apaf-1 apoptosome in cytochrome c/dATP
      activated lysates and consequently recruits caspase-3 via an interaction between
      the active site cysteine (C287) in caspase-9 and a critical aspartate (D175) in
      caspase-3. We demonstrate that XIAP, an inhibitor-of-apoptosis protein, is
      normally present in high molecular weight complexes in unactivated cell lysates,
      but directly interacts with the apoptosome in cytochrome c/dATP-activated
      lysates. XIAP associates with oligomerized Apaf-1 and/or processed caspase-9 and
      influences the activation of caspase-3, but also binds activated caspase-3
      produced within the apoptosome and sequesters it within the complex. Thus, XIAP
      may regulate cell death by inhibiting the activation of caspase-3 within the
      apoptosome and by preventing release of active caspase-3 from the complex.

PMID- 11230125
TI  - Arabidopsis glucosidase I mutants reveal a critical role of N-glycan trimming in
      seed development.
AB  - Glycoproteins with asparagine-linked (N-linked) glycans occur in all eukaryotic
      cells. The function of their glycan moieties is one of the central problems in
      contemporary cell biology. N-glycosylation may modify physicochemical and
      biological protein properties such as conformation, degradation, intracellular
      sorting or secretion. We have isolated and characterized two allelic Arabidopsis
      mutants, gcs1-1 and gcs1-2, which produce abnormal shrunken seeds, blocked at the
      heart stage of development. The mutant seeds accumulate a low level of storage
      proteins, have no typical protein bodies, display abnormal cell enlargement and
      show occasional cell wall disruptions. The mutated gene has been cloned by T-DNA
      tagging. It codes for a protein homologous to animal and yeast alpha-glucosidase
      I, an enzyme that controls the first committed step for N-glycan trimming.
      Biochemical analyses have confirmed that trimming of the alpha1,2- linked
      glucosyl residue constitutive of the N-glycan precursor is blocked in this
      mutant. These results demonstrate the importance of N-glycan trimming for the
      accumulation of seed storage proteins, the formation of protein bodies, cell
      differentiation and embryo development.

PMID- 11230126
TI  - Calcineurin is required for hyphal elongation during mating and haploid fruiting
      in Cryptococcus neoformans.
AB  - Cryptococcus neoformans is a fungal pathogen that causes meningitis in
      immunocompromised patients. Its growth is sensitive to the immunosuppressants
      FK506 and cyclosporin, which inhibit the Ca2+- calmodulin-activated protein
      phosphatase calcineurin. Calcineurin is required for growth at 37 degrees C and
      virulence of C.neoformans. We found that calcineurin is also required for mating.
      FK506 blocks mating of C.neoformans via FKBP12-dependent inhibition of
      calcineurin, and mutants lacking calcineurin are bilaterally sterile. Calcineurin
      is not essential for the initial fusion event, but is required for hyphal
      elongation and survival of the heterokaryon produced by cell fusion. It is also
      required for hyphal elongation in diploid strains and during asexual haploid
      fruiting of MATalpha cells in response to nitrogen limitation. Because mating and
      haploid fruiting produce infectious basidiospores, our studies suggest a second
      link between calcineurin and virulence of C.neoformans. Calcine urin regulates
      filamentation and 37 degrees C growth via distinct pathways. Together with
      studies revealing that calcineurin mediates neurite extension and neutrophil
      migration in mammals, our findings indicate that calcineurin plays a conserved
      role in the control of cell morphology.

PMID- 11230127
TI  - Reversible inhibition of Hsp70 chaperone function by Scythe and Reaper.
AB  - Protein folding mediated by the Hsp70 family of molecular chaperones requires
      both ATP and the co-chaperone Hdj-1. BAG-1 was recently identified as a bcl-2
      interacting, anti-apoptotic protein that binds to the ATPase domain of Hsp70 and
      prevents the release of the substrate. While this suggested that cells had the
      potential to modulate Hsp70-mediated protein folding, physiological regulators of
      BAG-1 have yet to be identified. We report here that the apoptotic regulator
      Scythe, originally isolated through binding to the potent apoptotic inducer
      Reaper, shares limited sequence identity with BAG-1 and inhibits Hsp70- mediated
      protein refolding. Scythe-mediated inhibition of Hsp70 is reversed by Reaper,
      providing evidence for the regulated reversible inhibition of chaperone activity.
      As Scythe functions downstream of Reaper in apoptotic induction, these findings
      suggest that Scythe/Reaper may signal apoptosis, in part through regulating the
      folding and activity of apoptotic signaling molecules.

PMID- 11230128
TI  - Its substrate specificity characterizes the DnaJ co-chaperone as a scanning
      factor for the DnaK chaperone.
AB  - The evolutionarily conserved DnaJ proteins are essential components of Hsp70
      chaperone systems. The DnaJ homologue of Escherichia coli associates with
      chaperone substrates and mediates their ATP hydrolysis-dependent locking into the
      binding cavity of its Hsp70 partner, DnaK. To determine the substrate specificity
      of DnaJ proteins, we screened 1633 peptides derived from 14 protein sequences for
      binding to E.coli DnaJ. The binding motif of DnaJ consists of a hydrophobic core
      of approximately eight residues enriched for aromatic and large aliphatic
      hydrophobic residues and arginine. The hydrophobicity of this motif explains why
      DnaJ itself can prevent protein aggregation. Although this motif shows
      differences from DnaK's binding motif, DnaJ and DnaK share the majority of
      binding peptides. In contrast to DnaK, DnaJ binds peptides consisting of L- and D
      amino acids, and therefore is not restricted by backbone contacts. These features
      allow DnaJ to scan hydrophobic protein surfaces and initiate the functional cycle
      of the DnaK system by associating with hydrophobic exposed patches and subsequent
      targeting of DnaK to these or to hydrophobic patches in spatial neighbourhood.

PMID- 11230129
TI  - The NAF domain defines a novel protein-protein interaction module conserved in
      Ca2+-regulated kinases.
AB  - The Arabidopsis calcineurin B-like calcium sensor proteins (AtCBLs) interact with
      a group of serine-threonine protein kinases (AtCIPKs) in a calcium-dependent
      manner. Here we identify a 24 amino acid domain (NAF domain) unique to these
      kinases as being required and sufficient for interaction with all known AtCBLs.
      Mutation of conserved residues either abolished or significantly diminished the
      affinity of AtCIPK1 for AtCBL2. Comprehensive two-hybrid screens with various
      AtCBLs identified 15 CIPKs as potential targets of CBL proteins. Database
      analyses revealed additional kinases from Arabidopsis and other plant species
      harbouring the NAF interaction module. Several of these kinases have been
      implicated in various signalling pathways mediating responses to stress, hormones
      and environmental cues. Full-length CIPKs show preferential interaction with
      distinct CBLs in yeast and in vitro assays. Our findings suggest differential
      interaction affinity as one of the mechanisms generating the temporal and spatial
      specificity of calcium signals within plant cells and that different combinations
      of CBL-CIPK proteins contribute to the complex network that connects various
      extracellular signals to defined cellular responses.

PMID- 11230130
TI  - Fission yeast Pom1p kinase activity is cell cycle regulated and essential for
      cellular symmetry during growth and division.
AB  - Schizosaccharomyces pombe cells grow from both ends during most of interphase and
      divide symmetrically into two daughter cells. The pom1 gene, encoding a member of
      the Dyrk family of protein kinases, has been identified through a mutant showing
      abnormal cellular morphogenesis. Here we show that Pom1p kinase activity is cell
      cycle regulated in correlation with the state of cellular symmetry: the activity
      is high during symmetrical growth and division, but lower when cells grow at just
      one end. Point mutations in the catalytic domain lead to asymmetry during both
      cell growth and division, whilst cells overexpressing Pom1p form additional
      growing ends. Manipulations of kinase activity indicate a negative role for Pom1p
      in microtubule growth at cell ends. Pom1p is present in a large protein complex
      and requires its non-catalytic domain to localize to the cell periphery and its
      kinase activity to localize to cell ends. These data establish that Pom1p kinase
      activity plays an important role in generating cellular symmetry and suggest that
      there may be related roles of homologous protein kinases ubiquitously present in
      all eukaryotes.

PMID- 11230131
TI  - GSK-3 kinase Mck1 and calcineurin coordinately mediate Hsl1 down-regulation by
      Ca2+ in budding yeast.
AB  - The Ca2+-activated pathways of Saccharomyces cerevisiae induce a delay in the
      onset of mitosis through the activation of Swe1, a negative regulatory kinase
      that inhibits the Cdc28-Clb complex. Calcineurin and Mpk1 activate Swe1 at the
      transcriptional and post-translational level, respectively, and both pathways are
      essential for the cell cycle delay. Our genetic screening identified the MCK1
      gene, which encodes a glycogen synthetase kinase-3 family protein kinase, as a
      component of the Ca2+ signaling pathway. Genetic analyses indicated that Mck1
      functions downstream of the Mpk1 pathway and down-regulates Hsl1, an inhibitory
      kinase of Swe1. In medium with a high concentration of Ca2+, Hsl1 was delocalized
      from the bud neck and destabilized in a manner dependent on both calcineurin and
      Mck1. Calcineurin was required for the dephosphorylation of autophosphorylated
      Hsl1. The E3 ubiquitin ligase complex SCF(Cdc4), but not the anaphase-promoting
      complex (APC), was essential for Hsl1 destabilization. The Ca2+-activated pathway
      may play a role in the rapid inactivation of Hsl1 at the cell cycle stage(s) when
      APC activity is low.

PMID- 11230132
TI  - The human cytomegalovirus immediate early 2 protein dissociates cellular DNA
      synthesis from cyclin-dependent kinase activation.
AB  - Passage through the restriction point late in G1 normally commits cells to
      replicate their DNA. Here we show that the previously reported cell cycle block
      mediated by the human cytomegalovirus (HCMV) immediate early 2 (IE2) protein
      uncouples this association. First, IE2 expression leads to elevated levels of
      cyclin E-associated kinase activity via transcriptional activation of the cyclin
      E gene. This contributes to post-restriction point characteristics of IE2
      expressing cells. Then these cells fail to undergo substantial DNA replication
      although they have entered S phase, and the induction of DNA replication observed
      after overexpression of cyclin E or D can be antagonized by IE2 without impinging
      on cyclin-associated kinase activities. These data suggest that IE2 secures
      restriction-point transition of cells before it stops them from replicating their
      genome. Our results fit well with HCMV physiology and support the view that IE2
      is part of a viral activity which, on the one hand, promotes cell cycle-dependent
      expression of cellular replication factors but, on the other hand, disallows
      competitive cellular DNA synthesis.

PMID- 11230133
TI  - Autophosphorylation restrains the apoptotic activity of DRP-1 kinase by
      controlling dimerization and calmodulin binding.
AB  - DRP-1 is a pro-apoptotic Ca2+/calmodulin (CaM)-regulated serine/threonine kinase,
      recently isolated as a novel member of the DAP-kinase family of proteins. It
      contains a short extra-catalytic tail required for homodimerization. Here we
      identify a novel regulatory mechanism that controls its pro-apoptotic functions.
      It comprises a single autophosphorylation event mapped to Ser308 within the CaM
      regulatory domain. A negative charge at this site reduces both the binding to CaM
      and the formation of DRP-1 homodimers. Conversely, the dephosphorylation of
      Ser308, which takes place in response to activated Fas or tumour necrosis factor
      alpha death receptors, increases the formation of DRP-1 dimers, facilitates the
      binding to CaM and activates the pro-apoptotic effects of the protein. Thus, the
      process of enzyme activation is controlled by two unlocking steps that must work
      in concert, i.e. dephosphorylation, which probably weakens the electrostatic
      interactions between the CaM regulatory domain and the catalytic cleft, and
      homodimerization. This mechanism of negative autophosphorylation provides a
      safety barrier that restrains the killing effects of DRP-1, and a target for
      efficient activation of the kinase by various apoptotic stimuli.

PMID- 11230135
TI  - Regulation of the Sko1 transcriptional repressor by the Hog1 MAP kinase in
      response to osmotic stress.
AB  - Exposure of yeast to increases in extracellular osmolarity activates the Hog1
      mitogen-activated protein kinase (MAPK), which is essential for the induction of
      gene expression required for cell survival upon osmotic stress. Several genes are
      regulated in response to osmotic stress by Sko1, a transcriptional repressor of
      the ATF/CREB family. We show by in vivo coprecipitation and phosphorylation
      studies that Sko1 and Hog1 interact and that Sko1 is phosphorylated upon osmotic
      stress in a Hog1-dependent manner. Hog1 phosphorylates Sko1 in vitro at multiple
      sites within the N-terminal region. Phosphorylation of Sko1 disrupts the Sko1
      Ssn6-Tup1 repressor complex, and consistently, a mutant allele of Sko1,
      unphosphorylatable by Hog1, exhibits less derepression than the wild type.
      Interestingly, Sko1 repressor activity is further enhanced in strains with high
      protein kinase A (PKA) activity. PKA phosphorylates Sko1 near the bZIP domain and
      mutation of these sites eliminates modulation of Sko1 responses to high PKA
      activity. Thus, Sko1 transcriptional repression is controlled directly by the
      Hog1 MAPK in response to stress, and this effect is further modulated by an
      independent signaling mechanism through the PKA pathway.

PMID- 11230134
TI  - The transcription factors MTF-1 and USF1 cooperate to regulate mouse
      metallothionein-I expression in response to the essential metal zinc in visceral
      endoderm cells during early development.
AB  - During early development of the mouse embryo, expression of the metallothionein-I
      (MT-I) gene is heightened specifically in the endoderm cells of the visceral yolk
      sac. The mechanisms of regulation of this cell-specific pattern of expression of
      metallothionein-I are unknown. However, it has recently been shown that MTF-1,
      functioning as a metalloregulatory transcription factor, activates
      metallothionein genes in response to the essential metal zinc. In contrast with
      the metallothionein genes, MTF-1 is essential for development; null mutant
      embryos die due to liver degeneration. We report here that MTF-1 is absolutely
      essential for upregulation of MT-I gene expression in visceral endoderm cells and
      that optimal expression also involves interactions of the basic helix-loop-helix
      upstream stimulatory factor-1 (USF1) with an E-box1-containing sequence at -223
      bp in the MT-I promoter. Expression of MT-I in visceral endoderm cells was
      dependent on maternal dietary zinc. Thus, the essential metal, zinc, apparently
      provides the signaling ligand that activates cell-specific MT-I expression in
      visceral endoderm cells.

PMID- 11230136
TI  - A novel mRNA-decapping activity in HeLa cytoplasmic extracts is regulated by AU
      rich elements.
AB  - While decapping plays a major role in mRNA turnover in yeast, biochemical
      evidence for a similar activity in mammalian cells has been elusive. We have now
      identified a decapping activity in HeLa cytoplasmic extracts that releases
      (7me)GDP from capped transcripts. Decapping is activated in extracts by the
      addition of (7me)GpppG, which specifically sequesters cap-binding proteins such
      as eIF4E and the deadenylase DAN/PARN. Similar to in vivo observations, the
      presence of a poly(A) tail represses decapping of RNAs in vitro in a poly(A)
      binding protein-dependent fashion. AU-rich elements (AREs), which act as
      regulators of mRNA stability in vivo, are potent stimulators of decapping in
      vitro. The stimulation of decapping by AREs requires sequence-specific ARE
      binding proteins. These data suggest that cap recognition and decapping play key
      roles in mediating mRNA turnover in mammalian cells.

PMID- 11230138
TI  - Oligomeric structures of poliovirus polymerase are important for function.
AB  - Central to the replication of poliovirus and other positive-strand RNA viruses is
      the virally encoded RNA-dependent RNA polymerase. Previous biochemical studies
      have suggested that direct polymerase- polymerase interactions might be important
      for polymerase function, and the structure of poliovirus polymerase has revealed
      two regions of extensive polymerase-polymerase interaction. To explore potential
      functional roles for the structurally observed polymerase-polymerase
      interactions, we have performed RNA binding and extension studies of mutant
      polymerase proteins in solution, disulfide cross-linking studies, mutational
      analyses in cells, in vitro activity analyses and RNA substrate modeling studies.
      The results of these studies indicate that both regions of polymerase-polymerase
      interaction observed in the crystals are indeed functionally important and,
      furthermore, reveal specific functional roles for each. One of the two regions of
      interaction provides for efficient substrate RNA binding and the second is
      crucial for forming catalytic sites. These studies strongly support the
      hypothesis that the polymerase- polymerase interactions discovered in the crystal
      structure provide an exquisitely detailed structural context for poliovirus
      polymerase function and for poliovirus RNA replication in cells.

PMID- 11230137
TI  - Involvement of a site-specific trans-acting factor and a common RNA-binding
      protein in the editing of chloroplast mRNAs: development of a chloroplast in
      vitro RNA editing system.
AB  - RNA editing in higher plant chloroplasts involves C-->U conversion at
      approximately 30 specific sites. An in vitro system supporting accurate editing
      has been developed from tobacco chloroplasts. Mutational analysis of substrate
      mRNAs derived from tobacco chloroplast psbL and ndhB mRNAs confirmed the
      participation of cis-acting elements that had previously been identified in vivo.
      Competition analysis revealed the existence of site-specific trans-acting factors
      interacting with the corresponding upstream cis-elements. A chloroplast protein
      of 25 kDa was found to be specifically associated with the cis-element involved
      in psbL mRNA editing. Immunological analyses revealed that an additional factor,
      the chloroplast RNA-binding protein cp31, is also required for RNA editing at
      multiple sites. This combination of site-specific and common RNA-binding proteins
      recognizes editing sites in chloroplasts.

PMID- 11230139
TI  - Mutations in DnaA protein suppress the growth arrest of acidic phospholipid
      deficient Escherichia coli cells.
AB  - Cell growth arrests when the concentrations of anionic phospholipids drop below a
      critical level in Escherichia coli, with the insufficient amounts of acidic
      phospholipids adversely affecting the DnaA-dependent initiation of DNA
      replication at the chromosomal origin (oriC). Mutations have been introduced into
      the carboxyl region of DnaA, including the portion identified as essential for
      productive in vitro DnaA-acidic phospholipid interactions. Expression of DnaA
      proteins possessing certain small deletions or substituted amino acids restored
      growth to cells deficient in acidic phospholipids, whereas expression of wild
      type DnaA did not. The mutations include substitutions and deletions in the
      phospholipid-interacting domain as well as some small deletions in the DNA
      binding domain of DnaA. Marker frequency analysis indicated that initiation of
      replication occurs at or near oriC in acidic phospholipid- deficient cells
      rescued by the expression of DnaA having a point mutation in the membrane-binding
      domain, DnaA(L366K). Flow cytometry revealed that expression in wild-type cells
      of plasmid-borne DnaA(L366K) and DnaA(Delta363-367) reduced the frequency with
      which replication was initiated and disturbed the synchrony of initiations.

PMID- 11230140
TI  - Ten1 functions in telomere end protection and length regulation in association
      with Stn1 and Cdc13.
AB  - In Saccharomyces cerevisiae, Cdc13 has been proposed to mediate telomerase
      recruitment at telomere ends. Stn1, which associates with Cdc13 by the two-hybrid
      interaction, has been implicated in telomere maintenance. Ten1, a previously
      uncharacterized protein, was found to associate physically with both Stn1 and
      Cdc13. A binding defect between Stn1-13 and Ten1 was responsible for the long
      telomere phenotype of stn1-13 mutant cells. Moreover, rescue of the cdc13-1
      mutation by STN1 was much improved when TEN1 was simultaneously overexpressed.
      Several ten1 mutations were found to confer telomerase-dependent telomere
      lengthening. Other, temperature-sensitive, mutants of TEN1 arrested at G(2)/M via
      activation of the Rad9-dependent DNA damage checkpoint. These ten1 mutant cells
      were found to accumulate single-stranded DNA in telomeric regions of the
      chromosomes. We propose that Ten1 is required to regulate telomere length, as
      well as to prevent lethal damage to telomeric DNA.

PMID- 11230141
TI  - Regulated phase transitions of bacterial chromatin: a non-enzymatic pathway for
      generic DNA protection.
AB  - The enhanced stress resistance exhibited by starved bacteria represents a central
      facet of virulence, since nutrient depletion is regularly encountered by
      pathogens in their natural in vivo and ex vivo environments. Here we explore the
      notion that the regular stress responses, which are mediated by enzymatically
      catalyzed chemical transactions and promote endurance during the logarithmic
      growth phase, can no longer be effectively induced during starvation. We show
      that survival of bacteria in nutrient-depleted habitats is promoted by a novel
      strategy: finely tuned and fully reversible intracellular phase transitions.
      These non-enzymatic transactions, detected and studied in bacteria as well as in
      defined in vitro systems, result in DNA sequestration and generic protection
      within tightly packed and highly ordered assemblies. Since this physical mode of
      defense is uniquely independent of enzymatic activity or de novo protein
      synthesis, and consequently does not require energy consumption, it promotes
      virulence by enabling long-term bacterial endurance and enhancing antibiotic
      resistance in adverse habitats.

PMID- 11230142
TI  - Physical interactions between DinI and RecA nucleoprotein filament for the
      regulation of SOS mutagenesis.
AB  - The Escherichia coli dinI gene is one of the LexA-regulated genes, which are
      induced upon DNA damage. Its overexpression conferred severe UV sensitivity on
      wild-type cells and resulted in the inhibition of LexA and UmuD processing,
      reactions that are normally dependent on activated RecA in a complex with single
      stranded (ss)DNA. Here, we study the mechanism by which DinI inhibits the
      activities of RecA. While DinI neither binds to ssDNA nor prevents the formation
      of RecA nucleoprotein filament, it binds to active RecA filament, thereby
      inhibiting its coprotease activity but not the ATPase activity. Furthermore, even
      under in vitro conditions where UmuD cleavage dependent on RecA-ssDNA-adeno sine
      5'-(3-thiotriphosphate) is blocked in the presence of DinI, LexA is cleaved
      normally. This result, taken together with electron microscopy observations and
      linear dichroism measurements, indicates that the ternary complex remains intact
      in the presence of DinI, and that the affinity to the RecA filament decreases in
      the order LexA, DinI and UmuD. DinI is thus suited to modulating UmuD processing
      so as to limit SOS mutagenesis.

PMID- 11230143
TI  - The small DNA binding domain of lambda integrase is a context-sensitive modulator
      of recombinase functions.
AB  - lambda Integrase (Int) has the distinctive ability to bridge two different and
      well separated DNA sequences. This heterobivalent DNA binding is facilitated by
      accessory DNA bending proteins that bring flanking Int sites into proximity. The
      regulation of lambda recombination has long been perceived as a structural
      phenomenon based upon the accessory protein-dependent Int bridges between high
      affinity arm-type (bound by the small N-terminal domain) and low-affinity core
      type DNA sites (bound by the large C-terminal domain). We show here that the N
      terminal domain is not merely a guide for the proper positioning of Int
      protomers, but is also a context-sensitive modulator of recombinase functions. In
      full-length Int, it inhibits C-terminal domain binding and cleavage at the core
      sites. Surprisingly, its presence as a separate molecule stimulates the C
      terminal domain functions. The inhibition in full-length Int is reversed or
      overcome in the presence of arm-type oligonucleotides, which form specific
      complexes with Int and core-type DNA. We consider how these results might
      influence models and experiments pertaining to the large family of heterobivalent
      recombinases.

PMID- 11230144
TI  - Temporal and spatial regulation of Rho-type guanine-nucleotide exchange factors:
      the yeast perspective.

PMID- 11230145
TI  - Activation of the Notch-regulated transcription factor CBF1/RBP-Jkappa through
      the 13SE1A oncoprotein.
AB  - Signaling through the Notch pathway controls cell growth and differentiation in
      metazoans. Following binding of its ligands, the intracellular part of the cell
      surface Notch1 receptor (Notch1-IC) is released and translocates to the nucleus,
      where it alters the function of the DNA-binding transcription factor CBF1/RBP
      Jkappa. As a result, CBF1/RBP-Jkappa is converted from a repressor to an
      activator of gene transcription. Similarly, the Epstein Barr viral oncoprotein
      EBNA2, which is required for B-cell immortalization, activates genes through
      CBF1. Moreover, the TAN-1 and int-3 oncogenes represent activated versions of
      Notch1 and Notch4, respectively. Here, we show that the adenoviral oncoprotein
      13S E1A also binds to CBF1/RBP-Jkappa, displaces associated corepressor
      complexes, and activates CBF1/RBP-Jkappa-dependent gene expression. Our results
      suggest that the central role of the Notch-CBF1/RBP-Jkappa signaling pathway in
      cell fate decisions renders it susceptible to pathways of viral replication and
      oncogenic conversion.

PMID- 11230146
TI  - E2F3 contributes both to the inappropriate proliferation and to the apoptosis
      arising in Rb mutant embryos.
AB  - The E2F transcription factors are thought to be key downstream targets of the
      retinoblastoma protein (pRB) tumor suppressor. It is widely believed that E2F1,
      E2F2, and E2F3 can all activate cellular proliferation but that E2F1 is the
      specific inducer of apoptosis. Here we show that the E2f3 mutation completely
      suppresses both the inappropriate proliferation and the p53-dependent apoptosis
      arising in the Rb mutant embryos. Through the analysis of Rb(-/-);E2f3(+/-)
      embryos, we have been able to separate E2F3's role in the induction of apoptosis
      from its ability to induce proliferation. Thus, contrary to the prevailing view
      of E2F action, E2F3 makes a major contribution to the apoptosis resulting from
      pRB loss.

PMID- 11230147
TI  - Active repression and E2F inhibition by pRB are biochemically distinguishable.
AB  - To understand mechanistically how pRB represses transcription, we used a
      reconstituted transcription assay and compared pRB activity on naked versus
      chromatin templates. Surprisingly, when pRB was directly recruited to a naked
      template, no transcriptional repression was observed. However, we observed active
      repression when the same promoter was assembled into chromatin. Histone
      deacetylases do not appear to play a role in this observed repression. Further
      experiments showed repression could occur after preinitiation complex assembly,
      in contrast with pRB inhibition of E2F, suggesting discrete mechanisms by which
      pRB directly inhibits an activator such as E2F or actively represses proximally
      bound transcription factors.

PMID- 11230148
TI  - Putative telomere-independent mechanisms of replicative aging reflect inadequate
      growth conditions.
AB  - Telomere shortening is the mechanism underlying replicative aging in fibroblasts.
      A variety of reports now claim that inactivation of the p16(INK4a)/pRB pathway is
      required in addition to telomere maintenance for the immortalization of cells
      such as skin keratinocytes and breast epithelial cells. We here show that the
      premature growth arrest of these cell types can be explained by an inadequate
      culture environment. Providing mesenchymal/epithelial interactions by cultivating
      the telomerase-expressing cells on feeder layers avoids the growth arrest
      associated with increased p16(INK4a). These results do not support a telomere
      independent mechanism of replicative aging.

PMID- 11230149
TI  - Cdc13 both positively and negatively regulates telomere replication.
AB  - Cdc13 is a single-strand telomeric DNA-binding protein that positively regulates
      yeast telomere replication by recruiting telomerase to chromosome termini through
      a site on Cdc13 that is eliminated by the cdc13-2 mutation. Here we show that
      Cdc13 has a separate role in negative regulation of telomere replication, based
      on analysis of a new mutation, cdc13-5. Loss of this second regulatory activity
      results in extensive elongation of the G strand of the telomere by telomerase,
      accompanied by a reduced ability to coordinate synthesis of the C strand. Both
      the cdc13-5 mutation and DNA polymerase alpha mutations (which also exhibit
      elongated telomeres) are suppressed by increased expression of the Cdc13
      interacting protein Stn1, indicating that Stn1 coordinates action of the lagging
      strand replication complex with the regulatory activity of CDC13. However, the
      association between Cdc13 and Stn1 is abolished by cdc13-2, the same mutation
      that eliminates the interaction between Cdc13 and telomerase. We propose that
      Cdc13 participates in two regulatory steps-first positive, then negative-as a
      result of successive binding of telomerase and the negative regulator Stn1 to
      overlapping sites on Cdc13. Thus, Cdc13 coordinates synthesis of both strands of
      the telomere by first recruiting telomerase and subsequently limiting G-strand
      synthesis by telomerase in response to C-strand replication.

PMID- 11230150
TI  - A model for the abrogation of the SOS response by an SOS protein: a negatively
      charged helix in DinI mimics DNA in its interaction with RecA.
AB  - DinI is a recently described negative regulator of the SOS response in
      Escherichia coli. Here we show that it physically interacts with RecA and
      prevents the binding of single-stranded DNA to RecA, which is required for the
      activation of the latter. DinI also displaces ssDNA from a stable RecA-DNA
      cofilament, thus eliminating the SOS signal. In addition, DinI inhibits RecA
      mediated homologous DNA pairing, but has no effect on actively proceeding strand
      exchange. Biochemical data, together with the molecular structure, define the C
      terminal alpha-helix in DinI as the active site of the protein. In an unusual
      example of molecular mimicry, a negatively charged surface on this alpha-helix,
      by imitating single-stranded DNA, interacts with the loop L2 homologous pairing
      region of RecA and interferes with the activation of RecA.

PMID- 11230151
TI  - Targeting histone deacetylase complexes via KRAB-zinc finger proteins: the PHD
      and bromodomains of KAP-1 form a cooperative unit that recruits a novel isoform
      of the Mi-2alpha subunit of NuRD.
AB  - Macromolecular complexes containing histone deacetylase and ATPase activities
      regulate chromatin dynamics and are vitally responsible for transcriptional gene
      silencing in eukaryotes. The mechanisms that target these assemblies to specific
      loci are not as well understood. We show that the corepressor KAP-1, via its PHD
      (plant homeodomain) and bromodomain, links the superfamily of Kruppel associated
      box (KRAB) zinc finger proteins (ZFP) to the NuRD complex. We demonstrate that
      the tandem PHD finger and bromodomain of KAP-1, an arrangement often found in
      cofactor proteins but functionally ill-defined, form a cooperative unit that is
      required for transcriptional repression. Substitution of highly related PHD
      fingers or bromodomains failed to restore repression activity, suggesting high
      specificity in their cooperative function. Moreover, single amino acid
      substitutions in either the bromodomain or PHD finger, including ones that mimic
      disease-causing mutations in the hATRX PHD finger, abolish repression. A search
      for effectors of this repression function yielded a novel isoform of the Mi
      2alpha protein, an integral component of the NuRD complex. Endogenous KAP-1 is
      associated with Mi-2alpha and other components of NuRD, and KAP-1-mediated
      silencing requires association with NuRD and HDAC activity. These data suggest
      the KRAB-ZFP superfamily of repressors functions to target the histone
      deacetylase and chromatin remodeling activities of the NuRD complex to specific
      gene promoters in vivo.

PMID- 11230152
TI  - Key events of pancreas formation are triggered in gut endoderm by ectopic
      expression of pancreatic regulatory genes.
AB  - The mechanisms by which the epithelium of the digestive tract and its associated
      glands are specified are largely unknown. One clue is that several transcription
      factors are expressed in specific regions of the endoderm prior to and during
      organogenesis. Pdx-1, for example, is expressed in the duodenum and pancreas and
      Pdx-1 inactivation results in an arrest of pancreatic development after buds
      formation. Similarly, ngn3 is transiently expressed in the developing pancreas
      and a knockout results in the absence of endocrine cells. This paper focuses on
      the question of whether these and other transcription factors, known to be
      necessary for pancreatic development, are also sufficient to drive a program of
      pancreatic organogenesis. Using in ovo electroporation of chick embryos, we show
      that ectopic expression of Pdx-1 or ngn3 causes cells to bud out of the
      epithelium like pancreatic progenitors. The Pdx-1-expressing cells extinguish
      markers for other nonpancreatic regions of the endoderm and initiate, but do not
      complete, pancreatic cytodifferentiation. Ectopic expression of ngn3 is
      sufficient to turn endodermal cells of any region into endocrine cells that form
      islets expressing glucagon and somatostatin in the mesenchyme. The results
      suggest that simple gene combinations could be used in stem cells to achieve
      specific endodermal tissue differentiation.

PMID- 11230153
TI  - The hepatitis B virus encoded oncoprotein pX amplifies TGF-beta family signaling
      through direct interaction with Smad4: potential mechanism of hepatitis B virus
      induced liver fibrosis.
AB  - Hepatitis B, one of the most common infectious diseases in the world, is closely
      associated with acute and chronic hepatitis, cirrhosis, and hepatocellular
      carcinoma. Many clinical investigations have revealed that hepatic fibrosis is an
      important component of these liver diseases caused by chronic hepatitis B. TGF
      beta signaling plays an important role in the pathogenesis of fibrosis in chronic
      hepatitis and cirrhosis. As these diseases are associated with hepatitis B virus
      (HBV) infection, we examined the possibility that the HBV-encoded pX oncoprotein
      regulates TGF-beta signaling. We show that pX enhances transcriptional activity
      in response to TGF-beta, BMP-2, and activin by stabilizing the complex of Smad4
      with components of the basic transcriptional machinery. Additionally, confocal
      microscopic studies suggest that pX facilitates and potentiates the nuclear
      translocation of Smads, further enhancing TGF-beta signaling. Our studies suggest
      a new paradigm for amplification of Smad-mediated signaling by an oncoprotein and
      suggest that enhanced Smad-mediated signaling may contribute to HBV-associated
      liver fibrosis.

PMID- 11230154
TI  - Continuous expression of Cbfa1 in nonhypertrophic chondrocytes uncovers its
      ability to induce hypertrophic chondrocyte differentiation and partially rescues
      Cbfa1-deficient mice.
AB  - Chondrocyte hypertrophy is a mandatory step during endochondral ossification.
      Cbfa1-deficient mice lack hypertrophic chondrocytes in some skeletal elements,
      indicating that Cbfa1 may control hypertrophic chondrocyte differentiation. To
      address this question we generated transgenic mice expressing Cbfa1 in
      nonhypertrophic chondrocytes (alpha1(II) Cbfa1). This continuous expression of
      Cbfa1 in nonhypertrophic chondrocytes induced chondrocyte hypertrophy and
      endochondral ossification in locations where it normally never occurs. To
      determine if this was caused by transdifferentiation of chondrocytes into
      osteoblasts or by a specific hypertrophic chondrocyte differentiation ability of
      Cbfa1, we used the alpha1(II) Cbfa1 transgene to restore Cbfa1 expression in
      mesenchymal condensations of the Cbfa1-deficient mice. The transgene restored
      chondrocyte hypertrophy and vascular invasion in the bones of the mutant mice but
      did not induce osteoblast differentiation. This rescue occurred cell
      autonomously, as skeletal elements not expressing the transgene were not
      affected. Despite the absence of osteoblasts in the rescued animals there were
      multinucleated, TRAP-positive cells resorbing the hypertrophic cartilage matrix.
      These results identify Cbfa1 as a hypertrophic chondrocyte differentiation factor
      and provide a genetic argument for a common regulation of osteoblast and
      chondrocyte differentiation mediated by Cbfa1.

PMID- 11230155
TI  - Life with 25,000 genes.

PMID- 11230156
TI  - Genomics in Latin America: reaching the frontiers.

PMID- 11230157
TI  - Using mouse genetics to understand infectious disease pathogenesis.

PMID- 11230158
TI  - First pass annotation of promoters on human chromosome 22.
AB  - The publication of the first almost complete sequence of a human chromosome
      (chromosome 22) is a major milestone in human genomics. Together with the
      sequence, an excellent annotation of genes was published which certainly will
      serve as an information resource for numerous future projects. We noted that the
      annotation did not cover regulatory regions; in particular, no promoter
      annotation has been provided. Here we present an analysis of the complete
      published chromosome 22 sequence for promoters. A recent breakthrough in specific
      in silico prediction of promoter regions enabled us to attempt large-scale
      prediction of promoter regions on chromosome 22. Scanning of sequence databases
      revealed only 20 experimentally verified promoters, of which 10 were correctly
      predicted by our approach. Nearly 40% of our 465 predicted promoter regions are
      supported by the currently available gene annotation. Promoter finding also
      provides a biologically meaningful method for "chromosomal scaffolding", by which
      long genomic sequences can be divided into segments starting with a gene. As one
      example, the combination of promoter region prediction with exon/intron structure
      predictions greatly enhances the specificity of de novo gene finding. The present
      study demonstrates that it is possible to identify promoters in silico on the
      chromosomal level with sufficient reliability for experimental planning and
      indicates that a wealth of information about regulatory regions can be extracted
      from current large-scale (megabase) sequencing projects. Results are available on
      line at http://genomatix.gsf.de/chr22/.

PMID- 11230160
TI  - Genome alignment, evolution of prokaryotic genome organization, and prediction of
      gene function using genomic context.
AB  - Gene order in prokaryotes is conserved to a much lesser extent than protein
      sequences. Only several operons, primarily those that code for physically
      interacting proteins, are conserved in all or most of the bacterial and archaeal
      genomes. Nevertheless, even the limited conservation of operon organization that
      is observed can provide valuable evolutionary and functional clues through
      multiple genome comparisons. A program for constructing gapped local alignments
      of conserved gene strings in two genomes was developed. The statistical
      significance of the local alignments was assessed using Monte Carlo simulations.
      Sets of local alignments were generated for all pairs of completely sequenced
      bacterial and archaeal genomes, and for each genome a template-anchored multiple
      alignment was constructed. In most pairwise genome comparisons, <10% of the genes
      in each genome belonged to conserved gene strings. When closely related pairs of
      species (i.e., two mycoplasmas) are excluded, the total coverage of genomes by
      conserved gene strings ranged from <5% for the cyanobacterium Synechocystis sp to
      24% for the minimal genome of Mycoplasma genitalium, and 23% in Thermotoga
      maritima. The coverage of the archaeal genomes was only slightly lower than that
      of bacterial genomes. The majority of the conserved gene strings are known
      operons, with the ribosomal superoperon being the top-scoring string in most
      genome comparisons. However, in some of the bacterial-archaeal pairs, the
      superoperon is rearranged to the extent that other operons, primarily those
      subject to horizontal transfer, show the greatest level of conservation, such as
      the archaeal-type H+-ATPase operon or ABC-type transport cassettes. The level of
      gene order conservation among prokaryotic genomes was compared to the
      cooccurrence of genomes in clusters of orthologous genes (COGs) and to the
      conservation of protein sequences themselves. Only limited correlation was
      observed between these evolutionary variables. Gene order conservation shows a
      much lower variance than the cooccurrence of genomes in COGs, which indicates
      that intragenome homogenization via recombination occurs in evolution much faster
      than intergenome homogenization via horizontal gene transfer and lineage-specific
      gene loss. The potential of using template-anchored multiple-genome alignments
      for predicting functions of uncharacterized genes was quantitatively assessed.
      Functions were predicted or significantly clarified for approximately 90 COGs
      (approximately 4% of the total of 2414 analyzed COGs). The most significant
      predictions were obtained for the poorly characterized archaeal genomes; these
      include a previously uncharacterized restriction-modification system, a nuclease
      helicase combination implicated in DNA repair, and the probable archaeal
      counterpart of the eukaryotic exosome. Multiple genome alignments are a resource
      for studies on operon rearrangement and disruption, which is central to our
      understanding of the evolution of prokaryotic genomes. Because of the rapid
      evolution of the gene order, the potential of genome alignment for prediction of
      gene functions is limited, but nevertheless, such predictions information
      significantly complements the results obtained through protein sequence and
      structure analysis.

PMID- 11230161
TI  - Gene duplication and the structure of eukaryotic genomes.
AB  - A simple method for understanding how gene duplication has contributed to genomic
      structure was applied to the complete genomes of Caenorhabditis elegans,
      Drosophila melanogaster, and yeast Saccharomyces cerevisiae. By this method, the
      genes belonging to gene families (the paranome) were identified, and the extent
      of sharing of two or more families between genomic windows was compared with that
      expected under a null model. The results showed significant evidence of
      duplication of genomic blocks in both C. elegans and yeast. In C. elegans, the
      five block duplications identified all occurred intra-chromosomally, and all but
      one occurred quite recently. In yeast, by contrast, 39 duplicated blocks were
      identified, and all but one of these was inter-chromosomal. Of these 39 blocks,
      28 showed evidence of ancient duplication, possibly as a result of an ancient
      polyploidization event. By contrast, three blocks showed evidence of very recent
      duplication, while seven others showed a mixture of ancient and recent
      duplication events. Thus, duplication of genomic blocks has been an ongoing
      feature of yeast evolution over the past 200--300 million years.

PMID- 11230159
TI  - Identification of human epidermal differentiation complex (EDC)-encoded genes by
      subtractive hybridization of entire YACs to a gridded keratinocyte cDNA library.
AB  - The epidermal differentiation complex (EDC) comprises a large number of genes
      that are of crucial importance for the maturation of the human epidermis. So far,
      27 genes of 3 related families encoding structural as well as regulatory proteins
      have been mapped within a 2-Mb region on chromosome 1q21. Here we report on the
      identification of 10 additional EDC genes by a powerful subtractive hybridization
      method using entire YACs (950_e_2 and 986_e_10) to screen a gridded human
      keratinocyte cDNA library. Localization of the detected cDNA clones has been
      established on a long-range restriction map covering more than 5 Mb of this
      genomic region. The genes encode cytoskeletal tropomyosin TM30nm (TPM3), HS1
      binding protein Hax-1 (HAX1), RNA-specific adenosine deaminase (ADAR1), the 34/67
      kD laminin receptor (LAMRL6), and the 26S proteasome subunit p31 (PSMD8L), as
      well as five hitherto uncharacterized proteins (NICE-1, NICE-2, NICE-3, NICE-4,
      and NICE-5). The nucleotide sequences and putative ORFs of the EDC genes
      identified here revealed no homology with any of the established EDC gene
      families. Whereas database searches revealed that NICE-3, NICE-4, and NICE-5 were
      expressed in many tissues, no EST or gene-specific sequence was found for NICE-2.
      Expression of NICE-1 was up-regulated in differentiated keratinocytes, pointing
      to its relevance for the terminal differentiation of the epidermis. The newly
      identified EDC genes are likely to provide further insights into epidermal
      differentiation and they are potential candidates to be involved in skin diseases
      and carcinogenesis that are associated with this region of chromosome 1.
      Moreover, the extended integrated map of the EDC, including the polymorphic
      sequence tag site (STS) markers D1S1664, D1S2346, and D1S305, will serve as a
      valuable tool for linkage analyses.

PMID- 11230162
TI  - A dominant modifier of transgene methylation is mapped by QTL analysis to mouse
      chromosome 13.
AB  - The single-copy hepatitis B virus transgene in the E36 transgenic mouse strain
      undergoes methylation changes in a parent-of-origin, tissue, and strain-specific
      fashion. In a C57BL/6 background, the paternally transmitted transgene is
      methylated in 30% of cells, whereas it is methylated in more than 80% of cells in
      (BALB/c x C57BL/6) F1 mice. We established previously that several genetic
      factors were likely to contribute to the transgene methylation profile, some with
      demethylating and some with de novo methylating activities. Using quantitative
      trait loci (QTL) mapping, we have now localized one major modifier locus on
      chromosome 13 (Mod13), which explains a 30% increase in the methylation level of
      this transgene with no effect on the flanking endogenous sequences. No other QTL
      could be identified, except for a demethylating activity of low significance
      located on chromosome 12. Recombinant inbred mice containing a BALB/c allele of
      Mod13 were then used to show that the presence of Mod13 is sufficient to induce
      de novo methylation. A segregation between de novo methylation and repression of
      transgene expression was uncovered, suggesting that this genetic system is also
      useful for the identification of factors that interpret methylation patterns in
      the genome.

PMID- 11230163
TI  - Comparative DNA sequence analysis of mouse and human protocadherin gene clusters.
AB  - The genomic organization of the human protocadherin alpha, beta, and gamma gene
      clusters (designated Pcdh alpha [gene symbol PCDHA], Pcdh beta [PCDHB], and Pcdh
      gamma [PCDHG]) is remarkably similar to that of immunoglobulin and T-cell
      receptor genes. The extracellular and transmembrane domains of each protocadherin
      protein are encoded by an unusually large "variable" region exon, while the
      intracellular domains are encoded by three small "constant" region exons located
      downstream from a tandem array of variable region exons. Here we report the
      results of a comparative DNA sequence analysis of the orthologous human (750 kb)
      and mouse (900 kb) protocadherin gene clusters. The organization of Pcdh alpha
      and Pcdh gamma gene clusters in the two species is virtually identical, whereas
      the mouse Pcdh beta gene cluster is larger and contains more genes than the human
      Pcdh beta gene cluster. We identified conserved DNA sequences upstream of the
      variable region exons, and found that these sequences are more conserved between
      orthologs than between paralogs. Within this region, there is a highly conserved
      DNA sequence motif located at about the same position upstream of the translation
      start codon of each variable region exon. In addition, the variable region of
      each gene cluster contains a rich array of CpG islands, whose location
      corresponds to the position of each variable region exon. These observations are
      consistent with the proposal that the expression of each variable region exon is
      regulated by a distinct promoter, which is highly conserved between orthologous
      variable region exons in mouse and human.

PMID- 11230164
TI  - Microchip module for blood sample preparation and nucleic acid amplification
      reactions.
AB  - A computer numerical control-machined plexiglas-based microchip module was
      designed and constructed for the integration of blood sample preparation and
      nucleic acid amplification reactions. The microchip module is comprised of a
      custom-made heater-cooler for thermal cycling, a series of 254 microm x 254
      microm microchannels for transporting human whole blood and reagents in and out
      of an 8--9 microL dual-purpose (cell isolation and PCR) glass-silicon microchip.
      White blood cells were first isolated from a small volume of human whole blood
      (<3 microL) in an integrated cell isolation--PCR microchip containing a series of
      3.5-microm feature-sized "weir-type" filters, formed by an etched silicon dam
      spanning the flow chamber. A genomic target, a region in the human coagulation
      Factor V gene (226-bp), was subsequently directly amplified by microchip-based
      PCR on DNA released from white blood cells isolated on the filter section of the
      microchip mounted onto the microchip module. The microchip module provides a
      convenient means to simplify nucleic acid analyses by integrating two key steps
      in genetic testing procedures, cell isolation and PCR and promises to be
      adaptable for additional types of integrated assays.

PMID- 11230165
TI  - High-performance multiplex SNP analysis of three hemochromatosis-related
      mutations with capillary array electrophoresis microplates.
AB  - An assay is described for high-throughput single nucleotide polymorphism (SNP)
      genotyping on a microfabricated capillary array electrophoresis (CAE) microchip.
      The assay targets the three common variants at the HFE locus associated with the
      genetic disease hereditary hemochromatosis (HHC). The assay employs allele
      specific PCR (ASPCR) for the C282Y (845g->a), H63D (187c->g), and S65C (193a->t)
      variants using fluorescently-labeled energy-transfer (ET) allele-specific
      primers. Using a 96-channel radial CAE microplate, the labeled ASPCR products
      generated from 96 samples in a reference Caucasian population are simultaneously
      separated with single-base-pair resolution and genotyped in under 10 min.
      Detection is accomplished with a laser-excited rotary four-color fluorescence
      scanner. The allele-specific amplicons are differentiated on the basis of both
      their size and the color of the label emission. This study is the first
      demonstration of the combined use of ASPCR with ET primers and microfabricated
      radial CAE microplates to perform multiplex SNP analyses in a clinically relevant
      population.

PMID- 11230167
TI  - Fluorescence polarization in homogeneous nucleic acid analysis II: 5'-nuclease
      assay.
AB  - When the temperature and viscosity of the solvent is held constant, the degree of
      fluorescence polarization (FP) detected when a fluorescent dye is excited by
      plane polarized light depends mostly on the molecular weight of the dye molecule.
      By monitoring the FP of a fluorescent dye molecule, one can detect significant
      changes in the molecular weight of a fluorescent molecule without separation or
      purification. The 5'-nuclease (TaqMan) assay is a robust single nucleotide
      polymorphism genotyping method where an allele-specific probe that binds to a
      perfectly complementary target is cleaved by the 5'-nuclease activity of Taq DNA
      polymerase. Because the TaqMan probe is labeled with a fluorescent dye, it has
      high FP value when intact but a low FP value after cleavage. In this study, we
      compared the results of the 5'-nuclease assay based on standard fluorescence
      intensity readings and FP readings when genotyping 90 individuals with 20 single
      nucleotide polymorphisms. Our results show that FP is just as robust and reliable
      as the standard fluorescence detection method. Use of FP detection makes it
      possible to reduce the cost of TaqMan probes by abrogating the need for a
      fluorescence quencher.

PMID- 11230166
TI  - Toward a catalog of human genes and proteins: sequencing and analysis of 500
      novel complete protein coding human cDNAs.
AB  - With the complete human genomic sequence being unraveled, the focus will shift to
      gene identification and to the functional analysis of gene products. The
      generation of a set of cDNAs, both sequences and physical clones, which contains
      the complete and noninterrupted protein coding regions of all human genes will
      provide the indispensable tools for the systematic and comprehensive analysis of
      protein function to eventually understand the molecular basis of man. Here we
      report the sequencing and analysis of 500 novel human cDNAs containing the
      complete protein coding frame. Assignment to functional categories was possible
      for 52% (259) of the encoded proteins, the remaining fraction having no
      similarities with known proteins. By aligning the cDNA sequences with the
      sequences of the finished chromosomes 21 and 22 we identified a number of genes
      that either had been completely missed in the analysis of the genomic sequences
      or had been wrongly predicted. Three of these genes appear to be present in
      several copies. We conclude that full-length cDNA sequencing continues to be
      crucial also for the accurate identification of genes. The set of 500 novel
      cDNAs, and another 1000 full-coding cDNAs of known transcripts we have
      identified, adds up to cDNA representations covering 2%--5 % of all human genes.
      We thus substantially contribute to the generation of a gene catalog, consisting
      of both full-coding cDNA sequences and clones, which should be made freely
      available and will become an invaluable tool for detailed functional studies.

PMID- 11230168
TI  - A method for parallel, automated, thermal cycling of submicroliter samples.
AB  - A large fraction of the cost of DNA sequencing and other DNA-analysis processes
      results from the reagent costs incurred during cycle sequencing or PCR. In
      particular, the high cost of the enzymes and dyes used in these processes often
      results in thermal cycling costs exceeding $0.50 per sample. In the case of high
      throughput DNA sequencing, this is a significant and unnecessary expense.
      Improved detection efficiency of new sequencing instrumentation allows the
      reaction volumes for cycle sequencing to be scaled down to one-tenth of presently
      used volumes, resulting in at least a 10-fold decrease in the cost of this
      process. However, commercially available thermal cyclers and automated reaction
      setup devices have inherent design limitations which make handling volumes of <1
      microL extremely difficult. In this paper, we describe a method for thermal
      cycling aimed at reliable, automated cycling of submicroliter reaction volumes.

PMID- 11230170
TI  - A combinatorial partitioning method to identify multilocus genotypic partitions
      that predict quantitative trait variation.
AB  - Recent advances in genome research have accelerated the process of locating
      candidate genes and the variable sites within them and have simplified the task
      of genotype measurement. The development of statistical and computational
      strategies to utilize information on hundreds -- soon thousands -- of variable
      loci to investigate the relationships between genome variation and phenotypic
      variation has not kept pace, particularly for quantitative traits that do not
      follow simple Mendelian patterns of inheritance. We present here the
      combinatorial partitioning method (CPM) that examines multiple genes, each
      containing multiple variable loci, to identify partitions of multilocus genotypes
      that predict interindividual variation in quantitative trait levels. We
      illustrate this method with an application to plasma triglyceride levels
      collected on 188 males, ages 20--60 yr, ascertained without regard to health
      status, from Rochester, Minnesota. Genotype information included measurements at
      18 diallelic loci in six coronary heart disease--candidate susceptibility gene
      regions: APOA1--C3--A4, APOB, APOE, LDLR, LPL, and PON1. To illustrate the CPM,
      we evaluated all possible partitions of two-locus genotypes into two to nine
      partitions (approximately 10(6) evaluations). We found that many combinations of
      loci are involved in sets of genotypic partitions that predict triglyceride
      variability and that the most predictive sets show nonadditivity. These results
      suggest that traditional methods of building multilocus models that rely on
      statistically significant marginal, single-locus effects, may fail to identify
      combinations of loci that best predict trait variability. The CPM offers a
      strategy for exploring the high-dimensional genotype state space so as to predict
      the quantitative trait variation in the population at large that does not require
      the conditioning of the analysis on a prespecified genetic model.

PMID- 11230169
TI  - A novel chromatin immunoprecipitation and array (CIA) analysis identifies a 460
      kb CENP-A-binding neocentromere DNA.
AB  - Centromere protein A (CENP-A) is an essential histone H3-related protein that
      constitutes the specialized chromatin of an active centromere. It has been
      suggested that this protein plays a key role in the epigenetic marking and
      transformation of noncentromeric genomic DNA into functional neocentromeres.
      Neocentromeres have been identified on more than two-thirds of the human
      chromosomes, presumably involving different noncentromeric DNA sequences, but it
      is unclear whether some generalized sequence properties account for these
      neocentromeric sites. Using a novel method combining chromatin
      immunoprecipitation and genomic array hybridization, we have identified a 460-kb
      CENP-A-binding DNA domain of a neocentromere derived from the 20p12 region of an
      invdup (20p) human marker chromosome. Detailed sequence analysis indicates that
      this domain contains no centromeric alpha-satellite, classical satellites, or
      other known pericentric repetitive sequence motifs. Putative gene loci are
      detected, suggesting that their presence does not preclude neocentromere
      formation. The sequence is not significantly different from surrounding non-CENP
      A-binding DNA in terms of the prevalence of various interspersed repeats and
      binding sites for DNA-interacting proteins (Topoisomerase II and High-Mobility
      Group protein I). Notable variations include a higher AT content similar to that
      seen in human alpha-satellite DNA and a reduced prevalence of long terminal
      repeats (LTRs), short interspersed repeats (SINEs), and Alus. The significance of
      these features in neocentromerization is discussed.

PMID- 11230171
TI  - Y-chromosomal SNPs in Finno-Ugric-speaking populations analyzed by minisequencing
      on microarrays.
AB  - An increasing number of single nucleotide polymorphisms (SNPs) on the Y
      chromosome are being identified. To utilize the full potential of the SNP markers
      in population genetic studies, new genotyping methods with high throughput are
      required. We describe a microarray system based on the minisequencing single
      nucleotide primer extension principle for multiplex genotyping of Y-chromosomal
      SNP markers. The system was applied for screening a panel of 25 Y-chromosomal
      SNPs in a unique collection of samples representing five Finno--Ugric
      populations. The specific minisequencing reaction provides 5-fold to infinite
      discrimination between the Y-chromosomal genotypes, and the microarray format of
      the system allows parallel and simultaneous analysis of large numbers of SNPs and
      samples. In addition to the SNP markers, five Y-chromosomal microsatellite loci
      were typed. Altogether 10,000 genotypes were generated to assess the genetic
      diversity in these population samples. Six of the 25 SNP markers (M9, Tat,
      SRY10831, M17, M12, 92R7) were polymorphic in the analyzed populations, yielding
      six distinct SNP haplotypes. The microsatellite data were used to study the
      genetic structure of two major SNP haplotypes in the Finns and the Saami in more
      detail. We found that the most common haplotypes are shared between the Finns and
      the Saami, and that the SNP haplotypes show regional differences within the Finns
      and the Saami, which supports the hypothesis of two separate settlement waves to
      Finland.

PMID- 11230173
TI  - Generation of a high-density rat EST map.
AB  - We have developed a high-density EST map of the rat, consisting of >11,000 ESTs.
      These ESTs were placed on a radiation hybrid framework map of genetic markers
      spanning all 20 rat autosomes, plus the X chromosome. The framework maps have a
      total size of approximately 12,400 cR, giving an average correspondence of 240
      kb/cR. The frameworks are all LOD 3 chromosomal maps consisting of 775 radiation
      hybrid-mapped genetic markers and ESTs. To date, we have generated radiation
      hybrid-mapping data for >14,000 novel ESTs identified by our Rat Gene Discovery
      and Mapping Project (http://ratEST.uiowa.edu), from which we have placed >11,000
      on our framework maps. To minimize mapping errors, ESTs were mapped in duplicate
      and consensus RH vectors produced for use in the placement procedure. This EST
      map was then used to construct high-density comparative maps between rat and
      human and rat and mouse. These maps will be a useful resource for positional
      cloning of genes for rat models of human diseases and in the creation and
      verification of a tiling set of map order for the upcoming rat-genome sequencing.

PMID- 11230175
TI  - Rats made congenic for Oia3 on chromosome 10 become susceptible to squalene
      induced arthritis.
AB  - Several quantitative trait loci (QTLs) regulating the risk of experimental
      arthritis have been identified by genome-wide linkage analyses, but only the MHC
      has thus far been reported to transfer arthritis susceptibility in congenic
      animals. We have produced a congenic strain for Oia3, a genetic factor originally
      identified as an oil-induced arthritis (OIA) QTL in arthritis-prone DA rats. A 46
      cM telomeric region of chromosome 10 encompassing Oia3 was transferred from DA
      rats to MHC-identical but minutely arthritis-susceptible LEW.1AV1 rats by
      selective breeding. Arthritis development was provoked in Oia3-congenic rats by
      intradermal injection of different adjuvant oils. One successful arthritis
      trigger was squalene, which is approved for vaccinations in humans and has been
      implicated in Gulf War syndrome. The endogenous cholesterol precursor squalene
      induced T cell infiltration into joints and macroscopic arthritis in Oia3
      congenic rats and DA rats, whereas LEW.1AV1 rats were almost resistant. Arthritis
      onset, approximately 14 days post-injection, coincided with arrested body-weight
      gain and increased plasma levels of the inflammation markers fibrinogen and alpha
      1-acid glycoprotein. Congenic rats displayed intermediate phenotypes compared
      with the two parental strains, and similar to rheumatoid arthritis in humans,
      female preponderance was observed in Oia3-congenic rats. Finally, recombinant rat
      strains were constructed and were used to map a susceptibility gene(s) in females
      to a telomeric 4--19 cM Oia3 subregion. The experimental system described allows
      transformation of multifactorial arthritis susceptibility into dichotomous
      phenotypes.

PMID- 11230174
TI  - Biochemical, phenotypic and neurophysiological characterization of a genetic
      mouse model of RSH/Smith--Lemli--Opitz syndrome.
AB  - The RSH/Smith--Lemli--Opitz syndrome (RSH/SLOS) is a human autosomal recessive
      syndrome characterized by multiple malformations, a distinct behavioral phenotype
      with autistic features and mental retardation. RSH/SLOS is due to an inborn error
      of cholesterol biosynthesis caused by mutation of the 3 beta-hydroxysterol
      Delta(7)-reductase gene. To further our understanding of the developmental and
      neurological processes that underlie the pathophysiology of this disorder, we
      have developed a mouse model of RSH/SLOS by disruption of the 3 beta
      hydroxysterol Delta(7)-reductase gene. Here we provide the biochemical,
      phenotypic and neurophysiological characterization of this genetic mouse model.
      As in human patients, the RSH/SLOS mouse has a marked reduction of serum and
      tissue cholesterol levels and a marked increase of serum and tissue 7
      dehydrocholesterol levels. Phenotypic similarities between this mouse model and
      the human syndrome include intra-uterine growth retardation, variable
      craniofacial anomalies including cleft palate, poor feeding with an uncoordinated
      suck, hypotonia and decreased movement. Neurophysiological studies showed that
      although the response of frontal cortex neurons to the neurotransmitter gamma
      amino-n-butyric acid was normal, the response of these same neurons to glutamate
      was significantly impaired. This finding provides insight into potential
      mechanisms underlying the neurological dysfunction seen in this human mental
      retardation syndrome and suggests that this mouse model will allow the testing of
      potential therapeutic interventions.

PMID- 11230172
TI  - A bacterial artificial chromosome library for sequencing the complete human
      genome.
AB  - A 30-fold redundant human bacterial artificial chromosome (BAC) library with a
      large average insert size (178 kb) has been constructed to provide the
      intermediate substrate for the international genome sequencing effort. The DNA
      was obtained from a single anonymous volunteer, whose identity was protected
      through a double-blind donor selection protocol. DNA fragments were generated by
      partial digestion with EcoRI (library segments 1--4: 24-fold) and MboI (segment
      5: sixfold) and cloned into the pBACe3.6 and pTARBAC1 vectors, respectively. The
      quality of the library was assessed by extensive analysis of 169 clones for
      rearrangements and artifacts. Eighteen BACs (11%) revealed minor insert
      rearrangements, and none was chimeric. This BAC library, designated as "RPCI-11,"
      has been used widely as the central resource for insert-end sequencing, clone
      fingerprinting, high-throughput sequence analysis and as a source of mapped
      clones for diagnostic and functional studies.

PMID- 11230176
TI  - Nuclear background determines biochemical phenotype in the deafness-associated
      mitochondrial 12S rRNA mutation.
AB  - The pathogenetic mechanism of the human mitochondrial 12S rRNA gene mutation at
      position 1555, associated with non-syndromic deafness and aminoglycoside-induced
      deafness, has been investigated in 33 transformants obtained by transferring
      mitochondria from lymphoblastoid cell lines into human mitochondrial DNA (mtDNA)
      less (rho *206) cells. In this nearly constant nuclear background, 15
      transformants derived from five symptomatic individuals from a large Arab-Israeli
      family, carrying this mutation in homoplasmic form, exhibited significant
      decreases compared with nine control transformants in the rate of growth in a
      medium containing galactose instead of glucose, as well as in the rates of
      mitochondrial protein synthesis and of substrate-dependent respiration. Most
      significantly, these decreases were very similar to those observed in nine
      transformants derived from three asymptomatic members of the family. This result
      in transmitochondrial cybrids is in contrast to the differences in the same
      parameters previously demonstrated between the original lymphoblastoid cell lines
      derived from the symptomatic and asymptomatic members of the Arab-Israeli family.
      In addition, the intragroup variability in biochemical dysfunction among the
      lymphoblastoid cell lines from different symptomatic or asymptomatic or control
      individuals was significantly reduced in the derived mitochondrial transformants
      carrying the same nuclear background. These observations provide strong genetic
      and biochemical evidence in support of the idea that the nuclear background plays
      a determinant role in the phenotypic manifestation of the non-syndromic deafness
      associated with the A1555G mutation.

PMID- 11230177
TI  - Primary non-random X inactivation associated with disruption of Xist promoter
      regulation.
AB  - In this report we demonstrate primary non-random X chromosome inactivation
      following targeted mutagenesis of a region immediately upstream of XIST promoter
      P(1). In heterozygous animals there is a preferential inactivation of the
      targeted X chromosome in 80--90% of cells. The phenotype correlates with
      inappropriate activation of XIST in a proportion of the mutant XY embryonic stem
      cells. Strand-specific analysis revealed increased sense transcription initiating
      upstream of XIST promoter P(1). There was, however, no discernible effect on
      transcription from the antisense Tsix gene. We demonstrate that the in vitro and
      in vivo phenotypes are specifically attributable to the presence of a PGKneo
      cassette at the targeted locus. These findings are discussed in the context of
      understanding mechanisms of XIST gene regulation in X inactivation.

PMID- 11230178
TI  - Prediction of deleterious human alleles.
AB  - Single nucleotide polymorphisms (SNPs) constitute the bulk of human genetic
      variation, occurring with an average density of approximately 1/1000 nucleotides
      of a genotype. SNPs are either neutral allelic variants or are under selection of
      various strengths, and the impact of SNPs on fitness remains unknown.
      Identification of SNPs affecting human phenotype, especially leading to risks of
      complex disorders, is one of the key problems of medical genetics. SNPs in
      protein-coding regions that cause amino acid variants (non-synonymous cSNPs) are
      most likely to affect phenotypes. We have developed a straightforward and
      reliable method based on physical and comparative considerations that estimates
      the impact of an amino acid replacement on the three-dimensional structure and
      function of the protein. We estimate that approximately 20% of common human non
      synonymous SNPs damage the protein. The average minor allele frequency of such
      SNPs in our data set was two times lower than that of benign non-synonymous SNPs.
      The average human genotype carries approximately 10(3) damaging non-synonymous
      SNPs that together cause a substantial reduction in fitness.

PMID- 11230179
TI  - PTEN coordinates G(1) arrest by down-regulating cyclin D1 via its protein
      phosphatase activity and up-regulating p27 via its lipid phosphatase activity in
      a breast cancer model.
AB  - The tumour suppressor gene PTEN/MMAC1/TEP1 encodes a dual-specificity phosphatase
      that recognizes phosphatidylinositol-3,4,5-triphosphate and protein substrates.
      We have shown previously that over-expression of PTEN in a tetracycline
      controlled inducible system blocks cell cycle progression and induces apoptosis
      in MCF-7 breast cancer cells. Here, we demonstrate that over-expression of wild
      type PTEN leads to the suppression of cell growth through the blockade of cell
      cycle progression, an increase in the abundance of p27, a decrease in the protein
      levels of cyclin D1 and the inhibition of Akt phosphorylation. In contrast,
      expression of the phosphatase-dead mutant, C124S, promotes cell growth and has
      the opposite effect on the abundance of p27, cyclin D1 levels and the
      phosphorylation of Akt. The G129E mutant, which does not have lipid phosphatase
      activity but retains protein phosphatase activity, behaves like C124S except that
      the former causes decreases in cyclin D1 levels similar to wild-type PTEN.
      Therefore, PTEN exerts its growth suppression through lipid phosphatase-dependent
      and independent activities and most likely, via the coordinate effect of both
      protein phosphatase and lipid phosphatase activities. Addition of either estrogen
      or insulin abrogates PTEN-mediated up-regulation of p27 and partially blocks PTEN
      mediated growth suppression, whereas the combination of estrogen and insulin
      eliminates the alterations of p27 and cyclin D1 and completely blocks PTEN
      mediated growth suppression. Our findings demonstrate that PTEN blocks cell cycle
      progression differentially through down-regulating the positive cell cycle
      regulator, cyclin D1, by its protein phosphatase activity, and up-regulating the
      negative cell cycle regulator, p27, by its lipid phosphatase activity.

PMID- 11230180
TI  - PTEN inhibits insulin-stimulated MEK/MAPK activation and cell growth by blocking
      IRS-1 phosphorylation and IRS-1/Grb-2/Sos complex formation in a breast cancer
      model.
AB  - The tumour suppressor gene PTEN encodes a dual-specificity phosphatase that
      recognizes protein substrates and phosphatidylinositol-3,4,5-triphosphate. PTEN
      seems to play multiple roles in tumour suppression and the blockade of
      phosphoinositide-3-kinase signalling is important for its growth suppressive
      effects, although precise mechanisms are not fully understood. In this study, we
      show that PTEN plays a unique role in the insulin-signalling pathway in a breast
      cancer model. Ectopic expression of wild-type PTEN in MCF-7 epithelial breast
      cancer cells resulted in universal inhibition of Akt phosphorylation in response
      to stimulation by diverse growth factors and selective inhibition of
      MEK/extracellular signal-regulated kinase (ERK) phosphorylation stimulated by
      insulin or insulin-like growth factor 1 (IGF-1). The latter was accompanied by a
      decrease in the phosphorylation of insulin receptor substrate 1 (IRS-1) and the
      association of IRS-1 with Grb2/Sos, without affecting the phosphorylation status
      of the insulin receptor and Shc, nor Shc/Grb2 complex formation. The MEK
      inhibitor, PD980059, but not the PI3K inhibitor, wortmannin, abolished the effect
      of PTEN on insulin-stimulated cell growth. Without addition of insulin,
      wortmannin reduced PTEN-mediated growth suppression, whereas PD980059 had little
      effect, suggesting that PTEN suppresses insulin-stimulated cell growth by
      blocking the mitogen-activated protein kinase (MAPK) pathway. Furthermore,
      PD980059 treatment led to the downregulation of cyclin D1 and the suppression of
      cell cycle progression. Our data suggest that PTEN blocks MAPK phosphorylation in
      response to insulin stimulation by inhibiting the phosphorylation of IRS-1 and
      IRS-1/Grb2/Sos complex formation, which leads to downregulation of cyclin D1,
      inhibition of cell cycle progression and suppression of cell growth.

PMID- 11230181
TI  - WBSCR14, a gene mapping to the Williams--Beuren syndrome deleted region, is a new
      member of the Mlx transcription factor network.
AB  - Williams-Beuren syndrome (WBS) is a developmental disorder associated with
      haploinsufficiency of multiple genes at 7q11.23. Here, we report the functional
      characterization of WBS critical region gene 14 (WBSCR14), a gene contained in
      the WBS commonly deleted region. It encodes a basic-helix--loop--helix leucine
      zipper (bHLHZip) transcription factor of the Myc/Max/Mad superfamily. WBSCR14 is
      expressed in multiple tissues, including regions of the brain and the intestinal
      tract. WBSCR14 forms heterodimers with the bHLHZip protein Mlx to bind the DNA
      sequence CACGTG. Like Max, Mlx has no intrinsic transcriptional activity, but its
      association with Mad1, Mad4, Mnt or WBSCR14 can repress E-box-dependent
      transcription. Preliminary results suggest a possible role of WBSCR14 in growth
      control. Our data support the view that the Max-like bHLHZip protein, Mlx, is a
      key element of a transcription factor network. We thus suggest that WBSCR14 may
      contribute to some aspects of the WBS pathology.

PMID- 11230182
TI  - Mutation rates at two human Y-chromosomal microsatellite loci using small pool
      PCR techniques.
AB  - Polymorphic Y-chromosomal short tandem repeats (Y-STRs) are being employed for
      phylogenetic and evolutionary studies as well as for forensic applications.
      Precise knowledge of mutation types and rates is essential and has hitherto been
      obtained from computer simulation or small-sized father/son pairs, or derived
      from the more intensively studied autosomal STRs, respectively. To establish more
      accurate values we analysed about 18 000 DNA sequences isolated from sperm cells
      of three donors, representing highly validated offspring. Two loci were examined,
      i.e. DYS19 and DYS390. The methodology applied was small pool PCR with automated
      laser-induced fluorescence detection. The mutation rates for single repeat gains
      were determined as 0.18% [95% confidence interval (CI) 0.11--0.31%] for DYS390
      and 0.21% (95% CI 0.13--0.33%) for DYS19, and two-repeat changes occurred in the
      order of 0.01%. Assuming a similar rate for the loss of repeats, which could not
      be detected with our approach, we predict an overall mutation rate of
      approximately 0.4% per gamete per generation for both Y tetranucleotide loci.
      Moreover, these results support the stepwise mutation mechanism based on
      replication slippage. We expect this approach to be useful for individual
      mutation risk determination, as well as for studies concerning male history.

PMID- 11230183
TI  - Mutations in the regulatory domain of cystathionine beta synthase can
      functionally suppress patient-derived mutations in cis.
AB  - Human cystathionine beta--synthase (CBS) is an S-adenosylmethionine-regulated
      enzyme that plays a key role in the metabolism of homocysteine. Mutations in CBS
      are known to cause homocystinuria, an inborn error in metabolism. We previously
      developed a yeast functional assay for CBS and used it to characterize mutations
      found in homocystinuric patients. We discovered that many patient-derived
      mutations are functionally suppressed by deletion of the C-terminal 142 amino
      acids, which contain a 53 amino acid motif known as the CBS domain. This domain
      is found in a wide variety of proteins of diverse biological function. Here we
      have used a genetic screen to identify missense mutations in the C-terminal
      region of CBS that can suppress the most common patient mutation, I278T. Seven
      suppressor mutations were identified, four of which map to the CBS domain. When
      combined in cis with another pathogenic mutation, V168M, six of seven of the
      suppressor mutations rescued the yeast phenotype. Enzyme activity analyses
      indicate that the suppressors restore activity from <2% to 17--64% of the wild
      type levels. Analysis of the suppressor mutations in the absence of the
      pathogenic mutation shows that six of the seven suppressor alleles have lost
      enzymatic responsiveness to S-adenosylmethionine. Using homology modeling, we
      show that the suppressor mutations appear to map on one face of the CBS domain.
      Our results indicate that subtle changes to the C-terminus of CBS can restore
      activity to mutant proteins and provide a rationale for screening for compounds
      that can activate mutant CBS alleles.

PMID- 11230184
TI  - Association of acetylated histones with paternally expressed genes in the Prader-
      Willi deletion region.
AB  - Imprinted genes within the Prader-Willi/Angelman syndrome region of human
      chromosome 15q11-q13 are regulated by a mechanism involving allele-specific DNA
      methylation. Since transcriptional regulation by DNA methylation involves histone
      deacetylation, we explored whether differences in histone acetylation exist
      between the two parental alleles of SNRPN and other paternally expressed genes in
      the region by using a chromatin immunoprecipitation assay with antibodies against
      acetylated histones H3 and H4. SNRPN exon 1, which is methylated on the silent
      maternal allele, was associated with acetylated histones on the expressed
      paternal allele only. SNRPN intron 7, which is methylated on the paternal allele,
      was not associated with acetylated histones on either allele. The paternally
      expressed genes NDN, IPW, PWCR1 and MAGEL2 were not associated with acetylated
      histones on either allele. Treatment of the lymphoblastoid cells with
      trichostatin A, a histone deacetylase inhibitor, did not result in any changes to
      SNRPN expression or association of acetylated histones with exon 1. Treatment
      with 5-aza-deoxycytidine (5-aza-dC), which inhibits DNA methylation, resulted in
      activation of SNRPN expression from the maternal allele, but was not accompanied
      by acetylation of histones. Our finding of allele-specific association of
      acetylated histones with the SNRPN exon 1 region, which encompasses the
      imprinting center, suggests that histone acetylation at this site may be
      important for regulation of SNRPN and of other paternally expressed genes in the
      region. On the silent allele, 5-aza-dC treatment altered SNRPN expression, but
      not association with acetylated histones, suggesting that histone acetylation is
      a secondary event in the process of gene reactivation by CpG demethylation.

PMID- 11230246
TI  - Tonic excitatory input to the rostral ventrolateral medulla in Dahl salt
      sensitive rats.
AB  - The goal of the present study was to test the hypothesis that the balance of
      tonic excitation and inhibition of vasomotor neurons in the rostral ventrolateral
      medulla (RVLM) driven by excitatory amino acid (EAA)-mediated inputs to the RVLM
      is shifted toward excitation in Dahl salt-sensitive (DS) rats compared with Dahl
      salt-resistant (DR) rats. Glutamate and the EAA antagonist kynurenic acid were
      microinjected into the RVLM of chloralose-anesthetized DS and DR rats maintained
      on diets containing either 0.3% NaCl or 8.0% NaCl. DS rats had a higher arterial
      pressure than DR rats, and this difference was greatly exaggerated by high
      dietary salt intake. Bilateral injection of kynurenic acid (2.7 nmol) into the
      RVLM decreased mean arterial pressure by 16+/-2 mm Hg in DS rats fed a diet
      containing 0.3% NaCl, and this effect was significantly larger in DS rats fed the
      high-salt diet (40+/-2 mm Hg). In contrast, injections of kynurenic acid into the
      RVLM did not significantly decrease arterial pressure in DR rats fed either diet.
      In DR rats, the pressor response elicited by the injection of glutamate into the
      RVLM was potentiated in rats fed the high-salt diet. The glutamate-evoked pressor
      response was greater in DS rats compared with DR rats, and the response in DS
      rats was not influenced by the salt content of the diet. These data suggest that
      tonically active EAA inputs to the RVLM may contribute to salt-sensitive
      hypertension in the Dahl model.

PMID- 11230268
TI  - Mercury sphygmomanometers should not be abandoned: An advisory statement from the
      Council for High Blood Pressure Research, American Heart Association.

PMID- 11230269
TI  - Association between smoking and blood pressure: evidence from the health survey
      for England.
AB  - Cigarette smoking causes acute blood pressure (BP) elevation, although some
      studies have found similar or lower BPs in smokers compared with nonsmokers.
      Cross-sectional data from 3 years (1994 to 1996) of the annual Health Survey for
      England were used to investigate any difference in BP between smokers and
      nonsmokers in a nationally representative sample of adults (>/=16 years old).
      Randomly selected adults (33 860; 47% men) with valid body mass index (BMI) and
      BP measurements provided data on smoking status (never, past, or current) and
      were stratified into younger (16 to 44 years old) and older (>/=45 years old) age
      groups. Analyses provided between 89% and 94% power to detect a difference of 2
      mm Hg systolic BP between smokers and nonsmokers in the 4 age/gender strata
      (alpha=0.05). Older male smokers had higher systolic BP adjusted for age, BMI,
      social class, and alcohol intake than did nonsmoking men. No such differences
      were seen among younger men or for diastolic blood pressure in either age group.
      Among women, light smokers (1 to 9 cigarettes/d) tended to have lower BPs than
      heavier smokers and never smokers, significantly so for diastolic BP. Among men,
      a significant interaction between BMI and the BP-smoking association was
      observed. In women, BP differences between nonsmokers and light smokers were most
      marked in those who did not drink alcohol. These data show that any independent
      chronic effect of smoking on BP is small. Differences between men and women in
      this association are likely to be due to complex interrelations among smoking,
      alcohol intake, and BMI.

PMID- 11230270
TI  - Effects of smoking cessation on changes in blood pressure and incidence of
      hypertension: a 4-year follow-up study.
AB  - We performed the present study to investigate the effects of smoking cessation on
      changes in blood pressure and incidence of hypertension. We evaluated 8170
      healthy male employees at a steel manufacturing company who had received
      occupational health examinations at the company's health care center in 1994 and
      were reexamined in 1998. Adjustment covariates were the baseline age, body mass
      index, cigarette smoking, alcohol consumption, exercise, family history of
      hypertension, systolic or diastolic blood pressure, and changes in body mass
      index and alcohol consumption during the follow-up period. The adjusted relative
      risks of hypertension in those who had quit smoking for <1, 1 to 3, and >/=3
      years were 0.6 (95% CI 0.2 to 1.9), 1.5 (95% CI 0.8 to 2.8), and 3.5 (95% CI 1.7
      to 7.4), respectively, compared with current smokers. The trends for increased
      risk of hypertension for longer periods of smoking cessation were observed in
      subgroups of those who maintained weight as well as those who gained weight after
      smoking cessation. The adjusted increments in both systolic and diastolic blood
      pressure were higher in those who had quit for >/=1 year than in current smokers.
      These trends among weight losers, as well as gainers and maintainers, were
      similar. We observed progressive increases in blood pressure with the
      prolongation of cessation in men, although at this time the mechanism remains
      unknown and must be clarified. This study implies that the cessation of smoking
      may result in increases in blood pressure, hypertension, or both.

PMID- 11230271
TI  - T wave alternans and ventricular arrhythmias in arterial hypertension.
AB  - Patients with a positive microvolt-level T wave alternans (TWA) are characterized
      by an increased risk of ventricular tachyarrhythmias. Arterial hypertension leads
      to an increase of sudden cardiac death risk, particularly if left ventricular
      hypertrophy is present. The aim of this study was to investigate the value of TWA
      in patients with arterial hypertension. Fifty-one consecutive patients were
      included in the study. TWA analysis was performed with patients sitting on a
      bicycle ergometer and exercising with a gradual increase of workload to maintain
      a heart rate of at least 105/min. After recording 254 consecutive low-noise-level
      heartbeats, the exercise test was stopped. The ECG signals were digitally
      processed by a spectral analysis method. The magnitude of TWA was measured at a
      frequency of 0.5 cycle per beat. A TWA was defined as positive if the ratio
      between TWA and noise level was >3.0 and the amplitude of the TWA was >1.8
      microV. Eight of the 51 patients (16%) showed a positive TWA. If left ventricular
      hypertrophy was present, the prevalence of TWA was higher (33.3% versus 8.3%;
      P:<0.05). Sensitivity concerning a previous arrhythmic event was 73%, and
      specificity was 100%. The alternans ratio was significantly higher in patients
      with a previous event (39.3+/-62.3 versus 2.4+/-4.6; P:<0.001), as was the
      cumulative alternans voltage (4.7+/-4.1 versus 1.6+/-1.9 microV; P:<0.001). In 16
      patients invasively investigated by an electrophysiological study, a significant
      correlation between inducibility of tachyarrhythmias and a positive TWA result
      was found (Spearman R:=0.36, P:=0.01). We conclude that the arrhythmic risk of
      patients with arterial hypertension is markedly increased if microvolt-level TWA
      is present. The prevalence of TWA is higher in patients with left ventricular
      hypertrophy.

PMID- 11230273
TI  - Mortality after coronary artery occlusion in different models of cardiac
      hypertrophy in rats.
AB  - Chronic treatment with minoxidil induces cardiac trophic and sympathetic
      responses, which may increase the propensity for lethal arrhythmias. To test this
      hypothesis, acute coronary artery occlusion was performed in conscious
      normotensive rats treated for 2 or 5 weeks with minoxidil with the use of a 2
      stage approach to cause a myocardial infarction. For comparison, rats with
      aortocaval (A-V) shunts and spontaneously hypertensive rats (SHR) were studied.
      Minoxidil increased left ventricular and right ventricular weights by 15% to 20%,
      and the A-V shunt increased these weights by 30% to 40%. In SHR, left ventricular
      weight was increased by 50%, and right ventricular weight was increased by 25%.
      In rats treated with minoxidil for 5 weeks, coronary artery occlusion caused a
      rapid and marked mortality, and 4 hours after myocardial infarction, only 18% of
      these rats were alive versus 61% of the control rats. In rats with the A-V shunt,
      coronary artery occlusion was also associated with increased mortality, and after
      6 hours, 33% were still alive compared with 59% of the control rats. In contrast,
      SHR with marked hypertension and cardiac hypertrophy showed only a minor increase
      in mortality (survival rates were 53% versus 60% in SHR versus Wistar-Kyoto rats,
      respectively). Mortality was preceded by high arrhythmia scores, and ventricular
      fibrillation was the cause of death. Discontinuation of minoxidil for 1 week,
      sympathetic blockade with nadolol or clonidine, or blockade of the renin
      angiotensin system with enalapril or losartan did not improve minoxidil-induced
      excess mortality. We conclude that ventricular stretch and other mechanisms (eg,
      cardiac vagal activity) in rats appear to be more potent than hypertension
      induced left ventricular hypertrophy in predisposing for lethal arrhythmias in
      the setting of acute ischemia.

PMID- 11230272
TI  - Exercise intolerance in rats with hypertensive heart disease is associated with
      impaired diastolic relaxation.
AB  - A decrease in functional capacity is one of the most important clinical
      manifestations of hypertensive heart disease, but its cause is poorly understood.
      Our purpose was to evaluate potential causes of hypertension-induced exercise
      intolerance, focusing on identifying the type(s) of cardiac dysfunction
      associated with the first signs of exercise intolerance during the course of
      hypertensive heart disease. Exercise capacity was measured weekly in Dahl salt
      sensitive rats as they developed hypertension as well as in Dahl salt-resistant
      control rats. Exercise capacity was unchanged from baseline during the first 8
      weeks of hypertension, suggesting that hypertension itself did not cause exercise
      intolerance. After 9 to 12 weeks of hypertension, exercise capacity decreased in
      salt-sensitive rats but not in control rats. After 10 weeks of hypertension,
      indices of diastolic function (early truncation of the E wave), as assessed by
      echocardiography at rest, were decreased in the salt-sensitive rats. When
      exercise capacity had decreased by approximately 25% in a rat, the heart was
      isolated, and left ventricular (LV) compliance and systolic function were
      measured. At that time point, LV hypertrophy was modest (an approximately 20%
      increase in LV mass), and systolic function was normal or supernormal, indicating
      that exercise intolerance began during "compensated" LV hypertrophy. Passive LV
      compliance remained normal in salt-sensitive rats. Thus, in this model of
      hypertensive heart disease, exercise intolerance develops during the compensated
      stage of LV hypertrophy and appears to be due to changes in diastolic rather than
      systolic function. However, studies in which LV function is assessed during
      exercise are needed to conclusively define the roles of systolic and diastolic
      dysfunction in causing exercise intolerance.

PMID- 11230275
TI  - Effect of lead on nitric oxide synthase expression in coronary endothelial cells:
      role of superoxide.
AB  - Chronic exposure to low levels of lead causes hypertension (HTN) in humans and
      animals. We have previously shown that increased reactive oxygen species (ROS)
      leads to enhanced NO inactivation, depressed NO bioavailability, and compensatory
      upregulation of NO synthases (NOSs) in rats with lead-induced HTN. We have
      further demonstrated increased ROS generation with lead exposure in cultured
      endothelial cells. In the present study, we tested the effect of lead (medium
      containing lead acetate, 1 ppm) alone and with either the superoxide dismutase
      mimetic agent tempol or a potent antioxidant lazaroid compound (both at 10(-8)
      and 10(-7) mol/L) on endothelial NOS expression and NO production in cultured
      human coronary endothelial cells. Lead-treated cells showed a significant
      upregulation of endothelial NOS (eNOS) protein abundance (P:<0.002) and a
      significant increase in the production of NO metabolites (NO(2)(-) +NO(3)(-)=NOx,
      P:<0.01). Cotreatment with either tempol or lazaroid abrogated the lead-induced
      upregulation of eNOS protein and NO(x) production. In contrast, tempol and
      lazaroid had no effect on either eNOS protein expression or NO(x) production in
      the control cells. Thus, lead exposure upregulated eNOS expression in vitro,
      simulating the results of our previous in vivo studies. This phenomenon points to
      a direct as opposed to an indirect (eg, HTN-mediated) effect of lead on NO
      metabolism. The reversal of lead effect by lazaroid and the cell-permeable
      superoxide dismutase-mimetic agent tempol suggests that lead exposure increases
      generation and/or reduces dismutation of superoxide, which in turn promotes
      oxidative stress, enhances NO inactivation, and elicits a compensatory
      upregulation of eNOS whose expression is negatively regulated by NO.

PMID- 11230274
TI  - Alterations of intrarenal adrenomedullin and its receptor system in heart failure
      rats.
AB  - Calcitonin receptor-like receptor/receptor activity-modifying protein 2
      (CRLR/RAMP2) and CRLR/RAMP3 complexes have been reported to be specific
      adrenomedullin (AM) receptors. In the present study, we evaluated the
      pathophysiological significance of renal AM and its receptor system in aortocaval
      shunt (ACS) rats. Renal AM levels were measured serially during 5 weeks after the
      operation. Renal gene expressions of AM, CRLR, RAMP2, and RAMP3 were measured at
      2 weeks (decompensated phase) and 5 weeks (compensated phase) after the
      operation. Immunohistochemical localizations of renal AM were also evaluated.
      Furthermore, the relations between urinary sodium excretion (UNaV) and renal AM
      levels were evaluated. Renal AM levels were higher in ACS than in control animals
      only at 1, 2, and 3 weeks after the operation. At 2 weeks after the operation,
      renal AM mRNA expression was also higher in ACS than in control animals. CRLR,
      RAMP2, and RAMP3 mRNAs were expressed in the kidney, but there were no
      differences between the 2 groups. Immunohistochemistry revealed the positive AM
      immunostaining within the renal tubular cells, and it was more intense in ACS
      than in control animals. There were significant correlations between UNaV and
      renal AM levels. At 5 weeks after the operation, there were no differences in
      mRNA levels of AM, CRLR, RAMP2, and RAMP3 between the 2 groups. There was a
      significant correlation between UNaV and medullary AM levels. The present
      findings suggest that increased renal AM levels in decompensated heart failure,
      presumably due to increased AM production in renal tubules, in part, are involved
      in the regulation of sodium excretion.

PMID- 11230276
TI  - Effect of adrenomedullin on placental arteries in normal and preeclamptic
      pregnancies.
AB  - Adrenomedullin is a potent vasodilatory peptide with plasma levels that increase
      during pregnancy. Although fetoplacental adrenomedullin levels are reported to
      increase in preeclampsia, maternal plasma levels may be elevated or decreased, or
      they may resemble those in normal pregnancy. In other hypertensive conditions,
      adrenomedullin increases. Therefore, we hypothesized that maternal plasma
      adrenomedullin levels would be higher in hypertensive pregnancies than in
      normotensive pregnancies and that the higher placental resistance found in
      preeclamptic pregnancies results from blunted activity of adrenomedullin on the
      vasculature. Adrenomedullin concentrations in plasma from women with normotensive
      pregnancies, gestational hypertension, and preeclampsia were determined by
      radioimmunoassay. Stem villous arteries from normotensive and preeclamptic
      pregnancies were dissected and mounted on a wire myograph system. Arteries were
      first preconstricted to 80% of their maximum constriction with U46619, a
      thromboxane A(2) mimetic, and exposed to cumulative doses of adrenomedullin
      (1x10(-)(9) to 3x10(-)(7) mol/L). Contrary to our hypothesis, there were no
      significant differences in maternal plasma adrenomedullin levels among patients
      with normal pregnancies, gestational hypertension, and preeclampsia.
      Adrenomedullin significantly relaxed arteries from both normal and preeclamptic
      placentas, but there was no significant difference between the 2 groups. During
      normal pregnancy, adrenomedullin may contribute to the low placental vascular
      resistance. This pathway appears to be intact in preeclampsia. We conclude that
      the increased placental vascular resistance observed in preeclampsia is due
      neither to reduced adrenomedullin secretion nor to an attenuated vascular
      responsiveness. Moreover, unlike other hypertensive disorders, there is no
      compensatory rise in circulating adrenomedullin levels.

PMID- 11230277
TI  - Brief review: hypertension in pregnancy : a manifestation of the insulin
      resistance syndrome?
AB  - Pregnancy-induced hypertension (PIH), which includes both gestational
      hypertension and preeclampsia, is a common and morbid pregnancy complication for
      which the pathogenesis remains unclear. Emerging evidence suggests that insulin
      resistance, which has been linked to essential hypertension, may play a role in
      PIH. Conditions associated with increased insulin resistance, including
      gestational diabetes, polycystic ovary syndrome, and obesity, may predispose to
      hypertensive pregnancy. Furthermore, metabolic abnormalities linked to the
      insulin resistance syndrome are also observed in women with PIH to a greater
      degree than in normotensive pregnant women: These include glucose intolerance,
      hyperinsulinemia, hyperlipidemia, and high levels of plasminogen activator
      inhibitor-1, leptin, and tumor necrosis factor-alpha. These observations suggest
      the possibility that insulin resistance may be involved in the pathogenesis of
      PIH and that approaches that improve insulin sensitivity might have benefit in
      the prevention or treatment of this syndrome, although this requires further
      study.

PMID- 11230278
TI  - Nifedipine increases endothelial nitric oxide bioavailability by antioxidative
      mechanisms.
AB  - Short-term treatment of the endothelium with dihydropyridine calcium antagonists
      resulted in an increased release in NO that is not due to a modulation of L-type
      calcium channels, because macrovascular endothelial cells do not express this
      channel. We investigated whether long-term (48 hours) treatment of porcine
      endothelial cell cultures with the dihydropyridine calcium antagonist nifedipine
      resulted in a similar enhanced NO liberation. Regarding to the underlying
      mechanism, we examined whether (1) nifedipine changed the mRNA and protein levels
      of the constitutive endothelial NO synthase (NOS) in endothelial cell cultures or
      (2) nifedipine exerts an NO protective effect via its antioxidative properties,
      as revealed in a cell culture model and with native endothelium from porcine
      coronary arteries. Nifedipine induced a significant time- and concentration
      dependent increase (132+/-47%, 1 micromol/L, 40 minutes' incubation) in the basal
      NO liberation (oxyhemoglobin assay). This increased NO release was not due to
      elevated NOS (type III) mRNA (Northern blot analysis) and protein (Western blot
      analysis) levels. However, nifedipine (both short- and long-term treatment)
      significantly reduced the basal and glucose (20 and 30 mmol/L)-stimulated
      formation of reactive oxygen species (lucigenin assay) of endothelial cell
      cultures and native cells. We conclude that the calcium antagonist nifedipine
      enhances the bioavailability of endothelial NO without significantly altering the
      NOS (type III) mRNA and protein expression, possibly via an antioxidative
      protection. This increased NO availability may cause part of the vasodilation and
      might contribute to the antithrombotic, antiproliferative, and
      antiatherosclerotic effects of dihydropyridine calcium antagonists.

PMID- 11230279
TI  - Nitric oxide and central antihypertensive drugs: one more difference between
      catecholamines and imidazolines.
AB  - NO is known to be involved in the peripheral and central regulation of the
      cardiovascular function. It plays a neuromodulatory role via a direct action on
      presynaptic nerve terminals, stimulating the release of gamma-aminobutyric acid,
      glutamate, and norepinephrine. Our aim was to study the possible role of NO in
      the cardiovascular effects of the central antihypertensive drugs clonidine,
      rilmenidine, and alpha-methyl-norepinephrine (alpha-MNA). Sites and mechanisms of
      the hypotensive action of these drugs were different; clonidine and rilmenidine
      acted on imidazoline receptors in the nucleus reticularis lateralis, whereas
      alpha-MNA acted upon alpha(2)-adrenoceptors in the nucleus tractus solitarius.
      The influence of N:(G)-nitro-L-arginine, an NO synthase inhibitor, on the central
      hypotensive effects of these drugs was investigated in pentobarbital-anesthetized
      rabbits. The intracisternal (IC) administration of alpha-MNA (30 microg/kg)
      induced hypotension (79+/-2 versus 103+/-4 mm Hg) and bradycardia (222+/-8 versus
      278+/-4 bpm) (P:<0.05) (n=5). Clonidine (0.07 microg/kg IC) also induced
      hypotension (69+/-5 versus 99+/-4 mm Hg) and bradycardia (266+/-7 versus 306+/-10
      bpm) (P:<0.05) (n=5). In addition to clonidine, rilmenidine (1 microg/kg IC)
      induced hypotension (64+/-4 versus 97+/-4 mm Hg) and bradycardia (264+/-11 versus
      310+/-4 bpm) (P:<0.05) (n=5). Pretreatment with N:(G)-nitro-L-arginine (900
      microg/kg IC) completely prevented the hypotensive effect of alpha-MNA but
      influenced the cardiovascular effects of neither clonidine nor rilmenidine. These
      results confirm that imidazoline drugs, such as clonidine, rilmenidine, and the
      catecholamine alpha(2)-adrenoceptor agonist alpha-MNA, have distinct mechanisms
      of action.

PMID- 11230280
TI  - Hypothesis: Beta-adrenergic receptor blockers and weight gain: A systematic
      analysis.
AB  - One of the arguments put forward against the primary use of beta-blockers has
      been concern about adverse metabolic effects, such as unfavorable effects on
      lipids or insulin sensitivity. Another less-appreciated potential drawback is
      their propensity to cause weight gain in some patients. In 8 evaluable
      prospective randomized controlled trials that lasted >/=6 months, body weight was
      higher in the beta-blocker than in the control group at the end of the study. The
      median difference in body weight was 1.2 kg (range -0.4 to 3.5 kg). A regression
      analysis suggested that beta-blockers were associated with an initial weight gain
      during the first few months. Thereafter, no further weight gain compared with
      controls was apparent. There was no relationship between demographic
      characteristics and changes in body weight. Based on these observations, the
      first-line use of beta-blockers in obese hypertensive patients should be
      reviewed. Obesity management in overweight hypertensive patients may be more
      difficult in the face of beta-blocker treatment.

PMID- 11230281
TI  - Structural vascular changes in hypertension: role of angiotensin II, dietary
      sodium supplementation, and sympathetic stimulation, alone and in combination in
      rats.
AB  - Elevated circulating angiotensin (Ang) II levels, dietary sodium, and sympathetic
      stimulation are recurrent themes of hypertension research, but their in vivo
      interaction in physiologically meaningful doses has not been adequately
      investigated. In this study, the interaction of a subpressor dose of Ang II (50
      ng. kg(-1). min(-1) SC), 2% NaCl diet, and sympathetic stimulation in the form of
      overnight cold exposure was investigated in the development of hypertension and
      of structural vascular changes in male Sprague-Dawley rats. There were 8
      experimental groups: sham operation and treatment (control), Ang II, 2% NaCl
      diet, cold exposure (5 degrees C), Ang II plus 2% NaCl diet, Ang II plus cold
      exposure, cold exposure plus 2% NaCl diet, and Ang II plus 2% NaCl diet plus cold
      exposure (triple treatment). For each group, the duration of treatment was 12
      weeks. Morphometric measurements of maximally dilated, in situ fixed, second
      order (250 to 320 microm OD), intermediate-size (100 to 150 microm OD), and small
      (50 to 100 microm OD) mesenteric arteries were performed, and wall-to-lumen
      ratios (W/L) were calculated. During the 12-week study, the blood pressure (BP)
      load (the area under the systolic BP curve) of rats receiving the combined
      treatment of Ang II and 2% NaCl diet was increased (P:<0.05), and that of rats
      receiving the combined treatment of cold exposure and 2% NaCl diet was decreased
      (P:<0.05); there were no BP changes in the remaining groups of rats. The most
      pronounced changes among groups occurred in W/L of small resistance arteries. The
      W/L of small arteries increased in Ang II-treated (P:<0.01) and in cold-stressed
      rats (P:<0.01). The effect of Ang II was potentiated by the addition of a 2% NaCl
      diet. In contrast, the addition of 2% NaCl diet to cold stress reduced the W/L of
      small arteries (P:<0.01). No other positive or negative synergism occurred among
      groups, including the rats receiving triple treatment. The findings confirm the
      potentiation of the hypertensinogenic and vascular trophic effects of Ang II by a
      high-sodium diet but do not provide evidence for synergism between Ang II and
      sympathetic stimulation. The finding of hypotension and reduced W/L of small
      resistance arteries in rats receiving the combined treatment of cold stress and
      high-sodium diet is unique because there are few known nonpharmacological
      vascular "hypotrophic" stimuli. The ultimate test of the hypertensinogenic
      potential of pressor stimuli alone or in combination is their long-term
      administration in physiologically meaningful doses to experimental animals.

PMID- 11230282
TI  - Ascorbic acid status and subsequent diastolic and systolic blood pressure.
AB  - Free radicals and oxidation are involved in several aspects of blood pressure
      physiology. We investigated the relationship between blood pressure and
      antioxidants, including plasma ascorbic acid (AscA), in a 17-week controlled-diet
      study. Study subjects included 68 men aged 30 to 59 years who had a mean
      diastolic blood pressure of 73.4 mm Hg and a mean systolic blood pressure of
      122.2 mm Hg. One month of vitamin C depletion was followed by 1-month repletion
      with 117 mg/d, repeated twice. All food and drink were provided in the study.
      Subjects did not smoke or drink alcohol, all consumed fruits and vegetables, and
      body weight was maintained. Plasma was assayed periodically for AscA, alpha
      tocopherol, carotenoids, and lipids. Plasma AscA was inversely related to
      diastolic blood pressure 1 month later (correlation -0.48, P:<0.0001). Persons in
      the bottom fourth of the plasma AscA distribution had >7 mm Hg higher diastolic
      blood pressure than did those in the top fourth of the plasma AscA distribution.
      Multivariate analysis with control for age, body mass index, other plasma
      antioxidants, and dietary energy, calcium, fiber, sodium, and potassium did not
      reduce the plasma AscA effect. One fourth of the variance in diastolic blood
      pressure was accounted for by plasma AscA alone. Plasma AscA was also
      significantly associated with systolic blood pressure in logistic regression.
      Vitamin C may be an important component of the effectiveness of fruits and
      vegetables in the reduction in blood pressure, and tissue AscA levels may be
      important in the maintenance of low blood pressure. Long-term intervention
      studies are warranted.

PMID- 11230283
TI  - Bbs and bullets: the impact of dietary factors on blood pressure.

PMID- 11230284
TI  - Inhibition of neointima by angiotensin-converting enzyme inhibitor in porcine
      coronary artery balloon-injury model.
AB  - Because hepatocyte growth factor (HGF) stimulates growth of endothelial cells
      exclusively without replication of vascular smooth muscle cells, we hypothesized
      that HGF may play a role in cardiovascular disease. In human vascular smooth
      muscle cells, angiotensin II suppressed local vascular HGF production in a dose
      dependent manner. Using a rat balloon-injury carotid artery model, we
      demonstrated that blockade of angiotensin II inhibited neointimal formation,
      accompanied by a significant increase in local HGF production. However, the
      relation of vascular HGF to endothelial function was not clarified. Moreover, it
      is important to test the hypothesis in animal models that are more similar to
      human restenosis. Thus, in the present study, we used a porcine coronary artery
      balloon-injury model to study the role of angiotensin II in regulation of the
      local HGF system in vivo. Expression of HGF mRNA was significantly decreased in
      balloon-injured coronary arteries versus intact vessels. An angiotensin
      converting enzyme (ACE) inhibitor (perindopril) significantly inhibited
      neointimal formation after balloon injury compared with vehicle (P:<0.05). In
      addition, vasodilator response of balloon-injured coronary arteries to bradykinin
      was restored by perindopril treatment, whereas no vasodilator response was
      observed in balloon-injured vessels treated with vehicle. Vasodilator response of
      balloon-injured arteries induced by perindopril was completely abolished by N:(w)
      nitro-L-arginine methyl ester. Of particular interest, vascular HGF mRNA was
      significantly increased in balloon-injured vessels treated with perindopril as
      compared with vehicle. Overall, the present study demonstrated that ACE inhibitor
      significantly inhibited neointimal formation, accompanied by significant
      improvement of endothelial dysfunction and a significant increase in local
      vascular HGF mRNA in vivo in a porcine coronary artery balloon-injury model.
      Given the strong mitogenic activity of HGF on endothelial cells, improvement of
      endothelial dysfunction by perindopril might be due to increased local HGF
      expression through enhancement of reendothelialization after balloon injury, in
      addition to its direct effect, ACE inhibition. Downregulation of the local
      vascular HGF system may play an important role in the pathogenesis of
      cardiovascular disease.

PMID- 11230285
TI  - Renal endothelin ET(A)/ET(B) receptor imbalance differentiates salt-sensitive
      from salt-resistant spontaneous hypertension.
AB  - It is unclear why a subgroup of patients with essential hypertension develop salt
      sensitive hypertension with progression of target organ damage over time. We
      evaluated the role of the renal endothelin (ET) system in the stroke-prone
      spontaneously hypertensive rat (SHRSP) model of salt-sensitive spontaneous
      hypertension (SS-SH) compared with the spontaneously hypertensive rat (SHR) model
      of salt-resistant spontaneous hypertension (SR-SH). Both strains were studied
      after either sham-operation on a normal diet (Sham) or after unilateral
      nephrectomy and high NaCl loading (NX-NaCl) with 4% NaCl in diet for 6 weeks
      (n=10, respectively). Systolic blood pressure (SBP) increased only in SHRSP-NX
      NaCl compared with SHRSP-Sham (250+/-6 versus 172+/-5 mm Hg, P:<0.0001). SBP
      remained unchanged in SHR-NX-NaCl compared with SHR-Sham. In SHRSP-NX-NaCl
      animals, urinary albumin and ET-1 excretion, renal ET-1 mRNA expression,
      glomerulosclerosis index, and tubulointerstitial damage index were elevated
      compared with SHRSP-Sham (P:<0.05, respectively), whereas no significant changes
      were found in SHR after NX-NaCl. Urinary sodium excretion (U(Na(+))) was
      significantly reduced by 38% in SHRSP-NX-NaCl compared with SHR-NX-NaCl
      (P:<0.005, respectively). SHR animals showed a similar increase in both renal
      ET(A) and ET(B) receptor densities after NX-NaCl (2.2-fold, P:<0.05). In
      contrast, SHRSP-NX-NaCl developed a significantly more pronounced increase in
      ET(A) compared with ET(B) binding (4.7-fold versus 2.4-fold, P:<0.05, compared
      with SHRSP-Sham, respectively), resulting in a significant 2.1-fold increase in
      ET(A)/ET(B) receptor ratio only in the SHRSP-NX-NaCl (P:<0.05). Thus, activation
      of the renal ET system together with an increased ET(A)/ET(B) receptor ratio may
      contribute to the development and progression of SS-SH.

PMID- 11230287
TI  - Association analysis of beta(2)-adrenergic receptor polymorphisms with
      hypertension in Japanese.
AB  - Significant evidence has been provided for the pathophysiological involvement of
      the beta(2)-adrenergic receptor (ADRB2) in hypertension. Among ADRB2
      polymorphisms identified to date, 2 amino acid substitutions, Arg16Gly and
      Gln27Glu, and a promoter variant, T-47C, are considered functionally important.
      In particular, Arg16Gly was shown to be associated with hypertension in black and
      white subjects. To investigate the relevance of ADRB2 polymorphisms to
      hypertension, we undertook an extensive association study in a Japanese
      population. An association was tested in 2 ways. First, a case-control study was
      conducted in 842 hypertensive and 633 normotensive subjects. In addition to the
      overall comparison between case and control groups, each was stratified by body
      mass index and compared with an independent panel of 525 diabetic subjects.
      Second, ANOVA and multivariate analyses were performed to test the significance
      of an association between ADRB2 genotype and the level of blood pressure within
      the entire population except for 395 subjects who had been under treatment for
      hypertension. Although no significant association was observed for Arg16Gly and T
      47C, 2 analytical methods indicated a marginal association (P:=0.01 to 0.04)
      between the Glu27 variant and lower blood pressure levels. Given such a
      normotensive propensity, the odds ratio for Glu27 versus Gln27 allele frequencies
      was estimated to be 0.74, with a wide confidence interval (95% CI, 0.55 to 0.99)
      reflecting the low Glu27-allele frequency (6% to 8%) in Japanese. There were no
      apparent confounding influences of obesity and diabetes on the postulated
      association. Our data suggest that 3 ADRB2 polymorphisms tested are unlikely to
      confer principal genetic susceptibility for hypertension in the Japanese
      population. However, further investigation is warranted to clarify the relevance
      of ADRB2 polymorphisms to blood pressure regulation.

PMID- 11230286
TI  - T+31C polymorphism of angiotensinogen gene and essential hypertension.
AB  - A common variant at codon 235 of the angiotensinogen gene with methionine to
      threonine amino acid substitution (AGT M235T) has been reported as a genetic risk
      for essential hypertension. However, the frequency of AGT T235 was heterogeneous
      among races, and a positive association between AGT M235T and hypertension was
      not settled. To examine the association in a general population of Japanese
      (n=4013), we introduced the TaqMan polymerase chain reaction method and examined
      the relation between hypertension and T+31C polymorphism, which was in absolute
      linkage disequilibrium with AGT M235T. The C+31 allele of AGT was significantly
      associated with the positive family history of hypertension (FH) but not with the
      presence of hypertension or blood pressure. The subjects with CC tended to have
      hypertensive relatives, especially a hypertensive father or siblings, and its
      statistical significance was stronger in men. Adjustment of confounding factor
      did not alter the results of simple association study, suggesting that this
      positive association with FH is independent and significant. Our findings
      revealed that the TaqMan polymerase chain reaction method is a powerful tool for
      genetic association study with a large number of subjects and that AGT T+31C is
      significantly associated with paternal FH.

PMID- 11230288
TI  - Exclusion of the ACE D/I gene polymorphism as a determinant of endothelial
      dysfunction.
AB  - A deletion/insertion (D/I) polymorphism within the ACE gene may increase the risk
      of cardiovascular events through still unknown mechanisms. The latter may involve
      increased angiotensin II-induced NO breakdown and/or reduced agonist-mediated NO
      release. We therefore investigated whether the D allele of the ACE gene affects
      endothelium-dependent vasodilatation in mild-to-moderate primary hypertensive
      patients and healthy normotensive subjects. We compared in a cross-sectional
      study the forearm blood flow response of the 3 D/I genotypes with 5 incrementally
      increasing doses of the endothelium-dependent vasodilator acetylcholine (0.15,
      0.45, 1.5, 4.5, and 15 microg. 100 mL(-1). min(-1)) in 142 subjects: 103 mild-to
      moderate uncomplicated primary hypertensives (49.3+/-9.1 years old, 152+/-11/99+/
      5 mm Hg) and 39 normotensives (44.6+/-15.3 years old, 122+/-12/78+/-6 mm Hg). We
      also assessed the endothelium-independent vasodilatation in the forearm, as blood
      flow response to 3 incrementally increasing doses of sodium nitroprusside (1, 2,
      and 4 microg. 100 mL(-1). min(-1)). The overall genotype distribution was II,
      n=10; ID, n=70; and DD, n=62. It did not differ significantly between primary
      hypertensives and normotensives. A significant blunting of endothelium-dependent
      vasodilatation in primary hypertensive patients compared with normotensive
      subjects (P:<0.001) was found. No effect of the DI genotype on endothelium
      dependent and -independent vasodilatation was detected. Thus, these results
      obtained in a relatively large population do not support the contention that the
      D allele is associated with a blunting of either stimulated endothelial NO or
      donated NO responses in both mild-to-moderate primary hypertensive patients and
      normotensive subjects.

PMID- 11230290
TI  - Signaling events mediating the additive effects of oleic acid and angiotensin II
      on vascular smooth muscle cell migration.
AB  - Obese hypertensive patients with cardiovascular risk factor clustering and
      increased risk for atherosclerotic disease have increased plasma nonesterified
      fatty acid levels, including oleic acid (OA), and a more active renin-angiotensin
      aldosterone system. Vascular smooth muscle cell (VSMC) migration and
      proliferation participate in the development of atherosclerotic plaque. OA and
      angiotensin (Ang) II induce synergistic mitogenic responses in VSMCs through
      sequential signaling pathways dependent on the activation of protein kinase C
      (PKC), oxidants (reactive oxygen species, ROS), and extracellular signal
      regulated kinase (ERK) activation. We tested the hypotheses that (1) OA and Ang
      II have additive or synergistic effects on VSMC migration and (2) PKC, ROS, and
      mitogen-activated protein kinase are critical signaling molecules. OA at 100
      micromol/L increases VSMC migration 60+/-10% over control (P:<0.001). Ang II (10(
      )(9) mol/L) increases VSMC migration by 62+/-13% and 73% over control,
      respectively (P:<0.01). Coincubation of cells with OA and Ang II produces a
      nearly additive increase in VSMC cell migration at 107+/-20% (P:<0.01). Increases
      in VSMC migration induced by OA alone and combined with Ang II were reduced by
      PKC inhibition and downregulation. VSMC migration in response to OA alone and
      with Ang II was also inhibited by N:-acetyl-cysteine, MEK inhibition, and ERK
      antisense. VSMC migration in response to OA alone or combined with Ang II is
      dependent on activation of PKC, ROS, and ERK activation, further raising the
      possibility that increased plasma nonesterified fatty acids and an activated
      renin-angiotensin-aldosterone system in subjects with the risk factor cluster
      contribute to accelerated atherosclerosis through a PKC, ROS, and ERK-dependent
      signaling pathway.

PMID- 11230289
TI  - Angiotensin II relaxes microvessels via the AT(2) receptor and Ca(2+)-activated
      K(+) (BK(Ca)) channels.
AB  - Angiotensin II (Ang II) is one of the most potent vasoconstrictor substances, yet
      paradoxically, Ang II may dilate certain vascular beds via an undefined
      mechanism. Ang II-induced vasoconstriction is mediated by the AT(1) receptor,
      whereas the relative expression and functional importance of the AT(2) receptor
      in regulating vascular resistance and blood pressure are unknown. We now report
      that Ang II induces relaxation of mesenteric microvessels and that this
      vasodilatory response was unaffected by losartan, an AT(1) receptor antagonist,
      but was inhibited by PD123,319, a selective antagonist of AT(2) receptors. In
      addition, reverse transcriptase-polymerase chain reaction studies revealed high
      amounts of AT(2) receptor mRNA in smooth muscle from these same microvessels. Ang
      II-induced relaxation was inhibited by either tetraethylammonium or iberiotoxin,
      suggesting involvement of the large-conductance, calcium- and voltage-activated
      potassium (BK(Ca)) channel. Subsequent whole-cell and single-channel patch-clamp
      studies on single myocytes demonstrated that Ang II increases the activity of
      BK(Ca) channels. As in our tissue studies, the effect of Ang II on BK(Ca)
      channels was inhibited by PD123,319, but not by losartan. In light of these
      consistent findings from tissue physiology, molecular studies, and
      cellular/molecular physiology, we conclude that Ang II relaxes microvessels via
      stimulation of the AT(2) receptor with subsequent opening of BK(Ca) channels,
      leading to membrane repolarization and vasodilation. These findings provide
      evidence for a novel endothelium-independent vasodilatory effect of Ang II.

PMID- 11230291
TI  - Pulse pressure, aortic reactivity, and endothelium dysfunction in old
      hypertensive rats.
AB  - The reactivity of old hypertensive rat aortas has not been investigated in
      relation to each phenotype of the blood pressure curve, mean arterial pressure
      (MAP), and pulse pressure (PP). Aortic reactivities from 3- to 78-week-old Wistar
      Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were studied with the
      use of organ chambers and invasive blood pressure, carotid diameter, and
      histomorphometry. MAP and PP were elevated in SHR, but at 78 weeks, a selective
      increase of PP without further MAP increase was observed for the same carotid
      diameter as WKY. Aortic relaxation in response to carbamylcholine decreased
      similarly with age in both strains. With (+) or without (-) endothelium (E),
      maximal developed tension (MDT) under KCl increased linearly with age in SHR,
      proportionally to wall thickness and MAP increase. Under norepinephrine (NE), MDT
      of E(-) aortas from SHR and controls increased with age and reached plateaus at
      12 weeks, whereas MDT of E(+) aortas from SHR increased linearly with age.
      Because the NE-induced MDT was higher for E(-) than E(+), the difference
      estimated endothelial function. This difference reached plateaus from 12 to 78
      weeks in WKY but was abolished beyond 12 weeks in SHR, a finding also observed
      under NO-synthase inhibition. In old hypertensive rats, (1) increased KCl
      reactivity is endothelium independent but influenced by the MAP-dependent aortic
      hypertrophy with resulting increased vascular smooth muscle reactivity, whereas
      (2) increased NE reactivity is endothelium dependent in association with
      increased PP, altered endothelial function, and extracellular matrix, with
      resulting enhanced intrinsic arterial stiffness.

PMID- 11230292
TI  - Reduced hypoxic pulmonary vascular remodeling by nitric oxide from the
      endothelium.
AB  - We examined whether overproduction of endogenous nitric oxide (NO) can prevent
      hypoxia-induced pulmonary hypertension and vascular remodeling by using
      endothelial NO-overexpressing (eNOS-Tg) mice. Male eNOS-Tg mice and their
      littermates (wild-type, WT) were maintained in normoxic or 10% hypoxic condition
      for 3 weeks. In normoxia, eNOS protein levels, Ca(2+)-dependent NOS activity, and
      cGMP levels in the lung of eNOS-Tg mice were higher than those of WT mice.
      Activity of eNOS and cGMP production in the lung did not change significantly by
      hypoxic exposure in either genotype. Chronic hypoxia did not induce iNOS
      expression nor increase its activity in either genotype. Plasma and lung
      endothelin-1 levels were increased by chronic hypoxia, but these levels were not
      significantly different between the 2 genotypes. In hemodynamic analysis, right
      ventricular systolic pressure (RVSP) in eNOS-Tg mice was similar to that in WT
      mice in normoxia. Chronic hypoxia increased RVSP and induced right ventricular
      hypertrophy in both genotypes; however, the degrees of these increases were
      significantly smaller in eNOS-Tg mice. Histological examination revealed that
      hypoxic mice showed medial wall thickening in pulmonary arteries. However, the
      increase of the wall thickening in small arteries (diameter <80 microm) by
      chronic hypoxia was inhibited in eNOS-Tg mice. Furthermore, muscularization of
      small arterioles was significantly attenuated in eNOS-Tg mice. Thus, we
      demonstrated directly that overproduction of eNOS-derived NO can inhibit not only
      the increase in RVSP associated with pulmonary hypertension but also remodeling
      of the pulmonary vasculature and right ventricular hypertrophy induced by chronic
      hypoxia.

PMID- 11230294
TI  - Increased levels of 12(S)-HETE in patients with essential hypertension.
AB  - The platelet-type 12-lipoxygenase (12-LO) catalyzes the transformation of
      arachidonic acid into 12-hydroperoxyeicosatetraenoic acid [12-(S)HPETE], which is
      reduced to 12-hydroxyeicosatetraenoic acid [12-(S)HETE]. These metabolites
      exhibit a variety of biological activities such as mediation of angiotensin II
      induced intracellular calcium transients in cultured rat vascular smooth muscle
      cells. It has recently been reported that platelet 12(S)-HETE production is
      enhanced in the spontaneously hypertensive rat. The pronounced hypotensive effect
      of LO inhibition in SHR suggests that LO activity may play a role in this form of
      hypertension. The aim of this study was to determine the basal and thrombin
      induced platelet 12(S)-HETE production and the urinary 12(S)-HETE excretion in
      essential hypertension. We studied 19 patients with this disease (57+/-2 years of
      age) and 9 normotensive control subjects (48+/-5 years of age) (P:=0.074). 12(S)
      HETE was measured in Sep-Pack-extracted samples with specific ELISA and high
      performance liquid chromatography. The platelet basal level of 12(S)-HETE was
      significantly higher in patients than in control subjects (3.56+/-1.22 versus
      0.64+/-0.13 ng/10(6) platelets, P:<0.025). In contrast, there were no differences
      in thrombin-stimulated (1 U/mL) 12(S)-HETE generation: 7.66+/-2.14 in patients
      versus 4.87+/-1.46 in control subjects (P:=0.61). Platelet 12-LO protein levels,
      measured by Western blotting with a polyclonal antibody, were higher in the
      patients than in the control subjects. The urinary excretion of 12(S)-HETE was
      higher in patients than in control subjects: 36.8+/-7.24 versus 17.1+/-3.14 ng/mg
      creatinine (P:<0.01). These results indicate that 12(S)-HETE levels and 12-LO
      protein are increased in patients with essential hypertension, suggesting a role
      for this metabolite in human hypertension.

PMID- 11230293
TI  - Endothelin antagonism uncovers insulin-mediated vasorelaxation in vitro and in
      vivo.
AB  - The endothelial actions of insulin remain an area of intense research because
      they relate to both insulin sensitivity and vascular tone. Physiological doses of
      insulin evoke endothelium-dependent vasorelaxation in humans; however, this
      remains a pharmacological phenomenon in rat aortas. Because insulin may stimulate
      the divergent production of both nitric oxide and endothelin-1, we hypothesized
      that the lack of insulin-induced vasorelaxation at low/subthreshold
      concentrations may be due to the concurrent production of endothelin-1, which in
      turn serves to inhibit nitric oxide-dependent, insulin-mediated dilation. To
      investigate this, we studied the effects of subthreshold concentrations of
      insulin (100 mU/L) on norepinephrine-induced contraction in rat aortas following
      short-term and long-term endothelin blockade. In addition, the effects of
      tetrahydrobiopterin inhibition (with diaminohydroxyprimidine) on norepinephrine
      induced contraction in the presence of insulin and endothelin receptor blockade
      were investigated. Subthreshold concentrations of insulin failed to evoke
      vasorelaxation in rat aortas. Strikingly, short-term endothelin A/B receptor
      blockade with bosentan (10(-2) mmol/L) uncovered insulin-mediated dilation; the
      percent maximum contraction and sensitivity of aortas to norepinephrine were
      attenuated (% maximum relaxation: bosentan+insulin 74+/-4%* versus bosentan 92+/
      3%, insulin 107+/-5% P:<0.002; pD(2) values: bosentan+insulin 6.87+/-0.14* versus
      bosentan 7.40+/-0.15, insulin 7.63+/-0.11, *P:<0.002). This effect was mediated
      through endothelin A receptors because bosentan and BQ-123 (10(-2) mmol/L)
      attenuated norepinephrine-induced contraction to a similar degree. In addition,
      insulin evoked vasorelaxation in aortas isolated from rats after long-term
      bosentan treatment (100 mg. kg(-1). d(-1), 3 weeks). The component of insulin
      mediated vasorelaxation uncovered by endothelin receptor blockade was
      tetrahydrobiopterin-dependent because it was reversed by diaminohydroxyprimidine.
      These data demonstrate, for the first time, the functional interaction between
      insulin, endothelin-1, and tetrahydrobiopterin in modulating vascular tone in rat
      aortas in vitro and in vivo.

PMID- 11230297
TI  - Role of angiotensin and its inhibition in hypertension, ischemic heart disease,
      and heart failure.
AB  - This is a personal historical account relating the events that led to the first
      application of angiotensin inhibition (either by ACE inhibitors or by angiotensin
      receptor blockade) to the investigation of the pathogenesis and treatment of
      hypertension, ischemic heart disease, and heart failure. Included are animal
      experiments, clinical observations, and the earliest clinical experimental
      studies that helped define some of the detrimental effects of angiotensin II and
      the beneficial hemodynamic results of its inhibition, which have been
      subsequently corroborated and amplified by large randomized outcome trials.

PMID- 11230298
TI  - Left ventricle and arteries: structure, function, hormones, and disease.
AB  - The observation in the 1970s that the performance of the dysfunctional left
      ventricle was under the influence of aortic impedance led us to exploration of
      the role of the renin-angiotensin system and other hormonal systems in the
      progression of heart failure. The apparent efficacy of vasodilator drugs led to
      the first randomized, controlled trial in heart failure that demonstrated that
      all impedance-lowering drugs did not exert the same long-term benefit.
      Differences on the structural remodeling process in the myocardium and arterial
      vasculature were shown to account for the differential long-term response. We now
      recognize that the remodeling process in the left ventricle may be inhibited by
      nitrates, converting enzyme inhibitors, and beta-blockers, and this growth
      process leads to adverse outcomes. The impedance load on the left ventricle is
      influenced by vascular remodeling that also may be inhibited by drugs such as
      converting enzyme inhibitors. Thus, progression of cardiovascular disease is
      largely a consequence of structural changes that are hormonally mediated and may
      be inhibited by drug therapy.

PMID- 11230299
TI  - Twins in cardiovascular genetic research.
AB  - Twin studies have been largely responsible for showing the effects of genetic
      variance on a quantitative trait. The model is based on the fact that monozygotic
      twins share all genes in common, whereas dizygotic twins are related as siblings
      and share "on average" half their genes. Environmental confounders are minimized
      because twin children are usually exposed to similar environments. Blood pressure
      was first shown to be heritable in a twin study. However, intermediary
      phenotypes, such as components of the renin-angiotensin system, sympathetic
      nervous system, renal function, and the facility in excreting electrolytes, are
      also heritable. The advent of molecular genetics has made twin studies more
      useful than ever because of the power of quantitative trait loci analyses.
      Recruitment of the parents of dizygotic twins greatly facilitates this effort.
      Gene loci linked to blood pressure, intermediate phenotypes, cardiac dimensions,
      lipid concentrations, and even components of the ECG have been identified. The
      use of single-nucleotide polymorphisms then allows for novel association
      approaches within the cohort. Twin studies will continue to gain in importance
      and utility, particularly in elucidating normal human genetic diversity.

PMID- 11230300
TI  - The future of hypertension therapy: sense, antisense, or nonsense?
AB  - Hypertension is a debilitating disease with significant socioeconomic and
      emotional impact. Despite recent success in the development of traditional
      pharmacotherapy for the management of hypertension, the incidence of this disease
      is on the rise and has reached epidemic proportions by all estimates. This has
      led many to conclude that traditional pharmacotherapy has reached an intellectual
      plateau, and novel approaches for the treatment and control of hypertension must
      be explored. We have begun to investigate the possibility of treating and/or
      curing hypertension by using genetic means. In this review, we will provide
      evidence in favor of targeting of the renin-angiotensin system by antisense gene
      therapy as an effective strategy for the lifelong prevention of hypertension in
      the spontaneously hypertensive rat model. In addition, we will discuss the
      properties of an ideal vector for the systemic delivery of genes and the
      potential experimental hurdles that must be overcome to take this innovative
      approach to the next level of evaluation.

PMID- 11230301
TI  - Antisense inhibition of thyrotropin-releasing hormone reduces arterial blood
      pressure in spontaneously hypertensive rats.
AB  - Thyrotropin-releasing hormone (TRH) plays an important role in central
      cardiovascular regulation. Recently, we described that the TRH precursor gene
      overexpression induces hypertension in the normal rat. In addition, we published
      that spontaneously hypertensive rats (SHR) have central extrahypothalamic TRH
      hyperactivity with increased TRH synthesis and release and an elevated TRH
      receptor number. In the present study, we report that intracerebroventricular
      antisense (AS) treatment with a phosphorothioate oligonucleotide against the TRH
      precursor gene significantly diminished up to 72 hours and in a dose-dependent
      manner the increased diencephalic TRH content, whereas normalized systolic blood
      pressure (SABP) was present in the SHR compared with Wistar-Kyoto (WKY) rats.
      Although basal thyrotropin was higher in SHR compared with WKY rats and this
      difference disappeared after antisense treatment, no differences were observed in
      plasma T4 or T3 between strains with or without AS treatment, indicating that the
      effect of the AS on SABP was independent of the thyroid status. Because the
      encephalic renin-angiotensin system seems to be crucial in the development and/or
      maintenance of hypertension in SHR, we investigated the effect of antisense
      inhibition of TRH on that system and found that TRH antisense treatment
      significantly diminished the elevated diencephalic angiotensin II (Ang II)
      content in the SHR without any effect in control animals, suggesting that the Ang
      II system is involved in the TRH cardiovascular effects. To summarize, the
      central TRH system seems to be involved in the etiopathogenesis of hypertension
      in this model of essential hypertension.

PMID- 11230302
TI  - Antisense inhibition of brain renin-angiotensin system decreased blood pressure
      in chronic 2-kidney, 1 clip hypertensive rats.
AB  - The systemic renin-angiotensin system (RAS) plays an important role in blood
      pressure (BP) regulation during the development of 2-kidney, 1 clip (2K1C)
      hypertension. Its contributions decrease with time after constriction of the
      renal artery. During the chronic phase, the peripheral RAS returns to normal, but
      the hypertension is sustained for months. We hypothesized that in this phase the
      brain RAS contributes to the maintenance of high BP. To test the hypothesis, we
      studied the role of brain RAS by decreasing the synthesis of angiotensinogen
      (AGT) and the angiotensin II (Ang II) type 1a receptor (AT(1)R) with
      intracerebroventricular injections of antisense oligonucleotides (AS-ODNs). The
      response of systolic BP (SBP) to AS-ODNs to AGT mRNA was studied in 2K1C rats at
      6 months after clipping, and the response to AS-ODNs to AT(1)R mRNA was studied
      at 10 months after clipping. Intracerebroventricular injection of AS-ODN-AGT (200
      microgram/kg, n=5) significantly decreased SBP (-22+/-6 mm Hg, P<0.05) compared
      with the sense ODN (n=5) and saline (n=3) groups. Intracerebroventricular
      injection of AS-ODN-AGT reduced the elevated hypothalamic Ang II level. The
      hypothalamic Ang II content in sense ODN and saline groups was significantly
      (P<0.05) higher than in the nonclipped group. Compared with inverted ODN,
      intracerebroventricular injection of AS-ODN-AT(1)R (250 microgram/kg, n=6)
      significantly decreased SBP (-26+/-8 mm Hg, P<0.05) for 3 days after injection.
      This was a brain effect because intravenous AS-ODN-AT(1)R at a dose of 250 to 500
      microgram/kg did not affect SBP. These results suggest that the brain RAS plays
      an important role in maintaining the elevated SBP in chronic 2K1C hypertension.

PMID- 11230303
TI  - Attenuation of hypertension and heart hypertrophy by adeno-associated virus
      delivering angiotensinogen antisense.
AB  - Angiotensinogen (AGT), one of the major components in the renin-angiotensin
      system, has been linked to hypertension in humans and animals. We have previously
      systemically administered antisense oligonucleotides and plasmid vectors with DNA
      that targeted AGT and attenuated hypertension in spontaneously hypertensive rats.
      The aim of the present study was to prolong the effect of antisense treatment by
      the use of a recombinant adeno-associated viral (rAAV) vector targeted to AGT.
      Using a model of lifelong hypertension in which 5-day-old spontaneously
      hypertensive rats are treated, a single intracardiac injection of rAAV-AGT
      antisense (rAAV-AGT-AS) delayed the onset of hypertension for 91 days and
      significantly attenuated hypertension in adulthood for up to 6 months. Systolic
      blood pressure was always lower, by up to 23 mm Hg in the AS-treated group. The
      vector was stable and expressed a reporter gene in liver, kidney, and heart. The
      rAAV-AGT-AS treatment significantly decreased left ventricular hypertrophy
      (P=0.01) and also lowered levels of AGT in the liver (2.78+/-0.61 microgram/g
      tissue versus 5.23+/-0.41 microgram/g tissue for the sense-treated group,
      P<0.01). Measurement of liver transaminases showed no evidence for liver
      toxicity. We conclude that rAAV-AGT-AS offers a safe, stable approach for gene
      therapy of hypertension.

PMID- 11230304
TI  - Telomere length as an indicator of biological aging: the gender effect and
      relation with pulse pressure and pulse wave velocity.
AB  - Chronological age is the primary determinant of stiffness of central arteries.
      Increased stiffness is an independent indicator of cardiovascular risk. The aim
      of this study was to determine whether telomere length, a possible index of
      biological aging, provides a better account than chronological age for variation
      in arterial stiffness, evaluated by measuring pulse pressure and aortic pulse
      wave velocity. The study population included 193 French subjects (120 men, 73
      women), with a mean age of 56+/-11 years, who were not on any antihypertensive
      medications. Telomere length was evaluated in white blood cells by measuring the
      mean length of the terminal restriction fragments. Age-adjusted telomere length
      was longer in women than in men (8.67+/-0.09 versus 8.37+/-0.07 kb; P=0.016). In
      both genders, telomere length was inversely correlated with age (P<0.01).
      Multivariate analysis showed that in men, but not in women, telomere length
      significantly contributed to pulse pressure and pulse wave velocity variations.
      In conclusion, telomere length provides an additional account to chronological
      age of variations in both pulse pressure and pulse wave velocity among men, such
      that men with shorter telomere length are more likely to exhibit high pulse
      pressure and pulse wave velocity, which are indices of large artery stiffness.
      The longer telomere length in women suggests that for a given chronological age,
      biological aging of men is more advanced than that of women.

PMID- 11230305
TI  - Renin gene transfer restores angiogenesis and vascular endothelial growth factor
      expression in Dahl S rats.
AB  - In a previous study, we demonstrated that Dahl S rats (SS group) have low plasma
      renin activity, whereas transfer of a region of chromosome 13 containing the
      renin gene from Dahl R onto a congenic strain of Dahl SS/Jr/Hsd/MCW rats
      (S/ren(RR) group) restores renin secretory responses. In the present study, we
      compared the angiogenic responses to electrical stimulation in the SS and
      S/ren(RR) groups to explore the hypotheses that the renin-angiotensin system is
      involved in vascular endothelial growth factor (VEGF) expression and angiogenesis
      in skeletal muscle. Congenic SS and S/ren(RR) rats fed a 0.4% or 4% salt diet
      were surgically prepared by chronic implantation of an electrical stimulator.
      Another group of S/ren(RR) rats was treated with lisinopril 2 days before the
      surgery and throughout the stimulation protocol. The right tibialis anterior (TA)
      and extensor digitorum longus (EDL) were stimulated for 8 hours per day for 7
      days. The contralateral muscles served as controls. Western blot analysis was
      performed to identify VEGF protein expression in these muscles. Electrical
      stimulation produced no change in vessel density of the SS group fed a 0.4% salt
      diet (change 5.50% and 8.14% for EDL and TA, respectively). Transfer of a region
      containing the renin gene restored the angiogenic response (change 16% and 30%
      for EDL and TA, respectively) despite a significantly higher blood pressure.
      Blockade of the renin-angiotensin system by lisinopril or high salt restored the
      responses observed in the SS group fed a low salt diet. In addition, increases in
      VEGF expression to electrical stimulation were observed only in the S/ren(RR)
      group fed a low salt diet. These results suggest that renin gene transfer
      restores angiogenesis and VEGF expression in the skeletal muscle of Dahl S rats.

PMID- 11230306
TI  - Reciprocal consomic strains to evaluate y chromosome effects.
AB  - We have previously demonstrated that the SHRSP Y chromosome contains a locus that
      contributes to hypertension in SHRSP/WKY F2 hybrids and that SHRSP exhibit an
      increased vulnerability to focal cerebral ischemia after permanent middle
      cerebral artery occlusion (MCAO). This increased vulnerability is inherited as a
      codominant trait, and a putative role for the Y chromosome has been suggested in
      F1 hybrids. The objective of this study was to investigate further the role of Y
      chromosome in blood pressure (BP) regulation and in the vulnerability to cerebral
      ischemia. We have constructed consomic strains by selectively replacing the Y
      chromosome from WKY rats with that of SHRSP, and vice versa, by using a marker
      assisted breeding strategy. Permanent MCAO was carried out by electrocoagulation,
      with infarct volume expressed as a percentage of the ipsilateral hemisphere.
      Systolic blood pressure was measured by radiotelemetry during a baseline period
      of 5 weeks followed by a 3-week period of salt loading. We observed that the
      transfer of the Y chromosome from WKY onto SHRSP background significantly reduced
      systolic BP in consomic strains, SP.WKYGlaY(w) (n=6) versus SHRSP (n=6) (209.2+/
      10.4 mm Hg versus 241.7+/-7.7 mm Hg, F=5.88, P=0.038) during the salt-loading
      period. In the reciprocal consomic strain, WKY.SPGlaY(s) (n=5), systolic BP was
      increased compared with WKY parental strain (n=6) (147.6+/-2.4 mm Hg versus
      132.6+/-5.1 mm Hg, F=6.11, P=0.035) during baseline. Infarct volumes in consomic
      strains were not significantly different from their respective parental strain:
      WKY.SPGlaY(s) (n=7) versus WKY (n=7), 22.8+/-3.7% versus 22.2+/-8.0%, 95% CI=
      12.7, 4.2, P=0.3; SP.WKYGlaY(w) (n=7) versus SHRSP (n=6), 37.7+/-4.4% versus
      33.6+/-7.6%, 95% CI=-20.3, 12.1, P=0.5. We conclude that the SHRSP Y chromosome
      harbors a locus contributing to systolic BP, whereas no contribution to
      vulnerability to cerebral ischemia can be detected.

PMID- 11230307
TI  - Sodium-lithium countertransport activity is linked to chromosome 5 in baboons.
AB  - The genes involved in the regulation of cellular sodium transport
      characteristics, which are correlated with some forms of essential hypertension,
      have not yet been identified. We are studying the genes and environmental factors
      that affect red blood cell sodium-lithium countertransport (SLC) activity and
      intracellular sodium (ICNa) concentration in 634 baboons that comprise 11
      pedigrees of 2 and 3 generations each. To detect and locate possible quantitative
      trait loci (QTLs) that affect SLC activity and ICNa concentration, we performed a
      genome screen by using a maximum likelihood-based variance-components linkage
      analysis program (SOLAR). SLC and ICNa phenotypes as well as genotypes on 281
      microsatellite loci were available for all pedigreed animals. Both SLC and ICNa
      traits were highly heritable (residual heritability 0.593+/-0.083 [P<0.0001] and
      0.739+/-0.082 [P<0.0001], respectively). We obtained evidence that a possible QTL
      for SLC activity is located on the baboon homologue of human chromosome 4 between
      D4S2456 and D4S2365 with a maximum multipoint lod score of 9.3 (P<10(-)(10)) near
      D4S1645. This QTL accounts for approximately two thirds of the total additive
      genetic variation in SLC activity in baboons. Although ICNa concentration was
      highly heritable, we found no evidence for linkage to a QTL with use of this
      methodology. Thus, we have evidence that a gene located on the baboon homologue
      of human chromosome 4 (baboon chromosome 5) affects cell sodium transport in
      baboons.

PMID- 11230308
TI  - Paradoxical regulation of short promoter human renin transgene by angiotensin ii.
AB  - We previously reported the generation of transgenic mice containing the entire
      human renin gene with a 900-bp promoter. To determine whether all the required
      elements for angiotensin II-mediated suppression of human renin are present in
      these mice, angiotensin II was chronically infused by means of osmotic minipump
      at both low and high doses, 200 and 1000 ng/kg per minute, respectively. Blood
      pressure was measured by tail-cuff, and kidney renin mRNA levels were quantitated
      using ribonuclease protection assays. Blood pressure was unchanged in mice
      receiving either vehicle or low-dose angiotensin II infusion but was increased by
      approximately 40 mm Hg with the higher dose of angiotensin II. Mouse renin mRNA
      decreased by >60% during both pressor and nonpressor angiotensin II infusion.
      Human renin mRNA was not suppressed by nonpressor angiotensin II and was
      paradoxically increased 1.9-fold by pressor angiotensin II. The lack of
      upregulation during nonpressor angiotensin II suggested that the increase might
      be pressure-mediated. To test this, the angiotensin II-induced increase in blood
      pressure was prevented by coadministration of the vasodilator, hydralazine (15
      mg/kg per day). Hydralazine alone decreased blood pressure (-27+/-3 mm Hg) and
      increased mouse renin mRNA 2.4-fold. Human renin mRNA was unresponsive to this
      vasodilator-induced fall in pressure and despite the normalization of blood
      pressure by hydralazine, high-dose angiotensin II still caused a 2.1-fold
      increase in human renin mRNA. Thus, the first 900 bp of the human renin promoter
      does not contain all the elements required for appropriate angiotensin II
      mediated suppression of human renin mRNA.

PMID- 11230309
TI  - Alterations in blood pressure and heart rate variability in transgenic rats with
      low brain angiotensinogen.
AB  - To study whether the brain renin-angiotensin system plays a role in the long-term
      and short-term control of blood pressure and heart rate variability, we examined
      in transgenic rats [TGR(ASrAOGEN)] with low brain angiotensinogen levels the 24
      hour variation of blood pressure and heart rate. Telemetry recordings were made
      during basal and hypertensive conditions induced by a low-dose subcutaneous
      infusion of angiotensin II for 7 days. Short-term blood pressure and heart rate
      variability were evaluated by spectral analysis, and as a measure of baroreflex
      sensitivity, the average transfer gain between the pressure and heart rate
      variations was calculated. During the angiotensin II infusion in control but not
      TGR(ASrAOGEN) rats, the 24-hour rhythm of blood pressure was inverted (5.8+/-2
      versus -0.4+/-1.8 mm Hg/group of day-night differences of blood pressure, P<0.05,
      respectively). In both the control and TGR(ASrAOGEN) rats, the 24-hour heart rate
      rhythms remained unaltered and paralleled those of locomotor activity. The
      transfer gain between 0.3 to 0.6 Hz was significantly higher in TGR(ASrAOGEN)
      than in control rats during control (0.71+/-0.1 versus 0.35+/-0.06, P<0.05) but
      not during angiotensin II infusion (0.6+/-0.07 versus 0.4+/-0.1, P>0.05). These
      results demonstrate that the brain renin-angiotensin system plays an important
      role in mediating the effects of angiotensin II on the circadian variation of
      blood pressure. Furthermore, these data indicate that a permanent deficiency in
      the brain renin-angiotensin system alters the reflex control of heart rate in
      rats.

PMID- 11230310
TI  - Endothelial dysfunction and xanthine oxidoreductase activity in rats with human
      renin and angiotensinogen genes.
AB  - We examined whether xanthine oxidoreductase (XOR), a hypoxia-inducible enzyme
      capable of generating reactive oxygen species, is involved in the onset of
      angiotensin (Ang) II-induced vascular dysfunction in double-transgenic rats
      (dTGR) harboring human renin and human angiotensinogen genes. In 7-week-old
      hypertensive dTGR, the endothelium-mediated relaxation of noradrenaline (NA)
      precontracted renal arterial rings to acetylcholine (ACh) in vitro was markedly
      impaired compared with Sprague Dawley rats. Preincubation with superoxide
      dismutase (SOD) improved the endothelium-dependent vascular relaxation,
      indicating that in dTGR, endothelial dysfunction is associated with increased
      superoxide formation. Preincubation with the XOR inhibitor oxypurinol also
      improved endothelium-dependent vascular relaxation. The endothelium-independent
      relaxation to sodium nitroprusside was similar in both strains. In dTGR, serum 8
      isoprostaglandin F(2alpha), a vasoconstrictor and antinatriuretic arachidonic
      acid metabolite produced by oxidative stress, was increased by 100%, and the
      activity of XOR in the kidney was increased by 40%. Urinary nitrate plus nitrite
      (NO(x)) excretion, a marker of total body NO generation, was decreased by 85%.
      Contractile responses of renal arteries to Ang II, endothelin-1 (ET-1), and NA
      were decreased in dTGR, suggesting hypertension-associated generalized changes in
      the vascular function rather than a receptor-specific desensitization. Valsartan
      (30 mg/kg PO for 3 weeks) normalized blood pressure, endothelial dysfunction, and
      the contractile responses to ET-1 and NA. Valsartan also normalized serum 8
      isoprostaglandin F(2alpha) levels, renal XOR activity, and, to a degree, NO(x)
      excretion. Thus, overproduction of Ang II in dTGR induces pronounced endothelial
      dysfunction, whereas the sensitivity of vascular smooth muscle cells to nitric
      oxide is unaltered. Ang II-induced endothelial dysfunction is associated with
      increased oxidative stress and vascular xanthine oxidase activity.

PMID- 11230311
TI  - Nuclear factor 1 is a negative regulator of gadd153 gene expression in vascular
      smooth muscle cells.
AB  - Growth arrest and DNA damage inducible gene 153 (gadd153) is expressed at very
      low levels in growing cells but is markedly induced in response to cellular
      stresses, including glucose deprivation, exposure to genotoxic agents, and other
      growth-arresting situations. Forced expression of GADD153 can induce cell cycle
      arrest and/or apoptosis in many types of cells. Recently, we reported that
      GADD153 was induced in vascular smooth muscle cells (VSMCs) in neointimal lesions
      of balloon-injured carotid arteries. To investigate the underlying molecular
      mechanisms of gadd153 gene expression in VSMCs, we isolated and characterized a
      promoter region of the rat gadd153 gene. Sequence alignments of this region
      revealed 1 TATA-like sequence and several well-known cis elements. The 5'
      deletion analysis for this region showed that a domain spanning -447 through -368
      drastically reduced the promoter activity to almost equal levels of promoterless
      control. Because this domain contained a consensus sequence for the nuclear
      factor 1 family of proteins (NF1), DNA-binding studies were performed by use of 2
      types of NF1 consensus probes. Both probes were specifically shifted by nuclear
      extracts from proliferating VSMCs and were supershifted by antiserum against
      CCAAT transcription factor/NF1. In addition, promoter activity of a mutant
      luciferase vector, which was generated by a point mutation at the NF1 binding
      motif of the gadd153 gene, was 14-fold higher than that of a wild-type one. These
      results suggest that gadd153 gene expression in VSMCs is negatively regulated by
      an NF1-binding motif, and NF1 may act as an antiapoptotic factor by continuously
      suppressing gadd153 gene expression in growing VSMCs.

PMID- 11230312
TI  - Genome-wide linkage analysis of pulse pressure in Mexican Americans.
AB  - Pulse pressure, a measure of aortic stiffness, is a strong predictor of
      cardiovascular mortality. To locate genes that affect pulse pressure, we
      performed genetic analysis on randomly ascertained families in the San Antonio
      Family Heart Study. Pulse pressure was defined as the difference between systolic
      and diastolic blood pressures. Likelihood methods were used to construct a model
      that had both single-locus and polygenic components for 46 families (1308
      individuals). The single-locus component included sex-specific and genotype
      specific effects of both age and body mass index. Using this model, we then
      performed 2-point linkage analysis in 10 families (440 individuals) that were
      among the largest of the 46 families and that had been genotyped for 399
      polymorphic markers. The model that contained only the polygenic component and
      simple effects of the covariates showed pulse pressure heritability of 0.21. When
      the single-locus component was added, the sex-specific and genotype-specific
      effects of age and body mass index were highly significant (P<0.002). The full
      model accounted for 73% of the total variation of pulse pressure. Linkage
      analysis using this model with each marker revealed 4 markers with lod scores
      >1.9, which is the Lander-Kruglyak suggestive linkage standard. D21S1440 had a
      lod score of 2.78 with a recombination fraction (theta) of 0.02. D7S1799 had a
      lod score of 2.04 (theta=0.01), D8S1100 had a lod score of 1.98 (theta=0.08), and
      D18S844 had a lod score of 1.95 (theta=0.11). These results are highly correlated
      with results involving systolic blood pressure, indicating that pulse pressure
      may not be genetically distinct from systolic blood pressure.

PMID- 11230313
TI  - Salt sensitivity, pulse pressure, and death in normal and hypertensive humans.
AB  - Although factors such as age, blood pressure, and its responsiveness to changes
      in sodium balance and extracellular fluid volume status (salt sensitivity) are
      associated with an increased risk of end-organ disease and cardiovascular events
      in hypertensive subjects, no such relationship with mortality has been
      demonstrated for salt sensitivity in normotensive subjects. We conducted long
      term follow-up of 430 normal and 278 hypertensive subjects in whom assessment of
      salt sensitivity of blood pressure was performed as long as 27 years ago. We
      ascertained the status of 596 subjects (85% of the total population), 123 (21%)
      of whom had died. The following initial measurements were significantly (P<0.002)
      associated with subjects who had died compared with subjects known to be alive:
      age at study, pulse pressure, systolic, diastolic, and mean arterial pressures,
      hypertension, salt sensitivity, baseline renin levels, and body mass index (but
      not body weight). A stepwise logistic regression found the following independent
      predictors of death (odds ratio, 95% CI): age at initial study (1.08, 1.06 to
      1.10), baseline blood pressure (1.03, 1.01 to 1.04), sodium sensitivity (1.73,
      1.02 to 2.94), and male gender (1.91, 1.15 to 3.17). When survival curves were
      examined, normotensive salt-sensitive subjects aged >25 years when initially
      studied were found to have a cumulative mortality similar to that of hypertensive
      subjects, whereas salt-resistant normotensive subjects had increased survival
      (P:<0.001). These observations provide unique evidence of a relationship between
      salt sensitivity and mortality that is independent of elevated blood pressure.

PMID- 11230314
TI  - Endothelial dysfunction and salt-sensitive hypertension in spontaneously diabetic
      Goto-Kakizaki rats.
AB  - Endothelial dysfunction is associated with hypertension, hypercholesterolemia,
      and heart failure. We tested the hypothesis that spontaneously diabetic Goto
      Kakizaki (GK) rats, a model for type 2 diabetes, exhibit endothelial dysfunction.
      Rats also received a high-sodium diet (6% NaCl [wt/wt]) and chronic angiotensin
      type 1 (AT(1)) receptor blockade (10 mg/kg PO valsartan for 8 weeks). Compared
      with age-matched nondiabetic Wistar control rats, GK rats had higher blood
      glucose levels (9.3+/-0.5 versus 6.9+/-0.2 mmol/L for control rats), 2.7-fold
      higher serum insulin levels, and impaired glucose tolerance (all P<0.05).
      Telemetry-measured mean blood pressure was 15 mm Hg higher in GK rats (P<0.01)
      compared with control rats, whereas heart rates were not different. Heart weight-
      and kidney weight-to-body weight ratios were higher in GK rats (P<0.05), and 24
      hour albuminuria was increased 50%. Endothelium-mediated relaxation of
      noradrenaline-precontracted mesenteric arterial rings by acetylcholine was
      impaired compared with the control condition (P<0.05), whereas the sodium
      nitroprusside-induced relaxation was similar. Preincubation of the arterial rings
      with the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester and the
      cyclooxygenase inhibitor diclofenac inhibited relaxations to acetylcholine almost
      completely in GK rats but not in Wistar rats, suggesting that endothelial
      dysfunction can be in part attributed to reduced relaxation via arterial K(+)
      channels. Perivascular monocyte/macrophage infiltration and intercellular
      adhesion molecule-1 overexpression were observed in GK rat kidneys. A high-sodium
      diet increased blood pressure by 24 mm Hg and 24-hour albuminuria by 350%,
      induced cardiac hypertrophy, impaired endothelium-dependent relaxation further,
      and aggravated inflammation (all P<0.05). The serum level of 8-isoprostaglandin
      F(2alpha), a vasoconstrictor and antinatriuretic arachidonic acid metabolite
      produced by oxidative stress, was increased 400% in GK rats on a high-sodium
      diet. Valsartan decreased blood pressure in rats fed a low-sodium diet and
      prevented the inflammatory response. In rats fed a high-sodium diet, valsartan
      did not decrease blood pressure or improve endothelial dysfunction but protected
      against albuminuria, inflammation, and oxidative stress. As measured by
      quantitative autoradiography, AT(1) receptor expression in the medulla was
      decreased in GK compared with Wistar rats, whereas cortical AT(1) receptor
      expression, medullary and cortical angiotensin type 2 (AT(2)) receptor
      expressions, and adrenal ACE and neutral endopeptidase expressions were
      unchanged. A high-sodium diet did not influence renal AT(1), AT(2), ACE, or
      neutral endopeptidase expressions. In valsartan-treated GK rats, the cortical and
      medullary AT(1) receptor expressions were decreased in the presence and absence
      of a high-sodium diet. A high-sodium diet increased plasma brain natriuretic
      peptide concentrations in presence and absence of valsartan treatment. We
      conclude that hypertension in GK rats is salt sensitive and associated with
      endothelial dysfunction and perivascular inflammation. AT(1) receptor blockade
      ameliorates inflammation during a low-sodium diet and partially protects against
      salt-induced vascular damage by blood pressure-independent mechanisms.

PMID- 11230315
TI  - Degeneration of capsaicin-sensitive sensory nerves leads to increased salt
      sensitivity through enhancement of sympathoexcitatory response.
AB  - We have previously shown that neonatal degeneration of capsaicin-sensitive
      sensory nerves renders a rat responsive to a salt load with an increase in blood
      pressure and a decrease in natriuretic response. To test the hypothesis that the
      enhanced sympathoexcitatory response to a high salt intake contributes to the
      development of hypertension in this model, newborn Wistar rats were given 50
      mg/kg capsaicin and/or 80 mg/kg guanethidine subcutaneously. Control rats were
      treated with vehicle. After the weaning period, male rats were grouped as the
      following and given a high sodium diet (4%) for 2 weeks: capsaicin and
      guanethidine coadministration (CAP-GUA), capsaicin only (CAP), guanethidine only
      (GUA), and vehicle control (CON). Norepinephrine concentrations in the atrium
      were significantly lower in CAP-GUA and GUA than in CON rats (P<0.05). Twenty
      four-hour urine and sodium excretions were significantly lower in CAP than in CAP
      GUA, GUA, and CON rats (P<0.05). Mean arterial pressure (mm Hg) was significantly
      higher in CAP (180+/-10) than in CAP-GUA (106+/-1), GUA (133+/-5), and CON (122+/
      3) rats (P<0.05). Thus, sympathectomy restores the natriuretic response to a high
      salt intake and prevents the development of salt-sensitive hypertension induced
      by sensory denervation. These data indicate that sensory nerves counterbalance
      the prohypertensive effect of the sympathetic nerves to maintain blood pressure
      within normal range during salt loading.

PMID- 11230316
TI  - Endothelial dysfunction in salt-sensitive essential hypertension.
AB  - The aim of this study was to evaluate endothelium-dependent and -independent
      vasodilation, as well as endothelium biochemical markers, in a group of essential
      hypertensive patients classified on the basis of salt sensitivity. Changes in
      forearm blood flow in response to acetylcholine, sodium nitroprusside, and N(G)
      monomethyl-L-arginine (L-NMMA) infusion were determined by means of strain-gauge
      plethysmography. Moreover, plasma and urinary concentrations of nitrates, cGMP,
      and endothelin were measured during low (50 mmol/d) and high (250 mmol/d) salt
      intake. Salt-sensitive hypertension was diagnosed in 26 patients who exhibited a
      significant increase in 24-hour mean blood pressure assessed by ambulatory blood
      pressure monitoring after 1 week of high salt intake. Nineteen patients were
      considered salt resistant. Compared with salt-resistant hypertensives, salt
      sensitive patients presented a significant lower (P=0.005) maximal acetylcholine
      induced vasodilation (21+/-6.3 versus 28+/-7.5 mL. 100 mL(-1). tissue. min(-1)).
      On the contrary, maximal sodium nitroprusside-induced vasodilation did not
      significantly differ between groups (22.4+/-4.5 versus 23.9+/-5.3 mL. 100 mL(-1).
      tissue. min(-1)). The decrease in maximal acetylcholine-induced vasodilation
      promoted by the coadministration of L-NMMA was significantly more pronounced in
      salt-resistant compared with salt-sensitive patients (P=0.003). Finally, high
      salt intake promoted a significant decrease in 24-hour urinary nitrate excretion
      in salt-sensitive patients (from 443+/-54 to 312+/-54 micromol/d; P=0.033)
      compared with salt-resistant hypertensives (from 341+/-50 to 378+/-54
      micromol/d). We conclude that salt-sensitive hypertension is associated with
      endothelial dysfunction characterized by a defective endothelium-dependent
      vasodilation. Impairment of the L-arginine-nitric oxide pathway may be
      responsible for this abnormal endothelial response.

PMID- 11230317
TI  - Identification of peptides that target the endothelial cell-specific LOX-1
      receptor.
AB  - Current gene delivery vectors demonstrate inefficient and nonselective gene
      transfer to vascular endothelial cells, limiting their use in cardiovascular gene
      transfer and therapy. The lectinlike oxidized LDL receptor (LOX-1) is expressed
      selectively at low levels on endothelial cells but is strongly upregulated in
      dysfunctional endothelial cells associated with hypertension and atherogenesis.
      Using LOX-1 as a target receptor, we have sought to isolate peptide ligands that
      mediate binding to the extracellular domain of LOX-1 as a definitive step in the
      development of targeted gene transfer aimed at dysfunctional endothelium. To
      achieve this, we ectopically overexpressed LOX-1 in cells lacking endogenous LOX
      1 by using an episomally maintained expression system and designed a novel
      subtractive phage display strategy to identify peptides selective for LOX-1.
      After extensive biopanning, we sequenced individual phage and identified 60 novel
      peptides. This population of peptides contained a number of potential consensus
      motifs. To define the selectivity of individual peptides for LOX-1 with the use
      of an independent gene transfer system, we developed a novel adenoviral vector to
      overexpress LOX-1 transiently in primary cells and cell lines. We then quantified
      recovery of each peptide from LOX-1-positive and LOX-1-negative cells after
      adenovirus-mediated gene transfer. This strategy confirmed selectivity to LOX-1
      for many peptides and highlighted the peptides LSIPPKA, FQTPPQL, and LTPATAI as
      principal candidates. These peptides will be useful for the selective targeting
      of viral and nonviral gene transfer vectors to endothelial cells expressing the
      LOX-1 receptor in vitro and in vivo and in particular dysfunctional endothelial
      cells associated with hypertension and atherosclerosis.

PMID- 11230319
TI  - Marinobufagenin, an endogenous alpha-1 sodium pump ligand, in hypertensive Dahl
      salt-sensitive rats.
AB  - Dahl salt-sensitive rats (DS), which have a mutation in the alpha-1 subunit of
      Na(+)/K(+)-ATPase, exhibit impaired pressure natriuresis and on a high-salt diet,
      retain Na(+) and exhibit increased blood pressure. Recently, we have shown that
      mammalian tissues contain a bufadienolide Na(+)/K(+)-ATPase inhibitory factor,
      marinobufagenin (MBG), that exhibits greater affinity for the alpha-1 than alpha
      3 sodium pump isoform. The present study investigated the possible role of MBG in
      hypertension in DS on a high NaCl intake. Eight DS and 8 Dahl salt-resistant rats
      (DR) were placed on an 8% NaCl diet. Within 2 weeks, systolic blood pressure
      increased in DS (162+/-9 mm Hg at week 2 versus 110+/-2 mm Hg in baseline,
      P<0.01), and increased less in DR (124+/-3 mm Hg at week 2 versus 112+/-2 mm Hg
      in baseline). Renal excretion of MBG increased 4-fold (38.9+/-7.6 pmol versus
      9.1+/-1.3 pmol in baseline, P<0.01) in DS, but by only 25% in DR (13.2+/-0.9 pmol
      versus 10.3+/-0.7 pmol in baseline). Excretion of endogenous ouabain did not
      change in either strain. MBG-immunoreactive material was purified from the urine
      of hypertensive DS by means of 2 steps of reverse-phase high performance liquid
      chromatography (HPLC) and compared with plant ouabain and amphibian MBG for its
      ability to inhibit the Na(+)/K(+)-ATPase from rat kidney (which expresses only
      alpha-1 Na(+)/K(+)-ATPase isoform). Unlike ouabain (IC(50)=248 micromol/L),
      serially diluted, HPLC-purified MBG immunoreactivity from DS and authentic MBG
      potently inhibited rat kidney Na(+)/K(+)-ATPase (IC(50)=70 and 78 nmol/L,
      respectively). Our results suggest that an alpha-1 Na(+)/K(+)-ATPase ligand, MBG,
      is elaborated to promote natriuresis in hypertensive DS. MBG acts as a selective
      inhibitor of the ouabain-resistant alpha-1 Na(+)/K(+)-ATPase subunit, ie, the
      major sodium pump isoform of the kidneys, as would be expected of a putative
      natriuretic hormone.

PMID- 11230318
TI  - Brown Norway chromosome 13 confers protection from high salt to consomic Dahl S
      rat.
AB  - Consomic rats (SS.BN13), in which chromosome 13 from normotensive inbred Brown
      Norway rats from a colony maintained at the Medical College of Wisconsin (BN/Mcw)
      was introgressed into the background of Dahl salt-sensitive (SS/Mcw) rats, also
      maintained in a colony at the Medical College of Wisconsin, were bred. The
      present studies determined the mean arterial pressure (MAP) responses to salt and
      renal and peripheral vascular responses to norepinephrine and angiotensin II; 24
      hour protein excretion and histological analyses were used to assess renal
      pathology in rats that received a high salt (4% NaCl) diet for 4 weeks. MAP of
      rats measured daily during the fourth week averaged 170+/-3.3 mm Hg in SS/Mcw
      rats, 119+/-2.1 mm Hg in SS.BN13 rats, and 103+/-1.3 mm Hg in BN/Mcw rats. After
      salt depletion, MAP fell an average of 27+/-4.5 mm Hg in SS/Mcw rats, 9+/-2.6 mm
      Hg in SS.BN13 rats, and 11+/-3.0 mm Hg in BN/Mcw rats. Protein excretion of
      SS/Mcw rats on a high salt diet averaged 189+/-30 mg/24 h, 63+/-18 mg/24 h in
      SS.BN13 rats, and 40+/-6.4 mg/24 h in BN/Mcw rats. Compared with SS.BN13 and
      BN/Mcw rats, SS/Mcw rats exhibited significantly greater increases of renal
      vascular resistance in response to intravenous norepinephrine and angiotensin II.
      Severe medullary interstitial fibrosis and tubular necrosis after a high salt
      diet were found consistently in SS/Mcw rat kidneys but were largely absent in the
      SS.BN13 and BN/Mcw rat kidneys. A similar degree of glomerular sclerosis was
      found in both SS/Mcw and SS.BN13 rats. In rats fed a 0.4% salt diet, the
      glomerular filtration rate of SS/Mcw rats was significantly less than that of
      BN/Mcw and SS.BN13 rats. These results reveal a powerful gene, or set of genes,
      within chromosome 13 of BN/Mcw rats that confers protection from the detrimental
      effects of high salt to the SS/Mcw rats.

PMID- 11230320
TI  - NO Inhibits NaCl absorption by rat thick ascending limb through activation of
      cGMP-stimulated phosphodiesterase.
AB  - In the isolated, perfused rat thick ascending limb (THAL), L-arginine (L-Arg)
      stimulates endogenous nitric oxide (NO) production, which inhibits NaCl
      absorption. However, the intracellular cascade responsible for the effects of NO
      has not been studied. We hypothesized that endogenous NO inhibits THAL NaCl
      transport by increasing cGMP, which activates protein kinase G (PKG) and cGMP
      stimulated phosphodiesterase (PDE II), which, in turn, decreases cAMP levels.
      THALs from rats were isolated and perfused, and net chloride flux (J(Cl-)) was
      measured. L-Arg was used to stimulate NO production. Adding L-Arg (0.5 mmol/L) to
      the bath decreased J(Cl-) from 154.4+/-9.9 to 101.9+/-14.1 pmol. mm(-1). min(-1),
      a 35.2% decrease (n=6; P<0.05). In the presence of the soluble guanylate cyclase
      inhibitor LY-83583 (10 micromol/L), adding L-Arg to the bath did not affect THAL
      J(Cl-) (143.7+/-28.1 versus 136.7+/-22.2 pmol. mm(-1). min(-1); n=6). LY-83583
      alone had no effect on J(Cl-). In the presence of the PDE II inhibitor erythro-9
      (2-hydroxy-3-nonyl) adenine (EHNA) 50 micromol/L, L-Arg reduced J(Cl-) by only
      13% (142.1+/-8.9 versus 122.7+/-11.5 pmol. mm(-1). min(-1); P<0.05; n=6). EHNA
      alone had no effect on THAL J(Cl-). In the presence of 10(-5) mol/L dibutyryl
      (db)-cAMP, L-Arg did not significantly reduce J(Cl-) (116.3+/-18.2 versus 102.6+/
      15.6 pmol. mm(-1). min(-1); n=6). db-cAMP (10(-5) mol/L) had no effect on THAL
      J(Cl-). In the presence of the PKG inhibitor KT-5823 (2 micromol/L), L-Arg
      lowered J(Cl-) from 142.6+/-14.1 to 85.9+/-8.3 pmol. mm(-1). min(-1), a decrease
      of 35.6% (n=8; P<0.05). We conclude that (1) endogenous NO inhibits THAL J(Cl-)
      by stimulating soluble guanylate cyclase and increasing cGMP; (2) NO inhibits
      THAL J(Cl-) by stimulation of PDE II, which, in turn, decreases cAMP levels; and
      (3) PKG does not mediate NO-induced inhibition of THAL J(Cl-).

PMID- 11230321
TI  - Structure-activity relationships for the hypertensinogenic activity of ouabain:
      role of the sugar and lactone ring.
AB  - Elevated levels of an endogenous ouabain circulate in many patients with
      essential hypertension. However, in contrast to ouabain, digoxin does not induce
      hypertension. This study investigated the hypothesis that within a single cardiac
      glycoside, the structural elements that induce hypertension differ from those
      responsible for high potency as a sodium pump inhibitor. Normal male Sprague
      Dawley rats received infusions of vehicle (VEH), rhamnose (RHA), ouabain (OUA),
      ouabagenin (OGN), dihydro-ouabain (DHO), iso-ouabain (ISO), and a lactone ring
      opened analog (ORO) at 30 microgram. kg(-1). 24 h(-1) for 5 weeks via
      subcutaneous osmotic pumps. Cuff pressures were taken weekly. At the end of the
      study, trunk blood was harvested, extracted by C18 column, and subjected to high
      performance liquid chromatography. Fractions were analyzed for OUA, OGN, and DHO
      by immunoassay. In OUA-, OGN-, and DHO-infused rats, 1 main peak of
      immunoreactivity corresponding to the infused agent was found. No evidence of in
      vivo conversion to OUA or DHO was found for any analog except ORO. At 5 weeks,
      systolic blood pressures in VEH, RHA, OUA, OGN, DHO, ISO, and ORO were 132+/-2.5,
      133+/-1.5, 159+/-2.6,* 154+/-4,* 167+/-4,* 171+/-2.2,* and 169+/-2.4* mm Hg,
      respectively (*P<0.01 versus VEH and RHA, P<0.05 versus OUA). The
      hypertensinogenic activity was greater than OUA in 3 analogs (DHO, ISO, and ORO)
      in which the lactone was saturated, conformationally restrained by linkage with
      the oxygen at C14, or opened, respectively. These compounds were weak inhibitors
      of dog kidney Na,K-ATPase. Thus, RHA and the unsaturated lactone ring are crucial
      to the high potency of OUA as an inhibitor of the sodium pump but appear to be
      unrelated to its ability to induce hypertension. The conclusion that this form of
      hypertension is mediated primarily by the steroid nucleus suggests also that OUA
      may have a mechanism of action independent of the sodium pump.

PMID- 11230322
TI  - Src and Rac mediate endothelin-1 and lysophosphatidic acid stimulation of the
      human brain natriuretic peptide promoter.
AB  - Brain natriuretic peptide (BNP) gene expression accompanies cardiac hypertrophy
      and heart failure. The vasoconstrictor endothelin-1 (ET) may be involved in the
      development of these diseases. ET has also been shown to activate phospholipase
      A(2) (PLA(2)), and the resulting metabolites are important second messengers. We
      studied how ET and PLA(2) metabolites regulate BNP gene expression. The human BNP
      (hBNP) promoter (from -1818 to +100) coupled to a luciferase reporter gene was
      transferred into neonatal ventricular myocytes (NVMs), and luciferase activity
      was measured as an index of promoter activity. ET induced BNP mRNA in NVMs as
      assessed by Northern blot. It also stimulated the hBNP promoter, an effect
      completely inhibited by actinomycin D. To test the involvement of different
      PLA(2) isoforms, transfected cells were treated with various PLA(2) inhibitors
      before stimulation with ET. Only Ca(2+)-independent PLA(2) blockade prevented ET
      stimulated hBNP promoter activity. The PLA(2) metabolite lysophosphatidic acid
      (LPA) also activated the hBNP promoter, but arachidonic acid itself did not. ET
      regulation of the hBNP promoter is pertussis toxin-sensitive. The nonreceptor
      tyrosine kinase Src and the small GTPase Rac mediate the effects of both ET and
      LPA in stimulation of the hBNP promoter. We studied the involvement of cis
      elements in ET-stimulated hBNP promoter activity. Deletion of BNP promoter
      sequences from -1818 to -408 and from -408 to -40 reduced the effect of ET by 60%
      and 80%, respectively. Moreover, ET-stimulated luciferase activity was reduced by
      50% when the proximal GATA element was mutated. These data suggest that (1) ET
      activates the hBNP promoter through a transcriptional mechanism; (2) LPA, perhaps
      generated by iPLA(2), is involved in the effect of ET; (3) Src and Rac mediate ET
      and LPA stimulation of the hBNP promoter; and (4) ET regulation of the hBNP
      promoter targets both distal and proximal cis elements.

PMID- 11230324
TI  - Regression of renal vascular fibrosis by endothelin receptor antagonism.
AB  - In previous studies, we have observed that endothelin participates in the
      progression of renal vascular and glomerular fibrosis during hypertension by
      activating collagen I gene synthesis. The present study investigated whether
      administration of endothelin receptor antagonists leads to the regression of
      renal sclerotic lesions. Experiments were performed in transgenic mice harboring
      the luciferase gene under the control of the collagen I-alpha2 chain promoter.
      Hypertension was induced by long-term inhibition of nitric oxide synthesis by
      N(G)-nitro-L-arginine methyl ester (L-NAME); systolic pressure gradually
      increased, reaching a plateau of 165 mm Hg after 10 weeks of hypertensive
      treatment. At the same time, collagen I gene expression was increased 2- and 5
      fold compared with control animals in afferent arterioles and glomeruli,
      respectively (P<0.01). This increase was accompanied by the appearance of
      sclerotic lesions within the renal vasculature. When renal vascular lesions had
      been established (20 weeks of L-NAME), animals were divided into 2 subgroups: the
      one continued to receive L-NAME, whereas in the other, bosentan, a dual
      endothelin antagonist, was coadministered with L-NAME for an additional period of
      10 weeks. Bosentan coadministration did not alter the increased systolic pressure
      at 30 weeks; in contrast, collagen I gene activity returned almost to control
      levels in renal vessels and glomeruli. In this subgroup of animals, renal
      vascular lesions (collagen and/or extracellular matrix deposition) and mortality
      rates were substantially reduced compared with untreated mice. These data
      indicate that endothelin participates in the mechanism(s) of renal vascular
      fibrosis by activating collagen I gene. Treatment with an endothelin antagonist
      normalizes expression of collagen I gene and leads to the regression of renal
      vascular fibrosis and to the improvement of survival, thus providing a
      complementary curative approach against renal fibrotic complications associated
      with hypertension.

PMID- 11230323
TI  - Endothelin type a receptor blockade attenuates the hypertension in response to
      chronic reductions in uterine perfusion pressure.
AB  - A chronic reduction in uterine perfusion pressure in pregnant rats is associated
      with a significant elevation in mean arterial pressure (MAP) and reduction in
      kidney function. The purpose of this study was to examine the role of endothelin
      in mediating the hypertension in response to chronic reductions in uterine
      perfusion pressure in conscious, chronically instrumented, pregnant rats. MAP in
      pregnant rats with chronic reductions in uterine perfusion pressure (123.0+/-1.8
      mm Hg) was significantly higher than that in control pregnant rats (101.3+/-4.0
      mm Hg). Renal expression of preproendothelin mRNA as determined by ribonuclease
      protection assay was also significantly elevated in the medulla (>45%, P<0.05)
      and in the cortex (>22%, P:<0.05) of the pregnant rats with chronic reductions in
      uterine perfusion pressure compared with control pregnant rats. Chronic
      administration of the selective endothelin type A receptor antagonist (ABT-627, 5
      mg/kg per day for 10 days) markedly attenuated the increase in MAP observed in
      the pregnant rats with chronic reductions in uterine perfusion pressure (103.3+/
      5.6 mm Hg, plus endothelin antagonist; P<0.05). However, endothelin type A
      receptor blockade had no significant effect on blood pressure in the normal
      pregnant animals (96.0+/-2.7 mm Hg, plus endothelin antagonist). These findings
      suggest that endothelin plays a major role in mediating the hypertension produced
      by chronic reductions in uterine perfusion pressure in pregnant rats.

PMID- 11230325
TI  - Endothelin-1 enhances eicosanoids-induced coronary smooth muscle contraction by
      activating specific protein kinase C isoforms.
AB  - Endothelin-1 (ET-1), a potent vasoconstrictor, has been implicated in the
      pathogenesis of coronary vasospasm by enhancing coronary vasoconstriction to
      vasoactive eicosanoids; however, the cellular mechanisms involved are unclear. We
      investigated whether physiological concentrations of ET-1 enhance coronary smooth
      muscle contraction to vasoactive eicosanoids by activating specific protein
      kinase C (PKC) isoforms. Cell contraction was measured in single smooth muscle
      cells isolated from porcine coronary arteries, intracellular free Ca(2+)
      ([Ca(2+)](i)) was measured in fura-2-loaded cells, and the cytosolic and
      particulate fractions were examined for PKC activity and reactivity with isoform
      specific anti-PKC antibodies using Western blots. In Hanks' solution (1 mmol/L
      Ca(2+)), ET-1 (10 pmol/L) did not increase basal [Ca(2+)](i) (81+/-2 nmol/L), but
      it did cause cell contraction (9%) that was inhibited by GF109203X (10(-6)
      mol/L), an inhibitor of Ca(2+)-dependent and Ca(2+)-indpendent PKC isoforms. The
      vasoactive eicosanoid prostaglandin F(2alpha) (PGF(2alpha), 10(-7) mol/L) caused
      increases in cell contraction (11%) and [Ca(2+)](i) (108+/-7 nmol/L) that were
      inhibited by the Ca(2+) channel blocker diltiazem (10(-6) mol/L). Pretreatment
      with ET-1 (10 pmol/L) for 10 minutes enhanced cell contraction to PGF(2alpha)
      (35%) with no additional increase in [Ca(2+)](i) (112+/-8 nmol/L). Direct
      activation of PKC by phorbol 12,13-dibutyrate (PDBu, 10(-7) mol/L) caused cell
      contraction (10%) and enhanced PGF(2alpha) contraction (33%) with no additional
      increase in [Ca(2+)](i) (115+/-7 nmol/L). The ET-1-induced enhancement of
      PGF(2alpha) contraction was inhibited by Go6976 (10(-6) mol/L), an inhibitor of
      Ca(2+)-dependent PKC isoforms. Both ET-1 and PDBu caused an increase in PKC
      activity in the particulate fraction and a decrease in the cytosolic fraction and
      increased the particulate/cytosolic PKC activity ratio. Western blots revealed
      the Ca(2+)-dependent alpha-PKC and the Ca(2+)-independent delta-, epsilon-, and
      zeta-PKC isoforms. In resting tissues, alpha- and epsilon-PKC were mainly
      cytosolic, delta-PKC was mainly in the particulate fraction, and zeta-PKC was
      equally distributed in the cytosolic and particulate fraction. ET-1 (10 pmol/L)
      alone or PDBu (10(-7) mol/L) alone caused translocation of epsilon-PKC from the
      cytosolic to the particulate fraction, localized delta-PKC more in the
      particulate fraction, but did not change the distribution of zeta-PKC.
      PGF(2alpha) (10(-7) mol/L) alone did not change PKC activity. In tissues
      pretreated with ET-1 or PDBu, PGF(2alpha) caused additional increases in alpha
      PKC activity. Thus, the enhancement of PGF(2alpha)-induced coronary smooth muscle
      contraction by physiological concentrations of ET-1 involves activation and
      translocation of alpha-PKC in addition to delta- and epsilon-PKC isoforms, and
      this may represent one possible cellular mechanism by which ET-1 could enhance
      coronary vasoconstriction to vasoactive eicosanoids in coronary vasospasm.

PMID- 11230326
TI  - Role of endothelin and isoprostanes in slow pressor responses to angiotensin II.
AB  - We tested the hypothesis that angiotensin II (Ang II)-induced stimulations of
      endothelin (ET) and isoprostanes are implicated in the slow pressor responses to
      Ang II. We infused either vehicle (group 1) or Ang II (groups 2 to 4)
      intravenously at 5 ng/kg per minute via osmotic pumps for 15 days into Sprague
      Dawley rats. Groups 3 and 4 received 30 mg/kg per day of either losartan (Ang II
      type 1 receptor blocker) or bosentan (ET(A) and ET(B) receptor blocker) in their
      drinking water. We measured systolic blood pressure (SBP) every 3 days during the
      infusion. Plasma levels of Ang II, ET, isoprostanes, and urinary nitrites were
      determined at 15 days. Vehicle infusion did not change SBP (from 138+/-13 to
      136+/-2 mm Hg at day 15). Circulating Ang II, ET, and isoprostane levels were
      35+/-9, 39+/-3, and 111+/-10 pg/mL, respectively, whereas urinary nitrites were
      2.3+/-0.4 microgram/d. Ang II increased SBP (from 133+/-10 to 158+/-8 mm Hg),
      plasma Ang II (179+/-77 pg/mL), and isoprostanes (156+/-19 pg/mL) without
      altering ET levels (38+/-5 pg/mL) or urinary nitrites (1.8+/-0.5 microgram/d).
      Losartan prevented Ang II-induced increases in SBP and isoprostanes (SBP went
      from 137+/-5 to 120+/-4 mm Hg; isoprostanes were 115+/-15 pg/mL) while increasing
      urinary nitrite levels (5.2+/-1.1 microgram/d). Losartan did not alter Ang II
      (141+/-57 pg/mL) or ET (40+/-4 pg/mL) levels. Bosentan also blocked Ang II
      induced hypertension (from 135+/-4 to 139+/-3 mm Hg) but did not decrease
      isoprostanes (146+/-14 pg/mL). Ang II (63+/-11 pg/mL), ET levels (46+/-2 pg/mL),
      and urinary nitrites (2.8+/-0.4 microgram/d) were not altered. In conclusion, our
      results suggest that low-dose Ang II increases isoprostanes via its Ang II type 1
      receptor and causes an ET-dependent hypertension, without altering circulating ET
      levels.

PMID- 11230327
TI  - Role of endothelin in intermittent hypoxia-induced hypertension.
AB  - Clinical studies suggest that sleep apnea causes systemic hypertension. In
      addition, patients with sleep apnea have elevated plasma levels of endothelin-1
      (ET-1). We hypothesized that the intermittent hypoxia/hypercapnia (IH) associated
      with sleep apnea causes hypertension by increasing ET-1 production. To test this
      hypothesis, rats with arterial and venous catheters were placed in Plexiglas
      chambers. IH rat chambers were flushed with an N(2)-CO(2) mixture for 90 seconds
      to achieve hypoxia/hypercapnia (5% O(2)-5% CO(2)) followed by 90 seconds of
      compressed air to achieve normoxia (21% O(2)-0% CO(2)). Control rat chambers were
      flushed with 90 seconds of air-air cycles. Cycles for both groups were repeated 8
      hours per day for 11 days. Resting mean arterial pressure (MAP) and heart rate
      were recorded daily before the start of exposure. After 11 days, MAP was
      significantly elevated in IH rats compared with initial MAP (109+/-5 mm Hg
      initial, 139+/-11 mm Hg day 11) and compared with air-air rats (110+/-4 mm Hg).
      On day 11, cumulative doses of PD145065 (a nonselective ET-receptor antagonist)
      were administered intravenously to the rats breathing room air. PD145065 caused a
      dose-dependent decrease in MAP in IH rats but did not alter MAP in air-air rats.
      Plasma ET-1 measured by radioimmunoassay was significantly increased on days 5
      and 11 in the IH rats compared with day 1 and compared with air-air rats. There
      was no significant change in plasma ET-1 over time in air-air rats. We conclude
      that IH exposure increases both MAP and plasma ET-1 and that the increased ET-1
      may contribute to the hypertension.

PMID- 11230328
TI  - Role of endothelin B receptors in enhancing endothelium-dependent nitric oxide
      mediated vascular relaxation during high salt diet.
AB  - High salt diet is often associated with increases in blood pressure, and the
      state of activation of endothelium-dependent vascular relaxation pathways is
      critical under these conditions. Basal activation of endothelial endothelin B
      (ET(B)) receptors by endothelin has been suggested to stimulate the release of
      factors that promote vascular relaxation. However, whether ET(B) receptors play a
      role in enhancing endothelium-dependent vascular relaxation during high salt diet
      is unclear. In this study, we investigated whether chronic treatment with an
      ET(B) receptor antagonist is associated with impaired endothelium-dependent
      vascular relaxation and enhanced vascular reactivity particularly during high
      salt diet. Isometric contraction was measured in aortic strips isolated from male
      Sprague-Dawley rats on normal sodium (NS, 1%) and high sodium diet (HS, 8%) for 7
      days and untreated or treated with the ET(B) receptor antagonist A-192621 (30
      mg/kg per day) for 5 days. The mean arterial pressure was (in mm Hg) 122+/-3 in
      NS, 132+/-3 in HS, 144+/-2 in NS/ET(B) antagonist, and 171+/-12 in HS/ET(B)
      antagonist rats. In endothelium-intact strips, phenylephrine (Phe, 10(-5) mol/L)
      increased active stress to 7.6+/-1.0x10(3)N/m(2) in NS rats and 8.2+/
      0.9x10(3)N/m(2) in HS rats. Phe (10(-5) mol/L) -induced stress was significantly
      greater in NS/ET(B) antagonist (11.3+/-0.9x10(3)N/m(2)) than NS and far greater
      in HS/ET(B) antagonist (14.1+/-0.1.2x10(3)N/m(2)) than HS rats. Also, Phe was
      more potent in NS/ET(B) antagonist and HS/ET(B) antagonist rats (ED(50)=0.3x10(
      7) and 0.15x10(-7) mol/L) than in NS and HS rats (ED(50)=0.8x10(-7) and 0.7x10(
      7) mol/L). Removal of the endothelium enhanced Phe-induced contraction
      significantly in NS and to a greater extent in HS, but not in NS/ET(B) antagonist
      or HS/ET(B) antagonist rats. In endothelium-intact strips, acetylcholine (ACh)
      caused relaxation of Phe contraction that was less in NS/ET(B) antagonist than NS
      and far less in HS/ET(B) antagonist than HS rats. Pretreatment of endothelium
      intact strips with L-NAME (10(-4) mol/L), to inhibit nitric oxide (NO) synthase,
      or with methylene blue (10(-5) mol/L) or 1H-[1,2,4]oxadiazolo[4,3]-quinoxalin-1
      one (ODQ, 10(-6) mol/L), to inhibit cGMP production in smooth muscle, inhibited
      ACh-induced relaxation and enhanced Phe-induced contraction significantly in NS
      and HS, slightly in NS/ET(B) antagonist, but not in HS/ET(B) antagonist rats.
      Measurement of basal and ACh-induced nitrite/nitrate production from aortic
      strips showed a significant reduction in NS/ET(B) antagonist compared with NS,
      and a greater reduction in HS/ET(B) antagonist compared with HS rats. Relaxation
      of Phe contraction with sodium nitroprusside was not significantly different
      among the different groups of rats. Thus, an endothelial ET(B) receptor-mediated
      pathway of vascular relaxation involving release of NO seems to be active under
      basal conditions and may protect against excessive vasoconstriction and increased
      blood pressure particularly during high salt diet.

PMID- 11230329
TI  - Evidence that reduced renal medullary nitric oxide synthase activity of dahl s
      rats enables small elevations of arginine vasopressin to produce sustained
      hypertension.
AB  - On the basis of observations supporting the functional importance of nitric oxide
      (NO) in the regulation of renal medullary function, and a reduced nitric oxide
      synthase (NOS) enzyme activity in the outer medulla of the Dahl salt-sensitive
      (SS/Mcw) rats, we hypothesized that these inbred rats would have reduced capacity
      to synthesize renal medullary NO. This reduced capacity would sensitize them to
      the hypertensive effects of small elevations of circulating arginine vasopressin
      (AVP). SS/Mcw and Brown Norway (BN/Mcw) rats with implanted arterial and venous
      catheters were fed a 0.4% salt diet and infused intravenously for 14 days with a
      subpressor dose of AVP (2 ng/kg per min). Mean arterial pressure (MAP) was
      measured 2 hours daily in unanesthetized rats maintained in their home cages. MAP
      in SS/Mcw rats increased during day 1 of AVP infusion from a control level of
      127+/-0.9 mm Hg to an average of 147+/-1.6 mm Hg after 14 days. MAP did not
      return to control values during the 3 days after the end of AVP infusion. BN/Mcw
      rats showed no changes of MAP during 14 days of AVP infusion (90.4+/-0.6 mm Hg
      and 92.3+/-0.4 mm Hg). Northern blot analysis of renal tissue from vehicle
      (saline) -infused rats demonstrated that NOS I and NOS III mRNA expression was
      significantly less in SS/Mcw rats in the renal outer medulla compared with BN/Mcw
      rats. We conclude that small, normally subpressor elevations of plasma AVP can
      produce chronic hypertension in SS/Mcw rats and that this phenomenon is related
      to the reduced medullary NOS enzyme activity, which in turn reduces the AVP
      stimulated NO synthesis.

PMID- 11230330
TI  - Superoxide excess in hypertension and aging: a common cause of endothelial
      dysfunction.
AB  - There is evidence in humans that hypertension and aging similarly impair
      endothelial function, although the mechanism remains unclear. Superoxide anion
      (O(2)(-)) is a major determinant of nitric oxide (NO) bioavailability and thus
      endothelial function. We sought to determine the relationship between endothelial
      function, O(2)(-), and age in normotensive Wistar-Kyoto (WKY) and stroke-prone
      spontaneously hypertensive rats (SHRSP). Aortic rings were removed from female
      WKY and SHRSP at 3 to 4 months (young) and 9 to 12 months (old). O(2)(-)
      generation by aortic rings was measured before and after removal of the
      endothelium or incubation with N(G) nitro-L-arginine methyl ester,
      diphenyleneiodonium, or apocynin. Levels of p22phox were studied with
      immunohistochemistry and used as a marker of NAD(P)H oxidase expression. NO
      bioavailability was significantly lower in old WKY compared with young WKY
      (P=0.0009) and in old SHRSP compared with young SHRSP (P=0.005). O(2)(-)
      generation was significantly greater in old WKY compared with young WKY
      (P=0.0001). Removal of the endothelium and N(G) nitro-L-arginine methyl ester
      treatment resulted in a significant reduction in O(2)(-) generation in old SHRSP
      (P=0.009 and 0.001, respectively). Diphenyleneiodonium significantly reduced
      O(2)(-) generation in 12-month WKY (P=0.008) and 12-month SHRSP (P=0.009).
      Apocynin attenuated O(2)(-) generation by older WKY (P=0.038) and SHRSP
      (P=0.028). p22phox was increased in older animals compared with young. We
      conclude that NO bioavailability decreases with age in female WKY and SHRSP.
      O(2)(-) generation increases with age in WKY and is higher in SHRSP and may
      contribute to the reduced NO by scavenging. NAD(P)H oxidase may contribute to the
      age-related increase in O(2)(-).

PMID- 11230332
TI  - Increased oxidative stress in experimental renovascular hypertension.
AB  - The pathophysiological mechanisms responsible for maintenance of chronic
      renovascular hypertension remain undefined. Excess angiotensin II generation may
      lead to release of reactive oxygen species and increased vasoconstrictor
      activity. To examine the potential involvement of oxidation-sensitive mechanisms
      in the pathophysiology of renovascular hypertension, blood samples were collected
      and renal blood flow measured with electron-beam computed tomography in pigs 5
      and 10 weeks after induction of unilateral renal artery stenosis (n=7) or sham
      operation (n=7). Five weeks after procedure, plasma renin activity and mean
      arterial pressure were elevated in hypertensive pigs. Levels of prostaglandin
      F2alpha (PGF(2alpha))-isoprostanes, vasoconstrictors and markers of oxidative
      stress, also were significantly increased (157+/-21 versus 99+/-16 pg/mL; P<0.05)
      and correlated with both plasma renin activity (r=0.83) and arterial pressure
      (r=0.82). By 10 weeks, plasma renin activity returned to baseline but arterial
      pressure remained elevated (144+/-10 versus 115+/-5 mm Hg; P:<0.05). Isoprostane
      levels remained high and still correlated directly with the increase in arterial
      pressure (r=0.7) but not with plasma renin activity. Stenotic kidney blood flow
      was decreased at both studies. In shock-frozen cortical tissue, ex vivo
      endogenous intracellular radical scavengers were significantly decreased in both
      kidneys. The present study demonstrates, for the first time, that in early
      renovascular hypertension, an increase in plasma renin activity and arterial
      pressure is associated with increased systemic oxidative stress. When plasma
      renin activity later declines, PGF(2alpha)-isoprostanes remain elevated, possibly
      due to local activation or slow responses to angiotensin II, and may participate
      in sustenance of arterial pressure. Moreover, oxidation-sensitive mechanisms may
      influence ischemic and hypertensive parenchymal renal injury.

PMID- 11230331
TI  - Reactive oxygen species-mediated homologous downregulation of angiotensin II type
      1 receptor mRNA by angiotensin II.
AB  - Recent studies suggest a crucial role of reactive oxygen species (ROS) for the
      signaling of angiotensin (Ang) II through Ang II type 1 receptor (AT(1)-R).
      However, the role of ROS in the regulation of AT(1)-R expression has not been
      explored. In this study, we examined the effect of an antioxidant on the
      homologous downregulation of AT(1)-R by Ang II. Ang II (10(-6) mol/L) decreased
      AT(1)-R mRNA with a peak suppression at 6 hours of stimulation in rat aortic
      vascular smooth muscle cells. Preincubation of vascular smooth muscle cells with
      N:-acetylcysteine (NAC), a potent antioxidant, almost completely inhibited the
      Ang II-induced downregulation of AT(1)-R mRNA. The effect of NAC was due to
      stabilization of the AT(1)-R mRNA that was destabilized by Ang II. The Ang II
      induced AT(1)-R mRNA downregulation was also blocked by PD98059, an extracellular
      signal-regulated protein kinase (ERK) kinase inhibitor. Ang II-induced ERK
      activation was inhibited by NAC as well as by PD98059. Exogenous H(2)O(2) also
      suppressed AT(1)-R mRNA. These results suggest that the production of ROS and the
      activation of ERK are critical for the downregulation of AT(1)-R mRNA. The
      generation of ROS through stimulation of AT(1)-R not only mediates signaling of
      Ang II but also may play a crucial role in the adaptation process of AT(1)-R to
      the sustained stimulation of Ang II.

PMID- 11230333
TI  - Production and actions of superoxide in the renal medulla.
AB  - The present study characterized the biochemical pathways responsible for
      superoxide (O(2)(-.)) production in different regions of the rat kidney and
      determined the role of O(2)(-.)in the control of renal medullary blood flow (MBF)
      and renal function. By use of dihydroethidium/DNA fluorescence spectrometry with
      microtiter plates, the production of O(2)(-. )was monitored when tissue
      homogenate from different kidney regions was incubated with substrates for the
      major O(2)(-.)-producing enzymes, such as NADH/NADPH oxidase, xanthine oxidase,
      and mitochondrial respiratory chain enzymes. The production of O(2)(-. )via NADH
      oxidase was greater (P<0.05) in the renal cortex and outer medulla (OM) than in
      the papilla. The mitochondrial enzyme activity for O(2)(-.)production was higher
      (P<0.05) in the OM than in the cortex and papilla. Compared with NADH oxidase and
      mitochondrial enzymes, xanthine oxidase and NADPH oxidase produced much less
      O(2)(-. )in the kidney under this condition. Overall, the renal OM exhibited the
      greatest enzyme activities for O(2)(-.)production. In anesthetized rats, renal
      medullary interstitial infusion of a superoxide dismutase inhibitor,
      diethyldithiocarbamate, markedly decreased renal MBF and sodium excretion.
      Diethyldithiocarbamate (5 mg/kg per minute by renal medullary interstitial
      infusion [RI]) reduced the renal medullary laser-Doppler flow signal from 0.6+/
      0.04 to 0.4+/-0.03 V, a reduction of 33%, and both urine flow and sodium
      excretion decreased by 49%. In contrast, a membrane-permeable superoxide
      dismutase mimetic, 4-hydroxytetramethyl-piperidine-1-oxyl (TEMPOL, 30 micromol/kg
      per minute RI) increased MBF and sodium excretion by 34% and 69%, respectively.
      These effects of TEMPOL on renal MBF and sodium excretion were not altered by
      pretreatment with N(G)-nitro-L-arginine methyl ester (10 microgram/kg per minute
      RI). We conclude that (1) renal medullary O(2)(-. )is primarily produced in the
      renal OM; (2) both NADH oxidase and mitochondrial enzymes are responsible for the
      O(2)(-.)production in this kidney region; and (3) O(2)(-. )exerts a tonic
      regulatory action on renal MBF.

PMID- 11230334
TI  - Oxidative stress in a rat model of obesity-induced hypertension.
AB  - The mechanisms underlying the development of hypertension in obesity are not yet
      fully understood. We recently reported the development of hypertension in a rat
      model of diet-induced obesity. When Sprague-Dawley rats (n=60) are fed a
      moderately high fat diet (32 kcal% fat) for 10 to 16 weeks, approximately half of
      them develop obesity (obesity-prone [OP] group) and mild hypertension (158+/-3.4
      mm Hg systolic pressure), whereas the other half (obesity-resistant [OR] group)
      maintains a body weight equivalent to that of a low fat control group and is
      normotensive (135.8+/-3.8 mm Hg). We examined the potential role of oxidative
      stress in the development of hypertension in this model. Lipid peroxides measured
      as thiobarbituric acid-reactive substances showed a significant increase in the
      LDL fraction of OP rats (2.8+/-0.32 nmol malondialdehyde/mg protein) compared
      with OR and control rats (0.9+/-0.3 nmol malondialdehyde/mg protein). Also,
      aortic and kidney thiobarbituric acid-reactive substances showed a significant (3
      and 5- fold) increase in OP rats after 16 weeks of diet. In addition, superoxide
      generation by aortic rings, measured by lucigenin luminescence, showed a 2-fold
      increase in the OP group compared with both the OR and control groups. In
      addition, free isoprostane excretion and nitrotyrosine in the kidney showed an
      increase in OP rats only. The urine and plasma nitrate/nitrite measured by the
      LDH method showed a 1.8-fold decrease in OP rats compared with OR rats. However,
      endothelial NO synthase expression in the kidney cortex and medulla assessed by
      reverse transcriptase-polymerase chain reaction showed a strong increase in the
      OP rats versus OR and control rats (endothelial NO synthase/beta-actin ratio
      1.3+/-0.04 in OP rats versus 0.44+/-0.02 in OR rats), suggesting a possible shift
      toward superoxide production by the enzyme. Collectively, the data show a
      decreased NO bioavailability in OP animals that is due in part to the increased
      oxidative stress.

PMID- 11230335
TI  - Oxidized-LDL enhances coronary vasoconstriction by increasing the activity of
      protein kinase C isoforms alpha and epsilon.
AB  - Oxidized low-density lipoprotein (ox-LDL) plays a critical role in the
      development of atherosclerotic coronary vasospasm; however, the cellular
      mechanisms involved are not fully understood. We tested the hypothesis that ox
      LDL enhances coronary vasoconstriction by increasing the activity of specific
      protein kinase C (PKC) isoforms in coronary smooth muscle. Active stress was
      measured in de-endothelialized porcine coronary artery strips; cell contraction
      and [Ca(2+)](i) were monitored in single coronary smooth muscle cells loaded with
      fura-2; and the cytosolic and particulate fractions were examined for PKC
      activity and reactivity with isoform-specific anti-PKC antibodies with Western
      blots. Ox-LDL (100 microgram/mL) caused slow but significant increases in active
      stress to 1.3+/-0.4x10(3) N/m(2) and cell contraction (10%) that were completely
      inhibited by GF109203X (10(-6) mol/L), an inhibitor of Ca(2+)-dependent and 
      independent PKC isoforms, with no significant change in [Ca(2+)](i). 5
      Hydroxytryptamine (5-HT; 10(-7) mol/L) and KCl (24 mmol/L) caused increases in
      cell contraction and [Ca(2+)](i) that were inhibited by the Ca(2+) channel
      blocker verapamil (10(-6) mol/L). Ox-LDL enhanced coronary contraction to 5-HT
      and KCl with no additional increases in [Ca(2+)](i). Direct activation of PKC by
      phorbol 12-myristate13-acetate (PMA; 10(-7) mol/L) caused a contraction similar
      in magnitude and time course to ox-LDL-induced contraction and enhanced 5-HT- and
      KCl-induced contraction with no additional increases in [Ca(2+)](i). The ox-LDL
      induced enhancement of 5-HT and KCl contraction was inhibited by Go6976 (10(-6)
      mol/L), an inhibitor of Ca(2+)-dependent PKC isoforms. Both ox-LDL and PMA caused
      an increase in PKC activity in the particulate fraction, a decrease in the
      cytosolic fraction, and an increase in the particulate/cytosolic PKC activity
      ratio. Western blots revealed the Ca(2+)-dependent PKC-alpha and the Ca(2+)
      independent PKC-delta, -epsilon, and -zeta isoforms. In unstimulated tissues, PKC
      alpha- and -epsilon were mainly cytosolic, PKC-delta was mainly in the
      particulate fraction, and PKC-zeta was equally distributed in the cytosolic and
      particulate fractions. Ox-LDL alone or PMA alone caused translocation of PKC
      epsilon from the cytosolic to particulate fraction, whereas the distribution
      pattern of PKC-alpha, -delta, and -zeta remained unchanged. 5-HT (10(-7) mol/L)
      alone and KCl alone did not change PKC activity. In tissues pretreated with ox
      LDL or PMA, 5-HT and KCl caused additional increases in PKC-alpha activity.
      Native LDL did not significantly affect coronary contraction, [Ca(2+)](i), or PKC
      activity. These results suggest that ox-LDL causes coronary contraction via
      activation of the Ca(2+)-independent PKC-epsilon and enhances the contraction to
      [Ca(2+)](i)-increasing agonists by activating the Ca(2+)-dependent PKC-alpha.
      Activation of PKC-alpha and -epsilon may represent a possible cellular mechanism
      by which ox-LDL could enhance coronary vasospasm.

PMID- 11230336
TI  - Tyrosine kinase involvement in renal arteriolar constrictor responses to
      angiotensin II.
AB  - Experiments were performed to test the hypothesis that tyrosine kinase activity
      contributes to renal arteriolar contractile responses to angiotensin (Ang) II.
      Rats were subjected to short-term enalaprilat treatment to decrease endogenous
      Ang II formation before tissue was harvested for experiments with the in vitro
      blood-perfused juxtamedullary nephron technique. Acute surgical papillectomy was
      used to avoid the indirect afferent arteriolar effect of Ang II that arises
      through increased tubuloglomerular feedback sensitivity. Arteriolar lumen
      diameter responses to 1 and 10 nmol/L Ang II were monitored by videomicroscopic
      methods before and during treatment with various tyrphostin compounds: 100
      micromol/L AG18 (broad-spectrum tyrosine kinase inhibitor), 100 nmol/L AG1478
      (selective epidermal growth factor receptor tyrosine kinase inhibitor), or 100
      micromol/L AG9 (inactive analog). Baseline afferent arteriolar lumen diameter
      averaged 23.5+/-1.2 micrometer and was not influenced by any tyrphostin. Ang II
      (10 nmol/L) decreased afferent diameter by 11.1+/-1.0 micrometer under untreated
      conditions, a response that was not altered by AG9 but significantly blunted by
      AG18 (34+/-9% inhibition) or AG1478 (52+/-8% inhibition). AG18 did not suppress
      afferent arteriolar contractile responses to membrane depolarization (20 to 55
      mmol/L K(+ )bath). Efferent arteriolar baseline diameter averaged 24.1+/-0.8
      micrometer and was unaltered by AG18 or AG1478; however, efferent diameter
      responses to 10 nmol/L Ang II were diminished 52+/-10% by AG18 and 51+/-13% by
      AG1478. These observations indicate that Ang II signaling in renal afferent and
      efferent arteriolar vascular smooth muscle is either mediated or modulated by
      tyrosine kinase activity, including that of the epidermal growth factor receptor
      tyrosine kinase.

PMID- 11230337
TI  - p38 Map kinase regulates vascular smooth muscle cell collagen synthesis by
      angiotensin II in SHR but not in WKY.
AB  - Vascular remodeling in hypertension is associated with cell growth and increased
      deposition of extracellular matrix components, particularly collagen. Mechanisms
      underlying these processes are unclear, but MAP kinases, particularly ERK1/2 and
      p38 MAP kinase, may be important. We studied the role of ERK1/2 and p38 MAP
      kinase in vascular smooth muscle cell (VSMC) collagen synthesis and growth
      mediated by angiotensin (Ang) II in spontaneously hypertensive rats (SHR).
      Cultured mesenteric VSMC from Wistar-Kyoto rats and SHR were used.
      Phosphorylation of ERK1/2 and p38 MAP kinase were assessed by Western blots with
      phosphospecific antibodies. Ang II-stimulated DNA and collagen synthesis were
      determined by measuring incorporation of (3)H-thymidine and (3)H-proline,
      respectively. mRNA expression of procollagen I and III was determined by reverse
      transcription-polymerase chain reaction. Ang II increased ERK1/2 and p38 MAP
      kinase phosphorylation. Responses were augmented in SHR. Effects were inhibited
      by irbesartan, a selective AT(1) antagonist, but not by PD123319, a selective
      AT(2) blocker. Ang II stimulated (3)H-thymidine and (3)H-proline incorporation.
      These actions were enhanced 2- to 3-fold in SHR. PD98059, selective inhibitor of
      the ERK1/2 pathway, attenuated Ang II-induced growth and collagen effects and
      normalized responses in SHR. SB212190, a selective p38 MAP kinase inhibitor, did
      not alter Ang II-elicited DNA synthesis but reduced collagen production and mRNA
      expression of procollagen I and III in SHR. These data demonstrate that (1) Ang
      II-mediated activation of p38 and ERK1/2 is increased in SHR, (2) augmented
      growth responses are generated by ERK1/2-dependent, p38 MAP kinase-independent
      pathways, and (3) p38 MAP kinase influences Ang II-induced collagen production in
      SHR but not in Wistar-Kyoto rats. These results indicate differential roles of
      ERK1/2 and p38 MAP kinase in AT(1)-stimulated VSMC growth and collagen
      production, which may contribute to vascular remodeling in hypertension.

PMID- 11230338
TI  - Mitogenic and antiapoptotic actions of hepatocyte growth factor through ERK,
      STAT3, and AKT in endothelial cells.
AB  - Hepatocyte growth factor (HGF), a member of the angiogenic growth factors, may
      play a pivotal role in the regulation of endothelial cells, inasmuch as HGF shows
      mitogenic and antiapoptotic actions in endothelial cells. Because the mechanism
      of these actions is still unclear, we examined the signal transduction system of
      HGF in human aortic endothelial cells. Treatment of endothelial cells with
      recombinant HGF (rHGF) resulted in a significant increase in DNA synthesis as
      assessed by thymidine incorporation. Importantly, phosphorylation of
      extracellular signal-related kinase (ERK) and Akt by rHGF was clearly observed.
      Thus, we further examined the effects of specific inhibitors of ERK or Akt on
      cell proliferation. Pretreatment with PD98059, a mitogen-activated protein kinase
      kinase inhibitor, significantly attenuated cell proliferation induced by rHGF,
      whereas inhibitors of phosphatidylinositol-3-OH kinase, wortmannin, and LY
      294002, did not. Interestingly, treatment with rHGF significantly increased the
      phosphorylation of the signal transducers and activators of transcription (STAT)3
      (Ser727), whereas PD98059 attenuated the phosphorylation of Ser727 induced by
      rHGF. In addition, treatment with rHGF significantly increased the promoter
      activity of c-fos, which includes the sis-inducible element and serum response
      element, whereas PD98059 completely attenuated the activation of the c-fos
      promoter induced by rHGF. In contrast, inhibition of Akt by wortmannin and LY
      294002 failed to inhibit the phosphorylation of STAT3 and c-fos activation. On
      the other hand, treatment with rHGF attenuated the increase in LDH release and
      caspase-3 activity induced by tumor necrosis factor-alpha stimulation. In
      contrast to DNA synthesis, wortmannin and LY-294002 markedly attenuated the
      decrease in caspase-3 activity mediated by rHGF, whereas PD98059 did not.
      Overall, the present study demonstrated that HGF stimulated cell proliferation
      through the ERK-STAT3 (Ser727) pathway and had an antiapoptotic action through
      the phosphatidylinositol-3-OH kinase-Akt pathway in human aortic endothelial
      cells. These findings provide new perspectives in the role of HGF in
      cardiovascular disease.

PMID- 11230339
TI  - Angiotensin II induces migration and Pyk2/paxillin phosphorylation of human
      monocytes.
AB  - Angiotensin (Ang) II has been shown to enhance the development of atherosclerotic
      lesions. Migration of monocytes is an early critical step in the atherosclerotic
      process. To elucidate mechanisms by which Ang II promotes atherogenesis, we
      investigated its effects on human monocyte migration. Ang II induced migration of
      human peripheral blood monocytes (HPBM) and human THP-1 monocytes at
      concentrations between 0.01 and 1 micromol/L, with a 3.6+/-0.6-fold induction in
      HPBM and a 4.8+/-0.9-fold induction in THP-1 cells at 1 micromol/L Ang II (both
      P<0.01 versus unstimulated cells). Addition of the Ang II receptor type 1 (AT1-R)
      antagonist losartan (1 to 100 micromol/L) suppressed Ang II-induced migration of
      HPBM and THP-1 monocytes in a dose-dependent manner, demonstrating an AT1-R
      mediated mechanism. Ang II-directed migration was also blocked by the Src kinase
      inhibitor PP2 (10 micromol/L), by the extracellular-regulated protein kinase (ERK
      1/2) inhibitor PD98059 (30 micromol/L), and by the p38-MAPK inhibitor SB203580
      (10 micromol/L), indicating that Src, ERK 1/2, and p38 are all involved in Ang II
      induced migration of HPBM and human THP-1 monocytes. The proline-rich tyrosine
      kinase 2 (Pyk2) and paxillin are 2 cytoskeleton-associated proteins involved in
      cell movement, phosphorylated by Ang II in other cell types, and abundantly
      expressed in monocytes. Ang II (1 micromol/L) induced Pyk2 and paxillin
      phosphorylation in human THP-1 monocytes, peaking after 10 minutes for Pyk2 with
      a 6.7+/-0.9-fold induction and after 2 minutes for paxillin with a 3.2+/-0.4-fold
      induction. Ang II-induced phosphorylation of both proteins was suppressed by
      losartan and the Src inhibitor PP2, whereas no effect was observed with PD98059
      and SB203580. This study demonstrates a novel proatherogenic action of Ang II on
      human monocytes by stimulating their migration, through an AT1-R-dependent
      process, involving signaling through Src, ERK 1/2, and p38. Furthermore, the
      promigratory actions of Ang II in human monocytes are associated with the
      phosphorylation of 2 cytoskeleton-associated proteins, Pyk2 and paxillin.

PMID- 11230340
TI  - Workshop: mechanisms and cardiovascular damage in hypertension.
AB  - Angiotensin (Ang) II is considered a regulatory hormone stimulating vascular
      smooth muscle cell constriction, aldosterone release from the adrenal gland, and
      sodium reabsorption in the renal tubule. Furthermore, Ang II may be formed and
      act locally as a chemokine, inducing tyrosine phosphorylation, cell growth,
      hypertrophy, and differentiation. In addition, evidence has recently accrued
      showing that Ang II is important in stimulating the production of reactive oxygen
      species and the activation of ancient inflammatory mechanisms. The transcription
      factor nuclear factor kappa-B is pivotal to these processes. Nuclear factor kappa
      B activation stimulates the expression of a gene menagerie important to
      chemoattraction, surface adhesion molecule expression, coagulation, and
      inflammation. Anti-inflammatory interventions may have therapeutic utility.

PMID- 11230341
TI  - Differential inhibition of functional dilation of small arterioles by
      indomethacin and glibenclamide.
AB  - Indomethacin or glibenclamide treatments attenuate functional dilation of larger
      diameter "feed" arterioles paired with venules in hamster cremaster muscle. We
      tested the hypothesis that release of cyclooxygenase products from venules is
      important for functional dilation of third- and fourth-order arterioles. We also
      tested whether ATP-sensitive potassium channels are important during functional
      dilation of smaller arterioles. The microcirculation of hamster cremaster muscle
      was visualized with in vivo video microscopy. We measured diameter responses of
      third- and fourth-order arterioles paired and unpaired with venules in response
      to 2 minutes of muscle field stimulation (40 microseconds, 10 V, 1 Hz). Control
      diameters of vessels were 31+/-2 (n=19), 13+/-1 (n=12), 12+/-2 (n=12), and 10+/-1
      (n=12) for paired and unpaired third-order and paired and unpaired fourth-order
      arterioles, respectively. In all groups, field stimulation resulted in increases
      in mean control diameter of >80%. Indomethacin (28 micromol/L) superfused on the
      preparation was used to inhibit cyclooxygenase metabolism, or glibenclamide (10
      micromol/L) was used to block ATP-sensitive potassium channels. Indomethacin
      attenuated arteriolar vasodilations to electrical stimulation in paired third
      order vessels only, whereas glibenclamide attenuated this vasodilation in all 4
      groups. These results support a role for ATP-sensitive potassium channels in
      functional dilation of arterioles of all sizes regardless of whether or not they
      are paired with venules. Conversely, a role for cyclooxygenase products is
      limited to larger "feed arterioles" paired with venules. This study provides
      further evidence that venules may be the source of prostaglandin release during
      functional hyperemia.

PMID- 11230342
TI  - Expression of cell cycle proteins in blood vessels of angiotensin II-infused
      rats: role of AT(1) receptors.
AB  - Angiotensin II is an important modulator of cell growth through AT(1) receptors,
      as demonstrated both in vivo and in vitro. We investigated the role of proteins
      involved in the cell cycle, including cyclin D1, cyclin-dependent kinase 4
      (cdk4), and cyclin-dependent kinase inhibitors p21 and p27 in blood vessels of
      angiotensin II-infused rats and the effect therein of the AT(1)-receptor
      antagonist losartan. Male Sprague-Dawley rats were infused for 7 days with
      angiotensin II (120 ng/kg per minute SC) and/or treated with losartan (10 mg/kg
      per day orally). DNA synthesis in mesenteric arteries was evaluated by
      radiolabeled (3)H-thymidine incorporation. The expression of cyclin D1, cdk4,
      p21, and p27, which play critical roles during the G(1)-phase of the cell cycle
      process, was examined by Western blot analysis. Tail-cuff systolic blood pressure
      (mm Hg) was elevated (P<0.01, n=9) in angiotensin II-infused rats (161.3+/-8.2)
      versus control rats (110.1+/-5.3) and normalized by losartan (104.4+/-3.2).
      Radiolabeled (3)H-thymidine incorporation (cpm/100 microgram DNA) showed that
      angiotensin II infusion significantly increased DNA synthesis (152+/-5% versus
      102+/-6% of control rats, P<0.05). Expression of cyclin D1 and cdk4 was
      significantly increased in the angiotensin II group to 213.7+/-8% and 263.6+/-37%
      of control animals, respectively, whereas expression of p21 and p27 was
      significantly decreased in the angiotensin II group to 23.2+/-10.4% and 10.3+/
      5.3% of control animals, respectively. These effects induced by angiotensin II
      were normalized in the presence of losartan. Thus, when AT(1) receptors are
      stimulated in vivo, DNA synthesis is enhanced in blood vessels by activation of
      cyclin D1 and cdk4. Reduction in cell cycle kinase inhibitors p21 and p27 may
      contribute to activation of growth induced by in vivo AT(1) receptor stimulation.

PMID- 11230343
TI  - Impaired beta-adrenergic hyperpolarization in arteries from prehypertensive
      spontaneously hypertensive rats.
AB  - Stimulation of beta-adrenoceptors leads to vascular smooth muscle
      hyperpolarization, presumably through the beta-adrenoceptors/Gs protein/adenylate
      cyclase/ATP-sensitive K(+)-channels (KATP) signaling cascade, which may play an
      important role in the sympathetic control of membrane potential. beta
      Adrenoceptor-mediated hyperpolarization has been shown to be impaired in the
      established stage of experimental hypertension. The present study tested the
      hypothesis that beta-adrenergic hyperpolarization may be defective before the
      development of hypertension in some forms of genetic hypertension. We evaluated
      beta-adrenoceptor-mediated hyperpolarization using microelectrodes in mesenteric
      resistance arteries from 5-week-old, prehypertensive, spontaneously hypertensive
      rats (SHR) and age-matched Wistar-Kyoto rats (WKY). Isoproterenol-induced
      hyperpolarization was significantly smaller in SHR than in WKY (10(-7) mol/L: 
      4.6+/-0.6 versus -7.8+/-0.8 mV, P<0.01; 10(-6) mol/L -7.8+/-0.5 versus -9.8+/-0.6
      mV, P<0.05; n=9). Furthermore, hyperpolarization to cholera toxin, a direct
      activator of Gs protein, was also impaired in SHR. On the other hand,
      hyperpolarization to forskolin, an adenylate cyclase activator, and to
      levcromakalim, a KATP opener, was comparable between groups. These findings
      suggest that beta-adrenoceptor-mediated hyperpolarization is defective in SHR
      before the development of hypertension, presumably because of an abnormality at
      the Gs protein site. Considering the importance of membrane potential in the
      control of vascular tone, altered beta-adrenergic control of membrane potential
      might play a role in the development of hypertension in SHR.

PMID- 11230344
TI  - gamma-Aminobutyric acid (GABA)--A function and binding in the paraventricular
      nucleus of the hypothalamus in chronic renal-wrap hypertension.
AB  - The goal of this study was to determine whether gamma-aminobutyric acid
      (GABA)ergic transmission and GABA binding are altered in chronic renal-wrap
      hypertension. Three groups of hypertensive and sham-operated rats were prepared
      for separate protocols. Four weeks later, the animals were prepared with femoral
      artery catheters for the measurement of mean arterial pressure. In all groups,
      blood pressure was significantly higher in the renal-wrapped animals. In the
      first study, bilateral microinjection of the GABA-A antagonist, bicuculline (50
      pmol/site), into the paraventricular nucleus of the hypothalamus (PVN) caused a
      greater increase in arterial pressure (21.9+/-1.4 versus 16.7+/-1.8 mm Hg,
      P<0.05) and heart rate (135+/-15 versus 98+/-12 bpm, P=0.064) in hypertensive
      rats. [(3)H]Flunitrazepam was used to measure binding to the GABA-A receptor.
      Magnocellular neurons and the adjacent medial parvicellular neurons had more
      intense binding compared with the remainder of the PVN. B(max) was greater for
      the higher density binding area; the K(d) value was less in the high-density
      region. There were no differences in these parameters between normotensive and
      hypertensive animals. Competitive reverse transcription-polymerase chain reaction
      was used to measure the expression of mRNA for the alpha(1) subunit of the GABA-A
      receptor. No difference was observed in the mRNA between renal-wrapped and sham
      operated rats. In summary, inhibition of GABA-A receptors in the PVN is augmented
      in the chronic phase of hypertension and is unrelated to a change in the
      expression of the number or affinity to the receptor. These findings suggest that
      the greater GABAergic activity is the result of an increase in GABA release in
      the PVN in chronic renal-wrap hypertension.

PMID- 11230345
TI  - gamma-Aminobutyric acid(B) receptor-mediated responses in the nucleus tractus
      solitarius are altered in acute and chronic hypertension.
AB  - The increase in mean arterial pressure evoked by injection of the gamma
      aminobutyric acid (GABA)(B) agonist baclofen into the nucleus tractus solitarius
      (NTS) is greater in spontaneously hypertensive rats and renal wrap chronically
      hypertensive (CHT) rats compared with normotensive (NT) controls. We report here
      that the baclofen-induced pressor response (BIPR) is enhanced after acute
      hypertension (AHT) of only 30 minutes. Sprague-Dawley rats were anesthetized with
      Inactin, paralyzed, and artificially ventilated. As we previously reported, after
      unilateral electrolytic ablation of the NTS, microinjection of 40 pmol baclofen
      into the contralateral NTS of NT rats resulted in a BIPR of 22+/-1 mm Hg (n=12).
      During the infusion of phenylephrine for 30 minutes (AHT), the BIPR was 39+/-5 mm
      Hg (n=10), significantly greater than the response in NT rats (P<0.01) and no
      different from the response in CHT rats (39+/-5 mm Hg, n=7). Baclofen has both
      presynaptic and postsynaptic effects. To eliminate the presynaptic component of
      the baclofen response, sinoaortic denervation (SAD) was performed before the
      microinjections. The magnitude of the BIPR was 12+/-1 mm Hg in NT-SAD rats (n=8),
      12+/-1 mm Hg in AHT-SAD rats (n=12), and 20+/-3 mm Hg in CHT-SAD rats (n=7). The
      BIPR is enhanced in both CHT and AHT rats. It appears that the increase in
      baroreceptor afferent input to NTS during phenylephrine-induced AHT provides a
      greater substrate for presynaptic inhibition by baclofen because the postsynaptic
      component of the baclofen response is the same in NT-SAD and AHT-SAD. The
      enhanced BIPR in CHT rats appears to be associated with an enhancement of both
      the presynaptic and postsynaptic components of the response.

PMID- 11230347
TI  - Superoxide inhibits neuronal nitric oxide synthase influences on afferent
      arterioles in spontaneously hypertensive rats.
AB  - This study was designed to determine the influence of increased superoxide anion
      in neuronal nitric oxide synthase (nNOS)-dependent regulation of afferent
      arterioles in spontaneously hypertensive rats (SHR). Afferent arteriolar
      diameters of male Wistar-Kyoto rats (WKY) and SHR were assessed in vitro with the
      blood-perfused juxtamedullary nephron technique and averaged 21.6+/-1.6 (n=6) and
      18.8+/-1.2 (n=7) micrometer, respectively. The superoxide dismutase mimetic
      Tempol (1, 10, and 100 micromol/L) did not influence afferent arterioles of WKY
      but significantly increased afferent arteriolar diameters of SHR by 20.6+/-5.5%,
      25.2+/-5.4%, and 23.3+/-4.9%, respectively. In WKY (n=6), the nNOS inhibitor S
      methyl-L-thiocitrulline (L-SMTC; 10 micromol/L) and the NOS inhibitor N(omega)
      nitro-L-arginine (L-NNA; 100 micromol/L) significantly decreased afferent
      arteriolar diameters (19.6+/-1.6 micrometer) by 11.9+/-3.1% and 21.0+/-3.9%,
      respectively. In SHR (n=7), L-SMTC did not influence afferent arteriolar
      diameters (21.0+/-1.5 micrometer), but L-NNA exerted an afferent arteriolar
      constriction (14.8+/-3.2%) that was similar to the response observed in WKY.
      Experiments were also performed in the presence of 100 micromol/L Tempol. In
      afferent arterioles of WKY (n=6), Tempol treatment did not modulate the basal
      diameters (21.5+/-1.2 micrometer) or the constrictor response to L-SMTC (10.6+/
      2.1%) or L-NNA (19.3+/-3.3%). In SHR (n=8), Tempol significantly increased
      afferent arteriolar diameters by 22.5+/-4.3% and enhanced afferent arteriolar
      constrictor responses to L-SMTC (18.4+/-2.7%) and L-NNA (31.9+/-2.6%). However,
      the nitric oxide donor S-nitroso-N-acetylpenicillamine (10 micromol/L), which
      similarly increased afferent arteriolar diameters (17.2+/-2.3%, n=6), did not
      affect afferent arteriolar responses to L-SMTC (1.5+/-2.7%) or L-NNA (18.6+/
      2.3%). These suggest that superoxide anion inhibits the control of afferent
      arteriolar diameters by nNOS in SHR.

PMID- 11230346
TI  - 20-Hydroxyeicosatetraenoic acid mediates angiotensin ii-induced phospholipase d
      activation in vascular smooth muscle cells.
AB  - Angiotensin II (Ang II) activates cytosolic phospholipase A(2) (cPLA(2)) and
      phospholipase D (PLD) in rabbit vascular smooth muscle cells (VSMCs). Ang II also
      activates ras/mitogen-activated protein (MAP) kinase in VSMCs; this activation is
      mediated by 20-hydroxyeicosatetraenoic acid (HETE) and 12(S)-HETE, which are
      metabolites of arachidonic acid generated by cytochrome P450 4A and lipoxygenase,
      respectively, produced on activation of cPLA(2). The purpose of this study was to
      determine if Ang II-induced PLD activation in VSMCs is mediated through the
      ras/extracellular signal-regulating kinase (ERK) pathway by arachidonic acid
      metabolites that are generated consequent to cPLA(2) stimulation. Inhibitors of
      PLD (C(2) ceramide), phosphatidate phosphohydrolase (propranolol), and
      diacylglycerol lipase (RHC 80267) attenuated Ang II-induced arachidonic acid
      release. Ang II-induced PLD activation, as measured by [(3)H]phosphatidylethanol
      production, was inhibited by C(2) ceramide but not by propranolol or RHC 80267.
      Ang II-induced PLD activation was decreased by the inhibitor methyl
      arachidonylfluorophosphate (MAFP) and the antisense oligonucleotide of cPLA(2).
      Inhibitors of lipoxygenases (baicalein) and cytochrome P450 4A (ODYA) attenuated
      Ang II-induced PLD activation. 20-HETE and 12(S)-HETE increased PLD activity.
      Inhibitors of ras farnesyltransferase (FPT III and BMS-191563) and MAP kinase
      kinase (UO126) attenuated the increase in PLD activity elicited by 20-HETE and
      Ang II. PLD2 was the main isoform activated by Ang II in VSMCs. These data
      suggest that the CYP4A metabolite 20-HETE, which is generated from arachidonic
      acid after cPLA(2) activation by Ang II, stimulates the ras/MAP kinase pathway,
      which in turn activates PLD2 and releases further arachidonic acid for
      prostaglandin synthesis through the phosphatidate phosphohydrolase/diacylglycerol
      lipase pathway.

PMID- 11230349
TI  - Estradiol metabolites inhibit endothelin synthesis by an estrogen receptor
      independent mechanism.
AB  - Estradiol inhibits endothelin-1 synthesis, an effect that may contribute to the
      cardiovascular protective effects of estradiol. Recent findings that estradiol
      inhibits neointima formation in mice lacking estrogen receptors suggests that the
      cardiovascular protective effects of estradiol may be mediated by means of an
      estrogen receptor-independent mechanism. Because 2-hydroxyestradiol and 2
      methoxyestradiol, metabolites of estradiol with little/no affinity for estrogen
      receptors, are more potent than estradiol in inhibiting vascular smooth muscle
      cell growth, we investigated whether these metabolites also inhibit endothelin-1
      synthesis by means of an receptor-independent mechanism. Treatment of porcine
      coronary artery endothelial cells for 4 to 24 hours with 0.001 to 1 micromol/L of
      estradiol, 2-hydroxyestradiol, or 2-methoxyestradiol concentration-dependently
      inhibited basal as well as serum-induced (2.5%), TNFalpha-induced (10 ng/mL),
      angiotensin II-induced (100 nmol/L), and thrombin-induced (4 U/mL) endothelin-1
      synthesis. Estradiol, 2-hydroxyestradiol, and 2-methoxyestradiol also inhibited
      serum-induced mitogen-activated protein kinase activity. As compared with
      estradiol, its metabolites were more potent in inhibiting endothelin-1 secretion
      and mitogen activated protein kinase activity. The inhibitory effects of 2
      hydroxyestradiol and 2-methoxyestradiol on endothelin-1 release and mitogen
      activated protein kinase activity were not blocked by ICI182780 (50 micromol/L),
      an estrogen receptor antagonist. Our findings indicate that the estradiol
      metabolites 2-hydroxyestradiol and 2-methoxyestradiol potently inhibit endothelin
      1 synthesis by means of an estrogen receptor-independent mechanism. This effect
      of estradiol metabolites may be mediated by inhibition of mitogen activated
      protein kinase activity and may contribute to the cardioprotective effects of
      estradiol.

PMID- 11230348
TI  - Angiotensin II signaling to phospholipase D in renal microvascular smooth muscle
      cells in SHR.
AB  - Angiotensin II (Ang II)-induced phospholipase D (PLD) activity is greater in
      aortic smooth muscle from spontaneously hypertensive rats (SHR) versus
      normotensive Wistar-Kyoto rats (WKY). Whether and how this signaling pathway is
      altered in preglomerular microvascular smooth muscle cells (PGSMCs), a cell type
      that may participate in genetic hypertension, is unknown. The goals of the
      present study were to determine in SHR and WKY PGSMCs the following: (1) whether
      Ang II induces PLD activity; (2) whether the effect of Ang II on PLD activity is
      greater in SHR; (3) which PLD isoform is stimulated by Ang II; (4) what signaling
      pathway mediates Ang II-induced PLD stimulation; and (5) whether the signaling
      pathways mediating Ang II-induced PLD activity are different in SHR and WKY. The
      EC(50) for Ang II-induced PLD stimulation in SHR was 10-fold lower than the
      EC(50) in WKY, and both were inhibited by L-158,805, an AT(1) antagonist.
      Inhibitors of phosphoinositol-3-kinase and protein kinase C did not block Ang II
      induced PLD activity in SHR and WKY PGSMCs. Catalytically-inactive constructs of
      PLD2 and RhoA, but not PLD1, ADP ribosylation factor 1 (ARF1), ARF6, or ADP
      ribosylation factor nucleotide exchange factor (ARNO) blocked Ang II-induced PLD
      activity in SHR and WKY PGSMCs. Brefeldin A completely blocked Ang II-induced PLD
      activity in SHR but only slightly reduced Ang II-induced PLD activity in WKY
      PGSMCs. Therefore, we conclude that in PGSMCs, the effect of Ang II on PLD
      activity is (1) greater in SHR; (2) mediated by AT(1) receptors signaling to
      PLD2; (3) transduced primarily by Rho proteins; and (4) inhibited in SHR by
      brefeldin A.

PMID- 11230350
TI  - Effects of estradiol and its metabolites on glomerular endothelial nitric oxide
      synthesis and mesangial cell growth.
AB  - Reduced nitric oxide synthesis by glomerular endothelial cells and increased
      proliferation of glomerular mesangial cells is associated with glomerular
      remodeling that leads to accelerated glomerulosclerosis. Estradiol induces nitric
      oxide synthesis and slows the progression of renal disease. Because the estradiol
      metabolites 2-hydroxyestradiol and 2-methoxyestradiol are more potent than
      estradiol in inhibiting growth of vascular smooth muscle cells, which are
      phenotypically similar to mesangial cells, we compared the effects of estradiol,
      2-hydroxyestradiol, and 2-methoxyestradiol on growth of glomerular mesangial
      cells and on basal nitric oxide synthesis by glomerular endothelial cells. In
      human glomerular mesangial cells, estradiol and its metabolites concentration
      dependently (1 nmol/L to 10 micromol/L) inhibited serum (2.5%)-induced DNA
      synthesis, cell proliferation, and collagen synthesis with the order of potency
      being 2-methoxyestradiol > 2-hydroxyestradiol > estradiol. ICI182780 (100
      micromol/L, an estrogen receptor antagonist) blocked the growth inhibitory
      effects of estradiol but not 2-hydroxyestradiol or 2-methoxyestradiol. Treatment
      with estradiol, but not 2-hydroxyestradiol and 2-methoxyestradiol, induced nitric
      oxide synthesis (P<0.05, assayed by the formation of (3)H-L-citrulline from (3)H
      L-arginine) in human glomerular endothelial cells, and these effects were blocked
      by ICI182780 and L-NMA (a nitric oxide synthesis inhibitor). In conclusion,
      estradiol may attenuate glomerulosclerosis by inducing nitric oxide synthesis via
      an estrogen receptor-dependent mechanism and by conversion to 2-hydroxyestradiol
      and 2-methoxyestradiol, which inhibit glomerular mesangial cell proliferation
      independent of estrogen receptors.

PMID- 11230351
TI  - Effect of estrogen replacement therapy on endothelial function in peripheral
      resistance arteries in normotensive and hypertensive postmenopausal women.
AB  - Both menopause and hypertension are associated with endothelial dysfunction and
      are risk factors for coronary heart disease. We evaluated forearm resistance
      artery endothelial function in hypertensive postmenopausal women (HPW, n=57) and
      compared it with endothelial function in normotensive postmenopausal women (NPW,
      n=67). In addition, we evaluated the effects of long-term estrogen replacement
      therapy (ERT, conjugated equine estrogen at a dose of 0.625 mg daily for 12
      weeks) on endothelial function in HPW (n=10) and NPW (n=35). Forearm blood flow
      (FBF) was measured by strain-gauge plethysmography during reactive hyperemia to
      assess endothelium-dependent vasodilation and after sublingual nitroglycerin
      (NTG) administration to assess endothelium-independent vasodilation. Basal FBF
      was similar in the NPW and HPW groups. The FBF in the HPW group during reactive
      hyperemia was significantly lower than that in the NPW group. Increases in FBF
      after NTG were similar in the 2 groups. ERT decreased the LDL cholesterol
      concentration and circulating ACE activity and increased estradiol and HDL
      cholesterol in both groups. Basal blood pressures, heart rate, FBF, and body
      weight did not change with ERT. After 12 weeks of ERT, the maximal FBF response
      during reactive hyperemia increased significantly in both groups. The improvement
      in reactive hyperemia after ERT was significantly greater in the HPW group than
      in the NPW group (49+/-8 versus 17+/-5%, P<0.05). Changes in FBF after sublingual
      NTG administration were similar before and after 12 weeks of ERT. These findings
      suggest that continued ERT improves forearm resistance artery endothelial
      function in postmenopausal women and that this beneficial effect is greater in
      patients that are hypertensive.

PMID- 11230352
TI  - Increased 2-methoxyestradiol production in human coronary versus aortic vascular
      cells.
AB  - Estradiol may be cardioprotective; however, the mechanisms involved remain
      unclear. Recent findings that estradiol attenuates neointima formation in
      estrogen receptor knockout mice suggest that the cardioprotective effects of
      estradiol may be mediated through estrogen receptor-independent mechanisms.
      Because 2-methoxyestradiol, an endogenous metabolite of estradiol with no
      affinity for estrogen receptors, is more potent than estradiol in inhibiting
      vascular smooth muscle cell growth, it is feasible that 2-methoxyestradiol
      mediates in part the cardioprotective effects of estradiol. To address this
      hypothesis, we examined the kinetics of 2-methoxyestradiol synthesis in vascular
      smooth muscle cells and endothelial cells. In human aortic smooth muscle cells,
      the V(max), K(m), and V(max)/K(m) ratio values for conversion of 2
      hydroxyestradiol to 2-methoxyestradiol were 19+/-0.69 pmol. min(-1) per 10(6)
      cells, 0.52+/-0.085 micromol/L, and 44+/-4.9 pmol. min(-1). micromol/L per 10(6)
      cells, respectively. In human coronary artery vascular smooth muscle cells, the
      V(max), K(m), and V(max)/K(m) ratio values for conversion of 2-hydroxyestradiol
      to 2-methoxyestradiol were 16+/-0.59 pmol. min(-1) per 10(6) cells, 0.23+/-0.011
      micromol/L, and 69+/-3.6 pmol. min(-1). micromol/L per 10(6) cells, respectively
      (all values significantly different compared with human aortic smooth muscle
      cells). Also, in human aortic versus coronary artery endothelial cells, the
      V(max) (33+/-0.24 versus 22+/-0.33 pmol. min(-1) per 10(6) cells, respectively),
      K(m) (0.20+/-0.010 versus 0.099+/-0.014 micromol/L, respectively), and
      V(max)/K:(m) (163+/-7.7 versus 243+/-41 pmol. min(-1). micromol/L per 10(6)
      cells, respectively) values were significantly different. Our results indicate
      that vascular smooth muscle and endothelial cells effectively metabolize 2
      hydroxyestradiol to 2-methoxyestradiol. The lower K(m) and higher V(max)/K(m)
      ratio of human coronary versus aortic cells indicate a faster rate of local
      metabolism of 2-hydroxyestradiol to 2-methoxyestradiol in the coronary
      circulation at low levels of 2-hydroxyestradiol.

PMID- 11230353
TI  - Central leptin infusion attenuates the cardiovascular and metabolic effects of
      fasting in rats.
AB  - The role of reduced leptin signaling in the regulation of cardiovascular
      responses to negative energy balance is not known. We tested the hypothesis that
      central infusion of leptin would attenuate the cardiovascular and metabolic
      responses to fasting. Male Sprague-Dawley rats, instrumented with telemetry
      devices and intracerebroventricular cannulas, were housed in metabolic chambers
      for continuous (24 hours) measurement of dark-phase (active) and light-phase
      (inactive) mean arterial pressure, heart rate, oxygen consumption, and
      respiratory quotient. Rats received central infusions of either saline (0.5
      microL/h) or leptin (42 ng/h) for 6 days through osmotic pumps and were either
      fed ad libitum or were fasted for 48 hours followed by refeeding for 4 days. In
      ad lib animals, continuous intracerebroventricular leptin infusion significantly
      reduced caloric intake, body weight, and respiratory quotient compared with
      saline controls while having no effect on mean arterial pressure or heart rate.
      Fasting reduced mean arterial pressure, heart rate, oxygen consumption, and
      respiratory quotient in rats receiving saline infusions. Fasting-induced
      reductions in mean arterial pressure were specific to the active phase and were
      not attenuated by central leptin infusion. In contrast, intracerebroventricular
      leptin, at a dose that had no cardiovascular effects in ad lib control animals,
      completely prevented fasting-induced decreases in light-phase heart rate and
      oxygen consumption and blunted fasting-induced reductions in dark-phase heart
      rate and oxygen consumption. The results are consistent with the hypothesis that
      reductions in central leptin signaling contribute to the integrated
      cardiovascular and metabolic responses to acute caloric deprivation.

PMID- 11230354
TI  - Inhibition of NO synthesis enhances chronic cardiovascular and renal actions of
      leptin.
AB  - Acute studies suggest that leptin has pressor and depressor actions, including
      stimulation of sympathetic activity as well as increased release of NO from the
      vascular endothelium. The goal of this study was to examine the role of NO in
      modulating the chronic blood pressure, heart rate, and renal responses to
      hyperleptinemia, comparable to that found in obesity-induced hypertension. Male
      Sprague-Dawley rats were implanted with arterial and venous catheters, and mean
      arterial pressure and heart rate were monitored continuously 24 h/d. After a 4
      day control period, the rats were infused with isotonic saline vehicle (n=6) or
      N(G)-nitro-L-arginine methyl ester (L-NAME, 10 microgram/kg per minute; n=9) to
      inhibit NO synthesis for 7 days. After 7 days of vehicle or L-NAME
      administration, leptin was infused intravenously for 7 days at a rate of 0.5
      microgram/kg per minute, followed by a leptin infusion at 1.0 microgram/kg per
      minute for 7 days, along with vehicle or L-NAME. A 21-day infusion of L-NAME
      alone (n=6) served as a control for the L-NAME+leptin rats. Although the low dose
      of leptin alone did not significantly elevate arterial pressure, it raised the
      heart rate by 18+/-3 bpm. The higher leptin infusion rate raised arterial
      pressure from 96+/-3 to 104+/-3 mm Hg but did not increase the heart rate
      further. L-NAME+leptin increased arterial pressure by 40+/-6 mm Hg and heart rate
      by 79+/-19 bpm compared with pretreatment levels. In control L-NAME rats, mean
      arterial pressure increased by 31+/-4 mm Hg, whereas the heart rate was not
      altered significantly compared with pretreatment levels. Neither chronic leptin
      infusion alone nor L-NAME alone altered the glomerular filtration rate or renal
      plasma flow significantly, but L-NAME+leptin reduced glomerular filtration rate
      by 27+/-11% and renal plasma flow by 47+/-9%. These results indicate that
      impaired NO synthesis mildly enhances the chronic renal hemodynamic and
      hypertensive effects of leptin but markedly amplifies the tachycardia caused by
      hyperleptinemia.

PMID- 11230355
TI  - Angiotensin II increases vesicular trafficking in brain neurons.
AB  - Our previous studies have established that angiotensin (Ang) II stimulates the
      release, uptake, and synthesis of norepinephrine (NE) in brain neurons involving
      distinct signal transduction pathways. However, little is known if this NE
      neuromodulatory effect is a result of Ang II activation of vesicular trafficking
      in the catecholaminergic neurons. Thus, the aim of this study was to determine if
      Ang II influences movement of vesicles in live neurons. Dopamine-beta-hydroxylase
      (DbetaH) fused to green fluorescence protein (GFP) has been used to trace
      vesicular movement in live neurons by confocal microscopy. Transfection by a
      plasmid containing GFP-DbetaH resulted in the expression of green fluorescence,
      representing approximately 100 kDa GFP-DbetaH fusion protein. The fluorescence
      was predominantly localized in the perinuclear region of the neuronal soma, with
      a few neurites also depicting the fluorescence. Ang II caused a dramatic
      redistribution of fluorescence. The fluorescence was translocated to the neurites
      in a time-dependent manner. As a result, the number of neurites depicting
      fluorescence was significantly increased. The translocation was blocked by
      losartan, an Ang II type 1 receptor subtype-specific antagonist and not by
      PD123319, an Ang II type 2 receptor subtype antagonist. High-magnification
      confocal microscopic examination revealed that Ang II treatment resulted in a
      distal movement of certain fluorescent clusters in the neurites at an average
      rate of 0.84+/-0.2 micrometer/s. These observations suggest increased vesicular
      trafficking is a key signaling event in Ang II stimulation of NE neuromodulation.

PMID- 11230356
TI  - Responses to central Na(+) and ouabain are attenuated in transgenic rats
      deficient in brain angiotensinogen.
AB  - Studies with angiotensin (Ang) II type 1 receptor blockers suggest that the brain
      renin-angiotensin system contributes to sodium-induced sympathoexcitation and
      hypertension. To provide more specific evidence for the involvement of Ang II,
      locally produced in the brain, transgenic rats were used, which express an
      antisense RNA against angiotensinogen mRNA specifically in the brain, reducing
      angiotensinogen levels in the brain by >90%. In freely moving transgenic rats and
      Sprague-Dawley rats as control animals, blood pressure and heart rate responses
      to intracerebroventricular infusion (3.8 microL/min for 10 minutes) of artificial
      cerebrospinal fluid and Na(+)-rich artificial cerebrospinal fluid (containing
      0.2, 0.3, and 0.45 mol/L Na(+)) as well as intracerebroventricular injection of
      ouabain (0.3 and 0.6 microgram/2 microL) were assessed. Central infusion of Na(+)
      rich artificial cerebrospinal fluid increased blood pressure and heart rate in a
      dose-related manner. However, the peak increases by each dose of Na(+) were
      attenuated by 50% to 70% in the transgenic versus Sprague-Dawley rats. Increases
      in blood pressure and heart rate in response to ouabain at both doses were
      attenuated by 55% to 70% in the transgenic versus Sprague-Dawley rats. In the
      hypothalamus, Ang I level was markedly lower (31+/-9 versus 76+/-13 pg/g, P<0.05)
      and Ang II level tended to be lower in the transgenic versus Sprague-Dawley rats.
      These results indicate that the production of angiotensins in the brain is
      decreased in transgenic rats. The attenuated sympathoexcitatory and pressor
      responses to ouabain and Na(+)-rich artificial cerebrospinal fluid in transgenic
      rats support the concept that the local brain renin-angiotensin system, that is,
      locally produced Ang II, plays an important role in the sympathoexcitatory
      effects of ouabain and sodium.

PMID- 11230357
TI  - Tonic excitatory input to the rostral ventrolateral medulla in Dahl salt
      sensitive rats.
AB  - The goal of the present study was to test the hypothesis that the balance of
      tonic excitation and inhibition of vasomotor neurons in the rostral ventrolateral
      medulla (RVLM) driven by excitatory amino acid (EAA)-mediated inputs to the RVLM
      is shifted toward excitation in Dahl salt-sensitive (DS) rats compared with Dahl
      salt-resistant (DR) rats. Glutamate and the EAA antagonist kynurenic acid were
      microinjected into the RVLM of chloralose-anesthetized DS and DR rats maintained
      on diets containing either 0.3% NaCl or 8.0% NaCl. DS rats had a higher arterial
      pressure than DR rats, and this difference was greatly exaggerated by high
      dietary salt intake. Bilateral injection of kynurenic acid (2.7 nmol) into the
      RVLM decreased mean arterial pressure by 16+/-2 mm Hg in DS rats fed a diet
      containing 0.3% NaCl, and this effect was significantly larger in DS rats fed the
      high-salt diet (40+/-2 mm Hg). In contrast, injections of kynurenic acid into the
      RVLM did not significantly decrease arterial pressure in DR rats fed either diet.
      In DR rats, the pressor response elicited by the injection of glutamate into the
      RVLM was potentiated in rats fed the high-salt diet. The glutamate-evoked pressor
      response was greater in DS rats compared with DR rats, and the response in DS
      rats was not influenced by the salt content of the diet. These data suggest that
      tonically active EAA inputs to the RVLM may contribute to salt-sensitive
      hypertension in the Dahl model.

PMID- 11230358
TI  - Differentiation of brain angiotensin type 1a and 1b receptor mRNAs: A specific
      effect of dehydration.
AB  - The objective was to examine the effect of dehydration on the expression of the
      angiotensin type 1 (AT(1)) receptor subtype mRNAs in mice by using an in situ
      hybridization method. The method used free-floating brain sections with (35)S
      labeled probes specific for the untranslated 5' (AT(1a)) and 3' (AT(1b)) regions.
      AT(1a) and AT(1b) mRNA levels in the subfornical organ (SFO) and anterior third
      ventricle (AV3V) were quantified by using a phosphor-imaging system. Emulsion
      autoradiography with cresyl violet counterstaining was used to show cellular
      expression. Adult male C57BL mice (25 to 30 g) were given water ad libitum or
      were deprived of water for 48 hours. Dehydration produced increases in plasma
      osmolality (349+/-6 versus 314+/-4 mOsm/kg) and hematocrit (58+/-2% versus 47+/
      1%). In situ hybridization showed that there was expression of AT(1a) and of
      AT(1b) mRNA in SFO and AV3V. Dehydration produced an increase in AT(1a) mRNA in
      both regions, with no changes noted for AT(1b). AT(1a) mRNA was increased in the
      AV3V region from 0.3+/-0.2 to 0.7+/-0.2 muCi/g and in the SFO from 0.6+/-0.3 to
      1.0+/-0.2 muCi/g. These results provide information regarding the localization
      and physiological importance of a subset of angiotensin receptors that are
      important in volume and blood pressure regulation. AT(1a) and AT(1b) mRNAs showed
      a similar pattern of expression in rostral forebrain osmosensitive regions.
      However, osmotic/volume stimulation with dehydration produced specific activation
      of AT(1a) receptors. This verifies the role of AT(1a) receptors in volume
      regulation but raises a question concerning the physiological role of the AT(1b)
      subtype.

PMID- 11230359
TI  - Norepinephrine reuptake is impaired in skeletal muscle of hypertensive rats in
      vivo.
AB  - Certain forms of experimental hypertension are characterized by organ-specific
      alterations of catecholaminergic pathways. The purpose of this study was to
      evaluate, in the same awake and freely moving normotensive Wistar-Kyoto rats
      (WKY) and spontaneously hypertensive rats (SHR) before and after the development
      of arterial hypertension, the norepinephrine (NE) turnover and, in particular,
      the neuronal NE reuptake activity that ends its effects once released from nerve
      terminals, in subcutaneous adipose tissue and in skeletal muscle, whose
      sympathetic efferents are respectively independent or dependent from
      baroreflexes. Plasma and tissue interstitial NE and 3,4-dihydroxyphenylethylene
      glycol (DHPG), its major deaminated metabolite, were measured before and after
      blockade of NE reuptake by tissue perfusion of desipramine through microdialysis
      probes. Arterial pressure and plasma NE in SHR were similar to those in WKY at 5
      weeks of age but increased at 16 weeks of age. In contrast, plasma DHPG was
      already higher in young SHR. Basal interstitial NE and DHPG were increased in
      both tissues of young and old SHR compared with age-matched WKY. Desipramine
      induced a higher rise of interstitial NE in SHR of both ages, with a lesser
      increase in the skeletal muscle of old compared with young SHR. These results
      indicate an increased NE turnover in prehypertensive and hypertensive SHR in both
      baroreflex-dependent and -independent tissues, not shown by plasma NE levels in
      young SHR. In the skeletal muscle, where sympathetic efferents are baroreflex
      dependent, the reduced interstitial NE reuptake contributes to the higher
      availability of interstitial NE for postsynaptic effects in old SHR.

PMID- 11230360
TI  - Potentiation of bradykinin by angiotensin-(1-7) on arterioles of spontaneously
      hypertensive rats studied in vivo.
AB  - In the present study, we investigated the potentiating effect of angiotensin-(1
      7) [Ang-(1-7)] on bradykinin (BK)-induced vasodilation in the mesenteric vascular
      bed of anesthetized spontaneously hypertensive rats using intravital microscopy.
      Topical application of BK and Ang-(1-7) induced vasodilation in mesenteric
      arterioles. The BK-induced effect, but not acetylcholine, sodium nitroprusside,
      or histamine responses, was potentiated in the presence of Ang-(1-7). This
      interaction was abolished by BK-B(2) and Ang-(1-7) antagonists (HOE 140 and A
      779, respectively), a K(+) channel blocker (tetraethylammonium), and
      cyclooxygenase inhibitors (indomethacin and diclofenac); however, nitric oxide
      synthase inhibition (Nomega-nitro-L-arginine methyl ester) did not modify the Ang
      (1-7)-potentiating activity. Long-term angiotensin-converting enzyme (ACE)
      inhibition increased BK and Ang-(1-7)-induced vasodilation. The BK potentiation
      by Ang-(1-7) was preserved after ACE inhibition, Ang II type 1 receptor blockade,
      or the combination of both treatments. The most striking finding of this study
      was the unexpected observation that the potentiation of BK vasodilation in
      spontaneously hypertensive rats treated short- or long-term with ACE inhibitors
      was reverted by the Ang-(1-7) antagonist A-779. Our results unmasked a key role
      for an Ang-(1-7)-related mechanism in mediating BK potentiation by ACE
      inhibitors.

PMID- 11230361
TI  - Cardiomyocytes bind and activate native human prorenin : role of soluble mannose
      6-phosphate receptors.
AB  - Cardiomyocytes bind, internalize, and activate recombinant human prorenin through
      mannose 6-phosphate/insulin-like growth factor II (M6P/IGFII) receptors. To
      investigate whether this also applies to native human prorenin, neonatal rat
      myocytes were incubated for 4 hours at 37 degrees C with various prorenin
      containing human body fluids. Uptake and activation by M6P/IGFII receptors were
      observed for plasma prorenin from subjects with renal artery stenosis and/or
      hypertension and for follicular fluid prorenin. The total amount of cellular
      renin and prorenin (expressed as percentage of the levels of renin and prorenin
      in the medium) after 4 hours of incubation was 4 to 10 times lower than after
      incubation with recombinant human prorenin. Although plasma contains alkaline
      phosphatases capable of inactivating the M6P label as well as soluble M6P/IGFII
      receptors that block prorenin binding in a competitive manner and proteins (eg,
      insulin, IGFII) that increase the number of cell-surface M6P/IGFII receptors,
      these factors were not responsible for the modest uptake of native human
      prorenin. Uptake did not occur during incubation of myocytes with plasma prorenin
      from anephric subjects or with amniotic fluid prorenin, and this was not due to
      the presence of excessively high levels of M6P/IGFII receptors and/or phosphatase
      activity in these fluids. In conclusion, myocytes are capable of binding,
      internalizing, and activating native human prorenin of renal and ovarian origin
      through M6P/IGFII receptors. Differences in prorenin glycosylation and/or
      phosphorylation as well as the concentration of soluble M6P/IGFII receptors and
      growth factors affecting cell-surface M6P/IGFII receptor density determine the
      amount of prorenin entering the heart and thus cardiac angiotensin II production.

PMID- 11230362
TI  - A(2b) receptors mediate the antimitogenic effects of adenosine in cardiac
      fibroblasts.
AB  - Adenosine inhibits growth of cardiac fibroblasts; however, the adenosine receptor
      subtype that mediates this antimitogenic effect remains undefined. Therefore, the
      goals of this study were to determine which adenosine receptor subtype mediates
      the antimitogenic effects of adenosine and to investigate the signal transduction
      mechanisms involved. In rat left ventricular cardiac fibroblasts, PDGF-BB (25
      ng/mL) stimulated DNA synthesis ((3)H-thymidine incorporation), cellular
      proliferation (cell number), collagen synthesis ((3)H-proline incorporation), and
      MAP kinase activity. The adenosine receptor agonists 2-chloroadenosine and 5'-N
      methylcarboxamidoadenosine, but not N(6)-cyclopentyladenosine, 4-aminobenzyl-5'-N
      methylcarboxamidoadenosine, or CGS21680, inhibited the growth effects of PDGF-BB,
      an agonist profile consistent with an A(2B) receptor-mediated effect. The
      adenosine receptor antagonists KF17837 and 1,3-dipropyl-8-p-sulfophenylxanthine,
      but not 8-cyclopentyl-1,3-dipropylxanthine, blocked the growth-inhibitory effects
      of 2-chloroadenosine and 5'-N-methylcarboxamidoadenosine, an antagonist profile
      consistent with an A(2) receptor-mediated effect. Antisense, but not sense or
      scrambled, oligonucleotides to the A(2B) receptor stimulated basal and PDGF
      induced DNA synthesis, cell proliferation, and collagen synthesis. Moreover, the
      growth-inhibitory effects of 2-chloroadenosine, 5'-N-methylcarboxamidoadenosine,
      and erythro-9-(2-hydroxy-3-nonyl) adenine plus iodotubericidin (inhibitors of
      adenosine deaminase and adenosine kinase, respectively) were abolished by
      antisense, but not scrambled or sense, oligonucleotides to the A(2B) receptor.
      Our findings strongly support the hypothesis that adenosine causes inhibition of
      CF growth by activating A(2B) receptors coupled to inhibition of MAP kinase
      activity. Thus, A(2B) receptors may play a critical role in regulating cardiac
      remodeling associated with CF proliferation. Pharmacologic or molecular
      biological activation of A(2B) receptors may prevent cardiac remodeling
      associated with hypertension, myocardial infarction, and myocardial reperfusion
      injury after ischemia.

PMID- 11230363
TI  - Expression and function of peroxisome proliferator-activated receptor-gamma in
      mesangial cells.
AB  - P:eroxisome proliferator-activated receptor-gamma (PPARgamma) is a novel nuclear
      receptor, which enhances insulin-mediated glucose uptake. Ligands to PPARgamma
      are currently used as therapy for type II diabetes. Using Western blot analysis,
      RNase protection assay, and immunostaining, we identified the presence of
      PPARgamma message and protein in cultured primary rat mesangial cells.
      Electrophoretic mobility of a labeled PPARgamma response element (PPRE) was
      retarded in the presence of mesangial cell nuclear extract, suggesting that
      PPARgamma is functional in these cells. The addition of unlabeled PPRE
      efficiently competed away the PPARgamma-PPRE protein complex, confirming
      specificity of binding of the PPARgamma to the PPRE. PPARgamma ligands
      rosiglitazone (1 to 10 micromol/L) and troglitazone (1 to 10 micromol/L)
      inhibited platelet-derived growth factor-induced DNA synthesis, measured as
      bromodeoxyuridine incorporation (P<0.01). This inhibition was dose dependent.
      When administered in antidiabetic doses to streptozotocin-induced diabetic rats,
      troglitazone substantially normalized albumin excretion at 3 months (from 687.1
      to 137.6 microgram urinary albumin/mg creatinine, P:<0.05) but did not affect
      hyperglycemia or blood pressure in this model. This treatment also decreased
      glomerular plasminogen activator inhibitor-1 (PAI-1) expression. These data
      suggest that PPARgamma activation may directly attenuate diabetic glomerular
      disease, possibly by inhibiting mesangial growth, which occurs early in the
      process of diabetic nephropathy, or by inhibiting PAI-1 expression. PAI-1
      inhibits the activation of plasmin and matrix metalloproteinase, which degrade
      extracellular matrix in the glomerulus. Excess glomerular PAI-1 allows the
      accumulation of extracellular matrix, leading to glomerulosclerosis. These
      results have therapeutic implications for diabetic nephropathy as well as for
      proliferative mesangial diseases of the kidney.

PMID- 11230364
TI  - Nerve growth factor enhances calcitonin gene-related peptide expression in the
      spontaneously hypertensive rat.
AB  - Calcitonin gene-related peptide (CGRP) expression is markedly reduced in dorsal
      root ganglia neurons in the spontaneously hypertensive rat (SHR). This decrease
      in such a potent vasodilator may contribute to the elevated blood pressure.
      Therefore, the purpose of this study was to determine whether stimulation of
      neuronal CGRP expression in SHR, by means of the administration of nerve growth
      factor, would lower the blood pressure. Nerve growth factor (10 nmol/L per kg/d,
      IP) was given to 12-week SHR (n=8 to 11/group) once a day for 1, 3, and 7 days.
      Control SHR received vehicle only. All rats were instrumented for CGRP receptor
      antagonist (CGRP(8-37)) administration (intravenous) and mean arterial pressure
      recording. Both the 1- and 3-day NGF treatments lowered the mean arterial
      pressure to 147+/-5 and 147+/-3 mm Hg, respectively, compared with controls
      (166+/-3 mm Hg). However, by day 7, the mean arterial pressure had returned to
      control levels (169+/-5 mm Hg). CGRP(8-37) administration produced a significant
      mean arterial pressure increase in all 3 nerve growth factor-treated groups (14+/
      2, 10+/-2, and 13+/-2 mm Hg). CGRP mRNA levels in dorsal root ganglia were
      increased in the 3 neurotrophin-treated groups, whereas CGRP peptide content was
      higher at days 3 and 7. Therefore, nerve growth factor treatment of SHR can
      enhance neuronal CGRP expression. At days 1 and 3, nerve growth factor produces a
      depressor response that is primarily mediated by CGRP as evidenced by the pressor
      effect of CGRP(8-37.) At day 7, CGRP also plays a counterregulatory role, even
      though the mean arterial pressure has returned to control levels. This finding
      may result from a nerve growth factor-mediated upregulation of a pressor system
      that counteracts the hypotensive actions of CGRP. Thus, these data suggest that
      the decreased production of CGRP in SHR could contribute to the hypertension.

PMID- 11230365
TI  - Long-term glucose infusion increases arterial pressure in dogs with
      cyclooxygenase-2 inhibition.
AB  - A series of studies has shown that long-term infusion of insulin and glucose does
      not increase mean arterial pressure (MAP) in dogs, but we have shown that the
      same infusion protocol or infusion of glucose alone increases arterial pressure
      in rats. This study tested the hypothesis that infusing glucose alone in dogs,
      with all insulin derived from endogenous secretion, would increase arterial
      pressure. Because fructose feeding in dogs also has been shown not to cause
      hypertension and because we have shown that prostaglandin production increases
      during insulin and glucose infusion, this study also tested whether
      prostaglandins prevent the pressor response in dogs. Dogs were instrumented and
      assigned in random crossover design to long-term cyclooxygenase-2 (COX-2)
      inhibition. After baseline measurements, glucose was infused in all dogs for 6
      days ( approximately 500 g/d IV). Plasma insulin increased 3- to 4-fold and blood
      glucose increased significantly in both groups. The MAP (measured 24 h/d)
      response in control dogs was variable but on average tended to increase, although
      not significantly. In the dogs with COX-2 inhibition, however, MAP increased
      significantly to a peak of 9+/-2 mm Hg and an average of 6+/-1 mm Hg above
      control. There was significant sodium and volume retention during glucose
      infusion and a significant increase in glomerular filtration rate, but there were
      no between-group differences. Plasma renin activity increased only in the control
      group. This is the first study to report a long-term pressor response with
      glucose infusion and hyperinsulinemia in dogs, and it suggests that the inability
      to detect this relationship previously was due to prostaglandins.

PMID- 11230366
TI  - C825T polymorphism of the G protein beta(3)-subunit and antihypertensive response
      to a thiazide diuretic.
AB  - The T allele of the C825T polymorphism of the gene encoding the beta(3)-subunit
      of G proteins has been associated with increased sodium-hydrogen exchange and low
      renin in patients with essential hypertension. To assess its association with
      blood pressure response to diuretic therapy, we measured the C825T polymorphism
      in 197 blacks (134 men, 63 women) and 190 non-Hispanic whites (76 men, 114 women)
      with essential hypertension (mean+/-SD age 48+/-7 years), who underwent
      monotherapy with hydrochlorothiazide for 4 weeks. Mean declines in systolic and
      diastolic blood pressures were 6+/-2 (P:<0.001) and 5+/-1 (P:<0.001) mm Hg
      greater, respectively, in TT than in CC homozygotes. Responses in heterozygotes
      were intermediate between the homozygous groups. Other univariate predictors of
      greater blood pressure responses included black race, female gender, higher
      pretreatment blood pressure, older age, lower waist-to-hip ratio, and measures of
      lower renin-angiotensin-aldosterone system activity. After the effects of the
      other predictors were considered, the TT genotype remained a significant
      predictor of greater declines in systolic and diastolic blood pressures. Thus,
      the C825T polymorphism of the G protein beta(3)-subunit may help identify
      patients with essential hypertension who are more responsive to diuretic therapy.

PMID- 11230367
TI  - Workshop: endothelial cell dysfunction leading to diabetic nephropathy : focus on
      nitric oxide.
AB  - Clinical manifestations of diabetic nephropathy are an expression of diabetic
      microangiopathy. This review revisits the previously proposed Steno hypothesis
      and advances our hypothesis that development of endothelial cell dysfunction
      represents a common pathophysiological pathway of diabetic complications.
      Specifically, the ability of glucose to scavenge nitric oxide is proposed as the
      initiation phase of endothelial dysfunction. Gradual accumulation of advanced
      glycated end products and induction of plasminogen activator inhibitor-1,
      resulting in the decreased expression of endothelial nitric oxide synthase and
      reduced generation of nitric oxide, are proposed to be pathophysiologically
      critical for the maintenance phase of endothelial dysfunction. The proposed
      conceptual shift toward the role of endothelial dysfunction in diabetic
      complications may provide new strategies for their prevention.

PMID- 11230368
TI  - Dipping status may be determined by nocturnal urination.
AB  - Nondipping, ie, failure to reduce blood pressure by >/=10% during the night, is
      considered an important prognostic variable of 24-hour ambulatory blood pressure
      monitoring. However, some people wake up at night to urinate. Usually, 24-hour
      ambulatory blood pressure monitoring-derived blood pressure includes these rises
      in the nighttime blood pressure mean. We identified 97 subjects undergoing 24
      hour ambulatory blood pressure monitoring who reported waking up at night to
      urinate. We assessed the 24-hour ambulatory blood pressure monitoring first using
      total daytime and total nighttime means and then using actual daytime awake and
      nighttime asleep (as reported by the patient) means. Nocturnal decline in blood
      pressure was 14.4+/-8.5/11.8+/-6.1 mm Hg with the first method and 17.1+/
      8.3/13.8+/-5.9 mm Hg with the second one (P<0.00001). Although the absolute
      difference between the nocturnal blood pressure declines calculated by the 2
      methods was small, the effect on nocturnal dip was profound. Average systolic
      blood pressure dipping was 10.1% by the total day-total night method and 12.0% by
      the actual day awake-night asleep method (P</=0.00001), and that of diastolic
      blood pressure was 14.2% and 16.7%, respectively (P</=0.00001). The prevalence of
      systolic blood pressure nondipping decreased from 42.2% by the first method to
      31.9% by the second method (P</=0.0056), and that of diastolic blood pressure
      nondipping decreased from 22.6% to 11.3% (P</=0.00001). Inclusion of awake blood
      pressure measurements during the night obscured the normal dipping pattern in
      people who woke up to urinate. Thus, taking into account people's actual behavior
      increases the accuracy of the results.

PMID- 11230369
TI  - Renal interstitial atp responses to changes in arterial pressure during
      alterations in tubuloglomerular feedback activity.
AB  - We recently demonstrated a direct relationship between autoregulation-related
      changes in renal vascular resistance (RVR) and renal interstitial ATP
      concentrations. To assess the possible role for extracellular ATP in the
      regulation of tubuloglomerular feedback (TGF)-mediated autoregulatory adjustments
      in RVR, renal interstitial ATP concentrations were measured with microdialysis
      probes in anesthetized dogs at different renal arterial pressures (RAPs) within
      the autoregulatory range during augmented and diminished activity of the TGF
      mechanism. Stepwise reductions in RAP from ambient pressure (129+/-3 mm Hg) to
      102+/-2 mm Hg (step 1) and 75+/-1 mm Hg (step 2) resulted in significant
      decreases in ATP concentrations from 9.0+/-0.8 to 6.3+/-0.6 nmol/L in step 1 and
      to 4.2+/-0.5 nmol/L in step 2. Changes in RVR were highly correlated with changes
      in ATP concentrations (r=0.86, P<0.001, n=12). Acetazolamide (100 microgram. kg(
      1). min(-1), n=6), which increases solute delivery to the macula densa, thus
      augmenting TGF activity, significantly decreased renal blood flow (RBF) by -16+/
      2% and glomerular filtration rate (GFR) by -22+/-4% and increased ATP
      concentrations from 8.4+/-0.7 to 15.5+/-1.4 nmol/L. Although basal RBF and GFR
      levels were reduced by the acetazolamide infusion, autoregulation efficiency was
      maintained, and interstitial ATP concentrations were significantly decreased in
      response to reductions in RAP by -36+/-4% in step 1 and by -54+/-2% in step 2.
      The relationship between changes in RVR and interstitial ATP concentrations was
      preserved during acetazolamide treatment (r=0.80, P<0.01). Inhibition of the TGF
      mechanism by furosemide significantly increased RBF by 33+/-6% and GFR by 13+/-2%
      and decreased ATP concentrations from 8.9+/-1.4 to 5.0+/-0.8 nmol/L (n=6).
      Furosemide caused marked impairment of RBF and GFR autoregulatory efficiency (by 
      14+/-3% and -11+/-3% in step 1 and by -26+/-2% and -18+/-4% in step 2,
      respectively). In the furosemide-treated kidneys, interstitial ATP levels
      remained low and were not altered during reductions in RAP (4.7+/-0.7 nmol/L in
      step 1 and 4.7+/-0.8 nmol/L in step 2), and changes in RVR did not exhibit a
      correlation with changes in ATP concentrations (r=0.22, P=0.30). These data
      support the hypothesis that extracellular ATP contributes to autoregulatory
      adjustments in RVR that are mediated by changes in activity of the TGF mechanism.

PMID- 11230370
TI  - Workshop: excess growth and apoptosis: is hypertension a case of accelerated
      aging of cardiovascular cells?
AB  - Several groups including ours have demonstrated cardiac hyperplasia in neonates
      from genetically hypertensive rat strains. We have shown that similar problems
      exist in the kidney as well. More recently, we found that excessive heart and
      kidney weight is neonatally related to inhibition of apoptosis. Using recombinant
      inbred strains derived from a reciprocal cross between Brown Norway and
      spontaneously hypertensive rat progenitor strains, we mapped the inhibition of
      neonatal apoptosis to 2 distinct loci on chromosomes 1 (Myl 2) and 18 (Abrb 2).
      Positional candidate genes at these loci are being explored. These studies have
      also demonstrated that the loci determining kidney and heart weights in neonates
      are distinct from those determining increased organ weight in adults. The impact
      of blood pressure per se is also divergent because adult kidney weight is
      negatively correlated whereas heart weight is positively correlated with it.
      Analyses by extremes of low and high percentiles from fetal life to adulthood
      identified a single locus determining heart weight at Acaa on chromosome 8 in
      newborn (P=0.0003) and adult (P=0.016) rats. The Acaa region contains a DNA
      mismatch repair gene (hMLH1). The kinetics of neonatal growth through adulthood
      by prelabeling DNA with [(3)H]thymidine in pregnant mares showed that although
      the growth process is complex and nonlinear in the kidney of hypertensive rats,
      there is an increased turnover of cells, that is, reduced half-life of DNA. This
      observation is supported by the presence of shorter telomere fragments in kidneys
      of spontaneously hypertensive rats. These studies suggest that cardiovascular
      cells from hypertensive animals are subject to accelerated turnover, potentially
      leading to their accelerated aging.

PMID- 11230371
TI  - Workshop: hypertension and cardiovascular risk factors: role of the angiotensin
      II-nitric oxide interaction.
AB  - Vascular upregulation of nitric oxide (NO) is an adaptive response to increased
      blood pressure that may help in the prevention of end-organ damage. Differences
      in cardiovascular and renal morbidity and mortality in hypertensive patients may
      result, at least in part, from individual variations in endothelial function in
      response to the hemodynamic workload of hypertension. A functional feedback
      balance exists between both angiotensin (Ang) II and NO under normal conditions.
      The NO-Ang II imbalance may not explain all the vascular pathophysiology of
      hypertension, but it certainly appears to be an important component. In
      hypertension, salt sensitivity, whether primary (ie, certain populations in the
      United States and Japan) or secondary (ie, aging, type II diabetes), appears to
      be a marker of increased cardiovascular and renal risk that is often linked to a
      decreased bioactivity of NO. In diabetes and atherosclerosis, NO-dependent
      vascular relaxation is impaired and can be restored by decreasing the synthesis
      and/or blocking the action of Ang II. An understanding of the relations between
      hypertension, cardiovascular risk factors, end-organ damage, and the NO-Ang II
      axis leads one to believe that the combination of therapeutic agents capable of
      reinstating the homeostatic balance of these vasoactive molecules within the
      vessel wall would be most effective in preventing or arresting end-organ disease.

PMID- 11230373
TI  - Long-term antioxidant administration attenuates mineralocorticoid hypertension
      and renal inflammatory response.
AB  - We previously reported increased monocyte/macrophage infiltration, reactive
      oxygen species accumulation, and nuclear factor-kappaB (NF-kappaB) activation in
      mineralocorticoid (deoxycorticosterone acetate [DOCA]) hypertensive rats. We
      tested the hypothesis that prolonged antioxidant administration inhibits
      superoxide accumulation, lowers blood pressure, and reduces NF-kappaB activation
      in DOCA-salt hypertensive rats. DOCA rats exhibited a significant increase in
      systolic blood pressure compared with sham rats. Aortic rings from DOCA rats
      exhibited increased superoxide (O(2)(-)) production compared with sham rats. In
      addition, the treatment of DOCA rats with pyrrolidinedithiocarbamate (PDTC) or 4
      hydroxy-2,2,6,6-tetramethyl piperidinoxyl (Tempol) caused a significant decrease
      in systolic blood pressure and aortic superoxide accumulation.
      Monocyte/macrophage infiltration was also significantly decreased in DOCA rats
      treated with PDTC or Tempol compared with untreated DOCA rats. NF-kappaB-binding
      activity was significantly greater in untreated DOCA rats than in either sham
      rats or PDTC- or Tempol-treated DOCA rats. Also, DOCA rats treated with Tempol
      exhibited no significant difference in NF-kappaB-binding activity compared with
      sham. These results suggest that antioxidants attenuate systolic blood pressure,
      suppress renal NF-kappaB-binding activity, and partly alleviate renal
      monocyte/macrophage infiltration in DOCA-salt hypertension.

PMID- 11230372
TI  - Combination of hypercholesterolemia and hypertension augments renal function
      abnormalities.
AB  - Hypercholesterolemia and hypertension are both risk factors for end-stage renal
      disease. This study was designed to examine whether their coexistence augmented
      impairment in renal function and redox status. Regional renal hemodynamics and
      function in response to vasoactive challenges with acetylcholine or sodium
      nitroprusside were quantified by using electron-beam computed tomography in pigs
      after 12 weeks of either a normal (n=10) or hypercholesterolemic (n=10) diet,
      renovascular hypertension (n=7), or combined hypercholesterolemia+hypertension
      (n=6). The hypercholesterolemic and hypercholesterolemic+hypertensive groups had
      significantly increased serum cholesterol levels, whereas in the hypertensive and
      hypercholesterolemic+hypertensive groups, mean arterial pressure was
      significantly elevated compared with the group fed a normal diet. Basal regional
      renal perfusion and glomerular filtration rates were similar among the groups. In
      response to acetylcholine, cortical perfusion increased in normal animals (15.6+/
      4.7%, P=0.002) but not in hypercholesterolemic or hypertensive animals (8.0+/
      7.4% and 8.2+/-5.9%, respectively; P>0.05). Moreover, in the
      hypercholesterolemic+hypertensive group, cortical perfusion response was further
      attenuated (2.5+/-4.8%, P=0.02) and significantly different from the group fed a
      normal diet (P<0.05). The response to sodium nitroprusside followed a similar
      pattern, and the impairment was augmented in the
      hypercholesterolemic+hypertensive group. The functional abnormalities in
      hypercholesterolemia or hypertension were associated with a decrease in systemic
      and/or renal tissue levels of oxygen radical scavengers that was again
      accentuated in hypercholesterolemia+hypertension. These results demonstrate that
      concurrent hypercholesterolemia and hypertension have a greater detrimental
      effect on renal perfusion responses compared with hypercholesterolemia or
      hypertension alone, associated with a marked pro-oxidant shift in redox status.
      These effects may potentially augment renal functional impairment and play a role
      in the initiation and progression of renal injury in hypertension and
      atherosclerosis.

PMID- 11230374
TI  - Mineralocorticoid receptor affects AP-1 and nuclear factor-kappab activation in
      angiotensin II-induced cardiac injury.
AB  - Aldosterone is implicated in cardiac hypertrophy and fibrosis. We tested the role
      of the mineralocorticoid receptor in a model of angiotensin II-induced cardiac
      injury. We administered spironolactone (SPIRO; 20 mg. kg(-1). d(-1)), valsartan
      (VAL; 10 mg. kg(-1). d(-1)), or vehicle to rats double transgenic for the human
      renin and angiotensinogen genes (dTGR). We investigated basic fibroblast growth
      factor (bFGF), platelet-derived growth factor, transforming growth factor
      beta(1), and the transcription factors AP-1 and nuclear factor (NF)-kappaB. We
      used immunohistochemistry, electrophoretic mobility shift assays, and TaqMan RT
      PCR. Untreated dTGR developed hypertension, cardiac hypertrophy, vasculopathy,
      and fibrosis with a 50% mortality rates at 7 weeks. SPIRO and VAL prevented death
      and reversed cardiac hypertrophy, while only VAL normalized blood pressure. Both
      drugs prevented vasculopathy. bFGF was markedly upregulated in dTGR, whereas
      platelet-derived growth factor-B and transforming growth factor-beta(1) were
      little changed. VAL and SPIRO suppressed this upregulation. Both AP-1 and NF
      kappaB were activated in dTGR compared with controls. VAL and SPIRO reduced both
      transcription factors and reduced bFGF, collagen I, fibronectin, and laminin in
      the interstitium. These findings show that aldosterone promotes hypertrophy,
      cardiac remodeling, and fibrosis, independent of blood pressure. The effects
      involve AP-1, NF-kappaB, and bFGF. Mineralocorticoid receptor blockade
      downregulates these effectors and reduces angiotensin II-induced cardiac damage.

PMID- 11230375
TI  - Antifibrotic effects of N-acetyl-seryl-aspartyl-Lysyl-proline on the heart and
      kidney in aldosterone-salt hypertensive rats.
AB  - N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) inhibits not only hematopoietic
      cell proliferation but also fibroblast proliferation and collagen synthesis in
      vitro. Ac-SDKP also prevents collagen deposition and cell proliferation in the
      left ventricle (LV) in rats with renovascular hypertension (renin dependent).
      However, it is not clear whether Ac-SDKP has similar effects in a model of renin
      independent hypertension (aldosterone-salt). Using a hypertensive rat model of
      cardiac and renal fibrosis created by chronic elevation of circulating
      aldosterone (ALDO) levels, we examined the effect of Ac-SDKP on blood pressure,
      cardiac and renal fibrosis and hypertrophy, and proliferating cell nuclear
      antigen (PCNA) expression in the LV and left kidney. Uninephrectomized rats were
      divided into 4 groups: (1) controls that received tap water, (2) rats that
      received ALDO (0.75 microgram/h SC) and 1% NaCl/0.2% KCl in drinking water (ALDO
      salt), (3) rats that received ALDO-salt plus Ac-SDKP 400 microgram. kg(-1). day(
      1) SC, and (4) rats that received ALDO-salt plus Ac-SDKP 800 microgram. kg(-1).
      d(-1) SC. After 6 weeks of treatment, the ALDO-salt group was found to have
      significantly increased blood pressure with decreased body weight and plasma
      renin concentration (P<0.05), LV and renal hypertrophy as well as renal injury,
      significantly increased collagen content in both ventricles and kidney as well as
      increased collagen volume fraction in the LV (P<0.0001), and significantly
      increased interstitial and perivascular PCNA-positive cells in the LV and kidney
      (P<0.0001). Ac-SDKP at 800 microgram. kg(-1). d(-1) markedly prevented cardiac
      and renal fibrosis (P<0.005) without affecting blood pressure or organ
      hypertrophy. It also suppressed PCNA expression in the LV and kidney in a dose
      dependent manner. We concluded that Ac-SDKP prevents increased collagen
      deposition and cell proliferation in the heart and kidney in ALDO-salt
      hypertensive rats. Because ACE inhibitors increase plasma and tissue Ac-SDKP and
      decrease cardiac and renal fibrosis, we speculate that Ac-SDKP may participate in
      the antifibrotic effect of ACE inhibitors.

PMID- 11230376
TI  - Aldosterone receptor antagonism normalizes vascular function in liquorice-induced
      hypertension.
AB  - The enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD2) provides
      mineralocorticoid receptor specificity for aldosterone by metabolizing
      glucocorticoids to their receptor-inactive 11-dehydro derivatives. The present
      study investigated the effects of the aldosterone receptor antagonists
      spironolactone and eplerenone on endothelial function in liquorice-induced
      hypertension. Glycyrrhizic acid (GA), a recognized inhibitor of 11beta-HSD2, was
      supplemented to the drinking water (3 g/L) of Wistar-Kyoto rats over a period of
      21 days. From days 8 to 21, spironolactone (5.8+/-0.6 mg. kg(-1). d(-1)),
      eplerenone (182+/-13 mg. kg(-1). d(-1)), or placebo was added to the chow (n=7
      animals per group). Endothelium-dependent or -independent vascular function was
      assessed as the relaxation of preconstricted aortic rings to acetylcholine or
      sodium nitroprusside, respectively. In addition, aortic endothelial nitric oxide
      synthase (eNOS) protein content, nitrate tissue levels, and endothelin-1 (ET-1)
      protein levels were determined. GA increased systolic blood pressure from 142+/-8
      to 185+/-9 mm Hg (P<0.01). In the GA group, endothelium-dependent relaxation was
      impaired compared with that in controls (73+/-6% versus 99+/-5%), whereas
      endothelium-independent relaxation remained unchanged. In the aortas of 11beta
      HSD2-deficient rats, eNOS protein content and nitrate tissue levels decreased
      (1114+/-128 versus 518+/-77 microgram/g protein, P<0.05). In contrast, aortic ET
      1 protein levels were enhanced by GA (308+/-38 versus 497+/-47 pg/mg tissue,
      P<0.05). Both spironolactone and eplerenone normalized blood pressure in animals
      on GA (142+/-9 and 143+/-9 mm Hg, respectively, versus 189+/-8 mm Hg in the
      placebo group; P<0.01), restored endothelium-dependent relaxation (96+/-3% and
      97+/-3%, respectively, P<0.01 versus placebo), blunted the decrease in vascular
      eNOS protein content and nitrate tissue levels, and normalized vascular ET-1
      levels. This is the first study to demonstrate that aldosterone receptor
      antagonism normalizes blood pressure, prevents upregulation of vascular ET-1,
      restores NO-mediated endothelial dysfunction, and thus, may advance as a novel
      and specific therapeutic approach in 11beta-HSD2-deficient hypertension.

PMID- 11230377
TI  - K(+) depletion and the progression of hypertensive disease or heart failure. The
      pathogenic role of diuretic-induced aldosterone secretion.

PMID- 11230379
TI  - Educational instruction on a hospital information system for medical students
      during their surgical rotations.
AB  - OBJECTIVE: To evaluate the benefit, for medical students on their surgical
      rotations, of real-time educational instruction during order entry on a hospital
      information system. DESIGN: Prospective controlled trial. INTERVENTION: Access to
      educational information during computerized order entry. SUBJECTS: Medical
      students in their final year at the University of Calgary. MAIN OUTCOMES:
      Attainment of the surgery rotation educational objectives, as measured by
      performance on a multiple-choice examination. METHODS: Before they began their
      surgical rotations, students at two hospitals took a multiple-choice examination
      to measure their knowledge of surgery. One hospital had an information system
      with computerized order entry; students at this hospital had access, while
      composing orders, to educational material on the system. The other hospital did
      not have an information system; students there wrote orders on a paper chart. At
      the end of the rotation, all students took another multiple-choice examination.
      RESULTS: Of 50 eligible students, 45 agreed to participate in the project, 21 in
      the treatment group and 24 in the control group. Pre-rotation scores were similar
      for the two groups (43 percent in the treatment group and 40 percent in the
      control group; SD, 10 percent). Post-rotation scores were identical for the two
      groups (65 percent in the treatment group and 65 percent in the control group;
      SD, 12 percent). A t-test analysis revealed no significant difference in
      performance on the examinations between the two groups. CONCLUSION: This study
      did not demonstrate a learning advantage for medical students who have access to
      educational material on a hospital information system.

PMID- 11230380
TI  - Clinicians' response to computerized detection of infections.
AB  - OBJECTIVE: To analyze whether computer-generated reminders about infections could
      influence clinicians' practice patterns and consequently improve the detection
      and management of nosocomial infections. DESIGN: The conclusions produced by an
      expert system developed to detect and manage infections were presented to the
      attending clinicians in a pediatric hospital to determine whether this
      information could improve detection and management. Clinician interventions were
      compared before and after the implementation of the system. MEASUREMENTS: The
      responses of the clinicians (staff physicians, physician assistants, and nurse
      practitioners) to the reminders were determined by review of paper medical
      charts. Main outcome measures were the number of suggestions to treat and manage
      infections that were followed before and after the implementation of COMPISS
      (Computerized Pediatric Infection Surveillance System). The clinicians' opinions
      about the system were assessed by means of a paper questionnaire distributed
      following the experiment. RESULTS: The results failed to show a statistical
      difference between the clinicians' treatment strategies before and after
      implementation of the system (P: > 0.33 for clinicians working in the emergency
      room and P: > 0.45 for clinicians working in the pediatric intensive care unit).
      The questionnaire results showed that the respondents appreciated the information
      presented by the system. CONCLUSION: The computer-generated reminders about
      infections were unable to influence the practice patterns of clinicians. The
      methodologic problems that may have contributed to this negative result are
      discussed.

PMID- 11230381
TI  - Progress with formalization in medical informatics?
AB  - The prevailing view of medical informatics as a primarily subservient discipline
      in health care is challenged. Developments in both general informatics and
      medical informatics are described to identify desirable properties of modeling
      languages and tools needed to solve key problems in the application field. For
      progress in medical informatics, it is considered essential to develop far more
      formal modeling languages, modeling techniques, and tools. A major aim of this
      development should be to expel ambiguity from concepts essential to medicine,
      positioning medical informatics "at the heart of health care."

PMID- 11230382
TI  - Domain-constrained generation of clinical condition sets to help test computer
      based clinical guidelines.
AB  - The paper describes T/Gen, a prototype computer-based tool designed to help
      maintain the knowledge in a computer-based clinical practice guideline that
      provides patient-specific recommendations. T/Gen takes as input a set of clinical
      conditions to which a guideline must react, and allows the user to specify domain
      specific constraints as to which combinations of conditions do not make sense or
      do not need to be exhaustively tested against one another. T/Gen automatically
      generates constrained sets of combinations of clinical conditions, each
      corresponding to a clinical case (or to several closely related clinical cases)
      that can be used to help test the computer-based guideline. The combinations can
      be used to test the guideline logic using T/Gen's built-in logic interpreter, or
      to generate a set of test cases for use in testing an operational guideline
      system. T/Gen has been developed and tested with five pilot guidelines, for two
      childhood immunization series, for influenza vaccination, for primary thyroid
      screening, and for embryo transplantation. The paper describes how T/Gen's
      approach is implemented for the five pilot guidelines, outlines the current
      status and future directions of the project, and discusses the design issues that
      arose in the course of carrying out the work.

PMID- 11230383
TI  - Requirements for medical modeling languages.
AB  - OBJECTIVE: The development of tailor-made domain-specific modeling languages is
      sometimes desirable in medical informatics. Naturally, the development of such
      languages should be guided. The purpose of this article is to introduce a set of
      requirements for such languages and show their application in analyzing and
      comparing existing modeling languages. DESIGN: The requirements arise from the
      practical experience of the authors and others in the development of modeling
      languages in both general informatics and medical informatics. The requirements
      initially emerged from the analysis of information modeling techniques. The
      requirements are designed to be orthogonal, i.e., one requirement can be violated
      without violation of the others. RESULTS: The proposed requirements for any
      modeling language are that it be "formal" with regard to syntax and semantics,
      "conceptual," "expressive," "comprehensible," "suitable," and "executable." The
      requirements are illustrated using both the medical logic modules of the Arden
      Syntax as a running example and selected examples from other modeling languages.
      CONCLUSION: Activity diagrams of the Unified Modeling Language, task structures
      for work flows, and Petri nets are discussed with regard to the list of
      requirements, and various tradeoffs are thus made explicit. It is concluded that
      this set of requirements has the potential to play a vital role in both the
      evaluation of existing domain-specific languages and the development of new ones.

PMID- 11230385
TI  - Comparison of information processing technologies.
AB  - OBJECTIVE: To examine the type of information obtainable from scientific papers,
      using three different methods for the extraction, organization, and preparation
      of literature reviews. DESIGN: A set of three review papers was identified, and
      the ideas represented by the authors of those papers were extracted. The 161
      articles referenced in those three reviews were then analyzed using 1) a
      formalized data extraction approach, which uses a protocol-driven manual process
      to extract the variables, values, and statistical significance of the stated
      relationships; and 2) a computerized approach known as "Idea Analysis," which
      uses the abstracts of the original articles and processes them through a computer
      software program that reads the abstracts and organizes the ideas presented by
      the authors. The results were then compared. The literature focused on the human
      papillomavirus and its relationship to cervical cancer. RESULTS: Idea Analysis
      was able to identify 68.9 percent of the ideas considered by the authors of the
      three review papers to be of importance in describing the association between
      human papillomavirus and cervical cancer. The formalized data extraction
      identified 27 percent of the authors' ideas. The combination of the two
      approaches identified 74.3 percent of the ideas considered important in the
      relationship between human papillomavirus and cervical cancer, as reported by the
      authors of the three review articles. CONCLUSION: This research demonstrated that
      both a technically derived and a computer derived collection, categorization, and
      summarization of original articles and abstracts could provide a reliable, valid,
      and reproducible source of ideas duplicating, to a major degree, the ideas
      presented by subject specialists in review articles. As such, these tools may be
      useful to experts preparing literature reviews by eliminating many of the
      clerical-mechanical features associated with present-day scientific text
      processing.

PMID- 11230384
TI  - Studying the human-computer-terminology interface.
AB  - OBJECTIVE: To explore the use of an observational, cognitive-based approach for
      differentiating between successful, suboptimal, and failed entry of coded data by
      clinicians in actual practice, and to detect whether causes for unsuccessful
      attempts to capture true intended meaning were due to terminology content,
      terminology representation, or user interface problems. DESIGN: Observational
      study with videotaping and subsequent coding of data entry events in an
      outpatient clinic at New York Presbyterian Hospital. PARTICIPANTS: Eight
      attending physicians, 18 resident physicians, and 1 nurse practitioner, using the
      Medical Entities Dictionary (MED) to record patient problems, medications, and
      adverse reactions in an outpatient medical record system. MEASUREMENTS:
      Classification of data entry events as successful, suboptimal, or failed, and
      estimation of cause; recording of system response time and total event time.
      RESULTS: Two hundred thirty-eight data entry events were analyzed; 71.0 percent
      were successful, 6.3 percent suboptimal, and 22.7 percent failed; unsuccessful
      entries were due to problems with content in 13.0 percent of events,
      representation problems in 10.1 percent of events, and usability problems in 5.9
      percent of events. Response time averaged 0.74 sec, and total event time averaged
      40.4 sec. Of an additional 209 tasks related to drug dose and frequency terms, 94
      percent were successful, 0.5 percent were suboptimal, and 6 percent failed, for
      an overall success rate of 82 percent. CONCLUSIONS: Data entry by clinicians
      using the outpatient system and the MED was generally successful and efficient.
      The cognitive-based observational approach permitted detection of false-positive
      (suboptimal) and false-negative (failed due to user interface) data entry.

PMID- 11230386
TI  - Estimating software development costs for a patient multimedia education project.
AB  - The authors compare alternative methods of cost estimation for a patient
      multimedia education (PME) program, using a computerized weight-reduction PME
      project as an example. Data from the project planning and budgeting process and
      actual costs of the completed project are analyzed retrospectively to calculate
      three different estimates-pre-work, post-work, and actual work. Three traditional
      methods of estimating the cost of computer programs (the lines-of-code, function
      point, and task ratio analyses) underestimate costs in this example. A commercial
      program (Cost Xpert) that calculates the cost of developing a graphical user
      interface provided a better estimate, as did a tally reflecting the complexity
      and quality of media material in the project.

PMID- 11230387
TI  - Publication bias in medical informatics.

PMID- 11230388
TI  - Get both the medicine and the informatics right.

PMID- 11230391
TI  - Comparison between the LCx Probe system and the COBAS AMPLICOR system for
      detection of Chlamydia trachomatis and Neisseria gonorrhoeae infections in
      patients attending a clinic for treatment of sexually transmitted diseases in
      Amsterdam, The Netherlands.
AB  - Two assays for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae
      were compared: the LCx Probe system (the LCx system; Abbott Diagnostic
      Laboratories, North Chicago, Ill.) and the COBAS AMPLICOR C. trachomatis/N.
      gonorrhoeae system (the COBAS AMPLICOR system; Roche Diagnostic Systems,
      Branchburg, N.J.). Endocervical swab specimens, male urethral swab specimens, and
      female and male urine specimens were collected from 503 female and 498 male
      visitors attending a sexually transmitted diseases clinic in Amsterdam, The
      Netherlands. Prevalences for C. trachomatis were 12.5% (63 of 503) and 10.0% (50
      of 498) in females and males, respectively. The prevalences for N. gonorrhoeae
      were 1.2% (6 of 503) and 4.2% (21 of 498) in females and males, respectively.
      Both assays showed high values for sensitivity and specificity with regard to the
      detection of C. trachomatis in endocervical swab specimens, male urethral swab
      specimens, and female and male urine specimens. The sensitivities for the LCx
      system were 92.1, 90.0, 88.9, and 94.0% for each type of specimen, respectively;
      and the sensitivies for the COBAS AMPLICOR system were 96.8, 98.0, 82.5, and
      92.0% for each type of specimen, respectively. Specificities ranged between 98.4
      and 100%. The sensitivity of the LCx system for the detection of N. gonorrhoeae
      was 100% for female cervical swab and urine specimens and male urethral swab
      specimens, while for male urine specimens the sensitivity was 95.2%; the
      specificity was 100% for all types of specimens. For the detection of N.
      gonorrhoeae by the COBAS AMPLICOR assay, the sensitivity for female cervical swab
      and male urethral swab specimens was 100%, that for female urine specimens was
      66.7%, and that for male urine specimens was 95.2%. However, the predictive
      values of a positive test for female cervical swab specimens and urine specimens
      were 31.6 and 36.4%, respectively. Sequence analysis of the amplimers obtained by
      an in-house 16S rRNA PCR of the solely COBAS AMPLICOR system-positive swab
      specimens revealed neither N. gonorrhoeae nor other Neisseria spp. The COBAS
      AMPLICOR assay was considered not suitable for screening for infections with N.
      gonorrhoeae. If this assay is used for detection of N. gonorrhoeae, confirmation
      of positive results by a reliable test is mandatory.

PMID- 11230392
TI  - Rotavirus strain diversity in Blantyre, Malawi, from 1997 to 1999.
AB  - In a 2-year study of viral gastroenteritis in children in Blantyre, Malawi, the
      diversity of rotavirus strains was investigated by using electropherotyping,
      reverse transcription-PCR amplification of the VP7 and VP4 genes (G and P
      genotyping), and nucleotide sequencing. Of 414 rotavirus strains characterized,
      the following strain types were identified: P[8], G1 (n = 111; 26.8%); P[6], G8
      (n = 110; 26.6%); P[8], G3 (n = 93; 22.5%); P[4], G8 (n = 31; 7.5%); P[8], G4 (n
      = 21; 5.1%); P[6], G3 (n = 12; 2.9%); P[6], G1 (n = 7; 1.7%); P[6], G9 (n = 3;
      0.7%); P[6], G4 (n = 3; 0.7%); P[4], G3 (n = 1; 0.2%); and mixed (n = 15; 3.6%).
      While all strains could be assigned a G type, seven strains (1.7%) remained P
      nontypeable. The majority of serotype G8 strains and all serotype G9 strains had
      short electropherotype profiles. All remaining typeable strains had long
      electropherotypes. Divergent serotype G1 rotaviruses, which contained multiple
      base substitutions in the 9T-1 primer binding site, were commonly identified in
      the second year of surveillance. Serotype G2 was not identified. Overall, G8 was
      the most frequently identified VP7 serotype (n = 144; 34.8%) and P[8] was the
      most frequently detected VP4 genotype (n = 227; 54.8%). Partial sequence analysis
      of the VP4 gene of genotype P[8] rotaviruses identified three distinct clusters,
      which predominantly (but not exclusively) comprised strains belonging to a
      distinct VP7 serotype (G1, G3, or G4). As a result of mutations in the 1T-1
      primer binding site, strains belonging to each cluster required a separate primer
      for efficient typing. One cluster, represented by P[8], G4 strain OP354, was
      highly divergent from the established Wa and F45 VP4 P[8] lineages. As is the
      case for some other countries, the diversity of rotaviruses in Malawi implies
      that rotavirus vaccines in development will need to protect against a wider panel
      of serotypes than originally envisioned.

PMID- 11230393
TI  - Dogs as sentinels for human Lyme borreliosis in The Netherlands.
AB  - Serum samples from hunters (n = 440), their hunting dogs (n = 448), and hunters
      without dog ownership (n = 53) were collected in The Netherlands at hunting dog
      trials and were tested for antibodies against Borrelia burgdorferi by a whole
      cell enzyme-linked immunosorbent assay. Additionally, 75 healthy pet dogs were
      tested. The results of this study indicate that the seroprevalence among hunting
      dogs (18%) was of the same order as the seroprevalence among pet dogs (17%) and
      hunters (15%). The seropositivity of a hunting dog was not a significant
      indicator of increased risk of Lyme borreliosis for its owner. No significant
      rise in seroprevalence was found in dogs older than 24 months. This indicated
      that seropositivity after an infection with B. burgdorferi in dogs is rather
      short, approximately 1 year. In humans this is considerably longer but is also
      not lifelong. Therefore, the incidence of B. burgdorferi infections among dogs
      was greater than that among hunters, despite a similar prevalence of
      seropositivity among hunters and their hunting dogs. Because no positive
      correlation was observed between the seropositivity of a hunter and the
      seropositivity of the hunter's dog, direct transfer of ticks between dog and
      hunter does not seem important and owning a dog should not be considered a risk
      factor for Lyme borreliosis.

PMID- 11230394
TI  - Development of a species-specific PCR assay for detection of Leishmania donovani
      in clinical samples from patients with kala-azar and post-kala-azar dermal
      leishmaniasis.
AB  - We have developed a PCR assay that is capable of amplifying kinetoplast DNA
      (kDNA) of Leishmania donovani in a species-specific manner among Old World
      leishmanias. With Indian strains and isolates of L. donovani the assay was
      sensitive enough to detect kDNA in an amount equivalent to a single parasite or
      less. The extreme sensitivity of the assay was reflected in its ability to detect
      parasite DNA from small volumes of peripheral blood of patients with kala-azar
      (KA) and from skin lesions from patients with post-KA dermal leishmaniasis
      (PKDL). A total of 107 clinical leishmaniasis samples were analyzed. Of these 102
      (95.3%) were positive by PCR. The test provided a diagnosis of KA with 96%
      sensitivity using patient whole-blood samples instead of bone marrow or spleen
      aspirates that are obtained by invasive procedures. The assay was also successful
      in the diagnosis of 45 of 48 PKDL cases (93.8%). Cross-reactions with pathogens
      prevalent in the area of endemicity, viz., Mycobacterium tuberculosis,
      Mycobacterium leprae, and Plasmodium spp., could be ruled out. Eighty-one control
      samples, including dermal scrapings from healthy portions of skin from patients
      with PKDL were all negative. Two of twenty controls from the area of endemicity
      were found positive by PCR assay; however, there was a good possibility that
      these two were asymptomatic carriers since they were serologically positive for
      KA. Thus, this PCR assay represents a tool for the diagnosis of KA and PKDL in
      Indian patients in a noninvasive manner, with simultaneous species identification
      of parasites in clinical samples.

PMID- 11230395
TI  - Risk of Mycobacterium tuberculosis transmission in a low-incidence country due to
      immigration from high-incidence areas.
AB  - Does immigration from a high-prevalence area contribute to an increased risk of
      tuberculosis in a low-incidence country? The tuberculosis incidence in Somalia is
      among the highest ever registered. Due to civil war and starvation, nearly half
      of all Somalis have been forced from their homes, causing significant migration
      to low-incidence countries. In Denmark, two-thirds of all tuberculosis patients
      are immigrants, half from Somalia. To determine the magnitude of Mycobacterium
      tuberculosis transmission between Somalis and Danes, we analyzed DNA fingerprint
      patterns of isolates collected in Denmark from 1992 to 1999, comprising >97% of
      all culture-positive patients (n = 3,320). Of these, 763 were Somalian
      immigrants, 55.2% of whom shared identical DNA fingerprint patterns; 74.9% of
      these were most likely infected before their arrival in Denmark, 23.3% were most
      likely infected in Denmark by other Somalis, and 1.8% were most likely infected
      by Danes. In the same period, only 0.9% of all Danish tuberculosis patients were
      most likely infected by Somalis. The Somalian immigrants in Denmark could be
      distributed into 35 different clusters with possible active transmission, of
      which 18 were retrieved among Somalis in the Netherlands. This indicated the
      existence of some internationally predominant Somalian strains causing clustering
      less likely to represent recent transmission. In conclusion, M. tuberculosis
      transmission among Somalis in Denmark is limited, and transmission between
      Somalis and Danes is nearly nonexistent. The higher transmission rates between
      nationalities found in the Netherlands do not apply to the situation in Denmark
      and not necessarily elsewhere, since many different factors may influence the
      magnitude of active transmission.

PMID- 11230396
TI  - Comparative performance of three viral load assays on human immunodeficiency
      virus type 1 (HIV-1) isolates representing group M (subtypes A to G) and group O:
      LCx HIV RNA quantitative, AMPLICOR HIV-1 MONITOR version 1.5, and Quantiplex HIV
      1 RNA version 3.0.
AB  - The performance of the LCx HIV RNA Quantitative (LCx HIV), AMPLICOR HIV-1 MONITOR
      version 1.5 (MONITOR v1.5), and Quantiplex HIV-1 RNA version 3.0 (bDNA v3.0)
      viral load assays was evaluated with 39 viral isolates (3 A, 7 B, 6 C, 4 D, 8 E,
      4 F, 1 G, 4 mosaic, and 2 group O). Quantitation across the assay dynamic ranges
      was assessed using serial fivefold dilutions of the viruses. In addition,
      sequences of gag-encoded p24 (gag p24), pol-encoded integrase, and env-encoded
      gp41 were analyzed to assign group and subtype and to assess nucleotide
      mismatches at primer and probe binding sites. For group M isolates,
      quantification was highly correlated among all three assays. In contrast, only
      the LCx HIV assay reliably quantified group O isolates. The bDNA v3.0 assay
      detected but consistently underquantified group O viruses, whereas the MONITOR
      v1.5 test failed to detect group O viruses. Analysis of target regions revealed
      fewer primer or probe mismatches in the LCx HIV assay than in the MONITOR v1.5
      test. Consistent with the high level of nucleotide conservation is the ability of
      the LCx HIV assay to quantify efficiently human immunodeficiency virus type 1
      group M and the genetically diverse group O.

PMID- 11230397
TI  - Reverse dot blot assay (insertion site typing) for precise detection of sites of
      IS6110 insertion in the Mycobacterium tuberculosis genome.
AB  - We have developed an amplification-based reverse dot blot assay for the detection
      of specific sites of insertion of the Mycobacterium tuberculosis insertion
      sequence IS6110. In this assay, a set of biotin-labeled amplicons representing
      the various copies of IS6110 and their flanking sequences is generated by linker
      mediated PCR. The amplicons are then hybridized to immobilized oligonucleotide
      probes that are specific for known IS6110 insertion sites. The method was
      evaluated using an array of oligonucleotide probes corresponding to IS6110
      insertion sites from M. tuberculosis strains CDC1551, Erdman, and H37Rv, and
      multidrug-resistant strain W. A set of 72 DNA samples from 60 M. tuberculosis
      clinical isolates was analyzed for the presence or absence of these insertion
      sites, and the assay was found to be highly reproducible. This method of
      identifying insertion sites has been named "insite" and can be used for the
      genotyping of M. tuberculosis complex strains based on IS6110 insertion site
      profiles.

PMID- 11230398
TI  - Infection with Bartonella weissii and detection of Nanobacterium antigens in a
      North Carolina beef herd.
AB  - Very recently, Bartonella organisms have been isolated from large ruminants
      (deer, elk, and dairy and beef cattle) located in the United States and in
      France. In this study, we report the serologic, microbiologic, and molecular
      findings related to the isolation of a Bartonella species in North Carolina beef
      cattle and the detection of nanobacterial antigen using a commercially available
      enzyme-linked immunosorbent assay. Between August 1998 and September 1999, blood
      was collected from 38 cattle ranging in age from 1 month to 6.5 years. After a 1
      month incubation period, a Bartonella sp. was isolated on a 5% rabbit blood agar
      plate from three of six EDTA blood samples. PCR amplification of the 16S rRNA
      gene from all three isolates resulted in a DNA sequence that was 100% identical
      to that of B. weissii 16S rRNA (GenBank no. AF199502). By IFA testing, 36 of 38
      cattle had antibodies (> or =1:64) to Bartonella weissii (bovine origin)
      antigens. Nanobacterial antigen was detected in 22 of 22 serum samples. We
      conclude that infection with an organism similar or closely related to B. weissii
      can occur in North Carolina cattle and that although their actual existence is
      still controversial Nanobacterium antigens were detected with a commercially
      available test kit. The epidemiology, vector biology, and potential pathogenicity
      of these organisms in cattle deserve future consideration.

PMID- 11230399
TI  - Genotyping of enterotoxigenic Clostridium perfringens fecal isolates associated
      with antibiotic-associated diarrhea and food poisoning in North America.
AB  - Clostridium perfringens type A isolates producing enterotoxin (CPE) are an
      important cause of food poisoning and non-food-borne human gastrointestinal (GI)
      diseases, including antibiotic-associated diarrhea (AAD). Recent studies suggest
      that C. perfringens type A food poisoning is caused by C. perfringens isolates
      carrying a chromosomal cpe gene, while CPE-associated non-food-borne GI diseases,
      such as AAD, are caused by plasmid cpe isolates. Those putative relationships,
      obtained predominantly with European isolates, were tested in the current study
      by examining 34 cpe-positive, C. perfringens fecal isolates from North American
      cases of food poisoning or AAD. These North American disease isolates were all
      classified as type A using a multiplex PCR assay. Furthermore, restriction
      fragment length polymorphism and pulsed-field gel electrophoresis genotyping
      analyses showed the North American AAD isolates included in this collection all
      have a plasmid cpe gene, but the North American food poisoning isolates all carry
      a chromosomal cpe gene. Western blotting demonstrated CPE expression by nearly
      all of these disease isolates, confirming their virulence potential. These
      findings with North American isolates provide important new evidence that,
      regardless of geographic origin or date of isolation, plasmid cpe isolates cause
      most CPE-associated AAD cases and chromosomal cpe isolates cause most C.
      perfringens type A food poisoning cases. These findings hold importance for the
      development of assays for distinguishing cases of CPE-associated food-borne and
      non-food-borne human GI illnesses and also identify potential epidemiologic tools
      for determining the reservoirs for these illnesses.

PMID- 11230400
TI  - National epidemiologic surveys of Enterobacter aerogenes in Belgian hospitals
      from 1996 to 1998.
AB  - Two national surveys were conducted to describe the incidence and prevalence of
      Enterobacter aerogenes in 21 Belgian hospitals in 1996 and 1997 and to
      characterize the genotypic diversity and the antimicrobial resistance profiles of
      clinical strains of E. aerogenes isolated from hospitalized patients in Belgium
      in 1997 and 1998. Twenty-nine hospitals collected 10 isolates of E. aerogenes,
      which were typed by arbitrarily primed PCR (AP-PCR) using two primers and pulsed
      field gel electrophoresis. MICs of 10 antimicrobial agents were determined by the
      agar dilution method. Beta-lactamases were detected by the double-disk diffusion
      test and characterized by isoelectric point. The median incidence of E. aerogenes
      colonization or infection increased from 3.3 per 1,000 admissions in 1996 to 4.2
      per 1000 admissions in the first half of 1997 (P < 0.01). E. aerogenes strains (n
      = 260) clustered in 25 AP-PCR types. Two major types, BE1 and BE2, included 36
      and 38% of strains and were found in 21 and 25 hospitals, respectively. The BE1
      type was indistinguishable from a previously described epidemic strain in France.
      Half of the strains produced an extended-spectrum beta-lactamase, either TEM-24
      (in 86% of the strains) or TEM-3 (in 14% of the strains). Over 75% of the
      isolates were resistant to ceftazidime, piperacillin-tazobactam, and
      ciprofloxacin. Over 90% of the strains were susceptible to cefepime, carbapenems,
      and aminoglycosides. In conclusion, these data suggest a nationwide dissemination
      of two epidemic multiresistant E. aerogenes strains in Belgian hospitals. TEM-24
      beta-lactamase was frequently harbored by one of these epidemic strains, which
      appeared to be genotypically related to a TEM-24-producing epidemic strain from
      France, suggesting international dissemination.

PMID- 11230401
TI  - Isolation and characterization of polymorphic DNA from Entamoeba histolytica.
AB  - An important gap in our understanding of the epidemiology of amebiasis is what
      determines the outcome of Entamoeba histolytica infections. To investigate the
      possible existence of invasive and noninvasive strains as one factor, the ability
      to differentiate individual isolates of E. histolytica is necessary. Two new loci
      containing internal repeats, locus 1-2 and locus 5-6, have been isolated. Each
      contains a single repeat block with two types of related direct repeats arranged
      in tandem. Southern blot analysis suggests that both loci are multicopy and may
      themselves be arranged in tandem arrays. Three other previously reported,
      internally repetitive loci containing at least two repeat blocks each with one or
      more related repeat units were also investigated. PCR was used to study
      polymorphism at each of these loci, which was detected to various degrees in each
      case. Variation was seen in the total number of bands obtained per isolate and
      their sizes. Nucleotide sequence comparison of loci 1-2 and 5-6 in five axenic
      isolates revealed differences in the number of repeat units, which correlated
      with the observed PCR product size variation, and in repeat sequence. Use of
      multiple loci collectively allowed differentiation of a majority of the 13
      isolates studied, and we believe that these loci have the potential to be used as
      polymorphic molecular markers for investigating the epidemiology of E.
      histolytica and the potential existence of genetically distinct invasive and
      noninvasive strains.

PMID- 11230402
TI  - Enzyme-linked immunosorbent assay using a virus type-specific peptide based on a
      subdomain of envelope protein E(rns) for serologic diagnosis of pestivirus
      infections in swine.
AB  - Peptides deduced from the C-terminal end (residues 191 to 227) of pestivirus
      envelope protein E(rns) were used to develop enzyme-linked immunosorbent assays
      (ELISAs) to measure specifically antibodies against different types of
      pestiviruses. The choice of the peptide was based on the modular structure of the
      E(rns) protein, and the peptide was selected for its probable independent folding
      and good exposure, which would make it a good candidate for an antigenic peptide
      to be used in a diagnostic test. A solid-phase peptide ELISA which was cross
      reactive for several types of pestivirus antibodies and which can be used for the
      general detection of pestivirus antibodies was developed. To identify type
      specific pestivirus antibodies, a liquid-phase peptide ELISA, with a labeled,
      specific classical swine fever virus (CSFV) peptide and an unlabeled bovine viral
      diarrhea virus peptide to block cross-reactivity, was developed. Specificity and
      sensitivity of the liquid-phase peptide ELISA for CSFV were 98 and 100%,
      respectively. Because the peptide is a fragment of the E(rns) protein, it can be
      used to differentiate between infected and vaccinated animals when a vaccine
      based on the E2 protein, which is another pestivirus envelope protein, is used.

PMID- 11230403
TI  - Frequency of acyclovir-resistant herpes simplex virus in clinical specimens and
      laboratory isolates.
AB  - The proportion of acyclovir (ACV)-resistant herpes simplex virus (HSV) isolates
      in clinical specimens and laboratory isolates was determined. HSV isolates in
      clinical specimens and laboratory isolates were cultured in the absence or
      presence of 5 microg of ACV per ml. The frequency of ACV-resistant HSV was
      calculated as (average virus titer in the wells with ACV)/(average virus titer in
      the wells without ACV). The mutation frequency of HSV type 1 isolates in clinical
      samples (directly from patient lesions) was 7.5 x 10(-4) +/- 2.5 x 10(-4) (mean
      +/- standard error), and that of HSV type 2 isolates was 15.0 x 10(-4) +/- 4.6 x
      10(-4). The mutation frequencies of isolates derived in the laboratory from these
      clinical samples were very similar. Similarly, the 50% inhibitory concentrations
      for isolates in clinical samples and laboratory isolates were identical. The
      frequencies of ACV-resistant HSV types 1 and 2 were in a narrow range of 7.5 x
      10(-4) to 15.0 x 10(-4) among isolates in clinical specimens and did not change
      for laboratory-derived pools of viral isolates.

PMID- 11230404
TI  - Comparative pathogenesis of infection of pigs with hepatitis E viruses recovered
      from a pig and a human.
AB  - Specific-pathogen-free pigs were inoculated with one of two hepatitis E viruses
      (HEV) (one recovered from a pig and the other from a human) to study the relative
      pathogenesis of the two viruses in swine. Fifty-four pigs were randomly assigned
      to three groups. Seventeen pigs in group 1 served as uninoculated controls, 18
      pigs in group 2 were intravenously inoculated with the swine HEV recovered from a
      pig in the United States, and 19 pigs in group 3 were intravenously inoculated
      with the US-2 strain of human HEV recovered from a hepatitis patient in the
      United States. Two to four pigs from each group were necropsied at 3, 7, 14, 20,
      27, or 55 days postinoculation (DPI). Evidence of clinical disease or elevation
      of liver enzymes or bilirubin was not found in pigs from any of the three groups.
      Enlarged hepatic and mesenteric lymph nodes were observed in both HEV-inoculated
      groups. Multifocal lymphoplasmacytic hepatitis was observed in 9 of 17, 15 of 18,
      and 16 of 19 pigs in groups 1 to 3, respectively. Focal hepatocellular necrosis
      was observed in 5 of 17, 10 of 18, and 13 of 19 pigs in groups 1 to 3,
      respectively. Hepatitis lesions were very mild in group 1 pigs, mild to moderate
      in group 2 pigs, and moderate to severe in group 3 pigs. Hepatic inflammation and
      hepatocellular necrosis peaked in severity at 20 DPI and were still moderately
      severe at 55 DPI in the group inoculated with human HEV. Hepatitis lesions were
      absent or nearly resolved by 55 DPI in the swine-HEV-inoculated pigs. All HEV
      inoculated pigs seroconverted to anti-HEV immunoglobulin G. HEV RNA was detected
      by reverse transcriptase PCR in feces, liver tissue, and bile of pigs in both HEV
      inoculated groups from 3 to 27 DPI. Based on evaluation of microscopic lesions,
      the US-2 strain of human HEV induced more severe and persistent hepatic lesions
      in pigs than did swine HEV. Pig livers or cells from the livers of HEV-infected
      pigs may represent a risk for transmission of HEV from pigs to human xenograft
      recipients. Since HEV was shed in the feces of infected pigs, exposure to feces
      from infected pigs represents a risk for transmission of HEV, and pigs should be
      considered a reservoir for HEV.

PMID- 11230405
TI  - Genetic organization of Pasteurella multocida cap Loci and development of a
      multiplex capsular PCR typing system.
AB  - Current serotyping methods classify Pasteurella multocida into five capsular
      serogroups (serogroups A, B, D, E, and F) and 16 somatic serotypes (serotypes 1
      to 16). In the present study, we have developed a multiplex PCR assay as a rapid
      alternative to the conventional capsular serotyping system. The serogroup
      specific primers used in this assay were designed following identification,
      sequence determination, and analysis of the capsular biosynthetic loci of each
      capsular serogroup. The entire capsular biosynthetic loci of P. multocida A:1 (X
      73) and B:2 (M1404) have been cloned and sequenced previously (J. Y. Chung, Y. M.
      Zhang, and B. Adler, FEMS Microbiol. Lett. 166:289-296, 1998; J. D. Boyce, J. Y.
      Chung, and B. Adler, Vet. Microbiol. 72:121-134, 2000). Nucleotide sequence
      analysis of the biosynthetic region (region 2) from each of the remaining three
      serogroups, serogroups D, E, and F, identified serogroup-specific regions and
      gave an indication of the capsular polysaccharide composition. The multiplex
      capsular PCR assay was highly specific, and its results, with the exception of
      those for some serogroup F strains, correlated well with conventional serotyping
      results. Sequence analysis of the strains that gave conflicting results confirmed
      the validity of the multiplex PCR and indicated that these strains were in fact
      capsular serogroup A. The multiplex PCR will clarify the distinction between
      closely related serogroups A and F and constitutes a rapid assay for the
      definitive classification of P. multocida capsular types.

PMID- 11230406
TI  - Clinical significance and taxonomy of Actinobacillus hominis.
AB  - Clinical findings in 36 immunosuppressed patients with lower respiratory tract
      infection or bacteremia with Actinobacillus hominis are described. Animal contact
      was only recorded for three patients; nine patients died despite appropriate
      antimicrobial treatment. Although infections with this microorganism seem to be
      rare, the fact that 37 of 46 strains characterized in this study have been found
      in Copenhagen indicates that under-reporting may occur. A. hominis is
      phenotypically relatively homogeneous but can be difficult to differentiate from
      other Actinobacillus species unless extensive biochemical testing is performed.
      Mannose-positive strains of A. hominis are especially difficult to differentiate
      from A. equuli. Attempts to identify A. hominis by automatic identification
      systems may lead to misidentifications. Ribotyping and DNA-DNA hybridization data
      show that A. hominis is a homogeneous species clearly separated from other
      species within the genus Actinobacillus.

PMID- 11230407
TI  - Diagnostics of neisseriaceae and moraxellaceae by ribosomal DNA sequencing:
      ribosomal differentiation of medical microorganisms.
AB  - Fast and reliable identification of microbial isolates is a fundamental goal of
      clinical microbiology. However, in the case of some fastidious gram-negative
      bacterial species, classical phenotype identification based on either metabolic,
      enzymatic, or serological methods is difficult, time-consuming, and/or
      inadequate. 16S or 23S ribosomal DNA (rDNA) bacterial sequencing will most often
      result in accurate speciation of isolates. Therefore, the objective of this study
      was to find a hypervariable rDNA stretch, flanked by strongly conserved regions,
      which is suitable for molecular species identification of members of the
      Neisseriaceae and Moraxellaceae. The inter- and intrageneric relationships were
      investigated using comparative sequence analysis of PCR-amplified partial 16S and
      23S rDNAs from a total of 94 strains. When compared to the type species of the
      genera Acinetobacter, Moraxella, and Neisseria, an average of 30 polymorphic
      positions was observed within the partial 16S rDNA investigated (corresponding to
      Escherichia coli positions 54 to 510) for each species and an average of 11
      polymorphic positions was observed within the 202 nucleotides of the 23S rDNA
      gene (positions 1400 to 1600). Neisseria macacae and Neisseria mucosa subsp.
      mucosa (ATCC 19696) had identical 16S and 23S rDNA sequences. Species clusters
      were heterogeneous in both genes in the case of Acinetobacter lwoffii, Moraxella
      lacunata, and N. mucosa. Neisseria meningitidis isolates failed to cluster only
      in the 23S rDNA subset. Our data showed that the 16S rDNA region is more suitable
      than the partial 23S rDNA for the molecular diagnosis of Neisseriaceae and
      Moraxellaceae and that a reference database should include more than one strain
      of each species. All sequence chromatograms and taxonomic and disease-related
      information are available as part of our ribosomal differentiation of medical
      microorganisms (RIDOM) web-based service (http://www.ridom.hygiene.uni
      wuerzburg.de/). Users can submit a sequence and conduct a similarity search
      against the RIDOM reference database for microbial identification purposes.

PMID- 11230408
TI  - Diversity within reference strains of Corynebacterium matruchotii includes
      Corynebacterium durum and a novel organism.
AB  - Corynebacterium matruchotii has been the subject of numerous dental pathogenesis
      studies. The purpose of the present study was to resolve concerns about diversity
      within the reference strains of C. matruchotii through analysis of seven strains
      procured from the American Type Culture Collection (ATCC). Analysis of whole-cell
      fatty acid profiles with the library generation software of Microbial ID Inc.
      revealed that three types of organisms have been deposited in the ATCC as C.
      matruchotii. These three groups of organisms were also distinguishable by DNA-DNA
      dot blot hybridization, by sequences of two hypervariable regions of the 16S rRNA
      gene, and by the pyrrolidonyl arylamidase test. These studies indicate that two
      C. matruchotii reference strains, ATCC 33449 and ATCC 33822, are members of the
      recently proposed species, Corynebacterium durum. The colonial morphology and
      biochemical reactions of the C. durum strains are more diverse than originally
      reported. Strain ATCC 43833 is unique and represents a novel species. In addition
      to the type strain, ATCC 14266, true members of the species C. matruchotii
      include ATCC strains 14265, 33806, and 43832 plus two reference strains, L2 and
      Richardson 13, which comprise the vast majority of strains used in dental
      pathogenesis research with this species.

PMID- 11230409
TI  - Prevalence and antifungal susceptibility of 442 Candida isolates from blood and
      other normally sterile sites: results of a 2-year (1996 to 1998) multicenter
      surveillance study in Quebec, Canada.
AB  - During a 2-year surveillance program (1996 to 1998) in Quebec, Canada, 442
      strains of Candida species were isolated from 415 patients in 51 hospitals. The
      distribution of species was as follows: Candida albicans, 54%; C. glabrata, 15%;
      C. parapsilosis, 12%; C. tropicalis, 9%; C. lusitaniae, 3%; C. krusei, 3%; and
      Candida spp., 3%. These data, compared to those of a 1985 survey, indicate
      variations in species distribution, with the proportions of C. glabrata and C.
      parapsilosis increasing by 9 and 4%, respectively, and those of C. albicans and
      C. tropicalis decreasing by 10 and 7%, respectively. However, these differences
      are statistically significant for C. glabrata and C. tropicalis only. MICs of
      amphotericin B were > or =4 microg/ml for 3% of isolates, all of which were non
      C. albicans species. Three percent of C. albicans isolates were resistant to
      flucytosine (> or =32 microg/ml). Resistance to itraconazole (> or =1 microg/ml)
      and fluconazole (> or =64 microg/ml) was observed, respectively, in 1 and 1% of
      C. albicans, 14 and 9% of C. glabrata, 5 and 0% of C. tropicalis, and 0% of C.
      parapsilosis and C. lusitaniae isolates. Clinical data were obtained for 343
      patients. The overall crude mortality rate was 38%, reflecting the multiple
      serious underlying illnesses found in these patients. Bloodstream infections were
      documented for 249 patients (73%). Overall, systemic triazoles had been
      administered to 10% of patients before the onset of candidiasis. The frequency of
      isolation of non-C. albicans species was significantly higher in this group of
      patients. Overall, only two C. albicans isolates were found to be resistant to
      fluconazole. These were obtained from an AIDS patient and a leukemia patient,
      both of whom had a history of previous exposure to fluconazole. At present, it
      appears that resistance to fluconazole in Quebec is rare and is restricted to
      patients with prior prolonged azole treatment.

PMID- 11230410
TI  - In vitro fungicidal activities of voriconazole, itraconazole, and amphotericin B
      against opportunistic moniliaceous and dematiaceous fungi.
AB  - The NCCLS proposed standard M38-P describes standard parameters for testing the
      fungistatic antifungal activities (MICs) of established agents against
      filamentous fungi (molds); however, standard conditions are not available for
      testing their fungicidal activities (minimum fungicidal or lethal concentrations
      [MFCs]). This study evaluated the in vitro fungistatic and fungicidal activities
      of voriconazole, itraconazole, and amphotericin B against 260 common and emerging
      molds (174 Aspergillus sp. isolates [five species], 23 Fusarium sp. isolates
      [three species], 6 Paecilomyces lilacinus isolates, 6 Rhizopus arrhizus isolates,
      23 Scedosporium sp. isolates, 23 dematiaceous fungi, and 5 Trichoderma
      longibrachiatum isolates). MICs were determined by following the NCCLS M38-P
      broth microdilution method. MFCs were the lowest drug dilutions that resulted in
      fewer than three colonies. Voriconazole showed similar or better fungicidal
      activity (MFC at which 90% of isolates tested are killed [MFC(90)], 1 to 2
      microg/ml) than the reference agents for Aspergillus spp. with the exception of
      Aspergillus terreus (MFC(90) of voriconazole and amphotericin B, >8 microg/ml).
      The voriconazole geometric mean (G mean) MFC for Scedosporium apiospermum was
      lower (2.52 microg/ml) than those of the other two agents (5.75 to 7.5
      microg/ml). In contrast, amphotericin B and itraconazole G mean MFCs for R.
      arrhizus were 2.1 to 2.2 microg/ml, but that for voriconazole was >8 microg/ml.
      Little or no fungicidal activity was shown for Fusarium spp. (2 to >8 microg/ml)
      and Scedosporium prolificans (>8 microg/ml) by the three agents, but voriconazole
      had some activity against P. lilacinus and T. longibrachiatum (G mean MFCs, 1.8
      and 4 microg/ml, respectively). The fungicidal activity of the three agents was
      similar (G mean MFC, 1.83 to 2.36 microg/ml) for the dematiaceous fungi with the
      exception of the azole MFCs (>8 microg/ml) for some Bipolaris spicifera and
      Dactylaria constricta var. gallopava. These data extend and corroborate the
      available fungicidal results for the three agents. The role of the MFC as a
      predictor of clinical outcome needs to be established in clinical trials by
      following standardized testing conditions for determination of these in vitro
      values.

PMID- 11230411
TI  - Use of immunoglobulin G antibody avidity for differentiation of primary human
      herpesvirus 6 and 7 infections.
AB  - A human herpesvirus 7 (HHV-7) indirect immunofluorescence antibody avidity test
      was developed and used with an existing human herpesvirus 6 (HHV-6) antibody
      avidity test to detect and distinguish low-avidity antibodies to HHV-6 and HHV-7
      and hence the respective primary infections. With sera from 269 British children
      aged 0 to 179 weeks, the tests showed that most (10 of 98 serum samples [13%])
      HHV-6 low-avidity antibody was found in the first year of life, whereas for HHV
      7, most (18 of 101 serum samples [20%]) HHV-7 low-avidity antibody was found in
      the second year of life. Five children had low-avidity antibodies to both
      viruses. Of nine Japanese children with previously serologically proven primary
      HHV-6 or HHV-7 infections, eight had low-avidity antibody only to the relevant
      virus, but one child had low-avidity antibodies to HHV-6 and HHV-7. The avidity
      tests were applied to five British children and further proof of viral infection
      was sought by the detection of specific DNA in serum or plasma, and saliva or
      cerebrospinal fluid. In two children who had low-avidity antibody to HHV-7 but
      who were seronegative for HHV-6, only HHV-7 was found. Both viruses were detected
      in one child with low-avidity HHV-7 antibody and high-avidity HHV-6 antibody. In
      two children with low-avidity antibodies to both viruses, HHV-6 and HHV-7 DNAs
      were found, confirming dual primary infections and excluding antibody cross
      reactivity.

PMID- 11230412
TI  - Application of the Sherlock Mycobacteria Identification System using high
      performance liquid chromatography in a clinical laboratory.
AB  - There is a growing need for a more accurate, rapid, and cost-effective
      alternative to conventional tests for identification of clinical isolates of
      Mycobacterium species. Therefore, the ability of the Sherlock Mycobacteria
      Identification System (SMIS; MIDI, Inc.) using computerized software and a
      Hewlett-Packard series 1100 high-performance liquid chromatograph to identify
      mycobacteria was compared to identification using phenotypic characteristics,
      biochemical tests, probes (Gen-Probe, Inc.), gas-liquid chromatography, and, when
      necessary, PCR-restriction enzyme analysis of the 65-kDa heat shock protein gene
      and 16S rRNA gene sequencing. Culture, harvesting, saponification, extraction,
      derivatization, and chromatography were performed following MIDI's instructions.
      Of 370 isolates and stock cultures tested, 327 (88%) were given species names by
      the SMIS. SMIS software correctly identified 279 of the isolates (75% of the
      total number of isolates and 85% of the named isolates). The overall predictive
      value of accuracy (correct calls divided by total calls of a species) for SMIS
      species identification was 85%, ranging from only 27% (3 of 11) for M. asiaticum
      to 100% for species or groups including M. malmoense (8 of 8), M.
      nonchromogenicum (11 of 11), and the M. chelonae-abscessus complex (21 of 21). By
      determining relative peak height ratios (RPHRs) and relative retention times
      (RRTs) of selected mycolic acid peaks, as well as phenotypic properties, all 48
      SMIS-misidentified isolates and 39 (91%) of the 43 unidentified isolates could be
      correctly identified. Material and labor costs per isolate were $10.94 for SMIS,
      $26.58 for probes, and $42.31 for biochemical identification. The SMIS, combined
      with knowledge of RPHRs, RRTs, and phenotypic characteristics, offers a rapid,
      reasonably accurate, cost-effective alternative to more traditional methods of
      mycobacterial species identification.

PMID- 11230413
TI  - Identification of enteropathogenic Escherichia coli in simian immunodeficiency
      virus-infected infant and adult rhesus macaques.
AB  - Enteropathogenic Escherichia coli (EPEC) was recognized as a common opportunistic
      pathogen of simian immunodeficiency virus-infected rhesus macaques (Macaca
      mulatta) with AIDS. Retrospective analysis revealed that 27 of 96 (28.1%) animals
      with AIDS had features of EPEC infection, and EPEC was the most frequent pathogen
      of the gastrointestinal tract identified morphologically. In 7.3% of animals
      dying with AIDS, EPEC represented the sole opportunistic agent of the
      gastrointestinal tract at death. In 20.8% of cases, it was seen in combination
      with one or more gastrointestinal pathogens, including Cryptosporidium parvum,
      Enterocytozoon bieneusi, Mycobacterium avium, Entamoeba histolytica, Balantidium
      coli, Strongyloides stercoralis, cytomegalovirus, and adenovirus. Clinically,
      infection was associated with persistent diarrhea and wasting and was more
      frequent in animals that died at under 1 year of age (P < 0.001, Fisher exact
      test). The organism was associated with the characteristic attaching and effacing
      lesion in colonic tissue sections and produced a focal adherence pattern on a HEp
      2 assay but was negative for Shiga toxin production as assessed by PCR and a HeLa
      cell cytotoxicity assay. A 2.6-kb fragment encompassing the intimin gene was
      amplified and sequenced and revealed 99.2% identity to sequences obtained from
      human isolates (GenBank AF116899) corresponding to the epsilon intimin subtype.
      Further investigations with rhesus macaques may offer opportunities to study the
      impact of EPEC on AIDS pathogenesis and gastrointestinal dysfunction.

PMID- 11230414
TI  - Identification of B-cell epitope of dengue virus type 1 and its application in
      diagnosis of patients.
AB  - Using a serotype-specific monoclonal antibody (MAb) of dengue virus type 1 (DEN
      1), 15F3-1, we identified the B-cell epitope of DEN-1 from a random peptide
      library displayed on phage. Fourteen immunopositive phage clones that bound
      specifically to MAb 15F3-1 were selected. These phage-borne peptides had a
      consensus motif of HxYaWb (a = S/T, b = K/H/R) that mimicked the sequence HKYSWK,
      which corresponded to amino acid residues 111 to 116 of the nonstructural protein
      1 (NS1) of DEN-1. Among the four synthetic peptides corresponding to amino acid
      residues 110 to 117 of the NS1 of DEN-1, -2, -3, and -4, only one peptide,
      EHKYSWKS (P14M) of DEN-1, was found to bind to 15F3-1 specifically. Furthermore,
      P14M was shown to inhibit the binding of phage particles to 15F3-1 in a
      competitive inhibition assay. Histidine(111) (His(111)) was crucial to the
      binding of P14M to 15F3-1, since its binding activity dramatically reduced when
      it changed to leucine(111) (Leu(111)). This epitope-based peptide demonstrated
      its clinical diagnostic potential when it reacted with a high degree of
      specificity with serum samples obtained from both DEN-1-infected rabbits and
      patients. Based on these observations, our DEN-1 epitope-based serologic test
      could be useful in laboratory viral diagnosis and in understanding the
      pathogenesis of DEN-1.

PMID- 11230415
TI  - Controlled clinical comparison of BACTEC plus anaerobic/F to standard anaerobic/F
      as the anaerobic companion bottle to plus aerobic/F medium for culturing blood
      from adults.
AB  - To determine the optimal anaerobic companion bottle to pair with BACTEC Plus
      Aerobic/F medium for recovery of pathogenic microorganisms from adult patients
      with bacteremia and fungemia, we compared Plus Anaerobic/F bottles with Standard
      Anaerobic/F bottles, each of which was filled with 4 to 6 ml of blood. The two
      bottles were paired with a Plus Aerobic/F bottle filled with 8 to 12 ml of blood.
      A total of 14,011 blood culture sets were obtained. Of these, 11,583 sets were
      received with all three bottles filled adequately and 12,257 were received with
      both anaerobic bottles filled adequately. Of 818 clinically important isolates
      detected in one or both adequately filled anaerobic bottles, significantly more
      staphylococci (P < 0.001), streptococci (P < 0.005), Escherichia coli isolates (P
      < 0.02), Klebsiella pneumoniae isolates (P < 0.005), and all microorganisms
      combined (P < 0.001) were detected in Plus Anaerobic/F bottles. In contrast,
      significantly more anaerobic gram-negative bacilli were detected in Standard
      Anaerobic/F bottles (P < 0.05). Of 397 unimicrobial episodes of septicemia, 354
      were detected with both pairs, 30 were detected with Plus Aerobic/F-Plus
      Anaerobic/F pairs only, and 13 were detected with Plus Aerobic/F-Standard
      Anaerobic/F pairs only (P < 0.05). Significantly more episodes of bacteremia
      caused by members of the family Enterobacteriaceae (P < 0.05) and aerobic and
      facultative gram-positive bacteria (P < 0.025) were detected with Plus
      Anaerobic/F bottles only. In a paired-bottle analysis, 810 of 950 isolates were
      recovered from both pairs, 90 were recovered from Plus Aerobic/F-Plus Anaerobic/F
      pairs only, and 50 were recovered from Plus Aerobic/F-Standard Anaerobic/F pairs
      only (P < 0.001). Paired Plus Aerobic/F-Plus Anaerobic/F bottles yielded
      significantly more staphylococci (P < 0.001), streptococci (P < 0.05), and
      members of the family Enterobacteriaceae (P <0.001). We conclude that Plus
      Anaerobic/F bottles detect more microorganisms and episodes of bacteremia and
      fungemia than Standard Anaerobic/F bottles as companion bottles to Plus Aerobic/F
      bottles in the BACTEC 9240 blood culture system.

PMID- 11230416
TI  - Outbreak of subclinical mastitis in a flock of dairy sheep associated with
      Burkholderia cepacia complex infection.
AB  - An outbreak of subclinical mastitis in a flock of 620 milking sheep was
      investigated. Microbiological and epidemiological analyses identified the
      causative agent as belonging to the Burkholderia cepacia complex (formerly
      Pseudomonas cepacia). Every ewe in the milking flock was individually tested for
      subclinical mastitis on two separate occasions, 6 weeks apart, by the California
      (rapid) mastitis test (CMT). The proportion of CMT-positive ewes was 69 of 393
      (17.6%) on the first sampling and 27 of 490 (5.5%) on the second sampling. Pure
      B. cepacia cultures identified with the API 20 NE system were grown from 64 of 96
      (66.7%) CMT-positive ewes and from 1 of 33 (3.0%) CMT-negative ewes. Statistical
      analysis confirmed the significant association between a positive CMT result and
      a positive culture result for B. cepacia complex. Additional polyphasic taxonomic
      analyses of eight isolates showed that seven belonged to B. cepacia genomovar
      III; the remaining isolate was identified as Burkholderia vietnamiensis (formerly
      B. cepacia genomovar V). Bacteriological investigation of samples from milking
      equipment and other environmental sites failed to identify "B. cepacia" in any of
      the samples taken. To our knowledge, this is the first report of an outbreak of
      natural infection in animals caused by B. cepacia complex and the first
      description of B. cepacia complex infection in sheep.

PMID- 11230417
TI  - Mannosidase production by viridans group streptococci.
AB  - The production of mannosidase activity by all currently recognized species of
      human viridans group streptococci was determined using an assay in which
      bacterial growth was dependent on the degradation of the high-mannose-type
      glycans of RNase B and subsequent utilization of released mannose. RNase B is an
      excellent substrate for the demonstration of mannosidase activity since it is a
      glycoprotein with a single glycosylation site which is occupied by high-mannose
      type glycoforms containing five to nine mannose residues. Mannosidase activity
      was produced only by some members of the mitis group (Streptococcus mitis,
      Streptococcus oralis, Streptococcus gordonii, Streptococcus cristatus,
      Streptococcus infantis, Streptococcus parasanguinis, and Streptococcus
      pneumoniae) and Streptococcus intermedius of the anginosus group. None of the
      other species within the salivarius and mutans groups or Streptococcus peroris
      and Streptococcus sanguinis produced mannosidase activity. Using matrix-assisted
      laser desorption ionization time-of-flight mass spectrometry, it was demonstrated
      that the Man(5) glycan alone was degraded while Man(6) to Man(9), which contain
      terminal alpha(1-->2) mannose residues in addition to the alpha(1-->3), alpha(1-
      >6), and beta(1-->4) residues present in Man(5), remained intact. Investigations
      on mannosidase production using synthetic (4-methylumbelliferone- or p
      nitrophenol-linked) alpha- or beta-mannosides as substrates indicated that there
      was no correlation between degradation of these substrates and degradation of the
      Man(5) glycan of RNase B. No species degraded these alpha-linked mannosides,
      while degradation of the beta-linked synthetic substrates was restricted to
      strains within the Streptococcus anginosus, S. gordonii, and S. intermedius
      species. The data generated using a native glycoprotein as the substrate
      demonstrate that mannosidase production within the viridans group streptococci is
      more widely distributed than had previously been considered.

PMID- 11230418
TI  - Serology of typhoid fever in an area of endemicity and its relevance to
      diagnosis.
AB  - Currently, the laboratory diagnosis of typhoid fever is dependent upon either the
      isolation of Salmonella enterica subsp. enterica serotype Typhi from a clinical
      sample or the detection of raised titers of agglutinating serum antibodies
      against the lipopolysaccharide (LPS) (O) or flagellum (H) antigens of serotype
      Typhi (the Widal test). In this study, the serum antibody responses to the LPS
      and flagellum antigens of serotype Typhi were investigated with individuals from
      a region of Vietnam in which typhoid is endemic, and their usefulness for the
      diagnosis of typhoid fever was evaluated. The antibody responses to both antigens
      were highly variable among individuals infected with serotype Typhi, and elevated
      antibody titers were also detected in a high proportion of serum samples from
      healthy subjects from the community. In-house enzyme-linked immunosorbent assays
      (ELISAs) for the detection of specific classes of anti-LPS and antiflagellum
      antibodies were compared with other serologically based tests for the diagnosis
      of typhoid fever (Widal TO and TH, anti-serotype Typhi immunoglobulin M [IgM]
      dipstick, and IDeaL TUBEX). At a specificity of > or =0.93, the sensitivities of
      the different tests were 0.75, 0.55, and 0.52 for the anti-LPS IgM, IgG, and IgA
      ELISAs, respectively; 0.28 for the antiflagellum IgG ELISA; 0.47 and 0.32 for the
      Widal TO and TH tests, respectively; and 0.77 for the anti-serotype Typhi IgM
      dipstick assay. The specificity of the IDeaL TUBEX was below 0.90 (sensitivity,
      0.87; specificity, 0.76). The serological assays based on the detection of IgM
      antibodies against either serotype Typhi LPS (ELISA) or whole bacteria (dipstick)
      had a significantly higher sensitivity than the Widal TO test when used with a
      single acute-phase serum sample (P < or = 0.007). These tests could be of use for
      the diagnosis of typhoid fever in patients who have clinical typhoid fever but
      are culture negative or in regions where bacterial culturing facilities are not
      available.

PMID- 11230419
TI  - Multicenter evaluation of the BDProbeTec ET System for detection of Chlamydia
      trachomatis and Neisseria gonorrhoeae in urine specimens, female endocervical
      swabs, and male urethral swabs.
AB  - The performance of the Becton Dickinson BDProbe Tec ET System Chlamydia
      trachomatis and Neisseria gonorrhoeae Amplified DNA Assays (BD Biosciences,
      Sparks, Md.) was evaluated in a multicenter study. Specimens were collected from
      2,109 men and women, with or without symptoms, attending sexually transmitted
      disease, family planning, and obstetrics and gynecology clinics. Both swab and
      urine samples were collected, and the results obtained from 4,131 specimens were
      compared to those from culture and the LCx nucleic acid amplification test
      (Abbott Industries, Abbott Park, Ill.). PCR and cytospin of the culture transport
      medium with chlamydia direct fluorescent antibody staining were used to
      adjudicate chlamydia culture-negative results. Sensitivity and specificity were
      calculated both with and without use of the amplification control (AC), with
      little apparent difference in the results. Without the AC result, sensitivity for
      C. trachomatis and N. gonorrhoeae were 92.8 and 96.6%, respectively, for cervical
      swabs and 80.5 and 84.9% for urine from women. C. trachomatis and N. gonorrhoeae
      sensitivities were 92.5 and 98.5%, respectively, for male urethral swabs and 93.1
      and 97.9% for urine from men. This amplified DNA system for simultaneous
      detection of chlamydial and gonococcal infections demonstrated superior
      sensitivity compared to chlamydia culture and has performance characteristics
      comparable to those of other commercially available nucleic acid-based assays for
      these organisms.

PMID- 11230421
TI  - Evaluation of a medium (STGG) for transport and optimal recovery of Streptococcus
      pneumoniae from nasopharyngeal secretions collected during field studies.
AB  - Field studies of Streptococcus pneumoniae (pneumococci) nasopharyngeal (NP)
      colonization are hampered by the need to directly plate specimens in order to
      ensure isolate viability. A medium containing skim milk, tryptone, glucose, and
      glycerin (STGG) has been used to transport and store NP material, but its ability
      to preserve pneumococci has not been evaluated. Our objective was to
      qualitatively and semiquantitatively evaluate the ability of STGG to preserve
      pneumococci in NP secretions. Entwined duplicate calcium alginate NP swab samples
      were obtained from children. One swab was plated directly onto a gentamicin blood
      agar plate; the other was placed in STGG. Growth from the directly plated
      specimen was compared with growth from an STGG aliquot immediately cultured or
      stored at -70 degrees C for 9 weeks, -20 degrees C for 9 weeks, or 4 degrees C
      for 5 days. Of 186 specimens, 96 (52%) were positive for pneumococci from the
      direct plating; 94 (98%) of these were positive from the fresh STGG specimen.
      Pneumococci were recovered from all 38 positive specimens frozen at -70 degrees
      C, all 18 positive specimens frozen at -20 degrees C, and 18 of 20 positive
      specimens stored at 4 degrees C. Recovery of pneumococci after storage of NP
      material in STGG medium at -70 degrees C is at least as good as that from direct
      plating. Storage at -20 degrees C is also acceptable. Storage at 4 degrees C for
      5 days is not ideal.

PMID- 11230420
TI  - Evaluation of United States-licensed human immunodeficiency virus immunoassays
      for detection of group M viral variants.
AB  - Six Food and Drug Administration (FDA)-licensed human immunodeficiency virus type
      1 (HIV-1) and HIV-1/2 immunoassays, including five enzyme immunoassays and one
      rapid test, were challenged with up to 250 serum samples collected from various
      global sites. The serum samples were from individuals known to be infected with
      variants of HIV-1 including group M subtypes A, B, B', C, D, E, F, and G and
      group O. All immunoassays detected the vast majority of samples tested. Three
      samples produced low signal over cutoff values in one or more tests: a clade B
      sample, an untypeable sample with a low antibody titer, and a group O sample. It
      is concluded that HIV-1 immunoassays used in the United States are capable of
      detecting most HIV-1 group M variants.

PMID- 11230422
TI  - Persistent ICT malaria P.f/P.v panmalarial and HRP2 antigen reactivity after
      treatment of Plasmodium falciparum malaria is associated with gametocytemia and
      results in false-positive diagnoses of Plasmodium vivax in convalescence.
AB  - A problem with rapid Plasmodium falciparum-specific antigen histidine-rich
      protein 2 (HRP2) detection tests for malaria is the persistence of antigen in
      blood after the disappearance of asexual-stage parasitemia and clinical symptoms,
      resulting in false-positive (FP) test results following treatment. The ICT
      P.f/P.v immunochromatographic test detects both HRP2 and a panmalarial antigen
      (PMA) found in both P. falciparum and Plasmodium vivax. To examine posttreatment
      antigen persistence with this test and whether persistent sexual-stage forms
      (gametocytes) are a cause of FP tests after treatment, we compared serial antigen
      test results with microscopy results from patients symptomatic with P. falciparum
      malaria in Indonesia for 28 days following treatment with chloroquine (CQ; n =
      66), sulfadoxine-pyrimethamine (SP; n = 36), and artesunate plus sulfadoxine
      pyrimethamine (ART + SP; n = 15). Persistent FP antigenemia following SP
      treatment occurred in 29% (HRP2) and 42% (PMA) of the patients on day 7 and in
      10% (HRP2) and 23% (PMA) on day 14. The high rates of persistent HRP2 and PMA
      antigenemia following CQ and SP treatment were strongly associated with the
      presence of gametocytemia, with the proportion with gametocytes on day 7
      posttreatment being significantly greater in those with FP results than in those
      with true-negative PMA and HRP2 results. Gametocyte frequency on day 14 post-SP
      treatment was also greater in those with FP PMA results. Following SP treatment,
      PMA persisted longer than HRP2, giving an FP diagnosis of P. vivax in up to 16%
      of patients on day 14, with all FP P. vivax diagnoses having gametocytemia. In
      contrast, PMA was rapidly cleared following ART + SP treatment in association
      with rapid clearance of gametocytemia. Gametocytes appear to be an important
      cause of persistent posttreatment panmalarial antigenemia in areas of endemicity
      and may also contribute in part to persistent HRP2 antigenemia following
      treatment.

PMID- 11230423
TI  - Evaluation of a fluorescence in situ hybridization assay for differentiation
      between tuberculous and nontuberculous Mycobacterium species in smears of
      Lowenstein-Jensen and Mycobacteria Growth Indicator Tube cultures using peptide
      nucleic acid probes.
AB  - A new fluorescence in situ hybridization assay based on peptide nucleic acid
      probes (MTB and NTM probes targeting tuberculous and nontuberculous species,
      respectively) for the identification of Mycobacterium tuberculosis complex and
      differentiation between tuberculous and nontuberculous mycobacteria (NTM) was
      evaluated using Lowenstein-Jensen (LJ) solid cultures from 100 consecutive sputum
      samples and 50 acid-fast bacillus (AFB)-positive sputum samples as well as
      Mycobacteria Growth Indicator Tube (MGIT) liquid cultures from 80 AFB-positive
      sputum samples. Mycobacterium species could be identified from a total of 53 LJ
      cultures and 77 MGIT cultures. The diagnostic specificities of the MTB and NTM
      probes were 100% for both cultures. The diagnostic sensitivities of the MTB probe
      for the LJ and MGIT cultures were 98 and 99%, respectively, whereas the
      sensitivities of the NTM probe were 57 and 100%, respectively. The relatively low
      sensitivity of the NTM probe was due to a high proportion of M. fortuitum, which
      is not identified by the probe.

PMID- 11230424
TI  - Identification of canine coronavirus strains from feces by S gene nested PCR and
      molecular characterization of a new Australian isolate.
AB  - A nested PCR (nPCR) assay for the detection of canine coronavirus (CCV) in fecal
      samples is described. The target sequence for the assay was a 514-bp fragment
      within the spike (S) glycoprotein gene. The sensitivity of the assay is extremely
      high, detecting as little as 25 50% tissue culture infective doses per g of
      unprocessed feces. A clinical trial using dogs challenged orally with CCV SA4 and
      CCV NVSL was used to compare viral isolation and the nPCR assay as detection
      techniques over a 2-week period of infection. Virus isolation detected CCV
      shedding from day 4 to 9 postchallenge, while the nPCR assay detected CCV
      shedding from day 4 to 13 postchallenge. Cloning and sequencing of the nPCR assay
      product enabled investigation of the evolutionary relationships between strains
      within the S gene. The simple and rapid procedure described here makes this assay
      an ideal alternative technique to electron microscopy and viral isolation in cell
      culture for detection of CCV shedding in feces. The described assay also provides
      a method of identifying new strains of CCV without the complicated and time
      consuming practice of raising antibodies to individual strains. This is
      illustrated by the identification, for the first time, of an Australian isolate
      of CCV (UWSMN-1).

PMID- 11230425
TI  - Molecular and conventional epidemiology of Mycobacterium tuberculosis in
      Botswana: a population-based prospective study of 301 pulmonary tuberculosis
      patients.
AB  - Little is known about patterns of tuberculosis (TB) transmission among
      populations in developing countries with high rates of TB and human
      immunodeficiency virus (HIV) infection. To examine patterns of TB transmission in
      such a setting, we performed a population-based DNA fingerprinting study among TB
      patients in Botswana. Between January 1997 and July 1998, TB patients from four
      communities in Botswana were interviewed and offered HIV testing. Their
      Mycobacterium tuberculosis isolates underwent DNA fingerprinting using IS6110
      restriction fragment length polymorphism, and those with matching fingerprints
      were reinterviewed. DNA fingerprints with >5 bands were considered clustered if
      they were either identical or differed by at most one band, while DNA
      fingerprints with < or =5 bands were considered clustered only if they were
      identical. TB isolates of 125 (42%) of the 301 patients with completed interviews
      and DNA fingerprints fell into 20 different clusters of 2 to 16 patients. HIV
      status was not associated with clustering. Prior imprisonment was the only
      statistically significant risk factor for clustering (risk ratio, 1.5; 95%
      confidence interval, 1.1 to 2.0). In three communities where the majority of
      eligible patients were enrolled, 26 (11%) of 243 patients overall and 26 (25%) of
      104 clustered patients shared both a DNA fingerprint and strong antecedent
      epidemiologic link. Most of the increasing TB burden in Botswana may be
      attributable to reactivation of latent infection, but steps should be taken to
      control ongoing transmission in congregate settings. DNA fingerprinting helps
      determine loci of TB transmission in the community.

PMID- 11230426
TI  - Molecular epidemiology of a Shigella flexneri outbreak in a mountainous township
      in Taiwan, Republic of China.
AB  - An outbreak of shigellosis occurred in a township of Nantou Conuty in central
      Taiwan from August to October in 1996. The infections extended to two neighboring
      townships and continued to the end of 1996. Forty cases were confirmed during the
      period, in contrast to only one confirmed case in Nantou County in 1996 before
      the outbreak. All of these 41 cases in 1996 were identified as infections with
      Shigella flexneri serotype 2a. In order to trace the source of the infections,
      the 41 isolates recovered were analyzed by plasmid profile and pulsed-field gel
      electrophoresis (PFGE). There was no correlation between the plasmid profile
      results and the PFGE results, and the latter were used for subtyping of the 41
      isolates. Twenty-two isolates (53%) had the same NotI and XbaI PFGE patterns, and
      4 isolates (10%) had an additional unstable plasmid band in their NotI patterns
      but otherwise had the same NotI and XbaI patterns as the 22 isolates. These 26
      isolates were designated the outbreak strain, and of these, 24 appeared in eight
      villages in one township and 2 appeared in a neighboring township. Fourteen of
      the remaining 15 isolates, including the isolate recovered 7 months before the
      outbreak, had both NotI and XbaI PFGE patterns closely related to those of the
      outbreak strain, indicating that Shigella infections were endemic in the area. By
      tracing the first isolation dates of the outbreak strain in individual villages
      and the neighboring township, it was found that the strain spread along the major
      arterial road and its branch road as time passed. Our molecular typing results
      and epidemiological data demonstrated the endemic nature of the outbreak strain
      as well as a person-to-person mode of transmission for the widespread infections
      the strain caused.

PMID- 11230427
TI  - Molecular typing and epidemiological study of Salmonella enterica serotype
      Typhimurium isolates from cattle by fluorescent amplified-fragment length
      polymorphism fingerprinting and pulsed-field gel electrophoresis.
AB  - One hundred twenty Salmonella enterica serotype Typhimurium strains, including
      103 isolates from cattle gathered between 1977 and 1999 in the prefecture located
      on the northern-most island of Japan, were analyzed by using fluorescent
      amplified-fragment length polymorphism (FAFLP) and pulsed-field gel
      electrophoresis (PFGE) to examine the genotypic basis of the epidemic. Among
      these strains, there were 17 FAFLP profiles that formed four distinct clusters
      (A, B, C, and D). Isolates that belonged to cluster A have become increasingly
      common since 1992 with the increase of bovine salmonellosis caused by serotype
      Typhimurium. PFGE resolved 25 banding patterns that formed three distinct
      clusters (I, II, and III). All the isolates that belonged to FAFLP cluster A, in
      which all the strains of definitive phage type 104 examined were included, were
      grouped into PFGE cluster I. Taken together, these results indicate that clonal
      exchange of serotype Typhimurium has taken place since 1992, and they show a
      remarkable degree of homogeneity at a molecular level among contemporary isolates
      from cattle in this region. Moreover, we have sequenced two kinds of FAFLP
      markers, 142-bp and 132-bp fragments, which were identified as a polymorphic
      marker of strains that belonged to clusters A and C, respectively. The sequence
      of the 142-bp fragment shows homology with a segment of P22 phage, and that of
      the 132-bp fragment shows homology with a segment of traG, which is an F plasmid
      conjugation gene. FAFLP is apparently as well suited for epidemiological typing
      of serotype Typhimurium as is PFGE, and FAFLP can provide a source of molecular
      markers useful for studies of genetic variation in natural populations of
      serotype Typhimurium.

PMID- 11230428
TI  - Sequence analysis of the direct repeat region in Mycobacterium bovis.
AB  - Spoligotyping is a major tool for molecular typing of Mycobacterium bovis. This
      technique is based on the polymorphism of spacers that separate direct repeats
      (DRs) in the M. tuberculosis complex DR region. Numerous M. bovis strains show a
      lack of several spacers which appears as a gap in the spoligotyping pattern. To
      determine whether these gaps contain alternative spacers not included in the
      spoligotyping membrane, PCRs using primers that hybridize to the spacers adjacent
      to the gaps were performed. Comparing the sizes of products obtained by PCR with
      those deduced from spoligotyping patterns, fragments were selected and sequenced
      to look for alternative spacers. Upon analysis of the sequences, five alternative
      spacers were detected, although deletions of spacers are mainly responsible for
      the observed gaps. The alternative spacers, which are more frequent in M. bovis
      than in M. tuberculosis, may contribute to increased M. bovis differentiation.

PMID- 11230429
TI  - Phenotypic methods for determining genomovar status of the Burkholderia cepacia
      complex.
AB  - Recent taxonomic advances have demonstrated that Burkholderia cepacia is a
      cluster of at least seven closely related genomic species (or genomovars)
      collectively referred to as the B. cepacia complex, all of which may cause
      infections among cystic fibrosis patients and other vulnerable individuals. Thus,
      it is important for clinical microbiologists to be able to differentiate
      genomovars. Prior to this study, 361 B. cepacia complex isolates and 51 isolates
      easily confused with B. cepacia complex previously had been identified using a
      polyphasic approach, and in this study, a comparison of phenotypic and
      biochemical tests was carried out. It was determined that Burkholderia
      multivorans and Burkholderia stabilis could reliably be separated from other
      members of the B. cepacia complex by phenotypic methods. A combination of
      phenotypic and molecular tests such as recA PCR and 16S rRNA RFLP are recommended
      for differentiation among the genomovars of the B. cepacia complex. A biochemical
      reaction scheme for the identification of B. gladioli, Pandoraea species, and
      Ralstonia pickettii and the differentiation of these species from the B. cepacia
      complex is also presented.

PMID- 11230430
TI  - Performance assessment of new multiplex probe assay for identification of
      mycobacteria.
AB  - A new DNA probe assay (INNO LiPA Mycobacteria; Innogenetics, Ghent, Belgium) for
      the simultaneous identification, by means of reverse hybridization and line-probe
      technology, of Mycobacterium tuberculosis complex, Mycobacterium kansasii,
      Mycobacterium xenopi, Mycobacterium gordonae, the species of the Mycobacterium
      avium complex (MAC), Mycobacterium scrofulaceum, and Mycobacterium chelonae was
      evaluated on a panel of 238 strains including, besides representatives of all the
      taxa identifiable by the system, a number of other mycobacteria, some of which
      are known to be problematic with the only other commercial DNA probe system
      (AccuProbe; Gen-Probe, San Diego, Calif.), and two nocardiae. The new kit, which
      includes a control probe reacting with the whole genus Mycobacterium, correctly
      identified 99.6% of the strains tested; the one discrepancy, which remained
      unresolved, concerned an isolate identified as MAC intermediate by INNO LiPA
      Mycobacteria and as Mycobacterium intracellulare by AccuProbe. In five cases,
      because of an imperfect checking of hybridization temperature, a very slight,
      nonspecific, line was visible which was no longer evident when the test was
      repeated. Two strains whose DNA failed amplification at the first attempt were
      regularly identified when the test was repeated. Interestingly, the novel kit
      dodged all the pitfalls presented by the strains giving anomalous reactions with
      AccuProbe. A unique feature of INNO LiPA Mycobacteria is its ability to recognize
      different subgroups within the species M. kansasii and M. chelonae, while the
      declared overlapping reactivity of probe 4 with some M. kansasii and
      Mycobacterium gastri organisms and of probe 9 with MAC, Mycobacterium
      haemophilum, and Mycobacterium malmoense, may furnish a useful aid for their
      identification. The turnaround time of the method is approximately 6 h, including
      a preliminary PCR amplification.

PMID- 11230431
TI  - Epidemiological patterns of rotaviruses causing severe gastroenteritis in young
      children throughout Australia from 1993 to 1996.
AB  - Rotavirus strains that caused severe diarrhea in 4,634 (2,533 male) children aged
      less than 5 years and admitted to major hospitals in eight centers throughout
      Australia from 1993 to 1996 were subject to antigenic and genetic analyses. The G
      serotypes of rotaviruses were identified in 81.9% (3,793 of 4,634) children. They
      included 67.8% (from 3,143 children) serotype G1 isolates (containing 46
      electropherotypes), 11.5% (from 531 children) serotype G2 isolates (27
      electropherotypes), 0.8% (from 39 children) serotype G3 isolates (8
      electropherotypes), and 1.6% (from 76 children) serotype G4 isolates (9
      electropherotypes). G6 (two strains) and G8 (two strains) isolates were
      identified during the same period. G1 serotypes were predominant in all centers,
      with intermittent epidemics of G2 serotypes and sporadic detection of G3 and G4
      strains. With the exception of two strains (typed as G1P2A[6] and G2P2A[6]) all
      serotype G1, G3, and G4 strains were P1A[8] and all serotype G2 strains were
      P1B[4]. Two contrasting epidemiological patterns were identified. In all
      temperate climates rotavirus incidence peaked during the colder months. The
      genetic complexity of strains (as judged by electropherotype) was greatest in
      centers with large populations. Identical electropherotypes appeared each winter
      in more than one center, apparently indicating the spread of some strains both
      from west to east and from east to west. Centers caring for children in small
      aboriginal communities showed unpredictable rotavirus peaks unrelated to climate,
      with widespread dissemination of a few rotavirus strains over distances of more
      than 1,000 km. Data from continued comprehensive etiological studies of genetic
      and antigenic variations in rotaviruses that cause severe disease in young
      children will serve as baseline data for the study of the effect of vaccination
      on the incidence of severe rotavirus disease and on the emergence of new strains.

PMID- 11230432
TI  - Identification of a contaminating Mycobacterium tuberculosis strain with a
      transposition of an IS6110 insertion element resulting in an altered spoligotype.
AB  - Molecular fingerprinting with the IS6110 insertion sequence is useful for
      tracking transmission of Mycobacterium tuberculosis within a population or
      confirming specimen contamination in the laboratory or through instrumentation.
      Secondary typing with other molecular methods yields additional information as to
      the relatedness of strains with similar IS6110 fingerprints. Isolated, relatively
      rare, random events within the M. tuberculosis genome alter molecular
      fingerprinting patterns with any of the methods; therefore, strains which are
      different by two or more typing methods are usually not considered to be closely
      related. In this report, we describe two strains of M. tuberculosis, obtained
      from the same bronchoscope 2 days apart, that demonstrated unique molecular
      fingerprinting patterns by two different typing methods. They were closely linked
      through the bronchoscope by a traditional epidemiologic investigation. Genetic
      analysis of the two strains revealed that a single event, the transposition of an
      IS6110 insertion sequence in one of the strains, accounted for both the
      differences in the IS6110 pattern and the apparent deletion of a spacer in the
      spoligotype. This finding shows that a single event can change the molecular
      fingerprint of a strain in two different molecular typing systems, and thus,
      molecular typing cannot be the only means used to track transmission of this
      organism through a population. Traditional epidemiologic techniques are a
      necessary complement to molecular fingerprinting so that radical changes within
      the fingerprint pattern can be identified.

PMID- 11230433
TI  - Antimicrobial resistance and bacterial identification utilizing a microelectronic
      chip array.
AB  - Species-specific bacterial identification of clinical specimens is often limited
      to a few species due to the difficulty of performing multiplex reactions. In
      addition, discrimination of amplicons is time-consuming and laborious, consisting
      of gel electrophoresis, probe hybridization, or sequencing technology. In order
      to simplify the process of bacterial identification, we combined anchored in situ
      amplification on a microelectronic chip array with discrimination and detection
      on the same platform. Here, we describe the simultaneous amplification and
      discrimination of six gene sequences which are representative of different
      bacterial identification assays: Escherichia coli gyrA, Salmonella gyrA,
      Campylobacter gyrA, E. coli parC, Staphylococcus mecA, and Chlamydia cryptic
      plasmid. The assay can detect both plasmid and transposon genes and can also
      discriminate strains carrying antibiotic resistance single-nucleotide
      polymorphism mutations. Finally, the assay is similarly capable of discriminating
      between bacterial species through reporter-specific discrimination and allele
      specific amplification. Anchored strand displacement amplification allows
      multiplex amplification and complex genotype discrimination on the same platform.
      This assay simplifies the bacterial identification process greatly, allowing
      molecular biology techniques to be performed with minimal processing of samples
      and practical experience.

PMID- 11230435
TI  - Isolation and characterization of a black-pigmented Corynebacterium sp. from a
      woman with spontaneous abortion.
AB  - An unusual black-pigmented coryneform bacterium was isolated from the urogenital
      tract of a woman who experienced a spontaneous abortion during month 6 of
      pregnancy. Biochemical and chemotaxonomic analyses demonstrated that the unknown
      bacterium belonged to the genus Corynebacterium. Phylogenetic analysis based on
      16S rRNA sequences (GenBank accession no. AF220220) revealed that the organism
      was a member of a distinct subline which includes uncultured Corynebacterium
      MTcory 1P (GenBank accession no. AF115934), derived from prostatic fluid, and
      Corynebacterium CDC B8037 (GenBank accession no. AF033314), an uncharacterized
      black-pigmented coryneform bacterium. On the basis of chemotaxonomic and
      phylogenetic evidence, this organism probably represents a new species and is
      most closely related to the uncharacterized Centers for Disease Control and
      Prevention group 4 coryneforms. Our strain is designated CN-1 (ATCC 700975).

PMID- 11230434
TI  - In vitro culture, ultrastructure, antigenic, and molecular characterization of
      Encephalitozoon cuniculi isolated from urine and sputum samples from a Spanish
      patient with AIDS.
AB  - In this report we describe the cultivation of two isolates of microsporidia, one
      from urine and the other from sputum samples from a Spanish AIDS patient. We
      identified them as Encephalitozoon cuniculi, type strain III (the dog genotype),
      based on ultrastructure, antigenic characteristics, PCR, and the sequence of the
      ribosomal DNA internal transcribed spacer region.

PMID- 11230436
TI  - Detection of Treponema denticola in atherosclerotic lesions.
AB  - We examined 26 atherosclerotic lesions and 14 nondiseased aorta specimens to
      detect the periodontopathogenic part of the bacterial 16S rRNA locus by PCR.
      Treponema denticola sequence of the 16S rRNA locus was found in 6 out of 26 DNA
      samples (23.1%) from the formalin-fixed, paraffin-embeded atherosclerotic lesions
      obtained during surgery but not in any of the 14 nondiseased aorta samples from
      deceased persons. Utilizing immunofluorescence microscopy, we observed aggregated
      antigenic particles reacting with rabbit antiserum against T. denticola in thin
      sections of the PCR-positive samples, but we could not detect any reacting
      particles in the PCR-negative thin sections.

PMID- 11230437
TI  - Effect of errors in the sequence of optical densities from the Roche AMPLICOR HIV
      1 MONITOR assay on the validity of assay results.
AB  - Specifications for the AMPLICOR HIV-1 MONITOR kit indicate that the results are
      invalid if the optical densities (ODs) from the PCR-amplified sample that are
      between 0.1 and 2.3 units are out of sequence. However, among 11,904 assays,
      results were biased only when ODs of 0.2 to 2.0 units were out of sequence,
      reducing the rate of invalid results from 3.2 to 0.59%.

PMID- 11230438
TI  - Multisite comparison of reproducibility and recovery from the standard and
      ultrasensitive Roche AMPLICOR HIV-1 MONITOR assays.
AB  - Reproducibility and recovery from the standard and ultrasensitive Roche AMPLICOR
      HIV-1 MONITOR kits were compared in 19 laboratories. The results were generally
      similar, but the consistently low level of recovery from the ultrasensitive assay
      in one laboratory points to the need to include external controls in order to
      track assay performance.

PMID- 11230440
TI  - Rapid typing of Borrelia burgdorferi sensu lato species in specimens from
      patients with different manifestations of Lyme borreliosis.
AB  - To further investigate the pathogenic potential of different Borrelia burgdorferi
      genospecies, specimens from 27 patients with different manifestations of Lyme
      borreliosis were analyzed by PCR and reverse line blotting (RLB). In samples from
      Lyme arthritis patients, B. burgdorferi sensu stricto was predominantly
      identified, while in patients with neuroborreliosis or acrodermatitis, Borrelia
      garinii and Borrelia afzelii, respectively, were exclusively detected. The
      results demonstrate that PCR-RLB is a valuable tool for epidemiological and
      pathogenetic studies of Lyme borreliosis.

PMID- 11230441
TI  - Cutaneous infection caused by Aspergillus ustus, an emerging opportunistic fungus
      in immunosuppressed patients.
AB  - We report a case of primary cutaneous infection by the emerging fungus
      Aspergillus ustus in an immunosuppressed patient after a domestic accident. The
      patient failed to respond to itraconazole and died before receiving a new
      treatment with amphotericin B. There have been eight other cases reported since
      1973, and only two patients survived the infection. In vitro susceptibility
      testing of seven antifungal drugs showed that terbinafine and the new azole
      derivative UR-9825 were the most active against this fungus.

PMID- 11230439
TI  - In vitro evolution of the human immunodeficiency virus type 1 gag-protease region
      and maintenance of reverse transcriptase resistance following prolonged drug
      exposure.
AB  - We studied the human immunodeficiency virus type 1 phenotypic and genotypic
      profiles of a dual drug-resistant isolate (isolate 14aPost-DR) selected for
      zidovudine (ZDV) and lamivudine (3TC) resistance and then cultured in the
      presence of 3TC and a protease inhibitor: indinavir (IDV), ritonavir, or KNI-272.
      The IDV-treated virus was highly resistant to 3TC, ZDV, and IDV and accumulated
      protease mutations at positions M46I and V82F. A change from alanine to valine
      was observed in 4 of 10 clones in the P2 position of the p7-p1 Gag-protease
      cleavage site, linked to position M46I in the dominant viral quasispecies.
      Previous 3TC resistance did not impair the development of additional mutations in
      the protease and Gag-protease cleavage regions.

PMID- 11230442
TI  - Heterogeneity of Pneumocystis sterol profiles of samples from different sites in
      the same pair of lungs suggests coinfection by distinct organism populations.
AB  - Sterol profiles of samples taken from different sites of a Pneumocystis-infected
      human lung showed large variations in pneumocysterol similar to those that occur
      among samples from different patients. Thus, the influence of diet or drugs on
      pneumocysterol accumulation was ruled out, suggesting distinct phenotypic
      populations as the basis for the heterogeneity.

PMID- 11230443
TI  - Phage types and genotypes of Shiga toxin-Producing Escherichia coli O157 in
      Finland.
AB  - This study examined Shiga toxin-producing Escherichia coli (STEC) O157, using
      phage typing, pulsed-field gel electrophoresis, and typing of Shiga toxin variant
      genes by PCR with restriction fragment length polymorphism in an epidemiological
      survey of STEC O157 isolated from humans in Finland between 1990 and 1999.

PMID- 11230444
TI  - Novel penicillin-, cephalosporin-, and macrolide-resistant clones of
      Streptococcus pneumoniae serotypes 23F and 19F in Taiwan which differ from
      international epidemic clones.
AB  - A cluster (14 of 18) of Streptococcus pneumoniae serotype 23F isolates that were
      resistant to penicillin (PEN), cephalosporin, and macrolide was found in one day
      care center in Kaohsiung, Taiwan. We analyzed the 18 isolates by pulsed field gel
      electrophoresis (PFGE). All but one serotype 23F isolate demonstrated identical
      PFGE patterns, which were different from the established pattern of the
      internationally spread Spanish 23F clone. The three strains of serotype 19F also
      showed a uniform pattern. These data strongly suggest that two novel clones of
      PEN-, cephalosporin-, and macrolide-resistant S. pneumoniae serotypes 23F and 19F
      are present in Taiwan.

PMID- 11230446
TI  - Yield of vancomycin-resistant enterococci and multidrug-resistant
      Enterobacteriaceae from stools submitted for Clostridium difficile testing
      compared to results from a focused surveillance program.
AB  - It has been suggested that a method of performing surveillance for vancomycin
      resistant enterococci (VRE) is to screen specimens submitted for Clostridium
      difficile testing. We compared this approach to our focused surveillance program
      of high-risk units during October 1997 to compare the yield of VRE and multidrug
      resistant Enterobacteriaceae (MDRE) with both methods. Of the stools submitted
      for C. difficile testing, 14% were positive for VRE or MDRE, whereas rectal swabs
      from routine surveillance yielded 11% VRE- or MDRE-positive results. Although
      stools submitted for C. difficile testing resulted in a higher percentage of
      positive cultures, 14 VRE- and 2 MDRE-positive patients from our high-risk
      population were missed because many patients had no stool submitted for C.
      difficile testing. Therefore, while screening stools submitted for C. difficile
      testing cannot replace our focused surveillance program, it appears advantageous
      to assess these stools at various intervals to detect new patient reservoirs of
      drug-resistant organisms that may benefit from routine surveillance cultures.

PMID- 11230445
TI  - Comparison of three nucleic acid amplification assays of cerebrospinal fluid for
      diagnosis of cytomegalovirus encephalitis.
AB  - The diagnostic reliabilities of three cytomegalovirus (CMV) nucleic acid
      amplification assays of cerebrospinal fluid (CSF) were compared by using CSF
      samples from human immunodeficiency virus-infected patients with a postmortem
      histopathological diagnosis of CMV encephalitis (n = 15) or other central nervous
      system conditions (n = 16). By using a nested PCR assay, the quantitative COBAS
      AMPLICOR CMV MONITOR PCR, and the NucliSens CMV pp67 nucleic acid sequence-based
      amplification assay, sensitivities were 93.3, 86.6, and 93.3%, respectively, and
      specificities were 93.7, 93.7, and 87.5%, respectively. The COBAS AMPLICOR assay
      revealed significantly higher CMV DNA levels in patients with diffuse
      ventriculoencephalitis than in patients with focal periventricular lesions.

PMID- 11230447
TI  - Quantitation of porcine cytomegalovirus in pig tissues by PCR.
AB  - A quantitative-competitive PCR for the quantification of porcine cytomegalovirus
      (PCMV) was developed. The virus was detected in a variety of pig organs
      (including potential xenotransplant donations), with viral loads ranging from <10
      to 97 genome copies/microg of DNA. This assay will have significant utility for
      studying the activation and replication of PCMV and in swine models for allo- and
      xenotransplantation.

PMID- 11230448
TI  - Rotavirus strains bearing genotype G9 or P[9] recovered from Brazilian children
      with diarrhea from 1997 to 1999.
AB  - Human rotavirus strains belonging to genotype G9 or P[9] were detected in a
      collection of stool specimens from children with diarrhea in two cities of the
      state of Rio de Janeiro, Brazil, between March 1997 and December 1999. G9 strains
      were first detected in April 1997 and remained prevalent until the end of the
      study, at a frequency of 15.9% (n = 157). A high percentage of VP7 nucleotide
      (99.0 to 99.5%) and deduced amino acid identity (98.6 to 99.1%) was found between
      three randomly selected Brazilian G9 strains and the American G9 strain US1205. A
      novel G9:P[4] genotype combination was detected in addition to G9:P[8] and
      G9:P[6], demonstrating that this G genotype may undergo constant genetic
      reassortment in nature. The P[9] rotavirus strains constituted 10.2%, the
      majority of which were detected between April and July 1997. The RNA
      electrophoretic migration pattern of the G3:P[9] strains resembled that of AU-1
      virus (G3:P3[9]), suggesting a genetic similarity between the Brazilian G3:P[9]
      strains and the Japanese virus, which is similar to a feline rotavirus
      genetically.

PMID- 11230449
TI  - Particular biochemical profiles for enterohemorrhagic Escherichia coli O157:H7
      isolates on the ID 32E system.
AB  - The ability of the ID 32E system to identify and discriminate 74 Escherichia coli
      O157 isolates among 106 E. coli non-O157 isolates was evaluated. The results
      showed atypical biochemical reactions but accurate identification at the species
      level and no unique biochemical profile numbers for E. coli O157, although these
      numbers were distinct from those of other serotypes.

PMID- 11230450
TI  - Possible horizontal transfer of the vanB2 gene among genetically diverse strains
      of vancomycin-resistant Enterococcus faecium in a Korean hospital.
AB  - A total of 25 isolates of vanB-containing Enterococcus faecium were recovered
      from patients in a single Korean hospital over a 20-month period. There were two
      distinct vanB2 patterns among the 11 pulsed-field gel electrophoresis types; 17
      contained the prototype vanB2 and 8 contained a novel vanB2 with a 177-bp
      deletion in vanY(B). Both vanB2 genes were transmissible in vitro at a mean
      frequency of 1.1 x 10(-8) transconjugants/donor. These results suggest the
      horizontal spread of vanB2 is occurring among genetically diverse strains of E.
      faecium in Korean hospitals.

PMID- 11230451
TI  - Transmission of Borrelia garinii OspA serotype 4 to BALB/c mice by Ixodes ricinus
      ticks collected in the field.
AB  - In Europe, Borrelia garinii OspA serotype 4 has been isolated from the
      cerebrospinal fluid of patients but, up to now, has never been identified among
      culture isolates from Ixodes ricinus ticks. This information raises the question
      of whether OspA serotype 4 is transmitted by I. ricinus in nature. In the present
      study, I. ricinus nymphs collected in an area of endemicity in southern Germany
      were allowed to feed on mice. Cultivation of ear biopsy specimens showed that six
      of seven B. garinii-infected mice were infected by OspA serotype 4. In contrast,
      very few B. garinii OspA serotype 4 organisms were isolated directly from the
      ticks which infected the mice; most isolates were B. afzelii. The infected mice
      transmitted mainly OspA serotype 4 to xenodiagnostic ticks, preferentially in
      combination with B. afzelii.

PMID- 11230452
TI  - Rapid identification of Candida glabrata based on trehalose and sucrose
      assimilation using Rosco diagnostic tablets.
AB  - We developed a simple method for the identification of Candida glabrata on the
      basis of the ability of this species to rapidly assimilate trehalose but not
      sucrose. After incubation of yeasts with Rosco diagnostic tablets containing
      sucrose or trehalose, identification of C. glabrata was achieved in 4 h with 100%
      sensitivity and specificity.

PMID- 11230453
TI  - Molecular epidemiology of Mycobacterium tuberculosis infection in Israel.
AB  - Restriction fragment length polymorphism analysis with IS6110 and DR-r probes was
      used to study 69 Mycobacterium tuberculosis isolates obtained from Israeli
      patients and new immigrants from the former Soviet Union and Ethiopia. DNA
      fingerprinting identified unique patterns for almost all isolates, indicating
      that most patients were infected with a unique strain imported from their country
      of origin and that their latent infection was reactivated in Israel.

PMID- 11230456
TI  - Antimicrobial resistance of Streptococcus pneumoniae recovered from outpatients
      with respiratory tract infections in Germany from 1998 to 1999: results of a
      national surveillance study.
AB  - Clinically significant pneumococcal isolates were prospectively collected from
      outpatients with respiratory tract infections by 19 different clinical
      microbiology laboratories in Germany. Resistance rates in a total of 961 isolates
      were as follows: penicillin, 6.6%; clarithromycin, 10.6%; tetracycline, 13.9%;
      and levofloxacin, 0.1%. Among 324 isolates from children, pneumococcal serotypes
      19F (17.0%), 23F (13.0%), and 6B (11.7%) were the predominant types.

PMID- 11230454
TI  - Molecular characterization of fliD gene encoding flagellar cap and its expression
      among Clostridium difficile isolates from different serogroups.
AB  - The fliD gene encoding the flagellar cap protein (FliD) of Clostridium difficile
      was studied in 46 isolates belonging to serogroups A, B, C, D, F, G, H, I, K, X,
      and S3, including 30 flagellated strains and 16 nonflagellated strains. In all
      but three isolates, amplification by PCR and reverse transcription-PCR
      demonstrated that the fliD gene is present and transcribed in both flagellated
      and nonflagellated strains. PCR-restriction fragment length polymorphism (RFLP)
      analysis of amplified fliD gene products revealed interstrain homogeneity, with
      one of two major patterns (a and b) found in all but one of the strains, which
      had pattern c. A polyclonal monospecific antiserum raised to the recombinant FliD
      protein reacted in immunoblots with crude flagellar preparations from 28 of 30
      flagellated strains but did not recognize FliD from nonflagellated strains. The
      fliD genes from five strains representative of the three different RFLP groups
      were sequenced, and sequencing revealed 100% identity between the strains with
      the same pattern and 88% identity among strains with different patterns. Our
      results show that even though FliD is a structure exposed to the outer
      environment, the flagellar cap protein is very well conserved, and this high
      degree of conservation suggests that it has a very specific function in
      attachment to cell or mucus receptors.

PMID- 11230455
TI  - Molecular detection of Mycoplasma pneumoniae in adults with community-acquired
      pneumonia requiring hospitalization.
AB  - Mycoplasma pneumoniae infection was diagnosed in 18 (12.5%) of 144 adults
      hospitalized with community-acquired pneumonia. The infection was demonstrated by
      PCR in 15 patients and by serology, using two methods, in 10 patients. The mean
      age of the 8 patients with positive M. pneumoniae PCR and negative serology was
      significantly higher than that of the 10 patients with positive serology.

PMID- 11230457
TI  - Isolation and characterization of a Salmonella enterica serotype Typhi variant
      and its clinical and public health implications.
AB  - We report the isolation and characterization of a member of the family
      Enterobacteriaceae isolated from the gallbladder pus of a food handler.
      Conventional biochemical tests suggested Salmonella enterica serotype Typhi, but
      the isolate agglutinated with poly(O), 2O, 9O, and Vi Salmonella antisera but not
      with poly(H) or any individual H Salmonella antisera. 16S rRNA gene sequencing
      showed that there were two base differences between the isolate and Salmonella
      enterica serotype Montevideo, four base differences between the isolate and
      serotype Typhi, five base differences between the isolate and Salmonella enterica
      serotype Typhimurium, and six base differences between the isolate and Salmonella
      enterica serotype Dublin, indicating that the isolate was a strain of S.
      enterica. Electron microscopy confirmed that the isolate was aflagellated. The
      flagellin gene sequence of the isolate was 100% identical to that of the H1-d
      flagellin gene of serotype Typhi. Sequencing of the rfbE gene, which encoded the
      CDP-tyvelose epimerase of the isolate, showed that there was a point mutation at
      position +694 (G-->T), leading to an amino acid substitution (Gly-->Cys). This
      may have resulted in a protein of reduced catalytic activity and hence the
      presence of both 2O and 9O antigens. We therefore concluded that the isolate was
      a variant of serotype Typhi. Besides antibiotic therapy and cholecystectomy,
      removal of all stones in the biliary tree was performed for eradication of the
      carrier state.

PMID- 11230459
TI  - Evaluation of a group-specific 16S ribosomal DNA-based PCR for detection of
      Helicobacter bizzozeronii, Helicobacter felis, and Helicobacter salomonis in
      fresh and paraffin-embedded gastric biopsy specimens.
AB  - A new specific and sensitive 16S ribosomal DNA-based PCR assay was developed. The
      assay targets a 78-bp DNA fragment unique to Helicobacter bizzozeronii,
      Helicobacter felis, and Helicobacter salomonis and can be used with freshly
      frozen and formalin-fixed paraffin-embedded gastric biopsy specimens.

PMID- 11230458
TI  - Comparison of IsoCode STIX and FTA Gene Guard collection matrices as whole-blood
      storage and processing devices for diagnosis of malaria by PCR.
AB  - We compared two collection devices, IsoCode and FTA, with whole blood for the
      diagnosis of malaria by PCR (n = 100). Using whole blood as the reference
      standard, both devices were sensitive for the detection of single-species malaria
      infections by PCR (> or =96%). However, the detection of mixed infections was
      suboptimal (IsoCode was 42% sensitive, and FTA was 63% sensitive).

PMID- 11230460
TI  - Recurrent self-limited fungemia caused by Yarrowia lipolytica in a patient with
      acute myelogenous leukemia.
AB  - Yarrowia lipolytica is a weakly pathogenic yeast that is rarely isolated from the
      blood. We observed transient recurrent catheter-related fungemia attributable to
      this organism in a leukemic patient. The fungemia and accompanying fever subsided
      spontaneously. The data suggest that it might be possible to withhold specific
      treatment for Y. lipolytica fungemia even in an immunocompromised patient.

PMID- 11230461
TI  - Case of synovitis potentially caused by Dolosigranulum pigrum.
AB  - We report a case of synovitis in a 64-year-old man who developed the infection
      while on steroid therapy for rheumatoid arthritis. Dolosigranulum pigrum, a gram
      positive catalase-negative coccus, was isolated from two sets of blood cultures
      prior to antibiotic therapy. The patient was treated with 4 weeks of appropriate
      antibiotics, and the synovial inflammation resolved. Although synovial aspirates
      were never positive for any bacteria or fungi, the timing of positive blood
      cultures and absence of other pathogens suggest the possible etiology as D.
      pigrum.

PMID- 11230462
TI  - Molecular evidence of male-to-female sexual transmission of hepatitis C virus
      after vaginal and anal intercourse.
AB  - Hepatitis C virus (HCV) was transmitted from a chronic carrier to his female
      partner during unprotected anal and vaginal intercourse. Based on HVR1 and
      phylogenetic tree analysis, the couple had closely related isolates. These
      findings confirm sexual transmission of HCV without other risk factors.

PMID- 11230463
TI  - Adjuvant chemotherapy for adult soft tissue sarcoma: Is there a standard of care?

PMID- 11230464
TI  - Adjuvant chemotherapy for adult soft tissue sarcomas of the extremities and
      girdles: results of the Italian randomized cooperative trial.
AB  - PURPOSE: Adjuvant chemotherapy for soft tissue sarcoma is controversial because
      previous trials reported conflicting results. The present study was designed with
      restricted selection criteria and high dose-intensities of the two most active
      chemotherapeutic agents. PATIENTS AND METHODS: Patients between 18 and 65 years
      of age with grade 3 to 4 spindle-cell sarcomas (primary diameter > or = 5 cm or
      any size recurrent tumor) in extremities or girdles were eligible. Stratification
      was by primary versus recurrent tumors and by tumor diameter greater than or
      equal to 10 cm versus less than 10 cm. One hundred four patients were randomized,
      51 to the control group and 53 to the treatment group (five cycles of 4'
      epidoxorubicin 60 mg/m(2) days 1 and 2 and ifosfamide 1.8 g/m(2) days 1 through
      5, with hydration, mesna, and granulocyte colony-stimulating factor). RESULTS:
      After a median follow-up of 59 months, 60 patients had relapsed and 48 died (28
      and 20 in the treatment arm and 32 and 28 in the control arm, respectively). The
      median disease-free survival (DFS) was 48 months in the treatment group and 16
      months in the control group (P =.04); and the median overall survival (OS) was 75
      months for treated and 46 months for untreated patients (P =.03). For OS, the
      absolute benefit deriving from chemotherapy was 13% at 2 years and increased to
      19% at 4 years (P =.04). CONCLUSION: Intensified adjuvant chemotherapy had a
      positive impact on the DFS and OS of patients with high-risk extremity soft
      tissue sarcomas at a median follow-up of 59 months. Therefore, our data favor an
      intensified treatment in similar cases. Although cure is still difficult to
      achieve, a significant delay in death is worthwhile, also considering the short
      duration of treatment and the absence of toxic deaths.

PMID- 11230466
TI  - Phase I and pharmacokinetic study of ecteinascidin-743, a new marine compound,
      administered as a 24-hour continuous infusion in patients with solid tumors.
AB  - PURPOSE: To define the maximum-tolerated dose (MTD) and the phase II recommended
      dose (RD) of ecteinascidin-743 (ET-743) given as a 24-hour continuous infusion
      every 3 weeks to patients with treatment-refractory solid tumors. PATIENTS AND
      METHODS: Fifty-two patients received a total of 158 cycles of ET-743 at one of
      nine dose levels (DLs) ranging from 50 to 1,800 microg/m(2). RESULTS: The MTD was
      defined as 1,800 microg/m(2) (DL 9), and the phase II RD was 1,500 microg/m(2)
      (DL 8) for moderately pretreated patients with performance status (PS) 0 to 1 and
      good hepatobiliary function. Neutropenia and thrombocytopenia were the dose
      limiting toxicities (DLTs) and were severe at the MTD (1,800 microg/m(2)) in 94%
      and 25% of cycles, respectively. At the RD (1,500 microg/m(2)), neutropenia and
      thrombocytopenia were present in 33% and 10% of cycles, respectively. Transient
      acute elevated transaminase levels occurred in almost all cycles and was severe
      in 38% of cycles. Severe toxicities and DLTs were observed in patients with poor
      PS or abnormal liver function or who had received a large number of previous
      chemotherapy regimens. Antitumor activity was observed at the three highest DLs,
      including three partial responses (breast cancer, osteosarcoma, and liposarcoma),
      and four patients (all with progressing soft tissue sarcomas) had stable disease
      lasting > or = 3 months. Pharmacokinetic studies were performed on all patients
      for at least the first cycle, giving a linear pharmacokinetic profile; this
      showed a relationship between area under the curve (AUC) and transaminitis grade
      and a clear correlation between AUC and severe hematologic toxicity likelihood.
      CONCLUSION: The RD for a 24-hour continuous intravenous infusion of ET-743 is
      1,500 microg/m(2), with the most prevalent DLTs being hematologic. Patients with
      minor baseline hepatobiliary function abnormalities have a higher likelihood of
      severe hematologic toxicities and AUC-related DLTs, requiring dose adjustments or
      delays.

PMID- 11230467
TI  - Does palliative chemotherapy palliate? Evaluation of expectations, outcomes, and
      costs in women receiving chemotherapy for advanced ovarian cancer.
AB  - PURPOSE: The value of palliative chemotherapy in women with refractory and
      recurrent ovarian cancer is difficult to quantify, and little is known about
      patient expectations from these treatments. We evaluated in the current
      prospective study patient expectations, palliative outcomes of chemotherapy, and
      the inherent resource utilization in patients undergoing second- or third-line
      chemotherapy for recurrent or refractory advanced ovarian cancer. METHODS: The
      European Organization for Research and Treatment of Cancer Quality-of-Life
      Questionnaire C30 (EORTC QLQ C30) and Functional Assessment of Cancer Therapy
      Ovarian (FACT-O) questionnaires were used to assess palliative benefit and an in
      house questionnaire was used to gauge patient expectations. The minimal
      clinically important difference (MCID) was calculated by asking women to make a
      global rating of change and correlating this to the EORTC QLQ C30. Resource use
      was recorded and costs were calculated. RESULTS: Twenty-seven patients were
      accrued. Objective response was documented on seven of 27. The median survival
      was 11 months. Sixty-five percent of women expected that chemotherapy would make
      them live longer and 42% that it would cure them. After two cycles, quality-of
      life (QL) improvement was seen particularly in global function (11 of 21) and
      emotional function (13 of 21) with EORTC QLQ C-30. Improvement was sustained for
      a median of 2 and 3 months, respectively, in these categories. The MCID was
      calculated to be 0.39 on a seven-point scale for physical function and 0.13 for
      global function. The mean total cost per patient for the study period was Can
      $12,500. CONCLUSION: Patient expectations from these treatments are often
      unrealistic. Although objective responses are low, active palliation with
      chemotherapy is associated with substantive improvement in patients' emotional
      function and global QL, with overall costs that seem relatively modest.

PMID- 11230465
TI  - Ecteinascidin-743: a marine-derived compound in advanced, pretreated sarcoma
      patients--preliminary evidence of activity.
AB  - PURPOSE: To report the activity of the chemotherapeutic agent ecteinascidin-743
      (ET-743) in advanced pretreated sarcoma patients observed during a phase I study
      and a named-patient basis, compassionate use program. PATIENTS AND METHODS:
      Twenty-nine pretreated, advanced soft tissue sarcoma (STS) and bone sarcoma
      patients consecutively seen in our centers were included, 12 from a phase I trial
      and 17 from a compassionate use program cohort. Patients were treated every 3
      weeks at either 1,200 microg/m(2) (six patients), 1,500 microg/m(2) (the
      recommended dose, 22 patients), or 1,800 microg/m(2) (the maximum-tolerated dose,
      one patient), given as a 24-hour infusion every 3 to 4 weeks. RESULTS: Fifteen
      men and 14 women were treated. The median patient age was 46 years (range, 16 to
      71 years), with a median World Health Organization performance status of 1
      (range, 0 to 2). Twenty-five patients had STS, three had osteosarcoma, and one
      had Ewing's sarcoma, and all had progressive disease at accrual. Fifteen patients
      had bulky disease, and 14 had clinical resistance to anthracyclines. A total of
      136 treatment cycles were administered (median per patient, five cycles; range,
      one to 12 cycles). Transient grade 3 and 4 transaminitis was reported in 24% and
      5% of cycles, respectively, grade 3 to 4 neutropenia occurred in 32% of cycles,
      with concomitant sporadic grade 3 to 4 thrombocytopenia in 5.1% of cycles. Grade
      2 to 3 asthenia occurred in 21% of cycles. There were two partial responses (PRs)
      in STS patients and two PRs in osteosarcoma patients. Two minor responses and 10
      disease stabilizations were seen. Median duration of response was 10.5 months
      (range, 2.8 to 15 months), and mean duration of stabilization was 5.2 months.
      CONCLUSION: ET-743 has activity in advanced, highly pretreated STS and
      osteosarcoma patients and warrants further trials to establish the extent of its
      activity in this setting.

PMID- 11230468
TI  - Paclitaxel, an active agent in nonsquamous carcinomas of the uterine cervix: a
      Gynecologic Oncology Group Study.
AB  - PURPOSE: A phase II trial of paclitaxel was initiated in advanced nonsquamous
      carcinoma of the cervix to determine its activity in patients who had failed
      standard chemotherapy. PATIENTS AND METHODS: Eligible patients had at least one
      measurable lesion. The starting dose of paclitaxel was 170 mg/m(2) (135 mg/m(2)
      for patients with prior pelvic radiation) given as a 24-hour continuous
      intravenous infusion with courses repeated every 3 weeks. Dose escalation to 200
      mg/m(2) and de-escalation to 110 mg/m(2) were allowed based on adverse effects.
      RESULTS: In this trial, 42 assessable patients were initially entered onto the
      study, and 13 responses were seen; four patients had a complete response, and
      nine patients had a partial response. The overall response rate was 31%. The
      primary and dose-limiting toxicity was neutropenia. CONCLUSION: The response rate
      to paclitaxel exceeds the rates reported using other single agents in nonsquamous
      carcinoma of the cervix.

PMID- 11230469
TI  - Glutathione S-transferase polymorphisms and outcome of chemotherapy in childhood
      acute myeloid leukemia.
AB  - PURPOSE: Glutathione S-transferase theta (GSTT1) and mu (GSTM1) genes are
      polymorphic, the genes being absent in approximately 15% and 50% of the
      population, respectively. Because glutathione S-transferases may be involved in
      the metabolism of chemotherapy drugs, we hypothesized that presence or absence of
      the genes may influence the outcome of treatment for childhood acute myeloid
      leukemia (AML). PATIENTS AND METHODS: We genotyped GSTT1 and GSTM1 in 306
      children with AML receiving chemotherapy on Children's Cancer Group therapeutic
      studies. Outcomes were compared in those with and without GSTT1 and GSTM1 genes.
      RESULTS: Patients with the GSTT1-negative genotype had reduced survival compared
      with those with at least one GSTT1 allele (GSTT1 positive) (52% v 40% at 5 years;
      log-rank P =.05). A multivariate model of survival adjusted for age group, sex,
      WBC count, chloroma, CNS involvement, and French-American-British group confirmed
      the increased risk of death in the GSTT1-null cases (relative risk, AQ 1.6; P
      =.02). The frequency of death in remission was increased in GSTT1-negative cases
      compared with GSTT1-positive cases (24% v 12%, log-rank P =.05). The frequency of
      relapse from end of induction was similar in GSTT1-negative and GSTT1-positive
      cases (38% v 35%, log-rank P =.5). CONCLUSION: Children who lacked GSTT1 had
      greater toxicity and reduced survival after chemotherapy for AML compared with
      children with at least one GSTT1 allele. If confirmed in further studies, GSTT1
      genotype might be useful in selecting appropriate chemotherapy regimens for
      children with AML.

PMID- 11230470
TI  - Postoperative chemotherapy without irradiation for ependymoma in children under 5
      years of age: a multicenter trial of the French Society of Pediatric Oncology.
AB  - PURPOSE: To evaluate a strategy that avoids radiotherapy in first-line treatment
      in children under 5 years of age with brain or posterior fossa ependymoma, by
      exclusively administering 16 months of adjuvant multiagent chemotherapy after
      surgery. PATIENTS AND METHODS: Between June 1990 and October 1998, 73 children
      with ependymoma (82% with high-grade tumors) were enrolled onto this multicenter
      trial. Children received adjuvant conventional chemotherapy after surgery
      consisting of seven cycles of three courses alternating two drugs at each course
      (procarbazine and carboplatin, etoposide and cisplatin, vincristine and
      cyclophosphamide) over a year and a half. Systematic irradiation was not
      envisaged at the end of chemotherapy. In the event of relapse or progression,
      salvage treatment consisted of a second surgical procedure followed by local
      irradiation with or without second-line chemotherapy. RESULTS: Conventional
      chemotherapy was well tolerated and could be administered in outpatient clinics.
      No radiologically documented response to chemotherapy more than 50% was observed.
      With a median follow-up of 4.7 years (range, 5 months to 8 years), the 4-year
      progression-free survival rate in this series was 22% (95% confidence interval
      [CI], 13% to 43%) and the overall survival rate was 59% (95% CI, 47% to 71%).
      Overall, 40% (95% CI, 29% to 51%) of the patients were alive having never
      received radiotherapy 2 years after the initiation of chemotherapy and 23% (95%
      CI, 14% to 35%) were still alive at 4 years without recourse to this modality. In
      the multivariate analysis, the two factors associated with a favorable outcome
      were a supratentorial tumor location (P =.0004) and complete surgery (P =.0009).
      Overall survival at 4 years was 74% (95% CI, 59% to 86%) for the patients in whom
      resection was radiologically complete and 35% (95% CI, 18% to 56%) for the
      patients with incomplete resection. CONCLUSION: A significant proportion of
      children with ependymoma can avoid radiotherapy with prolonged adjuvant
      chemotherapy. Deferring irradiation at the time of relapse did not compromise
      overall survival of the entire patient population.

PMID- 11230471
TI  - Effect of protracted high-dose L-asparaginase given as a second exposure in a
      Berlin-Frankfurt-Munster-based treatment: results of the randomized 9102
      intermediate-risk childhood acute lymphoblastic leukemia study--a report from the
      Associazione Italiana Ematologia Oncologia Pediatrica.
AB  - PURPOSE: To assess in a randomized study the therapeutic effect of the addition
      of high-dose L-asparaginase (HD ASP) in the context of a Berlin-Frankfurt-Munster
      (BFM)-based chemotherapy regimen for intermediate risk (IR) childhood acute
      lymphoblastic leukemia (ALL). PATIENTS AND METHODS: From March 1991 to April
      1995, a total of 705 patients, with 59% of the cohort of patients fewer than 15
      years old, with newly diagnosed non-B ALL, enrolled onto the Associazione
      Italiana Ematologia Oncologia Pediatrica (AIEOP) ALL-91 study, were assigned to
      the IR group. Patients in remission at the beginning of the reinduction phase
      were randomized either to the standard treatment (SD ASP arm) or the experimental
      treatment (HD ASP arm; weekly intramuscular administration of HD ASP 25,000
      IU/m(2) repeated for a total of 20 weeks). Most of the patients (90%) were
      treated with Erwinia chrysanthemi L-asparaginase product. RESULTS: Among the 610
      patients randomized to the SD ASP arm (n = 322) or to the HD ASP arm (n = 288),
      relapse occurred at a median time of 24 months after randomization in 76 (24%)
      and in 64 children (22%), respectively. Most of the relapses occurred in the
      marrow (100 isolated, 21 combined). There was no significant difference between
      the disease-free survival in the two treatment arms (P =.64), with estimated
      values at 7 years from randomization of 72.4% (SE 3.1) v 75.7% (SE 2.6) in the SD
      ASP and HD ASP arms, respectively. CONCLUSION: No advantage was observed for IR
      ALL children treated with BFM-based intensive chemotherapy who received
      protracted E chrysanthemi HD ASP during reinduction and the early continuation
      phase.

PMID- 11230472
TI  - Serum prostate-specific antigen decline as a marker of clinical outcome in
      hormone-refractory prostate cancer patients: association with progression-free
      survival, pain end points, and survival.
AB  - PURPOSE: Validated end points are lacking for clinical trials in hormone
      refractory prostate cancer (HRPC). Controversy remains regarding the utility of a
      posttreatment decline of prostate-specific antigen (PSA). The purpose of this
      study was to determine whether posttreatment declines in PSA were associated with
      clinical measures of improvement in a randomized phase III trial of suramin plus
      hydrocortisone versus placebo plus hydrocortisone. PATIENTS AND METHODS: A total
      of 460 HRPC patients were randomized to receive suramin plus hydrocortisone (n =
      229) or placebo plus hydrocortisone (n = 231). All patients had symptomatic,
      metastatic HRPC requiring opioid analgesics. Clinical end points evaluated
      included overall survival, objective progression-free survival (OPFS), and time
      to pain progression (TTPP). An evaluation of overall survival, OPFS, and TTPP as
      a function of a PSA decline of > or = 50%, lasting at least 28 days, was
      undertaken by using a landmark analysis at 6, 9, and 12 weeks. A multivariate
      analysis of the impact of PSA decline was performed on these clinical end points.
      RESULTS: A decline in PSA of > or = 50% lasting > or = 28 days was significantly
      associated with a prolonged median overall survival, OPFS, and TTPP, both in the
      entire group and the suramin plus hydrocortisone group at all three landmarks in
      both univariate and multivariate analysis. CONCLUSION: In this prospective,
      randomized trial of suramin plus hydrocortisone versus placebo plus
      hydrocortisone, a posttherapy decline in PSA of > or = 50%, lasting 28 days, was
      associated with prolonged median overall survival, improved median progression
      free survival, and median TTPP. This analysis suggests that a posttreatment
      decline in PSA may be a reasonable intermediate end point in HRPC trials and
      calls into question the clinical utility of preclinical assays evaluating the in
      vitro effect of given agents on PSA secretion.

PMID- 11230473
TI  - Phase I trial of 40-kd branched pegylated interferon alfa-2a for patients with
      advanced renal cell carcinoma.
AB  - PURPOSE: Pegylated (40 kd) interferon alfa-2a (IFNalpha2a) (PEGASYS, Hoffman-La
      Roche, Nutley, NJ; PEG-IFN) is a modified form of recombinant human IFNalpha2a
      with sustained absorption and prolonged half-life after subcutaneous
      administration. A phase I study of PEG-IFN with pharmacokinetic and
      pharmacodynamic evaluations was conducted in previously untreated patients with
      advanced renal cell carcinoma (RCC). PATIENTS AND METHODS: Twenty-seven patients
      were enrolled onto cohorts of three or six patients. PEG-IFN was administered on
      a weekly basis by subcutaneous injection. The dose was escalated from 180
      microg/wk to a maximum of 540 microg/wk in 90-microg increments. Serial venous
      blood samples were drawn to assess concentrations of PEG-IFN and two immunologic
      surrogates, neopterin and 2'-5' oligoadenylate synthetase (OAS). RESULTS: The
      maximum-tolerated dose was determined as 540 microg/wk, because two patients
      experienced dose-limiting toxicity within 28 days of starting treatment. One
      developed serum grade 3 ALT elevation, and a second developed grade 3 fatigue.
      Six patients were treated at 450 microg/wk without dose-limiting toxicity. Over
      the course of treatment, the side-effect profile was mostly mild to moderate in
      intensity. Adverse events included fatigue, fever, headache, myalgia, nausea, and
      decreased appetite. Five patients (19%) achieved a partial response. The mean
      maximum serum concentration increased from 5.0 to 27 ng/mL, and mean area under
      the curve increased from 247 to 2,981 ng/h/mL, with dose escalation from 180
      microg/wk to 540 microg/wk. Serum concentration of PEG-IFN was sustained at close
      to peak during the dosing interval, and steady-state was achieved in
      approximately 5 weeks. The immunologic surrogates, neopterin and OAS, were
      induced at all doses with a sustained concentration profile similar to PEG-IFN.
      CONCLUSION: PEG-IFN is a modified form of IFNalpha2a with distinct
      pharmacokinetic advantages and immunomodulatory and antitumor activity for
      patients with advanced RCC. A dose of 450 microg/wk by subcutaneous
      administration was determined as a suitable dose for further study. PEG-IFN is
      more convenient to administer than IFNalpha and has potential for increased
      efficacy, less toxicity, or both. The efficacy and toxicity of PEG-IFN will be
      further assessed in clinical trials and compared with IFNalpha.

PMID- 11230474
TI  - Phase II trial of paclitaxel and carboplatin in metastatic small-cell lung
      cancer: a Groupe Francais de Pneumo-Cancerologie study.
AB  - PURPOSE: To evaluate the efficacy and safety of paclitaxel and carboplatin in the
      treatment of previously untreated patients with metastatic small-cell lung cancer
      (SCLC). PATIENTS AND METHODS: Eligible patients were aged 18 to 75 years with an
      Eastern Cooperative Oncology Group (ECOG) score < or = 2 and life expectancy > or
      = 12 weeks. Paclitaxel (200 mg/m(2)) was infused over 3 hours, before carboplatin
      (area under the curve [AUC] 6; Calvert formula) infused over 1 hour, once every 3
      weeks for six cycles maximum. Prednisolone, dexchlorpheniramine, and ranitidine
      were standard premedication. Response to treatment was assessed every two cycles,
      and nonresponding patients were withdrawn from the trial to receive standard
      chemotherapy. RESULTS: Of the 50 patients entering the study, 48 and 46 patients
      were assessable for toxicity and response, respectively. The overall response
      rate was 65%, with complete responses in three patients. Five patients had stable
      disease (11%) and 11 patients experienced progressive disease (24%). Median
      survival was 38 weeks, and median duration of response was 20 weeks. One-year
      survival was 22.5%. For a total of 232 cycles, grade 3 and 4 toxicity was 33% for
      neutropenia, 3.5% for thrombocytopenia, and 4% for anemia. Four patients had
      neutropenic fever (one toxic death). Nonhematologic toxicity was mainly grade 1
      and 2 paresthesia (21% of patients); grade 3 myalgia/arthralgia was observed in
      6.5% of patients. CONCLUSION: First-line chemotherapy with paclitaxel and
      carboplatin in metastatic SCLC achieved a response rate and survival similar to
      standard regimens. With 1-day administration and a tolerable toxicity profile,
      this combination merits further investigation.

PMID- 11230475
TI  - Phase I study of a decision aid for patients with locally advanced non-small-cell
      lung cancer.
AB  - PURPOSE: Many patients with locally advanced non-small-cell lung cancer (LA
      NSCLC) are eligible for combined-modality therapy (CMT; chemotherapy and
      radiotherapy). Although CMT offers slightly higher chances of survival than
      radiotherapy alone (RT), it also carries a higher probability of toxicity,
      raising the possibility that some patients may prefer to decline CMT. We report a
      pilot study of a decision aid designed for patients in this setting. PATIENTS AND
      METHODS: The aid included a structured description of the treatment options and
      trade-off exercises designed to help clarify the patient's values for the
      relevant outcomes by determining the patient's survival advantage threshold (SAT;
      the increase in survival conferred by CMT over RT that the patient deemed
      necessary for choosing CMT). Additional outcome measures included each patient's
      strength of treatment preference, decisional conflict, objective understanding of
      survival information, and decisional role preference. RESULTS: Twenty-seven
      patients met the eligibility criteria for the study. Of these, seven declined the
      decision aid because they had a clear treatment preference. The remaining 20
      participants completed the decision aid; 18 chose CMT, and two chose RT. All 20
      patients wished to participate in the decision to some extent. All patients
      reported that using the decision support was useful to them and recommended its
      use for others. No patient or physician reported that the aid interfered with the
      physician-patient relationship. Patients' 3-year SATs and median SATs were each
      strongly correlated with their strengths of treatment preference (rho = 0.83, P
      <.001 and rho = 0.67, P =.02, respectively). For all but one patient, either
      their 3-year or median survival threshold was consistent with their final
      treatment choice. Ten patients reported a stronger treatment preference after
      using the decision aid. CONCLUSION: We conclude that implementing the decision
      aid for patients with LA-NSCLC is feasible, that it demonstrates convergent
      validity, and that it is favorably evaluated by patients and their physicians.
      The aid seems to help patients understand the benefits and risks of treatment and
      to choose the treatment that is most consistent with their values. Further
      evaluation of the aid is warranted.

PMID- 11230476
TI  - Duration of chemotherapy in advanced non-small-cell lung cancer: a randomized
      trial of three versus six courses of mitomycin, vinblastine, and cisplatin.
AB  - PURPOSE: So far there are no published data on optimal duration of chemotherapy
      for advanced non-small-cell lung cancer (NSCLC); six or more courses are usually
      recommended. We have carried out a multicenter randomized trial comparing three
      versus six courses of chemotherapy. PATIENTS AND METHODS: Patients with stage
      IIIb or IV NSCLC were randomized at start of treatment to receive either three or
      six courses of mitomycin 8 mg/m(2) (courses 1, 2, 4, and 6), vinblastine 6
      mg/m(2), and cisplatin 50 mg/m(2) (MVP) every 21 days. Treatment was stopped
      early in both arms for progressive disease or unacceptable toxicity. Key end
      points were overall survival, duration of symptom relief, and quality-of-life
      assessment using the European Organization for Research and Treatment of Cancer
      (EORTC) core questionnaire QLQ-C30 with lung cancer-specific module QLQ-LC13.
      RESULTS: Three hundred eight patients were randomized. Seventy-two percent of the
      155 patients randomized to three courses completed treatment. In the 153 patients
      randomized to six courses, 73% completed three courses and 31% six courses.
      Median survival was 6 versus 7 months, respectively, and 1-year survival 22%
      versus 25% (P =.2). Median duration of symptom relief was 4.5 months (both arms),
      and 8% versus 18% had continuing symptom relief (P =.4). Quality-of-life
      parameters were the same or improved for patients randomized to only three
      courses, including significantly decreased fatigue (P =.03) and a trend toward
      decreased nausea and vomiting (P =.06). CONCLUSION: Our findings show no evidence
      for additional clinical benefit by continuing MVP chemotherapy beyond three
      courses. This challenges current orthodoxy of six courses or more. Further trials
      addressing duration of chemotherapy are now warranted, particularly with newer
      chemotherapy schedules.

PMID- 11230477
TI  - Factors affecting the risk of brain metastases after definitive chemoradiation
      for locally advanced non-small-cell lung carcinoma.
AB  - PURPOSE: As therapy for locally advanced non-small-cell lung carcinoma (NSCLC)
      improves, brain metastases (BM) may become a greater problem. We analyzed our
      chemoradiation experience for patients at highest risk for the brain as the first
      failure site. METHODS: Records for 150 consecutive patients with stage II/III
      NSCLC treated definitively with chemoradiation from June 1992 to June 1998 at the
      University of Pennsylvania were reviewed. Most patients (89%) received cisplatin,
      paclitaxel, or both. All had negative brain imaging before treatment.
      Posttreatment brain imaging was performed for suspicious symptoms. Incidence of
      BM was examined as a function of age, sex, histology, stage, performance status,
      weight loss, tumor location, surgery, radiation dose, initial radiation field,
      chemotherapy regimen, and chemotherapy timing. RESULTS: Crude and 2-year
      actuarial rates of BM were 19% and 30%, respectively. Among pretreatment
      parameters, stage IIIB was associated with a higher risk of BM (P <.04) versus
      stage II/IIIA. Histology alone was not significant (P <.12), although patients
      with IIIB nonsquamous tumors had an exceptionally high 2-year BM rate of 42% (P
      <.01 v all others). Examining treatment-related parameters, crude and 2-year
      actuarial risk of BM were 27% and 39%, respectively, in patients receiving
      chemotherapy before radiotherapy and 15% and 20%, respectively, when radiotherapy
      was not delayed (P <.05). On multivariate analysis, timing of chemotherapy (P
      <.01) and stage IIIA versus IIIB (P <.01) remained significant. CONCLUSION:
      Patients with later stage, nonsquamous NSCLC, particularly those receiving
      induction chemotherapy, have sufficiently common BM rates to justify future
      trials including prophylactic cranial irradiation.

PMID- 11230478
TI  - Results of a prospective randomized trial comparing neoadjuvant chemotherapy plus
      radiotherapy with radiotherapy alone in patients with locoregionally advanced
      nasopharyngeal carcinoma.
AB  - PURPOSE: A prospective randomized trial was performed to evaluate the
      contribution of neoadjuvant chemotherapy in patients with locoregionally advanced
      nasopharyngeal carcinoma. PATIENTS AND METHODS: Patients with locoregionally
      advanced nasopharyngeal carcinoma were treated either with radiotherapy alone (RT
      group) or neoadjuvant chemotherapy plus radiotherapy (CT/RT group). Neoadjuvant
      chemotherapy consisting of two to three cycles of cisplatin (100 mg/m(2), day 1),
      bleomycin (10 mg/m(2), days 1 and 5), and fluorouracil (5-FU; 800 mg/m(2), days 1
      through 5, continuous infusion) followed by radiotherapy was given to the CT/RT
      group. All patients were treated in a uniform fashion by definitive-intent
      radiation therapy in both groups. RESULTS: Between July 1993 and July 1994, 456
      patients were entered onto the study, with 228 patients randomized to each
      treatment arm, and 449 patients (225 in the RT group and 224 in the CT/RT group)
      were assessable. All 456 patients were included in survival analysis according to
      the intent-to-treat principle. The 5-year overall survival (OS) rates were 63%
      for the CT/RT group and 56% for the RT group (P =.11). The median relapse-free
      survival (RFS) time was 50 months for the RT group and not reached for the CT/RT
      group. The 5-year RFS rate was 49% for the RT group versus 59% for the CT/RT
      group (P =.05). The 5-year freedom from local recurrence rate was 82% for the
      CT/RT group and 74% for the RT group (P =.04). There was no significant
      difference in freedom from distant metastasis between the two treatment groups
      (CT/RT group, 79%; RT group, 75%; P =.40). CONCLUSION: This randomized study
      failed to demonstrate any significant survival benefit with the addition of
      neoadjuvant chemotherapy for patients with locoregionally advanced nasopharyngeal
      carcinoma. Therefore, neoadjuvant chemotherapy for nasopharyngeal carcinoma
      should not be used outside of the context of a clinical trial.

PMID- 11230479
TI  - Synchronous and metachronous squamous cell carcinomas of the head and neck
      mucosal sites.
AB  - PURPOSE: The present study presents the experience at the University of Florida
      with synchronous and metachronous squamous cell carcinomas of the head and neck
      mucosal sites. PATIENTS AND METHODS: This study included 1,112 patients with
      squamous cell carcinomas of the oropharynx, hypopharynx, and supraglottic larynx
      treated with radiation therapy with curative intent from 1964 to 1997. All
      patients had follow-up for at least 2 years. No patients were lost to follow-up.
      RESULTS: The overall survival rate was 45% and the disease-specific survival rate
      was 67% at 5 years after initial diagnosis of carcinoma of the head and neck
      mucosal sites. Seventy-seven patients (7%) presented with synchronous carcinomas
      of the head and neck mucosal sites and 103 patients (9%) developed metachronous
      carcinomas of the head and neck mucosal sites at 0.6 to 21.7 years (median, 3.6
      years). The overall survival rate was 31%, and the disease-specific survival rate
      was 50% at 5 years after metachronous carcinomas of the head and neck mucosal
      sites. Seven patients (1%) developed metachronous carcinomas of the thoracic
      esophagus at 1 to 11.1 years (median, 2.8 years), 15 patients (1%) presented with
      synchronous carcinomas of the lung, and 83 patients (7%) developed metachronous
      carcinomas of the lung at 0.6 to 17.6 years (median, 3.5 years). CONCLUSION:
      Development of synchronous and metachronous squamous cell carcinomas of the head
      and neck mucosal sites are in part responsible for failure to improve overall
      survival rates for patients with squamous cell carcinomas of the head and neck
      mucosal sites, justifying rigorous follow-up and studies on chemoprevention.

PMID- 11230480
TI  - Phase I study of paclitaxel given by seven-week continuous infusion concurrent
      with radiation therapy for locally advanced squamous cell carcinoma of the head
      and neck.
AB  - PURPOSE: Paclitaxel is one of the most active agents for squamous cell carcinoma
      of the head and neck (SCCHN) and an in vitro radiosensitizer. The dose-response
      relationship for paclitaxel may depend more on exposure duration than on peak
      concentration. This National Cancer Institute-sponsored phase I trial was
      designed to determine the feasibility of combining continuous-infusion (CI)
      paclitaxel with concurrent radiation therapy (RT). PATIENTS AND METHODS: Patients
      with previously untreated stage IVA/B SCCHN were eligible. Primary end points
      were determination of the maximum-tolerated dose, dose-limiting toxicity, and
      pharmacokinetics for paclitaxel given by CI (24 hours a day, 7 days a week for 7
      weeks) during RT (70 Gy/7 weeks). RESULTS: Twenty-seven patients were enrolled
      and assessable for toxicity. Nineteen of the patients who completed > or = 70 Gy
      were assessable for response. Grade 3 skin and mucosal acute reactions occurred
      at 10.5 mg/m(2)/d, but uninterrupted treatment was possible in five of six
      patients. At 17 mg/m(2)/d, skin toxicity required a 2-week treatment break for
      all three patients. The mean paclitaxel serum concentration at dose levels > or =
      6.5 mg/m(2)/d exceeded that reported to achieve in vitro radiosensitization.
      Initial locoregional control was achieved in 14 (58%) of 24 of patients treated
      to 70 Gy, and control persisted in nine (38%). CONCLUSION: CI paclitaxel with
      concurrent RT is a feasible and tolerable regimen for patients with advanced
      SCCHN and good performance status. Preliminary response and survival data are
      encouraging and suggest that further study is indicated. The recommended phase II
      dose of paclitaxel by CI is 10.5 mg/m(2)/d with RT for SCCHN.

PMID- 11230481
TI  - Estimation of risk of inherited medullary thyroid carcinoma in apparent sporadic
      patients.
AB  - PURPOSE: The study was undertaken to evaluate the frequency of inherited
      medullary thyroid carcinoma (MTC) among patients with apparent sporadic disease.
      A stepwise algorithm was used depending on clinical indices and the age of
      patient at MTC diagnosis. PATIENTS AND METHODS: One hundred sixteen patients with
      MTC verified by postoperative pathologic examination were subjected to genetic
      analysis of RET exons 10, 11, 13, 14, and 16 by means of polymerase chain
      reaction, restriction endonuclease digestion, and DNA sequencing. RESULTS: Among
      116 apparent sporadic MTC patients, we identified eleven (9.5%) RET germline
      mutation carriers. Seven of these (6.0%) were found by routine analysis (exons 10
      and 11). The frequency of inherited disease among patients younger than 45 years
      at diagnosis was 10.2% by analysis of typical mutations in exons 10 and 11.
      Extended genetic analysis (sequencing of exons 11, 13, 14, and 16) yielded 6.1%
      additional diagnoses, giving a risk of 16.3% in this age group. One previously
      unreported mutation in exon 11 affected codon 649 (TCG>TTG, Ser>Leu). In the true
      sporadic MTC patients younger than 30 years at diagnosis, frequencies of 36% and
      4.5% in polymorphic variants L769L and S836S, respectively, were observed. The
      frequency for L769L was higher than in older patients (P <.05). CONCLUSION: The
      frequency of inherited disease among apparent sporadic medullary thyroid
      carcinoma patients is close to 10% in the Polish population of MTC patients. The
      extended analysis of all known RET proto-oncogene mutation sites is obligatory in
      patients younger than 45 years at diagnosis, but we also see the need to analyze
      the impact of rarer mutations in older patients.

PMID- 11230482
TI  - Reproductive factors and risk of intermediate- or high-grade B-Cell non-Hodgkin's
      lymphoma in women.
AB  - PURPOSE: The incidence rates of non-Hodgkin's lymphoma (NHL) unrelated to human
      immunodeficiency virus infection are lower for women than for men; yet, few
      factors have been identified that may account for this difference in risk. NHL is
      difficult to study epidemiologically because this disorder represents a group of
      malignancies that differ in terms of morphologic presentation, immunologic
      features, genetic characteristics, prognosis, and etiology. PATIENTS AND METHODS:
      We conducted a population-based case-control study in women to determine whether
      reproductive factors or hormonal exposures might be related to the risk of high-
      or intermediate-grade B-cell NHL. We interviewed 177 female residents of Los
      Angeles County who were diagnosed with high- or intermediate-grade B-cell NHL
      between 1989 and 1992; each case patient was individually matched on age and race
      to a control subject who lived in her neighborhood. RESULTS: Women who had used
      oral contraceptives had significantly lower risk of intermediate- or high-grade
      NHL (multivariate odds ratio [OR] = 0.47; 95% confidence interval [CI], 0.26 to
      0.86) than women who had never used these compounds. Among parous women, those
      who had used lactation suppressants (which contain high levels of estrogen) had
      significantly lower risk of NHL (multivariate OR = 0.50; 95% CI, 0.29 to 0.85)
      than unexposed women. Postmenopausal women had a somewhat greater risk of NHL
      than premenopausal women, whereas those postmenopausal women who had used hormone
      replacement therapy (HRT) (primarily estrogen) had somewhat lower risk than those
      who had not used HRT. CONCLUSION: Exogenous estrogens seem to have a protective
      effect on the risk of high- and intermediate-grade B-cell NHL. Although the
      mechanisms for such protection are not known, alterations in immune reactivity,
      cytokine expression, or B-cell modulation may play a role.

PMID- 11230483
TI  - Image-aided estimate of tumor burden in Hodgkin's disease: evidence of its
      primary prognostic importance.
AB  - PURPOSE: To explore a more direct method for evaluating tumor burden (TB) in
      Hodgkin's disease (HD) and to verify its prognostic importance. PATIENTS AND
      METHODS: The volume of TB at diagnosis was directly and retrospectively measured
      in 121 HD patients through images of the lesions recorded by computed tomographic
      (CT) scan of the thorax, abdomen, and pelvis for all deep sites of involvement
      and many superficial ones, and by ultrasonography (US) for the remaining
      superficial lesions. RESULTS: The TB, which was obtained from the sum of the
      volumes of all the lesions measured on CT scans and US and normalized to body
      surface area (relative TB [rTB]), showed a median value of 102.6 cm(3)/m(2)
      (range, 2.2 to 582.8). At multivariate analysis for prognostic value, rTB was the
      parameter that statistically correlated best with time to treatment failure (P =
      2.2 x 10(-6)), followed by erythrocyte sedimentation rate (ESR) (P =.0003), and
      serum fibrinogen (P =.0112). The prognostic discrimination allowed by rTB alone
      proved to be clearly superior to that obtained with the score of the
      International Prognostic Factor Project. The rTB was found to be correlated with
      many clinical staging parameters (bulky disease, number of involved lymph node
      regions, serum lactate dehydrogenase, ESR, hemoglobin, Karnofsky index), but its
      predictability from these variables was low (R(2) =.668). CONCLUSION: Relative TB
      is emerging as a strong prognostic factor in HD, more powerful than and largely
      independent of those hitherto known and used. Further studies are needed to
      confirm these results and exploit their clinical value, particularly the
      relationship among rTB, drug doses, and response.

PMID- 11230484
TI  - Autologous stem-cell transplantation for Hodgkin's disease: results and
      prognostic factors in 494 patients from the Grupo Espanol de Linfomas/Transplante
      Autologo de Medula Osea Spanish Cooperative Group.
AB  - PURPOSE: To analyze clinical outcome and significant prognostic factors for
      overall (OS) and time to treatment failure (TTF) in a group of 494 patients with
      Hodgkin's disease (HD) undergoing autologous stem-cell transplantation (ASCT).
      PATIENTS AND METHODS: Detailed records from the Grupo Espanol de
      Linfomas/Transplante Autologo de Medula Osea Spanish Cooperative Group Database
      on 494 HD patients who received an ASCT between January 1984 and May 1998 were
      reviewed. Two hundred ninety-eight males and 196 females with a median age of 27
      years (range, 1 to 63 years) received autografts while in complete remission (n =
      203) or when they had sensitive disease (n = 206) or resistant disease (n = 75)
      at a median time of 26 months (range, 4 to 259 months) after diagnosis. Most
      patients received high-dose chemotherapy without radiation for conditioning (n =
      443). The graft consisted of bone marrow (n = 244) or peripheral blood (n = 250).
      RESULTS: The 100-day mortality rate was 9%. The 5-year actuarial TTF and OS rates
      were 45.0% (95% confidence interval [CI], 39.5% to 50.5%) and 54.5% (95% CI,
      48.4% to 60.6%), respectively. In multivariate analysis, the presence of active
      disease at transplantation, transplantation before 1992, and two or more lines of
      therapy before transplantation were adverse prognostic factors for outcome.
      Sixteen patients developed a secondary malignancy (5-year cumulative incidence of
      4.3%) after transplantation. Adjuvant radiotherapy before transplantation, the
      use of total-body irradiation (TBI) in the conditioning regimen, and age > or =
      40 years were found to be predictive factors for the development of second
      cancers after ASCT. CONCLUSION: ASCT achieves long-term disease-free survival in
      HD patients. Disease status before ASCT is the most important prognostic factor
      for final outcome; thus, transplantation should be considered in early stages of
      the disease. TBI must be avoided in the conditioning regimen because of a
      significantly higher rate of late complications, including secondary
      malignancies.

PMID- 11230485
TI  - Mutations with loss of heterozygosity of p53 are common in therapy-related
      myelodysplasia and acute myeloid leukemia after exposure to alkylating agents and
      significantly associated with deletion or loss of 5q, a complex karyotype, and a
      poor prognosis.
AB  - PURPOSE: To study mutations and loss of heterozygosity (LOH) of p53 in therapy
      related myelodysplasia (t-MDS) and acute myeloid leukemia (t-AML). PATIENTS AND
      METHODS: Fifty-two unselected patients with t-MDS and 25 patients with t-AML were
      studied by polymerase chain reaction (PCR)-single-strand conformational
      polymorphism (SSCP) at the DNA level and by reverse transcriptase (RT)-PCR-SSCP
      at the mRNA level, and cases with aberrant SSCP patterns were sequenced. RESULTS:
      Somatically acquired mutations of p53 were observed in 21 of 77 cases of t-MDS or
      t-AML, and 19 of these 21 patients had received alkylating agents. Single-base
      substitutions at A:T pairs were more common in t-MDS and t-AML, whereas single
      base substitutions at G:C pairs are most common in MDS and AML de novo and in
      solid tumors. Six patients demonstrated a cytogenetic loss of 17p13, and these
      six and an additional nine patients with p53 mutations demonstrated LOH of p53 at
      the DNA or mRNA level. This suggests a cytogenetic loss of the normal p53 allele
      in these nine cases combined with duplication of the homologous chromosome 17
      carrying the mutated p53 allele. Mutations of p53 were significantly associated
      with deletion or loss of 5q (P <.0001) and a complex karyotype (P =.0001), but
      surprisingly were not associated with deletion or loss of 7q (P =.73), and were
      infrequent in patients with balanced chromosome translocations (P =.03).
      Mutations of p53 were more common in older patients (P =.036) and were associated
      with an extremely poor prognosis (P =.014), apparently restricted to the 15 cases
      with LOH of p53 ( P =.046). CONCLUSION: Mutations with loss of function of p53
      are significantly associated with deletion or loss of 5q in t-MDS and t-AML after
      previous treatment with alkylating agents and are associated with genetic
      instability.

PMID- 11230486
TI  - Results of the fludarabine and cyclophosphamide combination regimen in chronic
      lymphocytic leukemia.
AB  - PURPOSE: To assess the efficacy of combination therapy with fludarabine and
      cyclophosphamide in patients with chronic lymphocytic leukemia (CLL) based on
      data suggesting in vitro synergistic activity of the two agents. PATIENTS AND
      METHODS: A total of 128 patients with CLL were treated with fludarabine 30
      mg/m(2) intravenously daily for 3 days and cyclophosphamide at either 500 mg/m(2)
      daily for 3 days (n = 11), 350 mg/m(2)/d for 3 days (n = 26), or 300 mg/m(2)
      daily for 3 days (n = 91). The cyclophosphamide dose was decreased because of
      myelosuppression in the early part of the study. Patients were divided into four
      groups based on the expectation for response to single-agent fludarabine,
      including previously untreated patients, patients previously treated with
      alkylating agents, patients successfully treated with alkylating agents and
      fludarabine but relapsing, and patients refractory to fludarabine with or without
      alkylating agents. RESULTS: Fludarabine and cyclophosphamide produced > or = 80%
      response rates in all patients not refractory to fludarabine at the start of
      therapy as well as a 38% response rate in patients who were refractory to
      fludarabine. The complete remission (CR) rate was 35% in previously untreated
      patients, which was not significantly different from the CR rate in historical
      control patients treated with single-agent fludarabine. However, residual disease
      assessed by flow cytometry occurred in only 8% of previously untreated patients
      achieving CR, and median time to progression has not been reached after a median
      follow-up of 41 months. The main complication of therapy was related to
      myelosuppression and infection. Neutropenia to less than 500 x 10(9)/L was noted
      in 48% of patients who received cyclophosphamide 300 mg/m(2). Pneumonia or sepsis
      occurred in 25% of patients, and fever of unknown origin occurred in another 25%.
      Pneumonia or sepsis were significantly more frequent in patients who were
      refractory to fludarabine at the start of combination chemotherapy. CONCLUSION:
      Fludarabine and cyclophosphamide seem to have a significant advantage over single
      agent fludarabine in the salvage setting. Although the CR rate was not increased
      in previously untreated patients, residual disease detected by flow cytometry was
      rare and remission durations seemed to be prolonged in this subset.
      Myelosuppression and infection remain the most significant complications of
      therapy in CLL.

PMID- 11230487
TI  - Pharmacokinetic evaluation of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide in
      patients by positron emission tomography.
AB  - PURPOSE: To evaluate tumor, normal tissue, and plasma pharmacokinetics of N-[2
      (dimethylamino)ethyl]acridine-4-carboxamide (DACA). The study aimed to determine
      the pharmacokinetics of carbon-11-labeled DACA ([11C]DACA) and evaluate the
      effect of pharmacologic doses of DACA on radiotracer kinetics. PATIENTS AND
      METHODS: [11C]DACA (at 1/1,000 phase I starting dose) was administered to 24
      patients with advanced cancer (pre-phase I) or during a phase I trial of DACA in
      five patients. Positron emission tomography (PET) was performed to assess
      pharmacokinetics and tumor blood flow. Plasma samples were analyzed for
      metabolite profile of [11C]DACA. RESULTS: There was rapid systemic clearance of
      [11C]DACA over 60 minutes (1.57 and 1.46 L x min(-1) x m(-2) in pre-phase I and
      phase I studies, respectively) with the production of several radiolabeled plasma
      metabolites. Tumor, brain, myocardium, vertebra, spleen, liver, lung, and kidneys
      showed appreciable uptake of 11C radioactivity. The area under the time-versus
      radioactivity curves (AUC) showed the highest variability in tumors. Of interest
      to potential toxicity, maximum radiotracer concentrations (Cmax) in brain and
      vertebra were low (0.67 and 0.54 m(2) x mL(-1), respectively) compared with other
      tissues. A moderate but significant correlation was observed for tumor blood flow
      with AUC (r = 0.76; P =.02) and standardized uptake value (SUV) at 55 minutes (r
      = 0.79; P =.01). A decrease in myocardial AUC ( P =.03) and splenic and
      myocardial SUV ( P =.01 and.004, respectively) was seen in phase I studies.
      Significantly higher AUC, SUV, and Cmax were observed in tumors in phase I
      studies. CONCLUSION: The distribution of [11C]DACA and its radiolabeled
      metabolites was observed in a variety of tumors and normal tissues. In the
      presence of unlabeled DACA, pharmacokinetics were altered in myocardium, spleen,
      and tumors. These data have implications for predicting activity and toxicity of
      DACA and support the use of PET early in drug development.

PMID- 11230488
TI  - High-dose interferon alfa-2b does not diminish antibody response to GM2
      vaccination in patients with resected melanoma: results of the Multicenter
      Eastern Cooperative Oncology Group Phase II Trial E2696.
AB  - PURPOSE: High-dose interferon alfa-2b (IFNalpha2b) is the only established
      adjuvant therapy of resectable high-risk melanoma. GM2-KLH/QS-21 (GMK) is a
      chemically defined vaccine that is one of the best developed of a range of
      vaccine candidates for melanoma. A single-institution phase III trial conducted
      at Memorial Hospital served as the impetus for an intergroup adjuvant
      E1694/S9512/C509801 trial, which recently completed enrollment of 880 patients.
      To build on the apparent benefit of IFNalpha2b in resectable high-risk American
      Joint Committee on Cancer (AJCC) stage IIB or III melanoma, this phase II study
      was designed to evaluate the combination of GMK and IFNalpha2b. The E2696 trial
      was undertaken to evaluate the toxicity and other effects of the established
      adjuvant high-dose IFNalpha2b regimen in relation to immune responses to GMK and
      to evaluate the potential clinical and immunologic effects of the combined
      therapies. PATIENTS AND METHODS: This trial enrolled 107 patients with resectable
      high- or very high-risk melanoma (AJCC stages IIB, III, and IV). RESULTS: The
      results demonstrate that IFNalpha2b does not significantly inhibit immunoglobulin
      M or G serologic responses to the vaccine and that the combination of high-dose
      IFNalpha2b and GMK is well tolerated in this patient population. CONCLUSION: Cox
      analysis of the results of the combination with IFNalpha2b show improvement in
      the relapse-free survival of patients with very high-risk melanoma (including
      those with resectable M1 disease).

PMID- 11230489
TI  - Detection of occult melanoma cells in paraffin-embedded histologically negative
      sentinel lymph nodes using a reverse transcriptase polymerase chain reaction
      assay.
AB  - PURPOSE: Detection of occult metastasis before the development of clinical
      disease could allow more accurate staging, appropriate follow-up procedures, and
      adjuvant therapies in patients with malignant melanoma (MM). The sentinel lymph
      node (SLN) has been proposed as a reliable predictor of metastatic disease in the
      lymphatic basin draining the primary melanoma. In this study, we screened both
      paraffin-embedded SLNs and peripheral-blood (PB) samples from MM patients at
      various stage of disease using a multimarker reverse transcriptase polymerase
      chain reaction (RT-PCR) assay. The prognostic significance of the presence of PCR
      positive markers was also evaluated. PATIENTS AND METHODS: Total RNA was obtained
      from paraffin-embedded SLN sections and PB samples of 75 MM patients. RT-PCR was
      performed using tyrosinase and MelanA/MART1 as melanoma-associated markers.
      Radiolabeled PCR products were analyzed on denaturing polyacrylamide gels.
      RESULTS: Good sensitivity of the RT-PCR assay on archival tissues was
      demonstrated after comparison of RT-PCR results on frozen and paraffin-embedded
      SLNs from 16 MM patients. Significant correlation between the disease stage and
      marker expression in both PB and SLN samples was observed; the highest value was
      for patients who were positive for both markers in SLN (P =.006). Progression of
      disease was significantly associated with the total number of PCR-positive
      markers in both PB (P =.034) and SLN (P =.001) samples. CONCLUSION: Although
      sensitivity is lowered by the use of paraffin-embedded specimens, our data
      indicate that RT-PCR analysis of serial sections from archival SLNs may be
      helpful in improving detection of occult micrometastases, thus improving staging
      of patients with melanoma.

PMID- 11230490
TI  - Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated
      doxorubicin and cyclophosphamide compared with conventional doxorubicin and
      cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer.
AB  - PURPOSE: To determine whether Myocet (liposome-encapsulated doxorubicin; The
      Liposome Company, Elan Corporation, Princeton, NJ) in combination with
      cyclophosphamide significantly reduces doxorubicin cardiotoxicity while providing
      comparable antitumor efficacy in first-line treatment of metastatic breast cancer
      (MBC). PATIENTS AND METHODS: Two hundred ninety-seven patients with MBC and no
      prior chemotherapy for metastatic disease were randomized to receive either 60
      mg/m(2) of Myocet (M) or conventional doxorubicin (A), in combination with 600
      mg/m(2) of cyclophosphamide (C), every 3 weeks until disease progression or
      unacceptable toxicity. Cardiotoxicity was defined by reductions in left
      ventricular ejection fraction, assessed by serial multigated radionuclide
      angiography scans, or congestive heart failure (CHF). Antitumor efficacy was
      assessed by objective tumor response rates (World Health Organization criteria),
      time to progression, and survival. RESULTS: Six percent of MC patients versus 21%
      (including five cases of CHF) of AC patients developed cardiotoxicity (P =.0002).
      Median cumulative doxorubicin dose at onset was more than 2,220 mg/m(2) for MC
      versus 480 mg/m(2) for AC (P =.0001, hazard ratio, 5.04). MC patients also
      experienced less grade 4 neutropenia. Antitumor efficacy of MC versus AC was
      comparable: objective response rates, 43% versus 43%; median time to progression,
      5.1% versus 5.5 months; median time to treatment failure, 4.6 versus 4.4 months;
      and median survival, 19 versus 16 months. CONCLUSION: Myocet improves the
      therapeutic index of doxorubicin by significantly reducing cardiotoxicity and
      grade 4 neutropenia and provides comparable antitumor efficacy, when used in
      combination with cyclophosphamide as first-line therapy for MBC.

PMID- 11230491
TI  - Patterns of use of chemotherapy for breast cancer in older women: findings from
      Medicare claims data.
AB  - PURPOSE: There is little population-based information available on the use of
      chemotherapy in women with breast cancer. This study describes the use of
      chemotherapy through analysis of Medicare claims and determines the correlates of
      chemotherapy use. PATIENTS AND METHODS: We used the merged Surveillance,
      Epidemiology, and End Results-Medicare database and identified women > or = 65
      years of age diagnosed with breast cancer in 1991 and 1992. Chemotherapy was
      ascertained from Medicare claims through procedure codes for chemotherapy made
      within 24 months of the diagnosis. RESULTS: In women with stages I, II, III, and
      IV breast cancer, the percentage receiving chemotherapy within 24 months of
      diagnosis was 5.1%, 19.5%, 33.9%, and 35.2%, respectively. Most women receiving
      chemotherapy had two to 12 claims; the median number was eight. Use of
      chemotherapy decreased significantly with age across all tumor stages; eg, in
      women with stage III cancer, the use of chemotherapy declined from 49% in those
      aged 65 to 69 years to 10% in those > or = 80 years old. In a multivariate
      analysis, there was little variation by ethnicity. Chemotherapy use was highest
      (70%) in women aged 65 to 69 years with node-positive and estrogen receptor
      negative tumors and lowest (5%) in those with node-negative and estrogen receptor
      positive tumors. Compared with those without comorbid diseases, patients with a
      comorbidity score of 2 had significantly lower use of chemotherapy. CONCLUSION:
      Medicare claims data seem to provide valuable information on the use of
      chemotherapy for breast cancer in older women. However, external validation of
      the accuracy and completeness of these data is required before any firm
      conclusion can be drawn.

PMID- 11230492
TI  - Nipple fluid carcinoembryonic antigen and prostate-specific antigen in cancer
      bearing and tumor-free breasts.
AB  - PURPOSE: Mammograms and breast examinations are established methods for early
      breast cancer detection. Routine mammography screening reduces breast cancer
      mortality among women ages > or = 50 years, but additional screening methods are
      needed. We and others have found high levels of carcinoembryonic antigen (CEA)
      and prostate-specific antigen (PSA) in nipple aspirate fluids (NAFs), but the
      usefulness for these bio-markers for early breast cancer detection is unknown.
      PATIENTS AND METHODS: NAFs from one or both breasts of 388 women were analyzed
      for CEA, PSA, and albumin levels. The study included 44 women with newly
      diagnosed invasive breast cancers, 67 women with proliferative breast lesions
      (ductal and lobular carcinoma in situ and atypical ductal hyperplasia), and 277
      controls without these breast lesions. Analyses were conducted using the log(10)
      transformed CEA and PSA levels to normalize the distributions of these tumor
      markers. RESULTS: Nipple fluid CEAs are significantly higher for cancerous
      breasts than tumor-free breasts (median 1,830 and 1,400 ng/mL, respectively; P
      <.01). However, at 90% specificity of the assay (CEA = 11,750 ng/mL), the
      corresponding sensitivity for cancer detection is 32%. CEA levels are not
      significantly different for breasts with proliferative lesions compared with
      tumor-free breasts. Nipple fluid PSAs do not differ by tumor status. Analyses of
      NAF albumin-standardized CEAs and PSAs yield similar results. Nipple fluid CEA
      and PSA titers are correlated in the affected and unaffected breast of women with
      unilateral lesions. CONCLUSION: Nipple fluid CEAs are higher for breasts with
      untreated invasive cancers, but the test sensitivity is low. Nipple fluid PSA
      titers do not seem to be useful for breast cancer detection.

PMID- 11230493
TI  - Comparative analysis of micrometastasis to the bone marrow and lymph nodes of
      node-negative breast cancer patients receiving no adjuvant therapy.
AB  - PURPOSE: In node-negative patients, of whom up to 30% will recur within 5 years
      after diagnosis, markers are still needed that identify patients at high enough
      risk to warrant further adjuvant treatment. In the present study we analyzed
      whether a correlation exists between microscopic tumor cell spread to bone marrow
      and to lymph nodes and attempted to determine which route is clinically more
      important. PATIENTS AND METHODS: According to a prospective design, bone marrow
      aspirates and axillary lymph nodes of level I (n = 1,590) from 150 node-negative
      patients with stage I or II breast cancer were analyzed immunocytochemically with
      monoclonal anticytokeratin (CK) antibodies. We investigated associations with
      prognostic factors and the effect of micrometastasis on patients' prognosis.
      RESULTS: CK-positive cells in bone marrow aspirates were present in 44 (29%) of
      150 breast cancer patients, whereas only 13 patients (9%) had such positive
      findings in lymph nodes; simultaneous microdissemination to bone marrow and lymph
      nodes was seen in merely two patients. No correlation of bone marrow
      micrometastases with other risk factors was assessed. Reduced 4-year distant
      disease-free and overall survival were each associated with a positive bone
      marrow finding (P =.032 and P =.014, respectively) but not with lymph node
      micrometastasis. Multivariate analysis revealed an independent prognostic effect
      of bone marrow micrometastasis on survival, with a hazards ratio of 6.1 (95%
      confidence interval, 1.2 to 31.3) for cancer-related death (P =.031) in our
      series. CONCLUSION: Immunocytochemical detection of micrometastatic cells in bone
      marrow but not in lymph nodes is an independent prognostic risk factor in node
      negative breast cancer that may have implications for surgery and stratification
      into adjuvant therapy trials.

PMID- 11230494
TI  - Phase I study of ZD9331 on short daily intravenous bolus infusion for 5 days
      every 3 weeks with fixed dosing recommendations.
AB  - PURPOSE: To conduct a phase I study of ZD9331, a potent, nonpolyglutamatable
      thymidylate synthase inhibitor using a short daily infusion for 5 consecutive
      days every 21 days. PATIENTS AND METHODS: Patients with refractory cancer or
      cancer for which no standard therapy was available were treated in escalating
      doses using an accelerated titration design. Plasma and urine samples were
      collected at timed intervals in the first cycle for pharmacokinetic analysis.
      RESULTS: Seventy-four patients were enrolled at 12 dose levels from a starting
      dose of 0.4 mg/m(2)/d to 16 mg/m(2)/d and 25 mg/d fixed dosing, of which 67 were
      assessable for toxicity. Maximum-tolerated dose was reached at 16 mg/m(2)/d.
      Myelosuppression was dose-limiting, consisting of thrombocytopenia associated
      with neutropenic fever. Body-surface area did not correlate with drug clearance;
      therefore, fixed daily dosing of 25 mg/d was studied and found to be tolerable,
      with two of 12 dose-limiting events. Dose-limiting nonhematologic toxicity
      consisted of grade 3 erythematous maculopapular rash observed in one patient at
      12 mg/m(2)/d and one patient at 25 mg/d. Pharmacokinetic analysis showed
      nonlinearity, with clearance increasing with dose. The mean clearance and
      terminal half-life of the drug were 6.6 +/- 2.0 mL/min and 71.3 +/- 27.0 hours,
      respectively. Area-under-the concentration-time curve was a better predictor of
      toxicity than dose, using multiple linear regression analyses. Minor response
      (40% shrinkage of tumor) was observed in one patient with colorectal cancer
      treated at 12 mg/m(2)/d. CONCLUSION: The recommended dose for ZD9331 on this
      schedule is 25 mg/d. Neutropenia, thrombocytopenia, and rash were dose-limiting,
      and efficacy studies in colorectal cancer are indicated.

PMID- 11230495
TI  - Phase I and pharmacokinetic study of PKC412, an inhibitor of protein kinase C.
AB  - PURPOSE: N-Benzoyl staurosporine (PKC412) is a protein kinase C inhibitor with
      antitumor activity in laboratory models. We determined the toxicity of oral
      PKC412 administered daily for repeat cycles of 28 days. PATIENTS AND METHODS:
      Thirty-two patients with advanced solid cancers were treated at seven dose levels
      (12.5 to 300 mg daily) for a total of 68 cycles. RESULTS: The most frequent
      treatment-related toxicities were nausea, vomiting, fatigue, and diarrhea. At the
      two top dose levels (225 and 300 mg/d), 15 of 16 patients experienced
      nausea/vomiting (common toxicity criteria [CTC], version 1), grade 2 in nine of
      16 and grade 3 in three of 16 patients; and six of 16 patients developed CTC
      grade 2 diarrhea. After 1 month of treatment, there were significant reductions
      in circulating lymphocyte (P <.02) and monocyte (P <.01) counts in patients
      receiving doses > or = 100 mg/d. Nevertheless, only two patients developed
      myelosuppression (both grade 2). Of two patients with progressive
      cholangiocarcinoma, one attained stable disease lasting 4.5 months and one a
      partial response lasting 4 months. There was a linear relationship between PKC412
      dose and area under the curve (0-24 hours) and maximum plasma concentration with
      marked interpatient variability. The estimated median elimination half-life was
      1.6 days (range, 0.9 to 4.0 days), and a metabolite with a median half-life of 36
      days was detected. Steady-state PKC412 plasma levels at the top three dose
      cohorts (150 to 300 mg) were five to 10 times the cellular 50% inhibitory
      concentration for PKC412 of 0.2 to 0.7 micromol/L. CONCLUSION: PKC412 can be
      safely administered by chronic oral therapy, and 150 mg/d is suitable for phase
      II studies. The pharmacokinetics and lack of conventional toxicity indicate that
      pharmacodynamic measures may be additionally needed to optimize the drug dose and
      schedule.

PMID- 11230496
TI  - Phase I and pharmacokinetic study of exatecan mesylate (DX-8951f): a novel
      camptothecin analog.
AB  - PURPOSE: To determine the maximum-tolerated dose (MTD), dose-limiting toxicity
      (DLT), pharmacokinetic (PK) profile, and recommended phase II dose of Exatecan
      mesylate (DX-8951f) when administered as a 24-hour continuous infusion every 3
      weeks to patients with solid tumors. PATIENTS AND METHODS: Twenty-two patients
      with advanced solid tumors, all previously treated, and with performance status <
      or = 2, were entered. The starting dose of DX-8951f was 0.15 mg/m(2); the dose
      was escalated according to the modified continual reassessment method. The drug
      was administered until disease progression or until unacceptable toxic effects
      occurred. RESULTS: Seven dose escalations were completed, and a total of 53
      courses were delivered (median, two courses; range, one to eight courses) during
      the study. At doses 1.2 mg/m(2) and lower, toxicities were mostly grade 1,
      primarily hematologic. In the initial cohort of three patients treated at 2.4
      mg/m(2), grade 2 hematologic toxicity was observed. Of the six additional
      patients entered at 2.4 mg/m(2), three had grade 3 or 4 granulocytopenia. At
      doses higher than 2.4 mg/m(2), DLT granulocytopenia was observed. Nonhematologic
      toxicities, including nausea, vomiting, diarrhea, fatigue, and alopecia, were
      mild to moderate. Neither complete nor partial responses were observed, but four
      patients had stable disease. The PK profile of DX-8951f seemed linear at the
      doses administered. The plasma clearance, total volume of distribution, and
      terminal elimination half-life were approximately 3 L/h, 40 L, and 14 hours,
      respectively. CONCLUSION: The DLT of this DX-8951f schedule was granulocytopenia
      for minimally pretreated patients, and both granulocytopenia and thrombocytopenia
      for heavily pretreated patients. The MTD for both minimally and heavily
      pretreated patients was 2.4 mg/m(2). DX-8951f seems to have a linear PK profile
      on the basis of single-dose administration. The recommended phase II dose with
      this schedule is 2.4 mg/m(2) for minimally pretreated patients. A lower dose
      should be used for heavily pretreated patients.

PMID- 11230497
TI  - Irinotecan in the treatment of colorectal cancer: clinical overview.
AB  - PURPOSE AND METHODS: For more than three decades, the therapeutic options for
      patients with advanced colorectal cancer have almost exclusively been based on
      fluoropyrimidines. With the recognition that topoisomerase-I (TOP-I) is an
      important therapeutic target in cancer therapy, irinotecan, a semisynthetic TOP-I
      interactive camptothecin derivative, has been clinically established in the
      treatment of colorectal cancer. RESULTS: Irinotecan was investigated as second
      line chemotherapy after prior treatment with fluorouracil (FU)-based regimens in
      two large randomized phase III trials comparing irinotecan with either best
      supportive care or an infusional FU/leucovorin (LV) regimen. The outcomes of
      these trials established irinotecan as the standard therapy in the second-line
      treatment of colorectal cancer. The therapeutic value of irinotecan in the first
      line treatment of metastatic colorectal cancer was investigated in two large
      randomized phase III trials comparing the combination of irinotecan and FU/LV
      with FU/LV alone. Both trials demonstrated significant superior efficacy for the
      combination of irinotecan and FU/LV in terms of response rate, median time to
      disease progression, and median survival time. Consequently, the combination of
      irinotecan and FU/LV has been approved as first-line chemotherapy for patients
      with metastatic colorectal cancer and constitutes the reference therapy against
      which other treatment options must be tested in the future. CONCLUSION: In this
      review, the clinical rationale and update of the present clinical status of
      irinotecan in the treatment of colorectal cancer and future prospects of
      irinotecan-based combinations are discussed.

PMID- 11230498
TI  - Platelet transfusion for patients with cancer: clinical practice guidelines of
      the American Society of Clinical Oncology.
AB  - OBJECTIVE: To determine the most effective, evidence-based approach to the use of
      platelet transfusions in patients with cancer. OUTCOMES: Outcomes of interest
      included prevention of morbidity and mortality from hemorrhage, effects on
      survival, quality of life, toxicity reduction, and cost-effectiveness. EVIDENCE:
      A complete MedLine search was performed of the past 20 years of the medical
      literature. Keywords included platelet transfusion, alloimmunization, hemorrhage,
      threshold and thrombocytopenia. The search was broadened by articles from the
      bibliographies of selected articles. VALUES: Levels of evidence and guideline
      grades were rated by a standard process. More weight was given to studies that
      tested a hypothesis directly related to one of the primary outcomes in a
      randomized design. BENEFITS/HARMS/COST: The possible consequences of different
      approaches to the use of platelet transfusion were considered in evaluating a
      preference for one or another technique producing similar outcomes. Cost alone
      was not a determining factor. RECOMMENDATIONS: Appendix A summarizes the
      recommendations concerning the choice of particular platelet preparations, the
      use of prophylactic platelet transfusions, indications for transfusion in
      selected clinical situations, and the diagnosis, prevention, and management of
      refractoriness to platelet transfusion. VALIDATION: Five outside reviewers, the
      ASCO Health Services Research Committee, and the ASCO Board reviewed this
      document. SPONSOR: American Society of Clinical Oncology

PMID- 11230499
TI  - Postmastectomy radiotherapy: clinical practice guidelines of the American Society
      of Clinical Oncology.
AB  - OBJECTIVE: To determine indications for the use of postmastectomy radiotherapy
      (PMRT) for patients with invasive breast cancer with involved axillary lymph
      nodes or locally advanced disease who receive systemic therapy. These guidelines
      are intended for use in the care of patients outside of clinical trials.
      POTENTIAL INTERVENTION: The benefits and risks of PMRT in such patients, as well
      as subgroups of these patients, were considered. The details of the PMRT
      technique were also evaluated. OUTCOMES: The outcomes considered included freedom
      from local-regional recurrence, survival (disease-free and overall), and long
      term toxicity. EVIDENCE: An expert multidisciplinary panel reviewed pertinent
      information from the published literature through July 2000; certain
      investigators were contacted for more recent and, in some cases, unpublished
      information. A computerized search was performed of MEDLINE data; directed
      searches based on the bibliographies of primary articles were also performed.
      VALUES: Levels of evidence and guideline grades were assigned by the Panel using
      standard criteria. A "recommendation" was made when level I or II evidence was
      available and there was consensus as to its meaning. A "suggestion" was made
      based on level III, IV, or V evidence and there was consensus as to its meaning.
      Areas of clinical importance were pointed out where guidelines could not be
      formulated due to insufficient evidence or lack of consensus. RECOMMENDATIONS:
      The recommendations, suggestions, and expert opinions of the Panel are described
      in this article. VALIDATION: Seven outside reviewers, the American Society of
      Clinical Oncology (ASCO) Health Services Research Committee members, and the ASCO
      Board of Directors reviewed this document.

PMID- 11230500
TI  - Unusual sites of malignancy: case 1. Primary non-Hodgkin's lymphoma of the hand
      in a patient with hepatitis C infection.

PMID- 11230501
TI  - Unusual sites of malignancy: case 2. Orbital lymphoma.

PMID- 11230502
TI  - Unusual sites of malignancy: case 3. Solitary splenic metastasis in lung cancer
      with spontaneous rupture.

PMID- 11230503
TI  - Discussing do-not-resuscitate status.

PMID- 11230504
TI  - Clarification on the potential of subcutaneous ethyol as a radioprotective agent.

PMID- 11230505
TI  - Patients aged > or = 70 are at high risk for neutropenic infection and should
      receive hemopoietic growth factors when treated with moderately toxic
      chemotherapy.

PMID- 11230506
TI  - Relationship of Ca2+ sparks to STOCs studied with 2D and 3D imaging in feline
      oesophageal smooth muscle cells.
AB  - We recorded Ca2+ sparks and spontaneous transient outward currents (STOCs)
      simultaneously in smooth muscle cells using whole-cell patch recording and a
      unique, high-speed widefield digital imaging system to monitor fluo-3
      fluorescence in both two and three dimensions (2D and 3D). In 2D imaging, the
      correlation between the amplitude of a spark and its corresponding STOC was a
      weak one, and 27 % of the sparks failed to cause STOCs. The STOCless sparks were
      not significantly different in amplitude from those that caused STOCs. Three
      dimensional imaging disclosed that STOCless sparks were located close to the cell
      surface, and on average their apparent distance from the cell surface was not
      significantly different from the sparks that cause STOCs. Statistical evaluation
      of spark clusters disclosed that there were regions of the cell where the
      probability of spark occurrence was high and others where it was quite low.

PMID- 11230507
TI  - Expression and permeation properties of the K(+) channel Kir7.1 in the retinal
      pigment epithelium.
AB  - Bovine Kir7.1 clones were obtained from a retinal pigment epithelium (RPE)
      subtracted cDNA library. Human RPE cDNA library screening resulted in clones
      encoding full-length human Kir7.1. Northern blot analysis indicated that bovine
      Kir7.1 is highly expressed in the RPE. Human Kir7.1 channels were expressed in
      Xenopus oocytes and studied using the two-electrode voltage-clamp technique. The
      macroscopic Kir7.1 conductance exhibited mild inward rectification and an inverse
      dependence on extracellular K+ concentration ([K+]o). The selectivity sequence
      based on permeability ratios was K+ (1.0) approximately Rb+ (0.89) > Cs+ (0.013)
      > Na+ (0.003) approximately Li+ (0.001) and the sequence based on conductance
      ratios was Rb+ (9.5) >> K+ (1.0) > Na+ (0.458) > Cs+ (0.331) > Li+ (0.139). Non
      stationary noise analysis of Rb+ currents in cell-attached patches yielded a
      unitary conductance for Kir7.1 of approximately 2 pS. In whole-cell recordings
      from freshly isolated bovine RPE cells, the predominant current was a mild
      inwardly rectifying K+ current that exhibited an inverse dependence of
      conductance on [K+]o. The selectivity sequence based on permeability ratios was
      K+ (1.0) approximately Rb+ (0.89) > Cs+ (0.021) > Na+ (0.003) approximately Li+
      (0.002) and the sequence based on conductance ratios was Rb+ (8.9) >> K+ (1.0) >
      Na+ (0.59) > Cs+ (0.23) > Li+ (0.08). In cell-attached recordings with Rb+ in the
      pipette, inwardly rectifying currents were observed in nine of 12 patches of RPE
      apical membrane but in only one of 13 basolateral membrane patches. Non
      stationary noise analysis of Rb+ currents in cell-attached apical membrane
      patches yielded a unitary conductance for RPE Kir of approximately 2 pS. On the
      basis of this molecular and electrophysiological evidence, we conclude that
      Kir7.1 channel subunits comprise the K+ conductance of the RPE apical membrane.

PMID- 11230508
TI  - Alternative splicing of KCNQ2 potassium channel transcripts contributes to the
      functional diversity of M-currents.
AB  - The region of alternative splicing in the KCNQ2 potassium channel gene was
      determined by RNase protection analysis of KCNQ2 mRNA transcripts. Systematic
      analysis of KCNQ2 alternative splice variant expression in rat superior cervical
      ganglia revealed multiple variant isoforms. One class of KCNQ2 splice variants,
      those that contained exon 15a, was found to have significantly different kinetics
      to those of the other isoforms. These transcripts encoded channel subunits that,
      when co-expressed with the KCNQ3 subunit, activated and deactivated approximately
      2.5 times more slowly than other isoforms. Deletion of exon 15a in these isoforms
      produced a reversion to the faster kinetics. Comparison of the kinetic properties
      of the cloned channel splice variants with those of the native M-current suggests
      that alternative splicing of the KCNQ2 gene may contribute to the variation in M
      current kinetics seen in vivo.

PMID- 11230509
TI  - K+ currents underlying the action of endothelium-derived hyperpolarizing factor
      in guinea-pig, rat and human blood vessels.
AB  - Membrane currents attributed to endothelium-derived hyperpolarizing factor (EDHF)
      were recorded in short segments of submucosal arterioles of guinea-pigs using
      single microelectrode voltage clamp. The functional responses of arterioles and
      human subcutaneous, rat hepatic and guinea-pig coronary arteries were also
      assessed as changes in membrane potential recorded simultaneously with
      contractile activity. The current-voltage (I-V) relationship for the conductance
      due to EDHF displayed outward rectification with little voltage dependence.
      Components of the current were blocked by charybdotoxin (30-60 nM) and apamin
      (0.25-0.50 microM), which also blocked hyperpolarization and prevented EDHF
      induced relaxation. The EDHF-induced current was insensitive to Ba2+ (20-100
      microM) and/or ouabain (1 microM to 1 mM). In human subcutaneous arteries and
      guinea-pig coronary arteries and submucosal arterioles, the EDHF-induced
      responses were insensitive to Ba2+ and/or ouabain. Increasing [K+]o to 11-21 mM
      evoked depolarization under conditions in which EDHF evoked hyperpolarization.
      Responses to ACh, sympathetic nerve stimulation and action potentials were
      indistinguishable between dye-labelled smooth muscle and endothelial cells in
      arterioles. Action potentials in identified endothelial cells were always
      associated with constriction of the arterioles. 18beta-Glycyrrhetinic acid (30
      microM) and carbenoxolone (100 microM) depolarized endothelial cells by 31 +/- 6
      mV (n = 7 animals) and 33 +/- 4 mV (n = 5), respectively, inhibited action
      potentials in smooth muscle and endothelial cells and reduced the ACh-induced
      hyperpolarization of endothelial cells by 56 and 58 %, respectively. Thus,
      activation of outwardly rectifying K+ channels underlies the hyperpolarization
      and relaxation due to EDHF. These channels have properties similar to those of
      intermediate conductance (IKCa) and small conductance (SKCa) Ca2+-activated K+
      channels. Strong electrical coupling between endothelial and smooth muscle cells
      implies that these two layers function as a single electrical syncytium. The non
      specific effects of glycyrrhetinic acid precludes its use as an indicator of the
      involvement of gap junctions in EDHF-attributed responses. These conclusions are
      likely to apply to a variety of blood vessels including those of humans.

PMID- 11230510
TI  - The stoichiometry of the electrogenic sodium bicarbonate cotransporter pNBC1 in
      mouse pancreatic duct cells is 2 HCO(3)(-):1 Na(+).
AB  - The electrogenic sodium bicarbonate cotransporter pNBC1 is believed to play a
      major role in the secretion of bicarbonate by pancreatic duct cells, by
      transporting bicarbonate into the cell across the basolateral membrane.
      Thermodynamics predict that this function can be achieved only if the reversal
      potential of the cotransporter is negative to the cell's membrane potential, or
      equivalently that the HCO3-:Na+ stoichiometry is not larger then 2:However, there
      are no data available on either the reversal potential or the HCO3-:Na+
      stoichiometry of pNBC1 in pancreatic cells. We studied pNBC1 function in mouse
      pancreatic duct cells. RT-PCR analysis of total RNA revealed that these cells
      contain the message for pNBC1, but not for kNBC1, NBC2 or NBC3. To measure
      cotransporter activity, mouse pancreatic duct cells were grown to confluence on a
      porous substrate, mounted in an Ussing chamber, and the apical plasma membrane
      permeabilized with amphotericin B. Ion flux through pNBC1 was achieved by
      applying Na+ concentration gradients across the basolateral plasma membrane. The
      current through the cotransporter was isolated as the difference current due to
      the reversible inhibitor dinitrostilbene disulfonate (DNDS). Current-voltage
      relationships for the cotransporter, measured at three different Na+
      concentration gradients, were linear over a range of about 100 mV. The reversal
      potential data, obtained from these current-voltage relationships, all
      corresponded to a 2 HCO3-:1 Na+ stoichiometry. The data indicate that pNBC1 is
      functionally expressed in mouse pancreatic duct cells. The cotransporter operates
      with a 2 HCO3-:1 Na+ stoichiometry in these cells, and mediates the transport of
      bicarbonate into the cell across the basolateral membrane.

PMID- 11230511
TI  - Amino acids involved in sodium interaction of murine type II Na(+)-P(i)
      cotransporters expressed in Xenopus oocytes.
AB  - Type IIa and IIb Na+-Pi cotransporters are highly conserved proteins expressed in
      brush border membranes of proximal tubules and small intestine, respectively. The
      kinetics of IIa and IIb differ significantly: type IIb is saturated at lower
      concentrations of Na+ and Pi. To define the domain responsible for the difference
      in Na+ affinity we constructed several mouse IIa-IIb chimeras as well as site
      directed mutagenized cotransporters. Pi uptake activity was determined after
      injection of cRNAs into Xenopus laevis oocytes. From the chimera experiments we
      concluded that the domain containing part of the second intracellular loop, the
      fifth transmembrane domain (TD) and part of the third extracellular loop
      determines the specific Na+ activation properties for both types of
      cotransporter. Within this domain only a few residues located in the fifth TD are
      not conserved between type IIa and IIb. Site-directed mutagenesis on non
      conserved residues was performed. Substitution of F402 of IIa by the
      corresponding L418 from IIb yielded a cotransporter that behaved like the IIb. On
      the other hand, substitution of the specific L418 of IIb by the corresponding
      F402 of IIa produced a cotransporter with a Na+ activation similar to IIa.
      (Single letter amino acid nomenclature is used throughout the paper.) These data
      suggest that the specific Na+ activation properties exhibited by type IIa and
      type IIb Na+-Pi cotransporters are at least in part due to the presence of a
      specific amino acid (F402 in IIa, and L418 in IIb) within the fifth TD of the
      protein.

PMID- 11230512
TI  - ATP utilization for calcium uptake and force production in different types of
      human skeletal muscle fibres.
AB  - The contractile properties and ATPase activity of skinned human skeletal muscle
      fibres from vastus lateralis were examined. Fibre types were resolved from single
      fibre segments by SDS-polyacrylamide gel electrophoresis. ATPase activity was
      determined by enzymatic coupling of ATP resynthesis to the oxidation of NADH. The
      partitioning of ATPase activity into (a) calcium-activated activity due to
      actomyosin (AM) interaction, (b) calcium-activated activity of the sarcoplasmic
      reticular (SR) calcium pump, and (c) basal (calcium independent) activity was
      investigated by comparing ATP utilization before and after exposure of the
      preparations for 30 min to a solution containing 0.5 % Triton X-100, which
      effectively abolished the SR ATPase activity. Partitioning of ATPase activity was
      also determined by measuring ATP utilization and force at different
      concentrations of butanedione monoxime (BDM), which inhibits AM interaction. The
      results obtained with Triton X-100 and BDM were similar. At saturating Ca2+
      concentrations and 20 degrees C, the AM, SR and basal ATPase activities per litre
      cell volume (+/- S.E.M.) amounted to 46 +/- 4, 51 +/- 4 and 19 +/- 2 muM s-1 in
      type I fibres (n = 21), 139 +/- 14, 69 +/- 8 and 30 +/- 3 muM s-1 in type IIA
      fibres (n = 25), 137 +/- 22, 175 +/- 28 and 26 +/- 8 muM s-1 in type IIA/B fibres
      (n = 4) and 108 +/- 13, 169 +/- 42 and 32 +/- 8 muM s-1 in type IIB fibres (n =
      2). These results indicate that ATP utilization for SR Ca2+ pumping in fast
      fibres is considerably larger than in slow fibres. The SR ATPase activity in
      human muscle represents a considerable fraction of the total (AM + SR + basal)
      ATPase activity.

PMID- 11230513
TI  - Characterisation of L-tryptophan transporters in human placenta: a comparison of
      brush border and basal membrane vesicles.
AB  - The mechanisms responsible for L-tryptophan transport at both the maternal- and
      fetal-facing surfaces of the term placenta have been determined in isolated
      membrane vesicles as part of a study on placental indoleamine 2,3-dioxygenase,
      the L-tryptophan-catabolising enzyme recently shown to regulate feto-maternal
      immunology. Brush border vesicle uptake of L-tryptophan is substantially into an
      osmotically active space. It is sodium independent and N-ethylmaleimide
      sensitive. Uptake of L-tryptophan, which is markedly stereospecific, has a Km of
      26.3 microM and Vmax of 1.72 pmol (mg protein)(-1) s(-1) and is completely
      abolished by the L-system-specific substrate 2-aminobicyclo-(2,2,1)-heptane-2
      carboxylic acid (BCH). These findings are in keeping with L-tryptophan transport
      being exclusively via system L (induced by the heterodimeric heavy chain of CD98
      and system L-amino acid transporter-1 (LAT-1)). 1-Methyl-tryptophan (which is a
      known competitive inhibitor of indoleamine 2,3-dioxygenase) is a competitive
      inhibitor of L-tryptophan flux through this transport system (Ki = 113 microM).
      Basal membrane transport of L-tryptophan is more complex. Uptake is slower than
      at the brush border and although, as in the brush border, uptake is sodium
      independent, it is less sensitive to N-ethylmaleimide. There is clear evidence
      that two systems contribute to basal membrane transport since BCH is (in sodium
      free media) only a partial inhibitor whereas L-histidine and L-cysteine are fully
      effective. The simplest explanation of these and other findings is that the basal
      membrane possesses two systems, one of which is similar to that induced by the
      heavy chain of CD98 and system L-amino acid transporter-2 (LAT-2). The other
      appears to be system y+L since in the presence of BCH inhibition by L-leucine but
      not by L-lysine is sodium dependent. These findings suggest the existence of non
      identical carrier-mediated transport systems for L-tryptophan in brush border and
      basal membranes. This asymmetry may explain net transplacental transfer of this
      amino acid.

PMID- 11230514
TI  - The role of L-tryptophan transport in L-tryptophan degradation by indoleamine 2,3
      dioxygenase in human placental explants.
AB  - The physiological importance of L-tryptophan transport for placental indoleamine
      2,3-dioxygenase-mediated degradation of L-tryptophan has been studied using human
      placental chorionic villous explants. L-Tryptophan influx into villous explants
      is supported exclusively by transport system L and is substantially inhibited by
      the L-system-specific substrate 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid
      (BCH) and also by 1-methyl-tryptophan which is also an inhibitor of indoleamine
      2,3-dioxygenase. L-Tryptophan influx is enhanced 2.3-fold following in vitro
      culture of the villous explant. Interferon-gamma, which increases villous explant
      indoleamine 2,3-dioxygenase expression, has no effect on L-tryptophan influx. In
      explants both BCH and 1-methyl-tryptophan inhibit indoleamine 2,3-dioxygenase
      mediated L-tryptophan degradation. This also applies when L-tryptophan
      degradation has been stimulated by interferon-gamma. These findings show
      transport of L-tryptophan into the trophoblast to be a rate-limiting step for
      indoleamine 2,3-dioxygenase-mediated L-tryptophan degradation and therefore for
      the normal physiology of mammalian pregnancy.

PMID- 11230515
TI  - The peptide TRH uncovers the presence of presynaptic 5-HT1A receptors via
      activation of a second messenger pathway in the rat dorsal vagal complex.
AB  - It is well recognized that brainstem microinjections of 5-hydroxytryptamine
      (serotonin, 5-HT) and thyrotropin-releasing hormone (TRH) act synergistically to
      stimulate gastric function in vivo. Previous in vitro experiments have shown that
      this synergism does not occur at the level of the dorsal motor nucleus of the
      vagus (DMV) motoneurone. In order to determine the mechanism of this action,
      whole cell patch clamp recordings were made from identified gastric-projecting
      rat DMV neurones to investigate the effects of 5-HT and TRH on GABAergic
      inhibitory postsynaptic currents (IPSCs) evoked by stimulation of the nucleus of
      the tractus solitarius (NTS). 5-HT (30 microM) decreased IPSC amplitude by 26 +/-
      2.5% in approximately 43% of DMV neurones. In the remaining neurones in which 5
      HT had no effect on IPSC amplitude, exposure to TRH (1 microM) uncovered the
      ability of subsequent applications of 5-HT to decrease IPSC amplitude by 28 +/-
      3%. Such TRH-induced 5-HT responses were prevented by the 5-HT1A antagonist NAN
      190 (1 microM) and mimicked by the 5-HT1A agonist 8-OH-DPAT (1 microM).
      Increasing cAMP levels using the phosphodiesterase inhibitor
      isobutylmethylxanthine (IBMX; 10 microM), the non-hydrolysable cAMP analogue 8
      bromo-cAMP (1 mM), or the adenylate cyclase activator forskolin (10 microM), like
      TRH, uncovered the ability of 5-HT to decrease evoked IPSC amplitude (17 +/- 2.2
      %, 28.5 +/- 5.3 % and 30 +/- 4.8%, respectively), in neurones previously
      unresponsive to 5-HT. Conversely, the adenylate cyclase inhibitor,
      dideoxyadenosine (10 microM) and the protein kinase A inhibitor, Rp-cAMP (10
      microM), blocked the ability of TRH to uncover the presynaptic inhibitory actions
      of 5-HT. These results suggest that activation of presynaptic TRH receptors
      initiates an intracellular signalling cascade that raises the levels of cAMP
      sufficient to uncover previously silent 5-HT1A receptors on presynaptic nerve
      terminals within the dorsal vagal complex.

PMID- 11230516
TI  - Functional inhibition of native volume-sensitive outwardly rectifying anion
      channels in muscle cells and Xenopus oocytes by anti-ClC-3 antibody.
AB  - Intracellular dialysis of NIH/3T3 cells with a commercially available anti-ClC-3
      polyclonal antibody (Ab) for approximately 30 min completely inhibited expressed
      guinea-pig ClC-3 currents (IgpClC-3), while intracellular dialysis with antigen
      preabsorbed anti-ClC-3 Ab failed to affect IgpClC-3. Anti-ClC-3 Ab was used as a
      selective probe to examine the relationship between endogenous ClC-3 expression
      and native volume-sensitive outwardly rectifying anion channels (VSOACs) in
      guinea-pig cardiac cells, canine pulmonary arterial smooth muscle cells (PASMCs)
      and Xenopus laevis oocytes. Intracellular dialysis or injection of anti-ClC-3 Ab
      abolished native VSOAC function in cardiac cells and PASMCs and significantly
      reduced VSOACs in oocytes. In contrast, native VSOAC function was unaltered by
      antigen-preabsorbed anti-ClC-3 Ab. It is suggested that endogenous ClC-3
      represents a major molecular entity responsible for native VSOACs in cardiac and
      smooth muscle cells and Xenopus oocytes. Anti-ClC-3 Ab should be a useful
      experimental tool to directly test the relationship between endogenous ClC-3
      expression and native VSOAC function, and help resolve existing controversies
      related to the regulation and physiological role of native VSOACs in a wide
      variety of different cells.

PMID- 11230517
TI  - Adenoviral vector demonstrates that angiotensin II-induced depression of the
      cardiac baroreflex is mediated by endothelial nitric oxide synthase in the
      nucleus tractus solitarii of the rat.
AB  - Angiotensin II (ANGII) acting on ANGII type 1 (AT1) receptors in the solitary
      tract nucleus (NTS) depresses the baroreflex. Since ANGII stimulates the release
      of nitric oxide (NO), we tested whether the ANGII-mediated depression of the
      baroreflex in the NTS depended on NO release. In a working heart-brainstem
      preparation (WHBP) of rat NTS microinjection of either ANGII (500 fmol) or a NO
      donor (diethylamine nonoate, 500 pmol) both depressed baroreflex gain by -56 and 
      67 %, respectively (P < 0.01). In contrast, whilst ANGII potentiated the
      peripheral chemoreflex, the NO donor was without effect. NTS microinjection of
      non-selective NO synthase (NOS) inhibitors (L-NAME; 50 pmol) or (L-NMMA; 200
      pmol) prevented the ANGII-induced baroreflex attenuation (P > 0.1). In contrast,
      a neurone-specific NOS inhibitor, TRIM (50 pmol), was without effect. Using an
      adenoviral vector, a dominant negative mutant of endothelial NOS (TeNOS) was
      expressed bilaterally in the NTS. Expression of TeNOS affected neither baseline
      cardiovascular parameters nor baroreflex sensitivity. However, ANGII
      microinjected into the transfected region failed to affect the
      baroreflex.Immunostaining revealed that eNOS-positive neurones were more numerous
      than those labelled for AT1 receptors. Neurones double labelled for both AT1
      receptors and eNOS comprised 23 +/- 5.4 % of the eNOS-positive cells and 57 +/-
      9.2 % of the AT1 receptor-positive cells. Endothelial cells were also double
      labelled for eNOS and AT1 receptors. We suggest that ANGII activates eNOS located
      in either neurones and/or endothelial cells to release NO, which acts selectively
      to depress the baroreflex.

PMID- 11230518
TI  - Neuroprotective role of monocarboxylate transport during glucose deprivation in
      slice cultures of rat hippocampus.
AB  - The effects of energy substrate removal and metabolic pathway block have been
      examined on neuronal and glial survival in organotypic slice cultures of rat
      hippocampus. Slice cultures resisted 24 h of exogenous energy substrate
      deprivation. Application of 0.5 mM alpha-cyano-4-hydroxycinnamate (4-CIN) for 24
      h resulted in specific damage to neuronal cell layers, which could be reversed by
      co-application of 5 mM lactate. Addition of 10 mM 2-deoxyglucose in the absence
      of exogenous energy supply produced widespread cell death throughout the slice.
      This was partly reversed by co-application of 5 mM lactate. These effects of
      metabolic blockade on cell survival were qualitatively similar to the effects on
      population spikes recorded in the CA1 cell layer following 60 min application of
      these agents. The data suggest that monocarboxylate trafficking from glia to
      neurons is an essential route for supply of energy substrates to neurons
      particularly when exogenous energy supply is restricted.

PMID- 11230520
TI  - Vesicle release probability and pre-primed pool at glutamatergic synapses in area
      CA1 of the rat neonatal hippocampus.
AB  - Factors determining the release probability were examined using whole-cell patch
      clamp recording and minimal stimulation (10 impulses, 50 Hz) of individual
      glutamatergic synapses, containing single release sites, on pyramidal neurones in
      the CA1 region of hippocampal slices from neonatal rats. Release probability
      following the first action potential in the burst (P1) varied among the synapses
      from 0 to 0.87 (mean +/- s.d.; 0.35 +/- 0.28, n = 52) and the average release
      during the burst (burst pool) varied from 0.4 to 4.1 events (1.7 +/- 0.85, n =
      52). Heterogeneity in P1 did not co-vary with that of the burst pool. By
      selecting burst trials during which only one release event occurred, the vesicle
      release probability (Pves) at a release site could be determined. It was found to
      vary considerably among the synapses, from 0.04 to 0.94 (0.43 +/- 0.28, n = 43).
      This heterogeneity correlated significantly with that of P1 such that more than
      half of the variation of P1 could be explained by a variation in Pves. The
      average number of vesicles directly available for release at the onset of the
      burst (the pre-primed pool) was estimated as the cumulative release up to that
      point in the burst where a second release event did not produce higher initial
      release probability than that found in trials where only one vesicle was
      released. The average pre-primed pool varied among the synapses from 0.4 to 2.1
      (1.03 +/- 0.42, n = 43). It co-varied significantly with that of P1 such that it
      could explain the remaining variation in P1. The difference between the burst
      pool and the pre-primed pool suggests the presence of a fast (< 100 ms), activity
      dependent priming of vesicles. Some synapses (9/52) did not show any initial
      release (P1 = 0), but release occurred later during the burst ('low frequency
      mute synapses'). Their behaviour was explained by an absence of a pre-primed
      pool.

PMID- 11230519
TI  - Quantal variability at glutamatergic synapses in area CA1 of the rat neonatal
      hippocampus.
AB  - Quantal variability was determined at glutamatergic synapses in the neonatal
      (postnatal days 1-7) rat hippocampal slice preparation. Synaptic AMPA and NMDA
      quantal EPSCs were recorded from CA1 pyramidal neurones using the whole-cell, or
      perforated, patch-clamp technique. Release was evoked by minimal stimulation
      using brief trains (10 impulses, 50 Hz), and various tests ascertained that this
      stimulation activated single release sites releasing single vesicles. Both AMPA
      and NMDA quantal responses at a given release site varied considerably in
      magnitude, the coefficient of variation (CV) among the synapses averaging 0.39
      and 0.30, respectively. This variability differed among the synapses, from 0.2 to
      0.7, and 0.10 to 0.50, respectively, and CV values of AMPA responses co-varied
      with those of the NMDA responses. Both for AMPA and NMDA, low CV values were
      associated with a Gaussian distribution of EPSC peak values, whereas synapses
      with high CV values displayed distributions skewed towards lower values. Analysis
      of successive NMDA responses during a train revealed a considerable degree of non
      saturation of NMDA receptors by a single vesicle. The results are compatible with
      a quantal variability based, to a large extent, on non-saturated AMPA and NMDA
      responses fluctuating as a function of the amount of transmitter released from
      each vesicle.

PMID- 11230521
TI  - Enhancement of ATP release in hindlimb sympathetic perivascular nerve of the
      golden hamster during hibernation.
AB  - The present study investigated the effects of hibernation and hibernating body
      temperature (10 degrees C) on the relative changes that may occur in adrenergic
      and purinergic perivascular neurotransmission of the golden hamster. The hindlimb
      resistance vessels and the tibial artery of age-matched controls, cold exposed
      controls and hibernated hamsters were examined by pharmacological and
      electrophysiological techniques. At 34 degrees C, electrical field stimulation
      (EFS; supramaximal voltage, 0.5 ms; for 10 s) in all three groups evoked only
      twitch responses at 1-5 Hz, which were inhibited by piridoxal phosphate-6
      azophenyl-2',4'-disulphonic acid (PPADS), a 2PX receptor antagonist. At 10-50 Hz
      the twitch responses were followed by sustained contractile responses, which were
      inhibited by prazosin, an alpha1-adrenoceptor antagonist. These responses were
      markedly enhanced at higher frequencies in hibernated tissues. At 10 degrees C,
      EFS evoked only the PPADS-sensitive transient responses in all the three groups,
      and this was markedly enhanced in hibernated tissues. At 34 degrees C, a single
      stimulus evoked a PPADS-sensitive excitatory junction potential (EJP) in all
      three groups but a train of pulses (e.g. approximately 0.5) evoked EJPs and
      prazosin-sensitive sustained depolarizations. These responses were markedly
      enhanced in hibernated cells. At 10 degrees C, either a single stimulus or a
      train of stimuli evoked only transient PPADS-sensitive EJPs, which were markedly
      enhanced in hibernated cells. The contractile responses and electrical membrane
      responses to exogenous ATP (1-1000 microM) and noradrenaline (0.1-100 microM)
      were unchanged in the three groups at 34 and at 10 degrees C. These results
      suggest that during hibernation enhancement of ATP release from the sympathetic
      perivascular nerves may occur, leading to an efficient means for maintenance of
      vascular tone and peripheral resistance.

PMID- 11230522
TI  - Long term facilitation of respiratory motor output decreases with age in male
      rats.
AB  - Long term facilitation (LTF) is a serotonin-dependent augmentation of respiratory
      motor output (phrenic and hypoglossal) following episodic hypoxia. Since ageing
      influences respiratory control mechanisms and serotonergic function, we tested
      the hypothesis that LTF decreases with age in male rats. Young (3-4 month) and
      aged (13 month) male Sprague-Dawley rats were anaesthetized with urethane,
      vagotomized, paralysed and pump ventilated. Integrated phrenic and hypoglossal
      (XII) nerve activities were measured before (baseline), during and for 60 min
      after three 5 min episodes of isocapnic hypoxia (Pa,O2 35-45 mmHg) separated by 5
      min of hyperoxia (Pa,O2 > 150 mmHg). In young rats, LTF was observed as an
      augmentation in peak integrated phrenic (n = 8) and XII (n = 7) amplitudes
      following episodic hypoxia (56 +/- 14 and 73 +/- 16 % (means +/- S.E.M.) at 60
      min post-hypoxia, respectively; both P < 0.05). In aged rats, LTF was
      significantly increased compared to baseline in phrenic (25 +/- 8 % at 60 min, P
      < 0.05), but not in XII (4 +/- 7 %, P > 0.05) motor output. LTF was significantly
      greater in young than in aged rats in both motor outputs (P < 0.05). Decreased
      phrenic and XII LTF suggests that serotonergic modulation of respiratory motor
      output decreases in ageing male rats. We speculate that decreased serotonergic
      modulation may contribute to age-related breathing disorders.

PMID- 11230524
TI  - Early effects of renal denervation in the anaesthetised rat: natriuresis and
      increased cortical blood flow.
AB  - A novel method of renal denervation was developed based on electro-coagulation of
      tissue containing most of the sympathetic fibres travelling towards the kidney.
      Kidney tissue noradrenaline was decreased to 4.7 % of the content measured in the
      contralateral innervated kidney when studied 3 days postdenervation. The method
      was utilised in anaesthetised rats to examine the effects of denervation within
      the heretofore unexplored first 75 min period postdenervation. Sodium excretion
      (UNaV) increased significantly (+82 %, P < 0.03) over the 25-50 min after
      denervation. In a parallel group, with a lower baseline UNaV, there was also a
      significant increase in UNaV (+54 %, P < 0.03) within the first 25 min. The renal
      perfusion pressure was maintained at a constant value and the glomerular
      filtration rate did not change after denervation. Renal cortical and medullary
      blood flows (CBF, MBF) were estimated as laser Doppler flux and medullary tissue
      ion concentration was estimated as electrical admittance (Y). Following
      denervation, in both groups CBF increased significantly within the first 25 min
      (+12 %, P < 0.01 and +8 %, P < 0.05, respectively) while MBF did not change or
      decreased slightly; Y did not change. The data document the development of
      natriuresis within the first 25-50 min after denervation. The increase in CBF
      indicated that, prior to denervation, the cortical, but not medullary,
      circulation was under a tonic vasoconstrictor influence of the renal nerves. Such
      a dissociation of neural effects on the renal cortical vs. medullary vasculature
      has not been previously described.

PMID- 11230523
TI  - Ischaemia triggered by spreading neuronal activation is inhibited by vasodilators
      in rats.
AB  - It has been previously shown that spreading neuronal activation can generate a
      cortical spreading ischaemia (CSI) in rats. The purpose of the present study was
      to investigate whether vasodilators cause CSI to revert to a normal cortical
      spreading depression (CSD).A KCl-induced CSD travelled from an open cranial
      window to a closed window where the cortex was superfused with physiological
      artificial cerebrospinal fluid (ACSF). At the closed window, recordings revealed
      a short-lasting negative slow potential shift accompanied by a variable, small
      and short initial hypoperfusion followed by hyperaemia and then oligaemia. In
      contrast, spreading neuronal activation locally induced CSI at the closed window
      when ACSF contained a NO. synthase (NOS) inhibitor, N(G)-nitro-L-arginine, and an
      increased K+ concentration ([K+]ACSF). CSI was characterised by a sharp and
      prolonged initial cerebral blood flow decrease to 29 +/- 11 % of the baseline and
      a prolonged negative potential shift. Co-application of a NOa donor, S-nitroso-N
      acetylpenicillamine, and NOS inhibitor with high [K+]ACSF re-established a short
      lasting negative potential shift and spreading hyperaemia typical of CSD.
      Similarly, the NO.-independent vasodilator papaverine caused CSI to revert to a
      pattern characteristic of CSD. In acute rat brain slices, NOS inhibition and high
      [K+]ACSF did not prolong the negative slow potential shift compared to that
      induced by high [K+]ACSF alone. The data indicate that the delayed recovery of
      the slow potential was caused by vasoconstriction during application of high
      [K+]ACSF and a NOS inhibitor in vivo. This supports the possibility of a vicious
      circle: spreading neuronal activation induces vasoconstriction, and
      vasoconstriction prevents repolarisation during CSI. Speculatively, this
      pathogenetic process could be involved in migraine-induced stroke.

PMID- 11230525
TI  - Non-linear changes of electrocortical activity after antenatal betamethasone
      treatment in fetal sheep.
AB  - We determined the effects of betamethasone on the fetal sheep electrocorticogram
      (ECoG) using linear (power spectral) and non-linear analysis. For non-linear
      analysis we used an algorithm based on the Wolf algorithm for the estimation of
      the leading Lyapunov exponent which calculates a prediction error based on the
      course of the time series in the phase space. A high prediction error stands for
      low predictibility or low regularity and vice versa. After 48 h of baseline
      recordings, vehicle (n = 6) or betamethasone (n = 7) at 10 microg h(-1) was
      infused over 48 h to the sheep fetus at 128 days gestational age (0.87 of
      gestation). ECoG spectral analysis revealed no difference in power spectrum
      between vehicle- and betamethasone-treated fetuses. The prediction error of the
      ECoG during REM sleep was higher than during non-REM or quiet sleep in both
      groups (P < 0.0001) revealing lower causality of brain activity during REM sleep.
      During REM sleep, prediction error significantly decreased 18-24 h after onset of
      betamethasone treatment (P < 0.05) and returned to baseline values within the
      following 24 h of continued betamethasone treatment. No ECoG changes were found
      during quiet sleep. Non-linear ECoG changes during metabolically active REM sleep
      accompanied the previously described decrease in cerebral blood flow. These
      results suggest that betamethasone in doses used in perinatal medicine acutely
      alters complex neuronal activity.

PMID- 11230526
TI  - Transcranial magnetic stimulation and stretch reflexes in the tibialis anterior
      muscle during human walking.
AB  - Stretch of the ankle dorsiflexors was applied at different times of the walking
      cycle in 17 human subjects. When the stretch was applied in the swing phase, only
      small and variable reflex responses were observed in the active tibialis anterior
      (TA) muscle. Two of the reflex responses that could be distinguished had
      latencies which were comparable with the early (M1) and late (M3)components of
      the three reflex responses (M1, M2 and M3) observed during tonic dorsiflexion in
      sitting subjects. In the stance phase a single very large response was
      consistently observed in the inactive TA muscle. The peak of this response had
      the same latency as the peak of M3, but in the majority of subjects the onset
      latency was shorter than that of M3. The TA reflex response in the stance phase
      was abolished by ischaemia of the lower leg at the same time as the soleus H
      reflex, suggesting that large muscle afferents were involved in the generation of
      the response. Motor-evoked potentials (MEPs) elicited in the TA by transcranial
      magnetic stimulation (TMS) were strongly facilitated corresponding to the peak of
      the stretch response in the stance phase and the late reflex response in the
      swing phase. A similar facilitation was not observed corresponding to the earlier
      responses in the swing phase and the initial part of the response in stance.
      Prior stretch did not facilitate MEPs evoked by transcranial electrical
      stimulation in the swing phase of walking. However, in the stance phase MEPs
      elicited by strong electrical stimulation were facilitated by prior stretch to
      the same extent as the MEPs evoked by TMS. The large responses to stretch seen in
      the stance phase are consistent with the idea that stretch reflexes are mainly
      involved in securing the stability of the supporting leg during walking. It is
      suggested that a transcortical reflex pathway may be partly involved in the
      generation of the TA stretch responses during walking.

PMID- 11230527
TI  - Excitability of the human trigeminal motoneuronal pool and interactions with
      other brainstem reflex pathways.
AB  - We studied the properties of motoneurones and Ia-motoneuronal connections in the
      human trigeminal system, and their functional interactions with other brainstem
      reflex pathways mediated by non-muscular (Abeta) afferents. With surface EMG
      recordings we tested the recovery cycles of the heteronymous H-reflex in the
      temporalis muscle and the homonymous silent period in the masseter muscle both
      elicited by stimulation of the masseteric nerve at the infratemporal fossa in
      nine healthy subjects. In four subjects single motor-unit responses were recorded
      from the temporalis muscle. In six subjects we also tested the effect of the
      stimulus to the mental nerve on the temporalis H-reflex and, conversely, the
      effect of Ia input (stimulus to the masseteric nerve) on the R1 component of the
      blink reflex in the orbicularis oculi muscle. The recovery cycle of the H-reflex
      showed a suppression peaking at the 5-20 ms interval; conversely the time course
      of the masseteric silent period was facilitated at comparable intervals. The
      inhibition of the test H-reflex was inversely related to the level of background
      voluntary contraction. Single motor units were unable to fire consistently in
      response to the test stimulus at intervals shorter than 50 ms. Mental nerve
      stimulation strongly depressed the H-reflex. The time course of this inhibition
      coincided with the EMG inhibition elicited by mental nerve stimulation during
      voluntary contraction. The trigeminal Ia input facilitated the R1 component of
      the blink reflex when the supraorbital test stimulation preceded the masseteric
      conditioning stimulation by 2 ms. We conclude that the time course of the
      recovery cycle of the heteronymous H-reflex in the temporalis muscle reflects the
      after-hyperpolarization potential (AHP) of trigeminal motoneurones, and that the
      Ia trigeminal input is integrated with other brainstem reflexes.

PMID- 11230529
TI  - Contrasting patterns of X-linked and autosomal nucleotide variation in Drosophila
      melanogaster and Drosophila simulans.
AB  - Surveys of molecular variation in Drosophila melanogaster and Drosophila simulans
      have suggested that diversity outside of Africa is a subset of that within
      Africa. It has been argued that reduced levels of diversity in non-African
      populations reflect a population bottleneck, adaptation to temperate climates, or
      both. Here, I summarize the available single-nucleotide polymorphism data for
      both species. A simple "out of Africa" bottleneck scenario is consistent with
      geographic patterns for loci on the X chromosome but not with loci on the
      autosomes. Interestingly, there is a trend toward lower nucleotide diversity on
      the X chromosome relative to autosomes in non-African populations of D.
      melanogaster, but the opposite trend is seen in African populations. In African
      populations, autosomal inversion polymorphisms in D. melanogaster may contribute
      to reduced autosome diversity relative to the X chromosome. To elucidate the role
      that selection might play in shaping patterns of variability, I present a summary
      of within- and between-species patterns of synonymous and replacement variation
      in both species. Overall, D. melanogaster autosomes harbor an excess of amino
      acid replacement polymorphisms relative to D. simulans. Interestingly, range
      expansion from Africa appears to have had little effect on synonymous-to
      replacement polymorphism ratios.

PMID- 11230528
TI  - Age-related decreases in basal limb blood flow in humans: time course,
      determinants and habitual exercise effects.
AB  - Basal whole-limb blood flow is lower in older than in young healthy sedentary men
      due to a lower limb vascular conductance. In Study 1, we determined whether age
      associated reductions in basal whole-leg (femoral artery) blood flow and vascular
      conductance are modulated by habitual physical activity by studying 89 healthy
      men aged 20-35 or 55-75 years (26 sedentary, 31 physically active and 32
      endurance exercise trained). Femoral blood flow (duplex Doppler) and vascular
      conductance were approximately 20-30 % lower (P < 0.01) in the older men in all
      three physical activity groups. In Study 2, to determine the temporal pattern and
      relation to local metabolism and lean tissue mass of the age-associated
      reductions in femoral blood flow, we studied 142 healthy men aged 18-79 years.
      Femoral blood flow (r = -0.40) and vascular conductance (r = -0.51) were linearly
      and inversely related to age (both P < 0.001). Leg fat-free mass (r = -0.48) and
      estimated leg oxygen consumption (r = -0.49) declined with advancing age (both P
      < 0.001), and were strongly and positively related (r = 0.75; P < 0.001). The age
      associated decline in femoral blood flow correlated with the corresponding
      reductions in leg fat-free mass and estimated leg oxygen consumption (both r =
      0.47; P < 0.001). We concluded that: (1) basal whole-limb blood flow and vascular
      conductance decrease progressively with advancing age in healthy men; (2)
      reductions in both limb fat-free mass and oxygen consumption are related to the
      decline in whole-limb blood flow with age; and (3) habitual aerobic exercise does
      not appear to modulate the age-related reductions in basal limb blood flow and
      vascular conductance.

PMID- 11230530
TI  - Recombination and the frequency spectrum in Drosophila melanogaster and
      Drosophila simulans.
AB  - Most "tests of neutrality" assess whether particular data sets depart from the
      predictions of a standard neutral model with no recombination. For Drosophila,
      where nuclear polymorphism data routinely show evidence of genetic exchange, the
      assumption of no recombination is often unrealistic. In addition, while
      conservative, this assumption is made at the cost of a great loss in power.
      Perhaps as a result, tests of the frequency spectrum based on zero recombination
      suggest an adequate fit of Drosophila polymorphism data to the predictions of the
      standard neutral model. Here, we analyze the frequency spectrum of a large number
      of loci in Drosophila melanogaster and D. simulans using two summary statistics.
      We use an estimate of the population recombination rate based on a laboratory
      estimate of the rate of crossing over per physical length and an estimate of the
      species' effective population size. In contrast to previous studies, we find that
      roughly half of the loci depart from the predictions of the standard neutral
      model. The extent of the departure depends on the exact recombination rate, but
      the global pattern that emerges is robust. Interestingly, these departures from
      neutral expectations are not unidirectional. The large variance in outcomes may
      be due to a complex demographic history and inconsistent sampling, or to the
      pervasive action of natural selection.

PMID- 11230531
TI  - On the origin of Darwin's finches.
AB  - Darwin's finches comprise a group of 15 species endemic to the Galapagos (14
      species) and Cocos (1 species) Islands in the Pacific Ocean. The group is
      monophyletic and originated from an ancestral species that reached the Galapagos
      Archipelago from Central or South America. Descendants of this ancestor on the
      Archipelago then colonized Cocos Island. In the present study, we used sequences
      of two mitochondrial (mt) DNA segments (922 bp of the cytochrome b gene and 1,082
      bp of the control region), as well as two nuclear markers (830 bp of numt2,
      consisting of 140 bp of mtDNA control region and 690 bp of flanking nuclear DNA;
      and 740 bp of numt3, consisting of 420 bp of mt cytochrome b sequence flanked by
      320 bp of nuclear DNA) to identify the species group most closely related to the
      Darwin's finches. To this end, we analyzed the sequences of 28 species
      representing the main groups (tribes) of the family Fringillidae, as well as 2
      outgroup species and 13 species of Darwin's finches. In addition, we used mtDNA
      cytochrome b sequences of some 180 additional Fringillidae species from the
      database for phylogeny reconstruction by maximum-parsimony, maximum-likelihood,
      minimum-evolution, and neighbor-joining methods. The study identifies the
      grassquit genus Tiaris, and specifically the species Tiaris obscura, as the
      nearest living relative of Darwin's finches among the species surveyed. Darwin's
      finches diverged from the Tiaris group shortly after the various extant species
      of Tiaris diverged from one another. The initial adaptive radiation of the Tiaris
      group apparently occurred on the Caribbean islands and then spread to Central and
      South America, from where the ancestors of Darwin's finches departed for the
      Galapagos Islands approximately 2.3 MYA, at the time of the dramatic climatic
      changes associated with the closure of the Panamanian isthmus and the onset of
      Pleistocene glaciation.

PMID- 11230532
TI  - Coevolution of the domains of cytoplasmic tyrosine kinases.
AB  - Many signaling molecules are multidomain proteins that have other domains in
      addition to the catalytic kinase domain. Protein tyrosine kinases almost without
      exception contain Src homology 2 (SH2) and/or SH3 domains that can interact with
      other signaling proteins. Here, we studied evolution of the tyrosine kinases
      containing SH2 and/or SH3 and kinase domains. The three domains seem to have
      duplicated together, since the phylogenetic analysis using parsimony gave almost
      identical evolutionary trees for the separate domains and the multidomain
      complexes. The congruence analysis of the sequences for the separate domains also
      suggested that the domains have coevolved. There are several reasons for the
      domains to appear in a cluster. Kinases are regulated in many ways, and the
      presence of SH2 and SH3 domains at proper positions is crucial. Because all three
      domains can recognize different parts of ligands and substrates, their evolution
      has been interconnected. The reasons for the clustering and coevolution of the
      three domains in protein tyrosine kinases (PTKs) are discussed.

PMID- 11230534
TI  - Tracing the origin of the compensasome: evolutionary history of DEAH helicase and
      MYST acetyltransferase gene families.
AB  - Dosage compensation in Drosophila is mediated by a complex of proteins and RNAs
      called the "compensasome." Two of the genes that encode proteins of the complex,
      maleless (mle) and males-absent-on-the-first (mof), respectively, belong to the
      DEAH helicase and MYST acetyltransferase gene families. We performed
      comprehensive phylogenetic and structural analyses to determine the evolutionary
      histories of these two gene families and thus to better understand the origin of
      the compensasome. All of the members of the DEAH and MYST families of the
      completely sequenced Saccharomyces cerevisiae and Caenorhabditis elegans genomes,
      as well as those so far (June 2000) found in Drosophila melanogaster (for which
      the euchromatic part of the genome has also been fully sequenced) and Homo
      sapiens, were analyzed. We describe a total of 39 DEAH helicases in these four
      species. Almost all of them can be grouped in just three main branches. The first
      branch includes the yeast PRP2, PRP16, PRP22, and PRP43 splicing factors and
      their orthologs in animal species. Each PRP gene has a single ortholog in
      metazoans. The second branch includes just four genes, found in yeast (Ecm16) and
      Drosophila (kurz) and their orthologs in humans and Caenorhabditis. The third
      branch includes (1) a single yeast gene (YLR419w); (2) six Drosophila genes,
      including maleless and spindle-E/homeless; (3) four human genes, among them the
      ortholog of maleless, which encodes RNA helicase A; and (4) three C. elegans
      genes, including orthologs of maleless and spindle-E. Thus, this branch has
      largely expanded in metazoans. We also show that, for the whole DEAH family, only
      MLE and its metazoan orthologs have acquired new protein domains since the
      fungi/animals split. We found a total of 17 MYST family proteins in the four
      analyzed species. We determined putative orthologs of mof in both C. elegans and
      H. sapiens, and we show that the most likely ortholog in yeast is the Sas2 gene.
      Moreover, a paralog of mof exists in Drosophila. All of these results, together
      with those found for a third member of the compensasome, msl-3, suggest that this
      complex emerged after the fungi/animals split and that it may be present in
      mammalian species. Both gene duplication and the acquisition of new protein
      modules may have played important roles in the origin of the compensasome.

PMID- 11230533
TI  - The Drosophila alcohol dehydrogenase gene may have evolved independently of the
      functionally homologous medfly, olive fly, and flesh fly genes.
AB  - cDNAs for alcohol dehydrogenase (ADH) isozymes were cloned and sequenced from two
      tephritid fruit flies, the medfly Ceratitis capitata and the olive fly Bactrocera
      oleae. Because of the high sequence divergence compared with the Drosophila
      sequences, the medfly cDNAs were cloned using sequence information from the
      purified proteins, and the olive fly cDNAs were cloned by functional
      complementation in yeast. The medfly peptide sequences are about 83% identical to
      each other, and the corresponding mRNAs have the tissue distribution shown by the
      corresponding isozymes, ADH-1 and ADH-2. The olive fly peptide sequence is more
      closely related to medfly ADH-2. The tephritid ADHs share less than 40% sequence
      identity with Drosophila ADH and ADH-related genes but are >57% identical to the
      ADH of the flesh fly Sarcophaga peregrina, a more distantly related species. To
      explain this unexpected finding, it is proposed that the ADH: genes of the family
      Drosophilidae may not be orthologous to the ADH: genes of the other two families,
      Tephritidae and Sarcophagidae.

PMID- 11230535
TI  - An error-correcting map for quartets can improve the signals for phylogenetic
      trees.
AB  - From the DNA sequences for N taxa, the (generally unknown) phylogenetic tree T
      that gave rise to them is to be reconstructed. Various methods give rise, for
      each quartet J consisting of exactly four taxa, to a predicted tree L(J) based
      only on the sequences in J, and these are then used to reconstruct T. The author
      defines an "error-correcting map" (Ec), which replaces each L(J) with a new tree,
      Ec(L)(J), which has been corrected using other trees, L(K), in the list L. The
      "quartet distance" between two trees is defined as the number of quartets J on
      which the two trees differ, and two distinct trees are shown to always have
      quartet distance of at least N - 3. If L has quartet distance at most (N - 4)/2
      from T, then Ec(L) will coincide with the correct list for T; and this result
      cannot be improved. In general, Ec can correct many more errors in L. Iteration
      of the map Ec may produce still more accurate lists. Simulations are reported
      which often show improvement even when the quartet distance considerably exceeds
      (N - 4)/2. Moreover, the Buneman tree for Ec(L) is shown to refine the Buneman
      tree for L, so that strongly supported edges for L remain strongly supported for
      Ec(L). Simulations show that if methods such as the C-tree or hypercleaning are
      applied to Ec(L), the resulting trees often have more resolution than when the
      methods are applied only to L.

PMID- 11230536
TI  - Performance of a divergence time estimation method under a probabilistic model of
      rate evolution.
AB  - Rates of molecular evolution vary over time and, hence, among lineages. In
      contrast, widely used methods for estimating divergence times from molecular
      sequence data assume constancy of rates. Therefore, methods for estimation of
      divergence times that incorporate rate variation are attractive. Improvements on
      a previously proposed Bayesian technique for divergence time estimation are
      described. New parameterization more effectively captures the phylogenetic
      structure of rate evolution on a tree. Fossil information and other evidence can
      now be included in Bayesian analyses in the form of constraints on divergence
      times. Simulation results demonstrate that the accuracy of divergence time
      estimation is substantially enhanced when constraints are included.

PMID- 11230537
TI  - Phylogenetic analyses of two "archaeal" genes in thermotoga maritima reveal
      multiple transfers between archaea and bacteria.
AB  - The genome sequence of Thermotoga maritima revealed that 24% of its open reading
      frames (ORFs) showed the highest similarity scores to archaeal genes in BLAST
      analyses. Here we screened 16 strains from the genus Thermotoga and other related
      Thermotogales for the occurrence of two of these "archaeal" genes: the gene
      encoding the large subunit of glutamate synthase (gltB) and the myo-inositol 1P
      synthase gene (ino1). Both genes were restricted to the Thermotoga species within
      the Thermotogales. The distribution of the two genes, along with results from
      phylogenetic analyses, showed that they were acquired from Archaea during the
      divergence of the Thermotogales. Database searches revealed that three other
      bacteria-Dehalococcoides ethenogenes, Sinorhizobium meliloti, and Clostridium
      difficile-possess archaeal-type gltBs, and the phylogenetic analyses confirmed at
      least two lateral gene transfer (LGT) events between Bacteria and Archaea. These
      LGT events were also strongly supported by gene structure data, as the three
      domains in bacterial-type gltB are homologous to three independent ORFs in
      Archaea and Bacteria with archaeal-type gltBs. The ino1 gene has a scattered
      distribution among Bacteria, and apart from the Thermotoga strains it is found
      only in Aquifex aeolicus, D. ethenogenes, and some high-G+C Gram-positive
      bacteria. Phylogenetic analysis of the ino1 sequences revealed three highly
      supported prokaryotic clades, all containing a mixture of archaeal and bacterial
      sequences, and suggested that all bacterial ino1 genes had been recruited from
      archaeal donors. The Thermotoga strains and A. aeolicus acquired this gene
      independently from different archaeal species. Although transfer of genes from
      hyperthermophilic Archaea may have facilitated the evolution of bacterial
      hyperthermophily, between-domain transfers also affect mesophilic species. For
      hyperthermophiles, we hypothesize that LGT may be as much a consequence as the
      cause of adaptation to hyperthermophily.

PMID- 11230538
TI  - Polymorphism in abalone fertilization proteins is consistent with the neutral
      evolution of the egg's receptor for lysin (VERL) and positive darwinian selection
      of sperm lysin.
AB  - The evolution of species-specific fertilization in free-spawning marine
      invertebrates is important for reproductive isolation and may contribute to
      speciation. The biochemistry and evolution of proteins mediating species-specific
      fertilization have been extensively studied in the abalone (genus Haliotis). The
      nonenzymatic sperm protein lysin creates a hole in the egg vitelline envelope by
      species-specifically binding to its egg receptor, VERL. The divergence of lysin
      is promoted by positive Darwinian selection. In contrast, the evolution of VERL
      does not depart from neutrality. Here, we cloned a novel nonrepetitive region of
      VERL and performed an intraspecific polymorphism survey for red (Haliotis
      rufescens) and pink (Haliotis corrugata) abalones to explore the evolutionary
      forces affecting VERL. Six statistical tests showed that the evolution of VERL
      did not depart from neutrality. Interestingly, there was a subdivision in the
      VERL sequences in the pink abalone and a lack of heterozygous individuals between
      groups, suggesting that the evolution of assortative mating may be in progress.
      These results are consistent with a model which posits that egg VERL is neutrally
      evolving, perhaps due to its repetitive structure, while sperm lysin is subjected
      to positive Darwinian selection to maintain efficient interaction of the two
      proteins during sperm competition.

PMID- 11230539
TI  - Mobile elements and the genesis of microsatellites in dipterans.
AB  - Factors that influence the genesis and genomic distribution of microsatellite DNA
      are poorly understood. We have identified a novel class of Dipteran mobile
      elements, mini-me elements, which help elucidate both of these issues. These
      retroposons contain two internal proto-microsatellite regions that commonly
      expand into lengthy microsatellite repeats. These elements are highly abundant,
      accounting for approximately 1.2% of the Drosophila melanogaster genome, giving
      them the potential to be a prolific source of microsatellite DNA variation. They
      also give us the opportunity to observe the outcomes of multiple microsatellite
      genesis events (initiating from the same proto-microsatellite) at separate mini
      me loci. Based on these observations, we determined that the genesis of
      microsatellites within mini-me elements occurs through two separate mutational
      processes: the expansion of preexisting tandem repeats and the conversion of
      sequence with high cryptic simplicity into tandemly repetitive DNA. These modes
      of microsatellite genesis can be generalized beyond the case of mini-me elements
      and help to explain the genesis of microsatellites in any sequence region that is
      not constrained by selection.

PMID- 11230540
TI  - Molecular remodeling of members of the relaxin family during primate evolution.
AB  - Employing comparative analysis of the cDNA-coding sequences of the unique
      preprorelaxin of the Afro-lorisiform Galago crassicaudatus and the Malagasy lemur
      Varecia variegata and the relaxin-like factor (RLF) of G. crassicaudatus, we
      demonstrated distinct differences in the dynamics of molecular remodeling of both
      hormones during primate evolution. The lorisiform and lemuriform preprorelaxin
      sequences encoded identical hormones, providing the first endocrinological
      evidence for the monophyletic origin of all Strepsirrhini. Structural analysis
      revealed the lemuriform members of the relaxin family to be potentially bioactive
      single-gene products. In contrast to the "two-prong" relaxin receptor-binding
      motif (RELVR) present within the B-domains of other primate relaxins,
      strepsirrhine relaxin contained a unique "three-prong" motif (RRLIR) with highest
      sequence homology to the receptor-binding motif of the evolutionarily much older
      skate relaxin. In contrast to relaxin, the RLF molecule was highly conserved
      during primate evolution and contained within its B-domain the putative relaxin
      receptor-binding motif and a pentameric sequence implicated in binding to
      specific RLF receptors. Mutually exclusive expression of strepsirrhine
      preprorelaxin and RLF were observed in the fetal villous trophoblast cells of the
      strepsirrhine placenta and postpubertal testicular Leydig cells, respectively,
      reflecting distinct functional roles for both hormones within the reproductive
      tract of Strepsirrhini.

PMID- 11230541
TI  - Codon bias and base composition are poor indicators of horizontally transferred
      genes.
AB  - Horizontal gene transfer is now recognized as an important mechanism of
      evolution. Several methods to detect horizontally transferred genes have been
      suggested. These methods are based on either nucleotide composition or the
      failure to find a similar gene in closely related species. Genes that evolve
      vertically between closely related species can be divided into those that retain
      homologous chromosomal positions (positional orthologs) and those that do not. By
      comparing open reading frames in the Escherichia coli and Salmonella typhi
      genomes, we identified 2,728 positional orthologs since these species split 100
      MYA. A group of 1,144 novel E. coli genes were unusually diverged from their S.
      typhi counterparts. These novel genes included those that had been horizontally
      transferred into E. coli, as well as members of gene pairs that had been
      rearranged or deleted. Positional orthologs were used to investigate
      compositional methods of identifying horizontally transferred genes. A large
      number of E. coli genes with normal nucleotide composition have no apparent
      ortholog in S. typhi, and many genes of atypical composition do, in fact, have
      positional orthologs. A phylogenetic approach was employed to confirm selected
      examples of horizontal transmission among the novel groups of genes. Our analysis
      of 80 E. coli genes determined that a number of genes previously classified as
      horizontally transferred based on base composition and codon bias were native,
      and genes previously classified as native appeared to be horizontally
      transferred. Hence, atypical nucleotide composition alone is not a reliable
      indicator of horizontal transmission.

PMID- 11230542
TI  - A maximum-likelihood approach to fitting equilibrium models of microsatellite
      evolution.
AB  - Here, we develop a new approach to Markov chain modeling of microsatellite
      evolution through polymerase slippage and introduce new models: a "constant
      slippage-rate" model, in which there is no dependence of slippage rate on
      microsatellite length, as envisaged by Moran; and a "linear-with-constant" model,
      in which slippage rate increases linearly with microsatellite length, but the
      line of best fit is not constrained to go through the origin. We show how these
      and a linear no-constant model can be fitted to data hierarchically using maximum
      likelihood. This has advantages over previous methods in allowing statistical
      comparisons between models. When applied to a previously analyzed data set, the
      method allowed us to statistically establish that slippage rate increases with
      microsatellite length for dinucleotide microsatellites in humans, mice, and fruit
      flies, and suggested that no slippage occurs in very short microsatellites of one
      to four repeats. The suggestion that slippage rates are zero or close to zero for
      very short microsatellites of one to four repeats has important implications for
      understanding the mechanism of polymerase slippage.

PMID- 11230543
TI  - Nuclear-encoded, plastid-targeted genes suggest a single common origin for
      apicomplexan and dinoflagellate plastids.
AB  - The phylum Apicomplexa encompasses a large number of intracellular protozoan
      parasites, including the causative agents of malaria (Plasmodium), toxoplasmosis
      (Toxoplasma), and many other human and animal diseases. Apicomplexa have recently
      been found to contain a relic, nonphotosynthetic plastid that has attracted
      considerable interest as a possible target for therapeutics. This plastid is
      known to have been acquired by secondary endosymbiosis, but when this occurred
      and from which type of alga it was acquired remain uncertain. Based on the
      molecular phylogeny of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) genes, we
      provide evidence that the apicomplexan plastid is homologous to plastids found in
      dinoflagellates-close relatives of apicomplexa that contain secondary plastids of
      red algal origin. Surprisingly, apicomplexan and dinoflagellate plastid-targeted
      GAPDH sequences were also found to be closely related to the plastid-targeted
      GAPDH genes of heterokonts and cryptomonads, two other groups that contain
      secondary plastids of red algal origin. These results address several outstanding
      issues: (1) apicomplexan and dinoflagellate plastids appear to be the result of a
      single endosymbiotic event which occurred relatively early in eukaryotic
      evolution, also giving rise to the plastids of heterokonts and perhaps
      cryptomonads; (2) apicomplexan plastids are derived from a red algal ancestor;
      and (3) the ancestral state of apicomplexan parasites was photosynthetic.

PMID- 11230544
TI  - Evolution and discontinuous distribution of Rex3 retrotransposons in fish.

PMID- 11230545
TI  - Slow rates of evolution and sequence homogenization in an ancient satellite DNA
      family of sturgeons.

PMID- 11230546
TI  - Elongation factor 1-alpha sequences alone do not assist in resolving the position
      of the acoela within the metazoa.

PMID- 11230548
TI  - PPP family of protein Ser/Thr phosphatases: two distinct branches?

PMID- 11230547
TI  - An unusual vertebrate LTR retrotransposon from the cod Gadus morhua.

PMID- 11230549
TI  - Is ethanol genotoxic? A review of the published data.
AB  - A great many studies have been carried out on the toxicology of ethanol, the
      majority in the context of the effects of the consumption of alcohol in
      beverages. Published information relevant to the assessment of the possible
      genotoxic potential of ethanol has been reviewed and evaluated in terms of the
      safety of ethanol as an industrial chemical, rather than as a component of
      beverages. The available data on ethanol from standard genotoxicity test methods
      are incomplete. There is clear evidence that ethanol is not a bacterial or
      mammalian cell mutagen but in vitro assays for chromosome aberration, although
      mostly negative, have generally not included exogenous metabolic activation.
      Evidence from the use of ethanol as a vehicle control suggests that it is not
      mutagenic or clastogenic in vitro. Reported tests for chromosome aberration
      induction in vivo are all negative and only a minority of micronucleus tests are
      positive. Conflicting results have been reported for the dominant lethal assay,
      although an inter-laboratory study performed to OECD guidelines was negative.
      There is some evidence that ethanol induces SCE in vivo and can also act as an
      aneugen at high doses. Many in vivo studies were designed to model alcoholism and
      used very high doses, sometimes for long periods. Outcomes may have been affected
      by disturbances of metabolism giving rise to secondary effects. It is concluded
      that there is no significant evidence that ethanol is a genotoxic hazard
      according to the criteria normally applied for the purpose of classification and
      labelling of industrial chemicals. Some degree of genotoxicity may result from
      excessive alcohol drinking, but this is not considered relevant to any
      conceivable exposure obtainable by either inhalation or dermal exposure in the
      workplace.

PMID- 11230550
TI  - A test of the mutagenicity of cooked meats in vivo.
AB  - There is a correlation between intestinal cancer and diets high in meat, so fried
      beef, chicken, lamb, pork and fish were tested for their ability to induce
      mutations in the small intestine of mice. The mice were bred to be heterozygous
      at the Dlb-1 locus so that loss of the dominant Dlb-1 b allele by mutation could
      be detected. Mice were fed the AIN-76A diet (which contains 50% of the calories
      in the form of sucrose) or an isocaloric diet in which the sucrose was replaced
      by meat or fish, for 5 or 9 weeks. Manifestation of mutants requires
      approximately 1 week in this system, so this corresponds to an effective exposure
      of 4 and 8 weeks, respectively. There was no significant difference in the
      weights of animals on the different diets, and no difference in mutant frequency.
      Several food mutagens were present, but at low levels. These results, when
      considered in the light of tests of 2-amino-1-methyl-6-phenylimidazo[4,5-b]
      pyridine and amino(alpha)carboline at much higher doses (Zhang,X.-B., Tao,K.S.,
      Urlando,C., Shaver-Walker,P. and Heddle,J.A. (1996) MUTAGENESIS:, 11, 43-48),
      indicate that there is no highly mutagenic compound missed by previous testing
      with bacterial assays and that mixtures of heterocyclic amines at low levels do
      not show great synergy.

PMID- 11230551
TI  - Sequence of centromere separation: effect of 5-azacytidine-induced epigenetic
      alteration.
AB  - The factors which control the sequential separation of the various chromosomes in
      a genome at the meta-anaphase junction are not well understood. In genomes in
      which separation is correlated with the quantity of pericentric heterochromatin
      one factor appears to be the epigenetic nature, namely condensation, of
      pericentric heterochromatin. When we induced decondensation of pericentric
      heterochromatin in mouse cells with 10(-6), 4x 10(-6) and 6x10(-6) M 5
      azacytidine (5-AC) for 8 h, it resulted in alteration of the sequence of
      centromere separation. The centromeres which lacked pericentric heterochromatin
      appeared not to have been affected because there could not be an epigenetic
      alteration induced by 5-AC. The major effect was on chromosomes with the largest
      quantity of pericentric heterochromatin. These chromosomes separated at
      significantly higher frequency than in the untreated population. We also treated
      human cells, in which separation does not depend upon the quantity of
      heterochromatin, with 2x10(-5) and 6x10(-6) M 5-AC for 5 and 8 h. Compared with
      the control, 5-AC treatment resulted in an increased frequency of separated
      centromeres of acrocentric chromosomes in relation to those of non-acrocentric
      chromosomes. In the control the acrocentric chromosomes are the last to separate;
      in the treated population there was almost random separation of the two types of
      chromosomes. This epigenetic alteration might be another factor which results in
      genesis of aneuploidy.

PMID- 11230552
TI  - PHA-induced cell proliferation rescues human peripheral blood lymphocytes from X
      ray-induced apoptosis.
AB  - Human peripheral blood G(0) lymphocytes were X-irradiated and allowed to recover
      for different periods both in the presence and absence of phytohemagglutinin
      (PHA). For each experimental condition the induction of apoptosis was
      investigated by nuclear morphology and formation of both DNA laddering and high
      molecular weight DNA fragments by pulsed field gel electrophoresis. The results
      showed that PHA cell growth stimulation could rescue peripheral blood lymphocytes
      (PBLs) from X-ray-induced apoptotic cell death. Instead, most X-irradiated
      lymphocytes held in G(0) phase, once they were committed to apoptosis, inexorably
      executed the process. These data indicate that the proliferative status of PBLs
      can influence apoptotic cell death: PHA-stimulated PBLs appear to be more
      radioresistant as a result of a less efficient apoptotic process. Therefore, in
      current tests for mutagenicity or cytotoxicity and in biodosimetrical studies the
      possible role of apoptosis has to be considered.

PMID- 11230553
TI  - Detection of DNA primary damage by premature chromosome condensation in human
      peripheral blood lymphocytes treated with methyl methanesulfonate.
AB  - Methyl methanesulfonate (MMS) is a direct acting methylating agent which produces
      apurinic sites that are transformed into DNA single-strand breaks by base
      excision repair. MMS-induced DNA lesions have to be transformed by DNA synthesis
      in order to give rise to chromosomal damage. In this study the premature
      chromosome condensation (PCC) technique was used in G(1) human lymphocytes
      treated with MMS to investigate whether, with this technique, chromosomal damage
      could be detected without the cell needing to undergo DNA synthesis. A dose
      dependent increase in chromosomal fragmentation was indeed observed in G(1)
      lymphocytes. MMS treatment at 1.3, 2.5 and 5 mM was characterized by the
      appearance of highly fragmented chromosomes. This observation induced us to
      further investigate whether this effect was more connected with triggering of
      apoptotic cell death than a consequence of the PCC technique. Data obtained by
      nuclear morphology analysis, by Trypan blue exclusion assay and pulsed field gel
      electrophoresis seem to suggest that the observed chromosome fragmentation could
      be due to the onset of apoptosis. Consequently, one should bear in mind that the
      PCC technique can overestimate chromosomal damage when apoptosis is also induced.

PMID- 11230554
TI  - Effects of styrene-7,8-oxide over p53, p21, bcl-2 and bax expression in human
      lymphocyte cultures.
AB  - Styrene is one of the most important organic chemicals in use today. The highest
      human exposures to styrene take place by inhalation during the production of
      fibreglass-reinforced plastics. Styrene is oxidized by hepatic cytochrome P450 to
      styrene-7,8-oxide (SO), an epoxide that has been shown to induce chromosome
      aberrations, sister chromatid exchanges and micronuclei in many cell systems. In
      this work, the effect of SO on the expression of some genes involved in the cell
      cycle and apoptosis regulation in human white blood cells was studied. Lymphocyte
      cultures from four donors were exposed to 50 and 200 microM SO, 1% DMSO being the
      control. Aliquots of the cultures were taken at six different time points (30,
      36, 42, 48, 60 and 72 h), total mRNA was extracted in each one of them and RT-PCR
      was carried out to analyze the expression of the genes p53, p21, bcl-2 and bax.
      Moreover, a cytokinesis block assay was performed to estimate cell proliferation
      kinetics by calculating the cytokinesis block proliferation index (CBPI), and to
      evaluate the number of cells undergoing apoptosis. Furthermore, apoptotic events
      were detected by the DNA fragmentation assay. In our results, a high
      interindividual variation in the expression of the studied genes was observed.
      Expression curves obtained for the four genes, together with the data from the
      CBPI and apoptotic cells scored, suggest that exposure to high levels of SO may
      induce a delay in the cell cycle, probably directed to allowing repair systems to
      act on the genotoxic damage produced, more than driving cells towards programmed
      cell death.

PMID- 11230555
TI  - Automatic analysis of slides processed in the Comet assay.
AB  - In recent years the Comet assay (or single cell gel electrophoresis assay) has
      been established as a rapid and sensitive method for the detection of DNA damage.
      For early genotoxicity screening of new chemical entities in industrial
      toxicology, the Comet assay is more and more used for assessment of the DNA
      damaging potential of a test compound. In order to increase compound screening
      throughput, we have established an image analysis system for fully automated
      measurement of microscope slides processed in the Comet assay. For the
      comparative investigation various cell types, such as V79 Chinese hamster cells,
      mouse lymphoma cells and human leukocytes, were treated with several test
      compounds. Using tail moment as the quantitative parameter for comet formation,
      we show a very high correlation between our automatic image analysis system and a
      commercially available, interactive system (Comet Assay II of Perceptive
      Instruments). The possibility of analyzing 50 samples within 1 day and the high
      reproducibility of results make automated image processing a powerful tool for
      automatic analysis of slides processed in the Comet assay.

PMID- 11230556
TI  - Preliminary study of cytogenetic damage in personnel exposed to anesthetic gases.
AB  - Occupational exposure to anesthetic gases is associated with various adverse
      health effects. Genetic material has been shown to be a sensitive target of
      numerous harmful agents. The aim of this study was to examine whether chromosomal
      damage could serve to indicate exposure to anesthetics. A group of 43 hospital
      workers of three professions (anesthesiologists, technicians and operating room
      nurses) and 26 control subjects were examined for chromosome aberrations, sister
      chromatid exchanges and micronucleus frequency. The exposed groups matched in
      duration of exposure to anesthetics, but not in age. An equal ratio between women
      and men was possible in all groups except nurses. Likewise, the ratio between
      smokers and non-smokers was also not comparable. An increase in chromosome damage
      was found in all exposed groups. While the increase in sister chromatid exchange
      frequency was not significant, chromosome aberrations and micronucleus frequency
      increased significantly, showing higher rates in women. The results suggest that
      the micronucleus test is the most sensitive indicator of changes caused by
      anesthetic gases. The observed difference between sexes with respect to exposure
      risk call for further, targeted investigations.

PMID- 11230557
TI  - Chromosomal composition of micronuclei in mouse NIH 3T3 cells treated with
      acrylamide, extract of Tripterygium hypoglaucum (level) hutch, mitomycin C and
      colchicine, detected by multicolor FISH with centromeric and telomeric DNA
      probes.
AB  - The chromosomal composition of micronuclei (MN) induced by the model mutagens
      mitomycin (MMC) and colchicine (COL) as well as by acrylamide (AA) and the
      traditional Chinese medicine Tripterygium hypoglaucum (level) hutch (THH) in NIH
      3T3 cells was analyzed by multicolor fluorescence in situ hybridization (FISH)
      using DNA probes for the centromere repeated minor satellite DNA and the
      telomeric hexamer repeat (TTAGGG). The majority of MN (78.6%) from treatment with
      MMC (0.1 microg/ml) did not show centromeric signals, reflecting the clastogenic
      action of MMC. Following treatment with COL (0.1 microg/ml), 74.5% of the MN
      showed centromeric signals and several telomeric signals, indicating that MN
      induced by this well-known aneugen were mainly composed of whole chromosomes.
      After treatment with AA (100, 200 and 400 microg/ml) both MN containing whole
      chromosomes and MN containing acentric fragments were found to increase in a dose
      dependent manner, demonstrating that AA is not only a clastogen but also an
      aneugen. THH induced a high frequency of MN harboring whole chromosomes at all
      concentrations tested (5, 10 and 20 microl/ml) and produced a dose-dependent
      increase in fragment-containing MN, indicating that THH has both aneugenic and
      clastogenic potential.

PMID- 11230558
TI  - The mutagenic potential of acetonitrile in the bone marrow and peripheral blood
      of the mouse.
AB  - Acetonitrile was tested for its ability to induce clastogenic or aneugenic
      effects through the induction of micronucleated polychromatic erythrocytes
      (MNPCE) in mouse bone marrow and peripheral blood. Groups of NMRI mice, five
      males and five females, were administered a single i.p. dose of acetonitrile,
      corresponding to the maximum tolerated dose (MTD), 100 or 125 mg/kg body wt for
      males and females, respectively. Bone marrow was sampled at 18, 24 or 36 h after
      treatment, while peripheral blood was sampled before and 24, 48, 72 and 96 h
      after treatment. Positive controls were administered cyclophosphamide (65 mg/kg
      i.p.). Acetonitrile did not increase the incidence of MNPCE in either bone marrow
      or peripheral blood in male mice or in peripheral blood in females. A small, but
      statistically significant (P: < 0.05), increase was observed in female bone
      marrow 36 h after administration, but since this was within the range of the
      control data it is not considered to be of biological significance.
      Cyclophosphamide increased the incidence of MNPCE in bone marrow and peripheral
      blood of both sexes. It is concluded that acetonitrile is neither clastogenic nor
      aneugenic in the bone marrow of the mouse at the MTD.

PMID- 11230559
TI  - Genotoxins and the initiation of sporadic breast cancer.
AB  - Breast cancer is the most frequently diagnosed female malignancy world-wide. The
      aetiology of the majority of cases remains obscure and the only genotoxin as yet
      known to initiate breast cancer is ionizing radiation. High penetrance
      susceptibility genes probably account for no more than 5-10% of cases. The
      breast, which consists of 70-90% adipose tissue, has a unique morphological
      structure. Dispersed within it are the functional elements that are lined with
      cancer-susceptible epithelial cells. Numerous dietary and/or environmental fat
      soluble compounds are known to be rodent mammary carcinogens. Extracts of lipid
      obtained following collagenase digestion of elective reduction mammoplasty
      tissues from UK resident women showed activity in short-term genotoxicity assays
      in 40% of cases. More active lipid extracts tended to come from donors whose
      human mammary epithelial cells (HMECs) exhibited pre-existing DNA single-strand
      breaks (SSBs). Lipid extracts also induced morphological transformation of
      mammalian cells in vitro. To increase cohort size, extracts of UK breast milk
      were examined for genotoxicity and similar activity profiles were observed.
      Viable cells, a large percentage of which were HMECs, were recovered from breast
      milk and examined for pre-existing SSBs and for the ability of the donor's own
      milk extract to induce SSBs. Again, donors whose untreated cells contained the
      most SSBs tended to yield genotoxic breast milk extracts. Breast milk cells were
      also able to activate rodent mammary carcinogens to DNA-damaging species. These
      studies provide good evidence for in vivo exposure of HMECs to genotoxic agents
      years before the peak in occurrence of sporadic breast cancer. Work is in
      progress to characterize these agents and to determine their possible role in
      breast cancer aetiology.

PMID- 11230560
TI  - Induction and time-dependent accumulation of micronuclei in peripheral blood of
      transgenic p53+/- mice, Tg.AC (v-Ha-ras) and parental wild-type (C57BL/6 and
      FVB/N) mice exposed to benzene by inhalation.
AB  - In this study, we determined the induction and time-dependent accumulation of
      micronuclei in the peripheral blood of transgenic C57BL/6 p53+/- mice (p53+/-
      mice), FVB/N Tg.AC v-Ha-ras mice (Tg.AC mice) and their isogenic parental
      strains, FVB/N and C57BL/6 following inhalation exposure to benzene. Our
      objective was to determine the impact of p53 heterozygosity in p53+/- mice and
      the v-Ha-ras transgene in Tg.AC mice on micronuclei induction following exposure
      to inhaled benzene. A flow cytometric technique that distinguishes micronucleated
      red blood cells (MN-RBC) from micronucleated reticulocytes (MN-RET) was used.
      Mice were exposed to 0, 100 or 200 p.p.m. benzene using three different exposure
      regimens that resulted in an equal weekly cumulative exposure (3000 p.p.m.x
      hours) to benezene: 100 p.p.m. for 6 h/day, 5 days/week, Monday to Friday (M-F);
      100 p.p.m. for 10 h/day, 3 days/week, Monday, Wednesday, Friday (MWF); and 200
      p.p.m. for 5 h/day, 3 days/week MWF. Significant elevations of MN-RBC and MN-RET
      were observed from 1 week exposure in all of the benzene-exposed groups that
      increased in a time-dependent manner for up to 13 weeks exposure. Fewer MN-RBC
      and MN-RET were induced in the 200 p.p.m. benzene exposure group than in mice
      exposed to 100 p.p.m. The reduction in the frequency of MN-RBC in the 200
      p.p.m.x5 h benzene exposure group is probably due to metabolic saturation
      resulting in a lower bone marrow dose (concentration x time) than in the 100
      p.p.m. exposure groups. No differences were observed in the frequency of MN-RBC
      or MN-RET in Tg.AC compared with the FVB/N isogenic controls. At certain time
      points the frequency of micronuclei was less in the heterozygous p53+/- mice than
      determined in the wild-type C57BL/6 isogenic parental strain. These results
      indicate that the heterozygous state in p53+/- mice, but not the v-Ha-ras
      transgene in Tg.AC mice can influence the induction of micronuclei by benzene.

PMID- 11230561
TI  - The preparation of anthraquinone used in the National Toxicology Program cancer
      bioassay was contaminated with the mutagen 9-nitroanthracene.
AB  - Commercial anthraquinone (AQ) (9,10-anthracenedione) is produced by at least
      three different production methods worldwide: oxidation of anthracene (AQ-OX),
      Friedel-Crafts technology (AQ-FC) and by Diels-Alder chemistry (AQ-DA), with the
      final product varying in color and purity. AQ-OX begins with anthracene produced
      from coal tar and different lots can contain various contaminants, particularly
      the mutagenic isomers of nitroanthracene. AQ has been reported to be negative in
      a variety of genotoxicity tests including numerous Ames Salmonella mutagenicity
      assays. In addition, we report that AQ-DA is negative in the Salmonella
      Escherichia coli reverse mutation assays, the L5178Y mouse lymphoma forward
      mutation assay, for inducing chromosomal aberrations, polyploidy or
      endoreduplication in Chinese hamster ovary cells, and in the in vivo mouse
      micronucleus assay. Further, a previous 18 month bioassay conducted with AQ
      administered to male and female B6C3F(1) and (C57BL/6xAKR)F(1) mice reported no
      induction of cancer. Thus, it was somewhat unexpected that in a long-term study
      conducted by the National Toxicology Program (NTP) AQ-OX induced a weak to modest
      increase in tumors in the kidney and bladder of male and female F344/N rats and a
      strong increase in the livers of male and female B6C3F(1) mice. In the studies
      reported here, a sample of the AQ-OX used in the NTP bioassay was shown to be
      mutagenic in the Ames tester strains TA98, TA100 and TA1537. Addition of an S9
      metabolic activation system decreased or eliminated the mutagenic activity. In
      contrast, the purified NTP AQ-OX as well as the technical grade samples AQ-FC and
      AQ-DA were not mutagenic in the Ames test. The chemical structure of AQ does not
      suggest that the parent compound would be DNA reactive. Therefore, a mutagenic
      contaminant was present in the NTP bioassay sample that is either directly
      mutagenic or can be activated by bacterial metabolism. Analytical studies showed
      that the primary contaminant 9-nitroanthracene (9-NA) was present in the NTP AQ
      OX at a concentration of 1200 p.p.m., but not in the purified material. The 9-NA
      and any other contaminants that might have been present in the NTP AQ-OX induced
      measurable mutagenicity at 9-NA concentrations as low as 0.15 microg/plate in
      tester strain TA98, indicating potent mutagenic activity. On the basis of
      revertants per microgram, 9-NA was more potent than benzo[a]pyrene (B[a]P) and
      was about equally as potent as the 2-nitrofluorene run concurrently as positive
      controls. TD(50) quantitative carcinogenicity potency estimates indicate that a
      carcinogen of a potency in the range between B[a]P and dimethylnitrosamine would
      be required to produce the observed carcinogenic response at the levels of the
      contaminants found in the test sample. While recognizing that there are
      limitations in extrapolating mutagenic potency to potential carcinogenic potency,
      these estimates do indicate that it is plausible that the 9-NA contaminant might
      have been responsible for all of the tumor induction observed in the NTP study.
      In fact, in the absence of reliable cancer data, the genetic toxicology profile
      indicates that AQ would not be a genotoxic carcinogen. Thus, no conclusion as to
      the carcinogenic activity of AQ can be made at this time.

PMID- 11230562
TI  - Industrial Genotoxicology Group (IGG): cytotoxicity in vitro, Royal Society of
      Medicine, London, UK, 6 December 1999.

PMID- 11230563
TI  - The Arabidopsis sensor His-kinase, AHk4, can respond to cytokinins.
AB  - His-to-Asp (His-->Asp) phosphorelay mechanisms are presumably involved in
      propagation of certain environmental stimuli, including phytohormones, in
      Arabidopsis thaliana. In addition to the previously characterized His-kinases,
      namely, the ETR1 family of ethylene receptors, CKI1 cytokinin-sensor, and ATHK1
      osomo-sensor, this higher plant has three more His-kinases (named AHK2, AHK3, and
      AHK4). By employing the well-known His-->Asp phosphorelay systems in both the
      fission yeast and Escherichia coli, evidence is presented showing that the AHK4
      His-kinase has an ability to serve as a cytokinin-responsive environmental
      sensor. Taking advantage of this AHK4-dependent His-->Asp phosphorelay system in
      E. coli, a phosphorelay interaction between the Arabidopsis His-kinase and
      histidine-containing phosphotransmitters (AHPs) was also demonstrated for the
      first time.

PMID- 11230564
TI  - Plants steroid hormones, brassinosteroids: current highlights of molecular
      aspects on their synthesis/metabolism, transport, perception and response.
AB  - Brassinosteroids (BRs) are plant steroids essential for normal growth and
      development and can be defined as steroids that carry an oxygen moiety at C-3 and
      additional ones at one or more of the C-2, C-6, C-22 and C-23 carbon atoms. BR
      biosynthesis and metabolism mutants have been obtained and the corresponding
      genes cloned. These include genes encoding 5alpha-reductase and cytochrome P450
      enzymes, that are similar to enzymes associated with mammalian steroid synthesis.
      Perception and/or response mutants have also been identified via screening for
      altered sensitivity to BRs. Some of these mutants have been found to be defective
      in a leucine-rich repeat receptor kinase and in a component of a vacuolar ATPase.
      This review highlights the recent advances in unraveling BR synthesis/metabolism,
      transport, perception and response through the analysis of BR mutants.

PMID- 11230565
TI  - Quality control of photosystem II.
AB  - Photosystem II is particularly vulnerable to excess light. When illuminated with
      strong visible light, the reaction center D1 protein is damaged by reactive
      oxygen molecules or by endogenous cationic radicals generated by photochemical
      reactions, which is followed by proteolytic degradation of the damaged D1
      protein. Homologs of prokaryotic proteases, such as ClpP, FtsH and DegP, have
      been identified in chloroplasts, and participation of the thylakoid-bound FtsH in
      the secondary degradation steps of the photodamaged D1 protein has been
      suggested. We found that cross-linking of the D1 protein with the D2 protein, the
      alpha-subunit of cytochrome b(559), and the antenna chlorophyll-binding protein
      CP43, occurs in parallel with the degradation of the D1 protein during the
      illumination of intact chloroplasts, thylakoids and photosystem II-enriched
      membranes. The cross-linked products are then digested by a stromal protease(s).
      These results indicate that the degradation of the photodamaged D1 protein
      proceeds through membrane-bound proteases and stromal proteases. Moreover, a 33
      kDa subunit of oxygen-evolving complex (OEC), bound to the lumen side of
      photosystem II, regulates the formation of the cross-linked products of the D1
      protein in donor-side photoinhibition of photosystem II. Thus, various proteases
      and protein components in different compartments in chloroplasts are implicated
      in the efficient turnover of the D1 protein, thus contributing to the control of
      the quality of photosystem II under light stress conditions.

PMID- 11230566
TI  - An arabinogalactan protein(s) is a key component of a fraction that mediates
      local intercellular communication involved in tracheary element differentiation
      of zinnia mesophyll cells.
AB  - Local intercellular communication is involved in tracheary element (TE)
      differentiation of zinnia (Zinnia elegans L.) mesophyll cells and mediated by a
      proteinous macromolecule, which was designated xylogen. To characterize and
      isolate xylogen, a bioassay system to monitor the activity of xylogen was
      developed, in which mesophyll cells were embedded in microbeads of agarose gel at
      a low (2.0-4.3x10(4) cells ml(-1)) or high density (8.0-9.0x10(4) cells ml(-1))
      and microbeads of different cell densities were cultured together in a liquid
      medium to give a total density of 2.1-2.5x10(4) cells ml(-1). Without any
      additives, the frequency of TE differentiation was much smaller in the low
      density microbeads than in the high-density microbeads. This low level of TE
      differentiation in the low-density microbeads was attributable to the shortage of
      xylogen. When cultures were supplemented with conditioned medium (CM) prepared
      from zinnia cell suspensions undergoing TE differentiation, the frequency of TE
      differentiation in the low-density microbeads increased remarkably, indicating
      the activity of xylogen in the CM. The xylogen activity in CM was sensitive to
      proteinase treatments. Xylogen was bound to galactose-specific lectins such as
      Ricinus communis agglutinin and peanut agglutinin, and precipitated by beta
      glucosyl Yariv reagent. These results indicate that xylogen is a kind of
      arabinogalactan protein.

PMID- 11230567
TI  - High level expression of C4-specific NADP-malic enzyme in leaves and impairment
      of photoautotrophic growth in a C3 plant, rice.
AB  - The chloroplastic NADP-malic enzyme (NADP-ME) is a key enzyme of the C4
      photosynthesis pathway in NADP-ME type C4 plants such as maize. To express the
      chloroplastic NADP-ME in leaves of a C3 plant, rice, full-length cDNAs encoding
      the rice C3-specific isoform and the maize C4-specific isoform of the enzyme were
      expressed under the control of the rice CAB: promoter. Transformants carrying the
      rice cDNA showed the NADP-ME activities in the leaves less than several-fold that
      of non-transformants, while those carrying the maize cDNA showed activities up to
      30-fold that of non-transformants or about 60% of the NADP-ME activity of maize
      leaves. These results indicate that expression of the rice C3-specific NADP-ME is
      suppressed at co- and/or post-transcriptional levels by some regulation
      mechanisms intrinsic to rice, while that of the foreign C4-specific isoform can
      escape from such suppression. The accumulation of the maize C4-specific NADP-ME
      led to bleaching of leaf color and growth hindrance in rice plants under natural
      light. These deteriorative effects resulted from enhanced photoinhibition of
      photosynthesis due to an increase in the level of NADPH inside the chloroplast by
      the action of the maize enzyme.

PMID- 11230568
TI  - Transcriptional expression characteristics and subcellular localization of ADP
      glucose pyrophosphorylase in the oil plant Perilla frutescens.
AB  - Three ADP-glucose pyrophosphorylase clones were isolated from the cotyledon cDNA
      library of the oil plant, Perilla frutescens, and their intracellular
      localization investigated. Two of three cDNAs (PfagpS1 and PfagpS2) were
      homologous to the catalytic small subunit of AGPases found in other plants, while
      the third clone (PfagpL) was highly similar to the large subunit type.
      Transcripts for PfagpS1 and PfagpS2 were observed in both photosynthetic and non
      photosynthetic tissue, showing the highest expression in the stem, while PfagpL
      transcripts were abundantly expressed in stem and cotyledon. To evaluate the
      subcellular localization of PfagpS2 and PfagpL as well as the maize BT2, N
      terminus-GFP DNA fusion were constructed and transformed into tobacco plants.
      Immunoblot analysis showed that the expressed PfagpS2- and PfagpL-GFP fusions
      were targeted to the plastid in the heterologous tobacco system whereas the BT2
      GFP remained intact, suggesting a cytoplasmic location. These intracellular
      assignments were confirmed by direct confocal microscopic examination. GFP
      signals were localized to the cytoplasm as well as in the nucleus in BT2-GFP
      plants, and to the plastids in PfagpS2- and PfagpL-GFP plants. Our results
      indicate that Perilla cotyledons contain multiple AGPase subunits, of which at
      least two isoforms and very likely the third, are plastidial in nature.

PMID- 11230569
TI  - A new type of endo-xyloglucan transferase devoted to xyloglucan hydrolysis in the
      cell wall of azuki bean epicotyls.
AB  - A new type of xyloglucan-degrading enzyme was isolated from the cell wall of
      azuki bean (Vigna angularis Ohwi et Ohashi cv. Takara) epicotyls and its
      characteristics were determined. The enzyme was purified to apparent homogeneity
      by Concanavalin A (Con A)-Sepharose, cation exchange, and gel filtration columns
      from a cell wall protein fraction extracted with 1 M sodium chloride. The
      purified enzyme gave a single protein band of 33 kDa on SDS-PAGE. The enzyme
      specifically cleaved xyloglucans and showed maximum activity at pH 5.0 when
      assayed by the iodine-staining method. An increase in reducing power in
      xyloglucan solution was clearly detected after treatment with the purified
      enzyme. Xyloglucans with molecular masses of 500 and 25 kDa were gradually
      hydrolyzed to 5 kDa for 96 h without production of any oligo- or monosaccharide
      with the purified enzyme. The purified enzyme did not show an endo-type
      transglycosylation reaction, even in the presence of xyloglucan oligosaccharides.
      Partial amino acid sequences of the enzyme shared an identity with endo
      xyloglucan transferase (EXGT) family, especially with xyloglucan
      endotransglycosylase (XET) from nasturtium. These results suggest that the enzyme
      is a new member of EXGT devoted solely to xyloglucan hydrolysis.

PMID- 11230570
TI  - Isolation of cortical MTs from tobacco BY-2 cells.
AB  - We isolated the cortical microtubules (CMTs) from tobacco BY-2 cells to identify
      their components. By centrifugation of protoplasts homogenized in the presence of
      taxol, a MT-stabilizing reagent, in a density gradient of Percoll, we obtained
      membranous vesicles to which MTs forming a sheet-like bundle were attached.
      Rhodamine-conjugated Ricinus communis agglutinin I (RCA-I), a lectin that bound
      to the surface of protoplasts, stained these vesicles, indicating that they were
      plasma membrane (PM) vesicles that retained CMTs. CMTs were released by
      solubilization of PM vesicles with Triton X-100. A sheet-like array of CMTs was
      retained even after solubilization of PM vesicles. Immunoblot analysis of the
      isolated CMTs demonstrated the presence of tubulin, actin, the 65 kDa microtubule
      associated protein (MAP) and a 130 kDa RCA-I binding protein. Purification of the
      isolated CMTs by the temperature dependent disassembly-reassembly cycling method
      revealed four polypeptides, 190, 120, 85 and 65 kDa, co-assembling with CMTs.

PMID- 11230571
TI  - Isolation and RNA gel blot analysis of genes that could serve as potential
      molecular markers for leaf senescence in Arabidopsis thaliana.
AB  - Nine cDNAs, representing genes in which the transcripts accumulated in senescent
      leaves of Arabidopsis thaliana, were isolated by differential display reverse
      transcription polymerase chain reaction (DDRT-PCR) and the genes were designated
      yellow-leaf-specific gene 1 to 9 (YLS1-YLS9). Sequence analysis revealed that
      none of the YLS genes, except YLS6, had been reported as senescence-up-regulated
      genes. RNA gel blot analysis revealed that the transcripts of YLS3 accumulated at
      the highest level at an early senescence stage, whereas the transcripts from the
      other YLS genes reached their maximum levels in late senescence stages.
      Transcripts of YLS genes showed various accumulation patterns under natural
      senescence, and under artificial senescence induced by darkness, ethylene or ABA.
      These expression characteristics of YLS genes will be useful as potential
      molecular markers, which will enhance our understanding of natural and artificial
      senescence processes.

PMID- 11230572
TI  - Targeted disruption of psbX and biochemical characterization of photosystem II
      complex in the thermophilic cyanobacterium Synechococcus elongatus.
AB  - PSII-X is a small hydrophobic protein, which is universally present in
      photosystem II (PSII) core complex among cyanobacteria and plants. The role of
      PSII-X was studied by directed mutagenesis and biochemical analysis in the
      thermophilic cyanobacterium Synechococcus elongatus. The psbX-disrupted mutant
      could grow photoautotrophically indicative of non-essential function, while it
      showed growth defect under low CO(2) conditions. An active O(2)-evolving PSII
      complex was successfully isolated from the mutant and wild type. Protein
      composition of the isolated PSII complex was the same as wild type except for the
      absence of PSII-X. O(2) evolution supported by artificial quinones was affected
      in the psbX-disrupted mutant. At high concentration of 2,6-dichlorobenzoquinone
      or 2,6-dimethylbenzoquinone, the mutant showed much lower activity than wild
      type, while not much difference was found at low concentration. These results
      imply that binding or turnover of quinones at the Q(B) site depends, at least in
      part, on PSII-X protein in the PSII complex. Gel filtration chromatography of the
      PSII complex revealed that the dimeric structure of the complex was not greatly
      affected in the psbX-disrupted mutant.

PMID- 11230573
TI  - Physical arrangement of retrotransposon-related repeats in centromeric regions of
      wheat.
AB  - Cereal centromeres commonly contain many repetitive sequences that are derived
      from Ty3/gypsy retrotransposon. FISH analysis using a large DNA insert library of
      wheat identified a 67-kb clone (R11H) that showed strong hybridization signals on
      the centromeres. The R11H clone contains Ty3/gypsy retrotransposon-related
      sequences; both integrase and CCS1 family sequences were identified.
      Subsequently, we isolated additional 23 large-insert clones which also contained
      the integrase and CCS1 sequences. Based on the number of the integrase repeats in
      the clones determined by DNA gel blot analysis, we concluded that the
      retrotransposon-like sequences are tandemly repeated in wheat centromeres in ca.
      55-kb interval on average. This conclusion is consistent with the results of FISH
      analysis on the extended DNA fibers.

PMID- 11230574
TI  - RNA-dependent RNA polymerase activity associated with endogenous double-stranded
      RNA in rice.
AB  - RNA-dependent RNA polymerase (RdRp) activity was detected in the crude microsomal
      fraction of rice cultured cells that contain a 14 kbp double-stranded RNA
      (dsRNA). RdRp activity is maximal in the presence of all four nucleotide
      triphosphates and Mg2+ ion and is resistant to inhibitors of DNA-dependent RNA
      polymerases (actinomycin D and alpha-amanitin). RdRp activity increases
      approximately 2.5-fold in the presence of 0.5% deoxycholate. Treatment of
      purified microsomal fraction with proteinase K plus deoxycholate suggests that
      the RdRp enzyme complex with its own 14 kb RNA template is located in vesicles.
      The RdRp enzyme complex was solubilized with Nonidet P-40 and purified by
      glycerol gradient centrifugation, then exogenous RNA templates were added.
      Results indicate that exogenous dsRNA reduces RNA synthesis from the endogenous
      14 kb RNA template.

PMID- 11230575
TI  - Facile induction of apoptosis into plant cells associated with temperature
      sensitive lethality shown on interspecific hybrid from the cross Nicotiana
      suaveolens x N. tabacum.
AB  - Two lines of suspension culture cells were obtained from a hybrid seedling of
      Nicotiana suaveolens Lehm. x N. tabacum L. cv. Hicks-2 expressing temperature
      sensitive lethality. One of them (LH line) was inducible cell death in accordance
      with the lethality at 28 degrees C but not under high-temperature conditions (36
      degrees C). Another one (SH line) lost the lethality and survived at 28 degrees
      C. The cells of LH line showed apoptotic changes when they were cultured at 28
      degrees C. Fragmentation of nuclei was correlated with the lethality in the
      cells, as confirmed by fluorimetry of the nuclear DNA using laser scanning
      cytometry. Agarose gel analysis of DNA extracted from the cells expressing the
      lethality revealed a specific ladder pattern suggesting nucleosomal fragmentation
      that is one of the biochemical characteristics of apoptosis. From these facts, we
      confirmed that the process of cell death leading to hybrid lethality in the cells
      is certainly apoptosis. Hybrid cells were used in the experiments to estimate the
      point of no return in temperature-sensitive lethality and to examine the
      influence of cation in DNA fragmentation during apoptosis. The utility of hybrid
      cells as an experimental system for studies of hybrid lethality and apoptosis in
      plants was confirmed.

PMID- 11230576
TI  - Hyperosmotic stress induces a rapid and transient increase in inositol 1,4,5
      trisphosphate independent of abscisic acid in Arabidopsis cell culture.
AB  - Phospholipid metabolism is involved in hyperosmotic-stress responses in plants.
      To investigate the role of phosphoinositide-specific phospholipase C (PI-PLC)-a
      key enzyme in phosphoinositide turnover-in hyperosmotic-stress signaling, we
      analyzed changes in inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) content in
      response to hyperosmotic shock or salinity in Arabidopsis thaliana T87 cultured
      cells. Within a few s, a hyperosmotic shock, caused by mannitol, NaCl, or
      dehydration, induced a rapid and transient increase in Ins(1,4,5)P3. However, no
      transient increase was detected in cells treated with ABA. Neomycin and U73122,
      inhibitors of PI-PLC, inhibited the increase in Ins(1,4,5)P3 caused by the
      hyperosmotic shock. A rapid increase in phosphatidylinositol 4,5-bisphosphate
      (PtdIns(4,5)P2) in response to the hyperosmotic shock also occurred, but the rate
      of increase was much slower than that of Ins(1,4,5)P3. These findings indicate
      that the transient Ins(1,4,5)P3 production was due to the activation of PI-PLC in
      response to hyperosmotic stress. PI-PLC inhibitors also inhibited hyperosmotic
      stress-responsive expression of some dehydration-inducible genes, such as rd29A
      (lti78/cor78) and rd17 (cor47), that are controlled by the DRE/CRT cis-acting
      element but did not inhibit hyperosmotic stress-responsive expression of ABA
      inducible genes, such as rd20. Taken together, these results suggest the
      involvement of PI-PLC and Ins(1,4,5)P3 in an ABA-independent hyperosmotic-stress
      signal transduction pathway in higher plants.

PMID- 11230577
TI  - Inhibitors of ethylene synthesis inhibit auxin-induced stomatal opening in
      epidermis detached from leaves of Vicia faba L.
AB  - Using leaf epidermis from Vicia faba, we tested whether auxin-induced stomatal
      opening was initiated by auxin-induced ethylene synthesis. Epidermis was dark
      incubated in buffered KNO3 containing 0.1 mM alpha-napthalene acetic acid or 1 mM
      indole-3-acetic acid. Maximum net opening was ca. 4 micron after 6 h. Opening was
      reversed by 20 microM ABA, 0.1 mM CaCl2. 1-Aminocyclopropane carboxylic acid
      (ACC) synthase catalyzes synthesis of ACC, the immediate precursor to ethylene.
      Auxin-induced stomatal opening was fully inhibited by 10 microM 1
      aminoethoxyvinylglycine (AVG), an ACC synthase inhibitor. In solutions containing
      AVG, auxin-induced opening was restored in a concentration-dependent manner by
      exogenous ACC, but not in control solutions lacking an auxin. ACC-mediated
      reversal of AVG-inhibition of stomatal opening was inhibited by alpha
      aminoisobutyric acid (AIB), an inhibitor of ACC oxidase, the last enzyme in the
      ethylene biosynthetic pathway, by 10 microM silver thiosulfate (STS), an
      inhibitor of ethylene action, and by 20 microM ABA, 0.1 mM CaCl2. CoCl2, an
      inhibitor of ethylene synthesis, also inhibited auxin-induced opening. Both STS
      and CoCl2 inhibited opening induced by light or by fusicoccin, but neither light-
      nor fusicoccin-induced opening was inhibited by AVG. These results support the
      hypothesis that auxin-induced stomatal opening is mediated through auxin-induced
      ethylene production by guard cells.

PMID- 11230578
TI  - Novel family of sensor histidine kinase genes in Arabidopsis thaliana.
AB  - We identified three novel, highly homologous, sensor histidine kinases that
      possibly function in the plasma membrane of Arabidopsis thaliana, i.e. AHK2, 3
      and 4. While AHK2 and 3 are expressed in several organs, AHK4 is mainly expressed
      in roots. AHK3 suppresses a sensor histidine kinase mutant of yeast.

PMID- 11230579
TI  - Induction of PEP carboxylase and crassulacean acid metabolism by gibberellic acid
      in Mesembryanthemum crystallinum.
AB  - The induction of Crassulacean acid metabolism in M:esembryanthemum crystallinum
      was investigated in response to foliar application of gibberellic acid (GA).
      After 5 weeks of treatment, GA-treated plants showed 1.7- to almost a 4-fold
      increase of phosphoenolpyruvate carboxylase (PEPcase) activity with a concomitant
      increase in acid metabolism when compared to control plants. Immunoblot analysis
      indicated an increase in the PEPcase protein similar to that of salt treatment
      while Rubisco did not show a similar rise. The results indicate that exogenously
      applied GA accelerates plant developmental expression of PEPcase and Crassulacean
      acid metabolism in M: crystallinum.

PMID- 11230580
TI  - Cell wall integrity controls expression of endoxyloglucan transferase in tobacco
      BY2 cells.
AB  - Plant cells can monitor alternations in cell wall architecture. Treatment of
      tobacco BY2 cells with a cellulase or cellulose biosynthesis inhibitor
      significantly decreased the mRNA of endoxyloglucan transferase (EXGT). Our
      results indicated the importance of another gene(s) induced by cell wall defects
      for the decrease in EXGT mRNA.

PMID- 11230581
TI  - Improved salt tolerance of transgenic tobacco expressing apoplastic yeast-derived
      invertase.
AB  - We investigated the salt tolerance of transgenic tobacco, in which yeast
      invertase is expressed in the apoplastic (Apo-Inv) spaces. Whereas photosynthetic
      activities in wild-type tobacco in light were inhibited under salt stress,
      transgenic Apo-Inv tobacco maintained constant photosynthetic activities. The
      physical appearance of plants under salt stress also indicates that yeast
      invertase expression in the apoplastic space is beneficial for inducing salt
      tolerance. Apo-Inv tobacco had a much higher osmotic pressure increase in the
      cell sap than did wild-type tobacco under this type of stress. The physiological
      importance of sucrose metabolism under salt stress is discussed.

PMID- 11230582
TI  - Microstructural brain development after perinatal cerebral white matter injury
      assessed by diffusion tensor magnetic resonance imaging.
AB  - OBJECTIVE: Brain injury in premature infants is characterized predominantly by
      perinatally acquired lesions in the cerebral white matter (WM). The impact of
      such injury on the subsequent development of cerebral WM is not clear. This study
      uses diffusion tensor magnetic resonance imaging (MRI) to evaluate the effects of
      cerebral WM injury on subsequent microstructural brain development in different
      WM areas of the brain. METHODS: Twenty premature infants (gestational age: 29.1
      +/- 1.9 weeks) were studied by conventional MRI within the first 3 weeks of life
      and again at term, with the addition at the latter time of diffusion tensor MRI.
      Ten of the preterm infants had cerebral WM injury identified by the early MRI and
      were matched with 10 premature infants of similar gestational age and neonatal
      course but with normal neonatal MRI scans. Diffusion tensor MRI at term was
      acquired in coronal and axial planes and used to determine the apparent diffusion
      coefficient, a measure of overall restriction to water diffusion, and the
      relative anisotropy (RA), a measure of preferred directionality of diffusion, in
      central WM, anterior frontal WM, occipital WM, temporal WM, and the posterior
      limb of the internal capsule. Diffusion vector maps were generated from the
      diffusion tensor analysis to define the microstructural architecture of the
      cerebral WM regions. RESULTS: At term, the diffusion tensor MRI revealed no
      difference in apparent diffusion coefficient among preterm infants with or
      without perinatal WM lesions. By contrast, RA, the measure of preferred
      directionality of diffusion and thereby dependent on development of axonal fibers
      and oligodendroglia, was 25% lower in central WM, the principal site of the
      original WM injury. However, RA was unaffected in relatively uninjured WM areas,
      such as temporal, anterior frontal, and occipital regions. Notably, RA values in
      the internal capsule, which contains fibers that descend from the injured
      cerebral WM, were 20% lower in the infants with WM injury versus those without.
      Diffusion vector maps showed striking alterations in the size, orientation, and
      organization of fiber tracts in central WM and in those descending to the
      internal capsule. CONCLUSIONS: Perinatal cerebral WM injury seems to have major
      deleterious effects on subsequent development of fiber tracts both in the
      cerebral WM and more distally. The ultimate impact of brain injury in the newborn
      should be considered as a function not only of tissue destruction, but also of
      impaired subsequent brain development.

PMID- 11230583
TI  - Combined use of electroencephalogram and magnetic resonance imaging in full-term
      neonates with acute encephalopathy.
AB  - OBJECTIVE: The electroencephalogram (EEG) is widely used in full-term infants
      with acute neonatal encephalopathy, and its prognostic value has been confirmed
      by several studies. Magnetic resonance imaging (MRI) of the brain has also been
      applied in these patients, and increasing numbers of reports affirm its
      prognostic reliability. The aim of this study has been to investigate the
      correlation between an early EEG and MRI findings in infants with acute neonatal
      encephalopathy and to assess the prognostic value of a combination of EEG and MRI
      findings. PARTICIPANTS AND METHODS: Twenty-five full-term infants had an EEG
      recorded within the first 72 hours after birth and a neonatal brain MRI scan
      after the end of the first week. RESULTS: Both EEG and MRI were predictive of
      outcome. A normal MRI was always associated with normal EEG background activity
      and normal outcome and severe abnormalities on MRI with marked EEG abnormalities
      and an abnormal outcome. When the MRI showed moderate abnormalities, the EEG in
      all cases but one identified patients with normal and abnormal outcome.EEG, MRI,
      HIE, neurodevelopment.

PMID- 11230584
TI  - Hypocarbia in preterm infants with periventricular leukomalacia: the relation
      between hypocarbia and mechanical ventilation.
AB  - OBJECTIVE: The aim of this study was to elucidate the relationship between
      mechanical ventilation and hypocarbia in infants with periventricular
      leukomalacia (PVL). STUDY DESIGN: Matched pair analysis was conducted for 26
      infants with PVL and 26 with normal development, who were born between 27 and 32
      weeks' gestational age and required mechanical ventilation. The time-averaged
      carbon dioxide (CO(2)) index, PaCO(2), and pH were calculated every 24 hours for
      samples obtained from indwelling arterial catheters within the first 72 hours of
      life. The time-averaged respiratory rate of the ventilator (RR), peak inspiratory
      pressure (PIP), mean airway pressure (MAP), and ventilator index (VI) were also
      determined. The time-averaged total respiratory rate (TRR) was determined by
      observing the movement of the chest wall. The patients' characteristics,
      antenatal and neonatal variables, and electroencephalographic findings were also
      compared. RESULTS: The time-averaged CO(2) index was larger, the time-averaged
      CO(2) lower and the time-averaged pH higher in infants with PVL than in those
      with normal development on the third day of life. There was no significant
      difference in the time-averaged RR, PIP, MAP, or VI on any day. TRR was larger in
      the PVL group than in the control group on each day, but there was no significant
      difference. No significant difference was observed in the clinical
      characteristics or neonatal variables. Electroencephalographic abnormalities
      within 48 hours of life were more frequent in infants with PVL than in those with
      normal development. CONCLUSION: Hypocarbia was associated with PVL because the
      time-averaged CO(2) index was larger and the time-averaged PaCO(2) lower in
      infants with PVL than in those with normal development. However, the ventilator
      settings were similar among the infants with and without PVL.

PMID- 11230585
TI  - Neurologic outcomes of 90 neonates and infants with persistent hyperinsulinemic
      hypoglycemia.
AB  - OBJECTIVE: To evaluate the neurologic outcomes of neonates and infants suffering
      from persistent hyperinsulinemic hypoglycemia of infancy (PHHI). METHODS: The
      neurologic development of 90 PHHI patients was studied retrospectively. Sixty
      three patients were treated surgically and 27 were treated medically. Fifty-four
      patients were neonates, of whom 8 were treated medically and 46 were operated on
      (19 for a focal adenomatous hyperplasia and 27 for diffuse hyperinsulinism).
      Thirty-six patients had infancy-onset hyperinsulinism, of whom 19 were treated
      medically and 17 underwent pancreatectomy (10 patients for a focal adenomatous
      hyperplasia and 7 for diffuse hyperinsulinism). RESULTS: Severe psychomotor
      retardation was found in 7 patients, 6 with neonatal-onset PHHI. Intermediate
      psychomotor disability existed in 12 patients; epilepsy existed in 16. Neonatal
      onset was the main risk factor for severe retardation or epilepsy. Medically
      treated patients were less severely affected than those treated by surgery, and
      there was no difference between the diffuse and focal forms of hyperinsulinism.
      CONCLUSION: Neonatal hyperinsulinemic hypoglycemia is still a severe disease with
      an important risk to rapidly develop severe mental retardation and epilepsy.

PMID- 11230586
TI  - Neurodevelopmental outcome of infants treated with head cooling and mild
      hypothermia after perinatal asphyxia.
AB  - OBJECTIVES: To determine the neurodevelopmental outcome of infants treated with
      head cooling with systemic hypothermia after hypoxic-ischemic encephalopathy.
      STUDY DESIGN: Infants >/=37 weeks' gestation, who had an umbilical artery pH
      </=7.09 or Apgar score </=6 at 5 minutes, plus clinical encephalopathy. Infants
      with major congenital abnormalities were excluded. TRIAL DESIGN: Infants were
      allocated to either no cooling (rectal temperature = 37.0 +/- 0.2 degrees C, n =
      15), or, sequentially, to head cooling accompanied by different levels of
      systemic hypothermia, including minimal cooling, rectal temperature 36.5 degrees
      C to 36 degrees C (n = 6), and mild cooling, to either 35.9 degrees C to 35.5
      degrees C (n = 6), 35 +/- 0.5 degrees C (n = 6) or 34.5 +/- 0.5 degrees C (n =
      7). Head cooling was accomplished by circulating cooled water through a coil of
      tubing wrapped around the head for up to 72 hours. Survivors were followed up
      with regular neurologic examination by a neonatologist until 18 months of age,
      then with blinded developmental testing using the revised Bayley Scales. RESULTS:
      A total of 40 term infants were enrolled from 2 to 5 hours after birth. The
      control and the cooled groups were not significantly different for gestation,
      birth weight, Apgar score, and initial pH. There were 6 early neonatal deaths (3
      normothermic and 3 cooled), and 1 death in infancy associated with severe spastic
      cerebral palsy in a normothermic infant. Six normothermic, 1 minimally cooled,
      and 4 mildly cooled infants had early stage 1 encephalopathy; all but 1 had a
      good outcome. Among infants with early stage 2 or 3 encephalopathy, an adverse
      outcome was found in 4 of 9 normothermic infants (44%) and 4 of 5 minimally
      cooled infants (80%), whereas in the combined mildly cooled groups, an adverse
      outcome was found in 4 of 15 infants (26%, odds ratio 0.46 [0.08, 2.56] vs
      normothermia). CONCLUSIONS: The present study supports the safety of hypothermia,
      with no evidence of late adverse effects in any infant. Among infants with
      moderate to severe encephalopathy at enrollment, there was a tendency toward
      better outcome. These results emphasize the relatively wide range of outcomes
      using purely clinical criteria for enrollment. Therapeutic hypothermia should not
      be used outside of stringent, multicenter trials.

PMID- 11230587
TI  - Adolescent suicide attempts: risks and protectors.
AB  - OBJECTIVE: In 1997, suicide was the third leading cause of death among 10- to 19
      year-olds in the United States, with the greatest increases in suicide rates in
      the previous decade experienced by black and other minority youth. The purpose of
      this study was to identify risk and protective factors for suicide attempts among
      black, Hispanic, and white male and female adolescents. METHODS: We used data
      from the National Longitudinal Study of Adolescent Health, conducted in 1995 and
      1996. A nationally representative sample of 13 110 students in grades 7 through
      12 completed 2 in-home interviews, an average of 11 months apart. We examined
      Time 1 factors at the individual, family, and community level that predicted or
      protected against Time 2 suicide attempts. RESULTS: Perceived parent and family
      connectedness was protective against suicide attempts for black, Hispanic, and
      white girls and boys, with odds ratios ranging from 0.06 to 0.32. For girls,
      emotional well-being was also protective for all of the racial/ethnic groups
      studied, while a high grade point average was an additional protective factor for
      all of the boys. Cross-cutting risk factors included previous suicide attempt,
      violence victimization, violence perpetration, alcohol use, marijuana use, and
      school problems. Additionally, somatic symptoms, friend suicide attempt or
      completion, other illicit drug use, and a history of mental health treatment
      predicted suicide attempts among black, Hispanic, and white females. Weapon
      carrying at school and same-sex romantic attraction were predictive for all
      groups of boys. Calculating the estimated probabilities of attempting suicide for
      adolescents with increasing numbers of risk and protective factors revealed that
      the presence of 3 protective factors reduced the risk of a suicide attempt by 70%
      to 85% for each of the gender and racial/ethnic groups, including those with and
      without identified risk factors. CONCLUSIONS: In these national samples of black,
      Hispanic, and white youth, unique and cross-cutting factors derived from a
      resiliency framework predicted or protected against attempting suicide. In
      addition to risk reduction, promotion of protective factors may offer an
      effective approach to primary as well as secondary prevention of adolescent
      suicidal behavior.

PMID- 11230588
TI  - Association of plasma cortisol and chronic lung disease in preterm infants.
AB  - BACKGROUND: It has been suggested that preterm infants may have developmental
      immaturity of the hypothalamic-pituitary-adrenal axis, and that decreased
      cortisol response to stress increases risk of chronic lung disease (CLD)
      secondary to inflammatory lung injury. METHODS: To investigate the relationship
      between endogenous corticosteroid and CLD, we measured plasma cortisol during the
      first 28 days of life in a subset of neonates in the North American Thyrotropin
      Releasing Hormone (TRH) Collaborative Trial. Analyses were performed on 314
      infants, 24 to 32 weeks' gestation, whose mothers received 1 or 2 courses of
      antenatal corticosteroids plus TRH or placebo. RESULTS: Mean cortisol was 3.1
      microg/dL (range: 0.1-17.9) at birth, reached maximal levels at 24 hours (19.4
      microg/dL, range: 0.8-124.6), and decreased to 5.9 microg/dL (range: 0.2-24.7) at
      14 to 28 days of age; levels during the first week were not associated with
      gestational age. The Clinical Risk Index for Babies (CRIB), a neonatal assessment
      tool that is correlated with risk of mortality, was positively associated with
      cortisol level on days 1 and 3 through 7. TRH versus placebo treatment did not
      influence cortisol levels at any time point. To examine the relationship between
      cortisol and adverse outcome of death or CLD at 36 weeks' postmenstrual age
      (CLD36), logistic regression models adjusting for known contributing clinical
      factors (gestational age and CRIB score) were fit. There was a statistically
      borderline negative association between median cortisol level at 3 to 7 days and
      CLD36. After adjusting for gestational age and CRIB score, the predicted
      probability of CLD36 was only minimally influenced by the cortisol concentration.
      CONCLUSION: In preterm infants, basal plasma cortisol concentration during the
      first week is a weak predictor for CLD36. Possible benefits as well as risks of
      supplemental, low-dose cortisol treatment of high-risk preterm infants remain to
      be determined.

PMID- 11230589
TI  - Excess risk of severe acute illness in children with chronic health conditions.
AB  - We estimated the relative risk (RR) of an unscheduled pediatric intensive care
      unit (ICU) admission as a marker for severe acute illness in children with
      chronic health conditions, compared with previously healthy children. Potentially
      preventable events that lead to acute illness were identified to develop
      preventive strategies. METHODS: Children with chronic conditions were defined as
      those who have a chronic physical, developmental, behavioral, or emotional
      condition and who also require health and related services of a type or amount
      beyond that required by children generally. RR was estimated from admissions and
      regional population data. Potentially preventable events that lead to ICU
      admission of chronically ill children were identified retrospectively from
      hospital records. RESULTS: Children with chronic health conditions had an RR of
      3.3 for an unscheduled ICU admission related to their chronic condition, compared
      with previously healthy individuals (95% confidence interval [CI] = 2.5-4.2). The
      risk of severe acute illness in the small subgroup that received technology
      assisted care was much greater (RR = 373; 95% CI = 330-422) than for the large
      group of chronically ill patients who did not require technology-assisted care
      (RR = 2.3; 95% CI = 1.7-3.0), each expressed relative to previously healthy
      children. Acute illness related to chronic health conditions accounted for 45% of
      251 unscheduled ICU admissions during the 1-year study. Thirty-two percent of
      admissions that were related to chronic conditions were judged to have been
      potentially preventable. Preventable events were more common for those who did
      not require technology-assisted care, occurring in 38% of admissions, compared
      with those who received technology-assisted care, for whom 19% of admissions
      involved a preventable event. Fifty-six percent of potentially preventable events
      involved the physical or social environment and decisions made by the family,
      whereas 64% could be attributed to health care system factors. CONCLUSIONS:
      Children with chronic health conditions account for a substantial share of severe
      acute illness in a region. Because their underlying conditions have already been
      identified, problems may be anticipated. The small number of children who receive
      technology-assisted care each have such a high risk of severe and unavoidable
      acute illness that individualized emergency care plans are justified. For the
      remainder of children with chronic conditions, investigation of health system
      strategies to improve families' ability to anticipate, minimize, or prevent
      related acute illness is warranted.

PMID- 11230591
TI  - Relation of two different subtypes of croup before age three to wheezing, atopy,
      and pulmonary function during childhood: a prospective study.
AB  - OBJECTIVE: Some retrospective evidence suggests that children with a history of
      croup may be at increased risk of subsequently developing asthma, atopy, and
      diminished pulmonary function. The objective of this study was to determine the
      long-term outcome of croup (as diagnosed by a physician) in early life. METHODS:
      Lower respiratory illnesses (LRIs) in the first 3 years of life were assessed in
      884 children who were enrolled in a large longitudinal study of airway diseases
      at birth. Pulmonary function tests, markers of atopy, and wheezing episodes were
      studied at different ages between birth and 13 years. RESULTS: Ten percent of
      children had croup with wheeze (Croup/Wheeze), 5% had croup without wheeze
      (Croup/No Wheeze), 36% had another LRI (Other LRI), and 48% had no LRI.
      Respiratory syncytial virus was more frequently isolated in children with
      Croup/Wheeze and Other LRI than in those with Croup/No Wheeze. There was no
      association between croup in early life and markers of atopy measured during the
      school years. Only children with Croup/Wheeze and with Other LRI had a
      significant risk of subsequent persistent wheeze later in life. Significantly
      lower levels of indices of intrapulmonary airway function were observed at ages
      <1 (before any LRI), 6, and 11 years in children with Croup/Wheeze and Other LRI
      compared with children with No LRI. Conversely, inspiratory resistance before any
      LRI episode was significantly higher in infants who later developed Croup/No
      Wheeze than in the other 3 groups. CONCLUSIONS: We distinguish 2 manifestations
      of croup with and without wheezing. Children who present with croup may or may
      not be at increased risk of subsequent recurrent lower airway obstruction,
      depending on the initial lower airway involvement, and preillness and postillness
      abnormalities in lung function associated with this condition.

PMID- 11230590
TI  - Residential exposures associated with asthma in US children.
AB  - OBJECTIVE: Residential exposures are recognized risk factors for childhood
      asthma, but the relative contribution of specific risk factors and the overall
      contribution of housing to asthma in US children is unknown. The objective of
      this study was to identify risk factors and estimate the population attributable
      risk of residential exposures for doctor-diagnosed asthma for US children.
      METHODS: A cross-sectional survey was conducted from 1988 to 1994. Survey
      participants were 8257 children who were <6 years old and who participated in the
      Third National Health and Nutrition Examination Survey, a survey of the health
      and nutritional status of children and adults in the United States. The main
      outcome measure was doctor-diagnosed asthma, as reported by the parent. RESULTS:
      Six percent of children had doctor-diagnosed asthma. The prevalence of asthma was
      higher among boys (6.7%) than girls (5.1%) and was higher among black children
      (8.9%) than white children (5.2%). Risk factors for doctor-diagnosed asthma
      included a family history of atopy (odds ratio [OR]: 2.2; 95% confidence interval
      [CI]: 1.5, 3.1), child's history of allergy to a pet (OR: 24.2; 95% CI: 8.4,
      69.5), exposure to environmental tobacco smoke (OR: 1.8; 95% CI: 1.2-2.6), use of
      a gas stove or oven for heat (OR: 1.8; 95% CI: 1.02-3.2), and presence of a dog
      in the household (OR: 1.6; 95% CI: 1.1, 2.3). The population attributable risk of
      >/=1 residential exposure for doctor-diagnosed asthma in US children <6 years old
      was 39.2%, or an estimated 533 000 excess cases, whereas having a family history
      of atopy accounted for 300 000. The attributable cost of asthma as a result of
      residential exposures for children <6 years old was $402 million (95% CI: $296
      $507 million) annually. CONCLUSIONS: The elimination of identified residential
      risk factors, if causally associated with asthma, would result in a 39% decline
      in doctor-diagnosed asthma among US children <6 years old.

PMID- 11230592
TI  - Analysis of nonsteroidal antiinflammatory drugs in meconium and its relation to
      persistent pulmonary hypertension of the newborn.
AB  - OBJECTIVE: The objective of this study was to detect fetal exposure to
      nonsteroidal antiinflammatory drugs (NSAIDs) by meconium analysis and to
      determine the relationship between fetal exposure to NSAIDs and the development
      of persistent pulmonary hypertension of the newborn (PPHN). METHODS: In a case
      control study of the inborn and outborn nurseries of a large urban medical
      center, meconium was collected from 101 newborn infants (40 with the diagnosis of
      PPHN based on clinical or echocardiographic criteria and 61 randomly selected,
      healthy, term infants [control]) and analyzed for NSAIDs (ibuprofen, naproxen,
      indomethacin, and aspirin) by gas chromatography/mass spectrometry. The risk of
      developing PPHN was determined in infants who were exposed antenatally to NSAID.
      RESULTS: Infants with PPHN (n = 40) had a mean gestation of 38.9 weeks and birth
      weight of 3524 g, which were similar to the those of the control group (n = 61).
      However, the incidence of low Apgar scores (</=6) at 1 minute and 5 minutes was
      significantly higher in the PPHN group than in the control group. The diagnoses
      associated with PPHN were primary PPHN (25%), meconium aspiration syndrome (35%),
      respiratory distress syndrome (20%), low Apgar score/asphyxia (12.5%), and
      pneumonia/sepsis (8%). Mean duration of ventilator support for the PPHN group was
      11 days. Nitric oxide (NO) was given to 19 infants (47.5%) for a mean duration of
      25.4 hours. Fourteen of the 19 infants who were treated with NO (74%) required
      extracorporeal membrane oxygenation, and 2 died. The overall incidence of
      positive NSAID in meconium in the study population (n = 101) was 49.5%: 22.8%
      were positive for ibuprofen, 18.8% for naproxen, 7.9% for indomethacin, and 43.6%
      for aspirin. There was poor agreement (Cohen's kappa = 0.09) between maternal
      history of NSAID use and NSAID detection in meconium. PPHN was significantly
      associated with 1) the presence of at least 1 NSAID in meconium (odds ratio [OR]
      = 21.47; 95% confidence interval [CI] = 7.12-64.71) or 2) the presence in
      meconium of aspirin (OR = 8.09; 95% CI = 3.27-20.10), ibuprofen (OR = 12.89; 95%
      CI 3.93-42.32), or naproxen (OR = 3.31; 95% CI = 1.17-9.33). By logistic
      regression analysis, low Apgar scores at 1 and 5 minutes and the antenatal
      exposure to aspirin, naproxen, and ibuprofen were significantly associated with
      PPHN and treatment with inhaled NO or extracorporeal membrane oxygenation.
      CONCLUSION: We confirm by meconium analysis the results of previous studies that
      demonstrated that the use of NSAIDs during pregnancy, particularly aspirin,
      ibuprofen, and naproxen, is high; is grossly underestimated by maternal history;
      and is significantly associated with PPHN. Thus, the easy access to over-the
      counter NSAIDs of pregnant women should be reevaluated, and the potential dangers
      of these drugs to the newborn infant should be more effectively promoted.

PMID- 11230593
TI  - Association of lower continuity of care with greater risk of emergency department
      use and hospitalization in children.
AB  - CONTEXT: The benefits of continuity of pediatric care remain controversial.
      OBJECTIVE: To determine whether there is an association between having a
      continuous relationship with a primary care pediatric provider and decreased risk
      of emergency department (ED) visitation and hospitalization. DESIGN:
      Retrospective cohort study. Setting and Population. We used claims data from 46
      097 pediatric patients enrolled at Group Health Cooperative, a large staff-model
      health maintenance organization, between January 1, 1993, and December 31, 1998,
      for our analysis. To be eligible, patients had to have been continuously enrolled
      for at least a 2-year period or since birth and to have made at least 4 visits to
      one of the Group Health Cooperative clinics. MAIN EXPOSURE VARIABLE: A continuity
      of care (COC) index that quantifies the degree to which a patient has experienced
      continuous care with a provider. MAIN OUTCOME MEASURES: ED utilization and
      hospitalization. RESULTS: Compared with children with the highest COC, children
      with medium continuity were more likely to have visited the ED (hazard ratio
      [HR]: 1.28 [1.20-1.36]) and more likely to be hospitalized (HR: 1.22 [1.09
      1.38]). Children with the lowest COC were even more likely to have visited the ED
      (HR: 1.58 [1.49-1.66]) and to be hospitalized (HR: 1.54 [1.33-1.75]). These risks
      were even greater for children on Medicaid and those with asthma. CONCLUSIONS:
      Lower continuity of primary care is associated with higher risk of ED utilization
      and hospitalization. Efforts to improve and maintain continuity may be warranted.

PMID- 11230594
TI  - Sudden infant death syndrome, bedsharing, parental weight, and age at death.
AB  - OBJECTIVE: To assess the role of parental bedsharing in sudden infant death
      syndrome (SIDS)-like deaths, this study examines the hypothesis that, compared
      with other SIDS cases, the age distribution of deaths associated with bedsharing
      should be lower in younger, less vigorous infants. METHODS: For 84 SIDS cases in
      Cleveland, Ohio, 1992 to 1996, age at death, maternal weight, and other risk
      factors for SIDS were compared for cases grouped according to bedsharing status.
      RESULTS: Mean ages at death were 9.1 weeks for 30 bedsharing and 12.7 for 54
      nonbedsharing cases, counting 10 with missing information as nonbedsharing. Mean
      pregravid weights of bedsharing mothers exceeded those of nonbedsharing mothers
      (84.1 vs 67.0 kg). Mean ages at death for nonbedsharing infants, bedsharing
      infants of smaller mothers, and bedsharing infants of larger mothers were 12.7,
      10.3, and 7.6 weeks, respectively. Large maternal size did not affect age at
      death in the absence of bedsharing. CONCLUSIONS: By demonstrating that among an
      urban population at high risk for SIDS, bedsharing is strongly associated with a
      younger age at death, independent of any other factors, this study provides
      evidence of a relationship between some SIDS-like deaths and parent-infant
      bedsharing, particularly if the parent is large.

PMID- 11230595
TI  - Back to sleep: good advice for parents but not for hospitals?
AB  - BACKGROUND: In October 1998, when we surveyed nurses working in Iowa obstetric
      units about infant sleeping position in the hospital and recommendations for
      infant sleeping position at home, we learned that the side position was used
      frequently in the hospital and also was considered to be an acceptable
      alternative for sleeping position at home. OBJECTIVE: The purpose of our present
      study was to determine why nurses continued to use and endorse the side sleeping
      position rather than the supine position. DESIGN: We surveyed all Iowa hospitals
      that had an obstetric service as of July 1999 to learn why the side position was
      used. RESULTS: All 94 hospitals with obstetric services responded to the survey
      and revealed that 2 major factors were considered when an infant was put to sleep
      on his/her side. The most frequent response was fear of aspiration (57 responses
      or 51.4%) and the second was adherence to a federal brochure that lists side
      sleeping as a reasonable alternative (38 responses or 34.2%). CONCLUSION: We
      conclude that the reasons reported for use of the side position in Iowa maternity
      hospitals do not justify its continuing use. We believe that information about
      the importance of placing an infant on his/her back to sleep and its superiority
      over placing an infant on his/her side to sleep is sufficient to warrant its
      availability in every maternity hospital. We speculate that if the infant
      sleeping position used in the hospital is not different from that taught to
      parents, there will be less parental confusion and greater adherence to infant
      positioning shown to reduce sudden infant death syndrome.

PMID- 11230596
TI  - Environmental tobacco smoke and serum vitamin C levels in children.
AB  - BACKGROUND: High levels of free radicals in tobacco smoke are thought to be
      responsible for decreased levels of serum ascorbic acid in smokers and adults
      exposed to environmental tobacco smoke (ETS). The association of ETS to serum
      ascorbic acid in children is unknown. METHODS: Data were analyzed from the Third
      National Health and Nutrition Examination Survey, a nationally representative
      sample of children and adolescents (n = 2968). Comprehensive data including serum
      cotinine levels and family smoking patterns allowed for analysis of relationship
      of ETS to serum ascorbic acid levels. Data from 24-hour dietary recall also
      allowed for the control of vitamin C intake. Children were divided into
      categories of low and high ETS exposure based on levels of serum cotinine above
      or below 2 ng/mL. Smokers were defined by either self-report or serum cotinine
      >15 ng/mL. RESULTS: Although there was a trend for lower levels of vitamin C
      intake in children with higher levels of ETS exposure, this trend did not reach
      statistical significance. Among all children, serum ascorbic acid levels were
      linearly related to serum cotinine levels (r = 0.19). In addition, a dose
      response relationship was observed between levels of tobacco exposure and serum
      ascorbic acid levels. After adjusting for age, gender, vitamin C intake, and
      multivitamin use, environmental tobacco exposure remained significantly
      associated with lower levels of serum ascorbic acid in children who were exposed
      to both high and low levels of ETS. CONCLUSION: Exposure of children to ETS leads
      to significant alterations in serum ascorbic acid levels. Therefore, this study
      further highlights the potential dangers of ETS to children.

PMID- 11230597
TI  - The timing and predictors of the early termination of breastfeeding.
AB  - OBJECTIVE: To determine the prevalence and correlates of the early
      discontinuation of breastfeeding by mothers eligible for the Women, Infants, and
      Children Program (WIC). METHODOLOGY: A longitudinal observational study in which
      we enrolled English-speaking mothers who initiated breastfeeding after delivering
      healthy-term infants at Yale-New Haven Hospital and planned to bring their
      infants to the hospital's primary care center. Data on mother's baseline
      knowledge, attitudes, beliefs, and problems regarding breastfeeding were
      collected by semistructured interviews within 48 hours after delivery, at 1 and 2
      weeks' postpartum, and by chart reviews at 2 and 4 months. A nonparticipating
      control group was used to test the Hawthorne effect. RESULTS: Of the 64
      participating mothers, the majority were minority (56% black, 34% of Puerto Rican
      origin), single (75%), and already enrolled in WIC (91%). The rates of
      discontinuation of breastfeeding were 27%, 37%, 70%, and 89% by 1 week, 2 weeks,
      2 months, and 4 months, respectively. The mother's knowledge and problems of
      lactation were not associated with the early discontinuation of breastfeeding.
      After using logistic regression to control for potential confounders, mothers who
      lacked confidence at baseline that they would still be breastfeeding at 2 months
      (risk ratio: 2.38, 95% confidence interval: 1.82-6.18), and those who believed
      that the baby prefers formula (risk ratio: 1.68, 95% confidence interval: 1.04
      2.71) were more likely to stop breastfeeding within the first 2 weeks postpartum.
      CONCLUSIONS: The results of this study demonstrate that interventions aimed at
      prolonging the duration of breastfeeding in this population will need to shift
      focus from increasing knowledge and managing problems of lactation to enhancing
      the mother's confidence regarding breastfeeding, while also addressing beliefs
      regarding an infant's preferences.

PMID- 11230598
TI  - International experience with trisomy 21 infants placed on extracorporeal
      membrane oxygenation.
AB  - OBJECTIVE: To characterize the international experience concerning neonates with
      trisomy 21 (T21) managed with extracorporeal membrane oxygenation (ECMO), and to
      compare and contrast this group of patients to the neonatal ECMO population as a
      whole. METHODS: Data from the Extracorporeal Life Support Organization for
      newborn infants placed on ECMO between January 1984 and June 1999 were analyzed.
      Infants with T21 were compared with the group of infants without T21. RESULTS:
      Fifteen thousand nine hundred forty-six infants, including 91 (n = 91) with the
      diagnosis of T21, were placed on ECMO for neonatal respiratory failure during the
      14.5-year period. T21 infants were overrepresented in the ECMO population by
      several-fold when compared with the incidence of T21 in the general population.
      Eighty-seven of the 91 T21 infants were placed on ECMO after 1989. The
      distribution of primary diagnoses leading to ECMO differed between the groups
      (T21 vs non-T21): primary persistent pulmonary hypertension, 47.3% versus 13%;
      meconium aspiration syndrome, 23.1% versus 32.9%; sepsis, 7.7% versus 13.2%;
      congenital diaphragmatic hernia, 7.7% versus 19.9%; and respiratory distress
      syndrome, 3.3% versus 7.9%. Although survival to discontinuation of ECMO was
      similar in the 2 groups, likelihood of survival to discharge was decreased for
      T21 infants (65.9% vs 75.6%) because of increased post-ECMO mortality.
      CONCLUSIONS: Extracorporeal Life Support Organization registry data suggests that
      T21 infants are at a significantly higher risk of being placed on ECMO for
      neonatal respiratory failure than the general population, perhaps as a result of
      delayed extrauterine pulmonary vascular adaptation, as manifested in the high
      rate of primary persistent pulmonary hypertension as the primary diagnosis. There
      may have been a shift in attitude regarding the use of ECMO in the T21 patient
      after 1989. Although most T21 patients placed on ECMO will survive, the prognosis
      is more guarded in this population when compared with all infants so managed. The
      long-term neurodevelopmental outcome of this group of T21 ECMO survivors is
      currently unknown.

PMID- 11230599
TI  - Postgraduate education for pediatricians.

PMID- 11230600
TI  - The testing of antihypertensive medications in children: report of the
      Antihypertensive Agent Guidelines Subcommittee of the Pediatric Pharmacology
      Research Units.

PMID- 11230602
TI  - The road to primary prevention of lead toxicity in children.

PMID- 11230601
TI  - Contraception in the adolescent: an update.
AB  - Contraception remains an important part of national efforts to reduce adolescent
      pregnancy in the United States. A number of safe and effective contraceptive
      methods are available for our youth, including abstinence, barrier methods, oral
      contraceptives, Depo-Provera, and Norplant. Research over the past few decades
      has resulted in a variety of oral contraceptives with reduced amounts of hormones
      and reduced side-effects. A number of methods have received approval by the Food
      and Drug Administration since the last review in 1980, including emergency
      contraceptives, depomedroxyprogesterone acetate, and the cervical cap. The use of
      condoms and vaginal spermicides continues to be recommended for all sexually
      active adolescents to reduce (not eliminate) the risk for acquiring sexually
      transmitted diseases. A polyurethane condom is now available, in addition to the
      latex condom and other barrier contraceptives, including the following:
      diaphragm, cervical cap, vaginal sponge, female condom and vaginal spermicides.
      Because of continuing concerns about pelvic inflammatory disease related to
      intrauterine devices, currently available intrauterine devices are not
      recommended for most adolescents. Abortion is not considered as a contraceptive
      method.

PMID- 11230603
TI  - Physicians and breastfeeding promotion in the United States: a call for action.

PMID- 11230604
TI  - Predicting the future for term infants experiencing an acute neonatal
      encephalopathy: electroencephalogram, magnetic resonance imaging, or crystal
      ball?

PMID- 11230605
TI  - Asthma clinical pathways: toward what end?

PMID- 11230606
TI  - The necessity and difficulty of conducting magnetic resonance imaging studies on
      infant brain development.

PMID- 11230607
TI  - Continuous infusion of glucagon induces severe hyponatremia and thrombocytopenia
      in a premature neonate.
AB  - We report on a 35-week gestation infant who developed severe hyponatremia and
      thrombocytopenia after continuous infusion of glucagon for the treatment of
      intractable hypoglycemia. Given these serious side effects,glucagon infusion
      should be avoided in the treatment of premature infants.hypoglycemia, glucose,
      small for gestational age. Hypoglycemia is commonly seen in premature infants,
      and the provision of a standard glucose intake is often not sufficient to
      maintain euglycemia. For these infants, an increase in glucose infusion to
      provide 4 to 8 mg/kg/min is initially recommended.1 Should this approach fail,
      pharmacologic agents such as corticosteroids or diazoxide are indicated.1 When
      the serum glucose in premature or small for gestational age infants cannot be
      adequately maintained, a glucagon infusion is now suggested as the best treatment
      approach.2,3 We report the use of glucagon infusion for the treatment of severe
      hypoglycemia in a premature infant. A severe hyponatremia associated with
      transient convulsions and thrombocytopenia was observed in the neonate after
      treatment. Discontinuation of the glucagon infusion resulted in prompt resolution
      of these abnormalities.

PMID- 11230608
TI  - American Academy of Pediatrics: Counseling families who choose complementary and
      alternative medicine for their child with chronic illness or disability.
      Committee on Children With Disabilities.
AB  - The use of complementary and alternative medicine (CAM) to treat chronic illness
      or disability is increasing in the United States. This is especially evident
      among children with autism and related disorders. It may be challenging to the
      practicing pediatrician to distinguish among accepted biomedical treatments,
      unproven therapies, and alternative therapies. Moreover, there are no published
      guidelines regarding the use of CAM in the care of children with chronic illness
      or disability. To best serve the interests of children, it is important to
      maintain a scientific perspective, to provide balanced advice about therapeutic
      options, to guard against bias, and to establish and maintain a trusting
      relationship with families. This statement provides information and guidance for
      pediatricians when counseling families about CAM.

PMID- 11230609
TI  - American Academy of Pediatrics: Technical report: Alternative dispute resolution
      in medical malpractice.
AB  - The purpose of this technical report is to provide pediatricians with an
      understanding of past crises within the professional liability insurance
      industry, the difficulties of the tort system, and alternative strategies for
      resolving malpractice disputes that have been applied to medical malpractice
      actions. Through this report, pediatricians will gain a technical understanding
      of common alternative dispute resolution (ADR) strategies. The report explains
      the distinctions between various ADR methods in terms of process and outcome,
      risks and benefits, appropriateness to the nature of the dispute, and long-term
      ramifications. By knowing these concepts, pediatricians faced with malpractice
      claims will be better-equipped to participate in the decision-making with legal
      counsel on whether to settle, litigate, or explore ADR options.

PMID- 11230610
TI  - Minimizing false-positives in universal newborn hearing screening: a simple
      solution.
AB  - BACKGROUND AND OBJECTIVES: The false-positive rates of previously reported
      universal newborn hearing screening (UNHS) programs range between 2.5% and 8%.
      Critics of UNHS programs have claimed that this rate is too high and might lead
      to a number of the negative effects produced by false-positive screening tests,
      namely emotional trauma, disease labeling, iatrogenesis from unnecessary testing,
      and increased expense in terms of time and money. We previously reported, based
      on some preliminary data, that as many as 80% of newborns who failed the initial
      hearing screen subsequently passed when they were retested the following day,
      before being discharged from the hospital. We now present the results of this
      intervention for our entire UNHS program during a 7-month period. METHODS: We
      analyzed data from 3142 non-neonatal intensive care unit infants screened with an
      automated auditory brainstem response at the Women's Hospital of Greensboro from
      November 1, 1999 to May 31, 2000. A protocol was developed wherein all infants
      who failed the initial UNHS were rescreened with another automated auditory
      brainstem response before hospital discharge. Data collected included pass/fail
      rates during the inpatient stay as well as follow-up data and risk factors for
      congenital hearing loss. RESULTS: Confirmed hearing loss occurred in 8
      nonneonatal intensive care unit infants, a rate of 2.5/1000. Eighty percent of
      newborns who failed the initial hearing screen passed on rescreening before
      hospital discharge. This produced a false-positive rate of 0.8% and a
      corresponding positive predictive value of 24%. If inhospital rescreening had not
      occurred, our false-positive rate and positive predictive value would have been
      3.9% and 6.1%, respectively. CONCLUSIONS: Our simple intervention of rescreening
      all infants who failed their initial UNHS before hospital discharge reduced the
      false-positive rate of UNHS to 0.8%. We suggest that this simple, inexpensive
      intervention should be instituted for all similar UNHS programs.

PMID- 11230611
TI  - Head lice infestation: single drug versus combination therapy with one percent
      permethrin and trimethoprim/sulfamethoxazole.
AB  - BACKGROUND: Head lice infestation (HLI) is a vexing problem for pediatricians and
      families because lice are becoming resistant to approved antipediculosis agents.
      OBJECTIVE: This study compared the efficacy of 3 different treatments for HLI and
      determined whether combination therapy reduced treatment failures. DESIGN AND
      SETTING: A randomized, clinical trial performed in 3 private practices.
      PARTICIPANTS: The population was children ranging in age from 2 to 13 years.
      METHODS: HLI was diagnosed by direct inspection of the hair and scalp. Children
      were assigned to 1 of 3 groups: 1) 1% permethrin creme rinse (1% PER; n = 39); 2)
      oral administration of trimethoprim/sulfamethoxazole (TMP/SMX; n = 36); and 3) a
      combination of 1% PER and TMP/SMX (n = 40). Follow-up visits were done 2 and 4
      weeks later, and parents or caregivers of those who did not return were
      interviewed by telephone. If HLI was present at the 2-week follow-up, the child
      was retreated per their protocol. We defined successful treatment as the absence
      of adult lice and nymphal stage or eggs (nits). The presence of nits alone was
      not considered a treatment failure. RESULTS: At the 2-week follow-up visit,
      successful treatment for groups 1, 2, and 3 was 79.5%, 83%, and 95%,
      respectively. At the 4-week follow-up, successful treatment was 72%, 78%, and
      92.5% for groups 1, 2, and 3, respectively. The absolute risk reduction for
      recurrence comparing group 1 versus group 2 was 6%, group 2 versus group 3 was
      14%, and group 1 versus group 3 was 20%. No major adverse complications were seen
      in any treatment group. CONCLUSION: Our findings indicate that a combination of
      1% PER and TMP/SMX is an effective alternative therapy for HLI. We recommend that
      the dual therapy with 1% PER and oral TMP/SMX be used and reserved in cases of
      multiple treatment failures or suspected cases of lice-related resistance to
      therapy.

PMID- 11230612
TI  - Vaccination coverage and physician distribution in the United States, 1997.
AB  - BACKGROUND: How many physicians are needed in the United States and how they
      should be allocated geographically and among specialties has been the subject of
      intense debate, a debate that has often focused more on costs to third-party
      payers and government than on benefits to health. Child health is a central
      aspect of public health, and immunization is one of its most cost-effective and
      easily measured interventions. OBJECTIVE: To examine the association of
      immunization rates and delivery characteristics with the distribution of child
      health physicians in the United States in 1997. DESIGN: Cross-sectional
      ecological study, using the state as the unit of analysis, immunization rates and
      delivery characteristics (from the National Immunization Survey) as the main
      outcome measures, concentration of the principal physician specialties providing
      routine care to children (pediatric, family, and general physicians from the
      American Medical Association Masterfile) as the main risk factor, while
      controlling for demographic and economic factors (from the Bureau of the Census
      and other sources). RESULTS: Of the 96 689 physicians providing routine care to
      children, 37% were pediatric, 49% family, and 14% general physicians. Higher
      rates of vaccination, private sector vaccination, and increased numbers of public
      and private vaccination sites were all associated with the concentration of
      pediatricians but not of family or general physicians. The distribution of
      pediatricians was strongly associated with the distribution of residency
      positions. CONCLUSIONS: Pediatrician distribution is a strong correlate to
      immunization rates and delivery characteristics. Opportunities to affect
      pediatrician distribution may exist with allocation of residency positions.

PMID- 11230613
TI  - Racial and temporal variations in the prevalence of heart defects.
AB  - BACKGROUND: Documenting the prevalence and trends of congenital heart defects
      provides useful data for pediatric practice, health-care planning, and causal
      research. Yet, most population-based studies use data from the 1970s and 1980s.
      We sought to extend into more recent years the study of temporal and racial
      variations of heart defects occurrence in a well-defined population. METHODS: We
      used data from the Metropolitan Atlanta Congenital Defects Program, a population
      based registry with active case ascertainment from multiple sources. Heart
      defects were identified among liveborn infants up to 1 year old, among stillborn
      infants, and among pregnancy terminations to mothers residing in metropolitan
      Atlanta. RESULTS: From 1968 through 1997, the registry ascertained 5813 major
      congenital heart defects among 937 195 infants, for a prevalence of 6.2 per 1000.
      The prevalence increased to 9.0 per 1000 births in 1995 through 1997. The
      prevalence of ventricular septal defects, tetralogy of Fallot, atrioventricular
      septal defects, and pulmonary stenosis increased, whereas that of transposition
      of the great arteries decreased. For some defects, prevalence and trends varied
      by race. CONCLUSIONS: The prevalence of congenital heart defects is increasing.
      Whereas most findings likely result from improved case ascertainment and
      reporting, others might be because of changes in the distribution of risk factors
      in the population. The basis of the racial variations is incompletely understood.

PMID- 11230614
TI  - Incidence survey of Kawasaki disease in 1997 and 1998 in Japan.
AB  - OBJECTIVE: To describe the results of a nationwide epidemiologic survey of
      Kawasaki disease for the 2-year period 1997 and 1998. DESIGN: We sent a
      questionnaire to all hospitals with 100 beds or more throughout Japan (2663
      hospitals) requesting data on patients with Kawasaki disease. Study items
      included name, sex, date of birth, date of initial hospital visit, diagnosis,
      address, recurrence, sibling cases, gammaglobulin treatment, and cardiac lesion
      in the acute stage or 1 month after onset. RESULTS: Of the 2663 hospitals, 68.5%
      responded, reporting 12 966 patients-7489 males and 5477 females. Of the total
      patients reported, 6373 (incidence rate of 108.0 per 100 000 children <5 years
      old) occurred in 1997, and 6593 (111.7) in 1998. More than one half of the
      patients (54.9%) were <2 years old and 81.6% were <4 years old. In males, the
      incidence rates of cardiac lesions were 27.2 in the acute stage and 10.1 a month
      after onset. In females, the rates were 16.7 and 5.2, respectively. The incidence
      rates of cardiac lesions were highest in the youngest age group (<6 months old)
      both in the acute stage and 1 month after onset. The rates decreased with
      increasing ages. Although frequency of giant aneurysms was not high at the acute
      stage, it did not decrease 1 month after onset. CONCLUSION: The incidence rates
      have been steadily increasing for 11 years since 1987. The rate in 1998 was over
      1.5 times higher than that in 1987. The age and sex distributions were identical
      in each survey. Although most of the cardiac lesions at the acute stage decreased
      to half or less 1 month after onset, giant aneurysms did not decrease and existed
      persistently after 1 month.

PMID- 11230615
TI  - Racial divergence in adiposity during adolescence: The NHLBI Growth and Health
      Study.
AB  - BACKGROUND: Black women are particularly vulnerable to obesity, with a prevalence
      rate of >50%. The higher mortality and morbidity from cardiovascular disease,
      stroke, and diabetes have been attributed, in part, to their obesity. In recent
      years, a particular public health concern is the increasing secular trend in
      obesity with an even greater racial disparity, especially in girls and women.
      Between the early 1960s and late 1980s, the prevalence of obesity tripled in
      young black girls 6 to 11 years of age, while it doubled in white girls.
      Similarly, both overweight and obesity in adolescent girls 12 to 17 years of age
      also increased, with a greater increase again seen in adolescent black girls.
      This secular trend in obesity with a greater increase in black girls signals a
      potentially grave future chronic disease burden on black women, which is already
      higher than in white women. The increasing occurrence in children and adolescents
      of noninsulin-dependent diabetes, traditionally viewed as an adult-onset
      condition, may be a consequence of the currently high prevalence of obesity in
      American youth. Not surprisingly, this condition is seen more frequently among
      black youths. Prepubescent black girls are generally leaner than age-comparable
      white girls, but by 20 years of age, black women are considerably heavier than
      are white women. Thus, it is assumed that the racial disparity in adiposity
      evolves during adolescence. However, the specific age at which this occurs and
      underlying factors are yet to be identified because of the current paucity of
      longitudinal cohort data. OBJECTIVES: In 1985, the National Heart, Lung, and
      Blood Institute (NHLBI) initiated a 10-year longitudinal multicenter study (the
      NHLBI Growth and Health Study [NGHS]) to investigate the development of obesity
      in black and white girls during adolescence and its environmental, psychosocial,
      and cardiovascular disease risk factor correlates. The purpose of this report is
      to examine the natural history of adiposity and weight accretion during
      adolescence in a biracial cohort of girls to investigate the evolution of the
      racial divergence in adiposity and to examine the relationships between increases
      in adiposity and pubertal maturation, energy intake, and physical activity.
      PARTICIPANTS AND SETTING: A total of 2379 black (51%) and white (49%) girls, 9 to
      10 years of age, were recruited from public and parochial schools in Richmond,
      California, and Cincinnati, Ohio, and from families enrolled in a large health
      maintenance organization in the Washington, DC area. Participant eligibility was
      limited to girls and their parents who declared themselves as being either black
      or white and who lived in racially concordant households. DESIGN AND STATISTICAL
      ANALYSIS: The NGHS is a multicenter prospective study of black and white girls
      with annual visits from 9 to 10 years of age through 18 to 19 years of age. The
      follow-up rate was 89% at the 10th annual visit. Skinfold measurements were
      obtained at the triceps, suprailiac, and subscapular sites with Holtain calipers.
      Sexual maturation was assessed by trained registered nurses. The onset of
      menarche was ascertained annually by questionnaire. All clinical assessments were
      conducted using a common protocol by centrally trained staff. Longitudinal
      regression (generalized estimating equations) models were used to examine the
      relationship between adiposity and race, age, pubertal maturation, daily energy
      intake, and physical activity. MAIN OUTCOME MEASURES: The main outcome measure
      was the sum of skinfolds (SSF) at the triceps, subscapular, and suprailiac sites
      as an index of adiposity for comparison between the 2 racial groups. Body mass
      index (BMI; weight in kilograms divided by height in meters, squared)
      distributions were examined by age and race. RESULTS: Racial differences in SSF,
      unadjusted for maturation, were evident at 10 years of age. For each
      chronological age, there was a higher proportion of black girls with more
      advanced pubertal maturation than white girls. The 15th percentiles for SSF were
      similar and remained thus throughout the study. The median for SSF for black
      girls, although similar to the median SSF of white girls at 9 years of age,
      became greater for black girls at 12 years of age (36 mm vs 32.5 mm) and at age
      19 years the difference was 6 mm (49.5 mm vs 43.5 mm). In contrast, the
      difference in the 85th as well as the 95th percentile values for SSF were
      substantially higher in black girls at all ages (9 mm and 10 mm, or 18% and 15%,
      respectively, at age 9 years) and these racial differences widened with age (20
      mm and 26 mm, or 25% and 24%, respectively, by age 19 years). The racial
      difference in the median BMI increased from 0.4 to 2.3 kg/m(2) between ages 9 and
      19 years. Unlike SSF at the 15th percentile, the BMI for lean 9-year-old black
      girls was ~3% higher than whites. (ABSTRACT TRUNCATED)

PMID- 11230616
TI  - Psychological adjustment of adolescent girls with chronic fatigue syndrome.
AB  - OBJECTIVE: To examine psychosocial problems and adaptation of adolescent girls
      with chronic fatigue syndrome (CFS). METHODOLOGY: Thirty-six adolescent girls
      with CFS (mean age: 15.2 years; mean syndrome duration: 19.7 months) who
      fulfilled the criteria of the Centers for Disease Control and Prevention were
      examined by interviews regarding premorbid problems and by questionnaires
      regarding psychosocial functioning and distress, psychological attitudes, and
      coping resources. Data were compared with normative data. RESULTS: Of the
      adolescents, 86.1% reported 1 or more premorbid problems (58.3% physical, 38.9%
      psychological, and 52.8% familial). Normal adjustment was reported for
      psychosocial self-esteem, social abilities, and attentional abilities. High
      adjustment to adult social standards of behavior was found, but low perceived
      competence in specific adolescent domains, such as athletic ability, romance, and
      participation in recreational activities. The girls reported predominantly
      internalizing problems. Normal achievement motivation, no debilitating fear of
      failure, and high internal locus of control were observed. Palliative reaction
      patterns and optimism were predominantly used as coping strategies. CONCLUSIONS:
      The large number of premorbid problems suggests a possible contributing factor to
      the onset of the syndrome, although there were no reference data of healthy
      adolescents. In distinct domains of psychosocial adjustment, the adolescent girls
      with CFS showed strengths such as adequate self-esteem and scholastic and social
      abilities, and weaknesses such as low competence in adolescent-specific tasks and
      internalizing distress, which may partly be explained by syndrome-specific
      somatic complaints. The use of optimistic and palliative reaction patterns as
      coping strategies in this patient group indicates that the patients with CFS seem
      to retain an active and positive outlook on life, which may result in a rather
      adequate psychological adaptation to the syndrome, but also in maintenance of the
      syndrome by exceeding the physical limits brought about by the CFS. Our results
      on adjustment and coping strategies may be helpful to implement (individual)
      rehabilitation programs.

PMID- 11230617
TI  - Delayed hypersensitivity to tuberculin, total immunoglobulin E, specific
      sensitization, and atopic manifestation in longitudinally followed early Bacille
      Calmette-Guerin-vaccinated and nonvaccinated children.
AB  - BACKGROUND: Bacille Calmette-Guerin (BCG) is a strong T helper 1 incentive and,
      thus, may contribute to a decreased risk of T helper 2-dependent atopic disease.
      OBJECTIVE: To investigate the natural course of specific immunoglobulin E (IgE)
      responses and atopic disease in BCG-vaccinated and nonvaccinated children.
      PARTICIPANTS: Seven hundred seventy-four children from a prospectively followed
      birth cohort. OUTCOME MEASURES: Physical examination and case history were
      performed at 3, 6, 12, 18, 24, 36, 48, 60, 72, and 84 months of age. Total and
      specific serum IgE levels to 9 common inhalant and food allergens were determined
      (CAP; Pharmacia, Freiburg, Germany) at 12, 24, 36, 60, 72, and 84 months of age.
      Purified protein derivative (PPD) skin testing was performed at 84 months.
      RESULTS: Period and lifetime prevalences of atopic dermatitis and recurrent
      wheezing tended to be lower in the BCG-vaccinated group early in life, whereas no
      such trend was found after the second birthday or for allergic rhinitis. The
      proportion of children remaining free of clinical manifestations tended to be
      higher in the BCG-vaccinated group but differences decreased over time. No
      statistically significant differences were found for total IgE levels (median).
      Atopic sensitization tended to be lower among BCG-vaccinated children during the
      first 2 years of life. The diameter of the skin reaction to PPD did not correlate
      with total serum IgE. Clinical and serologic correlates of atopy were not
      significantly different between children with a skin test diameter of >/=5 mm and
      those with a smaller diameter. CONCLUSION: These results do not support the
      hypothesis that BCG vaccination in early infancy is associated with a
      subsequently markedly decreased risk of atopic sensitization or allergy. In
      addition, PPD skin test reactivity was not impaired in atopic individuals.

PMID- 11230618
TI  - Incidence and remission of asthma in schoolchildren: report from the obstructive
      lung disease in northern Sweden studies.
AB  - OBJECTIVE: An increasing prevalence of asthma has been reported worldwide as well
      as in Sweden. In 1996, the prevalence of asthma and type 1 allergy was
      investigated in a cohort of 3525 children 7 and 8 years old in 3 areas of
      northern Sweden. The aim of the present study was to estimate the incidence of
      asthma and to identify risk factors for incident cases over 1 year. METHODS: The
      study started with a parental questionnaire, the International Study of Asthma
      and Allergies in Childhood questionnaire with additional questions, a skin prick
      test, and a validation study. The cohort was followed up after 1 year with the
      same questions. The response rate to the questionnaire was 97% in 1996, and 3339
      children (97%) participated both in 1996 and 1997. RESULTS: The incidence of
      physician-diagnosed asthma was 0.9/100/year; of wheezing, 3.8/100/year; and of
      new frequent or daily users of asthma medicines, 1.1/100/year. There was no
      difference by sex. The risk factor pattern based on incident cases of asthma was
      different from that based on prevalent cases. Significant risk factors for
      incident asthma were a positive skin test (odds ratio [OR]: 9.3; 95% confidence
      interval [CI]: 3.8-22.7); low birth weight (OR: 7.4; 95% CI: 2.2-24.5); and
      family history of asthma (OR: 2.6; 95% CI: 1.1-6.3). Having or having had pets at
      home was associated with a decreased risk for asthma and wheezing based on
      prevalent cases, although it was associated with an increased risk for incidence
      of wheezing (OR: 2.9; 95% CI: 1.3-6.2). Remission of asthma, which was reported
      by 10% of the children with current asthma during 1 year, was associated with a
      negative skin test. CONCLUSION: The incidence of asthma at the age of 8 years was
      high, but remission was also common. Important risk factors for the development
      of asthma at this age were type 1 allergy, low birth weight, and family history
      of asthma. Furthermore, the results suggest that in a region where sensitivity to
      domestic animals is a strong risk factor for asthma, the presence of pets in the
      home may have different effects in early childhood compared with later in
      childhood.

PMID- 11230619
TI  - Solids and formula: association with pattern and duration of breastfeeding.
AB  - OBJECTIVES: To study changes in pattern and duration of breastfeeding associated
      with the introduction of solids and formula. STUDY DESIGN: Descriptive
      longitudinal, prospective study. SETTING: The participants were recruited from
      the maternity ward in the University Hospital in Uppsala, Sweden, between May
      1989 and December 1992. A total of 15 189 infants were born during the period, 1
      177 mother-infant pairs were found eligible for participation; 57% declined
      because of the perceived high workload. Study Population. Five hundred six mother
      infant pairs. METHODS: Daily recordings by the mothers on infant feeding, from
      the first week after delivery to the second menstruation postpartum or a new
      pregnancy; fortnightly home visits with structured interviews by a research
      assistant. RESULTS: Introduction of solids was associated with no or minor
      changes in breastfeeding frequency and suckling duration. Breastfeeding frequency
      remained constant the first month after the introduction and then declined
      slowly, while daily suckling duration started to decline slowly when solids were
      introduced. Breastfeeding duration was not associated with infants' age at
      introduction of solids. In infants given formula, as soon as regular formula
      feeds started, the breastfeeding frequency and suckling duration declined
      swiftly. The younger an infant was at the start of regular formula feeds, the
      shorter the breastfeeding duration. CONCLUSIONS: Health care personnel and
      parents need to be aware that introduction of solids and introduction of formula
      can have very different consequences for breastfeeding. If the aim is to
      introduce other foods to breastfed infants under the protection of breast milk,
      it is important to realize that formula is also another food and needs to be
      treated as such.

PMID- 11230620
TI  - Levels of interleukin-2, interferon-gamma, and interleukin-4 in bronchoalveolar
      lavage fluid from patients with Mycoplasma pneumonia: implication of tendency
      toward increased immunoglobulin E production.
AB  - OBJECTIVE: In connection with the possible relationship between Mycoplasma
      infection and the onset of asthma, several studies have shown not only a high
      level of serum total immunoglobulin E (IgE) but also the production of IgE
      specific to Mycoplasma or common allergens during the course of Mycoplasma
      infection. It has been suggested that the balance of T helper type 1 (TH1)/T
      helper type 2 (TH2) immune response may regulate the synthesis of IgE. The
      objective of this study was to investigate the pattern of cytokine response (TH1
      or TH2) during an episode of acute lower respiratory tract infection caused by
      Mycoplasma pneumoniae. STUDY DESIGN: Using a bronchoalveolar lavage (BAL) with
      flexible bronchoscopy procedure, this study determined the levels of interleukin
      (IL)-2, interferon (IFN)-gamma (TH1), and IL-4 (TH2) in the supernatant of BAL
      fluid as well as the BAL cellular profiles of patients with Mycoplasma pneumonia
      (n = 14). These results were compared with those of patients with pneumococcal
      pneumonia (n = 12) or those of children with no identifiable airway infections
      (control group: n = 8). RESULTS: The BAL cellular profile in the Mycoplasma
      pneumonia group was characterized by a high percentage of neutrophils and
      lymphocytes. A significantly increased level of IL-2 was found in both pneumonia
      groups, compared with the control group. In contrast, the IFN-gamma level was not
      different for the 3 groups. The level of IL-4 and ratio of IL-4/IFN-gamma were
      significantly elevated in the Mycoplasma pneumonia group, but not in the
      pneumococcal pneumonia group, compared with the controls. CONCLUSIONS: IL-4
      levels and IL-4/IFN-gamma ratios in BAL fluid are significantly higher in
      patients with Mycoplasma pneumonia than in patients with pneumococcal pneumonia
      or control participants. The BAL cytokine data suggest a predominant TH2-like
      cytokine response in Mycoplasma pneumonia, thus representing a favorable
      condition for IgE production.

PMID- 11230621
TI  - Incidence of congenital rubella syndrome at a hospital serving a predominantly
      Hispanic population, El Paso, Texas.
AB  - OBJECTIVE: The current epidemiology of rubella reveals an increase in the number
      of cases among adult Hispanics and an increase in the number of congenital
      rubella syndrome (CRS) cases among infants of Hispanic mothers. Recent rubella
      outbreaks have occurred primarily among adult Hispanics, many of whom are foreign
      born natives of countries where rubella vaccination is not routine or has only
      recently been implemented. The objective of this study was to estimate the
      incidence of CRS in a hospital serving a predominantly Hispanic population.
      METHODS: Hospital charts of infants <1 year old discharged between January 1,
      1994 and December 31, 1996 with International Classification of Diseases, Ninth
      Revision (ICD-9) discharge codes consistent with CRS were reviewed; we looked for
      cataracts, deafness, congenital heart defects, dermal erythropoiesis,
      microcephaly, meningoencephalitis, and other defects associated with CRS. We
      abstracted data on maternal and infant ethnicity, maternal age, gestational age,
      infants' birth weight, infants' clinical characteristics, and laboratory
      evaluation. Cases were categorized according to the Council of State and
      Territorial Epidemiologists' case classification for CRS. RESULTS: Of the 182
      infants with 1 or more ICD-9 codes consistent with CRS, 6 (3.3%) met either the
      confirmed or probable case definition for CRS. Two infants met the definition for
      confirmed CRS. Although laboratory tests for rubella immunoglobulin M antibodies
      were positive for both of these infants, only 1 of the cases had been reported to
      the state health department. Four other infants had clinical presentations that
      met the definition for a probable case. One of these had been tested for rubella
      immunoglobulin M antibodies, and the test was negative. The other 3 had not been
      tested. The rate of infants meeting the definition of confirmed and probable CRS
      was 3.1 per 10 000 hospital births. All confirmed and probable cases were among
      infants born to Hispanic mothers. Maternal country of origin was Mexico for the 2
      confirmed cases and 1 of the probable cases, and unknown for the remaining 3
      probable cases. CONCLUSION: The rate of confirmed and probable CRS among infants
      in this predominantly Hispanic population is higher than the reported rate in the
      United States in the vaccine era, which has been reported to range from
      approximately 0.01-0.08 per 10 000 live births. These findings indicate a need
      for heightened awareness of CRS among physicians who serve populations at risk
      for rubella. Physicians should report all confirmed and probable CRS cases to the
      state health department. The lack of appropriate laboratory testing in 3 infants
      with probable CRS indicates that physicians should consider a diagnosis of CRS in
      infants with some signs consistent with CRS, particularly in areas serving high
      numbers of individuals at risk for rubella.

PMID- 11230622
TI  - Is breastfeeding really favoring early neonatal jaundice?
AB  - OBJECTIVE: The purpose of this study was to evaluate the development of
      significant hyperbilirubinemia in a large unselected newborn population in a
      metropolitan area with particular attention to the relationship between type of
      feeding and incidence of neonatal jaundice in the first week of life. STUDY
      DESIGN: A population of 2174 infants with gestational age >/=37 weeks was
      prospectively investigated during the first days of life. Total serum bilirubin
      determinations were performed on infants with jaundice. The following variables
      were studied: type of feeding, method of delivery, weight loss after birth in
      relationship to the type of feeding, and maternal and neonatal risk factors for
      jaundice. Statistical analyses were performed using the z test for parametric
      variables and the t test for nonparametric variables. In addition, the multiple
      logistic regression allows for the estimation of the role of the individual
      characteristics in the development of hyperbilirubinemia. Data concerning serum
      bilirubin peak distribution in jaundiced newborns were analyzed using a single
      and a double Gaussian best fit at least squares. The t test was performed to
      compare 2 values (high and low) of the serum bilirubin peak in breastfed and
      supplementary-fed infants with those in bottle-fed infants. RESULTS: The maximal
      serum bilirubin concentration exceeded 12.9 mg/dL (221 micromol/L) in 112 infants
      (5.1%). The study demonstrated a statistically significant positive correlation
      between patients with a total serum bilirubin concentration >12.9 mg/dL (221
      micromol/L) and supplementary feeding; oppositely, breastfed neonates did not
      present a higher frequency of significant hyperbilirubinemia in the first days of
      life. However, best Gaussian fitting of our data suggests that a small
      subpopulation of breastfed infants have a higher serum bilirubin peak than do
      bottle-fed infants. Newborns with significant hyperbilirubinemia underwent a
      greater weight loss after birth compared with the overall studied population, and
      infants given mixed feeding lost more weight than breastfed and formula-fed
      newborns, indicating that formula has been administered in neonates who had a
      weight loss beyond a predetermined percentage of birth weight. Significant
      hyperbilirubinemia was also strongly associated with delivery by vacuum
      extractor, some perinatal complications (cephalohematoma, positive Coombs' test,
      and blood group systems of A, AB, B, and O [ABO] incompatibility) and Asian
      origin. Multiple logistic regression analysis shows that supplementary feeding,
      weight loss percentage, ABO incompatibility, and vacuum extraction significantly
      increase the risk of jaundice, while only cesarean section decreases the risk.
      CONCLUSION: The present study confirms the important role of fasting in the
      pathogenesis of neonatal hyperbilirubinemia, although breastfeeding per se does
      not seem related to the increased frequency of neonatal jaundice but to the
      higher bilirubin level in a very small subpopulation of infants with jaundice. In
      fact, in the breastfed infants, there is a small subpopulation with higher serum
      bilirubin levels. These infants, when starved and/or dehydrated, could probably
      be at high risk of bilirubin encephalopathy.

PMID- 11230623
TI  - Subcutaneous granuloma annulare in childhood: clinicopathologic features in 34
      cases.
AB  - OBJECTIVE: To gather clinicopathologic data on subcutaneous granuloma annulare
      (SGA), a subtype of granuloma annulare that occurs exclusively in children and is
      histologically similar to rheumatoid nodules. DESIGN: Retrospective record
      review. PATIENTS: Children <10 years old in whom SGA, deep granuloma annulare, or
      necrobiotic granuloma was diagnosed at the Mayo Clinic (Rochester, MN) from 1983
      to 1998. RESULTS: Thirty-four patients (21 girls and 13 boys; average age at
      diagnosis: 4.6 years) were found to have SGA. The lesions predominantly occurred
      in the lower extremity, especially in a pretibial location. Local recurrence
      within 1 month to 7 years was documented in 38.2%; recurrence at other locations
      was documented in 14.7%. Average follow-up was 60 months; during follow-up, no
      patients developed signs or symptoms of rheumatologic disease. Insulin-dependent
      diabetes mellitus was diagnosed in 2 patients, 1 before the development of SGA
      and 1 after it by 1 month. CONCLUSIONS: SGA is a lesion that presents as
      subcutaneous nodules on the lower extremities, hands, or scalp in young children.
      Recurrence is common but usually does not warrant additional biopsy.

PMID- 11230624
TI  - Prevalence and assessment of attention-deficit/hyperactivity disorder in primary
      care settings.
AB  - Research literature relating to the prevalence of attention-deficit/hyperactivity
      disorder (ADHD) and co-occurring conditions in children from primary care
      settings and the general population is reviewed as the basis of the American
      Academy of Pediatrics clinical practice guideline for the assessment and
      diagnosis of ADHD. Epidemiologic studies revealed prevalence rates generally
      ranging from 4% to 12% in the general population of 6 to 12 year olds. Similar or
      slightly lower rates of ADHD were revealed in pediatric primary care settings.
      Other behavioral, emotional, and learning problems significantly co-occurred with
      ADHD. Also reviewed were rating scales and medical tests that could be employed
      in evaluating ADHD. The utility of using both parent- and teacher-completed
      rating scales that specifically assess symptoms of ADHD in the diagnostic process
      was supported. Recommendations were made regarding the assessment of children
      with suspected ADHD in the pediatric primary care setting.

PMID- 11230625
TI  - The use of public education in practice.

PMID- 11230626
TI  - Cafe au lait spots: the pediatrician's perspective.

PMID- 11230628
TI  - Index of suspicion. Case 1. Diagnosis: Rat-bite fever.

PMID- 11230627
TI  - Consultation with the specialist: cardiac dysrhythmias.

PMID- 11230629
TI  - Visual diagnosis: a child who has a nosebleed and high blood pressure.

PMID- 11230630
TI  - Off the beaten path: transbrachial approach for native fistula interventions.

PMID- 11230631
TI  - Of posters and exhibits and other things.

PMID- 11230632
TI  - Pelvic floor imaging.
AB  - A greater awareness of the therapies now available for pelvic floor dysfunction
      has increased demand for specialized imaging of this region. Some of the
      techniques required are available at relatively few centers, and the purpose of
      this review is to introduce the emerging subspecialty of pelvic floor imaging to
      a more general readership. Pelvic floor anatomy is complex and is being unraveled
      by means of magnetic resonance (MR) imaging. This is discussed in detail by using
      a global, rather than a compartmentalized, anatomic approach. The physiology of
      normal urinary and anal function and the routine clinical tests applied to them
      are outlined. The imaging techniques involved include MR imaging, endosonography,
      and fluoroscopy. The main investigations include video urodynamic imaging,
      evacuation proctography, dynamic cystoproctography, dynamic MR imaging of the
      pelvic floor, and endoluminal imaging of the anal sphincters with MR imaging and
      ultrasonography. These are described in detail, and their role with regard to the
      main pathologic conditions of the pelvic floor--urinary and anal incontinence,
      constipation, and prolapse--are discussed.

PMID- 11230633
TI  - Adrenal masses: quantification of fat content with double-echo chemical shift in
      phase and opposed-phase FLASH MR images for differentiation of adrenal adenomas.
AB  - PURPOSE: To quantify fat content in adrenal lesions with double-echo chemical
      shift magnetic resonance (MR) imaging in a phantom study and to differentiate
      adrenal adenomas from other adrenal masses by assessing fat content in a clinical
      study. MATERIALS AND METHODS: The study consisted of two parts: a phantom study
      and a clinical study. To explore the effect of the T1 value on in- and opposed
      phase MR images of fat-containing tissues, phantom models with various
      proportions of fat and gadopentetate dimeglumine concentrations were implemented.
      Signal intensity (SI) indexes ([SI in-phase - SI opposed-phase]/SI in-phase) were
      calculated with double-echo fast low-angle shot (FLASH) MR imaging. In the
      clinical study, 23 patients with 28 adrenal masses (16 adrenal adenomas, nine
      adrenal metastases, and three pheochromocytomas) underwent double-echo FLASH MR
      imaging, and SI indexes were calculated. RESULTS: SI index reached a maximum of
      0.87 at 53% fat fraction for gadopentetate dimeglumine concentration at 0.5
      mmol/L as the simulated T1 of the adrenal mass. The SI indexes of the adrenal
      adenomas, adrenal metastases, and pheochromocytomas, respectively, were 0.36, 
      0.15, and -0.07, and estimated fat fraction from the phantom study was 26.5%, 0%,
      and 0%. All adrenal adenomas contained fat on double-echo FLASH images. There was
      no overlap in SI index between adenomas and other tumors. CONCLUSION: Preliminary
      experience indicates that quantitative measurement of the fat fraction of adrenal
      masses is possible with the double-echo chemical shift FLASH technique and allows
      for differentiating adrenal adenomas from other adrenal masses.

PMID- 11230634
TI  - Emphysematous pyelitis: findings in five patients.
AB  - Emphysematous pyelitis (EP) is a benign entity. To our knowledge, it has not been
      reported frequently in the radiology literature. Previous articles have not
      focused on EP but rather have included other gas-forming entities (eg,
      emphysematous pyelonephritis [EPN]). The authors describe imaging findings in EP
      and distinguish them from findings in EPN in five cases. Computed tomography is
      the current method for demonstrating isolated gas production inside the urinary
      collecting system. The prognosis is excellent, with rapid complete recovery after
      medical treatment.

PMID- 11230635
TI  - Renal tolerance of a neutral gadolinium chelate (gadobutrol) in patients with
      chronic renal failure: results of a randomized study.
AB  - PURPOSE: To assess the renal tolerance of 1.0 mol/L gadobutrol as an electrically
      neutral contrast agent at magnetic resonance (MR) imaging in patients with
      impaired renal function. MATERIALS AND METHODS: Twenty-one patients with impaired
      renal function were enrolled in this prospective randomized study and classified
      into two subgroups according to their creatinine clearance: group 1 (n = 12),
      less than 80 mL/min (<1.33 mL/sec) and greater than 30 mL/min (>0.50 mL/sec);
      group 2 (n = 9), less than 30 mL/min (<0.50 mL/sec) and not requiring dialysis.
      Gadobutrol (1.0 mol/L) was injected intravenously at randomly assigned doses of
      either 0.1 or 0.3 mmol per kilogram of body weight. Changes in vital signs,
      clinical chemistry, and urinalysis results, including creatinine clearance, were
      monitored before, at 6 hours, and then every 24 hours until 72 hours (group 1) or
      120 hours (group 2) after intravenous injection of gadobutrol. Hematologic
      results were checked every other day. RESULTS: No serious adverse event occurred,
      and no clinically relevant changes in vital signs, hematologic results, clinical
      chemistry, or urinalysis results were detected in the observation period. Markers
      for glomerular filtration (creatinine, cystatin C, beta2-microglobulin,
      creatinine clearance) and tubular function (N-acetyl-beta-D-glucosaminidase,
      alpha1-microglobulin) were unaffected by gadobutrol in both groups. CONCLUSION:
      Gadobutrol did not affect renal function and, therefore, proved to be a safe MR
      contrast agent in patients with impaired renal function. Even in patients with
      marginal excretory function (creatinine clearance, <30 mL/min [<0.50 mL/sec]),
      prehydration or treatment with diuretics or hemodialysis are not required after
      the administration of gadobutrol.

PMID- 11230636
TI  - Helical CT evaluation of the perirenal space and its boundaries: a cadaveric
      study.
AB  - PURPOSE: To determine whether the perirenal spaces communicate across the midline
      and with the pelvic extraperitoneal spaces. MATERIALS AND METHODS: Helical CT was
      used to guide the sequential injection of 100-mL intravenous boluses of dilute
      contrast medium, up to 300 mL, into the perirenal space of eight embalmed
      cadavers (three male, five female; mean age at death, 82 years; range, 72-93
      years), with four left-sided and four right-sided injections. All images were
      acquired after the final injection (300 mL total) to facilitate coronal and
      sagittal reconstruction of relevant images. All images were reviewed to assess
      the flow pathways of contrast medium from the perirenal space to other
      retroperitoneal spaces. RESULTS: In three cadavers that received left perirenal
      space injections and in two cadavers that received right perirenal space
      injections, communication was seen with the contralateral perirenal space through
      an area anterior to the aorta and inferior vena cava. In three cadavers that
      received right perirenal space injections, contrast material flowed from the
      right perirenal space to outline the bare area of the liver. Communication
      between the perirenal and pelvic extraperitoneal spaces was seen in all eight
      cadavers; contrast material extended into the pelvic extraperitoneal and
      presacral spaces. CONCLUSION: These findings show that the perirenal spaces
      communicate with each other across the midline and with the pelvic
      extraperitoneal spaces. Clinical implications are that perinephric collections
      can potentially flow into the pelvis or across the midline.

PMID- 11230637
TI  - Interstitial MR lymphography with a conventional extracellular gadolinium-based
      agent: assessment in rabbits.
AB  - PURPOSE: To evaluate gadoterate meglumine as a contrast agent for interstitial
      magnetic resonance (MR) lymphography in combination with an adapted fast three
      dimensional (3D) MR sequence. MATERIALS AND METHODS: In 12 New Zealand White
      rabbits, 0.5 mL of undiluted gadoterate meglumine was injected subcutaneously
      into the dorsal foot pad (n = 9) or the foreleg (n = 3) bilaterally. Immediately
      after administration, a slight massage was performed at the injection site.
      Imaging was performed with a 3D spoiled gradient-recalled echo sequence (6.7/1.6
      [repetition time msec/echo time msec]; field of view, 28.0 x 19.6; two signals
      acquired) similar to that used for 3D MR angiography. Thus, 3D maximum intensity
      projection images could be obtained. Images were obtained before injection and 5,
      15, 30, 60, and 120 minutes after injection. RESULTS: In the hind legs, as many
      as four successive lymph node groups were depicted with maximum enhancement after
      5-15 minutes for the popliteal lymph node group, 15-30 minutes for the inguinal
      lymph group, and 30-60 minutes for the iliac-paraaortal lymph node group; the
      iliac-paraaortal lymph node group was not consistently enhanced. In the forelegs,
      four successive lymph node groups, including axillary and mediastinal lymph node
      groups, showed marked gadolinium uptake, with maximum enhancement 5-15 minutes
      after injection. CONCLUSION: As a widely tested positive-enhancing T1 contrast
      agent with favorable safety features, gadoterate meglumine allows the depiction
      of three to four successive lymph node groups early after subcutaneous injection.
      With the sequence used, 3D MR lymphangiograms can be obtained.

PMID- 11230638
TI  - Contrast-enhanced MR imaging of coronary arteries: comparison of intra- and
      extravascular contrast agents in swine.
AB  - PURPOSE: To compare the efficacy of an intravascular contrast agent, gadomer-17,
      in improving magnetic resonance (MR) imaging of coronary arteries with that of an
      extravascular agent, gadopentetate dimeglumine, in pigs. MATERIALS AND METHODS:
      Eight pigs underwent imaging after three injections: 0.20 mmol of gadopentetate
      dimeglumine per kilogram of body weight and 0.05 and 0.10 mmol/kg gadomer-17.
      Coronary images were acquired repeatedly after each injection by using an
      inversion-recovery-prepared segmented three-dimensional sequence with either
      breath holding (n = 4) or respiratory gating (n = 4). Coronary artery-to
      myocardium contrast-to-noise ratios (CNRs) were compared between injections.
      RESULTS: At breath-hold imaging, substantial CNR improvement over precontrast
      images was observed in images acquired during the first pass of gadopentetate
      dimeglumine in coronary arteries and up to 6 and 10 minutes after 0.05 and 0.10
      mmol/kg of gadomer-17 injections, respectively. The CNR with 0.10 mmol/kg of
      gadomer-17 was 20% (P <.05) higher than that with gadopentetate dimeglumine at
      first-pass imaging. At respiratory-gated imaging, significant CNR improvement (P
      <.05) over precontrast images was observed in images acquired up to 10, 30, and
      50 minutes after gadopentetate dimeglumine and both gadomer-17 injections,
      respectively. The CNR on the first images obtained after 0.10 mmol/kg gadomer-17
      injection was 168% (P <.05) higher than that on the images obtained after
      gadopentetate dimeglumine injection. CONCLUSION: Gadomer-17 provided greater and
      more persistent CNR improvements than did gadopentetate dimeglumine; further
      evaluation of its utility for coronary imaging in humans is warranted.

PMID- 11230639
TI  - Digital chest radiography with a solid-state flat-panel x-ray detector: contrast
      detail evaluation with processed images printed on film hard copy.
AB  - PURPOSE: To evaluate and compare human observer performance in a contrast-detail
      test by using postprocessed hard-copy images from a digital chest radiography
      system and conventional screen-film radiographs. MATERIALS AND METHODS: The
      digital radiography system is based on a large-area flat-panel x-ray detector
      with a structured cesium iodide scintillator layer and an amorphous silicon thin
      film transistor array for image readout. Images of a contrast-detail phantom were
      acquired at two exposure levels by using two standard thoracic screen-film
      systems and the digital system at matched dose. By using images of the phantom
      processed with standard chest image postprocessing techniques, a four-alternative
      forced-choice observer perception study was performed, and the number of
      detectable test signals (disk-shaped objects 0.3-4.0 mm in diameter) was
      determined for each image type. RESULTS: On average, observers detected more test
      signals on digital images than on screen-film radiographs at all diameters up to
      2.0 mm and an equivalent number at larger diameters. Test signals with lower
      inherent subject contrast were detected more readily on digital images than on
      screen-film images, even when x-ray exposure levels for the digital system were
      reduced by 20%. CONCLUSION: Observer performance in a contrast-detail detection
      task can be improved by using images acquired with the flat-panel digital chest
      radiography system as compared with those acquired with state-of-the-art screen
      film combinations.

PMID- 11230640
TI  - Imaging characteristics of an amorphous silicon flat-panel detector for digital
      chest radiography.
AB  - PURPOSE: To evaluate the imaging characteristics of an amorphous silicon flat
      panel detector (FPD) for digital chest radiography. MATERIALS AND METHODS: The 41
      x 41-cm digital FPD is constructed on a single monolithic glass substrate with a
      structured cesium iodide scintillator layer and an amorphous silicon thin-film
      transistor array for image readout. Basic imaging characteristics of the FPD and
      associated image processing system were assessed on acquired images, including
      linearity, repeatability, uniformity of response, modulation transfer function
      (MTF), noise power spectrum, detective quantum efficiency (DQE), contrast
      sensitivity, and scatter content. Results with the FPD system were compared to
      those with a storage phosphor computed radiography (CR) system. RESULTS: Images
      obtained with the FPD demonstrated excellent uniformity, repeatability, and
      linearity, as well as MTF and DQE that were superior to those with the storage
      phosphor CR system. The contrast and scatter content of images acquired with the
      FPD were equivalent to those acquired with the storage phosphor system.
      CONCLUSION: The FPD provides radiographic images with excellent inherent physical
      image quality.

PMID- 11230641
TI  - Acute respiratory distress syndrome caused by pulmonary and extrapulmonary
      injury: a comparative CT study.
AB  - PURPOSE: To determine computed tomographic (CT) differences between acute
      respiratory distress syndrome (ARDS) due to pulmonary injury (ARDS(p)) and
      extrapulmonary injury (ARDS(ex)). MATERIALS AND METHODS: CT appearances in 41
      patients (27 male, 14 female; mean age, 47.1 years +/- 17.1 [SD]; age range, 17
      79 years; those with ARDS(p), n = 16; those with ARDS(ex), n = 25) were
      categorized as typical or atypical of ARDS by two observers. The extent of
      individual CT patterns was also quantified. RESULTS: Typical CT appearances were
      more frequent in ARDS(ex) than ARDS(p) (18 [72%] of 25 vs five [31%] of 16
      patients, respectively; P <.01). Sensitivity, specificity, and accuracy of a
      typical CT pattern for the diagnosis of ARDS(ex) were 72%, 69%, and 71%,
      respectively. Atypical appearances were characterized by more extensive
      nondependent intense parenchymal opacification (IPO) (P =.03) and cysts (P =.05),
      whereas typical CT appearances had more extensive dependent IPO (P =.01). Typical
      appearances at CT were independently related to the cause of ARDS (odds ratio,
      8.9; 95% CI: 1.8, 44.2; P <.01) but were independent of the time from intubation.
      Foci of nondependent IPO were more extensive in ARDS(p) (P =.05) than ARDS(ex),
      but this finding was ascribable to differences in time to CT (after intubation)
      between ARDS(p) and ARDS(ex). CONCLUSION: The differentiation between ARDS(p) and
      ARDS(ex) can, with some caveats, be based on whether the CT appearances are
      typical or atypical of ARDS but not on any individual CT pattern in isolation.

PMID- 11230642
TI  - Thin-section CT finding in 250 volunteers: assessment of the relationship of CT
      findings with smoking history and pulmonary function test results.
AB  - PURPOSE: To evaluate the frequency and morphologic characteristics of air
      trapping in volunteers with various smoking habits. MATERIALS AND METHODS: Two
      hundred fifty volunteers (133 women, 117 men; mean age, 39 years), including 144
      smokers, 47 ex-smokers, and 59 nonsmokers, prospectively underwent inspiratory
      and expiratory high-spatial-resolution computed tomography (CT) and pulmonary
      function tests (PFTs). The frequency and characteristics of air trapping were
      evaluated according to the population's smoking habits and PFT results. RESULTS:
      The overall frequency of air trapping was 62% (155 of 250 subjects). Lobular air
      trapping was depicted in 117 (47%) of 250 subjects, without significant
      differences among smokers (n = 91), ex-smokers (n = 33), and nonsmokers (n = 31)
      (P =.118). Segmental and lobar air trapping (38 [15%] of 250) were more frequent
      among smokers (24 [26%] of 91) and ex-smokers (nine [27%] of 33) (P <.001). No
      relationship was found between air trapping and functional indexes of small
      airway disease when the CT pattern of air trapping was considered. The strongest
      relationship between CT abnormalities and functional alterations at the small
      airways level was between inspiratory CT features of bronchiolitis: ground-glass
      opacity, ill-defined micronodules, bronchiolectasis, and air flow at low lung
      volumes. CONCLUSION: Whereas a significant relationship was observed between
      segmental and lobar air trapping and cigarette consumption, lobular air trapping
      was not found to reflect functional impairment at the small-airways level.

PMID- 11230643
TI  - Measurement of the gadopentetate dimeglumine partition coefficient in human
      myocardium in vivo: normal distribution and elevation in acute and chronic
      infarction.
AB  - PURPOSE: To establish a method for measuring the partition coefficient (lambda)
      of gadopentetate dimeglumine in humans in vivo, evaluate the spatial and
      intersubject variation in the lambda of normal myocardium, and compare these
      values on a regional basis with lambda values of acute and chronic infarcted
      myocardium. MATERIALS AND METHODS: Twelve healthy subjects and patients with
      acute (n = 5) or chronic (n = 5) myocardial infarction underwent magnetic
      resonance imaging at 1.5 T. Look-Locker images were acquired at four short-axis
      levels to measure myocardial and blood longitudinal relaxation time at baseline
      and after a 30-40-minute infusion of gadopentetate dimeglumine. lambda was
      calculated as DeltaR1(M)/DeltaR1(B, )where M = myocardium, and B = blood.
      RESULTS: The magnitude of the estimated lambda in normal myocardium was uniform
      over the entire myocardium at 0.56 mL/g +/- 0.10 (SD). The lambda values in
      patients with acute (0.91 mL/g +/- 0.11, P <.001) or chronic (lambda = 0.78 mL/g
      +/- 0.09, P <.001) infarction were significantly elevated, as compared with those
      in healthy subjects. A 20% elevation in lambda, as compared with the mean value
      of a corresponding normal circumferential segment, allowed identification of
      chronically (sensitivity, 88%; specificity, 96%) or acutely (sensitivity, 100%;
      specificity, 98%) infarcted segments. CONCLUSION: Quantification of the lambda in
      vivo allows differentiation between normal and acutely or chronically infarcted
      myocardium, with high sensitivity and specificity.

PMID- 11230644
TI  - Brachial arterial access: endovascular treatment of failing Brescia-Cimino
      hemodialysis fistulas--initial success and long-term results.
AB  - PURPOSE: To evaluate safety and efficacy of endovascular interventions in failing
      antebrachial Brescia-Cimino hemodialysis fistulas in consecutive patients.
      MATERIALS AND METHODS: Altogether, 103 interventions were performed in 53 Brescia
      Cimino shunts in 51 patients by means of antegrade brachial arterial access.
      Twelve interventions were initiated with pharmacomechanical thrombolysis and/or
      thromboaspiration. All interventions included balloon angioplasty that was
      completed with stent placement in eight cases and with endovascular brachytherapy
      with an iridium 192 source in five cases. RESULTS: The technical success rate of
      the primary interventions was 92% (49 of 53) and that for all interventions was
      95% (98 of 103). The rate of major complications was 4% (four of 103). Clinical
      success was achieved in 92% (95 of 103) of the interventions. By including the
      initial failures, 58% +/- 7 (standard error of the estimate), 44% +/- 8, 40% +/-
      8, and 32% +/- 10 primary and 90% +/- 5, 85% +/- 5, 79% +/- 7, and 79% +/- 7
      secondary clinical patency rates were registered at 6 months and 1, 2, and 3
      years, respectively, by means of Kaplan-Meier analysis. The location of the main
      treated lesion at the arteriovenous anastomosis (P =.03) was a predictor of
      poorer long-term patency. CONCLUSION: Endovascular interventions with antegrade
      brachial arterial access are highly effective in restoring function in failing
      Brescia-Cimino fistulas.

PMID- 11230645
TI  - Ulcerlike lesions of the aorta: imaging features and natural history.
AB  - PURPOSE: To document the natural history of ulcerlike aortic lesions and
      determine whether any computed tomographic (CT) features predict outcome.
      MATERIALS AND METHODS: CT scans from 1994 to 1998 that depicted an ulcerlike
      aortic lesion were retrospectively evaluated. Features evaluated included lesion
      and aortic size and intramural hematoma. Initial CT findings were correlated with
      clinical data and subsequent CT findings. RESULTS: There were 56 lesions in 38
      patients. Follow-up (mean, 18.4 months) CT scans were available for 33 lesions.
      Stability of the lesion and adjacent aorta was noted in 21 lesions. Two lesions
      were unchanged, although associated intramural hematoma regressed over 1-2
      months. Ten lesions showed mild to moderate increase in aortic diameter (mean
      follow-up, 19.8 months) either with (seven lesions) or without (one lesion)
      increase in size of the lesion or with incorporation of the lesion into the
      aortic wall contour (two lesions). Of all 56 lesions, 37 were clinically stable,
      two were associated with recurrent chest and/or back pain, eight underwent
      surgical resection or stent placement, and two were in patients who died. Seven
      lesions were in patients lost to follow-up. No initial CT feature was predictive
      of CT outcome, although lack of pleural effusion correlated with clinical
      stability. CONCLUSION: Most ulcerlike aortic lesions are asymptomatic and do not
      enlarge. About one-third of lesions progress, generally resulting in mild
      interval aortic enlargement.

PMID- 11230646
TI  - Intraarterial chemotherapy for brain tumors by using a spatial dose fractionation
      algorithm and pulsatile delivery.
AB  - PURPOSE: To evaluate the cause of complications in intraarterial chemotherapy for
      brain tumors and validate a dosage algorithm based on arterial territory.
      MATERIALS AND METHODS: Four hundred sixty-two procedures were performed in 113
      patients. Technique included pulsatile infusion of a chemotherapeutic agent.
      Dosage was calculated per hemisphere and divided per arterial territory according
      to a spatial dose fractionation algorithm based on the vascular territories of
      major cerebral arteries: middle cerebral artery, 60%; anterior cerebral artery,
      20%; posterior cerebral artery, 15%; and perforator arteries, 5%. Hospital charts
      of all patients were retrospectively reviewed for complications, with specific
      attention given to the angiograms to determine a cause. Then, subgroup analysis
      of the chemotherapy protocol with the largest patient population was performed to
      evaluate predictors of complications. RESULTS: Six (1.3%) complications were
      asymptomatic; 12 (2.6%), transient neurologic; three (0.6%), permanent minor
      neurologic; three (0.6%), permanent major neurologic; and 32 (7.0%), seizures. In
      the subgroup analysis, the hemispheric dose administered according to the
      algorithm was strongly predictive of seizure and neurologic deficit. CONCLUSION:
      Neurotoxicity of intraarterial cerebral chemotherapy can be minimized by using
      pulsatile injection and the described spatial dose fractionation algorithm.

PMID- 11230647
TI  - Initial angiographic appearance of intracranial vascular occlusions in acute
      stroke as a predictor of outcome of thrombolysis: initial experience.
AB  - PURPOSE: To determine whether the initial angiographic morphology and location of
      intracranial arterial occlusions in acute stroke are reliable predictors of
      success of thrombolysis. MATERIALS AND METHODS: Thirty-three intracranial
      occlusions were studied in 32 patients who underwent intraarterial thrombolysis
      with urokinase within 6 hours from clinical onset of stroke symptoms. The initial
      angiographic appearance of each occlusion was categorized as cutoff, tapered,
      meniscus, tram-track, or tandem. Following thrombolysis, outcomes were classified
      as complete, partial, or no recanalization. RESULTS: Complete recanalization was
      accomplished in 17 of the 33 lesions, partial recanalization in nine, and no
      effect in seven. Tram-track (n = 3) and tapered (n = 7) lesions demonstrated the
      highest rates of at least partial recanalization (100% and 86%, respectively),
      whereas cutoff lesions (n = 13) demonstrated the lowest rate (69%). Intracranial
      hemorrhage was associated with higher doses of urokinase. Complete recanalization
      success rates were 60% for M1 lesions (n = 10), 43% for M2 or A2 lesions (n =
      14), and 33% for M3 lesions (n = 3). Vertebrobasilar lesion (n = 5) success rates
      for complete and at least partial recanalization were 80% and 100%, respectively.
      CONCLUSION: Relationships were found to exist between the success rate of
      recanalization and initial angiographic lesion location and morphology, which
      represent important trends; however, further studies with a larger sample size
      are needed.

PMID- 11230649
TI  - The duodenal wind sock sign.

PMID- 11230648
TI  - Embolization as a first approach with endoscopically unmanageable acute
      nonvariceal gastrointestinal hemorrhage.
AB  - PURPOSE: To determine technical and clinical results of embolization of
      endoscopically unmanageable nonvariceal gastrointestinal hemorrhage (GIH).
      MATERIALS AND METHODS: Results of 40 embolizations in 91 patients who underwent
      arteriography for acute nonvariceal GIH were retrospectively studied. GIH was
      upper, lower, or transpapillar (hemobilia, pancreatic duct bleeding). Clinical
      parameters and embolization data were assessed for clinical success and in
      hospital survival. RESULTS: Technical success (bleeding target devascularization)
      was achieved in all patients except one with upper GIH (39 [98%] of 40 patients).
      No bowel complications occurred. One partial liver lobe and one partial spleen
      infarction were noted. Five (13%) of 39 patients bled again within 3 days; all
      had upper GIH (P =.049). Clinical success (no rebleeding after 30 days) was
      achieved in 32 (82%) of 39 patients. Clinical success occurred in 13 (68%) of 19
      patients with upper GIH, in 10 (91%) of 11 with lower GIH, and in all with
      transpapillar GIH (P =.084). Mortality rate was 28% (11 of 40 patients), equally
      spread over upper, lower, and transpapillar GIH (P =.87). Blood loss (hemoglobin
      level < 80 g/L, P =.041), use of packed cells (P =.049) and fresh frozen plasma
      (P =.006); shock (P =.047); and corticosteroid use (P =.036) were related to
      rebleeding. Shock (P =.039) and use of fresh frozen plasma (P =.003) before
      embolization and rebleeding (P =.012), coagulopathy (P =.007), and need for
      surgery (P =.03) after embolization were strongly correlated with mortality.
      CONCLUSION: Embolization is an effective first approach with lower and
      transpapillar GIH after endoscopy; it was less effective with upper GIH.

PMID- 11230650
TI  - Peripheral T-cell lymphoma of the colon: double-contrast barium enema examination
      findings in six patients.
AB  - PURPOSE: To evaluate radiologic findings of peripheral T-cell lymphoma (PTCL) of
      the colon at double-contrast barium enema examination. MATERIALS AND METHODS:
      Double-contrast barium enema findings in six patients with pathologically proved
      PTCL of the colon were retrospectively evaluated and compared with colonoscopic
      and histopathologic findings. RESULTS: There was a diffuse involvement of almost
      all segments of the colon in four patients and a focal segmental involvement in
      two. Frequent findings at double-contrast barium enema examination included
      geographic ulcerations (n = 6), aphthous ulcerations (n = 4), pseudopolyps (n =
      4), circumferential luminal narrowing (n = 4), and ileocecal deformity (n = 4).
      CONCLUSION: PTCL of the colon manifested as either a diffuse or a focal segmental
      lesion and showed extensive mucosal ulceration at double-contrast barium enema
      examination. These findings are similar to those of inflammatory bowel disease
      and are different from those of colorectal lymphoma with the B-cell phenotype.

PMID- 11230651
TI  - Outer diameter of the vermiform appendix as a sign of acute appendicitis:
      evaluation at US.
AB  - PURPOSE: To evaluate the usefulness and limitations of the outer diameter of the
      vermiform appendix at cross-sectional ultrasonography to confirm or rule out
      acute appendicitis. MATERIALS AND METHODS: In a prospective study, outer
      appendiceal diameters in 240 control subjects and in 278 patients suspected of
      having acute appendicitis who did (n = 98) or did not (n = 180) have acute
      appendicitis were measured. RESULTS: Outer appendiceal diameters in the control
      subjects ranged between 2 and 13 mm, and in 55 (23%) of 240 control subjects,
      diameters were 6 mm or more. Diameters in the symptomatic patients without acute
      appendicitis ranged between 2 and 11 mm, and 57 (32%) of 180 patients had
      diameters of 6 mm or more. Diameters of acutely inflamed appendices ranged
      between 6 and 30 mm. A diameter of 6 mm or more confirmed acute appendicitis with
      a sensitivity of 100%; a specificity of 68%; positive and negative predictive
      values of 63% and 100%, respectively; and an accuracy of 79%. CONCLUSION: The
      outer appendiceal diameter of 6 mm or more as a sign of acute appendicitis
      provides high sensitivity but limited specificity. This diagnostic criterion is
      more useful in excluding acute appendicitis than in confirming it.

PMID- 11230652
TI  - Hypervascular hepatocellular carcinoma: detection with double arterial phase
      multi-detector row helical CT.
AB  - PURPOSE: To assess whether double arterial phase imaging with multi-detector row
      helical computed tomography improves detection of hypervascular hepatocellular
      carcinoma (HCC). MATERIALS AND METHODS: Fifty-one patients with 96 hypervascular
      HCCs underwent double arterial phase imaging of the entire liver. At measured
      delay after intravenous administration of 2 mL/kg of contrast medium at a rate of
      5 mL/sec, the early and late arterial phase images were obtained serially during
      a single breath hold with interscan delay of 5.0 seconds. Detector row
      configuration of 2.5 x 4 mm, pitch of 6, and scanning time of 10.5 seconds for
      each phase were used. Forty 5-mm-thick reconstruction images were obtained for
      each phase. Each image set was interpreted separately by three observers, who
      were unaware of tumor burden in the liver, to detect hypervascular HCC.
      Sensitivity, positive predictive value, and area below the receiver operating
      characteristic curve (A(z)) for early and late arterial phases separately and
      together were calculated. RESULTS: Mean sensitivity and positive predictive value
      for hypervascular HCC were 54% and 85% for the early arterial phase, 78% and 83%
      for the late arterial phase, and 86% and 92% for the double arterial phase,
      respectively. Double arterial phase imaging showed significantly superior
      sensitivity compared with early or late arterial phase imaging alone for
      detecting HCC (P <.05). The mean A(z) value for double arterial phase was
      significantly higher than that for early or late arterial phase imaging alone (P
      <.05). Double arterial phase imaging showed the lowest number of false-positive
      lesions. CONCLUSION: Double arterial phase imaging is recommended to improve
      detection of hypervascular HCCs and reduce false-positive lesions.

PMID- 11230653
TI  - Abdominal thrombotic and ischemic manifestations of the antiphospholipid antibody
      syndrome: CT findings in 42 patients.
AB  - PURPOSE: To determine the abdominal computed tomographic (CT) findings in
      patients with antiphospholipid antibody syndrome (APS). MATERIALS AND METHODS:
      Retrospective review of medical records from two university medical centers from
      1994 through 1997 revealed 215 patients who had a hypercoagulable state
      attributed to primary or secondary APS. Abdominal CT findings in these patients
      were reviewed for evidence of large-vessel occlusion or visceral ischemia.
      RESULTS: In 42 (19.5%) of 215 patients with APS (age range, 32-65 years; mean
      age, 42 years), abdominal thromboses or ischemic events were detected at CT.
      Twenty-two (52%) had major vascular thromboses, including those in the inferior
      vena cava (n = 10), portal and superior mesenteric veins (n = 7), splenic vein (n
      = 4), and aorta (n = 1). Thirty-six (86%) patients had abdominal visceral
      ischemia resulting in renal infarction (n = 22), bowel ischemia (n = 13), splenic
      infarction (n = 6), pancreatitis (n = 3), hepatic infarction (n = 1), and/or
      hepatic dysfunction with portal hypertension (n = 1). In some patients, more than
      one abdominal organ and/or vessel was involved. CONCLUSION: Patients who have
      circulating antiphospholipid antibodies are at risk for major abdominal vascular
      thromboses and organ infarction. Radiologists must be familiar with this
      syndrome; they may be the first physicians to suggest the diagnosis on the basis
      of findings of unusual or recurrent sites of thrombosis, especially in young
      patients.

PMID- 11230655
TI  - Case 32: Herniation of the ascending colon into the lesser sac.

PMID- 11230656
TI  - Metastatic lymph nodes in patients with cervical cancer: detection with MR
      imaging and FDG PET.
AB  - PURPOSE: To compare the diagnostic accuracy of magnetic resonance (MR) imaging
      with that of positron emission tomography (PET) with 2-[fluorine 18]fluoro-2
      deoxy-D-glucose (FDG) for detecting metastatic lymph nodes in patients with
      cervical cancer. MATERIALS AND METHODS: Before radical hysterectomy and pelvic
      lymphadenectomy in 35 patients with International Federation of Gynecology and
      Obstetrics stage IB or II cervical cancer, abdominal FDG-PET and MR imaging were
      performed. Malignancy criteria were a lymph node diameter of 1 cm or more at MR
      imaging and a focally increased FDG uptake at PET. The findings of FDG-PET and MR
      imaging were compared with histologic findings. RESULTS: Histologic examination
      revealed pN0-stage cancer in 24 patients and pN1-stage cancer in 11 patients. On
      a patient basis, node staging resulted in sensitivities of 0.91 with FDG-PET and
      0.73 with MR imaging and specificities of 1.00 with FDG-PET and 0.83 with MR
      imaging. The positive predictive value (PPV) of FDG-PET was 1.00 and that of MR
      imaging, 0.67 (not significant). The metastatic involvement of lymph node sites
      was identified at FDG-PET with a PPV of 0.90; at MR imaging, 0.64 (P <.05, Fisher
      exact test). CONCLUSION: Metabolic imaging with FDG-PET is an alternative to
      morphologic MR imaging for detecting metastatic lymph nodes in patients with
      cervical cancer.

PMID- 11230657
TI  - Comparison between MR imaging and 99mTc MIBI scintigraphy in the evaluation of
      recurrent of persistent hyperparathyroidism.
AB  - PURPOSE: To compare the sensitivity and positive predictive value of magnetic
      resonance (MR) imaging and technetium 99m 2-methoxyisobutyl-isonitrile (MIBI)
      scintigraphy for the detection of hyperfunctioning parathyroid tissue when used
      alone and in combination in a large patient population with recurrent or
      persistent hyperparathyroidism (HPT). MATERIALS AND METHODS: In 98 consecutive
      patients with biochemically proved recurrent or persistent HPT after surgery, MR
      imaging and 99mTc MIBI study findings were retrospectively reviewed and compared
      with surgical and histopathologic findings. The sensitivity and positive
      predictive value of MR imaging and 99mTc MIBI scintigraphy were compared with
      each other and in combination. RESULTS: In these patients, 130 abnormal
      parathyroid glands were identified at surgery. The sensitivity and positive
      predictive value of MR imaging were 82% (95% CI: 75%, 89%) and 89%, respectively;
      those for (99m)Tc MIBI scintigraphy were 85% (95% CI: 79%, 91%) and 89%. No
      significant difference was found between MR imaging and 99mTc MIBI scintigraphy
      for sensitivity (P =.7). The sensitivity and positive predictive value for the
      detection of abnormal parathyroid tissue on a per-gland basis increased to 94%
      (95% CI: 90%, 98%) and 98%, respectively, when only one of the two tests was
      required to be positive. CONCLUSION: MR imaging and 99mTc MIBI scintigraphy have
      similarly good sensitivity and positive predictive value for the detection of
      hyperfunctioning parathyroid tissue in patients after surgery. The combination of
      the two tests provided a substantial increase in sensitivity and positive
      predictive value.

PMID- 11230658
TI  - Evaluation of a reduced MR imaging sequencing protocol in adult patients with
      stroke.
AB  - PURPOSE: To compare a reduced (three-sequence) magnetic resonance (MR) imaging
      protocol with a full (eight- to 10-sequence) MR imaging protocol in adults
      suspected of having stroke. MATERIALS AND METHODS: Six neuroradiologists
      interpreted a consecutive sample of 265 MR images in patients suspected of having
      stroke. Each read reduced-protocol images in a discrete series of 40 patients
      (one read images in only 15) and corresponding full-protocol images 1 month later
      (reduced/full protocol). Five of the readers each read images in 10 additional
      cases, five each as full/full and reduced/reduced protocol controls. kappa values
      between full and reduced protocols, reader assessment of protocol adequacy,
      confidence level, and need for additional sequences or examinations were
      evaluated. RESULTS: In the reduced/full protocol, the kappa value for detecting
      ischemia was 0.797; and that for detecting any clinically important abnormality,
      0.635. Statistically similar kappa values were found with the full/full control
      design (kappa = 0.802 and 0.715, respectively). The full protocol was judged more
      adequate than the reduced protocol (2.0 of 5.0 points vs 1.6, P <.001) and
      generated greater diagnostic confidence (8.6 of 10.0 points vs 8.9, P =.01), less
      need for additional sequences (2.7 of 6.0 points vs 1.5, P <.001), and more
      requests for additional examinations (28.4% vs 36.3%). CONCLUSION: Disagreement
      between interpretations of reduced- and full-protocol images might be
      attributable to baseline-level intraobserver inconsistency, as demonstrated in
      control designs. A greater number of sequences did not lead to greater
      consistency.

PMID- 11230659
TI  - Intracranial aneurysms: clinical value of 3D digital subtraction angiography in
      the therapeutic decision and endovascular treatment.
AB  - PURPOSE: To evaluate three-dimensional (3D) digital subtraction angiography (DSA)
      as a supplement to two-dimensional (2D) DSA in the endovascular treatment (EVT)
      of intracranial aneurysms. MATERIALS AND METHODS: In 22 ruptured aneurysms, neck
      visualization, aneurysm shape, and EVT feasibility were analyzed at 2D DSA
      (anteroposterior, lateral, and rotational views) and at maximum intensity
      projection (MIP) and surface shaded display (SSD) 3D DSA. The possibility of
      obtaining a working view for EVT at 3D DSA and the relevance of measurements in
      choosing the first coil also were assessed. RESULTS: Two-dimensional DSA images
      clearly depicted the aneurysm neck in four of 22 aneurysms; MIP images, in 10;
      and SSD images, in 21, but SSD led to overestimation of the neck size in one
      aneurysm. Aneurysm shape was precisely demonstrated in five of 22 aneurysms at 2D
      DSA, in eight at MIP, and in all cases at SSD. In two of 22 aneurysms, EVT seemed
      to be nonfeasible at 2D DSA; however, SSD demonstrated feasibility and EVT was
      successfully performed. In one aneurysm, only SSD demonstrated the extension of
      the neck to a parent vessel, which was proved at surgery. Working views for EVT
      were deduced from 3D DSA findings in 20 of 21 aneurysms. The choice of the first
      coil was correct in 19 of 21 aneurysms. CONCLUSION: Three-dimensional DSA is
      valuable for evaluating the potential for EVT, finding a working view, and
      performing accurate measurements.

PMID- 11230660
TI  - Evaluation of white matter anisotropy in Krabbe disease with diffusion tensor MR
      imaging: initial experience.
AB  - PURPOSE: To compare diffusion tensor magnetic resonance imaging with conventional
      T2-weighted imaging for evaluation of white matter changes in patients with
      Krabbe disease. MATERIALS AND METHODS: In eight patients with Krabbe disease and
      eight age-matched control subjects, anisotropy maps were generated with diffusion
      tensor data by using echo-planar imaging with diffusion gradient encoding in six
      directions. Anisotropy maps and T2-weighted images were visually inspected.
      Relative anisotropy (RA) and normalized T2-weighted signal intensity in white
      matter tracts and gray matter nuclei were quantitatively compared between
      patients and controls (paired Student t test). RESULTS: Loss of diffusion
      anisotropy appeared on anisotropy maps as areas of decreased hyperintensity in
      patients with Krabbe disease. Differences in RA between Krabbe disease patients
      and control subjects were significant in eight of nine white matter structures
      studied (P =.001-.01) and in basal ganglia (P =.04). T2-weighted signal intensity
      was also significantly different in the same white matter structures (P =.006
      .049) but not in basal ganglia. In the three patients imaged after stem cell
      transplantation, mean RA was between the RAs of untreated patients and control
      subjects. CONCLUSION: Diffusion tensor-derived anisotropy maps (a) provide a
      quantitative measure of abnormal white matter in patients with Krabbe disease,
      (b) are more sensitive than T2-weighted images for detecting white matter
      abnormality, and (c) may be a marker of treatment response.

PMID- 11230661
TI  - Perioperative transcranial Doppler US to evaluate intracranial compliance in
      young children undergoing craniosynostosis repair surgery.
AB  - PURPOSE: To determine whether measurements with transcranial Doppler
      ultrasonography (US) of resistive indexes (RIs) of basal cerebral arteries with
      pressure provocation can be used to identify infants and children with
      craniosynostosis who have abnormal intracranial compliance and to study the
      effects of surgery on compliance. MATERIALS AND METHODS: Transcranial Doppler US
      was performed through the temporal squama, fontanels, and existing skull defects
      prior to and immediately following cranioplasty. Twenty-four studies were
      performed in six patients with multisuture synostosis, and 61 studies were
      performed in 26 patients with single-suture synostosis. Study findings were
      compared with those of 23 control subjects and were characterized as normal or
      abnormal on the basis of age-specific normal criteria for RI. RESULTS: In
      multisuture synostosis, results of six of the nine preoperative transcranial
      Doppler US studies were abnormal. During postoperative follow-up, three
      recurrences requiring reoperation occurred, one of which was detected with
      abnormal transcranial Doppler US findings. In single-suture synostosis, results
      of seven of the 26 preoperative transcranial Doppler US studies were abnormal,
      and all occurred in young infants with sagittal and unicoronal synostosis.
      Immediate effects of surgery were variable. All patients with sagittal synostosis
      had a significant immediate postoperative increase in RI, which normalized during
      postoperative follow-up. There was no significant difference in RI between
      patients with successfully treated craniosynostosis and control subjects.
      CONCLUSION: Transcranial Doppler US can be used to identify patients with
      craniosynostosis with decreased intracranial compliance, and it is a suitable
      noninvasive test to monitor the effects of surgery on compliance.

PMID- 11230663
TI  - Quantitative apparent diffusion coefficient measurements in term neonates for
      early detection of hypoxic-ischemic brain injury: initial experience.
AB  - PURPOSE: To determine the utility of using quantitative apparent diffusion
      coefficient (ADC) values as an objective means of early detection of brain injury
      caused by hypoxic-ischemic encephalopathy (HIE) in term neonates. MATERIALS AND
      METHODS: Conventional images, diffusion-weighted images, ADC maps, and clinical
      charts from 13 term neonates clinically suspected of having HIE were
      retrospectively reviewed. Four term neonates without HIE served as control
      subjects. ADC values were calculated in predefined regions in patients and
      compared with those in control subjects. A Student t test was performed for each
      region to compare patients and control subjects. RESULTS: Abnormalities were more
      easily detected on diffusion-weighted images and ADC maps, compared with
      conventional images. ADC values in patients with HIE were significantly different
      from those of control subjects in the posterior limb of the internal capsule,
      corona radiata, posterior frontal white matter, and parietal white matter
      bilaterally. CONCLUSION: Evaluation of ADC maps can improve conspicuity of
      hypoxic-ischemic injury in the acute and/or subacute setting (within 12 days of
      insult), and calculation of ADC values can provide an objective measure of
      hypoxic-ischemic injury.

PMID- 11230664
TI  - Radiation therapy for life- or function-threatening infant hemangioma.
AB  - PURPOSE: To assess the effectiveness and long-term results of radiation therapy
      in infants with life- or function-threatening hemangiomas. MATERIALS AND METHODS:
      Thirteen patients with life- or function-threatening hemangiomas (eight male,
      five female; age range, 0-8 months; median age, 2 months) were treated with
      radiation therapy. Life-threatening hemangiomas were treated with five fractions
      of radiation per week, and function-threatening hemangiomas were treated with two
      fractions per week. A median dose of 10 Gy was delivered to each hemangioma. The
      presence of residual hemangiomas, skin changes, functional problems, and growth
      delay was evaluated. RESULTS: All patients with Kasabach-Merritt syndrome (KMS)
      showed regression of the hemangioma and an increase in platelet counts to greater
      than 100,000 per cubic millimeter (1.0 x 10(11) per liter) within 40 days after
      radiation therapy. The treatment field was inadequate in two patients who
      required reirradiation or a change of treatment portal. With the exception of the
      patients with KMS, all but one patient experienced relief from symptoms in 40
      days. Severe long-term radiation-related morbidity was noted in one patient who
      required reirradiation for a relapsed hemangioma. CONCLUSION: Radiation therapy
      (in doses of < or = 10 Gy in 2-Gy fractions) is indicated for life-threatening
      hemangiomas and for some function-threatening hemangiomas.

PMID- 11230665
TI  - Hemangiomas of the fingers: MR imaging evaluation.
AB  - PURPOSE: To report the magnetic resonance (MR) imaging features of finger
      hemangiomas. MATERIALS AND METHODS: Sixteen patients clinically suspected of
      having hemangioma of the finger underwent 1.5-T MR imaging with a customized
      local gradient coil. The location, size, margins, signal intensity, and
      enhancement patterns of the lesions were noted. In accordance with the literature
      on MR imaging of deep hemangiomas, the authors' findings could be divided into
      those with typical features-that is, high signal intensity at T1- and T2-weighted
      imaging, lobulated appearance, strong enhancement, and heterogeneous pattern with
      flow void artifacts-and those with atypical features. The reference standard was
      surgery (n = 12) or clinical outcome (n = 4). RESULTS: One posttraumatic hematoma
      was excluded. Most lesions were in the fingertip (n = 10), with involvement of
      the nail bed and/or the pulp (n = 5). Hemangiomas were classified as typical in
      ten cases and atypical in five. The mean size of typical lesions was larger than
      that of atypical lesions. The unique imaging features of atypical hemangiomas
      included a masslike appearance, which was either homogeneous with diffuse
      enhancement-suggestive of hypervascularity (n = 2)-or heterogeneous with poor
      enhancement (n = 3). CONCLUSION: MR imaging characteristics of finger hemangiomas
      can be classified as typical or atypical. Knowledge of both patterns can be
      helpful in the distinction of soft-tissue abnormalities at this location.

PMID- 11230666
TI  - Tuberculous versus pyogenic arthritis: MR imaging evaluation.
AB  - PURPOSE: To assess magnetic resonance (MR) imaging features in differentiating
      tuberculous arthritis from pyogenic arthritis. MATERIALS AND METHODS: Findings in
      29 patients with tuberculous arthritis were compared with those of 13 patients
      with pyogenic arthritis. Bone erosion, marrow signal intensity, synovial lesion
      signal intensity, boundaries (smooth or irregular) for extraarticular extension
      of infection, and abscess rim enhancement (thin and smooth or thick and
      irregular) were analyzed. RESULTS: Bone erosion was more common in patients with
      tuberculous arthritis (24 [83%] of 29) than in those with pyogenic arthritis (six
      [46%] of 13) (P =.026), while subchondral marrow signal intensity abnormality was
      seen more frequently in patients with pyogenic arthritis (12 [92%] of 13) than in
      those with tuberculous arthritis (17 [59%] of 29) (P =.036). On T2-weighted
      images, there was no significant difference between the synovial lesion signal
      intensities of tuberculous arthritis and pyogenic arthritis. Lesions in 16 (70%)
      of 23 patients with tuberculous arthritis and two (17%) of 12 patients with
      pyogenic arthritis had smooth extraarticular boundaries, while those in seven
      (30%) of 23 patients with tuberculous arthritis and 10 (83%) of 12 patients with
      pyogenic arthritis had irregular boundaries (P =.005). Tuberculous abscesses (16
      [100%] of 16) had thin and smooth rim enhancement, while most pyogenic abscesses
      (five [71%] of seven) had thick and irregular rims (P =.001). CONCLUSION: MR
      imaging of bone abnormalities, extraarticular lesions, and associated abscesses
      provides useful information in the differentiation of tuberculous arthritis and
      pyogenic arthritis.

PMID- 11230667
TI  - Practice costs in diagnostic radiology.
AB  - PURPOSE: To report on practice costs and their variation. MATERIALS AND METHODS:
      In 1996 and 1997, practices were surveyed, and data on costs and other
      operational characteristics were obtained from approximately 170 practices.
      Several components of practice costs (eg, physician-related costs, administrative
      and business costs) were calculated separately for different group types (eg,
      academic, private hospital-only), each on four bases: per full-time equivalent
      (FTE) radiologist, per relevant procedure, per relevant relative value unit
      (RVU), and as a percentage of revenue. RESULTS: Median total practice costs per
      FTE radiologist ranged from approximately $90,000 to $190,000, depending on group
      type. Per procedure, the median ranged from $9 to $21; and as a percentage of
      revenue, it ranged from 27% to 41%. Median technical costs were approximately $36
      per technical RVU in private hospital-and-office groups. Within any category of
      group, for every cost category, there was substantial variation among groups.
      CONCLUSION: The sizable variation implies that means or medians should not be
      regarded as norms. Nonetheless, the data on 75th and 25th percentile costs can
      show a radiology group where savings and inadequate resources, respectively, are
      relatively likely to be found. Physician-related costs are best measured per FTE.
      Technical costs and administrative and business costs are best measured per RVU
      or for categories of groups defined by having similar percentages of nonhospital
      services.

PMID- 11230668
TI  - Stereotactic core-needle breast biopsy: a multi-institutional prospective trial.
AB  - PURPOSE: To assess the accuracy of stereotactic core-needle biopsy (CNB) of
      nonpalpable breast lesions within the context of clinically important parameters
      of anticipated tissue-sampling error and concordance with mammographic findings.
      MATERIALS AND METHODS: CNB was performed in 1,003 patients, with results
      validated at surgery or clinical and mammographic follow-up. Mammographic
      findings were scored according to the American College of Radiology Breast
      Imaging Reporting and Data System with a similar correlative scale for
      histopathologic samples obtained at either CNB or surgery. Agreement of CNB
      findings with surgical findings or evidence of no change during clinical and
      mammographic follow-up (median, 24 months) for benign lesions was used to
      determine results. Three forms of diagnostic discrimination measures (strict,
      working [strict conditioned by tissue sampling error], applied [working
      conditioned by concordance of imaging and CNB findings) were used to evaluate the
      correlation of CNB, surgical, and follow-up results. RESULTS: Strict, working,
      and applied sensitivities were 91% +/- 1.9; 92% +/- 1.8, and 98% +/- 0.9,
      respectively; strict, working, and applied specificities were 100%, 98% +/- 0.8,
      and 73% +/- 0.9; strict, working, and applied accuracies were 97%, 96%, and 79%.
      CONCLUSION: Percutaneous stereotactic CNB is an accurate method to establish a
      histopathologic diagnosis of nonpalpable breast lesions. Accuracy increases when
      additional surgery is performed for lesions with anticipated sampling error or
      when CNB findings are discordant with mammographic findings. An understanding of
      the interrelationship among these parameters is necessary to properly assess
      results.

PMID- 11230669
TI  - Comparison of full-field digital mammography with screen-film mammography for
      cancer detection: results of 4,945 paired examinations.
AB  - PURPOSE: To prospectively compare full-field digital mammography (FFDM) with
      screen-film mammography (SFM) for cancer detection in a screening population.
      MATERIALS AND METHODS: At two institutions, 4,945 FFDM examinations were
      performed in women aged 40 years and older presenting for SFM. Two views of each
      breast were acquired with each modality. SFM and FFDM images were interpreted
      independently. Findings detected with either SFM or FFDM were evaluated with
      additional imaging and, if warranted, biopsy. RESULTS: Patients in the study
      underwent 152 biopsies, which resulted in the diagnosis of 35 breast cancers.
      Twenty-two cancers were detected with SFM and 21 with FFDM. Four were interval
      cancers that became palpable within 1 year of screening and were considered false
      negative findings with both modalities. The difference in cancer detection rate
      was not significant. FFDM had a significantly lower recall rate (11.5%; 568 of
      4,945) than SFM (13.8%; 685 of 4,945) (P <.001, McNemar chi(2) model; P <.03,
      generalized estimating equations model). The positive biopsy rate for findings
      detected with FFDM (30%; 21 of 69) was higher than that for findings detected
      with SFM (19%; 22 of 114), but this difference was not significant. CONCLUSION:
      No difference in cancer detection rate has yet been observed between FFDM and
      SFM. FFDM has so far led to fewer recalls than SFM.

PMID- 11230670
TI  - Stereotactic core biopsy breast and blood cell by-products: a source of material
      for molecular genetics research--initial experience.
AB  - Stereotactic core biopsy washings and blood drop samples, routinely discarded by
      products, provide satisfactory fresh cellular material for flow cytometry and
      molecular genetics microsatellite polymerase chain reaction (PCR) analysis for
      detection of loss of DNA alleles (loss of heterozygosity). Cytokeratin-positive
      (epithelial) cells from the core biopsy washings were sorted by means of flow
      cytometry prior to PCR analysis. DNA allele loss was detected in benign breast
      epithelial cells in three (20%) of 15 patients.

PMID- 11230672
TI  - CT angiography of the circle of Willis and intracranial internal carotid
      arteries: maximum intensity projection with matched mask bone elimination
      feasibility study.
AB  - Results are reported of a feasibility study in which bone pixels are eliminated
      from computed tomographic (CT) angiographic images with a method that enables the
      construction of maximum intensity projection (MIP) images without interference by
      bone. The method proved to be successful in six patients. Two observers blinded
      to the bone elimination method judged the image quality of MIP images to be
      considerably higher than that of standard subtraction MIP images. This method is
      an effective means to remove bone from CT angiographic images with only a slight
      increase in radiation dose.

PMID- 11230671
TI  - Chronic cervical radiculopathy: lateral-approach periradicular corticosteroid
      injection.
AB  - Thirty-two patients underwent periradicular corticosteroid injections with a
      lateral percutaneous approach under fluoroscopic guidance, to treat 34 foci of
      chronic cervical radiculopathy unresponsive to medical treatment alone. The mean
      evolutionary trends for radicular and neck pain relief were significant at 14
      days (P <.001) and at 6 months (P <.001). The procedure did not produce any
      complications.

PMID- 11230673
TI  - Anatomically tailored k-Space sampling for bolus-chase three-dimensional MR
      digital subtraction angiography.
AB  - The purpose of this study was to evaluate a variable k-space sampling method for
      bolus-chase three-dimensional magnetic resonance digital subtraction angiography
      in the arterial system from the abdomen to the calf. Imaging time was minimized
      by tailoring the acquisition according to the vascular anatomy of the station.
      For images obtained in 30 patients, results with the modified protocol were
      compared to those with the previously published protocol. For all stations,
      significant improvement (P <.001) was found with the modified protocol.

PMID- 11230674
TI  - An electronic device for needle placement during sonographically guided
      percutaneous intervention.
AB  - An electronic device for guiding needle placement during sonographically directed
      percutaneous intervention was tested in a phantom and then in patients. In the
      phantom, targeting accuracy was similar for use of the needle guide alone, the
      needle guide with the device, and freehand techniques with the device, but all
      were superior to the freehand technique alone (P <.001). In 34 (79%) of 43
      patients, the device worked well.

PMID- 11230675
TI  - Use of imaging for the diagnosis of pulmonary embolism.

PMID- 11230676
TI  - Meaning of a helical CT angiogram negative for pulmonary embolism.

PMID- 11230677
TI  - Localization of parathyroid nodules.

PMID- 11230678
TI  - Reporting radiation dose for uterine artery embolization.

PMID- 11230679
TI  - Radio-frequency ablation of hepatocellular carcinoma lesions.

PMID- 11230686
TI  - Spins in the vortices of a high-temperature superconductor.
AB  - Neutron scattering is used to characterize the magnetism of the vortices for the
      optimally doped high-temperature superconductor La(2-x)Sr(x)CuO4 (x = 0.163) in
      an applied magnetic field. As temperature is reduced, low-frequency spin
      fluctuations first disappear with the loss of vortex mobility, but then reappear.
      We find that the vortex state can be regarded as an inhomogeneous mixture of a
      superconducting spin fluid and a material containing a nearly ordered
      antiferromagnet. These experiments show that as for many other properties of
      cuprate superconductors, the important underlying microscopic forces are
      magnetic.

PMID- 11230685
TI  - An iron-regulated ferric reductase associated with the absorption of dietary
      iron.
AB  - The ability of intestinal mucosa to absorb dietary ferric iron is attributed to
      the presence of a brush-border membrane reductase activity that displays adaptive
      responses to iron status. We have isolated a complementary DNA, Dcytb (for
      duodenal cytochrome b), which encoded a putative plasma membrane di-heme protein
      in mouse duodenal mucosa. Dcytb shared between 45 and 50% similarity to the
      cytochrome b561 family of plasma membrane reductases, was highly expressed in the
      brush-border membrane of duodenal enterocytes, and induced ferric reductase
      activity when expressed in Xenopus oocytes and cultured cells. Duodenal
      expression levels of Dcytb messenger RNA and protein were regulated by changes in
      physiological modulators of iron absorption. Thus, Dcytb provides an important
      element in the iron absorption pathway.

PMID- 11230687
TI  - Submicrometer patterning of charge in thin-film electrets.
AB  - Thin-film electrets have been patterned with trapped charge with submicrometer
      resolution using a flexible, electrically conductive electrode. A
      poly(dimethylsiloxane) stamp, patterned in bas-relief and supporting an 80
      nanometer-thick gold film, is brought into contact with an 80-nanometer-thick
      film of poly(methylmethacrylate) supported on n-doped silicon. A voltage pulse
      between the gold film and the silicon transfers charge at the contact areas
      between the gold and the polymer electret. Areas as large as 1 square centimeter
      were patterned with trapped charges at a resolution better than 150 nanometers in
      less than 20 seconds. This process provides a new method for patterning; it
      suggests possible methods for high-density, charge-based data storage and for
      high-resolution charge-based printing.

PMID- 11230688
TI  - Fluorous mixture synthesis: a fluorous-tagging strategy for the synthesis and
      separation of mixtures of organic compounds.
AB  - The solution-phase synthesis of organic compounds as mixtures rather than in
      individual pure form offers efficiency advantages that are negated by the
      difficulty in separating and identifying the components of the final mixture.
      Here, a strategy for mixture synthesis that addresses these separation and
      identification problems is presented. A series of organic substrates was tagged
      with a series of fluorous tags of increasing fluorine content. The compounds were
      then mixed, and multistep reactions were conducted to make enantiomers or analogs
      of the natural product mappicine. The resulting tagged products were then demixed
      by fluorous chromatography (eluting in order of increasing fluorine content) to
      provide the individual pure components of the mixture, which were detagged to
      release the final products.

PMID- 11230689
TI  - Reversible surface morphology changes of a photochromic diarylethene single
      crystal by photoirradiation.
AB  - The surface morphology of a diarylethene single crystal [1,2-bis(2,4-dimethyl-5
      phenyl-3-thienyl)perfluorocyclopentene] determined by atomic force microscopy
      changed reversibly upon photoirradiation. The crystal underwent a thermally
      irreversible but photochemically reversible color change (colorless to blue) upon
      alternate irradiation with ultraviolet (wavelength lambda = 366 nm) and visible
      (lambda > 500 nm) light that drove reversible photocyclization reactions. Upon
      irradiation with 366-nm light, new steps appeared on the (100) single-crystalline
      surface that disappeared upon irradiation with visible light (lambda > 500 nm).
      The step height, about 1 nm, corresponds to one molecular layer. Irradiation with
      366-nm light formed valleys on the (010) surface that also disappeared by
      bleaching upon irradiation with visible light (lambda > 500 nm). The surface
      morphological changes can be explained by the molecular structural changes of
      diarylethenes regularly packed in the single crystal. These crystals could
      potentially be used as photodriven nanometer-scale actuators.

PMID- 11230690
TI  - Ablation, flux, and atmospheric implications of meteors inferred from
      stratospheric aerosol.
AB  - Single-particle analyses of stratospheric aerosol show that about half of the
      particles contain 0.5 to 1.0 weight percent meteoritic iron by mass, requiring a
      total extraterrestrial influx of 8 to 38 gigagrams per year. The sodium/iron
      ratio in these stratospheric particles is higher and the magnesium/iron and
      calcium/iron ratios are lower than in chondritic meteorites, implying that the
      fraction of material that is ablated must lie at the low end of previous
      estimates and that the extraterrestrial component that resides in the mesosphere
      and stratosphere is not of chondritic composition.

PMID- 11230691
TI  - A new astrophysical setting for chondrule formation.
AB  - Chondrules in the metal-rich meteorites Hammadah al Hamra 237 and QUE 94411 have
      recorded highly energetic thermal events that resulted in complete vaporization
      of a dusty region of the solar nebula (dust/gas ratio of about 10 to 50 times
      solar). These chondrules formed under oxidizing conditions before condensation of
      iron-nickel metal, at temperatures greater than or equal to 1500 K, and were
      isolated from the cooling gas before condensation of moderately volatile elements
      such as manganese, sodium, potassium, and sulfur. This astrophysical environment
      is fundamentally different from conventional models for chondrule formation by
      localized, brief, repetitive heating events that resulted in incomplete melting
      of solid precursors initially residing at ambient temperatures below
      approximately 650 K.

PMID- 11230692
TI  - High geomagnetic intensity during the mid-Cretaceous from Thellier analyses of
      single plagioclase crystals.
AB  - Recent numerical simulations have yielded the most efficient geodynamo, having
      the largest dipole intensity when reversal frequency is low. Reliable
      paleointensity data are limited but heretofore have suggested that reversal
      frequency and paleointensity are decoupled. We report data from 56 Thellier
      Thellier experiments on plagioclase crystals separated from basalts of the
      Rajmahal Traps (113 to 116 million years old) of India that formed during the
      Cretaceous Normal Polarity Superchron. These data suggest a time-averaged
      paleomagnetic dipole moment of 12.5 +/- 1.4 x 10(22) amperes per square meter,
      three times greater than mean Cenozoic and Early Cretaceous-Late Jurassic dipole
      moments when geomagnetic reversals were frequent. This result supports a
      correlation between intervals of low reversal frequency and high geomagnetic
      field strength.

PMID- 11230693
TI  - An antimicrobial peptide gene found in the male reproductive system of rats.
AB  - Little is known about the innate defense mechanisms of the male reproductive
      tract. We cloned a 385-base pair complementary DNA and its genomic DNA named
      Bin1b that is exclusively expressed in the caput region of the rat epididymis and
      that is responsible for sperm maturation, storage, and protection. Bin1b exhibits
      structural characteristics and antimicrobial activity similar to that of cationic
      antimicrobial peptides, beta-defensins. Bin1b is maximally expressed when the
      rats are sexually mature and can be up-regulated by inflammation. Bin1b appears
      to be a natural epididymis-specific antimicrobial peptide that plays a role in
      reproductive tract host defense and male fertility.

PMID- 11230694
TI  - Molecular and morphological supertrees for eutherian (placental) mammals.
AB  - A large body of diverse comparative data now exists for a major phylogenetic
      synthesis of the higher-level relationships among eutherian (placental) mammals.
      We present such a phylogenetic synthesis using the composite trees or supertrees
      from the combined and separate analyses of their published molecular and
      morphological source phylogenies. Our combined and separate supertrees largely
      support the same suprafamilial taxa and orders, but different interordinal
      clades. These similarities and differences reinforce the continuing contributions
      of morphological studies, while highlighting the growing influence of molecular
      information on the field. As current summaries of past research, our supertrees
      emphasize opportunities for future work, while providing a step toward the
      eventual integration of the data and characters themselves.

PMID- 11230696
TI  - Structural mechanism of endosome docking by the FYVE domain.
AB  - The recruitment of trafficking and signaling proteins to membranes containing
      phosphatidylinositol 3-phosphate [PtdIns(3)P] is mediated by FYVE domains. Here,
      the solution structure of the FYVE domain of the early endosome antigen 1 protein
      (EEA1) in the free state was compared with the structures of the domain complexed
      with PtdIns(3)P and mixed micelles. The multistep binding mechanism involved
      nonspecific insertion of a hydrophobic loop into the lipid bilayer, positioning
      and activating the binding pocket. Ligation of PtdIns(3)P then induced a global
      structural change, drawing the protein termini over the bound phosphoinositide by
      extension of a hinge. Specific recognition of the 3-phosphate was determined
      indirectly and directly by two clusters of conserved arginines.

PMID- 11230695
TI  - Biosynthesis of complex polyketides in a metabolically engineered strain of E.
      coli.
AB  - The macrocyclic core of the antibiotic erythromycin, 6-deoxyerythronolide B
      (6dEB), is a complex natural product synthesized by the soil bacterium
      Saccharopolyspora erythraea through the action of a multifunctional polyketide
      synthase (PKS). The engineering potential of modular PKSs is hampered by the
      limited capabilities for molecular biological manipulation of organisms
      (principally actinomycetes) in which complex polyketides have thus far been
      produced. To address this problem, a derivative of Escherichia coli has been
      genetically engineered. The resulting cellular catalyst converts exogenous
      propionate into 6dEB with a specific productivity that compares well with a high
      producing mutant of S. erythraea that has been incrementally enhanced over
      decades for the industrial production of erythromycin.

PMID- 11230697
TI  - Living with genome instability: plant responses to telomere dysfunction.
AB  - Loss of telomere function in metazoans results in catastrophic damage to the
      genome, cell cycle arrest, and apoptosis. Here we show that the mustard weed
      Arabidopsis thaliana can survive up to 10 generations without telomerase. The
      last five generations of telomerase-deficient plants endured increasing levels of
      cytogenetic damage, which was correlated with developmental anomalies in both
      vegetative and reproductive organs. Mutants ultimately arrested at a terminal
      vegetative state harboring shoot meristems that were grossly enlarged,
      disorganized, and in some cases, dedifferentiated into a callusoid mass.
      Unexpectedly, late-generation mutants had an extended life-span and remained
      metabolically active. The differences in plant and animal responses to
      dysfunctional telomeres may reflect the more plastic nature of plant development
      and genome organization.

PMID- 11230698
TI  - Role of the sphingosine-1-phosphate receptor EDG-1 in PDGF-induced cell motility.
AB  - EDG-1 is a heterotrimeric guanine nucleotide binding protein-coupled receptor
      (GPCR) for sphingosine-1-phosphate (SPP). Cell migration toward platelet-derived
      growth factor (PDGF), which stimulates sphingosine kinase and increases
      intracellular SPP, was dependent on expression of EDG-1. Deletion of edg-1 or
      inhibition of sphingosine kinase suppressed chemotaxis toward PDGF and also
      activation of the small guanosine triphosphatase Rac, which is essential for
      protrusion of lamellipodia and forward movement. Moreover, PDGF activated EDG-1,
      as measured by translocation of beta-arrestin and phosphorylation of EDG-1. Our
      results reveal a role for receptor cross-communication in which activation of a
      GPCR by a receptor tyrosine kinase is critical for cell motility.

PMID- 11230699
TI  - The role of working memory in visual selective attention.
AB  - The hypothesis that working memory is crucial for reducing distraction by
      maintaining the prioritization of relevant information was tested in neuroimaging
      and psychological experiments with humans. Participants performed a selective
      attention task that required them to ignore distractor faces while holding in
      working memory a sequence of digits that were in the same order (low memory load)
      or a different order (high memory load) on every trial. Higher memory load,
      associated with increased prefrontal activity, resulted in greater interference
      effects on behavioral performance from the distractor faces, plus increased face
      related activity in the visual cortex. These findings confirm a major role for
      working memory in the control of visual selective attention.

PMID- 11230700
TI  - Informatics and anatomic pathology: meeting challenges and charting the future.

PMID- 11230701
TI  - Overexpression of neural cell adhesion molecule in Chagas' myocarditis.
AB  - The expression of the neural cell adhesion molecule (NCAM) was studied in normal
      human myocardium and in Chagas' disease myocarditis. We found that NCAM is
      expressed in the conduction system as well as the myocardium in the fetal heart,
      but its expression is restricted to the conduction system and absent in the adult
      myocardium. Chagas' disease is an American endemic disease caused by the
      Trypanosoma cruzi parasite, which produces myocarditis and a blockade of the
      conduction system, resulting in cardiac dysfunction. We studied the expression of
      NCAM in paraffin-embedded human heart tissues from 34 autopsies of patients with
      Chagas' myocarditis and from murine and canine experimental acute Chagas'
      myocarditis, using a polyclonal anti-NCAM antibody and immunohistochemistry. Our
      results show a dramatic upregulation of NCAM expression in the intercalated discs
      of cardiomyocytes in acute and chronic Chagas' myocarditis. Surprisingly, the
      NCAM signal was detected in intracellular nests of amastigote forms of the
      parasite, within infected cardiomyocytes of human and experimental Chagas'
      myocarditis. In contrast, cardiac cell-cell adhesion proteins, N-cadherin and
      beta-catenin, were found in intercalated discs distorted by the infection but
      absent from the amastigote nests. Proteins reactive to several antibodies against
      NCAM were detected by Western immunoblotting in cultured T cruzi parasites and in
      trypomastigote forms of T cruzi extracted from the blood of infected mice. The
      upregulation of NCAM in Chagas' myocarditis and the expression of NCAM or a NCAM
      like protein by T cruzi suggest that NCAM may act as a receptor for tissue
      targeting and cellular invasion by T cruzi in Chagas' disease.

PMID- 11230702
TI  - A role for fluorescence in situ hybridization detection of chromosome 22q dosage
      in distinguishing atypical teratoid/rhabdoid tumors from medulloblastoma/central
      primitive neuroectodermal tumors.
AB  - It has been postulated that infants with medulloblastomas/central primitive
      neuroectodermal tumors (MB/PNET) may fare worse than older patients because some
      of them harbor unrecognized atypical teratoid/rhabdoid tumors (AT/RT), rare
      intracranial neoplasms that are typically unresponsive to therapy and rapidly
      fatal. Although small primitive cells are common to both entities, chromosome
      22q11.2 deletions are common only in AT/RTs. Using fluorescence in situ
      hybridization (FISH) on archival, paraffin-embedded biopsy tissue with
      commercially available probes to 22q11.2, the region associated with RTs, we
      studied 8 cases of AT/RT, 12 cases of MB/PNET, and 4 cases of primitive central
      nervous system (CNS) neoplasms, which were difficult to classify. 22q Deletions
      were identified in 6 of 8 (75%) conventional AT/RTs and 0 of 12 (0%) children
      with classic MB/PNET. Of the 4 originally "difficult to classify" cases, 3 had
      deletions of 22q. In light of the FISH results, review of the morphology and
      immunophenotype resulted in 3 tumors being reclassified as AT/RTs and 1 as a
      large cell MB. These 4 cases highlight the potential diagnostic use of FISH for
      selected cases of primitive CNS malignancies in children and substantiate the
      notion that misdiagnosed AT/RTs may, in part account for the worse prognosis
      associated with "MB/PNET" in children younger than 2 years of age.

PMID- 11230703
TI  - Clarification of the active gelatinolytic sites in human ovarian neoplasms using
      in situ zymography.
AB  - Tissues from 26 human ovarian common epithelial tumors were examined to determine
      where and how gelatinolytic activity was present, in relation to tumor-stromal
      interaction and histologic types. For this purpose, we used in situ zymography, a
      newly developed technique using gelatin-coated film. Gelatinolytic activity was
      evident in ovarian carcinomas and in borderline tumors. Benign tumors had no or
      only weak activity. Four tissue localization patterns of gelatinolysis were
      identified: pattern A, tumor cytoplasm; pattern B, tumor-stromal junction;
      pattern C, stroma; and pattern D, cystic fluid. Mucinous cystadenocarcinomas
      showed A and/or D patterns. One mucinous and one serous adenocarcinoma and one
      mucinous borderline tumor had a B pattern. Most serous and all clear cell
      adenocarcinomas showed strong gelatinolysis of C pattern, especially in the
      desmoplastic stroma, an area where the tumor cells were dispersed.
      Immunohistochemically in 12 adenocarcinomas and 3 borderline tumors, the tumor
      cytoplasm was positive for matrix metalloproteinases (MMP-2) (5 cases), MMP-7 (9
      cases), and MMP-9 (6 cases). Stromal components were positive for MMP-2 in 5
      cases and for MMP-9 in 3 cases, but they were not positive for MMP-7. MMP
      antigens were mostly distributed in an almost identical pattern consistent with
      that seen with in situ zymography. In situ zymography clarified the cellular
      localization of active gelatinolysis in human ovarian neoplasms, a finding which
      supports the view that interaction between tumor and stroma is critical for tumor
      growth. This newly developed method contributes to a better understanding of
      biologic features of ovarian malignancies.

PMID- 11230704
TI  - Deletions of chromosome 4 occur early during the pathogenesis of colorectal
      carcinoma.
AB  - Allelic losses at one or both arms of chromosome 4 are frequent in several tumor
      types, but information about colorectal carcinoma is limited. We have previously
      defined 4 nonoverlapping regions of frequent deletions in several tumor types. In
      an effort to more precisely locate the putative tumor suppressor gene(s) on
      chromosome 4 involved in the multistage pathogenesis of colorectal carcinomas, we
      performed loss of heterozygosity (LOH) studies using 19 polymorphic
      microsatellite markers. After precise microdissection of archival surgical cases,
      we determined LOH in DNA obtained from 23 colorectal adenocarcinomas, 20
      colorectal adenomas, and from corresponding histologically normal-appearing
      colonic epithelial samples adjacent to the tumors and at the resection margins.
      We observed localized deletions of chromosome 4 at multiple regions in both
      carcinomas and adenomas. We identified deletions at 4 previously identified
      regions: R1 at 4q33-34 (18%-33%), R2 at 4q25-26 (45%-65%), R3 at 4p15.1-15.3 (35%
      47%), and R4 at 4p16.3 (40%-49%). Six of fifteen (40%) cases examined with
      deletions of chromosome 4 in either adenocarcinomas or adenomas had loss of the
      same parental alleles in adjacent histologically normal epithelium but not in
      epithelial samples from the surgical resection margins. The deletions, which
      commenced on the short arm of chromosome 4 (regions R3 and/or R4), were more
      extensive in adenocarcinomas, intermediate in length in adenomas, and least
      extensive in histologically normal epithelium. Our results suggest that there may
      be multiple putative tumor suppressor genes located on both arms of chromosome 4
      whose inactivation are important early events in the pathogenesis of colorectal
      carcinoma.

PMID- 11230705
TI  - Lymph nodes in the human female breast: a review of their detection and
      significance.
AB  - Our experience led us to test the hypothesis that lymph nodes are not uncommon
      within the substance of the human female breast mound. The following specimen
      types and sources were used to survey the presence of intramammary lymph nodes in
      the human female breast mound: (1) cadaver breasts; (2) community hospital breast
      specimens; and (3) university and VA hospital specimens. We found true lymph
      nodes within and associated with breast specific tissue (ie, tissue that includes
      duct and gland structures), thereby validating the hypothesis posed. We discuss
      the significance of these findings in terms of our dominant patient care paradigm
      (the Triple Test-physical examination, imaging, and fine-needle aspiration [FNA])
      and the choice of patient care management options. We conclude the following:
      lymph nodes occur in any quadrant of the breast mound; recognizing the
      possibility of intramammary lymph nodes is important when choosing between
      patient management options; intramammary lymph nodes can be sampled by FNA;
      intramammary lymph nodes can contain various disease processes; and in the Oregon
      Health Sciences University Multidisciplinary Breast Clinic, these intramammary
      lymph nodes are commonly identified by imaging methods and are more likely to be
      sampled by FNA than either by core or excisional biopsy.

PMID- 11230706
TI  - Telomerase activity and expression of human telomerase RNA component and human
      telomerase reverse transcriptase in lung carcinomas.
AB  - The aim of this study was to evaluate the usefulness of determination of
      telomerase activity and expression of human telomerase RNA component (hTERC) and
      human telomerase reverse transcriptase (hTERT) for the diagnosis of lung
      carcinomas. The tissues studied consisted of 115 carcinomas and adjacent
      nonneoplastic lung, which were removed surgically without previous chemotherapy
      or radiotherapy. Telomerase activity was determined using a semiquantitative
      polymerase chain reaction-based telomeric repeat amplification protocol (TRAP)
      assay. The results obtained were classified into high and low telomerase groups.
      Localization of expression was examined by using in situ hybridization and
      immunohistochemistry. The correlation between telomerase activity in lung
      carcinoma and clinicopathologic features, including prognosis, was investigated.
      Telomerase activity in lung carcinomas was detected in 107 of 115 (93%) lung
      carcinomas, but not in any adjacent noncancerous tissues, and was significantly
      higher in small cell carcinoma than in any other histologic type. This activity
      also was significantly higher in poorly differentiated than in well
      differentiated squamous cell carcinomas and adenocarcinomas. The overall survival
      rate (P =.020) was significantly lower in the high telomerase group. Messenger
      RNAs for hTERC and hTERT were mainly detected in the cytoplasm of cancer cells by
      in situ hybridization, and TERT protein was localized in the nuclei of these
      cells by immunohistochemical staining. Determinations of telomerase activity by
      in situ hybridization, immunohistochemistry, and TRAP assay are useful for
      evaluating the diagnosis and prognosis of lung carcinomas.

PMID- 11230707
TI  - Expression of p53 protein in T- and natural killer-cell lymphomas is associated
      with some clinicopathologic entities but rarely related to p53 mutations.
AB  - To determine if p53 abnormalities could be involved in the pathogenesis of T- or
      natural killer (NK)-cell lymphomas, we investigated 51 cases of these lymphomas
      for the expression of p53 and its relationship with p53 gene mutations, the
      expression of the p21 protein as well as the proliferative and apoptotic indices.
      Overexpression of p53 was found in 19 cases (37%), whereas mutations of the p53
      gene were observed in only 5 of 28 tested cases. The analysis of
      immunohistochemical data showed some entity-related phenotypic profiles.
      Anaplastic large cell lymphomas showed a frequent overexpression of p53 (7/8
      cases) and p21 (6/8 cases) proteins and rare p53 mutations (1/7 cases),
      suggesting accumulation of a functional wild type p53 protein able to induce p21
      expression. Nodal peripheral T-cell lymphomas unspecified showed relatively
      frequent overexpression of p53 protein (5/7 cases), infrequent p21 expression
      (2/7 cases), and rare p53 gene mutations (1/6 cases). In angioimmunoblastic
      lymphomas, the common phenotype was p53-/p21- (15/17 cases), with only a few
      scattered p53-positive cells, which, on the basis of double staining results,
      were mostly Epstein-Barr virus-infected B cells. A p53 gene mutation was only
      found in 1 case (1/8 cases) of angioimmunoblastic lymphoma, which showed
      cytologic tumor progression. Mycosis fungoides showed p53 overexpression in 2 of
      4 cases, including 1 case with p53 gene mutation and features of cytologic tumor
      progression. Nasal NK/T lymphomas showed p53 overexpression in 2 of 5 cases, 1 of
      which had a p53 gene mutation. Finally, all lymphoblastic T-cell lymphomas (5
      cases) and gammadelta hepatosplenic T-cell lymphomas (3 cases) were negative for
      expression of p53 and p21 proteins. We conclude that p53 protein overexpression
      is a common finding in some entities of T- and T/NK-cell lymphomas, whereas a p53
      gene mutation is a rare, sporadic, and rather late event associated with tumor
      progression in some instances. The p53/p21 expression pattern appears to be
      variable in T- and T/NK-cell lymphoma entities, reinforcing the concept of
      distinct, entity-related mechanisms of pathogenesis in these tumors.

PMID- 11230708
TI  - The clinical and pathologic implications of plasmacytic infiltrates in
      percutaneous renal allograft biopsies.
AB  - Plasmacytic infiltrates in renal allograft biopsies are uncommon and
      morphologically distinctive lesions that may represent variants of acute
      rejection. This study sought significant clinical and pathologic determinants
      that might have influenced development of these lesions and assessed their
      prognostic significance. Renal allograft biopsies (n = 19), from 19 patients,
      with tubulointerstitial inflammatory infiltrates containing abundant plasma
      cells, composing 32 +/- 8% of the infiltrating mononuclear cells, were classified
      using Banff '97 criteria. Clonality of the infiltrates was determined by
      immunoperoxidase staining for kappa and lambda light chains and polymerase chain
      reaction for immunoglobulin heavy-chain gene rearrangements, using V(H) gene
      framework 3 and JH consensus primers. In situ hybridization for Epstein-Barr
      virus encoded RNA (EBER) was performed in 17 cases. The clinical features,
      histology, and outcome of these cases were compared with kidney allograft
      biopsies (n = 17) matched for time posttransplantation and type of rejection by
      Banff '97 criteria, with few plasma cells (7 +/- 5%). Sixteen of 19 biopsies
      (84%) with plasmacytic infiltrates had EBER-negative (in 14 cases tested)
      polyclonal plasma cell infiltrates that were classifiable as acute rejection
      (types 1A [4], 1B [10], and 2A [2]). These biopsies were obtained between 10 and
      112 months posttransplantation. Graft loss from acute and/or chronic rejection
      was 50% at 1 year and 63% at 3 years, and the median time to graft failure was
      4.5 months after biopsy. There was no significant difference in overall survival
      or time to graft failure compared with the controls. Three of 19 biopsies (16%)
      had EBER-negative polyclonal plasmacytic hyperplasia, mixed monoclonal and
      polyclonal polymorphous B cell hyperplasia, and monoclonal plasmacytoma-like
      posttransplantation lymphoproliferative disease (PTLD) and were obtained at 17
      months, 12 weeks, and 7 years after transplantation, respectively. Graft
      nephrectomies were performed at 1, 19, and 5 months after biopsy, respectively.
      Plasmacytic infiltrates in renal allografts comprise a spectrum of lesions from
      acute rejection to PTLD, with a generally poor prognosis for long-term graft
      survival.

PMID- 11230709
TI  - Histologic distribution of fatal rotaviral infection: an immunohistochemical and
      reverse transcriptase in situ polymerase chain reaction analysis.
AB  - Rotaviral infection is the most common cause of gastroenteritis in young
      children. Although rotavirus infection has a high morbidity and mortality rate in
      animals, in most cases in the United States the disease appears to be self
      limited in humans. We report on 2 cases of fatal rotaviral infection in a 1 year
      old and a 4 year old. In each case, the illness showed a rapid systemic course
      dominated by cardiac and central nervous system involvement; in one case,
      rotaviral infection was documented by stool culture. Viral RNA was localized by
      reverse transcriptase in situ polymerase chain reaction to the mucosal cells of
      the small and large intestine and to many other tissues, including the heart and
      central nervous system, where it was noted in the endothelial cells of the
      microvasculature. Immunohistochemical analysis for the virus showed an identical
      histologic distribution in the intestinal epithelial cells and the systemic
      microvasculature. It is concluded that rotaviral infection can lead to a fatal
      disseminated infection in humans and the mechanism of this complication is based
      on a diffuse endothelialitis and concomitant tissue damage.

PMID- 11230710
TI  - Genomic alterations in tubular breast carcinomas.
AB  - Tubular carcinoma of the breast is a well-differentiated variant of invasive
      ductal carcinoma and has been shown to have an exceptionally favorable prognosis,
      as manifested by a low incidence of lymph node metastases and an excellent
      overall survival. It is unknown whether this subtype represents an early step
      along the continuum of development to a more aggressive, poorly differentiated
      ductal cancer, or whether these cancers are destined to remain well
      differentiated with limited metastatic potential. We undertook an analysis of 18
      pure tubular carcinomas of the breast using comparative genomic hybridization to
      evaluate the chromosomal changes in these tumors. An average of 3.6 chromosomal
      alterations of the genome were identified per case. The most frequent change
      involved loss of 16q (in 78% of tumors) and gain of 1q (in 50% of tumors). All
      but one case with 1q gain also exhibited a concomitant 16q loss. Other frequent
      changes involved 16p gain in 7 of 18 cases (39%) and distal 8p loss in 5 of 18
      cases (28%). Comparison with known genomic alterations in a mixed group of
      invasive cancers shows tubular cancer to have fewer overall chromosomal changes
      per tumor (P <.01), higher frequency of 16q loss (P <.001), and lower frequency
      of 17p loss (P =.007). These results strongly suggest that tubular carcinomas are
      a genetically distinct group of breast cancers.

PMID- 11230711
TI  - Cutaneous angiolymphoid hyperplasia with high endothelial venules is
      characterized by endothelial expression of cutaneous lymphocyte antigen.
AB  - Two cases in which the presence of cutaneous lesions with a characteristic
      admixture of lymphoid hyperplasia and vascular proliferation lead to the
      diagnosis of so-called acral pseudolymphomatous angiokeratoma (APA) of children
      are reported. Owing to the prominence of its blood vessels, so striking as to be
      reminiscent of high endothelial venules (HEVs), APA was initially interpreted as
      a vascular lesion rather than a pseudolymphoma. This resemblance is further
      compounded by our finding that cutaneous lymphocyte antigen (CLA), an HEV marker,
      is also expressed in APA epithelioid blood vessels. Consequently, we believe that
      "cutaneous angiolymphoid hyperplasia with high endothelial venules" (ALH-HEV),
      which alludes to the dual nature of proliferating elements and the HEV-like
      phenotype of the vascular component, would be a better denomination for this
      entity. Additionally, we speculate that ALH-HEV lymphoid hyperplasia self
      perpetuates through the transformation of dermal capillaries into HEVs, which
      would bind non-skin homing lymphocytes expressing L-selectin and promote their
      local recruitment and recirculation.

PMID- 11230712
TI  - Transitional cell carcinoma of the endometrium associated with a benign ovarian
      Brenner tumor: a case report.
AB  - Transitional cell carcinomas (TCCs) of the endometrium are rare, and only 10
      cases have been described to date. We report the case of a 46-year-old woman who
      developed both a TCC of the endometrium and a benign ovarian Brenner tumor. Such
      an association has not yet been reported in the literature. Immunohistochemical
      studies of the uterine tumor showed cytokeratin 7 positivity and cytokeratin 20
      negative staining, which was consistent with a Mullerian derivation. Human
      papilloma virus (HPV) immunostaining as well as polymerase chain reaction (PCR)
      analysis using primers for HPV types 6, 11, 16, and 18 failed to detect viral
      DNA. The coexistence of a TCC of the endometrium and an ovarian Brenner tumor
      might be coincidental but raises the possibility of a field effect, as seen with
      multifocal endometrioid tumors or multiple urinary tract TCCs.

PMID- 11230713
TI  - Pigmented renal clear cell carcinoma with melanocytic differentiation.
AB  - Renal cell carcinoma (RCC) is the most common malignant tumor of the adult
      kidney, and its incidence has been steadily rising. RCC consists of several
      subtypes, each of which has its own clinical features, and cytogenetic and
      molecular characteristics. Recognizing histologic patterns of RCC is important
      not only for correct diagnosis, but also for providing insight into the
      biological behavior of the tumor and subsequent appropriate medical care for the
      patient. Pigments other than hemosiderin has been observed in RCC, but none of
      them have been proved to be melanin. Melanotic tumors, either primary or
      metastatic, are rare in the kidney. We present an unusual case of melanin
      pigmented clear cell RCC with melanocytic differentiation, an unusual variant
      that may lead to errors in diagnosis and treatment.

PMID- 11230715
TI  - The (nearly) forgotten calcifications.

PMID- 11230714
TI  - A case of late onset cardiac amyloidosis with a new transthyretin variant (lysine
      92).
AB  - A new transthyretin (TTR) variant (lysine 92), which causes late onset cardiac
      amyloidosis, is described in a 71-year-old man. The patient at first had syncope
      due to ventricular tachycardia and was admitted our hospital. Typical findings of
      cardiac amyloidosis were observed by echocardiography, and a diagnosis of
      systemic amyloidosis was made by rectal biopsy. The man died approximately 3
      years and 6 months after first admission, with gradually worsening congestive
      heart failure. Pathological examination showed prominent amyloid deposits in the
      heart and the vascular wall of many organs including the liver, pancreas, kidney,
      lung, and gastrointestinal tracts. Amyloid protein of transthyretin type was
      indicated by immunohistochemical study, and DNA sequencing identified a novel
      mutation in the transthyretin gene encoding 92 glutamine --> lysine. A polymerase
      chain reaction-induced mutation restriction analysis with a mismatched antisense
      primer showed that the patient was heterozygous for the TTR Lys92 allele.

PMID- 11230717
TI  - Immunostains after glutaraldehyde-based tissue fixation.

PMID- 11230718
TI  - Effects of isoflurane, enflurane, and halothane on skeletal muscle
      microcirculation in the endotoxemic rat.
AB  - PURPOSE: The cardiovascular effects of volatile anesthetics during sepsis sets
      patients at high risk for hemodynamic deterioration. We compared the
      microcirculatory alterations in skeletal muscle under anesthesia with isoflurane,
      enflurane, and halothane in an endotoxemic rat preparation. MATERIALS AND
      METHODS: Twenty-one Sprague-Dawley rats under continuous hemodynamic monitoring
      and intravital microscopy of the spinotrapezius muscle were studied during two
      level lipopolysaccharide (0.2 mg/kg and 2 mg/kg) induced sepsis. The effects of
      equianesthetic concentrations (1.5 minimum alveolar concentration [MAC]) of
      either isoflurane [n:7], enflurane [n:7], or halothane [n:7] on microcirculatory
      vasoregulation were measured and histopathologic changes were evaluated. RESULTS:
      During low-dose endotoxemia, arteriolar vasodilation under isoflurane was nearly
      abolished (P < .05). At high-dose endotoxemia, this lack of vasodilatory effect
      was similar (P < .05). Animals receiving 1.5 MAC of enflurane during low-dose
      endotoxin presented a significant decrease in arteriolar diameter by -11.3 (+/
      2.9%), this response was less during high-dose endotoxemia (-7.0, +/-2.9%).
      Halothane caused pronounced vasoconstriction by -20 (+/-3.7%) during low-dose
      endotoxemia and moderate but significant constriction during high-dose
      endotoxemia (-7.9, +/-2.6%). CONCLUSIONS: Isoflurane, enflurane, and halothane
      exert significantly different effects on vasoregulation of skeletal muscle
      arterioles in the endotoxemic rat.

PMID- 11230719
TI  - Antiarrhythmic effects of adenosine on ischemia-induced ventricular fibrillation.
AB  - PURPOSE: The antiarrhythmic efficacy of adenosine during states of AV-nodal
      reentrant tachycardias is well known and clinically established. Adenosine is
      also able to reduce ventricular arrhythmias when applied before coronary ligation
      in rats. Hypoxia or ischemia leads to an increased production of adenosine by
      cardiac myocytes. The purpose of this study was to evaluate if adenosine also has
      a direct antiarrhythmic effect on ischemia-induced ventricular fibrillation.
      MATERIALS AND METHODS: In this study, the antiarrhythmic effects of adenosine on
      ventricular fibrillation during global (low flow) ischemia were evaluated in
      isolated guinea pig hearts perfused by the method of Langendorff. RESULTS:
      Adenosine showed a dose-dependent prolongation of the peak to peak interval of
      the ventricular ECG signal during ventricular fibrillation until ventricular
      flutter or tachycardia occurred at a concentration of 2 mmol/L. At a
      concentration of 20 mmol/L, adenosine converted ventricular fibrillation into
      ventricular tachycardia with intermittent periods of asystole. This conversion of
      ventricular fibrillation to asystole was antagonised by 200 micromol/L
      theophylline. CONCLUSION: Adenosine appears to have an antiarrhythmogenic effect
      both in supraventricular and ventricular rhythm disturbances. During myocardial
      infarction, where huge amounts of adenosine are present in ischemic regions,
      asystole may respond to adenosine antagonists.

PMID- 11230720
TI  - L-canavanine, a selective inhibitor of inducible NO synthase, increases plasma
      endothelin-1 concentrations in dogs with endotoxic shock.
AB  - PURPOSE: The purpose of this article is to elucidate the effect of L-canavanine,
      a selective inhibitor of inducible NO synthase (iNOS), on hemodynamics, blood gas
      parameters, and plasma concentrations of lactate and endothelin-1 (ET-1) during
      endotoxic shock. MATERIALS AND METHODS: Eleven mongrel dogs under pentobarbital
      anesthesia were divided into two groups: (1) bacterial lipopolysaccharide (LPS)
      plus vehicle group (n = 5) receiving infusion of LPS (3 mg/kg/h for 1 h) followed
      by vehicle (2 mL/h for 5 hours); (2) LPS plus L-canavanine group (n = 6)
      receiving infusion of LPS (3 mg/kg/h for 1 hour) followed by L-canavanine (10
      mg/kg/h for 5 hours). RESULTS: LPS caused a significant (P < .05) decrease in
      mean arterial pressure (MAP) at 1 hour, but there was no significant difference
      in MAP during 6-hour period between the two groups. LPS alone did not cause
      significant changes in other hemodynamics, whereas L-canavanine caused a
      significant (P < .05) increase in pulmonary vascular resistance index (PVRI) and
      a decrease in oxygen delivery at 6 hours. The LPS-induced lactic acidosis and
      hypersecretion of ET-1 were aggravated after L-canavanine infusion. Plasma ET-1
      showed positive correlations to lactate levels and PVRI, and negative
      correlations to cardiac output and oxygen delivery only in the LPS plus L
      canavanine group, but not in the LPS plus vehicle group. CONCLUSIONS: This study
      suggests that L-canavanine induces tissue hypoperfusion and ischemia with
      concomitant hypersecretion of ET-1 in dogs with endotoxic shock.

PMID- 11230721
TI  - Effects of histamine-1 receptor antagonism on leukocyte-independent plasma
      extravasation during endotoxemia.
AB  - PURPOSE: The purpose of this study was to investigate the role of histamine in
      mediating leukocyte-independent microvascular permeability and mast cell
      activation during endotoxemia. Microvascular permeability and mast cell activity
      were determined after inhibition of the L-selectin mediated leukocyte-adherence
      by fucoidin and after inhibition of histamine effects by the histamine H1
      receptor antagonist diphenhydramine. MATERIALS AND METHODS: In male Wistar rats,
      leukocyte rolling, leukocyte adherence, microvascular permeability, and mast cell
      activity were determined in mesenteric postcapillary venules using intravital
      microscopy. After pretreatment with the histamine H1-receptor antagonist
      diphenhydramine, animals in the ETX/H1-ANT group received a continuous infusion
      of endotoxin. Animals in the ETX group underwent the same procedure, but received
      saline 0.9% instead of diphenhydramine. In both groups, leukocyte adherence was
      prevented by administration of fucoidin. Animals in the control group received
      volume-equivalent saline 0.9%. RESULTS: In the endotoxin-challenged groups,
      fucoidin prevented leukocyte rolling and reduced leukocyte adherence to values
      comparable to control group. In the ETX group and the ETX/H1-ANT group both
      microvascular permeability and mast cell activity increased significantly,
      starting at 60 minutes. Differences in mast cell activity between the ETX group
      and the ETX/H1-ANT group were significant at 60 minutes and at 120 minutes.
      Differences in microvascular permeability between the ETX/H1-ANT group and the
      ETX group were not significant. CONCLUSIONS: The leukocyte-independent
      microvascular damage during early endotoxemia cannot be inhibited efficiently by
      the H1-receptor antagonist diphenhydramine, indicating that histamine seems to
      play only a minor role in that pathophysiology. Furthermore, mast cells do not
      seem to be involved in the development of leukocyte-independent plasma
      extravasation during endotoxemia.

PMID- 11230722
TI  - Accuracy of predictions of survival at admission to the intensive care unit.
AB  - PURPOSE: The purpose of this study was to compare the accuracy of outcome
      predictions made on the day of intensive care unit (ICU) admission by critical
      care physicians, critical care fellows, and primary team physicians. PATIENTS AND
      METHODS: Fifty-nine consecutive patients admitted to a Medical-Surgical ICU were
      included in the study. Two ICU attending physicians and two critical care
      fellows, not involved in medical management, evaluated each new ICU patient at
      admission and after 48 to 72 hours. Altogether six ICU attendings and six fellows
      were involved in the study. Each investigator separately assigned probability to
      each patient of being discharged alive from the ICU and the hospital. On the day
      of admission the primary service was also asked to estimate the likelihood of
      successful outcome. All values are expressed in percentiles. Statistical analysis
      was performed by a logistic regression procedure with a binary outcome. Data are
      presented as mean +/- SD. RESULTS: Fifty-nine patients were surveyed. Twenty-six
      (44%) patients died in the ICU, 3 (5%) died in the hospital wards, and 30 (51%)
      were discharged alive from the hospital. ICU attendings most reliably and
      accurately estimated patient outcome on admission compared with critical care
      fellows and primary team physicians. ICU attendings were more consistent than ICU
      fellows at predicting outcome at 48 and 72 hours. Clinical predictions were
      better for patients at the extremes of disease severity, and the accuracy of
      predictions in these patients was highest. Accuracy was diminished in patients
      with moderate compromise of clinical status. CONCLUSION: ICU attendings predicted
      most accurately and consistently the final outcome of patients, and ICU fellows
      estimated outcome more reliably than the primary service. For the most part, the
      primary service tended to overestimate the probability of favorable outcome of
      patients for whom ICU admission had been requested. Additionally, clinical
      accuracy of survival or mortality was best for those patients at the extremes of
      clinical compromise: this point seems to confirm the validity of using clinical
      judgement as a guide to restricting ICU resources for those severely compromised
      or mildly compromised.This study also indicates that predictions of outcome in
      critically ill patients made within days of admission are statistically valid but
      not sufficiently reliable to justify irrevocable clinical decisions at present.

PMID- 11230724
TI  - Activation of alveolar phospholipase A2 after hydrochloric acid aspiration in
      rats.
AB  - PURPOSE: The present study was carried out to determine phospholipase A2 (PLA2)
      activity in the bronchoalveolar lavage fluid (BALF) in rats subjected to HCI
      aspiration. MATERIALS AND METHODS: Rats were allocated into one of five groups.
      Groups H-1 and H-3 received instillation of HCI into lungs. Groups S-1 and S-3
      received saline instead of HCI. Group C received no instillation. BAL was
      performed according to the protocol, that is, 1 hour after the instillation in
      groups H-1 and S-1, 3 hours after the instillation in groups H-3 and S-3, and
      arbitrarily in group C. Obtain BALF was analyzed for the protein concentration,
      PLA2 activity, and the molecular mass of PLA2. RESULTS: The protein concentration
      in BALF showed an increase in groups H-1 and H-3. PLA2 activity decreased in
      group H-1, but increased in group H-3, compared with groups S-1 and S-3,
      respectively. PLA2 in groups C and H-1 revealed a high molecular mass (HM), but
      that in group H-3 revealed a low molecular mass (LM). CONCLUSIONS: There is an
      increase in the alveolar LM-PLA2 at inflammatory phase after HCI aspiration,
      suggesting the pathophysiologic role of LM-PLA2 in the acute lung injury.

PMID- 11230723
TI  - Nutritional deficiencies and blunted erythropoietin response as causes of the
      anemia of critical illness.
AB  - PURPOSE: The purpose of this article was to determine the prevalence of iron,
      vitamin B12, and folate deficiency and to evaluate the erythropoietin (EPO)
      response to anemia in a cohort of long-term intensive care unit (ICU) patients.
      MATERIALS AND METHODS: All patients admitted to three academic medical center
      multidisciplinary ICUs were screened for eligibility into a randomized trial of
      EPO for the treatment of ICU anemia. On their second or third ICU day, patients
      enrolled in this trial had EPO levels drawn and were screened for iron, B12, and
      folate deficiency. Weekly EPO levels were obtained throughout patients' ICU stay.
      RESULTS: A total of 184 patients were screened for iron, B12, and folate
      deficiency. Sixteen patients (9%) were iron deficient by study criteria, 4 (2%)
      were B12 deficient, and 4 (2%) were folate deficient. Mean hemoglobin and
      reticulocyte percents of the remaining 160 patients were 10.3 +/- 1.2 g/dL and
      1.66 +/- 1.09%, respectively. In most patients, serum iron and total iron binding
      capacity levels were very low, whereas ferritin levels were very high. Mean and
      median day 2 EPO levels were 35.2 +/- 35.6 mIU/mL and 22.7 mIU/mL, respectively
      (normal = 4.2-27.8). Serial EPO levels in most persistently anemic patients
      remained within the normal range. CONCLUSIONS: In this cohort, screening for
      iron, B12, and folate deficiency identified potentially correctable abnormalities
      in more than 13% of patients and should be considered in those who are
      anticipated to have long ICU stays. Even at an early point of critical illness,
      most patients had iron studies consistent with anemia of chronic disease (ACD),
      as well as a blunted EPO response that may contribute to this ACD-like anemia of
      critical illness.

PMID- 11230726
TI  - Bad time for Bonzo? Experimental models of hepatitis C virus infection,
      replication, and pathogenesis.

PMID- 11230727
TI  - Bile acid transport and regulating functions in the human biliary epithelium.
AB  - Whether bile acids regulate biliary epithelial cell (BEC) secretory functions in
      human is poorly known. The purpose of the study was to determine if human
      gallbladder-derived BEC exhibit bile acid transport activity that affect their
      secretory functions and to evaluate the influence of bile acid hydrophobicity in
      this response by comparing the effects of tauroursodeoxycholate (TUDC) and of
      taurochenodeoxycholate (TCDC). Expression of the apical sodium-dependent bile
      acid transporter (ASBT) and of the organic anion transporting polypeptide (OATP
      A) was detected and associated with sodium-dependent and sodium-independent
      [(3)H]taurocholate uptake in BEC. Sodium-dependent uptake (K(m), 66 +/- 2.5
      micromol/L; Vmax, 39.4 +/- 4.6 pmol/mg protein/min) was significantly higher than
      sodium-independent uptake. TCDC stimulated Cl(-) efflux and mucin secretion in
      cultured cells, and both effects were sodium-dependent. Both TCDC and TUDC were
      efficiently transported in BEC, as assessed by competitive uptake experiments.
      However, as compared with TCDC, TUDC induced significantly lower mucin secretion
      whereas there was no significant difference between TCDC- and TUDC-induced
      chloride efflux. Protein kinase C down-regulation caused a 70% reduction in TUDC
      induced mucin secretion, but did not affect TCDC-induced secretion, which was
      mediated predominantly by Ca(2+)/calmodulin-dependent protein kinase II
      activation. These results provide evidence that bile acids may be transported
      mainly via ASBT in human gallbladder BEC and stimulate hydroelectrolytic and
      mucin secretion in these cells. Individual bile acids activate different
      signaling pathways leading to a different balance between mucin and chloride
      secretion. The differential effect of TUDC may cause a reduction in bile
      inspissation and provide a benefit in biliary disorders.

PMID- 11230728
TI  - Ursodeoxycholic acid administration in patients with cholestasis of pregnancy:
      effects on primary bile acids in babies and mothers.
AB  - Little is known about the effects on the fetus of ursodeoxycholic acid (UDCA)
      treatment for intrahepatic cholestasis of pregnancy (ICP). Twenty ICP patients
      were given UDCA at 1.5 to 2 g/d, to our knowledge the highest dosage yet
      reported. Effects were evaluated on conjugated bile acids (BA) in amniotic fluid
      (15 of 20 patients) and umbilical cord serum obtained at delivery (20 of 22
      newborns), as compared with 10 untreated patients (amniotic fluid, 9 of 10
      patients; cord serum, 9 of 10 newborns). Liver function tests, serum BA and UDCA
      were evaluated on enrollment and then weekly until 1 week after delivery.
      Maternal serum conjugated cholic (CCA) and chenodeoxycholic (CCDCA) acids levels
      fell (18.5 +/- 1.9 to 10.5 +/- 1.9 micromol/L, and 5.8 +/- 0.8 to 2.97 +/- 0.7
      micromol/L, respectively [P <.01]) in treated patients, and remained unaffected
      (20.0 +/- 3.1 vs. 20.3 +/- 2.3, and 5.6 +/- 0.6 vs. 5.4 +/- 0.5, respectively [P
      = not significant]) in untreated ones. Serum conjugated UDCA levels rose to 16.5
      +/- 1.8 micromol/L (P<.001). Median values of CCA and CCDCA in amniotic fluid
      around delivery were 4.9 +/- 12.4 and 4.8 +/- 7.7 micromol/L, respectively, in
      treated patients, as against 17.9 +/- 27.5 and 18.5 +/- 20.9 micromol/L in
      untreated ones. In treated mothers, CCA and CCDCA concentrations in cord blood
      were 6.0 +/- 0.9 and 5.2 +/- 0.95 micromol/L, respectively, as against 21.9 +/-
      5.6 and 18.9 +/- 2.1 micromol/L in untreated ones. In treated patients, median
      UDCA values in amniotic fluid and cord blood were 0.8 +/- 2.4 and 0.9 +/- 0.14
      micromol/L, respectively. We conclude that increasing the dose of UDCA more
      effectively controls ICP and improves maternal clinical outcome after delivery.

PMID- 11230729
TI  - Regulation of the dynamic localization of the rat Bsep gene-encoded bile salt
      export pump by anisoosmolarity.
AB  - Canalicular transport via the bile salt export pump (Bsep) represents the rate
      controlling step in taurocholate excretion, whose capacity is under osmotic
      control. The short-term effects of anisoosmolarity and Ca(2+)-withdrawal on the
      localization of Bsep and the tight junction proteins Zo-1 and occludin were
      studied in perfused rat liver by immunohistochemistry, confocal microscopy, and
      densitometry. Under normoosmotic conditions, Bsep was found in the canalicular
      membrane and showed a punctate intracellular localization. Hypoosmolarity
      resulted in the translocation of intracellular Bsep to the canalicular membrane,
      whereas hyperosmolarity induced a retrieval of Bsep. Following hyperosmolar
      retrieval of Bsep and multidrug resistance protein 2 (Mrp2) from the canalicular
      membrane, in the putative intracellular vesicles Bsep and Mrp2 colocalized in 15%
      of these vesicles, whereas 85% stained either positive for Bsep (61%) or Mrp2
      (24%). Anisotonicity had no effect on the linear staining patterns of occludin
      and Zo-1, indicating no increase in paracellular permeability. Omission of
      calcium produced cholestasis characterized by a disruption of occludin, whereas
      the localization of Zo-1, Bsep, and Mrp2 remained unaffected. It is concluded (1)
      that hyperosmolarity induces retrieval of Bsep from the canalicular membrane,
      which correlates to cholestasis. Hypoosmolarity leads to choleresis accompanied
      by a rapid recruitment of intracellular Bsep to the canalicular membrane. (2)
      Bsep- and Mrp2-specific vesicles participate in the short-term osmoregulation of
      canalicular secretion, however, a cause-effect relationship between bile salt
      excretion and transporter localization remains to be established. (3) Ca(2+)
      depletion induces cholestasis by disruption of occludin-determined tight
      junctional permeability, whereas internalization of canalicular transporters play
      a minor role.

PMID- 11230730
TI  - Morphogenesis of primary human biliary epithelial cells: induction in high
      density culture or by coculture with autologous human hepatocytes.
AB  - Although the control of biliary ductular morphogenesis has received some
      attention particularly using isolated rat biliary epithelial cell models, the
      regulation of human bile duct formation is not well defined. In the present
      study, using a 3-dimensional culture model comprising primary human biliary
      epithelial cells (BECs) and coculture with primary human hepatocytes, we have
      sought to define the factors involved. We have shown that primary human BECs can
      be expanded on collagen gels in the absence of growth factors or serum. When
      plated in high density in double collagen gels, BECs established 3-dimensional
      structures that subsequently developed into well differentiated polarized luminal
      ducts. This morphogenic response occurred in the absence of hepatocyte growth
      factor (HGF) and epidermal growth factor. Strikingly, the addition of growth
      factors (in the presence of serum) resulted in loss of polarity although the
      cells retained growth responses to both factors. Coculture of BECs with
      autologous human hepatocytes enhanced the ability of low-density BECs to undergo
      ductulogenesis. This effect was mimicked by addition of conditioned medium from
      previous hepatocyte-BEC cocultures. These findings indicate that for human
      biliary ductular morphogenesis, epithelial cell-cell interactions are required
      but that mesenchymally derived factors such as HGF may not be important.

PMID- 11230731
TI  - Molecular identification of bacterial 16S ribosomal RNA gene in liver tissue of
      primary biliary cirrhosis: is Propionibacterium acnes involved in granuloma
      formation?
AB  - The etiopathogenesis of primary biliary cirrhosis (PBC) remains speculative.
      Epithelioid granulomas are often found in the vicinity of damaged interlobular
      bile ducts in PBC, raising the possibility of a reaction to microbial materials.
      In this study, we tried to detect and identify bacterial DNA within granulomatous
      lesions in PBC. Using liver sections from 9 patients with PBC and 13 control
      livers, granuloma in portal tracts, portal tracts without granuloma, and adjacent
      hepatic parenchyma were selectively microdissected from sections, and then DNA
      was extracted from them. First, part of the bacterial 16S ribosomal RNA (rRNA)
      gene was amplified from DNA samples extracted from 5 PBC and 6 control livers,
      and their amplicons were sequenced for the identification of bacterial species.
      Several indigenous bacteria were identified. Among them, Propionibacterium acnes
      (P. acnes) was detected as a major clone in 20% to 50% of sequenced clones from
      granuloma of PBC, but the detection rate of P. acnes was 0% to 20% in those
      cloned from adjacent hepatic parenchyma of PBC. Then, a P. acnes-specific PCR was
      performed using all microdissected samples. Distinct PCR products were identified
      in epithelioid granuloma in all 9 PBC cases. The result that P. acnes DNA is
      present as a major clone in granulomas of PBC, suggest that P. acnes is involved
      in the pathogenesis of granuloma in PBC.

PMID- 11230732
TI  - Pseudocapillarization and associated energy limitation in the aged rat liver.
AB  - Age-related impairment of drug metabolism by the liver is consistent with
      hepatocyte hypoxia, suggestive of the development of a diffusional barrier to
      oxygen supply. Because the effects of aging on the diffusional pathway
      (sinusoidal endothelium and space of Disse) have not been described, we performed
      comparative studies on the livers of Fischer F344 rats aged 4 to 7, 12 to 15, and
      24 to 27 months. Light-microscopic examination revealed no evidence of fibrosis,
      cirrhosis, or other specific pathology. In contrast, scanning and transmission
      electron-microscopic examination revealed that aging is associated with
      pseudocapillarization of the sinusoidal endothelium, indicated by defenestration
      with reduced porosity, thickening of the endothelium, infrequent development of
      basal lamina, and only minor collagen deposits in the space of Disse.
      Furthermore, immunohistochemistry studies showed strong expression of collagen
      IV, moderate expression of factor VIII-related antigen, and weak expression of
      collagen I along the sinusoids of livers from old rats (P <.0001). In vitro (31)P
      magnetic resonance spectroscopy analysis showed that aging is associated with
      changes in high-energy phosphate and other metabolites, consistent with
      hepatocyte hypoxia. Aging in the liver is associated with changes in the
      sinusoidal endothelium and space of Disse that may restrict the availability of
      oxygen and other substrates.

PMID- 11230733
TI  - Autoimmune hepatitis/sclerosing cholangitis overlap syndrome in childhood: a 16
      year prospective study.
AB  - To investigate whether sclerosing cholangitis with an autoimmune serology
      characteristic of autoimmune hepatitis (AIH) and AIH are distinct entities, we
      studied 55 consecutive children with clinical and/or biochemical evidence of
      liver disease and circulating antinuclear (ANA), anti-smooth muscle (SMA), and/or
      liver-kidney-microsomal type 1 (LKM1) autoantibodies. They underwent liver
      biopsy, direct cholangiography, sigmoidoscopy, and rectal biopsy at presentation.
      Twenty-eight were diagnosed as AIH in the absence and 27 autoimmune sclerosing
      cholangitis (ASC) in the presence of radiological features of cholangiopathy.
      Twenty-six ASC and 20 AIH had ANA and/or SMA; 1 ASC and 8 AIH LKM1 autoantibody.
      Similarities between the 2 conditions included most clinical and biochemical
      parameters and a lower frequency of HLA DR4. Inflammatory bowel disease and
      histological biliary changes were more common in ASC; coagulopathy,
      hypoalbuminemia, lymphocytic periportal hepatitis, and HLA DR3 were more common
      in AIH. Histological biliary changes were observed in 65% of ASC and 31% of AIH
      patients. Eighty-nine percent responded to immunosuppression. Follow-up liver
      biopsies from 17 ASC and 18 AIH patients had similarly reduced inflammatory
      activity and no progression to cirrhosis. Sixteen follow-up cholangiograms from
      AIH patients and 9 from ASC patients were unchanged, while 8 ASC patients showed
      a progressive cholangiopathy. One child with AIH and ulcerative colitis developed
      sclerosing cholangitis 8 years after presentation. At 2 to 16 years (median, 7
      years) from presentation, all patients are alive, including 4 ASC patients who
      underwent liver transplantation. In conclusion, ASC and AIH are similarly
      prevalent in childhood; cholangiography is often needed to distinguish between
      these 2 entities, which are likely to lie within the same disease process.

PMID- 11230734
TI  - Collagen type Ialpha1 and vitamin D receptor gene polymorphisms and bone mass in
      primary biliary cirrhosis.
AB  - The potential influence of two gene polymorphisms, vitamin D receptor gene (VDR)
      and the gene encoding collagen type Ialpha1 (COLIA1) Sp1 polymorphisms, in the
      reduced bone mass observed in patients with primary biliary cirrhosis (PBC) was
      assessed in 61 women with PBC (age, 54.1 +/- 1.1 years) by restriction enzyme
      digestion of polymerase chain reaction (PCR)-amplified DNA extracted from whole
      blood. Bone mineral density (BMD) of the lumbar spine (L2-L4) and proximal femur
      were measured by X-ray absorptiometry. The severity of liver disease and
      cholestasis was also evaluated, and changes in BMD were calculated after a mean
      period of 2.9 +/- 0.3 years in 41 patients. Sixteen patients (26 %) had the BB,
      20 the bb (33 %), and 25 Bb (41%) VDR genotypes. There were no significant
      baseline BMD differences among the 3 VDR genotypes. Forty-one patients (68%) had
      the SS, 16 the Ss (27%), and 3 the ss (5%) COLIA1 genotypes. The baseline lumbar
      BMD was significantly lower in patients having the s allele than in the
      homozygote SS patients (Z-score, -0.76 +/- 0.24 vs. -0.10 +/- 0.17, P =.02). The
      severity of cholestasis was not related to the VDR or COLIA1 1 polymorphisms.
      Lumbar bone loss was independent of VDR and COLIA1 genotypes, but it was
      associated with cholestasis. In conclusion, the COLIA1 but not VDR polymorphism
      is a genetic marker of peak bone mass in patients with PBC, although the severity
      of cholestasis is the main factor for osteoporosis since it is associated with
      the rate of bone loss.

PMID- 11230735
TI  - Expression of mRNA for DNA methyltransferases and methyl-CpG-binding proteins and
      DNA methylation status on CpG islands and pericentromeric satellite regions
      during human hepatocarcinogenesis.
AB  - To evaluate the significance of alterations in DNA methylation during human
      hepatocarcinogenesis, we examined levels of mRNA for DNA methyltransferases and
      methyl-CpG-binding proteins and the DNA methylation status in 67 hepatocellular
      carcinomas (HCCs). The average level of mRNA for DNMT1 and DNMT3a was
      significantly higher in noncancerous liver tissues showing chronic hepatitis or
      cirrhosis than in histologically normal liver tissues, and was even higher in
      HCCs. Significant overexpression of DNMT3b and reduced expression of DNMT2 were
      observed in HCCs compared with the corresponding noncancerous liver tissues. DNA
      hypermethylation on CpG islands of the p16 (8% and 66%) and hMLH1 (0% and 0%)
      genes and methylated in tumor (MINT) 1 (6% and 34%), 2 (24% and 58%), 12 (21% and
      33%), 25 (0% and 5%), and 31 (0% and 23%) clones, and DNA hypomethylation on
      satellites 2 and 3 (18% and 67%), were detected in noncancerous liver tissues and
      HCCs, respectively. There was no significant correlation between the expression
      level of any DNA methyltransferase and DNA methylation status. Reduced expression
      of DNA repair protein, MBD4, was significantly correlated with poorer tumor
      differentiation and involvement of portal vein. Slightly reduced expression of
      MBD2 was detected in HCCs, and the expression of MeCP2 was particularly reduced
      in HCCs with portal vein involvement. These data suggest that overexpression of
      DNMT1 and DNMT3a, DNA hypermethylation on CpG islands, and DNA hypomethylation on
      pericentromeric satellite regions are early events during hepatocarcinogenesis,
      and that reduced expression of MBD4 may play a role in malignant progression of
      HCC.

PMID- 11230736
TI  - Mechanism of retarded liver regeneration in plasminogen activator-deficient mice:
      impaired activation of hepatocyte growth factor after Fas-mediated massive
      hepatic apoptosis.
AB  - Urokinase-type plasminogen activator (uPA) is implicated in the regulation of
      hepatic regeneration by activating hepatocyte growth factor (HGF). Here, we
      investigated its role in the hepatic regeneration after Fas-mediated massive
      hepatocyte death employing mice deficient in either uPA or its inhibitor,
      plasminogen activator inhibitor-1 (PAI-1). We measured kinetics of hepatic levels
      of proliferating cell nuclear antigen (PCNA)-labeling index, plasmin activity,
      mature HGF, and its phosphorylated receptor, c-Met. In the genetically targeted
      and wild-type mice, hepatocytes fell into the same extent of apoptosis 6 to 12
      hours after an intraperitoneal injection with anti-Fas antibody, as judged from
      histologic analysis and a histon-DNA enzyme-linked immunosorbent assay (ELISA).
      In the wild-type mice, mature HGF emerged in the liver 6 hours following anti-Fas
      injection, and hepatic PCNA-labeling index started to increase following 24 hours
      and peaked at 48 hours. In the uPA(-/-) mice, emergence of mature HGF was delayed
      12 hours and hepatic regeneration peaked at 96 hours. Supplementation with the
      uPA gene to the uPA(-/-) mice by in vivo lipofection restored hepatic plasmin
      levels, and improved a delay in the expression of both mature HGF and
      phosphorylated c-Met, accompanying a normal rate of liver regeneration. In
      contrast, PAI-1(-/-) mice showed accelerated liver regeneration; mature HGF
      emerged as early as 3 hours, and PCNA-labeling index increased at 24 hours. This
      accelerated regeneration was abolished by administration with anti-HGF antibody.
      These results strongly suggest a physiologic role of uPA in the proteolytic
      maturation of HGF, and thereby in hepatic regeneration after Fas-mediated massive
      hepatocyte death.

PMID- 11230737
TI  - Inhibition of intrahepatic metastasis of human hepatocellular carcinoma by Rho
      associated protein kinase inhibitor Y-27632.
AB  - Intrahepatic metastasis is one of the most important prognostic factors for
      patients with hepatocellular carcinoma (HCC). Cell motility mediated by Rho- and
      p160 Rho-associated coiledcoil forming protein kinase (p160ROCK) signaling
      pathways has recently been shown to play a critical role in intrahepatic
      metastasis in human HCC. Furthermore, the stable introduction of dominant
      negative p160ROCK into Li7 cells resulted in a reduced metastatic rate in mice
      with severe combined immunodeficiency (SCID). To investigate whether the specific
      p160ROCK inhibitor, Y-27632, could also inhibit intrahepatic metastasis, the
      effect of Y-27632 on the cell motility and intrahepatic metastasis of Li7 was
      investigated. Y-27632 markedly blocked actin reorganization and motility of Li7
      cells mediated by lysophosphatidic acid (LPA). Y-27632 was administered
      continuously into the peritoneal cavity using a micro-osmotic pump, together with
      orthotopic implantation of Li7 cells into the liver of SCID mice. Phosphate
      buffered saline (PBS) alone was administered as the control. The incidence of
      mice with metastatic nodules decreased in the Y-27632-treated group. The primary
      tumor volume at the site of injection was smaller in the Y-27632-treated group
      compared with the control group, but the difference was not statistically
      significant. Histologically, control tumors showed infiltrative growth into the
      sinusoidal area at the tumor boundary, whereas Y-27632-treated tumors showed
      expansive growth and low invasiveness. These findings confirm the importance of
      the Rho/p160ROCK signaling pathway in intrahepatic metastasis of human HCC, and
      indicate that Y-27632 may be useful for the prevention of intrahepatic metastasis
      of human HCC.

PMID- 11230738
TI  - Bile acids induce eosinophil degranulation by two different mechanisms.
AB  - Eosinophil infiltration and activation occur in the vicinity of the bile ducts in
      immune cholangiopathies. When cholangiocytes are injured, bile acids may cross
      the damaged biliary epithelia and affect periductal immune cells. Although
      immunomodulatory actions of bile acids have been well explored, their effects on
      eosinophils have never been examined. In this study, we tested the hypothesis
      that bile acids directly activate eosinophils and induce their effector
      functions. We found that a hydrophobic bile acid, taurine-con- jugated
      chenodeoxycholic acid (TCDCA), induces eosinophil degranulation in vitro via 2
      different mechanisms depending on its concentration. Degranulation induced by 100
      to 500 micromol/L TCDCA was an active and regulated release because it was
      completely abolished by a tyrosine kinase inhibitor (genistein), by a
      microfilament inhibitor (cytochalasin B), and by incubation at 4 degrees C.
      Furthermore, eosinophils stimulated with 10 to 250 micromol/L TCDCA vigorously
      produced superoxide and interleukin-8 (IL-8). In contrast, at higher
      concentrations (e.g., > or = 1,000 micromol/L), TCDCA induced granule protein
      release without concomitant superoxide production and IL-8 production. Further
      genistein and cytochalasin B failed to inhibit eosinophil degranulation induced
      by 2,500 micromol/L TCDCA, suggesting that TCDCA at this concentration induced
      passive degranulation via cytolysis. The analyses of cell morphology and
      functional viability also supported the presence of 2 mechanisms for TCDCA
      induced eosinophil degranulation. Taurine-conjugated ursodeoxycholic acid, a
      hydrophilic bile acid, similarly activated human eosinophils at relatively low
      concentrations, although the potency was always lower compared with that of
      TCDCA. In conclusion, we have shown that bile acids are capable of directly
      activating eosinophils.

PMID- 11230739
TI  - Soluble liver antigen: isolation of a 35-kd recombinant protein (SLA-p35)
      specifically recognizing sera from patients with autoimmune hepatitis.
AB  - Autoantibodies to soluble liver antigen (SLA) are considered a specific marker of
      autoimmune hepatitis. We have performed immunoscreening of a human liver gene
      expression library with an anti-SLA-positive serum. A reactive clone with a 35-kd
      open reading frame (ORF) and a 563 base pair (bp) 3' untranslated region (UTR)
      was isolated (soluble liver antigen [SLA]-p35), showing strong homology to an
      independently isolated putative SLA/liver-pancreas antigen (LP) sequence (Acc.
      No. AF146396), and a UGA serine tRNA-protein complex (tRNP)((Ser) Sec) related
      protein (AJ238617), as well as different expression sequence tag (EST)-clones
      from lymphatic and oncofetal tissues. Expressed in Escherichia coli, SLA-p35
      showed dose-dependent and complete blocking of reactivity to native SLA antigen
      after preabsorption with the 35-kd recombinant protein. It recognized 67/85
      (78.8%) precharacterized anti-SLA-positive sera in dilutions up to 1:40,000 in
      immunoblot, without detectable cross reactivity in the controls. The commercially
      available SLA/LP enzymelinked immunosorbent assay (ELISA), by comparison,
      recognized 63/85 samples (74.1%). Of the negative samples, 18% showed strong
      inhibition rates (80% and above) in the polyclonal inhibition ELISA. We conlude
      that the complementary DNA now isolated by 3 independent approaches encodes for
      the major but not sole antigenic component of soluble liver antigen. Although its
      truncated form presented here may serve to improve diagnostics based on the new
      recombinant polypeptide, it currently cannot fully replace the polyclonal
      inhibition ELISA.

PMID- 11230740
TI  - Rat hepatic stellate cells contribute to the acute-phase response with increased
      expression of alpha1(I) and alpha1(IV) collagens, tissue inhibitor of
      metalloproteinase-1, and matrix-metalloproteinase-2 messenger RNAs.
AB  - The acute-phase response (APR) represents a systemic reaction of the organism to
      multiple nonspecific inflammatory stimuli. In general, it is protective for the
      host, and hepatocytes are the main cells responding with alterations in the
      expression of a set of liver-specific proteins named the acute-phase proteins. We
      have previously shown that although a turpentine-induced APR is not fibrogenic
      per se, it enhances collagen deposition in rats treated with CCl(4) and up
      regulates expression of hepatic alpha1(I) collagen and tissue inhibitor of
      metalloproteinases 1 (TIMP-1) messenger RNAs (mRNAs). In this report we extended
      our studies and showed that turpentine induced, in a time-dependent manner,
      expression of alpha1(I) and alpha1(IV) collagens, TIMP-1, and matrix
      metalloproteinase 2 (MMP-2) mRNAs. We further showed that expression of these
      mRNAs occurs in hepatic stellate cells, but not in hepatocytes obtained 6 hours
      after the induction of an APR episode. These changes were accompanied by
      increased blood levels of tumor necrosis factor alpha (TNF-alpha) and interleukin
      6 (IL-6) without noticeable immediate changes in the expression of their
      respective mRNAs in the liver. In contrast to CCl(4)-induced liver damage,
      turpentine alone, whether administered as a single dose or as a weekly dose for 3
      weeks did not up-regulate expression of transforming growth factor beta1 (TGF
      beta1) mRNA and did not result in excess collagen deposition. Overall, these
      findings suggest that collagen deposition in the livers of rats with repeated APR
      episodes may be enhanced only when given together with a fibrogenic stimulus that
      activates hepatic stellate cells (HSCs) and/or up-regulates TGF-beta1 mRNA
      expression.

PMID- 11230741
TI  - Phosphoinositide 3-kinase, but not mitogen-activated protein kinase, pathway is
      involved in hepatocyte growth factor-mediated protection against bile acid
      induced apoptosis in cultured rat hepatocytes.
AB  - We have previously shown that cAMP protects against hydrophobic bile acid-induced
      apoptosis in cultured rat hepatocytes through pathways dependent on activation of
      phosphoinositide 3-kinase and inhibition of mitogen activated protein kinase.
      Hepatocyte growth factor protects epithelial cells against apoptosis and
      activates both of these kinases in hepatocytes. We studied the effect of
      hepatocyte growth factor on glycochenodeoxycholate-induced apoptosis to determine
      whether hepatocyte growth factor protects hepatocytes against bile acid-induced
      apoptosis and whether the protective effect is mediated via phosphoinositide 3
      kinase and/or mitogen-activated protein kinase pathways. Two-hour exposure of
      cultured rat hepatocytes to glycochenodeoxycholate resulted in apoptosis in 12.5
      +/- 0.49% of the cells. Pretreatment with hepatocyte growth factor (50 ng/mL)
      decreased apoptosis by 50% to 70%. Hepatocyte growth factor cytoprotection was
      prevented by pretreatment with the phosphoinositide 3-kinase inhibitors,
      wortmannin (50 nmol/L) or Ly 294002 (40 micromol/L). Hepatocyte growth factor
      activated phosphoinositide 3-kinase dependent protein kinase B and mitogen
      activated protein kinase. Pretreatment of hepatocytes with a mitogen-activated
      protein kinase inhibitor, U0126 (40 micromol/L) or an inhibitor of pp70(s6)
      kinase, rapamycin (100 nmol/L), had no effect on the growth factor's anti
      apopotic effect. Treatment with hepatocyte growth factor resulted in mitogen
      activated protein kinase-dependent phosphorylation of BAD on serine(112). In
      summary, hepatocyte growth factor protection against bile acid-induced apoptosis
      occurs via a phosphoinositide 3-kinase pathway and is not dependent on the
      mitogen-activated protein kinase pathway, phosphorylation of BAD on serine(112),
      or activation of p70(S6) kinase.

PMID- 11230742
TI  - Bile acid-induced rat hepatocyte apoptosis is inhibited by antioxidants and
      blockers of the mitochondrial permeability transition.
AB  - The accumulation of hydrophobic bile acids plays a role in the induction of
      apoptosis and necrosis of hepatocytes during cholestasis. The aim of this study
      was to determine in freshly isolated rat hepatocytes the roles of oxidant stress
      and the mitochondrial permeability transition (MPT) in bile acid-induced
      apoptosis. Hepatocytes isolated from adult male Sprague-Dawley rats were
      incubated for 4 hours in buffer containing the hydrophobic bile acid,
      glycochenodeoxycholic acid (GCDC, 0-500 micromol/L) or the hydrophilic bile acid,
      glycocholic acid (GCA), and either the antioxidants, alpha tocopherol, ebselen,
      or idebenone (a coenzyme Q analogue); or the MPT blockers, cyclosporin A, or
      bongkrekic acid, or a caspase-8 inhibitor. Apoptosis was assessed hourly by
      nuclear morphologic changes of fixed cells by DAPI fluorescence microscopy and
      reactive oxygen species (ROS) generation by dichlorofluorescein fluorescence of
      hepatocytes. The percent of cells undergoing apoptosis increased in a time- and
      concentration-dependent manner in cells exposed to GCDC, and to a much lesser
      extent to GCA. ROS generation preceded the onset of apoptosis. MPT blockers,
      caspase-8 inhibition, and antioxidants prevented apoptosis and reduced ROS
      generation by hepatocytes. Flow cytometry analysis showed that MPT occurred
      within 1 hour of exposure of cells to 100 micromol/L GCDC, prior to onset of
      significant apoptosis. In conclusion, ROS generation, MPT induction, and
      cytochrome c release are critical steps in the induction of apoptosis by bile
      acids. Antioxidants may reduce liver injury caused by low levels of bile acids by
      preventing the generation of oxidant stress and subsequent stimulation of the MPT
      and release of cytochrome c from mitochondria.

PMID- 11230743
TI  - Hepatic uptake of organic anions affects the plasma bilirubin level in subjects
      with Gilbert's syndrome mutations in UGT1A1.
AB  - Although in Gilbert's syndrome (GS), bilirubin glucuronidation is impaired due to
      an extra TA in the TATA box of the promoter of the gene for bilirubin UDP
      glucuronosyltransferase 1 (UGT1A1), many GS homozygotes lack unconjugated
      hyperbilirubinemia. Accordingly, an additional defect in bilirubin transport
      might be required for phenotypic expression. Plasma bilirubin and the early
      fractional hepatic uptake rate (BSP K(1)) of a low dose of
      tetrabromosulfophthalein (0.59 micromol/kg) were determined in (1) 15 unrelated
      patients with unconjugated hyperbilirubinemia plus 12 random controls; (2) 4
      unrelated GS probands and 15 of their first-degree relatives; (3) 7 unrelated
      patients with hemolysis due to beta-Thalassemia minor. Subjects were classified
      by DNA sequencing of the promoter region of both UGT1A1 alleles. In group 1, GS
      homozygotes showed a highly significant negative linear correlation between
      plasma bilirubin levels and BSP K(1). BSP K(1) values overlapped considerably
      between GS and normal subjects, whereas, in group 2, they were clustered within,
      and sharply segregated among, families. Patients with hemolysis, despite elevated
      plasma bilirubin levels, had mean BSP K(1) values similar to the normal subjects.
      Within each GS subgroup with defined UGT1A1 mutations, the plasma bilirubin level
      is in part determined by the organic anion uptake rate, assessed by early plasma
      disappearance of low-dose BSP. The lower BSP uptake in GS is not secondary to the
      hyperbilirubinemia, but probably caused by (an) independent, genetically
      determined defect(s) in hepatic transport mechanism(s), shared by BSP and
      bilirubin, that are likely necessary for phenotypic expression of GS.

PMID- 11230744
TI  - Hepatobiliary transporter expression in percutaneous liver biopsies of patients
      with cholestatic liver diseases.
AB  - Reduced hepatobiliary transporter expression could explain impaired hepatic
      uptake and excretion of bile salts and other biliary constituents resulting in
      cholestasis and jaundice. Because little is known about alterations of
      hepatobiliary transport systems in human cholestatic liver diseases, it was the
      aim of this study to investigate such potential changes. Hepatic mRNA levels in
      hepatobiliary transport systems for bile salts (NTCP, BSEP), organic anions
      (OATP2, MRP2, MRP3), organic cations (MDR1), phospholipids (MDR3), and
      aminophospholipids (FIC1) were determined in 37 human liver biopsies and control
      livers by competitive reverse-transcription polymerase chain reaction (RT-PCR).
      Transporter tissue distribution was investigated by immunofluorescence
      microscopy. In patients with inflammation-induced icteric cholestasis (mainly
      cholestatic alcoholic hepatitis), mRNA levels of NTCP, OATP2, and BSEP were
      reduced by 41% (P <.001), 49% (P <.005), and 34% (P <.05) compared with controls,
      respectively. In addition, NTCP and BSEP immunostaining was reduced. MRP2 mRNA
      levels remained unchanged, but canalicular immunolabeling for MRP2 was also
      decreased. mRNA expression of MRP3, MDR1, MDR3, and FIC1 remained unchanged. In
      contrast to the alterations of transporter expression in inflammation-induced
      icteric cholestasis, transporter expression did not change in anicteric
      cholestasis caused by primary biliary cirrhosis (PBC) stages I and II. In
      conclusion, reduced expression of hepatobiliary transport systems for bile salts
      and other organic anions may contribute to inflammation-induced cholestasis in
      humans. Reduction of transporter gene expression can occur at the mRNA level as
      observed for NTCP, OATP2, and BSEP. However, reduced MRP2 immunostaining in the
      presence of conserved MRP2 mRNA levels suggests an additional role for
      posttranscriptional/posttranslational mechanisms.

PMID- 11230745
TI  - Increased cancer risk in a cohort of 230 patients with hereditary hemochromatosis
      in comparison to matched control patients with non-iron-related chronic liver
      disease.
AB  - It has been suggested that excess iron may facilitate the occurrence of cancer.
      Patients with hereditary hemochromatosis (HH) are at high risk of developing
      liver cancer, and studies of limited series reported a high frequency of
      nonhepatic cancers. To verify whether patients with HH are at higher risk of
      liver cancer and other malignancies as compared with patients with non-iron
      related chronic liver disease (CLD), we analyzed the occurrence of neoplasms in
      230 patients with HH and 230 with non-iron-related CLD. The patients were matched
      by sex, age, duration of follow-up (+/-5 years), and severity of liver disease.
      On enrollment, the following variables were considered: hepatitis B virus (HBV)
      and hepatitis C virus (HCV) infections, alcohol abuse, smoking, and a family
      history of cancer (first-degree relatives). The diagnosis of primary cancers was
      confirmed by histology. During the follow-up, hepatocellular carcinoma (HCC)
      developed in 49 and 29 patients (all cirrhotic patients) with HH and non-iron
      related CLD, respectively, with a relative risk of 1.8 (95% confidence interval
      [CI] 1.1-2.9); nonhepatic cancers occurred in 20 and 11 patients, respectively,
      with a relative risk of 1.8 (95% CI 0.8-4). Four patients with HH and 1 with non
      iron-related CLD developed 2 different primary cancers during follow-up. The risk
      of cancer after adjustment for alcohol abuse, smoking, and family history of
      cancer was 1.9 (95% CI 1.1-3.1) in the patients with HH. In conclusion, patients
      with HH are at high risk of both liver cancer and other malignancies, which
      should be carefully sought during follow-up.

PMID- 11230746
TI  - Induction of catalase, alpha, and microsomal glutathione S-transferase in CYP2E1
      overexpressing HepG2 cells and protection against short-term oxidative stress.
AB  - Induction of cytochrome P450 2E1 (CYP2E1) and the formation of reactive oxygen
      species (ROS) appear to be one of the mechanisms by which ethanol is hepatotoxic.
      Glutathione peroxidase and catalase detoxify H(2)O(2). Glutathione S-transferases
      (GST) provide protection from membrane lipid peroxidation, have GSH peroxidase
      activity, and reduce lipid hydroperoxides. Previous studies showed an up
      regulation of GSH synthesis in CYP2E1 expressing HepG2 cells; this finding
      prompted an evaluation of the levels of other antioxidant exzymes. In CYP2E1
      expressing cells, the alpha and microsomal GST messenger RNA (mRNA) are increased
      by 4- and 2-fold, respectively, and catalase protein and mRNA is increased by 2
      fold. The increase in alpha and microsomal GST mRNA correlates with increased
      total enzymatic activity and is caused by increased transcription as evidenced by
      run-on transcription assays. In HepG2 cells transfected to express a different
      cytochrome P450, CYP3A4, there was an increase in alpha GST. However, in contrast
      to the CYP2E1 expressing cells, neither microsomal GST nor catalase were induced,
      suggesting some specificity for CYP2E1. In agreement with an increased
      antioxidant defense system, the sensitivity to added prooxidants such as
      menadione, antimycin A, H(2)O(2), and 4-hydroxynonenal was lower in the CYP2E1
      expressing cells as compared with control cells. In conclusion, overexpression of
      CYP2E1 in HepG2 cells, besides elevating total GSH levels, also induces
      expression of catalase and alpha and microsomal GST. This induction confers
      resistance to the cells against several prooxidants and is suggested to reflect
      an adaptive response by the cells against CYP2E1-mediated oxidative stress.

PMID- 11230747
TI  - Immunolocalization of a novel cholesteryl ester hydrolase in the endoplasmic
      reticulum of murine and human hepatocytes.
AB  - We have recently purified a cholesteryl ester hydrolase (CEH) from rat liver
      microsomes. Antibodies raised against the purified protein specifically reacted
      with a 106-kd protein and neutralized 90% of the CEH activity of rat liver
      microsomes (J Lipid Res 1999;40:715-725). In this work we have used the anti-CEH
      antibody to study both the subcellular distribution of the protein in hepatocytes
      as well as its tissue-specific expression in rat. Western blotting of subcellular
      fractions obtained from isolated rat hepatocytes revealed that the immunoreactive
      106-kd CEH was exclusively localized in microsomes. The antibody also recognized
      a 106-kd protein in microsomes from mouse and human liver but not from rat
      nonparenchymal liver cells. Confocal microscopy of HepG2 cells revealed that CEH
      immunoreactive material colocalized with calnexin, a marker of the endoplasmic
      reticulum. Furthermore, high-resolution immunoelectron microscopy of rat liver
      thin sections exclusively localized the CEH immunoreactivity to the endoplasmic
      reticulum of the hepatocyte. No CEH immunoreactivity was observed in microsomes
      derived from adrenal glands, ovaries, testis, pancreas, intestine, white adipose
      tissue, mammary gland, lung, spleen, brain, aorta, and macrophages. We report a
      CEH localized to the endoplasmic reticulum, erCEH, in the mammalian hepatocyte.
      The subcellular localization and tissue-restricted pattern of expression of erCEH
      suggests that it might have unique functions in liver cholesterol metabolism.

PMID- 11230748
TI  - Cytochrome P450 regulation by hepatocyte nuclear factor 4 in human hepatocytes: a
      study using adenovirus-mediated antisense targeting.
AB  - Hepatocyte nuclear factor 4 (HNF4) is a member of the nuclear receptor super
      family that has shown activating effects on particular cytochrome P450 (CYP)
      promoters from several species. However, its role in the regulation of human CYPs
      in the liver is still poorly understood, as no comprehensive studies in human
      relevant models have been performed. In the present study, we have investigated
      whether HNF4 plays a general role in the expression of 7 major CYP genes in
      primary cultured human hepatocytes. To this end, we developed an adenoviral
      vector for efficient expression of HNF4 antisense RNA. Transduction of human
      hepatocytes with the recombinant adenovirus resulted in a time-dependent increase
      in the antisense transcript, followed by a concomitant decrease in apolipoprotein
      C III mRNA (a target gene of HNF4). Specificity was confirmed by showing that
      increasing levels of HNF4 antisense RNA resulted in the reduction of HNF4
      protein, whereas retinoic X receptoralpha-(RXRalpha), the closest homologous
      member of the nuclear receptor super-family, was unaffected. Analysis of CYP gene
      expression in human hepatocytes transfected with HNF4 antisense RNA revealed
      singular behaviors: (1) CYP3A4, CYP3A5, and CYP2A6 showed an important, dose
      dependent down-regulation on blockage of HNF4 translation; (2) a moderate
      inhibition of CYP2B6, CYP2C9, and CYP2D6 expression was observed (40%-45%
      reduction); (3) the levels of CYP2E1 were not affected even in the absence of
      this transcription factor. In conclusion, using an original strategy (efficient
      antisense RNA expression vector), our study shows that HNF4 is a general
      regulator supporting the expression of major drug-metabolizing CYPs in human
      hepatocytes.

PMID- 11230749
TI  - alpha-fetoprotein-producing hepatoma cell lines share common expression profiles
      of genes in various categories demonstrated by cDNA microarray analysis.
AB  - Liver carcinogenesis is a multistep process involving various genetic
      alterations. cDNA microarray containing 1,080 elements (930 unique genes) was
      used to comprehensively analyze the genetic alterations in hepatoma cell lines,
      and clustering analysis was used to analyze the relatedness of the gene
      expression profiles. Among 7 hepatoma cell lines analyzed, 5-alpha-fetoprotein
      (AFP)-producing hepatoma cell lines (HepG2, Huh7, Hep3B, PLC/PRF/5, and Huh6)
      were shown to have common gene-expression profiles compared with those of AFP
      negative hepatoma cell lines (HLE and SK-Hep1) and cancer cell lines of
      nonhepatocyte origin (HeLa and KMBC). Furthermore, HepG2, Huh7, and Hep3B had
      higher expressions of AFP and shared a common gene-expression profile even when
      compared with other AFP-producing cells. Analysis of the genes with a common
      expression profile among these 3 AFP-positive cells revealed 254 genes across
      various categories. We found that 18 of these genes consistently showed altered
      levels of expression (more than 3-fold changes) in the 3 AFP-producing hepatoma
      cell lines (11 up-regulated and 7 down-regulated). In these 18 genes, 5 genes,
      including that for AFP, were previously reported to be involved in HCC and 6
      genes involved only in other types of cancer. Our study showed that AFP-producing
      hepatoma cell lines shared a distinct expression profile of genes in various
      categories. An understanding of a causal relationship of this particular
      expression profile of genes to AFP-positive and AFP-negative hepatocellular
      carcinoma (HCC) may contribute to more rational therapy in future.

PMID- 11230750
TI  - Mimotopes of the hepatitis C virus hypervariable region 1, but not the natural
      sequences, induce cross-reactive antibody response by genetic immunization.
AB  - The hypervariable region 1 (HVR1) of the putative envelope protein E2 of
      hepatitis C virus (HCV) contains a principal neutralization epitope, and anti
      HVR1 antibodies have been shown to possess protective activity in ex vivo
      neutralization experiments. However, the high rate of variability of this
      antigenic fragment may play a major role in the mechanism of escape from host
      immune response and might represent a major obstacle to developing an HCV
      vaccine. Thus, even if direct experimental evidence of the neutralizing potential
      of anti-HVR1 antibodies by active immunization is still missing, the generation
      of a vaccine candidate with a cross-reactive potential would be highly desirable.
      To overcome the problem of HVR1 variability, we have engineered cross-reactive
      HVR1 peptide mimics (mimotopes) at the N terminus of the E2 ectodomain in plasmid
      vectors suitable for genetic immunization. High levels of secreted and
      biologically active mimotope/E2 chimeras were obtained by transient transfection
      of these plasmids in cultured cells. All plasmids elicited anti-HVR1 antibodies
      in mice and rabbits with some of them leading to a cross-reacting response
      against many HVR1 variants from natural isolates. Epitope mapping revealed a
      pattern of reactivity similar to that induced by HCV infection. In contrast,
      plasmids encoding naturally occurring HVR1 sequences displayed either on full
      length E2 in the context of the whole HCV structural region, or on a soluble,
      secreted E2 ectodomain, did not induce a cross-reacting anti-HVR1 response.

PMID- 11230751
TI  - Combination of interferon and ribavirin in chronic hepatitis C: re-treatment of
      nonresponders to interferon.
AB  - Chronic infection with hepatitis C virus (HCV) may result in cirrhosis, liver
      failure, and hepatocellular carcinoma. A minority of patients have a sustained
      response to antiviral therapy, and nonresponders remain at risk of developing
      progressive liver disease. We conducted a randomized, controlled trial of therapy
      with the combination of interferon (IFN) and ribavirin in patients with chronic
      hepatitis C who had not responded to an initial course of therapy with IFN alone.
      A total of 124 patients were randomized to receive the combination of IFN and
      ribavirin for either 24 or 48 weeks and followed for an additional 24 weeks after
      stopping therapy. Thirty-eight treated patients (30.6%) achieved a sustained
      virologic response (undetectable HCV RNA at the 24-week follow-up point). This
      was associated with significant improvement in necroinflammatory activity noted
      on liver biopsy. Interestingly, there was not a statistically significant
      difference in response rates based on the duration of treatment; HCV genotype was
      the strongest predictor of a sustained response. Sustained responses were noted
      even in patients with poor predictive factors, including those with advanced
      hepatic fibrosis or cirrhosis, high levels of HCV RNA in serum, and those
      infected with HCV genotype 1. The study included 24 patients with normal serum
      alanine transaminase (ALT) values before therapy who had similar responses to
      those with initially elevated transaminase values. This study suggests that the
      combination of IFN and ribavirin is a useful modality of therapy in patients with
      chronic hepatitis C who did not respond to IFN alone.

PMID- 11230752
TI  - Interleukin 10 polymorphisms as predictors of sustained response in antiviral
      therapy for chronic hepatitis C infection.
AB  - Host genetic factors have been reported to influence the natural history of
      hepatitis C virus (HCV) infection. We examined whether variation in interleukin
      10 (IL-10) and tumor necrosis factor alpha (TNF-alpha) genes would predict the
      likelihood of sustained response to antiviral therapy. Single nucleotide
      polymorphisms (SNPs) and microsatellites at two loci encoding the cytokines IL-10
      and TNF-alpha were determined by polymerase chain reaction (PCR)-based
      techniques. Their relationship to the outcome of antiviral therapy for chronic
      HCV infection was studied in 49 white patients who had a virologically sustained
      response (SR) and in 55 white nonresponders (NR) to a combination of interferon
      alfa-2b and ribavirin (IFN + R). Several IL-10 variants were more frequent among
      SRs compared with NRs. Carriage of the -592A or the -819T SNP was associated with
      SR (odds ratio [OR] = 2.2; P =.016). The -592A/A and the exclusively linked 
      819T/T genotypes were also associated with SR (OR = 16.6; P =.013 for either).
      The haplotype consisting of the 108-bp IL-10.R microsatellite and -3575T, -2763C,
      -1082A, -819T, -592A was also associated with SR (OR = 2.65; P =.01).
      Stratification for viral genotype, baseline viral RNA concentration, and
      histologic status identified homozygosity for the haplotype as the principal
      determinant: all 5 homozygous individuals achieved SR (OR(crude) = 13.7; P =.025;
      stratified ORs = 1.9-7.0), whereas heterozygotes differed only slightly from wild
      type carriers. In contrast, TNF alleles defined by promoter sequences -238G/A and
      -308G/A were approximately equally distributed among SR and NR. In conclusion,
      homozygosity for -592A, -819T or the extended haplotype (108bp) - (-2575T) - (
      2763C) - (-1082A) - (-819T) - (-592A) is associated with SR to IFN + R.

PMID- 11230754
TI  - Biliary cyst fluid from common bile duct-ligated rats stimulates endothelial
      nitric oxide synthase in pulmonary artery endothelial cells: a potential role in
      hepatopulmonary syndrome.
AB  - The hepatopulmonary syndrome (HPS) results from pulmonary microvascular
      dilatation in cirrhosis and is associated with increased pulmonary endothelial
      nitric oxide synthase (eNOS) levels. In the common bile duct ligation (CBDL)
      model, endothelin-1 (ET-1) released from the liver contributes to the rise in
      pulmonary eNOS and intrapulmonary vasodilatation. Whether substances, including
      ET-1, are found in the biliary tree and selectively enter the circulation after
      CBDL to influence the pulmonary vasculature is unknown. We assessed if control
      bile and fluid obtained from the obstructed biliary tree in CBDL animals contains
      ET-1 and alters eNOS expression and activity in bovine pulmonary artery
      endothelial cells (BPAECs). Control bile and biliary cyst fluid contained
      concentrations of ET-1 25- to 42-fold normal plasma levels, and hepatic venous
      concentrations of ET-1 were selectively increased after CBDL. Biliary cyst fluid
      caused a dose-dependent induction of eNOS messenger RNA (mRNA) (1.9-fold
      control), protein (2.5-fold control), and enzyme activity (2.2-fold control)
      maximal at a 1:10 dilution. The increases were associated with enhanced nitric
      oxide (NO) production (3.1-fold control) and were inhibitable with an ET(B)
      receptor antagonist. Bile from sham and portal vein-ligated animals did not
      increase eNOS expression and at dilutions of 1:100 and 1:10 caused cell toxicity.
      These results show that bile and biliary cyst fluid contain high concentrations
      of ET-1 that are specifically increased in hepatic venous blood after CBDL.
      Biliary cyst fluid increases eNOS expression and activity in an ET(B) receptor
      dependent manner in BPAECs. The findings suggest a novel mechanism for the
      susceptibility of CBDL animals to the HPS.

PMID- 11230753
TI  - Agonist-specific regulation of monocyte chemoattractant protein-1 expression by
      cyclooxygenase metabolites in hepatic stellate cells.
AB  - Activated hepatic stellate cells (HSC) regulate the liver "wound-healing"
      response through expression of chemokines, including monocyte chemoattractant
      protein-1 (MCP-1), which participate in the formation of the inflammatory
      infiltrate during liver injury. Cyclooxygenase (COX) catalyzes the conversion of
      arachidonic acid into prostaglandins, which may contribute to the inflammatory
      response. In this study, we investigated the effects of COX inhibitors on the
      expression of MCP-1 in cultured HSC. Pretreatment of HSC with nonspecific COX
      inhibitors such as indomethacin or ibuprofen markedly reduced the expression of
      MCP-1 caused by exposure to tumor necrosis factor alpha (TNF-alpha) or
      interleukin-1alpha (IL-1alpha). NS-398, a specific COX-2 inhibitor, also resulted
      in a dose-dependent inhibition of MCP-1 gene and protein expression. These
      effects were dependent on reduced MCP-1 transcription, as established using a
      reporter plasmid. In contrast, the up-regulation of MCP-1 expression caused by
      interferon gamma (IFN-gamma) was not sensitive to COX inhibitors. Quiescent HSC
      did not show detectable expression of COX-2, which became evident after
      activation in culture, and while TNF-alpha and IL-1alpha markedly increased the
      expression of COX-2, IFN-gamma did not have any effects. Pretreatment of HSC with
      the stable cyclic adenosine monophosphate (cAMP) analog, 8-bromo cAMP, reverted
      the effects of the COX-2 inhibitor, but not of a nuclear factor-kappaB (NF
      kappaB) inhibitor, demonstrating that prostaglandins modulate MCP-1 expression
      via production of cAMP. On the other hand, the action of NF-kappaB inhibitors was
      negligible in IFN-gamma-stimulated cells. These findings indicate that cross-talk
      between cytokines and a prostaglandin-cAMP pathway differentially regulates the
      proinflammatory potential of HSC, contributing to the modulation of liver tissue
      inflammation.

PMID- 11230755
TI  - Mutational analysis of the structure and functions of hepatitis C virus RNA
      dependent RNA polymerase.
AB  - The hepatitis C virus (HCV) nonstructural protein 5B (NS5B) is an RNA-dependent
      RNA polymerase (RdRP), a central catalytic enzyme for HCV replication. To further
      understand the structure and functions of NS5B, we introduced a series of 27
      clustered and 19 point substitution mutations within and outside the well-known
      motifs conserved among RdRP by alanine scanning and investigated effects of these
      mutants on enzymatic activity of NS5B. Surprisingly, most of the mutations (22 of
      27 clustered mutants) do not affect RdRP activity at all, indicating that the
      side chains of the corresponding amino acid residues are dispensable for the
      catalytic activity. On the other hand, 4 mutants, cm20t, cm194t, cm2t, and cm3t,
      are defective in RdRP activity. By further analysis with point mutations within
      these regions, E18, Y191, C274, Y276, and H502 were determined to be critical for
      the RdRP activity. Y276 was also shown to be critical for RNA template/primer
      association, although 3 amino acid sequences were identified to be important for
      RNA template binding by RNA-filter binding assays. Finally, 4 discontinuous
      sequences of NS5B (aa139-145, aa149-155, aa 365-371, and aa 382-388) were found
      to be essential for binding to NS5A as determined by glutathione S-transferase
      (GST)-pull down assays using GST-NS5A and FLAG-NS5B expressed in cotransfected
      cells, and GST-pull down assay in vitro. In light of the crystal structure models
      of NS5B recently reported, our results indicate that the RdRP activity of NS5B
      requires the longer loop and the helix located at the distal of the thumb, which
      are unique among RdRPs as well as reverse transcriptases.

PMID- 11230756
TI  - Heterogeneity and plasticity of hepatocyte lineage cells.
AB  - It is hypothesized that the liver has 3 levels of cells in the hepatic lineage
      that respond to injury or carcinogenesis: 1) the mature hepatocyte, which
      responds to partial hepatectomy (PH), to centrolobular injury, such as that
      induced by carbon tetrachloride (CCl(4)), and to dimethylnitrosamine (DEN)
      hepatocarcinogenesis; 2) the ductular "bipolar" progenitor cell, which responds
      to centrolobular injury when the proliferation of hepatocytes is inhibited, and
      to N-2-acetylaminofluorene (AAF) hepatocarcinogenesis; and 3) the putative
      periductular stem cell, which responds to periportal injury, such as induced by
      allyl alcohol and to choline-deficiency models of hepatocarcinogenesis.
      Hepatocytes are numerous, respond rapidly by 1 or 2 cell cycles, but can only
      produce other hepatocytes. The ductular progenitor cells are less numerous, may
      proliferate for longer times than hepatocytes, and are generally considered
      "bipolar," i.e., can give rise to biliary cells or hepatocytes. Periductular stem
      cells are rare in the liver, have a very long proliferation potential, and may be
      multipotent, but their full potential has yet to be defined. Extrahepatic (bone
      marrow) origin of the periductular stem cells is supported by recent data showing
      that hepatocytes may express genetic markers of donor hematopoietic cells after
      bone marrow transplantation. Thus, experimental models of liver injury and of
      hepatocarcinogenesis may call forth a cellular response at different levels in
      the hepatic lineage (heterogeneity), and these cells have different potential to
      form cells of other types (plasticity).

PMID- 11230758
TI  - Advancing the bile-ology of cholestatic liver disease.

PMID- 11230757
TI  - Nomenclature for antiviral-resistant human hepatitis B virus mutations in the
      polymerase region.
AB  - There is currently no universally accepted numbering convention for the antiviral
      drug-related resistance mutations in the reverse transcriptase (rt) domain of the
      human hepatitis B virus (HBV) polymerase. The published inconsistencies have
      resulted from different HBV genotypes. A standardized numbering system for HBV
      polymerase is proposed. The new system is based on functional observations of HBV
      surface gene proteins (preS1, preS2, and HBsAg) and on the current convention
      used for human immunodeficiency virus type 1 (HIV-1) polymerase proteins
      (protease, rt, and integrase), in which the amino acid numbering restarts at the
      first codon position of each domain. The HBV polymerase protein can be divided
      into 4 domains (terminal protein, spacer, rt, ribonuclease H) and each of these
      can be numbered separately. In this proposal, the HBV rt domain starts with the
      highly conserved EDWGPCDEHG motif, contains 344 amino acids, and the lamivudine
      related resistance mutations are found at amino acid rtL180M (previously amino
      acid 528, 526, 515, or 525) and rtM204V/I (previously 552, 550, 539, or 549). The
      new consensus rt domain numbering system is genotype independent and allows
      investigators to number any previously and newly discovered antiviral-related
      amino acid change in a standardized manner.

PMID- 11230759
TI  - The ACAT2 gene encodes a gatekeeper of intestinal cholesterol absorption that
      regulates cholesterolemia and gallstone disease.

PMID- 11230760
TI  - A confluence of epidemics: does hepatitis C cause type 2 diabetes?

PMID- 11230761
TI  - The risks of percutaneous liver biopsy.

PMID- 11230763
TI  - Polymorphism in the promoter region of the bilirubin UDP-glucuronosyltransferase
      (Gilbert's syndrome) in healthy Dutch subjects.

PMID- 11230764
TI  - Prepubic urethrostomy: A long-term study in 16 cats.
AB  - OBJECTIVE: To investigate the indications for and long-term outcome of prepubic
      urethrostomy (PPU) in the cat. STUDY DESIGN: Retrospective survey. ANIMALS:
      Sixteen cats that had undergone PPU. METHODS: Data were recovered from the
      medical records of the cats. Follow-up information was obtained from the owners
      and referring veterinarians. RESULTS: Indications for PPU were: failed perineal
      urethrostomy for the management of idiopathic lower urinary tract disease (ILUTD)
      (8 cats) or urethral trauma (1 cat); unresolved pelvic urethral obstruction after
      recurrent ILUTD (5 cats); and stenosis of the pelvic urethra as a result of
      trauma (2 cats). A patent urethral stoma was created in all cases. Signs of lower
      urinary tract disease were present in 8 cats postoperatively. With appropriate
      dietary management, these signs resolved in 2 cats and improved in another 4
      cats. Eleven cats experienced postoperative complications that consisted of
      peristomal skin irritation or necrosis (7 cats) and urinary incontinence (6
      cats). Complications developed in the immediate postoperative period in 6 cats,
      and resolved in 2 of these. Six cats developed late complications, at 6 to 84
      months postoperatively. Six cats were euthanatized between 1 and 26 months'
      postoperatively. The mean survival time in these cats was 13 months. Reasons for
      euthanasia included urinary incontinence (3 cats), skin necrosis (2 cats), and
      unresolvable ILUTD (1 cat). CONCLUSIONS: PPU is a salvage procedure that is
      successful in relieving the signs of urinary tract obstruction and preventing
      further obstruction. However, potential complications should limit its use to
      cases in which standard techniques for perineal urethrostomy cannot be performed.
      CLINICAL RELEVANCE: PPU is a comparatively simple procedure that should be
      considered as a salvage technique for obstructive disease of the pelvic urethra.

PMID- 11230765
TI  - Serosal injury in the equine jejunum and ascending colon after ischemia
      reperfusion or intraluminal distention and decompression.
AB  - OBJECTIVE: To document morphologic changes that occur in equine intestinal serosa
      after experimentally induced ischemia and subsequent reperfusion (jejunum,
      ascending colon) or after intraluminal distention and decompression (jejunum).
      STUDY DESIGN: Morphologic effects of ischemia-reperfusion or intraluminal
      distention-decompression determined on the serosal layer of the equine jejunum.
      The large colon serosa was evaluated after ischemia-reperfusion injury. ANIMALS
      OR SAMPLE POPULATION: Seven adult horses. METHODS: After induction of general
      anesthesia and ventral median celiotomy, ischemia was created by arteriovenous
      (AVO) and lumen occlusion of a 20-cm segment of jejunum and ascending colon for
      70 minutes, followed by a 60-minute reperfusion period. Intraluminal distention
      (25 cm H2O) was created in a second 20-cm jejunal segment and maintained within
      the abdomen for 120 minutes, followed by a 120-minute decompression period.
      Seromuscular biopsies were obtained upon entering the abdomen and after the
      ischemic and reperfusion periods, and after the distention and decompression
      periods along with corresponding control seromuscular biopsies. Samples were
      processed and examined by light microscopy, transmission electron, and scanning
      electron microscopy. RESULTS: Ischemia and reperfusion, and intraluminal
      distention and decompression, resulted in severe morphologic changes in the
      seromuscular layer of equine jejunum. A similar period of ischemia-reperfusion
      caused minimal changes in the ascending colon serosa. CONCLUSION: Adult equine
      jejunum sustains more serosal damage than the ascending colon after similar
      periods of ischemia-reperfusion injury. Intraluminal distention and subsequent
      decompression causes serosal damage in the equine jejunum. CLINICAL RELEVANCE:
      The small intestine is more susceptible to seromuscular layer damage than the
      ascending colon.

PMID- 11230766
TI  - The effect of implanting gentamicin-impregnated polymethylmethacrylate beads in
      the tarsocrural joint of the horse.
AB  - OBJECTIVE: To determine the effect of intra-articular gentamicin-impregnated
      polymethylmethacrylate (PMMA) beads inserted in the equine tarsocrural joint on
      the synovial fluid, synovial lining, and cartilage, and to determine the peak and
      sustainable gentamicin concentrations in synovial fluid and plasma. STUDY DESIGN:
      Pharmacokinetic, cytologic, and histologic study of the effect of gentamicin
      impregnated PMMA on normal equine tarsocrural joints. ANIMALS: Five healthy adult
      horses. METHODS: Gentamicin-impregnated PMMA bead strands (3 strands each of 40
      beads, with each strand containing 100 mg gentamicin) were surgically inserted
      into one radiographically normal tarsocrural joint in 5 horses. Each horse had
      both joints flushed with 1 L of lactated Ringer's solution before bead
      administration. Synovial fluid total protein concentration, white blood cell
      (WBC) count, gentamicin concentration, synovial histology, cartilage integrity,
      and cartilage glycosaminoglycan (GAG) concentrations were determined. RESULTS:
      Gentamicin concentration (mean +/- SEM peak concentration, 27.9 +/- 2.27
      microg/mL) occurred in the first 24 hours and remained above 2 microg/mL for 9
      days. Gentamicin concentrations in control joints and the plasma remained below
      detectable levels. The synovial fluid WBC count for treated joints was increased
      compared with control joints for 72 hours, but was similar at day 6. The synovial
      protein concentration in gentamicin-treated joints remained increased for 21
      days. Synovium in treated joints had diffuse synovitis, whereas control joints
      had less fibrovascular proliferation. Superficial cartilage erosion was present
      in all treated joints. There was no difference in the GAG content of treated and
      control joint cartilage. CONCLUSIONS: Short-term implantation of gentamicin (300
      mg)-impregnated PMMA beads can provide therapeutic levels of gentamicin (>2
      microg/mL) in the normal tarsocrural joint for 9 days; however, gentamicin
      impregnated PMMA beads induce synovitis and superficial cartilage erosion.
      CLINICAL RELEVANCE: Temporary intra-articular administration of antibiotic
      impregnated PMMA may be an effective way to treat septic joints that require
      constant high concentrations of antibiotics.

PMID- 11230767
TI  - The effects of doxycycline on nitric oxide and stromelysin production in dogs
      with cranial cruciate ligament rupture.
AB  - OBJECTIVE: To investigate the potential of doxycycline to reduce stromelysin and
      inducible nitric oxide synthase (iNOS) activity in dogs with osteoarthritis (OA)
      secondary to spontaneous cranial cruciate ligament (CCL) rupture. STUDY DESIGN:
      Prospective, clinical study. ANIMALS: Eighty-one dogs with OA secondary to CCL
      rupture and 54 normal dogs. METHODS: Dogs with OA secondary to CCL rupture were
      divided into 2 groups before surgery. The Doxy-CCl group received 3 to 4 mg/kg
      doxycycline orally every 24 hours for 7 to 10 days (n = 35). The CCL group
      received no treatment (n = 46). Synovial fluid, articular cartilage, synovial
      membrane, and CCL samples were collected during surgery (Doxy-CCL group and CCL
      group) or immediately after euthanasia from healthy dogs (control group).
      Synovial fluid samples were examined cytologically. Total nitric oxide (NOt)
      concentrations were measured in the supernatant of explant cultures of all tissue
      samples, and stromelysin activity was measured in the supernatant of explant
      cultures of cartilage. RESULTS: NOt concentrations measured in cartilage were
      significantly lower in the Doxy-CCL group than in the CCL group, but were not
      different from those measured in the control group. Doxycycline treatment did not
      have a significant effect on cartilage stromelysin levels. CONCLUSION: The
      findings in this study indicate that doxycycline inhibits NO production in
      cartilage in dogs with CCL rupture. CLINICAL RELEVANCE: Doxycycline may have a
      role in the treatment of canine OA by inhibiting NO production.

PMID- 11230768
TI  - Comparison of trochlear block recession and trochlear wedge recession for canine
      patellar luxation using a cadaver model.
AB  - OBJECTIVE: To compare trochlear block recession (TBR) to trochlear wedge
      recession (TWR) with regards to patellar depth (percentage of patellar volume
      under the trochlear ridges), patellar articular contact, percentage of recessed
      trochlear surface area, and resistance to patellar luxation. STUDY DESIGN: In
      vitro computed tomography (CT) and biomechanical evaluation using a cadaver
      model. SAMPLE POPULATION: Twelve normal, large-breed canine cadavers. METHODS:
      Bilateral pelvic limb specimens with intact stifle joints were mounted on a
      positioning device. The femoral trochlear ridges were reduced to provide a
      standard shallow trochlea. TBR or TWR was performed to a standard depth randomly
      on paired specimens. CT and biomechanical evaluations were performed pre- and
      postoperatively in both an extended (148 degrees ) and flexed (113 degrees )
      stifle position. CT images were digitized and measurements made using an image
      analysis software program. Biomechanical testing consisted of applying 40 degrees
      of internal tibial rotation and documenting patellar luxation. RESULTS: The
      change in trochlear depth (depth of recession) was not significantly different
      between groups. In the extended stifle position (patella in the proximal
      trochlea), patellar depth and patellar articular contact with the recessed
      trochlea were significantly greater after TBR compared with TWR. The percentage
      of recessed trochlear surface area was significantly greater after TBR compared
      with TWR. In the extended position, a smaller percentage of the patellae luxated
      within 40 degrees of internal tibial rotation after TBR compared with TWR.
      CONCLUSIONS: TBR increases proximal patellar depth, increases patellar articular
      contact with the recessed proximal trochlea, recesses a larger percentage of
      trochlear surface area, and results in a greater resistance to patellar luxation
      in an extended position as compared with TWR. CLINICAL RELEVANCE: TBR may help
      limit the development of stifle DJD in dogs treated for canine patellar luxation.

PMID- 11230769
TI  - Clinical experiences with axial deviation of the aryepiglottic folds in 52
      racehorses.
AB  - OBJECTIVE: To describe the clinical findings in 52 racehorses with axial
      deviation of the aryepiglottic folds (ADAF) and to report outcome in 33 of these
      horses after either rest or transendoscopic laser excision of aryepiglottic fold
      tissue. STUDY DESIGN: Retrospective study. ANIMAL OR SAMPLE POPULATION:
      Racehorses admitted for high-speed treadmill (HST) evaluation of poor
      performance. METHODS: Medical records and videotapes of resting and exercising
      videoendoscopic examinations were reviewed. Racing performance records and owner
      or trainer interviews, at least 1 year after HST examination, were used to
      compare results after either surgical management or rest in 33 horses with ADAF
      and no other upper-airway abnormalities. RESULTS: ADAF occurred in 6% of horses
      evaluated for poor performance. No breed or gender predisposition existed, but
      horses with ADAF were younger than the overall population evaluated on the HST.
      Of 52 horses with ADAF, 19 horses had at least one other upper-airway
      abnormality. There was no apparent association between ADAF and other causes of
      dynamic upper-respiratory obstruction. Surgical correction was successfully
      performed in standing or anesthetized horses without complications. When ADAF was
      the only upper-airway obstruction, 75% of horses that had surgery and 50% of
      rested horses had objective improvement in performance. Owners and trainers also
      perceived greater improvement in performance in horses that had surgery.
      CONCLUSIONS: Whereas surgical management of ADAF is recommended, clinical
      experience indicated that it is not required to resolve ADAF in all horses.
      However, owners and trainers of horses that had surgery were more satisfied with
      outcome than those with horses managed conservatively. CLINICAL RELEVANCE:
      Diagnosis of ADAF can only be made by videoendoscopic evaluation during high
      speed exercise. Transendoscopic laser excision of the collapsing portion of the
      aryepiglottic folds can be performed safely in standing horses and results in
      resolution of airway obstruction and rapid return to training.

PMID- 11230770
TI  - Evaluation of a portocaval venograft and ameroid ring for the occlusion of
      intrahepatic portocaval shunts in dogs.
AB  - OBJECTIVE: To evaluate the use of a portocaval venograft and ameroid constrictor
      in the surgical management of intrahepatic portosystemic shunts (PSS). STUDY
      DESIGN: Prospective, clinical study. ANIMAL POPULATION: Ten client-owned dogs
      with intrahepatic PSS. METHODS: Portal pressure was measured after temporary
      suture occlusion of the intrahepatic PSS. In dogs with an increase in portal
      pressure greater than 8 mm Hg, a single extrahepatic portocaval shunt was created
      using a jugular vein. An ameroid ring was placed around the venograft and the
      intrahepatic PSS was attenuated. Transcolonic pertechnetate scintigraphy was
      performed before surgery, 5 days after surgery, and 8 to 10 weeks after surgery.
      Dogs with continued portosystemic shunting were evaluated further by laparotomy
      or portography. Clinical outcome and complications were recorded. RESULTS: Mean
      (+/- SD) portal pressure increased from 6 +/- 3 to 19 +/- 6 mm Hg with PSS
      occlusion; in all 10 dogs, the increase in portal pressure was greater than 8 mm
      Hg. There were no intraoperative complications, and, after creation of the
      portocaval shunt, the intrahepatic PSS could be completely ligated in 8 of 10
      dogs. The final portal pressure was 9 +/- 4 mm Hg. Postoperative complications
      included coagulopathy and death (1 dog), ascites (3 dogs), and incisional
      discharge (3 dogs). Five of 8 dogs had continued portosystemic shunting at 8 to
      10 weeks after surgery. Multiple extrahepatic PSS were demonstrated in 4 of these
      dogs. Clinical outcome was excellent in all 9 surviving dogs. CONCLUSIONS AND
      CLINICAL SIGNIFICANCE: The surgical technique resulted in a high incidence of
      multiple extrahepatic PSS. Short-term clinical results were promising, but long
      term outcome must be evaluated further.

PMID- 11230771
TI  - Effects of 3.3-MHz ultrasound on caudal thigh muscle temperature in dogs.
AB  - OBJECTIVE: To examine the tissue-temperature changes that occur at various depths
      during 3.3-MHz ultrasound (US) treatments of the caudal thigh muscles in dogs.
      STUDY DESIGN: A prospective, randomized, experimental study. ANIMALS: Ten mixed
      breed research dogs. METHODS: Two US treatments, one at an intensity of 1.0
      W/cm(2) and one at 1.5 W/cm2, were administered to the caudal thigh region of 10
      adult male and female hound-type dogs weighing 20.5 to 25.0 kg. Needle
      thermistors were inserted in the caudal thigh muscles below the skin surface at
      depths of 1.0, 2.0, and 3.0 cm, directly under the US treatment area. Both
      intensities of US treatment were performed on each dog over a 10-cm2 area for 10
      minutes using a sound head with an effective radiating area of 5 cm2. Treatments
      were administered in random order. Tissue temperature was measured before,
      during, and after US treatment until tissue temperature returned to baseline.
      RESULTS: At the completion of the 10-minute US treatment, the temperature rise at
      an intensity of 1.0 W/cm2 was 3.0 degrees C at the 1.0-cm depth, 2.3 degrees C at
      2.0-cm depth, and 1.6 degrees C at 3.0-cm depth. At an intensity of 1.5 W/cm2,
      temperatures rose 4.6 degrees C at the 1.0-cm depth, 3.6 degrees C at 2.0-cm
      depth, and 2.4 degrees C at 3.0-cm depth. Tissue temperatures returned to
      baseline within 10 minutes or sooner after treatment in all dogs. CONCLUSIONS:
      This study demonstrates that significant heating occurs in the superficial thigh
      muscle of dogs during 3.3-MHz US. CLINICAL RELEVANCE: 3.3-MHz US can be used to
      increase superficial tissue temperature in dogs, although the amount of time that
      tissue temperature remains elevated is relatively short.

PMID- 11230772
TI  - Thoracoscopic-assisted diaphragmatic hernia repair using a thoracic rib
      resection.
AB  - OBJECTIVE: To describe the surgical treatment of a dorsal diaphragmatic hernia in
      an adult horse using thoracic rib resection aided by thoracoscopy and a flank
      incision. STUDY DESIGN: Case report. ANIMAL POPULATION: One client-owned horse.
      RESULTS: A six-year-old Dutch warmblood gelding was admitted for colic-associated
      colonic incarceration in a diaphragmatic hernia. Seven weeks after the initial
      colic surgery, the gelding underwent surgery to repair the defect. Thoracoscopy
      and a flank incision were used to identify the location of the hernia and the
      subsequent site of rib resection. The stomach was adhered to the edges of the
      defect, leaving only a small residual hole. Resection of the 14th rib provided
      excellent exposure of the defect and closure of the remaining hernia. CONCLUSION
      AND CLINICAL RELEVANCE: Thoracic rib resection can provide access to
      diaphragmatic hernias in adult horses. Thoracoscopy or a flank incision, or both,
      may aid in determining which rib is best resected.

PMID- 11230773
TI  - An in vitro biomechanical comparison of interlocking nail constructs and double
      plating for fixation of diaphyseal femur fractures in immature horses.
AB  - OBJECTIVE: To compare the biomechanical properties of intact immature horse
      femurs and 3 stabilization methods in ostectomized femurs. ANIMAL OR SAMPLE
      POPULATION: Eighteen pairs of femurs from immature horses aged 1 to 15 months,
      and weighing 68 to 236 kg. METHODS: Thirty-four immature horse femurs were
      randomly assigned to 1 of 5 test groups: 1) interlocking intramedullary nail
      (IIN) (n = 6); 2) IIN with a cranial dynamic compression plate (I/DCP) (n = 6);
      3) 2 dynamic compression plates (2DCP) (n = 8); 4) intact femurs tested to
      failure in lateromedial (LM) bending (n = 6); and 5) intact femurs tested to
      failure in caudocranial (CaCr) bending (n = 8). Mid-diaphyseal ostectomies (1 cm)
      were performed in all fixation constructs. Biomechanical testing consisted of 4
      nondestructive tests: CaCr bending, LM bending, compression, and torsion,
      followed by bending to failure. All groups were tested to failure in LM bending
      with the exception of 1 group of intact femurs tested to failure in CaCr bending.
      Stiffness and failure properties were compared among groups. RESULTS: The 2DCP
      femur construct had greater structural stiffness in nondestructive bending than
      the IIN-femur construct in either LM or CaCr bending, and the I/DCP-femur
      construct in LM bending. Only the I/DCP and 2DCP fixations were similar to intact
      bone in nondestructive-bending tests. In addition, the 2DCP-femur construct had
      greater structural and gap torsional stiffness than the I/DCP-femur construct,
      and greater gap torsional stiffness than the IIN-femur construct. However, all of
      the fixation methods tested, including the 2DCP-femur construct, had lower
      structural stiffness in torsional loading compared with intact bone. No
      significant differences in structural stiffness were found between intact bones
      and femur constructs tested nondestructively in compression. In resistance to LM
      bending to failure, the 2DCP-femur construct was superior to the IIN-femur
      construct, yet similar to the I/DCP-femur construct. Also, evaluation of yield
      and failure loads revealed no significant differences between intact bone and any
      of the femur constructs tested to failure in LM bending. CONCLUSIONS: In general,
      the 2DCP-femur construct provided superior strength and stiffness compared with
      the IIN and I/DCP-femur constructs under bending and torsion. CLINICAL RELEVANCE:
      Double plating of diaphyseal comminuted femoral fractures in immature horses may
      be the best method of repair, because in general, it provides the greatest
      strength and stiffness in bending and torsion.

PMID- 11230774
TI  - Endogenous nitric oxide production in canine osteoarthritis: Detection in urine,
      serum, and synovial fluid specimens.
AB  - OBJECTIVE: To measure nitric oxide (NO) concentrations in serum, urine, and
      synovial fluid (SF) of dogs with naturally occurring cranial cruciate ligament
      (CCL) rupture and normal dogs, and to compare these with clinical and histologic
      changes of osteoarthritis (OA). STUDY DESIGN: Prospective clinical study
      including 2 groups of animals selected from the hospital population. ANIMALS:
      Forty-three dogs (CCL group) with OA secondary to CCL rupture; 30 healthy dogs
      (control group) without CCL rupture. METHODS: Serum, urine, and SF were collected
      before and during surgery in the CCL group or immediately after euthanasia in the
      control group. Articular cartilage and synovial membrane tissue specimens were
      prepared for routine histologic examination. The stable end products of NO, total
      nitrite and nitrate (NOt) activity, were measured in body fluids and compared
      with macroscopic and histologic degrees of OA. Urinary NOt concentration was
      compared with urinary creatinine concentration and stated as urinary
      NOt:creatinine ratio (UNCR). RESULTS-SF NOt concentrations were not significantly
      different between the 2 groups. Serum NOt concentrations (45.6 vs 28.9
      micromol/L; P =.042) and the UNCR (0.007 vs 0.004; P =.035) were significantly
      higher in dogs of the CCL group compared with the control population. An
      association between UNCR and histologic and macroscopical OA grades could be
      demonstrated. CONCLUSION: UNCR might be a useful indicator of nitrite and nitrate
      production and, therefore, osteoarthritic changes in joints. CLINICAL RELEVANCE:
      UNCR could be used as a tool to evaluate the NOt production by joint tissues over
      time and might therefore provide a method of evaluating the effects of drugs in
      the control of osteoarthritis.

PMID- 11230775
TI  - Suppression of apoptosis is responsible for increased thickness of intestinal
      mucosa in streptozotocin-induced diabetic rats.
AB  - Intestinal mucosal growth is a common, but uncharacterized, observation
      associated with diabetes mellitus. Epithelial homeostasis is balanced by
      regulation of cell proliferation and cell death. To determine the contribution of
      apoptosis to the overall maintenance of intestinal growth, we examined intestinal
      apoptosis in the well-characterized streptozotocin (STZ)-induced diabetes rat
      model. Rats were injected with STZ (75 mg/kg body weight), thereafter they were
      allowed free feeding or restricted feeding for 3 weeks. Food intake and
      intestinal mucosal height were evaluated. In a second experiment, additional
      groups of animals were injected with STZ and were fed ad libitum for 1 or 3
      weeks. Ornithine decarboxylase (ODC) activity, ratio of fragmented DNA to total
      DNA, electrophoresis of fragmented DNA, and Western blot analysis of caspase-3
      were examined. Food intake gradually increased in free-feeding rats after
      induction of diabetes. Intestinal mucosal height in free-feeding diabetic rats
      was approximately 25% longer than controls, but this increase in mucosal height
      was not observed in restricted-fed diabetic rats (25 g/d). ODC activity in
      intestinal mucosa in diabetic rats did not differ from that of control rats.
      Percent fragmented DNA of diabetic rats 1 week after STZ injection was
      significantly lower than that of control rats, and this decrease returned to the
      control level 3 weeks after STZ treatment. Active form of caspase-3 was
      attenuated 1 week after drug treatment. Attenuated effect of diabetic rats on
      intestinal apoptosis did not affect increased apoptosis after ischemia
      reperfusion. Suppression of apoptosis in the early days of STZ-induced diabetes
      was responsible for the increased mucosal height in the small intestine in STZ
      induced diabetic animals.

PMID- 11230776
TI  - Body composition and energy balance: lack of effect of short-term hormone
      replacement in postmenopausal women.
AB  - Postmenopausal women (PMW) commonly believe that hormone replacement (HR) leads
      to weight gain, and fear of weight gain and/or an actual increase in weight is
      one of the principle reasons evoked for the discontinuation of HR. However, the
      potential effects of physiologic HR on body composition have yet to be separated
      from the effects of lifestyle or aging. Therefore, we examined the effect of
      short-term hormone replacement and age on alterations in weight, body
      composition, and energy balance. A prospective study of 28 healthy PMW aged 45 to
      55 years (younger PMW, studies completed n = 18) and 70 to 80 years (older PMW,
      studies completed n = 15) was conducted. The last menstrual period was more than
      12 months previously. The women had a body mass index (BMI) less than 30 kg/m(2)
      and were taking no medication. Subjects were studied at baseline, after 1 month
      of transdermal estrogen (Estraderm, 50 microg/day) administration (E2), followed
      by a further month of transdermal estrogen with progesterone (100 mg per vagina
      twice daily) for the final 7 days (E2 + P). Anthropometric measurements and
      energy assessments were performed at each visit. Physiologic HR was achieved in
      each subject, and there was no difference between levels achieved in older and
      younger women. Resting energy expenditure and activity level were positively
      correlated with fat-free mass (P <.0001), while energy intake was not. Resting
      energy expenditure was lower in older compared with younger PMW when adjusted for
      fat-free mass (P <.005). Energy intake was also lower in the older PMW when
      corrected for fat-free mass (P <.0001); as was activity level (P <.05). There was
      no effect of hormonal treatment on any of the parameters measured. Changes in
      weight from baseline for E2 (0.37 +/- 0.25 and 0.61 +/- 0.27 kg in younger and
      older) and E2 + P (0.11 +/- 0.38 and 0.28 +/- 0.31 kg) were not statistically
      significant. In addition, there was no difference in BMI, fat mass, fat-free
      mass, total body water, or waist-to-hip ratio (WHR) between groups or with
      hormonal treatment. In conclusion, short-term transdermal HR is not associated
      with significant changes in weight or other anthropometric measures in younger or
      older PMW. These studies confirm the decrease in energy expenditure that occurs
      with aging, but indicates that there is no effect of HR on resting energy
      expenditure.

PMID- 11230777
TI  - Total cell-associated Zn2+ and Cu2+ and proliferative responsiveness of
      peripheral blood mononuclear cells from patients on chronic hemodialysis.
AB  - We investigated total copper (Cu2+) and zinc (Zn2+) content in plasma and
      peripheral blood mononuclear cells (PBMC) and its impact on proliferative ability
      of the latter in patients on chronic hemodialysis versus age- and sex-matched
      healthy volunteers. Plasma levels of Cu2+ and Zn2+ were significantly lower in
      dialysis patients compared with the control group (83.6 +/- 7.29 v 95.1 +/- 9.63
      microg/dL, P <.03 for Cu2+; 71.1 +/- 7.64 v 89.7+/- 12.55 microg/dL, P <.005 for
      Zn2+). Basal total PBMC-associated Cu2+ content was significantly higher in
      uremic patients (19.3 +/- 3.59 v 14.6 +/- 2.72 micromol/mg protein, P <.005).
      Basal PBMC-associated Zn2+ concentration was also significantly elevated in
      hemodialysis patients compared with their healthy counterparts (23.9 +/- 5.64 v
      10.5 +/- 2.64 micromol/mg protein, P <.005). In addition, we incubated PBMC of
      the uremic patients versus healthy control PBMC in a Zn2+ free versus Zn2+
      enriched medium. After a 72-hour incubation, total cell-associated Zn2+ of both
      normal and uremic cell populations increased significantly compared with the
      respective baselines (34.6 +/- 22.49 v 4.3 +/- 1.42 and 20.3 +/- 10.71 v 5.8 +/-
      2.22 micromol/mg protein, respectively). However, no statistically significant
      difference was evident between the 2 groups (34.6 +/- 22.49 v 20 +/- 10.7
      micromol/mg protein). Total cell Zn2+ content, on the other hand, was
      significantly increased in uremic PBMC after 72 hours of incubation in Zn2+
      enriched medium compared with the control group (63.3 +/- 26.12 v 18.6 +/- 13.42
      micromol/mg protein, P <.005). A significant increase in PBMC proliferation
      evaluated by 3H-thymidine incorporation was evident in the Zn2+ enriched culture
      (35,559 +/- 4,136 counts per minute [CPM] v 20,497 +/- 7,263 CPM, P <.005). Cu2+
      enrichment of the medium, while resulting in a modest elevation of cell
      associated Cu2+, did not produce such a proliferative effect.

PMID- 11230778
TI  - Influence of remnant accumulation markers on plasma concentrations of two
      lipoprotein(a) subspecies (containing or free of apoE).
AB  - Lipoprotein(a) [Lp(a)], an atherosclerosis marker, has 2 subspecies differing in
      structure and composition that can easily be distinguished by the presence or
      absence of apolipoprotein E (apoE). The subspecies containing apo E [Lp(a):B:E]
      is found mainly in the very-low-density lipoprotein (VLDL) size range, while that
      free of apoE [Lp(a):B] is found mainly in the LDL size range. As little is known
      about the physiologic function of these subspecies, this study investigated
      Lp(a):B and Lp(a):B:E concentrations in a population of normotriglyceridemic and
      moderately hypertriglyceridemic subjects in fasting state and attempted to
      determine the parameters influencing their plasma concentrations. The subjects
      studied (n = 98) had a mean total Lp(a) concentration of 108 mg/dL (28 to 252,
      minimum to maximum), a mean Lp(a):B concentration of 92.6 mg/dL (5 to 254), and a
      mean Lp(a):B:E concentration of 15.6 mg/dL (0 to 137). These results indicate
      that Lp(a):B:E, even in normolipidemic subjects, constitutes a detectable part of
      total Lp(a), ie, a mean percentage of 16.2% (0% to 96%). Multiple stepwise
      regression analyses showed that triacylglycerol has no independent effect on the
      concentration of Lp(a) subspecies, and that remnant accumulation markers, such as
      the E/LpB:E molar ratio (number of apoE per particle containing both apoB and
      apoE) and apoE-LpB (mass of apoE bound to particles containing both apoB and
      apoE), have a strong independent effect on this concentration. A strong positive
      influence of E/LpB:E on Lp(a):B:E subspecies was noted, as well as a negative
      influence of apo E-LpB on Lp(a):B subspecies. Taken together, these results
      suggest that the apoE bound to LpB:E particles plays a dominant role in the
      concentration of Lp(a) subspecies and that a redistribution of Lp(a) subspecies
      occurs under the influence of the apoE content of triacylglycerol-rich
      lipoprotein particles.

PMID- 11230779
TI  - Concentration of the complement activation product, acylation-stimulating
      protein, is related to C-reactive protein in patients with type 2 diabetes.
AB  - Type 2 diabetes is characterized by increased acute phase serum proteins. We
      wanted to study how these proteins are related to complement activation in type 2
      diabetes and how improvement of glycemic control affects them or complement
      activation. A total of 29 type 2 diabetic patients (age, 55.2 +/- 1.8 years,
      glycosylated hemoglobin [HbA(1c)] 8.9% +/- 0.2%, body mass index [BMI] 30.9 +/-
      0.8 kg/m(2), duration 5.9 +/- 1.3 years) participated in the study. They were
      previously treated either with diet alone or in combination with 1 oral
      antihyperglycemic medication. After a period of at least 4 weeks run-in on diet
      only, the patients were randomized to pioglitazone, glibenclamide, or placebo.
      Blood samples were taken before the treatments and at the end of the 6-month
      therapy. Basal C-reactive protein (CRP) level was related to acylation
      stimulating protein (ASP) concentration (r =.55, P <.01), and many acute phase
      serum protein concentrations were associated with each other. The treatment
      reduced HbA(1c) level in the pioglitazone (from 9.1 +/- 0.3% to 8.0 +/- 0.5%, P
      <.05) and glibenclamide (from 8.9 % +/- 0.3% to 7.7% +/- 0.2%, P <.05) groups.
      Glibenclamide treatment was associated with a reduction in alpha-1-antitrypsin (P
      <.05), ceruloplasmin (P <.01), and complement C3 protein (C3) (P <.05). Although
      ASP did not change significantly in any of the treatment subgroups, in the whole
      patient population, the change in HbA(1c) during the treatments correlated
      positively with the change in ASP, (r =.43, P <.05). The changes in many acute
      phase serum proteins and ASP were related to each other. In conclusion, (1)
      inflammatory factors and complement activation are associated in patients with
      type 2 diabetes, and (2) changes in hyperglycemia are related to changes in the
      concentration of the complement activation product, ASP.

PMID- 11230780
TI  - Effect of acquired immune deficiency syndrome wasting on the protein metabolic
      response to acute exercise.
AB  - Wasting is a major complication of human immunodeficiency virus (HIV) infection,
      which remains prevalent even in the era of highly-active antiretroviral therapy.
      We have previously shown that progressive resistance exercise can increase lean
      body mass (LBM) significantly in patients with wasting, and that exercise does
      not increase circulating HIV RNA concentrations. We examined the effect of 1 bout
      of moderately difficult exercise on whole body protein kinetics in 10 patients
      with HIV wasting and 12 patients with HIV infection without wasting. At baseline,
      there were no differences between the groups in whole body leucine flux,
      oxidation, or nonoxidative leucine disposal (NOLD, a measure of whole body
      protein synthesis). Six days after exercise, NOLD was significantly higher in the
      wasted patients compared with the nonwasted ones (82.2 +/- 16.7 v 66.5 +/- 15.2
      micromol/kg LBM/h, P <.03). The change in NOLD between baseline and day 6 was
      significantly different between the 2 groups (+9.0 +/- 9.2 v -3.3 +/- 5.7
      micromol/kg LBM/h, P <.02). These data indicate that the ability to respond to
      exercise with protein synthesis is maintained in HIV wasting.

PMID- 11230781
TI  - Protein restriction and dexamethasone as a model of protein hypercatabolism in
      dogs: effect of glutamine on leucine turnover.
AB  - To determine (1) whether protein restriction, combined with glucocorticosteroid
      treatment, can be used as a hypercatabolic model and (2) if so, whether glutamine
      attenuates protein wasting in this model, the effects of protein restriction,
      dexamethasone, and glutamine on leucine metabolism were assessed in dogs. A
      control group (n = 8) received a maintenance diet; another group (n = 8) received
      a protein-restricted diet either (1) alone; (2) along with a 7-day corticoid
      treatment; or (3) along with a 7-day corticoid treatment and a 7-hour intravenous
      (IV) glutamine infusion. The last day of each regimen, dogs underwent an IV
      isotope infusion in the fasting state, with a 3-hour NaH(13)CO3 infusion to
      assess CO2 production, and immediately thereafter, a 3-hour (13)C-leucine
      infusion to assess leucine appearance rate (Ra), oxidation (Ox), and nonoxidative
      leucine disposal (NOLD), expressed as micromol x kg(-1) x h(-1). Protein
      restriction was associated with a 24% decline in leucine Ra (223 +/- 16 v 298 +/-
      17; P <.01), an index of whole body proteolysis, and a 29% decline in NOLD (180
      +/- 15 v 223 +/- 13; P <.01), an index of whole body protein synthesis. In the
      protein-restricted group, dexamethasone treatment was associated with a 32%
      increase in Ra, (295 +/- 28 v 223 +/- 16; P <.05), a 186% increase in Ox (120 +/-
      14 v 43 +/- 4; P <.001), with no change in NOLD, when compared with the protein
      restricted alone. After protein restriction + dexamethasone, glutamine infusion
      induced a 40% increase in plasma glutamine (1,090 +/- 70 v 780 +/- 29 micromol x
      L(-1); P <.01), but failed to alter Ra, Ox, or NOLD. These results suggest that
      (1) in dogs, protein restriction combined with a 7-day course of dexamethasone
      results in alterations in leucine kinetics similar to those observed in stress
      induced protein wasting in humans, and (2) in that model, a 7-hour IV glutamine
      infusion in the fasting state does not significantly attenuate protein wasting.

PMID- 11230782
TI  - Rate of change in adiposity and its relationship to concomitant changes in
      cardiovascular risk variables among biracial (black-white) children and young
      adults: The Bogalusa Heart Study.
AB  - To assess the annual rate of change in adiposity and its relationship to
      concomitant changes in cardiovascular risk variables during childhood and young
      adulthood, serial data on black and white children (n = 3,459; initial and follow
      up mean age, 8.1 and 14.4 years) and young adults (n = 1,263; initial and follow
      up mean age, 22.5 and 30.9 years) enrolled in the Bogalusa Heart Study were
      examined. Body mass index (BMI) and sum of subscapular and triceps skinfolds were
      used as indicators of adiposity. In addition, measurements were made of systolic
      and diastolic blood pressure and fasting levels of low-density lipoprotein (LDL)
      cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, insulin,
      and glucose. Annualized rate of change for each variable was estimated. The rate
      of increase in adiposity was significantly more pronounced during childhood
      versus adulthood. Race difference (blacks > whites) in the rate of increase in
      adiposity was seen only among females. Females, black females in particular,
      displayed greater rate of increase in adiposity than males. In a multivariate
      analysis, the rate of increase in adiposity was related independently of baseline
      age and baseline adiposity to adverse changes in measured cardiovascular risk
      variables, except glucose. Many of these associations were modulated
      significantly by race, sex, and age group. The impact was relatively greater for
      blood pressure and LDL cholesterol in adults and for triglycerides in children.
      The changes in blood pressure, LDL cholesterol, and HDL cholesterol were greater
      in whites, while the rate of increase in insulin was greater in blacks. Females
      displayed greater changes in blood pressure, HDL cholesterol, and insulin. On the
      other hand, the rate of increase in triglycerides was greater in males. These
      results indicate that increases in adiposity regardless of initial status of body
      fatness alter cardiovascular risk variables towards increased risk beginning in
      childhood, and that this deleterious trend underscores the importance of weight
      control early in life.

PMID- 11230783
TI  - N(G)-monomethyl-L-arginine alters insulin-mediated calf blood flow but not
      glucose disposal in the elderly.
AB  - It has been proposed that an important component of glucose disposal is insulin
      mediated vasodilation via a nitric oxide (NO)-dependent mechanism. Normal aging
      is characterized by a resistance to insulin-mediated glucose disposal and
      deficient endothelial NO production. Impairment of insulin-mediated vasodilation
      could contribute to this insulin resistance. We tested the hypothesis that the NO
      synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) would decrease insulin
      mediated calf vasodilation and whole-body glucose disposal in young subjects but
      would have little or no effect in the elderly. Experiments were performed on
      healthy young (n = 10) and old (n = 10) subjects on 2 study days. Insulin was
      infused for 4 hours at 40 mU/m(2)/min (young) and 34 mU/m(2)/min (old) during
      both studies, and L-NMMA (0.1 mg/kg/min) was coinfused during the last 2 hours of
      insulin on one of these sessions. Calf blood flow was measured by venous
      occlusion plethysmography, and calf vascular conductance was derived from calf
      blood flow and mean arterial blood pressure (MABP). L-NMMA increased whole-body
      insulin-mediated glucose uptake (IMGU) in young subjects (from 11.22 +/- 0.08 to
      12.22 +/- 0.87 mg/kg/min, P <.05) but decreased calf blood flow (from 6.53 +/-
      0.62 to 5.49 +/- 0.43 mL/100 mL/min, P <.05). In contrast, L-NMMA had no effect
      on IMGU in elderly subjects (control v L-NMMA, 7.58 +/- 0.46 v 7.86 +/- 0.37
      mg/kg/min, P = nonsignificant) but increased calf blood flow (from 3.65 +/- 0.36
      to 4.50 +/- 0.32 mL/100 mL/min, P <.01). L-NMMA decreased calf vascular
      conductance in young subjects (from 0.083 +/- 0.008 to 0.064 +/- 0.005 mL/100
      mL/min/mm Hg, P <.05) but not in the elderly (control v L-NMMA, 0.038 +/- 0.004 v
      0.040 +/- 0.002 mL/100 mL/min/mm Hg), consistent with the concept that skeletal
      muscle endothelial NO production is reduced with age. We therefore conclude that
      (1) L-NMMA has different or opposite actions on calf blood flow and IMGU in both
      age groups, indicating that the effect of insulin on skeletal muscle blood flow
      is independent of its influence on glucose disposal in young and old, and (2)
      skeletal muscle NO production decreases with age.

PMID- 11230784
TI  - Lipids, apoprotein B, and associated coronary risk factors in urban and rural
      older Mexican populations.
AB  - The objective of this comparative cross-sectional study was to determine the
      prevalence of dyslipidemias and examine its association with food intake and
      metabolic variables in urban and rural elder Mexican populations. Three different
      communities (urban areas of medium and low income and a rural area) were studied.
      A total of 344 subjects aged 60 years and older and 273 aged 35 to 59 years were
      included. The evaluated parameters were personal medical data, 24-hour diet
      recall, and fasting plasma lipids, insulin, and glucose levels. Older subjects,
      especially men, living in the rural area had lower cholesterol levels (5.02 +/-
      0.97 v 5.6 +/- 1.07 mmol/L; P <.05) and insulin levels (12 +/- 10 v 42 +/- 68
      mU/mL) and higher high-density lipoprotein cholesterol concentrations (1.31 +/-
      0.36 v 1.07 +/-0.28 mmol/L) than the elders from the urban medium-income group.
      Possible explanations for these differences are found in the dietary habits of
      the groups. Rural elders had higher amounts of fiber (20 +/- 11 v 10 +/- 6 g/d)
      and carbohydrate (70% +/- 0.08% v 52% +/- 0.11% of calories) and lower fat (18%
      +/- 0.07% v 33% +/- 0.1% of calories) in their diets. In the urban groups, low
      density lipoprotein hypercholesterolemia was present in 17.8% of adult and 39.1%
      of elderly women (P =.00001). In conclusion, environmental factors still play a
      prominent role in the pathophysiology of the dyslipidemias in the elderly.

PMID- 11230785
TI  - Hormone-replacement therapy increases serum paraoxonase arylesterase activity in
      diabetic postmenopausal women.
AB  - The paraoxonase (PON1) enzyme is associated with high-density lipoproteins (HDL)
      in the blood and is low in patients with type 2 diabetes. Hormone-replacement
      therapy (HRT) can increase HDL cholesterol levels, but its effect on serum PON1
      arylesterase activity is uncertain. The aim of the present study was to determine
      the effect of 6 months' HRT with conjugated equine estrogen and
      medroxyprogesterone acetate on serum PON1 arylesterase activity in postmenopausal
      women with type 2 diabetes. Serum PON1 activity was measured immediately before
      and at the end of the second arm of a randomized, placebo-controlled, crossover
      with washout study originally designed to test the effect of HRT on plasma lipids
      in diabetic postmenopausal women. Baseline serum PON1 arylesterase activity was
      significantly (P <.001) lower in the postmenopausal diabetic women (149 +/- 38
      micromol/mL/min; n = 47) than values in healthy postmenopausal women (173 +/- 32
      micromol/mL/min; n = 51). Serum PON1 activity increased (10%) significantly (P
      =.009) in diabetic women treated with HRT compared with placebo. A significant (P
      =.02) interaction between baseline PON1 activity and treatment indicated a
      greater increase in PON1 activity during HRT in women with lower baseline
      activities. At baseline, serum PON1 arylesterase activity was correlated
      significantly with plasma HDL cholesterol levels in diabetic women (r = 0.333, P
      =.01, n = 47), and the increase in serum PON1 activity was correlated
      significantly with the change in plasma HDL cholesterol during HRT (r = 0.659, P
      =.0001, n = 28). These data suggest that serum PON1 activity is abnormally low in
      postmenopausal women with type 2 diabetes and increases during HRT, particularly
      in women with lower baseline levels and in those who show a concomitant increase
      in HDL cholesterol.

PMID- 11230786
TI  - Overweight is associated with lower serum leptin in Peruvian Indian than in
      Caucasian women: A dissociation contributing to low blood pressure?
AB  - We tested whether plasma levels of leptin and insulin are associated with the
      lower blood pressure in women of Peruvian Indian heritage compared with Caucasian
      women. A total of 181 women from Peru and 85 from Sweden, aged 20 to 60 years,
      with normal plasma glucose levels participated in the study. Measurements of
      anthropometry, blood pressure, and blood tests were performed after overnight
      fasting. Compared with women from Umea in Sweden, women from Lima, Peru had
      higher body mass index (BMI) (26.2 +/- 4.9 v 24.4 +/- 3.8 kg/m(2)), waist
      circumference (85 +/- 11 v 79 +/- 10 cm), lower systolic blood pressure (99 +/-
      15 v 114 +/- 14 mm; P <.001) and diastolic blood pressure (67 +/- 7 v 74 +/- 10
      mm; P <.001). In addition, they had a reduction of the ratio of plasma leptin to
      BMI (0.52 +/- 0.22 v 0.61 +/- 0.36; P <.001), greater plasma insulin (80 +/- 42 v
      41 +/- 21 pmol/L), but lower plasma glucose (4.2 +/- 0.5 v 5.1 +/- 0.5 mmol/L; P
      <.001). Furthermore, the 181 women from Lima had higher plasma triglyceride
      levels (1.5 +/- 0.8 v 1.3 +/- 0.7; P =.039), but lower plasma high-density
      lipoprotein (HDL)-cholesterol (1.0 +/- 0.2 v 1.5 +/- 0.4 mmol/L; P <.001) and
      total plasma cholesterol (5.0 +/- 1.1 v 5.9 +/- 1.3 mmol/L; P <.001) levels.
      Plasma leptin correlated with blood pressure and BMI in both populations (P
      <.001). In multiple regression analysis, BMI, but not log leptin, emerged as the
      determinant for systolic blood pressure. We concluded that women living in Lima
      have significant lower blood pressure levels in association with elevated plasma
      insulin concentrations, but lower plasma leptin values adjusted for BMI in
      comparison with women from northern Sweden. This may suggest that the concept of
      metabolic syndrome is different among women with Peruvian Indian heritage in
      comparison to a Caucasian population.

PMID- 11230787
TI  - Postprandial lipemia and associated metabolic disturbances in healthy and
      hyperlipemic postmenopausal women.
AB  - The increased risk for coronary artery disease observed in postmenopausal women
      is partly explained by a more atherogenic fasting lipoprotein profile. Moreover,
      natural menopause has been associated with an altered postprandial lipid profile.
      To better characterize the interaction between fasting and postprandial lipid
      profile after menopause, we examined postprandial changes in several lipid
      parameters in three age-matched groups of postmenopausal women (16 affected by
      mixed hyperlipemia, 17 by common hypercholesterolemia, and 17 normolipemic), who
      underwent a standardized oral fat-loading test. The magnitude of postprandial
      lipemia, expressed as 8-hour triglyceride incremental area under the curve, was
      greater in women with mixed hyperlipemia (1,326 +/- 372 mg x dL(-1) x h(-1)) than
      in normal (484 +/- 384 mg x dL(-1) x h(-1)) and hypercholesterolemic (473 +/- 223
      mg x dL(-1) x h(-1); both P <.0001) women, and the differences held after
      adjustment for body mass index and fasting insulin. Women with mixed hyperlipemia
      showed a significant postprandial decrease in high-density lipoprotein 2 (HDL(2))
      cholesterol, lipoprotein (a), and low-density lipoprotein (LDL) particle size.
      Both hypercholesterolemic and normolipemic women showed a significant
      postprandial decrease in HDL cholesterol and lipoprotein (a) levels but not in
      LDL size. In a multiple linear regression analysis, fasting triglyceride levels,
      insulin level, and waist-hip ratio were all independent predictors of the
      magnitude of postprandial lipemia. In conclusion, postmenopausal women with mixed
      hyperlipemia show a greater postprandial triglyceride increase and a more
      pronounced reduction in HDL cholesterol level and LDL size than
      hypercholesterolemic and normolipemic subjects. The presence of the features of
      insulin resistance syndrome could contribute to the deterioration of postprandial
      lipemic response in these subjects.

PMID- 11230788
TI  - Energy expenditure following oral glucose load in ten uremic patients before and
      after three months on a ketoacid-supplemented very-low-protein diet.
AB  - We have previously shown that a ketoacid-supplemented very-low-protein diet
      (KSVLPD), which has been proposed to slow down the rate of progression of chronic
      renal failure (CRF), improves tissue insulin sensitivity and decreases
      hyperinsulinemia in predialytic uremic patients. However, this diet may interfere
      with nutritional status. The aim of this study was to study basal energy
      expenditure (EE) and EE after an oral glucose load in patients with CRF before
      and during a KSVLPD (0.3 cal x kg wt(-1) x d(-1) supplemented with aminoacid and
      ketoanalogs) using oral glucose loading in combination with indirect calorimetry.
      We also monitored body weight and analyzed body composition by dual-energy x-ray
      (DEXA) during KSVLPD. In the third month of KSVLPD, no significant change in
      total body weight was observed, but DEXA showed a decrease in lean tissue mass
      (LTM; 46.2 +/- 3.6 kg before v 44 +/- 3.4 kg in the third month; P <.01) and an
      increase in body fat mass (20.1 +/- 2.4 kg before v 21.3 +/- 2.4 kg on KSVLPD; P
      <.05). Postabsorptive plasma glucose level was significantly lower, and glucose
      oxidation and energy expenditure per LTM were significantly increased (EE, 20 +/-
      0.8 cal x kg LTM(-1) x min(-1) before diet v 21.9 +/- 1.1 cal x kg LTM(-1) x min(
      1) after 3 months on KSVLPD; P <.01). Plasma glucose and serum insulin levels
      were significantly lower after glucose loading, and glucose oxidation increased.
      EE values were significantly higher after the oral glucose load, and cumulative
      EE after oral load increased from 20.7 +/- 0.7 cal x kg LTM(-1) x min(-1) before
      the diet to 22.9 +/- 1.1 cal x kg LTM(-1) x min(-1) in the third month of KSVLPD;
      P <.001). Glucose oxidation was higher and cumulative glucose storage was
      decreased after diet (29.6 +/- 4.2 g v 20.9 +/- 3.4 g on KSVLPD; P <.01). We
      conclude that KSVLPD increases EE in the postabsorptive state and after an oral
      glucose load with an adaptation of lean tissue mass in the third month of the
      diet. Therefore, during KSVLPD, strict monitoring of dietetic management is
      necessary to maintain energy requirements at high levels appropriate to the new
      EE.

PMID- 11230789
TI  - Glucose loading during primary culture has opposite effects on the viability of
      hepatocytes exposed to potassium cyanide and to iodoacetic acid.
AB  - Whether or not to apply nutritional pretreatment and how to do so are
      controversial issues with respect to the liver about to undergo aggressive
      intervention. We studied the effects of glucose loading on the viability of
      hepatocytes that were subsequently exposed to the inhibitors of carbohydrate
      metabolism, potassium cyanide (KCN) and iodoacetic acid (IAA). After rat
      hepatocytes were cultured for 24 hours in Leibovitz's L-15 medium containing 0,
      10, 20, and 30 mmol/L glucose, the medium was replaced with modified Hanks-HEPES
      buffer with or without 2.5 mmol/L KCN or 0.5 mmol/L IAA. Lactate dehydrogenase
      (LDH) activity, lactate concentration, and pH of the supernatant were measured
      after 0, 2, 4, and 6 hours of exposure to KCN and after 0, 20, 40, and 60 minutes
      of exposure to IAA. Glycogen and adenosine triphosphate (ATP) contents in the
      hepatocytes were measured simultaneously. Hepatocytes cultured with various
      concentrations of glucose for 24 hours stored levels of glycogen in proportion to
      the glucose concentration in the culture medium without any significant
      difference in viability. The hepatocytes cultured with higher glucose
      concentrations maintained a higher ATP content and released less LDH and more
      lactate, and the pH decreased in the supernatant during exposure to KCN.
      Conversely, hepatocytes cultured with lower glucose concentrations maintained a
      higher ATP content and released less LDH during exposure to IAA. In conclusion,
      prior glucose loading appears to be beneficial for hepatocytes if oxidative
      phosphorylation is to be inhibited, whereas withholding glucose appears to be
      beneficial if glycolysis is to be inhibited.

PMID- 11230790
TI  - Insulin and non-insulin-dependent glucose disposal in middle-aged and young
      athletes versus sedentary men.
AB  - The purpose of this study was to delineate the respective roles of aging and
      endurance training on glucose disposal. Thirty-two subjects (16 middle-aged men:
      8 cyclists [MAcy], and 8 sedentary men [MAsed] and 16 young men: 8 cyclists [Ycy]
      and 8 sedentary men [Ysed]) were compared in this study. After overnight fasting,
      glucose was administered intravenously (0.5 g. kg(-1), 30% solution) and insulin
      glucose interactions were assessed by measuring indices of insulin sensitivity
      (SI) and glucose effectiveness (Sg) using Bergman's minimal model. Sg includes
      basal insulin effectiveness (BIE) and glucose effectiveness at zero insulin
      (GEZI). Endurance training improved SI and Sg in all subjects, regardless of age
      (P <.05), but an increase in GEZI was found only in young men (P <.05). An effect
      of aging was found in sedentary subjects, who exhibited a lower SI (P <.05) when
      older. However, this effect disappeared with training, in which SI was nearly
      identical in young and middle-aged subjects. There was a correlation between SI
      and &Vdot;omicron(2max) in middle-aged men (r =.76, P <.01). These data suggest
      that the higher glucose uptake in endurance-trained male cyclists was mostly
      attributable to an increase in non-insulin-dependent glucose uptake in the young
      men and to an increase in its insulin-dependent component in the middle-aged men.

PMID- 11230792
TI  - Interaction of estrogen replacement therapy with the thrombophilic 20210 G/A
      prothrombin gene mutation for atherothrombotic vascular disease: a cross
      sectional study of 275 hyperlipidemic women.
AB  - In a consecutive case series, cross-sectional study of 275 women referred for
      therapy of hyperlipidemia, (75 [27%] on estrogen replacement therapy [ERT]), our
      specific aim was to determine whether ERT-mediated thrombophilia and
      heterozygosity for the thrombophilic 20210 G/A prothrombin gene mutation
      interacted as risk factors for atherothrombotic cardiovascular disease (ATCVD).
      Of the 275 women, 100 (36%) had ATCVD; 10 (3.6%) were heterozygous for the 20210
      G/A prothrombin gene mutation. In women without the 20210 G/A prothrombin gene
      mutation, 15 of 71 (21%) on ERT had ATCVD versus 78 of 194 (40%) not on ERT (X(2)
      = 8.31, P =.004). By stepwise logistic regression, in 261 women with ATCVD risk
      factor data, positive explanatory variables for ATCVD included the 20210 G/A
      prothrombin mutation (risk odds ratio, 5.8; 95% confidence intervals [CI], 1.4 to
      30.2; P =.021) and a 20210 G/A prothrombin gene mutation*ERT interaction term
      (risk odds ratio, 2.70; 95% CI, 1.4 to 5.4; P =.004). ATCVD events were more
      likely in 2 subgroups of women (ERT minus [-] and 20210 G/A prothrombin gene
      mutation -) or (ERT plus [+] and 20210 G/A prothrombin gene mutation +), P =.004.
      Other positive explanatory variables for ATCVD events included age (P =.004),
      triglycerides (P =.012), lipoprotein (a) (P =.03), and homocysteine (P =.032).
      ERT may be protective against ATCVD when the thrombophilic 20210 G/A prothrombin
      gene mutation is absent, whereas the 20210 G/A prothrombin gene mutation may
      increase risk for ATCVD, particularly in the presence of ERT. We suggest that the
      20210 G/A prothrombin gene mutation be measured in all women on ERT or before
      beginning ERT to identify those heterozygous for the thrombophilic prothrombin
      gene mutation (4%) in whom ERT is contraindicated because of increased risk for
      ATCVD and thromboembolism, and a second, much larger group of women without the
      20210 G/A prothrombin gene mutation (96%) in whom ERT may possibly reduce risk
      for ATCVD.

PMID- 11230791
TI  - Simvastatin treatment on postprandial hypertriglyceridemia in type 2 diabetes
      mellitus patients with combined hyperlipidemia.
AB  - Recent studies have shown that statins are effective in reducing fasting low
      density lipoprotein-cholesterol (LDL-C) and triglyceride levels. However, it
      remains unknown if treatment with statins also lowers daily postprandial
      triglyceride concentrations, which may promote atherogenesis in type 2 diabetes
      subjects. Forty-one subjects with type 2 diabetes and combined hyperlipidemia who
      had stable glycemic control were randomly assigned to take simvastatin 20 mg (n =
      27) or a placebo (n = 14) once daily for 12 weeks. The medication dosage was
      doubled after 4 weeks if a subject's LDL-C was not less than 130 mg/dL. Among
      these participants, 24 subjects (15 on simvastatin and 9 on placebo) agreed to
      take a meal tolerance test with isocaloric mixed meals (carbohydrate, 52%; fat,
      33%, and protein, 15% of the daily caloric intake) and daytime hourly blood
      sampling from 8 AM to 4 PM. Simvastatin treatment reduced the fasting total
      cholesterol level from 237 +/- 5 to 178 +/- 6 mg/dL (-25%), the LDL cholesterol
      level from 150 +/- 6 to 87 +/- 5 mg/dL (-40%), and raised high-density
      lipoprotein-cholesterol (HDL-C) level from 36 +/- 2 to 40 +/- 2 mg/dL (+11%) (all
      P <.001). Fasting and daily ambient triglyceride concentrations from 8 AM to 4 PM
      decreased significantly in response to simvastatin administration (P <.001), but
      not to the placebo (P =.305). Simvastatin treatment not only decreased total
      cholesterol and LDL-C levels and increased HDL-C levels effectively, it also
      decreased fasting, as well as daily postprandial triglyceride concentrations, but
      had no effect on glycemic control in type 2 diabetes subjects with combined
      hyperlipidemia.

PMID- 11230793
TI  - Variations in the vitamin D-binding protein (Gc locus) and risk of type 2
      diabetes mellitus in French Caucasians.
AB  - Electrophoretic variants of the vitamin D-binding protein (DBP) have been
      reported to be associated with type 2 diabetes mellitus (DM) or with prediabetic
      phenotypes in several non-Caucasian populations. Two frequent missense
      polymorphisms at codons 416 (Asp --> Glu) and 420 (Thr --> Lys) are the genetic
      basis for the 3 common electrophoretic variants of DBP (Gc1F, Gc1S, and Gc2) and
      the resulting circulating phenotypes (Gc1F/Gc1F, Gc1F/Gc1S, Gc1S/Gc1S, Gc1F/Gc2,
      Gc1S/Gc2, and Gc2/Gc2). In this study, we investigated the association of these
      polymorphisms with type 2 DM in French Caucasian subjects. Variations at codons
      416 and 420 were examined by polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP). Allele frequencies at both codons did not differ
      in type 2 DM patients and in control subjects (Asp416: 42.4% v 46.2%,
      respectively, P =.33; Lys420: 25.5% v 29.0%, respectively, P =.31). Distribution
      of genotypes at both codons, of the haplotypes defined by the 2 codons, and of
      the DBP phenotypes defined by the haplotypes were also similar in diabetic and
      control subjects. In conclusion, our study suggests that genetic variants of the
      DBP gene are not associated with the susceptibility to type 2 DM in French
      Caucasians.

PMID- 11230794
TI  - Distribution and correlates of high-density lipoprotein subclasses among children
      and adolescents.
AB  - Levels of high-density lipoprotein (HDL) cholesterol among children vary by sex
      and race/ethnicity and are correlated with age, obesity, and other
      characteristics. Several studies of adults have indicated that atherogenicity of
      HDL particles may vary by size, but there is little information on the
      distribution and correlates of HDL subfractions in early life. We used nuclear
      magnetic resonance (NMR) spectroscopy to determine the mean HDL particle size and
      levels of 3 HDL subclasses among 10- to 17-year-olds (n = 918). We found the mean
      HDL particle size to be (1) inversely associated with age among boys, (2) larger
      among girls than boys, and (3) larger among black children than among white
      children. These associations with particle size reflected contrasting
      associations with various HDL subclasses; among boys, for example, levels of
      large HDL decreased with age, whereas levels of small HDL remained constant
      (black boys) or tended to increase (white boys). Furthermore, relative weight and
      levels of both triglycerides and low-density lipoprotein (LDL) cholesterol were
      associated inversely with levels of large HDL, but positively with levels of
      small HDL. These contrasting associations suggest that the role of HDLC in
      coronary heart disease (CHD) may be more complex than previously thought, and
      that the analysis of HDL subclasses may improve the accuracy of CHD prediction.

PMID- 11230795
TI  - Regulation of ryanodine receptors by reactive nitrogen species.
AB  - The ryanodine receptors (RyRs) are large intracellular calcium release channels
      that play an important role in the control of the calcium levels in excitable and
      non-excitable cells. Many endogenous modulators such as Mg2+, ATP, or calmodulin
      can affect the channel activities of the three known mammalian RyR isoforms. RyRs
      also are known to be redox-responsive. However, the molecular basis and the
      physiological relevance of redox modulation of RyRs are unclear. Recent evidence
      suggests that nitric oxide (NO) and related molecules may be endogenous
      regulators of the skeletal and cardiac muscle RyRs. The two tissues express
      nitric oxide synthases (NOSs), and NO or NO-related species have been shown to
      affect Ca2+ release channel activities directly via covalent modifications of
      thiol groups. Both an oxidative and a nitrosative modification of RyRs have been
      described, leading to either a reversible or irreversible alteration of RyR ion
      channel activity. Additional mechanisms of regulation may include cyclic GMP
      dependent signaling pathways and NO modification of RyR regulatory proteins such
      as the surface membrane L-type Ca2+ channel. Modification of RyRs by NO may
      influence a variety of physiological functions such as insulin release, vasomotor
      control, and muscle contraction.

PMID- 11230796
TI  - Effect of N8-acetylspermidine deacetylase inhibition on the growth of L1210
      cells.
AB  - A selective inhibitor of N8-acetylspermidine deacetylase has been employed to
      study the role of N8-acetylspermidine deacetylation in the regulation of L1210
      cell growth. This inhibitor, 7-[N-(3-aminopropyl) amino] heptan-2-one (APAH), was
      found to stimulate the growth of L1210 cells at concentrations between 10 microM
      and 0.5 mM. Maximum stimulation was seen at 100 microM, resulting in
      significantly increased rates of cell division and maximum cell density. N8
      Acetylspermidine levels in L1210 cells were shown to increase significantly after
      the APAH treatment as would be expected for deacetylase inhibition. The effects
      of deacetylase inhibition were mimicked by addition of N8-acetylspermidine to the
      culture medium at concentrations greater than 1 mM as indicated by a subsequent
      increase in rate of cell growth and maximum cell density. The magnitudes of the
      increases in growth observed were not large, but this might be expected in cells
      that are already in a rapid growth phase. Other exogenously added polyamines
      including N1-acetylspermidine, spermidine, putrescine, and spermine did not
      stimulate cell growth. These data suggest that stimulation of cell growth occurs
      as a consequence of N8-acetylspermidine accumulation and N8-acetylspermidine
      deacetylase inhibition.

PMID- 11230797
TI  - Decreased thymosin beta4 in apoptosis induced by a variety of antitumor drugs.
AB  - As many antitumor drugs can kill tumors through the induction of apoptosis, the
      effect of these drugs presumably would be enhanced if they were used in
      combination with other drugs that interact with apoptotic processes. To clarify
      the biological events involved in the induction of apoptosis, we examined changes
      in the proteins associated with induction of apoptosis by antitumor drugs. When
      Molt-4 cells were exposed to the antitumor drugs etoposide, meso-2,3-bis(3,5
      dioxopiperazine-1-yl)butane (ICRF-193), and neocarzinostatin, they exhibited
      apoptotic cell death as determined by flow cytometry using fluorescein
      isothiocyanate (FITC)-labeled annexin V staining of phosphatidylserine on
      membranes and detection of hypodiploid cells. Following the induction of
      apoptosis, a low molecular weight protein that was identified to be thymosin
      beta4 by HPLC analysis was commonly decreased, and the morphology of actin
      filaments changed into clump formations. These results suggest that decreased
      thymosin beta4 is involved in the induction of apoptosis by antitumor drugs.

PMID- 11230798
TI  - Chlorpromazine and human platelet glycerolipid metabolism: precursor specificity
      and significance of drug-platelet interaction time.
AB  - Chlorpromazine is known to have a number of effects on glycerolipid metabolism in
      a variety of cell types, and in some cases reports are contradictory. To
      investigate the basis for some of these discrepancies, we reinvestigated the
      effects of chlorpromazine on some aspects of platelet glycerolipid metabolism.
      Time-courses conducted with [3H]glycerol or [3H]palmitic acid showed that the
      effects of chlorpromazine on the labelling of phosphatidylcholine,
      diacylglycerol, and triacyglycerol were highly dependent upon platelet-drug
      interaction time. The time-dependent changes in labelling patterns were
      independent of the presence of radiolabel during incubation, and were not the
      results of time-dependent changes in the platelets per se. The effects of
      chlorpromazine on the labelling of platelet glycerolipids by [3H]glycerol,
      [3H]palmitic acid, [32P]P(i) ([32P]phosphatase), and [14C]choline were compared.
      Dose-response curves conducted at 30-min incubation time showed that
      chlorpromazine potently inhibited labelling of diacylglycerol and diacyglycerol
      derived lipids (triacyglycerol and phosphatidylcholine) by the 3H-labelled
      precursors. Labelling of phosphatidylcholine by [32P]P(i) or [14C]choline was,
      however, not affected at all by the drug. We conclude that the effects of
      chlorpromazine on platelets are highly time-dependent, and that the prolonged
      effects are most likely to be of biological significance. Furthermore, in
      platelets the effects of the drug on the labelling of phosphatidylcholine by
      isotope-labelled precursors are highly dependent on the route of incorporation of
      the specific precursor chosen.

PMID- 11230799
TI  - Angiotensin II receptor internalization and signaling in isolated rat
      hepatocytes.
AB  - Since angiotensin II (Ang II)-induced receptor internalization is required to
      maintain the production of certain intracellular signals in some target cells, we
      investigated the relationships between Ang II receptor endocytosis and the
      generation of second messengers in rat hepatocytes. The results of the present
      study demonstrate that in response to exposure of hepatocytes to Ang II, a
      decrease in surface Ang II receptors occurred, consistent with a rapid
      endocytosis of the receptor-bound hormone complex. Pretreatment of cells with
      okadaic acid (OA) did not have any effect on receptor-mediated internalization.
      In contrast, a marked reduction of the Ang II receptor endocytosis process
      occurred after treatment of hepatocytes with phenylarsine oxide (PAO), indicating
      that cysteine residues could be involved in receptor-mediated endocytosis.
      Stimulation of cells with Ang II blocked the generation of cyclic adenosine
      monophosphate (cAMP), which follows the stimulation of hepatocytes with
      forskolin. Moreover, Ang II increased both inositol 4,5-bisphosphate (IP2) and
      inositol 1,4,5-trisphosphate (IP3) generation, and enhanced intracellular calcium
      concentration ([Ca2+]i). Exposure of cells to PAO did not alter the effect of Ang
      II on the accumulation of cAMP after forskolin stimulation, indicating that
      endocytosis of the agonist-receptor complex is not involved in adenylate cyclase
      inhibition. Conversely, PAO and OA markedly reduced IP2 and IP3 synthesis, and
      the plateau phase of Ang II-induced Ca2+ mobilization. The relationship between
      Ang II-induced endocytosis and the generation of phosphoinositols and increment
      in [Ca2+]i indicates that sequestration of the Ang II receptor is necessary to
      maintain the production of these intracellular signals in rat hepatocytes.

PMID- 11230800
TI  - Configurational requirements of the sugar moiety for the pharmacological activity
      of anthracycline disaccharides.
AB  - The amino sugar is recognized to be a critical determinant of the activity of
      anthracycline monosaccharides related to doxorubicin and daunorubicin. In an
      attempt to improve the pharmacological properties of such agents, novel
      anthracycline disaccharides have been designed in which the amino sugar,
      daunosamine, is separated from the aglycone by another carbohydrate moiety. In
      the present study, we examined the influence of the orientation of the second
      sugar residue on drug biochemical and biological properties in a series of
      closely related analogs. This structure-activity relationship study showed that
      the substitution of the daunosamine for the disaccharide moiety dramatically
      reduced the cytotoxic potency of the drug in the 4-methoxy series (daunorubicin
      analogs). In contrast, in the 4-demethoxy series (idarubicin analogs), the C-4
      axial, but not the equatorial, configuration conferred a cytotoxic potency and
      antitumor activity comparable to that of doxorubicin. The configuration also
      influenced the drug's ability to stimulate topoisomerase II alpha-mediated DNA
      cleavage. Indeed, the glycosides with the equatorial orientation were ineffective
      as topoisomerase II poisons, whereas the compounds with axial orientation were
      active, although the daunorubicin analog exhibited a lower activity than the
      idarubicin analog. It is conceivable that the axial orientation allows an optimal
      interaction of the drug with the DNA-enzyme complex only in the absence of the
      methoxy group. Our results are consistent with a critical role of the sugar
      moiety in drug interaction with the target enzyme in the ternary complex.

PMID- 11230801
TI  - Topoisomerase II inhibition by aporphine alkaloids.
AB  - The aporphine alkaloids (+)-dicentrine and (+)-bulbocapnine are non-planar
      molecules lacking features normally associated with DNA binding by intercalation
      or minor groove binding. Surprisingly, dicentrine showed significant activity as
      a topoisomerase II (EC 5.99.1.3) inhibitor and also was active in a DNA unwinding
      assay. The DNA unwinding suggests DNA intercalation, which could explain the
      inhibition of topoisomerase II. Bulbocapnine, which differs from dicentrine only
      by the presence of a hydroxyl group at position 11 and the absence of a methoxyl
      group at position 9, was inactive in all assays. Molecular modeling showed that
      dicentrine can attain a relatively planar conformation, whereas bulbocapnine
      cannot, due to steric interaction between the 11-hydroxyl group and an oxygen of
      the methylenedioxy ring. These observations suggest that dicentrine is an
      "adaptive" DNA intercalator, which can bind DNA only by adopting a somewhat
      strained planar conformation. The requirement of a suboptimal conformation to
      achieve DNA binding appears to make dicentrine a weaker topoisomerase II
      inhibitor than the very planar oxoaporphine alkaloid liriodenine. These results
      suggest that it may be possible to modulate DNA binding and biologic activity of
      drugs by modifications affecting their ability to adopt planar conformations.

PMID- 11230802
TI  - HIV protease inhibitor ritonavir: a more potent inhibitor of P-glycoprotein than
      the cyclosporine analog SDZ PSC 833.
AB  - The effect of P-glycoprotein inhibition on the uptake of the HIV type 1 protease
      inhibitor saquinavir into brain capillary endothelial cells was studied using
      porcine primary brain capillary endothelial cell monolayers as an in vitro test
      system. As confirmed by polymerase chain reaction and Western blot analysis, this
      system functionally expressed class I P-glycoprotein (pgp1A). P-Glycoprotein
      isoforms pgp1B or pgp1D could not be detected. The uptake of saquinavir into
      endothelial cells could be described as the result of a diffusional term of
      uptake and an oppositely directed saturable extrusion process. Net uptake of
      saquinavir into cultured brain endothelial cells could be increased significantly
      up to 2-fold by SDZ PSC 833 in a dose-dependent manner, with an IC(50) of 1.13
      microM. In addition, the HIV protease inhibitor ritonavir inhibited p
      glycoprotein-mediated extrusion of saquinavir with an IC(50) of 0.2 microM,
      indicating a high affinity of ritonavir for p-glycoprotein. In conclusion, we
      showed that the HIV protease inhibitor ritonavir is a more potent inhibitor of P
      glycoprotein than the multidrug resistance (MDR)-reversing agent SDZ PSC 833. The
      inclusion of this drug in combination regimens may greatly facilitate brain
      uptake of HIV protease inhibitors, which is especially important in patients
      suffering from AIDS dementia complex.

PMID- 11230803
TI  - Effects of a water-soluble antitumor ether phosphonoinositide, D-myo-inositol 4
      (hexadecyloxy)-3(S)-methoxybutanephosphonate (C4-PI), on inositol lipid
      metabolism in breast epithelial cancer cell lines.
AB  - We have demonstrated previously that D-myo-inositol 4-(hexadecyloxy)-3(S)
      methoxybutanephosphonate (C4-PI), an isosteric phosphonate analog of
      phosphatidylinositol developed to inhibit inositol lipid metabolism, was unable
      to inhibit phosphatidylinositol (PI) 3-kinase activity. We now report the effects
      of the compound on other aspects of inositol metabolism. We demonstrated that C4
      PI inhibits the activity of purified recombinant PI-phospholipase C-beta (PLC
      beta) at all concentrations tested; it enhanced the activity of PI-PLC-gamma and
      PI-PLC-delta at low concentrations (10 microM), while severely inhibiting their
      activities at higher concentrations. In the breast cancer cell lines MCF-7
      (estrogen receptor positive) and MDA-MB-468 (estrogen receptor negative), C4-PI
      had no effect on the uptake of D-myo-inositol but severely inhibited its
      incorporation into PI. In spite of the drastic decrease in PI synthesis, C4-PI
      did not affect the levels of inositol incorporated into phosphatidylinositol 4,5
      bisphosphate (PIP2) in the cells. In vitro assays showed that C4-PI inhibited PI
      synthase activity (inhibition of 35% at 50 microM) but had little effect on PI 4
      kinase activity (inhibition of 13% at 150 microM). C4-PI inhibited the
      proliferation of MCF-7 and MDA-MB-468 cell lines with IC(50) values of 12 and 18
      microM. Taken together, the results suggest that the accumulation of [3H]inositol
      in PIP2 in cells incubated with C4-PI may be due to the inhibition of PIP2
      hydrolysis in the cells with no effect on its synthesis. The role of these C4-PI
      induced effects in the mechanism of growth inhibition by C4-PI remains to be
      established.

PMID- 11230804
TI  - Inhibition of human pancreatic islet insulin release by receptor-selective
      somatostatin analogs directed to somatostatin receptor subtype 5.
AB  - Somatostatin (SS)-14 and SS28 are produced by pancreatic D cells and gut mucosa
      and inhibit pancreatic islet insulin and glucagon release. There are five
      distinct SS receptor (SSTR) subtypes, namely SSTR1-5, which show different
      affinities for SS14 and SS28. In order to identify the subtype responsible for
      inhibition of insulin release by human B cells, SSTR-selective SS analogs were
      tested in isolated human islets. Glucose-stimulated insulin secretion in human
      islets incubated for 1 hr at 20 mM glucose, and in islets cultured for 24 hr at a
      near-physiological (6.1 mM) glucose concentration, was inhibited (<50% of the
      control) by SSTR5-specific analogs and by SS14 and SS28. SS14, SS28, and
      different SSTR5 preferential analogs also inhibited islet amyloid polypeptide
      release during the 24-hr culture. On the other hand, a group of SSTR2-selective
      analogs failed to inhibit insulin release. Analysis by reverse transcription
      polymerase chain reaction indicated that human islets express similar amounts of
      SSTR2 and SSTR5 mRNAs, while human pancreatic ductal cells express much lower
      levels of these mRNAs. In conclusion, our data suggest that SSTR5 is an important
      mediator of the insulin inhibitory action of SS in cultured human islets.

PMID- 11230805
TI  - Tissue-specific regulation of glutathione homeostasis and the activator protein-1
      (AP-1) response in the rat conceptus.
AB  - Oxidative stress in the conceptus is characterized by an increased oxidized to
      reduced glutathione (GSSG:GSH) ratio and the induction of fos and jun mRNAs,
      transcripts for components of the activator protein-1 (AP-1) transcription
      factor. We investigated the role of glutathione homeostasis in the rat conceptus
      in the regulation of: (1) AP-1 expression and activity, and (2) the activities of
      glutathione-dependent cytoprotective enzymes. Glutathione content was enhanced
      with the addition of l-2-oxothiazolidine-4-carboxylate (OTC), a precursor of
      cysteine, a rate-limiting substrate in glutathione biosynthesis. Day 10 rat
      conceptuses were cultured for 44 hr with 0, 5, 10, or 20 mM OTC. High
      concentrations (10 and 20 mM) of OTC were embryotoxic. Incubation of the
      conceptus in 5 mM OTC caused mild (not statistically significant) embryotoxicity,
      increased significantly the embryonic glutathione content, prevented culture
      induced oxidative stress, and inhibited the induction of AP-1 transcripts and DNA
      binding activity in the embryo. In contrast, in the yolk sac, 5 mM OTC failed to
      increase glutathione content or to prevent oxidative stress or AP-1 induction.
      Thus, regulation of glutathione status in the conceptus is tissue-specific.
      Glutathione S-transferase and glutathione peroxidase activities were increased
      approximately 50% in cultured embryos and yolk sacs. OTC treatment (5 mM)
      prevented this induction in the embryo, but not in the yolk sac, suggesting a
      role for glutathione homeostasis in the regulation of these enzymes. Tissue
      specific regulation of glutathione status and of cytoprotective enzymes in the
      conceptus during organogenesis may impact on the consequences of insult with
      oxidative stress.

PMID- 11230806
TI  - Functional analysis of activation and repression domains of the rainbow trout
      aryl hydrocarbon receptor nuclear translocator (rtARNT) protein isoforms.
AB  - The aryl hydrocarbon receptor nuclear translocator (ARNT) protein is involved in
      many signaling pathways. Rainbow trout express isoforms of ARNT protein that are
      divergent in their C-terminal domains due to alternative RNA splicing. Rainbow
      trout ARNT(b) (rtARNT(b)) contains a C-terminal domain rich in glutamine and
      asparagine (QN), whereas the C-terminal domain of rtARNT(a) is rich in proline,
      serine, and threonine (PST). rtARNT(b) functions positively in AH receptor
      mediated signaling, whereas rtARNT(a) functions negatively. Studies were
      performed to understand how changes in the C-terminal domains of the two rtARNT
      isoforms affect function. Deletion of the QN-rich C-terminal domain of rtARNT(b)
      did not affect function in aryl hydrocarbon receptor (AHR)-mediated signaling,
      whereas deletion of the PST-rich domain of rtARNT(a) restored function.
      Expression of the PST-rich domain on truncated rtARNT(b) or mouse ARNT (mARNT)
      reduced function of this protein by 50-80%. Gel shift assays revealed that the
      PST-rich domain affected AHR-mediated signaling by inhibiting DNA binding of the
      AHR*ARNT heterodimer. Gal4 transactivation assays revealed a potent
      transactivation domain in the QN-rich domain of rtARNT(b). In contrast, Gal4
      proteins containing the PST-rich domain of rtARNT(a) did not transactivate
      because the proteins did not bind to DNA. Secondary structure analysis of the PST
      rich domain revealed hydrophilic and hydrophobic regions. Truncation of the
      hydrophobic domain that spanned the final 20-40 amino acids of the rtARNT(a)
      restored function to the protein, suggesting that repressor function was related
      to protein misfolding or masking of the basic DNA binding domain. Functional
      diversity within the C-terminal domain is consistent with other negatively acting
      transcription factors and illustrates a common biological theme.

PMID- 11230807
TI  - Serotonin-induced secretion of von Willebrand factor from human umbilical vein
      endothelial cells via the cyclic AMP-signaling systems independent of increased
      cytoplasmic calcium concentration.
AB  - Endothelial cells are able to synthesize von Willebrand factor (vWf) protein,
      which is then either secreted in a constitutive way or stored within specific
      cellular secretory granules, the Weibel-Palade bodies. Stimulated secretion of
      vWf from these organelles is thought to be induced by agonists causing a
      transient increase in cytoplasmic calcium concentrations. Serotonin (5
      hydroxytryptamine, 5-HT), a local transmitter substance released by activated
      platelets, has also recently been shown to induce the secretion of vWf. In
      experiments with human umbilical vein endothelial cells (HUVEC), we found that
      the 5-HT-induced secretion occurred without a significant increase in cellular
      calcium levels. The 5-HT 1(D) subtype-specific receptor agonist sumatriptan also
      induced the release of vWf without causing a calcium signal in HUVEC. Stimulation
      of endothelial cells with the adenylate cyclase inhibitor, MDL-12 A330, led to
      the secretion of vWf as well. Simultaneous addition of submaximal concentrations
      of histamine and 5-HT to HUVEC potentiated the effects of either agonist.
      Together, these results suggest that in HUVEC 5-HT-induced secretion of vWf is
      mediated by a decrease in cyclic AMP levels and is independent of changes in
      cytoplasmic calcium levels.

PMID- 11230809
TI  - Solution of the nerve cable equation using Chebyshev approximations.
AB  - The propagation of excitation along the dendrites and the axon of a neurone is
      described by a partial differential equation which is nonlinear when voltage
      gated conductances are present. In this case, numerical methods are employed to
      obtain a solution: the evolution of the membrane potential in space and time.
      Even when the membrane is passive (linear), numerical methods might still be
      preferred to analytical ones that are often too cumbersome to obtain. In this
      paper, we present the Chebyshev pseudospectral or collocation method as an
      alternative to the hitherto commonly used finite difference schemes
      (compartmental models) that are based on sufficiently fine equidistant
      subdivisions of the spatial structure (dendrites or axon). In the Chebyshev
      method, solutions are approximated by finite Chebyshev series. The solutions have
      uniform, usually high, numerical accuracy at any spatial point, not only at the
      original collocation points. Often, truncation errors become negligible, hence,
      the total error is essentially the rounding error of the computations.
      Furthermore, quantities involving spatial derivatives, and in particular the
      axial current, can be computed exactly from the solution, i.e. the membrane
      potential. Space-dependent parameter distributions (channel densities, non
      uniform dendritic geometries), as well as mixed linear boundary conditions can
      easily be implemented, and can be chosen from the large class of piecewise smooth
      functions.

PMID- 11230808
TI  - Changes in the generation of reactive oxygen species and in mitochondrial
      membrane potential during apoptosis induced by the antidepressants imipramine,
      clomipramine, and citalopram and the effects on these changes by Bcl-2 and Bcl
      X(L).
AB  - In order to investigate the molecular mechanism of the antineoplastic effects
      exerted by the antidepressive agents imipramine, clomipramine, and citalopram, we
      examined the effects of these compounds on cell viability, generation of reactive
      oxygen species (ROS), and mitochondrial membrane potential (DeltaPsi(m)) in human
      acute myeloid leukemia HL-60 cells. Our results indicate that exposure to these
      compounds causes a loss in cell viability by activating the apoptotic process, as
      identified by electron microscopy, DNA gel electrophoresis, and flow cytometry.
      The increased generation of ROS induced by these drugs was a relatively early
      event and preceded the loss of DeltaPsi(m). Overexpression of the antiapoptotic
      protein Bcl-2 or Bcl-X(L) prevents antidepressant-induced apoptosis, as well as
      loss of DeltaPsi(m), but does not affect the generation of ROS.

PMID- 11230810
TI  - Numerical simulation of nonlinear feedback model of saccade generation circuit
      implemented in the LabView graphical programming language.
AB  - The object-oriented graphical programming language LabView was used to implement
      the numerical solution to a computational model of saccade generation in
      primates. The computational model simulates the activity and connectivity of
      anatomical strictures known to be involved in saccadic eye movements. The LabView
      program provides a graphical user interface to the model that makes it easy to
      observe and modify the behavior of each element of the model. Essential elements
      of the source code of the LabView program are presented and explained. A copy of
      the model is available for download from the internet.

PMID- 11230811
TI  - An automated system for the mapping and quantitative analysis of
      immunocytochemistry of an inducible nuclear protein.
AB  - We describe here an automated system that accurately maps tissue sections stained
      by immunocytochemistry for an inducible nuclear protein. The sections are scanned
      with a computer-controlled microscope setup hooked to a CCD camera. Raw images
      captured at high resolution are filtered using highly selective criteria for the
      recognition of labeled cell nuclei. The total population of recognized labeled
      nuclei is then divided into separate bins, according to their labeling
      intensities. Finally, information about both the position and labeling intensity
      of labeled nuclei is represented in average density maps. The system was
      optimized for the quantitative mapping of neuronal cells expressing the inducible
      gene ZENK in the brain of songbirds, in response to stimulation with song, but
      should be of general applicability for the mapping of inducible nuclear proteins.

PMID- 11230812
TI  - Cerebral blood flow determinations using fluorescent microspheres: variations on
      the sedimentation method validated.
AB  - We validate a modification of the sedimentation method for measuring fluorescent
      microspheres (FM) that improves the determination of regional cerebral blood flow
      (rCBF). Our FM method for rCBF determination is compared to the radioactive
      microspheres (RM) method for rCBF measurement by simultaneous injection of one
      radioactive and two fluorescent labeled doses, at two separate time points, into
      the left ventricle of a pig. The pig was killed, the brain and spinal cord
      removed, and divided into 92 pieces averaging 0.83 g. Our modifications to FM
      analysis by sedimentation includes: 2 instead of 1 week of autolysis, pellet
      washing with 1% Triton X-100 instead of 0.25% Tween 80, phosphate buffer addition
      during rinse, fluorescent dye extraction using 2-ethoxyethylacetate instead of 2
      (2-ethoxyethoxy)ethyl acetate and polypropylene instead of glass tubes. Comparing
      rCBF using Sc46 RM, to yellow-green and orange FM, yielded mean differences of
      0.026 and 0.021 ml/min per piece, respectively. Sn(113) RM compared to blue-green
      and scarlet FM gave mean differences of -0.010 and 0.137 ml/min per piece,
      respectively. All RM-FM differences, except those for scarlet FM, are within
      acceptable limits. This assay provides a reliable method for determining rCBF.

PMID- 11230813
TI  - Simultaneous measurement of tyrosine hydroxylase activity and phosphorylation in
      bovine adrenal chromaffin cells.
AB  - A method for simultaneous measurement of tyrosine hydroxylase (TH) activation and
      phosphorylation in permeabilised and intact bovine adrenal chromaffin cells
      (BACCs) was established. Permeabilised cells were stimulated with cyclic AMP (1-
      10 microM) in the presence of [32P]ATP and L-[carboxyl-(14)C]tyrosine. Intact
      BACCs were preincubated with 32P(i) for 3 h and stimulated with forskolin (1--5
      microM) in the presence of L-[carboxyl-(14)C]tyrosine. On stimulation each well
      was covered with a sealed 'chimney' fitted with a small plastic cup containing
      300 microl of 1.0 M NaOH that trapped the 14CO(2) released. TH activity was
      determined by measuring 14C radioactivity. TH phosphorylation was measured in the
      same cells by separating the solubilized proteins on SDS PAGE followed by
      autoradiography and/or HPLC analysis. It was found that H89, a protein kinase A
      inhibitor, significantly blocked both TH phosphorylation and activation in
      response to cyclic AMP in permeabilised cells. However, in intact cells, H89 was
      effective only in respect to forskolin-stimulated TH activity and did not block
      the forskolin-stimulated TH phosphorylation of Ser-40. The reason(s) for this
      lack of correlation between TH activation and phosphorylation is presently not
      understood.

PMID- 11230814
TI  - Efficacy of a low volume recirculating superfusion chamber for long term
      administration of expensive drugs and dyes.
AB  - We have characterized the efficacy of a low volume (2 ml) two-compartment
      experimental chamber in which a gas inflow equilibrates and recirculates the
      bathing fluid. This type of chamber is suitable for experiments employing en bloc
      preparations that require the administration of expensive molecular probes. The
      fluid in the chamber is pumped from a compartment holding the preparation to an
      elevated reservoir compartment using gas bubbles. The fluid returns via gravity
      along a different path. The flow rate of superfusate in the chamber was 30 ml
      min(-1). To determine the effectiveness of the chamber in dissolving gas, we
      filled the chamber with bicarbonate-buffered physiological saline and measured pH
      and P(O(2)) with ion-selective and Clark-style microelectrodes. Steady state
      values of pH and P(O(2)) in the chamber were almost identical to those in an
      external tonometer bubbled vigorously with the same gas mixture. When CO(2) was
      increased from 2 to 4.4%, the chamber pH fell with a time constant of 56 s (about
      twice that of the tonometer). To determine the effectiveness of gas exchange
      between a brain preparation and the fluid in the chamber we measured pH and
      P(O(2)) depth profiles of the in vitro tadpole brainstem. We found virtually no
      unstirred layer owing to excellent mixing and the high flow created by the
      recirculating mechanism. We demonstrate that despite the high flow rates,
      preparations are mechanically stable allowing intracellular electrophysiological
      recordings.

PMID- 11230815
TI  - Paw withdrawal threshold in the von Frey hair test is influenced by the surface
      on which the rat stands.
AB  - The effect of testing surface on the rat hind paw withdrawal threshold in the von
      Frey hair test is investigated in this study. The data indicate that wire mesh,
      which is typically used to apply von Frey hairs, may have an effect on the paw
      withdrawal threshold. For example, in control rats tested on the wire mesh,
      variability in the withdrawal threshold was observed between the left and the
      right hind paws (51.04+/-12.29 and 64.31+/-9.37 g, respectively) and on different
      days of testing (35.24+/-9.54 and 45.83+/-12.97 g for the left and right hind
      paws, respectively, 7 days later). In an attempt to reduce this variability, a
      customized platform was used to measure the von Frey hair-induced paw withdrawal
      in the rat. It consists of an opaque, flat-surfaced plastic platform with holes
      through which von Frey hairs are inserted and applied to the plantar surface of
      the paw. In control rats tested with von Frey hairs using this customized
      platform, variability in the paw withdrawal thresholds between the left and right
      hind paws in single rats over time as well as between different rats was reduced
      (49.86+/-6.97 and 49.29+/-6.56 g for the left and right hind paws, respectively,
      on day 0; 48.29+/-5.82 and 53.00+/-4.59 g for the left and right hind paws,
      respectively, 7 days later). Furthermore, in rats in which a 2 mm polyethylene
      cuff was used to constrict the left common sciatic nerve, the ipsilateral as well
      as the contralateral hind paw withdrawal thresholds were decreased (2.45+/-0.65
      and 26.09+/-5.86 g, respectively, 7 days later). In similar rats tested on the
      wire mesh, the ipsilateral but not the contralateral paw withdrawal threshold
      decreased (12.80+/-2.21 and 65.00+/-10.28 g, respectively, at 7 days). The data
      suggest that the flat surface and opaque properties of the customized platform
      enable accurate, reliable and repeatable measurements of ipsilateral and
      contralateral paw withdrawal threshold using von Frey hairs in normal and nerve
      injured rats.

PMID- 11230816
TI  - Labelling of peptides with 1.4-nm gold particles to demonstrate their binding
      sites in the rat spinal cord.
AB  - Recently we presented a method to label the neuropeptide substance P with a 1.4
      nm gold particle covalently bound at the N-terminus that can be used for
      demonstrating its binding sites in histological sections. In this study we
      examined whether the peptides neuropeptide Y, somatostatin, calcitonin gene
      related peptide and bradykinin can be labelled in the same way. Polyacrylamide
      gel electrophoresis revealed a reduction in mobility for peptide-gold conjugates
      over gold particles alone consistent with peptide binding. In cryostat sections
      of the rat lumbar spinal cord, the peptides showed a distinct binding pattern in
      the grey matter corresponding to data of studies using autoradiographic methods.
      Therefore, we conclude that this simple and fast method can be used for labelling
      peptides in general to demonstrate their binding sites in histological sections,
      provided the peptide binds by its C-terminus.

PMID- 11230817
TI  - Utility of a tripolar stimulating electrode for eliciting dopamine release in the
      rat striatum.
AB  - The present study evaluated tripolar stimulating electrodes for eliciting
      dopamine release in the rat brain in vivo. Stimulating electrodes were placed
      either in the medial forebrain bundle or in the ventral mesencephalon associated
      with the ventral tegmental area and substantia nigra. The concentration of
      extracellular dopamine was monitored in dopamine terminal fields at 100-ms
      intervals using fast-scan cyclic voltammetry at carbon-fiber microelectrodes. To
      characterize the stimulated area, recordings were collected in several striatal
      regions including the caudate putamen and the core and shell of the nucleus
      accumbens. The tripolar electrode was equally effective in stimulating dopamine
      release in medial and lateral regions of the striatum. In contrast, responses
      evoked by a bipolar electrode were typically greater in one mediolateral edge
      versus the other. The added size of the tripolar electrode did not appear to
      cause complications as signals were stable over the course of the experiment (3
      h). Subsets of mesostriatal dopamine neurons could also be selectively activated
      using the tripolar electrode in excellent agreement with previously described
      topography. Taken together, these results suggested that the tripolar stimulating
      electrode is well suited for studying the regulation of midbrain dopamine neurons
      in vivo.

PMID- 11230818
TI  - Third annual conference on new and re-emerging infectious diseases: in honor of
      Norman Dion Levine.

PMID- 11230819
TI  - Microsporidia: emerging pathogenic protists.
AB  - Microsporidia are eukaryotic spore forming obligate intracellular protozoan
      parasites first recognized over 100 years ago. These organisms infect all of the
      major animal groups and are now recognized as opportunistic pathogens of humans.
      Microsporidian spores are common in the environment and microsporidia pathogenic
      to humans have been found in water supplies. The genera Nosema, Vittaforma,
      Brachiola, Pleistophora, Encephalitozoon, Enterocytozoon, Septata (reclassified
      to Encephalitozoon) and Trachipleistophora have been found in human infections.
      These organisms have the smallest known eukaryotic genomes. Microsporidian
      ribosomal RNA sequences have proven useful as diagnostic tools as well as for
      phylogenetic analysis. Recent phylogenetic analysis suggests that Microsporidia
      are related to the fungi. These organisms are defined by the presence of a unique
      invasion organelle consisting of a single polar tube that coils around the
      interior of the spore. All microsporidia exhibit the same response to stimuli,
      that is, the polar tube discharges from the anterior pole of the spore in an
      explosive reaction. If the polar tube is discharged next to a cell, it can pierce
      the cell and transfer its sporoplasm into the cell. A technique was developed for
      the purification of polar tube proteins (PTPs) using differential extraction
      followed by reverse phase HPLC. This method was used to purify the PTPs from
      Glugea americanus, Encephalitozoon cuniculi, Enc. hellem and Enc. intestinalis.
      These PTPs demonstrate conserved characteristics such as solubility,
      hydrophobicity, mass, proline content and immunologic epitopes. The major PTP
      gene from Enc. cuniculi and Enc. hellem has been cloned and expressed in vitro.
      The gene sequences support the importance of ER and in the formation of the polar
      tube as suggested by morphologic studies. Analysis of the cloned proteins also
      indicates that secondary structural characteristics are conserved. These
      characteristics are probably important in the function of this protein during the
      eversion/assembly of the polar tube and in providing elasticity and resiliency
      for sporoplasm passage.

PMID- 11230820
TI  - Anthropogenic environmental change and the emergence of infectious diseases in
      wildlife.
AB  - By using the criteria that define emerging infectious diseases (EIDs) of humans,
      we can identify a similar group of EIDs in wildlife. In the current review we
      highlight an important series of wildlife EIDs: amphibian chytridiomycosis;
      diseases of marine invertebrates and vertebrates and two recently-emerged viral
      zoonoses, Nipah virus disease and West Nile virus disease. These exemplify the
      varied etiology, pathogenesis, zoonotic potential and ecological impact of
      wildlife EIDs. Strikingly similar underlying factors drive disease emergence in
      both human and wildlife populations. These are predominantly ecological and
      almost entirely the product of human environmental change. The implications of
      wildlife EIDs are twofold: emerging wildlife diseases cause direct and indirect
      loss of biodiversity and add to the threat of zoonotic disease emergence. Since
      human environmental changes are largely responsible for their emergence, the
      threats wildlife EIDs pose to biodiversity and human health represent yet another
      consequence of anthropogenic influence on ecosystems. We identify key areas where
      existing expertise in ecology, conservation biology, wildlife biology, veterinary
      medicine and the impact of environmental change would augment programs to
      investigate emerging diseases of humans, and we comment on the need for greater
      medical and microbiological input into the study of wildlife diseases.

PMID- 11230821
TI  - Specific detection of Entamoeba histolytica DNA by hemolysin gene targeted PCR.
AB  - Diagnostic differentiation of pathogenic Entamoeba histolytica from non
      pathogenic Entamoeba dispar is of great clinical importance. We have developed
      and evaluated a new polymerase chain reaction (PCR) assay (haemo-PCR) based on
      the novel E. histolytica hemolysin gene HLY6. The specificity of this assay was
      confirmed by analyzing different Entamoeba species, faeces samples, human and
      bacterial DNA, and digestion of amplification products with appropriate
      restriction enzymes. The sensitivity was confirmed by serial dilutions of E.
      histolytica HM-1:IMSS DNA in the excess of human DNA. Totally, 45 clinical
      samples were analyzed by the haemo-PCR assay including amoebic liver abscess
      (ALA) fluids from 23 patients suspected for amoebiasis, four faeces samples
      containing E. histolytica and E. dispar, and positive and negative controls. The
      results were compared with those obtained with PCRs for cystein-rich surface
      protein (P30) and small subunit ribosomal RNA (ssu rRNA) genes. The haemo-PCR
      gave a positive result in 18 (89%) ALA fluids compared with 14 (77%) and five
      (28%) by PCR for p30, and ssu rRNA, respectively. PCR products were obtained only
      from specimens containing E. histolytica DNA. The haemo-PCR assay was therefore
      found to be a valuable diagnostic tool for identification of E. histolytica
      infections both in faeces and ALA samples.

PMID- 11230822
TI  - Trypanosoma cruzi: presence of the two major phylogenetic lineages and of several
      lesser discrete typing units (DTUs) in Chile and Paraguay.
AB  - Multilocus enzyme electrophoresis (MLEE) of 99 Chilean and 11 Paraguayan stocks
      of Trypanosoma cruzi, the agent of Chagas disease, was performed for 22 variable
      genetic loci. As previously shown for this parasite in other geographic areas, a
      pattern of long-term clonal evolution of T. cruzi genotypes was inferred, both by
      strong departures of Hardy-Weinberg expectations and high linkage disequilibrium.
      The presence of the two major phylogenetic lineages that subdivide the species T.
      cruzi [Tibayrenc, M., 1995. Population genetics of parasitic protozoa and other
      microorganisms. In: Baker, J.R., Muller, R., Rollinson, D. (Eds.), Advances in
      Parasitology, vol. 36, Academic Press, New York, pp. 47-115; Souto, R.P.,
      Fernandes, O., Macedo, A.M., Campbell, D.A., Zingales, B., 1996. DNA markers
      define two major phylogenetic lineages of Trypanosoma cruzi. Mol. Biochem.
      Parasitol. 83, 141-152], and of several lesser genetic subdivisions ('discrete
      typing units' or DTUs; Tibayrenc, M., 1998a. Genetic epidemiology of parasitic
      protozoa and other infectious agents: the need for an integrated approach. Int.
      J. Parasitol. 28 (1), 85-104; Tibayrenc, M., 1998b. Beyond strain typing and
      molecular epidemiology: integrated genetic epidemiology of infectious diseases.
      Parasitol. Today 14, 323-329; Tibayrenc, M., 1998c. Integrated genetic
      epidemiology of infectious diseases: the Chagas model. Mem. Inst. Oswaldo Cruz 93
      (5), 577-580), was recorded in this region. Comparison between clonal populations
      in sylvatic and domestic transmission cycles of the disease in Chile strongly
      suggests that these two cycles are at least partially separated from one another.

PMID- 11230823
TI  - Socio-economic and environmental protective/risk factors for severe malaria in
      Thailand.
AB  - We conducted a cross-sectional study to identify the socio-economic and
      environmental protective/risk factors for severe malaria in Thailand. Forty-six
      cases of severe malaria, 72 cases of non-severe malaria with high parasite
      biomass and 40 mild malaria cases were included. When comparing severe malaria
      and non-severe malaria with high parasite biomass, specific logistic regression
      models showed a significant protective effect for helminths, adjusted odds ratio
      0.24 (0.07-0.78) for low body mass index (BMI), adjusted odds ratio 0.11 (0.02
      0.58). When comparing severe and mild malaria, a longer residence duration,
      adjusted odds ratio 0.36 (0.09-0.83) and the use of antimalarial self-medication,
      adjusted odds ratio 0.08 (0.009-0.84) were associated with protection from severe
      malaria. Using stepwise logistic regression with all the variables inserted in
      the model yielded similar results. These findings suggest specific immunity and
      self-medication control parasite multiplication whereas helminths and
      malnutrition more specifically affect the pathogenesis of severe malaria.

PMID- 11230824
TI  - Differences between coding and non-coding regions in the Trichomonas vaginalis
      genome: an actin gene as a locus model(1).
AB  - The sequence of a cloned genomic fragment of Trichomonas vaginalis containing a
      complete actin gene was determined. An uninterrupted open reading frame of 1128
      nucleotides was found that codes for an actin gene. Two overlapped consensus
      promoter sequences for T. vaginalis were found 12 nucleotides upstream the actin
      initiation codon. In addition to actin, two incomplete open reading frames were
      found at the 5' and 3' ends of the clone. These two sequences are expressed and
      showed similarity to adenylate cyclase genes and a yeast hypothetical protein.
      The overall sequence showed a higher G+C content and a lower frequency of
      repeated sequences in the coding regions when compared with the non-coding
      regions. A similar unequal nucleotide distribution was found in various T.
      vaginalis genes retrieved from data bases.

PMID- 11230825
TI  - Prospective risk of morbidity in relation to multiplicity of infection with
      Plasmodium falciparum in Sao Tome.
AB  - The prospective risk of acute morbidity was analysed in relation to multiplicity
      of Plasmodium falciparum infection in 491 individuals in a peri-urban community
      in Sao Tome. In an initial cross-sectional survey, 40.5% of individuals were
      recorded by microscopy as infected with P. falciparum, and by PCR 60.5%, with the
      maximum prevalence in children aged 5-10 years. PCR-RFLP typing of the msp-2 gene
      of P. falciparum found a mean of 2.4 parasite genotypes per infected person, with
      little age dependence in this multiplicity and a total of 43 different msp-2
      alleles identified. None of these were unique for Sao Tome. Study participants
      were encouraged to report to a project worker whenever they suffered a febrile
      illness. During the 3 months following the parasitological survey the recorded
      incidence rates decreased with increasing baseline msp-2 multiplicity, both for
      P. falciparum-positive episodes and for fever without parasitaemia. While this is
      consistent with suggestions that multiple P. falciparum infections may protect
      against super-infecting parasites, confounding by patterns of health service
      usage is an alternative explanation. The incidence of clinical malaria episodes
      was only a little higher in children than in adults. This weak age-dependence in
      clinical immunity might be a consequence of a cohort effect resulting from
      resurgence of the disease after the breakdown of malaria control programs in the
      1980s.

PMID- 11230826
TI  - The relationship between the parasitological prevalence of trypanosomal
      infections in cattle and herd average packed cell volume.
AB  - The relationship between prevalence of trypanosomal infections (Trypanosoma
      congolense) and average packed cell volume (PCV) in herds of communally managed
      adult Angoni breed cattle was investigated in four districts of eastern Zambia.
      In all areas, regression analyses showed that the herd average PCV decreased with
      increasing prevalence of trypanosomal infections. The slope of the equation
      between average PCV and trypanosome prevalence decreased with increasing
      prevalence of trypanosomal infections. For the same increase in prevalence of
      trypanosomal infection, the decrease in herd PCV was higher in the areas with low
      to medium prevalence. Season of sampling also determined the slope of the
      regression equation. For the same increase in prevalence of trypanosomal
      infection, the decrease in herd PCV was higher during the dry compared to the
      rainy season suggesting that trypanosomosis is less well tolerated during the dry
      season. Results from the study suggest that the relationship between the
      prevalence of trypanosomal infections and herd average PCV could be a useful tool
      in the management of trypanosomosis and planning of its control. Reasons for the
      spatial and temporal variations in the relationship are discussed.

PMID- 11230827
TI  - Non-filarial elephantiasis in the Mt. Elgon area (Kapchorwa District) of Uganda.
AB  - Following reports of a high frequency of elephantiasis in Kwen County (Kapchorwa
      District) on the slopes of Mt. Elgon in Uganda, a baseline survey for lymphatic
      filariasis was carried out in three villages in the affected area. Individuals
      aged 1 year and above were examined for chronic manifestations of lymphatic
      filariasis, and for specific circulating filarial antigens and microfilariae of
      Wuchereria bancrofti. Elephantiasis was observed in all age groups from 10 years
      and above. The overall prevalence was 4.5%, and the prevalence among individuals
      aged >/=20 years was 8.2%. Males and females were equally affected. However,
      there were only few cases of hydrocele (overall prevalence in males of 1.0%) and
      blood examinations were negative for W. bancrofti circulating antigens and
      microfilariae. Sampling of potential filariasis mosquito vectors revealed low
      densities of Anopheles gambiae s.l. and An. funestus, and none of these were
      infected with filarial larvae. In view of the low hydrocele to elephantiasis
      ratio, the absence of filarial infection in humans and mosquitoes, the high
      altitude (1500-2200 m above sea level) and the volcanic soil type, it is
      concluded that elephantiasis seen in this area is not of filarial origin but most
      likely is due to podoconiosis (endemic non-filarial elephantiasis).

PMID- 11230828
TI  - Imported Plasmodium vivax malaria in France: geographical origin and report of an
      atypical case acquired in Central or Western Africa.
AB  - A total of 73 cases of Plasmodium vivax infections acquired in Western or Central
      Africa were diagnosed on microscopical criteria in French travellers from 1995 to
      1998. We report a case of P. vivax infection in a non immune traveller confirmed
      by polymerase chain reaction and presenting an atypical P. ovale morphology. The
      infection was acquired in Western or Central Africa. These microscopical
      observations, together with the molecular evidence for P. vivax in Western and
      Central Africa suggest that P. vivax is transmitted in this area despite lacking
      the Duffy receptor in autochthonous population.

PMID- 11230829
TI  - Usefulness of transthoracic echocardiography as a tool for risk stratification of
      patients undergoing major noncardiac surgery.
AB  - Transthoracic echocardiography (TTE) is frequently ordered before noncardiac
      surgery, although its ability to predict perioperative cardiac complications is
      uncertain. To evaluate the incremental information provided by TTE after
      consideration of clinical data for prediction of cardiac complications after
      noncardiac surgery, 570 patients who underwent TTE before major noncardiac
      surgery at a university hospital were studied. Preoperative clinical data and
      clinical outcomes were collected prospectively according to a structured
      protocol. TTE data included left ventricular (LV) function, hypertrophy indexes,
      and Doppler-derived measurements. In univariate analyses, preoperative systolic
      dysfunction was associated with postoperative myocardial infarction (odds ratio
      [OR] 2.8, 95% confidence interval [CI] 1.1 to 7.0), cardiogenic pulmonary edema
      (OR 3.2, 95% CI 1.4 to 7.0), and major cardiac complications (OR 2.4, 95% Cl 1.3
      to 4.5). Moderate to severe LV hypertrophy, moderate to severe mitral
      regurgitation, and increased aortic valve gradient were also associated with
      major cardiac events (OR 2.3, 95% CI 1.2 to 4.6; OR 2.2, 95% CI 1.1 to 4.3; OR
      2.1, 95% CI 1.0 to 4.5, respectively). In logistic regression analysis, models
      with echocardiographic variables predicted major cardiac complications
      significantly better than those that included only clinical variables (c
      statistic 0.73 vs 0.68; p <0.05). Echocardiographic data added significant
      information for patients at increased risk for cardiac complications by clinical
      criteria, but not in otherwise low-risk patients. In conclusion, preoperative TTE
      before noncardiac surgery can provide independent information about the risk of
      postoperative cardiac complications in selected patients.

PMID- 11230830
TI  - Myocardial damage and left ventricular dysfunction in patients with and without
      persistent negative T waves after Q-wave anterior myocardial infarction.
AB  - Persistent T-wave inversions during the chronic stage of Q-wave myocardial
      infarction (MI) indicate the presence of a transmural infarction with a fibrotic
      layer pathologically. The aim of the present study was to examine the relation
      between left ventricular (LV) damage and changes in polarity of the T waves from
      the acute to chronic phase in patients with Q-wave anterior wall MI. We studied
      140 patients with persistent T-wave inversions in leads with Q waves (negative T
      wave group) and 158 patients with positive T waves (positive T-wave group) at 12
      months after anterior MI. In the positive T-wave group, the precordial T waves
      reverted from a negative to a positive morphology < 3 months after MI in 21
      patients (3 M-positive T-wave subgroup), 3 to 6 months in 52 patients (6 M
      positive T-wave subgroup), and 6 to 12 months in 75 patients (12 M-positive T
      wave subgroup). Ten patients had persistent positive T waves without initial T
      wave inversion (persistent positive T-wave group). Wall motion index and LV
      dimension were higher and the wall thickness for the infarct area and LV ejection
      fraction were lower in the negative T-wave than in the positive T-wave groups,
      except the persistent positive T-wave group in the chronic stage (p < 0.0001).
      Wall motion in the infarcted area improved over the course of 1 year in the 3 M-,
      6 M-, and 12 M-positive T-wave subgroups (p < 0.0001), but not in the persistent
      positive T-wave group. Among the patients with T-wave inversions after admission,
      those who had persistent negative T waves after 12 months had worse LV function.
      In patients with initial T-wave inversion, earlier normalization of the
      precordial T waves was associated with greater improvement in LV function.
      Patients with persistent positive T waves without initial negative T waves had
      poorer recovery of LV function than patients with persistent negative T waves. We
      conclude that the presence of inverted T waves in leads with abnormal Q waves 12
      months after MI and the time required for T-wave normalization can be used to
      assess the degree of LV dysfunction.

PMID- 11230831
TI  - Immediate effect of percutaneous myocardial laser revascularization on
      hemodynamics and left ventricular systolic function in severe angina pectoris.
AB  - Experimental data suggest that myocardial revascularization with a high-energy
      laser may cause a significant reduction in left ventricular (LV) function
      immediately after creation of myocardial channels. We sought to determine if
      percutaneous myocardial laser revascularization (PMR) causes immediate
      deterioration in hemodynamic parameters or regional LV systolic function. PMR was
      performed in 40 patients (mean age 62.9 +/- 10.8 years) using the Eclipse Holmium
      laser (26 had PMR alone; 14 patients underwent PMR plus percutaneous coronary
      intervention). Intracardiac pressures and left ventriculograms were recorded
      before and after PMR. Regional wall motion was assessed using the centerline
      method. A mean of 18 +/- 5 channels were created per patient. There was no
      significant change in LV ejection fraction immediately after PMR (56 +/- 9% vs 55
      +/- 10%, p = 0.25). No deterioration in regional wall motion was demonstrated in
      the lased region (mean chord motion for anterior wall PMR: -1.5 +/- 0.8 before vs
      -1.5 +/- 0.8 after the procedure, p = 0.93; inferior wall PMR: -1.5 +/- 0.9
      before vs - 1.6 +/- 0.8 after the procedure, p = 0.43). Similarly, there was no
      change in the number of hypokinetic chords in the treated region. Systemic blood
      pressure, LV end-diastolic pressure, heart rate, and right-sided heart pressures
      were not significantly different after laser revascularization. In patients with
      refractory angina, PMR did not cause immediate deterioration in hemodynamic
      status or regional LV function.

PMID- 11230832
TI  - Safety, feasibility, and diagnostic accuracy of accelerated high-dose
      dipyridamole stress echocardiography.
AB  - Protocols for dipyridamole stress testing have evolved in the last 16 years in
      the neverending quest of optimal diagnostic accuracy and user friendliness.
      Higher dipyridamole dose in a shorter infusion time provides higher sensitivity,
      but concern over safety is still controversial. An accelerated high-dose (0.84
      mg/kg in 6 minutes without atropine) dipyridamole stress test was performed on
      1,295 patients in 2 echocardiographic laborotories: Institute of Clinical
      Physiology of Pisa and Niguarda Hospital of Milan. During testing, there were no
      deaths and no patients had ventricular fibrillation. Major adverse reactions
      occurred in 3 cases (1 every 431 studies): 1 myocardial infarction, 1 brief
      cardiac asystole, and 1 transient ischemic attack. Overall feasibility was 97%.
      In 66 patients with normal function at rest who were evaluated off therapy, with
      coronary angiography performed independently of test results, the accelerated
      high-dose protocol showed a sensitivity of 85% (confidence interval [CI] 73% to
      92%) and a specificity of 93% (CI 83% to 97%) for angiographically assessed
      coronary artery disease (quantitatively assessed diameter reduction > or = 50%).
      Diagnostic accuracy of the accelerated high dose was 89% (CI 79% to 95%). Thus,
      accelerated high-dose dipyridamole stress echocardiography was reasonably safe
      and well tolerated. This protocol is especially appealing for its excellent
      diagnostic accuracy coupled with the short imaging time and no need for drug
      cocktails.

PMID- 11230833
TI  - Application of tissue Doppler to interpretation of dobutamine echocardiography
      and comparison with quantitative coronary angiography.
AB  - The main limitation of dobutamine echocardiography (DE) is its subjective
      interpretation. We sought to reduce the need for expert interpretation by
      developing a quantitative approach to DE using myocardial Doppler velocity (MDV)
      in 242 patients undergoing DE. In 128 patients with a normal dobutamine
      echocardiogram, the normal range was designed to give a specificity of 80%. The
      accuracy of this range was investigated in 114 consecutive patients who underwent
      coronary angiography within 2 months of DE. A standard dobutamine
      echocardiographic protocol was used, with MDV gathered from color tissue Doppler
      at rest and peak stress. Wall motion at these stages was scored by experienced
      observers using a 16-segment model and MDV was measured off-line. Sensitivity and
      specificity of wall motion scoring and MDV were obtained by comparison with
      angiographic evidence of disease, defined as stenosis > 50% of the coronary
      artery diameter. The normal range in tethered segments (septum, anteroseptum, and
      inferior) was > or = 7 cm/s in the basal segments and > or = 5 cm/s in the
      midsegments. In the free wall (anterior, lateral, and posterior), the cutoff was
      > or = 6 cm/s in the base and > or = 4 cm/s in the midventricle. Of 114 patients
      undergoing angiography, 84 (75%) had significant stenoses, and the sensitivity of
      wall motion scoring and MDV were 88% and 83%, respectively, with specificities of
      81% and 72% (p = NS). The accuracy was similar overall (86% vs 80%), as well as
      in each vascular territory. These data suggest that a fully quantitative
      interpretation of DE using site-specific normal ranges of tissue Doppler, which
      account for regional variations of base-apex function, is feasible and equivalent
      in accuracy to expert wall motion scoring.

PMID- 11230834
TI  - Prognostic importance of concomitant heparin with eptifibatide in acute coronary
      syndromes. PURSUIT Investigators. Platelet Glycoprotein IIb/IIIa in Unstable
      Angina: Receptor Suppression Using Integrilin Therapy.
AB  - Platelet glycoprotein IIb/IIIa inhibitors have been extensively studied in the
      treatment of patients with ischemic heart disease. Data regarding the use of
      these agents in the absence of concomitant intravenous heparin have been
      conflicting. We sought to determine, using propensity analysis, whether the
      benefit of eptifibatide, a IIb/IIIa inhibitor, in the treatment of acute coronary
      syndromes is affected by the concurrent administration of heparin. By trial
      design, patients were randomized to either eptifibatide or placebo, whereas use
      of intravenous heparin was left to the discretion of treating physicians. The
      effect of eptifibatide on the 30-day composite end point of death or myocardial
      infarction was studied in patients who received heparin and those who did not.
      Propensity analysis methods were used to control for confounding and presumed
      selection biases. Among 5,576 patients who were receiving heparin when the bolus
      dose of the study drug was administered, eptifibatide was associated with a
      reduced composite end point rate (13%) compared with that of placebo (14.5% vs
      16.6%, p = 0.03). In contrast, among 1,441 patients who were not receiving
      heparin, there was no difference in 30-day event rates with eptifibatide compared
      with placebo (13.7% vs 13.1%, p > 0.7). After a propensity score for use of
      heparin was developed, however, use of heparin did not affect the reduced risk
      associated with eptifibatide (adjusted relative risk [RR] for heparin
      eptifibatide interaction term 0.90, 95% confidence interval [CI] 0.61 to 1.32, p
      > 0.5), but the propensity for heparin use was a strong predictor of events
      (adjusted RR 1.76, 95% CI 1.42 to 2.17, p < 0.001). The use of eptifibatide
      independently predicted a lower risk of events (adjusted RR 0.31, 95% CI 0.10 to
      0.93, p = 0.04). Thus, the apparent positive impact of heparin on the benefits of
      eptifibatide therapy was largely due to confounding and bias.

PMID- 11230835
TI  - Meta-analysis of effectiveness and safety of abciximab versus eptifibatide or
      tirofiban in percutaneous coronary intervention.
AB  - Three platelet glycoprotein (GP) IIb/IIIa receptor antagonists have been
      evaluated in patients undergoing percutaneous coronary intervention (PCI). One of
      these agents, abciximab, is structurally and pharmacologically quite different
      from the other 2, eptifibatide and tirofiban. We conducted a meta-analysis to
      determine whether different antagonist types achieved different clinical
      outcomes, possibly related to their structural differences. Odds ratios (OR) were
      calculated and a random effects model was used to combine the outcomes of 14,644
      patients enrolled in 8 prospective, randomized, placebo-controlled clinical
      trials assessing treatment with a GP IIb/IIIa inhibitor to prevent ischemic
      complications of PCI. Neither abciximab (OR 0.69; 95% confidence interval [CI]
      0.4 to 1.9) nor eptifibatide or tirofiban treatment (OR 0.74; 95% CI 0.4 to 1.28)
      resulted in reductions in mortality. Only the abciximab-treated patients had
      reductions in myocardial infarction (4.3% vs 8.5%, OR 0.49; 95% CI 0.40 to 0.59).
      There was no effect of eptifibatide or tirofiban on myocardial infarction (OR
      0.85; 95% CI 0.69 to 1.04). Urgent revascularization was reduced in both
      abciximab-treated (2.7% vs 6.2%, OR 0.42; 95% CI 0.34 to 0.53) and eptifibatide-
      and tirofiban-treated (4.2% vs 5.5%, OR 0.76; 95% CI 0.60 to 0.96) groups. Only
      abciximab-treated patients had increased major bleeding (5.8% vs 3.8%; OR 1.53;
      95% CI 1.24 to 1.90). There was no effect of eptifibatide or tirofiban on major
      bleeding (5.0% vs 4.3%; OR 1.19; 95% CI 0.94 to 1.52). Thus, significant
      differences exist between clinical outcomes achieved by abciximab and those
      achieved by eptifibatide or tirofiban following PCl procedures.

PMID- 11230836
TI  - Effects of quinapril on clinical outcome after coronary artery bypass grafting
      (The QUO VADIS Study). QUinapril on Vascular Ace and Determinants of Ischemia.
AB  - The QUO VADIS study was designed to explore whether 1 year of angiotensin
      converting enzyme inhibition with quinapril (40 mg/day) would decrease ischemia
      in patients who underwent coronary artery bypass grafting (CABG). Patients (n =
      149) scheduled for CABG were randomized 4 weeks before surgery. Study medication
      was used from randomization up to 1 year after CABG. Exercise testing was
      performed at randomization; the exercise test was repeated 1 year after CABG and
      patients underwent 48-hour Holter monitoring. Clinical ischemic events were
      recorded and defined as death, revascularization, myocardial infarction,
      recurrence of angina pectoris, ischemic stroke, or transient ischemic attack.
      Baseline characteristics were similar between groups. Total exercise time
      increased overall by 75 +/- 76 seconds 1 year after CABG (placebo +79 +/- 75
      seconds, quinapril +72 +/- 79 seconds, p = 0.6). All patients had ischemic ST
      segment changes at randomization; 33% of patients had ischemic ST-segment changes
      1 year after CABG (placebo 29%, quinapril 37%, p = 0.4). On Holter monitoring,
      the number of patients experiencing > or = 1 episodes of ischemia was equal in
      both groups. Treatment with quinapril significantly reduced clinical ischemic
      events after CABG: 15% in patients on placebo versus 4% of patients on quinapril
      (hazard ratio 0.23, 95% confidence interval 0.06 to 0.87, p = 0.02). Long-term
      quinapril treatment significantly reduced clinical ischemic events within 1 year
      after CABG, although ischemia at exercise testing and Holter monitoring was
      unchanged.

PMID- 11230837
TI  - Evaluation of coronary risk factors in patients with heterozygous familial
      hypercholesterolemia.
AB  - Age at onset of clinically manifested coronary artery disease (CAD) varies widely
      among patients with familial hypercholesterolemia (FH). A number of factors in
      addition to high low-density lipoprotein cholesterol (LDL) have been suggested as
      predictors of risk among patients with FH, but a comprehensive examination of
      their utility is lacking. We therefore measured plasma lipids, carotid intima
      medial thickness, and a variety of coronary risk factors in 262 patients with FH
      > or = 30 years old (68 of whom had premature CAD). Age (p < 0.0001) and gender
      were the most important determinants of premature CAD risk, with men having 5.64
      times the risk of women (p < 0.0001). In addition, cigarette smoking (odds ratio
      [OR] 2.71, p = 0.026), smaller LDL as determined by the LDL cholesterol/LDL
      apolipoprotein B ratio (OR 2.60, p = 0.014), and white blood cell count (p =
      0.014) were also statistically significant risk factors. Lipoprotein(a) and the
      presence of xanthoma were associated with risk only in very early coronary cases.
      After correction for age, carotid intima-media thickness was not associated with
      CAD risk. Insulin, fibrinogen, homocysteine, plasma C-reactive protein, and the
      angiotensin-converting enzyme insertion/deletion polymorphism were unrelated to
      risk in this cohort. These results provide little justification for extensive
      investigation of risk factors among patients with FH, at least for the risk
      factors examined here. Rather, the inherent high LDL cholesterol of these
      patients should be the focus of preventive efforts. The novel finding of
      increased risk with smaller LDL may prove useful but needs further confirmation.

PMID- 11230838
TI  - Comparison of efficacy and safety of atorvastatin (10mg) with simvastatin (10mg)
      at six weeks. ASSET Investigators.
AB  - The 6-week efficacy and safety of atorvastatin versus simvastatin was determined
      during a 54-week, open-label, multicenter, parallel-arm, treat-to-target study.
      In all, 1,424 patients with mixed dyslipidemia (triglyceride 200 to 600 mg/dl
      [2.26 to 6.77 mmol/L]) were stratified to 1 of 2 groups (diabetes or no
      diabetes). Patients were then randomized to receive either atorvastatin 10 mg/
      day (n = 730) or simvastatin 10 mg/day (n = 694). Efficacy was determined by
      measuring changes from baseline in lipid parameters including low-density
      lipoprotein (LDL) cholesterol, total cholesterol, triglycerides, and
      apolipoprotein B. Compared with simvastatin, atorvastatin produced significantly
      greater (p < 0.0001) reductions from baseline in LDL cholesterol (37.2% vs
      29.6%), total cholesterol (27.6% vs 21.5%), triglycerides (22.1% vs 16.0%), the
      ratio of LDL cholesterol to high-density lipoprotein (HDL) cholesterol (41.1% vs
      33.7%), and apolipoprotein B (28.3% vs 21.2%), and a comparable increase from
      baseline in HDL cholesterol (7.4% vs 6.9%). Atorvastatin was also significantly
      (p < 0.0001) more effective than simvastatin at treating the overall patient
      population to LDL cholesterol goals (55.6% vs 38.4%). Fewer than 6% of patients
      in either treatment group experienced drug-attributable adverse events, which
      were mostly mild to moderate in nature. Diabetic patients treated with either
      statin had safety characteristics similar to nondiabetics, with atorvastatin
      exhibiting superior efficacy to simvastatin. In conclusion, atorvastatin, at a
      dose of 10 mg/day, is more effective than simvastatin 10 mg/day at lowering
      lipids and reaching LDL cholesterol goals in patients with mixed dyslipidemia.
      Both statins are well tolerated with safety profiles similar to other members of
      the statin class.

PMID- 11230839
TI  - Usefulness of electron beam tomography to detect progression of coronary and
      aortic calcium in middle-aged women.
AB  - Electron beam tomography (EBT) permits the noninvasive quantification of coronary
      and aortic calcium as a marker of atherosclerosis. Coronary and aortic calcium
      are strongly related to premenopausal cardiovascular risk factors in middle-aged
      women. This report evaluates changes in coronary and aortic calcium over an
      average of 18 months in 80 women. Measurement variation over time and between
      readings is also evaluated in these women who were followed through the
      menopausal transition. Eight years after menopause, 80 women (average age 63
      years) underwent serial EBT of the coronary arteries and aorta separated by 18
      months. Calcium scores were based on the number and density of calcific deposits.
      Duplicate readings were obtained to evaluate the effect of reading variation on
      calcium scores. At baseline, the median calcium score was 0 in the coronary
      arteries and 58 in the aorta. Average change in coronary (+11) and aortic (+112)
      calcium were significantly different from zero (p < 0.001). Reading variability
      did not contribute significantly to the variation in calcium scores. Extent of
      calcium in the coronary arteries was associated with progression of calcium in
      the aorta (p = 0.013). Both coronary and aortic calcium were significantly
      associated with premenopausal cardiovascular risk factors. Thus, progression of
      coronary and aortic calcium using EBT can be observed over a short time in
      healthy middle- aged women.

PMID- 11230840
TI  - Effects of omapatrilat on systemic arterial function in patients with chronic
      heart failure.
AB  - The mechanisms of action of omapatrilat, an agent that inhibits both neutral
      endopeptidase 24.11 and angiotensin-converting enzyme, on arterial function in
      patients with heart failure have not been previously reported. Forty-eight
      patients in New York Heart Association functional class II to III, left
      ventricular ejection fraction < or = 40%, and in sinus rhythm were randomized to
      a dose-ranging (2.5, 5, 10, 20, or 40 mg) study of omapatrilat for 12 weeks.
      Measurements were obtained at baseline and 12 weeks. Decreases in systolic (25.0
      +/- 4.5 vs 2.8 +/- 5.0 mm Hg, p < 0.05) and mean arterial (13.9 +/- 3.0 vs 0.3 +/
      3.3 mm Hg, p < 0.05) pressure were seen after 12 weeks of therapy with higher
      doses. Ventricular-arterial coupling was improved with a dose-related decrease in
      augmentation index (-13.8 +/- 1.7% vs +6.1 +/- 2.1%, p < 0.01). There was no
      change in resting forearm blood flow between groups; however, maximum forearm
      vasodilator response during reactive hyperemia increased in the high-dose groups
      compared with the control group (+266 +/- 43% vs - 14 +/- 92%, p < 0.05).
      Omapatrilat induced an increase in postdose plasma atrial natriuretic peptide
      levels (30 +/- 11 vs -2 +/- 7 pmol/L, p < 0.01) in high-dose groups consistent
      with endopeptidase 24.11 inhibition. Omapatrilat shows beneficial changes in
      ventricular-vascular coupling and arterial function in heart failure.

PMID- 11230841
TI  - Effect of losartan on degree of mitral regurgitation quantified by
      echocardiography.
AB  - The objective of this study was to determine the effect of oral losartan on the
      degree of mitral regurgitation (MR). The regurgitant volume and effective
      regurgitant orifice were quantified using 3 methods (flow convergence,
      quantitative Doppler, and quantitative 2-dimensional echocardiography) in 32
      patients (26 men, mean age 67 +/- 14 years) with MR, both at baseline and 4 hours
      after losartan (50 mg orally). Twenty-eight patients were also reevaluated after
      1 month of continued treatment with losartan (50 mg/day). With treatment,
      systolic blood pressure decreased from 143 +/- 16 to 130 +/- 18 mm Hg and left
      ventricular end-systolic wall stress from 173 +/- 46 to 156 +/- 44 g/cm2 (both p
      < 0.001). With treatment, regurgitant volume decreased (from 77 +/- 28 to 64 +/-
      26 ml, - 18 +/- 10%; p < 0.001) in direct relation to the effective regurgitant
      orifice change (from 43 +/- 16 to 37 +/- 15 mm2, -17 +/- 10%; p < 0.001) but
      without significant change in regurgitant gradient or duration. Wide individual
      variability in response was observed unrelated to the magnitude of blood pressure
      changes. Larger reduction in regurgitant volume was observed in patients with a
      marked decrease in wall stress (r = 0.47, p = 0.01) and higher baseline end
      diastolic volume index (r = -0.38, p = 0.03) and regurgitant volume (r = -0.45, p
      = 0.01). Acute improvements were sustained and unchanged at 1 month (all p >
      0.15). Treatment of MR using the angiotensin receptor antagonist losartan
      produces a significant and sustained decrease in the degree of MR, with decreases
      in regurgitant volume and effective regurgitant orifice. However, the changes are
      of modest and variable magnitude.

PMID- 11230842
TI  - Valvular hemodynamics and arrhythmias with exercise following the Ross procedure.
AB  - Pulmonary autograft aortic valve replacement (Ross procedure) is increasing in
      popularity, particularly in children and young adults. We performed a controlled
      study of pediatric and adult Ross procedure patients to evaluate postoperative
      exercise valvular hemodynamics and cardiac rhythm. Thirty-one patients and 24
      controls underwent stress echocardiography. Doppler and 2-dimensional
      echocardiography assessed valvular hemodynamics and right and left ventricular
      size at baseline and after exercise. Electrocardiography monitored cardiac
      rhythm. Patients and controls had neoaortic and neopulmonic valve insufficiency
      ranging from none to moderate that improved or did not change with exercise.
      Baseline and exercise mean peak transaortic gradients were not significantly
      different between patients (baseline 6.3 +/- 3.8 mm Hg, exercise 12.8 +/- 7.3 mm
      Hg) and controls (baseline 6.7 +/- 2.5 mm Hg, exercise 14.3 +/- 5.2 mm Hg).
      However, baseline and exercise mean peak transpulmonic gradients were
      significantly different between patients (baseline 20.7 +/- 9.6 mm Hg, exercise
      45.2 +/- 23.5 mm Hg) and controls (baseline 3.7 +/- 1.3 mm Hg, exercise 10.6 +/-
      3.7 mm Hg). Significant exercise-induced arrhythmias occurred in 8 patients (26%)
      and no controls. Occurrence of arrhythmias correlated with an older age at
      surgery and age at study. After the Ross procedure, patients have valve
      competence and transaortic gradients similar to controls at baseline and with
      exercise. However, patients have significantly increased baseline and exercise
      transpulmonic gradients compared with controls. Furthermore, exercise-induced
      arrhythmias occurred frequently in our patient group and were associated with an
      older age at surgery and age at study.

PMID- 11230843
TI  - Sustained atrial arrhythmias in adults late after repair of tetralogy of fallot.
AB  - We determined the prevalence of sustained atrial tachyarrhythmia (AT) in adults
      late after repair of tetralogy of Fallot (ToF) and examined its impact on
      subsequent heart failure, reoperation, and mortality. Ventricular arrhythmias are
      associated with increased morbidity and mortality in patients with repair of ToF.
      The clinical impact of AT in this population has not been established. A
      retrospective cohort study of 242 patients with repaired ToF identified 29
      patients (prevalence of 12%) with sustained episodes of AT. Patients with
      repaired ToF but without sustained arrhythmia (n = 213) constituted a comparison
      group. Baseline characteristics and clinical outcomes in the 2 groups were
      compared. An echocardiographic analysis compared 15 patients with AT and 15
      matched for age at operation and timing of echocardiography. The development of
      AT was associated with substantial morbidity including congestive heart failure,
      reoperation, subsequent ventricular tachycardia, stroke, and death (combined
      events, 20 of 29 patients [69%]). The rate of combined events (congestive heart
      failure, stroke, and deaths) in the 213 "arrhythmia-free" patients was 30% (64 of
      213 patients). Event-free survival after repair was 18 +/- 2 years for the AT
      group and 28 +/- 1 years for the arrhythmia-free group (p < 0.001). Patients with
      AT were older at surgical repair (25 +/- 16 vs 10 +/- 9 years, p = 0.001), and at
      most recent assessment were aged 48 +/- 12 vs 32 +/- 10 years (p = 0.001). The AT
      group had a higher mean right atrial volume and proportion of significant
      pulmonary regurgitation than matched controls. The development of AT in the adult
      late after ToF repair identifies patients at risk and is associated with older
      age at repair, a higher frequency of hemodynamic abnormalities, and increased
      morbidity.

PMID- 11230844
TI  - Validation of pulmonary venous obstruction by electron beam computed tomography
      in children with congenital heart disease.
AB  - The purpose of this study was to explore the useful imaging findings of electron
      beam computed tomography (EBCT) for diagnosing pulmonary venous obstruction (PVO)
      in children with congenital heart disease. From July 1995 to March 1998, 17
      children (9 girls and 8 boys, aged 7 days to 14 years and 9 months [median 3
      months]) with the diagnosis of PVO were enrolled in this study. All images were
      obtained by EBCT at the end-diastolic phase of the cardiac cycle after
      administration of intravenous iodinated contrast medium. The findings of 25 EBCT
      studies were retrospectively analyzed by 2 radiologists and were correlated with
      echocardiography, angiocardiography, and surgical findings. Main findings on EBCT
      for PVO were (1) structural narrowing, (2) thickened interlobular septa, (3)
      peribronchovascular cuffing, and (4) ground-glass opacity of the alveoli.
      Structural narrowing along the course of the pulmonary venous drainage was the
      most important finding in all examinations (25 of 25). Lung parenchymal changes
      secondary to PVO included thickened interlobular septa (17 of 25),
      peribronchovascular cuffing (15 of 25), and ground-glass opacity of the alveoli
      (8 of 25). Thus, the combination of these findings provides very useful data for
      the definitive diagnosis of PVO. Characteristic electron beam computed
      tomographic findings can validate suspected PVO noninvasively.

PMID- 11230845
TI  - Evaluation of fetal heart dimensions from 12 weeks to term.
AB  - To evaluate whether fetal cardiac measurements can be made in the second
      trimester, we examined a cohort of normal pregnancies between 12 and 18 weeks'
      gestation using state-of-the-art ultrasound equipment. We examined this
      population longitudinally at intervals of 2 weeks, as well as at 32 weeks'
      gestation. From the 4-chamber view we measured the ventricular and atrial cavity
      dimensions, the thickness of the ventricular walls and septum at end-diastole,
      and the annulus dimensions of the mitral and tricuspid valves. Using a variety of
      views we also measured the long and cross-sectional diameters of the atria, the
      aorta, the pulmonary artery and its main left and right branches, the ductus
      arteriosus, and the superior and inferior vena cavae. To test the frequency with
      which measurements could be made, we divided them into measurements that were
      clear and easy to define (statistically good), to those that were unclear
      (statistically bad), or those that were not measured at all (none). Data were
      then analyzed by regression analysis, analysis of variance, and covariance. The
      frequency of reliable measurements varied inversely with gestational age. The
      inflection point for measurements was approximately at 16 weeks. Data from this
      longitudinal study were evaluated against those obtained from our previous study.
      Because no statistical differences were found in measurements between these
      studies where they overlapped, the data were pooled into 1 large group and the
      mean and SEEs calculated for all variables. Our study demonstrates that with
      current transabdominal imaging, fetal cardiac measurements can be made reliably
      in normal fetuses from 16 weeks' gestation onward. The frequency of obtaining
      data in younger normal fetuses suggests it is unlikely that reliable observations
      can be made routinely in abnormal fetuses < 16 weeks old, although this might be
      possible in individual fetuses.

PMID- 11230846
TI  - Biventricular response to supine physical exercise in young adults assessed with
      ultrafast magnetic resonance imaging.
AB  - Simultaneous assessment of left ventricular (LV) and right ventricular (RV)
      response to exercise is limited with the current imaging modalities. Magnetic
      resonance imaging (MRI) techniques are now under development that allow near real
      time evaluation of biventricular function under physical stress. This approach
      may open new avenues to study heart function in response to exercise in health
      and disease. The aim of this study was to evaluate biventricular response to
      supine physical exercise using ultrafast MRI. Biventricular volumes and function
      were examined in 16 healthy volunteers (mean age 18 +/- 2 years) using an
      ultrafast MRI sequence at rest and during an exercise protocol on a MRI
      compatible bicycle ergometer. Exercise level was individualized at the workload
      corresponding to 60% of the maximal oxygen uptake. All subjects completed the
      exercise MRI examination, allowing functional evaluation. Stroke volume of both
      ventricles increased from rest to exercise (left ventricle, 89 +/- 14 ml vs 102
      +/- 19 ml, p < 0.05; right ventricle, 88 +/- 14 ml vs 101 +/- 16 ml, p < 0.05).
      Ejection fraction also increased in both ventricles from rest to exercise (left
      ventricle, 63 +/- 6% vs 74 +/- 6%, p < 0.05; right ventricle, 61 +/- 6% vs 70 +/-
      6%, p < 0.05). End-systolic volume of the left and right ventricles decreased
      from rest to exercise (left ventricle, -33 +/- 12%, p < 0.05; right ventricle, 
      25 +/- 12%, p < 0.05), whereas LV and RV end-diastolic volumes remained
      unchanged. The results fit well with current concepts of cardiac physiology, and
      therefore we conclude that ergometer-induced exercise MRI is a valid approach to
      assess physiologic changes in LV and RV function simultaneously.

PMID- 11230847
TI  - Are angiotensin II receptor blockers more efficacious than placebo in heart
      failure? Implications of ELITE-2. Evaluation of Losartan In The Elderly.
AB  - In the light of the recent randomized controlled trials in chronic heart failure,
      it is now commonly assumed that treatment with an angiotensin-receptor blocker
      (ARB) is equivalent to treatment with an angiotensin-converting enzyme (ACE)
      inhibitor. We performed an imputed placebo analysis using previous placebo-ACE
      inhibitor trials and the current ACE inhibitor-ARB comparison studies, which
      shows that ARBs may not even be superior to placebos, let alone an ACE inhibitor.

PMID- 11230848
TI  - Lipoprotein(a), Friedewald formula, and NCEP guidelines. National Cholesterol
      Education Program.
AB  - The Friedewald low-density lipoprotein cholesterol formula, which is commonly
      used in clinical chemistry laboratories, comprises both low-density lipoprotein
      and lipoprotein(a) cholesterol. This confounder must be recognized and
      appropriately corrected when dealing with subjects with high plasma
      lipoprotein(a) levels.

PMID- 11230849
TI  - Melvin Mayer Scheinman, MD: a conversation with the editor.

PMID- 11230850
TI  - Death or nonfatal stroke in patients with acute myocardial infarction treated
      with tissue plasminogen activator. Participants in the National Registry of
      Myocardial Infarction 2.
AB  - In a retrospective cohort of patients treated in community hospitals, tissue
      plasminogen activator (t-PA) was associated with decreased odds of in-hospital
      death or nonfatal stroke. However, the relative benefit was less evident in older
      patients and women, and some older subgroups did not benefit from treatment.

PMID- 11230851
TI  - Evaluation of long-term survival after successful percutaneous coronary
      intervention among patients with chronic renal failure.
AB  - We studied the long-term outcomes after percutaneous coronary intervention in
      dialysis patients and in patients with chronic renal failure (CRF) (serum
      creatinine > or = 3.0 mg/dl). All-cause mortality at 1 year was 2.9% for the
      control group, 16.2% for the group with CRF, and 14.1% for dialysis patients.
      Cardiac mortality at 1 year was 1.9% for ther control group, 15.2% for the group
      with CRF, and 10.0% for dialysis patients.

PMID- 11230852
TI  - Impact of early percutaneous coronary intervention on short- and long-term
      outcomes in patients with cardiogenic shock after acute myocardial infarction.
AB  - This study assesses the impact of early percutaneous coronary intervention in
      patients presenting with cardiogenic shock after acute myocardial infarction.
      Predictors of in-hospital death include the need for intubation, cardiopulmonary
      resuscitation, and angiographic failure; long-term outcomes at 2 years in
      hospital survivors are favorable.

PMID- 11230854
TI  - Characterization of contraction and perfusion in the lateral border zone between
      normal and ischemic myocardium following coronary occlusion by myocardial
      contrast echocardiography.
AB  - We performed myocardial contrast echocardography with power Doppler imaging
      during left anterior descending occlusion in 10 dogs, and found that video
      intensity and dyssynergy in lateral border zones of ischemic myocardium were
      present, but the video intensity was significantly lower than adjacent
      nonischemic zones. The results of this study demonstrate that levels of perfusion
      and contraction, which are intermediate between normal and central ischemic
      zones, are observed in the border zone with coronary occlusion by myocardial
      contrast echocardography, and may have implications in identifying myocardium
      that will be spared necrosis and in measuring ultimate infarct size.

PMID- 11230853
TI  - Association of white blood cell count with increased mortality in acute
      myocardial infarction and unstable angina pectoris. OPUS-TIMI 16 Investigators.
AB  - We observed in a study of 7,651 patients with acute coronary syndromes that a
      white blood cell (WBC) count of > 10,000 was associated with increased 30-day and
      10-month mortality (6.2% vs 3.2% to 3.6% for WBC count < 10,000; p < 0.000). With
      its simplicity and widespread availability, WBC count could serve as a simple,
      inexpensive, new tool for risk stratification in acute coronary syndromes.

PMID- 11230855
TI  - Effect of simvastatin in preventing progression of carotid artery stenosis.
AB  - This study examines the effect of simvastatin on progression of carotid artery
      stenosis and shows that the drug substantially reversed the anticipated disease
      development. This finding indicates that treatment with simvastatin may reduce
      the risk for stroke in patients with known carotid artery disease.

PMID- 11230856
TI  - Lipid management among coronary artery disease patients with diabetes mellitus or
      advanced age.
AB  - Aggressive lipid management is likely beneficial for coronary artery disease
      patients with diabetes mellitus or of advanced age. Nevertheless, a study of a
      large national sample of patients seen in ambulatory medical practices suggests
      pharmacologic undertreatment in these high-risk groups.

PMID- 11230857
TI  - Complete atrioventricular block after valvular heart surgery and the timing of
      pacemaker implantation.
AB  - The natural history of patients who developed complete atrioventricular block
      after valvular heart surgery was investigated to determine the optimal timing for
      pacemaker implantation. Patients who developed complete atrioventricular block
      within 24 hours after operation, which then persisted for > 48 hours, were
      unlikely to recover; such patients could potentially undergo earlier pacemaker
      implantation if otherwise ready for discharge.

PMID- 11230858
TI  - Aortocardiac fistulas complicating infective endocarditis.
AB  - This study sought to determine the clinical and echocardiographic features,
      surgical approach, and outcome of patients with infective endocarditis
      complicated with aortocardiac fistulas among a series of 346 consecutive cases
      between 1988 and 1998. Nine patients (2%) were found to have aortocardiac
      fistulas complicating infective endocarditis caused by highly pyogenic pathogens
      (4 patients had ruptured abscesses of the right sinus of Valsalva, 3 had
      fistulous communications from the left coronary sinus, and 1 had a fistulized
      abscess in the noncoronary sinus). Mortality in these patients was very high
      (55%), even when surgery was attempted early in the course of the disease and
      reconstructive procedures were implemented.

PMID- 11230859
TI  - Mechanisms and immediate outcome of in-hospital cardiac arrest in patients with
      advanced heart failure secondary to ischemic or idiopathic dilated
      cardiomyopathy.
AB  - To differentiate patients with congestive heart failure who are more prone to
      develop malignant ventricular tachyarrhythmias or severe bradyarrhythmias as the
      terminal event, we retrospectively evaluated a group of 48 patients with advanced
      heart failure who experienced a monitored cardiac arrest during hospital stay. We
      found no significant differences with respect to several variables, apart from
      clinical status, which was worse in patients whose cardiac arrest was
      precipitated by severe bradycardia or electromechanical dissociation.

PMID- 11230860
TI  - Gianturco-Grifka vascular occlusion device for closure of patent ductus
      arteriosus.
AB  - We retrospectively reviewed the results of catheter closure of patent ductus
      areteriosus using the Ginaturco-Grifka vascular occlusion device in our
      institution. All patients in whom it was attempted had successful implantation,
      complete closure on follow-up, and no complications.

PMID- 11230861
TI  - Angiotensin-converting enzyme inhibitors in adults after the Mustard procedure.
AB  - Angiotensin-converting enzyme inhibitors had no significant effect on
      cardiopulmonary exercise function in 14 patients who had undergone a Mustard
      operation for transposition of the great arteries. In some patients aerobic
      capacity improved and maximum systolic blood pressure decreased.

PMID- 11230863
TI  - Usefulness of routine surveillance biopsies in children more than one year after
      orthotopic heart transplantation.
AB  - This retrospective study examines the usefulness of routine biopsies following
      the first year after transplant. This study found that routine biopsies detect
      few episodes of rejection in the first year after transplant and were less useful
      than nonroutine biopsies.

PMID- 11230862
TI  - Prevalence and relation to risk factors of carotid atherosclerosis and left
      ventricular hypertrophy in systemic lupus erythematosus and antiphospholipid
      antibody syndrome.
AB  - The prevalence of preclinical cardiovascular disease was determined in women with
      systemic lupus erythematosus (SLE) and control subjects matched for traditional
      risk factors. Compared with control subjects, patients with SLE had a higher
      prevalence of carotid atherosclerosis (41% vs 9%, p < 0.005) and left ventricular
      hypertrophy (32% vs 5%, p < 0.005), supporting the possibility that chronic
      inflammation predisposes to premature cardiovascular disease in SLE.

PMID- 11230864
TI  - Enhanced detection of right-to-left shunt through patent foramen ovale by
      transthoracic contrast echocardiography using harmonic imaging.
AB  - When the results of transesophageal echocardiography was regarded as the gold
      standard for detecting a patent foramen ovale (PFO) in 136 consecutive patients
      referred for evaluation of cardiac source of embolism, transthoracic harmonic
      imaging using saline contrast was superior to fundamental imaging in accuracy for
      detecting a PFO (sensitivity, 22.5%; specificity [p < 0.05] and sensitivity,
      100%; specificity 100%, respectively.)

PMID- 11230867
TI  - Overview of nicotinic receptors and their roles in the central nervous system.
AB  - Alzheimer's disease is a complex disorder affecting multiple neurotransmitters.
      In particular, the degenerative progression is associated with loss within the
      cholinergic systems. It should be anticipated that both muscarinic and nicotinic
      mechanisms are affected as cholinergic neurons are lost. This review focuses on
      the basic roles of neuronal nicotinic receptors, some subtypes of which decrease
      during Alzheimer's disease. Nicotinic acetylcholine receptors belong to a
      superfamily of ligand-gated ion channels that play key roles in synaptic
      transmission throughout the central nervous system. Neuronal nicotinic receptors,
      however, are not a single entity, but rather there are many different subtypes
      constructed from a variety of nicotinic subunit combinations. This structural
      diversity and the presynaptic, axonal, and postsynaptic locations of nicotinic
      receptors contribute to the varied roles these receptors play in the central
      nervous system. Presynaptic and preterminal nicotinic receptors enhance
      neurotransmitter release, and postsynaptic nicotinic receptors mediate a small
      minority of fast excitatory transmission. In addition, some nicotinic receptor
      subtypes have roles in synaptic plasticity and development. Nicotinic receptors
      are distributed to influence many neurotransmitter systems at more than one
      location, and the broad, but sparse, cholinergic innervation throughout the brain
      ensures that nicotinic acetylcholine receptors are important modulators of
      neuronal excitability.

PMID- 11230868
TI  - Nicotinic receptor abnormalities in Alzheimer's disease.
AB  - Loss of cortical nicotinic acetylcholine receptors with high affinity for
      agonists (20-50%) in patients with Alzheimer's disease is a common finding.
      Recent immunochemical analyses indicate that this deficit is predominantly
      associated with the loss of alpha4 subunits (30-50%), although modest reductions
      of alpha3 may occur in some individuals (25-29%). No reduction of beta2 subunit
      protein expression or levels of alpha3 and alpha4 messenger RNA has been
      reported. Decline in cortical [(125)I]alpha-bungarotoxin binding and alpha7
      protein expression does not appear to be as extensive or widespread as the loss
      of alpha4 (0-40%), with no reduction in messenger RNA expression. In the
      thalamus, there was a trend for reduced [(3)H]nicotine binding in the majority of
      nuclei (0-20%) in Alzheimer's disease; however, there was a significant decline
      in [(125)I]alpha-bungarotoxin binding in the reticular nucleus. In the striatum
      [(3)H]nicotine binding was reduced in Alzheimer's disease, and although
      neuroleptic medication accentuated this change, it occurred in those free of
      neuroleptics. Changes in nicotinic acetylcholine receptors in Alzheimer's disease
      are distinct from those in normal aging and are likely to contribute to clinical
      features and possibly neuropathology.

PMID- 11230869
TI  - Is there nicotinic modulation of nerve growth factor? Implications for
      cholinergic therapies in Alzheimer's disease.
AB  - Studies on the neurobiology of nerve growth factor (NGF) reveal a diverse range
      of actions. Through alterations in gene expression, NGF is important in
      maintaining and regulating the phenotype of neurons that express the high
      affinity receptor, trkA. Nerve growth factor also has a rapid action, revealed by
      its role in pain signaling in bladder and in skin. In the central nervous system
      (CNS), NGF has an intimate relationship with the cholinergic system. It promotes
      cholinergic neuron survival after experimental injury but also maintains and
      regulates the phenotype of uninjured cholinergic neurons. In addition to these
      effects mediated by gene expression, NGF has a rapid neurotransmitter-like action
      to regulate cholinergic neurotransmission and neuronal excitability. Consistent
      with its actions on the cholinergic system, NGF can enhance function in animals
      with cholinergic lesions and has been proposed to be useful in humans with
      Alzheimer's disease (AD); however, the problems of CNS delivery and of side
      effects (particularly pain) limit the clinical efficacy of NGF. Drug treatment
      strategies to enhance production of NGF in the CNS may be useful in the treatment
      of AD. Nicotine is one such agent, which, when administered directly to the
      hippocampus in rats, produces long-lasting elevation of NGF production.

PMID- 11230871
TI  - Nicotinic receptor abnormalities of Alzheimer's disease: therapeutic
      implications.
AB  - The neuronal nicotinic acetylcholine receptors (nAChRs) in the brain are
      important for functional processes, including cognitive and memory functions. The
      nAChRs acting as neuromodulators in communicative processes regulated by
      different neurotransmitters show a relatively high abundance in the human cortex,
      with a laminar distribution of the nAChRs of superhigh, high, and low affinity in
      the human cortex. The regional pattern of messenger RNA (mRNA) for various nAChR
      subtypes does not strictly follow the regional distribution of nAChR ligand
      binding sites in the human brain. Consistent losses of nAChRs have been measured
      in vitro in autopsy brain tissue of Alzheimer's disease patients (AD), as well as
      in vivo by positron emission tomography (PET). Measurement of the protein content
      of nAChRs showed reduced levels of the alpha4, alpha3, and alpha7 nAChR subtypes.
      The finding that the alpha4 and alpha3 mRNA levels were not changed in AD brains
      suggests that the losses in high-affinity nicotinic-binding sites cannot be
      attributed to alterations at the transcriptional level of the alpha4 and alpha3
      genes and that the causes have to be searched for at the translational and/or
      posttranslational level. The increased mRNA level of the alpha7 nAChR subtyep in
      the hippocampus indicates that subunit-specific changes in gene expression of the
      alpha7 nAChR might be associated with AD. The PET studies reveal deficits in
      nAChRs as an early phenomena in AD, stressing the importance of nAChRs as a
      potential target for drug intervention. PET ligands measuring the alpha4 nAChRs
      are under development. Studies of the influence of beta-amyloid on nAChRs in
      brain autopsy tissue from patients with the amyloid precursor protein 670/671
      mutation have shown that there is no direct relationship between nAChR deficits
      and pathology. Treatment with cholinergic drugs in AD patients indicate
      improvement of the nAChRs in the brain, as visualized by PET. Further studies on
      neuroprotective mechanisms mediated via nAChR subtypes are exciting new avenues.

PMID- 11230870
TI  - The association between smoking and Alzheimer's disease: effects of study design
      and bias.
AB  - In epidemiologic studies, unrecognized bias can contribute to observed results,
      causing them to be inaccurate. Analytic study designs, such as the case-control
      and cohort designs, each carry potential for specific forms of bias. The cohort
      design is not susceptible to many forms of bias that are experienced by case
      control studies. A consistent "protective" effect of smoking on Alzheimer's
      disease was documented by many case-control studies. However, the potential
      effect of biases cannot be separated from the results. Cohort studies now show
      that smoking may either be unrelated to Alzheimer's disease onset or possibly
      generate a modest increased risk. In this review the results and comparisons of
      various studies and potential biases are discussed.

PMID- 11230872
TI  - Imaging brain cholinergic activity with positron emission tomography: its role in
      the evaluation of cholinergic treatments in Alzheimer's dementia.
AB  - One of the strategies in the treatment of Alzheimer's disease is the use of drugs
      that enhance cholinergic brain function, since it is believed that cholinergic
      dysfunction is one of the factors that contributes to cognitive deterioration.
      Positron emission tomography is a medical imaging method that can be used to
      measure the concentration, kinetics, and distribution of cholinergic-enhancing
      drugs directly in the human brain and assess the effects of the drugs at markers
      of cholinergic cell viability (vesicular transporters, acetylcholinesterase), at
      muscarininc and nicotinic receptors, at extracellular acetylcholine, at markers
      of brain function (glucose metabolism and blood flow), and on amyloid plaque
      burden in vivo in the brains of patients with Alzheimer's disease. In addition,
      these measures can be applied to assess the drugs' pharmacokinetic and
      pharmacodynamic properties in the human brain. Since the studies are done in
      living human subjects, positron emission tomography can evaluate the relationship
      between the drugs' biological, behavioral, and cognitive effects; monitor changes
      in brain function in response to chronic treatment; and determine if
      pharmacologic interventions are neuroprotective. Moreover, because positron
      emission tomography has the potential to identify Alzheimer's disease during
      early disease, it can be used to establish whether early interventions can
      prevent or delay further development.

PMID- 11230873
TI  - Nicotine and its interaction with beta-amyloid protein: a short review.
AB  - Two features of Alzheimer's disease (AD) are beta-amyloid protein (betaAP)
      deposition and a severe cholinergic deficit. beta-Amyloid protein is a 39- to 43
      amino acid transmembrane fragment of a larger precursor molecule, amyloid
      precursor protein. It is a major constituent of senile plaque, a neuropathologic
      hallmark of AD, and has been shown to be neurotoxic in vivo and in vitro. The
      cholinergic neurotransmission system is seen as the primary target of AD.
      However, other systems are also found to show functional deficit. An association
      between cholinergic deficit and betaAP is suggested by a negative correlation
      between cigarette smoking and AD. Evidence hitherto suggests that betaAP causes
      neuronal death possibly via apoptosis by disrupting calcium homeostasis, which
      may involve direct activation or enhancement of ligand-gated or voltage-dependent
      calcium channels. Selective second messengers such as protein kinases are
      triggered that signal neuronal death. Nicotine or acetylcholinesterase inhibitors
      can partially prevent the neurotoxicity of betaAP in vivo and in vitro. However,
      the exact mechanism by which nicotine provides its protective effects is not
      fully understood, but clearly there are protective roles for nicotine. Here, some
      aspects of betaAP neurotoxicity and nicotinic intervention as a protective agent
      are discussed.

PMID- 11230874
TI  - Nicotinic receptor-mediated protection against beta-amyloid neurotoxicity.
AB  - Multiple lines of evidence, from molecular and cellular to epidemiologic, have
      implicated nicotinic transmission in the pathology of Alzheimer's disease. In
      this review we present evidence for nicotinic receptor-mediated protection
      against beta-amyloid and glutamate neurotoxicity, and the signal transduction
      involved in this mechanism. The data are based mainly on our studies using rat
      cultured primary neurons. Nicotine-induced protection was blocked by an alpha7
      nicotinic receptor antagonist, a phosphatidylinositol 3-kinase inhibitor, and an
      Src inhibitor. Levels of phosphorylated Akt, an effector of phosphatidylinositol
      3-kinase; Bcl-2; and Bcl-x were increased by nicotine administration. From these
      experimental data, our hypothesis for the mechanism of nicotinic receptor
      mediated survival signal transduction is that the alpha7 nicotinic receptor
      stimulates the Src family, which activates phosphatidylinositol 3-kinase to
      phosphorylate Akt, which subsequently transmits the signal to upregulate Bcl-2
      and Bcl-x. Upregulation of Bcl-2 and Bcl-x could prevent cells from neuronal
      death induced by beta-amyloid and glutamate. These findings suggest that an early
      diagnosis of Alzheimer's disease and protective therapy with nicotinic receptor
      stimulation could delay the progress of Alzheimer's disease.

PMID- 11230875
TI  - Effects of nicotine on APP secretion and Abeta- or CT(105)-induced toxicity.
AB  - Several lines of evidence indicated that overexpression or aberrant processing of
      amyloid precursor protein (APP) is causally related to Alzheimer's disease (AD).
      Amyloid precursor protein is principally cleaved within the amyloid beta protein
      domain to release a large soluble ectodomain (APPs), known to have a wide range
      of trophic functions. The central hypothesis guiding this review is that nicotine
      may play an important role in APP secretion and protection against toxicity
      induced by APP metabolic fragments (beta-amyloid [Abeta], carboxyl terminal
      [CT]). Findings from our experiments have shown that nicotine enhances the
      release of APPs, which has neurotrophic and neuroprotective activities in
      concentration-dependent (>50 micromol/L) and time-dependent (>2 hours) manners.
      In addition, pretreatment of nicotine (>10 micromol/L for 24 hours) partially
      prevented Abeta or CT(105)-induced cytotoxicity in primary cultured neuron cells,
      and the effects of nicotine-induced protection were inhibited by the pretreatment
      with a nicotine alpha-bungarotoxin. Nicotine (>10 micromol/L for 24 hours)
      partially inhibited CT(105)-induced cytotoxicity when PC12 cells was transfected
      with CT(105). From these results, we proposed that nicotine or nicotinic receptor
      agonist treatment might improve the cognitive functions not only by
      supplementation of cholinergic neurotransmission, but also by protecting Abeta-
      or CT(105)-induced neurotoxicity probably through the increased release of APPs
      and the activation of nicotinic receptors.

PMID- 11230876
TI  - Nicotine and amyloid formation.
AB  - The major protein constituents of amyloid deposits in Alzheimer's disease (AD)
      are the 40-residue beta-amyloid (Abeta) (1-40) peptide and the 42-residue Abeta(1
      42) peptide. The Abeta(1-42) is more pathogenic and produced in greater
      quantities in familial forms of AD. A major goal of research is to uncover a
      suitable inhibitor that either slows down or inhibits Abeta formation (beta
      amyloidosis). During beta-amyloidosis, structural changes associated with the
      conversion of monomeric Abeta peptide building blocks into the aggregated
      fibrillar beta-sheet structures occur (alpha-helix-->beta-sheet or random,
      extended chain-->beta-sheet). In previous work, we and others established that
      nicotine, a major component of cigarette smoke, inhibits beta-amyloidosis of the
      Abeta(1-42), which may result from nicotine binding to the alpha-helical
      structure. These conclusions were based on solution nuclear magnetic resonance
      (NMR) spectroscopic studies with the nonnative 28-residue Abeta(1-28). This
      information suggests that, when administered therapeutically to AD patients,
      nicotine may not only affect cholinergic activation, but could also conceivably
      alter amyloid deposition. In this report, NMR studies were augmented with the
      naturally occurring Abeta(1-42), under conditions where the peptide folds into a
      predominantly alpha-helical or random, extended chain structure. The major result
      is that nicotine shows only modest binding to these conformations, indicating
      that the nicotine inhibition to beta-amyloidosis probably results from binding to
      a small, soluble beta-sheet aggregate that is NMR invisible.

PMID- 11230877
TI  - Cognitive effects of nicotine.
AB  - Nicotine and other nicotinic agonists have been found to improve performance on
      attention and memory tasks. Clinical studies using nicotine skin patches have
      demonstrated the efficacy of nicotine in treating cognitive impairments
      associated with Alzheimer's disease, schizophrenia, and attention
      deficit/hyperactivity disorder. Experimental animal studies have demonstrated the
      persistence of nicotine-induced working memory improvement with chronic exposure,
      in addition to the efficacy of a variety of nicotinic agonists. Mechanistic
      studies have found that alpha7 and alpha4beta2 nicotinic receptors in the
      hippocampus are critical for nicotinic involvement in cognitive function.
      Clinical and experimental animal studies provide mutually supporting information
      for the development of novel nicotinic therapies for cognitive dysfunction.

PMID- 11230878
TI  - Nicotinic treatment of Alzheimer's disease.

PMID- 11230879
TI  - Allosteric sensitization of nicotinic receptors by galantamine, a new treatment
      strategy for Alzheimer's disease.
AB  - Cholinesterase inhibitors are the only approved drug treatment for patients with
      mild to moderately severe Alzheimer's disease. Interestingly, the clinical
      potency of these drugs does not correlate well with their activity as
      cholinesterase inhibitors, nor is their action as short lived as would be
      expected from purely symptomatic treatment. A few cholinesterase inhibitors,
      including galantamine, produce beneficial effects even after drug treatment has
      been terminated. These effects assume modes of action other than mere esterase
      inhibition and are capable of inducing systemic changes. We have recently
      discovered a mechanism that could account, at least in part, for the above
      mentioned unexpected properties of some cholinesterase inhibitors. We have found
      that a subgroup of cholinesterase inhibitors, including galantamine but excluding
      tacrine, directly interacts with nicotinic acetylcholine receptors. These
      compounds, named allosterically potentiating ligands, sensitize nicotinic
      receptors by increasing the probability of channel opening induced by
      acetylcholine and nicotinic agonists and by slowing down receptor
      desensitization. The allosterically potentiating ligand action, which is not
      necessarily associated with cholinesterase inhibition, has been demonstrated by
      whole-cell patch-clamp recordings to occur in natural murine and human neurons
      and in murine and human cell lines expressing various subtypes of neuronal
      nicotinic acetylcholine receptors.

PMID- 11230880
TI  - Galantamine, a cholinesterase inhibitor that allosterically modulates nicotinic
      receptors: effects on the course of Alzheimer's disease.
AB  - Despite the proven efficacy of acetylcholinesterase inhibitors in Alzheimer's
      disease, there is a need for new and more effective treatments. Galantamine is a
      novel treatment for Alzheimer's disease that inhibits acetylcholinesterase and
      modulates nicotinic receptors. In randomized, double-blind, placebo-controlled
      studies of up to 6 months duration, galantamine significantly improved cognitive
      function. Galantamine also had beneficial effects on instrumental and basic
      activities of daily living, and postponed the progression of behavioral symptoms.
      Patients who completed one of the 6-month, placebo-controlled studies were
      eligible to enter a 6-month, open-extension study of the 24-mg/day dose of
      galantamine. At the end of 12 months, cognitive function and activities of daily
      living were preserved in those patients who had been treated throughout the study
      with galantamine 24 mg/day. At 12 months, this group of patients had
      significantly better cognitive functions than patients who had been treated with
      a placebo for 6 months before receiving galantamine. These studies indicate that
      galantamine postpones the progression of symptoms in Alzheimer's disease. Since
      galantamine shows the greatest benefits when treatment is started early, its long
      term benefits may result from an effect on the underlying disease process; such
      an effect might be mediated by galantamine's concomitant action on nicotinic
      receptors.

PMID- 11230882
TI  - Radiobiological modelling of the treatment of leukaemia by total body
      irradiation.
AB  - PURPOSE: Total body irradiation (TBI) has been used as part of the conditioning
      regimen before bone marrow transplantation or stem cell re-infusion for more than
      30 years. A wide variety of regimens have been used, and no single one has
      emerged as the best. Experimental evidence suggests a diversity of
      radiosensitivities of leukaemia cells in culture, which may correlate with a
      significant variation of leukaemic cell radiosensitivities between patients. The
      purpose of this project was to compute leukaemic cell killing by different
      schedules and determine whether a "best treatment" could be devised for
      individual patients. METHODS: We have developed a mathematical model for
      leukaemic cell killing by alternative TBI schedules, applied to a patient
      population with diverse leukaemic radiosensitivities. We considered 13 schedules
      in clinical use, and 14 theoretical schedules calculated (by the linear-quadratic
      model) to be iso-effective for risk of radiation pneumonitis. When each schedule
      of treatment is applied to the patient population, a distribution of leukaemic
      cell kills (log cell kill values) can be obtained for that schedule. The
      leukaemic kill distribution was also computed for optimized individual
      scheduling, each individual being treated by the schedule that was most effective
      for that patient. Using available data on the clinically observed dose response
      relationship for acute myeloid leukaemia, the model was extended to provide
      leukaemia cure probabilities for each of the schedules and for the individualized
      strategy. RESULTS: The computer simulations show that each schedule, applied to
      the treatment of a radiobiologically diverse patient population, results in a
      broad distribution of leukaemic log kill values, with a mean of 3-5 for most
      schedules (i.e. 10(-3)-10(-5) surviving fraction of leukaemic cells), and a broad
      variation (1-10 log kill) amongst patients. The distributions generated by the
      various schedules were found to be overlapping, implying that many of the
      schedules would be difficult to distinguish reliably in clinical trials.
      Individualized optimum treatment is possible if radiobiological parameters are
      known for each patient and would improve the leukaemic log kill distribution by
      about 1 log on average, corresponding to an increase of leukaemia cure
      probability of several percent overall. For some individual patients, however,
      optimal scheduling could make a large difference to treatment outcome.
      CONCLUSIONS: The use of many different clinical treatment schedules may be
      continuing because outcomes are similar when these diverse schedules are applied
      to unselected patient populations. The measurement of individual leukaemic cell
      radiosensitivity would allow individualized scheduling, which could result in
      modest increases in overall curability, but substantial improvements in survival
      or duration of remission for individual patients.

PMID- 11230881
TI  - Effects of nicotine pretreatment on dopaminergic and behavioral responses to
      conditioned fear stress in rats: dissociation of biochemical and behavioral
      effects.
AB  - BACKGROUND: We have examined the effects of nicotine pretreatment on dopaminergic
      and behavioral responses to conditioned fear stress in the rat. METHODS: Rats
      were pretreated daily with saline or nicotine for 20 days then challenged with
      nicotine or saline on day 21. Animals were trained in a classical conditioned
      fear paradigm. Dopamine utilization in the medial prefrontal cortex and nucleus
      accumbens shell and conditioned fear stress-induced immobility responses were
      assessed. RESULTS: Saline pretreated animals rapidly acquired the conditioned
      fear stress response as assessed by preferential activation of mesoprefrontal
      dopamine metabolism and tone-elicited immobility responses. Repeated, but not
      acute, nicotine pretreatment significantly reduced conditioned fear stress
      induced dopamine metabolism in the medial prefrontal cortex and nucleus accumbens
      shell. Repeated nicotine pretreatment did not modify the acquisition or
      expression of conditioned fear stress responses, however. CONCLUSIONS: The
      dissimilar effects of repeated nicotine exposure on the cortical dopamine and
      behavioral responses to conditioned fear stress suggest that nicotine differs
      from other agents with anxiolytic activity that produce coordinated changes in
      conditioned fear stress-induced cortical dopaminergic and behavioral responses.
      Furthermore, compared with results of acute footshock stress, repeated nicotine
      pretreatment appears to have differential effects on physical versus
      psychological stressors. Results are discussed within the clinical context of
      stress-related psychopathology syndromes and comorbid nicotine dependence.

PMID- 11230883
TI  - Clinical indications and biological mechanisms of splenic irradiation in chronic
      leukaemias and myeloproliferative disorders.
AB  - Splenic irradiation (SI) was the first efficient treatment for chronic leukaemia,
      but with the emergence of effective drugs its use has been more and more
      restricted to advanced cases presenting with splenomegaly. But in selected
      patients who are not responsive or not suitable to drug treatment, SI may offer
      still an effective, low toxic and cost-effective palliative modality. Eight
      studies of SI in chronic lymphatic leukaemia (CLL) including 198 patients, six
      reports about SI in prolymphocytic leukaemia (PLL), including 18 patients, one
      study and six case reports about SI in hairy cell leukaemia (HCL) and nine
      studies about SI in myeloproliferative disorders has been analyzed. In CLL,
      symptoms of splenomegaly have been improved in 50-87% of all patients with
      overall doses between 4 and 10 Gy in mostly 1-Gy fractions. PLL seems to be more
      resistant to SI with a median response rate of 66%. Casuistic reports described
      also efficacy of SI in HCL patients using similar radiation schedules.
      Symptomatic relief is also provided by SI in myeloproliferative disorders using
      lower overall doses between 1 and 9 Gy with small single fractions of 0.25 Gy
      (median). Acute toxicity was low in lymphoid disorders, but higher in
      myeloproliferative disorders with severe cytopenia in 10-30% of all cases,
      indicating the need for a cautious fractionation schedule. Interestingly, even
      complete systemic remissions after SI in all types of lymphoproliferative
      disorders have been described. Different mechanisms underlying SI such as direct
      cell kill, immune modulation via changes in lymphocyte subsets or cytokine
      induction or "radiotherapeutic" splenectomy with high doses are discussed.

PMID- 11230884
TI  - Total body irradiation-based regimen in the conditioning of patients submitted to
      haploidentical stem cell transplantation.
AB  - BACKGROUND AND PURPOSE: To evaluate the efficacy and toxicity of a highly immuno-
      and myelo-suppressive conditioning regimen followed by the infusion of large
      numbers of T-cell-depleted mismatched haematopoietic stem cells in 43 high-risk
      acute leukaemia patients. RESULTS: A high rate of engraftment (95%) and no graft
      versus-host disease (GvHD) were observed. The 4-year probability of event-free
      survival was 0.25+/-0.09 for acute myeloid leukaemia and 0.17+/-0.07 for acute
      lymphoid leukaemia patients. CONCLUSIONS: This study shows that the main
      obstacles limiting the use of mismatched transplants, i.e. GvHD and rejection,
      were overcome.

PMID- 11230885
TI  - Cyclophosphamide, doxorubicin, vincristine and prednisone chemotherapy and
      radiotherapy for stage I intermediate or high grade non-Hodgkin's lymphomas:
      results of a strategy that adapts radiotherapy dose to the response after
      chemotherapy.
AB  - BACKGROUND: A limited number cycles of cyclophosphamide, doxorubicin, vincristine
      and prednisone (CHOP) chemotherapy followed by involved field radiotherapy is the
      treatment of choice for Ann Arbor stage I intermediate or high grade non
      Hodgkin's lymphomas (NHL). The optimal radiotherapy dose in this combined
      modality setting, resulting in maximal disease control with minimal toxicity is
      unknown. In this retrospective single-center study we evaluated the results of a
      combined modality treatment strategy that adapts the radiotherapy dose to the
      response after chemotherapy, and focus on the influence of radiotherapy dose on
      local control and survival. PATIENTS AND METHODS: One hundred and forty patients
      with NHL Ann Arbor stages I/IE of intermediate or high grade malignancy received
      four cycles of CHOP chemotherapy followed by involved field radiotherapy (IF-RT).
      The radiotherapy dose for patients in complete response (CR) after CHOP was
      either 26 or 40 Gy. Patients in partial response (PR) after CHOP always received
      40 Gy. The influence of the radiotherapy dose on treatment outcome was evaluated
      for patients in CR at the end of treatment (n=128). RESULTS: CR rates after
      chemotherapy and after radiotherapy were 67 and 91%, respectively. Seventy-four
      of the patients in CR after CHOP received 26 Gy, 20 patients in CR after CHOP 40
      Gy. All patients in PR after CHOP (n=34) received 40 Gy. The localization of
      relapse (within or outside the radiation field) did not differ between patients
      receiving 26 or 40 Gy. Overall survival (OS) at 5 years for patients in CR after
      CHOP who received 26 and 40 Gy and for patients in PR after CHOP but CR after 40
      Gy IF-RT was 76, 100 and 75%, respectively, (P=0.16), disease free survival (DFS)
      at 5 years 69, 90 and 75%, respectively, (P=0.52). CONCLUSIONS: No statistically
      significant differences in patterns of relapse or survival were found between
      patients receiving 26 or 40 Gy IF-RT, however the number of events in all
      subgroups was small.

PMID- 11230887
TI  - Bronchoscopically-guided conformal radiation therapy for radiographically occult
      lung carcinoma.
AB  - Radiographically occult lung carcinoma has a very good prognosis after complete
      surgical resection. In medically inoperable patients three-dimensional conformal
      radiation therapy cannot be performed, as computed tomography scan images fail to
      localize the disease. Presented here is an original technique of marking
      radiographically occult tumors by fiberoptic bronchoscopy, applied on four
      patients. No short-term complications were recorded. All the patients are alive,
      with no evidence of disease, after a mean follow-up of 15 months.

PMID- 11230886
TI  - External irradiation versus external irradiation plus endobronchial brachytherapy
      in inoperable non-small cell lung cancer: a prospective randomized study.
AB  - PURPOSE: No randomized studies are available on the additional value of
      endobronchial brachytherapy (EBB) to external irradiation (XRT) regarding
      palliation of respiratory symptoms (RS). A prospective randomized study was
      initiated to test the hypothesis that the addition of EBB to XRT provides higher
      levels of palliation of dyspnea and other RS and improvement of quality of life
      (QoL) in patients with non-small cell lung cancer (NSCLC) with endobronchial
      tumour. MATERIALS AND METHODS: Patients with previously untreated NSCLC, stages I
      IIIb, WHO-performance status of 0-3 and with biopsy proven endobronchial tumour
      in the proximal airways were eligible. EBB consisted of two fractions of 7.5 Gy
      at 1 cm on day 1 and 8. XRT started at day 2. The XRT dose was 30 Gy (2 weeks) or
      60 Gy (6 weeks). The EORTC QLQ-C30 and QLQ-LC13 were assessed before treatment
      and 2 weeks, 6 weeks, 3, 6 and 12 months after treatment. Re-expansion of
      collapsed lung was tested by the inspiratory vital capacity (IVC) and CT scan of
      the chest. RESULTS: Ninety-five patients were randomized between arm 1 (XRT
      alone) (n=48) or arm 2 (XRT+EBB) (n=47). The arms were well balanced regarding
      pre-treatment characteristics and QoL scores. The compliance for QoL-assessment
      was >90% at all times. No significant difference between the trial arms was
      observed with respect to response of dyspnea. However, a beneficial effect of EBB
      was noted concerning the mean scores of dyspnea over time (P=0.02), which lasted
      for 3 months. This benefit was only observed among patients with an obstructing
      tumour of the main bronchus. A higher rate of re-expansion of collapsed lung was
      observed in arm 2 (57%) compared to arm 1 (35%) (P=0.01). The inspiratory vital
      capacity (IVC) assessed 2 weeks after radiotherapy improved with 493 cm(3) in arm
      2 and decreased 50 cm(3) in arm 1 (P=0.03). No difference was noted regarding the
      incidence of massive haemoptysis (13 vs. 15%). CONCLUSION: The addition of EBB to
      XRT in NSCLC is safe and provides higher rates of re-expansion of collapsed lung
      resulting in a transient lower levels of dyspnea. This beneficial effect was only
      observed among patients with obstructing tumours in the main bronchus.

PMID- 11230888
TI  - Endoscopic findings of radiation esophagitis in concurrent chemoradiotherapy for
      intrathoracic malignancies.
AB  - BACKGROUND AND PURPOSE: The incidence and extent of radiation esophagitis were
      assessed endoscopically in patients treated with concurrent chemoradiotherapy.
      PATIENTS AND METHODS: Eighty-two patients who received thoracic radiotherapy for
      lung, thymic, or esophageal cancer were investigated endoscopically from July
      1991 to the end of 1997. Among them, 23 esophageal cancer patients were treated
      with radiation alone, and the others were treated with concurrent
      chemoradiotherapy. Esophageal endoscopy was performed during or just after
      radiotherapy. The presence of radiation esophagitis was assessed and assigned an
      endoscopic score (i.e. grade 0 for normal, 1 for erythema, 2 for erosion or
      sloughing, 3 for ulcer, hemorrhage, or stricture). The symptomatic grade was
      assessed using the RTOG (Radiation Therapy Oncology Group) acute radiation
      morbidity score. RESULTS: A correlation was seen between endoscopic and RTOG
      scores. However, even some patients with RTOG grade 0 to 1 had endoscopic grade 3
      esophagitis. Endoscopic grade 3 was observed in 16 (27.1%) patients in the
      concurrent chemoradiotherapy group, whereas it did not occur in any patient in
      the radiation alone group (P=0.004). CONCLUSIONS: Our results suggest that (1)
      RTOG score correlates closely to esophageal mucosal damage, and (2) more severe
      esophagitis occurs in those undergoing concurrent chemoradiotherapy than those
      undergoing radiotherapy alone [corrected].

PMID- 11230889
TI  - Double-blind randomized phase II study of hyperbaric oxygen in patients with
      radiation-induced brachial plexopathy.
AB  - BACKGROUND: Radiation-induced brachial plexopathy (RIBP) is an untreatable
      complication of curative radiotherapy for early breast cancer, characterized by
      chronic neuropathic pain and limb paralysis. Hyperbaric oxygen (HBO2) therapy is
      known to promote healing of tissue rendered ischaemic by radiotherapy, but is
      untested in RIBP. METHODS: Thirty four eligible research volunteers suffering
      from RIBP were randomized to HBO2 or control group. The HBO2 group breathed 100%
      oxygen for 100 min in a multiplace hyperbaric chamber on 30 occasions over a
      period of 6 weeks. The control group accompanied the HBO2 group and breathed a
      gas mixture equivalent to breathing 100% oxygen at surface pressure. All
      volunteers and investigators, except the operators of the hyperbaric chamber and
      the trial statistician, were blind to treatment assignments. The warm sensory
      threshold, which measures the function of small sensory fibres, was selected as
      the primary endpoint. FINDINGS: Pre-treatment neurophysiological tests were
      grossly abnormal in the affected hand compared to the unaffected hand in both
      HBO2 and control groups, as expected, but no statistically significant
      differences were noted in either group at any time up to 12 months post
      treatment. However, normalization of the warm sensory threshold in two of the
      HBO2 group was reliably recorded. Two cases with marked chronic arm lymphoedema
      reported major and persistent improvements in arm volume for at least 12 months
      after treatment with HBO2. IINTERPRETATION: There is no reliable evidence to
      support the hypothesis that HBO2 therapy slows or reverses RIBP in a substantial
      proportion of affected individuals, although improvements in warm sensory
      threshold offer some suggestion of therapeutic effect. Improvement in long
      standing arm lymphoedema was not anticipated, and justifies further
      investigation.

PMID- 11230890
TI  - Left sided vocal cord paralysis: a newly recognized late complication of
      mediastinal irradiation.
AB  - BACKGROUND AND PURPOSE: To evaluate the incidence of vocal cord paralysis in a
      group of breast cancer patients treated with post operative radiation therapy
      after radical mastectomy. MATERIALS AND METHODS: A group of 150 patients operated
      with total mastectomy and axillary clearance received, in 1963-1965, post
      operative radiotherapy to the parasternal, axillary and supraclavicular lymph
      node regions. The cohort has now been followed up to 34 years. RESULTS: Eleven of
      the 12 vocal cord paralyses were left sided, although the breast cancer was
      almost equally distributed as left- and right-sided (55 vs. 45%). The symptoms
      did not appear until 2-25 years after irradiation. Series 1 (treated with (60)Co
      photons) developed 5% recurrent nerve paralysis (RNP) after a median time of 19.0
      years compared with 10% and a much earlier appearance (3.5 years) for series 2
      (treated with both (60)Co photons and electrons). A reconstruction of the dose
      plan shows that an unintentional overlap of the fields resulted in hotspots in
      the tracheo-oesophageal groove, where parts of the tissue received 120-130% of
      the prescribed dose. CONCLUSIONS: A left-sided vocal cord paralysis of patients
      treated with mediastinal radiotherapy might not indicate only tumour recurrence
      but also mediastinal fibrosis. Small differences in patient positioning cannot be
      excluded as the cause of the difference in the two series. We postulate that
      other more subtle damage to the vagus nerve may occur without being recognized as
      late radiation injury.

PMID- 11230891
TI  - Circulating atrial natriuretic peptide plasma levels as a marker for cardiac
      damage after radiotherapy.
AB  - PURPOSE: To investigate whether plasma concentrations of atrial natriuretic
      peptide (ANP) could be used to identify patients with radiation mediated cardiac
      dysfunction. MATERIALS AND METHODS: Circulating levels of ANP were measured in
      patients who have been irradiated on a large part of the heart (50-80%; Hodgkin's
      disease) or smaller part of the heart (20-30%; primary breast cancer). C-terminal
      ANP was determined by radioimmunoassay (RIA) using a commercial kit. RESULTS: In
      this study ANP plasma levels of 121 patients (Hodgkin's disease, 73 patients;
      breast cancer, 48 patients) and 67 controls were examined. ANP plasma levels of
      both Hodgkin patients (28.8+/-2.2, P=0.003) and breast cancer patients (20.4+/
      2.8 ng/l, P=0.01) were significantly elevated when compared to age-matched
      controls (13.5+/-1.2 ng/l). Both for the Hodgkin (R=0.42, P=0.05) and breast
      cancer group (R=0.50, P=0.09) a positive relation between ANP plasma values and
      age was found. However, no clear relation between ANP plasma levels and time post
      treatment could be demonstrated. Patients with clinical symptoms of
      cardiovascular disease (n=25) had significantly higher ANP plasma levels
      (P<0.001) compared to patients in the same treatment group without evidence of
      cardiac disease (50.2+/-7.5 vs. 23.3+/-1.3 ng/l, P<0.001, and 38.2+/-12.4 vs.
      16.3+/-1.6 ng/l, P<0.001, for Hodgkin's disease and breast cancer, respectively).
      Eight patients suffered from essential hypertension (n=8), whereas the remaining
      group of 17 patients showed a variety of cardiac disorders (i.e. myocardial
      infarction, decreasing ventricular function, and atrial fibrillations). In 11
      patients cardiac problems were manifest either before or within a few years after
      mediastinal therapy. In two patients treated for Hodgkin's disease, and in four
      patients treated for breast cancer cardiac problems became manifest a long time
      (>10 years) after radiotherapy. Probably in this group of patients cardiac
      problems are related to the therapy. CONCLUSIONS: The present study indicates
      that ANP plasma levels could be used to identify patients with radiation induced
      cardiac dysfunction.

PMID- 11230892
TI  - Structural changes in the auricles of the rat heart after local ionizing
      irradiation.
AB  - BACKGROUND AND PURPOSE: Irradiation of the heart may lead to late cardiovascular
      complications and depending on the dose to cardiac-related death. There is
      increasing evidence that left atrial appendages play an important role in left
      ventricular filling especially in cardiac disease. The aim of the present study
      was to investigate the radiation response of the atria of the rat heart (auricles
      in particular) at morphological, histological and transcriptional level. MATERIAL
      AND METHODS: Sprague-Dawley rats were irradiated with a single dose locally on
      the heart (0-22.5 Gy). End-diastolic diameters of left auricles were measured
      during evaluation of cardiac function. Histopathological evaluations were
      performed at various time points up to 16 months post irradiation. Changes in
      mRNA expression of procollagen types I and III and pro-fibrogenic cytokines (TGF
      beta1 and IL-1beta) were investigated using competitive PCR. RESULTS: Irradiation
      leads to a dose-dependent decrease in end-diastolic diameter of the left
      auricles. This decrease was observed at 4 months post-irradiation, where no gross
      damage of the ventricle has been reported. Histologically, epicardial fibrosis
      was found already 1 month post irradiation, and the frequency/severity of the
      structural changes appeared to be dose-dependent and progressive with time post
      irradiation. At 9 months, fibrosis was observed in all three layers (epicardium,
      myocardium and endocardium) of both auricles. On the level of gene expression,
      increases in procollagen types I and III were observed at 12 and 3 months post
      irradiation, respectively. Increases in IL-1beta and TGF-beta1, cytokines known
      to influence collagen deposition at different levels, preceded the upregulation
      of procollagen mRNA. CONCLUSIONS: Auricles of the rat heart show a marked
      pathological response to ionizing radiation, characterized by generalized
      accumulation of collagen (fibrosis) and a reduction of end-diastolic diameter.
      The reduction of auricular volume and loss of elasticity will negatively
      contribute to the pump function of the irradiated ventricle.

PMID- 11230893
TI  - Comparison of three rat strains for development of radiation-induced lung injury
      after hemithoracic irradiation.
AB  - The purpose of this study is to define differences in radiation sensitivity among
      rat strains using breathing frequency and lung perfusion as end points of
      radiation-induced lung injury. The results have confirmed previous findings in
      mice showing that under stringently controlled iso-dose/volume irradiation
      conditions, substantial differences can be found in susceptibility to functional
      lung damage after radiation.

PMID- 11230894
TI  - Type I collagen turnover and cross-linking are increased in irradiated skin of
      breast cancer patients.
AB  - BACKGROUND AND PURPOSE: The effects of radiation therapy on the turnover and
      structure of type I collagen were studied in irradiated and contralateral skin of
      18 breast cancer patients without clinically evident fibrosis. MATERIALS AND
      METHODS: The rates of on-going type I collagen synthesis and degradation were
      assessed by the aminoterminal propeptide of type I procollagen (PINP) and by two
      different assays (ICTP and SP4) for the carboxyterminal telopeptide of type I
      collagen in the soluble tissue extracts, respectively. Also, TIMP-1, TIMP-2 and
      the MMP-2/TIMP-2 complex were measured in the tissue extracts. Insoluble skin
      matrices, containing the cross-linked type I collagen fibres, were heat-denatured
      and digested with trypsin. Then, the variants of the carboxyterminal telopeptide
      of type I collagen were separated by high performance liquid chromatography
      (HPLC). The major histidinohydroxylysinonorleucine (HHL)-cross-linked variant was
      quantified by the SP4 assay, and the minor pyridinoline analogue (PA)-cross
      linked telopeptide was quantified by the ICTP assay. RESULTS: Both the synthesis
      and degradation of type I collagen were increased (r=0.906; P<0.001) on the
      irradiated side, whereas the concentration of the MMP-2/TIMP-2 complex was
      decreased. In the insoluble tissue digests, the HHL-cross-linked telopeptides of
      type I collagen, also, when expressed/tissue hydroxyproline, were increased in
      the irradiated skin. TIMP-1, TIMP-2 or PA-cross-linked telopeptides of type I
      collagen showed no differences between the two sides. CONCLUSIONS: Radiotherapy
      induces a long-term increase in the turnover of type I collagen and leads to the
      accumulation of cross-linked type I collagen in skin.

PMID- 11230895
TI  - Cu/Zn superoxide dismutase modulates phenotypic changes in cultured fibroblasts
      from human skin with chronic radiotherapy damage.
AB  - PURPOSE: As we previously observed that bovine liposomal Cu/Zn SOD (LipSOD)
      reduces cutaneous radiation-induced fibrosis (RIF) in human therapeutic assays
      the mechanisms involved were investigated here by an in vitro study of the LipSOD
      effects on cellular antioxidant metabolism and regulation of matrix degradation.
      METHODS: Primary cultures of human fibroblasts harvested from normal or RIF skin
      were treated with various doses of LipSOD. Catalase, Cu/Zn and Mn SOD endogenous
      cell enzyme activities and protein amounts were assayed by polyacrylamide gel
      electrophoresis and western blotting. Gene expressions of tissue inhibitor of
      metalloproteinases (TIMP) and TGF-beta1 was investigated by northern blot
      analysis. RESULTS: A deficiency of endogenous Mn SOD, considered to favour cell
      proliferation, was observed in cultured RIF cell. The present study showed that
      bovine Cu/Zn SOD entered the cells. Exposure to LipSOD (a) enhanced endogenous Mn
      SOD activity and protein level, without changes of endogenous Cu/Zn SOD and
      catalase, and (b) significantly reduced TIMP and TGF-beta1 gene expression, in
      RIF cells. No changes in these parameters were noted in treated control skin
      fibroblasts. CONCLUSION: Modulation of RIF skin fibroblasts by LipSOD seems
      effective via indirect endogenous Mn SOD activation, which might explain the cell
      phenotype reversion observed. TIMP reduction accounts for the elimination of
      collagenase activity inhibition and the subsequent digestion of excess
      extracellular matrix deposition, as well as RIF reversibility in vivo. The
      reduction of TGF-beta1 expression might explain the breaking of maintaining
      fibrotic cell activation connected with this growth factor.

PMID- 11230896
TI  - The impact of skin washing with water and soap during breast irradiation: a
      randomized study.
AB  - BACKGROUND: The effect of washing the irradiated skin during radiotherapy for
      breast cancer is uncertain. The purpose of this study was to evaluate the impact
      of washing the breast skin with water and soap during radiotherapy on the
      intensity of acute skin toxicity. MATERIALS AND METHODS: Ninety-nine patients
      treated for breast cancer were prospectively randomized prior to receiving
      radiotherapy to the breast into two groups: (1), no washing was allowed during
      radiotherapy (49 patients); and (2), washing was allowed with water and soap (50
      patients). Acute toxicity was recorded according to the Radiation Therapy
      Oncology Group (RTOG) acute skin toxicity scale for each patient every week
      during radiotherapy and 1 month after the end of radiotherapy. Symptoms related
      to skin toxicity were scored by visual analogue scales at the same time
      intervals. Other data collected included sociodemographic data, characteristics
      related to the tumor and previous treatments, radiation technique, necessity for
      a second simulation due to loss of skin marks and treatment interruptions.
      RESULTS: In the non-washing group, the following maximum acute toxicity scores
      were observed: grade 0, 2%; grade 1, 41%; grade 2, 57%; grades 3 and 4, 0%. For
      the washing group, the scores were: grade 0, 0%; grade 1, 64%; grade 2, 34%;
      grade 3, 2%; and grade 4, 0%. Moist desquamation was seen in 33% of non-washing
      patients, but in only 14% of washing patients. The median scores of pain, itching
      and burning of the treated skin were higher in the non-washing group, although
      this was not statistically significant. In a multivariate analysis using logistic
      regression, acute skin toxicity was associated with the patient's weight,
      concomitant radiochemotherapy and hot spots on dosimetry, and there was a trend
      toward more acute skin toxicity in the non-washing group. CONCLUSION: Washing the
      irradiated skin during the course of radiotherapy for breast cancer is not
      associated with increased skin toxicity and should not be discouraged.

PMID- 11230898
TI  - Some effects of repeated handling and the use of a mask on stress responses in
      zebu cattle during restraint.
AB  - The objective of this investigation was to evaluate the effect of repeated
      handling and the use of a mask on the order of entry, temperament, cortisol
      concentration and heart and respiratory rates of Brahman cattle during restraint
      in a squeeze chute. In the first experiment, 18 cows were restrained in the chute
      for 10min on 19 test-days and blood samples were collected during five of the
      trials. Habituation to handling was reflected by a decrease in cortisol
      concentration as the study advanced (P<0.01). In the second experiment, conducted
      6 months later, animals were randomly allotted to two groups, alternating the use
      of a mask over test-days while restraining the cows in the chute for 3min.
      Respiratory and heart rates were measured at the beginning and end of each 3min
      trial. A blood sample was also taken at the end of each trial. Respiratory rates
      decreased while the animals were restrained and this decrease tended to be
      greater (P=0.09) when the animals were wearing masks (3.06) than when not
      (2.2breaths/min). Heart rates also decreased and more so for masked animals
      (10.6beats/min) than for non-masked (5.0, P<0.01). Cortisol values tended to be
      higher (9.9 versus 4.7ng/ml, P=0.08) when animals were restrained without a mask.
      Temperament scores were lower (P>0.01) when cows were masked and have a relative
      high correlation (r=0.58) with flight distance values, (P<0.05). Finally, the
      order of entrance was found consistent over test-days, (P<0.01). It is concluded
      that Brahman cattle: (a) habituate to repeat handling in a squeeze chute; (b) are
      less emotionally reactive when their eyes were covered during this process and
      (c) establish a repeatable order of entrance to the chute.

PMID- 11230897
TI  - An improved breast irradiation technique using three-dimensional geometrical
      information and intensity modulation.
AB  - BACKGROUND AND PURPOSE: In spite of the complex geometry of the breast, treatment
      planning for tangential breast irradiation is conventionally performed using two
      dimensional patient anatomy information. The purpose of this work was to develop
      a new technique which takes the three-dimensional (3D) patient geometry into
      account. MATERIALS AND METHODS: An intensity-modulated radiotherapy (IMRT)
      technique was developed based on the division of the tangential fields in four
      multi-leaf collimator (MLC) shaped segments. The shape of these segments was
      obtained from an equivalent path length map of the irradiated volume.
      Approximately 88% of the dose was delivered by two open fields covering the whole
      treated volume. Dose calculations for the IMRT technique and the conventional
      technique were performed for five patients, using computer tomography (CT) data
      and a 3D calculation algorithm. A planning target volume (PTV) and ipsilateral
      lung volume were delineated in these CT data. RESULTS: All patients showed
      similar equivalent path length patterns. Analysis of the dose distribution showed
      an improved dose distribution using the IMRT technique. The dose inhomogeneity in
      the PTV was 9.0% (range 6.4-11.4%) for the conventional and 7.6% (range 6.5
      10.3%) for the IMRT technique. The mean lung dose was reduced for the IMRT
      technique by approximately 10% compared with the conventional technique.
      CONCLUSION: A new breast irradiation technique has been developed which improves
      the dose homogeneity within the planning target volume and reduces the dose to
      the lung. Furthermore, the IMRT technique creates the possibility to improve the
      field matching in case of multiple field irradiations of the breast and lymph
      nodes.

PMID- 11230899
TI  - A note on the effects of calf stimuli on the response of Zebu cows to Synchro
      mate-B.
AB  - The effect of Synchro-mate-B (SMB) was measured on the estrous response and the
      establishment of cyclicity using different calf stimuli. Multiparous Zebu cows,
      were divided in three groups. In the first, 32 animals were treated with SMB
      leaving the calves present (SMB+CP). In the second, 33 cows were treated with SMB
      and calves partially removed (fence-line contact) for 48h (SMB+CPR). In the third
      group (n=33), cows received SMB and calves were removed for 48h (SMB+CCR) with no
      visual or olfactory contact. A control group (CG, n=33) involved neither SMB or
      calf separation. Blood samples for progesterone assessment were obtained at 11
      and 4d prior to SMB treatment and on days 7 and 11 after the average return to
      estrous for each group. All animals were observed continuously for mounting
      activity during 72h after SMB implant removal. A significant difference (P<0.05)
      in estrous response was found between SMB-treated and non-treated animals,
      regardless of calf management (56 versus 8%, respectively). Cows with SMB+CCR and
      SMB+CPR came into estrous sooner (P<0.05) (26.5+/-2.6 and 18.1+/-4.94h,
      respectively), than those that remained with their calf present (40.4+/-12.8h).
      Cows with SMB+CCR displayed longer (P<0.05) periods of mounting behavior (13.0+/
      4.4h) in comparison with SMB+CPR and SMB+CP (7.4+/-1.8 and 8.1+/-4.0h),
      respectively. Furthermore, 84% (P<0.05) of the cows in the SMB+CCR had high
      concentrations of progesterone after mounting behavior was displayed, in
      comparison with 68 and 54% in the other two groups, respectively. No difference
      was found (P>0.05) in the number of mounts per hour in estrous. It was concluded
      that: (1) SMB increases the number of cows that display estrous; (2) temporary
      weaning shortens the period from SMB implant withdrawal to mounting activity, and
      (3) SMB+CCR, increases the length of sexual receptivity and the number of cows
      that continue to cycle.

PMID- 11230900
TI  - Cattle vocalizations are associated with handling and equipment problems at beef
      slaughter plants.
AB  - Vocalization of cattle in commercial slaughter plants is associated with
      observable aversive events such as prodding with electric prods, slipping in the
      stunning box, missed stuns, sharp edges on equipment or excessive pressure form a
      restraint device. A total of 5806 cattle were observed during handling and
      stunning in 48 commercial slaughter plants in the United States, Canada and
      Australia during the calendar year of 1999. Each animal was scored as either a
      vocalizer or a non-vocalizer. In 20 plants (42%), 0-1% of the cattle vocalized,
      in 12 plants (25%) 2-3% vocalized, in 12 plants (25%) 4-10% vocalized and in four
      plants (8%) more than 10% vocalized. In three plants repeated use of an electric
      prod on 95% or more of the cattle that balked and refused to move was associated
      with vocalization percentages of 17, 16 and 12%. In five plants, the percentage
      of cattle that vocalized was reduced by making modifications to plant equipment.
      Reducing the voltage on a rheostat controlled electric prod reduced the
      vocalization percentage from 7 to 2% in the first plant. In three other plants,
      the incidence of cattle backing up and balking was reduced by illuminating a dark
      entrance or adding a false floor to a conveyor restrainer. A false floor
      eliminates the visual cliff effect. The percentage of cattle that vocalized was
      reduced from 8 to 0%, 9 to 0% and 17 to 2%. Since balking was reduced, electric
      prod use was also reduced. In the fifth plant, reduction of the pressure exerted
      by a neck restraint reduced the percentage of cattle that vocalized from 23 to
      0%. In the five plants where modifications were made, a total of 379 cattle were
      observed prior to equipment modifications and 342 after modification. The mean
      percentage of cattle that vocalized was 12.8% before the modifications and 0.8%
      after the modifications (P<0.001). Vocalization scoring can be used to identify
      handling and equipment problems that may compromise animal welfare.

PMID- 11230901
TI  - The effect of parity and environmental restriction on behavioural and
      physiological responses of pre-parturient pigs.
AB  - There is increasing evidence that restriction of pre-parturient behaviour in pigs
      is stress-inducing, characterised by an elevation in hypothalamic-pituitary
      adrenal (HPA) activity in gilts. To determine whether pigs adapt to behavioural
      restriction, through modification of nest-building behaviour, we studied pre
      parturient pigs in either farrowing crates (no bedding, n=7) or straw-bedded pens
      (n=7) in their first (gilts) and second (sows) parity, with physiological
      measurements being taken in the second parity. Observations and blood sampling
      were carried out during the pre-parturient phase. Crated pigs changed posture
      more often than penned pigs (F(1,12)=7.06, P<0.05), with the number of posture
      changes reducing across parities in both environments. The reduction in posture
      changing was more apparent in the crated sows which may indicate that attempted
      nest-building behaviour of sows with prior experience of farrowing crates is less
      fragmented. The crated pigs spent a greater proportion of time sitting across
      both parities (F(1,12)=9.4, P<0.01), and spent less time manipulating available
      substrates (F(1,12)=10.67, P<0.05). There was a tendency for penned pigs to spend
      a greater proportion of time standing (F(1,12)=3.77, P=0.076) with peak nesting
      behaviour occurring earlier in relation to parturition than in crated pigs. In
      addition penned sows performed more floor-directed behaviour than penned gilts,
      and at an earlier stage in relation to parturition. However, crated sows also
      performed peak nest-building earlier than crated gilts. Plasma cortisol profiles
      indicated elevated HPA activity in crated sows during the pre-parturient period
      (F(42,303)=1.43, P<0.05) suggesting increased physiological stress, however, the
      difference between crated and penned sows was less than that previously seen in
      gilts. The increased range of pre-parturient behaviours seen in the penned sows
      suggests that experience may result in an 'improvement' in their nest-building
      behaviour: earlier preparation of the nest site and then subsequent manipulation
      of substrates. The crated sows appeared to show some behavioural adaptation to
      the crate environment; earlier peak in floor directed behaviour and total
      substrate directed behaviour, reduced posture changing. In conclusion the nest
      building behaviour of pigs is modified over parities with adaptation to the
      behavioural restrictions imposed by the farrowing crate. However, this
      adaptation, through prior experience, does not completely reduce the elevation in
      HPA activity previously reported in pre-parturient crated gilts.

PMID- 11230902
TI  - Can one unrestricted meal buffer the effects of previous pre-meal intervals on
      the feeding behaviour of sheep?
AB  - Varying the time since the last meal is one means of manipulating feeding
      motivation. In order to use this method effectively it is necessary to know
      whether and the extent to which effects of one pre-meal interval are carried over
      to affect the behaviour during the following meals. Pre-meal interval (PMI) is
      defined here for practical purposes, for short meals, as the time between the
      start of two successive meals. The possibility that one unrestricted meal might
      buffer the effects of an 8h as opposed to a 4h PMI on aspects of feeding
      behaviour was studied with eight Scottish Blackface sheep. They were fed on a
      regime in which they were given access to food until they finished their meal and
      lay down (this always occurred within 60min) at which time the remaining food was
      withdrawn. Feeding behaviour was recorded during the meal after these 4 and 8h
      intervals, as well as during the following meal 4h later.At a meal after a PMI of
      8h, compared to 4h, sheep had a higher intake per meal (mean+/-S.T.D. for 8 and
      4h PMI, respectively: 604.4+/-78.8 and 430.1+/-100.9g; P<0.001), a longer meal
      duration (27.1+/-7.5 and 21.8+/-8.1min; P<0.001), and a tendency for a higher
      intake rate (23.8+/-6.2 and 21.9+/-8.2g/min; P=0.11). During the following meal
      4h later these differences were smaller, but intake per meal still tended to be
      higher (430.8+/-81.5 and 338.5+/-45.6g; P<0.06) for sheep who had previously had
      the 8h PMI. Meal duration (21.9+/-7.2 and 20.6+/-7.08min; P=0.28) and intake rate
      (21.2+/-6.1 and 18.7+/-7.2g/min; P=0.13) were no longer different.A single meal
      after the different PMIs reduced differences in all three aspects of feeding
      behaviour observed during the subsequent meal, 4h later, but differences in
      intake per meal were still apparent. It is suggested that an additional meal may
      overcome the carry-over effect.

PMID- 11230903
TI  - Divergent selection on feather pecking behaviour in laying hens (Gallus gallus
      domesticus).
AB  - A selection experiment was initiated in 1996 in which selection for (HP line) and
      against (LP line) feather pecking was performed. The foundation stock was a White
      Leghorn layer strain established in 1970 and maintained since then as a random
      bred control line at the Institute. Six hatches were produced over three
      generations. At the age of 68 weeks (generation 0, 1996), 35 weeks (generation 1,
      1997), 30 weeks (generation 2, 1998), and 27 weeks (generation 3, 1999) female
      birds were transferred to observation pens and their feather pecking behaviour
      was recorded. In each generation, 30 females and 8 males were selected from
      approximately 200 females and 60 males. The selection criterion was breeding
      value estimated by animal model on the trait 'number of bouts of feather pecking
      per bird per hour'.Feather pecking behaviour in adult hens was significantly
      higher in HP than in LP. In generation 2 the following was recorded: 3.10 versus
      1.37 bouts per bird per hour (P<0.01), 7.04 versus 3.58 pecks per bird per hour
      (P<0.05) and the proportion of hens recorded feather pecking in the 180min
      observation period was 67 versus 56% (P<0.05). In generation 3 the following was
      recorded: 4.56 versus 0.63 bouts per bird per hour (P<0.001), 13.9 versus 2.51
      pecks per bird per hour (P<0.001) and the proportion of hens recorded feather
      pecking in the 180min observation period was 75 versus 49% (P<0.001).In
      generation 3, plumage condition was better in LP on neck, breast, back, wings and
      tail, as well as overall (P<0.001). Body weight did not differ between lines in
      generation 2, but in generation 3, HP hens were on average heavier than LP hens
      at the age of 27 weeks (1435g versus 1371g, P<0.001).

PMID- 11230904
TI  - Cognitive abilities - the result of selective pressures on food acquisition?
AB  - Locating and capturing food are suggested as significant selection pressures for
      the evolution of various cognitive abilities in mammals and birds. The hypothesis
      is proposed that aspects of food procuring behaviour should be strongly
      indicative of particular cognitive abilities.Experimental data concerning higher
      mental abilities in mammals and birds are reviewed. These data deal with self
      recognition studies, rule-learning experiments, number concept, deceptive
      abilities, tool-use and observational learning.A Darwinian approach reveals: (1)
      the adaptiveness of particular abilities for particular niches, (2) that in
      complex foraging environments, increases in foraging efficiencies in animals
      should result from the evolution of particular cognitive abilities, (3) that
      phenomena such as convergent mental evolution should be expected to have taken
      place across taxonomic groups for species exploiting similar niches, (4) that
      divergence in mental ability should also have taken place where related species
      have exploited dissimilar niches.Experimental data of higher mental abilities in
      animals concur with a Darwinian explanation for the distribution of these
      cognitive abilities and no anomalies have been found.There are, as a consequence,
      significant implications for the welfare of animals subject to training when
      training methodology gives little or no consideration to the various mental
      abilities of species.

PMID- 11230905
TI  - Reforming the Israeli health system: findings of a 3-year evaluation.
AB  - Israel, like many other European countries, has recently reformed its health care
      system. The regulated market created by the National Health Insurance (NHI) law
      embodies many of the principles of managed competition. The purpose of this paper
      is to present initial findings from an evaluation of the first 3 years of the
      reform (1995-1997) regarding the implementation of the reform and the extent to
      which it has achieved its main goals. The evaluation was conducted using multiple
      quantitative and qualitative research tools: interviews with key informants;
      analysis of documents and sick fund financial statements; analysis of trends in
      sick fund membership; and population surveys conducted in 1995 and 1997 to assess
      the impact of the reform on outcome measures related to level of services to the
      public. Data from the evaluation show that the NHI law achieved a considerable
      number of its goals: to provide insurance coverage for the entire population, to
      ensure freedom of movement among sick funds, and to standardize the way resources
      are allocated to sick funds. The incentives that are embodied in the law have
      encouraged the sick funds to improve the level of services provided to the
      average insuree, and to develop services in the periphery and for some of the
      weaker populations. From the financial perspective, concerns that NHI would lead
      to a rise in the national health expenditure were not realized as of 1997. In the
      wake of NHI, there has been a decline in the age adjusted per capita expenditure
      in three sick funds, with no reports by insurees, at least through 1997, on a
      decline in satisfaction or level of service. However, the Israeli experience
      shows that regulating competition does not necessarily lead to economic stability
      and equality. Regulating the competition also did not solve some of the major
      policy issues in the Israeli health system including level of resources allocated
      to health, organizational structure of the hospital system, manpower planning and
      the extent of government involvement in system. Additional policy changes may be
      needed to resolve these issues. Up-to-date information is essential in helping
      policymakers track the process of reform implementation and results, and identify
      problems which need to be addressed in the future.

PMID- 11230906
TI  - Assessing efficiency in the UK breast screening programme: does size of screening
      unit make a difference?
AB  - The UK breast screening programme (UK BSP) is organised into a large number of
      individual screening units. Decision makers need to ensure these units are
      producing efficiently, particularly as the programme is anticipated to expand.
      Data envelopment analysis (DEA) was applied to investigate: the relative
      efficiency of screening units; the impact of screening unit size on efficiency;
      and how individual units could improve. Sixty-four screening units were
      categorised into 33 large and 31 small. Data were collected using a national
      survey and routinely collected data. The overall median efficiency score was 91%,
      39 units were inefficient. Variation in efficiency scores was wide. Large units
      had a median efficiency score of 100% and 12 units were inefficient. Smaller
      units had a median efficiency score of 95% and 19 were inefficient. This
      difference was not statistically significant (Mann-Whitney, P=0.076). Forty-two
      percent of large units and 21% of small units were operating at constant returns
      to scale (mean difference 0.20, 95% CI: 0.15-0.43). Although there is no
      systematic difference in efficiency by size of screening unit there are
      inefficiencies in both large and small units and there is scope for many
      individual units to improve their use of current resources. It will be necessary
      for decision-makers to examine the practices of individual screening units before
      considering options for how best to improve their resource use. DEA can help to
      identify feasible options.

PMID- 11230907
TI  - Support and consultation for general practitioners concerning euthanasia: the
      SCEA project. Support and Consultation in Euthanasia in Amsterdam.
AB  - In the project 'Support and consultation in Euthanasia in Amsterdam' (SCEA)
      general practitioners can turn to 20 especially trained physicians for advice or
      consultation concerning euthanasia or physician-assisted suicide. In this study
      the implementation was evaluated and it was investigated whether the goals of
      SCEA, supporting physicians and improving the quality of consultation, the
      quality of decision-making and the willingness to report, were met. Methods used
      were a questionnaire send to all general practitioners registered in Amsterdam
      (n=398), registration forms SCEA physicians filled in for every time SCEA was
      contacted and records of the public prosecutor. After the study period of 14
      months, of the general practitioners who had performed euthanasia during this
      period, 53% had contacted SCEA at least once. The vast majority of general
      practitioners felt supported by SCEA. The quality of consultation was (even)
      higher in cases of euthanasia in which a SCEA physician acted as consultant than
      in cases with another consultant. We found no relation between use of SCEA and
      the last two goals of SCEA. CONCLUSIONS: Whether the lack of relation found
      between SCEA and it's last two goals is real or due to the studies limitations
      remains unclear. The results of this study do suggest that SCEA, by further
      improving the quality of consultation, has contributed to the safeguarding of
      euthanasia and assisted suicide. Therefore, similar networks are being developed
      throughout the Netherlands.

PMID- 11230908
TI  - Reimbursement policies, incentives and disincentives to perform laparoscopic
      surgery in Israel.
AB  - The introduction of laparoscopic surgery was believed to bestow great advantages
      to patients and health services. Health services and societal costs may also be
      affected by changes in length of hospital stay, operating room costs and return
      to normal activity. The aim of this paper is to examine the influence of two
      different reimbursement methods (per diem and DRG) on the incentives and
      disincentives given to different role players in the Israeli health-care system
      regarding two common surgical procedures: appendectomy and inguinal hernia
      repair. Three different perspectives are discussed: society, the hospitals and
      the sick funds. From the hospital's perspective, laparoscopic surgery is usually
      more expensive compared to open procedures, mainly due to higher operating room
      costs. We suggest that as far as current reimbursement methods are preserved,
      hospitals have no economic incentive to adopt the laparoscopic technology as
      benefits occur only to society. In general, sick funds would encourage hospitals
      to perform laparoscopic appendectomy, where the payment is per diem and would be
      economically indifferent regarding laparoscopic inguinal hernia repair, where
      hospitals are compensated on a DRG basis. It has been suggested that economic
      advantages to society may arise from a faster return to work after laparoscopic
      appendectomy and laparoscopic inguinal hernia repair. In this case, new payment
      arrangements should be set to give proper incentives for the adoption of
      laparoscopic procedures.

PMID- 11230909
TI  - Adoption of new health care services in Norway (1993-1997): specialists' self
      assessment according to national criteria for priority setting.
AB  - OBJECTIVES: To identify health care services adopted in Norway in the period 1993
      1997, and examine them according to proposed national guidelines for priority
      setting. These guidelines define core services. DESIGN: Two-stage self
      administered questionnaire. SETTING: The Norwegian public healthcare system.
      SUBJECTS: Presidents of all relevant specialist and sub-specialist associations
      in the Norwegian Medical Association (n=56). OUTCOME MEASURES: Number of adopted
      services satisfying the priority criteria of core services, according to
      physician's self-assessment. Number and type of interventions suited for the
      priority-setting criteria. RESULTS: Thirty-two percent of new technologies
      satisfied the definition of core services according to specialists' own
      assessment. Of the 88 responses analysed for the second stage of our survey,
      fifteen answers (17%) indicated lack of applicability of the priority setting
      criteria. Loss of applicability was related to diagnostic and procedure-related
      technologies. CONCLUSIONS: Less than one-half of the assessed technologies
      adopted in Norway in the period 1993-1997 satisfy proposed national criteria for
      priority setting. The guidelines are applicable for most interventions, but fail
      in most evaluations of diagnostic and procedure-related improvements. Independent
      and systematic evaluations of new technologies are needed within the context of
      priority setting.

PMID- 11230910
TI  - Application of a predictive Bayesian model to environmental accounting.
AB  - Environmental accounting techniques are intended to capture important
      environmental costs and benefits that are often overlooked in standard accounting
      practices. Environmental accounting methods themselves often ignore or
      inadequately represent large but highly uncertain environmental costs and costs
      conditioned by specific prior events. Use of a predictive Bayesian model is
      demonstrated for the assessment of such highly uncertain environmental and
      contingent costs. The predictive Bayesian approach presented generates
      probability distributions for the quantity of interest (rather than parameters
      thereof). A spreadsheet implementation of a previously proposed predictive
      Bayesian model, extended to represent contingent costs, is described and used to
      evaluate whether a firm should undertake an accelerated phase-out of its PCB
      containing transformers. Variability and uncertainty (due to lack of information)
      in transformer accident frequency and severity are assessed simultaneously using
      a combination of historical accident data, engineering model-based cost
      estimates, and subjective judgement. Model results are compared using several
      different risk measures. Use of the model for incorporation of environmental risk
      management into a company's overall risk management strategy is discussed.

PMID- 11230911
TI  - Prediction of flammability of gases by using F-number analysis.
AB  - A novel method of predicting flammability limits has been proposed. This method
      utilizes a new flammability index called F-number. For this purpose, an empirical
      expression of F-number has been derived to account for the flammability
      characteristics of various organic substances. The analysis has been done by
      fitting to the observed values of F-number for a wide variety of organic gases
      and vapors. As a result, it has been found that F-number is an excellent tool to
      analyze the flammability characteristics of various substances. It has also been
      shown that the values of upper and lower flammability limits can be derived from
      F-number together with the stoichiometric concentration corrected for the effect
      of selective diffusion.

PMID- 11230912
TI  - Discrepancies between different response parameters in batch and continuous algal
      toxicity tests.
AB  - The test sensitivities and reproducibilities based on different response
      endpoints (cell density and total cell volume) were compared using both bath and
      continuous algal toxicity tests. Parameters related to algal cell density are
      found to be more sensitive and reproducible than total cell volume which bears a
      direct correlation to algal biomass or dry weight. The magnitude of differences
      in the median effective concentration values could be upto six folds. The main
      cause for the above discrepancies is because the cell density and total cell
      volume are two response endpoints reflecting the degree of inhibition on the
      binary fission mechanism and overall photosynthesis, respectively. At low
      toxicant concentrations, the inhibitory effect is primarily on the cell division
      rather than on the cellular photosynthesis. Thus, more severe toxic effects are
      expected to be observed based on the cell density than the total cell volume. The
      results of this study clearly demonstrate that sensitivity and reproducibility
      can be significantly improved if response parameters are calculated based on the
      cell density. Traditionally, cell density data are often converted into biomass
      before assessing the effects of toxicants. This procedure may not be necessary
      and may reduce the test sensitivity.

PMID- 11230913
TI  - Separation of critical radioactive and non-radioactive species from aqueous waste
      streams.
AB  - The separation of radioactive and non-radioactive species from the simulated DOE
      neutralized current acid waste (NCAW) stream was studied. Cation and anion
      species were referred to their possible basic compounds, and divided into seven
      groups (nitrate, phosphate, sulfate, fluoride, nitrite, carbonate, and
      hydroxide). The nitrate group (the major anion in the DOE waste streams) contains
      several cations species, while the rest of the groups are only in the form of
      sodium. The precipitation measurements were conducted in three experimental
      stages. In the first stage, the precipitation of sodium sulfate, sodium
      phosphate, sodium-sulfate-phosphate, and aluminum nitrate systems were studied
      using isopropylamine (IPA) as a precipitation solvent. The objectives of this
      stage were to evaluate the precipitation ability of IPA in precipitating these
      compounds individually, and to validate the consistency of the analytical
      instruments and the employed experimental procedure. Tests performed on the
      acquired data indicated a high level of experimental consistency. The removal of
      phosphate, sulfate and aluminum were very high. In the second stage, the
      precipitation studies were conducted on the: (1) nitrate group alone; (2) binary
      groups containing the groups of nitrate-phosphate, nitrate-sulfate, nitrate
      fluoride, nitrate-nitrite, and nitrate-carbonate; (3) combined nitrate,
      phosphate, sulfate, and fluoride groups and (4) combined nitrate, phosphate,
      sulfate, fluoride, nitrite, and carbonate groups. IPA was used as a precipitation
      solvent. The objectives of this stage were to evaluate the interactions of these
      groups in the absence of the hydroxide group (e.g. DOE acid-dissolved sludge and
      acidified supernate streams), and the influence of such interactions on the
      individual removal of the targeted species. The removal of the aluminum,
      phosphate, fluoride, and alkaline cations were significantly high (reached
      99.9%). The removal of sulfate were moderately high (reached 87%), and the
      removal of nitrate and alkali cations including cesium were to some extent low
      (reached about 50%). In the third stage, the precipitation of inorganic species
      from the simulated NCAW stream was studied using IPA and ethylamine (EA). The
      precipitation process is very feasible for reducing the radioactivity contents of
      alkaline cations. However, the process is less effective in separating alkali
      cations including cesium. The removal of polyvalent transition metals such as
      aluminum ion is negatively influenced by the significant presence of hydroxide.
      While the process is effectively capable of separating phosphate, fluoride, and
      sulfate, it is significantly less effective in separating nitrate and nitrite. A
      previously derived thermodynamics framework was used to model the precipitation
      measurements. The framework provided two predictive equations (the 2-Suffix and 3
      Suffix equations). Both equations were reasonably adequate for predicting the
      solubility phase behavior of tested inorganic species in a mixed-solvents mixture
      as well as for estimating optimum interaction parameters. However, the 3-Suffix
      equation was better than the 2-Suffix equation. The parameters were useful for
      estimating the: (1) precipitation fractions (%P) of the studied species, for
      instance, at different concentration levels of similar targeted species, or in
      different waste streams with similar or approximate abundance of species, or at
      different solvents volume ratio (V(r)) where no experimental data are available.

PMID- 11230914
TI  - Solidification/stabilization of electric arc furnace dust using coal fly ash.
      Analysis of the stabilization process.
AB  - In this paper, the stabilization of electric arc furnace (EAF) dust containing
      hazardous metals such as Pb, Cd, Cr or Zn is described. The treatment involves a
      waste solidification/stabilization (S/S) process, using coal fly ash as the
      fundamental raw material and main binder. The article also contains a brief
      review of the most important recent publications related to the use of fly ash as
      S/S agents. The efficacy of the process has been evaluated mainly through
      leaching tests on the solidified products and compliance with some imposed
      leachate limits. The concentration of metals leaching from the S/S products was
      strongly leachate pH dependent; thus, the final pH of the leachate is the most
      important variable in reaching the limits and, therefore, in meeting the
      stabilization goals. In this study, the dependence relationship between the
      leachate pH and the concentrations of metals in the leachate are analyzed; in
      some cases, this allows us to estimate the speciation of contaminants in the S/S
      solids and to understand the mechanism responsible for reduced leachability of
      heavy metals from solidified wastes.

PMID- 11230916
TI  - Drug resistance in pathogenic African trypanosomes: what hopes for the future?
AB  - Trypanosomosis is a serious threat to both man and animals mostly in Africa.
      Although the first pathogenic trypanosome was discovered over a hundred years
      ago, there is still no prospect for effective control or eradication of the
      disease through the development and use of vaccines because of the phenomenon of
      antigenic variation. Control continues to rely heavily on chemotherapy and vector
      control strategies. This therapy and prophylaxis depends on the use of drugs
      which, apart from having been developed over 5 decades ago, suffer from such
      limitations as toxicity and with their continued use, drug resistance. Resistance
      to currently used drugs is a serious problem in most fields of anti-microbial
      chemotherapy, particularly in the case of trypanosomosis where resistance and
      cross-resistance in animals and man have been developing rapidly. The frequently
      and widely reported decreasing efficiency of available trypanocides, difficulties
      of sustaining tsetse control and little hope that a conventional, anti
      trypanosome vaccine will be produced in the near future, increase the imperative
      need for new drugs and alternative effective ways for the control of
      trypanosomosis. This review examines aspects of drug resistance in pathogenic
      trypanosomes, measures to minimise it, areas of future research in new drug
      targets and alternative control strategies. Based on these, it is our opinion
      that for now the management and control of trypanosomosis will continue to depend
      on proper usage of the few available trypanocides, especially strategic
      deployment of the sanative drugs in order to reduce the development of drug
      resistance, in addition to the continued use of environmentally friendly vector
      control programmes such tsetse trapping.

PMID- 11230915
TI  - Field monitoring and performance evaluation of a field-scale in-well aeration
      system at a gasoline-contaminated site.
AB  - Several in-well aeration (IWA) technologies have been used since the early 1990s,
      but few field studies have been performed to evaluate the extent of water
      circulation around IWA systems. In this study, 27 discrete monitoring points
      (MPs) were installed at a gasoline-contaminated site to assess the efficacy of
      IWA. Pressure transducers and dissolved oxygen (DO) probes were sealed into the
      MPs, allowing them to be used to characterize subsurface changes in total head
      and DO with depth, distance and orientation from a central injection well. No
      change in DO or in hydrocarbon total mass or distribution occurred across the
      site during two trials (41 and 20 days) of the system. Water level fluctuations
      during the trials were similar in all MPs, and were due to seasonal water table
      changes and rainfall events. No circulation cell was established around the IWA
      well after 41 days of operation, and the impact of the well extended less than
      90cm from it. Groundwater only circulated through the sand pack around the well.
      Little, if any, recharge occurred through the lower screen. Silt accumulated in
      the well, limiting its operation time, even with a fabric filter sock over the
      lower screen. Obviously, IWA was ineffective at this site, probably because the
      horizontal hydraulic conductivity (K(h)) of the soil opposite the lower screen
      was low (0.09cm per day) and because the distance between the two screens was
      short relative to the borehole radius. Long remediation times would likely make
      IWA unattractive at this or other sites where the K(h) of the soil is so low that
      the air injection rate would have to be low to prevent blowing the well dry.

PMID- 11230917
TI  - Validation of a polymerase chain reaction assay for monitoring the therapeutic
      efficacy of diminazene aceturate in trypanosome-infected sheep.
AB  - The diagnostic performance of a polymerase chain reaction assay (PCR) for
      monitoring the effectiveness of aceturate diminazene treatment was compared with
      those of an antibody-detection ELISA test and the buffy-coat technique using
      sheep experimentally infected with either savannah-type or forest-type
      Trypanosoma congolense or T. vivax. Within the period of infection, the PCR using
      specific savannah-type T. congolense primers showed a significant higher
      diagnostic sensitivity (p<0.05) than the buffy-coat technique. Both techniques
      gave closed results for detecting forest-type T. congolense or T. vivax
      infections. Following trypanocidal treatment, the PCR showed that specific
      product disappeared definitively 1 or 2 days later in animals in which a decrease
      of the antibody level and a significant improvement of the red packed cell volume
      were observed. The occurrence of relapse infection was detected by the PCR in one
      animal infected by T. vivax on day 19 post-treatment and confirmed by the
      persistence and increasing antibody level whereas the buffy-coat technique
      detected parasites 42 days later. Then, the PCR signals remained positive on
      several occasions while parasitaemia was detected only two times.The application
      of PCR combined with the antibody detection appeared to provide a useful tool as
      compared to the buffy-coat technique for monitoring the effectiveness of
      trypanocidal treatment.

PMID- 11230918
TI  - Demonstration of erythrophagocytosis in Trypanosoma congolense-infected goats.
AB  - Anaemia is the most prominent clinical sign of trypanosomosis in domestic animals
      but little is known about its pathogenesis. This work investigated
      erythrophagocytosis as the possible cause of anaemia. Pathogenic Trypanosoma
      congolense (IL3000) was intravenously inoculated into six goats at 3x10(6)
      trypanosomes per goat. Six other goats were maintained as controls. The infection
      was studied for 10 weeks and parasitaemia, packed cell volume (PCV) and serum
      protein levels were determined. The amount of erythrophagocytosis was determined
      from the amount of 51Cr-labelled red blood cells (RBCs) phagocytosed by self
      mononuclear cells (MNCs) in vitro and by microscopically counting phagocytosed
      RBCs on Giemsa stained smears of incubated mixtures of RBCs and self MNCs. The
      infection resulted in trypanosomosis with rapid progressive anaemia and mean
      peaks of parasitaemia of about 3x10(3)ml(-1). In infected goats, a significant
      (P<0.05) mean reduction in PCV (of 37-22%) was observed starting from about 20
      days up to 56 days post-infection. Within this same phase, significant (P<0.05)
      differences in mean radioactivity counts of (51)Cr incorporated into MNCs were
      observed with infected goats' samples having counts 50% higher than the control
      goats' samples. Microscopically, the mean number of phagocytosed RBCs in infected
      goats' MNCs was noted to be 80% higher (P<0.05) than that of control goats.
      Appreciable increases (P<0.05) in mean serum globulin levels, from 3.5 to
      4.7g/dl, were observed within 3 weeks of infection. The study showed that
      erythrophagocytosis is an important mechanism leading to anaemia in the
      pathophysiology of T. congolense infection in Zambian goats.

PMID- 11230919
TI  - Immunological and hematological response in experimental Toxocara canis-infected
      pigs.
AB  - The relationship between the immunological and hematological response to
      infection was studied in pigs inoculated experimentally with Toxocara canis. Two
      groups of four pigs were infected with doses of 1000 and 2000 infective eggs,
      respectively. Two uninfected animals were used as negative controls. Blood
      samples were collected from each pig once a week. Serological examination by
      ELISA to determine antibody levels against T. canis L2/L3 excretory-secretory
      (ES) antigens showed values higher than the positive cut-off point (1:32) for
      both the infected groups. These values increased from day 7 p.i. and remained
      high during the experimental period until day 56. Significant differences were
      recorded for the two inoculating doses (p</=0.01) from day 14 to 42 p.i. Western
      blots run on day 7 p.i. with serum from the 2000 eggs group showed two
      polypeptide bands of 70 and 55kDa. These same bands were observed for both
      infected groups from day 15 p.i. until the end of the experiment. Eosinophil
      counts were significantly higher (p</=0.05) for both inoculated groups between
      weeks 2 and 7 p.i. as compared with the control group. No significant changes
      were observed for other blood parameters. The pig is a useful animal model since
      T. canis induces an early immunological response and ELISA can detect the
      presence of these antibodies against T. canis L(2)/L(3) ES antigens in animals
      inoculated with low doses of Toxocara eggs.

PMID- 11230920
TI  - Occurrence of helminths in pig fattening units with different management systems
      in Northern Germany.
AB  - The helminth infections on 13 pig fattening farms with different management
      systems (complete or partial all-in-all-out system or continuous fattening) in
      North-Western Germany were investigated over at least three fattening periods.
      Pooled faecal samples were taken from pens once before and three times after
      anthelmintic treatment. At the beginning of fattening 34.9% of the samples
      contained helminth eggs, mainly from Oesophagostomum spp. (27.5%). Ascaris suum
      eggs were found in 10.5% of the samples, while other parasites were only rarely
      found. The number of pig-supplying farms was positively correlated with the
      helminth infection prevalence. Immediately after deworming, all pen samples were
      free of helminth eggs. However, the prevalences increased again, and by the end
      of fattening A. suum was found in 33.0% and strongylids in 6.0% of the samples.
      Pens harbouring A. suum-excreting pigs at the beginning of fattening had higher
      infection levels at the end, and this was also the case for nodular worms. The
      final prevalence of Ascaris was higher in partial exchange systems than in
      complete all-in-all-out systems and in old pig houses compared to new ones.
      Transmission of both Ascaris and Oesophagostomum was highest in autumn and
      winter. Thus, a single anthelmintic treatment at the beginning of fattening could
      not prevent infection during fattening, and the state of infection at the
      beginning was associated with the helminth burden at slaughter. Therefore, the
      purchase of parasite-free pigs in combination with appropriate hygiene management
      may minimise the initial infection pressure and keep subsequent infection of the
      herd at a minimum.

PMID- 11230921
TI  - Efficacy of doramectin injectable against Oestrus ovis and gastrointestinal
      nematodes in sheep in the southwestern region of France.
AB  - A study was conducted to evaluate the therapeutic efficacy of doramectin
      administered intramuscularly at a dose rate of 200 microg/kg to sheep harbouring
      naturally acquired infections of gastrointestinal nematodes and Oestrus ovis in
      the southwestern region of France. On day 0, 24 sheep were selected on the basis
      of positive faecal egg counts (>100 EPG) and positive assessment of O. ovis
      infection (including positive O. ovis antibody level and positive clinical
      score). The sheep were randomly allocated to a non-medicated control group (T1)
      or a doramectin-treated group (T2) of 12 animals each. On day 0, sheep in group
      T2 received a single intramuscular injection of doramectin (200 microg/kg),
      whereas those in group T1 received an intramuscular injection of saline solution
      (sodium chloride, 0.02ml/kg). Individual faecal egg counts were performed on days
      0, 1, 2, 3, 4, 5, 6, 7, and 14. Between days 14 and 16, all sheep were
      slaughtered, and worm and O. ovis burdens were determined. In doramectin-treated
      sheep, faecal egg counts had decreased to zero by day 4 for all recovered types
      of nematode eggs: strongyles, Nematodirus sp., Trichuris sp., and Rhabditidae sp.
      For strongyles, Nematodirus sp., and Rhabditidae, the percentage reductions in
      faecal egg counts (geometric means) of doramectin-treated sheep, compared to the
      non-medicated control sheep were 100% from days 4-7. For Trichuris sp., they were
      100, 99.7, 99.9, and 100% on days 4, 5, 6, and 7, respectively. On day 14,
      percentage reductions were 100% for Nematodirus sp. and Rhabditidae, and 99.8 and
      99.1% for strongyles and Trichuris sp., respectively. At necropsy, only adult
      nematodes and mainly first-stage O. ovis larvae were recovered. Doramectin was
      highly efficacious against the adult stages of Teladorsagia circumcincta (100%),
      Nematodirus battus (100%), Nematodirus filicollis (99.9%), Oesophagostomum
      venulosum (99.8%), and Trichuris sp. (99.3%). It was also 100% efficacious
      against first-stage larvae of O. ovis. No abnormal clinical signs or adverse
      reactions in any of the sheep treated with doramectin were observed.

PMID- 11230922
TI  - Comparative efficacy of several insecticides for control of cattle lice
      (Mallophaga: Trichodectidae and Anoplura: Haematopinidae).
AB  - Several insecticides were applied to cattle at various rates, mixtures,
      application methods and numbers of treatments and evaluated for control of cattle
      lice. The insecticides included permethrin at various rates as a pour-on with and
      without the synergist piperonyl butoxide (PBO), and also at various rates as a
      spray with and without PBO. Pirimiphos-methyl was evaluated as a pour-on at
      various rates and with one or two applications. Lambda cyhalothrin in
      microencapsulated formulation was compared to a non-microencapsulated
      formulation. Rabon(R) was applied as a pour-on at two rates and at one or two
      treatments for each rate. Dimilin(R) was applied as a pour-on at two rates and
      mixed with permethrin and applied at two rates. Five endectocides, Eprinex(R),
      Ivomec(R), Dectomax(R), Cydectin(R) and Phoenectin(R) were all applied at the
      same rate. The cattle utilized in this research were all infested with a mixture
      of lice species. The species included: Bovicola (Damalinia) bovis (L.),
      Haematopinus eurysternus (Nitzsch), Linognthus vituli (L.) and Solenoptes
      capillatus (Enderlein). Most of the cattle were infested with at least two
      species and some had three or all four species present. All of the treatments
      except permethrin 1.0%+5% PBO, at a rate of 3ml/45.4kgwt. provided acceptable
      lice control with one application. Data indicated that applying the insecticides
      in early January should provide enough control to render the need for a second
      treatment unnecessary.

PMID- 11230923
TI  - High prevalence of large spiny-tailed protostrongylid larvae in Iberian red deer.
AB  - The prevalence and abundance of protostrongylid larvae (Nematoda:
      Protostrongylidae) in 173 fecal samples of Iberian red deer (Cervus elaphus
      hispanicus Erxleben, 1777) are presented. Large (401(365-425)+/-24 micom) spiny
      tailed larvae, comparable to the descriptions of first stage Elaphostrongylus
      cervi larvae were found in 66.47+/-0.7% of the samples (range 6.8-100%, depending
      on the locality). The overall abundance of larvae in faces was overdispersed with
      an average of 24.94+/-96.23 (range 0-1202) larvae per gram, and ranged between
      sampling sites from 0.11+/-0.43 to 96+/-75 larvae per gram. This is the first
      report of large spiny-tailed protostrongylid larvae in deer from the western
      Mediterranean.

PMID- 11230924
TI  - Comparison of pulsed-field gel electrophoresis with random amplified polymorphic
      DNA for typing of Mycoplasma synoviae.
AB  - Pulsed-field gel electrophoresis (PFGE) analysis was developed and compared with
      random amplified polymorphic DNA (RAPD) method to type 18 Mycoplasma synoviae
      (MS) strains. All analysed strains were typeable by RAPD but only 89% of MS
      strains were typeable by PFGE because of DNA degradation. The discriminatory
      power of RAPD was greater than that of PFGE but the two techniques had a
      discriminatory index superior to 0.95, the threshold value for interpreting
      typing results with confidence. The in vitro, in ovo and in vivo reproducibility
      of both typing techniques was 100%. However, the interpretation of RAPD patterns
      was complicated because of inconsistent band intensity. Thus, these molecular
      typing techniques should be helpful for epidemiological studies of avian
      mycoplasma infections.

PMID- 11230925
TI  - Blocking enzyme-linked immunosorbent assay for detection of antibodies against
      Actinobacillus pleuropneumoniae serotype 6 in pig serum.
AB  - A blocking enzyme-linked immunosorbent assay (ELISA) detecting antibodies against
      Actinobacillus pleuropneumoniae (Ap) serotype 6 was developed. The blocking ELISA
      was based on the inhibition of a polyclonal antibody raised against Ap serotype
      6. Purified lipopolysaccharide from Ap serotype 6 was used as antigen. The
      blocking ELISA was tested against sera from pigs experimentally infected with the
      12 serotypes of Ap biotype 1. Cross-reaction with serotypes 3 and 8 but not with
      other serotypes was observed. The sensitivity and specificity of the test on a
      herd level were evaluated with sera from herds naturally infected with serotypes
      2, 6, 8 or 12 and with sera from herds free of infection with any Ap serotype.
      The blocking ELISA showed a high herd sensitivity (1.00 (0.79-1.00)) and
      specificity (0.97 (0.93-0.99)).

PMID- 11230926
TI  - Isolation of Actinobacillus pleuropneumoniae serotype 2 by immunomagnetic
      separation.
AB  - In Denmark porcine pleuropneumonia is most frequently caused by Actinobacillus
      pleuropneumoniae serotype 2 (60%). Isolation of A. pleuropneumoniae from nasal
      cavities or tonsils from carrier animals is complicated due to the mixed
      bacterial flora present. An immunomagnetic separation technique (IMS) using
      immunomagnetic beads (Dynabeads((R))) was developed for isolation of A.
      pleuropneumoniae serotype 2 from pure cultures and from heterogeneous
      suspensions. Different coating and washing procedures were evaluated in pure and
      mixed cultures using polyclonal (PAb) and monoclonal antibodies. The highest
      reisolation yield was achieved when the beads were coated with 1.5 microg PAb
      IgG/10(7) beads. After washing the beads for four times 9-24% of the bacteria
      could be reisolated depending on the amount of IgG attached to the beads and the
      number of beads used. The recovery was increased to 19-61% when only two washing
      steps were performed. The IMS was further evaluated using dilutions of A.
      pleuropneumoniae with added Pasteurella multocida (10(9) CFU/ml). After two
      washing steps 15% of the A. pleuropneumoniae cells and no P. multocida was
      reisolated. A detection limit of 10 CFU/ml was found in this heterogeneous
      suspension. No significant difference was observed when comparing the recovery of
      A. pleuropneumoniae from pure culture, from mixed cultures and from artificially
      inoculated tonsils. From 12 pigs inoculated with an aerosol of A.
      pleuropneumoniae serotype 2 the bacterium could not be detected from the nasal
      cavity or tonsils by cultivation or PCR 6 weeks later. By using IMS A.
      pleuropneumoniae serotype 2 could be reisolated from the tonsils of three pigs.
      The IMS method represents a valuable tool for isolation of A. pleuropneumoniae
      from tissue samples.

PMID- 11230927
TI  - Pilus ELISA and an anamnestic test for the diagnosis of virulent ovine footrot
      and its application in a disease control program in Nepal.
AB  - The immunological memory (anamnestic) responses in sheep recovered from virulent
      footrot (VFR) can be aroused by subcutaneous injection of outer membrane protein
      (OMP) antigens of Dichelobacter nodosus. The magnitude of this response is
      directly correlated to the highest antibody response attained during infection
      and memory lasts at least a year after recovery from VFR. However, some older
      animals show non-specific responses to OMP antigens. In this study an evaluation
      of D. nodosus pilus antigen for the anamnestic diagnosis of footrot in sheep was
      undertaken. The results indicated that the primary and anamnestic responses to
      pilus were similar in character to OMP antigen but were highly specific. The
      sensitivity of the procedure for detection of sheep with a history of VFR was
      approximately 80%. A low proportion of sheep with mild lesions due to virulent
      strains of D. nodosus reacted to anamnestic challenge. Anamnestic challenge with
      10 microg pilus was used in a VFR surveillance program in migratory sheep flocks
      in Nepal. Conventional diagnostic methods could not be applied during the disease
      transmission periods in these flocks because of their migration to alpine
      pastures far away from human habitation. The results supported clinical and
      bacteriological findings suggesting that virulent strains of D. nodosus have
      apparently been eliminated from these flocks in Nepal.

PMID- 11230928
TI  - Identification and detection of Actinobacillus pleuropneumoniae by PCR based on
      the gene apxIVA.
AB  - The apxIVA gene, a recently discovered RTX determinant of Actinobacillus
      pleuropneumoniae, was shown to be species-specific. DNA hybridization experiments
      using probes for various regions of apxIVA revealed that the 3'-terminus of this
      gene was present in all 14 serotypes of A. pleuropneumoniae but absent from
      phylogenetically related species. A primer pair spanning this region specifically
      amplified a 422bp fragment in PCR experiments with DNA from the reference strains
      of the 14 serotypes and 194 field strains isolated from various geographic
      locations worldwide. DNA sequence analysis of PCR products derived from all
      serotypes were identical except in serotypes 3, 8, and 10, which showed minor
      differences. The PCR did not amplify any product when DNA from 17 different
      bacterial species closely related to A. pleuropneumoniae was used as template. In
      addition, the PCR was negative with DNA of several Actinobacillus sp. which were
      initially characterized as A. pleuropneumoniae using routine phenotypic and
      serological analyses but which were subsequently shown by 16S rRNA sequence
      analysis to belong to yet undefined Actinobacillus species. The sensitivity of
      the PCR was determined to be 10pg of A. pleuropneumoniae DNA. A set of nested
      primers amplified a 377bp fragment specifically with A. pleuropneumoniae DNA. DNA
      titration experiments using the flanking and nested primer pairs showed an
      improved level of sensitivity to approximately 10fg of genomic DNA. The nested
      PCR was used to monitor the spread of A. pleuropneumoniae in pigs experimentally
      infected with a virulent serotype 1 strain and housed in a controlled environment
      facility. A. pleuropneumoniae DNA could be detected by nested PCR in nasal swab
      samples of infected pigs receiving either a high dose (5x10(5)) or a low dose
      (1x10(4)) challenge and in unchallenged cohorts that were contact-infected by the
      inoculated animals. Furthermore, PCR confirmed the presence of A.
      pleuropneumoniae in 16/17 homogenates from necrotic lung lesions, while the
      bacterium was successfully recovered from 13 of these lesions by culture.

PMID- 11230929
TI  - Rapid PCR detection of Salmonella in horse faecal samples.
AB  - A rapid polymerase chain reaction (PCR) assay was developed for detecting
      Salmonella in faeces of horses and assessed on samples from horses admitted to a
      veterinary hospital. Direct detection was achieved by amplification of part of
      ompC after extraction of DNA from faeces using a spin column method to reduce the
      amount of inhibitory substances in samples. An internal positive control was
      included to detect false negative results. While the sensitivity of the PCR assay
      was less than culture when assessed on faeces inoculated with Salmonella, its
      sensitivity on faecal samples obtained from horses was much greater than culture.
      Salmonella DNA was detected in 40% of faecal samples using the PCR assay while
      Salmonella were cultured from only 2% of the samples. The PCR assay has potential
      for use in either routine diagnosis or for detection of the carrier status in
      animals.

PMID- 11230930
TI  - Adaptation of Marek's disease virus to the Vero continuous cell line.
AB  - Marek's disease virus (MDV) is a highly infectious, cell-associated oncogenic
      herpesvirus. Production of MD vaccines has been limited to primary chicken and
      duck embryo fibroblast (CEF and DEF) cultures. These have a limited life span and
      cannot be readily stored in liquid nitrogen. Moreover, the need to prepare CEF
      and DEF cells on a regular basis from 10 to 11 day-old embryos derived from a
      flock that must be tested continuously for the presence of avian pathogens adds
      to the cost of vaccine production. A continuous cell line that would support MDV
      replication could have significant advantages for the rapid large-scale
      preparation of MD vaccines. In this report, we describe the adaptation to growth
      of CEF-grown preparations of serotype 1 and serotype 3 (herpesvirus of turkeys;
      HVT) strains of MDV in cells of the Vero continuous cell line. Although both
      viruses produced typical CPE, higher levels of infectious progeny and more
      extensive virus-specific immunofluorescence were obtained for HVT than for the
      serotype 1 virus. PCR and pulsed field electrophoresis (PFE) analysis of the DNA
      from Vero cells infected with either virus confirmed the presence of virus
      specific DNA.

PMID- 11230931
TI  - Experimental transmission of sheep-associated malignant catarrhal fever from
      sheep to Japanese deer (Cervus nippon) and cattle.
AB  - The assumption that sheep carry ovine herpesvirus-2 (OvHV-2), the causative agent
      of sheep-associated malignant catarrhal fever (SA-MCF), is widely accepted,
      albeit OvHV-2 has not been isolated. We attempted experimental contact
      transmission of MCF from Japanese sheep persistently infected with OvHV-2 to
      Japanese deer (Cervus nippon) and cattle. In Experiment 1, a deer was kept in
      close quarters with an infected ewe. In Experiment 2, a second deer was kept with
      the same ewe. In Experiment 3, two cows were each kept with two infected wethers.
      In Experiment 1, the deer developed clinical signs at 138 days after first
      contact and then died. OvHV-2 genes by polymerase chain reaction (PCR) and
      fluorescent antibodies to Alcelaphine herpesvirus-1 were detected in the affected
      deer. Moreover, sequences of PCR products (423bp), obtained by amplification of
      materials from the sheep and from the affected deer, coincided. These results
      clearly confirmed that the sheep was a carrier of OvHV-2, and that this virus had
      induced SA-MCF in a deer. In other experiments, no OvHV-2 infection occurred in
      deer and cattle during the 6-18 months periods of contact, though viral genes
      were detected in the nasal swabs and white blood cells of the sheep. To our
      knowledge, this is the first report on successful experimental transmission of
      MCF from OvHV-2-infected sheep to deer.

PMID- 11230932
TI  - Differential responses of Equus caballus and Equus asinus to infection with two
      pathogenic strains of equine infectious anemia virus.
AB  - Most in vivo studies with equine infectious anemia virus (EIAV) have been
      performed in horses and ponies (Equus caballus) with little published information
      available detailing the clinical responses of donkeys (Equus asinus) to infection
      with this virus. Consequently, donkeys were inoculated with two strains of EIAV
      (EIAV(PV) and EIAV(WY)) which have been documented to produce disease in E.
      caballus. Four ponies, 561, 562, 564 and 567 and two donkeys, 3 and 5 were
      infected with EIAV(PV) and one horse (94-10) and one donkey (4) were infected
      with EIAV(WY). Although the horse and ponies all experienced clinical signs of
      disease, which in some cases were severe, the donkeys remained asymptomatic
      throughout a 365-day observation period, except for mild transient reductions in
      platelet counts. The results from serological assays, virus isolation from plasma
      and detection of plasma-associated viral RNA by RT-PCR, indicated that initial
      replication of EIAV(PV) and EIAV(WY) was lower in donkeys than in horses and
      ponies. This conclusion was confirmed using competitive RT-PCR, in which viral
      RNA levels in the plasma of EIAV(PV)-infected ponies was up to 100,000-fold
      higher than in infected donkeys during the first 20 days post-infection (dpi).
      Similar results were obtained in the EIAV(WY)-infected animals, in which viral
      RNA burdens in the donkey at 20 dpi were 1000-fold less than in the horse.
      However, infection of donkey and horse monocyte-derived macrophage cultures with
      EIAV(PV) demonstrated that these cells in vitro were equally susceptible to virus
      induced cytopathic effects and yielded similar levels of progeny virus. This
      result suggests that factors other than host cell permissiveness mediate the
      clinical differences observed between horses and donkeys infected with EIAV(PV)
      or EIAV(WY).

PMID- 11230933
TI  - Design and validation of an ELISA for equine infectious anemia (EIA) diagnosis
      using synthetic peptides.
AB  - Three peptides derived from the equine infectious anemia virus (EIAV) surface
      proteins were synthesized to design and validate an ELISA for EIA diagnosis.
      Peptides identified as gp90-I and gp90-II correspond to the N- and C-terminal
      part of the surface glycoprotein gp90. Peptide gp45-1 overlaps the immunodominant
      epitope CIERTHVFC of the transmembrane glycoprotein gp45, and includes a
      hydrophilic chain close to the N-terminal end of this nonapeptide loop. Serum
      samples from 140 naturally infected horses with EIAV and a panel of 167 non
      immune equine sera obtained from non-infected animals were used. Differences in
      reactivity between positive and negative serum samples were clearly
      distinguished. Samples considered weak positive to the agar gel immunodiffusion
      (AGID) test were "true" positive in the ELISA. These results are consistent with
      the improved sensitivity of the ELISA in comparison with the AGID test. The
      cyclic peptide that mimics the immunodominant sequence of gp45 showed excellent
      reactivity, thus suggesting that its functional activity depends significantly on
      its conformation, since very low reactivity was observed in the linear form of
      the peptide. The detectability indices of positive and negative sera reached 98%
      when gp90-II and gp45-I synthetic peptides were used in the same assay,
      illustrating the high specificity and sensitivity of the assay. Our study
      represents a first approach for the design of a diagnostic kit, which would allow
      the rapid analysis of a large numbers of serum samples from horses, and could be
      applied in endemic areas with different prevalence of infection.

PMID- 11230934
TI  - Incidence of Mycobacterium paratuberculosis in raw sheep and goats' milk in
      England, Wales and Northern Ireland.
AB  - A blind survey of 104 raw sheep and goats' milk samples (90 goat, 14 sheeps) from
      bulk tanks on farms throughout England, Wales and Northern Ireland was carried
      out over a 5-month period (January-May 1998) in order to determine the incidence
      of Mycobacterium paratuberculosis. Each milk sample (100 ml) was divided into two
      50ml portions. One portion was decontaminated with 0.75% hexadecylpyridinium
      chloride for 5h before culture on slopes of Herrold's egg yolk medium and in
      BACTEC radiometric medium. The second portion was subjected to immunomagnetic
      separation followed by IS900 PCR (IMS-PCR). The IMS-PCR assay was employed in
      order to provide a more rapid indication of the presence of M. paratuberculosis
      in each milk sample than is possible by culture. Information on the Johne's
      disease status of the sheep and goat herds that took part in the survey was not
      sought at the time of milk sampling. However, it subsequently emerged that at
      least some of the herds whose bulk milk was tested during this study were
      previously or currently infected with Johne's disease. Overall, during this
      survey one raw goats' milk sample tested positive for the presence of M.
      paratuberculosis by IMS-PCR (<1% of milk samples tested) but no viable M.
      paratuberculosis were isolated by culture. The results of this study suggest that
      bulk raw sheep and goats' milk from these regions of the UK may not represent
      significant vehicles of transmission of M. paratuberculosis to humans.

PMID- 11230935
TI  - Bacillus subtilis spores competitively exclude Escherichia coli O78:K80 in
      poultry.
AB  - Newly hatched specific pathogen-free chicks were dosed with a suspension of
      Bacillus subtilis spores prior to challenge with Escherichia coli O78:K80, a
      known virulent strain associated with avian colibacillosis, 24h later. A single
      oral inoculum of 2.5x10(8) spores was sufficient to suppress all aspects of E.
      coli O78:K80 infection. Colonisation of deep organs was reduced by a factor of
      over 2log(10) whilst colonisation of the intestine, as measured by direct caecal
      count, was reduced over 3log(10). Shedding of E. coli O78:K80 was measured by
      semi-quantitative cloacal swabbing and was reduced significantly for the duration
      of the experiment, 35 days. B. subtilis persisted in the intestine although with
      decreasing numbers over the same period. Challenge with the same dose 5 days
      after pre-dosing with spores overcame any suppressive effect of the spores.

PMID- 11230936
TI  - Serogroups and antimicrobial susceptibility among Escherichia coli isolated from
      farmed mink (Mustela vison Schreiber) in Denmark.
AB  - Escherichia coli is commonly found in outbreaks of diarrhoea in mink during the
      production season although its role as a primary causal organism remains unclear.
      The present study was undertaken to determine the serogroups and antimicrobial
      susceptibility of E. coli isolates from healthy and diarrhoeic mink. Rectal swabs
      were taken from healthy and diseased animals, on six different farms, once at the
      onset of disease and again approximately 2 weeks later. The swabs were subjected
      to bacteriological investigation; a total of 210 E. coli were isolated, 98 from
      healthy animals and 112 from diseased. All isolates were serotyped and MICs were
      determined for nine antimicrobial compounds. Non-haemolytic isolates numbered
      147, whereas 63 were haemolytic. Both haemolytic and non-haemolytic isolates were
      isolated from both healthy and diseased animals.A wide range of serogroups was
      detected, the most frequent being O2 (11.0%), O78 (11.0%), O153 (7.1%), O25
      (5.7%), O6 (4.8%), and O15 (4.8%), but diarrhoea was not associated with specific
      serogroups. All isolates were sensitive to enrofloxacin, neomycin, gentamicin and
      colistin. In contrast, considerable variations in susceptibility were found among
      the six mink farms, for tetracycline (0-46.4%, average 21.9), ampicillin (2.9
      50.0%, average 23.3), spectinomycin (8.0-35.7%, average 21.9), sulfamethoxazole
      (8.6-57.7%, average 30.0) and trimethoprim (0-35.7%, average 9.5). Resistance to
      tetracycline was statistically more prevalent among haemolytic than among non
      haemolytic strains.In conclusion, serogrouping and haemolysin testing failed to
      identify any association with diarrhoeal disease and antimicrobial resistance was
      highly variable between different mink farms.

PMID- 11230937
TI  - Molecular epidemiology and genetic linkage of macrolide and aminoglycoside
      resistance in Staphylococcus intermedius of canine origin.
AB  - A collection of 77 Staphylococcus intermedius isolates from dogs and cats in
      Switzerland was examined for resistance to erythromycin. Resistance profiles for
      14 additional antibiotics were compared between erythromycin-resistant and
      susceptible isolates. A resistance prevalence of 27% for erythromycin was
      observed in the population under study. Complete correlation between resistance
      to erythromycin, and to spiramycin, streptomycin, and neomycin was observed. The
      erythromycin-resistant isolates all had a reduced susceptibility to clindamycin
      when compared to the erythromycin-susceptible isolates. Both constitutive and
      inducible resistance phenotypes were observed for clindamycin. Ribotyping showed
      that macrolide-aminoglycoside resistance was randomly distributed among unrelated
      strains. This suggests that this particular resistance profile is not related to
      a single bacterial clone but to the horizontal transfer of resistance gene
      clusters in S. intermedius populations. The erythromycin-resistant isolates were
      all carrying erm(B), but not erm(A), erm(C), or msr(A). The erm(B) gene was
      physically linked to Tn5405-like elements known as resistance determinants for
      streptomycin, streptothricin, neomycin and kanamycin. Analysis of the region
      flanking erm(B) showed the presence of two different groups of erm(B)-Tn5405-like
      elements in the S. intermedius population examined and of elements found in Gram
      positive species other than staphylococci. This strongly suggests that erm(B) or
      the whole erm(B)-Tn5405-like elements in S. intermedius originate from other
      bacterial species, possibly from enterococci.

PMID- 11230938
TI  - Effects of an experimental infection with Actinobacillus pleuropneumoniae on the
      interferon-alpha and interleukin-6 producing capacity of porcine peripheral blood
      mononuclear cells stimulated with bacteria, virus or plasmid DNA.
AB  - The effect of a bacterial infection on interferon-alpha (IFN-alpha) and
      interleukin-6 (IL-6) production by porcine cells was studied in specific pathogen
      free (SPF) pigs, infected intranasally with Actinobacillus pleuropneumoniae
      serotype 2. Three experimental groups of five pigs were used: infected non
      treated pigs, infected pigs that were treated with enrofloxacin at disease onset,
      and non-infected, non-treated control pigs. Blood samples were collected from all
      pigs on the day of infection and on days 1, 4, 7, 13 and 17 post-infection. Sera
      were analysed for presence of antibodies to A. pleuropneumoniae and for the
      cytokines IL-6 and IFN-alpha. Ability to produce these cytokines was tested in
      vitro using whole blood cultures stimulated with inactivated virus (Aujeszky's
      disease virus infected porcine kidney cells (ADV/PK-15)), inactivated bacteria
      (A. pleuropneumoniae) or bacterial plasmid (pcDNA3). All cytokine inducers were
      used neat or pre-incubated with the transfectious agent lipofectin. IL-6 appeared
      in the serum of all infected non-treated animals but no IFN-alpha was found in
      the serum of any of the experimental pigs. Accordingly, the bacteria induced a
      substantial IL-6 but hardly any IFN-alpha production when tested in vitro.
      However, following incubation with lipofectin, the inactivated bacteria as well
      as pcDNA3 became efficient inducers of IFN-alpha in whole blood cultures. The
      increased IFN-alpha production, previously recorded in vitro during the acute
      phase of infection with A. pleuropneumoniae, was confirmed using lipofected
      plasmid DNA and it was indicated that leukocytes obtained from infected but
      apparently cured animals also exhibited an increased production of IFN-alpha.
      Thus, even mild/sub-clinical bacterial infections may affect cytokine production
      in pigs.

PMID- 11230939
TI  - Evaluation of the components of a commercial probiotic in gnotobiotic mice
      experimentally challenged with Salmonella enterica subsp. enterica ser.
      Typhimurium.
AB  - Vitacanis((R)), a probiotic preparation containing a Lactobacillus acidophilus,
      an Enterococcus faecium and a Saccharomyces cerevisiae, has been developed for
      the prevention of intestinal disorders in dogs and cats. In the present study,
      these microorganisms were tested jointly or singly during experimental infection
      of gnotobiotic mice with Salmonella Typhimurium. Four experimental groups
      consisting of animals given probiotics jointly or singly and a control group
      consisting of germfree mice were used. The groups were treated with one or three
      of the microorganisms (experimental) or PBS (control) 10 days before intragastric
      challenge with a suspension containing about 10(2) cells of the bacterial
      pathogen. A higher survival (P<0.05) was observed in gnotobiotic mice given E.
      faecium (82%). All the animals in the other groups died after the challenge but
      the survival time was longer (P<0.05) for groups given all three of the
      microorganisms (7.4+/-2.4 days) or given only L. acidophilus (7.2+/-2.9 days)
      than for the control mice (4.4+/-1.1 days) and the mice that received S.
      cerevisiae (4.9+/-1.6 days) mice. The survival data agreed with the
      histopathological findings which showed more severe liver and intestinal lesions
      in control mice and in mice given Saccharomyces. In vitro antagonistic assays
      showed inhibition growth of E. faecium and S. Typhimurium around the colonies of
      L. acidophilus and for S. Typhimurium around the colonies of E. faecium. However,
      in vivo, S. Typhimurium became similarly established in the digestive tract of
      gnotobiotic mice at levels ranging from 10(8) to 10(10)CFU/g of feces and
      remained at these high levels until the animals died or were sacrificed. Among
      the three probiotic components of the commercial product Vitacanis((R)), E.
      faecium was the only one that provided protection against challenge with S.
      Typhimurium. Protection was not due to the reduction of the intestinal
      populations of the pathogenic bacteria.

PMID- 11230940
TI  - Global forensic anthropology in the 21st century.
AB  - While it has a long history, the last 30 years have brought considerable advances
      to the discipline of forensic anthropology worldwide. Every so often it is
      essential that these advances are noticed and trends assessed. It is also
      important to identify those research areas that are needed for the forthcoming
      years. The purpose of this special issue is to examine some of the examples of
      research that might identify the trends in the 21st century. Of the 14 papers 5
      dealt with facial features and identification such as facial profile
      determination and skull-photo superimposition. Age (fetus and cranial thickness),
      sex (supranasal region, arm and leg bones) and stature (from the arm bones)
      estimation were represented by five articles. Others discussed the estimation of
      time since death, skull color and diabetes, and a case study dealing with a mummy
      and skeletal analysis in comparison with DNA identification. These papers show
      that age, sex, and stature are still important issues of the discipline. Research
      on the human face is moving from hit and miss case studies to a more
      scientifically sound direction. A lack of studies on trauma and taphonomy is very
      clear. Anthropologists with other scientists can develop research areas to make
      the identification process more reliable. Research should include the assessment
      of animal attacks on human remains, factors affecting decomposition rates, and
      aging of the human face. Lastly anthropologists should be involved in the
      education of forensic pathologists about osteological techniques and
      investigators regarding archaeology of crime scenes.

PMID- 11230941
TI  - The roughness of the supranasal region--a morphological sex trait.
AB  - The supranasal region often attracts attention by a remarkable rough and jagged
      quality of the bony surface caused by an irregular supranasal suture and
      additional holes and pores. Some authors point out that there is a positive
      relation between the supranasal suture, the superciliar arches, and the forehead
      contour. For this a relation to sex is conceivable. This present study was done
      to prove the value of this morphological trait for sexing skulls.A total of 80
      human skulls of known sex (40 females, 40 males) were collected from autopsy
      material used in anatomy teaching classes and from forensic cases. The mean age
      of the female sample was 70.98 years (minimum 38, maximum 93), that of the male
      sample was 74.10 years (minimum 57, maximum 99). To quantify the roughness of the
      supranasal region the calculation of the box-counting dimension was used. The
      results were normally distributed in both, the male and female group. The male
      dimension values were well grouped (maximum 1.51111, minimum 0.98765, mean
      1.26159, S.D. 0.12268, 95% CI 1.22236-1.26604) whereas the female showed a wide
      range (maximum 1.46744, minimum 0.44755, mean 1.15052, S.D. 0.21388, 95% CI
      1.08212-1.21892), widely overlapping the male range. Statistical analysis showed
      that there was a less than 1% probability that the female box-counting dimension
      was lower than the male by chance (P-value 0.00593). For this results the
      admission of the trait 'quality of the supranasal region' into a catalogue of
      features regarding morphognostic sex determination following the scheme:
      hyperfemininity: very smooth and regular--femininity: more smooth and regular-
      indifferent--masculinity: more rough and irregular--hypermasculinity: very rough
      and irregular, seems to be justified.

PMID- 11230942
TI  - Sex determination from the head of the femur of South African whites and blacks.
AB  - The current practice whereby criminals dismember the remains of their victims in
      an attempt to make their identification difficult requires that simple methods of
      sex determination from fragmented skeletal remains are available to forensic
      anthropologists and skeletal biologists. The head of the femur is an example of
      such bone fragments. Identification and demarking points have been derived from
      the diameters of the head of the femur and used to determine the sex of
      individuals. It has been shown, however, that the numerical values of these
      parameters that permit sex identification vary between races. The objectives of
      the present study were therefore to establish the standard numerical values of
      the identification and demarking points for sex determination in South African
      whites and blacks and to see if these standards are different in the two races. A
      total of 520 femurs of white (160 males and 100 females) and black (160 males and
      100 females) South Africans were obtained from the Raymond Dart Skeletal
      Collection in the Department of Anatomical Sciences of the University of the
      Witwatersrand, Johannesburg, South Africa. The vertical and transverse diameters
      of the heads of the femurs were measured by means of a stainless steel vernier
      caliper. Identification and demarking points were derived from the values of
      these diameters. The head diameter identification point and demarking point were
      found to be sexually dimorphic in both white and black South Africans. The mean
      head diameter of the male femur was significantly greater than the mean head
      diameter of the female femur in both population groups (significant at P<0.001).
      These values were correspondingly greater in the white than the black population.
      The numerical values of the male identification and demarking points were higher
      than the corresponding female values in the two population. In both sexes, these
      values were greater in the whites than the blacks South Africans. It is concluded
      that the diameters of the head of the femur and the identification and demarking
      points that are derived from them are sexually dimorphic in South African white
      and black populations. However, the numerical values of these sex-determining
      bone parameters defer between the two population groups. Therefore, it is
      necessary to determine race-specific standards of these parameters.

PMID- 11230943
TI  - Sex determination and estimation of stature from the long bones of the arm.
AB  - The determination of sex and the estimation of stature from bones play an
      important role in identifying unknown bodies, parts of bodies or skeletal
      remains. In medico-legal practice statements on the probable sex of a decomposed
      body or part of a body are often expected even during autopsy. The present study
      was, therefore, restricted to few easily accessible dimensions from bones which
      were prepared only by mechanically removing soft tissues, tendons and ligaments.
      The specimens came from the Anatomical Institutes in Munich and Cologne from the
      years 1994-1998 including a total of 143 individuals (64 males and 79 females).
      The mean age was 79 years (46-108), the mean body height 161cm (134-189). The
      following measurements were taken: maximum humeral length (mean: 33.4cm in males;
      30.7cm in females), vertical humeral head diameter (mean: 5.0cm in males, 4.4cm
      in females), humeral epicondylar width (mean: 6.6cm in males; 5.8cm in females),
      maximum ulnar length (mean: 26.5cm in males, 23.8cm in females), proximal ulnar
      width (mean: 3.4cm in males, 2.9cm in females), distal ulnar width (mean: 2.2cm
      in males; 1.8cm in females), maximum radial length (mean: 24.6cm in males; 22.0cm
      in females), radial head diameter (mean: 2.6cm in males, 2.2cm in females) and
      distal radial width (mean: 3.6cm in males; 3.2cm in females). The differences
      between the means in males and females were significant (P<0.0005). A
      discriminant analysis was carried out with good results. A percentage of 94.93%
      of cases were correctly classified when all measures of the radius were applied
      jointly, followed by humerus (93.15%) and ulna (90.58%). Applied singly, the
      humeral head diameter allowed the best distinction (90.41% correctly grouped
      cases), followed by the radial length (89.13%), the radial head diameter (88.57%)
      and the humeral epicondylar width (88.49%). The linear regression analysis for
      quantifying the correlation between the bone lengths and the stature led to
      unsatifactory results with large 95%-confidence intervals for the coefficients
      and high standard errors of estimate.

PMID- 11230944
TI  - Estimation of fetal age from dimensions of atlas and axis ossification centers.
AB  - The atlas and axis ossification centers of 106 human fetal and neonate skeletons
      were measured. The skeletons belong to the collection in the Department of
      Forensic Medicine of the Albert Szent-Gyorgyi Medical University, Szeged,
      Hungary. The age of the skeletons ranged from 4 to 10 lunar months. Nine linear
      measurements on the atlas, seven on the axis neural arches ossification centers
      and three on each one of the axis centra ossification centers were taken. We did
      simple and multiple linear regression analysis to estimate the age of fetuses.
      The results show that it is possible to use regression equations to estimate the
      fetal body length and age from atlas and axis ossification centers measurements
      during the whole period of development studied. The study of size and shape of
      the ossification centers using factorial analysis (principal component analysis)
      shows that the shape of the dens of the axis might be useful to estimate fetal
      viability.

PMID- 11230946
TI  - The colour of the human skull.
AB  - The colour of the human skull was determined from 124 fresh skull samples using
      the tristimulus colour measurement system "Micro Color" and listed as The
      Commission Internationale de l'Eclairage (CIE) L*a*b*-values. The skulls were
      found to be relatively light (L*=72.5), nearly colourless on the a*-axis (a*=
      7.4), and slightly yellow (b*=16.4). No difference was found between the colours
      of the outer and the inner surfaces of the skulls. Including a small number (n=8)
      of skulls from diabetic patients in the study, we detected no colour difference
      between the samples from diabetics and non-diabetics. However, a hitherto unknown
      correlation between the subjects' age and the yellowness (b*-value) of the skull
      could be demonstrated.

PMID- 11230945
TI  - Cranial thickness in relation to age, sex and general body build in a Danish
      forensic sample.
AB  - The cranial thickness was measured in 64 individuals (43 males, 21 females)
      autopsied at our institute. The thickness was measured by taking a biopsy with a
      trephine at four specific locations on the skull. Complete medical records and
      pathologic autopsy results were available. While none of the individuals had
      suffered from diseases affecting bone or bone metabolism as such, a large sub
      group consisted of individuals with a history of, and autopsy finds consistent
      with, chronic substance and alcohol abuse. There was no statistically significant
      difference in cranial thickness measures between this group and the rest of the
      material. Subsequent analyses failed to reveal any correlations between the
      cranial thickness and sex and age and height and weight of the individual. This
      is in accordance with most earlier studies, which likewise show no correlation,
      or only very faint trends, between cranial thickness and these parameters. This
      study, thus, adds to other studies showing that cranial thickness cannot be used
      in aging or sexing human remains. Likewise, in a forensic pathological setting,
      cranial thickness cannot be inferred from the individuals stature and build,
      which may be an issue in cases of interpersonal violence with cranial trauma.

PMID- 11230947
TI  - An Indian mummy: a case report.
AB  - A case of mummification occurring in northwest India (Chandigarh) is described. A
      middle-aged man developed an abscess on his back and was treated by a mystical
      man who did not allow him any food or water. After a few days the patient died.
      On the advice of the mystical man the body was kept in a room which was made hot
      and dry. The police discovered the body after 2 years. A postmortem examination
      was conducted and findings are reported.

PMID- 11230948
TI  - The reliability of forensic osteology--a case in point. Case study.
AB  - The medico-legal investigation of skeletons is a trans-disciplinary effort by
      forensic scientists as well as physical anthropologists. The advent of DNA
      extraction and amplification from bones and teeth has led to the assumption that
      morphological assessment of skeletal remains might soon become obsolete. But
      despite the introduction and success of molecular biology, the analysis of
      skeletal biology will remain an integral part of the identification process. This
      is due to the fact, that the skeletal record allows relatively fast and accurate
      inferences about the identity of the victim. Moreover, a standard biological
      profile may be established to effectively narrow the police investigator's search
      parameters. The following study demonstrates how skeletal biology may collaborate
      in the forensic investigation and support DNA fingerprinting evidence. In this
      case, the information gained from standard morphological methods about the
      unknown person's sex, age and heritage immediately led the police to suspect,
      that the remains were that of a young man from Vietnam, who had been missing for
      2.5 years. The investigation then quickly shifted to prove the victim's identity
      via DNA extraction and mtDNA sequence analysis and biostatistical calculations
      involving questions of kinship [4].

PMID- 11230949
TI  - An estimation of the post-mortem interval in human skeletal remains: a
      radionuclide and trace element approach.
AB  - Estimation of the post-mortem interval remains a contentious issue, with forensic
      pathologists often relying upon the recognition of morphological changes.A
      radionuclide approach has often been suggested in the literature, although
      limitations have prevented its application, most notably those of diagenesis.
      Within this pilot study, we show for the first time that there is a correlation
      between certain radionuclide content and time since death.A larger study is
      proposed to confirm these findings and possibly provide a calibration against
      which bones uncovered can be dated.

PMID- 11230950
TI  - Identification of unknown dead bodies by X-ray image comparison of the skull
      using the X-ray simulation program FoXSIS.
AB  - The aim of the study was to improve the objectivity of X-ray image comparison for
      the identification of unknown dead individuals. CT-data were collected for 30
      macerated skulls. An already presented computer program which uses CT data to
      establish virtual X-ray images was used to obtain X-rays with different beam
      angulations simulating rotation, dorsal flexion, and ventral flexion. Specific
      parameters were measured on the simulated images. The frontal sinus reveals the
      highest variability not only between the individual skulls but also within an
      individual skull in different positions. The most consistent parameters with
      respect to different positions were the skull breadth, the biorbital breadth and
      the bizygomatic breadth. In a blind study, three out of 24 skulls could clearly
      be identified just by measured distances although the positions were different
      and unknown to the investigator. The dimensions of the frontal sinus do not
      correlate with the other skull parameters (analysis of covariance). Based on the
      presented results, we propose a method that will calculate the probability of
      identity. The presented results demonstrate that the comparison of X-ray images
      can be undertaken in an objective way by quantifying the probability of identity
      even when the comparative images were made under different conditions.

PMID- 11230952
TI  - An economised craniofacial identification system.
AB  - It has been attempted to develop an economised craniofacial identification
      system, as a special automated version of photo/video superimposition technique,
      that can deal with common cases of personal identification with the aid of a
      skull and a nearly front view face photograph of the suspected victim. The
      proposed method is economic in respect of (i) cost of hardware configuration,
      (ii) processing time as well as (iii) manual labour involved. Over and above, it
      has got a capability to take care of ambiguities due to soft tissue thickness
      during the selection of facial features, which is a part of the procedure. In
      order to reconstruct a 2-D cranial image, superimposable over the facial one, the
      new method does not need any reconstruction of a digitised 3-D cranial image. It
      works simply by a suitable segment-wise processing of a 2-D cranial image with
      the aid of the symmetry perceiving adaptive neuronet (SPAN), that has recently
      been introduced in connection with nearly front view facial image recognition.
      The final comparison of the facial and the superimposable cranial images is as
      versatile as the same for facial image recognition by SPAN.A practical
      application of this extended version of SPAN has been demonstrated in the present
      paper.

PMID- 11230951
TI  - Ultrasonic assessment of facial soft tissue thicknesses in adult Egyptians.
AB  - The production of a three-dimensional plastic face on an unknown human skull has
      been practiced sporadically since the latter part of the last century. In recent
      years, the technique has been revived and applied to forensic science cases. The
      morphometric method of forensic facial reconstruction rests heavily on the use of
      facial soft tissue depth measurements. Moreover, it has been established that
      measurements made on the living are of more value than those made on the dead. In
      view of the well-known genetic complexities of the Egyptians, and the lack of
      knowledge of average facial soft tissue depths of the Egyptians that makes facial
      reconstruction questionable, it was decided to set up a table of norms for facial
      tissue thicknesses in 204 adult Egyptians aged 20-35 years. Tissue depths at 17
      established landmarks (according to Aulsebrook et al. [Forensic Sci. Int. 79
      (1996) 83]) were obtained using ultrasonic probing. The study revealed a unique
      spectrum of measurements for the Egyptians that might be useful for facial
      reconstruction purposes with obvious sexual dimorphism in facial soft tissue
      thickness. Additionally, the study provided evidence for the presence of
      interpopulation differences in average facial soft tissue thicknesses as
      evidenced from the comparison of the present data of Egyptians with those
      previously reported for some other populations.

PMID- 11230953
TI  - Cranio-facial morphanalysis: a new method for enhancing reliability while
      identifying skulls by photo superimposition.
AB  - Skull-photograph superimposition continues to be the most prevalent method
      employed for identifying a skull recovered in a criminal case as that belonging
      to a putative victim whose face photograph is available. The reliability of
      identification achieved has been shown to be 91%, indicating the possibility of a
      skull mismatching with a face photograph belonging to a person other than the
      actual deceased. This lack of reliability dampens the confidence of the expert
      and in turn confounds the mind of the judge. It has been shown that the
      variations in the shape of the facial organs are influenced by the corresponding
      variations in the skeletal elements of the facial skull. "Cranio-facial
      morphanalysis", a new anthroposcopic method proposed here for evaluating the
      shape correlations between a skull and a face photograph, when applied conjointly
      with skull-photograph superimposition is shown to increase the reliability in
      forensic skull identification.

PMID- 11230954
TI  - Craniometry and mathematical calculations as a method for viscero-cranium profile
      determination.
AB  - The aim of this work is to prove the application of craniometry in determining
      the identity of unknown bodies. There is a great correlation between the viscero
      cranium appearance and the osseous structure, the said correlation following
      mathematical rules and thus being possible to be calculated. Various segments of
      the skull and different size of the angles they make with each other are directly
      responsible for the graphic profile of viscero-cranium. The nasal bones and their
      angle are the basis to determine the shape and size of the nose.

PMID- 11230955
TI  - Development and application of ovine reproductive technologies: an Indian
      experience.
AB  - Sheep play an important role in the Indian economy by providing employment to a
      large population of marginal and landless farmers. The production from native
      breeds is relatively low due to their poor reproductive efficiency. Embryo
      transfer technology can be utilised for faster multiplication of elite animal to
      increase the genetic gain. A great deal of research is involved to overcome the
      constraints in the technology, i.e. expensive and complicated nature of the
      technology and low success rate. In order to avoid surgical involvement,
      procedures of laparoscope aided embryo collection and transfer have been
      developed. Although the use of FSH of ovine origin has given more consistent
      superovulatory response, but it is still too low to get sufficient numbers of
      progeny from a donor ewe. The progress made in cryopreservation of ram semen has
      opened the possibility for conservation and utilisation of frozen semen of elite
      rams in sheep improvement programme. The lambing rate obtained after laparoscope
      aided intrauterine artificial insemination with frozen semen is encouraging but
      the impetus is now to develop the non-invasive transcervical insemination
      technique.

PMID- 11230956
TI  - Genetic modelling of test day records in dairy sheep using orthogonal Legendre
      polynomials.
AB  - Test day milk yields of three lactations in Sfakia sheep were analyzed fitting a
      random regression (RR) model, regressing on orthogonal polynomials of the stage
      of the lactation period, i.e. days in milk. Univariate (UV) and multivariate (MV)
      analyses were also performed for four stages of the lactation period, represented
      by average days in milk, i.e. 15, 45, 70 and 105 days, to compare estimates
      obtained from RR models with estimates from UV and MV analyses. The total number
      of test day records were 790, 1314 and 1041 obtained from 214, 342 and 303 ewes
      in the first, second and third lactation, respectively. Error variances and
      covariances between regression coefficients were estimated by restricted maximum
      likelihood. Models were compared using likelihood ratio tests (LRTs). Log
      likelihoods were not significantly reduced when the rank of the orthogonal
      Legendre polynomials (LPs) of lactation stage was reduced from 4 to 2 and
      homogenous variances for lactation stages within lactations were considered. Mean
      weighted heritability estimates with RR models were 0.19, 0.09 and 0.08 for
      first, second and third lactation, respectively. The respective estimates
      obtained from UV analyses were 0.14, 0.12 and 0.08, respectively. Mean permanent
      environmental variance, as a proportion of the total, was high at all stages and
      lactations ranging from 0.54 to 0.71. Within lactations, genetic and permanent
      environmental correlations between lactation stages were in the range from 0.36
      to 0.99 and 0.76 to 0.99, respectively. Genetic parameters for additive genetic
      and permanent environmental effects obtained from RR models were different from
      those obtained from UV and MV analyses.

PMID- 11230957
TI  - Estimates of genetic parameters for direct and maternal effects on birth weight
      of local sheep in United Arab Emirates.
AB  - Genetic parameters for birth weight were estimated for two sets of purebred and
      crossbred lambs in United Arab Emirates, using animal model methods. Data were
      analyzed by restricted maximum likelihood (REML). Five different animal models
      were fitted. Model 1 considered the animal as the only random effect. Models 2
      and 3 included in addition to the additive direct effect of the animal, the
      additive maternal and the permanent maternal environmental effects, respectively.
      Model 4 fitted both the additive maternal and permanent environmental effects.
      Model 5 was the same as model 4, except that a covariance between the direct and
      the maternal additive effects was included. Estimates of direct heritability were
      substantially higher when maternal effects were ignored. Introducing the additive
      maternal effect to model 2 reduced the estimate of additive heritability by 28
      and 14% of sigma;(p)(2) for the purebred and crossbred lambs, respectively.
      Estimates of additive direct and additive maternal heritabilities with model 4
      were 0.10 and 0.33, and 0.45 and 0.10 for purebred and crossbred lambs,
      respectively. The correlation between direct and maternal genetic effects for the
      combined (purebred+crossbred lambs) data set was large and negative. These
      results indicate that in addition to additive direct effect, additive maternal
      effect for birth weight was important.

PMID- 11230958
TI  - Morphological changes in the gonads of the Sabi ram experimentally infected with
      Trypanosoma congolense.
AB  - Indigenous Sabi rams of Southern Africa were experimentally infected with
      Trypanosoma congolense for 8 and 16 weeks. Testes weights (g) were significantly
      (P<0.05) lower in the infected (249.7+/-26.4) compared to the control (372.63+/
      19.4) animals. Histopathological and ultrastructural changes included
      seminiferous tubular atrophy and mononuclear infiltration in the testis, and
      lesions in the epithelium of the corpus epididymidis (middle segment) as well as
      spermatozoa in the cauda epididymidis. The gonadal lesions may have the
      capability to impair fertility in Sabi rams infected with Trypanosoma congolense.

PMID- 11230959
TI  - Effects of dietary tallow level on performance of Alpine does in early lactation.
AB  - Sixty Alpine does (initial BW 47+/-1.3kg) were used to determine effects of
      dietary inclusion of different levels of partially hydrogenated tallow on
      performance in early lactation (weeks 3-11). Treatments entailed a 30%
      concentrate, negative control (NC) diet and five diets higher in concentrate (42
      46%) with 0, 1.5, 3.0, 4.5 or 6.0% DM of partially hydrogenated tallow (0T, 1.5T,
      3.0T, 4.5T and 6.0T, respectively). DM intake was 1.54kg per day for the NC and
      1.86, 1.80, 1.99, 2.17 and 1.96kg per day for the five tallow treatments,
      respectively, BW was similar among treatments and increased as the trial
      progressed (47.4, 48.4, 49.8, 50.4, 50.8 and 51.3kg at weeks 3, 5, 7, 9, 11 and
      13, respectively). Milk yield was lower (P<0.05) for NC (2.61kg per day) compared
      with the mean of the other diets and changed quadratically (P<0.05) as tallow
      level increased (2.85, 3.08, 3.14, 3.21 and 2.69kg per day for the five tallow
      treatments, respectively). Milk fat concentration was lower (P<0.05) for NC
      (2.94%) than for the mean of other diets and increased linearly (P<0.05) with
      increasing tallow level (3.00, 3.17, 3.34, 3.48 and 3.58%) whereas, milk protein
      concentration was not affected by level of tallow (2.72, 2.80, 2.93, 2.85, 2.90
      and 2.90% for NC, and the five tallow treatments, respectively). The estimated
      NE(l):4% fat-corrected milk yield ratio was 0.93Mcal/kg for NC and 1.30, 1.11,
      1.21, 1.37 and 1.44Mcal/kg for the five tallow treatments, respectively. The
      results indicated that in Alpine does, milk yield in early lactation increased as
      dietary tallow level was increased to 3 and 4.5% but decreased when the level was
      increased to 6%, although milk fat concentration increased linearly and the
      protein level was unchanged. These results suggest beneficial usage by lactating
      Alpine does of low to moderate levels of partially hydrogenated tallow in diets
      moderate in concentrate level, although ingredient availability and costs will
      influence ultimate dietary ingredient decisions.

PMID- 11230960
TI  - The effect of dietary crude protein level on intake, growth, protein retention
      and utilization of growing male Saanen kids.
AB  - The effects of increasing dietary levels of crude protein on growth, feed intake,
      feed efficiency and composition of gain in male Saanen kids were studied. Four
      groups of four kids each initially weighing 12.1+/-0.18kg and having a weight
      gain of 195+/-16g/d were penned individually and fed for 73 to 124 days up to
      25kg of BW. They were fed chaffed wheat straw (45g CP/kg DM) which had been
      molasses sprayed (10%) and pelleted concentrates containing 8.7, 11.7, 14.4 and
      17.6% crude protein (CP) on DM basis, the ratio of straw to concentrate being
      1:5. Kids were fed controlled to satiation in which case small amounts of the
      feeds were offered about five times a day as long as the kids wanted to eat.
      Retention of protein, fat and energy were calculated from their initial and final
      concentrations in the empty body homogenates of the slaughtered kids. With
      increasing CP level in the diet, feed intake increased from 448 to 608g DM/d,
      weight gain from 94 to 181g/d, retention of protein from 9.7 to 27.8g/d,
      retention of fat from 9.6 to 19.1g/d and feed efficiency improved from 4.79 to
      3.39kg DM/kg weight gain. Protein composition of gain increased from 103 to
      154g/kg BWG while fat (103-105g/kg BWG) remained constant. Regression analyses
      showed that BWG can be optimized at 136g CP/kg DM and protein retention at 180g
      CP/kg DM, whereas, dietary nitrogen was utilized most efficiently at 120g CP/kg
      DM. Extrapolated from the regression equations, maintenance N requirement of the
      kids at zero N-retention and at zero BWG were 0.38 and 0.16g N/kg W(0.75),
      respectively. Recommended dietary CP concentrations and maintenance N
      requirements depend on the traits desired.

PMID- 11230961
TI  - Energy level in winter diets of Fallow deer: effect on plasma levels of insulin
      like growth factor-I and sex ratio of their offspring.
AB  - To determine the effect of dietary energy level in the first winter on subsequent
      puberty onset, pregnancy, growth, and secretion of progesterone and insulin-like
      growth factor-I (IGF-I) in Fallow deer, prepubertal deer were fed either a high
      (H) or a low (L) energy diet in a randomised complete block design. June-born
      female Fallow deer were fed ad libitum either 12.5MJ/kg DM (H, n=29) or 10MJ/kg
      DM (L, n=29) in pelleted rations once per day during the winter (approximately 4
      10 months of age) preceding puberty. Blood samples were collected twice weekly
      during the peripubertal period. During the winter feeding period, DM intake was
      similar for both groups but average daily gain was greater (P<0.05) for deer fed
      the H versus L diet. Onset of puberty was not affected (P>0.10) by dietary
      treatment. Concentrations of progesterone in plasma did not differ (P>0.10)
      between dietary treatments before or after puberty, increasing after puberty in
      both groups, and reaching maximal levels 8-12 days after the onset of puberty.
      Concentrations of plasma IGF-I increased (P<0.05) before puberty in both groups
      reaching maximal levels 3-4 days before the onset of puberty but did not differ
      (P>0.10) between H and L diets before or after puberty. Of the 28 does fed the H
      diet that calved, 75% of the calves born were male versus 46% in the L diet
      (P<0.05). In conclusion, increased plasma IGF-I concentrations were associated
      with the onset of puberty in Fallow deer regardless of the level of dietary
      energy intake during the preceding winter. Increased dietary energy during winter
      does not alter pregnancy rates but does alter sex ratio of calves born.

PMID- 11230962
TI  - Effect of substitution of groundnut with high glucosinolate mustard (Brassica
      juncea) meal on nutrient utilization, growth, vital organ weight and blood
      composition of lambs.
AB  - Twenty-four 14-day-old weaner Avivastra (Russian MerinoxNali) male lambs were
      maintained for 180 days on ad libidum Cenchrus (Cenchrus ciliaris) hay and
      concentrate mixture (CM) contained groundnut meal (control) and mustard meal (MM
      group) as major protein source. The two CMs were isonitrogenous (21% CP) and
      isocaloric (2.78McalMEkg(-1) DM), while, CM fed to MM group contained 24.6mg
      glucosinolatesg(-1) DM. Digestibility of nutrients was similar (P>0.05) in the
      two groups except for CP and hemicellulose, which was higher (P<0.05) in control.
      Urinary N loss was higher (P<0.01) in control than in MM group, whereas N
      retention (% of N intake and absorbed) was higher (P<0.01) in MM group compared
      to control. Dry matter (gkg(-1)BW) and glucosinolate intakes were higher in MM
      fed group, whereas DCP and ME intakes were similar (P>0.05) in the two groups.
      Average daily gain (ADG) was, however, 22% higher (P<0.01) in control than in MM
      group. Hemoglobin and albumin contents were lower (P<0.01) in MM group than in
      control. Serum thiocyanate content was 26.7ugg(-1) in MM fed group, while it was
      not detected in control group. Thyroid weight was higher (P<0.01) while liver and
      kidney weights were lower (P<0.01) in MM group. Meat from dissected carcass of
      control group contained more protein and less fat, whereas the reverse was
      noticed in MM group. It is concluded that feeding mustard meal as protein
      supplement reduced growth rate and induced iodine deficiency. Carcass of lambs
      fed mustard meal had more fat and less protein.

PMID- 11230963
TI  - Effect of a controlled-release urea supplement on rumen fermentation in sheep fed
      a diet of sugar cane tops (Saccharum officinarum), corn stubble (Zea mays) and
      King grass (Pennisetum purpureum).
AB  - Four cannulated sheep were used to study ruminal fermentation of a diet
      consisting of 60% sugar cane tops (Saccharum officinarum), 30% corn stubble (Zea
      mays), 10% King grass (Pennisetum purpureum) and 0% (control), 10, 20 or 30%
      controlled-release urea supplement (CRUS) (diets 1, 2, 3 and 4, respectively).
      Average ruminal pH did not differ among diets (P>0.05), but during the first 6h
      of sampling tended to be higher for CRUS diets. Ammonia concentrations were
      higher (P<0.01) in all treatments over controls, indicating microbial protein
      generation. Acetic acid production (mM/1) decreased (P<0.05), propionic acid
      increased (P<0.05), while butyric acid production did not differ among CRUS diets
      and controls (P>0.05). Total amounts of ruminal VFA were lowest (P<0.01) in
      controls, while CRUS diets produced more of these energy sources. Supplementation
      of the high fiber diets with 10, 20 or 30% CRUS increasingly improved rumen
      fermentation, ammonia supply and VFA production. The results show that low
      quality forages (up to 70% DMI) can be used efficiently by sheep when conditions
      for ruminal microorganism are improved with a controlled-release urea supplement.

PMID- 11230964
TI  - Amniocentesis and biochemical evaluation of amniotic fluid in ewes at 70, 100 and
      145 days of pregnancy.
AB  - The objectives of this study were to determine the technical viability of
      amniocentesis in sheep and to observe biochemical changes in the amniotic fluid
      components. Amniotic fluid samples were collected by puncture in the greatest
      curvature of the uterine horn at days 70, 100, and 145 of pregnancy. The surgical
      procedure for collection of amniotic fluid samples was safe and efficient. For
      three stages of pregnancy, the following results were obtained: pH values 8.36,
      7.34 and 7.37; glucose concentrations, 16.06. 8.58, and 3.79g/dl; urea values,
      42.68, 33.53, and 25.49mg/dl; creatinine, 0.85, 5.04, and 11.25g/dl; Gama-GT
      enzyme, 12.58, 14.20, and 12.30UI/l; sodium concentrations, 146.60, 129.42, and
      103.8mmol/l: potassium concentrations, 9.79, 6.15, and 8.65mmol/l; chloride,
      96.59, 85.28, and 65.35mmol/l; total protein, 0.14, 0.23, and 0.24g/dl,
      respectively.

PMID- 11230965
TI  - Effect of different dietary energy level intakes on efficiency of estrus
      synchronization and fertility in Mashona goat does.
AB  - The objective of the study was to determine the effects of three dietary energy
      levels: 0.27 (low level: LL); 0.53 (medium level: ML), and 1.06 (high level: HL)
      MJMEkg(-1)W(0.75) on estrus synchronization and fertility in Mashona goat does.
      Forty-five multiparous Mashona goat does of average bodyweight 19.9+/-2.5kg were
      randomly allocated in equal numbers to the three dietary energy levels. The diets
      were made from a complete feed ration providing 9.83MJMEkg(-1)DM and 15.5% CPkg(
      1)DM. Does were fed initially during a 60-day pre-synchronization period, and
      blood samples were collected twice a week for the determination of plasma
      progesterone concentrations to ascertain ovarian activity. Intramuscular
      injections of cloprostenol (100ug each) were administered 11 days apart.
      Immediately after the second injection of cloprostenol, three fertile bucks were
      introduced to the does and were left with the does for 21 days. The does were
      maintained on their dietary treatments throughout gestation except for those does
      in the LL treatment. Pregnancy was diagnosed 90 days post-mating using an
      ultrasound scanner. After pregnancy diagnosis, does on the LL treatment were
      randomly allocated to ML (n=7) and HL (n=8) treatments. During the pre
      synchronization period, does on the LL treatment lost 12.3% whereas those on ML
      and HL treatments gained 2.1 and 28.8% of their initial bodymasses, respectively.
      The proportion of does exhibiting overt estrus within 96h after the last
      cloprostenol injection was significantly lower (P<0.05) for does on the LL
      treatment (60%) than for those on ML (93%) or HL (100%) treatments, respectively.
      However, based on plasma progesterone concentrations, the percentage of does on
      the LL treatment that exhibited ovarian cycles was numerically lower than that of
      does that were bred (40 versus 73%). Conception, fecundity and twinning rates
      were significantly lower (P<0.05) on the LL treatment than on the ML and HL
      treatments. These results indicate that feeding Mashona goat does 0.27MJMEkg(
      1)W(0.75) compared to 0.53 and 1.06MJMEkg(-1)W(0.75) reduces the expression of
      estrus, conception, fecundity and twinning rates, and that feeding 0.53MJMEkg(
      1)W(0.75) suffices for optimum reproduction. In addition, the results suggest
      that cloprostenol administration may induce ovarian cycles in reproductively
      quiescent does on dietary energy restriction.

PMID- 11230966
TI  - Growth, slaughter and intra-muscular collagen characteristics in Garganica kids.
AB  - Growth performance, ossification of metacarpal growth plate, and intra-muscular
      collagen characteristics in three muscles of 10 intact male Garganica kids were
      studied. Each week, starting from the 47th day of age to slaughter (75th day of
      age), kids were weighed and blood samples taken for plasma non-protein
      hydroxyproline analysis. At slaughter, metacarpal, metatarsal bones and
      metacarpal growth plate thickness were measured. The semitendinosus (ST),
      semimembranosus (SM), and rectus medialis (RM) muscle samples were analysed for
      collagen concentration and hydroxylysyl pyridinoline (HP) cross-links. ST muscle
      had a collagen amount higher than SM and RM (P<0.01), and RM muscle had the
      highest (P<0.01) HP concentration. Tenderness index was the highest (P<0.01) in
      RM muscle. Animal growth rates slowed, starting from 61st day of age (P<0.01);
      this trend coincided with a marked reduction in concentration of plasma non
      protein hydroxyproline (P<0.01). In addition, plasma non-protein hydroxyproline
      concentration was positively correlated (r=0.61, P=0.001) with growth rate of
      animals, suggesting that collagen turnover decreases during a slow growth phase.
      Based on the metacarpal growth plate width, the rate of bone ossification appears
      to be slower in goats than sheep.

PMID- 11230967
TI  - Adenosine as an important mediator of post-ischaemic neuronal stunning.

PMID- 11230968
TI  - Continuing insights into the heart as an endocrine organ: adrenomedullin and
      cardiac fibroblasts.

PMID- 11230969
TI  - Abnormalities in L-arginine transport and nitric oxide biosynthesis in chronic
      renal and heart failure.
AB  - Patients with chronic renal and heart failure present with hypertension and
      widespread vasoconstriction, respectively. Although systemic release of nitric
      oxide (NO) may be elevated in both pathological syndromes, enhanced production of
      NO fails to overcome endothelial dysfunction. Plasma concentrations of L
      arginine, a cationic amino acid precursor for NO synthesis, are reduced whilst
      levels of the endogenous L-arginine analogues, asymmetric and symmetric dimethyl
      arginine and N(G)-monomethyl-L-arginine, seem to be elevated. We have reported
      that transport of L-arginine via the cationic amino acid transporters y(+)/CAT
      and/or y(+)L are up-regulated in erythrocytes, peripheral blood mononuclear cells
      and platelets from both patients with either chronic renal or heart failure. A
      possible explanation why NO serves as a failing counter-regulatory mechanism in
      both these pathologies is that availability of L-arginine for NO production is
      reduced despite the observed increase in membrane transport. This review examines
      the mechanisms underlying alterations in NO production in chronic renal and heart
      failure, and the possible role of L-arginine transport in vascular and platelet
      dysfunction observed in both syndromes.

PMID- 11230970
TI  - Adenosine inhibits norepinephrine release in the postischemic rat heart: the
      mechanism of neuronal stunning.
AB  - OBJECTIVE: Numerous studies support the concept of impaired postischemic
      sympathetic neurotransmission in the heart. We hypothesized that postischemic
      neuronal dysfunction (neuronal stunning) is caused by a transient suppression of
      exocytotic norepinephrine (NE) release from sympathetic nerve terminals.
      Furthermore, we assessed the role of presynaptic adenosine-receptors and alpha2
      adrenoceptors in neuronal stunning. METHODS AND RESULTS: Exocytotic NE release
      was induced by two electrical field stimulations (S(1) and S(2)) in isolated
      perfused rat hearts. S(1) was performed under baseline conditions and S(2) either
      during or following intervention. Results are expressed as mean S(2)/S(1)
      ratios+/-S.E.M. Stepwise increase of global ischemic periods (10, 20, and 30 min)
      induced a progressive suppression of NE release in the postischemic hearts, which
      was reversible during reperfusion. Both the degree and duration of NE suppression
      was dependent on the extent of the preceding ischemic period. Following 10-min
      ischemia complete recovery of NE release was achieved after 5-min reperfusion
      (1.07+/-0.12), whereas 5-min reperfusion did not restore NE release after 30 min
      (0.36+/-0.07) of ischemia. The adenosine-receptor antagonists 8
      phenyltheophylline (8-PT; non-selective) and 8-cyclopentyl-1,3-dipropylxanthine
      (DPCPX; adenosine A1-receptor subtype selective) significantly increased NE
      release after 30-min ischemia and 5-min reperfusion (0.78+/-0.06 and 0.64+/
      0.07), while in the same experimental protocol blockade of alpha2-adrenoceptors
      by yohimbine failed to restore the postischemic release (0.24+/-0.06). In non
      ischemic hearts the adenosine analogue R(-)N(6)-(2-phenylisopropyl)adenosine (R
      PIA) resulted in a marked suppression of NE release (0.61+/-0.07). The inhibitory
      effect of R-PIA and 2-chloro-N(6)-cyclopentyladenosine (CCPA; adenosine A1
      receptor subtype selective agonist) persisted 5 min after cessation of R-PIA
      (0.62+/-0.05) and CCPA (0.58+/-0.04). Activation of alpha2-adrenoceptors by 5
      bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK 14,304) also caused
      a reduction of NE release (0.50+/-0.02), but the release increased to control
      levels 5 min after cessation of UK 14,304 (0.90+/-0.06). CONCLUSIONS: The results
      establish the phenomenon of neuronal stunning in terms of a postischemic
      suppression of exocytotic NE release and provide evidence that neuronal stunning
      is mediated by endogenous adenosine through activation of presynaptic adenosine
      A1-receptors.

PMID- 11230971
TI  - Cardiac fibroblasts are major production and target cells of adrenomedullin in
      the heart in vitro.
AB  - OBJECTIVE: Adrenomedullin (AM) is a potent vasodilator peptide. Plasma AM
      concentration is increased in patients with various heart diseases, and both
      myocytes (MCs) and non-myocytes (NMCs) secrete AM and express its receptors.
      These facts suggest that cardiac cells possess an autocrine/paracrine capability
      mediated by AM. METHODS: MCs and NMCs were prepared from cardiac ventricles of
      neonatal rats. AM and endothelin-1 concentrations were measured by
      radioimmunoassays, and interleukin-6 level by a specific bioassay. Total
      nitrite/nitrate contents were measured with a fluorescence assay kit. RESULTS: A
      basal secretion rate of AM from NMCs was 2.8-fold higher than that from MCs.
      Interleukin-1beta, tumor necrosis factor-alpha and lipopolysaccharide stimulated
      AM secretion from NMCs but not from MCs. AM stimulated interleukin-6 production
      in the presence of these cytokines or lipopolysaccharide, which was more
      prominent in NMCs. In the presence of interleukin-1beta, AM augmented nitric
      oxide synthesis 2.7-fold in NMCs, but slightly in MCs. NMCs secreted endothelin-1
      at a rate nine times higher than MCs, and AM inhibited endothelin-1 secretion
      from NMCs. CONCLUSION: This in vitro study suggests that AM in the heart is
      mainly produced in NMCs and exerts its effects through NMCs, especially under
      inflammatory conditions.

PMID- 11230972
TI  - Down-regulation of Akt/PKB in senescent cardiac fibroblasts impairs PDGF-induced
      cell proliferation.
AB  - OBJECTIVE: Cardiovascular diseases are the leading cause of death in the Western
      World, especially in the elder population. One pathophysiological component of
      cardiovascular disease is myocardial fibrosis, primarily derived from cardiac
      fibroblasts. Here we investigated the regulation of proliferation of fibroblasts
      from hearts of adult rats by platelet derived growth factor AA (PDGF-AA).
      METHODS: Cardiac fibroblasts were isolated from adult Wistar rats. PDGF-induced
      cell proliferation was analysed by FACS. PDGF-receptor numbers were analysed by
      receptor binding assays. Using differential display, differentially expressed
      kinases were identified during ageing in vitro and confirmed by Northern and
      Western blotting. Transient overexpression of IRES-GFP constructs was used to
      analyse the role of the akt kinase on proliferation by FACS. RESULTS: During in
      vitro senescence/aging of primary fibroblasts, the growth response to PDGF-AA was
      greatly reduced without alterations in its receptor number or affinity and
      without changes in downstream signalling via the MAP-kinase pathway. By using a
      differential display strategy selective for protein kinases, we identified
      reduced expression of Akt-1 kinase (PKB-alpha) in senescent rat cardiac
      fibroblasts. These findings were supported by data showing reduced expression of
      Akt-1 in heart samples from old humans. Overexpression of activated Akt-1 almost
      completely reconstituted PDGF-AA dependent cell proliferation in aged
      fibroblasts. CONCLUSION: These results support an important role for Akt in
      senescence and regulation of cardiac fibroblast cell proliferation.

PMID- 11230973
TI  - Methods of collecting and evaluating non-clinical cardiac electrophysiology data
      in the pharmaceutical industry: results of an international survey.
AB  - OBJECTIVE: To assess current practice in the pharmaceutical industry for
      assessing the potential for QT interval prolongation by non-cardiovascular
      medicinal products. METHODS: The survey was based on responses from the
      Toxicology and (Safety) Pharmacology laboratories (a total of 74 laboratories) of
      54 companies based in Europe, Japan/Asia and the USA, received between January
      and March 1999. RESULTS: All 54 companies conducted preclinical in vivo
      electrocardiography (EGG) evaluation of new active substances (NASs). Thirty of
      these companies also conducted in vitro cardiac electrophysiology studies on
      their compounds. The majority of in vivo work was done in conscious beagle dogs.
      There was no consistency within the industry in defining the magnitude of change
      in QT interval that is considered biologically important. Most companies
      considered a change greater than 10% to be important, although the design of the
      studies suggested that group sizes used may not give sufficient statistical power
      to detect this size of change. Bazett's formula was used by 41% of laboratories
      to correct QT for changes in heart rate, despite the fact that this formula is
      generally deemed to be unsuitable for use in dogs. For studies in anaesthetised
      dogs, the majority of laboratories used barbiturate anaesthesia, but researchers
      should be aware of the effects of this and some other anaesthetic agents on QT
      interval. As for in vitro cardiac electrophysiology, there was wide diversity in
      the testing methodologies, particularly with regard to the test species and
      tissue type. As with QT prolongation, there was no consensus on the degree of
      action potential prolongation to cause concern. For both in vitro and in vivo
      testing, the majority of companies tested a minimum of three dose (or
      concentration) levels in order to ascertain any dose-response relationship.
      CONCLUSIONS: The survey provides a snapshot of the practice in the industry prior
      to any internationally-agreed consensus on the most effective and efficient
      approaches to minimising the risk of QT prolongation by new drugs in man. It must
      be stated that for any given methodology, the 'majority view' in the industry is
      not necessarily best practice.

PMID- 11230974
TI  - Intracellular calcium changes and tachycardia-induced contractile dysfunction in
      canine atrial myocytes.
AB  - OBJECTIVES: Indirect evidence suggests a role for Ca(2+)-overload in electrical
      and mechanical alterations caused by atrial tachycardia. The present study
      assessed the alterations in cellular [Ca(2+)] and contractile function caused by
      rapid atrial cellular activation. METHODS: Intracellular Ca(2+) transients (CaT)
      and cell shortening (CS) were measured by microfluorometry (Indo-1 AM) and video
      edge-detection in isolated, field-stimulated canine atrial myocytes (37 degrees
      C). RESULTS: Abrupt increases in frequency (0.3-3 Hz) caused rapid increases in
      diastolic [Ca(2+)]i (DCa) that were maintained during rapid-pacing for up to 50
      min. When short-term (3-min) rapid-pacing was imposed, CaT and CS increased
      initially upon returning to 0.3 Hz, but then declined rapidly to 64+/-5 and 49+/
      7%, respectively, of pre-tachycardia values, returning to control after
      approximately 15 min. Post-tachycardia CaT and CS reductions were prevented by
      decreasing [Ca(2+)]o during tachycardia to prevent Ca(2+)-overload. CS reductions
      correlated with indices of Ca(2+) loading during tachycardia. Restoration of CaT
      to normal during post-tachycardia contractile dysfunction (by increasing
      [Ca(2+)]o) returned CS to normal, indicating that reduced Ca(2+) release, not
      reduced myofilament Ca(2+)-sensitivity, caused post-tachycardia contractile
      failure. Estimation of sarcoplasmic-reticulum Ca(2+)-stores (caffeine-induced
      Ca(2+)-release) confirmed tachycardia-induced Ca(2+)-loading and suggested that
      reduced Ca(2+)-stores decreased Ca(2+)-release post-tachycardia. CONCLUSIONS:
      Atrial tachycardia increases cellular Ca(2+)-loading, leading to post-tachycardia
      abnormalities in Ca(2+)-handling that produce contractile dysfunction. These
      findings are the first direct evidence for the frequently-postulated role of
      Ca(2+)-overload in tachycardia-induced abnormalities of atrial function.

PMID- 11230975
TI  - Differential efficacy of L- and T-type calcium channel blockers in preventing
      tachycardia-induced atrial remodeling in dogs.
AB  - BACKGROUND: Tachycardia-induced remodeling likely plays an important role in
      atrial fibrillation (AF) maintenance and recurrence after cardioversion, and
      Ca(2+) overload may be an important mediator. This study was designed to evaluate
      the relative efficacies of selective T-type (mibefradil) and L-type (diltiazem)
      Ca(2+)-channel blockers in preventing tachycardia-induced atrial remodeling.
      METHODS: Dogs were given daily doses of mibefradil (100 mg), diltiazem (240 mg)
      or placebo in a blinded fashion, beginning 4 days before and continuing through a
      7-day period of atrial pacing at 400 bpm. An electrophysiological study was then
      performed to assess changes in refractoriness, refractoriness heterogeneity and
      AF duration. RESULTS: Mean duration of burst-pacing induced AF was similar in
      placebo (567+/-203 s) and diltiazem-treated (963+/-280 s, P=NS) animals, but was
      much less in mibefradil-treated dogs (3.6+/-0.9 s, P<0.002) and non-paced
      controls (6.6+/-2.7 s). In contrast to mibefradil, diltiazem did not alter
      tachycardia-induced refractoriness abbreviation or heterogeneity. To exclude
      inadequate dosing as an explanation for diltiazem's inefficacy, we studied an
      additional group of dogs treated with 720 mg/day of diltiazem, and again noted no
      protective effect. Acute intravenous administration of diltiazem to control dogs
      failed to alter atrial refractoriness or AF duration, excluding a masking of
      remodeling suppression by offsetting profibrillatory effects of the drug.
      CONCLUSIONS: Whereas the selective T-type Ca(2+)-channel blocker mibefradil
      protects against atrial remodeling caused by 7-day atrial tachycardia, the
      selective L-type blocker diltiazem is without effect. These findings are
      potentially important for understanding the mechanisms and prevention of
      clinically-relevant atrial-tachycardia-induced remodeling.

PMID- 11230976
TI  - Remodeling by ventricular pacing in hypertrophying dog hearts.
AB  - OBJECTIVE: Asynchronous electrical activation of the left ventricle (LV), induced
      by ventricular pacing (VP), reduces mechanical load in early- and enhances it in
      late-activated regions. Consequently, chronic VP leads to asymmetric hypertrophy.
      We investigated whether such locally induced myocardial hypertrophy also occurs
      in the presence of pressure overload hypertrophy (POH). METHODS: POH was induced
      by aortic banding in puppies. At age 9 months, seven dogs were paced at the right
      ventricular (RV) apex at physiological heart rate for 6 months (POH-pace group),
      while four POH dogs served as POH-control group. Changes in volume of the LV
      cavity and the total LV wall and of five LV wall sectors were measured by means
      of 2D-echocardiography and X-ray marker detection. RESULTS: During the last 6
      months of the protocol the volume of the five LV wall sectors increased in the
      POH-control group, ranging from 27+/-9 to 30+/-5% (mean+/-S.D.). In POH-pace
      animals sector wall volume in the four sectors at intermediate to long distance
      from the pacing site increased to a similar extent (ranging from 31+/-16 to 35+/
      17%), but wall volume in the early-activated apical septum increased
      significantly less (17+/-21%). In these hearts myocyte diameter was significantly
      smaller in the apical septum than in the lateral LV wall. The regional difference
      in wall volume changes (19+/-21%) was significantly smaller in the POH-pace group
      than in chronically paced, non-hypertrophic, canine hearts in a previous study
      from our laboratory (43+/-14%). CONCLUSIONS: In hypertrophying hearts chronic
      pacing at the RV apex suppresses the development of hypertrophy in the early
      activated apical septum but does not cause additional hypertrophy in late
      activated regions, as is the case in non-hypertrophic hearts. The latter suggests
      that the local growth response is reduced in hypertrophying hearts.

PMID- 11230977
TI  - Transient outward current modulates discontinuous conduction in rabbit
      ventricular cell pairs.
AB  - OBJECTIVE: While several studies have demonstrated that the L-type calcium
      current maintains discontinuous conduction, the contribution of the transient
      outward current (I(to)) to conduction remains unclear. This study evaluated the
      effects of I(to) inhibition on conduction between ventricular myocytes. METHODS:
      An electronic circuit with a variable resistance (R(j)) was used to electrically
      couple single epicardial myocytes isolated from rabbit right ventricle. We
      inhibited I(to) with 4-aminopyridine superfusion, rate-acceleration, or premature
      stimulation to evaluate the subsequent effects on conduction delay and the
      critical R(j), which was quantified as the highest R(j) that could be imposed
      before conduction failed. RESULTS: I(to) inhibition significantly enhanced
      conduction in all cell pairs (n=23). Pharmacologic inhibition of I(to) resulted
      in a 32+/-5% decrease in conduction delay and a 36+/-7% increase in critical
      R(j). Similarly, reduction of the basic cycle length from 2 to 0.5 s resulted in
      a 31+/-3% decrease in conduction delay and a 31+/-3% increase in critical R(j).
      Finally, premature action potentials conducted with a 41+/-4% shorter conduction
      delay and a 73+/-24% higher critical R(j) than basic action potentials.
      CONCLUSIONS: I(to) inhibition significantly enhanced conduction across high R(j).
      These results suggest I(to) may contribute to rate-dependent conduction
      abnormalities.

PMID- 11230978
TI  - The slow component of the delayed rectifier potassium current in undiseased human
      ventricular myocytes.
AB  - OBJECTIVE: The purpose of this study was to investigate the properties of the
      slow component of the delayed rectifier potassium current (I(Ks)) in myocytes
      isolated from undiseased human left ventricles. METHODS: The whole-cell
      configuration of the patch-clamp technique was applied in 58 left ventricular
      myocytes from 15 hearts at 37 degrees C. Nisoldipine (1 microM) was used to block
      inward calcium current (I(Ca)) and E-4031 (1-5 microM) was applied to inhibit the
      rapid component of the delayed rectifier potassium current (I(Kr)). RESULTS: In
      31 myocytes, an E-4031 insensitive, but L-735,821 and chromanol 293B sensitive,
      tail current was identified which was attributed to the slow component of I(K)
      (I(Ks)). Activation of I(Ks) was slow (tau=903+/-101 ms at 50 mV, n=14), but
      deactivation of the current was relatively rapid (tau=122.4+/-11.7 ms at -40 mV,
      n=19). The activation of I(Ks) was voltage independent but its deactivation
      showed clear voltage dependence. The deactivation was faster at negative voltages
      (about 100 ms at -50 mV) and slower at depolarized potentials (about 300 ms at 0
      mV). In six cells, the reversal potential was -81.6+/-2.8 mV on an average which
      is close to the K(+) equilibrium potential suggesting K(+) as the main charge
      carrier. CONCLUSION: In undiseased human ventricular myocytes, I(Ks) exhibits
      slow activation and fast deactivation kinetics. Therefore, in humans I(Ks)
      differs from that reported in guinea pig, and it best resembles I(Ks) described
      in dog and rabbit ventricular myocytes.

PMID- 11230979
TI  - Peroxynitrite induced nitration and inactivation of myofibrillar creatine kinase
      in experimental heart failure.
AB  - OBJECTIVE: Oxidative stress is implicated in the initiation and progression of
      congestive heart failure, but the putative reactive species and cellular targets
      involved remain undefined. We have previously shown that peroxynitrite (ONOO(-),
      an aggressive biological oxidant and nitrating agent) potently inhibits
      myofibrillar creatine kinase (MM-CK), a critical controller of contractility
      known to be impaired during heart failure. Here we hypothesized that nitration
      and inhibition of MM-CK participate in cardiac failure in vivo. METHODS: Heart
      failure was induced in rats by myocardial infarction (left coronary artery
      ligation) and confirmed by histological analysis at 8 weeks postinfarct (1.3+/
      1.4 vs. 37.7+/-3.2% left ventricular circumference; sham control vs. CHF, n=10
      each). RESULTS: Immunohistochemistry demonstrated significantly increased protein
      nitration in failing myocardium compared to control (optical density: 0.58+/-0.06
      vs. 0.93+/-0.09, sham vs. CHF, P<0.05). Significant decreases in MM-CK activity
      and content were observed in failing hearts (MM-CK k(cat): 6.0+/-0.4 vs. 3.0+/
      0.3 micromol/nM M-CK/min, P<0.05; 6.8+/-1.3 vs. 4.7+/-1.2% myofibrillar protein,
      P<0.05), with no change in myosin ATPase activity. In separate experiments,
      isolated rat cardiac myofibrils were exposed to ONOO(-) (2-250 microM) and enzyme
      studies were conducted. Identical to in vivo studies, selective reductions in MM
      CK were observed at ONOO(-) concentrations as low as 2 microM (IC(50)=92.5+/-6.0
      microM); myosin ATPase was unaffected with ONOO(-) concentrations as high as 250
      microM. Concentration dependent nitration of MM-CK occurred and extent of
      nitration was statistically correlated to extent of CK inhibition (P<0.001).
      Immunoprecipitation of MM-CK from failing left ventricle yielded significant
      evidence of tyrosine nitration. CONCLUSION: These data demonstrate that cardiac
      ONOO(-) formation and perturbation of myofibrillar energetic controllers occur
      during experimental heart failure; MM-CK may be a critical cellular target in
      this setting.

PMID- 11230980
TI  - Modulation of cardiac natriuretic peptide gene expression following endothelin
      type A receptor blockade in renovascular hypertension.
AB  - OBJECTIVE: Increased expression of the cardiac natriuretic peptides (NP), atrial
      natriuretic factor (ANF) and brain natriuretic peptide (BNP) is observed during
      chronic hemodynamic overload. The mechanisms underlying this process are not
      fully understood. In vitro, endothelin 1 (ET-1) is a powerful stimulator of
      cardiac NP and, therefore, has been assumed to be one possible mediator of
      increased NP gene expression following chronic pressure or volume overload. In
      the present work we investigated the possible role of ET-1 in mediating the
      observed upregulation of cardiac NP in two kidney-one clip (2K-1C) Goldblatt
      hypertensive rats treated for 6 weeks with the ET-1 type A (ET(A)) receptor
      subtype receptor antagonist ABT-627. METHODS: 2K-1C hypertension was induced in
      male Sprague-Dawley rats weighing 100-125 g by placing a silver clip (internal
      diameter 0.25 mm) around the left renal artery through a flank incision. The
      right kidney was left undisturbed. Sham operated rats underwent the same
      experimental procedures but no clip was placed on the left renal artery. ABT-627
      was administered (10 mg/kg per day) in the drinking water for 6 weeks. RESULTS:
      In hypertensive rats, ABT-627 prevented a further rise in blood pressure
      beginning at 3 weeks after clipping and reduced the ventricular hypertrophy
      observed at the end of the experiment. ET(A) blockade prevented enhanced NP gene
      expression in the right ventricle and partially prevented it in the left
      ventricle. No modifications in atrial NP gene expression were observed in either
      control or 2K-1C animals. ET(A) blockade decreased BNP circulating levels but did
      not affect ANF plasma levels in clipped rats. ABT-627 increased alpha-myosin
      heavy chain gene expression and decreased the abundance of the beta isoform
      transcript. CONCLUSION: The results obtained in the present investigation show
      the participation of ET-1 in the increased expression of ventricular NP in 2K-1C
      renovascular hypertension and an apparent lack of effect of ET(A) blockade on
      atrial NP gene expression in both control and hypertensive animals thus showing
      that in vivo, atrial and ventricular NP gene expression are differentially
      regulated.

PMID- 11230981
TI  - Dual natriuretic peptide response to volume load in the fetal circulation.
AB  - OBJECTIVE: To measure atrial natriuretic peptide (ANP) and brain natriuretic
      peptide (BNP) in control fetuses and fetuses with Rhesus isoimmunisation before
      and after intravascular transfusion. The current study was designed to
      investigate the response of ANP and BNP to cardiac short-term and long-term
      volume load in the human fetus. METHODS: Fetal blood samples were collected from
      18 human fetuses (nine controls, nine anemic fetuses with Rhesus isoimmunisation
      before and after intravascular transfusion). Fetal ANP and BNP concentrations
      were measured and compared to maternal plasma levels. RESULTS: Both ANP and BNP
      were significantly higher in fetal blood compared to the mothers. Fetuses with
      Rhesus isoimmunisation, characterized by long-term cardiac overload, showed
      significantly elevated ANP but not BNP concentration compared to the fetal
      controls (ANP: 80.8+/-16.6 vs. 31.6+/-7.7 pg/ml, P<0.05). However, short-term
      volume load due to intravascular transfusion leads to a significant increase in
      the fetal BNP- but not ANP-plasma level (BNP: 112.9+/-14.1 vs. 64.8+/-6.6 pg/ml,
      P<0.05). CONCLUSION: ANP and BNP respond differently to cardiac short- and long
      term volume load in the fetal circulation. Therefore, the data suggest that in
      the fetus, similar to adults, ANP and BNP constitute a dual natriuretic peptide
      system responsive to changes in cardiac filling pressure.

PMID- 11230982
TI  - Association between a polymorphism in the G protein beta3 subunit gene (GNB3)
      with arterial hypertension but not with myocardial infarction.
AB  - OBJECTIVE: A polymorphism at position 825(C-->T) of the G protein beta3 (GNB3)
      gene was found to be associated with enhanced transmembrane signalling as well as
      with an increased prevalence of arterial hypertension. The aim of the present
      study was to further investigate the association of the GNB3 C825T allele status
      with arterial hypertension in a large population-based sample and its association
      with specific end organ damage, i.e. myocardial infarction (MI). METHODS:
      Individuals from a population-based sample (n=2052) and patients suffering from
      premature MI (age at first MI < or = 60 years, n = 606) were studied by
      questionnaire as well as by physical examination and biochemical analyses.
      RESULTS: In the population-based sample, the prevalence of arterial hypertension
      (blood pressure > or = 160/95 mmHg and/or antihypertensive medication) was higher
      in individuals with the TT genotype (41.8%) as compared to heterozygote
      individuals (36.6%) or those with the CC genotype (32.75%) (P = 0.02). This
      association was predominantly found in men. Moreover, men without
      antihypertensive medication carrying the TT genotype showed higher diastolic
      blood pressure than those carrying the CC genotype (86.5 vs. 83.7 mmHg, P =
      0.04). However, the genotype distribution and the allele frequencies were similar
      in both, the population-based and the MI patient sample. Furthermore, neither the
      age at the time of MI nor the location of the MI were related to the genotype
      distribution. Similarly, gender and age stratified analyses did not show any
      association of the GNB3 genotype and MI. CONCLUSIONS: In male individuals from a
      large population-based sample, the T allele of the GNB3 polymorphism was
      associated with arterial hypertension. However, the effects of the GNB3 825T
      allele on blood pressure were small and did not translate to a clinically
      relevant increase of risk for MI.

PMID- 11230983
TI  - Signalling mechanisms underlying the myogenic response in human subcutaneous
      resistance arteries.
AB  - OBJECTIVE: In this study we have examined for the first time the signal
      transduction mechanisms involved in the generation of pressure-dependent myogenic
      tone in human small resistance arteries from the subcutaneous vascular bed.
      METHODS: Myogenic responses and the subcellular mechanisms involved in the
      generation of this response were studied on a pressure myograph. RESULTS AND
      CONCLUSION: Human subcutaneous resistance arteries constricted 14.1+/-1.1% in
      response to an increases in intraluminal pressure from 40 to 80 mmHg and a
      further 3.5+/-1.7% in response to the 80-120-mmHg pressure step. Ca(2+) depletion
      or nifedipine abolished this response, whereas BAY K 8644 increased this response
      to 20.6+/-2.1% (P<0.05, response vs. control). The phospholipase C inhibitor U
      73122 reduced the myogenic response to 2.5+/-1.0% at 80 mmHg (P<0.01, response
      vs. control) and abolished it at 120 mmHg. Diacylglycerol lipase inhibition with
      RHC-80267 abolished all myogenic responses to pressure. The protein kinase C
      (PKC) activator phorbol 12,13-dibutyrate increased the maximal myogenic response
      to 20.9+/-1.8% (P<0.05, response vs. control), whereas the PKC inhibitor
      calphostin C abolished myogenic responses. These data show that the generation of
      pressure-dependent myogenic tone in human subcutaneous arteries is dependent on
      Ca(2+) influx via voltage operated Ca(2+) channels (VOCCs) and a concomitant
      requirement for the activation of phospholipase C (PLC), diacylglycerol, and PKC.

PMID- 11230984
TI  - Inhibition by leukocyte depletion of neointima formation after balloon
      angioplasty in a rabbit model of restenosis.
AB  - OBJECTIVE: The aim of the current study was to examine neointima formation in
      balloon injured left subclavian artery of rabbits subjected to two different
      methods of leukocyte depletion at the time of injury. METHODS: Angioplasty of the
      left subclavian artery was performed in leukopenic male New Zealand White
      rabbits. Depletion of circulating leukocytes was induced by either mustine
      hydrochloride or an antibody against leukocyte common antigen (anti-LCA) before
      angioplasty. Left and right subclavian arteries were removed 28 days after injury
      for morphological analysis and measurement of neointimal size. At the same time,
      leukocytes were isolated from autologous rabbit blood for 51Cr-labelling for
      assessment of leukocyte adhesion to injured and non-injured artery segments.
      RESULTS: Leukopenia decreased neointima formation in injured arteries (neointimal
      area was 0.09+/-0.03 mm(2) in mustine-treated arteries, n=8, vs. 0.56+/-0.07
      mm(2) in control arteries, n=7; P<0.001 and 0.07+/-0.01 mm(2) in anti-LCA treated
      arteries, n=9, vs. 0.22+/-0.04 mm(2) in non immune serum-treated arteries, n=9;
      P<0.001). Adventitial fibrosis was also significantly (P<0.05) decreased by both
      leukopenic interventions. Neither medial nor adventitial area was modified in any
      of the groups. No differences in leukocyte adhesion were observed between injured
      and non-injured arteries in any of the experimental groups at the 28 day time
      point. CONCLUSION: These results suggest that leukocytes play a major role in the
      development of two of the major characteristics of the response to balloon
      injury, namely formation of neointima and adventitial fibrosis, that currently
      limit the success of clinical angioplasty. Elucidation of the fine mechanisms
      involved in leukocyte-mediated injury may lead to the discovery of novel
      therapeutic targets for the prevention of restenosis.

PMID- 11230985
TI  - All-trans retinoic acid regulates proliferation, migration, differentiation, and
      extracellular matrix turnover of human arterial smooth muscle cells.
AB  - OBJECTIVE: The vitamin-A derivative all-trans retinoic acid (atRA) is a potent
      regulator of cell growth, differentiation, and matrix formation of various cell
      types and plays an important role in embryogenesis. However, sparse data are
      available about its effects on human vessel diseases. Thus, we studied the
      effects of atRA on human arterial smooth muscle cell (haSMC) and endothelial cell
      (haEC) proliferation, migration, differentiation and extracellular matrix (ECM)
      turnover in mono- and transfilter cocultures. METHODS: Effects of atRA on human
      arterial cells in monocultures were determined using cell counting assays, BrdU
      ELISA and MTT-tests. In transfilter cocultures haSMC-growth was studied under the
      stimulatory effect of proliferating haEC. Using Northern blot analysis, effects
      of atRA on mRNA expression of ECM-proteins were examined while protein expression
      and activity of matrix metalloproteinases were determined by Western blotting and
      zymography. RESULTS: atRA caused a dose dependent inhibition of haSMC-growth in
      monocultures (IC(50) at 0.022 microM) whereas haEC-growth was inhibited less
      potently (IC(50) at 97 microM). In addition, proliferation and migration of haSMC
      through a porous membrane were inhibited dose dependently by micromolar atRA
      doses after non-stop and single dose application of atRA on the endothelial side
      of the complex transfilter coculture system. Immunostainings and Northern
      blotting demonstrated an enhanced alpha-smooth muscle actin and heavy chain
      myosin expression in haSMC after atRA-treatment. Whereas mRNA-expression of the
      glycoproteins thrombospondin-1 and fibronectin were decreased, collagen-1 mRNA
      expression was even slightly stimulated. Transcription of biglycan and TGF-beta1
      were not influenced in a specific manner. Finally, protein expression and
      activity of the matrix metalloproteinases MMP-2 and MMP-9 were inhibited
      significantly by atRA. CONCLUSIONS: atRA was found to be a potent inhibitor of
      both haSMC-proliferation and -migration, even in coculture with haEC releasing
      growth factors. In addition, redifferentiation, ECM synthesis and ECM degradation
      were regulated by atRA which also influence haSMC migration and intima formation.
      Thus, atRA-treatment seems to be a promising strategy for the inhibition of
      processes involved both in atherosclerosis and restenosis.

PMID- 11230986
TI  - Pivotal role of tyrosine phosphatase SHP-1 in AT2 receptor-mediated apoptosis in
      rat fetal vascular smooth muscle cell.
AB  - OBJECTIVE: To examine the possible crosstalk and the roles of angiotensin (Ang)
      II type 1 (AT1) and type 2 (AT2) receptors in the control of apoptosis in fetal
      vascular smooth muscle cells (VSMCs). METHODS: Fetal VSMCs were prepared from rat
      fetal aorta at embryonic day 20. Expression of Ang II receptors was measured by a
      radioligand binding assay. Apoptotic changes were assessed by caspase 3 activity
      and chromatin dye staining. Regulation of extracellular signal-regulated kinase
      (ERK) activity via Ang II receptors was analysed by determining phosphorylated
      ERK with Western blot. Ang II receptor-mediated activation of tyrosine
      phosphatase SHP-1 was assessed by protein tyrosine phosphatase assay. RESULTS:
      The expression of AT1 and AT2 receptors was approximately 70%: 30% per cell.
      Serum depletion induced apoptosis in fetal VSMCs and selective AT1 receptor
      stimulation attenuated the apoptotic changes, whereas selective AT2 receptor
      activation enhanced apoptosis. Ang II increased ERK phosphorylation, which was
      inhibited by addition of the AT1 receptor-specific antagonist CV11974, but
      enhanced by addition of the AT2 receptor-specific antagonist PD123319, suggesting
      that activation of AT2 receptor attenuated the AT1 receptor-mediated ERK
      phosphorylation. Moreover, we demonstrated that AT2 receptor stimulation
      activated SHP-1 in fetal VSMCs, whereas AT1 receptor stimulation did not.
      Transient transfection of a dominant-negative SHP-1 mutant into rat fetal VSMCs
      resulted in a significant decrease of the AT2 receptor-mediated inhibition of ERK
      phosphorylation and attenuated the proapoptotic effect of AT2 receptor.
      CONCLUSION: These results indicate that a crosstalk between AT1 and AT2 receptors
      regulates the survival of fetal VSMCs and substantiate SHP-1 as a key molecule in
      AT2 receptor signaling.

PMID- 11230987
TI  - The angiopoietin-tie2 system in coronary artery endothelium prevents oxidized low
      density lipoprotein-induced apoptosis.
AB  - OBJECTIVES: A healthy, intact coronary artery endothelium is important because
      most common coronary artery diseases result from loss of endothelial integrity.
      In this study, we explored the biological significance of the angiopoietin-Tie2
      system in porcine coronary artery. METHODS: Cultured porcine coronary artery
      endothelial cells and explanted coronary arteries were used. RESULTS:
      Immunohistochemical analyses indicated that Ang1 is selectively expressed in
      vascular muscular cells, whereas angiopoietin-2 (Ang2) and Tie2 are selectively
      expressed in endothelial cells. Accordingly, Ang1 mRNA is mainly expressed in
      cultured porcine coronary artery vascular smooth muscle cells, whereas Ang2 and
      Tie2 mRNAs are mainly expressed in cultured porcine coronary artery endothelial
      cells (PCAECs). Ang1 (200 ng/ml) induced Tie2 phosphorylation, while Ang2 (200
      ng/ml) did not produce Tie2 phosphorylation. Ang1 increased the survival of
      cultured PCAECs during apoptosis induced by oxidized low-density lipoprotein
      (OxLDL). This survival effect was does-dependent and PI. Furthermore, Ang1 also
      protected endothelial cells of explanted coronary artery against OxLDL-induced
      apoptosis artery. CONCLUSION: These results suggest that adult coronary artery
      contains Ang1-Tie2 components that enhance endothelial cell survival to help
      maintain the normal integrity of the coronary artery endothelium.

PMID- 11230988
TI  - Effects of interleukin-10 on monocyte/endothelial cell adhesion and MMP-9/TIMP-1
      secretion.
AB  - OBJECTIVE: Monocyte adhesion to endothelial cells and subsequent secretion of
      matrix metalloproteinases (MMPs) by activated macrophages are key events in
      arteriosclerosis and restenosis. We tested the hypothesis that interleukin-10 (IL
      10), a potent anti-inflammatory cytokine, inhibits monocyte-endothelial cell
      interactions. METHODS: The effect of IL-10 on monocyte/endothelial cell adhesion,
      as well as on the expression of MMP-9 and the tissue inhibitor of MMP-9, TIMP-1,
      were first tested in vitro in coculture systems. In addition, we used an ex vivo
      binding assay to study the inhibitory effect of IL-10 on monocyte adhesion to
      carotid arteries obtained from either normal, or L-nitro arginine-methyl ester (L
      NAME)-treated rats. The effect of IL-10 on the expression of monocyte adhesion
      molecules (CD18 and CD62-L) was studied by flow cytometry. RESULTS: IL-10 (150
      ng/ml) inhibits monocyte adhesion to endothelial cells (by 35%) and to carotid
      arteries (by 40 and 50%, in normal and L-NAME-treated rats, respectively), via
      direct modulation of the expression of CD18 and CD62-L. Moreover, IL-10 dose
      dependently decreases MMP-9 activity and increases TIMP-1 levels in coculture
      systems, both at the transcriptional level. CONCLUSIONS: Our results suggest that
      IL-10 is an important modulator of monocyte-endothelial cell interactions.

PMID- 11230989
TI  - A common genetic variant of luteinizing hormone; relation to normal and aberrant
      pituitary-gonadal function.
AB  - Mutations of the luteinizing hormone (LH) subunit genes are extremely rare. Only
      one polymorphic LHbeta gene variant makes an exception. In 1992, an
      immunologically anomalous form of LH was found in a healthy woman, and it was
      subsequently found to be caused by two point mutations leading to two amino acid
      substitutions in the LHbeta subunit. Of the two point mutations, Trp(8)Arg and
      Ile(15)Thr, the first one is mainly responsible for the altered immunoreactivity
      and the latter one introduces an extra glycosylation site into Asn(13) of the
      mutated LHbeta peptide. The frequency of this variant LHbeta allele differs
      widely between ethnic groups, being most common in aboriginal Australians
      (carrier frequency >50%; allelic frequency 28.3%) and totally lacking from Kotas
      of Southern India. Functional differences have been detected when wild-type LH
      and variant LH have been compared. Variant LH possesses increased in vitro
      bioactivity, whereas its half-life in circulation is shorter in comparison to
      wild-type LH. Also the regulation of the variant LHbeta gene differs due to
      additional changes in its promoter sequence. Correlations of occurrence of
      variant LH with various clinical conditions involving LH function suggest that it
      represents a biologically less active form of LH and may be related to borderline
      suppression of gonadal function, including subfertility. In this article, we will
      review the current information about the differences observed in structure and
      functions between the wild-type and variant LH, as well as their possible
      pathophysiological correlations.

PMID- 11230990
TI  - Receptor polymorphisms and diseases.
AB  - The aim of our review is to summarize common genetic variations of some receptors
      associated with clinical consequences, which were not outlined in the previous
      special issue of this journal. Because of the multiple pathomechanisms of
      diseases, a set of genetic variation can play a role in the development of
      pathological conditions. From the data available three articles would merit a
      greater interest. In systemic lupus erythematosus the associations related to
      some polymorphisms of Fc-, tumor necrosis factor (TNF) alpha- and interferon
      receptor may explore new autoimmunological and inflammatorical pathomechanisms.
      In the endocrinology, the androgen receptor repeat polymorphism will exert
      significant aspects in the development of prostate cancer. The pleoitropic
      responsibility of vitamin D3 receptor polymorphism in the pathogenesis of
      immunological disorders (primary biliary cirrhosis, inflammatory bowel disease,
      type 1 diabetes mellitus) and of malignancies (malignant melanoma, breast cancer)
      shed light on the importance of common nuclear receptors. Nevertheless, in the
      future studies a more consistent approach minimizing requirement bias in the
      selection of patients will approve our understanding the role of genetic
      influence on the pathogenesis of diseases.

PMID- 11230991
TI  - Pharmacological characterisation of human 5-HT2 receptor subtypes.
AB  - Prompted by conflicting literature, this study compared the pharmacology of human
      5-hydroxytryptamine2 (5-HT2) receptors expressed in SH-SY5Y cells using a
      fluorometric imaging plate reader (FLIPR) based Ca2+ assay. 5-Hydroxytryptamine
      (5-HT) increased intracellular calcium concentration ([Ca2+]i) at 5-HT2A, 5-HT2B
      and 5-HT2C receptors (pEC(50)=7.73+/-0.03, 8.86+/-0.04 and 7.99+/-0.04,
      respectively) and these responses were inhibited by mesulergine (pKB=7.42+/-0.06,
      8.77+/-0.10 and 9.52+/-0.11). A range of selective agonists and antagonists
      displayed the expected pharmacology at each receptor subtype. Sodium butyrate
      pretreatment increased receptor expression in SH-SY5Y/5-HT2B (15-fold) and SH
      SY5Y/5-HT2C cells (7-fold) and increased agonist potencies and relative
      efficacies. In contrast, sodium butyrate pretreatment of SH-SY5Y/5-HT(2A) cells
      did not affect receptor expression. The present study provides a direct
      comparison of agonist and antagonist pharmacology at 5-HT(2) receptor subtypes in
      a homogenous system and confirms that agonist potency and efficacy varies with
      the level of receptor expression.

PMID- 11230992
TI  - Facilitation of transmitter release in the urinary bladders of neonatal and adult
      rats via alpha1-adrenoceptors.
AB  - Age-dependent changes in the effects of the alpha1-adrenoceptor agonist,
      phenylephrine were investigated on neurally evoked contractile responses and
      basal tone in smooth muscle strips from rat urinary bladder. Phenylephrine
      facilitated the neurogenic contractions in both neonatal and 7-month-old adult
      rats. However, phenylephrine increased the basal tone in adult but not neonatal
      rats. In adult rats, phenylephrine-induced facilitation of neurally evoked
      contractions occurred before and after the block of cholinergic contractions with
      1 microM atropine. In adult rats, the phenylephrine facilitation was reduced at
      stimulation parameters (20 Hz, 80 shocks and maximal voltage) which activated
      muscarinic receptor mediated facilitation of acetylcholine release. The results
      indicate that pre-synaptic alpha1-adrenoceptors facilitate the release of both
      acetylcholine and the non-cholinergic non-adrenergic transmitter. In summary,
      alpha1-adrenoceptor-mediated facilitation is less expressed when muscarinic M1
      receptor mediated facilitation is functioning; pre-junctional alpha1
      adrenoceptors are present in the bladder of both neonatal and adult rats, whereas
      post-junctional alpha1-adrenoceptors are expressed only in older adult rats.

PMID- 11230993
TI  - Negative interaction of dopamine D2 receptor antagonists and GBR 12909 and GBR
      12935 dopamine uptake inhibitors in the nucleus accumbens.
AB  - The objective of this study was to examine the interaction of dopamine D2
      receptor antagonists and dopamine uptake inhibitors on the regulation of
      extracellular dopamine release in the nucleus accumbens of Wistar rats employing
      in vivo microdialysis and in vitro dopamine uptake studies. Application of the D2
      receptor antagonists raclopride (100 microm) or sulpiride (100 microm) alone
      through the microdialysis probe in the nucleus accumbens for 60 min increased the
      extracellular levels of dopamine in the nucleus accumbens to 150% and 200% of
      basal, respectively. Perfusion of the nucleus accumbens for 60 min with the
      dopamine uptake inhibitors, 1-[2-[bis(4-Fluorophenyl)methoxy]ethyl]-4-[3
      phenylpropyl]piperazine dihydrochloride (GBR 12909; 100 microm) or 1-[2
      (Diphenylmethoxy)ethyl]-4-(3-phenylpropyl)-piperazine dihydrochloride (GBR 12935;
      100 microm) alone, increased the extracellular levels of dopamine in the nucleus
      accumbens to 400% and 350% of basal, respectively. Co-perfusion of 100 microM GBR
      12909 or GBR 12935 with either 100 microM sulpiride or raclopride produced a
      significant reduction in the GBR 12909 or GBR 12935 induced increase in the
      extracellular levels of dopamine to basal levels. In vitro, GBR 12909 (1-9 nM)
      dose-dependently inhibited active uptake of [3H]dopamine in homogenates of the
      nucleus accumbens. Addition of 100 microm sulpiride had little effect on GBR
      12909 inhibition of [3H] dopamine uptake, suggesting that dopamine D2 receptor
      antagonists are not blocking the actions of the GBR-type dopamine uptake
      inhibitors at the dopamine transporter. Overall, the data suggest that complex
      interactions occur in vivo between D2 antagonists and GBR-type dopamine uptake
      inhibitors, which negate their effects on elevating the extracellular levels of
      dopamine in the nucleus accumbens.

PMID- 11230994
TI  - Adenosine A1 receptors regulate the response of the hamster circadian clock to
      light.
AB  - Circadian rhythms are synchronized to the environmental light-dark cycle by
      daily, light-induced adjustments in the phase of a biological clock located in
      the suprachiasmatic nucleus. Ambient light alters the phase of the clock via a
      direct, glutamatergic projection from retinal ganglion cells. We investigated the
      hypothesis that adenosine A1 receptors modulate the phase adjusting effect of
      light on the circadian clock. Systemic administration of the selective adenosine
      A1 receptor agonist, N6-cyclohexyladenosine (CHA), significantly (p<0.05)
      attenuated light-induced phase delays and advances of the circadian activity
      rhythm. Selective agonists for the adenosine A2A and adenosine A3 receptors were
      without effect. The inhibitory effect of CHA on light-induced phase advances was
      dose-dependent (0.025-1.0 mg/kg, ED(50)=0.3 mg/kg), and this effect was blocked
      in a dose-dependent (0.005-1.0 mg/kg) manner by the adenosine A1 receptor
      antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Injection of CHA (10
      microM) into the region of the suprachiasmatic nucleus significantly attenuated
      light-induced phase advances, and this effect was also blocked by DPCPX (100
      microM). The results suggest that adenosine A1 receptors located in the region of
      the suprachiasmatic nucleus regulate the response of the circadian clock to the
      phase-adjusting effects of light.

PMID- 11230995
TI  - Role of adenosine and glycogen in ischemic preconditioning of rat hearts.
AB  - We tested whether ischemic preconditioning of the rat heart is mediated by
      reduced glycogenolysis during ischemia, an event triggered by adenosine A1
      receptor activation. Rat hearts (n=40) were studied with [31P] and [13C] nuclear
      magnetic resonance (NMR) spectroscopy, using the Langendorff perfusion technique
      (5.5 mM [1-13C]glucose, 10 U/l insulin). In parallel experiments, hearts (n=43)
      were freeze-clamped at different time-points throughout the protocol. They were
      subjected to either ischemic preconditioning (PC), PC in the presence of 50
      microM adenosine receptor antagonist, 8-(p-sulfophenyl)-theophylline (SPT), or
      intermittent infusion of 0.25 microM adenosine A1 receptor agonist, 2-chloro-N6
      cyclopentyladenosine (CCPA). After 30 min ischemia and reperfusion, recovery of
      heart ratexpressure product was improved in hearts treated with preconditioning
      (33+/-13%) or CCPA (58+/-14%) compared with the SPT and ischemic control (IC)
      groups, which both failed to recover (P<0.05). CCPA administration induced a 58%
      increase in pre-ischemic [13C]glycogen (P<0.05 vs. all groups). In the PC and SPT
      groups, [13C]glycogen decreased by 25 and 47%, respectively (P<0.05) due to the
      short bouts of ischemia, resulting in lower pre-ischemic glycogen compared to
      ischemic control and CCPA hearts (P<0.05). The rate of [13C]glycogen utilization
      during the first 15 min of ischemia (in micromol/min g wwt) was not statistically
      different between IC (0.42+/-0.03), PC (0.30+/-0.04), and CCPA (0.38+/-0.05)
      hearts, but was reduced in SPT hearts (0.24+/-0.05; P<0.05). Total glycogen
      depletion during 30-min ischemia was reduced in PC hearts (0.61 mg/g wwt)
      compared to IC (1.84 mg/g wwt) and CCPA (1.75 mg/g wwt) hearts; SPT did not block
      reduced glycogenolysis during ischemia in PC hearts (0.77 mg/g wwt vs. IC). This
      study adds further strong evidence that in rat hearts, adenosine is involved in
      ischemic preconditioning. However, protection is unrelated to pre-ischemic
      glycogen levels and glycogenolysis during ischemia.

PMID- 11230996
TI  - Recovery of microvascular responses during streptozotocin-induced diabetes.
AB  - Microvascular reactivity of cannulated and pressurised rat cremaster arterioles
      was studied during the progress of diabetes using mechanical (intraluminal
      pressure) and chemical (acetylcholine, sodium nitroprusside) stimulation.
      Microvessels were studied in controls and at 2, 4 and 8 weeks following induction
      of diabetes by streptozotocin. Mechanical responses were stable at the test
      pressure (70 mmHg) used for pharmacological investigations during the period of
      diabetes. Acetylcholine application could induce maximal dilatation in control
      vessels and in vessels exposed to 8 weeks of diabetes. However, acetylcholine
      administration failed to generate maximal dilatation at 2 and 4 weeks of
      diabetes. During the period of diabetes, loss of nitric oxide (NO) pathway
      effectiveness was revealed by diminished response to sodium nitroprusside and by
      reduced capacity of Nomega-nitro-L-arginine methyl ester (L-NAME) to decrease
      resting diameter and acetylcholine-evoked dilatation. L-NAME and indomethacin
      application revealed a significant non-NO, non-prostaglandin contribution to the
      acetylcholine response at 4 and 8 weeks of diabetes. Recovery of responsiveness
      to acetylcholine and stabilisation of resting vessel diameter during diabetes
      may, in part, be due to increasing effectiveness of non-NO, non-prostaglandin
      pathways.

PMID- 11230997
TI  - Cardioprotective effects of zofenopril, a new angiotensin-converting enzyme
      inhibitor, on doxorubicin-induced cardiotoxicity in the rat.
AB  - We have studied the effect of zofenopril, a new angiotensin-converting enzyme
      inhibitor in preventing cardiac injury induced by chronic doxorubicin treatment
      in rats. Cardiac function was assessed by measuring changes in electrocardiogram
      (ECG) tracings, haemodynamics and cardiac responses in vivo to isoprenaline, 4
      weeks after suspension of doxorubicin treatment, in vehicle-treated rats and in
      animals receiving zofenopril (15 mg/kg/os/day) alone, doxorubicin (1.5 mg/kg i.v.
      once a week for 5 weeks) or zofenopril+doxorubicin treatment. Doxorubicin induced
      a significant lengthening of the QalphaT interval, which was completely prevented
      by zofenopril treatment. The cardiac positive inotropic effect induced by i.v.
      isoprenaline was selectively depressed by doxorubicin (no changes in chronotropic
      responses) and this adverse effect of doxorubicin was also prevented in
      zofenopril+doxorubicin pretreated rats. Doxorubicin induced a significant
      increase in relative heart weight, which was likewise prevented in
      zofenopril+doxorubicin treated rats. In separate experiments, zofenopril did not
      interfere with the antitumor activity of doxorubicin (inhibition of tumor growth
      in nude mice xenografted with A2780 human tumor line). In conclusion, the oral
      administration of zofenopril is able to significantly ameliorate, up to 4 weeks
      after the end of doxorubicin administration, doxorubicin-induced cardiotoxicity
      without affecting the antitumor activity of this anthracycline.

PMID- 11230998
TI  - Effects of food intake and oxidative stress on intestinal lesions caused by
      meloxicam and piroxicam in rats.
AB  - Large intestinal ulcers, bleeding and perforation are occasionally due to non
      steroidal anti-inflammatory drugs (NSAID). In addition to suppression of
      prostaglandins synthesis, a number of factors have been implicated, including
      enterohepatic recirculation, food intake and vascular injury with oxygen free
      radical generation. The present study aimed to determine the effect of food
      intake and the role of oxidative stress in the pathogenesis of intestinal injury
      induced by oral administration of meloxicam (preferential cyclooxygenase-2
      inhibitor) vs. piroxicam (preferential cyclooxygenase-1 inhibitor). Therefore,
      the activity of oxidative stress-related enzymes such as myeloperoxidase,
      xanthine oxidase and superoxide dismutase, as well as levels of lipid peroxides
      and glutathione homeostasis were studied in an experimental model using re-fed
      rats. The animals treated with piroxicam (10-20 mg/kg) had a dose-dependent
      increase in the severity of intestinal lesions, but only the highest dose of
      meloxicam (15 mg/kg) caused macroscopic damage. The severity of piroxicam and
      meloxicam-induced damage was correlated with a significant increase of xantine
      oxidase activity and a decrease of superoxide dismutase activity and glutathione
      levels (P<0.05 and P<0.001 vs. control). In contrast, there was no significant
      neutrophil infiltration of the intestine after dosing. Our results support the
      hypothesis that oxygen free radicals, probably derived via the action of xantine
      oxidase, the decrease in superoxide dismutase activity, and depletion of mucosal
      glutathione contribute to the pathogenesis of meloxicam and piroxicam-induced
      intestinal ulceration in re-fed rats.

PMID- 11230999
TI  - Role of leptin in ulcer healing.
AB  - Leptin was shown to exhibit similar to cholecystokinin (CCK) cytoprotective
      activity against acute gastric lesions, but its role in ulcer healing has not
      been examined. The aims of this study were: (1) to compare the effects of
      exogenous leptin to those of CCK on the course of healing of chronic gastric
      ulcers; (2) to study the gene and protein expression of leptin at the ulcer
      margin during ulcer healing; and (3) to assess the effects of leptin
      administration on the mucosal gene expression of main growth factor such as
      transforming growth factor alpha (TGFalpha). Gastric ulcers were produced in rats
      by the acetic acid method. Rats with ulcers were divided in following treatment
      groups: (1) vehicle; (2) leptin (10 microg/kg i.p.); (3) CCK (10 microg/kg s.c.);
      and (4) leptin or CCK with or without tyrphostin A46 (200 microg/kg i.p.), an
      inhibitor of epidermal growth factor (EGF)-receptor tyrosine kinase or NG-nitro-L
      arginine (20 mg/kg i.g.), a blocker of nitric oxide synthase. Animals were
      euthanized 9 days after ulcer induction. The area of gastric ulcers and the
      gastric blood flow at the ulcer area were determined. In addition, mucosal biopsy
      samples were taken from the ulcer area for histological evaluation as well as for
      the determination of mRNA and protein expression for leptin and constitutive
      nitric oxide synthase (cNOS) and inducibile nitric oxide synthase (iNOS) by
      reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blot,
      respectively. In addition, the gene expression for TGFalpha was analyzed by RT
      PCR. Both leptin and CCK reduced significantly the ulcer area as compared to
      vehicle-treated group by approximately 50%. The treatment with tyrphostin or N(G)
      nitro-L-arginine reversed in part the acceleration of ulcer healing by leptin and
      CCK. The expression of leptin mRNA and protein was significantly increased at the
      ulcer edge. The leptin-induced acceleration of ulcer healing was associated with
      increased expression of transcripts for TGFalpha as well as increased mRNA and
      protein expression for cNOS and iNOS at the ulcer margin. We conclude that leptin
      accelerates ulcer healing by mechanisms involving the up-regulation of TGFalpha
      and increased production of nitric oxide due to up-regulation of cNOS and iNOS in
      the ulcer area.

PMID- 11231000
TI  - The selective adenosine A1 receptor antagonist KW-3902 prevents radiocontrast
      media-induced nephropathy in rats with chronic nitric oxide deficiency.
AB  - Several studies have recently suggested a principal role of adenosine in the
      pathogenesis of radiocontrast media-induced nephropathy. In the present
      experiments, we therefore investigated the renal protective effects of 8
      (noradamantan-3-yl)-1,3-dipropylxanthine (KW-3902), a potent and selective
      adenosine A1 receptor antagonist, on radiocontrast media-induced nephropathy in
      the model of the N-pi-nitro-L-arginine methyl ester (L-NAME) hypertensive,
      chronic nitric oxide (NO)-depleted rat. Chronic NO depletion was induced by
      pretreatment with L-NAME, 50 mg/ml, added to drinking water for 8 weeks.
      Clearance experiments were performed in anesthetized rats and glomerular
      filtration rate was assessed prior to and following the application of high
      osmolar radiocontrast media (sodium diatrizoate, 3 ml/kg, i.v.) or an equivalent
      volume of isoosmolar mannitol to examine the role of hyperosmolarity in
      radiocontrast media-induced nephropathy. Subgroups received KW-3902 (0.1 mg/kg,
      i.v.), 20 min prior to radiocontrast media administration. Age-matched, untreated
      rats served as controls. Radiocontrast media application induced a significant
      decline in glomerular filtration rate in L-NAME hypertensive animals, whereas no
      effects were observed in control rats. KW-3902 fully prevented the drop in
      glomerular filtration rate in response to radiocontrast media in L-NAME
      hypertensive rats. No renal hemodynamic alterations were observed in mannitol
      infused animals. The present experiments demonstrate that the decrease in
      glomerular filtration rate following radiocontrast media occurred independently
      of the osmotic load, and that KW-3902 effectively prevented the radiocontrast
      media-induced deterioration in renal function. KW-3902 may be especially
      beneficial in patients at high risk for developing acute renal failure following
      radiocontrast media application or in patients in which extracellular fluid
      volume expansion is limited by clinical conditions such as congestive heart
      failure.

PMID- 11231001
TI  - Mast cells can revert dexamethasone-mediated down-regulation of stem cell factor.
AB  - Mast cell hyperplasia can be causally related with chronic inflammation and liver
      fibrosis. Their survival and proliferation is dependent upon locally produced
      growth factors, the major one being the stem cell factor (SCF). Glucocorticoids
      can decrease mastocytosis, down-regulating the mast cell production of pro
      inflammatory factors or inhibiting the expression of SCF in stroma. We compared
      dexamethasone effect on SCF expression in co-cultures of mast cells with NIH/3T3
      fibroblasts or with primary cultures of activated hepatic stellate cells.
      Dexamethasone abrogated the NIH/3T3 stroma capacity to sustain mast cell
      proliferation, but not of hepatic stellate cells, at the post-transcriptional
      level. Mast cells reverted completely dexamethasone effect on hepatic stellate
      cells, increasing their SCF synthesis and transport. In both models,
      dexamethasone inhibited the mast cell spreading on the stroma, which was thus not
      required for mast cell survival and proliferation. Liver pathologies associated
      with mast cell hyperplasia are not expected to be sensitive to glucocorticoid
      treatments.

PMID- 11231002
TI  - A potential role of chlorophylls b and c in assembly of light-harvesting
      complexes.
AB  - Chlorophyll (Chl)-containing light-harvesting complexes (LHCs) in chloroplasts of
      plant and algal cells usually include an oxidized Chl (Chl b or c) in addition to
      Chl a. Oxidation of peripheral groups on the tetrapyrrole structure increases the
      Lewis acid strength of the central Mg atom. We propose that the resulting
      stronger coordination bonds between oxidized Chls and ligands in LHC apoproteins
      (LHCPs) stabilize the initial intermediates and thus promote assembly of LHCs
      within the chloroplast envelope.

PMID- 11231003
TI  - Aquaporin 3, a glycerol and water transporter, is regulated by p73 of the p53
      family.
AB  - p73, a member of the p53 family, has been shown to exhibit similar biochemical
      activities to that of p53. However, in contrast to p53, p73 is rarely mutated in
      human tumors and p73 mutant mice develop neurological, pheromonal, and
      inflammatory defects, but not spontaneous tumors. Furthermore, p73 mutant mice
      are deficient in the physiological control of cerebral spinal fluid. To determine
      what mediates these p73 activities, cDNA subtraction assay was performed to
      identify cellular genes that are regulated by p73. We found that aquaporin 3
      (AQP3), a glycerol and water transporter, is regulated by p73. In addition, we
      identified a potential p53 response element in the promoter of the AQP3 gene,
      which is responsive to p73. This suggests that AQP3 may mediate the activity of
      p73 in maintaining cerebral spinal fluid dynamics.

PMID- 11231004
TI  - NMR structure of the haem core of a novel tetrahaem cytochrome isolated from
      Shewanella frigidimarina: identification of the haem-specific axial ligands and
      order of oxidation.
AB  - The tetrahaem cytochrome isolated during anaerobic growth of Shewanella
      frigidimarina NCIMB400 is a small protein (86 residues) involved in electron
      transfer to Fe(III), which can be used as a terminal respiratory oxidant by this
      bacterium. A 3D solution structure model of the reduced form of the cytochrome
      has been determined using NMR data in order to determine the relative orientation
      of the haems. The haem core architecture of S. frigidimarina tetrahaem cytochrome
      differs from that found in all small tetrahaem cytochromes c(3) so far isolated
      from strict anaerobes, but has some similarity to the N-terminal cytochrome
      domain of flavocytochrome c(3) isolated from the same bacterium. NMR signals
      obtained for the four haems of S. frigidimarina tetrahaem cytochrome at all
      stages of oxidation were cross-assigned to the solution structure using the
      complete network of chemical exchange connectivities. Thus, the order in which
      each haem in the structure becomes oxidised was determined.

PMID- 11231006
TI  - Redox-regulated chaperone function and conformational changes of Escherichia coli
      Hsp33.
AB  - We have studied the chaperone activity and conformation of Escherichia coli heat
      shock protein (Hsp)33, whose activity is known to be switched on by oxidative
      conditions. While oxidized Hsp33 completely prevents the heat-induced aggregation
      of zeta-crystallin at 42 degrees C at a ratio of 1:1 (w/w), the reduced form
      exhibits only a marginal effect on the aggregation. Far UV-circular dichroism
      (CD) spectra show that reduced Hsp33 contains a significant alpha-helical
      component. Oxidation results in significant changes in the far UV-CD spectrum.
      Near UV-CD spectra show changes in tertiary structural packing upon oxidation.
      Polarity-sensitive fluorescent probes report enhanced hydrophobic surfaces in the
      oxidized Hsp33. Our studies show that the oxidative activation of the chaperone
      function of Hsp33 involves observable conformational changes accompanying
      increased exposure of hydrophobic pockets.

PMID- 11231005
TI  - Two histidine residues are essential for catalysis by lecithin retinol acyl
      transferase.
AB  - Lecithin retinol acyl transferase (LRAT) is a novel membrane bound enzyme that
      catalyzes the formation of retinyl esters from vitamin A and lecithin. The enzyme
      is both essential for vision and for the general mobilization of vitamin A. The
      sequence of LRAT defines it as a novel enzyme unrelated to any other protein of
      known function. LRAT possesses a catalytically essential active site cysteine
      residue. The enzyme also contains six histidine residues. It is shown here that
      two of these residues (H57 and H163) are essential for catalysis. A mechanistic
      hypothesis is presented to account for these observations.

PMID- 11231007
TI  - A suicide-substrate mechanism for hydrolysis of beta-lactams by an anti-idiotypic
      catalytic antibody.
AB  - The catalytic mechanism of an anti-idiotypic antibody, 9G4H9, displaying a beta
      lactamase activity was investigated. Kinetics experiments suggest that some
      penicillinic derivatives behave both as substrates and inactivators. Biochemical
      and immunological experiments strongly indicate that ampicillin may be regarded
      as a suicide substrate for hydrolysis by 9G4H9. The anti-idiotypic network
      appears as a way to create enzyme mimics with modified catalytic activities.

PMID- 11231008
TI  - Protein aggregation as bacterial inclusion bodies is reversible.
AB  - Inclusion bodies are refractile, intracellular protein aggregates usually
      observed in bacteria upon targeted gene overexpression. Since their occurrence
      has a major economical impact in protein production bio-processes, in vitro
      refolding strategies are under continuous exploration. In this work, we prove
      spontaneous in vivo release of both beta-galactosidase and P22 tailspike
      polypeptides from inclusion bodies resulting in their almost complete
      disintegration and in the concomitant appearance of soluble, properly folded
      native proteins with full biological activity. Since, in particular, the
      tailspike protein exhibits an unusually slow and complex folding pathway
      involving deep interdigitation of beta-sheet structures, its in vivo refolding
      indicates that bacterial inclusion body proteins are not collapsed into an
      irreversible unfolded state. Then, inclusion bodies can be observed as transient
      deposits of folding-prone polypeptides, resulting from an unbalanced equilibrium
      between in vivo protein precipitation and refolding that can be actively
      displaced by arresting protein synthesis. The observation that the formation of
      big inclusion bodies is reversible in vivo can be also relevant in the context of
      amyloid diseases, in which deposition of important amounts of aggregated protein
      initiates the pathogenic process.

PMID- 11231009
TI  - Identification of mouse Jun dimerization protein 2 as a novel repressor of ATF-2.
AB  - A mouse cDNA that encodes a DNA-binding protein was identified by yeast two
      hybrid screening, using activating transcription factor-2 (ATF-2) as the bait.
      The protein contained a bZIP (basic amino acid-leucine zipper region) domain and
      its amino acid sequence was almost identical to that of rat Jun dimerization
      protein 2 (JDP2). Mouse JDP2 interacted with ATF-2 both in vitro and in vivo via
      its bZIP domain. It was encoded by a single gene and various transcripts were
      expressed in all tested tissues of adult mice, as well as in embryos, albeit at
      different levels in various tissues. Furthermore, mouse JDP2 bound to the cAMP
      response element (CRE) as a homodimer or as a heterodimer with ATF-2, and
      repressed CRE-dependent transcription that was mediated by ATF-2. JDP2 was
      identified as a novel repressor protein that affects ATF-2-mediated
      transcription.

PMID- 11231010
TI  - Enzymatic synthesis of a novel trehalose derivative, 3,3'-diketotrehalose, and
      its potential application as the trehalase enzyme inhibitor.
AB  - We reported the preparation of a novel trehalose derivative based on enzymatic
      oxidation of trehalose by water-soluble glucose-3-dehydrogenase (G3DH) from
      marine bacterium Halomonas sp. alpha-15 cells. The product of G3DH enzymatic
      conversion was 3,3'-diketotrehalose (3,3'dkT), a novel trehalose derivative of
      which both third hydroxy groups of glucopyranosides were oxidized. 3,3'dkT was
      revealed to show an inhibitory effect toward pig-kidney and Bombyx mori
      trehalases. The IC(50) values of 3,3'dkT were 0.8 and 2.5 mM and K(i) values were
      0.2 and 0.6 mM for pig-kidney and for B. mori trehalases, respectively. In
      addition, 3,3'dkT did not show any inhibitory effect on both maltase and
      mannosidase activities. Therefore, 3,3'dkT was a specific inhibitor of
      trehalases.

PMID- 11231012
TI  - Inhibition of 15-lipoxygenase leads to delayed organelle degradation in the
      reticulocyte.
AB  - Mammalian cells are characterized by an endomembrane system. Nevertheless, some
      cells lose these membranes during their terminal differentiation, e.g. red blood
      cells and lens fiber cells of the eye. 15-Lipoxygenase is believed to be critical
      for this membrane degradation. Here we use cultivated rabbit reticulocytes in the
      presence or absence of a lipoxygenase inhibitor to provide further evidence for
      the importance of 15-lipoxygenase for the in vivo degradation of mitochondria. We
      find that inhibitor treatment retarded mitochondrial degradation, as shown by
      persistence of marker proteins and by direct visualization of mitochondria by
      electron microscopy.

PMID- 11231011
TI  - Calpain-mediated degradation of p35 to p25 in postmortem human and rat brains.
AB  - Tau in Alzheimer neurofibrillary tangles has been shown to be hyperphosphorylated
      and CDK5, GSK3, MAP kinase and SAP kinases are the candidate kinases for the
      phosphorylation of tau. Recently, it was reported that the conversion of p35, the
      activator of CDK5, to p25 was upregulated in Alzheimer's disease (AD) brains, and
      that p35 is cleaved to yield p25 by calpain. Here we show that p35 is rapidly
      cleaved to p25 in rat and human brains within a short postmortem delay and that
      the conversion of p35 to p25 is partially dependent on calpain activity.
      Immunoblot analysis of brains prepared from patients with AD or age-matched
      control individuals with a short postmortem delay revealed no specific increase
      in the levels of p25 in AD brains, whereas the levels of active form of calpain
      were increased in AD brains compared to the those in controls. These observations
      suggest that the conversion of p35 to p25 is a postmortem degradation event and
      may not be upregulated in AD brains.

PMID- 11231013
TI  - Fatty acids bind to the fungal elicitor cryptogein and compete with sterols.
AB  - Cryptogein is a proteinaceous elicitor of plant defense reactions which also
      exhibits sterol carrier properties. In this study, we report that this protein
      binds fatty acids. The stoichiometry of the fatty acid-cryptogein complex is 1:1.
      Linoleic acid and dehydroergosterol compete for the same site, but elicitin
      affinity is 27 times lower for fatty acid than for sterol. We show that C7 to C12
      saturated and C16 to C22 unsaturated fatty acids are the best ligands. The
      presence of double bonds markedly increases the affinity of cryptogein for fatty
      acids. A comparison between elicitins and known lipid transfer proteins is
      discussed.

PMID- 11231014
TI  - Human fibulin-4: analysis of its biosynthetic processing and mRNA expression in
      normal and tumour tissues.
AB  - Here, we report the identification of a human orthologue of fibulin-4, along with
      analysis of its biosynthetic processing and mRNA expression levels in normal and
      tumour tissues. Comparative sequence analysis of fibulin-4 cDNAs revealed
      apparent polymorphisms in the signal sequence that could account for previously
      reported inefficient secretion in fibulin-4 transfectants. In vitro translation
      of fibulin-4 mRNA revealed the presence of full-length and truncated
      polypeptides, the latter apparently generated from an alternative translation
      initiation site. Since this polypeptide failed to incorporate into endoplasmic
      reticulum membrane preparations, it was concluded that it lacked a signal
      sequence and thus could represent an intracellular form of fibulin-4. Using
      fluorescence in situ hybridisation analysis, the human fibulin-4 gene was
      localised to chromosome 11q13, this region being syntenic to portions of mouse
      chromosomes 7 and 19. Considering the fact that translocations, amplifications
      and other rearrangements of the 11q13 region are associated with a variety of
      human cancers, the expression of human fibulin-4 was evaluated in a series of
      colon tumours. Reverse transcription-polymerase chain reaction analysis of RNA
      from paired human colon tumour and adjacent normal tissue biopsies showed that a
      significant proportion of tumours had approximately 2-7-fold increases in the
      level of fibulin-4 mRNA expression. Taken together, results reported here suggest
      that an intracellular form of fibulin-4 protein may exist and that dysregulated
      expression of the fibulin-4 gene is associated with human colon tumourigenesis.

PMID- 11231015
TI  - Intermolecular interactions between the SH3 domain and the proline-rich TH region
      of Bruton's tyrosine kinase.
AB  - The SH3 domain of Bruton's tyrosine kinase (Btk) is preceded by the Tec homology
      (TH) region containing proline-rich sequences. We have studied a protein fragment
      containing both the Btk SH3 domain and the proline-rich sequences of the TH
      region (PRR-SH3). Intermolecular NMR cross-relaxation measurements, gel
      permeation chromatography profiles, titrations with proline-rich peptides, and
      (15)N NMR relaxation measurements are all consistent with a monomer-dimer
      equilibrium with a dissociation constant on the order of 60 microM. The
      intermolecular interactions do, at least in part, involve proline-rich sequences
      in the TH region. This behavior of Btk PRR-SH3 may have implications for the
      functional action of Btk.

PMID- 11231016
TI  - Location of a ligand recognition site of FMRFamide-gated Na(+) channels.
AB  - The second FMRFamide-gated Na(+) channel (HtFaNaC), from Helisoma trivolvis, has
      been cloned. HtFaNaC has some different pharmacological properties to HaFaNaC,
      from Helix aspersa, which has enabled a rational approach to be made to start to
      identify the FMRFamide recognition site. Several chimeras were made by switching
      sections between the channels. The differences in sensitivity to FMRFamide, and
      amiloride, were assessed after expression in Xenopus oocytes. The data suggest
      that a recognition site for FMRFamide, and the potentiating action of amiloride,
      resides in a sequence of about 120 amino acids in the extracellular loop proximal
      to the first transmembrane segment.

PMID- 11231017
TI  - Schizosaccharomyces pombe och1(+) encodes alpha-1,6-mannosyltransferase that is
      involved in outer chain elongation of N-linked oligosaccharides.
AB  - The fission yeast Schizosaccharomyces pombe attaches an outer chain containing
      mannose and galactose to the N-linked oligosaccharides on many of its
      glycoproteins. We identified an S. pombe och1 mutant that did not synthesize the
      outer chains on acid phosphatase. The S. pombe och1(+) gene was a functional
      homolog of Saccharomyces cerevisiae OCH1, and its gene product (SpOch1p)
      incorporated alpha-1,6-linked mannose into pyridylaminated Man(9)GlcNAc(2),
      indicating that och1(+) encodes an alpha-1,6-mannosyltransferase. Our results
      indicate that SpOch1p is a key enzyme of outer chain elongation. The substrate
      specificity of SpOch1p was different from that of S. cerevisiae OCH1 gene product
      (ScOch1p), suggesting that SpOch1p may have a wider substrate specificity than
      that of ScOch1p.

PMID- 11231018
TI  - Evidence for the involvement of the GTS1 gene product in the regulation of
      biological rhythms in the continuous culture of the yeast Saccharomyces
      cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae, ultradian oscillations of energy
      metabolism have been observed in continuous cultures. Here, we found that the
      level of the GTS1 gene product oscillated in concert with the ultradian rhythm of
      energy metabolism. When GTS1 was inactivated by gene disruption, the metabolic
      oscillation was affected severely, mostly disappearing within a day, in the
      absence of synchronized stress-response oscillations throughout the continuous
      culture. The disappearance of biological rhythms in the GTS1-deleted mutant was
      substantially rescued by transformation with chimera plasmids carrying GTS1 under
      the control of GTS1's own promoter. On the other hand, this disappearance was not
      rescued by constitutive expression of GTS1 under the control of the triose
      phosphate isomerase promoter.

PMID- 11231019
TI  - Ser(1901) of alpha(1C) subunit is required for the PKA-mediated enhancement of L
      type Ca(2+) channel currents but not for the negative shift of activation.
AB  - Cardiac L-type Ca(2+) channel is facilitated by protein kinase A (PKA)-mediated
      phosphorylation. Here, we investigated the role of Ser(1901), a putative
      phosphorylation site in the carboxy-terminal of rat brain type-II alpha(1C)
      subunit (rbCII), in the PKA-mediated regulation. Forskolin (3 microM) enhanced
      Ca(2+) channel currents (I(Ca)) and shifted the activation curve to negative
      voltages, which were abolished by protein kinase inhibitor. Replacement of
      Ser(1901) of rbCII by Ala abolished the enhancement of I(Ca) by forskolin but not
      the shift of the activation curve. These results indicate that Ser(1901) is
      required for the PKA-mediated enhancement of I(Ca), and that the voltage
      dependence of the activation of I(Ca) appears to be modulated via another PKA
      phosphorylation site.

PMID- 11231021
TI  - Salivary histatin 5 is a potent competitive inhibitor of the cysteine proteinase
      clostripain.
AB  - Histatin 5 is a low molecular weight salivary protein which is known to exhibit
      inhibitory activity against several proteinases, including the cysteine
      proteinases gingipains. The purpose of this study was to characterize the effect
      of salivary histatin on the proteolytic activity of the cysteine proteinase
      clostripain derived from the pathogen Clostridium histolyticum. Using a synthetic
      nitroanilide substrate, we studied in detail the inhibition of clostripain by
      histatin 5 and compared the effect of this peptide to that of leupeptin, a known
      competitive inhibitor of clostripain. It was found that the concentration of
      histatin 5 required to inhibit 50% of clostripain activity was 23.6+/-1.6 nM.
      Kinetic analysis revealed that histatin 5 is a competitive inhibitor of
      clostripain with an inhibition constant (K(i)) of 10 nM. The K(i) for the
      inhibition of clostripain activity against nitroanilide substrate by leupeptin
      was found to be 60 nM, significantly higher than that of histatin 5. Thus,
      histatin 5 inhibits clostripain more effectively than leupeptin and other
      cysteine protease inhibitors studied here. No significant proteolysis of histatin
      5 was observed when histatin 5 was incubated at physiologic concentrations with
      clostripain. The potent inhibition of clostripain by histatin 5 points towards
      the possibility that this protein may prevent establishment of clostridial
      infections and therefore may have significant potential for the treatment of
      diseases associated with this enzyme.

PMID- 11231020
TI  - Mitochondrial Hsp78, a member of the Clp/Hsp100 family in Saccharomyces
      cerevisiae, cooperates with Hsp70 in protein refolding.
AB  - The molecular chaperone protein Hsp78, a member of the Clp/Hsp100 family
      localized in the mitochondria of Saccharomyces cerevisiae, is required for
      maintenance of mitochondrial functions under heat stress. To characterize the
      biochemical mechanisms of Hsp78 function, Hsp78 was purified to homogeneity and
      its role in the reactivation of chemically and heat-denatured substrate protein
      was analyzed in vitro. Hsp78 alone was not able to mediate reactivation of
      firefly luciferase. Rather, efficient refolding was dependent on the simultaneous
      presence of Hsp78 and the mitochondrial Hsp70 machinery, composed of
      Ssc1p/Mdj1p/Mge1p. Bacterial DnaK/DnaJ/GrpE, which cooperates with the Hsp78
      homolog, ClpB in Escherichia coli, could not substitute for the mitochondrial
      Hsp70 system. However, efficient Hsp78-dependent refolding of luciferase was
      observed if DnaK was replaced by Ssc1p in these experiments, suggesting a
      specific functional interaction of both chaperone proteins. These findings
      establish the cooperation of Hsp78 with the Hsp70 machinery in the refolding of
      heat-inactivated proteins and demonstrate a conserved mode of action of ClpB
      homologs.

PMID- 11231022
TI  - CCK2 (CCK(B)/gastrin) receptor mediates rapid protein kinase D (PKD) activation
      through a protein kinase C-dependent pathway.
AB  - Addition of gastrin or cholecystokinin octapeptide (CCK-8) to cultures of Rat-1
      cells stably transfected with the CCK2 (CCK(B)/gastrin) receptor induced protein
      kinase D (PKD) activation that was detectable within 1 min and reached a maximum
      ( approximately 10-fold) after 2.5 min of hormonal stimulation. Half-maximal PKD
      activation for both CCK-8 and gastrin was achieved at 10 nM. Treatment with
      various concentrations of the selective PKC inhibitors Ro 31-8220 or GF-I
      potently blocked PKD activation induced by subsequent addition of CCK-8 in a
      concentration-dependent fashion. Our results indicate that PKC-dependent PKD
      activation is a novel early event in the action of gastrin and CCK-8 via CCK2
      receptors.

PMID- 11231024
TI  - The N-terminal domain of the Caulobacter crescentus CgtA protein does not
      function as a guanine nucleotide exchange factor.
AB  - The Caulobacter crescentus GTP binding protein CgtA is a member of the Obg/GTP1
      subfamily of monomeric GTP binding proteins. In vitro, CgtA displays moderate
      affinity for both GDP and GTP, and rapid exchange rate constants for either
      nucleotide. One possible explanation for the observed rapid guanine nucleotide
      exchange rates is that CgtA is a bimodal protein with a C-terminal GTP binding
      domain and an N-terminal guanine nucleotide exchange factor (GEF) domain. In this
      study we demonstrate that although the N-terminus of CgtA is required for
      function in vivo, this domain plays no significant role in the guanine nucleotide
      binding, exchange or GTPase activity.

PMID- 11231025
TI  - Charcot-Marie-Tooth disease (CMT): distinctive phenotypic and genotypic features
      in CMT type 2.
AB  - Charcot-Marie-Tooth disease (CMT), or hereditary motor and sensory neuropathy
      (HMSN), includes two main subtypes of CMT1/HMSN I (demyelinating), and CMT2/HMSN
      II (axonal). Further heterogeneity has been demonstrated by genetic molecular
      studies, with at least four responsible genes for CMT1. As for CMT2, a mutation
      in the neurofilament-light (NF-L) gene has been identified in a single family,
      and other CMT2 loci have been mapped. We propose a clinical classification of the
      CMT2 phenotypes, and review the features of the identified CMT2 genotypes. The
      following main subtypes of CMT2 are considered in the phenotype classification:
      classical CMT2, the variants of CMT2 showing atypical features that may represent
      either variance in the classical CMT2 phenotype or separate entities; CMT2 plus,
      i.e. complex forms with involvement of additional neural structures. The
      recognized CMT2 genotypes include: CMT2A (mapped to chromosome 1p35-36); CMT2B
      (3q13-22); CMT2C (with vocal cord paresis); CMT2D (7p14); CMT2E, related to a
      mutation in the NF-L gene on chromosome 8p21; proximal CMT2, or HMSN P (3q13.1);
      CMT2 with MPZ mutations; autosomal recessive CMT2 (1q21.2-q21.3); agenesis of the
      corpus callosum with sensorimotor neuronopathy (15q13-q15); CMT2 X-linked with
      deafness and mental retardation (Xq24-q26). The identified genotypes may
      correspond to previously described clinical subtypes of CMT2. In particular,
      classical CMT2 presents in association with NF-L gene mutation, in the only CMT2
      family with known gene mutation, and in CMT2A patients. However, the features of
      classical CMT2 have been paradoxically reported also in families with MPZ
      mutation, and conversely several CMT2 families are not linked to the known CMT2
      loci. Further cloning of the CMT2 genes will ultimately shed light on the
      pathogenic mechanism(s) implicated in the process of axonal degeneration, shared
      by the different CMT2 genotypes.

PMID- 11231026
TI  - Progressive amyotrophy as a late complication of myelopathy.
AB  - A delayed syndrome of progressive weakness has been described in survivors of
      paralytic poliomyelitis - "Post-Polio Muscular Atrophy (PPMA)". One proposed
      etiology is a drop-out of motor neurons due to increased metabolic demands of an
      enlarged motor unit territory. We report a patient with slowly progressive lower
      extremity weakness 20 years after recovery from an episode of myelopathy
      involving the lower lumbar and sacral segments of the spinal cord. Delayed
      progressive amyotrophy may complicate any significant injury to anterior horn
      cells.

PMID- 11231027
TI  - Phenotypic variation in a large Japanese family with Miyoshi myopathy with
      nonsense mutation in exon 19 of dysferlin gene.
AB  - Miyoshi myopathy, an autosomal recessive muscular dystrophy involving distal
      muscles, is caused by dysferlin mutations. We present clinical and genetic
      studies of two men and six women, aged 25-83 years, from a Japanese family with
      consanguineous marriages. Onset was between ages 17 and 59 years. Six of the
      patients had muscle involvement typical of Miyoshi myopathy, one initially had
      severe proximal muscle involvement, and one had scapuloperoneal-type muscle
      involvement. Three patients showed steppage gait. Genetic linkage analysis
      identified a maximum lod score of 3.34 (&theta;=0.00) at marker D2S292 in 2p13.
      Analysis of dysferlin revealed the mutation G2090T (Glu573Stop) in exon 19 in all
      affected patients. This is the largest Japanese family with Miyoshi myopathy
      showing intrafamilial phenotypic variation and sharing a common mutation in
      dysferlin.

PMID- 11231028
TI  - Association of alpha-2-macroglobulin deletion polymorphism with sporadic
      Alzheimer's disease in Koreans.
AB  - Alpha-2-macroglobulin (A2M) deletion polymorphism was recently reported to be
      associated with Alzheimer's disease (AD) in a way comparable to apolipoprotein E
      (APOE) polymorphism in a family-based study. However, the association of A2M
      deletion polymorphism with AD has not been consistently replicated in successive
      case-controlled studies. In order to evaluate whether this A2M polymorphism is
      associated with AD in Koreans, we examined the frequencies of the A2M deletion
      (D) allele and D-bearing genotypes in a group of Koreans composed of 100 sporadic
      AD patients and 203 control subjects. The frequency of the deletion (D) allele
      (P=0.046) was significantly different between the total group of AD patients and
      the controls, although the frequency of the D-bearing genotypes did not attain
      significance (P=0.078). When the subjects were stratified according to age at
      onset, there was significant difference in the frequencies of the D allele
      (P=0.044) and D-bearing genotypes (P=0.041) between late-onset AD patients (> or
      =65 years) and the controls. However, no significant difference was observed
      between early-onset AD patients (<65 years) and the control group. Additionally,
      when we divided the late-onset AD and control subjects by APOE epsilon4 status,
      the difference of the A2M D allelic frequency was significant only in the APOE
      epsilon4 negative subjects (P=0.015). In conclusion, our data suggests that the
      A2M D allele is a modest risk factor for late-onset sporadic AD in Koreans, and
      the AD risk conferred by the A2M D allele increases in APOE epsilon4 negative
      subjects.

PMID- 11231029
TI  - Intravenous clomipramine decreases excitability of human motor cortex. A study
      with paired magnetic stimulation.
AB  - Several recent reports suggest the possibility of monitoring pharmacological
      effects on brain excitability through transcranial magnetic stimulation (TMS). In
      these studies, paired magnetic stimulation has been used in normal subjects and
      on patients who were taking different antiepileptic drugs. The aim of our study
      was to investigate motor area excitability on depressed patients after
      intravenous administration of a single dose of clomipramine, a tricyclic
      antidepressant. Motor cortex excitability was studied by single and paired
      transcranial magnetic stimulation (TMS) before and after 4, 8 and 24 h from
      intravenous administration of 25 mg of clomipramine. Cortical excitability was
      measured using different TMS parameters: motor threshold (MT), motor evoked
      potential (MEP) amplitude, duration of cortical silent period (CSP),
      intracortical inhibition (ICI) and intracortical facilitation (ICF). Spinal
      excitability and peripheral nerve conduction was measured by F response and M
      wave. A temporary but significant increase of motor threshold and intracortical
      inhibition and a decrease of intracortical facilitation were observed 4 h
      following drug administration. MEP amplitude, cortical silent period, F response
      and M wave were not significantly affected by drug injection. Our findings
      suggest that a single intravenous dose of clomipramine can exert a significant
      but transitory suppression of motor cortex excitability in depressed patients.
      TMS represents a useful research tool in assessing the effects of motor cortical
      excitability of neuropsychiatric drugs used in psychiatric disease.

PMID- 11231031
TI  - Demyelination and axonal damage in a non-human primate model of multiple
      sclerosis.
AB  - The demyelinating plaque is the paradigmatic lesion of multiple sclerosis (MS),
      but only recently attention has been given to axonal damage and to its role in
      the pathophysiology of disease. Albeit the possible relevance of axonal loss in
      MS and its experimental models, the amount and timing of axonal sufferance has
      been addressed only in experimental autoimmune encephalomyelitis (EAE) of
      rodents. In this report we observed that, in the marmoset model of EAE, axonal
      damage occurs early during the demyelinating process as assessed by
      immunoreactivity for amyloid precursor protein (APP) and non-phosphorylated
      neurofilaments (SMI-32 positive) detected mostly in early active lesions compared
      to late active and normal appearing white matter. The rare occurrence of
      morphological features of axonal transection, such as APP or SMI-32 positive
      spheroids and swellings, as well as an increase of neurofilament density in the
      demyelinated axons without accumulation of electron dense organelles or
      osmiophilic bodies, at electron microscopy, suggests that early axonal damage may
      be, at least in part, a reversible process. These findings are of relevance for
      the development of therapies, which can protect axons and enhance their function
      and survival.

PMID- 11231030
TI  - Prevalence and pattern of cognitive impairment in systemic lupus erythematosus
      patients with and without overt neuropsychiatric manifestations.
AB  - The prevalence and pattern of cognitive impairment in systemic lupus
      erythematosus (SLE) patients with (NPSLE) and without (nSLE) overt
      neuropsychiatric manifestations were investigated. Fifty-two nSLE patients, 23
      NPSLE patients and 27 healthy controls were evaluated with a battery of
      standardized neuropsychological and psychological tests. Disease duration,
      disease activity index, and current corticosteroid therapy were collected.
      Cognitive impairment was identified in 14 (26.9%) and in 12 (52.2%) of subjects
      with nSLE and NPSLE, respectively. Both SLE groups showed a significant
      impairment compared with controls on tasks assessing verbal and non-verbal long
      term memory, and visuoconstructional abilities. In addition, NPSLE patients
      reported worse performances than both nSLE patients and controls on task
      evaluating short-term visuospatial memory. NPSLE subjects were significantly more
      anxious and depressed compared to both nSLE subjects and controls. By
      multivariate analysis, only depression levels, among clinical variables,
      significantly predicted cognitive performance. This study shows that cognitive
      impairment occurs frequently in both nSLE and NPSLE subjects. The higher
      frequency in NPSLE may be related to coexisting depressive disturbances.

PMID- 11231032
TI  - Electrophysiologic endpoint measures in a multicenter ALS drug trial.
AB  - We report the analysis of a battery of secondary electrophysiologic measurements
      to assess the progression of amyotrophic lateral sclerosis (ALS) in a two center,
      six month, double-blind, three arm trial comparing branched chain amino acids to
      L-threonine with pyridoxal 5-phosphate to placebo. The endpoint measurements were
      chosen to separately assess the effects of lower motor neuron loss and collateral
      reinnervation. For tests of inter-center reliability, we found no differences
      that could not be readily explained by variations in electrophysiologic testing
      techniques. Since the drug study was negative for the primary endpoint measure
      (muscle strength), we combined data from both centers and the three treatment
      arms. For measures of progression, all measures changed in the expected direction
      during the 6 months of the trial. We conclude that a battery of
      electrophysiologic measures can be used in a multicenter ALS drug trial to
      provide information on changes in lower motor neuron numbers and the effects of
      collateral reinnervation.

PMID- 11231033
TI  - Age of onset influences clinical features of chronic inflammatory demyelinating
      polyneuropathy.
AB  - Chronic inflammatory demyelinating polyneuropathy (CIDP), which can occur through
      life from childhood to old age, presents a wide variety of clinical phenotypes.
      We investigated the relationship between age of onset and phenotype in 124 CIDP
      patients. Clinical symptoms, pathologic findings and electrophysiologic features
      were assessed according to age at onset: juvenile, younger than 20-years-old;
      adult, 20 to 64; and elderly, older than 64 (total n=124). Half of the juvenile
      group showed subacute progression initially, while most patients in the elderly
      group showed chronic insidious progression (chi(2)=23.2, P<0.0001). Motor
      dominant neuropathy was prominent in juveniles, while sensorimotor neuropathy was
      frequent in the elderly group (chi(2)=27.0, P<0.0001). A relapsing and remitting
      course predominated in the juvenile group (chi(2)=8.50, P=0.0143). Demyelinating
      and axonal degenerating features in sural nerve biopsy and in nerve conduction
      studies were common to three age groups. The subperineurial edema was more
      prominent in the juvenile and adult groups (P=0.006). Functional recovery was
      common in all three age groups, but was least apparent in the elderly group
      (P=0.00062). Demyelinating features in studies of nerve conduction and biopsy
      specimens was common to all three age groups, and was a useful diagnostic
      feature. Clinical features of CIDP differ by age of onset, which is a factor to
      consider in diagnosis, therapy, and prognosis.

PMID- 11231034
TI  - Clinical features, EEG findings and diagnostic pitfalls in juvenile myoclonic
      epilepsy: a series of 63 patients.
AB  - Juvenile myoclonic epilepsy (JME) is a common idiopathic generalized epileptic
      syndrome distinctively characterized by myoclonic jerks often associated to
      generalized tonic-clonic seizures (GTCS) and typical absence seizures. In spite
      of typical clinical and EEG profiles, JME is widely underdiagnosed. In the
      present study we retrospectively revised clinical and EEG data of JME patients
      referring to our Epilepsy Service. A diagnosis of JME could be made in 63
      patients, that is 5.7% of all the epileptic patients referring to our Service and
      25.9% of those suffering from an idiopathic generalized epilepsy. General
      features as well as modality of onset and course of the syndrome of our JME
      subjects were in accordance with literature. Regarding EEG findings, asymmetries
      were detected in 38.1% of cases. At referral to our Service only 31.7% of JME
      patients were correctly diagnosed. Main factors responsible for misdiagnosis were
      failure in eliciting a history of myoclonic jerks and misinterpretation of
      myoclonic jerks as simple partial seizures. EEG asymmetries were misleading in 13
      patients. In conclusion, a correct JME diagnosis is strictly dependent on the
      knowledge of the syndrome leading the interviewer to look for and correctly
      interpret myoclonic jerks whereas EEG is just an ancillary diagnostic tool.

PMID- 11231035
TI  - Glial involvement in the degeneration process of Lewy body-bearing neurons and
      the degradation process of Lewy bodies in brains of dementia with Lewy bodies.
AB  - Glial involvement in the degeneration process of Lewy body (LB)-bearing neurons
      and the degradation process of LBs in the cerebral cortex and amygdala in brains
      of dementia with Lewy bodies was investigated immunohistochemically. HLA-DR
      positive microglia frequently extended their processes to degenerated neurons
      with alpha-synuclein-positive LBs, while some GFAP-positive astroglial processes
      attached to weakly alpha-synuclein-positive extracellular LBs. Some intracellular
      LBs were immunoreactive to anti-C4d antibody, and these LB-bearing neurons were
      involved by activated microglia. About half of the intracellular LBs were
      immunoreactive to anti-chromogranin-A (CGA) antibody, and most of CGA-positive LB
      bearing neurons were surrounded by microglia. Although we could find no evident
      participation of TNF-alpha, a candidate cytokine that is up-regulated by
      microglia following CGA stimulation, in the degeneration process of LB-bearing
      neurons, some intracellular LBs were immunoreactive to the antibody to NF-kappaB,
      a transcriptional factor activated by cytokines. These findings suggest that
      microglia participate in the degeneration process of LB-bearing neurons via
      varying immunogenic elements including complement proteins, CGA and probably some
      cytokines, and that astroglia participate in the degradation process of LBs.

PMID- 11231036
TI  - Effects of slow repetitive transcranial magnetic stimulation on heart rate
      variability according to power spectrum analysis.
AB  - We examined whether repetitive transcranial magnetic stimulation (rTMS) at a low
      rate could influence autonomic function, specially heart rate variability (HRV)
      by power spectrum analysis. We studied 16 healthy male volunteers as a
      stimulation group and 16 others as a sham group. The stimulation group received
      magnetic stimulations from a circular coil over Cz at a frequency of 0.2 Hz and
      an intensity presenting 90% of the motor threshold. Experiments in both groups
      included four daily sessions; at each, a train of 70 stimuli was delivered over
      350 s. HRV of low-frequency power (LF) in a standing position and high-frequency
      power (HF) in a supine position were measured before and after each session.
      After stimulation, HF and LF powers were significantly increased. After sham
      stimulation, the power of HF but not that of LF significantly increased. Neither
      actual nor sham stimulation produced a long-term effect detectable on day 5. The
      finding of transiently increased LF power following actual but not sham
      stimulation suggests that rTMS may activate the sympathetic nervous system.

PMID- 11231037
TI  - Hyperthyroid dementia: clinicoradiological findings and response to treatment.
AB  - Dementia associated with hyperthyroidism is less well documented than is
      hypothyroid dementia. Therapeutic response of hyperthyroid dementia and
      associated cerebral circulatory and/or metabolic abnormalities has not been
      elucidated. We described a patient with hyperthyroid dementia and
      clinicoradiological response to treatment. Single photon emission computed
      tomographic (SPECT) study was repeated and analyzed semiquantitatively. A 67-year
      old man experienced progressive impairments of attention, memory, constructive
      skills and behavior as well as hand tremor and weight loss of two-year duration.
      Laboratory findings were compatible with Graves' disease. The initial SPECT
      showed diffuse tracer uptake defect with an accentuation in the bilateral
      temporoparietal regions. Clinical and SPECT findings both suggested concurrent
      "possible" Alzheimer's disease. However, initial treatment with a beta-blocker
      improved behavior and attention-related cognitive functions as well as tracer
      uptake in the frontal lobes. Subsequent treatment with additional methimazole
      then improved memory and constructive abilities when a euthyroid state was
      established. Uptake defect in the temporoparietal regions also responded
      gradually to the medication. We suggest that the present patient represent
      hyperthyroid dementia, which responds favorably to treatment with regard to
      clinical symptoms and SPECT findings. We also suggest that thyroid function be
      measured in patients with "possible" Alzheimer's disease because treatable
      hyperthyroid dementia may not be identified.

PMID- 11231038
TI  - A regulatory role for neurokinin B in placental physiology and pre-eclampsia.
AB  - Tachykinin dogma has assumed, so far, that neurokinin B (NKB) is a neuropeptide
      that is not produced in any peripheral tissue even though its endogenous
      receptor, NK3, has been found in a number of locations throughout the human body.
      We have found an abundant source of peripheral NKB in the human and rat placenta.
      In this review we describe the discovery of NKB in the placenta and examine its
      possible role in placental physiology and pre-eclampsia (PE). Excessive secretion
      of placental NKB into the maternal circulation during the third trimester of
      pregnancy has been found in women suffering from PE. This may provide the key to
      the cause of the multiple and complex symptoms associated with this potentially
      life-threatening illness. We also reveal the structural organisation of the human
      NKB gene for the first time as well as discussing putative mechanisms for its
      control.

PMID- 11231040
TI  - Effect of nitric oxide on basal and stretch-induced release of atrial natriuretic
      factor (ANF) from isolated perfused rat atria.
AB  - We investigated the effect of the NO donor SNAP (6.7 nM) on basal and stretch
      induced ANF release from isolated perfused rat atria. There was no significant
      difference in basal ANF secretion between the vehicle- and SNAP-infused atria
      (SNAP: 388+/-63 pg. 100 microl(-1), n = 13 vs. vehicle: 349+/-26 pg. 100 microl(
      1), n = 5). Atrial distention caused an increase in ANF secretion in both the
      buffer- and SNAP-treated groups. SNAP greatly attenuated the stretch-induced
      increase in ANF (SNAP: 225+/-7 pg. 100 microl(-1), n = 5 vs. vehicle: 448+/-72
      pg. 100 microl(-1), n = 13, P < 0.05). The compliance of atria treated with SNAP
      was lower than that of the vehicle-perfused atria (P < 0.05). Thus, although SNAP
      appeared to attenuate stretch-induced ANF secretion, there was in fact no
      significant difference in the ratio of Delta[ANF] to Deltaintraluminal volume
      (SNAP: 5.8+/-1.3 pg. 100 microl(-1). microl(-1) vs. vehicle: 8.2+/-1.4 pg. 100
      microl(-1). microl(-1).). In conclusion, we found no evidence that NO alters the
      control of basal or stretch-induced ANF secretion. NO can however reduce ANF
      release by shifting the pressure-volume curve, so that a given increase in atrial
      pressure is associated with a smaller increase in intraluminal volume and reduced
      atrial distention.

PMID- 11231039
TI  - Role of nitric oxide on atrial natriuretic peptide release induced by angiotensin
      II in superfused rat atrial tissue.
AB  - The present study investigated the role of nitric oxide (NO) on atrial
      natriuretic peptide (ANP) release stimulated by angiotensin II (Ang II) (10(-7)
      M) in superfused sliced rat atrial tissue. The use of N(G)-nitro-L-arginine
      methyl ester (L-NAME) at 10(-4) M, an inhibitor of nitric oxide synthase did not
      modify basal ANP release. In presence of Ang II (10(-7) M), we observed that L
      NAME enhanced ANP secretion induced by Ang II. Furthermore, cGMP levels increased
      significantly in the presence of Ang II and was attenuated by L-NAME. On the
      other hand, the perfusion of 8 bromo-cGMP (10(-5) M) with Ang II reduced the
      effect of this octapeptide on ANP secretion. Secondly, we evaluated the effect of
      authentic NO on ANP release and observed that perfusion of NO reduced
      significantly the effect of Ang II on ANP release. We propose that the effect of
      Ang II on ANP secretion was modulated by NO likely via cGMP pathway.

PMID- 11231041
TI  - Substance P (NK1) receptor in relation to substance P innervation in rat duodenum
      after irradiation.
AB  - It has previously been shown that high dose of irradiation to the rat abdomen
      leads to an increased level of substance P (SP) in the duodenum. In the present
      study the pattern of distribution of NK1 receptors (NK1-R) in rat duodenum after
      irradiation (5-30 Gy), was examined at the same time-point (7 days) after
      irradiation, comparisons being made with the distribution of SP-innervation.
      Immunohistochemical methods were used. In controls, NK1-R-like immunoreactivity (
      LI) was detected in epithelial cells, in cells in the region of the intestinal
      cells of Cajal within the deep muscular plexus (ICC-DMP), in neuronal cells in
      the myenteric plexus, and variably in granulocytes in the mucosa. Irradiation
      with 5-10 Gy did not lead to obvious changes in the pattern of NK1-R-LI. After
      irradiation with the highest doses (25-30 Gy), the mucosa was often gravely
      damaged, displaying granulation tissue. No epithelial NK1-R-LI was detected in
      this tissue, but was present in less affected mucosa after these doses. In the
      region of the ICC-DMP, in the myenteric plexus, and in granulocytes, NK1-R-LI was
      detected also after high dose irradiation. However, the degree of NK1-R-LI in the
      region of the ICC-DMP was somewhat lower than seen in controls and after low
      doses. SP-immunoreactive nerve fibers were present in the regions where NK1-R-LI
      was detected. These findings support a suggestion that an increased level of SP
      after irradiation may contribute to the dose-dependent gastrointestinal adverse
      effects that occur after radiotherapy.

PMID- 11231042
TI  - Atypical angiotensin receptors may mediate water intake induced by central
      injections of angiotensin II and of serotonin in pigeons.
AB  - Intracerebroventricular (i.c.v.) injection of serotonin (5-HT) in pigeons dose
      dependently evokes a prompt and intense drinking behavior, which resembles that
      evoked by i.c.v. injections of angiotensin II (ANGII) in the same species. In the
      present study, we have examined the possible participation of central ANGII
      receptors in both ANGII- and 5-HT-evoked drinking behavior. The effects of i.c.v.
      injections of 5-HT (155 nmol), avian ANGII ([Asp(1),Val(5)]-ANGII, 0.1 nmol) or
      vehicle were studied in pigeons pretreated 20 min before with i.c.v. injections
      of the nonspecific ANGII receptor antagonist [Sar(1),Ile(8)]-ANGII (SAR; 1, 0.1
      or 0.01 nmol), the AT(1) receptor antagonist losartan (2 or 4 nmol), the AT(2)
      receptor antagonist PD 123,319 (2 or 4 nmol) or vehicle (NaCl 0.15 M, 1 microl, n
      = 8/group). Immediately after treatment, they were given free access to water and
      drinking behavior was recorded during the next 60 min. At the doses presently
      used both 5-HT and ANGII treatments evoked comparable water intake amounts with
      similar behavioral profiles. While pretreatment with SAR dose-dependently reduced
      the water intake evoked by both 5-HT and ANGII, neither losartan nor PD 123,319
      pretreatment affected the drinking induced by these treatments. The present
      results indicate that ANGII- and 5-HT-induced drinking in pigeons may be mediated
      by AT receptors possibly different from mammalian AT(1) and AT(2) receptors and
      suggest that activation of ANGII central circuits is a necessary step for the
      intense drinking induced by i.c.v. injections of 5-HT in this species.

PMID- 11231043
TI  - Localisation and neural control of the release of calcitonin gene-related peptide
      (CGRP) from the isolated perfused porcine ileum.
AB  - By immunohistochemistry, CGRP-like immunoreactive (CGRP-LI) nerve fibres were
      found in the lamina propria along small vessels and in the lamina muscularis
      mucosae in the porcine ileum. Immunoreactive nerve cell bodies were found in the
      submucous and myenteric plexus. Upon HPLC-analysis of ileal extracts, CGRP-LI
      corresponded entirely to porcine CGRP plus smaller amounts of oxidised CGRP.
      Using isolated vascularly perfused segments of the ileum, we studied the release
      of CGRP-LI in response to electrical stimulation of the mixed extrinsic
      periarterial nerves and to infusion of different neuroblockers. In addition, the
      effect of infusion of capsaicin was studied. The basal output of CGRP-LI was
      2.9+/-0.7 pmol/5 min (mean+/-S.D.). Electrical nerve stimulation (8 Hz)
      significantly increased the release of CGRP-LI to 167+/-16% (mean+/-S.E.M.) of
      the basal output (n=13). This response was unaffected by the addition of atropine
      (10(-6) M). Nerve stimulation during infusion of phentolamine (10(-5) M) with and
      without additional infusion of atropine resulted in a significant further
      increase in the release of CGRP-LI to 261+/-134% (n=5) and 240+/-80% (n=9),
      respectively. This response was abolished by infusion of hexamethonium (3x10(-5)
      M). Infusion of capsaicin (10(-5) M) caused a significant increase in the release
      of CGRP-LI to 485+/-82% of basal output (n=5). Our results suggest a dual origin
      of CGRP innervation of the porcine ileum (intrinsic and extrinsic). The intrinsic
      CGRP neurons receive excitatory input by parasympathetic, possibly vagal,
      preganglionic fibres, via release of acetylcholine acting on nicotinic receptors.
      The stimulatory effect of capsaicin suggests that CGRP is also released from
      extrinsic sensory neurons.

PMID- 11231044
TI  - Endothelin receptors in human and guinea-pig gallbladder muscle.
AB  - We measured contraction of muscle strips caused by endothelin (ET) isopeptides
      and binding of (125)I-ET-1 to muscle cell membranes prepared from human and
      guinea-pig gallbladders. Visualization of (125)I-ET-1 binding sites in tissue was
      performed by autoradiography. Results in human were similar to those in guinea
      pig. ET-1 caused tetrodotoxin and atropine-insensitive contraction. The relative
      potencies for ET isopeptides to cause contraction were ET-1=ET-2>ET-3. ET-1
      caused contraction was only slightly inhibited by BQ-123 (potent ET(A) receptor
      antagonist) and not by BQ-788 (potent ET(B) receptor antagonist). It was
      inhibited by the combination of both. Autoradiography localized (125)I-ET-1
      binding to the smooth muscle layer. Binding of (125)I-ET-1 to muscle cell
      membranes was saturable and specific. Analysis of dose-inhibition curves
      demonstrated the presence of two classes of receptors. One class (ET(A) receptor)
      had a high affinity for ET-1 and ET-2 but a low affinity for ET-3, and the other
      (ET(B) receptor) a high affinity for ET-1, ET-2 and ET-3. These results
      demonstrate that similar to guinea-pig, human gallbladder possesses both ET(A)
      and ET(B) receptors cooperating to mediate muscle contraction.

PMID- 11231045
TI  - A molecular modeling and 3D QSAR study of a large series of indole inhibitors of
      human non-pancreatic secretory phospholipase A2.
AB  - Automated docking allowing protein-based alignment was performed for a series of
      188 indole inhibitors of the human non-pancreatic secretory phospholipase A2
      (hnps-PLA2). All the substituted indoles were docked to the crystal structure of
      hnps-PLA2 and a three-dimensional QSAR model was then established using the CoMFA
      method. The set of 188 compounds was divided into two subsets, the first one
      constituting the training set (126 compounds), while the second constituted the
      test set (62 compounds). The established CoMFA model derived from the training
      set was then applied to the test set. A good correlation between predicted and
      experimental activity data allows to validate the 3D QSAR model. A second and
      global 3D QSAR including all the compounds was established, allowing the creation
      of the hnps-PLA2 pharmacophore.

PMID- 11231047
TI  - Antihyperglycemic activity of new 1,2,4-oxadiazolidine-3,5-diones.
AB  - A series of 1,2,4-oxadiazolidine-3,5-diones was synthesized and evaluated as oral
      antihyperglycemic agents in the obese insulin resistant db/db and ob/ob mouse -
      the two models for Type 2 diabetes mellitus. The majority of the prepared methoxy
      and ethoxy-linked oxazole 1,2,4-oxadiazolidine-3,5-diones normalized plasma
      glucose levels at the 100 mg kg(-1) oral dose in the db/db diabetic mouse model,
      and several amongst them reduced the glucose levels at the 20 mg kg(-1) oral
      dose. The most potent compounds in the db/db mouse model were also active in the
      ob/ob mouse model normalizing the plasma glucose levels at the 20 mg kg(-1) oral
      dose. The trifluoromethoxy analog 32 was the most active compound of the series,
      reducing significantly the plasma glucose levels at the 5 mg kg(-1) oral dose.
      Oxadiazole-tailed 1,2,4-oxadiazolidine-3,5-diones were also active in both the
      db/db and ob/ob diabetic mouse models normalizing plasma glucose levels at the
      100 mg kg(-1) oral dose.

PMID- 11231046
TI  - Protein-based alignment in 3D QSAR of 26 indole inhibitors of human pancreatic
      phospholipase A2.
AB  - An automated docking procedure was applied on a series of 26 reversible and
      competitive indole inhibitors of human pancreatic phospholipase A2 (hp-PLA2). X
      ray data of this enzyme are not available and the structure was then
      reconstructed exploiting its protein sequence and the crystallographic data of a
      bovine pancreatic source. The docking data were used to build a three-dimensional
      quantitative structure-activity relationship (3D QSAR) model, established using
      the comparative molecular field analysis (CoMFA) method. This model, joined to
      the previous one developed for the indole inhibitors of human non-pancreatic
      secretory phospholipase A2 (hnps-PLA2), an enzyme involved in inflammation
      processes, will allow for the selection of new strong anti-inflammatory drugs
      with negligible side effects, at least at the level of hp-PLA2.

PMID- 11231048
TI  - Conformationally constrained analogues of endogenous tripeptide inhibitors of
      zinc metalloproteinases.
AB  - Two diastereomeric furan-2-carbonylamino-3-oxohexahydroindolizino[8,7-b]indole
      carboxylates, highly constrained analogues of endogenous pyroglutamyl tripeptide
      inhibitors of snake venom endopeptidases, have been prepared as potential
      inhibitors of adamalysin II and matrix metalloproteinases. They proved to be
      inactive against adamalysin II and weak inhibitors of gelatinase A, gelatinase B,
      stromelysin 1 and human neutrophil collagenase. Evaluation of the mode of binding
      of the (2R,5S,11bR) isomer in the active site of adamalysin II suggests that the
      decrease of potency may be due to the reorientation of the acylamino chain in
      three of the heterocyclic nucleus, to a short contact at the entrance of the
      S'(1) hydrophobic cleft and to the loss of flexibility of the tetracyclic nucleus
      in the P'(1), P'(2) region of the inhibitor, which prevents optimal arrangement
      in the S'(1) specificity subsite.

PMID- 11231049
TI  - New 3-[4-(aryl)piperazin-1-yl]-1-(benzo[b]thiophen-3-yl)propane derivatives with
      dual action at 5-HT1A serotonin receptors and serotonin transporter as a new
      class of antidepressants.
AB  - A series of new 3-[4-(aryl)piperazin-1-yl]-1-(benzo[b]thiophen-3-yl)propane
      derivatives were synthesized in an attempt to find a new class of antidepressant
      drugs with dual activity at 5-HT1A serotonin receptors and serotonin transporter.
      Title compounds were evaluated for in vitro activity on 5-HT1A receptor and 5-HT
      transporter. They show high nanomolar affinity for both activities, and in
      particular, compounds 1-(5-chlorobenzo[b]thiophen-3-yl)-3-[4-(2
      methoxyphenyl)piperazin-1-yl]propan-1-ol (7) and 1-(5-fluorobenzo[b]thiophen-3
      yl)-3-[4-(2-methoxyphenyl)piperazin-1-yl]propan-1-ol (8) show values (nM) of
      K(i)=30 and 2.3 for 5-HT1A receptors and K(i)=30 and 12 for serotonin
      transporters, respectively. In GTPgammaS binding assays, compound 8 revealed
      antagonist properties to 5-HT1A receptors. Such a pharmacological profile could
      lead to potent antidepressant agents with new dual mechanism of action.

PMID- 11231050
TI  - Prodrugs of butyric acid. Novel derivatives possessing increased aqueous
      solubility and potential for treating cancer and blood diseases.
AB  - The synthesis and biological activities of acidic, basic and neutral types of
      butyric acid (BA) prodrugs possessing increased aqueous solubility are described.
      The compounds are butyroyloxyalkyl derivatives of carboxylic acids, which possess
      functionalities suitable for aqueous solubilization. The anticancer activity of
      the prodrugs in vitro was evaluated by examining their effect on the growth of
      human colon, breast and pancreatic carcinoma cell lines, and their solubility in
      aqueous media was determined. The most promising compounds, with respect to
      activity and solubility, were found to be the butyroyloxymethyl esters of
      glutaric 2a and nicotinic acids 4a and phosphoric acid as its diethyl ester 10a,
      which displayed IC(50) values of 100 microM or lower. These prodrugs are expected
      to release formaldehyde upon metabolic hydrolysis. The corresponding
      butyroyloxyethyl esters (2b, 4b and 10b) that release acetaldehyde upon
      metabolism were significantly less potent. A similar correlation was observed for
      growth inhibition of the human prostate carcinoma cell lines PC-3 and LnCap and
      for induction of differentiation and apoptosis in the human myeloid leukemia cell
      line HL-60. The higher biological activity of the formaldehyde-releasing prodrugs
      2a and 10a was further confirmed when induction of hemoglobin (Hb) synthesis in
      the human erythroleukemic cell line K562 was measured. Moreover, a therapeutic
      index (IC(50)/ED(50)) of ca. 5 was observed. The acute i.p. toxicity LD(50) in
      mice for 2a, 2b, 10a and 10b was similar and in the range of 400-600 mg kg(-1).
      The results obtained support the potential use of the butyric acid prodrugs for
      the treatment of neoplastic diseases and beta-globin disorders.

PMID- 11231051
TI  - Synthesis and mycological activity of the compounds obtained in the reaction of
      N(3)-substituted amidrazones with sulphinyl-bis-2,4-dihydroxybenzenethioyl.
AB  - 2-Phenyl-5-(2,4-dihydroxybenzene)-1,3,4-thiadiazole (4), 2-(2-pyridyl)-2,4
      dihydroxybenzene-1,3,4-thiadiazole (5), N(1)-2,4-dihydroxybenzenecarbothio-N(3)
      phenyl-benzamidrazone (6) and N(1)-2,4-dihydroxybenzenecarbothio-N(3)-phenyl-2
      picoline-amidrazone (7) were prepared and tested for their antimycotic activity.
      The chemical structures were confirmed by IR, 1H-NMR, EI-MS and elemental
      analysis. The minimal inhibitory concentration (MIC) values against
      dermatophytes, yeasts and moulds were determined for the estimation of potential
      activity in vitro. The strongest fungistatic activity for compound 5 in relation
      to dermatophytes was found with MIC 0.48-0.99 microg mL(-1).

PMID- 11231052
TI  - Synthesis and anti-inflammatory activity of 1-acetyl-5-substituted aryl-3-(beta
      aminonaphthyl)-2-pyrazolines and beta-(substituted aminoethyl) amidonaphthalenes.
AB  - The title compounds were prepared by reaction of beta-acetylamino-naphthalene
      with different aromatic aldehydes followed by cyclisation with hydrazine hydrate
      and with different primary or secondary amines (Mannich's reaction),
      respectively. The structures of new compounds were confirmed by 1H-NMR and IR
      spectral data. Anti-inflammatory and ulcerogenic activities in vivo were
      evaluated and compared with the standard drugs, phenylbutazone and indomethacin.
      Some compounds of the series exhibited promising anti-inflammatory activity with
      a lower ulcerogenic liability than the standard drugs.

PMID- 11231053
TI  - Antiviral activity of the products of cyclization of dimethyl 2-[(1-arylamino-1
      arylmethylidene)hydrazono]succinate.
AB  - In this research, conditions of cyclization of dimethyl 2-[(1-arylamino-1
      arylmethylidene)hydrazono]succinate 1-5 leading to the formation of 3,4-diaryl-5
      carboxymethyl-1,2,4-triazole 6-10 and methyl 2-(5-oxo-3,4-diaryl-1,4,5,6
      tetrahydro-1,2,4-triazine-6-ylidene)acetates 11-15 and the biological activity of
      some of them have been examined. Their chemical structures were confirmed by IR,
      1H-NMR, EI-MS and elemental analysis. Substances 8 and 13 exhibited moderate
      virucidal activity and partially inhibited absorption of the viruses to the
      susceptible cells. The acute toxicity of compounds 6-10 was established. For
      compounds 8 and 13, the influence on the central nervous system of mice and rats
      in behavioral tests was examined.

PMID- 11231054
TI  - Stem cells and the regulation of proliferation, differentiation and patterning in
      the intestinal epithelium: emerging insights from gene expression patterns,
      transgenic and gene ablation studies.
AB  - Tissues that undergo self-renewal such as the skin, the haematopoeitic system and
      the intestine are all maintained and renewed by a small group of multipotent stem
      cells. The stem cells of the intestinal epithelium are located in the crypts and
      give rise to its four main lineages located mainly in the finger like projections
      the villi. An increasing number of genes are now being identified as either
      being necessary for or involved in the maintenance of intestinal stem cells and
      regulating differentiation along the crypt-villus axis. These developmental
      regulatory genes include among others, Tcf-4, Cdx-1 Fkh6, HFH11 and Nkx2-3. Other
      genes such as the integrins, and Indian hedgehog (Ihh) also affect function of
      the progenitor cells of the intestinal epithelium. This mini-review will focus on
      the more recent data on expression patterns of genes in the intestinal epithelium
      and the direct or indirect effects of their ablation on proliferation and
      differentiation.

PMID- 11231055
TI  - DNA array analysis of the developing rat cerebellum: transforming growth factor
      beta2 inhibits constitutively activated NF-kappaB in granule neurons.
AB  - The nuclear factor-kappaB (NF-kappaB) pathway is important in neuronal survival
      and in integration of external signals e.g. cytokines, glutamate, Abeta and nerve
      growth factor (NGF). During rat cerebellar development NF-kappaB activity is high
      in granule cells before postnatal day 7 (P7) and declines after P7. Using gene
      expression profiles, measured by cDNA arrays, up-regulation of transforming
      growth factor-beta2 (TGF-beta2) was correlated with the developmental down
      regulation of NF-kappaB. TGF-beta2 depicted strongest, more than 4-fold, up
      regulation in P12 versus P4 cerebella. In situ hybridization and
      immunohistochemistry confined upregulated TGF-beta2 to granule cells and
      correlated mRNA and TGF-beta2-protein increase. Finally TGF-beta2 repressed NF
      kappaB activity, in an in vitro system resembling migrating cerebellar granule
      cells. Thus, TGF-beta might fulfill an important role in repressing
      developmentally activated NF-kappaB in granule neurons.

PMID- 11231056
TI  - NudE-L, a novel Lis1-interacting protein, belongs to a family of vertebrate
      coiled-coil proteins.
AB  - The LIS1-encoded protein (Lis1) plays a role in brain development because a
      hemizygous deletion or mutation of the human gene causes neuronal migration
      disorders, such as Miller-Dieker syndrome (MDS) or isolated lissencephaly
      sequence (ILS). Using a yeast two-hybrid screen, we have isolated a novel protein
      that interacts with mouse Lis1 (mLis1) which is termed mouse NudE-like protein
      (mNudE-L) because of its 49% amino acid conservation with NudE, a protein
      involved in nuclear migration in Aspergillus nidulans. GST pull-down assays and
      co-immunoprecipitation of fusion proteins expressed in mammalian cells confirmed
      the interaction of mLis1 and mNudE-L. mNudE-L gives rise to a approximately 2.3
      kb mRNA and encodes an ORF corresponding to approximately 38 kDa protein. The
      overall amino acid sequence of mNudE-L is 49-95% identical to proteins found in a
      variety of organisms, thus establishing mNudE-L as a new member of a protein
      family. The hallmark of this family is an N-terminal region predicted to form a
      coiled-coil domain. We show that mNudE-L and mLis1 are coexpressed in the
      postnatal and adult cerebral cortices and in the Purkinje neurons of the
      cerebellum. In contrast to mLis1, mNudE-L transcripts are absent in the mitral
      cell layer of the olfactory bulb and in the inward migrating granular neurons of
      the developing cerebellum. Mutant mLis1 proteins modelling mutations found in
      human lissencephaly patients fail to interact with mNudE-L, raising the
      possibility that phenotypic changes result, in part, from the inability of mutant
      Lis1 proteins to interact with the human NudE-L polypeptide.

PMID- 11231057
TI  - Spatially and temporally regulated expression of myosin heavy chain alternative
      exons during Drosophila embryogenesis.
AB  - We used alternative exon-specific probes to determine the accumulation of
      transcripts encoding myosin heavy chain (MHC) isoforms in Drosophila melanogaster
      embryos. Six isoforms accumulate in body wall muscles. Transverse (external)
      muscles express a different major form than intermediate and internal muscles,
      suggesting different physiological properties. Cardioblasts express one of the
      somatic muscle transcripts; visceral muscles express at least two transcript
      types. The pharyngeal muscle accumulates a unique Mhc transcript, suggesting
      unique contractile abilities. Mhc transcription begins in stage 12 in visceral
      and somatic muscles, but as late as stage 15 in cardioblasts. This is the first
      study of myosin isoform localization during insect embryogenesis, and forms the
      basis for transgenic and biochemical experiments designed to determine how MHC
      domains regulate muscle physiology.

PMID- 11231058
TI  - Transcription factors in melanocyte development: distinct roles for Pax-3 and
      Mitf.
AB  - A transgenic mouse model was used to examine the roles of the murine
      transcription factors Pax-3 and Mitf in melanocyte development. Transgenic mice
      expressing beta-galactosidase from the dopachrome tautomerase (Dct) promoter were
      generated and found to express the transgene in developing melanoblasts as early
      as embryonic day (E) 9.5. These mice express the transgene in a pattern
      characteristic of endogenous Dct expression. Transgenic mice were intercrossed
      with two murine coat color mutants, Splotch (Sp), containing a mutation in the
      murine Pax3 gene, and Mitf(mi), with a mutation in the basic-helix-loop-helix
      leucine zipper gene Mitf. Transgenic heterozygous mutant animals were crossed to
      generate transgenic embryos for analysis. Examination of beta-galactosidase
      expressing melanoblasts in mutant embryos reveals that Mitf is required in vivo
      for survival of melanoblasts up to the migration staging area in neural crest
      development. Examination of Mitf(mi)/+ embryos shows that there are diminished
      numbers of melanoblasts in the heterozygous state early in melanocyte
      development, consistent with a gene dosage-dependent effect upon cell survival.
      However, quantification and analysis of melanoblast growth during the migratory
      phase suggests that melanoblasts then increase in number more rapidly in the
      heterozygous embryo. In contrast to Mitf(mi)/Mitf(mi) embryos, Sp/Sp embryos
      exhibit melanoblasts that have migrated to characteristic locations along the
      melanoblast migratory pathway, but are greatly reduced in number compared to
      control littermates. Together, these results support a model for melanocyte
      development whereby Pax3 is required to expand a pool of committed melanoblasts
      or restricted progenitor cells early in development, whereas Mitf facilitates
      survival of the melanoblast in a gene dosage-dependent manner within and
      immediately after emigration from the dorsal neural tube, and may also directly
      or indirectly affect the rate at which melanoblast number increases during
      dorsolateral pathway migration.

PMID- 11231059
TI  - Generation of a prostate epithelial cell-specific Cre transgenic mouse model for
      tissue-specific gene ablation.
AB  - To facilitate the elucidation of the genetic events that may play an important
      role in the development or tumorigenesis of the prostate gland, we have generated
      a transgenic mouse line with prostate-specific expression of Cre recombinase.
      This line, named PB-Cre4, carries the Cre gene under the control of a composite
      promoter, ARR2PB which is a derivative of the rat prostate-specific probasin (PB)
      promoter. Based on RT-PCR detection of Cre mRNA in PB-Cre4 mice or Cre-mediated
      activation of LacZ activity in PB-Cre4/R26R double transgenic mice, it is
      conclusively demonstrated that Cre expression is post-natal and prostatic
      epithelium-specific. Although the Cre recombination is detected in all lobes of
      the mouse prostate, there is a significant difference in expression levels
      between the lobes, being highest in the lateral lobe, followed by the ventral,
      and then the dorsal and anterior lobes. Besides the prostate gland, no other
      tissues of the adult PB-Cre4 mice demonstrate significant Cre expression, except
      for a few scattered areas in the gonads and the stroma of the seminal vesicle. By
      crossing the PB-Cre4 animals with floxed RXRalpha allelic mice, we demonstrate
      that mice, whose conventional knockout of this gene is lethal in embryogenesis,
      could be propagated with selective inactivation of RXRalpha in the prostate.
      Taken together, the results show that the PB-Cre4 mice have high levels of Cre
      expression and a high penetrance in the prostatic epithelium. The PB-Cre4 mice
      will be a useful resource for genetic-based studies on prostate development and
      prostatic disease.

PMID- 11231060
TI  - Mitochondrial small ribosomal RNA is a component of germinal granules in Xenopus
      embryos.
AB  - Mitochondrial large rRNA (mtlrRNA) and small rRNA (mtsrRNA) have been identified
      as components of germinal granules in Drosophila. We have previously reported
      that mtlrRNA is present on the germinal granules in Xenopus embryos. Here we
      report that mtsrRNA is also a common component of the germinal granules. Extra
      mitochondrial mtsrRNA is localized on the surface of germinal granules in germ
      plasm from four-cell to blastula stage, then disappears until the completion of
      gastrulation. This temporal and spatial distribution pattern is identical to that
      of mtlrRNA. During the stages when both mitochondrial rRNAs are present around
      the germinal granules, mitochondrial-type ribosomes, typified by their smaller
      size, were also present on the surface of the germinal granules.

PMID- 11231061
TI  - Regulation of pattern formation in the Drosophila hindgut by wg, hh, dpp, and en.
AB  - The hindgut of the Drosophila embryo is subdivided into three major domains, the
      small intestine, large intestine, and rectum, each of which is characterized by
      specific gene expression. Here we show that the expression of wingless (wg),
      hedgehog (hh), decapentaplegic (dpp), and engrailed (en) corresponds to the
      generation or growth of particular domains of the hindgut. wg, expressed in the
      prospective anal pads, is necessary for activation of hh in the adjacent
      prospective rectum. hh is expressed in the prospective rectum, which forms
      anteriorly to the anal pads, and necessary for the expression of dpp at the
      posterior end of the adjacent large intestine. wg and hh are also necessary for
      the development of their own expression domains, anal pads, and rectum,
      respectively. dpp, in turn, causes the growth of the large intestine, promoting
      DNA replication. en defines the dorsal domain of the large intestine, repressing
      dpp in this domain. A one-cell-wide domain, which delineates the anterior and
      posterior borders of the large intestine and its internal border between the
      dorsal and ventral domains, is induced by the activity of en. We propose a model
      for the gene regulatory pathways leading to the subdivision of the hindgut into
      domains.

PMID- 11231062
TI  - Increased XRALDH2 activity has a posteriorizing effect on the central nervous
      system of Xenopus embryos.
AB  - Retinoic acid (RA) metabolizing enzymes play important roles in RA signaling
      during vertebrate embryogenesis. We have previously reported on a RA degrading
      enzyme, XCYP26, which appears to be critical for the anteroposterior patterning
      of the central nervous system (EMBO J. 17 (1998) 7361). Here, we report on the
      sequence, expression and function of its counterpart, XRALDH2, a RA generating
      enzyme in Xenopus. During gastrulation and neurulation, XRALDH2 and XCYP26 show
      non-overlapping, complementary expression domains. Upon misexpression, XRALDH2 is
      found to reduce the forebrain territory and to posteriorize the molecular
      identity of midbrain and individual hindbrain rhombomeres in Xenopus embryos.
      Furthermore, ectopic XRALDH2, in combination with its substrate, all-trans
      retinal (ATR), can mimic the RA phenotype to result in microcephalic embryos.
      Taken together, our data support the notion that XRALDH2 plays an important role
      in RA homeostasis by the creation of a critical RA concentration gradient along
      the anteroposterior axis of early embryos, which is essential for proper
      patterning of the central nervous system in Xenopus.

PMID- 11231063
TI  - The circadian gene Clock is restricted to the anterior neural plate early in
      development and is regulated by the neural inducer noggin and the transcription
      factor Otx2.
AB  - The circadian cycle is a simple, universal molecular mechanism for imposing
      cyclical control on cellular processes. Here we have examined the regulation of
      one of the key circadian genes, Clock, in early Xenopus development. We find that
      the expression of Clock is dependent on developmental stage, not on time per se,
      and is mostly restricted to the anterior neural plate. It's expression can be
      induced by the secreted polypeptide noggin, and subsequently upregulated by Otx2,
      a transcription factor required for the determination of anterior fate.

PMID- 11231064
TI  - Neuroepithelial co-expression of Gbx2 and Otx2 precedes Fgf8 expression in the
      isthmic organizer.
AB  - The most studied secondary neural organizer is the isthmic organizer, which is
      localized at the mid-hindbrain transition of the neural tube and controls the
      anterior hindbrain and midbrain regionalization. Otx2 and Gbx2 expressions are
      fundamental for positioning the organizer and the establishment of molecular
      interactions that induce Fgf8. We present here evidences demonstrating that Otx2
      and Gbx2 have an overlapping expression in the isthmic region. This area is the
      transversal domain where expression of Fgf8 is induced. The Fgf8 protein produced
      in the isthmus stabilizes and up-regulates Gbx2 expression, which, in turn, down
      regulates Otx2 expression. The inductive effect of the Gbx2/Otx2 limit keeps Fgf8
      expression stable and thus maintains its positive role in the expression of Pax2,
      En1,2 and Wnt1.

PMID- 11231065
TI  - The tissue polarity gene nemo carries out multiple roles in patterning during
      Drosophila development.
AB  - Drosophila nemo was first identified as a gene required for tissue polarity
      during ommatidial development. We have extended the analysis of nemo and found
      that it participates in multiple developmental processes. It is required during
      wing development for wing shape and vein patterning. We observe genetic
      interactions between nemo and mutations in the Notch, Wingless, Frizzled and
      Decapentaplegic pathways. Our data support the findings from other organisms that
      Nemo proteins act as negative regulators of Wingless signaling. nemo mutations
      cause polarity defects in the adult wing and overexpression of nemo leads to
      abdominal polarity defects. The expression of nemo during embryogenesis is
      dynamic and dsRNA inhibition and ectopic expression studies indicate that nemo is
      essential during embryogenesis.

PMID- 11231066
TI  - Extensive tissue-specific variation of allelic methylation in the Igf2 gene
      during mouse fetal development: relation to expression and imprinting.
AB  - The imprinted Igf2 gene is active only on the paternal allele in most tissues.
      Its imprinting involves a cis-acting imprinting-control region (ICR) located
      upstream of the neighboring and maternally expressed H19 gene. It is thought that
      differential methylation of the parental alleles at the ICR is crucial for
      parental imprinting of both genes. Differentially methylated regions (DMRs) have
      also been identified within the Igf2 gene and their differential methylation is
      thought to be established during early development. To gain further insight into
      the function of these DMRs, we performed a quantitative analysis of their allelic
      methylation levels in different tissues during fetal development and the
      postnatal period in the mouse. Surprisingly, we found that the methylation levels
      of Igf2 DMRs vary extensively during fetal development, mostly on the expressed
      paternal allele. In particular, in skeletal muscle, differential allelic
      methylation in both DMR 1 and DMR 2 occurs only after birth, whereas correct
      paternal monoallelic expression is always observed, including in the embryonic
      stages. This suggests that differential methylation in the DMR 1 and DMR 2 of the
      Igf2 gene is dispensable for its imprinting in skeletal muscle. Furthermore,
      progressive methylation of the Igf2 paternal allele appears to be correlated with
      concomitant postnatal down-regulation and silencing of the gene. We discuss
      possible relations between Igf2 allelic methylation and expression during fetal
      development.

PMID- 11231067
TI  - A conserved regulatory element present in all Drosophila rhodopsin genes mediates
      Pax6 functions and participates in the fine-tuning of cell-specific expression.
AB  - The Drosophila rhodopsin genes (rh's) represent a unique family of highly
      regulated cell-specific genes, where each member has its own expression pattern
      in the visual system. Extensive analysis of the rh's has revealed several
      functional elements that are involved in cell-specificity. We have investigated
      the functional role of the RCSI/P3 site that is found in the proximal promoter of
      all Drosophila rh genes. This sequence is remarkably conserved in evolution and
      is located 15-30 bp upstream of the TATA box. We have previously shown that, in
      the context of the rh1 promoter, this element is recognized in vivo by a Pax6
      protein, the master regulator of eye development. Thus, rh regulation might
      represent the ancestral function of Pax6. Here, we investigated the role of the
      RCSI/P3 sequence in the other rh genes and show that they also mediate Pax6
      function. We also tested the potential impact of the various RCSI/P3 sequences on
      the precise cell-specific expression of rh genes. Our results demonstrate that,
      even though all RCSI/P3 sequences bind Pax6, they are clearly distinct in various
      rh promoters and these differences are conserved throughout evolution: RCSI/P3
      appears to participate in the fine-tuning of cell-specificity. We also show that
      Pax6 or a related Pax protein may be involved in the regulation of olfactory
      genes. Therefore, in addition to performing a global photoreceptor-specific
      function, RCSI also appears to mediate the combined action of Pax6 and other
      factors and to contribute to rh regulation in subsets of photoreceptors.

PMID- 11231068
TI  - Distinct roles of maf genes during Xenopus lens development.
AB  - Lens development provides a good model system for studying cellular and molecular
      mechanisms underlying embryonic induction and morphogenesis. Members of the large
      Maf family of transcription factors, L-Maf and c-Maf, have been shown to play key
      roles in chick and mouse lens development. Here we report identification of two
      Xenopus maf genes, XmafB and XL-maf, which exhibit unique temporal and spatial
      expression patterns during lens formation. XmafB can first be detected in the
      presumptive lens-forming ectoderm, when the primary eye vesicle makes contact
      with the head ectoderm. XL-maf expression appears a little later, just before
      thickening of the lens placode, and both XmafB and XL-maf can be detected in the
      lens placode. During lens vesicle formation, the expression domains of XmafB and
      XL-maf segregated from each other, resulting in restricted expression in lens
      epithelial and fiber cells, respectively. When the optic cup anlagen was removed,
      only XmafB expression is detected. Both Mafs can induce the lens fiber cell
      specific markers, betaA4- and gamma-crystallins. In animal cap assays, XmafB can
      induce Pax6, Xlens1 and Sox3 expression, but XL-maf fails to induce Pax6 and
      Xlens1 expression. These results suggest that these maf genes are involved in the
      regulation of cell-type specific gene expression and play roles in inductive
      events during Xenopus lens development.

PMID- 11231069
TI  - Misexpression of IGF-I in the mouse lens expands the transitional zone and
      perturbs lens polarization.
AB  - Insulin-like growth factor-I (IGF-I) has been implicated as a regulator of lens
      development. Experiments performed in the chick have indicated that IGF-I can
      stimulate lens fiber cell differentiation and may be involved in controlling lens
      polarization. To assess IGF-I activity on mammalian lens cells in vivo, we
      generated transgenic mice in which this factor was overexpressed from the alphaA
      crystallin promoter. Interestingly, we observed no premature differentiation of
      lens epithelial cells. The pattern of lens polarization was perturbed, with an
      apparent expansion of the epithelial compartment towards the posterior lens pole.
      The distribution of immunoreactivity for MIP26 and p57(KIP2) and a modified
      pattern of proliferation suggested that this morphological change was best
      described as an expansion of the germinative and transitional zones. The
      expression of IGF-I signaling components in the normal transitional zone and
      expansion of the transitional zone in the transgenic lens both suggest that
      endogenous IGF-I may provide a spatial cue that helps to control the normal
      location of this domain.

PMID- 11231070
TI  - The novel transcription factor gene Sp5 exhibits a dynamic and highly restricted
      expression pattern during mouse embryogenesis.
AB  - We describe the sequence and expression pattern of Sp5, a novel member of the
      vertebrate Sp1 transcription factor gene family which consists of at least five
      members. This gene family is characterized by a highly conserved domain which is
      formed by three Zn fingers, which bind to the GC box or the GT/CACC box in the
      promoter of many genes. These boxes are important cis-acting elements required
      for the expression of the respective genes. In vitro experiments indicate that
      the Sp1 transcription factors act by influencing the methylation state of the
      DNA, or by direct interactions with other promoter specific transcription
      factors. Despite intensive research, the results from in vivo experiments,
      including targeted gene inactivation, have been difficult to explain. This may be
      due to possible redundancies and interferences with other transcription factors
      of this gene family. Here, we report the isolation of the mouse Sp5 gene, a novel
      Sp1 homolog. Its sequence indicates that Sp5 is a possible link between Sp1 and
      the closely related BTEB/KLF gene family. We provide detailed information of its
      highly dynamic expression pattern during mouse embryogenesis in the developing
      brain, the spinal cord, the trigeminal ganglia, the somites and additional sites
      outside the nervous system starting from embryonic day 7.25 (E7.25) up to E10.5.

PMID- 11231071
TI  - Lbx1 marks a subset of interneurons in chick hindbrain and spinal cord.
AB  - The putative transcription factor Lbx1 is expressed in the mantle zone of the
      hindbrain and spinal cord caudal to rhombomere 1, in a specific domain of the
      alar plate. The Lbx1 domain overlaps with the expression domains for Tlx3 and
      partially with the domains for Pax2/Lim1. The ventral border of the Lbx1 domain
      coincides with the ventral border of the dorsalmost Serrate1 stripe in the
      ventricular zone. The latter borders the intermediate stripe of both Delta and
      Lunatic fringe expression. The Lbx1 domain contains differentiated interneurons
      that project into the lateral longitudinal fasciculus.

PMID- 11231072
TI  - Specific expression of the urotensin II gene in sacral motoneurons of developing
      rat spinal cord.
AB  - The neuropeptide urotensin II (UII) is expressed in motoneurons of the brainstem
      and spinal cord in adults. Here, the expression pattern of the UII gene was
      studied in the developing rat spinal cord. UII mRNA was detected by reverse
      transcription-polymerase chain reaction (RT-PCR) as early as E10. From E14 to
      E21, in situ hybridization revealed intense expression of the UII gene
      specifically in sacral motoneurons, while only faint expression was detected at
      cervical and thoracic levels. After birth (P0, P4), the expression of UII mRNA
      increased in motoneurons at all rostrocaudal levels. Thus, UII is the first gene
      reported to show expression limited to the sacral pool of motoneurons, which are
      known to have particular properties in terms of targets and programmed cell
      death.

PMID- 11231073
TI  - Expression of class 3 semaphorins and neuropilin receptors in the developing
      mouse tooth.
AB  - The semaphorins are a large family of secreted or cell-bound signals needed for
      the development of the nervous system. We compared mRNA expression of class 3
      semaphorins (Sema3A, 3B, 3C and 3F) and their two receptors (Neuropilin-1 and -2)
      in the embryonic mouse first molar tooth germ (E10-18) by radioactive in situ
      hybridization. All genes showed distinct developmentally regulated expression
      patterns during tooth organogenesis. Interestingly, Sema3A and 3C were first
      detected in the early dental epithelium, and later both genes were present in the
      epithelial primary enamel knot, a putative signaling center of the embryonic
      tooth regulating tooth morphogenesis. Prior to birth, Sema3A was also observed in
      tooth-specific cells, preodontoblasts, which later differentiate into
      odontoblasts secreting dentin, and in the mesenchymal dental follicle cells
      surrounding the tooth germ. Sema3B appeared transiently in the dental mesenchyme
      in the bud and cap stage tooth while Sema3F was expressed in both epithelial and
      mesenchymal components of the tooth. Of note, Npn-1 expression pattern was
      largely complementary to that of Sema3A, and transcripts were restricted to the
      dental mesenchymal cells. Npn-1 expression was first seen in the developing
      dental follicle, and later transcripts also appeared in the dental papilla
      mesenchyme. In contrast, Npn-2 signal was seen in both epithelial and mesenchymal
      tissues such as in the primary enamel knot and preodontoblasts.

PMID- 11231074
TI  - CEPU-1 expression in the early embryonic chick brain.
AB  - We describe the expression pattern of CEPU-1, a cell adhesion molecule of the
      immunoglobulin superfamily, in the early chick embryo brain. An initially broad
      domain of expression, encompassing forebrain, midbrain and anterior hindbrain, is
      subsequently narrowed down to a ring-shaped domain at the midbrain-hindbrain
      boundary, co-localizing precisely with the expression of Wnt1 at the isthmus. In
      addition, CEPU-1 is expressed in the dorsal aspect of rhombomere 4 and its
      emigrating neural crest cells. Later in development, we also find CEPU-1
      expression in other parts of the developing nervous system such as sensory
      ganglia and in the ventral aspect of forebrain, midbrain and hindbrain.

PMID- 11231076
TI  - A new member of the spalt like zinc finger protein family, Msal-3, is expressed
      in the CNS and sites of epithelial/mesenchymal interaction.
AB  - We have identified a new member of the spalt-like gene family in mice, msal-3. We
      compared the expression patterns of msal-3 and msal-1 during development and show
      that they exhibit overlapping yet exclusive patterns of expression in the
      developing forebrain, diencephalon, midbrain/hindbrain boundary and spinal cord.
      Both genes are expressed from E7 in opposite gradients in primitive streak
      mesoderm. Subsequently their transcripts are localized to regions of
      mesenchyme/epithelial interaction in the palate, heart, limbs, anal and
      urogenital region.

PMID- 11231075
TI  - Xath2, a bHLH gene expressed during a late transition stage of neurogenesis in
      the forebrain of Xenopus embryos.
AB  - We have identified a Xenopus bHLH gene, Xath2, which is the homologue of the
      murine MATH-2/NEX-1 gene, using a functional expression screening approach.
      Overexpression of this gene in neurula embryos induces the expression of the N
      tubulin neuronal marker but does not stimulate the expression of the X-ngnr-1 and
      NeuroD proneural genes. Expression of Xath2 begins in stage 32 embryos and is
      restricted to the dorsal telencephalon. Within the neuroepithelium of the dorsal
      telencephalon, Xath2 expression is detected in postmitotic cells located more
      laterally than those expressing several other related bHLH neuronal regulators.

PMID- 11231077
TI  - Developmentally regulated expression of Smad3, Smad4, Smad6, and Smad7 involved
      in TGF-beta signaling.
AB  - Transforming growth factor-beta (TGF-beta) signaling is mediated from
      serine/threonine kinase receptors to transcriptional responses via Smad proteins.
      Here comparison of mRNA expression of Smad3-7 in mouse embryos (E9-E15) revealed
      developmentally regulated distinct expression patterns for Smad3, 4, 6, and 7.
      Smad3 was prominently expressed in the differentiating (from E10) central nervous
      system, but also in developing bones, branchial arches and epithelium of various
      tissues. Smad4 mostly showed ubiquitous expression, but in E15 embryos, a
      pronounced signal appeared in epithelial crypts of the gut. Inhibitory Smad6 and
      Smad7 were coexpressed at high levels in developing cardiovascular system from
      the earliest stages studied. In contrast, Smad6 was selectively expressed at high
      levels, e.g. in intramembranous bone whereas Smad7 was prominent in seminiferous
      tubules of the testis, demonstrating distinct expression of these genes in non
      cardiovascular tissues.

PMID- 11231078
TI  - Regulation of laminin and COUP-TF expression in extraembryonic endodermal cells.
AB  - Laminin expression and the subsequent deposition of a basement membrane by
      primitive endoderm cells is necessary for early mammalian development. We
      demonstrate that the transcription factors COUP-TF I and II are up-regulated in
      primitive endoderm cells faster than LAMB1 and LAMC1, and that either COUP-TF is
      sufficient to induce expression of these laminin genes.

PMID- 11231079
TI  - Comparative expression analysis of the genes encoding polypyrimidine tract
      binding protein (PTB) and its neural homologue (brPTB) in prenatal and postnatal
      mouse brain.
AB  - The polypyrimidine tract binding protein (PTB) and its recently discovered
      homologue brain-enriched PTB (brPTB) are RNA binding proteins involved in the
      control of alternative splicing. We have characterized expression patterns of the
      PTB and brPTB in course of mouse brain development, using mRNA in situ
      hybridization. PTB is expressed in choroid plexi and ependyma at all the stages
      of development and temporarily in the mantle layer of migrating neuroblasts of
      fore-, mid- and hindbrain and in the external granular layer of cerebellum. In
      the neurons of adult mouse cerebrum and cerebellum expression of PTB is
      undetectable. In contrast to this, brPTB is expressed ubiquitously in neuroblasts
      of various parts of embryonic brain and in the differentiated neurons of
      postnatal cerebrum and cerebellum. brPTB mRNA is not observed in choroid plexi
      and ependymal layer. Thus, in the embryonic brain expression patterns of PTB and
      brPTB overlap, but in the course of brain development the patterns become
      complementary to each other.

PMID- 11231080
TI  - BRM (SNF2alpha) expression is concomitant to the onset of vasculogenesis in early
      mouse postimplantation development.
AB  - In mammals, the SWI/SNF complex is involved in chromatin remodelling in a wide
      range of cellular events for which regulatory factors require access to DNA. In
      the present study, we analyzed in early postimplantation mouse embryos the
      expression pattern of BRM (SNF2alpha) and BRG1 (SNF2beta), which are both ATPase
      subunits of this complex. Contrarily to the previous studies conducted in adult
      mice, showing the ubiquitous and overlapping expressions of BRM and BRG1, we show
      that BRM expression is restricted to mesodermal tissues involved in early
      vasculogenesis and heart morphogenesis.

PMID- 11231081
TI  - A correlation between versican and neurofilament expression patterns during the
      development and adult cycling of rat vibrissa follicles.
AB  - Versican, a proteoglycan recently implicated in hair follicle induction, has been
      shown to influence axon outgrowth in vitro and in vivo. We used
      immunohistochemistry to study the relationship between versican expression and
      innervation, during rat vibrissa follicle development and the adult hair cycle.
      During development, nerve fibres were commonly associated with areas of weak
      versican expression, and the path of axons appeared to be delineated by sharp
      boundaries of versican expression. Versican expression changed in the lower
      follicle dermis during the adult hair follicle cycle but remained strong around
      the follicle neck reflecting the constant innervation. Our observations show a
      correlation between versican expression and peripheral innervation indicating
      that versican may have a dual role in hair follicle biology.

PMID- 11231082
TI  - HoxA and HoxB cluster genes subdivide the digestive tract into morphological
      domains during chick development.
AB  - The digestive tract exhibits region-specific morphology and cytodifferentiation
      along the anteroposterior axis. We analyzed the spatial expression patterns of
      Hox genes belonging to the HoxA and HoxB cluster (Hoxa-4 approximately a-9, Hoxb
      5 approximately b-9) in the developing chick digestive tract. The expression
      domains of these Hox genes correlated with morphological subdivision of the
      digestive tract along the anteroposterior axis.

PMID- 11231083
TI  - Dopamine transporter expression distinguishes dopaminergic neurons from other
      catecholaminergic neurons in the developing zebrafish embryo.
AB  - To characterize the formation of the dopaminergic system in the developing
      zebrafish CNS, we cloned cDNAs encoding tyrosine hydroxylase (th), an enzyme in
      dopamine synthesis, and the dopamine transporter (dat), a membrane transport
      protein which terminates dopamine action by re-uptake. Dopaminergic neurons are
      first detected between 18 and 19 h post-fertilization in a cluster of cells in
      the ventral diencephalon. Subsequently, th and dat detection identifies
      dopaminergic neurons in the olfactory bulb, the pretectum, the retina and the
      locus coeruleus. Neurons expressing th but not dat are adrenergic or
      noradrenergic, and are found in the locus coeruleus, the medulla, the likely
      analog of the carotid body, and precursors of the enteric and sympathetic nervous
      system.

PMID- 11231084
TI  - Netrin-3 protein is localized to the axons of motor, sensory, and sympathetic
      neurons.
AB  - The netrin family of axon guidance cues has been shown to play a pivotal role in
      the guidance of a variety of axon projections during embryonic development, both
      in the vertebrate and invertebrate. While the guidance potential of netrin-1 has
      been examined in depth in many regions of the developing mouse brain very little
      information is available on the expression and activity of netrin-3. Here we show
      that the netrin-3 protein is present on motor neurons and subpopulations of
      neurons within sensory and sympathetic ganglia. Moreover, significant levels of
      netrin-3 protein were found to be associated with the axons projecting from these
      neurons suggesting a role for netrin-3 in axon pathfinding and fasciculation
      within the peripheral nervous system.

PMID- 11231085
TI  - Identification and characterization of roundabout orthologs in zebrafish.
AB  - The Roundabout (Robo) family of receptors and their extracellular ligands, the
      Slit protein family, play important roles in repulsive axon guidance. First
      identified in Drosophila, Robo receptors form an evolutionarily conserved sub
      family of the immunoglobulin (Ig) superfamily that are characterized by the
      presence of five Ig repeats and three fibronectin-type III repeats in the
      extracellular domain, a transmembrane domain, and a cytoplasmic domain with
      several conserved motifs that play important roles in Robo-mediated signaling
      (Cell 92 (1998) 205; Cell 101 (2000) 703). Robo family members have now been
      identified in C. elegans, Xenopus, rat, mouse, and human (Cell 92 (1998) 205;
      Cell 92 (1998) 217; Cell 96 (1999) 807; Dev. Biol. 207 (1999) 62). Furthermore,
      multiple robo genes have been described in Drosophila, rat, mouse and humans,
      raising the possibility of potential redundancy and diversity in robo gene
      function. As a first step in elucidating the role of Robo receptors during
      vertebrate development, we identified and characterized two Robo family members
      from zebrafish. We named these zebrafish genes robo1 and robo3, reflecting their
      amino acid sequence similarity to other vertebrate robo genes. Both genes are
      dynamically expressed in the developing nervous system in distinct patterns.
      robo3 is expressed during the first day of development in the hindbrain and
      spinal cord and is later expressed in the tectum and retina. robo1 nervous system
      expression appears later in development and is more restricted. Moreover, both
      genes are expressed in non-neuronal tissues consistent with additional roles for
      these genes during development.

PMID- 11231087
TI  - Cloning and expression of sprint, a Drosophila homologue of RIN1.
AB  - The small GTPase Ras is critical for regulation of growth and differentiation
      during development. The mammalian protein RIN1 is a potential Ras effector
      protein, which can also interact with the Abelson tyrosine kinase. However, its
      biological function is unknown. We have identified the Drosophila homologue of
      RIN1, called sprint, for SH2, poly-proline containing Ras interactor. The sprint
      locus is very large and contains at least two differentially expressed isoforms
      (sprint-a and sprint-b). Both isoforms are expressed in the ovary and maternal
      mRNA is deposited into embryos. In addition, sprint is zygotically expressed in
      the developing midgut, amnioserosa and in a specific subset of CNS neurons. The
      expression patterns of the two sprint isoforms are temporally distinct suggesting
      that the isoforms may have unique functions.

PMID- 11231086
TI  - Cell-specific patterns of Cbfa1 mRNA and protein expression in postnatal murine
      dental tissues.
AB  - Cbfa1 (core binding factor alpha 1) is a transcription factor that is a key
      determinant of the osteoblastic lineage. Recent data showed that Cbfa1 is also
      highly expressed in early stages of tooth development and is involved in crown
      morphogenesis and cytodifferentiation of odontoblasts. Here we report the mRNA
      expression and protein localization of Cbfa1 in the mouse dentition in (later)
      stages of crown and root development. In addition to osteoblasts, osteocytes,
      chondrocytes, odontoblasts, dental follicle cells, cementoblasts and periodontal
      ligament cells, we report also Cbfa1 expression in dental epithelial cells
      (secretory and maturation ameloblasts) and several non-mineralizing cell types
      (hair follicles, ducts of salivary glands, and junctional epithelium of the
      gingiva).

PMID- 11231088
TI  - Expression pattern of the drm/gremlin gene during chicken embryonic development.
AB  - The drm gene encodes a cystine knot-containing secreted and cell membrane
      associated glycoprotein shown to be an antagonist of BMPs. Drm was recently
      reported to play a crucial role in limb bud development, by its capacity to bind
      BMPs. Here, we have studied the expression pattern of drm transcripts during
      chicken development, by using whole-mount in situ hybridization. We show that,
      from stage 22HH to stage 26HH, in addition to limb buds, drm is expressed in
      cephalic neural crest-derived branchial arches I, II and III, in the medio-dorsal
      lip of the myotome and in the superficial dermatome

PMID- 11231089
TI  - Identification and expression of the mammalian homologue of Bicaudal-C.
AB  - Translational activation and repression play an important role in the spatial
      temporal regulation of gene expression in embryonic development. Bicaudal-C is an
      RNA-binding molecule believed to function at this post-transcriptional level.
      Loss-of-function mutants in Drosophila affect anterior-posterior patterning
      because of ectopic and premature translation of the posterior determinant oskar.
      The Xenopus homologue of Bicaudal-C is one of the few molecules that, when
      microinjected ectopically, results in endoderm formation in the absence of
      mesoderm induction. Here we report the sequence and expression pattern of the
      murine and human homologues of Bicaudal-C. The human gene is located on
      chromosome 10q21.2. Expression analysis in mouse using in situ hybridization
      detects expression of Bicaudal-C not only in domains detected in Xenopus, but
      also in previously unreported regions. As in Xenopus, mouse Bicaudal-C mRNA is
      found in the growing oocyte, Hensen's node, and the developing kidney.
      Additionally, at later stages it is strongly expressed in the developing gut
      endoderm, in areas of cartilage formation, in pleuro-peritoneal membrane
      derivatives, in lung mesenchyme, and in the stroma of the ovary. We conclude that
      mouse Bicaudal-C is a maternally provided gene product that is tightly regulated
      during mammalian cell differentiation.

PMID- 11231090
TI  - Molecular cloning and embryonic expression of Xenopus Six homeobox genes.
AB  - Six genes are vertebrate homologues of the homeobox-containing gene sine oculis,
      which plays an essential role in controlling Drosophila compound eye development.
      Here we report the identification and expression patterns of all three
      subfamilies of Xenopus Six genes. Two Six2 subfamily genes (Six1, Six2) showed
      very similar expression patterns in cranial ganglia, otic placodes and the eyes.
      Non-neural expression of Six1 and Six2 was observed with mesodermal head
      mesenchyme, somites and their derivatives, the muscle anlagen of the embryonic
      trunk. In addition, Six2 expression was also found with mesenchyme associated
      with the developing stomach and pronephros. Expression of Six3 subfamily genes
      (Six3.1, Six3.2, Six6.1, and Six6.2) was restricted to the developing head, where
      expression was especially observed in derivatives of the forebrain (eyes, optic
      stalks, the hypothalamus and pituitary gland). Interestingly, expression of all
      Six3 subfamily members but Six6.2 was also found with the pineal gland primordium
      and the tegmentum. Expression of Six4 subfamily genes (Six4.1, Six4.2) was
      present in the developing visceral arches, placodal derivatives (otic vesicle,
      olfactory system), head mesenchyme and the eye. The observed dynamic expression
      patterns are largely conserved between lower and higher vertebrates and imply
      important roles of Six family genes not only in eye formation and myogenesis, but
      also in the development of the gut, the kidney and of placode-derived structures.

PMID- 11231091
TI  - Expression of zebrafish Hoxa1a in neuronal cells of the midbrain and anterior
      hindbrain.
AB  - The expression pattern of zebrafish hoxa1a mRNA during embryonic development was
      studied. Herein, we show that hoxa1a mRNA is expressed in the ventral region of
      both the midbrain and anterior hindbrain during the developmental period from the
      pharyngula to the protruding-mouth stages via whole-mount in situ hybridization.
      Furthermore, double-labeling with anti-zHu antibody confirms that the zebrafish
      hoxa1a gene is expressed in neuronal cells. The observed temporal and spatial
      distributions of zebrafish hoxa1a mRNA differ greatly from the expression
      patterns of zebrafish hoxb1a and hoxb1b paralagous genes. In addition, in embryos
      injected with mouse ihh mRNA, hoxa1a-expressing cells increase in number with a
      dorsalized expression pattern in the midbrain.

PMID- 11231092
TI  - Developmentally controlled expression patterns of intermediate filament proteins
      in the cephalochordate Branchiostoma.
AB  - Expression of cytoplasmic intermediate filament (IF) proteins starts in the
      gastrula with three keratins (k1, Y1, D1) and protein X1. The number of IF
      proteins expressed increases at the neurula and early larval stages to seven and
      11, respectively, and reaches 13 in the adult. Using antibodies specific for a
      single IF protein the expression patterns of nine of the 13 IF proteins were
      analyzed at different developmental stages. Keratin k1 of the larval epidermis is
      replaced in the juvenile by keratin E1. Protein C1 of the larval epidermis
      persists only weakly and only in the most ventral part of the adult. While down
      regulated in the adult epidermis k1 and C1 are major proteins in the atrial
      epithelium which forms in the later larva. B1 is currently the only IF protein
      expressed in mesodermally derived tissues such as the muscle tails and some
      coelomic epithelia. Two-dimensional gels confirm that keratins are the major IF
      proteins in the nerve cord. Immunogold electronmicroscopy shows that proteins X1
      and C2 are present in epidermis and nerve cord in keratin IF.

PMID- 11231094
TI  - Embryonic expression patterns of the mouse and chick Gas1 genes.
AB  - Control of cell proliferation is essential to generate the defined form of a
      multi-cellular organism. While much is known about the regulators for cell cycle
      progression, relatively little is known about the state of growth arrest. Growth
      arrest (G0) is defined as a cell in a metabolically active but proliferation
      quiescent state (reviewed in Baserga (1985) The Biology of Cell Reproduction),
      typically induced by serum starvation in vitro. Using subtractive hybridization,
      Schneider et al. (Cell 54 (1988) 787) identified six genes (Gas1 through Gas6)
      whose expressions are upregulated in serum-deprived NIH3T3 cells. Among the Gas
      genes, Gas1 is the only one that can cause growth arrest when expressed in
      cultured cell (Cell 70 (1995) 595; Int. J. Cancer 9 (1998) 569). Here, we
      describe for the first time the expression pattern of Gas1 during mouse
      embryogenesis. Our data reveal that Gas1 is expressed in many regions that the
      cells are actively proliferating and suggest that it may have other roles during
      development than negatively regulating cell proliferation. Furthermore, we have
      cloned the chick GAS1 gene and documented the similarity and divergence of Gas1
      gene expression patterns between the two species.

PMID- 11231093
TI  - Dscr1, a novel endogenous inhibitor of calcineurin signaling, is expressed in the
      primitive ventricle of the heart and during neurogenesis.
AB  - We have demonstrated that DSCR1 acts as a negative regulator of calcineurin
      mediated signaling and that its transcript is overexpressed in the Down syndrome
      (DS) fetal brain. To evaluate the possible involvement of DSCR1 in DS, we have
      cloned the mouse gene and analyzed its expression pattern in the central nervous
      system (CNS). Early expression of Dscr1 is detected mainly in the heart tube and
      in the CNS in rhombomere 4 and the pretectum. From embryonic day 14.5 onwards,
      Dscr1 is widely distributed in the CNS but becomes more restricted as the brain
      matures. We confirmed its neuronal expression pattern in the adult,
      preferentially in Purkinje and pyramidal cells, by double labeling with glial
      fibrillary acidic protein. We also show that although Dscr1 is present in trisomy
      in the Ts65Dn mouse, the adult brain expression pattern is not significantly
      altered. This expression pattern indicated that Dscr1 is a developmentally
      regulated gene involved in neurogenesis and cardiogenesis and suggests that it
      may contribute to the alterations observed in these organ systems in DS patients.

PMID- 11231095
TI  - Audio-visual speech perception in schizophrenia: an fMRI study.
AB  - Abnormalities in the integration of auditory and visual language inputs could
      underlie many core psychotic features. Perceptual confusion may arise because of
      the normal propensity of visual speech perception to evoke auditory percepts.
      Recent functional neuroimaging studies of normal subjects have demonstrated
      activation in auditory-linguistic brain areas in response to silent lip-reading.
      Three functional magnetic resonance imaging experiments were carried out on seven
      normal volunteers, and 14 schizophrenia patients, half of whom were actively
      psychotic. The tasks involved listening to auditory speech, silent lip-reading
      (visual speech), and perception of meaningless lip movements (visual non-speech).
      Subjects also undertook a behavioural study of audio-visual word identification
      designed to evoke perceptual fusions. Patients and controls both showed
      susceptibility to audio-visual fusions on the behavioural task. The patient group
      as a whole showed less activation relative to controls in superior and inferior
      posterior temporal areas while performing the silent lip-reading task. Attending
      to visual non-speech, the patients activated less posterior (occipito-temporal)
      and more anterior (frontal, insular and striatal) brain areas than controls. This
      difference was accounted for largely by the psychotic subgroup. Insular and
      striatal areas were also activated in both subject groups in the auditory speech
      perception condition, thus demonstrating the bimodal sensitivity of these
      regions. The results suggest that schizophrenia patients with psychotic symptoms
      respond to visually ambiguous stimuli (non-speech) by activation of polysensory
      structures. This could reflect particular processing strategies and may increase
      susceptibility to certain paranoid and hallucinatory symptoms.

PMID- 11231096
TI  - White matter abnormalities in HIV-1 infection: a diffusion tensor imaging study.
AB  - Diffuse white matter pallor is the most frequent neuropathological feature of HIV
      1 infection and has been found to be particularly prominent in the advanced
      stages of the disease. The purpose of this study was to determine whether subtle
      white matter abnormalities can be detected in medically stable, ambulatory HIV-1
      patients, in vivo, using diffusion tensor imaging (DTI). DTI is a magnetic
      resonance imaging (MRI) technique that is uniquely suited for the study of subtle
      white matter abnormalities. DTI was performed in six HIV-1 patients and nine
      controls. The two groups were similar in age. Abnormal fractional anisotropy was
      found in the white matter of the frontal lobes and internal capsules of the HIV-1
      patients, in the absence of group differences in mean diffusivity, computed
      proton density, and computed T2. DTI may be more sensitive than conventional MRI
      methods for detecting subtle white matter disruptions in HIV-1 disease.

PMID- 11231097
TI  - A volumetric magnetic resonance imaging study of monozygotic twins discordant for
      bipolar disorder.
AB  - Six monozygotic (MZ) twin pairs discordant for bipolar disorder were compared
      with normal MZ twins with magnetic resonance imaging (MRI) on volumes of basal
      ganglia (BG), amygdala-hippocampus (AH), and cerebral hemisphere. Caudate nuclei
      were larger in both affected and unaffected bipolar twins than in normal MZ
      twins. The right hippocampus was smaller in the sick vs. well bipolar twins. The
      hippocampus was also less asymmetric in the affected bipolar twins than in the
      well cotwins and the normal MZ twins. These anatomical structures continue to be
      of interest in bipolar disorder research.

PMID- 11231098
TI  - Increased thalamic N-acetylaspartate in male patients with familial bipolar I
      disorder.
AB  - N-Acetylaspartate (NAA) in the anterior and mediodorsal thalamic regions was
      measured using proton magnetic resonance spectroscopic imaging (1H-MRSI) in 15
      euthymic male patients with familial bipolar I disorder and compared to values in
      15 male control subjects to determine if there was evidence for altered
      neuronal/axonal integrity. MRI tissue segmentation methods were also utilized to
      obtain tissue-contribution estimates for each MRSI voxel. Relative to the
      comparison group, the patients with bipolar I disorder demonstrated significantly
      higher NAA and creatine in both the right and left thalamus. NAA was also
      significantly higher in the left thalamus compared to the right in both bipolar I
      patients and controls. There were no group or lateralized differences in the
      percentages of different tissue types within the MRSI voxels, suggesting that the
      thalamic NAA and creatine alterations were not an artifact of variations in
      tissue type percentages in the MRSI voxels. There was also no significant
      association between NAA or creatine and illness duration. The findings of
      increased thalamic NAA bilaterally may represent neuronal hypertrophy or
      hyperplasia, reduced glial cell density, or abnormal synaptic and dendritic
      pruning. Increased thalamic creatine bilaterally may represent altered cellular
      energy metabolism and is consistent with prior studies demonstrating changes in
      thalamic metabolism in mood disorders.

PMID- 11231099
TI  - Menstrual cycle-related brain metabolite changes using 1H magnetic resonance
      spectroscopy in premenopausal women: a pilot study.
AB  - Proton magnetic resonance spectroscopy (1H-MRS) was used to assess neurochemical
      brain changes across the menstrual cycle in five women with premenstrual
      dysphoric disorder (PMDD) and six control subjects. Women with PMDD and control
      subjects were scanned on days 8 and 26 within one menstrual cycle (i.e. at times
      of complete absence and height of PMDD symptoms, respectively). The point
      resolved spectroscopic sequence (PRESS) was used to localize a voxel of 8 ml in
      the medial frontal gray matter and in the occipito-parietal white matter. The
      ratio of N-acetyl-aspartate to creatine in the region of the medial prefrontal
      cortex and the cingulate gyrus declined significantly from the follicular to the
      luteal phase in both groups of subjects. The menstrual phase-dependent
      significant increase in the ratio of choline to creatine was observed in the
      parietal white matter. The myo-inositol/creatine ratio exhibited a trend toward
      higher levels in the PMDD patients in the luteal phase of the menstrual cycle.
      Differences between PMDD and control subjects were not statistically significant.
      Menstrual cycle phase-dependent changes in ovarian hormonal concentrations may
      influence the neurochemistry of brain activity in premenopausal women.

PMID- 11231100
TI  - Future training needs in the pharmaceutical sciences: academia -- industry.
AB  - The markets for the traditional output of schools of pharmacy, namely education,
      research and graduates, are changing. The main private client in these markets,
      the pharmaceutical industry, is moving fast to become more efficient, under
      pressure from overly costly drug development. The challenges to the industry that
      emanate from the fantastic rate of advances in the biomedical sciences and
      pharmaceutical development are considerable. The many agents that were unheard of
      10 years ago, such as gene-regulators, together with new technologies, all
      require new approaches to fundamental pharmaceutical issues. The concept of
      disciplines in graduate education may have to be reconsidered in the light of the
      multidisciplinary problems to be tackled. In addition, graduates will need to
      acquire a range of non-disciplinary skills, such as better communication or team
      working, in order to be effective in the commercial market place. The concept of
      'research schools' following either a local or network model may provide the way
      forward to help academia meet the graduate education needs of industry. The
      objectives and mission of such institutions must be clearly defined to ensure
      that the current scientific environment is embraced fully.

PMID- 11231101
TI  - Challenges faced by the pharmaceutical industry: training graduates for
      employment in pharmaceutical R&D.
AB  - There is a shortfall between output from universities and demand by the
      pharmaceutical and health care industries for science and engineering graduates
      able to rapidly contribute to success in the business environment. Against a
      changing infrastructure of pharmaceutical research, the development of new
      chemical entities by major companies accounts for a high proportion of R&D
      expenditure. Allocation of staff is divided fairly evenly between discovery, non
      clinical and clinical research activities and in all categories the new sciences
      are likely to be used extensively. In dealing with the shortfall the challenge
      comes from balancing education in basic science with training in the emerging
      areas of science and technology. There is a need for a 'partnership' that
      includes not only industry and academia but also government, since these three
      bodies have both synergistic and diverging interests in scientific education. On
      the education-training continuum, industry should recognise what it most values
      from academia and provide as much input and support as possible. At the same time
      universities must question their ability to fulfil their traditional educational
      role in the face of current rates of adoption of new sciences and technology.
      While disciplinary excellence remains vital for PhD students, multi-disciplinary
      programmes are becoming increasingly important to enable graduates to function
      effectively in the modern, globalised pharmaceutical industry.

PMID- 11231102
TI  - Grapefruit juice enhances intestinal absorption of the P-glycoprotein substrate
      talinolol.
AB  - Grapefruit juice (GFJ) is known to affect the pharmacokinetics of various drugs,
      presumably mainly via inhibition of oxidative metabolism. In order to evaluate
      the effect of GFJ on P-glycoprotein-related transport processes, measurements of
      transport characteristics through Caco-2 monolayers and in vivo drug absorption
      studies were performed with the transported, yet not metabolized model compound
      talinolol. Apical-to-basolateral talinolol transport in the Caco-2 model at 1 mM
      racemate concentration was increased almost 3-fold when GFJ was present (S
      talinolol P(eff): 0.16 x 10(-6) vs. 0.61 x 10(-6) cm/s without vs. with GFJ; R
      talinolol P(eff): 0.19 x 10(-6) vs. 0.71 x 10(-6) cm/s without vs. with GFJ). In
      vivo in rats, doubled maximum plasma concentrations, enhanced AUC values (C(max)
      of S-talinolol: control, 77.5 ng/ml vs. GFJ, 163.6 ng/ml; C(max) of R-talinolol:
      control, 79.5 ng/ml vs. GFJ, 163.0 ng/ml; AUC of S-talinolol: control, 19.3
      microg ml(-1)min vs. GFJ, 29.9 microg ml(-1)min; AUC of R-talinolol: control,
      22.2 microg ml(-1)min vs. GFJ, 30.1 microg ml(-1)min), and decreased apparent
      oral clearances were found for both talinolol enantiomers when GFJ was
      administered together with a racemic 10 mg/kg b.w. p.o. dose. Furthermore, GFJ
      tended to accelerate the rate of talinolol input, but did not significantly
      affect terminal talinolol half-lives. It is concluded that inhibition of
      intestinal secretion may contribute to bioavailability enhancement upon GFJ
      intake.

PMID- 11231103
TI  - Cytotoxicity of novel trifluoromethylquinoline derivatives on human leukemia
      cells.
AB  - This report is a comparative study of the in vitro cell-growth inhibitory
      activity of six new trifluoromethylquinoline derivatives on human promyelocytic
      leukemic cells and the evaluation of their DNA binding characteristics. 2,8
      Bis(trifluoromethyl)quinoline-4-(N(4)-ethyl-5-nitroimidazolo)methylene ketone
      shows the highest cell-growth inhibitory activity with IC(50) of 10+/-2.5 microM,
      causes extensive changes in the morphology of the HL-60 cells and appears to
      induce apoptosis. The other compounds are only moderately growth-inhibitory,
      while 8-trifluoromethylquinoline-4-(N(4)-ethyl-5-nitroimidazolo)methylene ketone
      is actually stimulatory to cell growth. Except for the latter, the cell growth
      inhibitory activity of these compounds appears to be due their ability to bind to
      and intercalate DNA.

PMID- 11231104
TI  - Making the most of sparse clinical data by using a predictive-model-based
      analysis, illustrated with a stavudine pharmacokinetic study.
AB  - A small-scale clinical investigation was done to quantify the penetration of
      stavudine (D4T) into cerebrospinal fluid (CSF). A model-based analysis estimates
      the steady-state ratio of AUCs of CSF and plasma concentrations (R(AUC)) to be
      0.270, and the mean residence time of drug in the CSF to be 7.04 h. The analysis
      illustrates the advantages of a causal (scientific, predictive) model-based
      approach to analysis over a noncausal (empirical, descriptive) approach when the
      data, as here, demonstrate certain problematic features commonly encountered in
      clinical data, namely (i) few subjects, (ii) sparse sampling, (iii) repeated
      measures, (iv) imbalance, and (v) individual design variation. These features
      generally require special attention in data analysis. The causal-model-based
      analysis deals with features (i) and (ii), both of which reduce efficiency, by
      combining data from different studies and adding subject-matter prior
      information. It deals with features (iii)--(v), all of which prevent 'averaging'
      individual data points directly, first, by adjusting in the model for
      interindividual data differences due to design differences, secondly, by
      explicitly differentiating between interpatient, interoccasion, and measurement
      error variation, and lastly, by defining a scientifically meaningful estimand
      (R(AUC)) that is independent of design.

PMID- 11231105
TI  - Antitumor activity of benzamide riboside and its combination with cisplatin and
      staurosporine.
AB  - Benzamide riboside (BR), a new synthetic nucleoside analogue, has demonstrated a
      potent cytotoxic activity in murine leukemia in vitro. The purpose of the present
      investigation was to examine the antitumor activity of BR in mice bearing
      leukemia L1210. The results revealed that BR possesses a potent antitumor
      activity in vivo. It increases life-span of mice with leukemia. Synergistic
      cytotoxicity of BR with select DNA damaging agents, cisplatin (cis-Pt) and
      staurosporine (STP) was examined in MTT chemosensitivity assay, FACS analyses and
      apoptotic DNA fragmentation on L1210 cells in culture. A simultaneous treatment
      of leukemia L1210 cells with the combination of BR and STP resulted in
      synergistic cytotoxicity that correlated with increased apoptotic activity in
      those cells. On the other hand, treatment of L1210 cells with combination of BR
      and cis-Pt resulted in antagonistic cytotoxic effect. Finally, to elucidate the
      synergistic effect of BR and STP in inducing apoptosis, the attention was
      directed to the activation of cell death processes through various cell cycle
      signals. This is the first report describing in vivo antitumor activity of BR and
      its utilization in combination chemotherapy.

PMID- 11231106
TI  - Interactions between carbamazepine and polyethylene glycol (PEG) 6000:
      characterisations of the physical, solid dispersed and eutectic mixtures.
AB  - The influence of a hydrophilic carrier (PEG 6000) on the polymorphism of
      carbamazepine, an antiepileptic drug, was investigated in binary physical
      mixtures and solid dispersions by means of differential scanning calorimetry
      (DSC), thermal gravimetry, hot-stage microscopy (HSM), and X-ray diffractometry,
      respectively. This study provides also an attempt to develop a method to
      calculate more precisely the eutectic composition. In rather ideal physical
      mixtures, carbamazepine was found as monoclinic Form III. In solid dispersions,
      the drug was found to crystallize as trigonal Form II; a eutectic invariant in
      the PEG 6000-rich composition domain (6% of carbamazepine mass) was evidenced by
      DSC experiments and confirmed by HSM observations. In the binary phase diagram
      the ideal carbamazepine liquidus curve was located at temperatures higher than
      the respective experimental ones. This suggests that drug can be maintained in
      the liquid state in the temperature-mass fraction (T--x) region between the two
      carbamazepine liquidus curves. This indicates in turn that attractive
      interactions occur between carbamazepine and PEG 6000-chains. These interactions
      have been also claimed to prevent carbamazepine from degradation into
      iminostilbene (a compound resulting from the chemical degradation of
      carbamazepine which is postulated to be responsible for the idiosyncratic
      toxicity of the drug) and thought to lead to the crystallization of metastable
      Carbamazepine II from melt. The negative excess entropy for eutectic mixtures
      indicated that the drug crystals are finely dispersed in the bulk of polymer
      chains.

PMID- 11231107
TI  - Pretreatment with potent P-glycoprotein ligands may increase intestinal secretion
      in rats.
AB  - The expression of P-glycoprotein is induced in cell cultures upon exposure to
      various inducers. Therefore, the aim of the present study was to evaluate the in
      vivo relevance of this observation, i.e. the influence of chronic pretreatments
      with selected drugs -- all of which are ligands to P-glycoprotein (P-gp) as
      demonstrated in radioligand binding studies and all of which have some or a
      considerable effect on P-gp expression in Caco-2 cells -- on the effective
      intestinal permeabilities of the model compound talinolol in rats employing in
      situ single-pass intestinal perfusion of three different gut segments. Talinolol
      was selected, because it shows high selectivity for one of the exsorptive
      transporters (P-gp) and its intestinal permeability is very sensitive to changes
      in exsorption when the perfusate concentration is low. Prior to the induction
      study the perfusion model was optimized regarding the type and concentration of a
      competitive inhibitor which may be used to block the exsorption-related
      permeability reduction (through intestinal exsorption) during an ongoing
      perfusion and would permit an intra-individual comparison of the effective
      permeability without and with blockade of exsorption. While repetitive verapamil
      and talinolol dosing had no statistically significant exsorption-inducing effect,
      vinblastine and rifampicin pretreatments resulted in decreased intestinal
      talinolol permeabilities in the three tested gut segments, duodenum, jejunum, and
      colon [e.g., S-talinolol in jejunum: control, 2.50 x 10(-4) cm/s; vinblastine
      induction, 1.48 x 10(-4) cm/s (P<0.05); rifampicin induction, 1.51 x 10(-4) cm/s
      (P<0.05)]. Addition of an efficient secretion inhibitor (vinblastine) to the
      perfusate permitted the determination of the impact of inhibitable secretory
      processes on the total effective permeabilities and an estimation of passive
      permeability in the respective individual. The inhibitable permeability fractions
      were higher for vinblastine than for any other pretreatment and the difference
      from control pretreatment was statistically significant for all intestinal
      segments (duodenum, 61.8%; jejunum, 63.1%; colon, 43,7%; S-talinolol).
      Statistically significant differences were also detected for rifampicin in the
      perfused duodenum and jejunum (33.1 and 27.5% increase in inhibitable fraction,
      respectively, for S-talinolol). These differences are explained by a significant
      induction of outside-directed transport in the intestinal enterocytes by
      vinblastine and rifampicin.

PMID- 11231108
TI  - A statistical design to evaluate the influence of manufacturing factors on the
      material properties and functionalities of microcrystalline cellulose.
AB  - The aim of this study is to statistically evaluate the effects of manufacturing
      factors on the material properties and functionalities of microcrystalline
      cellulose (MCC) products. How the material properties of MCC products dominate
      their functionalities was further explored. Results demonstrate that the desired
      material properties and functionalities of MCC products can be obtained by
      manipulation of the manufacturing factors using proper polynomial equations, and
      the key manufacturing factor is temperature. On the other hand, the
      functionalities can be quantitatively predicted by material properties.
      Meanwhile, the key material property is molecular mass in controlling MCC
      functionalities. The particle morphologies may also serve as important material
      properties. In conclusion, the careful control of temperature during the
      manufacture of MCC might minimize inter-batch variation. The correlation of the
      material properties of MCC products with their functionalities might help the
      formulation designer rationally select proper MCC products. The universal
      harmonization of MCC products might be achieved by the regulation of their
      molecular mass, surface roughness, and roundness.

PMID- 11231109
TI  - Chromatographic retention of drug molecules on immobilised liposomes prepared
      from egg phospholipids and from chemically pure phospholipids.
AB  - The partitioning of a chemically diverse set of drugs into liposomes was studied
      by immobilised liposome chromatography (ILC). For this purpose liposomes composed
      of (i) purified egg phospholipids (EPL), (ii) synthetic phosphatidylcholine (PC),
      (iii) PC--synthetic phosphatidylethanolamine (PE) 80:20 (mol/mol) and (iv) PC-
      synthetic phosphatidylserine (PS) 80:20 (mol/mol) were immobilised in gel beads
      by freeze-thawing. The drug partitioning was assessed from the retention volume,
      which was expressed as a capacity factor, K(s), normalised with respect to the
      amount of immobilised phospholipid. The drug retention on EPL, PC and PC--PE
      liposomes was very similar, whereas the negatively charged PC--PS liposomes
      increased the retention of positively charged and decreased retention of
      negatively charged drugs. The partitioning of drugs on liposome columns (log
      K(s)) versus their octanol--water partitioning (log P(oct)) showed three separate
      rectilinear relationships, depending on the charge of the compound (neutral,
      positive, or negative). Statistical analysis (ANCOVA) proved that the lines had
      similar slopes. Repeated analysis of four reference compounds showed a low
      variation (<0.12 log units) over time (about 250 days). A close relationship was
      observed between the drug retention in short EPL columns with a low content of
      phospholipids and the retention in longer standard EPL columns. The short 'quick
      screen bilayer columns' permit analysis of highly lipophilic compounds within 30
      min and are thus applicable for medium-throughput screening in drug discovery
      settings. A very strong rectilinear relationship (r(2)=0.95, n=13) between log
      K(s) (EPL) and published liposome partitioning data (log D(mem)) confirmed that
      the ILC drug retention reflects the drug partitioning into the lipid bilayers. A
      moderate to fair rectilinear relationship was observed between the normalised
      retention on PC, PC-PE and EPL liposomes (r(2)=0.79, 0.86 and 0.85, respectively,
      n=24) and corresponding published log k'(IAM) data obtained on immobilised
      artificial membrane (IAM) columns. Transport across Caco-2 cell monolayers (log
      P(c)) showed curvilinear relationships with log K(s), log k'(IAM), log P(oct) and
      log D(oct). The drug fraction absorbed in humans showed a similar relationship to
      log K(s) values as to surface plasmon resonance signals representing drug
      liposome interaction (Danelian et al., 2000 J Med Chem, 43, 2083--2086).

PMID- 11231110
TI  - Computational modelling of inhibitor binding to human thrombin.
AB  - Thrombin is an essential protein involved in blood clot formation and an
      important clinical target, since disturbances of the coagulation process cause
      serious cardiovascular diseases such as thrombosis. Here we evaluate the
      performance of a molecular dynamics based method for predicting the binding
      affinities of different types of human thrombin inhibitors. For a series of eight
      ligands the method ranks their relative affinities reasonably well. The binding
      free energy difference between high and low affinity representatives in the test
      set is quantitatively reproduced, as well as the stereospecificity for a chiral
      inhibitor. The original parametrisation of this linear interaction energy method
      requires the addition of a constant energy term in the case of thrombin. This
      yields a mean unsigned error of 0.68 kcal/mol for the absolute binding free
      energies. This type of approach is also useful for elucidating three-dimensional
      structure-activity relationships in terms of microscopic interactions of the
      ligands with the solvated enzyme.

PMID- 11231111
TI  - High-throughput cytochrome P450 (CYP) inhibition screening via a cassette probe
      dosing strategy. V. Validation of a direct injection/on-line guard cartridge
      extraction--tandem mass spectrometry method for CYP1A2 inhibition assessment.
AB  - An efficient direct injection/on-line guard cartridge extraction-tandem mass
      spectrometry (DI/GCE--MS--MS) method has been validated for high-throughput
      evaluation of cytochrome P450 (CYP) 1A2 inhibition potential using human hepatic
      microsomes and 96-well microtiter plates. Microsomal incubations were terminated
      with formic acid, centrifuged, and the resulting supernatants were injected for
      DI/GCE--MS--MS analysis. Due to the use of an extremely short C(18) guard
      cartridge, this method offers several advantages such as no sample preparation,
      excellent on-line extraction, short run time and minimal source contamination and
      performance deterioration. The DI/GCE--MS--MS method demonstrates acceptable
      accuracy and precision for the quantification of resorufin, a marker metabolite
      of ethoxyresorufin mediated by CYP1A2, in microsomal incubations. The inhibition
      potential of CYP1A2 has been evaluated using its selective inhibitors, alpha
      naphthoflavone and furafylline. The IC(50) values (120 nM for alpha
      naphthoflavone and 5.1 microM for furafylline) measured by the new method are in
      agreement with the literature values.

PMID- 11231112
TI  - Estimation of the percolation thresholds in dextromethorphan hydrobromide
      matrices.
AB  - Percolation theory is a multidisciplinary theory that studies chaotic systems. It
      has been applied in the pharmaceutical field since 1987. Knowledge of the
      percolation threshold -- one of the most important concepts in percolation theory
      -- results in a clear improvement of the solid dosage form design. The
      percolation threshold is the concentration showing the maximum probability to
      obtain, for the first time, a percolating cluster of a substance. In this work,
      the percolation thresholds of dextromethorphan.HBr/Eudragit RS-PM inert matrices
      were estimated. The drug percolation threshold was estimated as 0.3691+/-0.0541
      (P=0.05) of the total porosity (ranging between 23 and 36% w/w of drug). The SEM
      micrographs of the matrices are consistent with the estimated percolation range.
      In agreement with previous reports, different percolation thresholds were found
      for the matrix forming excipient Eudragit RS-PM. The site percolation threshold
      (based on the release properties) ranged between 10 and 20% v/v of the excipient,
      the site-bond percolation threshold (estimated from the mechanical properties)
      between 29.5 and 34% v/v of the excipient and the swelling percolation threshold
      between 34.3 and 46.9% v/v of the excipient. These percolation ranges are in
      agreement with those found previously for Eudragit RS-PM matrices containing
      naltrexone.HCl and morphine.HCl.

PMID- 11231113
TI  - New sorbent for HPTLC--FTIR in situ determination of impurities in flurazepam.
AB  - An efficient HPTLC--UV/FTIR coupling procedure is presented for the separation
      and rapid identification of flurazepam hydrochloride and its related substances
      in bulk powder and capsules. An optimized mobile phase was developed for the
      separation on specialized plates for HPTLC--FTIR in situ measurement containing a
      proportion of 50% magnesium tungstate. The proposed procedure shows several
      advantages to the related compound test of the pharmacopoeia, e.g. baseline
      separation of the known impurities and detection of the substances as peaks in
      the UV, Gram-Schmidt or window chromatograms. Furthermore, unambiguous
      identification is obtained by postrun extraction of the DRIFT spectra and
      comparison with reference spectra in the library. Quantification of the related
      compounds was carried out densitometrically. This method shows that the current
      resurgence of interest in modern instrumental TLC is rightful based on the
      flexibility and efficiency of this analytical method.

PMID- 11231115
TI  - Characterization of chitosan hydrochloride--mucin rheological interaction:
      influence of polymer concentration and polymer:mucin weight ratio.
AB  - The aim of the present work was to investigate the influence of polymer
      concentration and polymer:mucin weight ratio on chitosan--mucin interaction,
      assessed by means of viscosimetric measurements. Two hydration media, distilled
      water and 0.1 M HCl, were used. Chitosan solutions were prepared at
      concentrations greater than the characteristic entanglement concentration and
      mixed with increasing amounts of porcine gastric mucin. Viscosity measurements
      were performed on the polymer--mucin mixtures and on polymer and mucin solutions
      having the same concentrations as in the mixtures. The flow curves were fitted
      according to a modified form of Cheng--Evans equation in order to obtain the
      relevant model parameters: low shear viscosity eta(0) and high shear viscosity
      eta(infinity), indexes of the sample structure at rest and upon high shear,
      respectively. The formation of chitosan--mucin interaction products was
      determined on the basis of the changes in eta(0) and eta(infinity) of the
      mixtures as a function of polymer:mucin weight ratio. Rheological synergism
      parameter was also calculated. The results obtained suggest that two different
      types of rheological interaction occur between chitosan and mucin in both media,
      depending on polymer concentration and polymer:mucin weight ratio: one is
      characterized by a minimum in viscosity and occurs at higher polymer:mucin weight
      ratio, the other one produces a positive rheological synergism and is observed in
      presence of an excess of mucin. Only the last one causes a 'strengthening' of the
      mucoadhesive interface and it is responsible for the mucoadhesive joint. This
      hypothesis is confirmed by tensile stress measurements performed on HCS solutions
      in presence of mucin dispersions at different concentrations.

PMID- 11231114
TI  - Cyclosporine-loaded polycaprolactone nanoparticles: immunosuppression and
      nephrotoxicity in rats.
AB  - AIM: The nephrotoxicity and immunosuppressive ability of cyclosporine (CyA)
      incorporated into polycaprolactone nanoparticles (CyA-NP) was assessed in vitro
      and in vivo and compared to the effects caused by free drug (Sandimmun. METHODS:
      The in vivo study included four groups (12 Wistar rats each) receiving oral CyA
      (10 mg/kg/day for 3 days) as an emulsion of Sandimmun in whole milk or CyA-NP and
      equivalent doses of empty NP or cremophor in milk as controls. CyA concentrations
      in blood, urine, liver, spleen and kidney at 24 h post-dosing were measured by
      fluorescence polarization immunoassay (FPIA). The nephrotoxicity induced by each
      drug treatment was determined by measuring creatinine plasma levels, malonyl
      dialdehyde production, and H(2)O(2) and reduced glutathione contents in
      glomeruli. On the other hand, the immunosuppressive effect was estimated in vivo
      by incubating lymphocyte suspensions obtained from CyA-, CyA-NP- and control
      treated rats, as well as in vitro on lymphocyte suspensions from non-treated
      healthy animals. RESULTS: Significantly higher blood, urine and tissue levels
      were achieved with CyA-NP compared to free CyA. However, no changes in creatinine
      plasma levels were detected due to either CyA or CyA-NP treatment. Only the
      production of H(2)O(2) in the glomeruli exhibited a significant increase as
      compared to control groups, but no differences could be ascribed to the different
      drug treatments. In vivo, the immunosuppressive activity was also comparable for
      both drug treatments. In contrast, CyA-NP showed a better drug uptake in vitro at
      concentrations above 25 microM. No immunosuppression was detected in control
      groups. CONCLUSION: NP improve the oral bioavailability of CyA and its uptake by
      lymphocytes in vitro above 25 microM. On the contrary, specific immunosuppression
      and adverse effects were not simultaneously increased. Further studies are needed
      to clarify the results.

PMID- 11231116
TI  - Mitomycin antitumor compounds. Part 1. CD studies on their molecular structure.
AB  - The UV-Vis and circular dichroism (CD) spectra of several mitomycin antitumor
      compounds and some of their derivatives were analyzed in order to attribute the
      proper assignment to their electronic transitions. The lowest energy pi-->pi*
      transition was found to depend on the effect of the auxochromic group in the
      aromatic ring, whereas the three n-->pi* transitions, present at around 240, 400
      and 560 nm, are related to the C(9)==O of the carbamoyl group and to the C(8)==O
      and the C(5)==O of the quinone, respectively. The chirality of the C(9) is
      responsible for the sign of the Cotton effect (CE) at around 240 nm, whereas the
      substituents of the chromophore for mitosane derivatives and the conformation of
      the carbamoyloxymethyl group at C(9) determine the CE sign of the (1)A-->(1)L(b)
      transition. When the aziridine ring was opened and mitosenes derivatives were
      obtained, CD spectra did not differ significantly among the compounds and the
      bands associated to the different transitions had similar Cotton effect. Our
      findings suggest that the differences in the CD spectra, observed between
      mitosanes and mitosenes, are probably related to the more rigid molecular
      structure of the mitosene derivatives and the different conformations in solution
      of the C(9) side chain.

PMID- 11231117
TI  - Studies on the photostability and in vitro phototoxicity of Labetalol.
AB  - The purpose of this study was to obtain information on the photochemical and
      phototoxic properties of Labetalol, a beta-blocker drug. Preliminary information
      on the drug photoreactivity was achieved using a flow system with a photochemical
      reactor on-line with a diode array detection system. Photophysical and
      photochemical investigations on the drug were performed in aqueous solutions at
      different pH values using spectrophotometric and fluorimetric methods; the
      photodegradation quantum yield was found to be 2.7 x 10(-3) at pH 5.8 and 1.5 x
      10(-2) at pH 11.5. Forced photodegradation of labetalol solutions under exposure
      to UVA--UVB radiations (xenon arc lamp) was monitored by reversed-phase liquid
      chromatography. The main photodegradation products were isolated and
      characterized by NMR and mass spectrometry; labetalol was found to give 3-amino-1
      phenylbutane and salicylamide-4-carboxaldehyde as the main photoproducts.
      Preliminary phototoxic testings on human keratinocyte cultures were performed
      evaluating the viability of the cells by the neutral-red uptake assay; mutagenic
      and photomutagenicity tests were also carried out based on Salmonella typhimurium
      strains. As a result, labetalol was found to be photolabile,mainly in alkaline
      medium, but evidences of significant phototoxic and photomutagenic effects by the
      drug were not observed.

PMID- 11231118
TI  - Inhibitory effects of CYP3A4 substrates and their metabolites on P-glycoprotein
      mediated transport.
AB  - It is generally known that the substrates and/or inhibitors of cytochrome P450
      (CYP) 3A4 and P-glycoprotein (P-gp) overlap with each other. In intestinal
      epithelial cells, it is surmised that the metabolites coexist with their parent
      drug. However, most studies on P-gp did not take the effects of those metabolites
      into consideration. Therefore, in the present study, we investigated the
      inhibitory effects of five substrates of CYP3A4 (nifedipine, testosterone,
      midazolam, amiodarone, and azelastine) and their metabolites on the P-gp-mediated
      transcellular transport. The transcellular transports of [(3)H]daunorubicin or
      [(3)H]digoxin by monolayers of LLC-GA5-COL150 cells in which P-gp was
      overexpressed were measured in the presence or absence of the CYP3A4 substrates
      and their metabolites. Nifedipine, testosterone, midazolam, and their metabolites
      exhibited no effects on the P-gp-mediated transport of [(3)H]daunorubicin and
      [(3)H]digoxin. On the other hand, the transport of [(3)H]daunorubicin was
      strongly inhibited by amiodarone, desethylamiodarone, azelastine, and
      desmethylazelastine, with IC(50) values of 22.5, 15.4, 16.0 and 11.8 microM,
      respectively. The transport of [(3)H]digoxin was also strongly inhibited by these
      compounds, with IC(50) values of 45.6, 25.2, 30.0 and 41.8 microM, respectively.
      Another metabolite of azelastine, 6-hydroxyazelastine, exhibited no effects on
      these transports. It was suggested that the CYP3A4 metabolites of which their
      parent drug exhibited inhibition on the P-gp-mediated transport are possibly also
      inhibitors. It would be possible more complicated drug-drug interactions would be
      caused by the metabolites as well as their parent drugs in the liver and the
      intestine via the inhibition of CYP3A4 and P-gp.

PMID- 11231119
TI  - The development of an instrumented tamp-filling capsule machine II.
      Investigations of plug development and tamping pressure at different filling
      stations.
AB  - A previously described [Eur. J. Pharm. Sci. 10 (2000) 267] pneumatic tamping head
      with attached instrumentation, capable of recording tamping forces generated on a
      Bosch GKF tamp-filling machine with high precision was employed to investigate
      the development and density of plugs during capsule tamp-filling of two soft,
      ductile powders. The study aimed to make a contribution to control capsule fill
      weight by monitoring the tamping force. The results indicated that the tamping
      station utilised to measure the tamping force and that involved in the regulation
      of the pressure of the pneumatic chamber of the tamping head should preferably
      not be the same. A possible solution would be to install the instrumented
      pneumatic tamping head on tamping station 4, after which in all cases plugs had
      formed to their maximum length and density. A second pneumatic tamping head,
      without instrumentation, could be installed on tamping station 3, which would
      receive signals from the instrumentation, and as a result the inner chamber
      pressure of this second pneumatic tamping head could be changed to adjust fill
      weight. The cumulative tamping distance should be large enough to produce a force
      reading well above the limit set by the inner chamber pressure, but small enough
      to avoid overfilling of the capsules. The latter can be detected monitoring the
      variability of the tamping forces recorded. A larger standard deviation of the
      tamping forces obtained from tamping station 4 was found to be a strong indicator
      of overfilling.

PMID- 11231121
TI  - Function and regulation of ATP-binding cassette transport proteins involved in
      hepatobiliary transport.
AB  - Hepatobiliary transport of endogenous and exogenous compounds is mediated by the
      coordinated action of multiple transport systems present at the sinusoidal
      (basolateral) and canalicular (apical) membrane domains of hepatocytes. During
      the last few years many of these transporters have been cloned and functionally
      characterized. In addition, the molecular bases of several forms of cholestatic
      liver disease have been defined. Combined, this has greatly expanded our
      understanding of the normal physiology of bile formation, the pathophysiology of
      intrahepatic cholestasis, as well as of drug elimination and disposition
      processes. In this review recent advances, with respect to function and
      regulation of ATP binding cassette transport proteins expressed in liver, are
      summarized and discussed.

PMID- 11231122
TI  - The molecular basis of nuclear genetic code change in ciliates.
AB  - BACKGROUND: The nuclear genetic code has changed in several lineages of ciliates.
      These changes, UAR to glutamine and UGA to cysteine, imply that eukaryotic
      release factor 1 (eRF1), the protein that recognizes stop codons and terminates
      translation, changes specificity. Here we test whether changes in eRF1 drive
      genetic code evolution. RESULTS: Database sequence analysis reveals numerous
      genetic code alterations in ciliates, including UGA --> tryptophan in Blepharisma
      americanum and the distantly related Colpoda. We sequenced eRF1 from four
      ciliates: B. americanum, a heterotrich that independently derived the same eRF1
      specificity as Euplotes, and three spirotrichs, Stylonychia lemnae, S. mytilus,
      and Oxytricha trifallax, that independently derived the same genetic code as
      Tetrahymena (UAR --> glutamine). Distantly related ciliates with similar codes
      show characteristic changes in eRF1. We used a sliding window analysis to test
      associations between changes in specific eRF1 residues and changes in the genetic
      code. The regions of eRF1 that display convergent substitutions are identical to
      those identified in a recently reported nonsense suppression mutant screen in
      yeast. CONCLUSIONS: Genetic code change by stop codon reassignment is
      surprisingly frequent in ciliates, with UGA --> tryptophan occurring twice
      independently. This is the first description of this code, previously found only
      in bacteria and mitochondria, in a eukaryotic nuclear genome. eRF1 has evolved
      strikingly convergently in lineages with variant genetic codes. The strong
      concordance with biochemical data indicates that our methodology may be generally
      useful for detecting molecular determinants of biochemical changes in evolution.

PMID- 11231123
TI  - Drosophila par-1 is required for oocyte differentiation and microtubule
      organization.
AB  - BACKGROUND: Drosophila oocyte determination involves a complex process by which a
      single cell within an interconnected cyst of 16 germline cells differentiates
      into an oocyte. This process requires the asymmetric accumulation of both
      specific messenger RNAs and proteins within the future oocyte as well as the
      proper organization of the microtubule cytoskeleton, which together with the
      fusome provides polarity within the developing germline cyst. RESULTS: In
      addition to its previously described late oogenic role in the establishment of
      anterior-posterior polarity and subsequent embryonic axis formation, the
      Drosophila par-1 gene is required very early in the germline for establishing
      cyst polarity and for oocyte specification. Germline clonal analyses, for which
      we used a protein null mutation, reveal that Drosophila par-1 (par-1) is required
      for the asymmetric accumulation of oocyte-specific factors as well as the proper
      organization of the microtubule cytoskeleton. Similarly, somatic clonal analyses
      indicate that par-1 is required for microtubule stabilization in follicle cells.
      The PAR-1 protein is localized to the fusome and ring canals within the
      developing germline cyst in direct contact with microtubules. Likewise, in the
      follicular epithelium, PAR-1 colocalizes with microtubules along the basolateral
      membrane. However, in either case PAR-1 localization is independent of
      microtubules. CONCLUSIONS: The Drosophila par-1 gene plays at least two essential
      roles during oogenesis; it is required early in the germline for organization of
      the microtubule cytoskeleton and subsequent oocyte determination, and it has a
      second, previously described role late in oogenesis in axis formation. In both
      cases, par-1 appears to exert its effects through the regulation of microtubule
      dynamics and/or stability, and this finding is consistent with the defined role
      of the mammalian PAR-1 homologs.

PMID- 11231124
TI  - B-type cyclins CLB5 and CLB6 control the initiation of recombination and
      synaptonemal complex formation in yeast meiosis.
AB  - BACKGROUND: The life cycle of most eukaryotic organisms includes a meiotic phase,
      in which diploid parental cells produce haploid gametes. During meiosis a single
      round of DNA replication is followed by two rounds of chromosome segregation. In
      the first, or reductional, division (meiosis I), which is unique to meiotic
      cells, homologous chromosomes segregate from one another, whereas in the second,
      or equational, division (Meiosis II) sister centromeres disjoin. Meiotic DNA
      replication precedes the initiation of recombination by programmed Spo11
      dependent DNA double-strand breaks. Recent reports that meiosis-specific cohesion
      is established during meiotic S phase and that the length of S phase is modified
      by recombination factors (Spo11 and Rec8) raise the possibility that replication
      plays a fundamental role in the recombination process. RESULTS: To address how
      replication influences the initiation of recombination, we have used mutations in
      the B-type cyclin genes CLB5 and CLB6, which specifically prevent premeiotic
      replication in the yeast Saccharomyces cerevisiae. We find that clb5 and clb5
      clb6 but not clb6 mutants are defective in DSB induction and prior associated
      changes in chromatin accessibility, heteroallelic recombination, and SC
      formation. The severity of these phenotypes in each mutant reflects the extent of
      replication impairment. CONCLUSIONS: This assemblage of phenotypes reveals roles
      for CLB5 and CLB6 not only in DNA replication but also in other key events of
      meiotic prophase. Links between the function of CLB5 and CLB6 in activating
      meiotic DNA replication and their effects on subsequent events are discussed.

PMID- 11231125
TI  - enok encodes a Drosophila putative histone acetyltransferase required for
      mushroom body neuroblast proliferation.
AB  - Mushroom bodies in the Drosophila brain are centers for olfactory learning and
      memory. We have previously shown that the mushroom bodies comprise three types of
      neurons with distinct axonal projections. These three types of neurons are
      generated sequentially from common neuroblasts. We report here the identification
      of a gene that we have named enoki mushroom (enok), which when it is mutated
      gives rise to mushroom bodies with reduced axonal structures. enok encodes a
      putative histone acetyltransferase (HAT) of the MYST family, members of which
      have been implicated as important modulators of transcriptional activity. A
      single amino acid change in the zinc finger motif of the putative catalytic HAT
      domain gives the same phenotype as a null allele, and this finding indicates the
      importance of HAT activity to Enok's function. Further phenotypic analysis
      demonstrates that the mushroom body defect is due to an arrest in neuroblast
      proliferation rather than a failure of either cell fate switching or axon
      branching. Clonal analyses in the wing discs and the ovaries suggest that enok is
      essential for normal cell proliferation in some, but not all, tissues. Our
      results provide in vivo evidence for essential functions of a histone
      acetyltransferase in the construction of the Drosophila brain.

PMID- 11231126
TI  - Targeted disruption of the Nijmegen breakage syndrome gene NBS1 leads to early
      embryonic lethality in mice.
AB  - Nijmegen breakage syndrome (NBS) is a rare autosomal recessive human disease
      whose clinical features include growth retardation, immunodeficiency, and
      increased susceptibility to lymphoid malignancies. Cells from NBS patients
      exhibit gamma-irradiation sensitivity, S-phase checkpoint defects, and genomic
      instability. Recently, it was demonstrated that this chromosomal breakage
      syndrome is caused by mutations in the NBS1 gene that result in a total loss of
      full-length NBS1 expression. Here we report that in contrast to the viability of
      NBS patients, targeted inactivation of NBS1 in mice leads to early embryonic
      lethality in utero and is associated with poorly developed embryonic and
      extraembryonic tissues. Mutant blastocysts showed greatly diminished expansion of
      the inner cell mass in culture, and this finding suggests that NBS1 mediates
      essential functions during proliferation in the absence of externally induced
      damage. Together, our results indicate that the complex phenotypes observed in
      NBS patients and cell lines may not result from a complete inactivation of NBS1
      but may instead result from hypomorphic truncation mutations compatible with cell
      viability.

PMID- 11231127
TI  - Self assembly of the transmembrane domain promotes signal transduction through
      the erythropoietin receptor.
AB  - Hematopoietic cytokine receptors, such as the erythropoietin receptor (EpoR), are
      single membrane-spanning proteins. Signal transduction through EpoR is crucial
      for the formation of mature erythrocytes. Structural evidence shows that in the
      unliganded form EpoR exists as a preformed homodimer in an open scissor-like
      conformation precluding the activation of signaling. In contrast to the
      extracellular domain of the growth hormone receptor (GHR), the structure of the
      agonist-bound EpoR extracellular region shows only minimal contacts between the
      membrane-proximal regions. This evidence suggests that the domains facilitating
      receptor dimerization may differ between cytokine receptors. We show that the
      EpoR transmembrane domain (TM) has a strong potential to self interact in a
      bacterial reporter system. Abolishing self assembly of the EpoR TM by a double
      point mutation (Leu 240-Leu 241 mutated to Gly-Pro) impairs signal transduction
      by EpoR in hematopoietic cells and the formation of erythroid colonies upon
      reconstitution in erythroid progenitor cells from EpoR(-/-) mice. Interestingly,
      inhibiting TM self assembly in the constitutively active mutant EpoR R129C
      abrogates formation of disulfide-linked receptor homodimers and consequently
      results in the loss of ligand-independent signal transduction. Thus, efficient
      signal transduction through EpoR and possibly other preformed receptor oligomers
      may be determined by the dynamics of TM self assembly.

PMID- 11231128
TI  - Zygotic development without functional mitotic centrosomes.
AB  - The centrosome is the dominant microtubule-organizing center in animal cells. At
      the onset of mitosis, each cell normally has two centrosomes that lie on opposite
      sides of the nucleus. Centrosomes nucleate the growth of microtubules and
      orchestrate the efficient assembly of the mitotic spindle. Recent studies in vivo
      and in vitro have shown that the spindle can form even in the absence of
      centrosomes and demonstrate that individual cells can divide without this
      organelle. However, since centrosomes are involved in multiple processes in vivo,
      including polarized cell divisions, which are an essential developmental
      mechanism for producing differentiated cell types, it remains to be shown whether
      or not a complete organism can develop without centrosomes. Here we show that in
      Drosophila a centrosomin (cnn) null mutant, which fails to assemble fully
      functional mitotic centrosomes and has few or no detectable astral microtubules,
      can develop into an adult fly. These results challenge long-held assumptions that
      the centrosome and the astral microtubules emanating from it are essential for
      development and are required specifically for spindle orientation during
      asymmetric cell divisions.

PMID- 11231129
TI  - Galpha(13) mediates activation of a depolarizing chloride current that
      accompanies RhoA activation in both neuronal and nonneuronal cells.
AB  - Loss of membrane potential (membrane depolarization) is one of the earliest and
      most striking responses of quiescent cells to stimulation with serum or G protein
      coupled receptor (GPCR) agonists such as lysophosphatidic acid and thrombin.
      Membrane depolarization is due to the activation of a chloride conductance. While
      this response has received relatively little attention in the past, it is clear
      that the acute loss of membrane potential may have important physiological
      consequences. However, the dissection of the underlying G protein pathway and the
      establishment of cause-effect relationships have remained elusive to date. Here
      we report that, in neuronal cells, the depolarizing chloride current invariably
      accompanies GPCR-induced activation of RhoA and subsequent neurite retraction,
      and neither of these events requires phosphoinositide hydrolysis or Ca2+
      mobilization. Through antibody microinjections and a genetic approach, we
      demonstrate that activation of the chloride conductance is mediated by Galpha(13)
      in a RhoA-independent manner in both neuronal cells and fibroblasts. We further
      show that, in neuronal cells, this newly described Galpha(13) pathway may
      profoundly modulate membrane excitability during RhoA-regulated neurite
      remodeling.

PMID- 11231130
TI  - SGS1 is required for telomere elongation in the absence of telomerase.
AB  - In S. cerevisiae, mutations in genes that encode telomerase components, such as
      the genes EST1, EST2, EST3, and TLC1, result in the loss of telomerase activity
      in vivo. Two telomerase-independent mechanisms can overcome the resulting
      senescence. Type I survival is characterized by amplification of the subtelomeric
      Y' elements with a short telomere repeat tract at the terminus. Type II survivors
      arise through the abrupt addition of long tracts of telomere repeats. Both
      mechanisms are dependent on RAD52 and on either RAD50 or RAD51. We show here that
      the telomere elongation pathway in yeast (type II) is dependent on SGS1, the
      yeast homolog of the gene products of Werner's (WRN) and Bloom's (BLM) syndromes.
      Survival in the absence of SGS1 and EST2 is dependent upon RAD52 and RAD51 but
      not RAD50. We propose that the RecQ family helicases are required for processing
      a DNA structure specific to eroding telomeres.

PMID- 11231131
TI  - Dendritic organization of actin comet tails.
AB  - Polymerization of actin filaments is necessary for both protrusion of the leading
      edge of crawling cells and propulsion of certain intracellular pathogens, and it
      is sufficient for generating force for bacterial motility in vitro. Motile
      intracellular pathogens are associated with actin-rich comet tails containing
      many of the same molecular components present in lamellipodia, and this suggests
      that these two systems use a similar mechanism for motility. However, available
      structural evidence suggests that the organization of comet tails differs from
      that of lamellipodia. Actin filaments in lamellipodia form branched arrays, which
      are thought to arise by dendritic nucleation mediated by the Arp2/3 complex. In
      contrast, comet tails have been variously described as consisting of short,
      randomly oriented filaments, with a higher degree of alignment at the periphery,
      or as containing long, straight axial filaments with a small number of oblique
      filaments. Because the assembly of pathogen-associated comet tails has been used
      as a model system for lamellipodial protrusion, it is important to resolve this
      apparent discrepancy. Here, using a platinum replica approach, we show that actin
      filament arrays in comet tails in fact have a dendritic organization with the
      Arp2/3 complex localizing to Y-junctions as in lamellipodia. Thus, comet tails
      and lamellipodia appear to share a common dendritic nucleation mechanism for
      protrusive motility. However, comet tails differ from lamellipodia in that their
      actin filaments are usually twisted and appear to be under significant torsional
      stress.

PMID- 11231132
TI  - Dominant-negative mutant dynein allows spontaneous centrosome assembly, uncouples
      chromosome and centrosome cycles.
AB  - Cleavage cycles commence and chromosome and centrosome cycles proceed in harmony
      following fertilization of Drosophila eggs and completion of the meiotic
      divisions. The sperm-introduced centrioles replicate, separate, and while recruit
      pericentriolar material centrosomes (CS) form. The CS nucleate asters of
      microtubules (MT). Spindles form following interaction of some astral MT with
      kinetochores. In unfertilized eggs, chromosomes do not replicate, and CS and MT
      asters never form, although their components are present in the egg cytoplasm;
      unknown mechanisms prevent chromosome replication and CS and MT assembly. In
      unfertilized Laborc(D) eggs, rudimentary CS assemble spontaneously and
      instantaneously and nucleate small MT asters. In fertilized Laborc(D) eggs,
      normal CS form and organize normal asters. However, the CS replicate prior to
      accomplishment of the first mitosis, and spindles with multiple CS develop. In
      fertilized Laborc(D) eggs, while the chromosome cycles cease, CS cycles proceed
      as in wild type. Knowing that Laborc(D) is a dominant-negative mutation and
      encodes the formation of mutant cytoplasmic dynein heavy chain molecules, we show
      here that cytoplasmic dynein is involved in prevention of CS assembly in
      unfertilized eggs and establishing harmony between the chromosome and the CS
      cycles.

PMID- 11231134
TI  - Lessons from the human embryo debate.
AB  - Britain has given the green light for research on stem cells derived from human
      embryos. Nigel Williams reports on the discussion ahead of this controversial
      decision.

PMID- 11231135
TI  - France pushes for greater public participation in research.
AB  - French scientists look set for greater public scrutiny if measures proposed at a
      recent meeting are carried out, writes Kenneth Lee.

PMID- 11231137
TI  - Getting precious seed on hold.

PMID- 11231138
TI  - A strategy for mapping bicoid on the phylogenetic tree.

PMID- 11231136
TI  - The win-win potential for motherhood and science.
AB  - Women wishing to combine children with a research career should not be seen as
      taking a backstep but as bolstering both activities, argues Marlene Belfort.

PMID- 11231139
TI  - Meiotic recombination: Making and breaking go hand in hand.
AB  - Accurate segregation of homologous chromosomes at the first meiotic division
      requires the tight coordination of DNA replication, homologous recombination and
      chromosome organization. Recent studies suggest that the initiation of meiotic
      recombination is mechanistically coupled to premeiotic DNA replication.

PMID- 11231140
TI  - Clathrin uncoating: Auxilin comes to life.
AB  - The DnaJ protein auxilin has been extensively studied in vitro as a cofactor for
      uncoating clathrin-coated vesicles by the chaperone Hsc70. Recent studies provide
      the first evidence that auxilin plays this role in vivo, and work on a new
      mammalian auxilin suggests the protein may have more complex cellular functions.

PMID- 11231141
TI  - Pathogen evolution: How good bacteria go bad.
AB  - Recent findings suggest that dysentery-causing Shigella strains have arisen
      several times from Escherichia coli via plasmid acquisition and phenotypic
      convergence. Similarly, three Bacillus strains with distinct pathogenic
      properties are derivatives of a single species whose behavior is profoundly
      altered by acquired plasmids.

PMID- 11231142
TI  - Cortical plasticity: It's all the range!
AB  - When rats learn a motor skill, synaptic potentials in the motor cortex are
      enhanced. A new study has revealed that this learning-induced enhancement limits
      further synaptic potentiation, but not synaptic depression. These findings
      support the view that activity-dependent synaptic plasticity is the brain's
      memory mechanism.

PMID- 11231143
TI  - Myelin: Delivery by raft.
AB  - Recent results suggest that membrane proteins are delivered to the myelin sheath
      of an oligodendrocyte on rafts with a distinctive lipid composition. The major
      intrinsic membrane protein of myelin, proteolipid protein, interacts with rafts
      in oligodendrocytes but not with the different rafts found in other cell types.

PMID- 11231144
TI  - Molecular evolution: Please release me, genetic code.
AB  - The genetic code is no longer universal, even in non-mitochondrial genomes.
      Recent studies have implicated the eukaryotic release factor eRF1 in mediating
      coding changes that are not as inconceivable as once thought. Specific residues
      in eRF1 proteins can be correlated with specific code changes in a wide variety
      of taxa.

PMID- 11231145
TI  - Mitochondrial division: New partners in membrane pinching.
AB  - Mitochondrial division is a complex process requiring the synergistic actions of
      multiple factors, including mechanical enzymes and accessory proteins. Recent
      studies have identified a number of these factors and started to elucidate how
      they act together to bring about mitochondrial fission.

PMID- 11231146
TI  - Membrane proteins: Aquaporins--channels without ions.
AB  - Recently determined structures have shed new light on the way that aquaporins act
      as passive, but selective, pores for the transport of small molecules--such as
      water or glycerol--across membranes.

PMID- 11231147
TI  - Evolution: A complement for evolutionary genetics.
AB  - Developmental geneticists' contribution to the study of the evolution of
      morphological divergence has proceeded along two lines: comparative analysis of
      gene expression and quantitative genetics. Recent studies highlight how
      complementation tests between species can bridge the gap between these
      approaches.

PMID- 11231148
TI  - Bub1 is activated by the protein kinase p90(Rsk) during Xenopus oocyte
      maturation.
AB  - BACKGROUND: The kinetochore attachment (spindle assembly) checkpoint arrests
      cells in metaphase to prevent exit from mitosis until all the chromosomes are
      aligned properly at the metaphase plate. The checkpoint operates by preventing
      activation of the anaphase-promoting complex (APC), which triggers anaphase by
      degrading mitotic cyclins and other proteins. This checkpoint is active during
      normal mitosis and upon experimental disruption of the mitotic spindle. In yeast,
      the serine/threonine protein kinase Bub1 and the WD-repeat protein Bub3 are
      elements of a signal transduction cascade that regulates the kinetochore
      attachment checkpoint. In mammalian cells, activated MAPK is present on
      kinetochores during mitosis and activity is upregulated by the spindle assembly
      checkpoint. In vertebrate unfertilized eggs, a special form of meiotic metaphase
      arrest by cytostatic factor (CSF) is mediated by MAPK activation of the protein
      kinase p90(Rsk), which leads to inhibition of the APC. However, it is not known
      whether CSF-dependent metaphase arrest caused by p90(Rsk) involves components of
      the spindle assembly checkpoint. RESULTS: xBub1 is present in resting oocytes and
      its protein level increases slightly during oocyte maturation and early
      embryogenesis. In Xenopus oocytes, Bub1 is localized to kinetochores during both
      meiosis I and meiosis II, and the electrophoretic mobility of Bub1 upon SDS-PAGE
      decreases during meiosis I, reflecting phosphorylation and activation of the
      enzyme. The activation of Bub1 can be induced in interphase egg extracts by
      selective stimulation of the MAPK pathway by c-Mos, a MAPKKK. In oocytes treated
      with the MEK1 inhibitor U0126, the MAPK pathway does not become activated, and
      Bub1 remains in its low-activity, unshifted form. Injection of a constitutively
      active target of MAPK, the protein kinase p90(Rsk), restores the activation of
      Bub1 in the presence of U0126. Moreover, purified p90(Rsk) phosphorylates Bub1 in
      vitro and increases its protein kinase activity. CONCLUSIONS: Bub1, an upstream
      component of the kinetochore attachment checkpoint, is activated during meiosis
      in Xenopus in a MAPK-dependent manner. Moreover, a single substrate of MAPK,
      p90(Rsk), is sufficient to activate Bub1 in vitro and in vivo. These results
      indicate that in vertebrate eggs, kinetochore attachment/spindle assembly
      checkpoint proteins, including Bub1, are downstream of p90(Rsk) and may be
      effectors of APC inhibition and CSF-dependent metaphase arrest by p90(Rsk).

PMID- 11231149
TI  - The cyclin-dependent kinase inhibitor Roughex is involved in mitotic exit in
      Drosophila.
AB  - BACKGROUND: Exit from mitosis is a tightly regulated event. This process has been
      studied in greatest detail in budding yeast, where several activities have been
      identified that cooperate to downregulate activity of the cyclin-dependent kinase
      (CDK) Cdc28 and force an exit from mitosis. Cdc28 is inactivated through
      proteolysis of B-type cyclins by the multisubunit ubiquitin ligase termed the
      anaphase promoting complex/cyclosome (APC/C) and inhibition by the cyclin
      dependent kinase inhibitor (CKI) Sic1. In contrast, the only mechanism known to
      be essential for CDK inactivation during mitosis in higher eukaryotes is cyclin
      destruction. RESULTS: We now present evidence that the Drosophila CKI Roughex
      (Rux) contributes to exit from mitosis. Observations of fixed and living embryos
      show that metaphase is significantly longer in rux mutants than in wild-type
      embryos. In addition, Rux overexpression is sufficient to drive cells
      experimentally arrested in metaphase into interphase. Furthermore, rux mutant
      embryos are impaired in their ability to overcome a transient metaphase arrest
      induced by expression of a stable cyclin A. Rux has numerous functional
      similarities with Sic1. While these proteins share no sequence similarity, we
      show that Sic1 inhibits mitotic Cdk1-cyclin complexes from Drosophila in vitro
      and in vivo. CONCLUSIONS: Rux inhibits Cdk1-cyclin A kinase activity during
      metaphase, thereby contributing to exit from mitosis. To our knowledge, this is
      the first mitotic function ascribed to a CKI in a multicellular organism and
      indicates the existence of a novel regulatory mechanism for the metaphase to
      anaphase transition during development.

PMID- 11231150
TI  - CLH-3, a ClC-2 anion channel ortholog activated during meiotic maturation in C.
      elegans oocytes.
AB  - BACKGROUND: ClC anion channels are ubiquitous and have been identified in
      organisms as diverse as bacteria and humans. Despite their widespread expression
      and likely physiological importance, the function and regulation of most ClCs are
      obscure. The nematode Caenorhabditis elegans offers significant experimental
      advantages for defining ClC biology. These advantages include a fully sequenced
      genome, cellular and molecular manipulability, and genetic tractability. RESULTS:
      We show by patch clamp electrophysiology that C. elegans oocytes express a
      hyperpolarization- and swelling-activated Cl(-) current with biophysical
      characteristics strongly resembling those of mammalian ClC-2. Double-stranded RNA
      mediated gene interference (RNAi) and single-oocyte RT-PCR demonstrated that the
      channel is encoded by clh-3, one of six C. elegans ClC genes. CLH-3 is inactive
      in immature oocytes but can be triggered by cell swelling. However, CLH-3 plays
      no apparent role in oocyte volume homeostasis. The physiological signal for
      channel activation is the induction of oocyte meiotic maturation. During meiotic
      maturation, the contractile activity of gonadal sheath cells, which surround
      oocytes and are coupled to them via gap junctions, increases dramatically. These
      ovulatory sheath cell contractions are initiated prematurely in animals in which
      CLH-3 expression is disrupted by RNAi. CONCLUSIONS: The inwardly rectifying Cl(-)
      current in C. elegans oocytes is due to the activity of a ClC channel encoded by
      clh-3. Functional and structural similarities suggest that CLH-3 and mammalian
      ClC-2 are orthologs. CLH-3 is activated during oocyte meiotic maturation and
      functions in part to modulate ovulatory contractions of gap junction-coupled
      gonadal sheath cells.

PMID- 11231151
TI  - Large-scale analysis of gene function in Caenorhabditis elegans by high
      throughput RNAi.
AB  - Genome-wide analysis of gene function is essential for the post-genome era, and
      development of efficient and economical technology suitable for it has been in
      demand. Here we report a large-scale inactivation of the expressed genes in the
      nematode Caenorhabditis elegans. For this purpose, we have established a high
      throughput "RNAi-by-soaking" methodology by modifying the conventional RNAi
      method [1, 2]. A set of tag-sequenced, nonredundant cDNAs corresponding to
      approximately 10,000 genes [3] (representing half of the predicted genes [4]) was
      used for the systematic RNAi analysis. We have processed approximately 2500 genes
      to date. In development, 27% of them showed detectable phenotypes, such as
      embryonic lethality, post-embryonic lethality, sterility, and morphological
      abnormality. Of these, we analyzed the phenotypes of F1 sterility in detail, and
      we have identified 24 genes that might play important roles in germline
      development. Combined with the ongoing analysis of expression patterns of these
      cDNAs [3, 5], the functional information obtained in this work will provide a
      starting point for the further analysis of each gene. Another finding from this
      screening is that the incidence of essential genes is significantly lower in the
      X chromosome than in the autosomes.

PMID- 11231152
TI  - The dissociation between perception and action in the Ebbinghaus illusion:
      nonillusory effects of pictorial cues on grasp.
AB  - According to a recently proposed distinction [1] between vision for perception
      and vision for action, visually guided movements should be largely immune to the
      perceptually compelling changes in size produced by pictorial illusions. Tests of
      this prediction that use the Ebbinghaus illusion have revealed only small effects
      of the illusion on grasp scaling as compared to its effect on perception [2-4].
      Nevertheless, some have argued that the small effect on grasp implies that there
      is a single representation of size for both perception and action [5]. Recent
      findings, however, suggest that the 2-D pictorial elements, such as those
      comprising illusory backgrounds, can sometimes be treated as obstacles and
      thereby influence the programming of grasp [6]. The arrangement of the 2-D
      elements commonly used in previous studies examining the Ebbinghaus illusion
      could therefore give rise to an effect on grasp scaling that is independent of
      its effect on perceptual judgements, even though the two effects are in the same
      direction. We present evidence demonstrating that when the gap between the target
      and the illusion-making elements in the Ebbinghaus illusion is equidistant across
      different perceptual conditions (Figure 1a), the apparent effect of the illusion
      on grasp scaling is eliminated.

PMID- 11231153
TI  - Conversion of leaves into petals in Arabidopsis.
AB  - More than 200 years ago, Goethe proposed that each of the distinct flower organs
      represents a modified leaf [1]. Support for this hypothesis has come from genetic
      studies, which have identified genes required for flower organ identity. These
      genes have been incorporated into the widely accepted ABC model of flower organ
      identity, a model that appears generally applicable to distantly related eudicots
      as well as monocot plants. Strikingly, triple mutants lacking the ABC activities
      produce leaves in place of flower organs, and this finding demonstrates that
      these genes are required for floral organ identity [2]. However, the ABC genes
      are not sufficient for floral organ identity since ectopic expression of these
      genes failed to convert vegetative leaves into flower organs. This finding
      suggests that one or more additional factors are required [3, 4]. We have
      recently shown that SEPALLATA (SEP) represents a new class of floral organ
      identity genes since the loss of SEP activity results in all flower organs
      developing as sepals [5]. Here we show that the combined action of the SEP genes,
      together with the A and B genes, is sufficient to convert leaves into petals.

PMID- 11231154
TI  - Persistent interactions between the two transmembrane clusters dictate the
      targeting and functional assembly of adenylyl cyclase.
AB  - Adenylyl cyclases possess complex structures like those of the ATP binding
      cassette (ABC) transporter family, which includes the cystic fibrosis
      transmembrane regulator, the P-glycoprotein, and ATP-sensitive K(+) channels [1
      4]. These structures comprise a cytosolic N terminus followed by two tandem six
      transmembrane cassettes, each associated with a highly homologous (ATP binding)
      cytosolic loop [5-8]. The catalytic domains, which are located in the two large
      cytoplasmic loops, are highly conserved and well studied. The crystal structure
      of these domains has even been described recently [9, 10]. However, nothing is
      known of the function or organization of the 12 transmembrane segments. In the
      present study we adopted a range of strategies including live-cell fluorescence
      resonance energy transfer (FRET) microscopy, coimmunoprecipitation, and
      functional assays of various truncated and substituted, fluorescently-tagged
      molecules to analyze the trafficking and activity of this molecule. When
      expressed as individual peptides, the two transmembrane domains - largely
      independently of any cytosolic region - formed a tight complex that was delivered
      to the plasma membrane. This cooperation between the two intact transmembrane
      domains was essential and sufficient to target the enzyme to the plasma membrane
      of the cell. The extracellular loop between the ninth and tenth transmembrane
      segments, which contains an N-glycosylation site, was also necessary.
      Furthermore, the interaction between the two transmembrane clusters played a
      critical role in bringing together the cytosolic catalytic domains to express
      functional adenylyl cyclase activity in the intact cell.

PMID- 11231155
TI  - Synthetic lethality between mutation in Atm and DNA-PK(cs) during murine
      embryogenesis.
AB  - The gene product mutated in ataxia telangiectasia, ATM, is a ubiquitously
      expressed 370 kDa protein kinase that is a key mediator of the cellular response
      to DNA damage [1]. ATM-deficient cells are radiosensitive and show impaired cell
      cycle arrest and increased chromosome breaks in response to ionizing radiation.
      ATM is a member of the phosphatidylinositol-3-kinase (PI3K)-related protein
      kinase superfamily, which includes the catalytic subunit of DNA-dependent protein
      kinase (DNA-PK(cs)) and ATR [2]. DNA-PK is a 470 kDa protein kinase that is
      required for proper end-to-end rejoining of DNA double-strand breaks [3].
      Prkdc(scid/scid) mice have a homozygous mutation in the gene encoding DNA-PK(cs)
      and, like Atm(-/-) mice, are viable and radiosensitive [4-8]. To determine if Atm
      and DNA-PK(cs) show genetic interaction, we attempted to generate mice deficient
      in both gene products. However, no scid/scid Atm(-/-) pups were recovered from
      scid/scid Atm(+/-) intercrosses. Developmental arrest of scid/scid Atm(-/-)
      embryos occurred around E7.5, a developmental stage when embryonic cells are
      hypersensitive to DNA damage [9]. This reveals synthetic lethality between
      mutations in Atm and DNA-PK and suggests that Atm and DNA-PK have complementary
      functions that are essential for development.

PMID- 11231157
TI  - Ancient DNA analysis reveals divergence of the cave bear, Ursus spelaeus, and
      brown bear, Ursus arctos, lineages.
AB  - The cave bear, Ursus spelaeus, represents one of the most frequently found
      paleontological remains from the Pleistocene in Europe. The species has always
      been confined to Europe and was contemporary with the brown bear, Ursus arctos.
      Relationships between the cave bear and the two lineages of brown bears defined
      in Europe, as well as the origins of the two species, remain controversial,
      mainly due to the wide morphological diversity of the fossil remains, which makes
      interpretation difficult [1, 2]. Sequence analysis of ancient DNA is a useful
      tool for resolving such problems because it provides an independent source of
      data [3]. We previously amplified a short DNA fragment of the mitochondrial DNA
      control region (mt control region) of a 40,000-year-old Ursus spelaeus sample
      [4]. In this paper, we describe the DNA analysis of two mtDNA regions, the
      control region and the cytochrome b gene. Control region sequences were obtained
      from ten samples of cave bears ranging from 130,000 to 20,000 years BP, and one
      particularly well-conserved sample gave a complete cyt b sequence. Our data
      demonstrate that cave bears split largely before the lineages of brown bears
      around 1.2 million years ago. Given its abundance, its wide distribution in space
      and time, and its large morphological diversity, the cave bear is a promising
      model for direct observation of the evolution of sequences throughout time,
      extinction periods, and the differentiation of populations shaped by climatic
      fluctuations during the Pleistocene.

PMID- 11231156
TI  - Requirement for Rho GTPases and PI 3-kinases during apoptotic cell phagocytosis
      by macrophages.
AB  - In vivo, apoptotic cells are removed by surrounding phagocytes, a process thought
      to be essential for tissue remodeling and the resolution of inflammation [1].
      Although apoptotic cells are known to be efficiently phagocytosed by macrophages,
      the mechanisms whereby their interaction with the phagocytes triggers their
      engulfment have not been described in mammals. Here, we report that primary
      murine bone marrow-derived macrophages (using alpha(v)beta(3) integrin for
      apoptotic cell uptake) extend lamellipodia to engulf apoptotic cells and form an
      actin cup where phosphotyrosine accumulates. Rho GTPases and PI 3-kinases have
      been widely implicated in the regulation of the actin cytoskeleton [2, 3]. We
      show that inhibition of Rho GTPases by Clostridium difficile toxin B prevents
      apoptotic cell phagocytosis and inhibits the accumulation of both F-actin and
      phosphotyrosine. Importantly, the Rho GTPases Rac1 and Cdc42 are required for
      apoptotic cell uptake whereas Rho inhibition enhances uptake. The PI 3-kinase
      inhibitor LY294002 also prevents apoptotic cell phagocytosis but has no effect on
      the accumulation of F actin and phosphotyrosine. These results indicate that both
      Rho GTPases and PI 3-kinases are involved in apoptotic cell phagocytosis but that
      they play distinct roles in this process.

PMID- 11231158
TI  - Cell mixing between the embryonic midbrain and hindbrain.
AB  - Segmentation is a mechanism that controls spatial organization along the
      anteroposterior axis of the neural tube and is particularly well characterized
      for the hindbrain region [1]. The generation of distinct and regionally specific
      structures from each rhombomere is achieved with the almost complete absence of
      cell mixing between neighboring rhombomeres [2, 3]. Here, we have examined cell
      mingling at the isthmus, where Otx2-expressing midbrain cells abut Gbx2
      expressing hindbrain cells [4]. The sharp line of demarcation between the two
      expression domains suggests that this interface would be a compartment boundary,
      with no intermixing of cells, but this has not been directly tested. We have used
      short-term reaggregation assays to compare the adhesive properties of cells
      derived from midbrain and anterior hindbrain and cell labeling in vivo directly
      to monitor cell behavior at the midbrain/hindbrain boundary. Interestingly, our
      data demonstrate that, in contrast to the rhombomeres, differential adhesion does
      not seem to operate between the midbrain and anterior hindbrain and that cells
      move between the two territories. We conclude that these two subdivisions are not
      maintained by cell lineage restriction but by cells maintaining labile fates.

PMID- 11231159
TI  - Roles of Ran-GTP and Ran-GDP in precursor vesicle recruitment and fusion during
      nuclear envelope assembly in a human cell-free system.
AB  - The molecular mechanism of nuclear envelope (NE) assembly is poorly understood,
      but in a cell-free system made from Xenopus eggs NE assembly is controlled by the
      small GTPase Ran [1,2]. In this system, Sepharose beads coated with Ran induce
      the formation of functional NEs in the absence of chromatin [1]. Both generation
      of Ran-GTP by the guanine nucleotide exchange factor RCC1 and GTP hydrolysis by
      Ran are required for NE assembly, although the roles of the GDP- and GTP-bound
      forms of Ran in the recruitment of precursor vesicles and their fusion have been
      unclear. We now show that beads coated with either Ran-GDP or Ran-GTP assemble
      functional nuclear envelopes in a cell-free system derived from mitotic human
      cells, forming pseudo-nuclei that actively transport proteins across the NE. Both
      RCC1 and the GTPase-activating protein RanGAP1 are recruited to the beads,
      allowing interconversion between Ran-GDP and Ran-GTP. However, addition of
      antibodies to RCC1 and RanGAP1 shows that Ran-GDP must be converted to Ran-GTP by
      RCC1 before precursor vesicles are recruited, whereas GTP hydrolysis by Ran
      stimulated by RanGAP1 promotes vesicle recruitment and is necessary for vesicle
      fusion to form an intact envelope. Thus, the GTP-GDP cycle of Ran controls both
      the recruitment of vesicles and their fusion to form NEs.

PMID- 11231160
TI  - Twists and turns in protein folding.

PMID- 11231161
TI  - Little green primates.

PMID- 11231162
TI  - Mendel's demon.

PMID- 11231163
TI  - Flower development.

PMID- 11231164
TI  - Functional genomics: the worm scores a knockout.
AB  - Following the completion of the genome sequence of Caenorhabditis elegans, four
      independent studies have now assessed the functions of more than a third of the
      worm's genes by analysing the phenotypes caused when each of a large set of genes
      is inactivated by RNA interference.

PMID- 11231165
TI  - mRNA quality control: Marking the message for life or death.
AB  - A protein complex deposited upstream of exon-exon junctions after pre-mRNA
      splicing may serve a dual role in mRNA quality control by directing mRNA nuclear
      export and, possibly, serving as a downstream 'mark' for nonsense-mediated decay.

PMID- 11231166
TI  - Plant physiology: the ups and downs of guard cell signalling.
AB  - How is specificity encoded in calcium-based signal transduction systems? Recent
      evidence shows that oscillations in the cytosolic free calcium concentration of
      guard cells are necessary for stimulus-specific stomatal closure in plants.

PMID- 11231167
TI  - Early visual cortex: smarter than you think.
AB  - A recent study has provided elegant evidence that the early visual area V2 plays
      an important role in image segmentation, piecing together parts of an object with
      the help of stereoscopic clues.

PMID- 11231168
TI  - Gene silencing: fleshing out the bones.
AB  - Genetic studies are revealing the pathway for RNA-mediated gene silencing. Short
      RNA molecules are the key, giving sequence specificity for RNA degradation and
      mediating communication within and between cells; these short RNAs are common to
      transcriptional and post-transcriptional silencing pathways.

PMID- 11231169
TI  - Bacterial conjugation: running rings around DNA.
AB  - Helicases are active in many aspects of DNA replication, recombination, repair
      and transcription. An integral membrane bacterial protein assembly involved in
      the transfer of DNA between cells has been shown to resemble a ring helicase,
      suggesting that it hydrolyzes ATP to pump DNA through a central channel.

PMID- 11231170
TI  - Evolution: the evolvability enigma.
AB  - A report that a switch of a yeast protein to a 'prion' state triggers diverse
      phenotypic changes has prompted re-examination of the processes of evolution. To
      what extent should processes of gene expression and control be interpreted in
      terms of their capacity to allow future evolution as well as present adaptation?

PMID- 11231171
TI  - Membrane transport: retromer to the rescue.
AB  - Genetic analysis in yeast has led to the discovery of a complex that retrieves
      proteins selectively from the prevacuolar compartment and transports them to the
      Golgi. Orthologs of these proteins in mammalian cells are likely to play a
      similar role but their cargoes are yet to be identified.

PMID- 11231172
TI  - Arabidopsis genome: life without notch.
AB  - The complete genome sequence of the flowering plant Arabidopsis thaliana has been
      determined. New insights have come from comparisons between this sequence and
      genome sequences of other species, including those of cyanobacteria, yeast, worms
      and flies.

PMID- 11231173
TI  - Towards inference of human brain connectivity from MR diffusion tensor data.
AB  - This paper describes a method to infer the connectivity induced by white matter
      fibers in the living human brain. This method stems from magnetic resonance
      tensor imaging (DTI), a technique which gives access to fiber orientations. Given
      typical DTI spatial resolution, connectivity is addressed at the level of
      fascicles made up by a bunch of parallel fibers. We propose first an algorithm
      dedicated to fascicle tracking in a direction map inferred from diffusion data.
      This algorithm takes into account fan-shaped fascicle forks usual in actual white
      matter organization. Then, we propose a method of inferring a regularized
      direction map from diffusion data in order to improve the robustness of the
      tracking. The regularization stems from an analogy between white matter
      organization and spaghetti plates. Finally, we propose a study of the tracking
      behavior according to the weight given to the regularization and some examples of
      the tracking results with in vivo human brain data.

PMID- 11231175
TI  - Extracting parametric images from dynamic contrast-enhanced MRI studies of the
      brain using factor analysis.
AB  - Factor analysis of dynamic studies (FADS) is a technique that allows structures
      with different temporal characteristics to be extracted from dynamic contrast
      enhanced studies without making any a priori assumptions about physiology. These
      dynamic structures may correspond to different tissue types or different organs
      or they may simply be a useful way of characterising the data. This paper
      describes a method of automatically extracting factor images and curves from
      contrast enhanced MRI studies of the brain. This method has been applied to 107
      studies carried out on patients with acute stroke. The results show that FADS is
      able to extract factor curves correlated to arterial and venous signal intensity
      curves and that the corresponding factor images allow a distinction to be made
      between areas of the brain with normal and abnormal perfusion. The method is
      robust and can be applied routinely to dynamic studies of the brain. The
      constraints described are sufficiently general to be applicable to other dynamic
      MRI contrast enhanced studies where an increase in contrast concentration
      produces an increase in signal intensity.

PMID- 11231174
TI  - Estimation of 3D left ventricular deformation from echocardiography.
AB  - The quantitative estimation of regional cardiac deformation from 3D image
      sequences has important clinical implications for the assessment of viability in
      the heart wall. Such estimates have so far been obtained almost exclusively from
      Magnetic Resonance (MR) images, specifically MR tagging. In this paper we
      describe a methodology for estimating cardiac deformations from 3D
      echocardiography (3DE). The images are segmented interactively and then initial
      correspondence is established using a shape-tracking approach. A dense motion
      field is then estimated using a transversely isotropic linear elastic model,
      which accounts for the fiber directions in the left ventricle. The dense motion
      field is in turn used to calculate the deformation of the heart wall in terms of
      strain in cardiac specific directions. The strains obtained using this approach
      in open-chest dogs before and after coronary occlusion, show good agreement with
      previously published results in the literature. They also exhibit a high
      correlation with strains produced in the same animals using implanted
      sonomicrometers. This proposed method provides quantitative regional 3D estimates
      of heart deformation from ultrasound images.

PMID- 11231176
TI  - 3D ultrasound measurement of large organ volume.
AB  - Freehand 3D ultrasound is particularly appropriate for the measurement of organ
      volumes. For small organs, which can be fully examined with a single sweep of the
      ultrasound probe, the results are known to be much more accurate than those using
      conventional 2D ultrasound. However, large or complex shaped organs are difficult
      to quantify in this manner because multiple sweeps are required to cover the
      entire organ. Typically, there are significant registration errors between the
      various sweeps, which generate artifacts in an interpolated voxel array, making
      segmentation of the organ very difficult. This paper describes how sequential
      freehand 3D ultrasound, which does not employ an interpolated voxel array, can be
      used to measure the volume of large organs. Partial organ cross-sections can be
      segmented in the original B-scans, and then combined, without the need for image
      based registration, to give the organ volume. The inherent accuracy (not
      including position sensor and segmentation errors) is demonstrated in simulation
      to be within +/- 2%. The in vivo precision of the complete system is demonstrated
      (by repeated observations of a human liver) to be +/- 5%.

PMID- 11231177
TI  - On the number of clusters and the fuzziness index for unsupervised FCA
      application to BOLD fMRI time series.
AB  - The aim of this paper is to present an exploratory data-driven strategy based on
      Unsupervised Fuzzy Clustering Analysis (UFCA) and its potential for fMRI data
      analysis in the temporal domain. The a priori definition of the number of
      clusters is addressed and solved using heuristics. An original validity criterion
      is proposed taking into account data geometry and the partition Membership
      Functions (MFs). From our simulations, this criterion is shown to outperform
      other indices used in the literature. The influence of the fuzziness index was
      studied using simulated activation combined with real life noise data acquired
      from subjects under a resting state. Receiver Operating Characteristics (ROC)
      methodology is implemented to assess the performance of the proposed UFCA with
      respect to the fuzziness index. An interval of choice around 2, a value widely
      used in FCA, is shown to yield the best performance.

PMID- 11231178
TI  - Building 3D sulcal models using local geometry.
AB  - This paper presents a series of 3D statistical models of the cortical sulci. They
      are built from points located automatically over the sulcal fissures, and
      corresponded automatically using variants on the iterative closest point
      algorithm. The models are progressively improved by adding in more and more
      structural and configural information, and the final results are consistent with
      findings from other anatomical studies. The models can be used to locate and
      label anatomical features automatically in 3D MR images of the head, for
      analysis, visualisation, classification, and normalisation.

PMID- 11231181
TI  - Multidrug-resistant strains of Salmonella enterica serotype typhi are genetically
      homogenous and coexist with antibiotic-sensitive strains as distinct, independent
      clones.
AB  - OBJECTIVE: The goal of this study was to report the molecular analysis of
      antibiotic-sensitive and multidrug-resistant (MDR) strains of Salmonella typhi,
      using pulsed-field gel electrophoresis (PFGE), with a particular emphasis on the
      coexistence of these strains in a typhoid-endemic region of Karachi, Pakistan.
      METHODS: One hundred isolates of S. typhi in humans (50 MDR and 50 antibiotic
      sensitive isolates) from sporadic cases of typhoid fever were analyzed by Vi
      phage typing, antibiograms and PFGE. RESULTS: The MDR S. typhi strains were
      resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole.
      Analysis by PFGE showed that 50 MDR isolates of S. typhi had a single, homogenous
      PFGE profile, which was distinctly different from that of 50 antibiotic-sensitive
      isolates obtained in the same time frame from the same area. This latter group of
      isolates showed much greater diversity of PFGE profiles, as has been observed in
      other endemic regions. CONCLUSIONS: Multidrug-resistant and antibiotic
      susceptible strains of S. typhi can coexist in endemic areas as epidemiologically
      independent pathogens and are not in competition for continued persistence and
      transmission.

PMID- 11231180
TI  - Quantification of HIV-1 proviral DNA in patients with undetectable plasma viremia
      over long-term highly active antiretroviral therapy.
AB  - OBJECTIVES: To assess the prognostic role of proviral DNA in peripheral blood
      mononuclear cells (PBMC) of patients with undetectable viremia over long-term
      highly active antiretroviral therapy (HAART). METHODS: Eighty-two human
      immunodeficiency virus (HIV)-1-infected patients, free of acquired
      immunodeficiency syndrome (AIDS), received zidovudine plus lamivudine plus
      indinavir. Levels of plasma HIV-RNA, and PBMC proviral DNA and RNA unspliced (US)
      transcripts were evaluated by using competitive polymerase chain reaction (cPCR)
      assays, every 3 months over 1 year. RESULTS: Among patients with undetectable
      viremia at baseline, 13 of 18 with CD4 cell count 350/mm3 or less and 12 of 16
      with CD4 between 351 and 700/mm3, constantly maintained undetectable RNA levels;
      in these patients, a mean proviral DNA decrease of 0.67 6 0.7 and 1.03 6 0.53 log
      (P < 0.001), respectively, a significant decrease of RNA-US transcripts (P <
      0.001), and significant correlations between decreases of proviral DNA and RNA-US
      transcripts (P = 0.008 and P < 0.001, respectively) were observed. CONCLUSIONS:
      Proviral DNA quantitation permits the continued monitoring of HAART in patients
      with undetectable viremia.

PMID- 11231179
TI  - Changes over time in the epidemiology of diarrhea and malnutrition among children
      in an urban Brazilian shantytown, 1989 to 1996.
AB  - BACKGROUND: Endemic diarrhea and its associated malnutrition remain leading
      causes of childhood morbidity and mortality in developing countries. This study
      was undertaken to describe changes in the incidence of diarrhea and prevalence of
      malnutrition among children in an urban Brazilian shantytown from 1989 to 1996. A
      secondary purpose was to examine associations between malnutrition and increased
      incidence and duration of diarrhea. METHODS: From August 1989 through December
      1996 a dynamic birth cohort of 315 children was followed for surveillance of
      diarrhea and nutrition. Study homes were visited twice or thrice weekly to assess
      the occurrence of diarrhea. Length and weight of the subjects were measured
      quarterly. Poisson regression was used to test for associations between prior
      nutritional status and subsequent diarrhea during a quarter. Multiple regression
      was used to test for an association between nutritional status and episode
      duration. RESULTS: Declines in both age-adjusted attack rates (6.0 episodes/child
      year in study year 3 [1991] to 2.5 episodes per child-year in study year 8 [1996]
      and days of diarrhea per child-year (30.8 days/child-year in year 3 to 8.5
      days/child-year in year 8) were correlated with yearly improvements in mean
      nutritional status (R2= 0.84, P < 0.05, for mean length-for-age with mean number
      of episodes/child-year [corrected]. Both length- and weight-for-age were
      significant predictors of diarrhea incidence, including persistent episodes (> or
      =14 d), but not duration. CONCLUSIONS: These results demonstrate marked changes
      over time in the diarrhea burden and nutritional status of children in this
      population and provide further evidence of a significant association between
      malnutrition and increased incidence of diarrhea.

PMID- 11231182
TI  - Seasonal, nontoxigenic Vibrio cholerae O1 Ogawa infections in the Eastern Region
      of Saudi Arabia.
AB  - BACKGROUND: Surveillance for Vibrio cholerae in the Eastern Region of Saudi
      Arabia has been ongoing since 1985 to detect and prevent local proliferation of
      imported cholera. In 1996 and 1997 the authors performed additional microbiologic
      and epidemiologic assessment of V. cholerae surveillance to better characterize a
      recurrent summertime pattern of V. cholerae infections in the Eastern Region of
      Saudi Arabia. METHODS: All health facilities routinely submitted stool or rectal
      swab specimens for isolation of V. cholerae from patients with gastroenteritis.
      In addition, specimens were taken from expatriate workers and household contacts
      of persons with confirmed V. cholerae infection. Forty-two isolates were
      evaluated for cholera enterotoxin by enzyme-linked immunosorbent assay, cholera
      toxin polymerase chain reaction, and Y1 adrenal cell assay; 12 isolates also were
      characterized by pulsed-field gel electrophoresis (PFGE). Interviews about
      potential exposures were done for all V. cholerae infections. RESULTS: Vibrio
      cholerae O1 serotype Ogawa biotype El Tor was identified in 113 gastroenteritis
      patients (6.0 per 100,000 population per year), 28 asymptomatic expatriate
      workers, and 16 of 982 household contacts of index patients. All symptomatic
      infected persons had mild illness that was not typical of cholera, and all 42
      isolates evaluated were nontoxigenic. All 12 isolates evaluated by PFGE had an
      indistinguishable pattern (pattern 81). Infections appeared in late May,
      decreased in mid-July through August, increased again in September, and
      disappeared from December through April. Infections had a uniform geographic
      distribution and affected all ages. No linkage was identified between affected
      households, or between community cases and food-handlers or domestic servants.
      DISCUSSION: Surveillance in the Eastern Region of Saudi Arabia has identified a
      novel strain of nontoxigenic V. cholerae O1 Ogawa. This strain probably has a
      local environmental reservoir. Since cholera toxin is the primary virulence
      factor involved in the cause of cholera, assays for cholera toxin should be
      included in cholera surveillance.

PMID- 11231183
TI  - Hepatitis B and C viral infections in Indian kala-azar patients receiving
      injectable anti-leishmanial drugs: a community-based study.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) and hepatitis B and hepatitis C
      viruses have emerged as major blood-borne infections. Several cases of infections
      through the use of unsterile injection needles also are on record. Kala-azar, or
      visceral leishmaniasis, is a hemoparasitic disease caused by Leishmania donovani.
      All the anti-kala-azar medications require multiple intramuscular injections of
      the anti-leishmanial drugs. To find whether these patients were at higher risk of
      contracting blood-borne infection, than those who were not on medication, a
      community-based study was conducted in the kala-azar-endemic state of Bihar,
      India. METHODS: Five villages (4050 families) of three highly endemic districts
      of Bihar were included in this study. The sociodemographic data of the affected
      families and their annual income were determined as per Government of India
      guidelines. The diagnosis of kala-azar and its sequelae, post-kala-azar dermal
      leishmaniasis (PKDL), was made, and their therapeutic details were noted. All the
      leishmania-infected patients, their spouses, family members, and villagemates
      were tested for hepatitis B surface antigen, hepatitis C virus antibodies, and
      anti-HIV (1 + 2) antibodies, using commercially available kits. RESULTS: Of the
      4050 families, 61 (1.5%) were found affected with kala-azar or PKDL. These 61
      families had 77 cases of leishmaniasis, of which 64 (83%) had kala-azar and 13
      (17%) PKDL. The most affected (4.5%) age group was 11 to 40 years. Of the 61
      families, 57 (93.4%) families belonged to so-called untouchable castes, and 9 of
      them could not afford to have any anti-kala-azar treatment. Only 64 patients
      received treatment in the form of injectables. The number of injections received
      by these patients ranged from 3 to 120. Hepatitis B and C viral infections were
      found to be significantly more prevalent in those who received multiple
      injections. Compared to their male counterparts infected with L. donovani,
      females who received injectable medicines were at higher risk of contracting
      hepatitis B infections (20% vs. 11.3%) and hepatitis C virus infection (26.7% vs.
      18.9%). Overall, hepatitis C virus infections were more common (20.6%) than
      hepatitis B virus infection (13.2%) in this group of patients. Villagemates with
      a history of injections for other ailments also were found to have a high rate of
      infection with hepatitis viruses. One patient with kala-azar was found to be co
      infected with HIV, although probably not related to injections. CONCLUSIONS: The
      treatment of Indian kala-azar and post-kala-azar dermal leishmaniasis consists of
      multiple intramuscular injections of sodium stibogluconate, pentamidine, or
      amphotericin B. Though the original disease gets cured, all these therapeutic
      regimens were found to carry a significantly high risk of transmitting yet more
      dangerous blood-borne infections, such as HIV and hepatitis B and C viruses,
      through the shared use of unsterile injection needles. All needles should be
      appropriately sterilized, if they are to be re-used.

PMID- 11231184
TI  - Epidemiology of human immunodeficiency virus and acquired immunodeficiency
      syndrome in Lebanon from 1984 through 1998.
AB  - OBJECTIVE: To identify the epidemiologic characteristics of human
      immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) in
      Lebanon during the period between January 1, 1984, and December 31, 1998.
      MATERIALS AND METHODS: This report presents a descriptive analysis of HIV and
      AIDS surveillance data. The subjects of this study were all notified HIV and AIDS
      cases in Lebanon reported to the Epidemiological Surveillance Unit of the
      Department of Preventive Medicine at the Ministry of Public Health in Lebanon.
      RESULTS: The HIV epidemic started in Lebanon in 1984 with the first diagnosed
      AIDS cases. The number of cases slowly but steadily increased, to reach, by 1998,
      529 cases, of which 147 were AIDS cases. The average age of infected persons was
      31 years, with a ratio of men to women close to 3.6:1. The most frequent mode of
      transmission is sexual (71.9% of all cases; heterosexual, 53.9% of all cases),
      which consequently increases the perinatal transmission of the disease (4.3% of
      all declared cases). Data on high-risk groups (intravenous drug users,
      homosexuals, prostitutes, and prisoners) are incomplete, although the problem
      does exist. The safety of blood products is relatively well controlled in the
      country. No new cases of HIV infections through blood transfused in Lebanon have
      been reported since 1993 (8.5% of all cases). CONCLUSION: The continuously
      increasing number of HIV and AIDS cases shows an urgent need for targeted
      interventions in the general population to stop any further spread of HIV
      infections in the years to come.

PMID- 11231185
TI  - Trends in antimicrobial resistance and serotype distribution of blood and
      cerebrospinal fluid isolates of Streptococcus pneumoniae in South Africa, 1991
      1998.
AB  - OBJECTIVE: Since 1979, the South African Institute for Medical Research (SAIMR)
      has served as the national reference center for pneumococcal serotyping and
      monitoring of antibiotic resistance trends. This study documents trends in
      antimicrobial resistance in pneumococci isolated from blood or cerebrospinal
      fluid (CSF) between 1991 and 1998 in South Africa. METHODS: Pneumococcal isolates
      (n = 7406) from either blood or CSF were sent to the SAIMR reference laboratory
      for serotyping. The isolates were evaluated for resistance to penicillin,
      chloramphenicol, tetracycline, erythromycin, clindamycin, and rifampicin.
      RESULTS: Resistance to one or more antibiotics increased significantly from 19%
      in 1991 to 1994 to 25% in 1995 to 1998 in all ages, and in children from 32% to
      38% (P < 10[-6]). Although penicillin resistance did not increase in children
      (28.1% vs. 28.9%), penicillin resistance in all ages increased from 9.6% to
      18.0%. Significant increases in resistance to chloramphenicol, tetracycline,
      erythromycin, and rifampicin also were seen in both groups. Multiple resistance
      increased significantly, from 2.2% to 3.8%. The proportion of isolates with
      intermediate or high-level penicillin resistance remained constant during the
      surveillance period. Erythromycin resistance, predominantly expressed as
      simultaneous resistance to erythromycin and clindamycin, increased from 1.6% to
      2.6%. The percentage of erythromycin-resistant isolates that were resistance to
      erythromycin alone increased from 10.6% to 28.7%, suggesting the emergence of
      mefE-mediated resistance. In children 2 years of age and younger, although
      serogroup 6 remained the most common, there were significant increases in
      serogroups 19, 18, and 13. The percentage of the total invasive pneumococcal
      disease in this population that is caused by serogroups found in the nonavalent
      pneumococcal conjugate vaccine (serogroups 1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F)
      increased from 72% to 91%. CONCLUSIONS: Antibiotic resistance in the pneumococcus
      is increasing in South Africa, although the proportion of strains with high-level
      penicillin resistance has not increased. New conjugate vaccines may not only
      decrease the burden of all pneumococcal disease but, in addition, lower the
      incidence of antibiotic-resistant disease in South Africa.

PMID- 11231186
TI  - Appendicitis and chronic typhilitis in an immigrant from Southeast Asia.

PMID- 11231187
TI  - Global infectious disease surveillance.

PMID- 11231188
TI  - Primary tuberculosis of the parotid gland.

PMID- 11231189
TI  - Rationale for a hospital-based pneumococcal vaccine trial for HIV-seropositive
      South Africans.

PMID- 11231190
TI  - Food irradiation and vitamin loss.

PMID- 11231191
TI  - Are there valid concerns about food irradiation?

PMID- 11231193
TI  - Multiple indurated papules on penis and scrotum.
AB  - BACKGROUND: Sarcoidosis is a chronic disease with involvement of multiple organs.
      Cutaneous lesions may appear as the only manifestation or may be accompanied by
      systemic disease. OBJECTIVE: To learn that genital sarcoidosis is a rare entity
      that should be included in the differential diagnosis of genital papules and
      nodules. METHODS AND RESULTS: A 31-year-old African-American man presented with
      cutaneous lesions on his penis and scrotum existing for 2 years. The genital
      lesions were so prominent as to interfere with his sexual life. Sarcoidosis was
      demonstrated on biopsy. CONCLUSIONS: Sarcoid lesions may affect any skin area,
      but are rarely described on the genitalia. Dermatologists should be aware that
      genital sarcoidosis is a rare entity that should be included in the differential
      diagnosis of genital papules and nodules. Additionally, genital sarcoidosis may
      cause urinary problems and may represent a therapeutic challenge.

PMID- 11231194
TI  - Are sterile conditions essential for all forms of cutaneous surgery? The case of
      ritual neonatal circumcision.
AB  - BACKGROUND: Many aspects of cutaneous surgical interventions have been perfected,
      employed, and then scientifically examined. Conversely, ubiquitous,
      indiscriminate demand for sterile conditions while performing an invasive
      procedure remains a field devoid of satisfactory critical appraisal. OBJECTIVE:
      Ritual neonatal circumcision served as a prototype to assess scientifically the
      safety of performing a dermatologic intervention under clean, uncontaminated, but
      nonsterile conditions. METHODS: Two hundred subjects, mostly neonates, who were
      unselectively referred for ritual circumcision, served as the study group. The
      guillotine excisional technique was employed in the community setting under
      clean, uncontaminated, nonsterile conditions, in line with traditional practice.
      Follow-up was continued until full recovery. RESULTS: No wound infections or
      septic complications were observed in any of the babies at either early (24-36
      hours after the procedure) or late follow-up. Many subjects had an exudative
      discharge at the healing site several days after the procedure. This is a common
      finding associated with circumcision and was found to be nonindicative of
      infection. CONCLUSIONS: This preliminary study suggests that strict sterile
      conditions are superfluous for ritual neonatal circumcision, and the effort and
      expense invested in maintaining an aseptic environment for this sort of
      intervention may not be justified. Further large-scale investigations are
      warranted to validate these findings and to determine if they can be extrapolated
      to other patient populations and other types of cutaneous surgery.

PMID- 11231195
TI  - Scanning electron microscopy of adult head lice (Pediculus humanus capitis) with
      focus on clinical implications.
AB  - BACKGROUND: The incidence of head lice infestations in North America is
      escalating with an estimated 12 million cases of head lice per year despite the
      existence of insecticidal therapies. OBJECTIVE: To evaluate certain
      characteristics of the human head louse, including their chitinous structure,
      nymphal developmental stages, legs with claw adaptations, antennae with sensory
      perceptions, and spiracles by which oxygen exchange occurs, for assessment of
      possible means to control the spread and growth of this insect. METHODS: Scanning
      electron-microscopic examination of head lice was performed. RESULTS: Newer
      treatments of head lice must acknowledge defense mechanisms that are based on
      anatomic structure and physiologic characteristics, details of louse
      transmission, and the insects' ability to 'resurrect' after sham death.
      CONCLUSIONS: An understanding of lice entomology is essential in the pursuit of
      novel means to control the lice epidemic.

PMID- 11231196
TI  - Merkel cell carcinoma of the skin.
AB  - BACKGROUND: Neuroendocrine/Merkel cell carcinoma (MCC) of the skin is an uncommon
      tumour. Currently, there are only limited data available on the natural history,
      prognostic factors, and patient management of MCC. OBJECTIVES: To review our
      experience and build the largest database from the literature. METHODS: Twenty
      eight cases from the London Regional Cancer Center were combined with 633 cases
      obtained from the literature searched in English, French, German, and Chinese for
      the years 1966 to 1998. The database included age, sex, initial disease status at
      presentation to the clinic, site of primary, any coexisting disease, any previous
      irradiation, sizes of primary/nodal/distant metastases, management details, and
      final disease status. A new modified staging system was used: stage Ia (primary
      disease only, size > 2 cm), stage Ib (primary disease only, size > 2 cm); stage
      II (regional nodal disease), and stage III (beyond regional nodes and/or distant
      disease). RESULTS: Age > 65 years, male sex, size of primary > 2 cm, truncal
      site, nodal/distant disease at presentation, and duration of disease before
      presentation (< or =3 months) were poor prognostic factors. Surgery was the
      initial treatment of choice and it significantly improved overall survival (p
      =.004). CONCLUSIONS: We identified poor prognostic factors that may necessitate
      more aggressive treatment. The suggested staging system, incorporating primary
      tumour size, accurately predicted outcomes.

PMID- 11231197
TI  - Transmittance properties of flurandrenolide tape for psoriasis: helpful adjunct
      to phototherapy.
AB  - BACKGROUND: Flurandrenolide tape is a valuable agent in the treatment of lichen
      simplex chronicus and in psoriasis. The corticosteroid is helpful for reducing
      the symptoms and induration of the lichen simplex chronicus lesion, and occlusion
      of the lesion with the tape reduces the patient's opportunity to rub and scratch
      the affected area. OBJECTIVES: The purpose of this study was to determine to what
      extent flurandrenolide tape may block ultraviolet (UV) light and interfere with
      phototherapy of psoriasis. METHODS: Flurandrenolide tape was applied to quartz
      spectroscopy cuvettes, and the absorption spectrum was determined using a Beckman
      DU-600 spectrophotometer. The effect of the tape on UV light transmission was
      also determined using our UVA-UVB office phototherapy unit. RESULTS:
      Flurandrenolide tape has considerable UV absorption in the UVC range with less
      absorption in the UVB and UVA range. The transmittance is greater (less
      absorption) with longer wavelengths. There was greater UV absorption in the UVB
      range than in the UVA range. CONCLUSION: Although flurandrenolide tape may be
      left in place during PUVA therapy, adjustment of UV dose or removal of the tape
      is probably needed during UVB phototherapy.

PMID- 11231198
TI  - Clinical evidence of lice resistance to over-the-counter products.
AB  - BACKGROUND: Over-the-counter insecticidal solutions continue to be the mainstream
      treatment for most cases of head lice. Recorded insecticidal activity 15 years
      ago was at 100%, with ovicidal kill at 80%. Recently scattered accounts of
      possible resistance have surfaced. OBJECTIVE: This article is to document the
      general consensus that head lice are becoming resistant to standard over-the
      counter therapies. METHODS: Direct testing of lethality of adult lice with
      permethrin and pyrethroid was assessed. RESULTS: Present over-the-counter
      products proved to be successful in only 9 of 32 head lice tested (28%
      insecticidal activity). CONCLUSIONS: Our series of cases further documents that
      over-the-counter head lice preparations no longer achieve high levels of
      insecticidal activity, suggesting increased resistance to these insecticides.

PMID- 11231199
TI  - Cicatricial pemphigoid diagnosed by the use of indirect immunofluorescence.
AB  - BACKGROUND: A thorough work-up is paramount in the accurate diagnosis of oral
      erosive diseases. OBJECTIVE: A case of pemphigoid with negative direct
      immunofluorescence but positive indirect immunofluorescence is presented. METHODS
      AND RESULTS: A 77-year-old man presented with erosions of the oral and glans
      mucosa and with esophageal stenosis. Histologic examination revealed nonspecific
      mucositis. Indirect immunofluorescence was characteristic of pemphigoid.
      CONCLUSION: This case illustrates the importance of performing a complete
      diagnostic work-up in the evaluation of patients with oral erosive disease.

PMID- 11231200
TI  - Male Paget's disease of the breast.
AB  - BACKGROUND: Paget's disease is an extremely rare condition of the male breast
      that presents as an eczematous change of the nipple and areola. It is almost
      always associated with an underlying intraductal carcinoma. OBJECTIVE: A case of
      Paget's disease of the male breast with extension into adnexal structures is
      reported. MATERIALS AND METHODS: A MEDLINE search for cases of Paget's disease of
      the male breast was performed and the cases were reviewed. The following
      antibodies were used in immunohistochemical staining: Rabbit Anti-Human c-erbB-2
      Oncoprotein, monoclonal Mouse Anti-Human Estrogen Receptor (IgG1, kappa), and
      monoclonal Mouse Anti-Human Progesterone Receptor (Clone PgR 636). RESULTS: This
      is only the 43rd histologically proven case of Paget's disease of the male breast
      in the world literature and, to our knowledge, the first to document extension of
      Paget's cells into adnexal structures, including eccrine glands. CONCLUSION:
      Mammary Paget's disease is a rare phenomenon among men.

PMID- 11231201
TI  - Calciphylaxis: seven new cases.
AB  - BACKGROUND: Calciphylaxis is a rare condition occurring most frequently in
      patients with end-stage renal disease (ESRD). It is characterized by vascular
      calcifications with a large variety of skin lesions. Even though this entity was
      first reported almost 50 years ago, the pathogenesis is still not well
      understood. OBJECTIVE: Having retrieved seven new cases from a single tertiary
      care hospital, the disease occurs probably more frequently than reported until
      now. The potential mechanism of action in this disease is discussed, particularly
      the hypercoagulability state. We also review potential treatments described in
      the literature. METHODS: Seven patients with calciphylaxis that occurred at the
      Hotel-Dieu hospital between 1992 and 1998 were identified and their case
      histories reviewed and analyzed. CONCLUSION: Although hyperparathyroidism and
      imbalance of calcium-phosphorus homeostasis are paramount for calciphylaxis to
      occur, other mechanisms must be involved because the disease manifests itself in
      only a minority of ESRD patients. As the majority were under anticoagulation
      therapy and as we found abnormalities of the coagulation pathway in one patient,
      we suggest emphasizing these phenomena in the future. Along with evaluation of
      putative risk factors (abnormalities of the calcium:phosphate axis, diabetes), a
      detailed evaluation of the coagulation system should be done in every patient
      with calciphylaxis until more data are available.

PMID- 11231203
TI  - Travel clinics and public health.

PMID- 11231202
TI  - Serum sickness.
AB  - BACKGROUND: In the late 19th and early 20th century there was much interest in
      understanding the reactions to diphtheria antitoxin and the horse serum in which
      it was produced and administered. OBJECTIVE: Pirquet and Schick reported on their
      studies of these reactions; particularly the differences in the reaction of those
      patients who had only one injection, and those who had a re-injection.
      CONCLUSION: Pirquet and Schick concluded that "due to a single injection of horse
      serum a change takes place in the reaction of the human organism to the re
      introduction of the same substance." This change, Pirquet in a 1906 article,
      called allergy.

PMID- 11231204
TI  - Neuropsychiatric events and travel: do antimalarials play a role?

PMID- 11231205
TI  - Death and dying abroad: the Canadian experience.
AB  - BACKGROUND: The objective was to examine the characteristics of international
      travelers from Canada, who have died while abroad, and to review the health
      protection and promotion strategies for prevention of adverse health outcomes
      associated with travel, which may have prevented these deaths. METHOD: An EpiInfo
      6 program was created to analyse all of the Consular reports received in 1995 via
      the Secure Integrated Global Network, which provides communications and
      computerization services to the Department of Foreign Affairs and International
      Trade, Canada. The Consular Management and Operations System was designed to
      support the delivery of consular services by the Department, and to link
      Headquarters in Ottawa with missions in other countries, through case management
      files, including a "Death Abroad" file. The type of data collected included
      personal demographics (age, gender), date, country, and cause of death. RESULTS:
      In 1995, consular services received 309 reports of Canadians dying abroad. Two
      hundred and twenty deaths were males (71.2%), and 69 were females (22.3%). The
      average age (56 years) and median age (43 years) were similar for males and
      females (age range 0.3-86 years). Recorded causes of death were: natural (62.1%),
      accidents (24.9%), murder (7.8%), and suicide (5.2%). Cardiovascular disease and
      trauma were the two most commonly specified causes of death. CONCLUSIONS: At
      least 36% of the deaths occurring in Canadian travelers would be considered
      preventable. Pretravel medical interventions for travelers with known preexisting
      medical problems, may have prevented many more deaths. International travelers
      need to be aware of the health risks associated with travel. Access to
      appropriate health risk assessment, prior to exposure, in many cases, would have
      prevented death abroad.

PMID- 11231206
TI  - Health and safety problems and lack of information among international visitors
      backpacking through North Queensland.
AB  - BACKGROUND: International visitors to tropical Australia may be exposed to health
      and safety problems. Because they are younger, stay longer and participate in
      more activities, backpackers have a greater exposure to such problems than other
      visitors. METHOD: The study's aim was to determine how many backpackers
      experience problems and lack health and safety information. Four hundred and
      thirty-one international visitors staying in a random sample of youth hostels and
      backpacker accommodation in Townsville were surveyed over the summer. RESULTS:
      Sixty two percent experienced a health and safety problem, commonly, insect
      bites, sunburn, headaches, lacerations, coral cuts, ear infections and diarrhea.
      Seventeen percent resolved only with professional help. Only 54% of backpackers
      had been offered health and safety information prior to departure, mainly
      vaccination advice. CONCLUSION: The proportion of backpackers offered health and
      safety information about tropical Australia, and the breadth of that information,
      needs to be increased.

PMID- 11231207
TI  - Safety in New Zealand's adventure tourism industry: the client accident
      experience of adventure tourism operators.
AB  - BACKGROUND: Injuries and fatalities among participants of adventure tourism
      activities have the potential to seriously impact on New Zealand's tourism
      industry. However, the absence of statistics for tourist accidents in New
      Zealand, and the lack of detailed academic research into adventure tourism
      safety, means the extent of the problem is unknown. The aims of the present study
      were to determine the incidence of client injuries across a range of adventure
      tourism activity sectors, and to identify common accident events and contributory
      risk factors. METHOD: A postal questionnaire survey of New Zealand adventure
      tourism operators was used. Operators were asked to provide information related
      to their business; the number of recorded client injuries during the preceding 12
      month period, January to December 1998; common accident and injury events
      associated with their activity; and perceived risk factors for accidents in their
      sector of the adventure tourism industry. RESULTS: The survey was responded to by
      142 New Zealand adventure tourism operators. The operators' reported client
      injury experience suggests the incidence of serious client injuries is very low.
      Highest client injury incidence rates were found for activities that involved the
      risk of falling from a moving vehicle or animal (e.g., cycle tours, quad biking,
      horse riding, and white-water rafting). Slips, trips, and falls on the level were
      common accident events across most sectors of the industry. Perceived
      accident/incident causes were most commonly related to the client, and in
      particular, failure to attend to and follow instructions. CONCLUSIONS: The
      prevalence of client injuries in activity sectors not presently covered by
      government regulation, suggests policy makers should look again at extending
      codes of practice to a wider range of adventure tourism activities. Further
      research considering adventure tourism involvement in overseas visitor
      hospitalized injuries in New Zealand, is currently in progress. This will provide
      supporting evidence for the risk associated with participation in a range of
      commercial and independently undertaken adventure activities.

PMID- 11231208
TI  - A single dose, combined vaccine against typhoid fever and hepatitis A:
      consistency, immunogenicity and reactogenicity.
AB  - BACKGROUND: Vaccines against hepatitis A and typhoid fever are well established
      and have an excellent safety and immunogenicity profile. Yet these diseases,
      which share the same geographic distribution, remain an important cause of
      morbidity in travelers to endemic countries. Combined vaccination provides dual
      protection and improves compliance and coverage for travelers. METHODS: This
      multicenter study evaluated the consistency of three lots of combined hepatitis A
      and typhoid fever vaccine. A total of 462 healthy subjects, aged 15-50 years,
      were enrolled and randomly allocated to 3 groups. The single dose of vaccine
      contains 25 microg typhoid Vi polysaccharide and at least 1,440 ELISA units of
      inactivated hepatitis A in a 1 mL dose. RESULTS: Bioequivalence of all production
      lots was shown in terms of safety and immunogenicity. Pain at injection site was
      the most frequent reported local symptom, and headache was the most frequent
      reported general symptom. As early as 14 days after immunization >95% of the
      subjects were positive for anti-Vi antibodies and >86% were positive for anti-HAV
      antibodies. The GMTs and seropositivity rates were maintained during the 6 month
      follow-up. CONCLUSION: The first combined vaccine against typhoid fever and
      hepatitis A was safe and elicited a very good immune response, with the majority
      of subjects seropositive at 1 month for both antigens. This combined vaccine
      offered more convenience and rapid seroconversion to travelers.

PMID- 11231209
TI  - Use of medical chemoprophylaxis and antimosquito precautions in Danish malaria
      patients and their traveling companions.
AB  - BACKGROUND: The number of malaria cases imported to Denmark has been increasing
      for some years. To analyze the background for this we assessed the use of
      protective measures in Danish travelers visiting malarious areas. METHOD: Post
      travel questionnaires were given during hospitalization to malaria patients, and
      sent by mail to their traveling companions. RESULTS: In total, 142 persons
      participated. Only 32% of the travelers used chemoprophylaxis correctly,
      according to Danish recommendations. Twelve percent of the travelers did not use
      chemoprophylaxis. Average compliance was 52%. Insufficient drug dosage was
      reported by 13%, and use of nonrecommended drugs by 7% of the travelers. Thirty
      seven percent used insufficient antimosquito precautions, a problem which often
      coincided with irregular use of chemoprophylaxis. Malaria patients, sole
      travelers, and travelers with other ethnical background than Danish, were
      subgroups using insufficient malaria prophylaxis more frequently than healthy
      traveling companions. CONCLUSION: Insufficient use of the available antimalaria
      precautions by Danish travelers contributes greatly to maintaining a high
      incidence of imported malaria. Increased attention from physicians in educating
      travelers is important for optimizing malaria prophylaxis.

PMID- 11231210
TI  - Health problems in a large cohort of Americans traveling to developing countries.
AB  - BACKGROUND: Millions of Americans visit developing countries each year, however,
      little is known about their health during travel. This study describes health
      problems in a large cohort of American travelers during and after their trip.
      METHODS: A 2-year survey of 784 travelers (95% follow-up) was conducted for
      persons traveling for < or = 90 days. At the pretravel visit, travelers were
      given a postcard to record adverse health events. Following travel, standardized
      telephone interviews were performed for any positive responses, or if the card
      was not returned. All travelers were contacted 2 months after return to determine
      late occurring illness and compliance with antimalarials. RESULTS: Travelers had
      a mean age of 44 years, a median duration of 19 days, and visited 123 countries.
      An illness was reported by 64% (1.6 illnesses per traveler). Ill travelers were
      more often female, and traveled longer than those who were not ill; depending
      upon destination, each day of travel increased by 3 to 4% the chance of becoming
      ill. Diarrhea was most common, occurring in 46%; 34% met a strict definition for
      traveler's diarrhea. Respiratory illness occurred in 26%, skin disorders in 8%,
      acute mountain sickness in 6%, motion sickness in 5%, accidents and injuries in
      5%, and isolated febrile episodes in 3%. Medical care was sought by 8% of all
      travelers and 12% of those reporting illness. On return, 26% of travelers were
      ill, 56% of whom became ill after return. Diarrhea, respiratory illness, skin
      disorders, and febrile syndromes were most common, and 46% of those who were ill
      sought medical care. Complete compliance with antimalarials was 80%. Noncompliant
      individuals usually discontinued medications on return. Side effects were
      reported by 4% of those taking chloroquine, 11% of those taking chloroquine plus
      proguanil, and 14% of those taking mefloquine, with half of these
      neuropsychiatric. The incidence of documented malaria was 3.8 cases per 1,000
      travelers. CONCLUSIONS: Many travelers experience adverse health events during
      and after travel to the developing world. Attention to the prevention and therapy
      of traveler's diarrhea, prophylaxis of malaria, management of respiratory
      illness, personal safety, and access to medical care during travel, and,
      recognition of clinical syndromes after return, will help to improve the
      traveler's health.

PMID- 11231211
TI  - Travel medicine advice to UK based international motor sport teams.
AB  - BACKGROUND: International motor sport teams travel extensively. Over the years,
      the design and build of racing cars has improved so that morbidity and mortality
      in motor sport has been lessened. Those team members supporting the competitors
      need to be physically and mentally fit to perform complicated tasks, despite
      having traveled. This group of travelers has not been studied to any extent
      previously. METHOD: An anonymous questionnaire asking some basic travel medicine
      related questions was distributed to the support team members of a Rally team,
      and Formula One Grand Prix team. Both teams were based in the UK, and competed in
      all the rounds of their respective world championships. RESULTS: Ten Rally team
      members and 18 Formula One team members responded to the questionnaire. The
      results showed moderate coverage of commonly used vaccinations; appropriate use
      of antimalarials and insect repellents, but by no means by all team members;
      little or no problems with traveler's diarrhea; some tendencies to problems
      related to jet lag, but no real attempt to prevent the problem; and finally some
      attempt at skin protection against solar damage. CONCLUSION: Support teams are
      reasonably well prepared for the combination of, the rigors of frequent travel,
      and a demanding job. There is a deficit in vaccine coverage, especially of both
      hepatitis A and B, some education is needed in preventing skin problems later in
      life due to sun exposure, and further study of jet lag and its implications might
      be appropriate.

PMID- 11231212
TI  - Malaria in Brazilian military personnel deployed to Angola.
AB  - BACKGROUND: Malaria represents one of the most important infectious disease
      threats to deployed military forces; most personnel from developed countries are
      nonimmune personnel and are at high risk of infection and clinical malaria. This
      is especially true for forces deployed to highly-endemic areas in Africa and
      Southeast Asia where drug-resistant malaria is common. METHODS: We conducted an
      outbreak investigation of malaria cases in Angola where a total of 439 nonimmune
      Brazilian troops were deployed for a 6-month period in 1995-1996. A post-travel
      medical evaluation was also performed on 338 (77%) of the 439 soldiers upon
      return to Brazil. Questionnaire, medical record, thick/thin smear, and serum anti
      Plasmodium falciparum antibody titer (by IFA) data were obtained. Peak serum
      mefloquine (M) and methylmefloquine (MM) metabolite levels were measured in a
      subsample of 66 soldiers (42 cases, 24 nonmalaria controls) who were taking
      weekly mefloquine prophylaxis (250 mg). RESULTS: Seventy-eight cases of malaria
      occurred among the 439 personnel initially interviewed in Angola (attack rate =
      18%). Four soldiers were hospitalized, and 3 subsequently died of cerebral
      malaria. Upon return to Brazil, 63 (19%) of 338 soldiers evaluated were
      documented to have had clinical symptoms and a diagnosis of malaria while in
      Angola. In addition, 37 (11%) asymptomatically infected individuals were detected
      upon return (< 1% parasitemia). Elevated, post-travel anti-P. falciparum IFA
      titers (> or = 1:64) were seen in 101 (35%) of 292 soldiers tested, and was
      associated with a prior history of malaria in-country (OR = 3.67, 95% CI 1.98
      6.82, p <.001). Noncompliance with weekly mefloquine prophylaxis (250 mg) was
      associated with a malaria diagnosis in Angola (OR = 3.75, 95% CI 0.97-17.41, p
      =.03) but not with recent P. falciparum infection (by IFA titer). Mean peak
      levels (and ratios) of serum M and MM were also found to be lower in those who
      gave a history of malaria while in Angola. CONCLUSIONS: Malaria was a significant
      cause of morbidity among Brazilian Army military personnel deployed to Angola.
      Mefloquine prophylaxis appeared to protect soldiers from clinical, but not
      subclinical, P. falciparum infections. Mefloquine noncompliance and an erratic
      chemoprophylaxis prevention policy contributed to this large outbreak in
      nonimmune personnel. This report highlights the pressing need for development of
      newer, more efficacious and practical, prophylactic drug regimens that will
      reduce the malaria threat to military forces and travelers.

PMID- 11231213
TI  - Scuba diving and snorkeling safety on Australia's Great Barrier Reef.

PMID- 11231216
TI  - Typical semiology of benign childhood epilepsy with centrotemporal spikes
      (BCECTS).
AB  - The ILAE (1989) has defined benign childhood epilepsy with centro-temporal spikes
      (BCECTS) as follows: BCECTS is a syndrome of brief, simple, partial, hemifacial
      motor seizures, frequently having associated somatosensory symptoms which have a
      tendency to evolve into generalised tonic clonic seizures (GTCS) [1]. Both
      seizure types are often related to sleep. Onset occurs between the ages of 3 and
      13 years (peak 9-10 years) and recovery occurs before the age of 15-16 years.
      Genetic predisposition is frequent, and there is a male predominance. The EEG has
      blunt high-voltage centrotemporal spikes, often followed by slow waves that are
      activated by sleep and tend to shift or spread from side to side.

PMID- 11231217
TI  - Atypical semiology of rolandic epilepsy in some related syndromes.
AB  - Atypical seizures, especially generalized or focal atonic attacks and atypical
      absences may occur in association with the classical seizures of rolandic
      epilepsy. They are often associated with unusual EEG features, especially a
      marked activation of paroxysms during sleep that may amount to continuous spike
      wave complexes of slow sleep. These electroclinical features are often
      accompanied by cognitive and/or behavioral disturbances and may belong to several
      syndromes (atypical benign partial epilepsy, syndrome of continuous spike-waves
      during sleep, Landau-Kleffner syndrome and status of rolandic epilepsy) whose
      relationship with typical rolandic epilepsy and among themselves remains to be
      clarified.

PMID- 11231218
TI  - Atypical benign partial epilepsy/pseudo-Lennox syndrome.
AB  - The purpose of this report is to describe the full clinical and
      electroencephalograpic spectrum of atypical benign partial epilepsy (ABPE) or
      pseudo-Lennox syndrome (PLS). We retrospectively analyzed the clinical and EEG
      data of 43 children with ABPE/PLS seen in our department during the last 25
      years. Criteria for diagnosis of ABPE/PLS were the occurrence of generalized
      minor seizures as previously described for ABPE/PLS and the detection of focal
      sharp waves indistinguishable from those of rolandic epilepsy (RE) with
      generalization during slow sleep. Mental development prior to onset of epilepsy
      was retarded in 26% of patients. In 74%, age at onset of seizures ranged from 2-5
      years of age. Atonic-astatic seizures, atypical absences, and more rarely,
      myoclonic seizures were the predominating seizure types in 67% of patients.
      Status of minor seizures occurred in 40%. One or several episodes of partial and
      secondarily generalized seizures were observed. Rolandic seizures occurred in
      28%. The EEG was characterized by a normal or slightly slowed background activity
      and predominantly multi-focal sharp waves (88%) which were activated to a
      bioelectrical status in 56% during sleep. No tonic seizures and no fast > 10 Hz
      spike discharges were observed in any of the 1.291 EEG of the patients. Despite
      an often temporarily therapy-resistant course which led to use of steroids in 51%
      of patients, seizures had ceased in 84% and epileptic discharges had disappeared
      in 72% of patients at last follow-up. All patients older than age 15 were seizure
      free. However, the rate of mentally handicapped patients had more than doubled
      from 26 to 56%. EEG which could be performed in 41 out of 56 siblings
      demonstrated shw in 40% of siblings in whom EEG were done at the age of maximum
      penetrance of sharp waves (3-10 years). ABPE/PLS overlaps broadly with RE, but
      also with electrical status epilepticus during sleep and Landau-Kleffner
      syndrome. Therefore, ABPE/PLS can be ranked alongside RE and other idiopathic
      partial epilepsies. The high incidence of sharp waves in siblings suggests that
      ABPE/PLS and RE have a common underlying genetic etiology.

PMID- 11231219
TI  - Autosomal dominant rolandic epilepsy with speech dyspraxia.
AB  - Autosomal Dominant Rolandic Epilepsy with Speech Dyspraxia (ADRESD) is a rare
      disorder which highlights the relationship between Benign Rolandic Epilepsy (BRE)
      and speech and language disorders. Subtle speech and language disorders have
      recently been well characterised in BRE. ADRESD is associated with long term,
      more severe speech and language difficulties. The time course of rolandic
      epilepsy in ADRESD is typical of that of BRE. ADRESD is inherited in an autosomal
      dominant manner with anticipation. It is postulated that the anticipation may be
      due to an, as yet unidentified, triplet repeat expansion in a gene for rolandic
      epilepsy. BRE follows complex inheritance but it is possible that ADRESD may hold
      some valuable clues to the pathogenesis of BRE.

PMID- 11231220
TI  - Rolandic discharges in benign childhood epilepsy with centrotemporal spikes, and
      in other forms of partial epilepsies.
AB  - Previous reports concerning benign childhood epilepsy with centrotemporal spikes
      (BECT) were re-investigated, including new data concerning both the presentation
      of the long-term clinical courses of three cases and the results of
      magnetoencephalography (MEG) in one patient, with respect to the following
      points; (1) the electro-clinical characteristics of sylvian seizures and rolandic
      discharges (RD), and (2) long-term outcome of idiopathic and symptomatic partial
      epilepsies with RD other than BECT. The epileptic focus of sylvian seizures is
      located either in the inferior rolandic cortex or underneath the sylvian fissure,
      which is strongly supported by the results of clinical seizure manifestations,
      ictal and interictal EEG findings, and interictal MEG findings. The presence of
      rolandic discharges is not a hallmark of benign outcome. Instead, the presence of
      sylvian seizures heralds a benign outcome of partial epilepsy regardless of the
      presence or absence of an organic lesion. The pathophysiological mechanism of
      BECT remains unknown. Further neurophysiological as well as genetic
      investigations are needed.

PMID- 11231221
TI  - Epileptiform discharges in benign focal epilepsy of childhood.
AB  - The electroclinical syndrome of benign focal epilepsy of childhood has been the
      subject of intense investigation over the past fifty years. Characteristic
      findings, over the years, of its signature electroencephalographic discharge,
      including morphology, topography, field of distribution, activation and
      reactivity will be presented and discussed.

PMID- 11231222
TI  - Migraine and the benign partial epilepsies of childhood: evidence for an
      association.
AB  - There is an increasing body of evidence to suggest that benign rolandic epilepsy
      and benign occipital epilepsy of childhood are frequently associated with
      migraine. This however has not been universally recognized. Clearly further
      investigation of this association is required. The purpose of this report is to
      examine the varied diagnostic criteria for common migraine utilized by
      epileptologists and other neurologists, to review clinical migraine epilepsy
      relationships, EEG abnormalities in migraine and epilepsy, and the association of
      seizures with vascular headache in patients with various forms of epilepsy.
      Hopefully, this will stimulate further research into this intriguing association
      of two conditions which though they have different pathophysiology frequently
      coexist.

PMID- 11231223
TI  - Benign epilepsies of childhood--distinct syndromes and overlap.
AB  - No clear limits exist between benign partial and generalised epilepsies of
      childhood, and age related transient epilepsies that produce cognitive troubles,
      such as epileptic encephalopathy with continuous spike waves in slow sleep and
      myoclonic astatic epilepsy. Genetic predisposition seems to determine whether the
      epilepsy is partial or generalised. However, some maturational process seems to
      contribute in the cases with transient worsening including cognitive troubles.

PMID- 11231224
TI  - The concept of hereditary impairment of brain maturation.
AB  - The classification of benign partial epilepsies and related conditions includes
      (besides rolandic epilepsy) atypical benign partial epilepsy, bioelectrical
      status epilepticus (ESES) and a variety of other syndromes. The broad overlap of
      the clinical and bioelectrical symptomatology might reflect a pathogenetic
      background common to these epilepsies. In order to understand the great
      phenotypic variability, the clinical symptomatology in 56 sibships with focal
      sharp waves of genetic origin was analyzed. A genetic determination was assumed
      if, in addition to the index case, at least one sibling or offspring revealed
      typical focal sharp waves. The 56 index-cases and their 61 sib/offspring/parents
      showed a broad spectrum of epileptic and non-epileptic conditions ranging from
      mild selective performance deficits to severe complex mental retardation, from
      neonatal seizures, febrile convulsions, and simple rolandic epilepsy to severe
      epilepsies with minor seizures or ESES. The different conditions are not disease
      entities but sets of variably weighted symptoms of a complex pathogenetic
      background, in which a genetic disposition to focal anomalies of brain function
      is of decisive importance. As can be demonstrated by the data, this genetic
      liability coincides with other widespread genetic traits, expressed in certain
      EEG patterns, as well as with lesional pathogenetic factors. The biological
      background of the genetic focal anomaly is currently unknown. The marked age
      dependence of the symptoms justifies the assumption of an hereditary impairment
      of brain maturation.

PMID- 11231225
TI  - MRI in rolandic epilepsy.
AB  - Hippocampal and/or white matter abnormalities have been found on the MRIs in
      10/18 children with typical rolandic epilepsy. The etiology of the first
      mentioned is not evident, whereas the latter may be a result of a maturational
      delay involving a defective myelination. Both abnormalities may cause cognitive
      dysfunction. In order to get a better understanding of rolandic epilepsy both MRI
      and neuropsychological studies are wanted in groups of children with typical
      rolandic seizures with and without rolandic sharp waves, as well as in groups of
      children with typical rolandic sharp waves and atypical seizures.

PMID- 11231226
TI  - Isotope tracer-techniques in rolandic epilepsy and its variants.
AB  - For ethical and practical reasons there are few studies on brain metabolism in
      rolandic epilepsy and it's variants. Most studies are performed in Landau
      Kleffner syndrome or epilepsy with continuous spikes and waves during slow wave
      sleep (CSWS) which are considered to be included within the spectrum of rolandic
      epilepsy. The results of studies using isotope tracer-techniques in rolandic
      epilepsy and its variants are summarized.

PMID- 11231227
TI  - Rolandic epilepsy: neuropsychology of the active epilepsy phase.
AB  - This paper reviews the main studies which have evaluated precisely cognitive
      functions in rolandic epilepsy. There are very few longitudinal data on the
      cognitive evolution of these children, particularly in relationship to the
      paroxysmal electroencephalographic activity. The difficulty to demonstrate direct
      effects of the epileptic EEG discharges on some cognitive functions and on
      learning, as occurs in some cases, is discussed.

PMID- 11231228
TI  - Neuropsychological long-term outcome of rolandic EEG traits.
AB  - BACKGROUND: Long-term outcome of rolandic epilepsy (RE) is associated with a
      diversity of neuropsychological deficits in childhood, although RE is
      historically considered as a benign epileptic disorder. Dyslexia and other
      developmental disorders are associated with rolandic EEG traits. AIM: To
      investigate if there is an association between the manifestation of a specific
      EEG trait of RE and dyslexia. If the EEG traits are causing dyslexia, the
      cognitive deficits are supposed to be normalised after the EEG trait have
      resolved. METHOD: Thirty adolescents and young adults, who had previously
      received a diagnosis of dyslexia by standard criteria, were included. Fifteen
      probands (mean age = 15.9) with dyslexia and rolandic EEG traits were compared
      with 15 age- and sex-matched controls (mean age = 16.0) with normal EEG. RESULTS:
      There were no statistical differences between the groups according to
      intelligence (Verbal IQ, Performance IQ and Arithmetical IQ) or spelling ability.
      However, there was a significant difference between the groups in reading ability
      of non-related words with the group without RE performing better than the group
      with RE (p < 0.01). Attentional shifts in dichotic listening with forced or
      directed attention are generally found in 50-60% in normative samples. However,
      the present date suggest an impaired attentional shift in dichotic listening test
      for both groups. Only one third was able to modulate their ear-preference. There
      were no group differences. CONCLUSION: In general, both dyslectic groups did not
      show significant neuropsychological deficits as compared to standard controls.
      However, there were more reading errors and a tendency to attention impairments
      in the group with rolandic EEG trait as compared to the dyslectic group with
      normal EEG. Possible pathogenic factors are discussed.

PMID- 11231229
TI  - The genetics of rolandic epilepsy.
AB  - Focal spikes and sharp waves with predominantly centrotemporal localization are
      the electroencephalograhic hallmark of Rolandic epilepsy (or BECTS). This EEG
      trait, but not BECTS itself, has been reported to follow an autosomal dominant
      mode of inheritance with incomplete penetrance and age dependency. CTS therefore
      may represent a neurobiological marker for the increased risk of developing
      BECTS. Several linkage studies exploring candidate loci have rendered negative
      results. The first positive evidence for linkage in families with centrotemporal
      spikes was found on chromosome 15q14.

PMID- 11231231
TI  - The case for procedure-specific volume requirements.

PMID- 11231230
TI  - Treatment in typical and atypical rolandic epilepsy.
AB  - Benign rolandic epilepsy is the most common epilepsy of childhood. Regarding
      seizure control typical and atypical rolandic epilepsies have a reasonable
      prognosis. In a recent prospective study STM was shown to control seizures in
      BECTS and STM is regarded as first line drug for this epilepsy in countries
      having access to this drug. Otherwise, CBZ is used most often and very
      effectively in BECTS. However, CBZ has the disadvantage to worsen clinical and
      EEG features up to the precipitation of CSWS in few patients. Epileptic seizures
      are often not the main problem in atypical rolandic epilepsies like CSWS or LKS
      and the amelioration of cognitive dysfunction by epileptic discharge is the
      prominent aim of an AED therapy. Steroids seem the have the best efficacy in
      these cases.

PMID- 11231232
TI  - A new suture for hair transplantation: poliglecaprone 25.
AB  - BACKGROUND: The most common type of donor closure in hair transplantation is with
      nonabsorbable, running sutures, usually of nylon or polypropylene. This is
      accomplished with or without buried absorbable sutures. Another popular method of
      closure is with stainless steel staples. Each of these methods has benefits and
      limitations with respect to healing, comfort, and convenience for the patient.
      OBJECTIVE: The purpose of this study is to describe the use of poliglecaprone 25,
      a synthetic, absorbable, monofilament suture in hair transplantation surgery, to
      detail the suturing techniques needed to maximize the benefit of this suture, and
      to compare this material and suturing technique to a well-established form of
      closure, that of metal staples in a bilaterally controlled fashion. METHODS:
      Poliglecaprone 25 is a synthetic, absorbable monofilament suture of low tissue
      reactivity. It was compared to closure with metal staples in a bilateral
      controlled study. One side of the donor area was closed with poliglecaprone 25
      sutures using a running cutaneous stitch and the other side was closed with
      stainless steel staples. Patients were evaluated with regard to healing,
      postoperative discomfort, resultant surgical scar, and closure material
      preference. RESULTS: Of the 22 patients studied, the following postoperative
      complaints were noted on the staples side: tenderness (12), itching (4), swelling
      (2), and scabbing (1). This compared to only one complaint of itching and one
      complaint of swelling on the poliglecaprone 25 side. Two patients had
      postoperative complaints of visibility of staples showing through their hair.
      Objective measurements revealed a wider scar overall on the staples side in six
      patients and wider scar on the suture side in two patients. The average scar
      width on the staples side measured 1.78 mm compared to 1.42 mm on the suture
      side. Fourteen of the 22 patients preferred poliglecaprone 25 for future
      procedures, 1 preferred metal staples, and 7 had no preference. Most patients
      stated that postoperative discomfort from the staples and the inconvenience and
      occasional pain associated with their removal was responsible for their decision.
      CONCLUSION: Poliglecaprone 25 is a strong synthetic, absorbable, monofilament
      suture with low tissue reactivity that can be used in hair transplantation to
      close the donor wound with a single, running cutaneous stitch. This suture can
      provide a donor closure that ensures hemostasis, has little risk of infection,
      and is comfortable for the patient. If specific surgical techniques are followed,
      this suture can provide a donor closure that ensures hemostasis has little risk
      of complications, is both comfortable and convenient for the patient
      postoperatively and results in a fine surgical scar.

PMID- 11231233
TI  - Tretinoin peeling.
AB  - BACKGROUND: Topical tretinoin has been used for a long time to improve photoaged
      skin, but this therapy takes quite a few months to show some clinical changes.
      Because of that, we think tretinoin peeling would be an excellent choice for
      improvement of photoaged skin. OBJECTIVE: [corrected] Our objective was to show
      the clinical and histologic modifications of the skin after five sessions of
      tretinoin peeling. METHODS: The authors studied the clinical and histologic
      modification that occurred in 15 female patients after conducting tretinoin
      peeling procedures twice a week in concentrations of 1-5%. Conventional
      sectioning of punch biopsy specimens was conducted before and after the
      treatment. RESULTS: Clinical improvement was observed in the skin texture and
      appearance. Through histologic examinations, a decrease in the corneous layer and
      an increase in the epidermal thickness were noticed, inducing an improvement of
      its stratification, as well as the formation of cristae cutis. CONCLUSION: It was
      concluded that the peeling conducted with serial tretinoin showed good clinical
      and histologic results, especially for the treatment of photoaged skins I and II,
      melasma, ephelis, and acne degree I, as well as being practical, quick, and
      easily accomplished with no side effects.

PMID- 11231235
TI  - The S-lift facelift featuring the U-suture and O-suture combined with skin
      resurfacing.
AB  - BACKGROUND: A short-flap S-lift may be helpful for minor jowling or submental
      laxity in cases of early facial ptosis, revision facelifts, or where skin
      resurfacing is combined with neck lifting. OBJECTIVE: To develop a safe and
      effective method to lift the jowl either as a single procedure or combined with
      other rejuvenation methods. METHODS: After the induction of monitored anesthesia
      care the skin resurfacing is completed, if necessary, and the submental and
      lateral S-lift incisions are marked next to the tragus. The submental area is
      hydrodissected with modified tumescent solution. After a 15-minute waiting
      period, the submental area is debulked with small spatula cannulas using reduced
      pressure liposuction. Often the platysma bands are tied together with a running
      locked suture. The right cheek area is hydrodissected and debulked in a similar
      fashion. A 3-4 cm flap is elevated. If necessary, further blunt dissection is
      passed through the anterior mandible ligament and the nasolabial fold. Care is
      taken to keep the skin trabeculae intact. The SMAS is plicated with a U-shaped
      and O-shaped purse-string suture. Following this tightening of the subcutaneous
      tissue, the skin is closed with a double-layer closure. The face is dressed in
      two layers of tube gauze. Sutures are removed in 7-9 days. RESULTS: This S-lift
      gives a pleasing rejuvenation of the jowl and submental area. It is also possible
      to combine this procedure with other procedures such as corset platysmaplasty,
      skin resurfacing, fat augmentation, a browlift, or blepharoplasty. CONCLUSION:
      The S-lift provides a safe and effective method for rejuvenation of the early
      sagging face or for revision facelift.

PMID- 11231234
TI  - Facial nerve injury following superficial temporal artery biopsy.
AB  - BACKGROUND: With proper training, superficial temporal artery biopsy is a safe
      office procedure with few complications. Surgeons from different disciplines,
      including ophthalmologists, dermatologists, general surgeons, and plastic
      surgeons may be called upon to perform this common procedure to confirm giant
      cell arteritis. OBJECTIVE: To emphasize the surgical anatomy of the scalp as it
      pertains to superficial temporal artery biopsy and to raise awareness that
      significant complications can occur after superficial temporal artery biopsy.
      METHOD: Case report. RESULTS: A 75-year-old woman with presumed giant cell
      arteritis developed frontalis muscle paralysis following a superficial temporal
      artery biopsy. Biopsy selection site within the danger zone combined with deep
      dissection carries the greatest risk of injury to the temporal branches of the
      facial nerve. CONCLUSION: Any surgeon involved in the practice of performing
      superficial temporal artery biopsies should have a thorough understanding of
      proper surgical techniques and regional anatomy to avoid potential devastating
      complications.

PMID- 11231236
TI  - Bleomycin in the treatment of keloids and hypertrophic scars by multiple needle
      punctures.
AB  - BACKGROUND: The treatment of keloids and hypertrophic scars has been difficult
      and a recent French study showed that bleomycin has been useful in the treatment
      of these lesions. OBJECTIVE: To determine the effectiveness and safety of
      bleomycin in the treatment of hypertrophic scars and keloids when this drug is
      administered through multiple superficial punctures. METHODS: We applied
      bleomycin to keloids and hypertrophic scars in 13 patients using a multiple
      puncture method on the surface of the skin. All patients were given bleomycin at
      a concentration of 1.5 IU/ml. Clinical response after treatment was classified
      according to the following scale: complete flattening (100%), highly significant
      flattening (>90%), or significant flattening (75-90%). RESULTS: The clinical
      response was very positive in all cases: complete flattening in six cases, highly
      significant flattening in six cases, and significant flattening in one case. Two
      patients presented a recurrence as a small nodule 10 and 12 months after the last
      infiltration. CONCLUSIONS: These clinical findings show that administration of
      bleomycin in keloids and hypertrophic scars shows promise and needs further
      investigation.

PMID- 11231237
TI  - Temporary tattooing followed by Q-switched alexandrite laser for treatment of
      syringomas.
AB  - BACKGROUND: Syringomas usually develop in women as multiple skin-colored papules
      primarily seen on the periocular regions and cheeks. They can cause cosmetic
      problems and lead to poor self-esteem. Though several treatment modalities have
      been established, such as excision, electro/cryosurgery, chemical peeling, and
      CO2 laser surgery, none of them are satisfactory due to their limitations and
      side effects, for example, pain, prolonged healing time, postoperative
      erythema/pigmentary changes, and scarring. OBJECTIVE: The objective of this study
      was to develop a new treatment method for syringoma and to minimize the side
      effects through selective destruction of the tumor. METHODS: Six patients with
      multiple periorbital syringomas were enrolled in this study. The surface
      epithelium of the syringomas was vaporized by CO2 laser, and black ink was
      introduced in order to allow penetration to the dermis using iontophoresis.
      Subsequently the artificial tattoos were removed by Q-switched alexandrite laser.
      The results were evaluated clinically by both physicians and patients at 1, 2, 4,
      and 8 weeks after treatment. RESULTS: The majority of syringoma in the six
      patients disappeared by the first follow-up 1 week after treatment. There were no
      cases of prolonged erythema persisting beyond 2 weeks. Additional treatment was
      repeated in the same manner in order to remove the remaining syringomas in one
      patient. There were no recurrences during the 8-week follow-up period.
      CONCLUSION: Our new treatment was safer, less painful, nonscarring, and there was
      a quicker recovery period and less of a burden to repeat treatment when
      necessary.

PMID- 11231238
TI  - Clinical characteristics of 500 consecutive patients presenting for laser removal
      of lower extremity spider veins.
AB  - BACKGROUND: Laser treatment for removal of lower extremity spider veins is
      emerging as a modality of choice in patients with small spider veins, those who
      have previously undergone sclerotherapy or vein stripping, and those refusing
      sclerotherapy. OBJECTIVE: To determine clinical characteristics of patients
      presenting for laser treatment of leg veins. METHODS: The clinical
      characteristics of 500 patients presenting for laser treatment of spider veins
      were evaluated to investigate characteristics leading to their development, and
      to characterize the type of patients presenting for laser treatment. RESULTS:
      Patients presenting for treatment range widely in age and have had spider veins
      for an average of 14 years. Both pregnancy and previous sclerotherapy were
      factors that contributed to the development or exacerbation of spider veins.
      CONCLUSION: As laser treatment of spider veins improves, this modality will play
      an increasing role in the management of lower extremity telangiectasias.

PMID- 11231240
TI  - An effective treatment of dark lip by frequency-doubled Q-switched Nd:YAG laser.
AB  - BACKGROUND: Dark lip is a common cosmetic problem in Southeast Asia. There is no
      known effective treatment. OBJECTIVE: To propose an effective method for treating
      dark lips of varying causes with frequency-doubled Q-switched Nd:YAG laser.
      METHODS: Seventy patients with dark lip, of which 22 were congenital, 24
      acquired, and 24 of uncertain cause, were treated by frequency-doubled Q-switched
      Nd:YAG laser at a fluence of 2-3.5 J/cm2 (mode 2.5 J/cm2) after application of
      topical anesthesia. The endpoint of treatment was complete clearance of the
      pigment. Follow-up time was 24-36 months (mean 29 months). RESULTS: All patients
      attained complete clearance of the lesion after an average of 2.5 treatments in
      the congenital group, 2.2 treatments in the acquired group, and 1.8 treatments in
      the group with uncertain etiology. The mean (+/-SD) number of treatments required
      by the whole group was 2.1 +/- 1.4. Recurrence was observed in one case of
      congenital origin 3 months after the last treatment. In the remaining cases,
      results persisted up to the time of follow-up. Herpes simplex reactivation was
      noted in one case 3 days after treatment. There was no dyschromia, scar
      formation, or change of skin texture. CONCLUSION: Dark lip can be effectively
      treated by frequency-doubled Q-switched Nd:YAG laser without major adverse
      effects.

PMID- 11231239
TI  - Improving botulinum toxin therapy for palmar hyperhidrosis: wrist block and
      technical considerations.
AB  - Botulinum A exotoxin has become an excellent therapeutic option to treat focal
      hyperhidrosis, but when the problem affects the palmar region the technique has
      some drawbacks. Pain with injection is difficult to tolerate and the large dose
      needed to treat both hands are two concerns, as well as muscle weakness secondary
      to botulinum toxin diffusion and the possibility of antibody production. All
      these problems limit the number of patients treated. The author's suggestion is
      to treat only the dominant hand, after performing a wrist block. The use of a
      device adapted from a cartridge rubber may help to control the injection depth
      and the risk of muscular weakness.

PMID- 11231241
TI  - Pincer nails: a new surgical treatment.
AB  - BACKGROUND: Pincer nails are a kind of nail deformity characterized by a
      transverse overcurvature of the nail that increases along the longitudinal axis.
      Alteration of the shape of the underlying distal phalanx due to osteophyte
      formation at the apex may be a cause of pincer nails. This causes widening of the
      proximal matrix and as a result secondary torque in the distal nail plate leading
      to the typical appearance. Apart from conservative treatment, several surgical
      techniques have been proposed in the past. METHODS: This article presents a new
      surgical approach in the treatment of recalcitrant pincer nails which has several
      distinct advantages over other methods. RESULTS: Long-term results in six
      patients are presented.

PMID- 11231242
TI  - The use of the V-Y fasciocutaneous island advancement flap in reconstructing
      postsurgical defects of the leg.
AB  - BACKGROUND: Soft tissue cover in the lower limb is difficult due to limited
      tissue mobility. OBJECTIVE: To present the V-Y fasciocutaneous island advancement
      flap as an alternative for reconstructing postsurgical defects of the leg.
      METHODS: Eleven patients with defects on the leg following tumor excision were
      reconstructed using the V-Y fasciocutaneous island advancement flap. RESULTS:
      There were no major complications, except for one partial distal flap necrosis in
      a patient who was a smoker. CONCLUSION: The V-Y fasciocutaneous island
      advancement flap is a viable alternative for reconstructing surgical defects of
      the leg.

PMID- 11231243
TI  - Delayed-type hypersensitivity and cross-reactivity to heparins and danaparoid: a
      prospective study.
AB  - BACKGROUND: Delayed-type hypersensitivity (DTH) reactions in patients receiving
      heparin may occur with both unfractionated (UFHs) and low molecular weight
      heparins (LMWHs). Skin testing is a clue to detect tolerated heparin or
      heparinoid preparations for further treatment. OBJECTIVE: To study in vivo cross
      reactivity between LMWHs, UFHs, and danaparoid by skin testing in patients with
      suspected DTH to heparin. METHODS: Patients who fulfilled the criteria for the
      diagnosis of suspected heparin allergy were involved in a prospective study after
      informed consent. Patients presented with or had a history of typical
      erythematous plaques at the heparin injection sites. Skin testing was performed
      by subcutaneous injections of heparin (300-500 IU anti-Xa activity) and
      danaparoid (375 IU, eight patients). Desirudin (27,000 IU) was tested in three
      patients. We read skin reactions after 24, 48, and 96 hours and after 7 days.
      RESULTS: Fourteen female and 4 male patients were included in our series.
      Erythematous plaques had been reported or developed after 14-35 days in patients
      during first-time heparin treatment and after 2-10 days in reexposed patients.
      Positive skin test results were seen in 15 of 18 (83.3%) patients. Of these, 11
      (73.3%) showed cross-reactivity between heparins and/or danaparoid. Six patients
      reacted to LMWHs only, nine patients to both LMWHs and UFHs. Danaparoid was
      tolerated in six of eight patients; desirudin was tolerated in all three patients
      tested. CONCLUSIONS: DTH to heparins is characterized by considerable cross
      reactivity between LMWHs, UFHs, and danaparoid. UFHs may be tolerated even if
      LMWHs are not. Subcutaneous testing of a panel of heparins, danaparoid, and
      desirudin (hirudin) is recommended to determine acceptable treatment options for
      patients allergic to specific heparins.

PMID- 11231244
TI  - Incidence of female androgenetic alopecia (female pattern alopecia).
AB  - BACKGROUND: Female pattern alopecia seems to be increasing. A recent article
      suggests that female androgenetic alopecia may not be androgen dependent and is a
      different entity than male androgenetic alopecia. OBJECTIVE: To determine the
      incidence at different ages of female androgenetic alopecia in 1000 Caucasian
      women 20 years of age and older. METHODS: A total of 1006 Caucasian women were
      examined for the presence of female androgenetic alopecia. CONCLUSION: Female
      androgenetic alopecia is quite common beginning in the late 20s and reaching its
      peak after 50 years of age.

PMID- 11231245
TI  - A new surgical therapeutic approach to pincer nail deformity.
AB  - BACKGROUND: Pincer nail deformity (PND) is an important health problem that
      causes discomfort in daily life. Until now, some surgical and conservative
      treatment modalities were applied with success. However, there is still no
      consensus on the common and accepted form of treatment. OBJECTIVE: To present a
      new surgical therapeutic approach to PND. METHODS: Ten patients, four with
      bilateral and six with unilateral PND, were treated with a new surgical technique
      which is a combination of chemical matricectomy with phenol and nail bed repair.
      RESULTS: No recurrence was observed in any of the patients after 12-16 months
      follow-up. No serious complication was encountered. The cosmetic improvement was
      also marked and satisfactory. CONCLUSION: This new surgical approach was found to
      be effective and is presented as an alternative treatment modality for PND.

PMID- 11231246
TI  - Preliminary experience with a new sclerosing foam in the treatment of varicose
      veins.
AB  - BACKGROUND: Recently a new method of using a foam sclerosing agent for the
      treatment of leg veins has been described. We present a pilot study of a new
      technique for producing the sclerosing foam (Tessari's method) (SFT) and its use
      in sclerotherapy of major and minor varicosities. OBJECTIVE: A preliminary
      multicenter experience of sclerotherapy performed by means of this new kind of
      sclerosing foam made of purified sodium tetradecylsulfate is described. The
      authors evaluated the safety and efficacy of different doses and concentrations
      of the drug as well as different methods of preparing the foam in addition, the
      results of this technique were evaluated. METHODS: Over a 6-week period the three
      authors performed sclerotherapy or duplex-guided sclerotherapy using SFT,
      treating 77 patients. The SFT was formed using a three-way stopcock and two
      syringes, mixing air with liquid sodium tetradecylsulfate to create a foam. Each
      author used different concentrations (0.1-3%) and doses (2-8 ml) of SFT according
      to the size and number of the veins. Alternate methods of preparing the foam were
      examined as well. Seventy percent of the sclerotherapy sessions were performed on
      either the long or short saphenous veins, recurrent varices, or collaterals.
      Thirty percent of the treatments were for reticular varices and telangiectases.
      RESULTS: At 1-month follow-up, the vast majority of treated larger veins were
      either obliterated or showed a normal state of cephalad blood flow. Results for
      minor varicosities were good, but with related complications of hyperpigmentation
      and small areas of cutaneous necrosis. Two patients experienced transient
      scotomas and one patient developed segmental phlebitis of a collateral vein. The
      best foam was obtained by mixing one part liquid sodium tetradecylsulfate and
      four to five parts air, but the duration of the foam product was also related to
      several other factors. CONCLUSION: This preliminary pilot study demonstrates that
      the technique of producing sclerosing foam according to Tessari's method (three
      way stopcock device) is very promising, especially for larger veins. No serious
      complications were reported, and further standardization of the method may
      improve the results and feasibility of this technique. Further studies are needed
      to validate this new technique.

PMID- 11231247
TI  - The apical angle: a mathematical analysis of the ellipse.
AB  - BACKGROUND: The elliptical excision is a common surgical procedure. The
      dermatologic literature predominantly describes an excisional geometry with a 3:1
      length:width ratio and an apical angle of 30 degrees. OBJECTIVE: To analyze the
      elliptical excision by applying mathematical principles and define the apical
      angle and its relationship to the length:width ratio. METHODS: We examined
      numerous examples of elliptical excisions as presented in the dermatologic
      literature. We analyzed the geometry of the excisions and defined it
      mathematically. RESULTS: The apical angle of a 3:1 elliptical excision is not 30
      degrees. The true apical angle varies from 37 degrees to 74 degrees depending on
      excisional geometry. CONCLUSION: The commonly presented apical angle of 30
      degrees is incorrect and does not reflect the true apical angle of elliptical
      excisions.

PMID- 11231248
TI  - Series spiral advancement flap: an alternative to the ellipse.
AB  - BACKGROUND: Surgical excision of skin lesions is a common dermatologic procedure.
      OBJECTIVE: An alternative to the elliptical excision is described. METHODS: We
      present an excisional technique that creates a series of nonepidermal outwardly
      spiraling flaps. The surgical defect is closed with specially tunneled absorbable
      suture. RESULTS: There has been no increase in infectious complications or wound
      failures compared with standard ellipses. Proper patient and lesion selection
      aids in obtaining an acceptable outcome. CONCLUSION: The series spiral
      advancement flap has the potential to become a useful and common surgical
      technique.

PMID- 11231249
TI  - Malignant eccrine spiradenoma: a case report and review of the literature.
AB  - BACKGROUND: Eccrine spiradenoma is a well-differentiated benign tumor of the
      sweat glands. Malignant change arising within eccrine spiradenoma is rare.
      OBJECTIVE: We describe a patient with malignant eccrine spiradenoma exhibiting
      both carcinomatous and sarcomatous differentiation. METHODS: Case report and
      literature review. RESULTS: A 37-year-old woman noted enlargement of a left
      axillary tumor that had been present for 20 years. The tumor was resected and the
      specimen, measuring 3.0 cm x 1.5 cm, revealed an encapsulated benign eccrine
      spiradenoma as well as an undifferentiated carcinoma possessing both
      carcinomatous and sarcomatous components. A transition zone was evident between
      the benign eccrine spiradenoma and the undifferentiated carcinoma, suggesting
      that the latter had arisen from the benign tumor. The malignant areas consisted
      principally of undifferentiated carcinoma (70%), although squamous cell carcinoma
      (10%), adenocarcinoma (10%), and chondrosarcomatous (10%) components were also
      present. Numerous mitotic figures were noted within the areas of malignant
      change, suggesting that the tumor was aggressive in nature. The patient died of
      systemic metastases 7 months after diagnosis. CONCLUSION: Although eccrine
      spiradenomas are usually benign, they can, on rare occasions, undergo malignant
      transformation. This case report describes one such occurrence of malignant
      transformation of a benign eccrine spiradenoma that unfortunately resulted in the
      patient's death from systemic metastases 7 months after diagnosis.

PMID- 11231250
TI  - Effective management of difficult surgical defects using tissue-engineered skin.
AB  - BACKGROUND: Graftskin, a bilayered living skin construct, is an effective
      therapeutic option in the management of chronic venous ulcerations and simple
      acute surgical excisions. However, it is not routinely used in the management of
      complicated surgical wound defects. OBJECTIVE: To determine the effectiveness of
      graftskin as a therapeutic modality in difficult surgical defects. METHODS: Two
      patients with complex surgical wound defects after Mohs micrographic surgery
      underwent a single application of graftskin. The engineered skin was fenestrated
      and sutured in place. The wounds were examined on a weekly basis. One hundred
      percent healing was defined as complete reepithelialization (wound coverage).
      RESULTS: Graftskin was well tolerated by these patients and resulted in complete
      wound healing within 9 weeks of application. CONCLUSION: Graftskin is an
      excellent alternative for difficult surgical wounds not amenable to other
      therapies. Graftskin results in a shortened healing time and decreased morbidity.
      It should be considered for wounds in which healing by secondary intention is
      preferably avoided.

PMID- 11231251
TI  - Undermining in cutaneous surgery.
AB  - BACKGROUND: Benefits, risks, and technical aspects of undermining in cutaneous
      surgery are presented and reviewed in order to facilitate the execution of this
      fundamental task of cutaneous surgery. METHODS: The authors' extensive experience
      with thousands of cutaneous reconstructions and literature consultation form the
      basis of this review. RESULTS: Literature review and practical experience
      indicate that undermining reduces wound closing tension. Pertinent anatomic
      considerations, benefits, risks, as well as sharp and blunt undermining
      techniques and regional undermining recommendations are discussed. CONCLUSIONS:
      It is concluded that judicious undermining, properly performed by surgeons
      knowledgeable of cutaneous anatomy facilitates the execution and enhances
      cosmesis in cutaneous reconstruction. It is the authors' opinion that sharp
      undermining technique is the optimal method for most cutaneous reconstructions.

PMID- 11231252
TI  - Applications of the double O to Z flap repair for facial reconstruction.
AB  - Multiple defects are often encountered in the treatment of malignant skin tumors.
      Nearby defects can present a reconstructive challenge since the closure of one
      defect may impact the closure of the other defect. The double O to Z flap design
      is ideally suited to combine the closure of adjacent defects into one technique.
      This flap technique and design is illustrated and described. Examples include
      defects on the forehead, temple, cheek, and nose following Mohs micrographic
      surgery.

PMID- 11231253
TI  - Reconstruction of a large surgical defect on the nasal tip and ala.

PMID- 11231254
TI  - Lessons on dermoscopy #12. Malignant melanoma in situ with regression.

PMID- 11231255
TI  - Why use a digital camera system?

PMID- 11231256
TI  - Trelles-Jaeger lid plate.

PMID- 11231257
TI  - Regarding the multilayer technique for treatment of PWS.

PMID- 11231258
TI  - Regarding postoperative stroke after warfarin for cutaneous surgery.

PMID- 11231259
TI  - Suction device employing a syringe and a manometer: not so new.

PMID- 11231261
TI  - Delayed wound healing after laser resurfacing.

PMID- 11231262
TI  - Regarding sentinel node biopsy in the management of melanoma.

PMID- 11231263
TI  - Inexpensive liquid nitrogen container.

PMID- 11231264
TI  - Reducing pain during hair transplant lidocaine infiltration.

PMID- 11231265
TI  - Facial tumescent solution for cryosurgery: subtract the epinephrine, add a
      steroid, and avoid spinal needles.

PMID- 11231266
TI  - Effects of mutations in mitochondrial cytochrome b in yeast and man. Deficiency,
      compensation and disease.
AB  - The mitochondrial cytochrome bc(1) complex is a key protonmotive component of
      eukaryotic respiratory chains. The mitochondrially encoded cytochrome b forms,
      with cytochrome c(1) and the iron--sulfur protein, the catalytic core of this
      multimeric enzyme. Mutations of cytochrome b have been reported in association
      with human diseases. In the highly homologous yeast cytochrome b, several
      mutations that impair the respiratory function, and reversions that correct the
      defect, have been described. In this paper, we re-examine the mutations in the
      light of the atomic structure of the complex, and discuss the possible effect, at
      enzyme level, of the human cytochrome b mutations and the correcting effect of
      the reversions.

PMID- 11231267
TI  - Factors affecting the dimerization of the p66 form of HIV-1 reverse
      transcriptase.
AB  - The association and dissociation of the homodimeric p66/p66 form of HIV-1 reverse
      transcriptase were investigated. The effects on the dimerization process of
      different salt concentrations, pH and the presence of a template/primer and
      nucleotide substrates were monitored by measuring polymerase activity and
      analytical size-exclusion HPLC. At submicromolar concentrations of enzyme and
      physiological salt concentrations, most of the enzyme exists in the inactive
      monomeric form. Increasing NaCl concentration from 0.05 to 1 M decreased the
      equilibrium dissociation constant from 2.0 to 0.34 microM. Analysis of the
      kinetics of the dimerization process indicated it followed a two-step mechanism,
      with rapid initial association of the two subunits to form an inactive homodimer
      followed by a slow isomerization step rendering the active enzyme form. The
      presence of poly(rA)/dT(20) decreased the equilibrium dissociation constant of
      the homodimer about 30-fold, while the addition of 5 microM dTTP had no effect.
      The kinetics of the process showed that the template/primer favored dimerization
      by binding to the inactive homodimer and promoting its isomerization to the
      active form. These results were confirmed by analyzing the reverse reaction, i.e.
      the dissociation of the enzyme, by dilution in a low-ionic-strength buffer. The
      results suggest that binding of immature HIV-1 reverse transcriptase to its
      natural template/primer may be relevant in both the dimerization process and the
      selection of its natural primer.

PMID- 11231268
TI  - Construction, separation and properties of hybrid hexamers of glutamate
      dehydrogenase in which five of the six subunits are contributed by the
      catalytically inert D165S.
AB  - In vitro subunit hybridization was used to explore the basis of putative
      allosteric behaviour in clostridial glutamate dehydrogenase. C320S and D165S
      mutant enzymes were chosen to construct the hybrid proteins. The C320S mutant
      protein is fully active and shows normal allosteric properties but lacks the
      reactive cysteine. D165S is capable of binding both glutamate and NAD(+) but is
      catalytically inactive. The mutant proteins were denatured separately in 4 M
      urea, mixed in a 5 : 1 (D165S/C320S) ratio and diluted into a refolding mixture
      composed of 2 mM NAD(+), 1 M fluoride and artificial chaperones (4 mM
      polyoxyethylene 10 lauryl ether and 1.6 mM beta-cyclodextrin). Under these
      conditions approximately 50% refolding was achieved for both mutant proteins
      separately. The renatured mixture was concentrated and separated from denatured
      proteins and the components of the refolding mixture by ultrafiltration and ion
      exchange chromatography. Ellman's reagent, 5,5'-dithiobis (2-nitrobenzoic acid)
      (DTNB), which binds close to the NAD(+) binding site, thus abolishing coenzyme
      binding in the wild-type enzyme, also reacts with D165S but has no effect on
      C320S. Modification by DTNB was coupled with dye-ligand affinity chromatography
      on a Procion Red HE-3B column in order to separate the hybrid mixture into
      fractions of defined composition. An optimized procedure based on salt gradient
      elution was developed. DTNB-modified 5 : 1 hybrids, with only one subunit capable
      of binding coenzyme, showed classical Michaelis-Menten kinetics when the NAD(+)
      concentration was varied, whereas removal of the thionitrobenzoate moieties that
      blocked the other five coenzyme binding sites in the hexamer reinstated nonlinear
      behaviour, suggesting that 'nonlinear' behaviour of the native enzyme and the
      hybrid with six coenzyme binding sites depends on binding to multiple sites. When
      assayed at high pH with increasing glutamate concentration, the sample with only
      one active subunit showed reduced sigmoidicity in the dependence of reaction rate
      on glutamate concentration (h = 3.0) compared with native C320S with six active
      subunits (h = 5.2) suggesting that the interaction between the subunits was
      reduced but not abolished completely. Catalytically silent subunits can thus
      still contribute to cooperativity.

PMID- 11231269
TI  - Characterization of oligosaccharides from the chondroitin sulfates. (1)H-NMR and
      (13)C-NMR studies of reduced disaccharides and tetrasaccharides.
AB  - Chondroitin sulfates were fragmented using the enzymes chondroitin sulfate ABC
      endolyase and chondroitin ACII lyase; both disaccharide and tetrasaccharide
      fragments were isolated after reduction to the corresponding 2-deoxy-2-N
      acetylamino-D-galactitol (GalNAc-ol) form. These have the structures: Delta
      UA(beta 1--3)GalNAc4S-ol, Delta UA(beta 1--3)GalNAc6S-ol, Delta UA2S(beta 1-
      3)GalNAc6S-ol, Delta UA(beta 1--3)GalNAc4S(beta 1--4)L-IdoA(alpha 1--3)GalNAc4S
      ol, Delta UA(beta 1--3)GalNAc4S(beta 1--4)GlcA(beta 1--3)GalNAc4S-ol, Delta
      UA(beta 1--3)GalNAc6S(beta 1--4)GlcA(beta 1--3)GalNAc4S-ol, Delta UA(beta 1-
      3)GalNAc6S(beta 1--4)GlcA(beta 1--3)GalNAc6S-ol, Delta UA2S(beta 1-
      3)GalNAc6S(beta 1--4)GlcA(beta 1--3)GalNAc4S-ol and Delta UA2S(beta 1-
      3)GalNAc6S(beta 1--4)GlcA(beta 1--3)GalNAc6S-ol, where Delta UA represents a 4,5
      unsaturated hexuronic acid (4-deoxy-alpha-Lthreo-hex-4-enepyranosyluronic acid)
      and 6S/4S/2S represent O-ester sulfate groups at C6/C4/C2 sites. Complete (1)H
      NMR and (13)C-NMR data are derived for these species, which may help to alleviate
      some of the significant difficulties resulting from signal complexity that are
      currently hindering the characterization and assignment of major and minor
      structural components within chondroitin sulfate and dermatan sulfate polymers.

PMID- 11231270
TI  - Glycoinositolphosphosphingolipids (basidiolipids) of higher mushrooms.
AB  - The basidiolipids of six mushroom species, i.e. the basidiomycetes Amanita virosa
      (engl., death cup), Calvatia exipuliformis (engl., puffball), Cantharellus
      cibarius (engl., chanterelle), Leccinum scabrum (engl., red birch boletus),
      Lentinus edodes (jap., Shiitake), and Pleurotus ostreatus (engl.,
      oystermushroom), were isolated, and their chemical structures investigated. All
      glycolipids are structurally related to those of the Agaricales (engl., field
      mushroom). They are glycoinositolphosphosphingolipids, their ceramide moiety
      consisting of t18:0-trihydroxysphinganine and an alpha-hydroxy long-chain fatty
      acid. In contrast to a previous study [Jennemann, R., Bauer, B.L., Bertalanffy,
      H., Geyer, R., Gschwind, R.M., Selmer, T. & Wiegandt, H. (1999) Eur. J. Biochem.
      259, 331--338], the glycoside anomery of the hexose (mannose) connected to the
      inositol of all investigated basidiomycete glycolipids, including the
      basidiolipids of Agaricus bisporus, was determined unequivocally to be alpha.
      Therefore, the root structure of all basidiolipids consists of alpha-DManp-2Ins1
      [PO(4)]-Cer. In addition, for some mushroom species, the occurrence of an
      inositol substitution position variant, alpha-Manp-4Ins1-[PO(40]-Cer, is shown.
      The carbohydrate of chanterelle basidiolipids consists solely of mannose, i.e.
      Cc1, Man alpha-3 or -6Man alpha; Cc2, Man alpha-3(Man alpha-6)Man alpha-. All
      other species investigated show extension of the alpha-mannoside in the 6
      position by beta-galactoside, which, in some instances, is alpha-fucosylated in 2
      position (Fuc alpha-2)Gal beta-6Man alpha-. Further sugar chain elongation at the
      beta-galactoside may be in 3- and/or 6-position by alpha-galactoside, e.g. Ce4,
      Po2, Gal alpha-3-(Gal alpha-6)(Fuc alpha-2)Gal beta-6Man alpha-, whereas A.
      virosa, Av-3, has a more complex, highly alpha-fucosylated terminus, Gal alpha-3
      (Fuc alpha-2)(Fuc alpha-6)Gal alpha-2(Gal alpha-3)Gal beta-6Man alpha-. L. edodes
      basidiolipids show further elongation by alpha-mannoside, e.g. Le3, Man alpha
      2Man alpha-6Gal alpha-3(Fuc alpha-2)Gal beta-6Man alpha-, C. exipuliformis
      glycolipid by alpha-glucoside, i.e. Ce3, Glc alpha-6Gal beta-6Man alpha-.
      Basidiolipid Ls1 from L. scabrum, notably, has a 3-alpha-mannosylated alpha
      fucose, i.e. Gal alpha-6(Man alpha-3Fuc alpha-2)Gal alpha-6Gal beta-6Man alpha-.
      In conclusion, basidiolipids, though identical in their ceramide constitution,
      display wide and systematic mushroom species dependent variabilities of their
      chemical structures.

PMID- 11231271
TI  - S1 subsite specificity of a recombinant cysteine proteinase, CPB, of Leishmania
      mexicana compared with cruzain, human cathepsin L and papain using substrates
      containing non-natural basic amino acids.
AB  - We have explored the substrate specificity of a recombinant cysteine proteinase
      of Leishmania mexicana (CPB2.8 Delta CTE) in order to obtain data that will
      enable us to design specific inhibitors of the enzyme. Previously we have shown
      that the enzyme has high activity towards substrates with a basic group at the P1
      position [Hilaire, P.M.S., Alves, L.C., Sanderson, S.J., Mottram, J.C., Juliano,
      M.A., Juliano, L., Coombs, G.H. & Meldal M. (2000) Chem. Biochem. 1, 115--122],
      but we have also observed high affinity for peptides with hydrophobic residues at
      this position. In order to have substrates containing both features, we
      synthesized one series of internally quenched fluorogenic peptides derived from
      the sequence ortho-amino-benzoyl-FRSRQ-N-[2,4-dinitrophenyl]-ethylenediamine, and
      substituted the Arg at the P1 position with the following non-natural basic amino
      acids: 4-aminomethyl-phenylalanine (Amf), 4-guanidine-phenylalanine (Gnf), 4
      aminomethyl-N-isopropyl-phenylalanine (Iaf), 3-pyridyl-alanine (Pya), 4
      piperidinyl-alanine (Ppa), 4-aminomethyl-cyclohexyl-alanine (Ama), and 4
      aminocyclohexyl-alanine (Aca). For comparison, the series derived from ortho
      amino-benzoyl-FRSRQ-N-[2,4-dinitrophenyl]-ethylenediamine was also assayed with
      cruzain (the major cysteine proteinase of Trypanosoma cruzi), human cathepsin L
      and papain. The peptides ortho-amino-benzoyl-FAmfSRQ-N-[2,4-dinitrophenyl]
      ethylenediamine (k(cat)/K(m) = 12,000 mM(-1) x s(-1)) and ortho-amino-benzoyl
      FIafSRQ-N-[2,4-dinitrophenyl]-ethylenediamine (k(cat)/K(m) = 27,000 mM(-1) x s(
      1)) were the best substrates for CPB2.8 Delta CTE. In contrast, ortho-amino
      benzoyl-FAmaSRQ-N-[2,4-dinitrophenyl]-ethylenediamine and ortho-amino-benzoyl
      FAcaSRQ-N-[2,4-dinitrophenyl]-ethylenediamine were very resistant and inhibited
      this enzyme with K(i) values of 23 nM and 30 nM, respectively. Cruzain hydrolyzed
      quite well the substrates in this series with Amf, Ppa and Aca, whereas the
      peptide with Ama was resistant and inhibited cruzain with a K(i) of 40 nM. Human
      cathepsin L presented an activity on these peptides very similar to that of
      CPB2.8 Delta CTE and papain hydrolyzed all the peptides with high efficiency. In
      conclusion, we have demonstrated that CPB2.8 Delta CTE has more restricted
      specificity at the S1 subsite and it seems possible to design efficient
      inhibitors with amino acids such as Ama or Aca at the P(1) position.

PMID- 11231272
TI  - Structure, localization and potential role of a novel molluscan trypsin inhibitor
      in Lymnaea.
AB  - Eggs and egg masses of the freshwater gastropod mollusc Lymnaea provide a
      microenvironment for developing embryos. Secretions of the exocrine albumen gland
      of Lymnaea are packaged in the eggs of an egg mass before the eggs are laid
      externally. The perivitelline fluid that directly surrounds individual oocytes is
      the main source of nutrition for developing embryos. During early stages of
      development, the perivitelline fluid is initially internalized by pinocytosis and
      degraded by lysosomes; in later stages, the embryo ingests the fluid. We
      previously found that the albumen gland produces large amounts of Lymnaea
      epidermal growth factor. The albumen gland also appears to produce significant
      amounts of a novel Lymnaea trypsin inhibitor (LTI), a second peptide that was
      purified and characterized from Lymnaea albumen gland extracts. The primary
      structure was determined by microsequence analysis, mass spectrometry, and C
      terminal sequence analysis, and showed that LTI is a 57-residue glycosylated
      peptide. Comparison of the LTI sequence with other known serine protease
      inhibitors indicates that LTI is a member of the bovine pancreatic trypsin
      inhibitor family. Reverse phase-high performance liquid chromatography,
      microsequence analysis, mass spectrometry, and immunocytochemistry demonstrated
      that abundant amounts of intact LTI are packaged in egg masses. The presence of a
      trypsin inhibitor in the perivitelline fluid compartment of the egg mass may
      minimize digestion of peptides and proteins in the perivitelline fluid that are
      important for the development of the embryo, for example, Lymnaea epidermal
      growth factor.

PMID- 11231273
TI  - Chromatin structure of the bovine Cyp19 promoter 1.1. DNaseI hypersensitive sites
      and DNA hypomethylation correlate with placental expression.
AB  - Expression of the Cyp19 gene, encoding aromatase cytochrome P450, is driven by
      several tissue-specific promoters. The underlying mechanisms of this complex
      regulation have not yet been elucidated in detail. In the present report we
      investigate a possible link between chromatin structure and tissue-specific
      regulation of the bovine Cyp19 gene. We analysed the DNA methylation status and
      mapped DNaseI hypersensitive sites in the region encompassing the Cyp19 promoter
      1.1 (P1.1) which controls Cyp19 expression in the bovine placenta. We show that
      P1.1 is hypomethylated in placental cotyledons (foetal layer) whereas it is
      methylated in placental caruncles (maternal layer), testis and corpus luteum.
      Furthermore, two placenta-specific DNaseI hypersensitive sites, HS1 and HS2, were
      observed within P1.1. Both DNA hypomethylation and the presence of DNaseI
      hypersensitive sites correlate with transcriptional activity of P1.1. Sequence
      analysis of hypersensitive sites revealed potential cis-regulatory elements, an E
      box in HS1 and a trophoblast-specific element-like sequence in HS2. It could be
      demonstrated by electrophoretic mobility shift assays that both sequence motifs
      are specific targets for placenta-derived nuclear factors. In conclusion,
      observed tissue-specific differences of the chromatin structure which correlate
      with tissue-specific promoter activity suggest that chromatin might be an
      important regulator of aromatase expression in cattle.

PMID- 11231274
TI  - A comparative study of the asparagine-linked oligosaccharides on siglec-5, siglec
      7 and siglec-8, expressed in a CHO cell line, and their contribution to ligand
      recognition.
AB  - The siglecs (sialic acid-binding immunoglobulin-like lectins) mediate sialic acid
      dependent cellular interactions and may in some cases signal through SH2-binding
      domains. In addition to the previously characterized siglecs, sialoadhesin, CD22,
      CD33 and myelin-associated glycoprotein, several new ones, siglec-5, siglec-7 and
      siglec-8, have recently been cloned. Although these novel receptors have
      generated considerable interest as therapeutic targets because of their
      expression pattern on immune cells, very little is known about how their lectin
      activity is regulated. Previous studies with sialoadhesin, CD22 and CD33 have
      shown that siglec glycosylation has significant effects on binding. To determine
      any differences in the glycan composition of siglec-5, siglec-7 and siglec-8 that
      may modify their function, we released and characterized the N-linked
      oligosaccharide distribution in these three glycoproteins. The glycan pools from
      siglec-5 and siglec-7 contained a larger proportion of sialylated and core
      fucosylated biantennary, triantennary and tetra-antennary oligosaccharides,
      whereas the carbohydrate mixture released from siglec-8 is noticeably less
      sialylated and is more abundant in 'high-mannose'-type glycans. In addition, we
      show that, in contrast with CD22 and CD33, mutating the conserved potentially N
      linked glycosylation site in the first domain has no effect on binding mediated
      by siglec-5 or siglec-7.

PMID- 11231275
TI  - Phosphoinositide fatty acids regulate phosphatidylinositol 5-kinase,
      phospholipase C and protein kinase C activities.
AB  - PtdIns(4,5)P(2) generally results from phosphorylation of PtdIns(4)P by the
      phosphatidylinositol 5-kinase (PtdIns5-K). Its hydrolysis by phospholipase C
      (PLC) yields inositol 1,4,5-trisphosphate and diacylglycerol, which stimulates
      protein kinase C (PKC). We show that epithelial cells of the cockroach rectum
      contain three different inositol lipids: PtdIns(4,5)P(2), PtdIns(4)P, and PtdIns.
      They are composed of six major fatty acids: palmitic (16:0) stearic (18:0), oleic
      (18:1n--9), linoleic (18:2n--6), linolenic (18:3n--3), and arachidonic (20:4n-6)
      acids. The fatty acid preference of each of the above enzymes was evaluated by
      incorporating different fatty acids in pairs into membrane lipids. Incorporation
      of 16:0 plus 18:1n--9 provoked an increase in PtdIns(4,5)P2-PLC activity and a
      decrease in PtdIns5-K activity. In contrast, incorporation of 16:0 plus 18:3n--3
      led to a potentiation of PtdIns5-K activity and a decrease in PtdIns(4,5)P(2)-PLC
      activity. Furthermore, PLC and PtdIns5-K acted preferentially on substrates
      containing 18:3n--3, and 18:3n--3-containing diacylglycerol specifically
      potentiated PKC activity. Thus, we propose that the fatty acids that make up the
      phosphoinositides function as intracellular modulators of the activity of certain
      enzymes.

PMID- 11231276
TI  - Organization and chromosomal localization of the murine Testisin gene encoding a
      serine protease temporally expressed during spermatogenesis.
AB  - The recently characterized human serine protease, Testisin, is expressed on
      premeiotic testicular germ cells and is a candidate type II tumor suppressor for
      testicular cancer. Here we report the cloning, characterization and expression of
      the gene encoding mouse Testisin, Prss21. The murine Testisin gene comprises six
      exons and five introns and spans approximately 5 kb of genomic DNA with an almost
      identical structure to the human Testisin gene, PRSS21. The gene was localized to
      murine chromosome 17 A3.3-B; a region syntenic with the location of PRSS21 on
      human chromosome 16p13.3. Northern blot analyses of RNA from a range of adult
      murine tissues demonstrated a 1.3 kb mRNA transcript present only in testis. The
      murine Testisin cDNA shares 65% identity with human Testisin cDNA and encodes a
      putative pre-pro-protein of 324 amino acids with 80% similarity to human
      Testisin. The predicted amino-acid sequence includes an N-terminal signal
      sequence of 27 amino acids, a 27 amino-acid pro-region, a 251 amino-acid
      catalytic domain typical of a serine protease with trypsin-like specificity, and
      a C-terminal hydrophobic extension which is predicted to function as a membrane
      anchor. Immunostaining for murine Testisin in mouse testis demonstrated specific
      staining in the cytoplasm and on the plasma membrane of round and elongating
      spermatids. Examination of murine Testisin mRNA expression in developing sperm
      confirmed that the onset of murine Testisin mRNA expression occurred at
      approximately day 18 after birth, corresponding to the appearance of spermatids
      in the testis, in contrast to the expression of human Testisin in spermatocytes.
      These data identify the murine ortholog to human Testisin and demonstrate that
      the murine Testisin gene is temporally regulated during murine spermatogenesis.

PMID- 11231277
TI  - Expression and activity of ADAMTS-5 in synovium.
AB  - ADAMTS proteinases, belonging to the adamalysin subfamily of metalloproteinases,
      have been implicated in a variety of cellular events such as morphogenesis, cell
      migration, angiogenesis, ovulation and extracellular matrix breakdown.
      Aggrecanase-1 (ADAMTS-4) and aggrecanase-2 (ADAMTS-5) have been identified in
      cartilage and are largely responsible for cartilage aggrecan breakdown. We have
      shown previously that synovium, the membrane lining diarthrodial joints,
      generates soluble aggrecanase activity. We report here the expression,
      localization and activity of ADAMTS-5 from human arthritic and bovine synovium.
      ADAMTS-5 was expressed constitutively in synovium with little or no
      transcriptional regulation by recombinant human interleukin-1 alpha or all-trans
      retinoate, factors previously shown to upregulate aggrecanase activity in
      cartilage. Aggrecanase activity generated by synovium in vitro and recombinant
      ADAMTS-5 cleaved aggrecan extensively, resulting in aggrecan fragments similar to
      those generated by chondrocyte-derived aggrecanases, and the activity was
      inhibited by heparin. ADAMTS-5 was immunolocalized in human arthritic synovium,
      where staining was mostly pericellular, particularly in the synovial lining and
      around blood vessels; some matrix staining was also seen. The possibility that
      synovium-derived ADAMTS-5 may play a role in cartilage aggrecan breakdown is
      discussed.

PMID- 11231278
TI  - Sugar-based tertiary amino gemini surfactants with a vesicle-to-micelle
      transition in the endosomal pH range mediate efficient transfection in vitro.
AB  - Novel reduced sugar gemini amphiphiles linked through their tertiary amino head
      groups via alkyl spacers of 4 or 6 carbons, and with varying (unsaturated) alkyl
      tail lengths of 12--18, have been synthesized and tested for transfection in
      vitro in an adherent Chinese hamster ovary cell line (CHO-K1). Transfection
      efficiencies peaked at 2.7 times that of the commercial standard Lipofectamine
      Plus/2000 for pure solutions of the compound bearing unsaturated (oleyl) alkyl
      tails. For those compounds bearing saturated alkyl tails, transfection efficiency
      peaked at a tail length of 16, at a level similar to Lipofectamine Plus/2000. All
      of the amphiphiles formed bilayer vesicles at physiological pH. Some of the amino
      groups at the surface were protonated, and vesicles therefore bore a positive
      charge. Increased protonation with reduced pH resulted in greatly increased
      monomer solubility and a morphology change from vesicle to micelle at
      characteristic pH values, dependent on the tail length. For the compounds
      promoting high transfection efficiency, this characteristic pH was within the
      range found in the endosomal compartment (7.4--4.0). Formation of mixed micelles
      between gemini surfactant and membrane phospholipids at reduced pH may therefore
      provide a method of endosome rupture and subsequent escape of entrapped DNA, thus
      discarding the need for extra fusogenic or endosomolytic agents. The positive
      charge on the vesicles at physiological pH drives the colloidal association with
      DNA. Small angle X-ray scattering measurements indicate that lamellar aggregates
      are formed, which have a d spacing of 48--54 A. Preliminary differential scanning
      calorimetric measurements suggest that reduction of pH causes a disordering of
      the hydrocarbon region of the DNA-surfactant complex.

PMID- 11231279
TI  - Overexpression of the Golgi-localized enzyme alpha-mannosidase IIx in Chinese
      hamster ovary cells results in the conversion of hexamannosyl-N-acetylchitobiose
      to tetramannosyl-N-acetylchitobiose in the N-glycan-processing pathway.
AB  - Golgi alpha-mannosidase II is an enzyme that processes the intermediate
      oligosaccharide Gn(1)M(5)Gn(2) to Gn(1)M(3)Gn(2) during biosynthesis of N
      glycans. Previously, we isolated a cDNA encoding a protein homologous to alpha
      mannosidase II and designated it alpha-mannosidase IIx. Here, we show by
      immunocytochemistry that alpha-mannosidase IIx resides in the Golgi in HeLa
      cells. When coexpressed with alpha-mannosidase II, alpha-mannosidase IIx
      colocalizes with alpha-mannosidase II in COS cells. A protein A fusion of the
      catalytic domain of alpha-mannosidase IIx hydrolyzes a synthetic substrate, 4
      umbelliferyl-alpha-D-mannoside, and this activity is inhibited by swainsonine.
      [(3)H]glucosamine-labeled Chinese hamster ovary cells overexpressing alpha
      mannosidase IIx show a reduction of M(6)Gn(2) and an accumulation of M(4)Gn(2).
      Structural analysis identified M(4)Gn(2) to be Man alpha 1-->6(Man alpha 1-->2Man
      alpha 1-->3)Man beta 1-->4GlcNAc beta 1-->4GlcNAc. The results suggest that alpha
      mannosidase IIx hydrolyzes two peripheral Man alpha 1-->6 and Man alpha 1-->3
      residues from [(Man alpha 1-->6)(Man alpha 1-->3)Man alpha 1-->6](Man alpha 1-
      >2Man alpha 1-->3)Man beta 1-->4GlcNAc beta 1-->4GlcNAc, during N-glycan
      processing.

PMID- 11231280
TI  - Ectoenzymatic breakdown of diadenosine polyphosphates by Xenopus laevis oocytes.
AB  - Xenopus laevis oocytes exhibit ectoenzymatic activity able to hydrolytically
      cleave extracellular diadenosine polyphosphates (Ap(n)A). The basic properties of
      this ectoenzyme were investigated using as substrates di-(1,N(6)-ethenoadenosine)
      5',5"'-P(1),P(4)-tetraphospate [epsilon-(Ap(4)A)] and di-(1,N(6)-ethenoadenosine)
      5',5"'-P(1),P(5)-pentaphospate [epsilon-(Ap(5)A)], fluorogenic derivatives of
      Ap(4)A and Ap(5)A, respectively. epsilon-(Ap(4)A) and epsilon-(Ap(5)A) are
      hydrolysed by folliculated oocytes according to hyperbolic kinetics with K(m)
      values of 13.4 and 12.0 microM and Vmax values of 4.8 and 5.5 pmol per oocyte per
      min, respectively. The ectoenzyme is activated by Ca(2+) and Mg(2+), reaches
      maximal activity at pH 8--9 and is inhibited by suramin. Defolliculated oocytes
      also hydrolyse both substrates with similar K(m) values but V(max) values are
      approximately doubled with respect to folliculated controls. Chromatographic
      analysis indicates that extracellular epsilon-(Ap(4)A) and epsilon-(Ap(5)A) are
      first cleaved into 1,N(6)-ethenoAMP (epsilon-AMP) + 1,N(6)-ethenoATP (epsilon
      ATP) and epsilon-AMP + 1,N(6)-ethenoadenosine tetraphosphate (epsilon-Ap(4)),
      respectively, which are catabolized to 1,N(6)-ethenoadenosine (epsilon-Ado) as
      the end product by folliculated oocytes. Denuded oocytes, however, show a
      drastically reduced rate of epsilon-Ado production, epsilon-AMP being the main
      end-product of extracellular epsilon-(Ap(n)A) catabolism. Results indicate that,
      whereas the Ap(n)A-cleaving ectoenzyme appears to be located mainly in the
      oocyte, ectoenzymes involved in the dephosphorylation of mononucleotide moieties
      are located mainly in the follicular cell layer.

PMID- 11231281
TI  - Expression of penicillin G acylase from the cloned pac gene of Escherichia coli
      ATCC11105. Effects of pacR and temperature.
AB  - The structural gene pac in Eschericia coli ATCC11105 encodes penicillin G acylase
      (PGA). Within the pac gene, there is a regulatory gene pacR, which is transcribed
      in the opposite direction. Site-directed mutagenesis was performed at base 1045
      of pac by replacing a T with a C. This substitution did not alter the amino-acid
      sequence of PGA, but changed the translation start codon of pacR from AUG to GUG.
      The expression of the mutant pacR decreased dramatically and the lacZ
      transcriptional fusion analysis showed that GUG was an extremely poor initiation
      codon for pacR. The pacR mutation caused PGA expression to be constitutive rather
      than inductive in two strains (E. coli A56, DH10B). The pac inducer phenylacetic
      acid (PAA) gave significant induction of PGA production at a concentration of
      0.2% in wild type, but PAA at this concentration inhibited both cell growth and
      PGA production in the pacR mutated strains. The temperature-dependent expression
      character of pac is preserved in the pacR translation-initiation mutant and the
      optimum temperature of PGA production was 22 degrees C in both wild type and
      mutant. At a higher temperature of 37 degrees C, the PGA precursor polypeptide
      could not be matured into subunits and formed inclusion bodies, as revealed by
      western blot analysis. Our investigations confirmed the hypothesis of pacR
      mediated PAA induction for PGA expression and clarified the inhibitory effect of
      high temperature upon the post-translational processing of the PGA precursor
      polypeptide.

PMID- 11231282
TI  - Physico-chemical requirements for cellular uptake of pAntp peptide. Role of lipid
      binding affinity.
AB  - The pAntp peptide, corresponding to the third helix of the Antennapedia
      homeodomain, is internalized by a receptor-independent process into eucaryotic
      cells. The precise mechanism of entry remains unclear but the interaction between
      the phospholipids of plasma membrane and pAntp is probably involved in the
      translocation process. In order to define the role of peptide-lipid interaction
      in this mechanism and the physico-chemical properties that are necessary for an
      efficient cellular uptake, we have carried out an Ala-Scan mapping. The peptides
      were labeled with a fluorescent group (7-nitrobenz-2-oxo-1,3-diazol-4-yl-; NBD)
      and their cell association was measured by flow cytometry. Furthermore, we
      determined the fraction of internalized peptide by using a dithionite treatment.
      Comparison between cell association and cell uptake suggests that the affinity of
      pAntp for the plasma membrane is required for the import process. To further
      investigate which are the physico-chemical requirements for phospholipid-binding
      of pAntp, we have determined the surface partition coefficient of peptides by
      titrating them with phospholipid vesicles having different compositions. In
      addition, we estimated by circular dichroism the conformation adopted by these
      peptides in a membrane-mimetic environment. We show that the phospholipid binding
      of pAntp depends on its helical amphipathicity, especially when the negative
      surface charge density of phospholipid vesicles is low. The cell uptake of pAntp,
      related to lipid-binding affinity, requires a minimal hydrophobicity and net
      charge. As pAntp does not seem to translocate through an artificial phospholipid
      bilayer, this might indicate that it could interact with other cell surface
      components or enters into cells by a nonelucidated biological mechanism.

PMID- 11231283
TI  - Cloning and expression analysis of rainbow trout Oncorhynchus mykiss tumour
      necrosis factor-alpha.
AB  - A rainbow trout (Oncorhynchus mykiss) gene for tumor necrosis factor (TNF) has
      been cloned and sequenced. The cDNA contains an open reading frame of 738
      nucleotides that translate into a 246 amino-acid putative peptide, with a 5'
      untranslated region (UTR) of 140 bp and a 3' UTR of 506 bp. Two potential N
      linked glycosylation sites exist in the translation. The genomic sequence
      measures 2007 bp and contains three introns that intercept four coding exons.
      Expression studies using RT-PCR have shown that the trout TNF gene is
      constitutively expressed in the gill and kidney of unstimulated fish. Trout TNF
      expression could be up-regulated by stimulation of isolated head kidney
      leucocytes with lipopolysaccharide (LPS). Similarly, stimulation of a trout
      macrophage cell line (RTS11) with LPS resulted in an increased transcript level,
      as did incubation with recombinant trout interleukin (IL)-1 beta. The optimal
      timing for induction of TNF expression in trout macrophages was determined using
      recombinant trout IL-1 beta, where a clear induction was apparent by 2 h and
      peaked at 4 h. Evidence that this TNF gene is equivalent to mammalian TNF-alpha
      is discussed.

PMID- 11231284
TI  - Novel methylated triterpenoids of the gammacerane series from the nitrogen-fixing
      bacterium Bradyrhizobium japonicum USDA 110.
AB  - The nitrogen-fixing, symbiotic root-nodule forming bacterium Bradyrhizobium
      japonicum USDA 110 contained gammacerane derivatives next to triterpenoids of the
      hopane series. Diploptene, diplopterol, 2 beta-methyldiplopterol,
      aminobacteriohopanetriol and adenosylhopane were accompanied by tetrahymanol and
      the corresponding novel methylated homologues 2 beta-methyltetrahymanol, 20 alpha
      methyltetrahymanol, and 2 beta,20 alpha-dimethyltetrahymanol. Incorporation of
      [(2)H(3)]methyl-L-methionine indicated that the additional methyl groups
      originated from methionine, probably with S-adenosylmethionine acting as methyl
      donor, with retention of the three deuterium atoms. The simultaneous presence of
      hopane and gammacerane derivatives seems a characteristic feature of the genus
      Bradyrhizobium and the phylogenetically closely related Rhodopseudomonas
      palustris.

PMID- 11231285
TI  - Purification, characterization and cloning of isovaleryl-CoA dehydrogenase from
      higher plant mitochondria.
AB  - Between the different types of Acyl-CoA dehydrogenases (ACADs), those specific
      for branched chain acyl-CoA derivatives are involved in the catabolism of amino
      acids. In mammals, isovaleryl-CoA dehydrogenase (IVD), an enzyme of the leucine
      catabolic pathway, is a mitochondrial protein, as other acyl-CoA dehydrogenases
      involved in fatty acid beta-oxidation. In plants, fatty acid beta-oxidation takes
      place mainly in peroxisomes, and the cellular location of the enzymes involved in
      the catabolism of branched-chain amino acids had not been definitely assigned.
      Here, we describe that highly purified potato mitochondria have important IVD
      activity. The enzyme was partially purified and cDNAs from two different genes
      were obtained. The partially purified enzyme has enzymatic constant values with
      respect to isovaleryl-CoA comparable to those of the mammalian enzyme. It is not
      active towards straight-chain acyl-CoA substrates tested, but significant
      activity was also found with isobutyryl-CoA, implying an additional role of the
      enzyme in the catabolism of valine. The present study confirms recent reports
      that in plants IVD activity resides in mitochondria and opens the way to a more
      detailed study of amino-acid catabolism in plant development.

PMID- 11231286
TI  - Identification and characterization of SEB, a novel protein that binds to the
      acute undifferentiated leukemia-associated protein SET.
AB  - SET, the translocation breakpoint-encoded protein in acute undifferentiated
      leukemia (AUL), is a 39-kDa nuclear phosphoprotein and has an inhibitory activity
      for protein phosphatase 2A (PP2A). SET is fused to a putative oncoprotein,
      CAN/NUP214, in AUL and is thought to play a key role in leukemogenesis by its
      nuclear localization, protein-protein interactions and PP2A inhibitory activity.
      Here, we describe the isolation and characterization of a novel cDNA encoding a
      protein with 1542 amino-acid residues that specifically interacts in a yeast two
      hybrid system as well as in human cells with SET. This new protein, which we name
      SEB (SET-binding protein), is identified as a 170-kDa protein by
      immunoprecipitation with a specific antibody and is localized predominantly in
      the nucleus. SEB1238--1434 is determined as a SET-binding region that
      specifically binds to SET182--223. SEB also has an oncoprotein Ski homologous
      region (amino acids 654--858), six PEST sequences and three sequential PPLPPPPP
      repeats at the C-terminus. SEB mRNA is expressed ubiquitously in all human adult
      tissues and cells examined. The SEB gene locus is assigned to the chromosome
      18q21.1 that contains candidate tumor suppressor genes associated with deletions
      in cancer and leukemia. Although the function of SEB is not known, we propose
      that SEB plays a key role in the mechanism of SET-related leukemogenesis and
      tumorigenesis, perhaps by suppressing SET function or by regulating the
      transforming activity of Ski in the nucleus.

PMID- 11231287
TI  - Resistance to induced apoptosis in the human neuroblastoma cell line SK-N-SH in
      relation to neuronal differentiation. Role of Bcl-2 protein family.
AB  - Much evidence suggests that apoptosis plays a crucial role in cell population
      homeostasis that depends on the expression of various genes implicated in the
      control of cell life and death. The sensitivity of human neuroblastoma cells SK-N
      SH to undergo apoptosis induced by thapsigargin was examined. SK-N-SH were
      previously differentiated into neuronal cells by treatments with retinoic acid
      (RA), 4 beta-phorbol 12-myristate 13-acetate (PMA) which increases protein kinase
      C (PKC) activity, and staurosporine which decreases PKC activity. Neuronal
      differentiation was evaluated by gamma-enolase, microtubule associated protein 2
      (MAP2) and synaptophysin immunocytochemistry. The sensitivity of the cells to
      thapsigargin-induced apoptosis was evaluated by cell viability and nuclear
      fragmentation (Hoechst 33258) and compared with pro-(Bcl-2, Bcl-x(L)) and anti
      apoptotic (Bax, Bak) protein expression of the Bcl-2 family. Cells treated with
      RA and PMA were more resistant to apoptosis than controls. Conversely, the cells
      treated with staurosporine were more susceptible to apoptosis. In parallel with
      morphological modifications, the expression of inhibitors and activators of
      apoptosis was directly dependent upon the differentiating agent used. Bcl-2
      expression was strongly increased by PMA and drastically decreased by
      staurosporine as was Bcl-x(L) expression. Bax and Bak expression were not
      significantly modified. These results demonstrate that drugs that modulate PKC
      activity may induce a modification of Bcl-2 expression as well as resistance to
      the apoptotic process. Furthermore, the expression of Bcl-2 was reduced by toxin
      B from Clostridium difficile and, to a lesser extent, by wortmannin suggesting a
      role of small G-protein RhoA and PtdIns3 kinase in the control of Bcl-2
      expression. Our data demonstrate a relationship between the continuous activation
      of PKC, the expression of Bcl-2 protein family and the resistance of
      differentiated SK-N-SH to apoptosis.

PMID- 11231288
TI  - p-Hydroxyphenylacetate decarboxylase from Clostridium difficile. A novel glycyl
      radical enzyme catalysing the formation of p-cresol.
AB  - The human pathogenic bacterium Clostridium difficile is a versatile organism
      concerning its ability to ferment amino acids. The formation of p-cresol as the
      main fermentation product of tyrosine by C. difficile is unique among clostridial
      species. The enzyme responsible for p-cresol formation is p-hydroxyphenylacetate
      decarboxylase. The enzyme was purified from C. difficile strain DMSZ 1296(T) and
      initially characterized. The N-terminal amino-acid sequence was 100% identical to
      an open reading frame in the unfinished genome of C. difficile strain 630. The
      ORF encoded a protein of the same size as the purified decarboxylase and was very
      similar to pyruvate formate-lyase-like proteins from Escherichia coli and
      Archaeoglobus fulgidus. The enzyme decarboxylated p-hydroxyphenylacetate (K(m) =
      2.8 mM) and 3,4-dihydroxyphenylacetate (K(m) = 0.5 mM). It was competitively
      inhibited by the substrate analogues p-hydroxyphenylacetylamide and p
      hydroxymandelate with K(i) values of 0.7 mM and 0.48 mM, respectively. The
      protein was readily and irreversibly inactivated by molecular oxygen. Although
      the purified enzyme was active in the presence of sodium sulfide, there are some
      indications for an as yet unidentified low molecular mass cofactor that is
      required for catalytic activity in vivo. Based on the identification of p
      hydroxyphenylacetate decarboxylase as a novel glycyl radical enzyme and the
      substrate specificity of the enzyme, a catalytic mechanism involving ketyl
      radicals as intermediates is proposed.

PMID- 11231289
TI  - Multiple signaling cascades are differentially involved in gene induction by
      double stranded RNA in interferon-alpha-primed cells.
AB  - Priming with interfon (IFN)alpha enhanced the ability of the synthetic double
      stranded RNA polyriboinosinic acid: polyribocytidilic acid (pI:C), but not
      interleukin-1 beta, to activate both p38 mitogen-activated kinase (MAPK) and
      extracellular signal-regulated kinase (ERK) signaling cascades. Activation by
      pI:C in IFN alpha-primed cells was delayed compared to activation with
      interleukin-1 beta, and this delay was followed by high, sustained activation of
      p38 MAPK and a modest elevation of ERK activation. Pharmacologic inhibition of
      either the ERK or the p38 MAPK pathway, using U0126 and SB203580, respectively,
      reduced interleukin-6 protein induction by at least 70%, and combined inhibition
      of both pathways fully blocked interleukin-6 protein expression and reduced
      interleukin-6 mRNA induction by more than 80%. In contrast, induction of double
      stranded RNA-activated protein kinase (PKR) mRNA and protein by IFN alpha and/or
      pI:C was minimally affected by either inhibitor. Induction of interferon
      regulatory factor-1 (IRF-1) by pI:C in IFN alpha primed cells was profoundly
      inhibited by U0126 but not by SB203580. Thus, IFN alpha priming enhances
      activation of p38 MAPK and ERK pathways by pI:C but not by interleukin-1 beta,
      thereby enhancing the expression of some, but not all, genes that are induced by
      pI:C.

PMID- 11231290
TI  - Structure-activity relationship of the p55 TNF receptor death domain and its
      lymphoproliferation mutants.
AB  - Upon stimulation with tumor necrosis factor (TNF), the TNF receptor (TNFR55)
      mediates a multitude of effects both in normal and in tumor cells. Clustering of
      the intracellular domain of the receptor, the so-called death domain (DD), is
      responsible for both the initiation of cell killing and the activation of gene
      expression. To characterize this domain further, TNFR55 DD was expressed and
      purified as a thioredoxin fusion protein in Escherichia coli. Circular dichroism,
      steady-state and time-resolved fluorescence spectroscopy were used to compare
      TNFR55 DD with DDs of the Fas antigen (Fas), the Fas-associating protein with DD
      (FADD) and p75 nerve growth factor receptor, for which the 3-dimensional
      structure are already known. The structural information derived from the
      measurements strongly suggests that TNFR55 DD adopts a similar fold in solution.
      This prompted a homology modeling of the TNFR DD 3-D structure using FADD as a
      template. In vivo studies revealed a difference between the two
      lymphoproliferation (lpr) mutations. Biophysical techniques were used to analyze
      the effect of changing Leu351 to Ala and Leu351 to Asn on the global structure
      and its impact on the overall stability of TNFR55 DD. The results obtained from
      these experiments in combination with the modeled structure offer an explanation
      for the in vivo observed difference.

PMID- 11231291
TI  - Effects of methylcyclodextrin on lysosomes.
AB  - The cholesterol complexing agent methyl-cyclodextrin (MCD) provides an efficient
      mean for the removal of cholesterol from biological membranes. In order to study
      the effects of this agent on the lysosomal membrane in situ, we treated HepG2
      cells with MCD and studied the effects of this treatment on lysosomes in isolated
      fractions. We found that lysosomes prepared from treated cells are more sensitive
      to various membrane perturbing treatments such as: incubation of lysosomes in
      isotonic glucose, in hypotonic sucrose or in the presence of the lytic agent
      glycyl-L-phenylalanine 2-naphthylamide. The lysosomal membrane is also less
      resistant to increased hydrostatic pressure. Centrifugation methods were used to
      analyse the effect of MCD on lysosomes. Isopycnic centrifugation in sucrose
      density gradients demonstrates that the drug induces a reversible density
      increase of the lysosomes. Our study indicates that extracellularly added MCD can
      modify the properties of the lysosomal membrane in living cells. It suggests that
      MCD could be an effective tool to modulate the physical properties of lysosomes
      within intact cells and to monitor the cellular responses to such modifications.

PMID- 11231292
TI  - Disulfide bond assignment, lipid transfer activity and secondary structure of a 7
      kDa plant lipid transfer protein, LTP2.
AB  - The 7-kDa lipid transfer proteins, LTP2s, share some amino-acid sequence
      similarities with the 9-kDa isoforms, LTP1s. Both proteins display an identical
      cysteine motif and, in this regard, LTP2s have been classified as lipid transfer
      proteins. However, in contrast with LTP1s, no data are available on their
      structure, cysteine pairings, lipid transfer and lipid binding properties. We
      reported on the isolation of two isoforms of 7-kDa lipid transfer protein, LTP2,
      from wheat seeds and showed for the first time that they indeed display lipid
      transfer activity. Trypsin and chymotrypsin digestions of the native LTP2
      afforded the sequence of both isoforms and assignment of disulfide bonds. The
      cysteine pairings, Cys10--Cys24, Cys25--Cys60, Cys2--Cys34, Cys36--Cys67,
      revealed a mismatch at the Cys34-X-Cys36 motif of LTP2 compared to LTP1.
      Moreover, the secondary structure as determined by circular dichroism suggested
      an identical proportion of alpha helices, beta sheets and random coils. By
      analogy with the structure of the LTP1, we discussed what structural changes are
      required to accommodate the LTP2 disulfide pattern.

PMID- 11231293
TI  - Thioredoxin peroxidases of the malarial parasite Plasmodium falciparum.
AB  - The open reading frames of two different proteins with homologies to 2-Cys
      peroxiredoxins have been identified in the P. falciparum genome. Both genes, with
      a length of 585 and 648 bp, respectively, were amplified from a gametocyte cDNA
      and overexpressed in Escherichia coli. The gene products (deduced m 21.8 and 24.6
      kDa) with an overall identity of 51.8% were found to be active in the glutamine
      synthetase protector assay. The smaller protein (named Pf-thioredoxin peroxidase
      1; PfTPx1) is reduced by P. falciparum thioredoxin (PfTrx) and accepts H(2)O(2),
      t-butylhydroperoxide, and cumene hydroperoxide as substrates, the respective
      k(cat) values for the N-terminally His-tagged protein in the presence of 10
      microM PfTrx and 200 microM substrate being 67, 56, and 41 min(-1) at 25 degrees
      C. As described for many peroxiredoxins, PfTPx1 does not follow saturation
      kinetics. Furthermore, in oxidizing milieu both proteins are converted to another
      protein species migrating faster in SDS gel electrophoresis. For PfTPx1 also this
      second species was found to be active, however, with different kinetic properties
      which might indicate a mechanism of enzyme regulation in vivo.

PMID- 11231295
TI  - Different sensitivity of rabbit heart and skeletal muscle to endotoxin-induced
      impairment of mitochondrial function.
AB  - The involvement of mitochondrial dysfunction in septic disturbances of tissues is
      controversial. The aim of this study was to investigate the effects of endotoxin
      induced sepsis on the function of heart and skeletal muscle mitochondria. Rabbits
      were made septic by subcutaneous injection of endotoxin (lipopolysaccharide, LPS)
      from Escherichia coli at concentrations of 100 or 150 microg LPS.kg(-1) 24 h
      prior to the experiments. Mitochondrial respiration was measured in saponin
      skinned muscle fibers and compared with photometrically detected activities of
      respiratory chain enzymes as well as with function of perfused hearts. In heart
      fibers a dosage of 100 microg LPS.kg(-1) caused a significant decrease of state 3
      respiration for the substrates pyruvate (-38%), octanoyl-carnitine (-38%) and
      succinate (-30%) with correspondingly decreased respiratory control indexes
      (RCI). In addition, endotoxin caused a decreased temporal stability of the rate
      of state 3-respiration. At least in part these changes can be attributed to a
      reduced activity of complex I + III (-50%) of the respiratory chain. State 4
      respiration rates were not significantly altered. The lowered state 3-respiration
      in heart mitochondria seems to contribute to the impairment of heart muscle
      function as detected by an increase of coronary vascular resistance (CVR) in
      endotoxin-treated hearts. Functional properties of mitochondria from M. Vastus
      lasteralis were not affected by 100 microg LPS.kg(-1) but a higher dosage of 150
      microg LPS.kg(-1) caused decreased RCI for the substrates pyruvate (-29%) and
      octanoyl-carnitine (-32%). Also the activity of complex I + III was not
      significantly affected at lower dose of endotoxin but decreased (-42%) after
      treatment with 150 microg LPS.kg(-1). Results demonstrate the involvement of
      impaired mitochondria in the pathophysiology of septic organ failure and a tissue
      specificity of endotoxaemia.

PMID- 11231294
TI  - Protein-glutaminase from Chryseobacterium proteolyticum, an enzyme that
      deamidates glutaminyl residues in proteins. Purification, characterization and
      gene cloning.
AB  - A novel protein-deamidating enzyme was purified to homogeneity from
      Chryseobacterium proteolyticum and the gene encoding it was cloned. The enzyme is
      a monomer with a pI of 10.0, a measured M(r) of approximately 20,000 and a
      calculated M(r) of 19,860. Extensive comparison with Streptoverticillium
      transglutaminase showed that the protein-deamidating enzyme lacked
      transglutaminase activity in terms of hydroxamate-formation between
      benzyloxycarbonyl-Gln-Gly and hydroxylamine, or monodansylcadaverine
      incorporation into casein. The enzyme deamidated the two glutaminyl residues in
      the oxidized insulin A chain and deamidated both casein and the oxidized insulin
      B chain with higher catalytic efficiencies (k(cat)/K(m)) than with short
      peptides. The enzyme was active against several proteins, including insoluble
      wheat gluten, but did not deamidate asparaginyl residues in peptides, free
      glutamine or other amides. The enzyme was therefore named protein-glutaminase (EC
      3.5.1). The gene encoding the protein was cloned and, when expressed in
      Escherichia coli, the protein product had protein-glutaminase activity and cross
      reacted with antiserum raised against the purified enzyme. The protein
      glutaminase was shown to be expressed as a prepro-protein with a putative signal
      peptide of 21 amino acids and a pro-sequence of 114 amino acids. The amino-acid
      sequence had no obvious homology to any published sequence and is therefore a
      novel protein-glutaminase.

PMID- 11231296
TI  - A change in ionization of the NADP(H)-binding component (dIII) of proton
      translocating transhydrogenase regulates both hydride transfer and nucleotide
      release.
AB  - Transhydrogenase couples the transfer of hydride-ion equivalents between NAD(H)
      and NADP(H) to proton translocation across a membrane. The enzyme has three
      components: dI binds NAD(H), dIII binds NADP(H) and dII spans the membrane.
      Coupling between transhydrogenation and proton translocation involves changes in
      the binding of NADP(H). Mixtures of isolated dI and dIII from Rhodospirillum
      rubrum transhydrogenase catalyse a rapid, single-turnover burst of hydride
      transfer between bound nucleotides; subsequent turnover is limited by NADP(H)
      release. Stopped-flow experiments showed that the rate of the hydride transfer
      step is decreased at low pH. Single Trp residues were introduced into dIII by
      site-directed mutagenesis. Two mutants with similar catalytic properties to those
      of the wild-type protein were selected for a study of nucleotide release. The way
      in which Trp fluorescence was affected by nucleotide occupancy of dIII was
      different in the two mutants, and hence two different procedures for determining
      the rate of nucleotide release were developed. The apparent first-order rate
      constants for NADP(+) release and NADPH release from isolated dIII increased
      dramatically at low pH. It is concluded that a single ionisable group in dIII
      controls both the rate of hydride transfer and the rate of nucleotide release.
      The properties of the protonated and unprotonated forms of dIII are consistent
      with those expected of intermediates in the NADP(H)-binding-change mechanism. The
      ionisable group might be a component of the proton-translocation pathway in the
      complete enzyme.

PMID- 11231297
TI  - Regulation of the activity of matriptase on epithelial cell surfaces by a blood
      derived factor.
AB  - Matriptase is an epithelial-derived, integral membrane, trypsin-like serine
      protease. We have shown previously that matriptase exists both in complexed and
      noncomplexed forms. We now show that the complexed matriptase is an activated,
      two-chain form, which is inhibited in an acid-sensitive, reversible manner
      through binding to its cognate, Kunitz-type inhibitor, HAI-1 (hepatocyte growth
      factor activator inhibitor-1). Conversely, the majority of the noncomplexed
      matriptase is a single-chain zymogen, which lacks binding affinity to HAI-1,
      suggesting that matriptase, similar to most other serine proteases, is activated
      by proteolytic cleavage at a canonical activation motif. We have now generated
      mAbs specific for the conformational changes associated with the proteolytic
      activation of matriptase. Using these mAbs, which specifically recognize the two
      chain form of matriptase, we demonstrate that matriptase is transiently activated
      on 184A1N4 human mammary epithelial cell surfaces following their exposure to
      serum. The ability of serum to activate matriptase is highly conserved across
      reptilian, avian, and mammalian species. This serum-dependent activation of
      matriptase on epithelial cell surfaces is followed by ectodomain shedding of both
      matriptase and its Kunitz-type inhibitor.

PMID- 11231298
TI  - Expression and induction of a large set of drug-metabolizing enzymes by the
      highly differentiated human hepatoma cell line BC2.
AB  - The BC2 cell line derived from the human hepatocarcinoma, HGB, undergoes a
      spontaneous sharp differentiation process in culture as it becomes confluent,
      remains stably differentiated for several weeks, and may return to proliferation
      thereafter under appropriate density conditions. The relevance of the line as an
      hepatic model has been evaluated. Cells synthesize a large number of plasma
      proteins, and rates of glycogen and urea synthesis increase with time of
      confluency and become sensitive to insulin, reflecting the process of
      differentiation. Differentiated BC2 cells express the most relevant cytochrome P
      450 (CYP) isozyme activities (CYP1A1/2, 2A6, 2B6, 2C9, 2E1, and 3A4) and
      conjugating enzymes (glutathione S-transferase and UDP-glucuronyltransferase) and
      also respond to model inducers. Methylcholanthrene induced an increase in
      CYP1A1/2 enzyme activity (eightfold), phenobarbital induced CYP2B6 activity (1.7
      fold), and dexamethasone induced CYP3A4 activity (fivefold). In parallel,
      expression of the most relevant liver-enriched transcription factors, HNF-4, HNF
      1, C/EBP-alpha and C/EBP-beta mRNAs, was significantly increased in
      differentiated cultures. This increase was largest in HNF-1 and HNF-4, which
      supports the idea that a redifferentiation process towards the hepatic phenotype
      takes place. BC2 is an hepatic cell line that is able to express most hepatic
      functions, especially the drug-biotransformation function, far more efficiently
      than any previously described human hepatoma cell line.

PMID- 11231299
TI  - Oxidation of polychlorinated benzenes by genetically engineered CYP101
      (cytochrome P450(cam)).
AB  - Polychlorinated benzenes are recalcitrant environmental pollutants primarily
      because they are resistant to attack by dioxygenases commonly used by micro
      organisms for the biodegradation of aromatic compounds. We have investigated the
      oxidation of polychlorinated benzenes by mutants of the haem mono-oxygenase
      CYP101 (cytochrome P450(cam)) from Pseudomonas putida with the aim of generating
      novel systems for their biodegradation. Wild-type CYP101 had low activity for the
      oxidation of dichlorobenzenes and trichlorobenzenes to the chlorophenols, but no
      products were detected for the heavily chlorinated benzenes. Increasing the
      active-site hydrophobicity with the Y96F mutation increased the activity up to
      100-fold, and both pentachlorobenzene and hexachlorobenzene were oxidized slowly
      to pentachlorophenol. Decreasing the space available at the top of the active
      site with the F87W mutation to force the substrate to be bound closer to the haem
      resulted in a further 10-fold increase in activity with most substrates.
      Introducing the F98W mutation, also at the top of the active site, decreased the
      NADH-turnover rates but increased the coupling efficiencies, and > 90% coupling
      was observed for 1,3-dichlorobenzene and 1,3,5-trichlorobenzene with the F87W-
      Y96F--F98W mutant. The V247L mutation generally increased the NADH-turnover
      rates, and the F87W--Y96F--V247L mutant showed reasonably fast NADH turnover (229
      min(-1)) with the highly insoluble pentachlorobenzene without the need for
      surfactants or organic cosolvents. As all chlorophenols are degraded by micro
      organisms, novel biodegradation systems could be constructed in which CYP101
      mutants convert the inert polychlorinated benzenes to the phenols, which are then
      readily degraded by natural pathways.

PMID- 11231300
TI  - Structure and promoter analysis of the mouse membrane-bound transferrin-like
      protein (MTf) gene.
AB  - Recently, we purified membrane-bound transferrin-like protein (MTf) from the
      plasma membrane of rabbit chondrocytes and showed that the expression levels of
      MTf protein and mRNA were much higher in cartilage than in other tissues
      [Kawamoto T, Pan, H., Yan, W., Ishida, H., Usui, E., Oda, R., Nakamasu, K.,
      Noshiro, M., Kawashima-Ohya, Y., Fujii, M., Shintani, H., Okada, Y. & Kato, Y.
      (1998) Eur. J. Biochem. 256, 503--509]. In this study, we isolated the MTf gene
      from a constructed mouse genomic library. The mouse MTf gene was encoded by a
      single-copy gene spanning approximately 26 kb and consisting of 16 exons. The
      transcription-initiation site was located 157 bp upstream from the translation
      start codon, and a TATA box was not found in the 5' flanking region. The mouse
      MTf gene was mapped on the B3 band of chromosome 16 by fluorescence in situ
      hybridization. Using primary chondrocytes, SK-MEL-28 (melanoma cell line), ATDC5
      (chondrogenic cell line) and NIH3T3 (fibroblast cell line) cells, we carried out
      transient expression studies on various lengths of the 5' flanking region of the
      MTf gene fused to the luciferase reporter gene. Luciferase activity in SK-MEL-28
      cells was higher than in primary chondrocytes. Although no luciferase activity
      was detectable in NIH3T3 cells, it was higher in chondrocytes than in ATDC5
      chondrogenic cells. These findings were consistent with the levels of expression
      of MTf mRNA in these cells cultured under similar conditions. The patterns of
      increase and decrease in the luciferase activity in chondrocytes transfected with
      various 5' deleted constructs of the MTf promoter were similar to that in ATDC5
      cells, but differed from that in SK-MEL-28 cells. The findings obtained with
      primary chondrocytes suggest that the regions between -693 and -444 and between 
      1635 and -1213 contain positive and negative cis-acting elements, respectively.
      The chondrocyte-specific expression of the MTf gene could be regulated via these
      regulatory elements in the promoter region.

PMID- 11231301
TI  - Heat capacity analysis of oxidized Escherichia coli thioredoxin fragments (1--73,
      74--108) and their noncovalent complex. Evidence for the burial of apolar surface
      in protein unfolded states.
AB  - We have calculated the absolute heat capacities of fragments 1--73 (N fragment)
      and 74--108 (C fragment) from thioredoxin, their complex and the uncleaved
      protein, from the concentration dependence of the apparent heat capacities of the
      solutions determined by differential scanning calorimetry. We find that, while
      the absolute heat capacities of uncleaved, unfolded thioredoxin and the C
      fragment are in good agreement with the theoretical values expected for fully
      solvated chains (calculated as the sum of the contributions of the constituent
      amino acids), the absolute heat capacities of the N fragment and the unfolded
      complex are about 2 kJ x K(-1) x mol(-1) lower than the fully solvated-chain
      values. We attribute this discrepancy to burial of the apolar surface in the N
      fragment (as burial of the polar area is expected to lead to an increase in heat
      capacity). Illustrative calculations suggest that burial of about 1000--1600 A(2)
      of apolar surface takes place in the N fragment (probably accompanied by the
      burial of a smaller amount of polar surface). In general, this work is supportive
      of heat capacity measurements on protein fragments being useful as probes of
      surface burial in studies to characterize protein unfolded states and the high
      regions of protein folding landscapes.

PMID- 11231302
TI  - Reduction of ubiquinone by lipoamide dehydrogenase. An antioxidant regenerating
      pathway.
AB  - Lipoamide dehydrogenase belongs to a family of pyridine nucleotide disulfide
      oxidoreductases and is ubiquitous in aerobic organisms. This enzyme also reduces
      ubiquinone (the only endogenously synthesized lipid-soluble antioxidant) to
      ubiquinol, the form in which it functions as an antioxidant. The reduction of
      ubiquinone was linear with time and exhibited turnover numbers of 5 and 1.2 min(
      1) in the presence and absence of zinc, respectively. The reaction was stimulated
      by zinc and cadmium but not by the other divalent ions tested. The zinc/cadmium
      dependent stimulation of the reaction increased rapidly and linearly up to a
      concentration of 0.1 mM and was even further increased at 0.5 mM. At pH 6, the
      activity was three times higher than at physiological pH. Alteration of the NADPH
      : NADP(+) ratio revealed that the reaction is inhibited by higher concentrations
      of the oxidized cofactors. FAD reduced ubiquinone in a dose-dependent manner at a
      considerably lower rate, suggesting that the reduction of ubiquinone by lipoamide
      dehydrogenase involves the FAD moiety of the enzyme.

PMID- 11231303
TI  - High levels of ceruloplasmin in the serum of transgenic mice developing
      hepatocellular carcinoma.
AB  - Transgenic mice expressing the Simian virus 40 large T antigen under the control
      of the liver-specific human antithrombin-III promoter all develop well
      differentiated hepatocellular carcinoma. During tumour development serum
      ceruloplasmin (Cp) increases gradually until it reaches 30 times control levels
      in all transgenic mice at 6 months of age. The accumulation of Cp in the serum is
      due to the increased transcription of the Cp gene as well as to the increase in
      Cp mRNA stability in the livers of the transgenic mice. One-half of the
      overproduced Cp is charged with copper and Cp-associated serum oxidase activity
      increases in parallel with the holo-Cp concentration. Through its ferroxidase
      activity Cp is involved prominently in iron metabolism. Analysis of copper and
      iron in serum and liver revealed increased copper levels in the serum of tumour
      bearing animals and which increased in parallel with Cp concentration; the
      amounts of copper in the liver were unchanged. In contrast, serum iron remained
      constant during tumour development whereas the iron concentration in the livers
      of the transgenic mice decreased.

PMID- 11231304
TI  - Molecular cloning and biochemical characterization of a lipoxygenase in almond
      (Prunus dulcis) seed.
AB  - We have characterized an almond (Prunus dulcis) lipoxygenase (LOX) that is
      expressed early in seed development. The presence of an active lipoxygenase was
      confirmed by western blot analysis and by measuring the enzymatic activity in
      microsomal and soluble protein samples purified from almond seeds at this stage
      of development. The almond lipoxygenase, which had a pH optimum around 6, was
      identified as a 9-LOX on the basis of the isomers of linoleic acid hydroperoxides
      produced in the enzymatic reaction. A genomic clone containing a complete
      lipoxygenase gene was isolated from an almond DNA library. The 6776-bp sequence
      reported includes an open reading frame of 4667 bp encoding a putative
      polypeptide of 862 amino acids with a calculated molecular mass of 98.0 kDa and a
      predicted pI of 5.61. Almond seed lipoxygenase shows 71% identity with an
      Arabidopsis LOX1 gene and is closely related to tomato fruit and potato tuber
      lipoxygenases. The sequence of the active site was consistent with the isolated
      gene encoding a 9-LOX.

PMID- 11231305
TI  - Tyrosine phosphorylation-dependent activation of NF-kappa B. Requirement for p56
      LCK and ZAP-70 protein tyrosine kinases.
AB  - Phosphorylation of the N-terminal domain of I kappa B inhibitory subunits induces
      activation of the transcription factor NF-kappa B. Although serine
      phosphorylation has been shown to induce ubiquitination and subsequent proteasome
      mediated degradation of I kappa B-alpha, little is known about the mechanisms
      that lead to release of active NF-kappa B in T cells as a consequence of tyrosine
      phosphorylation of I kappa B-alpha [Imbert, V., Rupec, R.A., Livolsi, A., Pahl,
      H.L., Traenckner, B.M., Mueller-Dieckmann, C., Farahifar, D., Rossi, B.,
      Auberger, P., Baeuerle, P. & Peyron, J.F. (1996) Cell 86, 787--798]. The
      involvement of the tyrosine kinases p56(lck) and ZAP-70 in this reaction is
      demonstrated here using specific pharmacological inhibitors and Jurkat mutants
      unable to express these kinases. Although the inhibitors prevented both
      pervanadate-induced phosphorylation of I kappa B-alpha on Tyr42 and NF-kappa B
      activation, we observed that, in p56(lck)-deficient Jurkat mutants, NF-kappa B
      could still associate with I kappa B-alpha despite phosphorylation on Tyr42.
      Furthermore, the SH2 domain of p56(lck) appeared to be required for pervanadate
      induced NF-kappa B activation but not for Tyr42 phosphorylation. These results
      show that p56(lck) and ZAP-70 are key components of the signaling pathway that
      leads to phosphotyrosine-dependent NF-kappa B activation in T cells and confirm
      that tyrosine kinases must control at least two different steps to induce
      activation of NF-kappa B. Finally, we show that H(2)O(2), which stimulates
      p56(lck) and ZAP-70 in T cells, is an activator of NF-kappa B through tyrosine
      phosphorylation of I kappa B-alpha.

PMID- 11231307
TI  - Cancer cell expression of urokinase-type plasminogen activator receptor mRNA in
      squamous cell carcinomas of the skin.
AB  - In this study we have used in situ hybridization with radiolabeled antisense RNA
      probes to examine the expression of mRNA for urokinase-type plasminogen activator
      and its receptor in histologic samples of squamous cell (n = 7) and basal cell (n
      = 7) carcinomas of the skin. Messenger RNA for both urokinase-type plasminogen
      activator and its receptor were expressed in all of the squamous cell carcinomas,
      but could not be detected in the basal cell carcinomas. In all of the seven
      squamous cell carcinomas a signal for urokinase-type plasminogen activator
      receptor mRNA was detected focally in well-differentiated cancer cells
      surrounding keratinized pearls, and in four specimens urokinase-type plasminogen
      activator receptor mRNA was in addition expressed by cancer cells at the edge of
      invasively growing strands of tumor. Urokinase-type plasminogen activator mRNA
      expression was found in virtually all the cancer cells of the squamous cell
      carcinomas, and importantly we found, by hybridizations for urokinase-type
      plasminogen activator and its receptor mRNA on adjacent sections of squamous cell
      carcinomas, that it was exactly the invading cancer cells that simultaneously
      expressed both these components required for plasmin-mediated proteolysis at the
      cell surface. We have previously shown that both urokinase-type plasminogen
      activator and its receptor mRNA are expressed by the leading-edge keratinocytes
      in regenerating epidermis during mouse skin wound healing, and that wound healing
      is impaired in mice made deficient in plasminogen by targeted gene disruption. We
      propose that there are similarities between the mechanisms of generation and
      regulation of extracellular proteolysis during skin re-epithelialization and
      squamous cell carcinoma invasion. The ability of the squamous carcinoma cells to
      mimic the "invasive" phenotype of re-epithelializing keratinocytes may be one of
      the factors that make squamous cell carcinomas more aggressive tumors than basal
      cell carcinomas.

PMID- 11231308
TI  - A novel type II cytokeratin, mK6irs, is expressed in the Huxley and Henle layers
      of the mouse inner root sheath.
AB  - Hair follicle differentiation involves the expression of both epithelial-type
      keratins or cytokeratins and hair keratins as well as hair keratin-associated
      proteins. In this study, a cDNA clone encoding a cytokeratin family member was
      isolated using RNA differential display techniques. The predicted amino acid
      sequence derived from this clone, revealed a homology with a number of
      cytokeratins, not only in the central alpha-helical regions but also in the
      conserved portions of the amino and carboxy terminal domains, indicating that
      this protein represents a new member of the mouse type II cytokeratin family.
      Northern blot analysis showed expression in mouse skin, but not in other tissues,
      including tongue, esophagus, and forestomach. One- and two-dimensional western
      blot analysis showed that this new cytokeratin was 57 kDa in size and ran
      slightly below the area of cytokeratin 5, which corresponded to that of the
      cytokeratin 6 family members. Both RNA in situ hybridization and
      immunohistochemical studies of mouse anagen hair follicles demonstrated
      expression of this cytokeratin in the inner root sheath hair cone during anagen
      III and in the Henle and Huxley layers of the inner root sheath during anagen VI.
      The expression of the new cytokeratin began in the hair bulb and progressed up to
      the height of the keratogenous zone. Taken together the sum of the data analyzed,
      we have termed this novel cytokeratin mK6irs (mouse gene nomenclature k2-6g) to
      indicate both its similar mobility with K6 in two-dimensional gels and its
      specific expression in the inner root sheath of the hair follicle.

PMID- 11231309
TI  - Impact of Bcl-2 and Ha-ras on keratinocytes in organotypic culture.
AB  - In this study, the role of specific molecular alterations associated with
      multistep skin carcinogenesis was assessed using in vitro organotypic cultures of
      the spontaneously immortalized, nontumorigenic HaCaT keratinocyte cell line.
      HaCaT vector control clones and clones expressing bcl-2, activated Ha-ras, or
      both genes were generated. Clones were induced to stratify and differentiate by
      culturing on dermal equivalents for 2 wk at the air-medium interface. In parental
      and vector control HaCaT rafts the expression and distribution of cytokeratin K1,
      K14, involucrin, proliferating cell nuclear antigen, and p21cip1/waf1 were
      assessed using immunohistochemistry and immunoblotting and were similar to normal
      epidermis. Apoptosis was also examined using the TUNEL technique. HaCaT-bcl-2
      rafts were similar to control rafts but exhibited lower spontaneous rates of
      apoptosis and a moderate increase in the rate of proliferation. Differentiation
      was significantly inhibited in HaCaT-ras organotypic cultures and was associated
      with high rates of proliferation and lower rates of spontaneous apoptosis.
      Additionally, HaCaT-ras rafts exhibited significantly higher rates of apoptosis
      following ultraviolet irradiation compared with vector control or HaCaT-bcl-2
      rafts. Bcl-2 was able to largely restore normal differentiation, proliferation,
      and apoptosis in HaCaT-ras/bcl-2 organotypic cultures. Bcl-2 also abrogated
      apoptosis induction following ultraviolet irradiation in HaCaT-ras/bcl-2
      organotypic cultures. Organotypic keratinocyte culture represents a valuable in
      vitro system to evaluate the impact of individual molecular genetic alterations
      on the coordinate regulation of cell proliferation, differentiation, and cell
      death.

PMID- 11231310
TI  - Identification of cDNA encoding a serine protease homologous to human complement
      C1r precursor from grafted mouse skin.
AB  - We isolated a cDNA clone from grafted mouse skin that encodes a serine protease
      homologous to human C1r. The C1r protease is involved in the activation of the
      first component of the classical pathway in the complement system. In order to
      identify novel transcripts whose expression is regulated in grafted mouse skin,
      we first performed differential display reverse transcription polymerase chain
      reaction analysis and obtained 18 partial cDNA clones whose protein products are
      likely to play an important role in allograft rejection. One of these showed
      significant sequence homology with human complement C1r precursor. The other
      clones displayed no homology to any known sequences, however. Northern blot
      analysis demonstrated that the level of this transcript was upregulated in day 8
      postgrafted skin. The full-length cDNA 2121 nucleotides in length obtained from
      screening a mouse skin cDNA library contained a single open reading frame
      encoding 707 amino acid residues with a calculated molecular weight of 80,732 Da.
      Its deduced amino acid sequence revealed an 81% identity and 89% similarity to
      the human C1r counterpart. In particular, mouse C1r contained His501, Asp559, and
      Ser656, which were conserved among this group of serine proteases. This protein
      was thus designated as mouse C1r. We have expressed a truncated fragment of C1r
      protein without the N-terminal hydrophobic sequence in Escherichia coli and
      generated a polyclonal antibody against it. Subsequent immunohistochemical
      analysis confirmed that mouse C1r was significantly expressed 8 d after the skin
      graft in both allografted and autografted skins, compared with normal skins.
      These collective data suggest that a component of the complement system, C1r,
      might contribute to the graft versus host immune responses in mice.

PMID- 11231311
TI  - Attenuated total reflection-Fourier transform infrared spectroscopy as a possible
      method to investigate biophysical parameters of stratum corneum in vivo.
AB  - We investigated the use of attenuated total reflection-Fourier transform infrared
      spectroscopy as a method to study differences in the molecular components of
      human stratum corneum in vivo. These variations as a function of the anatomic
      site and of the depth into its layered structure are important to understand the
      biology and physiology of the tissue. In this preliminary study we have
      investigated spectroscopic changes in 18 healthy individuals. Total reflection
      Fourier transform infrared spectroscopy represents a potentially powerful tool to
      study biophysical properties of surfaces. We observed that, in vivo, biophysical
      parameters of the stratum corneum (such as hydration, lipid composition, and
      conformation of the aliphatic chains) are indeed dependent on the anatomic site.
      As in total reflection-Fourier transform infrared spectroscopy experiments the
      penetration depth of the evanescent field into the stratum corneum is comparable
      with the thickness of a layer of corneocytes, this technique can be used to
      follow the distribution of lipids, water, and proteins as a function of depth
      into the tissue. We found that, in vivo, these molecular components are non
      uniformly distributed, in agreement with the presence of water and lipid
      reservoirs as observed with ex vivo ultrastructural investigations. Composition
      and conformational order of lipids are also a function of depth into the stratum
      corneum. Finally we compared the in vivo superficial hydration measured using the
      infrared absorption of the OH stretch of water, with the hydration measured using
      the Skicon hygrometer. Our results indicate that total reflection-Fourier
      transform infrared spectroscopy might be useful to measure important chemical and
      biophysical parameters of stratum corneum in vivo.

PMID- 11231312
TI  - Expression of mast cell growth modulating and chemotactic factors and their
      receptors in human cutaneous scars.
AB  - In order to explore possible mechanisms involved in the previously documented
      turnover of mast cell subpopulations in human cutaneous scars, we have examined
      selected factors known to stimulate and/or modulate mast cell hyperplasia (SCF,
      NGF, TGFbeta1, GM-CSF) and their receptors in human cutaneous scar tissue. On
      immunohistochemistry, numbers of SCF- and TGFbeta1-positive cells were
      significantly increased in the epidermis and throughout the dermis in scars (n =
      27) of varying ages (4-369 d old), compared with normal skin (n = 12).
      Furthermore, TRbetaRI, II, and the NGF-p75 receptors were significantly increased
      in the epidermis, TRbetaRI and NGF-TrkA throughout the dermis, and TRbetaRII, NGF
      p75, and GM-CSFR only in the mid- and lower dermis of scars. NGF and GM-CSF
      expression was in contrast scarce and weak, with no differences between normal
      skin and scars. In tissue extracts, mRNA levels of SCF, TGFbeta1, TRbetaI and II,
      and both NGF-receptors, but not GM-CSFR, were significantly increased as well.
      TRbetaI and II were identified in up to 90% and 83%, respectively, of isolated
      normal skin mast cells on flow cytometry, and GM-CSFR and NGFR-p75 were
      identified on 70% and 73%, respectively, of avidin-positive normal mast cells on
      double immunofluorescence microscopy. As described before for the SCF receptor
      KIT, GM-CSFR and NGFR-p75 were partly or entirely downregulated on avidin
      positive mast cells in scars. The marked upregulation of TGFbeta1, its type I and
      II receptors, and SCF suggest that these factors play a major role in the
      orchestration of mast cell increase in human cutaneous scars whereas the role of
      NGF and GM-CSF is less clear, despite the significant upregulation of their
      receptors.

PMID- 11231313
TI  - The level of prosaposin is decreased in the skin of patients with psoriasis
      vulgaris.
AB  - Ceramides are the most abundant lipids constituting the intercellular matrix of
      the skin stratum corneum and their critical role in skin homeostasis has been
      extensively documented. Their concentration in the skin highly depends on the
      rate of availability of the enzymes involved in ceramide generation. The aim of
      this study was to investigate whether the concentration of prosaposin was altered
      in the skin of patients with psoriasis vulgaris. Prosaposin, the precursor of
      saposins (sphingolipid activator proteins), was measured in lesional and
      nonlesional skin of psoriatic patients and in normal skin from surgical patients,
      both at the mRNA and at the protein level. Densitometric analysis of reverse
      transcriptase-polymerase chain reaction bands separated by gel-electrophoresis
      showed a progressive decrease of prosaposin mRNA expression in nonlesional and
      lesional psoriatic skin, being substantially decreased in lesional psoriatic skin
      compared with normal control skin. Immunohistochemical analysis showed a
      significant decrease of prosaposin level in the stratum corneum of psoriatic
      lesional skin (both in active-type and in chronic-type plaque) compared with
      nonlesional and with normal skin (p < 0.01), and in psoriatic nonlesional skin
      compared with normal control (p < 0.05). Immunolocalization of sphingomyelinase
      in lesional and nonlesional psoriatic skin showed a decrease in the level of this
      enzyme in the stratum corneum of psoriatic lesional, compared with nonlesional
      skin. These results support the concept that disturbance of epidermal barrier
      function caused by derangement in ceramide generation can be crucial for the
      development of psoriatic skin diseases.

PMID- 11231314
TI  - CD1a molecules traffic through the early recycling endosomal pathway in human
      Langerhans cells.
AB  - In this work, we studied the localization and traffic of CD1a molecules in human
      epidermal Langerhans cells and the ability of these cells to stimulate CD1a
      restricted T cell clones. We found that CD1a was spontaneously internalized into
      freshly isolated Langerhans cells, where it was rapidly distributed to the
      early/sorting endosomes and then to the early/recycling endosomes. In the latter
      compartments, CD1a colocalized with Rab11, a small GTPase known to be involved in
      the recycling of transmembrane proteins from early endosomes to the cell surface.
      In the steady state, intracellular CD1a was mainly located in Rab11+ recycling
      endosomal compartments. When endocytosis was blocked, intracellular CD1a moved
      rapidly from the early/recycling endosomes to the cell surface where it
      accumulated. The resultant increase in the cell surface expression of CD1a
      enhanced the capacity of Langerhans cells to stimulate a CD1a-restricted T cell
      clone. These findings are consistent with a dynamic exchange of CD1a between
      recycling compartments and the plasma membrane and suggest that the antigen
      presenting function of CD1a depends on its traffic through the early/recycling
      endosomal pathway.

PMID- 11231315
TI  - Differential expression of functional guanylyl cyclases in melanocytes: absence
      of nitric-oxide-sensitive isoform in metastatic cells.
AB  - Nitric oxide (NO) is a reactive endogenous molecule with multiple functions and
      its cellular signaling activity is mainly mediated by activation of the soluble
      isoform of guanylyl cyclase, a heterodimeric (alpha/beta) hemeprotein. The
      expression of the NO-sensitive soluble isoform of guanylyl cyclase was studied in
      various cultured melanocytic cells by measuring the accumulation of guanosine
      3',5'-cyclic monophosphate in the presence and absence of NO donors. Here we
      report that 3-morpholino-sydnonimine, a donor of NO redox species, and (Z)-1-[2-
      (2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate, a direct NO
      donor, induced a 20-fold increase in intracellular guanosine 3',5'-cyclic
      monophosphate in nonmetastatic melanoma cells and normal melanocytes in culture
      that could be related to cellular melanin content in a concentration-dependent
      manner. The increased intracellular guanosine 3',5'-cyclic monophosphate was due
      to stimulation of the activity of soluble guanylyl cyclase as such increase was
      completely abolished by using a specific inhibitor of soluble guanylyl cyclase.
      The involvement of functional soluble guanylyl cyclase was further confirmed by
      the presence of alpha1 and beta1 subunits in these cells at both mRNA and protein
      levels. In contrast, none of the NO donors induced guanosine 3',5'-cyclic
      monophosphate production in metastatic melanoma cells, which could be attributed
      to the absence of the beta1 subunit that is essential for catalytic activity of
      the soluble isoform of guanylyl cyclase. Metastatic melanoma cells produced
      higher levels of intracellular guanosine 3',5'-cyclic monophosphate in response
      to natriuretic peptides than other cell types, however, due to upregulation of
      membrane-bound guanylyl cyclase activities, but they are less pigmented or
      unpigmented. The present finding suggests that NO signaling in association with
      melanogenesis is dependent on the soluble isoform of guanylyl cyclase, whereas
      absence of soluble guanylyl cyclase but the presence of membrane-bound guanylyl
      cyclase correlates with the metastatic behavior of melanoma cells.

PMID- 11231316
TI  - Fibroblast matrix gene expression and connective tissue remodeling: role of
      endothelin-1.
AB  - This study examines endothelin-induced modulation of extracellular matrix
      synthesis and remodeling by fibroblasts, and its potential role in the
      pathogenesis of systemic sclerosis (scleroderma). Endothelin-1 promoted
      fibroblast synthesis of collagen types I and III, but not fibronectin, by a
      mechanism dependent upon both ETA and ETB receptors. Conversely, endothelin-1
      inhibited both protein expression of matrix metalloproteinase 1 and zymographic
      activity exclusively via ETA receptors. A dual regulatory role for endothelin-1
      in transcriptional regulation was suggested by the ability of endothelin-1 to
      enhance steady-state levels of collagen mRNA and activate the proalpha2(I)
      collagen (Col1a2) promoter, but in contrast to reduce matrix metalloproteinase 1
      transcript expression and suppress transcription of a human matrix
      metalloproteinase 1 promoter reporter construct in transient transfection assays.
      Although endothelin-1 significantly enhanced remodeling of three-dimensional
      collagen lattices populated by normal fibroblasts, this was not observed for
      lattices populated by systemic sclerosis fibroblasts. Promotion of matrix
      remodeling was dependent upon ETA receptor expression and was blocked by specific
      inhibitors of tyrosine kinases or protein kinase C. Reverse transcriptase
      polymerase chain reaction, S1 nuclease, and functional cell surface binding
      studies showed that normal and systemic sclerosis fibroblasts express both ETA
      and ETB receptors (predominantly ETA), but that ETA receptor mRNA levels and ETA
      binding sites on fibroblasts cultured from systemic sclerosis skin biopsies are
      reduced by almost 50%. Endothelin-1 is thus able to induce a fibrogenic phenotype
      in normal fibroblasts that is similar to that of lesional systemic sclerosis
      fibroblasts. Moreover, reduced responsiveness to exogenous endothelin-1 in
      systemic sclerosis suggests that downstream pathways may have already been
      activated in vivo. These data further implicate dysregulated endothelin-receptor
      pathways in fibroblasts in the pathogenesis of connective tissue fibrosis.

PMID- 11231317
TI  - Pancreatitis associated protein I (PAP-I) alters adhesion and motility of human
      melanocytes and melanoma cells.
AB  - Pancreatitis associated protein I is a secretory stress protein first
      characterized in pancreas during pancreatitis but also expressed in several
      tissues including hepatic, gastric, and colon cancer. Its concentration in serum
      can be significant. The relationship of pancreatitis associated protein I to skin
      cancers was investigated in normal melanocytes, melanoma tumors, and melanoma
      cell lines. None of them expressed pancreatitis associated protein I, even after
      stress induction. Adenovirus-mediated pancreatitis associated protein I
      expression, however, reduced cell adhesion to laminin-1 and fibronectin with a
      loss of integrin participation. Pancreatitis associated protein I expression
      stimulated haptotactic and directed migrations of some melanoma cells, but only
      directed migration was activated in normal melanocytes. Importantly, directed
      migration and spreading on fibronectin of the responsive melanoma cells were also
      enhanced when purified rat pancreatitis associated protein I was added to the
      culture medium of noninfected cells. This indicates that effects in infected
      cells were elicited by pancreatitis associated protein I after its secretion.
      Exogenous pancreatitis associated protein I can therefore modify the adhesion and
      motility of normal and transformed melanocytes, suggesting a potential
      interaction with melanoma invasivity.

PMID- 11231318
TI  - In vivo confocal Raman microspectroscopy of the skin: noninvasive determination
      of molecular concentration profiles.
AB  - Confocal Raman spectroscopy is introduced as a noninvasive in vivo optical method
      to measure molecular concentration profiles in the skin. It is shown how it can
      be applied to determine the water concentration in the stratum corneum as a
      function of distance to the skin surface, with a depth resolution of 5 microm.
      The resulting in vivo concentration profiles are in qualitative and quantitative
      agreement with published data, obtained by in vitro X-ray microanalysis of skin
      samples. Semi-quantitative concentration profiles were determined for the major
      constituents of natural moisturizing factor (serine, glycine, pyrrolidone-5
      carboxylic acid, arginine, ornithine, citrulline, alanine, histidine, urocanic
      acid) and for the sweat constituents lactate and urea. A detailed description is
      given of the signal analysis methodology that enables the extraction of this
      information from the skin Raman spectra. No other noninvasive in vivo method
      exists that enables an analysis of skin molecular composition as a function of
      distance to the skin surface with similar detail and spatial resolution.
      Therefore, it may be expected that in vivo confocal Raman spectroscopy will find
      many applications in basic and applied dermatologic research.

PMID- 11231319
TI  - Testosterone perturbs epidermal permeability barrier homeostasis.
AB  - Although there are no known gender-related differences in permeability barrier
      function in adults, estrogens accelerate whereas testosterone retards barrier
      development in fetal skin, and male fetuses demonstrate slower barrier
      development than female littermates. Moreover, prenatal administration of the
      androgen receptor antagonist, flutamide, equalizes developmental rates in male
      and female fetuses. Therefore, we evaluated the effects of changes in
      testosterone on barrier homeostasis in adult murine and human skin. Hypogonadal
      mice (whether by castration or by treatment with systemic flutamide) displayed
      significantly faster barrier recovery at 3, 6, and 12 h than did controls, and
      testosterone replacement slowed barrier recovery in castrated mice. Moreover,
      testosterone directly effects the skin, as topical flutamide also accelerated
      barrier recovery in normal male mice. These findings appear to be of physiologic
      significance, since prepubertal male mice (age 5 wk) displayed accelerated
      barrier recovery in comparison with adult postpubertal (11 wk) males. These
      studies also appear to be relevant for humans, as a hypopituitary human subject
      demonstrated repeated changes in barrier recovery in parallel with peaks and
      nadirs in serum testosterone levels during intermittent testosterone replacement.
      Mechanistic studies showed that differences in epidermal lipid synthesis do not
      account for the testosterone-induced functional alterations. Instead, epidermal
      lamellar body (LB) formation and secretion both decrease, resulting in decreased
      extracellular lamellar bilayers in testosterone-replete animals. These studies
      demonstrate that fluctuations in testosterone modulate barrier function, and that
      testosterone repletion can have negative consequences for permeability barrier
      homeostasis.

PMID- 11231320
TI  - Polymorphism of the androgen receptor gene is associated with male pattern
      baldness.
AB  - The common heritable loss of scalp hair known as male pattern baldness or
      androgenetic alopecia affects up to 80% of males by age 80. A balding scalp is
      characterized by high levels of the potent androgen dihydrotestosterone and
      increased expression of the androgen receptor gene. To determine if the androgen
      receptor gene is associated with male pattern baldness, we compared allele
      frequencies of the androgen receptor gene polymorphisms (StuI restriction
      fragment length polymorphism and two triplet repeat polymorphisms) in cases with
      cosmetically significant baldness (54 young and 392 older men) and controls (107
      older men) with no indication of baldness. The androgen receptor gene StuI
      restriction site was found in all but one (98.1%) of the 54 young bald men (p =
      0.0005) and in 92.3% of older balding men (p = 0.000004) but in only 76.6% of
      nonbald men. The combination of shorter CAG and GGC triplet repeat lengths was
      also more prevalent in bald men (p = 0.03). The ubiquity of the androgen receptor
      gene StuI restriction site, and higher incidence of shorter triplet repeat
      haplotypes in bald men suggests that these markers are very close to a functional
      variant that is a necessary component of the polygenic determination of male
      pattern baldness. Functional mutation in or near the androgen receptor gene may
      explain the reported high levels of expression of this gene in the balding scalp.

PMID- 11231321
TI  - Deletion of exons 1-5 of the STS gene causing X-linked ichthyosis.
AB  - X-linked ichthyosis is an inherited disorder due to steroid sulfatase deficiency.
      It is clinically characterized by dark, adhesive, and regular scales of the skin.
      Most X-linked ichthyosis patients present large deletions of the STS gene and
      flanking markers; a minority show a point mutation or partial deletion of the STS
      gene. In this study we analyzed the STS gene in a family with simultaneous
      occurrence of X-linked ichthyosis and ichthyosis vulgaris. X-linked ichthyosis
      diagnosis was confirmed through steroid sulfatase assay in leukocytes using 7
      [3H]-dehydroepiandrosterone sulfate as a substrate. Exons 1, 2, 5, and 6-10, and
      the 5' flanking markers DXS1130, DXS1139, and DXS996 of the STS gene were
      analyzed by polymerase chain reaction. X-linked ichthyosis patients of the family
      (n = 4 males) had undetectable levels of STS activity (0.00 pmol per mg protein
      per h). The DNA analysis showed that only exons 6-10 and the 5' flanking markers
      of the STS gene were present. We report the first partial deletion of the STS
      gene spanning exons 1-5 in X-linked ichthyosis patients.

PMID- 11231322
TI  - Treatment of peripheral blood mononuclear cells with 8-methoxypsoralen plus
      ultraviolet A radiation induces a shift in cytokine expression from a Th1 to a
      Th2 response.
AB  - Treatment with 8-methoxypsoralen plus ultraviolet A radiation and extracorporeal
      photochemotherapy (photopheresis) are widely used for the treatment of psoriasis
      and other inflammatory skin diseases, graft-versus-host disease, and mycosis
      fungoides. As the ratio of Th1 and Th2 cells appears to be critical for
      pathogenesis and progression of these disorders the effect of psoralen plus
      ultraviolet A on Th1 and Th2 cytokine production by CD4+ lymphocytes was
      investigated. Human peripheral blood lymphocytes were incubated in the presence
      of anti-CD3, rh-IL2, and rh-IL4 for 48 h. After subsequent stimulation with rh
      IL2 and rh-IL4 for 72 h cells were treated with 8-methoxypsoralen (100, 500, 1000
      ng per ml) plus ultraviolet A (2 J per cm2) and incubated for a further period of
      5 h in the presence of ionomycine, phorbol-12-myristate acetate and monensin.
      Fluorescence-activated cell sorter analysis revealed a significant reduction of
      interleukin-2- and interferon-gamma-producing CD4+ cells upon psoralen plus
      ultraviolet A treatment depending on the concentration of 8-methoxypsoralen. In
      contrast, interleukin-4-producing CD4+ cells were increased, indicating a shift
      from Th1 to a Th2 cell cytokine profile upon psoralen plus ultraviolet A
      treatment. These results indicate that 8-methoxypsoralen photochemotherapy of
      lymphocytes is able to modulate their Th1/Th2 distribution. Inhibition of Th1
      cytokine expression by psoralen plus ultraviolet A might help to explain its
      beneficial effects in the treatment of Th1 dominated skin diseases.

PMID- 11231323
TI  - "Second hit" in sebaceous tumors from Muir-Torre patients with germline mutations
      in MSH2: allele loss is not the preferred mode of inactivation.
AB  - Muir-Torre syndrome is an autosomal-dominant inherited disorder predisposing to
      both sebaceous skin tumors and internal neoplasms. In a significant proportion of
      Muir-Torre syndrome patients skin tumors exhibit microsatellite instability as a
      hallmark of hereditary nonpolyposis colorectal cancer. Most individuals
      predisposed to hereditary nonpolyposis colorectal cancer harbor a germline
      mutation in the DNA mismatch repair genes MSH2 or MLH1. In Muir-Torre syndrome
      the vast majority of germline mutations have been identified in MSH2.
      Microsatellite instability in tumor tissue develops after somatic inactivation of
      the corresponding second mismatch repair allele ("second hit"). So far, the
      mechanisms of somatic inactivation of the second allele in microsatellite
      instability positive tumors from patients with known mismatch repair germline
      mutations are not well understood. We examined whether allele loss (loss of
      heterozygosity) is a frequent mechanism for inactivation of the second MSH2
      allele in a sample of nine microsatellite instability positive skin tumors from
      eight unrelated Muir-Torre patients with known MSH2 germline mutations. Loss of
      heterozygosity was determined using microsatellite markers or heteroduplex
      analysis, respectively. Only one of the nine skin tumors exhibited loss of
      heterozygosity at the MSH2 locus. Thus, we could show in a sample of sebaceous
      tumors from patients with genetically proven Muir-Torre syndrome that loss of
      heterozygosity most probably is not the preferred mode of somatic inactivation of
      the second MSH2 allele.

PMID- 11231324
TI  - Aberrant expression of adhesion molecules by Sezary cells: functional
      consequences under physiologic shear stress conditions.
AB  - Although aberrations in adhesion molecule expression by lymphoma cells have been
      reported, the functional consequences of these changes are unclear. Herein, we
      report a patient with Sezary syndrome whose malignant peripheral blood T cells
      were TCRVbeta17+. Malignant T cell adhesion molecule abnormalities included an
      80% downregulation of LFA-1 compared with normal controls and no detectable
      expression of alpha4 integrin. Under shear stress conditions, malignant T cells
      failed to arrest on recombinant ICAM-1 in the presence of chemokines and
      displayed an 80% decrease in the ability to arrest on TNF-alpha activated dermal
      microvascular endothelial cells compared with normal CD4+ memory T cells.
      Cutaneous lymphocyte-associated antigen expression was detected in approximately
      25% of malignant T cells in the peripheral blood, but was substantially less than
      this in TCRVbeta17+ T cells in the dermis. By contrast, > 95% of malignant T
      cells in peripheral blood expressed L-selectin (CD62L), and L-selectin ligand was
      detected in dermal blood vessels at affected skin sites. Compared with normal
      CD4+, malignant T cells attached and rolled 6-fold more efficiently on L-selectin
      ligand (p < 0.0001). Thus, despite aberrant expression of LFA-1 and functional
      defects in the ability to arrest on activated endothelial cells, malignant T
      cells in this patient entered skin and produced significant clinical disease. We
      propose a mechanism by which the upregulated expression of L-selectin and L
      selectin ligands may partially compensate for altered LFA-1 function.

PMID- 11231325
TI  - An intrinsic antibiotic mechanism in wounds and tissue-engineered skin.

PMID- 11231326
TI  - Coincident PTCH and BRCA1 germline mutations in a patient with nevoid basal cell
      carcinoma syndrome and familial breast cancer.

PMID- 11231327
TI  - Is screening of the candidate gene necessary in unrelated partners of members of
      families with Herlitz junctional epidermolysis bullosa?

PMID- 11231328
TI  - Multiple glomus tumors of the skin with male-to-male transmission over four
      generations.

PMID- 11231329
TI  - Leukaemia inhibitory factor (LIF) expression in skin from amyotrophic lateral
      sclerosis patients compared with skin from normal individuals: what is the
      function of LIF in the skin?

PMID- 11231331
TI  - Limited concordance between "oakmoss" and colophony in clinical patch testing.

PMID- 11231333
TI  - Staphylococcal colonization in atopic dermatitis treatment with topical
      tacrolimus (Fk506).

PMID- 11231334
TI  - Novel point mutations of the ATP2A2 gene in two Chinese families with Darier
      disease.

PMID- 11231335
TI  - Epidermolysis bullosa carrier frequencies in the US population.

PMID- 11231336
TI  - A peripheral blood T cell clone is a prognostic marker in mycosis fungoides.

PMID- 11231337
TI  - What is the difference between IgA nephropathy and Henoch-Schonlein purpura
      nephritis?
AB  - Henoch-Schonlein purpura nephritis (HSPN) and IgA nephropathy (IgAN) are
      considered to be related diseases since both can be encountered consecutively in
      the same patient, they have been described in twins, and bear identical
      pathological and biological abnormalities. Apart from the presence of extrarenal
      clinical signs found only in HSPN, other differences are noticed between the two
      diseases. The peak age ranges between 15 and 30 years for a diagnosis of IgAN,
      whereas HSPN is mainly seen in childhood. Nephritic and/or nephrotic syndromes
      are more often seen at presentation in HSPN. In contrast to IgAN, HSPN has been
      described in association with hypersensitivity. Endocapillary and extracapillary
      inflammations as well as fibrin deposits in the glomerulus are more frequent in
      HSPN. No major biological differences have been found between the two illnesses,
      except for a larger size of circulating IgA-containing complexes (IgA-CC) and a
      greater incidence of increased plasma IgE levels in HSPN. As tissue infiltration
      by leukocytes is a major feature of HSPN vasculitis, a possible role of a more
      potent activation of the latter cells by IgA-CC and/or circulating chemokines in
      HSPN should be considered. Further studies are required to elucidate this
      possible mechanism as well as the role of hypersensitivity in HSPN.

PMID- 11231338
TI  - Molecular aspects of renal tubular handling and regulation of inorganic sulfate.
AB  - The renal proximal tubular reabsorption of sulfate plays an important role in the
      maintenance of sulfate homeostasis. Two different renal sulfate transport systems
      have been identified and characterized at the molecular level in the past few
      years: NaSi-1 and Sat-1. NaSi-1 belongs to a Na(+)-coupled transporter family
      comprising the Na(+)-dicarboxylate transporters and the recently characterized
      SUT1 sulfate transporter. NaSi-1 is a Na(+)-sulfate cotransporter located
      exclusively in the brush border membrane of renal proximal tubular and ileal
      cells. Recently, NaSi-1 was shown to be regulated at the protein and mRNA level
      by a number of factors, such as vitamin D, dietary sulfate, glucocorticoids and
      thyroid hormones, which are known to modulate sulfate reabsorption in vivo. The
      second member of renal sulfate transporters, denoted Sat-1, belongs to a family
      of Na+-independent sulfate transporter family comprising the DTDST, DRA and PDS
      genes. Sat-1 is a sulfate/bicarbonate-oxalate exchanger located at the
      basolateral membrane of proximal tubular epithelial cells and canalicular surface
      of hepatic cells. Contrary to NaSi-1, no physiological factor has been found to
      date to regulate Sat-1 gene expression. Both NaSi-1 and Sat-1 transporter
      activities are implicated in pathophysiological states such as heavy metal
      intoxication and chronic renal failure. This review focuses on recent
      developments in the molecular characterization of NaSi-1 and Sat-1 and the
      mechanisms involved in their regulation.

PMID- 11231339
TI  - Tubulointerstitial nephritis associated with a novel mitochondrial point
      mutation.
AB  - BACKGROUND: Nephropathy caused by mitochondrial disorders is a relatively newly
      recognized disease. Only a few cases have been reported in the literature, and
      most of them are proximal tubulopathy-presenting Fanconi syndrome. Here we report
      on a novel mutation in two familial cases of tubulointerstitial nephropathy
      associated with concentrating defect. METHODS: Renal biopsy specimens were
      examined by light microscopy and electron microscopy. Mitochondrial genomic DNA
      isolated from renal biopsy specimens was amplified by polymerase chain reaction
      (PCR) and sequenced in its entirety. The DNA sequences were analyzed by (1)
      comparing with the Anderson et al's mitochondrial sequences; (2) comparing with
      DNA sequences obtained from 97 human controls, including both healthy individuals
      and patients with renal diseases; and (3) comparing with the counterparts in 90
      different species. RESULTS: Dismorphic mitochondria with occasional
      intramitochondrial inclusions were found in the renal tubular epithelial cells. A
      novel mitochondrial point mutation was identified at the position 608, that is,
      the distal end of the anticodon stem of the tRNA(Phe) molecule. The A to G
      substitution at this position was not observed in 97 human controls and was found
      to be highly conserved in evolution. CONCLUSIONS: We have identified an A608G
      mutation of mitochondrial genome in two cases whose presentation include
      tubulointerstitial nephritis and stroke.

PMID- 11231340
TI  - p21(WAF1) and transforming growth factor-alpha mediate dietary phosphate
      regulation of parathyroid cell growth.
AB  - BACKGROUND: The parathyroid (PT) hyperplasia induced by renal failure can be
      further enhanced by high dietary phosphate (P) or completely abolished by P
      restriction. To identify potential mechanisms mediating these opposing effects of
      dietary P on PT growth, this study first focused on p21(WAF1) (p21) because high
      P reduces while low P enhances serum 1,25-dihydroxyvitamin D, whose potent
      antiproliferative properties result from the induction of p21. In addition to
      reducing p21, high P-induced PT growth could result from increased PT expression
      of the growth promoter transforming growth factor-alpha (TGF-alpha), known to be
      elevated in hyperplastic and adenomatous human PT glands. METHODS: The time
      course for dietary P regulation of PT expression of TGF-alpha and p21 was
      assessed for seven days after 5/6 nephrectomy in rats and correlated with the
      degree of PT hyperplasia and secondary hyperparathyroidism. RESULTS: In P
      restricted 5/6 nephrectomized rats, PT-p21 mRNA and protein increased by day 2,
      independent of changes in serum 1,25-dihydroxyvitamin D, and remained higher than
      in the high P counterparts for up to seven days. The PT hyperplasia of the high P
      group could not be attributed to a reduction of PT-p21 expression from normal
      control values. Instead, PT-TGF-alpha protein was higher in uremic rats compared
      with normal controls and increased further with high dietary P intake. PT levels
      of proliferating cell nuclear antigen (PCNA), an index of cell mitoses,
      correlated inversely with p21 and directly with TGF-alpha. Consistent with these
      findings, PT gland size and serum PT hormone levels, similar in both dietary
      groups at day 2, were higher in the high P group by day 5. Induction of p21 by
      low P and of TGF-alpha by high P was specific for the PT glands. Dietary P had no
      effect either on intestinal growth or p21 or TGF-alpha protein content.
      CONCLUSIONS: These findings suggest that low P induction of p21 could prevent PT
      hyperplasia in early uremia, whereas high P enhancement of TGF-alpha may function
      as an autocrine signal to stimulate growth further.

PMID- 11231341
TI  - Insulin regulation of protein translation repressor 4E-BP1, an eIF4E-binding
      protein, in renal epithelial cells.
AB  - BACKGROUND: Augmented protein translation by insulin involves activation of
      eukaryotic initiation factor 4E (eIF4E) that follows release of eIF4E from a
      heterodimeric complex by phosphorylation of its inhibitory binding protein, 4E
      BP1. We examined insulin regulation of 4E-BP1 phosphorylation in murine proximal
      tubular epithelial cells. METHODS AND RESULTS: Insulin (1 nmol/L) increased de
      novo protein synthesis by 58 +/- 11% (P < 0.001). Insulin also augmented 4E-BP1
      phosphorylation and phosphatidylinositol 3-kinase (PI 3-kinase) activity in
      antiphosphotyrosine immunoprecipitates. This could be prevented by PI 3-kinase
      inhibitors, Wortmannin, and LY294002. Insulin also activated Akt that lies
      downstream of PI 3-kinase. Rapamycin abrogated 4E-BP1 phosphorylation in response
      to insulin, suggesting involvement of mammalian target of rapamycin (mTOR), a
      kinase downstream of Akt. Insulin-stimulated phosphorylation of 4E-BP1 was also
      inhibited by PD098059, implying involvement of Erk-1/-2 mitogen-activated protein
      (MAP) kinase. An increase in Erk-1/-2 type MAP kinase activity by insulin was
      directly confirmed in an immunokinase assay and was found to be PI 3-kinase
      dependent. CONCLUSIONS: In proximal tubular epithelial cells, insulin augments 4E
      BP1 phosphorylation, which is PI 3-kinase and mTOR dependent. The requirement for
      Erk-1/-2 MAP kinase activation for 4E-BP1 phosphorylation by insulin suggests a
      cross-talk between PI 3-kinase and Erk-1/-2-type MAP kinase pathways.

PMID- 11231342
TI  - Relaxin decreases renal interstitial fibrosis and slows progression of renal
      disease.
AB  - BACKGROUND: Relaxin, a hormone of the insulin-growth factor family, promotes
      collagen remodeling. In rodent models of pulmonary and dermal fibrosis, relaxin
      reduced interstitial fibrosis. To study relaxin's effect in renal disease, we
      used the experimental bromoethylamine (BEA) model that leads to severe renal
      interstitial fibrosis, a decrease in glomerular filtration rate, and albuminuria
      at one month. METHODS: Rats were injected with BEA one week prior to implantation
      of an osmotic pump delivering relaxin (2 microg/hour) or vehicle continuously for
      28 days. RESULTS: BEA caused a significant decrease in creatinine clearance,
      which was partially prevented by relaxin. In the relaxin-treated BEA rats, serum
      creatinine was normal, and albumin excretion was slightly decreased. By
      morphometric measurement, relaxin administration was associated with a
      significant decrease in interstitial fibrosis at the corticomedullary junction.
      This was accompanied by a decrease in the number of ED-1 positive cells (an index
      of macrophage infiltration) and in the intensity of immunohistochemical staining
      for transforming growth factor-beta. This antifibrotic effect of relaxin did not
      appear to be mediated by systemic hemodynamic changes since the mean arterial
      pressure was not significantly different among the groups. CONCLUSIONS: Relaxin
      may have a useful application in decreasing interstitial fibrosis and thereby
      slowing the progression of renal disease.

PMID- 11231344
TI  - Escherichia coli-induced inducible nitric oxide synthase and cyclooxygenase
      expression in the mouse bladder and kidney.
AB  - BACKGROUND: The host response to urinary tract infection includes the production
      of different inflammatory mediators. We investigated the cellular localization
      and time course of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX
      2) expression in the mouse bladder and kidney after bacterial infection. METHODS:
      Experimental urinary tract infection in mice was established by intravesical
      inoculation of a clinical uropathogen Escherichia coli (E. coli) AD 110. Urine
      was collected at 6-, 12-, 24-, and 72-hours postinstillation, and the nitrite
      concentration was determined. The induction of iNOS and COX-2 was studied by
      immunohistochemistry and reverse transcription-polymerase chain reaction (RT
      PCR). RESULTS: Nitrite levels in the urine had increased threefold at 6 and 12
      hours postbacterial instillation. Bladders from mice instilled with AD 110, but
      not with phosphate-buffered saline, showed a large number of iNOS-- and COX-2-
      expressing inflammatory cells. The inflammatory cell activation peaked at 6 and
      12 hours postinstillation and had vanished by 72 hours. iNOS expression was
      detected in some urothelial cells after 24 and 72 hours, but COX-2 expression was
      not detected. In the kidney, infection activated an iNOS and COX-2 response, as
      shown by immunoreactivity in inflammatory cells at all time points. A strong
      epithelial iNOS response was observed in the renal pelvis at 12, 24, and 72 hours
      postinstillation, but COX-2 was not detected. Enhanced tissue expression of iNOS
      and COX-2 after bacterial instillation was also demonstrated by RT-PCR.
      CONCLUSIONS: E. coli AD 110 induced expression of iNOS and COX-2 in the urinary
      tract. Inflammatory cells expressed both iNOS-and COX-2, but epithelial cells
      expressed only iNOS and with a later onset than in the inflammatory cells. This
      suggests that the epithelial iNOS response is not caused by direct bacterial
      activation, but more likely is by mediators involved in the inflammatory
      response.

PMID- 11231343
TI  - T cells activate the tumor necrosis factor-alpha system during hemodialysis,
      resulting in tachyphylaxis.
AB  - BACKGROUND: The immunosuppressive state of hemodialysis (HD) patients is
      accompanied by activation of antigen-presenting cell-derived cytokines, for
      example, tumor necrosis factor-alpha (TNF-alpha), which are required for T-cell
      activation. To test whether an activated TNF-alpha system results in impaired T
      cell response in these patients, we analyzed parameters of their antigen
      presenting cell (APC) function (for example, TNF-alpha system) and T-cell
      function [for example, interleukin-2 (IL-2) system]. METHODS: By quantitative
      flow cytometry, the expression of the TNF-receptor 2 (TNF-R2 = CD120b) and the
      alpha and beta chain of the IL-2 receptor (IL-2R; CD25, CD122) was measured.
      Using reverse transcriptase-polymerase chain reaction, the mRNA for TNF-alpha, IL
      2, and IL-2R were determined. Phyto-hemagglutinin (PHA)- and IL-2-stimulated
      proliferation and cytokine production were measured. Biological activity of
      soluble receptors was measured by adding recombinant cytokines to the patient's
      plasma. RESULTS: CD120b expression was significantly increased in HD patients,
      whereas CD25 and CD122 was comparable to controls. In contrast to mRNA for IL-2
      and IL-2R, mRNA for TNF-alpha was increased in HD. This resulted in significantly
      increased TNF-alpha levels in HD patients. In peripheral blood of HD patients,
      high levels of soluble TNF-R (R1 and R2) and IL-2R were found. These receptors
      were capable of binding 40% of added TNF-alpha and 55% of added IL-2. PHA-induced
      TNF-alpha production by T cells from HD patients was significantly lower, while
      their PHA-stimulated IL-2 production and proliferation capacity by T cells were
      comparable to controls. CONCLUSIONS: We conclude that although the TNF-alpha
      system is activated during HD, the TNF-alpha production of T cells is impaired,
      suggesting that tachyphylaxis of T cells occurs for TNF-alpha, as their
      proliferative capacity and IL-2 production capacity do not imply an intrinsic T
      cell defect.

PMID- 11231345
TI  - Complement (C5b-9) induces DNA synthesis in rat mesangial cells in vitro.
AB  - BACKGROUND: The membrane attack complex C5b-9 causes injury in many forms of
      immune-mediated glomerular diseases characterized by mesangial cell (MC)
      proliferation and inhibiting C5b-9 decreases MC proliferation in vivo. Membrane
      insertion of sublytic quantities of the membrane attack complex of complement
      (C5b-9) is a potent stimulus for cell activation and the production of a variety
      of cytokines, growth factors, oxidants, matrix components, and other
      nephritogenic molecules. In vivo, a common response of MC to C5b-9--mediated
      injury is cell proliferation, an event closely linked to matrix expansion and
      sclerosis. In this study, we tested the hypothesis that C5b-9 might also serve as
      a mitogenic stimulus for MCs. METHODS: Rat MCs in vitro were exposed anti-Thy1
      antibody and 2% normal PVG serum (a complement source) to induce sublytic C5b-9
      attack and DNA synthesis and cell number were measured. Control MCs were exposed
      to antibody and C6-deficient PVG serum. RESULTS: Sublytic C5b-9--induced injury
      to MCs is sufficient to induce DNA synthesis. Furthermore, C5b-9 augmented DNA
      synthesis induced by platelet-derived growth factor (PDGF) and 5% fetal calf
      serum. C5b-9--induced DNA synthesis was reduced by inhibiting reactive oxygen
      species (ROS) with superoxide dismutase and catalase, but not by neutralizing the
      mitogenic growth factors PDGF and basic fibroblast growth factor (bFGF).
      CONCLUSIONS: This study demonstrates that C5b-9 may directly increase DNA
      synthesis in cultured MCs, which are mediated in part by the release of ROS, and
      that C5b-9 also augments DNA synthesis induced in MCs by other known mitogens.

PMID- 11231346
TI  - In vitro decrease of glomerular heparan sulfate by lymphocytes from idiopathic
      nephrotic syndrome patients.
AB  - BACKGROUND: Lymphocytes are involved in the physiopathologic mechanism of
      idiopathic nephrotic syndrome (INS). We have recently demonstrated that plasma
      from patients with INS decreases human glomerular epithelial cell (GEC)
      glycosaminoglycans (GAGs), particularly heparan sulfates (HS) in vitro. In this
      study we investigate the effect of peripheral blood lymphocytes (PBL) from INS
      patients on glomerular cell GAG and HS. METHODS: Human GECs were cultured with
      total peripheral blood mononuclear cells (PBMCs), PBL, and monocytes from
      patients and controls. The amounts of GAG and HS were assessed using a cationic
      membrane after metabolic labeling. RESULTS: In coculture with GECs, mononuclear
      cells from controls decreased total epithelial cell GAG (-30% with PBMC, P <
      0.05; -25% with PBL, P < 0.02; -19% with monocytes, P < 0.05). Particularly HSs
      were decreased (-36% with PBMC, P < 0.05; -27% with PBL, P < 0.02; and -19% with
      monocytes, P < 0.05). When GECs were in coculture with PBL from INS patients, the
      decrease in GAG and HS was significantly greater in comparison to control PBL (
      10%, P < 0.02; -10%, P < 0.02, respectively, for GAG and HS). Moreover,
      supernatants of stimulated PBMCs from patients decreased also GAG and HS in
      comparison with controls (-13%, P < 0.02; -15%, P < 0.02, respectively, for GAG
      and HS). CONCLUSION: These data provide direct evidence that PBLs from INS
      patients are able to decrease GEC HS as previously shown with plasma from
      patients. This might be instrumental in the onset of albuminuria.

PMID- 11231347
TI  - Activation of nuclear factor-kappa B by podocytes in the autologous phase of
      passive Heymann nephritis.
AB  - BACKGROUND: The present study examined whether activation of nuclear factor-kappa
      B (NF-kappa B) occurs within podocytes in passive Heymann nephritis (PHN) and
      contributes to the pathogenesis of proteinuria. METHODS: Electrophoretic mobility
      shift assays (EMSAs) were used to detect NF-kappa B activation, and supershift
      assays were used to determine the subunits involved. Localization of the
      activated NF-kappa B subunit p50 was performed by immunohistochemistry.
      Expression of the NF-kappa B-dependent genes interleukin-1 beta (IL-1 beta) and
      matrix metalloproteinase-9 (MMP-9) were determined by reverse transcription
      polymerase chain reaction and, for IL-1 beta, immunohistochemistry. To inhibit
      activation of NF-kappa B in vivo, pyrrolidone dithiocarbamate (PDTC) was
      administered for 10 days following induction of PHN. RESULTS: Glomerular nuclear
      extracts from rats with PHN showed increased NF-kappa B binding activity in
      comparison to normal rats. The major Rel/NF-kappa B proteins in these activated
      complexes were p65 and p50. Immunohistochemistry showed that nuclear
      translocation of p50 occurred predominantly within podocytes. IL-1 beta mRNA was
      increased in the PHN rats, and increased IL-1 beta protein was localized
      predominantly to podocytes by immunohistochemistry. To investigate whether
      activation of NF-kappa B is involved in the pathogenesis of proteinuria, PDTC was
      administered to rats with PHN. Electrophoretic mobility shift assays of
      glomerular nuclear extracts showed a significant reduction in NF-kappa B binding
      activity in the PDTC-treated rats with a striking reduction in MMP-9 mRNA.
      Compared with control rats, there was a significant reduction in albuminuria at
      days 15 (P < 0.001) and 20 (P < 0.001) when PHN was induced with a suboptimal
      dose of anti-Fx1A antiserum. There was no detectable difference in the systemic
      immune response to sheep Ig in the treated rats. CONCLUSIONS: These data show
      that NF-kappa B is activated within podocytes in PHN and suggest that it
      contributes to autologous phase proteinuria. The critical genes regulated by NF
      kappa B in the podocyte have not yet been determined, but may include MMP-9.

PMID- 11231348
TI  - Role of polymeric Tamm-Horsfall protein in cast formation: oligosaccharide and
      tubular fluid ions.
AB  - BACKGROUND: In acute tubular necrosis (ATN), distal tubules are obstructed by
      casts formed by tubular debris, cells, and Tamm-Horsfall protein (THP). Since
      there are Arginine-Glycine-Aspartate (RGD) and Leucine-Aspartate-Valine (LDV)
      adhesive sequences in human THP, there may be direct integrin-mediated binding of
      tubular cells to THP. Alternatively, polymerization of THP may result in
      entrapment of the cells in its gel. METHODS: Adhesion of LLC-PK(1) cells to THP
      coated wells was directly measured. THP concentrate was dissolved in solutions
      which mimic urine from ATN (ATN-S), distal convoluted tubule (DCT-S), collecting
      duct (CD-S), and monomeric buffer (M buffer). THP was also denatured by either
      boiling or N-glycanase digestion. Gel formation of THP was then measured.
      Inhibition of LLC-PK(1) cell adhesion to collagen type I was measured with each
      solution, as well as after the collagen was pretreated with either monomeric
      (mTHP) or polymeric (pTHP) THP. The effect of pTHP on the settling rate of LLC
      PK(1) cells in suspension was also measured. RESULTS: LLC-PK(1) cells did not
      directly adhere to THP, a finding against integrin-mediated binding as a
      mechanism for in vivo tubular cell/THP cast formation. The high electrolyte
      concentration of ATN-S and CD-S, however, was associated with pTHP gel formation.
      Moreover, cells suspended in pTHP remained in suspension. In cell adhesion
      studies, mTHP attenuated cell adhesion by binding to the matrix, whereas pTHP
      attenuated cell adhesion by trapping cells in its gel. An active process was
      involved since both pTHP gel formation and attenuation of cell adhesion were
      abolished by boiling or oligosaccharide removal with N-glycanase digestion.
      CONCLUSIONS: With renal ischemia and proximal tubule cell shedding, ATN and
      collecting duct fluid composition enhance THP gel formation and thus favor
      tubular cast formation and obstruction. The present in vitro results indicate the
      importance of oligosaccharide residues in mediating the effect of the THP on gel
      formation and potential cast formation in ATN.

PMID- 11231349
TI  - Role of CD8(+) cells in the progression of murine adriamycin nephropathy.
AB  - BACKGROUND: Many studies have shown that interstitial inflammation in human and
      experimental renal disease is characterized by T-cell infiltration, but published
      data on the involvement of inflammatory cell subsets in progressive
      tubulointerstitial lesions are often conflicting. A previous study suggested a
      role for cytotoxic T lymphocytes in the damaging effect of CD4(+) T-cell
      depletion in murine adriamycin (ADR) nephropathy, a model of focal segmental
      glomerulosclerosis (FSGS), and tubulointerstitial inflammation. The aim of this
      study was to investigate the role of CD8(+) cells in this model. METHODS: Male
      BALB/c mice were treated with five intraperitoneal injections of anti-CD8
      monoclonal antibody (mAb), beginning from five days after ADR treatment, when
      overt proteinuria was established. Seven mice in each of groups A (ADR + mAb), B
      (ADR only), and C (saline treated, age matched) were sacrificed at week 6.
      Changes in renal function and histopathological features were assessed.
      Tubulointerstitial inflammation and glomerular inflammation were examined
      immunohistochemically. RESULTS: mAb treatment reduced CD8(+) cell levels to <2%
      of normal in spleen. Proteinuria in group A was no different from that in group B
      at week 6, but was markedly higher than in group C. Creatinine clearance was
      significantly ameliorated by anti-CD8 treatment (71.8 +/- 4.9 microL/min vs. 29.2
      +/- 2.8 in group B and 81.9 +/- 3.7 in group C). Morphometric analysis showed
      less FSGS in group A compared with group B (6.5 +/- 1.9 vs. 13.0 +/- 2.8, P <
      0.001), as well as less tubular atrophy (indicated by increased ratio of tubule
      cell height to tubular diameter, 0.25 +/- 0.24 in group A vs. 0.04 +/- 0.02 in
      group B, P < 0.05). CD8 depletion also reduced interstitial expansion (6.3 +/-
      2.2% vs. 16.4 +/- 3.1 in group B, P < 0.001) and fibrosis (P < 0.01). Macrophage
      infiltration in tubulointerstitium was less in group A than in group B (P =
      0.052). The number of interstitial CD4(+) cells appeared to increase after anti
      CD8 treatment, but was not statistically different between groups A and B.
      CONCLUSION: Anti-CD8 treatment protects against renal functional and structural
      injury in this murine model of chronic proteinuric renal disease.

PMID- 11231350
TI  - Streptococcal erythrogenic toxin B induces apoptosis and proliferation in human
      leukocytes.
AB  - BACKGROUND: Previous reports have shown the presence of erythrogenic toxin type B
      (ETB), apoptosis, proliferation, and leukocyte infiltration in biopsies from
      patients with acute poststreptococcal glomerulonephritis (APSGN). METHODS:
      Attempting to correlate the apoptotic and proliferative events with the
      interaction of ETB or its precursor (ETBP) with leukocytes, mononuclear
      leukocytes from 12 healthy subjects were cultured with ETB or ETBP to analyze the
      levels of apoptosis, proliferation, expression of modulatory apoptosis gene
      products, and oxidative metabolism. After four days of incubation, cells were
      assessed for apoptosis by morphological criteria, annexin V assay, and terminal
      deoxy transferase uridine triphosphate nick end-labeling (TUNEL) assay. The
      expression of regulatory apoptosis genes was assessed by relevant monoclonal
      antibodies; proliferation was by incorporation of radioactive thymidine; and
      oxidative metabolism was by oxidation of 2',7'-dichlorofuorescein diacetate to
      2',7'-dichlorofuorescein. Neutralization of Fas-L and cysteine protease activity
      of ETB were performed by incubation of ETB-treated leukocyte cultures with anti
      human Fas-L mAb or with E64, respectively. RESULTS: Elevated levels of apoptosis
      in ETBP/ETB-treated leukocytes were found when compared with controls:
      morphological criteria (P < 0.01), Annexin V (control, 5.01 +/- 0.61; ETBP, 10.60
      +/- 1.98%, P = 0.0005), and TUNEL (control, 12.5 +/- 2.6; ETBP, 20.56 +/- 3.06%,
      P = 0.001; ETB, 30.69 +/- 5.05%, P = 0.001). Increased expression of apoptosis
      was accompanied by increased expression of Fas (control, 20.15 +/- 5.28; ETBP,
      43.51 +/- 5.6%, P = 0.03; ETB, 47.16 +/- 5.54%, P = 0.01), Fas ligand (control,
      5.64 +/- 2.38; ETBP, 11.66 +/- 3.65%, P = 0.04; ETB, 16.39 +/- 5.05%, P = 0.02)
      and p53 products (control, 9.22 +/- 3.44; ETBP, 22.82 +/- 5.72%, P = 0.01; ETB,
      24.60 +/- 5.20%, P = 0.01). Treatment of ETB-leukocyte cultures with anti-human
      Fas-L exhibited 2.2-fold lower apoptosis expression. Treatment with E64
      significantly abrogated the apoptotic effect of ETB. There was no increment on
      leukocyte oxidative metabolism. Mononuclear leukocytes also showed elevated
      levels of proliferation when treated with different concentrations (from 50 to
      6.2 microg/mL) of streptococcal proteins (Stimulation index ranging: ETBP, 5.6 +/
      1.9 to 6.4 +/- 1.9; ETB, 9.9 +/- 2.8 to 13.9 +/- 3.8). CONCLUSIONS: These
      results delineate an additional pathway for the pathogenesis of APSGN related to
      the role of cationic streptococcal ETB or ETBP on the induction of apoptosis and
      proliferation during the course of the disease.

PMID- 11231351
TI  - Expression of osteopontin in gentamicin-induced acute tubular necrosis and its
      recovery process.
AB  - BACKGROUND: There is controversy regarding the exact localization and roles of
      osteopontin (OPN), a multipotential chemokine, in renal injury. There is little
      information on the expression and role of OPN in gentamicin-induced acute tubular
      necrosis (ATN) and its recovery process. METHODS: A severe ATN model was made
      using male Wistar rats by injecting gentamicin (150 mg/kg/day) for five days and
      limiting the provision of water. The expression and localization of OPN mRNA and
      protein, ED1 as a macrophage marker, proliferating cellular nuclear antigen
      (PCNA), CD44 as an OPN receptor, megalin as a proximal tubule marker, and their
      relationships to each other were examined from the early tubular necrotic period
      to the late recovery period by Northern blotting, in situ hybridization, and
      double immunohistochemical staining. RESULTS: In the gentamicin group, OPN mRNA
      and protein were expressed in only the PCNA-positive proliferating cortical
      distal tubules, not in the necrotic proximal tubules, until day 6 after the first
      administration, but were found markedly in PCNA-positive regenerative proximal
      and distal tubules on days 10, 15, and 30. The localization of PCNA-positive
      cells was almost always accompanied with the up-regulated expression of OPN using
      quantitative analysis (P < 0.01). CD44 expression was markedly up-regulated in
      the renal cortical tubular epithelium from days 6 to 30. In the control group, no
      expression of OPN and CD44 in the cortical area was found throughout the
      experimental period. CONCLUSIONS: These results suggested that OPN is related to
      the proliferation and regeneration of tubular epithelial cells after tubular
      damage.

PMID- 11231352
TI  - Depletion of CD4(+) T cells aggravates glomerular and interstitial injury in
      murine adriamycin nephropathy.
AB  - BACKGROUND: CD4(+) T cells play an important role in various types of immunologic
      renal disease, including lupus nephritis, IgA nephropathy, and crescentic
      glomerulonephritis. CD4(+) T cells are also major infiltrating lymphocytes in
      chronic tubulointerstitial inflammation associated with nonimmunological renal
      diseases. We suspected that CD4(+) T cells might contribute to disease
      progression and loss of renal function in chronic proteinuric renal disease
      (CPRD). To investigate this possibility, the effect of monoclonal antibody
      against CD4(+) lymphocytes (anti-CD4) was studied in a murine model (adriamycin
      nephropathy) of CPRD. METHODS: Adriamycin nephropathy was produced in male BALB/c
      mice by a single intravenous injection of adriamycin (11 mg/kg). Anti-CD4 was
      given by intraperitoneal injection following the development of proteinuria at
      days 5, 6, 7, 21, and 37 after adriamycin. After six weeks, renal function and
      histology were studied by histomorphometry, immunohistochemistry, and flow
      cytometry. RESULTS: Flow cytometric analysis showed a marked decrease in the
      number of CD4(+) T cells in blood and spleen of the antibody-treated animals (N =
      7, P < 0.01). Adriamycin plus CD4(+) depletion mice had significantly greater
      mesangial expansion, glomerular sclerosis, and interstitial expansion than the
      mice on adriamycin alone. Interstitial infiltration with macrophages and CD8(+)
      cells was significantly increased in adriamycin plus CD4(+) depletion mice.
      Creatinine clearance (17.5 +/- 0.54 vs. 29.2 +/- 0.89 microL/min, P < 0.001) was
      significantly worse in the adriamycin plus CD4(+) depletion mice than in
      adriamycin alone mice and correlated with histologic change in glomeruli and
      interstitium. CONCLUSIONS: Depletion of CD4(+) T cells promotes glomerular and
      interstitial injury in mice with established adriamycin nephropathy. These
      findings suggest that CD4(+) T cells have a protective role against the
      progression of adriamycin nephropathy.

PMID- 11231353
TI  - Polymorphisms of the glucose transporter (GLUT1) gene are associated with
      diabetic nephropathy.
AB  - BACKGROUND: Diabetic nephropathy (DN) is a major cause of morbidity and mortality
      in patients with type 1 diabetes mellitus. Recent studies suggest that genetic
      factors, including polymorphisms in the flanking region of the aldose reductase
      gene (5'ALR2), play an important role in the pathogenesis of nephropathy. Glucose
      transporter (GLUT1) activity has been implicated in renal hypertrophy and
      extracellular matrix formation in mesangial cells. The aim was to investigate the
      frequency of a polymorphism within the GLUT1 gene in 186 Caucasoid patients with
      type 1 diabetes and 104 normal controls. METHODS: Amplimers flanking the Xba-I
      polymorphic site in the second intron were employed to amplify DNA from subjects.
      The amplified DNA was restricted with endonuclease Xba-I, separated by gel
      electrophoresis, and visualized. In the absence of an Xba-I site, a fragment of
      1.1 kilobase was seen, whereas fragments of 0.9 and 0.2 were generated if the Xba
      I site was present. RESULTS: There was a highly significant increase in the
      frequency of the 1.1 allele in those patients with nephropathy (N = 70) compared
      with those with no proteinuria or retinopathy after 20 years of diabetes
      (uncomplicated N = 44, 61.4 vs. 40.9%, respectively, P < 0.001). The 1.1/1.1
      genotype was also significantly increased in the nephropathy group compared with
      the uncomplicated group of patients (37.1 vs. 13.6%, respectively, P < 0.01). The
      frequency of the 1.1/1.1 genotype was similar in 30 patients with retinopathy but
      not nephropathy when compared with the uncomplicated group of patients (13.6 vs.
      16.7%). Furthermore, only 8 out of 49 patients with DN had the Z+2 5'ALR2 DN
      "protective" allele and the 0.9 GLUT1 allele in contrast to 21 out of 39
      uncomplicated patients (P < 0.0002). CONCLUSION: These results suggest that the
      GLUT1 gene together with the aldose reductase gene are associated with
      susceptibility to DN in patients with type 1 diabetes.

PMID- 11231355
TI  - FAT is a component of glomerular slit diaphragms.
AB  - BACKGROUND: Slit diaphragms are intercellular junctions of podocytes of the renal
      glomerulus. The molecular composition of slit diaphragms is still elusive. Slit
      diaphragms are characterized by the presence of a wide intercellular space. The
      morphological feature is shared by desmosomes and adherens junctions, which
      contain members of the cadherin superfamily. Thus, we have hypothesized that some
      components of slit diaphragms belong to the cadherin superfamily. Consequently,
      we have isolated cDNA encoding FAT from reverse-transcribed (RT) glomerular cDNA
      by homology polymerase chain reaction (PCR) using primers based on conserved
      sequences in cadherin molecules. FAT is a novel member of the cadherin
      superfamily with 34 tandem cadherin-like extracellular repeats, and it closely
      resembles the Drosophila tumor suppressor fat. METHODS: Expression of FAT was
      examined in glomeruli of the adult rat kidney by the ribonuclease protection
      assay and in situ hybridization. To localize the FAT protein in podocytes
      minutely, we prepared affinity-purified antibody against FAT by immunizing
      rabbits against an oligopeptide corresponding to the C-terminal 20 amino acids.
      RESULTS: Expression of FAT mRNA was detected in total RNA from glomeruli. In situ
      hybridization revealed significant signals in podocytes. Western blot analysis
      using solubilized glomeruli showed a single band, in which the molecular weight
      was more than 500 kD. Immunostaining of cultured epithelial cells from rat kidney
      (NRK52E) revealed FAT accumulation in cell-cell contact sites. In the glomerulus,
      FAT staining was observed distinctly along glomerular capillary walls. Double
      label immunostaining using monoclonal antibody against slit diaphragms (mAb 5-1
      6) showed identical localization of anti-FAT antibody and mAb 5-1-6. Furthermore,
      the double-label immunogold technique with ultrathin cryosections demonstrated
      that gold particles for FAT cytoplasmic domain were located at the base of slit
      diaphragms labeled by mAb 5-1-6 and that the cytoplasmic domain of FAT
      colocalized with ZO-1, a cytoplasmic component associated with slit diaphragms.
      CONCLUSION: The molecular structure of FAT and its colocalization with 5-1-6
      antigen and ZO-1 indicate that FAT is a component of slit diaphragms.

PMID- 11231354
TI  - beta(2)-Microglobulin modified with advanced glycation end products delays
      monocyte apoptosis.
AB  - BACKGROUND: A local inflammatory reaction to beta(2)-microglobulin (beta(2)m)
      amyloid deposits by monocytes/macrophages is a characteristic histologic feature
      of dialysis-related amyloidosis (DRA). Since beta(2)m modified with advanced
      glycation end products (AGE-beta(2)m) is a major constituent of amyloid in DRA,
      we tested the hypothesis that AGE-beta(2)m affects apoptosis and phenotype of
      human monocytes. METHODS: Human peripheral blood monocytes were incubated with or
      without in vitro-derived AGE-beta(2)m, and their viability, extent of apoptosis,
      morphology, and function examined over the subsequent four days. RESULTS: AGE
      modified but not unmodified beta(2)m significantly delayed spontaneous apoptosis
      of human peripheral blood monocytes in adherent and nonadherent cultures. The
      effect of AGE-beta(2)m on monocytes apoptosis was time- and dose-dependent and
      was attenuated by a blocking antibody directed against the human AGE receptor
      (RAGE). There was no difference in effect between AGE-beta(2)m and that of AGE
      modified human serum albumin. Culture of monocytes with AGE-beta(2)m did not
      alter membrane expression of Fas or Fas ligand. Monocytes cultured with AGE
      beta(2)m underwent substantial changes in morphology similar to those observed
      when monocytes differentiate into macrophages. The cultured cells increased in
      size and vacuolization, and their content of beta-glucuronidase and acid
      phosphatase increased by 5- to 10-fold at day 4. Expression of the monocyte-
      macrophage membrane antigens HLA-DR, CD11b, and CD11c also increased at day 4.
      Although exhibiting phenotypic characteristics of macrophages, monocytes cultured
      with AGE-beta(2)m functioned differently than macrophages cultured with serum.
      Superoxide production in response to phorbol myristic acetate was maintained in
      monocytes cultured with AGE-beta(2)m, but declined with time in cells cultured
      with serum. Constitutive synthesis of tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1 beta (IL-1 beta) and prostaglandin E2 (PGE2) increased in monocytes
      cultured for four to six days with AGE-beta(2)m. CONCLUSIONS: These findings
      support a novel role for AGE-modified proteins such as AGE-beta(2)m that may
      contribute to the development of a local inflammatory response, with predominant
      accumulation of monocytes/macrophages, in DRA.

PMID- 11231356
TI  - Expression of the sodium iodide symporter in human kidney.
AB  - BACKGROUND: The human sodium iodide symporter (hNIS) is a transmembrane protein
      that mediates the active transport of iodide in the thyroid gland. Following
      cloning of NIS, NIS expression has been detected in a broad range of nonthyroidal
      tissues, suggesting that iodide transport in these tissues is conferred by the
      expression of functional NIS protein. METHODS: The aim of this study was to
      examine functional hNIS expression in kidney by reverse transcription-polymerase
      chain reaction (RT-PCR), ribonuclease protection assay (RPA),
      immunohistochemistry, and Western blot analysis accompanied by iodide
      accumulation studies in kidney cells. RESULTS: Using a pair of full-length hNIS
      specific oligonucleotide primers, RT-PCR followed by Southern hybridization
      revealed hNIS mRNA expression in normal human kidney tissue. The PCR products
      were subjected to automated sequencing and revealed full identity with the
      published human thyroid-derived NIS cDNA sequence. Furthermore, positive
      protected bands indicating the presence of hNIS mRNA were apparent in RPA gel
      lanes corresponding to human kidney cells as well as Chinese hamster ovary (CHO)
      cells stably transfected with hNIS cDNA and Graves' thyroid tissue.
      Immunohistochemical analysis of normal human kidney tissue using a mouse
      monoclonal hNIS-specific antibody showed marked hNIS-specific immunoreactivity
      confined to tubular cells, while no hNIS-specific immunoreactivity was detected
      in the glomeruli. NIS protein expression in human kidney cells was further
      confirmed by Western blot analysis. In addition, accumulation of (125)I was
      detected in human kidney cells in vitro and was shown to be sodium dependent and
      sensitive to perchlorate. CONCLUSIONS: Functional hNIS expression was
      demonstrated in the renal tubular system, suggesting that renal iodide transport
      may be, at least in part, an active process driven by NIS.

PMID- 11231358
TI  - Renal perfusion and function in healthy African Americans.
AB  - BACKGROUND: Despite their increased risk of nephropathy, remarkably little is
      known about renal perfusion and function in healthy African Americans. METHODS:
      We enrolled 32 healthy African Americans and compared renal perfusion and
      function in 82 age-matched healthy Caucasians. Studies were performed on a diet
      containing 200 mmol of sodium and 100 mmol of potassium per day. In a separate
      study of 28 subjects, 10 African American and 18 Caucasians, the contribution of
      the renin-angiotensin system was assessed by measuring renal hemodynamic
      responses to angiotension II (Ang II) and captopril. RESULTS: Although glomerular
      filtration rate (GFR) was similar, renal plasma flow (RPF) was significantly less
      in age-matched African Americans (568 +/- 18) than Caucasians (620 +/- 13
      mL/min/1.73 m(2), P = 0.0063). After captopril, African Americans had a sevenfold
      greater vasodilator response and a rise in RPF (35.3 +/- 4.9 vs. 4.9 +/- 12.4
      mL/min/1.73 m(2) in African Americans and Caucasians, respectively, P < 0.028).
      Ang II administration caused a significantly smaller vasoconstrictor response in
      African Americans (Ang II-induced fall in RPF, -97 +/- 18 vs. -150 +/- 9
      mL/min/1.73 m(2), P = 0.05), and angiotensin-converting enzyme (ACE) inhibition
      enhanced the response to Ang II in African Americans significantly. CONCLUSIONS:
      A reduction in RPF, blunting of the renal vascular response to Ang II, and an
      accentuated renal vasodilator response to captopril, which in turn corrects the
      blunting of responsiveness to Ang II, all suggest activation of the renin system
      in apparently healthy African Americans. As PRA was identical in Caucasians and
      African Americans, the findings suggest that it is the intrarenal-renin system
      that is activated in African Americans. This difference in normal control
      mechanisms could predispose to nephropathy.

PMID- 11231357
TI  - Gentamicin causes endocytosis of Na/Pi cotransporter protein (NaPi-2).
AB  - BACKGROUND: Renal toxicity is a major side-effect of aminoglycoside antibiotics
      and is characterized by an early impairment in proximal tubular function. In a
      previous study, we have shown that gentamicin administration to the rat causes an
      early impairment in sodium gradient-dependent phosphate (Na/Pi) cotransport
      activity. The purpose of our current study was to determine the molecular
      mechanisms of the impairment in Na/Pi cotransport activity, specifically the role
      of the proximal tubular type II Na/Pi cotransporter. METHODS: Rats were treated
      for one, two, and three days with two daily injections of 30 mg/kg body weight
      gentamicin or the vehicle. RESULTS: Gentamicin caused a progressive decrease in
      superficial cortical apical brush-border membrane (SC-BBM) Na/Pi cotransporter
      activity (856 +/- 93 in control vs. 545 +/- 87 pmol/mg BBM protein in 3-day
      gentamicin, P < 0.01). Western blot analysis showed a parallel and progressive
      decrease in SC-BBM Na/Pi cotransporter protein abundance, a 50% decrease after
      one day of treatment, a 63% decrease after two days of treatment, and an 83%
      decrease after three days treatment with gentamicin. In contrast, gentamicin
      treatment had no effect on Na/Pi cotransport activity or Na/Pi cotransporter
      protein abundance in BBM isolated from the juxtamedullary cortex (JMC-BBM).
      Immunofluorescence microscopy showed a major decrease in the expression of Na/Pi
      cotransporter protein in the apical membrane of the proximal convoluted tubule,
      with progressive intracellular accumulation of Na/Pi protein. Colocalization
      studies showed that in gentamicin-treated rats, Na/Pi protein was colocalized in
      the early endosomes and especially in the lysosomes. Northern blot analysis of
      cortical RNA interestingly showed no reduction in Na/Pi cotransporter mRNA
      abundance even after three days of gentamicin treatment. CONCLUSION: We conclude
      that gentamicin inhibits Na/Pi cotransport activity by causing a decrease in the
      expression of the type II Na/Pi cotransport protein at the level of the proximal
      tubular apical BBM and that inhibition of Na/Pi cotransport activity is most
      likely mediated by post-transcriptional mechanisms.

PMID- 11231359
TI  - Effects of sodium artesunate, a new antimalarial drug, on renal function.
AB  - BACKGROUND: Sodium artesunate is currently used in malaria treatment. Adverse
      effects of this drug have not been described, probably because they cannot be
      differentiated from malaria-related effects. METHODS: The effects on renal
      function of an acute infusion of sodium artesunate (12 mg/kg body weight) were
      studied in the rat with clearance techniques. We also evaluate the effect of
      sodium artesunate on chloride lumen-bath flux (Cl Jlb) in the isolated thick
      ascending limb of the loop of Henle (TALH) microperfused in vitro. RESULTS: Acute
      infusion of artesunate to the rat decreased inulin clearance, despite an increase
      in renal blood flow. These effects were associated with an increase in urinary
      excretion of sodium, chloride, potassium, and nitric oxide metabolites
      (NO(2)/NO(3)). In water-loaded animals, artesunate increased sodium and water
      distal delivery and decreased free water clearance (C(H(2)O)) factored for sodium
      and water delivery. Following hypertonic NaCl infusion, artesunate decreased free
      water excretion (Tc(H(2)O)) corrected by clearance of osmolarity (C(Osm)). In
      vitro, artesunate 10(-6) and 10(-3) mol/L added to bath solution decreased
      chloride lumen-bath flux in isolated rabbit TALH in a dose-dependent manner, with
      the threshold effect at 10(-4) mol/L. This effect was completely blocked by N(G)
      nitroL-arginine-metilester (L-NAME) 5 mmol/L. Artesunate 10(-4) mol/L added to
      the perfusion solution did not change Cl Jlb. CONCLUSION: These findings suggest
      that artesunate decreases glomerular filtration rate and increases renal blood
      flow and urinary excretion of Na, Cl, and K. These effects were due, at least in
      part, to the inhibition of Cl transport across cortical and medullary TALH, and
      were mediated by local production of nitric oxide, since it is associated with an
      increase in NO(2)/NO(3) urinary excretion and it is blocked by L-NAME in vitro.

PMID- 11231360
TI  - Renal hemodynamic response to maximal vasodilating stimulus in healthy older
      subjects.
AB  - BACKGROUND: It is still unclear whether age per se is associated with
      preservation of renal functional reserve, that is, of the increase in glomerular
      filtration rate (GFR) induced by appropriate vasodilating stimulus. METHODS: To
      gain insights into this issue, we evaluated the renal response to a maximal
      vasodilating stimulus, represented by the combined infusion of mixed amino acid
      solution (AA) and dopamine at renal dose (D), in 10 young subjects (median age of
      30 years, range of 19 to 32) and in 11 subjects of older age (median age of 67
      years, range of 65 to 76). Two further age-matched groups of young (N = 15) and
      older (N = 11) living kidney donors underwent renal needle biopsy immediately
      before nephrectomy to perform semiquantitative scoring (0 to 3) of
      arteriosclerosis in intrarenal arteries. All of the study subjects were
      nonsmokers with healthy status proven by extensive diagnostic evaluation
      excluding any risk factor of renal dysfunction. RESULTS: Basal renal plasma flow
      (RPF) and GFR were proportionally lower in older subjects (RPF, 361 +/- 29 vs.
      618 +/- 34 mL/min/1.73 m(2), P < 0.001; GFR, 79 +/- 4 vs. 127 +/- 5.8 mL/min/1.73
      m(2), P < 0.001). After AA + D, a significant increase of RPF and GFR was
      observed in both groups, but the older subjects exhibited a smaller percentage
      increment (RPF, 25.5 +/- 4.8 vs. 42.4 +/- 5.8, P < 0.05; GFR, 19.6 +/- 5.7 vs. +
      33.8 +/- 6.4, P < 0.05). Furthermore, the maximal vasodilating stimulus was not
      able to restore renal hemodynamics in older subjects to the level measured in
      young controls at baseline. Renal vascular resistances were higher (P < 0.05) in
      the older subjects both at baseline (0.19 +/- 0.02 vs. 0.09 +/- 0.004 mm
      Hg/mL/min) and after AA + D (0.14 +/- 0.01 vs. 0.06 +/- 0.004). Light microscopy
      examination detected the presence of a greater degree of arteriosclerosis at the
      level of interlobular and arcuate arteries (0.89 +/- 0.15 vs. 0.45 +/- 0.08) and
      interstitial fibrosis/tubular atrophy (1.18 +/- 0.13 vs. 0.53 +/- 0.13) in older
      than in young subjects. CONCLUSIONS: Therefore, aging has adverse effects on
      renal function despite the absence of any risk factor for renal disease,
      including chronic smoking: (1) GFR and RPF are lower, and (2) the renal response
      to maximal vasodilating stimulus is impaired. These aging-related alterations of
      renal hemodynamics are possibly due to organic lesions in renal vasculature.

PMID- 11231361
TI  - Nitric oxide in unilateral ureteral obstruction: effect on regional renal blood
      flow.
AB  - BACKGROUND: Ureteral obstruction (UO) is characterized by reduced blood flow and
      loss of tissue mass in the involved kidney(s). Vasoactive mediators interact to
      produce an initial hyperemia, followed by a sustained decrease in renal blood
      flow in the obstructed kidney. Nitric oxide (NO) has been shown to play a central
      role in the acute hyperemic response to UO. Its role in the reduced perfusion of
      prolonged UO is less studied. METHODS: Ureteral obstruction was achieved by
      ligation of the distal left ureter and maintained for 24 hours. Blood flow was
      studied in untreated animals and after the administration of the NO synthase
      (NOS) inhibitor N-mono-methyl L-arginine and the NO donor sodium nitroprusside.
      Tissue was collected for localization and quantitation of NOS. Serum and renal
      tissue L-arginine levels were measured in control and UO settings. RESULTS: Blood
      flow in the obstructed kidney diminished to approximately 50% of control values
      after 24 hours of UO. NOS blockade led to a further decrease in blood flow.
      Supplementation with exogenous nitrates restored renal blood flow to levels
      approaching control values. Serum and tissue L-arginine levels did not change
      with UO. NOS expression was seen to increase with increasing duration of
      obstruction, with staining most pronounced in the renal tubules. CONCLUSIONS: NO
      plays a vasodilatory role even in the hypoperfusion of prolonged UO. The
      administration of exogenous nitrates has a restorative effect on blood flow,
      suggesting therapeutic potential in UO.

PMID- 11231362
TI  - Chloride-sensitive renal microangiopathy in the stroke-prone spontaneously
      hypertensive rat.
AB  - BACKGROUND: In the stroke-prone spontaneously hypertensive rat (SHRSP) fed a low
      normal NaCl diet, we recently reported that supplemental KCl, but not KHCO(3) or
      K-citrate (KB/C), exacerbated hypertension and induced hyperreninemia and
      strokes. We now ask the following question: In these SHRSP, is either such
      selectively Cl(-)-sensitive hypertension or hyperreninemia a pathogenetic
      determinant of renal microvasculopathy? METHODS: SHRSPs were randomized to either
      supplemental KCl, KB/C, or nothing (control) at 10 weeks of age. Four and 14
      weeks afterward, we assessed renal microangiopathy histologically and measured
      plasma renin activity (PRA). From randomization, blood pressure was measured
      radiotelemetrically and continually; proteinuria was measured periodically.
      RESULTS: KCl, but not KB/C, amplified renal microangiopathy and proteinuria. Four
      weeks after randomization, when KCl initially exacerbated hypertension, renal
      microangiopathy, hyperproteinuria, and hyperreninemia had not yet occurred.
      However, across all groups, the increment of SBP at four weeks strongly predicted
      its final increment, severity of renal microangiopathy, proteinuria, and PRA 14
      weeks after randomization. Then, the severity of renal microangiopathy varied
      directly with the levels of systolic blood pressure (SBP; R(2) = 0.9, P <
      0.0001), PRA (R(2) = 0.7, P < 0.0001), and proteinuria (R(2) = 0.8, P < 0.0001)
      as continuous functions across all treatment groups. Renal creatinine clearance
      was greater with KB/C. CONCLUSIONS: In the SHRSP, (1) like cerebral
      microangiopathy, renal microangiopathy is selectively Cl(-) sensitive and hence,
      systemic microangiopathy is as well; (2) Cl(-) likely amplifies microangiopathy
      by exacerbating hypertension and possibly also by increasing PRA; and (3) Cl(-)
      might increase blood pressure and PRA by further constricting the renal afferent
      arteriole.

PMID- 11231363
TI  - Mass spectrometry proves under-O-glycosylation of glomerular IgA1 in IgA
      nephropathy.
AB  - BACKGROUND: The IgA1 molecule, which is predominantly deposited in glomeruli in
      IgA nephropathy (IgAN), is a unique serum glycoprotein because it has O-glycan
      side chains in its hinge region. Our study was conducted to investigate the O
      glycan structure in the glomerular IgA1 in IgAN. METHODS: The IgA1 was separated
      from 290 renal biopsy specimens of 278 IgAN patients and from four serum IgA1
      samples (IgAN, 2; control, 2). The variety of O-glycan glycoform was determined
      by estimating the precise molecular weights of the IgA1 hinge glycopeptides using
      matrix-assisted laser desorption ionization time of flight mass spectrometry.
      RESULTS: The peak distribution of IgA1 hinge glycopeptides clearly shifted to
      lesser molecular weights in both glomerular and serum IgA1 in IgAN compared with
      the serum IgA1 of controls. In the five major peaks of IgA1 hinge glycopeptides
      in each sample, the numbers of carbohydrates composing O-glycans (GalNAc, Gal,
      and NANA) in the deposited and serum IgA1 in IgAN patients were significantly
      fewer than those in the serum IgA1 in the control groups. CONCLUSION: The O
      glycan side chains in the hinge of the glomerular IgA1 were highly
      underglycosylated in IgAN. These results indicate that the decreased sialylation
      and galactosylation of the IgA1 hinge glycopeptides play a crucial role in its
      glomerular deposition in IgAN.

PMID- 11231364
TI  - Bone mineral density and histology in distal renal tubular acidosis.
AB  - BACKGROUND: Chronic metabolic acidosis in distal renal tubular acidosis (RTA) has
      been implicated in the pathogenesis of enhanced bone resorption and osteopenia,
      resulting in a loss of bone mineral content. However, histomorphometric and bone
      densitometric studies of patients who suffered from long-standing distal RTA have
      rarely been done. METHODS: A cross-sectional study to determine the alterations
      of bone mineral density (BMD) and histology was done in 14 nonazotemic RTA
      patients (11 females and 3 males) who had never received alkaline therapy before
      enrolling into this study. The mean age was 32.7 +/- 11.9 years. BMD measurements
      and transiliac bone biopsy were done in all patients. Blood chemistries, intact
      parathyroid hormone level, and a 24-hour urine collection for the determination
      of urinary calcium, phosphate, sodium, and potassium were obtained from the RTA
      patients at the time of bone biopsy. Data from 28 age-, sex-, and body mass index
      matched, normal controls who were residents in the same area were also obtained.
      RESULTS: Urinary excretion of calcium was 2.05 +/- 1.59 mmol/day. No patient had
      hypercalciuria. The serum intact parathyroid hormone level was 15.92 +/- 8.48
      pg/mL. RTA patients had lower BMD in most areas when compared with normal
      controls. There were two patients who suffered from a pathologic fracture at the
      femur. Bone histomorphometry from RTA patients shows a significantly decreased
      bone formation rate (0.02 +/- 0.02 vs. 0.07 +/- 0.045 microm(3)/microm(2)/day, P
      < 0.05), not significantly decreased osteoblastic surface (0.78 +/- 1.03% vs. 2.6
      +/- 1.1%) and osteoclastic surface (0.05 +/- 0.03 vs. 0.13 +/- 0.23%), but
      significantly increased osteoid surface (31.47 +/- 24.52 vs. 5.79 +/- 4.39%, P <
      0.05) and osteoid volume (2.95 +/- 3.09 vs. 0.92 +/- 1.05%, P < 0.05) when
      compared with those of normal controls. There was no difference in osteoid
      thickness (10.65 +/- 6.10 vs. 8.69 +/- 2.14 microm). Only one distal RTA patient
      who had a marked increase in osteoid thickness justified the diagnosis of
      osteomalacia. CONCLUSIONS: This study demonstrates that low bone mass is common
      in distal RTA patients. Chronic metabolic acidosis results in suppression of bone
      formation and resorption, which in turn may contribute to the development of low
      bone mass in distal RTA patients. Although minor elevations in osteoid surface
      and osteoid volume are found among distal RTA patients, overt osteomalacia is not
      the predominant bone lesion.

PMID- 11231365
TI  - Tubular stress test detects subclinical reduction in renal functioning mass.
AB  - BACKGROUND: To develop a test that would disclose subclinical impairment in renal
      function, we studied the increment in tubular secretion of creatinine (TS(Cr))
      induced by intravenous creatinine administration. METHODS: Studies were done in
      14 normal individuals, 7 kidney donors (KDs), and 11 transplant recipients (Tx),
      all of whom had normal creatinine levels (P(Cr) <133 micromol/L). Creatinine
      infusion studies determined that maximal stimulation of TS(Cr) resulted from
      P(Cr) levels of 500 to 700 micromol/L. Therefore, in the tubular stress test,
      clearances, urinary excretion of creatinine (U(Cr)V) and TS(Cr) were determined
      before and after (15 to 105 min) a single bolus injection of 88.4 mmol/kg body
      wt, which resulted in the target P(Cr) levels. RESULTS: Baseline determinations
      of P(Cr), U(Cr)V, and TS(Cr) were not significantly different in the study
      groups. Stimulated U(Cr)V (nmol/kg/min) was higher in normals (426 +/- 82) than
      in KDs (338 +/- 72, P < 0.05) and Tx patients (311 +/- 66, P < 0.01). Similarly,
      TS(Cr) (nmol/kg/min) was higher (P < 0.001) in normals (180 +/- 60) than in KDs
      (155 +/- 54) and Tx patients (86 +/- 35). Furthermore, the transplanted kidney
      responded worse than the solitary normal kidney (P < 0.05), despite having
      similar levels of glomerular filtration rate (GFR). The tubular stress test
      increased TS(Cr) 11.3 +/- 6.2 times in normals, 4.3 +/- 1.2 times in KDs (P <
      0.01), and 2.5 times in Tx (P < 0.001). CONCLUSIONS: Impaired tubular secretory
      response to a creatinine load is a more sensitive index of reduced functioning
      renal mass than levels of P(Cr) and GFR. The tubular stress test may be useful in
      following the natural history of kidney disease and the results of therapeutic
      interventions.

PMID- 11231366
TI  - Oral vitamin B(12) and high-dose folic acid in hemodialysis patients with hyper
      homocyst(e)inemia.
AB  - BACKGROUND: Hyper-homocyst(e)inemia is an independent risk factor for
      atherosclerotic vascular disease in patients with end-stage renal disease (ESRD),
      although optimal treatment remains unknown. This randomized, double-blind,
      placebo-controlled study was designed to measure the effect of high-dose oral
      vitamin B(12) and folic acid on predialysis total homocyst(e)ine levels in
      patients with ESRD. METHODS: We studied 81 hemodialysis patients who had hyper
      homocyst(e)inemia (>16 micromol/L) on varied doses of a multivitamin containing 1
      mg of folic acid/day. After screening blood work, all patients were switched to
      daily multivitamin therapy, including 1 mg of folic acid for four weeks. For all
      patients, vitamin B(12), 1 mg/day, was added for an additional four weeks.
      Patients were then randomized to receive four weeks of 0, 5, or 20 mg of folic
      acid in addition to the multivitamin and vitamin B(12) (all given daily).
      RESULTS: Screening homocyst(e)ine levels (mean 27.7 micromol/L) decreased by
      19.2% after four weeks of treatment with a daily multivitamin containing 1 mg of
      folic acid (P < 0.001). Homocyst(e)ine levels were reduced further from 22.3 to
      18.6 micromol/L (mean reduction 16.7%, 95% CI 11.8 to 21.6%, P < 0.001) after
      four weeks of therapy with vitamin B(12) (1 mg/day). There was no significant
      difference in mean reduction of homocyst(e)ine levels after therapy with high
      dose folic acid compared with placebo (P = 0.35). CONCLUSIONS: The optimal oral
      treatment of hyper-homocyst(e)inemia in hemodialysis patients consists of 1 mg of
      folic acid and 1 mg of oral vitamin B(12) daily. Whether this treatment will
      lower the risk of future atherosclerotic vascular events remains to be
      investigated.

PMID- 11231367
TI  - Birth weight and risk of renal cell cancer.
AB  - BACKGROUND: The prenatal period has been suggested to be important for future
      cancer risk. Conditions in utero are also important for the development of the
      kidney, and birth weight, a marker of fetal nutrition and growth, is linearly
      correlated with the number of nephrons and the structural and functional unit of
      the kidney. An association between birth weight and renal cell cancer, the major
      form of kidney cancer, is biologically plausible, but has never been studied.
      METHODS: We conducted a population-based, case-controlled study in Sweden of men
      and women aged 20 to 79 years. We collected self-reported information on
      categories of birth weight from 648 patients with newly diagnosed renal cell
      cancer and from 900 frequency-matched control subjects. We used unconditional
      logistic regression to calculate odds ratios (ORs) and 95% confidence intervals
      (CIs) as estimates of the relative risks. RESULTS: An increased risk of renal
      cell cancer was observed among men with a birth weight of > or =3500 g (adjusted
      OR = 1.3, 95% CI, 1.0 to 1.8) compared with men with a birth weight between 3000
      and 3499 g, especially in the subgroup without hypertension or diabetes (adjusted
      OR = 1.8, 95% CI, 1.2 to 2.6). No clear association among men with a birth weight
      <3000 g or among women was found. CONCLUSIONS: Our study shows that conditions in
      utero, reflected by birth weight, might affect the risk of renal cell cancer in
      adulthood. It is unclear why no association was found among women. Further
      studies, based on weight from birth certificates, are needed to clarify this
      relationship.

PMID- 11231368
TI  - Leptin is a negative acute phase protein in chronic hemodialysis patients.
AB  - BACKGROUND: Hypoalbuminemia strongly predicts death in hemodialysis patients and
      results from both inflammation and malnutrition. One potential link between
      malnutrition and inflammation is appetite suppression triggered by inflammation.
      Leptin is secreted by adipose tissue and suppresses appetite, and it is also a
      positive acute phase protein in the rat. Factored for body weight, leptin is
      known to be increased in hemodialysis patients, but its relationship to
      inflammation is unknown. METHODS: We examined the relationship between
      spontaneously occurring activation of the acute phase response and leptin levels
      in 29 chronic hemodialysis patients. Serum samples were obtained three times
      weekly for six weeks and then monthly from 29 chronic hemodialysis patients, and
      the levels of the positive acute phase proteins [C-reactive protein (CRP), alpha1
      acid glycoprotein (alpha1 AG), serum amyloid A, ceruloplasmin] and the negative
      acute phase proteins (albumin and transferrin) as well as leptin and interleukin
      6 (IL-6) were measured. RESULTS: Positive and negative acute phase proteins were
      evaluated at the maximum CRP (mean, 9.42 +/- 1.14 mg/dL) and minimum values
      (mean, 0.41 +/- 0.09 mg/dL). When CRP was elevated, leptin levels were
      significantly reduced, as were the negative acute phase proteins albumin and
      transferrin. Serum amyloid A, ceruloplasmin, alpha1 acid glycoprotein, and IL-6
      were all significantly increased at the maximum CRP level, compatible with
      general activation of the acute phase response. The change in leptin correlated
      negatively with the change in CRP (R = 0.437, P = 0.018), as did changes in
      albumin (R = 0.620, P < 0.001). CONCLUSIONS: Leptin is not increased as a
      consequence of inflammation in hemodialysis patients, but behaves as a negative
      rather than as a positive acute phase protein. Inflammation is unlikely to reduce
      appetite in dialysis patients through a leptin-mediated mechanism.

PMID- 11231369
TI  - Validation of questionnaires to estimate physical activity and functioning in end
      stage renal disease.
AB  - BACKGROUND: Patients on dialysis are less physically active than sedentary
      persons with normal kidney function. To assess the consequences of inactivity and
      the results of efforts to increase activity in the end-stage renal disease (ESRD)
      population, valid instruments to measure physical activity and physical
      functioning in this group are needed. METHODS: We performed a cross-sectional
      study to establish the validity in ESRD of several questionnaires designed to
      measure physical activity or physical functioning in the general population.
      Questionnaires studied included the Stanford 7-day Physical Activity Recall
      questionnaire (PAR), the Physical Activity Scale for the Elderly (PASE), the
      Human Activity Profile (HAP), and the Medical Outcomes Study Short Form 36-item
      questionnaire (SF-36). Physical activity was measured using three-dimensional
      activity monitors (accelerometers) over a seven-day period (the "gold standard").
      Patients also underwent physical performance tests, including measurement of gait
      speed, stair climbing time, and chair rising time. Study questionnaires were
      administered, and questionnaire results were compared with each other and with
      activity monitor and physical performance test results. RESULTS: Thirty-nine
      maintenance hemodialysis patients participated in the study. Dialysis patients
      scored worse than previously published healthy norms on all tests. All
      questionnaires correlated with seven-day accelerometry and with at least one
      measure of physical performance. The HAP correlated best with accelerometry (r =
      0.78, P < 0.0001). Seventy-five percent of the variability in physical activity
      measured by accelerometry could be explained by a model that combined information
      from the HAP and the PASE. The HAP and the physical functioning scale of the SF
      36 were about equally well correlated with physical performance measures.
      CONCLUSIONS: These questionnaires are valid in patients on hemodialysis and
      should be used to study the physical activity and rehabilitation efforts in this
      population further.

PMID- 11231370
TI  - Role of diuretics in the preservation of residual renal function in patients on
      continuous ambulatory peritoneal dialysis.
AB  - BACKGROUND: Patients on continuous ambulatory peritoneal dialysis (CAPD) are
      dependent on residual renal function for solute and water clearances, and this
      declines with time on dialysis. Loop diuretics have been postulated to slow this
      decline. METHODS: Sixty-one patients new to dialysis were randomly assigned to
      either furosemide 250 mg every day or no furosemide at the time of CAPD training
      and were followed prospectively. Urine volume (UV), urea clearance (C(Urea)), and
      creatinine clearance on cimetidine (C(Cr)) were measured at randomization at six
      months and at one year. Patients underwent a standard four-hour peritoneum
      equilibrium test, and total body water was measured by bioelectrical impedance.
      Results were expressed on an intention-to-treat basis. RESULTS: UV, C(Cr), and
      C(Urea) were similar at randomization (1020 +/- 104 vs. 1040 +/- 130 mL/24 hours,
      4.95 +/- 0.51 vs. 4.07 +/- 0.40 mL/min/1.73 m2, 0.91 +/- 0.09 vs. 0.84 +/- 0.08,
      diuretic vs. control). UV in the diuretic-treated group increased, whereas in the
      control group, it declined (+176 vs. -200 mL/24 hours at 6 months and +48.8 vs. 
      305 mL/24 hours at 1 year, P < 0.05). C(Cr) and C(Urea) declined at a constant
      rate and were unaffected by diuretic administration (0.12 +/- 0.05 vs. 0.071 +/-
      0.04 mL/min/1.73 m2/month, 0.020 +/- 0.01 vs. 0.019 +/- 0.01 per month). Urinary
      sodium excretion increased in the diuretic group and declined in the control
      group (+0.72 +/- 0.85 vs. -2.56 +/- 1.31 mmol/24 hours/month, P = 0.04). Body
      weight rose in both groups (4.3 vs. 3.0 kg), but the percentage of total body
      weight rose in the control group and remained constant in the diuretic group (52
      +/- 2.4 vs. 64 +/- 6.6%, P = 0.10). CONCLUSIONS: Long-term furosemide produces a
      significant increase in UV over 12 months when on CAPD and may result in
      clinically significant improvement in fluid balance. However, furosemide has no
      effect on preserving residual renal function.

PMID- 11231371
TI  - Increased vascular growth in hemodialysis patients induced by platelet-derived
      diadenosine polyphosphates.
AB  - BACKGROUND: Enhanced vascular smooth muscle cell (VSMC) growth is one hallmark of
      atherosclerosis. One mechanism responsible for stimulating arterial smooth muscle
      cell growth is the release of growth factors from platelets aggregating at
      endothelial lesions. Since in end-stage renal failure (ESRF) atherogenesis is
      markedly accelerated, the release of VSMC growth factors on aggregation of
      platelets from hemodialysis patients, ESRF patients in the predialysis stage, and
      healthy subjects was examined. METHODS: Platelets were activated by thrombin, and
      the supernatant was tested for growth stimulation in VSMCs from rat aorta. The
      cell proliferation rate was determined by [(3)H]-thymidine incorporation in
      VSMCs. The diadenosine polyphosphate (Ap(n)A with N = 3 to 6) content in the
      supernatant and in intact platelets was determined using a chromatographic assay
      established on the basis of affinity- and reversed-phase chromatographic methods.
      RESULTS: The thrombin-activated platelet supernatant from hemodialysis patients
      (N = 15) increased the [(3)H]-thymidine incorporation rate in VSMC s in
      comparison to the supernatant of healthy control subjects (N = 17,
      counts/supernatant of 10(6) stimulated platelets +/- SEM, 604 +/- 71 vs. 364 +/-
      45, P < 0.05). The addition of the selective P2-receptor blocker pyridoxal
      phosphate-6-azophenyl-2,4-disulfonic acid to supernatants inhibited the
      stimulatory effects of Ap(n)A on the growth of vascular smooth muscle cells (219
      +/- 53 vs. 156 +/- 71 counts/supernatant of 106 stimulated platelets +/- SEM).
      The Ap(n)A (N = 3 to 6) amount of thrombin-activated platelet supernatants from
      hemodialysis patients was significantly higher than in platelets from 10 healthy
      control subjects (Ap(3)A, 119 +/- 32 vs. 12 +/- 3; Ap(4)A, 154 +/- 59 vs. 43 +/-
      20; Ap(5)A, 39 +/- 14 vs. 13 +/- 6; Ap(6)A, 42 +/- 19 vs. 2 +/- 1 fg/platelet +/-
      SEM, each P < 0.05, N = 10). The intracellular Ap(n)A (N = 3 to 6) amount of
      intact platelets from hemodialysis patients (N = 61) was significantly higher
      than that from healthy control subjects [N = 30, Ap(n)A amount (fg/platelet +/-
      SEM): Ap(3)A, 366 +/- 68 vs. 14.7 +/- 1; Ap(4)A, 336 +/- 48 vs. 19 +/- 2; Ap(5)A,
      227 +/- 35 vs. 10 +/- 1; Ap(6)A, 141 +/- 45 vs. 4 +/- 1; each P < 0.01].
      CONCLUSIONS: The increased amount of dinucleoside polyphosphate in platelets from
      hemodialysis patients may be an important additional atherogenic factor.

PMID- 11231372
TI  - Cold ischemia augments allogeneic-mediated injury in rat kidney allografts.
AB  - BACKGROUND: Some clinical studies demonstrate that kidney grafts with prolonged
      cold ischemia experience early acute rejection more often than those with minimal
      ischemia. The mechanism, however, is putative. Therefore, the aim of this study
      was to unravel the impact of ischemia on the immune response in rat kidney
      allografts compared with that in isografts. METHODS: To induce ischemic injury,
      donor kidneys were preserved for 24 hours in 4 degrees C University of Wisconsin
      solution before transplantation. No immunosuppression was administered. The
      histomorphology according to the BANFF criteria for acute rejection and
      infiltrating cells were assessed at days 1, 2, 3, 4, 6, and 8 post
      transplantation. RESULTS: In allografts, exposure of the kidney to ischemia led
      to a significantly earlier onset of interstitial cell infiltration and tubulitis
      compared with nonischemic allografts. The BANFF score of interstitial cell
      infiltration was 1 +/- 0 vs. 0.25 +/- 0.29 at day 3 and 2 +/- 0 vs. 1.25 +/- 0.25
      at day 4. In contrast, in isografts, the effect of ischemia on the histology was
      not significant. From day 6, the histologic differences between ischemic and
      nonischemic grafts disappeared. Ischemia led to a more intense expression of P
      selectin (day 1), intercellular adhesion molecule-1 (ICAM-1; day 2), and major
      histocompatibility complex (MHC) class II on endothelium and proximal tubular
      cells (day 2) in both allografts and isografts. Concurrently with the up
      regulated ICAM-1 and MHC expression, significantly more CD4(+) cells and
      macrophages infiltrated the ischemic allografts at days 2 and 3 and the ischemic
      isografts at day 4. Importantly, the influx of these cells after ischemia was
      significantly greater in allografts than in isografts. CONCLUSIONS: Cold ischemia
      augments allogeneic-mediated cell infiltration in rat kidney allografts. The
      earlier onset of acute rejection in 24-hour cold preserved allografts may be
      prevented by better preservation or treatment using tailored immunosuppression.

PMID- 11231373
TI  - Increased dietary salt accelerates chronic allograft nephropathy in rats.
AB  - BACKGROUND: Chronic allograft nephropathy (CAN), a major problem in renal
      transplantation, is related to both alloantigen-dependent and -independent
      processes. Because dietary salt intake modulated glomerular production of
      transforming growth factor-beta, which has been shown to play an important role
      in CAN, we hypothesized that dietary salt would directly enhance renal injury in
      a rodent model of CAN. METHODS: Dietary NaCl was increased from 1.0% (normal) to
      8.0% in a group of Fisher/Lewis rats 25 days following orthotopic renal
      transplantation and was continued until 16 weeks after transplantation. RESULTS:
      Blood pressure, which was recorded using radiotelemetry in the first eight-weeks
      post-transplantation, did not differ between the groups, but allograft recipients
      on the 8.0% NaCl diet rapidly demonstrated increased urinary albumin excretion.
      Renal function determined by dynamic functional imaging was worse in allograft
      recipients on the 8.0% NaCl diet by six weeks following transplantation.
      Histologic examination at 16 weeks confirmed a significant increase in allograft
      damage in the 8.0% NaCl group compared with allografts from rats on 1.0% NaCl
      diet. These findings included glomerulosclerosis and tubulointerstitial injury
      that consisted of fibrosis, tubular atrophy and dilation, intratubular casts, and
      tubular epithelial cell damage. Small arteries and arterioles did not show
      evidence of damage from hypertension or other abnormality. CONCLUSIONS: In this
      model of CAN, renal allograft dysfunction preceded hypertension and was
      accelerated significantly by an increase in dietary salt.

PMID- 11231374
TI  - Elevated blood pressure predicts the risk of acute rejection in renal allograft
      recipients.
AB  - BACKGROUND: Acute rejection (AR) is a strong predictor of renal allograft
      survival. Recent advances in immunosuppression have reduced considerably the
      incidence of AR. Still, approximately 25% of patients have AR early post
      transplant, and the factors that predispose to AR have not been fully clarified.
      METHODS: The study includes 1641 adults, recipients of first cadaveric (CAD, N =
      1195) or living related renal grafts (LRD, N = 446), transplanted in one
      institution. The variables associated with the occurrence of AR during the first
      year post-transplant were identified. RESULTS: By univariate analyses, AR was
      associated with the following variables: younger (P < 0.001); heavier (P =
      0.003); and African American recipients (P = 0.002); CAD transplants (P = 0.001);
      higher number of HLA mismatches (P = 0.001); delayed graft function (DGF, P =
      0.001); higher levels of serum creatinine post-transplant (P = 0.003); and higher
      levels of systolic and/or diastolic blood pressure (BP) post-transplant (P <
      0.001). Higher BP levels were also associated with earlier AR episodes (P <
      0.0001). By multivariable analysis AR was significantly associated with recipient
      age, number of HLA mismatches, DGF, pre-PRA and systolic BP. Analysis of BP
      measured weekly post-transplant indicated that elevated BP levels, even three
      weeks prior to the AR episode, were significantly associated with AR. For every
      level of BP, the use of BP medications was associated with a lower incidence of
      AR (P < 0.0001). Furthermore, the use of calcium channel blockers was also
      associated with lower incidence of AR (P = 0.001). Of note, 81% of recipients
      whose BP increased after the transplant had AR. In contrast, 22% of patients
      whose BP declined post-transplant had AR. CONCLUSIONS: Elevated BP levels post
      transplant identify patients at high risk of AR independently of graft function.
      Treatment of BP and reduction of BP levels appears to be associated with a
      decreased risk of AR. We hypothesize that high BP may be an indicator of a
      particular type of allograft damage, perhaps ischemic, that may predispose to AR.

PMID- 11231375
TI  - Anthropometry-based equations overestimate the urea distribution volume in
      hemodialysis patients.
AB  - BACKGROUND: Protein intake in hemodialysis patients can be estimated indirectly
      from the protein equivalent of total nitrogen appearance (PNA) during the
      interdialytic period. A reliable estimate of the patient's urea distribution
      volume (UDV) is required to assess protein intake from PNA values. UDV values are
      derived frequently from simple anthropometric equations. METHODS: UDV values
      based on anthropometric methods were compared with UDV values determined by
      direct dialysate quantitation (DDQ) in 54 stable chronic hemodialysis patients.
      The anthropometric methods included the following: the Watson equations (WAT), a
      fixed proportion of postdialysis body weight, 58% for males and 55% for females
      (% body wt), and skinfold thickness measurements (SFT). Postdialysis blood
      samples were drawn at 15-minutes postdialysis. RESULTS: UDV(WAT) and UDV(SFT)
      overestimated UDV(DDQ) by about 8 L [limits of agreement (LOA): 2.6 to 14.2 L] in
      males and about 6 L (LOA: -0.8 to 12.4 L) in females. The overestimation by
      UDV(%BW) was even larger: 10.5 L (LOA: 2.0 to 19.0 L) in males and 11.1 L (LOA:
      2.1 to 20.1 L) in females. The difference between UDV(%BW) and UDV(DDQ)
      correlated with the percentage of body fat (r = 0.57) and body mass index (r =
      0.48). In a subgroup of seven patients, UDV was also determined by dilution (DIL)
      of the stable isotope [(13)C]urea. UDV(WAT) and UDV(%BW) overestimated UDV(DIL)
      significantly. In contrast, UDV(DDQ) was significantly smaller than UDV(DIL),
      even after correction for incomplete postdialysis equilibration. PNA values
      calculated using the various UDV estimates were compared with dietary protein
      intake (DPI) assessed from food records. PNA(DDQ) (61 +/- 10 g/day) did not
      differ significantly from DPI (63 +/- 13 g/day), but the agreement in individual
      patients varied considerably (LOA, -24 to 20 g/day). Anthropometric-based PNA
      values overestimated DPI by 8 to 16 g/day. CONCLUSIONS: Anthropometry-based
      equations overestimate UDV values in hemodialysis patients, leading to an
      overestimation of PNA values. Although PNA measurements by DDQ appear to be more
      reliable for assessing protein intake, PNA(DDQ) values should be interpreted with
      caution in individual hemodialysis patients.

PMID- 11231376
TI  - Preventing dialysis hypotension: a comparison of usual protective maneuvers.
AB  - BACKGROUND: Intradialytic hypotension (IH) is a common adverse event. Currently,
      there are several commonly utilized therapies of IH, but they have not been
      compared directly in the same group of patients. We performed the present study
      in order to learn which of these techniques is most effective so that a rational
      approach to treating IH could then be formulated. METHODS: A single-blinded,
      crossover study design of five different protocols was undertaken in 10
      hemodialysis patients with a prior history of IH. Each patient first underwent
      one week (three dialyses) of standard dialysis (dialysate sodium 138 mEq/L). Then
      each patient was subjected to one week each (three dialyses) of the four test
      protocols, performed in random order in a blinded fashion. The specific protocols
      were as follows: high sodium dialysate, in which the patient was dialyzed using a
      dialysate sodium of 144 mEq/L; sodium modeling, during which the dialysate sodium
      declined from 152 to 140 mEq/L in the last half hour of dialysis; one hour of
      isolated ultrafiltration followed by three hours of isovolemic dialysis; and cool
      temperature dialysis in which the dialysate was cooled to 35 degrees C. RESULTS:
      Weight loss in each of the five protocols was essentially identical, varying
      between 2.9 and 3 kg. There were significantly fewer hypotensive episodes per
      treatment in the sodium modeling, high sodium, and cool temperature protocols as
      compared with the standard protocol (P < 0.05). Ultrafiltration followed by
      dialysis was associated with a significantly greater number of hypotensive
      episodes per treatment than any of the three test protocols (P < 0.05).
      Similarly, the number of nursing interventions required for IH per treatment was
      significantly greater in the standard dialysis and in the isolated
      ultrafiltration protocols compared with sodium modeling and cool temperature
      protocols (P < 0.05). The number of hypotensive signs and symptoms per treatment
      was also significantly reduced during the sodium modeling and cool temperature
      protocols compared with the standard protocol (P < 0.004 and P < 0.02,
      respectively). Again, the isolated ultrafiltration protocol resulted in
      significantly more hypotensive symptoms and signs than the three test protocols
      (P < 0.005). Finally, the nadir mean arterial pressures were significantly lower
      in the standard and isolated ultrafiltration protocols when compared with the
      three test protocols (P < 0.05). The upright postdialysis blood pressure was best
      preserved in the sodium modeling and cool temperature protocols compared with the
      standard and isolated ultrafiltration protocols (P < 0.05). CONCLUSION: This
      study supports the use of sodium modeling as a first step in combating IH. Also
      effective were the use of cool-temperature dialysate and a high-sodium dialysate.
      All three test protocols were well tolerated. As applied in this study, isolated
      ultrafiltration followed by isovolemic dialysis was notably less effective in
      reducing IH.

PMID- 11231377
TI  - Parathyroid gland hyperplasia in uremia.

PMID- 11231378
TI  - Relaxin and renal fibrosis.

PMID- 11231379
TI  - Albuminuria in patients with type II diabetes with retinopathy.

PMID- 11231381
TI  - Recent developments in the management of secondary hyperparathyroidism.

PMID- 11231382
TI  - Maldigestion and malabsorption.

PMID- 11231383
TI  - Factors associated with acceptance and full publication of GI endoscopic research
      originally published in abstract form.
AB  - BACKGROUND: Many abstracts submitted to annual scientific meetings never come to
      full publication in peer-reviewed journals. The objective of this study was to
      determine factors associated with the fate of endoscopic research abstracts
      submitted to the annual scientific meeting of the American Society for
      Gastrointestinal Endoscopy (ASGE). METHODS: All abstracts (n = 461) submitted to
      the annual meeting of the ASGE in May of 1994 were retrospectively reviewed. The
      following databases were searched for evidence of publication of abstracts in
      full-manuscript form: Medline, HealthSTAR, Current Contents, CINHAL, and
      Cancerlit. All abstracts were reviewed between May 4, 1998 and June 30, 1998.
      Univariate and multivariate analysis were performed to determine the association
      between abstract characteristics and acceptance for presentation at the meeting
      and for publication. RESULTS: Fifty-five percent (247/451) of submitted abstracts
      were accepted for presentation. In univariate analysis, pediatric studies,
      prospective studies, randomized studies, and studies from university-affiliated
      medical centers (UAMC), were more likely to be accepted for presentation (p <
      0.05). In multivariate analysis, the variables: pediatric studies (p = 0.01),
      prospective studies (p = 0.005), randomized studies (p = 0.06), and studies from
      UAMC (p = 0.01) predicted acceptance of abstracts for presentation at the
      meeting. The overall publication rate was 25.1%. The publication rates 1, 2, 3,
      and 4 years after the meeting were 6.7%, 16.2%, 22.8%, and 25.1%, respectively.
      Multivariate Cox proportional hazards analysis showed that accepted abstracts (p
      = 0.0003) studies reporting positive results (p = 0.0015), and studies from
      outside the United States (p = 0.036) were more likely to be published in
      manuscript form. CONCLUSIONS: The overall publication rate of abstracts reporting
      endoscopic research is 25%, lower than that in any published report from other
      medical societies. Abstracts from the United States were less likely to be
      published in full-manuscript form. Although there was no positive outcome bias
      for acceptance of abstracts for presentation at the meeting, there was bias
      toward publication of statistically significant results. Further investigations
      are warranted to determine the variation in the publication of research results
      according to country of origin and to determine factors that hinder publication
      of GI endoscopic research in manuscript form.

PMID- 11231384
TI  - Accuracy of provisional diagnoses of dyspepsia in patients undergoing first
      endoscopy.
AB  - BACKGROUND: This study assessed agreement between provisional and endoscopic
      diagnoses for patients with dyspepsia undergoing initial endoscopy, and examined
      variation between clinicians at 2 hospitals. METHODS: This was a retrospective
      review of 423 consecutive patients. RESULTS: Crude percentage agreement ranged
      from 55% to 97%. Kappa scores revealed poor agreement: peptic ulcers (0.11: 95%
      CI [0.05, 0.17]); gastroesophageal reflux disease (0.29: 95% CI [0.20, 0.38]);
      benign esophageal stricture (0.33: 95% CI [0.08, 0.58]); and cancer (0.12: 95% CI
      [-0.12, 0.36]). Positive and negative predictive values for cancer and benign
      esophageal stricture showed that agreement for a negative diagnosis was almost
      perfect, whereas agreement for a positive diagnosis was low. Only 17% of patients
      with cancer were given an accurate provisional diagnosis. Accuracy of diagnosis
      did not vary substantially between hospitals. CONCLUSIONS: Crude percentage
      agreement is misleading. Emphasis should be placed on better prediction of
      cancer, benign esophageal stricture, and peptic ulcer disease. Accuracy of
      provisional diagnosis in everyday practice is no worse than that found in
      prospective studies in which clinicians knew a priori that diagnoses would be
      scrutinized. The difficulty of predicting diagnoses supports increased reliance
      on endoscopy.

PMID- 11231385
TI  - The comparison of midazolam and topical lidocaine spray versus the combination of
      midazolam, meperidine, and topical lidocaine spray to sedate patients for upper
      endoscopy.
AB  - BACKGROUND: Whether an opiate-benzodiazepine combination is superior to
      benzodiazepine alone for sedation in upper endoscopy is controversial. The
      purpose of this study was to compare the effectiveness of intravenous midazolam
      alone versus the combination of intravenous midazolam and intravenous meperidine
      for the sedation of patients undergoing upper endoscopy. METHODS: One hundred
      seven patients scheduled for outpatient diagnostic esophagogastroduodenoscopy
      were randomly assigned to receive 50 mg intravenous meperidine (53 of 107) or
      placebo (54 of 107). All patients received topical lidocaine spray and as much
      midazolam as the endoscopist thought the patient needed. Patients and
      endoscopists were blinded as to assignment. Data collected included intubation
      time (seconds), procedure time (minutes), pulse, blood pressure, complications,
      and the need for reversal agents. The endoscopist evaluated the quality of
      sedation immediately after the procedure (1 = excellent, 2 = good, 3 = fair, and
      4 = poor). The patient evaluated the procedure the next day by phone (1 = no
      discomfort or did not remember, 2 = slightly uncomfortable, 3 = extremely
      uncomfortable, and 4 = unacceptable). Patients were also asked whether they would
      agree to another esophagogastroduodenoscopy if their doctor thought it was
      medically necessary. RESULTS: The intubation time, procedure time and blood
      pressure were not significantly different between the 2 groups. In comparing the
      meperidine group versus placebo group, the highest pulse (82.3 vs. 93.7, p =
      0.0010), lowest pulse (67.2 vs. 72.3, p = 0.0194) and amount of midazolam used
      (4.0 vs. 4.8 mg, p = 0.0185 or 0.53 vs. 0.67 mg/kg, p = 0.0083) were
      significantly different by using a t test analysis. Patient evaluations comparing
      meperidine versus placebo showed responses of 1 (52 vs. 49), 2 (1 vs. 3), 3 (0
      vs. 2) and 4 (0 vs. 0), which were not significantly different. The
      endoscopists'evaluation comparing meperidine versus placebo gave responses of
      excellent (44 vs. 27), good (6 vs. 22), fair (3 vs. 5) and poor (0 vs. 0), which
      were highly significantly different (p < 0.001) by using chi-square statistical
      techniques. CONCLUSION: The addition of meperidine to midazolam in sedating
      patients undergoing upper endoscopy adds no benefit from the patient viewpoint,
      whereas endoscopists favored the use of both medications.

PMID- 11231386
TI  - The reliability of EUS for the diagnosis of chronic pancreatitis: interobserver
      agreement among experienced endosonographers.
AB  - BACKGROUND: Endoscopic ultrasound (EUS) is a minimally invasive, low risk method
      of diagnosis for chronic pancreatitis (CP). The degree to which endosonographers
      agree on the features and diagnosis of CP is unknown. For EUS to be considered an
      accurate test for CP, there must be good interobserver agreement. METHODS: Forty
      five pancreatic EUS examinations were videotaped by 3 experienced
      endosonographers. Examinations from 33 patients with suspected CP based on
      typical symptoms, as well as 12 control patients without suspected CP, were
      included. Eleven experienced endosonographers ("experts") who were blinded to
      clinical information independently evaluated all videotaped examinations for the
      presence of CP and the following 9 validated features of CP: echogenic foci,
      strands, lobularity, cysts, stones, duct dilatation, duct irregularity,
      hyperechoic duct margins, and visible side branches. The experts also ranked
      (most to least) which features they believed to be the most indicative of CP.
      Interobserver agreement was expressed as the kappa (kappa) statistic. RESULTS:
      There was moderately good overall agreement for the final diagnosis of CP (kappa
      = 0.45). Agreement was good for individual features of duct dilatation (kappa =
      0.6) and lobularity (kappa = 0.51) but poor for the other 7 features (kappa <
      0.4). The expert panel had consensus or near consensus agreement (greater than
      90%) on 206 of 450 (46%) individual EUS features including 22 of 45 diagnoses of
      CP. Agreement on the final diagnosis of CP was moderately good for those trained
      in third tier fellowships (kappa = 0.42 +/- 0.03) and those with more than 1100
      lifetime pancreatic EUS examinations (kappa = 0.46 +/- 0.05). The presence of
      stones was regarded as the most predictive feature of CP by all endosonographers,
      followed by visible side branches, cysts, lobularity, irregular main pancreatic
      duct, hyperechoic foci, hyperechoic strands, main pancreatic duct dilatation, and
      main duct hyperechoic margins. The most common diagnostic criterion for the
      diagnosis of CP was the total number of features (median 4 or greater, range 3 or
      greater to 5 or greater). CONCLUSIONS: EUS is a reliable method for the diagnosis
      of chronic pancreatitis with good interobserver agreement among experienced
      endosonographers. Agreement on the EUS diagnosis of chronic pancreatitis is
      comparable to other commonly used endoscopic procedures such as bleeding ulcer
      stigmata and computed tomography of the brain for stroke localization and better
      than the physical diagnosis of heart sounds.

PMID- 11231388
TI  - Impact of endoscopic therapy on the survival of patients with primary sclerosing
      cholangitis.
AB  - BACKGROUND: Endoscopic measures such as balloon dilation can relieve obstruction
      and improve symptoms in patients with primary sclerosing cholangitis (PSC).
      However, the influence of repeated endoscopy to maintain biliary patency on the
      survival of patients with PSC is unclear. METHODS: This study evaluated the
      impact of endoscopic therapy on the survival of consecutive patients with PSC
      undergoing endoscopic therapy. During a 6-year period 63 patients underwent
      endoscopic therapy. After initial therapy, patients were followed for a median of
      34 months. Endoscopic therapy primarily consisted of repeated balloon dilation of
      dominant biliary strictures. The observed survival of this cohort was estimated
      (Kaplan-Meier). The predicted survival of the cohort was estimated by using the
      Mayo Clinic survival model based on clinical information obtained within 3 months
      before first endoscopic therapy. The Mayo Risk Score was calculated by using the
      equation R = (0.03 Age, years) + (0.54 log(e) Bilirubin mg/dL) + (0.54 log(e)
      Aspartate aminotransferase U/mL) + (1.24 Bleed history) - (0.84 Albumin gm/dL).
      RESULTS: The observed survival over 5 years was significantly higher than the
      predicted 5-year survival (83% vs. 65%, respectively; p = 0.027). CONCLUSION:
      These data suggest that repeated endoscopic attempts to maintain biliary patency
      may improve the survival of patients with PSC and dominant strictures.

PMID- 11231387
TI  - Transpapillary intraductal US prior to biliary drainage in the assessment of
      longitudinal spread of extrahepatic bile duct carcinoma.
AB  - BACKGROUND: The utility of intraductal US via the transpapillary route prior to
      biliary drainage in the assessment of longitudinal extension of extrahepatic bile
      duct carcinoma was investigated. METHODS: In 19 patients with extrahepatic bile
      duct carcinoma who underwent surgical resection, an ultrasonic probe (diameter,
      2.0 mm; frequency, 20 MHz) was inserted into the bile duct via the transpapillary
      route prior to biliary drainage. Longitudinal cancer extension along the bile
      duct was prospectively determined and compared with the histologic findings in
      the resected specimens. RESULTS: Results on the hepatic side were as follows:
      Intraductal US demonstrated more extensive longitudinal cancer spread than
      cholangiography in 9 of 19 patients with one instance of overdiagnosis. The
      accuracy of intraductal US in assessing the extent of spread (84%) was superior
      to that of cholangiography (47%) (p < 0.05). Results on the duodenal side were as
      follows: In patients with suprapancreatic bile duct cancer (n = 14), intraductal
      US demonstrated more extensive longitudinal cancer spread than cholangiography in
      8 of 14 patients. The accuracy of intraductal US in assessing the extent of the
      spread (86%) was superior to that of cholangiography (43%) (p < 0.05).
      CONCLUSIONS: Transpapillary intraductal US prior to biliary drainage is useful in
      demonstrating longitudinal extension of bile duct cancer. However, the surgical
      margins were inaccurate in some patients.

PMID- 11231389
TI  - Is peripapillary choledochoduodenal fistula an indication for endoscopic
      sphincterotomy?
AB  - BACKGROUND: Most patients with a peripapillary choledochoduodenal fistula undergo
      fistulotomy by endoscopic sphincterotomy for the treatment of bile duct stones.
      However, whether sphincterotomy should be performed in patients with the fistula
      but without stones is controversial. METHODS: Among 165 patients in whom a benign
      peripapillary choledochoduodenal fistula was diagnosed at ERCP, the clinical
      outcome was retrospectively analyzed and compared between those who underwent
      fistulotomy by endoscopic sphincterotomy (group 1) and those whose fistula was
      left untreated (group 2). All patients with hepatolithiasis, residual stones,
      biliary diversion, or transduodenal papilloplasty were excluded (32, leaving
      133). Fistulas were divided into types I and II according to the location of the
      fistula (Ikeda classification). RESULTS: Follow-up data collected during a median
      period of 124 months were available for 127 of 133 patients (95%), 76 in group 1
      and 53 in group 2. Late complications were bile duct stone recurrence (17
      patients), acute cholangitis (7 patients), and biliary carcinoma (2 patients).
      The incidence of stone recurrence was not significantly different between the 2
      groups (p = 0.1). In group 2, 4 patients (8%) with an untreated type II fistula
      had 1 to 3 episodes of presumed reflux cholangitis, which resolved quickly with
      conservative treatment. CONCLUSIONS: Endoscopic sphincterotomy is not always
      necessary for peripapillary choledochoduodenal fistulas if bile duct stones are
      absent because reflux cholangitis is a relatively rare complication that can be
      easily managed.

PMID- 11231390
TI  - Percutaneous transhepatic cholangioscopic treatment for hepatolithiasis: an
      evaluation of long-term results and risk factors for recurrence.
AB  - BACKGROUND: Percutaneous transhepatic cholangioscopy (PTCS) has a major role in
      the treatment of hepatolithiasis. The aims of this study were to evaluate
      immediate and long-term results of PTCS treatment and to elucidate the risk
      factors for recurrence of stones or cholangitis. METHODS: A retrospective study
      was conducted of patients with hepatolithiasis who underwent PTCS treatment. A
      total of 92 patients underwent PTCS treatment and 68 were followed for 24 to 60
      months (median 42 months). RESULTS: Complete clearance of stones was achieved in
      74 (80%) patients. The rate of complete clearance was significantly lower in
      patients with severe intrahepatic strictures compared with that for those with no
      strictures (14 of 24, 58% vs. 16 of 16, 100%, p < 0.01) and those with mild to
      moderate strictures (14 of 24, 58% vs. 44 of 52, 85%, p < 0.05). Patients with
      severe intrahepatic strictures had a higher recurrence rate than those with no or
      mild strictures (100% vs. 28%, p < 0.01). In addition the recurrence rate in
      patients with advanced biliary cirrhosis (Child's class B or C) was higher than
      in those with no or mild (Child's class A) cirrhosis (89% vs. 29%, p < 0.01). In
      patients with type I and II hepatolithiasis (Tsunoda classification), stones
      recurred in 2 (12%) patients at 28 and 32 months after successful stone removal,
      without further recurrence afterwards. The recurrence rate in patients with type
      III and IV hepatolithiasis increased gradually up to 50% at 60 months of follow
      up. CONCLUSIONS: Severe intrahepatic stricture was the only factor that affected
      the immediate success rate of PTCS in the treatment of hepatolithiasis. Several
      risk factors including severe biliary stricture, advanced biliary cirrhosis and
      Tsunoda type III and IV affected the long-term results.

PMID- 11231391
TI  - Characterization of primary pure cholesterol hepatolithiasis: cholangioscopic and
      selective cholangiographic findings.
AB  - BACKGROUND: Primary pure cholesterol hepatolithiasis has been described recently.
      The aim of this study was to analyze its clinical and radiologic features,
      focusing on the cholangioscopic and selective cholangiographic findings. METHODS:
      Primary pure cholesterol hepatolithiasis was identified in 3% (6 of 172) of
      patients who were treated with cholangioscopic stone removal for primary
      hepatolithiasis during the study period from 1995 to 1999. These 6 consecutive
      patients (M/F 5:1, mean age 40 years) were enrolled in the study. They underwent
      abdominal US, CT, endoscopic retrograde cholangiography (ERC), and percutaneous
      transhepatic cholangioscopy (PTCS). After confirming that the stones were of the
      cholesterol type, cholangioscopic stone removal via the percutaneous transhepatic
      route was performed. For the prevention of recurrence, ursodeoxycholic acid (10
      mg/kg/day) was prescribed during follow-up. RESULTS: US demonstrated high
      echogenicity with strong shadowing in dilated peripheral ducts, whereas CT failed
      to demonstrate any intraductal abnormal density or calcification except localized
      duct dilatation. PTCS demonstrated multiple, white to yellowish stones that were
      morphologically readily distinguishable from brown pigment intrahepatic stones.
      In all patients, selective cholangiography disclosed the ductal abnormalities,
      which could not be delineated by ERC in 4 patients. Complete stone removal by
      PTCS was achieved in 5 of 6 patients. During follow-up (12 to 49 months, mean 22
      months), they were asymptomatic and stone recurrence was not detected by US.
      CONCLUSIONS: Primary pure cholesterol hepatolithiasis is distinguishable from the
      more common brown pigment hepatolithiasis by its cholangioscopic and selective
      cholangiographic characteristics.

PMID- 11231392
TI  - Clinical outcome of the use of enteral stents for palliation of patients with
      malignant upper GI obstruction.
AB  - BACKGROUND: The endoscopically placed enteral stent has emerged as a reasonable
      alternative to palliative surgery for malignant intestinal obstruction. This is a
      report of our experience with the use of enteral stents for nonesophageal
      malignant upper GI obstruction. METHODS: Data on all patients who had undergone
      enteral stent placement were reviewed. Those with a diagnosis of pancreatic
      cancer were compared with another similar cohort of patients who underwent
      palliative gastrojejunostomy. RESULTS: Thirty-one procedures were performed on 29
      patients (mean age 67.7 years). Thirteen (45%) were men and 16 (55%) women. The
      diagnoses were gastric (13.8%), duodenal (10.3%), pancreatic (41.4%), metastatic
      (27.6%), and other malignancies (6.9%). Malignant obstruction occurred at the
      pylorus (20.7%), first part of duodenum (37.9%), second part of duodenum (27.6%),
      third part of duodenum (3.5%), and anastomotic sites (10.3%). Twenty-nine (93.5%)
      procedures were successful and good clinical outcome was achieved in 25 (80.6%).
      Re-obstruction by tumor ingrowth occurred in 2 patients after a mean of 183 days.
      The median survival time for patients with pancreatic cancer who underwent
      enteral stent placement compared with those who underwent surgical
      gastrojejunostomy was 94 and 92 days, charges were $9921 and $28,173, and
      duration of hospitalization was 4 and 14 days, respectively (latter 2 differences
      with p value < 0.005). CONCLUSION: Endoscopic enteral stent placement of
      nonesophageal malignant upper GI obstruction is a safe, efficacious, and cost
      effective procedure with good clinical outcome, lower charges, and shorter
      hospitalization period than the surgical alternative.

PMID- 11231393
TI  - Methylene blue staining: is it really useful in Barrett's esophagus?
AB  - BACKGROUND: If areas of specialized intestinal metaplasia (SIM) or dysplasia in
      Barrett's esophagus can be identified at endoscopy, the number of biopsies could
      be reduced and the sensitivity of biopsy surveillance would increase. It has been
      suggested that methylene blue (MB) dye staining may be useful for this purpose.
      METHODS: Nine patients were prospectively studied with Barrett's esophagus.
      Staining involved sequential spraying of 10% N-acetylcysteine, 0.5% MB and water.
      Quadrantic biopsies were obtained from Barrett's epithelium and collected in
      separate containers depending on whether they were taken from stained or
      unstained areas. Seven patients undergoing yearly surveillance were asked to
      compare the discomfort of this endoscopy with that of previous surveillance
      endoscopies. Biopsies were analyzed for the presence and the percentage of SIM
      and dysplasia by a nonblinded pathologist. RESULTS: MB staining prolonged
      endoscopy by a mean of 8 minutes (47% increase in procedure time) and was
      associated with significant vomiting during the procedure in 2 patients. Staining
      was observed in all 9 patients. All 7 patients undergoing yearly endoscopic
      surveillance indicated more discomfort with endoscopy plus MB staining. Of 37
      biopsies from stained mucosa, 20 contained SIM; of 23 from unstained mucosa, 15
      contained SIM (57% sensitivity, 32% specificity for MB staining). CONCLUSIONS: In
      this small, nonblinded study MB staining was associated with prolongation of
      endoscopy, increased patient discomfort, and potentially serious complications
      and was neither very sensitive nor specific for SIM. It is our recommendation
      that this technique should not be routinely used in endoscopic surveillance of
      patients with Barrett's esophagus. Further studies of MB staining are needed.

PMID- 11231394
TI  - Single-step treatment of gallbladder and bile duct stones: a combined endoscopic
      laparoscopic technique.
AB  - BACKGROUND: The introduction of laparoscopic cholecystectomy has given rise to a
      debate as to whether endoscopic retrograde cholangiopancreatography (ERCP) should
      be performed before or after cholecystectomy in patients with bile duct stones.
      METHODS: This study evaluated the efficacy of treatment of
      cholecystocholedocholithiasis in a single step by performing ERCP during surgery
      in 52 patients (35 women, 17 men; mean age 57.0 years; age range 20 to 89 years).
      Laparoscopic intraoperative cholangiography via the cystic duct was carried out
      to confirm the presence of duct stones. A soft-tipped guidewire was passed
      through the cystic duct and papilla into the duodenum. A papillotome was inserted
      endoscopically over the guidewire. Endoscopic sphincterectomy was performed and
      the stones removed with balloon and basket catheters. RESULTS: Endoscopic stone
      removal was successful in 94% of cases without complications related to ERCP or
      surgery. Although operative time was lengthened by about 20 minutes, the hospital
      stay was as short and equal to that for simple laparoscopic cholecystectomy (3
      days on average). CONCLUSIONS: The single-step combined endoscopic-laparoscopic
      technique is safe and effective for treatment of patients with gallbladder and
      bile duct stones.

PMID- 11231395
TI  - Mucinous colon cancer.

PMID- 11231396
TI  - Depressed type submucosal invading colon cancer with type V pit pattern.

PMID- 11231398
TI  - Bowel obstruction due to a large ileal lipoma.

PMID- 11231397
TI  - Gastric outlet obstruction due to a large duodenal tubulovillous adenoma.

PMID- 11231399
TI  - A new technique: light-induced fluorescence endoscopy in combination with
      pharmacoendoscopy.
AB  - BACKGROUND: Most cancers and adenomas of the GI tract are easily detected by
      light-induced fluorescence endoscopy (LIFE-GI). However, some tumors are poorly
      visualized by using this technique. To investigate whether the spraying of
      noradrenaline on the lesion provides better visualization of the boundaries of
      neoplasms, the conventional and LIFE-GI endoscopic observations were made before
      and after spraying of nonadrenaline. METHODS: Seven patients with gastric cancers
      were studied. After a conventional fiberscopic examination, a LIFE-GI procedure
      was performed, and then 20 mL of 0.02% noradrenaline solution was sprayed on the
      lesion. RESULTS: The normal mucosa became paler than the tumor after spraying
      noradrenaline, thereby clarifying the tumor boundary in the LIFE-GI image.
      CONCLUSIONS: The combined use of pharmacoendoscopy with LIFE-GI is useful in the
      detection of gastric malignant tumors because it enhances the boundaries of these
      lesions.

PMID- 11231400
TI  - Esophageal stent placement without fluoroscopy.
AB  - BACKGROUND: Access to fluoroscopic equipment is limited in some regions where
      esophageal cancer is common. This report describes a simple method for placement
      of expandable esophageal stents without fluoroscopy. METHODS: Patients with
      dysphagia due to unresectable esophageal cancer underwent esophageal stent
      placement under endoscopic control alone. A colored mark on the stent delivery
      catheter was used to properly position the undeployed stent with respect to the
      proximal end of the tumor. RESULTS: Stent placement was attempted in 70 patients
      and was successful in every case. There were no immediate complications of stent
      placement. Mean dysphagia score decreased from 3.3 before stent placement to 0.5
      at follow-up. There was a trend toward lower dysphagia scores in patients who
      received coated stents. CONCLUSION: Expandable esophageal stents can be
      accurately and safely placed under direct endoscopic control, without
      fluoroscopy.

PMID- 11231401
TI  - A case of gastric plasmacytoma associated with Helicobacter pylori infection:
      improvement of abnormal endoscopic and EUS findings after H. pylori eradication.

PMID- 11231402
TI  - CMV enteritis causing segmental ischemia and massive intestinal hemorrhage.

PMID- 11231403
TI  - Diverticulum-associated colon mass due to Mullerian cyst: detection by barium
      enema but not colonoscopy.

PMID- 11231404
TI  - Schwannoma of the mediastinum diagnosed by EUS-guided fine needle aspiration.

PMID- 11231405
TI  - A case of early-stage primary malignant melanoma of the esophagus.

PMID- 11231406
TI  - Resolution of mediastinal pancreatic pseudocysts with transpapillary stent
      placement.

PMID- 11231407
TI  - Spontaneous regression of an inflammatory pseudotumor of the liver presenting as
      an obstructing malignant biliary tumor.

PMID- 11231408
TI  - Perforation of an esophageal stent into the common carotid artery.

PMID- 11231409
TI  - Inadvertent endoscopic application of a hemoclip to the splenic artery through a
      perforated gastric ulcer.

PMID- 11231410
TI  - Celiac disease and diffuse T-cell lymphoma of the colon.

PMID- 11231411
TI  - Gastropleural fistula caused by incarcerated diaphragmatic herniation of the
      stomach.

PMID- 11231412
TI  - Management of an ileocolic anastomotic stricture using polyvinyl over-the
      guidewire dilators in Crohn's disease.

PMID- 11231413
TI  - A guidewire-assisted technique for removing retained biliary stents with rat
      toothed forceps during endoscopic retrograde cholangiography.

PMID- 11231414
TI  - Sunflower seed rectal bezoar in an adult.

PMID- 11231415
TI  - Abstract thoughts.

PMID- 11231416
TI  - The minimal standard terminology in digestive endoscopy: perspective on a
      standard endoscopic vocabulary.

PMID- 11231417
TI  - What is the role of individual screening in the prevention of digestive cancer?

PMID- 11231418
TI  - Intestinal involvement by metastatic malignant melanoma.

PMID- 11231419
TI  - Primary pneumatosis cystoides intestinalis.

PMID- 11231421
TI  - The planning of clinical studies: random and not so random assignments.

PMID- 11231422
TI  - And the beat goes on.

PMID- 11231423
TI  - Cardiac enzyme elevations after cardiac surgery: the cardiologist's perspective.

PMID- 11231424
TI  - Troponin I in cardiac surgery: marking the future.

PMID- 11231425
TI  - Need for standardization of noninvasive assessment of vascular endothelial
      function.

PMID- 11231426
TI  - Preserved coronary flow reserve in viable myocardium: further evidence for the
      microvascular hypothesis.

PMID- 11231427
TI  - Angiotensin-converting enzyme inhibitor dosing in heart failure: what is optimal?

PMID- 11231428
TI  - Prognostic implications of left ventricular hypertrophy.
AB  - BACKGROUND: To date there has been no comprehensive review of the association
      between left ventricular hypertrophy (LVH) at baseline and subsequent adverse
      clinical events. METHODS: A total of 20 studies (with 48,545 participants)
      published between January 1960 and January 2000, identified through MEDLINE and
      other sources, related baseline electrocardiographic (ECG) or echocardiographic
      data on LVH to subsequent cardiovascular morbidity and all-cause mortality.
      RESULTS: The prevalence of baseline LVH was higher in echocardiographic studies
      than in ECG studies (16%-74% vs 1%-44%, respectively). The adjusted risk of
      future cardiovascular morbidity associated with baseline LVH ranged from 1.5 to
      3.5, with a weighted mean risk ratio of 2.3 for all studies combined. The
      adjusted risk of all-cause mortality associated with baseline LVH ranged from 1.5
      to 8.0, with a weighted mean risk ratio of 2.5 for all studies combined. There
      was a trend toward a worse prognosis among women with baseline LVH compared with
      men. These findings persisted in the various population and ethnic groups
      studied. CONCLUSION: With the exception of one study in dialysis patients, LVH
      consistently predicted high risk, independently of examined covariates, with no
      clear difference in relation to race, presence or absence of hypertension or
      coronary disease, or between clinical and epidemiologic samples. These results
      clarify the strong relation between LVH and adverse outcome and emphasize the
      clinical importance of its detection.

PMID- 11231429
TI  - Design and rationale of the ARBITER trial (Arterial Biology for the Investigation
      of the Treatment Effects of Reducing Cholesterol)--a randomized trial comparing
      the effects of atorvastatin and pravastatin on carotid artery intima-media
      thickness.
AB  - BACKGROUND: As a class, statins are remarkably effective in reducing low-density
      lipoprotein (LDL) cholesterol, and several of these drugs have now been shown to
      reduce coronary heart disease morbidity and mortality. However, several important
      controversies in the use of statins remain to be answered by clinical trials. For
      example, it is controversial whether marked cholesterol reduction to levels below
      100 mg/dL would further reduce the incidence of coronary heart disease.
      Furthermore, concerns about differences among statins for nonlipid effects has
      raised the concern that the assumption of a class effect is premature until head
      to-head clinical trials are completed. METHODS: Arterial Biology for the
      Investigation for the Treatment Effects of Reducing Cholesterol (ARBITER) is a
      single-center, randomized, active-controlled study comparing the efficacy of high
      dose atorvastatin (80 mg/d) and pravastatin (40 mg/d) in patients being treated
      for either the primary or secondary prevention of coronary heart disease. This
      trial will enroll up to 200 patients for the primary end point of the mean change
      in intima-media thickness of the common carotid artery. This effect will be
      evaluated over a treatment duration of 12 months. Secondary end points include
      the effects of statin therapy on inflammatory and hemostatic markers (C-reactive
      protein and fibrinogen). CONCLUSION: ARBITER will provide important data on the
      role of marked LDL reduction and the "class effect" theory of statin therapy in
      cardiovascular medicine.

PMID- 11231430
TI  - Dalteparin in combination with abciximab during percutaneous coronary
      intervention.
AB  - BACKGROUND: Despite proved efficacy for either dalteparin or platelet
      glycoprotein IIb/IIIa blockade in improving clinical outcomes of patients with
      non-ST-segment elevation acute coronary syndromes, algorithms guiding concomitant
      therapy with these agents have not been devised. The purpose of this study was to
      assess anticoagulant effect and clinical safety for several dose regimens of
      dalteparin administered in combination with abciximab during percutaneous
      coronary intervention (PCI). METHODS AND RESULTS: Patients undergoing PCI with
      standard dose abciximab received dalteparin as follows: 120 IU/kg subcutaneously
      (SQ) to a maximum of 10,000 U if < or =8 hours before PCI (n = 3); for PCI 8-12
      hours after the SQ dose, an additional 40 IU/kg intravenously (IV) was
      administered (n = 1); for PCI >12 hours after SQ dalteparin or with no prior
      dalteparin therapy, random allocation to 40 (n = 27) or 60 (n = 28) IU/kg IV
      during PCI was performed. Those patients who received 60 IU/kg of dalteparin IV
      had a lower incidence of procedural thrombosis (0% vs 11.1%, P <.01), more
      consistent antithrombotic effect (anti-factor Xa activity) and a similar
      incidence of major bleeding (3.7% vs 2.6%) compared with patients who received 40
      IU/kg of intravenous dalteparin. CONCLUSIONS: Dalteparin 60 IU/kg IV appears to
      be safe and effective when administered in conjunction with abciximab for
      percutaneous coronary intervention.

PMID- 11231431
TI  - Rheolytic thrombectomy during percutaneous revascularization for acute myocardial
      infarction: experience with the AngioJet catheter.
AB  - BACKGROUND: Although balloon angioplasty and stenting are effective in the
      treatment of acute myocardial infarction (MI), reduced coronary flow and distal
      embolization frequently complicate interventions when thrombus is present.
      Adjunctive treatment with mechanical thrombectomy devices may reduce these
      complications. METHODS AND RESULTS: We evaluated the angiographic and clinical
      outcomes of 70 patients with acute MI (16% with cardiogenic shock) and with
      angiographically evident thrombus who were treated with AngioJet rheolytic
      thrombectomy followed by immediate definitive treatment. Procedure success
      (residual diameter stenosis <50% and Thrombolysis in Myocardial Infarction [TIMI]
      flow > or =2 after final treatment) was achieved in 93.8%. Clinical success
      (procedure success without major in-hospital cardiac events) was achieved in
      87.5%, with an in-hospital mortality rate of 7.1%. Final TIMI 3 flow was achieved
      in 87.7%. AngioJet treatment resulted in a mean thrombus area reduction from 73.2
      +/- 64.6 mm(2) at baseline to 15.5 +/- 30.1 post-thrombectomy (P <.001).
      Subsequent definitive treatment included stenting in 67% and balloon angioplasty
      alone in 26% of patients. Procedural complications included distal embolization
      in six patients and perforation in two patients. There were no further major
      adverse events during 30-day follow-up. CONCLUSION: Rheolytic thrombectomy can be
      performed safely and effectively in patients with acute MI, allowing for
      immediate definitive treatment in thrombus-containing lesions.

PMID- 11231432
TI  - A nonischemic electrocardiogram does not always predict a small myocardial
      infarction: results with acute myocardial perfusion imaging.
AB  - BACKGROUND: A nonischemic electrocardiogram (ECG) in association with myocardial
      infarction (MI) indicates a small MI in some but not all cases. Myocardial
      perfusion imaging using technetium-99m sestamibi offers the ability to better
      characterize these "electrically silent" infarctions. METHODS: Patients
      considered low risk for myocardial infarction with a normal or nonischemic ECG
      (no significant ST elevation, ST depression, ischemic T-wave inversion, or left
      bundle branch block) underwent early emergency department perfusion imaging,
      followed by serial myocardial marker sampling. Risk area (defect size) was
      quantitated by use of a 50% threshold from multiple short-axis slices. RESULTS: A
      total of 87 patients with nonischemic ECGs had myocardial infarction (mean peak
      creatine kinase [CK] 710 +/- 720 U/L, range 111-3196 U/L). Peak CKs were lower in
      the 7 patients with negative perfusion imaging (420 +/- 290 U/L vs 730 +/- 740
      U/L, P =.06). Mean risk area was 18% +/- 11% of the left ventricle (range 0%-62%)
      and was not significantly different among the different infarct-related arteries.
      Patients with normal ECGs had a similar risk area compared with other patients
      (16% +/- 12% vs 19 +/- 12%, P =.25). Coronary angiography was performed in 81
      patients, with significant stenoses in 74 (91%) (37 one-vessel, 19 two-vessel, 18
      three-vessel), with the infarct related artery most commonly the left circumflex
      (n = 32 [38%]). CONCLUSIONS: The ischemic risk area in patients with a
      nonischemic ECG was comparable to patients with inferior ST-elevation myocardial
      infarction found in previous studies. A nonischemic ECG does not predict a small
      ischemic risk area.

PMID- 11231433
TI  - Utility of B-natriuretic peptide as a rapid, point-of-care test for screening
      patients undergoing echocardiography to determine left ventricular dysfunction.
AB  - BACKGROUND: Although echocardiography is an important tool for making the
      diagnosis of left ventricular (LV) dysfunction, the cost of this procedure limits
      its use as a routine screening tool for this purpose. Brain natriuretic peptide
      (BNP) accurately reflects ventricular pressure, and preliminary studies have
      found it to be highly sensitive and highly specific in diagnosing congestive
      heart failure in the emergency department. We hypothesized that BNP might
      therefore be useful as a screening tool before echocardiography in patients with
      suspected LV dysfunction. METHODS: Subjects included patients referred for
      echocardiography to evaluate the presence or absence of LV dysfunction. Patients
      with known LV dysfunction were excluded from analysis. BNP was measured by a
      point-of-care immunoassay (Biosite Diagnostics, San Diego, Calif). The results of
      BNP levels were blinded from cardiologists making the assessment of LV function.
      Patients were divided into those with normal ventricular function, abnormal
      systolic ventricular function, abnormal diastolic function, and evidence of both
      systolic and diastolic dysfunction. RESULTS: Two hundred patients in whom LV
      function was unknown were studied. In the 105 patients (53%) whose ventricular
      function was subsequently determined to be normal by echocardiography, BNP levels
      averaged 37 +/- 6 pg/mL. This was significantly less than in those patients with
      either ultimate diastolic dysfunction (BNP 391 +/- 89 pg/mL (P <.001) or systolic
      dysfunction (BNP 572 +/- 115 pg/mL (P <.001). A receiver-operator characteristic
      curve showing the sensitivity and specificity of BNP against the echocardiography
      diagnosis revealed the area under the curve (accuracy) was 0.95. At a BNP level
      of 75 pg/mL was 98% specific for detecting the presence or absence of LV
      dysfunction by echocardiography. CONCLUSIONS: A simple, rapid test for BNP, which
      can be performed at the bedside or in the clinic, can reliably predict the
      presence or absence of LV dysfunction on echocardiogram. The data indicate that
      BNP may be an excellent screening tool for LV dysfunction and may, in fact,
      preclude the need for echocardiography in many patients.

PMID- 11231434
TI  - Use of electron beam tomography data to develop models for prediction of hard
      coronary events.
AB  - BACKGROUND: Prediction of hard cardiac events (myocardial infarction and coronary
      death) remains difficult in spite of the identification of several relevant risk
      factors for the development of coronary artery disease (CAD). New indicators of
      risk might add to our predictive ability. We used measures of coronary artery
      calcification (CAC) found by electron beam tomography (EBT) imaging to develop
      prediction models for hard cardiac events alone and in association with
      traditional risk factors for CAD. METHODS: Two groups of patients were studied:
      group A, 676 asymptomatic patients (mean age 52 years, 51% men) prospectively
      followed up for 32 +/- 7 months after being referred by primary care physicians
      for a screening EBT, and group B, 10,122 asymptomatic patients screened by EBT at
      one center and used as controls for calculation of calcium score nomograms.
      RESULTS: The occurrence of hard events in group A patients was related to
      traditional risk factors for CAD, presence of CAC (score >0), Ln (1 + absolute
      calcium score [CS]), and age- and sex-specific CS percentiles (CS%). Univariate
      analyses showed that age, smoking, diabetes mellitus, presence of CAC, Ln (1 +
      absolute CS), and CS% were predictive of hard events (all P <.05). Multiple
      logistic regression analyses demonstrated that CS% was the only significant
      predictor of events and provided incremental prognostic value when added to
      traditional risk factors for CAD (chi-square, P <.001). In a comparison of
      receiver-operator characteristic curves for prediction of hard events, the area
      under the curve for CS% plus conventional risk factors and age was significantly
      larger than that obtained by use of traditional risk factors and age separately
      as predictors (0.84 vs 0.71, respectively, P <.001). Furthermore, the area under
      the curve of CS% alone was significantly larger than that of traditional risk
      factors and age combined (0.82 vs 0.71, P =.028). CONCLUSIONS: Patients are
      usually selected for EBT screening on the basis of the presence of conventional
      risk factors for CAD. However, an age- and sex-specific calcium score provides
      the best predictive model for the occurrence of hard coronary events and adds
      incremental prognostic information to conventional risk factors for CAD.

PMID- 11231435
TI  - Gated single-photon emission computed tomographic myocardial imaging: a new tool
      in clinical cardiology.
AB  - BACKGROUND: Gated single-photon emission computed tomography (gated SPECT)
      myocardial perfusion imaging allows the analysis of left ventricular (LV)
      perfusion and function during the same acquisition. RESULTS: Gated SPECT provides
      additional information to myocardial perfusion, which improves test specificity
      in patients with known or suspected coronary artery disease and hence diminishes
      the amount of borderline diagnosis. Because gated SPECT provides reliable
      information on LV ejection fraction and LV volumes, it is also a valuable tool in
      risk stratification. In addition, from gated SPECT, images can be reconstructed
      from which wall motion can be assessed showing a good correlation with wall
      motion assessed by accepted imaging modalities as echocardiography, magnetic
      resonance imaging, and contrast angiography. In the future wall motion analysis
      from gated SPECT may also be used for revascularization stratification.
      CONCLUSIONS: Gated SPECT gives important additional information beyond myocardial
      perfusion imaging alone, which could have major clinical implications for optimal
      patient management.

PMID- 11231436
TI  - Variation in patient management and outcomes for acute coronary syndromes in
      Latin America and North America: results from the Platelet IIb/IIIa in Unstable
      Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial.
AB  - BACKGROUND: Although more than 9500 patients have been enrolled in major clinical
      trials in Latin America, practice patterns in this region have rarely been
      examined. We sought to compare characteristics, resource utilization, and
      outcomes of patients treated for acute coronary syndromes in Latin America with
      those in North America. METHODS: The Platelet IIb/IIIa in Unstable Angina:
      Receptor Suppression Using Integrilin Theraphy Trial (PURSUIT) enrolled 10,948
      patients with non-ST-segment elevation acute coronary syndromes, including 585 in
      Latin America and 4358 in North America. We analyzed regional differences in
      patient groups, treatment patterns, and outcomes and used logistic regression
      analysis to identify association of enrollment region and survival. RESULTS: For
      patients in Latin America, the length of hospital stay was significantly longer
      (10 [7, 15] days vs 6 [4, 9], P <.001). Angiograms, angioplasty, and bypass
      surgery were significantly less common in Latin America (46.2%, 17.6%, and 11.3%
      vs 79.4%, 33.6%, and 19.4%, P <.001). Thirty-day death/myocardial infarction was
      not significantly higher, although mortality alone was significantly higher (6.8%
      vs 3.1%, P <.001). After adjustment for baseline characteristics, enrollment in
      Latin America remained an independent predictor for death at 30 days (odds ratio
      [OR] [95% confidence interval (CI)] 2.42 [1.60-3.67]) and persisted at 6 months
      (OR [95% CI] 2.5 [1.8-3.4]). CONCLUSIONS: Latin American patients treated for
      acute coronary syndromes were managed less invasively and were twice as likely as
      their North American counterparts to die within 6 months. This mortality
      difference was not explained by imbalances in baseline risk.

PMID- 11231437
TI  - Comparative 30-day economic and clinical outcomes of platelet glycoprotein
      IIb/IIIa inhibitor use during elective percutaneous coronary intervention:
      Prairie ReoPro versus Integrilin Cost Evaluation (PRICE) Trial.
AB  - OBJECTIVES: This study examined the economics, pharmacodynamics, and clinical
      outcomes among patients randomly assigned to receive either abciximab (ReoPro,
      Centocor, Inc, Malvern, Pa, and Eli Lilly & Company, Indianapolis, Ind) or
      eptifibatide (Integrilin, COR Therapeutics, Inc, South San Francisco, Calif, and
      Key Pharmaceuticals, Inc, Kenilworth, NJ) therapy during elective percutaneous
      coronary intervention (PCI). BACKGROUND: Clinical and safety outcomes after
      elective PCI with a high-dose eptifibatide treatment strategy have not previously
      been systematically evaluated. In addition, comparative economic and
      pharmacodynamic studies of platelet glycoprotein (GP) IIb/IIIa receptor
      antagonists during PCI are sparse. METHODS: This randomized, double-blind study
      assessed the 30-day economic and clinical outcomes of 320 consecutive patients
      undergoing elective coronary balloon angioplasty or stent implantation who were
      randomly assigned to receive adjunct abciximab (n = 163) or eptifibatide (n =
      157) therapy. The primary study end point was total in-hospital costs based on an
      intention-to-treat analysis. A secondary end point included 30-day total hospital
      costs. A platelet aggregometry substudy was performed on 155 patients (abciximab:
      n = 74 and eptifibatide: n = 81) with use of the Ultegra Rapid Platelet Function
      Assay. RESULTS: Baseline demographic, angiographic, and procedural variables were
      similar between the two treatment groups. The median and interquartile ranges of
      total in-hospital costs were $8268 ($6505, $9958) and $7207 ($5659, $9307),
      respectively, between the abciximab- and eptifibatide-treated patients (P =.009).
      Median total costs at 30 days were $8336 ($6505, $10,126) and $7207 ($5659,
      $9431), respectively, between the abciximab- and eptifibatide-treated groups (P
      =.009). The composite secondary clinical end points (death/nonfatal myocardial
      infarction/urgent revascularization) occurred in 4.9% versus 5.1% of patients,
      respectively, by hospital discharge (P =.84) and in 5.6% versus 6.3% of patients,
      respectively, at 30 days (P =.95) in the abciximab and eptifibatide groups. With
      the eptifibatide dose used, early and more durable platelet inhibition was
      achieved compared with abciximab (P <.00001). CONCLUSION: In drug dosages and
      patients similar to those enrolled in the current study, eptifibatide achieved
      durable platelet inhibition throughout drug infusion and was associated with
      lower in-hospital and 30-day costs compared with abciximab in patients undergoing
      elective PCI.

PMID- 11231438
TI  - Angiotensin-converting enzyme inhibitor dosages in elderly patients with heart
      failure.
AB  - BACKGROUND: We sought to describe the dosages of angiotensin-converting enzyme
      (ACE) inhibitor prescribed to elderly patients with heart failure at hospital
      discharge, the factors associated with dosing level, and the association of these
      dosages with 1-year outcomes. METHODS: Demographic, procedural, and medication
      data were collected retrospectively from medical records at 18 Connecticut
      hospitals. Information on mortality and readmission was obtained from the Health
      Care Financing Administration administrative databases. Dosages of ACE inhibitor
      were grouped into 3 categories: dosages recommended in practice guidelines or
      higher (target dose), dosages used in clinical trials but lower than guideline
      recommendations (subtarget dose), and dosages lower than those used in clinical
      trials (low dose). RESULTS: A total of 554 patients, 65 years old or less with
      confirmed heart failure and systolic dysfunction, were prescribed an ACE
      inhibitor at discharge. Target, subtarget, and low doses were given in 19%, 63%,
      and 18% of the patients, respectively. Few demographic or clinical factors were
      related to lower dosages. Both subtarget and target doses of ACE inhibitors were
      associated with a significantly lower adjusted 1-year mortality (relative risk
      0.67, P =.04; relative risk 0.51, P =.02, respectively) compared with low doses
      of ACE inhibitors. CONCLUSIONS: In a representative elderly cohort of patients
      with heart failure with systolic dysfunction, the majority (82%) were discharged
      on doses of ACE inhibitors consistent with those used in clinical trials. We
      observed a dose-response relationship between higher doses and lower mortality.
      Future studies will need to determine whether this association is causal.

PMID- 11231439
TI  - Effect of metoprolol on cytokine levels in chronic heart failure--a substudy in
      the Metoprolol Controlled-Release Randomised Intervention Trial in Heart Failure
      (MERIT-HF).
AB  - BACKGROUND: Enhanced immune activation has been suggested to be involved in the
      pathogenesis of congestive heart failure (CHF). There is evidence for
      interactions between the sympathetic nervous system and the immune system. We
      therefore examined the effect of the selective beta(1)-receptor blocker
      metoprolol on various immunologic variables in CHF. METHODS: Eighty-one patients
      with CHF were randomized to metoprolol or placebo in a double-blind trial. Plasma
      levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, soluble
      IL-2 receptor (sIL-2R), monocyte chemoattractant peptide-1, and IL-8 were
      measured at baseline, after 3 months, and at the end of the study (11.4 +/- 0.4
      months). RESULTS: Our main findings were (1) at baseline TNF-alpha, IL-6, IL-8,
      monocyte chemoattractant peptide-1, and sIL-2R but not IL-10 levels were markedly
      elevated in patients with CHF compared with controls; (2) during treatment with
      metoprolol, but not with placebo, there was a significant decrease in sIL-2R
      after 3 months, with a return to baseline at the end of the study; and (3) levels
      of all other immunologic variables remained unchanged throughout the study in
      both the metoprolol and the placebo groups. CONCLUSIONS: Our findings suggest
      that metoprolol treatment in CHF is associated with a significant but temporary
      decrease in sIL-2R, possibly reflecting down-modulation of T-cell activation.
      However, an enhanced immune activation also persisted in the metoprolol group,
      suggesting a potential for more specific immunomodulatory therapy in CHF.

PMID- 11231441
TI  - Right ventricular diastolic function in beta-thalassemia major: echocardiographic
      and clinical correlates.
AB  - BACKGROUND: Cardiac hemochromatosis remains the most frequent cause of death in
      beta-thalassemia major. Previous studies suggest an important right ventricular
      (RV) contribution to cardiac morbidity and mortality. Studies with Doppler
      echocardiography have shown contradictory results regarding left ventricular (LV)
      filling, whereas the RV filling characteristics have not been studied yet. We
      prospectively studied the pattern of RV filling and investigated
      echocardiographic and clinical correlates during baseline and follow-up
      examinations in patients with beta-thalassemia major. METHODS AND RESULTS: The
      study included 79 patients, aged 24.2 +/- 8.0 years, with homozygous beta
      thalassemia major without symptoms of heart failure with normal LV function and
      51 healthy control subjects, matched for age, sex, and body surface area. Doppler
      echocardiographic indexes of systolic and diastolic ventricular function were
      assessed. Hemodynamic measurements were obtained in 8 patients by right heart
      catheterization. An abnormal RV relaxation pattern was evident in the patient
      group. The LV filling characteristics indicated increased preload without
      abnormal alteration, whereas catheterization findings were consistent with a high
      cardiac output state. Short tricuspid deceleration time (DT) had the best
      predictive value for subsequent cardiac events. Repeat echocardiographic study in
      35 asymptomatic patients at 19 +/- 7 months demonstrated deterioration of LV
      systolic function, chamber enlargement, and shortening of DT of tricuspid and
      mitral inflow. CONCLUSIONS: In patients with homozygous beta-thalassemia major
      without cardiac disease, the pattern of RV filling is abnormally altered,
      indicating impaired relaxation. In contrast, the LV filling is compatible with
      increased preload, as in chronic anemia. Short DT of early tricuspid inflow
      carries important prognostic value. LV remodeling occurs over time along with
      transition toward a restrictive ventricular filling pattern.

PMID- 11231440
TI  - Systemic and renal effects of atrial natriuretic peptide in patients with heart
      failure treated with angiotensin-converting enzyme inhibitor or in acute saline
      solution loading.
AB  - BACKGROUND: Our purpose was to study the effects of atrial natriuretic peptide
      (ANP) on cardiorenal functions when it is used to manage patients with heart
      failure who are receiving an angiotensin-converting enzyme inhibitor (ACEi) or in
      acute saline solution loading. METHODS: Seventeen patients with mild to moderate
      heart failure were entered into protocol 1 or 2. Protocol 1 was ANP (30
      ng/kg/min) infused before and after treatment with ACEi (n = 9). Protocol 2 was
      acute saline loading with or without coadministration of ANP (n = 8). In both
      protocols cardiorenal hemodynamics and urinary sodium excretion were assessed
      before and after each intervention. RESULTS: Protocol 1: Although ANP infusion
      significantly increased urinary sodium excretion to a similar extent before and
      after ACEi treatment, the infusion increased the glomerular filtration rate (75
      +/- 16 --> 82 +/- 15 mL/min, P <.05) and renal blood flow (390 +/- 123 --> 438 +/
      140 mL/min, P <.05) only before ACEi treatment. Protocol 2: Acute saline
      solution loading decreased plasma renin activity (P <.05) but did not affect ANP
      level. Coadministration of ANP with saline solution load enhanced the increase of
      urinary sodium excretion (75% +/- 34% increase) compared with the acute saline
      solution load alone (49% +/- 33% increase) (P <.05) but had no affect on renal
      hemodynamics. CONCLUSIONS: When ANP is used in patients with mild to moderate
      heart failure who are on combined ACEi treatment or in acute saline solution
      loading, the vasodilatory effect of ANP is blunted while the natriuretic effect
      of ANP is preserved. The renin-angiotensin system seems to modulate the
      vasodilatory effect of ANP.

PMID- 11231442
TI  - Elevated interleukin-6 levels in patients with asymptomatic left ventricular
      systolic dysfunction.
AB  - BACKGROUND: Elevated interleukin-6 (IL-6) levels are present in patients with New
      York Heart Association (NYHA) class III and IV congestive heart failure (CHF) and
      are associated with a poor prognosis. We sought to determine whether elevated IL
      6 levels are also present in patients with left ventricular (LV) dysfunction but
      without clinical symptoms. METHODS: Blood samples were obtained from the femoral
      artery of 58 patients who underwent cardiac catheterization for recognized
      clinical indications. In a subgroup of 44 patients, samples were also obtained
      from the femoral vein, the left main coronary artery, and the coronary sinus.
      Patients with prior coronary artery bypass surgery, recent acute coronary
      syndrome, or steroid therapy were excluded. All samples were obtained before
      heparin or contrast administration. IL-6 was measured by enzyme-linked
      immunosorbent assay and values are expressed in picograms per milliliter.
      RESULTS: Three groups of patients were identified: controls, no CHF, LV ejection
      fraction >/=0.55 (n = 32); asymptomatic LV systolic dysfunction, no CHF, LV
      ejection fraction <0.55 (n = 14); and CHF, pulmonary edema (n = 12). IL-6 levels
      were higher at all sampling sites in both the asymptomatic LV systolic
      dysfunction and CHF groups compared with controls with the IL-6 levels inversely
      related to LV ejection fraction. CONCLUSIONS: Elevated IL-6 levels are present in
      patients with LV dysfunction even in the absence of the clinical syndrome of CHF.
      These data suggest that IL-6 may be involved in the progression of subclinical LV
      dysfunction to clinical CHF. IL-6 may be a marker of patients at risk for
      progression to clinical CHF or a novel target for therapeutic intervention.

PMID- 11231443
TI  - A population-based assessment of left ventricular systolic dysfunction in middle
      aged and older adults: the Strong Heart Study.
AB  - BACKGROUND: Although clinical congestive heart failure (CHF) is increasingly
      common, few data document the prevalence and correlates of underlying left
      ventricular (LV) systolic dysfunction (D) in population-based samples. METHODS:
      Echocardiography was used in the second Strong Heart Study (SHS) examination to
      identify mild and severe LVD (LV ejection fraction [EF] 40%-54% and <40%,
      respectively) in 3184 American Indians. RESULTS: Mild and severe LVD were more
      common in men than women (17.4% vs 7.2% and 4.7% vs 1.8%) and in diabetic than
      nondiabetic participants (12.7% vs 9.1% and 3.5% vs 1.6%). Stepwise increases
      were observed from participants with normal EF to those with mild and severe LVD
      in age (mean 60 vs 61 and 63 years, P <.001), prevalence of overt CHF (2% vs 6%
      and 28%) and definite coronary heart disease (3% vs 11% and 32%), systolic
      pressure (129 vs 135 and 136 mm Hg), serum creatinine level (0.98 vs 1.34 and
      2.16 mg/dL), and log urinary albumin/creatinine level (3.2 vs 3.7 and 4.7); a
      negative relation was seen with body mass index (31.1 vs 31.0 and 28.4 kg/m(2))
      (all P <.001). In multivariate analyses lower LVEFs were independently associated
      with clinical CHF and coronary heart disease, lower myocardial contractility,
      male sex, hypertension, overweight, arterial stiffening (higher pulse
      pressure/stroke volume) and renal dysfunction (higher serum creatinine level),
      higher LV mass, and lower relative wall thickness. CONCLUSIONS: LVD, present in
      approximately 14% of middle-aged to elderly adults, is independently associated
      with overt heart failure and coronary heart disease, male sex, hypertension,
      overweight, arterial stiffening, and renal target organ damage and, less
      consistently, with older age and diabetes.

PMID- 11231444
TI  - Usefulness of cardiac troponin I in patients undergoing open heart surgery.
AB  - BACKGROUND: Significant myocardial injury during cardiac surgery is associated
      with a 10-fold increase in 2-year complication rates, yet there remains no
      clinical gold standard for diagnosis. Troponin I has complete cardiospecificity
      and is clinically used for diagnosis of myocardial infarction in other settings.
      METHODS AND RESULTS: One hundred consecutive patients undergoing open heart
      surgery (71 coronary artery bypass grafts and 29 aortic valve replacements) were
      enrolled and blood samples were drawn preoperatively, at 5 AM and 5 PM on days 1
      and 2 after surgery, and at 5 AM for 3 more days. Twelve-lead electrocardiograms
      were performed daily and echocardiographic studies were performed on patients
      with either; electrocardiographic changes signifying likely myocardial damage,
      intraoperative complications, or elevated creatine kinase subfraction MB or
      troponin values. Seventeen patients had either new wall motion abnormalities or
      new Q waves all with peak cardiac troponin I >40 ng/mL. Stratification of
      patients by peak troponin values <40 and >60 ng/mL was highly predictive (P
      <.001) of days in intensive care unit, days on ventilator, development of new
      arrhythmia, and especially cardiac events. These postoperative variables also
      showed a stronger correlation with peak cardiac troponin I than did peak creatine
      kinase subfraction MB. CONCLUSION: Peak troponin I values detect myocardial
      infarction the day after heart surgery and predicts patient outcome.

PMID- 11231445
TI  - Relationship between extent of residual myocardial viability and coronary flow
      reserve in patients with recent myocardial infarction.
AB  - BACKGROUND: The presence of viability in an infarct zone implies an intact
      microvasculature. We hypothesized that coronary flow reserve (CFR), which
      assesses the microcirculation, would correlate with the extent of viability in
      infarction zones. METHODS: CFR was measured after stenting in 17 patients with
      single vessel disease >48 hours from infarction. Viability was determined with
      use of single-photon emission computed tomography sestamibi imaging. RESULTS:
      Sestamibi uptake in the infarct zone correlated with CFR in the infarct artery (r
      = 0.62, P =.008) and sestamibi uptake in the infarct zone was greater in patients
      with normal CFR than in patients with abnormal CFR (61.9 +/- 9.1% vs 46.3 +/-
      9.6%, P =.004). In addition, CFR was greater in patients with viability compared
      with patients without viability (2.4 +/- 1.3 vs 1.4 +/- 0.4, P =.015).
      CONCLUSIONS: CFR correlates with the extent of viability after infarction.
      Preserved CFR in an infarct-related artery implies preserved viability.

PMID- 11231446
TI  - Do conventional risk factors predict subclinical coronary artery disease? Results
      from the Prospective Army Coronary Calcium Project.
AB  - BACKGROUND: Recent guidelines recommend against the routine use of coronary
      artery calcification (CAC) detection because the additive value over clinical
      prediction tools is uncertain. We compared CAC, with use of electron-beam
      computed tomography (EBCT), with clinical and serologic coronary risk factors for
      the identification of patients with increased coronary heart disease risk.
      METHODS AND RESULTS: We studied 630 active-duty US Army personnel (39-45 years
      old) without known coronary artery disease (CAD) who were undergoing a routine
      physical examination as required by regulations. Each participant underwent
      clinical and serologic risk factor screening and EBCT. The cohort (mean age 42 +/
      2 years, 82% male) had a low predicted risk of coronary events (mean 5-year
      Framingham risk index [FRI] 1.6% +/- 1.2%). The prevalence of coronary
      calcification was 17.6% (male 20.6%, female 4.3%). Significant univariate
      correlates of CAC were total and low-density lipoprotein [LDL] cholesterol,
      triglycerides, systolic blood pressure, and body mass index. However, only LDL
      cholesterol was independently associated with CAC. There was a significant but
      weak relationship between CAC and the Framingham risk index (FRI) (receiver
      operator characteristic [ROC] curve area 0.62 +/- 0.03, P <.001), which was not
      different from the relationship between CAC and LDL cholesterol alone (ROC curve
      area 0.61 +/- 0.03, P <.001). The prevalence of any CAC in men increased slightly
      across increasing quartiles of FRI: 17.0%, 20.8%, 33.0%, and 29.2% (P =.033).
      Other risk factors (family history, homocysteine, insulin, lipoprotein[a], and
      fibrinogen) were not related to CAC. CONCLUSIONS: In this age-homogeneous, low
      risk screening cohort, conventional coronary risk factors significantly
      underestimated the presence of premature, subclinical calcified coronary
      atherosclerosis. These data support the potential of CAC detection as an
      anatomic, plaque-burden diagnostic test to identify patients who may require more
      intensive risk-reduction therapies, independent of predicted clinical risk.

PMID- 11231447
TI  - Outcome of acute ST-segment elevation myocardial infarction in patients with
      prior coronary artery bypass surgery receiving thrombolytic therapy.
AB  - BACKGROUND: Patients with prior coronary bypass surgery with acute ST-segment
      elevation myocardial infarction (MI) pose an increasingly common clinical
      problem. We assessed the characteristics and outcomes of such patients undergoing
      thrombolysis for acute MI. METHODS AND RESULTS: We compared the characteristics
      and outcomes of patients in the Global Utilization of Streptokinase and Tissue
      Plasminogen Activator for Occluded Coronary Arteries trial (GUSTO-I) who had had
      prior bypass (n = 1784, 4% of the population) with those without prior coronary
      artery bypass grafting (CABG), all of whom were randomized to receive one of four
      thrombolytic strategies. Patients with prior bypass were older with significantly
      more prior MI and angina. Overall, 30-day mortality was significantly higher in
      patients with prior bypass (10.7% vs 6.7% for no prior bypass, P <.001); these
      patients also had significantly more pulmonary edema, sustained hypotension, or
      cardiogenic shock. Patients with prior bypass showed a 12.5% relative reduction
      (95% confidence interval, 0% to 41.9%) in 30-day mortality with accelerated
      alteplase over the streptokinase monotherapies. In the 62% of patients with prior
      CABG who underwent coronary angiography, the infarct-related vessel was a native
      coronary artery in 61.9% and a bypass graft in 38.1% of cases. The Thrombolysis
      in Myocardial Infarction (TIMI) 3 flow rate was 30.5% for culprit native coronary
      arteries and 31.7% for culprit bypass grafts. Patients with prior bypass had more
      severe infarct-vessel stenoses (99% [90%, 100%] vs 90% [80%, 99%], P <.001).
      CONCLUSIONS: The 30-day mortality in patients with prior CABG was significantly
      higher than that for patients without prior CABG. As in the overall trial, these
      patients derived an incremental survival benefit from treatment with accelerated
      alteplase, but mortality remained high (16.7%) at 1 year. These results are at
      least partially explained by the higher baseline risk of these patients and by
      the lower rate of patency of the infarct-related artery.

PMID- 11231448
TI  - Impaired fasting glucose concentrations in nondiabetic patients with ischemic
      heart disease: a marker for a worse prognosis.
AB  - BACKGROUND: The issue of whether glucose concentrations below the diabetic
      threshold may be predictive of increased cardiovascular risk has not yet been
      fully elucidated. The current study evaluates the prognosis of nondiabetic
      patients with ischemic heart disease (IHD) and impaired fasting glucose (IFG)
      over a 7.7-year follow-up period. METHODS: A total of 11,853 patients with
      documented coronary artery disease aged between 45 and 74 years were examined.
      Patients were divided into 3 groups on the basis of their fasting blood glucose
      levels at screening: nondiabetic individuals, patients with IFG, and undiagnosed
      diabetic patients. Patients who were on any type of pharmacologic antidiabetic
      treatment were excluded from the study. Mortality rates were assessed separately
      for each group. RESULTS: The population comprised 9773 nondiabetic patients
      (82.4%, glucose up to 109 mg/dL), 1258 patients with IFG levels (10.6%, glucose
      110-125 mg/dL), and 822 diabetic subjects (7%, glucose > or =126 mg/dL). Patients
      were followed up from 6.2 to 9.0 years (mean follow-up period 7.7 +/- 1.5 years).
      Crude mortality was lower in the nondiabetic subjects than in the 2 other groups.
      All-cause mortality in the nondiabetic group was 14.3% compared to 20.1% in
      patients with IFG and 24.3% in the undiagnosed (P <.001). Multivariate adjustment
      showed the lowest mortality in nondiabetic subjects, who exhibited a survival
      rate of 0.86 at the end of the follow-up, whereas the lowest survival-0.75-was
      seen among undiagnosed diabetic patients (P =.0001). An intermediate value of
      0.78 was documented for patients with IFG (P <.01). After multivariate analysis,
      with nondiabetic patients as the reference group, IFG was identified as a
      consistent predictor of increased all-cause and IHD mortality with hazard ratios
      of 1.39 (95% confidence interval 1.21-1.59) and 1.29 (95% confidence interval
      1.01-1.64), respectively. CONCLUSIONS: The main finding of this study is the
      substantially increased mortality rate among nondiabetic coronary patients with
      IFG, who had fasting glucose levels markedly lower than hitherto acknowledged as
      defining overt diabetes.

PMID- 11231449
TI  - Congenital left ventricular aneurysm: clinical, imaging, pathologic, and surgical
      findings in seven new cases.
AB  - BACKGROUND: Congenital left ventricular aneurysm is a poorly understood and
      potentially lethal entity. Methods and Results In a clinicopathologic study of 7
      new cases, the major presenting features in 6 patients were congestive heart
      failure in 4, ventricular arrhythmias in a 32-week fetus, and multiple congenital
      anomalies in a fetus with trisomy 13. Accurate diagnosis was achieved in all 3
      living patients by echocardiography, angiocardiography, and magnetic resonance
      imaging. The aneurysm was predominantly apical in 3 and involved most of the left
      ventricular free wall in 4. Of the 3 living patients, medical management alone
      sufficed in 2. The third, a newborn boy, underwent a new and successful aneurysm
      exclusion left ventriculoplasty. The mitral valve was abnormal in all 4 autopsied
      cases, the papillary muscles being short, thin, or absent. The aneurysm was
      thinner and its area was larger than that of the nonaneurysmal left ventricle in
      all necropsied patients. CONCLUSIONS: Congenital left ventricular aneurysm
      appears to be a developmental anomaly, an idiopathic dysplasia of left
      ventricular endocardium and myocardium. No evidence of a viral etiology was
      found. Some neonates can be managed medically, but others require urgent surgical
      intervention. A new surgical operation is presented, a functional left
      ventricular aneurysmectomy that minimizes intraoperative and postoperative blood
      loss and that preserves the coronary arteries.

PMID- 11231450
TI  - Estimation of pressure gradients by auscultation: an innovative and accurate
      physical examination technique.
AB  - BACKGROUND: Knowledge of pressure gradients across valves, arteries, and
      ventricular septal defects (VSD) is important in patient management. It was
      determined how well such gradients can be estimated by auscultation of a murmur's
      frequencies. METHODS: In 151 patients with pulmonary stenosis (PS) (n = 77),
      aortic stenosis (AS) (n = 30), or VSD (n = 44), the auscultation gradient was
      estimated by a murmur's frequencies by use of an "auscultatory scale." The
      auscultation gradient was recorded before Doppler echocardiography was performed
      by a blinded cardiac sonographer. RESULTS: Auscultation correlated highly with
      Doppler echocardiography (Doppler = 0.99. Auscultation + 7.12; r = 0.84, P
      <.0001). Agreement was good (mean difference [Auscultation - Doppler] = -6.8 +/-
      15.8 mm Hg). In 95 patients (63%), agreement was within 10 mm Hg. Auscultation
      was more accurate when Doppler gradients were < or =60 mm Hg (r = 0.76, P <.0001,
      vs r = 0.22, P not significant for >60 mm Hg; mean difference -2.6 +/- 10.6 mm Hg
      vs -16.5 +/- 20.9 mm Hg for >60 mm Hg, P <.0001). Among lesions, PS showed the
      highest correlation, although agreement for PS, AS, and VSD was not significantly
      different. Isolated valvar PS showed excellent accuracy (r = 0.92, P <.0001; mean
      difference -5.6 +/- 8.9 mm Hg). CONCLUSIONS: Auscultation of a murmur's frequency
      composition can estimate gradients accurately in most patients with PS
      (especially valvar PS), AS, or VSD, although it is less accurate for gradients
      >60 mm Hg. This innovative technique can improve diagnostic accuracy, thereby
      further substantiating the value of physical examination.

PMID- 11231451
TI  - Xenotransplantation: just around the corner?

PMID- 11231452
TI  - Direct detection of cellular immune responses to cancer vaccines.
AB  - The evaluation of cancer immunotherapy is predicated on the hypothesis that
      markers of tumor antigen-specific T-cell immunity will cone-late with clinical
      efficacy. Establishing which candidate vaccines should enter large-scale clinical
      trials will necessitate optimal application of immunologic monitoring assays.
      Evidence suggests that available techniques are adequate for the direct detection
      of clinically significant antigen-specific T-cell responses from tissue
      specimens. To achieve this goal, it is important to have an understanding of
      individual methods and their limitations, to include appropriate control antigens
      in the monitoring strategy, and to incorporate statistical considerations into
      the design and analysis of such studies.

PMID- 11231453
TI  - Expression of inducible nitric oxide synthase in the liver of bile duct-ligated
      Wistar rats with modulation by lymphomononuclear cells.
AB  - BACKGROUND: The current study evaluated whether biliary tract obstruction
      stimulates inducible nitric oxide synthase (iNOS) protein expression in the liver
      and analyzed the implication of lymphomononuclear cells and interleukin-4 (IL-4).
      METHODS: Male Wistar rats were used. Bile flow interruption was achieved by a
      complete division of the extrapancreatic common bile duct. iNOS expression was
      determined by both the Western blot technique and immunohistochemistry. RESULTS:
      iNOS protein was markedly expressed in the liver 7 days after bile duct
      obstruction. Treatment with thymostimulin (TP-1), a partially purified thymic
      extract, reduced the intensity of the expression of iNOS protein in the liver
      after bile duct ligation. Recent data have suggested that IL-4 attenuates iNOS
      protein expression. We then analyzed the involvement of this anti-inflammatory
      cytokine on the modulation of iNOS expression in the liver. The liver from rats
      that underwent bile duct ligation (BDL) showed a lower content of IL-4 than that
      of sham-operated (SO) rats. TP-1 treatment increased the content of IL-4 in the
      liver. Liver slices incubated in vitro with Escherichia coli lipopolysaccharide
      (LPS, 10 microg/mL) stimulated the expression of iNOS protein. The level of LPS
      induced iNOS expression was reduced by lymphomononuclear cells obtained from sham
      operated animals. However, lymphomononuclear cells isolated from BDL rats
      potentiated the induction of iNOS expression by LPS-stimulated liver. However,
      lymphomononuclear cells from TP-1-treated BDL rats failed to modify LPS
      stimulated iNOS expression. The different effect of lymphomononuclear cells on
      the modulation of iNOS expression in the liver was associated with their ability
      to generate IL-4. CONCLUSIONS: The liver of jaundiced rats markedly expressed
      iNOS protein, which was associated to modifications in the content of IL-4 in the
      liver. Furthermore, lymphomononuclear cells modulate iNOS protein expression in
      the liver by a mechanism in which IL-4 is involved.

PMID- 11231454
TI  - Retinoic acid receptor-alpha messenger RNA expression is increased and retinoic
      acid receptor-gamma expression is decreased in Barrett's intestinal metaplasia,
      dysplasia, adenocarcinoma sequence.
AB  - BACKGROUND: Expression levels of the retinoic acid receptors (RAR-alpha, RAR
      beta, and RAR-gamma) are significantly different in neoplastic tissues compared
      with non-neoplastic tissues for some tumors. This study investigated whether
      retinoic acid receptor messenger RNA (mRNA) expression levels are altered in
      Barrett's esophagus and Barrett's adenocarcinoma tissues. METHODS: Relative mRNA
      expression levels of the RARs were quantified by using the ABI 7700 Sequence
      Detector (Taqman) system in Barrett's intestinal metaplasia (n = 15), dysplasia
      (n = 6), adenocarcinoma (n = 17), and matching normal esophagus tissues (n = 36).
      RESULTS: RAR-alpha expression was significantly increased, and RAR-gamma
      expression was significantly decreased, at higher stages in the Barrett's
      sequence. There was almost complete loss of RAR-gamma expression (relative
      expression level < or = 1) in a majority (70%) of the dysplasia and
      adenocarcinoma tissues. There were significant differences in RAR-alpha and RAR
      gamma expression in histopathologically normal tissues in patients with cancer
      versus patients without cancer. RAR-beta expression levels were significantly
      elevated in adenocarcinoma versus normal esophagus tissues. The RAR expression
      profile was similar for cancers arising within the esophagus and for cancers
      arising at the gastroesophageal junction. CONCLUSIONS: RAR mRNA expression levels
      are significantly different in Barrett's tissues compared with normal esophagus
      tissues, and these levels are significantly different in Barrett's dysplasia and
      adenocarcinoma tissues compared with nondysplastic tissues. These results suggest
      that RAR mRNA levels may be useful biomarkers for this disease and that
      gastroesophageal junction adenocarcinomas are genetically similar to esophageal
      adenocarcinomas. These results also suggest that a cancer field is present in the
      esophagus in patients with cancer and that genetic alterations can precede
      histopathologic alterations in this disease.

PMID- 11231455
TI  - Intestinal transplantation for the treatment of desmoid tumors associated with
      familial adenomatous polyposis.
AB  - BACKGROUND: Desmoid tumors associated with familial adenomatous polyposis (FAP)
      are locally invasive. Often occurring in the mesentery of the intestine, they
      sometimes recur after resection. Complications can include intestinal failure and
      dependence on parenteral nutrition. We describe 9 patients who underwent
      intestinal transplantation for the treatment of desmoid tumors associated with
      FAP. METHODS: Records of patients undergoing intestinal transplantation for
      desmoid tumors at 2 transplant centers were reviewed for patient age, sex, type
      of graft, procedure date, tumor site, desmoid complications, medications,
      extracolonic manifestations, status at follow-up, and length of survival.
      RESULTS: Nine patients with FAP and intestinal failure caused by desmoid tumors
      were treated with isolated intestinal (n = 6), multivisceral (n = 2), or combined
      liver-intestinal transplantation (n = 1). Desmoid tumors recurred in the
      abdominal walls of 2 patients. Two patients died: one as a result of sepsis, the
      other because of a rupture of a mycotic aneurysm of the aortic anastomosis. One
      graft lost to severe rejection was replaced with a second intestinal graft.
      Eleven to 53 months after transplantation, 7 patients were alive, well,
      independent of parenteral treatment, and leading apparently normal lifestyles.
      CONCLUSIONS: Transplantation of the intestine alone or as part of a multivisceral
      transplantation may help rescue otherwise untreatable patients with complicated
      desmoid tumors.

PMID- 11231456
TI  - The abnormal lipid spectrum in malignant obstructive jaundice in relation to
      endotoxin sensitivity and the result of preoperative biliary drainage.
AB  - BACKGROUND: Biliary obstruction changes the spectrum of lipoproteins, which are
      now known to bind and neutralize endotoxin. Postoperative septic complications
      related to an increased susceptibility to endotoxin occur frequently in patients
      with obstructive jaundice. The effect of preoperative biliary drainage on changes
      in the lipoprotein spectrum and its relation to endotoxin sensitivity was
      studied. METHODS: Abnormalities in the lipoprotein spectrum were assessed in 15
      patients with malignant obstructive jaundice before and 3 weeks after endoscopic
      biliary drainage. Changes in endotoxin responsiveness were assessed by using
      endotoxin-neutralizing reagents (anti-CD14 monoclonal antibody, polymyxin B, and
      recombinant bactericidal permeability increasing protein) to block cytokine
      production in whole blood cell cultures that were stimulated by cholestatic
      plasma taken before and after drainage. RESULTS: Drainage normalized very-low
      density, low-density, and high-density lipoprotein cholesterol fractions from,
      respectively, 43% to 19%, 50% to 65%, and 6% to 16% (P <.01). Ex vivo stimulation
      of whole blood with predrainage cholestatic plasma was 20-fold higher (P <.001)
      than with postdrainage plasma. Blocking the endotoxin response during the
      stimulation with predrainage cholestatic plasma with anti-CD14 monoclonal
      antibody, polymyxin B or recombinant bactericidal permeability increasing protein
      resulted in attenuation of the inflammatory response, reducing tumor necrosis
      factor-alpha levels at least 5-fold. CONCLUSIONS: Preoperative biliary drainage
      normalizes the changed lipid profile and the endotoxin-stimulating capacity of
      cholestatic plasma, and this signifies a change in sensitivity to endotoxin.

PMID- 11231457
TI  - Reduction of inflammatory response in composite flap transfer by local stress
      conditioning-induced heat-shock protein 32.
AB  - BACKGROUND: The failure of composite flaps despite anastomotic patency is thought
      to be mediated by the inflammatory response within the microvasculature, which
      results from unavoidable surgical trauma and transfer-related ischemia
      reperfusion. Evidence suggests that stress conditioning may improve flap
      survival; however, the molecular mechanisms of protection are far from being
      clear. Therefore, we analyzed whether stress conditioning-induced heat-shock
      protein 32 is effective to prevent the inflammatory response in transferred
      osteomyocutaneous flaps. METHODS: In a rat model, leukocyte-endothelial cell
      interaction and endothelial integrity disruption as early indicators of the
      inflammatory response were quantitatively analyzed in muscle, subcuticular
      tissue, and periosteum of microvascularly transferred osteomyocutaneous flaps by
      using intravital fluorescence microscopy. Twenty-four hours before flap transfer,
      stress conditioning was induced by local heating of the left hindlimb up to 42.5
      degrees C for 30 minutes. In additional animals, stress conditioning-induced
      activity of heat-shock protein 32 was inhibited by tin protoporphyrin-IX.
      Unconditioned flaps served as controls. RESULTS: In all tissues analyzed, control
      flaps showed significant leukocyte adherence in postcapillary venules, increased
      intercellular adhesion molecule-1 (ICAM-1) expression, and endothelial integrity
      disruption, but a lack of heat-shock protein 32. In contrast, stress conditioning
      induced marked heat-shock protein 32 expression, which was associated with a
      significant reduction (P <.05) of leukocyte adherence, ICAM-1 expression, and
      endothelial hyperpermeability. The inhibition of heat-shock protein 32 by tin
      protoporphyrin-IX completely abolished the stress conditioning-induced
      amelioration of the inflammatory response in all tissues analyzed. CONCLUSIONS:
      Stress conditioning by local heat-shock priming reduces the inflammatory response
      in osteomyocutaneous flaps. The protective effect is predominantly mediated by
      the induction of heat-shock protein 32.

PMID- 11231458
TI  - Tumor angiogenesis as an independent prognostic factor after extended radical
      esophagectomy for invasive squamous cell carcinoma of the esophagus.
AB  - BACKGROUND: Currently, there is only limited information regarding tumor
      angiogenesis and its clinical implications in cases of esophageal carcinoma. The
      purpose of this study was to clarify which clinicopathologic parameters correlate
      with tumor angiogenesis; furthermore, the study was conducted to evaluate whether
      tumor angiogenesis is an independent prognostic factor in cases of esophageal
      carcinoma. METHODS: Intratumoral microvessel density (MVD) and thymidine
      phosphorylase (dThdPase) expression were immunohistochemically studied after
      extended radical esophagectomy in 103 cases of esophageal carcinoma. RESULTS:
      Increased MVD significantly correlated with the depth of tumor invasion, the
      frequency of intramural metastasis, and the stage of tumor advancement (P <.05).
      dThdPase expression status significantly correlated with the size and depth of
      primary tumors (P <.02). A significant correlation was present between MVD and
      the expression status of dThdPase (P <.01). Furthermore, increased MVD correlated
      with increased tumor recurrence after esophagectomy and with poorer survival
      curves (P <.01 and P <.05, respectively). A multivariate analysis revealed MVD to
      be an independent predictor of unfavorable prognosis. CONCLUSIONS: Tumor
      angiogenesis expressed as MVD correlates with clinicopathologic parameters
      regarding tumor progression and is an independent prognostic indicator in
      patients undergoing extended radical esophagectomy for invasive esophageal
      carcinoma.

PMID- 11231459
TI  - Effect of FR167653 on pancreatic ischemia-reperfusion injury in dogs.
AB  - BACKGROUND: The role of inflammatory cytokines is still unclear in ischemia
      reperfusion injury of the pancreas. We investigated the effect of FR167653 (FR),
      a newly developed compound that is a potent suppressor of interleukin (IL)-1beta
      and tumor necrosis factor (TNF)-alpha on ischemia-reperfusion injury of the
      isolated pancreatic tail in dogs. METHODS: The tail of the pancreas was subjected
      to ischemia for 90 minutes. During occlusion of the vascular inflow, the head of
      the pancreas was removed. A control group (n = 14) and an FR treatment group (n =
      11) were evaluated for survival rate, tissue blood flow, arterial oxygen pressure
      (Pao(2)), serum amylase and lipase levels, glucose and insulin, liver enzymes,
      creatinine, IL-1beta mRNA in the peripheral blood, and histopathology. RESULTS:
      Six of the 14 control animals and 2 of the 11 FR-treated animals died. The FR
      treatment group showed lower amylase (P=.037) and lipase (P =.030) levels, lower
      IL-1beta mRNA expression (P =.033), and less pancreatic tissue damage (P =.041)
      than did the control group, but there was no remarkable change in endocrine
      function (P =.422). Pao(2) during the acute phase in the FR treatment group was
      maintained (P=.009), but pulmonary tissue was damaged. Results of biochemical and
      histologic examinations of the liver and kidneys were unremarkable. CONCLUSIONS:
      FR ameliorates ischemia-reperfusion injury of the pancreas and reduces the
      production of inflammatory cytokines that may contribute to secondary damage to
      distant organs.

PMID- 11231460
TI  - Routine parathyroid autotransplantation during thyroidectomy.
AB  - BACKGROUND: Parathyroid autotransplantation (PTHAT) during thyroidectomy has been
      shown to reduce the incidence of permanent hypoparathyroidism. Although selective
      PTHAT is most commonly adopted, the value of routine PTHAT has not been well
      documented. METHODS: From January, 1998 to March, 1999, an operative strategy
      incorporating routine autotransplantation of at least 1 parathyroid gland was
      used during thyroidectomy. The postoperative outcome of patients (n = 118) was
      evaluated and compared with patients (n = 271) operated during a policy of
      selective PTHAT (January, 1995 to October, 1997). RESULTS: Two or more
      parathyroid glands were autotransplanted in 26 patients (22%) while 92 patients
      (78%) received autotransplantation of 1 parathyroid gland. Postoperative
      hypocalcemia occurred in 29 patients (25%) and 2 patients (1.7%) had permanent
      hypocalcemia develop. When a policy of selective PTHAT was adopted, 98 patients
      (36%) underwent PTHAT, and 5 patients developed permanent hypocalcemia (1.8%).
      The incidence of postoperative hypocalcemia was higher in patients who underwent
      routine PTHAT (25%) compared with that in patients who underwent selective PTHAT
      (15%) (P =.014). In addition, the operating time was significantly longer when
      routine PTHAT was adopted (153 minutes vs 130 minutes; P <.001). CONCLUSIONS: A
      low incidence of permanent hypoparathyroidism can be achieved by either routine
      or selective PTHAT during thyroidectomy but routine PTHAT is associated with a
      high incidence of postoperative hypocalcemia.

PMID- 11231461
TI  - Specific organ gene transfer in vivo by regional organ perfusion with herpes
      viral amplicon vectors: implications for local gene therapy.
AB  - BACKGROUND: Many gene therapy strategies would benefit from efficient, regional
      organ delivery of therapeutic genes. METHODS: Regional perfusions of lung, liver,
      or bladder were performed to determine if rapid and efficient gene transfer can
      be accomplished in vivo, and to determine if in vivo gene transfer can be limited
      to the organ of interest. In addition, herpes simplex virus tumor necrosis factor
      (HSVtnf), carrying the human tumor necrosis factoralpha gene was used as a
      treatment for methylcholanthrene sarcoma in a syngeneic lung metastases model in
      Fisher rats. RESULTS: A 20-minute perfusion using HSV carrying beta-galactosidase
      (HSVlac) produced significant expression of this marker gene isolated to the
      target organs, without organ-specific tissue injury or inflammation. Regional
      perfusion of organs with HSV carrying the cytokine gene tumor necrosis factor
      alpha also resulted in high-level local organ production of this cytokine (2851
      +/- 53 pg/g tissue in perfused lung versus 0 for the contralateral lung). For the
      current vector construct, expression of the gene of interest peaked between 2 and
      4 days and was undetectable by 2 weeks after perfusion. In animals undergoing
      perfusion as treatment for pulmonary sarcoma, there was no difference between
      tumor counts in lungs perfused with HSVlac (17 +/- 6) or HSVtnf (22 +/- 8), but
      either treatment resulted in lower tumor counts than controls (111 +/- 24 nodules
      per lung, P <.02). CONCLUSIONS: Regional organ perfusion using herpes viral
      vectors is an effective and well-tolerated in vivo method of transiently
      delivering potentially toxic gene products to target organs in directing gene
      therapy. Regional lung perfusion with HSV amplicons reduces tumor burden in a rat
      model of pulmonary metastases, though HSVtnf cannot be demonstrated to augment
      the cytopathic effect of the HSV amplicon alone in the current model.

PMID- 11231462
TI  - Application of sentinel node biopsy to gastric cancer surgery.
AB  - BACKGROUND: Sentinel node (SN) biopsy has been tried in the management of a
      variety of cancers with the hope that it would eliminate many unnecessary lymph
      node dissections, resulting in less morbidity. This important technique, however,
      has not been tried in gastric cancer surgery. The feasibility of SN biopsy and
      its accuracy in predicting the lymph node status in patients with gastric cancer
      were examined in the current study. PATIENTS AND METHODS: SN biopsy was performed
      in patients with T1 (n = 44) or T2 (n = 30) gastric cancers (ie, immediately
      after laparotomy, indocyanine green was injected around the primary tumor, and
      the green-stained nodes [SNs: 2.6 +/- 1.7 nodes per patient] were removed). Then,
      gastrectomy with extended lymphadenectomy was performed. The unstained nodes (non
      SNs: 39 +/- 18 nodes per patient) were obtained from the resected specimens. Both
      SNs and non-SNs were subjected to histologic examination with hematoxylin-eosin.
      RESULTS: SNs could be identified in 73 of 74 patients (success rate, 99%). Of
      these 73 patients, 10 had lymph node metastases in SNs or non-SNs, or both; 6 in
      both SNs and non-SNs; 3 in SNs alone; and 1 in non-SNs alone. The sensitivity of
      the SN status in the diagnosis of the lymph node status of the patient was 90%
      (9/10) and specificity was 100% (63/63). Sensitivity was 100% in the T1 group (n
      = 44) and 88% in the T2 group (n = 29). CONCLUSIONS: SN biopsy using indocyanine
      green can be performed with a high success rate, and the SN status can predict
      the lymph node status with a high degree of accuracy, especially in patients with
      T1 gastric cancer.

PMID- 11231463
TI  - Nitric oxide synthase isoform expression in a porcine model of granulation tissue
      formation.
AB  - BACKGROUND: This study was designed to determine whether the nitric oxide (NO)
      pathway is involved in wound granulation tissue formation. METHODS: A section of
      the pig abdominal wall (excluding the skin) was excised, creating an incisional
      hernia. The resulting defect was repaired with silicone sheeting in a manner that
      mimics a temporary abdominal wall closure. During the 14-day experimental period,
      porcine omentum adhered to the peritoneal edges of the defect and a highly
      vascularized granulation tissue formed on both sides of the sheeting. Granulation
      tissue thickness and wound fluid volume were monitored by ultrasonography and
      epigastric artery flow velocity was monitored by color Doppler flow analysis at
      days 2, 4, 7, 9, 11, and 14. Fluid was serially harvested from the wound
      compartment at days 2, 4, 7, 9, 11, and 14 for nitrite/ nitrate (NOx) analysis.
      Finally, granulation tissue was harvested at day 14 for immunohistochemical and
      molecular analyses. RESULTS: There was a significant increase in granulation
      tissue thickness and wound fluid volume during the 14-day study period. Blood
      flow to the wound increased significantly by day 4 and returned toward baseline
      by day 14. Wound fluid NOx levels significantly increased from days 7 to 11 and
      then decreased to near baseline values by day 14. Wound fluid arginine levels
      significantly decreased when compared with peritoneal fluid and plasma levels at
      day 14, while wound fluid ornithine levels significantly increased.
      Immunohistochemical analysis of granulation tissue at day 14 revealed nitric
      oxide synthase (NOS) 2 was present in the majority of the cells in the
      granulation tissue. NOS 3 was expressed in endothelial cells only, and NOS 1
      expression was not observed in the granulation tissue. CONCLUSIONS: This study
      suggests that NO, NOS 2, and arginine may play critical roles in granulation
      tissue formation and wound healing. Arginase and NOS 2 may compete for available
      arginine as a substrate, thereby limiting later NO production in favor of
      sustained ornithine synthesis.

PMID- 11231464
TI  - Factors larger than 100 kd in post-hemorrhagic shock mesenteric lymph are toxic
      for endothelial cells.
AB  - BACKGROUND: Post-shock mesenteric lymph kills and injures endothelial cells
      (ECs), but neither the mechanism nor the mediators of lymph's toxic effect are
      known. Thus, in these studies we investigated and characterized potential factors
      that may be involved in lymph's toxic effect on ECs. METHODS: Lymph was collected
      hourly from rats before shock, during the shock period, and for 6 hours post
      shock and processed in several ways-including removal of cellular elements,
      freezing, heating, or separation by molecular weight-after which they were tested
      for toxicity (lactate dehydrogenase as a marker of cell injury and trypan blue as
      a marker of cell viability). RESULTS: Controls consisting of medium, pre-shock
      lymph, and post-shock portal vein plasma had no EC toxicity. Lymph collected 1 to
      3 hours post-shock resulted in the death of 90% to 95% of ECs and caused an 8- to
      10-fold increase in lactate dehydrogenase release; however, this toxic effect
      waned by 4 hours post-shock. Endotoxin neutralization and immune cell removal did
      not decrease lymph cytotoxicity but complement inactivation did. By fractionating
      the toxic lymph samples by size, it appears that the putative EC cytotoxic
      mediator(s) is larger than 100,000 d. CONCLUSIONS: Mesenteric lymph collected 1
      to 3 hours after hemorrhagic shock is toxic to ECs, but this effect is lost by 4-
      to 5-hours post-shock and is not dependent on the presence of immune cells or
      endotoxin but does involve complement and other putative mediators of greater
      than 100,000 d.

PMID- 11231465
TI  - Near-infrared spectroscopy reflects changes in mesenteric and systemic perfusion
      during abdominal compartment syndrome.
AB  - BACKGROUND: Continuous and minimally invasive near-infrared spectroscopy (NIRS)
      derived gastric tissue oxygen saturation (GStO(2)) and muscle tissue oxygen
      saturation (MStO(2)) were evaluated in a clinically relevant porcine model of
      hemorrhagic shock and abdominal compartment syndrome (ACS). METHODS:
      Phenobarbital-anesthetized swine underwent pulmonary artery catheter insertion
      for mixed venous oxygen saturation (SvO(2)) measurement and midline laparotomy to
      permit placement of a gastric NIRS probe, a jejunal (regional carbon dioxide
      [PrCO(2)]) tonometer, superior mesenteric artery (SMA) flow probe, and a portal
      vein oxygen saturation (SpvO(2)) catheter. A muscle NIRS probe was placed on the
      front limb. After randomization, Group 1 underwent hemorrhage and resuscitation.
      Group 2 had no hemorrhage or resuscitation. ACS was induced by peritoneal fluid
      infusion in both groups. A significant decrease in SMA flow, SpvO(2), GStO(2),
      SvO(2), and MStO(2) was observed after hemorrhage in Group 1 and with abdominal
      hypertension in both groups. RESULTS: GStO(2) significantly correlated with SMA
      flow (Group 1: r(2) = 0.90; Group 2: r(2) = 0.83) and mesenteric oxygen delivery
      (mesenteric oxygen delivery, Group 1: r(2) = 0.73; Group 2: r(2) = 0.89). MStO(2)
      significantly correlated with SvO(2) (Group 1: r(2) = 0.99; Group 2: r(2) = 0.65)
      and systemic oxygen delivery (SDO2, Group 1: r(2) = 0.60; Group 2: r(2) = 0.88).
      Tonometer-derived PrCO(2) values did not change at any time point in either
      group. CONCLUSIONS: NIRS measurement of GStO(2) and MStO(2) reflected changes in
      mesenteric and systemic perfusion respectively during hemorrhage and ACS.

PMID- 11231466
TI  - M & M with George Block.

PMID- 11231467
TI  - Adrenal hemangioma.

PMID- 11231468
TI  - Anorexia and pancreatitis associated with a gastric duplication cyst of the
      pancreas.

PMID- 11231469
TI  - Polysplenia syndrome and duodenal obstruction.

PMID- 11231470
TI  - Primary pancreatic lymphoma--a diagnosis to remember.

PMID- 11231471
TI  - False recurrence of laparoscopically treated hydatid cysts.

PMID- 11231472
TI  - Mutations of the CYP2C9 gene and the response to warfarin.

PMID- 11231473
TI  - Synchronous occurrence of epithelial and stromal tumors in the stomach.

PMID- 11231475
TI  - Gregor Johann Mendel.

PMID- 11231478
TI  - Primary low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type
      arising in the urinary bladder: report of 4 cases with molecular genetic
      analysis.
AB  - CONTEXT: Primary lymphoma of the urinary bladder is rare. Only 84 cases have been
      reported in the English literature to date, and none of these cases has had
      molecular confirmation of clonal immunoglobulin gene rearrangement. OBJECTIVES:
      To review all cases with primary urinary bladder lymphoma in our records, to
      classify them using the REAL classification, to confirm their immunophenotype and
      genotype, and to determine their outcome. DESIGN: We identified 4 cases of
      primary urinary bladder lymphoma in our medical records from a 30-year period.
      Immunohistochemical detection of immunoglobulin light chains and molecular
      analysis of immunoglobulin heavy-chain genes using the polymerase chain reaction
      were performed on paraffin-embedded material. RESULTS: All patients were older
      than 60 years. The male-female ratio was 1:3. All patients had a history of
      chronic cystitis. Histologic features of mucosa-associated lymphoid tissue
      lymphoma with centrocyte-like cells, plasmacytoid B cells, or both were observed
      in all cases. Monoclonality of B cells was demonstrated by immunohistochemistry,
      polymerase chain reaction, or both methods in every case. All patients presented
      with stage IAE disease, were treated with radiotherapy alone, and have been in
      continuous complete remission for 2 to 13 years. CONCLUSIONS: Primary bladder
      lymphomas are usually of low-grade mucosa-associated lymphoid tissue type. They
      are more common in females and are associated with a history of chronic cystitis.
      Lymphoepithelial lesions are seen only in association with areas of cystitis
      glandularis. B-cell clonality is readily demonstrable by immunohistochemistry
      and/or polymerase chain reaction analysis. Local radiotherapy appears to confer
      long-term control.

PMID- 11231477
TI  - Surgical pathology-based outcomes assessment of breast cancer early diagnosis: a
      College of American Pathologists Q-Probes study in 199 institutions.
AB  - OBJECTIVE: To develop breast cancer outcomes data relating pathologic tumor
      variables at diagnosis with clinical method of detection. DESIGN: Anatomic
      pathologists assessed 30 consecutive breast cancers at each institution,
      resulting in an aggregate database of 4232 breast cancers. SETTING: Hospital
      based laboratories from the United States (98%), Canada, Australia, and Belgium.
      PARTICIPANTS: One hundred ninety-nine laboratories in the 1999 College of
      American Pathologists Q-Probes voluntary quality improvement program. MAIN
      OUTCOME MEASURES: Pathologic variables indicative of favorable outcomes included
      percentage of carcinomas detected at the in situ stage, tumors < or = 1 cm in
      diameter, and invasive cancers with lymph nodes negative for metastases. RESULTS:
      All outcomes measures, including percent in situ carcinomas (26.9% vs 13.8%),
      tumor size < or = 1 cm (57.8% vs 36.5%), and lymph node-negative status (77.8% vs
      64%), were more favorable when tumors were detected by screening mammography (P
      <.001) compared to all other detection methods. CONCLUSIONS: This study
      demonstrates an opportunity for pathologists to develop outcomes information of
      interest to health care organizations, providers, patients, and payers by
      integrating routine oncologic surgical pathology and clinical breast cancer
      detection data. Such readily obtained interim outcomes data trended and
      benchmarked over time can demonstrate the relative clinical efficacy of
      preventive breast care provided by health care systems long before mortality data
      are available.

PMID- 11231479
TI  - Posttransplantation lymphoproliferative disorders in pediatric patients
      undergoing liver transplantation.
AB  - OBJECTIVES: To study the clinicopathologic and molecular genetic findings in
      posttransplantation lymphoproliferative disorders (PTLDs) following pediatric
      liver transplantation and to determine the applicability of a recently proposed
      consensus classification system. DESIGN: The clinical, pathologic, and molecular
      genetic findings of 11 PTLDs that occurred in 10 patients are presented. These 10
      patients were derived from a group of 121 pediatric patients who underwent liver
      transplantation at the University of California, San Francisco. The PTLDs were
      classified using the proposed Society for Hematopathology scheme. Clonality was
      determined by immunohistochemical detection of monotypic immunoglobulin or by
      using polymerase chain reaction-based methods to detect monoclonal immunoglobulin
      heavy-chain gene rearrangements. Epstein-Barr virus (EBV) was detected by
      immunohistochemistry, in situ hybridization, or polymerase chain reaction.
      Epstein-Barr virus typing and the presence of LMP1 gene deletions were also
      analyzed by polymerase chain reaction. RESULTS: There were 3 early lesions, 4
      polymorphic PTLDs, and 4 monomorphic PTLDs. Monoclonality was demonstrated in 8
      of 9 cases assessed. Epstein-Barr virus was present in all cases; of 9 cases
      assessed by polymerase chain reaction, the virus was type A in 8 and type B in 1.
      No EBV LMP1 gene deletions were identified. The corresponding liver explants were
      negative for EBV in 8 cases and positive in 1 case. Greater than 3 foci of
      disease and monomorphic PTLD were associated with decreased actuarial survival (P
      <.05). CONCLUSIONS: The prognosis of pediatric patients with PTLD is favorable
      for early lesions and polymorphous PTLD, particularly in patients with localized
      disease. Multifocal disease and monomorphic PTLD are associated with an
      unfavorable prognosis.

PMID- 11231480
TI  - Evaluation of the Candigen enzyme-linked immunosorbent assay for quantitative
      detection of Candida species antigen.
AB  - OBJECTIVE: To assess the clinical utility of an enzyme-linked immunosorbent assay
      method for the quantitative detection of Candida species antigen (Candigen;
      Biomerica Inc, Newport Beach, Calif) in patients with suspected disseminated
      candidiasis. METHODS: Specimens of blood or cerebrospinal fluid from 75 patients
      with suspected disseminated candidiasis were analyzed by the Candigen test.
      Results were compared with those obtained by culture and polymerase chain
      reaction (PCR) analysis. RESULTS: Thirty-seven patients had specimens positive
      for Candida species by either culture or PCR. Of these specimens, 4 were positive
      by both culture and PCR, 21 were culture positive but PCR negative, and 12 were
      PCR positive but culture negative. Five specimens were positive by the Candigen
      test, all of which were PCR positive but culture negative. The sensitivity,
      specificity, and positive and negative predictive values of the Candigen test
      compared to culture plus PCR were 13.5%, 100%, 100%, and 54.3%, respectively.
      Turnaround time for the Candigen test was approximately 3 hours. CONCLUSION: The
      Candigen test showed excellent specificity and turnaround time, but its poor
      sensitivity coupled with its inability to provide species information or
      susceptibility data make its clinical utility questionable.

PMID- 11231481
TI  - Novel method for simultaneous analysis of p53 and K-ras mutations and p53 protein
      expression in single histologic sections.
AB  - BACKGROUND AND OBJECTIVE: Abnormal protein expression and gene mutation should be
      examined on exactly identified lesions. To perform simultaneous analyses of
      oncogene or tumor suppressor gene mutations and related protein expression in
      single histologic sections, we have developed a novel method using an antigen
      retrieval solution for a polymerase chain reaction template before
      immunohistochemical staining. METHODS: Using 20 cases of sporadic colorectal
      carcinoma, several kinds of antigen-retrieval solutions were tested after heating
      rehydrated, 4-microm-thick, formalin-fixed, paraffin-embedded histologic sections
      at 96 degrees C for 20 minutes. Polymerase chain reaction-single-strand
      conformation polymorphism analysis was conducted for p53 (exons 5 through 9) and
      K-ras (exons 1 and 2), and the histologic sections were then immunostained with
      monoclonal antibody against p53. RESULTS: DNA analysis of antigen-retrieval
      solutions was possible in all 20 cases and revealed completely consistent results
      (100%) with fresh cancer tissue and microdissected cancer tissue of paraffin
      embedded histologic sections. With this method, K-ras mutations were positive in
      10 of 20 cases (exon 1 in 9 cases and exon 2 in 1 case) and p53 mutations were
      positive in 9 of 20 cases (exon 5 in 4 cases, exon 6 in 1, exon 7 in 3, and exon
      8 in 1 case), with 8 of the 9 p53 mutation cases showing diffuse p53 protein
      expression on immunostaining. Base alterations of all abnormal conformers were
      confirmed with direct sequencing. For polymerase chain reaction-single-strand
      conformation polymorphism analysis, sodium citrate buffer (pH 6.0) was found to
      be the optimal antigen-retrieval solution. CONCLUSIONS: This newly developed
      method can be used for routine immunostaining and genetic analysis with single
      histologic sections.

PMID- 11231482
TI  - Detection of human papillomavirus on Papanicolaou-stained cervical smears using
      indirect in situ polymerase chain reaction hybridization.
AB  - OBJECTIVE: Polymerase chain reaction (PCR) and indirect in situ hybridization
      were combined to detect human papillomavirus (HPV) DNA on Papanicolaou (PAP)
      stained cervical smears. To our knowledge, this is the first report of an
      experiment using indirect in situ PCR (IS-PCR) on PAP-stained cervical smears.
      DESIGN: We collected native cell specimens from cervicovaginal lavage of 162
      patients with squamous intraepithelial lesions. Solution-phase PCR (SP-PCR) was
      performed as the reference method in the detection of HPV DNA. Indirect IS-PCR
      was carried out for the same patients to detect the HPV DNA types 6/11 and 16/18
      after the PAP-stained smears had been decolorized. Low-risk and high-risk HPV DNA
      types were also detected by both SP-PCR and indirect IS-PCR. RESULTS: In the
      evaluation by indirect IS-PCR, 48 of 81 PAP-stained cell smears of low-grade
      squamous intraepithelial lesions were positive for HPV DNA, as compared to 40
      positive cell smears determined by indirect SP-PCR (sensitivity of indirect IS
      PCR compared to SP-PCR, 98.1%). Forty-two of 42 high-grade squamous
      intraepithelial lesion samples were positive for HPV DNA, as determined by both
      methods (sensitivity of IS-PCR, 100%). Cell lines investigated in this study as
      positive or negative controls for HPV DNA were confirmed by indirect IS-PCR and
      SP-PCR. CONCLUSIONS: Our data show that in comparison to SP-PCR, indirect IS-PCR
      is a highly sensitive method to detect HPV DNA in cell smears from the uterine
      cervix. The advantages of indirect IS-PCR are (a) low numbers of cells needed,
      (b) the possibility of using PAP-stained specimens, and (c) cytologic details of
      smears can be preserved.

PMID- 11231483
TI  - Verumontanum mucosal gland hyperplasia is associated with atypical adenomatous
      hyperplasia of the prostate.
AB  - BACKGROUND: Verumontanum mucosal gland hyperplasia (VMGH) and atypical
      adenomatous hyperplasia (AAH) are both small glandular proliferations that are
      histologically and topographically unique. METHODS: One hundred ten randomly
      selected, whole-mount, radical prostatectomy specimens were reviewed to assess
      independently the normal histology of the prostatic urethra and periurethral area
      and the association of AAH with other pathologic features, including VMGH. The
      degree of nodular hyperplasia was evaluated by total prostate weight for
      comparison purposes. RESULTS: Atypical adenomatous hyperplasia was found in 37
      cases (33.6%) and was nearly always (32/37) associated with nodules of nodular
      hyperplasia. Verumontanum mucosal gland hyperplasia was present in 32 cases
      (29.1%; 21 with AAH, 11 without AAH). There was a significant association between
      presence of VMGH and AAH (P <.001, Fisher exact test). The degree of nodular
      hyperplasia was not significantly different between prostates with and without
      VMGH or AAH. CONCLUSIONS: These results suggest that AAH and VMGH occur more
      commonly in prostates when the other is also present.

PMID- 11231484
TI  - Absence of Epstein-Barr virus in smooth muscle cells of idiopathic hypertrophic
      pyloric stenosis.
AB  - CONTEXT: The etiology of idiopathic hypertrophic pyloric stenosis (IHPS) is
      unknown. Epstein-Barr virus (EBV) infects smooth muscle cells and is associated
      with leiomyomas and leiomyosarcomas of immunocompromised persons, including
      persons with the acquired immunodeficiency syndrome. OBJECTIVE: To determine
      whether EBV is causally associated with IHPS. DESIGN: Biopsy samples of the
      pylorus were obtained from 10 infants with projectile vomiting and pyloric
      hypertrophy on ultrasound, with confirmation of hypertrophy at the time of
      pyloromyotomy. The presence of EBV infection was tested by in situ hybridization
      for EBV-encoded RNA 1 (EBER1) in smooth muscle cells of IHPS. SETTING: Biopsy
      specimens were obtained from children treated for IHPS at a tertiary referral
      hospital and were tested in a clinical molecular diagnostics laboratory. RESULTS:
      All of the 10 smooth muscle biopsies were negative for EBER1. Cellular U6 RNA was
      detected in all smooth muscle samples, confirming that the RNA in the specimens
      was intact and capable of detection by in situ hybridization. CONCLUSIONS: The
      absence of EBER1 in 10 cases of clinically diagnosed and histopathologically
      confirmed cases of IHPS effectively excludes EBV infection of smooth muscle cells
      as a causal factor in the pathogenesis of IHPS.

PMID- 11231485
TI  - Two-color, cytokeratin-labeled dna flow cytometric analysis of 332 breast
      cancers: lack of prognostic value with 12-year follow-up.
AB  - CONTEXT: DNA flow cytometry of breast cancer is a proposed tumor marker of
      prognostic significance that is of controversial clinical utility because of lack
      of standardization and confirmatory studies. OBJECTIVE: To evaluate the
      prognostic significance of the more informative technique of multiparametric 2
      color DNA flow cytometry as recommended by the 1992 DNA Cytometry Consensus
      Conference. DESIGN: Three hundred thirty-two breast carcinomas with 7 to 12 years
      of follow-up were prospectively analyzed as fresh tumors that were mechanically
      dissociated into whole cell suspensions. These suspensions were dual fluorescence
      labeled with propidium iodide (DNA) and antibodies to cytokeratin (epithelium)
      and leukocyte common antigen (internal leukocyte control) for gated analysis of
      subpopulations. Multicycle software with histogram-dependent algorithms employing
      background, aggregate, and debris correction were used in DNA and cell-cycle
      quantitation. Data were analyzed according to the DNA Flow Cytometry Consensus
      Conference recommendations. RESULTS: DNA ploidy and proliferation stratified into
      3 categories were not predictive of overall or disease-free survival. Sixty-five
      percent of tumors were nondiploid, and 35.4% were diploid. Two hundred six tumors
      were able to be evaluated for synthesis-phase fraction (SPF) analysis, with 74 of
      206 cases in the low range (<13.4%), 36.4% in the intermediate range (>13.5 to
      <25.4%), and 27.6% in the high SPF (>25.5%) category. Aneuploid tumors tended to
      have a higher SPF. Univariate survival analysis showed prognostic significance of
      the following: tumor size, stage, TNM components, vascular invasion, nuclear
      grade, and histologic grade. Only T classification, presence of positive axillary
      lymph nodes, and distant metastases were significant independent predictors of
      survival in multivariate Cox regression models. Age and hormone receptor status
      showed no prognostic significance. Synthesis-phase fraction was significantly
      correlated with tumor size, stage, T classification, nuclear and histologic
      grade, presence of estrogen or progesterone receptors, and axillary lymph node
      status. None of the histologic parameters showed any significant association with
      DNA aneuploidy, except for high nuclear and histologic grade and the absence of
      estrogen receptors. CONCLUSIONS: Despite the use of state-of-the-art processing
      and flow cytometry analytic techniques, DNA ploidy and proliferation measurements
      were not predictive of survival in any stage of breast cancer. However, select
      histopathologic parameters and TNM stage were significant predictors of survival
      in univariate and multivariate analyses. We conclude that DNA ploidy and
      proliferation measurements do not provide significant prognostic information for
      clinicians to integrate into therapeutic decision making for patients with breast
      cancer.

PMID- 11231486
TI  - Histologic features of zygomycosis: emphasis on perineural invasion and fungal
      morphology.
AB  - OBJECTIVE: Invasive zygomycosis is rapidly progressive and is associated with
      angioinvasion and infarction. Invasive disease requires emergent surgical and
      medical intervention. Because it is important for surgical pathologists to
      recognize these fungi and their preferential sites of growth, the objective of
      this article is to describe the fungal morphology and histopathologic findings in
      biopsies from patients with zygomycotic disease, with emphasis on preferential
      sites of fungal growth. DESIGN: Medical record and histologic review identified
      20 patients with zygomycosis. Inclusion criteria included the presence of typical
      ribbonlike hyphae and positive culture, a clinical history of invasive
      zygomycosis, or both. The histologic features of disease and the fungal
      morphology were assessed. RESULTS: Fungus ball (15%), rhinocerebral (55%), and
      pulmonary (30%) disease were the types of disease represented. The inflammatory
      responses were predominantly neutrophilic (50%), predominantly granulomatous
      (5%), pyogranulomatous (25%), or absent (20%). Invasive disease was characterized
      by prominent infarcts (94%), angioinvasion (100%), and, surprisingly, prominent
      perineural invasion (90%) in biopsies that contained nerves for evaluation. At
      least rare hyphal septa were always seen (100%), and most branches (95%) varied
      from 45 degrees to 90 degrees. CONCLUSIONS: As known to mycologists, zygomycetes
      are pauciseptate, rather than aseptate, molds. Therefore, the presence of an
      occasional septum is expected. Perineural invasion is a common finding in
      invasive zygomycosis, as are angioinvasion and infarcts. Therefore, prior to
      excluding the presence of these fungi in biopsies suspected to contain
      zygomycetes, the perineural space should be carefully examined.

PMID- 11231487
TI  - Splenic inflammatory myofibroblastic tumor (inflammatory pseudotumor): a
      clinicopathologic and immunophenotypic study of 12 cases.
AB  - CONTEXT: Inflammatory pseudotumor is an uncommon and enigmatic lesion. The
      spindle cells found in this tumor have features of myofibroblasts. Because of the
      indefinite relationship of these lesions with inflammatory fibrosarcoma and their
      indefinite biologic behavior, inflammatory pseudotumor is currently classified as
      inflammatory myofibroblastic tumor (IMT). To date, only case reports or small
      series have been published on these tumors, which are primary in the spleen.
      DESIGN: In this study, we describe the clinical, morphologic, and
      immunophenotypic findings of 12 cases of splenic IMT and examine their
      relationship to Epstein-Barr virus (EBV). RESULTS: The patients included 8 women
      and 3 men, ranging from 19 to 77 years of age (mean, 53 years; median, 60 years).
      Demographic data were unavailable for 1 patient. Patients generally presented
      with abdominal pain (n = 5) and fever (n = 4). Associated lesions included renal
      cell carcinoma (n = 2), colonic adenocarcinoma (n = 1), and cholecystitis (n =
      1). All tumors were composed of a bland spindle cell proliferation in association
      with a variable mixed inflammatory component. There were 2 growth patterns,
      namely, a cellular spindle cell pattern and a hypocellular fibrous pattern. An
      immunohistochemical panel confirmed the myofibroblastic nature of the spindle
      cells. The spindle cells of 2 cases were immunoreactive for EBV latent membrane
      protein 1, whereas 6 of 10 cases were positive for EBV-encoded RNA using in situ
      hybridization. Follow-up was available for 8 patients; 6 were alive with no
      evidence of recurrence and 2 were dead of other causes. CONCLUSION: Splenic IMTs
      are uncommon lesions that can be distinguished from other conditions using a
      combination of clinical, histologic, and immunophenotypic findings. Epstein-Barr
      virus may play a role in the pathogenesis of splenic IMT, and there may be an
      association of splenic IMT with concomitant disease or malignancy. Most splenic
      IMTs have an excellent long-term prognosis.

PMID- 11231488
TI  - Goblet cell carcinoids of the appendix: immunophenotype and ultrastructural
      study.
AB  - BACKGROUND: Goblet cell carcinoids of the appendix are rare neoplasms with
      uncertain biological behavior. OBJECTIVE: The aims of our study were to evaluate
      the immunophenotype of this neoplasm with cell cycle/cell proliferation markers
      and to understand their histogenesis with ultrastructural analysis using
      conventional carcinoids as a frame of reference. METHODS: Clinical data and
      archival pathologic material of all goblet cell carcinoids of the appendix
      recorded by the Saskatchewan Cancer Registry between 1970 and 1998 were reviewed
      and evaluated by light microscopy, histochemistry, immunohistochemistry, and
      electron microscopy. RESULTS: Seven cases of goblet cell carcinoids were
      identified among 110 cases of conventional carcinoids of the appendix.
      Histopathology revealed widespread infiltration of the periappendiceal fat in all
      cases, with extensive perineural invasion. The cells stained strongly positive
      for mucicarmine, periodic acid-Schiff, periodic acid-Schiff diastase, Alcian
      blue, cytokeratin, and carcinoembryonic antigen. Most cases were positive for
      synaptophysin. Increased expression of cell proliferation markers and cell cycle
      markers was observed. Expression of p53 was strong in one case. Electron
      microscopy demonstrated the presence of mucinous vacuoles of varying sizes and
      occasional membrane-bound neuroendocrine granules. CONCLUSIONS: Goblet cell
      carcinoids of the appendix arise from a pluripotent cell with divergent
      neuroendocrine and mucinous differentiation. These neoplasms are widely invasive;
      they demonstrate a high cellular proliferation rate and dysregulation of the cell
      cycle with up-regulation of cyclin D1 and p21, and down-regulation of p16.
      Complete removal of the tumor is recommended because of the unpredictable
      biological behavior of this tumor, which includes delayed local recurrences and
      lung metastases.

PMID- 11231489
TI  - The new hematology analyzer Sysmex XE-2100: performance evaluation of a novel
      white blood cell differential technology.
AB  - CONTEXT: The new hematology analyzer Sysmex XE-2100 (TOA Medical Electronics,
      Kobe, Japan) has a novel, combined, white blood cell differential technology and
      a special reagent system to enumerate nucleated red blood cells. DESIGN:
      Performance evaluation of both technologies of the Sysmex XE-2100 according to
      the H20-A protocol of the National Committee for Clinical and Laboratory
      Standards and comparison of the results with those for the hematology analyzer
      Sysmex NE-8000 (TOA Medical Electronics). SPECIMENS: Five hundred forty-four
      blood samples randomly chosen from various inpatient and outpatient departments
      of the Vienna University hospital. RESULTS: Five-part white blood cell
      differential counts on the XE-2100 revealed excellent correlation with the manual
      reference method for neutrophils, lymphocytes, and eosinophils (r =.925,.922,
      and.877, respectively) and good correlation for monocytes and basophils (r =.756
      and.763, respectively). The efficiency rates of flagging for the presence of
      >/=1% abnormal white blood cells were 83% (XE-2100) and 66% (NE-8000). The
      correlation of automated and microscopic nucleated red blood cell counts was
      excellent (r =.97). CONCLUSIONS: From the present evaluation and our former
      experience with other types of Sysmex analyzers, we conclude that the new white
      blood cell differential technology of the XE-2100 represents a further
      development toward more efficient flagging of abnormal white blood cells.

PMID- 11231490
TI  - Primitive neuroectodermal tumor of the lung.
AB  - Primitive neuroectodermal tumors occur most frequently in bone and soft tissue
      but have been reported in other locations. Primary lung primitive neuroectodermal
      tumors without pleural or chest wall involvement are extremely rare. We present a
      case with immunohistochemical and ultrastructural studies and follow-up of the
      patient. An 18-year-old man presented with hemoptysis. Chest radiographs revealed
      a right middle lobe mass, and bronchoscopy showed an endobronchial tumor. The
      lesion was resected by middle lobectomy. After 2 years, a local recurrence was
      treated by pneumonectomy. The patient died after surgery. Histologically, the
      tumor was composed of uniform cells with round nuclei and scanty cytoplasm
      arranged in cohesive lobules with occasional rosette formation.
      Immunohistochemically, the tumor was positive for vimentin, CD99, neuron-specific
      enolase, and neurofilaments. Ultrastructural study revealed neurosecretory
      granules and cytoplasmic processes. Our case shows the value of
      immunohistochemistry and electron microscopy in the diagnosis of primitive
      neuroectodermal tumors in unusual locations.

PMID- 11231491
TI  - Nasal chondromesenchymal hamartoma in children: report of 2 cases with review of
      the literature.
AB  - Hamartoma in the nasal cavity of children is especially rare. Most documented
      cases occurred in infants, with characteristic histologic features of a mixture
      of various mesenchymal tissues. McDermott et al designated it nasal
      chondromesenchymal hamartoma in 1998, and it has since been considered a distinct
      clinicopathological entity. We report 2 such examples in a full-term male newborn
      and a 9-month-old boy, respectively. Histologically, both cases were
      characterized by a mixture of various mesenchymal elements, including spindle
      cells, collagen fibers, and irregular islands of osseous and chondroid tissue.
      Immunohistochemical study showed positivity to vimentin and S100 protein.
      Ultrastructural examination of case 1 demonstrated fibroblastic and
      myofibroblastic differentiation in tumor cells. There were 11 cases of nasal
      chondromesenchymal hamartoma in children published to date. The tumor has a
      benign biological behavior, and complete resection is the treatment of choice. It
      is apt to be misdiagnosed because of overlapping histologic features shared with
      a number of benign and malignant soft tissue tumors. Awareness of this entity is
      essential for correct diagnosis and adequate therapy.

PMID- 11231492
TI  - Low triglyceride levels affect calculation of low-density lipoprotein cholesterol
      values.
AB  - The Friedewald formula for the calculation of low-density lipoprotein cholesterol
      (LDL-C) values is fairly accurate provided the triglyceride value is less than
      400 mg/dL. It is not clear whether the estimation is also valid in the presence
      of low triglyceride and high cholesterol levels. We describe herein a patient
      with a low triglyceride value of approximately 50 mg/dL, a high cholesterol
      level, and a discrepant LDL-C level. The LDL-C level using the Friedewald
      calculation turned out to be much higher than the LDL-C level using direct
      measurement. We, therefore, suggest that in the presence of low triglyceride and
      high cholesterol levels, the LDL-C level should be measured directly instead of
      using the Friedewald calculation.

PMID- 11231493
TI  - Malignant solitary fibrous tumor of the pleura with liposarcomatous
      differentiation.
AB  - Pleural solitary fibrous tumors (SFTs) are uncommon tumors. Although these tumors
      have been well characterized, malignant pleural SFTs with liposarcomatous
      differentiation have not been reported. We report an unusual malignant pleural
      SFT intermixed with foci of well-differentiated liposarcoma. The patient was a 66
      year-old, white man with a large, solid right pleural mass that measured 13.5 x
      10.3 x 8.5 cm. The tumor was composed of spindle-shaped and plump cells embedded
      in dense collagenous stroma. The tumor cells were arranged in interlacing
      fascicles or in a patternless pattern. Marked nuclear atypia, a high mitotic rate
      (21 mitoses per 10 high-power fields), and areas of prominent necrosis were
      evident. In addition, numerous adipocytes mixed with typical lipoblasts were seen
      scattered throughout portions of the tumor. Immunohistochemistry revealed the
      tumor cells were strongly positive for CD34 and vimentin and negative for
      cytokeratin, desmin, smooth muscle actin (IA4), and S100. To the best of our
      knowledge, this case represents the first example of a malignant SFT with
      liposarcomatous differentiation.

PMID- 11231494
TI  - Primary liposarcoma of the liver: a case report and review of literature.
AB  - Liposarcoma is a rare mesenchymal malignant tumor, which usually originates in
      the retroperitoneum and the extremities. Seven cases of primary liposarcoma of
      the liver have been previously reported. We present the eighth case, which
      occurred in an adult female patient. Primary liposarcoma of the liver, although
      extremely rare, must be considered in the differential diagnosis of a hepatic
      mass that develops in a noncirrhotic liver, especially in patients who are
      potential candidates for orthotopic liver transplantation. Liposarcoma is an
      absolute contraindication for liver transplantation.

PMID- 11231495
TI  - Natural killer cell precursor acute lymphoma/leukemia presenting in an infant.
AB  - Lymphoma/leukemia derived from immature natural killer (NK) cells occur most
      commonly in adults and are characterized by blastic cytologic features and an
      aggressive outcome. Predilection for extranodal sites and absence of the Epstein
      Barr virus associated with mature NK cell malignancies further distinguish this
      entity. We present a NK precursor acute lymphoma presenting with multiple masses
      in an infant without circulating blasts or marrow replacement by disease. The
      diagnostic difficulty arose from several factors, including young age,
      presentation with multiple masses, blastic cytologic features mistaken for a
      small, round, blue cell tumor, and the absence of lineage-specific markers. The
      CD56+, CD34+, CD33+, MPO-, cytoplasmic CD3+, CD45-, CD7-, HLA-DR-, and TdT-
      immunophenotype of this neoplasm overlaps with previously reported cases of
      myeloid/NK precursor acute leukemia and blastic NK cell lymphoma/leukemia. This
      case emphasizes the need for a strong index of suspicion to recognize this rare
      entity and to distinguish it from solid tumors and other hematolymphoid neoplasms
      that occur in infancy.

PMID- 11231496
TI  - Pleural posttransplantation lymphoproliferative disorder following liver
      transplantation.
AB  - A case of posttransplantation lymphoproliferative disorder (PTLD) involving the
      pleura is reported. The patient was a 57-year-old man who underwent liver
      transplantation 2 years prior to the development of PTLD. The PTLD was pleural
      based and was first detected by radiologic studies as a pleural effusion.
      Transbronchial biopsy and cytologic examination of 2 pleural fluid specimens were
      nondiagnostic. Subsequent open-wedge biopsy revealed a monomorphic PTLD, composed
      of large immunoblasts with plasmacytoid differentiation. Immunohistochemical
      studies demonstrated B-cell lineage with expression of monotypic cytoplasmic
      immunoglobulin kappa light chain and CD79a, and absence of T-cell antigens.
      Immunohistochemical and in situ hybridization studies demonstrated Epstein-Barr
      virus protein and RNA, respectively. No evidence of human herpesvirus 8 DNA was
      detected by polymerase chain reaction. We report this case because pleural-based
      PTLD is rare. The diagnosis of this entity is made more difficult by the fact
      that PTLD is often underrepresented in pleural fluid cytology samples.

PMID- 11231497
TI  - Primary Epstein-Barr virus-associated Hodgkin disease of the ileum complicating
      Crohn disease.
AB  - We describe a case of primary Hodgkin disease of the terminal ileum in a 38-year
      old man with Crohn disease of 24 years' duration. The infiltrate was located in
      an ulcerated fistula involving the terminal ileum and urinary bladder. Reed
      Sternberg cells and their variants were characteristically positive for CD15,
      fascin, and CD30 and showed focal positivity for CD20. Epstein-Barr virus
      messenger RNA was also detected in the neoplastic cells. Staging revealed no
      evidence of other lymph node or organ involvement. Although rare, primary
      gastrointestinal Hodgkin disease arising in the setting of Crohn disease may have
      a stronger association with Epstein-Barr virus infection than conventional
      Hodgkin disease.

PMID- 11231498
TI  - Primary paratesticular lymphoma: a report of 2 cases and review of literature.
AB  - Non-Hodgkin lymphoma arising in the paratesticular organs without testicular
      involvement is rare. In most previously reported cases, the classification
      systems that were used are now outdated and/or immunologic studies were not done.
      We report the clinical and pathologic features of 2 cases of non-Hodgkin lymphoma
      arising in the epididymis and the spermatic cord. Patient 1 was a 35-year-old man
      who presented with a painless scrotal mass. Patient 2 was a 61-year-old man who
      presented with a right inguinal mass. Orchiectomy performed in both patients
      revealed a mass confined to the epididymis in patient 1 and to the spermatic cord
      in patient 2. Histologic examination in both cases revealed diffuse large cell
      lymphoma, and immunohistochemical studies supported B-cell lineage. Subsequent
      staging studies showed no other site of disease in patient 1 and an isolated mass
      anterior to the right psoas muscle in patient 2. Malignant lymphoma involving
      testicular adnexal structures without involvement of the testis is extremely
      uncommon. To our knowledge, only 6 cases confined to the epididymis and 12 cases
      confined to the spermatic cord have been reported previously.

PMID- 11231499
TI  - Carcinosarcoma of the tongue with cyclin D1 gene amplification.
AB  - Carcinosarcoma of the tongue is a rare malignancy and its molecular aspect is
      unclear. A case of carcinosarcoma of the tongue in a 51-year-old man is
      presented. A polypoid tumor of the tongue, measuring 12 x 12 x 6 mm, was
      resected. Histologically, the tumor was composed of a squamous cell carcinoma and
      a spindle cell sarcomatous component. We previously showed that one cell-cycle
      regulator, the cyclin D1 gene, was frequently amplified in esophageal
      carcinosarcoma, which shows the same morphologic features as carcinosarcoma of
      the tongue. In this case, we examined whether the cyclin D1 gene is amplified in
      carcinosarcoma of the tongue as well. Fluorescence in situ hybridization analysis
      revealed that the cyclin D1 gene was amplified in both components of
      carcinosarcoma of the tongue. The cyclin D1 protein was also detected by
      immunostaining in both components. Our results suggest that the amplification of
      cyclin D1 gene plays a role in the molecular pathogenesis of carcinosarcoma of
      the tongue, at least in some cases.

PMID- 11231500
TI  - A unique, complex variant philadelphia chromosome translocation in a patient with
      typical chronic myelogenous leukemia.
AB  - The Philadelphia (Ph) chromosome [der(22) t(9;22)(q34;q11)] is the characteristic
      chromosomal abnormality found in chronic myelogenous leukemia (CML). This
      chromosome has been reported in patients with other chromosomal abnormalities. In
      this study, we describe a patient with hematologically typical chronic-phase CML
      with an unusual and complex translocation involving chromosomes 9, 11, and 22.
      These complex translocations were identified by G-banded conventional
      cytogenetics and confirmed by fluorescence in situ hybridization (FISH) using
      whole chromosome painting probes (wcp). To the best of our knowledge, these are
      unique translocations involving the short and the long arms of chromosome 9 in 4
      different translocations with the short arm of chromosome 11 and the long arm of
      chromosome 22.

PMID- 11231501
TI  - High-grade prostatic intraepithelial neoplasia: a study of pathologists'
      responses in the College of American Pathologists Performance Improvement Program
      in Diagnostic Surgical Pathology.

PMID- 11231502
TI  - Pathologic quiz case. A large mesentric mass in 40-year-old man.

PMID- 11231503
TI  - Pathologic quiz case. Abdominal mass in a neonate.

PMID- 11231504
TI  - Pathologic quiz case. Retroperitoneal soft tissue mass presenting with acute
      renal failure.

PMID- 11231505
TI  - Pathologic quiz case. Unremitting ulcer in a scuba diver.

PMID- 11231506
TI  - Botfly infestation (Dermatobia hominis).

PMID- 11231507
TI  - Vascular invasion by hepatocellular carcinoma.

PMID- 11231513
TI  - A cold dose of medicine.

PMID- 11231515
TI  - US Presidential transition prompts biotech policy frenzy.

PMID- 11231516
TI  - Biotech industry faces new bottleneck.

PMID- 11231517
TI  - Curagen sets precedent in post genomics era.

PMID- 11231518
TI  - Nasdaq restructures biotech index.

PMID- 11231519
TI  - Amgen preserves erythropoietin monopoly for now.

PMID- 11231520
TI  - Value of rice genome still in the husk.

PMID- 11231521
TI  - Japan launches rice genome simulator.

PMID- 11231538
TI  - Genomics and human life span-what's left to extend?

PMID- 11231539
TI  - Piecing together the significance of splicing.

PMID- 11231540
TI  - Bioethics for an educated debate.

PMID- 11231541
TI  - Bt toxin uptake from soil by plants.

PMID- 11231542
TI  - Regenerative medicine.

PMID- 11231543
TI  - The end of the beginning for genomic medicine.

PMID- 11231544
TI  - Mapping a role for SNPs in drug development.

PMID- 11231545
TI  - Integrated antifungal drug discovery in Candida albicans.

PMID- 11231546
TI  - Getting sense and finding function in protozoa.

PMID- 11231547
TI  - A rapid coming of age in tree biotechnology.

PMID- 11231553
TI  - Telomerized human microvasculature is functional in vivo.
AB  - Previously we showed the superior in vitro survival of human telomerase reverse
      transcriptase (hTERT)-transduced human endothelial cells (EC). Here we show that
      retroviral-mediated transduction of hTERT in human dermal microvascular EC
      (HDMEC) results in cell lines that form microvascular structures when
      subcutaneously implanted in severe combined immunodeficiency (SCID) mice. Anti
      human type IV collagen basement membrane immunoreactivity and visualization of
      enhanced green fluorescent protein (eGFP)-labeled microvessels confirmed the
      human origin of these capillaries. No human vasculature was observed after
      implantation of HT1080 fibrosarcoma cells, 293 human embryonic kidney cells, or
      human skin fibroblasts. Intravascular red fluorescent microspheres injected into
      host circulation were found within green "telomerized" microvessels, indicating
      functional murine-human vessel anastamoses. Whereas primary HDMEC-derived vessel
      density decreased with time, telomerized HDMEC maintained durable vessels six
      weeks after xenografting. Modulation of implant vessel density by exposure to
      different angiogenic and angiostatic factors demonstrated the utility of this
      system for the study of human microvascular remodeling in vivo.

PMID- 11231554
TI  - Filovirus-pseudotyped lentiviral vector can efficiently and stably transduce
      airway epithelia in vivo.
AB  - Traditional gene therapy vectors have demonstrated limited utility for treatment
      of chronic lung diseases such as cystic fibrosis (CF). Herein we describe a
      vector based on a Filovirus envelope protein-pseudotyped HIV vector, which we
      chose after systematically evaluating multiple strategies. The vector efficiently
      transduces intact airway epithelium from the apical surface, as demonstrated in
      both in vitro and in vivo model systems. This shows the potential of pseudotyping
      in expanding the utility of lentiviral vectors. Pseudotyped lentiviral vectors
      may hold promise for the treatment of CF.

PMID- 11231555
TI  - Inhibition of gene expression in Entamoeba histolytica with antisense peptide
      nucleic acid oligomers.
AB  - Peptide nucleic acids (PNAs) may be a potent tool for gene function studies in
      medically important parasitic organisms, especially those that have not before
      been accessible to molecular genetic knockout approaches. One such organism is
      Entamoeba histolytica, the causative agent of amebiasis, which infects about 500
      million people and is the cause of clinical disease in over 40 million each year,
      mainly in the tropical and subtropical world. We used PNA antisense oligomers to
      inhibit expression of an episomally expressed gene (neomycin
      phosphorotransferase, NPT) and a chromosomal gene (EhErd2, a homolog of Erd2, a
      marker of the Golgi system in eukaryotic cells) in axenically cultured
      trophozoites of E. histolytica. Measurement of NPT enzyme activity and EhErd2
      protein levels, as well as measurement of cellular proliferation, revealed
      specific decreases in expression of the target genes, and concomitant inhibition
      of cell growth, in trophozoites treated with micromolar concentrations of
      unmodified antisense PNA oligomers.

PMID- 11231556
TI  - An antisense-based functional genomics approach for identification of genes
      critical for growth of Candida albicans.
AB  - Converting the complete genome sequence of Candida albicans into meaningful
      biological information will require comprehensive screens for identifying
      functional classes of genes. Most systems described so far are not applicable to
      C. albicans because of its difficulty with mating, its diploid nature, and the
      lack of functional random insertional mutagenesis methods. We examined artificial
      gene suppression as a means to identify gene products critical for growth of this
      pathogen; these represent new antifungal drug targets. To achieve gene
      suppression we combined antisense RNA inhibition and promoter interference. After
      cloning antisense complementary DNA (cDNA) fragments under control of an
      inducible GAL1 promoter, we transferred the resulting libraries to C. albicans.
      Over 2,000 transformant colonies were screened for a promoter-induced diminished
      growth phenotype. After recovery of the plasmids, sequence determination of their
      inserts revealed the messenger RNA (mRNA) they inhibited or the gene they
      disrupted. Eighty-six genes critical for growth were identified, 45 with unknown
      function. When used in high-throughput screening for antifungals, the crippled C.
      albicans strains generated in this study showed enhanced sensitivity to specific
      drugs.

PMID- 11231557
TI  - Large-scale analysis of the yeast proteome by multidimensional protein
      identification technology.
AB  - We describe a largely unbiased method for rapid and large-scale proteome analysis
      by multidimensional liquid chromatography, tandem mass spectrometry, and database
      searching by the SEQUEST algorithm, named multidimensional protein identification
      technology (MudPIT). MudPIT was applied to the proteome of the Saccharomyces
      cerevisiae strain BJ5460 grown to mid-log phase and yielded the largest proteome
      analysis to date. A total of 1,484 proteins were detected and identified.
      Categorization of these hits demonstrated the ability of this technology to
      detect and identify proteins rarely seen in proteome analysis, including low
      abundance proteins like transcription factors and protein kinases. Furthermore,
      we identified 131 proteins with three or more predicted transmembrane domains,
      which allowed us to map the soluble domains of many of the integral membrane
      proteins. MudPIT is useful for proteome analysis and may be specifically applied
      to integral membrane proteins to obtain detailed biochemical information on this
      unwieldy class of proteins.

PMID- 11231558
TI  - Rapid discrimination among individual DNA hairpin molecules at single-nucleotide
      resolution using an ion channel.
AB  - RNA and DNA strands produce ionic current signatures when driven through an alpha
      hemolysin channel by an applied voltage. Here we combine this nanopore detector
      with a support vector machine (SVM) to analyze DNA hairpin molecules on the
      millisecond time scale. Measurable properties include duplex stem length, base
      pair mismatches, and loop length. This nanopore instrument can discriminate
      between individual DNA hairpins that differ by one base pair or by one
      nucleotide.

PMID- 11231559
TI  - Detection of single-base DNA mutations by enzyme-amplified electronic
      transduction.
AB  - Here we describe a method for the sensitive detection of a single-base mutation
      in DNA. We assembled a primer thiolated oligonucleotide, complementary to the
      target DNA as far as one base before the mutation site, on an electrode or a gold
      quartz piezoelectric crystal. After hybridizing the target DNA, normal or mutant,
      with the sensing oligonucleotide, the resulting assembly is reacted with the
      biotinylated nucleotide, complementary to the mutation site, in the presence of
      polymerase. The labeled nucleotide is coupled only to the double-stranded
      assembly that includes the mutant site. Subsequent binding of avidin-alkaline
      phosphatase to the assembly, and the biocatalyzed precipitation of an insoluble
      product on the transducer, provides a means to confirm and amplify detection of
      the mutant. Faradaic impedance spectroscopy and microgravimetric quartz-crystal
      microbalance analyses were employed for electronic detection of single-base
      mutants. The lower limit of sensitivity for the detection of the mutant DNA is 1
      x 10-14 mol/ml. We applied the method for the analysis of polymorphic blood
      samples that include the Tay-Sachs genetic disorder. The sensitivity of the
      method enables the quantitative analysis of the mutant with no PCR pre
      amplification.

PMID- 11231560
TI  - Fingerprinting polysaccharides with single-molecule atomic force microscopy.
AB  - We report the use of an atomic force microscopy (AFM)-based force spectroscopy
      technique to identify, at the single-molecule level, the components of mixtures
      of polysaccharides. Previously, we showed that the elasticity of certain types of
      polysaccharides is governed by force-induced conformational transitions of the
      pyranose ring. These transitions produce atomic fingerprints in the force
      extension spectrum that are characteristic of the ground-energy conformation of
      the pyranose ring and the type of glycosidic linkages. Using this approach we
      find that commercially available agarose and lambda-carrageenan contain molecules
      that, when stretched in an atomic force microscope, produce a force spectrum
      characteristic of alpha-(1-->4) d-glucans. We have identified these molecules as
      amylopectin or floridean starch, a storage polysaccharide in algae. Our
      methodology can identify individual polysaccharide molecules in solution, which
      is not possible by any other spectroscopic technique, and therefore is an
      important addition to the arsenal of analytical techniques used in carbohydrate
      research.

PMID- 11231561
TI  - Constitutive expression of Arabidopsis LEAFY or APETALA1 genes in citrus reduces
      their generation time.
AB  - Citrus trees have a long juvenile phase that delays their reproductive
      development by between 6 and 20 years, depending on the species. With the aim of
      accelerating their flowering time, we transformed juvenile citrus seedlings to
      constitutively express the Arabidopsis LEAFY (LFY) or APETALA1 (AP1) genes, which
      promote flower initiation in Arabidopsis. Both types of transgenic citrus
      produced fertile flowers and fruits as early as the first year, notably through a
      mechanism involving an appreciable shortening of their juvenile phase.
      Furthermore, expression of AP1 was as efficient as LFY in the initiation of
      flowers, and did not produce any severe developmental abnormality. Both types of
      transgenic trees flowered in consecutive years, and their flowering response was
      under environmental control. In addition, zygotic and nucellar derived transgenic
      seedlings had a very short juvenile phase and flowered in their first spring,
      demonstrating the stability and inheritance of this trait. These results open new
      possibilities for domestication, genetic improvement, and experimental research
      in citrus and other woody species.

PMID- 11231562
TI  - Acceleration of potato tuber sprouting by the expression of a bacterial
      pyrophosphatase.
AB  - Potato is a globally important crop. Unfortunately, potato farming is plagued
      with problems associated with the sprouting behavior of seed tubers. The data
      presented here demonstrate that using transgenic technology can influence this
      behavior. Transgenic tubers cytosolically expressing an inorganic pyrophosphatase
      gene derived from Escherichia coli under the control of the tuber-specific
      patatin promoter display significantly accelerated sprouting. The period of
      presprouting dormancy for transgenic tubers planted immediately after harvest is
      reduced by six to seven weeks when compared to wild-type tubers. This study
      demonstrates a method with which to regulate dormancy, an important aspect of
      potato crop management.

PMID- 11231563
TI  - Up-converting phosphor reporters for nucleic acid microarrays.
AB  - An important application of robotically spotted DNA microarrays is the monitoring
      of RNA expression levels. A clear limitation of this technology is the relatively
      large amount of RNA that is required per hybridization as a result of low
      hybridization efficiency and limiting detection sensitivity provided by
      conventional fluorescent reporters. We have used a recently introduced
      luminescent reporter technology, called UPT (up-converting phosphor technology).
      Down-converting phosphors have been applied before to detect nucleic acids on
      filters using time-resolved fluorometry. The unique feature of the phosphor
      particles (size 0.4 microm) used here is that they emit visible light when
      illuminated with infrared (IR) light (980 nm) as a result of a phenomenon called
      up-conversion. Because neither support material of microarrays nor biomolecules
      possess up-conversion properties, an enhanced image contrast is expected when
      these nonfading phosphor particles are applied to detect nucleic acid hybrids on
      microarrays. Comparison of the UPT reporter to cyanin 5 (Cy5) in a low-complexity
      model system showed a two order of maginitude linear relationship between
      phosphor luminescence and target concentration and resulted in an excellent
      correlation between the two reporter systems for variable target concentrations
      (R2 = 0.95). However, UPT proved to be superior in sensitivity, even though a
      wide-field microscope equipped with a xenon lamp was used. This higher
      sensitivity was demonstrated by complementary DNA (cDNA) microarray
      hybridizations using cDNAs for housekeeping genes as probes and complex cDNA as
      target. These results suggest that a UPT reporter technology in combination with
      a dedicated IR laser array-scanner holds significant promise for various
      microarray applications.

PMID- 11231565
TI  - Patent due diligence in biotechnology transactions.

PMID- 11231566
TI  - Recent patents in proteomics.

PMID- 11231569
TI  - University bioinformatics programs on the rise.

PMID- 11231570
TI  - Ran stimulates spindle assembly by altering microtubule dynamics and the balance
      of motor activities.
AB  - The guanosine tri-phosphatase Ran stimulates assembly of microtubule spindles.
      However, it is not known what aspects of the microtubule cytoskeleton are subject
      to regulation by Ran in mitosis. Here we show that Ran-GTP stimulates microtubule
      assembly by increasing the rescue frequency of microtubules three- to eightfold.
      In addition to changing microtubule dynamics, Ran-GTP also alters the balance of
      motor activities, partly as a result of an increase in the amount of motile Eg5,
      a plus-end-directed microtubule motor that is essential for spindle formation.
      Thus, Ran regulates multiple processes that are involved in spindle assembly.

PMID- 11231571
TI  - Ran-GTP coordinates regulation of microtubule nucleation and dynamics during
      mitotic-spindle assembly.
AB  - It was recently reported that GTP-bound Ran induces microtubule and pseudo
      spindle assembly in mitotic egg extracts in the absence of chromosomes and
      centrosomes, and that chromosomes induce the assembly of spindle microtubules in
      these extracts through generation of Ran-GTP. Here we examine the effects of Ran
      GTP on microtubule nucleation and dynamics and show that Ran-GTP has independent
      effects on both the nucleation activity of centrosomes and the stability of
      centrosomal microtubules. We also show that inhibition of Ran-GTP production,
      even in the presence of duplicated centrosomes and kinetochores, prevents
      assembly of a bipolar spindle in M-phase extracts.

PMID- 11231572
TI  - Role of actin polymerization and actin cables in actin-patch movement in
      Schizosaccharomyces pombe.
AB  - Factors that are involved in actin polymerization, such as the Arp2/3 complex,
      have been found to be packaged into discrete, motile, actin-rich foci. Here we
      investigate the mechanism of actin-patch motility in S. pombe using a fusion of
      green fluorescent protein (GFP) to a coronin homologue, Crn1p. Actin patches are
      associated with cables and move with rates of 0.32 microm s(-1) primarily in an
      undirected manner at cell tips and also in a directed manner along actin cables,
      often away from cell tips. Patches move more slowly or stop when actin
      polymerization is attenuated by Latrunculin A or in arp3 and cdc3 (profilin)
      mutants. In a cdc8 (tropomyosin) mutant, actin cables are absent, and patches
      move with similar speed but in a non-directed manner. Patches are sites of Arp3
      dependent F-actin polymerization in vitro. Rapid F-actin turnover rates in vivo
      indicate that patches and cables are maintained continuously by actin
      polymerization. Our studies give rise to a model in which actin patches are
      centres for actin polymerization that drive their own movement on actin cables
      using Arp2/3-based actin polymerization.

PMID- 11231573
TI  - Cytoplasmic localization of p21Cip1/WAF1 by Akt-induced phosphorylation in HER
      2/neu-overexpressing cells.
AB  - Amplification or overexpression of HER-2/neu in cancer cells confers resistance
      to apoptosis and promotes cell growth. The cellular localization of p21Cip1/WAF1
      has been proposed to be critical either in promoting cell survival or in
      inhibiting cell growth. Here we show that HER-2/neu-mediated cell growth requires
      the activation of Akt, which associates with p21Cip1/WAF1 and phosphorylates it
      at threonine 145, resulting in cytoplasmic localization of p21Cip1/WAF1.
      Furthermore, blocking the Akt pathway with a dominant-negative Akt mutant
      restores the nuclear localization and cell-growth-inhibiting activity of
      p21Cip1/WAF1. Our results indicate that HER-2/neu induces cytoplasmic
      localization of p21Cip1/WAF1 through activation of Akt to promote cell growth,
      which may have implications for the oncogenic activity of HER-2/neu and Akt.

PMID- 11231574
TI  - Sequential-replenishment mechanism of exocytosis in pancreatic acini.
AB  - Here we report exocytosis of zymogen granules, as examined by multiphoton
      excitation imaging in intact pancreatic acini. Cholecystokinin induces Ca 2+
      oscillations that trigger exocytosis when the cytosolic Ca 2+ concentration
      exceeds 1 microM. Zymogen granules fused with the plasma membrane maintain their
      Omega-shaped profile for an average of 220 s and serve as targets for sequential
      fusion of granules that are located within deeper layers of the cell. This
      secondary exocytosis occurs as rapidly as the primary exocytosis and accounts for
      most exocytotic events. Granule-granule fusion does not seem to precede primary
      exocytosis, indicating that secondary fusion events may require a plasma-membrane
      factor. This sequential-replenishment mechanism of exocytosis allows the cell to
      take advantage of a large supply of fusion-ready granules without needing to
      transport them to the plasma membrane.

PMID- 11231575
TI  - Activation of Arp2/3 complex-mediated actin polymerization by cortactin.
AB  - Cortactin, a filamentous actin (F-actin)-associated protein and prominent
      substrate of Src, is implicated in progression of breast tumours through gene
      amplification at chromosome 11q13. However, the function of cortactin remains
      obscure. Here we show that cortactin co-localizes with the Arp2/3 complex, a de
      novo actin nucleator, at dynamic particulate structures enriched with actin
      filaments. Cortactin binds directly to the Arp2/3 complex and activates it to
      promote nucleation of actin filaments. The interaction of cortactin with the
      Arp2/3 complex occurs at an amino-terminal domain that is rich in acidic amino
      acids. Mutations in a conserved amino-acid sequence of DDW abolish both the
      interaction with the Arp2/3 complex and complex activation. The N-terminal domain
      is not only essential but also sufficient to target cortactin to actin-enriched
      patches within cells. Interestingly, the ability of cortactin to activate the
      Arp2/3 complex depends on an activity for F-actin binding, which is almost 20
      fold higher than that of the Arp2/3 complex. Our data indicate a new mechanism
      for activation of actin polymerization involving an enhanced interaction between
      the Arp2/3 complex and actin filaments.

PMID- 11231577
TI  - Bag1-Hsp70 mediates a physiological stress signalling pathway that regulates Raf
      1/ERK and cell growth.
AB  - Survival after stress requires the precise orchestration of cell-signalling
      events to ensure that biosynthetic processes are alerted and cell survival
      pathways are initiated. Here we show that Bag1, a co-chaperone for heat-shock
      protein 70 (Hsp70), coordinates signals for cell growth in response to cell
      stress, by downregulating the activity of Raf-1 kinase. Raf-1 and Hsp70 compete
      for binding to Bag1, such that Bag1 binds to and activates Raf-1, subsequently
      activating the downstream extracellular signal-related kinases (ERKs). When
      levels of Hsp70 are elevated after heat shock, or in cells conditionally
      overexpressing Hsp70, Bag1-Raf-1 is displaced by Bag1-Hsp70, and DNA synthesis is
      arrested. Mutants Bag1C204A and Bag1E208A, which cannot bind Hsp70,
      constitutively activate Raf-1/ERK kinases but are unaffected by Hsp70;
      consequently neither Bag1-Raf-1 nor DNA synthesis is negatively affected during
      heat shock. Likewise, mutants Hsp70F245S, Hsp70R262W and Hsp70L282R, which retain
      chaperone activity but do not bind to Bag1, fail to repress Bag1 activation of
      Raf-1/ERK kinase. We propose that Bag1 functions in the heat-shock response to
      coordinate cell growth signals and mitogenesis, and that Hsp70 functions as a
      sensor in stress signalling.

PMID- 11231576
TI  - A plasma kallikrein-dependent plasminogen cascade required for adipocyte
      differentiation.
AB  - Here we show that plasma kallikrein (PKal) mediates a plasminogen (Plg) cascade
      in adipocyte differentiation. Ecotin, an inhibitor of serine proteases, inhibits
      cell-shape change, adipocyte-specific gene expression, and lipid accumulation
      during adipogenesis in culture. Deficiency of Plg, but not of urokinase or tissue
      type plasminogen activator, suppresses adipogenesis during differentiation of 3T3
      L1 cells and mammary-gland involution. PKal, which is inhibited by ecotin, is
      required for adipose conversion, Plg activation and 3T3-L1 differentiation. Human
      plasma lacking PKal does not support differentiation of 3T3-L1 cells. PKal is
      therefore a physiological regulator that acts in the Plg cascade during
      adipogenesis. We propose that the Plg cascade fosters adipocyte differentiation
      by degradation of the fibronectin-rich preadipocyte stromal matrix.

PMID- 11231578
TI  - c-myc overexpression activates alternative pathways for intracellular proteolysis
      in lymphoma cells.
AB  - Burkitt's lymphoma (BL) is a highly malignant B-cell tumour characterized by
      chromosomal translocations that constitutively activate the c-myc oncogene. Here
      we show that BL cells are resistant to apoptosis and do not accumulate ubiquitin
      conjugates in response to otherwise toxic doses of inhibitors of the proteasome.
      Deubiquitinating enzymes and the cytosolic subtilisin-like protease
      tripeptidylpeptidase II are upregulated in BLs, and could be rapidly induced by
      the overexpression of c-myc in normal B cells carrying oestrogen-driven
      recombinant Epstein-Barr virus. Apoptosis was induced by inhibiting
      tripeptidylpeptidase II, suggesting that the activity of this protease may be
      required for the survival of BL cells. We thus show that there is a regulatory
      link between c-myc activation and changes in proteolysis that may affect
      malignant transformation.

PMID- 11231579
TI  - DNA replication control through interaction of E2F-RB and the origin recognition
      complex.
AB  - The E2F transcription factor and retinoblastoma protein control cell-cycle
      progression and DNA replication during S phase. Mutations in the Drosophila dE2F1
      and dDP genes affect the origin recognition complex (DmORC) and initiation of
      replication at the chorion gene replication origin. Here we show that mutants of
      Rbf (an retinoblastoma protein homologue) fail to limit DNA replication. We also
      show that the dDP, dE2F1 and Rbf proteins are located in a complex with DmORC,
      and that dE2F1 and DmORC are bound to the chorion origin of replication in vivo.
      Our results indicate that dE2F1 and Rbf function together at replication origins
      to limit DNA replication through interactions with DmORC.

PMID- 11231580
TI  - Distinct roles for Galpha and Gbetagamma in regulating spindle position and
      orientation in Caenorhabditis elegans embryos.
AB  - Correct placement and orientation of the mitotic spindle is essential for
      segregation of localized components and positioning of daughter cells. Although
      these processes are important in many cells, few factors that regulate spindle
      placement are known. Previous work has shown that GPB-1, the Gbeta subunit of a
      heterotrimeric G protein, is required for orientation of early cell division axes
      in C. elegans embryos. Here we show that GOA-1 (a Galphao) and the related GPA-16
      are the functionally redundant Galpha subunits and that GPC-2 is the relevant
      Ggamma subunit that is required for spindle orientation in the early embryo. We
      show that Galpha and Gbetagamma are involved in controlling distinct microtubule
      dependent processes. Gbetagamma is important in regulating migration of the
      centrosome around the nucleus and hence in orientating the mitotic spindle.
      Galpha is required for asymmetric spindle positioning in the one-celled embryo.

PMID- 11231581
TI  - Influenza virus propagation is impaired by inhibition of the Raf/MEK/ERK
      signalling cascade.
AB  - Influenza A viruses are important worldwide pathogens in humans and different
      animal species. The functions of most of the ten different viral proteins of this
      negative-strand RNA virus have been well elucidated. However, little is known
      about the virus-induced intracellular signalling events that support viral
      replication. The Raf/MEK/ERK cascade is the prototype of mitogen-activated
      protein (MAP) kinase cascades and has an important role in cell growth,
      differentiation and survival. Investigation of the function of this pathway has
      been facilitated by the identification of specific inhibitors such as U0126,
      which blocks the cascade at the level of MAPK/ERK kinase (MEK). Here we show that
      infection of cells with influenza A virus leads to biphasic activation of the
      Raf/MEK/ERK cascade. Inhibition of Raf signalling results in nuclear retention of
      viral ribonucleoprotein complexes (RNPs), impaired function of the nuclear-export
      protein (NEP/NS2) and concomitant inhibition of virus production. Thus,
      signalling through the mitogenic cascade seems to be essential for virus
      production and RNP export from the nucleus during the viral life cycle.

PMID- 11231582
TI  - The Arp2/3 complex nucleates actin filament branches from the sides of pre
      existing filaments.
AB  - Regulated assembly of actin-filament networks provides the mechanical force that
      pushes forward the leading edge of motile eukaryotic cells and intracellular
      pathogenic bacteria and viruses. When activated by binding to actin filaments and
      to the WA domain of Wiskott-Aldrich-syndrome protein (WASP)/Scar proteins, the
      Arp2/3 complex nucleates new filaments that grow from their barbed ends. The
      Arp2/3 complex binds to the sides and pointed ends of actin filaments, localizes
      to distinctive 70 degrees actin-filament branches present in lamellae, and forms
      similar branches in vitro. These observations have given rise to the dendritic
      nucleation model for actin-network assembly, in which the Arp2/3 complex
      initiates branches on the sides of older filaments. Recently, however, an
      alternative mechanism for branch formation has been proposed. In the 'barbed-end
      nucleation' model, the Arp2/3 complex binds to the free barbed end of a filament
      and two filaments subsequently grow from the branch. Here we report the use of
      kinetic and microscopic experiments to distinguish between these models. Our
      results indicate that the activated Arp2/3 complex preferentially nucleates
      filament branches directly on the sides of pre-existing filaments.

PMID- 11231583
TI  - A myosin II mutation uncouples ATPase activity from motility and shortens step
      size.
AB  - It is thought that Switch II of myosin, kinesin and G proteins has an important
      function in relating nucleotide state to protein conformation. Here we examine a
      myosin mutant containing an S456L substitution in the Switch II region. In this
      protein, mechanical activity is uncoupled from the chemical energy of ATP
      hydrolysis so that its gliding velocity on actin filaments is only one-tenth of
      that of the wild type. The mutant spends longer in the strongly bound state and
      exhibits a shorter step size, which together account for the reduction in in
      vitro velocity. This is the first single point mutation in myosin that has been
      found to affect step size.

PMID- 11231584
TI  - Rac recruits high-affinity integrin alphavbeta3 to lamellipodia in endothelial
      cell migration.
AB  - Integrin alphavbeta3 has an important role in the proliferation, survival,
      invasion and migration of vascular endothelial cells. Like other integrins,
      alphavbeta3 can exist in different functional states with respect to ligand
      binding. These changes involve both affinity modulation, by which conformational
      changes in the integrin heterodimer govern affinity for individual extracellular
      matrix proteins, and avidity modulation, by which changes in lateral mobility and
      integrin clustering affect the binding of cells to multivalent matrices. Here we
      have used an engineered monoclonal antibody Fab (antigen-binding fragment) named
      WOW-1, which binds to activated integrins alphavbeta3 and alphavbeta5 from
      several species, to investigate the role of alphavbeta3 activation in endothelial
      cell behaviour. Because WOW-1 is monovalent, it is insensitive to changes in
      integrin clustering and therefore reports only changes in affinity. WOW-1
      contains an RGD tract in its variable region and binds only to unoccupied, high
      affinity integrins. By using WOW-1, we have identified the selective recruitment
      of high-affinity integrins as a mechanism by which lamellipodia promote formation
      of new adhesions at the leading edge in cell migration.

PMID- 11231585
TI  - The cell-cycle regulatory protein Cks1 is required for SCF(Skp2)-mediated
      ubiquitinylation of p27.
AB  - The cyclin-dependent kinase (CDK) inhibitor p27 is degraded in late G1 phase by
      the ubiquitin pathway, allowing CDK activity to drive cells into S phase.
      Ubiquitinylation of p27 requires its phosphorylation at Thr 187 (refs 3, 4) and
      subsequent recognition by S-phase kinase associated protein 2 (Skp2; refs 5-8), a
      member of the F-box family of proteins that associates with Skp1, Cul-1 and
      ROC1/Rbx1 to form an SCF ubiquitin ligase complex. However, in vitro ligation of
      p27 to ubiquitin could not be reconstituted by known purified components of the
      SCFSkp2 complex. Here we show that the missing factor is CDK subunit 1 (Cks1),
      which belongs to the highly conserved Suc1/Cks family of proteins that bind to
      some CDKs and phosphorylated proteins and are essential for cell-cycle
      progression. Human Cks1, but not other members of the family, reconstitutes
      ubiquitin ligation of p27 in a completely purified system, binds to Skp2 and
      greatly increases binding of T187-phosphorylated p27 to Skp2. Our results
      represent the first evidence that an SCF complex requires an accessory protein
      for activity as well as for binding to its phosphorylated substrate.

PMID- 11231587
TI  - Big genome--big science?

PMID- 11231586
TI  - ERK phosphorylation drives cytoplasmic accumulation of hnRNP-K and inhibition of
      mRNA translation.
AB  - Heterogeneous nuclear ribonucleoprotein K (hnRNP-K) is one of a family of 20
      proteins that are involved in transcription and post-transcriptional messenger
      RNA metabolism. The mechanisms that underlie regulation of hnRNP-K activities
      remain largely unknown. Here we show that cytoplasmic accumulation of hnRNP-K is
      phosphorylation-dependent. Mitogen-activated protein kinase/extracellular-signal
      regulated kinase (MAPK/ERK) efficiently phosphorylates hnRNP-K both in vitro and
      in vivo at serines 284 and 353. Serum stimulation or constitutive activation of
      ERK kinase (MEK1) results in phosphorylation and cytoplasmic accumulation of
      hnRNP-K. Mutation at ERK phosphoacceptor sites in hnRNP-K abolishes the ability
      to accumulate in the cytoplasm and renders the protein incapable of regulating
      translation of mRNAs that have a differentiation-control element (DICE) in the 3'
      untranslated region (UTR). Similarly, treatment with a pharmacological inhibitor
      of the ERK pathway abolishes cytoplasmic accumulation of hnRNP-K and attenuates
      inhibition of mRNA translation. Our results establish the role of MAPK/ERK in
      phosphorylation-dependent cellular localization of hnRNP-K, which is required for
      its ability to silence mRNA translation.

PMID- 11231588
TI  - Spindles cotton on to junctions, APC and EB1.

PMID- 11231589
TI  - Ran hits the ground running.

PMID- 11231590
TI  - Akt takes centre stage in cell-cycle deregulation.

PMID- 11231591
TI  - New tricks for an old dog?

PMID- 11231596
TI  - Will the US clone alone?

PMID- 11231595
TI  - The cell biology of neuronal navigation.
AB  - Morphogenesis of the nervous system requires the directed migration of
      postmitotic neurons to designated locations in the nervous system and the
      guidance of axon growth cones to their synaptic targets. Evidence suggests that
      both forms of navigation depend on common guidance molecules, surface receptors
      and signal transduction pathways that link receptor activation to cytoskeletal
      reorganization. Future challenges remain not only in identifying all the
      components of the signalling pathways, but also in understanding how these
      pathways achieve signal amplification and adaptation-two essential cellular
      processes for neuronal navigation.

PMID- 11231597
TI  - Perinatal omega-3 fatty acid deficiency affects blood pressure later in life.

PMID- 11231598
TI  - Countering the 'counterattack' hypothesis.

PMID- 11231599
TI  - Scientists race to develop a blood test for vCJD.

PMID- 11231601
TI  - Experts predict bleak post-genomic era for drug R&D.

PMID- 11231603
TI  - Bush is a threat to US stem-cell research.

PMID- 11231610
TI  - Sir John Sulston.

PMID- 11231611
TI  - The early days of DNA sequences.
AB  - Fred Sanger was awarded the rare distinction of two Nobel Prizes for Chemistry,
      in 1958 and 1980. The first was for his work on the structure of proteins,
      particularly that of insulin, the latter for his contribution concerning the
      determination of nucleic acid sequences, the foundation work that ultimately led
      to The Human Genome Project.

PMID- 11231612
TI  - Legal issues in genomic medicine.
AB  - Society has entered uncharted territory regarding how, when and where genetic
      information can be used. This article discusses the major issues raised by
      increased access to genomic information, which will ultimately be resolved by
      legislation or the courts.

PMID- 11231613
TI  - Immune privilege or inflammation? Insights into the Fas ligand enigma.
AB  - Fas ligand (FasL) has become an enigmatic molecule: some evidence indicates that
      it contributes to immune privilege in tissues and tumors, whereas other data
      demonstrates that FasL can elicit inflammation. New findings may begin to
      reconcile the paradoxical effects of FasL.

PMID- 11231616
TI  - Putting the genes for type II diabetes on the map.

PMID- 11231618
TI  - Pharmacogenetic applications of the Human Genome project.

PMID- 11231617
TI  - Zeroing in on tolerance.

PMID- 11231619
TI  - Gazing into a crystal ball-cancer therapy in the post-genomic era.

PMID- 11231620
TI  - CYP3A genetics in drug metabolism.

PMID- 11231621
TI  - The heart of genomics.

PMID- 11231622
TI  - Blood simple prion diagnostics.

PMID- 11231623
TI  - A role for fibronectin in self-repair after ischemic injury.

PMID- 11231624
TI  - The neglected ion: HCO3-.

PMID- 11231625
TI  - Eyeing a new route along an old pathway.

PMID- 11231626
TI  - Antigen persistence in HIV resistance.

PMID- 11231627
TI  - Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL
      cross-priming.
AB  - The initiation of T-cell-mediated antitumor immune responses requires the uptake
      and processing of tumor antigens by dendritic cells and their presentation on MHC
      I molecules. Here we show in a human in vitro model system that exosomes, a
      population of small membrane vesicles secreted by living tumor cells, contain and
      transfer tumor antigens to dendritic cells. After mouse tumor exosome uptake,
      dendritic cells induce potent CD8+ T-cell-dependent antitumor effects on
      syngeneic and allogeneic established mouse tumors. Therefore, exosomes represent
      a novel source of tumor-rejection antigens for T-cell cross priming, relevant for
      immunointerventions.

PMID- 11231629
TI  - In vivo gene therapy of metachromatic leukodystrophy by lentiviral vectors:
      correction of neuropathology and protection against learning impairments in
      affected mice.
AB  - Metachromatic leukodystrophy (MLD) is a lipidosis caused by deficiency of
      arylsulfatase A (ARSA). Although the genetics of MLD are known, its
      pathophysiology is not understood. The disease leads to progressive demyelination
      and early death and no effective treatment is available. We used lentiviral
      vectors to deliver a functional ARSA gene (human ARSA) into the brain of adult
      mice with germ-line inactivation of the mouse gene encoding ARSA, As2. We report
      sustained expression of active enzyme throughout a large portion of the brain,
      with long-term protection from development of neuropathology and hippocampal
      related learning impairments. We show that selective degeneration of hippocampal
      neurons is a central step in disease pathogenesis, and provide evidence that in
      vivo transfer of ARSA by lentiviral vectors reverts the disease phenotype in all
      investigated areas. Therefore, in vivo gene therapy offers a unique option for
      MLD and other storage diseases affecting the central nervous system.

PMID- 11231628
TI  - Activation of a tissue-specific stress response in the aqueous outflow pathway of
      the eye defines the glaucoma disease phenotype.
AB  - The glaucomas are a group of optic neuropathies comprising the leading cause of
      irreversible blindness worldwide. Elevated intraocular pressure due to a
      reduction in normal aqueous outflow is a major causal risk factor. We found that
      endothelial leukocyte adhesion molecule-1 (ELAM-1), the earliest marker for the
      atherosclerotic plaque in the vasculature, was consistently present on trabecular
      meshwork (TM) cells in the outflow pathways of eyes with glaucomas of diverse
      etiology. We determined expression of ELAM-1 to be controlled by activation of an
      interleukin-1 (IL-1) autocrine feedback loop through transcription factor NF
      kappaB, and activity of this signaling pathway was shown to protect TM cells
      against oxidative stress. These findings characterize a protective stress
      response specific to the eye's aqueous outflow pathways and provide the first
      known diagnostic indicator of glaucomatous TM cells. They further indicate that
      common mechanisms contribute to the pathophysiology of the glaucomas and vascular
      diseases.

PMID- 11231630
TI  - ORP150 protects against hypoxia/ischemia-induced neuronal death.
AB  - Oxygen-regulated protein 150 kD (ORP150) is a novel endoplasmic-reticulum
      associated chaperone induced by hypoxia/ischemia. Although ORP150 was sparingly
      upregulated in neurons from human brain undergoing ischemic stress, there was
      robust induction in astrocytes. Cultured neurons overexpressing ORP150 were
      resistant to hypoxemic stress, whereas astrocytes with inhibited ORP150
      expression were more vulnerable. Mice with targeted neuronal overexpression of
      ORP150 had smaller strokes compared with controls. Neurons with increased ORP150
      demonstrated suppressed caspase-3-like activity and enhanced brain-derived
      neurotrophic factor (BDNF) under hypoxia signaling. These data indicate that
      ORP150 is an integral participant in ischemic cytoprotective pathways.

PMID- 11231631
TI  - Plasma fibronectin supports neuronal survival and reduces brain injury following
      transient focal cerebral ischemia but is not essential for skin-wound healing and
      hemostasis.
AB  - Fibronectin performs essential roles in embryonic development and is prominently
      expressed during tissue repair. Two forms of fibronectin have been identified:
      plasma fibronectin (pFn), which is expressed by hepatocytes and secreted in
      soluble form into plasma; and cellular fibronectin (cFn), an insoluble form
      expressed locally by fibroblasts and other cell types and deposited and assembled
      into the extracellular matrix. To investigate the role of pFn in vivo, we
      generated pFn-deficient adult mice using Cre-loxP conditional gene-knockout
      technology. Here we show that pFn-deficient mice show increased neuronal
      apoptosis and larger infarction areas following transient focal cerebral
      ischemia. However, pFn is dispensable for skin-wound healing and hemostasis.

PMID- 11231632
TI  - Persistently modified h-channels after complex febrile seizures convert the
      seizure-induced enhancement of inhibition to hyperexcitability.
AB  - Febrile seizures are the most common type of developmental seizures, affecting up
      to 5% of children. Experimental complex febrile seizures involving the immature
      rat hippocampus led to a persistent lowering of seizure threshold despite an
      upregulation of inhibition. Here we provide a mechanistic resolution to this
      paradox by showing that, in the hippocampus of rats that had febrile seizures,
      the long-lasting enhancement of the widely expressed intrinsic membrane
      conductance Ih converts the potentiated synaptic inhibition to hyperexcitability
      in a frequency-dependent manner. The altered gain of this molecular inhibition
      excitation converter reveals a new mechanism for controlling the balance of
      excitation-inhibition in the limbic system. In addition, here we show for the
      first time that h-channels are modified in a human neurological disease paradigm.

PMID- 11231633
TI  - Clusterin contributes to caspase-3-independent brain injury following neonatal
      hypoxia-ischemia.
AB  - Clusterin, also known as apolipoprotein J, is a ubiquitously expressed molecule
      thought to influence a variety of processes including cell death. In the brain,
      it accumulates in dying neurons following seizures and hypoxic-ischemic (H-I)
      injury. Despite this, in vivo evidence that clusterin directly influences cell
      death is lacking. Following neonatal H-I brain injury in mice (a model of
      cerebral palsy), there was evidence of apoptotic changes (neuronal caspase-3
      activation), as well as accumulation of clusterin in dying neurons. Clusterin
      deficient mice had 50% less brain injury following neonatal H-I. Surprisingly,
      the absence of clusterin had no effect on caspase-3 activation, and clusterin
      accumulation and caspase-3 activation did not colocalize to the same cells.
      Studies with cultured cortical neurons demonstrated that exogenous purified
      astrocyte-secreted clusterin exacerbated oxygen/glucose-deprivation-induced
      necrotic death. These results indicate that clusterin may be a new therapeutic
      target to modulate non-caspase-dependent neuronal death following acute brain
      injury.

PMID- 11231634
TI  - MHC-I-restricted presentation of HIV-1 virion antigens without viral replication.
AB  - Dendritic cells and macrophages can process extracellular antigens for
      presentation by MHC-I molecules. This exogenous pathway may have a crucial role
      in the activation of CD8+ cytotoxic T lymphocytes during human viral infections.
      We show here that HIV-1 epitopes derived from incoming virions are presented
      through the exogenous MHC-I pathway in primary human dendritic cells, and to a
      lower extent in macrophages, leading to cytotoxic T-lymphocyte activation in the
      absence of viral protein synthesis. Exogenous antigen presentation required
      adequate virus-receptor interactions and fusion of viral and cellular membranes.
      These results provide new insights into how anti-HIV cytotoxic T lymphocytes can
      be activated and have implications for anti-HIV vaccine design.

PMID- 11231635
TI  - Epstein-Barr virus nuclear protein EBNA-3C interacts with the human metastatic
      suppressor Nm23-H1: a molecular link to cancer metastasis.
AB  - Epstein-Barr virus (EBV) is an oncogenic virus associated with a number of human
      malignancies including Burkitt lymphoma, nasopharyngeal carcinoma,
      lymphoproliferative disease and, though still debated, breast carcinoma. A subset
      of latent EBV antigens is required for mediating immortalization of primary B
      lymphocytes. Here we demonstrate that the carboxy-terminal region of the
      essential latent antigen, EBNA-3C, interacts specifically with the human
      metastatic suppressor protein Nm23-H1. Moreover, EBNA-3C reverses the ability of
      Nm23-H1 to suppress the migration of Burkitt lymphoma cells and breast carcinoma
      cells. We propose that EBNA-3C contributes to EBV-associated human cancers by
      targeting and altering the role of the metastasis suppressor Nm23-H1.

PMID- 11231636
TI  - Changing the dosing schedule minimizes the disruptive effects of interferon on
      clock function.
AB  - The effectiveness and toxicity of many drugs vary depending on the relationship
      between the dosing schedule and the 24-hour rhythms of biochemical, physiological
      and behavioral processes. In addition, several drugs can cause alterations to the
      24-hour rhythms leading to illness and altered homeostatic regulation. However,
      the mechanisms of this drug-based disruption of circadian 'clock' genes remain
      unclear. Here, we show the disruptive effect of interferon-alpha on the rhythm of
      locomotor activity, body temperature and clock-gene mRNA expression in the
      periphery and suprachiasmatic nuclei, a primary circadian pacemaker. The
      rhythmicity of clock genes and the photic induction of the Per gene in
      suprachiasmatic nuclei were disturbed by the repetitive administration of
      interferon-alpha. Moreover, alteration of clock function, a new concept of
      adverse effects, can be overcome by optimizing the dosing schedule to minimize
      adverse drug effects.

PMID- 11231637
TI  - A novel erythroid-specific marker of transmissible spongiform encephalopathies.
AB  - Transmissible spongiform encephalopathies (TSE) are a group of invariably fatal
      neurodegenerative diseases and include scrapie in sheep, bovine spongiform
      encephalopathy (BSE) in cattle, chronic wasting disease in deer and elk, and Kuru
      disease, Creutzfeldt-Jakob disease (CJD) and variant CJD in humans. The
      pathological effects of disease occur predominantly in the CNS (central nervous
      system), where common hallmarks include vacuolation, gliosis, accumulation of a
      protease-resistant, abnormally folded isoform of the prion protein (PrPSc) and
      neuronal cell death. Lack of understanding of the molecular mechanisms underlying
      disease pathogenesis, particularly in non-CNS tissues, means that there are
      currently no effective strategies for early diagnosis or therapeutic intervention
      of TSEs. Here we report the first identification of a molecular marker that is
      easily detectable in readily accessible tissues. We demonstrate that a dramatic
      decrease in expression of a transcript specific to erythroid lineage cells is a
      common feature of TSEs. Our findings indicate a previously unrecognized role for
      involvement of the erythroid lineage in the etiology of TSE pathogenesis and
      should provide a new focus for research into diagnostic and therapeutic
      strategies.

PMID- 11231638
TI  - Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia
      gravis without acetylcholine receptor antibodies.
AB  - Myasthenia gravis (MG) is an antibody-mediated autoimmune disease of the
      neuromuscular junction. In approximately 80% of patients, auto-antibodies to the
      muscle nicotinic acetylcholine receptor (AChR) are present. These antibodies
      cause loss of AChR numbers and function, and lead to failure of neuromuscular
      transmission with muscle weakness. The pathogenic mechanisms acting in the 20% of
      patients with generalized MG who are seronegative for AChR-antibodies (AChR-Ab)
      have not been elucidated, but there is evidence that they also have an antibody
      mediated disorder, with the antibodies directed towards another, previously
      unidentified muscle-surface-membrane target. Here we show that 70% of AChR-Ab
      seronegative MG patients, but not AChR-Ab-seropositive MG patients, have serum
      auto-antibodies against the muscle-specific receptor tyrosine kinase, MuSK. MuSK
      mediates the agrin-induced clustering of AChRs during synapse formation, and is
      also expressed at the mature neuromuscular junction. The MuSK antibodies were
      specific for the extracellular domains of MuSK expressed in transfected COS7
      cells and strongly inhibited MuSK function in cultured myotubes. Our results
      indicate the involvement of MuSK antibodies in the pathogenesis of AChR-Ab
      seronegative MG, thus defining two immunologically distinct forms of the disease.
      Measurement of MuSK antibodies will substantially aid diagnosis and clinical
      management.

PMID- 11231639
TI  - Imaging of amyloid-beta deposits in brains of living mice permits direct
      observation of clearance of plaques with immunotherapy.

PMID- 11231640
TI  - Cell identification and isolation on the basis of cytokine secretion: a novel
      tool for investigating immune responses.

PMID- 11231641
TI  - A novel non-invasive, in vivo technique for the quantification of leukocyte
      rolling and extravasation at sites of inflammation in human patients.

PMID- 11231643
TI  - Interview with Bernhard Meier, MD. Interview by Laurie Gustafson.

PMID- 11231644
TI  - Phosphorylcholine-coated stents in porcine coronary arteries: in vivo assessment
      of biocompatibility.
AB  - AIMS: To examine the angiographic (quantitative coronary angiography),
      morphometric, light microscopic (LM) (i.e., histology and immunohistochemical
      staining) and electron microscopic (EM) findings after implantation of
      phosphorylcholine (PC)-coated compared to uncoated stents in porcine coronary
      arteries. METHODS: Forty (25 PC-coated, 15 uncoated) divYsio stents were
      implanted into the coronary arteries of 20 pigs. Quantitative coronary
      angiography (QCA) was performed pre-stent and post-implantation in fifteen pigs,
      at 28 days. Two pigs were killed at 5 days (LM and scanning EM), one pig at 14
      days (scanning EM) and 17 pigs at 28 days (LM, scanning EM, transmission EM). At
      28 days, thirty-two of 34 stented segments excised were formalin-fixed, of which
      30 were embedded in resin and sectioned for morphometry and LM. Remaining stents
      were examined by TEM and SEM. RESULTS: No angiographically occlusive thrombosis
      occurred in any of the stents. LM at 5 days showed endothelialization of PC
      coated and uncoated stents, which was also confirmed by scanning EM at 14 days.
      At 28 days, QCA and morphometry showed no significant differences between PC
      coated and uncoated stents. A few inflammatory cells were seen in both stent
      types at 5 days but there was no inflammatory or additional tissue reaction to PC
      coated compared to uncoated stents at 28 days. CONCLUSIONS: The divYsio stents,
      with or without PC coating, performed equally well in terms of acute patency, 28
      day QCA and morphometry. The PC coating allows a stent to endothelialize normally
      and is not associated with specific histological changes. The PC coating on the
      divYsio stent appears biocompatible.

PMID- 11231645
TI  - Early coronary angioplasty for acute myocardial infarction: predictors of poor
      outcome in a non-selected population.
AB  - AIMS: The objective of this study was to report the experience in the treatment
      of acute myocardial infarction (AMI) with early coronary angioplasty (PTCA) in a
      single European center during one decade, attempting to identify the
      characteristics associated with a poor prognosis in these patients. METHODS AND
      RESULTS: Eight hundred patients with AMI were treated with PTCA < 12 hours after
      symptom onset. Mean age was 64 +/- 13 years, 12% were in cardiogenic shock, AMI
      location was anterior in 61% and PTCA was performed after failed thrombolysis in
      5%. Coronary stents and abciximab were used in 51% and 10%, respectively. An
      angiographic successful result was obtained in 93%, and final TIMI flow grade 3
      was achieved in 83%. The overall in-hospital mortality rate was 12.5% (2.7%,
      16.1%, 25.7% and 63.8% in patients in Killip class I, II, III and IV,
      respectively). Over the years, an improvement in the angiographic results and a
      reduction in the rates of reinfarction and target vessel revascularization were
      observed. The independent predictors of death were age > 70 years, absence of
      hyper-cholesterolemia, anterior location, cardiogenic shock, multi-vessel disease
      and unsuccessful PTCA. The leading causes of mortality were cardiogenic shock
      (63%) and ventricular free wall rupture (14%). The rates of non-fatal
      reinfarction, documented reocclusion and in-hospital repeated revascularization
      were 2%, 3% and 4%, respectively. CONCLUSION: In most cases, PTCA performed in a
      non-selected patient population with AMI results in angiographic success.
      Mortality especially occurs in patients who are in cardiogenic shock at the
      beginning of the procedure. We have observed an improvement in the results
      throughout the course of the decade.

PMID- 11231646
TI  - Chest pain early after percutaneous coronary intervention: incidence and relation
      to ECG changes, cardiac enzymes and follow-up events.
AB  - To investigate the incidence of chest pain early after percutaneous coronary
      interventions and its correlation with ECG changes, cardiac enzymes, clinical and
      procedural variables and follow-up events, we prospectively studied 199 patients
      (84% male; mean age, 60.1 +/- 9.4 years) after primary successful percutaneous
      coronary interventions (21% PTCA; 79% additional stent implantation). During the
      first 16 hours following the intervention, the occurrence of chest pain was
      noted, ECGs were recorded and serial measurements of cardiac enzymes were
      performed. Seventy-six patients (38%) with elevated enzyme levels at time 0 were
      excluded. A clinical follow-up was obtained at 6 months. Forty patients (32.5%)
      experienced chest pain; new ECG changes were detected in 3 (2.5%). The mean
      levels of all enzymes were significantly higher in patients with chest pain 16
      hours after the intervention. In patients with chest pain versus those without,
      CK-MB mass and troponin I levels higher than twice the upper normal limit were
      seen in 43.6% versus 11.0% (p < 0.0001) and 45.0% versus 17.3% (p < 0.002),
      respectively. Elevated troponin I (< 0.004) and CK-MB mass (< 0.04) as well as
      presumed ischemic chest pain (< 0.03) could be identified as risk factors for
      recurrent chest pain during follow-up. In conclusion, chest pain was common early
      after percutaneous coronary interventions and correlated with elevated cardiac
      enzymes, suggesting peri-interventional myocardial necrosis. Elevated levels of
      CK-MB mass and troponin I, as well as presumed ischemic chest pain, were
      associated with recurrent chest pain during follow-up.

PMID- 11231647
TI  - Initial experience with a newer generation coronary stent.
AB  - BACKGROUND: Recently, several newer generation stents have become available
      promising to improve upon the results of coronary angioplasty (PTCA) with its
      attendant acute and chronic complications. The aim of this study was to
      prospectively review the results of a preliminary experience with the newer
      generation R stent in a series of 56 patients. METHODS: This study included 47
      men and 9 women, aged 57 +/- 10 years, who presented with stable angina and/or
      positive exercise testing (n = 12), unstable angina (n = 42), or acute myocardial
      infarction (n = 2). A consistent approach by a single operator for implantation
      of the R stent (Orbus Inc., The Netherlands) included stent oversizing (by 0.5
      mm) and high pressure (> 12--16 bar) deployment. Dilated vessels comprised the
      left anterior descending (n = 37) including the diagonal branch in 2 patients,
      the right coronary artery (n = 17), the left circumflex (n = 13), or a saphenous
      vein graft (n = 1). The mean left ventricular ejection fraction was 52 +/- 8% and
      the initial coronary artery stenosis was 85 +/- 8%. Stents were implanted for
      dissection and/or suboptimal PTCA result or electively. RESULTS: The procedure
      was successful in all 56 patients (100%). The residual stenosis was < 0--10%.
      Direct stenting without balloon predilation was performed in 21 patients. Single
      stents were used in 36 patients and > or = 2 stents in 20 patients. Abciximab (n
      = 22), eptifibatide (n = 8) or tirofiban (n = 1) was administered in 31 patients
      (55%). A stent-related complication was noted in one patient (stent
      misplacement). All patients were discharged alive without infarct or need for
      surgery. There were no events of subacute stent thrombosis; all patients received
      combined therapy with aspirin and clopidogrel, the latter for 1 month. In one
      patient who had received abciximab, severe thrombocytopenia (0 platelet count)
      was detected at 3 days after discharge but it was fully reversible with no
      sequelae. Over 5.2 +/- 2.8 (range, 1--11) months, there was one sudden death and
      two clinical restenoses; no other late complication occurred. CONCLUSION: Initial
      experience with 73 R stents in 56 patients and a consistent approach by a single
      operator of stent oversizing and high-pressure deployment resulted in high
      procedural success (100%), lack of stent thrombosis (0%), and a low stent-related
      complication rate (1.8%), while the design and profile of the R stent allowed for
      direct stenting in 37.5% of patients. One should be vigilant for the sporadic
      occurrence of severe thrombocytopenia with use of IIb/IIIa inhibitors.

PMID- 11231648
TI  - Use of Amplatzer septal occluder in a case of residual atrial septal defect
      causing bidirectional shunting after percutaneous Inoue mitral balloon
      valvuloplasty.
AB  - We describe a 70-year-old woman who underwent successful percutaneous Inoue
      antegrade-technique mitral valvuloplasty. Three months later, the patient
      developed right-sided heart failure. Color Doppler echocardiography and cardiac
      catheterization demonstrated an atrial septal defect with bidirectional shunting
      and no restenosis of the mitral valve (iatrogenic Lutembacher's syndrome).
      Percutaneous treatment was successfully accomplished using a 13 mm Amplatzer
      Septal Occluder (AGA Medical Corporation, Golden Valley, Minnesota). The causes
      of right-to-left shunting and the effects of body position on gas exchange in
      such patients are also discussed.

PMID- 11231649
TI  - Single coronary artery with probable origin of the anomalous right coronary
      artery from a left atrial recurrent branch.
AB  - A 62-year-old woman presented for evaluation of chest pain. She ruled out for
      myocardial infarction, and subsequent non-invasive studies were diagnostic for
      ischemia. On coronary angiography, she was found to have a previously undescribed
      variant of single coronary artery, in which the anomalous right coronary artery
      probably arose from a left atrial recurrent branch. In this patient, the
      congenital anomaly was an incidental finding, since her clinical presentation was
      felt to be due to moderate obstructive disease of the left anterior descending
      artery, in the setting of poorly controlled systemic hypertension.

PMID- 11231650
TI  - The strategic retreat and group governance.

PMID- 11231651
TI  - The hidden value of strategy-- why great practices achieve extraordinary results.

PMID- 11231652
TI  - Stent placement in iliac artery intervention: predictable and simple. Evidence
      based--not!

PMID- 11231653
TI  - Chronic total occlusion: how do we get there from here?

PMID- 11231654
TI  - Percutaneous coronary interventions in chronic total occlusions.

PMID- 11231656
TI  - Red-hot intravascular brachytherapy: is it safe for routine use?

PMID- 11231657
TI  - Toward establishing a lesion classification: an overview.

PMID- 11231658
TI  - Prognostic importance of myonecrosis after percutaneous coronary interventions.
AB  - Occurrence of myonecrosis can be documented after percutaneous coronary
      interventions (PCI). Data have correlated this phenomenon with late mortality,
      and with diffuse atherosclerotic disease. While controversy still exists, the
      potential for improved mortality after PCI should be fully explored in a
      systematic way.

PMID- 11231659
TI  - Clinical interventional approaches to patients with diffuse coronary artery
      disease.

PMID- 11231660
TI  - Takayasu's arteritis.

PMID- 11231661
TI  - "Hybrid" revascularization: video-thoracoscopy assisted MIDCAB combined with
      angioplasty.
AB  - A "hybrid" revascularization technique has been developed for cases in which a
      chronic total occlusion of the left anterior descending coronary artery (LAD)
      cannot be recanalized by percutaneous coronary intervention, but the lesions in
      the right coronary artery and/or left circumflex artery are very good candidates
      for angioplasty. This technique, which uses video-thoracoscopy assisted minimally
      invasive direct coronary artery bypass to recanalize the occluded LAD and
      angioplasty to dilate favorable lesions in other vessels, would achieve complete
      revascularization in selected patients with multi-vessel disease. In this
      preliminary study of four patients, angioplasty and stenting were successful in
      all patients without any complications; complete revascularization was achieved
      in all 4 patients. No recurrence of angina and no cardiovascular events developed
      during follow-up; this study therefore supports the belief that the "hybrid"
      revascularization technique is both feasible and safe.

PMID- 11231662
TI  - Progress in the management of severe diffuse distal coronary artery disease.

PMID- 11231663
TI  - Association of alcohol use and other high-risk behaviors among trauma patients.
AB  - BACKGROUND: Risk behaviors and psychological problems may limit recovery after
      trauma, may be related to injury recidivism, and may limit the effectiveness of
      alcohol interventions in trauma patients. The aim of the current study was to
      evaluate the prevalence of behaviors associated with injury and their
      relationship with alcohol use in adult trauma patients. METHODS: A prospective
      cohort of 301 adult patients admitted to a single Level I trauma center were
      interviewed regarding risk behaviors and alcohol use. RESULTS: There was evidence
      of acute and/or chronic alcohol use in 48.2% of cases. Over three fourths of
      patients (77%) engaged in one or more high-risk driving practices, 40% engaged in
      one or more violence-related behaviors, and 19% reported suicidal ideation in the
      last year. These risk behaviors were more common in patients who evidenced acute
      and/or chronic alcohol use. CONCLUSION: Behaviors that place an individual at
      greater risk for traumatic injury are common among seriously injured adult
      patients admitted to an urban Level I trauma center and frequently coexist with
      alcohol use. Their importance to injury, injury recidivism, and recovery after
      trauma requires further investigation.

PMID- 11231664
TI  - Do accidents happen accidentally? A study of trauma registry and periodical
      examination database.
AB  - BACKGROUND: Health profile of trauma victims might affect accident involvement.
      Information linking medical data to accident epidemiology is lacking. This study
      aims to identify health factors that increase risk of accident involvement.
      METHODS: The Israeli Defense Forces maintains two databases: records of
      periodical health examination of military personnel and a trauma registry
      including emergency department referrals of personnel resulting from injury. We
      identified 5,578 subjects who were examined in the Periodical Health Examination
      Center and were victims of trauma. We analyzed relation between injuries and
      various health parameters. RESULTS: Results shows cigarette smoking is more
      frequent among the population involved in trauma (40% in motor vehicle crash, 37%
      in fall injury, and 31% in blunt contusion compared with 28% in Periodical Health
      Examination Center population not involved in trauma, p < 0.05). Odds ratio of
      smokers involvement in motor vehicle crash is 1.82 (95% confidence interval, 1.25
      2.67, p < 0.005). Younger age is relatively more frequent among trauma victims.
      CONCLUSION: We conclude that cigarette smokers and younger subjects might be at
      greater risk of being involved in accidental injuries.

PMID- 11231665
TI  - Crash severity, injury patterns, and helmet use in adolescent motorcycle riders.
AB  - BACKGROUND: This study examined crash severity and injury patterns between
      helmeted and unhelmeted adolescent motorcycle riders. METHODS: Among an initial
      population of 4,721 junior college students, 1,284 students were involved in
      1,889 motorcycle crashes during a 20-month follow-up period. Crash severity was
      measured by both the type of collision object and the repair cost of motorcycle
      damage. RESULTS: The incidence rates of crash, injury, hospitalization, and
      deaths per 1,000 person-years in the cohort were 358, 104, 14, and 1.3,
      respectively. Compared with helmeted riders, unhelmeted riders had more
      noncollisions and fewer collisions with a moving car but there was no significant
      difference in repair cost of motorcycle damage between these groups. More
      injuries to the external skin, face, and head and more severe injuries occurred
      in unhelmeted than in helmeted riders. Among crashes resulting in
      hospitalization/death, more injuries to the face and head occurred in unhelmeted
      riders than in helmeted riders. CONCLUSION: Crashes involving unhelmeted riders
      were not more severe but more frequently involved face and head injuries than
      crashes involving helmeted riders.

PMID- 11231666
TI  - Apoptosis in atrophic skeletal muscle induced by brachial plexus injury in rats.
AB  - BACKGROUND: Skeletal muscle atrophy induced by denervation is associated with
      apoptosis. This study was undertaken to determine the role of apoptosis and the
      expression of apoptosis-associated genes in rat skeletal muscle made atrophic by
      brachial plexus injury, and to study the apoptotic signal transduction pathway.
      METHODS: An animal model of skeletal muscle atrophy was established in rats by
      severing the brachial plexus of one forelimb. Apoptosis of muscle cells was
      investigated with terminal deoxynucleotidyl transferase-mediated deoxyuridine
      triphosphate end labeling, flow cytometry, deoxyribonucleic acid (DNA)
      electrophoresis, and electron microscopy. The apoptosis-associated genes Fas,
      FADD, Caspase 8, c-myc, p53, and Bcl-2 were detected by immunohistochemistry and
      Northern blot. RESULTS: By terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate end labeling and flow cytometry we found that the
      percentage of apoptotic muscle cells was higher in atrophic than in healthy
      skeletal muscle (p < 0.05). DNA laddering could be seen in gel electrophoresis of
      DNA from atrophic muscle. By electron microscopy, we observed morphologic change
      of early apoptosis, such as aggregation of chromosomes, expansion of nucleic
      cistern, and contraction of the nucleus. Using immunohistochemistry, we
      determined that in atrophic muscle Fas, FADD, and Caspase-8 genes were highly
      expressed, whereas Bcl-2 was poorly expressed (p < 0.01). However, we did not
      detect a change in the expression of p53 or c-myc genes. Northern blots indicated
      that Fas messenger ribonucleic acid was higher and Bcl-2 messenger ribonucleic
      acid was lower in atrophic than in healthy muscle (p < 0.01). CONCLUSION: There
      are many more apoptotic cells in muscle atrophied as a result of brachial plexus
      injury than in healthy muscle, and apoptosis plays an important role in the
      pathogenesis of atrophy. The apoptotic signal may be transmitted from Fas to FADD
      to Caspase-8, with a decrease in Bcl-2 expression aggravating the process.

PMID- 11231667
TI  - The incidence of combined facial and cervical spine injuries.
AB  - BACKGROUND: The association between facial and cervical spine injuries has been
      documented. However, only severe spinal injuries were included in previous
      analyses. It was the purpose of this study to evaluate the incidence of and risk
      factors for these injury combinations including the complete injury spectrum.
      METHODS: Between 1995 and 1997, 4,907 patients with cervical spine injuries were
      treated at our hospital. One hundred five (2.14%) of these patients had suffered
      a concomitant facial injury. This group was compared with the group of patients
      with cervical spine injury but without facial trauma. RESULTS: The majority of
      cases (98%) consisted of minor lesions to both regions. With increasing severity
      of cervical spine trauma, the risk for facial injury increased. Age and male
      gender represent significant (p < 0.05) risk factors for combined injuries.
      CONCLUSION: Patients sustaining cervical spine trauma have a small but real
      chance of injuring their face as well. The cervical spine must be examined
      carefully, whenever facial injuries are present.

PMID- 11231669
TI  - The functional outcome with metallic radial head implants in the treatment of
      unstable elbow fractures: a long-term review.
AB  - BACKGROUND: A long-term review of metal prosthetic radial head replacement in
      patients with radial head fractures associated with gross instability of the
      elbow has been performed. METHOD: Twenty patients were reviewed using a modified
      Mayo Clinic functional rating index system. The mean follow-up was 12.1 years,
      with a range from 6 to 29 years. RESULTS: Results were excellent in 12 patients,
      good in 4 patients, fair in 2 patients, and poor in 2 patients. A metal radial
      head replacement restored elbow stability when fracture of the radial head
      occurred in combination with dislocation of the elbow, rupture of the medial
      collateral ligament, fracture of the proximal ulna, and/or fracture of the
      coronoid process. CONCLUSION: We conclude that a metal radial head prosthesis has
      select indications. We advocate its use when the radial head cannot be
      reconstructed in the setting of a clinically unstable elbow. Results suggest that
      it functions well on a long-term basis.

PMID- 11231670
TI  - An easy and versatile method of coverage for distal tibial soft tissue defects.
AB  - BACKGROUND: The distally based superficial sural artery flap, first described as
      a distally based neuroskin flap by Masquelet et al., is a skin island flap
      supplied by the vascular axis of the sural nerve. In the difficult area of
      defects in the lower leg and the ankle and heel region, it has a wide variety of
      indications, even in the vascularly compromised patients. It has the largest arc
      of rotation of all flaps that have been described in this region. The most
      important advantage is that it does not compromise a major artery. It is simple
      to dissect and has a low donor morbidity. METHODS: We reported our experience
      with this new flap in 15 cases and also described a new indication for the
      patients with neglected ruptures of the Achilles tendon. RESULTS: In 13 patients,
      the flap was successfully transferred. In two cases, partial necrosis of the flap
      ensued, which healed with secondary intention. CONCLUSION: This flap deserves a
      high degree of interest in the reconstructive armamentarium of the trauma
      surgeon.

PMID- 11231671
TI  - Salvaged limbs after tibial shaft fractures with extensive soft-tissue injury: a
      biopsychosocial function analysis.
AB  - BACKGROUND: The purpose of this study was to perform a biopsychosocial function
      analysis of the outcome in patients with a salvaged leg after tibial shaft
      fractures associated with extensive soft-tissue injury. METHODS: A retrospective
      review of 18 consecutive patients with tibial shaft fractures and extensive soft
      tissue damage with a mean Injury Severity Score of 31 was undertaken. All
      patients were assessed for their physical function, psychological status, and
      general function. RESULTS: The range of motion and torque of the ankle joint were
      severely affected. The knee joint was affected, but only with regard to the
      torque during concentric muscular activities. Nottingham Health Profile scores
      showed that the general and social function for these patients were significantly
      affected. Five of 18 patients suffered from depression. CONCLUSION: Salvage
      procedures should be advocated if possible, but careful selection of patients on
      the basis of mental and social factors is crucial for the outcome.

PMID- 11231672
TI  - Reaming debris in osteotomized sheep tibiae.
AB  - BACKGROUND: Reamed nailing gives better fracture healing than unreamed nailing in
      operative treatment of fractures and nonunions. This study investigates the
      effect of isolated reaming debris on fracture healing in an animal model.
      METHODS: Thirty sheep were treated with an osteotomy of the tibia with 5-mm
      distraction. In one group, the osteotomy gap was left empty; in the second group,
      the gap was packed with reaming debris from the ipsilateral femur; and in the
      third group, the gap was packed with cancellous bone from the iliac crest. At
      follow-up, callus volume was measured on standard radiographs. RESULTS: After 3
      weeks, callus volume from the reaming debris group as well as the iliac crest
      group had increased significantly compared with the empty group. CONCLUSION: This
      study shows that isolated reaming debris supports callus building as much as
      conventional bone grafting, which might explain why fractures heal with more
      callus formation when treated with reamed nailing compared with unreamed nailing.

PMID- 11231673
TI  - Peroneus brevis tendon transfer in neglected tears of the Achilles tendon.
AB  - BACKGROUND: We present the results of a single-center, single-surgeon study in 59
      patients with a fresh (4 women and 23 men; mean age, 43.6 +/- 8.8 years) or a
      neglected (1 woman and 21 men; mean age, 41.3 +/- 7.4 years) Achilles tendon
      rupture. METHODS: Patients with a fresh rupture were operated on using end-to-end
      suture, and patients with a neglected rupture received the tendon of the peroneus
      brevis as an autologous graft. Patients were assessed during the sixth
      postoperative week, and during the sixth postoperative month. They were
      discharged within 1 year after the operation, and were reviewed at an average of
      53 +/- 13 months after surgery. RESULTS: Patients were generally satisfied with
      the procedure, but those with a neglected rupture tended to have a greater
      postoperative complication rate, greater loss of isokinetic strength variables at
      high speeds, and greater loss of calf circumference. CONCLUSION: The management
      of acute and neglected subcutaneous tears of the Achilles tendon by peroneus
      tendon transfer is safe but technically demanding. It affords good recovery, even
      in patients with a neglected rupture of 6 weeks' to 9 months' duration. Patients
      with a neglected rupture are at a slightly greater risk of postoperative
      complications, and their ankle plantar flexion strength can be reduced.

PMID- 11231674
TI  - Ocular complications of thermal injury: a 3-year retrospective.
AB  - BACKGROUND: Diagnosis and treatment of thermal ocular injuries are often delayed
      because facial burns are usually associated with life-threatening injuries
      requiring immediate intervention. The purpose of the present study is to review
      the diagnosis and management of ocular complications associated with thermal
      burns in a tertiary care burn unit. METHODS: In this retrospective study, the
      charts of patients admitted to the Loyola University Medical Center Burn Unit
      between January 1993 and January 1996 were reviewed. RESULTS: Of the 1,461
      patients who were admitted to the burn unit during that period, 155 (10.6%)
      required ophthalmic consultation. Sixty-one patients (4.2%) had ocular injury,
      the most common type being periorbital burn and edema followed by corneal
      involvement. Thirty-one of the 61 patients (51%) received consultation on the day
      of admission. Six of the 61 patients (10%) required surgical intervention. There
      was no correlation between number of days to consultation and need for surgical
      intervention. Patients requiring surgery were more likely to have suffered third
      degree burns. CONCLUSION: Because it is difficult to predict which patients
      suffering from thermal burns involving the eyes will require surgical
      intervention, ophthalmic consultation should be sought early.

PMID- 11231675
TI  - Different hypotensive responses to intravenous bovine and human thrombin
      preparations in swine.
AB  - BACKGROUND: Accidental intravenous introduction of commercial bovine thrombin
      (BT) during use of fibrin glue may result in profound hypotension. Commercial
      human thrombin (HT) is now available. This study compared the effects of
      intravenous BT versus HT in swine. METHODS: Swine received 30 U/kg BT, 60 U/kg
      BT, 30 U/kg HT, or 60 U/kg HT intravenously. Mean arterial pressure (MAP) and
      survival were monitored for 30 minutes. Thrombin purities and in vitro activities
      were examined. RESULTS: MAP nadir was lower (p < 0.05) after BT, 27.7 +/- 3.3%
      (mean +/- SEM) of pretreatment MAP, compared with 41.1 +/- 3.7% after HT. Five of
      six animals died after 60 U/kg BT, whereas all others survived (p < 0.05).
      Histology suggested more severe disseminated intravascular coagulation after BT.
      HT was purer than BT. In vitro activities were similar. CONCLUSION: Both BT and
      HT produced hypotension. HT appeared safer, because of higher purity. Regardless
      of source and purity, thrombin must be used with caution.

PMID- 11231676
TI  - The impact of major in-hospital complications on functional outcome and quality
      of life after trauma.
AB  - BACKGROUND: Little is known about the impact of major in-hospital complications
      on functional outcome in the short- and long-term period after serious injury.
      The Trauma Recovery Project (TRP) is a large, prospective, epidemiologic study
      designed to examine multiple outcomes after major trauma, including quality of
      life and functional limitation. Patient outcomes were assessed at discharge and
      at 6, 12, and 18 months after discharge. The specific objectives of the present
      report are to examine the effect of postinjury complications on functional
      outcomes at discharge and at 6-, 12-, and 18-month follow-up time points in the
      TRP population. METHODS: Between December 1, 1993, and September 1, 1996, 1,048
      eligible trauma patients triaged to four participating trauma center hospitals in
      the San Diego Regionalized Trauma System were enrolled in the study. The
      enrollment criteria for the study included age 18 years or older; admission
      Glasgow Coma Scale score of 12 or greater; and length of stay greater than 24
      hours. Quality of life was measured after injury using the Quality of Well-being
      (QWB) scale, a sensitive index to the well end of the functioning continuum
      (range, 0 [death] to 1.000 [optimum functioning]). Major in-hospital
      complications were assessed for 820 patients and were coded as pulmonary,
      cardiovascular, gastrointestinal, hepatic, hematologic, infections, renal,
      musculoskeletal, neurologic, and vascular, on the basis of standardized codes
      used in the Trauma Registry. RESULTS: Major in-hospital complications were
      present in 83 (10.1%) patients. Discharge QWB scores were significantly lower in
      patients with major complications (0.394 vs. 0.402, p < 0.05). QWB scores were
      also significantly lower at 6-month follow-up in patients with major
      complications (0.575 vs. 0.637, p < 0.0001). Types of major complications with
      significantly lower 6-month follow-up QWB scores were pulmonary,
      gastrointestinal, infections, and musculoskeletal. Patients with major
      complications also had significantly lower 12-month (0.626 vs. 0.674, p < 0.01)
      and 18-month (0.646 vs. 0.681, p < 0.05) follow-up QWB scores. Pulmonary major
      complications and infections were associated with significantly lower QWB scores
      at 12-month follow-up. CONCLUSION: These results provide new evidence that major
      in-hospital complications may have an important impact on functional outcomes
      after major trauma.

PMID- 11231677
TI  - Do pediatric trauma centers have better survival rates than adult trauma centers?
      An examination of the National Pediatric Trauma Registry.
AB  - BACKGROUND: Pediatric trauma centers (PTCs) were developed to improve the
      survival of injured children, but it is currently unknown if children admitted to
      PTCs are more likely to survive than those admitted to adult trauma centers
      (ATCs). METHODS: Fifty-three thousand one hundred thirteen pediatric trauma cases
      from 22 PTCs and 31 ATCs included in the National Pediatric Trauma Registry were
      reviewed to evaluate survival rates at PTCs and ATCs. RESULTS: Overall, 1,259
      children died. The raw mortality rate was lower at PTCs (1.81% of 32,554
      children) than at ATCs (3.88% of 18,368 children). However, patients admitted to
      ATCs were more severely injured. When Injury Severity Score, Pediatric Trauma
      Score, mechanism (blunt or penetrating), gender, age, clustering, and American
      College of Surgeons (ACS) verification status were controlled for using a single
      logistic regression model, there was no statistically significant difference in
      survival between PTCs and ATCs (odds ratio, 1.02; 95% confidence interval, 0.83
      1.26; p = 0.587). A similar comparison of the 12 ACS-verified trauma centers with
      the 41 nonverified centers showed verification to be associated with improved
      survival (odds ratio, 0.75; 95% confidence interval, 0.58-0.97; p = 0.013).
      CONCLUSION: Although PTCs have higher overall survival rates than ATCs, this
      difference disappears when the analysis controls for Injury Severity Score,
      Pediatric Trauma Score, age, mechanism, and ACS verification status. ACS-verified
      centers have significantly higher survival rates than do unverified centers.

PMID- 11231679
TI  - 2,576 ultrasounds for blunt abdominal trauma.
AB  - BACKGROUND: Determination of intra-abdominal injury following blunt abdominal
      trauma (BAT) continues to be a diagnostic challenge. Ultrasound (US) has been
      described as a potentially useful diagnostic tool in this setting and is being
      used with increasing frequency in trauma centers. We determined the diagnostic
      capability of US in the evaluation of BAT. METHODS: A retrospective analysis of
      our trauma US database was performed over a 30-month period. Computed tomographic
      scan, diagnostic peritoneal lavage, or exploratory laparotomy confirmed the
      presence of intra-abdominal injury. RESULTS: During the study period, 8,197
      patients were evaluated at the Ryder Trauma Center. Of this group, 2,576 (31%)
      had US in the evaluation of BAT. Three hundred eleven (12%) US exams were
      considered positive. Forty-three patients (1.7%) had a false-negative US; of this
      group, 10 (33%) required exploratory laparotomy. US had a sensitivity of 86%, a
      specificity of 98%, and an accuracy of 97% for detection of intra-abdominal
      injuries. Positive predictive value was 87% and negative predictive value was
      98%. CONCLUSION: Emergency US is highly reliable and may replace computed
      tomographic scan and diagnostic peritoneal lavage as the initial diagnostic
      modality in the evaluation of most patients with BAT.

PMID- 11231678
TI  - Enhanced expression of heat shock proteins in leukocytes from trauma patients.
AB  - BACKGROUND: Heat shock proteins (HSPs) play essential roles as molecular
      chaperones in cells to assist in the repair of degenerated proteins. The
      expression of HSPs in polymorphonuclear leukocytes (PMNLs) following insult has
      not been delineated. The objective of this study was to clarify the serial
      changes in HSP expression in PMNLs from trauma patients. METHODS: Fifty severely
      injured patients (mean Injury Severity Score of 31.8 +/- 10.8) and 17 healthy
      volunteers were included as study subjects. Blood samples were serially obtained
      at three time points: days 0 to 1, days 2 to 5, and days 6 to 14 after the trauma
      event. We measured expressions of HSP27, HSP60, HSP70, and HSP90 in permeabilized
      PMNLs by flow cytometry using a monoclonal antibody generated against each HSP
      and fluorescein isothiocyanate-conjugated antimouse immunoglobulins as secondary
      reagents. We also evaluated the expression of HSP70 mRNA in PMNLs by Northern
      blot hybridization and the expression of HSP70 in PMNLs by fluorescence
      microscopy. RESULTS: Expressions of HSP27, HSP70, and HSP90 in PMNLs from trauma
      patients were significantly greater than in PMNLs from healthy volunteers in all
      three periods (days 0-1, days 2-5, and days 6-14). The expression of HSP60 in
      PMNLs from trauma patients was significantly greater than normal expression on
      days 2 to 5 and days 6 to 14. The values for HSP27, HSP60, and HSP70 on days 2 to
      5 were significantly higher than those on days 0 to 1. The expression of HSP70
      mRNA in PMNLs was significantly enhanced for as long as 2 weeks after trauma
      compared with that in normal volunteers. CONCLUSION: Severe trauma causes
      demonstrated enhanced expression of HSPs in PMNLs during the acute phase. This
      enhanced expression of HSPs may regulate PMNL functions.

PMID- 11231680
TI  - Fatal blunt aortic injuries: a review of 242 autopsy cases.
AB  - OBJECTIVE: To characterize fatal blunt aortic injury (BAI). METHODS: A
      retrospective chart review of 242 cases of fatal BAI in patients who underwent an
      autopsy at our institution between 1984 and 1997 was performed. Comparisons were
      made for statistical differences using the z-test. RESULTS: Two hundred forty-two
      cases of fatal BAI were reviewed, making this the largest BAI autopsy study to
      date. Mechanisms of BAI included driver/passenger in motor vehicle crash (MVC)
      (68%), pedestrian versus MVC (17%), and motorcycle crash (8%). When comparing the
      mechanisms in the time period 1984 to 1988 to the time period 1989 to 1997, only
      the pedestrian versus MVC mechanism was significantly different (12% vs. 23%, p <
      0.05). MVC direction of impact included head-on (45%), lateral (35%), and complex
      (20%). Two thirds of the victims sustained head injuries, rib fractures, and/or
      hepatic trauma. Only 58% of the victims had the classic isthmus laceration. There
      was one preventable death secondary to delay in diagnosis. CONCLUSION: BAI is not
      limited to frontal impact crashes; there should be a high index of suspicion of
      BAI in lateral impact crashes as well as pedestrian versus MVC mechanisms.
      Nonisthmus and complex aortic lacerations are common in fatal BAI. Finally, BAI
      is a highly lethal injury with few preventable deaths in this series.

PMID- 11231681
TI  - Geriatric falls: injury severity is high and disproportionate to mechanism.
AB  - OBJECTIVE: Falls are a well-known source of morbidity and mortality in the
      elderly. Fall-related injury severity in this group, however, is less clear,
      particularly as it relates to type of fall. Our purpose is to explore the
      relationship between mechanism of fall and both pattern and severity of injury in
      geriatric patients as compared with a younger cohort. METHODS: Our trauma
      registry was queried for all patients evaluated by the trauma service over a 412
      year period (1994-1998). Two cohorts were formed on the basis of age greater than
      65 or less than or equal to 65 years and compared as to mechanism, Injury
      Severity Score (ISS), Abbreviated Injury Scale score, and mortality. RESULTS:
      Over the study period, 1,512 patients were evaluated, 333 greater than 65 years
      and 1,179 less than or equal to 65 years of age. Falls were the injury mechanism
      in 48% of the older group and 7% of the younger group (p < 0.05). Falls in the
      older group constituted 65% of patients with ISS >15, with 32% of all falls
      resulting in serious injury (ISS >15). In contrast, falls in the younger group
      constituted only 11% of ISS >15 patients, with falls causing serious injury only
      15% of the time (both p < 0.05). Notably, same-level falls resulted in serious
      injury 30% of the time in the older group versus 4% in the younger group (p <
      0.05), and were responsible for an ISS >15 30-fold more in the older group (31%
      vs. <1%; p < 0.05). Abbreviated Injury Scale evaluation revealed more frequent
      head/neck (47% vs. 22%), chest (23% vs. 9%), and pelvic/extremity (27% vs. 15%)
      injuries in the older group for all falls (all p < 0.05). The mean ISS for same
      level falls in the older group was twice that for the younger group (9.28 vs.
      4.64, p < 0.05), whereas there was no difference in mean ISS between multilevel
      and same-level falls within the older group itself (10.12 vs. 9.28, p > 0.05).
      The fall-related death rate was higher in the older group (7% vs. 4%), with falls
      seven times more likely to be the cause of death compared with the younger group
      (55% vs. 7.5%) (both p < 0.05). Same-level falls as a cause of death was 10 times
      more common in the elderly (25% vs. 2.5%, p < 0.05). CONCLUSION: Falls among the
      elderly, including same-level falls, are a common source of both high injury
      severity and mortality, much more so than in younger patients. A different
      pattern of injury between older and younger fall patients also exists.

PMID- 11231682
TI  - Localized autonomic abnormality: another clinical marker of blunt cervical
      vascular injury?

PMID- 11231683
TI  - Gunshot wound to the head resulting in a vertebral artery pseudoaneurysm at the
      base of the skull.

PMID- 11231684
TI  - Intraluminal shunt placement and off-pump coronary revascularization for coronary
      artery stab wound.

PMID- 11231685
TI  - False aneurysm of the thoracic aorta associated with an aorto-chest wall fistula
      after spinal instrumentation.

PMID- 11231686
TI  - Traumatic pneumothorax ex vacuo.

PMID- 11231687
TI  - Thoracic splenosis 25 years after gunshot wound to the abdomen.

PMID- 11231688
TI  - Chronic knee fracture dislocation treated by the Ilizarov technique: case report.

PMID- 11231689
TI  - A new type of triplane fracture in a 19-year-old snowboarder.

PMID- 11231690
TI  - Intrathecal baclofen after traumatic brain injury: early treatment using a new
      technique to prevent spasticity.
AB  - BACKGROUND: In the early course of severe head trauma, the clinical value of
      intrathecal administration of baclofen to reduce autonomic disorders and
      spasticity has not been established. METHODS: We studied four patients (Glasgow
      Coma Scale score 3 or 4) with autonomic disorders and spasticity who failed to
      respond to conventional treatment during the early course of head injury.
      Baclofen (25 microg/mL) was infused continuously through an intrathecal catheter
      inserted at patient bedside and subcutaneously tunneled. When this treatment was
      successful, the spinal catheter was removed and surgically replaced by another
      catheter connected to a subcutaneous pump. Clinical follow-up was obtained at 6
      months after the head injury. RESULTS: Mean delay for the initiation of
      intrathecal baclofen was 25 days (range, 21 to 31 days), and optimal dose was 385
      +/- 185 microg/day. In all patients, the Ashworth score was consistently reduced
      (3.5 +/- 0.5 vs. 4.5 +/- 0.5 for upper limbs and 2 +/- 0.5 vs. 4.5 +/- 0.5 for
      lower limbs), as were both the frequency and intensity of autonomic disorders.
      The spinal catheters were used during a mean period of 9.5 +/- 1.7 days without
      complications. All three survivors were equipped with a programmable pump and had
      a lower Ashworth score at 6 months. Autonomic disorders had disappeared in two
      patients and remained modest in the remaining patient. CONCLUSION: Continuous
      administration of baclofen via the intrathecal route using this new technique
      seems to reduce autonomic disorders and spasticity during the early course of
      severe traumatic head injury.

PMID- 11231691
TI  - Extraterrestrial resuscitation of hemorrhagic shock: fluids.

PMID- 11231692
TI  - Underwater explosion lung injury.

PMID- 11231693
TI  - Postinjury torso ultrasound: FAST should be SLOH.

PMID- 11231694
TI  - Findings from the 1995 Cuyahoga County Trauma Registry and Trauma Foundation of
      Northeast Ohio (TFNO).

PMID- 11231695
TI  - The itch to write (a personal account).

PMID- 11231696
TI  - Environmental and drug effects on patients with pacemakers and implantable
      cardioverter/defibrillators: a practical guide to patient treatment.

PMID- 11231697
TI  - Physicians' responses to patients' requests for physician-assisted suicide.
AB  - BACKGROUND: Studies show that patient requests for physician-assisted suicide
      (PAS) are a relatively common clinical occurrence. The purpose of this study was
      to describe how experienced physicians assess and respond to requests for
      assisted suicide. METHODS: Focused ethnography in the offices of 11 acquired
      immunodeficiency syndrome physicians, 8 oncologists, and 1 hospice physician who
      had received requests for assisted suicide in their practice. Ten had facilitated
      PAS. RESULTS: Informants had a similar approach to evaluating patients who
      requested assisted suicide, often asking, "Why do you want to die now?" Reasons
      for requests fell into 3 broad categories: physical symptoms, psychological
      issues, and existential suffering. Physicians thought they competently addressed
      patients' physical symptoms, and this obviated most requests. They treated
      depression empirically and believed they did not assist depressed patients with
      assisted suicide. Physicians had difficulty addressing patients' existential
      suffering, which led to most facilitated requests. Informants rarely talked to
      colleagues about requests for assisted suicide, suggesting a "professional code
      of silence." CONCLUSIONS: Regardless of divergent attitudes about PAS, physicians
      respond similarly to requests for assisted suicide from their patients, creating
      a common ground for professional dialogue. Our sample addressed physical
      suffering aggressively, treated depression empirically, but struggled with
      requests arising from existential suffering. A professional code of silence
      regarding PAS creates professional isolation. Clinicians do not share knowledge
      or receive social support from peers about their decisions regarding assisted
      suicide. Educational strategies drawing on approaches used by experienced
      clinicians may create an atmosphere that enables physicians with divergent
      beliefs to discuss this difficult subject.

PMID- 11231698
TI  - The role of angiotensin receptor blockers in the management of chronic heart
      failure.
AB  - Clinical and basic science research has repeatedly confirmed the importance of
      the renin-angiotensin-aldosterone system in the pathophysiology of chronic heart
      failure. Accordingly, blockade of this system by angiotensin-converting enzyme
      (ACE) inhibitors has assumed a central role in the treatment of heart failure.
      Recently, angiotensin II receptor blockers (ARBs) have gained prominence as a
      possible substitute for ACE inhibitors in therapy for heart failure. However,
      clinical data compiled on this use of ARBs have shown them to be useful only as
      alternative therapy in ACE inhibitor-intolerant patients. Continuing large-scale
      clinical investigations may lead to an expansion of their role in therapy for
      various cardiovascular diseases.

PMID- 11231699
TI  - New approaches to diagnosis and management of unstable angina and non-ST-segment
      elevation myocardial infarction.
AB  - Recently, it has been demonstrated in multiple clinical research studies that non
      Q-wave myocardial infarction shares many of the features of unstable angina
      pectoris and that both diseases initially are managed similarly. Important new
      antiplatelet drugs (glycoprotein IIb-IIIa inhibitors) and antithrombin agents
      (low-molecular-weight heparin) are currently recommended for patients with
      unstable angina pectoris/non-ST-segment elevation MI who are at high or
      intermediate risk on the basis of symptoms, electrocardiographic findings, and
      the presence or absence of serum markers (eg, troponin I, troponin T, and
      creatine kinase-MB). This review provides important information concerning the
      results of clinical studies of glycoprotein IIb-IIIa inhibitors (tirofiban
      hydrochloride and eptifibatide) when used with unfractionated heparin in patients
      with this syndrome or with low-molecular weight heparin (enoxaparin sodium) in
      similar patients. The Thrombolysis in Myocardial Infarction IIIB, Veterans
      Affairs Non-Q-Wave Infarction Studies in Hospital, and Fast Revascularization
      During Instability in Coronary Artery Disease II studies evaluating a
      conservative, ischemia-guided approach vs an early aggressive approach to such
      patients are presented, with a practical algorithm for treating such patients.

PMID- 11231700
TI  - Effects of reduced sodium intake on hypertension control in older individuals:
      results from the Trial of Nonpharmacologic Interventions in the Elderly (TONE).
AB  - BACKGROUND: Few trials have evaluated the effects of reduced sodium intake in
      older individuals, and no trial has examined the effects in relevant subgroups
      such as African Americans. PATIENTS AND METHODS: The effects of sodium reduction
      on blood pressure (BP) and hypertension control were evaluated in 681 patients
      with hypertension, aged 60 to 80 years, randomly assigned to a reduced sodium
      intervention or control group. Participants (47% women, 23% African Americans)
      had systolic BP less than 145 mm Hg and diastolic BP less than 85 mm Hg while
      taking 1 antihypertensive medication. Three months after the start of
      intervention, medication was withdrawn. The primary end point was occurrence of
      an average systolic BP of 150 mm Hg or more, an average diastolic BP of 90 mm Hg
      or more, the resumption of medication, or a cardiovascular event during follow-up
      (mean, 27.8 months). RESULTS: Compared with control, mean urinary sodium
      excretion was 40 mmol/d less in the reduced sodium intervention group (P<.001);
      significant reductions in sodium excretion occurred in subgroups defined by sex,
      race, age, and obesity. Prior to medication withdrawal, mean reductions in
      systolic and diastolic BPs from the reduced sodium intervention, net of control,
      were 4.3 mm Hg (P<.001) and 2.0 mm Hg (P =.001). During follow-up, an end point
      occurred in 59% of reduced sodium and 73% of control group participants (relative
      hazard ratio = 0.68, P<.001). In African Americans, the corresponding relative
      hazard ratio was 0.56 (P =.005); results were similar in other subgroups. In dose
      response analyses, end points were progressively less frequent with greater
      sodium reduction (P for trend =.002). CONCLUSION: A reduced sodium intake is a
      broadly effective, nonpharmacologic therapy that can lower BP and control
      hypertension in older individuals.

PMID- 11231701
TI  - Randomized trial of folic acid supplementation and serum homocysteine levels.
AB  - BACKGROUND: Lowering serum homocysteine levels with folic acid is expected to
      reduce mortality from ischemic heart disease. Homocysteine reduction is known to
      be maximal at a folic acid dosage of 1 mg/d, but the effect of lower doses
      (relevant to food fortification) is unclear. METHODS: We randomized 151 patients
      with ischemic heart disease to 1 of 5 dosages of folic acid (0.2, 0.4, 0.6, 0.8,
      and 1.0 mg/d) or placebo. Fasting blood samples for serum homocysteine and serum
      folate analysis were taken initially, after 3 months of supplementation, and 3
      months after folic acid use was discontinued. RESULTS: Median serum homocysteine
      level decreased with increasing folic acid dosage, to a maximum at 0.8 mg of
      folic acid per day, when the homocysteine reduction (placebo adjusted) was 2.7
      micromol/L (23%), similar to the known effect of folic acid dosages of 1 mg/d and
      above. The higher a person's initial serum homocysteine level, the greater was
      the response to folic acid, but there were statistically significant reductions
      regardless of the initial level. Serum folate level increased approximately
      linearly (5.5 nmol/L for every 0.1 mg of folic acid). Within-person fluctuations
      over time in serum homocysteine levels, measured in the placebo group, were large
      compared with the effect of folic acid, indicating that monitoring of the
      reduction in an individual is impractical. CONCLUSIONS: A dosage of folic acid of
      0.8 mg/d appears necessary to achieve the maximum reduction in serum homocysteine
      level across the range of homocysteine levels in the population. Current US food
      fortification levels will achieve only a small proportion of the achievable
      homocysteine reduction.

PMID- 11231702
TI  - Cardiovascular disease in the Adventures of Sherlock Holmes.
AB  - The Adventures of Sherlock Holmes by Sir Arthur Conan Doyle contains many
      incidents of medical interest. While disorders of the cardiovascular system do
      not play an important role in these tales, there are, nevertheless, some
      illnesses that invite speculation. Eleven such incidents are reviewed and
      discussed in light of the times in which they occurred and in light of current
      medical knowledge.

PMID- 11231703
TI  - How much information about adverse effects of medication do patients want from
      physicians?
AB  - BACKGROUND: Little information exists concerning the amount of information
      patients expect from physicians as to the risk for an adverse medication
      reaction. The present study was designed to determine such opinions in a
      population sample; to correlate results with sex, age, educational level, and
      previous experience with adverse effects; and to determine whether patients
      believe physicians should use discretion in the amount of such information given.
      METHODS: Two thousand five hundred sequential adults visiting outpatient clinics
      filled out a 12-item questionnaire. Percentages of subjects desiring information
      about varying degrees of risk and those believing physicians should and should
      not use discretion in the amount of such information provided were recorded.
      Results were correlated with demographic variables and previous experience of
      adverse effects. RESULTS: Among the respondents, 76.2% desired to be told of all
      possible adverse effects; 13.3% only if an adverse effect occurred 1 in 100 000
      times; and 10.2% only if such occurrence was 1 in 100 times; 0.4% were not
      interested in any information. (Percentages have been rounded and do not total
      100.) Percentages were closely similar to those for the same question that
      restricted opinion to serious adverse effects. Desire for maximum information was
      significantly correlated with lower educational level (P<.00l) and previous
      frequent experience with adverse effects (P<.001) and in older women (P<.001).
      The opinion that the physician should give the same information to all patients
      was given by 67.6% of the sample, and 73.4% opined that physicians were never
      justified in withholding any information. CONCLUSION: Most individuals desire
      from physicians all information concerning possible adverse effects of prescribed
      medication and do not favor physician discretion in these decisions.

PMID- 11231704
TI  - Treatment of 193 episodes of laryngeal edema with C1 inhibitor concentrate in
      patients with hereditary angioedema.
AB  - BACKGROUND: Hereditary angioedema (HAE) is an autosomal dominant disease
      (Mendelian Inheritance in Man 106100) caused by an inherited deficiency of C1
      inhibitor (C1-INH) function. The clinical symptoms include skin swelling,
      abdominal pain, and life-threatening episodes of upper airway obstruction. We
      evaluated the efficacy of C1-INH concentrate for treating sudden airway
      compromise. METHODS: A series of 95 patients with HAE and a functional deficiency
      of C1-INH belonging to 59 families underwent screening for laryngeal edema.
      Double-blind treatment of randomized patients was not justifiable because of the
      life-threatening nature of this condition. Efficacy was evaluated by determining
      the interval from injection of C1-INH concentrate to the beginning of resolution
      of symptoms. The mean duration of episodes of laryngeal edema was compared in
      treated and untreated patients. Clinical information was obtained from emergency
      department physicians, the hospitals involved, reports of the general
      practitioners, and patients and their relatives. RESULTS: Forty-two patients had
      517 episodes of laryngeal edema. Eighteen patients received 500- or 1000-U
      injections of C1-INH concentrate in 193 episodes. The C1-INH concentrate was
      effective in all laryngeal edemas. The interval from injection to interruption in
      progress of symptoms ranged from 10 minutes to 4 hours (mean +/- SD, 42.2 +/-
      19.9 minutes). The mean +/- SD duration of laryngeal edema was 15.3 +/- 9.3 hours
      in patients who received C1-INH concentrate and 100.8 +/- 26.2 hours in those who
      did not. CONCLUSIONS: Injected C1-INH concentrate is highly and rapidly effective
      in the treatment of laryngeal edema of HAE. Relief and resolution of symptoms
      begins 30 to 60 minutes after injection, and duration of the upper airway
      obstruction is substantially reduced.

PMID- 11231705
TI  - Early switch and early discharge strategies in patients with community-acquired
      pneumonia: a meta-analysis.
AB  - BACKGROUND: The effectiveness of early switch and early discharge strategies in
      patients with community-acquired pneumonia remains unknown. METHODS: We searched
      the MEDLINE, HEALTHSTAR, EMBASE, Cochrane Collaboration, and Best Evidence
      databases from January 1, 1980, to March 31, 2000, for community-acquired
      pneumonia studies that included specific switch criteria or recommendations to
      switch on a particular day. RESULTS: From 1794 titles identified, 121 articles
      were reviewed. We identified 10 prospective, interventional, community-acquired
      pneumonia-specific studies that evaluated length of stay (LOS). Nine studies
      applied an early switch from parenteral to oral antibiotic criteria. Six
      different criteria for switching were applied in the 9 studies. Five of the
      studies that applied early switch criteria also applied separate criteria for
      early discharge. Six studies applied an early switch and early discharge strategy
      to an intervention and control group, and 5 of these provided SD values for LOS.
      The mean change in LOS was not significantly (P =.05) reduced in studies of early
      switch and early discharge (-1.64 days; 95% confidence interval, -3.30 to 0.02
      days). However, when the 2 studies in which the recommended LOS was longer than
      the control LOS were excluded from the analysis, the mean change in LOS was
      reduced by 3 days (-3.04 days; 95% confidence interval, -4.90 to -1.19 days).
      Studies did not reveal significant differences in clinical outcomes between the
      intervention and control groups. CONCLUSIONS: There is considerable variability
      in early switch from parenteral to oral antibiotic criteria for patients with
      community-acquired pneumonia. Early switch and early discharge strategies may
      significantly and safely reduce the mean LOS when the recommended LOS is shorter
      than the actual LOS.

PMID- 11231706
TI  - Are aneroid sphygmomanometers accurate in hospital and clinic settings?
AB  - BACKGROUND: The aneroid sphygmomanometer is commonly used for the indirect
      measurement of blood pressure despite significant concerns about its accuracy.
      Although the mercury sphygmomanometer is highly accurate, there are concerns
      about the environmental toxicity of mercury. In response to various external
      pressures to become essentially mercury free, the Mayo Clinic, Rochester, Minn,
      has replaced many mercury sphygmomanometers with aneroid devices. Since 1993, a
      maintenance protocol has been in place to ensure proper function and accuracy of
      these devices. METHODS: We assessed the accuracy of 283 aneroid devices using as
      the reference standard a digital pressure and vacuum meter that was calibrated
      using a mercury sphygmomanometer. RESULTS: The mean +/- SD values from the
      aneroid device in millimeters of mercury at each reference point (at 20-mm Hg
      intervals from 60 to 240 mm Hg defined by the reference device) were 59.9 +/- 1.9
      at 60; 79.9 +/- 1.9 at 80; 100.0 +/- 1.8 at 100; 120.3 +/- 1.8 at 120; 140.7 +/-
      1.4 at 140; 160.7 +/- 1.7 at 160; 180.9 +/- 1.3 at 180; 200.7 +/- 5.0 at 200;
      221.0 +/- 1.3 at 220; and 240.8 +/- 1.6 at 240 (r = 0.99; P<.001). The values
      from the aneroid device underestimated those of the reference device by a mean of
      0.5 mm Hg (95% confidence interval, 0.3-0.7). Virtually 100% of the values from
      the aneroid device were within the 4-mm Hg range recommended by the Association
      for the Advancement of Medical Instrumentation. CONCLUSION: Aneroid
      sphygmomanometers provide accurate pressure measurements when a proper
      maintenance protocol is followed.

PMID- 11231707
TI  - Baseline oxygen saturation predicts exercise desaturation below prescription
      threshold in patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Recent studies of exercise-induced hypoxemia in patients with chronic
      obstructive pulmonary disease (COPD) have shown that oxygen supplementation
      during exertion increases exercise tolerance and alleviates dyspnea. Although
      measurements of forced expiratory volume in 1 second and diffusion capacity for
      carbon monoxide (DLCO) are known to predict exercise-induced desaturation in
      patients with COPD, baseline oxygen saturation has never been studied as a
      predictor of exercise-induced desaturation. METHODS: A retrospective analysis was
      performed of 100 consecutive patients with forced expiratory volume in 1 second
      forced vital capacity ratio of 70% or less who underwent exercise testing for
      desaturation. Any desaturation to 88% or less with exercise was considered
      significant. Nineteen patients with total lung capacity of 80% or less were
      excluded to avoid evaluating those with combined obstructive and restrictive
      defects; 81 patients remained available for study. RESULTS: Nineteen (51%) of 37
      patients with resting saturation of 95% or less desaturated with exercise as
      opposed to 7 (16%) of 44 with resting saturation of 96% or greater (P =.001). The
      sensitivity and the negative predictive value of baseline saturation of 95% or
      less as a screening test for exercise desaturation were 73% and 84%,
      respectively. If all patients with DLCO of 36% or less were excluded, 40 patients
      were left for study. Eight (40%) of 20 patients with baseline saturation of 95%
      or less compared with 0 of 20 with resting saturation of 96% or greater
      desaturated with exercise (P =.006). In this subset, the sensitivity and the
      negative predictive value of baseline saturation of 95% or less as a screening
      test for exercise desaturation both improved to 100%. CONCLUSIONS: In patients
      with COPD, baseline saturation of 95% or less is a good screening test for
      exercise desaturation, especially in patients with DLCO greater than 36%. This
      readily available office screening procedure merits further study in larger
      prospective patient cohorts.

PMID- 11231708
TI  - Urban-rural differences in the quality of care for medicare patients with acute
      myocardial infarction.
AB  - BACKGROUND: There are urban-rural differences in health care utilization in
      Kansas. This study was conducted to determine if similar differences exist in the
      quality of inpatient care provided for patients with acute myocardial infarction
      (AMI). METHODS: All acute care hospitals in the state were stratified into 12
      urban, 31 semirural, and 76 rural hospitals according to their location. Data
      from medical records of 2521 Medicare patients 65 years and older who had
      survived AMI and were discharged alive from hospitals during an 8-month period in
      1994/1995 were abstracted. The measures of the quality of care (quality
      indicators [QIs]) were the use of aspirin (during hospital stay and at discharge)
      and the administration of beta-blockers, intravenous (IV) nitroglycerin, heparin,
      and reperfusion by thrombolytic therapy or primary angioplasty. RESULTS: A
      significantly higher proportion of ideal candidates for the use of aspirin during
      hospital stay and at discharge, heparin, and IV nitroglycerin received these
      medications in urban hospitals, and a lower proportion of similar patients
      received these medications in rural hospitals compared with the patients in
      semirural hospitals (P<.001). Similar trends in each of the 6 QIs were observed
      for less than ideal patients (P<.05). Patient age was associated with a
      relatively poor quality of care in terms of the 6 QIs. Except for the
      administration of IV nitroglycerine to less than ideal patients, age adjustments
      did not change the observed urban-rural differences in the QI measures.
      CONCLUSION: Relatively poor quality of care for patients with AMI was provided by
      rural hospitals where greater opportunity for improvement exists.

PMID- 11231709
TI  - The adequacy of informed consent for placement of gastrostomy tubes.
AB  - BACKGROUND: Gastrostomy tubes are placed commonly in patients with limited life
      expectancy. However, it is unclear whether the process of informed consent is
      adequate in these patients. This study examined the quality of informed consent
      in hospitalized patients undergoing placement of gastrostomy tubes. METHODS:
      Retrospective review of the medical records of a cohort of 154 consecutive
      hospitalized adults undergoing placement of gastrostomy tubes in the context of
      chronic progressive illness, in the setting of a large community-teaching
      hospital. RESULTS: The medical record documented a procedure-specific discussion
      of benefits and burdens of and alternatives to tube feeding in only 1 of 154
      patients. Only 12 of 33 definitely or probably competent patients signed the
      hospital consent form; in the remaining 21, a surrogate decision-maker signed the
      form. The cumulative 1-year mortality for this cohort was 50%. CONCLUSIONS: The
      quality of informed consent for placement of gastrostomy tubes was inadequate in
      a large community-teaching hospital. Indirect evidence from the literature
      suggests that these results are not unique to this institution. Physicians should
      become more familiar with the medical and ethical issues relevant to medically
      administered nutrition near the end of life, and institutions should develop
      procedures to improve the quality of decision-making for patients considering
      this intervention.

PMID- 11231710
TI  - Cost-benefit analysis of a strategy to vaccinate healthy working adults against
      influenza.
AB  - BACKGROUND: Influenza is a major cause of illness, disruption to daily life, and
      work absenteeism among healthy working adults aged between 18 and 64 years. This
      group is not included among the traditional priority groups for annual
      vaccination. Immunization rates remain low. OBJECTIVE: To assess the economic
      implications of a strategy for annual vaccination of this group. METHODS: Using
      the societal perspective, this cost-benefit analysis included the direct and
      indirect costs associated with vaccination as well as the direct and indirect
      costs prevented by vaccination. Clinical and economic variable estimates were
      derived primarily from the published literature. For this model, it was assumed
      that vaccination occurred in efficient, low-cost settings such as at the work
      site. Monte Carlo simulation was used to calculate the mean net costs or savings
      along with the 95% probability interval, and sensitivity analyses explored the
      sensitivity of the cost model to different values of the input variables.
      RESULTS: Vaccinating healthy working adults was on average cost saving, with mean
      savings of $13.66 per person vaccinated (95% probability interval: net savings of
      $32.97 to net costs of $2.18), with vaccination generating net savings 95% of the
      time. The model was most sensitive to the influenza illness rate, the work
      absenteeism rate due to influenza, and hourly wages. In the worst-case scenario
      vaccination was not cost saving. Vaccination also generated net costs to society
      during years with a poor vaccine-circulating virus strain match. In all of the
      other sensitivity analysis scenarios, vaccination was cost saving. CONCLUSION:
      Influenza vaccination of healthy working adults on average is cost saving. These
      findings support a strategy of routine, annual vaccination for this group,
      especially when vaccination occurs in efficient and low-cost sites.

PMID- 11231712
TI  - Intranasal tranexamic acid treatment for severe epistaxis in hereditary
      hemorrhagic telangiectasia.

PMID- 11231711
TI  - Minimum instructional and program-specific administrative costs of educating
      residents in internal medicine.
AB  - BACKGROUND: The cost associated with education of residents is of interest from
      an educational as well as a political perspective. Most studies report a single
      institution's actual incurred costs, based on traditional cost accounting
      methods. We quantified the minimum instructional and program-specific
      administrative costs for residency training in internal medicine. METHODS: Using
      the Accreditation Council for Graduate Medical Education program requirements for
      internal medicine as minimum standards for teaching and administrative effort, we
      quantified the minimum instructional and administrative costs for sponsorship of
      an accredited residency program in internal medicine. We also analyzed the impact
      of resident complement and program curricular emphasis (outpatient, inpatient, or
      traditional) on the per-resident cost. The main outcome measure was the minimum
      annual per-resident cost of instruction and program-specific administration.
      RESULTS: Using the assumptions in this model, we estimated the annual cost per
      resident of implementing the program requirements to be $50,648, $35,477,
      $28,517, and $26,197 for inpatient intensive residency programs with resident
      complements of 21, 42, 84, and 126, respectively. For outpatient intensive
      residency programs of identical resident complements, we estimated the annual per
      resident cost to be $58,025, $42,853, $35,894, and $33,574 for similar resident
      complements. Fixed costs mandated by the program requirements, which did not vary
      across program size or configuration, were estimated to be $640,737. CONCLUSIONS:
      There are fixed and variable costs associated with sponsorship of accredited
      internal medicine residency programs. The minimum cost per resident of education
      and departmental administration varies inversely with program size within the
      sizes examined.

PMID- 11231713
TI  - Adult-onset type 1 diabetes with DIDMOAD syndrome-like manifestations.

PMID- 11231715
TI  - New treatment for harvest mite infestation.

PMID- 11231714
TI  - What do the people think (and know) about informed consent for participation in a
      medical trial.

PMID- 11231716
TI  - Psychosomatic heart disease.

PMID- 11231717
TI  - The primary deficiency resulting from acute severe illness in
      nonimmunocompromised patients is not the CD4+ subtype, but the total number of
      lymphocytes.

PMID- 11231718
TI  - Observational data do not establish cause and effect.

PMID- 11231719
TI  - Reduction of lipoprotein(a) in postmenopausal women.

PMID- 11231720
TI  - The role of HRT in cardiovascular disease.

PMID- 11231722
TI  - Multivitamin supplements are effective and inexpensive agents to lower
      homocysteine levels.

PMID- 11231724
TI  - Headache, hypertension, and irbesartan therapy.

PMID- 11231726
TI  - Dalteparin vs warfarin in hip arthroplasty patients.

PMID- 11231729
TI  - A piece of my mind. Moral wounds: complicated complications.

PMID- 11231730
TI  - Talking with Alan I. Leshner, PhD, National Institute on Drug Abuse Director.
      Interview by Brian Vastag.

PMID- 11231731
TI  - Immediate prescription coverage in doubt for Medicare recipients.

PMID- 11231732
TI  - Parents "letting rip" at British pediatricians.

PMID- 11231734
TI  - From the Food and Drug Administration.

PMID- 11231738
TI  - Do back belts prevent back injury?

PMID- 11231739
TI  - Do back belts prevent back injury?

PMID- 11231742
TI  - Loss and the duration of grief.

PMID- 11231743
TI  - Rapid loss of insulin secretion in a patient with fulminant type 1 diabetes
      mellitus and carbamazepine hypersensitivity syndrome.

PMID- 11231744
TI  - Abacavir-lamivudine-zidovudine vs indinavir-lamivudine-zidovudine in
      antiretroviral-naive HIV-infected adults: A randomized equivalence trial.
AB  - CONTEXT: Abacavir, a nucleoside analogue, has demonstrated suppression of human
      immunodeficiency virus (HIV) replication alone and in combination therapy.
      However, the role of abacavir in a triple nucleoside combination regimen has not
      been evaluated against a standard protease inhibitor-containing regimen for
      initial antiretroviral treatment. OBJECTIVE: To evaluate antiretroviral
      equivalence and safety of an abacavir-lamivudine-zidovudine regimen compared with
      an indinavir-lamivudine-zidovudine regimen. DESIGN AND SETTING: A multicenter,
      phase 3, randomized, double-blind trial with an enrollment period from August
      1997 to June 1998, with follow-up through 48 weeks at 73 clinical research units
      in the United States, Canada, Australia, and Europe. PATIENTS: Five hundred sixty
      two antiretroviral-naive, HIV-infected adults with a plasma HIV RNA level of at
      least 10 000 copies/mL and a CD4 cell count of at least 100 x 10(6)/L.
      INTERVENTIONS: Patients were stratified by baseline HIV RNA level and randomly
      assigned to receive a combination tablet containing 150 mg of lamivudine and 300
      mg of zidovudine twice daily plus either 300 mg of abacavir twice daily and
      indinavir placebo or 800 mg of indinavir every 8 hours daily plus abacavir
      placebo. After 16 weeks, patients with confirmed HIV RNA levels greater than 400
      copies/mL were eligible to continue receiving randomized treatment or receive
      open-label therapy. MAIN OUTCOME MEASURE: Virologic suppression, defined as HIV
      RNA concentration of 400 copies/mL or less at week 48. RESULTS: The proportion of
      patients who met the end point of having an HIV RNA level of 400 copies/mL or
      less at week 48 was equivalent in the abacavir group (51% [133/262]) and in the
      indinavir group (51% [136/265]) with a treatment difference of -0.6% (95%
      confidence interval [CI], -9% to 8%). In patients with baseline HIV RNA levels
      greater than 100 000 copies/mL, the proportion of patients achieving less than 50
      copies/mL was greater in the indinavir group than in the abacavir group with 45%
      (45/100) vs 31% (30/96) and a treatment diference of -14% (95% CI, -27% to 0%).
      The 2 treatments were comparable with respect to their effects on CD4 cell count.
      There was no difference between groups in the frequency of treatment-limiting
      adverse events or laboratory abnormalities. One death in the abacavir group was
      attributed to hypersensitivity reaction, which occurred following rechallenge
      with abacavir, approximately 3 weeks after initiating study treatment.
      CONCLUSIONS: In this study of antiretroviral-naive HIV-infected adults, the
      triple nucleoside regimen of abacavir-lamivudine-zidovudine was equivalent to the
      regimen of indinavir-lamivudine-zidovudine in achieving a plasma HIV RNA level of
      less than 400 copies/mL at 48 weeks.

PMID- 11231745
TI  - Relationship between trauma center volume and outcomes.
AB  - CONTEXT: The premise underlying regionalization of trauma care is that larger
      volumes of trauma patients cared for in fewer institutions will lead to improved
      outcomes. However, whether a relationship exists between institutional volume and
      trauma outcomes remains unknown. OBJECTIVE: To evaluate the association between
      trauma center volume and outcomes of trauma patients. DESIGN: Retrospective
      cohort study. SETTING: Thirty-one academic level I or level II trauma centers
      across the United States participating in the University Healthsystem Consortium
      Trauma Benchmarking Study. PATIENTS: Consecutive patients with penetrating
      abdominal injury (PAI; n = 478) discharged between November 1, 1997, and July 31,
      1998, or with multisystem blunt trauma (minimum of head injury and lower
      extremity long-bone fractures; n = 541) discharged between June 1 and December
      31, 1998. MAIN OUTCOME MEASURES: Inpatient mortality and hospital length of stay
      (LOS), comparing high-volume (>650 trauma admissions/y) and low-volume (</=650
      admissions/y) centers. RESULTS: After multivariate adjustment for patient
      characteristics and injury severity, the relative odds of death was 0.02 (95%
      confidence interval [CI], 0.002-0.25) for patients with PAI admitted with shock
      to high-volume centers compared with low-volume centers. No benefit was evident
      in patients without shock (P =.50). The adjusted odds of death in patients with
      multisystem blunt trauma who presented with coma to a high-volume center was 0.49
      (95% CI, 0.26-0.93) vs low-volume centers. No benefit was observed in patients
      without coma (P =.05). Additionally, a shorter LOS was observed in patients with
      PAI and New Injury Severity Scores of 16 or higher (difference in adjusted mean
      LOS, 1.6 days [95% CI, -1.5 to 4.7 days]) and in all patients with multisystem
      blunt trauma admitted to higher-volume centers (difference in adjusted mean LOS,
      3.3 days [95% CI, 0.91-5.70 days]). CONCLUSIONS: Our results indicate that a
      strong association exists between trauma center volume and outcomes, with
      significant improvements in mortality and LOS when volume exceeds 650 cases per
      year. These benefits are only evident in patients at high risk for adverse
      outcomes.

PMID- 11231746
TI  - Using Internet technology to deliver a behavioral weight loss program.
AB  - CONTEXT: Rapid increases in access to the Internet have made it a viable mode for
      public health intervention. No controlled studies have evaluated this resource
      for weight loss. OBJECTIVE: To determine whether a structured Internet behavioral
      weight loss program produces greater initial weight loss and changes in waist
      circumference than a weight loss education Web site. DESIGN: Randomized,
      controlled trial conducted from April to December 1999. SETTING AND PARTICIPANTS:
      Ninety-one healthy, overweight adult hospital employees aged 18 to 60 years with
      a body mass index of 25 to 36 kg/m(2). Analyses were performed for the 65 who had
      complete follow-up data. INTERVENTIONS: Participants were randomly assigned to a
      6-month weight loss program of either Internet education (education; n = 32 with
      complete data) or Internet behavior therapy (behavior therapy; n = 33 with
      complete data). All participants were given 1 face-to-face group weight loss
      session and access to a Web site with organized links to Internet weight loss
      resources. Participants in the behavior therapy group received additional
      behavioral procedures, including a sequence of 24 weekly behavioral lessons via e
      mail, weekly online submission of self-monitoring diaries with individualized
      therapist feedback via e-mail, and an online bulletin board. MAIN OUTCOME
      MEASURES: Body weight and waist circumference, measured at 0, 3, and 6 months,
      compared the 2 intervention groups. RESULTS: Repeated-measures analyses showed
      that the behavior therapy group lost more weight than the education group (P
      =.005). The behavior therapy group lost a mean (SD) of 4.0 (2.8) kg by 3 months
      and 4.1 (4.5) kg by 6 months. Weight loss in the education group was 1.7 (2.7) kg
      at 3 months and 1.6 (3.3) kg by 6 months. More participants in the behavior
      therapy than education group achieved the 5% weight loss goal (45% vs 22%; P
      =.05) by 6 months. Changes in waist circumference were also greater in the
      behavior therapy group than in the education group at both 3 months (P =.001) and
      6 months (P =.005). CONCLUSIONS: Participants who were given a structured
      behavioral treatment program with weekly contact and individualized feedback had
      better weight loss compared with those given links to educational Web sites.
      Thus, the Internet and e-mail appear to be viable methods for delivery of
      structured behavioral weight loss programs.

PMID- 11231747
TI  - Effects of vitamin E on lipid peroxidation in healthy persons.
AB  - CONTEXT: Oxidative stress may play a role in the development or exacerbation of
      many common diseases. However, results of prospective controlled trials of the
      effects of antioxidants such as vitamin E are contradictory. OBJECTIVE: To assess
      the effects of supplemental vitamin E on lipid peroxidation in vivo in healthy
      adults. DESIGN: Randomized, double-blind, placebo-controlled trial conducted
      March 1999 to June 2000. SETTING: A general clinical research center in a
      tertiary referral academic medical center. PARTICIPANTS: Thirty healthy men and
      women aged 18 to 60 years. INTERVENTIONS: Participants were randomly assigned to
      receive placebo or alpha-tocopherol dosages of 200, 400, 800, 1200, or 2000 IU/d
      for 8 weeks (n = 5 in each group), followed by an 8-week washout period. MAIN
      OUTCOME MEASURES: Three indices of lipid peroxidation, urinary 4-hydroxynonenal
      (4-HNE) and 2 isoprostanes, iPF(2alpha)-III and iPF(2alpha)-VI, measured by gas
      chromatography/mass spectrometry and compared among the 6 groups at baseline, 2,
      4, 6, and 8 weeks, and 1, 3, and 8 weeks after discontinuation. RESULTS:
      Circulating vitamin E levels increased in a dose-dependent manner during the
      study. No significant effect of vitamin E on levels of urinary 4-HNE or either
      isoprostane was observed. Mean (SEM) baseline vs week 8 levels of iPF(2alpha)-III
      were 154 (20.1) vs 168 (22.3) pg/mg of creatinine for subjects taking placebo;
      165 (19.6) vs 234 (30.1) pg/mg for those taking 200 IU/d of vitamin E; and 195
      (26.7) vs 213 (40.6) pg/mg for subjects taking 2000 IU/d. Corresponding
      iPF(2alpha)-VI levels were 1.43 (0.6) vs 1.62 (0.4) ng/mg of creatinine for
      subjects taking placebo; 1.64 (0.3) vs 1.24 (0.8) ng/mg for those taking 200 IU/d
      of vitamin E; and 1.83 (0.3) vs 1.94 (0.9) ng/mg for those taking 2000 IU/d.
      Baseline vs week 8 levels of 4-HNE were 0.5 (0.04) vs 0.4 (0.05) ng/mg of
      creatinine for subjects taking placebo; 0.4 (0.06) vs 0.5 (0.02) ng/mg with 200
      IU/d of vitamin E; and 0.2 (0.02) vs 0.2 (0.1) ng/mg with 2000 IU/d. CONCLUSIONS:
      Our results question the rationale for vitamin E supplementation in healthy
      individuals. Specific quantitative indices of oxidative stress in vivo should be
      considered as entry criteria and for dose selection in clinical trials of
      antioxidant drugs and vitamins in human disease.

PMID- 11231748
TI  - Time trends in autism and in MMR immunization coverage in California.
AB  - CONTEXT: Considerable concern has been generated in the lay and medical
      communities by a theory that increased measles-mumps-rubella (MMR) immunization
      among young children may be the cause of an apparent marked increase in autism
      occurrence. OBJECTIVE: To determine if a correlation exists in secular trends of
      MMR immunization coverage among young children and autism occurrence. DESIGN,
      SETTING, AND PARTICIPANTS: Retrospective analyses of MMR immunization coverage
      rates among children born in 1980-1994 who were enrolled in California
      kindergartens (survey samples of 600-1900 children each year) and whose school
      immunization records were reviewed to retrospectively determine the age at which
      they first received MMR immunization; and of autism caseloads among children born
      in these years who were diagnosed with autism and were enrolled in the California
      Department of Developmental Services regional service center system. MAIN OUTCOME
      MEASURES: Measles-mumps-rubella immunization coverage rates as of ages 17 months
      and 24 months and numbers of Department of Developmental Services system
      enrollees diagnosed with autism, grouped by year of birth. RESULTS: Essentially
      no correlation was observed between the secular trend of early childhood MMR
      immunization rates in California and the secular trend in numbers of children
      with autism enrolled in California's regional service center system. For the 1980
      1994 birth cohorts, a marked, sustained increase in autism case numbers was
      noted, from 44 cases per 100 000 live births in the 1980 cohort to 208 cases per
      100 000 live births in the 1994 cohort (a 373% relative increase), but changes in
      early childhood MMR immunization coverage over the same time period were much
      smaller and of shorter duration. Immunization coverage by the age of 24 months
      increased from 72% to 82%, a relative increase of only 14%, over the same time
      period. CONCLUSIONS: These data do not suggest an association between MMR
      immunization among young children and an increase in autism occurrence.

PMID- 11231749
TI  - HIV infection in women in the United States: status at the Millennium.
AB  - CONTEXT: During the past decade, knowledge of human immunodeficiency virus (HIV)
      infection in women has expanded considerably but may not be easily accessible for
      use in understanding and prioritizing the clinical needs of HIV-infected women.
      OBJECTIVES: To perform a comprehensive review of epidemiologic, clinical,
      psychosocial, and behavioral information about HIV in women, and to recommend an
      agenda for future activities. DATA SOURCES: A computerized search, using MEDLINE
      and AIDSline, of published literature was conducted; journal articles from
      January 1981 through July 2000 and scientific conference presentations from
      January 1999 through July 2000 were retrieved and reviewed for content; article
      reference lists were used to identify additional articles and presentations of
      interest. STUDY SELECTION: Data from surveillance and prospective cohort studies
      with at least 20 HIV-infected women and appropriate comparison groups were
      preferentially included. DATA EXTRACTION: Included studies of historical
      importance and subsequent refined analyses of topics covered therein; these and
      studies with more current data were given preference. Four studies involving
      fewer than 20 women were included; 2 studies were of men only. DATA SYNTHESIS:
      Women account for an increasing percentage of all acquired immunodeficiency
      syndrome (AIDS) cases, from 6.7% (1819/27 140 cases) in 1986 to 18% (119 810/724
      656 cases) in 1999. By the end of 1998, of all newly reported AIDS cases among
      women, proportionally more were in the South (41%), among black women (61%), and
      from heterosexual transmission (38%). Of note, increasingly more women have no
      identified or reported risk, about half or more of whom are estimated to be
      infected heterosexually. It is estimated that a total of at least 54% of women
      newly reported with AIDS in 1998 acquired HIV through heterosexual sex, including
      women in the no identified or reported risk category estimated to have been
      infected heterosexually, meeting the surveillance heterosexual risk definition.
      Natural history, progression, survival, and HIV-associated illnesses-except for
      those of the reproductive tract-thus far appear to be similar in HIV-infected
      women and men. Although antiretroviral therapy has proven to be highly effective
      in improving HIV-related morbidity and mortality rates, women may be less likely
      than men to use these therapies. Drug use, high-risk sex behaviors, depression,
      and unmet social needs interfere with women's use of available HIV prevention and
      treatment resources. CONCLUSIONS: Continued research on HIV pathogenesis and
      treatment is needed; however, emphasis should also be placed on using existing
      knowledge to improve the clinical care of women by enhancing use of available
      services and including greater use of antiretroviral therapy options, treating
      depression and drug use, facilitating educational efforts, and providing social
      support for HIV-infected women.

PMID- 11231750
TI  - Improving survival from sudden cardiac arrest: the role of the automated external
      defibrillator.
AB  - CONTEXT: Sudden cardiac death is a major public health problem in the United
      States, and improving survival after out-of-hospital cardiac arrest has been the
      subject of intense study. Early defibrillation has been shown to be critical to
      improving survival. Use of automated external defibrillators (AEDs) has become an
      important component of emergency medical systems, and recent advances in AED
      technology have allowed expansion of AED use to nontraditional first responders
      and the lay public. OBJECTIVES: To examine advancements in AED technology, review
      the impact of AEDs on time to defibrillation and survival, and explore the future
      role of AEDs in the effort to improve survival following sudden cardiac arrest.
      DATA SOURCES: MEDLINE was searched for articles from 1966 through December 2000
      (Medical Subject Headings: electric countershock, heart arrest, resuscitation,
      emergency medical services; keywords: automatic external defibrillator, automated
      external defibrillator, public access defibrillation). Reference lists of
      relevant articles, news releases, and product information from manufacturers were
      also reviewed. STUDY SELECTION: Initial MEDLINE search produced 4816 articles,
      from which 101 articles were selected for referencing based on having been
      published in a peer-reviewed journal and on relevance to the subject of the
      manuscript as determined by all 5 authors. DATA EXTRACTION: All studies were
      critically reviewed for relevance, accuracy, and quality of data and study design
      by all authors. DATA SYNTHESIS: Recent advances in AED technology and design have
      resulted in marked simplification of AED operation, improvements in accuracy and
      effectiveness, and reductions in cost. Use of AEDs by first responders and
      laypersons has reduced time to defibrillation and improved survival from sudden
      cardiac arrest in several communities. Initial studies of the cost-effectiveness
      of AED use in comparison with other commonly used treatments are favorable.
      CONCLUSION: The AED represents an efficient method of delivering defibrillation
      to persons experiencing out-of-hospital cardiac arrest and its use by both
      traditional and nontraditional first responders appears to be safe and effective.
      The rapidly expanding role of AEDs in traditional emergency medical systems is
      supported by the literature, and initial studies of public access to
      defibrillation offer hope that further improvements in survival after sudden
      cardiac death can be achieved.

PMID- 11231751
TI  - Monitoring and ensuring safety during clinical research.
AB  - Increased numbers of clinical trials, many of which are large, multicenter, and
      sometimes international, and the marked shift of funding for clinical trials to
      industry have made apparent the inadequacy of mechanisms for protecting human
      subjects that were developed when clinical research was generally carried out on
      a small scale at single institutions. To address concerns regarding the
      protection of human subjects, a group of professionals with expertise in various
      aspects of clinical trials was assembled in May 2000. Participants described and
      evaluated the mechanisms by which clinical trials are monitored, focusing on
      adverse event reporting and the processes by which various parties with oversight
      responsibilities interact in the course of these trials. In this article, we
      describe the manner in which adverse event reporting might function to enhance
      safety and the role of data monitoring committees in using aggregate data from
      these reports, outline the problems that now exist for institutional review
      boards as they are faced with multiple adverse event reports from clinical trials
      while conducting continuing review, and offer recommendations for improving the
      current approach.

PMID- 11231752
TI  - Scientific and ethical issues in equivalence trials.

PMID- 11231754
TI  - msJAMA: new approaches to health care for displaced populations.

PMID- 11231755
TI  - msJAMA: assessment of trauma in primary care.

PMID- 11231757
TI  - msJAMA: human rights violations and refugee health.

PMID- 11231756
TI  - msJAMA: from war zone to contact zone: culture and refugee mental health
      services.

PMID- 11231758
TI  - msJAMA: interview with Philip Gourevitch: international responses to genocide in
      Rwanda. Interview by Gina Jae.

PMID- 11231759
TI  - msJAMA: mental health challenges in postwar Kosova.

PMID- 11231765
TI  - Increased corneal thickness in patients with ocular hypertension.
AB  - BACKGROUND: Central corneal thickness greater than 0.520 mm causes true
      intraocular pressure to be overestimated when the technique of applanation
      tonometry is used to measure intraocular pressure. OBJECTIVE: To compare the
      corneal thickness measurements of patients enrolled in a study of ocular
      hypertension with those of age-matched control subjects with normal intraocular
      pressure. METHODS: Central corneal pachymetry using an optical pachymeter was
      performed on each study subject (n = 55) at baseline and in an independent sample
      of control subjects. A 2 sample, 2-tailed T test was used to compare the 2
      populations. RESULTS: The patients with ocular hypertension had significantly
      higher mean corneal thickness measurements (mean +/- SD, 0.594 +/- 0.037 mm) than
      the control group (0.563 +/- 0.027 mm) (P<.001). CONCLUSION: Corneal thickness
      may be a confounding factor in the measurement of intraocular pressure, and this
      may modify the risk for progression to glaucoma in patients with ocular
      hypertension.

PMID- 11231766
TI  - Tear tryptase in vernal keratoconjunctivitis.
AB  - OBJECTIVES: To determine the tear level of tryptase (a marker of mast cell
      activation) in vernal keratoconjunctivitis (VKC) before and after treatment. In
      addition, eosinophil counts in conjunctival scrapings and ocular surface
      temperature before and after treatment were studied. PATIENTS AND METHODS: A
      total of 20 patients, 7 years or older with VKC, were included in this study.
      Tear samples for tryptase determination were collected before and 2 weeks after
      treatment with 4% disodium cromoglycate eyedrops and 0.1% fluorometholone
      eyedrops. In addition, conjunctival scrapings were obtained for microscopic
      evaluation, and measurement of the ocular surface temperature was performed
      before and 2 weeks after treatment. One patient was excluded because the patient
      did not receive topical treatment. Control tear samples were collected from 20
      normal control patients for tryptase determination. RESULTS: There were 19
      patients with VKC (17 males, 2 females). The age range was 7 to 17 years with a
      mean age of 9 years. The mean number of eosinophils prior to initiation of
      therapy was 11.37 eosinophils with a range of 1 to 34 per high-power field.
      Following treatment, the mean number of eosinophils was 3.42 eosinophils per high
      power field with a range of 0 to 11 (P<.01). The mean ocular surface temperature
      for the right eye before treatment was 35.56 degrees C (range, 34.46 degrees C
      36.50 degrees C) and after treatment was 33.53 degrees C (range, 31.13 degrees C
      35.40 degrees C). For the left eye, the mean ocular surface temperature before
      treatment was 35.49 degrees C (range, 34.86 degrees C-36.16 degrees C) and after
      treatment was 33.88 degrees C (range, 32.40 degrees C-35.53 degrees C). The
      ocular surface temperature was found to decrease significantly following
      treatment (P<.001). The levels of tryptase in tears of patients with VKC were
      determined before and after treatment. The mean level was 16.77 ng/mL (range, <5
      115 ng/mL). Following treatment with topical 4% disodium cromoglycate and 0.1%
      fluorometholone eyedrops, the mean level of tryptase decreased to 7.29 ng/mL
      (range, <5-44.1 ng/mL) (P<.05). CONCLUSIONS: Patients with severe VKC had high
      levels of tryptase in tears. Following treatment, the level of tryptase in tears
      decreased significantly.

PMID- 11231767
TI  - Diode laser transscleral cyclophotocoagulation as a primary surgical treatment
      for primary open-angle glaucoma.
AB  - OBJECTIVES: To evaluate the feasibility of diode laser transscleral
      cyclophotocoagulation (TSCPC) as a primary surgical treatment for primary open
      angle glaucoma and to compare 2 laser energy settings used for treatment.
      METHODS: In a prospective clinical trial in Cape Coast and Accra, Ghana, 1 eye of
      each of 92 patients with primary open-angle glaucoma was treated by diode laser
      TSCPC as a primary surgical treatment. Eyes were randomly assigned to receive
      treatment by 20 applications of either 1.5 W applied for 1.5 seconds or 1.25 W
      applied for 2.5 seconds. RESULTS: Seventy-nine (86%) of 92 patients completed 3
      months of follow-up; follow-up was 13.2 +/- 6.0 months (mean +/- SD). Intraocular
      pressure decreased in 53 (67%) of the 79 eyes. The drop in intraocular pressure
      was 20% or more in 37 eyes (47%) and final intraocular pressure was 22 mm Hg or
      less in 38 eyes (48%). An atonic pupil was a previously unreported complication
      that arose in 27 (28%) of 92 eyes. There were no serious complications of
      hypotony, phthisis bulbi, or sympathetic ophthalmia. Visual acuity decreased in
      18 (23%) of 79 eyes treated by TSCPC and in 10 (23%) of 47 fellow eyes treated
      only with glaucoma medications. There was no difference in outcomes between the 2
      laser energy settings. CONCLUSIONS: Diode laser TSCPC is a practical, rapid, well
      tolerated procedure that may provide a modest and variable lowering of
      intraocular pressure. The treatment, used with conservative energy levels applied
      to the eye, seems to have few serious complications, although a previously
      unrecognized complication of atonic pupil needs further evaluation. A moderate
      variation in laser energy settings does not influence the results of treatment.

PMID- 11231768
TI  - Safety of indocyanine green angiography during pregnancy: a survey of the retina,
      macula, and vitreous societies.
AB  - OBJECTIVES: To establish current practice patterns and assess the general
      knowledge among vitreoretinal-trained physicians regarding the use of indocyanine
      green (ICG) angiography during pregnancy, and to review the literature regarding
      the established safety of ICG angiography in pregnant women. METHODS: A survey
      was mailed to 1101 members of the Retina, Macula, and Vitreous Societies.
      RESULTS: Of the 520 respondents, 434 (83%) had seen at least 1 pregnant woman who
      required ICG angiography or fluorescein angiography. Of these, 385 (89%) withheld
      fluorescein angiography and 105 (24%) withheld ICG angiography, largely because
      of fear of teratogenicity or lawsuit. Diabetic retinopathy and choroidal
      neovascular membrane were the most common indications for fluorescein
      angiography, and choroidal neovascular membrane and choroidal tumor were the most
      common indications for ICG angiography. Only 24% thought that it was safe to use
      ICG angiography in a pregnant patient, and only 5% thought it was safer than
      fluorescein angiography. CONCLUSIONS: Despite the documented safety of ICG when
      used for retinal angiography and the extensive experience with the use of
      intravenous ICG to measure hepatic blood flow in pregnant women, the results of
      this survey suggest widespread hesitation to use ICG for retinal angiography in
      pregnant women. Current practice patterns regarding the use of ICG angiography in
      pregnant patients may be unnecessarily restrictive.

PMID- 11231769
TI  - Phenotypic subtypes of Stargardt macular dystrophy-fundus flavimaculatus.
AB  - OBJECTIVE: To determine if phenotypic subtypes exist in Stargardt macular
      dystrophy-fundus flavimaculatus (SMD-FFM). METHODS: A cross-sectional study of 63
      patients with autosomal recessive SMD-FFM was undertaken. The age of onset,
      duration of symptoms, visual acuity, and clinical features on fundus examination,
      color fundus photographs, and fundus autofluorescence images were recorded.
      Electrophysiological tests, including pattern, focal, and full-field
      electroretinogram (ERG), electro-oculogram, and color-contrast sensitivity
      measurement, were also performed. RESULTS: Based on electrophysiological
      attributes (ERG), patients with SMD-FFM could be classified into 3 groups. In
      group 1, there was severe pattern ERG abnormality with normal scotopic and full
      field ERGs. In group 2, there was additional loss of photopic function, and in
      group 3, there was loss of both photopic and scotopic function. Differences in
      scotopic or photopic function among groups were not explained on the basis of
      differences in age of onset or duration of disease. CONCLUSIONS: Patients with
      SMD-FFM can be classified into 3 groups based on the absence or presence of
      generalized loss of either photopic or photopic and scotopic function. It appears
      that these 3 groups may represent distinct phenotypic subtypes in SMD-FFM.

PMID- 11231770
TI  - Overexpression of epidermal growth factor receptor restricted to macrophages in
      uveal melanoma.
AB  - OBJECTIVE: To determine whether expression of the epidermal growth factor
      receptor (EGFR) is of prognostic value in uveal melanoma. METHODS: Thirty
      consecutive patients treated for primary posterior uveal melanoma by enucleation
      or local resection were studied. Tumors were examined for EGFR and CD68
      expression by immunohistochemistry on formalin-fixed, paraffin-embedded sections.
      Extracted DNA from paired frozen tumor and blood samples was examined for loss of
      heterozygosity on chromosome 3 using polymerase chain reaction-based
      microsatellite analysis. Immunoreactivity for EGFR was correlated with
      clinicopathological, chromosome 3, and follow-up data. RESULTS: Immunoreactivity
      for EGFR was observed in 7 (23%) of 30 uveal melanomas, but was restricted to
      solitary or small groups of cells with macrophage-like morphology. Immunoreactive
      cells were confirmed as macrophages using an antibody to the macrophage marker
      CD68. Chromosome 3 loss, epithelioid cells, and microvascular loops were detected
      in 17 (57%), 22 (73%) and 19 (63%) of the 30 tumors, respectively. Metastatic
      disease was detected in 5 patients (17%). No correlation was found between any of
      these variables and EGFR positivity. CONCLUSIONS: The absence of EGFR
      immunoreactivity in tumor cells does not support the use of EGFR expression as a
      prognostic indicator in patients with uveal melanoma. Future EGFR studies in
      uveal melanoma should be interpreted with caution in view of our findings that
      tumor-associated macrophages can express this receptor.

PMID- 11231771
TI  - Pediatric enucleation: analysis of volume replacement.
AB  - OBJECTIVES: To determine the percent volume replacement by an implant and
      prosthesis, the long-term sequelae of poor volume replacement, and specific
      guidelines for volume replacement in pediatric patients. METHODS: A retrospective
      observational study of 16 pediatric patients who underwent enucleation (group 1)
      and 31 adult patients enucleated in childhood (group 2) was performed. The total
      volume replacement and the volume replacement by the implant were determined. The
      incidence of secondary surgical procedures for superior sulcus deformity,
      enophthalmos, ptosis, ectropion, and socket contraction was determined. RESULTS:
      The average percent volume replaced by the implants in group 1 patients was 68%.
      The average percent volume replaced by the implants in group 2 patients was 21%.
      Seventy-one percent of patients in group 2 underwent secondary implant surgery to
      augment volume and eliminate superior sulcus deformity and enophthalmos.
      CONCLUSIONS: The placement of an adequately sized implant in pediatric patients
      may obviate the need for secondary augmentation of socket volume in adulthood.
      The authors suggest an implant 2 mm less in diameter than the axial length of the
      eye in pediatric patients.

PMID- 11231772
TI  - Enhanced disruption of the blood-aqueous barrier and the incidence of
      angiographic cystoid macular edema by topical timolol and its preservative in
      early postoperative pseudophakia.
AB  - OBJECTIVE: To investigate the effects of timolol maleate with preservative and
      its preserved (PV) and nonpreserved vehicles (NPV) (benzalkonium chloride) on the
      blood-aqueous barrier and angiographic cystoid macular edema (CME) in early
      postoperative pseudophakia. PATIENTS AND METHODS: Patients with ocular
      hypertension, normal tension glaucoma, and primary open-angle glaucoma who
      underwent surgery for cataracts. The study included a double-masked trial for
      timolol, PV, and NPV and a single-masked trial on the effect of diclofenac sodium
      and fluorometholone acetate on all three. The patients were divided into 6
      groups, each of which were simultaneously administered the following different
      combinations of compounds: timolol and diclofenac (group A), timolol and
      fluorometholone (group B), PV and diclofenac (group C), PV and fluorometholone
      (group D), NPV and diclofenac (group E), and NPV and fluorometholone (group F).
      The 6 groups were then compared using a laser flare cell meter to determine the
      degree of disruption of the blood-aqueous barrier and fluorescein angiography to
      investigate angiographic CME. The differences in mean daily fluctuations in
      intraocular pressure were compared on the preoperative baseline day and for 5
      weeks postoperatively. Twice daily administration of 0.5% timolol maleate or the
      vehicles was started 2 days before surgery, and continued until 5 weeks after
      surgery. Diclofenac or fluorometholone drops were instilled in the eyes 4 times
      preoperatively, on the day of surgery, and 3 times daily for 5 weeks
      postoperatively. RESULTS: The flare amount was higher on the third and seventh
      days in group B than in group D, but was the same after the seventh day. The
      incidence of angiographic CME was the same between both groups. These 2 factors
      were significantly lower in group F. These 2 factors were also significantly
      lower in the 3 groups that received diclofenac instead of fluorometholone, with
      no difference among these groups. The intraocular pressure decline was
      significant in groups that received timolol compared with groups that received PV
      or NPV. CONCLUSIONS: Timolol and its preservative, benzalkonium chloride, cause
      disruption of the blood-aqueous barrier in early postoperative pseudophakia and
      increased incidence of angiographic CME. The concurrent administration of
      nonsteroidal anti-inflammatory drug such as diclofenac prevents these adverse
      effects without interfering with the drop in intraocular pressure caused by
      timolol. The addition of benzalkonium chloride to timolol contributes
      considerably to these adverse effects. CLINICAL RELEVANCE: The present results
      suggest the cause of similar complications produced by other antiglaucoma
      eyedrops containing similar preservatives.

PMID- 11231773
TI  - Intravitreal triamcinolone acetonide inhibits choroidal neovascularization in a
      laser-treated rat model.
AB  - OBJECTIVE: To determine if intravitreal triamcinolone acetonide (TAAC) inhibits
      experimental choroidal neovascular membranes induced by laser trauma in a rat
      model. METHODS: Nineteen anesthetized male Brown Norway rats received a series of
      8 krypton red laser lesions per eye (647 nm, 0.05 seconds, 50 microm, and 150 mW
      in 17 rats, and 200 mW in 2 rats). One eye received an intravitreal injection of
      triamcinolone acetonide (20 microL, 0.8 mg) and the other eye received an
      injection of isotonic sodium chloride solution. Fundus and fluorescein
      angiography examinations occurred just before euthanasia and tissue processing
      for histopathology on day(s) 0, 1, 3, 7, 14, 21, 28, and 35. RESULTS: From the
      control eyes that underwent photocoagulation at 150 mW, 57 discrete lesions with
      definitive fibrovascular proliferations were observed at 21, 28, and 35 days,
      arising from a total of 72 spots placed (79% yield). From the control eyes that
      underwent photocoagulation at 200 mW, 11 discrete lesions with definitive
      fibrovascular proliferations were observed at 28 days, arising from a total of 16
      spots placed (69% yield). In the TAAC-treated group, no fibrovascular
      proliferations were observed in the 72 lesions and in the 16 lesions created with
      150 mW and 200 mW, respectively. CONCLUSION: Intravitreal TAAC is a potent
      inhibitor of fibrovascular proliferations in a rat model of choroidal neovascular
      membranes induced by laser trauma. CLINICAL RELEVANCE: This study corroborates
      previous investigations that propose TAAC as a potential treatment for choroidal
      neovascular membranes in humans.

PMID- 11231774
TI  - Aspirin use and risk of cataract in posttrial follow-up of Physicians' Health
      Study I.
AB  - BACKGROUND: In Physicians' Health Study I, randomized trial results indicated no
      major beneficial effect of 5 years of low-dose aspirin treatment on total
      cataract (relative risk [RR], 0.94; 95% confidence interval [CI], 0.79-1.13) or
      cataract extraction (RR, 0.81; 95% CI, 0.65-1.01) during the period of treatment.
      OBJECTIVE: To examine the effect of assigned aspirin treatment and posttrial,
      self-selected aspirin use on the risk of age-related cataract over the 15 years
      of follow-up of Physicians' Health Study I. METHODS: Participants were 20 968 US
      male physicians enrolled in Physicians' Health Study I who did not report
      cataract at baseline. At 7 years, after termination of the randomized aspirin
      component of the trial, self-selected aspirin use was computed from annual
      questionnaires. The main outcome measures were age-related cataract and
      extraction of age-related cataract, defined as an incident, age-related lens
      opacity responsible for a reduction in best-corrected visual acuity to 20/30 or
      worse based on self-report confirmed by medical record review. RESULTS: During a
      median of 14.9 years of follow-up, there were 2081 cataracts and 1198 cataract
      extractions. Overall, the age- and beta carotene-adjusted RR of cataract in men
      assigned to aspirin compared with those assigned to placebo was 1.09 (95% CI,
      1.00-1.18). For cataract extraction, the RR was 1.09 (95% CI, 0.98-1.22). During
      a median posttrial follow-up of 7.9 years, a total of 1225 incident cataracts and
      635 cataract extractions were documented. The multivariate RR of cataract in men
      who reported using aspirin frequently (>/=180 days per year) at 7 years compared
      with nonusers (0-13 days per year) was 1.20 (95% CI, 1.03-1.40). For cataract
      extraction, the multivariate RR was 1.22 (95% CI, 0.98-1.51). Results for
      diagnosis and extraction of cataract subtypes were similar. CONCLUSIONS: Analyses
      based on randomized aspirin assignment indicated no long-term benefit of 5 years
      of low-dose aspirin treatment on total cataract or cataract extraction.
      Posttrial, observational data also indicated no decreased risk of cataract in
      aspirin users and suggested a small increased risk of cataract in aspirin users.
      Further randomized trial data to investigate the effect of longer term treatment
      with low-dose aspirin are being collected as part of the ongoing Women's Health
      Study, a randomized trial of low-dose aspirin and vitamin E among 39 876
      apparently healthy, postmenopausal US female health professionals.

PMID- 11231775
TI  - Mutations in the CRB1 gene cause Leber congenital amaurosis.
AB  - OBJECTIVES: To test the hypothesis that mutations in the CRB1 gene cause Leber
      congenital amaurosis (LCA) and, if so, to describe the ocular phenotype of
      patients with LCA who harbor CRB1 sequence variations. PATIENTS: One hundred
      ninety probands with a clinical diagnosis of LCA were selected from a cohort of
      233 probands ascertained in 5 different countries. The remaining 43 probands
      (18%) were excluded because they harbored sequence variations in previously
      identified LCA genes. METHODS: One hundred ninety unrelated individuals with LCA
      were screened for coding sequence mutations in the CRB1 gene with single-strand
      conformation polymorphism analysis followed by automated DNA sequencing. RESULTS:
      Twenty-one of the 190 probands (9% of the total cohort of 233) and 2 (1.4%) of
      140 controls harbored amino acid-altering sequence variations in the CRB1 gene (P
      =.003). CONCLUSIONS: In our cohort of patients with LCA, coding sequence
      variations were observed in the CRB1 gene more frequently than in any of the
      other 5 known LCA-associated genes. Likely disease-causing sequence variations
      have now been identified in 64 (28%) of 233 subjects in this cohort. CLINICAL
      RELEVANCE: Molecular diagnosis can confirm and clarify the diagnosis in an
      increasing fraction of patients with LCA. As genotype data accumulate, clinical
      phenotypes associated with specific mutations may be established. This will
      facilitate the counseling of patients regarding their visual prognosis and the
      likelihood of associated systemic anomalies.

PMID- 11231776
TI  - A new role for diode laser transscleral cyclophotocoagulation?

PMID- 11231777
TI  - Implications of genetic analysis in Leber congenital amaurosis.

PMID- 11231778
TI  - Reflections on sex-related risk of eye disease.

PMID- 11231779
TI  - Progress in American ophthalmology from 1850 to 2000, as seen through the eyes of
      Frederick H. Verhoeff.

PMID- 11231780
TI  - Motility disturbance due to true Tenon cyst in a child with a Baerveldt glaucoma
      drainage implant.
AB  - Epithelial ingrowth of the bleb cavity, a true Tenon cyst, is a rare complication
      of a glaucoma drainage implant. Previous cases have been associated with
      persistent bleb leak, and most have occurred in eyes with prior extraocular
      surgery. We describe a case of a true Tenon cyst causing strabismus and an
      elevated intraocular pressure that was successfully treated by surgical revision.

PMID- 11231781
TI  - Orbital mass secondary to precursor T-cell acute lymphoblastic leukemia: a rare
      presentation.
AB  - We describe a 40-year-old woman with a history of precursor T-cell acute
      lymphoblastic leukemia who developed an orbital mass associated with diffuse
      infiltration of the paranasal sinuses. The clinical and radiologic findings
      suggested an orbital abscess. Examination of orbital and ethmoid sinus biopsy
      specimens revealed relapse of precursor T-cell acute lymphoblastic leukemia.
      Although orbital involvement by granulocytic sarcoma (also known as
      extramedullary myeloid cell tumor and chloroma) with or without concurrent acute
      myeloid leukemia is well described in the literature, similar presence of acute
      lymphoblastic leukemia of either precursor T-cell or B-cell lineage is rare.

PMID- 11231782
TI  - Case reports and small case series: late dislocation of a LASIK flap caused by a
      fingernail.

PMID- 11231783
TI  - Presumed bilateral medulloepithelioma.

PMID- 11231784
TI  - Routine neuroimaging in retinoblastoma for the detection of intracranial tumors.

PMID- 11231785
TI  - Ocular management of harlequin syndrome.

PMID- 11231786
TI  - Reliability and validity of a proposed dry eye evaluation scheme.

PMID- 11231788
TI  - Intravitreal injection of tissue plasminogen activator: four considerations.

PMID- 11231790
TI  - Additional considerations in cases involving persistent hyperplastic primary
      vitreous.

PMID- 11231792
TI  - Retinal toxic effects associated with intravitreal fomivirsen.

PMID- 11231793
TI  - Fresnel prism update.

PMID- 11231794
TI  - Reactive pericytes vs myofibroblastic tumor cells.

PMID- 11231796
TI  - Reducing gun carrying by youth.

PMID- 11231797
TI  - Complexities in recognizing and treating iron deficiency anemia.

PMID- 11231798
TI  - Factors preventing gun acquisition and carrying among incarcerated adolescent
      males.
AB  - CONTEXT: Despite the wide availability of guns in the United States, not all
      delinquent adolescents own guns and not all adolescent gun owners carry them at
      all times. Research about the factors that prevent high-risk youth from acquiring
      and carrying guns is limited. OBJECTIVE: To determine, from the perspective of
      incarcerated adolescent males, factors that prevent acquiring or carrying guns,
      either on a temporary or permanent basis. DESIGN AND SETTING: In-depth,
      semistructured interviews were conducted with randomly selected incarcerated
      adolescent males at a residential juvenile justice facility from January to May
      1998. Transcribed interviews were examined for recurrent themes. PARTICIPANTS:
      Forty-five incarcerated adolescent males. MAIN OUTCOME MEASURES: Reported factors
      limiting gun acquisition and carrying. RESULTS: Seventy-one percent of the sample
      had either owned or carried a gun out of their home. We identified 6 recurring
      themes that, at least on occasion, prevented or delayed delinquent youth from
      acquiring or carrying guns. The most commonly cited factors were fear of being
      arrested and incarcerated and lack of perceived need for a gun. Other themes
      included not wanting to hurt oneself or others, respect for the opinions of
      others, inability to find a source for a desired gun, and lack of money to
      acquire a desired gun. CONCLUSIONS: We identified 6 factors that limited gun
      acquisition and carrying among a sample of incarcerated male adolescents.
      Knowledge of these factors should inform intervention efforts to reduce youth gun
      acquisition and carrying.

PMID- 11231799
TI  - Witnessing violence among inner-city children of substance-abusing and non
      substance-abusing women.
AB  - OBJECTIVES: To determine if children of substance-abusing mothers witness more
      violence than children of non-substance-abusing (control) mothers, and to
      determine if children who witness violence have more behavioral problems and
      higher stress scores than children who do not witness violence. DESIGN: Cross
      sectional research design comparing exposure to violence among children of
      substance-abusing mothers and control mothers of low socioeconomic status.
      SETTING: An inner-city pediatric clinic. PARTICIPANTS: Forty substance-abusing
      mothers and their children, and 40 non-substance-abusing mothers and their
      children, examined when the children were 6 years old. MAIN OUTCOME MEASURES:
      Maternal report of children's exposure to violence was assessed using the
      Exposure to Violence Interview and the Conflict Tactics Scale. Maternal report of
      children's behavior was assessed using the Child Behavior Checklist and the
      Children's Response to Stress Inventory. RESULTS: Children of substance-abusing
      mothers did not witness more violence than the control children (P>.05). However,
      6-year-old inner-city children in the present study witnessed a high rate of
      violence: 43% had seen someone beaten up, 13% had seen someone threatened with a
      knife, and 7% had seen someone stabbed or shot. Children witnessing violence had
      significantly higher aggressive, delinquent, anxious/depressed, withdrawn,
      attention, and social problems (P<.05) on the Child Behavior Checklist, and
      higher stress scores (P =.05) on the Children's Response to Stress Inventory.
      CONCLUSIONS: More than half of the 6-year-old inner-city children in the present
      study witnessed some form of violence. Witnessing violence was associated with
      more behavioral problems and higher stress scores as assessed through maternal
      report. Subsequent research should examine the long-term effects of this exposure
      to violence among young children.

PMID- 11231800
TI  - Maternal depressive symptoms and emergency department use among inner-city
      children with asthma.
AB  - CONTEXT: Inner-city minority children with asthma use emergency departments (ED)
      frequently. OBJECTIVE: To examine whether maternal depressive symptoms are
      associated with ED use. DESIGN, SETTING, AND PATIENTS: Baseline and 6-month
      surveys were administered to mothers of children with asthma in inner-city
      Baltimore, Md, and Washington, DC. MAIN OUTCOME MEASURES: Use of the ED at 6
      month follow-up was examined. Independent variables included asthma morbidity,
      age, depressive symptoms, and other psychosocial data. RESULTS: Among mothers,
      nearly half reported significant levels of depressive symptoms. There were no
      demographic or asthma-related differences between the children of mothers with
      high and low depressive symptoms. However, in bivariate analyses, mothers with
      high depressive symptoms were 40% (prevalence ratio [PR], 1.4; 95% confidence
      interval [CI], 1.0-3.6; P =.04) more likely to report taking their child to the
      ED. Mothers aged 30 to 35 years were more than twice as likely (PR, 2.2; 95% CI,
      1.9-9.3; P =.001) to report ED use, as were children with high morbidity (PR,
      1.9; 95% CI, 1.4-7.1; P =.006). Child age and family income were not predictive
      of ED use. After controlling for asthma symptoms and mother's age, mothers with
      depressive symptoms were still 30% more likely to report ED use. CONCLUSIONS:
      Depression is common among inner-city mothers of children with asthma. Beyond
      asthma morbidity, maternal age and depressive symptoms are strong predictors of
      reports of ED visits. Identifying and addressing poor psychological adjustment in
      mothers may reduce unnecessary ED visits and optimize asthma management among
      inner-city children.

PMID- 11231801
TI  - Measles-mumps-rubella and other measles-containing vaccines do not increase the
      risk for inflammatory bowel disease: a case-control study from the Vaccine Safety
      Datalink project.
AB  - CONTEXT: A link between measles virus-containing vaccines and inflammatory bowel
      disease (IBD) has been suggested by recent studies. OBJECTIVE: To address whether
      receipt or timing of measles-containing vaccine (MCV) increases risk for IBD.
      DESIGN: A case-control study. SETTING: Four large health maintenance
      organizations (HMOs) that are part of the Centers for Disease Control and
      Prevention's Vaccine Safety Datalink project. PATIENTS OR OTHER PARTICIPANTS: A
      total of 155 persons with codes from International Classification of Diseases,
      Ninth Revision specific for IBD, born between 1958 and 1989 and enrolled from
      birth to the onset of disease, were identified. Up to 5 controls were matched by
      sex, HMO, and birth year. INTERVENTION: None. MAIN OUTCOME MEASURES: Risk for
      IBD, Crohn's disease, and ulcerative colitis. RESULTS: Past vaccination was not
      associated with an increased risk for Crohn's disease (odds ratio [OR] for
      measles-mumps-rubella vaccine [MMR], 0.4; 95% confidence interval [CI], 0.08
      2.0), ulcerative colitis (OR, 0.8; 95% CI, 0.18-3.56), or IBD (OR, 0.59; 95% CI,
      0.21-1.68). Risk for IBD was not increased among children vaccinated who were
      younger than 12 months (OR for MMR, 0.61; 95% CI, 0.15-2.45) or aged 12 to 18
      months (OR, 0.86; 95% CI, 0.28-2.59) relative to unvaccinated children. Children
      vaccinated with MMR who were older than 18 months were at significantly decreased
      risk for IBD (OR, 0.16; 95% CI, 0.04-0.68). Neither past vaccination nor age at
      vaccination with other MCV was associated with increased risk for Crohn's
      disease, ulcerative colitis, or IBD. Risk for Crohn's disease, ulcerative
      colitis, or IBD was not elevated in the time immediately following vaccination
      with either vaccine. CONCLUSIONS: Vaccination with MMR or other MCV, or the
      timing of vaccination early in life, did not increase the risk for IBD.

PMID- 11231802
TI  - Television watching, energy intake, and obesity in US children: results from the
      third National Health and Nutrition Examination Survey, 1988-1994.
AB  - OBJECTIVES: To examine the relationship between television watching, energy
      intake, physical activity, and obesity status in US boys and girls, aged 8 to 16
      years. METHODS: We used a nationally representative cross-sectional survey with
      an in-person interview and a medical examination, which included measurements of
      height and weight, daily hours of television watching, weekly participation in
      physical activity, and a dietary interview. Between 1988 and 1994, the Third
      National Health and Nutrition Examination Survey collected data on 4069 children.
      Mexican Americans and non-Hispanic blacks were oversampled to produce reliable
      estimates for these groups. RESULTS: The prevalence of obesity is lowest among
      children watching 1 or fewer hours of television a day, and highest among those
      watching 4 or more hours of television a day. Girls engaged in less physical
      activity and consumed fewer joules per day than boys. A higher percentage of non
      Hispanic white boys reported participating in physical activity 5 or more times
      per week than any other race/ethnic and sex group. Television watching was
      positively associated with obesity among girls, even after controlling for age,
      race/ethnicity, family income, weekly physical activity, and energy intake.
      CONCLUSIONS: As the prevalence of overweight increases, the need to reduce
      sedentary behaviors and to promote a more active lifestyle becomes essential.
      Clinicians and public health interventionists should encourage active lifestyles
      to balance the energy intake of children.

PMID- 11231803
TI  - Outcome of children identified as anemic by routine screening in an inner-city
      clinic.
AB  - BACKGROUND: Children found to be anemic on routine screening by HemoCue, a rapid
      and relatively inexpensive method of screening for hemoglobin (Hb), are often
      prescribed iron as a diagnostic tool and potential treatment for presumed iron
      deficiency anemia (IDA). We questioned this approach given the declining
      prevalence of IDA and the concomitant relative increase in other causes of
      anemia. OBJECTIVE: To evaluate the practice of Hb screening for IDA by
      determining the prevalence of anemia by HemoCue; the proportion of anemic
      patients treated with iron and followed up; the frequency of repeated Hb testing,
      additional iron studies, and iron prescriptions; and the 6-month outcomes of
      treated and untreated anemia. DESIGN: Retrospective cohort study. RESULTS: Of
      1358 children aged 9 to 36 months who underwent screening, 343 (25%) had anemia,
      defined as a Hb level of less than 110 g/L. Outpatient medical records of 334 of
      the anemic children revealed that 239 (72%) were prescribed iron while 95 (28%)
      were not prescribed iron at the first visit for anemia. Anemia follow-up rates
      were low for the prescribed and not prescribed groups: 7% vs 5% returned within 1
      month, while 37% vs 42% did not return within 6 months for follow-up. Of the
      children who were prescribed iron, 107 (71%) of 150 responded to treatment or
      anemia resolved within 6 months compared with 27 (68%) of 40 not prescribed iron.
      Children underwent repeated blood testing for measurement of Hb and complete
      blood cell count, but underwent few iron-specific studies. CONCLUSIONS: Routine
      screening for IDA by HemoCue followed by a therapeutic trial of iron was
      problematic because of a high rate of anemia in this predominantly African
      American population, low follow-up rates, and a high spontaneous resolution rate.
      Prospective studies are needed to evaluate other screening methods to
      differentiate IDA from other forms of anemia and to improve compliance and
      outcome in inner-city children.

PMID- 11231804
TI  - Significance of grunting respirations in infants admitted to a well-baby nursery.
AB  - OBJECTIVES: (1) To determine the frequency and duration of grunting in term and
      near-term newborns; (2) to determine the peripartum characteristics associated
      with grunting; and (3) to compare the short-term outcomes of newborns with and
      without grunting. DESIGN: Medical record review of all newborns admitted to a
      well-baby nursery during a 2-month period. SETTING: University well-baby nursery
      for term infants, with more than 2700 deliveries annually. MAIN OUTCOME MEASURES:
      Frequency and duration of grunting, maternal and newborn clinical
      characteristics, clinical course, and length of stay. RESULTS: Grunting
      respirations beginning during the first 4 hours of life were recorded for 81
      (17.4%) of 466 newborns. Fifty-five (68%) stopped grunting within 30 minutes of
      birth, 69 (85%) by 1 hour, and 75 (93%) by 2 hours. More mothers of grunting
      infants received intrapartum antibiotics than mothers of nongrunters (33% vs 20%;
      P =.03). More grunting infants than nongrunters received bag and mask
      resuscitation (15% vs 5%; P =.01). More chest radiographs, blood cell counts, and
      blood cultures were ordered for grunting infants, and antibiotics were more often
      given to grunting than nongrunting infants (11.1% vs 4.6%; P =.04). Grunters'
      length of stay exceeded that of nongrunters (72 vs 55 hours; P =.01), but only 3
      were transferred to a neonatal intensive care unit. CONCLUSIONS: All grunting
      infants should be carefully observed, but because nearly all otherwise healthy
      term or near-term infants will stop grunting and have a benign course, other
      interventions can be postponed for 1 or 2 hours to give the newborn a chance to
      stop grunting or show other signs of respiratory illness.

PMID- 11231805
TI  - Accuracy of a noninvasive temporal artery thermometer for use in infants.
AB  - OBJECTIVES: To assess the accuracy of a new noninvasive temporal artery (TA)
      thermometer in infants; to compare the accuracy of the TA thermometer with that
      of a tympanic thermometer, using rectal thermometry as the criterion standard;
      and to compare the tolerability of the TA thermometer with that of the tympanic
      and rectal thermometers. DESIGN: Prospective evaluation of the accuracy of TA and
      tympanic thermometry, using rectal thermometry as the criterion standard.
      SETTING: Emergency department of an urban pediatric hospital. SUBJECTS:
      Convenience sample of 304 infants younger than 1 year presenting for care. MAIN
      OUTCOME MEASURES: Temperatures were measured using TA, tympanic, and rectal
      thermometers for all infants. Agreement between TA or tympanic and rectal
      temperatures was assessed. The sensitivity and specificity of TA or tympanic
      thermometers for detecting rectal fever were determined. Discomfort scores, using
      a standardized scale, were assessed by trained observers after each temperature
      measurement was made. RESULTS: Linear regression analysis of the relation between
      TA and rectal temperatures yielded a model with a slope of 0.79 (vs a slope of
      0.68 for tympanic vs rectal temperature; P =.02) and an r of 0.83 (vs r = 0.75
      for tympanic vs rectal temperature; P<.001). Among 109 patients with a rectal
      temperature of 38 degrees C or higher, the TA thermometer had a sensitivity of
      0.66 compared with the tympanic thermometer's sensitivity of 0.49 (P<.001).
      Discomfort scores with TA thermometry were significantly lower than with rectal
      thermometry (P =.007). CONCLUSIONS: The TA thermometer has limited sensitivity
      for detecting cases of rectal fever in infants. However, the TA thermometer is
      more accurate than the tympanic thermometer in infants, and it is better
      tolerated by infants than rectal thermometry.

PMID- 11231806
TI  - Effectiveness of a practice-based intervention to increase vaccination rates and
      reduce missed opportunities.
AB  - BACKGROUND: Although provider feedback and recall/reminder systems have been
      shown to increase vaccination rates for children, little is known about the
      effectiveness of less intensive interventions. OBJECTIVE: To determine whether
      provider prompting at acute care visits in an urban hospital-based outpatient
      clinic can increase vaccination rates and decrease missed opportunities. DESIGN
      AND METHODS: Study participants, 3 years or younger, were identified from a
      managed care organization as receiving primary care at the clinic. Eligibility
      criteria included 1 or more visits to the clinic without regard to continuity of
      enrollment. Patients' vaccination records were generated at nursing triage and
      attached to the encounter sheet. Vaccination and visit data were abstracted from
      medical records, and comparisons were made between baseline (n = 521) and
      postintervention (n = 642) groups for up-to-date vaccination rates, missed
      opportunity rates, and mean numbers of visits. RESULTS: Up-to-date rates at the
      age of 24 months for 4 diphtheria and tetanus toxoids and pertussis, 3 polio, 1
      measles-mumps-rubella, 3 hepatitis B, and 3 Haemophilus influenzae type b
      vaccines changed from 70% to 78% (P =.07). Up-to-date rates increased
      significantly to 87% among the subset of children continuously enrolled in the
      managed care organization and the practice (P<.01). Overall, mean numbers of
      visits were similar. Missed opportunity rates among children not up-to-date for 4
      diphtheria and tetanus toxoids and pertussis, 3 polio, 1 measles-mumps-rubella, 3
      hepatitis B, and 3 Haemophilus influenzae type b vaccines at the age of 24 months
      declined from 65% to 45% (P =.04). Similar trends were noted at the age of 10
      months. CONCLUSIONS: In the absence of increased funding, minor changes in
      standard operating procedures may improve vaccination delivery. Further
      improvements may require efforts to ensure continuity of provider and plan
      assignment.

PMID- 11231807
TI  - Evidence for changing guidelines for routine screening for retinopathy of
      prematurity.
AB  - CONTEXT: Existing guidelines recommended by the Canadian Pediatric Society (CPS)
      and American Academy of Pediatrics (AAP) for routine screening for retinopathy of
      prematurity (ROP) remain controversial. OBJECTIVE: To determine whether current
      guidelines for routine screening for ROP should be changed. DESIGN: We examined
      data that were collected as part of a larger study of 14 neonatal intensive care
      units (NICUs) in Canada. We examined the effect of strategies using different
      birth weight (BW) and gestational age (GA) criteria for routine ROP screening,
      and performed a cost-effectiveness analysis. SETTING: The 14 NICUs (except one)
      are regional tertiary level referral centres serving geographic regions of
      Canada, and include approximately 60% of all tertiary-level NICU beds in Canada.
      PATIENTS: This large cohort included all 16 424 infants admitted to 14 Canadian
      NICUs from January 8, 1996, to October 31, 1997. INTERVENTIONS: None. MAIN
      OUTCOME MEASURE: Treatment for ROP. RESULTS: The most cost-effective strategy was
      to routinely screen only infants having a BW of 1200 g or less. This included all
      infants treated for ROP (except 1 outlier at 32 weeks GA and 1785 g BW), at a
      marginal cost per additional person with improved vision of $513 081 for
      screening patients between 28 weeks GA and 1200 g BW, compared with $1 800 039
      and $2 075 874 for using the current AAP and CPS guidelines, respectively
      (cryotherapy outcomes). Results for laser therapy were similar, but costs were
      slightly lower. This strategy reduced the number of infants screened under the
      current CPS guidelines by 46%. CONCLUSION: Screening only infants having a BW of
      1200 g or less is the most cost-effective strategy for routine ROP screening.

PMID- 11231808
TI  - Clinical, laboratory, and epidemiologic features of murine typhus in 97 Texas
      children.
AB  - OBJECTIVE: To document the clinical, laboratory, and epidemiologic
      characteristics of pediatric patients with murine typhus. DESIGN: Pediatric
      patients were diagnosed using serologic testing, and clinical, laboratory, and
      epidemiologic data were retrospectively reviewed. SETTING: Of 97 patients, 77
      (79%) were identified and treated as inpatients and 20 (21%) were treated as
      outpatients; most resided in south Texas. PATIENTS: Between 1979 and 1996,
      medical records and patient-physician interviews were available for 97 patients
      aged 16 years and younger with murine typhus. MAIN OUTCOME MEASURES: The
      frequency of clinical symptoms and signs, abnormal laboratory findings,
      epidemiologic findings, and measures of disease severity were determined.
      RESULTS: The clinical triad of fever, headache, and rash occurred in only 43
      (49%) of 87 pediatric patients throughout the illness. Musculoskeletal symptoms
      were experienced by 43% of patients, whereas gastrointestinal tract symptoms
      (nausea, vomiting, anorexia, and diarrhea) occurred in 77%. Systemic involvement
      was evident by the frequent occurrence of abnormal laboratory findings referable
      to multiple organ systems, including the liver, kidney, blood, and central
      nervous system. CONCLUSIONS: Pediatric infection by Rickettsia typhi usually
      causes mild to moderate systemic illness. In children, the median duration of
      illness was 12 days (range, 5-29 days), but severe complications were rare.
      Length of illness was significantly related to the initial diagnosis, whereas the
      interval to defervescence was related to therapy with a tetracycline or
      chloramphenicol. Early recognition and treatment is important to prevent
      prolonged morbidity.

PMID- 11231809
TI  - Impact of low birth weight on early childhood asthma in the United States.
AB  - OBJECTIVE: To estimate the independent contribution of birth weight to asthma
      prevalence among children younger than 4 years in the United States and to
      compare the magnitude of its effect on asthma between African American and white
      children. DESIGN: Cross-sectional analysis using the 1988 National Maternal
      Infant Health Survey and 1991 Longitudinal Follow-up Survey. SETTING: United
      States. PATIENTS: Eight thousand seventy-one subjects, selected from a
      randomized, systematic population-based sample and weighted to be nationally
      representative, who completed both initial and longitudinal follow-up surveys and
      reported information on asthma diagnosis. MAIN OUTCOME MEASURES: Birth weight and
      other sociodemographic factors linked to birth outcome were analyzed for
      independent association with physician-diagnosed asthma by age 3 years. RESULTS:
      The prevalence of asthma varied by birth weight category: 6.7% in children 2500 g
      or more at birth, 10.9% in children 1500 to 2499 g at birth, and 21.9% in
      children less than 1500 g at birth (very low birth weight [VLBW]) (P<.001). Some
      of the characteristics shown to be independently associated with asthma included:
      VLBW (odds ratio [OR], 2.9; 95% confidence interval [CI], 2.3-3.6), moderately
      low birth weight (OR, 1.4; 95% CI, 1.1-1.8), and African American race (OR, 1.9;
      95% CI, 1.6-2.4). In stratified analyses, the independent association between
      VLBW and asthma in white and African American populations was: OR(white), 3.1
      (95% CI, 2.2-4.3) and OR(African American), 2.5 (95% CI, 2.0-3.3). The prevalence
      of VLBW, however, was tripled in African American compared with white children
      (1.8% vs 0.6%). CONCLUSIONS: These data confirm findings of other studies that
      identify a strong independent association between low birth weight and asthma.
      For this 1988 national birth cohort, an estimated 4000 excess asthma cases were
      attributable to birth weight less than 2500 g. Although the strength of the
      independent association between VLBW and asthma was smaller in the African
      American population, the substantially increased prevalence of VLBW in this
      community may contribute to the disproportionately increased prevalence of asthma
      among African American children.

PMID- 11231810
TI  - Picture of the month. Amyoplasia congenita.

PMID- 11231811
TI  - Pathological case of the month. Primary bone lymphoma: diffuse large B-cell type.

PMID- 11231812
TI  - Pathological case of the month. Ki-1-positive anaplastic large cell lymphoma
      involving muscle.

PMID- 11231813
TI  - Radiological case of the month. Mesenteric cyst.

PMID- 11231814
TI  - Radiological case of the month. Inferior vena cava and renal vein thrombosis in a
      neonate.

PMID- 11231815
TI  - Boy Scouts of America policy on homosexuality.

PMID- 11231818
TI  - Promoting adolescent smoking cessation is worth the effort.

PMID- 11231816
TI  - Pediatric acetaminophen poisoning.

PMID- 11231820
TI  - Does information collected during the residency match process predict clinical
      performance?

PMID- 11231822
TI  - Universal newborn hearing screening.

PMID- 11231827
TI  - Depression and cardiac mortality: results from a community-based longitudinal
      study.
AB  - BACKGROUND: Depression may be a potential risk factor for subsequent cardiac
      death. The impact of depression on cardiac mortality has been suggested to depend
      on cardiac disease status, and to be stronger among cardiac patients. This study
      examined and compared the effect of depression on cardiac mortality in community
      dwelling persons with and without cardiac disease. METHODS: A cohort of 2847 men
      and women aged 55 to 85 years was evaluated for 4 years. Major depression was
      defined according to psychiatric DSM-III criteria. Minor depression was defined
      by Center for Epidemiologic Studies-Depression Scale scores of 16 or higher.
      Effects of minor and major depression on cardiac mortality were examined
      separately in 450 subjects with a diagnosis of cardiac disease and in 2397
      subjects without cardiac disease after adjusting for demographics, smoking,
      alcohol use, blood pressure, body mass index, and comorbidity. RESULTS: Compared
      with nondepressed cardiac patients, the relative risk of subsequent cardiac
      mortality was 1.6 (95% confidence interval [CI], 1.0-2.7) for cardiac patients
      with minor depression and 3.0 (95% CI, 1.1-7.8) for cardiac patients with major
      depression, after adjustment for confounding variables. Among subjects without
      cardiac disease at baseline, similar increased cardiac mortality risks were found
      for minor depression (1.5 [95% CI, 0.9-2.6]) and major depression (3.9 [95% CI,
      1.4-10.9]). CONCLUSION: Depression increases the risk for cardiac mortality in
      subjects with and without cardiac disease at baseline. The excess cardiac
      mortality risk was more than twice as high for major depression as for minor
      depression.

PMID- 11231828
TI  - Depression as a risk factor for coronary heart disease mortality.

PMID- 11231829
TI  - Childhood depression and adult personality disorder: alternative pathways of
      continuity.
AB  - BACKGROUND: This study extends previous findings of the risks posed by childhood
      major depressive disorder and other psychopathological features for later
      personality disorder (PD) in a random sample of 551 youths. METHODS: Self-reports
      and mother reports were used to evaluate DSM-III-R (Axes I and II) psychiatric
      disorders at mean ages of 12.7, 15.2, and 21.1 years. Logistic regression was
      used to examine the independent effects of major depressive disorder in childhood
      or adolescence on 10 PDs in young adulthood. RESULTS: Odds of dependent,
      antisocial, passive-aggressive, and histrionic PDs increased by more than 13, 10,
      7, and 3 times, respectively, given prior major depressive disorder. Those
      effects were independent of age, sex, disadvantaged socioeconomic status, a
      history of child maltreatment, nonintact family status, parental conflict,
      preexisting PD in adolescence, and other childhood or adolescent Axis I
      psychopathological features, including disruptive and anxiety disorders. In
      addition, odds of schizoid and narcissistic PD increased by almost 6 times and
      odds of antisocial PD increased by almost 5 times given a prior disruptive
      disorder, and odds of paranoid PD increased by 4 times given a prior anxiety
      disorder. CONCLUSION: Personality disorders may represent alternative pathways of
      continuity for major depressive disorder and other Axis I disorders across the
      child-adult transition.

PMID- 11231830
TI  - Childhood depression and conduct disorder: different routes to the same outcome?

PMID- 11231831
TI  - A randomized trial of relapse prevention of depression in primary care.
AB  - BACKGROUND: Despite high rates of relapse and recurrence, few primary care
      patients with recurrent or chronic depression are receiving continuation and
      maintenance-phase treatment. We hypothesized that a relapse prevention
      intervention would improve adherence to antidepressant medication and improve
      depression outcomes in high-risk patients compared with usual primary care.
      METHODS: Three hundred eighty-six patients with recurrent major depression or
      dysthymia who had largely recovered after 8 weeks of antidepressant treatment by
      their primary care physicians were randomized to a relapse prevention program (n
      = 194) or usual primary care (n = 192). Patients in the intervention group
      received 2 primary care visits with a depression specialist and 3 telephone
      visits over a 1-year period aimed at enhancing adherence to antidepressant
      medication, recognition of prodromal symptoms, monitoring of symptoms, and
      development of a written relapse prevention plan. Follow-up assessments were
      completed at 3, 6, 9, and 12 months by a telephone survey team blinded to
      randomization status. RESULTS: Those in the intervention group had significantly
      greater adherence to adequate dosage of antidepressant medication for 90 days or
      more within the first and second 6-month periods and were significantly more
      likely to refill medication prescriptions during the 12-month follow-up compared
      with usual care controls. Intervention patients had significantly fewer
      depressive symptoms, but not fewer episodes of relapse/recurrence over the 12
      month follow-up period. CONCLUSIONS: A relapse prevention program targeted to
      primary care patients with a high risk of relapse/recurrence who had largely
      recovered after antidepressant treatment significantly improved antidepressant
      adherence and depressive symptom outcomes.

PMID- 11231832
TI  - Social anxiety disorder and the risk of depression: a prospective community study
      of adolescents and young adults.
AB  - BACKGROUND: Social anxiety disorder (SAD) (also known as "social phobia") is
      frequently comorbid with major depression, and in such cases, almost always
      precedes it. This has led to interest in SAD as a possible modifier of the risk
      and/or course of mood disorders. METHODS: Data come from a prospective,
      longitudinal epidemiologic study of adolescents and young adults (aged 14-24
      years) in Munich, Germany. Respondent diagnoses (N = 2548) at baseline and follow
      up (34-50 months later) are considered. The influence of SAD at baseline on the
      risk, course, and characteristics of depressive disorders (ie, major depression
      or dysthymia) at follow-up is examined. RESULTS: The baseline prevalence of SAD
      was 7.2% (95% confidence interval [CI], 6.1%-8.4%). Social anxiety disorder in
      nondepressed persons at baseline was associated with an increased likelihood
      (odds ratio [OR] = 3.5; 95% CI, 2.0-6.0) of depressive disorder onset during the
      follow-up period. Furthermore, comorbid SAD and depressive disorder at baseline
      was associated with a worse prognosis (compared with depressive disorder without
      comorbid SAD at baseline). This is exemplified by the greater likelihood of
      depressive disorder persistence or recurrence (OR = 2.3; 95% CI, 1.2-4.6) and
      attempted suicide (OR = 6.1; 95% CI, 1.2-32.2). CONCLUSIONS: Social anxiety
      disorder during adolescence or young adulthood is an important predictor of
      subsequent depressive disorders. Moreover, the presence of comorbid SAD in
      adolescents who are already depressed is associated with a more malignant course
      and character of subsequent depressive illness. These findings may inform
      targeted intervention efforts.

PMID- 11231833
TI  - The genetic epidemiology of irrational fears and phobias in men.
AB  - BACKGROUND: Much of our knowledge of the role of genetic factors in the etiology
      of phobias comes from one population-based sample of female twins. We examined
      the sources of individual differences in the risks for phobias and their
      associated irrational fears in male twins. METHODS: In personal interviews with
      both members of 1198 male-male twin pairs (707 monozygotic [MZ] and 491 dizygotic
      [DZ]) ascertained from a population-based registry, we assessed the lifetime
      history of agoraphobia and social, animal, situational, and blood/injury phobias
      as well as their associated irrational fears. Twin resemblance was assessed by
      means of probandwise concordance, odds ratios, tetrachoric correlations, and
      univariate and multivariate biometrical model fitting. RESULTS: The suggestive
      results obtained by analysis of phobias only were supported by analyzing both
      fears and phobias. All 5 phobia subtypes aggregate within twin-pairs. This
      aggregation is due largely or solely to genetic factors with heritability of
      liabilities ranging from 25% to 37%. Multivariate analysis revealed a common
      genetic factor, genetic factors specific to each subtype, and a common familial
      environmental factor. CONCLUSIONS: In male subjects, genetic risk factors, which
      are partially common across all subtypes and partially subtype specific, play a
      moderate role in the etiology of phobias and their associated irrational fears.
      Family environment probably has an impact on risk for agoraphobia and social
      phobia. The genetic liability to blood/injury phobias is not distinct from those
      of the more typical phobias.

PMID- 11231834
TI  - Sleep and sleep electroencephalogram in depressed patients treated with
      phenelzine.
AB  - BACKGROUND: The beneficial effect of antidepressant interventions has been
      proposed to depend on suppression of rapid eye movement (REM) sleep or inhibition
      of electroencephalographic (EEG) slow-wave activity (SWA) in non-REM sleep. Use
      of the monoamine oxidase inhibitor phenelzine sulfate can eliminate REM sleep. We
      studied the relation between REM sleep suppression and antidepressant response
      and the effect of phenelzine therapy on sleep EEG power spectra. METHODS: Open
      labeled prescriptions of 30 to 90 mg of phenelzine were given to 11 patients with
      major depressive disorder (6 men and 5 women; mean age, 41.4 years); all were
      physically healthy. Mood, dream recall, sleep, sleep EEG, and ocular and muscular
      activity during sleep were studied before treatment and during the third and
      fifth weeks of pharmacotherapy. RESULTS: Six patients remitted from depression, 2
      responded partially, and 3 showed no antidepressant response. Independent from
      clinical response, REM sleep was dramatically suppressed. On average, only 4.9
      minutes of REM sleep was observed in treatment week 5, and it was completely
      absent in 6 patients. This effect was compensated for by increased stage 2 sleep.
      In non-REM sleep, EEG power was higher than at baseline between 16.25 and 25 Hz.
      Slow-wave activity (power within 0.75-4.5 Hz) and the exponential decline of SWA
      during sleep were not affected. CONCLUSIONS: Antidepressant response to
      phenelzine treatment does not depend on elimination of REM sleep or inhibition of
      SWA in non-REM sleep. In depressed patients, REM sleep is regulated independently
      from non-REM sleep and can be manipulated without altering the dynamics of SWA.

PMID- 11231835
TI  - Selective deficits in prefrontal cortex function in medication-naive patients
      with schizophrenia.
AB  - BACKGROUND: Previously we proposed that dorsolateral prefrontal cortex (PFC)
      supports a specific working memory (WM) subcomponent: the ability to represent
      and maintain context information necessary to guide appropriate task behavior. By
      context, we mean prior task-relevant information represented in such a form that
      it supports selection of the appropriate behavioral response. Furthermore, we
      hypothesized that WM deficits in schizophrenia reflect impaired context
      processing due to a disturbance in dorsolateral PFC. We use functional magnetic
      resonance imaging to examine PFC activation in medication-naive, first-episode
      patients with schizophrenia during a WM, task-isolating context processing.
      METHODS: Fourteen first-episode, medication-naive patients with schizophrenia and
      12 controls similar in age, sex, and parental education underwent functional
      magnetic resonance imaging during performance of an A-X version of the Continuous
      Performance Test. RESULTS: Patients with schizophrenia demonstrated deficits in
      dorsolateral PFC activation in task conditions requiring context processing but
      showed intact activation of posterior and inferior PFC. In addition, patients
      demonstrated intact activation of the primary motor and somatosensory cortex in
      response to stimulus processing demands. CONCLUSIONS: These results demonstrate
      selectivity in dorsolateral PFC dysfunction among medication-naive first-episode
      patients with schizophrenia, suggesting that a specific deficit in PFC function
      is present at illness onset, prior to the administration of medication or the
      most confounding effects of illness duration. Furthermore, these results are
      consistent with the hypothesis that WM deficits in patients with schizophrenia
      reflect an impairment in context processing due to a disturbance in dorsolateral
      PFC function.

PMID- 11231836
TI  - Quantitative brain magnetic resonance imaging in girls with attention
      deficit/hyperactivity disorder.
AB  - BACKGROUND: Anatomic studies of boys with attention-deficit/hyperactivity
      disorder (ADHD) have detected decreased volumes in total and frontal brain, basal
      ganglia, and cerebellar vermis. We tested these findings in a sample of girls
      with ADHD. METHODS: Anatomic brain magnetic resonance images from 50 girls with
      ADHD, of severity comparable with that in previously studied boys, and 50 healthy
      female control subjects, aged 5 to 15 years, were obtained with a 1.5-T scanner
      with contiguous 2-mm coronal slices and 1.5-mm axial slices. We measured volumes
      of total cerebrum, frontal lobes, caudate nucleus, globus pallidus, cerebellum,
      and cerebellar vermis. Behavioral measures included structured psychiatric
      interviews, parent and teacher ratings, and the Wechsler vocabulary and block
      design subtests. RESULTS: Total brain volume was smaller in girls with ADHD than
      in control subjects (effect size, 0.40; P =.05). As in our previous study in boys
      with ADHD, girls with ADHD had significantly smaller volumes in the posterior
      inferior cerebellar vermis (lobules VIII-X; effect size, 0.54; P =.04), even when
      adjusted for total cerebral volume and vocabulary score. Patients and controls
      did not differ in asymmetry in any region. Morphometric differences correlated
      significantly with several ratings of ADHD severity and were not predicted by
      past or present stimulant drug exposure. CONCLUSIONS: These results confirm
      previous findings for boys in the posterior-inferior lobules of the cerebellar
      vermis. The influence of the cerebellar vermis on prefrontal and striatal
      circuitry should be explored.

PMID- 11231838
TI  - Magnetic seizure therapy of major depression.

PMID- 11231837
TI  - Decreased cortisol levels in adolescent girls with conduct disorder.
AB  - BACKGROUND: Female adolescent antisocial behavior is increasing, but little is
      known about the neuroendocrinologic aspects of this disorder. On the basis of
      reports of decreased cortisol levels in antisocial males, we investigated morning
      plasma cortisol levels in adolescent girls with conduct disorder (CD). METHODS:
      Three plasma samples for cortisol levels were taken every 20 minutes between 8
      and 9 AM in 47 adolescent girls with CD (mean +/- SD age, 16.5 +/- 0.9 years) and
      37 normal control girls (mean age, 16.0 +/- 0.8 years). All blood was drawn
      within 72 hours after the onset of menstrual flow. RESULTS: Girls with CD had
      significantly lower cortisol levels than girls in the normal control group at all
      3 sampling times. This finding was not due to procedural factors, demographic
      characteristics, or the use of medications. The girls with CD who had no other
      psychiatric problems had lower cortisol levels than girls with other disorders or
      those in the normal control group. In the multiple regression analysis, having CD
      predicted 10% of the variance in cortisol levels. CONCLUSIONS: Morning plasma
      cortisol levels were significantly diminished in adolescent girls with CD.
      Decreased cortisol levels appear to be most strongly associated with antisocial
      girls who do not have other psychiatric disorders.

PMID- 11231839
TI  - Causes of posttraumatic stress disorder in psychotic patients.

PMID- 11231840
TI  - Depression during the perimenopause.

PMID- 11231841
TI  - Cognitive impairment with chronic disease in depression and mortality.

PMID- 11231843
TI  - Pedicled bone flap formation using transplanted bone marrow stromal cells.
AB  - HYPOTHESIS: Transplanted osteoprogenitor cells derived from cultured bone marrow
      stromal cells (BMSCs) can be used to fabricate pedicled bone flaps. DESIGN:
      Prospective, randomized experimental trials. SETTING: Basic science research
      laboratory. MATERIALS: Immunodeficient female NIH-Bg-Nu-Xid mice, aged 3 months.
      INTERVENTION: The BMSCs were harvested from the long bones of C57Bl/6 transgenic
      mice carrying the type Ialpha1 collagen-chloramphenicol acetyl transferase
      reporter gene construct; their numbers were expanded in tissue culture. Treated
      mice received BMSC transplantations around the common carotid artery and internal
      jugular vein, the aorta and its venae comitantes, or the saphenous artery and
      vein; control mice received a sham transplant in comparable recipient sites. MAIN
      OUTCOME MEASURES: Mice underwent harvesting from 4 weeks to 2 years after
      transplantation. Transplants were evaluated via histological,
      immunohistochemical, and angiographic analyses. RESULTS: Compared with the
      controls, which formed no bone, 32 of 37 BMSC-containing transplants formed a
      vascularized bone island that was perfused specifically and solely by its common
      carotid artery vascular source. Mature transplants consisted of well-developed
      lamellar, corticocancellous bone whose osteocytes were derived from the grafted
      BMSCs; hematopoietic tissue derived from the recipient mouse. Transplants formed
      as early as 4 weeks and remained stable in size as late as 108 weeks.
      CONCLUSIONS: Bone marrow stromal cells can be used to create vascularized bone
      flaps in mice; these bone constructs are vascularized by their pedicle and
      therefore can potentially be transferred to a recipient site using microsurgical
      techniques. These findings provide proof of principle of an additional clinical
      application of BMSC transplantation techniques.

PMID- 11231844
TI  - Small tissue bites and wound strength: an experimental study.
AB  - HYPOTHESIS: Placing stitches close to the cut wound edge does not produce low
      wound bursting strength in midline laparotomy incisions closed with a suture
      length:wound length ratio of 4. DESIGN: Experimental study in rats. METHODS:
      Midline incisions were closed with a running suture in 51 Sprague-Dawley rats. A
      suture length:wound length ratio of 4 was used and stitches were placed at a
      distance of 3, 6, or 10 mm from the wound edge. Wound bursting strength was
      studied immediately after and 4 days after wound closure. RESULTS: Immediately
      after wound closure, bursting pressure was higher with stitches placed 10 mm from
      the wound edge than those at a distance of 3 mm. After 4 days, bursting pressure
      and bursting volume were lower with stitches placed 10 mm from the wound edge
      than those at a distance of 3 or 6 mm. The abdominal wall ruptured outside the
      suture line in 14 of 17 wounds closed with 21 stitches, in 11 of 17 wounds closed
      with 16 stitches, and in 6 of 17 wounds closed with 11 stitches (P=.02).
      CONCLUSIONS: Four days after closure of midline laparotomy incisions using a
      suture length-wound length ratio of 4, wound bursting strength is higher with
      stitches placed 3 to 6 mm from the wound edge than those at a distance of 10 mm.
      Wound bursting strength increases with the number of stitches used.

PMID- 11231845
TI  - A reliable method for isolation of viable porcine islet cells.
AB  - HYPOTHESIS: Mechanical injury and oxidative stress caused by reoxygenation of
      isolated porcine islet cells result in their unresponsiveness to glucose
      stimulation. DESIGN: Adult pigs (weighing 25-30 kg) were anesthetized, and
      following intra-arterial infusion of ice-cold University of Wisconsin solution, a
      complete pancreatectomy was performed. The pancreatic duct was cannulated for
      infusion of digestion medium containing collagenase type P, 1.5 mg/mL;
      deoxyribonuclease I, 10 000 U; and a water-soluble analogue of vitamin E
      (Trolox), 1 mmol/L. After 20-minute incubations on ice, and at 37 degrees C, the
      pancreas was hand shaken for 1 minute, followed by filtration and separation on
      an automatic cell separator (COBE 2991). Islet cells, identified by dithizone
      staining, were perifused at 37 degrees C. RESULTS: The mean +/- SEM yield of
      intact purified islet cells (50-200 microm in diameter), and mostly present in
      clusters, was 2398 +/- 143 cells per gram (n = 12). Glucose stimulation caused a
      significant increase in biphasic insulin secretion in the perifusion experiments.
      CONCLUSION: We have developed a simple, reproducible, and reliable procedure for
      isolating intact and viable porcine islet cells suitable for xenotransplantation.

PMID- 11231846
TI  - Liver transplantation in rats using small-for-size grafts: a study of hemodynamic
      and morphological changes.
AB  - BACKGROUND: Damage to a small-for-size liver graft after reperfusion is
      frequently observed but the mechanism of injury remains unclear. HYPOTHESIS:
      Injury to a small-for-size liver graft is related to the changes of portal
      pressure and blood flow. MAIN OUTCOME MEASURES: Survival rates, portal
      hemodynamics, microcirculatory changes, and morphological changes (by light
      microscopy and electron microscopy). SETTING: A rat model of nonarterialized
      orthotopic liver transplantation comparing 2 groups of rats transplanted with
      whole grafts (100% of recipient liver weight) and small-for-size grafts (30% of
      recipient liver weight). RESULTS: Median survival of the rats with small-for-size
      grafts was 30 hours (range, 27-37 hours). During the first 15 minutes after
      reperfusion, mean arterial pressure of the small-for-size graft group was
      significantly lower than that of the whole graft group (10-minute: 100 vs 132 mm
      Hg, P =.04; 15-minute: 96 vs 127 mm Hg, P =.04). Portal pressure (in centimeters
      of water) of the small-for-size graft group was significantly higher in the first
      20 minutes after reperfusion than the level before the anhepatic phase (5-minute:
      15.1 vs 9.3, P =.02; 10-minute: 16.1 vs 9.3, P =.03; 15-minute, 13.5 vs 9.3, P
      =.03; 20-minute: 13.4 vs 9.3, P =.03) and was significantly higher than that of
      the whole graft group in the first 10 minutes after reperfusion (5-minute: 15.1
      vs 9.6, P =.02; 10-minute: 16.1 vs 10.3, P =.04). Hepatic microcirculatory blood
      flow (in milliliters per minute per 100 g) was also significantly higher in the
      small-for-size graft group during the first 40 minutes after reperfusion (5
      minute: 16.3 vs 9.3, P =.02; 10-minute: 14.9 vs 6.6, P =.02; 15-minute: 14.8 vs
      5.5, P =.02; 20-minute: 13.1 vs 7.0, P =.02; 30-minute: 13.2 vs 8.8, P =.04; 40
      minute: 14.6 vs 7.1, P =.02). Light and electron microscopy showed normal
      morphological features of whole graft up to 24 hours after reperfusion. The small
      for-size graft, however, showed sinusoidal congestion, tremendous swelling of
      mitochondria of hepatocytes, irregular large gap of sinusoidal lining cells, and
      collapse of the space of Disse. CONCLUSIONS: In a rat model, the portal
      hemodynamic changes in small-for-size grafts are transient. Progressive damage of
      the graft may result from microcirculatory failure due to irreversible
      endothelial injury after reperfusion.

PMID- 11231847
TI  - The case for beta-adrenergic blockade as prophylaxis against perioperative
      cardiovascular morbidity and mortality.
AB  - Perioperative morbidity and mortality are frequently cardiac in origin. Many
      studies have prospectively attempted to define risk factors for cardiac ischemic
      events. Although we can now identify high-risk patients, optimal cardioprotective
      management strategies remain unclear. Treatment with beta-adrenergic antagonists
      decreases myocardial oxygen consumption and is generally well tolerated. This
      article reviews the physiologic and clinical basis for using these agents as
      prophylaxis against cardiovascular events in high-risk surgical patients.

PMID- 11231848
TI  - Sodium hyaluronate increases the fibrinolytic response of human peritoneal
      mesothelial cells exposed to tumor necrosis factor alpha.
AB  - HYPOTHESIS: Sodium hyaluronate interferes with the fibrin degrading capacity of
      human peritoneal mesothelial cells exposed to tumor necrosis factor (TNF) alpha.
      DESIGN: Controlled laboratory experiment. INTERVENTION: Human peritoneal
      mesothelial cells were harvested from 5 patients undergoing laparotomy and
      cultured in vitro. Cells were treated with TNF-alpha, a cytokine typically
      involved in peritoneal inflammation, and sodium hyaluronate was added in a final
      concentration of 0.1%, 0.2%, or 0.4%. Controls received medium only. After 24
      hours' incubation, tissue-type plasminogen activator (tPA), urokinase-type
      plasminogen activator (uPA), and plasminogen activator inhibitor type 1 (PAI-1)
      were measured in the medium and cell lysates using enzyme-linked immunosorbent
      assay techniques. Specific gene transcripts in cells treated with 0.4% sodium
      hyaluronate and controls were determined using a quantitative reverse
      transcription polymerase chain reaction. MAIN OUTCOME MEASURES: Concentrations of
      tPA, uPA, and PAI-1, and their specific gene transcripts. RESULTS: Sodium
      hyaluronate significantly increased tPA concentration in cell lysates without
      affecting its gene expression as determined after 24 hours (P =.02). The uPA
      concentration was significantly decreased by sodium hyaluronate in the medium but
      not in cell lysates (P<.0001). The uPA messenger RNA expression was 1000-fold
      increased compared with control. Sodium hyaluronate significantly decreased PAI-1
      concentration in the medium and reduced its gene expression 500-fold (P =.04),
      while PAI-1 concentration in cell lysates did not change. CONCLUSION: Sodium
      hyaluronate affected the fibrinolytic response of TNF-alpha-stimulated human
      peritoneal mesothelial cells, most notably by decreasing PAI-1 transcription and
      release. This observation indicates that sodium hyaluronate counteracts the
      fibrinolytic decline induced by TNF-alpha and suggests a biological mechanism of
      action for sodium hyaluronate intra-abdominally.

PMID- 11231850
TI  - A prospective randomized trial on heart rate variability of the surgical team
      during laparoscopic and conventional sigmoid resection.
AB  - HYPOTHESIS: Mental strain measured by heart rate variability differs during
      laparoscopic and conventional sigmoid resections. DESIGN: Prospective randomized
      study. SETTING: University hospital. PARTICIPANTS: Two surgeons performed 10
      conventional and 10 laparoscopic sigmoid resections, alternating roles as primary
      surgeon and assistant. The kind of technique was randomly chosen each time.
      INTERVENTION: Electrocardiograms of the surgeon and assistant were continuously
      recorded during the procedures and heart rate variability was analyzed off-line.
      The first 10 procedures (5 laparoscopic and 5 conventional) were performed by the
      more experienced and the next 10 by the less experienced surgeon. MAIN OUTCOME
      MEASURES: Heart rate variability was determined by power spectral analysis as
      heart rate in beats per minute, high frequency (HF) and low frequency (LF)
      components in normalized units, and LF/HF ratio. RESULTS: Results are given for
      heart rate, HF, LF, and LF/HF ratio for the following variables: laparoscopic
      surgery: 87.9, 14.7, 90.1, 7.5; conventional surgery: 90.2, 17.1, 87.6, 6.4;
      surgeon: 94.0, 13.5, 91.4, 8.4; first assistant: 84.1, 17.8, 86.3, 5.6; more
      experienced surgeon: 93.1, 16.5, 87.8, 6.4; and less experienced surgeon: 85.0,
      14.8, 90.0, 7.5. The LF/HF ratio was significantly higher (P<.05) for
      laparoscopic compared with conventional surgery and for the surgeon compared with
      the assistant (P<.001), but not between the less and the more experienced
      surgeons. CONCLUSION: Performing laparoscopic colorectal surgery causes higher
      mental strain in surgeons than performing conventional surgery.

PMID- 11231849
TI  - Dietary restriction impairs neutrophil exudation by reducing CD11b/CD18
      expression and chemokine production.
AB  - HYPOTHESIS: Patients with malnutrition are susceptible to infection.
      Polymorphonuclear neutrophils (PMNs) are the major effector of the nonspecific
      immune response in host resistance to infection. Dietary restriction may impair
      PMN-mediated immunity in the peritoneal cavity by reducing PMN exudation,
      adhesion molecule expression on PMNs, and chemokine production. DESIGN:
      Randomized study of murine glycogen-induced peritonitis with dietary restriction.
      SETTING: University research laboratory. MATERIALS: Male C57BL/6J mice.
      INTERVENTIONS: Mice (N = 204) were assigned to ad libitum, moderate, and severe
      diet-restricted groups receiving mouse chow ad libitum (132 g/kg, 66 g/kg, and 33
      g/kg daily for 7 days, respectively). After dietary restriction with or without 1
      day of refeeding, mice were administered glycogen intraperitoneally to induce
      cell exudation. MAIN OUTCOME MEASURES: CD11b, CD18, and CD62L expressions on
      circulating PMNs, phagocytosis, and reactive oxygen intermediate production by
      exudative PMNs were measured after glycogen installation. The levels of PMN
      specific chemokine, macrophage inflammatory protein 2 (MIP-2), in peritoneal
      lavage fluid were also measured. These parameters were measured after glycogen
      installation in the refeeding experiment. RESULTS: Seven days of dietary
      restriction decreased CD11b/CD18 expression on circulating PMNs, MIP-2 levels in
      peritoneal lavage fluid, and subsequent PMN exudation into the peritoneal cavity
      early in peritonitis. Both CD11b and CD18 expression on circulating PMNs and MIP
      2 levels correlated significantly with numbers of exudative PMNs. Seven days of
      dietary restriction also impaired phagocytosis, while up-regulating reactive
      oxygen intermediate production by exudative PMNs. Only 1 day of ad libitum
      refeeding normalized CD11b/CD18 expression with PMN exudation into the peritoneal
      cavity. CONCLUSIONS: Short-term dietary restriction impairs PMN exudation into
      local inflammatory sites in murine peritonitis by reducing CD11b/CD18 expression
      and MIP-2 production. Even brief nutritional replenishment in diet-restricted
      patients may improve host defense via restoring these PMN functions and chemokine
      production at local inflammatory sites.

PMID- 11231852
TI  - A novel approach to reducing postoperative intraperitoneal adhesions through the
      inhibition of insulinlike growth factor I activity.
AB  - HYPOTHESIS: Interference with insulinlike growth factor I (IGF-I) activity, both
      systemically and intraperitoneally, reduces postoperative intraperitoneal
      adhesion severity. SETTING: Experimental animal model. DESIGN, INTERVENTIONS, AND
      MAIN OUTCOME MEASURES: Adult female rats were subjected to hypophysectomy, sham
      hypophysectomy (control), IGF binding protein 4 (IGFBP-4) treatment, or albumin
      treatment (control). All rats underwent laparotomy and uterine horn abrasion with
      adjacent parietal peritoneal trauma for the purpose of creating postoperative
      intraperitoneal adhesions. Glucocorticoids and thyroid hormone were replaced in
      the hypophysectomy group. On postoperative day 10, rats were weighed, subjected
      to phlebotomy, and killed. Postmortem laparotomies were performed and blinded
      observers scored uterine-peritoneal adhesions on a 0 to 3 scoring system. Plasma
      IGFBP-4 levels and organ weights were measured in the IGFBP-4 and albumin
      treatment groups. Blood samples in all rats were analyzed for IGF-I levels.
      RESULTS: Rats with low IGF-I levels (hypophysectomy) and inhibited IGF-I activity
      (IGFBP-4 treatment) formed significantly less severe adhesions than their control
      counterparts. As expected, rats in the hypophysectomy group displayed greater
      weight loss and lower plasma IGF-I levels than sham-treated rats. Rats treated
      with IGFBP-4 and those treated with albumin demonstrated no differences in body
      weight, organ weights, IGF-I levels, and IGFBP-4 levels. CONCLUSIONS: Both the
      reduction of systemic IGF-I levels via hypophysectomy and the inhibition of local
      intraperitoneal IGF-I activity via IGFBP-4 treatment resulted in diminished
      postoperative adhesion severity. Treatment with IGFBP-4 may play a role in
      postoperative adhesion prophylaxis in the future.

PMID- 11231853
TI  - Colorectal hepatic metastases: resection, local ablation, and hepatic artery
      infusion pump are associated with prolonged survival.
AB  - BACKGROUND: Treatment of metastatic colorectal cancer to the liver is not
      uniform. We describe the management of metastatic colorectal cancer of the liver
      at a single institution during a 10-year period. METHODS: From January 1, 1990,
      through December 31, 1999, 174 patients were identified from the tumor registry
      at the University of Alabama at Birmingham with a diagnosis of metastatic
      colorectal cancer to the liver. Patient, tumor, laboratory, operative, and
      adjuvant therapy factors were analyzed, with overall survival as the endpoint.
      Log-rank tests were used for univariate analysis, Cox-proportional hazards model
      for multivariate analysis, and Kaplan-Meier curves were used for graphical
      representation of survival. Significance was defined as P<.05. RESULTS: Median
      age was 60 years (age range, 18-92 years). Seventy-nine percent of patients had
      synchronous liver metastases at the time of diagnosis of the primary colorectal
      tumor. The primary tumor was in the colon and rectum 75% and 25% of the time,
      respectively. Of the 89 patients who underwent operation, 73 received definitive
      surgical treatment for their liver metastases. Fifty-two patients underwent
      lobectomy or wedge resection, 5 underwent cryotherapy, and 16 had a hepatic
      artery infusion pump (HAIP) inserted. Median follow-up duration of surgically
      treated patients was 26 months. Operative mortality was 1.3%. The 3-year
      actuarial survivals for patients who underwent resection, HAIP, or those with
      unresectable disease were 70 months, 32 months, and 3 months, respectively
      (P<.001). By multivariate analysis, surgical intervention, a carcinoembryonic
      antigen level less than 200 microg/L, or a low T stage of the primary tumor were
      associated with prolongation of survival. CONCLUSIONS: Surgical resection should
      be attempted for hepatic colorectal metastases, as this is associated with
      prolonged overall survival. Hepatic artery infusion pump insertion seems to
      prolong overall survival for those with unresectable hepatic metastases, but it
      is not equal to resection. Aggressive surgical management of patients with
      hepatic colorectal metastases is safe, may prolong overall survival, and
      therefore should be considered in all patients with metastases confined to the
      liver.

PMID- 11231854
TI  - Thoracolumbar immobilization for trauma patients with torso gunshot wounds: is it
      necessary?
AB  - BACKGROUND: Previous studies have suggested that patients transported by
      emergency medical services (EMS) following major trauma had a longer injury-to
      treatment interval and a higher mortality rate than their non-EMS-transported
      counterparts. HYPOTHESIS: There is little actual benefit of thoracolumbar
      immobilization for patients with torso gunshot wounds (GSW). DESIGN:
      Retrospective analysis of prospectively gathered data from the Maryland Institute
      for Emergency Medical Service Systems State Trauma Registry from July 1, 1995,
      through June 30, 1998. SETTINGS: All designated trauma centers in Maryland.
      PATIENTS: All patients with torso GSW. MAIN OUTCOME MEASURES: (1) A patient was
      considered to have benefited from immobilization if he or she had less than
      complete neurologic deficits in the presence of an unstable vertebral column, as
      shown by the need for operative stabilization of the vertebral column; (2)
      mortality. RESULTS: There were 1000 patients with torso GSW. Among them, 141
      patients (14.1%) had vertebral column and/or spinal cord injuries. Two patients
      (0.2%) (95% confidence interval, -0.077% to 0.48%) required operative vertebral
      column stabilization, while 6 others required other spinal operations for
      decompression and/or foreign body removal. The presence of vertebral column
      injury was actually associated with lower mortality (7.1% vs 14.8%, P<.02).
      CONCLUSIONS: This study suggests that thoracolumbar immobilization is almost
      never beneficial in patients with torso GSW, and that a higher mortality rate
      existed among those GSW patients without vertebral column injury vs those with
      such injuries. The role of formal thoracolumbar immobilization for patients with
      torso GSW should be reexamined.

PMID- 11231856
TI  - Effects of preoperative steroid administration on surgical stress in hepatic
      resection: prospective randomized trial.
AB  - HYPOTHESIS: Preoperative administration of methylprednisolone sodium succinate
      can control surgical stress in patients undergoing hepatic resection. DESIGN: A
      prospective randomized trial. SETTING: A university hospital department of
      surgery. PATIENTS: Thirty-three patients who underwent hepatic resection were
      classified into 2 groups: a control group (n = 16) and a steroid group (n = 17)
      in which patients were intravenously administered 500 mg of methylprednisolone 2
      hours before surgery. MAIN OUTCOME MEASURES: Perioperative levels of interleukin
      (IL)-6 and IL-10 (serum and peritoneal), immunosuppressive acidic protein,
      Candida antigen, and other laboratory and clinical variables were measured.
      RESULTS: Postoperative levels of serum and peritoneal IL-6 and levels of C
      reactive protein were significantly lower in the steroid group than in controls.
      Furthermore, serum and peritoneal IL-10 levels were significantly higher in the
      steroid group. The total bilirubin value on postoperative day 1 was significantly
      lower in the steroid group than in controls. Postoperative immunosuppressive
      acidic protein levels were also significantly lower in the steroid group, as was
      the positive rate of serum Candida antigen. No differences were found in the
      incidence of postoperative complications. CONCLUSIONS: Preoperative steroid
      administration significantly elevated anti-inflammatory cytokine IL-10 levels,
      suppressed the levels of inflammatory cytokines IL-6 and C-reactive protein, and
      prevented postoperative elevation of total bilirubin values. Furthermore,
      postoperative elevation of immunosuppressive acidic protein levels and the
      positive rate of Candida antigen were suppressed, indicating that the immune
      response was maintained by preoperative steroid administration.

PMID- 11231857
TI  - Ultrasonographic characteristics of thyroid nodules: prediction of malignancy.
AB  - BACKGROUND: High-resolution real-time ultrasonography (US) can detect
      characteristics of thyroid nodules, but the US differentiation between malignant
      nodules and benign nodules is not well described. HYPOTHESIS: Ultrasonography is
      useful for predicting malignancy of thyroid nodules. DESIGN: A retrospective
      study of 329 thyroid nodules (> or =5 mm) in 309 patients comparing US
      characteristics and pathological results. SETTING: A center for the treatment of
      thyroid diseases where about 1400 thyroid operations are performed per year.
      PATIENTS: Between January 1 and June 30, 1999, 309 patients were examined by US
      before thyroidectomy. MAIN OUTCOME MEASURE: The US characteristics to predict
      malignancy for both follicular and nonfollicular neoplasms by means of multiple
      logistic regression analysis. RESULTS: The sensitivity of preoperative US
      diagnosis was 86.5% for nonfollicular neoplasms and 18.2% for follicular
      neoplasms. The specificity was 92.3% and 88.7%, respectively. According to
      multiple logistic regression analysis, margin, shape, echo structure,
      echogenicity, and calcification were reliable indication of malignancy in
      nonfollicular neoplasms. According to a receiver operating characteristic curve
      constructed from this multiple logistic regression analysis, the best point not
      to overlook malignancy is the point at which sensitivity is 94% and specificity
      is 87%. The probability of malignancy at this point is greater than 0.2. For
      follicular neoplasms, ultrasonographic diagnosis was unreliable, even when
      multiple logistic regression analysis was applied. CONCLUSION: We can predict
      malignancy of nonfollicular neoplasms of the thyroid by using multiple logistic
      regression analysis based on only 5 features: margin, shape, echo structure,
      echogenicity, and calcification.

PMID- 11231858
TI  - Temporary transverse colostomy vs loop ileostomy in diversion: a case-matched
      study.
AB  - HYPOTHESIS: For temporary fecal diversion, transverse colostomy (TC) has superior
      safety, but loop ileostomy (LI) has superior management qualities. METHODS: Of
      patients with TC or LI seen between 1988 and 1997, 63 patients were matched for
      diagnosis, operative procedure, and date of surgery. The 2 groups were then
      compared for hospital/postoperative mortality and morbidity and stoma
      complications. RESULTS: Mortality rates were 6.3% for the TC group and 1.6% for
      the LI group (P =.25). Morbidity rates for stoma creation and for stoma closure
      were 47.6% and 10% (P =.19), respectively, for the TC group, and 36.5% and 6.3%
      (P>.99), respectively, for the LI group. Most morbidity events were minor, and
      neither procedure-related nor other medical complications showed a significant
      difference between the groups. However, patients with a TC were significantly
      more likely to experience skin trouble around the stoma (TC vs LI, 15.9% vs 3.2%)
      and leakage around the stoma (TC vs LI, 12.7% vs 1.6%). CONCLUSIONS: Regarding
      safety, TC and LI should be considered equivalent options for temporary fecal
      diversion. We recommend further study comparing the 2 procedures with regard to
      patient perception and quality of life.

PMID- 11231859
TI  - Improved survival and local control after intraoperative radiation therapy and
      postoperative radiotherapy: a multivariate analysis of 46 patients undergoing
      surgery for pancreatic head cancer.
AB  - HYPOTHESIS: Despite aggressive approaches, locoregional tumor control and
      survival rates for patients with cancer of the pancreatic head remain
      disappointing. In the present study, we address whether intraoperative and
      adjuvant radiotherapy may improve the prognosis for these patients. DESIGN: A
      retrospective study. SETTING: University hospital. PATIENTS: From February 1985
      to December 1995, 46 patients with an adenocarcinoma of the pancreatic head
      underwent pancreatic resection. The last 26 patients also received intraoperative
      radiotherapy (except 5 patients) and adjuvant external beam radiation therapy.
      MAIN OUTCOME MEASURES: Demographic data, tumor characteristics, surgical
      procedures, 5-year survival, and local control of disease were analyzed
      retrospectively. RESULTS: The morbidity rate was not increased by adjuvant
      radiation therapy; it was 43% in patients treated with surgery alone and 57% in
      patients treated with surgery and radiotherapy (P =.1); operative mortality was
      8% (n = 2) and 9% (n = 2), respectively (P =.8). Overall 5-year survival and
      local control were 13% and 48.6%, respectively. The mean +/- SD 5-year survival
      was 5.5% +/- 5.3% (median, 10.8 months) in the surgery-alone group and 15.7% +/-
      8.6% (median, 14.3 months) in the surgery plus radiotherapy group (P =.06); local
      control at 5 years was 29.8% +/- 16.9% and 58.4% +/- 19.9%, respectively (P<.01).
      Median metastasis-free survival was 8 and 9 months, respectively (P =.52).
      Multivariate analysis showed that adjuvant radiotherapy was an independent
      prognostic factor for survival (P<.01) and local control of the disease (P =.03).
      CONCLUSION: The present study supports the role of radiotherapy combined with
      pancreatoduodenectomy for treatment of cancer of the pancreatic head because even
      if the improvement in overall survival is moderate, it is effective in improving
      the local control of the tumor.

PMID- 11231860
TI  - The surgical aspects of the totally implantable hepatic artery infusion pump.
AB  - The design of a totally implantable hepatic artery infusion pump in 1969 made the
      use of hepatic artery infusion feasible and practical as a treatment for patients
      with hepatic neoplasms. The implantable pumps could function for long periods and
      reliably infuse a measured quantity of drug into the hepatic artery in a
      continuous fashion. This enabled oncologists to give much higher doses of
      chemotherapy directly into the blood supply of the tumors as well as to use a
      continuous infusion schedule.

PMID- 11231861
TI  - APACHE II scoring: is it time for a moratorium? Acute Physiology and Chronic
      Health evaluation.

PMID- 11231862
TI  - Image of the month. Esophageal perforation (Boerhaave syndrome).

PMID- 11231863
TI  - Some thoughts on breast cancer.

PMID- 11231864
TI  - John Benjamin Murphy, 1857-1916.

PMID- 11231865
TI  - The use of anabolic agents in HIV disease.
AB  - Anabolic steroids are synthetic analogues of the natural androgenic 'male'
      hormone called testosterone that is produced primarily in the testes in males and
      in the ovaries in females. Anabolic steroids and other agents are fast becoming
      part of the standard of care for HIV disease, gaining acceptance in reversing
      loss of lean body mass, increasing muscle strength, improving sexual functioning
      and appetite and creating a general sense of well-being. This article will review
      commonly prescribed anabolic agents, discuss potential side effects and
      contraindications.

PMID- 11231866
TI  - Antiretroviral resistance in clinical practice.
AB  - Despite the success of potent combination therapy against HIV, a large proportion
      of patients experiences treatment failure. Due to the high degree of plasticity
      of the HIV genome, ongoing virus replication in the presence of drug pressure
      will result in the selection of virus mutants with reduced drug susceptibility.
      As a result, antiretroviral drug-resistance is a common denominator in treatment
      failure. Two methods, genotyping and phenotyping, are commercially available for
      measuring resistance in clinical samples. Whereas genotyping detects resistance
      conferring mutations in the HIV reverse transcriptase and protease genes, the
      recombinant virus assay is a newly developed phenotyping technique which
      determines drug-susceptibility in a virus culture assay. With both methods,
      result interpretation remains challenging. Retrospective studies and randomized
      controlled clinical trials support the clinical utility of resistance testing in
      the setting of treatment failure. The optimal applications of resistance testing
      in a variety of other clinical settings remain to be defined.

PMID- 11231867
TI  - Does the extract of the plant Echinacea purpurea influence the clinical course of
      recurrent genital herpes?
AB  - An increasing proportion of the population perceive complementary medicine as a
      safer alternative for non-life threatening conditions such as genital herpes. The
      extract of the plant Echinacea purpurea (Echinaforce) has been shown to have
      immunomodulating properties and has been advocated in the lay press for the
      treatment of genital herpes. This study, a single centre, prospective, double
      blind, placebo-controlled cross-over trial set out to assess whether an extract
      of the plant and root of E. purpurea can prevent or decrease the frequency and
      severity of genital herpes recurrences. These were assessed using a detailed
      history and clinical review of symptoms. Visual analogue scales were used for
      documentation and haematological and immunological parameters were measured. Over
      a one-year period, 50 patients took part in the study receiving 6 months' placebo
      and 6 months' Echinaforce each. No statistically significant benefit could be
      detected in this study comparing placebo versus Echinaforce in the treatment of
      frequently recurrent genital herpes.

PMID- 11231868
TI  - A comparative study of cervical cytology, colposcopy and PCR for HPV in female
      sex workers in Singapore.
AB  - This study examined the prevalence of human papillomavirus (HPV) infection in a
      cohort of female sex workers in Singapore. HPV infection was diagnosed by
      clinical examination, Papanicolaou (Pap) smears, histology and polymerase chain
      reaction (PCR). One hundred and eighty-seven female sex workers who came for
      their routine medical screening were enrolled into the study. PCR was positive
      for HPV in 27 (14.4%), 20 of these had a single HPV type detected, while 7 had
      multiple types of HPV detected. The most common HPV types identified were types
      16, 58 and 18. In conclusion, HPV infection is moderately prevalent among sex
      workers as tested by PCR, but routine screening with Pap smears does not appear
      to be a sensitive method of diagnosis for HPV infection.

PMID- 11231869
TI  - Negotiated safety and other agreements between men in relationships: risk
      practice redefined.
AB  - This study examines patterns of agreement, knowledge and practice which can
      prevent or facilitate HIV transmission among men who are in regular ('primary')
      male-to-male relationships. Data are from a national volunteer phone-in survey of
      homosexually-active men in Australia. A sub-sample of 1070 men from a larger
      sample (n=3039) were found to have one or more regular partners for longer than 6
      months. Self-reported HIV serostatus of survey participant and his regular
      partner, type of agreement regarding anal intercourse both within and outside the
      regular relationship, and engaging in unprotected anal intercourse with regular
      and with casual partners were examined. Risk practice was defined as unprotected
      anal intercourse with a regular partner of different or unknown serostatus and/or
      unprotected anal intercourse with a casual partner. Agreements were classified
      as: negotiated safety (28.8%); no unprotected anal intercourse (33.6%); unsafe
      (10.6%) and no agreement (17.0%). Risk practice was reported by 17.8% of the men.
      Type of agreement was found to be the strongest predictor of risk practice.
      Negotiated safety agreements were common, and were kept on the whole. Men with
      unsafe agreements, although only a small proportion of men in relationships, had
      high levels of risk practice.

PMID- 11231870
TI  - Cervical smears: comparison of knowledge and practice of a general practice
      sample with a high-risk group.
AB  - Successful cervical screening programmes depend on the participation of an
      informed target population. A national cervical screening programme is shortly to
      be introduced in the Republic of Ireland. We compare the knowledge, attitudes and
      practice of 395 Irish urban women with 323 high-risk women, genitourinary
      medicine (GUM) clinic attenders. There was little difference in knowledge between
      the 2 groups. Fifty-five per cent of the general practice (GP) sample and 45% of
      the GUM sample correctly identified the purpose of a smear. Eighty-three per cent
      of both groups had had at least one smear but only 59% of the high-risk group had
      had a smear before attending the GUM clinic. Both groups expressed a preference
      for a female provider. Socio-economic grouping is the strongest predictor of
      knowledge and uptake of cervical smears and high-risk women were less likely to
      have opportunistic cervical smears. Information programmes to encourage
      participation in screening programmes must build on pre-existing knowledge and
      focus on the relevance and acceptability of the test.

PMID- 11231871
TI  - Characteristics of Vilnius street prostitutes.
AB  - Women prostituting in Vilnius City, Lithuania, were studied with regard to their
      socioeconomic background, drug and alcohol abuse, conditions for prostituting and
      for the carrier rate of sexually transmitted infectious agents. The 73 women
      studied represented a group of low-socioeconomic prostitutes with a great age
      span, i.e. 14-52 years. Forty-five per cent had one or more children. Roughly one
      third were part-time prostitutes. Some had been trafficking for more than one
      decade. Some started trafficking at the age of 13, while the other extreme was a
      woman who began to prostitute at 51 years of age. This group of Vilnius street
      walkers had few customers per day. Eighteen were intravenous drug users and
      almost all abused alcohol. All, but one, had one or more sexually transmitted
      infections (STIs). Syphilis was diagnosed in 8 (13%) and another 10 (16%) had a
      serological scar of such an infection. HIV infections were not diagnosed. Condoms
      were not consistently used during their social contacts.

PMID- 11231872
TI  - Sexual practices of HIV discordant and concordant couples in Rwanda: effects of a
      testing and counselling programme for men.
AB  - As part of a longitudinal investigation, the husbands and cohabiting male
      partners of 684 Rwandan women were recruited to participate in an HIV testing and
      counselling programme. All of the women and 256 of the men (37%) had previously
      received standard testing and generic counselling services. In this project, all
      of the men participated in an extensive, male-focused counselling programme. This
      included 428 men who were receiving testing and counselling for the first time.
      Interview responses indicated that rates of condom use during sexual intercourse
      increased dramatically at the one-year follow-up assessment for the
      serodiscordant couples. This effect was especially strong for couples whose male
      partners were receiving testing and counselling for the first time. Rates of
      condom use also increased substantially in seroconcordant HIV-positive couples
      whose partners had both been tested previously. Women in couples with at least
      one seropositive partner reported lower rates of coercive sex by their male
      partners after they completed the counselling programme. Male-focused and couple
      focused testing and counselling programmes appear to be effective in reducing
      risky sexual behaviours in heterosexual couples, even if one or both partners
      have received testing and counselling services previously.

PMID- 11231873
TI  - A rural HIV epidemic in Zimbabwe? Findings from a population-based survey.
AB  - The aim of the study was to use population-based data from 689 adults to describe
      the socio-demographic, behavioural and biomedical correlates of HIV infection and
      aid identification of effective HIV control strategies for rural Zimbabwe. Dried
      blood spot and urine samples were collected for HIV and sexually transmitted
      disease (STD) testing and participants were interviewed on socio-demographic
      characteristics, sexual behaviour and experience of STD symptoms. HIV
      seroprevalence was 23.3% and was higher in females, divorcees, widows, working
      men, estate residents, and respondents reporting histories of STD symptoms.
      Female HIV seroprevalence rises sharply at ages 16-25. A third of sexually-active
      adults had experienced STD-associated symptoms but there were delays in seeking
      treatment. Herpes simplex virus type 2 (HSV-2) and Trichomonas vaginalis are more
      common causes than syphilis, gonorrhoea, and chlamydia, and are strongly
      associated with HIV infection. Local programmes promoting safer sexual behaviour
      and fast and effective STD treatment among young women, divorcees and working men
      could reduce the extensive HIV transmission in rural communities.

PMID- 11231874
TI  - Predicting perinatal HIV infection in young Brazilian infants: How accurate are
      signs, symptoms and immunological abnormalities?
AB  - Early identification of infants perinatally infected with HIV (HIV+) requires
      costly laboratory tests which are not widely available in countries with limited
      resources. We evaluated the utility of detection of non-specific HIV-related
      signs and symptoms and immunological abnormalities in the diagnosis of perinatal
      HIV infection in Brazilian infants younger than 10 months of age and followed
      from birth. A total of 27 HIV+ and 43 uninfected infants were studied. All
      infants exhibited one or more non-specific HIV-related findings at least once.
      HIV+ infants were more frequently symptomatic than HIV- infants only when older
      than 3 months. Combinations of clinical and immunological findings resulted in
      high sensitivity (85-100%) and low specificity (25-65%) rates for the diagnosis
      of HIV infection. Conversely, low CD4+ cell counts and hyperimmunoglobulinaemia
      showed low sensitivity (52%) and high specificity (100%) rates. In conclusion,
      the detection of similar findings in HIV- and HIV+ infants underscores the need
      of early confirmatory laboratory testing.

PMID- 11231875
TI  - Management of Chlamydia trachomatis genital tract infection in Genitourinary
      Medicine clinics in the United Kingdom's North Thames Region 1999.
AB  - Assessment of clinical management of Chlamydia trachomatis genital tract
      infection was made, with particular regard to the UK National Guideline.
      Questionnaires for self-completion, mailed to lead clinicians in 31 Genitourinary
      Medicine (GUM) clinics in the North Thames Region between May and June 1999,
      focused on policies and practice. Audit of actual management of up to 10 most
      recent cases (5 male and 5 female) attending each clinic within the past 2 years
      was also undertaken. Twenty-two units (71% response) completed the survey
      questionnaire and 23 units (74% response) audited a total of 229 cases
      (males=108, females=118, sex not stated=3). Findings indicate that GUM clinics
      are managing these infections largely as recommended in the national guideline.
      Nucleic acid amplification techniques will supersede established diagnostic tests
      for GUM clinics in North Thames, increasing costs for the service, but also
      sensitivity of detection.

PMID- 11231876
TI  - An audit of the 'two glass' test of urethritis.

PMID- 11231877
TI  - Alterations in osteoclast morphology following long-term 17beta-estradiol
      administration in the mouse.
AB  - BACKGROUND: Although the role of the osteoclast in bone resorption is becoming
      better understood, much remains to be learned about osteoclastogenesis and the
      exact mechanism of action of anti-resorbing agents such as 17beta-estradiol. This
      study investigated bone and morphologic osteoclast alterations following long
      term estrogen administration to the B6D2F1 mouse. B6D2F1 mice aged 4-5 weeks were
      exposed to high levels of estrogen via implanted silastic tubing for at least 12
      weeks; controls received empty tubing. Femurs of control and treated mice were
      assessed with radiology, quantitative histomorphometry and transmission electron
      microscopy. RESULTS: After 8 weeks of treatment, there was radiologic evidence of
      severe osteosclerosis and 86% of femoral marrow space was replaced with bone.
      After 12 weeks histologic studies of treated animals revealed that osteoclasts
      were positive for tartrate-resistant acid phosphatase but showed markedly
      abnormal ultrastructure which prevented successful bone resorption. CONCLUSIONS:
      Findings extend our understanding of osteoclast structure and function in the
      mouse exposed in vivo to high doses of estrogen. Ultrastructural examination
      showed that osteoclasts from estrogen-treated mice were unable to seal against
      the bone surface and were unable to form ruffled borders.

PMID- 11231878
TI  - Characterization of DNA binding, transcriptional activation, and regulated
      nuclear association of recombinant human NFATp.
AB  - BACKGROUND: NFATp is one member of a family of transcriptional activators whose
      nuclear accumulation and hence transcriptional activity is regulated in mammalian
      cells. Human NFATp exists as a phosphoprotein in the cytoplasm of naive T cells.
      Upon antigen stimulation, NFATp is dephosphorylated, accumulates in nuclei, and
      functions to regulate transcription of genes including those encoding cytokines.
      While the properties of the DNA binding domain of NFATp have been investigated in
      detail, biochemical studies of the transcriptional activation and regulated
      association with nuclei have remained unexplored because of a lack of full
      length, purified recombinant NFATp. RESULTS: We developed methods for expressing
      and purifying full length recombinant human NFATp that has all of the properties
      known to be associated with native NFATp. The recombinant NFATp binds DNA on its
      own and cooperatively with AP-1 proteins, activates transcription in vitro, is
      phosphorylated, can be dephosphorylated by calcineurin, and exhibits regulated
      association with nuclei in vitro. Importantly, activation by recombinant NFATp in
      a reconstituted transcription system required regions of the protein outside of
      the central DNA binding domain. CONCLUSIONS: We conclude that NFATp is a bona
      fide transcriptional activator. Moreover, the reagents and methods that we
      developed will facilitate future studies on the mechanisms of transcriptional
      activation and nuclear accumulation by NFATp, a member of an important family of
      transcriptional regulatory proteins.

PMID- 11231880
TI  - The vitamin D receptor polymorphism in the translation initiation codon is a risk
      factor for insulin resistance in glucose tolerant Caucasians.
AB  - BACKGROUND: Although vitamin D receptor (VDR) polymorphisms have been shown to be
      associated with abnormal glucose metabolism, the reported polymorphisms are
      unlikely to have any biological consequences. The VDR gene has two potential
      translation initiation sites. A T-to-C polymorphism has been noted in the first
      ATG (f allele), abolishing the first translation initiation site and resulting in
      a peptide lacking the first three amino acids (F allele). We examined the role of
      this polymorphism in insulin sensitivity and beta cell function. This study
      included 49 healthy Caucasian subjects (28 females, age 28 +/- 1 years old, body
      mass index 24.57 +/- 0.57 kg/m2, waist-hip ratio 0.81 +/- 0.01 cm/cm). They were
      all normotensive (less than 140/90 mmHg) and glucose tolerant, which was
      determined by a standard 75-gm oral glucose tolerance test. Their beta cell
      function (%B) and insulin sensitivity (%S) were calculated based on the
      Homeostasis Model Assessment (HOMA). Their genotypes were determined by a
      polymerase chain reaction-restriction fragment length polymorphism analysis.
      Phenotypes were compared between genotypic groups. RESULTS: There were 18 FF, 21
      Ff, and 10 ff subjects. Since only 10 ff subjects were identified, they were
      pooled with the Ff subjects during analyses. The FF and Ff/ff groups had similar
      glucose levels at each time point before and after a glucose challenge. The Ff/ff
      group had higher insulin levels than the FF group at fasting (P=0.006), 30
      minutes (P=0.009), 60 minutes (P=0.049), and 90 minutes (P=0.042). Furthermore,
      the Ff/ff group also had a larger insulin area under the curve than the FF group
      (P=0.009). While no difference was noted in %B, the Ff/ff group had a lower %S
      than the FF group (0.53 vs. 0.78, P=0.006). A stepwise regression analysis
      confirmed that the Fok I polymorphism was an independent determinant for %S,
      accounting for 29.3% of variation in %S when combined with waist-hip ratio.
      CONCLUSIONS: We report that the Fok I polymorphism at the VDR gene locus is
      associated with insulin sensitivity, but has no influence on beta cell function
      in healthy Caucasians. Although this polymorphism has been shown to affect the
      activation of vitamin D-dependent transcription, the molecular basis of the
      association between this polymorphism and insulin resistance remains to be
      determined.

PMID- 11231879
TI  - Polyethyleneimine-mediated transfection of cultured postmitotic neurons from rat
      sympathetic ganglia and adult human retina.
AB  - BACKGROUND: Chemical methods of transfection that have proven successful with
      cell lines often do not work with primary cultures of neurons. Recent data,
      however, suggest that linear polymers of the cation polyethyleneimine (PEI) can
      facilitate the uptake of nucleic acids by neurons. Consequently, we examined the
      ability of a commercial PEI preparation to allow the introduction of foreign
      genes into postmitotic mammalian neurons. Sympathetic neurons were obtained from
      perinatal rat pups and maintained for 5 days in vitro in the absence of
      nonneuronal cells. Cultures were then transfected with varying amounts of a
      plasmid encoding either E. coli beta-galactosidase or enhanced green fluorescence
      protein (EGFP) using PEI. RESULTS: Optimal transfection efficiency was observed
      with 1 microg/ml of plasmid DNA and 5 microg/ml PEI. Expression of beta
      galactosidase was both rapid and stable, beginning within 6 hours and lasting for
      at least 21 days. A maximum yield was obtained within 72 hours with approximately
      9% of the neurons expressing beta-galactosidase, as assessed by both
      histochemistry and antibody staining. Cotransfection of two plasmids encoding
      reporter genes was achieved. Postmitotic neurons from adult human retinal
      cultures also demonstrated an ability to take up and express foreign DNA using
      PEI as a vector. CONCLUSIONS: These data suggest that PEI is a useful agent for
      the stable expression of plasmid-encoded genes in neuronal cultures.

PMID- 11231881
TI  - A case-control study of autism and mumps-measles-rubella vaccination using the
      general practice research database: design and methodology.
AB  - BACKGROUND: An association between mumps-measles-rubella (MMR) vaccination and
      the onset of symptoms typical of autism has recently been suggested. This has led
      to considerable concern about the safety of the vaccine. METHODS: A matched case
      control study using data derived form the United Kingdom General Practice
      Research Database. Children with a possible diagnosis of autism will be
      identified from their electronic health records. All diagnoses will be validated
      by a detailed review of hospital letters and by using information derived from a
      parental questionnaire. Ten controls per case will be selected from the database.
      Conditional logistic regression will be used to assess the association between
      MMR vaccination and autism. In addition case series analyses will be undertaken
      to estimate the relative incidence of onset of autism in defined time intervals
      after vaccination. The study is funded by the United Kingdom Medical Research
      Council. DISCUSSION: Electronic health databases offer tremendous opportunities
      for evaluating the adverse effects of vaccines. However there is much scope for
      bias and confounding. The rigorous validation of all diagnoses and the collection
      of additional information by parental questionnaire in this study are essential
      to minimise the possibility of misleading results.

PMID- 11231882
TI  - Human disc cells in monolayer vs 3D culture: cell shape, division and matrix
      formation.
AB  - BACKGROUND: The relationship between cell shape, proliferation, and extracellular
      matrix (ECM) production, important aspects of cell behavior, is examined in a
      little-studied cell type, the human annulus cell from the intervertebral disc,
      during monolayer vs three-dimensional (3D) culture. RESULTS: Three experimental
      studies showed that cells respond specifically to culture microenvironments by
      changes in cell shape, mitosis and ECM production: 1) Cell passages showed
      extensive immunohistochemical evidence of Type I and II collagens only in 3D
      culture. Chondroitin sulfate and keratan sulfate were abundant in both monolayer
      and 3D cultures. 2) Cells showed significantly greater proliferation in monolayer
      in the presence of platelet-derived growth factor compared to cells in 3D. 3)
      Cells on Matrigel(tm)-coated monolayer substrates became rounded and formed
      nodular colonies, a finding absent during monolayer growth. CONCLUSIONS: The
      cell's in vivo interactions with the ECM can regulate shape, gene expression and
      other cell functions. The shape of the annulus cell changes markedly during life:
      the young, healthy disc contains spindle shaped cells and abundant collagen. With
      aging and degeneration, many cells assume a strikingly different appearance,
      become rounded and are surrounded by unusual accumulations of ECM products. In
      vitro manipulation of disc cells provides an experimental window for testing how
      disc cells from given individuals respond when they are grown in environments
      which direct cells to have either spindle- or rounded-shapes. In vitro assessment
      of the response of such cells to platelet-derived growth factor and to
      Matrigel(tm) showed a continued influence of cell shape even in the presence of a
      growth factor stimulus. These findings contribute new information to the
      important issue of the influence of cell shape on cell behavior.

PMID- 11231883
TI  - A direct method to visualise the aryl acylamidase activity on cholinesterases in
      polyacrylamide gels.
AB  - BACKGROUND: In vertebrates, two types of cholinesterases exist,
      acetylcholinesterase and butyrylcholinesterase. The function of
      acetylcholinesterase is to hydrolyse acetylcholine, thereby terminating the
      neurotransmission at cholinergic synapse, while the precise physiological
      function of butyrylcholinesterase has not been identified. The presence of
      cholinesterases in tissues that are not cholinergically innervated indicate that
      cholinesterases may have functions unrelated to neurotransmission. Furthermore,
      cholinesterases display a genuine aryl acylamidase activity apart from their
      predominant acylcholine hydrolase activity. The physiological significance of
      this aryl acylamidase activity is also not known. The study on the aryl
      acylamidase has been, in part hampered by the lack of a specific method to
      visualise this activity. We have developed a method to visualise the aryl
      acylamidase activity on cholinesterase in polyacrylamide gels. RESULTS: The o
      nitroaniline liberated from o-nitroacetanilide by the action of aryl acylamidase
      activity on cholinesterases, in the presence of nitrous acid formed a diazonium
      compound. This compound gave an azo dye complex with N-(1-napthyl)
      ethylenediamine, which appeared as purple bands in polyacrylamide gels. Treating
      the stained gels with trichloroacetic acid followed by Tris-HCl buffer helped in
      fixation of the stain in the gels. By using specific inhibitors for
      acetylcholinesterase and butyrylcholinesterase, respectively, differential
      staining for the aryl acylamidase activities on butyrylcholinesterase and
      acetylcholinesterase in a sample containing both these enzymes has been
      demonstrated. A linear relationship between the intensity of colour developed and
      activity of the enzyme was obtained. CONCLUSIONS: A novel method to visualise the
      aryl acylamidase activity on cholinesterases in polyacrylamide gels has been
      developed.

PMID- 11231884
TI  - In vitro production of peroxynitrite by haemocytes from marine bivalves: C-ELISA
      determination of 3-nitrotyrosine level in plasma proteins from Mytilus
      galloprovincialis and Crassostrea gigas.
AB  - BACKGROUND: Peroxynitrite is increasingly proposed as a contributor to defence
      system in marine bivalve. It can be formed by combination of superoxide and
      nitric oxide, and can react with tyrosine residues of proteins giving rise to 3
      nitrotyrosine. RESULTS: The present article describes a competitive ELISA for the
      measurement of 3-nitrotyrosine contents of plasma proteins from marine bivalves
      by means of a monoclonal anti 3-nitrotyrosine antibody mouse IgG. CONCLUSIONS:
      This assay is sensitive enough to determine the amounts of 3-nitrotyrosine in
      plasma proteins from one animal only. Using the C-ELISA, we have shown that the
      phagocytosis of zymosan particles increased the 3-nitrotyrosine levels of plasma
      proteins from mussel M. galloprovincialis and oyster C. gigas 5.8 and 7.5 times
      respectively.

PMID- 11231885
TI  - Using evidence from different sources: an example using paracetamol 1000 mg plus
      codeine 60 mg.
AB  - BACKGROUND: Meta-analysis usually restricts the information pooled, for instance
      using only randomised, double-blind, placebo-controlled trials. This neglects
      other types of high quality information. This review explores using different
      information for the combination of paracetamol 1000 mg and codeine 60 mg in acute
      postoperative pain. RESULTS: Randomised, double-blind, placebo-controlled trials
      of paracetamol 1000 mg and codeine 60 mg had an NNT of 2.2 (95% confidence
      interval 1.7 to 2.9) for at least 50% pain relief over four to six hours in three
      trials with 197 patients. Computer simulation of randomised trials demonstrated
      92% confidence that the simulated NNT was within +/- 0.5 of the underlying value
      of 2.2 with this number of patients. The result was supported a rational dose
      response relationship for different doses of paracetamol and codeine in 17
      additional trials with 1,195 patients. Three controlled trials lacking a placebo
      and with 117 patients treated with of paracetamol 1000 mg and codeine 60 mg had
      73% (95%CI 56% to 81%) of patients with at least 50% pain relief, compared with
      57% (48% to 66%) in placebo controlled trials. Six trials in acute pain were
      omitted because of design issues, like the use of different pain measures or
      multiple dosing regimens. In each paracetamol 1000 mg and codeine 60 mg was shown
      to be better than placebo or comparators for at least one measure. CONCLUSIONS:
      Different designs of high quality trials can be used to support limited
      information used in meta-analysis without recourse to low quality trials that
      might be biased.

PMID- 11231886
TI  - Inhibition of carcinogen induced c-Ha-ras and c-fos proto-oncogenes expression by
      dietary curcumin.
AB  - BACKGROUND: We investigated the chemopreventive action of dietary curcumin on
      7,12-dimethylbenz(a)anthracene (DMBA)-initiated and 12,0-tetradecanoylphorbol-13
      acetate (TPA)-promoted skin tumor formation in Swiss albino mice. Curcumin, a
      yellow coloring matter isolated from roots of Curcuma longa Linn, is a phenolic
      compound possessing antioxidant, free radical scavenger, and antiinflammatory
      properties. It has been shown by previously reported work that TPA-induced skin
      tumors were inhibited by topical application of curcumin, and curcumin has been
      shown to inhibit a variety of biological activities of TPA. Topical application
      of curcumin was reported to inhibit TPA-induced c-fos, c-jun and c-myc gene
      expression in mouse skin. This paper reports the effects of orally administered
      curcumin, which was consumed as a dietary component at concentrations of 0.2 % or
      1 %, in ad libitum feeding. RESULTS: Animals in which tumors had been initiated
      with DMBA and promoted with TPA experienced significantly fewer tumors and less
      tumor volume if they ingested either 0.2% or 1% curcumin diets. Also, the dietary
      consumption of curcumin resulted in a significantly decreased expression of ras
      and fos proto-oncogenes in the tumorous skin, as measured by enhanced
      chemiluminesence Western blotting detection system (Amersham). CONCLUSIONS:
      Whereas earlier work demonstrated that topical application of curcumin to mouse
      skin inhibited TPA-induced expression of c-fos, c-jun and c-myc oncogenes, our
      results are the first to show that orally consumed curcumin significantly
      inhibited DMBA- and TPA-induced ras and fos gene expression in mouse skin.

PMID- 11231887
TI  - Differential expression of aquaporin 8 in human colonic epithelial cells and
      colorectal tumors.
AB  - BACKGROUND: The gene expression pattern in tumor cells differs from that in
      corresponding normal cells. In order to identify differentially expressed genes
      in colorectal tumors and normal colorectal epithelium, a differential display
      experiment was used to compare RNA expression in normal and tumor tissue samples.
      RESULTS: One gene fragment was expressed only in normal tissue and not, or to a
      much lesser extent, in the adenomas, carcinomas and cancer cell lines. The
      isolated gene fragment was identical to Aquaporin 8 (AQP8), a water channel
      protein. In situ hybridization demonstrated that AQP8 was expressed in the cells
      facing the lumen in the normal colonic epithelium. CONCLUSION: Our result
      suggests that the expression of AQP8 is a marker of normal proliferating colonic
      epithelial cells and suggest these cells to be involved in fluid transport in the
      colon.

PMID- 11231888
TI  - Maitotoxin-induced membrane blebbing and cell death in bovine aortic endothelial
      cells.
AB  - BACKGROUND: Maitotoxin, a potent cytolytic agent, causes an increase in cytosolic
      free Ca2+ concentration ([Ca2+]i) via activation of Ca2+-permeable, non-selective
      cation channels (CaNSC). Channel activation is followed by formation of large
      endogenous pores that allow ethidium and propidium-based vital dyes to enter the
      cell. Although activation of these cytolytic/oncotic pores, or COP, precedes
      release of lactate dehydrogenase, an indication of oncotic cell death, the
      relationship between CaNSC, COP, membrane lysis, and the associated changes in
      cell morphology has not been clearly defined. In the present study, the effect
      maitotoxin on [Ca2+]i, vital dye uptake, lactate dehydrogenase release, and
      membrane blebbing was examined in bovine aortic endothelial cells. RESULTS:
      Maitotoxin produced a concentration-dependent increase in [Ca2+]i followed by a
      biphasic uptake of ethidium. Comparison of ethidium (Mw 314 Da), YO-PRO-1 (Mw 375
      Da), and POPO-3 (Mw 715 Da) showed that the rate of dye uptake during the first
      phase was inversely proportional to molecular weight, whereas the second phase
      appeared to be all-or-nothing. The second phase of dye uptake correlated in time
      with the release of lactate dehydrogenase. Uptake of vital dyes at the single
      cell level, determined by time-lapse videomicroscopy, was also biphasic. The
      first phase was associated with formation of small membrane blebs, whereas the
      second phase was associated with dramatic bleb dilation. CONCLUSIONS: These
      results suggest that maitotoxin-induced Ca2+ influx in bovine aortic endothelial
      cells is followed by activation of COP. COP formation is associated with
      controlled membrane blebbing which ultimately gives rise to uncontrolled bleb
      dilation, lactate dehydrogenase release, and oncotic cell death.

PMID- 11231889
TI  - Why the fair innings argument is not persuasive.
AB  - The fair innings argument (FIA) is frequently put forward as a justification for
      denying elderly patients treatment when they are in competition with younger
      patients and resources are scarce. In this paper I will examine some arguments
      that are used to support the FIA. My conclusion will be that they do not stand up
      to scrutiny and therefore, the FIA should not be used to justify the denial of
      treatment to elderly patients, or to support rationing of health care by age.
      There are six issues arising out of the FIA which are to be addressed. First, the
      implication that there is such a thing as a fair share of life. Second, whether
      it makes sense to talk of a fair share of resources in the context of health care
      and the FIA. Third, that 'fairness' is usually only mentioned with regard to the
      length of a person's life, and not to any other aspect of it. Fourth, if it is
      sensible to discuss the merits of the FIA without taking account of the 'all
      other things being equal' argument. Fifth, the difference between what is unfair
      and what is unfortunate. Finally, that it is tragic if a young person dies, but
      only unfortunate if an elderly person does.

PMID- 11231890
TI  - Evolution of a metal-binding cluster in the NH(2)-terminal variable region of
      avian fast skeletal muscle troponin T: functional divergence on the basis of
      tolerance to structural drifting.
AB  - This study investigated the evolution of a transition metal ion-binding cluster
      ([H--X--X--X--H](n); Tx) in the alternatively spliced NH(2)-terminal variable
      region of avian pectoral muscle troponin T (TnT). Encoded by avian fast skeletal
      muscle TnT-specific P exons, Tx-like structures were expressed in the breast
      muscle TnT's of almost all birds examined. Their presence results in the
      developmentally up-regulated high molecular weight pectoral muscle TnT. Sequence
      analysis and metal affinity chromatography revealed that in Galliformes and
      Craciformes, the Tx structure evolved into multiple H--X--X--X--H pairs with a
      high-affinity metal-binding capacity. Turkey, chicken, quail, and curassow breast
      muscle TnT's contain nine, seven, four, and three consecutive or closely located
      metal-binding sites, respectively, in the NH(2)-terminal region. The metal
      binding affinity of the Tx element increased as the number of His pairs increased
      due to the duplication of P exons and the conversion of other exon sequences. The
      data show two related components of avian pectoral muscle TnT evolution: a
      larger, more acidic NH(2)-terminal segment and a cluster of transition metal
      binding sites, both of which may have functional significance for their selection
      value. The evolution of the Tx segment in the NH(2)-terminal variable region of
      avian pectoral muscle TnT demonstrates a functional divergence on the basis of
      tolerance to structural drifting.

PMID- 11231891
TI  - Phylogeny, genome evolution, and host specificity of single-stranded RNA
      bacteriophage (family Leviviridae).
AB  - Bacteriophage of the family Leviviridae have played an important role in
      molecular biology where representative species, such as Q beta and MS2, have been
      studied as model systems for replication, translation, and the role of secondary
      structure in gene regulation. Using nucleotide sequences from the coat and
      replicase genes we present the first statistical estimate of phylogeny for the
      family Leviviridae using maximum-likelihood and Bayesian estimation. Our analyses
      reveal that the coliphage species are a monophyletic group consisting of two
      clades representing the genera Levivirus and Allolevivirus. The Pseudomonas
      species PP7 diverged from its common ancestor with the coliphage prior to the
      ancient split between these genera and their subsequent diversification.
      Differences in genome size, gene composition, and gene expression are shown with
      a high probability to have changed along the lineage leading to the Allolevivirus
      through gene expansion. The change in genome size of the Allolevivirus ancestor
      may have catalyzed subsequent changes that led to their current genome
      organization and gene expression.

PMID- 11231892
TI  - A common structural motif in elongation factor Ts and ribosomal protein L7/12 may
      be involved in the interaction with elongation factor Tu.
AB  - Elongation factor (EF) Tu alternates between two interaction partners, EF-Ts and
      the ribosome, during its functional cycle. On the ribosome, the interaction
      involves, among others, ribosomal protein L7/12. Here we compare EF-Ts and L7/12
      with respect to the conservation of sequence and structure. There is significant
      conservation of functionally important residues in the N-terminal domain of EF-Ts
      and in the C-terminal domain of L7/12. The structure alignment based on the
      crystal structures of the two domains suggests a high degree of similarity
      between the alpha A--beta D--alpha B motif in L7/12 and the h1--turn--h2 motif in
      EF-Ts which defines a common structural motif. The motif is remarkably similar
      with respect to fold, bulkiness, and charge distribution of the solution surface,
      suggesting that it has a common function in binding EF-Tu.

PMID- 11231893
TI  - Structure and origin of a novel dimeric retroposon B1-diD.
AB  - Here we describe a new short retroposon family of rodents. Like the primate Alu
      element consisting of two similar monomers, it is dimeric, but the left and right
      monomers are different and descend from B1 and ID short retroposons,
      respectively. Such elements (B1-dID) were found in the genomes of Gliridae,
      Sciuridae, Castoridae, Caviidae, and Hystricidae. Nucleotide sequences of this
      retroposon can be assigned to several structural variants. Phylogenetic analysis
      of B1-dID and related sequences suggests a possible scenario of B1-dID evolution
      in the context of rodent evolution.

PMID- 11231894
TI  - A survey of the molecular evolutionary dynamics of twenty-five multigene families
      from four grass taxa.
AB  - We surveyed the molecular evolutionary characteristics of 25 plant gene families,
      with the goal of better understanding general processes in plant gene family
      evolution. The survey was based on 247 GenBank sequences representing four grass
      species (maize, rice, wheat, and barley). For each gene family, orthology and
      paralogy relationships were uncertain. Recognizing this uncertainty, we
      characterized the molecular evolution of each gene family in four ways. First, we
      calculated the ratio of nonsynonymous to synonymous substitutions (d(N)/d(S))
      both on branches of gene phylogenies and across codons. Our results indicated
      that the d(N)/d(S) ratio was statistically heterogeneous across branches in 17 of
      25 (68%) gene families. The vast majority of d(N)/d(S) estimates were <<1.0,
      suggestive of selective constraint on amino acid replacements, and no estimates
      were >1.0, either across phylogenetic lineages or across codons. Second, we
      tested separately for nonsynonymous and synonymous molecular clocks. Sixty-eight
      percent of gene families rejected a nonsynonymous molecular clock, and 52% of
      gene families rejected a synonymous molecular clock. Thus, most gene families in
      this study deviated from clock-like evolution at either synonymous or
      nonsynonymous sites. Third, we calculated the effective number of codons and the
      proportion of G+C synonymous sites for each sequence in each gene family. One or
      both quantities vary significantly within 18 of 25 gene families. Finally, we
      tested for gene conversion, and only six gene families provided evidence of gene
      conversion events. Altogether, evolution for these 25 gene families is marked by
      selective constraint that varies among gene family members, a lack of molecular
      clock at both synonymous and nonsynonymous sites, and substantial variation in
      codon usage.

PMID- 11231895
TI  - The geographic distribution of monoamine oxidase haplotypes supports a bottleneck
      during the dispersion of modern humans from Africa.
AB  - Every genetic locus mingles the information about the evolutionary history of the
      human species with the history of its own evolution. Therefore, to address the
      question of the origin of humans from a genetic point of view, evolutionary
      histories from many genetic loci have to be gathered and compared. We have
      studied two genes residing on the X chromosome encoding monoamine oxidases A and
      B (MAOA and MAOB). Both genes have been suggested to play a role in psychiatric
      and/or behavioral traits. To search for DNA variants of the MAO genes, the
      sequences of exonic and flanking intronic regions of these two genes were
      determined in a group of Swedish males. The sequence analysis revealed several
      novel polymorphisms in the MAO genes. Haplotypes containing high-frequency MAOA
      polymorphisms were constructed, and their frequencies were determined in
      additional samples from Caucasian, Asian, and African populations. We found two
      common haplotypes with similar frequencies in Caucasian and Asian populations.
      However, only one of them was also the most frequent haplotype in Africans, while
      the other haplotype was present in only one Kenyan male. This profound change in
      haplotype frequencies from Africans to non-Africans supports a possible
      bottleneck during the dispersion of modern humans from Africa.

PMID- 11231896
TI  - Correlation between Shine--Dalgarno sequence conservation and codon usage of
      bacterial genes.
AB  - In this study, we analyzed the correlation between codon usage bias and Shine-
      Dalgarno (SD) sequence conservation, using complete genome sequences of nine
      prokaryotes. For codon usage bias, we adopted the codon adaptation index (CAI),
      which is based on the codon usage preference of genes encoding ribosomal
      proteins, elongation factors, heat shock proteins, outer membrane proteins, and
      RNA polymerase subunit proteins. To compute SD sequence conservation, we used SD
      motif sequences predicted by Tompa and systematically aligned them with 5'UTR
      sequences. We found that there exists a clear correlation between the CAI values
      and SD sequence conservation in the genomes of Escherichia coli, Bacillus
      subtilis, Haemophilus influenzae, Archaeoglobus fulgidus, Methanobacterium
      thermoautotrophicum, and Methanococcus jannaschii, and no relationship is found
      in M. genitalium, M. pneumoniae, and Synechocystis. That is, genes with higher
      CAI values tend to have more conserved SD sequences than do genes with lower CAI
      values in these organisms. Some organisms, such as M. thermoautotrophicum, do not
      clearly show the correlation. The biological significance of these results is
      discussed in the context of the translation initiation process and translation
      efficiency.

PMID- 11231897
TI  - Low diversity and divergence in the fil1 gene family of Antirrhinum
      (Scrophulariaceae).
AB  - Detailed nucleotide diversity studies revealed that the fil1 gene of Antirrhinum,
      which has been reported to be single copy, is a member of a gene family composed
      of at least five genes. In four Antirrhinum majus populations with different
      mating systems and one A. graniticum population, diversity within populations is
      very low. Divergence among Antirrhinum species and between Antirrhinum and
      Digitalis is also low. For three of these genes we also obtained sequences from a
      more divergent member of the Scrophulariaceae, Verbascum nigrum. Compared with
      Antirrhinum, little divergence is again observed. These results, together with
      similar data obtained previously for five cycloidea genes, suggest either that
      these gene families (or the Antirrhinum genome) are unusually constrained or that
      there is a low rate of substitution in these lineages. Using a sample of 52
      genes, based on two measures of codon usage (ENC and GC3 content), we show that
      cyc and fil1 are among the least biased Antirrhinum genes, so that their low
      diversity is not due to extreme codon bias.

PMID- 11231898
TI  - Variable immune-driven natural selection in the attachment (G) glycoprotein of
      respiratory syncytial virus (RSV).
AB  - A maximum-likelihood analysis of selection pressures acting on the attachment (G)
      glycoprotein gene of respiratory syncytial virus (RSV) from humans (HRSV) and
      bovines (BRSV) is presented. Six positively selected sites were identified in
      both group A and group B of HRSV, although only one site was common between them,
      while no positively selected sites were detected in BRSV. All positively selected
      sites were located within the ectodomain of the G protein and showed some
      association with positions of immunoglobulin (Ig) epitopes and sites of O
      glycosylation. These results suggest that immune (antibody)-driven natural
      selection is an important determinant of RSV evolution and that this selection
      pressure differs among strains. The passage histories of RSV strains were also
      shown to affect the distribution of positively selected sites, particularly in
      HRSV B, and should be considered whenever retrospective analysis of adaptive
      evolution is undertaken.

PMID- 11231899
TI  - Olfactory receptor-gene clusters, genomic-inversion polymorphisms, and common
      chromosome rearrangements.
AB  - The olfactory receptor (OR)-gene superfamily is the largest in the mammalian
      genome. Several of the human OR genes appear in clusters with > or = 10 members
      located on almost all human chromosomes, and some chromosomes contain more than
      one cluster. We demonstrate, by experimental and in silico data, that unequal
      crossovers between two OR gene clusters in 8p are responsible for the formation
      of three recurrent chromosome macrorearrangements and a submicroscopic inversion
      polymorphism. The first two macrorearrangements are the inverted duplication of
      8p, inv dup(8p), which is associated with a distinct phenotype, and a
      supernumerary marker chromosome, +der(8)(8p23.1pter), which is also a recurrent
      rearrangement and is associated with minor anomalies. We demonstrate that it is
      the reciprocal of the inv dup(8p). The third macrorearrangment is a recurrent
      8p23 interstitial deletion associated with heart defect. Since inv dup(8p)s
      originate consistently in maternal meiosis, we investigated the maternal
      chromosomes 8 in eight mothers of subjects with inv dup(8p) and in the mother of
      one subject with +der(8), by means of probes included between the two 8p-OR gene
      clusters. All the mothers were heterozygous for an 8p submicroscopic inversion
      that was delimited by the 8p-OR gene clusters and was present, in heterozygous
      state, in 26% of a population of European descent. Thus, inversion heterozygosity
      may cause susceptibility to unequal recombination, leading to the formation of
      the inv dup(8p) or to its reciprocal product, the +der(8p). After the Yp
      inversion polymorphism, which is the preferential background for the PRKX/PRKY
      translocation in XX males and XY females, the OR-8p inversion is the second
      genomic polymorphism that confers susceptibility to the formation of common
      chromosome rearrangements. Accordingly, it may be possible to develop a profile
      of the individual risk of having progeny with chromosome rearrangements.

PMID- 11231900
TI  - Whole-genome screening in ankylosing spondylitis: evidence of non-MHC genetic
      susceptibility loci.
AB  - Ankylosing spondylitis (AS) is a common inflammatory arthritis predominantly
      affecting the axial skeleton. Susceptibility to the disease is thought to be
      oligogenic. To identify the genes involved, we have performed a genomewide scan
      in 185 families containing 255 affected sibling pairs. Two-point and multipoint
      nonparametric linkage analysis was performed. Regions were identified showing
      "suggestive" or stronger linkage with the disease on chromosomes 1p, 2q, 6p, 9q,
      10q, 16q, and 19q. The MHC locus was identified as encoding the greatest
      component of susceptibility, with an overall LOD score of 15.6. The strongest non
      MHC linkage lies on chromosome 16q (overall LOD score 4.7). These results
      strongly support the presence of non-MHC genetic-susceptibility factors in AS and
      point to their likely locations.

PMID- 11231901
TI  - Axonemal dynein intermediate-chain gene (DNAI1) mutations result in situs
      inversus and primary ciliary dyskinesia (Kartagener syndrome).
AB  - Kartagener syndrome (KS) is a trilogy of symptoms (nasal polyps, bronchiectasis,
      and situs inversus totalis) that is associated with ultrastructural anomalies of
      cilia of epithelial cells covering the upper and lower respiratory tracts and
      spermatozoa flagellae. The axonemal dynein intermediate-chain gene 1 (DNAI1),
      which has been demonstrated to be responsible for a case of primary ciliary
      dyskinesia (PCD) without situs inversus, was screened for mutation in a series of
      34 patients with KS. We identified compound heterozygous DNAI1 gene defects in
      three independent patients and in two of their siblings who presented with PCD
      and situs solitus (i.e., normal position of inner organs). Strikingly, these five
      patients share one mutant allele (splice defect), which is identical to one of
      the mutant DNAI1 alleles found in the patient with PCD, reported elsewhere.
      Finally, this study demonstrates a link between ciliary function and situs
      determination, since compound mutation heterozygosity in DNAI1 results in PCD
      with situs solitus or situs inversus (KS).

PMID- 11231902
TI  - A genetic factor for age-related cataract: identification and characterization of
      a novel galactokinase variant, "Osaka," in Asians.
AB  - Galactokinase (GALK) deficiency is an autosomal recessive disorder characterized
      by hypergalactosemia and cataract formation. Through mass screening of newborn
      infants, we identified a novel and prevalent GALK variant (designated here as the
      "Osaka" variant) associated with an A198V mutation in three infants with mild
      GALK deficiency. GALK activity and the amount of immunoreactive protein in the
      mutant were both 20% of normal construct in expression analysis. The K(m) values
      for galactose and ATP-Mg(2+) in erythrocytes with homozygous A198V were similar
      to those of the healthy adult control subjects. A population study for A198V
      revealed prevalences of 4.1% in Japanese and 2.8% in Koreans, lower incidence in
      Taiwanese and Chinese, no incidence in blacks and whites from the United States,
      and a significantly high frequency (7.8%; P < .023) in Japanese individuals with
      bilateral cataract. This variant probably originated in Japanese and Korean
      ancestors and is one of the genetic factors that causes cataract in elderly
      individuals.

PMID- 11231905
TI  - Antiatherogenic effects of thiazolidinediones?

PMID- 11231903
TI  - Cloning of dimethylglycine dehydrogenase and a new human inborn error of
      metabolism, dimethylglycine dehydrogenase deficiency.
AB  - Dimethylglycine dehydrogenase (DMGDH) (E.C. number 1.5.99.2) is a mitochondrial
      matrix enzyme involved in the metabolism of choline, converting dimethylglycine
      to sarcosine. Sarcosine is then transformed to glycine by sarcosine dehydrogenase
      (E.C. number 1.5.99.1). Both enzymes use flavin adenine dinucleotide and folate
      in their reaction mechanisms. We have identified a 38-year-old man who has a
      lifelong condition of fishlike body odor and chronic muscle fatigue, accompanied
      by elevated levels of the muscle form of creatine kinase in serum. Biochemical
      analysis of the patient's serum and urine, using (1)H-nuclear magnetic resonance
      NMR spectroscopy, revealed that his levels of dimethylglycine were much higher
      than control values. The cDNA and the genomic DNA for human DMGDH (hDMGDH) were
      then cloned, and a homozygous A-->G substitution (326 A-->G) was identified in
      both the cDNA and genomic DNA of the patient. This mutation changes a His to an
      Arg (H109R). Expression analysis of the mutant cDNA indicates that this mutation
      inactivates the enzyme. We therefore confirm that the patient described here
      represents the first reported case of a new inborn error of metabolism, DMGDH
      deficiency.

PMID- 11231906
TI  - Chemokines on the rise : mcp-1 and restenosis.

PMID- 11231907
TI  - Cytoskeletal effects of rho-like small guanine nucleotide-binding proteins in the
      vascular system.
AB  - Rho-like small GTPases, with their main representatives (Rho, Rac, and Cdc42),
      have been recognized in the past decade as key regulators of the F-actin
      cytoskeleton. Rho-like small GTPases are now known to play a major role in
      vascular processes caused by changes in the actin cytoskeleton, such as smooth
      muscle cell contraction, endothelial permeability, platelet activation, and
      leukocyte migration. Data are now accumulating regarding the involvement of Rho
      GTPases in vascular disorders associated with vascular remodeling, altered cell
      contractility, and cell migration. The unraveling of signal transduction pathways
      used by the Rho-like GTPases revealed many upstream regulators and downstream
      effector molecules, and their number is still growing. An important action of
      Rho, Rac, and Cdc42 is their ability to regulate the phosphorylation status of
      the myosin light chain, a major regulator of actin-myosin interaction. Present
      knowledge of the Rho-like small GTPases has resulted in the development of
      promising new strategies for the treatment of many vascular disorders, including
      hypertension, vasospasms, and vascular leakage.

PMID- 11231908
TI  - Cell lineages and tissue boundaries in cardiac arterial and venous poles:
      developmental patterns, animal models, and implications for congenital vascular
      diseases.
AB  - Multiple cell populations with different embryological histories are involved in
      the morphogenesis of the cardiac arterial and venous poles as well as in the
      correct alignment and connection of the developing vessels with the cardiac
      chambers. Formation of the aorta and the pulmonary trunk is a complicated process
      orchestrated via a specific sequence of highly integrated spatiotemporal events
      of cell proliferation, migration, differentiation, and apoptosis. The peculiar
      susceptibility of this intricate cell network to be altered explains the
      frequency of congenital cardiovascular diseases of the arterial and venous poles.
      We review this topic from the "vascular point of view," putting major emphasis on
      (1) the existence of different cell lineages from which smooth muscle cells of
      the aorticopulmonary trunk can be derived, (2) the establishment of cell/tissue
      boundaries in the cardiovascular connecting regions, and (3) the animal models
      that can mimic human congenital defects of the arterial and venous poles of the
      heart.

PMID- 11231909
TI  - Reactive oxygen species regulate heat-shock protein 70 via the JAK/STAT pathway.
AB  - Reactive oxygen species (ROS) such as hydrogen peroxide (H(2)O(2)) activate
      intracellular signal transduction pathways implicated in the pathogenesis of
      cardiovascular disease. H(2)O(2) is a mitogen for rat vascular smooth muscle
      cells (VSMCs), and protein tyrosine phosphorylation is a critical event in VSMC
      mitogenesis. Therefore, we investigated whether the mitogenic effects of
      H(2)O(2), such as stimulation of extracellular signal-regulated kinase (ERK)2,
      are mediated via activation of cytoplasmic Janus tyrosine kinases (JAKs). JAK2
      was activated rapidly in VSMCs treated with H(2)O(2), and signal transducers and
      activators of transcription (STAT) STAT1 and STAT3 were tyrosine-phosphorylated
      and translocated to the nucleus in a JAK2-dependent manner. Inhibition of JAK2
      activity with AG-490 partially inhibited H(2)O(2)-induced ERK2 activity,
      suggesting that JAK2 is upstream of the Ras/Raf/mitogen-activated protein kinase
      ERK/ERK mitogenic pathway. Because heat-shock proteins (HSPs) can protect cells
      from ROS, we investigated the effect of H(2)O(2) on HSP expression. H(2)O(2)
      stimulated HSP70 expression in a time-dependent manner, and AG-490 abolished
      H(2)O(2)-induced HSP70 expression. H(2)O(2) activated the HSP70 promoter via
      enhanced binding of STATs to cognate binding sites in the promoter. Regulation of
      chaperones such as HSP70 via activation of the JAK/STAT pathway suggests that in
      addition to its growth-promoting effects, this pathway may help VSMCs adapt to
      oxidative stress.

PMID- 11231910
TI  - Elevated circulating levels of monocyte chemoattractant protein-1 in patients
      with restenosis after coronary angioplasty.
AB  - Inflammation plays a pathogenic role in the development of restenosis after
      percutaneous transluminal coronary angioplasty (PTCA). Monocyte chemoattractant
      protein-1 (MCP-1) is a potent chemoattractant of monocytes; however, its role in
      the pathophysiology of restenosis is still unclear. We set out to investigate the
      role of MCP-1 in restenosis after PTCA. In addition, we tested the hypothesis
      that MCP-1 exerts its effect, at least in part, by inducing O(2)(-) generation in
      circulating monocytes. Plasma levels of MCP-1 were measured before and 1, 5, 15,
      and 180 days after PTCA in 50 patients (30 males and 20 females, aged 62+/-5
      years) who underwent PTCA and who had repeated angiograms at 6-month follow-up.
      Restenosis occurred in 14 (28%) patients. The MCP-1 level was no different at
      baseline between patients with or without restenosis. However, after the
      procedure, restenotic patients, compared with nonrestenotic patients, had
      statistically significant (P<0.0001) elevated levels of MCP-1. In contrast,
      plasma levels of other chemokines, such as RANTES and interleukin-8, did not
      differ between the 2 groups after PTCA. Higher MCP-1 throughout the study was
      correlated with restenosis. Moreover, increased MCP-1 was significantly
      correlated with increased monocyte activity, as reflected by enhanced O(2)(-)
      generation. Finally, multivariate regression analysis showed that the MCP-1
      plasma level measured 15 days after PTCA was the only statistically significant
      independent predictor of restenosis (beta=0.688, P<0.0001). This study suggests
      that MCP-1 production and macrophage accumulation in the balloon-injured vessel
      may play a pivotal role in restenosis after PTCA. MCP-1 may induce luminal
      renarrowing, at least in part, by inducing O(2)(-) release in monocytes. Further
      understanding of the mechanism(s) by which MCP-1 is produced and acts after
      arterial injury may provide insight into therapies to limit the progression of
      atherosclerosis and restenosis after balloon angioplasty.

PMID- 11231911
TI  - Insulin-like growth factor binding protein-4 protease produced by smooth muscle
      cells increases in the coronary artery after angioplasty.
AB  - Insulin-like growth factor (IGF)-I stimulates vascular smooth muscle cell (VSMC)
      migration and proliferation, which are fundamental to neointimal hyperplasia in
      postangioplasty restenosis. IGF-I action is modulated by several high-affinity
      IGF binding proteins (IGFBPs). IGFBP-4 is the predominant IGFBP produced by VSMCs
      and is a potent inhibitor of IGF-I action. However, specific IGFBP-4 proteases
      can cleave IGFBP-4 and liberate active IGF-I. In this study, we document IGFBP-4
      protease produced by human and porcine coronary artery VSMCs in culture as
      pregnancy-associated plasma protein-A (PAPP-A). This was shown by a distinctive
      IGFBP-4 cleavage pattern, specific inhibition of IGFBP-4 protease activity with
      PAPP-A polyclonal antibodies, and immunorecognition of PAPP-A by monoclonal
      antibodies. Furthermore, we found a 2-fold increase in IGFBP-4 protease activity
      in injured porcine VSMC cultures in vitro (P<0.05). We also evaluated IGFBP-4
      protease/PAPP-A expression in vivo after coronary artery balloon injury. Twenty
      five immature female pigs underwent coronary overstretch balloon injury, and
      vessels were examined at defined time points after the procedure. Abundant PAPP-A
      expression was observed in the cytoplasm of medial and neointimal cells 7, 14,
      and 28 days after angioplasty (P<0.01 vs control). The highest PAPP-A labeling
      indices were located in the neointima (36.1+/-2.1%) and the media (31.7+/-1.2%)
      28 days after injury. Western blot analysis confirmed increased PAPP-A in injured
      vessels. PAPP-A, a regulator of IGF-I bioavailability through proteolysis of
      IGFBP-4, is thus expressed by VSMCs in vitro and in restenotic lesions in vivo.
      These results suggest a possible role for PAPP-A in neointimal hyperplasia.

PMID- 11231912
TI  - Role of Sp1 in the induction of p27 gene expression in vascular smooth muscle
      cells in vitro and after balloon angioplasty.
AB  - -The abnormal proliferation of vascular smooth muscle cells (VSMCs) plays an
      important role in atherosclerosis and restenosis. Although several studies have
      implicated the growth inhibitory protein p27(Kip1) (p27) in the control of
      myocyte growth and hypertrophy, little is known about the molecular mechanisms
      that regulate p27 expression in the cardiovascular system. In the present study,
      we demonstrate the interaction of the transcription factor Sp1 with 2 GC-rich
      sequences within the p27 promoter in cultured VSMCs. Importantly, point mutations
      that disrupted Sp1 binding markedly reduced p27 promoter activity, demonstrating
      that Sp1 is required for efficient p27 gene transcription in cultured VSMCs.
      Because p27 expression is upregulated after balloon angioplasty, we investigated
      Sp1 expression and activity in control and balloon-injured rat carotid arteries
      to assess the role of Sp1 as a physiological regulator of p27 expression.
      Although immunohistochemical analysis disclosed Sp1 protein expression in both
      control and balloon-injured arteries, a high level of Sp1 DNA-binding activity
      was found only in response to balloon angioplasty. Collectively, these results
      demonstrate that Sp1 is essential for maximum p27 promoter activity in VSMCs and
      suggest that posttranslational induction of Sp1 DNA-binding activity contributes
      to the induction of p27 expression and VSMC growth arrest at late time points
      after balloon angioplasty.

PMID- 11231913
TI  - Overexpression of inducible heat shock protein 70 in Cos-1 cells fails to protect
      from cytotoxicity of oxidized ldls.
AB  - Oxidized low density lipoproteins (OxLDLs) are believed to play a central role in
      atherogenesis and to possess a wide variety of biological properties; among them,
      OxLDLs are cytotoxic to cultured vascular cells in that they induce necrosis and
      apoptosis. Moreover, OxLDLs are known to induce the expression of heat shock
      protein 70 (Hsp70), a protein that protects cells from several cytotoxic stimuli.
      To determine whether Hsp70 can protect cells against OxLDL-induced cytotoxicity,
      COS-1 cells were transfected with a construct containing human Hsp70. A number of
      cell lines permanently expressing Hsp70 were obtained, 1 of which (cos-Hsp70/10,
      with high Hsp70 expression) was selected for further studies. Hsp70
      overexpression protected cells from toxic stimuli, such as H(2)O(2), UV
      irradiation, and heat shock, suggesting that the overexpressed protein was
      functional. When incubated with OxLDLs, however, the clone overexpressing Hsp70
      showed a significant decrease in viability, as determined by the [(3)H]adenine
      release assay (319.8+/-3.16% of control for transfected cells versus 217.6+/
      6.08% for control cells exposed to 100 microgram protein/mL of OxLDL), 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (12.5+/-0.9% versus
      28.9+/-1.99% of control, respectively), and LDH release (48.4+/-0.04% versus
      15.2+/-0.06% of control cells). The increased expression of BAX and the decreased
      expression of Bcl-2 (a proapoptotic and an antiapoptotic protein, respectively)
      in cos-Hsp70/10 cells and in control cells on incubation with OxLDLs suggested
      that overexpression of Hsp70 did not confer protection against apoptosis induced
      by OxLDLs. The analysis of nucleosome content and the nuclear staining with
      Hoechst 33258 confirmed this finding. These data suggest that overexpression of
      Hsp70 not only fails to protect COS-1 cells against OxLDL-induced apoptosis but
      rather confers a higher sensitivity to the cytotoxic action of these
      lipoproteins. Thus, the Hsp70 response, although induced by OxLDLs, cannot
      protect cells from lipoprotein toxicity.

PMID- 11231914
TI  - Regional differentiation of desmin, connexin43, and connexin45 expression
      patterns in rat aortic smooth muscle.
AB  - The gap-junctional protein, connexin43, is differentially expressed in vascular
      smooth muscle cells (SMCs) according to phenotype. Previous studies suggest that
      desmin-negative SMCs are characterized by high levels of connexin43, whereas
      desmin-positive SMCs (of a more contractile phenotype) typically have low
      connexin43 levels. In this study, we examine systematically the inverse
      relationship between connexin43 and desmin in SMCs of defined regions of the rat
      aortic media and determine whether additional connexin isotypes are expressed and
      contribute to this relationship. Immunoconfocal microscopy demonstrated that (1)
      the inverse relationship between connexin43 and desmin expression holds true for
      the media of sequential aortic zones, with 1 exception, the ascending aorta, and
      (2) an additional vascular connexin, connexin45, is expressed by aortic SMCs.
      Examination of connexin43, connexin45, and desmin expression in sequential aortic
      zones reveals 3 SMC subpopulations. The first, predominating in the aortic arch
      and thoracic aorta, is desmin negative and contains high connexin43 levels; the
      second, predominating in the abdominal aorta and iliac artery, is desmin positive
      and contains low connexin43 levels; and the third, which is restricted to the
      ascending aorta, is desmin positive and expresses high connexin43 levels.
      Connexin45 levels are high in the ascending aorta but low in the other aortic
      segments. In para-aortic veins, a fourth SMC subpopulation appears, one that is
      desmin positive and contains connexin45 but not connexin43. These results
      demonstrate that a diversity of connexin expression patterns characterizes
      distinctive subpopulations of medial SMCs in situ with a potential to contribute
      to regional differentiation of vascular function.

PMID- 11231915
TI  - Troglitazone inhibits formation of early atherosclerotic lesions in diabetic and
      nondiabetic low density lipoprotein receptor-deficient mice.
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a ligand
      activated nuclear receptor expressed in all of the major cell types found in
      atherosclerotic lesions: monocytes/macrophages, endothelial cells, and smooth
      muscle cells. In vitro, PPARgamma ligands inhibit cell proliferation and
      migration, 2 processes critical for vascular lesion formation. In contrast to
      these putative antiatherogenic activities, PPARgamma has been shown in vitro to
      upregulate the CD36 scavenger receptor, which could promote foam cell formation.
      Thus, it is unclear what impact PPARgamma activation will have on the development
      and progression of atherosclerosis. This issue is important because
      thiazolidinediones, which are ligands for PPARgamma, have recently been approved
      for the treatment of type 2 diabetes, a state of accelerated atherosclerosis. We
      report herein that the PPARgamma ligand, troglitazone, inhibited lesion formation
      in male low density lipoprotein receptor-deficient mice fed either a high-fat
      diet, which also induces type 2 diabetes, or a high-fructose diet. Troglitazone
      decreased the accumulation of macrophages in intimal xanthomas, consistent with
      our in vitro observation that troglitazone and another thiazolidinedione,
      rosiglitazone, inhibited monocyte chemoattractant protein-1-directed
      transendothelial migration of monocytes. Although troglitazone had some
      beneficial effects on metabolic risk factors (in particular, a reduction of
      insulin levels in the diabetic model), none of the systemic cardiovascular risk
      factors was consistently improved in either model. These observations suggest
      that the inhibition of early atherosclerotic lesion formation by troglitazone may
      result, at least in part, from direct effects of PPARgamma activation in the
      artery wall.

PMID- 11231916
TI  - Troglitazone inhibits atherosclerosis in apolipoprotein E-knockout mice:
      pleiotropic effects on CD36 expression and HDL.
AB  - Atherosclerotic coronary heart disease is a common complication of the insulin
      resistance syndrome that can occur with or without diabetes mellitus.
      Thiazolidinediones (TZDs), which are insulin-sensitizing antidiabetic agents, can
      modulate the development of atherosclerosis not only by changing the systemic
      metabolic conditions associated with insulin resistance but also by exerting
      direct effects on vascular wall cells that express peroxisome proliferator
      activated receptor-gamma (PPAR-gamma), a nuclear receptor for TZDs. Here we show
      that troglitazone, a TZD, significantly inhibited fatty streak lesion formation
      in apolipoprotein E-knockout mice fed a high-fat diet (en face aortic surface
      lesion areas were 6.9+/-2.5% vs 12.7+/-4.7%, P<0.05; cross-sectional lesion areas
      were 191 974+/-102 911 micrometer(2) vs 351 738+/-175 597 micrometer(2), P<0.05;
      n=10). Troglitazone attenuated hyperinsulinemic hyperglycemia and increased high
      density lipoprotein cholesterol levels. In the aorta, troglitazone markedly
      increased the mRNA levels of CD36, a scavenger receptor for oxidized low density
      lipoprotein, presumably by upregulating its expression, at least in part, in the
      macrophage foam cells. These results indicate that troglitazone potently inhibits
      fatty streak lesion formation by modulating both metabolic extracellular
      environments and arterial wall cell functions.

PMID- 11231917
TI  - Localization of human ATP-binding cassette transporter 1 (ABC1) in normal and
      atherosclerotic tissues.
AB  - The present study examines the expression of ATP-binding cassette transporter 1
      (ABC1) mRNA in normal and atherosclerotic tissues by using in situ hybridization
      in an effort to better understand the function of this cholesterol transport
      protein. Samples of normal baboon tissues as well as human normal and
      atherosclerotic aortas were hybridized with (35)S-labeled ABC1 sense and
      antisense riboprobes. Widespread expression of ABC1 was observed generally in
      tissues containing inflammatory cells and lymphocytes. Other noninflammatory
      cells that were also sites of ABC1 synthesis included the ductal cells of the
      kidney medulla, Leydig cells in the testis, and glial cells in the baboon
      cerebellum. Although normal veins and arteries did not express ABC1 mRNA, it was
      found to be upregulated in the setting of atherosclerosis, where widespread
      expression was found in macrophages within atherosclerotic lesions. These results
      are consistent with the proposed role of ABC1 in cholesterol transport in
      inflammatory cells. The specific upregulation of ABC1 mRNA in the setting of
      atherosclerosis probably reflects the response of leukocytes to cholesterol
      loading. However, the presence of ABC1 in ductal cells of the kidney medulla and
      in the small intestine suggest a more general role for this protein in
      cholesterol transport in other cell types.

PMID- 11231918
TI  - Retention of oxidized LDL by extracellular matrix proteoglycans leads to its
      uptake by macrophages: an alternative approach to study lipoproteins cellular
      uptake.
AB  - Interaction between arterial macrophages and oxidized LDL (Ox-LDL) leads to foam
      cell formation, a critical step during early atherogenesis. Until now, cellular
      uptake of lipoproteins was studied through incubation of the media-soluble
      lipoprotein with cultured macrophages. However, as lipoproteins in the arterial
      wall are bound to subendothelial matrix, we questioned whether the retention
      (binding) of Ox-LDL to a macrophage-derived extracellular matrix (ECM) could lead
      to enhanced uptake by macrophages. The uptake of ECM-bound Ox-LDL by activated
      macrophages (by phorbol myristate acetate) was lipoprotein dose dependent, time
      dependent and higher (by 1.5-fold) than the uptake of ECM-bound native LDL.
      Preincubation of the ECM with lipoprotein lipase before the addition of Ox-LDL
      was essential for the uptake of ECM-bound Ox-LDL by the macrophages. After
      radiolabeling of the ECM glycosaminoglycans (GAGs), we found that ECM-bound Ox
      LDL is taken up by the macrophages together with the ECM-GAG. Finally, these
      results were further confirmed through the use of ECM obtained from mouse
      peritoneal macrophages (MPMs), derived from atherosclerotic, apoE-deficient mice.
      In 24-week-old mice with developed atherosclerosis, the GAG content of their MPM
      derived ECM increased by 52%, the ability of their MPM-derived ECM to bind Ox-LDL
      increased by 57%, and macrophage uptake of Ox-LDL that was retained by the MPM
      derived ECM increased by 86%. In conclusion, the present study demonstrated that
      ECM-bound Ox-LDL is taken up by activated macrophages. This may represent a
      physiopathological phenomenon that leads to cholesterol and oxysterol
      accumulation in arterial macrophages, the hallmark of early atherosclerosis.

PMID- 11231919
TI  - Effect of probucol in lecithin-cholesterol acyltransferase-deficient mice:
      inhibition of 2 independent cellular cholesterol-releasing pathways in vivo.
AB  - Cellular cholesterol release takes place by at least 2 distinct mechanisms: the
      lecithin-cholesterol acyltransferase (LCAT)-driven net efflux by cholesterol
      diffusion and the generation of high density lipoprotein (HDL) with cellular
      cholesterol and phospholipid on the cell-apolipoprotein interaction. Therefore,
      LCAT deficiency impairs the former pathway, and the latter can be inhibited by
      probucol, which interferes with the apolipoprotein-cell interaction. Hence,
      probucol was given to the LCAT-deficient mice in the attempt to suppress both of
      these pathways. The mice were fed low (0.2%) and high (1.2%) cholesterol diets
      containing 0.5% probucol for 2 weeks. LCAT deficiency and probucol markedly
      decreased plasma HDL, and the effects were synergistic. Tissue cholesterol
      content was lower in the adrenal glands and ovaries in the LCAT-deficient mice
      and in the probucol-treated mice, suggesting that HDL is a main cholesterol
      provider for these organs. It was also moderately decreased in the spleen of the
      low cholesterol-fed female mice and in the thyroid gland of the low cholesterol
      fed male mice. On the other hand, the esterified cholesterol content in the liver
      was substantially increased by the probucol treatment with a high cholesterol
      diet in the LCAT-deficient mice but not in the wild-type mice. Among the groups,
      there was no significant difference in the tissue cholesterol levels in other
      organs, such as the liver, spleen, thymus, brain, erythrocytes, thyroid gland,
      testis, and aorta, resulting from either LCAT deficiency or probucol. Thus, the
      apolipoprotein-mediated mechanism plays a significant role in the export of
      cellular cholesterol in the liver, indicating that the liver is a major site of
      the HDL assembly. Otherwise, tissue cholesterol homeostasis can largely be
      maintained in mice even when the assembly of new HDL is inhibited by probucol in
      the absence of LCAT. Nonspecific diffusion of cholesterol perhaps adequately
      maintains the homeostasis in the experimental condition.

PMID- 11231920
TI  - Lack of triglyceride-lowering properties of fish oil in apolipoprotein e
      deficient mice.
AB  - Fish oil is a potent triglyceride (TG)-lowering agent in humans. The goal of the
      present study was to assess the contribution of decreased triglyceride synthesis
      and of apoE in mediation of the triglyceride-lowering effect of fish oil. To this
      end, apoE-deficient mice and wild-type control mice were supplemented with either
      coconut oil, sunflower oil, or fish oil (20% wt/wt) for 2 weeks. Compared with
      coconut oil and sunflower oil, fish oil reduced the concentrations of cholesterol
      and triglycerides in the wild-type mice, whereas it had no effect on cholesterol
      concentration and it had a triglyceride-raising effect in apoE-deficient mice.
      The latter was due to increased triglyceride concentrations in the d<1.019 g/mL
      plasma density fraction. In apoE-deficient mice, but not in wild-type mice, the
      postprandial triglyceride area under the curve was higher after an intragastric
      load of fish oil than after a sunflower oil load. These data indicate an
      impairment of triglyceride metabolism in the fish oil-fed apoE-deficient mice.
      Compared with coconut oil and sunflower oil, fish oil lowered triglyceride
      production rates measured with the Triton method in both wild-type (P<0.0001) and
      apoE-deficient mice (P<0.0001). Similarly, in vitro lipoprotein lipase-mediated
      lipolysis of VLDL was lowered in the fish oil-fed wild-type and apoE-deficient
      mice, suggesting an alteration in VLDL lipolysis independent of the mice
      genotype. In conclusion, fish oil does not decrease triglyceride concentrations
      in apoE-deficient mice despite reducing triglyceride production rates, suggesting
      that decreased triglyceride synthesis is not sufficient to lower triglyceride
      concentrations in mice. ApoE appears to be necessary for fish oil to lower plasma
      triglyceride concentrations, indicating a critical role of apoE in this process.

PMID- 11231921
TI  - Accumulation of triglyceride-rich lipoprotein in subjects with abdominal obesity:
      the biguanides and the prevention of the risk of obesity (BIGPRO) 1 study.
AB  - The present study represents a new insight into the Biguanides and the Prevention
      of the Risk of Obesity (BIGPRO) 1 study population at inclusion. This population,
      selected basically on the basis of a high waist-to-hip ratio (>/=0.95 for men and
      >/=0.80 for women), is supposed to represent a group of patients with insulin
      resistance. The present study was undergone to establish whether apolipoprotein C
      III (apoC-III) and apolipoprotein E (apoE) associated with apo B (apoC-III LpB
      and apoE LpB, respectively), considered to be markers of remnant accumulation,
      play a role in the hypertriglyceridemia associated with insulin resistance and
      whether they are related to other biological abnormalities frequently observed in
      this syndrome. In this population, the concentration of the markers of remnant
      accumulation increases with triglyceride levels. Therefore, correlation studies
      were realized to assess the relative effect of insulin and the markers of remnant
      accumulation on triglyceride plasma level. As a first attempt, a simple
      correlation analysis revealed that insulin is positively related to the markers
      of remnant accumulation only in hypertriglyceridemic patients (triglycerides
      >/=1.7 mmol/L). To assess the independent contribution of these markers, insulin,
      and other parameters related to the plasma triglyceride concentration, a stepwise
      multiple regression analysis was run. Results revealed that insulin and the
      markers of remnant accumulation (specifically, apoE LpB) are independent
      contributors to the plasma triglyceride concentration. Markers of the endothelial
      damage, plasminogen activator inhibitor-1, tissue plasminogen activator, and von
      Willebrand factor, which are often increased in the case of insulin resistance,
      were tested for their correlation with the markers of remnant accumulation.
      Plasminogen activator inhibitor-1 is positively correlated with these markers
      only in hypertriglyceridemic male subjects. It is concluded that increased
      insulin levels found in insulin resistance syndrome are associated with an
      increased production of triglyceride-rich lipoproteins enriched in apoC-III and
      apoE. The accumulation of these remnants and/or their abnormal composition in
      apoC-III and apoE could be an explanation for the development of
      hypertriglyceridemia in this syndrome.

PMID- 11231923
TI  - Natural history and topographic pattern of progression of coronary calcification
      in symptomatic patients: An electron-beam CT study.
AB  - Electron-beam CT may assess the progression of coronary atherosclerosis by
      visualizing changes in calcification. The present investigation analyzes (1) the
      rate of progression of calcification in symptomatic patients, (2) the topographic
      pattern, and (3) the influence of baseline plaque burden and risk factors.
      Progression of calcification during a mean (median) interval of 18 (15) months
      was measured in 102 symptomatic outpatients (aged 59+/-9 years, 80% male) with
      calcification. In 4 patient groups with a baseline total score (Agatston
      criteria) of 1 to 30, >30 to 100, >100 to 400, and >400, the median was 3.1,
      26.1, 58.9, and 109.7, respectively, for absolute annual progression of the score
      (P<0.05) and 57%, 49%, 32%, and 15%, respectively, for relative progression
      (P<0.05). On the coronary segmental level, changes were largely restricted to
      typical predilection sites of coronary atherosclerosis. The presence of
      angiographically defined coronary narrowing influenced absolute, but not
      relative, progression. Of the risk factors, only low density lipoprotein
      cholesterol levels showed a trend, although not significant, for predicting
      progression. These data indicate that baseline plaque burden determines the rate
      of progression of calcification. This appears to be a coronary systemic process,
      reflecting the natural history of coronary atherosclerosis.

PMID- 11231922
TI  - Paraoxonase1-192 polymorphism modulates the nonfatal myocardial infarction risk
      associated with decreased HDLs.
AB  - Serum paraoxonase1 (PON1), a high density lipoprotein (HDL)-linked enzyme,
      appears to have a role in the protection of low density lipoproteins from
      oxidative stress. PON1 enzyme activity for paraoxon as a substrate is modulated,
      along with others at the PON1 locus, by the PON1-192 polymorphism, which contains
      low paraoxon-activity and high paraoxon-activity alleles (Q and R, respectively).
      The association of PON1 with HDL suggests that impaired serum concentrations of
      the lipoprotein could have consequences for the susceptibility to oxidative
      stress. Because PON1-192 polymorphism strongly influences PON1 activity toward
      paraoxon, we tested the hypothesis that this polymorphism may modulate the
      myocardial infarction (MI) risk associated with low HDL cholesterol
      concentrations. Two hundred eighty consecutive MI patients and 396 control
      subjects were studied. When considered as a whole, PON1-192 genetic polymorphism
      was not associated with higher MI risk. In the entire population, decreased HDL
      cholesterol concentration (<0.90 mmol/L in men and <1.11 mmol/L in women)
      conferred an MI risk of 2.56 (P=0.0001) compared with normal HDL levels. The risk
      increased to 4.51 (P<0.0001) in QQ homozygous HDL-deficient subjects relative to
      QQ homozygotes with normal HDL levels, decreased to 1.83 (P=0.1046) in QR
      heterozygote HDL-deficient subjects, and also decreased (to 1.41, P=0.6243) in RR
      homozygote HDL-deficient individuals compared with RR carriers with normal HDL
      cholesterol concentration. The effect of PON1-192 genotypes on the association of
      low HDL cholesterol levels and MI was related to gene dosage. A significantly
      decreased enzyme activity was found in HDL-deficient MI patients compared with
      HDL-deficient control subjects (median 208 U/L [interquartile range 136 to 298
      U/L] versus median 235 U/L [interquartile range 163 to 350 U/L], respectively;
      P=0.025]. QQ homozygous MI patients showed the greatest difference of PON1
      activity levels between normal and HDL-deficiency state groups (14.9%, P=0.002).
      Our observations raise the question of whether the decrease in PON1 activity and
      the MI risk associated with HDL deficiency are more evident in the low paraoxon
      activity QQ genotype. It can be argued that the low paraoxon-activity QQ
      genotype, which may be adequate to prevent lipid peroxidation in normolipidemic
      subjects, may be insufficient when an HDL-deficiency state and low PON1 activity
      reflecting oxidative stress coexist. The risk of nonfatal MI is increased in HDL
      deficiency states, principally among subjects carrying the low paraoxon-activity
      QQ genotype.

PMID- 11231924
TI  - Current infection with Helicobacter pylori, but not seropositivity to Chlamydia
      pneumoniae or cytomegalovirus, is associated with an atherogenic, modified lipid
      profile.
AB  - Infectious agents may be involved in atherothrombogenesis. The potential
      pathogenic pathway, however, remains unclear. We investigated the association
      between various infectious agents and lipoproteins known to have an atherogenic
      effect. We recruited 470 healthy blood donors and 238 patients with
      angiographically proven coronary heart disease (CHD), aged 40 to 68 years.
      Seropositivity to Chlamydia pneumoniae (CP), chlamydial lipopolysaccharide, and
      cytomegalovirus (CMV) was determined; infection with Helicobacter pylori (HP) was
      assessed by using the [(13)C]urea breath test. In all subjects, total
      cholesterol, high density lipoprotein (HDL) cholesterol, lipoprotein(a), and
      various apolipoproteins (apos) were determined. In unadjusted analysis, mean HDL
      cholesterol concentration was significantly decreased in HP-positive healthy
      subjects (1.36 vs 1.44 mmol/L, P=0.006) compared with HP-negative subjects. The
      HDL cholesterol to total cholesterol ratio was significantly decreased in HP
      positive (0.259 vs 0.276, P=0.01) and CP-seropositive (0.266 vs 0.280, P=0.04)
      healthy subjects compared with (sero)negatives. Mean apoAI levels were
      significantly lower in HP-positive healthy subjects (1.46 vs 1.51 g/L, P=0.03)
      and in CMV-positive healthy subjects (1.47 vs 1.52 g/L, P=0.01) compared with
      (sero)negative subjects. After multivariable adjustment by means of linear
      regression analysis, only the association between HP infection and decreased HDL
      cholesterol (P=0.002), decreased HDL cholesterol to total cholesterol ratio
      (P:=0.005), decreased apoAI (P=0.02), and increased apoB (P=0.02) persisted and
      remained significant. There was no independent association between other
      lipoproteins and serological markers of CP or CMV infection. Current infection
      with HP, but not seropositivity to CP or CMV, was associated with an atherogenic,
      modified lipid profile. These lipid alterations could explain, at least in part,
      the reported weak association between chronic HP infection and atherosclerotic
      diseases.

PMID- 11231925
TI  - Impact of apolipoprotein(a) on in vitro angiogenesis.
AB  - Angiostatin, which consists of the kringle I-IV domains of plasminogen and which
      is secreted into urine, is an efficient inhibitor of angiogenesis and tumor
      growth. Because N-terminal apolipoprotein(a) [apo(a)] fragments, which also
      contain several types of kringle IV domains, are found in urine as well, we
      evaluated the potential angiostatic properties of these urinary apo(a) fragments
      and of a recombinant form of apo(a) [r-apo(a)]. We used human microvascular
      endothelial cell (hMVEC)-based in vitro assays of tube formation in 3-dimensional
      fibrin matrixes. Purified urinary apo(a) fragments or r-apo(a) inhibited the
      basic fibroblast growth factor/tumor necrosis factor-alpha-induced formation of
      capillary-like structures. At concentrations varying from 0.2 to 10 microgram/mL,
      urinary apo(a) fragments inhibited tube formation by as much as 70%, whereas
      there was complete inhibition by r-apo(a). The highest concentrations of both
      inhibitors also reduced urokinase plasminogen activator production of basic
      fibroblast growth factor-induced hMVEC proliferation. The inhibitors had no
      effect on plasminogen activator inhibitor-1 expression. If our in vitro model for
      angiogenesis is valid for the in vivo situation as well, our data point toward
      the possibility that apo(a) may also be physiologically operative in modulating
      angiogenesis, as the concentration of free apo(a) found in humans exceeds that
      tested herein.

PMID- 11231926
TI  - Alcohol enhances oxysterol-induced apoptosis in human endothelial cells by a
      calcium-dependent mechanism.
AB  - Controversy exists about the net effect of alcohol on atherogenesis. A protective
      effect is assumed, especially from the tannins and phenolic compounds in red
      wine, owing to their inhibition of low density lipoprotein (LDL) oxidation.
      However, increased atherogenesis occurs in subjects with moderate to heavy
      drinking habits. The purpose of this study was to investigate the influence of
      alcohol in combination with oxysterols on the endothelium. Cultured human
      arterial endothelial cells (HAECs) served as an in vitro model to test the
      cellular effects of various oxysterols. Oxysterols (7beta-hydroxycholesterol, 7
      ketocholesterol, and cholesterol-5,6-epoxides), which are assumed to be the most
      toxic constituents of oxidized LDL, induced apoptosis in HAECs through calcium
      mobilization followed by activation of caspase-3. Ethanol, methanol, isopropanol,
      tert-butanol, and red wine all potentiated oxysterol-induced cell death up to 5
      fold, paralleled by further induction of caspase-3. The alcohol effect occurred
      in a dose-dependent manner and reached a plateau at 0.05% concentration. Alcohol
      itself did not affect endothelial cell viability, nor did other solvents such as
      dimethyl sulfoxide mimic the alcohol effect. So far as the physiologically
      occurring oxysterols are concerned, this effect was apparent only for oxysterols
      oxidized at the steran ring. The possibility of alcohol facilitating the uptake
      of oxysterols into the cell was not supported by the data from an uptake study
      with radiolabeled compounds. Finally, alcohol in combination with oxysterols did
      cause a dramatic increase in cytosolic calcium influx. Blockage of calcium influx
      by the calcium channel blocker aurintricarboxylic acid or the calcium chelator
      ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid abrogated
      the alcohol-mediated enhancement of oxysterol toxicity. We describe for the first
      time a mechanistic concept explaining possible adverse effects of alcohol in
      conjunction with physiologically occurring oxysterols on atherogenesis.

PMID- 11231927
TI  - Thrombomodulin promoter mutations, venous thrombosis, and varicose veins.
AB  - We analyzed the distal promoter region of the thrombomodulin (TM) gene
      (nucleotides -300 to -2052) in subjects from the Paris Thrombosis Study
      (PATHROS), a French case-control study of venous thrombosis, to identify
      polymorphisms that might modify TM gene expression. Eight novel mutations were
      found in the 40 DNA samples initially screened. Two of these mutations (-1748G/C
      and -1208/-1209 del TT) were frequent. One rare transition (-1166G/A) might have
      functional consequences owing to its position. These 3 mutations were screened
      for in the entire study population of 327 patients and 398 controls. None of the
      3 was significantly associated with thrombosis. Interestingly, the -1208/-1209 TT
      deletion was associated with varicose veins in the patients. This mutation was in
      tight linkage disequilibrium with the +1418 C/T change in the coding sequence, a
      known polymorphism that predicts an Ala 455 Val substitution in the sixth
      epidermal growth factor-like TM module, a domain previously implicated in the
      proliferative functions of TM. This linkage suggests that the Ala 455 Val
      mutation may promote changes in these functions and thus be involved in varicose
      vein formation.

PMID- 11231928
TI  - Influence of plasma fibrinogen levels on the incidence of myocardial infarction
      and death is modified by other inflammation-sensitive proteins: a long-term
      cohort study.
AB  - Inflammation may play an important role in atherosclerotic disease. Plasma
      fibrinogen is an established predictor of cardiovascular events. The aim of this
      study was to evaluate whether other inflammation-sensitive plasma proteins modify
      this prediction. We studied the incidence of cardiac events and death in men in
      relation to fibrinogen levels alone and in combination with other proteins. The
      study was based on 6075 men, who were, on average, 46 years old at the time of
      the screening examination, which included the quantitative assessment of plasma
      levels of fibrinogen, orosomucoid, alpha(1)-antitrypsin, haptoglobin, and
      ceruloplasmin. The concentration of each protein was divided into quartiles for
      each. This classification made it possible to identify 4 groups, ie, men in the
      first fibrinogen quartile and at the same time either not belonging to the fourth
      quartile of any of the other proteins (Q1/No group) or also belonging to the
      fourth quartile of >/=1 of the additional proteins (Q1/Yes group) and
      corresponding groups in the fourth fibrinogen quartile (Q4/No and Q4/Yes groups).
      During the follow-up, which occurred at an average of 16 years, 439 (7.2%) men
      experienced a cardiac event, and 653 (10.7%) died; 278 of these men died of
      cardiovascular diseases, with 206 deaths attributed to ischemic heart disease.
      From the lowest to the highest quartile, there was for each protein a stepwise
      increase in the incidence of cardiac events and mortality. All-cause mortality
      and cardiovascular mortality were significantly higher in the Q4/Yes group
      compared with the Q4/No group, but they were similar in the Q4/No and Q1/Yes
      groups. The incidence of cardiac events was significantly higher in the Q1/Yes
      and Q4/Yes groups compared with the Q1/No and Q4/No groups, respectively. The
      increased cardiovascular mortality and cardiac event rates remained after
      adjustment for several confounders when the Q4/Yes and Q4/No groups were
      compared. The results suggest that the incidence of cardiac events and death due
      to cardiovascular diseases in middle-aged men predicted by plasma levels of
      fibrinogen is modified by other inflammation-sensitive proteins.

PMID- 11231931
TI  - Manometric heterogeneity in patients with idiopathic achalasia.
AB  - BACKGROUND & AIMS: In certain cases of achalasia, particularly those in early
      stages with minimal endoscopic or radiographic abnormalities, the diagnosis may
      rely on manometry, which is the most sensitive test for the disease. The aim of
      this study was to critically evaluate the manometric criteria in a population of
      patients with idiopathic achalasia. METHODS: Clinical histories and manometric
      recordings of 58 patients with idiopathic achalasia and 43 control subjects were
      analyzed with regard to esophageal body contraction amplitude, peristaltic
      effectiveness in terms of both completeness and propagation velocity, lower
      esophageal sphincter (LES) resting pressure, LES relaxation pressure, and
      intraesophageal-intragastric pressure gradient. Variants of achalasia were
      defined by finding manometric features that significantly differed from the
      remainder of achalasia patients, such that the diagnosis might be questioned.
      RESULTS: Four manometrically distinct variants were identified. These variants
      were characterized by (1) the presence of high amplitude esophageal body
      contractions, (2) a short segment of esophageal body aperistalsis, (3) retained
      complete deglutitive LES relaxation, and (4) intact transient LES relaxation. In
      each instance, the most extreme variant is discussed and compared with the
      remainder of the achalasia population and with controls. CONCLUSIONS: The
      significance in defining these variants of achalasia lies in the recognition that
      these sometimes confusing manometric findings are consistent with achalasia when
      combined with additional clinical data supportive of the diagnosis. Furthermore,
      such variants provide important clues into the pathophysiology of this rare
      disorder.

PMID- 11231929
TI  - Long-chain n-3 fatty acids specifically affect rat coagulation factors dependent
      on vitamin K: relation to peroxidative stress.
AB  - Fatty acids of marine origin have been shown to affect blood coagulation in the
      rat. In an attempt to gain insight into the mechanisms of this phenomenon, we
      studied the effects of dietary linseed and fish oils on the liver antioxidant
      status and plasma coagulation parameters in rats on a time-course basis. Dietary
      enrichment in eicosapentaenoic and docosahexaenoic acids resulted in strong
      hypocoagulation after only 1 week and a concomitant increase in liver lipid
      peroxidation and tocopherolquinone content. Enrichment in linolenic acid induced
      similar increases in lipid peroxidation and tocopherol catabolism but negligible
      alteration of coagulation. A significant correlation between plasma factor II
      coagulant activity and liver tocopherolquinone was found in fish oil- but not in
      linseed oil-fed rats. Although ingestion of tocopherolquinone led to high levels
      of this compound in the liver, it had only marginal effects on coagulation
      factors. Thus, it seems unlikely that this vitamin E metabolite could be involved
      in the lowering of vitamin K-dependent clotting factors through inhibition of
      gamma-glutamylcarboxylase. Rather, our results indicate that the effects of the n
      3 fatty acids of fish oil on vitamin K-dependent coagulation factors are specific
      and independent of liver tocopherolquinone levels.

PMID- 11231932
TI  - Efficacy and tolerability of racecadotril in acute diarrhea in children.
AB  - BACKGROUND & AIMS: Oral rehydration therapy is the only treatment recommended by
      the World Health Organization in acute diarrhea in children. Antisecretory drugs
      available could not be used because of their side effects, except for
      racecadotril, which is efficient in acute diarrhea in adults. METHODS: The
      efficacy and tolerability of racecadotril (1.5 mg/kg administered orally 3 times
      daily) as adjuvant therapy to oral rehydration were compared with those of
      placebo in 172 infants aged 3 months to 4 years (mean age, 12.8 months) who had
      acute diarrhea. The treatment groups were comparable in terms of age, duration of
      diarrhea, number of stools, and causative microorganism at inclusion. RESULTS:
      During the first 48 hours of treatment, patients receiving racecadotril had a
      significantly lower stool output (grams per hour) than those receiving placebo.
      The 95% confidence interval was 43%-88% for the full data set (n = 166; P =
      0.009) and 33%-75% for the per-protocol population (n = 116; P = 0.001). There
      was no difference between treatments depending on rotavirus status. Significant
      differences between treatment groups were also found after 24 hours of treatment:
      full data set (n = 167; P = 0.026) and per-protocol population (n = 121; P =
      0.015). Tolerability was good in both groups of patients. CONCLUSIONS: This study
      demonstrates the efficacy (up to 50% reduction in stool output) and tolerability
      of racecadotril as adjuvant therapy to oral rehydration solution in the treatment
      of severe diarrhea in infants and children.

PMID- 11231933
TI  - Glucagon-like peptide 2 improves nutrient absorption and nutritional status in
      short-bowel patients with no colon.
AB  - BACKGROUND & AIMS: Glucagon-like peptide 2 (GLP-2) is intestinotrophic,
      antisecretory, and transit-modulating in rodents, and it is mainly secreted from
      the intestinal mucosa of the terminal ileum and colon after food ingestion. We
      assessed the effect of GLP-2 on the gastrointestinal function in patients without
      a terminal ileum and colon who have functional short-bowel syndrome with severe
      malabsorption of wet weight (>1.5 kg/day) and energy (>2.3 MJ/day) and no
      postprandial secretion of GLP-2. METHODS: Balance studies were performed before
      and after treatment with GLP-2, 400 microg subcutaneously twice a day for 35
      days, in 8 patients (4-17 years from last bowel resection; 6 with Crohn's
      disease). Four patients received home parenteral nutrition (mean residual
      jejunum, 83 cm), and 4 did not (mean ileum resection, 106 cm). Biopsy specimens
      were taken from jejunal/ileal stomas, transit was measured by scintigraphy, and
      body composition was measured by dual-energy x-ray absorptiometry. RESULTS:
      Treatment with GLP-2 improved the intestinal absorption of energy 3.5% +/- 4.0%
      (mean +/- SD) from 49.9% to 53.4% (P = 0.04), wet weight 11% +/- 12% from 25% to
      36% (P = 0.04), and nitrogen 4.7% +/- 5.4% from 47.4% to 52.1% (P = 0.04). Body
      weight increased 1.2 +/- 1.0 kg (P = 0.01), lean body mass increased 2.9 +/- 1.9
      kg (P = 0.004), fat mass decreased 1.8 +/- 1.3 kg (P = 0.007), and 24-hour urine
      creatinine excretion increased (P = 0.02). The time to 50% gastric emptying of
      solids increased 30 +/- 16 minutes from 89 to 119 minutes (P < 0.05). Small bowel
      transit time was not changed. Crypt depth and villus height were increased in 5
      and 6 patients, respectively. CONCLUSIONS: Treatment with GLP-2 improves
      intestinal absorption and nutritional status in short-bowel patients with
      impaired postprandial GLP-2 secretion in whom the terminal ileum and the colon
      have been resected.

PMID- 11231934
TI  - Inflammatory bowel disease in spouses and their offspring.
AB  - BACKGROUND & AIMS: The rarity of inflammatory bowel disease (IBD) in both husband
      and wife is often given as an argument against an infectious origin. We
      registered conjugal instances of IBD in Northern France and in Belgium between
      1989 and 2000. METHODS: Couples were assigned to group A if both partners had
      symptoms of IBD before cohabitation, to group B if one spouse had IBD before
      cohabitation and the other experienced first symptoms afterwards, and to group C
      if both partners got the disease after cohabitation. Risk of IBD was assessed in
      their offspring. RESULTS: Thirty conjugal instances were registered. Seventeen
      were concordant for Crohn's disease and 3 for ulcerative colitis; 10 were mixed.
      Two belonged to group A, 6 to group B, and 22 to group C. In group C, IBD
      occurred in the first affected spouse an average of 9 years after cohabitation
      and in the second spouse an average of 8.5 years later. Group C conjugal forms
      were more frequent than expected by chance (P < 0.02). Fifty-four children were
      born to 25 couples; among them 9, of whom 4 were siblings, developed Crohn's
      disease at a median age of 15 years. CONCLUSIONS: The frequency of conjugal forms
      of IBD suggests an etiologic role for environmental factors. Offspring of 2
      affected parents have a high risk of developing IBD.

PMID- 11231935
TI  - Screening and surveillance colonoscopy in chronic Crohn's colitis.
AB  - BACKGROUND & AIMS: Unlike ulcerative colitis, there are few reports on the
      efficacy of surveillance colonoscopy in patients with chronic Crohn's colitis and
      therefore little agreement as to whether routine surveillance is indicated. We
      report on 259 patients with chronic Crohn's colitis who underwent screening and
      subsequent surveillance colonoscopy and biopsy since 1980. METHODS: Biopsies were
      performed at 10-cm intervals and from strictures and polypoid masses. Pathology
      was classified as normal, dysplasia (indefinite, low-grade, high-grade), or
      carcinoma. RESULTS: A total of 663 examinations were performed on 259 patients.
      The median interval between examinations was 24 months; examinations were
      performed more frequently (1-6 months) in patients with dysplasia on biopsy. A
      thinner-caliber colonoscope was required to complete 12% of screening
      examinations and 23% of surveillance examinations. The pediatric colonoscope
      helped increase our yield of neoplasia by 19%. The screening and surveillance
      program detected dysplasia or cancer in 16% (10 indefinite, 23 low-grade, and 4
      high-grade dysplasias and 5 cancers). A finding of definite dysplasia or cancer
      was associated with age >45 years and increased symptoms. By life table analysis,
      the probability of detecting dysplasia or cancer after a negative screening
      colonoscopy was 22% by the fourth surveillance examination. CONCLUSIONS:
      Colonoscopic surveillance should be strongly considered in chronic extensive
      Crohn's colitis.

PMID- 11231936
TI  - Comparative study of ASCA (Anti-Saccharomyces cerevisiae antibody) assays in
      inflammatory bowel disease.
AB  - BACKGROUND & AIMS: Anti-Saccharomyces cerevisiae antibody (ASCA) is a serologic
      marker associated with Crohn's disease (CD). Although there is still discussion
      on its clinical value, several companies each promote their own ASCA assay to be
      used in the gastroenterologist's practice at considerable expense. The aim of
      this study was to determine whether different ASCA assays agree sufficiently well
      for the results to be used interchangeably. METHODS: Blood obtained from a large
      cohort of IBD patients with inflammatory bowel disease (IBD; 100 with CD, 100
      with ulcerative colitis [UC]) and 178 controls (100 healthy blood donors and 78
      patients with non-IBD diarrheal illnesses) was studied with 4 different ASCA
      assays. Sensitivity, specificity, and positive predictive value were compared.
      Agreement between assays was evaluated. RESULTS: Sensitivity of ASCA for CD
      ranged between 41% and 76%. Sensitivity was inversely related to specificity and
      positive predictive value. Results correlated well overall (range = 0.54-0.90)
      and the different ROC curves showed good agreement. When recalculated cutoff
      points were used, interchangeability increased. However, large differences were
      seen when absolute values were compared. CONCLUSIONS: A large range in
      sensitivities and specificities of ASCA for CD is seen with different ASCA
      assays, mainly as a consequence of the cutoff value chosen for each individual
      assay. Although agreement between and within assays is good, caution is important
      when absolute values are used. Standardization of ASCA measurements is greatly
      needed.

PMID- 11231937
TI  - Evidence for inflammatory bowel disease of a susceptibility locus on the X
      chromosome.
AB  - BACKGROUND & AIMS: The technique of genomewide scanning has been applied
      successfully in inflammatory bowel disease (IBD). A number of putative
      susceptibility loci have been identified through genomewide searches including
      replicated regions of linkage on chromosomes 12, 16, 6 (the HLA region), and 14.
      We have investigated the contribution of the X chromosome in 145 Belgian affected
      relative pairs. METHODS: In the first stage of the study, 79 (68 CD, 11 mixed)
      sibling pairs were genotyped at 12 microsatellite markers covering the X
      chromosome. In the second stage, 10 additional markers in the X-pericentromeric
      region were studied in the families involved in stage 1 together with 62
      additional families (52 sibling pairs, 14 second-degree relative pairs). RESULTS:
      In the first stage, evidence for linkage was found over a 30-cM pericentromeric
      region spanning dXs991, dXs990, and dXs8096 (multipoint maximum LOD score in the
      CD subgroup, 2.5; P = 0.0003). The remainder of the X chromosome was excluded
      (exclusion under LOD-2) for a locus with lambda(s) = 2. Fine mapping in the
      second stage confirmed linkage, and narrowed and shifted the linked region to
      Xq21.3 around dXs1203 (nonparametric linkage [NPL], 2.90; P = 0.0017). The NPL-1
      interval around the linkage peak comprises 19.7 cM. CONCLUSIONS: These data
      provide suggestive evidence for the presence and chromosomal location of an X
      linked susceptibility gene in IBD.

PMID- 11231938
TI  - Backwash ileitis is strongly associated with colorectal carcinoma in ulcerative
      colitis.
AB  - BACKGROUND & AIMS: Commonly accepted risk factors for colorectal carcinoma (CRC)
      in ulcerative colitis are duration and extent of disease. By identifying still
      unknown risk factors, surveillance strategies may be improved further. We
      investigated whether backwash ileitis is also a factor associated with CRC in
      ulcerative colitis. METHODS: Five hundred ninety consecutive patients with
      ulcerative colitis who received restorative proctocolectomy were classified into
      3 groups: (1) pancolitis with backwash ileitis, (2) pancolitis without backwash
      ileitis, and (3) left-sided colitis. The association with CRC was analyzed in
      these 3 groups of patients. As further risk factors, we investigated disease
      duration, dysplasia, primary sclerosing cholangitis, age at diagnosis of disease,
      disease activity, and gender. Univariate and multivariate logistic regression
      were used for analysis. RESULTS: CRC was diagnosed in 11.2% of all patients. CRC
      was found in 29.0% of 107 patients in group 1, compared with 9.0% of 369 patients
      in group 2, and in 1.8% of 114 patients in group 3 (P < 0.001). Cancer patients
      in group 1 showed significantly more multiple tumor growth (45.2%) than patients
      in group 2 (24.2%) and group 3 (0%) (P = 0.041). Estimating the relative risk for
      CRC in the multivariate analysis, patients in group 1 showed a significantly
      higher odds ratio than patients in groups 2 and 3 (odds ratio: 19.36 vs. 9.58 vs.
      1; P < 0.001). High-grade dysplasia, low-grade dysplasia, disease duration of
      more than 10 years, and disease duration of less than 10 years in patients older
      than 45 years were further factors with significantly increased risk (odds
      ratios: 21.69, 6.36, 3.63, 4.37), but primary sclerosing cholangitis was not (P =
      0.080). However, primary sclerosing cholangitis was strongly associated with
      backwash ileitis. CONCLUSIONS: There is a strong association of backwash ileitis
      with CRC in patients with ulcerative colitis who undergo proctocolectomy. The
      predictive value of backwash ileitis for CRC and premalignant dysplasia in
      patients with ulcerative colitis should be investigated in future studies based
      on colonoscopic surveillance.

PMID- 11231939
TI  - Racial and ethnic colorectal cancer patterns affect the cost-effectiveness of
      colorectal cancer screening in the United States.
AB  - BACKGROUND & AIMS: Colorectal cancer screening beginning at age 50 is recommended
      for all Americans considered at "average" risk for the development of colorectal
      cancer. METHODS: We used 1988-1995 California Cancer Registry data to compare the
      cost-effectiveness of two 35-year colorectal cancer screening interventions among
      Asians, blacks, Latinos, and Whites. RESULTS: Average annual age-specific
      colorectal cancer incidence rates were highest in blacks and lowest in Latinos.
      Screening beginning at age 50 was most cost-effective in blacks and least cost
      effective in Latinos (measured as dollars spent per year of life saved), using
      annual fecal occult blood testing (FOBT) combined with flexible sigmoidoscopy
      every 5 years and using colonoscopy every 10 years. A 35-year screening program
      beginning in blacks at age 42, whites at age 44, or Asians at age 46 was more
      cost-effective than screening Latinos beginning at age 50. CONCLUSIONS:
      Colorectal cancer screening programs beginning at age 50, using either FOBT and
      flexible sigmoidoscopy or colonoscopy in each racial or ethnic group, are within
      the $40,000-$60,000 per year of life saved upper cost limit considered acceptable
      for preventive strategies. Screening is most cost-effective in blacks because of
      high age-specific colorectal cancer incidence rates.

PMID- 11231940
TI  - Prevalence of high-grade dysplasia and cancer in the anal canal in human
      papillomavirus-infected individuals.
AB  - BACKGROUND & AIMS: The incidence of anal cancer is higher in patients with anal
      canal condyloma, a sexually transmitted disease, than in the general population.
      We determined the prevalence of anal dysplasia and cancer in patients with anal
      canal condyloma with respect to human immunodeficiency virus (HIV) status,
      immunity status, and human papillomavirus types. METHODS: In 174 consecutive
      patients (114 HIV positive, 60 HIV negative) with anal canal condyloma, lesions
      were cured, and the patients were then followed up prospectively. Langerhans
      cells (LCs) in normal anal mucosa were quantified, and viruses (Epstein-Barr
      virus, cytomegalovirus, human simplex virus 1, and various human papillomavirus
      [HPV] types) were characterized on inclusion. During follow-up (median 26
      months), relapsed condylomas were resected and examined histologically. HIV load
      and CD4 T-lymphocyte counts in serum were determined at each visit. RESULTS:
      Several factors differed significantly between HIV-positive and HIV-negative
      patients: LCs/mm anal tissue (15 vs. 30), oncogenic HPV (27% vs. 13%), other
      current anal infections (44% vs. 0%), and sex ratio (93% vs. 73% male). During
      follow-up, condylomas relapsed in 75% of the HIV-positive patients, with 19 high
      grade dysplasias (HGDs) and 1 invasive carcinoma, but in only 6% of HIV-negative
      patients, with 1 HGD. Male sex, HIV positivity, and <15 LCs/mm tissue were
      independent risk factors for condyloma relapse. HIV positivity, HGD before
      inclusion, and condyloma relapse were independent risk factors for HGD and
      cancer. Serum HIV load was associated with relapse, whereas CD4 T-lymphocyte
      counts were not. CONCLUSIONS: The prevalence of HGD and carcinoma is higher in
      HIV-positive than in HIV-negative patients, probably because of HPV activity. HIV
      positive patients with high serum HIV load and/or a history of anal dysplasia
      should be examined by anoscopy, and condylomas should be analyzed histologically.

PMID- 11231941
TI  - Rofecoxib, a COX-2 inhibitor, does not inhibit human gastric mucosal
      prostaglandin production.
AB  - BACKGROUND & AIMS: Rofecoxib, an inhibitor of the inducible cyclooxygenase (COX)
      2 enzyme, appears not to cause acute gastroduodenal injury or chronic ulceration.
      To attribute this to COX-2 selectivity with sparing of gastric mucosal
      prostaglandin synthesis requires direct proof. METHODS: Twenty-four healthy,
      nonsmoking Helicobacter pylori-negative volunteers were randomized to 1 of 2
      separate concurrent blinded crossover studies. Sixteen volunteers received
      rofecoxib, 50 mg once daily, for 5 days in one treatment period and placebo in
      the other. Eight volunteers similarly received naproxen, 500 mg twice daily, and
      placebo. On day 5 of each period, antral mucosal prostaglandin E2 (PGE2)
      synthesis was measured by radioimmunoassay after vortexing for 3 minutes. Whole
      blood COX-1 activity was measured as serum thromboxane (TXB)2- and COX-2 activity
      as lipopolysaccharide (LPS)-induced PGE2. RESULTS: Naproxen decreased gastric
      mucosal PGE2 synthesis by 65% (90% confidence interval [CI], 53%-74%; P = 0.001
      vs. placebo) in contrast to an 18% increase after rofecoxib (90% CI, -11% to 57%;
      P = 0.313 vs. placebo). Naproxen also significantly inhibited both serum TXB2 by
      94% and LPS-induced PGE2 production by 77% (both P < or = 0.002 vs. placebo), but
      rofecoxib only inhibited COX-2-dependent LPS-induced PGE(2) (by 79%; P < 0.001
      vs. placebo). CONCLUSIONS: Rofecoxib (50 mg) lacked naproxen's ability to reduce
      the availability of gastroprotective prostaglandins.

PMID- 11231942
TI  - Synergistic efficacy of 3n-butyrate and 5-fluorouracil in human colorectal cancer
      xenografts via modulation of DNA synthesis.
AB  - BACKGROUND & AIMS: Butyrate, produced in the colon lumen, maintains mucosal cell
      homeostasis. Poorly diffusible, its access is compromised in growing colon
      cancers and absent in distant metastases. Butyrate regulates DNA synthesis. We
      postulated that systemic administration of butyrate should reduce colon cancer
      growth and enhance 5-fluorouracil (5-FU) efficacy. METHODS: A stable derivative
      of butyrate (3n-But) was used. The antitumoral efficacy of 5-FU and 3n-But, alone
      or combined, was evaluated in human colorectal cancers (hCRCs) subcutaneously,
      orthotopically, or intrasplenically grafted into nude mice. Thymidylate synthase
      (TS) and thymidine kinase (TK) mRNA expression, proliferation, apoptosis, and
      cell cycle alterations were studied. RESULTS: In vivo, 5-FU alone inhibited
      growth of only 3 of the 12 hCRCs tested and 3n-But alone had no effect; the 5
      FU/3n-But combination inhibited growth of all 16 hCRCs tested. The hCRCs differed
      in their p53 and microsatellite instability status. 5-FU/3n-But decreased TK and
      TS mRNA expression by 20- and 40-fold, respectively, and TS activity by 75%,
      stopped cell proliferation without affecting cell differentiation, and
      significantly enhanced apoptosis. 3n-But potentiated the efficacy of Tomudex and
      methotrexate, 2 TS inhibitors, but not that of oxaliplatin. In vitro, 5-FU/3n-But
      inhibited [3H]thymidine but not bromodeoxyuridine incorporation and induced
      apoptosis in hCRC cell lines. Cells treated with 5-FU/3n-But did not accumulate
      in G1 nor in S phase of the cell cycle, while 5-FU and 3n-But arrested the cycle
      in S and in G1 phase, respectively. 3n-But prevented the cell rescue from 5-FU
      induced cytotoxicity by uridine or thymidine. CONCLUSIONS: 3n-But and TS
      inhibitors acted synergistically against colorectal cancers, independently of the
      genetic alterations of the hCRCs. The mechanism of action of 5-FU/3n-But could be
      enhanced reduction of TS and prevention of thymidine salvage in DNA synthesis.

PMID- 11231943
TI  - Resistance to butyrate-induced cell differentiation and apoptosis during
      spontaneous Caco-2 cell differentiation.
AB  - BACKGROUND & AIMS: The short-chain fatty acid butyrate induces cell cycle arrest,
      differentiation, and apoptosis in colon cancer cells, but often induces opposite
      effects in normal colonic epithelial cells. We determined whether response to
      butyrate is dependent on the basal differentiation status of colonic epithelial
      cells. METHODS: Caco-2 cells at progressive stages of differentiation were
      treated with butyrate, and endpoints were measured. RESULTS: Response of Caco-2
      cells to butyrate was dependent on their differentiation status. Butyrate
      maximally stimulated cell cycle arrest, apoptosis, alkaline phosphatase activity,
      transepithelial resistance, cell migration, urokinase receptor expression, and
      interleukin 8 secretion in undifferentiated Caco-2 cells, whereas differentiated
      Caco-2 cells were essentially resistant to these effects. Consistently, butyrate
      selectively induced histone hyperacetylation in undifferentiated Caco-2 cells.
      This resistance was also observed during HT29cl.19A cell differentiation, but not
      in the nondifferentiating SW620 cell line. Finally, the rate of butyrate use
      significantly increased as Caco-2 cells underwent spontaneous differentiation.
      CONCLUSIONS: Colonic epithelial cells become progressively more refractory to the
      effects of butyrate during absorptive cell differentiation. We postulate that
      this resistance is caused by the rapid use of butyrate by differentiated Caco-2
      cells, which likely results in low intracellular concentrations and subsequently
      in its inability to inhibit histone deacetylase.

PMID- 11231944
TI  - Continuous stimulation by normal luminal bacteria is essential for the
      development and perpetuation of colitis in Tg(epsilon26) mice.
AB  - BACKGROUND & AIMS: Normal resident bacteria are required for development of
      colitis in several rodent models. We determined whether bacterial stimulation is
      necessary for both induction and perpetuation of mucosal inflammation and T-cell
      activation in Tg(epsilon26) mice, in which transplantation of wild-type bone
      marrow (BM-->Tg(epsilon26)) causes colitis under specific pathogen-free (SPF)
      conditions. METHODS: BM from (C57BL/6 X CBA/J) F1 mice was transplanted into
      germfree (GF) or SPF Tg(epsilon26) mice. Mesenteric lymph node (MLN) cells from
      these mice were then transferred into SPF or GF recipients. Colitis and
      activation of MLN cells were measured by histologic scores, membrane marker
      analysis, and intracellular cytokine staining. Cytokine secretion by MLN cells
      stimulated by anti-CD3 or by luminal or epithelial antigens was measured by
      ELISA. RESULTS: Colitis did not develop when BM was transferred into GF recipient
      mice (BM-->GF Tg(epsilon26)). T lymphocytes that secreted interferon gamma upon
      activation were present in the MLN of BM-->GF Tg(epsilon26) mice, albeit in lower
      frequency than in control BM-->SPF Tg(epsilon26) mice. Furthermore, transfer of
      MLN cells from BM-->SPF Tg(epsilon26) mice into SPF Tg(epsilon26) recipients
      induced active colitis, but not if the same cells were transferred into GF
      Tg(epsilon26) recipients. Although CD4 T cells were detected in the colonic
      mucosa of GF recipients, no inflammation was observed for at least 31 weeks. In a
      reciprocal experiment, MLN cells from BM-->GF Tg(epsilon26) mice without colitis
      transferred disease to SPF Tg(epsilon26) recipients within 2-4 weeks.
      CONCLUSIONS: Activated T cells are present in the mucosa of BM-->GF Tg(epsilon26)
      mice but are incapable of inducing disease unless colonic bacteria are present.
      Moreover, pathogenic T cells require the continuous presence of colonic bacteria
      to sustain colitis.

PMID- 11231945
TI  - Murine ileitis after intracellular parasite infection is controlled by TGF-beta
      producing intraepithelial lymphocytes.
AB  - BACKGROUND & AIMS: Acute inflammatory ileitis occurs in susceptible (C57BL/6)
      mice after oral infection with Toxoplasma gondii. Overproduction of interferon
      (IFN)-gamma and synthesis of nitric oxide mediate the inflammation. We evaluated
      the role of transforming growth factor (TGF)-beta produced by intraepithelial
      lymphocytes (IELs) in this process. METHODS: We analyzed the histologic and
      immunologic consequences of adoptive transfer of antigen-primed IELs into
      susceptible mice treated with anti-TGF-beta before oral challenge with T. gondii
      cysts. An in vitro coculture of enterocytes and IELs assessed the production of
      chemokines and cytokines in the presence of anti-TGF-beta. RESULTS: Antigen
      primed IELs prevent acute ileitis in susceptible mice that is reversed with anti
      TGF-beta. Resistant mice (CBA/J) develop ileitis after treatment with anti-TGF
      beta. Antigen-primed IELs can induce systemic immunosuppression as measured by
      depressed IFN-gamma production. In vitro, primed IELs reduce the production of
      inflammatory chemokines by infected enterocytes and IFN-gamma by splenocytes.
      CONCLUSIONS: Regulation of the ileal inflammatory process resulting from T.
      gondii is dependent on TGF-beta-producing IELs. The IELs are an essential
      component in gut homeostasis after oral infection with this parasite.

PMID- 11231946
TI  - Enhanced survival and mucosal repair after dextran sodium sulfate-induced colitis
      in transgenic mice that overexpress growth hormone.
AB  - BACKGROUND & AIMS: Growth hormone (GH) is used as therapy for inflammatory bowel
      disease (IBD), but the specific effects on intestine are unknown. Transgenic mice
      overexpressing GH (MT1-bGH-TG) were used to test whether increased plasma GH
      levels alter inflammation or crypt damage during dextran sodium sulfate (DSS)
      induced colitis. METHODS: MT1-bGH-TG and wild-type (WT) littermates were given 3%
      DSS for 5 days followed by up to 10 days of recovery. Colitis and epithelial cell
      proliferation were evaluated histologically. Plasma insulin-like growth factor
      (IGF)-I and colonic IGF-I, interleukin (IL)-1beta, and intestinal trefoil factor
      (ITF) messenger RNAs (mRNAs) were measured. RESULTS: DSS induced similar disease
      onset in MT1-bGH-TG and WT. More MT1-bGH-TG survived than WT. By recovery day 7,
      MT1-bGH-TG had less inflammation and crypt damage, elevated plasma IGF-I, and
      increased colonic ITF expression relative to WT. Colonic IL-1beta was elevated in
      DSS-treated MT1-bGH-TG and WT, but IL-1beta mRNA abundance correlated with
      disease only in WT. MT1-bGH-TG showed earlier increases in epithelial cell
      proliferation than WT during recovery but only WT showed atypical repair.
      CONCLUSIONS: GH does not alter susceptibility to acute DSS-induced colitis but
      enhances survival, remission of inflammation, and mucosal repair during recovery.
      GH therapy may be beneficial during active IBD by improving mucosal repair.

PMID- 11231947
TI  - Tachykinin-dependent and -independent components of peristalsis in the guinea pig
      isolated distal colon.
AB  - BACKGROUND & AIMS: In the intestine, tachykinins regulate motility by
      participating in neuromuscular and neuro-neuronal transmission. The aim of this
      study was to test the hypothesis that colonic propulsion is regulated by an
      interplay between tachykinergic and cholinergic transmission. METHODS: Propulsion
      was elicited by intraluminal distention of a thin rubber balloon, which traveled
      from the oral to the anal end of guinea pig isolated distal colon segments. The
      overall contribution of endogenous tachykinins to colonic propulsion was examined
      by blocking NK1, NK2, and NK3 receptors simultaneously. RESULTS: NK2-receptor
      blockade by MEN 11420 inhibited propulsion, whereas blockade of NK(1) by SR
      140333 or of NK3 receptors by SR 142801 had minor effects on motility. Blockade
      of muscarinic or nicotinic receptors by hyoscine or hexamethonium decelerated
      peristalsis up to propulsion arrest. In the presence of partial muscarinic
      receptor blockade, the NK1-receptor antagonist SR 140333 and the NK2-receptor
      antagonist MEN 11420 markedly inhibited propulsion. Propulsion was also inhibited
      by the NK3-receptor antagonist SR 142801 in the presence of partial nicotinic
      receptor blockade. The simultaneous administration of the 3 tachykinin
      antagonists inhibited propulsion by 50%. CONCLUSIONS: This study demonstrates the
      existence of an interplay between tachykinergic and cholinergic pathways during
      peristalsis and the importance of endogenous tachykinins acting at multiple
      receptor sites in the control of colonic propulsion.

PMID- 11231948
TI  - Octreotide for acute esophageal variceal bleeding: a meta-analysis.
AB  - BACKGROUND & AIMS: Studies of octreotide have not demonstrated a consistent
      benefit in efficacy or safety compared with conventional therapies. This study
      statistically pooled existing trials to evaluate the safety and efficacy of
      octreotide for esophageal variceal hemorrhage. METHODS: We identified randomized
      trials of octreotide for variceal hemorrhage from computerized databases,
      scientific meeting abstracts, and the manufacturer of octreotide. Blinded
      reviewers abstracted the data, and a meta-analysis was performed. RESULTS:
      Octreotide improved control of esophageal variceal hemorrhage compared with all
      alternative therapies combined (relative risk [RR], 0.63; 95% confidence interval
      [CI], 0.51-0.77); vasopressin/terlipressin (RR, 0.58; 95% CI, 0.42-0.81); or no
      additional intervention/placebo (among patients that received initial
      sclerotherapy/banding before randomization) (RR, 0.46; 95% CI, 0.32-0.67).
      Octreotide had comparable efficacy to immediate sclerotherapy for control of
      bleeding (RR, 0.94; 95% CI, 0.55-1.62), fewer major complications than
      vasopressin/terlipessin (RR, 0.31; 95% CI, 0.11-0.87), and a complication profile
      comparable to no intervention/placebo (RR, 1.06; 95% CI, 0.72-1.55). No specific
      alternative therapy demonstrated a mortality benefit. CONCLUSIONS: These results
      favor octreotide over vasopressin/terlipressin in the control of esophageal
      variceal bleeding and suggest it is a safe and effective adjunctive therapy after
      variceal obliteration techniques. Trials are needed to determine the optimal
      dose, route, and duration of octreotide treatment.

PMID- 11231949
TI  - Differential gene expression between chronic hepatitis B and C hepatic lesion.
AB  - BACKGROUND & AIMS: Complementary DNA (cDNA) microarray technology allows
      simultaneous expression analysis of hundreds to thousands of genes. We applied
      the cDNA microarray technique to clarify gene expression profiles in chronic
      viral hepatitis tissue lesions. METHODS: We made cDNA microarrays consisting of
      1080 human cDNAs and analyzed gene expression using labeled cDNAs prepared from 6
      normal, 12 chronic hepatitis B, and 14 chronic hepatitis C liver tissues.
      Relative expression ratios of individual genes were obtained by comparing
      hybridization of Cy5-labeled cDNAs from chronic hepatitis lesions and Cy3-labeled
      cDNA from normal liver tissue. RESULTS: Hierarchical clustering analysis of the
      gene expression profiles in 26 patients showed that the patients were clustered
      into 2 groups with respect to similarities in differentially expressed genes.
      Hepatitis B and C virus infection, but not age, sex, or histology of hepatitis,
      were significant factors determining clustering (P < 0.05). In hepatitis B tissue
      lesions, genes involved in inflammation were predominant, whereas in hepatitis C,
      expression of anti-inflammatory response genes was relatively dominant.
      CONCLUSIONS: These findings shed new light on the possible differential molecular
      mechanisms in the pathogenesis of hepatitis caused by hepatitis B virus and
      hepatitis C virus infection, from which hepatocellular carcinoma frequently
      develops.

PMID- 11231950
TI  - A mutation of the Wilson disease protein, ATP7B, is degraded in the proteasomes
      and forms protein aggregates.
AB  - BACKGROUND & AIMS: Wilson disease is a genetic disorder characterized by the
      accumulation of copper in the body as a result of a defect of copper excretion
      from hepatocytes. The intracellular localization of the Wilson disease gene
      product, ATP7B, was recently identified as the late endosomes. Various mutations
      have been documented in patients with Wilson disease. The clinical manifestations
      vary greatly among the patients; however, there is little information on the
      genotype-phenotype correlation. METHODS: We investigated the distribution of a
      common ATP7B mutant His1069Gln and a mutant Asp1270Ser by expressing the mutants
      tagged with green fluorescent protein in Huh7 and HEK293 cells. Intracellular
      organelles were visualized by fluorescence microscopy. RESULTS: Although the wild
      type ATP7B and Asp1270Ser mutant localized in the late endosomes, His1069Gln
      mutant did not locate in the late endosomes and was degraded by the proteasomes
      in the cytoplasm. Furthermore, His1069Gln formed aggresomes composed of the
      degradates and intermediate filaments at the microtubule-organizing center. These
      aggresomes were similar to Mallory bodies on electron microscopy. CONCLUSIONS:
      The different protein properties of ATP7B mutants may explain the variety of
      clinical spectrums in patients with Wilson disease.

PMID- 11231951
TI  - Octreotide potentiates PKC-dependent vasoconstrictors in portal-hypertensive and
      control rats.
AB  - BACKGROUND & AIMS: The effect of octreotide on vascular tone in the superior
      mesenteric artery (SMA) was studied in portal-hypertensive (portal vein-ligated)
      and sham-operated rats. METHODS: In vitro-perfused SMA vascular beds were tested
      for the cumulative dose-response to octreotide at baseline conditions and after
      preconstriction with different vasoconstrictors (alpha1-agonist methoxamine,
      endothelin [ET-1], phorbol ester [PdBu], and potassium chloride [KCl]). RESULTS:
      Octreotide did not affect baseline perfusion pressures (without preconstriction).
      alpha1-Adrenergic-, ET-1-, and PdBu-, but not KCl-, induced vasoconstriction was
      significantly potentiated by octreotide. This effect was dose-dependent and not
      different in portal vein-ligated and sham rats. Amplification of alpha1
      adrenergic vasoconstriction by octreotide was significantly enhanced by nitric
      oxide inhibition (N(W)-nitro-L-arginine, 10(-4) mol/L) as well as by removal of
      the endothelium, and was completely suppressed by inhibition of protein kinase C
      (calphostin C, 1 micromol/L), phospholipase A2 (quinacrine, 5 micromol/L), and
      cyclooxygenase (indomethacin, 20 micromol/L). CONCLUSIONS: Not directly, but in
      the presence of vasoconstrictors involving activation of protein kinase C,
      octreotide exerts a local vasoconstrictive effect on vascular smooth muscle of
      SMA. This potentiation is equipotent in portal vein-ligated and sham rats,
      immediate in onset, and mediated via phospholipase A2 and cyclooxygenase-derived
      prostanoids. This indicates that in preprandial conditions octreotide enhances
      the vasoconstrictive effect of dependent vasoconstrictors.

PMID- 11231952
TI  - Rapid increase of mucosal CD4 T cells followed by clearance of intestinal
      cryptosporidiosis in an AIDS patient receiving highly active antiretroviral
      therapy.
AB  - Highly active antiretroviral therapy (HAART) suppresses the replication of human
      immunodeficiency virus (HIV) and leads to an increase in circulating CD4 T
      lymphocytes, but its effects on other immune compartments such as the intestinal
      mucosa are not well understood. We describe a severely immunodeficient HIV
      infected patient with intractable watery diarrhea and weight loss caused by
      infection with Cryptosporidium parvum in whom we studied virologic and
      immunologic changes in both peripheral blood and the intestinal mucosa after
      initiating HAART. Mucosal biopsies were performed by rectoscopy before and at
      several time points after HAART was begun. Nucleic acids were extracted from
      rectal biopsy specimens and blood samples, and HIV RNA was measured by reverse
      transcription polymerase chain reaction. Lymphocytes were isolated from rectal
      biopsy specimens after mechanical disaggregation, and circulating and mucosal CD4
      T cells were determined by flow cytometry. HAART led to clinical recovery and
      eradication of cryptosporidiosis. In both blood and mucosa, HIV RNA decreased
      below the limit of detection and CD4 T cells increased. Mucosal CD4 T cells
      increased much faster and to much higher levels than circulating CD4 T cells. Our
      findings show a rapid repopulation of the intestinal mucosa with CD4 T cells
      after initiation of HAART that can effectively restore mucosal immunity, leading
      to eradication of opportunistic pathogens.

PMID- 11231953
TI  - Human papillomavirus type 16-associated primary squamous cell carcinoma of the
      rectum.
AB  - Primary squamous cell carcinoma (SCC) of the colorectum is an extremely rare
      malignancy of unknown etiology and pathogenesis. We describe an 87-year-old man
      with primary SCC of the rectum. Routine histology demonstrated a squamous
      metaplasia-dysplasia sequence of the rectal mucosa with subsequent malignant
      transformation. Molecular biologic analysis using polymerase chain reaction (PCR)
      and in situ hybridization revealed the presence of human papillomavirus type 16
      (HPV-16) DNA within metaplastic, dysplastic, and SCC lesions and in tumor-free
      rectal mucosa. Moreover, nested reverse-transcription PCR showed transcriptional
      activity of the viral E6/E7 oncogenes in tumor tissue and tumor-free rectal
      mucosa. By contrast, 4 typical adenocarcinomas of the rectum and their adjacent
      normal mucosa were found to be negative for HPV by nested PCR. In line with the
      well-established concept of HPV-associated anogenital carcinogenesis, our results
      strongly suggest an etiologic role of HPV-16 in the pathogenesis of the
      metaplasia-dysplasia-SCC sequence in the case described.

PMID- 11231954
TI  - Anti-tumor necrosis factor monoclonal antibody therapy for gastrointestinal
      Behcet's disease: a case report.
AB  - Behcet's disease (BD) is a multisystem immune-mediated inflammatory disorder that
      involves the intestine in 3%-26% of cases. Corticosteroids, 5-aminosalicylic acid
      derivatives, immunomodulators, and more recently thalidomide and pentoxifylline
      have been used to treat BD with varying degrees of success. Tumor necrosis factor
      (TNF)-alpha is believed to play a pivotal role in this T helper cell type 1 (Th1)
      mediated disease. Infliximab, a chimeric monoclonal antibody to TNF-alpha, has
      been demonstrated to be an effective therapy for Crohn's disease and rheumatoid
      arthritis, 2 other Th1-mediated disorders. We describe a patient with chronically
      active, steroid-dependent BD involving the gastrointestinal tract who received 4
      doses of infliximab during a 6-month period. Because most of her symptoms were
      gastrointestinal, the Crohn's Disease Activity Index (CDAI) was used to assess
      response. A rapid and dramatic improvement in both gastrointestinal and
      extraintestinal symptoms was observed. The CDAI score decreased from 270 points
      (preinfusion) to 13 points by week 2, and remission was sustained despite
      complete withdrawal of steroids. Colonoscopy performed 10 weeks after the first
      infusion showed marked endoscopic and histologic improvement. This report
      suggests that infliximab may be an effective new therapy for gastrointestinal BD,
      and perhaps other manifestations of BD as well.

PMID- 11231955
TI  - Molecular anatomy and pathophysiologic implications of drug resistance in
      hepatitis B virus infection.
AB  - Synthesis of the hepatitis B virus (HBV) DNA genome occurs within the viral
      nucleocapsid in a mechanistically ordered fashion. The nucleocapsid contains
      small pores that permit influx of nucleotide triphosphates and metabolites of
      nucleoside analogues such as lamivudine for DNA synthesis. Lamivudine is a potent
      inhibitor of HBV and human immunodeficiency virus (HIV) reverse transcriptases,
      but substitutions of isoleucine or valine for methionine within the tyrosine
      methionine-aspartate-aspartate (YMDD) motif are associated with virologic and
      clinical resistance to lamivudine therapy. Under lamivudine selection pressure,
      the high viral production rate and the low fidelity viral polymerase contribute
      to frequent development of the YMDD mutants. However, the pattern and dynamics of
      emergence of the mutant viruses over the wild-type virus are determined by
      multiple factors including replication efficiency, host immune response, and
      availability of replication space. Structural modeling of HIV reverse
      transcriptase has permitted key insights into the molecular basis of lamivudine
      resistance of HBV based on evolutionary relatedness of HIV and HBV. The side
      groups of isoleucine and valine of the YMDD mutants sterically prevent lamivudine
      from appropriately configuring into the nucleotide binding site of the reverse
      transcriptase. Aminotransferase flares are associated with lamivudine therapy and
      may signify clinical resistance with emergence of YMDD mutants. They may also
      herald the recovery phase with seroconversion and viral clearance. Reconstitution
      of the endogenous anti-HBV immune response may be equally important in the
      control of viral replication by lamivudine and other nucleoside analogues.

PMID- 11231956
TI  - Acute flares in chronic hepatitis B: the natural and unnatural history of an
      immunologically mediated liver disease.
AB  - Acute flares in chronic hepatitis B are common and may be caused by a number of
      identifiable and potentially treatable factors. The common link for many of these
      exacerbation episodes is a change in the immunologic response to hepatitis B
      virus (HBV), and this may have no identifiable cause or be triggered by an
      increase in viral replication or genotypic change. It is important to keep in
      mind the clinical situations in which patients are at increased risk of
      reactivated infection and secondary exacerbations. Reactivation is frequently
      induced by medical treatments such as cancer chemotherapy, antirejection drugs
      used in organ transplantation, and corticosteroids. The immunologic flares that
      often result from sudden withdrawal of these medications can be life-threatening
      unless recognized and treated promptly with antivirals, and there is increasing
      experience that preemptive antiviral treatment can diminish their occurrence and
      improve the outcome. The experience with lamivudine and other nucleoside
      analogues has increased our understanding of the molecular events behind
      hepatitis flares that occur when chronic hepatitis B is treated with drugs that
      potently inhibit HBV DNA polymerase. However, not all flares are explainable by
      events related to HBV infection alone. Depending on the population studied, as
      many as 20%-30% of flares may be caused by infection with other hepatotropic
      viruses, and this situation may inhibit HBV replication. Proper understanding of
      the etiology and effective treatment of acute flares in chronic hepatitis B
      requires an appreciation of high-risk clinical situations, assessment of HBV
      replication status, and testing for other viruses when appropriate.

PMID- 11231957
TI  - American Gastroenterological Association medical position statement: guidelines
      for the evaluation of food allergies.

PMID- 11231958
TI  - AGA technical review on the evaluation of food allergy in gastrointestinal
      disorders. American Gastroenterological Association.

PMID- 11231959
TI  - GLP-2 as therapy for the short-bowel syndrome.

PMID- 11231960
TI  - Colorectal cancer: not an equal opportunity cancer.

PMID- 11231961
TI  - Human papillomavirus infection: an emerging problem in anal and other squamous
      cell cancers.

PMID- 11231962
TI  - What's right and what's left?

PMID- 11231963
TI  - What lies beyond the view of the sigmoidoscope?

PMID- 11231964
TI  - Nutritional therapy for alcoholic hepatitis: new life for an old idea.

PMID- 11231965
TI  - Manipulating intestinal cholesterol absorption and hepatic cholesterol and bile
      acid metabolism by activation of deorphanized nuclear receptors.

PMID- 11231968
TI  - Amiodarone-induced thyrotoxicosis.

PMID- 11231969
TI  - Compound heterozygous mutations in the gamma subunit gene of ENaC (1627delG and
      1570-1G-->A) in one sporadic Japanese patient with a systemic form of
      pseudohypoaldosteronism type 1.
AB  - The systemic form of pseudohypoaldosteronism type 1 (PHA1) is a rare autosomal
      recessive disorder with salt-wasting, hyperkalemia, metabolic acidosis, and
      multiorgan aldosterone unresponsiveness. Recently, this form of PHA1 was found to
      be caused by the loss-of-function mutations in the gene of each subunit (alpha,
      beta, and gamma) of the epithelial sodium channel (ENaC). To investigate the
      molecular basis of one sporadic Japanese patient with a systemic form of PHA1, we
      determined the nucleotide sequence of the genes of every subunit of ENaC of this
      patient. The patient was found to be a compound heterozygote for one base
      deletion in exon 12 (1627delG) in combination with 1570-1-->GA substitution at
      the 5' splice acceptor site of intron 11 in the gamma subunit gene of ENaC. The
      1627delG mutation altered a reading frame, resulting in a premature stop codon in
      exon 12. Messenger RNA from the allele harboring the splice site mutation was not
      identified by RT-PCR. In conclusion, two novel mutations in the gamma subunit
      gene of ENaC caused systemic PHA1 in the sporadic Japanese patient.
      Identification of the molecular basis of PHA1 is helpful for early diagnosis and
      understanding the pathophysiology of the disease.

PMID- 11231970
TI  - A novel mutation in the calcium-sensing receptor gene in a Chinese subject with
      persistent hypercalcemia and hypocalciuria.
AB  - Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant disorder
      characterized by high penetrance of relatively benign, lifelong persistent
      hypercalcemia and hypocalciuria. By contrast, neonatal severe hyperparathyroidism
      represents a life-threatening form of hypercalcemia that can cause the early
      newborn mortality if immediate intervention is not undertaken. Both disorders are
      due to inactivation mutation of the human calcium-sensing receptor (CaSR) gene on
      chromosome 3q21-24. Up to now, more than 30 mutations in the CaSR gene associated
      with FHH have been described. In this study, we analyzed one 79-yr-old male with
      hypocalciuric hypercalcemia without siblings or children to compare with an
      additional group of 50 normal Chinese subjects in Taiwan. DNA sequence analysis
      of the CaSR gene was performed. The result showed that the proband had a
      heterozygous nonsense mutation in exon 7 of the CaSR gene at codon 648 (CGA-
      >TGA/Arg-->Ter). This mutation, located in the COOH-terminal of the first
      intracellular loop of the CaSR, predicts a markedly truncated protein. We have
      identified a novel R648X mutation in the CaSR gene in one patient with FHH in
      Taiwan

PMID- 11231971
TI  - Risk of breast cancer with progestins in combination with estrogen as hormone
      replacement therapy.

PMID- 11231972
TI  - The genetics of Paget's disease of the bone.

PMID- 11231973
TI  - Why do older women with diabetes have an increased fracture risk?

PMID- 11231974
TI  - Older women with diabetes have an increased risk of fracture: a prospective
      study.
AB  - To determine whether type 2 diabetes is associated with fracture in older women,
      we analyzed data from 9654 women, age 65 yr or older, in the Study of
      Osteoporotic Fractures. Diabetes with age at onset 40 yr or older was reported by
      657 women, of whom 106 used insulin. A total of 2624 women experienced at least
      one nonvertebral fracture during an average follow-up of 9.4 yr, and 388 had at
      least one vertebral fracture during an average interval of 3.7 yr. Although
      diabetes was associated with higher bone mineral density, it was also associated
      with a higher risk of specific fractures. Compared with nondiabetics, women with
      diabetes who were not using insulin had an increased risk of hip [relative risk
      (RR), 1.82; 95% confidence interval (CI), 1.24-2.69] and proximal humerus (RR,
      1.94; 95% CI, 1.24-3.02) fractures in multivariate models controlling for age,
      body mass index, bone density, and other factors associated with fractures and
      diabetes. Insulin-treated diabetics had more than double the risk of foot
      (multivariate adjusted RR, 2.66; 95% CI, 1.18-6.02) fractures compared with
      nondiabetics. This study indicates that diabetes is a risk factor for hip,
      proximal humerus, and foot fractures among older women, suggesting that fracture
      prevention efforts should be a consideration in the treatment of diabetes.

PMID- 11231975
TI  - Soy phytoestrogens, lipid reductions, and atherosclerosis delay in ovariectomized
      primates.

PMID- 11231976
TI  - Inhibition of postmenopausal atherosclerosis progression: a comparison of the
      effects of conjugated equine estrogens and soy phytoestrogens.
AB  - Experimental evidence was sought concerning whether soy phytoestrogens (SPEs)
      inhibit postmenopausal atherosclerosis progression/extent and, if so, their
      effectiveness relative to traditional estrogen replacement therapy. Premenopausal
      cynomolgus monkeys were fed a moderately atherogenic diet (26 months) to induce
      atherosclerosis. After ovariectomy, the moderately atherogenic diet was
      continued, and they were treated (36 months) with a control diet (soy protein
      depleted of SPEs), a diet containing SPEs in soy protein isolate, or a diet
      containing SPE-depleted soy protein with conjugated equine estrogens (CEE;
      Premarin) added. SPE effects on plasma lipids were better than those of CEE
      (higher high density lipoprotein cholesterol and no increase in triglyceride).
      Relative to the control group, CEE treatment inhibited (P = 0.0001), and SPE
      treatment partially inhibited (P = 0.10) the progression of atherosclerosis
      (common iliac artery atherosclerosis before and after treatment). CEE-treated
      monkeys had much less coronary artery atherosclerosis than the controls (P =
      0.0002), whereas SPE-treated monkeys were intermediate in lesion extent between
      the controls and the CEE-treated animals (P = 0.02). Both CEE and SPE
      significantly reduced the extent of common carotid and internal carotid artery
      atherosclerosis, and the two treatment groups were not significantly different.

PMID- 11231977
TI  - Conjugated equine estrogen improves glycemic control and blood lipoproteins in
      postmenopausal women with type 2 diabetes.
AB  - The objective of this study was to determine the metabolic effects of estrogen
      replacement therapy in postmenopausal women with type 2 diabetes. Twenty-five
      postmenopausal, type 2 diabetic women completed a randomized, blinded, cross-over
      trial of conjugated equine estrogen, 0.625 mg/day, vs. placebo for 8 weeks,
      separated by a 4-week washout period. When compared with 8 weeks of placebo,
      estrogen reduced fasting serum glucose (7.2 +/- 0.3 vs. 8.4 +/- 0.4 mmol/L, P =
      0.0003), glycated hemoglobin (8.7 +/- 0.4% vs. 9.3 +/- 0.4%, P = 0.04), total
      cholesterol (5.27 +/- 0.20 vs. 5.50 +/- 0.21 mmol/L, P = 0.04), low-density
      lipoprotein cholesterol (2.47 +/- 0.13 vs. 2.69 +/- 0.14 mmol/L, P = 0.02), serum
      apolipoprotein B (114 +/- 6 vs. 121 +/- 5 mg/dL, P = 0.03), and postprandial
      glucose area under the curve (by 12%, P = 0.015). Estrogen replacement therapy
      also increased high-density lipoprotein (HDL) cholesterol (1.27 +/- 0.08 vs. 1.1
      +/- 0.07 mmol/L, P = 0.0002), high-density lipoprotein(2) cholesterol (0.41 +/-
      0.04 vs. 0.30 +/- 0.03 mmol/L, P = 0.0001), and fasting triglyceride (2.17 +/-
      0.21 vs. 1.94 +/- 0.16 mg/dL, P = 0.02) concentrations but not postprandial
      triglyceride area under the curve (P = not significant). We conclude that
      estrogen replacement therapy improves glycemic control, blood lipoproteins, and
      apolipoprotein B concentrations while modestly increasing triglyceride levels in
      postmenopausal, type 2 diabetic women.

PMID- 11231978
TI  - Differential regulation of gonadotropin secretion by testosterone in the human
      male: absence of a negative feedback effect of testosterone on follicle
      stimulating hormone secretion.
AB  - Studies of sex steroid regulation of gonadotropin secretion in the human male
      have focused primarily on the respective site(s) of negative feedback of
      testosterone (T) and estradiol (E(2)). The use of pharmacological doses of sex
      steroids in these studies has precluded conclusions about the relative roles of T
      and E(2) in gonadotropin feedback. Thus, the aims of the present study were to 1)
      determine the relative contributions of T vs. E(2) to the sex steroid component
      of gonadotropin regulation, and 2) distinguish the feedback effects of T that
      that are direct (i.e. mediated by the androgen receptor) vs. indirect (mediated
      by aromatization to E(2)). Two experimental interventions were used: 1)
      inhibition of aromatization by a selective aromatase inhibitor to examine the
      impact of selective E(2) withdrawal; and 2) acute medical castration to examine
      the effect of ablating both T and E(2). Sixteen normal (NL) men (mean age, 30.5
      +/- 2.2 yr) were studied. Nine NL subjects were treated with the aromatase
      inhibitor, anastrozole (10 mg, orally, daily, for 5 days). Twelve NL men
      underwent medical castration with ketoconazole (1-g loading dose followed by 400
      mg, orally, four times a day for 5 days). Ketoconazole-treated subjects received
      concomitant treatment with dexamethasone (0.5 mg twice daily) to prevent the
      development of adrenal insufficiency. Single blood samples were drawn daily
      between 0800-1000 h. To ensure that dexamethasone was not altering the
      gonadotropin response to sex steroid ablation by a direct pituitary effect, five
      GnRH-deficient men (mean age, 37.6 +/- 3.9 yr) underwent GnRH dose-response
      studies at baseline and after treatment with dexamethasone (0.5 mg twice daily).
      Aromatase blockade caused significant lowering of E(2) (33 +/- 3 to 14 +/- 1
      pg/mL; P: < 0.0005) with a corresponding increase in T levels (563 +/- 42 to 817
      +/- 81 ng/dL; P: < 0.05). Treatment with ketoconazole resulted in equivalent
      suppression of E(2) (41 +/- 4 to 14 +/- 1 pg/mL; P: < 0.0005), but also induced
      castrate levels of T (491 +/- 28 to 40 +/- 3 ng/dL; P: < 0.0005). Both treatment
      regimens were associated with a significant increase in gonadotropin levels. For
      LH, the percent increase in serum levels after castration was almost 3-fold
      greater than that seen after selective E(2) withdrawal (275 +/- 23% with
      ketoconazole vs. 95.6 +/- 21% with anastrozole; P: < 0.005). Despite the
      divergent changes in T levels with these two maneuvers (a marked decrease after
      ketoconazole and a significant increase with anastrozole), the percent rise in
      FSH levels was similar in the two protocols (91 +/- 6% vs. 71 +/- 7%,
      respectively; P: = NS). Inhibin B levels were unchanged after selective E(2)
      withdrawal (156 +/- 23 vs. 176 +/- 19 pg/mL), but decreased slightly with
      ketoconazole (156 +/- 15 to 131 +/- 11 pg/mL; P: < 0.05). In contrast to the
      effects of glucocorticoid administration on gonadotropin secretion in women, no
      significant changes were observed in the GnRH-deficient men treated with
      dexamethasone in terms of mean LH levels (19.8 +/- 3.2 vs. 23.3 +/- 5.4 IU/L),
      mean LH pulse amplitude after GnRH (16.0 +/- 2.5 vs. 19.0 +/- 5.1 IU/L), or mean
      FSH levels (8.0 +/- 1.9 vs. 9.2 +/- 2.4 IU/L, pre vs. post). These studies
      provide evidence of differential regulation of gonadotropin secretion by T in the
      human male. T exerts both direct and indirect feedback on LH secretion, whereas
      its effects on FSH appear to be mediated largely by aromatization to E(2). From
      these data we conclude that in terms of sex steroid feedback, E(2) is the
      predominant regulator of FSH secretion in the human male.

PMID- 11231979
TI  - Phenotypic heterogeneity in patients with familial partial lipodystrophy
      (dunnigan variety) related to the site of missense mutations in lamin a/c gene.
AB  - The lamin A/C (LMNA) gene has recently been reported to be mutated in familial
      partial lipodystrophy, Dunnigan variety (FPLD). We found mutations within exon 8
      of LMNA (R482Q, R482W, and G465D) in 12 families with typical FPLD and in exon 11
      (R582H) in 1 atypical family. To investigate phenotypic heterogeneity, we
      compared body fat distribution, using anthropometry and whole body magnetic
      resonance imaging, and metabolic parameters in women with atypical and typical
      FPLD. Compared with women with typical FPLD, the two sisters with atypical FPLD
      had less severe loss of sc fat from all the extremities and trunk and
      particularly from the gluteal region and medial parts of proximal thighs. Both
      types had similar excess of fat deposition in the neck, face, intraabdominal, and
      intermuscular regions. Women with atypical FPLD tended to have lower serum
      triglyceride and higher high density lipoprotein cholesterol concentrations. As
      exon 11 of LMNA does not comprise part of the lamin C-coding region, the R582H
      mutation affects only lamin A protein. Therefore, a unique phenotype of atypical
      FPLD may result from disrupted interaction of lamin A with other proteins and
      chromatin compared with typical FPLD, in which interaction of both lamins A and C
      may be disrupted.

PMID- 11231980
TI  - Glucose intolerance in obese adolescents with polycystic ovary syndrome: roles of
      insulin resistance and beta-cell dysfunction and risk of cardiovascular disease.
AB  - The roles of insulin resistance and insulin secretion in the pathogenesis of
      glucose intolerance in polycystic ovary syndrome (PCOS) were evaluated in 11
      adolescents with impaired glucose tolerance (IGT) and 10 with normal glucose
      tolerance (NGT). Hepatic glucose production and insulin-stimulated glucose
      disposal were measured using [6,6-(2)H(2)]glucose and a 3-h hyperinsulinemic (80
      mu/m(2).min)-euglycemic clamp. First and second phase insulin secretions were
      evaluated during a hyperglycemic clamp. Automated blood pressure measurements
      were made to assess the nocturnal change in blood pressure. Hepatic glucose
      production was significantly higher in IGT vs. NGT. Insulin-stimulated glucose
      disposal was not different between the two groups. The first phase insulin level
      was lower in IGT (207.9 +/- 21.0 vs. 357.0 +/- 62.9 muu/mL; P = 0.025; 1247 +/-
      126 vs. 2142 +/- 377 pmol/L) without a difference in second phase insulin. The
      glucose disposition index (product of insulin sensitivity x first phase insulin)
      was lower in IGT vs. NGT (278 +/- 40 vs. 567 +/- 119 mg/kg.min; P = 0.023; 1546
      +/- 223 vs. 3249 +/- 663 micromol/kg.min). The glucose disposition index
      correlated inversely with OGTT glucose concentrations at 30, 60, and 120 min.
      Adolescents with PCOS-IGT lacked the normal nocturnal decline in blood pressure.
      We conclude that in obese adolescents with PCOS, glucose intolerance is
      associated with 1) decreased first phase insulin secretion, 2) decreased glucose
      disposition index, and 3) increased hepatic glucose production. These metabolic
      abnormalities are precursors of type 2 diabetes and are present early in the
      course of PCOS. Furthermore, the absence of nocturnal dipping in blood pressure
      may herald the early expression of cardiovascular disease risk in these
      adolescents.

PMID- 11231981
TI  - Disruption of the joint synchrony of luteinizing hormone, testosterone, and
      androstenedione secretion in adolescents with polycystic ovarian syndrome.
AB  - The present study explores the postulate that the polycystic ovarian syndrome
      (PCOS) is marked by failure of physiological feedforward and feedback signaling
      between pituitary LH and ovarian androgens. To this end, we appraised the 3-fold
      simultaneous overnight release of LH (assayed by high precision
      immunofluorometry), testosterone (RIA), and androstenedione (RIA) in 12 an- or
      oligoovulatory adolescents with PCOS (mean +/- SEM age, 16.4 +/- 0.47 yr) and 10
      eumenorrheic girls (age, 16.5 +/- 0.45 yr). Gynecological (postmenarchal) ages
      (years) were also comparable at 4.8 +/- 0.39 (PCOS) and 4.0 +/- 3.6 (control; P =
      NS). Body mass index and fasting serum insulin and estradiol concentrations were
      indistinguishable in the two study cohorts. Mean overnight serum concentrations
      of LH (assayed by both immunofluorometry and Leydig cell bioassay), testosterone,
      androstenedione, and 17alpha-hydroxyprogesterone were each elevated significantly
      in patients with PCOS (all P </= 0.027). The bivariate cross-approximate entropy
      (cross-ApEn) statistic was used as a sensitive barometer of altered within-axis
      feedback. This scale-invariant metric is designed to quantitate the joint
      synchrony of putatively linked (neurohormone) time series in a lag-independent
      pattern-sensitive manner. Here, we applied cross-ApEn to the coupled release of
      LH and testosterone, LH and androstenedione, and testosterone and
      androstenedione. Statistical comparisons of the two adolescent study cohorts
      unveiled consistently elevated cross-ApEn in patients with PCOS, denoting
      disruption of the pairwise synchrony of LH and testosterone (P = 0.0055), LH and
      androstenedione (P = 0.0076), and testosterone and androstenedione (P = 0.014)
      secretion. As an analytically distinct technique to monitor coordinate hormone
      release, we also applied cross-correlation analysis with variable lag. This
      appraisal revealed that adolescents with PCOS further exhibit 1) loss of rapid
      feedforward coupling between LH and testosterone output, 2) erosion of the time
      lagged positive linkages between LH and androstenedione secretion, and 3)
      attenuation of the coordinate relationship between testosterone and
      androstenedione release. In summary, based on complementary, but independent,
      statistical tools, the present two-variable analyses unmask vivid deterioration
      of the joint synchrony of LH-testosterone, LH-androstenedione, and testosterone
      androstenedione secretion in adolescents with PCOS. The multiplicity of the
      bihormonal coupling defects points to impaired feedforward and feedback signaling
      interfaces among the hypothalamus, pituitary gland, and ovary. Disruption of
      interandrogen synchrony also identifies pathophysiological dissociation of
      testosterone and androstenedione cosecretion. Whether presumptive failure of
      integrative hypothalamo-pituitary-gonadal control emerges prepubertally in girls
      at risk for PCOS or persists in adults with PCOS is not known.

PMID- 11231982
TI  - Developmentally delimited emergence of more orderly luteinizing hormone and
      testosterone secretion during late prepuberty in boys.
AB  - To quantitate changing feedback control in the GnRH-LH/FSH-testosterone axis in
      male puberty, we here quantitate the orderliness of hormone release patterns
      using the regularity (pattern-sensitive) statistic, approximate entropy (ApEn),
      in 46 eugonadal boys representing 6 genitally defined stages of normal puberty.
      ApEn is a single variable, model-free, and scale-independent barometer of
      coordinate signaling or integrative regulation within a coupled neuroendocrine
      axis. Accordingly, we quantitated ApEn of LH profiles obtained by
      immunofluorometric assay of sera sampled every 20 min for 24 h. LH ApEn declined
      remarkably between early prepuberty (genital stage I-A: mean bone age, 4.6 +/-
      1.6 yr; testis volume, <3 mL for at least 3 succeeding yr) and late prepuberty
      (genital stage I-C: bone age, 8.7 +/- 1.8 yr; testis volume, <3 mL for up to 1 yr
      thereafter; P: = 0.00019), which indicates the acquisition of more regular LH
      release patterns in late prepuberty. Maximal LH orderliness occurred in puberty
      stage II (bone age, 10.7 +/- 1.0 yr; testis volume, 2.8 +/- 0.4 mL). The LH
      secretory process was more disorderly in mid- and later puberty (Tanner stages
      III and IV). Transpubertal variations in testosterone ApEn manifested a similar
      tempo, i.e. the greatest regularity of testosterone secretion (lowest ApEn)
      emerged in Tanner genital stage II (P: < 10(-)(7)), with less orderly patterns
      evident both earlier and later in sexual development. In contrast, FSH ApEn
      values remained invariant of pubertal status. Analysis of bihormonal coupling
      using the theoretically related bivariate cross-ApEn statistic disclosed maximal
      2-hormone synchrony for LH and testosterone secretion in genital stage II (P: =
      0.031), with relative deterioration of coordinate LH and testosterone release
      patterns both before and after. LH and FSH release became maximally synchronous
      at the end of prepuberty (genital stage I-C; P: = 0.029), and FSH and
      testosterone synchrony peaked in pubertal stage III (P: = 0.037). As mean 24-h
      serum concentrations of LH, FSH, and testosterone rose transpubertally by 35-fold
      (LH), 68-fold (FSH), and 70-fold (testosterone), respectively, we infer that
      pubertal developmental stage per se rather than level of hormone output dictates
      coordinate GnRH-LH/FSH-testosterone secretion. In summary, in eugonadal boys, the
      regularity of 24-h LH and testosterone secretory patterns undergoes well defined
      pubertal stage-specific control. No sexually developmentally delimited regulation
      is inferable for FSH. The concept of temporally biphasic puberty-dependent
      variations in neurohormone secretory regularity contrasts with the unidirectional
      rise in daily hormone output. Accordingly, we infer that late prepuberty and
      early puberty (Tanner genital stages IC and II) embody a physiologically unique
      sexual developmental window, marked by transiently enhanced LH and testosterone
      feedback stability in boys. Whether analogous plasticity of hypothalamo-pituitary
      gonadal interactions unfolds during female adolescence is not known.

PMID- 11231983
TI  - Temporal patterns of circulating leptin levels in lean and obese adolescents:
      relationships to insulin, growth hormone, and free fatty acids rhythmicity.
AB  - Alterations in nutritional status, such as obesity, markedly influence insulin,
      leptin, GH secretion, and free fatty acid (FFA) levels. We measured every hour
      for 24 h circulating leptin, insulin, GH, and FFA levels in lean and obese
      adolescents to determine: 1) the impact of adolescent obesity on the diurnal
      changes in leptin concentrations; and 2) the temporal relationships between the
      diurnal patterns of circulating leptin levels and insulin, GH, and FFA levels.
      During puberty, we found that the 24-h profile of circulating plasma leptin
      levels follows a bimodal pattern with minimal concentrations occurring early in
      the afternoon and a nocturnal elevation starting after midnight and culminating
      early morning. The time course of the diurnal variation in leptin levels in the
      obese adolescents was not different from that in lean controls. Of note, however,
      in obese girls leptin 24-h excursion and leptin night to day ratio were lower
      than those found in lean girls. In obese adolescents, mean GH levels varied
      significantly less during the day and night than lean controls. During the day,
      there were distinct preprandial increases and postprandial decreases in FFA
      levels, whereas after midnight FFA levels rose in both lean and obese
      adolescents. A significant positive correlation was found between mean plasma
      insulin levels between 0800 h and 2000 h and peak in leptin in lean and obese
      girls and boys (r = 0.63, P: < 0.001). Peak leptin was inversely correlated with
      the area under the nocturnal GH levels in all groups (r = -0.31, P: < 0.0003),
      whereas it was positively correlated with the nocturnal peak in FFA levels (r =
      0.45, P: < 0.004). In summary, we report in obese adolescent girls a blunted
      relative diurnal excursion in leptin levels. This abnormal rhythmicity may, in
      part, explain their leptin resistance state. The nocturnal rise in leptin was
      paralleled by a nocturnal rise in GH and FFA levels. Additional studies are
      needed to test the potential link between the adipose-derived peptide and GH axis
      in humans.

PMID- 11231985
TI  - Fetal hypothalamic-pituitary-adrenal stress responses to invasive procedures are
      independent of maternal responses.
AB  - Paired fetal and maternal samples were obtained, at fetal blood sampling and
      intrauterine transfusion, to study hypothalamic-pituitary-adrenal stress
      responses. This confirmed that the fetus mounts an hypothalamic-pituitary-adrenal
      stress response to transfusion via the intrahepatic vein, which involves piercing
      the fetal trunk, but not to transfusion via the placental cord insertion [mean
      cortisol response via intrahepatic vein delta = 52.6 nmol/L, 95% CI (25.3-79.9),
      P = 0.001; mean beta-endorphin response delta =106 pg/mL, 95% CI (45.3-167), P =
      0.002]. Baseline maternal fetal ratios were 13 [95% CI (10.7-15.2)] for cortisol
      and 0.8 [95% CI (0.5-1.0)] for beta-endorphin. The novel findings were: 1) that
      the fetal responses were independent of those of the mother, which did not change
      during transfusion at either site; 2) that there was a correlation between
      baseline fetal and maternal cortisol levels (r = 0.58, n = 51, P < 0.0001) but
      not between baseline fetal and maternal ss-endorphin levels, suggesting cortisol
      transfer across the placenta, rather than joint control by placental CRH; and 3)
      that fetal beta-endorphin responses were apparent from 18 weeks gestation and
      independent of gestational age, whereas fetal cortisol responses were apparent
      from 20 weeks gestation and were dependent on gestational age (y = -91.4 + 5.08x,
      r = 0.51; n = 16; P = 0.04; CI for slope, 0.16-10.0), consistent with the
      maturation of the fetal pituitary before the fetal adrenal.

PMID- 11231984
TI  - Racial disparities in metabolism, central obesity, and sex hormone-binding
      globulin in postmenopausal women.
AB  - Increased total and intraabdominal fat (IAF) obesity as well as other metabolic
      conditions associated with the insulin resistance syndrome (IRS) are related to
      low levels of sex hormone-binding globulin (SHBG) in young and older Caucasian
      (CAU) and young African-American (AA) women. We examined whether postmenopausal
      AA women, a population with a high incidence of obesity and IRS despite low IAF,
      would have higher levels of circulating SHBG compared with CAU women, and whether
      there would be negative relationships between indexes of obesity and risk factors
      associated with IRS and SHBG levels. We measured body composition, SHBG, free
      testosterone, leptin, glucose tolerance, insulin, and lipoprotein lipids in 55
      CAU (mean +/- SD, 59 +/- 7 yr) and 35 AA (57 +/- 6 yr) sedentary women of
      comparable obesity (48% body fat, by dual energy x-ray absorptiometry). Compared
      with CAU women, AA women had larger waist (101 vs. 96 cm), larger fat mass (44.9
      +/- 8.8 vs. 39.9 +/- 8.1 kg), larger sc fat area (552 +/- 109 vs. 452 +/- 109
      cm(2)), and lower IAF/SC ratio (0.28 +/- 0.12 vs. 0.38 +/- 0.15; P < 0.01), but
      similar waist to hip ratio (0.83). Both groups had similar SHBG (117 vs. 124
      nmol/L) and free testosterone (3.7 vs. 3.4 pmol/L) levels, but AA women had a 35%
      higher leptin, 34% higher fasting insulin, and 39% greater insulin response to a
      glucose load (P < 0.05) compared with CAU women. In CAU, but not AA, women SHBG
      correlated negatively with body mass index (r = -0.28; P < 0.05), waist (r = 
      0.36; P = 0.01), IAF (r = -0.34; P = 0.01), and insulin response to oral glucose
      (r = -0.37; P < 0.05) and positively with high density lipoprotein cholesterol (r
      = 0.30; P = 0.03). The relationship between insulin area and SHBG in CAU women
      disappeared after adjusting for IAF, whereas the relationship between high
      density lipoprotein cholesterol and SHBG persisted after adjusting for IAF, but
      not for fat mass. Leptin was positively related to fat mass (P < 0.05) in both
      groups, but it was related to insulin only in the Caucasian women (P< 0.01).
      There was a racial difference in the slopes (P< 0.05) of the relationships of
      leptin to fat mass (P < 0.05). Racial differences in leptin disappeared after
      adjustment for fasting insulin. These results suggest that the metabolic
      relationships between total and regional obesity, glucose, and lipid metabolism
      with SHBG in CAU women are different from those in postmenopausal obese AA women.

PMID- 11231987
TI  - Incidence and late prognosis of cushing's syndrome: a population-based study.
AB  - The main purpose was to assess the incidence and late outcome of Cushing's
      syndrome, particularly in Cushing's disease. Information for all patients
      diagnosed with Cushing's syndrome during an 11-yr period in Denmark was
      retrieved. The incidence was 1.2-1.7/million.yr (Cushing's disease),
      0.6/million.yr (adrenal adenoma) and 0.2/million.yr (adrenal carcinoma). Other
      types of Cushing's syndrome were rare. In 139 patients with nonmalignant disease,
      11.1% had died during follow-up (median, 8.1 yr; range, 3.1-14.0), yielding a
      standard mortality ratio (SMR) of 3.68 [95% confidence interval (CI), 2.34-5.33].
      The SMR was partly attributable to an increased mortality within the first year
      after diagnosis. Eight patients died before treatment could be undertaken. The
      prognosis in patients with malignant disease was very poor. Patients in whom more
      than 5 yr had elapsed since initial surgery were studied separately, including a
      questionnaire on their perceived quality of health. In 45 patients with Cushing's
      disease who had been cured through transsphenoidal neurosurgery, only 1 had died
      (SMR, 0.31; CI, 0.01-1.72) compared with 6 of 20 patients with persistent
      hypercortisolism after initial neurosurgery (SMR, 5.06; CI, 1.86-11.0). In
      patients with adrenal adenoma, SMR was 3.95 (CI, 0.81-11.5). The perceived
      quality of health was significantly impaired only in patients with Cushing's
      disease and appeared independent of disease control or presence of
      hypopituitarism. It is concluded that 1) Cushing's syndrome is rare and is
      associated with increased mortality, in patients with no concurrent malignancy
      also; 2) the excess mortality was mainly observed during the first year of
      disease; and 3) the impaired quality of health in long-term survivors of
      Cushing's disease is not fully explained.

PMID- 11231986
TI  - Impairment in cognitive and exercise performance during prolonged antarctic
      residence: effect of thyroxine supplementation in the polar triiodothyronine
      syndrome.
AB  - Humans who work in Antarctica display deficits in cognition, disturbances in
      mood, increased energy requirements, a decline of thyroid hormone products, and
      an increase of serum TSH. We compared measurements in 12 subjects, before
      deployment (baseline), with 11 monthly studies during Antarctic residence (AR).
      After 4 months of AR (period 1), half of the subjects (T(4) group) received L
      thyroxine [64 nmol.day(-)(1) (0.05 mg.day(-)(1))]; and the other half, a placebo
      (placebo group) for the next 7 months of AR (period 2). During period 1, there
      was a 12.3 +/- 5.1% (P < 0.03) decline on the matching-to-sample (M-t-S)
      cognitive task and an increase in depressive symptoms, compared with baseline.
      During the intervention in period 2, M-t-S scores for the T(4)-treated group
      returned to baseline values; whereas the placebo group, in contrast, showed a
      reduced M-t-S score (11.2 +/- 1.3%; P < 0.0003) and serum free T(4) (5.9 +/-
      2.4%; P < 0.02), compared with baseline. The change in M-t-S score was correlated
      with the change in free T(4) (P < 0.0003) during both periods, and increases in
      serum TSH preceded worsening scores in depression, tension, anger, lack of vigor,
      and total mood disturbance (P < 0.001) during period 2. Additionally, the
      submaximal work rate for a fixed O(2) use decreased 22.5 +/- 4.9% in period 1 and
      remained below baseline in period 2 (25.2 +/- 2.3%; P < 0.005) for both groups.
      After 4 months of AR, the L-thyroxine supplement was associated with improved
      cognition, which seems related to circulating T(4). Submaximal exercise
      performance decrements, observed during AR, were not changed with this L
      thyroxine dose.

PMID- 11231988
TI  - Effects of free fatty acids on insulin sensitivity and hemodynamics during mental
      stress.
AB  - Mental stress is known to decrease systemic vascular resistance and increase
      muscle blood flow and to acutely enhance insulin-mediated glucose disposal in
      healthy humans. These effects are abolished in obese patients. We therefore
      proposed the hypothesis that elevated free fatty acid levels may be responsible
      for the abnormal responses to mental stress in obesity by inhibiting endothelial
      cell function. To test this hypothesis, we studied a group of eight lean females
      during a hyperinsulinemic clamp study with and without lipid infusion. A 30-min
      mental stress was applied during 30 min after 150 min of hyperinsulinemia. In the
      study without lipid infusion, mental stress increased heart rate by 26.5%, blood
      pressure by 7.9%, and cardiac index (measured with thoracic bioimpedance) by
      35.9%; it decreased systemic vascular resistance by 21.9% and increased insulin
      mediated glucose disposal by 18.9%. During lipid infusion, the increase in heart
      rate was not affected, but the increase in cardiac index, the decrease in
      systemic vascular resistance, and the increase in insulin-mediated glucose
      disposal were all inhibited. In contrast, the rise in blood pressure was
      increased about 2-fold (control plus 6 mm Hg vs. lipid plus 13 mm Hg, P: < 0.01).
      These results indicate that lipid inhibits the stimulation of glucose uptake and
      enhances the pressor effect of mental stress, presumably by altering endothelial
      cell function.

PMID- 11231989
TI  - Diminished melatonin secretion in the elderly caused by insufficient
      environmental illumination.
AB  - The pineal hormone melatonin has some circadian regulatory effects and is assumed
      to have a close relation with sleep initiation and maintenance. Many previous
      reports have described age-related decreases in melatonin levels, especially in
      elderly insomniacs (EIs), which may act as causal or exacerbating factors in
      sleep disturbances in the elderly. Ten elderly residents with psychophysiological
      insomnia (mean age, 74.2 yr), 10 healthy residents of the same home [elderly
      control (EC) group; mean age, 72.7 yr], and 10 healthy young control subjects
      (mean age, 20.9 yr) living at home participated in this study. The elderly
      persons, especially the EIs, were exposed to significantly less environmental
      light and simultaneously suffered from significantly diminished nocturnal
      melatonin secretion. Supplementary exposure to 4 h (1000 to 1200 h, 1400 to 1600
      h) of midday bright light in the EI group significantly increased melatonin
      secretion to levels similar to those in the young control group without circadian
      phase-shifting. There was a tendency for the magnitude of the increase in
      nocturnal melatonin secretion stimulated by bright light to parallel amelioration
      of sleep disturbances in these subjects. The present findings suggest that we
      need to pay attention to elderly individuals who suffer under conditions of poor
      environmental light resulting in disorganized circadian rhythms, including the
      sleep-wake cycle.

PMID- 11231990
TI  - Association between estrogen receptor-beta gene polymorphisms and ovulatory
      dysfunctions in patients with menstrual disorders.
AB  - Estrogen plays a significant role in human ovulation. It acts as an important
      positive regulator of the preovulatory gonadotropin surge necessary to initiate
      the cascade of events leading to ovulation. The steroid hormone exerts its
      physiological responses through the estrogen receptor (ER), of which two
      subtypes, ERalpha and ERbeta, are known. ERbeta messenger ribonucleic acid occurs
      maximally in the ovaries and granulosa cells; thus, ERbeta may be essential for
      normal ovulation. In a recent gene knockout study, it has been shown that ERbeta
      gene null female mice develop normal reproductive tract and ovaries during pre-
      and neonatal periods, but have an abnormal frequency of spontaneous ovulation in
      adulthood. In the present case-control study, we explored the association of two
      recently described ERbeta gene polymorphisms, RSAI and ALUI, with ovulatory
      dysfunctions. The respective frequencies of these polymorphisms were
      significantly higher in patients than in controls (P= 0.009 and P= 0.059). The
      polymorphisms were significantly associated with ovulatory dysfunctions,
      especially in patients homozygous for the polymorphisms (P = 0.016 and P = 0.038,
      respectively). The compound homozygosity of the polymorphisms was seen only in
      patients (n = 5) and not controls (P = 0.009). The serum levels of LH, FSH, and
      progesterone were lower in the homozygous and compound homozygous than in the
      respective nonpolymorphic patients. All five compound homozygous patients had
      ovulatory dysfunctions with no etiological pathology. Our results suggest that
      ERbeta gene RSA:I and ALU:I polymorphisms may be associated with ovulatory
      defects in some patients, especially those with unknown causes.

PMID- 11231991
TI  - Bim-23244, a somatostatin receptor subtype 2- and 5-selective analog with
      enhanced efficacy in suppressing growth hormone (GH) from octreotide-resistant
      human GH-secreting adenomas.
AB  - Although both somatostatin receptor subtype 2 (SSTR2) and SSTR5 messenger
      ribonucleic acid (mRNA) are consistently expressed in GH-secreting adenomas,
      SSTR2 has been believed to be the key modulator of somatostatin-mediated
      inhibition of GH release. The somatostatin agonists currently in clinical use,
      octreotide and lanreotide, are directed mainly to SSTR2 (IC(50) 12- to 18-fold
      higher than for SSTR5). Recently, however, it was demonstrated that an SSTR5
      preferential agonist, BIM-23268, not only suppressed PRL release from
      prolactinomas and mixed GH-PRL adenomas, but also inhibited GH release in about
      half of GH adenomas. In addition, the SSTR5-preferring analog showed a slight
      additive effect when used in combination with SSTR2 preferential drugs at
      submaximal concentrations in octreotide partially sensitive adenomas. In the
      present study we quantified SSTR2 and SSTR5 mRNA expression and the GH
      suppressive effects of somatostatin-14; octreotide; a SSTR2-preferential
      compound, BIM-23197; a SSTR5-preferential compound, BIM-23268; and a new SSTR2-
      and SSTR5-bispecific compound, BIM-23244, in GH-secreting tumors classified as
      either full responders to octreotide (n = 5) or partially sensitive to octreotide
      (n = 5). The octreotide-sensitive GH secretory adenomas presented with a high
      level of both SSTR2 and SSTR5 mRNA expression [222 +/- 61 and 327 +/- 136 pg/pg
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH), respectively]. In these tumors
      the suppression of GH release was similarly achieved at picomolar ranges by
      octreotide, BIM-23197, and BIM-23244 (EC(50) = 25 +/- 15, 3 +/- 2, and 3 +/- 3
      pmol/L, respectively). The compounds preferential for only SSTR5 were unable to
      inhibit GH release in such tumors. Among the octreotide partially responsive
      tumors, SSTR2 mRNA expression was 9-fold lower than in the octreotide-sensitive
      tumors (25 +/- 12 vs. 222 +/- 61 pg/pg GAPDH; P < 0.015), whereas SSTR5 mRNA
      expression was approximately 7-fold higher than in the octreotide-sensitive
      tumors (2271 +/- 1197 pg/pg GAPDH). In these octreotide partially responsive
      tumors, the SSTR5-preferential compound, BIM-23268, and the SSTR2- and SSTR5
      bispecific compound, BIM-23244, were quite effective in suppressing GH secretion
      (EC(50) = 25 +/- 13 and 50 +/- 31 pmol/L, respectively). Similarly, BIM-23244,
      was able to suppress by 51 +/- 5% PRL release from five mixed GH- and PRL
      secreting adenomas. These data indicate that due to heterogeneous expression of
      SSTR2 and SSTR5 receptor subtypes, in GH-secreting tumors, a bispecific analog,
      such as BIM-23244, that can activate both receptors could achieve better control
      of GH hypersecretion in a larger number of acromegalic patients.

PMID- 11231992
TI  - Urinary nandrolone metabolites of endogenous origin in man: a confirmation by
      output regulation under human chorionic gonadotropin stimulation.
AB  - 19-Nortestosterone (nandrolone) is an anabolic steroid compound widely used as a
      doping agent by athletes. The analysis of its urinary metabolites, 19
      norandrosterone (NA) and 19-noretiocholanolone (NE) glucuronides, allows the
      detection of surreptitious administration of nandrolone in sport. A threshold
      concentration at 2 microgram/L urinary nandrolone metabolites is advocated by the
      International Olympic Committee for the detection of doping, but some controversy
      concerning the validity of this threshold arose from the demonstration of
      endogenous production of nandrolone in mammals, including humans. The regulation
      of human nandrolone production and its contribution in vivo to the process of
      aromatization remain unknown. In the present study 10 healthy men were
      successively submitted to insulinic stress and gonadal stimulation by hCG
      administration. Urinary NA and NE concentrations were quantified by gas
      chromatography-mass spectrometry. NA was detected in basal urine samples from all
      subjects, with a mean urinary excretion rate (UER) of 3.17 +/- 0.35 ng/h, whereas
      NE was detected in 4 of 10 (UER range, 0.8-4.7 ng/h). Insulinic hypoglycemia did
      not significantly modify mean NA UER despite random intraindividual variations
      between timed urine collections. After hCG administration, NA UER increased by
      250% (P < 0.01) and estradiol (E(2)) UER by 260% (P < 0.001). The maximum NA
      concentration obtained after stimulation was 0.43 microgram/L. NA UER, plasma
      E(2), and E(2)/T ratio peaked on day 1 after hCG administration, whereas plasma T
      peaked later on day 3. NA UER correlated with plasma E(2) (r = 0.61; P < 0.001)
      and E(2)/T (r = 0.51; P < 0.001), but not with plasma T. In conclusion, insulinic
      stress did not significantly alter nandrolone metabolism, whereas the effect of
      hCG was a stimulation of NA excretion in all subjects, which constitutes strong
      support for the endogenous origin of low basal NA excretion. The comparative
      kinetics of NA UER, plasma E(2), and E(2)/T ratio suggest a contribution of the
      aromatase process to nandrolone biosynthesis in man.

PMID- 11231993
TI  - Transition from dim to bright light in the morning induces an immediate elevation
      of cortisol levels.
AB  - The only well documented effect of light exposure on endocrine function is the
      suppression of nocturnal melatonin. Bright light exposure has behavioral effects,
      including the alleviation of sleepiness during nocturnal sleep deprivation. The
      present study examines the effects of bright light on the profiles of hormones
      known to be affected by sleep deprivation (TSH) or involved in behavioral
      activation (cortisol). Eight healthy men participated each in three studies
      involving 36 h of continuous wakefulness. In one study, the subjects were exposed
      to constant dim light (baseline). In the two other studies, dim light exposure
      was interrupted by a 3-h period of bright light exposure either from 0500-0800 h
      (early morning study) or from 1300-1600 h (afternoon study). Blood samples were
      obtained every 15 min for 24 h to determine melatonin, cortisol, and TSH
      concentrations. Alertness was estimated by the number of lapses on two
      computerized vigilance-sensitive performance tasks. The early morning transition
      from dim to bright light suppressed melatonin secretion, induced an immediate,
      greater than 50% elevation of cortisol levels, and limited the deterioration of
      alertness normally associated with overnight sleep deprivation. No effect was
      detected on TSH profiles. Afternoon exposure to bright light did not have any
      effect on either hormonal or behavioral parameters. The data unambiguously
      demonstrate an effect of light on the corticotropic axis that is dependent on
      time of day.

PMID- 11231994
TI  - Evidence that parenteral testosterone therapy may improve endothelium-dependent
      and -independent vasodilation in postmenopausal women already receiving estrogen.
AB  - The gender difference in cardiovascular disease has been partly attributed to
      higher androgenic hormone levels. Although testosterone in women may not affect
      lipids, it remains unknown whether it negates favorable estrogenic effects on
      endothelial function. We have investigated the effects of testosterone implant
      therapy on arterial reactivity encompassing endothelial-dependent and 
      independent vasodilation in women using hormone replacement therapy (HRT). B-mode
      ultrasound measurements of resting brachial artery diameter, following reactive
      hyperemia [endothelium-dependent flow- mediated dilation (FMD)] and following
      glyceryl trinitrate (GTN) (endothelium-independent dilation), were recorded in 33
      postmenopausal women stabilized on HRT (>6 months), at baseline, and 6 weeks
      after a testosterone implant (50 mg), with 15 postmenopausal nonusers of HRT
      serving as controls. In the brachial artery, baseline resting diameter was
      similar (0.40 +/- 0.01 vs. 0.41 +/- 0.01 cm, P = 0.5). In the treated group,
      testosterone levels increased (0.99 +/- 0.08 to 4.99 +/- 0.3 nmol/L, P < 0.001),
      associated with a mean 42% increase in FMD (6.4% +/- 0.7 to 9.1% +/- 1.1, P =
      0.03). The control group did not change (8.1% +/- 1.4 to 5.6% +/- 1.0, P = 0.4).
      ANOVA of repeated measures (P = 0.04) and mean change (P = 0.02) in FMD both
      demonstrated significantly greater improvement with testosterone compared with
      controls. GTN induced vasodilation increased with testosterone treatment (14.9%
      +/- 0.9 to 17.8% +/- 1.2, P = 0.03). Our preliminary data indicate that
      parenteral testosterone therapy improves both endothelial-dependent (flow
      mediated) and endothelium-independent (GTN-mediated) brachial artery vasodilation
      in postmenopausal women using long-term estrogen therapy. The mechanisms
      underlying these potentially beneficial cardiovascular effects require further
      investigation.

PMID- 11231995
TI  - Weight loss is not associated with hyperleptinemia in humans with pancreatic
      cancer.
AB  - Pathological weight loss is a feature of many diseases and contributes to
      mortality and morbidity. Although cytokines have been implicated in some models
      of pathological weight loss, little is known about cellular mechanisms
      responsible for cachexia in patients with cancer. Leptin is a fat cell product
      that acts centrally to reduce appetite and decrease metabolism. Leptin synthesis
      is stimulated by cytokines, and circulating levels of cytokines are elevated in
      some cancer patients. We hypothesized that cytokine-induced hyperleptinemia
      contributes to pathological weight loss in patients with pancreatic cancer. To
      evaluate this hypothesis, fasting serum leptin concentrations were measured in 64
      patients undergoing surgery for pancreatic cancer. Preoperative interviews were
      used to assess body weight and appetite history. Thirty of 64 pancreatic cancer
      patients had cachexia (weight loss of >10% over the 6 months before surgery).
      Self-reported loss of appetite was associated with the presence of cachexia.
      Leptin concentrations, when corrected for body mass index, were lower than levels
      reported in healthy humans. Six patients had leptin levels more than 2 times
      those predicted by body mass index. There was no association between patients
      with increased leptin concentration and weight loss or anorexia. We conclude that
      a reduced appetite contributes to weight loss in patients with pancreatic cancer.
      High plasma leptin levels, however, do not appear to contribute to cachexia in
      these patients.

PMID- 11231996
TI  - Effects of recombinant human insulin-like growth factor I administration on the
      growth hormone (gh) response to GH-releasing hormone in obesity.
AB  - Circulating GH levels are reduced in obesity due to true reduction of the 24-h GH
      production rate. GH insufficiency in obesity might reflect neuroendocrine
      abnormalities and/or alterations in peripheral hormones and metabolic factors.
      The somatotroph response to provocative stimuli including GHRH is markedly
      blunted in obese patients. However, the somatotroph responsiveness to GHRH in
      obesity shows also peculiar refractoriness to the inhibitory effect of glucose
      load. In this present study we aimed at verifying the effect of low dose rhIGF-I
      (20 microgram/kg, sc, at 0 min) on the GH response to GHRH (1 microgram/kg, iv,
      at 180 min) in obesity. With this goal in mind, six obese women with abdominal
      adiposity [OB; age (mean +/- SEM), 32.3 +/- 4.4 yr; body mass index, 32.8 +/- 2.3
      kg/m(2)] were studied. The effects of recombinant human insulin-like growth
      factor I (rhIGF-I) administration on circulating total IGF-I, insulin, and
      glucose levels were also evaluated. The results in OB were compared with those
      recorded in age-matched lean women (NW; age, 28.3 +/- 1.2 yr; body mass index,
      20.1 +/- 0.5 kg/m(2)), in whom the inhibitory effect of rhIGF-I had already been
      shown. Basal IGF-I levels in OB were similar to those in NW (199.7 +/- 33.3 vs.
      274.4 +/- 25.3 microgram/L). The mean GH concentration over 3 h (from 0-180 min)
      in OB was lower than that in NW (0.9 +/- 0.4 vs. 2.6 +/- 0.8 microgram/L; P =
      NS). Administration of GHRH induced a GH response in OB lower than that in NW
      (area under the curve from 180-270 min, 576.5 +/- 137.5 vs. 1315.9 +/- 189.9
      microgram/L.min; P < 0.02). Administration of rhIGF-I increased circulating IGF-I
      levels in both groups to the same percent extent (326.8 +/- 28.3 and 420.3 +/-
      26.5 microgram/L in OB and NW, respectively). rhIGF-I administration inhibited
      the GH response to GHRH in OB (240.1 +/- 99.6 microgram/L; P < 0.05) as well as
      in NW (730.2 +/- 288.1 microgram/L; P < 0.05), although it failed to lower the
      mean GH concentration over 3 h in either OB or NW. After rhIGF-I the GH response
      to GHRH in OB was slight and was still lower (P < 0.05) than that in NW; in fact,
      the percent decreases were similar in both groups (44.21 +/- 14.06 and 48.21 +/-
      13.95 microgram/L, in OB and NW, respectively). The mean insulin (107.1 +/- 21.9
      and 36.8 +/- 7.2 pmol/L), but not glucose (4.0 +/- 0.3 and 4.1 +/- 0.1 mmol/L),
      levels calculated over 270 min, were higher (P = 0.005) in OB than in NW; rhIGF-I
      administration did not modify insulin and glucose levels in either group. Our
      study shows that the sc administration of a low rhIGF-I dose inhibits the
      somatotroph responsiveness to GHRH in obese as well as in normal subjects,
      indicating that somatotroph sensitivity to the inhibitory effect of rhIGF-I is
      preserved in obesity.

PMID- 11231997
TI  - Relationship between angiotensin-converting enzyme gene polymorphism and insulin
      resistance in never-treated hypertensive patients.
AB  - The association between angiotensin-converting enzyme (ACE) gene polymorphism and
      insulin resistance (IR) in hypertensive subjects remains controversial. Thus, we
      evaluated the possible association between IR and ACE gene polymorphism in a
      group of hypertensive, never-treated patients compared with that in a
      normotensive control group. We enrolled 200 (114 men and 86 women; age, 45.5 +/-
      4.7 yr) hypertensive patients and 96 (54 men and 42 women; age, 44.0 +/- 4.7 yr)
      normotensive subjects. A double PCR assay was used to identify ACE genotypes. We
      determined fasting glucose and insulin by the glucose oxidase method and using a
      standard RIA technique. IR was estimated using the homeostasis model assessment
      (HOMA(IR)). Both fasting glucose (5.0 +/- 0.3 vs. 4.7 +/- 0.3 mmol/L; P <
      0.0001), insulin levels (12.3 +/- 4.7 vs. 4.9 +/- 1.5 muU/mL; P < 0.0001), and
      HOMA(IR) (2.7 +/- 1.1 vs. 1.1 +/- 0.3; P < 0.0001) were significantly higher in
      hypertensive patients than in the normotensive control group. When we subdivided
      hypertensive patients according to ACE genotype, we observed that fasting insulin
      and HOMA(IR) were 16.3 +/- 3.3 and 3.6 +/- 0.8 in the DD genotype, 9.4 +/- 3.1
      and 2.1 +/- 0.7 in the ID genotype, and 8.3 +/- 2.8 and 1.9 +/- 0.7 muU/mL in the
      II group (P < 0.0001, by ANOVA). No significant differences were observed in the
      normotensive control group. In conclusion, we extended previous data regarding
      the relationship of hypertension and IR by demonstrating a dependence of this
      relationship upon the ACE gene polymorphism.

PMID- 11231998
TI  - Effects of contraceptive use on bone biochemical markers in young women.
AB  - The purpose of this study was to compare biochemical markers of bone resorption
      and formation in young women using different hormonal contraceptive methods.
      Women aged 18-39 yr who were using depot medroxyprogesterone acetate (DMPA)
      contraception were recruited for the study; comparison women were matched by age
      and clinic location. There were 116 women using DMPA, 39 using oral
      contraceptives containing estrogen and progestin, and 72 not currently using
      hormonal contraceptives. Biochemical measurements were serum calcium, PTH and
      osteocalcin, and urine N-telopeptide. Bone density was measured using dual-energy
      x-ray absorptiometry. The N-telopeptide levels, adjusted for age and other risk
      factors, were 42.4 +/- 2.3 nmol/mmol creatinine in the DMPA group, 26.2 +/- 3.3
      nmol/mmol in the oral contraceptive group, and 35.4 +/- 2.9 nmol/mmol in the
      nonusers; significant differences were seen in all pairwise comparisons.
      Osteocalcin levels showed the same pattern, although the difference between the
      DMPA users and nonusers was not statistically significant. There were no
      differences among groups in the PTH levels. The bone density at the spine was
      1.086 +/- 0.085 g/cm(2) in the DMPA group, 1.103 +/- 0.095 g/cm(2) in the oral
      contraceptive group, and 1.093 +/- 0.090 g/cm(2) in nonusers (P = 0.051). The
      results suggest that in women using DMPA bone resorption exceeded bone formation.

PMID- 11231999
TI  - Relationship of etiology to treatment in congenital hypothyroidism.
AB  - We examined the patterns of TSH, T(4), and treatment schedules from diagnosis to
      4 yr of age in 125 children (50 males anf 75 females) with congenital
      hypothyroidism (CH). Subjects were divided into 3 groups based on their thyroid
      scans: 1) athyreosis (n = 31), 2) dysgenesis (n = 54; 49 lingual and 5
      hypoplastic), and 3) dyshormonogenesis (n = 40). Follow-up evaluation was carried
      out at 2-4 wk and 3, 6, 9, 12, 24, 36, and 48 months of age. Median gestational
      age, age at onset of therapy, and starting L-T(4) dose were similar in the three
      groups. In infants with athyreosis median screening TSH levels were higher (P <
      0.02) and confirmatory T(4) levels were lower than in the other two groups (P <
      0.01 vs. dysgenetic; P < 0.05 vs. dyshormonogenetic CH). During the first 6
      months of therapy, mean TSH levels were highest in the athyrotic group,
      intermediate in the dysgenetic group, and lowest in the dyshormonogenetic group.
      In children with athyreosis, TSH levels normalized by 12 months of age. At 12
      months dysgenetic patients had the highest TSH levels (P < 0.05). During the
      entire study period, TSH levels were lowest in patients with dyshormonogenesis
      (except at 48 months) and normalized earlier. Mean T(4) levels normalized by 2-4
      weeks in all groups. At 3 and 6 months, the percentage of patients who required
      dose changes was highest in the athyrotic group, and at 12 months it was highest
      in the dysgenetic group. The athyrotic group received the highest dose of L-T(4),
      and dyshormonogenetic group received the lowest dose. We conclude that treatment
      and follow-up schedules for CH may differ in the three etiological categories
      based on the different hormonal patterns and responses to therapy. Children with
      athyreosis need close monitoring particularly early in life, whereas those with
      dysgenesis and dyshormonogenesis require more attention later in life.

PMID- 11232000
TI  - Bioavailable estradiol may be an important determinant of osteoporosis in men:
      the MINOS study.
AB  - During recent years, experimental data, case reports, and epidemiological studies
      have suggested an important role for estradiol in bone metabolism in men. In a
      cohort of 596 men, aged 51-85 yr, we measured bone mineral density (BMD) of the
      lumbar spine, hip, total body, and forearm; serum levels of sex steroid hormones
      [total and free testosterone, total estradiol (17betaE(2)), bioavailable
      estradiol (bio-17betaE(2)), androstenedione, and sex hormone-binding globulin];
      and markers of bone turnover [serum osteocalcin, bone alkaline phosphatase, N
      terminal extension propeptide of type I collagen, and beta-isomerized C-terminal
      telopeptide of collagen type I (betaCTX)], as well as urinary excretion of
      betaCTX and deoxypyridinoline (DPyr). An age-related decrease was found for bio
      17betaE(2) (r = -0.16; P < 0.001), free testosterone (r = -0.25; P < 0.001), free
      testosterone index (r = -0.32; P < 0.001), and androstenedione (r = -0.22; P <
      0.001), but not for total 17betaE(2) or total testosterone. 17betaE(2) and bio
      17betaE(2), but not other hormones, were correlated with BMD after adjustment for
      age and body weight. In men with a bio-17betaE(2) level in the lowest quartile,
      the average BMD was lower than in men having a bio-17betaE(2) level in the
      highest quartile by 6.6-8.7% according to the site of measurement, which
      corresponded to 0.45-0.65 SD. In age- and body weight-adjusted models, bio
      17betaE(2), but not other hormones, was negatively correlated with bone markers
      (e.g., osteocalcin: r = -0.14; P < 0.001; urinary betaCTX: r = -0.20; P = 0.0001;
      DPyr: r = -0.14; P < 0.001). In men with the lowest concentration of bio
      17betaE(2) (first quartile), the concentrations of markers of bone turnover were
      higher by 11-35% (or 0.4-0.7 SD) than in men having the highest bio-17betaE(2)
      level (upper quartile). In men in the lowest quartile for bio-17betaE(2) and in
      the highest quartile for urinary DPyr or betaCTX, the BMD of total hip and that
      of distal forearm were 8% and 10% lower than in men in the highest quartile for
      bio-17betaE(2) and in the lowest quartile for DPyr or ssCTX. In the age- and body
      weight-adjusted multiple regression models, bio-17betaE(2) contributed
      significantly to the explanation for the variability in all markers. In summary,
      we found in a cross-sectional analysis of a cohort of men that low levels of bio
      17betaE(2) are associated with high bone turnover and low BMD. These data suggest
      that the age-related decrease in bio-17betaE(2) contributes to bone loss in
      elderly men by increasing bone turnover. Low 17betaE(2) levels may be an
      important risk factor for osteoporosis in men.

PMID- 11232001
TI  - The response of molecular isoforms of growth hormone to acute exercise in trained
      adult males.
AB  - Circulating GH consists of multiple molecular isoforms, all derived from the one
      gene in nonpregnant humans. To assess the effect of a potent stimulus to
      pituitary secretion on GH isoforms, we studied 17 aerobically trained males (age,
      26.9 +/- 1.5 yr) in a randomized, repeat measures study of rest vs. exercise.
      Exercise consisted of continuous cycle ergometry at approximately 80% of
      predetermined maximal oxygen uptake for 20 min. Serum was assayed for total,
      pituitary, 22-kDa, recombinant, non-22-kDa, 20-kDa, and immunofunctional GH. All
      isoforms increased during, peaked at the end, and declined after exercise. At
      peak exercise, 22-kDa GH was the predominant isoform. After exercise, the ratios
      of non-22 kDa/total GH and 20-kDa GH/total GH increased and those of
      recombinant/pituitary GH decreased. The disappearance half-times for pituitary GH
      and 20-kDa GH were significantly longer than those for all other isoforms. We
      conclude that 1) all molecular isoforms of GH measured increased with and peaked
      at the end of acute exercise, with 22-kDa GH constituting the major isoform in
      serum during exercise; and 2) the proportion of non-22-kDa isoforms increased
      after exercise due in part to slower disappearance rates of 20-kDa and perhaps
      other non-22-kDa GH isoforms. It remains to be determined whether the various
      biological actions of different GH isoforms impact on postexercise homeostasis.

PMID- 11232002
TI  - Phenotype-genotype correlation in 56 women with nonclassical congenital adrenal
      hyperplasia due to 21-hydroxylase deficiency.
AB  - Complete analysis of the CYP21 gene was performed in 56 unrelated French women
      with symptomatic nonclassical congenital adrenal hyperplasia. The mutational
      spectrum and the phenotype-genotype correlation were examined. The overall
      predominant mutation was V281L, which was present on 51% of alleles and in 80% of
      women. Three novel mutations were found: L317M, R435C, and a 5'-end gene
      conversion. Sixty-three percent of the women were carrying a severe mutation of
      the CYP21 gene, and hence risk giving birth to children with a classical form of
      the disease. In such cases, screening for heterozygosity in the partner is
      crucial. Potential genotype/phenotype correlations were examined by classifying
      the patients into three groups according to the CYP21 allelic combinations: A
      (mild/mild), B (mild/severe), and C (severe/severe). Primary amenorrhea was more
      frequent, and mean basal and stimulated 17-hydroxyprogesterone levels were higher
      in compound heterozygotes for mild and severe mutations (group B) compared with
      women with two mild mutations (group A), but there was a considerable overlap for
      individual values. Surprisingly, in two women, a severe mutation was found on
      both alleles (group C). Therefore, the phenotype cannot be accurately predicted
      from the genotype. Variability in phenotypic expression may be conditioned by
      mechanisms other than genetic heterogeneity at the CYP21 locus.

PMID- 11232003
TI  - Meal-induced thermogenesis and obesity: is a fat meal a risk factor for fat gain
      in children?
AB  - Diet composition, in particular fat intake, has been suggested to be a risk
      factor for obesity in humans. Several mechanisms may contribute to explain the
      impact of fat intake on fat gain. One factor may be the low thermogenesis induced
      by a mixed meal rich in fat. In a group of 11 girls (10.1 +/- 0.3 yr), 6 obese
      (body mass index, 25.6 +/- 0.6 kg/m(2)), and 5 nonobese (body mass index, 19 +/-
      1.6 kg/m(2)), we tested the hypothesis that a mixed meal rich in fat can elicit
      energy saving compared with an isocaloric and isoproteic meal rich in
      carbohydrate. The postabsorptive resting energy expenditure and the thermic
      effect of a meal (TEM) after a low fat (LF; 20% fat, 68% carbohydrate, and 12%
      protein) or an isocaloric (2500 kJ or 600 Cal) and isoproteic high fat (HF; 48%
      fat, 40% carbohydrate, and 12% protein) meal were measured by indirect
      calorimetry. Each girl repeated the test with a different, randomly assigned menu
      (HF or LF) 1 week after the first test. TEM, expressed as a percentage of energy
      intake was significantly higher after a LF meal than after a HF meal (6.5 +/-
      0.7% vs. 4.3 +/- 0.4%; P < 0.01). The postprandial respiratory quotient (RQ) was
      significantly higher after a LF meal than after a HF meal (0.86 +/- 0.013 vs.
      0.83 +/- 0.014; P < 0.001). The HF low carbohydrate meal induced a significantly
      lower increase in carbohydrate oxidation than the LF meal (20.3 +/- 6.2 vs. 61.3
      +/- 7.8 mg/min; P < 0.001). On the contrary, fat oxidation was significantly
      higher after a HF meal than after a LF meal (-1.3 +/- 2.4 vs. -15.1 +/- 3.6
      mg/min; P < 0.01). However, the postprandial fat storage was 8-fold higher after
      a HF meal than after a LF meal (17.2 +/- 1.7 vs. 1.9 +/- 1.8 g; P < 0.001). These
      results suggest that a high fat meal is able to induce lower thermogenesis and a
      higher positive fat balance than an isocaloric and isoproteic low fat meal.
      Therefore, diet composition per se must be taken into account among the various
      risk factors that induce obesity in children.

PMID- 11232004
TI  - Early-onset type 2 diabetes: metabolic and genetic characterization in the
      mexican population.
AB  - The objective of this study was to investigate possible defects in the insulin
      sensitivity and/or the acute insulin response in a group of Mexican patients
      displaying early-onset type 2 diabetes and to evaluate the contribution of
      mutations in three of the genes linked to maturity-onset diabetes of the young.
      We studied 40 Mexican patients with an age of diagnosis between 20 and 40 yr in
      which the insulin sensitivity as well as the insulin secretory response were
      measured using the minimal model approach. A partial screening for possible
      mutations in 3 of the 5 genes linked to maturity-onset diabetes of the young was
      carried out by PCR-single strand conformation polymorphism analysis. A low
      insulin secretory capacity (AIRg = 68.5 +/- 5 muU/mL.min) and a near-normal
      insulin sensitivity (3.43 +/- 0.2 min/muU.mL x 10(4)) were found in these
      patients. Among this group we found two individuals carrying missense mutations
      in exon 4 of the hepatocyte nuclear factor-1alpha (HNF-4alpha) gene (Asp(126)-
      >His/Tyr and Arg(154)-->Gln, respectively) and one carrying a nonsense mutation
      in exon 7 of the HNF-1alpha gene (Gln(486)-->stop codon); 7.5% had positive
      titers for glutamic acid decarboxylase antibodies. Thirty-five percent of cases
      had insulin resistance; these subjects had the lipid abnormalities seen in the
      metabolic syndrome. A defect in insulin secretion is the hallmark in Mexican
      diabetic patients diagnosed between 20 and 40 yr of age. Mutations in either the
      HNF-1alpha or the HNF-4alpha genes are present among the individuals who develop
      early-onset diabetes in our population. These particular sequence changes have
      not been previously reported and therefore represent putative new mutations. Even
      in the absence of endogenous hyperinsulinemia, insulin resistance is associated
      with an adverse lipid profile.

PMID- 11232005
TI  - The insulin-like growth factor system in human immunodeficiency virus infection:
      relations to immunological parameters, disease progression, and antiretroviral
      therapy.
AB  - Endocrine dysfunctions have previously been reported in human immunodeficiency
      virus (HIV) infection. In this study we evaluated the relation of immunological
      parameters, virus load, clinical stage, and wasting to several parameters of the
      insulin-like growth factor (IGF) system in 76 patients with HIV infection, of
      whom 37 had developed acquired immune deficiency syndrome (AIDS). A subgroup of
      26 untreated patients was followed during longitudinal testing, while the effects
      of antiretroviral therapy were evaluated in 34 patients (nucleoside analogs in 9,
      nucleoside analogs in combination with protease inhibitors in 25). Twenty healthy
      sex- and age-matched controls were analyzed for comparison. IGF-II was decreased
      (P = 0.03) and IGF-binding protein-2 (IGFBP-2) and IGFBP-3 protease activity were
      increased (P < 0.001) in AIDS patients compared with other HIV-infected
      individuals and controls. Plasma levels of IGFBP-2 and IGFBP-3 protease activity
      correlated positively to virus load (P < 0.001) and tumor necrosis factor-alpha
      (P < 0.025) and negatively to CD4(+) and CD8(+) cell counts (P < 0.001). AIDS
      patients with wasting (n = 13) had lower IGF-II levels (P = 0.001) and higher
      IGFBP-2 levels (P = 0.001) than other AIDS patients. Although no significant
      change in any of the IGF-parameters was observed in patients during
      antiretroviral therapy, patients with elevated IGFBP-3 protease activity before
      therapy (5 of 34) all had a decrease during treatment. During longitudinal
      testing in patients followed without antiretroviral therapy, disease progression
      was associated with increases in IGFBP-3 protease activity and IGFBP-2 levels.
      Our results reveal several alterations in the IGF system during HIV infection
      with decreased IGF-II levels, increased concentration of IGFBP-2, and an
      increased IGFBP-3 protease activity in advanced disease.

PMID- 11232006
TI  - Autosomal dominant transmission of congenital thyroid hypoplasia due to loss-of
      function mutation of PAX8.
AB  - Congenital hypothyroidism (CH) is a relatively frequent and potentially severe
      disease. It is classically subdivided into: 1) thyroid dysgenesis (TD), a defect
      in the organogenesis of the gland leading to hypoplastic, ectopic, or absent
      thyroid gland; or 2) thyroid dyshormonogenesis, a defect in one of the
      biochemical mechanisms responsible for thyroid hormone synthesis. Most cases of
      TD are sporadic, although familial occurrences have occasionally been described.
      Recently, several genes have been implicated in a small proportion of TD, but, in
      the majority of the cases, the etiology remains unknown. PAX8 is a transcription
      factor involved in thyroid development. So far, three loss-of-function mutations
      of PAX8 have been described, two in sporadic cases and one in familial thyroid
      hypoplasia. Here, we describe a novel mutation of PAX8 causing autosomal dominant
      transmission of CH with thyroid hypoplasia. The mutation consists of the
      substitution of a tyrosine for cysteine 57 in the paired domain of PAX8. When
      tested in cotransfection experiments with a thyroid peroxidasse promoter
      construct, the mutant allele was unable to exert its normal transactivation
      effect on transcription. Our results give further evidence that, contrary to the
      situation in knockout mice, haplo-insufficiency of PAX8 is a cause of CH in
      humans.

PMID- 11232007
TI  - Loss of heterozygosity at the RET protooncogene locus in a case of multiple
      endocrine neoplasia type 2A.
AB  - We describe a patient affected by multiple endocrine neoplasia type 2A (MEN 2A)
      bearing a heterozygous germline mutation (Cys(634)Arg) in exon 11 and an
      additional somatic mutation of the RET protooncogene. A large intragenic
      deletion, spanning exon 4 to exon 16, affected the normal allele and was detected
      by quantitative PCR, Southern blot analysis, and screening of several polymorphic
      markers. This deletion causes RET loss of heterozygosity exclusively in the
      metastasis, thus suggesting a role for this second mutational event in tumor
      progression. No additional mutations were found in the other exons analyzed. We
      provide the first evidence that RET, a dominant oncogene, is affected by a
      germline mutation and by an additional somatic deletion of the wild-type allele.
      This unusual genetic profile may be related to the clinical course and very poor
      outcome.

PMID- 11232008
TI  - Altered control of cortisol secretion in adult men with low birth weight and
      cardiovascular risk factors.
AB  - It has been suggested that increased activity of the hypothalamic-pituitary
      adrenal axis may link low birth weight with subsequent development of
      cardiovascular risk factors and disease. Two hundred and five men, aged 66-77 yr,
      who were born and still live in East Hertfordshire underwent an overnight very
      low dose (0.25 mg) dexamethasone suppression test followed by a low dose 1
      microgram ACTH-(1-24) stimulation test. A 24-h urine sample was collected for
      analysis of cortisol metabolites by gas chromatography/electron impact mass
      spectrometry. Men with lower birth weight had enhanced responses of plasma
      cortisol to ACTH-(1-24) (P = 0.03), increased total urinary cortisol metabolite
      excretion (after adjustment for confounding effects of increased obesity and lean
      body mass in high birth weight men; P = 0.04), but no difference in plasma
      cortisol after dexamethasone. Features of the metabolic syndrome were
      independently associated with enhanced adrenal responsiveness to ACTH-(1-24)
      (raised blood pressure, P = 0.02; glucose intolerance, P = 0.09;
      hypertriglyceridemia, P = 0.02), with trends to increased urinary cortisol
      metabolite excretion, but not with differences in plasma cortisol after
      dexamethasone. Men with low birth weight and/or the metabolic syndrome have
      increased activity of the hypothalamic-pituitary-adrenal axis. This may be an
      important mechanism underpinning the effects of events in early life on later
      cardiovascular disease.

PMID- 11232009
TI  - The predominant cholecystokinin in human plasma and intestine is cholecystokinin
      33.
AB  - Cholecystokinin (CCK) occurs in multiple molecular forms; the major ones are CCK
      58, -33, -22, and -8. Their relative abundance in human plasma and intestine,
      however, is debated. To settle the issue, extracts of intestinal biopsies and
      plasma from 10 human subjects have been examined by chromatography, enzyme
      cleavages, and measurements using a library of sequence-specific RIAs. Plasma
      samples were drawn in the fasting state and at intervals after a meal. The
      abundance of the larger forms varied with the 8 C-terminal assays in the library,
      as 2 assays overestimated and 3 underestimated the amounts present. One assay,
      however, measured carboxyamidated and O:-sulfated CCKs with equimolar potency
      before and after tryptic cleavage. This assay showed that the predominant plasma
      form is CCK-33, both in the fasting state ( approximately 51%) and postprandially
      ( approximately 57%), whereas CCK-22 is the second most abundant ( approximately
      34% and 30%, respectively). In contrast, CCK-58 is less abundant in human
      intestines ( approximately 18%) and plasma ( approximately 11%). Its predominance
      in feline intestines, however, was confirmed. Hence, the results show a
      significant species variation and emphasize the necessity of highly specific and
      well characterized assays in molecular studies of CCK.

PMID- 11232010
TI  - The relationship between 24-hour growth hormone secretion and insulin-like growth
      factor I in patients with successfully treated acromegaly: impact of surgery or
      radiotherapy.
AB  - In patients with treated acromegaly, improved survival is associated with serum
      GH concentrations below 2 microgram/L (5 mU/L). A principal aim of therapy in
      acromegaly is to achieve a GH level less than 2 microgram/L, as such levels are
      thought to be "safe." However, such GH levels do not always equate with
      normalization of plasma insulin-like growth factor I (IGF-I), although
      epidemiological data linking survival or morbidity to IGF-I levels are at present
      lacking. The aims of this study were 1) to further define the nature of GH
      release in those acromegalic patients who achieve mean GH concentrations below 2
      microgram/L post therapy, 2) to examine the effect of different therapeutic
      interventions on the 24-h GH profile (surgery alone or radiotherapy), and 3) to
      determine the relationship between the various characteristics of the 24-h GH
      profile and IGF-I production in acromegalic subjects who have achieved GH below 2
      microgram/L. Spontaneous 24-h GH secretion was measured using both a conventional
      immunoradiometric assay (limit of detection, 0.4 microgram/L) and an
      ultrasensitive assay (limit of detection, 0.002 microgram/L). The GH data have
      been analyzed by several methods: 1) the pulse detection algorithm Cluster, 2) a
      distribution method for detection of peak [the observed concentration 95%, i.e.
      the threshold at or below which GH concentrations are assessed to be 95% of the
      time, as calculated by probability analysis (OC 95%)] and trough (OC, 5%) GH
      activity, 3) deconvolution analysis, and 4) approximate entropy analysis. GH was
      sampled every 20 min for 24 h, along with basal IGF-I and IGF-binding protein-3,
      in 21 treated acromegalic patients with a mean GH below 2 microgram/L [ACR; 9
      women and 12 men; median age (range), 49 (31-76) yr] and 16 healthy controls [C;
      6 women and 10 men; age, 50 (30-75) yr]. Mean 24-h serum GH concentrations were
      [median (range)]: ACR, 1.1 (0.04-1.5) microgram/L; C, 0.4 (0.02-3.3) microgram/L
      (P = 0.28). GH pulse frequency was: ACR, 11 (1-14)/24 h; C, 10 (8-18)/24 h (P =
      0.41). In the GH profiles the mean heights of the GH peaks were: ACR, 1.2 (0.05
      2.8) microgram/L; C, 0.8 (0.02-5.1) microgram/L (P = 0.91), and the mean GH
      valley nadirs were: ACR, 0.65 (0.03-1.1) microgram/L; C, 0.09 (0.01-1.8)
      microgram/L (P < 0.02). The OC 95% was: ACR, 1.0 (0.04-3.8) microgram/L; C, 1.0
      (0.02-10) microgram/L (P = 0.65), and the OC 5% was: ACR, 0.09 (0.01-0.6)
      microgram/L; C, 0.01 (0.001-0.4) microgram/L (P < 0.001). The median IGF-I was:
      ACR, 227 (100-853) microgram/L; C, 156 (89-342) microgram/L (P < 0.005).
      Approximate entrophy values were: ACR, 1.06 (0.35-1.45); and C, 0.57 (0.27-1.19);
      P < 0.05. In the acromegaly group a significant positive correlation was found
      between IGF-I and the calculated GH secretory burst amplitude in the radiotherapy
      subset (r = 0.85; P < 0.0005) as well as between IGF-I and both the mean GH
      valley nadir (r = 0.60; P < 0.004) and the trough (OC 5%) GH activity for the
      acromegalic patients as a whole (r = 0.55; P < 0.02). We conclude that in treated
      acromegaly (GH, <2 microgram/L), 1) IGF-I (by approximately 50%) and basal GH
      secretion (by 5-fold) remain significantly elevated compared with control values
      despite similar mean 24-h GH concentrations; 2) the calculated GH secretory pulse
      amplitude, mean GH valley nadir, and OC 5% correlate positively with IGF-I; 3)
      the greater mean GH valley nadir and OC 5% in acromegalic patients compared with
      controls may account for the raised IGF-I; and 4) radiotherapy is unlikely to
      normalize the GH secretory pattern, which underlies the persisting elevated IGF-I
      levels.

PMID- 11232011
TI  - Intrauterine programming of adult body composition.
AB  - Epidemiological studies suggest an association between weight in infancy and the
      risk of osteoporosis in later life. The extent to which this reflects
      environmental influences on skeletal growth and metabolism before birth or during
      the first year of postnatal life remains uncertain. We therefore examined the
      association between birth weight and adult body composition (bone, lean, and fat
      mass) in a cohort of 143 men and women, aged 70-75 yr, who were born in
      Sheffield, UK, and still lived there. The subjects underwent assessment of body
      composition by dual energy x-ray absorptiometry. Neonatal anthropometric
      information included birth weight, birth length, head size, and abdominal
      circumference. There were significant (P < 0.01) positive associations between
      birth weight and adult, whole body, bone, and lean mass among men and women.
      These were mirrored in significant (P < 0.03) associations between birth weight
      and bone mineral content at the lumbar spine and femoral neck. Associations
      between birth weight and whole body fat were weaker and not statistically
      significant. The associations of birth weight with whole body bone mineral and
      lean mass remained statistically significant after adjustment for age, sex, and
      adult height. They also remained significant after adjustment for cigarette
      smoking, alcohol consumption, dietary calcium intake, and physical inactivity.
      These data are in accord with previous observations that anthropometric measures
      in infancy are associated with skeletal size in adulthood. The presence of these
      relationships at birth adds to the evidence that bone and muscle growth may be
      programmed by genetic and/or environmental influences during intrauterine life.

PMID- 11232012
TI  - Three new mutations in the gene for the growth hormone (gh)-releasing hormone
      receptor in familial isolated gh deficiency type ib.
AB  - Isolated GH deficiency (IGHD) is familial in 5-30% of cases. The majority of
      patients have the type IB form, characterized by autosomal recessive
      transmission, low but measurable serum concentrations of GH, and responsiveness
      to exogenous GH therapy. Unique mutations in the gene encoding the GHRH receptor
      (GHRHR) have previously been described in 2 kindreds with IGHD IB. However, the
      prevalence of GHRHR mutations in patients with IGHD IB is unknown. We analyzed 30
      families with IGHD IB in which more than 1 member was affected. Linkage analysis
      was performed in 28 of the families, and in 3 families sibling pair analysis
      indicated linkage to the GHRHR gene locus. These 3 families as well as 2 families
      in which linkage analysis was not performed were screened for mutations in the 13
      coding exons, the intron-exon boundaries, and 327 bases of the promoter of the
      GHRHR gene. We identified novel GHRHR missense mutations in 2 of the 3 kindreds
      with informative linkage and in 1 family in which linkage had not been performed.
      In 1 family affected members were homozygous for a mutation in codon 144 that
      replaces leucine with histidine (L144H). Affected subjects in a second family
      were compound heterozygotes, carrying both the L144H mutation and a second
      mutation in codon 242 that replaces phenylalanine with cysteine. Affected
      subjects in a third family were homozygous for a mutation that replaces alanine
      at codon 222 with glutamic acid. All 3 mutations segregated with the IGHD
      phenotype. All 3 mutant receptors were expressed in CHO cells, and each failed to
      show a cAMP response after treatment of the cells with GHRH. These results
      demonstrate that missense mutations in the GHRHR gene are a cause of IGHD IB, and
      that defects in the GHRHR gene may be a more common cause of GH deficiency than
      previously suspected.

PMID- 11232014
TI  - Anabolic effect of estrogen replacement on bone in postmenopausal women with
      osteoporosis: histomorphometric evidence in a longitudinal study.
AB  - It is well recognized that estrogen (E(2)) prevents postmenopausal bone loss by
      suppressing bone resorption. Despite evidence that E(2) may also stimulate bone
      formation in animals, an anabolic effect in humans is still controversial. To
      investigate this, we studied 22 older postmenopausal females, with a mean age of
      65.4 yr and mean interval of 16.9 yr since menopause and low bone mineral
      density. Transcortical iliac bone biopsies were performed before and 6 yr after
      E(2) replacement therapy (ERT) [75 mg percutaneous E(2) replaced 6-monthly plus
      oral medroxy progesterone acetate (5 mg daily) for 10 days each calendar month].
      The mean serum E(2) level after 6 yr of treatment was 1077 (range, 180-2568)
      pmol/L. Bone mineral density improved in every patient, with a median increase of
      31.4% at the lumbar spine and 15.1% at the proximal femur. Bone histomorphometry
      showed an increase in cancellous bone volume from 10.75% to 17.31% (P < 0.001).
      The wall thickness after 6 yr of E(2) treatment was 38.30 micrometer compared
      with 31.20 micrometer before commencement of ERT (P < 0.0005), indicating net
      bone gain. This is the first report showing histological evidence for an increase
      in cancellous bone volume, together with an increase in wall thickness, in a
      longitudinal follow-up study of ERT in older postmenopausal women. Our results
      show that E(2) is capable of exerting an anabolic effect in women with
      osteoporosis, even when started well into the menopause.

PMID- 11232013
TI  - Rosiglitazone monotherapy is effective in patients with type 2 diabetes.
AB  - This study evaluated the efficacy and safety of rosiglitazone monotherapy in
      patients with type 2 diabetes. After a 4-week placebo run-in period, 493 patients
      with type 2 diabetes were randomized to receive rosiglitazone [2 or 4 mg twice
      daily (bd)] or placebo for 26 weeks. The primary end point was change in
      hemoglobin A(1c); other variables assessed included fasting plasma glucose,
      fructosamine, endogenous insulin secretion, urinary albumin excretion, serum
      lipids, and adverse events. Rosiglitazone (2 and 4 mg bd) decreased mean
      hemoglobin A(1c) relative to placebo by 1.2 and 1.5 percentage points,
      respectively, and reduced fasting plasma glucose concentrations relative to
      placebo by 3.22 and 4.22 mmol/L, respectively. Fasting plasma insulin and insulin
      precursor molecules decreased significantly. Homeostasis model assessment
      estimates indicate that rosiglitazone (2 and 4 mg bd) reduced insulin resistance
      by 16.0% and 24.6%, respectively, and improved ss-cell function over baseline by
      49.5% and 60.0%, respectively. Urinary albumin excretion decreased significantly
      in the rosiglitazone (4 mg bd) group. There was no increase in adverse events
      with rosiglitazone. In the short-term, rosiglitazone is an insulin sensitizer
      that is effective and safe as monotherapy in patients with type 2 diabetes who
      are inadequately controlled by lifestyle interventions.

PMID- 11232015
TI  - Apoprotein c-III and E-containing lipoparticles are markedly increased in HIV
      infected patients treated with protease inhibitors: association with the
      development of lipodystrophy.
AB  - Long-term therapy with protease inhibitors (PIs) can induce hypertriglyceridemia
      and development of a lipodystrophy. To better understand these metabolic
      alterations, the apoprotein and lipoparticle profile was investigated in male HIV
      patients under antiretroviral therapy: 49 received PIs, and 14 were given only
      two reverse transcriptase inhibitors. As controls, 63 male subjects were selected
      from a population study carried out in the Toulouse, France, area. Fasting
      glucose, insulin, and C-peptide were also determined. All patients under PIs
      displayed low levels of plasma glucose and increased insulin. PI administration
      was associated with moderate hypertriglyceridemia, low high-density cholesterol
      and apolipoprotein (apo) A-I levels. The most striking changes were a 2- to 3
      fold increase in apo E and apo C-III, essentially recovered as associated to apo
      B-containing lipoparticles. Levels of those lipoparticles were two to eight times
      above control values. About 50% of PI-treated patients had developed a patent
      lipodystrophy. Multivariate analysis revealed that, among the investigated
      parameters, apo C-III was the only one found strongly associated with the
      occurrence of lipodystrophy (odds ratio, 5.5; P: < 0.015). Finally, 13 PI
      receiving subjects with patent hypertriglyceridemia were given fenofibrate and
      were reevaluated 2 months later. Triglycerides, apo E, apo C-III, and the
      corresponding lipoparticles had returned to nearly normal levels. These results
      document the accumulation of potentially atherogenic lipoparticles under PIs. Apo
      C-III may play a pivotal role in the development of hypertriglyceridemia and
      lipodystrophy.

PMID- 11232017
TI  - Human pancreatic adenocarcinomas express parathyroid hormone-related protein.
AB  - PTH-related protein (PTHrP) is expressed in many common malignancies such as
      breast and prostate cancer and can regulate their growth. Little is known,
      however, about the role of PTHrP in pancreatic adenocarcinoma. To study PTHrP in
      pancreatic exocrine cancer, we studied its expression in pancreatic cancer cell
      lines and surgical specimens. Eight human pancreatic adenocarcinoma cell lines
      were evaluated: AsPC-1, BxPC-3, Capan-1, CFPAC-1, MIA PaCa-2, PANC-1, PANC-28,
      and PANC-48. Murine monoclonal antibodies to the amino-terminal (1-34), mid
      region (38-64), and carboxyl-terminal peptides (109-141) of PTHrP were used to
      identify cellular PTHrP and secreted PTHrP, including Western blotting and
      immunocytochemical staining for PTHrP from each cell line. Cellular PTHrP was
      detected in all cell line extracts by both Western blotting and immunoassay.
      CFPAC-1, derived from a pancreatic liver metastasis, had the highest
      concentration of PTHrP, and MIA PaCa-2, derived from primary pancreatic
      adenocarcinoma, had the lowest. PTHrP was localized by immunocytochemical
      staining in the cytoplasm in all but one cell line, and both nuclear and
      cytoplasmic immunostaining were observed in the MIA PaCa-2 and PANC-1 cells.
      Secretion of PTHrP into cell medium was also observed for each cell line and
      paralleled intracellular PTHrP levels. Evidence for differential processing of
      PTHrP expression was provided by studies demonstrating different patterns of
      PTHrP among the cell lines when assessed by PTHrP immunoassays directed against
      different PTHrP peptides. In specific, PTHrP secretion measured by a PTHrP-(38
      64) assay was highest for BxPC-3, whereas the highest levels of secreted PTHrP
      (109-141) occurred in CFPAC-1 and PANC-1. Growth of AsPC-1 cells was stimulated
      in a dose-dependent manner by PTHrP-(1-34). Immunostaining from archival tissue
      of patients with pancreatic adenocarcinoma revealed strong PTHrP expression in
      all 14 specimens. All patients were eucalcemic preoperatively. These results
      demonstrate that PTHrP is commonly expressed in pancreatic cancer. Our data
      suggest that PTHrP may have growth-regulating properties in pancreatic
      adenocarcinoma cells, but further studies are required.

PMID- 11232016
TI  - Intramuscular testosterone undecanoate and norethisterone enanthate in a clinical
      trial for male contraception.
AB  - Recent trials for hormonal male contraception are based on gestagens or GnRH
      antagonists combined with oral or injectable testosterone substitution. However,
      the efficacy of most trials remained disappointing. Norethisterone enanthate
      (NETE) has been used as a long-acting injectable female contraceptive and has
      shown sustained suppression of spermatogenesis in male monkeys and prolonged
      suppression of gonadotropins in men. This study was designed to prove the
      efficacy of the long-acting testosterone undecanoate ester (TU) alone or in
      combination with NETE in a phase II clinical trial. Fourteen healthy men received
      injections of 1000 mg TU in combination with injections of 200 mg NETE every 6
      weeks over a period of 24 weeks, followed by a control period of 28 weeks.
      Another 14 volunteers received TU alone. During the study semen variables,
      reproductive hormones, clinical chemistry and lipid parameters, well-being, and
      sexual function were monitored. Scrotal content and prostates were checked
      sonographically. During the entire treatment period mean testosterone serum
      concentrations remained within the normal limits. Marked suppression of
      gonadotropins in both treatment groups resulted in azoospermia in 7 of 14 and 13
      of 14 volunteers and in oligozoospermia in 7 of 14 and 1 of 14 in the groups
      given TU only or TU/NETE, respectively. However, the highest azoospermia rate in
      the TU/NETE group was achieved 8 weeks after the end of the treatment period, and
      1 volunteer with very high initial sperm counts (mean, 190 million/mL at
      baseline) remained oligozoospermic (10.2 million/mL). From week 20 to week 24
      there was a significant, fully reversible maximum weight gain of 3.7 kg, on the
      average, in the NETE group. In the NETE and TU alone groups there were
      significant 26.6% and 11.5% maximum decreases in high density lipoprotein
      cholesterol compared with baseline values during the treatment period. A
      significant elevation of low density lipoprotein and a decrease in lipoprotein(a)
      were detected in the TU/NETE group. In conclusion, combination treatment with
      NETE showed suppression of spermatogenesis comparable with results using
      testosterone esters in combination with GnRH antagonists or cyproterone acetate,
      but had more favorable injection intervals and better efficacy. Because of its
      long-lasting, profound suppression of spermatogenesis and the absence of serious
      side-effects, the combination of TU and NETE can be considered a first choice for
      further studies of hormonal male contraception.

PMID- 11232018
TI  - Evidence for a functional link between the heme oxygenase-carbon monoxide pathway
      and corticotropin-releasing hormone release from primary cultures of human
      trophoblast cells.
AB  - The gene expression and synthesis of both constitutive and inducible heme
      oxygenase (HO) isoforms have been recently described in human placental cells,
      but the functional role(s) of this biochemical pathway in placental physiology
      and pathology is still unclear. In the present study, we have investigated
      whether HO activity is involved in the control of CRH secretion from trophoblast
      cells. Fluctuations in HO activity were induced in primary cultures of human
      trophoblast cells using well-known activators and inhibitors of HO, and the
      subsequent changes in CRH secretion were monitored measuring CRH immunoreactivity
      released into the incubation medium. It was found that the increase in HO
      activity induced by hemin or cobalt chloride (CoCl(2)) was associated with
      parallel significant increases in CRH release. This effect was probably caused by
      the gaseous HO end-product, carbon monoxide (CO), because it was blocked by the
      HO inhibitor tin-mesoporphyrin-9, but it was not mimicked by stable HO end
      products, biliverdin and bilirubin. We have also investigated whether stimulation
      of CRH release induced by HO was mediated by the cyclooxygenase (COX) pathway.
      Indeed, hemin also caused significant increases in PGE2 release in this
      experimental paradigm. However, CoCl(2), which also enhances CRH release, had no
      stimulatory effect and actually inhibited PG secretion; moreover, a nonselective
      COX inhibitor, indomethacin, failed to counteract hemininduced CRH release. Taken
      collectively, these findings suggested that modulation of CRH secretion by the HO
      CO system occurs through a mechanism independent of COX activity.

PMID- 11232019
TI  - A developmental increase in the expression of messenger ribonucleic acid encoding
      a second form of gonadotropin-releasing hormone in the rhesus macaque
      hypothalamus.
AB  - GnRH-I is thought to represent the primary neuroendocrine link between the brain
      and the reproductive axis. Recently, however, a second molecular form of this
      decapeptide (GnRH-II) was found to be highly expressed in the brains of humans
      and nonhuman primates. In this study, in situ hybridization was used to examine
      the regional expression of GnRH-II messenger ribonucleic acid in the hypothalamus
      of immature (0.6 yr) and adult (10-15 yr) male and female rhesus macaques (Macaca
      mulatta). Overall, no sex-related differences were observed. In all of the
      animals (n = 3 animals/group), intense hybridization of a monkey GnRH-II
      riboprobe was evident in the paraventricular nucleus and supraoptic nucleus and
      to a lesser extent in the suprachiasmatic nucleus, but no age- or sex-related
      differences were apparent. Intense hybridization of the riboprobe also occurred
      in the mediobasal hypothalamus, and this was markedly greater in the adults than
      in the immature animals. These data show that the expression of GnRH-II messenger
      ribonucleic acid increases developmentally in a key neuroendocrine center of the
      brain. Moreover, because GnRH-II can stimulate LH release in vivo, it is
      plausible that changes in its gene expression represent an important component of
      the mechanism by which the hypothalamus controls reproductive function.

PMID- 11232020
TI  - Differential regulation of inhibin B and inhibin a by follicle-stimulating
      hormone and local growth factors in human granulosa cells from small antral
      follicles.
AB  - Serum inhibin B rises across the luteal-follicular transition, whereas inhibin A
      does not increase until the late follicular phase of the menstrual cycle. To test
      the hypothesis that inhibin B is secreted from preantral and small antral
      follicles and that FSH and local growth factors differentially regulate inhibin B
      and inhibin A from these developing follicles, human ovaries were obtained after
      oophorectomy. Basal secretion of inhibin B and inhibin A was examined in intact
      preantral follicles in culture (n = 6). Basal secretion and regulation of inhibin
      B and inhibin A secretion by gonadotropins, androstenedione, activin A, insulin,
      and IGF-I were examined in cultured granulosa cells from small antral follicles
      (n = 21). Inhibin B secretion from preantral follicle cultures was detectable at
      baseline (range, 17-96 pg/mL), whereas inhibin A was not detectable. In contrast,
      both inhibin B and inhibin A were detectable in granulosa cell cultures from
      small antral follicles. In granulosa cells from small antral follicles, FSH (30
      ng/mL) stimulated inhibin A 3-fold (10.5 +/- 2.2 to 32.5 +/- 8.3 IU/mL; P <
      0.001), but not inhibin B secretion (1730 +/- 354 to 2314 +/- 532 pg/mL; P = NS).
      Likewise, cAMP (1 mmol/L) stimulated inhibin A 4-fold (16.6 +/- 4.3 to 62.5 +/-
      21.9 IU/mL; P < 0.002), but not inhibin B secretion (2327 +/- 546 to 1877 +/- 377
      pg/mL; P = NS). hCG (30 ng/mL) did not stimulate inhibin A or inhibin B.
      Androstenedione (10(-)(7) mol/L), activin (30 ng/mL), insulin (30 ng/mL), and
      insulin-like growth factor I (IGF-I; 100 ng/mL) alone did not stimulate inhibin A
      or inhibin B secretion. Further, FSH-stimulated inhibin A secretion was not
      augmented by androstenedione, activin, insulin, or IGF-I. In contrast, the
      combination of IGF-I and FSH was the only treatment that stimulated inhibin B
      secretion (1742 +/- 380 to 2881 +/- 731 pg/mL; P < 0.03). However, FSH in
      combination with IGF-I resulted in greater stimulation of inhibin A (340%) than
      inhibin B (65%). These findings demonstrate that inhibin B is secreted from
      developing preantral and small antral follicles, but is not directly stimulated
      by FSH. However, the combination of FSH and IGF-I enhanced inhibin B secretion.
      In contrast, inhibin A is not secreted from preantral follicles, but in small
      antral follicles FSH and cAMP stimulate inhibin A secretion. Further, FSH in
      combination with IGF-I results in a greater degree of stimulation of inhibin A
      than of inhibin B. These findings suggest that FSH and IGF-I differentially
      regulate inhibin A and inhibin B secretion. However, additional growth factors or
      increasing granulosa cell number may contribute to the preferential serum inhibin
      B increase across the luteal-follicular transition in the menstrual cycle.

PMID- 11232021
TI  - Luteinzing hormone activity in menotropins optimizes folliculogenesis and
      treatment in controlled ovarian stimulation.
AB  - Although the role that LH plays in folliculogenesis is still controversial,
      recent evidence points toward facilitatory actions of LH activity in ovulation
      induction. Thus, we compared the response to either highly purified FSH (75 IU
      FSH/ampoule; group A, 25 subjects) or human menopausal gonadotropin (75 IU FSH
      and 75 IU LH/ampoule; group B, 25 subjects) in normoovulatory GnRH agonist
      suppressed women, candidates for intrauterine insemination. A fixed regimen of 2
      daily ampoules of highly purified FSH or human menopausal gonadotropin was
      administered in the initial 14 days of treatment; menotropin dose adjustments
      were allowed thereafter. Treatment was monitored with daily blood samples for the
      measurement of LH, FSH, 17beta-estradiol (E(2)), progesterone, testosterone, hCG,
      inhibin A, and inhibin B, and transvaginal pelvic ultrasound was performed at 2
      day intervals. Although preovulatory E(2) levels were similar, both the duration
      of treatment (16.1 +/- 0.8 vs. 12.6 +/- 0.5 days; P< 0.005) and the per cycle
      menotropin dose (33.6 +/- 2.4 vs. 23.6 +/- 1.1 ampoules; P < 0.005) were lower in
      group B. In the initial 14 treatment days the area under the curve of FSH,
      progesterone, testosterone, inhibin A, and inhibin B did not differ between the 2
      groups, whereas LH, hCG, and E(2) areas under the curve were higher in group B.
      The occurrence of small follicles (<10 mm) and the inhibin B/A ratio in the late
      follicular phase were significantly reduced in group B. A nonsignificant trend
      toward a higher multiple gestation rate was present in group A (60% vs. 17%). We
      conclude that ovulation induction with LH activity-containing menotropins is
      associated with 1) shorter treatment duration, 2) lower menotropin consumption,
      and 3) reduced development of small ovarian follicles. These features can be
      exploited to develop regimens that optimize treatment outcome, lower costs, and
      reduce occurrence of complications such as multiple gestation and ovarian
      hyperstimulation.

PMID- 11232022
TI  - Postmenopausal estrogen administration suppresses muscle sympathetic nerve
      activity.
AB  - The activity of the sympathetic nervous system shows gender-specific differences
      with lower sympathoneural activity to the muscle vascular bed in women compared
      with men, with this difference vanishing after menopause. The present study
      tested the hypothesis that estrogen exerts regulatory influence on the autonomic
      nervous system in postmenopausal women. Eleven healthy postmenopausal women (age,
      58.5 +/- 1.0 yr; mean +/- SEM) were studied in a randomized double-blind
      crossover protocol with transdermal administration of 100 microgram/day estradiol
      (E(2)) or placebo (P) for 2 days. Muscle sympathetic activity (MSA), blood
      pressure, and heart rate were recorded at rest and during sympathoexcitatory
      maneuvers (apnea, cold pressor test). E(2) administration significantly increased
      serum E(2) to physiological levels (E(2), 469.5 +/- 51.5; P, 34.8 +/- 2.2 pmol/L;
      P < 0.05) and significantly lowered MSA (E(2), 30.1 +/- 3.0 vs. P 37.7 +/- 3.1
      bursts/min; P < 0.05). At the same time, blood pressure and heart rate were not
      affected. MSA was significantly enhanced during apnea and the cold pressure test,
      and this physiological response to the maneuvers was not changed after estrogen
      supplementation. In conclusion, elevation of low postmenopausal estrogen levels
      to physiological premenopausal levels by transdermal E(2) administration
      supresses MSA. This effect is most likely the consequence of a direct E(2) effect
      on central nervous autonomic centers, which could explain the gender-specific
      differences in sympathetic outflow to the muscle vascular bed. The
      sympathoinhibitory estrogen effects could be important for beneficial
      cardiovascular effects of estrogen replacement therapy in postmenopausal women.

PMID- 11232023
TI  - Expression of muscarinic receptor types in the primate ovary and evidence for
      nonneuronal acetylcholine synthesis.
AB  - The presence of muscarinic receptors (MR) in the ovary of different species has
      been recognized, but the identity of these receptors as well as ovarian sources
      of their natural ligand, acetylcholine (ACh), have not been determined. Because
      luteinized human granulosa cells (GC) in culture express functional MR, we have
      determined whether the group of the related MR subtypes, M1R, M3R, and M5R, are
      present in vivo in human and rhesus monkey ovaries. To this end, ribonucleic
      acids (RNAs) of different human and monkey ovaries as well as RNAs from human GC
      and monkey oocytes were reverse transcribed and subjected to PCR amplification,
      followed by sequencing of the amplified complementary DNAs. Results obtained
      showed that M1R, M3R, and M5R messenger RNAs are present in adult human and
      monkey ovaries; oocytes express exclusively the M3R subtype, whereas GC express
      M1R and M5R. To determine the ovarian source(s) of the natural ligand of these
      ACh receptors, we attempted to localize the enzyme responsible for its synthesis
      with the help of a monoclonal antibody recognizing choline acetyltransferase for
      immunohistochemistry. In neither human nor monkey sections did we detect
      immunoreactive choline acetyltransferase-positive fibers or nerve cells, but,
      surprisingly, GC of antral follicles showed prominent staining. To determine
      whether GC can produce ACh, human cultured GC derived from preovulatory follicles
      were analyzed using a high pressure liquid chromatography technique. The results
      showed that these cells contained ACh in concentrations ranging from 4.2-11.5
      pmol/10(6) cells. Samples of a rat granulosa cell line likewise contained ACh.
      Thus, the ovary contains multiple MR, and GC of antral follicles are able to
      synthesize ACh, the ligand of MR. We propose that ACh may serve as an as yet
      unrecognized factor involved in the complex regulation of ovarian function in the
      primate, e.g. regulation of cell proliferation or progesterone production.

PMID- 11232024
TI  - The suppressive effect of dietary restriction and weight loss in the obese on the
      generation of reactive oxygen species by leukocytes, lipid peroxidation, and
      protein carbonylation.
AB  - Increased reactive oxygen species generation by the leukocytes of the obese may
      be responsible for increased oxidative injury to lipids and proteins and, hence,
      atherosclerosis. We have investigated whether reactive oxygen species generation
      by leukocytes and other indexes of oxidative damage in the body fall with short
      term dietary restriction and weight loss. Nine nondiabetic obese subjects (body
      mass index, 32.5-64.4 kg/m(2)), not taking any antioxidants, were put on a 1000
      Cal diet. Fasting blood samples were taken at 0, 1, 2, 3, and 4 weeks and at 12
      weeks after the cessation of dietary restriction. Blood samples were also
      obtained at 1 and 2 h after administration of 75 g oral glucose at 0 and 4 weeks.
      Mononuclear cells (MNC) and polymorphonuclear leukocytes (PMN) were isolated, and
      reactive oxygen species generation was measured. Plasma concentrations of
      thiobarbituric acid-reactive species (TBARS), 13-hydroxyoctadecadienoic acid (13
      HODE), 9-hydroxyoctadecadienoic acid (9-HODE), carbonylated proteins, o-tyrosine,
      and m-tyrosine as indexes of oxidative damage to lipids, proteins and amino
      acids, respectively, were measured. Antioxidant vitamins were measured as indexes
      of antioxidant reserves. Plasma tumor necrosis factor-alpha concentrations were
      also measured. Mean weight loss was 2.4 +/- 0.6 kg at week 1, 2.5 +/- 1.7 kg at
      week 2, 3.9 +/- 0.8 kg at week 3, and 4.5 +/- 2.8 kg at week 4 (P < 0.05).
      Reactive oxygen species generation by PMN fell from 236.4 +/- 95.8 to 150.9 +/-
      69.0, 125.9 +/- 24.3, 96.0 +/- 39.9, and 103.1 +/- 35.7 mV at weeks 1, 2, 3, and
      4, respectively (P < 0.001). It increased 3 months after the cessation of dietary
      restriction to 270.0 +/- 274.3 mV. Reactive oxygen species generation by MNC fell
      from 187.8 +/- 75.0 to 101.7 +/- 64.5, 86.9 +/- 42.8, 63.8 +/- 14.3, and 75.1 +/-
      32.2 mV and increased thereafter to 302.0 +/- 175.5 mV at 1, 2, 3, 4, and 16
      weeks, respectively (P < 0.005). Reactive oxygen species generation by PMN and
      MNC increased in response to glucose; the relative increase was greater at 4
      weeks than that at week 0 due to a fall in the basal levels of reactive oxygen
      species generation. Consistent with the fall in reactive oxygen species
      generation, there was a reduction in plasma TBARS from 1.68 +/- 0.17 micromol/L
      at week 0 to 1.47 micromol/L at 4 weeks (P < 0.05). The 13-HODE to linoleic acid
      ratio fell from a baseline of 100% to 56.4 +/- 36.1% at 4 weeks (P < 0.05), and
      the 9-HODE to linoleic acid ratio fell from a baseline of 100% to 60.5 +/- 37.7%
      at 4 weeks (P < 0.05). Carbonylated proteins fell from 1.39 +/- 0.27 microgram/mg
      protein at week 0 to 1.17 +/- 0.12 microgram/mg protein at week 4 (P < 0.05); o
      tyrosine fell from 0.42 +/- 0.03 mmol/mol phenylalanine at week 0 to 0.36 +/-
      0.02 mmol/mol phenylalanine at 4 weeks (P < 0.005), and m-tyrosine fell from 0.45
      +/- 0.04 mmol/mol phenylalanine at week 0 to 0.40 +/- 0.03 mmol/mol phenylalanine
      at 4 weeks (P < 0.05). The basal concentrations of TBARS, 9-HODE, 13-HODE,
      carbonylated proteins, o-tyrosine, and m-tyrosine in the obese were significantly
      greater than those in normal subjects. On the other hand, tumor necrosis factor
      alpha concentrations did not change during this 4-week period, nor was there any
      change in antioxidant vitamins. This is the first demonstration of 1) an increase
      in reactive oxygen species-induced damage in lipids, proteins, and amino acids in
      the obese compared with normal subjects; and 2) a decrease in reactive oxygen
      species generation by leukocytes and oxidative damage to lipids, proteins, and
      amino acids after dietary restriction and weight loss in the obese over a short
      period.

PMID- 11232025
TI  - Insulin up-regulates vascular endothelial growth factor and stabilizes its
      messengers in endometrial adenocarcinoma cells.
AB  - Angiogenesis is crucial for tumor growth and dissemination. Vascular endothelial
      growth factor (VEGF) is a potent angiogenic factor that promotes vascular growth
      and therefore tumoral growth and metastasis. Overweight, frequently associated
      with hyperinsulinemia, constitutes the major risk factor for endometrial
      carcinoma. Thus, elevated insulin levels may partly explain the increased risk of
      endometrial cancer observed in obese postmenopausal women. The aim of the present
      work was to test the role of insulin in the control of VEGF expression in
      endometrial carcinoma cells (HEC-1A). We have shown that insulin induced a
      biphasic expression of VEGF messenger ribonucleic acid, with an early, but low,
      induction (4 h of stimulation) and a delayed, but high, induction (24 h). The
      delayed effect of insulin on VEGF expression involved transcriptional and
      posttranscriptional regulation, as evidenced by the increased rate of VEGF
      transcription and the prolonged half-life of VEGF messenger ribonucleic acid.
      Simultaneously we observed higher levels of VEGF protein in the conditioned
      medium of stimulated cells compared with unstimulated ones. Therefore, insulin
      could contribute to the increased risk of endometrial carcinoma due to its
      ability to induce VEGF expression and thus participate in the maintenance of an
      angiogenic phenotype.

PMID- 11232026
TI  - Expression of melanin-concentrating hormone receptor messenger ribonucleic acid
      in tumor tissues of pheochromocytoma, ganglioneuroblastoma, and neuroblastoma.
AB  - Expression of melanin-concentrating hormone (MCH) receptor messenger ribonucleic
      acid (mRNA) was studied by RT-PCR and Northern blot analysis in human brain;
      pituitary; adrenal glands; tumor tissues of adrenal tumors,
      ganglioneuroblastomas, and neuroblastomas; and various cultured tumor cell lines.
      RT-PCR analysis showed that MCH receptor mRNA was widely expressed in brain
      tissues, pituitary, normal portions of adrenal glands (cortex and medulla), tumor
      tissues of adrenocortical tumors (12 of 13 cases), pheochromocytoma (all 7
      cases), ganglioneuroblastoma (1 case), neuroblastoma (all 5 cases), and various
      cultured tumor cell lines (6 of 7 cell lines), including 2 neuroblastoma cell
      lines. Northern blot analysis showed the expression of MCH receptor mRNA (
      approximately 2.4 kb) only in the tumor tissues of 5 pheochromocytomas, 1
      ganglioneuroblastoma, and 4 neuroblastomas, indicating that the expression levels
      of MCH receptor mRNA are much higher in these tumors than in the other tissues.
      These findings raised the possibility that MCH or MCH-like peptides may be
      related to the pathophysiology of these neural crest-derived tumors.

PMID- 11232027
TI  - Role of mitogen-activated protein kinase in prostaglandin f(2alpha) action in
      human granulosa-luteal cells.
AB  - In the ovary it has been demonstrated that PGF(2alpha) activates the
      phospholipase C (PLC)/diacylglycerol/protein kinase C pathway. However, little is
      known about the downstream signaling events that mediate subsequent cellular
      responses such as steroidogenesis. The present study was designed to examine the
      effect of PGF(2alpha) on activation of the mitogen-activated protein kinase
      (MAPK) signaling pathway and its physiological role in human granulosa-luteal
      cells (hGLCs). Human GLCs, obtained from women undergoing in vitro fertilization
      embryo transfer, were treated with increasing concentrations of PGF(2alpha) (10
      nmol/L to 10 micromol/L) for 5 min. For time-course experiments, hGLCs were
      treated with 1 micromol/L PGF(2alpha) for 1, 5, 10, or 20 min. Western blot
      analysis, using a monoclonal antibody that detected the phosphorylated forms of
      extracellular signal-regulated kinases 1 and 2 (p42(mapk) and p44(mapk),
      respectively), demonstrated that PGF(2alpha) activated MAPK in hGLCs in a dose-
      and time-dependent manner. Treatment of the cells with neomycin (10 mmol/L; a PLC
      inhibitor), bisindolylmaleimide I (5 micromol/L; a PKC inhibitor), or PD98059 (50
      micromol/L; a MEK inhibitor and a MAPK kinase inhibitor) significantly attenuated
      the PGF(2alpha)-induced activation of MAPK. In contrast, MAPK activation was not
      significantly affected by pertussis toxin (200 ng/mL; a G(i) inhibitor)
      pretreatment. To determine the role of MAPK in steroidogenesis, hGLCs were
      treated with PGF(2alpha) (1 micromol/L), hCG (1 IU/mL), or PGF(2alpha) plus hCG
      in the presence or absence of PD98059. Progesterone levels in the culture medium
      were examined by RIA. Treatment of hGLCs with PGF(2alpha) significantly inhibited
      hCG-induced progesterone production. The presence of the MEK inhibitor, PD98059,
      reversed the inhibitory effect of PGF(2alpha) on hCG-induced progesterone
      production. To our knowledge, it is the first demonstration of PGF(2alpha)
      induced activation of the MAPK signaling pathway in the human ovary. These
      results indicated that PGF(2alpha) activated MAPK subsequent to PLC and PKC
      activation through pertussis toxin-insensitive G protein in hGLCs. Further, we
      demonstrated that PGF(2alpha)-induced MAPK activation is associated with
      modulation of progesterone production. These results support the idea that the
      MAPK signaling pathway is involved in mediating PGF(2alpha) actions in the human
      ovary.

PMID- 11232028
TI  - The property of a novel v2 receptor mutant in a patient with nephrogenic diabetes
      insipidus.
AB  - Nephrogenic diabetes insipidus (NDI) is characterized by resistance of the
      kidneys to the action of arginine vasopressin (AVP); X-linked recessive NDI is
      caused by an inactivating mutation of the vasopressin type-2 (V2) receptor.
      Several missense mutations in the first or second extracellular loop of the V2
      receptor have been reported, and some of these mutant receptors were confirmed to
      have reduced affinities for ligand binding. We detected a novel V2 receptor gene
      mutation, a substitution of cysteine for arginine-104 (R104C) located in the
      first extracellular loop of the V2 receptor, in a patient with congenital NDI.
      Functional analysis by transient expression studies with COS-7 cells showed
      binding capacity of R104C mutant diminished as 10% of wild type, but binding
      affinity was strong rather than wild type. In the result of AVP stimulation
      studies, maximum cAMP accumulation of R104C decreased as 50% of wild type. On the
      other hand, a designed mutant receptor, substituted serine for arginine-104 as a
      model of modified R104C mutant receptor removed the influence of the sulfhydryl
      group in cysteine-104, recovered binding capacity up to 50% of wild type and
      maximum cAMP accumulation as 82% of wild type. Our study demonstrated that the
      R104C mutation of the V2 receptor was a cause of NDI. The mechanism of renal
      resistance to AVP was the reduction of ligand binding, and adenylyl cyclase
      activation depended on the V2 receptor. In addition, we confirmed that the
      sulfhydryl group of the cysteine-104 caused most part of R104C mutant receptor
      dysfunction.

PMID- 11232029
TI  - Pituitary chondrosarcoma: an unusual cause of a sellar mass presenting as a
      pituitary adenoma.
AB  - A 37-yr-old woman with clinical, endocrinological, and radiological features
      suggestive of a nonfunctioning pituitary tumor was found to have a chondrosarcoma
      of the pituitary sella. The bony structures around the sella were relatively
      uninvolved, other than showing minor erosion of the left side of the dorsum and
      the posterior wall of the sphenoid sinus. After partial resection of the tumor by
      the transsphenoidal route the patient received postoperative radiosurgery by a
      linear accelerator, stereotactic multiarc radiotherapy. Subsequent follow-up
      revealed reduction of the residual tumor. This case demonstrates that a
      chondrosarcoma may apparently arise directly from the pituitary fossa and
      suggests the efficacy of stereotactic radiosurgery, at least in the medium term.
      The origin, areas of involvement, management, and long-term prognosis of these
      rare tumors are reviewed.

PMID- 11232030
TI  - Ectopic lingual thyroid masquerading as thyroid cancer metastases.

PMID- 11232031
TI  - Ubiquitous expression of the calcitonin-i gene in multiple tissues in response to
      sepsis.
AB  - Calcitonin precursors (CTpr), including procalcitonin, are important markers and
      also potentially harmful mediators in response to microbial infections. The
      source and function of CTpr production in sepsis, however, remains an enigma. In
      the classical view, the transcription of the CT-I gene is restricted to
      neuroendocrine cells, in particular the C cells of the thyroid. To better
      understand the pathophysiology of CTpr induction in sepsis, we used an animal
      model analog to human sepsis, in which bacterial infection is induced in hamsters
      by implanting Escherichia coli pellets ip. Compared with control hamsters, levels
      of CTpr were elevated several fold in septic plasma and in nearly all septic
      hamster tissues analyzed. Unexpectedly, CT-messenger RNA was ubiquitously and
      uniformly expressed in multiple tissues throughout the body in response to
      sepsis. Notably, the transcriptional expression of CT-messenger RNA seemed more
      widely up-regulated in sepsis than were classical cytokines (e.g. tumor necrosis
      factor-alpha and interleukin-6). Our findings, which describe a potentially new
      mechanism of host response to a microbial infection mediated by CTpr, introduce a
      new pathophysiological role for the CT-I gene.

PMID- 11232032
TI  - Cd40 expression in uterine tissues: a key regulator of cytokine expression by
      fibroblasts.
AB  - CD40 is a cell surface receptor initially discovered on cells of the hemopoietic
      lineage. Its primary role on immune cells is to enhance their activation and
      hence their production of cytokines and immunomodulatory molecules. Recently,
      CD40 has also been detected on human fibroblasts. An emerging view of the
      fibroblast is that it is far more than a structural cell, being capable of
      intimate interaction with cells of the immune system. In fibroblasts from several
      tissues, the engagement of CD40 with its ligand (CD40L) resulted in the secretion
      of proinflammatory molecules such as interleukin-6 (IL-6) and IL-8. Currently,
      there are few data about the presence of the CD40-CD40L system in female
      reproductive tissues. This study investigates the expression of CD40 by human
      endometrium, myometrium, and cervix both in situ and in tissue explant-derived
      fibroblasts. CD40 was detected mainly in the perivascular region of endometrium,
      myometrium, and cervix. Light staining for CD40 was observed in stromal elements.
      Additionally, the basal epithelium of cervix expressed CD40. Fibroblastic cells
      derived from all three sources express low levels of CD40, and this is up
      regulated with interferon-gamma treatment (500 U/mL; 72 h). When activated with
      interferon-gamma and CD40L, the fibroblasts secreted increased amounts of IL-6,
      IL-8, and MCP-1. These data suggest that the CD40-CD40L system may provide a link
      between the resident structural cells of these reproductive tissues and the
      infiltrating immune cells or activated platelets that may express CD40L. The
      possible interaction of CD40 with CD40L may be particularly important during
      events such as menstruation and cervical ripening, where up-regulation of the
      proinflammatory molecules IL-6 and IL-8 is viewed as critical for these
      processes. In addition, dysregulation of this system may be a contributory factor
      to problems such as menstrual dysfunction and preterm labor.

PMID- 11232033
TI  - Androgen receptor expression in sertoli cells as a function of seminiferous
      tubule maturation in the human cryptorchid testis.
AB  - Androgen receptor (AR) immunohistochemistry was performed in an archival
      collection of adult human cryptorchid testes to determine whether AR cellular
      distribution and intensity of immunostaining were functions of the severity of
      cellular dysgenesis. The seminiferous tubule histology of cryptorchid testes
      collected from adults is marked by three specific patterns. 1) Seminiferous
      tubules are characterized as maintaining focal areas of germinal cell
      differentiation (albeit incomplete) that are interspersed with 2) tubules
      composed of Sertoli cells only, these latter cells being principally of the adult
      type, although dysgenetic and immature Sertoli cells may also be detected. 3) In
      contrast, there is a class of tubule that is characterized as being composed
      exclusively of Sertoli cells that are extremely dysgenetic in appearance. The
      majority of adult-type Sertoli cells found in the first types of tubules
      exhibited either robust or moderate AR staining intensity. Peritubular cells of
      these tubules also expressed a similar AR staining intensity. In contrast, in the
      more dysgenetic and immature type Sertoli cells found in the second type of
      tubules, the intensity of AR staining was significantly less, if not missing
      altogether. Finally, in the most dysgenetic tubules, Sertoli cell AR staining was
      never detected. To our knowledge, this is the first report in the literature that
      addresses the intensity of AR immunostaining in Sertoli cells of cryptorchid
      testes. The results presented herein are consistent with the interpretation that
      the intensity of AR staining in Sertoli cells diminishes as a function of the
      severity to which the cells are afflicted within a cryptorchid testis and that
      focal absence of AR expression in Sertoli cells correlates with a lack of local
      spermatogenesis in the tubules.

PMID- 11232034
TI  - Serotonergic neurons are targets for leptin in the monkey.
AB  - Leptin is a secretory product of adipocytes that has been shown to affect food
      intake, metabolism, and reproduction. One site of leptin's action is the central
      nervous system, where the leptin receptor (Ob-R) messenger ribonucleic acid
      (mRNA) and protein are expressed in discrete areas. In both the rat and monkey,
      Ob-R mRNA has been localized in the Raphe nuclei of the brainstem. Neurons in the
      Raphe nuclei are the primary source of serotonin in the brain. Serotonergic
      pathways influence both feeding and reproduction, and these cells are plausible
      direct targets for leptin's action. We used double label in situ hybridization
      and computerized image analysis to determine whether serotonergic neurons in the
      brainstem of the female pigtailed macaque (Macaca nemestrina) express Ob-R mRNA.
      We observed that many cells in the Raphe nuclei express serotonin transporter
      mRNA, a marker of serotonergic cells, and Ob-R mRNA. Based on quantitative
      analysis, the highest number of cells that express both serotonin transporter and
      Ob-R mRNAs were found in the caudal dorsal Raphe and median Raphe nuclei; fewer
      double labeled cells were situated in the caudal linear nucleus and rostral
      median Raphe, whereas double labeled cells occurred infrequently in the rostral
      dorsal Raphe. These observations suggest that leptin may act on serotonergic
      cells to mediate some of its effects on ingestive behavior, metabolism, and
      reproduction.

PMID- 11232035
TI  - Thyroid carcinoma usually occurs in patients with familial adenomatous polyposis
      in the absence of biallelic inactivation of the adenomatous polyposis coli gene.
AB  - Papillary thyroid carcinoma (PTC) is a rare extracolonic manifestation of
      familial adenomatous polyposis, determined by germline mutations of the
      adenomatous polyposis coli (APC) gene. The aim of this study was to assess the
      presence of loss of heterozygosity of APC in the thyroid tumoral tissue.
      Specimens from six female patients, aged 20-36, were analyzed for germline and
      somatic mutations of the APC gene by restriction enzyme analysis and sequence
      analysis. Five of the six also had analysis for ret/PTC, a chimeric gene, the
      activation of which is restricted to papillary TC. Because a previous study
      showed that germline mutations in familial adenomatous polyposis-associated
      thyroid carcinoma were located between codons 140 and 1513, the search for
      somatic mutations of the APC gene was restricted to this genomic area. Three of
      the six patients, belonging to the same kindred, had a germline mutation at codon
      1061. The remaining three, one per kindred, had germline mutations at codons
      1061, 1061, and 1309, respectively. None of the six patients had loss of
      heterozygosity for APC or somatic mutation in the explored genomic area (codon
      545 and codons 1061-1678). Four of five had activation of ret/PTC in the thyroid
      tumoral tissue, as ret/PTC1 isoform. Either APC has a tissue-specific dominant
      effect in the thyroid gland or the germline mutation confers a generic
      susceptibility to cancer development, but other factors (sex-related factors,
      environmental radiation, modifier genes) are also required for TC development.
      This usually involves ret/PTC activation, suggesting a possible cooperation
      between altered function of APC and gain of function of ret.

PMID- 11232036
TI  - Human melatonin regulation is not mediated by the three cone photopic visual
      system.
AB  - The aim of this study was to test if the three cone photopic visual system is the
      primary ocular photoreceptor input for human circadian regulation by determining
      the effects of different wavelengths on light-induced melatonin suppression.
      Healthy subjects with stable sleeping patterns (wake-up time 7:30 AM +/- 12 min)
      and normal color vision were exposed at night to full-field 505 nm or 555 nm
      monochromatic stimuli or darkness for 90 min. Plasma collected before and after
      exposures was quantified for melatonin. Subjects exposed to 10 irradiances at 505
      nm showed no significant differences across mean pre-exposure melatonin values
      (F=0.505). A sigmoidal fluence-response curve fitted to the melatonin suppression
      data (R(2)=0.97) indicated that 9.34 x 10(12) photons/cm(2)/sec induced a half
      saturation response (ED(50)) while 6.84 x 10(13) photons/cm(2)/sec induced a
      saturation melatonin suppression response. Further, a dose of 4.19 x 10(13)
      photon/cm(2)/sec at 505 nm was significantly stronger (P < 0.01) than an equal
      photon dose at 555 nm for melatonin suppression. These data demonstrate that the
      cone system that mediates human photopic vision is not the primary photoreceptor
      system to tranduce light stimuli for melatonin regulation.

PMID- 11232037
TI  - The effect of recombinant human tsh on the thyroid (123)i uptake in iodide
      treated normal subjects.
AB  - Radioactive iodine therapy is often successful in the treatment of toxic or non
      toxic multinodular goiter. However, when the patient has been exposed to iodine
      in the form of medication or radiocontrast agents prior to therapy, the thyroid
      radioactive iodine is often too low for successful ablation. Recently,
      administration of 0.9 mg of recombinant human TSH (rhTSH) has been shown to
      nearly double the 24-hour thyroid radioactive iodine uptake (RAIU) in euthyroid
      men living in the United States. In addition, 0.01 to 0.03 mg rhTSH administered
      24 hours prior to (131)I in patients with a history of non-toxic multinodular
      goiter residing in an area of modestly low iodine intake, has also been shown to
      increase the 24-hour thyroid radioactive iodine uptake. We now have determined
      whether rhTSH administration prior to (123)I would increase the low thyroid RAIU
      in subjects treated with sodium iodide. Nine euthyroid men were given 15 mg
      iodide daily for 7 days. There was a marked increase in serum TSH values 8 and 24
      hours after rhTSH administration, which induced elevated serum T4 and T3
      concentrations. A 16 hour thyroid RAIU was measured at baseline, after 5 days of
      iodide administration, and either 8 or 32 hours after intramuscular
      administration of rhTSH. Administration of rhTSH 8 hours before (123)I to 4
      subjects increased the 16 hour thyroid RAIU by 62% above the low post iodide
      thyroid RAIU. Administration of rhTSH 32 hours before (123)I administration to 5
      subjects increased the 16 hour thyroid RAIU by 97% above the low iodide induced
      RAIU. Thus, the overall increase in the thyroid RAIU was 88% in the 9 subjects.
      CONCLUSION: Recombinant TSH moderately increased the thyroid RAIU in subjects
      with depressed thyroid RAIU's during iodide administration and thus may be useful
      in preparing patients with non-toxic or toxic goiters and low thyroid RAIU's due
      to excess iodine for radioactive iodine treatment. Further studies to determine
      the optimal protocol to enhance the effect of rhTSH will be carried out.

PMID- 11232038
TI  - Hydrocortisone suspension and hydrocortisone tablets are not bioequivalent in the
      treatment of children with congenital adrenal hyperplasia.
AB  - In July 1998, Cortef oral suspension (Pharmacia & Upjohn) was reformulated
      changing the suspending agent tragacanth to xanthan gum. We subsequently observed
      suboptimal control of hormone levels in a group of children with classic
      congenital adrenal hyperplasia, despite increasing doses of Cortef suspension and
      stringent instructions to parents regarding shaking of the bottles of medication.
      Nineteen children receiving Cortef and fludrocortisone therapy were changed to
      hydrocortisone tablets and fludrocortisone, with a 10 percent reduction in
      hydrocortisone dose. A significant decrease in 17-hydroxyprogesterone (235 +/-
      120 vs. 27 +/- 7 nmol/L; p</=0.001) and androstenedione (18.9 +/- 18.0 vs. 3.5 +/
      3.5 nmol/L; p=0.002) was observed 4-6 weeks later. Twenty-one percent (4/19) had
      17-hydroxyprogesterone and androstenedione levels at or below the detection limit
      of the assay. Despite a significant reduction in glucocorticoid dose (19.6 +/-
      4.7 vs. 17.6 +/- 3.9 mg/M(2)/day; p<0.001), eight children experienced
      significant weight gain and appetite increase, three experienced trouble
      sleeping, four experienced moodiness, and three developed hypertension requiring
      a decrease in fludrocortisone therapy. Hydrocortisone dose was further decreased
      to 15.2 +/- 2.6 mg/M(2)/day with resolution of symptoms. We conclude that Cortef
      suspension and hydrocortisone tablets are not bioequivalent and the reformulated
      form of hydrocortisone oral suspension was inadequate in the control of children
      with congenital adrenal hyperplasia. Cortef suspension has been recalled as a
      result of these data.

PMID- 11232039
TI  - Evidence for association of polycystic ovary syndrome in caucasian women with a
      marker at the insulin receptor gene locus.
AB  - The polycystic ovary syndrome (PCOS) is one of the commonest female
      endocrinopathies affecting 5-10% of women of reproductive age. The disorder,
      characterized by chronic anovulation and signs of hyperandrogenism, results from
      a complex interaction between genetic predisposing factors and environmental
      triggers. We have studied 85 Caucasian PCOS patients and 87 age-matched Caucasian
      control women for associations with four candidate genes: follistatin, CYP19
      (aromatase), CYP17a, and the insulin receptor (INSR). These genes were analyzed
      using microsatellite markers located near or inside the genes. We found that only
      the insulin receptor gene marker D19S884 was significantly associated with PCOS
      (p=0.006 and even after a conservative correction p=0.042). The INSR gene region
      was then fine mapped with an additional panel of 9 markers but only marker
      D19S884, located 1 cM telomeric to the INSR gene, was again associated with PCOS.
      In conclusion, our results suggested that a susceptibility gene for PCOS was
      located on chromosome 19p13.3 in the insulin receptor gene region. It remains to
      be determined if this susceptibility gene is the insulin receptor gene itself or
      a closely located gene. Since insulin stimulates androgen secretion by the
      ovarian stroma it is likely that INSR function in the ovary is involved in the
      genetic susceptibility ot PCOS.

PMID- 11232040
TI  - Insulin inhibits NFkappaB and MCP-1 expression in human aortic endothelial cells.
AB  - In view of our recent demonstration that insulin inhibits the expression of
      intercellular adhesion molecule-1 (ICAM-1) and the fact that ICAM-1 expression is
      known to be modulated by nuclear factor-kappaB (NFkappaB), we have now
      investigated whether insulin inhibits intranuclear NFkappaB binding activity. We
      have also investigated whether insulin inhibits the pro-inflammatory chemokine,
      monocyte chemoattractant protein-1 (MCP-1), which attracts leucocytes to the
      inflamed sites and is also regulated by NFkappaB. Insulin was incubated with
      cultured human aortic endothelial cells (HAEC) at 0, 100 and 1000 microU/mL.
      Intranuclear NFkappaB binding activity was suppressed by approximately 45% at 100
      microU/mL and by 60% at 1000 microU/mL (p < 0.05). MCP-1 mRNA expression was also
      suppressed by 47% at 100 microU/mL and by 79% at 1000 microU/mL (p < 0.05). We
      conclude that insulin at physiologically relevant concentrations exerts an
      inhibitory effect on the cardinal pro-inflammatory transcription factor NFkappaB
      and the pro-inflammatory chemokine MCP-1; these effects suggest an anti
      inflammatory and potential anti-atherogenic effects of insulin.

PMID- 11232041
TI  - Decreased expression of Wnt7a mRNA is inversely associated with the expression of
      estrogen receptor-alpha in human uterine leiomyoma.
AB  - Wnt-7a gene not only guides the development of the anterior-posterior axis in the
      female reproductive tract, but also plays a critical role in uterine smooth
      muscle pattering and maintenance of adult uterine function. This gene is also
      responsive to changes in the levels of sex steroid hormone in the female
      reproductive tract. To explore the molecular mechanisms underlying the
      pathogenesis of uterine leiomyoma, the expression of Wnt7a mRNA in the leiomyoma
      has been assessed. RT-PCR was performed on uterine leiomyomas and the adjacent
      myometria. Of 30 cases of leiomyomas studied, 67% showed a decreased mRNA level
      as compared to the paired myometria. On the other hand, estrogen receptor-alpha
      (ER-alpha) mRNA is hyper-expressed in 67% of the leiomyomas as compared to their
      paired myometrium. An inverse association at mRNA expression was found between
      Wnt7a and ER-alpha. Miller et alhas shown that fetal exposure of DES results in
      de-regulation of Wnt7a during uterine morphogenesis. Referring to their results,
      we have postulated that hypersensitivity of leiomyoma cells to estrogen may
      deregulate the Wnt7a expression. Decreased expression of Wnt7a may lead to loss
      of control in patterning of the myometrium and result in development of leiomyoma

PMID- 11232042
TI  - Final adult height in short healthy children treated with growth hormone and
      gonadotropin-releasing hormone analogs.

PMID- 11232044
TI  - Leptin, growth hormone, and the onset of primate puberty.

PMID- 11232045
TI  - Growth signals and puberty.

PMID- 11232047
TI  - Nursing literature, nursing, and biotechnology.

PMID- 11232048
TI  - Evolution and current status of graduate programs in nursing genetics.

PMID- 11232049
TI  - Preparation of undergraduate nursing faculty to incorporate genetics content into
      curricula.

PMID- 11232050
TI  - Integrating genetics content in undergraduate nursing programs.

PMID- 11232051
TI  - State of the art: interdisciplinary collaboration for health professional
      education in genetics.
AB  - Nursing has a long and productive history of interdisciplinary cooperation in
      providing education to nurses as well as other professionals. Interdisciplinary
      education is effective in socializing students and practicing clinicians for
      practice incorporating new discoveries, in areas such as genetics, for continuing
      relevance in health care delivery. The National Coalition for Health Professional
      Education in Genetics (NCHPEG), established in 1996 with the cooperation of the
      American Nurses Association, the American Medical Association, and the National
      Human Genome Research Institute at the National Institutes of Health, has
      provided leadership in bringing advances in genetics to the nation's care
      providers in nearly all health-related disciplines. Nursing plays a key role in
      this model initiative aimed at new genetic discoveries to improve the health care
      of all Americans.

PMID- 11232052
TI  - State of the art: continuing education in nursing and genetics.

PMID- 11232053
TI  - Nursing Conference at Johns Hopkins on 19 September 1998--the patient's
      perspective: a panel discussion.

PMID- 11232055
TI  - State of the art: dissemination and utilization of nursing literature in
      practice.

PMID- 11232056
TI  - On genes and genomes mice and humans.

PMID- 11232054
TI  - State of the science: social, psychological, and ethical nursing research in
      genetics.

PMID- 11232057
TI  - State of the art and science of knowledge development in genetic nursing.

PMID- 11232058
TI  - Genetic research and knowledge in the discipline of nursing.
AB  - Nursing exists in a world in which an evidence-base for professional practice is
      required. The nursing knowledge base specific to genetics and health is currently
      not sufficient to support the expansion of nursing educational content and
      practice that is needed for health care of individual humans or families.
      Coordinated research, education, and clinical development is needed for nursing
      to meet its societal mandate for health care in response to the genetic
      revolution.

PMID- 11232059
TI  - The revictimization of child sexual abuse survivors: an examination of the
      adjustment of college women with child sexual abuse, adult sexual assault, and
      adult physical abuse.
AB  - Child sexual abuse (CSA) is associated with greater vulnerability to
      victimization in adulthood. Such experiences may have a cumulative effect. This
      study compared the adjustment of 633 women experiencing revictimization, multiple
      adult victimizations, single adult victimization, CSA only, or no victimization.
      Somatization, depression, anxiety, interpersonal sensitivity, hostility, and post
      traumatic stress disorder (PTSD) symptomatology were examined. Results support
      the cumulative effect of trauma but do not indicate differential effects for
      child to adult revictimization. Women with revictimization and multiple adult
      assaults reported more difficulties compared to women with only one form of adult
      abuse or no victimization. Women with CSA only reported similar symptoms as
      revictimized women and women with multiple adult assaults reported higher levels
      of distress than nonabused women and appeared somewhat more likely to experience
      anxiety and PTSD-related symptoms as compared to women with only adult abuse.
      Women with adult assault only and no abuse reported similar levels of distress.

PMID- 11232061
TI  - Childhood sexual abuse and dating experiences of undergraduate women.
AB  - Child sexual abuse is a prevalent social problem with a variety of negative
      consequences for adult survivors. Whereas most studies have focused on
      intrapersonal effects including depressive symptomatology and post-traumatic
      stress disorder, recent work has begun to call attention to interpersonal results
      as well. The current study examined the relationship between the experience of
      childhood sexual abuse and being a victim of psychological aggression, physical
      violence, or sexual coercion in a dating relationship in the past year.
      Participants were 219 female college undergraduates. Child sexual abuse was
      significantly related to having experienced both physical and psychological
      dating aggression even after controlling for the presence of conflict in the
      family of origin. Child sexual abuse was not significantly related to sexual
      coercion or reports of silencing oneself in relationships.

PMID- 11232060
TI  - From child victim to adult victim: a model for predicting sexual revictimization.
AB  - Women with histories of child sexual abuse (N = 221) participated in a study
      designed to test a model for predicting adult/adolescent sexual revictimization
      and post-assault functioning. Participants completed anonymous questionnaires
      regarding their sexual victimization history, post-sexual assault symptoms and
      attributions, and consensual sexual behavior. Repeated victimization was defined
      as having experienced child sexual abuse and a separate incident of
      adolescent/adult victimization. Repeated victimization was associated with having
      experienced child sexual abuse involving physical contact, including intercourse
      and/or penetration. Women with repeated victimization engaged in more self-blame,
      reported higher levels of post-traumatic symptoms, and reported more high-risk
      sexual behavior. A path model was developed that indicated that the relationship
      between revictimization and child sexual abuse was mediated by self-blame, post
      traumatic symptoms, and consensual sexual activity. The results suggest the need
      for further research on revictimization as well as suggesting areas for
      intervention to prevent sexual revictimization.

PMID- 11232062
TI  - Adult sexual revictimization among black women sexually abused in childhood: a
      prospective examination of serious consequences of abuse.
AB  - This study is a prospective investigation of adult sexual revictimization among
      113 Black women with documented histories of childhood sexual abuse. The purpose
      was to obtain information on the frequency of sexual abuse in both childhood and
      adulthood and to determine which characteristics of the child sexual abuse were
      predictive of revictimization. Thirty percent of the participants were
      revictimized and physical force predicted subsequent victimization. This study
      also investigated possible sexual behavioral correlates of revictimization.
      Revictimized women reported more involvement in prostitution and partner
      violence. Finally, the present study considered the reproductive and sexual
      health correlates of revictimization. When compared to women abused in childhood
      only, revictimized women experienced more problems conceiving, repeated vaginal
      infections, sexually transmitted diseases, and painful intercourse. Suggestions
      for intervention are discussed.

PMID- 11232063
TI  - An ecological approach to understanding sexual revictimization: linking personal,
      interpersonal, and sociocultural factors and processes.
AB  - This article applies an ecological model to the problem of sexual revictimization
      to advance the understanding of how personal, interpersonal, and sociocultural
      factors contribute to child sexual abuse victims' increased risk of being
      sexually victimized later in life. This ecological model explores how sexual
      revictimization is multiply determined by factors related to the victim's
      personal history (e.g., traumatic sexualization), the relationship in which
      revictimization occurs (e.g., decreased ability to resist unwanted sexual
      advances), the community (e.g., lack of family support), and the larger culture
      (e.g., blaming the victim attitudes). This article represents a step toward
      integrating findings on sexual revictimization and providing directions for
      future empirical work.

PMID- 11232064
TI  - Child abuse and forensic pediatric medicine fellowship curriculum statement.
AB  - Physicians have been involved in the diagnosis and treatment of victims of child
      abuse and neglect for more than 35 years. In the past decade, a cadre of
      physicians has developed extensive expertise in the field. Now, physicians are
      requested for expert consultation by medical, investigative, and legal
      colleagues. As the field advances, it has become necessary to train more
      physicians in the field of child abuse and forensic pediatrics as well as to
      standardize the curricula of the existing fellowships. A joint working group of
      the American Academy of Pediatrics Section on Child Abuse and Neglect and the
      Forensic Pediatrics Physician Leadership Group convened to develop a curriculum
      for medical fellowships in child abuse and neglect. The authors present the model
      curriculum developed by this group.

PMID- 11232065
TI  - Child abduction: an overview of current and historical perspectives.
AB  - This article summarizes research findings in the area of child abduction. Topics
      addressed include incidence rates and operational definitions of child abduction
      (legal and social), victim and offender characteristics, and motivation (e.g.,
      maternal desire, sex, retribution, profit, and desire to kill). Risk factors for
      child abduction are discussed including offender reports of victim selection
      methodology. Practical application of research findings are considered including
      the development of more scientifically sound, effective child safety training
      programs and improved investigative resource management and search methodologies.

PMID- 11232066
TI  - Do physicians have adequate knowledge of child sexual abuse? The results of two
      surveys of practicing physicians, 1986 and 1996.
AB  - The objective of this study was to to determine if physician knowledge of and
      biases regarding child sexual abuse (CSA) have changed since 1986. A
      questionnaire, previously used in 1986, was mailed to 370 physicians who see
      children in Columbus, Ohio. More respondents in 1996 correctly denied an
      association between specific sociologic factors and the likelihood of CSA.
      Seventy-two percent of physicians indicated that they check the genitalia of
      prepubescent females more than 50% of the time, versus 77% in 1986. Physicians
      who see more than 25 pediatric patients per week were significantly more likely
      to check the genitalia (p < .001), whereas physicians with more than 10 years
      experience were less likely to check genitalia (p < .05). Physicians surveyed in
      1996 were more knowledgeable about socioeconomic and behavioral aspects of CSA
      but continued to be deficient in identifying prepubescent female genital anatomy
      and in reporting suspected abuse. Education is necessary to correct these
      deficits.

PMID- 11232067
TI  - Skills and topics in continuing medical education for rural doctors.
AB  - BACKGROUND: Organizations that fund and produce continuing medical education
      (CME) activities must have up-to-date information on the needs of their
      participants. The paper describes a method for assessing priorities for the
      provision of facilities to rural doctors in Australia for educational topics and
      skills upgrades. It uses an instrument designed to establish a measure of
      knowledge and skills that records the difference between the "current felt need"
      and "desired level of competence." METHODS: A questionnaire was sent to all
      identifiable rural doctors throughout Australia, including participants in
      various types of practice. The resulting dataset is designed for future
      dissection and comparison of subsets by gender, practice size, rurality, and
      style of practice (whether procedural). It seeks to deliver a prioritized list of
      educational topics based on subjective gap analysis with weighting on the degree
      to which the need is unmet. RESULTS: There was considerable consonance between
      the major "felt needs" and other measures of need. IMPLICATIONS: In spite of
      statistical deficiencies, which would be corrected in future work, the method
      offers a new instrument to prioritize the use of resources for CME delivery.

PMID- 11232068
TI  - Self-reported effects of computer workshops on physicians' computer use.
AB  - BACKGROUND: The need for physicians to be proficient in the use of computers is
      undeniable. As computers have become easier to use and more widespread, their use
      in medicine is expanding. Several organizations have produced continuing medical
      education programs to teach physicians about the use of computers in medicine but
      little has been reported on the effects of such programs. METHOD: We present the
      self-reported effects of a series of workshops that taught physicians about basic
      computer skills: information retrieval, the Internet, CD-ROMs, electronic mail,
      and computer-aided learning. RESULTS: A questionnaire mailed to 65 workshop
      participants yielded a response rate of 46% (n = 30). Of the 30 respondents, 27%
      (n = 8) had bought new hardware or software because of attending the workshops,
      with the most common purchase being a new computer. Fifty-seven percent (n = 17)
      had increased their use of computers, with the most common applications being use
      of the Internet for information retrieval and electronic mail.

PMID- 11232069
TI  - Small-group format for continuing medical education: a report from the field.
AB  - BACKGROUND: For continuing medical education (CME) to be effective, several key
      features must be realized. These include a learner-directed agenda of topics,
      presentation of information by trusted peers or local experts, and opportunity
      for practice and feedback. If the information comes from several sources--printed
      materials, peer discussion, patient questions, and presentation from the
      specialist community--the perception of need for and the durability of change are
      enhanced. Finally, motivation for change must be high enough for change to occur,
      yet not overwhelming. METHOD: Facilitated small-group discussion among general
      practitioner colleagues with an expert specialist around clinic-based problems
      meets many of these requirements. When followed up by relevant literature, key
      concepts and practice changes are reinforced. RESULTS: We discuss our 3-year
      experience with the small-group format, comprising more than 25 sessions as
      either learners or facilitators. We describe the maturation of our group. We
      highlight the benefits to learners, including the relevance to clinical practice
      and the opportunity to ascertain the standard of care of peers. The benefits to
      the specialist are also discussed, including opportunities to learn which
      suggestions are difficult to implement. IMPLICATIONS: Our experience demonstrates
      that this format is sustainable over the long term. The success of the small
      group format at improving CME and patient outcomes deserves further evaluation.

PMID- 11232070
TI  - Need for comprehensive women's health continuing medical education among primary
      care physicians.
AB  - BACKGROUND: The Council on Graduate Medical Education's (COGME) Fifth Report on
      Women and Medicine states that "changes in undergraduate and graduate medical
      education, in addition to continuing medical education, are needed to address
      adequately the comprehensive health needs of women." Primary care physicians
      (PCPs) who completed residency training prior to the establishment of new
      guidelines for women's health education are dependent on continuing medical
      education (CME) to update their knowledge and skills. METHODS: Primary care
      physicians attending a university-based CME program in family medicine were
      surveyed (n = 300) about their need for CME in women's health topics. Responses
      were analyzed using chi-square analysis and Pearson correlations. Topics of
      interest were compared with women's health competencies published in 1997 by the
      American Board of Internal Medicine (ABIM) and in 1997 by the American Academy of
      Family Physicians (AAFP). RESULTS: Of 30 women's health topics listed, 22 were of
      interest to 50% or more of respondents and 11 were of very high interest (p <
      .05). Respondents most interested in women's health CME were most likely to
      believe CME would reduce the number of referrals currently required to evaluate
      women's breast problems. Topics of interest also align well with ABIM and AAFP
      competencies in women's health. CME in comprehensive women's health care is
      therefore of high interest to our respondents and topics of greatest interest are
      identified. IMPLICATIONS: Areas of interest correlate well with new requirements
      by ABIM and AAFP and should be targeted by CME programs.

PMID- 11232071
TI  - An educational intervention to improve diagnosis and management of suspicious
      skin lesions.
AB  - BACKGROUND: Family physicians have an important clinical role in assessment and
      management of suspicious skin lesions. As a result of a previous needs assessment
      study, an educational intervention based on audit and feedback with opportunity
      for reflection on practice was introduced to 46 family physicians randomly
      allocated to either an intervention (23) or control group (23). As an educational
      tool, audit allows doctors to systematically review their practice and establish
      the quality of care they provide. When combined with feedback and comparison of
      clinical performance with peers or standards, it has been shown to increase
      learning and change behavior. METHODS: Data based on their own patients, on the
      correlation between clinical and histologic diagnosis, and excisions of skin
      lesions were collated and reported to the intervention group. RESULTS: Despite
      randomization of the doctors, the patient population of doctors in the
      intervention and control groups were significantly different in key
      characteristics, including the types of skin lesions treated. The intervention
      group of doctors showed improved performance in providing clinical information on
      pathology requests and in adequate surgical excision of skin lesions. Diagnostic
      performance did not improve significantly, but physicians' certainty of diagnosis
      did. IMPLICATIONS: This study design has highlighted the difficulty in balancing
      the use of evidence-based educational strategies in an equivalent setting to
      normal practice with evaluation of performance using measures that include
      characteristics of practitioners' patients that cannot be controlled.

PMID- 11232072
TI  - Continuing medical education-driven skills acquisition and impact on improved
      patient outcomes in family practice setting.
AB  - BACKGROUND: An abundance of educational theory, design, and delivery of
      continuing medical education (CME) learning interventions, including their impact
      on learners, are described in the health and social sciences literature. However,
      establishing a direct correlation between the acquisition of new skills by
      learners and patient outcomes as a result of a planned CME learning intervention
      has been difficult to demonstrate. METHODS: The learning intervention described
      here tested the impact of an injection skills-acquisition program for family
      physicians treating osteoarthritis of the knee by measuring patient outcomes
      using the pain and function subscales of the Western Ontario and McMaster (WOMAC)
      3.0 osteoarthritis index, a standardized and fully validated patient-centered
      outcome measurement. It was hypothesized that patients of family physicians who
      participated in this skills-acquisition CME program would benefit from treatment
      administered by their physician during the time between injection skills
      acquisition to 6 weeks post-injection. Inclusion of a validated health status
      measure administered pre- and post-injection in addition to more traditional
      faculty and participant program evaluations was deemed necessary to test this
      hypothesis. Rheumatology, orthopedic surgery, and family medicine specialists
      from across Canada were invited to contribute to the planning, curriculum
      elaboration, and delivery of the viscosupplement injector preceptorship (VIP)
      program. Thirty-nine orthopedic and rheumatology specialists agreed to serve as
      expert faculty and participated in training 474 Canadian family and general
      practitioners over 8 months. The learning intervention involved a review of
      pertinent literature by a local preceptor and a summary of recommendations of the
      planning committee, followed by demonstration of injector skills and then
      supervised practice with patients, who received hylan G-F 20 (Synvisc,
      Ridgefield, NJ) usually in the offices of the family physicians. The pain and
      function subscales of the WOMAC 3.0 questionnaire were self-administered to each
      patient in their physician's office, prior to receiving their joint injection and
      again at or near 6-weeks post-injection. Data were analyzed in the Department of
      Epidemiology and Biostatistics at The University of Western Ontario, London, ON.
      RESULTS: Clinically important statistically significant improvements in pain and
      physical function were noted in patients who received viscosupplementation
      treatment from family physicians who had recently acquired the necessary
      injection skills. Approximately three-quarters of the patients experienced a
      reduction in pain and an improvement in physical function of at least 20%.
      IMPLICATIONS: These results suggest a positive relationship between acquisition
      of a new skill by learners and improved patient outcomes as a result of this
      planned CME learning intervention.

PMID- 11232073
TI  - Overcoming remoteness in CME videoteleconferencing: "I want my MD TV".
AB  - Videoteleconferencing in continuing medical education (CME) is here to stay. In
      the growing health care climate, with increased mergers of institutions and
      facilities, education's reliance on this medium promises to grow. This project
      summary describes one large metropolitan institution's effort to improve the
      commitment to, use in, and effectiveness of videoteleconferencing in its
      multisite delivery of CME programs. The institution is a nationally renowned
      interdisciplinary teaching and research hospital health center, with more than
      1000 beds. The medical staff numbers more than 1100. The CME program, accredited
      by the Medical Society of the State of New York, sponsors more than 44 activities
      a year, awarding over 13,000 certified category 1 CME credits and serving a
      combined total of over 806 participating MDs and DOs. A study team comprised of
      the Medical Board Education Committee's Chair-director of CME, an adult education
      consultant-professor of adult education, and a visual literacy consultant
      undertook a year-long qualitative research project to explore issues, unearth
      dilemmas in practice, and generate recommendations for future policy and practice
      related to videoteleconferencing. The primary objective was to derive strategies
      for enhancing the educational effectiveness and community building potential of
      videoteleconferencing at the hospital-health center.

PMID- 11232074
TI  - Scintigraphy in the foot and ankle.
AB  - Nuclear medicine provides a number of sensitive, although unfortunately not
      always specific techniques, for the evaluation of foot pain and suspected
      infection. In most patients the 3 phase bone scan is the initial means of
      evaluation, with a labeled white cell scan included when osteomyelitis is
      suspected. Nuclear medicine studies must be interpreted with knowledge of the
      patient's history and symptoms and with close correlation to plain film findings.
      Attention to detail when acquiring images, possibly with the addition of SPECT or
      pinhole images in difficult patients, results in excellent anatomic localization
      in most patients.

PMID- 11232075
TI  - Tarsal coalition.
AB  - This article reviews the pathoanatomy, pathomechanics, and clinical features of
      tarsal coalition and examines techniques for proper radiographic evaluations. The
      relative merits of computed tomography and MR imaging also are presented.
      Finally, current indications and techniques for surgical correction are
      discussed.

PMID- 11232076
TI  - Imaging of osteochondral lesions of the talus.
AB  - A review of the literature reveals that all studies have been performed
      retrospectively. These studies have included limited numbers of low-grade lesions
      and no prospective, randomized, comparison studies have been performed to suggest
      the superiority of CT scanning over MR imaging. The following conclusions,
      however, can be made. Plain radiographs are useful in the initial evaluation of
      patients with acute or chronic complaints of ankle pain and swelling. These
      initial studies, however, may not identify all osteochondral lesions of the
      talus, particularly lower grade lesions. CT scanning can accurately identify and
      localize a lesion while defining its extent. It has been suggested that CT
      scanning can be used to assess whether bony healing has occurred at follow-up. MR
      imaging can also precisely identify, localize, and define an OLT with the
      advantage of assessing the integrity of the overlying cartilage. It can detect
      lower grade lesions with improved sensitivity and may aid in the differentiation
      of Stage II and Stage III lesions. Using the preceding observations, the
      following approach is recommended in the evaluation and work-up of an
      osteochondral lesion of the talus (Fig. 7). The patient who presents with ankle
      pain and swelling should have weight-bearing radiographs of the ankle obtained.
      If these films demonstrate an osteochondral lesion of the talus, staging of the
      lesion should be performed. In lesions that appear nondisplaced on plain
      radiography (low grade; stable), MR imaging is recommended so the clinician can
      evaluate the integrity of the overlying cartilage and assess the true stability
      of the lesion. In lesions that appear displaced on plain radiography (high grade;
      unstable), the CT scan is the preferred modality in order to provide accurate
      assessment of lesion size and location. It should be noted, however, that no
      study has prospectively [figure: see text] compared the efficacy of these two
      modalities in the evaluation of osteochondral lesions. If a symptomatic patient
      presents with negative plain films, then an initial period of immobilization
      using a cast or boot brace is recommended. This is followed by joint mobilization
      and range of motion exercises. If the patient remains symptomatic at the 4 to 6
      week followup period, then an MR image should be performed. This study provides
      information regarding soft-tissue impingement, proliferative synovitis, and other
      bony and soft-tissue pathology. The authors have found that despite the results
      of bone scintigraphy, an MR image is invariably obtained. Because of this the
      authors do not recommend bone scintigraphy in the evaluation and diagnosis of
      OLT.

PMID- 11232077
TI  - Imaging of the Achilles' tendon.
AB  - The Achilles' tendon is amenable to imaging because of its superficial location
      and the presence of surrounding fat. This article reviews the ultrasound, the MR
      image, and the radiographic appearance of the normal and damaged tendon. The
      potential value to patient management is discussed for each modality.

PMID- 11232078
TI  - Radiography of the ankle.
AB  - Proper radiographic examination is crucial in diagnosing ankle disorders. This
      article examines standard imaging techniques and special projections of the
      ankle. Normal and abnormal bony relationships of the ankle are described in
      detail to allow clinicians ease of diagnostic accuracy.

PMID- 11232079
TI  - Stress radiography.
AB  - Although stress radiography has proven helpful in the past with regards to our
      understanding of mechanisms of injury and subsequent treatment, difficulty
      persists in defining consistent criteria for stress radiography of the foot and
      ankle. Until these have been clearly determined or proven, their validity and
      applicability in helping the physician arrive at a treatment decision may be
      questioned. It seems that a careful history, physical examination, and critical
      interpretation of routine radiographs may be most effective. Stress radiographs
      may be indicated in the elite athlete as a gauge for the severity of injury and
      rehabilitation course or in preoperative planning for ankle reconstruction when
      subtalar instability is a consideration.

PMID- 11232080
TI  - Sonography of the foot and ankle.
AB  - Sonography of the foot and ankle is a quick, relatively inexpensive imaging
      modality that can be used to diagnose a variety of pathologic conditions.
      Sonography is particularly well suited for the assessment of tendons, soft-tissue
      masses, and suspected foreign bodies. Visualization of internal structural detail
      typically equals or exceeds that of MR imaging. Diagnostic accuracy, however,
      requires meticulous attention to technical parameters and proficiency with the
      transducer.

PMID- 11232081
TI  - Arthrography of the foot and ankle. Ankle and subtalar joint.
AB  - Arthrography is the intra-articular injection of contrast media. This article
      reviews the normal and pathologic findings of standard arthrography and MR
      imaging arthrography of the ankle and subtalar joint. Standard arthrography is
      used primarily after acute ankle sprains, whereas MR imaging arthrography is used
      for staging and detecting osteochondritis dissecans of the talus, anterolateral
      soft tissue impingement, and chronic lateral ankle instability.

PMID- 11232082
TI  - MR imaging of ankle marrow.
AB  - In this article the authors have attempted to distinguish the varying types of
      marrow disorders by the imaging characteristics. This is a challenging area but
      quite rewarding because the images can often be very specific.

PMID- 11232083
TI  - MR imaging of the foot and ankle.
AB  - MR imaging provides significant anatomic detail for the evaluation of disorders
      of the osseous and soft tissue structures of the foot and ankle. This article
      describes the normal anatomy and post-traumatic conditions of the ligaments and
      tendons of the ankle. Other disorders of the soft tissues and osseous structures
      discussed include plantar fasciitis, Morton's neuroma, ganglions, plantar
      fibromatosis, hemangiomas and other neoplasms, fractures and stress fractures,
      arthritides, and osteomyelitis.

PMID- 11232084
TI  - How sexual abuse interviews go astray: implications for prosecutors, police, and
      child protection services.
AB  - This article argues that child sexual abuse interviews can go astray in two
      different ways: (a) improper interviewing has the potential to elicit false
      allegations from children, and (b) clumsy interviewing does not typically produce
      false allegations, but may have other negative consequences, particularly for
      child victims. The article clarifies the distinction between the two kinds of bad
      interviewing and suggests that clumsy interviewing is the more common of the two.
      The potential negative consequences of both improper and clumsy interviewing are
      described, along with implications for prosecutors, police, and child protection
      services. In the authors' opinion, improper interviewing can probably be
      eliminated rather easily, but clumsy interviewing may be considerably more
      resistant to change.

PMID- 11232085
TI  - Fifteen years of dissociation in maltreated children: where do we go from here?
AB  - Controversies have centered on the prevalence of dissociative symptoms and
      disorders in children and adolescents, recommended treatment approaches, and the
      potential effects of suggestive interpersonal influences. Convergence among
      diverse practitioners describing dissociative children and adolescents with
      similar symptoms and maltreatment histories supports the occurrence of these
      symptom patterns. Although prevalence information has not been well studied,
      dissociative symptoms may be found in children from a variety of settings across
      a continuum of severity. There is not yet agreement on exact treatment protocols,
      but successful treatment outcomes have been reported. A challenge for future
      research is to develop assessment protocols that are derived from multiple
      sources of data, and to incorporate the latest developmental research findings
      into theory development that addresses psychobiological, family, and cultural
      factors. The study of dissociation in children and adolescents has the potential
      to clarify some puzzling child and adolescent presentations and to identify a
      process by which some children respond and adapt to traumatic environments.

PMID- 11232086
TI  - Reactive Attachment Disorder: what we know about the disorder and implications
      for treatment.
AB  - In recent years, there has been an increase in the number of children diagnosed
      with Reactive Attachment Disorder (RAD). There is considerable disagreement about
      what this entity actually entails and, in particular, what types of assessments
      and interventions to use with these children and families. Children with a
      history of maltreatment (i.e., physical, sexual, emotional abuse, and/or severe
      neglect) are particularly likely to receive this diagnosis, because the behavior
      problems often seen in these children are presumed to stem from the maladaptive
      relationships they have had with abusive caregivers. However, many children are
      receiving this diagnosis because of behavior problems that clearly extend beyond
      the DSM-IV criteria for RAD. Perhaps the most concerning consequence of the RAD
      diagnosis is the emergence of novel treatments that lack a sound theoretical
      basis or empirical support, and may potentially be traumatizing and dangerous to
      the child. Thus, the purpose of this article is to review and synthesize what is
      known about RAD and attachment disorders and to discuss implications for
      treatment.

PMID- 11232087
TI  - Cultural evidence, child maltreatment, and the law.
AB  - This article addresses child maltreatment law's use of cultural evidence. Such
      evidence, offered by immigrant and nonmainstream parents accused of child
      maltreatment, serves to mitigate intervention in families or to minimize
      punishment for the offense. The article explores how the two areas of law that
      currently regulate child maltreatment--criminal and child welfare law--approach
      the use of such evidence. Civil, child welfare law tends to formally accept and
      allow for the use of cultural evidence. Criminal law rejects cultural evidence to
      mount a formal cultural defense that would automatically exempt individuals from
      punishment for criminal acts, but the system still allows cultural evidence to
      affect legal decisions. How both systems actually use cultural evidence in
      practice, however, remains to be determined. The article offers an approach to
      encourage both legal systems to evaluate and consider cultural evidence more
      systematically and critically. The analysis also addresses likely objections to
      the proposed alternatives.

PMID- 11232088
TI  - Projective techniques and the detection of child sexual abuse.
AB  - Projective techniques (e.g., the Rorschach, Human Figure Drawings) are sometimes
      used to detect child sexual abuse. West recently conducted a meta-analysis on
      this topic, but she systematically excluded nonsignificant results. In this
      article, a reanalysis of her data is presented. The authors conclude that
      projective techniques should not be used to detect child sexual abuse. Many of
      the studies purportedly demonstrating validity are flawed, and none of the
      projective test scores have been well replicated.

PMID- 11232089
TI  - An investigation of the clinical use of the house-tree-person projective drawings
      in the psychological evaluation of child sexual abuse.
AB  - Identification and evaluation of child sexual abuse is an integral task for
      clinicians. To aid these processes, it is necessary to have reliable and valid
      psychological measures. This is an investigation of the clinical validity and use
      of the House-Tree-Person (HTP) projective drawing, a widely used diagnostic tool,
      in the assessment of child sexual abuse. HTP drawings were collected archivally
      from a sample of sexually abused children (n = 47) and a nonabused comparison
      sample (n = 82). The two samples were grossly matched for gender, ethnicity, age,
      and socioeconomic status. The protocols were scored using a quantitative scoring
      system. The data were analyzed using a discriminant function analysis. Group
      membership could not be predicted based on a total HTP score.

PMID- 11232090
TI  - The evolving law of alleged delayed memories of childhood sexual abuse.
AB  - Court cases based on recovered memories raise serious ethical and legal issues.
      This article will address the background of the recovered memory controversy from
      a legal perspective, and discuss general legal issues in repressed memory cases.
      Based on rulings in many of these cases, the article concludes with suggestions
      on steps that therapists can take to minimize their liability exposure when
      treating patients who report delayed memories of childhood sexual abuse.

PMID- 11232091
TI  - A misunderstanding regarding the duty to report suspected abuse.
AB  - Confusion exists among professionals as to the circumstances under which a
      mandatory child abuse reporter must file a report. A review of the literature
      reveals that professionals sometimes feel obligated to make reports, even though
      they harbor no suspicion that abuse actually occurred. For example, some
      individuals believe that they must report abuse allegations made by other
      individuals, even if the mandatory reporter does not suspect abuse. The authors
      found that the mandatory reporting statutes of 49 states and the District of
      Columbia do not require reports unless the reporter has a suspicion of abuse. New
      York may be an exception. The authors conclude that mandatory reporters generally
      are not required to report abuse allegations if they themselves do not suspect
      that abuse occurred. This article encourages mandatory reporters to report abuse
      as required by the law, but not make unnecessary reports out of confusion or
      misinformation.

PMID- 11232092
TI  - Prenatal drug exposure and social policy: the search for an appropriate response.
AB  - Prenatal drug exposure continues to be a controversial topic. Views of what
      constitutes an appropriate response to drug-exposed infants vary, in large part
      due to the many complex issues endemic to perinatal substance use. The purpose of
      this article is to review the controversy surrounding prenatal drug exposure,
      outline the policy dilemmas that complicate attempts to respond appropriately,
      review current practice in this area and the effectiveness of those practices,
      and offer specific recommendations as a starting point for debate. It is
      suggested that earlier controversy regarding the sequelae of prenatal drug
      exposure may be decreasing as research identifies specific and subtle deficits in
      some affected infants. It is also suggested that the postnatal effects of
      parental substance abuse (e.g., in terms of abuse/neglect, attachment, and
      development) are the more appropriate focus of child protection efforts, and that
      different disciplines must collaborate to reach a consensus regarding the nature
      of these efforts.

PMID- 11232093
TI  - The role of pastoral crisis intervention in disasters, terrorism, violence, and
      other community crises.
AB  - The term "pastoral crisis intervention" has been defined by Everly (2000) as the
      functional integration of faith-based resources with traditional crisis
      intervention assessment and intervention technologies. Pastoral crisis
      intervention has been differentiated from ministry and the provision of
      chaplaincy services. This paper provides a public health model for integrating
      pastoral crisis intervention services within the larger domain of community
      disaster response, crisis intervention, and emergency mental health.

PMID- 11232094
TI  - The assaulted staff action program (ASAP) and declines in assaults: a meta
      analysis.
AB  - Crisis intervention procedures have been demonstrated to be of assistance in
      addressing the aftermath of psychological trauma. The Assaulted Staff Action
      Program (ASAP) is a Critical Incident Stress Management (CISM) approach that has
      been associated with providing needed support to employee victims of patient
      assaults and sharp reductions in the frequency of assaults in facilities where
      ASAP has been properly fielded. The purpose of this study was to conduct a meta
      analysis of the effectiveness of ASAP in reducing frequency of assault. Results
      yielded a highly statistically significant Cohen's d of 3.1 and fail safe number
      of 202. The implications for risk management are discussed.

PMID- 11232095
TI  - Assessment of posttraumatic stress disorder four and one-half years after the
      Iraqi invasion.
AB  - In the earliest formulations of posttraumatic stress (PTS) and even posttraumatic
      stress disorder (PTSD), it was clear that war could engender PTSD within both
      primary and secondary victims. The clinical course of PTS and PTSD is not always
      clear, but the disorder may persist months and even years after the precipitating
      traumatic event. The current study was undertaken in an effort to assess the
      prevalence of PTSD in a sample of 404 Kuwaiti citizens 4.5 years after the
      invasion and occupation of Kuwait by the Iraqi Army. Results indicate a
      psychometrically assessed prevalence of PTSD of 28.4%. A subsample of 195
      students revealed a prevalence of 45.6%. If correct, these data are worrisome
      indeed and point to 1) a significant public health challenge facing the
      government of Kuwait, as well as, 2) the increased sensitivity of the young to
      traumatic stress, both personally and vicariously. Based upon the current data,
      there may exist a virtual epidemic of posttraumatic stress disorder within the
      Kuwaiti population 4.5 years after the end of the Iraqi occupation. These data
      argue the need for a comprehensive confirmatory epidemiological investigation in
      the current prevalence of posttraumatic stress disorder within the Kuwaiti
      population so that appropriate resources may be further directed to address what
      may be a significant public health problem.

PMID- 11232096
TI  - Coordination of mental health and community agencies in disaster response.
AB  - Within the past 10 years, the American Red Cross has responded to dramatic
      disasters and terrorist events that have resulted in significant loss of life and
      traumatic stress responses. These disasters have included events as diverse as
      earthquakes, explosions, and aviation accidents.

PMID- 11232097
TI  - Preventing youth violence: a CISM pre-incident approach.
AB  - Violence in the United States is a national public health epidemic, and
      increasingly, much of this violence is committed by the country's young people.
      Critical Incident Stress Management (CISM) approaches emphasize a comprehensive
      continuum of services from pre-incident training through acute care to post
      intervention services. This paper outlines a pre-incident approach to preventing
      youth violence for parents, teachers, and counselors. The approach includes the
      identification of a continuum of warning signs and five guidelines to address the
      underlying needs manifested in the warning signs. The implications are discussed.

PMID- 11232098
TI  - Crisis response to schools.
AB  - While community based crisis response teams offer needed resources to schools
      impacted by crisis, they are often not asked to help. Reports from crisis team
      leaders at the school shooting incidents at James W. Parker Middle School,
      Edinboro, Pennsylvania and Columbine High School, Littleton, Colorado are
      contrasted regarding utilization of community resources. Factors limiting the
      usefulness of community based teams include unfamiliarity with school
      organization, culture, and procedures. Key differences in school vs. community
      team precepts, decision-making, and strategic paradigms render team coordination
      difficult. Successful cross training presents opportunities for school-community
      partnership and utilization of community teams for school duty.

PMID- 11232099
TI  - Contributing factors in the aggressive crisis.
AB  - Uncontrollable acts of violence, or "aggressive crises," result from one's
      reduced ability to regulate the expression of aggressive behavior in
      interpersonal situations. Identification of factors that predict the risk for
      violence is extremely important to emergency mental health providers in the
      field. This article discusses psychiatric, constitutional, and situational
      factors associated with potentiating the aggressive crisis. Based on the
      literature reviewed it can be argued that it is important to understand
      constitutional factors that contribute to the propensity of a given client to
      behave aggressively and that these factors interact with a wide range of
      situational determinants. While the aggressive crisis should be anticipated when
      certain conditions are met, its occurrence remains difficult to predict.

PMID- 11232100
TI  - Five principles of crisis intervention: reducing the risk of premature crisis
      intervention.
AB  - Crisis intervention, as it has evolved over the last five decades, has clearly
      demonstrated its effectiveness as a tool to reduce human distress. Nevertheless,
      as with any effort to alter human behavior, there are risks associated with
      crisis intervention. One such risk is that of premature intervention. Premature
      intervention may not only waste valuable intervention resources, but may serve to
      interfere with the natural recovery mechanisms of some victims. By clearly
      defining the nature of the crisis phenomenon itself, premature intervention may
      be averted.

PMID- 11232101
TI  - Bereavement practice guidelines for health care professionals in the emergency
      department.
AB  - A panel of multidisciplinary experts in the field of emergency services was
      convened by the National Association of Social Workers in 1999 to develop
      Bereavement Practice Guidelines. Funded by the Department of Health and Human
      Services, Health Resources and Services Administration, Maternal and Child Health
      Bureau, this paper discusses the best practices in supporting the family and
      staff when a child dies suddenly in the Emergency Department. Critical stages
      ranging from preparation to follow-up are discussed that help to enhance the
      quality of care provided to the family. A final stage addresses the support needs
      of staff.

PMID- 11232102
TI  - Predicting post-incident stress in emergency personnel: a guide for mental health
      professionals on critical incident stress management teams.
AB  - The role of the Mental Health Professional (MHP) on Critical Incident Stress
      Management (CISM) teams has been described as one of assess and refer. That is,
      to assess participants who are reacting strongly to a critical incident and refer
      them for additional psychological help. The purpose of this article is to present
      guidelines, from practice and from the research literature, for MHPs to use to
      help them predict which participants are likely to experience high-stress
      reactions following the critical incident. The stages of a CISD are briefly
      described and the predictive features associated with each stage are discussed.

PMID- 11232103
TI  - Complex PTSD: a review of current issues.
AB  - The diagnostic formulation of PTSD has made a great advance since its inception
      in the early 1980s. Yet it may be argued that PTSD as now formulated does not go
      far enough in capturing the psychological response to traumatic events. The
      notion of "complex PTSD" is reviewed as an extension of the current formulations
      of PTSD. Complex PTSD transcends current formulations of PTSD in three main areas
      of disturbance: 1) complex symptom presentations, 2) characterological issues,
      and 3) vulnerability to repeated trauma. These issues are reviewed and support is
      provided for a formal recognition of "complex PTSD".

PMID- 11232104
TI  - The impact of trauma exposure on the cognitive schemas of a sample of paramedics.
AB  - This study examines disruptions in cognitive schemas (i.e., core beliefs about
      self, others, and the world) among a sample of paramedics. Two hundred fifty
      three paramedics working in non-urban and urban settings completed measures of
      non-work and work-related negative life event and trauma exposure, perceived
      social support, and cognitive schemas. Forty percent of the respondents
      experienced at least one disrupted schema and 18 percent had disrupted beliefs
      about the meaningfulness of the world. Urban paramedics experienced greater
      disruption in cognitive schemas, particularly with Other-Safety beliefs. The
      degree of disruption in schemas was independently associated with the extent of
      non-work and work-related negative life event and trauma exposure, as well as
      perceived social support. These findings suggest the importance of investigating
      disruptions of schemas as a posttraumatic sequela among emergency medical
      personnel.

PMID- 11232105
TI  - Crisis management briefings (CMB): large group crisis intervention in response to
      terrorism, disasters, and violence.
AB  - A single act of violence or terrorism can adversely affect thousands of people.
      Such acts will invariably engender a psychological morbidity that will far
      surpass any physical morbidity. Heretofore, efforts in primary and secondary
      prevention have focused largely upon the physical consequences of these
      incidents, rather than their psychological consequences. This paper describes a
      practical group psychological crisis intervention, the "crisis management
      briefing" (CMB), that may be used with large groups of individuals in the wake of
      terrorism, violence, disasters, and other crises. This intervention, which is one
      component of the Critical Incident Stress Management (CISM) crisis intervention
      system, is designed to mitigate the effects of these crises and requires anywhere
      from 45 to 75 minutes to implement. The CBM may be employed with groups ranging
      from 10 to 300 individuals at one time.

PMID- 11232106
TI  - New tools in molecular pathology.

PMID- 11232107
TI  - The development of a post-baccalaureate certificate program in molecular
      diagnostics.
AB  - A post-baccalaureate certificate program in diagnostic molecular sciences was
      created in 1995 by the Diagnostic Genetic Sciences Program in the School of
      Allied Health at the University of Connecticut. The required on-campus lecture
      and laboratory courses include basic laboratory techniques, health care issues,
      cell biology, immunology, human genetics, research, management, and molecular
      diagnostic techniques and laboratory in molecular diagnostics. These courses
      precede a 6-month, full-time practicum at an affiliated full-service molecular
      laboratory. The practicum includes amplification and blotting methods, a research
      project, and a choice of specialized electives including DNA sequencing,
      mutagenesis, in situ hybridization methods, or molecular diagnostic applications
      in microbiology. Graduates of the program are immediately eligible to sit for the
      National Credentialing Agency examination in molecular biology to obtain the
      credential Clinical Laboratory Specialist in Molecular Biology (CLSp(MB). This
      description of the University of Connecticut program may assist other laboratory
      science programs in creating similar curricula.

PMID- 11232109
TI  - Predictive value of quantitative PCR-based viral burden analysis for eight human
      herpesviruses in pediatric solid organ transplant patients.
AB  - Human herpesviruses can cause significant morbidity and mortality in pediatric
      solid organ transplant recipients. It was hypothesized that viral burden
      quantification by polymerase chain reaction using an internal calibration
      standard could aid in distinguishing between viral disease and latency. Here we
      report the results of a 2-year prospective study of 27 pediatric solid organ
      (liver, kidney, or heart) transplant recipients in which multiple samples were
      analyzed for levels of all eight human herpesviruses by internal calibration
      standard-polymerase chain reaction. Herpes simplex viruses 1 and 2, varicella
      zoster virus, and Kaposi's sarcoma-associated herpesvirus were not detected in
      any of these samples. Human herpesvirus types 6 and 7 were detected in half of
      the patients, but were present at low levels, similar to those found in reference
      populations. Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were detected in
      89% and 56% of the patients, respectively. Viral burden analysis suggested
      distinct patient populations for CMV, with a natural cutoff of 10,000 viral
      targets/ml blood strongly associated with disease. In some cases, a dramatic
      increase in CMV levels preceded clinical evidence of disease by several weeks.
      EBV viral burden was relatively high in the only patient presenting with an EBV
      syndrome. However, two other patients without evidence of EBV disease had single
      samples with high EBV burden. Rapid reduction in both EBV and CMV burden occurred
      with antiviral treatment. These data suggest that viral burden analysis using
      internal calibration standard-polymerase chain reaction for CMV, and possibly
      other herpesviruses, is an effective method for monitoring pediatric transplant
      patients for significant herpesvirus infection and response to therapy.

PMID- 11232110
TI  - Use of single nucleotide polymorphisms (SNP) and real-time polymerase chain
      reaction for bone marrow engraftment analysis.
AB  - Allogeneic bone marrow transplant engraftment assays use polymorphisms in the
      human genome to determine the relative percentages of donor and recipient cells
      present in the recipient. We describe a novel posttransplant assay approach using
      single nucleotide polymorphisms (SNPs), the most common type of polymorphism in
      humans. Using samples of defined genotype, we used real-time polymerase chain
      reaction (PCR) and allele-specific fluorescent TaqMan probes to assay a SNP of
      the cytochrome P450 CYP2C9 gene. Standard curves of chimeric mixes showed a
      linear relationship between the ratio of two alleles and the ratio of their
      respective fluorophore emission, except for mixes with a low percentage (< 5%) of
      the less common allele. We validated the SNP real-time PCR assay by comparing it
      to Southern hybridization analysis, analyzing DNA mixes in a blinded fashion with
      both methods. The correlation between the two methods was high. We have produced
      a statistical model that varies allele frequency to predict how many SNPs would
      be required to produce a functional SNP panel. Additional development will be
      necessary to produce such a panel of highly informative SNPs for clinical use. A
      real-time PCR SNP assay may ultimately provide more accurate quantification and
      shortened turnaround time compared to current post-engraftment assays.

PMID- 11232108
TI  - Molecular diagnostic approach to non-Hodgkin's lymphoma.

PMID- 11232112
TI  - PCR methods for determining B cell clonality.

PMID- 11232113
TI  - Cell phone dangers disputed.

PMID- 11232111
TI  - Severe chromosomal aberrations in pleural mesotheliomas with unusual mesodermal
      features. Comparative genomic hybridization evidence for a mesothelioma subgroup.
AB  - Malignant mesotheliomas are tumors known for their extensive heterogeneity. Apart
      from the three classical patterns, predominantly epithelioid, sarcomatoid, and
      biphasic, some rare variants do exist. In some cases, one can find uncommon
      additional mesodermal tumor components. These tumors have previously been called
      "mesodermomas" and, like regular mesotheliomas, are usually associated with a
      previous asbestos exposure. We examined eight cases of mesodermomas by light
      microscopy, immunohistochemistry and comparative genomic hybridization (CGH).
      Besides biphasic and epithelioid areas, unusual epithelial, chondroid, osseous,
      or even angioblastic elements may be found to varying degrees.
      Immunohistochemical analysis shows similar staining results as with regular
      mesotheliomas. CGH reveals a high number of chromosomal imbalances (16.5 per
      case; range, 11-27). In 10 classical biphasic mesotheliomas that served as a
      control, defects of comparable number and severity could not be detected (8 per
      case; range, 2-16). The most frequent defects of mesodermomas (losses on 1p, 4pq,
      9p, 13q, 14q, and gains on 1q and 15q), however, could also be found in
      mesotheliomas of the classical type. Thus, our results support the classification
      of the so-called mesodermomas as a separate tumor subgroup while maintaining the
      relationship to the classical mesotheliomas. Therefore, we propose to use the
      term mesodermoma for this subgroup.

PMID- 11232114
TI  - Bats occasionally get into my house. Should I be concerned about the risk of
      rabies?

PMID- 11232115
TI  - How can you tell the difference between stomach flu and food poisoning?

PMID- 11232117
TI  - Mammography goes digital.

PMID- 11232116
TI  - Water, water everywhere.

PMID- 11232118
TI  - Fever: friend or foe?

PMID- 11232120
TI  - Easing eczema.

PMID- 11232121
TI  - Coffee commotion.

PMID- 11232119
TI  - Diet drug helps keep weight off.

PMID- 11232122
TI  - Losing your mind over diabetes and hypertension?

PMID- 11232123
TI  - Needing away chemo nausea.

PMID- 11232124
TI  - Staying awake better for surgery survival.

PMID- 11232125
TI  - Protein and bone health.

PMID- 11232126
TI  - A cure for miracles.

PMID- 11232127
TI  - Getting to the stable door before the horse has bolted.

PMID- 11232128
TI  - Treating acute myocardial infarction.

PMID- 11232129
TI  - Treating acute myocardial infarction.

PMID- 11232130
TI  - Gauging the health of our health care system.

PMID- 11232131
TI  - Gauging the health of our health care system.

PMID- 11232132
TI  - Predictors of mammography use among Canadian women aged 50-69: findings from the
      1996/97 National Population Health Survey.
AB  - BACKGROUND: Screening mammography, although recommended every 2 years for women
      aged 50-69, is thought to be underused among select groups of Canadian women.
      METHODS: We used data from the 1996/97 National Population Health Survey to
      describe current patterns in mammography use (including reasons for not having a
      mammogram within the 2 years before the survey and future screening intentions)
      in Canada and to determine factors associated with nonparticipation and time
      inappropriate use (mammogram 2 or more years before the survey) among women aged
      50-69. RESULTS: Among respondents aged 50-69, 79.1% (95% confidence interval [CI]
      76.9%-81.2%) reported ever having had a mammogram, and 53.6% (95% CI 51.4%-55.9%)
      had had a recent (time-appropriate) mammogram (within the 2 years before the
      survey). Only 0.6% (95% CI 0.3%-0.9%) of recently screened women reported
      problems of access, and few reported personal or health system barriers as
      reasons for not obtaining a recent mammogram. Over 50% of the women who had not
      had a recent mammogram reported that they did not think it was necessary, and
      only 28.2% (95% CI 23.8%-32.7%) of those who had never had a mammogram planned to
      have one within the 2 years following the survey. The rate of time-appropriate
      mammography varied significantly by province, from 41.1% (95% CI 29.3%-52.9%) in
      Newfoundland to 69.4% (95% CI 61.3%-77.6%) in British Columbia. Significant
      predictors of never having had a mammogram included higher age, residence in a
      rural area, Asia as place of birth, no involvement in volunteer groups, no
      regular physician or recent medical consultations (including recent blood
      pressure check), current smoking, infrequent physical activity and no hormone
      replacement therapy. INTERPRETATION: Despite increases in mammography screening
      rates since the 1994/95 National Population Health Survey, current estimates
      indicate that almost 50% of women aged 50-69 have not had a time-appropriate
      mammogram. Our findings confirm continued low mammography participation rates
      among older women and those in rural areas, select ethnic groups and women with
      negative health care and lifestyle characteristics.

PMID- 11232133
TI  - The effect of income pooling within a call group on rates of obstetric
      intervention.
AB  - BACKGROUND: On July 1, 1997, the call group at a tertiary referral hospital in
      Ottawa changed its remuneration. The authors tested the hypothesis that change in
      an obstetric call group's remuneration from individual fee-for-service billing to
      equal sharing of the pooled group income would result in reduced rates of
      obstetric intervention. METHODS: Intervention rates were compared for the 12
      months before (1678 births) and the 12 months after (1934 births) the change.
      Data were collected on onset of labour, indication for induction of labour, mode
      of delivery and neonatal outcome. Statistical analysis was performed with
      Wilcoxon's signed-rank test. RESULTS: The mean rate of elective induction of
      labour was 38.6% in the year before the change and 33.3% in the year after the
      change (p = 0.01). There were small but statistically significant increases in
      the mean duration of labour and mean length of the second stage (p = 0.03).
      INTERPRETATION: Billing policy may affect clinical decisions. Our findings add
      weight to the literature showing increased intervention rates with fee-for
      service remuneration.

PMID- 11232134
TI  - Devolution to democratic health authorities in Saskatchewan: an interim report.
AB  - BACKGROUND: In 1995 Saskatchewan adopted a district health board structure in
      which two-thirds of members are elected and the rest are appointed. This study
      examines the opinions of board members about health care reform and devolution of
      authority from the province to the health districts. METHODS: All 357 members of
      Saskatchewan district health boards were surveyed in 1997; 275 (77%) responded.
      Analyses included comparisons between elected and appointed members and between
      members with experience as health care providers and those without such
      experience, as well as comparisons with hypotheses about how devolution would
      develop, which were advanced in a 1997 report by another group. RESULTS: Most
      respondents felt that devolution had resulted in increased local control and
      better quality of decisions. Ninety-two percent of respondents believed extensive
      reforms were necessary and 83% that changes made in the previous 5 years had been
      for the best. However, 56% agreed that there was no clear vision of the reformed
      system. A small majority (59%) perceived health care reform as having been
      designed to improve health rather than reduce spending, contrary to a previous
      hypothesis. Many respondents (76%) thought that boards were legally responsible
      for things over which they had insufficient control, and 63% perceived that they
      were too restricted by rules laid down by the provincial government, findings
      that confirm the expectation of tensions surrounding the division of authority.
      Respondents with current or former experience as health care providers were less
      likely than nonprovider respondents to believe that nonphysician health care
      providers support decisions made by the regional health boards (45% v. 63%, p =
      0.02), a result that confirmed the contention that the role of health care
      providers on the boards would be a source of tension. INTERPRETATION: Members of
      Saskatchewan district health boards supported the general goals of health care
      reform and believed that changes already undertaken had been positive. There were
      few major differences in views between appointed and elected members and between
      provider and nonprovider members. However, tensions related to authority and
      representation will require resolution.

PMID- 11232135
TI  - Proof versus plausibility: rules of engagement for the struggle to evaluate
      alternative cancer therapies.

PMID- 11232136
TI  - New insights into the physiology and pharmacology of vitamin C.

PMID- 11232137
TI  - Past concerns and future roles for regional health boards.

PMID- 11232138
TI  - Problems for clinical judgement: introducing cognitive psychology as one more
      basic science.

PMID- 11232139
TI  - Environment and health: 8. Sustainable health care and emerging ethical
      responsibilities.

PMID- 11232142
TI  - South Africa appeals to Canada to stop recruiting its MDs.

PMID- 11232141
TI  - Transfusion-transmitted malaria in Canada.
AB  - Three cases of transfusion-transmitted malaria in Canada are described. Although
      very rare, this diagnosis should be considered in transfusion recipients who have
      undiagnosed symptoms consistent with malaria. Thick and thin blood smears should
      be urgently examined to exclude this possibility.

PMID- 11232140
TI  - The fainting patient: value of the head-upright tilt-table test in adult patients
      with orthostatic intolerance.
AB  - The head-upright tilt-table (HUT) test is used primarily for the investigation of
      orthostatic symptoms. Although this test is frequently the gold standard for the
      evaluation of neurocardiogenic syncope, dysautonomia and postural orthostatic
      tachycardia syndrome, there is a debate over its diagnostic value and method. The
      authors review the physiologic basis of the HUT test, the method, patterns of
      response, indications and contraindications, and diagnostic validity. Despite its
      limitations, the HUT test is useful in patients with a variety of clinical
      manifestations induced by orthostatism. It is most useful in documenting
      objective measures of orthostatic hypertension that cannot be obtained in a
      clinical setting.

PMID- 11232143
TI  - Casinos bring ill fortune, psychiatrists warn.

PMID- 11232144
TI  - Albertans overestimate MDs' fees.

PMID- 11232145
TI  - Cardiovascular congress wrap-up.

PMID- 11232146
TI  - Winnipeg inquest recommendation could leave young MDs in lurch, expert warns.

PMID- 11232147
TI  - Multilingual medicine in the global village.

PMID- 11232148
TI  - Teen pregnancy rate down, abortion rate up.

PMID- 11232149
TI  - Manitoba increases med school enrolment in attempt to fight doctor deficit.

PMID- 11232150
TI  - ASA or low-molecular-weight heparin in the initial management of acute ischemic
      stroke complicating atrial fibrillation?

PMID- 11232151
TI  - Inhalant use and addiction in Canada.

PMID- 11232152
TI  - [B-cell content after bone marrow transplantation--molecular basis of the limited
      antibody diversity].
AB  - Despite B-cell counts and serum immunoglobulin levels usually normalized by one
      year, humoral immunity and the incidence of bacterial infections continue to be
      abnormal even after years following bone marrow transplantation. This
      immunodeficiency could be partially caused by B-cell repertoire restriction
      similar to that observed early in ontogeny. Immune reconstitution after
      haematopoietic stem cell transplantation really follows many established
      ontogenetic patterns relating to the appearance of particular membrane markers,
      immunoglobulin classes and subclasses, and onset of antigen receptor
      rearrangements. The sequence of events that occur during successful bone marrow
      transplantation can be regarded as a blueprint for immune reconstitution in other
      clinical settings as well. However, the repertoire does not resemble a fetal one,
      because it displays adult-size IgH CDR3s, adult-type immunoglobulin gene
      utilization and no evidence of bias towards any particular VH-gen family.
      Therefore, in the description and interpretation of these events, it is important
      to realize that immune reconstitution does not appear to recapitulate human fetal
      ontogeny. In terms of B lymphocyte diversity, the inadequacy of the recovering
      immune system is more likely to be explained by a combination of other factors-
      such as clonal dominance and the delayed occurrence of somatic hypermutation.

PMID- 11232153
TI  - [Antimicrobial peptides: a new way to treat bacterial infections].
AB  - The therapy of bacterial infections is currently a difficult problem of the
      contemporary medicine, mainly due to the increasing spread of resistance to
      conventional antibiotics and to the appearance of multi-resistant bacterial
      strains. Although the gene-encoded antimicrobial peptides were described for a
      while their intensive research and study of their possible clinical applications
      has started only in the recent years. These antimicrobial peptides appear to form
      part of the most ancient defense mechanisms of the phylogenesis by exerting
      cytotoxic (mainly membrane damaging) effects against many bacteria. In this
      review the author attempts to make a brief synopsis--from a medical point of view
      -of the most important antimicrobial peptides and their possible clinical
      applications.

PMID- 11232154
TI  - [Transport of newborn infants who need intensive care].
AB  - A 4-year-long experience is reported on mobile neonatal emergency transport
      service for pathological newborn babies from referral hospitals to the NICU level
      III. The area covered by the NICU consists of three counties with a total
      population of 1 million. Distance of the hospitals from the NICU ranges 0.5-115
      km, transport time varies from 0.5-5.0 hours. In the transport staff are
      dedicated neonatal team from the NICU III, the driver and the emergency medical
      technician are the employee of the National Ambulance Service. During the study
      period 385 patients were transported. Clinical condition and characteristic
      laboratory parameters of the babies at departure and arrival are analysed and
      compared to evaluate the efficacy and quality of the system. Furthermore, some
      questions regarding organisation, transit time and response time and legal
      aspects are discussed.

PMID- 11232156
TI  - [A 19th century autobiography and its author: Sandor Feichtinger (1817-1907)].

PMID- 11232155
TI  - [Precocious puberty caused by a testicular Leydig cell tumor].
AB  - Testicular tumors are very rare in boys, approximately 1.5% of these are Leydig
      cell tumors. The authors present a 4.5 year-old boy with Leydig cell tumor of
      left testis, which was associated with increased sex steroid production that
      caused precocious puberty. These tumors are benign processes in prepubertal
      children. Beyond the rarity of this case the authors would like to report about
      its diagnostic difficulties and testis-sparing remove of it. The plasma 17
      hydroxyprogesterone levels provide the distinction between congenital adrenal
      hyperplasia and Leydig cell tumor in patient with precocious puberty.

PMID- 11232157
TI  - [General and thoracic surgery in a large surgical department. The state of
      Hungarian surgery and surgeons 130 years after Balassa].

PMID- 11232158
TI  - Functional magnetic resonance imaging (fMRI) study of sex differences in a mental
      rotation task.
AB  - The main purpose of the present study was to: 1) to investigate differences
      between males and females in brain activation when performing a mental rotation
      task, 2) investigate hemisphere differences in brain activation during mental
      rotation. Brain activation was measured with functional magnetic resonance
      imaging (fMRI). Image acquisition was performed with a 1.5 Tesla Siemens Vision
      MR scanner equipped with 25 m T/m gradients. Scanning of anatomy was done with a
      T1-weighted 3D FLASH pulse sequence. Serial imaging with 70 BOLD sensitive echo
      planar (EPI) whole brain measurements was done during stimulus presentations,
      divided into 7 blocks of 10 EPI multi-slice volume measurements each. Eleven
      subjects were presented with black-and-white drawings of 3-D shapes taken from
      the set of 3-D perspective drawings developed by Shepard and Metzler [1],
      alternated with 2-D white bars as control stimuli. In the experimental condition,
      the subjects were shown 36 pairs of 3-D drawings, presented in three blocks of 12
      pairs of drawings. The drawings were always presented pairwise. On half of the
      trials, the two 3-D shapes were congruent but portrayed with different
      orientation, in the other half the two shapes were incongruent. MR data were
      analyzed with the SPM-96 analysis software. After subtraction of activity related
      to the 2-D control stimuli, clusters of significant activation were found in the
      superior parietal lobule (BA 7), more intensely over the right hemisphere, and
      bilaterally in the inferior frontal gyrus (BA 44/45). Males showed predominantly
      parietal activation, while the females showed inferior frontal activation. It is
      suggested that males and females may differ in the processing strategy used when
      approaching a 3-D mental rotation task, males using a 'gestalt' strategy and
      females using a 'serial' reasoning strategy.

PMID- 11232159
TI  - Liver transplantation. Selection, listing criteria, and preoperative management.
AB  - Although only the expansion of the donor pool will have a major impact on the
      survival of patients with decompensated cirrhosis awaiting OLT, anticipation of
      complications such as SBP may improve the likelihood of a patient surviving until
      OLT, and may ameliorate some of the major causes of morbidity of cirrhosis, such
      as osteoporosis. Close communication between the treating physicians and the
      transplant center is crucial to ensure that the patients' UNOS status can be
      appropriately adjusted if additional complications of cirrhosis, such as
      intractable ascites, have occurred.

PMID- 11232160
TI  - Current status of pediatric liver transplantation.
AB  - Increased survival for young liver transplant recipients has greatly improved.
      Increasing success has led to broader indications, thereby increasing the number
      of potential recipients. Pediatric liver centers are developing new strategies to
      cope with the ever-increasing demands for suitable size appropriate grafts. UNOS
      is in the process of updating guidelines to regulate the sharing of organs which
      become available from new surgical techniques. In the future, alternative
      therapies, such as artificial liver assist devices and techniques of cellular
      transplantation and genetic modification of hepatocytes, may decrease the number
      of children who die while waiting for a suitable organ or even obviate the need
      for the liver transplantation.

PMID- 11232161
TI  - Surgical advances in liver transplantation. Living related and split donors.
AB  - Surgical innovations to expand an exceedingly small cadaveric liver pool have
      paved the way for the more complex procedure of adult-to-adult living donation.
      Although reduced-size liver transplant (RSLT) has provided children and small
      adults with much needed small size grafts, discarding a part of the liver can no
      longer be justified in the current era of severe organ shortage. Split liver
      transplantation may eliminate the need for RSLT and may replace adult-to-adult
      pediatric donation except in urgent situations. Adult-to-adult living donation is
      a formidable undertaking that tremendously impacts adult recipients. Adult-to
      adult living donation should be approached cautiously to ensure the safety of
      living donors. Expansion of adult living donation can only be achieved when
      ethical issues of donation are resolved and long-term donor safety is
      established.

PMID- 11232162
TI  - The kidney in liver transplantation.
AB  - Early recognition and determination of the cause of renal failure in patients
      with ESLD can be difficult because of the potential interplay among various
      factors and the wide array of differential diagnoses. A systematic approach,
      however, assists clinicians to identify common and potentially reversible causes
      of ARF. It is crucial to distinguish patients with functional renal failure, such
      as HRS, from those with advanced irreversible renal disease. Isolated liver
      transplantation is the treatment of choice for the former, and CLKT may be a
      therapeutic option for the latter. Because of the ever-increasing shortage of
      donor organs, CLKT must be used judiciously. Kidney biopsy may resolve diagnostic
      dilemmas. Management of renal complications post-OLT remains a challenge for the
      physician caring for transplant patients. Modification of nephrotoxic
      immunosuppressive regimens to avoid postoperative ARF/CRI has met with variable
      results. Azathioprine has been used in place of cyclosporine. Therapy with
      polyclonal antilymphocyte preparations or anti-OKT3 monoclonal antibodies
      (Orthoclone) should be reserved for patients with delayed graft function and for
      the treatment of acute rejection. The routine use of these agents as prophylactic
      therapy is not recommended. Data on the impact of renal insufficiency on patient
      and allograft outcome are inconsistent. Nonetheless, the authors' literature
      review suggests that renal failure associated with sepsis and, except for
      patients with HRS, renal failure requiring dialysis are the most consistent
      features associated with a worse outcome. The need for preoperative or
      postoperative dialysis has no adverse effect on survival in patients with HRS. On
      long-term follow-up, despite a greater percentage of patients reaching ESRD in
      patients with HRS compared with their non-HRS counterparts, the overall outcome
      in patients with HRS following OLT is favorable. In patients with HRS requiring
      prolonged dialysis (i.e., greater than 4 weeks), however, irreversible renal
      failure may develop, necessitating CLKT. Ideally, timely referral of patients for
      OLT may avoid this complication and obviate the need for double organ
      transplantation.

PMID- 11232163
TI  - The current status of liver transplantation for primary hepatic malignancy.
AB  - Several advances have been achieved during the last years in the management of
      patients with liver cancer. The refinement of the imaging techniques and the
      better knowledge of the biology of this neoplasm have facilitated the
      establishment of useful criteria to select patients for transplantation.
      Following a strict selection policy (solitary tumors < or = 5 cm or up to 3 foci
      each one < or = 3 cm) patients with liver cancer may achieve the same survival as
      nonneoplastic subjects. Currently, the main problem is how to diminish the risk
      of tumor progression while waiting for a liver. Although at present the benefits
      of invasive treatments are ill-defined, the ongoing studies exploring new
      treatment options hopefully will succeed in preventing this complication and
      further improve the current results.

PMID- 11232164
TI  - Endoscopic management of the liver transplant patient.
AB  - The endoscopic evaluation of the asymptomatic liver transplant patient is
      essential to risk-stratify the patient for future complications related to portal
      hypertensive bleeding (i.e., presence of large varices), and to exclude findings
      (e.g., malignancy) that might preclude the patient from consideration of OLT.
      Because waiting times for transplant are longer after listing, preventive
      management becomes imperative to diminish attrition on the waiting list and
      maintain long-term success. Following OLT, endoscopy may be performed to assess a
      number of common problems: gastrointestinal blood loss that may be caused by
      anastomotic lesions; persistent portal hypertensive bleeding; biliary
      complications, including leaks and strictures; and systemic processes (e.g.,
      infectious diseases or lymphoproliferative disorder (LPD). Clearly, endoscopy
      plays an integral role in the successful management of the patient before and
      after OLT.

PMID- 11232165
TI  - Modern immunosuppression.
AB  - The current treatment of posttransplant lymphoproliferative disease (PTLD)
      includes prophylaxis at the time of transplant, decreasing or stopping
      immunosuppresion and initiation of antiviral therapy in patients with polymerase
      chain reaction or clinical evidence of PTLD, and judicial reintroduction of
      immunosuppression in patients who have cleared their PTLD and have begun to have
      rejection. The pharmacology, pharmacokinetics, notable side effects, and
      toxicities of the immunosuppressive agents are described in this article. At the
      conclusion of each section the author's current practice with these agents and
      treatment strategies are described.

PMID- 11232166
TI  - The current management of infectious diseases in the liver transplant recipient.
AB  - The spectrum of major infections after transplantation has undergone a striking
      evolution. The epidemiologic trends in infectious diseases through the last
      decade have been most notable for a dramatic decrease in the incidence of several
      opportunistic infections, largely because of advances in prophylaxis against
      these pathogens. Paralleling these trends has been an exponential rise in the
      proportion of infections caused by antimicrobial-resistant bacteria. These
      multiresistant organisms have now emerged as leading pathogens at many transplant
      centers, and their management is a daunting challenge.

PMID- 11232167
TI  - Disease recurrence following liver transplantation.
AB  - Virtually all liver diseases that necessitate orthotopic liver transplantation
      (OLT) can recur, and recurrent disease has the potential to become the most
      serious problem facing transplantation in the future. In addition, recurrence
      following transplantation provides a model to study pathogenic mechanisms of
      these diseases. While some interventions (e.g., HBIG) have been shown to alter
      the natural history of recurrent disease, most of these disease processes are not
      modified by our currently available therapies. In addition, the role of different
      immunosuppressive protocols on disease recurrence requires further definition. As
      a varying proportion of the first generation of liver transplant patients develop
      severe recurrence and graft failure, policies of organ allocation for
      retransplantation will be challenged.

PMID- 11232168
TI  - Long-term care of the liver transplant recipient.
AB  - Many liver transplant recipients are now reaching survival beyond 5 years from
      the liver transplant procedure, and many others are alive more than a decade from
      acquiring their new liver. Orthotopic liver transplant recipients enjoy the
      benefits of normal liver function, but a variety of metabolic and other medical
      problems often develop that require diagnosis and adequate management. These
      problems include hyperlipidemia, obesity, diabetes mellitus, renal disfunction,
      arterial hypertension, bone disease and neuropsychiatric syndromes. The
      gastroenterologist, internist, or local family physician is frequently called on
      to identify and treat these postoperative complications in conjunction with
      physicians at the transplant center.

PMID- 11232169
TI  - Current status of liver support systems.
AB  - The search for a support system for liver failure has been intensified. Methods
      currently being tested include those based on artificial support, on biological
      approaches (including extracorporeal liver perfusion and transplanted
      hepatocytes) as well as hybrid devices that combine artificial aspects with
      biological systems. Each of these three areas is undergoing fast technological
      and conceptual development. Controlled clinical trials are also under way.

PMID- 11232170
TI  - Xenotransplantation of the liver.
AB  - Xenotransplantation of the liver, in its broadest conception, might involve the
      transplantation of an intact organ or xenogeneic hepatocytes, or the use of an
      intact xenogeneic liver or cells as an ex vivo "device." The indications for
      xenotransplantation include not only hepatic failure but also, potentially, the
      treatment of metabolic diseases. The hurdles to xenotransplantation include
      immune, physiologic, and infectious complications. New information and progress
      in experimental systems are bringing xenotransplantation closer to clinical
      application.

PMID- 11232171
TI  - Case report of critical incident stress debriefing through translators.
AB  - The United States Navy has SPRINT (Special Psychiatric Rapid Intervention Team)
      teams stationed in National Naval Medical Center in Bethesda, Maryland, Naval
      Regional Medical Center in Portsmouth, Virginia, Naval Regional Medical Center in
      San Diego, California, and US Naval Hospital, Bremerton, Washington. These teams
      are large units of psychiatrists, psychologists, nurses, chaplains, and hospital
      corpsmen who are trained in the techniques of Critical Incident Stress using the
      model developed by Jeffrey T. Mitchell and George S. Everly, Jr. (Mitchell &
      Everly, 1996; Everly & Mitchell, 1999). In addition to these large SPRINT teams,
      smaller Critical Incident Stress Management (CISM) teams exist at several Navy
      commands, including US Naval Hospital, Jacksonville, Florida. Since the formation
      of SPRINT teams, there have been several hundred interventions done at various
      military sites. This article discusses an intervention that was particularly
      unusual in that it was done by US military personnel for the members of the
      Argentine military, none of whom could speak English.

PMID- 11232172
TI  - Coping with psychological aftermath of school violence: the teacher and the
      assaulted staff action program.
AB  - Violence in the United States has become a national public health epidemic.
      Increasingly, much of this violence has been committed by our young people.
      School settings have not been exempt from these aggressive acts, and principals,
      teachers, and support staff have been victims of murder, physical and sexual
      assaults, verbal threats, and the destruction of personal property. This present
      paper outlines a cost-effective, empirically-based, crisis intervention approach
      that was designed for health care providers, and that has immediate application
      to providers of school psychological services. Known as the Assaulted Staff
      Action Program (ASAP), ASAP has provided needed support to these employee victims
      of violence and has been associated with sharp reductions in facility violence.
      Since ASAP interventions are appropriate for all victims of violence, the
      implications of an ASAP approach for school faculty and staff victims are
      examined. The roles of school counselors in designing, fielding, and maintaining
      an ASAP program are presented.

PMID- 11232173
TI  - Disaster psychosocial services in Hong Kong--make the unseen injury seen.
AB  - While intervention services for the physical consequences of disaster and trauma
      have been in evidence for decades, only within recent years has serious attention
      been paid to the psychological consequences of disaster. This paper describes the
      development of a program of psychosocial services designed to respond to the
      needs of the people of Hong Kong in the wake of a disaster.

PMID- 11232174
TI  - Crisis intervention: a review.
AB  - Critical incidents are sudden, unexpected, often life-threatening time-limited
      events that may overwhelm an individual's capacity to respond adaptively.
      Frequently, extreme critical incident stressors may result in personal crises,
      traumatic stress, and even Posttraumatic Stress Disorder. This paper presents a
      concise, fully-referenced, state-of-the-art review of crisis intervention
      procedures within the context of Critical Incident Stress Management.

PMID- 11232175
TI  - "Pastoral crisis intervention": toward a definition.
AB  - The pastoral community represents a large and often untapped resource in times of
      crisis. It possesses a unique aggregation of characteristics that makes it
      uniquely valuable amidst the turmoil of a psychological crisis. In critical
      incidents such as terrorism, mass disasters, violence, the loss of loved ones,
      and any events wherein human actions result in injury, destruction, and/or death,
      the pastoral community may possess especially powerful restorative attributes.
      Unfortunately, heretofore, there has existed no generally recognized and accepted
      manner in which the healing factors inherent in pastoral care have been
      functionally integrated with the well-formulated principles of crisis
      intervention. This paper represents an initial effort to elucidate how the
      principles of pastoral care may be functionally integrated with those of crisis
      intervention. The amalgam shall heretofore be referred to as "pastoral crisis
      intervention" and is defined herein.

PMID- 11232176
TI  - Mental mobilization processes in critical incident stress situations.
AB  - In this article, the psychological emergency mobilization process that takes
      place in threat situations is postulated. Mental mobilization is the increased
      mental capability of the mind in critical situations to process incoming and
      stored information to enable adaptive survival responses. The processes that are
      mobilized in the service of survival are enhanced sensory awareness, focused
      attention, rapid processing of incoming data, and use of previous experience,
      enhanced memory, altered time perception, and temporary deactivation of emotional
      reactions. From a clinical standpoint, it is important that the survival value of
      these processes is understood, as survivors can be helped to feel a sense of
      accomplishment and empowerment when they are taken through a critical situation
      in a detailed way and discover that they have been able to function well and
      survive by use of their stored "experience," rapid processing of information or
      other aspects of their mental mobilization.

PMID- 11232177
TI  - Posttraumatic stress symptomatology and cancer.
AB  - The extant nosological formulations of the American Psychiatric Association
      denotes that Posttraumatic Stress Disorder (PTSD) maybe predicated upon some life
      threatening experience. Historically, combat, robbery, rape, and serious
      accidents have been included as traumatogenetic stressors. Only recently has life
      threatening illness been considered as a traumatogenetic stressor. This paper
      reviews the relativity between cancer and posttraumatic stress.

PMID- 11232178
TI  - Group crisis intervention in a school setting following an attempted suicide.
AB  - The risk of suicide is, indeed, significant during adolescence. Regardless of
      whether the suicide attempt culminates in death (suicide), serious injury, minor
      injury, or no injury at all (parasuicides), the attempt, in and of itself, will
      send shock waves through any and all groups of which the adolescent was a member.
      These friends and family members of the adolescent who attempted suicide become
      the unwilling and vicarious victims of the suicide attempt. A rapid and assertive
      emergency mental health response to any given suicide attempt is clearly
      recommended. This paper reviews the phenomenon of adolescent suicide and offers a
      case study on the use of a rapid and efficient group crisis intervention,
      referred to as a Crisis Management Briefing (CMB; Everly, 2000), directed towards
      the vicarious victims of an adolescent suicide attempt.

PMID- 11232179
TI  - Cell death at the millennium. Implications for liver diseases.
AB  - Cell death occurs by apoptosis or necrosis. Although these are morphologically
      distinct, they share similar initiating events (death receptor ligation,
      chemicals, drug hypoxia, oxidative stress), and usually involve the participation
      of mitochondria. The ultimate shape of cell death depends on the extent of
      functional collapse of mitochondria, which either leads to a rapid loss of ATP,
      swelling and lysis, or a more selective release of cytochrome c in the presence
      of sufficient ATP to activate executioner caspases, leading to the development of
      apoptosis. Apoptosis and necrosis participate in the pathogenesis of most liver
      diseases. Therapies targeting the death receptors, initiator caspases and
      mitochondria show potential promise in various liver disease, whereas targeting
      inhibition of executioner caspases may rapidly or in delayed fashion switch from
      apoptotic to necrotic cell death.

PMID- 11232180
TI  - Alcohol-induced liver disease.
AB  - Hepatic changes resulting from the regular ingestion of alcohol are many and
      include fat infiltration, alcoholic hepatitis, and cirrhosis. Only 10% to 15% of
      chronic alcoholics develop liver disease. Women are more susceptible. An area of
      considerable importance is the high prevalence of concomitant infection with
      hepatitis C virus in chronic alcoholics. Patients who have hepatitis C and
      alcohol-induced liver injury are much more likely to develop progressive liver
      disease and cirrhosis. Corticosteroid therapy has proven useful in the treatment
      of patients with severe acute alcoholic hepatitis.

PMID- 11232181
TI  - Portal hypertension, varices, and transjugular intrahepatic portosystemic shunts.
AB  - Transjugular intrahepatic protosystemic shunts (TIPS) is the newest and the least
      invasive method of eradicating varices. This article defines portal hypertension
      succinctly, describes how it gives rise to varices and their consequences, and
      briefly reviews the development, short experience with, and current status of
      TIPS.

PMID- 11232182
TI  - Ascites.
AB  - This article reviews the progress made during the last century in understanding
      and managing ascites. The list of known causes of ascites has lengthened
      considerably. There is improved understanding of the mechanism of ascites
      formation and the pathophysiology of the renal sodium retention that accompanies
      portal hypertensive ascites. Management of ascites has become substantially
      easier with the advent of new diuretics, and new procedures such as
      peritoneovenous shunting, transjugular intrahepatic portosystemic stent
      placement, and liver transplantation.

PMID- 11232183
TI  - Hepatorenal failure.
AB  - Since the description of HRS more than 100 years ago, significant advances have
      been made in understanding the pathophysiology of HRS and in the management of
      these patients. There is now a therapeutic armamentarium: medical (ornipressin
      plus plasma volume expansion), radiographic (TIPS shunt), and surgical (liver
      transplantation). The diagnosis of HRS is no longer synonymous with a death
      sentence; instead, it is a therapeutic challenge, and a coordinated approach by
      intensivists, hepatologists, nephrologists, interventional radiologists, and
      transplant surgeons is needed to continue to improve the prognosis of cirrhotic
      patients presenting with HRS. Increased understanding of HRS will allow
      preventative rather than therapeutic measures to be used. As in all fields of
      medicine, these advances will come only with innovative clinical investigation.

PMID- 11232184
TI  - Pediatric hepatology. A half-century of progress.
AB  - Treating a pediatric patient offers a unique opportunity to develop effective
      strategies to prevent progressive liver injury and to develop novel therapeutic
      regimens to reduce the need for OLT. Universal vaccination against hepatitis
      viruses will prevent cirrhosis and liver cancer. Education and counseling may
      reduce the incidence of alcoholic liver disease. Precise and early screening for
      metabolic liver disease and genetic or targeted therapy may prevent disease
      progression. A retrospective look at the 1983 National Institutes of Health
      Consensus Conference on Liver Transplantation, after more than 15 years of
      experience among many centers, indicates that liver transplantation can be
      effectively used to childhood liver disease. Projections 10 years into the future
      offer hope that liver transplantation may not be needed in the treatment of
      certain diseases such as metabolic liver disease and fulminant hepatic failure.
      Focusing on prevention or treatment of liver disease in early life, thoughtful
      medical management, precise decision making, and conscientious, creative, and
      courageous use of nontransplant options, can save both livers and lives.

PMID- 11232185
TI  - Hemochromatosis.
AB  - The recent cloning of the hemochromatosis gene (HFE) and the demonstration that a
      single missense mutation is responsible for 90% or more of patients with the
      disease, have stimulated renewed interest in all aspects of this common disease.
      The molecular tests for identifying mutations in HFE provide improved means for
      diagnosis, family screening, and population screening. Moreover, the elucidation
      of the role of the HFE gene product will provide new insights into the regulation
      of normal iron absorption and iron metabolism. In addition, it is now apparent
      that iron, even in the modest tissue concentrations, can act as a co-factor in
      potentiating cell injury in other liver diseases.

PMID- 11232186
TI  - Wilson's disease.
AB  - During the last 90 years, Wilson's hepatolenticular degeneration has evolved from
      a disease presenting insurmountable challenges to the clinician's diagnostic
      acumen to a metabolic disorder which is diagnosable woth certainty, treatable
      successfully, and even preventable.  It may be long before the genetic defect
      becomes amenable to correction and a cure of the disease becomes possible.

PMID- 11232187
TI  - Liver transplantation at the millennium. Past, present, and future.
AB  - During the past 3 decades, liver transplantation has achieved such acceptance
      that more than 12,000 qualified recipients are listed for liver transplantation
      in the United States, but unfortunately just over 4000 cadaver donor organs are
      available each year. Thus, given the increasing disparity between the number of
      potential recipients and available cadaver organs, the current challenge in liver
      transplantation is to optimize the outcome of liver transplantation from this
      limited resource. Currently under way is re-evaluation of selection criteria to
      use these 4000 cadaver liver grafts most effectively by striking the proper
      balance between medical urgency and utility. In parallel with this re-evaluation,
      there is ongoing expansion of cadaver split-liver transplantation and adult
      living related and unrelated liver transplantation. Hoped-for but as yet
      unachieved developments in liver transplantation are xenotransplantation,
      hepatocyte transplantation, and liver-directed gene therapy. Liver
      transplantation has come a long way from the initial, unsuccessful human
      transplantations in 1963, but many challenges remain.

PMID- 11232188
TI  - Fulminant hepatic failure.
AB  - In recent years, considerable progress has been made in developing specific and
      supportive medical measures that have improved prognosis in FHF. Although new
      techniques for cell culture and perfusion have also resulted in a number of
      promising devices for the provision of temporary liver support, their clinical
      efficacy is as yet uncertain. Controlled multicenter trials in well-defined
      patient groups and with standardized outcome measures will be essential to
      evaluate the clinical value of these devices properly. The same considerations
      must also apply in assessing the efficacy of hepatocyte transplantation in FHF. A
      better understanding of mechanisms responsible for liver cell death and
      multiorgan failure, and the development of strategies to enhance liver
      regeneration may, in the future, allow a more targeted approach to therapy.

PMID- 11232189
TI  - Hepatocellular cancer. A century of progress.
AB  - Although gratifying progress has been made during the 20th century, much remains
      to be achieved. The principal objective must be prevention of HCC. Prevention of
      HBV-related tumors is already feasible, and prevention of HCV-related and
      aflatoxin-induced tumors should soon become possible. Not all HCCs are yet
      accounted for causatively, and the remaining risk factors need to be identified.
      Until primary prevention can be accomplished, attention must also be directed to
      obtaining a complete understanding of the pathogenesis of HCC so that strategies
      for secondary and tertiary prevention can be formulated and instituted. Finally,
      the search for effective anticancer treatment must continue.

PMID- 11232190
TI  - Hepatic granulomas and hepatic sarcoidosis.
AB  - The causes of hepatic granulomas are numerous and their identification can be
      difficult. Sarcoidosis is a main cause of hepatic granulomas. The mechanisms that
      initiate the formation of sarcoid granulomas are unknown. This article discusses
      the pathology of hepatic sarcoidosis and hepatic granulomas.

PMID- 11232191
TI  - Viral hepatitis A, B, and C.
AB  - Mankind probably has known viral hepatitis for many centuries; however, the major
      and most dramatic developments in our knowledge of these diseases have taken
      place during the second half of the 20th century. During this relatively short
      period of time, the infectious nature of hepatitis A, B, and C has been proven,
      leading to their identification and description. The advent of serologic markers
      has provided the means for establishing the diagnosis. Epidemiologic studies have
      provided important information that led to exciting achievements in detection and
      prevention of transmission. Molecular biology studies and cell culture techniques
      have established our knowledge of the viral genomes, and led to the development
      of specific vaccines for hepatitis A and B. Anti-viral therapy has been developed
      and aggressive combination therapy has emerged as a promising strategy for
      chronic hepatitis B and C. This article reviews some of the main fields of
      progress and achievement related to viral hepatitis A, B, and C in the 20th
      century.

PMID- 11232192
TI  - Drug-induced liver disease.
AB  - Drug-induced liver disease may account for between 10% and 50% of adult patients
      with elevated enzymes, especially in patients over age 50 years. It accounts for
      nearly 25% of patients with fulminant hepatic failure. Liver injury can be
      cytotoxic, cholestatic, or mixed. A variety of systemic manifestations can
      accompany drug-induced hepatotoxicity. Drug-induced liver disease can mimic
      autoimmune hepatitis or it can evolve to cirrhosis. It can also mimic veno
      occulusive disorders. The plethora of herbal and traditional agents currently
      ingested by many people should always be considered in any patient with abnormal
      hepatic biochemistry.

PMID- 11232193
TI  - Primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune
      cholangitis.
AB  - Primary biliary cirrhosis (PBC), and autoimmune cholangitis are presumed to be
      autoimmune cholestatic diseases, but the relevant antigens are unknown. Primary
      biliary cirrhosis is diagnosed by a positive serum mitochondrial antibody test.
      It usually affects women and has a very long course, culminating in liver
      transplantation or death. Ursodeoxycholic acid is probably the appropriate
      treatment. Primary sclerosing cholangitis (PSC) is marked by progressive
      destruction of extrahepatic and intrahepatic bile ducts. There is no specific
      diagnostic test or treatment. Cholangiocarcinoma is the dreaded complication and
      precludes liver transplantation, the only chance of a cure. Autoimmune
      cholangitis overlaps PBC and autoimmune chronic hepatitis. It is a rare
      condition, resembling PBC but with a negative serum mitochondrial antibody test;
      however, serum antinuclear antibodies and smooth muscle antibodies are present in
      high titers.

PMID- 11232194
TI  - Apoptosis in hepatic pathophysiology.
AB  - Apoptosis is a fundamental biologic process that is important in many physiologic
      and pathophysiologic processes in the liver. Although dysregulation of apoptosis
      may contribute to a wide range of diseases, the role of this process in liver
      disease and pathophysiology has only recently begun to be recognized and remains
      to be fully defined. Several important questions remain unanswered: How does
      excessive apoptosis in response to injury contribute to inflammation and
      fibrogenesis in the liver? How does control of apoptosis contribute to the
      regulation of hepatic structure following injury? What is the role of death
      receptors in hepatic disease? Can an understanding of apoptosis be helpful in
      therapeutic modulation of specific liver diseases or liver cancer? The
      identification of target molecules involved in apoptosis raises the prospect of
      pharmacologic modulation that may result in better treatment options for patients
      with liver diseases. Inhibition of apoptosis is likely to be useful in treating
      fulminant hepatic failure or in organ preservation before transplantation. In
      these situations, treatment is for a limited period, and the potential hazards of
      nonselective long-term inhibition of apoptosis are minimized. Safe and organ
      specific inhibitors of apoptosis would be required for prolonged treatment of
      chronic liver diseases. For treatment of liver tumors, the goal is to induce
      apoptosis selectively in cancer cells. Drugs that decrease the apoptotic
      threshold by modulating the intracellular regulatory mechanisms and drugs that
      enhance the susceptibility of cancer cells to undergo immune-mediated apoptosis
      will be useful in the treatment of liver cancers. The rapid advances in the
      understanding of the intracellular mechanisms and the regulation of apoptosis
      will ultimately result in a better understanding of the role of apoptosis in the
      pathophysiology of liver diseases and may allow therapeutic modulation of this
      process.

PMID- 11232195
TI  - The cell and molecular biology of hepatic fibrogenesis. Clinical and therapeutic
      implications.
AB  - Much has been learned in the past 2 decades about the cellular and molecular
      mechanisms underlying hepatic fibrogenesis and about potential therapeutic
      approaches in patients with liver disease. The central event in fibrogenesis
      seems to be the activation of hepatic stellate cells. Stellate cell activation is
      characterized by several important features, including enhanced matrix synthesis
      and a prominent contractile phenotype, processes that probably contribute to the
      physical distortion and dysfunction of the liver in advanced disease. It is
      important to emphasize that the factors controlling activation are multifactorial
      and complex. The extracellular matrix is a dynamic, active constituent of the
      fibrogenic response and undergoes active remodeling, including synthesis and
      degradation. Effective therapy for hepatic fibrogenesis will probably also be
      multifactorial, based on the basic mechanisms underlying the fibrogenic process.
      The most effective therapies will probably be directed at the stellate cell.
      Approaches that address matrix remodeling (i.e., by enhancing matrix degradation
      or by inhibiting factors that prevent matrix breakdown) may be effective.

PMID- 11232196
TI  - Mechanisms of cholestasis.
AB  - From the multiple mechanisms of cholestasis presented in this article, a unifying
      hypothesis may be deduced by parsimony. The disturbance of the flow of bile must
      inevitably lead to the intracellular retention of biliary constituents.
      Alternatively, the lack of specific components of bile unmasks the toxic
      potential of other components, as in the case of experimental mdr2 deficiency. In
      the sequence of events that leads to liver injury, the cytotoxic action of bile
      salts is pivotal to all forms of cholestasis. The inhibition of the bsep by
      drugs, sex steroids, or monohydroxy bile salts is an example of direct toxicity
      to the key mediator in canalicular bile salt excretion. In other syndromes, the
      dysfunction of distinct hepatocellular transport systems is the primary
      pathogenetic defect leading to cholestasis. Such dysfunctions include the genetic
      defects in PFIC and the direct inhibition of gene transcription by cytokines.
      Perturbations in the short-term regulation of transport protein function are
      exemplified by the cholestasis of endotoxinemia. The effect of bile salts on
      signal transduction, gene transcription, and transport processes in hepatocytes
      and cholangiocytes has become the focus of intense research in recent years. The
      central role of bile salts in the pathogenesis of cholestasis has, ironically,
      become all the more evident from the improvement of many cholestatic syndromes
      with oral bile salt therapy.

PMID- 11232197
TI  - Liver injury in alpha 1-antitrypsin deficiency.
AB  - Alpha 1-antitrypsin deficiency is the most common genetic cause of liver disease
      in children. It is also associated with chronic liver disease, hepatocellular
      carcinoma, and pulmonary emphysema in adults. Liver injury is caused by
      hepatotoxic effects of retention of the mutant alpha 1-antitrypsin molecule
      within the endoplasmic reticulum of liver cells, and emphysema is caused by
      uninhibited proteolytic damage to elastic tissue in the lung parenchyma. Recent
      studies of the biochemistry and cell biology of the mutant alpha 1-antitrypsin
      molecule have led to advances in understanding susceptibility to liver injury and
      in developing new strategies for prevention of both liver and lung disease.

PMID- 11232198
TI  - Iron-induced liver injury.
AB  - Iron, either in the form of heme or non-heme compounds, is essential to life, but
      it can also pose serious health risks. The liver is a principal target for iron
      toxicity because it is chiefly responsible for taking up and storing excessive
      amounts of iron. The major hepatic toxicities of iron overload include damage to
      multiple cell types (hepatocytes, Kupffer cells, hepatic stellate cells) and to
      multiple subcellular organelles (mitochondria, lysosomes, and smooth endoplasmic
      reticulum). Heavy iron overload, as occurs in primary (hereditary) or secondary
      forms of hemochromatosis, may cause cirrhosis, liver failure, and hepatocellular
      carcinoma. In addition, iron has been shown to be a contributory factor in the
      development or progression of alcoholic liver disease, nonalcoholic liver
      steatohepatitis, chronic viral hepatitis, prophyria cutanea tarda, and, perhaps,
      in alpha 1-antitrypsin deficiency and end-stage liver disease, regardless of
      cause.

PMID- 11232199
TI  - Mechanisms of autoimmune liver disease.
AB  - Several lines of evidence suggest that autoimmune hepatitis and primary biliary
      cirrhosis are autoimmune diseases. This article discusses both the immunologic
      mechanisms of liver injury and the mechanisms of cell injury mediated by
      lymphocytes. This article also reviews the proposed immunopathogenesis of
      autoimmune hepatitis and primary biliary cirrhosis.

PMID- 11232200
TI  - Mechanisms of ascites formation.
AB  - Ascites is the most common complication of cirrhosis. It is associated with
      profound changes in the splanchnic and systemic circulation and with renal
      abnormalities. The development of ascites is related to the existence of severe
      sinusoidal portal hypertension that causes marked splanchnic arterial
      vasodilation and a forward increase in the splanchnic production of lymph.
      Splanchnic arterial vasodilation also produces arterial vascular underfilling,
      arterial hypotension, compensatory activation of the RAAS, SNS, and AVP, and a
      continuous sodium and water retention, leading to ascites formation. Now,
      therefore, the splanchnic arterial circulation, rather than the venous portal
      system, is believed to be involved in the pathogenesis of ascites formation.

PMID- 11232201
TI  - Pathogenesis of hepatic encephalopathy.
AB  - Hepatic encephalopathy is considered to be a reversible metabolic encephalopathy,
      which occurs as a complication of hepatocellular failure and is associated with
      increased portal-systemic shunting of gut-derived nitrogenous compounds. Its
      manifestations are most consistent with a global depression of CNS function,
      which could arise as a consequence of a net increase in inhibitory
      neurotransmission, due to an imbalance between the functional status of
      inhibitory (e.g., GABA) and excitatory (e.g., glutamate) neurotransmitter
      systems. In liver failure, factors that contribute to increased GABAergic tone
      include increased synaptic levels of GABA and increased brain levels of natural
      central benzodiazepine (BZ) receptor agonists. Ammonia, present in modestly
      elevated levels, may also augment GABAergic tone by direct interaction with the
      GABAA receptor, synergistic interactions with natural central BZ receptor
      agonists, and stimulation of astrocytic synthesis and release of neurosteroid
      agonists of the GABAA receptor. Thus, there is a rationale for therapies of HE
      that lower ammonia levels and incrementally reduce increased GABAergic tone
      towards the physiologic norm.

PMID- 11232202
TI  - Hepatorenal syndrome.
AB  - Hepatorenal syndrome is a functional renal failure that occurs in cirrhotic
      patients with advanced liver disease and ascites. The diagnostic criteria and
      clinical types of this syndrome have recently been revised. Hepatorenal syndrome
      is caused by marked hypoperfusion of the kidney as the result of renal
      vasoconstriction, which is thought to be the extreme manifestation of an
      underfilling of the arterial circulation. This circulatory dysfunction is the
      consequence of arterial vasodilation in the splanchnic circulation. Liver
      transplantation is the best treatment for HRS, but its applicability is low
      because of the short survival of these patients. New therapies, such as the use
      of systemic vasoconstrictors or TIPS, seem promising, but prospective
      investigations are needed to delineate their role in the management of cirrhotic
      patients with HRS.

PMID- 11232203
TI  - Structure recapitulates function.

PMID- 11232204
TI  - A comparison of hemodynamic changes during the transition from mechanical
      ventilation to T-piece, pressure support, and continuous positive airway pressure
      in canines.
AB  - The immediate transition from positive pressure mechanical ventilation to
      spontaneous ventilation may generate significant cardiopulmonary hemodynamic
      alterations based on the mode of weaning selected, particularly in individuals
      with preexisting cardiac dysfunction. The purpose of this study was to compare
      hemodynamic responses associated with the initial transition to 3 modes of
      ventilator weaning (spontaneous ventilation/T-piece, pressure support [PS], and
      continuous positive airway pressure [CPAP]). Right ventricular hemodynamic
      responses were evaluated with a thermodilution pulmonary artery catheter; while
      left ventricular hemodynamic responses were measured by a transducer-tipped
      Millar catheter and conductance catheter. Two groups of canines were studied.
      Group 1: normal biventricular function (n = 10) and group 2: propranolol-induced
      biventricular failure (n = 10). Dependent variables were measured at baseline on
      controlled mechanical ventilation (MV) and following the initial transition to
      each of 3 randomized spontaneous ventilatory conditions: T-piece, PS 5 cmH2O, and
      CPAP 5 cmH2O. Both groups significantly increased cardiac output in response to T
      piece. Right ventricular stroke work was also significantly increased with T
      piece and CPAP in both groups of subjects. Left ventricular response depended on
      baseline ventricular function. Baseline ventricular function influenced
      hemodynamic response to the immediate transition from mechanical to spontaneous
      ventilation. There were also differential hemodynamic responses based on the
      ventilatory mode. Consideration of baseline cardiac function may be an important
      factor in the selection of an appropriate mode of spontaneous ventilation
      following controlled MV.

PMID- 11232205
TI  - A historical perspective on the discovery of adenyl purines.
AB  - In 1929, Drury and Szent-Gyorgyi described the effects of a simple extract of
      heart muscle and other tissues on the mammalian heart. This extract was
      identified as adenylic acid and found to have profound effects on the
      cardiovascular system. The discovery and identification of adenyl purines and
      their effects on the cardiovascular system has now extended to other biological
      functions such as neurotransmission, neuromodulation, and endocrine/exocrine
      secretory functions and beyond. This review examines the history of the discovery
      and identification of the many roles played by adenyl purines in regulation of
      physiological homeostasis.

PMID- 11232206
TI  - Behavioral effects of transient cerebral ischemia.
AB  - CA1 neurons in the hippocampus, a brain structure involved in learning and
      memory, are selectively vulnerable to ischemic effects. In this study, the
      authors examined if duration of ischemia is directly related to extent of CA1
      damage and degree of spatial learning deficit. Adult female Wistar rats received
      either 5-min or 10-min ischemia or sham surgery. Following recovery, rats were
      tested in the Morris water maze. Histological analysis showed moderate cell loss
      in CA1 (31%) and CA3 (12%) and minimal cell loss in CA2 (4%) with 5-min ischemia.
      Increased cell loss was seen in CA1 (68%), CA2 (16%), and CA3 (23%) with 10-min
      ischemia. Behavioral testing revealed that animals with 10-min ischemia have
      greater spatial learning deficits and they remain impaired across the test days
      compared to the 5-min ischemic group. Furthermore, degree of CA1 cell loss
      accounted for approximately 45% of the variance in spatial learning deficits in
      the ischemic group. The authors conclude that cell loss is largely confined to
      CA1 region in rats who received 5 and 10 min of ischemia and that increased
      ischemic duration results in persistent learning deficits in female rats; also,
      the degree of behavioral impairment is related to extent of CA1 cell loss.

PMID- 11232207
TI  - Cytokines and the anorexia of infection: potential mechanisms and treatments.
AB  - Anorexia during infection is thought to be mediated by immunoregulatory cytokines
      such as interleukins 1 and 6 and tumor necrosis factor. This article reviews the
      potential mechanisms of action by which these cytokines are thought to suppress
      food intake during infection and examines the proposition that blocking of
      cytokine activity might be one approach to improving food intake of the infected
      host.

PMID- 11232208
TI  - Effects of environment on enhancing functional plasticity following cerebral
      ischemia.
AB  - Given the brain's capacity to recover from injury, plasticity may be enhanced
      following cerebral ischemia through environmental manipulation. Thus, the purpose
      of this study was to (1) determine the effects of early exposure to an enriched
      environment following ischemia on functional plasticity and (2) examine the
      relationship between morphological and behavioral plasticity. Adult female rats
      (n = 38) were divided into ischemia and control groups. Each group was further
      randomized to either standard (SC) or enriched conditions (EC). After 4 days of
      environmental exposure, rats were tested for 6 days in the water maze. Control
      and ischemia rats exposed to EC have increased total dendritic length (P < 0.05)
      as well as increased number of dendritic segments in the apical (P < 0.05) region
      of the hippocampal area compared to those housed in SC; furthermore, increased
      dendritic spine density in the apical (P < 0.05) region was also seen. Behavioral
      testing showed that ischemia rats exposed to SC have longer swim latencies (P <
      0.05) and greater directional heading errors (P < 0.05) than ischemic rats
      exposed to EC; the latter group performed similar to controls. It is concluded
      that EC may be a potentially useful therapy in the recovery of spatial memory
      impairments seen after ischemia.

PMID- 11232209
TI  - Metabotropic glutamate receptor 1A: review.

PMID- 11232210
TI  - Defining and measuring balance in adults.
AB  - The ability to maintain balance is often taken for granted, yet it is the
      foundation for mobility and overall functional independence throughout the life
      span. The purpose of this article is to define balance, review the components of
      balance, and describe common instruments used to measure balance. Clinical
      screening instruments, functional performance tests, and technological measures
      of balance are reviewed addressing their uses, strengths, and limitations.

PMID- 11232211
TI  - Moving biological nursing science into the new millennium.

PMID- 11232212
TI  - The effect of familiarity on distraction and single cue use after hippocampal
      damage.
AB  - Spatial disorientation frequently occurs in conditions such as Alzheimer's
      disease that damage the hippocampus, a brain structure necessary for learning and
      memory. Use of a single cue to mark a submerged escape platform in the Morris
      water test can reduce spatial disorientation in rats. If the cue used is a
      familiar one, disoriented rats perform the wayfinding task as well as control
      animals. However, in a real-world environment, cues rarely occur alone. This
      study examined whether rats with bilateral hippocampal lesions familiar with a
      cue performed the Morris water test as well as controls and faster than lesioned
      rats unfamiliar with the cue when a distracter was present. Bilateral
      electrolytic lesions were made in male rats that had received either familiarity
      with a cue or handling only. Familiar lesioned rats were introduced to the
      distracter on test days 1 (FB1) or 3 (FB3), and unfamiliar lesioned rats on day 3
      (UB3). No significant differences were found for FB1 or FB3 rats and their
      respective controls. FB1 rats increased mean swim times on day 1 compared to
      preoperative day 4 (16.44 +/- 4.3 vs. 4.06 +/- 2.1 s, respectively, p < 0.03) but
      quickly adapted to the distracter. FB3 rats were slower than FB1 rats on day 3
      (6.81 +/- 1.0 vs. 4.56 +/- 0.3 s, respectively, p < 0.05). UB3 rats were impaired
      on the task compared to FB1 rats on days 3-7 (p < 0.05). These findings suggest
      that cue familiarity is effective in the presence of a distracter and that the
      response of disoriented rats to a distracter is influenced by the amount of prior
      experience with the cue.

PMID- 11232213
TI  - The role of the pulmonary afferent receptors in producing hemodynamic changes
      during hyperinflation and endotracheal suctioning in an oleic acid-injured animal
      model of acute respiratory failure.
AB  - The purpose of this study was to examine the role of the pulmonary afferent
      receptors in producing hemodynamic changes during hyperinflation and endotracheal
      suctioning (ETS) in an oleic acid-injured animal model of acute respiratory
      failure. Previous investigations of hyperinflation as a method to prevent hypoxia
      induced sequelae of ETS have demonstrated unrecognized hemodynamic consequences.
      In this within-subject, repeated-measures study, instrumented, oleic acid-injured
      dogs had continuous measurements of heart rate (HR), mean aortic blood pressure
      (MAP), left ventricular pressure (Plv), pulmonary artery pressure (Ppa), right
      ventricular afterload (Ppa(tm)), right atrial pressure (Pra), and right
      ventricular filling pressure (Pra(tm)) during hyperinflation and ETS when the
      vagi were intact and after the pulmonary branches of the vagus nerves had been
      severed. After severing the vagi, MAP and Plv were decreased and HR and Ppa were
      increased. With the vagi severed, there was less variation in MAP and Ppa but
      increased variation in HR. These findings suggest that vagally mediated reflexes
      from the lungs produce some, but not all, of the hemodynamic effects associated
      with hyperinflation and ETS. Continued research is necessary to discover a method
      of hyperoxygenation and suctioning that does not produce potentially harmful
      hemodynamic effects.

PMID- 11232214
TI  - Negative life experiences, depression, and immune function in abused and
      nonabused women.
AB  - Abuse of women by their intimate partner is a staggering national problem. Abused
      women have a higher number of medically unexplained somatic symptoms, more
      functional disability, a lower self-rating of general health, and higher health
      care utilization when compared to nonabused women. The authors' purpose in this
      study was to examine differences in occurrences of negative life experiences,
      level of depression, and T-cell function between abused and nonabused women. The
      sample consisted of abused women (n = 12) and nonabused women (n = 12).
      Hypotheses tested were (1) abused women will have more negative life experiences
      than nonabused women, (2) abused women will have higher levels of depression than
      nonabused women, and (3) abused women will have reduced T-cell function compared
      to nonabused women. A cross-sectional cohort design was used to compare
      differences in negative life experiences, levels of depression, and T-cell
      function. Independent sample t-tests were performed comparing the abused versus
      nonabused women on the dependent measures. Significant differences were found
      between the groups for negative life experiences (LES; t = 2.29, p < 0.05), level
      of depression (BDI; t = 3.48, p < 0.01), and T-cell function (TMR; t = -5.62, p <
      0.01). These findings are descriptive and do not establish causal links. However,
      this is an inquiry into the psychological and biobehavioral responses of women
      experiencing abuse and their potential health problems. The study shows that
      abused women reported more negative life experiences, experienced higher levels
      of depression, and experienced lower T-cell function when compared with nonabused
      women.

PMID- 11232216
TI  - Measurement of the renin-angiotensin system in heart failure.
AB  - Angiotensin II (ANG II), the effector hormone of the renin-angiotensin system
      (RAS), has been implicated in the pathophysiology and progression of heart
      failure. Therefore, the measurement of ANG II has become important to
      characterize the role of this neurohormone in heart failure. However, because ANG
      II has been difficult to measure, other components of the RAS have been measured
      to characterize ANG II production. The RAS components (e.g., renin, angiotensin I
      converting enzyme [ACE], angiotensin II) have been measured with a variety of
      techniques. In this review, RAS physiology and the techniques used to measure the
      RAS components are discussed. In addition, the advantages and disadvantages of
      the RAS measurement methods are described.

PMID- 11232215
TI  - The effects of norepinephrine infusion on the circulating lymphocyte counts of
      post-open heart surgery patients.
AB  - In this retrospective study employing chart reviews, 75 open heart surgery
      patients (OHSPs) were divided into 3 groups of 25 patients. Group 1 received no
      intravenous (i.v.) norepinephrine (NE) after surgery. Group 2 and group 3
      received a minimum of 0.028 mcg/kg/min of i.v. NE for 6-24 h and greater than 24
      h, respectively. In the 3 groups, preoperative lymphocyte counts were compared to
      counts obtained on postoperative days 1 and 2. The results showed lower
      lymphocyte counts on postoperative day 2 in group 3 subjects, who received NE for
      24 h or more, compared to subjects of the other groups who received no NE or 6-24
      h of NE (p < 0.05). There was also evidence that preoperative use of beta
      blocking agents significantly affected the change in lymphocyte counts from day 1
      to day 2 in both groups receiving NE. Furthermore, postoperative infections were
      more prevalent in group 3 than the other 2 groups (p < 0.05). The lower
      lymphocyte counts and higher infection rate, however, may be linked to lower
      postoperative blood pressure and increased number of intensive care unit days in
      group 3. Further investigation is warranted to elucidate the effects of i.v. NE
      administration on the lymphocyte counts of OHSPs and to reduce infections in
      those receiving NE.

PMID- 11232217
TI  - Basic science research in pain.
AB  - Pain is not simply a physiologic event, but a dynamic process that involves
      continuous interaction among complex systems. Nurses have the unique disciplinary
      background to envision the pain process within the context of the whole dynamic
      human being. Understanding the human condition in this holistic manner prepares
      nurses to develop clinically relevant research questions. Many of these research
      questions can best be answered initially through basic science research. Basic
      science research by a nurse will be distinct from other disciplines from the
      inception of the hypothesis through the conclusions drawn to the delineation of
      areas for further research. This article provides a few examples of basic science
      research in the area of pain by nurse researchers. The research includes both
      cellular and animal models and describes the relationship of the research to
      clinical practice. Patient care will ultimately benefit from clinically relevant
      research whether the methodology used is basic science or other methods.

PMID- 11232218
TI  - How enteral feeding options influence corticosterone patterns in rats.
AB  - Even with all the nutritional research conducted to date, it is not clear which
      enteral nutrition delivery and composition options are most physiologically
      sound. Glucocorticoid temporal patterns are reported to be shifted or disrupted
      with restricted feeding schedules, but because of intermittent sampling, temporal
      patterns have not been completely depicted. The purpose of this study was to
      characterize corticosterone temporal patterns while systematically varying
      selected enteral feeding options in a well-established nutritional animal model.
      A 2 x 2 x 2 x 2 randomized block experimental design was used in which enteral
      feeding schedules, delivery methods, kilocalorie levels (kcal), and fiber
      contents were systematically varied in rats (n = 80), and plasma corticosterone
      was measured by 125I radioimmunoassay. Blood samples were drawn hourly over 24 h.
      With cosinor analysis, 24-h and 12-h corticosterone rhythmic components were
      tested in each feeding group. Five of 16 feeding groups had a significant (p < or
      = 0.05) 24-h rhythmic component, and 3 more showed a trend (p > 0.05 < 0.10); 7
      of these groups were on 24-h feeding schedules. When rhythmic components were
      detectable, groups receiving high-fiber formula displayed more uniform rhythm
      characteristics than did no-fiber groups. Only 1 group had a significant 12-h
      rhythmic component, and 1 showed a trend. Both were on 12-h, high-fiber
      restricted kcal feedings. In this small animal sample, no one enteral feeding
      option guaranteed a 24-h corticosterone pattern. The option coming closest was
      formula delivered on a 24-h schedule. This temporal pattern is one aspect to
      consider in enteral nutrition. The underlying mechanisms have yet to be
      elucidated.

PMID- 11232219
TI  - Web-based continuing medical education. (II): Evaluation study of computer
      mediated continuing medical education.
AB  - BACKGROUND: Over the years, various distance learning technologies and methods
      have been applied to the continuing medical education needs of rural and remote
      physicians. They have included audio teleconferencing, slow scan imaging,
      correspondence study, and compressed videoconferencing. The recent emergence and
      growth of Internet, World Wide Web (Web), and compact disk read-only-memory (CD
      ROM) technologies have introduced new opportunities for providing continuing
      education to the rural medical practitioner. This evaluation study assessed the
      instructional effectiveness of a hybrid computer-mediated courseware delivery
      system on dermatologic office procedures. METHODS: A hybrid delivery system
      merges Web documents, multimedia, computer-mediated communications, and CD-ROMs
      to enable self-paced instruction and collaborative learning. Using a modified
      pretest to post-test control group study design, several evaluative criteria
      (participant reaction, learning achievement, self-reported performance change,
      and instructional transactions) were assessed by various qualitative and
      quantitative data collection methods. RESULTS: This evaluation revealed that a
      hybrid computer-mediated courseware system was an effective means for increasing
      knowledge (p < .05) and improving self-reported competency (p < .05) in
      dermatologic office procedures, and that participants were very satisfied with
      the self-paced instruction and use of asynchronous computer conferencing for
      collaborative information sharing among colleagues.

PMID- 11232220
TI  - Commercial support and the quandary of continuing medical education.
AB  - Commercial funding is a major source of financial support for the continued
      development and conduct of continuing education activities for physicians.
      However, we are again beginning to see challenges about who really controls these
      activities. Questions are being raised about the ethical behavior of physicians,
      sponsors, and grantors as they relate to compliance with the Standards for
      Commercial Support and other related documents. The Accreditation Council for
      Continuing Medical Education, grantors, providers, and physicians are challenged
      to help each other to comply with the intent, as well as the letter, of the
      documents. Without an immediate change, the cynicism of the public and the press
      may begin to drive outside forces to put into place and enforce policies that
      would be to the detriment of all interested parties.

PMID- 11232222
TI  - When disruptive approaches meet disruptive technologies: learning at a distance.
AB  - Toward the end of creating educational programs that provide both success in and
      access to learning, continuing medical education is challenged to consider new
      perspectives on learning and the incorporation of instructional technologies for
      teaching.

PMID- 11232223
TI  - Assessment of online continuing dental education in North Carolina.
AB  - BACKGROUND: Dental professionals are discovering the unique advantages of
      asynchronous lifelong learning through continuing dental education (CDE)
      opportunities offered online. The purpose of this study was to evaluate both the
      process and outcomes of online CDE in North Carolina. The assessment was designed
      to provide a better understanding of practicing dental professionals experiences
      with online CDE and to determine the effectiveness of this learning strategy.
      METHODS: Dental professionals from four North Carolina Area Health Education
      Centers regions evaluated two pilot online CDE modules in 1998. Thirty-one
      participants were recruited and subsequently enrolled with 23 completing at least
      one module. Each module included objectives, a multiple-choice pretest,
      interactive core material, and a post-test. Participants completed three online
      surveys measuring individual demographics and computer skill level, module
      design, and use and overall reaction to online learning. RESULTS: Most
      participants agreed that the modules were comprehensive, were pleasing in
      appearance, provided clear instructions, provided adequate feedback, and were
      easy to navigate. Most participants agreed that knowledge of the material
      increased. This was validated by a significant increase in mean pre- to post-test
      scores (p = .0001). Participants agreed that convenience was a definite
      advantage, and they would choose online courses again to meet their CDE needs.
      The least-liked aspects included technical and formatting issues. IMPLICATIONS:
      Participants were enthusiastic about online learning and learned effectively with
      this teaching strategy, but desired much more interactivity than existed in the
      current design.

PMID- 11232224
TI  - Identifying educational influentials for formal and informal continuing medical
      education in the province of British Columbia.
AB  - BACKGROUND: The objective of this study was to identify physicians in the
      province of British Columbia (BC) who are perceived by their colleagues to be the
      most educationally influential. METHODS: A cross-sectional study using a
      previously validated survey tool was mailed to a randomly selected sample of 2300
      BC registered primary care physicians. Follow-up mailings were sent to
      nonresponders. RESULTS: The survey response rate was 53%. A list of 375
      educationally influential physicians (EIs) was proportionately determined and
      tabulated by region. IMPLICATIONS: The top 5% of provincial EIs were identified
      to serve as a resource for formal and informal continuing medical education
      (CME). Their names will be brought forward in response to selected requests for
      CME speakers.

PMID- 11232225
TI  - Educational skills and knowledge needed and problems encountered by continuing
      medical education providers.
AB  - BACKGROUND: The objective of this study was to identify the training needs and
      difficulties encountered by continuing medical education (CME) providers in
      Quebec. METHODS: A questionnaire comprised of open-ended and closed questions was
      sent to 224 general practitioners across Quebec who organize CME meetings. To
      complement and validate the data, interviews were conducted with 18 physicians
      selected from this group, based on their years of experience with CME, and with
      the managers of two organizations involved in CME. RESULTS: The questionnaire
      response rate was 54%. Quantitative analysis was used to identify the main
      training needs expressed by CME providers affiliated with the Quebec Federation
      of General Practitioners, namely, methods for identifying needs (74%), group
      leadership techniques (69%), basic principles in adult education (69%), and
      organization of CME activities (66%). The main problems encountered by
      respondents in their duties are stimulating and maintaining the interest and
      participation of physicians in formal CME activities (52%), identifying and
      meeting physicians' educational needs (32%), and motivating physicians to get
      involved in any kind of CME initiative (18%). The interviews highlighted the wide
      disparity in the approaches used by CME providers when planning activities and
      the failure of providers to pass on relevant information to their successors.
      IMPLICATIONS: Based on the difficulties and the training needs identified, we
      were able to develop tools (structured training program, biannual newsletter,
      reference books, and resources) suited to the needs of general practitioners who
      organize CME activities.

PMID- 11232226
TI  - Web-based continuing medical education (I): field test of a hybrid computer
      mediated instructional delivery system.
AB  - BACKGROUND: The Internet and the World Wide Web (the Web) present exciting new
      possibilities for distributing educational materials at a distance and
      facilitating collaborative learning among geographically isolated physicians.
      This article provides a brief overview of the Web as an instructional delivery
      platform and discusses its strengths and weaknesses as a potential medium for
      enhancing distance learning opportunities for rural and remote physicians. It
      also describes an innovative hybrid instructional delivery model that was field
      tested by the Telemedicine Centre to determine its efficiency and effectiveness
      for providing Web-based instruction. A hybrid model merges the Web and CD-ROMs
      (compact disk read-only memory) to use several of the more valuable instructional
      components of Web-based education (i.e., multimedia, interactive forms,
      hypermedia, and computer-mediated communications). The results of the field test
      indicate that the hybrid delivery model was an efficient means for delivering
      computer-mediated continuing medical education instruction on dermatologic office
      procedures to a group of rural physicians in low telecommunication bandwidth
      regions.

PMID- 11232227
TI  - Nerve and muscle disorders and their sequelae.
AB  - A number of diseases of the nervous system, especially upper neuron lesions,
      produce ankle and foot deformities. Such deformities can be the single most
      important reason why some patients become nonambulatory. This article reviews the
      impact of upper motor neuron lesions such as traumatic brain injury, stroke,
      multiple sclerosis, neurodegenerative disorders, and low motor neuron lesions
      such as peripheral nerve injury, neuropathy, entrapment syndromes, and muscle
      diseases. This article also reviews diagnostic tests including EMG and
      nonsurgical management.

PMID- 11232228
TI  - Neuromuscular examination of the foot and ankle.
AB  - The physical examination of a patient with a neuromuscular disorder presents
      challenges that are unique to other disease entities. These injuries may affect
      motor control of the foot, and sensory and autonomic function of the foot. This
      examination depends on knowledge of normal physiology and kinematics, including
      muscle forces and the gait cycle. The authors' approach to this examination is
      conducted with emphasis on three questions that are necessary for a successful
      examination: (1) is the foot plantigrade? (2) where is the pain located? and (3)
      is the foot supple?

PMID- 11232229
TI  - Orthotic and bracing principles in neuromuscular foot and ankle problems.
AB  - The gait cycle involves a closely linked interplay among the joints of the lower
      extremity, notably the complex joints of the foot and ankle. The goals of bracing
      and orthoses in the management of neuromuscular foot and ankle problems are to
      prevent further deformity, passively correct deformity, and modulate motor tone.
      Tone-reducing AFO, in effect, improves the position of the lower extremity and
      facilitates the pathologic gait. The type of deformity present and its natural
      history by virtue of the pathologic origin must be considered when embarking on a
      conservative nonoperative course. Associated issues and thought processes are
      elaborated in the article. The biomaterials of which the orthotic brace is
      constructed, the design considerations, and expected goals of an orthosis must be
      appropriate to accommodate the pathomechanical forces encountered in the face of
      the cutaneous insensitivity. It is evident from the multiple facets of
      rehabilitative care that a team of professionals, including the orthopedist,
      physical therapist, and orthotist, along with involved health care workers, must
      be in communication and agreement to manage the challenges of these patients
      successfully.

PMID- 11232230
TI  - Cerebral palsy. Evaluation and management of equinus and equinovarus deformities.
AB  - Walking function may be enhanced by correcting equinus and equinovarus
      deformities in CP. Nonoperative management should be used in young children.
      Muscle balancing procedures, such as gastrocnemius aponeurosis lengthening,
      Achilles' tendon lengthening, and SPLATT, are particularly useful in correcting
      these deformities.

PMID- 11232231
TI  - Care of the pediatric foot in myelodysplasia.
AB  - Foot deformity is present in almost all patients paralyzed by myelomeningocele.
      This article outlines the pertinent pathoanatomy resulting in differing foot
      deformities and their effects on normal gait. Treatment of these deformities is
      discussed, and the most common deformities present for the different levels of
      paralysis are outlined. Emphasis is placed on surgical and orthotic treatments,
      which result in functional improvements for the pediatric patient with spina
      bifida.

PMID- 11232232
TI  - Treatment of the cavus foot. Deformity in the pediatric patient with Charcot
      Marie-Tooth.
AB  - The orthopedic management of foot and ankle problems associated with Charcot
      Marie-Tooth disease is becoming better understood but is still evolving. It is
      now known that Charcot-Marie-Tooth disease should be considered a spectrum of
      neurologic disorders with variable inheritance patterns, clinical course, and
      severity of deformities. Over half of the patients with Charcot-Marie-Tooth
      disease develop foot and ankle problems of which the cavovarus deformity is by
      far the commonest. Other clinical problems include weakness, parathesias, pain,
      and an unsteady gait. The cavovarus deformity seems to develop from a relative
      imbalance between the peroneus longus and tibialis anterior muscles and from an
      imbalance between the tibialis posterior and peroneus brevis muscles. Treatment
      of the cavovarus foot deformities should be individualized for each patient after
      careful preoperative evaluation. Surgery using a variety of soft tissue
      procedures and osteotomies seems to be the treatment of choice for the
      progressive cavovarus deformity in younger patients. For a patient who has
      severely rigid deformities a triple arthrodesis may be the only option but is
      considered by most to be a salvage procedure. It always should be kept in mind
      that Charcot-Marie-Tooth disease is a progressive neurologic disorder and the
      deformities can progress despite surgical intervention. Even though the results
      of treatment in this disease are difficult to evaluate because of the wide
      [figure: see text] spectrum of disease, it seems reasonable to believe that early
      surgical intervention in the flexible cavus foot can restore normal foot posture
      and help prevent or delay the need for more extensive bony procedures.

PMID- 11232233
TI  - The pathogenesis and surgical management of foot deformity in Charcot-Marie-Tooth
      disease.
AB  - The foot deformities in CMT follow certain general patterns; however, like the
      underlying motor failures that cause them, the deformities present in each
      patient are unique, and care must be individualized. There is no simple algorithm
      that can be applied to all patients. The hindfoot, forefoot, and toe deformities
      in CMT all ultimately are interconnected. As a general rule, it makes sense to
      address the plantar fascia, then proceed from the hindfoot to the forefoot in
      analyzing the deformities and in surgery. Releasing the plantar fascia may alter
      the amount of bony correction required in any concomitant hindfoot procedure.
      Likewise, only after the heel is realigned can any residual forefoot valgus be
      assessed, and a hindfoot procedure may alter the resting tension of the digital
      flexors and extensors. Finally, if a patient has purely dynamic clawtoes
      preoperatively, the toes may appear perfectly normal in the operating room with
      the ankle plantar flexed. Tightness of the flexor digitorum longus should be
      elicited by bringing the ankle up to neutral as a final check. The variety of
      foot deformities in CMT present a unique challenge to the orthopedic foot and
      ankle surgeon. It is vital for the patient and physician to remember that CMT is
      an inexorably progressive disease, and an initially good result can deteriorate
      with changing motor function. With meticulous attention to the neurologic
      examination and the balance of supple and fixed deformities in the foot, very
      satisfying outcomes usually can be obtained.

PMID- 11232234
TI  - Surgical options in the management of residual foot problems in poliomyelitis.
AB  - Although poliomyelitis is not encountered in the Western countries, it is still
      endemic in the underdeveloped world. Because the foot commonly is involved, an
      understanding of the causative factors and the available options of treatment is
      essential before surgical intervention. It is important to note that inadequate
      or improper surgical procedures potentially can lead to more disability; a well
      planned approach to the foot problem, after considering the patient as a whole
      and understanding the principles involved, is the best option.

PMID- 11232235
TI  - Surgical reconstruction of the paralytic flaccid foot.
AB  - Flaccid paralytic deformities are secondary to muscular imbalances. Conditions
      affecting the muscle itself or the neurogenic control of the muscle produce
      muscular imbalance. Once the origin of the flaccid paralytic foot is established,
      factors contributing to the deformity can be identified and addressed. It is
      imperative to understand the natural history of the underlying disorder that
      causes the deformity. The treatment of the patient with a flaccid paralysis
      depends primarily on a thorough knowledge and understanding of the normal
      function of the foot gait and secondarily on a thorough understanding of the
      natural history of the condition to be treated. A systematic, well-planned course
      of treatment, either surgical or nonsurgical, needs to be developed for each
      patient.

PMID- 11232236
TI  - Surgical reconstruction of acquired spastic foot and ankle deformity.
AB  - With the aging population and improved methods of emergency transport, the number
      of surviving stroke and brain injury patients continues to increase. Aggressive
      rehabilitation of appropriate candidates is justified. In the period of
      spontaneous recovery, efforts are made to prevent fixed contractures using
      passive mobilization, splinting, nerve blocks, and electrical stimulation. If
      deformity persists and the patient is no longer recovering, operative management
      can help alleviate the functional and hygiene problems associated with these limb
      deformities.

PMID- 11232237
TI  - Advanced techniques in foot and ankle reconstruction.
AB  - Complex deformities of the foot and ankle remain a difficult problem for even the
      most experienced surgeon. Many techniques are available to provide correction and
      no single one is appropriate for all cases. Identical deformities often can be
      treated with different techniques with equally successful outcomes. Each
      deformity is unique and the surgeon should be capable of using multiple
      techniques to provide the most appropriate treatment for the patient and the
      deformity. Simple deformities often can be handled with simple techniques but
      more complex problems often require more complex solutions. The techniques
      discussed here have worked well at the authors' institution but are undergoing
      constant reevaluation and occasional modification. It is important that the
      surgeon and the patient understand that with these techniques it is usually
      possible to provide a functional outcome but never possible to provide a normal
      foot or ankle. If appropriate goals are set, correction of these challenging
      deformities can be satisfying to surgeon and patient.

PMID- 11232238
TI  - Induction of apoptosis by the dsRNA-dependent protein kinase (PKR): mechanism of
      action.
AB  - Interferons are a family of cytokines that exerts antiviral, antitumor and
      immunomodulatory actions by inducing a complex set of proteins. One of the best
      known IFN-induced protein is the dsRNA-dependent protein kinase (PKR), that
      mediates both antiviral and anticellular activities. PKR inhibits translation
      initiation through the phosphorylation of the alpha subunit of the initiation
      factor eIF-2 (eIF-2 alpha) and also controls the activation of several
      transcription factors such as NF-kappa B, p53, or STATs. In addition, PKR
      mediates apoptosis induced by many different stimuli, such as treatment with LPS,
      TNF-alpha, viral infection, or serum starvation. The mechanism of apoptosis
      induction by PKR involves phosphorylation of eIF-2 alpha and activation of NF
      kappa B. In this way, expression of different genes is regulated by PKR. Among
      the genes upregulated in response to PKR are Fas, Bax and p53. The pathway of PKR
      induced apoptosis involves FADD activation of caspase 8 by a mechanism
      independent of Fas and TNFR. Since IFNs are used as drugs for different disorders
      such as viral infection and cancer, understanding the pathway of apoptosis
      induction triggered by PKR should be useful in the rational design of IFN
      therapies.

PMID- 11232239
TI  - A cautionary note on the use of stable transformed cells.
AB  - Gene transfection and ectopic expression is a widely used method in experimental
      biology. In the present report, we would like to point out that this approach
      may, in certain circumstances, lead to a modification of the transfected cell
      phenotype. Indeed, we observed that after transfection of bcl-2 gene in the
      neuronal PC12 cell line some of the selected clones have lost their neuronal and
      catecholaminergic characteristics, i.e. TH expression and ability to grow
      neurites in response to NGF. Thus, the resistance of some PC12-Bcl-2 clones
      against neurotoxic insults may not necessarily reflect the potential benefit
      afforded by Bcl-2 expression. We therefore encouraged authors to verify cell
      phenotype after stable transfection to avoid misinterpretation of their results.

PMID- 11232240
TI  - Prevention of nuclear localization of activated caspases correlates with
      inhibition of apoptosis.
AB  - The caspase family proteases are principal components of the apoptotic pathway.
      In this study we demonstrate that caspase-1-like proteases and interleukin-1 beta
      are important for death induced by various stimuli in cell lines, primary
      fibroblasts and primary sensory neurons. Furthermore, we show by
      immunohistochemistry that during the cell death process endogenous caspase-1-like
      proteases translocate into the nucleus. This translocation is stimulated by
      interleukin-1 receptor activation. Translocation of caspase-1-like proteases and
      cell death can be partially prevented by blocking the interleukin-1 receptor with
      the interleukin-1 receptor antagonist. This finding offers for the first time a
      mechanistic explanation for the protective effect of the interleukin-1 receptor
      antagonist against cell death. Furthermore, our data suggest that caspase-1-like
      proteases have a function in the nucleus which is necessary for completion of the
      cell death program. In cultured DRG neurons from embryonic mice the combined
      inhibition of caspases and the interleukin-1 receptor have an additive effect and
      fully prevent semaphorin III-induced neuronal death. This shows that endogenous
      caspases work together with IL-1 beta in Semaphorin III-induced neuronal death.
      We hypothesize that the cell death process involves a double activation step,
      probably including an interleukin-1 autocrine loop. This model can explain our
      finding that combined inhibition of caspases and interleukin-1 receptor is
      necessary to strongly inhibit the cell death process.

PMID- 11232241
TI  - Calmodulin-dependent and -independent apoptosis in cell of a Drosophila neuronal
      cell line.
AB  - This study was undertaken to reveal apoptotic pathways in neurons using a
      Drosophila neuronal cell line derived from larval central nervous system. We
      could induce apoptotic cell death in the cells by a Ca2+ ionophore (A23187), a
      protein kinase inhibitor (H-7), an RNA synthesis inhibitor (actinomycin D) and a
      protein synthesis inhibitor (cycloheximide). All the apoptosis induced by each
      chemical required Ca2+ ions, although the origin of Ca2+ ions were different:
      apoptosis induced by A23187 was dependent on extracellular Ca2+ ions whereas
      those by the other three chemicals utilized intracellular Ca2+ ions. Furthermore,
      different reactions to W-7, a calmodulin inhibitor, were found: W-7 prevented the
      cell death by each of the three chemicals but not by A23187. Based on the
      results, we proposed that the apoptotic pathways are classified into two types in
      individual cells. One pathway induced by H-7, actinomycin D or cycloheximide is
      calmodulin-dependent (pathway H), and another induced by A23187 is calmodulin
      independent (pathway A).

PMID- 11232242
TI  - Expression of EMAP II in the developing and adult mouse.
AB  - Endothelial monocyte-activating polypeptide II (EMAP II) is a chemoattractant for
      monocytes and granulocytes. EMAP II is translated as a precursor protein, proEMAP
      II, and is proteolytically cleaved to become the mature, biologically active
      cytokine. In this study we show that the EMAP II mRNA and the EMAP II precursor
      protein are constitutively expressed by all cell types analyzed in vitro, whereas
      the mature cytokine is only present in the supernatant of apoptotic cells. During
      mouse embryogenesis we found widespread expression of the EMAP II mRNA with
      transcripts being abundant in areas of tissue remodeling, where a large number of
      apoptotic cells could be detected by TUNEL staining. In the adult mouse, strong
      expression of the EMAP II mRNA is restricted to the brain, testis and thymus.
      Interestingly, prominent signals for EMAP II mRNA are found in local correlation
      with sites of apoptosis in thymus and testis but not in the brain. We propose
      that during development, the generation and release of the mature EMAP II may
      provide a mechanism for the recruitment of phagocytic cells to sites of
      programmed cell death. In the adult brain, the generation of mature EMAP II may
      contribute to the recruitment of monocytes and the immunosurveillance of this
      tissue.

PMID- 11232243
TI  - Inhibition of Na+/K(+)-ATPase may be one mechanism contributing to potassium
      efflux and cell shrinkage in CD95-induced apoptosis.
AB  - To investigate the involvement of K+ efflux in apoptotic cell shrinkage, we
      monitored efflux of the K+ congener, 86Rb+, and cell volume during CD95-mediated
      apoptosis in Jurkat cells. An anti-CD95 antibody caused apoptosis associated with
      intracellular GSH depletion, a significant increase in 86Rb+ efflux, and a
      decrease in cell volume compared with control cells. Preincubating Jurkat cells
      with Val-Ala-Asp-chloromethylketone (VAD-cmk), an inhibitor of caspase proteases,
      prevented the observed 86Rb+ efflux and cell shrinkage induced by the anti-CD95
      antibody. A wide range of inhibitors against most types of K+ channels could not
      inhibit CD95-mediated efflux of 86Rb+, however, the uptake of 86Rb+ by Jurkat
      cells was severely compromised when treated with anti-CD95 antibody. Uptake of
      86Rb+ in Jurkat cells was sensitive to ouabain (a specific Na+/K(+)-ATPase
      inhibitor), demonstrating Na+/K(+)-ATPase dependent K+ uptake. Ouabain induced
      significant 86Rb+ efflux in untreated cells, as well as it seemed to compete with
      86Rb+ efflux induced by the anti-CD95 antibody, supporting a role for Na+/K(+)
      ATPase in the CD95-mediated 86Rb+ efflux. Ouabain treatment of Jurkat cells did
      not cause a reduction in cell volume, although together with the anti-CD95
      antibody, ouabain potentiated CD95-mediated cell shrinkage. This suggests that
      the observed inhibition of Na+/K(+)-ATPase during apoptosis may also facilitate
      apoptotic cell shrinkage.

PMID- 11232244
TI  - Matrix metalloproteinases expression in HL-60 promyelocytic leukemia cells during
      apoptosis.
AB  - Human promyelocytic leukemia HL-60 cells have been used as a model to study both
      the expression of matrix-metalloproteinases and the mechanisms of programmed cell
      death. In the present study we examined the expression of these proteases in HL
      60 cells stimulated by different apoptotic triggers. As shown by zymography, HL
      60 cells released three major isofroms of the matrix-degrading proteases; when
      the leukemic cells were grown in serum-free conditions, as well as after
      hyperthermia and methotrexate treatment, we found a significant loss of the
      constitutive production of the 92 kDa matrixmetalloprotease, with an
      unequivocable molecular and ultrastructural evidence of programmed cell death.
      These results suggest that in HL-60 cells the expression/release of matrix
      metalloproteases can be down-regulated in the presence of the apoptotic-induced
      alterations, and that the decreased matrix-degrading capacity of this leukemic
      cell line during apoptosis may reduce its invasive potential.

PMID- 11232245
TI  - Differential expression of apoptosis-associated genes post-hepatectomy in
      cirrhotic vs. normal rats.
AB  - Liver regeneration after partial hepatectomy or liver injury is controlled by a
      wide variety of growth factors that are proven activators or inhibitors of
      hepatocyte proliferation. Liver regeneration post-hepatectomy has been proven to
      be decreased and delayed in cirrhotic vs. normal liver. Apoptosis seems to play
      an important role in cellular proliferation and in liver regeneration. Therefore,
      this study has analyzed the expression of apoptosis-associated genes following
      2/3 hepatectomy in cirrhotic vs. normal rats. Cirrhosis was induced by a weekly
      intragastric administration of CCl4 for 16 weeks followed by hepatectomy and
      histological examination of the resected liver. Rats were sacrificed at 6 h, 12
      h, 24 h, or 72 h after liver resection. The expression of proapoptotic (Bad, Bak,
      Bax) and antiapoptotic (Bcl-2, Bcl-XL) genes was analyzed by quantitative RT-PCR.
      We have observed an early increase in antiapoptotic mRNA levels and a delayed
      increase in proapoptotic mRNA levels in normal liver following hepatectomy.
      Before resection, proapoptotic mRNA levels were significantly higher in cirrhotic
      vs. normal liver. After hepatectomy, apoptotic mRNA levels were decreased and
      delayed as compared with that observed following hepatectomy in normal liver.
      These results indicate that apoptosis takes place in liver during CCl4-induced
      cirrhosis and could participate in the impaired regenerative response observed in
      cirrhotic liver.

PMID- 11232246
TI  - Rapid induction of apoptosis in human gastric cancer cell lines by sorbitol.
AB  - Most solid tumors, including gastric cancers, respond poorly to non-surgical
      treatments which are expected to induce an apoptosis-dependent involution. We
      hypothesize that the apoptotic machinery in solid tumors is either defective or
      in a suppressed condition. Overcoming the ineffective induction of apoptosis may
      improve the responsiveness of solid tumors to non-surgical treatments. Recently,
      sorbitol, a kind of hexose, has been found to be an effective inducer of
      apoptosis in HEp-2 cells. Therefore, it is of particular interest to examine the
      effect of sorbitol-treatment on gastric cancer cells. in the present study, we
      selected 4 gastric cancer cell lines which have been reported to exhibit
      different abilities in regard to apoptosis induction, and examined the effect of
      sorbitol-treatment on apoptosis induction. Within 3 hr after sorbitol-treatment,
      apoptosis was induced comparably in all cell lines examined. Cell death in MKN-1,
      MKN-28 or MKN-74 proceeded in a biphasic manner, while cell death in KATO-III was
      monophasic. The cell death partially depended on caspase activity. Treatments
      with sorbitol in combination with 12-O-tetradecanoylphorbol-13-acetate (TPA)
      markedly suppressed the apoptotic cell death, suggesting a role of protein kinase
      C-dependent process. To our knowledge, this is the most rapid induction of
      apoptosis in human gastric cancer cells reported to date.

PMID- 11232247
TI  - Rapid early onset lymphocyte cell death in mice resistant, but not susceptible to
      Leishmania major infection.
AB  - Leishmania major (Lm) infection in mice is a prototypical model for the role of
      immune deviation in disease resistance. Resistant strains of mice develop a Th1
      response to Lm infection, distinguished by secretion of IL-12 and interferon
      gamma. In contrast, susceptible strains display sustained IL-4 expression
      characteristic of a Th2 response. However, when mechanisms of cell death are
      blocked, mice display a susceptible phenotype even in the presence of a strong
      Th1 response, suggesting that cell death, and not cytokine bias, may be an
      important factor in disease resistance. Here, we investigated this hypothesis by
      comparing lymphocyte cellularity, cell death and Fas expression in resistant CBA
      and susceptible BALB/c mice during the course of Lm infection. We found that
      delayed onset of cell death and late Fas induction correlated with massive
      lymphocyte accumulation and susceptibility to leishmaniasis, while early cell
      death and rapid Fas induction occurred in resistant mice.

PMID- 11232248
TI  - Glucose transport and apoptosis.
AB  - The transport and metabolism of glucose modify programmed cell death in a number
      of different cell types. This review presents three cell death paradigms that
      link a decrease in glucose transport to apoptosis. Although these pathways
      overlap, the glucose-dependent stimuli that trigger cell death differ. These
      paradigms include glucose deprivation-induced ATP depletion and stimulation of
      the mitochondrial death pathway cascade; glucose deprivation-induced oxidative
      stress and triggering of Bax-associated events including the JNK/MAPK signalling
      pathways; and finally hypoglycemia-regulated expression of HIF-1 alpha,
      stabilization of p53 leading to an increase in p53-associated apoptosis. Several
      examples of each paradigm are presented. Future studies of glucose transport
      associated apoptotic events will allow better understanding of the role of
      cellular metabolism in programmed cell death.

PMID- 11232249
TI  - Epidemiology: theory, study design, and planning for education.
AB  - Many health professionals have received formal training in epidemiology; however,
      much of it has been limited to introductory courses at the undergraduate level.
      Further, continuing education for health professionals has focused historically
      on substantive rather than methodologic issues in epidemiology. A methodologic
      focus is recommended to improve continuing education for the health of the
      public. It is crucial to equip educators and health professionals with the
      necessary tools or resources to understand study design, conduct research,
      analyze and interpret data, and critically evaluate published research. Thus, in
      this article, a general overview of epidemiologic study design and some of the
      most common methodologic issues are presented. Issues such as confounding, effect
      modification, measurement error, and power and sample size are highlighted. A
      broader recognition of these issues by educators and health professionals may
      ultimately help to improve public health by facilitating effective educational
      interventions, proper study design, analysis, interpretation, and application of
      epidemiologic research.

PMID- 11232250
TI  - Evaluating provider prescribing practices for the treatment of tuberculosis in
      Virginia, 1995 to 1998: an assessment of educational need.
AB  - BACKGROUND: Although the use of epidemiologic studies to demonstrate learning
      needs appears to be infrequent, this study addressed the discrepancies in the
      prescribing practices for the initial treatment of tuberculosis in Virginia
      between public and private clinicians, comparing them with the treatment regimens
      recommended by the Centers for Disease Control and Prevention and the American
      Thoracic Society (CDC-ATS). METHODS: Data examined were the 1995 to 1998 reported
      cases of tuberculosis within the Commonwealth of Virginia. The study population
      consisted of 770 laboratory-confirmed tuberculosis cases, living in Virginia,
      whose isolates were tested for isoniazid susceptibility and were prescribed an
      initial drug regimen. Prevalence rates, prevalence odds ratios, and logistic
      regression were used to determine the estimated risk for receipt of the CDC-ATS
      treatment regimen. RESULTS: Of the 770 cases, 28.7% did not receive the CDC-ATS
      recommended drug regimen. Prevalence rates and odds for not receiving the
      recommended regimen were highest among persons of United States origin,
      Caucasians, females, persons under age 15, and persons from the southwest region
      of Virginia. Logistic regression indicated a slight increase in the estimated
      risk of not receiving the CDC-ATS regimen from a private physician (OR: 1.40; CI:
      0.97, 2.04) when compared to a public physician. FINDINGS: Private tuberculosis
      care providers were less compliant with CDC-ATS guidelines than public
      tuberculosis care providers. Because providers did not follow the recommended
      treatment guidelines universally, it is advised that all tuberculosis care
      providers in Virginia would benefit from increased education regarding adequate
      treatment regimens for tuberculosis and the prevention of multidrug-resistant
      tuberculosis.

PMID- 11232251
TI  - Commitment to change: a strategy for promoting educational effectiveness.
AB  - BACKGROUND: Short lecture-based courses are the most common format used in
      continuing medical education (CME) activities, yet they are relatively
      ineffective for inducing behavioral changes. This study investigates the
      effectiveness of the commitment to change strategy for identifying behavioral
      changes stimulated by such a short course. METHODS: Attendees at an annual 3-day
      lecture-based course voluntarily committed to instituting up to four changes in
      their practice. Those who made commitments were surveyed 1 month following the
      conference. RESULTS: Fifty-four percent of the intended changes had already been
      accomplished. There was no relationship between the audience's post-lecture
      evaluation scores for achieving the learning objectives compared to the number of
      changes committed to by the attendees. IMPLICATIONS: An unanticipated finding was
      the differential participation between those professions that have more autonomy
      (physicians and advanced practice nurses) versus those professions with less
      (nurses and physician's assistants). Insufficient elapsed time was the nearly
      universal limitation for initiating change. Encouraging participants to make a
      commitment to change holds a great deal of potential for both stimulating and
      documenting behavioral outcomes resulting from CME activities.

PMID- 11232252
TI  - Evaluation of a problem-based learning workshop using pre- and post-test
      objective structured clinical examinations and standardized patients.
AB  - BACKGROUND: Osteoporosis is a health care issue in which family physicians play a
      major role. Although awareness of osteoporosis is high, recent studies suggest
      that application of recent advances in its treatment to the clinical setting may
      be low. We have developed a problem-based learning intervention for osteoporosis
      in which paired rheumatologists and family physicians developed nine problem
      solving clinical scenarios. An educational matrix was used to link specific case
      scenarios with individual teaching objectives, developed via a previous needs
      assessment. Family physicians participated in the workshop, developing best
      practice responses to the clinical scenarios with a trained facilitator and
      content expert. METHODS: To assess the impact of this intervention, family
      physicians participated in a pre- and post-test evaluation, using objective
      structured clinical examinations and standardized patients. Objective structured
      clinical examination stations tested knowledge, skills, and judgment relating to
      osteoporosis with respect to risk factors, use of appropriate investigations
      including bone mineral densitometry (BMD), strategies for the prevention of
      osteoporosis (both pharmacologic and nonpharmacologic), treatment options for
      established osteoporosis (bisphosphonates and hormone replacement therapy), and
      management of recent osteoporosis fracture. Participants were evaluated using a
      predetermined score generated by their responses to objective structured clinical
      examinations and standardized patients (max. score = 101). Evaluations were
      conducted anonymously, although participants had access to their own pre- and
      post-test results for personal feedback. The impact of the workshop was assessed
      by comparing pre- and post-test responses by group, by individual, and by
      station. RESULTS: Participants demonstrated a significant improvement in their
      post-workshop scores. Of 40 participants, 26 showed improvement in score (> +10),
      13 showed modest change (+1 to +10), and 1 showed a marked decrease (> -10). The
      greatest improvements were seen in the management of the male osteoporosis
      patient, determination of risk factors for osteoporosis, and the use and
      interpretation of bone mineral densitometry. Family physicians reported general
      satisfaction with the content and format of both the workshop and the evaluation
      process. IMPLICATIONS: We conclude that this type of problem-based learning
      intervention workshop results in improved knowledge, skills, and judgment in the
      management of osteoporosis by family physicians as objectively assessed using a
      pre- and post-test format including objective structured clinical examinations
      and standardized patients.

PMID- 11232253
TI  - On-site to on-line: barriers to the use of computers for continuing education.
AB  - BACKGROUND: Continuing education/continuing medical education (CE/CME) programs
      that adopt self-directed, computer-based instruction formats via the Internet or
      CD-ROM can ease the demands placed on clinicians who are required by licensing
      boards to accumulate CE/CME credits as part of their career-long learning.
      Despite the benefits and availability of computer-based instruction, on-site
      programs still dominate current CE/CME delivery modes. In order to increase the
      use of computer-based CE/CME programs, it is important to identify the barriers
      that inhibit their use. METHOD: A survey was conducted to assess the practices,
      preferences, and barriers to use of CE/CME delivery methods among physicians,
      nurse practitioners, and physician assistants in Nevada. RESULTS: Of 3,213
      surveys sent, 1,120 were completed and returned for an overall response rate of
      35%. In-person conferences (93%) and print-based methods (66%) were the most
      frequently reported methods of acquiring CE/CME. The majority of respondents had
      access to computer-based technologies. Respondents with more years in clinical
      practice were less likely to have access to or to use computer-based
      technologies. The top three preferred CE/CME delivery modes, in rank order, were
      in-person conferences, print-based self-study, and CD-ROM. The least preferred
      method of receiving CE/CME was interactive audioconference (telephone conference
      calls). "Not knowing how" was the most frequently reported reason for not using
      the Internet for computer-based training and the second most frequent reason for
      not using a CD-ROM. IMPLICATIONS: Program planners may wish to offer training in
      new technologies during on-site conferences, provide CD-ROMs as take-home
      instructional materials, or promote technology awareness in other ways to help
      clinicians prepare for changes in the electronic delivery of health care and
      education.

PMID- 11232254
TI  - Measuring continuing medical education effectiveness and its ramification in a
      community hospital.
AB  - BACKGROUND: Is multi-interventional continuing medical education (CME) effective
      in changing one or more health care outcomes? METHOD: In a noncontrolled study
      (noncontrolled because of lack of adequate funding and support) of 328 volunteer
      recruits, a health status questionnaire including measuring serum cholesterol was
      obtained. After having identified deficiencies in the health status indicators,
      CME interventions, including didactic lectures to physicians and allied health
      professionals, announcements of data in physician lounges and departmental
      meetings, letters to physicians, and patient education, were introduced.
      Approximately 6 months after the first survey, a second survey was carried out
      and was compared with the initial data. RESULTS: Of 1,001 volunteers who were
      initially surveyed, only 328 returned for follow-up. Among seven relevant
      variables, the only change was an increase in dietary instruction by physicians
      and a reduction in serum cholesterol. CONCLUSION: In this noncontrolled multi
      interventional CME study on the treatment of hyperlipidemia, there were
      indications of improvement in physician instructions on diet and a reduction in
      serum cholesterol.

PMID- 11232255
TI  - Is now the time for continuing medical education to become continuing physician
      professional development?

PMID- 11232256
TI  - Credentialing physicians: challenges for continuing medical education.
AB  - BACKGROUND: Professionals involved in the regulation, credentialing, and
      certification of physicians around the world met in Chicago in June 2000 to
      discuss systems to ensure the competence of physicians. We learned that public
      demand for evidence of continuing competence in practice is driving the
      profession in most countries to explore new approaches to the education and
      assessment of physicians. Most groups have called the value of traditional
      continuing medical education (CME) into question and are exploring the use of
      self-directed CME methods, self-assessment, and quality improvement as the main
      instruments for maintenance of certification. It seems likely that teachers will
      be required to integrate assessment with enhancement of competencies, in much the
      same way that a coach uses an athlete's performance as a basis for continuous
      improvement. Recognizing the tough challenges ahead and the demand for CME to
      adapt to complement future plans for continuous assessment of physician
      competence, conference participants agreed to create a communication network that
      would facilitate information sharing and avoid duplication of research efforts.

PMID- 11232257
TI  - When love is just a four-letter word: victimization and romantic relationships in
      adolescence.

PMID- 11232258
TI  - Dating experiences of bullies in early adolescence.
AB  - In this study, 196 young adolescents who reported that they bullied their peers
      were identified out of a sample of 1,758 students in Grades 5 through 8. After
      selecting from the total sample a group of nonbullying youth who were matched on
      gender, school, and grade, a comparison was made of the groups' dating
      experiences, quality of friend and boyfriend or girlfriend relationships, and
      acts of physical and social aggression. The results indicated that bullies
      started dating earlier and engaged in more advanced dyadic dating than comparison
      adolescents. Bullies were highly relationship oriented, yet their views of their
      friends and boyfriends or girlfriends were less positive and less equitable than
      the comparison adolescents. Finally, bullies were more likely to report physical
      and social aggression with their boyfriends or girlfriends. Although the bullies
      reported more advanced pubertal development, this factor did not fully account
      for their dating precocity and negative romantic relationships. The results
      confirmed our hypotheses that adolescents whose peer relationships are
      characterized by bullying are at risk in their development of healthy romantic
      relationships.

PMID- 11232259
TI  - Stigmatization and the development of friendship and romantic relationships in
      adolescent victims of sexual abuse.
AB  - This study examines same- and other-sex friendship networks and perceptions of
      peer competence as functions of stigmatization, defined as shame and a self-blame
      attributional style. Fifty-six sexually abused adolescents were seen at the time
      of abuse discovery and 1 year later. Higher self-blame attributional style for
      the abuse was related to more satisfaction with other-sex friends and less
      satisfaction with same-sex friends. More shame was related to less satisfaction
      with same-sex friends and to having a larger number of other-sex friends. Higher
      self-blame attributional style was related to perceptions of poorer peer
      acceptance and close friendship and to perceptions of poorer romantic appeal.
      More shame was related to lower perceptions of peer acceptance and close
      friendship. The results support the idea that abuse victims who experience higher
      levels of shame and self-blame attributional style feel less capable of forming
      satisfying relationships with peers, friends, and potential romantic partners.

PMID- 11232260
TI  - Social network constellation and sexuality of sexually abused and comparison
      girls in childhood and adolescence.
AB  - This longitudinal study examines how childhood and early adolescent (age 6 to 15)
      peer and nonpeer social networks relate to sexual attitudes and behaviors in
      adolescence and young adulthood (age 12 to 25) for sexually abused and comparison
      girls. A large number of male peers in childhood is related to heightened sexual
      activity, sexual preoccupation, increased sexual pressure, and risky sexual
      behavior in adolescence. High-quality, female, nonpeer relationships have a
      positive effect on attitudes toward casual sex. Multiple group models illuminate
      several cross-lag group moderators: (a) Abused girls who are happier with male
      nonpeers are less preoccupied with sex; (b) abused girls who are happier with
      male peers are more likely to use birth control; and (c) abused girls who have
      early physical relationships are more likely to engage in risky sexual behavior.
      Treatment implications include monitoring the effects of low-status peer groups,
      encouraging contact with female role models, and encouraging the formation of
      high-quality relationships with male peers and nonpeers.

PMID- 11232261
TI  - Rejection sensitivity and adolescent girls' vulnerability to relationship
      centered difficulties.
AB  - Rejection sensitivity (RS)--the disposition to defensively expect, readily
      perceive, and intensely react to rejection--is a potential source of
      vulnerability for adolescent girls' relationship difficulties. RS is thought to
      develop from rejection experiences, including maltreatment. When adolescent girls
      enter romantic relationships, RS may prompt vigilance for rejection cues and
      reactions to perceived rejection that are maladaptive, including hostility. To
      preserve their romantic relationships, high RS girls may behave in ways that
      increase their risk of victimization or other negative outcomes. These claims
      were tested with longitudinal data from 154 minority, economically disadvantaged,
      middle school girls. RS prospectively predicted insecurity about a boyfriend's
      commitment and also a willingness to do things known to be wrong to maintain the
      relationship. RS predicted more physical aggression and nonphysical hostility
      during romantic conflicts. Implications for a relationship-centered approach to
      adolescent girls' characteristic vulnerabilities are discussed.

PMID- 11232262
TI  - Sexual victimization and perceptions of close relationships in adolescence.
AB  - An attachment perspective is proposed as a framework for conceptualizing the
      impact of sexual victimization on close relationships. Two studies were conducted
      to empirically examine the links between sexual victimization and perceptions of
      romantic, parental, and peer relationships. Study One included 154 undergraduate
      women, and Study Two included 48 high school seniors. In both studies,
      approximately half the women reported having experienced some form of coerced
      sexual experience. The majority were victimized by an acquaintance, and most
      victims had experienced multiple incidents. The first study found that victimized
      women had significantly more preoccupied romantic views than nonvictimized women.
      Retrospective reports indicated that women victimized in college were
      significantly more dismissing with their fathers in high school. In Study Two,
      victims reported more negative interactions with romantic partners, but no
      differences were found for romantic styles. Victims also reported more dismissing
      parental styles and more negative interactions with their fathers than
      nonvictims.

PMID- 11232263
TI  - Dating violence through the lens of adolescent romantic relationships.

PMID- 11232264
TI  - Psychometric properties of the Trauma Symptom Checklist for Children (TSCC) with
      psychiatrically hospitalized adolescents.
AB  - A sample of 119 consecutively hospitalized adolescents, including 32 sexually
      abused teenagers, was assessed with the Trauma Symptom Checklist for Children
      (TSCC). Participants also completed the Beck Depression Inventory, Symptom
      Checklist-90-Revised (SCL-90-R), Adolescent-Dissociative Experience Scale,
      Minnesota Multiphasic Personality Inventory (MMPI), Rorschach, and the Family
      Environment Scale. The reliability and validity of each of the six TSCC scales
      and four subscales was determined. Analyses suggest that the individual scales
      are reliable and significantly intercorrelated. Independent measures of
      depression, anxiety, anger, and dissociation typically correlated significantly
      with the reference TSCC scales, and in fact, the Posttraumatic Stress subscale
      significantly discriminated the sexually abused group from the remainder of the
      sample. These findings suggested that with a psychiatric sample, the TSCC is a
      valid measure of distress.

PMID- 11232265
TI  - The impact of DNA evidence in a child sexual assault trial.
AB  - Two experiments investigated the impact of DNA evidence in a child sexual assault
      (CSA) case involving a 6-year-old alleged victim. In Experiment 1, participants
      read criminal trial summaries of CSA cases in which only DNA evidence was
      presented, only the alleged child victim's testimony was presented, or both forms
      of evidence were presented. When DNA evidence was presented, there were more
      guilty verdicts and greater belief of the alleged victim than when only the
      alleged victim testified. In Experiment 2, DNA evidence was countered by an alibi
      witness testifying as to the defendant's whereabouts at the time of the alleged
      assault. The alibi witness reduced the influence of DNA evidence compared with
      when DNA evidence was presented without this witness. These results are discussed
      in terms of the comparative strengths of DNA evidence versus the testimony of the
      alleged victim.

PMID- 11232266
TI  - Swedish adjustable gastric band (SAGB) implanted laparoscopically in the
      treatment of morbid obesity--the first experience in Poland.
AB  - Surgical treatment of morbid obesity is a recognized method of proceedings in
      patients who did not obtain any positive results in conservative therapy. In
      October and November 1998 laparoscopic implantation of the SAGB was performed
      among ten morbid obesity patients with mean BMI of 41.9 +/- 3.6 kg/m2. It was the
      first experience in Poland. In this group we observed also non-insulin dependent
      diabetes mellitus in five, hyperlipidemia in eight and hypertension in three
      patients. In this series, there was no mortality and no perioperative morbidity.
      The mean operation time was 158 +/- 51 min. The mean hospital stay was four days
      after the operation. Median BMI reduction after four months was 4.7 +/- 1.6
      kg/m2. Parallel to the reduction in body weight, there occurred a significant
      reduction in plasma concentration of glucose (111.0 +/- 38.5 vs. 90.2 +/- 20.8 p
      < 0.01), total cholesterol (223.8 +/- 42.0 vs. 192.7 +/- 21.3 p < 0.005), and LDL
      cholesterol (140.4 +/- 34.0 vs. 121.7 +/- 25.2 p < 0.01). Hypertension was still
      observed only in one patient. Nowadays laparoscopic gastric banding represents
      the least invasive surgical treatment of morbid obesity. In our series
      laparoscopic implantation of SAGB seems to be an effective surgical method for
      the treatment of obesity. Substantial reduction in body weight was associated
      with improvement in metabolic control. Absence of mortality and morbidity is one
      of the main aims in bariatric surgery which was achieved in our study. The
      results of the present, first in Poland, preliminary study confirm previous
      observations that gastric banding is an effective treatment of obesity.

PMID- 11232267
TI  - Child maltreatment, other trauma exposure, and posttraumatic symptomatology among
      children with oppositional defiant and attention deficit hyperactivity disorders.
AB  - Consecutive child psychiatric outpatient admissions with disruptive behavior or
      adjustment disorders were assessed by validated instruments for trauma exposure
      and posttraumatic stress disorder (PTSD) symptoms and other psychopathology. Four
      reliably diagnosed groups were defined in a retrospective case-control design:
      Attention Deficit Hyperactivity Disorder (ADHD), Oppositional Defiant Disorder
      (ODD), comorbid ADHD-ODD, and adjustment disorder controls. ODD and (although to
      a lesser extent) ADHD were associated with a history of physical or sexual
      maltreatment. PTSD symptoms were most severe if (a) ADHD and maltreatment co
      occurred or (b) ODD and accident/illness trauma co-occurred. The association
      between ODD and PTSD Criterion D (hyperarousal/hypervigilance) symptoms remained
      after controlling for overlapping symptoms, but the association of ADHD with PTSD
      symptoms was largely due to an overlapping symptom. These findings suggest that
      screening for maltreatment, other trauma, and PTSD symptoms may enhance
      prevention, treatment, and research concerning childhood disruptive behavior
      disorders.

PMID- 11232268
TI  - Prediction of sexual, emotional, and physical maltreatment and mental health
      outcomes in a longitudinal cohort of 290 adolescent women.
AB  - A longitudinal study of 290 Canadian females measured factors at ages 3, 6, 9,
      and 13 that predicted emotional, physical, and sexual maltreatment occurring up
      to the age of 16. Significant factors predicting maltreatment were early
      neurological status and difficult temperament, cognitive status, maternal stress,
      chronic poverty, negative family climate, weak bonding, and family disruption.
      There was complex interplay between these factors in predicting both maltreatment
      status and poor mental health at age 17. Sexual abuse retained a significant link
      with emotional (but not conduct) problems when effects of physical and emotional
      abuse were controlled for. Adolescents with a combination of prolonged rather
      than brief sexual abuse combined with other types of abuse, with a background of
      family disruption and poverty, and child's impaired coping skills (reflecting
      poorer cognitive capacity and central nervous system problems) were most likely
      to have markedly impaired emotional functioning at age 17.

PMID- 11232269
TI  - Substantiation and early decision points in public child welfare: a conceptual
      reconsideration.
AB  - This article will overview substantiation in the context of early intervention
      decision points faced in state child welfare. The conceptual complexities
      underlying these interventions and how substantiation does or does not play a
      role in these interventions are explored. Specific attention will be given to the
      voluntary or involuntary nature of services, the availability of evidence, and
      the past or future orientation of the decision-making process. The conceptual
      consistency of recent child welfare policies will be explored, and suggestions
      for policy and research will be put forward.

PMID- 11232270
TI  - Two formats for eliciting retrospective reports of child sexual and physical
      abuse: effects on apparent prevalence and relationships to adjustment.
AB  - This study compared two common questionnaire formats for eliciting retrospective
      child abuse reports. Self-defined formats ask participants whether they were
      abused, using that term. Researcher-defined formats ask about particular abuse
      related events, allowing researchers to specify criteria for identifying abuse
      histories. Adjustment was measured by self-report inventories of depressive and
      posttraumatic symptoms and global self-esteem. Participants were 542 college
      women and men. Significantly less abuse was reported on the self- versus
      researcher-defined formats. Self-defined abuse was more frequent if participants
      met criteria for researcher-defined sexual or dual abuse versus physical abuse
      and if they reported relatively frequent childhood physical violence, severe
      sexual acts, and marginally, sexual perpetrators who were incestuous.
      Relationships of adjustment with researcher-defined versus self-defined abuse
      were stronger, and relationships between adjustment and researcher-defined abuse
      were independent of self-defined abuse. Discussion addressed methods of eliciting
      retrospective abuse histories for research and for clinical purposes.

PMID- 11232271
TI  - Factors related to mothers' perceptions of parenting following their children's
      disclosures of sexual abuse.
AB  - Predictors of parenting satisfaction and efficacy were examined in a sample of
      102 mothers of children who disclosed sexual abuse within the previous 12 months.
      Parenting satisfaction was predicted by conduct behavior problems exhibited by
      the child, social support from friends, and the use of approach coping
      strategies. Parenting efficacy was predicted by age of the child and conduct and
      sexual behavior problems exhibited by the child. Maternal history of child sexual
      abuse was not related to parenting satisfaction or efficacy. Results are
      discussed in relation to a stress-coping model of understanding mothers during
      the postdisclosure period.

PMID- 11232272
TI  - Relationships between different types of maltreatment during childhood and
      adjustment in adulthood.
AB  - There are very few research studies that have evaluated the relationships between
      multiple forms of childhood maltreatment and psychological adjustment in
      adulthood. This study evaluates the interrelationships between five different
      types of child maltreatment (sexual abuse, physical abuse, psychological
      maltreatment, neglect, witnessing family violence) in a community sample of women
      and men (N = 175). The relationships between the reported experience of these
      forms of maltreatment in childhood, family characteristics during childhood, and
      current psychological adjustment (trauma symptomatology and self-depreciation)
      were assessed. As hypothesized, family characteristics predicted maltreatment
      scores and adjustment, and maltreatment scores predicted adjustment after
      controlling for family environment. There were high correlations between scores
      on the five maltreatment scales. Results highlight the need to assess all forms
      of maltreatment when looking at relationships of maltreatment to adjustment and
      the importance of childhood familial environment for the long-term adjustment of
      adults.

PMID- 11232273
TI  - A preliminary study of a cartoon measure for children's reactions to chronic
      trauma.
AB  - Preliminary psychometric properties of a new instrument, Angie/Andy Cartoon
      Trauma Scales (ACTS), are presented. Angie/Andy features a cartoon-based
      methodology, measuring trauma-related sequelae of prolonged, repeated abuse. A
      sample of 208 children comprised intrafamilial trauma, extrafamilial trauma,
      combined trauma, and nontrauma groups. Angie/Andy demonstrated high internal
      consistency, with coefficient alphas from 0.70 to 0.95. The three trauma groups
      scored significantly higher than the nontrauma group on all scales (p's <
      0.0001). Generally, the most severely traumatized group scored significantly
      higher than the less severely traumatized groups. The number of types of violence
      exposures correlated with Angie/Andy scores from 0.55 to 0.74. The frequency and
      severity of trauma exposure correlated with Angie/Andy scores from 0.44 to 0.56.
      The Angie/Andy parent version correlated with a standardized parent scale from
      0.71 to 0.81. Parent/child agreement was significant. Angie/Andy is a promising
      tool for clinical assessment of chronic childhood abuse.

PMID- 11232274
TI  - Lymphoid development from stem cells and the common lymphocyte progenitors.

PMID- 11232275
TI  - Differential regulation of immunoglobulin gene transcription via nuclear matrix
      associated regions.

PMID- 11232276
TI  - B-cell-specific coactivator OCA-B: biochemical aspects, role in B-cell
      development and beyond.

PMID- 11232277
TI  - PU.1, a shared transcriptional regulator of lymphoid and myeloid cell fates.

PMID- 11232278
TI  - Control of lymphocyte differentiation by the LEF-1/TCF family of transcription
      factors.

PMID- 11232280
TI  - The IFN-beta enhancer: a paradigm for understanding activation and repression of
      inducible gene expression.

PMID- 11232279
TI  - Activation and repression of wingless/Wnt target genes by the TCF/LEF-1 family of
      transcription factors.

PMID- 11232281
TI  - V(D)J recombination: links to transposition and double-strand break repair.

PMID- 11232282
TI  - Nonhomologous end-joining proteins are required for V(D)J recombination, normal
      growth, and neurogenesis.

PMID- 11232283
TI  - Regulation of chromatin accessibility for V(D)J recombination.

PMID- 11232284
TI  - What prevents intermolecular V(D)J recombination?

PMID- 11232285
TI  - Demethylation and the establishment of kappa allelic exclusion.

PMID- 11232287
TI  - Differentiation, dedifferentiation, and redifferentiation of B-lineage
      lymphocytes: roles of the surrogate light chain and the Pax5 gene.

PMID- 11232286
TI  - RAG expression in B cells in secondary lymphoid tissues.

PMID- 11232288
TI  - Antibody diversification and selection in the mature B-cell compartment.

PMID- 11232289
TI  - Molecular mechanism of immunoglobulin class switch recombination.

PMID- 11232290
TI  - Molecular aspects of somatic hypermutation of immunoglobulin genes.

PMID- 11232291
TI  - Structural, biochemical, and biophysical studies of HLA-A2/altered peptide
      ligands binding to viral-peptide-specific human T-cell receptors.

PMID- 11232292
TI  - Visualizing T-cell recognition.

PMID- 11232293
TI  - Three signals and a master switch in the regulation of T-cell immunity.

PMID- 11232294
TI  - Studies on the adapter molecule LAT.

PMID- 11232295
TI  - The adapter proteins LAT and SLP-76 are required for T-cell activation.

PMID- 11232296
TI  - Notch and the CD4 versus CD8 lineage decision.

PMID- 11232297
TI  - Signaling in primary thymocytes after presentation of altered peptide ligands by
      antigen-presenting cells or MHC-peptide tetramers.

PMID- 11232298
TI  - The impact of pre-T-cell receptor signals on gene expression in developing T
      cells.

PMID- 11232300
TI  - CTLA-4--the costimulatory molecule that doesn't: regulation of T-cell responses
      by inhibition.

PMID- 11232299
TI  - The PTK-STAT signaling pathway has essential roles in T-cell activation in
      response to antigen stimulation.

PMID- 11232301
TI  - Mechanisms of self-tolerance and autoimmunity: from whole-animal phenotypes to
      molecular pathways.

PMID- 11232302
TI  - The maintenance and the activation signal of the B-cell antigen receptor.

PMID- 11232303
TI  - Inhibitory receptors and their modes of action.

PMID- 11232304
TI  - Consequences of Notch-mediated inhibition of the transcription factor E47.

PMID- 11232305
TI  - Genetic analysis of apoptotic and survival signals.

PMID- 11232306
TI  - Death and survival signals determine active/inactive conformations of pro
      apoptotic BAX, BAD, and BID molecules.

PMID- 11232307
TI  - Control of apoptosis in hematopoietic cells by the Bcl-2 family of proteins.

PMID- 11232308
TI  - RIPs: an emerging family of kinases involved in pro-inflammatory and apoptotic
      signaling.

PMID- 11232309
TI  - Receptor-mediated apoptosis in T lymphocytes.

PMID- 11232310
TI  - Role of the nuclear hormone receptor ROR gamma in transcriptional regulation,
      thymocyte survival, and lymphoid organogenesis.

PMID- 11232311
TI  - What keeps a resting T cell alive?

PMID- 11232312
TI  - Differential roles of cytokine signaling during T-cell development.

PMID- 11232313
TI  - Role of helix-loop-helix proteins in lymphocyte development.

PMID- 11232315
TI  - IL-4 signaling is regulated through the recruitment of phosphatases, kinases, and
      SOCS proteins to the receptor complex.

PMID- 11232314
TI  - Negative regulation of cytokine signaling by the SOCS proteins.

PMID- 11232316
TI  - Signaling via the IL-2 and IL-7 receptors from the membrane to the nucleus.

PMID- 11232317
TI  - Potential roles of Stat1 and Stat3 in cellular transformation.

PMID- 11232318
TI  - Innate immune induction of the adaptive immune response.

PMID- 11232319
TI  - Attenuation of tumor necrosis factor alpha gene transcription in macrophages by
      an autocrine factor.

PMID- 11232320
TI  - Mechanism of chromatin recognition and transcriptional regulation by LEF-1 and
      the Wnt/Wg-responsive LEF-1:beta-catenin complex.

PMID- 11232321
TI  - Controlling lymphopoiesis with a combinatorial E-protein code.

PMID- 11232322
TI  - HIV and SIV Nef modulate signal transduction and protein sorting in T cells.

PMID- 11232323
TI  - Transcription factor IRF-1 and its family members in the regulation of host
      defense.

PMID- 11232324
TI  - NF-kappa B activation by tumor necrosis factor and interleukin-1.

PMID- 11232325
TI  - Role of NF-kappa B in T-lymphocyte development.

PMID- 11232326
TI  - The I kappa B kinase: a master regulator of NF-kappa B, innate immunity, and
      epidermal differentiation.

PMID- 11232328
TI  - The molecular basis of B-cell lineage commitment.

PMID- 11232327
TI  - Signaling through calcium, calcineurin, and NF-AT in lymphocyte activation and
      development.

PMID- 11232329
TI  - Signal integration by transcription-factor assemblies: interactions of NF-AT1 and
      AP-1 on the IL-2 promoter.

PMID- 11232330
TI  - Structure and mechanism in NF-kappa B/I kappa B signaling.

PMID- 11232331
TI  - Structural studies of human TRAF2.

PMID- 11232332
TI  - Structural and biochemical analysis of signal transduction by the TRAF family of
      adapter proteins.

PMID- 11232335
TI  - Bi-stable transcriptional circuitry and GATA-3 auto-activation in Th2 commitment.

PMID- 11232334
TI  - Tissue-specific regulation of cytokine gene expression.

PMID- 11232337
TI  - Bias in the expression of IL-4 alleles: the use of T cells from a GFP knock-in
      mouse.

PMID- 11232336
TI  - Multiple levels of regulation of Th2 cytokine gene expression.

PMID- 11232333
TI  - Molecular basis of T-cell differentiation.
AB  - In summary, a multitude of regulatory systems are employed to cause the selective
      activation of target cytokine genes in Th1 and Th2 effector cells. These
      mechanisms involve both positive and negative regulation and employ at least
      three kinds of mechanisms. In the first, selective expression of transcription
      factors such as GATA3 in Th2 cells and the homeobox gene HLX in Th1 cells occurs,
      and appears in both cases to play a causal role. Another example of this would be
      c-maf, discovered by the Glimcher laboratory. A second mechanism is by the
      selective accumulation of protein through posttranscriptional mechanisms. Thus,
      junB accumulates in Th2 cells despite the fact that the junB mRNA levels are not
      different between Th1 and Th2 cells. Finally, the selective use of signaling
      pathways, in the case studied here MAP kinase pathways, leads to the selective
      activation of target genes. We believe that transcriptional up-regulation of rac2
      leads to the coupling of both the p38 and JNK MAP kinase pathways to the T-cell
      receptor and/or costimulatory receptors, thereby providing a lineage-specific
      signal.

PMID- 11232338
TI  - Role of B-lymphocyte-induced maturation protein-1 in terminal differentiation of
      B cells and other cell lineages.

PMID- 11232340
TI  - Ikaros chromatin remodeling complexes in the control of differentiation of the
      hemo-lymphoid system.

PMID- 11232339
TI  - The lymphochip: a specialized cDNA microarray for the genomic-scale analysis of
      gene expression in normal and malignant lymphocytes.

PMID- 11232341
TI  - Mechanisms of transcriptional regulation in lymphocyte progenitors: insight from
      an analysis of the terminal transferase promoter.

PMID- 11232342
TI  - Mechanisms of mu enhancer regulation in B lymphocytes.

PMID- 11232343
TI  - Neuroanniversaries 2000.

PMID- 11232344
TI  - Extracts from John Hennen's Principles of Military Surgery.
AB  - Born in Castlebar, County Mayo, Ireland, John Hennen graduated in Edinburgh and
      had a career as an army surgeon, serving through the Peninsular War. His
      Principles of Military Surgery reached a third edition (posthumously) in 1829;
      his views on nerve-injuries, tetanus, head-injuries and syphilis are considered
      below.

PMID- 11232345
TI  - Egas Moniz and the origins of psychosurgery: a review commemorating the 50th
      anniversary of Moniz's Nobel Prize.
AB  - Modern psychosurgery began in 1936 with the work of the Portuguese neurologist,
      Egas Moniz, who attempted to treat the symptoms of mental illness by severing
      neural tracts in the frontal lobes. This procedure eventually became widespread
      and applied to thousands of institutionalized, psychotic patients in the United
      States and other countries. Despite serious side effects associated with
      psychosurgery, the apparent importance and validity of the treatment was
      recognized in 1949 when Moniz received the Nobel Prize for his innovation.
      Psychosurgery was largely replaced by anti-psychotic drugs in the mid-1950s, and
      the procedure and its practitioners rapidly fell into disrepute. This article
      reviews Moniz's career, the factors that led up to his first clinical trials of
      frontal lobe surgery, and the circumstances that allowed psychosurgery to
      flourish in the 1940s, eventually leading to Moniz's Nobel Prize.

PMID- 11232346
TI  - NEUROwords. 8. Plasticity and neuroplasticity.

PMID- 11232347
TI  - Neurognostics: question 9: An American pathologist, physiologist, neurologist and
      poet.

PMID- 11232348
TI  - From the mind to the brain: an unusual pathway.
AB  - One of the most unrecognized aspects of Golgi's life was his deep interest in
      neuropsychiatry. From 1865 to 1868 he attended the Clinica per le Malattie
      Nervose e Mentali in Pavia directed by Cesare Lombroso, the founder of modern
      criminology. Golgi was involved in research on the etiology of psychiatric
      ailments. During this short period of time he produced significant theoretic
      advances in clinical psychiatry. However, very soon he started to criticize the
      conceptual approach as well as the nosological system proposed by his academic
      mentor. In July 1868 he left Lombroso's school in search for a more rational
      method of studying brain functions and diseases. In spite of his anatomical
      approach to the central nervous system, he always maintained curiosity in the
      phenomenology of functional and organic mental disorders. This predisposition is
      witnessed by his capability to relate clinical observations to neuropathological
      findings.

PMID- 11232349
TI  - Restoring Phineas Gage: a 150th retrospective.
AB  - September 13 1998 marked the 150th anniversary of the accident to Phineas Gage,
      one of the most famous cases of survival after massive injury to the brain, and
      certainly the most famous case of personality change after brain damage. For this
      article a sample of the current literature about Gage was examined. It was found
      that although his case is mentioned in about 60% of introductory textbooks in
      psychology, there is a good deal of inaccuracy in what has been written about
      him. Similar inaccuracy was found in a smaller sampling of the psychiatric,
      medical, physiological, linguistic, and general neuroscientific literature. The
      main basis of the inaccuracies is an ignorance or disregard of what is contained
      in the primary sources about Gage, coupled with a tendency to attribute to him
      characteristics that belong to other cases of frontal damage. The errors and
      their bases are discussed in an endeavour to restore the picture of Gage to its
      original state. The paper includes an Appendix of verbatim quotations from the
      primary sources that can be compared with the later, inaccurate renditions.

PMID- 11232350
TI  - Urbanization, place of experiment and how the electric fish was caught by Emil du
      Bois-Reymond.
AB  - Laboratories, along with the researchers, organisms, instruments, and experiments
      associated with these places of investigation, are not isolated from the world
      beyond their physical and institutional boundaries. Both laboratories and the
      cities in which they are embedded are subject to change, as was most dramatically
      apparent in their dynamic and far-reaching transformation during the industrial
      revolution of the nineteenth century. Using the example of Berlin and the
      institutionalization of experimental physiology by Emil du Bois-Reymond, in this
      paper I study experimental work on frogs and fish in order to demonstrate how a
      city and a laboratory cooperate in the production of knowledge. Emil du Bois
      Reymond's research on electric fish illustrates how an exotic organism and a
      laboratory came together in a city and how the research was driven by innovation
      and development in urban and industrial technology. Ongoing changes in the urban
      landscape entered du Bois-Reymond's workplace and became part of the material
      culture of his experimental physiology and his attempts to demonstrate that the
      electric fish discharge is fundamentally similar to the excitation of nerve and
      muscle.

PMID- 11232351
TI  - Making distinctions: the contribution of Hector Landouzy to differential
      diagnosis in relation to hysteria and epilepsy.
AB  - Hector Landouzy (1818-1864) is known for his Traite Complet de l'Hysterie (1846),
      which was crowned by the Academie de Medecine, but this work is not given much
      importance in historical accounts. It deserves more attention because it was more
      than an orthodox statement about the nature of hysteria. In the context of the
      diagnostic confusion between epilepsy and hysteria, it introduced a method of
      presenting criteria to facilitate diagnosis. An examination of French authors on
      epilepsy and hysteria in the second half of the nineteenth century suggests that
      this method probably set the example which was to be followed by later
      clinicians, including Charcot at the Salpetriere.

PMID- 11232353
TI  - Commemorating the 150th anniversary of Phineas Gage's accident.

PMID- 11232352
TI  - George Huntington (1850-1916) and hereditary chorea.
AB  - Although Huntington's disease has existed since at least the seventeenth century,
      and although several physicians provided earlier descriptions of hereditary
      chorea, Huntington's disease was not generally recognized until the classic
      description by George Huntington (1850-1916) in 1872. This paper--on the
      sesquicentennial of Huntington's birth--reviews Huntington's original and later
      contributions to the description of this disorder, his professional presentations
      and correspondence on the topic, and his publications, as well as his background,
      medical training, and clinical practice. The characteristics of Huntington's
      disease recognized by George Huntington in 1872--i.e., the distinct clinical
      profile, midlife onset, and autosomal dominant inheritance pattern--made the
      disease ideal for investigation by genetic linkage analysis a century after
      Huntington's description. Subsequent breakthroughs have identified the genetic
      defect as an unstable expanded CAG trinucleotide repeat mutation in a novel gene
      on the short arm of chromosome 4. The rapidity of recent discoveries bodes well
      for further significant progress in understanding, and hopefully treating, this
      profoundly debilitating neurodegenerative disorder.

PMID- 11232354
TI  - Historical note: "the epileptic constitution": the psychoanalytic concept of
      epilepsy.
AB  - The rise of the psychoanalytic approach to behavioral medicine in the early part
      of the 20th century created a unique concept of the nature and the aetiology of
      epilepsy based upon dynamic psychopathology. As a direct result of this a radical
      change in both medical and community perception of this condition was generated,
      and this was to persist up to and beyond the mid-century mark. This historical
      note details the adoption, and the rise and fall of this concept of "the
      epileptic constitution", and a consideration of the negative effects that flowed
      from this, permeating all areas of psychiatry, neurology and even the criminal
      justice system.

PMID- 11232355
TI  - Progressive familial intrahepatic cholestasis. Genetic basis and treatment.
AB  - Major advances in the understanding of the molecular mechanisms of bile formation
      and genetic studies of children with chronic cholestasis uncovered the molecular
      basis of PFIC. Specific defects in the FIC1, BSEP, and MDR3 genes are responsible
      for distinct PFIC phenotypes. These findings have confirmed the autosomal
      recessive inheritance of the disease and now provide specific diagnostic tools
      for the investigation of children with PFIC. This understanding should also allow
      prenatal diagnosis in the future. Identification of mutations in these genes will
      allow genotype-phenotype correlations to be defined within the spectrum of PFIC.
      These correlations performed in patients previously treated by UDCA or biliary
      diversion should identify those PFIC patients who could benefit from these
      therapies. In the future, other therapies, such as cell and gene therapies, might
      represent an alternative to liver transplantation. It remains to be determined if
      defects in the FIC1, BSEP, and MDR3 genes are responsible for all types of PFIC,
      or if other yet undiscovered genes, possibly involved in bile formation or its
      regulation, may be involved in the pathogenesis of PFIC.

PMID- 11232356
TI  - Alagille syndrome. The widening spectrum of arteriohepatic dysplasia.
AB  - Alagille syndrome was described more than 35 years ago as a genetic entity
      characterized by five major features: chronic cholestasis resulting from paucity
      of interlobular bile ducts, peripheral pulmonary stenosis, butterflylike
      vertebral arch defect, posterior embryotoxon, and peculiar facies. Recently,
      JAGGED1 has been identified as a responsible gene by demonstration of mutations
      in AGS patients. Studies of the JAGGED1 expression pattern demonstrate that minor
      features and almost all the elements in the long list of manifestations described
      in AGS patients are not coincidental. This finding suggests that the definition
      of AGS may be reconsidered in the light of JAGGED1 mutations.

PMID- 11232357
TI  - Biliary atresia. A surgical perspective.
AB  - The combination of portoenterostomy with subsequent liver transplantation is the
      treatment of choice for patients with biliary atresia. It is important, however,
      to attempt to keep the patient's own organ by continuing efforts to achieve the
      best possible results with portoenterostomy. Additional basic research, perhaps
      concerning on the role of cytokines and apoptosis in the control of biliary
      atresia, may provide insight into possible new medical strategies for treating
      patients with biliary atresia. For example, in addition to portoenterostomy,
      control of apoptosis at various cellular levels and of bile duct cell
      proliferation and maturation by manipulation of the growth factors and cytokines
      may become part of future treatment modalities. Another direction of research
      should be the control of fibrogenesis, which might be accomplished by blocking
      TGF-beta 1 and platelet-derived growth factor and by HGF gene therapy. The
      author's current strategy for surgical treatment for patients with biliary
      atresia include (1) early diagnosis, including prenatal diagnosis and broader use
      of mass screening programs, (2) hepatic portoenterostomy, without stoma
      formation; (3) close postoperative care, especially for prevention of
      postoperative cholangitis; (4) revision of portoenterostomy only in selected
      cases; (5) early liver transplantation in patients with absolutely failed
      portoenterostomy; (6) avoidance of laparotomy for the treatment of esophageal
      varices and hypersplenism; (7) consideration of exploratory laparotomy or primary
      liver transplantation for patients with advanced liver disease at the time of
      referral. The development of new treatment modalities based on the understanding
      of the pathogenesis of the disease, and especially on the biology of intrahepatic
      bile ducts and hepatic fibrosis, is essential.

PMID- 11232359
TI  - Urea cycle disorders.
AB  - Deficiency of any of the five enzymes in the urea cycle results in the
      accumulation of ammonia and leads to encephalopathy. Episodes of encephalopathy
      and associated symptoms are unpredictable and, if untreated, are lethal or
      produce devastating neurologic sequelae in long-term survivors. Although these
      disorders do not produce liver disease, the consequences of hyperammonemia
      resemble those seen in patients with hepatic failure or in a transient
      interference with the urea cycle, as seen in some forms of organic acidemias.
      Therefore, investigation for hyperammonemia in any infant or child with altered
      mental status (in the absence of obvious causes, such as trauma, infection, or
      poisoning) is essential for prompt diagnosis of urea cycle disorders and
      institution of treatment to avoid brain damage and death. This article addresses
      the function of the urea cycle and the diagnosis and management of urea cycle
      disorders.

PMID- 11232358
TI  - Nontransplant treatment of tyrosinemia.
AB  - NTBC treatment has greatly improved the survival of patients with acute
      tyrosinemia and has reduced the need for liver transplantation during early
      childhood. In patients in whom treatment with NTBC was started early in life, 2
      cases (1%) of HCC have occurred during the first year of treatment, but no
      further cases have occurred among these patients, who have been followed for up
      to 9 years. In patients with late start of NTBC treatment, there is a
      considerable risk for liver malignancy. The risk for malignancy in this group of
      patients must be evaluated on an individual basis, taking into account the
      phenotype and clinical status of the patient. Porphyric crises are not seen in
      patients who comply with the medication regimen. NTBC is a well-tolerated drug
      with few adverse effects.

PMID- 11232360
TI  - Liver disease caused by disorders of bile acid synthesis.
AB  - Bile acid synthetic defects are uncommon disorders that cause progressive
      cholestatic liver disease that is often lethal in infancy or early childhood.
      Five specific primary defects have been described. Diagnosis is based on mass
      spectrometry of urine and serum. Pathogenesis of liver injury is related to
      persistent reduction in levels of normal bile acids and accumulation of abnormal,
      potentially hepatotoxic, intermediaries. Sites of injury are the liver cell, the
      bile canaliculus, and the smallest bile ductules. The interlobular bile ducts are
      normal. The liver lesion is progressive chronic hepatitis with an especially high
      incidence of GCT in patients who present in infancy. Bile acid replacement
      therapy is usually effective in arresting the liver injury. Regression of liver
      damage has been documented during treatment of patients who were diagnosed early
      in life. Because bile acid synthetic disorders are the only cholestatic diseases
      of infancy in which GCT of hepatocytes is consistently present, the author
      suggest that the injury responsible for GCT may be specific for toxic bile acids.
      Accordingly, immaturity of the bile acid synthetic pathway may render many
      otherwise normal infants vulnerable to transient "neonatal hepatitis" with GCT in
      a broad range of cholestatic disorders.

PMID- 11232361
TI  - Viral hepatitis. From prevention to antivirals.
AB  - The challenge of viral hepatitis has been acknowledged and confronted in the last
      decade. Significant progress in prevention of infection with HAV and HBV may
      eradicate these serious infections from the United States and other parts of the
      world in the coming decades. Application of prophylactic strategies to children
      will be a major mechanism in accomplishing this task. The quest for potent
      antiviral medications continues. The next critically important development will
      be ways to prevent new HCV infections and to treat the millions of already
      infected individuals at risk for the serious consequences of this disease. For
      pediatricians, realizing these goals requires a greater understanding of
      perinatal HCV transmission, use of vaccines for prevention of viral hepatitis,
      and identification of HCV-infected children who are likely to benefit from new
      therapeutic strategies as they become available.

PMID- 11232362
TI  - Liver transplantation. The pediatric challenge.
AB  - Successful liver transplantation in a child is often a hard-won victory,
      requiring all the combined expertise of a dedicated pediatric transplant team.
      This article outlines the considerable challenges still facing pediatric liver
      transplant physicians and surgeons. In looking to the future, where should
      priorities lie to enhance the success already achieved? First, solutions to the
      donor shortage must be sought aggressively by increasing the use of from split
      liver transplants, judicious application of living-donor programs, and increasing
      the donation rate, perhaps by innovative means. The major immunologic barriers,
      to successful xenotransplantation make it unlikely that this option will be
      tenable in the near future. Second, current immunosuppression is nonspecific,
      toxic, and unable to be individually adjusted to the patient's immune response.
      The goal of achieving donor-specific tolerance will require new consideration of
      induction protocols. Developing a clinically applicable method to measure the
      recipient's immunoreactivity is of paramount importance, for future studies of
      new immunosuppressive strategies and to address the immediate concern of long
      term over-immunosuppression. The inclusion of pediatric patients in new protocols
      will require the ongoing insistence of pediatric transplant investigators. Third,
      the current immunosuppressive drugs have a long-term morbidity and mortality of
      their own. These long-term effects are particularly important in children who may
      well have decades of exposure to these therapies. There is now some understanding
      of their long-term renal toxicity and the risk of malignancy. New drugs may
      obviate renal toxicity, whereas the risk of malignancy is inherent in any
      nonspecific immunosuppressive regimen. Although progress is being made in
      preventing and recognizing PTLD, this entity remains an important ongoing
      concern. The global effect of long-term immunosuppression on the child's growth,
      development, and intellectual potential is unknown. Of particular concern is the
      potential for neurotoxicity from the calcineurin inhibitors. Fourth, recurrent
      disease and new diseases, perhaps potentiated by immunosuppressive drugs, must be
      considered. Already the recurrence of autoimmune disease and cryptogenic
      cirrhosis have been documented in pediatric patients. Now, a new lesion, a
      nonspecific hepatitis, sometimes with positive autoimmune markers, that may
      progress to cirrhosis has been recognized. It is not known whether this entity is
      an unusual form of rejection, an unrecognized viral infection, or a response to
      immunosuppressive drugs themselves. Finally, pediatric transplant recipients,
      like any other children, must be protected and nourished physically and mentally
      if they are to fulfill their potential. After liver transplantation the child's
      growth, intellectual functioning, and psychologic adaptation may all require
      special attention from parents, teachers, and physicians alike. There is limited
      understanding of how the enormous physical intervention of a liver
      transplantation affects a child's cognitive and psychologic function as the child
      progresses through life. The persons caring for these children have the difficult
      responsibility of providing services to evaluate these essential measures of
      children's health over the long term and to intervene if necessary. Part of the
      transplant physician's our duty to protect and advocate for children is to fight
      for equal access to health care. In most of the developing world, economic
      pressures make it impossible to consider liver transplantation a health care
      priority. In the United States and in other countries with the medical
      infrastructure to support liver transplantation, however, health care
      professionals must strive to be sure that the policies governing candidacy for
      transplantation and allocation of organs are applied justly and uniformly to all
      children whose lives are threatened by liver disease. In the current regulatory
      climate that increasingly takes medical decisions out of the hands of physicians,
      pediatricians must be even more prepared to protect the unique and often
      complicated needs of children both before and after transplantation. Only in this
      way can the challenges of the present and the future be met.

PMID- 11232363
TI  - Hepatocyte transplantation. Advancing biology and treating children.
AB  - Key advances over the past three decades have allowed the evolution of hepatocyte
      transplantation from its use as an experimental tool to study liver cell biology
      to the initial application as a potential treatment modality for patients with
      liver disease. Although little is known about the cellular and molecular
      mechanisms regulating the fate of transplanted cells, studies in animal models of
      liver disease clearly suggest that transplanted hepatocytes have the potential to
      repopulate diseased livers and correct metabolic defects. Based on these
      experiments, human hepatocytes have been used in the treatment of children and
      adults with metabolic disease and liver failure. In initial trials, the improved
      clinical course following hepatocyte transplantation points to a potential role
      of the technique as an adjunct to liver transplantation.

PMID- 11232364
TI  - The unique nature of the pediatric liver.

PMID- 11232365
TI  - Patient Tan revisited: a case of atypical global aphasia?
AB  - Broca's first patient presented in support of a relationship between a lesion of
      the frontal lobe and aphasia was patient Tan. Although Pierre Marie refers to
      this case as "indisputably aphasia of Broca," the clinical diagnosis of Tan's
      aphasia has not been re-examined in light of current clinical criteria.
      Superficially, the patient's extremely limited verbal output and intact
      comprehension appear to fit with the diagnosis of Broca's aphasia, but a more
      thorough examination of the onset, evolution and nature of the patient's speech
      symptoms suggests alternate interpretations. Contemporary evidence in support of
      a robust relationship between stereotypical utterances and Global aphasia
      suggests that patient Tan may have suffered from a Global rather than Broca's
      aphasia.

PMID- 11232366
TI  - Magnus Gustaf Blix (1849-1904); neurophysiological, physiological, and
      engineering virtuoso.
AB  - This paper was written to honour the 150th anniversary of the birth of Magnus
      Gustaf Blix. Blix belongs to the small group of 19th century physiologic
      neuroscientists who still regularly are cited, on account of having presented
      fundamental results. He contributed to three fields: somatic sensation, and
      visual and muscular function. He was the first to publish evidence regarding
      modality specific receptors in the skin. He extended the work of Hermann von
      Helmholtz on the optical properties of the anterior ocular chamber of living
      humans, after having constructed the necessary apparatus. He also measured the
      heat production of contracting muscles. For this purpose he constructed the
      apparatus that provided a start for A. V. Hill's Nobel Prize-winning work in the
      field. He showed for the first time that the power of muscle contractions
      depended on the length/extension of the muscle fibres. He worked on the
      possibility of muscle powered human aviation. For this purpose he constructed a
      bicycle dynamometer for measuring the maximal human power output. He was the vice
      chancellor of Lund university when he died from an acute disease in 1904 at the
      age of only 55 years.

PMID- 11232367
TI  - Solomon Carter Fuller, M.D. (1872-1953): American pioneer in Alzheimer's disease
      research.
AB  - The appointment of Alois Alzheimer to Emil Kraepelin's clinic and laboratory at
      the Royal Psychiatric Hospital, University of Munich in 1903 offered new
      opportunities for clinical and pathological studies of the brain. At the opening
      of the facility in 1904, Alzheimer selected five foreign visiting students as his
      graduate research assistants, among whom was an American, Dr. Solomon Carter
      Fuller. A glimpse of Fuller's background as an African-American (born in Liberia)
      at the turn of the century, his continuing research after leaving Germany in
      1906, and his critical view of the Alzheimer dementia entity are recounted. He
      was held in high esteem as a practicing neuropsychiatrist and teacher in the
      Boston area.

PMID- 11232368
TI  - The Tulane Electrical Brain Stimulation Program a historical case study in
      medical ethics.
AB  - In 1950 physicians at Tulane University School of Medicine began a program of
      research on the use of electrical brain stimulation that would span three decades
      and involve approximately 100 patients. Initially, electrical brain stimulation
      was used to treat of schizophrenia, but later it was applied to a variety of
      other conditions. Throughout its history the Tulane research was well publicized
      in both the professional and lay literature, and for almost twenty years, with
      rare exception, these accounts were laudatory. However, in the early 1970s this
      work began to draw sharp public criticism. Despite its public and controversial
      nature, the Tulane electrical brain stimulation program has received relatively
      little attention from historians. This review recounts the history of the Tulane
      program with particular emphasis on the ethical propriety of the work. Factors
      that shaped the historical context in which the Tulane experiments were conducted
      are discussed.

PMID- 11232369
TI  - Ragnar Granit 100 years--memories and reflections.
AB  - The Swedish-Finnish Nobel laureate Ragnar Granit, born 100 years ago, is
      commemorated in a brief article by one of his former PhD students and
      collaborators. After a short account of Granit's life and scientific career,
      special attention is given to Granit's role as a teacher in research training and
      his published thoughts on this matter, partly reflecting Granit's own experience
      as a "postdoc" in the laboratory of Sherrington (Oxford). The article includes
      personal recollections of how it was to work together with Granit in his
      laboratory.

PMID- 11232370
TI  - Epilepsy and catalepsy in Anglo-American literature between romanticism and
      realism: Tennyson, Poe, Eliot and Collins.
AB  - Epilepsy and catalepsy were not clearly separated in the minds of people in the
      early 19th century, and catalepsy may have been used as a diagnostic euphemism
      for epilepsy. Tennyson, in "The Princess" describes, under the diagnosis of
      catalepsy, probable temporal lobe epileptic dreamy states with derealization
      which serve as a metaphor of sexual and moral ambivalence, the poem's central
      theme. It seems that Tennyson knew such seizures from his own father who had been
      given a diagnosis of catalepsy. Poe gave his Berenice in the novella of the same
      title a diagnosis of epilepsy as a reason for a premature burial. However, there
      was a good deal of unlikelyhood in this, and when he came to this theme in "The
      Fall of the House of Usher" and in "The Premature Burial" he chose instead a
      diagnosis of catalepsy which fitted better with the plot. The fits of the title
      character in George Eliot's Silas Marner, diagnosed as catalepsy, would today
      rather be seen as epileptic twilight states. It would seem that this author drew
      from contemporary dictionary descriptions which described conditions similar to
      Marner's fits under the heading of catalepsy. In Eliot's "legend with a realistic
      treatment", the twilight states are a central factor in the plot and explain
      Marner's reclusion and passivity. In Poor Miss Finch by English realist Wilkie
      Collins, the post-traumatic seizures of Oscar, one of the main characters, their
      cause, their treatment with silver nitrate, and the subsequent discoloration of
      his skin are central supporting elements of a perfectly constructed plot. Collins
      gives an exact description of a right versive seizure with secondary
      generalisation, and how to deal with it. In none of these works seizures are seen
      in a negative light. They rather evoke reactions of sympathy and support.

PMID- 11232371
TI  - James Joyce: steps towards a diagnosis.
AB  - Authors whose scholarship is in the golden realm of English literature have not
      hesitated to make pronouncements on James Joyce's health. A publication in this
      genre claims he had tabes dorsalis. One feels that an authoritative comment,
      accepting or rejecting a diagnosis of neurosyphilis, should be provided by the
      Journal of the History of the Neurosciences.

PMID- 11232372
TI  - Inflammation of the mind. On the 300th anniversary of Gerard van Swieten.
AB  - History teaches that the ancient phrenitis concept has been used until the 19th
      century. After that time the concept was replaced by the word delirium. By their
      epigonic character the detailed descriptions of phrenitis by Van Swieten mark
      only the end of an uncritical use of the term. The epoch-making work of Morgagni,
      based on clinical-anatomical observations, provides a definitive insight into the
      location of the condition and into many pathologic features. Pinel is the last
      author who mentions phrenitis in a classification of diseases. After that time
      phrenitis became a vanished disease.

PMID- 11232373
TI  - NEUROwords. 9. Vater, Pacini, Wagner, Meissner, Golgi, Mazzoni, Ruffini, Merkel
      and Krause: were their nerves all on edge?

PMID- 11232374
TI  - European Federation of Neurological Societies Panel on the History of the
      Neurosciences. Report of the focussed workshop held at Lisbon on 9 September
      1999.

PMID- 11232375
TI  - "Syntonic change": a mental health perspective on avoiding the crises associated
      with change within organizations.
AB  - Historically, change within organizations has led to increased stress within the
      workforce. Organizational change is usually met with resentment and resistance
      yielding a crisis which impinges upon not only organizational effectiveness, but
      mental health as well. Most change efforts result in failure yielding dramatic
      declines in productivity, as well as accelerated attrition within the human
      resource. This paper proposes a model of "syntonic change" as a means of meeting
      both the needs of the organization to remain dynamic and flexible, and the needs
      of the workforce for a sense of trust and safety.

PMID- 11232376
TI  - The impact of parental disruption on Kuwaiti adolescents: a comparative study on
      children from intact and broken families.
AB  - Divorce, which was once a rare phenomenon in Kuwait, now occurs in nearly one
      third of all marriages. The purpose of this study was to compare the differences
      in self-esteem, locus of control, and attitude toward parents between Kuwaiti
      adolescents from divorced and intact families. The results revealed that
      adolescents from divorced families showed higher self-esteem than adolescents
      from intact families. Within the divorced families, females showed higher self
      esteem compared to males. There was no difference in locus of control between
      divorced and intact families nor were there any gender differences. Divorced
      fathers were evaluated negatively by their children whereas divorced mothers were
      evaluated positively. These data are believed to be the first of its kind from
      divorced families in Kuwait or the Middle East.

PMID- 11232377
TI  - Community crisis intervention: the Coldenham tragedy revisited.
AB  - Crisis intervention is commonly thought of as acute psychological first-aid
      applied within close temporal proximity to the precipitating event. This paper
      reports the positive effects of a comprehensive crisis intervention applied over
      three years after the precipitating event and on a "community-wide" basis.

PMID- 11232378
TI  - Victim identification and family support in mass casualties: the Massachusetts
      model.
AB  - The Aviation Disaster Family Assistance Act of 1996 requires the National
      Transportation Safety Board (NTSB), air carriers, and the American Red Cross
      (ARC) to provide an integrated family assistance center to offer support to
      family survivors of mass casualties. A central component of post-incident
      response is the timely identification of victims and their personal belongings.
      This identification process occurs through antemortem interviews with family
      survivors. ARC of Massachusetts Bay determined that ARC volunteers would not play
      a major role in conducting antemortem interviews, and deferred primary
      responsibility for this task to the Massachusetts Office of the Chief Medical
      Examiner (OCMB). This paper presents the Massachusetts model for victim
      identification and family support at the local level. The structure and services
      of this model for on-site forensic processing, the fielding of antemortem
      interviewers, and a comprehensive training curriculum in psychological trauma and
      victim identification are presented. The implications are discussed.

PMID- 11232379
TI  - Treating family survivors of mass casualties: a CISM family crisis intervention
      approach.
AB  - Critical Incident Stress Management (CISM) approaches emphasize the needs of
      families in crisis as one component of comprehensive service delivery. The need
      is particularly true for family survivors of mass casualties. This paper presents
      one CISM theoretical approach to these family survivors that is based on both the
      general principles of crisis intervention and recent findings in the field of
      psychological trauma. The model outlines three stages that many family survivors
      encounter as well as the time lines, tasks, and primary feeling states in each
      stage. Specific strategies for intervention in each stage are presented. The
      implications are discussed.

PMID- 11232380
TI  - The role of employee assistance programs in the era of rapid change in the health
      care delivery system.
AB  - With the rapid changes occurring in the American healthcare system, questions
      regarding various aspects of care have arisen. These changes have led to the need
      for individuals working within an Employee Assistance Program (EAP) to respond
      quickly and effectively to crisis situations. This article summarizes the
      different roles and responsibilities of EAP workers in the healthcare
      marketplace.

PMID- 11232381
TI  - Critical incident stress debriefing: clinical applications and new directions.
AB  - Critical Incident Stress Debriefing (CISD) was originally developed as a short
      term, group-format, preventive mental health intervention for traumatized law
      enforcement and emergency services personnel. The debriefing model has since been
      applied to a variety of clinical groups and crisis situations, correspondingly
      undergoing modifications in its structure and process. This review describes the
      CISD approach and explores some of the new directions being taken by
      practitioners of this intervention strategy. In addition, this review addresses
      some of the recent critiques of the CISD model, and makes recommendations for
      optimal utilization of this clinical tool with those populations most likely to
      benefit from it.

PMID- 11232382
TI  - Theoretical perspectives of traumatic stress and debriefings.
AB  - The purpose of this article was to attempt to identify and examine the core set
      of elements or factors which are germane to understanding the process and effects
      of traumatic stress and psychological debriefings. Before these factors are
      addressed, relevant questions regarding the nature, level of care, and
      implementation of debriefings are raised. A person-environment interactional
      model is used to explain the typologies of traumatic events and stressor
      dimensions. Factors considered fundamental to crisis response, goals common to
      debriefings, and the need to recognize the diversity of traumatic events are then
      reviewed.

PMID- 11232383
TI  - Toward a model of psychological triage: who will most need assistance?
AB  - While well developed within physical medicine, the concept of triage within
      emergency mental health is ill-defined. The purpose of this paper is to offer one
      formulation and a rudimentary set of guidelines for the process of psychological
      triage for individuals in crisis. These recommendations are unique in that they
      reflect an integration of clinical empiricism and applied physiological concepts.
      It is hoped that such an initiative will assist in the most efficient and
      effective allocation of mental health resources in acute crises, traumas,
      disasters, and even combat-related situations.

PMID- 11232384
TI  - A clinical demonstration model for assessing the effectiveness of therapeutic
      interventions: an expanded clinical trials methodology.
AB  - Both the evaluation of current treatment interventions and the innovation of new
      ones are vital to maintaining a viable clinical profession. In the field of
      psychology, however, often there are serious challenges facing these worthy
      endeavors. This article reviews several problems and limitations with evaluation
      of innovative psychotherapy treatments in clinical practice and suggests a
      strategy to overcome these. This approach, which we term the "Systematic Clinical
      Demonstration Methodology," (SCDM) combines the skills of clinicians with the
      rigors of clinical trials methods and permits concurrent clinical innovation and
      scientific evaluation. Here we suggest that the SCDM approach allows innovative
      practitioners to assist in the development and evaluation of promising clinical
      interventions by working closely with clinical trials researchers. This allows
      innovative clinicians to demonstrate new treatment approaches, while clinical
      researchers evaluate the effectiveness and safety of these interventions using
      clinical trials methods that incorporate qualitative data. We suggest that this
      approach can result in the development and evaluation of new treatment
      innovations more quickly and cost effectively than traditionally has been the
      case. In addition, some limitations commonly associated with clinical trials,
      such as not treating patients typically found in clinical practice, failing to
      treat patients with multiple disorders, or treating patients from different
      cultural or sociodemographic groups, can be more effectively addressed. Our
      experiences with using this method to evaluate different psychotherapy treatments
      for posttraumatic stress disorder are presented as an example of this new
      approach.

PMID- 11232385
TI  - Critical incident stress debriefing (CISD): a meta-analysis.
AB  - Psychological debriefings represent a genre of group crisis interventions.
      Critical Incident Stress Debriefing (CISD) represents the oldest standardized
      variation of this genre. Recent reviews have called into question the
      effectiveness of CISD. In this study 5 previously published investigations were
      meta-analyzed revealing a large effect size (Cohen's d = .86) supporting the
      notion that the CISD model of psychological debriefing is an effective crisis
      intervention.

PMID- 11232386
TI  - Critical incident stress management (CISM): the assaultive psychiatric patient.
AB  - Critical Incident Stress Management (CISM; Everly & Mitchell, 1999) is an
      integrated, multicomponent crisis intervention approach that is helpful in
      mitigating and preventing the potentially adverse consequences associated with
      critical incidents. The CISM model may serve a valuable heuristic purpose in the
      planning and development of CISM approaches in a wide variety of organizations
      and industries. This paper reports on the use of the CISM approach (Everly &
      Mitchell, 1999) as a guide or template in developing an enhanced and updated
      Assaulted Staff Action Program (ASAP; Flannery, 1998) approach to service
      delivery. ASAP is a voluntary, peer-help, CISM approach for staff who are
      assaulted by patients. The updating of its comprehensive services was
      necessitated by recent research and clinical experience on the changing nature of
      the assaultive psychiatric patient.

PMID- 11232387
TI  - Helpful and hurtful aspects of psychological debriefing groups.
AB  - Psychological debriefing groups have become one of the most common interventions
      to help people in trauma and crisis. The rapid spread of such groups makes it
      important to consider both positive and possible negative results of such groups.
      Debriefing groups provide an opportunity for normalization of a crisis
      experience. However, as with any powerful intervention, there is the danger that
      such groups may harm participants. Good leadership reduces the possibility of a
      negative outcome and requires an emphasis on the early parts of the debriefing to
      build trust and authority. This, as well as different ways of handling problems
      in the group process, are outlined. Future challenges to the genre of
      psychological debriefing are presented, including when not to use debriefing
      groups.

PMID- 11232388
TI  - Psychological autopsies for equivocal deaths.
AB  - Although in use since 1958, the term "psychological autopsy" and its constituent
      elements have yet to achieve either consensual validation or operational
      standardization. This calls into question issues of content validity and
      reliability when psychological autopsies are used in the field. This paper argues
      for a clear differentiation between psychological autopsies used subsequent to
      suicide versus equivocal deaths and for the recognition of Equivocal Death
      Psychological Autopsy as a clearly distinct form of psychological autopsy with
      its own constituent elements and training guidelines.

PMID- 11232389
TI  - Avalanches in Iceland.
AB  - This report will explain the unique nature of the two avalanche accidents at
      Suthavik and Flateyri in the western part of Iceland. The report will describe
      the difficult conditions encountered by the rescuers, the medical personnel and
      all the other people involved. Finally, the implementation of Critical Incident
      Stress Management (CISM) will be described.

PMID- 11232390
TI  - Psychopharmacology and posttraumatic stress disorder.
AB  - Posttraumatic Stress Disorder (PTSD) is a complex and challenging psychiatric
      disorder. Its more severe manifestations will require psychopharmacologic
      intervention. This paper offers guidance in the psychopharmacologic management of
      PTSD.

PMID- 11232391
TI  - Fixation of metatarsal osteotomies in the treatment of hallux valgus.
AB  - Osteotomies as a treatment for hallux valgus require careful preoperative
      planning and meticulous attention to surgical technique. The procedure selected
      should be tailored to fit the deformity. For a patient with mild hallux valgus,
      the chevron osteotomy is the most intrinsically stable of the distal osteotomies
      and has the least potential for complications. Interest in the Ludloff osteotomy
      has had a resurgence because of its improved stability compared with more
      traditional osteotomies for correction of metatarsus primus varus. This
      osteotomy, however, is less forgiving and more dependent on technique than other
      procedures. The proximal chevron osteotomy, with plantar-to-dorsal screw
      placement, is easier to perform than the Ludloff and provides excellent
      stability. Regardless of the osteotomy used, screw fixation has been shown to be
      mechanically superior to all other modes of fixation (K-wire, staples, or no
      fixation). Postoperatively, a hard-soled postoperative shoe that permits weight
      bearing on the heel and lateral foot is recommended; however, for the more
      unstable osteotomies and for those performed in patients with poor bone quality,
      a period of non-weight-bearing should be considered. Future studies with cyclic
      loading may help modify these current postoperative restrictions.

PMID- 11232392
TI  - Hypermobility of the first ray.
AB  - Hypermobility of the first ray is one of the causative components in common foot
      problems (such as hallux valgus) with a large intermetatarsal angle and
      metatarsus primus varus. Although not always associated with hallux valgus,
      hypermobility is a predisposing factor for this deformity, especially in
      conjunction with extrinsic factors, such as disruption of the plantar first
      metatarsal cuneiform ligament and tendon-muscle imbalance. Hypermobility is also
      frequently found in adolescents with hallux valgus, especially when associated
      with a large intermetatarsal angle. Motion at the first metatarsocuneiform joint
      occurs in the sagittal and transverse planes. Most studies agree that greater
      than 4 degrees and greater than 8 degrees, respectively, constitutes excessive
      motion. Clinically, hypermobility is evaluated by determining sagittal motion
      (the grasping test) and transverse motion (the clinical squeeze test) and by
      identifying signs such as the presence of a dorsal bunion, intractable plantar
      keratosis beneath the second metatarsal head, and arthritis of the first and
      second metatarsocuneiform joint. Radiographically, hypermobility is evaluated by
      measurements from the modified Coleman block test (for sagittal motion) and the
      radiographic squeeze test (for transverse motion) and by the identification of
      signs, such as cortical hypertrophy along the medial border of the second
      metatarsal shaft, a cuneiform split, the presence of os intermetatarseum, and the
      round shape and increased medial slope of the first metatarsocuneiform joint.
      Usually, treatment for hypermobility of the first ray is operative, but surgery
      is contraindicated for patients less than 20 years of age (especially when the
      epiphysis is not closed) and for patients with generalized ligamentous laxity,
      short first metatarsal, and arthritis of the hallux MTP joint. The authors'
      surgical treatment of choice is arthrodesis of the tarsometatarsal joint (as part
      of the hallux valgus correction), exostectomy, capsulorraphy, and distal soft
      tissue release to correct and stabilize the first metatarsal at the apex of the
      deformity. The authors have found it unnecessary to include the base of the
      second metatarsal. The main complications associated with the Lapidus procedure
      and its modifications are nonunion, malunion, and dorsal elevation of the first
      metatarsal. Although radiographic nonunion is the most frequent complication,
      only 25% of the patients with this condition have associated clinical findings;
      the results have been defined as good or excellent in two series. These results
      closely equal those in rheumatoid or sedentary patients managed with newer,
      modified, less traumatic techniques that stabilize the first metatarsocuneiform
      joint with screws rather than with arthrodesis.

PMID- 11232393
TI  - Hallux valgus correction by the method of Bosch: a new technique with a seven-to
      ten-year follow-up.
AB  - Subcapital osteotomy of the first metatarsal is used as the treatment of choice
      for the correction of hallux valgus. The advantages are a short operation time,
      no soft tissue procedures, secure union, avoidance of metatarsal head (MTH)
      necrosis and a varus malalignment. An alternative temporary fixation of hallux
      valgus also having an arthrosis is performed with a specially developed angle
      plate (Synthes-Stratec, Austria) with the skin incision lengthened to 1-cm.
      Adequate displacement of the MTH over the sesamoid bones provides a permanent
      satisfying result even without an operation on the abductor or the adductor. This
      article reviews 98 feet of 64 patients who were examined in a follow-up study
      from the initial 114 cases that were operated. The mean follow-up time was 8
      years and 9 months.

PMID- 11232394
TI  - Hallux valgus correction by the method of Bosch: a clinical evaluation.
AB  - Between December 1996 and February 1999, 197 operations for the correction of
      hallux valgus by the percutaneous technique of Bosch were performed in 156
      patients (41 bilateral) at the Cardinal G. Panico Hospital (Tricase, Italy). Most
      operations were performed using local anesthesia. Unsupported weight bearing was
      nearly always allowed on the first postoperative day and a simple functional
      bandage was used for six weeks. One hundred forty three patients (39 bilateral)
      were available for follow-up evaluation (182 feet) at an average follow-up of
      16.4 months. Clinical results and radiographic evaluation of these patients
      showed that 89% were fully satisfied with their result. Thus, it appears that the
      distal osteotomy of the first metatarsal using the technique of Bosch, combined,
      if necessary, with other procedures on the lateral metatarsals, is a satisfactory
      operation. Important features of this procedure include short operating time, low
      incidence of complications, and high patient compliance.

PMID- 11232395
TI  - Scarf osteotomy for correction of hallux valgus. Surgical technique and results
      as compared to distal chevron osteotomy.
AB  - With the Scarf osteotomy, a good correction of moderate hallux valgus can be
      obtained, comparable to the distal or proximal Chevron or crecentic osteotomy.
      Correction of the IMA averages between 5 degrees to 6 degrees. When used in
      combination with an adductor release and proximal phalangeal osteotomy, the
      indication can be extended to severe hallux valgus deformities as long as there
      is no arthrosis at the MTP joint. The Scarf osteotomy, however, is certainly a
      more extensive surgical procedure, with a longer learning curve than a distal
      Chevron osteotomy. With more than 1000 Scarf procedures performed, the author has
      not encountered one delayed union, even in osteoporotic bone, or an avascular
      necrosis. In two cases a stress fracture was encountered in the first 3 months
      after surgery, but these healed uneventfully with partial weight bearing for 5
      weeks.

PMID- 11232396
TI  - Scarf osteotomy for hallux valgus correction. Local anatomy, surgical technique,
      and combination with other forefoot procedures.
AB  - At first, scarf osteotomy can be technically demanding. The aim of the author has
      been to develop an efficient technique, make it easier and more accurate, and to
      achieve immediate reproducibility of results. Neither the skin incision nor the
      length of the osteotomy result in postoperative edema, whereas the strong
      fixation enables very early functional recovery. Complications are rare and
      avoidable. The sum of the scarf's advantages results in a reliable surgical
      procedure. The scarf osteotomy is extremely versatile, because it allows a wide
      range of fragment displacement. This is why the scarf is not a single osteotomy
      but several. This means its indications are broad, from mild to the most advanced
      deformities, including arthritic, juvenile, iatrogenic, and even rheumatoid
      hallux valgus. The contraindications of scarf osteotomy are a very large hallux
      valgus deformity with a very thin first metatarsal; extremely deformed MPT joint,
      and hallux valgus combined with a severe pes planus and hypermobility of the
      first metatarsal (the Lapidus procedure is preferable at this stage). Finally, we
      should remember the two following points: 1. Whatever the indication, the scarf
      first metatarsal osteotomy is only one of the four steps necessary for correcting
      hallux valgus deformity: a) MTP lateral release, b) Scarf osteotomy, c) medial
      capsulorraphy, and d) great toe proximal osteotomy. 2. The scarf is just one
      element of the different procedures, including the Weil lesser ray osteotomy,
      which allow precise forefoot management according to each static disorder. These
      techniques have very significantly extended the indications for most static
      disorders where corrective surgery preserves the joints and their mobility.

PMID- 11232397
TI  - Scarf osteotomy for correction of hallux valgus. Historical perspective, surgical
      technique, and results.
AB  - The Scarf osteotomy has proven to be a versatile and powerful procedure to
      correct various degrees of hallux valgus deformity. Through modifications of bone
      cut lengths and in combination with a phalangeal osteotomy, most hallux valgus
      deformities can be addressed. In cases of extreme hypermobility of the first ray
      or arthrosis of the first metatarsocuneiform joint, the Lapidus operation may be
      more appropriate. Hallux valgus rigidus or hallux valgus with severe rheumatoid
      joint disease usually requires alternative procedures. The results of the Scarf
      osteotomy compare favorably with the results reported for other popular bunion
      surgeries. When choosing a procedure, the clinician should consider that the
      Scarf osteotomy allows the patient to ambulate postoperatively without a cast or
      the use of crutches, to return to bathing and a closed athletic shoe in one week,
      and to have bilateral surgery, which maintains cost-effectiveness and returns the
      patient to his or her desired lifestyle more quickly. It has been said that
      surgery is both a science and an art. The author often believes that bunion
      surgery is more art than science, hence the success of so many procedures in one
      surgeon's hands and the failure in another's hands. The Scarf bunionectomy is a
      technically demanding procedure that has a large learning curve. Once mastered,
      however, the Scarf bunionectomy can provide a predictable and satisfying outcome
      for both patient and foot surgeon.

PMID- 11232398
TI  - Distal soft tissue correction for hallux valgus with proximal screw fixation of
      the first metatarsal.
AB  - These early results with short-term to medium-term followup demonstrate the
      effectiveness of this distal soft tissue procedure with proximal realignment in a
      subset of patients with moderate to severe hallux valgus and mobility of the
      first ray. With up to 2-year followup, the correction seems to hold with no
      significant recurrence and only mild increases in the hallux valgus and
      intermetatarsal angles with time. Obviously, longer-term followup with a larger
      group of patients is needed, but these early results are encouraging. In this
      group of patients, this procedure provides reliable correction of hallux valgus
      while possibly avoiding some of the morbidity of the different procedures for
      proximal osteotomy.

PMID- 11232399
TI  - Avascular necrosis of the hallux metatarsal head.
AB  - Avascular necrosis of the first metatarsal head is rare. Although idiopathic
      cases have been reported, AVN of the first metatarsal head is usually iatrogenic
      following surgical correction of hallux valgus using a distal metatarsal
      osteotomy with or without lateral soft tissue release. A thorough understanding
      of the delicate vascular anatomy of the first metatarsal head is essential when
      surgery is considered. Careful operative technique permits a safe combination of
      distal osteotomy and lateral soft tissue release. Because the intraosseous blood
      supply is completely disrupted with distal metatarsal osteotomy, excessive
      capsular release and saw blade penetration into the lateral capsular vessels must
      be avoided. Among the thousands of reported distal metatarsal osteotomies
      performed using a variety of technique modifications of the original procedure
      described by Austin, the prevalence of AVN is low. Undoubtedly, the first
      metatarsal head has an excellent capacity to accommodate to changes in its blood
      supply. Although radiographic changes are frequently observed in the metatarsal
      head following a distal metatarsal osteotomy with or without lateral release,
      rarely do these changes progress to symptomatic AVN. These transient radiographic
      findings probably represent an adjustment period as the metatarsal head recovers
      from vascular compromise. Not only is AVN of the first metatarsal rare, but it is
      rare for it to be symptomatic. Many more cases that are never identified may
      exist. Management of symptomatic AVN of the first metatarsal head has not been
      standardized because of the infrequency of this condition. Anecdotal experience
      suggests that simple activity and shoe modifications may suffice; however, joint
      debridement and metatarsal head decompression may prove beneficial as they have
      in the management of other joints more commonly afflicted with AVN. Finally,
      severe head collapse may be salvaged with MTP joint arthrodesis. In the event
      that a substantial amount of avascular bone must be removed, consideration can be
      given to bone block distraction arthrodesis to avoid transfer metatarsalgia.

PMID- 11232400
TI  - Sesamoid problems.
AB  - The understanding of the pathology and treatment of hallux sesamoid disorders has
      improved considerably over the last few decades. It is interesting to speculate
      what further improvements are on the horizon. Newer imaging methods and possibly
      an increased use of small joint arthroscopy may make it possible to better
      diagnose and treat conditions of these two small bones and to develop better
      biologic and artificial methods of surface replacement. In the meantime
      clinicians should only excise sesamoids if it is really essential.

PMID- 11232401
TI  - The use of osteotomies in the treatment of hallux limitus and hallux rigidus.
AB  - Though osteotomies for relief of hallux limitus and rigidus have been around
      since the earliest surgical corrections, no sound clinical studies have been
      performed to warrant their use over the standard accepted techniques of
      cheilectomy and arthrodesis. These operations are surely more technically
      demanding than such standard procedures, and involve significant increased risk
      and postoperative immobilization than cheilectomy alone. Sound theories such as
      metatarsus primus elevatus and excessive metatarsal length contributing to hallux
      rigidus have never been proven, and no accurate way to diagnose these structural
      deformities has been proposed. These operations are intriguing and some make
      clinical sense. It remains to be seen whether the orthopedic community will adopt
      them based on their merits.

PMID- 11232402
TI  - Hallux rigidus. Excisional arthroplasty.
AB  - The authors feel that capsular interposition arthroplasty can give predictable
      pain relief in carefully selected individuals with severe (grade III) hallux
      rigidus. Attention to the relative lengths of the first and second metatarsals,
      minimal shortening of the proximal phalanx, and use of the dorsal capsule and EHB
      tendon as an interposition all contribute to good to excellent objective and
      subjective results. Approximately 30% of patients undergoing this procedure
      experience some degree of transfer metatarsalgia postoperatively and probably
      require orthoses for sports. The authors feel that this operation presents a
      reasonable alternative to many patients who are candidates for an arthrodesis of
      the first MTP joint for advanced degenerative disease.

PMID- 11232403
TI  - Arthrodesis procedures for salvage of the hallux metatarsophalangeal joint.
AB  - First metatarsophalangeal (MTP) fusion has been recommended as a means to salvage
      various great toe deformities. These deformities include failed hallux valgus
      procedures, failed silicon implants, previous infection, rheumatoid arthritis,
      post-traumatic conditions, hallux rigidus, severe hallux valgus deformities, and
      neuromuscular disorders. A variety of complications, such as hallux varus, first
      MTP joint instability, infection, recurrent hallux valgus, and avascular necrosis
      of the first metatarsal head can develop from hallux valgus deformity treatment
      procedures.

PMID- 11232404
TI  - Periarticular injuries to the hallux metatarsophalangeal joint in athletes.
AB  - The magnitude of hallux MTP injuries can range from a mild sprain to a frank
      dislocation. The importance of coaches, trainers, and physicians recognizing the
      severity of a turf toe injury cannot be overstated. The late sequelae of
      hyperextension injuries can lead to retirement from professional athletics. With
      appropriate conservative treatment, most individuals can return to play, although
      many have some residual pain. Future study in this area should define the
      indications for acute repair versus late treatment following a period of
      conservative modalities. Hyper-plantarflexion injuries also can be debilitating
      injuries, but most respond to rest, taping, anti-inflammatories, ice, and
      strengthening exercises. Lastly, dislocations of the hallux MTP joint can be
      diagnosed and treated after physical examination and appropriate radiographs are
      obtained. All closed dislocations should undergo an attempt at reduction in the
      emergency department after adequate anesthesia is administered. The patient
      should be advised, especially in type I injuries, of the need for possible acute
      operative intervention.

PMID- 11232405
TI  - Arthroscopy of the hallux metatarsophalangeal joint.
AB  - Despite the paucity of literature on the subject of first MTP joint arthroscopy,
      the literature that does exist suggests that it is a worthwhile procedure in
      certain well-selected patients. These patients are usually young to middle-aged
      and have persistent pain and swelling of the first MTP joint that has failed to
      respond to conservative measures. These patients in general are too good for
      arthrodesis or arthroplasty, and certainly in the authors' experience, the
      results have been highly satisfactory.

PMID- 11232406
TI  - Lacerations and ruptures of the flexor or extensor hallucis longus tendons.
AB  - Lacerations and ruptures of the flexor hallucis longus or extensor hallucis
      longus tendon are frequently managed with operative repair. Tendon injuries of
      the hallux are not all alike; careful consideration should be given to the
      mechanism and site of injury, the timing of presentation, and the presence of
      other injuries. Not all tendon injuries of the hallux require repair. The
      effectiveness of a repair will depend on the goals of surgery, which may include
      pain relief, active joint motion, or correction of deformity. When goals are
      clearly defined, a satisfactory result can be expected in most patients.

PMID- 11232407
TI  - [The incidence of the tuberculosis in Romania in I semester , 2000].

PMID- 11232409
TI  - [Respiratory's implications of the gastroesophageal reflux].

PMID- 11232408
TI  - Ventilatory function in pre-school children snorers and nonsnorers.
AB  - BACKGROUND: The value of flow-volume curves alterations for screening for sleep
      apnoea is controversial in adults. OBJECTIVE: The purpose of the present study
      was to assess the possible value of flow-volume curves, in snoring pre-school
      children to detect upper airway abnormal dynamics. METHODS: We analysed
      ventilatory function of 190 children aged 5 to 6 years from nine kindergartens in
      Nancy, France, according to the presence or absence of snoring as declared by
      their parents. RESULTS: More than half (103 = 54%) of the children never snored;
      26 (= 13.7%) snored only with colds, 42 (22.1%) snored occasionally, and 19 (=
      10%) snored habitually. The "saw tooth" sign described in adults by Sanders et al
      in 1981 was absent in all the children in this study, and the height-adjusted
      forced expiratory volume in one second (FEV1/m2) was similar across the four
      groups. The height-adjusted peak expiratory flow (PEF/m2) decreased uniformly
      (but insignificantly) from the group of non-snorer (2.11 +/- 0.381/s/m2) through
      the group of children snoring with colds. (2.05 +/- 0.37) to the group of
      children snoring occasionally (1.99 +/- 0.33); no significant decrease was found
      in the group of habitual snorers (2.06 +/- 0.36). CONCLUSION: In this group of
      young children, we were unable to find the alteration of the expiratory flow
      volume loop described in part of the studies in adults. We cannot, however,
      exclude an alteration of the inspiratory arm of the loop, as this was not
      recorded by us. Our results, suggesting a reduction in peak expiratory flow with
      increase in frequency of snoring need to be validated in a larger population of
      children.

PMID- 11232410
TI  - [Positive pressure continuously or positive pressure continuously autotitratable
      ?].

PMID- 11232411
TI  - [COPD or why COPD is not as asthma ?].

PMID- 11232412
TI  - [Pulmonary tuberculosis and Kaposi syndrome in HIV positive patient].
AB  - The authors point out the case of a young woman with AIDS who presents at the
      same time the test HIV (+), the secondary caseoextensive bilateral pulmonary
      tuberculosis confirmed by the bacterial examination (bK(+) culture), the skin's
      and pulmonary histological manifestations of the Kaposi disease, clinically
      suspected, was confirmed only at the autopsy. Clinical manifestations began with
      skin's modifications, followed 2-3 months later by the diagnosis of a pulmonary
      tuberculosis, the demise decease 4-5 month after the appearance of the first
      skin's lesion.

PMID- 11232413
TI  - [The impact of modern imaging investigation in thoracic surgery].

PMID- 11232414
TI  - [Respiratory pathology induced by medications ( pathogenicity, clinical types,
      diagnosis). Application of the bronchoalveolar lavage].

PMID- 11232415
TI  - [Vocal cords dyskinesia - organic or psychiatric disease ?].

PMID- 11232416
TI  - [Risky diagnosis, rescue intervention].

PMID- 11232418
TI  - [Synchronization of ovulation (OVSYNCH) in high-producing dairy cattle herds. I.
      Fertility parameters, body condition score and plama progesterone contration].
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 injected Gonadotropin Releasing
      Hormone (GnRH) at a random stage of the estrous cycle, followed by an injection
      of a prostaglandin F2 alpha (PGF2 alpha)-analogon seven days later and another
      injection of GnRH two days after PGF2 alpha. Cows were inseminated 24 h after the
      last injection by artificial insemination. Control animals were assigned by
      corresponding lactation number and stage of lactation (month of partus). 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 average milk yield in 1997 and 1998 was 8128.6 +/- 637.0 kg and 8688.3
      +/- 665.0 kg per year, respectively. First service conception rate (FSC) in the
      OVSYNCH group (n = 187) (39.77%) was lower than in the controls (n = 175)
      (54.34%; P < 0.01). In 1997, FSC for the OVSYNCH group did not differ from
      controls (48.94% vs. 55.45%; P > 0.05), whereas in 1998, FSC for the OVSYNCH
      group (29.27%) was significantly lower than in the control group (29.27% vs.
      52.78%) and the OVSYNCH group in 1997 (each time P < 0.01). First service
      conception rate of first lactation cows in the OVSYNCH group was significantly
      lower than in the control group (37.84% vs. 71.05%; P < 0.01), whereas no
      difference was found for the other lactation groups. The mean interval calving to
      first service was shortened in the OVSYNCH group by about 14 d as compared with
      the controls (P < 0.01). However, mean days open only differed by 2.92 d (P >
      0.05). Proportion of cows in each class of lactation number (1., 2. and > 2.
      lactation number) with days open < or = 115 d in the OVSYNCH group were similar
      to controls (P > 0.05). There was a great influence of body condition on the
      success of OVSYNCH. Cows with a body condition score (BCS) of 3.00 had a
      significant better FSC than cows with a BCS < 3.00 (P < 0.05). First service
      conception rate was lower for cows with a BCS > 3.25 and < 2.75 (cows in good and
      poor condition taken together) than for cows with a BCS of 3.00 (P < 0.05). A
      positive effect of OVSYNCH was found in acyclic cows as determined by
      progesterone concentration in blood plasma. Nine out of eleven cows reacted with
      the resumption of ovarian activity. Two cows became pregnant after first
      insemination.

PMID- 11232417
TI  - [Nicotine - drug or medication ?].

PMID- 11232419
TI  - [Occurrence of the fusariotoxins deoxynivalenol and zearalenone in Austrian
      feedstuff in the period from 1995 to 1999].
AB  - 3970 feed samples were analysed for the fusariumtoxins deoxynivalenol and
      zearalenone. 979 (24.6%) of the submitted feed samples from farms with case
      history (swine herds: decreased feed intake and daily weight gain, vomiting,
      cannibalism, impaired fertility, small litter size, weakness of newborn piglets,
      prolonged oestrus of sows; cattle: persistence of follicular ovarian cysts,
      enteritis, decreased slaughter weight, feed refusal). 74% of the samples
      contained cereal and corn ingredients respectively or were complete diet samples
      from swine herds. Based on economic losses the fusariumtoxin deoxynivalenol is
      most important in Austrian husbandry and particularly found in maize, cornsilage,
      wheat and oat.

PMID- 11232420
TI  - [Effect of vaccination on fecal cortisol metabolites in cats and dogs].
AB  - The aim of this study was to apply a cortisol metabolite determination in the
      faeces of cats and dogs for monitoring disturbances. In this experiment faeces
      from every spontaneous defecation of 10 cats and 10 dogs (5 of each sex) were
      collected starting from one day before until two days after the yearly
      vaccination. Concentrations of 11,17-dioxoandrostanes (cat) and cortisol
      equivalents (dog) were determined by enzyme immunoassay (EIA). Faecal cortisol
      metabolites increased and reached peak concentrations (median: 412% in cats and
      417% in dogs, respectively above baseline values) in one of the next two samples
      following the vaccination. This indicated an activation of the adrenocortex, the
      degree to which the different parts (physical and psychological components) of
      the whole vaccination procedure contributed to it was not evaluated. From this
      experiment we conclude that measuring cortisol metabolites in the faeces is a non
      invasive method to monitor stressful conditions in cats and dogs and thus is a
      valuable tool for evaluating animal welfare.

PMID- 11232421
TI  - [Veterinarians teaching at schools of agriculture in Germany (up to 1950)--their
      contribution to animal nutrition].
AB  - During the 19th century in Germany mainly veterinarians working at agricultural
      schools or appointed to veterinary schools from there (for example HAUBNER,
      ROLOFF, DAMMANN, ALBRECHT, KRONACHER) made considerable contributions to the
      development of animal nutrition. They disseminated knowledge of feedstuffs and
      feeding techniques to the interested public at large by books concerning animal
      husbandry and especially "Gesundheitspflege" (health regimen; Tab. 1). Their
      experimental work (Tab. 2) extended from digestibility of feedstuffs, Ca-, P- and
      rumen metabolism (NPN), respectively, to feed intoxications. The interest in
      preventive measures being stronger at school of agriculture than at veterinary
      schools probably stimulated this development.

PMID- 11232422
TI  - [DNA vaccines for veterinary medicine].
AB  - DNA vaccination represents one of the most recent novel approaches to vaccine
      development. Experimentally, DNA vaccines induce a broad range of long lasting
      immune responses including humoral and cell-mediated immunity against infectious
      diseases in humans and animals. Furthermore, DNA vaccines are potentially useful
      for the treatment of autoimmune diseases or cancer. However, most information on
      the efficacy of DNA vaccines has been generated in mice and studies in larger
      animals are limited. In this review, the potential application of DNA vaccines in
      livestock and pet animals are discussed. The principle of this new technology,
      its potency and future perspectives for use in veterinary medicine will be
      outlined.

PMID- 11232424
TI  - [Bronchiolitis in infants. What is the role of oxygen therapy outside the
      hospital?].

PMID- 11232425
TI  - [Bronchiolitis in infants. Are there severity criteria for hospitalization?].

PMID- 11232423
TI  - [ACTH stimulation test for the determination of salivary cortisol and of cortisol
      responses as markers of the training status/fitness of warm-blooded sports
      horses].
AB  - Previous work (Marc et al., 2000) suggested that plasma cortisol responses to
      treadmill exercise or ACTH injection are a reliable marker for performance
      evaluation in warmblood horses. For practical purposes blood sample collections
      and treadmill exercise tests are somewhat troublesome and time consuming. The
      goal of this study was thus to evaluate the use of saliva for cortisol
      determination (by direct EIA) as a marker for performance and to investigate the
      reliability and repeatability of plasma cortisol responses to a single i.v.
      injection of ACTH (50 micrograms or 250 micrograms). Furthermore, the effect of
      training horses for 8 weeks 3 times per week covering the same distance
      (increasing from 3.5 km during the first week to 8 km during the last week)
      either by trotting (approximately 240 m/min) or by cantering (375 m/min) was
      investigated. For this purpose initially ten four-year-old Hannovarian geldings,
      all reared in the same State stud, were used. Mean overall correlation between
      salivary cortisol and plasma cortisol concentrations was 0.64 when samples of
      various points of time were used. However, in spite of attempts to standardize
      saliva sample collection, correlation between salivary cortisol levels and plasma
      cortisol levels at distinct points of time in different tests were low and
      significant (r = 0.85, p < 0.02) only in one test. Thus, salivary cortisol
      measurements for diagnostic purposes are not reliable or useful. The
      repeatability of plasma cortisol responses to ACTH for untrained and trained
      horses were r = 0.86 and r = 0.8 respectively (p < or = 0.01 and p < or = 0.05
      respectively). Training horses either by trotting or cantering did not affect the
      cortisol response either to treadmill exercise or to stimulation by ACTH. It is
      concluded that the relationship between salivary cortisol levels and plasma
      cortisol levels is not close enough to allow the use of salivary cortisol
      determination as marker of the training status/fitness of horses. The
      repeatability of the cortisol response to ACTH is similar to the cortisol
      response to treadmill exercise. Based on plasma cortisol responses to ACTH or
      treadmill exercise training horses by cantering at low speed is not superior to
      training by trotting for the fitness of horses.

PMID- 11232426
TI  - [Bronchiolitis in infants. Actual organization of care].

PMID- 11232427
TI  - [Role of non-invasive oxygen saturation pulse oximetry in the evaluation and
      surveillance of bronchiolitis].

PMID- 11232428
TI  - [Bronchiolitis in infants. What are the techniques of bronchial and upper airway
      respiratory therapy adapted to infants?].

PMID- 11232429
TI  - [Management of bronchiolitis in the infant. Recommendations. Long text].

PMID- 11232430
TI  - [Is bronchial and/or upper airway chest physical therapy indicated in
      bronchiolitis in infants? Stating the prescription modalities].

PMID- 11232431
TI  - [Role of respiratory therapy in the treatment acute bronchiolitis in infants].

PMID- 11232432
TI  - [Bronchiolitis in infants. Corticoids].

PMID- 11232434
TI  - [Role of bronchodilators in the treatment of acute infant bronchiolitis].

PMID- 11232433
TI  - [Infant bronchiolitis: prevention of transmission and long-term respiratory
      morbidity].

PMID- 11232435
TI  - [Criteria for hospitalization, for severity and for the role of oxymetry in
      infant bronchiolitis].

PMID- 11232436
TI  - [Organization of care during bronchiolitis epidemics].

PMID- 11232437
TI  - [Therapeutic aspects of infant bronchiolitis, other than corticotherapy and
      bronchodilators].

PMID- 11232439
TI  - [Acute bronchiolitis in the infant. Definition].

PMID- 11232438
TI  - [Bronchiolitis in infants. Natural history of the disease].

PMID- 11232440
TI  - [Acute bronchiolitis. Natural history].

PMID- 11232441
TI  - [Bronchiolitis in infants. Clinical criteria of severity for hospital admission].

PMID- 11232442
TI  - [Management of bronchiolitis in the infant. Short text].

PMID- 11232443
TI  - [Use of corticoids in acute bronchiolitis in infants].

PMID- 11232444
TI  - [Prevention of short and long term recurrences after a first episode of
      bronchiolitis].

PMID- 11232445
TI  - [Complications of bronchiolitis].

PMID- 11232446
TI  - [Prevention of bronchiolitis. Measures to take in families? In the office? In
      hospital services? Safety modes to propose to children].

PMID- 11232447
TI  - [Bronchiolitis in infants. Virology].

PMID- 11232448
TI  - [Bronchodilator treatments during acute bronchiolitis in infants].

PMID- 11232449
TI  - [Epidemiology of infant bronchiolitis in France].
AB  - Respiratory syncytial virus (RSV) bronchiolitis has become a major public health
      concern in France during the last decade. This winter epidemic mobilizes each
      year considerable means through the private ambulatory and public hospital nets.
      The epidemiology of RSV bronchiolitis remains difficult to characterize because
      of the lack of consensus for its definition. Several French studies are described
      here which suggest an increase in severity of the epidemics since 10 years in
      France. Peaks are more important each year and involve younger patients. This
      phenomenon does not concern other winter epidemics such as rotavirus
      gastroenteritis or influenza in infants. A policy of prevention of RSV
      bronchiolitis seams to be necessary in our country in the future.

PMID- 11232450
TI  - [Bronchiolitis in infants. What are the general care measures?].

PMID- 11232451
TI  - [Bronchiolitis in infants. Antibiotics and antivirals].

PMID- 11232453
TI  - [Adoption today].

PMID- 11232452
TI  - [Bronchiolitis in infants. Mucolytics, antitussives and other drugs].

PMID- 11232454
TI  - [Analgesia with oxygen-nitrous oxide mixture during percutaneous renal biopsy in
      children].
AB  - The efficacy of an inhaled equimolar mixture of nitrous oxide and oxygen
      (Entonox/MEOPA) to prevent procedural pain during renal percutaneous biopsies in
      children was assessed. PATIENTS AND METHODS: One hundred and seven children who
      underwent 113 renal biopsies during a 17-month period were included in a
      prospective uncontrolled pediatric study. Efficacy was evaluated using patients'
      answers to a questionnaire and nurses' observations. RESULTS: Pain was absent in
      86.5% of the cases. Mild adverse events were noted in one-third of the
      procedures, and were always reversible within a few minutes when the inhalation
      stopped. Acceptability was good. The use of this gas is easy and safe provided a
      few precautions are observed. CONCLUSION: Inhaled equimolar mixture of nitrous
      oxide and oxygen prevents procedural pain during renal percutaneous biopsies.

PMID- 11232455
TI  - [CFTR gene analyis in 207 patients with cystic fibrosis in southwest France: high
      frequency of N1303K and 1811+1.6bA>G mutations].
AB  - The large molecular heterogeneity in cystic fibrosis (CF) represents the main
      difficulty for the genotype characterization. Moreover, numerous studies have
      reported considerable variations in frequencies of cystic fibrosis transmembrane
      conductance regulator (CFTR) mutations in different populations. MATERIAL AND
      METHODS: We analyzed the genotype of 207 CF children living in southwest France.
      RESULTS: Among 50 identified mutations, we report for some of them a widely
      modified incidence compared with those observed in other regions of France. These
      differences were more significant in the subset of the CF chromosomes originating
      in southwest France. Thus, the 1811 + 1.6 kbA > G mutation, rarely observed in
      the other French regions (< 0.5%), proved to be, with a frequency of 8.8%, the
      most frequent mutation after the F508 deletion (57%). The frequencies of N1303K,
      1811 + 1.6 kbA > G and R334W mutations were also clearly increased: 7.9 and 2.6%,
      respectively. CONCLUSION: We show that the southwest of France is characterized
      by a specific mutational spectrum. We consider that these regional data on the
      spectrum of CF mutations are crucial to develop more accurate and less expensive
      molecular screening strategies for cystic fibrosis in France.

PMID- 11232456
TI  - [Prolonged length of stays in pediatric intensive care. Retrospective study of
      100 stays].
AB  - New issues have arisen in pediatric intensive care units, especially concerning
      long-stay patients. The aims of the present study were to describe the etiologic
      factors of these long-stay patients and to recognize the comorbidities. MATERIAL
      AND METHODS: Ninety-five patients who had a total of 100 hospitalizations of more
      than 30 days were admitted to the pediatric intensive care unit at Robert-Debre
      Hospital during a 3-year period (1993-1995); this accounted for 9.1% of total
      admissions. We retrospectively reviewed these 100 long-stay hospitalizations.
      RESULTS: Most of these patients were newborns (65%). Patients with severe
      congenital anomalies (44 patients) and very premature infants (26 patients)
      constituted the majority of long-stay patients. The mean duration of mechanical
      ventilation for the 95 patients was 110 days (ranges 17-789 days). Two factors of
      comorbidity were found: gastroesophageal reflux (41% of cases) and nosocomial
      infections (89% of cases). CONCLUSION: In order to prevent long stays, pediatric
      intensive care units must be directed toward these factors.

PMID- 11232457
TI  - [Value of thoracoscopy in purulent pleuresies in children younger than four
      years].
AB  - Video-assisted thoracoscopic surgery is widely performed in adults but there are
      few publications concerning the paediatric population. The objective is to effect
      optimal adhesiolysis of post-pneumonic loculated empyema with lower morbidity.
      PATIENTS AND METHODS: Over a 4-year period we used thoracoscopic debridement in
      five children younger than 4 years of age with loculated thoracic empyema. All
      patients failed initial treatment, including antibiotics and chest tube drainage.
      Early sonographic evaluation of the empyema organization guided the most
      appropriate moment for the intervention. The average duration of tube drainage
      after thoracoscopy was 4 days (range: 1 to 7 days). RESULTS: All patients made an
      uneventful postoperative recovery. At a follow-up visit 1 month after discharge,
      the children were clinically asymptomatic; however, some degree of pleural
      thickening was still visible on chest X-rays. CONCLUSION: In skilled hands,
      thoracoscopy is a safe procedure for post-pneumonic empyema in young children,
      providing a rapid clinical and radiological recovery with a good cosmetic result.

PMID- 11232458
TI  - [Osteogenesis imperfecta: a new, early therapeutic approach with biphosphonates.
      A case report].
AB  - Management of type III osteogenesis imperfecta (O.I.) (brittle bone disease) is
      primarily supportive; early introduction of cyclic intravenous pamidronate
      administration in children younger than 2 years of age is an innovative and
      promising therapeutic approach. CASE REPORT: We present the case of a 6-month-old
      infant, whose preliminary data have already been partly published, with severe
      type III O.I. referred because of aching and crumbling from multiple fractures.
      Cyclic intravenous disodic pamidronate administration improved the clinical
      status (fracture incidence, pain, growth curve) and biological status (bone
      density, osseous alkaline phosphatases, urinary desoxypiridoline excretion),
      allowing a remarkable recovery. CONCLUSION: Biphosphonates are a new and
      innovative therapeutic agent in O.I. Clinical safety, easy administration, and
      overall efficacy are likely to extend their use in severe type III O.I. from the
      very first months of life, the time of best efficacy.

PMID- 11232459
TI  - [X-linked recessive chondrodysplasia punctata. Cytogenetic study and role of
      molecular biology].
AB  - Among the many acquired or constitutional causes of chondrodysplasia punctata,
      the X-linked recessive form is well individualized. CASE REPORT: A male newborn
      presented a dysmorphic syndrome with a marked nasal hypoplasia, a macroglossia
      and a short neck. The diagnosis of chondrodysplasia punctata was made by
      radiography whereas the chromosomal chart revealed the existence of an additional
      Y fragment in Xpter, effectuating a partial disomy Yp and a monosomy Xpter.
      Molecular biology showed a deletion of very small size, isolated and located
      between the gene missing aryl sulfatase E and the microsatellite DXS 1233, sping
      gene MRX2 (non-specific gene of mental retardation), and making it possible to
      give the reassuring elements as regards the psychomotor prognosis, sometimes
      compromised in this disorder. CONCLUSION: In case of chondrodysplasia punctata
      with dysmorphy, it is important to execute a chromosomal chart in the search for
      a chromosomal reorganization on the X and a study in molecular biology.

PMID- 11232460
TI  - [Endoscopic diagnosis of a gastric heterotopic pancreas and esophageal atresia:
      an incidental association?].
AB  - Heterotopic or aberrant pancreas is a rare congenital anomaly, usually
      asymptomatic. The preoperative diagnosis is difficult but most cases of gastric
      ectopic pancreas have a unique appearance that often makes possible a diagnosis
      in the absence of histologic confirmation. A well-delineated submucosal, firm
      mass with central umbilication is characteristic of gastric ectopic pancreas. To
      the best of our knowledge, the association of esophageal atresia and gastric
      heterotopic pancreas has never been reported previously. CASE REPORTS: We report
      two cases of heterotropic pancreas associated with esophageal atresia. Both
      diagnoses were incidental findings and concerned children operated on at birth
      for esophageal atresia. Although a definitive diagnosis is histologic, the
      endoscopic appearance made it possible to maintain this diagnosis. CONCLUSION:
      Some symptoms have been attributed to ectopic pancreas, and malignant
      degeneration has been reported in adults. Management continues to be debated:
      some authors recommend surgical resection while others, as we do, prefer initial
      therapeutic abstention.

PMID- 11232461
TI  - [Cerebellar vermis hypoplasia with extracerebral involvement (retina, kidney,
      liver): difficult to classify syndromes].
AB  - Congenital cerebellar vermis hypoplasias diversely associated with retinopathy,
      nephropathy and hepatopathy are rare syndromes of uncertain nosology. We report
      three new cases. CASE REPORTS: Case 1. A 3-month-old boy presented a brief
      nystagmus. At the age of 2 years, he had facial dysmorphia, hypotonia, ataxia,
      ocular motor apraxia and neurodevelopmental impairment with cerebellar vermis
      hypoplasia. The electroretinogram showed asymptomatic retinal involvement. At the
      age of 6 years, he developed chronic renal failure. The diagnosis of familial
      juvenile nephronophthisis was made by detection of a large homozygous deletion of
      the NPH1 region. Case 2. A term newborn boy presented apnea, tachypnea,
      hypotonia, nystagmus, ptosis, lack of visual contact and hepatomegaly. He had
      facial dysmorphia, bilateral optic coloboma with chorioretinal dysplasia and
      cerebellar vermis hypoplasia. There were cysts in the kidneys with increased
      echogenicity and lack of demarcation between the pyramids and the cortex. The
      liver was hyperechoic with fibrosis. At the age of 15 months, the child had
      severe developmental delay. He had bouts of fever. A search for a large
      homozygous deletion of the NPH1 region was negative. Case 3. A term newborn girl
      presented difficulty to suck, cyanosis, hypotonia and ptosis. Later, the child
      had a developmental delay. At the age of 6 years, she developed chronic renal
      failure (nephronophthisis). At the age of 23 years, she presented divergent
      strabismus, ataxia, mental retardation, slow ocular pursuit and facial
      dysmorphia. The neuroimaging showed a cerebellar vermis hypoplasia. A search for
      a large homozygous deletion of the NPH1 region was negative. CONCLUSION: The
      diagnosis of cerebellar vermis hypoplasia requires searching for retina, kidney
      and liver involvement. The large homozygous deletion of the NPH1 region has to be
      investigated if typical familial juvenile nephronophthisis is associated. Because
      cerebellar vermis hypoplasia with extracerebral involvements (retina, kidney,
      liver) is part of many different closely related syndromes, a clear molecular
      classification is necessary for accurate genetic counselling and an early
      prenatal diagnosis.

PMID- 11232462
TI  - [Mental disorders in children: the value of epidemiology].
AB  - Epidemiological research on the mental health of children is not well developed
      in France, as demonstrated by the very small number of publications on the
      subject, especially in French. The purpose of this article is to show the
      contribution of epidemiology to an understanding of childhood mental illness. We
      emphasize descriptive epidemiology (currently the most developed component), but
      discuss analytic and evaluative epidemiology as well. We have thus considered
      methodological issues related to the advantages and limitations of techniques
      employed, using concrete examples from international publications. For example,
      an extensive review of the literature reveals considerable disparity in figures
      on the prevalence of psychiatric disorders, chiefly because of problems of
      variation in definitions used and in the places and techniques of data collection
      (especially screening tools and diagnostic classifications). Only studies carried
      out in representative samples of the general population allow reliable evaluation
      of frequency, but these are particularly difficult and costly. The same may be
      said for follow-up studies, in particular those on birth cohorts, whose principle
      importance is that they enable the identification of predictive factors for
      mental disorders, starting from earliest childhood. Entire areas are currently in
      need of development, such as the genetic epidemiology in mental illness, clinical
      trials, or the evaluation of programs. Epidemiology enables the evaluation of
      service needs, the identification of 'risk groups' and a scientific approach to
      explanatory factors. In a country such as France where nearly all children are in
      the school system from the age of 3 years on, schools should become a place for
      early detection, which assumes a considerable increase in the means available and
      an innovative policy in the training of health personnel, especially in the area
      of mental health.

PMID- 11232463
TI  - [The child with recurrent infections: which screening for immunoe deficiency?].
AB  - A child with recurrent infections represents a challenge to the pediatrician who
      must identify, among a large number of repeatedly infected but nevertheless
      healthy children whose parents need to be reassured, the rare cases of
      potentially severe immune deficiency. This can be most successfully achieved
      through the measurement of IgA, IgG, and antibody titers to vaccine (tetanus,
      diphtheria, Haemophilus influenzae B) and exposure (pneumococcus) antigens. The
      presence of normal antibody responses makes it possible to rule out underlying
      immune deficiency in a sensitive and specific manner. Conversely, abnormally weak
      antibody responses identify the children who have to be referred without delay
      for further investigation of a potential immune defect. This article indicates
      for which pediatric patients an immunodeficiency screening should be considered,
      and how to analyze its results.

PMID- 11232464
TI  - [Meconium in the amniotic fluid: prevention of meconium aspiration and elective
      tracheal suction].
AB  - For many years early systematic intubation and tracheal suction have been
      advocated for meconium-stained infants. Recent data show that they do not reduce
      the frequency of pulmonary meconium aspiration and underline the importance of a
      preventive attitude (i.e., intrapartum oropharyngeal suction before shoulder
      clearing and thoracic compression before first breathing) together with a
      selective tracheal suction only in the newborns with obvious oropharyngeal
      meconial staining.

PMID- 11232465
TI  - [Neonatal nasal obstruction].
AB  - Because neonates are obligate nose breathers, neonatal nasal obstruction may have
      serious consequences. Prompt diagnosis and appropriate treatment are essential to
      avoid severe hypoxia. The most common cause of neonatal nasal obstruction is
      rhinitis. However, it is essential to first rule out anatomical causes such as
      choanal atresia and stenosis, pyriform aperture stenosis, traumatic deformation
      or tumors, as these conditions may be life-threatening and require prompt
      surgical treatment.

PMID- 11232466
TI  - [A case of tuberculous meningitis in a vaccinated child].

PMID- 11232467
TI  - Biomechanics of the ankle joint. A perspective on total ankle replacement.
AB  - The biomechanics of the ankle present a unique set of challenges for arthroplasty
      surgery. Its biomechanics are not simple. Although the ankle joint may seem like
      a hinge, it is not in a line perpendicular to the tibia. The axis of rotation
      does not stay constant during range of motion, despite a relative congruency of
      this joint. Allowing for rotational forces must be accomplished, while
      maintaining the stability of the joint and its components. Success of the
      arthroplasty depends on how successful designs can dissipate these rotational
      forces, while maintaining the stability of the joint. It is not yet clear from
      the biomechanical analysis of the normal ankle joint that this dissipation of
      forces has been accomplished successfully in modern implants, although early
      results in the semiconstrained designs are encouraging. Careful assessment of
      long-term follow-up will determine how close the present designs are to mimicking
      the unique requirements of the arthritic foot and ankle. Further work on the
      biomechanics of these replacements would be beneficial.

PMID- 11232468
TI  - Perspective on total ankle replacement.
AB  - Total ankle arthroplasty has become a viable alternative to ankle arthrodesis.
      Modern implant designs involve a syndesmosis fusion and resurfacing of the medial
      and lateral recesses of the ankle joint or the use of a three-component, mobile
      bearing implant. In limited clinical series, the early results of both these
      prosthetic design approaches are encouraging. In selected patients, ankle
      arthroplasty is an effective approach to relieving pain and improving function.
      Selected patients can be offered a total ankle replacement as an alternative
      option to arthrodesis in the treatment of end-stage ankle arthritis. Further
      development of prosthetic designs, which minimize bone resection and restore
      normal ankle motion, is needed.

PMID- 11232469
TI  - Extended hindfoot fusions and pantalar fusions. History, biomechanics, and
      clinical results.
AB  - Contemporary techniques of hindfoot and ankle arthrodesis can result in a high
      rate of osseous union, pain relief, and patient satisfaction. Methods range from
      open approaches to fully arthroscopic surgical techniques. Arthrodesis should be
      limited to the joints involved with the arthritic, deforming, or neuromuscular
      process because the rate and severity of progressive adjacent joint degeneration
      appear related to the number of joints fused initially. Appropriate joint
      position, maintained with stable internal fixation applied in compression and
      augmented with bone-graft material when necessary, should be considered the gold
      standard for most hindfoot and ankle arthrodeses. External fixation may be used
      in the revision or salvage setting if needed or when soft tissues or bone stock
      do not permit stable internal fixation. Meticulous attention must be given to the
      handling of soft and hard tissues as well as to correction of the underlying
      deformity and to appropriate positioning of the joints in question. Newer
      techniques, such as intramedullary fixation, arthroscopic or arthroscopically
      assisted ankle arthrodesis, and total ankle arthroplasty, have shown some promise
      and warrant more extensive study.

PMID- 11232470
TI  - Ankle chondral injuries and repair.
AB  - The success of cartilage repair in the ankle and other joints rests on multiple
      factors. Because native cartilage healing fails to produce hyaline, organized
      cartilage, the challenge lies in activating an appropriate healing response. The
      combination of an optimal structural matrix, infusion of pleuripotent cells, and
      gene-modified tissue engineering to activate an appropriate healing response
      appears most sensible. Until such technology is available for use in humans,
      however, autologous chondrocyte transplantation and osteochondral transfer
      procedures are attractive alternatives.

PMID- 11232471
TI  - Controversies in ankle fracture treatment. Indications for fixation of stable
      Weber type B fractures and indications for syndesmosis stabilization.
AB  - Although the treatment of ankle fractures is often straightforward, several
      controversies remain. This article reviews the need for open reduction and
      internal fixation of the displaced supination-external rotation fracture, and
      contrasts the studies that mandate anatomic reduction with clinical results. The
      many issues surrounding syndesmosis fixation are also reviewed, including the
      need for fixation of distal fractures and the timing of screw fixation.

PMID- 11232472
TI  - Hybrid external fixation of tibial pilon fractures.
AB  - Although external fixation reduces drastically the number of iatrogenic
      complications compared with acute open reduction and plate fixation, the
      prognosis for functional recovery after a pilon fracture remains guarded. Many
      authors have applied validated patient outcome measures to patients who have had
      pilon fractures. These studies confirmed that there are significant decreases in
      general health perceptions, physical and emotional role function, pain, and
      energy levels in patients who have suffered pilon fractures, regardless of the
      treatment modality. The high-energy tibial pilon fracture with soft tissue
      compromise remains a treatment dilemma. Hybrid external fixation with limited
      open reduction has proved to be a safe, reproducible, and effective treatment
      modality for this complex fracture.

PMID- 11232474
TI  - Complex ankle instability.
AB  - Complex ankle instability can be linked to a variety of causes. It is essential
      to evaluate these patients adequately, including a clinical history, evaluation
      of prior records and diagnostic studies (if available), and current radiographic
      studies. With appropriate evaluation and assessment, the underlying cause can
      [figure: see text] be determined and a reasonable surgical plan developed. With
      appropriate planning, adequate improvement usually can be expected.

PMID- 11232473
TI  - Open reduction and internal fixation of tibial pilon fractures.
AB  - Although it is evident that the fracture of the tibial plafond is a complex,
      often debilitating injury, its management is not clear. These injuries generally
      fall into one of two categories. The low-energy, rotational type of fracture has
      been shown to have excellent clinical and functional results with open reduction
      and internal fixation. The high-energy, compression type of fracture has had
      uniformly moderate results and historically high complication rates. Some authors
      think that bridging external fixation with or without limited internal fixation
      should be employed in high-energy fractures. Others believe that open reduction
      and internal fixation to avoid articular incongruence and development of axial
      malalignment is needed for good long-term outcome. The authors believe the
      latter. Staging the treatment of the patient can minimize development of soft
      tissue complications. The authors follow the recommendations of Patterson and
      Sirkin and believe that high-energy pilon fractures should be temporized with an
      external fixator with or without fibular plating to restore length. Any open
      would should be addressed at this time. Definitive fixation should be planned for
      between 10 and 14 days, by which time the soft tissue envelop is likely to be
      ready to accept the further insult of surgery. The surgical technique should be
      well planned for and include the use of meticulous soft tissue techniques and
      indirect reduction methods. With the proper attention to detail, long-term
      results will be maximized.

PMID- 11232475
TI  - Charcot's foot.
AB  - Charcot's foot used to be considered an unusual complication of diabetic
      peripheral neuropathy. With the current appreciation that approximately 25% of
      adult diabetics have an appreciable peripheral neuropathy, it is understandable
      that Charcot's neuro-osteoarthropathy has become recognized as a major problem
      for clinicians caring for diabetics. Differentiation from acute diabetic foot
      infection is the first challenge. Once Charcot's foot is identified, treatment
      generally involves immobilization during the acute inflammatory stage. When
      deformity develops, the orthopedic foot and ankle surgeon must decide whether
      accommodative care with a combination of inlay depth shoes, accommodative foot
      orthoses, and ankle-foot orthoses is adequate. If a plantigrade weight-bearing
      surface cannot be achieved, surgical stabilization or reconstruction requires
      rigid stabilization in a poor biomechanical environment using tools that are not
      designed for structures as small as the foot. The controversies presented to
      clinicians charged with care of this difficult patient population are as follows:
      1. When to allow weight bearing in the acute phase of the disease process. 2.
      Whether prefabricated devices are as successful as the total contact cast in the
      acute phase. 3. Early surgical stabilization versus accommodation when deformity
      first develops. 4. Late reconstruction versus accommodation or amputation in the
      deformed late stages.

PMID- 11232476
TI  - Sepsis and osteomyelitis about the ankle joint.
AB  - Sepsis and osteomyelitis about the ankle joint present a challenging clinical
      problem. Osteomyelitis usually follows open fracture of the distal tibia, often
      with a pilon fracture component. This article outlines the prevention of
      osteomyelitis in these difficult fractures. Treatment of subsequent osteomyelitis
      and sepsis, including the authors' experiences, is discussed. Septic ankle
      arthritis can occur hematogenously. In some patients, the optimal treatment for
      concomitant osteomyelitis and sepsis is a below knee amputation.

PMID- 11232478
TI  - High-tech help for hearing loss.

PMID- 11232477
TI  - Diabetes and heart health.

PMID- 11232479
TI  - The latest strategies for treating prostate cancer.

PMID- 11232480
TI  - An action plan for relieving joint pain.

PMID- 11232481
TI  - Are there any drawbacks to smoothing out lines and wrinkles with Botox
      injections?

PMID- 11232482
TI  - How often should I have a bowel movement?

PMID- 11232484
TI  - Are there indications for intravenous acid-inhibition in the prevention and
      treatment of upper GI bleeding?
AB  - Administration of acid-inhibiting drugs in the prevention of stress ulcer
      bleeding is based on the hypothesis that pepsin activity is pH-dependent. In the
      treatment of peptic ulcer bleeding, acid-inhibition is based on the hypothesis
      that clot formation and clot lysis depend on intraluminal pH. Medications used in
      the prophylaxis of stress ulcer bleeding comprise antacids, sucralfate, H2
      receptor antagonists and proton pump inhibitors (PPIs). Two studies show that
      prophylaxis with ranitidine is more effective than prophylaxis with sucralfate.
      PPIs give a more predictable and sustained pH control during prolonged dosing
      than ranitidine. Two trials show that patients who receive omeprazole run a
      significantly lower risk of bleeding than patients receiving ranitidine. The
      optimal initial treatment for bleeding peptic ulcers in patients with active
      bleeding or non-bleeding visible vessel is endoscopic therapy. Among patients
      with non-bleeding visible vessels or adherent clots who do not undergo endoscopic
      therapy, acid-inhibition with PPIs may significantly reduce rebleeding rate and
      need for surgery. After endoscopic therapy acid-inhibition with PPIs may have a
      beneficial effect on hemostasis. One direct comparative trial showed no
      significant difference in clinical outcomes between patients whether treated with
      high-dose or low-dose PPI. The use of multiple medications to treat concurrent
      conditions in ICU patients or bleeding peptic ulcer patients increases the risks
      of clinically important metabolic drug interactions. More recently developed PPIs
      are less dependent on CYP2C19 and probably have a lower potential for metabolic
      drug interactions. For both indications the optimal dose PPI has to be
      established.

PMID- 11232485
TI  - Chemoprevention of colorectal cancer by non-steroidal anti-inflammatory drugs.
AB  - AIM: To critically analyse the role of NSAIDs in colorectal cancer. METHODS:
      Update of the chemoprotective effect of NSAIDs on colorectal cancer. RESULTS AND
      CONCLUSION: Over the past 20 years exciting developments in clinical and basic
      research have opened up the possibility of NSAID-induced colorectal cancer
      chemoprevention. In particular, disclosure of the multistep genetic pathway of
      colorectal carcinogenesis and recognition of the impact of the COX-2 gene on this
      process have been of utmost importance. These findings have led to the
      possibility of colorectal cancer prevention by the administration of agents such
      as NSAIDs. Although it is accepted that these agents are potent inhibitors of
      colorectal carcinogenesis, their side effects in long-term use are of concern to
      clinicians dealing with colorectal cancer prevention. Moreover, neither the dose
      nor the duration of the medication, nor the most ideal compound with respect to
      protective effects against colorectal cancer, has been defined. Recently,
      selective COX-2 inhibitors have been developed which may show additional benefit
      compared to the classical NSAIDs. However, their efficacy and safety profiles
      need to be established firmly before large-scale use in colorectal cancer
      prevention can be considered. Based on the exciting developments it is
      anticipated that a more precise understanding of the molecular details of
      colorectal carcinogenesis will finally lead to the optimal chemopreventive
      regimen.

PMID- 11232486
TI  - Pharmacoepidemiology and gastroenterology: a close couple.
AB  - The discipline of pharmacoepidemiology has always been strongly linked with the
      problem of gastrointestinal injury caused by non-steroidal anti-inflammatory
      drugs, and has led to a close liaison between gastroenterology and
      pharmacoepidemiology. AIM: This paper discusses three important areas of
      pharmacoepidemiological interest relevant to gastroenterologists: confounding by
      indication and channeling bias, drug exposure patterns, and postmarketing
      surveillance studies. (i) Drug prescribing is associated with a patient's
      prognosis and disease status, called indication for treatment. These patient
      disease characteristics can drive drug channeling in risk populations and create
      confounded drug-effect associations. (ii) Drug exposure is the result of the
      'natural' experiment of pharmacotherapy over time. Reliable information on the
      time-sequence of events in relation to drug exposure is required to evaluate both
      beneficial and adverse effects of drug therapy. (iii) Postmarketing surveillance
      studies provide intensive learning about drug effects when large spectra of
      patients with various medical backgrounds, prognoses, co-morbidity, and the like,
      are exposed to the drug. Information on drug use and patient outcomes in 'real
      life' populations is necessary to bridge normal practice experiments with
      randomized clinical trials.

PMID- 11232487
TI  - Effects of Helicobacter pylori infection on endocrine and exocrine mucosal
      functions in the upper gastrointestinal tract.
AB  - BACKGROUND: Helicobacter pylori infection affects the concentration of regulatory
      peptides such as gastrin, somatostatin and cholecystokinin and the concentration
      and activity of glutathione and glutathione S-transferases in the gastric mucosa.
      METHODS: Literature review. RESULTS: Although some of these peptides have been
      known since the beginning of this century, their action has changed since the
      discovery of H. pylori infection in 1983. Chronic infection with H. pylori might
      lead to an increased risk in developing gastric cancer. Glutathione S
      transferases are involved in the cellular detoxification of xenobiotics and other
      toxic compounds. Since there is a close inverse relationship between the activity
      of glutathione S-transferase and incidence of malignancies in the
      gastrointestinal tract, the possible relation between H. pylori infection and
      activity of glutathione S-transferases in the gastric mucosa is discussed.
      CONCLUSION: The effect of H. pylori infection on regulatory peptides and
      glutathione/glutathione S-transferases might play a role in the development of
      neoplastic changes of the H. pylori-infected gastric mucosa.

PMID- 11232488
TI  - Refractory coeliac disease: a window between coeliac disease and enteropathy
      associated T cell lymphoma.
AB  - The treatment of coeliac disease (CD) is straightforward and simple: life-long
      adherence to a gluten-free diet. However, in a small subgroup of patients, the
      clinical and histological abnormalities persist or recur. This non-responsiveness
      leaves a poorly understood syndrome known as refractory coeliac disease (RCD). A
      specific definition of RCD is lacking in the literature. We speculate that RCD
      may appear in a subgroup of coeliacs with persisting histologic abnormalities. In
      all patients screened for RCD we look for DQ2 and DQ8. In non-DQ2/DQ8 patients we
      reconsider the diagnosis of CD and of auto-immune enteropathy. Most of the
      patients referred to us because of suspicion of RCD are affected by other
      diseases. Probably the commonest cause of non-responsiveness is continued gluten
      intake. Exocrine pancreas insufficiency, hyperthyroid disease, collagenous
      colitis are other common explanations. RCD and enteropathy-associated T cell
      lymphomas (EATL) can be distinguished by intra-epithelial lymphocyte phenotyping
      and TCR-gamma gene rearrangements. In RCD, an unexplained sustained stimulation
      of T cell cytotoxic activity is present. Immunosuppressive treatment might
      moderate this. Cyclosporine has been reported as a resounding success in case
      reports; however, our results were disappointing. We suggest azathioprine and
      steroids in RCD without aberrant T-lymphocytes in their mucosa. However, in RCD
      with aberrant T-lymphocytes we suggest chemotherapy. As the prognosis of EATLs is
      extremely poor the early detection of RCD with aberrant T cells is crucial.

PMID- 11232489
TI  - New developments in the treatment of irritable bowel syndrome.
AB  - The irritable bowel syndrome (IBS) is one of the most common gastrointestinal
      conditions encountered by general practitioners, and it accounts for a great deal
      of the workload of gastroenterologists in secondary care. Research to date
      indicates that several factors contribute to the development of IBS, of which
      disturbed gastrointestinal motility, altered visceral perception and psychosocial
      factors are regarded as the three most important mechanisms interacting in the
      development of this disorder. Most pharmacological research has been based on
      these insights. Several agents capable of modulating either motility or
      sensitivity are currently under investigation. Potential drugs in the treatment
      of diarrhoea-predominant IBS are the more selective antispasmodics, such as the
      M3-receptor antagonists (e.g. zamifenacin, darifenacin). In constipation
      predominant IBS the colokinetic effects of the selective 5HT4 agonists
      prucalopride and tegaserod are of great interest. Since altered visceral
      perception is thought to play an important role in the genesis of abdominal pain
      and bloating in many patients with IBS, new drugs are targeted at modulating the
      sensitivity, such as 5HT3 antagonists (e.g. alosetron), kappa-agonists (e.g.
      fedotozine) and somatostatin analogues. Furthermore, psychosocial factors should
      not be overlooked, since these appear to be of great influence on the clinical
      outcome of IBS.

PMID- 11232490
TI  - Topics in Helicobacter pylori infection: focus on a 'search-and-treat' strategy
      for ulcer disease.
AB  - Several new and interesting issues regarding Helicobacter infection are
      discussed. Test-and-treat strategies in young dyspeptics will do little to reduce
      the burden of ulcer disease. The prevalence of Helicobacter infection in young
      people is low and still declining; the incidence of ulcer disease is therefore
      low. Ulcer disease has a high prevalence and most cases occur in older people.
      There is a large pool of people who have suffered from a documented peptic ulcer
      in the past and most are still intermittently symptomatic. If we are to decrease
      the prevalence of ulcer disease we ought to promote case finding. Only 'search
      and-treat' strategies will help to eliminate ulcer disease. These can focus on
      patients with an ulcer history or on populations that regularly use acid
      suppressants. Such strategies, of which several examples are discussed, are cost
      effective and lead to improved health in the target population. We also discuss
      the use of serology as a follow-up instrument after anti-Helicobacter therapy and
      discuss issues regarding Helicobacter therapy in relation to antimicrobial
      resistance in The Netherlands.

PMID- 11232491
TI  - Osteopenia and osteoporosis in Crohn's disease: prevalence in a Dutch population
      based cohort.
AB  - Reduced bone mineral density (BMD) has been reported in 3-77% of patients with
      inflammatory bowel disease (IBD). The majority of these studies are cross
      sectional and from tertiary referral centres. The aim of our study was to
      estimate the prevalence of metabolic bone disease and of symptomatic fractures in
      a population of patients with Crohn's disease (CD) living in a well-defined
      geographic area. Patients with CD living in three adjacent municipalities within
      the IBD South-Limburg study area were investigated. BMD was measured by dual X
      ray absorptiometry (DXA) of the femoral neck, lumbar spine and total body. The
      population comprised of 181 CD patients, 23 of whom were excluded. One-hundred
      and-nineteen (75%) of the 158 eligible patients (37 males, 82 females with a mean
      age of 42 years (17-78)) were investigated. Osteopenia of lumbar spine and/or
      femoral neck was found in 45% of patients. Osteoporosis was found in another 13%
      of patients. Mean BMD (T-score) of femoral neck was significantly lower than of
      lumbar spine (P < 0.001). Male CD patients and patients aged under 18 at
      diagnosis are more at risk of having a low bone mass at the lumbar spine (P <
      0.001) and total body (P = 0.018). The prevalence of osteoporosis in
      postmenopausal CD patients (29%) was significantly higher than in premenopausal
      patients (3%) (odds ratio: 12). Twenty-nine of 119 (24%) patients had a history
      of symptomatic fractures. Osteopenia and osteoporosis are frequent in CD and
      should have the full attention of the treating physician.

PMID- 11232492
TI  - Sexual and bladder dysfunction after total mesorectal excision for benign
      diseases.
AB  - PURPOSE: An evaluation was made of sexual and bladder dysfunction combined with
      quality of life (QoL) score after a proctocolectomy with total mesorectal
      excision (TME) for benign diseases. METHODS: An in-depth questionnaire was mailed
      to all patients (n = 94) who had undergone a proctocolectomy with TME followed by
      an ileal pouch-anal anastomosis (IPAA) in the period from 1989 through 1994.
      Seventy-six patients responded (81%) with a mean age of 34 +/- 10.6 years and a
      mean follow-up of 33 +/- 18.3 months. RESULTS: Sexual activity, satisfaction and
      libido were preserved better in males than in females. Severe sexual dysfunction
      was found in two males (permanent retrograde ejaculation) and in one female
      (complete vaginal dryness). No severe bladder dysfunction was found, although
      minor dysfunction, such as stress and urge incontinence, occurred frequently. QoL
      was significantly increased postsurgery. Moreover, no evident correlation was
      demonstrated between QoL and sexual and bladder dysfunction. CONCLUSION: A
      relatively low incidence of severe sexual and bladder disorders was found
      following proctocolectomy with TME and IPAA, whereas minor dysfunction was a
      relatively common finding. Nevertheless, a significant increase was found in
      postoperative QoL compared to preoperative QoL.

PMID- 11232493
TI  - Recent clinical developments in pathophysiology, epidemiology, diagnosis and
      treatment of intra-abdominal adhesions.
AB  - Postsurgical intra-abdominal adhesions pose a significant medical problem in the
      Western world, and in the past decade progress has been made in understanding
      their pathophysiology. The early balance between fibrin formation and degradation
      in the peritoneal cavity during and after surgery seems to be a major determinant
      of adhesion formation. Postsurgical inhibition of fibrinolytic activity severely
      impairs fibrin breakdown. Adhesive small-bowel obstruction, inadvertent
      enterotomy at reoperation, prolonged operative time dividing adhesions, increased
      clinical workload and high financial costs are important adhesion-related
      problems discussed in this review. The cumulative risk of adhesive small-bowel
      obstruction after (sub)total colectomy is 11% within 1 year, increasing to 30% at
      10 years. One of five patients undergoing reoperation suffers from inadvertent
      enterotomy, resulting in significant postoperative morbidity and mortality.
      Roughly 3% of all surgical admissions are associated with intra-abdominal
      adhesions. Clinical prospective trials have recently been designed to investigate
      the efficacy of barrier membranes and gels in the reduction of abdominal and
      pelvic adhesions and prevention of long-term morbidity, e.g., adhesive bowel
      obstruction and infertility in women. Early results are promising and contribute
      to the increased interest among clinicians in postsurgical adhesion formation and
      its consequences.

PMID- 11232494
TI  - Surgical treatment of morbid obesity: role of the gastroenterologist.
AB  - AIM: Obesity is an increasing medical problem with associated disorders such as
      type 2 diabetes mellitus, cardiovascular disorders and many others. The chance to
      develop co-morbidity is related to the body mass index (BMI) (weight in kg
      divided by height in metres2) and increases exponentially when the BMI is above
      40 (morbid obesity). Permanently effective treatment of morbid obesity is
      necessary to prevent the development of co-morbidities and to improve the life
      expectancy of these patients. To date, surgical intervention is the only
      treatment that can provide the required long-lasting reduction of the excess
      weight. DISCUSSION: Two types of surgical intervention are currently used,
      restrictive (including vertical banded gastroplasty (VBG) and adjustable gastric
      banding) and malabsorptive procedures (gastric bypass, biliopancreatic diversion
      (BPD)). These interventions effectively reduce weight, with on average a
      permanent reduction of the excess weight by 60% after gastric restrictive
      procedures. However, long-term follow-up has shown that up to 30-40% of patients
      require additional surgical interventions to maintain the acquired weight loss.
      Long-term failures are dependent on the primary intervention. After VBG the most
      common problems are occlusion of the outlet by a foreign body, vertical staple
      line disruption, band stenosis and band erosion. For the adjustable silicone
      gastric band outlet problems similar to the VBG, band erosion and particularly
      pouch dilation or slippage have been reported. Failure of the gastric bypass are
      mainly due to stenosis of the gastro-jejunostomy and stoma ulcers, whereas BPD
      mainly has metabolic long-term complications. CONCLUSION: The gastroenterologist
      has an important role in the diagnosis (stoma stenosis, band erosion, staple line
      disruption, foreign body) and treatment (dilatation, removal of foreign body) of
      the complications associated with surgical procedures for morbid obesity. In
      light of the increasing number of procedures performed, a basic knowledge of the
      currently used techniques and the associated complications is important.

PMID- 11232495
TI  - Clinical aspects of small-bowel transplantation.
AB  - AIM: To update clinical aspects of small-bowel transplantation. METHODS: Critical
      review of the literature. RESULTS: The two major functions of the small bowel are
      absorption of food and protection of the body against ingested pathogens. The
      highly developed immune system of the bowel, necessary for the latter function,
      prevented successful small-bowel transplantation during the 1960s and 1970s by
      provoking early and severe rejection of the graft. The introduction of
      cyclosporin in the 1980s enabled small-bowel transplantation with a moderate
      success rate. Further improvement of immunosuppressive regimens, especially the
      introduction of tacrolimus and aggressive surveillance for and treatment of
      infections, has resulted in a slow but steady improvement of transplant results
      during the past decade. At this moment, however, long-term parenteral nutrition
      is still the first-line treatment of the short-bowel syndrome world-wide because
      of the excellent results with regard to patient survival. CONCLUSION: Although
      results of small-bowel transplantation are steadily improving, especially due to
      better immunosuppressive regimens, long-term parenteral nutrition is still the
      first-line treatment of short-bowel syndrome.

PMID- 11232496
TI  - Changing perspectives in portal vein thrombosis.
AB  - The aetiology of portal vein thrombosis (PVT) is heterogeneous. Important primary
      risk factors for PVT are cirrhosis, hepatobiliary malignancies and pancreatitis.
      Newly discovered thrombotic risk factors, such as latent myeloproliferative
      disorders and prothrombotic genetic defects, have also been identified as major
      risk factors for PVT. At least one-third of PVT patients demonstrate a
      combination of thrombotic risk factors. PVT, which does not have a detrimental
      effect on liver function, usually becomes manifest as a variceal haemorrhage in
      the oesophagus months to years after the development of thrombosis. Owing to
      intact coagulation variceal bleeding has a better prognosis among patients with
      PVT than cirrhotics. Endoscopic sclerotherapy or band ligation is the primary
      therapeutic option for variceal bleeding in patients with PVT. It is questionable
      whether anticoagulant therapy should be started, since it has not proven
      beneficial for most PVT patients. Therapy with anticoagulants is only recommended
      for those with acute PVT (especially in association with mesenteric vein
      thrombosis), those who recently underwent a portosystemic shunt procedure, and
      those with other thrombotic manifestations, particularly in case of proven
      hypercoagulability. Mortality of patients with PVT may be associated with
      concomitant medical conditions which lead to the PVT or with manifestations of
      portal hypertension, such as variceal haemorrhage. Multivariate analysis of a
      large Dutch PVT population has shown that age, malignancy, ascites and the
      presence of mesenteric vein thrombosis are independently related to survival.
      Death due to a variceal haemorrhage is rare. Poor outcome of PVT thus appears to
      be associated primarily with concomitant diseases which lead to PVT, and not the
      complications of portal hypertension. It is therefore uncertain whether surgical
      portosystemic shunting affects survival favourably.

PMID- 11232497
TI  - Contrasting patterns of response to lamivudine monotherapy in chronic hepatitis B
      patients.
AB  - In this paper we describe a cohort of patients treated with lamivudine, a reverse
      transcriptase inhibitor with a strong virus-suppressive effect on the hepatitis B
      virus. Eighty-nine patients were included in the intention-to-treat analysis.
      Evaluation with the Kaplan-Meier method was based on response to therapy of HBV
      DNA levels as well as normalization of transaminases. Subgroup evaluation based
      on the per protocol data was performed on two groups within this cohort based on
      the HBV DNA level at the end of therapy. During a 52-week treatment period, the
      chance of being HBV DNA negative at one point in time, as measured by the Digene
      Hybrid Capture assay (HCS) (limit of detection 1.5 x 10(6) geq/ml), the
      quantitative PCR assay (Q PCR) (limit of detection 1000 geq/ml), or the chance of
      normalization of transaminases at one point in time is 78%, 57% and 66%,
      respectively. Nineteen out of 73 patients who had continuing active viral
      replication after at least 24 weeks of lamivudine therapy were evaluated for the
      emergence of mutations resistant to lamivudine. In 3 out of 19 patients a
      mutation in the highly conservative YMDD region of the polymerase gene was
      detected. Baseline viral load in this group was significantly higher compared to
      the other 54 patients who were treated for 24 weeks or longer. Thirty-one out of
      73 patients (46%) became negative by Q PCR. HBV DNA level at start of treatment
      was significantly lower compared to the 42 patients who remained HBV DNA
      positive. Eleven consecutive patients within this group who became negative by
      qualitative PCR (limit of detection 400 geq/ml) were evaluated to obtain
      characteristics for lamivudine withdrawal. Ten out of 11 patients became HBeAg
      negative with anti-HBe in 6. HBeAg in the liver biopsy was negative in 10 out of
      11 patients; 9 out of 10 obtained biopsies were positive for HBV DNA, indicating
      low-level viral replication. In two patients in whom lamivudine was withdrawn,
      rebound of virus occurred. Further research is needed to obtain better insight
      into the variability in response. This might lead to a tailor-made individualized
      treatment regimen.

PMID- 11232498
TI  - Erythropoietic protoporphyria. An overview with emphasis on the liver.
AB  - BACKGROUND: Erythropoietic protoporphyria (EPP) is an inherited disorder of heme
      synthesis, causing excess of protoporphyrin in blood, skin, liver and other
      organs. Protoporphyrin accumulation causes rapidly progressive liver failure in a
      minority of patients. Many questions concerning liver disease in EPP patients
      remain to be solved. METHODS: Review and update of the literature on EPP,
      protoporphyrin and hepatic involvement. RESULTS: The protoporphyrin molecule can
      be excited by absorbing light energy. This causes generation of free radicals and
      thereby photosensitivity of all tissues exposed to light. In the dark, several
      other toxic mechanisms have been described: deposition of protoporphyrin crystals
      in hepatocytes and bile canaliculi, interference with redox systems and,
      recently, formation of cytotoxic bile. Clinical manifestations of EPP are
      photosensitivity, insignificant hematological abnormalities and liver disease.
      The hepatic manifestations of the disease are diverse: mildly disturbed liver
      enzymes in 20% to fatal hepatic failure in less than 5%. End-stage protoporphyric
      liver failure and liver transplantation are complicated by severe
      photosensitivity, hemolysis, abdominal pains and neurological dysfunction. To
      make liver transplantation a safe procedure, special requirements have been
      proposed. Long-term survival after liver transplantation for EPP has been
      documented, but does not cure the disease.

PMID- 11232499
TI  - Cholestatic liver diseases: slow progress in understanding and treating slowly
      progressive disorders.
AB  - BACKGROUND: Cholestatic liver diseases are characterized by failure of normal
      amounts of physiological bile to reach the gastrointestinal tract. Any
      interference with normal bile flow from the canalicular membrane of the
      hepatocyte to the distal common bile duct may result in cholestasis. METHODS:
      Literature review. RESULTS: In primary biliary cirrhosis (PBC), the small
      intrahepatic bile ducts are destructed, resulting in obstruction of intrahepatic
      bile flow, whereas extrahepatic and/or intrahepatic biliary strictures block the
      passage of bile towards the intestine in primary sclerosing cholangitis (PSC). In
      contrast, the biliary tree is morphologically unaffected in less common
      cholestatic liver diseases as benign recurrent intrahepatic cholestasis (BRIC)
      and progressive familiar intrahepatic cholestasis (PFIC1-4). Genetic defects in
      hepatic canalicular transport mechanisms and bile salt synthesis deficiencies
      seem to underlie these types of cholestatic disorders. CONCLUSION: Recent
      advances in understanding and treatment of cholestatic liver diseases may help in
      better diagnosing and treating the various conditions characterized by
      cholestasis.

PMID- 11232501
TI  - Should you join a clinical trial?

PMID- 11232500
TI  - Gene therapy for gastrointestinal tract cancer: a review.
AB  - Carcinomas of the gastrointestinal tract count as one of the most common causes
      of cancer-related death in the world. Despite improvement of conventional
      treatment modalities, the prognosis of patients with gastrointestinal tract
      cancer remains poor. Progress in understanding the molecular mechanism of
      gastrointestinal carcinogenesis may facilitate development of gene therapy
      strategies for the treatment of gastrointestinal tumors. This review describes
      new developments in vectors (tools for gene transfer) for gene therapy, possible
      therapeutic genes and the early clinical results of gastrointestinal tract cancer
      gene therapy. Results of current preclinical studies are promising for the future
      clinical application of gene therapy for gastrointestinal cancer. The first
      clinical trials have been initiated recently, the preliminary results reflecting
      low toxicity and clinical responses. Further clinical studies will be required to
      confirm the feasibility of gene therapy in the treatment of gastrointestinal
      cancer. In future, the greatest potential will probably lie in the field of
      combination strategies of gene therapy and existing treatment modalities, such as
      surgery combined with molecular chemotherapy.

PMID- 11232502
TI  - Unexpected benefits of thyroid screening.

PMID- 11232503
TI  - Detecting an aortic bulge before it bursts.

PMID- 11232504
TI  - A promising new method for staging breast cancer.

PMID- 11232506
TI  - How can I stop the hiccups?

PMID- 11232505
TI  - Are artificial sweeteners safe?

PMID- 11232507
TI  - The natriuretic peptides: physiology and role in left-ventricular dysfunction.
AB  - The natriuretic peptides (NPs), atrial natriuretic peptide, and brain natriuretic
      peptide (BNP) have been shown to have important roles in fluid volume homeostasis
      and blood pressure regulation. In addition, plasma NP levels are elevated in a
      number of cardiac pathologies and have been used as biochemical markers of left
      ventricular dysfunction (LVD) in small- and large-scale clinical studies. In this
      review, the authors describe NP physiology and summarize the findings of selected
      studies that have examined the reliability and feasibility of NP measurement in
      LVD. In particular, BNP is proposed to be a biochemical marker that may provide a
      useful and inexpensive screening test of LVD. In addition, the authors discuss
      possible roles of the NPs in the etiology and progression of LVD. The findings of
      these studies suggest that the NPs may directly contribute to cardiac
      pathophysiology and LVD progression.

PMID- 11232508
TI  - Challenges facing research scientists.

PMID- 11232509
TI  - Understanding cytokines. Part I: Physiology and mechanism of action.
AB  - This is the first of a 2-part article on understanding cytokines. Cytokines are
      intercellular signaling proteins released from virtually all nucleated cells that
      influence growth and cellular proliferation in a wide range of tissues. Cytokines
      have immune modulating effects and are understood to control most of the physical
      and psychological symptoms associated with infection and inflammation. Cytokines
      also influence reproduction and bone remodeling. Dysregulation of the cytokine
      cellular system has significant implications in the development of a variety of
      illnesses, including most autoimmune disorders, many diseases of the
      cardiovascular system, osteoporosis, asthma, and depression. For nurses to be
      adequately informed when caring for clients with chronic illnesses and to be
      sufficiently knowledgeable when evaluating client outcomes, an understanding of
      the physiology of cytokines, the occurrences of dysregulation, and the role of
      cytokines in health and illness is essential. In Part I of this review, cytokine
      physiology is presented, with an emphasis on characteristics, categories, and
      mechanism of action. Specific instances of cytokine function in health and
      disease and implications for nursing research and practice are presented in Part
      II.

PMID- 11232510
TI  - Understanding cytokines. Part II: Implications for nursing research and practice.
AB  - Cytokines are small signaling proteins released from a variety of cells that
      influence virtually every aspect of growth and development and every host
      response to infection, injury, and inflammation. Because of their widespread and
      potent effects across the life span, cytokines without a doubt influence nursing
      research and practice. From physiological and adaptive effects of cytokines to
      cytokine-induced diseases, nurses and nursing care are involved. Part II of this
      review highlights a few of the many examples of cytokines functioning in response
      to infection and inflammation, during the processes of reproduction, and in a
      variety of pathophysiological states. Implications for nursing research and
      practice are emphasized.

PMID- 11232511
TI  - Iron-overload cardiomyopathy: evidence for a free radical--mediated mechanism of
      injury and dysfunction in a murine model.
AB  - Iron-overload cardiomyopathy is a restrictive cardiomyopathy that manifests
      itself as systolic or diastolic dysfunction secondary to increased deposition of
      iron in the heart and occurs with common genetic disorders such as primary
      hemochromatosis and beta-thalassemia major. Although the exact mechanism of iron
      induced heart failure remains to be elucidated, the toxicity of iron in
      biological systems is believed to be attributed to its ability to catalyze the
      generation of oxygen-free radicals. In the current investigation, the dose
      dependent effects of chronic iron-loading on heart tissue concentrations of iron,
      glutathione peroxidase (GPx) activity, free-radical production, and cardiac
      dysfunction were investigated in a murine model of iron-overload cardiomyopathy.
      It was shown that chronic iron-overload results in dose-dependent (a) increases
      in myocardial iron burden, (b) decreases in the protective antioxidant enzyme GPx
      activity, (c) increased free-radical production, and (d) increased mortality.
      These findings show that the mechanism of iron-induced heart dysfunction involves
      in part free radical-mediated processes.

PMID- 11232512
TI  - Methotrexate causes apoptosis in postmitotic endothelial cells.
AB  - Methotrexate (MTX) is a commonly used chemotherapy agent for a variety of
      cancers. However, therapeutic levels are associated with numerous untoward
      effects such as central nervous system damage in children with acute
      lymphoblastic leukemia. The purpose of this study was to determine if MTX caused
      injury to endothelial cells using cultured bovine pulmonary artery endothelial
      cells as a model. Light microscopy showed gaps between cells and reduced numbers
      of endothelial cells after exposure to MTX (10(-9) to 10(-5) M), a range
      consistent with therapeutic drug levels. Proliferation and viability of
      subconfluent and confluent MTX-treated endothelial cells were measured by
      colorimetric (MTS) assay. There was a significant decline in cell numbers in MTX
      treated subconfluent (growing) cells cultured after 4 days of MTX exposure
      compared to controls, as expected. However, there was also an unexpected decline
      in cell numbers in MTX-treated postmitotic endothelial cells after 1, 3, and 4
      days of drug exposure. This suggested that MTX induced endothelial cell death.
      Fluorescent ApoAlert Enhanced Annexin-V binding demonstrated apoptosis in
      endothelial cells after 1 day of MTX exposure. Apoptosis was confirmed by a DNA
      fragment assay. This is apparently the first report of MTX-induced apoptosis of
      postmitotic, cultured endothelial cells. The findings suggest that apoptosis may
      be one mechanism of MTX-induced injury to endothelial cells.

PMID- 11232513
TI  - Kangaroo care compared to incubators in maintaining body warmth in preterm
      infants.
AB  - Many preterm infants cared for in incubators do not experience Kangaroo Care
      (KC), skin-to-skin contact with their mothers, due to fear of body heat loss when
      being held outside the incubator. A randomized clinical trial of 16 KC and 13
      control infants using a pretest-test-posttest design of three consecutive
      interfeeding intervals of 2.5 to 3.0 h duration each was conducted over 1 day.
      Infant abdominal and toe temperatures were measured in and out of the incubator;
      maternal breast temperature was measured during KC. Repeated measures ANOVA
      showed no change in abdominal temperature across all periods and between groups.
      Toe temperatures were significantly higher during KC than incubator periods, and
      maternal breast temperature met each infant's neutral thermal zone requirements
      within 5 min of onset of KC. Preterm infants similar to those studied here will
      maintain body warmth with up to 3 h of KC.

PMID- 11232514
TI  - Crossing boundaries: making connections. Presidential address to the ISHN
      (International Society for the History of the Neurosciences), Lausanne, 1999.
AB  - This Presidential address to the International Society for the History of the
      Neurosciences was given at Lausanne in September 1999. It reviews some of the
      contributions given at that conference and provides a brief overview of the
      history of the mind-brain problem in Western neuroscientific thought.

PMID- 11232515
TI  - Proceedings of the fourth annual meeting of the European Association for the
      History of Psychiatry (EAHP), the European Club for The History of Neurology
      (ECHN), and the International Society for the History of the History of the
      Neurosciences (ISHN).

PMID- 11232516
TI  - Fritz Lewy and his bodies.
AB  - Attention is drawn to the neuronal inclusion bodies in Parkinsonism and the
      dementia described by F. Lewy in 1910, resulting in his eponym, as well as to his
      academic career and participation in two world wars on opposite sides.

PMID- 11232521
TI  - On the first systematic descriptions of botulism and botulinum toxin by Justinus
      Kerner (1786-1862).

PMID- 11232522
TI  - [Medical ethics nowadays].

PMID- 11232523
TI  - [Bicycle exercise test, Holter ECG monitoring and hyperventilation test in
      diagnosis coronary arteries stenosis in postmyocardial infarction patients].
AB  - To assess contribution of dynamic (vasospastic) stenosis to pathogenesis of
      anginal attacks in postmyocardial patients, 148 patients 15-4 months after the
      infarction were examined using bicycle exercise, Holter ECG monitoring and
      hyperventilation test (HVT). The relations between painless myocardial ischemia
      and vasospastic reactions in the course of hyperventilation were also studied.
      The ECG segment ST responded similarly in 97% of the patients. In positive HVT
      there was a slight rise in the heart rate and double product. Vasospastic
      reactions prevailed in the disease aggravation. Dynamic stenosis in
      postmyocardial patients is characterized by significant variability of ischemia
      threshold and total duration of ischemic episodes more than 30 minutes for 24
      hours.

PMID- 11232524
TI  - [Clinical features of gastrointestinal diseases in patients with primary mitral
      prolapse].
AB  - Whether patients with mitral prolapse (MP) have specific features in the course
      of their gastrointestinal diseases (GD) was studied in 420 MP patients with
      various GD. Echocardiography and examination of the vegetative status were
      conducted in all the patients. On demand, esophagogastroduodenoscopy, ultrasonic
      investigation of the abdominal organs, multistage fraction duodenal intubation
      were made. The findings evidence of more severe course of GD in MP patients. This
      manifests in early onset, severe pain and dispeptic syndromes, marked mucosal
      inflammation and is explained by dysfunction of the vegetative nervous system and
      generalized dysplasia of the connective tissue.

PMID- 11232526
TI  - [Actual diet of patients with gastrointestinal diseases].
AB  - The study of actual nutrition of patients with erosive-ulcerative lesions in the
      gastroduodenal zone and of patients with operated ulcer has revealed defects in
      intake of essential nutrients by these patients: overeating of animal fat and
      refined carbohydrates, deficiency of oil, vitamins A, B2, C, D and food fibers.

PMID- 11232525
TI  - [Endothelium-dependent vasodilation in patients with cerebrovascular disease].
AB  - The aim of the study was to examine changes in vasodilatory endothelial function
      in early cerebrovascular disease of atherosclerotic genesis. All the examinees
      underwent ultrasonic investigation, test for reactive hyperemia of the brachial
      artery to evaluate vasodilatory function of the endothelium. Disturbances in the
      flow-dependent vasodilation were detected at initial stages of the disease,
      aggravated with the progress of cerebrovascular disease and therefore could serve
      the earliest, objective indicator of atherosclerotic process.

PMID- 11232527
TI  - [Clinical variants and treatment of urological sepsis].
AB  - The paper describes current clinical features of urological sepsis, factors
      provoking sepsis in urological patients, leading laboratory and clinical
      characteristics of the disease, principles of treatment and its results.

PMID- 11232528
TI  - [Comparative study of retard and non-retard forms of isosorbide-5-mononitrate in
      coronary patients with stable angina pectoris].
AB  - An open cross-over trial compared retard and non-retard forms of isosorbide-5
      mononitrate (monomac 50D and isomonat, respectively) in 15 patients with stable
      angina of effort (functional class II-III). Both drugs were found rather
      effective, they significantly increase exercise tolerance. A single daily dose of
      monomac 50D reduced the number of anginal attacks. It was well tolerated, caused
      no serious side effects and had advantages over isomonat taken 2 or 3 times a
      day.

PMID- 11232529
TI  - [Capozide-50 alone and in combination with melatonin in therapy of hypertension].
AB  - Monotherapy with caposide-50 (C-50) was compared to combined therapy C-50 +
      melatonin in 22 patients with essential hypertension stage II (mean age 60
      years). The patients were divided into two groups. Group 1 received C-50 at 8.00
      a.m., group 2 received C-50 at 8.00 a.m. and melatonin at 10.00 p.m. in a dose 3
      mg. Before the treatment and 14 days after it echo-CG was made to assess
      hemodynamics. Also, 24-h monitoring of arterial pressure was performed. The
      findings were analysed with variance statistics and cosinor-analysis. Group 1
      achieved a moderate hypotensive effect. Circadian rhythm of systolic blood
      pressure was abnormal. Group 2 patients achieved more pronounced decline of
      systolic, diastolic and mean arterial pressures. Circadian rhythm of these
      pressure did not return to normal.

PMID- 11232530
TI  - [Diagnosis and treatment of mineral corticism].

PMID- 11232531
TI  - [Comparative effects of amlodipine (stamlo) and enalapril (enam) on arterial
      pressure, painless myocardial ischemia and diastolic function of left ventricle
      in patients with arterial hypertension].
AB  - 43 patients with mild and moderate arterial hypertension received monotherapy
      with either stamlo (Dr. Reddy's laboratories, India) in a daily dose 9.5 +/- 0.5
      mg (n = 33), or enam (n = 26) in a daily dose 28 +/- 1.5 mg, or stamlo treatment
      was followed in 10 days by enam (n = 16). Before and after the treatment 24-h
      monitoring was made of arterial pressure, left ventricular diastolic function and
      silent myocardial ischemia. Adequate lowering of arterial pressure was observed
      in 90 and 77% of patients after stamlo and enam treatment, respectively. Stamlo
      showed more potent antiischemic action and had a positive effect on left
      ventricular filling.

PMID- 11232532
TI  - [Reclid effects on carbohydrate, lipid metabolism, lipid peroxidation and
      hemodynamics in patients with diabetes mellitus type 2].
AB  - Patients with diabetes mellitus type II have disorders in carbohydrate, lipid and
      other kinds of metabolism. This increases the risk of cardiovascular
      complications and atherogenesis. Therefore, it is advisable to use drugs
      preventing an excessive late phase of insulin secretion with resultant reduction
      of hyperinsulinemia. Reclid, the drug of this group, improves metabolic
      processes, insulin resistance, lipid metabolism, hemostasis and microcirculation.
      3-month reclid therapy of patients with non-insulin-dependent diabetes mellitus
      produced a good hypoglycemic effect in 85% of the cases. This effect consisted in
      reduction of basal and postprandial glycemia, levels of glycosylated hemoglobin,
      24-h glucosuria. In patients with diabetes mellitus type II reclid diminished the
      levels of total cholesterol, triglycerides, glycosylated hemoglobin. In patients
      with left ventricular diastolic dysfunction, reclid improved transmitral blood
      flow. Thus, reclid provides a good metabolic control in patients with non-insulin
      dependent diabetes mellitus. Moreover, it positively affects mechanisms
      initiating cardiovascular complications in diabetic patients.

PMID- 11232533
TI  - [Hospital abstinence syndrome].

PMID- 11232534
TI  - [Bartter's syndrome with hyperuricemia and nephrocalcinosis].

PMID- 11232535
TI  - [A case of chronic post-embolic pulmonary hypertension].

PMID- 11232537
TI  - [The idea of staged clinical education. Events of 1840-1841].

PMID- 11232536
TI  - [How to define in diagnosis endoscopically detected lesions of gastrointestinal
      mucosa which arose in th time of administration of nonsteroidal antiinflammatory
      drugs?].

PMID- 11232538
TI  - [Inflammatory and immune responses of gastric mucosa on Helicobacter pylori
      infection].

PMID- 11232539
TI  - Dissociation of two kinds of source attributions.
AB  - We examined the relationship between two different source attribution errors. One
      error found primarily in the cognitive psychology literature is the belief that
      one is an author of an idea when one is not. The other error, reported in the
      social psychology literature, occurs when people overestimate how long they have
      known an idea. Although somewhat different, both errors are a form of
      misappropriation of ideas to oneself. We investigated both attributions and found
      that when participants performed a more elaborate encoding task, erroneous claims
      of authorship were reduced but length-of-knowing judgments increased. The results
      are discussed in terms of the cognitive processing that is likely to give rise to
      each source attribution.

PMID- 11232540
TI  - [Mucinosis follicularis in association with cutaneous T-cell lymphoma].

PMID- 11232541
TI  - [Vasculitis related to antineutrophil cytoplasmic antibodies to myelo peroxidase
      in a patient heterozygous for factor V Leiden mutation].

PMID- 11232542
TI  - [Disseminated infection with Mycobacterium asiaticum].

PMID- 11232543
TI  - [Buruli ulcer].

PMID- 11232544
TI  - [Newborn infant with congenital lamellar ichthyosis; 'collodion baby'].

PMID- 11232545
TI  - Case 8--2000. Intraoperative bispectral index monitoring and early extubation
      after cardiac surgery in patients with a history of awareness under anesthesia.

PMID- 11232546
TI  - Literature alerts.

PMID- 11232547
TI  - [Endovascular stent-graft placement for the treatment of thoracic aortic
      aneurysm].

PMID- 11232548
TI  - A severe complication of retroperitoneoscopic nephrectomy.

PMID- 11232549
TI  - Soleus stretch reflex during cycling.
AB  - The modulation and strength of the human soleus short latency stretch reflex was
      investigated by mechanically perturbing the ankle during an unconstrained
      pedaling task. Eight subjects pedaled at 60 rpm against a preload of 10 Nm. A
      torque pulse was applied to the crank at various positions during the crank
      cycle, producing ankle dorsiflexion perturbations of similar trajectory. The
      stretch reflex was greatest during the power phase of the crank cycle and was
      decreased to the level of background EMG during recovery. Matched perturbations
      were induced under static conditions at the same crank angle and background
      soleus EMG as recorded during the power phase of active pedaling. The magnitude
      of the stretch reflex was not statistically different from that during the static
      condition throughout the power phase of the movement. The results of this study
      indicate that the stretch reflex is not depressed during active cycling as has
      been shown with the H-reflex. This lack of depression may reflect a decreased
      susceptibility of the stretch reflex to inhibition, possibly originating from
      presynaptic mechanisms.

PMID- 11232550
TI  - A new method for experimental simulation of EMG using multi-channel independent
      stimulation of small groups of motor units.
AB  - The experimental simulation method was based upon the separate activation of up
      to 10 small groups of motor units (MU) in an acute nerve-muscle preparation. The
      investigator was able to precisely control and systematically alter the features
      of MU pool activation strategies. No implicit assumptions were made regarding MU
      properties. The purpose of this study was to evaluate the validity of this
      method. Three criteria were formulated and found to be satisfied: First, in the
      time domain, visual and audio displays of simulated EMG were indistinguishable
      from physiological EMG. Secondly, in the frequency domain, power spectra of
      simulated EMG revealed the typical features of EMG recorded during voluntary
      activation in the cat. Thirdly, the well-known monotonic relationship between EMG
      magnitude and force was readily reproduced, although strictly linear relations
      were not found. In addition, the relationship between the pool's ensemble
      activation rate and EMG magnitude showed distinct gain compression, mostly
      attributable to signal cancellation.

PMID- 11232551
TI  - Liver transplantation in a patient at psychosocial risk.
AB  - Psychosocial assessment of transplant candidates is a challenging task. Securing
      adequate information is made more difficult when patients present with fulminant
      hepatic failure. When the patient cannot be interviewed and the family is
      reluctant to provide vital information, a comprehensive pretransplant
      psychosocial evaluation is virtually impossible. However, even the most difficult
      cases have the potential for a positive result when a good psychosocial profile
      of the patient is obtained after transplantation, a team treatment plan is
      developed and carried out which addresses current and anticipated problems, and
      the patient obtains mental health treatment.

PMID- 11232552
TI  - Psychosocial assessments and outcomes in organ transplantation.
AB  - A qualitative review was conducted to define the term psychosocial as applied to
      transplant patients and to summarize evidence regarding the role and impact of
      psychosocial assessments and outcomes across the transplant process. English
      language case series and empirical studies from January 1970 through April 1990
      that were abstracted in Medline and Psychological Abstracts or listed in
      publications' bibliographies were used as data sources. A qualitative analysis
      was performed to determine the depth of the case reports and whether the
      empirical reports obtained statistically reliable, clinically significant
      findings. The authors conclude that psychosocial assessments differ in content
      and application to candidate selection depending on the transplant program.
      Psychosocial status before transplant does not consistently affect medical
      outcomes after transplant. Psychosocial status generally improves with
      transplant, although difficulties are prevalent in psychological adjustment and
      in compliance with medical regimens. Psychiatric history can predict
      psychological outcomes after transplant but does not consistently predict
      compliance. Social supports and coping strategies strengthen psychosocial
      outcomes. Posttransplant psychosocial outcomes may predict physical morbidity and
      mortality.

PMID- 11232553
TI  - William John Gies Award.

PMID- 11232555
TI  - Bibliography. Current world literature.  Gynecologic oncology and pathology.

PMID- 11232556
TI  - Professor Edward George Gray, FRS (1924-1999).
AB  - Professor George Gray, who died in August 1999, had a notable career as a pioneer
      electron microscopist of neural tissues. His name is still attached to synapses,
      which can be classified as Gray type 1 (symmetric) or type 2 (asymmetric), and in
      addition he made a number of other profound contributions to our knowledge of
      synaptic structures.He started his academic career late, having worked before the
      second World War as a bank clerk, and then serving in the Navy, patrolling for U
      boats in the North Sea and Atlantic for 4 years during the latter part of the
      war. He had an early interest in zoology, particularly in marine biology and
      microscopy and when he left the Navy he took the opportunity to work for a degree
      in Zoology at the University of Wales in Aberystwyth. A first class honours
      degree was followed by a PhD on melanophores in teleosts. It was fortunate that
      the external examiner for the thesis was J. Z. Young, who was impressed by the
      work and by George, and who invited George to work as his assistant in the
      preparation of The Life of the Mammals in the Anatomy Department at University
      College London.

PMID- 11232557
TI  - Oral steroids and inflammatory markers in asthma.

PMID- 11232558
TI  - Reliability of percentage ideal weight for height.

PMID- 11232560
TI  - Retrospective in science.   Louis Neel (1904-2000).

PMID- 11232561
TI  - Principles for the buffering of genetic variation.

PMID- 11232562
TI  - A decoherence-free quantum memory using trapped ions.
AB  - We demonstrate a decoherence-free quantum memory of one qubit. By encoding the
      qubit into the decoherence-free subspace (DFS) of a pair of trapped 9Be+ ions, we
      protect the qubit from environment-induced dephasing that limits the storage time
      of a qubit composed of a single ion. We measured the storage time under ambient
      conditions and under interaction with an engineered noisy environment and
      observed that encoding into the DFS increases the storage time by up to an order
      of magnitude. The encoding reversibly transfers an arbitrary qubit stored in a
      single ion to the DFS of two ions.

PMID- 11232564
TI  - High-energy physics.     Muon experiment challenges reigning model of particles.

PMID- 11232565
TI  - Russian science.  Danger to peer review is in eye of beholder.

PMID- 11232563
TI  - An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome.
AB  - Familial advanced sleep phase syndrome (FASPS) is an autosomal dominant circadian
      rhythm variant; affected individuals are "morning larks" with a 4-hour advance of
      the sleep, temperature, and melatonin rhythms. Here we report localization of the
      FASPS gene near the telomere of chromosome 2q. A strong candidate gene (hPer2), a
      human homolog of the period gene in Drosophila, maps to the same locus. Affected
      individuals have a serine to glycine mutation within the casein kinase Iepsilon
      (CKIepsilon) binding region of hPER2, which causes hypophosphorylation by
      CKIepsilon in vitro. Thus, a variant in human sleep behavior can be attributed to
      a missense mutation in a clock component, hPER2, which alters the circadian
      period.

PMID- 11232566
TI  - Ecological restoration.  NRC panel pokes holes in Everglades scheme.

PMID- 11232568
TI  - High-energy physics.  Nuclei crash through the looking-glass.

PMID- 11232567
TI  - Planetary science.  Caltech picks insider to lead JPL.

PMID- 11232569
TI  - Atmospheric chemistry.  Stratospheric 'rocks' may bode ill for ozone.

PMID- 11232570
TI  - Genome research.   Progress for the 'mouse gene encyclopedia'.

PMID- 11232571
TI  - Swiss science.   New program draws praise, complaints.

PMID- 11232572
TI  - Knot theory.     Loopy solution brings infinite relief.

PMID- 11232573
TI  - Ecology.  Scientists begin taming killer lake.

PMID- 11232574
TI  - Polygraph screening.  Panel seeks truth in lie detector debate.

PMID- 11232575
TI  - Marine biology. Keeping the stygian waters at bay.

PMID- 11232576
TI  - Marine biology.   Off Denmark, a drawn-out war against hypoxia.

PMID- 11232577
TI  - Marine biology.  The dead zone's fiercest crusaders.

PMID- 11232578
TI  - Aviation.  Dirigibles to grace skies over Germany once again.

PMID- 11232579
TI  - Millimeter astronomy.  U.S.-Mexican telescope gains firmer footing.

PMID- 11232580
TI  - Discovery of earliest hominid remains.

PMID- 11232581
TI  - Discovery of earliest hominid remains.

PMID- 11232582
TI  - Wording blurs survey on animal protection.

PMID- 11232583
TI  - The real power of artificial markets.

PMID- 11232584
TI  - Science and business. Conflicts of interest--moving beyond disclosure.

PMID- 11232586
TI  - Materials science.  The simplicity of complexity--rational design of giant pores.

PMID- 11232585
TI  - Cell biology.   A lipid oils the endocytosis machine.

PMID- 11232587
TI  - Radioactivity.  Are protons leaving in pairs?

PMID- 11232589
TI  - Applied physics.  A new twist for magnets.

PMID- 11232588
TI  - Ecology and evolution.  The risk of extinction--what you don't know will hurt
      you.

PMID- 11232590
TI  - Redox regulation of cardiac and skeletal sarcoplasmic reticulum.

PMID- 11232591
TI  - Association of increased ubiquitinated proteins with cardiac apoptosis.
AB  - Intracellular proteases play an important role in the regulation of apoptosis. A
      study was performed to determine whether inhibition of the cardiac ATP-dependent
      ubiquitin 26S protease complex affects cardiomyocyte apoptosis. Isolated rat
      hearts were perfused for up to 80 min with Krebs-Henseleit buffer +/- the 26S
      proteasome inhibitor, MG132 (Z-leu-leu-leucinal). TUNEL-staining of hearts
      perfused with 25 microM MG132 for 50 min revealed a significant increase (p <
      0.05) in the apoptotic index from 1.1% to 15.5% when compared with control hearts
      perfused with buffer only. Histology of adjacent myocardial sections revealed no
      signs of necrotic or late apoptotic (nuclear condensation) changes, indicating
      that the TUNEL-positive nuclei were in the early stages of apoptosis. This early
      stage of apoptosis was associated with a significant (p < 0.05) reduction in
      cardiac function. There was a 63% decrease in the rate pressure product in hearts
      perfused with 25 microM MG132 as compared with a 35% decrease in control hearts
      over the 80-min perfusion period. Soluble ubiquitin-conjugated proteins, as
      detected by probing with a specific antibody to ubiquitin, were increased in
      MG132-treated hearts. In hearts perfused with 50 microM MG132, a greater
      accumulation of ubiquinated proteins was observed accompanied by a more rapid and
      greater reduction in hemodynamic function. These observations indicate that
      prolonged inhibition of the ubiquitin-26S-proteasome results in cardiomyocyte
      apoptosis accompanied by increased ubiquinated proteins, thus suggesting that
      accumulation of these abnormal proteins may act as a signal to activate the cell
      death program.

PMID- 11232592
TI  - Physical exercise-induced expression of inducible nitric oxide synthase and heme
      oxygenase-1 in human leukocytes: effects of RRR-alpha-tocopherol supplementation.
AB  - This study evaluated the effects of RRR-alpha-tocopherol (500 IU/day, 8 days) on
      in vivo cytokine response and cytoplasmic expression of inducible nitric oxide
      synthase (iNOS) and the antioxidant stress protein heme oxygenase-1 (HO-1) in
      human leukocytes after exhaustive exercise. Thirteen men were investigated in a
      double-blind, placebo-controlled, cross-over study with a wash-out period of 28
      days. The exercise procedure consisted of an incremental treadmill test followed
      by a continuous run until exhaustion at 110% of the individual anaerobic
      threshold (total duration 28.5 +/- 0.8 min). HO-1 and iNOS protein were assessed
      in mono- (M), lympho-, and granulocytes (G) using flow cytometry. Plasma
      interleukin-6 (IL-6) and IL-8 were measured by ELISA. IL-6 rose significantly
      whereas IL-8 did not exhibit significant changes after exercise. Changes of IL-6
      were not affected by RRR-alpha-tocopherol. Exercise induced an increase of iNOS
      protein primarily in M and G. A small, but significant, increase of HO-1 protein
      was measured in M and G. RRR-alpha-Tocopherol did not show any significant
      effects on cytoplasmic expression of iNOS and HO-1 at rest and after exercise. In
      conclusion, exhaustive exercise induces expression of iNOS and HO-1 in human
      leukocytes by a mechanism that is not sensitive to RRR-alpha-tocopherol
      supplementation.

PMID- 11232593
TI  - Formation of 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal-modified
      proteins in rat liver after ischemia-reperfusion: distinct localization of the
      two oxidatively modified products.
AB  - Ischemia-reperfusion (IR) injury is an intractable process associated not only
      with therapeutic recanalization of vessels, but also with partial resection or
      transplantation of solid organs including liver. To develop methods for
      predicting the degree of hepatic IR injury and further to identify injured cells,
      we studied the formation of 8-hydroxy-2'-deoxy-guanosine (8-OHdG) and 4-hydroxy-2
      nonenal (HNE)-modified proteins in the normothermic hepatic IR model of rats
      using immunohistochemistry, high-performance liquid chromatography (HPLC)
      determination and Western blot. The Pringle maneuver for either 15 or 30 min
      duration produced reversible or lethal damage, respectively. The levels of both
      products were significantly increased in proportion to ischemia duration 40 min
      after reperfusion, suggesting the involvement of hydroxyl radicals. Increased
      immunoreactivity of 8-OHdG was observed not only in the nuclei of hepatocytes but
      also in those of bile canalicular and endothelial cells. However,
      immunoreactivity of HNE-modified proteins was detected in the cytoplasm of
      hepatocytes, which was confirmed by Western blot, and in addition, in the nuclei
      of hepatocytes after severe injury. Thus, localization of the two oxidatively
      modified products was not identical. Our data suggest that these two products
      could be used for the assessment of hepatic IR injury in tissue, but that the
      biological significance of the two products might be different.

PMID- 11232594
TI  - Evidence for a novel heme-binding protein, HasAh, in Alzheimer disease.
AB  - Multiple lines of evidence indicate that oxidative stress is an integral
      component of the pathogenesis of Alzheimer disease (AD). The precipitating cause
      of such oxidative stress may be misregulated iron homeostasis because there are
      profound alterations in heme oxygenase-1 (HO-1), redox-active iron, and iron
      regulatory proteins. In this regard, HasA, a recently characterized bacterial
      protein involved in heme acquisition and iron metabolism, may also be important
      in the generation of reactive oxygen species (ROS) given its ability to bind heme
      and render iron available for free radical generation through the Fenton
      reaction. To study further the role of heme binding and iron metabolism in AD, we
      show an abnormal localization of anti-HasA to the neurofibrillary pathology of
      AD, but not in normal-appearing neurons in the brains of cases of AD or in age
      matched controls. These results suggest the increased presence in AD of a HasA
      homologue or protein sharing a common epitope with HasA, which we term HasAh. We
      conclude that heme binding of HasAh is a potential source of free soluble iron
      and therefore toxic free radicals in AD and in aging. This furthers the evidence
      that redox-active iron and subsequent Fenton reaction generating reactive oxygen
      are critical factors in the pathogenesis of AD.

PMID- 11232595
TI  - Functional role of hyperreactive sulfhydryl moieties within the ryanodine
      receptor complex.
AB  - Several laboratories using chemically heterogeneous sulfhydryl modifying agents
      have shown that sarcoplasmic reticulum (SR) Ca2+ channels known as ryanodine
      receptors (RyRs) are especially sensitive to modification of functionally
      important cysteine residues. The functional consequence of sulfhydryl
      modification of RyRs can include phases of activation and inhibition that are
      very much dependent on the concentration of the reagent used, the length of
      exposure, and the nature of the chemical reaction the reagent undertakes with
      sulfhydryl groups. Most challenging is understanding the relationship for how
      specific sulfhydryl moieties ascribe specific aspects of RyR function.
      Considering the structural complexity of the RyR complex with its associated
      proteins, this task is likely to be a formidable one. A small number of
      hyperreactive thiols have been shown to exist within the RyR complex. Their
      functional role does not appear to impact directly on channel gating. Rather
      hyperreactive cysteine (Cys) moieties may represent biochemical components of a
      redox sensor that conveys information about localized changes in redox potential
      produced by physiologic (e.g., glutathione, nitric oxide) and pathophysiologic
      (quinones, reactive oxygen species) channel modulators to the Ca2+ release
      process. The molecular and functional details of such a redox sensor remains to
      be elucidated.

PMID- 11232596
TI  - How many cysteine residues regulate ryanodine receptor channel activity?
AB  - RyRs contain 80-100 cysteine residues per subunit, of which approximately 25% are
      free for covalent modification, while the remainder are either modified or form
      intraprotein disulfides. Oxidizing and nitrosylating reagents have several
      effects on single RyR channel activity, which depend on the type of modifying
      reagent, the isoform of the RyR, and ligands bound to the channel. We present
      evidence here for four major classes of functional cysteine residues associated
      with RyR channels, i.e., two classes with free -SH groups that either activate or
      inhibit channels when covalently modified and two classes, with endogenous
      modification, that either inhibit or activate. Single-channel characteristics
      provide evidence for four discrete responses within the first activating class,
      two responses within the second inhibiting class and two types of response within
      the third endogenously modified class. All but one of these changes in channel
      properties depend on residues located on the cytoplasmic or membrane-associated
      domains of the RyR; the remaining response is confined to the luminal domain. If
      it is assumed that each type of response depends on a separate subclass of
      cysteine residue and that each subclass contains a minimum of one cysteine per
      subunit, our results suggest that there are at least nine cysteine residues per
      subunit with functional connections to the gating mechanism of RyR channels.
      These cysteine residues may be selectively modified under physiological and
      pathological conditions to regulate Ca2+ release from the sarcoplasmic reticulum
      and contraction.

PMID- 11232597
TI  - Oxidative modification of ion channel activity of ryanodine receptor.
AB  - The ryanodine receptor (RyR) is involved in the physiological Ca2+ release from
      the sarcoplasmic reticulum in both skeletal and cardiac muscles. The redox
      regulation is a plausible endogenous regulatory mechanism of the RyR. Sulfhydryl
      oxidation or S-nitrosylation of the cardiac RyR has been reported to activate the
      channel. Our laboratory demonstrated that hydroxyl radicals also activate the
      cardiac Ca2+-release channel activity, likely through the modification of
      sulfhydryl groups of the RyR.

PMID- 11232598
TI  - RyR1 modulation by oxidation and calmodulin.
AB  - Alteration of skeletal muscle function by reactive oxygen species and nitric
      oxide (NO) may involve regulation of the activity of the skeletal muscle Ca2+
      release channel (also known as RyR1). We have shown that oxidants can activate
      RyR1 and produce inter-subunit disulfide bonds. Both effects are prevented by
      pretreatment with either NO donors or N-ethylmaleimide under conditions that
      modify less than 5% of the total sulfhydryls on RyR1. Oxidation-induced
      intersubunit crosslinking can also be prevented by the binding of either Ca2+
      calmodulin or apocalmodulin to RyR1. Also, both Ca2+ calmodulin and apocalmodulin
      binding are blocked by oxidation of RyR1. In contrast, alkylation with N
      ethylmaleimide or reaction with NO donors preferentially blocks apocalmodulin
      binding to RyR1, suggesting the existence of a regulatory cysteine within the
      apocalmodulin binding site. We have demonstrated that Ca2+ calmodulin and
      apocalmodulin bind to overlapping, but nonidentical, sites on RyR1 and that
      cysteine 3635 is close to or within the apocalmodulin-binding site on RyR1. This
      cysteine is also one of the cysteines that form the intersubunit disulfide bonds,
      suggesting that calmodulin binds at an intersubunit contact site. Our findings
      are consistent with a model in which oxidants regulate the activity of RyR1
      directly by altering subunit-subunit interactions and indirectly by preventing
      the binding of either Ca2+-bound calmodulin or apocalmodulin. NO also has both a
      direct and an indirect effect: it blocks the ability of oxidants to generate
      intersubunit disulfide bonds and prevents apocalmodulin binding.

PMID- 11232599
TI  - Calmodulin and cyclic ADP-ribose interaction in Ca2+ signaling related to cardiac
      sarcoplasmic reticulum: superoxide anion radical-triggered Ca2+ release.
AB  - Reactive oxygen species (ROS) are often shown to damage cellular functions. The
      targets of oxidative damage depend on the nature of ROS produced and the site of
      generation. In contrast, ROS can also regulate signal transduction. In this case,
      ROS may either induce or enhance events, which lead to forward directions of
      cellular signaling. The consequences of regulation of signal transduction can be
      observed in physiological processes such as muscle contraction. Here, we discuss
      the concentration-dependent effects of superoxide anion radical (*O2-) on Ca2+
      release from the cardiac sarcoplasmic reticulum (SR). Recent studies suggest that
      the ADP-ribosyl cyclase pathway, through its production of cyclic adenosine 5'
      diphosphoribose (cADPR), may control Ca2+ mobilization in cardiac muscle cells.
      *O2- has dual effects that are concentration dependent. At low concentrations
      (nearly nanomolar levels), *O2- induces Ca2+ release by stimulating synthesis of
      cADPR, which requires calmodulin for sensitization of ryanodine-sensitive Ca2+
      release channels (RyRC). At these low concentrations, *O2- is responsible for
      regulation of cellular signal transduction. At higher concentrations (micromolar
      levels), *O2- produces a loss in the function of calmodulin that is to inhibit
      RyRC. This results in an increase in Ca2+ release, which is linked to cell
      injury. The difference in the functions of low and high concentrations of *O2-
      may result in two distinct physiological roles in cardiac muscle Ca2+ signaling.

PMID- 11232600
TI  - Molecular interaction between nitric oxide and ryanodine receptors of skeletal
      and cardiac sarcoplasmic reticulum.
AB  - In striated muscle, the sarcoplasmic reticulum (SR) is the major storage
      compartment of intracellular Ca2+ that controls cytosolic free Ca2+ (Cai) and
      developed force by sequestering and releasing Ca2+ during each contraction. Ca2+
      release from the SR occurs through high-conductance Ca2+ release channels or
      ryanodine receptors (RyR), which are regulated by various signaling processes.
      Over the last 15 years, there has been a growing consensus that critical
      sulfhydryl sites on RyRs can be oxidized and reduced, respectively, to open and
      close the release channels. The pharmacological actions of various classes of
      sulfhydryl reagents have demonstrated the existence of hyperreactive thiols on
      RyRs, which could play a role in the regulation of normal contractile function
      and explain contractile dysfunctions in pathological conditions. More recent
      studies show that redox regulation of release channels may occur by nitric oxide
      (NO), a physiological signaling mechanism. This article is intended to review
      current concepts in thiol regulation of RyRs and present new data on the possible
      identification of the primary cysteine residues, which may be the site of
      oxidation and S-nitrosylation involved in channel opening.

PMID- 11232601
TI  - Oxygen free radicals and excitation-contraction coupling.
AB  - Oxygen free radicals (OFR) contribute to contractile failure, rigor, and calcium
      (Ca2+) overload in ischemic/reperfused myocardium. Using both multicellular and
      isolated single-cell preparations, our laboratory has identified two fundamental
      mechanisms contributing to the deleterious effects of OFR: (i) impaired
      myocardial metabolism, and (ii) altered myocardial calcium handling. Impaired
      metabolism leads to activation of metabolically sensitive K+ currents, which
      shorten the action potential, thereby decreasing the duration of systole.
      Ultimately, high-energy phosphate depletion secondary to metabolic failure
      results in rigor. Altered myocardial Ca2+ handling is evidenced by a decrease in
      Ca2+ entry via L-type Ca2+ channels [another cause of decreased action potential
      duration (APD)], a reduction in sarcoplasmic reticulum (SR) Ca2+ content, slowed
      Ca2+ uptake in diastole, and increased sodium-calcium exchange (NaCaX) activity.
      The increase in NaCaX activity may contribute to the early increase in developed
      tension frequently observed in multicellular preparations exposed to free
      radicals, as well as the SR depletion occurring early on in voltage-clamped
      isolated cell preparations. Increased NaCaX activity is likely to be a critical
      factor underlying the late Ca2+ overload that occurs in the setting of increased
      intracellular Na+, and which leads to irreversible injury. The extent to which
      free radical-mediated metabolic inhibition participates in the dysfunction of the
      L-type Ca2+ channel is uncertain. The altered activity of the SR Ca2+ pump and
      NaCaX are more likely caused by direct actions of OFR on these proteins.

PMID- 11232602
TI  - Redox regulation of cardiac muscle calcium signaling.
AB  - Signal transduction for cardiac muscle contraction is regulated by the Ca2+
      induced Ca2+-release mechanism. Redox reactions by biological oxidants and
      antioxidants have been shown to alter the kinetics of Ca2+-induced Ca2+ release.
      We postulate that altered kinetics of Ca2+-induced Ca2+ release may divert the
      contractile pool of Ca2+ to elicit excitation-transcription coupling. We provide
      evidence that redox reactions regulate excitation-transcription coupling by
      showing that membrane depolarization may activate the GATA4 transcription factor
      only when the cells are pretreated with hydrogen peroxide. Therefore, redox
      regulation of the ryanodine receptor may serve as a mechanism to determine
      whether the contractile pool of Ca2+ should signal gene transcription during
      excitation-contraction coupling.

PMID- 11232603
TI  - Reversible thiol-dependent activation of ryanodine-sensitive Ca2+ release channel
      by etoposide (VP-16) phenoxyl radical.
AB  - Many phenolic compounds can act as antioxidants by donating a proton to peroxyl
      radicals and quenching lipid peroxidation. Phenoxyl radicals produced this way or
      from metabolism by peroxidases, tyrosinase, or mixed-function oxidases, however,
      may react with sulfhydryl groups of proteins and other endogenous thiols. In this
      regard, phenolic compounds may have cytotoxic potential instead of antioxidant
      effects. We employed the anticancer drug, etoposide (VP-16), as a model phenolic
      compound to study the sensitivity of ryanodine-sensitive Ca2+ channel (RyR) to VP
      16 phenoxyl radicals. The combination of VP-16 and tyrosinase, used to generate
      the etoposide phenoxyl radical, produced marked Ca2+ release from Ca2+-loaded RyR
      rich vesicles prepared from terminal cisternae fraction of sarcoplasmic reticulum
      (SR). This effect was reversed by the SH-reagent, dithiothreitol (DTT),
      suggesting that cysteines within the RyR-protein complex were targets for
      modification by VP-16 phenoxyl radicals. VP-16/tyrosinase-induced release of Ca2+
      was attenuated in vesicles prepared from longitudinal SR, which contain
      relatively little RyR. The effects of the VP-16 phenoxyl radical on Ca2+-ATPase
      in SR vesicles resembled those observed with caffeine or 4,4'-dithiodipyridine,
      both of which activate RyR Ca2+ release and lead to activation of Ca2+-ATPase via
      prolonged Ca2+ cycling. The addition of ruthenium red returned Ca2+-ATPase to its
      original level. Thus, under these conditions Ca2+-ATPase was not directly
      affected by VP-16 phenoxyl radical. The hypersensitive SH-groups on RyR are shown
      to be targets for oxidation of VP-16 phenoxyl radical, and suggest that other
      phenolic compounds could similarly disrupt Ca2+ homeostasis.

PMID- 11232604
TI  - Thioredoxin inhibits tumor necrosis factor- or interleukin-1-induced NF-kappaB
      activation at a level upstream of NF-kappaB-inducing kinase.
AB  - Gene induction by tumor necrosis factor-alpha (TNFalpha) or interleukin-1beta (IL
      1beta) is mediated in part by activation of the transcription factor nuclear
      factor kappaB (NF-kappaB), and requires signal adaptor molecules such as TNF
      receptor-associated factor (TRAFs). The latter interact with the NF-kappaB
      inducing kinase (NIK), which is believed to be part of the IkappaB kinase
      complex. Although the precise mechanism is to be elucidated, it is well-known
      that antioxidant treatments inhibit the inflammatory cytokine-induced NF-kappaB
      activation. Thioredoxin (TRX) is a 12-kDa endogenous protein that regulates
      various cellular functions by modulating the redox state of proteins,
      overexpression of this molecule inhibits NF-kappaB activation. To elucidate the
      roles of TRX in the signal transduction of the cytokines, we investigated the
      effects of TRX on NF-kappaB activation induced by cytokine treatment or by
      overexpression of the signaling molecules. Our data show that TRX treatment
      inhibits NF-kappaB-dependent transcription at the level of downstream of TRAFs
      and upstream of NIK: TRX inhibited TRAF2-, TRAF5-, and TRAF6-induced NF-kappaB
      activation but does not inhibit NIK-, IKKalpha-, and MEKK-induced activation. In
      addition, we show that TRX inhibits NF-kappaB activation in a manner different
      from that for SAPK (stress activated protein kinase) inhibition.

PMID- 11232606
TI  - Distribution of patients' paroxysmal atrial tachyarrhythmia episodes:
      implications for detection of treatment efficacy.
AB  - INTRODUCTION: Clinical trials of treatments for paroxysmal atrial tachyarrhythmia
      (pAT) often compare different treatment groups using the time to first episode
      recurrence. This approach assumes that the time to the first recurrence is
      representative of all times between successive episodes in a given patient. We
      subjected this assumption to an empiric test. METHODS AND RESULTS: Records of pAT
      onsets from a chronologic series of 134 patients with dual chamber implantable
      defibrillators were analyzed; 14 had experienced >10 pAT episodes, which is
      sufficient for meaningful statistical modeling of the time intervals between
      episodes. Episodes were independent and randomly distributed in 9 of 14 patients,
      but a fit of the data to an exponential distribution, required by the stated
      assumption, was rejected in 13 of 14. In contrast, a Weibull distribution yielded
      an adequate goodness of fit in 5 of the 9 cases with independent and randomly
      distributed data. Monte Carlo methods were used to determine the impact of
      violations of the exponential distribution assumption on clinical trials using
      time from cardioversion to first episode recurrence as the dependent measure. In
      a parallel groups design, substantial loss of power occurs with sample sizes <500
      patients per group. In a cross-over design, there is insufficient power to detect
      a 30% reduction in episode frequency even with 300 patients. CONCLUSION: Clinical
      trials that rely on time to first episode recurrence may be considerably less
      able to detect efficacious treatments than may have been supposed. Analysis of
      multiple episode onsets recorded over time should be used to avoid this pitfall.

PMID- 11232605
TI  - Oxidative stress and NF-kappaB activation: correlation in patients following
      allogeneic bone marrow transplantation.
AB  - Although in vitro data has linked reactive oxygen species (ROS) to activation of
      nuclear factor kappaB (NF-kappaB), little data exist regarding this relationship
      in human disease. We hypothesized that bone marrow transplantation (BMT) would
      impart a degree of oxidative stress that might lead to in vivo activation of the
      redox-sensitive transcription factor NF-kappaB. Because NF-kappaB regulates
      transcription of many proinflammatory mediators, we reasoned that activation of
      NF-kappaB might contribute to the development of transplant-related
      complications. To evaluate NF-kappaB activation in humans, we measured NF-kappaB
      binding activity in nuclear extracts of bronchoalveolar lavage (BAL) cells
      obtained before and after allogeneic bone marrow transplantation (BMT) in 7
      patients. Changes in BAL cell NF-kappaB binding activity were compared with
      changes in urinary F2-isoprostane concentration, an indicator of in vivo free
      radical-catalyzed lipid peroxidation. Although the extent of in vivo lipid
      peroxidation has substantial interindividual variability over time, we found a
      strong correlation between the pre/post-BMT ratio of urinary isoprostane
      concentrations and pre/post-BMT ratio of NF-kappaB binding activity in BAL cells,
      R = 0.96, p = 0.0005). This correlation is selective, because no relationship was
      found between the transcription factor CREB and urinary F2-isoprostane excretion.
      Although limited by the small number of patients studied, our data link oxidant
      stress to NF-kappaB activation in human alveolar macrophages following BMT. It is
      possible that such interactions may contribute to the clinical course after BMT
      by affecting transcription of proinflammatory genes.

PMID- 11232607
TI  - Modeling recurrent arrhythmias.

PMID- 11232608
TI  - Do current dual chamber cardioverter defibrillators have advantages over
      conventional single chamber cardioverter defibrillators in reducing inappropriate
      therapies? A randomized, prospective study.
AB  - INTRODUCTION: Supraventricular tachyarrhythmias are the main cause of
      inappropriate therapies in patients with conventional single chamber implantable
      cardioverter defibrillators (VVI-ICD). It was anticipated that dual chamber
      cardioverter defibrillators (DDD-ICD), with their capacity to analyze atrial and
      ventricular rhythm, could substantially reduce inappropriate therapies. METHODS
      AND RESULTS: Our prospective study included 92 patients (87 men; mean age 61 +/-
      12.7 years) who were randomly assigned to a VVI-ICD (45 patients) or a DDD-ICD
      (47 patients). Both groups were followed for 7.5 +/- 3.5 and 7.6 +/- 4.1 months,
      respectively. During the follow-up period, overall 725 ventricular tachycardia
      (VT)/ventricular fibrillation (VF) episodes were recorded in 45 (49%) of 92
      patients. Of these episodes, 404 (56%) occurred in the VVI-ICD group and 321
      (44%) episodes occurred in the DDD-ICD group. Twenty-three (51%) patients in the
      VVI-ICD group and 22 (47%) patients in the DDD-ICD group (P = 0.8) developed
      VT/VF. Overall, 73 (10%) of 725 treated episodes were inappropriate in 6 (13%)
      patients in the VVI group and in 10 (21%) patients in the DDD-ICD group (P =
      0.2). There were 22 (31%) inappropriately treated episodes in the VVI-ICD group
      and 51 (69%) in the DDD-ICD group. Thirty-two of the 51 inappropriate episodes in
      the DDD-ICD patients resulted from intermittent atrial sensing problems that led
      to failure of the respective dual chamber algorithms. Nonfatal complications
      occurred in 6 (13%) patients in the VVI-ICD group and in 3 (6%) patients in the
      DDD-ICD group (P = 0.7). CONCLUSION: We conclude that the implanted DDD-ICD and
      conventional VVI-ICD are equally safe and effective for therapy of life
      threatening ventricular tachyarrhythmias. Although DDD-ICDs allow better rhythm
      classification, the applied detection algorithms do not offer benefits in
      avoiding inappropriate therapies during supraventricular tachyarrhythmias.

PMID- 11232609
TI  - Inappropriate defibrillator therapies: are dual chamber devices providing a
      remedy?

PMID- 11232610
TI  - Use of correlation waveform analysis in discrimination between anterograde and
      retrograde atrial electrograms during ventricular tachycardia.
AB  - INTRODUCTION: Discriminating between ventricular tachycardia (VT) with 1:1
      ventriculoatrial association and sinus tachycardia can be difficult, even when
      assisted by intracardiac tracings. In this study, we used a new computer
      algorithm to perform correlation waveform analyses on intracardiac atrial
      electrograms to help distinguish between VT and sinus tachycardia. METHODS AND
      RESULTS: Electrophysiologic studies of 28 patients (22 men; age 66 +/- 14 years)
      with inducible VT and mean ejection fraction of 37% +/- 16% were analyzed. A
      template of an intracardiac high right atrial electrogram was obtained during
      sinus rhythm (SR). Atrial electrograms during SR and VT were compared with the
      template using the new algorithm, and correlation coefficients (rho) were
      generated. The correlation coefficient of SR beats with the template was 96.4% +/
      3.4%. During VT with AV dissociation and persistent SR, rho was 94.5% +/- 3.7%
      (P = NS). During VT with 1:1 retrograde conduction, rho was 70.6% +/- 11.3% (P <
      0.0001). At a cutoff of 85%, rho had positive and negative predictive values of
      99% and 96%, respectively. CONCLUSION: Our findings indicate that the new
      algorithm can reliably separate between anterograde and retrograde atrial
      activation during VT. It can, therefore, discriminate between sinus tachycardia
      and VT with 1:1 ventriculoatrial conduction and may be useful in preventing
      inappropriate shocks from dual chamber defibrillators.

PMID- 11232611
TI  - Correlation waveform analysis of the atrial signal: the shape of things to come?

PMID- 11232612
TI  - Use of a saline-irrigated tip catheter for ablation of ventricular tachycardia
      resistant to conventional radiofrequency ablation: early experience.
AB  - INTRODUCTION: Radiofrequency (RF) catheter ablation of ventricular tachycardia
      (VT) may fail if the critical isthmus is located intramyocardially or
      epicardially. The design of a saline-irrigated tip (SIT) catheter (Thermo-Cool,
      Cordis-Webster) involves active cooling of the tip electrode, which allows
      creation of larger ablation lesions. METHODS AND RESULTS: Eight patients (6 men,
      age 59 +/- 12 years) in whom the clinical target VT (cycle length 430 +/- 97
      msec) could not be ablated using a conventional 4-mm tip RF ablation catheter
      underwent additional attempts to ablate this VT using a SIT catheter. Six
      patients had an old myocardial infarction, 1 patient had a dilated
      cardiomyopathy, and 1 patient had a structurally normal heart. Ablation of the
      clinical target VT using a SIT catheter was attempted from the left ventricle in
      6 (septal, posterobasal, and inferior: 2 each) and from the right ventricle in 2
      patients (both septal), by entrainment (n = 6), activation (n = 1), or pace
      mapping (n = 1). A mean of 6 +/- 5 (range 2 to 15) pulses were delivered. Target
      VT ablation was successful in 5 patients (63%). After successful ablation, at a
      mean follow-up of 6.5 +/- 4 months and while taking antiarrhythmic drugs, all 5
      patients were free of VT recurrences. CONCLUSION: The clinical target VT could be
      ablated using a SIT catheter in 5 (63%) of the 8 patients in whom ablation using
      a conventional RF catheter was unsuccessful. In the 2 patients with septal VT, a
      biventricular approach to mapping and ablation was required.

PMID- 11232613
TI  - Implantable cardioverter defibrillator practices and costs at an academic medical
      center.
AB  - This study addresses current costs of implanting implantable cardioverter
      defibrillators (ICDs) at one large medical center and documents actual costs
      using two methodologies. To determine the actual cost of ICD therapy, we studied
      all ICD implants performed in the procedure room (similar to an electrophysiology
      laboratory) who met accepted secondary prevention (AVID) indications for a 1-year
      period at Loyola University Medical Center. The study period coincided with the
      facility's shift of this procedure out of the operating room to a procedure room.
      Costs were analyzed two ways: a cost-based analysis and a cost-to-charge ratio
      analysis based on the facility's Medicare Cost Report. Twenty-four patients (14
      inpatients and 10 outpatients) met the study inclusion criteria. Length of stay
      averaged 5.8 days for inpatients and 1.1 days for outpatients. In the cost-based
      analysis, the mean costs of the ICD implant (device, implant procedure, and
      preimplant and postimplant stay) were $33,509 for inpatient and $28,078 for
      outpatient implants. In the cost-to-charge ratio analysis, the mean costs for the
      inpatient hospitalization were $35,623. This is one of the first studies to
      document cost of ICD therapy and may serve as a benchmark for other facilities.

PMID- 11232614
TI  - Cost reduction and implantable cardioverter defibrillator implantation.

PMID- 11232615
TI  - Role of transisthmus conduction intervals in predicting bidirectional block after
      ablation of typical atrial flutter.
AB  - INTRODUCTION: Complete bidirectional cavotricuspid isthmus block is the endpoint
      for ablation of typical atrial flutter. The purpose of this study was to
      determine whether the extent of prolongation of the transisthmus interval after
      ablation predicts complete bidirectional block. METHODS AND RESULTS: Fifty-seven
      consecutive patients underwent 60 ablation procedures for isthmus-dependent
      atrial flutter. The clockwise and counterclockwise transisthmus intervals were
      determined before and after ablation during pacing from the low lateral right
      atrium and the coronary sinus. Bidirectional block was achieved with ablation in
      55 (96%) of 57 patients. The transisthmus intervals before ablation and after
      complete transisthmus block were 100.3 +/- 21.1 msec and 195.8 +/- 30.1 msec,
      respectively, in the clockwise direction (P < 0.0001), and 98.2 +/- 24.7 msec and
      185.7 +/- 33.9 msec, respectively, in the counterclockwise direction (P <
      0.0001). An increase in the transisthmus interval by > or = 50% in both
      directions after ablation predicted complete bidirectional block with 100%
      sensitivity and 80% specificity. The positive and negative predictive values were
      89% and 100%, respectively. The diagnostic accuracy of a > or = 50% prolongation
      in the transisthmus interval was 92%. CONCLUSION: Prolongation of the
      transisthmus interval by > or = 50% in the clockwise and counterclockwise
      directions is associated with a high degree of diagnostic accuracy and an
      excellent negative predictive value in determining complete bidirectional
      transisthmus block. This may be a useful and simple adjunctive criterion for
      assessment of complete transisthmus conduction block.

PMID- 11232616
TI  - Inhibition of K+ currents by homocysteine in rat ventricular myocytes.
AB  - INTRODUCTION: Clinical evidence suggests that increased blood levels of
      homocysteine may be an independent risk factor for the development of
      cardiovascular disease, but the functional effects of this sulfhydryl amino acid
      on the myocardium are poorly understood. The present study was conducted to
      determine the direct effects of homocysteine on the electrophysiologic properties
      of the heart. METHODS AND RESULTS: Whole-cell voltage-clamp recordings were made
      in ventricular myocytes isolated from normal rat hearts to analyze the Ca2+
      independent, transient outward K+ current (I(to)), a major repolarizing current
      in these cells. Maximum I(to) density (measured at +60 mV) was decreased
      approximately 47% from baseline in the presence of 500 microM homocysteine (P <
      0.05), but the amount of block varied in a frequency- and voltage-dependent
      manner. Decreased I(to) density was not accompanied by significant changes in
      voltage- or time-dependent properties of the current, nor was it affected by
      pretreating myocytes with the protein kinase inhibitor staurosporine. Because a
      portion of total extracellular homocysteine is oxidized, we examined the response
      to homocystine, the oxidized form of homocysteine. In myocytes superfused with
      500 microM homocystine, maximum I(to) density was decreased by approximately 40%
      from baseline (P < 0.05). In contrast, the thiolactone form of homocysteine did
      not alter I(to) amplitude. CONCLUSION: These data suggest that homocysteine and
      its oxidized form homocystine acutely inhibit I(to) channels in ventricular
      myocytes by mechanisms involving the free thiol or disulfide moieties of these
      compounds. High homocysteine or homocystine levels may contribute to abnormal
      repolarization and arrhythmogenic conditions in the intact heart.

PMID- 11232617
TI  - Redox modulation of cardiac electrical activity.

PMID- 11232618
TI  - Electrophysiologic perturbations and arrhythmogenic activity caused by activation
      of the Fas receptor in murine ventricular myocytes: role of the inositol
      trisphosphate pathway.
AB  - INTRODUCTION: Experimental evidence suggests a major role for Fas receptor
      activation in a wide range of myocardial pathologies. Because clinical
      situations, which are likely to be associated with Fas activation, are
      accompanied by a variety of ventricular arrhythmias, the major goal of this study
      was to investigate the ionic mechanisms responsible for these phenomena. METHODS
      AND RESULTS: To delineate the origin of Fas-mediated electrophysiologic
      perturbations, the transient outward K+ current I(to) and the L-type Ca2+ current
      I(Ca,L) were studied in murine ventricular myocytes treated with the Fas
      activating monoclonal antibody Jo2. Jo2 decreased I(to) (4.36 +/- 1.2 pA/pF vs
      17.48 +/- 2.36 pA/pF in control, V(M) = +50 mV; P < 0.001) and increased I(Ca,L)
      (-13.17 +/- 1.38 pA/pF vs -3.94 +/- 0.78 pA/pF in control, V(M) = 0 mV; P <
      0.001). Pretreatment of ventricular myocytes with ryanodine or thapsigargin
      prevented the electrophysiologic effects of Jo2, suggesting that [Ca2+]i
      elevation is important for Fas-mediated action. In agreement with our previous
      studies demonstrating dependence of Fas-based myocyte dysfunction on an intact
      inositol trisphosphate (1,4,5-IP3) pathway, the effects of Jo2 on I(to) and
      I(Ca,L) were prevented by the phospholipase C (generates 1,4,5-IP3) blocker
      U73122, and by xestospongin C (tested with I(to)), a specific blocker of IP3
      operated sarcoplasmic reticulum Ca2+ release channels. Furthermore, intracellular
      perfusion with 1,4,5-IP3, but not with 1,3,4-IP3, caused electrophysiologic
      effects resembling those of Jo2. CONCLUSION: Decreased I(to) and increased
      I(Ca,L) underlie Fas-induced action potential alterations and arrhythmias in
      murine ventricular myocytes, effects that appear to be mediated by 1,4,5-IP3
      induced intracellular calcium release.

PMID- 11232619
TI  - Mechanisms for discordant alternans.
AB  - INTRODUCTION: Discordant alternans has the potential to produce larger alternans
      of the ECG T wave than concordant alternans, but its mechanism is unknown.
      METHODS AND RESULTS: We demonstrate by one- and two-dimensional simulation of
      action potential propagation models that discordant alternans can form
      spontaneously in spatially homogeneous tissue through one of two mechanisms, due
      to the interaction of conduction velocity and action potential duration
      restitution at high pacing frequencies or through the dispersion of diastolic
      interval produced by ectopic foci. In discordant alternans due to the first
      mechanism, the boundaries marking regions of alternans with opposite phase arise
      far from the stimulus site, move toward the stimulus site, and stabilize. Dynamic
      splitting of action potential duration restitution curves due to electrotonic
      coupling plays a crucial role in this stability. Larger tissues and faster pacing
      rates are conducive to multiple boundaries, and inhomogeneities of tissue
      properties facilitate or inhibit formation of boundaries. CONCLUSION: Spatial
      inhomogeneities of electrical restitution properties are not required to produce
      discordant alternans.

PMID- 11232620
TI  - T wave alternans: a mechanism of arrhythmogenesis comes of age after 100 years.

PMID- 11232621
TI  - Topographic anatomy of the inferior pyramidal space: relevance to radiofrequency
      catheter ablation.
AB  - INTRODUCTION: Radiofrequency catheter ablation carried out in the vicinity of the
      triangle of Koch risks damaging not only the AV conduction tissues but also their
      arterial supply. The aim of this study was to examine the relationship of the AV
      nodal artery to the inferior pyramidal space, the triangle of Koch, and the right
      atrial endocardial surface. METHODS AND RESULTS: We studied 41 heart specimens,
      24 by gross dissections and 17 by histologic sections. The proximity of the AV
      nodal artery to the surface landmarks of the triangle of Koch was variable, but
      it was notable that in 75% of specimens the artery passed close to the
      endocardial surface of the right atrium and within 0.5 to 5 mm of the mouth of
      the coronary sinus. In all specimens, the mean distance of the artery to the
      endocardial surface was 3.5 +/- 1.5 mm at the base of Koch's triangle. The
      location of the compact AV node and its inferior extensions varied within the
      landmarks of the triangle. At the mid-level of Koch's triangle, the compact node
      was medially situated in 82% of specimens, but it was closer to the hinge of the
      tricuspid valve in the remaining 18% of specimens. In 12% of specimens, the
      inferior parts of the node extended to the level of the mouth of the coronary
      sinus. CONCLUSION: The nodal artery runs close to the orifice of the coronary
      sinus, the endocardial surface of the right atrium, the middle cardiac vein, and
      the specialized conduction tissues in most hearts. The nodal artery and/or the AV
      conduction tissues can be at risk of damage when ablative procedures are carried
      out at the base of the triangle of Koch.

PMID- 11232622
TI  - Alterations of sodium channel kinetics and gene expression in the postinfarction
      remodeled myocardium.
AB  - INTRODUCTION: After a myocardial infarction (MI), the heart undergoes a
      remodeling process that includes hypertrophy of noninfarcted left ventricular
      myocytes. Alterations in the genetic expression, including reexpression of fetal
      isogene patterns, can result in electrophysiologic changes that contribute to the
      arrhythmogenicity of post-MI heart. The present study investigated possible
      alterations in gene expression of Na+ channel subtypes, as well as the kinetics
      of the Na+ current (I(Na)), in 3- to 4-week-old post-MI rat remodeled left
      ventricular myocardium. METHODS AND RESULTS: Using a macropatch technique, we
      showed increased Na+ channel bursting activity during sustained depolarization in
      post-MI remodeled myocytes resulting in a large slow component of the I(Na)
      decay. A tetrodotoxin-sensitive current contributed 18% to the prolonged APD90 of
      isolated post-MI myocytes compared with 6% in control myocytes. Our molecular
      studies revealed that, in addition to the rat heart I (rH I) subtype, thought to
      be the predominant subtype that encodes a tetrodotoxin-resistant isoform, the
      brain subtypes NaCh I and NaCh Ia also are expressed in the rat myocytes. Post-MI
      remodeled myocardium showed increased expression of NaCh I protein with reversion
      of the NaCh Ia/NaCh I isoform ratio toward the fetal phenotype. CONCLUSION: Our
      findings raise the possibility that the increase in the slow component of I(Na)
      in post-MI remodeled myocytes is secondary to the increased expression of NaCh I.
      Additional studies are required to address these questions and to characterize
      the functional role of the NaCh I subtypes in cardiac myocytes.

PMID- 11232623
TI  - Sodium channel inactivation abnormalities associated with heart disease: ionic
      remodeling and arrhythmogenic channelopathies.

PMID- 11232624
TI  - Electrocardiographic imaging: I. Effect of torso inhomogeneities on body surface
      electrocardiographic potentials.
AB  - INTRODUCTION: Body surface potential maps (BSPMs) and conventional ECG reflect
      electrical sources generated by cardiac excitation and repolarization and
      noninvasively provide important diagnostic information about the electrical state
      of the heart. Because the heart is located within the torso volume conductor,
      body surface potentials also reflect the effects of torso inhomogeneities, which
      include blood, lungs, bone, muscle, fat, and fluid. It is necessary to
      characterize and understand these effects in order to interpret BSPM and ECG in
      terms of cardiac activity without "contamination" from the inhomogeneous volume
      conductor. METHODS AND RESULTS: Actual measured epicardial and body surface
      potentials were obtained during normal sinus rhythm and for different pacing
      protocols from a Langendorff-perfused dog heart suspended in a human-shaped torso
      tank. Accurate geometry of the torso inhomogeneities was digitized from the
      Visual Human Project and appropriately introduced into a computer model of the
      tank setup. The geometry and electrical properties of the volume conductor could
      be varied. Both homogeneous and inhomogeneous torsos have major smoothing effects
      on BSPM, which is of very low resolution compared with its corresponding
      epicardial potential pattern. Relative to a homogeneous torso, the
      inhomogeneities have only a minor effect on BSPM patterns. They augment potential
      magnitudes depending on the pattern of epicardial activation. Variations of
      geometry and electrical properties within the normal physiologic range have
      minimal effects. CONCLUSION: Effects of torso inhomogeneities on 12-lead ECGs are
      minimal, and the associated ECG changes fall within the range of normal
      interindividual variations.

PMID- 11232625
TI  - Electrocardiographic imaging: II. Effect of torso inhomogeneities on noninvasive
      reconstruction of epicardial potentials, electrograms, and isochrones.
AB  - INTRODUCTION: Noninvasive electrocardiographic imaging (ECGI) involves inverse
      reconstruction of epicardial potentials, electrograms (EGMs), and isochrones from
      body surface potential maps (BSPMs). The heart lies in a volume conductor that
      includes lungs, blood, bone, muscle, and fluid. We investigate the effects of
      these torso inhomogeneities on reconstructed epicardial potentials, EGMs, and
      isochrones to address the issue of whether they should be included in clinical
      ECGI methodology. METHODS AND RESULTS: Potential data were obtained for different
      pacing protocols from a dog heart suspended in a human-shaped torso tank.
      Accurate geometry of torso inhomogeneities was digitized from the Visual Human
      Project and appropriately introduced into a computer model of the torso. Three
      models were used: accurate inhomogeneous torso, homogeneous torso, and a torso
      with stylized lungs (to generate an approximate model). The inhomogeneous model
      was used to compute BSPMs from the measured epicardial potentials. These BSPMs
      were the starting point for inverse computations in the different torso models.
      Epicardial potential maps, EGMs, and isochrones were computed. The homogeneous
      model produced slightly less accurate epicardial potential reconstructions than
      the inhomogeneous model and stylized lung model, but epicardial potential
      patterns, EGMs, isochrones, and locations of pacing sites were reconstructed with
      comparable accuracy when torso inhomogeneities were ignored. CONCLUSION: The
      results demonstrate that, in the clinical application, it is not necessary to
      include torso inhomogeneities for noninvasive reconstructions of epicardial
      potentials, EGMs, and activation sequences.

PMID- 11232626
TI  - The forward and inverse problems: what are they, why are they important, and
      where do we stand?

PMID- 11232627
TI  - Evidence of sinoatrial block as a curative mechanism in radiofrequency current
      ablation of inappropriate sinus tachycardia.
AB  - Inappropriate sinus tachycardia is a nonparoxysmal tachycardia characterized by
      high resting heart rates and a disproportionate response to activity. Sinus node
      modification with radiofrequency current has been used successfully as treatment
      for this arrhythmia. However, the electrophysiologic mechanisms leading to
      successful modification are not yet fully elucidated. We report a case of a
      patient with drug-resistant inappropriate sinus tachycardia in whom successful
      treatment of the arrhythmia was achieved by documented sinoatrial exit block
      induced by radiofrequency current applications.

PMID- 11232628
TI  - The Brugada syndrome: ionic basis and arrhythmia mechanisms.

PMID- 11232629
TI  - Alternating bigeminy.

PMID- 11232631
TI  - The dimensions of dimension.

PMID- 11232630
TI  - Brugada syndrome mimicked by tricyclic antidepressant overdose.

PMID- 11232632
TI  - Clinical competency statement: implantation and follow-up of cardioverter
      defibrillators.

PMID- 11232633
TI  - The phytoestrogen alpha-zearalenol reverses endothelial dysfunction induced by
      oophorectomy in rats.
AB  - It has been shown recently that alpha-zearalenol, a resorcyclic acid lactone,
      prevents bone loss in a rat model of postmenopausal bone loss. We have therefore
      investigated the effects of this phytoestrogen on endothelial dysfunction induced
      by estrogen deficiency in rats. Female mature Sprague-Dawley rats underwent a
      bilateral oophorectomy (OVX rats). Sham-operated animals (sham OVX rats) were
      used as controls. Three weeks after surgery, animals were randomized to the
      following treatments: alpha-zearalenol (1 mg/kg/day, i.m., for 4 weeks), 17beta
      estradiol (20 microg/kg/day, i.m., for 4 weeks), or their vehicle (100 microl,
      i.m., of cottonseed oil). Two other groups of rats were treated with alpha
      zearalenol or 17beta-estradiol plus the pure estrogen receptor antagonist ICI
      182780 (2.5 mg/kg/day, i.m., for 4 weeks). Mean arterial blood pressure (MAP),
      heart rate (HR), total plasma cholesterol, plasma estradiol, and plasma alpha
      zearalenol were studied. We also investigated endothelial-dependent
      (acetylcholine, 10 nM to 10 microM) and endothelial-independent (sodium
      nitroprusside, 15 nM to 30 nM) relaxation of aortic rings, as well as N(G)-methyl
      L-arginine (L-NMA: 10 to 100 microM)-induced vasoconstriction and calcium
      dependent nitric oxide synthase (cNOS) activity in homogenates of lungs taken
      from both sham OVX rats and OVX rats. Untreated OVX rats had, compared with sham
      OVX animals, unchanged body weight, MAP, HR, and plasma cholesterol. In contrast
      oophorectomy reduced plasma estradiol levels (OVX, 2 +/- 0.5 pg/ml; sham OVX, 35
      +/- 6 pg/ml), impaired endothelial-dependent relaxation and blunted L-NMA-induced
      contraction (L-NMA 100 microM: sham OVX, 2.7 +/- 0.3 g/mg tissue; OVX, 1.3 +/-
      0.1 g/mg tissue). Moreover OVX rats showed a reduced calcium-dependent NO
      synthase (cNOS) activity. Treatment with alpha-zearalenol or with 17beta
      estradiol reverted the endothelial dysfunction and increased cNOS activity in
      lung homogenates. These effects were abolished by the pure estrogen receptor
      antagonist ICI 182780. Our data suggest that alpha-zearalenol improves
      endothelial-dependent relaxation in OVX rats through an estrogen receptor
      mediated effect.

PMID- 11232634
TI  - Oncostatin M production by blood and alveolar neutrophils during acute lung
      injury.
AB  - Polymorphonuclear neutrophils (PMN) are involved in the pathogenesis of acute
      lung injury (ALI), secreting numerous mediators such as proteases, reactive
      oxygen species, and cytokines. Because we had recently observed the ability of
      normal human PMN to degranulate and synthesize oncostatin M (OSM), an IL-6-family
      cytokine, we quantified OSM production ex vivo by highly purified blood and
      alveolar PMN from 24 ventilated patients with ALI, including some patients with
      severe pneumonia. Most of the patients had no detectable OSM in plasma, and OSM
      production by cultured blood PMN was similar to that of healthy controls.
      However, OSM was present in bronchoalveolar lavage (BAL) fluid supernatant, with
      significantly higher levels during pneumonia. In addition, alveolar OSM levels
      correlated with the number of PMN obtained by BAL, suggesting that PMN are an
      important source of OSM within the alveoli. Indeed, purified alveolar PMN from
      all of the patients, especially those with pneumonia, strongly produced OSM.
      Interestingly, in the latter patients, alveolar PMN always produced more OSM than
      autologous blood PMN. These results document the functional duality of PMN in ALI
      by showing the participation of PMN in the modulation of lung inflammation.

PMID- 11232635
TI  - Abnormal distribution of aquaporin-5 water channel protein in salivary glands
      from Sjogren's syndrome patients.
AB  - Patients with Sjogren's syndrome (SS) suffer from deficient secretion of saliva
      due to an autoimmune destruction of salivary glands, however, glandular
      dysfunction also occurs without destruction. Based upon its abnormal distribution
      in SS salivary glands, a potential role for the water channel protein aquaporin-5
      (AQP5) is proposed in the pathogenesis of SS. The immunohistochemical
      distribution of AQP5 was compared in minor salivary gland biopsies obtained from
      women after informed consent: primary SS (53.2 +/- 14 years old, n = 10), healthy
      volunteers (46.2 +/- 17 years old, n = 10), patients with sarcoidosis (37 and 48
      years old), and patients with non-specific sialoadenitis (54 and 61 years old).
      Biopsies from normal subjects revealed AQP5 primarily at the apical membrane of
      the salivary gland acinus. In contrast, biopsies from SS patients revealed AQP5
      primarily at the basal membranes of the acinus. The AQP5 distribution in biopsies
      from patients with other dry mouth disorders, such as non-specific sialoadenitis
      or sarcoidosis, was similar to biopsies from control subjects. Computer-assisted
      microscopy was performed to quantitatively evaluate AQP5 distribution in the
      immunoreactive acini of both SS and control subjects. Biopsies from SS patients
      had higher labeling indices (percentage of acinus area immunoreactive for AQP5)
      at the basal membrane when compared with biopsies from control subjects. In
      contrast, biopsies of SS patients exhibited lower labeling indices at the apical
      membrane when compared with biopsies from control subjects. To verify the
      specificity of the AQP5 antibody, Western blot analysis was performed on
      membranes from Xenopus oocytes injected with AQP5 cRNA or on membranes from minor
      salivary glands of control subjects and SS patients. In each case, the
      immunoblots had a 27 kd band, corresponding to the expected molecular weight of
      AQP5. Abnormal distribution of AQP5 in salivary gland acini is likely to
      contribute to the deficiency of fluid secretion, which is a defining feature of
      Sjogren's syndrome.

PMID- 11232636
TI  - Relocalization of cathepsin D and cytochrome c early in apoptosis revealed by
      immunoelectron microscopy.
AB  - Cathepsin D was translocated from lysosomal structures to the cytosol in primary
      cultures of neonatal rat cardiomyocytes exposed to oxidative stress, and these
      cells underwent apoptotic death during subsequent incubation. Temporal aspects of
      cathepsin D relocalization, cytochrome c release, and decrease in mitochondrial
      transmembrane potential (delta psi(m)) were studied in myocytes exposed to the
      redox-cycling xenobiotic naphthazarin (5,8-dihydroxy-1,4-naphthoquinone).
      Immunofluorescence labeling revealed that cathepsin D was translocated to the
      cytosol after 30 minutes of naphthazarin treatment, and cytochrome c was released
      from mitochondria to the cytosol after 2 hours. Western blotting and
      immunoelectron microscopy indicated a minor release of cytochrome c after only 30
      minutes and 1 hour, respectively. Thereafter, a decrease in delta psi(m) was
      detected using the delta psi(m)sensitive dye JC-1 and confocal microscopy, and
      ultrastructural analysis indicated apoptotic morphology. Pretreatment of the
      cultures with the cathepsin D inhibitor pepstatin A prevented release of
      cytochrome c from mitochondria and maintained the delta psi(m). Moreover,
      ultrastructural examination showed no apoptotic morphology. These findings
      suggest that lysosomal destabilization (detected as the release of cathepsin D)
      and release of cytochrome c from mitochondria take place early in apoptosis.
      Also, the former event probably occurs before the latter during apoptosis induced
      by oxidative stress because pretreatment with pepstatin A prevented release of
      cytochrome c and loss of delta psi(m) in cardiomyocytes exposed to naphthazarin.

PMID- 11232637
TI  - Clinical relevance of T1-S, an oncogene-inducible, secreted glycoprotein of the
      immunoglobulin superfamily, in node-negative breast cancer.
AB  - Axillary lymph node-negative breast cancer patients have a low risk for disease
      recurrence, and the majority of these patients are cured by surgery alone.
      However, accurate identification of that 30% of node-negative patients who are at
      high-risk for relapse and who might therefore benefit from adjuvant systemic
      therapy has not been possible using traditional histomorphological and clinical
      prognostic factors alone. Identification of novel tumor-associated molecules may
      therefore provide a basis for a better understanding of and eventually for an
      interference with disease progression. We have recently reported on tumor
      associated RNA up-regulation of the secreted, soluble T1-S receptor in node
      negative breast cancer. In the present study we analyzed the tumor-associated
      level of the T1-S receptor using semiquantitative immunohistochemistry in a
      collective of 102 node-negative breast carcinomas to study its clinical
      relevance. A high T1-S immunoreactivity score indicating T1-S overexpression was
      observed in 58 of 102 (57%) cases. The T1-S score was independent of the tumor
      size, type, grade, steroid hormone receptor status, and the proliferation rate
      determined by monoclonal antibody against KI-67 protein (MIB1)
      immunohistochemistry. In univariate and multivariate analysis of disease-free
      survival, a high T1-S score (p = 0.003) and a low MIB1 score (p = 0.001) were the
      only parameters that were highly significantly associated with an improved
      disease-free survival period. We conclude that T1-S receptor overexpression is a
      novel and independent tumor biological factor that may be associated with reduced
      progression of lymph node-negative breast cancer.

PMID- 11232638
TI  - Down-Regulation of MT1-MMP expression by the alpha3 chain of type IV collagen
      inhibits bronchial tumor cell line invasion.
AB  - The basement membrane (BM) is the first barrier encountered by tumor cells when
      they become invasive. Moreover, some invasive tumor clusters are surrounded by a
      remnant or neosynthetized BM material. We have previously reported the presence
      of a particular alpha chain of type IV collagen, the alpha3(IV) chain, in
      bronchopulmonary carcinomas. This chain was not detected in the normal bronchial
      epithelium, but was found around some invasive tumor cluster BM. In the present
      study, we examined the effects of the alpha3(IV) chain on the invasive properties
      of bronchial tumor cell lines, with special emphasis on their expression of
      matrix metalloproteinase-2 (MMP-2) and its activator, membrane type 1-matrix
      metalloproteinase (MT1-MMP), which is largely involved in tumor progression. Two
      epithelial bronchial cell lines (16HBE14o- and BZR), showing different invasive
      abilities, were evaluated. Using the Boyden chamber invasion assay, we
      demonstrated that the alpha3(IV) chain inhibits the invasive properties of BZR
      cells and modifies their morphology by inducing an epithelial cell shape. In the
      presence of the recombinant NC1 domain of the alpha3(IV) chain, the expression of
      MMP-2 and tissue inhibitor of metalloproteinase-2 (TIMP-2) was not modified in
      either cell line. The NC1 alpha3(IV) domain did not modulate the MT1-MMP
      expression of noninvasive 16HBE14o- cells, whereas a 50% decrease of MT1-MMP mRNA
      was observed in invasive BZR cells. Accordingly, Western blot analyses showed a
      disappearance of the 45-kd MT1-MMP form when BZR cells were treated with the
      recombinant NC1 alpha3(IV) domain. These findings suggest that the alpha3 chain
      of type IV collagen may play a role in tumor invasion, at least by decreasing the
      expression and synthesis of MT1-MMP.

PMID- 11232640
TI  - Response to X-irradiation of Fanconi anemia homozygous and heterozygous cells
      assessed by the single-cell gel electrophoresis (comet) assay.
AB  - Fanconi anemia (FA) is an autosomal recessive disorder characterized by bone
      marrow failure and cancer susceptibility. Patient cells are sensitive to a
      variety of clastogens, most prominently cross-linking agents. Although there is
      the long-standing clinical impression of radiosensitivity, in vitro studies have
      yielded conflicting results. We exposed peripheral blood mononuclear cells from
      FA patients and carriers to x-rays and determined their DNA damage and repair
      profiles using the alkaline single-cell gel electrophoresis (comet) assay.
      Studies were carried out in two independent series of experiments by two
      laboratories using different protocols. The cells of both FA patients and
      carriers showed uniformly high initial DNA damage rates as assessed by the total
      initial tail moment. In addition, the average residual tail moment at 30 to 50
      minutes and the repair half-time parameters were significantly elevated. These
      findings suggest an increased release of fragmented DNA following x-ray exposure
      in cells that carry one or two mutations in one of the FA genes. The comet assay
      may be a useful adjunct for heterozygote detection in families of FA patients.

PMID- 11232639
TI  - Hypoxia stimulates release of the soluble form of fas ligand that inhibits
      endothelial cell apoptosis.
AB  - Fas ligand (FasL), an apoptosis-inducing cytokine, is constitutively expressed on
      endothelial cells (EC). Here, we report that the soluble form of FasL (sFasL) is
      released from EC and inhibits hypoxia-induced EC apoptosis. For hypoxia
      experiments, human EC were exposed to low oxygen tension in airtight chambers
      flushed with preanalyzed gas mixtures (1% oxygen, 5% CO2, 94% N2) at 37 degrees
      C. Exposure of cultured EC to hypoxia transiently increased FasL mRNA and protein
      levels. The maximum increase was observed at 3 and 6 hours after exposure to
      hypoxia, respectively. Although sFasL protein was not detected in the supernatant
      from EC without hypoxia, sFasL protein level in the supernatant was transiently
      increased from 6 hours and disappeared again at 24 hours after the exposure to
      hypoxia. Interestingly, the supernatant from hypoxia-exposed EC inhibited EC
      apoptosis induced by hypoxia, which was abolished by a neutralizing antibody
      against FasL. In addition, incubation with KB8301, an inhibitor of
      metalloproteinase, suppressed the release of sFasL from EC and enhanced hypoxia
      induced apoptosis in EC. Furthermore, exogenously added recombinant sFasL
      inhibited hypoxia-induced apoptosis. These findings indicate that sFasL released
      from EC may inhibit hypoxia-induced EC apoptosis. Therefore, the shedding of FasL
      could be a new therapeutic target in regulating hypoxia-induced EC injury.

PMID- 11232641
TI  - Centrilobular endothelial cell injury by diquat in the selenium-deficient rat
      liver.
AB  - Low doses of diquat cause massive liver necrosis and death of selenium-deficient
      rats within a few hours. Protection against this injury by selenium correlates
      with the presence of selenoprotein P, an extracellular selenoprotein that
      associates with endothelial cells. Selenium-deficient rats were injected with
      diquat (10 mg/kg) and their livers were removed for light and electron microscopy
      at times up to 120 minutes after injection. Selenium-replete animals were studied
      before and 120 minutes after the same dose of diquat. With selenium deficiency,
      diquat caused injury to centrilobular endothelial cells. This injury was evident
      20 minutes after diquat injection and progressed to cell loss at 60 minutes after
      diquat injection. At 120 minutes, endothelial cells were virtually absent from
      the centrilobular regions and hepatocytes in those areas were undergoing
      necrosis. Portal and midzonal areas remained normal in selenium-deficient livers,
      as did the entire liver lobule of selenium-replete rats. These findings indicate
      that the initial liver lesion in selenium-deficient rats given diquat is injury
      of the endothelial cells in the centrilobular region. After detachment of the
      endothelial cells, centrilobular hepatocytes undergo necrosis. We postulate that
      selenoprotein P protects the centrilobular endothelial cells against injury by
      oxidant molecules that result from diquat administration.

PMID- 11232642
TI  - Truncated DCC reduces N-cadherin/catenin expression and calcium-dependent cell
      adhesion in neuroblastoma cells.
AB  - The deleted in colorectal cancer (DCC) protein is important in the pathway
      guidance of cells and cell processes during neural development, and DCC has also
      been implicated in the aberrant cellular migrations of neuroblastoma
      dissemination. We attempted to further define DCC protein function by the
      overexpression of full-length and truncated DCC constructs in a human
      neuroblastoma cell line. Overexpression of the truncated DCC protein resulted in
      a less epithelioid morphology. This was accompanied by decreases in expression of
      N-cadherin and alpha- and beta-catenin by immunoblot and Northern blot analysis.
      Levels of desmoglein were relatively less affected, whereas endogenous DCC
      protein levels were increased in the truncated transfectants. N-cadherin
      immunofluorescence was consistent with the immunoblot studies and localized the
      protein to the cytoplasm and sites of cell-cell contact. Cell aggregation studies
      demonstrated diminished calcium-dependent aggregation in the truncated
      transfectants. In conclusion, overexpression of a truncated DCC protein in
      neuroblastoma cells resulted in the loss of an epithelioid morphology, diminished
      expression of N-cadherin and alpha- and beta-catenin, and diminished calcium
      dependent cell adhesion. These studies provide the first evidence of an apparent
      functional link between DCC and N-cadherin/catenin-dependent cell adhesion.

PMID- 11232643
TI  - Leiomyosarcomas and most malignant fibrous histiocytomas share very similar
      comparative genomic hybridization imbalances: an analysis of a series of 27
      leiomyosarcomas.
AB  - Twenty-seven tumor samples with a diagnosis of leiomyosarcomas (LMS) were
      characterized by comparative genomic hybridization. The results were compared
      with immunohistochemical analysis of the smooth muscle profile of the tumors and
      expression of the RB1 gene protein. The comparative genomic hybridization
      profiles suggested that 7 of the 27 tumors might have been misclassified. High
      levels of DNA amplification were detected in 20 different small regions and
      recurrently involved bands 1p34, q21, 12q13-15, 17p, and 22q. Most recurrent
      simple gains were noted at sites such as 1p3, 1q21, 15q12-15, 16p, 17p and 17q,
      19, 20q, 22q, and Xp. Significant losses of chromosome 13 were detected in 19 of
      the 27 tumors with a putative common region of loss in bands 13q14-21. Losses of
      chromosomes 1q, 2p and 2q, 4q, 9p, 10p and 10q, 11p and 11q23, and 16q were also
      highly recurrent. A comparative analysis between the most frequent genomic
      imbalances observed in this study of LMS and the genomic imbalances observed in a
      large proportion of malignant fibrous histiocytomas (MFH) from a previous study
      demonstrated that both types of tumors had similar recurrent imbalances. Although
      MFH were once thought to be a separate member of the soft tissue sarcoma family,
      our observations support the hypothesis that MFH are a morphologic modulation in
      the tumoral progression of other sarcomas, particularly LMS.

PMID- 11232644
TI  - Methylation silencing and mutations of the p14ARF and p16INK4a genes in colon
      cancer.
AB  - The INK4a-ARF locus encodes two tumor suppressor proteins involved in cell-cycle
      regulation, p16INK4a and p14ARF, whose functions are inactivated in many human
      cancers. The aim of this study was to evaluate p14ARF and p16INK4a gene
      inactivation and its association with some clinocopathological parameters in
      colon cancer. The mutational and methylation status of the p14ARF and p16INK4a
      genes was analyzed in 60 primary colon carcinomas and 8 colon cancer cell lines.
      We have identified the first two reported mutations affecting exon 1beta of
      p14ARF in the HCT116 cell line and in one of the primary colon carcinomas. Both
      mutations occur within the N-terminal region of p14ARF, documented as important
      for nucleolar localization and interaction with Mdm2. Tumor-specific methylation
      of the p14ARF and p16INK4a genes was found in 33% and 32% of primary colon
      carcinomas, respectively. Methylation of the p14ARF was inversely correlated with
      p53 overexpression (p = 0.02). p14ARF and p16INK4a gene methylation was
      significantly more frequent in right-sided than in left-sided tumors (p = 0.02).
      Methylation of the p14ARF gene occurred more frequently in well-differentiated
      adenocarcinomas (p = 0.005), whereas the p16INK4a gene was more often methylated
      in poorly differentiated adenocarcinomas (p = 0.002). The present results
      underline the role of p14ARF and p16INK4a gene inactivation in the development of
      colon carcinoma. They suggest that the methylation profile of specific genes, in
      particular p14ARF and p16INK4a, might be related to biologically distinct subsets
      of colon carcinomas and possibly to different tumorigenic pathways.

PMID- 11232645
TI  - Sex steroids influence pancreatic islet hypertrophy and subsequent autoimmune
      infiltration in nonobese diabetic (NOD) and NODscid mice.
AB  - Female nonobese diabetic (NOD) mice more frequently develop autoimmune diabetes
      than NOD males. Orchidectomy of the latter aggravates insulitis and diabetes.
      Because clear differences in immune function have not been observed between
      prediabetic females and males, before or after castration, we hypothesized that
      sex-related differences in diabetes incidence are related to target organ
      specific actions of sex steroids. Previously, we showed that prediabetic NOD
      females develop hyperinsulinemia and subsequently mega-islets. Infiltration of
      the first inflammatory leukocytes is predominantly associated with these mega
      islets. Here, we determined the relationship between sex hormones, mega-islet
      formation, and infiltrating cells in NOD and nonobese diabetic/severe combined
      immune-deficient (NODscid) mice. Mega-islet formation was reduced in NOD males
      compared with NOD females, and orchidectomy increased it, indicating a
      relationship between androgen levels and mega-islet formation. Moreover, enhanced
      mega-islet formation in castrated NOD males was associated with increased numbers
      of infiltrating leukocytes. Castrated NODscid males also exhibited increased mega
      islet formation and dendritic cell infiltration, indicating that lymphocytes are
      not required for castration-induced effects. In conclusion, we show that
      androgens influence pancreatic islets and autoimmune infiltration in NOD and
      NODscid mice. This suggests that the gender difference in diabetes incidence in
      NOD mice is related to target organ-specific androgen effects.

PMID- 11232646
TI  - Molecular alterations of Barrett's esophagus on microdissected endoscopic
      biopsies.
AB  - Alterations in proto-oncogenes and tumor suppressor genes play a role in the
      sequence from Barrett's metaplasia to esophageal adenocarcinoma. The present
      study aims to ascertain whether molecular abnormalities take place in Barrett's
      metaplasia and low-grade dysplasia and to correlate them with the histological
      features of the esophageal mucosa. Forty-one formalin-fixed, paraffin-embedded
      endoscopic esophageal biopsies were classified according to the type of
      metaplastic changes (noncolumnar fundic and cardial metaplasia; columnar
      metaplasia, with and without intestinal features). After microdissection samples
      were examined for loss of heterozygosity (LOH) using polymorphic markers on 5q
      (D5S82), corresponding to APC (adenomatous polyposis coli) gene, 13q (CA repeat
      in intron 2 position 14815 to 14998 of the retinoblastoma gene), 17p (D17S513)
      corresponding to p53 locus, and for p53 mutations. Molecular alterations
      including LOH, allelic imbalance, and microsatellite instability could be
      detected in all types of metaplastic changes and sporadically in the squamous
      epithelium adjacent to the metaplastic tissue. Molecular alterations involving
      microsatellites D5S82 and the CA repeat inside the retinoblastoma gene were more
      frequent in nonintestinal metaplasia whereas those involving the p53 locus took
      place in columnar intestinal metaplasia and in low-grade dysplasia. Clonal
      changes were demonstrated in different metaplastic areas in three patients.
      Genetic alterations comprising LOH and microsatellite instability characterize
      Barrett's mucosa and appear related to the type of metaplastic change. Some of
      them precede the development of intestinal metaplasia, suggesting that genetic
      alterations take place earlier than previously thought.

PMID- 11232647
TI  - Effect of articular step-off and meniscectomy on joint alignment and contact
      pressures for fractures of the lateral tibial plateau.
AB  - OBJECTIVES: To determine the effects of intraarticular step-off and lateral
      meniscectomy on the alignment of the articular axis, contact area, and pressures
      for lateral tibial plateau fractures. DESIGN: Biomechanical cadaver study.
      INTERVENTION: Six fresh cadaveric knees were used. A simulated split fracture of
      the lateral tibial plateau was reproducibly created by osteotomies, and articular
      step-offs of zero, one, two, four, and six millimeters were achieved by using
      support shims. The knee was loaded with 500 newtons in 0 degrees and 350 newtons
      in 30 degrees of flexion. A digital camera determined changes in the alignment of
      the articular axis, and F-Scan sensors were inserted into the medial and lateral
      joint compartments to determine the pressures and pressure distributions. MAIN
      OUTCOME MEASUREMENT: Each specimen was tested at step-offs of zero, one, two,
      four, and six millimeters, with the presence or absence of the lateral meniscus.
      The changes in alignment of the articular axis, the contact area, and the average
      and maximum contact pressures for each condyle were obtained. RESULTS: Increased
      articular step-off heights progressively increased valgus angulation and average
      and maximum contact pressures and progressively decreased contact areas in
      lateral compartment. At a six-millimeter step-off with 0 degrees of flexion, the
      valgus angle increased an average of 7.6 degrees, and average contact pressures
      and maximum contact pressures increased an average of 208 percent and 97 percent,
      respectively, and contact area decreased an average of 33 percent (p < 0.05).
      Meniscectomy increased valgus angles by an average of 38 percent and contact
      pressures by an average of 45 percent and decreased contact areas by 26 percent
      in the lateral compartment at the same articular step-off heights (p < 0.05).
      CONCLUSION: The results of this study show the importance of decreasing articular
      step-off heights in treating lateral tibial plateau split fractures, particularly
      if a meniscectomy is performed.

PMID- 11232648
TI  - Mechanical behavior of the Lisfranc and dorsal cuneometatarsal ligaments: in
      vitro biomechanical study.
AB  - OBJECTIVES: To define the anatomy and mechanical properties of two ligaments
      stabilizing the medial tarsometatarsal joints: the Lisfranc ligament and the
      dorsal cuneometatarsal ligament. DESIGN: Cadaveric study in normal feet. SETTING:
      Biomechanics laboratory. PATIENTS OR PARTICIPANTS: Twelve fresh-frozen cadaveric
      feet were studied. INTERVENTION: The Lisfranc and dorsal cuneometatarsal
      ligaments were dissected, dimensions measured, and material properties determined
      with a servohydraulic MTS machine on bone-ligament-bone preparations. MAIN
      OUTCOME MEASUREMENTS: Stiffness, strain, stress, modulus, failure load, ligament
      length, width, thickness, and cross-sectional area were determined. RESULTS:
      Dorsal ligament stiffness was 66.3+/-18.3 newtons per millimeter and the Lisfranc
      ligament stiffness was 189.7+/-57.2 newtons per millimeter. The failure load of
      the dorsal ligament averaged 150.7+/-33.1 newtons and for the Lisfranc ligament,
      368.8+/-126.8 newtons. CONCLUSIONS: The stiffness and load to failure of the
      dorsal cuneometatarsal ligament were much higher than anticipated, which
      indicates that it contributes significantly to stabilizing the second metatarsal
      to the first cuneiform.

PMID- 11232650
TI  - Lag screw only fixation of the lateral malleolus.
AB  - OBJECTIVES: To evaluate the use of lag screw only fixation of noncomminuted
      oblique fractures of the lateral malleolus in patients younger than fifty years
      of age. DESIGN: Prospective evaluation. SETTING: Level I trauma center. PATIENTS
      AND PARTICIPANTS: Forty-seven ankle fractures with simple oblique patterns and no
      comminution that were long enough to accept two lag screws placed at least 1
      centimeter apart were prospectively evaluated. All patients were younger than
      fifty years of age. There were twenty-three ligamentous SE4, eighteen bimalleolar
      SE4, and six PE4 fractures. INTERVENTION: Open reduction and internal fixation
      with lag screw only fixation of the lateral malleolus. MAIN OUTCOME MEASUREMENTS:
      Radiographic and clinical outcome parameters were compared with those of a cohort
      of patients previously treated at the same institutions using different
      techniques. RESULTS: Thirty-five patients' ankles were fixed with two lag screws,
      ten with three lag screws, and two with four lag screws. The incision for lag
      screw placement was 30 percent shorter and slightly more anterior than that in
      the comparison group. No patient lost reduction and there were no soft-tissue
      complications in the group. Follow up averaged 1.6 years for forty-two patients.
      One patient (2 percent) had complaints of lateral pain in the study, compared
      with 17 percent in the plate group. No patient fixed with lag screws had palpable
      hardware, as compared with 56 percent in the plate group. None had any
      restrictions in shoe wear, as compared with 15 percent in the plate group. No
      patient required screw removal, as compared with 31 percent in the plate group.
      There was no difference in radiographic outcome between the two groups.
      CONCLUSIONS: Lag screw only fixation is a useful and successful method for
      appropriately selected lateral malleolar fractures.

PMID- 11232649
TI  - Open fractures of the forearm in children.
AB  - OBJECTIVE: To describe the epidemiology, early results of treatment, and
      complications associated with open fractures of the forearm in children. DESIGN:
      Retrospective review of patients treated according to protocol. SETTING: Level I
      trauma center. PATIENTS/PARTICIPANTS: All children with an open fracture of the
      forearm during a four-year period (n = 76). Fourteen patients were excluded
      because of inadequate follow-up or incomplete medical records. INTERVENTION: All
      fractures were treated with irrigation and debridement, and parenteral
      antibiotics. Twenty-five patients were managed with cast immobilization only, and
      the remaining thirty-seven, with internal fixation either with transcutaneous
      pins, intramedullary pins, or plates and screws, followed by immobilization in a
      cast. MAIN OUTCOME MEASUREMENTS: Time to union, angular alignment at union, and
      incidence of complications. RESULTS: The average time to union was 8.9 weeks
      (median, eight weeks; range, 6 to 17 weeks). There were no nonunions, but three
      of the sixty-two fractures had delayed union. Eight of the sixty-two fractures
      healed with an angular deformity of more than 10 degrees, and two developed
      infections, one deep and one superficial. There were three preoperative and four
      postoperative nerve palsies, which all resolved spontaneously. CONCLUSIONS: Open
      fractures of the forearm in children, treated with prompt administration of
      parenteral antibiotics followed by debridement, were associated with a fairly low
      incidence of complications. Although we found that the use of some form of
      internal fixation tended to reduce both the need to remanipulate these fractures
      (p = 0.08), and to minimize the incidence of angular deformity greater than 10
      degrees (p = 0.16), these findings did not reach statistical significance.

PMID- 11232651
TI  - Novel computer-assisted fluoroscopy system for intraoperative guidance:
      feasibility study for distal locking of femoral nails.
AB  - OBJECTIVES: Orthopaedic procedures that use fluoroscopy require intraoperative
      mental navigation of the surgical tools in a three-dimensional space. Moreover,
      because of their reliance on real-time monitoring, such procedures are frequently
      associated with increased x-ray exposure. The goal of this study was to develop a
      computer-guided surgical navigation system based on fluoroscopic images that not
      only facilitates direction of surgical tools within anatomy, but also provides
      constant feedback without the need for radiologic updates. To evaluate the
      feasibility of the new technology, the authors used it on cases requiring distal
      locking of femoral nails. METHODS: The hardware components of the system include
      an instrumented C-arm, optoelectronic position sensor, stereotactic tools, and
      custom-made software. Computer integration of these devices permitted C-arm
      alignment assistance and real-time navigation control without constant x-ray
      exposure. The nails were locked in a variety of media, including plastic femurs,
      dry human femoral specimens, human cadavers, and one clinical case. Unreamed
      femoral nail sizes ranged from 9/340 to 12/400. Radiographs were taken to confirm
      that screws were positioned correctly, and fluoroscopic time associated with the
      locking procedure was recorded. RESULTS: All distal holes were locked
      successfully. In eight (11 percent) of seventy-six holes, the drill bit touched
      the canal of the locking hole, albeit with no damage to the nail and no clinical
      consequences. The fluoroscopy time per pair of screws was 1.67 seconds.
      CONCLUSIONS: The developed system enables the physician to precisely navigate
      surgical instruments throughout the anatomy using just a few computer-calibrated
      radiographic images. The total radiation time per procedure can be significantly
      reduced because additional x-ray exposure is not required for tool navigation.

PMID- 11232652
TI  - Technique for removal of broken interlocking screws.
AB  - Breakage of an interlocking screw is a known complication in tibial fractures
      treated by intramedullary nailing. This happens most often in delayed union or
      nonunion because of the lack of progressive load transference from the nail to
      the healing bone. To treat this problem, the nail and screws need to be removed.
      This article describes a simple technique for the removal of broken interlocking
      screws.

PMID- 11232653
TI  - Easily removed drill guide for pin insertion during external fixation.
AB  - A new guide for tissue protection while drilling and inserting screws in external
      fixation without taking down the system is presented. It can be used for pin
      insertion in both unilateral and ring-type external fixators. The external
      fixator is used as a template guide, and pin insertion can be easily performed
      with the fixator in place. With its use, operative time is decreased, and tissue
      protection is achieved for all pin insertions in any part of the musculoskeletal
      system.

PMID- 11232654
TI  - Traumatic unilateral avulsion of the anterior superior and inferior iliac spines
      with anterior dislocation of the hip: a case report.
AB  - A sixteen-year-old boy involved in a high-speed motor vehicle accident sustained
      an anterior hip dislocation and avulsion of the anterior ilium extending from the
      anterior superior iliac spine to the anterior inferior iliac spine. The hip was
      emergently reduced, and further imaging was obtained to evaluate the bony injury.
      Computed tomography confirmed the presence of a large displaced bony fragment
      representing avulsion of the anterior superior and inferior iliac spines and a
      smaller fragment from the reflected head of the rectus femoris. The patient
      underwent open reduction and internal fixation of the ilium two days after the
      initial injury. Postoperatively, he was allowed to bear weight as tolerated with
      crutches but to avoid active hip flexion. He went on to an uneventful recovery,
      and at last report (approximately six months after injury), he had returned to
      full activity. An extensive review of the literature failed to show a similar
      injury of ipsilateral avulsion of the anterior superior and inferior iliac spines
      and reflected head of the rectus femoris.

PMID- 11232655
TI  - Arterial injury during retrograde femoral nailing: a case report of injury to a
      branch of the profunda femoris artery.
AB  - The management of femoral shaft fractures by retrograde intramedullary nailing is
      becoming more widespread. There have been no reported intraoperative
      neurovascular injuries to the surrounding anatomy using the retrograde femoral
      nailing technique. We report a case of injury to a branch of the profunda femoris
      artery during placement of the anteroposterior proximal locking screw.

PMID- 11232656
TI  - Isolated dislocation of the second metacarpal at both ends.
AB  - A dislocation of the second metacarpal at both ends is reported herein for the
      first time. Six weeks after injuring her right hand in a fall while climbing
      stairs, a 34-year-old woman visited our clinic with pain, swelling, and deformity
      of her hand. The radiographs showed a volar dislocation of the head and a dorsal
      dislocation of the base of the second metacarpal. The probable mechanism of
      injury was the hyperextension at the metacarpophalangeal joint; this force
      dislocated the metacarpal head toward the volar plate. Force then further
      continued along the second metacarpal shaft in the hyperflexed wrist, thus
      dislocating the base dorsally. We performed an open reduction and K-wire fixation
      of the second metacarpophalangeal joint and an arthrodesis of the second
      carpometacarpal joint. At the six-month follow-up, the patient had restricted
      flexion (0 to 50 degrees) at the second metacarpophalangeal joint, but full range
      of motion at the interphalangeal joints. The grip strength on the right side was
      70% of that measured in the uninvolved hand. Key Words: Dislocation, Second
      metacarpal.

PMID- 11232657
TI  - Proximal humerus fracture.
AB  - A thirty-five-year-old man who fell from a tree is admitted to the emergency
      department with the x-rays shown below. Physical examination reveals that the
      patient is neurologically intact and has good pulses. Management of this case is
      described in the following opinions.

PMID- 11232658
TI  - Efficacy of preoperative skin traction in hip fracture patients: a prospective,
      randomized study.
AB  - OBJECTIVE: To compare the analgesic benefit of preoperative skin traction with
      the placement of a pillow under the injured extremity in patients with hip
      fractures. DESIGN: Prospective, randomized clinical study. SETTING: University
      affiliated teaching institution. PATIENTS AND PARTICIPANTS: One hundred
      consecutive patients with hip fractures admitted to the authors' institution who
      met inclusion criteria were enrolled. Fifty-five patients had femoral neck
      fractures, and forty-five patients had intertrochanteric fractures. The average
      patient age was seventy-eight years. INTERVENTION: All patients were
      preoperatively randomized into two intervention groups. One group underwent
      placement of five pounds of skin traction on the injured extremity, whereas the
      second underwent placement of a pillow under the injured extremity. Fifty
      patients were enrolled in each intervention group. RESULTS: With respect to
      immediate postintervention pain levels, patients treated with a pillow showed a
      trend toward better pain relief, as compared with patients treated with skin
      traction; however, this was not statistically significant. On the morning after
      admission, patients treated with a pillow had a statistically significant greater
      reduction in pain (p = 0.04). These patients also requested a statistically
      significant lower amount of pain medication (p < 0.01). CONCLUSIONS: The authors
      think that preoperative skin traction in patients with hip fractures does not
      provide significant pain relief, as compared with pillow placement under the
      injured extremity, and thus should not be routinely performed in this patient
      population for analgesia.

PMID- 11232659
TI  - Cutaneous metal sensitivity in patients with orthopaedic injuries.
AB  - BACKGROUND: Manufactures of orthopaedic fracture implants have turned to titanium
      in a pure form and an alloy during the past ten to fifteen years. Although
      primarily because of the biomechanical properties of this metal, concern for
      allergy to nickel and chromium ions in stainless steel was a factor in these
      decisions. OBJECTIVES: To document the incidence of baseline sensitivity to metal
      ions and the incidence of conversion to sensitivity to one of three ions in
      stainless steel in a population of trauma patients at a Level I trauma center.
      DESIGN: Prospective, consecutive patient series. SETTING: Level I trauma center.
      PATIENTS: Patients eighteen years of age and older with no history of metallic
      implants were recruited for this study between October 1995 and July 1997. Four
      hundred ninety-three patients had a Finn chamber device with chromium, nickel,
      and cobalt ions, which were read using a photographic scale on day three. Two
      hundred forty-two of these patients had placement of a second patch, at a mean
      interval of 187 days (range 45 to 589 days). INTERVENTION: Internal fixation of
      fracture or osteotomy with metal implant. MAIN OUTCOME MANAGEMENT: Cutaneous
      reactivity to metal ions. RESULTS: Prevalence of sensitivity to chromium was 0.2
      percent, to nickel 1.3 percent, and to cobalt 1.8 percent. Rates for conversion
      from a negative to positive status were 2.7 percent for chromium, 3.8 percent for
      nickel, and 3.8 percent for cobalt. Rates for desensitization (i.e., converting
      from a positive to negative status) were 2.1 percent for nickel and 3.8 percent
      for cobalt. CONCLUSION: The prevalence of sensitivity to nickel, cobalt, and
      chromium is apparently low. Similarly, internal fixation devices composed of
      stainless steel appear to result in an equal incidence of conversion to metal
      ionic sensitivity and desensitization to metal ions. It is conceivable that
      cutaneous sensitivity is not representative of deep immune response.

PMID- 11232660
TI  - Angular malalignment after intramedullary nailing of femoral shaft fractures.
AB  - OBJECTIVES: To determine factors associated with angular malalignment of femoral
      shaft fractures treated with intramedullary nails and to determine differences in
      the incidence of angular malalignment based on fracture location, fracture
      comminution, and method of treatment (i.e., antegrade or retrograde). DESIGN:
      Retrospective. SETTING: Level I trauma center. PATIENTS: Three hundred sixty
      patients with 374 femoral shaft fractures were identified from a prospectively
      obtained orthopaedic trauma database. Complete sets of immediate postoperative
      anteroposterior and lateral radiographs were available for 355 (95 percent) of
      the 374 fractures. INTERVENTION: Patients were treated with antegrade (183 cases)
      or retrograde (174 cases) intramedullary femoral nailing. MAIN OUTCOME MEASURE:
      Goniometric measurements were made on all immediate postoperative radiographs to
      determine the coronal plane and sagittal plane angular alignments. A multiple
      linear regression statistical analysis was used to determine factors associated
      with increasing angular malalignment. The incidence of malalignment was
      determined using more than 5 degrees of deformity in any plane as the definition
      of malalignment. RESULTS: Proximal fracture location, distal fracture location,
      and unstable fracture pattern were associated with increasing fracture angulation
      (p < 0.001). Fracture location in the middle third, stable fracture pattern,
      method of treatment (i.e., antegrade or retrograde), and nail diameter were not
      associated with increasing fracture angulation (p > 0.05). The incidence of
      malalignment was 9 percent for the entire group of patients, 30 percent when the
      fracture was of the proximal third of the femoral shaft, 2 percent when the
      fracture was of the middle third, and 10 percent when the fracture was of the
      distal third. The incidence of malreduction was 7 percent for patients with
      stable fracture patterns and 12 percent for those with unstable fracture
      patterns. CONCLUSIONS: Patients with fractures of the proximal third of the
      femoral shaft treated with intramedullary nails are at highest risk for
      malalignment. Proximal fracture location, distal fracture location, and unstable
      fracture pattern are associated with increasing fracture angulation.

PMID- 11232661
TI  - Mechanical comparison of endosteal substitution and lateral plate fixation in
      supracondylar fractures of the femur.
AB  - OBJECTIVE: To assess for improved rigidity with the addition of a medial
      endosteal plate to laterally plated supracondylar femoral fractures. DESIGN: A
      randomized paired study in a supracondylar femoral fracture model comparing two
      fixation methods tested cyclically in axial and torsional loading. METHODS: One
      centimeter supracondylar gap osteotomies were created in twenty synthetic femurs
      approximately six centimeters proximal to the knee joint. Ten were stabilized
      with a lateral eight-hole buttress plate alone, and ten were secured by a similar
      lateral buttress plate plus a medial endosteal eight-hole dynamic compression
      plate. Group 1 (n = 5; lateral plate alone) and Group 2 (n = 5; lateral and
      endosteal plates) were axially loaded up to 700 newtons through a materials test
      system for three cycles. A displacement transducer detected movement at the
      medial fracture gap. Group 3 (n = 5; lateral plate alone) and Group 4 (n = 5;
      lateral and endosteal plates) were tested in torsion. A rod-and-pulley system
      created an external rotation torque up to twenty Newton-meters for three cycles.
      A rotary potentiometer measured angular displacement. RESULTS: Lateral buttress
      plating with endosteal substitution showed statistically significant decreased
      motion at the fracture site in torsional (p < 0.004) and axial loading (p <
      0.0001) versus lateral buttress plating alone using Student's t test. CONCLUSION:
      The addition of a 4.5-millimeter endosteal plate to a lateral buttress plate
      provides significantly increased stability, as compared with lateral plating
      alone in a femoral supracondylar fracture model during simulated axial and
      torsional loading. Neither fixation construct, however, restored the torsional
      stability of the distal femur to its preinjury (intact) level.

PMID- 11232662
TI  - Magnetic resonance spectroscopy: a new test for differentiating ulcerative
      colitis from Crohn's disease?

PMID- 11232663
TI  - Focal neurological signs in cirrhotic patients with episodes of hepatic
      encephalopathy.

PMID- 11232664
TI  - Insulin resistance and nonalcoholic steatohepatitis: fat or fiction?

PMID- 11232665
TI  - Patients' attitudes and apprehensions about endoscopy: how to calm troubled
      waters.

PMID- 11232666
TI  - Quality of life measurement in gastroenterology: what is available?
AB  - Monitoring and enhancement of a patient's health-related quality of life (HRQL)
      is an important element of research and medical care. In a previous article, we
      provided an overview of HRQL measurement. Now we will review the structure and
      properties of the most commonly used generic and digestive disease-specific HRQL
      instruments and illustrates their use in the gastroenterology and hepatology
      literature. Generic measures have been used to study specific diseases as well as
      to compare HRQL in GI and nongastrointestinal disease. Disease specific
      instruments have been developed for inflammatory bowel disease, irritable bowel
      syndrome, dyspepsia, gastroesophageal reflux disease, liver disease, and GI
      malignancy. Further work is needed to compare disease-specific instruments and to
      define the most appropriate uses of HRQL measurement in clinical trial and
      community practice settings.

PMID- 11232667
TI  - The diagnostic pursuit of gastrointestinal symptoms.
AB  - The present article attempts to model the reasoning underlying the process of
      diagnostic workup in a patient with GI symptoms. Diagnostic reasoning consists of
      two consecutive and repetitive steps. Test procedures help to contract a list of
      multiple competing diagnoses to one focal diagnosis. In a subsequent step, the
      focal diagnosis again becomes expanded to a second list of new diagnoses that are
      more precise than those on the first list. In the process of expansion, the focal
      diagnosis itself serves as a test with its own sensitivity values to generate the
      second list of associated diagnoses. The process of contraction and expansion
      repeats itself, until the focal diagnosis of the last contraction is no longer
      expansible or until diagnostic knowledge gained from further expansion loses
      therapeutic relevance. The process of contraction and expansion can be formalized
      by Bayes' formula.

PMID- 11232668
TI  - Nonerosive reflux disease--current concepts and dilemmas.
AB  - Nonerosive reflux disease is defined as the presence of typical symptoms of
      gastroesophageal reflux disease caused by intraesophageal acid in the absence of
      visible esophageal mucosal injury at endoscopy. Recent studies demonstrate that
      it is a chronic disease with a significant impact on quality of life, and it is
      very common in primary care settings. Treatment with acid inhibitory agents is
      effective, and proton pump inhibitors are the most effective form of therapy.

PMID- 11232669
TI  - Clinicopathological features of superficial spreading and nonspreading squamous
      cell carcinoma of the esophagus.
AB  - OBJECTIVES: Superficially spreading carcinoma of the esophagus, consisting mainly
      of intraepithelial carcinoma, is not as rare as was previously thought. Despite
      the surgical significance of this entity, no general definition has been
      established, and the clinical features of this disease remain to be clarified.
      METHODS: A total of 54 patients with superficial carcinoma of the esophagus
      (defined as carcinoma limited to the epithelium or superficially invading the
      lamina propria or submucosa) were classified into two groups according to the
      longitudinal extent of the lesion. A total of 13 patients with superficially
      spreading carcinoma (defined as a superficial carcinoma measuring >5 cm and
      consisting mainly of intraepithelial carcinoma) were compared to 41 patients with
      nonspreading esophageal carcinoma. RESULTS: One patient with superficially
      spreading carcinoma had a positive resection margin because of multiple cancerous
      lesions. The only significant difference in the clinical and pathological
      features of the two groups was a higher prevalence of associated multiple
      cancerous lesions in patients with the superficially spreading type. CONCLUSIONS:
      Superficially spreading carcinoma of the esophagus is often associated with
      multiple cancerous lesions. For endoscopists and esophageal surgeons, it is
      important to define the proximal extent of intraepithelial cancer and the
      presence of multiple cancerous lesions to perform curative resection.

PMID- 11232670
TI  - Relationship of iron-deficiency anemia with esophagitis and hiatal hernia:
      hospital findings from a prospective, population-based study.
AB  - OBJECTIVE: Iron-deficiency anemia is sometimes attributed to esophagitis and
      hiatal hernia; however, because these GI conditions are so common, such an
      association could be coincidental. We examined prospectively whether esophagitis
      and hiatal hernia increased the risk of iron-deficiency anemia in a national,
      population-based study. METHODS: The study population comprised 5069 adult
      participants in the first National Health and Nutrition Examination Survey, who
      were free of GI hemorrhage and anemia at baseline examination in 1971-1975 and
      who were hospitalized at some point during nearly 20 yr of follow-up. Rates of
      hospitalization with iron-deficiency or unspecified anemia were compared between
      patients with a hospital diagnosis of esophagitis or hiatal hernia and those who
      had not yet had a diagnosis of these disorders. Adjusted rate ratios were
      calculated using time-dependent, multivariable, proportional hazards analysis.
      RESULTS: During follow-up, 59 patients were hospitalized with esophagitis alone,
      140 with hiatal hernia alone, and 70 with both diagnoses. A total of 102
      participants were hospitalized with iron-deficiency anemia and 256 with
      unspecified anemia. Compared to those without a diagnosis of esophagitis or
      hiatal hernia, patients with a diagnosis of hiatal hernia had higher rates of
      subsequent hospitalization with iron-deficiency anemia. The hazard rate ratio
      (HRR) for hiatal hernia was 2.9 (95% confidence interval, 1.5-5.5). A trend was
      found for esophagitis with a HRR of 2.2 (95% confidence interval, 0.79-6.0).
      Results were similar with unspecified anemia as the outcome. CONCLUSIONS: Hiatal
      hernia should be considered as a possible cause of iron-deficiency anemia. The
      relationship of esophagitis with iron-deficiency anemia requires further study.

PMID- 11232671
TI  - Dysphagia without endoscopically evident disease: to dilate or not?
AB  - OBJECTIVES: It is not known whether patients with symptoms of dysphagia but
      normal upper endoscopy benefit from empiric esophageal dilation. The aim of this
      prospective study was to determine whether patients with solid food dysphagia and
      normal upper endoscopy have symptomatic benefit from empiric dilation using a
      through-the-scope balloon. METHODS: Patients who were seen for complaints of
      solid food dysphagia and who had normal endoscopic examinations at our
      institution from 1998 through 1999 were identified. Those patients who had agreed
      before sedation to participate in the study, if eligible, were randomized to
      either sham or balloon dilation using an 18-mm through-the-scope balloon at the
      time of esophagogastroduodenoscopy. All potentially eligible patients who had
      given provisional consent completed a dysphagia questionnaire and a 10-cm visual
      analog dysphagia scale before endoscopy. Follow-up questionnaires were completed
      on day 1 and at 3 months and 6 months after the procedure. The primary endpoint
      of the study was the patient's self-assessment of difficulty swallowing, based on
      the questionnaires. RESULTS: A total of 83 patients met the study criteria and
      were randomized to balloon dilation (n = 43) or sham (n = 40). The two groups
      were comparable in age, sex, severity of baseline dysphagia. and use of
      antireflux medication. Improvement in dysphagia comparing sham to balloon on day
      1 was 66% versus 67% (p = 0.99); at 3 months it was 82% versus 76% (p = 0.56);
      and at 6 months it was 84% versus 73% (p = 0.38). There were no reported
      complications in either group. CONCLUSION: The data from this prospective
      randomized, controlled study do not support the practice of empiric dilation in
      patients with symptoms of dysphagia without an endoscopically evident cause of
      dysphagia.

PMID- 11232672
TI  - Increased acid and bile reflux in Barrett's esophagus compared to reflux
      esophagitis, and effect of proton pump inhibitor therapy.
AB  - OBJECTIVES: Barrett's metaplasia is an acquired condition resulting from
      longstanding gastroesophageal reflux disease. Approximately 10% of esophagitis
      patients develop Barrett's esophagus. There is increasing evidence that
      duodenogastroesophageal reflux plays a role in the progression of disease. We
      further analyzed the correlation of acid and biliary reflux with reflux
      esophagitis and Barrett's esophagus and tested the effects of proton pump
      inhibitor therapy. METHODS: Patients with either reflux esophagitis (group 1) or
      Barrett's esophagus (group 2) prospectively underwent simultaneous 24-h
      esophageal pH and bile reflux testing without any therapy affecting acid
      secretion or GI motility. A total of 16 patients in group 1 and 18 patients in
      group 2 were tested again under proton pump inhibitor therapy. RESULTS: Acid and
      bile exposure were significantly increased in Barrett's patients (n = 23)
      compared to 20 esophagitis patients (median percentage of time that pH was <4 was
      24.6% vs 12.4%, p = 0.01, median percentage of time that bilirubin absorbance was
      >0.2 was 34.7% vs 12.8%, p < 0.05). During therapy, both acid and bile reflux
      decreased significantly in both groups. Median percentage of time that pH was <4
      and bilirubin absorbance was >0.2 before and during therapy was 18.2%/2.3% and
      29.8%/0.7% (p = 0.001 and p = 0.001) in Barrett's esophagus patients versus
      14.5%/3.6% and 21.5%/0.9% (p = 0.002 and p = 0.011) in esophagitis patients.
      There was no significant difference between the groups. In two esophagitis
      patients, bile reflux increased during therapy. CONCLUSIONS: There is a good
      correlation of the duration of esophageal exposure to acid and bile with the
      severity of pathological change in the esophagus. Both acid and bile reflux is
      significantly suppressed by proton pump inhibitor therapy with exceptions among
      individual esophagitis patients. The prolonged simultaneous attack of bile and
      acid may play a key role in the development of Barrett's metaplasia.

PMID- 11232673
TI  - Quality of life measurement clarifies the cost-effectiveness of Helicobacter
      pylori eradication in peptic ulcer disease and uninvestigated dyspepsia.
AB  - OBJECTIVES: Previous economic studies of Helicobacter pylori eradication in
      dyspepsia and peptic ulcer disease have not measured quality of life using
      utilities (preference probabilities), which are needed to compare the cost
      effectiveness of such treatment to other health care interventions. The goals of
      this study were to measure quality of life in patients with dyspepsia or peptic
      ulcer and apply these measurements to published models of disease management to
      determine cost-effectiveness in dollars per quality-adjusted life year (QALY)
      gained. METHODS: Utilities for dyspepsia and peptic ulcer disease were measured
      in adult patients (n = 73) on chronic acid suppression for peptic ulcer or ulcer
      like dyspepsia. Median utility values were applied to the results of published
      cost-effectiveness analyses and a previously validated dyspepsia model. Cost
      utility ratios for early H. pylori eradication in uninvestigated dyspepsia and
      peptic ulcer disease were then computed. RESULTS: The total disutility, or lost
      quality of life, for an ulcer was 0.11 QALY, of which 0.09 QALY was attributed to
      dyspeptic symptoms. After these results were incorporated into published studies,
      cost-utility ratios for ulcer treatment varied from $3,100 to $12,500 per QALY
      gained, whereas estimates for uninvestigated dyspepsia management ranged from
      $26,800 to $59,400 per QALY. Sensitivity analyses indicated a range of $1,300 to
      $27,300 per QALY for management of duodenal ulcer and $15,000 to $129,700 per
      QALY for dyspepsia. CONCLUSIONS: Strategies that emphasize early H. pylori
      eradication were cost-effective for patients with peptic ulcer and possibly cost
      effective for patients with uninvestigated dyspepsia, relative to other medical
      interventions. Dyspeptic symptoms cause significant disutility that should be
      incorporated in future cost-effectiveness analyses of treatment strategies.

PMID- 11232674
TI  - Negative effect of ranitidine on the results of urea breath test for the
      diagnosis of Helicobacter pylori.
AB  - OBJECTIVES: In analogy with proton pump inhibitors, H2-antagonists may also be
      responsible for false-negative results on urea breath test for the detection of
      Helicobacter pylori. In this study we assessed the frequency and duration of
      false-negative urea breath tests in patients given different doses of ranitidine.
      METHODS: A total of 120 consecutive dyspeptic patients infected with H. pylori on
      the basis of concomitant positive results of CLO-test, histology and urea breath
      test were recruited for this prospective, open, parallel-group study performed in
      an urban university gastroenterological clinic. They were randomized to receive
      an acute treatment with either ranitidine 300 mg once a day in the evening,
      ranitidine 300 mg once a day in the morning, ranitidine 150 mg b.i.d., or
      ranitidine 300 mg b.i.d. for 14 days. The urea breath test was performed on day
      14 while patients were still taking ranitidine, and on day 21, 1 wk after
      completion of therapy. The test was repeated on day 28 in those patients who were
      still negative on day 21. Duplicate breath samples were collected after ingestion
      of 75 mg 13C-urea plus citric acid. A delta value >5/1000 was considered
      positive. RESULTS: Of 118 patients infected with H. pylori, 15 (13%) had a
      negative urea breath test on day 14. The false-negative results were equally
      distributed among the four groups of ranitidine dosage. Nine of these patients
      reverted to positive at 7 days and the remaining six at 14 days after completion
      of therapy. CONCLUSIONS: Our study shows that ranitidine negatively affects the
      results of urea breath testing, independent of the given dosage. Patients
      undergoing this examination for H. pylori diagnosis should discontinue use of H2
      antagonists 2 wk before testing.

PMID- 11232675
TI  - Diagnosis of Helicobacter pylori infection: noninvasive methods compared to
      invasive methods and evaluation of two new tests.
AB  - OBJECTIVES: Current guidelines recommending Helicobacter pylori eradication
      treatment without performing endoscopy in certain patients highlight the
      importance of noninvasive tests. Our aim was to determine the accuracy of two new
      tests: the antigen stool test and Helicoblot 2.1 (an immunoblot used on serum) as
      well as the 13C urea breath test and ELISA serology in comparison to invasive
      tests for the pretreatment diagnosis of H. pylori infection. METHODS:
      Helicobacter pylori infection was diagnosed prospectively in 104 untreated
      patients using eight different tests. Invasive tests included culture, urease
      test (CLOtest), histology, and PCR; noninvasive tests included the 13C urea
      breath test, IgG serology (Pyloriset EIA-G), immunoblot (Helicoblot 2.1), and
      antigen stool detection (Premier Platinum HpSA). A predefined gold standard based
      on biopsy tests was used to define H. pylori status, as well as an empirical
      approach. RESULTS: There was no statistically significant difference between the
      different tests. The sensitivity of the noninvasive tests ranged between 88.9%
      and 95.6% (stool test: 88.9%, 95% CI: 82.7-95.1, and Helicoblot 2.1: 95.6%, 95%
      CI: 91.5-99.6) and the specificity ranged between 92.6 and 98.1% (stool test:
      94.4%, 95% CI: 84.6-98.8, and Helicoblot 2.1: 92.6%, 95% CI: 91.5-96.2) when a
      predefined gold standard was used. CONCLUSIONS: Most tests had sensitivities,
      specificities, and predictive values >90%. The noninvasive tests are accurate for
      the diagnosis of H. pylori infection. Helicoblot 2.1 performed as well as the
      best ELISA kit. The HpSA is a promising direct noninvasive test that can be
      applied easily to evaluate H. pylori status.

PMID- 11232676
TI  - Do some patients with Helicobacter pylori infection benefit from an extension to
      2 weeks of a proton pump inhibitor-based triple eradication therapy?
AB  - OBJECTIVES: Seven-day proton pump inhibitor (PPI)-based triple therapies are the
      first-line anti-Helicobacter pylori regimens; to date, however, there is still no
      agreement concerning all the predictors of H. pylori cure under these regimens.
      The aim of this prospective study was to evaluate whether patients with certain
      pretreatment characteristics may benefit from an extension from 1 to 2 wk of
      treatment with lansoprazole, amoxycillin, and clarithromycin. METHODS: A total of
      142 patients with H. pylori infection ascertained by means of gastric
      histopathology and 13C urea breath test (UBT) participated in this study. In all
      patients H. pylori density was determined at histology both on antral and corpus
      biopsies, and H. pylori culture with antibiotic susceptibility testing; IgG anti
      H. pylori titers were also determined before therapy. Patients were randomized to
      receive 1-wk versus 2-wk of treatment with lansoprazole (30 mg b.i.d.),
      clarithromycin (500 mg b.i.d.), and amoxycillin (1 g b.i.d.). The association
      between eradication and potential predictors was analyzed by means of
      unconditional logistic regression models and stratified according to the duration
      of treatment. A stepwise regression analysis was performed to identify variables
      discriminated between subjects, using eradication status as the dependent
      variable. RESULTS: The overall eradication rates for 1- and 2-wk treatments were
      74.6% and 85.9% (intention-to-treat analysis) and 81.5% and 89.1% (per-protocol
      analysis), respectively (p = NS). Multivariate discriminant analysis selected as
      the variables independently related to eradication cigarette smoking (OR = 3.98),
      delta of 13C-UBT higher than 35 (OR = 9.21) and IgG anti-H. pylori titer > or =
      93 (OR = 0.24) for the whole series of subjects. Stratified analysis according to
      the duration of therapy selected H. pylori density as the only predictor of
      eradication in the group treated for 1 wk (OR = 8.11). In contrast, no
      significant predictors were found in the group treated for 2 wk. CONCLUSIONS:
      Patients with a high intragastric bacterial load, as detected by histology (grade
      3) or 13C-UBT (delta > 35) may benefit from an extension to 2 wk of triple
      therapy with lansoprazole, amoxycillin, and clarithromycin.

PMID- 11232677
TI  - A randomized, pharmacokinetic and pharmacodynamic, cross-over study of duodenal
      or jejunal administration compared to nasogastric administration of omeprazole
      suspension in patients at risk for stress ulcers.
AB  - OBJECTIVES: The aim of this study was to characterize absorption and pH control
      of simplified omeprazole suspension (SOS), 2 mg/ml in 8.4% sodium bicarbonate,
      administered via the nasogastric versus jejunal or duodenal route. METHODS: Nine
      critically ill surgical patients, NPO and mechanically ventilated, were enrolled
      in this randomized cross-over study. Patients received a single 40 mg dose of SOS
      by the nasogastric and either the jejunal or duodenal route. Twenty-four-hour
      continuous intragastric pH monitoring was performed during the study period.
      Sequential blood samples were collected over 24 h to characterize SOS absorption
      and pharmacokinetic parameters. RESULTS: Nasogastric administration of SOS
      resulted in lower maximum mean +/- SD serum concentrations compared to
      jejunal/duodenal dosing (0.970 +/- 0.436 vs 1.833 +/- 0.416 microg/ml, p =
      0.006). SOS absorption was significantly slower when administered via nasogastric
      tube (108.3 +/- 42.0 vs 12.1 +/- 7.9 min, p < 0.001). However, all routes of
      administration resulted in similar SOS area under the serum concentration-time
      curves (AUC(0-infinity)) (415.1 +/- 291.8 vs 396.7 +/- 388.1 microg x min/ml, p =
      0.91) [corrected]. Mean intragastric pH values remained >4 at 1 h after SOS
      administration and remained >4 for the entire 24-h study (6.32 +/- 1.04, 5.57 +/-
      1.15, nasogastric vs jejunal/duodenal, p = 0.015), regardless of administration
      route. CONCLUSIONS: In critically ill surgical patients, pharmacokinetic
      parameters and subsequent pH control after the administration of SOS are similar
      by the jejunal, nasogastric, or duodenal route. SOS suspension offers an
      alternative acid control measure when patients are unable to take oral
      medications, yet have an enteral tube in place.

PMID- 11232678
TI  - Paraneoplastic gastrointestinal motor dysfunction: clinical and laboratory
      characteristics.
AB  - OBJECTIVES: The aim of this study was to describe the clinical, manometric, and
      serological characteristics of 12 patients with paraneoplastic GI motor
      dysfunction and to assess the contributory role of diagnostic tests. METHODS:
      Twelve patients diagnosed with malignant tumors and GI motor dysfunction were
      identified at the Mayo Clinic from 1985 to 1996. RESULTS: Cancers identified
      were: nine small cell lung carcinoma (SCLC), one anaplastic lung adenocarcinoma,
      one retroperitoneal lymphoma, and one ovarian papillary serous adenocarcinoma. GI
      symptoms preceded the tumor diagnosis in all cases of SCLC (mean, -8.7 months,
      range, -1 to -24 months, n = 9). The diagnosis of a malignant tumor preceded the
      onset of GI symptoms in the three patients with other neoplasms (6, 12, and 24
      months). Five of the nine patients found to have SCLC had no evidence of tumor on
      initial chest x-ray. One or more paraneoplastic autoantibodies were found in 10
      of the 11 patients tested by autoimmune serology. Type 1 antineuronal nuclear
      antibody (ANNA-1 or anti-Hu) was detected in eight of the nine patients with SCLC
      (one patient was not tested). The patient with ovarian carcinoma had type 1
      Purkinje cell cytoplasmic antibody (PCA-1 or anti-Yo). N-type calcium channel
      antibodies were found in one patient with SCLC, one with a retroperitoneal B cell
      lymphoma, and one with ovarian carcinoma. Gastric emptying was delayed in 89%
      (eight of nine tested) and 80% (four of five tested) had esophageal dysmotility.
      Autonomic reflex tests were abnormal in the seven patients tested. CONCLUSIONS:
      The diagnosis of paraneoplastic GI motor dysfunction requires a high index of
      clinical suspicion. A panel of serological tests for paraneoplastic
      autoantibodies, scintigraphic gastric emptying, and esophageal manometry are
      useful as first-line screening tests. Seropositivity for ANNA-1, PCA-1, or N-type
      calcium channel-binding antibodies should prompt further evaluation for an
      underlying malignancy even when routine imaging studies are negative.

PMID- 11232679
TI  - Absence of abdominal pain in older persons with endoscopic ulcers: a prospective
      study.
AB  - OBJECTIVE: In a retrospective study we reported absence of abdominal pain in 35%
      of elderly patients with peptic ulcer disease. We now report a prospective study
      on this question. METHODS: Patients undergoing upper GI endoscopy were
      systematically questioned before endoscopy. A reproducible method for identifying
      the location of symptoms was used. Among patients referred for upper endoscopy,
      there was no selection of patients for study purposes as all had strong
      indications, such as pain, dyspepsia, GI bleeding, weight loss, or anemia.
      Patients were divided into two groups according to age: A younger group
      consisting of patients <50 yr (mean, 33.6 yr) and an older group >60 yr (mean,
      70.9 yr). RESULTS: A total of 277 patients were included in the study. There was
      no significant difference in reported use of medications, alcohol, or cigarette
      use between the groups. Of the 106 patients with peptic ulcer, 15 (14.2%) had not
      experienced pain. Abdominal pain was absent in 5 (6.9%) of the younger patients
      and 10 (29.4%) of the older patients. The difference was significant using the
      chi2 method (p = 0.004). A trend toward an even higher proportion of pain-free
      peptic ulcer disease was noted in the elderly female group (37.5%), but it did
      not reach statistical significance. CONCLUSIONS: Absence of abdominal pain is
      confirmed in approximately 30% of elderly patients with peptic ulcer disease.

PMID- 11232680
TI  - Severe gastrointestinal bleeding after hematopoietic cell transplantation, 1987
      1997: incidence, causes, and outcome.
AB  - OBJECTIVE: Severe GI bleeding after hematopoietic cell transplantation is
      commonly due to lesions that are unusual in nontransplant patients. The frequency
      of GI bleeding appears to have decreased over the last decade, but the reasons
      have not been readily apparent. We sought to determine the incidence of severe
      bleeding during two time periods, to describe the causes and outcomes of
      bleeding, and to analyze the reasons behind an apparent decline in severe
      bleeding over the decade covered. METHODS: During 1986-1987 and 1996-1997, we
      followed all patients with and without severe bleeding at our institution, a
      marrow transplant center. RESULTS: Over this decade, the incidence of severe
      bleeding declined from 50/467 (10.7%) to 15/635 (2.4%) (p < 0.0001). Overall
      mortality from intestinal bleeding declined from 3.6% to 0.9% (p = 0.002), but
      mortality in those with bleeding remained high (34% vs 40%). The onset (day 42 vs
      47) and platelet counts (35,994 vs 37,600/microl) were similar, but the sites and
      causes of bleeding were different. During 1986-1987, 27/50 patients bled from
      multiple GI sites, viral and fungal ulcers, or graft-versus-host disease (GVHD).
      Over the decade, bleeding from GVHD had decreased 80% (p < 0.0001), and bleeding
      from viral (p < 0.0001) and fungal (p = 0.023) ulcers almost disappeared.
      CONCLUSIONS: The incidence of severe GI bleeding has declined significantly over
      the last decade because of prevention of viral and fungal infections and severe
      acute GVHD. However, severe bleeding after transplant remains a highly morbid
      event, particularly among patients with GVHD.

PMID- 11232681
TI  - Computed tomographic colonography and conventional colonoscopy for colon
      diseases: a prospective, blinded study.
AB  - OBJECTIVES: Computed tomographic (CT) colonography or virtual colonoscopy is a
      new diagnostic method for the colon and rectum, developed on the basis of spiral
      computed axial tomography and employing virtual reality technology. The aim of
      this study was to determine the sensitivity, specificity, and diagnostic accuracy
      of CT colonography compared with colonoscopy in a prospective, blinded study in
      one single institution in Italy. METHODS: Ninety-nine patients randomly selected
      among those attending the open-access endoscopy unit for diagnostic colonoscopy
      underwent colonoscopy and spiral CT. The images obtained were transmitted to
      generate the virtual colonoscopy pictures. A supervisor compared the results with
      the findings of conventional colonoscopy. RESULTS: CT colonography diagnosed
      seven of eight tumors, one being missed because the patient had been inadequately
      prepared. In 28 patients, CT colonography identified 26 polyps of 45 (57.8%
      sensitivity, 92.6% specificity, 86.7% positive predictive value), regardless of
      their size. The sensitivity in detecting colonic polyps was 31.8% (7/22) in the
      first 25 cases and 91.6% (11/12) in the last 20 patients. CT colonography missed
      one flat adenoma, some angioectasias and colonic lesions because of portal
      hypertension in one patient, Crohn's disease ulcers in two patients, and
      ulcerative colitis lesions in three. CONCLUSIONS: CT colonography shows poor
      sensitivity for identifying colonic polyps and does not always detect neoplastic
      lesions. Flat lesions are impossible to see by this method.

PMID- 11232682
TI  - Evaluation of mediastinal masses by endoscopic ultrasound and endoscopic
      ultrasound-guided fine needle aspiration.
AB  - OBJECTIVE: Interest has been growing in using endoscopic ultrasound and
      endoscopic ultrasound-guided fine needle aspiration in the evaluation of
      mediastinal masses. The purpose of this study was to review the spectrum of
      mediastinal masses encountered using endoscopic ultrasound. METHODS: We reviewed
      all cases of mediastinal masses examined by endoscopic ultrasound, with or
      without endoscopic ultrasound-guided fine needle aspiration, prospectively
      gathered from our electronic database from April 1995 to July 2000. RESULTS: Of
      1447 upper endoscopic ultrasound examinations, 33 (2.3%) involved a mediastinal
      mass. Sixty-one percent of the patients were male and the average age was 65 yr.
      Fifty-five percent of patients had dysphagia, 48 percent experienced weight loss,
      and only 12 percent were totally asymptomatic. Seventy-three percent had masses
      by chest CT. Sixty-seven percent were ultimately found to be malignant, 21
      percent were solid benign lesions, and four were cystic. Only two lesions were
      resected. Endoscopic ultrasound-guided fine needle aspiration was used in 76
      percent of all patients. The median survival of patients with malignant lesions
      was only 87 days. CONCLUSIONS: Lesions of the deep mediastinum are often
      difficult to conclusively diagnose with nonendoscopic studies. Endoscopic
      ultrasound and endoscopic ultrasound-guided fine needle aspiration can easily
      access this region to aid in the diagnosis and management of these lesions.

PMID- 11232683
TI  - Endoscopic ultrasound-guided celiac plexus block for managing abdominal pain
      associated with chronic pancreatitis: a prospective single center experience.
AB  - OBJECTIVE: In our previous randomized trial, we suggested a possible role for
      endoscopic ultrasound (EUS) guided celiac plexus block in the treatment of
      abdominal pain associated with chronic pancreatitis. The purpose of this study
      was to evaluate our prospective experience with EUS-guided celiac plexus block
      for controlling pain attributed to chronic pancreatitis, including follow-up on
      response rates and complications. METHODS: All subjects enrolled had documented
      chronic pancreatitis by ERCP and EUS criteria and presented with chronic
      abdominal pain unresponsive to current treatment options. All were treated with
      EUS-guided celiac plexus block under the guidance of linear array endosonography
      using a 22-gauge FNA needle (GIP, Mediglobe Inc., Tempe, AZ) inserted on each
      side of the celiac area, followed by injection of 10 cc bupivacaine (0.25%) and 3
      cc (40 mg) triamcinolone on each side of the celiac plexus. Individual pain
      scores, based on a visual analog scale (0-10), were determined preblock and
      postblock by a nurse at 2, 7, 14 days and monthly thereafter. Subjects also rated
      their overall comfort level during the EUS procedure. RESULTS: EUS-guided celiac
      plexus block was performed in 90 subjects (40 males, 50 females) having a mean
      age of 45 yr (range 17-76 yr) between July 1, 1995 and December 30, 1996. A
      significant improvement in overall pain scores occurred in 55% (50/90) of
      patients. The mean pain score decreased from 8 to 2 post EUS celiac block at both
      4 and 8 wk follow-up (p < 0.05). In 26% of patients there was persistent benefit
      beyond 12 wk, and 10% still had persistent benefit at 24 wk, including three
      patients who were pain-free between 35 and 48 wk. Younger patients (<45 yr of
      age) and those having previous pancreatic surgery for chronic pancreatitis were
      unlikely to respond to the EUS-guided celiac block. Three patients experienced
      diarrhea post EUS celiac block, which resolved in 7-10 days; however, it is
      unclear whether this diarrhea was due to the block or to refractory disease. A
      cost comparison between the EUS ($1200) and CT ($1400) techniques shows the EUS
      celiac block to be less costly and perhaps more cost efficient in a subset of
      subjects. CONCLUSIONS: EUS-guided celiac plexus block appears to be safe,
      effective, and economical for controlling pain in some patients with chronic
      pancreatitis. Younger patients (<45 yr) and those having prior pancreatic surgery
      for chronic pancreatitis do not appear to benefit from this technique.
      Prophylactic antibiotics should be considered if acid suppressing agents are
      being taken.

PMID- 11232684
TI  - Complications of diagnostic and therapeutic ERCP: a prospective multicenter
      study.
AB  - OBJECTIVES: Diagnostic and therapeutic endoscopic retrograde
      cholangiopancreatography (ERCP/ES) can be associated with unforeseeable
      complications, especially when involving postprocedural pancreatitis. The aim of
      the study was to investigate risk factors for complications of ERCP/ES in a
      prospective multicentric study. METHODS: One hundred fifty variables were
      prospectively collected at time of ERCP/ES and before hospital discharge over 2
      years, in consecutive patients undergoing the procedure in nine endoscopic units
      in the Lombardy region of Italy. More than 150 ERCPs were performed in each
      center per year by a single operator or by a team of no more than three
      endoscopists. RESULTS: Two thousand four hundred sixty-two procedures were
      performed; 18 patients were discharged because the papilla of Vater was not
      reached (duodenal obstruction, previous gastrectomy, etc.). Two thousand four
      hundred forty-four procedures were considered in 2103 patients. Overall
      complications occurred in 121 patients (4.95% of cases): pancreatitis in 44
      patients (1.8%), hemorrhage in 30 (1.13%), cholangitis in 14 (0.57%), perforation
      during ES in 14 (0.57%), and others in 14 (0.57%); deaths occurred in three
      patients (0.12%). In multivariate analysis, the following were significant risk
      factors: a) for pancreatitis, age (< or = 60 yr), use of precutting technique,
      and failed clearing of biliary stones, and b) for hemorrhage, precut
      sphincterotomy and obstruction of the orifice of the papilla of Vater.
      CONCLUSIONS: The results of our study further contribute to the assessment of
      risk factors for complications related to ERCP/ES. It is crucial to identify high
      risk patients to reduce complications of the procedures.

PMID- 11232685
TI  - A comparison of serum trypsinogen-2 and trypsin-2-alpha1-antitrypsin complex with
      lipase and amylase in the diagnosis and assessment of severity in the early phase
      of acute pancreatitis.
AB  - OBJECTIVE: The aim of the study was to compare the recently introduced laboratory
      markers trypsinogen-2 and trypsin-2-alpha1 antitrypsin complex (trypsin-2-AAT) in
      serum with lipase and amylase in the diagnostic and prognostic evaluation of
      patients with acute pancreatitis (AP). METHODS: The analytes were measured on
      admission in 64 consecutive patients with AP and in 30 controls with acute
      abdominal disease of extrapancreatic origin. Twenty-one patients had severe and
      43 mild AP. As reference methods we used serum amylase and C-reactive protein.
      RESULTS: In subjects with AP, elevated trypsinogen-2 values (> or = 90 microg/L)
      were observed in 63 patients (98%), trypsin-2-AAT values (> or = 12 microg/L) in
      64 patients (100%), lipase values (> or = 200 U/L) in 64 patients (100%), and
      amylase values (> or = 300 IU/L) in 62 patients (97%). The diagnostic accuracy of
      the markers was evaluated by receiver operating characteristic (ROC) analysis. On
      admission, trypsinogen-2, trypsin-2-AAT, lipase, and amylase differentiated
      patients with AP from controls with high accuracy and ROC analyses showed similar
      areas under the ROC curves (AUC) for trypsinogen-2 (AUC 0.960), trypsin-2-AAT
      (0.948), lipase (AUC 0.947), and amylase (AUC 0.930). For differentiation between
      severe and mild AP, trypsin-2-AAT (AUC 0.805) was slightly better than
      trypsinogen-2 (AUC 0.792), and they were both clearly better than lipase (AUC
      0.583), C-reactive protein (AUC 0.519), or amylase (AUC 0.632) (p < 0.05).
      CONCLUSIONS: All the markers studied showed high accuracy for differentiating
      between AP and extrapancreatic diseases. However, trypsinogen-2 and trypsin-2-AAT
      displayed the best accuracy for predicting a severe AP already at admission,
      which makes these markers superior for clinical purposes.

PMID- 11232686
TI  - Role of differential neuroaxial blockade in the evaluation and management of pain
      in chronic pancreatitis.
AB  - OBJECTIVES: Chronic pancreatic pain is difficult to treat. Surgical and medical
      therapies directed at reducing pain have met with little long-term success. In
      addition, there are no reliable predictors of response including pancreatic duct
      diameter. A differential neuroaxial blockade allows characterization of chronic
      abdominal pain into visceral and nonvisceral pain origins and may be useful as a
      guide to the treatment. Pain from an inflamed, and scarred pancreas should be
      visceral in origin. The purpose of our study was to determine the frequency with
      which patients with chronic pancreatitis have visceral pain and whether our
      modified differential neuroaxial blockade technique using thoracic epidural
      analgesia can accurately predict which patients will respond to medical or
      surgical therapy. METHODS: We retrospectively reviewed the medical records of
      patients with a firmly established diagnosis of chronic pancreatitis (Cambridge
      classification, calcifications) who had undergone a differential neuroaxial block
      for their chronic abdominal pain evaluation. Patient demographics and medical or
      surgical treatment for pancreatic pain was recorded. Response to therapy was
      defined by a 50% reduction in pain by verbal response score. RESULTS: A total of
      23 patients were identified. Alcohol was the most common etiology for chronic
      pancreatitis (15 of 23, 55%). Surprisingly, the majority of chronic pancreatitis
      patients had nonvisceral pain (18 of 23, 78%) and only 22% (5 of 23) had visceral
      pain by differential neuroaxial block. Four of five patients (80%) with visceral
      pain responded to therapy, whereas only 5 of 17 (29%) of patients with
      nonvisceral pain responded. CONCLUSIONS: Surprisingly, patients with chronic
      pancreatitis commonly have nonvisceral pain. Differential neuroaxial blockade can
      predict which patients will respond to therapy.

PMID- 11232687
TI  - Incidence and management of esophageal stricture formation, ulcer bleeding,
      perforation, and massive hematoma formation from sclerotherapy versus band
      ligation.
AB  - OBJECTIVES: The aim of this study was to compare the incidence and endoscopic
      management of esophageal stricture formation, significant ulcer bleeding, massive
      esophageal hematoma, and perforation resulting from endoscopic band ligation or
      sclerotherapy of esophageal varices. METHODS: Consecutive
      esophagogastroduodenoscopies in which band ligation or sclerotherapy was
      performed for acute or obliterative therapy were entered into a computerized
      endoscopy database during a 7-yr period. Patients were excluded if they died
      within 72 h of treatment session from complications unrelated to the procedure.
      Sclerotherapy was performed using a 25-gauge needle with 1.5% sodium tetradecyl
      sulfate and banding was primarily performed with a Wilson-Cook 6 or 10 shooter.
      Complications were assessed at scheduled endoscopy and outpatient clinic visits,
      review of quality assurance data tallied on a monthly basis, and patient records.
      RESULTS: Two hundred twenty-one cases of sclerotherapy were performed in 59
      patients compared to 110 cases of band ligation in 52 patients. Five patients
      were excluded because of death within 72 h of the procedure. The incidence of
      complications from sclerotherapy:banding on a per patient basis included:
      esophageal stricture formation 25.6%:1.9%, ulcer bleed 25.4%:5.7%, esophageal
      perforation 2.2%:0%, and massive esophageal hematoma 1.6%:0%. A significant
      difference in complications between sclerotherapy and band ligation was noted for
      both stricture formation (p < 0.0005) and ulcer bleeding (p < 0.0001). The
      majority of ulcer bleeds required no therapeutic intervention, whereas stricture
      formation required multiple dilation sessions. CONCLUSIONS: Band ligation has a
      significantly lower incidence of stricture formation and ulcer bleeding compared
      to sclerotherapy. The majority of complications can be managed with endoscopic
      interventions.

PMID- 11232688
TI  - The use of 1H magnetic resonance spectroscopy in inflammatory bowel diseases:
      distinguishing ulcerative colitis from Crohn's disease.
AB  - OBJECTIVES: The distinction between the two major forms of inflammatory bowel
      diseases (IBD), i.e., ulcerative colitis (UC) and Crohn's disease is sometimes
      difficult and may lead to a diagnosis of indeterminate colitis. We have used 1H
      magnetic resonance spectroscopy (MRS) combined with multivariate methods of
      spectral data analysis to differentiate UC from Crohn's disease and to evaluate
      normal-appearing mucosa in IBD. METHODS: Colon mucosal biopsies (45 UC and 31
      Crohn's disease) were submitted to 1H MRS, and multivariate analysis was applied
      to distinguish the two diseases. A second study was performed to test
      endoscopically and histologically normal biopsies from IBD patients. A classifier
      was developed by training on 101 spectra (76 inflamed IBD tissues and 25 normal
      control tissues). The spectra of 38 biopsies obtained from endoscopically and
      histologically normal areas of the colons of patients with IBD were put into the
      validation test set. RESULTS: The classification accuracy between UC and Crohn's
      disease was 98.6%, with only one case of Crohn's disease and no cases of UC
      misclassified. The diagnostic spectral regions identified by our algorithm
      included those for taurine, lysine, and lipid. In the second study, the
      classification accuracy between normal controls and IBD was 97.9%. Only 47.4% of
      the endoscopically and histologically normal IBD tissue spectra were classified
      as true normals; 34.2% showed "abnormal" magnetic resonance spectral profiles,
      and the remaining 18.4% could not be classified unambiguously. CONCLUSIONS: There
      is a strong potential for MRS to be used in the accurate diagnosis of
      indeterminate colitis; it may also be sensitive in detecting preclinical
      inflammatory changes in the colon.

PMID- 11232689
TI  - Anti-Saccharomyces cerevisiae mannan antibodies and antineutrophil cytoplasmic
      autoantibodies in Greek patients with inflammatory bowel disease.
AB  - OBJECTIVES: The combined measurement of perinuclear antineutrophil cytoplasmic
      autoantibodies (pANCA) and anti-Saccharomyces cerevisiae mannan antibodies (ASCA)
      has recently been suggested as a valuable diagnostic approach in inflammatory
      bowel disease (IBD). The aim of this study was to assess the value of detecting
      pANCA and ASCA in the differentiation between ulcerative colitis (UC) and Crohn's
      disease (CD) in a Greek population with IBD. METHODS: Sera were collected from
      157 patients with IBD (97 with UC, 56 with CD, and four with indeterminate
      colitis) and 150 healthy controls. Determination of pANCA was performed by a
      standard indirect immunofluorescence technique on ethanol-fixed granulocytes and
      ASCA by an ELISA assay. RESULTS: In patients with UC, sensitivity, specificity,
      positive predictive value, and negative predictive value of the pANCA test was
      67%, 84%, 93%, and 46% respectively. These values did not change significantly
      when the combination of positive pANCA and negative ASCA was used. ASCA test in
      diagnosing CD yielded a sensitivity, specificity, positive predictive value, and
      negative predictive value of 39%, 89%, 54%, and 81%. The combination of pANCA
      negative and ASCA positive increased the positive predictive value to 77% and it
      was associated with small bowel disease. CONCLUSIONS: A positive pANCA test in
      Greek patients has a diagnostic value in confirming a diagnosis of UC.
      Measurement of pANCA and ASCA together has a rather limited value in the
      differential diagnosis between UC and CD but may be of help in studying disease
      heterogeneity.

PMID- 11232690
TI  - Alosetron improves quality of life in women with diarrhea-predominant irritable
      bowel syndrome.
AB  - OBJECTIVES: The aim of this study was to assess the impact of alosetron, a
      treatment recently approved in the United States for irritable bowel syndrome in
      diarrhea-predominant female patients, on health-related quality of life. METHODS:
      Quality of life was assessed as part of two 12-wk randomized, double-blind,
      placebo-controlled irritable bowel syndrome studies comparing alosetron 1 mg
      b.i.d. with placebo (S3BA3001 and S3BA3002). Patients completed a validated
      disease-specific quality of life questionnaire, the Irritable Bowel Syndrome
      Quality of Life Questionnaire (IBSQOL), at baseline and at the 12-wk or final
      visit. The clinical relevance of data were also evaluated by a minimal meaningful
      difference instrument. RESULTS: A total of 626 and 647 patients were enrolled in
      studies S3BA3001 and S3BA3002, respectively. Approximately 70% of patients in
      each study had diarrhea-predominant IBS. In diarrhea-predominant patients
      enrolled in S3BA3001, statistically significant (p < 0.05) improvements with
      alosetron versus placebo were observed on all nine IBSQOL scales (emotional
      health, mental health, sleep, energy, physical functioning, food/diet, social
      functioning, role-physical, and sexual relations) and for all but one scale
      (mental health) in S3BA3002. In both studies, a significantly greater percentage
      of patients treated with alosetron (p < 0.05) experienced clinically meaningful
      improvement on three of the nine IBSQOL scales (food/diet, social functioning,
      and role-physical) compared with patients treated with placebo. Patients treated
      with alosetron did not show worsening in any quality of life domain compared with
      patients treated with placebo. CONCLUSIONS: These results in women with diarrhea
      predominant IBS demonstrate that alosetron significantly improves health-related
      quality of life.

PMID- 11232691
TI  - Diarrhea- and constipation-predominant IBS patients differ in postprandial
      autonomic and cortisol responses.
AB  - OBJECTIVE: As the primary link between brain and gut, autonomic and endocrine
      dysfunction may play a role in the pathophysiology of the irritable bowel
      syndrome (IBS). The aim of this study was to assess autonomic, endocrine, and
      symptomatic responses to food intake in diarrhea-predominant and constipation
      predominant IBS patients, compared to normals. METHODS: Twelve women with
      diarrhea-predominant or alternating IBS (IBS-D), 12 women with constipation
      predominant IBS (IBS-C), and 20 healthy women participated. GI symptoms, saliva
      cortisol concentration, heart rate, and heart rate variability were assessed at
      baseline and after a meal. Spectral analysis of heart rate variability was used
      as a measure of the sympathovagal regulation of the heart rate. RESULTS: Both
      groups of IBS patients showed a significant postprandial increase in GI symptoms.
      IBS-D showed a significant increase in the low frequency/high frequency band
      ratio and a decrease in the high frequency band power during the first postmeal
      period, which was significantly different, not only from controls, but also from
      IBS-C. IBS-D also showed a significant postprandial increase in cortisol, which
      was not evident in controls or IBS-C. There was a significant correlation between
      the vagal response and the postprandial increase in GI symptoms in IBS-D (r =
      0.6, p < 0.05). CONCLUSIONS: These findings support the notion that the IBS
      symptom groups are characterized by different physiological responses to visceral
      stimuli, and point to a role of autonomic pathways in IBS symptomatology.

PMID- 11232692
TI  - Increased nitrite and nitrate concentrations in sera and urine of patients with
      cholera or shigellosis.
AB  - OBJECTIVES: Nitric oxide (NO) is an important regulator of cell function. In the
      intestine, NO regulates blood flow, peristalsis, secretion, and is associated
      with inflammation and tissue injury. The objectives of this study were to assess
      and compare the role of NO in cholera, a noninflammatory enteric infection, and
      in shigellosis, a bacterial inflammation of the colon. METHODS: We determined
      serum and urinary concentrations of nitrite and nitrate during acute illness and
      early convalescence in 45 hospitalized children: 24 with cholera and 21 with
      shigellosis; 18 healthy children served as controls. Nitrite and nitrate
      concentrations were determined spectrophotometrically using Greiss reaction
      dependent enzyme assay. RESULTS: Serum nitrite and nitrate concentrations were
      significantly (p < 0.05) increased during acute illness compared to the early
      convalescence in both cholera and shigellosis. Urinary nitrite and nitrate
      excretions were significantly (p < 0.01) increased during acute disease in
      shigellosis, but not in cholera. Nitrite concentrations correlated with stool
      volume (r2 = 0.851) in cholera and with leukocytosis (r2 = 0.923) in shigellosis.
      CONCLUSIONS: Both cholera and shigellosis are associated with increased
      production of NO, suggesting its pathophysiologic roles in these diseases.

PMID- 11232693
TI  - Clinical and endoscopic features of nonsteroidal anti-inflammatory drug-induced
      colonic ulcerations.
AB  - OBJECTIVE: Clinical and endoscopic features of nonsteroidal anti-inflammatory
      drug (NSAID)-induced colonic ulcerations have not been fully investigated.
      METHODS: During a 3-yr period from April 1996 to March 1999, 6076 subjects
      underwent total colonoscopy at our institutions. Among them, the diagnosis of
      NSAID-induced colonic ulceration was made by their clinical and colonoscopic
      findings. All patients diagnosed as having this disease underwent upper endoscopy
      and follow-up colonoscopy. Clinical features, serial changes in colonoscopic
      findings, and upper GI lesions were analyzed. RESULTS: Among the subjects, 14
      patients were diagnosed as having NSAID-induced ulcerations. Seven patients were
      complicated by renal failure. Three patients had gastric ulcers concurrently.
      Eleven patients had colonic lesions in the ileocecal region. In 13 of 14
      patients, initial colonoscopy demonstrated sharply demarcated, semilunar or
      circumferential ulcers without stricture formation. After discontinuance of
      NSAIDs, improvement of the ulcers without stricture or inflammatory polyps could
      be confirmed 3-10 wk later. In one patient with diaphragm-like stricture, follow
      up colonoscopy performed 2 yr later demonstrated resolution of circumferential
      ulcer. CONCLUSIONS: NSAID-induced colonic ulceration may occur more frequently
      than previously recognized. Frank ulcerations, rather than stricture formation,
      seem to be the typical colonoscopic signs of NSAID-induced colonic ulceration.

PMID- 11232694
TI  - The prognostic value, in active ulcerative colitis, of an increased intensity of
      colonic perivisceral fat signal on magnetic resonance imaging with ferumoxil.
AB  - OBJECTIVE: In active ulcerative colitis (UC), magnetic resonance imaging (MRI)
      with ferumoxil, a superparamagnetic oral contrast agent, accurately evaluates, in
      our experience, the increased wall thickness and frequently shows a stronger
      perivisceral fat signal intensity (PFSI). The aim of our study was to evaluate
      the clinical significance of these MRI findings in active UC. METHODS: Twenty
      four consecutive patients affected by moderate pancolitis were enrolled. At
      entry, each patient underwent MRI with ferumoxil to evaluate wall thickness and
      PFSI. Two groups of patients were individuated: group A (increased PFSI) and
      group B (normal PFSI). After obtaining remission, the number of relapses and, at
      each flare-up, the clinical activity index (CAI) were evaluated in all patients
      in a 2-yr follow-up period. The mean CAI was calculated at the end of the follow
      up in each patient. Where there was colectomy, a complete histological
      examination of the colon was performed. RESULTS: PFSI was increased in 16
      patients (group A) and was normal in the remainder (group B). There was a
      significant difference of wall thickness, number of relapses/yr, and mean CAI
      between the two groups of patients. No difference was observed with regard the
      duration of disease. Six patients of group A and no patient of group B underwent
      colectomy. The histological evaluation showed an increased thickness of the
      entire colonic wall with significant changes of the perivisceral fat structures.
      CONCLUSIONS: An increased

PMID- 11232695
TI  - Hemostatic imbalance in active and quiescent ulcerative colitis.
AB  - OBJECTIVE: In healthy conditions, factors inducing or inhibiting coagulation and
      factors inducing or inhibiting fibrinolysis are in balance. In ulcerative
      colitis, hypercoagulation is presumed, which may explain part of the clinical
      features of this disease. Therapy strategies affecting hemostasis may improve the
      course of ulcerative colitis. This study was conducted to evaluate the balance of
      coagulation and fibrinolysis in the course of treatment of active ulcerative
      colitis. METHODS: Patients with active ulcerative colitis were studied by serial
      determination of markers of the coagulation cascade (thrombin-antithrombin
      complexes and fibrin degradation products [FbDP]) and the fibrinolytic cascade
      (fibrinogen degradation products [FgDP]). Parameters of inflammation were also
      measured (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR],
      albumin, platelet count, and fibrinogen). Disease activity was assessed by
      endoscopic and histopathological scores. Follow-up measurement was performed in
      the course of treatment at the third or fourth month after baseline. Measurements
      were compared with healthy controls. RESULTS: Thirty-three patients and 22
      healthy controls were included. During active ulcerative colitis, inflammatory
      parameters (CRP, ESR, platelet count) and hemostatic parameters (thrombin
      antithrombin complexes, fibrinogen, FgDP, and FbDP) were elevated in comparison
      with healthy controls. Albumin was decreased and antithrombin-III remained
      unchanged. During treatment, disease activity decreased significantly
      endoscopically and histopathologically (p < 0.001). CRP, ESR, platelet count, and
      fibrinogen also decreased significantly. The hemostatic balance, expressed as the
      ratio between the plasmin-dependent generation of FgDP and coagulation-dependent
      generation of FbDP, increased from 0.69 to 1.12 during treatment, mainly because
      of a decrease of FbDP. In healthy controls, this ratio was CONCLUSIONS: The
      coagulation and fibrinolytic cascades were activated in active ulcerative
      colitis, with a hemostatic imbalance in favor of coagulation. This
      hypercoagulability persisted in 20% (7/33) of patients with ulcerative colitis in
      remission. The decrease of FbDP and the increase in the FgDP/FbDP ratio during
      reconvalescence of ulcerative colitis showed that the coagulation cascade was
      more activated than the fibrinolytic cascade in active disease.

PMID- 11232696
TI  - Small intestinal mucosal immunity and morphometry in luminal overgrowth of
      indigenous gut flora.
AB  - OBJECTIVE: The aim of this study was to investigate the separate effects of
      indigenous oropharyngeal- and colonic-type flora on small intestinal mucosal
      immunity and morphometry in small intestinal bacterial overgrowth (SIBO).
      METHODS: A duodenal aspirate and random biopsies of underlying mucosa were
      obtained from 52 adult subjects (age range, 18-90 yr; median, 60 yr) without
      disorders that may otherwise disturb small intestinal histology or mucosal
      immunity. Villus height, crypt depth, villus/crypt ratios, counts of
      intraepithelial lymphocytes (IELs) and lamina propria total mononuclear cells,
      IgA, IgM, and IgG plasma cells, mast cells, and B and T lymphocytes were
      determined in relation to the presence or absence of SIBO and the nature of the
      overgrowth flora in all subjects. CD4+ve and CD8+ve T-cell counts were determined
      in 24 subjects. RESULTS: SIBO was present in 26 of 52 (50%) subjects. Overgrowth
      flora included colonic-type bacteria in 20 subjects and oropharyngeal-type flora
      alone in 6 subjects. Lamina propria IgA plasma cell counts were significantly
      increased in subjects with SIBO, irrespective of whether the overgrowth flora
      comprised oropharyngeal-type flora alone or included colonic-type bacteria.
      Neither villus height, crypt depth, villus/crypt ratios, nor total or other
      mononuclear cell counts in lamina propria differed significantly between subjects
      with and without SIBO, irrespective of the nature of the overgrowth flora. IEL
      counts were significantly higher than in culture-negative subjects only when the
      overgrowth flora included colonic-type bacteria. Even then, IEL counts were
      within a range currently considered normal. A significant, inverse correlation
      between advancing age and IEL counts became apparent after adjusting for the
      effect of SIBO of colonic-type flora. CONCLUSIONS: SIBO of oropharyngeal- and
      colonic-type flora are associated with differing disturbances of local duodenal
      mucosa. Nonetheless, these would not be readily apparent during routine
      histological assessment. Old age independently influences duodenal IEL counts.

PMID- 11232697
TI  - Low mortality in ulcerative colitis and Crohn's disease in three regional centers
      in England.
AB  - OBJECTIVES: Recent epidemiological studies suggest that mortality rates for
      inflammatory bowel disease (IBD) are similar to those of the general population.
      However, most of this work has been done in referred populations or larger urban
      centers. We intended to estimate mortality rates for ulcerative colitis (UC) and
      Crohn's disease (CD) in three British district general hospital practices in
      Wolverhampton, Salisbury, and Swindon. METHODS: Consecutive patients with CD or
      UC were identified from 1978 to 1986 and followed prospectively. Demographic
      data, date and cause of death or health status at December 31, 1993 were used to
      estimate standardized mortality ratios (SMRs) and 95% confidence intervals.
      RESULTS: Sixty-four deaths occurred in 552 patients (UC 41 of 356; CD 23 of 196).
      The overall SMRs were 103 [95% confidence interval (CI): 79-140] for UC and 94
      (95% CI: 59-140) for CD. The respective SMRs were higher only in the first year
      after diagnosis at 223 (95% CI: 99-439; p = 0.02) and 229 (74-535; p = 0.056),
      and even then, most subjects died from non-IBD causes (5 of 13). Nonsurvivors
      were significantly older than survivors in both UC and CD (p < 0.01). The SMR was
      also significantly greater during a severe first attack of UC at 310 (95% CI: 84
      793; p = 0.04). Patients with perianal or colonic CD had an increased SMR [396
      (95% CI: 108-335; p = 0.02) and 164 (95% CI: 82-335; p = 0.02)] respectively,
      partly related to the older mean age (52 vs 32 yr, p < 0.001). CONCLUSIONS:
      Mortality rates are not increased in IBD compared with the general population.
      However, older patients may be at increased risk of dying from other causes early
      in the disease clinical course.

PMID- 11232698
TI  - Immunoglobulin E and eosinophilic cationic protein in segmental lavage fluid of
      the small and large bowel identify patients with food allergy.
AB  - OBJECTIVE: Members of the general population often assume that they suffer from
      food allergy, but the true prevalence is low. Testing for the diagnosis of food
      related hypersensitivity entails laborious procedures, including GI endoscopy.
      Our objective was to develop an endoscopic screening approach for food allergy.
      METHODS: Endoscopically guided segmental lavage was performed in 11 patients with
      GI allergy and in 20 controls during lower GI endoscopy of the terminal ileum,
      the coecum, and the rectosigmoid. Eosinophilic cationic protein (ECP) and protein
      were measured in native lavage fluid, and immunoglobulin E (IgE) was also
      measured after a 10-fold lavage concentration. RESULTS: IgE/protein in lavage
      fluid from the coecum (0.055 +/- 0.068 U/mg vs 0.003 +/- 0.012 U/mg; p = 0.001)
      and the rectosigmoid (0.134 +/- 0.170 U/mg vs 0.019 +/- 0.042 U/mg; p < 0.05) was
      significantly elevated in patients with GI allergy. ECP/protein was significantly
      elevated at the terminal ileum (22.95 +/- 37.67 microg/mg vs 7.09 +/- 7.68
      microg/mg; p < 0.05) and the rectosigmoid (23.66 +/- 19.43 microg/mg vs 11.97 +/-
      16.39 microg/mg; p < 0.05). The combined use of GI lavage IgE and ECP as a
      diagnostic test for food allergy resulted in a sensitivity of 91% and a
      specificity of 80%. CONCLUSIONS: In endoscopically guided segmental lavage fluid,
      IgE and ECP/protein are increased in patients with food allergy. These
      measurements seem to offer an attractive diagnostic tool and may serve as a
      screening method.

PMID- 11232699
TI  - Focal neurological signs in hepatic encephalopathy in cirrhotic patients: an
      underestimated entity?
AB  - OBJECTIVES: Focal neurological signs have been poorly documented in the course of
      hepatic encephalopathy in cirrhotic patients because they are not mentioned in
      any textbooks of liver diseases. Having the opportunity to observe such cases, we
      underwent a prospective study to determine incidence, characteristics, associated
      factors, prognostic significance, and outcome of this rare form of hepatic
      encephalopathy. METHODS: Over a 12-month period, all cirrhotic patients
      hospitalized in the intensive care unit of our department for hepatic
      encephalopathy were prospectively studied. Patients with clinical and
      electroencephalogram evidences of hepatic encephalopathy were examined by a
      senior physician and, in cases of focal neurological signs, underwent examination
      by a neurologist, CT scan, lumbar punction, and cerebral magnetic resonance
      imaging and echo Doppler examination of neck and head vessels. Clinical and
      biological parameters were compared in patients during episodes with and without
      focal neurological signs, and outcome was noted. RESULTS: Thirty-four cirrhotic
      patients were hospitalized for 48 episodes of hepatic encephalopathy; two of
      these patients with cerebral hematoma were excluded. Twenty-four patients
      exhibited 38 hepatic encephalopathy episodes without focal neurological signs
      (82.6%), and eight patients exhibited eight hepatic encephalopathy episodes with
      focal neurological signs (17.4%) that were hemiplegia and hemiparesia in six
      patients (75%). In all patients, cerebral CT scan and cerebrospinal fluid
      examination disclosed no abnormalities, as neither did cerebral magnetic
      resonance imaging (n = 5) and echo Doppler examination of neck and head vessels
      (n = 5). Except for female sex, which was more often encountered in patients with
      focal neurological signs (p < 0.05), there were no differences between episodes
      with and without focal neurological signs for any of the parameters studied. In
      surviving patients who recovered from hepatic encephalopathy (7/8), focal
      neurological signs disappeared without recurrences after follow up of 6 months (3
      12). CONCLUSIONS: Hepatic encephalopathy with focal neurological signs when
      carefully searched is not uncommon. It could be more frequent in cirrhotic
      females, is reversible, and has no prognostic significance.

PMID- 11232700
TI  - A pilot study of a thiazolidinedione, troglitazone, in nonalcoholic
      steatohepatitis.
AB  - OBJECTIVES: Troglitazone is a thiazolidinedione and peroxisome proliferator
      activated receptor gamma (PPARgamma) ligand used to treat diabetes mellitus type
      II. Because hyperinsulinemia may be a factor in nonalcoholic steatohepatitis
      (NASH), we postulated that troglitazone could have beneficial effects in this
      disorder. Our study was initiated before reports of idiosyncratic hepatitis
      induced by this agent and was completed before its recent withdrawal from the
      market. METHODS: We studied 10 female patients (age 44 +/- 16) with histological
      NASH. All but two were obese (mean body mass index, BMI = 38 +/- 6). One had type
      2 diabetes, and three had well-compensated cirrhosis with NASH. Troglitazone was
      given at a dose of 400 mg/day for < or = 6 months. Responders (defined as normal
      ALT at the end of treatment) were rebiopsied. Paired specimens were compared in
      blinded fashion. Mitochondria were quantitated using ultrathin electron
      microscopy. RESULTS: Seven of ten patients responded with normal ALT at the end
      of treatment. One of three nonresponders initially normalized ALT but returned to
      pretreatment level at 3 months. In this patient, therapy was stopped, and the ALT
      has remained at the baseline level with no other clinical or laboratory findings.
      In the responders, ALT fell from 87 +/- 38 before to 39 +/- 9 at the end of
      treatment (p = 0.01), and AST decreased from 77 +/- 23 to 30 +/- 8 (p = 0.002).
      Biopsy comparisons before and after therapy showed persistent steatohepatitis in
      all cases, although four of seven showed a one-point improvement in the
      necroinflammatory grade. Electron microscopy revealed elongation of the
      mitochondria after therapy. CONCLUSIONS: Normal ALT was seen in 70% of NASH
      patients at the end of treatment, but this biochemical response was associated
      with only mild histological improvement, and all follow-up biopsies had evidence
      of NASH. Normalization of the liver enzymes in patients with NASH who are treated
      with thiazolidinediones should be viewed with reservation. Follow-up biopsy is
      essential to evaluate the efficacy of these agents, which, at the histological
      level, appears to be relatively modest.

PMID- 11232701
TI  - Famciclovir treatment in transplant recipients with HBV-related liver disease:
      disappointing results.
AB  - OBJECTIVE: Long-term administration of hepatitis B immune globulin is effective
      as prophylaxis for hepatitis B virus (HBV) reinfection but is limited by cost,
      side effects, availability and a failure rate of 20%. Famciclovir has been shown
      to be effective in the treatment of hepatitis B in the immunocompetent patient.
      Fewer data exist in the liver transplant setting, particularly regarding its
      efficacy in de novo HBV infection. The aims of this pilot study were to determine
      the effectiveness and safety of long-term administration of famciclovir in
      recurrent (n = 3) and de novo (n = 3) HBV infection after liver transplantation.
      METHODS: Six patients with postransplant HBV infection (positivity of serum HBsAg
      and HBV DNA), four of whom were HBeAg positive, were treated with famciclovir
      (500 mg, 3 times a day) with a minimum follow-up period of 12 months.
      Biochemical, serological, virological (HBV DNA by hybridization assays and
      polymerase chain reaction), and histological (including HBV immunostaining)
      endpoints were evaluated. RESULTS: None of the patients had a complete
      biochemical response, with a near complete normalization of ALT levels being
      observed in 3/6 patients. There was a lack of correlation between virological and
      biochemical responses. None of the patients seroconverted to anti-HBs or anti
      HBe. A virological clearance was observed in only two patients, whereas a
      moderate reduction in HBV DNA levels was present in one. HBV DNA levels were
      higher than levels during pretreatment in the three remaining patients.
      Histological improvement was only observed in one patient. CONCLUSION:
      Famciclovir alone appears of limited efficacy in the treatment of HBV infection
      after liver transplantation.

PMID- 11232702
TI  - The natural history of hepatitis D virus infection in Illinois state facilities
      for the developmentally disabled.
AB  - OBJECTIVE: We sought to define the natural history of hepatitis D virus infection
      in an institutionalized, developmentally disabled population and to identify
      other prognostic factors. METHODS: A retrospective cohort study was conducted on
      231 hepatitis B virus carriers, 65 of whom were also infected with hepatitis D
      virus, at thirteen Illinois state facilities for the developmentally disabled.
      Demographic, clinical and laboratory data from 1986 to 1998 were obtained by
      chart review. Cox regression analysis was used to compare those with and without
      hepatitis D virus infection in terms of overall mortality, mortality from hepatic
      disease, and risk of developing chronic hepatitis and cirrhosis and to identify
      other potential prognostic factors. RESULTS: Residents with hepatitis D virus
      infection were more likely to die of liver disease than uninfected residents (11%
      vs 0.6%, respectively; relative hazard, 15.2; 95% confidence interval, 1.8
      126.6), although there was no significant difference in overall mortality. Twenty
      one percent of residents with hepatitis D virus infection were diagnosed to have
      cirrhosis or chronic hepatitis compared with 9% of those uninfected (relative
      hazard 2.5, 95% confidence interval 1.2-5.2). Among the other variables tested,
      none was predictive of risk of dying of liver disease, and only seropositivity
      for hepatitis B e antigen was predictive of risk of developing cirrhosis or
      chronic hepatitis. CONCLUSIONS: In an institutionalized, developmentally disabled
      population of hepatitis B virus carriers, hepatitis D virus infection is
      associated with a greater risk of liver-associated mortality and of developing
      chronic liver disease than that associated with hepatitis B virus carriage alone.

PMID- 11232703
TI  - Functional hepatic volume measured by technetium-99m-galactosyl-human serum
      albumin liver scintigraphy: comparison between hepatocyte volume and liver volume
      by computed tomography.
AB  - OBJECTIVES: We investigated the usefulness of measuring the functional hepatic
      volume by single-photon emission CT with 99m-technetium galactosyl-human serum
      albumin scintigraphy (GSA-LV). We then compared this value to the total
      hepatocyte volume and the hepatic volume determined from CT (CT-LV) in the
      patients with hepatobiliary tumors. METHODS: Forty-seven patients were divided
      into two groups, the SM group (subsegmentectomy and monosegmentectomy) and the DT
      group (disegmentectomy and trisegmentectomy). These groups were further divided
      into subgroups with or without chronic hepatitis or cirrhosis. The GSA-LV, CT-LV,
      and the total hepatocyte volume were then calculated. The GSA-LV and CT-LV
      measurements were performed preoperatively, at 2 and 4 wk, and at 3 and 6 months
      after surgery. RESULTS: The preoperative GSA-LV values were significantly
      correlated with the hepatocyte volume and the 15-min retention rate of
      indocyanine green (ICGR15). Similarly, the hepatocyte volume correlated well with
      the CT-LV and ICGR15. However, the CT-LV was correlated only with the ICGR15.
      Recovery of the GSA-LV in the DT group was delayed, and about 90% of the
      volumetric and functional regeneration was observed within 6 months after the
      hepatectomy. In contrast, the CT-LV of DT group patients with normal liver
      remnants returned to approximately 90% of their initial volume within 1 month
      after the hepatectomy, whereas patients with injured livers regenerated gradually
      and regained approximately 80% of their preoperative value by 6 months after the
      hepatectomy. CONCLUSIONS: We conclude that the measurement of functional hepatic
      volume using the GSA-LV is useful in fully evaluating hepatic function based on
      hepatocyte volume.

PMID- 11232704
TI  - Can one predict when ultrasound will be useful with percutaneous liver biopsy?
AB  - OBJECTIVE: We previously showed that ultrasound altered position of biopsy in 15%
      of cases by demonstrating intervening structures. This study was designed to test
      whether one could predict in which cases ultrasound would be useful. METHODS: A
      standard percussion technique was used. The site chosen was marked. Criteria were
      established to indicate whether a move might be predicted to be likely. If 10 or
      more points were assigned, then it was predicted that ultrasound would change
      position. A difficult percussion was assigned 10 points; obesity, 5 points; and
      chest deformity, 5 points. The ultrasound was then applied to the marked spot in
      every case. If an intervening structure was present within 6 cm, the biopsy site
      was moved. Otherwise, the biopsy was taken from the marked site. RESULTS: One
      hundred seventeen consecutive liver biopsies were included between January 1999
      and January 2000. The criteria predicted the desirability of nine moves. No moves
      were made, however, in these cases. In 17 cases (14.5%), moves were made because
      of intervening structures. None of the cases were predicted. A move was made in 1
      of 23 obese patients. There was no statistical difference in moves made between
      obese and nonobese patients. CONCLUSIONS: Using criteria of difficult percussion,
      obesity, and unusual chest shape, we could not predict when ultrasound would be
      useful. This is in contrast to the belief that ultrasound can be applied to
      selected liver biopsies considered in advance to be more difficult, as in the
      obese patients, and instead suggests that to avoid intervening structures, one
      should apply ultrasound to all cases.

PMID- 11232705
TI  - Influence of esophageal varices and spontaneous portal-systemic shunts on
      postprandial splanchnic hemodynamics.
AB  - OBJECTIVE: The aim of the study was to assess postprandial splanchnic hemodynamic
      changes in cirrhosis in relation to variceal status. METHODS: In 9 healthy
      controls and 56 patients with liver cirrhosis, stratified according to variceal
      status and presence of spontaneous portal-systemic shunts, the portal vein
      diameter and flow velocity, the congestion index of the portal vein, and the
      resistive index of the superior mesenteric artery (SMA-RI) were studied by
      Doppler ultrasound before and 30, 60, and 120 min after the intake of a standard
      meal. Comparison of postprandial parameters with basal ones was done within each
      group by paired t test and among groups by ANOVA and Duncan test. RESULTS:
      Healthy controls and cirrhotic patients without varices showed similar
      significant splanchnic hemodynamic changes, namely a reduction of SMA-RI (-13% at
      30 min) and a consequent increase in portal vein diameter (respectively, +32% and
      +17% in the two groups) and velocity (+66% and +51%). A significant reduction of
      SMA-RI was also found in patients with varices, irrespective of the variceal size
      (range, -7 to -11%), but the expected portal vein dilation and velocity increase
      were progressively blunted with the increase of variceal size (range, 0-5% for
      diameter and 5-19% for velocity). Patients with spontaneous portal-systemic
      shunts showed a response similar to that of patients with large varices.
      Significant modification of the congestion index of the portal vein did not occur
      in any group. CONCLUSIONS: Our results show that the hemodynamic response to meal
      in patients with liver cirrhosis is influenced by the presence and size of
      esophageal varices and the presence of spontaneous portal-systemic shunts.

PMID- 11232706
TI  - Lamivudine therapy for spontaneously occurring severe acute exacerbation in
      chronic hepatitis B virus infection: a preliminary study.
AB  - OBJECTIVE: The nucleoside analogue lamivudine, a potent inhibitor of hepatitis B
      virus replication, has shown notable results in treating chronic hepatitis B.
      However, lamivudine has not been specifically tested for effectiveness against
      spontaneously occurring severe acute exacerbations of hepatitis in patients
      chronically infected with this virus. We addressed this issue in a pilot study.
      METHODS: Ten patients with chronic hepatitis B developed severe acute
      exacerbation spontaneously during follow-up; 3 of them developed hepatic failure
      shortly before entering the trial. Lamivudine was administered long-term to the
      10 patients at a daily oral dose of 100 or 300 mg. RESULTS: All 3 patients with
      hepatic failure at initiation of treatment recovered dramatically. Of the
      remaining 7 patients, 5 recovered rapidly with lamivudine, but 2 progressed
      quickly to hepatic failure despite treatment. One died of sepsis and the other of
      multiorgan failure. In the 8 survivors, serum alanine transaminase activity
      decreased rapidly to normal with lamivudine therapy, and serum hepatitis B virus
      DNA level declined rapidly to undetectable levels. Serum total bilirubin
      concentrations normalized somewhat later. Prothrombin time improved steadily and
      gradually. Hepatitis B e antigen elimination or seroconversion was achieved in 3
      survivors. No adverse effects were noted in any patient. All survivors had good
      quality of life with long-term lamivudine monotherapy. CONCLUSIONS: Lamivudine is
      effective, safe, and well tolerated by patients with spontaneous, severe, acute
      exacerbation complicating chronic hepatitis B virus infection, even in the
      presence of hepatic failure. Lamivudine appears to be an attractive therapeutic
      option and may represent the best choice.

PMID- 11232707
TI  - Human toxocariasis and pyogenic liver abscess: a possible association.
AB  - OBJECTIVES: To study the role of human toxocariasis in the pathogenesis of
      pyogenic liver abscess. METHODS: We compared the serology for toxocariasis and
      serum levels of IgE in 16 patients with pyogenic liver abscess to those in 32
      matched (age and gender) controls to define the possible association between
      these two entities. RESULTS: The serology for toxocariasis was positive in 10 of
      16 patients compared with 4 of 32 controls. The relative odds and 95% confidence
      interval (conditional logistic regression), comparing cases and matched controls,
      was significant (1.4; 95% confidence interval, 1.1-1.7) for Toxocara serology.
      Regarding IgE serum levels, there was no difference between cases and controls.
      CONCLUSIONS: Human toxocariasis can be one of the predisposing causes of pyogenic
      liver abscess, especially in tropical countries in which this parasitic disease
      is common. Treatment of human toxocariasis may prevent morbid complications like
      hepatic abscess and should be considered in patients with clinical and/or
      serological evidence of Toxocara infection.

PMID- 11232708
TI  - Is there a threshold of hepatic iron concentration that leads to cirrhosis in
      C282Y hemochromatosis?
AB  - OBJECTIVE: The relationship between the degree of iron overload and the presence
      of cirrhosis has not been clearly established in hemochromatosis. Severe iron
      overload occurs without cirrhosis and moderate iron overload can occur with
      cirrhosis. Previous estimates may have overestimated the problem because of the
      overdiagnosis of hemochromatosis in patients with alcoholic liver disease and
      chronic viral hepatitis. The objective of this study was to determine if a
      threshold for hepatic iron concentration leads to the development of cirrhosis in
      C282Y hemochromatosis. METHODS: This study included only hemochromatosis patients
      who were homozygotes for the C282Y mutation of the HFE gene and had undergone
      liver biopsy with hepatic iron concentration. Analysis of the thresholds for
      cirrhosis were determined using receiver operating characteristic (ROC) curve
      analysis. RESULTS: Data were available on 100 C282Y homozygotes (62 men, 38
      women; mean age 51, range 18-74 yr). ROC curve analysis showed an area under the
      curve for hepatic iron concentration versus cirrhosis of 0.85 (95% CI = 0.75
      0.96). The threshold for the prediction of cirrhosis was 283 micromol/g. At that
      threshold, the sensitivity was 85% and specificity 84%. CONCLUSIONS: From this
      analysis, it appears that a hepatic iron concentration >283 micromol/g is
      associated with cirrhosis. However, the low sensitivity of this threshold
      suggests that other cofactors contribute to the development of cirrhosis in
      hemochromatosis. Early diagnosis is encouraged to initiate iron depletion before
      the development of cirrhosis.

PMID- 11232709
TI  - The nature of after-hours telephone medical practice by GI fellows.
AB  - OBJECTIVE: Gastroenterology fellows on-call often serve as the initial or only
      contact for patients calling "after hours" with questions and symptoms. These
      fellows are rarely trained specifically in how to handle these calls. The aim of
      this study was to determine whether there are particular topics in telephone
      medicine that ought to be covered in new fellow training. Therefore, we sought to
      evaluate the nature of after-hours pages initiated by patients and to document
      the advice given by fellows. METHODS: The content of 100 patient-initiated
      telephone calls with GI fellows was recorded prospectively over 7 months. We
      included pages received between 5 PM and 8 AM daily as well as daytime calls on
      weekends. Fellows documented the time and length of the call, the issue raised by
      the patient, the advice given, and the patient's gender and attending
      gastroenterologist. When a particular patient paged more than once in a 24-h
      period, the repeat calls were not counted toward the 100-call tally. RESULTS:
      Twenty-two percent of calls occurred between 11 PM and 7 AM. Eighty-three percent
      of calls lasted less than 10 min. Sixty-seven percent of patients called because
      of symptoms. Only 30% of patients calling with symptoms were referred to the
      emergency room. Although only 1 of 13 patients with procedure-related (i.e.,
      postendoscopy) symptoms required admission to the hospital, 18 of 54 (33%)
      patients with nonprocedure-related symptoms required admission either immediately
      or within a month of calling after hours. CONCLUSIONS: Most after-hours calls
      from patients are related to symptoms. Patients calling with postprocedure
      symptoms rarely require admission to the hospital. Conversely, a significant
      number of patients calling with non-procedure-related symptoms require admission
      within 30 days. Fellowship directors should consider providing training to
      fellows in the evaluation of symptoms over the telephone.

PMID- 11232710
TI  - Prognostic significance of natural killer cell activity in patients with gastric
      carcinoma: a multivariate analysis.
AB  - OBJECTIVE: Natural cytotoxicity, mediated by natural killer (NK) cells, has been
      believed to play an important role in inhibiting experimental tumor metastasis,
      and diminished NK cell activities leads to a high incidence of tumor occurrence.
      Despite convincing evidence from experimental studies, the role of NK cells in
      the immunological surveillance against cancer in human is poorly defined.
      METHODS: The present study was based on a retrospective analysis of data on 156
      patients with gastric cancer, who were surgically treated in the Department of
      Surgery II, Kyushu University Hospital from 1993 to 1996. All patients were
      examined for NK cell activity based on a peripheral blood sampling done
      preoperatively. RESULTS: Significant association between NK cell activity and
      clinicopathological parameters including tumor size, lymphatic involvement,
      vascular involvement, and lymph node metastases was evident. When comparing the
      two groups according to NK cell activity, tumors with low NK cell activity tend
      to have lymphatic involvement. The 5-yr survival rates were 94.6% and 72.3% for
      those with NK cell activity > 25% lysis and < or = 25% lysis, respectively, the
      value being statistically significant (p < 0.05). The independent risk factors
      for prognosis examined by logistic regression analysis were lymphatic
      involvement. NK cell activity, depth of tumor invasion, and lymph node
      dissection. CONCLUSIONS: These current data showed that NK cell activity may be
      related to tumor volume and dissemination. Measurement of preoperative NK cell
      activity may be pertinent for the prognosis of patients with gastric cancer and
      for follow-up clinical management.

PMID- 11232711
TI  - Assessment of utilities and health-related quality of life in patients with
      chronic liver disease.
AB  - OBJECTIVES: Quantitative measures of the value patients place on the state of
      their health is crucial to understanding their experience, and to calculate
      quality-adjusted years of life for economic analyses. Patients' values in chronic
      liver disease remain unexplored, although experts' estimates of utilities have
      been examined. Our study tests the validity of a widely used utility measure in
      chronic liver disease and, if valid, establishes the decrement in health-related
      quality associated with chronic liver disease. METHODS: A total of 120 patients
      with chronic liver disease participated in the study (age 50 +/- 10 yr; men 53%;
      cirrhosis 51%, chronic viral hepatitis 51%, and chronic cholestatic liver disease
      30%). All patients completed three instruments: Health Utility Index Mark 2
      (scores 0-1), Short Form-36 (scale scores 0-100), and a disease-specific health
      related quality of life instrument (Chronic Liver Disease Questionnaire; scores 1
      7). RESULTS: We found a moderate to strong correlation between scores on the
      three measures and that impairment worsened as the severity of disease worsened.
      Patients without cirrhosis and those with Child's A cirrhosis showed substantial
      decrement in utilities (0.82 and 0.83, respectively) in the range of patients
      surviving brain tumor. Those with Child's B and C showed a greater decrement
      (0.67 and 0.56) that was in the range experienced by patients who survive a
      stroke (0.67). Utilities assessed by Health Utility Index Mark 2 differed
      substantially from estimates by "expert." CONCLUSIONS: We conclude that utilities
      should be based on patient reports and that the data from this study can inform
      economic analyses in studies of patients with chronic liver disease.

PMID- 11232712
TI  - Magnetoelectric machine.

PMID- 11232713
TI  - Consecutive occurrence of primary biliary cirrhosis and autoimmune hepatitis: a
      case report and review of the literature.
AB  - Autoimmune cholangiopathy is a term that describes a subset of patients with
      overlapping features of primary biliary cirrhosis (PBC) and autoimmune hepatitis
      (AH). These patients typically have cholestasis, negative antimitochondrial
      antibody (AMA), liver histology suggestive of PBC, and may respond clinically to
      corticosteroid therapy. We describe a patient who presented with typical AMA
      positive, biopsy-proven PBC who responded to ursodeoxycholic acid therapy both
      clinically and biochemically. Approximately 3 yr later, she developed elevated
      transaminases with biopsy-proven antinuclear antibody (ANA) negative AH. The AMA
      was negative at this time. After responding to steroid therapy for the AH and
      after discontinuing the ursodeoxycholic acid, the patient had a clinical
      recurrence of PBC with renewed AMA positivity.

PMID- 11232714
TI  - Chronic graft-versus-host disease after hematopoietic cell transplantation
      presenting as an acute hepatitis.
AB  - A variety of illnesses involving the gut and liver follow hematopoietic cell
      transplantation (HCT). A 20 yr-old white male developed severe acute hepatitis 36
      wk (day 252) after matched, unrelated, allogeneic HCT for chronic myelogenous
      leukemia (CML). Mild skin graft-versus-host disease (GVHD) had occurred at about
      20 wk (day 140) after transplant. Liver biopsy showed bile duct injury and a
      diffuse lobular injury pattern most consistent with a GVHD variant and not
      reminiscent of drug-induced or viral hepatitis. No findings suggestive of
      herpesvirus, adenovirus, or varicella-zoster virus were found. High-dose steroids
      resulted in marked improvement of his liver enzyme levels. We report this patient
      as representing the acute hepatitic presentation of chronic GVHD of the liver.

PMID- 11232715
TI  - Chronic pancreatitis and aortic pseudoaneurysm in Behcet's disease.
AB  - Behcet's disease is a chronic, recurrent, systemic disease characterized by
      orogenital ulcers and oculocutaneous inflammatory lesions. Cardiovascular,
      pulmonary, neurological, articular, and GI involvement are common features, but
      pancreatic involvement is very rare. We present a case of Behcet's disease with
      both chronic pancreatitis and abdominal aorta pseudoaneurysm.

PMID- 11232716
TI  - Recurrent ulcer bleeding: is intravenous omeprazole the solution?

PMID- 11232717
TI  - EUS to the rescue?

PMID- 11232718
TI  - Re: Irwin editorial--cough in GERD.

PMID- 11232719
TI  - Cholestyramine for treatment of chronic diarrhea.

PMID- 11232720
TI  - Habba et al.: chronic diarrhea--identifying a new syndrome.

PMID- 11232721
TI  - Re: Ammonia cannot explain the effect of H. pylori on omeprazole-induced acid
      suppression.

PMID- 11232722
TI  - Diabetic ketoacidosis induced by alpha interferon and ribavirin treatment in a
      patient with hepatitis C.

PMID- 11232723
TI  - H. pylori and gastroplasty in the treatment of morbid obesity.

PMID- 11232724
TI  - Reactivation of hepatitis B virus infection during cytotoxic chemotherapy.

PMID- 11232725
TI  - Interferon and ribavirin treatment for chronic hepatitis C may activate celiac
      disease.

PMID- 11232726
TI  - Recidivant midgut neuroendocrine tumor in a celiac patient.

PMID- 11232728
TI  - The effect of ursodeoxycholic acid in children with prolonged hepatitis A virus
      infection that may be a trigger factor for autoimmune hepatitis.

PMID- 11232727
TI  - Portal venous gas associated with nonocclusive mesenteric infarction.

PMID- 11232729
TI  - A resected case of adenolipoma of the colon: is it a new entity of the colonic
      tumor?

PMID- 11232730
TI  - Sustained remission of chronic hepatitis C after a change to human leukocyte
      interferon-alpha in a difficult-to-treat patient with breakthrough phenomenon
      associated with antibodies against recombinant interferon-alpha.

PMID- 11232731
TI  - Re: Ockenga et al.--mutations of cystic fibrosis gene in patients with
      pancreatitis.

PMID- 11232732
TI  - Coexistence of a granulocytic sarcoma and adenocarcinoma of the rectum.

PMID- 11232733
TI  - Azathioprine-induced destructive cholangitis.

PMID- 11232734
TI  - Increased number of CD5+ and CD20+ B-lymphocyte subpopulation in gastroenterology
      endoscopy staff.

PMID- 11232735
TI  - Acute exacerbations of chronic bronchitis: what role for the new
      fluoroquinolones?
AB  - Acute exacerbations of chronic bronchitis (AECB) are a major cause of morbidity
      and mortality. Bacterial pathogens are implicated in about half the episodes of
      AECB. Empirical antibacterials have a significant benefit in AECB; however,
      several recent developments have considerably complicated antibacterial choice
      for this condition. New fluoroquinolone antibacterials introduced in the last
      decade are theoretically well suited for the treatment of AECB, as the in vitro
      antimicrobial spectrum of these drugs includes all the major pathogens involved.
      The pharmacokinetic and pharmacodynamic properties of the new fluoroquinolones
      are superior to many other antibacterials used to treat AECB. In trials, clinical
      success with the new fluoroquinolones was equivalent and bacteriological success
      was occasionally superior to nonfluoroquinolone comparators. However, these
      clinical trials did not assess several potentially important end-points for which
      the theoretical superiority of the fluoroquinolones may translate into
      differences in outcome. Rare but serious adverse effects with some of the new
      fluoroquinolones have shaken the confidence of prescribing physicians in this
      class of drugs. Emergence of the resistance of Streptococcus pneumoniae to
      fluoroquinolones has raised concerns about indiscriminate and widespread use of
      the new agents for trivial infections. Patients with AECB are a heterogeneous
      population who should be stratified in order to appropriately choose empirical
      antibacterial therapy. Highly efficacious antibacterial therapy, such as the new
      fluoroquinolones, is appropriate as a first-line choice for patients who have
      risk factors for a poor outcome or are in intensive care units. Such selected use
      of the new fluoroquinolones balances individual benefit with societal concerns of
      the use of these agents for AECB.

PMID- 11232737
TI  - Management of type 2 diabetes mellitus in the elderly: special considerations.
AB  - The principles of managing type 2 diabetes mellitus in the elderly are no
      different from those in younger patients, but the priorities and therapeutic
      strategies need to be cautiously individualised. The objectives of treatment are
      to improve glycaemic control in a stepwise approach that involves
      nonpharmacological methods including diet and exercise, and pharmacological
      therapy including mixtures of oral antihyperglycaemic agents alone or in
      combination with insulin. Although the goals of treatment may be the same for
      elderly and younger patients, certain aspects of type 2 diabetes in the elderly
      require special consideration. Treatment decisions are influenced by age and life
      expectancy, comorbid conditions and severity of the vascular complications.
      Adherence to dietary therapy, physical activity, and medication regimens may be
      compromised by comorbid conditions and psychosocial limitations. Drug-induced
      hypoglycaemia has been the main consideration and the most serious potential
      complication. In addition, the long term macrovascular and microvascular
      complications of type 2 diabetes are a source of significant morbidity and
      mortality. Indeed, vascular and neuropathic complications are already present at
      the time of diagnosis in a significant number of patients, and the impact of
      improved diabetes control depends on the age and life expectancy of the patient.
      Age-related changes in pharmacokinetics and the potential for adverse effects and
      drug interactions should also be considered when choosing appropriate
      pharmacological therapy. In general, a conservative and stepwise approach to the
      treatment of the elderly patient with type 2 diabetes is suggested; treatment may
      be initiated with monotherapy, followed by early intervention with a combination
      of oral agents including a sulphonylurea as a foundation insulin secretagogue in
      addition to a supplemental insulin sensitiser. Insulin therapy is eventually
      required if significant hyperglycaemia [glycosylated haemoglobin (HbA1c) >8%]
      persists despite oral combination therapy. Combination therapy with evening
      insulin and a long-acting sulphonylurea such as glimepiride is an effective
      strategy to improve hyperglycaemia in the elderly patient with type 2 diabetes in
      whom polypharmacy with oral agents is unsuccessful. In addition, such a regimen
      is simple to follow for the patient who may not be able to adhere to a more
      complicated insulin regimen. Hyperglycaemia in the elderly can be managed well
      with practical intervention and a straightforward treatment plan to enhance
      compliance. Optimal glycaemic control should be possible for every patient if
      treatment is individualised; however, strict glycaemic control may not be
      achievable in all patients or even desirable in many elderly patients.

PMID- 11232736
TI  - Pain in nursing home residents: management strategies.
AB  - Pain is prevalent and undertreated in nursing home residents, despite the
      existing wide array of effective pharmacological and nonpharmacological treatment
      modalities. In order to improve the quality of life of these vulnerable
      individuals, practitioners require education about the correct approach to
      assessment and management. Assessment should be comprehensive, taking into
      account the basic underlying pathology (e.g. osteoarthritis, osteoporosis,
      peripheral neuropathy, fibromyalgia, cancer) as well as other contributory
      pathology (e.g. muscle spasm, myofascial pain) and modifying comorbidities (e.g.
      depression, anxiety, fear, sleep disturbance). Pharmacological management should
      be guided by a stepped-care approach, modelled after that recommended by the
      World Health Organization for treatment of cancer pain. Nonopioid and opioid
      analgesics are the cornerstone of pharmacological pain management. Tricyclic
      antidepressants and anticonvulsants can be very effective for the treatment of
      certain types of neuropathic pain. In addition to treating the pain per se,
      attention should be given to prevention of disease progression and exacerbation,
      as maintaining function is of prime importance. Nursing home residents with
      severe dementia challenge the practitioner's pain assessment skills; an empirical
      approach to treatment may sometimes be warranted. The success of treatment should
      be measured by improvement in pain intensity as well as physical, psychosocial
      and cognitive function. Effective pain management may impact any or all of these
      functional domains and, therefore, substantially improve the nursing home
      resident's quality of life.

PMID- 11232739
TI  - Improving the well-being of elderly patients via community pharmacy-based
      provision of pharmaceutical care: a multicentre study in seven European
      countries.
AB  - OBJECTIVE: This study aimed to measure the outcomes of a harmonised, structured
      pharmaceutical care programme provided to elderly patients (> or =65 years of
      age) by community pharmacists in a multicentre international study performed in 7
      European countries. DESIGN AND SETTING: The study was a randomised, controlled,
      longitudinal, clinical trial with repeated measures performed over an 18-month
      period. A total of 104 intervention and 86 control pharmacy sites participated in
      the research and 1290 intervention patients and 1164 control patients were
      recruited into the study. MAIN OUTCOME MEASURES AND RESULTS: A general decline in
      health-related quality of life over time was observed in the pooled data;
      however, significant improvements were achieved in patients involved in the
      pharmaceutical care programme in some countries. Intervention patients reported
      better control of their medical conditions as a result of the study and cost
      savings associated with pharmaceutical care provision were observed in most
      countries. The new structured service was well accepted by intervention patients
      and patient satisfaction with the services improved during the study. The
      pharmacists involved in providing pharmaceutical care had a positive opinion on
      the new approach, as did the majority of general practitioners surveyed. The
      positive effects appear to have been achieved via social and psychosocial aspects
      of the intervention, such as the increased support provided by community
      pharmacists, rather than via biomedical mechanisms. CONCLUSIONS: This study is
      the first large-scale, multicentre study to investigate the effects of
      pharmaceutical care provision by community pharmacists to elderly patients.
      Future research methodology and implementation will be informed by the experience
      gained from this challenging trial.

PMID- 11232740
TI  - Flexural wave propagation velocity and bone mineral density in females with and
      without tibial bone stress injuries.
AB  - STUDY DESIGN: Case-control nonexperimental design. OBJECTIVES: To compare
      flexural wave propagation velocity (FWPV) and tibial bone mineral density (BMD)
      in women with and without tibial bone stress injuries (BSIs). BACKGROUND:
      Physical therapists, particularly in military and sports medicine settings,
      routinely diagnose and manage stress fractures or bone stress injuries. Improved
      methods of preparticipation quantification of tibial strength may provide markers
      of BSI risk and thus potentially reduce morbidity. METHODS AND MEASURES: Bone
      mineral density, FWPV, bone geometry, and historical variables were collected
      from 14 subjects diagnosed with tibial BSIs and 14 age-matched controls; all 28
      were undergoing military training. RESULTS: No difference was found between
      groups in FWPV and tibial BMD when analyzed with t tests (post hoc power = 0.89
      and 0.81, respectively). Furthermore, no difference was found in tibial length,
      tibial width, femoral neck BMD, and lumbar spine BMD among the groups. There were
      no differences between the 2 groups in smoking history, birth control pill use,
      and onset of menarche. Finally, sensitivity and positive likelihood ratios for
      FWPV (0.14 and 0.63), tibial BMD (0.0 and 0.0), and lumbar BMD (0.18 and 2.0)
      were low, while specificity was high (0.77, 0.93, and 0.91, respectively).
      CONCLUSION: Current bone analysis devices and methods may not be sensitive enough
      to detect differences in tibial material and structure; local stresses on bone
      may be more important in the development of BSIs than the overall structural
      stiffness.

PMID- 11232741
TI  - Anatomical variations of the scalene triangle: dissection of 10 cadavers.
AB  - STUDY DESIGN: Cadaver dissection to study the anatomy of the scaleni muscles and
      surrounding structures. OBJECTIVES: To analyze in depth the anatomy of the
      scaleni muscles and surrounding structures, and to further document anatomical
      variations which have been reported in the literature. BACKGROUND: The literature
      reported variations in the attachments of the scaleni muscles, as well as the
      presence of a scalenus minimus muscle. The importance of these muscles in the
      respiratory and musculoskeletal systems led us to study these muscles with
      dissection. METHODS AND MEASURES: We performed anatomical dissection on 10
      cadavers. The findings from the cadavers were analyzed and reported. RESULTS: The
      attachments of the 3 primary scaleni muscles (anterior, medius, and posterior)
      were variable. The actual width of the scaleni muscles (anterior, medius, and
      posterior) at the C6 tubercle and at the first rib also varied. A scalenus
      minimus was present in one cadaver and presumably present in 2 others. The
      scalenus anterior muscle arose in 20% of the specimens from C3 to C6, in 30% of
      the specimens from C3 to C7, in 20% of the specimens from C4 to C5, and in 30% of
      the specimens from C4 to C6. The scalenus anterior muscle arose from C3 in 50% of
      the dissections. An attachment to C7 was observed in 30% of the cadavers. The
      widths of the scalenus anterior muscles at their insertion were between 8 and 17
      mm. The scalenus medius muscle arose in 40% of the specimens from C2 to C6. In
      60% of the cadavers, the scalenus medius muscle had an attachment to C7. Fifty
      percent of the scalenus medius muscles arose from C2 and 50% also had an origin
      from C1. The widths of the scalenus medius muscles at their insertion were
      between 10 and 20 mm with a mean of 15.5 mm. Fifty percent of the scalenus
      posterior muscles arose from C4 to C6 and 50% arose from C5 to C6. CONCLUSIONS:
      Variations were found in the attachments and the size of the scaleni muscles.
      These variations may effect the size of the scalene triangle, and thus, may
      potentially result in varied signs and symptoms in patients who have cervical,
      thoracic, and rib dysfunctions. Clinical implications were postulated.

PMID- 11232738
TI  - Antipsychotic medications and the elderly: effects on cognition and implications
      for use.
AB  - Despite being frequently prescribed in the elderly, antipsychotic medications are
      commonly associated with adverse effects in this population, including sedative,
      orthostatic and extrapyramidal adverse effects. Growing evidence suggests that
      antipsychotics can also cause deleterious cognitive effects in some elderly
      patients. Preclinical and growing clinical evidence indicates that inhibitory
      effects on dopaminergic, cholinergic and histaminergic neurochemical systems may
      account for antipsychotic-associated cognitive impairment in the elderly. A
      review of published reports of the cognitive effects of antipsychotics in the
      elderly suggests that newer antipsychotic medications may possess a more
      favourable cognitive profile than that of traditional agents in this population.
      The cognitive effect that a specific antipsychotic will have in the elderly,
      however, is likely better predicted by considering the pharmacodynamic action of
      an individual agent in combination with the pathophysiology of the condition
      being treated. Agents with relatively weak dopamine inhibiting effects (e.g.
      clozapine and quetiapine), for example, would theoretically have a cognitive
      profile superior to that of agents with higher degrees of dopaminergic inhibition
      (all traditional agents, risperidone, olanzapine and ziprasidone) when used for
      conditions associated with diminished dopamine function (e.g. idiopathic
      Parkinson's disease). Drugs with weak anticholinergic effects (high-potency
      traditional agents, risperidone, quetiapine and ziprasidone) would theoretically
      be less likely to cause cognitive impairment than agents with high degrees of
      cholinergic receptor blocking actions (clozapine and olanzapine) when treating
      patients with impaired cholinergic function (e.g. Alzheimer's disease).
      Cholinergic agonist effects of clozapine and olanzapine may, however, mitigate
      potential adverse cognitive effects associated with the cholinergic blocking
      actions of these agents. Large, rigorous trials comparing the cognitive effects
      of antipsychotics with diverse pharmacodynamic actions are lacking in the elderly
      and are needed.

PMID- 11232742
TI  - New method to assess scapular upward rotation in subjects with shoulder
      pathology.
AB  - STUDY DESIGN: Test-retest repeated measures and correlational design. OBJECTIVES:
      To examine the reliability and validity of a "modified" digital inclinometer to
      assess scapular upward rotation during humeral elevation in the scapular plane
      BACKGROUND: Evidence exists that scapular motion is related to shoulder
      pathology; however, evaluation and treatment planning for shoulder rehabilitation
      often fails to include an objective assessment of scapular motion. METHODS AND
      MEASURES: Two-dimensional measurements by the inclinometer were taken with the
      arm in a static position. These data were compared to 3-dimensional measurements
      obtained using a magnetic tracking device with the arm fixed and during arm
      movement. Both methods were used to assess scapular upward rotation positions
      with the arm at rest and at 60 degrees , 90 degrees , and 120 degrees of humeral
      elevation in the scapular plane. Both scapulae were tested on a total of 39
      subjects, 16 with shoulder pathology and 23 without. Reliability was assessed
      using repeated measurements from the inclinometer. Validity was assessed using 2
      separate comparisons: inclinometer and magnetic tracking device under static arm
      conditions and inclinometer and magnetic tracking device during active arm
      elevation. Reliability and validity were assessed at all 4 arm positions.
      RESULTS: Intraclass correlation coefficients (ICC [3,1]) varied from 0.89 to
      0.96. Pearson Product Moment correlation coefficients, used to assess validity of
      the static inclinometer, varied from r = 0.74 to 0.92 compared with the static
      magnetic tracking measures, and from r = 0.59 to 0.73 compared with the active
      magnetic tracking measures taken during arm elevation. CONCLUSIONS: The
      "modified" digital inclinometer demonstrated good to excellent intrarater
      reliability and good to excellent validity when measuring scapular upward
      rotation during static positions of humeral elevation in the scapular plane.

PMID- 11232743
TI  - Analysis of pain behavior profiles and functional disability in outpatient
      physical therapy clinics.
AB  - STUDY DESIGN: Descriptive, ex post facto. OBJECTIVES: To determine the proportion
      of physical therapy outpatients with pain who exhibit various pain behavior
      profiles, and to determine whether there are differences in functional disability
      across the profiles. BACKGROUND: Physical therapists treat many patients who have
      chronic pain. Research suggests that early identification and multidisciplinary
      treatment are effective and economical for these patients. The Multidimensional
      Pain Inventory (MPI) and the Pain Disability Index (PDI) are potential screening
      tools that could be used in physical therapy clinics to determine which patients
      should be referred for multidisciplinary treatment. METHODS AND MEASURES: MPI and
      PDI data were gathered on 57 physical therapy outpatients (mean age 44.3 +/- 14.5
      years, 22 men and 35 women) with pain of 3 or more months duration. ANOVA was
      used to analyze differences in mean PDI scores across the MPI profiles. RESULTS:
      Of all patients, 42.1% fit the Adaptive Coper profile, 29.8% fit the
      Interpersonally Distressed profile, and 28.1% fit the Dysfunctional profile.
      There were significant differences in PDI scores among profile groups. Post hoc
      analysis showed that the PDI scores of the Adaptive Coper and Interpersonally
      Distressed groups were different from the Dysfunctional group, but that there was
      no difference between the Adaptive Coper and Interpersonally Distressed groups.
      CONCLUSIONS: Many patients in outpatient physical therapy settings exhibit
      behavioral, affective, and cognitive characteristics associated with chronic
      pain. Thirty-three patients (57.9%) had MPI profiles (interpersonally distressed
      and dysfunctional) that suggest they might benefit from multidisciplinary
      treatment.

PMID- 11232744
TI  - Biomechanical basis for stability: an explanation to enhance clinical utility.

PMID- 11232745
TI  - Rapid tranquilization with olanzapine in acute psychosis: a case series.
AB  - Acute, high-dose loading strategies (rapid neuroleptization) with the first
      generation antipsychotics administered orally or parenterally, alone or combined
      with benzodiazepines, have been a commonly used treatment paradigm for
      controlling acutely agitated psychotic patients. The rationale was to achieve
      high plasma levels of drug within a shorter time period, resulting in rapid
      symptom mitigation. However, studies have shown that rapid neuroleptization with
      first-generation antipsychotics is associated with a greater incidence of side
      effects. To our knowledge, loading strategies with second-generation
      antipsychotics have not been investigated, primarily owing to a need for dose
      titration. Olanzapine, a second-generation antipsychotic, is well tolerated in
      doses ranging from 5 to 20 mg. The objective of this report was to determine
      experience with the use of up to 20 mg of an oral loading dose of olanzapine
      administered within 4 hours in the treatment of patients early in an acute
      psychotic phase of their illness. In the reported case series of 57 patients,
      olanzapine initiated at 15 to 20 mg/day was a safe and effective medication for
      rapidly calming the agitation of acutely agitated psychotic patients (rapid
      tranquilization). Furthermore, dose reduction over 2 to 3 weeks was achieved in a
      number of patients without appreciable loss of efficacy.

PMID- 11232746
TI  - Effective resolution with olanzapine of acute presentation of behavioral
      agitation and positive psychotic symptoms in schizophrenia.
AB  - Behavioral agitation and prominent positive psychotic symptoms often characterize
      the acute presentation of schizophrenia. The clinical treatment goal is a rapid
      control of these symptoms. The relative efficacy of olanzapine, a novel
      antipsychotic drug, was compared with that of the conventional antipsychotic drug
      haloperidol. A post hoc analysis conducted on a large multicenter, double-blind,
      6-week study of acute-phase patients with DSM-III-R schizophrenia or
      schizophreniform or schizoaffective disorders treated with olanzapine (5-20
      mg/day) or haloperidol (5-20 mg/day) assessed the treatment effects on agitation
      (Brief Psychiatric Rating Scale [BPRS] agitation score) and positive symptoms
      (BPRS positive symptom score). Overall, olanzapine-treated patients experienced
      significantly greater improvement in behavioral agitation than did haloperidol
      treated patients (last observation carried forward [LOCF]; p < .0002). Both
      groups showed similar reductions in agitation scores during the first 3 weeks of
      therapy; olanzapine was associated with significantly greater improvements at
      weeks 4, 5, and 6 (observed cases [OC]). Similarly, patients with predominantly
      positive psychotic symptoms experienced significantly greater improvement in BPRS
      positive symptom scores with olanzapine compared with haloperidol (LOCF; p =
      .013). In olanzapine-treated patients, improvement in BPRS agitation and positive
      symptom scores was significantly greater at weeks 4, 5, and 6 (agitation scores,
      p < or = .01; positive symptom scores, p < .05) (OC). These data suggest that
      olanzapine may be considered a first-line treatment for the patient in an acute
      episode of schizophrenia.

PMID- 11232747
TI  - The efficacy of a rapid-acting intramuscular formulation of olanzapine for
      positive symptoms.
AB  - Rapid tranquilization of acutely psychotic patients with schizophrenia is usually
      carried out using typical antipsychotic agents. The objective of such treatment
      is to control agitation, not to treat psychosis, which usually responds only
      after a few weeks of treatment. An intramuscular formulation of the atypical
      antipsychotic olanzapine was developed for treatment of agitation in acutely
      psychotic patients. Studies conducted to assess control of agitation in
      schizophrenia also investigated the positive symptom efficacy of olanzapine when
      used to provide rapid tranquilization. This article summarizes the results of 3
      clinical trials with intramuscular olanzapine with regard to positive symptom
      efficacy as measured by the Brief Psychiatric Rating Scale (BPRS; 0-6 scale)
      positive subscale. In 2 open-label trials, patients treated with intramuscular
      olanzapine experienced a mean decrease from baseline in BPRS positive subscale
      score. In 1 double-blind clinical trial of intramuscular olanzapine versus
      intramuscular haloperidol and intramuscular placebo, the mean decrease from
      baseline in BPRS positive subscale score for patients treated with intramuscular
      olanzapine was statistically significant (p < .05). In all 3 studies, positive
      symptom improvement continued following transition to oral olanzapine. These
      results suggest that intramuscular olanzapine has positive symptom efficacy early
      in the course of treatment and may provide a smooth transition to maintenance
      therapy with oral olanzapine.

PMID- 11232748
TI  - An efficacy analysis of olanzapine treatment data in schizophrenia patients with
      catatonic signs and symptoms.
AB  - Thirty-five patients suffering from schizophrenia, as diagnosed by the Diagnostic
      and Statistical Manual of Mental Disorders, Fourth Edition, were preselected from
      7 clinical trials according to a priori criteria of catatonic signs and symptoms
      based on 3 Positive and Negative Syndrome Scale (PANSS) items: scores for PANSS
      item 19 (mannerism and posturing) and either item 4 (excitement) or item 21
      (motor retardation) had to exceed or equal 4 at baseline. This particular patient
      population represents a severely psychotic sample: mean +/- SD PANSS total scores
      at baseline were 129.26 +/- 19.76. After I week of olanzapine treatment, mean
      PANSS total score was decreased significantly (-13.14; p < .001), as was mean
      PANSS total score after 6 weeks of olanzapine treatment (-45.16; p < .001);
      additionally, the positive subscale, negative subscale, and mood scores improved
      significantly. A significant improvement in the catatonic signs and symptoms
      composite score was also observed at week 6 (-4.96; p < .001). The mean +/- SD
      daily dose of olanzapine was 18.00 +/- 2.89 mg after 6 weeks of treatment. The
      present data analysis suggests the efficacy of olanzapine in the treatment of
      severely ill schizophrenic patients with nonspecified catatonic signs and
      symptoms.

PMID- 11232749
TI  - Evidence for the effectiveness of olanzapine among patients nonresponsive and/or
      intolerant to risperidone.
AB  - BACKGROUND: This multicenter, open-label study evaluated the efficacy and safety
      of olanzapine in patients with schizophrenia who had been nonresponsive or
      intolerant to a course of risperidone (mean duration of risperidone treatment =
      46.3 days). METHOD: A total of 34 patients with DSM-III-R and ICD-9 schizophrenia
      entered this trial. Twenty-five patients were nonresponsive to previous
      risperidone treatment, 6 patients were intolerant to the risperidone treatment,
      and 3 patients listed both reasons for discontinuation of risperidone. Patients
      were treated across a dose range of 5 to 25 mg/day of olanzapine. The primary
      efficacy variable was baseline to endpoint change in Positive and Negative
      Syndrome Scale (PANSS) score. Safety was assessed using the Clinical Global
      Impressions-Severity of Illness scale. RESULTS: Improvement from baseline PANSS
      score (mean +/- SD PANSS score = 119.4 +/- 26.9) was evident at the week-6
      midpoint (-22.2 +/- 19.5) and at the week-14 endpoint (-28.7 +/- 22.3). On
      average, severity ratings were reduced from baseline by 25% after 14 weeks of
      olanzapine therapy. Twenty olanzapine-treated patients (58.8%) achieved the a
      priori-defined response criterion of > or = 20% reduction in PANSS total score.
      Among patients who met the response criterion, 50% (10/20) had done so by the
      fourth week. These clinical improvements occurred across a broad range of symptom
      domains and included reductions in PANSS positive, negative, general
      psychopathology, and mood subscores. No statistically significant differences
      were found on any efficacy measure at any visit between the patients who were
      nonresponsive to risperidone compared with those who were intolerant to
      risperidone. Olanzapine was well tolerated, with no subject discontinuing early
      owing to an intolerable adverse event that could be conclusively linked to
      olanzapine. CONCLUSION: The results of this open-label study suggest that
      olanzapine may be an effective alternative for schizophrenic patients who are
      nonresponsive and/or intolerant to risperidone treatment. Moreover, the results
      underscore the differential pharmacology that exists among the newer
      antipsychotic agents.

PMID- 11232750
TI  - Introduction: a new era in the pharmacotherapy of psychotic disorders.

PMID- 11232751
TI  - Cardiac safety parameters of olanzapine: comparison with other atypical and
      typical antipsychotics.
AB  - Alterations of electrocardiogram results and cases of sudden cardiac death have
      been reported since the beginning of neuroleptic treatment. In particular, a
      temporal association exists between some antipsychotics and prolongation of the
      heart rate-corrected QT interval (QTc), an event that may increase the risk for
      developing a potentially fatal ventricular tachycardia arrhythmia known as
      torsades de pointes if it significantly exceeds normal intraindividual and
      interindividual variation. Although the incidence of serious adverse cardiac
      events in response to antipsychotic medications is relatively low, any
      possibility for the occurrence of cardiotoxicity warrants continued study. The
      present article reviews important differences among antipsychotic drugs in the
      potential for, and occurrence of, serious adverse cardiac outcomes and suggests
      that olanzapine, as therapeutically administered to patients with schizophrenia
      and related psychoses, does not contribute significantly to a QTc prolongation
      that could result in potentially fatal ventricular arrhythmias.

PMID- 11232752
TI  - Weight change and atypical antipsychotic treatment in patients with
      schizophrenia.
AB  - Schizophrenic patients who have been prescribed atypical antipsychotics have a
      potential risk of gaining weight. The implications of weight gain for clinical
      care may differ depending on whether a patient is underweight or overweight at
      baseline. The exact mechanism for weight gain is not known, but several factors
      have been identified that can help predict which patients are at risk for gaining
      weight. These factors include better clinical outcome, increased appetite, and
      low baseline body mass index. In patients treated with olanzapine for up to 3
      years, weight gain trended toward a plateau at approximately 36 weeks. Weight
      gain interventions, including behavioral modifications, show promise in
      controlling or reducing weight in patients treated with antipsychotics.

PMID- 11232753
TI  - Superior efficacy of olanzapine over haloperidol: analysis of patients with
      schizophrenia from a multicenter international trial.
AB  - BACKGROUND: Previously, a double-blind, 6-week, parallel-group trial compared the
      therapeutic profiles of olanzapine (5-20 mg/day; N = 1,336) and haloperidol (5-20
      mg/day; N = 660) in 1996 patients with DSM-III-R schizophrenia (83.1%) or
      schizophreniform (1.9%) or schizoaffective disorders (15.0%) and showed
      olanzapine to have a superior, broader spectrum of efficacy as well as a more
      favorable adverse event profile. The present post hoc analysis examined the
      efficacy of olanzapine compared with haloperidol in the schizophrenic cohort of
      that study and in subgroups of schizophrenic patients defined by baseline symptom
      profile and course of illness. METHOD: A total of 1,658 patients were included.
      Patients were included in analyses of change if they had both a baseline and at
      least 1 postbaseline measurement (N = 1,622; 1,096 olanzapine-treated patients,
      526 haloperidol-treated patients). An analysis of variance was used to compare
      treatment effects on efficacy measurements including the Brief Psychiatric Rating
      Scale (BPRS; scored 0-6) and the Positive and Negative Syndrome Scale (total,
      positive subscale, and negative subscale scores). RESULTS: Olanzapine-treated
      patients exhibited statistically significantly greater improvements from baseline
      (last observation carried forward) on all efficacy measurements. Olanzapine
      treated patients with predominantly positive, predominantly negative, or mixed
      symptoms had statistically significantly greater improvements in BPRS total
      scores compared with similar haloperidol-treated patients. Patients with
      primarily chronic negative symptoms and patients with chronic or subchronic
      courses of illness had statistically significantly greater mean improvements from
      baseline on the BPRS total with olanzapine compared with haloperidol.
      Furthermore, within the olanzapine treatment group, patients with a subchronic
      course of illness had greater mean improvements than patients with a chronic
      course of illness. CONCLUSION: Olanzapine was more effective than haloperidol in
      treating a varied spectrum of patients with schizophrenia, including patients
      with positive, negative, or mixed symptom profiles and either a chronic or
      subchronic course of illness.

PMID- 11232754
TI  - Effects of anti-oxidizing vitamins on in vitro cultured porcine neonatal
      pancreatic islet cells.
AB  - Oxidative stress may cause severe cellular damage to both allo- and xeno
      transplanted islets, additional to islet graft-directed immunity, in diabetic
      patients. We thus aimed to examine the effects of antioxidants on in vitro
      culture-maintained, neonatal porcine cell clusters (NPCCs). NPCCs were treated
      with antioxidants (vitamins D3 and E) by a certain time of their maturation and
      differentiation process. Insulin recovery showed that both vitamins D3 and E,
      unlike untreated controls, resulted in preservation of the islet function for
      significantly long periods of time. Such effects were also confirmed during NPCCs
      in vitro static incubation with high glucose. Furthermore, morphologic
      examination of NPCCs demonstrated that at 16 days of cell culture beta-cell
      clusters were significantly larger and more intact when exposed to the vitamins
      as compared to controls. According to these preliminary results, because the
      employed vitamins, known to retain anti-oxidizing properties, seemed to clearly
      improve NPCCs morphology and function, they may represent a potentially useful
      tool for islet culture maintenance in the pre-transplant time period.

PMID- 11232755
TI  - Alpha-lipoic acid treatment ameliorates metabolic parameters, blood pressure,
      vascular reactivity and morphology of vessels already damaged by streptozotocin
      diabetes.
AB  - The present study investigated the effects of alpha-lipoic acid treatment (50
      mg/kg/day) on the metabolism and vascular condition already damaged by
      streptozotocin (STZ)-diabetes in rats. Carbohydrate and lipid metabolism,
      oxidative stress and antioxidant status were assessed in non-diabetic controls,
      12-week untreated diabetic and 12-week treated diabetic (untreated for 6 weeks
      and then treated with alpha-lipoic acid for the last 6 weeks) rats. Blood
      pressures of rats were measured by tail-cuff method. Vascular reactivity was
      evaluated in isolated aortic rings. Morphology of aorta was examined by electron
      microscopy technique. Alpha-lipoic acid treatment effectively reversed body
      weight, blood glucose, plasma insulin, cholesterol, triglycerides and lipid
      peroxidation levels of diabetic animals. STZ-diabetes resulted in increased blood
      pressure, which was partially improved by alpha-lipoic acid treatment. Although
      the superoxide dismutase (SOD) activity in aortic homogenates was not changed by
      diabetes or antioxidant treatment, catalase or glutathione peroxidase (GPx)
      activity significantly increased in untreated diabetic rats. Alpha-lipoic acid
      treatment improved catalase activity in diabetic aorta. The contractile effect of
      phenylephrine markedly increased in diabetic rings, which was completely reversed
      by alpha-lipoic acid treatment. The maximum vasorelaxant response of pre
      contracted aortic rings exposed to cumulatively increased concentrations of
      acetylcholine was unaffected by diabetes or antioxidant treatment. Sodium
      nitroprusside-induced endothelium-independent relaxations were similar in all
      experimental groups. Various alterations caused by STZ-diabetes in aorta
      structure were partially ameliorated by alpha-lipoic acid treatment. The potency
      of alpha-lipoic acid on the reversal of hypertension by affecting vascular
      reactivity and morphology as well as general metabolism of diabetic rats confirms
      the importance of hyperglycemia-induced oxidative stress in the development of
      diabetes-induced vascular complications and suggests a potential therapeutic
      approach.

PMID- 11232756
TI  - Hyperhomocysteinemia in poorly controlled type 2 diabetes patients.
AB  - Elevated blood level of homocysteine is strongly related to an increased risk for
      atherosclerosis and cardiovascular disease. The role of homocysteine in Type 2
      diabetes vascular complications remains unclear. Our objective was to investigate
      homocysteine levels in poorly controlled Type 2 diabetic patients, who are at
      increased risk of vascular complications development. Forty-four Type 2 diabetic
      patients with no symptoms of any cardiovascular disease were divided into 2
      groups: 26 patients with poor metabolic control treated with oral agents (aged
      66.8 +/- 5.4 yr, diabetes duration 11.9 +/- 4.1 yr, fasting plasma glucose 13.9
      +/- 4.6 mmol/l, HbA1C 9.8 +/- 1.6%), 18 well-matched diabetic patients well
      controlled with oral agents (aged 65.8 +/- 4.7 yr, diabetes duration 10.9 +/- 4.2
      yr, fasting plasma glucose 7.3 +/- 2.4 mmol/l, HbA1c 6.6 +/- 0.7%). The controls
      were 12 healthy subjects. Fasting total plasma homocysteine and plasma insulin
      concentrations were measured. Plasma total homocysteine concentrations were
      significantly higher in poorly controlled than in well-controlled diabetic
      patients and controls (17.1 +/- 4.5 vs 8.2 +/- 3.9 and 6.5 +/- 4.9 micromol/l
      respectively, p < 0.001). Insulinemia showed an inverse correlation with
      homocysteine levels (8.3 +/- 5.2 vs 14.6 +/- 5.2 and 9.3 +/- 6.1 microlU/ml, p <
      0.001; r = -0.32, p < 0.05). HbA1c values correlated positively with homocysteine
      concentrations in poorly controlled subjects (r = 0.41; p < 0.05). In conclusion,
      chronic poor metabolic control of Type 2 diabetes is characterized by elevation
      of plasma homocysteine concentration, which also inversely correlates with
      endogenous insulin levels. These results may add to the understanding of the
      increased frequency and mechanisms of vascular damage in diabetes mellitus.

PMID- 11232757
TI  - Sympathetic nervous system and hypertension in diabetic patients.
AB  - Although it has been demonstrated that the sympathetic nervous system
      participates in the genesis of essential hypertension, it is still unclear
      whether this system can also account for the increased incidence of arterial
      hypertension in diabetic patients. However, there are some observations which
      make this hypothesis extremely likely. In fact, it has been demonstrated that in
      diabetic normotensive patients the reflex control of the sympathetic discharge is
      normal, but in hypertensive patients there are some derangements of the autonomic
      nervous tone control which may contribute to increasing the incidence of arterial
      hypertension in patients with Type 2 diabetes mellitus. In particular, on the one
      hand, it has been reported that in hypertensive patients hyperinsulinemia is able
      to induce a reflex activation of the sympathetic tone which is 3-fold higher than
      that observed in normotensive subjects. On the other hand, it has been
      demonstrated that this abnormal sympathetic response is particularly harmful in
      subjects prone to develop essential hypertension since they are characterized by
      vascular insulin resistance, which plays a permissive role in the development of
      essential hypertension. Vascular insulin resistance is a type of endothelial
      dysfunction which impairs the insulin modulation of the vascular effects of
      sympathetic nervous activation.

PMID- 11232758
TI  - Clinical evaluation of arterial baroreflex activity in diabetes.
AB  - The clinical and prognostic relevance of the evaluation of the arterial
      baroreflex is now firmly established in clinical cardiology, where a number of
      important studies have shown that impairment of arterial baroreflex has
      independent adverse prognostic value. The results, applied to diabetes, have
      generated a new perspective in our understanding of autonomic neuropathy.
      Available data indicate that in diabetes, with or without overt autonomic
      neuropathy, a widespread abnormality in the baroreflex function is a common
      finding. This abnormality is evident not only at the cardiac level, but also at
      the vascular level, by using new techniques able to provide more complete
      information on the direct baroreflex modulation of the resistance vessels. The
      question of whether this abnormality is already the consequence of neural damage
      or only the consequence of a functional involvement remains unsettled, although
      animal studies and the presence of widespread baroreflex abnormalities even in
      asymptomatic subjects tend to support the view that baroreceptor function can be
      altered due to functional and, later, structural damages of efferent nerves,
      involving both branches of the autonomic nervous system.

PMID- 11232759
TI  - Heart rate variability and autonomic diabetic neuropathy.
AB  - Aim of this paper is to briefly summarize available evidence about potential
      usefulness of heart rate variability (HRV) analysis for the clinical evaluation
      of autonomic diabetic neuropathy. HRV contains hidden information that can be
      extracted from tachogram sections of several hundred beats with spectral
      analysis. Subsequent normalization and the use of a paradigm including
      standardized stimuli (such as tilt) are commonly employed to assess autonomic
      cardiac regulation. In the resulting spectra, two major components of similar
      amplitude are usually observed (at low--LF--and high frequency--HF), their
      relative power is best appreciated using normalized units that provide an
      estimate of the balance between sympathetic and vagal modulatory activity. In
      states of sympathetic predominance, such as during orthostatic positions, LF
      increases and HF decreases. In diabetics, consistent alterations in spectral
      properties are a frequent early finding: initially a reduction of HRV (ie
      spectral power) is followed by progressive functional denervation, which is
      associated to severe autonomic dysfunction. The spectral methodology provides
      some useful potential advantages in respect to the more traditional approach
      employing several simple bedside tests. In conclusion, spectral analysis of HRV
      appears a convenient method to assess various degrees of diabetic autonomic
      dysfunction: it appears easy to perform, while giving results similar to
      traditional methods, with greater sensibility.

PMID- 11232760
TI  - Myocardial dysfunction and adrenergic innervation in patients with Type 1
      diabetes mellitus.
AB  - In this study we assess the mechanisms of exercise-induced left ventricular (LV)
      dysfunction in asymptomatic patients with Type 1 diabetes mellitus (T1DM) without
      coronary artery disease. Fourteen patients and 10 volunteers were enrolled. LV
      volume, LV ejection fraction (LVEF) and end-systolic wall stress were calculated
      by two-dimensional echocardiography at rest and during isometric exercise.
      Myocardial iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy was performed
      to assess adrenergic cardiac innervation. Diabetic subjects were classified into
      group A (n=7), with an abnormal LVEF response to handgrip (42 +/- 7%), and group
      B (n=7), with a normal response (72 +/- 8%). Baseline LVEF was normal in both
      group A and B patients. In group A patients, the LV circumferential wall stress
      LVEF relation showed an impairment in LVEF disproportionate to the level of LV
      after load. No significant changes in LVEF occurred during dobutamine, whereas
      post-extrasystolic potentiation (PESP) significantly increased LVEF (60 +/- 6% vs
      74 +/- 6%,p < 0.001); PESP at peak handgrip normalized the abnormal LVEF (42 +/-
      7% vs 72 +/- 5%, p < 0.001); and MIBG uptake normalized for body weight or for LV
      mass was lower than in normal subjects (1.69 +/- 0.30 vs 2.98 +/- 0.82 cpm/MBq
      per g,p = 0.01) and group B diabetic patients (vs 2.79 +/- 0.94 cpm/MBq per g,p =
      0.01). A linear correlation between LVEF at peak handgrip and myocardial MIBG
      uptake normalized for LV mass was demonstrated in the study patients. A defective
      blunted recruitment of myocardial contractility plays an important role in
      determining exercise LV dysfunction in the early phase of diabetic
      cardiomyopathy. This abnormal response to exercise is strongly related to an
      impairment of cardiac sympathetic innervation.

PMID- 11232761
TI  - Assessment of sympathetic innervation of the heart in diabetes mellitus using
      123I-MIBG.
AB  - Radio-labeled metaiodobenzylguanidine (MIBG) is considered an established
      sympathetic neuron imaging agent capable of scintigraphically visualizing the
      organs richly innervated by the sympathetic nervous system. Its clinical
      applications now include cardiac and pulmonary adrenergic imaging. The
      quantitative determination of global and/or regional abnormalities of MIBG heart
      uptake has been demonstrated to be very useful in several clinical settings
      representing one of the major determinants of adverse prognosis. The presence and
      the severity of autonomic neuropathy are known as important prognostic factors in
      patients with diabetes. MIBG scintigraphy is able to non-invasively assess and
      characterize the adrenergic abnormalities of the cardiac innervation also in
      these patients. In order to evaluate whether 123I-MIBG is able to reveal
      abnormalities of myocardial adrenergic function in different groups of diabetic
      patients, we performed 123I-MIBG scintigraphy in control subjects and in
      normotensive Type 1 diabetic patients with and without autonomic neuropathy (N+
      and N- patients), selected according to results of cardiovascular reflex tests.
      Regional abnormalities of adrenergic innervation were revealed in 10% of control
      subjects, in 70% of N- patients and in 100% of N+ patients. The finding of a
      higher than expected prevalence of MIBG regional abnormalities in patients
      without signs or symptoms of autonomic neuropathy allows to hypothesize that
      cardiac autonomic nervous damage occurs earlier than previously known in diabetic
      patients whose cardiovascular tests are still completely normal.

PMID- 11232762
TI  - The clinical utility of QT interval assessment in diabetes.
AB  - A prolonged (QT) interval is considered an indicator of an increased risk of
      malignant ventricular arrhythmias and/or sudden death. It has been proposed that
      autonomic neuropathy in diabetes is related to QT interval prolongation and
      higher mortality rates. More recently, the interlead difference in QT interval
      duration has been referred to as QT interval dispersion, which has proven to be
      predictive of ventricular arrhythmias and mortality in different groups of
      patients. QT interval duration and dispersion are significantly related, but are
      not concordant in a substantial number of cases in identifying patients at risk.
      The prevalence of QT prolongation in Type 1 and Type 2 diabetic (T1 and T2DM)
      patients is higher than 20%. Several studies in T1 and T2DM patients have
      confirmed the independent relation between prolonged QT interval duration and
      increased QT interval dispersion and chronic ischemic heart disease. It has been
      consistently shown that autonomic neuropathy is related to QT interval duration,
      while more controversies exist on the association with QT interval dispersion. In
      recent years 5 studies have been published which confirm the value of QT interval
      as a predictor of total mortality in diabetic as well as in non-diabetic
      subjects. Surprisingly, no data exist on the relation between the risk of sudden
      death and QT interval prolongation in diabetic patients. As corrected QT interval
      is significantly related to mortality, it could be used to stratify the death
      risk in diabetic patients, particularly those who are candidates for surgery or
      kidney and/or pancreas transplantation. We still do not know why QT interval is
      prolonged and how this abnormality leads to death: however, a simple, low-cost
      measurement, which is easily obtainable without the need of the patient's
      compliance, could help select patients who need second level diagnostic
      procedures and strict observation.

PMID- 11232763
TI  - Balamuthia mandrillaris infection.

PMID- 11232764
TI  - Characterisation of Hafnia alvei isolates from human clinical extra-intestinal
      specimens: haemagglutinins, serum resistance and siderophore synthesis.
AB  - Extra-intestinal Hafnia alvei isolates are rarely considered to be pathogenic. To
      investigate whether such strains are able to produce virulence factors, a total
      of 70 clinical H. alvei isolates was compared with clinical extra-intestinal
      isolates of other members of the enterobacterial tribe Klebsiellae (Kiebsiella
      pneumoniae, Enterobacter cloacae, Serratia marcescens). Whereas mannose-sensitive
      haemagglutination (MSHA) was less common in H. alvei (59%) than in K. pneumoniae
      (86%) and E. cloacae (89%) isolates, the incidences of mannose-resistant
      haemagglutination indicative of type 3 pili (MR/K-HA) and of serum resistance
      properties were not lower. All H. alvei strains secreted siderophores but, unlike
      the other enterobacterial species examined, the siderophore type was neither
      enterobactin nor aerobactin. Although the low pathogenicity of H. alvei isolates
      could not be attributed to any of the factors investigated, the mean number of
      factors expressed by each H. alvei isolate was significantly lower than that
      expressed by K. pneumoniae and E. cloacae isolates but did not differ
      significantly from that of S. marcescens. Based on these findings, the low
      pathogenicity of H. alvei appears to be due to its low frequency of expression of
      virulence factors as compared with clinically significant species such as K.
      pneumoniae and E. cloacae.

PMID- 11232765
TI  - Isolation and characterisation of putative adhesins from Helicobacter pylori with
      affinity for heparan sulphate proteoglycan.
AB  - A pool of heparan sulphate-binding proteins (HSBPs) from Helicobacter pylori
      culture supernates was obtained by sequential ammonium sulphate precipitation and
      affinity chromatography on heparin-Sepharose. The chromatographic procedure
      yielded one major fraction that contained proteins with heparan sulphate affinity
      as revealed by inhibition studies of heparan sulphate binding to H. pylori cells.
      Preparative iso-electric focusing, SDS-PAGE and blotting experiments, with
      peroxidase(POD)-labelled heparan sulphate as a probe, indicated the presence of
      two major extracellular proteins with POD-heparan sulphate affinity. One protein
      had a molecular mass of 66.2 kDa and a pI of 5.4, whilst the second protein had a
      molecular mass of 71.5 kDa and a pI of 5.0. The N-terminal amino acid sequence of
      the 71.5-kDa HSBP did not show homology to any other heparin-binding protein, nor
      to known proteins of H. pylori, whereas the 66.2-kDa HSBP showed a high homology
      to an Escherichia coli chaperon protein and equine haemoglobin. A third HSBP was
      isolated from an outer-membrane protein (OMP) fraction of H. pylori cells with a
      molecular mass of 47.2 kDa. The amino acid sequence of an internal peptide of the
      OMP-HSBP did not show homology to the extracellular HSBP of H. pylori, or to
      another microbial HSBP.

PMID- 11232766
TI  - Influence of iron restriction on Chlamydia pneumoniae and C. trachomatis.
AB  - Iron is an essential metabolite for pathogenic bacteria, and the specificity
      exhibited by bacteria for host-iron chelates may be correlated with host and
      tissue tropism. The effect of iron restriction on Chlamydia pneumoniae and C.
      trachomatis was studied by use of the iron-chelating compound deferoxamine.
      Growth of C. pneumoniae was inhibited much more than that of C. trachomatis and
      the effect of iron restriction largely depended on the cell line used for
      propagation. This might reflect differences in tissue tropism of the two
      chlamydial species. As iron levels are usually higher in men than in women, this
      might also be connected with the higher prevalence rate of C. pneumoniae
      antibodies in males, observed in all populations studied so far.

PMID- 11232767
TI  - Search for Chlamydia pneumoniae genes and their expression in atherosclerotic
      plaques of carotid arteries.
AB  - Samples of atherosclerotic tissue from 58 patients undergoing carotid surgery
      were analysed by tissue culture and PCR for Chlamydia pneumoniae; PCR was
      performed to detect Omp1, 16S rRNA and HSP-70 genes. To understand the active
      pathogenic role of C. pneumoniae, a reverse transcriptase-PCR (RT-PCR) assay was
      applied to detect the specific RNAs expressed either in the replicative form, or
      in the cryptic form found in chronic infection. The C. pneumoniae omp1 gene,
      encoding the major outer-membrane protein (MOMP), was detected in 13 of 58
      samples. Among these, the result was confirmed in 11 samples after amplification
      of a further target, the 16S rRNA, and the presence of the HSP-70 gene, encoding
      heat-shock protein 70, was revealed in only five cases. All the samples were
      negative for evidence of specific RNAs by RT-PCR. The presence of genomic DNA and
      absence of specific RNAs in atherosclerotic tissue samples suggests a lack of an
      active metabolic or persistent infective role for C. pneumoniae. Thus, traces of
      C. pneumoniae DNA in these samples could be due to a degradative pathway of the
      host defensive cellular and biochemical mechanisms.

PMID- 11232769
TI  - Inducible nitric oxide synthase inhibition delays death of rabies virus-infected
      mice.
AB  - A pathophysiological mechanism of cerebral damage and impairment of neuronal
      function during rabies virus infection was examined. Synthesis of nitric oxide
      (NO) and expression of the inducible nitric oxide synthase (iNOS) gene are
      strongly upregulated during rabies virus infection. Treatment of rabies virus
      infected mice with a selective inhibitor of iNOS, aminoguanidine (AG),
      significantly delayed their death. Prolonged survival was not due to suppression
      of an inflammatory response in the central nervous system. One effect of iNOS
      inhibition was at the level of viral replication. Treatment with AG delayed
      rabies virus replication by 2 days. Moreover, iNOS inhibition also suppressed an
      early phase of expression of an apoptotic gene, Caspase-1, which resulted in slow
      progression of infected cells into apoptotic death. iNOS inhibition had no effect
      on expression of the anti-apoptotic gene, bcl-2. In conclusion, iNOS inhibition
      delayed the death of rabies virus-infected mice by affecting viral replication
      and apoptotic death of infected cells.

PMID- 11232768
TI  - Enhanced production of vascular endothelial growth factor by human monocytic
      cells stimulated with endotoxin through transcription factor SP-1.
AB  - The effect of endotoxin on the regulation of vascular endothelial growth factor
      (VEGF) mRNA expression in human monocytic (THP-1) cells was examined. Endotoxic
      lipopolysaccharide (LPS) from Escherichia coli and synthetic E. coli-type lipid A
      (LA-15-PP) enhanced VEGF mRNA expression. LPS-induced VEGF mRNA accumulation was
      regulated, at least in part, at the transcriptional level. Enhancement of VEGF
      gene expression by LPS was shown by gel shift analysis and use of transcription
      factor inhibitors to be mediated via the activation of SP-1.

PMID- 11232770
TI  - The effect of human serum DNAases on the ability to detect antibiotic-killed
      Escherichia coli in blood by PCR.
AB  - PCR has proved superior to conventional blood culture for diagnosing bacteraemia
      in the presence of antibiotics. Nevertheless, even PCR might yield false-negative
      results if the template DNA were to be cleaved by serum DNAases after antibiotics
      had induced bacterial death. To evaluate the cleavage of bacterial template DNA
      by human serum DNAase I, serum samples inoculated with purified Escherichia coli
      DNA were incubated with increasing amounts of recombinant human DNAase (rhDNAase)
      and then examined by a PCR specific for E. coli. As a prerequisite of potential
      DNAase attack, the release of E. coli DNA after antibiotic-induced bacterial
      death was quantified by fluorescence microscopy and flow cytometry. Finally, the
      influence of rhDNAase on the PCR-based detection of antibiotic-killed E. coli in
      serum was assessed. The results indicated that purified E. coli DNA is remarkably
      stable in human serum; positive PCR results did not decrease significantly until
      the ratio of recombinant human DNAase I:E. coli rose to 106:1. As only 14.8-28.4%
      of the total E. coli DNA was released after antibiotic killing, the PCR-based
      detection of E. coli fell by only 10% when cefotaxime-killed E. coli were
      incubated with rhDNAase. It was concluded that human serum DNAases and antibiotic
      killing do not compromise the reliability of PCR examinations for bacteraemia.

PMID- 11232771
TI  - Detection of peptostreptococcus micros DNA in clinical samples by PCR.
AB  - Peptostreptococcus micros is a gram-positive anaerobic coccus which, although
      considered to be a natural commensal of the human oral cavity, is associated with
      periodontal, endodontal and peritonsillar infections. Identification of the
      organism has to date relied upon conventional culture methods and biochemical
      analyses. The purpose of this study was to develop a PCR method for rapid and
      specific identification of this organism in clinical samples. A pair of primers
      was selected, each of which was specific at the 3' end for P. micros DNA; they
      were used in the PCR assay, resulting in a 1074-bp product. The primers were
      shown to be specific for P. micros DNA as no PCR products were obtained when
      genomic DNA extracts from a wide range of other Peptostreptococcus species and
      other oral bacteria were used as templates. The PCR assay was then applied to the
      identification of P. micros DNA in subgingival plaque samples from adult
      periodontitis patients and pus samples from subjects with acute dento-alveolar
      abscesses. Confirmation of specific amplification of P. micros DNA was obtained
      by digestion of PCR products with the restriction endonuclease RsaI, which gives
      a unique restriction profile for P. micros, and DNA sequencing. Sixty-eight
      subgingival plaque samples from 18 patients were analysed, of which 19 (28%) were
      positive for P. micros DNA; the proportion of patients carrying P. micros DNA in
      at least one sampled site was 11 (61%) of 18. Twenty (71%) of 28 pus samples
      analysed by PCR contained P. micros DNA. These results confirm that P. micros may
      be involved in the aetiology of acute dentoalveolar abscesses and adult
      periodontitis. The PCR assay provides a more rapid and reliable alternative to
      conventional methods for identification of P. micros in clinical samples.

PMID- 11232772
TI  - Variation in Bordetella bronchiseptica flaA does not correlate with typing by
      macro-restriction analysis by pulsed-field gel electrophoresis.
AB  - A genotyping method based on PCR-RFLP analysis of the flagellin gene (flaA) was
      applied to 30 mainly feline isolates of Bordetella bronchiseptica. These isolates
      were separated into three PCR-RFLP groups with the restriction endonucleases
      HaeIII, MspI, MboI and RsaI. flaA nucleotide sequences representing each of the
      three groups differed from each other by 11-13%. One of the groups exhibited far
      greater flaA sequence identity with the cryptic flagellin gene sequence of B.
      pertussis (>97%) than with flaA sequences from representatives of the other B.
      bronchiseptica PCR-RFLP groups. Amongst the 30 isolates were at least 10
      representing each of the two major genotypes (A and B) identified in a previous
      study by macro-restriction analysis and pulsed-field gel electrophoresis (PFGE),
      as well as representatives of other less common genotypes. Each of the major PFGE
      genotypes contained strains representing more than one flagellin genotype.
      Indeed, there was no correlation between the two molecular typing methods. PFGE
      analysis may identify differences due to genomic re-arrangements rather than
      genuine variations in gene content. If so, relationships inferred on the basis of
      PFGE or other molecular methods for whole genome comparison should be treated
      with caution.

PMID- 11232773
TI  - Molecular epidemiology of Pseudomonas aeruginosa infections in a cystic fibrosis
      outpatient clinic.
AB  - Chronic respiratory infection by Pseudomonas aeruginosa is a significant
      determinant in the prognosis of cystic fibrosis patients. Cross-infection between
      cystic fibrosis patients and the prevalence of P. aeruginosa among them were
      investigated by microbiological surveillance and RAPD typing of the isolates. A
      total of 748 samples was cultured, including specimens from the respiratory tract
      (sputum or throat swabs) and hands of patients and medical staff, resulting in
      the collection of 86 isolates of P. aeruginosa from 65 samples. Prevalence of P.
      aeruginosa was 39.3% in respiratory samples, 0.2% on patients' hands and none in
      the medical staff's hand samples. RAPD typing characterised 51 genotypes and
      clonal persistence was observed in the majority of patients. These results
      suggest that cross-infection is not common in the outpatient clinic studied and a
      common source of acquisition is unlikely.

PMID- 11232774
TI  - Molecular characterisation of rough variants of Vibrio cholerae isolated from
      hospitalised patients with diarrhoea.
AB  - Seven rough isolates of Vibrio cholerae isolated as the sole infecting agent from
      patients with cholera-like diarrhoea were examined for the presence of the
      regulatory element toxR and certain virulence-associated genes of the CTX genetic
      element and V. cholerae pathogenicity island (VPI). Multiplex PCR analysis with
      wb-specific genes of either O1 or O139 origin showed that six of the seven
      isolates produced an O1 wb-specific amplicon and the remaining isolate produced
      an O139-specific amplicon. Analysis of lipopolysaccharide profiles of smooth
      variants of V. cholerae revealed the presence of long repeated units of 'O'
      polysaccharide side chains but all the rough variants appeared to be devoid of
      the latter and possessed only core oligosaccharide. PCR amplification with
      primers specific to the ctxA, ctxB, tcpA, tagA, int, aldA, toxT, LJ, RJ and toxR
      genes revealed that six of the seven rough isolates were positive for these
      genes. One isolate was found to be negative for tagA and RJ, indicating the
      presence of an altered VPI. Each of these isolates showed media-dependent
      expression of cholera toxin (CT) and produced more toxin than the reference V.
      cholerae O1 El Tor strain VC20 or O139 strain SG24 under comparable conditions.
      Studies on the clonality of these isolates by the analysis of rRNA genes
      indicated their relatedness to strains of V. cholerae O1 El Tor or O139, isolated
      during the same time period.

PMID- 11232775
TI  - Use of automated riboprinter and pulsed-field gel electrophoresis for
      epidemiological studies of invasive Haemophilus influenzae in Taiwan.
AB  - A total of 87 invasive isolates of Haemophilus influenzae isolated throughout
      Taiwan from 1994 to 1998 was collected; 57 were from children <14 years old. In
      all, 60.9% of isolates were resistant to ampicillin and produced beta-lactamase.
      Ribotyping revealed six different profiles in 55 isolates of type b, nine
      profiles in 10 isolates of non-type b and 12 profiles in 22 isolates of non
      typable H. influenzae. Among isolates from 35 cases of meningitis, 30 (86%) were
      in ribogroups 1, 2 and 3 with >90% genetic similarity. Compared with all the
      other ribogroups, ribogroups 1, 2 and 3, which encompassed all H. influenzae type
      b, were significantly more prevalent as a cause of meningitis in children <14
      years old. Further subtyping of the predominant ribogroup by pulsed-field gel
      electrophoresis (PFGE) identified differences of 0-6 bands among these isolates
      of ribogroup 1, which indicated distant relatedness. Automated ribotyping was
      found to be a useful method and was less time-consuming for molecular
      epidemiology studies of H. influenzae. PFGE is suggested as an addition to
      ribotyping to improve discrimination if H. influenzae type b is involved.
      Differentiating ribogroups between type b and non-type b H. influenzae by
      genotyping may help to understand the molecular characteristics of outbreaks,
      endemicity and value of vaccination. According to the results of ribotyping and
      PFGE, it seems possible that spread of invasive H. influenzae type b had occurred
      and ribotyping confirmed that there was no clonal spread of non-type b H.
      influenzae in Taiwan.

PMID- 11232776
TI  - Determination of the antibacterial efficacy of several antiseptics tested on skin
      by an 'ex-vivo' test.
AB  - There are many skin antiseptics commercially available. Although their
      antibacterial activity has often been well studied, their potential effectiveness
      on skin remains poorly documented. To date, in-vivo protocols designed for the
      testing of the antimicrobial efficacy of antiseptics cannot use, for ethical
      reasons, pathogenic bacteria or new formulations whose toxicity in human subjects
      is unknown. An 'ex-vivo' test was recently developed to overcome these problems.
      Freshly excised human skin from abdominal or breast reduction was placed in a
      diffusion cell containing a maintenance medium in the recipient compartment. A
      bacterial inoculum was then applied to the stratum corneum and, after a drying
      step, antiseptic formulations were evaluated for their antimicrobial activity.
      Several micro-organisms were investigated: - Staphylococcus aureus, methicillin
      resistant S. aureus (MRSA), Enterococcus faecalis, vancomycin-resistant Ent.
      faecium (VRE), S. epidermidis, Pseudomonas aeruginosa and Escherichia coli--with
      several biocides--para-chloro-meta-xylenol (PCMX, active compound of Dettol),
      povidone iodine, triclosan (in isopropanol) and chlorhexidine. Results from the
      ex-vivo test were compared with results obtained in suspension and glass-carrier
      tests. The bactericidal activity of the biocides depended upon the test performed
      and results were generally significantly different from one method to the other.
      All biocides tested in the suspension test achieved >4 log10 reduction in viable
      bacterial concentrations, apart from povidone iodine tested against Ent. faecalis
      and VRE. The antibacterial activity of biocides tested in the glass-carrier test
      was significantly lower than in the suspension test, with the exception of
      triclosan in isopropanol, which was as effective in both suspension and glass
      carrier test. In the ex-vivo test, triclosan in isopropanol achieved a log10
      reduction in viable bacterial concentration of 1.105-1.771 (with the exception of
      P. aeruginosa with 0.758 log10 reduction). PCMX, povidone iodine and
      chlorhexidine achieved log10 reductions in viable bacterial concentration of
      0.303-0.901. Chlorhexidine tested against P. aeruginosa produced a 1.94 log10
      reduction in concentration. These results confirm previous observations about the
      need for testing the antimicrobial activity of antiseptics on skin surface to
      determine their in-situ efficacy and encourage further the use of the ex-vivo
      protocol.

PMID- 11232777
TI  - Unusual cryptosporidium species recovered from human faeces: first description of
      Cryptosporidium felis and Cryptosporidium 'dog type' from patients in England.
AB  - DNA was extracted from faecal samples collected from 1680 patients in which
      Cryptosporidium oocysts were recognised by light microscopy. DNA from faeces from
      five of these patients failed to amplify by PCR three gene fragments--the
      Cryptosporidium oocyst wall protein (COWP) gene, the thrombospondin-related
      adhesive protein of Cryptosporidium-1 (TRAP-C1) gene and the thrombospondin
      related adhesive protein of Cryptosporidium-2 (TRAP-C2) gene--with primers
      designed from C. parvum sequences. However, DNA from these five patients did
      amplify cryptosporidial 18S rDNA gene fragments and a heat-shock protein (HSP70)
      gene fragment was also amplified from four of them. The purpose of this study was
      to characterise further the Cryptosporidium associated with infection in these
      patients. DNA sequence analysis of 18S rDNA genes showed that four of these
      patients were infected by C. felis, and the remaining one by an as yet un-named
      Cryptosporidium species designated the 'dog type' (C. dt). Infection by C. felis
      was further confirmed in all four patients by DNA sequence analysis of the HSP70
      gene. Oocysts present in all five samples reacted strongly with two anti
      cryptosporidial oocyst monoclonal antibodies, except for the C. dt, which was
      tested with only one of the antibodies. Two of the patients infected by C. felis
      had underlying illness; one 8-year-old male had an undefined severe inherited
      underlying condition, and the second patient, a 32-year-old male, was HIV
      positive. Two of the remaining three patients (two females aged 1 and 2 years,
      respectively) were apparently immunocompetent (one infected with C. felis and one
      with the C. dt). No information was obtained for the fifth patient. The patient
      infected by C. dt had a recent history of travel to Africa. This is the first
      report of infection with these two Cryptosporidium species in immunocompetent
      patients, and in any patient in the UK.

PMID- 11232778
TI  - Ultrasound in photoelectrochemistry: a new approach to the enhancement of the
      efficiency of semiconductor electrode processes.
AB  - A novel photoelectrochemical experiment which simultaneously allows the
      illumination of a TiO2 semiconductor electrode surface and the application of
      power ultrasound emission is described. The horn probe of an immersion horn
      transducer is modified by an oxide coated titanium tip and placed in a
      conventional three electrode electrochemical cell which allows light from a
      monochromated source to be focussed onto the electrode surface. Well-defined
      photocurrents are observed in aqueous media and for the photoinduced oxidation of
      water in acetonitrile and of 2.4-dichlorophenol in acetonitrile. The effect of
      ultrasound is to shift the observed photocurrent responses to more negative
      potentials and therefore to enhance the observed processes. Several possible
      interpretations associated with the complex effects induced by ultrasound are
      considered and a model based mainly on the extreme change of mass transport at
      the semiconductor/solution interface is suggested. Considerably enhanced
      performance for non-Nernstian processes, such as those observed in
      photoelectrochemical reactions at semiconductor electrodes, can be achieved in
      the presence of ultrasound.

PMID- 11232779
TI  - Sonication of aqueous solutions of chlorobenzene.
AB  - Sonication at two frequencies (20 and 900 kHz) was carried out on dilute (220
      ppm) aqueous solutions of chlorobenzene. The formation of chloride ions was
      followed using ion chromatography. The solutions became more colored with time;
      the absorbance maximum was around 270 nm. Some of the compounds remaining in the
      solution could be identified; they were chlorinated phenols, chloronaphthalene,
      mono and dichlorobiphenyls, etc. At the same acoustic power, the rate of chloride
      formation with 20 kHz ultrasound was greater when a probe with a larger tip area
      was used, but significantly less than the rate with 900 kHz. The use of
      ultrasound for conversion of chlorine in organic compounds in water to chloride
      can thus be performed more efficiently using a higher frequency and with a lower
      intensity (power per area). There is, however, a possibility that the toxicity of
      the aqueous solution is increased by such treatment.

PMID- 11232780
TI  - Experimental study of the ultrasound attenuation in chemical reactors.
AB  - Ultrasound is used in different domains, and in sonochemistry particularly, for
      different purposes and in various flow configurations: monophasic, two-phase and
      polyphasic reactors. In order to optimize and to design sonochemical reactors, it
      is important to describe the ultrasonic intensity space and time distribution. In
      addition, it is important to study the different parameters influencing the
      intensity profiles of the ultrasonic wave. In this work, a thermoelectric probe
      has been used to measure the ultrasonic intensity. This procedure has shown that
      the ultrasound propagation is influenced by the presence of cavitation bubbles,
      the flow regime and the presence of solid particles.

PMID- 11232781
TI  - Degradation of aqueous solution of potassium iodide and sodium cyanide in the
      presence of carbon tetrachloride.
AB  - The degradation of potassium iodide, carbon tetrachloride and sodium cyanide has
      been studied using an ultrasounic probe of 20 kHz frequency. In the case of
      potassium iodide and sodium cyanide, the rate of degradation was much higher in
      presence of CCl4. The location of the ultrasonic horn showed a significant effect
      in the degradation of CCl4.

PMID- 11232782
TI  - Lactose hydrolysis and beta-galactosidase activity in sonicated fermentation with
      Lactobacillus strains.
AB  - Milk fermentation with four Lactobacillus strains, including L. delbrueckii
      subsp. bulgaricus B-5b, L. helveticus LH-17, L. delbrueckii subsp. lactis SBT
      2080 and L. acidophilus SBT-2068, was carried out under sonicated conditions.
      Under continuous sonication, viable cell count decreased or grew less than in
      conventional fermentation, but it increased considerably in static incubation
      after sonication. Sonication caused beta-galactosidase release from lactic acid
      bacteria cells to the culture medium, thus resulting in higher total beta
      galactosidase activity. However, lactose hydrolysis was enhanced only when beta
      alactosidase was effectively released. With L. delbrueckii subsp. bulgaricus B-5b
      and L. helveticus LH-17. the degrees of lactose hydrolysis achieved were about
      75% which is much higher than those in conventional fermentation (below 40%).
      Results presented here showed that a high viable cell count and a high degree of
      lactose hydrolysis could be simultaneously achieved by a suitable sonication
      method.

PMID- 11232783
TI  - Enhancement of high-frequency acoustic cavitation effects by a low-frequency
      stimulation.
AB  - The cavitation effects given by a high-frequency pulsed ultrasound field are
      studied with and without the stimulation of a low-frequency field.
      Sonoluminescence intensity and subharmonic one-half intensity of the high
      frequency field are measured. The stimulation gives a sharp rise of both
      subharmonic and sonoluminescence intensities.

PMID- 11232784
TI  - The process (mechanism) of erosion of soluble brittle materials caused by
      cavitation.
AB  - This research determines which of the phenomena that appear during cavitation are
      responsible for the erosion of some brittle water soluble materials, such as
      gypsum and alum, when exposed to a high intensity ultrasound field over the
      cavitation level. The observation that gypsum suffers no erosion under the effect
      of an ultrasound field when the material is irradiated in a saturated solution of
      gypsum in water initiated the idea of performing this experiment.

PMID- 11232785
TI  - Human sperm immobilization effect of Carica papaya seed extracts: an in vitro
      study.
AB  - AIM: To examine if the seed extracts of Carica papaya, which showed
      antispermatogenic/sperm immobilization properties in animal models, could cause
      human sperm immobilization in vitro. METHODS: Chloroform extract, benzene
      chromatographic fraction of the chloroform extract, its methanol and ethyl
      acetate sub-fractions and the isolated compounds from the sub-fractions i.e., ECP
      1 & 2 and MCP 1 &2, of the seeds of Carica papaya were used at concentrations of
      0.1%, 0.5%, 1% and 2%. Sperm motility was assessed immediately after addition of
      extracts and every 5 minutes thereafter for 30 minutes. RESULTS: There were dose
      dependent spermicidal effects showing an instant fall in the sperm motility to
      less than 20% at 2% concentration. Isolated compounds ECP 1 & 2 were more
      effective inducing a motility of less than 10%. Many of the spermatozoa became
      vibratory on the spot. Total inhibition of motility was observed within 20-25 min
      at all concentrations of all products. Scanning and transmission electron
      microscopy revealed deleterious changes in the plasma membrane of the head and
      mid-piece of spermatozoa. Sperm viability test and the number of abnormal
      spermatozoa after completion of incubation suggested that the spermatozoa were
      infertile. The effects were spermicidal but not spermiostatic as revealed by the
      sperm revival test. CONCLUSION: The results reveal spermicidal activity in vitro
      of the seed extracts of Carica papaya.

PMID- 11232786
TI  - Sperm function tests after vasovasostomy.
AB  - AIM: To evaluate the sperm function after vasovasostomy. METHODS: Semen samples
      from 42 subjects after vasovasostomy (Group A: 1-6 months, Group B: 6-12 months;
      Group C: 12-18 months after vasectomy reversal) were investigated. Semen from 34
      normal fertile men was used as controls. Sperm function tests, including
      hypoosmotic swelling test (HOST), acridine orange (AO) fluorescence, acrosome
      reaction (triple-stain), cervical mucus penetration test (CMPT), etc were done.
      RESULTS: After vasectomy reversal, the percentage of HOST was significantly lower
      than that of the normal fertile men. In regard to AO, there were no significant
      differences between the three vasovasostomy groups and between these 3 groups and
      the controls. With triple-stain, the percentage of normal acrosome reaction was
      significantly lower in Group A as compared with the controls, but not in Groups B
      and C. There were no significant differences in the results of CMPT between the
      vasovasostomy groups and the controls. However, the number of "poor" type was
      significantly higher in Groups A and C than in the controls; the percentage of
      "negative" type were higher in Groups A and B than in the controls. CONCLUSION:
      After vasovasostomy a lower level of HOST remained for one year and gradually
      recovered after one year. Six months after vasectomy reversal, the percentage of
      acrosome reaction could be changed from lower level to normal range. The data of
      AO indicated that the genetic material (double-stranded DNA) in spermatozoa was
      not affected by vasovasostomy. To evaluate the result of CMPT after vasectomy
      reversal, not only the normal results but also the abnormal results ("poor" and
      "negative" types) should also be considered.

PMID- 11232787
TI  - Histologic changes in the mouse testis after bilateral vasectomy.
AB  - AIM: To study the effect of vasectomy on histological appearance of the testis.
      METHODS: Parkes strain mice were used as the animal model; they were bilaterally
      vasectomized (Vx) or sham-operated (So) and killed at intervals of 4, 6, 9, and
      12 months after the operation. Testes were excised from 5 Vx and 5 So mice at
      each interval and processed for histological examination. RESULTS: Testes of So
      mice showed normal histological features. By contrast, marked alterations were
      observed in the seminiferous tubules in testes of Vx mice, except in those killed
      4 months after the operation. The seminiferous epithelium in the tubules was only
      2-3 layers thick and showed much depletion of germ cells; in severe cases, the
      epithelium consisted of only a thin layer of Sertoli cells, spermatogonia and a
      few spermatocytes. Exfoliation of germ cells, occurrence of multinucleated giant
      cells and vacuolated appearance of the epithelium were of common features in the
      tubules. Furthermore, lumen of the rete testis in Vx mice was greatly dilated and
      showed accumulation of spermatozoa with immature germ cells; in mice vasectomized
      for 6-12 months, several macrophages ingesting spermatozoa were often observed in
      the lumen of the rete testis. Spermatic granuloma was also sometimes noticed in
      corpus or in cauda regions of the epididymis in mice vasectomized for 6-12
      months. CONCLUSION: We suggest that consequences of vasectomy should be
      thoroughly understood in order to make this method rather more popular as a
      reversible method of male contraception.

PMID- 11232789
TI  - Pregnancies established through intracytoplasmic sperm injection (ICSI) using
      spermatozoa with dysplasia of fibrous sheath.
AB  - AIM: Dysplasia of the fibrous sheath (DFS) is an anomaly found in
      asthenozoospermic patients with extremely low or absent motility. In order to
      determine the efficacy of ICSI in these patients, a retrospective analysis of
      ICSI results in DFS patients has been done. METHODS: Ten ICSI attempts were
      performed in 6 patients with diagnosis of Dysplasia of the Fibrous Sheath studied
      by transmission and scanning electron microscopy. RESULTS: In the cases studied,
      sperm concentration was (29.62 +/- 18.05) x 10(6)/mL, total motility was 1.14 +/-
      1.31%. Progressive motility was 0% except for one case with 0.1% . One hundred
      and three preovulatory oocytes were obtained and 94 metaphase II oocytes were
      injected. Sixty-nine of them showed two pronuclei (fertilization rate: 73.4%).
      Forty-nine embryos were obtained and 34 were transferred (mean: 3.4 embryos per
      transfer). Five pregnancies were diagnosed by beta-hCG plasma level
      determinations that resulted to be one preclinical abortion, one clinical
      abortion and three deliveries. Another pregnancy (ongoing) was achieved from a
      cryopreserved embryo transfer. CONCLUSION: These results showed that ICSI
      provides a suitable solution for patients suffering from irreversible sperm
      defects such as DFS. Nevertheless, it is mandatory to inform couples of possible
      transmission risks to offspring, which are unknown at present. Only when the
      etiology of this problem is disclosed, it will be possible to assess the real
      genetic risk.

PMID- 11232788
TI  - Early and late long-term effects of vasectomy on Zn, Cd, and Cu levels in
      prostatic fluid and serum.
AB  - AIM: To evaluate the early and late long-term effects of vasectomy on the serum
      and prostatic fluid trace elements. METHODS: In 37 vasectomized and 25 non
      vasectomized (control) men, the Zn, Cd and Cu levels in the serum and prostatic
      fluid were measured by means of inductively coupled plasma-atomic emission
      spectroscopy (ICP-AES). RESULTS: No significant difference was found in the
      prostatic Zn, Cd and Cu levels between the vasectomized and control group. The Zn
      level in the serum were significantly lower in the vasectomized men than in the
      controls (11.04 and 13.54 umol/L, respectively; P < 0.05), while the serum Cd and
      Cu levels were not significantly different between the two groups. CONCLUSION:
      Vasectomy may decrease the serum, but not the prostatic Zn levels. Its
      pathophysiological significance is worthy of further investigation.

PMID- 11232790
TI  - Comparative study on efficacy of three sperm-separation techniques.
AB  - AIM: To evaluate the comparative effectiveness of real-time sperm separation
      technique (Wang's tube method) and other two conventional methods in isolating
      high-quality sperm preparation, and to compare the spouse pregnancy rate in
      intrauterine insemination (IUI) with sperm preparations isolated by these
      methods. METHODS: The effectiveness of the real-time sperm separation technique,
      the conventional swim-up and the Percoll discontinuous density gradient methods
      in isolating sperm preparations from 60 infertile patients (20 with apparently
      normal semen and 40, abnormal semen contaminated with microorganisms and other
      impurities) was evaluated and compared. The microorganisms to be removed included
      bacteria, virus, Chlamydia trachomaticum, Ureaplsama urealyticum, etc. The spouse
      pregnancy rates in IUI with sperm preparations isolated by these three techniques
      from 80 oligoasthenoteratospermic patients were also compared. RESULTS: The
      quality (including the percentages of normal form, normal-chromatin and motile
      sperm, and the grade of motility) of sperm obtained by the real-time sperm
      separation technique was much higher (P < 0.01) as compared with those by the
      other two methods. The Wang's tube method was also more effective in removing
      microorganisms and other impurities. The method provided a higher IUI pregnancy
      rate than the other two sperm separation techniques (P < 0.05). CONCLUSION: The
      real-time sperm separation technique is the most effective method so far
      available in isolating high-quality sperm samples to be used in assisted
      reproduction.

PMID- 11232791
TI  - Cryodamage to plasma membrane integrity in head and tail regions of human sperm.
AB  - AIM: To investigate the effect of cryopreservation on the plasma membrane
      integrity in the head and tail regions of individual sperm, and the relationship
      between intact cryopreserved sperm and its motility and zona-free hamster oocyte
      penetration rate. METHODS: The eosin Y exclusion and the hypoosmotic swelling
      tests were combined to form a single test (HOS-EY test) to identify the
      spermatozoa with four types of membrane integrity. RESULTS: After
      cryopreservation, there was a marked decline in the percentage of spermatozoa
      with Type IV membrane integrity (head membrane intact/tail membrane intact), and
      a significant increase in those with Type I (head membrane damaged/tail membrane
      damaged) and Type III (head membrane damaged/tail membrane intact) membrane
      integrity (n = 50, P < 0.01). The value of Type II integrity had a wide range of
      variability, whereas Type II (head membrane intact/tail membrane damaged) was
      uncommon after thawing. A high correlation was observed between the percentage of
      Type IV integrity and sperm motility ( n = 50, r = 0.74, P < 0.01). However, the
      values of Type IV integrity were usually lower than those of post-thaw motility
      in most cryopreserved samples. The value of Type IV integrity did not correlate
      with the sperm penetration rate (n = 25, r = 0.22, P > 0.05). CONCLUSION: (1) The
      HOS-EY test has the advantage of showing four patterns of membrane integrity in
      individual spermatozoon; (2) Cryopreservation causes a significant membrane
      rupture in the head and tail regions of spermatozoa; Type III is the main
      transitional state of membrane cryodamage; (3) Cryodamage to head and tail
      membrane may occur independently; the presence of an intact tail membrane does
      not necessarily indicate the intactness of head membrane. (4) Intact membranes
      are closely related to post-thaw motility, but do not reflect the fertilizing
      potential.

PMID- 11232792
TI  - Comparative study on semen quality of one- and two-year-old ganders during the
      entire reproductive season.
AB  - AIM: To evaluate the characteristics of semen produced by one- and two-years old
      White Italian ganders during the entire reproductive season, in order to clarify
      whether the young ganders are responsible for a low fertility rate in young
      geese. METHODS: Males were kept individually in cages under natural light. Semen
      was collected by dorso-abdominal massage three times a week and routine
      examination was performed. RESULTS: The mean ejaculate volume (2.1 and 1.6 mL,
      respectively) and sperm concentration (323 and 281 x 10(6)/mL, respectively) in
      one-year-old ganders were higher than those of two-year-old ones. The percentages
      viable spermatozoa of one- and two-year-old ganders were similar (91.4 and 92.3%,
      respectively), but the percentage of normally formed viable spermatozoa was
      significantly higher in the older ganders than in the younger (47.8 and 42.9%,
      respectively, P < 0.05). CONCLUSION: The semina from one- or two-year-old Ganders
      were similar in regard to volume, sperm density and sperm motility, but the
      percentage of normally formed viable spermatozoa, which is critical for
      fertilization, was significantly higher in the older ganders. It appears that the
      ganders are responsible for the low fertility rate in young geese.

PMID- 11232793
TI  - Effect of smoking on semen quality of infertile men in Shandong, China.
AB  - AIM: To study the effect of smoking on the semen quality in infertile men in
      Shandong Province, China. METHODS: Adult non-drinker males attending the
      infertility clinic, including 110 non-smokers and 191 smokers, were recruited for
      the study. Sixty-one fertile, non-smoker and non-drinker males, who had one or
      more children, served as the controls. The smokers were divided into subgroups
      according to the amount and duration of smoking. Semen parameters (semen volume
      and sperm density, viability, motility, and morphology) were examined and seminal
      plasma contents of Zn , Cu and superoxide dismutase (SOD) determined. RESULTS:
      The semen volume and acidity, and the sperm density, viability and forward
      progression, as well as the seminal plasma contents of Zn, Cu and SOD were much
      lower in the medium, heavy and long-term smokers than in the non-smokers (P <
      0.01). The sperm density, viability and forward progression, and the seminal
      plasma Zn, Cu and SOD levels were negatively correlated with the amount and
      duration of cigarette smoking (P < 0.01). CONCLUSION: Medium, heavy and long-term
      smoking adversely affected the semen quality in a population of men visiting the
      infertility clinic in Shandong, China.

PMID- 11232794
TI  - Sperm quality in mice acutely treated with parathion.
AB  - AIM: To investigate the toxic effect of a single injection of the
      organophosphorous agropesticide, parathion, on spermatogenesis in immature male
      mice. METHODS: Seven-day old mice received a single injection of parathion
      intraperitoneally at a dose of 1/3 LD50. The epididymal sperm count, sperm
      morphology and chromatin thermal stability were analyzed 28 and 50 days after
      injection. RESULTS: Sperm counts were decreased and teratozoospermia and thermal
      denaturation of DNA increased after parathion injection. Sperm parameters were
      changed to a greater extent in younger animals, denoting a higher lability of
      spermatogenic process at its beginning. The damages could recover a long time
      after parathion administration. CONCLUSION: Organophosphorous agropesticides are
      testicular toxicants, eliciting reversible cytotoxic and cytogenetic alterations
      in germ cells.

PMID- 11232795
TI  - Changes in soluble interleukin-2 receptor level in serum and Na+-K+-exchanging
      ATPase activity in semen of infertile men caused by antisperm antibody.
AB  - AIM: To explore the possible mechanisms of male infertility caused by antisperm
      antibody (AsAb). METHODS: The soluble interleukin-2 receptor (sIL-2R) level in
      serum was analyzed by ELISA and Na+-K+-exchanging ATPase activity in semen by
      phosphorus (Pi) assay. RESULTS: The sIL-2R level in serum was significantly
      higher and the Na+K+-exchanging ATPase activity in semen significantly lower in
      AsAb positive infertile men when compared with the controls. CONCLUSION: The AsAb
      titer varies with the sIL-2R level in serum. A decrease in Na+-K+-exchanging
      ATPase activity in semen may play a role in male infertility caused by AsAb.

PMID- 11232796
TI  - Karyotypic analysis of intersexuality in Chinese from Taiyuan.
AB  - AIM: To analyze the kayrotypic patterns of 33 cases of intersexuality in Chinese
      from Taiyuan, China in order to further clarify its mechanism of development and
      the interrelationship between karyotype and phenotypic sex. METHODS: High
      resolution GTG-banding chromosome technique was used to analyze the karyotype
      patterns. RESULTS: In these patients, 57.58% were male pseudohermaphrodites
      (46,XY), 18.18%, female pseudohermaphrodites (46, XX), 12.12%, true
      hemaphrodites, and 12.12%, other karyotypes. Although testes can be seen in 88.8%
      of karyotypes with Y chromosome, 73.68% of the patients were of female social
      sex. In 42.82% of patients the social sex is in conformity with their karyotypes.
      There were 2 cases of male pseudohermaphrodites, where the sex chromosome was
      normal, but abnormalities were found in chromosomes 9, 13, or 14. CONCLUSION: Sex
      chromosomes determine the direction of gonadal and sex differentiation, while the
      development of the normal gonad and external genitalia should have the
      participation of many autosomal chromosomes as well.

PMID- 11232797
TI  - Unwarranted demand for body parts of endangered animal species for treatment of
      male infertility.

PMID- 11232798
TI  - Drug treatment of male fertility disorders.
AB  - Drug treatment remains an active domain in the therapy of male fertility
      disorders. Although there are only a few conditions that allow causal treatment,
      rational approaches are possible in many cases. Best results are obtained in
      cases requiring an anti-inflammatory treatment and in patients with an impaired
      sperm transport. High-dosage administration of FSH is a promising new
      development, aimed particularly at improving the disturbed sperm structures. A
      careful diagnostic work-up with elucidation of the underlying disease is
      essential to achieve a successful therapy.

PMID- 11232799
TI  - Carbohydrates mediate sperm-ovum adhesion and triggering of the acrosome
      reaction.
AB  - The fertilization process is the net result of a complex sequence of events that
      collectively result in the fusion of the opposite gametes. The male gamete
      undergoes continuous morphological and biochemical modifications during sperm
      development in the testis (spermatogenesis), maturation in the epididymis, and
      capacitation in the female reproductive tract. Only the capacitated spermatozoa
      are able to recognize and bind to the bioactive glycan residue(s) on the ovum's
      extracellular coat, the zona pellucida (ZP). Sperm-zona binding in the mouse and
      several other species is believed to take place in two stages. First, capacitated
      (acrosome-intact) spermatozoa loosely and reversibly adhere to the zona-intact
      ovum. In the second stage tight irreversible binding occurs. Both types of
      bindings are attributed to the presence of glycan-binding proteins (receptors) on
      the sperm plasma membrane and their complementary bioactive glycan units
      (ligands) on the surface of the ZP. The carbohydrate-mediated adhesion event
      initiates a signal transduction cascade resulting in the exocytosis of acrosomal
      contents. This step is believed to be prerequisite which allows the
      hyperactivated acrosome-reacted spermatozoa to penetrate the ZP and fertilize the
      ovum. This review focuses on the role of carbohydrate residues in sperm-ovum
      interaction, and triggering of the acrosome reaction. I have attempted to discuss
      extensive progress that has been made to enhance our understanding of the well
      programmed multiple molecular events necessary for successful fertilization. This
      review will identify these events, and discuss the functional significance of
      carbohydrates in these events.

PMID- 11232800
TI  - Effects of flavonoids from Semen Cuscutae on the reproductive system in male
      rats.
AB  - AIM: To evaluate the effects of the flavonoids extracted from the Semen Cuscutae
      (FSC) on the reproductive and endocrine functions in male rats. METHODS: (1) FSC
      were obtained from the semen of Cuscuta sinensis Lam through solvent extraction
      and polyamide columnar chromatography; (2) Effect of FSC on the reproductive
      organs was assessed in immature rats. Rats were administered FSC through gastric
      gavage at a dose of 300 mg/kg per day for 7 days and the weights of testis,
      epididymis, seminal vesicle and pituitary gland were then observed; (3) To
      observe the effect of FSC on the reproductive endocrine function: same dose level
      of FSC was given to male rats of different age groups for 7 days; on day 8, the
      plasma testosterone (T), estradiol (E2) and LH were determined by RIA, the
      specific binding of LH was estimated and the testes were weighed. (4) Effect of
      FSC on LH secretion was assessed in vitro on cultured adenohypophysis. (5) Effect
      of FSC on T secretion was assessed in vitro on Leydig cell culture. RESULTS: FSC
      increased the weights of testis, epididymis and pituitary gland, and stimulated T
      and LH secretion both in vitro and in immature rats. CONCLUSION: FSC invigorates
      the reproductive system and reproductive endocrine function in male rats.

PMID- 11232801
TI  - Coordination chemistry of the novel 5,10,15-tris(pentafluorophenyl)corrole:
      synthesis, spectroscopy, and structural characterization of its cobalt(III),
      rhodium(III), and iron(IV) complexes.

PMID- 11232802
TI  - (NH4)15[H3Mo57V6(NO)6O189(H2O)12(VO)6].approximately60H2O: new nanocompound
      obtained by chemical embellishment of [M57V6].

PMID- 11232803
TI  - Multiple ligand-based emissions from a platinum(II) terpyridine complex attached
      to pyrene.

PMID- 11232804
TI  - Three-dimensional framework constructed using nanometer-sized metallamacrocycle
      as a secondary building unit.

PMID- 11232805
TI  - To what extent can cyclometalation promote associative or dissociative ligand
      substitution at platinum(II) complexes? A combined kinetic and theoretical
      approach.
AB  - The ligand exchange rate constants for the reactions [Pt(bph)(SR2)2] + 2*SR2 -->
      [Pt(bph)(*SR2)2] + 2SR2 (bph = 2,2'-biphenyl dianion; R = Me and Et) and cis
      [PtPh2(SMe2)2] + 2*SMe2 --> cis-[PtPh2(*SMe2)2] + 2SMe2 have been determined in
      CDCl3 as a function of ligand concentration and temperature, by 1H NMR isotopic
      labeling and magnetization transfer experiments. The rates of exchange show no
      dependence on ligand concentration and the kinetics are characterized by largely
      positive entropies of activation. The kinetics of displacement of the thioethers
      from [Pt(bph)(SR2)2] with the dinitrogen ligands 2,2'-bipyridine and 1,10
      phenanthroline (N-N) to yield [Pt(bph)(N-N)], carried out in the presence of
      sufficient excess of thioether and N-N to ensure pseudo-first-order conditions,
      follow a nonlinear rate law k(obsd) = a[N-N]/(b[SR2] + [N-N]). The general
      pattern of behavior indicates that the rate-determining step for substitution is
      the dissociation of a thioether ligand and the formation of a three-coordinated
      [Pt(bph)(SR2)] intermediate. The value of the parameter a, which measures the
      rate of ligand dissociation, is constant and independent of the nature of N-N,
      and it is in reasonable agreement with the value of the rate of ligand exchange
      at the same temperature. Theoretical ab initio calculations were performed for
      both [Pt(bph)(SMe2)2] and cis-[PtPh2(SMe2)2], and for their three-coordinated
      derivatives upon the loss of one SMe2 ligand. The latter optimize in a T-shaped
      structure. Calculations were performed in the HF approximation (LANL2DZ basis
      set) and refined by introducing the correlation terms (Becke3LYP model). The
      activation enthalpies from the optimized vacuum-phase geometries are 52.3 and
      72.2 kJ moll compared to the experimental values in CDCl3 solution, 80 +/- 1 and
      93 +/- 1 kJ mol(-1) for [Pt(bph)(SMe2)2] and cis-[PtPh2(SMe2)2], respectively.
      The electrostatic potential maps of both parent compounds show a remarkable
      concentration of negative charge over the platinum atom which exerts a repulsion
      force on an axially incoming nucleophile. On the other hand, the strength of the
      organic carbanions trans to the leaving group and the stabilization of the T
      shaped intermediate in the singlet ground state may also rationalize the
      preference for the dissociative mechanism. All of the kinetic and theoretical
      data support the latter hypothesis and indicate, in particular, that dissociation
      from the complex containing the planar 2,2'-biphenyl dianion is easier than from
      its analogue with single aryl ligands. Electron back-donation from filled d
      orbitals of the metal to empty pi* of the in-plane cyclometalated rings is weak
      or absent and is not operative in promoting an associative mode of activation.

PMID- 11232806
TI  - Protonation studies of reduced ruthenium(II) complexes with polypyridyl ligands.
AB  - The pKa values associated with protonation of the one-electron reduced forms of
      series of [L'2Ru(II)L]2+ complexes [L' = bidentate polypyridyl ligand; L =
      bidentate polypyridyl ligand with additional uncoordinated N atoms in the
      aromatic ring system: e.g., dpp = 2,3-bis(2-pyridyl)pyrazine, bpz = 2,2'
      bipyrazine] were assessed using pulse radiolysis techniques by the measurement of
      spectral variations as a function of pH. A linear correlation was observed
      between pKa and E (RuL'2L2+/+) for complexes in which the protonatable ligand was
      at the same time the site of reduction. In complexes where one or more of the
      nonprotonatable ligands (L') had very low pi* energy levels [e.g. (CF3)4bpy],
      reduction occurs on a nonprotonatable ligand and a dramatic decrease in the pKa
      values was observed for the reduced species. In complexes where the energies of
      the protonatable and nonprotonatable ligands were comparable, the protonation
      behavior was consistent with some orbital mixing/ delocalization of the
      electronic charge.

PMID- 11232807
TI  - EPR studies of chromium(V) intermediates generated via reduction of chromium(VI)
      by DOPA and related catecholamines: potential role for oxidized amino acids in
      chromium-induced cancers.
AB  - The reductions of K2Cr2O7 by catecholamines, DOPA, DOPA-beta,beta-d2, N-acetyl
      DOPA, alpha-methyl-DOPA, dopamine, adrenaline, noradrenaline, catechol, 1,2
      dihydroxybenzoic acid (DHBA), and 4-tert-butylcatechol (TBC), produce a number of
      Cr(V) electron paramagnetic resonance (EPR) signals. These species are of
      interest in relation to the potential role of oxidized proteins and amino acids
      in Cr-induced cancers. With excess organic ligand, all of the substrates yield Cr
      species with signals at g(iso) approximately 1.972 (Aiso(53Cr) > 23.9 x 10(-4)
      cm(-1)). These are similar to signals reported previously but have been
      reassigned as octahedral Cr(V) species with mixed catechol-derived ligands,
      [CrV(semiquinone)2(catecholate)]+. Experiments with excess K2Cr2O7 show complex
      behavior with the catecholamines and TBC. Several weak Cr(V) signals are detected
      after mixing, and the spectra evolve over time to yield relatively stable
      substrate-dependent signals at g(iso) approximately 1.980. These signals have
      been attributed to [Cr(O)L2](L = diolato) species, in which the Cr is coordinated
      to two cyclized catecholamine ligands and an oxo ligand. Isotopic labeling
      studies with DOPA (ring or side chain deuteration or enrichment with 15N), and
      simulation of the signals, show that the superhyperfine couplings originate from
      the side chain protons, confirming that the catecholamine ligands are cyclized.
      At pH 3.5, a major short-lived EPR signal is observed for many of the substrates
      at g(iso) approximately 1.969, but the species responsible for this signal was
      not identified. Several other minor Cr signals are detected, which are attributed
      (by comparison with isoelectronic V(IV) species) to Cr(V) complexes coordinated
      by a single catecholamine ligand (and auxiliary ligands e.g. H2O), or to
      [Cr(O)L2]- (L = diolato) species with a sixth ligand (e.g. H2O). Addition of
      catalase or deoxygenation of the solutions did not affect the main EPR signals.
      When the substrates were in excess (pH > 4.5), primary and secondary (cyclized)
      semiquinones were also detected. Semiquinone stabilization by Zn(II) complexation
      yielded stronger EPR signals (g(iso) approximately 2.004).

PMID- 11232808
TI  - Optical properties of Se2- and Se2 color centers in the red selenium ultramarine
      with the sodalite structure.
AB  - The unique optical properties of Se2- radicals located in the cages of the
      sodalite structure are reported. By means of luminescence, photoluminescence
      excitation, and absorption spectroscopy, three different centers are identified.
      Two of them are Se2- anions in sites with presumably a tetrahedral Na4(4+)
      coordination and a Na3(3+) environment with cation deficiency, respectively,
      giving rise to a red luminescence band with two different progressions. The third
      center is the intermediate Se2 molecule, created photochemically by UV laser
      excitation. It induces an additional blue luminescence. The electronic properties
      of the Se2- centers, particularly in the excited states, are significantly
      influenced by steric constraints imposed by the limited space in the sodalite
      host polyhedra. Thus, the sodalite structure can be viewed as a model system for
      studying effects of this kind on chromophores imbedded in the cages of the
      zeolite-type lattice.

PMID- 11232809
TI  - Ligand substitution reactions of W6S8L6 with tricyclohexylphosphine (L = 4-tert
      butylpyridine or n-butylamine): 31P NMR and structural studies of W6S8(PCy3)n(4
      tert-butylpyridine)6-n (0 < n < or = 6) complexes.
AB  - The substitution reactions by bulky tricyclohexylphosphine (PCy3) ligands on
      W6S8L6 (L = 4-tert-butylpyridine or n-butylamine) clusters were investigated to
      prepare clusters with mixed axial ligands for low-dimensional cluster linking.
      When 4-6 equiv of PCy3 are used to react with W6S8(4-tert-butylpyridine)6 (4) in
      THF, cis-W6S8(PCy3)4(4-tert-butylpyridine)2 (1) is preferentially formed. But
      when starting with W6S8(n-butylamine)6 (2), only W6S8(PCy3)6 (3) is produced with
      6 equiv of PCy3. Other conditions with fewer equivalents of PCy3 led to mixtures
      of partially substituted complexes in the W6S8L6-n(PCy3)n (0 < or = n < or = 6, L
      = 4-tert-butylpyridine or n-butylamine) series. A significantly distorted
      structure for 1 helps to explain its preferential formation. 1H NMR spectra were
      collected for clusters 1 and 2 and 31P NMR spectra for 1 and W6S8(4-tert
      butylpyridine)6-n(PCy3)n complexes. P-P coupling through P-W-W-P is reported for
      the first time in octahedral metal clusters and shown to be very useful in
      identifying nearly all the W6S8L6-n(PR3)n complexes and their stereoisomers in
      the mixtures even before individual species are isolated.

PMID- 11232810
TI  - Preparation and characterization of [[M(dmb)2]TCNQ.xTCNQo]n polymers (M=Cu,Ag;
      dmb = 1,8-diisocyano-p-menthane; x = 0, 0.5, 1.0, 1.5; TCNQ = 7,7,8,8-tetracyano
      p-quinodimethane) and design of new semi- and photoconducting organometallic
      materials.
AB  - New thermoplastic organometallic materials of the type [[M(dmb)2]TCNQ.xTCNQo.y
      solvent], (M = Cu(I), Ag(I); dmb = 1,8-diisocyano-p-menthane; TCNQ = 7,7,8,8
      tetracyano-p-quinodimethane, x = 0, 0.5, 1.0, 1.5; solvent = none, THF or
      toluene) have been prepared and characterized from X-ray powder diffraction
      patterns, X-ray crystallography (for some Ag polymers), DSC, and conductivity
      measurements. While the [[M(dmb)2]TCNQ.xTCNQo]n polymers (M = Cu,Ag; x = 0, 0.5)
      are insulating, the others (x = 1.0 and 1.5) are semiconducting, and the relative
      conductivity is found to be a function of the molecular weight and crystallinity.
      The [[Cu(dmb)2]TCNQ.1.5TCNQ]n material is also photoconducting, while the Ag
      analogue is not. Photochemical and luminescence quenching experiments in the
      solid-state established that the Cu+ center and TCNQo act as electron donor and
      acceptor, respectively, in this photoprocess. Finally photocells of the type
      glass/SnO2/[Cu(dmb)2]TCNQ.TCNQo]n + 0.5 acceptor/Al (acceptor = TCNQo, C60 and
      TCNN (13,13,14,14-tetracyano-5,12-naphthacenequinodimethane)) have been designed
      and characterized. The quantum yields (number of photoproduced electrons/number
      of photons) are as follows: TCNQ, 1.6 x 10(-4), C60, 5 x 10(-5), TCNN, 3.0 x 10(
      4) at lambdaexc = 330 nm. X-ray data for [[Ag(dmb)2]TCNQ.2THF]n: space group
      P2(1/c), monoclinic, a = 13.5501(10), b = 9.9045(10), c = 32.564(2) A, beta =
      91.130(10) degrees, Z = 4. X-ray data for [[Ag(dmb)2]TCNQ.0.5TCNQo.0.5 toluene]n:
      space group P2(1/c), monoclinic, a = 14.3669(19), b = 9.1659(3), c = 34.012(3) A,
      beta = 92.140(8) degrees, Z = 4. X-ray data for [[Ag(dmb)2]TCNQ.1.5TCNQo]n: space
      group C2/c, monoclinic, a = 25.830(11), b = 9.680(2), c = 42.183(19) A, beta =
      104.87(4) degrees, Z = 8. X-ray data for [[Ag(dmb)2]DCTC]n: space group P2(1/a),
      monoclinic, a = 26.273(3), b = 9.730(3), c = 31.526(3) A, beta =
      112.12(2)degrees, Z = 4.

PMID- 11232811
TI  - A rational design for imidazolate-bridged linear trinuclear compounds from
      mononuclear copper(II) complexes with 2-[((imidazol-2
      ylmethylidene)amino)ethyl]pyridine (HL): syntheses, structures, and magnetic
      properties of [Cu(L)(hfac)M(hfac)2Cu(hfac)(L)] (M = ZnII, CuII, MnII).
AB  - Two mononuclear copper(II) complexes with the unsymmetrical tridentate ligand 2
      [((imidazol-2-ylmethylidene)amino)ethyl]pyridine (HL), [Cu(HL)(H2O)](ClO4)2.2H2O
      (1) and [Cu(HL)Cl2] (2), have been prepared and characterized. The X-ray analysis
      of 2 revealed that the copper(II) ion assumes a pentacoordinated square pyramidal
      geometry with an N3Cl2 donor set. When 1 and 2 are treated with an equimolecular
      amount of potassium hydroxide, the deprotonation of the imidazole moiety promotes
      a self-assembled process, by coordination of the imidazolate nitrogen atom to a
      Cu(II) center of an adjacent unit, leading to the polynuclear complexes
      [[Cu(L)(H2O)](ClO4)]n (3) and [[Cu(L)Cl].2H2O]n (4). Variable-temperature
      magnetic data are well reproduced for one-dimensional infinite regular chain
      systems with J = -60.3 cm(-1) and g = 2.02 for 3 and J = -69.5 cm(-1) and g =
      2.06, for 4. When 1 is used as a "ligand complex" for [M(hfac)2] (M = Cu(II),
      Ni(II), Mn(II), Zn(II)) in a basic medium, only the imidazolate-bridged
      trinuclear complexes [Cu(L)(hfac)M(hfac)2Cu(hfac)(L)] (M = Zn(II), Cu(II)) (5, 6)
      can be isolated. Nevertheless, the analogous complex containing Mn(II) as the
      central metal (7) can be prepared from the precursor [Cu(HL)Cl2] (2). All the
      trinuclear complexes are isostructural. The structures of 5 and 6 have been
      solved by X-ray crystallographic methods and consist of well-isolated molecules
      with Ci symmetry, the center of symmetry being located at the central metal.
      Thus, the copper(II) fragments are in trans positions, leading to a linear
      conformation. The magnetic susceptibility data (2-300 K), which reveal the
      occurrence of antiferromagnetic interactions between copper(II) ions and the
      central metal, were quantitatively analyzed for symmetrical three-spin systems to
      give the coupling parameters JCuCu = -37.2 and JCuMn = -3.7 cm(-1) with D = +/
      0.4 cm(-1) for 6 and 7, respectively. These magnetic behaviors are compared with
      those for analogous systems and discussed on the basis of a localized-orbital
      model of exchange interactions.

PMID- 11232812
TI  - New synthetic routes to biscarbonylbipyridinerhenium(I) complexes cis,trans
      [Re(X2bpy)(CO)2(PR3)(Y)n+ (X2bpy = 4,4'-X2-2,2'-bipyridine) via photochemical
      ligand substitution reactions, and their photophysical and electrochemical
      properties.
AB  - Photochemical ligand substitution of fac-[Re(X2bpy)(CO)3(PR3)]+ (X2bpy = 4,4'-X2
      2,2'-bipyridine; X = Me, H, CF3; R = OEt, Ph) with acetonitrile quantitatively
      gave a new class of biscarbonyl complexes, cis,trans[Re(X2bpy)(CO)2(PR3)(MeCN)]+,
      coordinated with four different kinds of ligands. Similarly, other
      biscarbonylrhenium complexes, cis,trans-[Re(X2bpy)(CO)2(PR3)(Y)]n+ (n = 0, Y = Cl
      ; n = 1, Y = pyridine, PR'3), were synthesized in good yields via photochemical
      ligand substitution reactions. The structure of cis,trans
      [Re(Me2bpy)(CO)2[P(OEt)3](PPh3)](PF6) was determined by X-ray analysis. Crystal
      data: C38H42N2O5F6P3Re, monoclinic, P2(1/a), a = 11.592(1) A, b = 30.953(4) A, c
      = 11.799(2) A, V = 4221.6(1) A3, Z = 4, 7813 reflections, R = 0.066. The
      biscarbonyl complexes with two phosphorus ligands were strongly emissive from
      their 3MLCT state with lifetimes of 20-640 ns in fluid solutions at room
      temperature. Only weak or no emission was observed in the cases Y = Cl-, MeCN,
      and pyridine. Electrochemical reduction of the biscarbonyl complexes with Y = Cl-
      and pyridine in MeCN resulted in efficient ligand substitution to give the
      solvento complexes cis,trans-[Re(X2bpy)(CO)2(PR3)(MeCN)]+.

PMID- 11232813
TI  - The trifluorophosphonium ion, PF3H+, preparation and structure.
AB  - The PF3H+ ion is prepared as PF3H+.SbF6-.HF by protonation of PF3 with HF/SbF5 at
      low temperatures in anhydrous HF. Crystals are obtained directly from this
      solvent. A crystal structure determination shows the presence of a pseudo
      tetrahedral PF3H+ ion with a mean P-F distance of 148.7(2) pm, a P-H distance of
      122(4) pm, and a mean PF2 angle of 106.1(1) degrees. Raman spectra were recorded
      of PF3H+SbF6-.HF and PF3D+.SbF6-.DF and assigned with the help of ab initio
      calculations. AsF3 does not react with HF/SbF5, whereas SF4 forms SF3+SbF6-.HF,
      which is isostructural with PF3H+SbF6-.HF.

PMID- 11232814
TI  - Gas-phase molecular structures of third row transition-metal hexafluorides WF6,
      ReF6, OsF6, IrF6, and PtF6. An electron-diffraction and ab initio study.
AB  - The molecular structures of WF6, ReF6, OsF6, IrF6, and PtF6 have been measured by
      electron diffraction from the gases, the last from both PtF6 itself and from a
      vapor assumed to consist of a mixture of O2 and PtF6 obtained by heating the salt
      O2PtF6. For models of Oh symmetry the bond lengths in the first three members of
      the series are essentially identical, but the Ir-F and Pt-F bonds are
      respectively about 0.01 and 0.02 A longer. Models of D4h symmetry were also
      tested for ReF6, OsF6, and IrF6 in which operation of the Jahn-Teller effect is
      thought possible. For these models the same trend was seen in the average bond
      length values. The effect of three-atom multiple scattering was also
      investigated, and experimental estimates of the effects of vibrational averaging
      ("shrinkage") on the distances were obtained. Normal-coordinate analyses based on
      the observed wavenumbers yielded stretching force constants consistent with the
      usual inverse bond-length/force-constant relationship. Ab initio molecular
      orbital optimizations of the molecules constrained to Oh symmetry were carried
      out at several levels of theory and basis-set size. Less extensive optimizations
      of ReF6, OsF6, and IrF6 with D4h symmetry were also carried out. The best overall
      agreement with both the experimental values and the distance trend for Oh
      symmetry was obtained with the Hay-Wadt (n+1)VDZ basis on the metals and the aug
      cc-pVTZ on the fluorines at the MP2 level, but these bases with B3P86 and B3PW91
      density functional theory were nearly as good and with B3LYP only slightly worse.
      The D4h structures for ReF6, OsF6, and IrF6 with the cited bases at the B3P86
      level were slightly more stable (respectively 0.8, 2.6, and 1.4 kcal/mol) with
      the axial bonds shorter by about 0.04 A in ReF6 and 0.07 A in OsF6, but about
      0.05 A longer in IrF6. The significance of these values is uncertain. The
      experimental bond lengths (rg/A) with estimated 2sigma uncertainties for the
      models of Oh symmetry are W-F = 1.829(2), Re-F = 1.829(2), Os-F = 1.828(2), Ir-F
      = 1.839(2), and Pt-F = 1.852(2); the Pt-F value from the O2PtF6 sample was
      1.851(2) A. Although the experimental data neither confirm nor refute the
      existence of the Jahn-Teller effect in ReF6, OsF6, and IrF6, they ensure that if
      present the distortion from Oh symmetry must be small.

PMID- 11232815
TI  - M-F interatomic distances and effective volumes of second and third transition
      series MF6- and MF6(2-) anions.
AB  - Synchrotron X-ray powder diffraction data (SPDD) for representative LiMF6 and
      Li2MF6 salts of the second and third transition series have provided unit-cell
      parameters and, from Rietveld analysis, M-F interatomic distances. M-F distances
      have also been obtained from X-ray single-crystal structural analyses of LiOsF6,
      Li2PtF6, and KRhF6. The LiMF6 all have the LiSbF6 structure type (space group
      R3). For M = Ta to Au the primitive unit cell volume decreases with increasing
      nuclear charge (Z), the volumes (sigma = 0.01 A3) being as follows: Ta, 111.26;
      Os, 102.42; Ir, 100.77; Pt, 99.62; and Au, 99.12 A3. A similar contraction, with
      increase in Z, occurs from Nb to Rh, the primitive cell volume (sigma = 0.01 A3)
      being: Nb, 110.92; Ru, 100.51; and Rh, 98.64 A3. For the TaF6- to AuF6- the M-F
      distances are not significantly different across the series, at approximately
      1.87(1) A; also, Nb-F, Ru-F, and Rh-F = 1.86(1) A. In each series, the a and c
      values of the hexagonal-cell representation for the LiMF6 structure (separate
      layers of MF6- and Li+ stacked along c) change smoothly. As Z increases, a
      decreases and c increases. The variation in a, like the volume change, indicates
      that the size of MF6- is decreasing with Z. The variation in c suggests that the
      charge on the F-ligand is decreasing with Z. In the trirutile Li2MF6 series, M =
      Mo to Pd, the formula-unit volume decreases with Z(Mo, 100.92(6); Ru, 98.21(1);
      Rh, 97.43(1); Pd, 96.83(1) A3) and a shortening in M-F occurs (Mo-F = 1.936(4);
      Ru-F = 1.921(7); Rh-F = 1.910(7); Pd-F = 1.899(4) A). The less abundant data for
      MF6(2-) salts of the third transition series indicate similar trends. For both
      series, M-F distances of MF6(2-) are longer by 0.03-0.09 A than in MF6-.

PMID- 11232816
TI  - Gold complexes with potentially tri- and tetradentate phosphinothiolate ligands.
AB  - Reactions of [Au(PPh3)Cl], (Bu4N)[AuCl4] and the organometallic gold complex
      [Au(damp-C1,N)Cl2] (damp- = 2-(N,N-dimethylaminomethyl)phenyl) with the
      potentially tri- and tetradentate proligands PhP(C6H3-SH-2-R-3)2 (H2L1a, R =
      SiMe3; H2L1b, R = H) and P(C6H4-SH-2)3 (H3L2) result in the formation of mono- or
      dinuclear gold complexes depending on the precursor used. Monomeric complexes of
      the type [AuL1Cl] are formed upon the reaction with [Au(damp-C1,N)Cl2], but small
      amounts of dinuclear [AuL1]2 complexes with gold in two different oxidation
      states, +1 and +3, have been isolated as side-products. The dinuclear compounds
      are obtained in better yields from [AuCl4]-. A dinuclear complex having two
      Au(III) centers can be isolated from the reaction of [Au(PPh3)Cl] with H3L2,
      whereas from the reaction with H2L1b the mononuclear [Au(Ph3P)HL1b] is obtained,
      which contains a three-coordinate gold atom. Comparatively short gold-gold
      distances have been found in the dinuclear complexes (2.978(2) and 3.434(1) A).
      They are indicative of weak gold-gold interactions, which is unusual for
      gold(III).

PMID- 11232817
TI  - Crystal and molecular structures of trifluoroacrylonitrile, F2C=CF-CN, and
      trifluorovinyl isocyanide, F2C=CF-NC, by low-temperature X-ray crystallography
      and ab initio calculations.
AB  - The structures of trifluoroacrylonitrile, F2C=CF-CN, monoclinic, P2(1/n) (no.
      14), a = 8.595(4), b = 8.748(1), c = 5.421(1) A, beta = 102.83(2) degrees, Z = 4,
      and its thermally unstable isomer trifluorovinyl isocyanide, F2C=CF-NC,
      monoclinic, P2(1/n), a = 8.501(2), b = 8.828(2), c = 5.599(2) A, beta = 101.11(2)
      degrees, Z = 4 were determined by X-ray crystal structure analysis at 113 and 128
      K, respectively, from single crystals grown by partial melting and gradient
      cooling in small glass capillaries. Selected experimental bond lengths of F2C=CF
      CN/F2C=CF-NC are as follows: C=C 1.326(1)/1.304(2), C...N 1.158(1)/1.167(2) A.
      The C-F bond lengths of the CF2 group are significantly shorter than those of the
      CF(NC) and CF(CN) units, respectively. The vibrational frequencies and molecular
      geometries of this cyanide/isocyanide pair were also calculated by ab initio
      methods for comparison with the experimental results, which were found to be in
      general agreement.

PMID- 11232818
TI  - Tetrachloro- and tetrabromoarsonium(V) cations: raman and 75As, 19F NMR
      spectroscopic characterization and X-ray crystal structures of
      [AsCl4][As(OTeF5)6] and [AsBr4][AsF(OTeF5)5] .
AB  - The salts [AsX4][As(OTeF5)6] and [AsBr4][AsF(OTeF5)5] (X = Cl, Br) have been
      prepared by oxidation of AsX3 with XOTeF5 in the presence of the OTeF5 acceptors
      As(OTeF5)5 and AsF(OTeF5)4. The mixed salts [AsCl4][Sb(OTeF5)6-nCl(n-2)] and
      [AsCl4][Sb(OTeF5)6-nCl(n)] (n > or = 2) have also been prepared. The AsBr4+
      cation has been fully structurally characterized for the first time in SO2ClF
      solution by 75As NMR spectroscopy and in the solid state by a single-crystal X
      ray diffraction study of [AsBr4][AsF(OTeFs)5]: P1, a = 9.778(4) A, b = 17.731(7)
      A, c = 18.870(8) A, alpha = 103.53(4)degrees, beta = 103.53(4) degrees, gamma =
      105.10(4) degrees, V = 2915(2) A3, Z = 4, and R1 = 0.0368 at -183 degrees C. The
      crystal structure determination and solution 75As NMR study of the related
      [AsCl4][As(OTeF5)6] salt have also been carried out: [AsCl4][As(OTeF5)6], R3, a =
      9.8741(14) A, c = 55.301(11) A, V= 4669(1) A3, Z = 6, and R1 = 0.0438 at -123
      degrees C; and R3, a = 19.688(3) A, c = 55.264(11) A, V= 18552(5) A3, Z = 24, and
      R1 = 0.1341 at -183 degrees C. The crystal structure of the As(OTeF5)6- salt
      reveals weaker interactions between the anion and cation than in the previously
      known AsF6- salt. The AsF(OTeF5)5- anion is reported for the first time and is
      also weakly coordinating with respect to the AsBr4+ cation. Both cations are
      undistorted tetrahedra with bond lengths of 2.041(5)-2.056(3) A for AsCl4+ and
      2.225(2)-2.236(2) A for AsBr4+. The Raman spectra are consistent with undistorted
      AsX4+ tetrahedra and have been assigned under Td point symmetry. The 35Cl/37Cl
      isotope shifts have been observed and assigned for AsCl4+, and the geometrical
      parameters and vibrational frequencies of all known and presently unknown PnX4+
      (Pn = P, As, Sb, Bi; X = F, Cl, Br, I) cations have been calculated using density
      functional theory methods.

PMID- 11232819
TI  - Mechanistic control of product selectivity. Reactions between cis-/trans cis
      /trans-[OsVI(tpy)(Cl)2(N)]+ and triphenylphosphine sulfide.
AB  - Reactions between the Os(VI)-nitrido complexes cis- and trans
      [Os(VI)(tpy)(Cl)2(N)]+ (tpy is 2,2':6',2"-terpyridine) and triphenylphosphine
      sulfide, SPPh3, give the corresponding Os(IV)-phosphoraniminato,
      [Os(IV)(tpy)(Cl)2(NPPh3)]+, and Os(II)-thionitrosyl, [Os(II)(tpy)(Cl)2(NS)]+,
      complexes as products. The Os-N bond length and Os-N-P angle in cis
      [Os(IV)(tpy)(Cl)2(NPPh3)](PF6) are 2.077(6) A and 138.4(4) degrees. The rate law
      for formation of cis- and trans-[Os(IV)(tpy)(Cl)2(NPPh3)]+ is first order in both
      [Os(VI)(tpy)(Cl)2(N)]+ and SPPh3 with ktrans(25 degrees C, CH3CN) = 24.6 +/- 0.6
      M(-1) s(-1) and kcis(25 degrees C, CH3CN) = 0.84 +/- 0.09 M(-1) s(-1). As found
      earlier for [Os(II)(tpm)(Cl)2(NS)]+, both cis- and trans-[Os(II)(tpy)(Cl)2(NS)]+
      react with PPh3 to give [Os(IV)(tpy)(Cl)2(NPPh3)]+ and SPPh3. For both complexes,
      the reaction is first order in each reagent with ktrans(25 degrees C, CH3CN) =
      (6.79 +/- 0.08) x 10(2) M(-1) s(-1) and kcis(25 degrees C, CH3CN) = (2.30 +/-
      0.07) x 10(2) M(-1) s(-1). The fact that both reactions occur rules out
      mechanisms involving S atom transfer. These results can be explained by invoking
      a common intermediate, [Os(IV)(tpy)(Cl)2(NSPPh3)]+, which undergoes further
      reaction with PPh3 to give [Os(IV)(tpy)(Cl)2(NPPh3)]+ and SPPh3 or with
      [Os(VI)(tpy)(Cl)2(N)]+ to give [Os(IV)(tpy)(Cl)2(NPPh3)]+ and
      [Os(II)(tpy)(Cl)2(NS)]+.

PMID- 11232820
TI  - Multiple bonding in four-coordinated titanium(IV) compounds.
AB  - Theoretical description (MP2/6-311G* and B3LYP/6-311G*) is presented for
      hypovalent titanium alkoxide model compounds showing linear angleTi-O-C angles.
      This feature is explained by the existence of a polarized triple Ti-O bond. In
      contrast, a series of 18 electron germanium derivatives displaying bent angleGe-O
      C angles contain polarized single Ge-O bonds. The nature of the Ti-O and Ge-O
      bonds is established by means of natural bond order, atoms-in-molecules theory,
      and electron localization function analyses.

PMID- 11232821
TI  - Delocalized TCNQ stacks in nickel and copper tetraazamacrocyclic systems.
AB  - New derivatives of formula [M(dieneN4)](TCNQ)3, M = Ni or Cu and dieneN4 = cis-
      or trans-hexamethyltetraazacyclotetradecadiene, have been obtained. The TCNQ
      units show electronic delocalization and formation of 1D stacks, with no direct
      interactions with the metal cations. The stack is not uniform and can be seen as
      formed by trimeric dianions (TCNQ)3(2-). The electronic delocalization favors the
      conductivity in these materials, which behave as good semiconductors. The crystal
      structures of the trans derivatives have been solved: [Ni(transdieneN4)](TCNQ)3,
      triclinic, P-1, a = 8.809(2) A, b = 10.896(2) A, c = 13.727(2) A, alpha =
      103.04(1) degrees, beta = 101.23(2) degrees, gamma = 109.37(2) degrees, Z = 1;
      [Cu(trans-dieneN4)](TCNQ)3: triclinic, P-1, a = 7.872(1) A, b = 9.840(1) A, c =
      14.819(1) A, alpha = 92.32(1) degrees, beta = 95.05(1) degrees, gamma = 95.66(1)
      degrees, Z = 1.

PMID- 11232822
TI  - Oxo/sulfidotungstate(VI) as precursors to W(VI)O2, W(VI)OS, and W(VI)S2 complexes
      and W(IV)-dithiolene chelate rings.
AB  - Synthetic models leading to oxosulfidotungsten(VI) groups and dithiolene chelate
      rings have been investigated. The heterogeneous reaction systems [WO4-nSn]2
      /2Ph3SiCl/Me4phen (n = 0-2) in acetonitrile afford the complexes
      [WQ2(OSiPh3)2(Me4phen)] (1-3) in the indicated yields containing the groups
      W(VI)O2 (1; 86%), W(VI)O2 (2; 45%), and W(VI)S2 (3; 83%). In the crystalline
      state these complexes have imposed C2 symmetry, with cis-oxo/sulfido and trans
      silyloxide ligands. 1H NMR spectra indicate that this stereochemistry is retained
      in solution. The colors of 2 (yellow, 367 nm) and 3 (orange, 451 nm) arise from
      LMCT absorptions at the indicated wavelengths. These results demonstrate that the
      silylation procedure previously introduced for the preparation of molecules with
      the Mo(VI)OS group (Thapper, et al. Inorg. Chem. 1999, 38, 4104) extends to
      tungsten. Methods for the formation of dithiolene chelate rings MS2C2R2 in
      reactions with sulfide-bound M = Mo or W precursors are summarized. In a known
      reaction type, 3 and activated acetylenes rapidly form
      [W(IV)(OSiPh3)2(Me4phen)(S2C2R2)] (R = CO2Me, 4, 83%, and Ph, 5, 98%). In a new
      reaction type not requiring the isolation of an intermediate, the systems
      [MO2S2]2-/2Ph3SiCl/Me4phen/PhC=CPh in acetonitrile afford 5 (68%) and
      [Mo(IV)(OSiPh3)2(Me4phen)(S2C2Ph2)] (6; 61%). Complexes 5 and 6 are
      isostructural, maintain the trans-silyloxide stereochemistry, and exhibit chelate
      ring dimensions indicative of ene- 1,2-dithiolate coordination. Reductions in the
      -1.4 to -1.7 V range are described as metal-centered. It remains to be seen
      whether the oxo/sulfidotungsten(VI) groups in 1-3 eventuate in the active sites
      of tungstoenzymes. (Me4phen = 3,4,7,8-tetramethyl-1,10-phenanthroline.)

PMID- 11232823
TI  - Electrochemical studies of corrphycenes and metallocorrphycenes.
AB  - Corrphycene 3 (Cn) is a structural isomer of porphyrin 1 that was synthesized for
      the first time 5 years ago. This paper reports on the redox properties of free
      base octaethylcorrphycene H2OECn and 16 metal complexes derived therefrom. In
      CH2Cl2 solution, the free base and the metallo(II) octaethylcorrphycenes,
      M(II)OECn, typically undergo four distinct one-electron redox steps involving the
      tetrapyrrolic macrocycle, of which two are reduction steps and two are
      oxidations. One exception to this general pattern is displayed by the Co(II)OECn
      complex. In this instance, the first one-electron reduction is metal-centered and
      produces Co(I)OECn. A comparison of the redox potentials of corrphycenes with
      those of porphyrins and porphycenes indicates that the first reduction potentials
      of the free base and of the metallo-octaethylcorrphycenes are between those of
      the porphycenes-the easiest to reduce molecules in this set of isomeric
      tetrapyrrolic systems-and those of the porphyrins. The oxidation potentials of
      corrphycenes and porphyrins are found to be quite similar. On the other hand,
      porphycenes are oxidized at less positive potentials. The redox gap deltaE1/2 =
      E1/2Ox1 - E1/2Red1 is equal to 2.15 +/- 0.08 V for the free base corrphycene and
      the various metallocorrphycenes that were subjected to study. This redox gap is
      not much different from that observed in porphyrins (deltaE1/2 = 2.25 +/- 0.1 V),
      whereas if differs significantly from that observed in porphycenes (deltaE1/2 =
      1.85 +/- 0.15 V). The sequence of these deltaE1/2 values parallels the lowest
      energy absorption maxima observed in the UV-vis spectra of these three isomers.

PMID- 11232824
TI  - A monolayer complex of Cu2(OH)3C12H25SO4 directly precipitated from an aqueous
      SDS solution.
AB  - A layered complex with the chemical composition of Cu2(OH)3C12H25OSO3 was
      obtained through direct precipitation from a sodium dodecyl sulfate micellar
      solution of Cu(II) at a nearly neutral condition (pH approximately equals 6.8).
      From the XRD, 13C CPMAS NMR, and the spin probe ESR observations, a modified
      botallackite structure with a monolayer alkyl phase was proposed for the complex.
      Magnetic susceptibility measurements for the complex showed that there exist at
      least two exchange couplings: one is positive, and its magnitude is larger than
      that of the other, which is negative (J approximately equals -8 K). Although the
      cupric ions of the complex are paramagnetic, most of those are ESR silent and
      only the ESR signals from defects could be observed even at 298 K. A spin
      clustering model has been employed to explain the magnetic properties of the
      complex.

PMID- 11232825
TI  - Topological relationships and building blocks in Zintl phases of the composition
      Ba(n+1)(Mg,Li)2nSi2(n+1).
AB  - The structures of two novel Zintl phases, Ba6Mg5.2Li2.8Si12 and BaMg0.1Li0.9Si2,
      are presented. Both compounds contain chains in cis-trans conformation. The
      silicon partial structure of Ba6Mg5.2Li2.8Si12 (C2/m; a = 1212.0(1), b =
      459.78(4), c = 1129.10(9) pm; beta = 91.77(2) degrees; Z = 1) is built of
      unbranched, planar Si6 chains while BaMg0.1Li0.9Si2 (Pnma; a = 725.92(5), b =
      461.36(3), c = 1169.08(8) pm; Z = 4) consists of infinite Si(n) chains. The
      compounds show all electronic and structural characteristics that are typical for
      the special subset of Zintl phases with highly charged planar anions. The
      structures of the new compounds, as well as that of Ba2Mg3Si4, can be derived
      from the common parent type BaMg2Si2. It is shown that a comprehensive picture of
      a chemical twinning based on BaMg2Si2 can be derived.

PMID- 11232826
TI  - On the adiabaticity contribution to the rate of outer-sphere electron transfers.
      Reactions of cytochrome c and related transition metal compounds.
AB  - Magnetokinetic effects were observed between 0 and 8 T in electron-transfer
      reactions of Ru(bipy)3(3+) with ferrous cytochrome c, Fe(bipy)3(2+), Fe(Me4
      [14]1,3,8,10-tetraene-1,4,8,11-N4)(solvent)2(2+), and Ru(NH3)6(2+). The effects
      have been related to the adiabatic character of the reactions and rationalized in
      terms of a mechanism that incorporates the spin-orbit coupling, hyperfine
      coupling, and Zeeman mechanism in the expression of the reaction rate constant.

PMID- 11232827
TI  - Crystal structure of bis(4-methylimidazole)tetraphenylporphyrinatoiron(III)
      chloride and related compounds. Correlation of ground state with Fe-N bond
      lengths.
AB  - The crystal structure of the title compound is presented and shown to be one of a
      class of low-spin iron porphyrin complexes having a ground-state electronic
      configuration of (dxy)2(dxz)2(dyz)1. If their Fe-N bond lengths (average N
      porphyrin plotted against average N-axial) are considered, this class of low-spin
      iron(III) porphyrins of general formula [Fe(III)Por(L)2]+X- and of 2B ground
      state is shown to be distinctly different crystallographically from a similar
      class of compounds with the same general formula but with a 2E or a
      (dxy)2(dxz,dyz)3 ground state. A third group of compounds with the same general
      formula have a (dxz,dyz)4(d)1 ground state and again are in a different region of
      the plot. Compounds showing intermediate properties can be forecast from the
      simple relationship presented in this work. The electron paramagenetic resonance
      data are shown to be dependent on the ground state, and those of configuration
      (dxy)2(dxz,dyz)3 and the 2B ground state obey a correlation previously suggested
      in the literature.

PMID- 11232828
TI  - Helical-chain copper(II) complexes and a cyclic tetranuclear copper(II) complex
      with single syn-anti carboxylate bridges and ferromagnetic exchange interactions.
AB  - Tridentate Schiff-base carboxylate-containing ligands, derived from the
      condensation of 2-imidazolecarboxaldehyde with the amino acids beta-alanine
      (H2L1) and 2-aminobenzoic acid (H2L5) and the condensation of 2
      pyridinecarboxaldehyde with beta-alanine (HL2), D,L-3-aminobutyric acid (HL3),
      and 4-aminobutyric acid (HL4), react with copper(II) perchlorate to give rise to
      the helical-chain complexes [[Cu(mu-HL1)(H2O)](ClO4)]n (1), [[Cu(mu
      L2)(H2O)](ClO4).2H2O]n (2), and [[Cu(mu-L3)(H2O)](ClO4).2H2O]n (3), the
      tetranuclear complex [[Cu(mu-L4)(H2O)](ClO4)]4 (4), and the mononuclear complex
      [Cu(HL5)(H2O)](ClO4).1/2H2O (5). The reaction of copper(II) chloride with H2L1
      leads not to a syn-anti carboxylate-bridged compound but to the chloride-bridged
      dinuclear complex [Cu(HL1)(mu-Cl)]2 (6). The structures of these complexes have
      been solved by X-ray crystallography. In complexes 1-4, roughly square-pyramidal
      copper(II) ions are sequentially bridged by syn-anti carboxylate groups.
      Copper(II) ions exhibit CuN2O3 coordination environments with the three donor
      atoms of the ligand and one oxygen atom belonging to the carboxylate group of an
      adjacent molecule occupying the basal positions and an oxygen atom (from a water
      molecule in the case of compounds 1-3 and from a perchlorate anion in 4)
      coordinated in the apical position. Therefore, carboxylate groups are mutually
      cis oriented and each syn-anti carboxylate group bridges two copper(II) ions in
      basal-basal positions with Cu...Cu distances ranging from 4.541 A for 4 to 5.186
      A for 2. In complex 5, the water molecule occupies an equatorial position in the
      distorted octahedral environment of the copper(II) ion and the Cu-O carboxylate
      distances in axial positions are very large (>2.78 A). Therefore, this complex
      can be considered as mononuclear. Complex 6 exhibits a dinuclear parallel planar
      structure with Ci symmetry. Copper(II) ions display a square-pyramidal
      coordination geometry (tau = 0.06) for the N2OCl2 donor set, where the basal
      coordination sites are occupied by one of the bridging chlorine atoms and the
      three donor atoms of the tridentate ligand and the apical site is occupied by the
      remaining bridging chlorine atom. Magnetic susceptibility measurements indicate
      that complexes 1-4 exhibit weak ferromagnetic interactions whereas a weak
      antiferromagnetic coupling has been established for 6. The magnetic behavior can
      be satisfactorily explained on the basis of the structural data for these and
      related complexes.

PMID- 11232829
TI  - Molecular structures and magnetic properties of the mixed-ligand complexes of
      bis(hexafluoroacetylacetonato)manganese(II), -copper(II), and -zinc(II) with 4,4'
      bis(N-tert-butyl-N-oxylamino)-2,2'-bipyridine. Isosceles triangular hetero-three
      spin systems consisting of aminoxyls and metal ions.
AB  - 4,4'-Bis(N-tert-butyloxylamino)-2,2'-bipyridine (4) and its 1:1 complexes with
      bis(hexafluoroacetylacetonato)manganese(II), -copper(II), and -zinc(II) were
      prepared. An X-ray structure analysis of free ligand 4 reveals that the molecule
      has a trans conformation with Ci symmetry and the aminoxyl radical center has a
      short contact of 2.36 A with one of the neighboring molecules. The three 1:1
      complexes have mutually similar molecular structures in which the 2,2'-bipyridine
      moiety has a cis conformation and serves as a bidentate ligand and coordination
      geometry around the metal atom is a distorted octahedron. The EPR experiments for
      free ligand 4 and [Zn(hfac)2.4] in frozen solution suggested that the exchange
      couplings between the two aminoxyls (R) through the 2,2'-bipyridine rings are
      antiferromagnetic with JR-R/kB = -19.3 +/- 0.5 and -24.3 +/- 0.4 K, respectively.
      Isosceles triangular three-spin models were applied to the 1:1 magnetic metal
      complexes to give JR-M/kB = -19.1 +/- 0.2 K and JR-R/kB = -32.9 +/- 0.3 K for
      [Mn(hfac)2.4] and JR-M/kB = +73 +/- 18 K and JR-R/kB = -24.5 +/- 6.5 K for
      [Cu(hfac)2.4].

PMID- 11232830
TI  - Effect of conformational constraints on gated electron-transfer kinetics. 3.
      Copper(II/I) complexes with cis- and trans-cyclopentanediyl-1,4,8,11
      tetrathiacyclotetradecane.
AB  - Previous kinetic and electrochemical studies of copper complexes with macrocyclic
      tetrathiaethers-such as 1,4,8,11-tetrathiacyclotetradecane ([14]aneS4)-have
      indicated that electron transfer and the accompanying conformational change occur
      sequentially to give rise to a dual-pathway mechanism. Under appropriate
      conditions, the conformational change itself may become rate-limiting, a
      condition known as "gated" electron transfer. We have recently hypothesized that
      the controlling conformational change involves inversion of two donor atoms,
      which suggests that "gated" behavior should be affected by appropriate steric
      constraints. In the current work, two derivatives of [14]aneS4 have been
      synthesized in which one of the ethylene bridges has been replaced by either cis-
      or trans-1,2-cyclopentane. The resulting copper systems have been characterized
      in terms of their Cu(II/I)L potentials, the stabilities of their oxidized and
      reduced complexes, and their crystal structures. The electron self-exchange rate
      constants have been determined both by NMR line-broadening and by kinetic
      measurements of their rates of reduction and oxidation with six or seven counter
      reagents. All studies have been carried out at 25 degrees C, mu = 0.10 M (NaClO4
      and/or Cu(ClO4)2), in aqueous solution. Both Cu(II/I) systems show evidence of a
      dual-pathway mechanism, and the electron self-exchange rate constants
      representative of both mechanistic pathways have been determined. The first-order
      rate constant for gated behavior has also been resolved for the Cu(I)(trans
      cyclopentane-[14]aneS4) complex, but only a limiting value can be established for
      the corresponding cis-cyclopentane system. The rate constants for both systems
      investigated in this work are compared to values previously determined for the
      Cu(II/I) systems with the parent [14]aneS4 macrocycle and its derivatives
      involving phenylene and cis- or trans-cyclohexane substituents. The results are
      discussed in terms of the influence of the fused rings on the probable
      conformational changes accompanying the electron-transfer process.

PMID- 11232831
TI  - Chemical applications of topology and group theory. 34. Structure and bonding in
      titanocarbohedrene cages.
AB  - Chemical bonding models are developed for the titanocarbohedrenes Ti14C13 and
      Ti8C12 by assuming that the Ti atoms use a six-orbital sd5 manifold and there is
      no direct Ti...Ti bonding. In the 3 x 3 x 3 cubic structure of Ti14C13, the 8 Ti
      atoms at the vertices of the cube are divided into two tetrahedral sets, one
      Ti(III) set and one Ti(IV) set, and the 6 Ti atoms at the midpoints of the cube
      faces exhibit square planar TiC4 coordination with two perpendicular three-center
      four-electron bonds. The energetically unfavorable Th dodecahedral structure for
      Ti8C12 has 8 equivalent Ti(III) atoms and C2(4-) units derived from the complete
      deprotonation of ethylene. In the more energetically favorable Td tetracapped
      tetrahedral structure for Ti8C12, the C2 units are formally dianions and the 8 Ti
      atoms are partitioned into inner tetrahedra (Ti(i)) bonded to the C2 units
      through three-center Ti-C2 bonds and outer tetrahedra (Ti degrees) bonded to the
      C2 units through two-center Ti-C bonds. The Ti atoms in one of the Ti4 tetrahedra
      are Ti(0) and those in the other Ti4 tetrahedron are Ti(III). Among the two such
      possibilities, the lower energy form has the (Ti0)o4(Ti(III))i4 configuration,
      corresponding to dicarbene C2 ligands with two unpaired electrons in the carbon
      carbon pi-bonding similar to the multiple bond in triplet O2. This contrasts with
      the opposite (Ti(III)o4(Ti0)i4 configuration in the higher energy form of Th
      Ti8C12, corresponding to ethynediyl ligands with full C...C triple bonds and
      unpaired electrons in the C sp hybrid orbitals for sigma-bonding to Ti.

PMID- 11232832
TI  - Chemical properties of the Pd4(dppm)4(H)2(2+) cluster and the homogeneous
      electrocatalytical behavior of hydrogen evolution and formate decomposition.
AB  - Two new reductive electrochemical (CO2 + H2O + 2e-; HCO2H + 2e-) and two new
      chemical methods (Al(CH3)3 + proton donor; NaO2CH) to prepare the title compound
      from Pd2(dppm)2Cl2 are reported. For the latter method, an intermediate species
      formulated as Pd2(dppm)4(O2CH)2(2+) is identified spectroscopically (1H NMR, 31P
      NMR, IR, and FAB-MS). Limited stability of the title compound in the presence of
      Cl- and Br- as counteranions is noticed and is due to sensitivity of the cluster
      toward nucleophilic attack of the halide ions. This result is corroborated by the
      rapid decomposition of these clusters in the presence of CN- to form the
      binuclear species Pd2(dppm)2(CN)4 and by the preparation of the stable salts
      [Pd4(dppm)4(H)2](X)2(X- = BF4-, PF6-, BPh4-). Upon a two-electron electrochemical
      reduction of this cluster to the neutral species (E1/2 = -1.42 V vs SCE in DMF)
      in the presence of 1 equiv of HCO2H, a highly reactive species formulated as
      [Pd4(dppm)4(H)3]+ is generated and characterized by 1H NMR, 31P NMR, and cyclic
      voltammetry. Subsequent addition of H+ (via RCO2H; R = H, CH3, CF3, C6H5) under
      the same reducing conditions, induces the homogeneous catalysis of H2 evolution.
      The turnover number is found to be 134 in 2 h, with no evidence for catalyst
      decomposition. This same species also exhibits a one-electron oxidation process
      (E1/2 = -0.61 V vs SCE in DMF) that induces the catalytical decomposition of
      formate (HCO2- --> CO2 + 1/2H2 + 1e-). This double catalysis from the same
      cluster intermediate is unprecedented.

PMID- 11232833
TI  - Sandwich-type silicotungstates: structure and magnetic properties of the dimeric
      polyoxoanions[[SiM2W9O34(H2O)]2]12- (M = Mn2+, Cu2+, Zn2+).
AB  - The novel dimeric silicotungstates [[SiM2W9O34(H2O)]2]12- (M = Mn2+, Cu2+, Zn2+)
      have been synthesized and characterized by IR spectroscopy, elemental analysis,
      and magnetic measurements. X-ray single-crystal analyses were carried out on
      K4Na6Mn[[SiMn2W9O34(H2O)]2].33H2O (1), which crystallizes in the triclinic
      system, space group P1, with a = 12.2376(7) A, b = 13.6764(8) A, c = 15.6177(9)
      A, alpha = 70.2860(10) degrees, beta = 79.9150(10) degrees, gamma = 70.2760(10)
      degrees, and Z = 1; K3Na5[[SiCu2W9O34(H2O)]2].26H2O (2) crystallizes in the
      triclinic system, space group P1, with a = 11.4271(12) A, b = 12.5956(13) A, c =
      15.3223(16) A, alpha = 80.456(2)degrees, beta = 76.383(2) degrees, gamma =
      76.968(2) degrees, and Z = 1; K4Na6[[SiZn2W9O34(H2O)]2].34H2O (3) crystallizes
      also in the triclinic system, space group P1, with a = 12.2596(14) A, b =
      13.2555(15) A, c = 16.2892(18) A, alpha = 96.431(2) degrees, beta = 100.944(2)
      degrees, gamma = 110.404(2) degrees, and Z = 1. The polyanions consist of two
      lacunary B-alpha-[SiW9O34]10- Keggin moieties linked via a rhomblike M4O16 (M =
      Mn, Cu, Zn) group leading to a sandwich-type structure. Magnetic measurements
      show that the central Mn4 unit in 1 exhibits antiferromagnetic (J = -1.77(5) cm(
      1)) as well as weak ferromagnetic (J' = 0.08(2) cm(-1)) Mn-Mn exchange
      interactions. In 2 the Cu-Cu exchange interactions are antiferromagnetic (J = 
      0.10(2) cm(-1), J' = -0.29(2) cm(-1)).

PMID- 11232834
TI  - Theoretical models for the oxygen radical mechanism of water oxidation and of the
      water oxidizing complex of photosystem II.
AB  - Hybrid density functional theory is used to study reasonably realistic models of
      the oxygen-evolving manganese complex in photosystem II. Since there is not yet
      any X-ray structure of the complex, other types of experimental and theoretical
      information are used to construct the model complexes. In these complexes, three
      manganese centers are predicted to be closely coupled by mu-oxo bonds in a
      triangular orientation. Using these models, the previously suggested oxygen
      radical mechanism for O2 formation is reinvestigated. It is found that the oxygen
      radical in the S3 state now appears in a bridging position between two manganese
      atoms. It is still suggested that only one manganese atom is redox-active.
      Instead, a number of surprisingly large trans-effects are found, which motivate
      the existence and define the function of the other manganese atoms in the Mn4
      cluster. Calcium has a strong chelating effect which helps in the creation of the
      necessary oxygen radical. In the present model the chemistry preceding the actual
      O-O bond formation occurs in an incomplete cube with a missing corner and with
      two manganese and one calcium in three of the corners. The external water
      providing the second oxygen of O2 enters in the missing corner of the cube. The
      present findings are in most cases in good agreement with experimental results as
      given in particular by EXAFS.

PMID- 11232835
TI  - Molecular and electronic structures of bis(pyridine-2,6-diimine)metal complexes
      [ML2](PF6)n (n = 0, 1, 2, 3; M = Mn, Fe, Co, Ni, Cu, Zn).
AB  - A series of mononuclear, octahedral first-row transition metal ion complexes mer
      [M(II)L0(2)](PF6)2 containing the tridentate neutral ligand 2,6-bis[1-(4
      methoxyphenylimino)ethyl]pyridine (L0) and a Mn(II), Fe(II), Co(II), Ni(II),
      Cu(II), or Zn(II) ion have been synthesized and characterized by X-ray
      crystallography. Cyclic voltammetry and controlled potential coulometry show that
      each dication (except those of Cu(II) and Zn(II)) can be reversibly one-electron
      oxidized, yielding the respective trications [M(III)L0(2)]3+, and in addition,
      they can be reversibly reduced to the corresponding monocations [ML2]+ and the
      neutral species [ML2]0 by two successive one-electron processes. [MnL2]PF6 and
      [CoL2]PF6 have been isolated and characterized by X-ray crystallography; their
      electronic structures are described as [Mn(III)L1(2)]PF6 and [Co(I)L0(2)]PF6
      where (L1)1- represents the one-electron-reduced radical form of L0. The
      electronic structures of the tri-, di-, and monocations and of the neutral
      species have been elucidated in detail by a combination of spectroscopies: UV
      vis, NMR, X-band EPR, Mossbauer, temperature-dependent magnetochemistry. It is
      shown that pyridine-2,6-diimine ligands are noninnocent ligands that can be
      coordinated to transition metal ions as neutral L0 or, alternatively, as
      monoanionic radical (L1)1-. All trications are of the type [M(III)L0(2)]3+, and
      the dications are [M(II)L0(2)]2+. The monocations are described as
      [Mn(III)L1(2)]+ (S = 0), [Fe(II)L0L1]+ (S = 1/2), [Co(I)L0(2)]+ (S = 1),
      [Ni(I)L0(2)]+ (S = 1/2), [Cu(I)L0(2)]+ (S = 0), [Zn(II)L1L0]+ (S = 1/2) where the
      Mn(II) and Fe(II) ions are low-spin-configurated. The neutral species are
      described as [Mn(II)L1(2)]0, [Fe(II)L1(2)]0, [Co(I)L0L1]0, [Ni(I)L0L1]0, and
      [Zn(II)L1(2)]0; their electronic ground states have not been determined.

PMID- 11232836
TI  - Electrochemistry in benzotrifluoride: redox studies in a "noncoordinating"
      solvent capable of bridging the organic and fluorous phases.

PMID- 11232838
TI  - Synthesis and structure of dimeric silver azooximates. Hydrogen bonding and
      nonbonded Ag...Ag interaction.

PMID- 11232839
TI  - Reactivity of Pd(0) complexes with the phosphino ylide [Ph2PCH2PPh2=C(H)C(O)Me].
      Molecular structure of [Pd(PPh2CHPPh2C(H)C(O)Me)2].

PMID- 11232840
TI  - High-performance liquid chromatographic determination for bile components in
      fish, chicken and duck.
AB  - A HPLC procedure for the determination of 13 bile acids and cyprinol sulfate in
      animals was developed. The mobile system 0.3% ammonium carbonate solution
      acetonitrile (73:27, v/v) 10 min-->(68:32) 10 min-->(50:50) 10 min was available
      for separating all 14 bile components, except for deoxycholic and
      glycodeoxycholic acids, which could be further separated with 0.3% ammonium
      carbonate solution-acetonitrile (73:27). After applying this method, grass carp
      and common carp bile was found to contain mainly cyprinol sulfate, while the
      other 12 fish species bile contained mainly taurocholic, taurochenodeoxycholic
      and cholic acids. Chicken bile was mainly composed of glycolithocholic and
      taurocholic acids, but duck bile was mainly composed of taurochenodeoxycholic,
      cholic and ursodeoxycholic acids.

PMID- 11232841
TI  - High-performance liquid chromatographic assays for a second-generation novel oral
      iron chelator (APCP363) and their application to pharmacokinetic studies in rats.
AB  - Sensitive and specific HPLC assays for APCP363 in biological matrices (rat
      plasma, urine and feces) were developed. The recovery of APCP363 ranged from 81.2
      to 99.9% in plasma, from 82.1 to 92.8% in urine, and from 65 to 68% in feces.
      Standard deviations were below 10% for all analyses. The limits of quantitation
      were 0.1, 10 and 30 microg/ml in plasma, urine and feces, respectively. The HPLC
      assays, which are the first reports for APCP363 analysis in biological matrices,
      have been successfully applied to preliminary pharmacokinetic studies in rats.
      The stool assay is the first non-radiolabeled method for hydroxypyridinones in
      feces.

PMID- 11232842
TI  - Properties of a stationary phase based on immobilised chicken liver basic fatty
      acid-binding protein.
AB  - The fatty acid-binding proteins (FABPs) are a class of low-molecular-mass
      proteins that bind fatty acids and are thought to be involved in their
      intracellular transport. FABPs have been isolated and studied from several
      tissues, but their precise function and mechanism of action are still not clear.
      Chicken liver (basic) fatty acid-binding protein (bFABP) was immobilised on
      aminopropyl silica and the developed stationary phase was used to examine the
      enantioselective properties of this protein and to study the binding of drugs to
      bFABP. The retention and enantioselectivity of the new column for a large number
      of chiral drugs was investigated. The enantiomers of basic and neutral compounds
      were poorly retained and not resolved by the bFABP column. On the contrary the
      resolution of the enantiomers of some acidic compounds was obtained. Therefore
      the influence of the mobile phase pH and organic modifier on the chromatographic
      performance of acidic compounds was studied. In order to clarify the retention
      mechanism, competitive displacement studies were also carried out by adding short
      chain fatty acids to the mobile phase as displacing agents and preliminary
      quantitative structure-retention relationship correlations were developed to
      describe the nature of the interactions between the chemical structures of the
      analytes and the observed chromatographic results.

PMID- 11232843
TI  - Sedimentation field-flow fractionation device cleaning, decontamination and
      sterilization procedures for cellular analysis.
AB  - In Sedimentation FFF (SdFFF) practice, it is known that a large number of cell
      elutions create aging phenomena of the separator, thereby reducing recovery and
      modifying elution characteristics. Systematic cleaning procedures are developed
      to enhance channel lifetime, together with microbial decontamination processes.
      Cells can be therefore reproducibly eluted for a large number of analyses and
      collected under sterile conditions, if needed. This is one of the most valuable
      aspect if further culture or transplantation is required. Decontamination was
      performed using, as contaminant probe, Staphylococcus aureus, highly adherent
      pathogenic bacteria that eluted from SdFFF as aggregates.

PMID- 11232844
TI  - Electron-capture gas chromatographic-chemical ionization mass spectrometric study
      of sera from people vaccinated with bacille Calmette-Guerin for characteristic
      metabolites.
AB  - Serum samples from 26 individuals vaccinated with bacille Calmette-Guerin (BCG)
      and from 26 controls (10 patients with pulmonary tuberculosis and 16 non BCG
      vaccinated healthy individuals) were analyzed by frequency-pulsed electron
      capture gas chromatography (FPEC-GC) and chemical ionization gas chromatography
      mass spectrometry (CIGC-MS) for the presence of characteristic metabolites. A
      distinct pattern consisted of tuberculostearic acid (TSA) and a peak, labeled
      peak 1, was observed in all BCG-vaccinated individuals, whereas only three of 26
      controls generated this chromatography profile. TSA was detected in all patients
      with pulmonary tuberculosis but peak 1 was absent. Sera drawn from 12 individuals
      11 to 14 days after BCG vaccination yielded three transitional FPEC-GC profiles.
      A permanent FPEC-GC profile consisting of TSA and of a full scale peak 1 appeared
      28 days to a few months after BCG vaccination. Peak 1 was tentatively identified
      by CIGC-MS as 9-methyl-hexacosanol. The findings suggest that peak 1 may serve as
      a marker to detect Mycobacterium bovis BCG and to distinguish individuals
      infected with M. tuberculosis from individuals vaccinated with BCG.

PMID- 11232845
TI  - Determination of the human salivary peptides histatins 1, 3, 5 and statherin by
      high-performance liquid chromatography and by diode-array detection.
AB  - A reversed-phase high-performance liquid chromatography (HPLC) method with diode
      array detection for the quantification of several human salivary peptides is
      described. Sample pretreatment consisted of the acidification of whole saliva by
      phosphate buffer. This treatment produced precipitation of mucins, alpha-amylases
      and other high-molecular-mass salivary proteins, simultaneous inhibition of
      intrinsic protease activities and reduction of sample viscosity. Direct HPLC
      analysis by diode-array detection of the resulting acidic sample allowed one to
      quantify histatin 1, histatin 3, histatin 5, statherin, as well as uric acid, in
      normal subjects. Moreover, the groups of peaks pertaining to proline-rich
      proteins and cystatins were tentatively identified. The method can be useful in
      assessing the concentration of salivary peptides from normal subjects and from
      patients suffering oral and/or periodontal diseases.

PMID- 11232846
TI  - Anion-exchange high-performance liquid chromatography assays of plasma
      lipoproteins and modified low-density lipoproteins using a ProtEx-DEAE column.
AB  - Previously [Anal. Biochem., 232 (1995) 163-171], we reported a high-performance
      liquid chromatography (HPLC) assay method for human plasma lipoproteins using a
      diethylaminoethyl (DEAE)-glucomannan column, which is not commercially available.
      In this study, HPLC assay methods for lipoproteins in plasma samples of human and
      experimental animals, and modified low-density lipoproteins (LDLs) of rabbits
      have been developed using a commercially available anion-exchange ProtEx-DEAE
      column. For the assays of plasma lipoproteins, the method includes complete
      separation of high-density lipoproteins, LDLs and very low-density lipoproteins
      within 20 min using stepwise elution, and determination by post-column reaction
      with an enzymatic cholesterol reagent as the total cholesterol (TC) level.
      Similarly, mild oxidative and artificially oxidised LDLs were separated into
      their subfractions using stepwise elution, and determined based on the TC level.
      The methods using the DEAE-glucomannan and ProtEx-DEAE columns were cross
      validated. There was an excellent correlation between the two methods. The
      obtained results reveal that the anion-exchange HPLC method using the ProtEx-DEAE
      column could be useful for the assays of plasma lipoproteins and modified LDLs.

PMID- 11232847
TI  - High-performance liquid chromatographic determination of the beta2-selective
      adrenergic agonist fenoterol in human plasma after fluorescence derivatization.
AB  - A sensitive high-performance liquid chromatographic method has been developed for
      the determination of the beta2-selective adrenergic agonist fenoterol in human
      plasma. To improve the sensitivity of the method, fenoterol was derivatized with
      N-(chloroformyl)-carbazole prior to HPLC analysis yielding highly fluorescent
      derivatives. The assay involves protein precipitation with acetonitrile, liquid
      liquid-extraction of fenoterol from plasma with isobutanol under alkaline
      conditions followed by derivatization with N-(chloroformyl)-carbazole. Reversed
      phase liquid chromatographic determination of the fenoterol derivative was
      performed using a column-switching system consisting of a LiChrospher 100 RP 18
      and a LiChrospher RP-Select B column with acetonitrile, methanol and water as
      mobile phase. The limit of quantitation in human plasma was 376 pg fenoterol/ml.
      The method was successfully applied for the assay of fenoterol in patient plasma.

PMID- 11232848
TI  - Column-switching high-performance liquid chromatography-electrospray ionization
      mass spectrometry for identification of heroin metabolites in human urine.
AB  - In order to prove heroin (DAM) use, a simple, rapid and sensitive analytical
      method has been established by combining semi-microcolumn HPLC, a column
      switching technique and electrospray ionization mass spectrometry (ESI-MS). Urine
      samples were directly introduced to the system, and endogenous urinary
      constituents were removed by using on-line column switching solid-phase
      extraction with a strong cation-exchange (SCX) cartridge column (2.0 mm I.D. x 10
      mm). Heroin and its metabolites enriched on the top of the column were then
      successfully analyzed with excellent separation by use of a SCX semi-microcolumn
      (1.5 mm I.D. x 150 mm), accompanied by ESI mass spectral detection. The proposed
      conditions are as follows: mobile phase, 10 mM ammonium acetate (pH 6.0)
      acetonitrile (30:70, v/v) (for main separation) and 30 mM ammonium acetate (for
      trapping); flow-rates, 120 microl/min (for main separation) and 200 microl/min
      (for trapping); capillary voltage, +4.5 kV; cone voltage, 50 V. Linear
      calibration curves were obtained in the selected ion monitoring (SIM) mode using
      protonated molecular ions (m/z 370 for DAM, m/z 328 for MAM and m/z 286 for MOR)
      over the concentration ranges from 10 to 1000 ng/ml for morphine (MOR) and 1-100
      ng/ml for DAM and 6-acetylmorphine (MAM). The detection limits were 0.1-3 ng/ml.
      Upon applying the scan mode, 2-30 ng/ml were the detection limits. The present
      HPLC-ESI-MS method was successfully applied to the determination of opiates in
      users' urine samples.

PMID- 11232850
TI  - Analysis of cocaethylene, benzoylecgonine and cocaine in human urine by high
      performance thin-layer chromatography with ultraviolet detection: a comparison
      with high-performance liquid chromatography.
AB  - Cocaine and ethanol are frequently used at the same time, resulting in the
      formation of cocaethylene by transesterification. We studied the capability of
      high-performance thin-layer chromatography (HPTLC) to simultaneously detect
      cocaethylene, cocaine and benzoylecgonine in 16 urine specimens of drug addicts,
      previously tested as positive for benzoylecgonine at immunoenzymatic screening.
      Accuracy and precision, as well as detection and quantitation limits of the
      method, were evaluated by comparison with high-performance liquid chromatography
      (HPLC). HPTLC limit of quantitation was 1.0 microg/ml for the three compounds,
      whereas HPLC limits were 0.2 microg/ml for benzoylecgonine and cocaine, and 0.1
      microg/ml for cocaethylene. The relative standard deviation (RSD) ranged from
      1.03 to 12.60% and from 1.56 to 16.6% for intra- and inter-day HPTLC analysis,
      respectively. In the case of the HPLC method, the RSD for the intra-day precision
      ranged from 0.79 to 5.05%, whereas it ranged from 1.19 to 10.64% for the inter
      day precision. In comparison with HPLC, HPTLC is less expensive and faster,
      requiring 2-3 h to analyze 10-12 samples on a single plate. In conclusion, HPTLC
      is suitable for determinations of the three analytes only for samples with high
      concentrations.

PMID- 11232849
TI  - Simultaneous determination of inulin and p-aminohippuric acid in plasma and urine
      by reversed-phase high-performance liquid chromatography.
AB  - A simple, accurate and sensitive high-performance liquid chromatographic method
      with UV detection was carried out to measure simultaneously plasma and urine
      concentrations of both p-aminohippuric acid and inulin. Following a simplified
      acid hydrolysis of the sample, the separation was carried out in 4 min using a
      C18 reversed-phase column with a flow-rate of 1 ml/min, and monitoring the
      absorbance at 280 nm. Within the investigated concentration ranges of inulin (0.1
      3.2 mg/ml) and p-aminohippuric acid (0.0097-0.3 mg/ml), good linearity (r>0.99)
      was obtained. Within-run RSD ranged from 2.9 to 6.1% and between-run RSD ranged
      from 6.4 to 10%. Analytical recoveries were 101-112%, with little differences
      between plasma and urine samples. The detection limit was 1 microg/ml for all the
      analytes studied. This method might be ideal for renal function studies where a
      rapid and reproducible assessment of both renal glomerular filtration rate and
      blood flow-rate is required.

PMID- 11232851
TI  - Influence of citrate and EDTA anticoagulants on plasma malondialdehyde
      concentrations estimated by high-performance liquid chromatography.
AB  - Estimation of lipid peroxidation through MDA formation measured by assaying
      thiobarbituric acid (TBA) reactive products separated by HPLC remains the method
      of choice to study the development of oxidative stress in blood plasma. In this
      report we describe the influence of citrate and EDTA anticoagulants used for
      blood collection on estimation of MDA concentrations using HPLC analysis of MDA
      TBA adducts. We analyzed a group of 40 blood donors (21 men and 19 women), median
      age 27 years, range 19-48 years. The mean MDA concentration in citrate plasma was
      1.43+/-0.51 micromol/l (range: 0.61-2.57 micromol/l) and in EDTA plasma 0.36+/
      0.10 micromol/l (range: 0.13-0.63 micromol/l). There was a significant difference
      in MDA mean concentration that we attribute to different antioxidant properties
      of anticoagulants used for blood collection. Consistency in the choice of
      anticoagulant is clearly extremely important.

PMID- 11232852
TI  - Modified method for determination of hippuric acid and methylhippuric acid in
      urine by gas chromatography.
AB  - A modified method for the simultaneous determination of hippuric acid (HA) and o
      , m- and p-methylhippuric acids (o-, m- and p-MHAs) in urine is described. These
      metabolites were extracted, derivatized into their methyl ester derivatives and
      analyzed using a gas chromatograph equipped with flame ionization detector and a
      DB-1 capillary column. The derivatives of HA, o-, m- and p-MHAs were well
      separated within 11 min. The accuracy and precision in the present method were
      sufficient for quantitative analysis, and the results obtained by the GC method
      were highly correlated with those by the HPLC method (NIOSH 8301).

PMID- 11232853
TI  - Analytical control of a pharmaceutical formulation of sodium picosulfate by
      capillary zone electrophoresis.
AB  - A new procedure for the analytical control of a pharmaceutical formulation by
      capillary zone electrophoresis (CZE) is proposed. It allows the simultaneous
      determination of the major compounds in the formulation: active compound (sodium
      picosulfate) and preservative (methylparaben), and the degradation products of
      the preservative, which slowly degrades by hydrolysis or by transesterification
      with sorbitol (sweetener in excess in the formulation) yielding p-hydroxybenzoic
      acid and sorbitolparaben, respectively. UV-Vis detection in the absorption maxima
      of the analytes and 20 mM borate solution at pH 10 as background electrolyte are
      used. Results are compared with those provided by the HPLC procedure. The method
      has also been validated using the HPLC procedure as the reference method,
      evaluating selectivity, accuracy, linearity and precision. The CZE procedure
      developed is sufficiently accurate and the precision achieved is about 1% for
      major and 3% for minor compounds.

PMID- 11232854
TI  - Distribution of the hallucinogens N,N-dimethyltryptamine and 5-methoxy-N,N
      dimethyltryptamine in rat brain following intraperitoneal injection: application
      of a new solid-phase extraction LC-APcI-MS-MS-isotope dilution method.
AB  - A method for the solid-phase extraction (SPE) and liquid chromatographic
      atmospheric pressure chemical ionization-mass spectrometric-mass spectrometric
      isotope dilution (LC-APcI-MS-MS-ID) analysis of the indole hallucinogens N,N
      dimethyltryptamine (DMT) and 5-methoxy DMT (or O-methyl bufotenin, OMB) from rat
      brain tissue is reported. Rats were administered DMT or OMB by the
      intraperitoneal route at a dose of 5 mg/kg and sacrificed 15 min post treatment.
      Brains were dissected into discrete areas and analyzed by the methods described
      as a demonstration of the procedure's applicability. The synthesis and use of two
      new deuterated internal standards for these purposes are also reported.

PMID- 11232855
TI  - A high-performance liquid chromatography-tandem mass spectrometric method for the
      determination of pharmacokinetics of ganaxolone in rat, monkey, dog and human
      plasma.
AB  - A method for determining concentration levels of ganaxolone in rat, monkey, dog
      and human plasma was validated in the range of 5-1500 ng/ml using a 200-microl
      plasma sample volume. This validation report describes the linearity,
      specificity. sensitivity, reproducibility, accuracy, recovery and stability of
      the analytical method. The inter-day C.V. ranged from 0.5 to 9.2%, intra-day C.V.
      from 0.7 to 8.8% and intra-day accuracy (mean absolute percentage difference)
      ranged from 0.0 to 14.0% for rat, monkey, dog and human plasma. The method was
      used for the routine analysis of ganaxolone in rat, monkey, dog and human plasma
      and summary of the pharmacokinetic data are presented.

PMID- 11232856
TI  - New high-performance liquid chromatographic method for the detection of picolinic
      acid in biological fluids.
AB  - A HPLC method is described to quantify picolinic acid in milk, blood serum and
      tissue culture supernatant. The method requires very little sample preparation
      because acid precipitation allows total recovery of picolinic acid. High
      specificity and sensitivity were obtained using ion-pair chromatography on a C18
      reversed-phase column with tetrabutylammonium hydrogen sulfate as ion pairing
      reagent. We describe the conditions for the automated testing of multiple samples
      and for the detection of L-tryptophan and L-kynurenine together with picolinic
      acid. This system will be utilized to elucidate the relationship between
      picolinic acid production and human disease. Furthermore, we provide the first
      evidence of picolinic acid in human blood serum.

PMID- 11232858
TI  - Development of a high-performance liquid chromatographic method for
      bioequivalence study of flavoxate tablets.
AB  - An improved HPLC method was developed for the concentration determination of the
      metabolite of flavoxate, 3-methyl-flavone-8-carboxylic acid (MFCA), in plasma in
      an attempt to compare two flavoxate tablet formulations. This HPLC method was
      validated by examining the precision and the accuracy for inter-day and intra-day
      runs in a linear concentration range of 0.1-24 microg/ml. The coefficients of
      variation (C.V.) of inter-day and intra-day assays were 0.24-7.18% and 0.06
      5.70%, respectively. The standard errors of mean (S.E.M.) were -0.004-8.68% and 
      2.52-4.86% for inter-day and intra-day assays, respectively. Bioequivalence of
      the two formulations was determined on 12 normal healthy male volunteers in a
      single-dose, two-period, two-sequence, two-treatment crossover study. MFCA plasma
      concentrations were analyzed with this validated HPLC method. The normal pivotal
      parameters, AUC(0-last), AUC(0-inf) and Cmax, were calculated and compared using
      the SAS General Linear Model computer program. The two one-sided t distribution
      test was also performed, as well as the 90% confidence-interval method, for the
      mean difference of the three pivotal parameters. The results suggest that these
      two flavoxate tablet formulations are non-bioequivalent when orally administered
      in a 400-mg dose of two tablets. This result was consistent with the in vitro
      dissolution of these two formulations.

PMID- 11232857
TI  - Determination of terbutaline enantiomers in human urine by coupled achiral-chiral
      high-performance liquid chromatography with fluorescence detection.
AB  - A coupled achiral-chiral high-performance liquid chromatographic system with
      fluorescence detection at excitation/emission wavelengths of 276/306 nm has been
      developed for the determination of the enantiomers of terbutaline, (S)-(+)
      terbutaline and (R)-(-)-terbutaline in urine. Urine samples were prepared by
      solid-phase extraction with Sep-pak silica, followed by HPLC. The terbutaline was
      preseparated from the interfering components in urine on Phenomenex silica column
      and the terbutaline enantiomers and betaxolol were resolved and determined on a
      Sumichiral OA-4900 chiral stationary phase. The two columns were connected by a
      switching valve equipped with silica precolumn. The precolumn was used to
      concentrate the terbutaline in the eluent from the achiral column before back
      flushing onto the chiral phase. For each enantiomer the assay was linear between
      1 and 250 ng/ml (R2=0.9999) and the detection limit was 0.3 ng/ml. The intra-day
      variation was between 4.6 and 11.6% in relation to the measured concentration and
      the inter-day variation was 4.3-11.0%. It has been applied to the determination
      of (S)-(+)-terbutaline and (R)-(-)-terbutaline in urine from a healthy volunteer
      dosed with racemic terbutaline sulfate.

PMID- 11232859
TI  - Determination of urinary methylated purine pattern by high-performance liquid
      chromatography.
AB  - We describe the group selective separation and quantification of unmodified and
      modified purines in human urine by high-performance reverse phase liquid
      chromatography. The pattern of oxypurines and methylated purines: hypoxanthine
      (Hx), xanthine (X), 1-methyl hypoxanthine (1-MHx), 1-methyl guanine (1-MG), 3
      methyl guanine (3-MG), 7-methyl guanine (7-MG), 1-methyl xanthine (1-MX), 3
      methyl xanthine (3-MX), 7-methyl xanthine (7-MX), 1,7-dimethyl guanine (1,7-dMG),
      1,3-dimethyl xanthine (1,3-dMX), 1,7-dimethyl xanthine (3,7-dMX) and 1,3,7
      trimethyl xanthine (1,3,7-tMX) were determined in a single run in urine of a
      healthy subject and a gout patient before and after treatment with allopurinol.
      This method may be useful to investigate the urinary pattern of methylated bases
      in diseases involving purine metabolism.

PMID- 11232860
TI  - Stereospecific analysis of ecstasy-like N-ethyl-3,4-methylenedioxyamphetamine and
      its metabolites in humans.
AB  - A chiral HPLC method has been developed for the ecstasy analogue (R,S)-N-ethyl
      3,4-methylenedioxyamphetamine (MDE) and its metabolites o-glucuronyl-(R,S)-N
      ethyl-4-hydroxy-3-methoxyamphetamine (HME) and (R,S)-3,4
      methylenedioxyamphetamine (MDA) in human plasma. The chiral discrimination of the
      compounds was carried out with an enantioselective HPLC method using beta
      cyclodextrin in the mobile phase for MDE and MDA and a chiral protein phase
      (chiral-CBH) for HME. MDE and MDA were detected fluorimetrically at 322 nm, while
      the major metabolite HME was selectively determined by electrochemical detection
      at +600 mV. After hydrolysis of the conjugates using beta
      glucuronidase/arylsulfatase and solid-phase extraction with a cation-exchange
      phase for sample preparation high recovery rates of more than 95% were yielded.
      The limit of quantitation for the enantiomers of MDE and its metabolites in
      plasma were between 1.2 (MDA) and 16 ng/ml (HME) and the relative method standard
      deviations (V(xO), Table 1) were less than 3%. The methods described have been
      used successfully in the enantioselective quantitation of the compounds in plasma
      samples obtained from six healthy volunteers in a clinical study after oral
      administration of 140 mg racemic MDE hydrochloride. Significant differences were
      found in the plasma concentrations of the examined stereoisomers. Whereas the R
      enantiomer of the parent substance, MDE, was predominant in the plasma samples
      investigated, higher plasma concentrations of the S-enantiomers of the
      metabolites MDA and HME were measured.

PMID- 11232861
TI  - Screening of beta-2 agonists and confirmation of fenoterol, orciprenaline,
      reproterol and terbutaline with gas chromatography-mass spectrometry as
      tetrahydroisoquinoline derivatives.
AB  - A new method for a comprehensive screening and confirmation of beta-2 agonists in
      human urine is presented based on gas chromatography-low-resolution mass
      spectrometry (GC-MS) using electron impact ionisation (EI). After hydrolysis of
      the conjugates with beta-glucuronidase/arylsulfatase a derivatisation step with
      formaldehyde converts fenoterol, orciprenaline, reproterol and terbutaline to one
      derivative, a tetrahydroisoquinoline, while the other beta-2 agonists remain
      unchanged. Liquid-liquid extraction and trimethylsilylation follow. The
      tetrahydroisoquinoline derivatives show good gas chromatographic and mass
      spectrometric behaviour. The detection limit of these four beta-2 agonists in the
      screening using low-resolution mass spectrometry is 10 ng/ml of urine. The other
      beta-2 agonists are detected as parent compounds with the same recovery after
      sample preparation with and without formaldehyde. The EI mass spectra of the
      tetrahydroisoquinoline derivatives are presented.

PMID- 11232862
TI  - Translation termination in eukaryotes: from simplicity to complexity.
AB  - The last forty years of molecular biology and biochemistry were enormously rich
      in discoveries, which were not foreseen even by the most eminent scientists of
      that time. The findings of 1993-2000 profoundly enlarged our views on translation
      termination, clearly showing that our previous understanding was enormously
      oversimplified. Now the structural basis is created for much better insight into
      functions of termination factors. The story of translation termination in
      eukaryotes could be taken as an illustration of a general trend of molecular
      biology: "From simplicity to complexity". However, genuine knowledge requires
      that after this stage a third phase has to be reached, which is "From complexity
      to clarity". This has not yet been achieved in translation termination and
      therefore makes this topic quite attractive for researchers.

PMID- 11232863
TI  - Cytotoxic effects of colicins E1 and E3 on v-myb-transformed chicken monoblasts.
AB  - Colicins show a considerable cytostatic activity, which is much less known and
      understood than their killing activity targeting bacteria of the
      Enterobacteriaceae family. In this communication, the cytotoxic effects of
      colicins E1 and E3 on v-myb-transformed chicken monoblasts BM2 are presented. We
      detected clear reduction of the viable cell number induced by colicins E1 and E3,
      occurring without apparent changes in cell cycle profiles. The level of
      inhibition was proportional to the colicin concentration within the limits of 0.5
      1.25 microg/ml. This result documents that colicins produced by
      Enterobacteriaceae exert their cytotoxic effects on leukemic cells.

PMID- 11232864
TI  - A short note on micronucleoli in the course of terminal maturation of human
      erythroblasts.
AB  - The incidence of micronucleoli in the course of terminal differentiation of human
      erythroblasts was studied by the cytochemical procedures for demonstration of RNA
      and characteristic proteins of interphase AgNORs. The last dividing stages of the
      erythroid lineage--polychromatophylic erythroblasts--characterized by the
      presence of micronucleoli exhibited significantly larger values of the nucleolar
      coefficient in specimens stained for AgNOR proteins than in those stained for
      RNA. In addition, both these and terminal non-dividing nucleated stages of the
      erythroid lineage--orthochromatic erythroblasts--possessed micronucleoli after
      staining for RNA in a much smaller percentage of cells than after staining for
      AgNOR proteins. Thus, both these observations indicate that micronucleoli in the
      course of terminal maturation of erythroblasts apparently lose the nucleolar RNA
      detectable by the light microscopic cytochemistry. In addition, silver-stained
      micronucleoli--nucleolar remnants--were also noted in erythroblasts expelling the
      nucleus.

PMID- 11232865
TI  - Changes in immunocytochemical localization of cytoskeletal proteins in boar
      spermatozoa after acrosome reaction induced by specific cytoskeletal inhibitors.
AB  - Certain morphological changes such as rearrangement of cytoskeletal proteins of
      the mammalian spermatozoa are detectable during the AR. The type of changes
      differs according to the studied sperm species and follows the course of AR.
      Relocation of cytoskeletal structures was previously observed especially in the
      case of actin-, alpha-, gamma-tubulin- and spectrin-containing structures. To
      prove these findings we used specific inhibitors of cytoskeletal proteins (eg.
      colcemide, cytochalasine B, nocodazole and vinblastine). It has been shown that
      the AR is influenced by cytoskeletal inhibitors, but the obtained results also
      document that cytoskeletal proteins actin, tubulin and spectrin play a
      significant role in the course of AR in vitro. Our results of confocal and
      electron microscopy also demonstrate visible changes of actin-, tubulin- and
      spectrin-containing structures after the AR. Our data indicate that specific
      cytoskeletal inhibitors influence the AR and they prove the role of cytoskeletal
      proteins in this process.

PMID- 11232866
TI  - Analysis of sister-chromatid exchanges and micronuclei in cultured human
      lymphocytes treated with insulin.
AB  - Insulin is an anabolic hormone that may facilitate development of malignant
      diseases in various susceptible tissues due to stimulation of mitotic divisions.
      In this work, an evaluation of mitogenic and genotoxic effects of human
      recombinant insulin has been performed in cultures of human peripheral blood
      lymphocytes. Genotoxic effects were studied by the following test systems: (1) in
      vitro SCE test, and (2) cytokinesis-blocked micronucleus assay. The obtained
      results indicate that insulin stimulates mitotic division at an optimal
      concentration of 10(-8) M. On the other hand, insulin has not exhibited genotoxic
      properties under experimental conditions in this investigation.

PMID- 11232867
TI  - Transforming growth factor-beta1 induces junB mRNA accumulation, G1-phase arrest,
      and pRb dephosphorylation in human leukemia HL-60 cells.
AB  - Although TGF-beta1 unambiguously functions as a regulator of hematopoietic
      differentiation, its significance for the development of myeloid lineage is still
      questionable. In this study three components of early response to TGF-beta1
      treatment were investigated in human promyelocytic leukemia HL-60 cells. Changes
      in junB mRNA accumulation and pRb dephosphorylation were accompained by
      accumulation of cells in G1 phase of the cell cycle. Time dependence of these
      changes may implicate mutual cooperation of the pRb and junB in the cell cycle
      control. It can be concluded that, although myeloid HL-60 cells are known to
      require rather complex cytokine stimulation to fully differentiate, they clearly
      possess the ability to respond to TGF-beta1.

PMID- 11232868
TI  - Analysis of paternal alleles in nucleated red blood cells enriched from maternal
      blood.
AB  - The purpose of our study was to identify paternal alleles in NRBC enriched from
      maternal peripheral blood for detection of the presence of foetal cells in the
      maternal circulation and to establish a reliable non-invasive method which should
      allow following genetic testing. For enrichment of foetal cells from peripheral
      maternal blood we combined Ficoll-Paque density gradient centrifugation and MACS.
      Maternal leukocytes were firstly depleted using anti-CD14 and anti-CD45
      microbeads. NRBC were sorted from the CD14-/CD45- fraction by positive selection
      using CD71 microbeads. Paternal alleles in the CD14-/CD45-/CD71+ fraction were
      indicated by the PCR method using HLA (DRB1, DQB1, DQA1) and Polymarker System
      (LDLR, GYPA, HBGG, D7S8, GC) as genetic markers. Different paternal alleles of
      studied 8 loci were detected in 13 out of 19 samples of cells enriched from
      maternal peripheral blood between the 13th and 36th week of gestation. Our
      results demonstrate that foetal cells enriched from maternal peripheral blood may
      be used as a source of foetal DNA for prenatal diagnosis, paternity testing and
      other application.

PMID- 11232869
TI  - Effects of tamoxifen and melatonin on mammary gland cancer induced by N-methyl-N
      nitrosourea and by 7,12-dimethylbenz(a)anthracene, respectively, in female
      Sprague-Dawley rats.
AB  - Chemopreventive effects were analysed of antioestrogen TAM and of MEL on NMU- or
      DMBA-induced mammary gland cancer, respectively, in female Sprague-Dawley rats.
      NMU was administered intraperitoneally in two doses each of 50 mg/kg b.w. between
      46th-57th postnatal days. DMBA was given by gavage in one dose (20 mg per animal)
      between 50th-54th postnatal days. The treatment with MEL began 12 days and the
      treatment with TAM 10 days before carcinogen administration; both chemopreventive
      substances were administered until the end of the experiment (24 weeks after
      carcinogen application). TAM was administered subcutaneously twice a week in a
      dose 2.5 mg/kg b.w. MEL was given in tap water (20 mg/ml) daily between 3 p.m. to
      8 a. m. The tumour incidence, tumour frequency per group and animal, latency
      period, tumour volume, body weight gain in the rats and weight of uterus (in the
      experiment with NMU) were evaluated. TAM suppressed carcinogenesis to 0%
      incidence like TAM+MEL in both the NMU and DMBA models. In NMU-induced mammary
      carcinogenesis MEL lowered the tumour volume (although statistically non
      significantly) by 30% in comparison with the control group; in DMBA-induced
      mammary carcinogenesis it lowered the tumour volume (2.70 +/- 0.81 cm3 vs. 0.90
      +/- 0.33 cm3) and lengthened (non-significantly) the latency period (by 12 days).
      The weight gain of animals in both NMU and DMBA models and relative uterus weight
      in the NMU model were significantly lower in the groups treated with TAM and
      TAM+MEL as compared to the control group and the group treated with MEL.
      Evaluation of the combined effect of TAM+MEL was not possible due to total
      suppression of carcinogenesis by TAM. TAM and TAM+MEL are highly effective agents
      in rat mammary carcinogenesis prevention, but the side effects of TAM in humans
      limits its use in clinical oncology.

PMID- 11232870
TI  - Effectiveness of hand-cleansing agents for removing methicillin-resistant
      Staphylococcus aureus from contaminated hands.
AB  - OBJECTIVE: The effectiveness of hand-cleansing agents in removing a hospital
      strain of methicillin-resistant Staphylococcus aureus from artificially
      contaminated hands of five volunteers was studied. DESIGN: The products used were
      plain liquid soap, ethyl alcohol 70% (by weight), 10% povidone-iodine liquid soap
      (PVP-I), and chlorhexidine gluconate (4%) detergent. The experiments were
      performed using a Latin square statistical design, with two 5x4 randomized
      blocks. The removal rates of S aureus cells from contaminated fingertips were
      estimated by analysis of variance, the response variable being the log10
      reduction factor (RF), ie, log10 of the initial counts minus log10 of the final
      counts. In the first and second blocks, the fingertips of the volunteers were
      contaminated in mean with 3.76 log10 colony-forming units ([CFU] light
      contamination hand) and 6.82 log10 CFU (heavy-contamination hand), respectively.
      RESULTS: In the first block, there were significant differences between
      treatments (P<.05). The 10% PVP-I (RF, 3.76) and 70% ethyl alcohol (RF, 3.51) had
      significantly higher removal rates than plain liquid soap (RF, 1.96) and 4%
      chlorhexidine (RF, 1.91). In the second block, 10% PVP-I (RF, 4.39) and 70% ethyl
      alcohol (RF, 3.27) also were significantly more effective than plain liquid soap
      (RF, 1.77) and 4% chlorhexidine (RF, 1.37; P<.05). Plain liquid soap was
      significantly more effective than chlorhexidine (4%) detergent. CONCLUSIONS: The
      results suggest that 10% PVP-I and 70% ethyl alcohol may be the most effective
      hand-cleansing agents for removing methicillin-resistant S aureus strain from
      either lightly or heavily contaminated hands.

PMID- 11232872
TI  - New-onset rhinitis symptoms among hospitalized patients: are flowers a culprit?
AB  - New-onset rhinitis symptoms following admission to the hospital were reported by
      12.7% of surveyed patients. Presence of flower arrangements in the proximity of
      patients' beds was highly associated with the development of new rhinitis (odds
      ratio, 9.7; 95% confidence interval, 4.3-21.7), or what may be more aptly
      referred to as "florocomial" rhinitis.

PMID- 11232871
TI  - Multidrug-resistant bacteria infection control: study of compliance with
      isolation precautions in a Paris university hospital.
AB  - Isolation practices in a university hospital were analyzed for 137 patients with
      multidrug-resistant bacteria. Isolation was ordered in writing by physicians for
      40% and instituted by nurses for 60%; 74% were isolated. Compliance depended on
      physician ordering in writing (odds ratio, 36.3; 95% confidence interval, 4.8
      274.9). Nurses complied best with hand washing.

PMID- 11232873
TI  - Hepatitis B prevention strategies among pediatric hemodialysis centers.
AB  - We surveyed pediatric hemodialysis centers (PHDCs) concerning their hepatitis B
      virus (HBV) prevention strategies. One hundred thirty-one patients were being
      dialyzed in these PHDCs in December 1996. Although all centers immunized HBV
      susceptible hemodialysis patients and had infection control policies to curtail
      the spread of HBV infection, most centers were not in compliance with all of the
      Centers for Disease Control and Prevention recommendations for isolating
      hepatitis B surface antigen-positive patients.

PMID- 11232874
TI  - Reality check: should we try to detect and isolate vancomycin-resistant
      enterococci patients?
AB  - Antimicrobial resistance, including vancomycin resistance in enterococci (VRE),
      is a growing problem in healthcare facilities. This "Reality Check" session
      focused on the question of whether we should try to detect and isolate patients
      colonized or infected with VRE.

PMID- 11232875
TI  - Development of minimum criteria for the initiation of antibiotics in residents of
      long-term-care facilities: results of a consensus conference.
AB  - Establishing a clinical diagnosis of infection in residents of long-term-care
      facilities (LTCFs) is difficult. As a result, deciding when to initiate
      antibiotics can be particularly challenging. This article describes the
      establishment of minimum criteria for the initiation of antibiotics in residents
      of LTCFs. Experts in this area were invited to participate in a consensus
      conference. Using a modified delphi approach, a questionnaire and selected
      relevant articles were sent to participants who were asked to rank individual
      signs and symptoms with respect to their relative importance. Using the results
      of the weighting by participants, a modification of the nominal group process was
      used to achieve consensus. Criteria for initiating antibiotics for skin and soft
      tissue infections, respiratory infections, urinary infections, and fever where
      the focus of infection is unknown were developed.

PMID- 11232877
TI  - Psychiatric inpatients at risk for HIV, TB, and hepatitis.

PMID- 11232879
TI  - Colonization with multiresistant bacteria and quality of life in residents of
      long-term-care facilities.

PMID- 11232878
TI  - Radiographic films: potential source of nosocomial infections?

PMID- 11232880
TI  - Infection control in Africa south of the Sahara.

PMID- 11232881
TI  - Raising the bar: the need for standardizing the use of "standard precautions" as
      a primary intervention to prevent occupational exposures to bloodborne pathogens.

PMID- 11232882
TI  - Hospital bloodborne pathogens programs: program characteristics and blood and
      body fluid exposure rates.
AB  - OBJECTIVE: To describe hospital practices and policies relating to bloodborne
      pathogens and current rates of occupational exposure among healthcare workers.
      PARTICIPANTS AND METHODS: Hospitals in Iowa and Virginia were surveyed in 1996
      and 1997 about Standard Precautions training programs and compliance. The primary
      outcome measures were rates of percutaneous injuries and mucocutaneous exposures.
      RESULTS: 153 (64%) of 240 hospitals responded. New employee training was offered
      no more than twice per year by nearly one third. Most (79%-80%) facilities
      monitored compliance of nurses, housekeepers, and laboratory technicians;
      physicians rarely were trained or monitored. Implementation of needlestick
      prevention devices was the most common action taken to decrease sharps injuries.
      Over one half of hospitals used needleless intravenous systems; larger hospitals
      used these significantly more often. Protected devices for phlebotomy or
      intravenous placement were purchased by only one third. Most (89% of large and
      80% of small) hospitals met the recommended infection control personnel-to-bed
      ratio of 1:250. Eleven percent did not have access to postexposure care during
      all working hours. Percutaneous injury surveillance relied on incident reports
      (99% of facilities) and employee health records (61%). The annual reported
      percutaneous injury incidence rate from 106 hospitals was 5.3 injuries per 100
      personnel. Compared to single tertiary-referral institution rates determined more
      than 5 years previously, current injury rates remain elevated in community
      hospitals. CONCLUSIONS: Healthcare institutions need to commit sufficient
      resources to Standard Precautions training and monitoring and to infection
      control programs to meet the needs of all workers, including physicians.
      Healthcare workers clearly remain at risk for injury. Further effective
      interventions are needed for employee training, improving adherence, and
      providing needlestick prevention devices.

PMID- 11232883
TI  - Impact of nosocomial infection on length of stay and functional improvement among
      patients admitted to an acute rehabilitation unit.
AB  - OBJECTIVE: To identify factors predictive of length of stay (LOS) and the level
      of functional improvement achieved among patients admitted to an acute
      rehabilitation unit for the first time, with special reference to the role of
      nosocomial infection. SETTING: A 40-bed acute rehabilitation unit within a 300
      bed, tertiary-care, public, university-affiliated hospital. STUDY POPULATION: All
      patients admitted to the unit between January 1997 and July 1998. DESIGN:
      Prospective cohort study in which demographic and clinical data, including
      occurrence of nosocomial infection, were collected during the entire unit
      admission of each patient. Multivariate linear regression analysis was used to
      identify factors predictive of unit LOS or improvement in functional status as
      measured by the change in the Functional Independence Measure (FIM) score between
      admission and discharge (deltaFIM). RESULTS: There were 423 admissions to the
      rehabilitation unit during the study period, of which 91 (21.5%) had spinal cord
      injury (SCI) as a principal diagnosis. One hundred seven nosocomial infections
      occurred during 84 (19.9%) of the 423 admissions. The most common infections were
      urinary tract (31.8% of all infections), surgical-site (18.5%), and Clostridium
      difficile diarrhea (15%). Only one patient died of infection. After controlling
      for severity of illness on admission, functional status on admission, age, and
      other clinical factors, the significant positive predictors of unit LOS were as
      follows: SCI (P<.001), pressure ulcer (.002), and nosocomial infection (<.001).
      Significant negative predictors of deltaFIM were age (P<.001), FIM score on
      admission (<.001), prior hospital LOS (.002), and nosocomial infection (.007).
      CONCLUSIONS: Several variables were identified as contributing to a longer LOS or
      to a smaller improvement in functional status among patients admitted for the
      first time to an acute rehabilitation unit. Of these variables, only nosocomial
      infection has the potential for modification. Studies of new approaches to
      prevent infections among patients undergoing acute rehabilitation should be
      pursued.

PMID- 11232884
TI  - Factors associated with tuberculin reactivity in two general hospitals in Mexico.
AB  - OBJECTIVE: To identify risk factors associated with tuberculin reactivity in
      healthcare workers (HCWs). DESIGN: Cross-sectional survey of tuberculin
      reactivity (2 TU of purified protein derivative (PPD) RT23, using the Mantoux two
      step test). SETTING: Two general hospitals located in a region with a high
      prevalence of tuberculosis and high bacille Calmette-Guerin (BCG) coverage.
      PARTICIPANTS: Volunteer sample of HCWs. RESULTS: 605 HCWs were recruited: 71.2%
      female; mean age, 36.4 (standard deviation [SD], 8.2) years; 48.9% nurses, 10.4%
      physicians, 26.8% administrative personnel; mean time of employment, 10.9 (SD,
      6.7) years. PPD reactivity (> or =10 mm) was found in 390 (64.5%). Multivariate
      analysis revealed an association of tuberculin reactivity with occupational
      exposure in the hospital: participation in autopsies (odds ratio [OR], 9.3; 95%
      confidence interval [CI95], 2.1-40.5; P=.003.), more than 1 year of employment
      (OR, 2.4; CI95, 1.1-5.0; P=.02), work in the emergency or radiology departments
      (OR, 2.0; CI95, 1.03-3.81; P=.04), being physicians or nurses (OR, 1.5; CI95,
      1.04-2.11; P=.03), age (OR, 1.04; CI95, 1.02-1.07 per year of age; P<.001), and
      BCG scar (OR, 2.1; CI95, 1.2-3.4; P=.005). CONCLUSIONS: Although the studied
      population has a high baseline prevalence of tuberculosis infection and high
      coverage of BCG vaccination, nosocomial risk factors associated with PPD
      reactivity were identified as professional risks; strict early preventive
      measures must be implemented accordingly.

PMID- 11232885
TI  - Bacteriological validation of a new apparatus for disinfection of hospital waste
      at the point of disposal.
AB  - OBJECTIVES: To evaluate the ability of a new apparatus (Dipsys 25, Societe SGN,
      Bagnols sur Ceze, France) to disinfect biomedical waste, including both
      potentially infectious agents and the normal saprophytic flora of the waste.
      METHODS: Disinfection was assessed using standard methods (reference strains were
      fixed on reference carriers according to the French AFNOR methods) and
      nonstandard assays. Assays in conditions of hospital use, evaluations of
      bacterial survival during storage, sporicidal effect, and spore survival during
      storage were performed in parallel. Finally, bactericidal effect in extreme
      conditions (association of high contamination and high bacterial protection
      conditions) was tested with normal fecal flora. Bacterial counts were performed
      after treatment by the apparatus and without treatment (controls). All tests were
      carried out in triplicate. RESULTS: In all treated carriers, a bacterial
      population decrease of at least 5 log10 was obtained. Assays performed in
      hospital-use conditions did not show any bacterial growth. Concerning the
      evaluation of sporicidal effect and spore revival during conservation, a minimum
      reduction of 5 log10 was observed in all assays performed, without survival.
      Finally, concerning assays in extreme conditions, the decrease of bacterial
      population was between 5 log10 and 10 log10 for vegetative anaerobes of normal
      fecal flora. CONCLUSION: Under our study conditions, the study apparatus reduced
      the tested microbial populations by a minimal factor of 5 log10. The main
      advantage of the apparatus is the opportunity to treat contaminated waste inside
      hospital wards, at the point of initial collection, without pulverization, by
      nonspecialized staff.

PMID- 11232887
TI  - World Health Day, 7 April 2001.

PMID- 11232886
TI  - The economic impact of methicillin-resistant Staphylococcus aureus in Canadian
      hospitals.
AB  - OBJECTIVES: To determine the costs associated with the management of hospitalized
      patients with methicillin-resistant Staphylococcus aureus (MRSA), and to estimate
      the economic burden associated with MRSA in Canadian hospitals. DESIGN: Patient
      specific costs were used to determine the attributable cost of MRSA associated
      with excess hospitalization and concurrent treatment. Excess hospitalization for
      infected patients was identified using the Appropriateness Evaluation Protocol, a
      criterion-based chart review process to determine the need for each day of
      hospitalization. Concurrent treatment costs were identified through chart review
      for days in isolation, antimicrobial therapy, and MRSA screening tests. The
      economic burden to Canadian hospitals was estimated based on 3,167,521 hospital
      discharges for 1996 and 1997 and an incidence of 4.12 MRSA cases per 1,000
      admissions. SETTING: A tertiary-care, university-affiliated teaching hospital in
      Toronto, Ontario, Canada. PATIENTS: Inpatients with at least one culture yielding
      MRSA between April 1996 and March 1998. RESULTS: A total of 20 patients with MRSA
      infections and 79 colonized patients (with 94 admissions) were identified. This
      represented a rate of 2.9 MRSA cases per 1,000 admissions. The mean number of
      additional hospital days attributable to MRSA infection was 14, with 11
      admissions having at least 1 attributable day. The total attributable cost to
      treat MRSA infections was $287,200, or $14,360 per patient The cost for isolation
      and management of colonized patients was $128,095, or $1,363 per admission. Costs
      for MRSA screening in the hospital were $109,813. Assuming an infection rate of
      10% to 20%, we determined the costs associated with MRSA in Canadian hospitals to
      be $42 million to $59 million annually. CONCLUSIONS: These results indicate that
      there is a substantial economic burden associated with MRSA in Canadian
      hospitals. These costs will continue to rise if the incidence of MRSA increases
      further.

PMID- 11232888
TI  - Efficacy of salpingography and transcervical recanalization in diagnosis,
      categorization, and treatment of fallopian tube obstruction.
AB  - PURPOSE: The efficacy of selective salpingography (SS) and transcervical
      recanalization (TCR) in diagnosis, categorization, and determination of optimal
      treatment modality for fallopian tube obstruction was investigated. METHODS: SS
      and, in some patients, TCR was performed in 430 patients with a diagnosis of
      obstruction of one or both fallopian tubes, as determined by hysterosalpingograms
      (HSG). All patients (age 21-46 years) had an infertility problem for at least 18
      months. RESULTS: In 196 patients, 325 tubes were patent on SS. TCR recanalized
      243 tubes in 176 patients. Disease of the distal tube was demonstrated in 66
      patients. There were 39 live babies in a group of 176 patients with successful
      TCR. Best live birth rate was in 7 of 12 (58%) patients with underlying
      endometriosis, followed by postsurgical strictures in inflammatory disease, 6 of
      31 (19%), and salpingitis isthmica nodosa in 25 of 168 (15%). There were no
      pregnancies in patients with cobblestone pattern of the distal tubes.
      CONCLUSIONS: SS and TCR were capable of correcting obstruction of the proximal
      tubes in 243 of 465 tubes in 176 of 234 patients (75%). With patency of the
      proximal tube restored, the distal tube could be assessed for changes indicative
      of damage to the ciliated epithelium which was likely to reduce the ability to
      become pregnant. This allowed for the triage of patients into groups benefiting
      from the relatively inexpensive and low complication TCR or patients in need of
      in vitro fertilization or similar assisted reproductive technologies.

PMID- 11232889
TI  - Feasibility of C-arm-supported CT fluoroscopy in percutaneous abscess drainage
      procedures.
AB  - PURPOSE: Evaluation of C-arm-supported CT fluoroscopy to facilitate percutaneous
      abscess drainage procedures. METHODS: Prospectively, 40 percutaneous drainage
      procedures were performed either with C-arm-supported CT fluoroscopy or with CT
      fluoroscopy alone. Hybrid imaging was performed on the CT couch after
      complementing a CT fluoroscopy scanner with a C-arm fluoroscopy unit. Procedure
      times, drainage revisions during follow-up, and postinterventional drainage
      periods were analyzed. RESULTS: When compared with exclusive CT fluoroscopic
      guidance, a median procedure time of 9 +/- 3.7 min versus 14.8 +/- 7.3 min was
      required for C-arm-supported CT fluoroscopy (p < 0.005, t-test). During follow
      up, eight drainage catheters had to be revised within the exclusive CT
      fluoroscopy group, while only two revisions were necessary within the C-arm
      supported CT fluoroscopy group. With C-arm-supported CT fluoroscopy,
      postinterventional drainage periods were reduced (median 13 vs 19 days; p <
      0.001, t-test). CONCLUSION: Compared with exclusive cross-sectional image
      guidance, C-arm-supported CT fluoroscopy seems to improve placement of abscess
      drainage catheters to possibly reduce procedure times, drainage catheter
      revisions, and postinterventional drainage periods.

PMID- 11232890
TI  - Percutaneous cholangioscopy in the management of biliary disease: experience in
      25 patients.
AB  - PURPOSE: To present our experience performing percutaneous cholangioscopy in the
      management of 25 patients with biliary disease. METHODS: During the last 3 years,
      26 percutaneous cholangioscopies were performed in 25 patients with common bile
      duct disease (n = 16), intrahepatic ducts disease (n = 6), and gallbladder
      disease (n = 4). Our patient population group included seven with common bile
      duct stones, three with intrahepatic lithiasis, and eight with benign strictures
      (six iatrogenic and two postinflammatory). In four patients malignancy was to be
      excluded, in two the tumor extent was to be evaluated, whereas in one case the
      correct placement of a metallic stent needed to be controlled. A 9.9 Fr flexible
      endoscope URF-P (Olympus, 1.2 mm working channel, 70-cm length) was used.
      RESULTS: In total, percutaneous cholangioscopy answered 30 diagnostic questions,
      was technically helpful in 19 cases (performing lithotripsy or biopsy or guiding
      a wire), and of therapeutic help in 12 (performing stone retrieval). In 24 of 26
      cases the therapeutic decision and the patient management changed because of the
      findings or because of the help of the method. In two cases biliary intervention
      failed to treat the cause of the disease. No major complication due to the use of
      the endoscopy was noted. CONCLUSIONS: Percutaneous cholangioscopy is a very
      useful tool in the management of patients with biliary disease. The method can
      help in diagnosis, in performing complex interventional procedures, and in making
      or changing therapeutic decisions.

PMID- 11232891
TI  - Percutaneous ablation of peripheral pseudoaneurysms using thrombin: a simple and
      effective solution.
AB  - PURPOSE: To assess the effectiveness of tissue adhesive and thrombin solution in
      the percutaneous ablation of peripheral artery pseudoaneurysms. METHODS: Twenty
      five pseudoaneurysms were treated over a 33-month period; all had failed
      ultrasound-guided compression. Tissue adhesive or thrombin solution was injected
      percutaneously, with needle tip position and changes within the aneurysm
      confirmed with color Doppler ultrasound. In 19 cases we utilized a protective
      balloon inflated across the aneurysm neck prior to the injection of tissue
      adhesive and in six cases used thrombin injection alone. Seven patients were
      anticoagulated. Patients were followed up after the procedure. RESULTS: All 25
      aneurysms were treated successfully; two patients required a return visit and
      there were no immediate complications or peripheral emboli detected. One patient
      developed a contralateral pseudoaneurysm. CONCLUSIONS: The percutaneous injection
      of pseudoaneurysms is a safe, atraumatic, and effective treatment for femoral
      artery pseudoaneurysms in the peripheral circulation. There are significant
      advantages over ultrasound-guided compression or surgical repair.

PMID- 11232892
TI  - Improvement in claudication after angioplasty of distal ostial collateral
      stenosis in patients with long-segment occlusion of the femoral artery.
AB  - PURPOSE: To evaluate the angiographic and clinical effects of percutaneous
      transluminal angioplasty (PTA) of distal ostial collateral stenoses in patients
      with claudication and long-segment occlusion of the superficial femoral artery
      (SFA). METHODS: In ten patients (9 men, 1 woman) with stable intermittent
      claudication due to chronic long-segment occlusion of the SFA a high-grade
      stenosis of the distal collateral ostium of the deep femoral artery to the
      popliteal artery were dilated. PTA was performed using popliteal artery access.
      Claudication distances on the treadmill and ankle-brachial pressure indices (ABI)
      at rest were analyzed before, 1 week, and 14 weeks after PTA. RESULTS: Initial
      technical success was obtained in all patients. There were no significant
      periprocedural local complications. The initial mean claudication distance on the
      treadmill increased significantly from 107 +/- 65 m to 306 +/- 209 m (p < 0.01),
      the maximal claudication distance from 203 +/- 128 m to 392 +/- 167 m (p < 0.01).
      The mean ABI changed slightly but significantly (0.61 +/- 0.08 vs. 0.64 +/- 0.07;
      p < 0.05). Early follow-up after 14 weeks revealed no clinical deterioration.
      CONCLUSION: This new technique is considered helpful in patients with well
      defined claudication and long-segment occlusion of the SFA.

PMID- 11232894
TI  - Endovascular embolization of varicoceles: resorption of tungsten coils in the
      spermatic vein.
AB  - PURPOSE: To investigate whether resorption of tungsten coils occurs in patients
      with varicoceles treated by endovascular embolization of the spermatic vein.
      METHODS: Patients who had previously had varicocele embolization were requested
      by letter to attend the radiology department. Blood levels of tungsten were
      compared with a group of controls. Fluoroscopic images of the coils were taken
      and compared with those obtained during the original procedures. RESULTS:
      Nineteen patients attended, whose procedure had been done 19-57 months previously
      (mean 40 months). Blood levels of tungsten were raised in 18 patients compared
      with the controls. Radiographic evidence of loss of substance of the coils was
      seen in four patients. CONCLUSION: Tungsten coil resorption occurs in varicocele
      embolization. In view of the unknown long-term effects of raised blood tungsten
      levels and the availability of alternative embolization agents, we feel that it
      is unwise to persist in the use of tungsten coils in this application.

PMID- 11232893
TI  - The timing and frequency of complications after peripheral percutaneous
      transluminal angioplasty and iliac stenting: is a change from inpatient to
      outpatient therapy feasible?
AB  - PURPOSE: A prospective study was performed to assess the frequency and timing of
      complications after transluminal angioplasty and stent placement with a view to
      changing our practice and performing these procedures on an outpatient basis.
      METHOD: A total of 266 angioplasties and 51 stent deployments were attempted on
      240 consecutive patients. Immediate complications were documented by the
      radiologists. The timing and nature of any complications during and beyond the
      first 24 hr were reported by the vascular surgeons. RESULTS: There were 14
      complications in 240 patients, giving a complication rate of 4.8% per vessel
      segment dilated. There were five major and nine minor complications. Eighty-six
      percent of complications were evident before the patient had left the angiography
      suite. All complications were evident within 4.5 hr of the procedure. CONCLUSION:
      The timing of complications suggests it would be reasonable to perform
      percutaneous transluminal angioplasties and iliac stenting on an outpatient basis
      in suitable patients.

PMID- 11232895
TI  - In vivo evaluation of vena caval filters: can function be linked to design
      characteristics?
AB  - PURPOSE: To compare the five vena caval filters marketed in the United States and
      one investigational vena caval filter and to determine whether there is an
      association between their design and their in vivo function. METHODS: Four of
      each type of filter--Simon Nitinol (SN), Bird's Nest (BN), Vena Tech (VT),
      Greenfield stainless steel (PSGF), Greenfield titanium (TGF), and the
      investigational stent cone filter (NGF)--were studied for 60 days in 12 sheep.
      Radiographic and pathologic outcomes to be assessed included clot capture and
      resolution, vena caval penetration, position of the filter, thrombogenicity, and
      vessel wall reaction. RESULTS: Filters differed with respect to the number of
      clot-trapping levels and the interdependence of the legs. All devices were
      successfully placed. Intentionally embolized clot was captured. One VT and two SN
      filters migrated in response to clot capture. Resolution of thrombus was
      variable, and related to the design of the device. Fibrin webbing was widely
      present with the VT, BN, and SN filters but limited in the others. The VT and NGF
      filters demonstrated the most stable filter base diameter. CONCLUSIONS: The
      performance of vena caval filters differs with respect to clot resolution and
      mechanical stability. Interdependent filter limbs and single-stage conical
      capture sites appear to result in more favorable performance in in vivo studies.

PMID- 11232896
TI  - Protective effects of repetitive injections of radiographic contrast media on the
      subsequent tolerance to ischemia in the isolated rat heart.
AB  - PURPOSE: Despite detailed knowledge of the effects of X-ray contrast media on
      cardiac function, no studies have examined the effect of contrast media
      injections on the subsequent tolerance to ischemia in the heart. METHODS:
      Isolated perfused rat hearts were exposed to repetitive injections of iohexol,
      iodixanol, or ioxaglate before 30 min of global ischemia and 120 min of
      reperfusion. These groups were compared with control (no pretreatment) and
      ischemic preconditioning known to reduce infarct size. Physiologic variables and
      infarct size were measured RESULTS: Pretreatment with iodixanol reduced infarct
      size significantly compared with control and thus afforded protection against
      ischemia. Injections with iohexol and ioxaglate reduced infarct size, although
      not significantly, compared with control. CONCLUSION: Pretreatment of the
      isolated rat heart with commonly used contrast media enhances the cardiac
      tolerance to subsequent ischemia. The mechanism behind this protective effect
      could not be determined, but could involve stretching of the heart and/or
      generation of nitric oxide.

PMID- 11232897
TI  - Pseudoaneurysm of the common hepatic artery: treatment with a stent-graft.
AB  - We report a case of a pseudoaneurysm of the common hepatic artery treated with a
      stent-graft in a 67-year-old man. The patient presented with severe catheter
      bleeding through a drain following surgical and interventional procedures
      performed for therapeutic management of a choledochal cholangiocarcinoma.
      Selective hepatic arteriography showed a pseudoaneurysm close to the origin of
      the gastroduodenal artery. After a preliminary attempt at arterial embolization,
      it was decided to use a stent-graft to bridge the false aneurysm. Complete
      pseudoaneurysm exclusion was seen after the procedure with preservation of
      hepatic arterial flow.

PMID- 11232898
TI  - Percutaneous endovascular stent-graft for iliac pseudoaneurysm following lumbar
      discectomy.
AB  - In a 24-year-old woman, an iliac pseudoaneurysm following lumbar discectomy was
      successfully treated by percutaneous placement of a self-expanding stent-graft. A
      postprocedural angiogram demonstrated complete exclusion of the pseudoaneurysm
      without leakage of contrast agent.

PMID- 11232900
TI  - Treatment of a recurrent choanal atresia by balloon dilatation.
AB  - A 16-year-old female patient with recurrent stenosis after unilateral choanal
      atresia that had been treated by surgery and laser therapy presented with
      restenosis 3 weeks after laser resection. As an alternative to repeat surgery,
      she was treated by balloon dilatation. Four balloon dilatations were performed
      (three at 4-week intervals and the last after an 8-week interval) over a 4-month
      period on an outpatient basis. She tolerated the treatment well without any
      complications. Over a follow-up period of 2 years the choana has remained
      completely open. The balloon dilatation described in this context here for the
      first time may be a good alternative to repeated operations in the treatment of
      recurrent choanal atresia, with minimal stress to the patient.

PMID- 11232899
TI  - Coil embolization treatment in pulmonary artery branch rupture during Swan-Ganz
      catheterization.
AB  - Rupture of the pulmonary artery or one of its branches during Swan-Ganz
      catheterization is a complication that is rare but remains fatal in almost 50% of
      cases. The risk factors and mechanisms involved in the pathogenesis of this
      accident have been widely reported. Management is twofold: resuscitation
      procedures and specific medical or even surgical treatment. We report a case of
      pulmonary artery rupture occurring during Swan-Ganz catheterization that was
      treated by coil embolization. This technique, which is quick and simple to use,
      would appear to be very promising. This is the first case of successful emergency
      treatment of pulmonary artery rupture using an endovascular technique.

PMID- 11232901
TI  - Pneumoperitoneum caused by transhepatic air leak after metallic biliary stent
      placement.
AB  - A self-expanding metallic biliary stent was placed for palliation of a common
      bile duct obstruction in a 68-year-old male with unresectable pancreatic head
      cancer 3 days after initial percutaneous right transhepatic catheter
      decompression. The stent crossed the ampulla of Vater. Three days later, the
      stent was balloon-dilated and the percutaneous access was removed. At removal, a
      small contrast leak from the transhepatic tract was seen. Three days later,
      pneumoperitoneum was found with symptoms of peritoneal irritation and fever. A
      widely open sphincter of Oddi caused by the metallic stent, accompanied by
      delayed sealing of the transhepatic tract, may have caused the air and bile
      leakage into the peritoneal space. This case shows that pneumoperitoneum may
      occur without ductal tear or bowel injury, with a biliary stent crossing the
      ampulla of Vater.

PMID- 11232902
TI  - Carbon dioxide and gadopentetate dimeglumine venography to guide percutaneous
      vertebroplasty.
AB  - Percutaneous vertebroplasty with polymethylmethacrylate (PMMA) is an effective
      procedure for relieving pain due to vertebral body compression fractures. The
      technique employs iodinated contrast venography to exclude needle placement
      directly within the basivertebral complex. We present two cases in which carbon
      dioxide (CO2) and gadopentetate dimeglumine venography was used to guide
      percutaneous vertebroplasty in patients with a contraindication to iodinated
      contrast.

PMID- 11232903
TI  - Treatment of post-stent gastroesophageal reflux by anti-reflux Z-stent.
AB  - Severe symptoms of heartburn and retrosternal pain consistent with gastro
      esophageal reflux (GER) developed in a patient following placement of a
      conventional self-expanding 16-24-mm-diameter x 12-cm-long esophageal stent
      across the gastroesophageal junction to treat an obstructing esophageal
      carcinoma. A second 18-mm-diameter x 10-cm-long esophageal stent with anti-reflux
      valve was deployed coaxially and reduced symptomatic GER immediately. Improvement
      was sustained at 4-month follow-up. An anti-reflux stent can be successfully used
      to treat significant symptomatic GER after conventional stenting.

PMID- 11232904
TI  - Re: Assessment of reintervention with tracheobronchial metallic stenting for
      malignant airway stenoses.

PMID- 11232905
TI  - Re: Transjugular intrahepatic portosystemic shunt for intractable esophageal
      gastric variceal hemorrhage in a patient with idiopathic myelofibrosis.

PMID- 11232906
TI  - Re: Peripheral venous access ports: outcomes analysis in 109 patients.

PMID- 11232907
TI  - A cognitive model of the positive symptoms of psychosis.

PMID- 11232908
TI  - Language in schizophrenia and its relationship to formal thought disorder.
AB  - BACKGROUND: Although poor language test performance has been documented in
      schizophrenia, its relationship to formal thought disorder remains unclear.
      METHOD: Forty schizophrenic patients were administered eight language tests and,
      under blind conditions, rated for formal thought disorder. Measures of general
      intellectual function were also obtained. RESULTS: Performance on all language
      tests was significantly correlated with the general intellectual measures. Three
      language test scores also showed significant correlations with formal thought
      disorder scores. Multiple regression and analysis of intellectually preserved
      patients suggested particular associations of formal thought disorder with
      semantic comprehension and picture description. CONCLUSIONS: General intellectual
      impairment is an important determinant of poor language test performance in
      schizophrenia, but presence of formal thought disorder may also contribute. A
      higher-order semantic deficit may be particularly relevant to both linguistic
      impairment and formal thought disorder.

PMID- 11232909
TI  - Theory of mind impairments in schizophrenia: symptomatology, severity and
      specificity.
AB  - BACKGROUND: Several studies have examined the ability of schizophrenic patients
      to represent mental states ('theory of mind': ToM). There is consensus that some
      patients have impaired ToM, but there is disagreement about the relation between
      ToM and symptomatology, and about the severity and specificity of the deficit.
      METHODS: Two first-order and one second-order false belief tests of ToM were
      given to groups of schizophrenic patients and psychiatric and normal controls.
      The relation between ToM and symptomatology was explored using regression and
      symptom subgroup analyses. Severity was investigated by using the same task
      methodology as in autism research, to enable direct comparison with that
      disorder. Specificity was investigated using matched control tasks which were as
      difficult as the ToM tasks, but did not require ToM. RESULTS: Symptom subgroup
      analysis showed that schizophrenic patients with behavioural signs were impaired
      relative to controls on ToM, and that remitted patients and a single case with
      passivity symptoms performed as well as controls. Regression analysis showed that
      ratings of behavioural signs predicted impaired ToM in schizophrenia. There was
      weak evidence that a subgroup with paranoid symptoms had ToM impairments,
      although these were associated with low IQ. Schizophrenic patients only showed
      ToM deficits on the second-order task. No impairments appeared on the matched
      control tasks which did not require ToM. CONCLUSIONS: There is a clear
      association between ToM impairment and behavioural signs in schizophrenia.
      Deficits in paranoid patients are harder to detect with current tasks and may be
      compensated for by IQ-dependent problem-solving skills. ToM impairments in
      schizophrenia are less severe than in autism, but are specific and not a
      reflection of general cognitive deficits.

PMID- 11232910
TI  - 'Hyper-priming' in thought-disordered schizophrenic patients.
AB  - BACKGROUND: A number of studies have suggested that indirect semantic priming is
      enhanced in thought-disordered schizophrenics. However, research on direct
      semantic priming has produced conflicting results. The aim of the present study
      was to resolve some of the ambiguities of previous findings. METHODS: For the
      present study, 44 schizophrenic patients were split according to the presence of
      associative loosening into a positive thought-disordered (TD) and non-positive
      thought-disordered (NTD) group. Thirty healthy subjects and 36 psychiatric
      patients served as controls. RESULTS: Schizophrenics displayed increased indirect
      semantic priming compared with psychiatric controls. When subtyping the sample,
      TD-patients exhibited significantly enhanced indirect semantic priming compared
      with healthy and psychiatric controls as well as NTD-patients. Overall slowing
      was found to be independent of priming effects. Medication, age and chronicity of
      the schizophrenic illness did not modulate priming. CONCLUSIONS: In line with
      Spitzer and Maher it is inferred that disinhibited semantic networks underlie
      formal thought disorder in schizophrenia. For future research, it would be
      appropriate to: employ indirect semantic priming rather than direct semantic
      priming conditions; and, pay more attention to potential moderators of the
      priming effect, most importantly, the prime display duration and the length of
      the stimulus onset asynchrony.

PMID- 11232911
TI  - Schizophrenia-like psychosis following traumatic brain injury: a chart-based
      descriptive and case-control study.
AB  - BACKGROUND: Head injury has been reported to increase the likelihood of the
      development of schizophrenia-like psychosis (SLP), but its features and risk
      factors have been insufficiently investigated. METHOD: Between 1987 and 1997, we
      examined 45 referred patients with SLP following brain trauma. These subjects
      were matched with 45 head-injured subjects without SLP on age (current and at
      injury) and gender, and their case records reviewed systematically. The groups
      were compared and logistic regression analyses performed. RESULTS: The psychoses
      had a mean age of onset of 26.3 years, a mean latency of 54.7 months after head
      injury, usually a gradual onset and a subacute or chronic course. Prodromal
      symptoms were common and depression often present at onset. Paranoid delusions
      and auditory hallucinations were the predominant features, with formal thought
      disorder, catatonic features and negative symptoms being uncommon. The SLP group
      had more widespread brain damage on neuroimaging, especially in the left temporal
      and right parietal regions, and were more impaired cognitively. Fewer (non
      significantly) SLP subjects had epilepsy which was more likely to be well
      controlled in this group. On regression analysis, a positive family history of
      psychosis and duration of loss of consciousness were the best predictors of SLP.
      CONCLUSIONS: Head injury-related psychosis is usually paranoid-hallucinatory and
      subacute or chronic in its presentation. A genetic predisposition to
      schizophrenia and severity of injury with significant brain damage and cognitive
      impairment may be vulnerability factors.

PMID- 11232912
TI  - A functional study of auditory verbal imagery.
AB  - BACKGROUND: We used functional MRI to examine the functional anatomy of inner
      speech and different forms of auditory verbal imagery (imagining speech) in
      normal volunteers. We hypothesized that generating inner speech and auditory
      verbal imagery would be associated with left inferior frontal activation, and
      that generating auditory verbal imagery would involve additional activation in
      the lateral temporal cortices. METHODS: Subjects were scanned, while performing
      inner speech and auditory verbal imagery tasks, using a 1.5 Tesla magnet.
      RESULTS: The generation of inner speech was associated with activation in the
      left inferior frontal/insula region, the left temporo-parietal cortex, right
      cerebellum and the supplementary motor area. Auditory verbal imagery in general,
      as indexed by the three imagery tasks combined, was associated with activation in
      the areas engaged during the inner speech task, plus the left precentral and
      superior temporal gyri (STG), and the right homologues of all these areas.
      CONCLUSIONS: These results are consistent with the use of the 'articulatory loop'
      during both inner speech and auditory verbal imagery, and the greater engagement
      of verbal self-monitoring during auditory verbal imagery.

PMID- 11232913
TI  - Adverse health effects related to mercury exposure from dental amalgam fillings:
      toxicological or psychological causes?
AB  - BACKGROUND: Possible adverse health effects due to mercury released by amalgam
      fillings have been discussed in several studies of patients who attribute various
      symptoms to the effects of amalgam fillings. No systematic relation of specific
      symptoms to increased mercury levels could be established in any of these
      studies. Thus, a psychosomatic aetiology of the complaints should be considered
      and psychological factors contributing to their aetiology should be identified.
      METHODS: A screening questionnaire was used to identify subjects who were
      convinced that their health had already been affected seriously by their amalgam
      fillings (N = 40). These amalgam sensitive subjects were compared to amalgam non
      sensitive subjects (N = 43). All participants were subjected to dental, general
      health, toxicological and psychological examinations. RESULTS: The two groups did
      not differ with respect to the number of amalgam fillings, amalgam surfaces or
      mercury levels assessed in blood, urine or saliva. However, amalgam sensitive
      subjects had significantly higher symptom scores both in a screening instrument
      for medically unexplained somatic symptoms (SOMS) and in the SCL-90-R
      Somatization scale. Additionally, more subjects from this group (50% versus 4.7%)
      had severe somatization syndromes. With respect to psychological risk factors,
      amalgam sensitive subjects had a self-concept of being weak and unable to
      tolerate stress, more cognitions of environmental threat, and increased habitual
      anxiety. These psychological factors were significantly correlated with the
      number and intensity of the reported somatic symptoms. CONCLUSIONS: While our
      results do not support an organic explanation of the reported symptoms, they are
      well in accord with the notion of a psychological aetiology of the reported
      symptoms and complaints. The findings suggest that self-diagnosed 'amalgam
      illness' is a label for a general tendency toward somatization.

PMID- 11232914
TI  - Chronic aircraft noise exposure, stress responses, mental health and cognitive
      performance in school children.
AB  - BACKGROUND: Previous research suggests that children are a high risk group
      vulnerable to the effects of chronic noise exposure. However, questions remain
      about the nature of the noise effects and the underlying causal mechanisms. This
      study addresses the effects of aircraft noise exposure on children around London
      Heathrow airport, in terms of stress responses, mental health and cognitive
      performance. The research also focuses on the underlying causal mechanisms
      contributing to the cognitive effects and potential confounding factors. METHODS:
      The cognitive performance and health of 340 children aged 8-11 years attending
      four schools in high aircraft noise areas (16 h outdoor Leq > 66 dBA) was
      compared with children attending four matched control schools exposed to lower
      levels of aircraft noise (16 h outdoor Leq < 57 dBA). Mental health and cognitive
      tests were group administered to the children in the schools. Salivary cortisol
      was measured in a subsample of children. RESULTS: Chronic aircraft noise exposure
      was associated with higher levels of noise annoyance and poorer reading
      comprehension measured by standardized scales with adjustments for age,
      deprivation and main language spoken. Chronic aircraft noise was not associated
      with mental health problems and raised cortisol secretion. The association
      between aircraft noise exposure and reading comprehension could not be accounted
      for by the mediating role of annoyance, confounding by social class, deprivation,
      main language or acute noise exposure. CONCLUSIONS: These results suggest that
      chronic aircraft noise exposure is associated with impaired reading comprehension
      and high levels of noise annoyance but not mental health problems in children.

PMID- 11232915
TI  - The relationship between job strain and coronary heart disease: evidence from an
      english sample of the working male population.
AB  - BACKGROUND: Many, but not all, studies have reported that job strain is related
      to cardiovascular morbidity and mortality. To date, this relationship has not
      been tested on an English full population sample. This study examines whether the
      demand-control model of job strain contributes to our understanding of the
      determinants of coronary heart disease. METHODS: The analysis uses data from 4350
      working men aged 20-64 in the 1993 Health Survey for England. Job demand and
      control characteristics were determined by questionnaire. Several health outcomes
      were examined: self-rated health; psychiatric health; angina and possible
      myocardial infarction, measured by the Rose questionnaire; doctor-diagnosed heart
      disease; any heart disease. The relationship between job strain and the health
      outcomes was determined by logistic regression analyses after controlling for
      known confounders. RESULTS: Those in high strain jobs consistently reported
      poorer health on all measures than men with lower strain. Similarly, men
      reporting low job strain were least likely to report poor health in 5/6 health
      outcomes. Those with intermediate levels of strain tended to have intermediate
      prevalence rates for poor health. The pattern of association between job strain
      and the CHD was independent of coronary risk factors. CONCLUSIONS: The analyses
      broadly support Karasek's demand-control model of job strain. Health selection
      into low strain jobs may account for the lack of an association between job
      strain and doctor diagnosed heart disease while independent associations between
      job strain and all CHD measures considered together indicate that job strain may
      have aetiological significance for heart disease.

PMID- 11232916
TI  - Adolescent psychological problems, partnership transitions and adult mental
      health: an investigation of selection effects.
AB  - BACKGROUND: Marital status is a strong correlate of psychiatric morbidity in
      adulthood, but debate continues on how far this association reflects causal
      influences or selection effects based on prior psychological characteristics.
      METHOD: Prospective data from the National Child Development Study were used to
      examine effects of adolescent emotional and behavioural problems on transitions
      into and out of first partnerships, and their implications for psychiatric
      morbidity at age 33. RESULTS: Emotional and behavioural problems in adolescence
      showed systematic links with early partnership transitions (age at partnership
      formation, type of first partnership, and risks of first partnership breakdown).
      More detailed tests suggested that these effects only accounted for a modest
      proportion of the associations between partnership status and psychiatric
      morbidity at age 33. CONCLUSIONS: In a non-referred community sample selection
      effects associated with adolescent emotional and behavioural problems appear to
      play only a modest role in links between partnership status and adult mental
      health.

PMID- 11232917
TI  - Social phobia and potential childhood risk factors in a community sample.
AB  - BACKGROUND: This study examined the relationship between potential childhood risk
      factors and social phobia in an epidemiological sample. Identifying risk factors
      such as childhood adversities can often uncover important clues as to the
      aetiology of a disorder. This information also enables health care providers to
      predict which individuals are most likely to develop the disorder. METHODS: Data
      came from the Mental Health Supplement to the Ontario Health Survey of a survey
      of 8116 Canadian respondents, aged 15-64. Social phobia was diagnosed using the
      Composite International Diagnostic Interview (CIDI). Childhood risk factors were
      assessed by a series of standardized questions. RESULTS: A positive relationship
      was observed between social phobia and lack of close relationship with an adult,
      not being first born (in males only), marital conflict in the family of origin,
      parental history of mental disorder, moving more than three times as a child,
      juvenile justice and child welfare involvement, running away from home, childhood
      physical and sexual abuse, failing a grade, requirement of special education
      before age 9 and dropping out of high school. Many of these variables remained
      significant after controlling for phobias, major depressive disorder and alcohol
      abuse. The data also suggest that some childhood risk factors may interact with
      gender to influence the development of social phobia. CONCLUSIONS: Although an
      association was detected between social phobia and childhood risk factors,
      naturalistic prospective studies are needed to clarify the aetiological
      importance of these and other potential risk factors for the disorder.

PMID- 11232918
TI  - Individual-specific risk factors for anorexia nervosa: a pilot study using a
      discordant sister-pair design.
AB  - BACKGROUND: The aim of this pilot study was to examine which unique factors
      (genetic and environmental) increase the risk for developing anorexia nervosa by
      using a case-control design of discordant sister pairs. METHODS: Forty-five
      sister-pairs, one of whom had anorexia nervosa and the other did not, were
      recruited. Both sisters completed the Oxford Risk Factor Interview for Eating
      Disorders and measures for eating disorder traits, and sib-pair differences.
      Blood or cheek cell samples were taken for genetic analysis. Statistical power of
      the genetic analysis of discordant same-sex siblings was calculated using a
      specially written program, DISCORD. RESULTS: The sisters with anorexia nervosa
      differed from their healthy sisters in terms of personal vulnerability traits and
      exposure to high parental expectations and sexual abuse. Factors within the
      dieting risk domain did not differ. However, there was evidence of poor feeding
      in childhood. No difference in the distribution of genotypes or alleles of the
      DRD4, COMT, the 5HT2A and 5HT2C receptor genes was detected. These results are
      preliminary because our calculations indicate that there is insufficient power to
      detect the expected effect on risk with this sample size. CONCLUSIONS: A
      combination of intrinsic and extrinsic factors increases the risk of developing
      anorexia nervosa. It would, therefore, be informative to undertake a larger study
      to examine in more detail the unique genetic and environmental factors that are
      associated with various forms of eating disorders.

PMID- 11232919
TI  - Natural course of symptoms in Cambodia veterans: a follow-up study.
AB  - BACKGROUND: Dutch (ex-)servicemen were deployed in the 1992-3-peace operation
      UNTAC in Cambodia. Since their return, they have voiced concerns about the health
      consequences of their service and they have reported symptoms such as fatigue and
      cognitive problems. The natural course of symptoms in Dutch Cambodia veterans was
      evaluated in a prospective study. METHODS: At 18-months follow-up, a
      questionnaire was sent to 354 veterans who met a set case definition for symptoms
      in Cambodia veterans or who had sub-threshold scores. Initial measurement of
      fatigue severity, psychological well-being, depression, post-traumatic stress
      disorder, trait-anxiety, self-efficacy and causal attributions, was used to
      evaluate predictors for self-reported improvement and low levels of fatigue at
      follow-up. RESULTS: At follow-up, 19% of the respondents reported complete
      recovery, 20% felt much better, 57% had the same complaints and 4% had become
      worse compared with their initial assessment. Self-reported improvement and less
      severe fatigue at follow-up were predicted by less severe fatigue at initial
      assessment and more perceived control over symptoms. CONCLUSIONS: Self-reported
      improvement was reported in a considerable percentage of Cambodia veterans,
      whereas another substantial percentage of Cambodia veterans continued to suffer
      with severe levels of fatigue and related symptoms. Predictors of improvement in
      Cambodia veterans and patients with chronic fatigue syndrome show similarities
      and also seem to bear importance for Gulf War veterans.

PMID- 11232920
TI  - Educational consequences of mental disorders treated in hospital. A 31-year
      follow-up of the Northern Finland 1966 Birth Cohort.
AB  - BACKGROUND: Mental disorders often begin during the formative years of education.
      They may disrupt education and lead to social underachievement. METHODS: We
      examined the impact of mental disorders treated in hospital (ages 16-29) on
      educational attainment up to 31 years in the Northern Finland 1966 Birth Cohort
      (N = 10581). People discharged due to mental illness were grouped by DSM-III-R
      diagnoses (of schizophrenia, other psychoses and non-psychotic disorders) and
      were compared with those having no such hospital treatment. Associations between
      diagnoses and educational outcome (completion of basic level, upper secondary or
      tertiary education) were analysed stratified by age at onset (early onset < 22
      years v. later), and adjusted for confounding by perinatal risk, early motor
      development, maternal education, family structure, parental social class, and
      school achievement using prospective data from earlier assessments and logistic
      regression analysis. RESULTS: Twelve per cent of the comparison group completed
      basic level education, 62% upper secondary, and 26% tertiary education. People
      with early onset disorder tended to stagnate in the basic level. Early onset
      schizophrenia and all non-psychotic cases had 3- to 6-fold adjusted odds for this
      outcome. Many with early onset schizophrenia completed secondary education, but
      none completed the tertiary level. Hospitalization for non-psychotic disorder
      increased the risk of underachievement in tertiary education for those with early
      onset. CONCLUSIONS: Mental disorder treated in hospital truncates education.
      Failure to complete higher education may contribute to the 'social exclusion' of
      the mentally ill through reduced opportunities in later occupational life and
      failure to accumulate social capital.

PMID- 11232921
TI  - The longer term outcomes of community care: a 12 year follow-up of the Camberwell
      High Contact Survey.
AB  - BACKGROUND: There is as yet little evidence available regarding the long-term
      outcomes of people with severe and enduring mental illness who have been cared
      for primarily in the community. METHODS: A 12-year follow-up was carried out of
      the clinical and social problems and needs for care of a group of long-term
      mentally ill patients (N = 81) who were heavy users of psychiatric services when
      originally assessed in the Camberwell High Contact Survey between 1983 and 1985.
      The MRC Needs for Care Assessment Schedule used in the original baseline study
      was repeated at follow-up. RESULTS: The clinical and social functioning of the
      group had remained relatively stable, with high levels of problems and needs at
      both time points and little evidence of significant improvement or deterioration.
      The majority had remained in contact with services. There was some increase in
      levels of unmet as well as met needs, and a decrease in ratings of unmeetable
      needs, which may have been due to changes in clinical practice. CONCLUSION: The
      challenge for current service providers is not only to keep clients stable, but
      also to help improve the clinical and social functioning of people who may no
      longer be the highest priority of current community mental health services. This
      could be approached by identifying the continuing needs of this group, and
      persistently delivering active treatments.

PMID- 11232922
TI  - A preliminary population-based twin study of self-reported eating disorder.
AB  - BACKGROUND: Twin studies have concluded that there is a substantial genetic
      contribution to the aetiology of eating disorders. The aim of the present study
      was to estimate the genetic contribution to the aetiology of self-reported eating
      disorders in a sample of representative twins. METHOD: A population cohort of
      34142 young Danish twins was screened for eating disorders by a mailed
      questionnaire. RESULTS: Concordance rates differed significantly across
      monozygotic and dizygotic twin pairs for broadly defined self-reported anorexia
      nervosa and bulimia nervosa. Heritability estimates of 0.48, 0.52 and 0.61
      respectively were estimated for narrow and broad definitions of self-reported
      anorexia nervosa and for self-reported bulimia nervosa. CONCLUSIONS: There is a
      genetic contribution to the aetiology of self-reported eating disorders in the
      general population. The relationship between self-reported and clinical eating
      disorder remains to be examined.

PMID- 11232923
TI  - Does Beck's Hopelessness Scale really measure several components?
AB  - BACKGROUND: Much of the interest in hopelessness stems from the key role it plays
      in the prediction of suicidal behaviour. To measure hopelessness. Beck el al.
      (1974) developed a 20-item scale (BHS), applied exploratory factor analysis and
      argued that the scale measures three specific components (affective, motivational
      and cognitive). Subsequent exploratory factor analyses identified two, three or
      more factors underlying the scale. METHODS: Several confirmatory factor analyses
      (LISREL) were run on data on 324 suicide attempters in Sweden in order to test
      the hypothesized factorial structures and to investigate the psychometric
      properties of the individual items. RESULTS: Neither three- nor two-factor models
      fitted the data. A simpler structure was sufficient to account for the observed
      correlations between most of the items. This led to the development of several
      variants of a one-factor model, each a combination of affective, motivational and
      cognitive items. The number of items varied between four and 15. CONCLUSIONS: Our
      findings suggest that most of the items (15) of Beck's Hopelessness Scale measure
      one factor. They further suggest that the number of items could considerably be
      reduced. A four-item scale produced an excellent fit. It includes positive and
      negative items describing the perception of the future in terms of success,
      darkness, lack of opportunity and faith. It might even be possible to replace the
      total scale with one item only, 'my future seems dark to me'.

PMID- 11232924
TI  - Evaluation of the zootechnical parameters of vaccinating against swine enzootic
      pneumonia under field conditions.
AB  - A field test was carried out in different production systems to evaluate the
      effect of vaccination against swine enzootic pneumonia with an inactivated
      vaccine. A total of 13,691 pigs of four different genetic origins were used, of
      which 7,351 were vaccinated and 6,340 were used as controls. The animals were
      housed in 16 fattening units, in which the 'one-site', 'two-site' and 'three
      site' production systems were represented. There were the following statistically
      significant differences in favour of the vaccinated animals: a 1.89 per cent
      lower mortality (P<0.001), a 0.09 lower feed conversion ratio (P<0.030), a 3.12
      per cent lower cost per kilogram gained in fattening (P<0.031), a 4.02 per cent
      lower cost per kilogram of carcase (P<0.018), a 3.77 per cent lower cost of feed
      per kilogram gained in fattening (P<0.012) and a 56.75 per cent lower potential
      loss of profit per kilogram gained in fattening due to mortality (P<0.001). An
      analysis of variance of the effects of genetic origin, treatment and production
      system on the different parameters showed that only the treatment had any
      statistically significant effect on the percentage mortality (P<0.002), feed
      conversion ratio (P<0.030), cost per kilogram gained in fattening (P<0.019), cost
      per kilogram of carcase (P<0.020), cost of feed per kilogram gained in fattening
      (P<0.015) and potential loss of profit per kilogram gained in fattening due to
      mortality (P<0.002).

PMID- 11232925
TI  - Efficacy of halofuginone lactate in the prevention of cryptosporidiosis in
      suckling calves.
AB  - The efficacy of halofuginone lactate in the prevention of cryptosporidiosis in
      suckling calves was evaluated in a multicentre, control versus placebo,
      randomised, double-blind clinical trial. Seventy-eight six- to 48-hour-old calves
      were treated daily with 120 microg/kg bodyweight of halofuginone lactate
      administered orally for seven consecutive days, while 80 calves received a
      placebo. Faecal samples were collected on the first day of dosing and four,
      seven, 14 and 21 days later, and Cryptosporidium parvum oocysts were counted and
      faecal indices for diarrhoea were determined after a clinical examination. An
      analysis of variance for repeated measurements showed a highly significant
      difference in favour of halofuginone lactate for both the oocyst counts
      (P=0.0002) and the faecal diarrhoea indices (P=0.0001) throughout the trial. The
      difference was greatest after seven days, when the mean oocyst count of the
      placebo group was 2.5 times and its mean faecal index was twice the mean of the
      halofuginone lactate group. One day after the end of the treatment the calves
      which received halofuginone lactate excreted 44 per cent fewer C parvum oocysts
      and 44 per cent fewer of them had diarrhoea. The reduction was even greater (65
      per cent) when liquid diarrhoea was assessed, with 32.5 per cent of the calves in
      the placebo group having liquid diarrhoea compared with 11.5 per cent in the
      halofuginone lactate group. The treatment was well tolerated and easily
      administered.

PMID- 11232926
TI  - Horner's syndrome following vertical ramus osteotomy in a dog.

PMID- 11232927
TI  - Retrospective study of the effect of superovulation on subsequent fertility in
      embryo-transfer donors.

PMID- 11232928
TI  - Effects of size and storage temperature on meiotic competence of domestic cat
      oocytes.

PMID- 11232929
TI  - Persistent right aortic arch in a mature llama.

PMID- 11232930
TI  - Closure of the Thurso veterinary investigation centre.

PMID- 11232931
TI  - Closure of the Thurso veterinary investigation centre.

PMID- 11232932
TI  - Bulk tank milk failures.

PMID- 11232933
TI  - Ionophore toxicity in turkeys.

PMID- 11232934
TI  - Zoonotic infections in red squirrels.

PMID- 11232935
TI  - Efficacy of fipronil against ticks.

PMID- 11232938
TI  - Lunar influence?

PMID- 11232939
TI  - . . . as BVA calls for action now.

PMID- 11232937
TI  - Lunar influence?

PMID- 11232940
TI  - Coughing in thoroughbred racehorses: risk factors and tracheal endoscopic and
      cytological findings.
AB  - A matched case-control study was made of 100 thoroughbred horses which were
      coughing and 148 control horses which were free of clinical signs of respiratory
      tract disease. The variables identified by multivariable conditional logistic
      regression as being significantly associated with coughing included age (the risk
      decreased with age), the stage of training (horses in early training were at
      greatest risk), the time since the last race (horses that had never raced were at
      greatest risk) and the time since they were last transported (horses transported
      more than 14 days previously were more likely to cough than those transported
      within the last week). The coughing horses were significantly more likely to have
      high scores for upper and lower tracheal mucus and pharyngeal lymphoid
      hyperplasia. In addition, the tracheal aspirates of the coughing horses had
      increased odds of neutrophilia and were more likely to have intracellular
      bacteria than the control horses. However, a considerable proportion of the
      control horses had cytological and/or endoscopic evidence of airway inflammation.

PMID- 11232941
TI  - Radiotherapy for carcinoma of the bladder: a review.
AB  - Carcinoma of the bladder (CaB) is a common and important tumor in North America
      and Western Europe. There has been a steady increase in the incidence of CaB
      during the past 25 years in both of these regions with a simultaneous decrease in
      the mortality rates. The decrease in mortality is primarily due to an earlier
      diagnosis and the availability of more effective therapeutic interventions
      resulting from major advances in surgery and a wide use of multimodality bladder
      preservation therapy.The use of radiotherapy in the management of muscle-invasive
      CaB has undergone a major evolution. External beam radiotherapy alone is used
      infrequently in carefully selected patients. The same applies to the use of
      preoperative irradiation. Brachytherapy alone or combined with external beam
      radiotherapy has been used successfully in Europe but is used infrequently in
      North America. External beam radiotherapy is an essential component of a
      multimodality therapy consisting of cytoreductive surgery via transurethral
      resection of a bladder tumor followed by a planned combination of radiotherapy
      and chemotherapy. The outcomes of this bladder preservation therapy are similar
      to those reported in a like patient population treated with radical cystectomy.
      The main benefit of conservatively treated patients is functioning bladder in
      about 50% of those receiving conservative therapy. Radiotherapy alone or in a
      combination with chemotherapy remains an important and effective palliative
      therapy for patients with recurrent and/or metastatic CaB. Current research
      efforts are directed toward a better identification of important pretreatment
      risk factors predicting failure thus helping in a more optimal selection of
      patients who would benefit most from radical cystectomy or from the application
      of bladder preservation therapy.

PMID- 11232942
TI  - Prediction of node-negative breast cancer outcome by histologic grading and S
      phase analysis by flow cytometry: an Eastern Cooperative Oncology Group Study
      (2192).
AB  - Histologic evaluation and reporting of invasive breast cancer has effectively
      used Nottingham combined histologic grade (NCHG). This approach to predict
      outcome in invasive breast cancer has not been tested in multicenter cooperative
      trials. Histologic slides from selected breast cancer cases entered on node
      negative Eastern Cooperative Oncology Group trials were assigned grades. Two
      pathologists evaluated cases for NCHG defined from differentiation, mitotic
      index, and nuclear grade. The study population consisted of separate samples from
      low- and high-risk strata, where low risk was estrogen receptor positive with a
      tumor size of less than 3 cm and high risk was estrogen receptor negative or
      tumor size greater than or equal to 3 cm. The rate of agreement was generally
      good, with 80% of cases classified the same for mitotic count and 76% of the
      cases classified the same for combined grade. There were no cases disagreeing
      from the lowest to the highest of the three categories. The median follow-up is
      11.6 years, but for analysis of survival, this was truncated at 5 years. Mitotic
      index and combined grade as assessed by both pathologists showed significant
      associations with survival. High combined histologic grade was predictive for
      response to cyclophosphamide/methotrexate/5-fluorouracil (CMF) with survival
      differences at 5 years of 30% in the treated high-grade patients over the
      untreated patients. Overall, it is clear that pathologists can have close
      agreement in assignment of combined histologic grades, with highly significant
      prediction in univariate and borderline significance in multivariate analysis in
      prognostication of time to recurrence as well as survival. Thus, stratification
      used in these trials was highly prognostic as hoped, leaving a role for
      histologic grading in these relatively large tumors, more powerful than S-phase
      analysis in this series. In the subgroups of high-risk patients randomized
      between CMF and observation, there was a suggestion that the high-combined-grade
      group was predictive of treatment efficacy. We conclude that a combined
      histologic grade with defined criteria may be reliably assigned by practiced
      pathologists using readily available criteria, and that the measure may be of use
      in prognostication and prediction of therapeutic responsiveness when done in a
      technically ideal fashion.

PMID- 11232943
TI  - Prospective phase II trial of iriontecan, 5-fluorouracil, and leucovorin in
      combination as salvage therapy for advanced colorectal cancer.
AB  - Irinotecan (CPT11) has established activity in the treatment of advanced
      colorectal cancer without cross-resistance with established 5
      fluorouracil/folinic acid-based therapy. This phase II study was conducted to
      establish the efficacy and tolerance of combination treatment with irinotecan and
      5-fluorouracil as salvage treatment for this disease. Open phase II trial of
      CPT11 180 mg/m2 on day 1, leucovorin 200 mg/m2 on days 1 and 2, and 5
      fluorouracil 400 mg/m2 loading dose followed by 600 mg/m2 infusion on days 1 and
      2. Treatment was continued until progression or limiting toxicity. Responders
      could proceed to surgical resection of residual disease. Thirty-nine patients
      from 2 institutions received a total of 287 cycles of therapy (median 7
      cycles/patient). Eight patients achieved an objective response (7 for liver
      metastasis and 1 for lung metastasis), and an additional 12 obtained
      stabilization of disease or minor responses (MR); of these patients, 8 with liver
      metastasis (7 partial response and 1 MR) underwent hepatic resection of
      metastases and all them obtained a complete response. The median duration of
      response was 14 months, and the median survival was 11 months. Hematologic
      toxicity (neutropenia) was the most common serious side effect (29% of patients
      in 2% of cycles), but significant fever developed in only 4 patients. Grade III
      diarrhea was experienced in at least 1 cycle by 10% of patients. The results of
      this schedule compare favorably with previously reported experience of a phase I
      study designed to establish the dose of CPT11. Efficacy in this poor prognosis
      group of patients is very encouraging, and the schedule is well tolerated by even
      previously treated patients.

PMID- 11232944
TI  - Use of granulocyte colony-stimulating factor after high-dose chemotherapy and
      autologous peripheral blood stem cell transplantation: what is the optimal
      timing?
AB  - Administration of granulocyte colony-stimulating factor to patients undergoing
      high-dose chemotherapy and autologous peripheral blood stem cell transplantation
      accelerates neutrophil recovery and decreases hospitalization time. The optimal
      timing for granulocyte colony-stimulating factor infusion remains unknown. In
      this retrospective, case-controlled, two-armed study, we reviewed our experience
      at Hahnemann University Hospital to determine whether initiating granulocyte
      colony-stimulating factor infusions on posttransplant day 0 versus day 8 affects
      neutrophil recovery time, posttransplant discharge date, total hospital days
      after high-dose chemotherapy, and autologous peripheral blood stem cell
      transplantation. All patients hospitalized between 1994 and 1998 at Hahnemann
      University Hospital, Bone Marrow Transplantation Unit with breast cancer or non
      Hodgkin's lymphoma, who underwent high-dose chemotherapy followed by autologous
      peripheral blood stem cell transplantation and received granulocyte colony
      stimulating factor either on posttransplant day 0 (16 patients) or day 8 (16
      patients). The day 0 and day 8 groups had no statistically significant
      differences in age, sex, weight, height, body surface area, disease
      characteristics, pretransplant harvesting or conditioning regimens, or transplant
      CD34+ cell counts. Our main outcome measure was the mean time to reach absolute
      neutrophil count greater than or equal to 0.5 x 10(9)/l, the number of hospital
      days after transplant, and the total hospital days. The mean days to neutrophil
      recovery (10.56 versus 9.68, p = 0.48), posttransplant hospital days (13.62
      versus 12.81, p = 0.39), and total hospital days (20.25 versus 20.25, p = 1.00)
      were not significantly different between day 8 and day 0 groups, respectively. No
      significant effects on neutrophil recovery time, posttransplant hospital days, or
      total hospital days were observed with the initial granulocyte colony-stimulating
      factor infusion on day 0 versus day 8 after transplant. Delayed administration
      may allow substantial cost savings (US$200 x 8 approximately equal to US $1,600
      per patient) without affecting clinical outcome. More studies are needed to
      determine whether greater delay is feasible.

PMID- 11232946
TI  - Lumpectomy and breast irradiation for breast cancer arising after previous
      radiotherapy for Hodgkin's disease or lymphoma.
AB  - Twelve women treated with radiotherapy with or without chemotherapy for Hodgkin's
      disease (11 patients) and non-Hodgkin's lymphoma (1 patient) and in whom breast
      cancer subsequently developed 10 to 29 years later were treated with lumpectomy
      and breast irradiation. 5,000 cGy/25-30 fractions to the whole breast and 900 cGy
      to 1.000 cGy/5 boost to the operative area. Six also received adjuvant
      chemotherapy for breast cancer. Breast irradiation was well tolerated without any
      unusual acute or chronic sequelae. All women had a good to excellent cosmetic
      result. Ten women are alive and well 1 to 174 months (median: 46) from completion
      of breast irradiation. Two women died with distant metastasis but without local
      recurrence. Breast conservation therapy with radiotherapy is not contraindicated
      in the woman who has previously been treated with radiotherapy for Hodgkin's
      disease or lymphoma.

PMID- 11232945
TI  - Impact of boost technique on outcome in early-stage breast cancer patients
      treated with breast-conserving therapy.
AB  - We reviewed our institution's experience treating early-stage breast cancer
      patients with breast-conserving therapy (BCT) to determine the impact of boost
      technique on outcome. A total of 552 patients with stage I and II breast cancer
      were managed with BCT. All patients were treated with a partial mastectomy and
      radiation therapy (RT). RT consisted of 45 Gy to 50 Gy external beam irradiation
      to the whole breast followed by a boost to the tumor bed using either electrons
      (232 patients), photons (15 patients), or an interstitial implant (316 patients).
      Local control and cosmetic outcome was compared among three patient groups based
      on the type of boost used. Forty-one patients had a recurrence of cancer in the
      treated breast for 5-, 10-, and 13-year actuarial local recurrence rates of 2.8%,
      7.5%, and 11.2%, respectively. There were no significant differences in the local
      recurrence rates or cosmetic outcome using electrons, photons, or an interstitial
      implant. On multivariate analysis, only young age and margin status were
      associated with local recurrence. Stage I and II breast cancer patients
      undergoing BCT can be effectively managed with electron, photon, or interstitial
      implant boost techniques. Long-term local control and cosmetic outcome are
      excellent regardless of which boost technique is used.

PMID- 11232947
TI  - Merkel cell carcinoma arising in the head and neck: optimizing therapy.
AB  - Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine dermal
      neoplasm. Because of the limited number of cases described in the literature
      (approximately 600 to date), statistically significant data regarding treatment
      are difficult to obtain. The majority of MCC cases affect the head and neck and
      are thought to be caused by the actinic damage associated with sun exposure. This
      study evaluates cases of head and neck MCC at Naval Medical Center San Diego
      (NMCSD) and compares the treatment regimens and outcomes from multiple
      institutions. This study is a retrospective outcomes analysis of all cases of
      head and neck MCC seen at NMCSD, between January 1, 1988 and June 30, 1998. The
      records of the NMCSD Tumor Registry were searched for patients with that
      diagnosis, and supplemental information was retrieved from the Radiation Oncology
      and Head & Neck Surgery Clinic charts. Eight of nine patients in this study were
      treated with either wide-local excision or Mohs microsurgery. The surgical
      margins were free of disease in all eight patients. One patient presented with
      distant metastatic disease, and two others were subsequently found to have nodal
      involvement. Subsequent therapy varied among the patients. Survey of the
      available literature revealed inconsistency in terms of which treatment regimens
      are optimal. Tumor resections are recommended by most groups to include a 2-cm to
      3-cm tumor-free margin around the primary lesion when possible, but this is often
      difficult to achieve in the head and neck. Data, which do not reach statistical
      significance, suggest improved outcomes with tumor-free margins. Treatment of the
      regional draining lymph nodes is also recommended in most series. Prophylactic
      lymph node dissection or radiation therapy to the nodal chain may decrease local
      recurrence but does not consistently affect overall survival. Adjuvant
      chemotherapy is advocated by most groups in the treatment of metastatic disease
      because MCC is pathologically similar to small-cell lung carcinoma. However, no
      chemotherapy protocol has been shown to improve survival. Head and neck MCC is a
      rare and aggressive dermal tumor of neuroendocrine origin that requires
      multimodality therapy, including surgery, radiation therapy, and possibly
      adjuvant chemotherapy. Multiinstitutional studies are crucial to obtain
      sufficiently large populations to investigate and optimize therapy in this
      disease.

PMID- 11232948
TI  - Megestrol and tamoxifen in patients with advanced endometrial cancer: an Eastern
      Cooperative Oncology Group Study (E4882).
AB  - To investigate the effect of adding tamoxifen to megestrol in the hormonal
      therapy for advanced endometrial cancer, 66 patients were entered in this study.
      Initially, 41 patients were randomized to either the standard progestin therapy
      of megestrol or to the combination of megestrol and tamoxifen between October
      1982 and October 1984. The megestrol arm was terminated because of poor accrual
      and 25 patients were directly assigned to the combination arm. Among the 20
      eligible cases on the megestrol arm, the response rate of 20% consisted of I
      complete response and 3 partial responses. The response rate on the megestrol
      plus tamoxifen arm was 19% with 1 (2%) complete response and 7 (17%) partial
      responses among 42 eligible cases. The median survival times were 12.0 months and
      8.6 months, respectively. Only mild and moderate toxicities were observed on
      megestrol compared with more toxic complications observed on the combination of
      megestrol and tamoxifen, including a life-threatening case of pulmonary embolism.
      Although we could not carry out a comparative evaluation as intended, we conclude
      that the combination of megestrol and tamoxifen offers no clinical advantage over
      megestrol alone in the treatment of advanced endometrial carcinoma.

PMID- 11232949
TI  - Options for investigative postsurgical therapy for gastric cancer, and case
      report of using the option for combined immunotherapy and chemotherapy.
AB  - The investigative therapy for a senior patient after radical subtotal
      gastroesophagectomy for regional lymph node and proximal esophagus metastasized
      adenocarcinoma (stage IIIA, T3, N 1 M0) of the cardioesophageal junction is
      reported. The case has several unusual features: (1) the patient is the author
      and is not a physician; (2) in the absence of codified postsurgical treatment, he
      used his academic biomedical background, commercial associations, and
      international contacts to find and prioritize six clinically tested options for
      investigative postsurgical therapy; (3) after unsuccessful efforts to append
      ongoing clinical trials of new immunotherapies for breast adenocarcinoma (the
      first two therapy options), an innovative protocol was designed and gained
      allowance by the U.S. Food and Drug Administration for his use of combined
      nonspecific immunotherapy and chemotherapy based on extensive trials in South
      Korea that showed the synergistic effect of the two postsurgical therapies used
      together. A potent, new, nonspecific immunostimulant (DetoxPC) was injected
      subcutaneously in 10 diminishing doses during 105 weeks. Two standard
      chemotherapeutic drugs (5-fluorouracil and mitomycin-C) were injected
      intravenously in six equal doses during three weeks. Five years after the
      surgery, the patient enjoys good health without signs or symptoms of recurrence
      or metastasis. He discusses his perspectives on future clinical trials and on a
      patient actively pursuing investigative postsurgical therapy for a malignancy
      when otherwise poor survival is indicated.

PMID- 11232950
TI  - Absence of major peripheral neuropathy in a phase II trial of ifosfamide with
      vinorelbine in patients with ovarian cancer previously treated with platinum and
      paclitaxel.
AB  - Both ifosfamide and vinorelbine have been shown to produce responses in women
      with previously treated ovarian cancer. However, vinorelbine has been reported to
      cause severe neuropathy in patients previously treated with paclitaxel. We
      assessed a regimen consisting of ifosfamide 1.6 g/m2/d and vinorelbine 30 mg/m2/d
      for 3 days consecutively every 21 days. Because these doses resulted in severe
      neutropenia despite the use of granulocyte colony-stimulating factor, doses were
      reduced to a final level of ifosfamide 960 mg/m2/d and vinorelbine 20 mg/m2/d.
      Peripheral sensory neuropathy was evaluated by questionnaire. A total of 30 women
      were treated. All had previously been treated with both a platinum compound and
      paclitaxel. One partial response was observed among 23 patients with measurable
      disease, and two CA-125 responses were noted among seven patients without
      measurable disease. Severe progressive neurotoxicity was not observed. Despite
      the fact that almost half the patients had not been exposed to cyclophosphamide,
      this regimen produced few responses. Superior response rates have been reported
      with single-agent vinorelbine at doses that do not require growth factor support.
      With this dose and schedule, vinorelbine is reasonably safe therapy for patients
      who have received prior paclitaxel and who have have mild baseline sensory
      neuropathy.

PMID- 11232951
TI  - Chemotherapy for acute myelogenous leukemia in the elderly with cytarabine,
      mitoxantrone, and granulocyte-macrophage colony-stimulating factor.
AB  - Remission induction chemotherapy for acute myelogenous leukemia typically
      combines cytarabine with an anthracycline or anthracycline derivative. To date,
      no specific combination has emerged as more efficacious than any other. To reduce
      toxicity and shorten the duration of neutropenia, hematopoietic growth factors
      are often added to the chemotherapy regimen, especially in elderly patients. In
      all prospective, randomized, growth factor trials to date, daunorubicin has been
      the drug selected for combination with cytarabine. We hypothesized that
      mitoxantrone might be as efficacious in this patient population with perhaps less
      toxicity when combined with granulocyte-macrophage colony-stimulating factor (GM
      CSF). Patients older than age 55 years with a diagnosis of either de novo or
      secondary, untreated acute myelogenous leukemia were eligible for this clinical
      trial. Eligible patients were treated with cytarabine 100 mg/m2 infused as a
      continuous infusion daily for 7 days and mitoxantrone 12 mg/m2 bolus
      intravenously for the first 3 days of cytarabine. A second cycle of chemotherapy
      was administered on the fourteenth day of treatment if marrow aplasia was not
      achieved with the first cycle. Once aplasia was achieved, GM-CSF 250 microg/m2
      was given subcutaneously daily until neutrophil recovery. Those patients who
      achieved complete remission were treated with two cycles of intermediate-dose
      cytarabine (400 mg/m2 daily for 5 days) and with GM-CSF as consolidation therapy.
      Of the 30 patients treated, the median age was 69 years (range: 55-76 years) and
      18 patients were older than 65 years of age. Seven (23%) patients had secondary
      acute leukemia and 12 (40%) had poor-risk cytogenetics. Nineteen (63%) achieved a
      complete remission. Eleven patients were either refractory to treatment or died
      during their treatment. The toxicity encountered was no more than that reported
      in similar studies using daunorubicin in combination with cytarabine. Long-term
      survival was poor, with a median disease-free survival of only 8.1 months in
      patients who achieved complete remission. In this elderly population of patients
      with high-risk acute myelogenous leukemia, this combination of cytarabine,
      mitoxantrone, and GM-CSF resulted in an adequate remission rate with acceptable
      toxicity. Long-term survival, however, was poor and innovative treatment
      approaches to maintain remission are needed.

PMID- 11232952
TI  - Lack of efficacy of topotecan in the treatment of metastatic or recurrent
      squamous carcinoma of the head and neck: an Eastern Cooperative Oncology Group
      Trial (E3393).
AB  - Recurrent or metastatic squamous carcinoma of the head and neck (RMSCHN) is a
      modestly chemoresponsive tumor; however, currently available agents have failed
      to improve survival. New active agents are needed for the treatment of this
      disease. Topotecan is a topoisomerase inhibitor that demonstrated initial
      promising activity in squamous carcinoma of the head and neck. The Eastern
      Cooperative Oncology Group conducted a phase II trial of topotecan to determine
      the efficacy and toxicity of a weekly treatment schedule in patients with RMSCHN.
      Patients with metastatic or locally recurrent squamous carcinoma of the head and
      neck were treated with topotecan 1.5 mg/m2 x 24 hours by continuous infusion on
      days 1, 8, 15, and 22 of each 35-day cycle. Patients were stratified in two
      cohorts: chemonaive and previously treated. Sixteen chemonaive and 16 previously
      treated patients were registered on study. Grade III/IV neutropenia and anemia
      occurred in 16% and 18% of patients, respectively. No responses were observed in
      either cohort. Median survival for previously untreated patients was 4.6 months
      and 3.2 months for previously treated patients. Topotecan failed to demonstrate
      efficacy in patients with RMSCHN. Further evaluation of this agent is not
      planned.

PMID- 11232953
TI  - Malignant lymphoma of mucosa-associated lymphoid tissue of the lacrimal gland:
      case report and review of literature.
AB  - Mucosa-associated lymphoid tissue (MALT) lymphomas are increasingly recognized as
      a distinct clinical-pathologic entity among the non-Hodgkin's lymphomas. It
      usually presents as a localized disease process in extranodal tissues or organs
      such as stomach, salivary gland, thyroid gland, and not infrequently in orbital
      adnexa. Radiotherapy has an important role in the management, although long-term
      clinical results specifically addressing localized MALT lymphomas are lacking. We
      report a case of localized MALT lymphoma of the lacrimal gland, with successful
      treatment by radiation therapy (total dose 25 Gy) with 3 years of clinical follow
      up. A review of the published literature was undertaken to assess the role of
      radiotherapy in the treatment of this disease involving orbital tissues,
      specifically, the lacrimal gland. Based on previous reports of patients with
      orbital lymphomas (low grade) and pseudolymphomas, of which many will now be
      recognized as MALT lymphomas, radiotherapy has an excellent local control rate
      and would be the treatment of choice. However, long-term results of
      pathologically confirmed cases of MALT lymphomas need further study because
      occasional relapses at distant sites can occur.

PMID- 11232955
TI  - Osteoclastic giant cell tumor of the pancreas: case report and literature review.
AB  - An unusual case of a 40-year-old woman seeking treatment for a 10-cm cystic
      neoplasm of the pancreas is described. Imaging revealed a large proteinaceous,
      fluid-filled cyst with a mural nodule. Laparotomy was successful with en bloc
      resection. Pathologic examination revealed a neoplastic mucinous epithelial tumor
      with an abundance of multinucleated tumor giant cells. This presentation is
      consistent with literature reports of an osteoclastic-type giant-cell tumor of
      the pancreas. The natural history, pathologic evaluation, and clinical
      implications of this rare neoplasm are discussed with reference to published
      reports.

PMID- 11232954
TI  - Concurrent chemoradiotherapy for oropharyngeal carcinoma.
AB  - The clinical results of definitive chemoradiotherapy for oropharyngeal carcinoma
      were retrospectively analyzed. Thirty-one patients with oropharyngeal carcinoma
      who received definitive radiation therapy between January 1986 and June 1998 were
      analyzed. The median age was 61 years. All patients had squamous cell carcinoma.
      According to the Union International Contre le Cancer 1997 classification system,
      stage I, II, III, IVA, and IVB were 1,0, 9, 14, and 7, respectively. Regarding
      the primary site, 23 tumors were in the lateral wall, whereas 2 were in the
      superior wall, and 3 each were in the anterior and posterior walls. The median
      total dose was 66 Gy, with a range of 60 Gy to 74.4 Gy. The overall treatment
      time ranged from 39 days to 113 days, with a median of 50 days. Seven patients
      underwent hemilateral radical neck dissection. Fourteen patients received
      concurrent chemotherapy using weekly cisplatin (50 mg/d) at least three times.
      The 5-year overall and cause-specific survival (CSS) rates were 55% and 62%,
      respectively. All local recurrences occurred within 2 years. The CSS rate in
      patients with lateral or superior wall origin was significantly superior to that
      of patients with anterior or posterior wall origin (p < 0.05). The 3-year CSS
      rate was 83% for patients treated with concurrent chemoradiotherapy using weekly
      cisplatin at least 3 times, whereas that was 53% for the remaining patients (p <
      0.05). No serious adverse effects were observed. It is concluded that definitive
      concurrent chemoradiotherapy using weekly cisplatin for oropharyngeal carcinoma
      appear promising.

PMID- 11232956
TI  - Brain metastasis from a primary liposarcoma of the digit: case report.
AB  - Soft-tissue sarcomas of the digit are uncommon. We herein report on a patient
      with a de-novo subungual right thumb liposarcoma with subsequent failure in the
      brain. The pertinent literature and recommendations for management are presented.

PMID- 11232957
TI  - Bilateral primary breast lymphoma.
AB  - A primary breast lymphoma developed in a patient. After 139 months. she was
      diagnosed with a new primary breast lymphoma in the contralateral breast. The
      pathologic diagnosis in each tumor was non-Hodgkin's lymphoma, B-cell, diffuse
      large cell. Radiation therapy was effective in securing a clinical remission for
      both tumors.

PMID- 11232958
TI  - Two patients with N3 bladder cancer successfully treated by internal iliac
      arterial infusion chemotherapy and irradiation: case reports.
AB  - The prognosis of patients with bladder cancer with pelvic lymph node metastasis
      is poor, and only 30% of them have been reported to achieve 5- and 10-year
      survival rates. Prognosis of the patients with pelvic lymph node metastasis
      larger than 5 cm (N3) is especially poor. and no patient has been reported to
      have survived more than 3 years. The authors report the successful treatment of
      two patients with pelvic N3 bladder cancer by internal iliac arterial infusion
      chemotherapy combined with whole-pelvis irradiation.

PMID- 11232959
TI  - Pilot study of concurrent 5-fluorouracil/paclitaxel plus radiotherapy in patients
      with carcinoma of the esophagus and gastroesophageal junction.
AB  - Preoperative concurrent chemotherapy and radiotherapy can be highly effective but
      are often associated with significant rates of morbidity and even mortality. We
      studied the toxicity of continuous infusion of 5-fluorouracil (5-FU) and weekly
      paclitaxel combined with radiotherapy. Patients had histologic proof of local
      regional carcinoma of the esophagus or gastroesophageal (GE) junction, a
      Karnofsky performance status of 70 or greater, and normal liver, renal, and bone
      marrow functions. Chemotherapy consisted of continuous infusion of 5-FU (300
      mg/m2/d) for 5 days a week for 5 weeks, plus paclitaxel (45 mg/m2) given during 3
      hours every week for 5 weeks. Based on the tumor location and its resectability,
      the total dose of concurrent radiation varied between 45 Gy and 50.4 Gy. Nine men
      and one woman, with a median age of 61 years, were evaluated. One had GE junction
      cancer, six had distal esophageal cancer, and three had midesophageal cancer.
      Weight loss, nausea, vomiting, and dysphagia of grades I and II were noted. The
      hematologic toxicity was mild. No patients required transfusion. There was no
      leukopenia or thrombocytopenia. None of the patients was hospitalized during
      chemoradiation; all patients completed treatment as outpatients. Five patients
      had subsequent surgical resections: one had a pathologically complete response,
      and two had a partial response (>90% necrosis). Continuous infusion of 5-FU plus
      paclitaxel given concurrently with radiotherapy was well tolerated. We plan to
      study this regimen further in upper gastrointestinal cancers.

PMID- 11232960
TI  - Phase II study of liposomal doxorubicin in patients with advanced colorectal
      cancer.
AB  - Doxil is a liposomal preparation of doxorubicin that results in prolonged
      pharmacologic exposure in vivo to the active agent. We sought to test the
      hypothesis that this new formulation would result in improved efficacy in
      patients with colorectal cancer. Patients with advanced colorectal cancer who had
      received prior therapy were eligible for the trial. Treatment consisted of Doxil
      45 mg/m2 intravenously every 3 weeks. Seventeen patients entered the trial and
      they received a median of two cycles of treatment. None of the patients had a
      partial response to treatment. Stable disease was the best response, and one
      patient received therapy for 17 cycles before her disease progressed. The therapy
      was well tolerated, with only two patients having the dose decreased because of
      hand-foot syndrome. Four patients experienced allergic reactions during the
      infusion, but with appropriate premedication and slowing of the infusion,
      treatment was able to be resumed without difficulty. No greater than grade I
      neutropenia or thrombocytopenia developed in any patient. Although Doxil was well
      tolerated at this dose and schedule, it was not an active agent in this group of
      patients. Doxil alone or in combination with other agents is worthy of further
      study in cancers responsive to doxorubicin.

PMID- 11232961
TI  - Clear cell carcinoma of the ovary: a remarkable case.
AB  - Clear cell carcinoma of the ovary is uncommon, and there are few reports of
      successful long-term therapy. In this case report, a previously healthy
      preadolescent presented with clear cell carcinoma of the ovary. After progressing
      through two regimens of chemotherapy, she was given topotecan, which arrested the
      disease. Nearly 3 years later, she continues to lead a near-normal life as a high
      school student. Our treatment plan is to continue to administer this therapy at
      monthly intervals until relapse. Although the achievement of stable disease with
      topotecan is frequently observed in patients relapsing with epithelial ovarian
      cancer, durable stable disease in clear cell carcinoma of the ovary is unusual.
      Treatment--and long-term maintenance therapy--with topotecan may be an option in
      such patients. In this case, the lack of cumulative toxicities allows the patient
      to maintain her usual daily activities.

PMID- 11232962
TI  - Long-term results after myectomy in 64 patients with hypertrophic obstructive
      cardiomyopathy (HOCM). Morphological and hemodynamic aspects.
AB  - BACKGROUND: The aim of this study was to observe the changes in left-ventricular
      morphology, the improvement in hemodynamics and the survival curves (according to
      Kaplan-Meier) of patients following transaortic myectomy. METHODS: From November
      1985 to August 1997, transaortic myectomy according to Morrow's proposal was
      carried out at the Heart Center NRW in Bad Oeynhausen in 64 patients with
      isolated HOCM. At the time of operation, the patient group included 33 women and
      31 men aged between 14 and 76 years (mean 52.56 years). A hemodynamically
      relevant aortic stenosis was excluded in all patients. Sixty-three patients
      (98.4%) were evaluated in total over a mean observation period of 4.6 years (4
      months to 12 years). One patient lost touch with our hospital RESULTS: The
      clinical symptoms according to NYHA grade could be improved postoperatively from
      3.4 +/- 0.33 to 1.36 +/- 0.6 (p < 0.001). The echocardiographic preoperative
      pressure gradient between the left ventricle and the aorta was 73.2 +/- 14.8 mmHg
      at rest and 139.6 +/- 21.2 mmHg after provocation by ventricular premature beats
      (VPBs). Postoperatively, the gradient was reduced significantly: 13.56 +/- 2.7
      mmHg at rest and 23.3 +/- 10.7 mmHg after VPBs, respectively (p < 0.001).
      Perioperative complications occurred in 12 patients including 1 early death due
      to low-output syndrome, corresponding to an early mortality rate of 1.6%. Four
      patients died within a postoperative period of 1 year to 9.5 years, none of them
      due to cardiac causes, 2 due to non-cardiac causes and 1 of unknown causes. In 2
      patients a recurrent HOCM occurred at 7 and 10 years after the myectomy and they
      were treated by catheter intervention with the alcohol induced septal infarction.
      CONCLUSIONS: Based on the 12-year survival rate of 76.640% in our study,
      transaortal myectomy according to Morrow represents a safe and reliable form of
      therapy, with relatively low perioperative mortality and complication rates, also
      in the long-term

PMID- 11232963
TI  - Importance of heart rate for acute hibernation in isolated blood-perfused piglet
      hearts.
AB  - BACKGROUND: Hibernating myocardium may benefit from revascularization. There are
      several experimental models for acute hibernation. In intact hearts low-flow
      ischemia causes time-dependent metabolic alterations, termed "metabolic
      adaptation". In isolated heart preparations metabolic responses to low-flow
      ischemia vary, and signs of metabolic adaptation are not consistently found. In
      isolated hearts global ischemia may cause bradycardia unless the hearts are
      paced. We hypothesized that the lack of consistent metabolic adaptation to low
      flow ischemia in isolated hearts might be due to bradycardia during ischemia. In
      this study we investigated the influence of heart rate on metabolism and function
      in an isolated heart preparation. METHODS: Isolated blood-perfused piglet hearts
      were subjected to 120 min 10% flow. In groups A (n=9) and B (n=4) hearts were not
      paced during ischemia, in groups C (n=5) and D (n=5) hearts were paced at pre
      ischemic heart rate during ischemia. RESULTS: Without pacing, heart rate declined
      to approximately 1/3 during ischemia and anaerobic metabolism showed a slight
      decline over time. With pacing, production of protons, pCO2 and lactate showed a
      bell-shaped curve which peaked at 20-25 min of ischemia, followed by a subsequent
      decline towards the end of ischemia (overall p < 0.001 for all). However,
      reperfusion revealed impaired recovery of function in paced hearts compared to
      non-paced hearts (53 +/- 7% vs 77 +/- 4%, p < 0.05) concomitant with higher
      release of creatine kinase (455 +/- 93 IU/100 g vs 106 +/- 13 IU/100 g, p <
      0.01). CONCLUSIONS: When heart rate is allowed to decline during low-flow
      ischemia in isolated piglet hearts, signs of metabolic adaptation are not
      evident. When hearts are paced during ischemia time-dependent alterations in
      anaerobic metabolism occur, resembling observations seen in intact beating
      hearts. However, paced hearts also show indications of increased cellular injury,
      indicating that in paced hearts the metabolic consequences are mostly due to
      increased irreversible cell injury. Thus, the model for acute hibernation with
      10% flow in isolated blood-perfused piglet hearts are critically dependent on
      bradycardia during ischemia.

PMID- 11232964
TI  - Effect of normothermic versus hypothermic cardiopulmonary bypass on cytokine
      production and platelet function.
AB  - BACKGROUND: Proinflammatory cytokines and platelets play a key role in the
      systemic inflammatory response associated with cardiopulmonary bypass (CPB). The
      aim of this study was to evaluate the effects of both hypothermic and
      normothermic CPB on platelet activation, cytokine production, as well as their
      possible correlations. METHODS: Twenty patients who underwent CABG were randomly
      assigned into two groups receiving hypothermic and normothermic CPB. Blood
      samples were obtained through a venous catheter at 6 time points. The following
      parameters were measured: in vitro platelet aggregation, in vivo platelet
      activation, complete and differential blood cell counts, plasma soluble P
      selectin levels, plasma IL-6, IL-1beta and TNFalpha levels. RESULTS: The results
      demonstrated that platelet abnormalities could be observed to a greater extent
      during hypothermic rather than normothermic CPB. The occurrence of in vivo
      platelet activation was suggested by the presence of a significantly increased
      percentage of platelets expressing CD62P on their surface, as well as by a
      decreased in vitro platelet aggregation induced by different agonists. Complete
      and differential blood cell counts showed no substantial decrease in platelet
      number without differences between groups. The results obtained also showed the
      presence of a significant release of sP-selectin during CPB, as well as a more
      pronounced increase of plasma sP-selectin levels in patients undergoing
      hypothermic compared to normothermic CPB. A comparison of cytokine levels
      demonstrated a significant elevation of plasma IL-6 levels during either
      hypothermic or normothenmic CPB, paralleling the neutrophil rise, while no
      differences were observed for TNF-alpha levels. Conversely, plasma IL-1beta
      levels were significantly elevated during hypothermic, but not during
      normothermic CPB. CONCLUSIONS: Hypothermic CPB is responsible for a greater
      platelet activation and endothelial dysfunction than normothermic CPB, leading to
      more profound changes in the hemostatic and inflammatory systems, which, in turn,
      might be responsible for the higher incidence of postoperative complications
      reported during hypothermic CPB.

PMID- 11232966
TI  - Atrial ablation using an IRK-151 infrared coagulator in canine model.
AB  - BACKGROUND: A method of atrial ablation was developed with the aim of shortening
      the aortic cross-clamp time during MAZE surgery. The IRK-151 infrared coagulator
      (Infrarot-Kontaktkoagulator: MBB: Messerschmidt-Bolkow-Blohn, Germany) was
      employed. Our aim was to electrophysiologically confirm the efficacy of this
      device. METHODS: The MAZE-III procedure was performed in four mongrel dogs.
      Instead of a pulmonary vein-encircling incision, IRK-151 was applied several
      times to create a continuously overlapping circular lesion. After aortic
      declamping, the potentials of both atria were recorded using 18 bipolar
      electrodes implanted in the atrial wall. The recording conditions were: 1) sinus
      rhythm, 2) overdrive pacing from outside the encircling coagulation, and 3)
      overdrive pacing from inside the encircling coagulation. RESULTS: 1) There was no
      detectable potential within the pulmonary vein-encircling coagulation. 2) There
      was no conduction of paced atrial potential inside the encircling coagulation. 3)
      Only the area within the encircling coagulation was activated by the stimulus.
      Other parts of the atrium showed sinus rhythm simultaneously. CONCLUSIONS: The
      left atrium within the pulmonary vein-encircling coagulation was isolated
      electrophysiologically.

PMID- 11232965
TI  - Ischemic cardiovascular disease and Helicobacter pylori. Where is the link?
AB  - Coronary heart disease (CHD) is the leading cause of death in western countries.
      Although several major risk factors have been identified, they fail to account
      for all the epidemiological variants of the disease, thus warranting research
      into novel causal agents. Cardiovascular diseases have long been associated with
      chronic infections acting through the activation of inflammatory pathways, and
      antibiotic therapy has been shown to produce a dramatic decrease in the rate of
      disease recurrence in patients with a history of myocardial infarction or
      unstable angina. The link between Helicobacter pylori (H. pylori) infection and
      CHD, first described by Mendall et al. in 1994, has been the subject of a
      multitude of epidemiological and clinical studies; however, these have been so
      heterogeneous that not two of them are based on a comparable selection of
      patients and focused on the same kind of disease, e.g. stable coronary heart
      disease or acute myocardial infarction. Evidence from animal studies supports the
      thesis that H. pylori plays an extremely important role in the acute phase of
      myocardial infarction: the bacterium causes platelet aggregation and induces pro
      coagulant activity in experimentally infected mice. H. pylori may also contribute
      to atherosclerosis through an auto-immune process against endothelial cells or an
      increased concentration of homocysteine in the blood due to decreased levels of
      folic acid and cobalamin. The exact role of H. pylori cannot yet be fully
      assessed: there is a clear and present need for further studies with appropriate
      epidemiological and clinical approaches to investigate through prospective and
      interventional trial the possible causal relationship between H. pylori and CHD.

PMID- 11232967
TI  - Leukocyte activation during cardiopulmonary bypass: limitations of the inhibitory
      mechanisms and strategies.
AB  - Cardiopulmonary bypass, initiates a generalised response, which is primarily
      defensive in nature. This response is self regulated and terminated
      spontaneously. Obvious problems are complement and leucocyte activation, but
      several other cascades are also stimulated, which interact, accentuate or
      modulate this response. These supporting cascades include, release of
      inflammatory cytokines, an activation of kallikrein system, clotting and
      fibrinolytic mechanisms, and arachidonic acid metabolism. Because of an effective
      autoregulatory mechanism, only a small proportion of patients (<3%), undergoing
      cardiopulmonary bypass are adversely effected by this process. Prognosis of these
      patients is often unpredictable, but in general, high risk patients are likely to
      suffer most. A number of specific and non specific artificial measures have been
      introduced to control postperfusion problems, resulting from this process. These
      control measures are usually effective against a specific component of this
      generalised problem, and often fail to achieve desired effects. Efficacy of
      control measures is further limited by a continued activation of complement and
      leucocytes, via interactions between the mentioned inflammatory cascades. In view
      of these limitations, we have introduced certain modifications in our previously
      reported control strategy. These include an early identification of high risk and
      susceptible individuals and using specific inhibitors of complement activation
      for both initial and terminal stages.

PMID- 11232968
TI  - Neonatal repair of anomalous origin of the right pulmonary artery from the
      ascending aorta. A case report and review in the literature.
AB  - A seven-day-old neonate presented with respiratory distress and an early
      diagnosis was achieved through the echocardiographic studies which successfully
      visualized an anomalous origin of the right pulmonary artery arising from the
      ascending aorta. Subsequently a surgical correction with direct anastomosis of
      the right pulmonary artery to the main pulmonary trunk was accomplished in the
      neonatal period. The English literature in the last two decades is reviewed to
      discuss the characteristics, the diagnosis and treatment of neonatal cases with
      anomalous origin of the right pulmonary artery arising from the ascending aorta.

PMID- 11232969
TI  - Newer developments in endovascular graft treatment for aortic and aortoiliac
      aneurysms. A seven-year experience.
AB  - BACKGROUND: This article described a 7-year experience with endovascular graft
      for the tratment of aortoiliac aneurysms and other arterial lesions. METHODS:
      Four hundred and seventy-two grafts of various types have been placed in 283
      patients. RESULTS: Short and mid-term results in these patients suggest that
      endovascular grafts may provide better treatment for central artery injuries and
      some iliac and aortoiliac aneurysms, particularly in high-risk patients and those
      with previous aortoiliac surgery. CONCLUSIONS: In other circumstance, long-term
      evaluation will be required to determine the effectiveness and limitations of
      these endovascular grafts.

PMID- 11232970
TI  - Percutaneous endovascular treatment of peripheral aneurysms.
AB  - BACKGROUND: To evaluate the feasibility and efficacy of percutaneous endovascular
      treatment of peripheral aneurysms. METHODS: Forty-eight patients, M: 41, F: 7,
      mean age: 65.7 +/- 10.1 years (47-85 years), with 50 aneurysms were treated: 45
      with covered stents (Cragg/Passager 22, Corvita 21, Wallgraft 1, Endotex 1) 4
      with non-covered stents and 1 with stent graft. Twenty-six aneurysms located at
      the iliac artery, 12 at the femoral and 12 at the popliteal artery. Mean lesion
      length: 61.1 +/- 21.3 mm. Percutaneous approach used in all cases, femoral
      antegrade (n=24), retrograde (n=23), contralateral (n=2), popliteal (n=1). Stents
      used were 6-12 mm in diameter and 30-120 mm in length. Multiple stents used to
      cover all lesions in 20 cases. RESULTS: Immediate technical success was 96%
      (48/50). In 1 case of long, tortuous femoropopliteal aneurysm, it was impossible
      to cover the low part, due to rigidity of the device used, in 1 case of large
      iliac aneurysm there was incomplete immediate exclusion. No complication during
      the procedure. Four patients developed non-infectious fever/local pain. Eight
      thromboses occurred: 2 at iliac, 1 at femoral and 5 at the popliteal level. All
      other stents remained patent, the aneurysms completely excluded over a mean
      follow-up of 20.6 +/- 13.2 m, maximum 61 m. Primary patency: all lesions 82%,
      iliac 92%, femoropopliteal 78%. Secondary patency: all lesions 88%, iliac 96%,
      femoropopliteal 86%. CONCLUSION: Percutaneous endoluminal treatment of peripheral
      aneurysms seems safe and effective with high technical success and good long-term
      results, except for popliteal localization. It could be an alternative to
      surgery.

PMID- 11232971
TI  - Biological response to expandable metallic stents implanted into the portal vein.
      A histomorphometric study.
AB  - BACKGROUND: This study was undertaken to investigate the biological response to
      an expandable metallic stent implanted in the canine portal vein with a special
      reference to the histomorphometric contribution of cellular and acellular
      elements to the intimal and medial growth. METHODS: In 11 dogs, the Gianturco Z
      stent was placed into the portal vein and was harvested at intervals of 4 (n=6)
      and 12 weeks (n=5). In 6 dogs, the normal portal vein was harvested and used as a
      control. The specimens were subjected to histomorphometric examination. RESULTS:
      Mean intimal/medial thickness and total intimal/medial area significantly
      increased progressively by 12 weeks. Collagen intimal/medial area also
      significantly increased progressively by 12 weeks, while smooth muscle
      intimal/medial area significantly increased at 4 weeks but did not change from 4
      weeks to 12 weeks. Collagen density tended to increase at 4 weeks and
      significantly increased at 12 weeks, while smooth muscle density significantly
      decreased at 4 weeks and continued to decrease at 12 weeks. CONCLUSIONS: The
      total area or mean thickness of the intima and media of the stented portal vein
      continued to increase by 12 weeks after stent placement. This phenomenon appeared
      to be due to proliferation of smooth muscle cells followed by accumulation of
      collagen.

PMID- 11232972
TI  - Peripheral vascular brachytherapy: an introduction.
AB  - The response of cells to ionising radiation has been extensively studied for the
      past 30 years. When radiation is absorbed in biological material, it can directly
      ionise a critical site (direct effect) or interact with other molecules to
      produce reactive free radicals, which can subsequently damage critical biological
      molecules (indirect effect). DNA is considered the critical target damaged by
      ionising radiation by both direct and indirect processes. Since radiotherapy had
      proven to be effective in the treatment of non-malignant proliferative processes,
      it was assumed that this adjunctive treatment would also inhibit vascular
      restenosis. The major difference between external and intravascular radiation is
      dose distribution. Intravascular delivery results in extremely high doses to the
      lumen with a fall-off in dose as a function of distance from the source; whereas,
      external beam would deliver a uniform dose over the entire volume of tissue
      treated. Unlike in the coronary circulation most of the peripheral vessels
      treated are greater than 3 mm in diameter; in fact many are 7 to 10 mm in
      diameter. Since beta radiation is related to lower penetration properties and
      more heterogeneous distribution of radiation in comparison to gamma radiation, it
      is therefore necessary to use a gamma radiation source because it would be
      difficult to irradiate the sub-intimal tissue with a beta source centred in a
      large vessel. Radiation can and does have the potential to destroy blood vessels.
      The challenge in vascular brachytherapy is to treat blood vessels to a point
      where restenosis is inhibited; yet the vessel is not irreparably damaged.

PMID- 11232973
TI  - Piezoelectric pulse sensor device (Pulse Chek)-monitoring after the treatment of
      lower leg ischemia.
AB  - BACKGROUND: The aim of this study was to evaluate the usefulness of the
      piezoelectric pulse sensor device (Pulse Chek) as a continuous monitoring method
      in early surveillance after the treatment of lower leg ischemia with either
      surgical or interventional procedures. METHODS:  EXPERIMENTAL DESIGN: prospective
      study. SETTING: institutional practice. PATIENTS AND INTERVENTIONS: two patient
      groups with peripheral arterial occlusive disease were included; a surgical group
      undergoing femoropopliteal bypass grafting (22 patients) and a group undergoing
      PTA of the femoral or popliteal arteries (18 patients). MEASURES: the
      piezoelectric pulse sensor was applied on the skin over the dorsalis pedis
      artery. A baseline waveform was recorded preoperatively and continuous monitoring
      begun immediately after the surgical or interventional procedure. Hard copy
      recordings of the pulse wave were done in the immediate postoperative period, the
      postoperative evening, the following morning or at any time the alarm was
      triggered. A late follow-up waveform was recorded after an average of 34 days.
      Simultaneous ABI measurements were recorded. RESULTS: Preoperatively or pre
      intervention, the pulse waveform was accurately recorded in 15/22 (68%) patients
      in the surgical group and 14/18 (78%) patients of the PTA group. In 20 (91%)
      surgical group patients and in 14 (78%) PTA group patients, postoperative
      monitoring was reliable, the pulse waveform confirmed patency of the vessel.
      Piezoelectric pulse sensor device monitoring did not detect graft occlusion in
      only one patient in the surgical group where interpretation of the pulse wave was
      complicated by a slow atrial fibrillation. There were 19 alarms in the pulse
      waveform during monitoring for 11 (55%) surgical group patients and 18 alarms for
      9 (64%) PTA group patients. None of the alarms resulted from graft occlusion.
      Reliable pulse waveform recordings were obtained in 16/21 (76%) surgical group
      patients of the original 22 (one graft occluded) and for 15/18 (83%) PTA group
      patients in the follow-up assessment after the mean 34 days. One surgical patient
      was lost to follow-up. CONCLUSIONS: The piezoelectric pulse sensor device can be
      recommended as a method of continuous monitoring immediately after the
      revascularization procedure in those patients who have a pedal artery where a
      reliable pulse waveform can be recorded.

PMID- 11232974
TI  - Multivariate analysis of long-term results after an axillobifemoral and
      aortobifemoral bypass in patients with aortoiliac occlusive disease.
AB  - BACKGROUND: Controversy still remains regarding the long-term results and
      indications for axillofemoral bypass (AxFB). A comparison of axillobifemoral
      bypass (AxBFB) and aortobifemoral bypass (ABFB) was thus conducted to determine
      whether AxFB is an acceptable alternative vascular procedure to anatomic bypass
      for high-risk patients. METHODS: Sixty-three patients who underwent a total of 25
      AxBFBs and 38 ABFBs for aortoiliac occlusive disease were reviewed
      retrospectively, and both univariate and multivarate analyses were perfomed.
      RESULTS: The overall survival was 82.8% at five years. A univariate analysis
      revealed significantly lower survival rates for patients with limb-threatening
      ischemia, coronary disease, and cerebrovascular disease. A multivariate analysis
      disclosed no significant factors influencing survival rates. The overall primary
      patency was 79.8% at five years. The primary patency rates for AxBFB (67.7% at
      five years) were significantly lower than for ABFB (88.5% at five years) based on
      a univariate analysis (p=0.0045). In addition, the secondary patency rates for
      AxBFB (80.3% at five years) were significantly lower than for ABFB (96.5% at five
      years, p=0.0025). A multivariate analysis disclosed significantly lower primary
      patency rates for grafts with a higher angiographic outflow score and
      simultaneous infrainguinal reconstructive procedures, but the differences between
      AxBFB and ABFB were not significant. CONCLUSIONS: The survival and primary
      patency for the AxBFB group were both inferior to the ABFB group, however a
      multivarate analysis disclosed no significant differences between the two groups.
      Poor femoral run-off and the presence of synchronous infrainguinal reconstructive
      procedures significantly affected graft patency, and these factors modulated the
      patency of AxBFB. AxFB for aortoiliac occlusive disease is therefore considered
      to be an acceptable procedure in appropriately selected patients.

PMID- 11232975
TI  - Preoperative cerebrovascular screening before cardiovascular surgery in a high
      risk area of cerebrovascular events in Japan.
AB  - BACKGROUND: Cerebrovascular disease and cervical artery diseases are potentially
      treatable conditions that are associated with an increased incidence of stroke
      after cardiac surgery. This prospective study was designed to determine the
      prevalence of cerebrovascular diseases in the high risk population of
      cerebrovascular event including some young patients in Japan and establish the
      strategy for cardiac surgery of patients with cerebrovascular disease. METHODS:
      100 (71 male, 29 female) of 126 consecutive patients undergoing cardiac surgery
      under cardiopulmonary bypass were screened for the presence of cerebrovascular
      disease by intra-arterial angiogram. RESULTS: In seven patients angiographic
      evaluation disclosed some evidence of cerebrovascular disease for 50% or greater
      stenosis or cerebral aneurysm. Preoperative 99mTc-Hexamethyl propylene amino
      oxime (99mTc-HMPAO) single emission computed tomography (SPECT) with combination
      of balloon arterial occlusion test provided detailed information of cerebral
      ischemic tolerance and reliable decision making for surgical repair of
      cerebrovascular disease. No deaths were recorded and a small stroke in one
      patient. CONCLUSIONS: We concluded that cerebrovascular screening in patients
      with cardiovascular disease may be requested in a high risk population of
      cerebrovascular events.

PMID- 11232976
TI  - Endovascular repair of abdominal aortic aneurysm in a renal transplant patient.
AB  - A 65-year-old man presented with an asymptomatic infrarenal abdominal aortic
      aneurysm of 6 cm in transverse diameter. Five years before he received a
      cadaveric renal transplant. The patient also had the following risk factors and
      associated diseases: arterial hypertension, coronary artery disease, previous
      myocardial infarction, coronary angioplasty and stent, ileal resection secondary
      to Chron disease, hepatopathy, hyperlipidemia and hepato-renal cystic disease.
      The ASA classification was III, IV. Considering previous abdominal operations and
      risk factors, we decided to repair the aneurysm with a minimal aggression. The
      aneurysm was successfully approached by an endovascular route implanting a 22x10
      bifurcated aorto-iliac endovascular prosthesis. The patient died 13 months later
      after being diagnosed of enterocolitis by cytomegalovirus complicated with sepsis
      and lung infection. We consider this less invasive modality of treatment a valid
      and useful alternative in this high-risk group of patients.

PMID- 11232977
TI  - Surgery for aortoiliac aneurysms in kidney transplant recipients.
AB  - With the increase of long-term survivors following renal transplantation, aorto
      iliac aneurysms requiring surgical management may be encountered more often. Our
      experience with temporary shunts for renal transplant protection during aorto
      iliac aneurysm repair is presented along with a literature review of all cases on
      the subject. Three male patients with a median age of 56 (range 50-61) years were
      operated on for a dissecting aneurysm of the common iliac artery in one,
      respectively abdominal aortic aneurysm in the two remaining patients. All
      patients had impaired transplant function preoperatively with a median serum
      creatinine level of 167 (range 134-202) micromol/L and a median blood urea
      nitrogen concentration of 15 (range 9-23) pmol/L. The intra- and postoperative
      course was uneventful in all patients. Median postoperative serum creatinine
      level and blood urea nitrogen concentration were 135 (range 123-151) micromol/L
      and 10 (range 9-11) pmol/L, respectively. Aorto-iliac surgery in renal transplant
      recipients can be performed without transplant protection. However, in patients
      with a deteriorated transplant function or if a prolonged aortic cross-clamp time
      is anticipated, renal allograft protection measures may be beneficial to prevent
      possible ischemic damage.

PMID- 11232978
TI  - Traumatic scapulothoracic dissociation.
AB  - Scapulothoracic dissociation is an infrequent injury with a potentially
      devastating outcome. The diagnosis is based on clinical and radiographic findings
      of forequarter disruption. These include massive soft tissue swelling of the
      shoulder, displacement of the scapula and neurovascular injuries (brachial
      plexus, subclavian artery and osseous-ligamentous injuries). The mechanism of
      injury appears to be the delivery of severe rotational force sheering the
      shoulder girdle from its chest wall attachments around the scapula, shoulder
      joint and at the clavicle. Early recognition of the entity and aggressive
      treatment are crucial. Outcome is not dependent on management of the arterial
      injury, but rather on the severity of the neurological deficit.

PMID- 11232979
TI  - Management of ipsilateral intrapulmonary metastases in the new TNM system for non
      small cell lung cancer.
AB  - BACKGROUND: Recently, the Union Internationale Contre le Cancer and American
      Joint Committee on Cancer reclassified not only TNM staging but also ipsilateral
      intrapulmonary metastases (PM) as T4 in a same lobe or M1 in different lobes. To
      determine whether the new PM staging is appropriate, we studied the prognosis of
      PM. METHODS: From January 1981 to October 1997, we performed a lobectomy or
      pneumonectomy with mediastinal lymph node dissection, and had 42 patients with
      PM. We analyzed the postoperative prognosis of the patients with ipsilateral PM
      compared with the same stage group without PM (the non-PM). RESULTS: In the
      previous classification of PM (the old PM), 2 patients were categorized as stage
      IIA, 9 as IIB, 17 as IIIA, and 14 as IIIB. After reclassification (the new PM),
      37 patients were categorized as stage IIIB, and 5 as IV. The old PM stage IIIA
      group had a significantly poor prognosis compared with the non-PM stage IIIA.
      However, the prognosis of the new PM group was compatible with that of the non
      PM. None of the other staging group had a significant difference in the
      prognosis. CONCLUSIONS: The management of PM in the new TNM system for non-small
      cell lung cancer is appropriate.

PMID- 11232980
TI  - A randomized trial of postoperative CDDP-based chemotherapy/chemoradiotherapy vs
      short-term immunochemotherapy in lung cancer.
AB  - BACKGROUND: Although a few reports indicated some benefit to survival, the effect
      of adjuvant therapy for the patients with resected lung cancer was still
      controversial. The aim of our study was to evaluate survival advantage of CDDP
      based adjuvant therapy compared with short-term immunochemotherapy. METHODS: 
      EXPERIMENTAL DESIGN: prospective randomized trial. PATIENTS: from 1990 through
      1994, 94 patients were registered. Forty-seven patients were randomly assigned to
      each group, i.e., CDDP-based therapy group (CB Group, CDDP+VDS+tegafur+OK-432 or
      CDDP+OK-432+mediastinal irradiation) or immunochemotherapy group (IC Group,
      tegafur+OK-432). PATIENTS in both groups were followed at 4-month intervals with
      the routine follow-up program of our department. RESULTS: No significant
      difference was observed between the patients' characteristics of two groups.
      Compliance of the regimen in each group was 79% in CB Group and 85% in IC Group.
      No treatment-related death was observed. Five-year survival rates of CB Group and
      IC Group were 49% and 51%, and 5-year disease-free survival rates were 46% and
      44%, respectively. There were no statistical differences between the two groups.
      Furthermore, no survival differences could be found between CB Group and IC Group
      in any subgroup of patients. CONCLUSIONS: Both of these regimens were feasible.
      However, we have not observed any survival benefit in the CB Group in any
      subgroup, so far. Induction therapy, new chemotherapeutic agents, or anti
      angiogenetic a agents may improve the survival of surgically treated lung cancer
      patients.

PMID- 11232981
TI  - Thoracoscopic truncal vagotomy.
AB  - BACKGROUND: Nowadays the only indications to truncal vagotomy is recurrent
      ulceration after previous gastric surgery. Truncal vagotomy allows us to obtain a
      reduction in acid production and to promote ulcer healing, but this technique
      causes pylorospasm in about 20% of cases and this requires further synchronous or
      metachronous pyloric drainage procedure. For this reason, videothoracoscopic
      truncal vagotomy is reserved to patients with gastroresection. METHODS: The
      authors describe 15 patients treated with videothoracoscopic truncal vagotomy. In
      12 patients, a gastrojejunostomy was done according to Roux technique in 2
      patients, a reconstruction according Billroth II technique and in 1 patient, a
      gastroduodenostomy according to Billroth I technique. RESULTS: Videothoracoscopic
      bilateral truncal vagotomy was done in all patients; operation time was 45
      minutes. During the postoperative period there were no complications. No patients
      underwent medical therapy for peptic ulcer. Only in 12 patients was it possible
      to execute an endoscopic follow-up in a period of 3 to 4 years. In all patients
      the ulcer was completely healed. CONCLUSIONS: Complete vagotomy in patients who
      present with recurrent gastrointestinal bleeding after previous gastroresection,
      is associated with significant risks. Videothoracoscopic bilateral truncal
      vagotomy as a simple and efficient procedure seems to be an alternative treatment
      for the management of recurrent ulceration after previous gastric surgery for
      peptic disease.

PMID- 11232982
TI  - Giant tumors of the chest: preoperative embolization and resection.
AB  - Giant tumors of the chest are rare. These tumors comprise a spectrum of disease
      from benign lesions to highly aggressive malignant tumors with cells of origin in
      the pleura, pulmonary parenchyma, blood vessels, thymus, and connective tissues.
      We report four cases of giant tumors of the thorax treated with preoperative
      arterial embolization followed by complete surgical resection. Their diagnostic
      and treatment courses, imaging, and pathology are described.

PMID- 11232983
TI  - Congenital lobar emphysema.
AB  - Congenital lobar emphysema is a cause of respiratory distress during infancy that
      may present a diagnostic problem. Recognition of this entity is rewarding,
      because excisional therapy is fairly specific and the results are satisfactory.
      We present two infants aged 7 weeks and 2 days with congenital lobar emphysema
      who were diagnosed and treated in our institution for the past two years.
      Published work is reviewed; diagnostic and treatment issues are discussed.

PMID- 11232984
TI  - Video-assisted Abruzzini technique for bronchopleural fistula repair. A pathology
      study.
AB  - Trans-sternal closure of the bronchial stump is an effective procedure to treat
      bronchopleural fistula after pneumonectomy. The paper reports a modified video
      assisted Abruzzini technique that, maintaining the same results, should determine
      a lower surgical risk. Three simultaneous approaches are used: cervical video
      mediastinoscopy, right anterior parasternal mediastinotomy, left parasternal
      thoracoscopic access. The dissection of the bronchial stump is performed entirely
      through the mediastinotomy approach after having controlled mediastinal vessels.
      The bronchial stump reamputation is achieved by a roticulator endoGIA introduced
      through the cervicotomy either for the right or left fistulae. The technique
      proposed might reach the same result as the classic approach with lower surgical
      risks.

PMID- 11232985
TI  - Recurrent atrial sarcoma presenting as an atrial myxoma. Long-term survival due
      to surgical intervention and chemotherapy.

PMID- 11232986
TI  - Changes in mortality of acute myocardial infarction as a function of a changing
      treatment during the last two decades.
AB  - Forty years ago, after the establishment of coronary care units, a significant
      decrease in mortality of acute myocardial infarction was noted. Twenty years ago,
      the break-through of thrombolysis realized once again a significant decrease in
      mortality. In this study we compare, in a rather small community hospital, the
      mortality and safety of thrombolytic therapy in acute myocardial infarction with
      a more conventional, conservative medical therapy. We examined all cases of acute
      myocardial infarction between 1978 up to 1998 inclusive, concerning treatment and
      mortality rate after a six month period. To be included in the study, acute
      myocardial infarction had to fulfill particular inclusion criteria. A total of
      1863 cases of acute myocardial infarction were included. The mortality rate of
      patients with acute myocardial infarction treated with thrombolytic agents was
      strikingly lower and statistically very significantly different (p < 0.001) in
      comparison with the mortality rate of patients treated with heparin or coumarine
      derivatives. The mortality rate dropped from 10.57% in the coumarine group and
      from 14.95% in the heparin group to 5.41% in the alteplase group, to 4.95% in the
      anistreplase group and 4.00% in the streptokinase subgroup. The complications
      directly connected to the treatment did not seem to be different between the five
      groups, and they were also not more frequent by using thrombolytic agents. In the
      last 20 years, better preventive measures (life habits, diet, medication) and
      trials to better control the risk factors have not influenced greatly the average
      amount of cholesterol in patients with an acute myocardial infarction. Also the
      percentage of patients with high blood pressure has hardly decreased over the
      last 20 years. The mortality associated with acute myocardial infarction has
      decreased significantly with the use of thrombolytics. In most cases,
      thrombolytics are administered routinely and safely. In this way, they are the
      first choice therapy for myocardial infarction in smaller hospitals. To obtain
      excellent coronary patency, thrombolytic agents with a long half-life and with
      PAI-1 resistance are required in the future. The current measures and medical
      therapies seem to be insufficient to control the risk factors for coronary
      atherosclerosis.

PMID- 11232988
TI  - Is the QT interval an indicator of autonomic state?
AB  - Prolonged QT interval is suggested to indicate an increased risk of sudden
      cardiac death in certain clinical conditions such as diabetes mellitus. We
      investigated whether the individual QT interval is an indicator of an autonomic
      state. An ambulatory 24-hour ECG was recorded in 53 subjects from different
      clinical backgrounds. Power spectral components of heart rate variability (HRV)
      and the QT interval were regressively obtained at a heart rate of 60, 70, 80, 90,
      or 100 beats per minutes (bpm). Log values of the high-frequency component of HRV
      (HF: 0.15-0.50 Hz, a scale of cardiac parasympathetic tone) failed to show a
      relationship with the QT interval. In contrast, the QT interval at a heart rate
      of 90 bpm and 100 bpm showed a significant correlation with the log values of the
      low-frequency component (LF: 0.04-0.15 Hz) and the log[LF/HF], i.e., a putative
      scale of sympathetic tone (100 bpm: QT vs logLF: r = 0.414, p < 0.005, QT vs
      log[LF/HF]: 0.416, p < 0.002). Also, attenuated rate-dependent QT shortening was
      associated with greater logLF and log[LF / HF] values at a heart rate of 80, 90,
      or 100 bpm. These results suggest that the QT interval at a moderate heart rate
      (approximately 90-100 / min) and the degree of rate-dependent QT shortening are
      related to individual sympathetic tone.

PMID- 11232987
TI  - A safe and effective regimen without heparin therapy after successful primary
      coronary stenting in patients with acute myocardial infarction.
AB  - Short-term heparin therapy has been administered routinely after primary coronary
      stenting. However. heparin therapy results in a significantly higher incidence of
      bleeding and vascular complications. A new therapeutic regimen of ticlopidine and
      aspirin without further heparin after coronary stenting in patients without AMI
      has been shown to be safe and reduce the incidence of stent thrombosis. The aim
      of this study was to evaluate whether a new therapeutic regimen of aspirin and
      ticlopidine without heparin is safe and effective in patients with acute
      myocardial infarction (AMI) who have undergone primary coronary stenting and have
      Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow in the infarct-related
      artery. Between January 1997 and September 1999, one hundred and fifty two
      consecutive patients with AMI on Killip score 1 or 2 who underwent primary
      coronary stenting resulting in TIMI grade 3 flow were enrolled and divided into
      two groups: Group 1 (n = 95 patients) received aspirin, ticlopidine and further
      intravenous heparin infusion for 48 hours following primary coronary stenting;
      Group 2 (n = 57 patients) received only aspirin and ticlopidine without further
      heparin therapy following primary coronary stenting. No in-hospital major cardiac
      events were observed in either group. However, the combined incidence of bleeding
      and vascular complications (27.4% vs 12.3%, p = 0.029) and the need for blood
      transfusions (9.5% vs 0%, p = 0.013) were significantly higher in Group I
      patients. Furthermore, hospital stay was also longer in Group I patients (5.8+/
      2.4 vs 4.7+/-1.7 days, p = 0.0003). At the 30-day follow-up, there were no
      differences (1.05% vs 0%, p = 0.63) in the combined incidence of vascular
      complications and the major cardiac events were similar (1.05% vs 1.75%, p =
      0.71) between the groups. The results suggest that further heparin therapy
      following primary coronary stenting increases the combined incidence of bleeding
      and vascular complications as well as the need for blood transfusions and
      prolongs the length of hospital stay without further benefit to those patients
      with coronary flow restored to TIMI 3 grade flow.

PMID- 11232989
TI  - Left atrial systolic function assessed by left atrial ejection force in patients
      with sick sinus syndrome and paroxysmal atrial fibrillation.
AB  - We evaluated left atrial systolic function using left atrial ejection force
      (LAEF) in 19 patients with sick sinus syndrome (SSS) and in 20 with paroxysmal
      atrial fibrillation (Paf) whose ages ranged from 48 to 80 years. We also
      evaluated 35 normal individuals for comparison. The LAEF was calculated as 1/3 x
      mitral valve area x (peak velocity of A wave)2 using two-dimensional and pulsed
      Doppler echocardiography according to Newton's law of motion and hydrodynamics.
      In normal individuals, LAEF positively correlated with age (r = 0.82, p < 0.01).
      Normal LAEF was calculated as 0.098 x age - 0.74 (kdynes) from the regression
      line. Because of this correlation, we used age-corrected LAEF (%LAEF) that was
      calculated as (measured LAEF / normal LAEF) x 100. The results showed that this
      value was 53+/-26% in patients with SSS and 54+/-26% in patients with Paf. Both
      were significantly lower than normal individuals (p < 0.001). Among SSS subtypes,
      %LAEF was lower in types II and III than in type I (51+/-14%, 37+/-19%, and 81+/
      35%, respectively). In conclusion, left atrial systolic function is depressed in
      patients with Paf and SSS, in particular, types II and III. These results suggest
      that the pathological abnormalities extend not only to the sinus node but also to
      the left atrial muscle in patients with SSS and Paf.

PMID- 11232990
TI  - Apoptotic cell death in arrhythmogenic right ventricular cardiomyopathy: a
      comparative study with idiopathic sustained ventricular tachycardia.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a specific heart muscle
      disease of unknown etiology characterized by fatty and fibrofatty replacement of
      the right ventricular myocardium. It often manifests life-threatened ventricular
      arrhythmias. Previous studies have hypothesized that myocyte apoptosis
      contributes to the myocyte cell loss and fatty change in ARVC and may be induced
      by recurrent ventricular tachycardia (VT). We examined whether these progressive
      pathological changes result from apoptotic cell death in both autopsied and
      biopsied right ventricular myocardium from 35 patients with ARVC by using in situ
      terminal deoxynucleotidyl transferase assay (TUNEL) and agarose gel
      electrophoresis. We also studied the biopsied myocardium from 30 patients with
      idiopathic sustained VT whose origin was the outflow tract of the right
      ventricle. TUNEL-positive cells indicating DNA fragments were observed in some
      cardiomyocytes and fibroblasts in ARVC, but the numbers of TUNEL-positive
      myocytes were very low in idiopathic VT. DNA laddering was confirmed in two
      autopsied cases in ARVC, but not in a non-cardiac case who died. These results
      suggest that at least some cardiomyocytes and fibroblasts are subjected to
      apoptosis in ARVC, leading to the loss of myocardium with characteristic
      pathological changes and subsequently progressive cardiomyopathy. Furthermore,
      the apoptotic process may not result from myocardial ischemia due to repetitive
      VT.

PMID- 11232992
TI  - Sclerosant therapy for delayed cardiac tampo-nade after coronary artery bypass
      grafting.
AB  - A 56-year-old Japanese male with delayed cardiac tamponade which occurred 13
      months after coronary artery bypass grafting (CABG) is presented. The patient was
      admitted to our hospital suffering from dypnea due to cardiac tamponade.
      Pericardiocentesis yielded a viscous bloody fluid. The patient recovered after
      continuous drainage followed by an intra-pericardial administration of
      minocycline hydrochloride. Sclerosant therapy is considered to be a treatment of
      choice for delayed cardiac tamponade following CABG.

PMID- 11232991
TI  - Endothelium-dependent coronary response is impaired in the myocardium at an early
      phase of post-infarct remodeling.
AB  - The aim of the present study was to characterize endothelium-dependent and 
      independent coronary functions in remodeling hearts after infarction. First,
      echocardiography showed that the left ventricular diastolic dimension and
      thickness of the non-ischemic region were increased by 25% and 20%, respectively,
      at 2 weeks after coronary ligation in the rabbit heart. In the second series of
      experiments, 2 weeks after coronary ligation or a sham operation, the heart was
      isolated and perfused with modified Krebs-Henseleit buffer at 75 mmHg, and
      effluent from the pulmonary artery was measured as total coronary flow (CF).
      Regional CF analysis by microspheres indicated that flow to the infarcted region
      as a percentage of total CF is negligibly small. There was no significant
      difference between CF responses to sodium nitroprusside (10(-9)-10(-5) mole/l) in
      the sham-operated and remodeling hearts. However, the increase in CF after
      acetylcholine (ACh: 10(-8)-10(-5) mole/l) injection was significantly reduced by
      approximately 50% in the remodeling hearts compared to that in the sham-operated
      hearts. Furthermore, the percent increase in CF by ACh (10(-5) mole/l) was
      inversely correlated with weight of the remodeling myocardium (r = -0.630, p <
      0.05). These results suggest that endothelium-dependent vasodilatory function is
      impaired in the myocardium at the early stage of post-infarct remodeling and that
      this endothelial dysfunction is closely related to the degree of hypertrophy of
      the remodeling myocardium.

PMID- 11232993
TI  - A case of acute myocardial infarction: intracoronary thrombus formation at a
      previously provoked vasospasm site.
AB  - A 58-year-old Japanese man with variant angina developed acute myocardial
      infarction (AMI). Emergency coronary angiography demonstrated thrombotic
      occlusion in the proximal site of the left anterior descending artery. The
      occluded region appeared to be coincident with the area in which severe vasospasm
      had been provoked by intracoronary administration of acetylcholine 1.5 years
      before the onset of AMI. This case may give us a unique opportunity to consider
      the role of vasospasm in the etiology of AMI.

PMID- 11232994
TI  - Overdrive suppression of antegrade conduction over the accessory pathway.
AB  - In a patient with Wolff-Parkinson-White syndrome whose accessory pathway was
      primarily capable of bidirectional conduction, antegrade conduction over the
      accessory pathway was transiently inhibited after rapid atrial or ventricular
      pacing or after spontaneous termination of atrioventricular reentrant
      tachycardia. Pacing rate and duration of tachycardia were related to the duration
      of the suppression of preexcitation, while the coupling interval of the first
      sinus beat to the last driven or tachycardia beat was irrelevant to the
      phenomenon. Thus, overdrive suppression of conduction may be the most likely
      mechanism of this phenomenon.

PMID- 11232995
TI  - Ventricular septal defect and left ventricular aneurysm: late occurrence as
      complications of an acute myocardial infarction.
AB  - Mechanical complications of acute myocardial infarction (AMI) such as a
      ventricular septal defect (VSD) usually occur within the first week. In the
      thrombolytic era, the incidence of a VSD has not increased, but has been reported
      to occur earlier than previously described. We report an unusual case of an
      elderly Caucasian female with an acute anterior wall myocardial infarction
      treated with thrombolytic therapy. Her AMI was complicated by pulmonary edema
      secondary to a VSD and a left ventricular aneurysm five weeks later. Prompt
      diagnosis, immediate surgical closure of the VSD, and aneurysmectomy resulted in
      her complete recovery.

PMID- 11232996
TI  - A case of penetrating aortic atherosclerotic ulcer with hemoptysis.
AB  - A 69-year old Japanese woman with hypertension was admitted because of continuous
      back pain and recurrent hemoptysis. Radiographic findings showed an enhanced
      irregular mass, at the aortic arch fed by the tracheal artery, which implied both
      a penetrating aortic atherosclerotic ulcer and lung cancer. Diagnostic surgery
      revealed no evidence of cancer but did reveal a rupture of the intima at the
      distal part of the aortic arch. It is assumed that the transmural oozing occurred
      after development of the penetrating aortic ulcer, which formed an extra-aortic
      hematoma and caused surrounding inflammation, and led to tracheal artery feeding.
      The intramural hematoma might have weakened vascular wall tension from the aorta,
      and formed an oozing extra-aortic hematoma instead of an acute rupture.

PMID- 11232997
TI  - Delayed onset of amaurosis fugax in a patient with type A aortic dissection post
      surgical repair.
AB  - Stroke is an important complication for the surgical treatment of type A aortic
      dissection and it occurs immediately post operation. Many surgical techniques
      such as deep hypothermic circulatory arrest and retrograde cerebral perfusion
      have been reported to ameliorate this complication. We report here a male
      Taiwanese patient with type A aortic dissection involving the arch who underwent
      surgical repair. Amaurosis fugax appeared on the 4th day post operation.
      Funduscopic findings demonstrated multi focal embolization and carotid sonography
      revealed normal carotid arteries. The symptoms and signs improved after
      anticoagulation therapy. This is a rare case of delayed onset of amaurosis fugax
      in a patient with type A aortic dissection post surgical repair. The
      thromboemboli might have originated from the internal surface of the sawing area.

PMID- 11232998
TI  - Bayesian segregation analysis of production traits in two strains of laying
      chickens.
AB  - A bayesian marker-free segregation analysis was applied to search for evidence of
      segregating genes affecting production traits in two strains of laying hens under
      long-term selection. The study used data from 6 generations of Leghorn (H77) and
      New Hampshire (N88) breeding nuclei. Estimation of marginal posterior means of
      variance components and parameters of a single autosomal locus was performed by
      use of the Gibbs sampler. The results showed evidence for a mixed major gene: 
      polygenic inheritance of BW and age at sexual maturity (ASM) in both strains.
      Single genes affecting BW and ASM explained one-third of the genetic variance.
      For ASM large overdominance effect at single locus was estimated. Initial egg
      production (IEP) and average egg weight (EW) showed a polygenic model of
      inheritance. The polygenic heritability estimates for BW, ASM, IEP, and EW were
      0.32, 0.25, 0.23, and 0.08 in Strain H77 and 0.25, 0.24, 0.11, and 0.38 in Strain
      N88, respectively.

PMID- 11232999
TI  - Examining the effects of prestorage incubation of turkey breeder eggs on
      embryonic development and hatchability of eggs stored for four or fourteen days.
AB  - Thirty-six hundred British United Turkey hatching eggs were used in two separate
      trials to test whether prestorage incubation (PRESI) treatments of 0, 6, and 12 h
      (Trial 1) or 0, 7, and 14 h (Trial 2) could improve the hatchability of eggs
      stored (17 C) for 14 versus 4 d. The development of the embryos (n = 30) was
      staged before and after exposing eggs to the various PRESI treatments. Embryonic
      development was also established after storage to ascertain whether embryonic
      development was occurring during storage. The remaining eggs in each trial were
      split into three groups (n = 500) and incubated for 28 d to examine embryonic
      mortality and hatchability. No changes were observed in embryonic development due
      to egg storage. Embryos were significantly more developed as the number of PRESI
      h increased; therefore, embryos from different PRESI treatments were placed in
      storage at different stages of development. Early mortality (1 to 7 d of
      incubation), mortality at internal and external pipping, and hatchability of
      fertile eggs were significantly reduced in eggs stored for 14 versus 4 d. The
      various PRESI treatments did not significantly affect the mortality or
      hatchability of eggs stored for 4 d. However, the hatchability of eggs incubated
      prior to storage for 12 h and then stored for 14 d was restored to the levels
      reported for eggs subjected to the treatment that represents the industry norm (0
      h of PRESI and 4 d storage). These results indicate that embryos of eggs stored
      for 14 d, which have developmentally advanced to the stage of complete hypoblast
      formation (PRESI for 12 h), have a survival advantage over eggs stored for 14 d
      that have not been subjected to any PRESI.

PMID- 11233000
TI  - Evaluation of the efficacy of bentonite from the south of Argentina to ameliorate
      the toxic effects of aflatoxin in broilers.
AB  - In vitro studies indicated that a sodium bentonite (SB) from southern Argentina
      had a high ability to sorb aflatoxin B1 (AFB1) from aqueous solution. We
      evaluated this compound for its ability to reduce the effects of total aflatoxins
      (AF; 5 mg AFB1/kg) in the diet of growing broiler chickens from 30 to 52 d of
      age. The diets were amended with 0.3% Argentinean SB to determine the effect of
      this compound during aflatoxicosis. When compared with the controls, BW gains
      were significantly (P < 0.05) lower for broilers fed diets containing AF alone
      (1,865 vs. 1,552 g). No differences were found between the BW gains of broiler
      chickens fed diets without AF (1,785 g) and those of chickens fed AF + SB (1,809
      g). These results suggest that effects of AF treatment were ameliorated when SB
      was used in the broiler chick diets. The AF significantly (P < 0.05) decreased
      feed efficiency. Liver, kidney, and pancreas relative weights increased in
      chickens fed the diet containing AF alone. Alterations in the levels of serum
      total protein, albumin (ALB), and globulins (GLOB) were observed for AF diets,
      and moderate protection was provided by the sorbent. The ALB:GLOB ratio decreased
      in both groups of birds fed with the AF-contaminated diet, and we observed a
      moderate increase in this ratio by 0.3% addition of SB. The histopathological
      findings in liver sections of broiler fed diets with AF + SB indicated a
      nonprotective effect of this adsorbent, because a moderate hepatic steatosis was
      observed.

PMID- 11233001
TI  - Systemic distribution of Staphylococcus aureus following intradermal footpad
      challenge of broilers.
AB  - We conducted an experiment with broilers to determine if prior exposure to
      Staphylococcus aureus would facilitate the systemic infiltration of this pathogen
      following intradermal footpad challenge with live S. aureus. Litter-raised
      broilers were sensitized at 3 and 4 wk of age with s.c. injections in the neck
      with heat-killed S. aureus diluted in polyethylene glycol (PEG). Equal numbers of
      control birds were injected at the same times with PEG. At 7 wk of age, chicks
      previously sensitized to killed S. aureus or injected with PEG were injected
      intradermally in the right footpad with PBS or live S. aureus. The left footpads
      of all birds were injected with PBS. The difference in thickness between the
      right and left footpads was determined at 0, 24, and 48 h postchallenge. Blood,
      liver, spleen, lung, and synovial fluid were collected six times between 1 and 48
      h postchallenge to determine the recovery of S. aureus. Sensitized and non
      sensitized birds showed footpad swelling following challenge with live S. aureus
      in the right footpad (P < 0.001). Injection of PBS did not induce footpad
      swelling. Birds injected in the footpads with live S. aureus as compared to PBS
      had significantly higher isolation rates of S. aureus in the spleen, liver, and
      blood; however, recovery of S. aureus from S. aureus-sensitized and PEG-injected
      birds was not significantly different. Time postchallenge (1, 3, 7, 11, 24, and
      48 h) had no significant effect on the recovery of S. aureus. It was concluded
      that the intradermal challenge of the footpad with S. aureus resulted in systemic
      infiltration of S. aureus into the spleen, liver, and blood. Prior exposures to
      killed S. aureus as compared to PEG controls did not affect the systemic
      distribution of S.

PMID- 11233002
TI  - Prevalence of Campylobacter and Salmonella at a squab (young pigeon) processing
      plant.
AB  - Microbiological testing for Campylobacter and Salmonella was performed at a
      processing plant for squab (young pigeon) in three separate trials. Live birds,
      carcasses, and equipment were targeted for sampling during the preslaughter, pre
      evisceration, and postevisceration stages of processing. The three trials
      represented 18 farms (1,110 squab), 1 farm (250 squab), and 23 farms (2,900
      squab). The overall prevalence of positive samples in Trial 1 was 1.4% for
      Salmonella spp. and 11.1% for C. jejuni; in Trial 2, 4.3 and 0% for Salmonella
      spp. and C. jejuni; and in Trial 3, 4.1 and 4.8% for Salmonella spp. and C.
      jejuni, respectively. These observations represent a significantly greater
      likelihood of having a positive sample for Campylobacter (twofold) or Salmonella
      (eightfold) at processing, compared with prevalences observed in our previous on
      farm study. This finding suggests an overall increase in the number of carcasses
      contaminated or in the concentration of contamination during transport and
      processing. In the multifarm trials, only Trial 3 demonstrated a significant
      increase in the prevalence of positive samples from the preslaughter to the
      postevisceration stages of processing (P = 0.02), and only for Campylobacter. The
      prevalence of positive cultures from equipment surfaces were not different than
      carcasses during processing, therefore no additional critical control points were
      identified within this system. When pooled swabs were compared (Trial 1) to
      individual swabs (Trials 2 and 3), no statistical difference in the prevalence of
      Salmonella or Campylobacter was observed between trials. Direct plating from a
      pooled sample onto selective agar media (Trial 1) and single swab culture with
      enrichment followed by plating on selective agar (Trials 2 and 3) were compared
      for Campylobacter isolation. No statistical difference in C. jejuni prevalence
      was observed using either method; however, when the detection limit of each
      method was determined, single swabs with enrichment had greater sensitivity.

PMID- 11233003
TI  - Comparison of mucosal competitive exclusion and competitive exclusion treatment
      to reduce Salmonella and Campylobacter spp. colonization in broiler chickens.
AB  - Control of Salmonella spp. during the earliest phases of broiler production may
      provide the best opportunity to reduce human pathogens on processed broiler
      carcasses. Application of the "Nurmi concept" has been demonstrated to be an
      effective means in reducing Salmonella colonization among broiler chicks. In
      1989, Aho et al. developed a competitive exclusion (CE) culture for control of
      Salmonella spp., whereas a mucosal competitive exclusion culture (MCE) developed
      in the United States was originally created to control Campylobacter colonization
      (Stern et al., 1995). The major differences in the two patents were the higher
      level of anaerobic culture required, the degree of epithelial scraping and
      washing of the ceca, media used for subculturing, and the culture incubation
      temperatures (35 C vs. 42 C). The CE and MCE were compared for efficacy in
      reducing Salmonella and Campylobacter colonization in broiler chicks. Nine adult
      birds (three for each of three replicates) were slaughtered, and each of a bird's
      paired ceca were used to produce corresponding antagonistic microflora, which
      were administered to day-of-hatch chicks. The chicks (a total of 210) were
      challenged 24 h later with Salmonella and Campylobacter and were killed 1 wk
      later, and levels of the pathogens were determined. Ninety CE-treated birds were
      significantly more colonized by Salmonella typhimurium than those 90 chicks
      treated with the MCE microflora (3.97 log 10 cfu/g cecal contents vs. 1.25 log 10
      cfu/g cecal contents). Also, Campylobacter spp. colonization of these birds was
      significantly higher for CE-treated birds when compared with MCE-treated birds
      (6.96 log 10 cfu/g cecal contents vs. 5.03 log 10 cfu/g cecal contents). These
      results can be useful in developing intervention strategies to reduce chicken
      colonization by Salmonella and Campylobacter.

PMID- 11233004
TI  - Expression of protein tyrosine kinases and stem cell factor in chicken
      blastodermal cells.
AB  - Chicken blastodermal cells (CBC) from Stage X embryos, which were isolated from
      newly laid, fertile, unincubated eggs, are pluripotent cells and can produce
      somatic and germline chimeras when injected into recipient stage X embryos. The
      CBC retain their pluripotential ability for up to 7 d in vitro. The molecular
      mechanisms that control proliferation and differentiation of CBC are largely
      unknown, although protein tyrosine kinases (PTK) are known to play important
      roles in these processes in similar cells. To understand better the molecular
      mechanisms of proliferation and differentiation in CBC, expression profiles of
      PTK and stem cell factor (SCF) were analyzed by reverse transcription polymerase
      chain reaction (RT-PCR) using gene-specific and degenerate oligonucleotide
      primers. Seventeen distinct PTK, including 14 receptor-type and 3 nonreceptor
      type PTK and SCF were identified by RT-PCR. Expression of all of the genes was
      confirmed by northern blot analysis. The northern blot analysis showed that all
      probes hybridized with one or more transcripts at various expression levels. The
      expression of the 17 PTK and SCF genes in CBC suggests that they might play a
      role in signal transduction pathways that control the proliferation or
      differentiation in CBC.

PMID- 11233005
TI  - Avian T helper one/two immune response balance can be shifted toward inflammation
      by antigen delivery to scavenger receptors.
AB  - Whether immune responses are dominated by inflammation or antibody production is
      often key to surviving infections. Therefore, differential control of these
      immune pathways determined by CD4 T cells is of fundamental interest for vaccine
      design. Little is known about how inflammatory [T helper cell (Th) type 1 (Th1)]
      versus antibody-inducing (Th2) choices are controlled in domestic fowl. To
      address this, MHC-matched chickens were immunized to test whether antibody
      dominated Th2 or inflammatory Th1 responses could be preferentially activated,
      and our findings subsequently extended to outbred broiler breeders. Strategies
      used were known to shift the response in mice from Th2 to Th1 by delivering the
      injected antigen preferentially to macrophages. The model antigen, BSA, was
      maleylated to allow binding to scavenger receptors (SR) present on mammalian
      macrophages. Maleyl-BSA bound well in receptor-specific fashion to a chicken
      macrophage cell line. Compared with native BSA, immunization with SR-binding,
      maleyl-BSA modulated the immune response toward the Th1 pathway, as evident by
      increases in the magnitude of in vivo inflammatory reactions and declines in
      antibody-making responses. Initiation of a maleyl-BSA Th1 pathway is further
      supported by the enhanced ability of splenocytes to express mRNA for interferon
      gamma in response to antigens. Together, these data establish the presence and
      functional relevance of SR in domestic fowl as well as provide a system for
      investigating the mechanisms controlling Th1/Th2 pathways in chickens. Moreover,
      the ability to direct immune responses toward either pathway by antigen
      maleylation will contribute significantly to the development of better vaccines
      for poultry diseases.

PMID- 11233006
TI  - Development of procedures for determining the amino acid requirements of chickens
      by the indicator amino acid oxidation method.
AB  - To better understand the amino acid requirements of chickens, a method is needed
      to determine a point estimate of the requirement. A method developed to determine
      the amino acid requirements of piglets and human infants by using the oxidation
      rate of an indicator amino acid as the test parameter was adapted for use in
      growing chickens. Polycarbonate chambers measuring 30 x 40 x 30 (L x W x H) were
      constructed to house one small mature chicken or several small immature chickens
      and to trap exhaled CO2. In the first experiment, 10-d-old chicks (250 to 300 g
      each) were feed deprived for 12 h and given 1 g of a methionine-deficient diet
      (gavage) with L-[1-C14]phenylalanine. Peak oxidation of L-[1-C14]phenylalanine
      occurred between 30 and 90 min (-200 dpm/g). A linear rate of oxidation (slope = 
      1.84; r2 = 0.96) was achieved by 120 min after feeding until after 180 min, when
      oxidation stabilized at a low rate. The second experiment tested different
      chambers and chicks with the same treatment to show repeatability. There were
      four chicks (250 to 300 g each) in each of three apparently identical chambers.
      Chicks were given two meals labeled with L-[1-C14]phenylalanine, 2 h apart. The
      CV for the 0- and 30-min collections were 17 and 10%, respectively. The CV for
      the remaining collections remained at <4%. These data supported a system of two
      feedings, 2 h apart to reduce variability and a collection period that included
      up to 3 h after the second feeding.

PMID- 11233008
TI  - Effects of feeding locally grown whole barley with or without enzyme addition and
      whole wheat on broiler performance and carcass traits.
AB  - Two experiments were conducted to investigate the impact of increasing dietary
      levels of whole barley (WB) with or without exogenous enzymes and of whole wheat
      (WW) without E fed from 7 d of age, on performance and carcass characteristics of
      broilers. Experiment 1 was conducted with corn-soybean meal grower diets
      containing WB at 0, 10, 10 + enzymes, 15, or 15% + enzymes. The finisher diets
      contained, as fed, WB at 0, 15, 20 + enzymes, 15, or 20% + enzymes. In Experiment
      2, grower diets contained 0, 10, 10, 20, or 20% WW with 0, 20, 35, 20, or 35% WW
      in the finisher diets. No enzymes were used for WW diets. In each Experiment,
      1,500 1-d-old Ross x Ross male broilers were randomly distributed in 30 floor
      pens of 50 birds each. Six replicates were allotted to each treatment. Body
      weight, average daily gain (ADG), feed intake (FI), and feed efficiency ratio
      (FER) were measured at 7, 21, and at 38 d of age. In Experiment 1, ADG was lower
      (P < 0.05) in the control vs. Diet 5. However, FER with enzyme addition was
      lower, and FI with enzymes was higher (P < 0.05). Final BW, gizzard, and pancreas
      weights were higher (P < 0.05) with WB inclusion. In Experiment 2, ADG and BW
      significantly increased with addition of WW, although the response was best for
      Diets 2 and 3. Abdominal fat and carcass weights increased (P < 0.05) with the WW
      levels in the diets.

PMID- 11233007
TI  - Influence of two dietary fats on the composition of emu oil and meat.
AB  - Male and female emus were fed a diet rich in saturated fat (beef tallow) or a
      diet rich in unsaturated fat (soybean oil) until they weighed about 35 kg.
      Samples of subcutaneous and retroperitoneal adipose tissues and samples of six
      major meat cuts were taken for determination of composition. Emus fed the two
      different diets grew at similar rates, but the male emus had a higher percentage
      of carcass fat. The adipose tissue cells from males were larger than those from
      females. All six meat cuts averaged 2.2% fat, with the regular filet having the
      most and the inside and outside drums the least. Cholesterol concentration of all
      sizes of meat cuts averaged 32.2 mg/100 g meat. Diet did not influence
      cholesterol content of the rendered oil. Fan filets had the greatest
      concentration of cholesterol, and the inside and outside drums had the least.
      Source of dietary fat had no effect on fat and cholesterol content of the meats.
      Meat from emus fed beef tallow was more tender and juicy. Fan filets were the
      most tender meat, had the least intense flavor, and were the most flavorful.
      Untrained panelists were able to discriminate between emu meat and beef. Source
      of dietary fat did not influence the fatty acid compositions of the meats. As
      expected, the soybean oil-fed emus produced oil that was more polyunsaturated
      than did the tallow-fed emus.

PMID- 11233009
TI  - Performance of broilers and production and egg quality parameters of laying hens
      fed 60% raw or treated common vetch (Vicia sativa) seeds.
AB  - Two experiments were conducted to study the effect of feeding 60% untreated (U)
      or coarsely ground treated vetch (V) seeds on performance of broilers and laying
      hens. In Experiment 1, the V seeds were soaked in 1% NaHCO3 (1:10) or in 1%
      acetic acid (1:5) at room temperature for 24 h (RTAA). Birds on the NaHCO3
      treated V diet had 100% mortality rate but had significantly longer survival time
      than those on UV (14.9 vs 5.1 d). Birds on RTAA-V survived and had similar BW and
      feed conversion but greater kidney size than those of the controls at 7 wk of age
      (P < 0.05). In Experiment 2, control, UV, V soaked in water at 40 C (40WV), RTAA
      V, and V soaked in acetic acid at 40 C (40AAV) diets were fed to laying hens for
      84 d. The ground seeds in RTAA-V and 40AAV were soaked in acetic acid (1:10) at
      room temperature or at 40 C, respectively, for 24 h. For 40WV, the seeds were
      soaked in water (1:10) at 40 C for 72 h with a water change every 12 h. The UV
      fed hens ceased egg production within 14 d and had the highest BW loss and the
      lowest feed intake among all treatments (P < 0.05). The 40WV and 40AAV
      significantly improved these criteria. Moreover, the RTAA-V resulted in
      performance comparable to that of the controls. Eggs produced by hens on treated
      V diets had similar weight but higher Haugh unit score (11 points), thinner
      shell, and lower yolk color score than those of the controls (P < 0.05). Results
      indicated that RTAA-V at 60% dietary level was not detrimental to broilers and
      laying hens.

PMID- 11233010
TI  - Metabolizable energy value of conjugated linoleic acid for broiler chicks and
      laying hens.
AB  - Two experiments with broiler chicks and one experiment with laying hens were
      conducted to determine the MEn value of conjugated linoleic acid (CLA). In
      Experiment 1, for 8 d, 16-d-old chicks were fed diets in which 4, 8, or 12% of
      CLA Source A or 4, 8, or 12% of soybean oil (SO) was substituted for glucose.
      Dietary MEn increased linearly (P < or = 0.001) with increments of CLA Source A
      or SO. Regression analysis relating increases in dietary MEn and increments of
      the dietary fat sources showed that the MEn values of CLA Source A and SO, when
      evaluated separately, were 7,419 and 8,429 kcal/kg, respectively. In Experiment
      2, feed was withheld from laying hens for 38 h and then the hens were force-fed
      diets containing 15% glucose, 15% CLA Source A, or 15% SO (two feedings of 30 g
      each). Excreta samples were collected for 36 h after the last feeding. The MEn
      values obtained for CLA Source A and SO were 8,517 and 8,437 kcal/kg,
      respectively. The MEn of CLA Source B (higher in unsaturated fatty acids than CLA
      Source A) was determined in Experiment 3 by feeding diets containing 4, 8, or 12%
      CLA Source B to 14-d-old chicks. Increases in dietary MEn with increments of CLA
      Source B were curvilinear, with resulting MEn of 9,375 to 9,588 kcal/kg of fat
      when CLA Source B was fed at 4 or 8% of the diet and 7,917 kcal/kg when fed at
      12% of the diet. Results of this research show that CLA sources can contribute
      substantial energy to diets, but the MEn value of CLA sources for young chicks
      varies with fatty acid composition and dietary concentration.

PMID- 11233011
TI  - Evaluation of valine requirement of the commercial layer using a corn-soybean
      meal basal diet.
AB  - An experiment was conducted with Hy-Line W-36 hens to evaluate the Val
      requirement in a corn-soybean meal diet. Eight experimental diets were fed with
      Val levels of 0.700, 0.665, 0.630, 0.595, 0.560, and 0.525%. A positive control
      (0.765% Val) was fed. Egg production (EP) was increased by addition of Val to
      0.630%. Egg weight (EW) was increased by addition of Val to 0.655%. Broken-line
      regression indicated a daily Val requirement of 592.5, 677.7, and 619.0 mg/hen
      per d for EP, EW, and egg contents (EC), respectively. This requirement was 13.1
      mg/g of EC.

PMID- 11233012
TI  - Artificial incubation of Muscovy duck eggs: why some eggs hatch and others do
      not.
AB  - This study was designed to gain insight into the influence of spraying and
      cooling, during artificial incubation, on the embryo metabolic rate and hatching
      ability of Muscovy duck eggs. Three times a week 93 incubated eggs were sprayed
      and cooled for 0.5 h at room temperature. Daily embryo metabolic rate was
      measured in 30 eggs with a water vapor conductance ranging from 1.15 to 2.07
      mg/day-kPa. Egg weight ranged from 63.73 to 84.52 g; length and breadth ranged
      from 59.6 to 66.4 mm and 43.2 to 48.2 mm, respectively. According to observed
      hatching ability, eggs were classified by three categories: eggs that hatched
      normally; eggs that were assisted during hatching, and nonhatched eggs. Five
      ducklings were assisted during hatching. Four ducklings died on Day 31, two on
      Day 32, and two on Day 34. Two functions were derived by discriminant analysis
      and accounted for 100% of the variation among the three categories of hatching
      ability. Collectively, these functions were able to classify 93.3% of the eggs in
      the correct hatching category. Egg length and metabolic rate at Days 21 and 28 of
      incubation were the most important predictor variables of the two functions. The
      results obtained in the present study indicate that an incubation temperature of
      37.5 C with spraying and cooling seems to be beneficial for larger eggs.

PMID- 11233013
TI  - Plasma concentrations of 13,14-dihydro-15-keto PGF2alpha and progesterone during
      the oviposition cycle of the domestic goose (Anser anser domesticus).
AB  - Plasma 13,14-dihydro-15-keto prostaglandin F2alpha (PGFM) and progesterone levels
      were determined in actively ovulating, 1- to 2-yr-old female geese (Anser anser
      domesticus) at hourly intervals during the oviposition cycle, using the enzyme
      immunoassay (EIA) technique. The plasma PGFM concentration showed a peak at the
      time of oviposition and decreased to a basal level after oviposition.
      Progesterone levels began to surge approximately 12 to 13 h before ovulation and
      reached a peak 2 to 3 h before ovulation. The plasma progesterone concentrations
      returned to basal level at the time of ovulation. The present method of EIA was
      found to have practical application in analyses of progesterone and PGFM in
      plasma of birds.

PMID- 11233014
TI  - Dietary palm oil alters the lipid stability of polyunsaturated fatty acid
      modified poultry products.
AB  - Laying hens were fed a high polyunsaturated fatty acid (PUFA) diet with three
      levels [low (LPO, 0%), medium (MPO, 1.5%), and high (HPO, 3.5%)] of palm oil (PO)
      or a PUFA diet with tocopherol mix (control). Flax and fish oils were used as
      PUFA sources in all of the diets. Inclusion of tocopherols resulted in a lower (P
      < 0.05) thiobarbituric acid reactive substances (TBARS) in the control eggs in
      white and dark meats. Among the PO treatments, eggs from HPO diet had the lowest
      TBARS (P < 0.05). A higher (P < 0.05) TBARS was observed for eggs, meat, and
      liver from hens on the LPO diet. No difference was observed between the TBARS of
      LPO and MPO dark meat. The C22:6 n-3 fatty acid was lower (P < 0.05) in MPO and
      HPO eggs and the HPO white meat.

PMID- 11233015
TI  - Volatile profiles and lipid oxidation of irradiated cooked chicken meat from
      laying hens fed diets containing conjugated linoleic acid.
AB  - The objective of this study was to determine the influence of dietary conjugated
      linoleic acid (CLA) on lipid oxidation, volatile profiles, and sensory
      characteristics of irradiated cooked chicken meat. Forty-eight 27-wk-old White
      Leghorn hens were fed a diet containing 0, 1.25, 2.5, or 5.0% CLA. After 12 wk of
      feeding trial, hens were slaughtered, and boneless, skinless breast and thigh
      muscles were separated. Meats of three birds from a dietary treatment were pooled
      and ground together through a 9-mm and a 3-mm plate, and patties were prepared.
      Patties were individually packaged and cooked in a water bath at 85 C for 15 min.
      After cooling to room temperature, patties were repackaged in oxygen-permeable or
      oxygen-impermeable bags, irradiated at 0 or 3 kiloGray (kGy) with an electron
      beam irradiator, and analyzed for lipid oxidation, volatile profiles, and sensory
      characteristics at 0 and 5 d of storage at 4 C. Cooked meat patties from hens fed
      CLA diets had lower TBA-reactive substances values and produced less hexanal and
      pentanal than the control. The irradiated and nonirradiated cooked chicken meat
      with aerobic packaging developed severe lipid oxidation during the 5-d storage at
      4 C. Irradiation accelerated lipid oxidation in aerobic-packaged cooked chicken
      meat, but its effect was not as significant as that of the packaging. No odor
      differences were found among the cooked chicken meats from the different dietary
      CLA treatments. The increased storage stability of cooked meat from hens fed CLA
      diets was caused by the increased saturated fatty acids and CLA content in meat
      lipids. Tissue CLA was stable from oxidative changes and had minimal effect on
      volatile production in irradiated and nonirradiated cooked chicken meat during
      storage.

PMID- 11233016
TI  - Invited review: the scientific basis of Lactobacillus acidophilus NCFM
      functionality as a probiotic.
AB  - Lactobacillus acidophilus NCFM is a probiotic strain available in conventional
      foods (milk, yogurt, and toddler formula) and dietary supplements. Its commercial
      availability in the United States since the mid-1970s is predicated on its
      safety, its amenability to commercial manipulation, and its biochemical and
      physiological attributes presumed to be important to human probiotic
      functionality. The strain has been characterized in vitro, in animal studies, and
      in humans. NCFM is the progenitor of the strain being used for complete
      chromosome sequencing and therefore will be a cornerstone strain for
      understanding the relationship between genetics and probiotic functionality. Both
      phenotypic and genotypic techniques have verified its taxonomic status as a type
      A1 L. acidophilus strain. It adheres to Caco-2 and mucus-secreting HT-29 cell
      culture systems, produces antimicrobial compounds, and is amenable to genetic
      manipulation and directed DNA introduction. NCFM survives gastrointestinal tract
      transit in both healthy and diseased populations. NCFM inhibits aberrant crypt
      formation in mutagenized rats, indicative of activity that could decrease the
      risk of colon cancer. A blend of probiotic strains containing NCFM decreased the
      incidence of pediatric diarrhea. NCFM led to a significant decrease in levels of
      toxic amines in the blood of dialysis patients with small bowel bacterial
      overgrowth. At adequate daily feeding levels, NCFM may facilitate lactose
      digestion in lactose-intolerant subjects. Further validation of the probiotic
      properties of NCFM in humans and clarification of its mechanisms of probiotic
      action are needed to better understand the role this strain might play in
      promoting human health.

PMID- 11233017
TI  - Interactions of milk fat and milk fat fractions with confectionery fats.
AB  - The objectives of this study were to provide a better understanding of the
      effects of triacylglycerol (TAG) and non-TAG components (minor lipids) of milk
      fat on phase and crystallization behavior of binary mixtures of palm kernel oil
      (PKO) and the physical properties of corresponding compound coatings. Binary
      mixtures of a fractionated PKO with the different milk fats were examined for
      melting profiles, crystallization kinetics, and crystalline microstructures, and
      polymorphic changes during storage. Compound coatings were made with equivalent
      binary fat mixtures and measured for hardness and bloom formation. Milk fat and
      milk fat fractions affected crystallization rates of fractionated PKO, depending
      on the melting point of the fat. High-melting components resulted in more rapid
      crystallization, whereas the original milk fat and low-melting components
      inhibited crystallization. The crystal structure (e.g., number, size, shape) of
      the PKO crystals was influenced significantly by the addition of milk fat
      fractions and was influenced by the presence or absence of the minor lipids in
      milk fat. Milk fat and milk fat fractions had a softening effect on fractionated
      PKO, which was apparent in the binary mixtures as well as the compound coatings.
      In general, as the solid fat content (at 25 degrees C) of the binary mixtures
      increased, the hardness of the respective coatings increased. This also was
      related to an increased rate of bloom formation during storage.

PMID- 11233018
TI  - Composition and properties of milk and butter from cows fed fish oil.
AB  - A control diet and a fish oil diet were fed to 12 multiparous Holstein cows to
      determine how the incorporation of Menhaden fish oil in the diet would influence
      the fatty acid composition, especially the conjugated linoleic acid and
      transvaccenic acid, contents of milk and butter. The control diet consisted of a
      50:50 ratio of forage to concentrate, and the fish oil diet consisted of the
      control diet with 2% (on a dry matter basis) added fish oil. Milk from cows fed
      the control diet contained higher average concentrations of milk fat (3.37%)
      compared with milk from cows fed the fish oil diet (2.29%). Milk from cows fed
      fish oil contained higher concentrations of conjugated linoleic acid,
      transvaccenic acid, and total unsaturated fatty acids (0.68 and 2.51; 1.42 and
      6.28; and 30.47 and 41.71 g/100 g of fat, respectively). Butter made from the
      fish oil diet milk also had higher concentrations of conjugated linoleic acid,
      transvaccenic acid, and unsaturated fatty acids. Penetrometer readings indicated
      fish oil diet butters were softer at 4 and 20 degrees C than the control diet
      butters. Acid degree values were similar in the fish oil butters compared with
      the control butters. No significant difference was found in the flavor
      characteristics of milk and butter from cows fed the control and fish oil diets.
      Production of milk and butter with increased amounts of conjugated linoleic acid,
      transvaccenic acid, and other beneficial fatty acids may have a desirable impact
      on the health of consumers and lead to increased sales.

PMID- 11233019
TI  - Assessment of the coloring strength of brevibacterium linens strains:
      spectrocolorimetry versus total carotenoid extraction/quantification.
AB  - Brevibacterium linens is a major component of red-smear cheese microflora and
      imparts color to the cheese rind. The present study was done to evaluate
      carotenoid contents in 29 strains of this bacterium and to relate the color of
      the strains to the carotenoids present. A spectrocolorimeter was used to
      determine the color, and the carotenoid contents were determined by
      spectrophotorimetric measurement at 450 nm. Regression analysis was carried out
      on the color values a*, b*, and C* to determine which color value could be used
      to express the contents of carotenoids in B. linens biomass. The C* color value
      appeared to be the best estimate for correlation.

PMID- 11233020
TI  - Characterization of casein micelle precipitation by chitosans.
AB  - We have found that the addition of chitosan, a cationic polymer, on whole or skim
      milk produces destabilization and coagulation of casein micelles that takes place
      without changes in the milk pH or the stability of most whey proteins. The amount
      of lipids recovered in the chitosan-casein aggregates was similar or higher than
      that obtained with rennet or acid precipitation. Approximately 70% of milk Ca2+
      (approximately 750 mg/L) was found in the chitosan-induced aggregates, which is
      10 and 50% higher than the amounts observed with acid or rennet coagulations,
      respectively. Purified alpha, beta-, and kappa-caseins were extensively
      precipitated by different molecular weight chitosans at pH 6.8. The phosphate
      groups of caseins seem not to be relevant in this interaction because
      dephosphorylated alpha- and beta-caseins were equally precipitated with
      chitosans. Analysis by optical microscopy of the chitosan-casein complex reveals
      that the size of the aggregates increase as the molecular weight of chitosans
      increase. Hydrophobic and electrostatic interactions particpate in the
      association and coagulation of casein micelles with chitosans of different
      molecular weights. The phenomenon is observed over a broad range of temperature
      (4 to 70 degrees C) with a reduction in the concentration of chitosan needed to
      precipitate the caseins that parallels a reduction in the viscosity of the
      chitosan solutions. Taken together, the results indicate that the electrostatic
      interactions may contribute energetically to the association between the two
      biopolymers, but the hydrophobicity of the complex would be the key determinant
      in the overall energetics of the reaction.

PMID- 11233021
TI  - Implications of proposed changes in bulk tank somatic cell count regulations.
AB  - Several changes in bulk tank SCC (BTSCC) regulations were proposed at the 1998
      annual meeting of the National Conference of Interstate Milk Shippers (NCIMS) by
      the National Mastitis Council and other proponents. Proposals included 1) using a
      geometric mean BTSCC in place of the arithmetic mean, reducing the current limit
      for BTSCC from 750,000 to 400,000, and modifying current regulatory protocols.
      The purpose of this research was to evaluate possible impacts of proposed changes
      upon producers in warm climates. Data were monthly BTSCC values, provided by
      state regulatory agencies in West Texas, Louisiana, and Mississippi. Fifty
      producers from each state were selected by lot, and all 1998 monthly records were
      included (n = 1602). Computer simulation was used to compare regulatory actions
      that would have resulted under current and proposed regulations. Possible
      regulatory actions were 1) notification of noncompliance and 2) suspension of
      permits to sell milk. At the 750,000 BTSCC limit, both programs resulted in 41
      regulatory actions, but the proposed program had a higher rate of suspensions to
      notices. A twofold increase in regulatory actions per 100,000 incremental
      decrease in BTSCC limit below 750,000 resulted under both programs. Actual
      results could be lower due to the assumption that no management adjustments were
      made by producers in response to changes in regulations. However, the magnitude
      of increased actions against producers indicated that lowering limits quickly
      could be disruptive if producers failed to adjust management quickly and
      effectively to comply with lower limits.

PMID- 11233022
TI  - Monitoring of acidified milk gel formation by ultrasonic shear wave measurements.
      High-frequency viscoelastic moduli of milk and acidified milk gel.
AB  - In the present paper we describe the application of the thickness shear mode
      resonator technique for the measurement of viscoelastic parameters of milk and
      acidified milk gels in the megahertz frequency range. The technique provides
      information on the viscoelasticity of milk and milk gels in the time scale of 10(
      8) to 10(-7) s. The length scale of the measurements, determined by the depth of
      penetration and the wavelength of the shear wave, falls between the submicron and
      micron range. In milk acidified by glucono-delta-lactone we observed an increase
      in the high- and low-frequency loss modulus, G", below pH 5.1, indicating
      aggregation of casein particles into clusters. There was a sharp rise in high-
      and low-frequency storage (G') and loss (G") moduli between pH 4.85 and 4.7, as a
      result of gel network formation in acidified milk. Both G" and G' of milk gel in
      the megahertz frequency range are several orders higher than those we obtained at
      low frequencies (0.02 to 10 Hz) using dynamic rheology. The high-frequency (5 to
      25 MHz) viscosity of milk was found to be the same as at low frequencies.
      Overall, our results demonstrate the high sensitivity of the ultrasonic shear
      wave measurements to the changes in the rheological parameters in acidified milk
      during gelation.

PMID- 11233023
TI  - Short communication: Low levels of colostral immunoglobulins in some dairy cows
      with placental retention.
AB  - A test with 27 Holstein cows divided in two groups was conducted to evaluate the
      effects of placental retention (PR) on the colostral components. Fat and total
      protein content were similar in both groups, but immunoglobulins in cows with PR
      (7.58+/-6.72 g/L) were significantly lower than in cows without PR (15.13+/-8.56
      g/L). In contrast, casein levels were higher in cows with PR (38.61+/-17.05 g/L
      vs. 27.60+/-12.71 g/L) compared with cows without PR.

PMID- 11233024
TI  - Case-control study of risk factors for clinical mastitis in postpartum dairy
      heifers.
AB  - A case-control study was carried out to evaluate risk factors for clinical
      mastitis occurring in dairy heifers between 1 and 14 d postpartum. Case and
      control heifers were matched on herd; the control was the heifer that calved
      closest in time, before or after, the particular case. Data were analyzed by
      conditional logistic regression. The final multivariate model included 339 case
      control pairs. Blood in the milk, udder edema, teat edema, and milk leakage, all
      recorded at the time of parturition, were significant risk factors. Purchased
      heifers and heifers with skin lesions between udder and thigh were not at
      increased risk of clinical mastitis. Separate analysis of a subgroup of case
      control pairs identified teat edema, blood in the milk, and milk leakage at
      calving as risk factors for clinical mastitis caused by Staphylococcus aureus.

PMID- 11233025
TI  - Application of fuzzy logic in automated cow status monitoring.
AB  - Sensors that measure yield, temperature, electrical conductivity of milk, and
      animal activity can be used for automated cow status monitoring. The occurrence
      of false-positive alerts, generated by a detection model, creates problems in
      practice. We used fuzzy logic to classify mastitis and estrus alerts; our
      objective was to reduce the number of false-positive alerts and not to change the
      level of detected cases of mastitis and estrus. Inputs for the fuzzy logic model
      were alerts from the detection model and additional information, such as the
      reproductive status. The output was a classification, true or false, of each
      alert. Only alerts that were classified true should be presented to the herd
      manager. Additional information was used to check whether deviating sensor
      measurements were caused by mastitis or estrus, or by other influences. A fuzzy
      logic model for the classification of mastitis alerts was tested on a data set
      from cows milked in an automatic milking system. All clinical cases without
      measurement errors were classified correctly. The number of false-positive alerts
      over time from a subset of 25 cows was reduced from 1266 to 64 by applying the
      fuzzy logic model. A fuzzy logic model for the classification of estrus alerts
      was tested on two data sets. The number of detected cases decreased slightly
      after classification, and the number of false-positive alerts decreased
      considerably. Classification by a fuzzy logic model proved to be very useful in
      increasing the applicability of automated cow status monitoring.

PMID- 11233026
TI  - Measuring the financial risks of New York dairy producers.
AB  - The financial risks of a group of New York dairy producers were measured from
      1988 through 1997 and were decomposed by source of risk by two procedures.
      Decomposition of the variance suggested major contributors to variability in
      returns to New York dairy farms were variabilities in purchased feed quantities
      and milk production; milk price variability contributed substantially less.
      Similarly, decomposing the Gini measure of income dispersion indicated that milk
      revenues and purchased feed expenditures contributed most to farm return
      inequality over time. Controlling feed costs and maintaining high and stable milk
      production appear to be the principal approaches that dairy producers can use to
      control their financial risks.

PMID- 11233027
TI  - Negative energy balance does not decrease expression of leukocyte adhesion or
      antigen-presenting molecules in cattle.
AB  - Sixteen yearling Holstein steers were fed for 210 or 60% of maintenance
      requirements to impose positive or negative energy balance, respectively. Blood
      was collected and analyzed for serum concentration of nonesterified fatty acids
      (NEFA), and leukocytes were isolated and counted. Isolated leukocytes were then
      analyzed for expression of the adhesion molecules L-selectin (CD62L), Mac-1
      (CD11b and CD18), and major histocompatability complex (MHC) class I and class II
      molecules with immunostaining and flow cytometric analysis. Negative energy
      balance increased the concentration of NEFA in serum (P < 0.0001). Expression of
      CD62L on neutrophils was increased 14% during negative energy balance (P = 0.03).
      Energy balance did not affect expression of CD62L on any other cell types or
      expression of CD11b or CD18. Negative energy balance did not affect MHC class I
      expression but resulted in a small but significant increase in the expression of
      MHC class II (P = 0.03). The results of this study provide little evidence that
      nutritionally created negative energy balance impairs expression of CD62L, CD11b,
      and CD18 or expression of MHC class I or MHC class II molecules by resting bovine
      blood leukocytes.

PMID- 11233028
TI  - Effects of corn particle size and source on performance of lactating cows fed
      direct-cut grass-legume forage.
AB  - We conducted two experiments to evaluate the effects of corn supplementation,
      source of corn, and corn particle size on performance and nutrient utilization of
      lactating dairy cows. In experiment 1, treatments were 1) direct-cut grass-legume
      forage without supplement, 2) direct-cut forage plus 10 kg DM of ground dry
      shelled corn-based concentrate, and 3) direct-cut forage plus 10 kg DM of
      coarsely ground high moisture ear corn-based concentrate. In experiment 2,
      treatments were 1) direct-cut grass-legume forage plus 10 kg DM of ground dry
      shelled corn-based concentrate, 2) direct-cut forage plus 10 kg DM of coarsely
      ground high moisture ear corn-based concentrate, and 3) direct-cut forage plus 10
      kg of DM finely ground high moisture ear corn-based concentrate. Both experiments
      were designed as 3 x 3 Latin squares replicated three times. In experiment 1,
      yields of milk and milk protein increased with concentrate supplementation, but
      were not affected by source of corn. Solids-corrected milk yield tended to
      increase with grain supplementation. Dry matter intake increased with concentrate
      supplementation, but was not affected by source of corn or corn particle size.
      Corn supplements decreased ruminal pH and acetate to propionate ratio and
      increased ruminal propionate concentration. Grain supplements reduced ruminal
      ammonia concentration, increased concentration of urine allantoin, and increased
      the urinary allantoin to creatinine ratio. In the second study, fine grinding of
      high moisture corn reduced fecal starch plus free glucose levels and tended to
      increase its apparent digestibility. In both experiments, starch plus free
      glucose intake was higher on the diets with dry corn, but its utilization was not
      affected by source of corn.

PMID- 11233029
TI  - Effect of corn silage hybrid on dry matter yield, nutrient composition, in vitro
      digestion, intake by dairy heifers, and milk production by dairy cows.
AB  - Three corn hybrids, Mycogen TMF94, Cargill F337 (which contains a brown midrib
      trait), and Pioneer 3861 were compared in a plot trial, an intake trial, and a
      lactation trial. In the plot trial, the three corn hybrids were planted in
      replicated 15.2 x 385-m plots. Mycogen TMF94 and Cargill F337 had lower yields of
      dry matter (DM), higher concentrations of neutral detergent fiber, and higher in
      vitro true DM disappearance compared with Pioneer 3861. Mycogen TMF94 had a
      higher yield of DM than Cargill F337 despite having a lower plant population.
      However, Cargill F337 had a higher in vitro true DM disappearance than Mycogen
      TMF94. In the intake trial, six individually penned Holstein heifers were blocked
      and assigned randomly to one of three total mixed rations containing 79% (DM
      basis) Mycogen TMF94, Cargill F337, or Pioneer 3861 corn silages in replicated 3
      x 3 Latin squares. Heifers fed the Pioneer 3861-based TMR had lower DMI than
      heifers fed Mycogen TMF94 and Cargill F337-based TMR. In the lactation trial, 75
      midlactation Holstein cows were blocked and assigned randomly to one of three
      total mixed rations containing 31% (DM basis) Mycogen TMF94, Cargill F337, or
      Pioneer 3861 corn silages used in the intake trial. Milk production was highest
      for cows fed Cargill F337-based total mixed rations. It is concluded from this
      study that Mycogen TMF94 was higher yielding, but less digestible, and resulted
      in lower milk production by lactating cows than Cargill F337. In addition,
      Mycogen TMF94 had higher in vitro true DM disappearance, and similar DM yield and
      milk production by lactating cows when compared with Pioneer 3861.

PMID- 11233030
TI  - Effect of variation in proportion of cornmeal and steam-rolled corn in diets for
      dairy cows on behavior, digestion, and yield and composition of milk.
AB  - Sixty-six lactating multiparous Holstein cows (113+/-46 DIM) housed in a free
      stall facility were blocked and assigned randomly to one of three treatments to
      evaluate the effects on animal performance from feeding cornmeal, cornmeal mixed
      with steam-rolled corn in a ratio of 1:1 on dry matter basis, or steam-rolled
      corn. The only difference in the dietary ingredients was the type of corn, which
      was included in the total mixed ration (TMR) at 17% of dry matter. The densities
      (g/L) of cornmeal and steam-rolled corn were, respectively, 635 and 553. Diets
      were fed as TMR and were formulated according to the Cornell Penn Miner Dairy
      nutrition model. The TMR consisted of 40% forage and 60% concentrate on dry
      matter basis. The first 2 wk of the 8-wk study was a preliminary period, and data
      collected during this period were used as covariate in statistical analysis of
      production data collected during wk 6 to 8. Treatment diets were fed from wk 3 to
      8. Total tract digestibilities of dry matter, organic matter, crude protein,
      starch, and neutral detergent fiber were not significantly different among
      treatments. Cows fed TMR containing steam-rolled corn had higher body condition
      and ruminated longer. However, feeding cornmeal and steam-rolled corn together
      did not improve dry matter and nutrient digestion, milk yield, 3.5% fat-corrected
      milk yield, and percentage and yield of fat, crude protein, true protein, and
      lactose in milk, and milk urea nitrogen. In conclusion, feeding steam-rolled corn
      improved animal body condition and rumination. Partial or complete substitution
      of cornmeal by steam-rolled corn in diets for lactating dairy cows did not
      improve dry matter and nutrient digestion, milk yield, and milk composition.

PMID- 11233031
TI  - Effect of site and source of energy supplementation on milk yield in dairy cows.
AB  - The effect of infusing similar energy equivalents of starch into the rumen, or
      starch or oil into the abomasum was studied in four midlactation cows in a 4 x 4
      Latin square design experiment; controls were ruminally infused with water. Cows
      were fitted with cannulas in the rumen, abomasum, and ileum, and nutrient
      digestion in the rumen and small intestine was evaluated with Cr as a digesta
      marker. Ruminal infusions of starch, or abomasal infusions of starch or oil, were
      associated with a decrease in voluntary feed organic matter intake. Overall
      energy intake was reduced in oil-infused, but not in starch-infused cows.
      Nonstructural carbohydrate digestibility in the rumen and in the small intestine
      was similar among treatments. In abomasally infused cows 3.4 kg/d of
      nonstructural carbohydrates was apparently digested in the small intestine. Milk
      production was reduced in oil-infused cows, but the efficiency of milk energy and
      protein yield was unaffected by treatments. Plasma glucose, insulin, and IGF-1
      concentration, mammary glucose extraction rate, rumen ammonia and plasma urea,
      and arterial and mammary extraction rate of amino acids were all similar among
      treatments. Large quantities of starch can be digested in the rumen or small
      intestine of dairy cows. There appear to be no metabolic advantage to increasing
      the supply of starch to the rumen or the abomasum of mid-lactation dairy cows
      maintained on highly concentrated diets and exhibiting a positive energy balance.

PMID- 11233032
TI  - Prediction of energy balance in high yielding dairy cows with test-day
      information.
AB  - This study used a previously developed model to predict herd mean energy balance
      of the first 12 wk of lactation from test-day information. The predictions were
      compared with calculated energy balance based on feed analysis and to changes in
      body weight. Seven independent feeding trials including 43 diets (519 lactations,
      254 cows; 1987 to 1996) were used. Conventional diets were discriminated from
      nonconventional diets by significant differences between mean calculated energy
      balance of subtrial diets versus control diets. The total difference between
      group means of predicted minus calculated energy balance was positive throughout
      the observed lactation period. It was lowest (5 to 9 MJ of net energy for
      lactation) during negative energy balance of the conventional diets in wk 2 to 7
      when 18 to 50% of the total difference was due to random variation. Because of
      this difference, both predicted and calculated energy balances were compared to
      body weight change as a reference for true energy balance. Body weight change was
      adjusted for rumen fill. While calculated energy balance tended to be negative at
      times when cows gained weight, predicted energy balance was positive. Cows fed
      nonconventional diets gained weight, while calculated energy balance was
      extremely negative, whereas predicted energy balance based on test-day
      information was positive. We concluded that the prediction difference was
      relatively small when standard rations were used, and that nonconventional
      rations biased predicted energy balance to a lesser extent than calculated energy
      balance. Estimating energy balance based on test-day information appears
      feasible.

PMID- 11233033
TI  - Association between milk urea nitrogen and fertility in Ohio dairy cows.
AB  - The purpose of this study was to evaluate the association between milk urea
      nitrogen (MUN) and fertility of dairy cows using field data. The data came from
      24 dairy herds belonging to Ohio Dairy Herd Improvement Cooperative Inc.
      Reproductive data and MUN measurements from cows that calved between June 1998
      and May 1999 and that had been bred at least once were included in the study.
      Survival analysis, using the Cox proportional hazards model, was performed and
      days from calving to conception or to the end of the study was used as the
      outcome. Cows that had not been reported pregnant during the study were
      considered censored. The mean of monthly MUN values of cows before conception (or
      the end of the study for censored cows) was used to reflect the MUN status of a
      cow. Animals were categorized into quartiles based on MUN values in these data.
      Parity, calving season, peak milk yield, number of services, and herd were
      included in the models as fixed effects. Cows with MUN levels below 10.0 were 2.4
      times more likely and cows with MUN levels between 10.0 and 12.7 mg/dl were 1.4
      times more likely to be confirmed pregnant than cows with MUN values above 15.4
      mg/dl. Our results indicate that increasing MUN levels appear to be negatively
      related to dairy cow fertility and are associated with a lower risk of detectable
      pregnancy at herd checks. They also suggest that the levels of MUN that are
      adversely associated with fertility might be lower than reported earlier.

PMID- 11233034
TI  - Rumen undegradable protein, rumen-protected choline and mRNA expression for
      enzymes in gluconeogenesis and ureagenesis in periparturient dairy cows.
AB  - The objective of this study was to profile mRNA expression of argininosuccinate
      synthetase (AS) and ornithine transcarbamylase (OTC), two enzymes that
      participate in the formation of urea in liver and compare these with changes in
      mRNA for pyruvate carboxylase (PC) and phosphoenolpyruvate carboxykinase (PEPCK)
      during the periparturient period in dairy cows. Forty-eight multiparous Holstein
      cows were fed isoenergetic prepartum diets that contained 10% RDP and either 4.0%
      RUP or 6.2% RUP and either 0, 6, or 12 g/d of rumen-protected choline (RPC) as
      CapShure (Balchem Corp., Slate Hill, NY). After calving cows received a common
      diet and continued RPC as per their prepartum assignments. Liver biopsies were
      obtained on d -28, -14, 1, 28, and 56 relative to calving, and the abundances of
      AS, OTC, PC, PEPCK, and 18S mRNA were determined by Northern blot analysis of
      total RNA. The abundance of OTC mRNA was lowest at calving and was decreased by
      RPC and 6.2% RUP feeding. Feeding 6.2% RUP did not alter AS, PC, or PEPCK mRNA.
      The expression of AS mRNA increased and PEPCK mRNA tended to increase from
      calving to 56 DIM. Pyruvate carboxylase mRNA increased more than twofold at
      calving. The data indicated adaptation to lactation for gluconeogenic enzymes
      that is not matched in direction and magnitude by changes in mRNA for urea cycle
      enzymes. Feeding additional protein, as RUP, failed to induce mRNA for key
      enzymes in gluconeogenesis or ureagenesis.

PMID- 11233035
TI  - Effects of supplemental dietary biotin on performance of Holstein cows during
      early lactation.
AB  - This study determined the effects of supplemental dietary biotin (0, 10, or 20
      mg/d) on performance of Holstein cows (n = 45; 18 primiparous and 27
      multiparous). Treatments started at 14 d prepartum and continued until 100 d in
      milk (DIM). Blood samples were taken at 14 d prepartum, and blood and milk
      samples were taken at calving, and 30, 60, and 100 DIM. Dry matter intake during
      lactation was not different across treatments (19.7 kg/d). Milk production
      linearly increased with biotin supplementation (36.9, 37.8, and 39.7 kg/d for 0,
      10, and 20 mg/d of supplemental biotin, respectively). Biotin supplementation did
      not affect milk fat and true protein percentages or fat yield but linearly
      increased true protein yield. Supplemental biotin increased concentrations of
      biotin in plasma and milk at all time points. Concentrations of biotin in plasma
      and milk (colostrum) at calving were higher than at other time points for cows
      fed supplemental biotin. In an ancillary experiment, plasma biotin concentrations
      were not as high when cows were fed 20 mg/d of supplemental biotin for 14 d
      during the middle of their dry period as when cows were fed 20 mg/d of biotin for
      the last 14 d of gestation. This suggests that events associated with parturition
      altered plasma biotin concentrations. Plasma concentrations of glucose, insulin,
      nonesterified fatty acids, and molar proportions of ruminal volatile fatty acids
      were not affected by biotin supplementation. Biotin supplementation had no effect
      on change in body weight or condition score. Supplemental biotin linearly
      increased milk and protein yields, however, the mode of action that caused these
      increases was not determined.

PMID- 11233036
TI  - Associations between casein haplotypes and first lactation milk production traits
      in Finnish Ayrshire cows.
AB  - The objective of this study was to estimate the effects of beta-kappa-casein (CN)
      haplotypes on first-lactation milk production traits. The beta-kappa-CN
      haplotypes were deduced using information on beta- and kappa-CN genotypes of cows
      and their sires for 16,973 Finnish Ayrshire cows that had at least nine paternal
      half sibs. Effects of CN haplotypes on milk production traits were estimated for
      one haplotype at a time using an animal model, which included the fixed effects
      for calving year and month, age at calving, days open, beta-lactoglobulin, and a
      beta-kappa-CN haplotype. Differences in milk production traits were also
      estimated between haplotype combinations A1A+A2B and A1B+A2A within beta-kappa-CN
      genotype A1A2AB and between combinations A1E+A2A and A1A+A2E within genotype
      A1A2AE. The beta-kappa-CN haplotypes A2A and A2B were associated with high milk
      and protein yields and low fat content, and those that included the beta-CN A1
      allele were associated with low yields and high fat content. Protein content was
      affected by the kappa-CN locus; haplotype A1B was associated with high protein
      content and A1E was with low protein content. The haplotype combination A1A+A2B
      was associated with 140 kg more milk yield (P = 0.045) and 0.03 percentage units
      less protein content (P = 0.055) than combination A1B+A2A, and combination
      A1A+A2E showed 0.02 percentage units greater protein content (P = 0.098) than
      A1E+A2A. These results indicate that genes linked to the CN loci contribute to
      the variation in milk yield and protein content.

PMID- 11233037
TI  - Phenotypic trends in incidence of stillbirth for Holsteins in the United States.
AB  - The objectives for this study were to determine 1) if there was a trend in
      stillbirths for the U.S. Holstein population, 2) if stillbirths are the same
      trait in primiparous and multiparous cows, and 3) what was the role of dystocia
      in stillbirths. A sample of 666,341 births from the MidStates Dairy Records
      Processing Center and the National Association of Animal Breeders was used to
      examine the influence of sire, herd, year, season, sex of calf, parity of dam,
      calving ease, and gestation length on the survival of the calf. Parity was scored
      as an ordered variable (1, 2, 3+). Calving ease was scored on a scale of 1 (no
      assistance) to 3+ (needed assistance). An increasing trend in stillbirths was
      found in primiparous and multiparous cows. The percentage of stillborn calves in
      primiparous cows increased from 9.5 in 1985 to 13.2 in 1996. Stillbirths in
      multiparous cows increased from 5.0 to 6.6% from 1985 to 1996. Variation about
      the trend was greater in primiparous cows than in multiparous cows. Dystocia was
      a major determinant of stillbirth incidence, but the association was stronger in
      primiparous cows. Sex of calf had different associations with stillbirth
      incidence in primiparous and multiparous cows. Gestation length and season of
      birth also had significant associations with stillbirth incidence. Logistic
      regression models with fixed and random effects were fit to the data to preserve
      the binary nature of the stillbirth response. The expected probability of
      stillbirths for an average herd and sire was 10% for primiparous cows and 5% for
      multiparous cows. Replacement of stillborn calves is a substantial cost to the
      dairy industry at more than $125.3 million per year. Because of the increasing
      incidence of stillbirths, these costs have increased by $75.9 million from 1985
      to 1996.

PMID- 11233038
TI  - On-farm batch pasteurization destroys Mycobacterium paratuberculosis in waste
      milk.
AB  - A recent dairy survey conducted in 1996 by the National Animal Health Monitoring
      System suggests between 20 and 40% of dairy herds in the United States have some
      level of Johne's disease. This figure will continue to increase unless producers
      implement management regimes that will help control the spread of this disease
      within their herds. The neonatal calf is the target for infection with
      Mycobacterium paratuberculosis, the causative agent of Johne's disease. Calves
      become infected via exposure to the bacterium through contaminated feces,
      bedding, colostrum, and milk. Shedding of viable M. paratuberculosis has been
      documented in the colostrum and milk of infected dams. This study evaluated the
      efficacy of on-farm pasteurization to destroy M. paratuberculosis in waste milk
      fed to calves to circumvent this mode of transmission. In three replicate
      experiments, waste milk was experimentally inoculated with M. paratuberculosis
      and heated at 65.5 degrees C for 30 min. No viable bacteria were recovered after
      28 wk of incubation. These results suggest that batch pasteurization of waste
      milk contaminated with M. paratuberculosis was effective at generating a clean
      product to feed to young calves.

PMID- 11233039
TI  - A comparison of free-stall barns used by modernized Wisconsin dairies.
AB  - A primary objective of the Wisconsin Dairy Modernization Survey was to compare
      features of free-stall barns available to dairy producers. This study used data
      from a large random sample of expanding dairy farms to determine whether the
      theoretical benefits of particular free-stall configurations bear out under on
      farm conditions. Comparisons were made among herds using free-stall barns as
      their primary housing for new versus remodeled facilities, barn design, bedding
      used, feed-delivery design, manure removal strategies, animal restraint,
      maternity areas, overcrowding, and cooling methods. Producers who made the
      transition from tie-stall housing to free-stall housing were satisfied with this
      decision. New free-stall barns provided a more desirable environment for the
      herds than remodeled free-stall barns, although initial investments were higher.
      When new free-stall barns were compared, herds with four-row barns had higher
      production, lower somatic cell count, and higher stocking rates than herds with
      six-row barns. Respondents were more satisfied with four- and six-row barns than
      with two- and three-row barns. Respondents felt sand provided some advantages for
      cow comfort, while satisfaction with bedding cost and manure handling was higher
      with mattresses. Dairy Herd Improvement data showed no difference in milk
      production or somatic cell count for producers who chose sand or mattress-based
      free stalls. Respondents were more satisfied with the use of drive-through
      feeding than other feed-delivery designs. Most producers chose to use tractor
      scrapers to remove manure; however, producers who used automated systems were
      more satisfied with manure management. Few differences were observed when
      comparing self-locking head gates to palpation rails. Overcrowding did not have
      any adverse affect on production or user satisfaction with feed intake or cow
      comfort. Using supplemental cooling appeared to facilitate higher production.

PMID- 11233041
TI  - [Female patient with acute generalized exanthematous pustulosis].

PMID- 11233042
TI  - [Boy with dermatosparaxis (Ehlers-Danlos type VIIC)].

PMID- 11233043
TI  - Extracorporeal photopheresis for the treatment of lung allograft rejection.
AB  - OBJECTIVES: Acute and chronic rejection continue to limit the survival of lung
      transplant recipients. Extracorporeal photopheresis has evolved as a possible
      therapy for patients with acute nd chronic lung allograft rejection. METHODS: We
      retrospectively reviewed 14 patients diagnosed with BOS who underwent therapy
      with extracorporeal photopheresis. RESULTS: Three patients were classified as BOS
      0'b', five as BOS 1, three as BOS 2, and, three as BOS 3 at the time of
      diagnosis. Of the patients with BOS 0'b' or BOS 1 seven remain alive and one died
      of lung cancer. Two have progressed to BOS 2. Of the patients with BOS 2 or 3,
      four have died of BOS, one died of lung cancer, and one was re-transplanted. In
      three patients with BOS and concurrent acute rejection, therapy with
      extracorporeal photopheresis led to the resolution of the acute rejection
      episode. Two of the 14 patients developed line related sepsis. CONCLUSION:
      Extracorporeal photopheresis appears to be a promising therapy for patients with
      early BOS. It may also have a role in the treatment of acute lung allograft
      rejection.

PMID- 11233044
TI  - How good is the Dutch health-care system?

PMID- 11233045
TI  - [New views on studies of Klotho gene and biology].

PMID- 11233046
TI  - Cancer heterogeneity and its biologic implications in the grading of urothelial
      carcinoma.

PMID- 11233047
TI  - Long-term results of intravesical bacillus Calmette-Guerin therapy for stage T1
      superficial bladder cancer.

PMID- 11233048
TI  - The effects of epilepsy and its treatment on sexual and reproductive function.

PMID- 11233049
TI  - The value of testing pudendal nerve conduction in evaluating erectile dysfunction
      in diabetics.

PMID- 11233050
TI  - Comparison of recommendations by urologists and radiation oncologists for
      treatment of clinically localized prostate cancer.

PMID- 11233051
TI  - Re: Chen et al. Cardiac troponin T alterations in myocardium and serum of rats
      after stressful, prolonged intense exercise. J Appl Physiol 88:1749-1755, 2000.

PMID- 11233052
TI  - [Bicom--bioresonance therapy].

PMID- 11233053
TI  - Stop the dollar worshiping.

PMID- 11233054
TI  - Regulation now misguided.

PMID- 11233055
TI  - MedBytes.

PMID- 11233056
TI  - Fighting back.

PMID- 11233057
TI  - Genetic evaluation of cancer: the importance of family history.
AB  - Although the etiology of most cancers is thought to be sporadic and
      multifactorial, 5% to 10% of breast, ovarian, and colon cancers result from
      defects or mutations in specific genes inherited by a person through the
      germline. Distinctions may be made between hereditary and sporadic cancers.
      Because the risk of developing cancer is greater for persons from a hereditary
      cancer family than for the general public, these people should be considered for
      early detection and prevention options. Testing for selected cancer genes is
      available commercially, and physicians must determine which patients are
      appropriate candidates for these tests. Risk-reduction strategies and options for
      high-risk patients as well as legal and ethical issues pertaining to genetic
      counseling and testing will be considered.

PMID- 11233058
TI  - Colorectal cancer screening: the old and the new.
AB  - As the second leading cancer killer of Americans, colorectal cancer represents a
      serious health threat to all Americans. All health care providers and patients
      should demand colorectal cancer screening, which has been shown to decrease the
      incidence and mortality of the disease through the detection and removal of the
      cancer's precursor lesion, the adenomatous polyp. Colonoscopy is the most
      effective screening tool because it identifies and treats more polyps than any
      other screening tool available today. However, cost issues have led to
      considerable controversy regarding its universal application as a screening tool.

PMID- 11233059
TI  - Optimum screening interventions for gynecologic malignancies.
AB  - The availability of screening modalities and improvements in prevention have
      reduced the risk of developing some cancers over the last few decades. Methods
      for optimal screening of gynecologic cancers are still being investigated.
      Cervical cancer is the only gynecologic malignancy for which a screening modality
      is widely accepted and recommended to all women. Annual screening of cervical
      cells has been shown to reduce the incidence of cervical cancer by 78%.
      Unfortunately, more than 50% of cervical cancers occur in women who have not been
      screened optimally. In the year 2000, an estimated 12,800 women developed
      cervical cancer. Of these women, 89% were seen by a physician but not screened.
      Vaginal cancer is associated with a similar etiology, pathobiology, and
      symptomatology as is cervical cancer. Vaginal dysplasia and cancer can also be
      detected by the Pap test, but the prevalence of the disease is low. Endometrial
      carcinoma is the most common gynecologic cancer. The widespread availability of
      outpatient biopsy devices has been the most significant advance in the early
      diagnosis of corpus cancers. Ovarian cancer is the gynecologic malignancy
      associated with the highest death rate. No modality has been shown as an
      effective screening method for this cancer. Women with a family history of
      ovarian cancer may benefit from combined modality screening; prophylactic
      oophorectomy should be offered to those with hereditary ovarian cancer syndromes.
      A complete physical examination by the physician offers the best method for early
      detection of vulvar cancer. Awareness and implementation of recommended screening
      guidelines for gynecologic cancers by primary care and specialty physicians can
      decrease the incidence and mortality of cervical cancer. Including the genital
      tract in the complete examination of the female patient could decrease markedly
      the mortality from the other gynecologic cancers.

PMID- 11233060
TI  - Nonmelanoma skin cancer: today's epidemic.
AB  - The practicing physician encounters many benign and malignant skin neoplasms
      daily. Basal cell carcinoma and squamous cell carcinoma represent the vast
      majority of the malignant tumors. Identification of predisposing factors,
      intrinsic and extrinsic, can decrease future tumor development. Early
      recognition, biopsy confirmation, and treatment selection can reduce patient
      morbidity.

PMID- 11233061
TI  - Early detection of prostate cancer: is PSA a reliable option?
AB  - A close relationship exists between prostate volume and prostate-specific antigen
      (PSA). Clinical decisions must be determined based on the variability of PSA.
      Screening with the PSA assay has contributed to early detection of prostate
      cancer. Some important undetermined issues are the optimal cutoff values of PSA,
      the proportion of free to total PSA, and the clinical usefulness of complexed
      PSA. Current articles demonstrating novel markers (human kallikrein-2, BPSA, and
      pro PSA) and artificial neural networks are introduced.

PMID- 11233062
TI  - Techniques for smoking cessation: what really works?
AB  - Cigarettes (and tobacco) represent the most significant lifestyle risk for
      cancer, accounting for more than 400,000 deaths in the United States each year.
      The cancer risk in smokers is proportional to the number of cigarettes smoked in
      the patient's lifetime; therefore, smoking cessation is always in the best
      interest of a smoker's health. Physicians can play a crucial role in the success
      of their patients' smoking cessation programs. Experimental studies,
      observational studies, and the experience of seasoned physicians have identified
      a number of effective strategies that any physician can use. This article
      presents several brief counseling approaches and a summary of pharmacologic
      treatments that can be incorporated into office and hospital practice.

PMID- 11233063
TI  - Complementary therapies for cancer patients: what works, what doesn't, and how to
      know the difference.
AB  - Cancer patients, with their multiple symptoms and layers of suffering, are
      presenting many challenges to the treating physician and are turning to
      complementary mind-body therapies in increasing numbers. The utilization of mind
      body medicine and other complementary therapies is growing at rates faster than
      Western medicine, and physicians are more commonly being questioned about
      potential benefits and risks of these therapies. This article discusses hypnosis
      and mind-body approaches in the care of the cancer patient, and offers
      suggestions regarding the evaluation of complementary medicine therapies.

PMID- 11233064
TI  - Breast cancer: screening and early detection.
AB  - A comprehensive program for breast cancer screening and early detection has a
      number of components. First, an understanding of the magnitude of the breast
      cancer problem and the natural history of breast cancer is essential. Appropriate
      screening guidelines must be identified and adopted into practice. Screening
      recommendations must be promoted actively. While breast cancer screening
      guidelines can be applied broadly to the general population, patients who are at
      increased risk must be identified through formal risk assessment. For those at
      increased risk, earlier screening and prevention strategies can be recommended.
      Physicians must be prepared to manage the abnormalities identified in screening
      and make appropriate referrals for treatment. Finally, patients identified with
      cancer must be staged accurately, as this staging will determine the prognosis.

PMID- 11233065
TI  - Role of anaerobic bacteria in pyomyositis in children.

PMID- 11233066
TI  - In defense of discrepant analysis.

PMID- 11233067
TI  - Ascertainment bias in case-control studies of cancer screening.

PMID- 11233077
TI  - Antenatal glucocorticoid treatment does not reduce chronic lung disease among
      surviving preterm infants.
AB  - BACKGROUND: Antenatal glucocorticoid treatment (AGT) is associated with a number
      of postnatal benefits to the preterm infant, including reduced risk of
      respiratory distress syndrome, patent ductus arteriosus, intraventricular
      hemorrhage, and necrotizing enterocolitis. OBJECTIVE: To evaluate the hypothesis
      that maternal AGT not only reduces the risk of surfactant deficiency but also
      reduces the occurrence of chronic lung disease (CLD) among surviving preterm
      infants. STUDY DESIGN: Case-referent study of 1454 very low birth weight infants
      born between January 1991 and December 1993 at 4 university medical centers.
      RESULTS: Rates of AGT varied among the 4 centers (11%-69%), as did rates of CLD
      (4%-21%), defined as a requirement for supplemental oxygen at 36 weeks'
      postmenstrual age. CLD rates at each center, however, did not vary with the rate
      of AGT exposure. In multivariate logistic regression analyses, AGT did not
      contribute significantly to CLD risk. CONCLUSION: AGT may play a less prominent
      role in modifying CLD risk than other factors such as biologic immaturity,
      infection, or neonatal intensive care unit practices, such as mechanical
      ventilation, continuous positive airway pressure, and surfactant replacement
      therapy.

PMID- 11233078
TI  - Ageing, gerontogenes, and hormesis.
AB  - Evolutionary theories of ageing and longevity argue against the existence of
      specific genes that cause ageing. However, genes whose altered activity
      influences ageing and longevity, may be termed gerontogenes. Several putative
      gerontogenes have been identified in various ageing systems, including the
      Drosophila, budding yeast, nematodes and cells in culture. Since ageing is
      characterized by a progressive failure of maintenance and repair, it is reasoned
      that genes involved in homeodynamic repair pathways are the most likely candidate
      gerontogenes. A promising approach for the identification of critical
      gerontogenic processes is hormesis-like positive effects of stress. Stimulation
      of various repair pathways by mild stress has significant effects on delaying the
      onset of various age-associated alterations in cells, tissues and organisms.

PMID- 11233079
TI  - Surface protein changes in goat spermatozoa during capacitation.
AB  - Polypeptides of goat sperm surface before and after capacitation were examined by
      radiolabelling and immunologically using polyclonal antisera. Radioiodination
      revealed five protein bands having mol wt of 14.8, 72.4, 81, 100 and 128 kDa in
      uncapacitated ejaculated spermatozoa and only three bands of 23.4, 27 and 72.4
      KDa in capacitated spermatozoa. The protein band with mol wt 72.4 kDa was only
      feebly iodinated in uncapacitated sperm surface but in capacitated spermatozoa it
      was heavily labelled. Western blot analysis of detergent-extracted proteins using
      gamma-globulin fraction of antisera raised against purified goat sperm plasma
      membrane revealed six antigens (17.8, 29.1, 33.4, 45.6, 85.1, 123.2 kDa) in
      uncapacitated spermatozoa, four (26, 32.1, 40.1, 45.6 kDa) in capacitated
      spermatozoa and only one (45.6 kDa) in acrosome-reacted spermatozoa. High mol wt
      proteins were more numerous on the surface of uncapacitated spermatozoa while the
      capacitated spermatozoa had relatively low mol wt proteins. An apparent effect of
      capacitation is the metabolism and reorganisation of proteins on goat sperm
      surface. Polypeptides on capacitated sperm surface revealed through
      radiolabelling and polyclonal antisera may have a likely receptor(s) role in the
      recognition and binding to homologous zona pellucida during fertilization.

PMID- 11233081
TI  - Effect of 2-deoxy-D-glucose on metabolism of glycosaminoglycans in normal and
      hypercholesterolemic rats.
AB  - Carbohydrates are the integral parts of glyco-conjugates and play an important
      role in cellular functions. 2-Deoxy-D-glucose (2-dGlc) is a sugar analogue of
      glucose and mannose and is reported to inhibit the lipid-linked saccharide
      formation involved in N-linked glycosylation of proteins. Administration of 2
      dGlc (1 mg/100 g body weight) produced a decrease in the tissue total
      glycosaminoglycans level. We found that the activity of the enzymes involved in
      the biosynthesis of precursors of glycosaminoglycans (GAG) decreased, but that of
      the degrading enzymes increased. Thus, the decreased levels of GAG in tissues in
      2-dGlc-administered rats occurs via enhanced degradation as well as decreased
      synthesis.

PMID- 11233080
TI  - Analgesic and anti-inflammatory effects of phosphodiesterase inhibitors.
AB  - The aim of the present study was to investigate the role of phosphodiesterase
      (PDE) enzyme inhibitors namely rolipram and theophylline in pain and inflammation
      in experimental animals. Rolipram, a selective PDE IV inhibitor and theophylline
      a nonspecific PDE inhibitor exerted dose dependent analgesic and anti
      inflammatory effect against acetic acid-induced writhing in mice and carrageenan
      induced paw edema in rats, respectively. Nimesulide (1, 2 mg/kg) produced
      significant anti-inflammatory effect. Further, nimesulide (0.5 mg/kg) potentiated
      analgesic effect of rolipram but it failed to modulate the anti-inflammatory
      effect of PDE inhibitors. Present study suggests that PDE enzymes might be
      playing a role in nociceptive and inflammatory responses in animals.

PMID- 11233082
TI  - Anxiolytic activity of Indian Hypericum perforatum Linn: an experimental study.
AB  - The putative anxiolytic activity of 50% ethanolic extract of Indian Hypericum
      perforatum (IHp) was investigated in rats using various experimental paradigms of
      anxiety viz. open field exploratory behaviour (OFB), elevated plus maze (EPM),
      elevated zero maze (EZM), novelty induced suppressed feeding latency (FL) and
      social interaction (SI) tests. Pilot studies indicated that single dose
      administration of IHp had little to no acute behavioural effects, hence the
      extract of IHp was administered orally at different dose levels once daily for
      three consecutive days, while lorazepam (LR) (0.5 mg/kg, i.p.) was administered
      acutely. IHp extract (100 and 200 mg/kg, p.o.) showed significant anxiolytic
      effects on all the paradigms of anxiety. The results indicate that IHp and LR
      induced a significant increase in open field ambulation and slight increase in
      rearings and activity in centre, whereas grooming and fecal droppings remain
      unchanged. In EPM, significant augmentation of open arm entries, open arm/closed
      arm entries ratio and time spent on open arms was noted in IHp treated rats. In
      EZM test, significant increase in time spent on open arms and entries in open
      arms were observed, whereas slight increase in head dips and stretched attend
      postures were also observed. IHp and LR significantly attenuated the novelty
      induced increase in feeding latency. IHp treated rats also showed significant
      increase in social interaction in the novel environment. The IHp extracts showed
      consistent and significant anxiolytic activity in all the tests. The effects
      induced by 50% ethanolic extract of IHp were less marked than those of lorazepam
      were.

PMID- 11233083
TI  - Comparison of skin permeability of drugs in mice and human cadaver skin.
AB  - In vitro percutaneous absorption of four antihypertensive drugs were carried out
      across the mice and human cavader skin in order to compare their skin
      permeability. An interesting trend was noticed in these experiments. Poorly water
      soluble drug prazosin hydrochloride showed 13 times enhanced flux in the mice
      skin whereas the steady-state flux of the water soluble drug propranolol
      hydrochloride was almost same in both human cadaver and mice skin. The permeation
      rate of prazosin hydrochloride and propranolol hydrochloride through the human
      cadaver skin fluctuated widely over time, but in mice skin, distinct trends were
      noticed. The study indicates that the overall permeation rate in mice skin is
      higher than that in the cadaver skin and the meeting of the target-flux in mice
      skin does not guarantee its good permeability in human skin.

PMID- 11233084
TI  - Effect of diagnostic X-rays on somatic chromosomes of occupationally exposed
      workers.
AB  - Investigations were carried out to estimate the level of radiation exposure
      effect of X-ray machines on 40 male personnel handling diagnostic X-ray machines
      and compared to 38 matched, unexposed, normal controls. The actual accumulated
      radiation doses were not disclosed. As compared to controls the exposed persons
      showed highly significantly increased levels (P < 0.01) of chromosome aberrations
      (0.68%-2.67%). Frequencies of sister chromatid exchanges (5.80-6.20) and the
      levels of aneuploidy (2.27-2.37) were also increased a little, but did not show
      statistically significant effect of exposure. Satellite associations (7.84-16.25)
      and mitotic index (5.14-6.07) showed a significant increase (P < 0.05) in exposed
      individuals. The statistically significant increase in the frequencies of
      chromosomal aberrations and satellite associations in X-ray personnel underscores
      the need of adopting measures to avoid or at least minimiZe overexposure to X
      irradiation.

PMID- 11233085
TI  - Response of sugar interconversion, starch and protein accumulation to supplied
      metabolites during pod filling in chickpea.
AB  - Detached chickpea inflorescences bearing pods at 20 days after flowering (DAF)
      were cultured for 5 days in complete liquid medium supplemented separately with
      asparate, myo-inositol, alpha-ketoglutarate and phytic acid. Effect of these
      metabolites on sugar interconvestion and starch and protein accumulation in
      developing pods was studied. Substituting asparate (62.5 mM) for glutamine in
      culture medium decreased relative proportion of sucrose in all pod tissues but
      increased the level of sugars, starch and protein in pod wall and cotyledons. In
      cotyledons, whereas myo-inositol (75 mM) reduced the accumulation of starch
      without affecting protein level, alpha-ketoglutarate (44 mM) increased both
      starch and protein accumulation. Both myo-inositol and alpha-ketoglutarate
      increased relative proportion of sucrose in cotyledons. Phytic acid (1 mM)
      decreased in cotyledons 14C incorporation from glucose into EtOH extract
      (principally constituted by sugars), amino acids and proteins but increased the
      same into starch. In cotyledons, phytic acid also increased 14C incorporation
      from glutamate into amino acids but this increase was negatively correlated with
      protein synthesis. Phytic acid decreased the relative distribution of 14C from
      glucose and glutamate into sucrose from pod wall but enhanced the same into EtOH
      extract from embryo. Based on the results, it is suggested that mode of metabolic
      response to exogenously supplied metabolites widely differs in pod tissues of
      chickpea.

PMID- 11233086
TI  - Chemical characterization of fungal siderophores.
AB  - Siderophores of twenty fungi belonging to Zygomycotina (5 Mucorales),
      Ascomycotina (7 aspergilli, 6 penicillia, Neurospora crassa) and Deuteromycotina
      (Fusarium dimerum) were examined for their chemical nature. Siderophores produced
      by fungi other than Mucorales were all hydroxamates. Mucorales produced
      carboxylate siderophores. Catecholate type of siderophores were not detectable.
      Hydroxamate siderophores were mostly (9 out of 15) trihydroxamates, while six
      were dihydroxamates. Monohydroxamate nature was not shown by any of the 15 test
      fungal siderophores. In ligand properties, 12 out of 15 hydroxamate siderophores
      formed hexadentate ligands, while two formed tetradentates and one bidentate.
      There was good correlation between number of hydroxamate groups and ligand
      property.

PMID- 11233087
TI  - Transgenic strategies for genetic improvement of Basmati rice.
AB  - Transgenic approach offers an attractive alternative to conventional techniques
      for the genetic improvement of Basmati rice because they enable the introduction
      of one or more genes into a leading cultivar without affecting its genetic
      background. During the last ten years, a rapid progress has been made towards the
      development of transformation methods in rice. Several transformation methods
      including Agrobacterium, biolistic, and DNA uptake by protoplasts, have been
      employed to produce transgenic rice. An array of useful genes is now available
      and many of these have already been transferred in rice to improve the resistance
      against biotic and abiotic stresses. In Basmati rice, a beginning has already
      been made regarding the development of tissue culture protocols, transformation
      methods and production of useful transgenic plants. The application and future
      prospects of transformation technology to engineer the resistance against insect
      pests (stem borer, leaf folder, brown plant hopper, gall midge), fungal diseases
      (blast, bakanae/foot, rot), bacterial diseases (bacterial leaf blight, sheath
      blight), abiotic stresses (salinity and drought) and improved nutritional quality
      (accumulation of provitamin A and essential amino acids in endosperm) in Basmati
      rice, have been addressed.

PMID- 11233088
TI  - Growth inhibitory and antifeedant activity of extracts from Melia dubia to
      Spodoptera litura and Helicoverpa armigera larvae.
AB  - The growth inhibitory activity and deterrency of Melia dubia (Meliaceae) extracts
      to Spodoptera litura and Helicoverpa armigera were investigated. Artificial diet
      bioassays using neonate larvae of both S. litura and H. armigera indicated that
      dichloroethane (DCE) and methanol (Me) extracts of M. dubia inhibited growth in a
      dose dependent manner. DCE and Me-5II fractions also resulted in 50% deterrency
      at concentrations of 22.5 and 16.8 micrograms/cm2 respectively against S. litura
      larvae in a leaf disc-choice test. The DCE-5 fraction was found to be more toxic
      to larvae (LC50 of 0.65%) than the Me-5II (LC50 of 0.8%), 72 hr after topical
      application. Both fractions lack contact toxicity, but the deterrent effect
      persisted for at least 60 hr under laboratory conditions. Although salannin was
      isolated from the DCE fraction to show antifeedant activity, the physico-chemical
      characteristics of the active fractions DCE-5 and Me-5II were not identical with
      either salannin or azadirachtin.

PMID- 11233089
TI  - In vitro strategies for selection of eye-spot resistant sugarcane lines using
      toxins of Helminthosporium sacchari.
AB  - In vitro strategies were applied for the selection of eye-spot resistant variants
      from susceptible sugarcane cultivar Co 419 Different selective units (callus and
      leaf) of the susceptible cultivar were subjected to sub-lethal to lethal doses of
      toxins (culture filtrate and partially purified toxin) of H. sacchari, with the
      objective of improving the efficacy of in vitro selection protocols. All the
      selective units gave more or less similar response with culture filtrate, but a
      distinct response was observed when leaf was subjected to partially purified
      toxin treatment. The response was characterised by the degree of resistance
      exhibited by the regenerated seedlings.

PMID- 11233090
TI  - Development and characterization of salt tolerant somaclones in rice cultivar
      pokkali.
AB  - Primary regenerants (1190) of a tall traditional salt tolerant rice cultivar
      pokkali were produced through in vitro culture from mature seed derived calli of
      fourth subculture. Out of 35000 SC2 regenerants, 26 promising lines with superior
      agronomic traits were chosen initially for evaluation. SC3 and SC4 generations
      were stringently evaluated under hydroponics with excess salt stress as well as
      under field conditions across two growing seasons in Bay Islands. A set of 10
      promising somaclones was further evaluated at SC5 and SC6 of which BTS 2, BTS 13,
      BTS 18 and BTS 24 were found promising. In SC7 and SC8 yield trials in research
      farm, BTS 24 was found to produce a mean yield of 36.3 and 45.9 q ha-1 under
      saline and normal soil conditions, respectively. Somaclones varied significantly
      from the parent with respect to yield and yield attributes. Grain quality and
      biochemical parameters of all elite somaclones were different from the parent.
      However, somaclones did not deviate much from their parent in respect of disease
      and insect pest resistance pattern.

PMID- 11233092
TI  - Fungal metabolites from Aspergillus niger AN27 related to plant growth promotion.
AB  - Two metabolites have been isolated from Aspergillus niger AN27, a biocontrol
      agent, and identified as 2-carboxymethyl 3-n-hexyl maleic acid (compound 1) and 2
      methylene-3-hexylbutanedioic acid (compound 2). Their biological activities
      related to crop growth promotion have been assayed. Both the compounds increased
      germination and improved crop vigour. Compound 1 was more effective for increase
      in germination and shoot length, whereas compound 2 had relatively greater role
      in increasing the root length and biomass of cauliflower seedlings.

PMID- 11233091
TI  - Enhancement of polygalacturonase activity during auxin induced para nodulation
      and endorhizosphere colonization of Azospirillum in rice roots.
AB  - Effect of different auxins, namely, 2,4-dichlorophenoxyacetic acid (2,4-D),
      naphthalene acetic acid (NAA) and indole acetic acid (IAA) and Azospirillum
      brasilense bioinoculation on the enhancement of polygalacturonase (PG) activity
      in rice roots during para nodulation and endorhizosphere colonization of
      Azospirillum was studied under in vitro condition. It was observed that
      Azospirillum bioinoculation could augment PG activity of rice roots to a lesser
      extent without any root morphogenesis whereas auxin application together with
      Azospirillum bioinoculation enhanced PG activity of rice roots to a higher level
      which resulted in better root morphogenesis (para nodule) and endorhizosphere
      colonisation of A. brasilense. Among the three auxins tested, 2,4-D, even at
      lower concentration (0.5 ppm) enhanced the rice root PG activity, root
      morphogenesis and endorhizosphere colonization of Azospirillum while it was 2.0
      ppm with NAA and variable with IAA. It is concluded that there is a positive
      correlation existing among PG activity, degree of root morphogenesis and
      endorhizosphere colonization of Azospirillum brasilense in rice roots and the
      degree of correlation is determined by the chemical composition, concentration
      and mode of action of the auxin utilised.

PMID- 11233093
TI  - Neovascularisation offers a new perspective to glutamine related therapy.
AB  - Angiogenesis or the generation of new blood vessel, is an important factor in the
      growth of a solid tumor. Hence, it becomes a necessary parameter of any kind of
      therapeutic study. Glutamine is an essential nutrient of tumor tissue and
      glutamine related therapy involves clearance of circulatory glutamine by
      glutaminase. Therefore, using different murine solid tumor models, the present
      study was undertaken to find out whether the S-180 cell glutaminase has any
      effect on angiogenesis of solid tumor, or not. Result indicates that the purified
      S-180 cell glutaminase reduces tumor volume and restrict the generation of neo
      blood vessels. Therefore, it can be concluded that this enzyme may be an
      effective device against the cancer metastasis.

PMID- 11233094
TI  - Biochemical profile of erythrocyte membrane of jaundiced neonates.
AB  - Studies in newborn humans have demonstrated alteration in the lipid, phospholipid
      and cholesterol content when compared with age-matched control. Membrane bound
      (Na+ + K+)ATPase activity is found to be significantly increased in jaundiced
      neonates. Alteration in membrane permeability characteristics in jaundiced
      neonates causes severe microenvironmental changes in red blood cell profile.

PMID- 11233095
TI  - Methemoglobinemia in aluminium phosphide poisoning in rats.
AB  - Aluminium phosphide (AlP) a grain fumigant is the leading cause of intentional
      poisoning in North India. The mechanisms involved in toxicity are not known and
      there is no antidote till date. The present study was carried out to investigate
      the oxygen free radical generation, methemoglobinemia and effect of methylene
      blue treatment on survival time in rat model of AlP poisoning. AlP (50 mg/kg,
      intragastric) was administered in one group and the other group received AlP +
      Methylene Blue (MB) (0.1%, 1 mg/kg/5 min, i.v.). Malonyldialdehyde (MDA) and
      methemoglobin (MeHb) levels were measured at 10 and 30 min intervals. Blood MDA
      levels increased at 10 and 30 min after AlP exposure with simultaneous rise in
      MeHb levels suggesting methemoglobinemia could be due to increased oxygen free
      radical generation. Methylene blue caused a significant fall in both the
      parameters with prolongation of survival time. It is concluded that AlP causes
      methemoglobinemia responding to methylene blue treatment.

PMID- 11233096
TI  - Role of dopamine in the modulation of adrenal gland responses in the osmotically
      stressed pigeons, Columba livia.
AB  - Salt loading on pigeons (C. livia) had stimulatory effects on brain amines
      (dopamine and 5-hydroxytryptamine), corticosterone, norepinephrine and
      epinephrine contents of adrenal gland. Conjoint administration of dopamine with
      hypertonic saline restored the brain amines and corticosterone of adrenal gland,
      but had no effect on catecholamine (CAM) contents of adrenal medulla. The
      excessive release of CAM in the plasma indicates sympathetic stimulation after
      both the treatments.

PMID- 11233097
TI  - The effects of cations on the activity of the gypsy moth (Lepidoptera:
      Lymantriidae) nuclear polyhedrosis virus.
AB  - Fourteen cations were tested at a 1% concentration (wt:wt), as chlorides, for
      their effects on the biological activity of the gypsy moth, Lymantria dispar
      (L.), nuclear polyhedrosis virus (LdMNPV). Cupric chloride was toxic to gypsy
      moth larvae. Ferrous and ferric chloride were inhibitory to larval growth and
      development as well as to virus activity. Strontium chloride was inhibitory to
      virus activity but had no apparent effects on gypsy moth larvae. Six cations had
      little or no effect on virus activity (i.e., calcium, lanthanum, magnesium,
      nickel, potassium, sodium), whereas four cations (i.e., cobalt, manganese,
      ruthenium, zinc) acted as viral enhancers, as indicated by reductions in LC50s.

PMID- 11233098
TI  - Influence of western corn rootworm (Coleoptera: Chrysomelidae) larval injury on
      yield of different types of maize.
AB  - Two field experiments were conducted in 1995-1996 to determine if there are
      common yield responses among maize hybrids to larval western corn rootworm,
      Diabrotica virgifera virgifera LeConte injury. Three yellow dent hybrids, five
      white food grade dent hybrids, and a popcorn hybrid were included in the study.
      The minimum level of rootworm injury as measured by root damage ratings (3.2-4.2)
      that significantly reduced yield was similar across the hybrids included in the
      study. However, the pattern of yield response to different rootworm injury levels
      varied among hybrids. This suggests that maize hybrids may inherently differ in
      their ability to tolerate rootworm injury and partition biomass in response to
      injury and other stresses. The complex interaction among hybrid, level of injury,
      and other stresses suggests that a common western corn rootworm injury-yield
      relationship may not exist within maize.

PMID- 11233099
TI  - Effects of a broad spectrum and biorational insecticides on parasitoids of the
      Nantucket pine tip moth (Lepidoptera: Tortricidae).
AB  - We examined effects of aerial application of acephate (Orthene), Bacillus
      thuringiensis variety kurstaki Berliner (Foray), and tebufenozide (Mimic) on
      larval/pupal parasitoids of the Nantucket pine tip moth, Rhyacionia frustrana
      (Comstock), in the southwestern Georgia coastal plain. Parasitism of tip moths in
      acephate-treated plots was significantly lower than in untreated plots. Bacillus
      thuringiensis and tebufenozide showed no significant effects on parasitism. A
      tachinid, Lixophaga mediocris Aldrich, comprised a significantly greater
      proportion of emerging parasitoids in acephate-treated than in untreated control
      plots, whereas a chalcidid, Haltichella rhyacioniae Gahan, was less abundant in
      the acephate-treated plots. Acephate has a negative, but somewhat species
      specific, impact on tip moth parasitism.

PMID- 11233100
TI  - Potential effect of Anoplophora glabripennis (Coleoptera: Cerambycidae) on urban
      trees in the United States.
AB  - Anoplophora glabripennis Motschulsky, a wood borer native to Asia, was recently
      found in New York City and Chicago. In an attempt to eradicate these beetle
      populations, thousands of infested city trees have been removed. Field data from
      nine U.S. cities and national tree cover data were used to estimate the potential
      effects of A. glabripennis on urban resources through time. For the cities
      analyzed, the potential tree resources at risk to A. glabripennis attack based on
      host preferences, ranges from 12 to 61% of the city tree population, with an
      estimated value of $72 million-$2.3 billion per city. The corresponding canopy
      cover loss that would occur if all preferred host trees were killed ranges from
      13-68%. The estimated maximum potential national urban impact of A. glabripennis
      is a loss of 34.9% of total canopy cover, 30.3% tree mortality (1.2 billion
      trees) and value loss of $669 billion.

PMID- 11233101
TI  - Effects of an application of granular carbaryl on nontarget forest floor
      arthropods.
AB  - We evaluated the effects of a single application of granular carbaryl made
      against nymphal Ixodes scapularis Say on the diversity and abundance of forest
      arthropods taken in pitfall traps in oak and mixed oak-pine forest sites for 12
      wk after treatment in central New Jersey. Significant short-term changes in
      arthropod assemblages were detected immediately posttreatment. Effects were not
      distributed equally across taxa. Seasonal changes in numbers and diversity of
      forest arthropods in the study areas may have affected the impact of the
      acaricide in the treatment area. Comparison with control areas indicated that
      reductions in abundance of some arthropod taxa in the treatment area were
      detectable 12 wk after treatment.

PMID- 11233102
TI  - Azalea growth in response to azalea lace bug (Heteroptera: Tingidae) feeding.
AB  - The effects of azalea lace bug, Stephanitis pyrioides (Scott), feeding injury on
      azalea growth and development were investigated using 'Girard's Rose' azaleas
      during a 2-yr field study in Georgia Low, medium, and high injury treatments,
      which corresponded to 6, 8, and 14% maximum canopy area injury, were compared
      with control azaleas that received no lace bug infestation. Flower number, whole
      shrub leaf and stem dry mass, and dry mass and size of new growth tissues were
      unaffected by treatments. In contrast, growth index measurements, a general
      measure of variability frequently used for horticultural differentiation, showed
      significant reductions for all treatments in comparison to control azaleas after
      20 wk. Though not directly quantified, this apparent discrepancy may be explained
      as an artifact of lace bug feeding-induced leaf abscission. Growth index
      measurements had considerable variability and may not be the most reliable
      measurement of size. In July 1998, plant canopy densities among azaleas
      maintained in the high injury treatments were approximately 15% less full than
      the canopies of control shrubs. Predaceous insects had a significant negative
      association with azalea lace bug number during the 2-yr study. Flower and new
      tissue production, measured destructively during two growing seasons, revealed
      azalea tolerance to 14% of maximum canopy area lace bug feeding-injury levels.

PMID- 11233103
TI  - Seasonal capacity of attached and detached vineyard roots to support grape
      phylloxera (Homoptera: Phylloxeridae).
AB  - Field experiments were conducted to evaluate population densities and survival,
      developmental rate, and fecundity of grape phylloxera, Daktulosphaira vitifoliae
      (Fitch), as influenced by root attachment or detachment from mature, field-grown,
      Vitis vinifera L. grapevines through the growing season. Experiments were
      performed using artificial infestations of California biotype A grape phylloxera.
      Thirty-day bioassays on attached- and detached-roots were repeated monthly from
      May to September in 1997 (cultivar 'Carignane') and April to September in 1998
      (cultivar 'Thompson Seedless'). The bioassays showed that attached roots had
      lower population densities than detached roots in all months of both years.
      Densities varied by month, tending to be higher in spring than in summer. Of the
      population parameters studied, survival was most influenced by attachment
      condition, being higher on detached than on attached roots by up to 25-fold.
      These results imply the importance of vine-related mortality factors to grape
      phylloxera population density. Influence of root attachment condition on
      developmental rate and fecundity was not uniform across bioassay months for
      either year; however, in the four out of 21 assays where there was a significant
      difference it favored detached roots by twofold. Fruit harvest resulted in higher
      survival in the July assay but not for assays in August and September; however,
      neither developmental rate nor fecundity was affected by harvest in any ofthe
      assays. We conclude that mortality rather than nutritional factors are most
      limiting for field populations on susceptible vines. This work suggests that
      detachment of roots as occurs with root girdling by root pathogens may increase
      grape phylloxera populations on infested, susceptible vines. These results imply
      that excised root bioassays over-estimate grape phylloxera virulence and
      underestimate rootstock resistance.

PMID- 11233104
TI  - Comparison of Diadegma insulare (Hymenoptera: Ichneumonidae) and Microplitis
      plutellae (Hymenoptera: Braconidae) as biological control agents of Plutella
      xylostella (Lepidoptera: Plutellidae): field parasitism, insecticide
      susceptibility, and host-searching.
AB  - Parasitism of Plutella xylostella (L.) third and fourth instars was evaluated in
      a cabbage field in Geneva, NY, in 1999. Over the entire season, average
      parasitism was 33.6% for third instars and 53.6% for fourth instars, and the main
      parasitoids were Diadegma insulare (Cresson) and Microplitis plutellae Muesbeck.
      In the early season, total parasitism was low, and mainly caused by D. insulare.
      However, later in the season, parasitism reached >80% for the fouth instars and
      50% for the third instars. Our survey indicated that M. plutellae heavily
      parasitized P. xylostella, and provided higher parasitism rates than D. insulare
      in the late season. Comparison of these two species in laboratory bioassays
      indicated there were no significant differences in susceptibility to four
      insecticides commonly used in crucifer fields. For both parasitoids, an
      experience with P. xylostella on a damaged leaf increased their host-searching
      efficacy. Compared with M. plutellae, D. insulare was a better host-searcher both
      for the naive and the experienced adults. Although both parasitoids can cause
      high mortality rates of P. xylostella, D. insulare may be more suitable to be
      released in fields to enhance natural control against P. xylostella.

PMID- 11233105
TI  - Impact of four insecticides on Japanese beetle (Coleoptera: Scarabaeidae) egg
      predators and white grubs in turfgrass.
AB  - Field experiments were conducted to measure the effects of four commonly used
      turfgrass insecticides (isofenphos, diazinon, imidacloprid, halofenozide) on
      white grubs (Coleoptera: Scarabaeidae) and ant predators of white grub eggs. Ant
      populations were measured over time with canned tuna, whereas predation by the
      ants was measured with artificially placed Japanese beetle, Popillia japonica
      Newman, eggs. The effectiveness of each insecticide at controlling Japanese
      beetle grubs, when applied at different times during the growing season, also was
      measured. Isofenphos and diazinon significantly reduced both ant numbers and
      white grub egg predation, whereas imidacloprid and one halofenozide treatment did
      not significantly impact either measurement. A second halofenozide treatment
      significantly reduced white grub egg predation. Isofenphos and diazinon were
      ineffective at controlling Japanese beetle grubs when applied in June but were
      highly efficacious when applied in August. Evidence of enhanced biodegradation
      was found in plots that received both June and August applications of diazinon.
      Both June and August applications of imidacloprid and halofenozide provided good
      control of white grubs.

PMID- 11233106
TI  - Photoactive dye insecticide formulations: adjuvants increase toxicity to Mexican
      fruit fly (Diptera: Tephritidae).
AB  - The efficacy of photo active dyes as insecticides depends on the ingestion of the
      dye by the target insect and the activity of the dye at sensitive sites or on
      essential chemical functions. The site of this activity in insects is not
      understood, but we have found that certain chemical additives enhance the
      toxicity of phloxine B in the Mexican fruit fly. A series oftests with commercial
      adjuvants was performed under laboratory conditions that demonstrated a multifold
      decrease in the LD50 of phloxine B concentration and a decrease in the time
      required for photodynamic action to kill the flies. A total of 22 commercial
      adjuvants was tested. Of these, six were selected for evaluation under field cage
      conditions in comparison with a non-insecticide control bait (no treatment) and a
      phloxine B check bait with no adjuvant. Mortality was estimated by counting dead
      flies, feeding was estimated by fly counts at feeding stations, survival was
      estimated by trapping flies after the treatment period. In all cases the
      adjuvants increased the rate of mortality and decreased numbers surviving the
      treatment. Significant differences between adjuvants and both check and control
      were observed for mortality rates and the three best adjuvants, SM-9, Kinetic,
      and Tween60, induced significantly more mortality than the other adjuvants, the
      control, or the check. Feeding rates and survival rates indicated that the
      adjuvants increase the effectiveness of phloxine B in a predictable manner. The
      adjuvants appear to be active inside the insect rather than increasing the
      solubility of the dye in the bait medium. We propose that the addition of 1%
      vol:vol of the best adjuvant, Tween60 to the proteinaceous bait with 0.5%
      phloxine B will enhance toxicity as well as improve mixing and other
      characteristics of the bait.

PMID- 11233107
TI  - Toxicity of the herbicide glufosinate-ammonium to predatory insects and mites of
      Tetranychus urticae (Acari: Tetranychidae) under laboratory conditions.
AB  - The toxicities of the herbicide glufosinate-ammonium to three predatory insect
      and two predatory mite species of Tetranychus urticae Koch were determined in the
      laboratory by the direct contact application. At a concentration of 540 ppm (a
      field application rate for weed control in apple orchards), glufosinate-ammonium
      was almost nontoxic to eggs of Amblyseius womersleyi Schicha, Phytoseiulus
      persimilis Athias-Henriot, and T. urticae but highly toxic to nymphs and adults
      of these three mite species, indicating that a common mode of action between
      predatory and phytophagous mites might be involved. In tests with predatory
      insects using 540 ppm, glufosinate-ammonium revealed little or no harm to larvae
      and pupae of Chrysopa pallens Rambur but was slightly harmful to eggs (71.2%
      mortality), nymphs (65.0% mortality), and adults (57.7% mortality) of Orius
      strigicollis Poppius. The herbicide showed no direct effect on eggs and adults of
      Harmonia axyridis (Pallas) but was harmful, slightly harmful, and harmless to
      first instars (100% mortality), fourth instars (51.1% mortality), and pupae
      (24.5% mortality), respectively. The larvae and nymphs of predators died within
      12 h after treatment, suggesting that the larvicidal and nymphicidal action may
      be attributable to a direct effect rather than an inhibitory action of chitin
      synthesis. On the basis of our data, glufosinate-ammonium caused smaller effects
      on test predators than on T. urticae with the exception of P. persimilis,
      although the mechanism or cause of selectivity remains unknown. Glufosinate
      ammonium merits further study as a key component of integrated pest management.

PMID- 11233108
TI  - Resistance of temperate Chinese elms (Ulmus spp.) to feeding by the adult elm
      leaf beetle (Coleoptera: Chrysomelidae).
AB  - Newly acquired Ulmus species from the temperate regions of China growing at The
      Morton Arboretum, Lisle, IL, were evaluated in laboratory bioassays for feeding
      preference and suitability for larvae and adults of the elm leaf beetle,
      Pyrrhalta luteola (Muller). Larval and adult no-choice and adult multiple-choice
      feeding studies revealed that U changii, U. lanceaefolia, U. prunifolia, U.
      pseudopropinqua, and U. taihangshanensis were the least suitable for feeding and
      reproduction by the elm leaf beetle. Ulmus wallichiana and the highly preferred U
      pumila were more suitable for feeding and reproduction. Suitability had no
      significant effect on male and female longevity. The least suitable species of U.
      changii, U. lanceaefolia, U. prunifolia, U. pseudopropinqua, and U.
      taihangshanensis show promise for future elm breeding programs.

PMID- 11233109
TI  - Acaricidal properties of Artemisia absinthium and Tanacetum vulgare (Asteraceae)
      essential oils obtained by three methods of extraction.
AB  - Essential oils of Artemisia absinthium L. and Tanacetum vulgare L. were extracted
      by three methods, a microwave assisted process (MAP), distillation in water (DW)
      and direct steam distillation (DSD), and tested for their relative toxicity as
      contact acaricides to the two spotted spider mite, Tetranychus urticae Koch. All
      three extracts of A. absinthium and of T. vulgare were lethal to the spider mite
      but to variable degrees. The LC50 obtained from the DSD oil of A. absinthium was
      significantly lower (0.04 mg/cm2) than that of the MAP (0.13 mg/cm2) and DW (0.13
      mg/cm2) oil of this plant species. DSD and DW extracts of T. vulgare were more
      toxic (75.6 and 60.4% mite mortality, respectively, at 4% concentration) to the
      spider mite than the MAP extract (16.7% mite mortality at 4% concentration).
      Chromatographic analysis indicated differences in composition between the more
      toxic DSD oil of A. absinthium and the other two extracts of this plant,
      indicating that a sesquiterpene (C15H24) compound present in the DSD oil and
      absent in the other two may enhance the toxicity of the DSD oil. Chemical
      analysis of the T. vulgare extracts indicated that beta-thujone is by far the
      major compound of the oil (>87.6%) and probably contributes significantly to the
      acaricidal activity of the oil.

PMID- 11233110
TI  - Effect of bumble bee (Hymenoptera: Apidae) pollination intensity on the quality
      of greenhouse tomatoes.
AB  - Laboratory studies were conducted to assess tomato, Lycopersicon esculentum Mill.
      (Solanaceae), quality in relation to the level of buzz-pollination by bumble
      bees. Studies were conducted in commercial tomato greenhouses in the Leamington,
      Ontario, area to categorize bruising of tomato anther cones by bumble bees into
      five levels of bruising. The number of pollen grains per stigma was determined
      for each bruising level, and the bruising level was found to be a good predictor
      of stigmatic pollen load. Experimental flowers were pollinated by bumble bees and
      assigned to bruising levels based on the degree of anther cone discoloration.
      Fruit set, tomato weight, minimum diameter, the number of days until ripe,
      roundness, weight, percentage sugars, and number of seeds were assessed and
      compared among bruising level. Fruit set in flowers receiving no pollination
      visits was 30.2%, whereas, 83.3, 84.4, 81.2, and 100% of the flowers set fruit in
      bruising levels 1, 2, 3, and 4, respectively. Minimum diameter, number of seeds,
      and tomato weight all increased from no bruising to different levels of bruising.
      There was no increase in weight or diameter above a bruising level of 1, and no
      increase in the number of seeds per fruit after a bruising level of 2. We found
      that pollination of tomato flowers greater than a bruising level of 2
      (corresponding to approximately one to two bee visits) did not result in a
      significant increase in quality.

PMID- 11233111
TI  - Density-yield relationships and economic injury levels for Bemisia argentifolii
      (Homoptera: Aleyrodidae) in cantaloupe in Texas.
AB  - A range of infestation levels of the whitefly Bemisia argentifolii Bellows &
      Perring were established across experimental field plots of cantaloupe by varying
      insecticide treatments to evaluate the relationships between whitefly density and
      crop yield and quality. High levels of whitefly adults and immatures were
      associated with significant reductions in fruit yield, a decrease in fruit size,
      and an increase in the percentage of fruits with sooty mold. Yield loss rates
      (kg/ha/adult or nymph) decreased in a nonlinear fashion with increasing whitefly
      numbers. Estimated economic injury levels varied as a function of whitefly
      density, whitefly stage, control cost, crop cultivar, and crop season. Estimates
      of economic injury levels for one ($31.2/ha), five ($156/ha), and 10 ($312/ha)
      insecticide treatments ranged from 0.02 to 0.39, from 0.12 to 1.96, and from 0.24
      to 3.92 adults/leaf, and from 0.20 to 5.43, from 0.98 to 27.17, and from 1.97 to
      54.35 nymphs/6.45 cm2, respectively.

PMID- 11233112
TI  - Evaluation of action thresholds and spinosad for lepidopteran pest management in
      Minnesota cabbage.
AB  - Action thresholds, based on the percentage of plants infested, for the
      lepidopteran pest complex in fresh-market cabbage Brassica oleracea variety
      capitata were evaluated in 1996 and 1997 in southern Minnesota. Three
      lepidopteran pests are common in Minnesota, including the imported cabbageworm,
      Pieris (=Artogeia) rapae (L.), diamondback moth, Plutella xylostella (L.), and
      the cabbage looper, Trichoplusia ni (Hubner). Most of the thresholds tested
      included all three pests. However, because T. ni is often the most consistent and
      damaging pest in Minnesota, two thresholds were based solely on the percentage of
      plants infested with T. ni eggs and larvae. Action thresholds were also evaluated
      for their compatibility with a recently labeled biologically based insecticide,
      spinosad, and a conventional pyrethroid, permethrin. Although all three
      lepidopteran pests were present in both years of the study, P. rapae provided
      most of the pest pressure in 1996, and T. ni was most abundant in 1997. Compared
      with the 0% larval infestation treatment (approximately weekly sprays from early
      heading to harvest), all action thresholds resulted in less insecticide use (17-
      80%), while maintaining high levels of marketability. Despite variable pest
      pressure between years, one of the thresholds based solely on T. ni (10% of
      plants infested with eggs or larvae) performed as well as each of the thresholds
      based on all three species combined. For both years, and compared with a weekly
      spray schedule from early heading to harvest (average of 5.5 sprays per year),
      use of the 10% T. ni egg or larval threshold resulted in an average of 36.5% (3.5
      sprays) and 65% (2.0 sprays) fewer applications of spinosad and permethrin,
      respectively, with no significant loss in marketability. The results indicate
      that a variety of incidence-based action thresholds can be used to ensure the
      production of high-quality cabbage in the midwestern United States with only
      minimal applications of spinosad or permethrin.

PMID- 11233113
TI  - Field efficacy of sweet corn hybrids expressing a Bacillus thuringiensis toxin
      for management of Ostrinia nubilalis (Lepidoptera: Crambidae) and Helicoverpa zea
      (Lepidoptera: Noctuidae).
AB  - Field studies were done in 1995-1996 to assess the efficacy of three sweet corn
      hybrids that express the Bacillus thuringiensis (Bt) toxin, CrylAb, against two
      lepidopteran pests, Ostrinia nubilalis (Hubner) and Helicoverpa zea (Boddie). The
      Bt hybrids tested were developed by Novartis Seeds, using the event BT-11, which
      expresses Bt toxin in green tissue as well as reproductive tissues including the
      tassel, silk, and kernel. Bt hybrids were compared with a standard non-Bt control
      or the non-Bt isoline for each hybrid; none of the hybrids were treated with
      insecticides during the study. Hybrid efficacy was based on larval control of
      each pest, as well as plant or ear damage associated with each pest. In both
      years, control of O. nubilalis larvae in primary ears of all Bt hybrids was 99
      100% compared with the appropriate non-Bt check. Plant damage was also
      significantly reduced in all Bt hybrids. In 1996, control of H. zea in Bt hybrids
      ranged from 85 to 88% when compared with the appropriate non-Bt control. In 1996,
      a University of Minnesota experimental non-Bt hybrid (MN2 x MN3) performed as
      well as the Bt hybrids for control of O. nubilalis. Also, in 1996, two additional
      University of Minnesota experimental non-Bt hybrids (A684su X MN94 and MN2 X MN3)
      performed as well as Bt hybrids for percent marketable ears (ears with no damage
      or larvae). In addition, compared with the non-Bt hybrids, percent marketable
      ears were significantly higher for all Bt hybrids and in most cases ranged from
      98 to 100%. By comparison, percent marketable ears for the non-Bt hybrids
      averaged 45.5 and 37.4% in 1995 and 1996, respectively. Results from the 2-yr
      study strongly suggest that Bt sweet corn hybrids will provide high levels of
      larval control for growers in both fresh and processing markets. Specifically, Bt
      sweet corn hybrids, in the absence of conventional insecticide use, provided
      excellent control of O. nubilalis, and very good control of H. zea. However,
      depending on location of specific production regions, and the associated insect
      pests of sweet corn in each area, some insecticide applications may still be
      necessary.

PMID- 11233114
TI  - Portable trench barrier for protecting edges of tomato fields from Colorado
      potato beetle (Coleoptera: Chrysomelidae).
AB  - Experiments were conducted to test a portable trench barrier composed of an
      extruded, UV-retarded, PVC plastic trough, designed to allow Colorado potato
      beetles, Leptinotarsa decemlineata (Say), to enter and become trapped and killed
      inside. Tests demonstrated that the portable plastic trenches were effective as
      barriers to Colorado potato beetles as they walked into tomato, Lycopersicon
      esculentum Mill., fields from overwintering sites in the spring. In field tests,
      plots that were protected by portable trench barriers had significantly fewer
      beetles per tomato plant, and lower levels of defoliation. Tomato yields in plots
      that were protected by portable trench barriers were similar to yields in plots
      that were protected by insecticide sprays, and significantly higher than plots
      where beetles were not controlled.

PMID- 11233115
TI  - Evaluation of attractants for monitoring populations of the German cockroach
      (Dictyoptera: Blattellidae).
AB  - Lures that are used to attract German cockroaches, Blattella germanica (L.), to
      traps were compared in olfactometer assays in the laboratory and in trapping
      experiments in cockroach-infested homes and a swine farm. In olfactometer assays,
      AgriSense GP-2 was the most attractive lure, followed by peanut butter, and
      distiller's grain. Other lures, including Trapper tablet; Victor pheromone, a
      crude fecal extract that ostensibly contains B. germanica aggregation pheromone;
      and Victor food lure elicited upwind orientation from <50% of the test insects.
      Peanut butter and distiller's grain were equally attractive in trapping
      experiments in swine production barns and they captured significantly more
      cockroaches than the GP-2 tablet or the Victor pheromone lure; the commercial
      lures failed to attract significantly more cockroaches than the unbaited control
      traps. When tested against blank controls, cockroaches preferred to rest in
      shelters that contained the aggregation pheromone-based lure (Victor), but this
      lure was the least attractive to cockroaches in olfactometer assays. These
      results do not support claims that commercial crude fecal extracts attract
      cockroaches to traps, and they highlight a need for developing more attractive
      lures for detection of cockroaches and for monitoring populations.

PMID- 11233116
TI  - Positive effects of some gyrase inhibitors on survival and development of Pimpla
      turionellae (Hymenoptera: Ichneumonidae) larvae reared on an artificial diet.
AB  - Effects of novobiocin, nalidixic, and oxolinic acids on the survival and
      development of the hymenopterous endoparasitoid Pimpla turionellae L. were
      investigated alone and in various combinations by rearing larvae aseptically on
      chemically defined synthetic diets. Effects varied with the levels and kinds of
      the antibiotics in the tested combinations. Among the tested antibiotics alone,
      only the lowest level of novobiocin enhanced the postlarval survival. Most of the
      combinations significantly increased the number of survivors in the postlarval
      developmental stages. Novobiocin in combination with nalidixic acid (6.0:2.0 mg)
      in the artificial diet produced a yield of 80.8% pupae and 69.4% adults,
      respectively. This combination also shortened the developmental time to adult
      emergence. Similarly, on most of the diets with combinations of the antibiotics,
      the development of the larvae up to adult stage was noticeably faster than those
      on the control diets. An approximately equals 50% reduction in the percentages of
      pupae and adults was recorded by 6.0 mg of novobiocin in combination with 0.75 mg
      of oxolinic acid compared with the control diet. Although this combination
      prolonged the complete development of the insect according to other novobiocin
      and oxolinic acid combinations, developmental time was significantly shorter than
      that with control diet.

PMID- 11233117
TI  - Transfer of toxicants from exposed nymphs of the drywood termite Incisitermes
      snyderi (Isoptera: Kalotermitidae) to unexposed nestmates.
AB  - Two formulations of spinosad (NAF-85 and NAF-371) were evaluated to determine the
      effect of concentration, deposit condition (dried, wet, or topical), and exposure
      time (0.1-10 h) for toxicant transfer among nestmates in the drywood termite
      Incisitermes snyderi (Light). Spinosad treatments were compared with two
      formulations of disodium octaborate tetrahydrate (DOT) (10% aqueous dilution, 98%
      dust) and with 35% calcium arsenate dust. Termites were dyed and individually
      exposed to different treatments for 0.1, 1.5,1.0, 5.0, 10.0 h, or 0.1 and 1.0 h
      (DOT and calcium arsenate dust) and then placed with 10 unmarked, untreated
      nestmates in a petri dish. Spinosad formulations also were evaluated by topical
      application to dyed termites. Transfer of lethal doses of toxicants between
      termites was indicated by significant mortality of untreated termites in 25 of 28
      treatments by 28 d after introduction of dyed, treated termites. Only three
      treatments, one spinosad treatment (NAF-371, wet, 1 h) and both DOT 10% solution
      treatments, resulted in mortality of untreated termites that was not
      significantly different than that of water-treated controls. Two spinosad
      treatments and both calcium arsenate dust treatments resulted in >90% (94-98%)
      mortality of untreated termites by 28 d after introduction. Mortality of
      untreated termites was significantly different from controls for the two spinosad
      formulations, depending on condition of deposit and duration of dyed termite
      exposure to treatments.

PMID- 11233118
TI  - Genetic variation and correlations among responses to five insecticides within
      natural populations of Drosophila melanogaster (Diptera: Drosophilidae).
AB  - To investigate the genetic basis of cross-resistance to insecticides, natural
      populations of Drosophila melanogaster (Meigen) were first collected from four
      different locations in Japan. After 10-80 isofemale lines of each population had
      been established in a laboratory, the susceptibility of each line to each of the
      insecticides permethrin, malathion, fenitrothion, prothiophos, and DDT was
      examined. Broad ranges of continuous variation in susceptibility to all the
      chemicals were observed within each natural population as a whole. In addition,
      highly significant correlations among responses to organophosphates were
      observed. However, based on the coefficients of determination, about less than
      half of variation in responses to one insecticide could be explained by variation
      in responses to another insecticide, suggesting that not only a common resistance
      factor but also other factors could be involved in a natural population. Genetic
      analyses by using resistant and susceptible inbred lines from the same natural
      population demonstrated that resistance to organophosphates in some resistant
      lines could be due to a single or tightly linked factors, and that resistance in
      the other line may be due to more than one major factor. These observations could
      suggest that several resistance factors may be involved within each natural
      population, and that some of major factors could contribute to correlations among
      responses to organophosphates. These major factors could then contribute to the
      broad ranges of continuous variation observed at the level of the populations.

PMID- 11233119
TI  - Susceptibility of male oriental fruit moth (Lepidoptera: Tortricidae) populations
      from New Jersey apple orchards to azinphosmethyl.
AB  - Toxicological responses to azinphosmethyl of male Oriental fruit moth, Grapholita
      molesta (Busck), from five commercial orchards in which control failures had
      occurred were examined for azinphosmethyl resistance and for potential resistance
      mechanisms by using topical pheromone trap bioassay and compared with a reference
      population that had no history of control failure and had received little
      selection pressure. The 1998 field survey indicated moderate level of resistance
      to azinphosmethyl (2.7-4.1-fold); slopes of regressions lines (2.47-2.76)
      indicate genetically heterogeneous populations. An approximate twofold decline
      was observed between the fourth flight of 1998 and the first flight of 1999,
      suggesting the presence of unstable resistance in moths collected from these
      study sites. The 1999 field surveys indicated lower levels of tolerance to
      azinphosmethyl. The resistance ratios ranged from 1.17 to 1.86 during the first
      flight of 1999 and 1.24-2.64 during the fourth flight of 1999. Steep slopes of
      the concentration-response lines during 1999 season indicated the presence of
      genetically homogeneous populations with some exceptions. A 1.5-2.0-fold increase
      was observed between the first and fourth flights of 1999, indicating that
      resistance can build up during the growing season. S,S,S,-tri-n-butyl
      phosphorotrithioate (DEF), but not piperonyl butoxide, significantly enhanced the
      toxicity of azinphosmethyl, suggesting that enhanced metabolism by esterases is
      involved in the tolerance of azinphosmethyl in moths collected from these study
      sties.

PMID- 11233120
TI  - Greenhouse tests on resistance management of Bt transgenic plants using refuge
      strategies.
AB  - Experimental evaluation of the effectiveness of resistance management tactics is
      vital to help provide guidelines for the deployment of transgenic insecticidal
      crops. Transgenic broccoli expressing a Cry1Ac gene of Bacillus thuringiensis
      (Bt) and the diamondback moth, Plutella xylostella (L.), were used in greenhouse
      tests to evaluate the influence of size and placement of nontransgenic refuge
      plants on changes in resistance allele frequency and pest population growth. In
      the first test with an initial Cry1Ac-resistance (R) allele frequency of 0.007,
      P. xylostella were introduced into cages with the following treatments: 0, 3.3,
      10, 20, and 100% refuge plants. Results after four generations showed that
      resistance could be delayed by increasing the proportion of refuge plants in the
      cage. Population growth was also influenced by refuge size with the highest
      populations occurring in treatments that had either no refuge plants or all
      refuge plants. In the second test, we evaluated the effect of refuge placement by
      comparing 20% separate and 20% mixed refuges. P. xylostella with an initial
      frequency of resistant alleles at 0.0125 were introduced into cages and allowed
      to cycle; later generations were evaluated for resistance and population growth.
      Separating the refuge had a pronounced effect on delaying resistance and slowing
      establishment of resistant larvae on Bt plants. Combining information from both
      trials, we found a strong negative correlation between the number of larvae on Bt
      plants and the mortality of the population in leaf dip bioassays. Results from
      larval movement studies showed that separate refuges delayed resistance better
      than mixed refuges because they conserved relatively more susceptible alleles
      than R alleles and did not increase the effective dominance of resistance.

PMID- 11233121
TI  - Genetics of pink bollworm resistance to Bacillus thuringiensis toxin Cry1Ac.
AB  - Laboratory selection increased resistance of pink bollworm (Pectinophora
      gossypiella) to the Bacillus thuringiensis toxin Cry1Ac. Three selections with
      Cry1Ac in artificial diet increased resistance from a low level to >100-fold
      relative to a susceptible strain. We used artificial diet bioassays to test F1
      hybrid progeny from reciprocal crosses between resistant and susceptible strains.
      The similarity between F1 progeny from the two reciprocal crosses indicates
      autosomal inheritance of resistance. The dominance of resistance to Cry1Ac
      depended on the concentration. Resistance was codominant at a low concentration
      of Cry1Ac, partially recessive at an intermediate concentration, and completely
      recessive at a high concentration. Comparison of the artificial diet results with
      previously reported results from greenhouse bioassays shows that the high
      concentration of Cry1Ac in bolls of transgenic cotton is essential for achieving
      functionally recessive inheritance of resistance.

PMID- 11233122
TI  - Pyrethroid resistance and mechanisms of resistance in field strains of
      Helicoverpa armigera (Lepidoptera: Noctuidae).
AB  - Pyrethroid resistance was found in 54 field strains of Helicoverpa armigera
      collected between 1995 and 1999 from 23 districts in seven states of India. LD50
      values of the field strains ranged from 0.06 to 72.2 microg/larva with slopes of
      0.5-3.1. Resistance was highest in regions where pyrethroid use was frequent
      (four to eight applications per season). Resistance to deltamethrin was
      exceptionally high with resistance ratios of 13,570 and 27,160 in two strains
      collected during February 1998 in central India. Resistance to cypermethrin,
      fenvalerate and cyhalothrin also was high with resistance ratios of >1,000 in
      four strains collected from central and southern India. Resistance ratios were
      below 100 in >50% of the strains tested. Pyrethroid resistance was high in
      strains collected from the districts in Andhra Pradesh where a majority of the
      cotton farmer suicide cases in India were reported. Resistance to pyrethroids
      appeared to have increased over 1995-1998 in most of the areas surveyed. Studies
      carried out through estimation of detoxification enzyme activity and synergists
      indicated that enhanced cytochrome p450 and esterase activities were probably
      important mechanisms for pyrethroid resistance in field strains. Pyrethroid nerve
      insensitivity also was found to be a major mechanism in some parts of the country
      where the use of pyrethroids was high. The information presented illustrates the
      importance of proper insect management programs to avoid the consequences
      associated with improper insecticide use.

PMID- 11233123
TI  - Baseline monitoring of codling moth (Lepidoptera: Tortricidae) larval response to
      benzoylhydrazine insecticides.
AB  - A diet-incorporation larval bioassay was developed to measure the response of
      codling moth, Cydia pomonella (L.), to the benzoylhydrazine insecticides
      tebufenozide and methoxyfenozide. The bioassay tested neonates and third, fourth,
      and fifth instars from a laboratory colony and neonates and fourth instars from a
      pooled population collected from five certified-organic apple orchards. Bioassays
      were scored after 6 and 14 d. No differences between the laboratory and field
      population were found for either insecticide. Significant differences were found
      in the response of third and fifth instars between the 6 and 14 d bioassays,
      primarily due to a high proportion of moribund larvae in the shorter assay.
      Larval age had a significant effect in bioassays and was more pronounced in 6-
      versus 14-d tests. Fifth instars were significantly less susceptible to both
      insecticides than other stages, while responses of third and fourth instars were
      similar. The response of neonates was significantly different from third and
      fourth instars to tebufenozide but not with methoxyfenozide in the 14-d test.
      Field bioassays excluded the use of fifth instars and were scored after 14 d.
      LC50s estimated for 18 field-collected populations varied five- and ninefold for
      tebufenozide and methoxyfenozide, respectively. The responses of all but six
      field-collected populations were significantly different from the laboratory
      strain. Five of these six populations were collected from orchards with no
      history of organophosphate insecticide use. The LC50 for methoxyfenozide of one
      field-collected population reared in the laboratory for three generations
      declined fourfold, but was still significantly different from the laboratory
      population. These data suggest that transforming current codling moth management
      programs in Washington from a reliance on organophosphate insecticides to
      benzoylhydrazines may be difficult.

PMID- 11233124
TI  - Effect of nitrogen fertilization on Aphis gossypii (Homoptera: Aphididae):
      variation in size, color, and reproduction.
AB  - The effect of nitrogen fertilization on Aphis gossypii Glover color and size,
      fertility, and intrinsic rate of increase (rm) was studied on cotton plants.
      Nitrogen fertilization treatments consisted of 0, 50, 100, and 150% of the
      agronomic recommended level. Adult and nymph densities, as well as rm, were
      positively correlated with nitrogen fertilization. Aphid body length, head width,
      and darkness of color were recorded in populations on cotton plants fertilized
      with 100% nitrogen or with no nitrogen fertilization. Aphids on nitrogen
      fertilized plants were significantly bigger and darker. All body size and
      darkness of color measurements were positively correlated with aphid fecundity.
      It was also found that the nutritional quality of the host plant on which the
      parent generation feeds has a stronger effect on the aphids than that of the
      quality of their own food plants. This phenomenon may dampen the effect short
      term fluctuations in host plant quality have on aphid performance. Results are
      discussed in the context of aphid population biology, aphid-plant interactions
      and aphid population management.

PMID- 11233125
TI  - Field evaluation of resistance of transgenic rice containing a synthetic cry1Ab
      gene from Bacillus thuringiensis Berliner to two stem borers.
AB  - Two transgenic rice (Oryza sativa L.) lines, KMD1 and KMD2 at the R4 generation,
      transformed with a synthetic cry1Ab gene from Bacillus thuringiensis Berliner,
      were first evaluated for stem borer resistance in the field during the rice
      growing season of 1998 in two areas of Zhejiang Province, China. Both KMD1 and
      KMD2 were highly resistant to the stem borers Chilo suppressalis (Walker) and
      Scirpophaga incertulas (Walker), and were completely undamaged during the whole
      rice growing season. In contrast, damage to the plants of the untransformed
      parental control (Xiushui 11) was in the form of deadhearts or whiteheads. Under
      natural infestation by the C. suppressalis, the damage to control plants reached
      a peak of 88.7% of plants and 20.1% of tillers encountered with deadhearts. Under
      artificial and natural infestation of neonate striped stem borers at the
      vegetative stage and booting stage, 100% of plants and 25.6% of tillers, 78.9% of
      plants and 15.6% of productive tillers among artificially infested control plants
      were observed with the symptom of deadhearts and whiteheads, respectively. Damage
      to the control plants from artificial infestation by the S. incertulas reached a
      peak of 97.0% of plants and 22.9% of tillers damaged. The field research
      indicated that both KMD1 and KMD2 show great potential for protecting rice from
      attack by these two stem borers.

PMID- 11233126
TI  - Inheritance of resistance to ear damage caused by Sesamia nonagrioides
      (Lepidoptera: Noctuidae) in maize.
AB  - Sesamia nonagrioides Lefebvre is a major insect pest of maize (Zea mays L.) in
      northwestern Spain. The inheritance of ear resistance in field corn to this pest
      has not been studied. This work aims to determine the importance of genetic
      (additive, dominance, and epistatic effects) and environmental effects in the
      inheritance of ear resistance to S. nonagrioides. Three field corn inbreds
      (CM109, EP31, and EP42) were used as parents and two crosses (CM109 x EP31 and
      CM109 x EP42) were made. These inbreds show different ear resistance levels to S.
      nonagrioides, with CM109 more resistant than EP31 and EP42. For each cross,
      parents (P1, P2), F1, F2, and backcrosses to each parent (BC1 and BC2) were
      evaluated. Correlations among ear damage traits showed that general appearance of
      the ear should be useful indicator of ear resistance. Ear resistance was dominant
      to susceptibility and was transmitted from inbreds to their hybrids. The additive
      dominance model fit the generation mean analysis for both crosses and the degree
      of genetic control varied depending on the cross and trait. For both crosses,
      additive and dominance effects were significant for most ear damage traits.
      Epistatic gene effects were significant for husk and shank damage, and gene
      effects for number and length of tunnels were not significant. Because ear
      resistance involved additive and dominance effects for this set of inbreds,
      breeding procedures based on both types of gene action should be effective.

PMID- 11233127
TI  - Correlating differences in larval survival and development of bollworm
      (Lepidoptera: Noctuidae) and fall armyworm (Lepidoptera: Noctuidae) to
      differential expression of Cry1A(c) delta-endotoxin in various plant parts among
      commercial cultivars of transgenic Bacillus thuringiensis cotton.
AB  - Differences in larval survival and development of bollworm, Helicoverpa zea
      (Boddie), and fall armyworm, Spodoptera frugiperda (J. E. Smith), respectively,
      were found to exist among commercially available Cry1A(c) transgenic Bacillus
      thuringiensis Berliner (Bt) varieties. Using a quantification assay (ELISA) to
      measure the levels of delta-endotoxin in two of these varieties ('DP 451B/RR' and
      'NuCOTN 33B'), differences in the amount of delta-endotoxin present in various
      plant parts was correlated with larval survival of bollworms and larval
      development of fall armyworms throughout the growing season. Larvae that were fed
      on DP 451B/RR completed development faster and exhibited better survivorship than
      those larvae fed NuCOTN 33B, whereas lower levels of delta-endotoxin were
      generally detected in plant parts from DP 451B/RR compared with NuCOTN 33B. These
      differences may impact population dynamics of these pests which may be a critical
      factor in managing resistance to Bt. Furthermore, the utility of using this
      system for providing information to the grower concerning varietal choices may be
      more common in the future.

PMID- 11233128
TI  - Seasonal movement and distribution of the grape mealybug (Homoptera:
      Pseudococcidae): developing a sample program for San Joaquin Valley vineyards.
AB  - The grape mealybug, Pseudococcus maritimus (Ehrhorn), is an important pest of
      table grapes in California's San Joaquin Valley. The mealybug causes direct
      damage by infesting grape bunches, resulting in very low economic injury levels.
      To develop a sampling program to help growers predict damage and make control
      decisions, we destructively sampled six entire grapevines each month to determine
      mealybug abundance and within-vine distribution. These absolute counts were then
      used to evaluate several relative sampling methods: sticky tape barriers on
      canes, excised spur samples, standard-sized pieces of bark, timed counts, and
      nondestructive counts on spurs. At midseason we sampled additional vines to
      correlate mealybug numbers with economic damage at harvest. Finally, mealybug
      life stages and natural enemies were recorded throughout the study. Timed 5-min
      counts show the strongest correlation with total mealybug numbers, and a simple
      count of mealybugs on three spurs per vine at midseason is the best predictor of
      economic damage. Mealybugs completed approximately equals 2.5 generations in
      1998. Comparison to data on mealybug development suggests that exceptionally long
      growing seasons could exacerbate infestations by allowing the completion of a
      third generation. No mealybugs were found on bunches before early August, when
      second-generation crawlers moved out of the bark. Grape bunches that touched old
      wood had significantly higher damage and mealybug densities. The majority of
      mealybugs were always found in protected locations (under the bark of the trunk,
      spurs or canes), indicating the need for chemical or biological controls that can
      penetrate these refugia.

PMID- 11233129
TI  - Quarantine security of bananas at harvest maturity against Mediterranean and
      Oriental fruit flies (Diptera: Tephritidae) in Hawaii.
AB  - Culled bananas (dwarf 'Brazilian', 'Grand Nain', 'Valery', and 'Williams')
      sampled from packing houses on the islands of Hawaii, Kauai, Maui, Molokai, and
      Oahu identified specific "faults" that were at risk from oriental fruit fly,
      Bactrocera dorsalis (Hendel), infestation. Faults at risk included bunches with
      precociously ripened bananas, or bananas with tip rot, fused fingers, or damage
      that compromised skin integrity to permit fruit fly oviposition into fruit flesh.
      No Mediterranean fruit fly, Ceratitis capitata (Wiedemann), or melon fly, B.
      cucurbitae (Coquillett), infestations were found in culled banana samples. Field
      infestation tests indicated that mature green bananas were not susceptible to
      fruit fly infestation for up to 1 wk past the scheduled harvest date when
      attached to the plant or within 24 h after harvest. Recommendations for exporting
      mature green bananas from Hawaii without risk of fruit fly infestation are
      provided. The research reported herein resulted in a USDA-APHIS protocol for
      exporting mature green bananas from Hawaii.

PMID- 11233130
TI  - Influence of timing and prey availability on fruit damage to apple by Campylomma
      verbasci (Hemiptera: Miridae).
AB  - Campylomma verbasci Meyer is a zoophytophagous mirid that feeds on small
      arthropods as well as apple (Malus domestica Borkhausen) fruits, causing economic
      damage to some cultivars. The influence of timing and prey availability on the
      amount of fruit damage was studied to determine whether either factor could be
      used to refine a management program. C. verbasci nymphs were caged on branches of
      fruiting 'Golden Delicious' apple trees during the period from bloom through
      early fruit set. The greatest amount of fruit damage occurred during the bloom
      period; little or no damage occurred after fruit reached approximately equals 13
      mm in diameter. The availability of prey did not reduce the incidence of fruit
      damage by C. verbasci, nor did it influence the survival of nymphs. Nymphal
      survival was higher, however, in cages where a blossom or fruitlet was present
      versus a vegetative spur. These data support the hypothesis that post petal fall
      insecticide applications (those made after the fruit is greater than
      approximately equals 10-13 mm in diameter) are not useful in preventing economic
      levels of fruit damage in Washington State, and that petal fall applications
      would only prevent a fraction of the total amount of damage by this pest. The
      data from this study do not support the hypothesis that manipulating arthropod
      prey species of C. verbasci will prevent fruit damage. There was evidence to
      support the hypothesis that nymphs can survive a relatively short period (7 d)
      without arthropod prey.

PMID- 11233131
TI  - Enhancement of attraction of alpha-ionol to male Bactrocera latifrons (Diptera:
      Tephritidae) by addition of a synergist, cade oil.
AB  - Male lures are known for many tephritid fruit fly species and are often preferred
      over food bait based traps for detection trapping because of their high
      specificity and ability to attract flies over a wide area. Alpha-ionol has been
      identified as a male lure for the tephritid fruit fly Bactrocera latifrons
      (Hendel). The attraction of this compound to male B. latifrons individuals,
      however, is not as strong as is the attraction of other tephritid fruit fly
      species to their respective male lures. Cade oil, an essential oil produced by
      destructive distillation of juniper (Juniperus oxycedrus L.) twigs, synergizes
      the attraction of alpha-ionol to male B. latifrons. Catches of male B. latifrons
      at traps baited with a mixture of alpha-ionol and cade oil were more than three
      times greater than at traps baited with alpha-ionol alone. Substitution of alpha
      ionol + cade oil for alpha-ionol alone in detection programs could considerably
      improve the chance of detecting invading or incipient populations of B.
      latifrons. However, detection programs should not rely solely on this lure but
      also make use of protein baited traps as well as fruit collections. Further work
      with fractions of cade oil may help to identify the active ingredient(s), which
      could help to further improve this male lure for B. latifrons.

PMID- 11233132
TI  - Efficacy of CC traps and seasonal activity of adult Bemisia argentifolii
      (Homoptera: Aleyrodidae) in Imperial and Palo Verde Valleys, California.
AB  - Adult whitefly Bemisia argentifolii Bellows & Perring trap (CC trap) catches were
      compared with suction type trap catches. CC trap catches were significantly
      correlated to the suction trap catches. Higher numbers of B. argentifolii adults
      were caught in CC traps oriented toward an untreated, B. argentifolii-infested,
      cotton field as compared with traps oriented toward Bermuda grass fields, farm
      roads, or fallow areas. CC trap catches at five heights above ground (from 0 to
      120 cm) were significantly related to each other in choice and no-choice studies.
      CC trap catches were low in the Imperial and Palo Verde Valleys from late October
      to early June each of 1996, 1997, and 1998. Trap catches increased with
      increasing seasonal air temperatures and host availability. Trap catches were
      adversely affected by wind and rain. Abrupt trap catch increases of 40- to 50
      fold for 1-2 d in late June to early July followed by abrupt decreases in adult
      catches suggest migrating activity of adults from other nearby crop sources.

PMID- 11233133
TI  - Lethal and sublethal effects of insecticide residues on Orius insidiosus
      (Hemiptera: Anthocoridae) and Geocoris punctipes (Hemiptera: Lygaeidae).
AB  - Laboratory-reared predators, the insidious flower bug, Orius insidiosus (Say),
      and big-eyed bug Geocoris punctipes (Say), were exposed to 10 insecticides,
      including three newer insecticides with novel modes of action, using a residual
      insecticide bioassay. These species are important predators of several economic
      pests of cotton. Insecticides tested were: azinphos-methyl, imidacloprid,
      spinosad, tebufenozide, fipronil, endosulfan, chlorfenapyr, cyfluthrin,
      profenofos, and malathion. There was considerable variation in response between
      both species tested to the insecticides. Tebufenozide and cyfluthrin were
      significantly less toxic to male O. insidiosus than malathion. Tebufenozide was
      also significantly less toxic to female O. insidiosus than malathion.
      Imidacloprid, tebufenozide, and spinosad were significantly less toxic to male G.
      punctipes than chlorfenapyr, endosulfan, and fipronil. Spinosad, tebufenozide,
      and azinphos-methyl were significantly less toxic to female G. punctipes than
      fipronil and endosulfan. Fecundity of O. insidiosus was significantly greater in
      the spinosad treatment compared with other treatments including the control.
      Consumption of bollworm, Helicoverpa zea (Boddie), eggs by O. insidiosus was
      significantly lower in the fipronil, profenofos, and cyfluthrin treatments
      compared with other treatments including the control. Consumption of H. zea eggs
      by G. punctipes was significantly lower in the malathion, profenofos, endosulfan,
      fipronil, azinphos-methyl, and imidacloprid treatments compared with the control.
      Egg consumption by G. punctipes was not significantly different in the
      tebufenozide treatment compared with the control. The lower toxicity of spinosad
      to G. punctipes is consistent with other reports. Based on these results, the
      following insecticides are not compatible with integrated pest management of
      cotton pests: malathion, endosulfan, profenofos, fipronil, and cyfluthrin; while
      imidacloprid, tebufenozide, azinphos-methyl, and spinosad should provide pest
      control while sparing beneficial species.

PMID- 11233134
TI  - Lethal and sublethal effects of bendiocarb, halofenozide, and imidacloprid on
      Harpalus pennsylvanicus (Coleoptera: Carabidae) following different modes of
      exposure in turfgrass.
AB  - Routes by which nontarget predatory insects can be exposed to turfgrass
      pesticides include topical, residual, and dietary exposure. We used each of these
      routes to evaluate potential lethal or sublethal effects of two novel turfgrass
      insecticides, imidacloprid and halofenozide, and a carbamate, bendiocarb, on
      survival, behavior, and fecundity of the ground beetle Harpalus pennsylvanicus
      DeGeer. Field-collected carabids were exposed to direct spray applications in
      turf plots, fed food contaminated by such applications, or exposed to irrigated
      or nonirrigated residues on turf cores. Halofenozide caused no apparent acute,
      adverse effects through topical, residual, or dietary exposure. Moreover, the
      viability of eggs laid by females fed halofenozide-treated food once, or
      continuously for 30 d, was not reduced. In contrast, topical or dietary exposure
      of carabids to bendiocarb inevitably was lethal. Exposure to imidacloprid by
      those routes caused high incidence of sublethal, neurotoxic effects including
      paralysis, impaired walking, and excessive grooming. Intoxicated beetles usually
      recovered within a few days in the laboratory, but in the field, they were shown
      to be highly vulnerable to predation by ants. One-time intoxication by
      imidacloprid did not reduce females' fecundity or viability of eggs. There was no
      apparent behavioral avoidance of insecticide residues, or of insecticide-treated
      food. Carabids exposed to dry residues on turfgrass cores suffered high mortality
      from bendiocarb, and some intoxication from imidacloprid, but these effects were
      greatly reduced by posttreatment irrigation. Implications for predicting hazards
      of insecticides to beneficial invertebrates in turfgrass are discussed.

PMID- 11233135
TI  - Spider fauna in apple ecosystem of western Oregon and its field susceptibility to
      chemical and microbial insecticides.
AB  - Twelve families, 26 genera, and 30 identifiable spider species were found in
      surveys conducted in apple orchards of western Oregon. The Salticidae,
      Linyphiidae, Clubionidae, Philodromidae, and Theridiidae comprised 85.56% ofthe
      total spiders collected. The most common species in order of abundance were
      Metaphidippus aeneolus Curtis, Spirembolus mundus Chamberlin & Ivie,
      Cheiracanthium inclusum (Hentz), Philodromus spectabilis Keyserling, Eris
      marginata (Walckenaer), and Theridion lawrencei Gertsch & Archer. Individuals of
      these species were collected in 50-60% of the samples and were most abundant in
      the month of August. The Bacillus thuringiensis-based insecticides, DiPel (100
      Million International Units/100 liters) and MVP (250 ml/100 liters), summer oil
      (0.5-1.0 liter/100 liters), the insect growth regulator (IGR) diflubenzuron (3-12
      g/100 liters), and organophosphate Phosmet (6-60 g/100 liters) were generally
      harmless (P > 0.05) to these spider species. Full field rates of organophosphate
      azinphosmethyl (25 g/100 liters) and carbamate carbaryl (60 g/100 liters) were
      slightly to moderately harmful (25-75% mortality). These insecticides at reduced
      rates (azinphosmethyl 2.5-5.0 g and carbaryl 12 g/100 liters) applied alone or in
      combination with DiPel and MVP, had a negligible effect. Full rates of
      pyrethroids esfenvalerate (2.5 g/100 liters) and permethrin (4.0 g/100 liters)
      were moderately to highly harmful (50-75% mortality) and their reduced rates
      (esfenvalerate 0.25-0.50 g and permethrin 0.4-0.8 g/100 liters) were selective to
      the spiders.

PMID- 11233136
TI  - Virulence of entomopathogenic nematodes to pecan weevil larvae, Curculio caryae
      (Coleoptera: Curculionidae), in the laboratory.
AB  - The pecan weevil, Curculio caryae (Horn), is a key pest of pecans in the
      Southeast. Entomopathogenic nematodes have been shown to be pathogenic toward the
      larval stage of this pest. Before this research, only three species of nematodes
      had been tested against pecan weevil larvae. In this study, the virulence of the
      following nine species and 15 strains of nematodes toward fourth-instar pecan
      weevil was tested: Heterorhabditis bacteriophora Poinar (Baine, HP88, Oswego,
      NJ1, and Tf strains), H. indica Poinar, Karunakar & David (original and Homl
      strains), H. marelatus Liu & Berry (IN and Point Reyes strains), H. megidis
      Poinar, Jackson & Klein (UK211 strain), H. zealandica Poinar (NZH3 strain),
      Steinernema riobrave Cabanillas, Poinar & Raulston (355 strain), S. carpocapsae
      (Weiser) (All strain), S. feltiae (Filipjev) (SN strain), and S. glaseri
      (Steiner) (NJ43 strain). No significant difference in virulence was detected
      among nematode species or strains. Nematode-induced mortality was not
      significantly greater than control mortality (in any of the experiments
      conducted) for the following nematodes: H. bacteriophora (Baine), H. zealandica
      (NZH3), S. carpocapsae (All), S. feltiae (SN), S. glaseri (NJ43), and S. riobrave
      (355). All other nematodes caused greater mortality than the control in at least
      one experiment. Heterorhabditis megidis (UK211) but not H. indica (original)
      displayed a positive linear relationship between nematode concentration and
      larval mortality. Results suggested that, as pecan weevil larvae age, they may
      have become more resistant to infection with entomopathogenic nematodes.

PMID- 11233137
TI  - Species diagnosis and Bacillus thuringiensis resistance monitoring of Heliothis
      virescens and Helicoverpa zea (Lepidoptera: Noctuidae) field strains from the
      southern United States using feeding disruption bioassays.
AB  - Validation of a feeding disruption bioassay for the detection of resistance to
      Bacillus thuringiensis toxin and species identification is reported using field
      strains of Heliothis virescens and Helicoverpa zea collected from the southern
      United States in 1998. Feeding disruption is measured by a lack of fecal
      production from larvae exposed to a diagnostic concentration of CryIAc in a blue
      indicator diet. The bioassay provided rapid (24 h) diagnosis of the species
      composition of larvae tested and also monitored for the presence of resistance in
      H. virescens. An additional diagnostic concentration was established for
      monitoring resistance in H. zea. A probit model was used to compare the fecal
      production responses of insect strains over a range of CryIAc doses. Probability
      calculations, derived from our assay results, are also presented to aid in the
      interpretation of future results from field trials. Integration of the feeding
      disruption bioassay into integrated pest management programs is discussed.

PMID- 11233138
TI  - Efficacy of insecticides of different chemistries against Helicoverpa zea
      (Lepidoptera: Noctuidae) in transgenic Bacillus thuringiensis and conventional
      cotton.
AB  - Six insecticides of different chemistries were evaluated against the cotton
      bollworm, Helicoverpa zea (Boddie), in non-B.t. (Deltapine 'DP 5415', Deltapine
      'DP 5415RR') and transgenic Bacillus thuringiensis (Berliner) (B.t.) (Deltapine
      'NuCOTN 33B', Deltapine 'DP 458 B/RR') cotton. In 1998, treatments consisted of
      three rates each of a pyrethroid (lambda-cyhalothrin), spinosyn (spinosad),
      carbamate (thiodicarb), pyrrole (chlorfenapyr), oxadiazine (indoxacarb), and
      avermectin (emamectin benzoate) in a nonirrigated field. In 1999, treatments
      consisted of three rates each of lambda-cyhalothrin, spinosad, thiodicarb, and
      indoxacarb in an irrigated and a nonirrigated (dryland) field. The highest rate
      of each insecticide corresponded to normal grower-use rates. Spinosad and
      thiodicarb controlled H. zea in non-B.t. cotton, whereas other materials were
      less effective. Even though H. zea is becoming increasingly resistant to
      pyrethroid insecticides, lambda-cyhalothrin was highly effective in dryland B.
      thuringiensis cotton. Spinosad and thiodicarb were equally effective. Data
      indicated that reduced rates of lambda-cyhalothrin, spinosad, and thiodicarb
      could be used for control of H. zea in dryland B.t. cotton systems. However,
      reduced rates of these insecticides in a heavily irrigated B.t. cotton system did
      not provide adequate control.

PMID- 11233139
TI  - Potato leafhopper (Homoptera: Cicadellidae) injury disrupts basal transport of
      14C-labelled photoassimilates in alfalfa.
AB  - The potato leafhopper, Empoasca fabae (Harris), is a key pest of alfalfa,
      Medicago sativa L., in part because of the leafhopper's ability to disrupt upward
      translocation within phloem tissues. To determine if leafhopper injury also
      disrupts basal translocation necessary for regrowth and perenniality of alfalfa,
      we used radiolabeled 14CO2 to measure the basal transport of photoassimilates in
      injured and healthy plants. In one experiment, less 14C was transported to lower
      stem tissue of leafhopper-injured plants in comparison to the same tissue of
      healthy plants in early vegetative and early reproductive stages of alfalfa
      development. In a second experiment, less 14C was transported to lower stem,
      crown, and root tissues of injured plants in comparison to the same tissues of
      healthy, early reproductive plants. The disruption of basal transport caused by
      potato leafhopper may impact carbon storage and mobilization subsequent to
      defoliation, winter survival, and nitrogen fixation.

PMID- 11233140
TI  - Predicting western corn rootworm (Coleoptera: Chrysomelidae) larval injury to
      rotated corn with Pherocon AM traps in soybeans.
AB  - Crop rotation for portions of east central Illinois and northern Indiana no
      longer adequately protects corn (Zea mays L.) roots from western corn rootworm,
      Diabrotica virgifera virgifera LeConte. Seventeen growers in east central
      Illinois monitored western corn rootworm adults in soybean (Glycine max L.)
      fields with unbaited Pherocon AM traps during 1996 and 1997. In the following
      years (1997 and 1998), growers left untreated strips (no insecticide applied)
      when these fields were planted with corn. Damage to rotated corn by rootworms was
      more severe in untreated than in treated strips of rotated corn, ranging from
      minor root scarring to a full node of roots pruned. Densities of western corn
      rootworms in soybean fields from 1996 were significantly correlated with root
      injury to rotated corn the following season. Adult densities from 1997 were not
      significantly correlated with root injury in 1998, due to heavy precipitation
      throughout the spring of 1998 and extensive larval mortality. Twenty-eight
      additional growers volunteered in 1998 to monitor rootworm adults in soybean
      fields with Pherocon AM traps based on recommendations that resulted from our
      research efforts in 1996 and 1997. In 1999, these 28 fields were rotated to corn,
      and rootworm larval injury was measured in untreated strips. Based on 1996-1997
      and 1998-1999 data, a regression analysis revealed that 27% of the variation in
      root injury to rotated corn could be explained by adult density in soybeans the
      previous season. We propose a sampling plan for soybean fields and a threshold
      for predicting western corn rootworm larval injury to rotated corn.

PMID- 11233141
TI  - From cytoprotection to tumor suppression: the multifactorial role of
      peroxiredoxins.
AB  - In the past decade, a new family of highly conserved antioxidant enzymes,
      Peroxiredoxins (Prxs), have been discovered and defined. There are two major Prx
      subfamilies: one subfamily uses two conserved cysteines (2-Cys) and the other
      uses 1-Cys to scavenge reactive oxygen species (ROS). This review focuses on the
      four mammalian 2-Cys members (Prx I-IV) that utilize thioredoxin as the electron
      donor for antioxidation. The array of biological activities of these proteins
      suggests that they may be evolutionarily important for cell function. For
      example, Prxs are capable of protecting cells from ROS insult and regulating the
      signal transduction pathways that utilize c-Abl, caspases, nuclear factor-kappaB
      (NF-kappaB) and activator protein-1 (AP-1) to influence cell growth and
      apoptosis. Prxs are also essential for red blood cell (RBC) differentiation and
      are capable of inhibiting human immunodeficiency virus (HIV) infection and organ
      transplant rejection. Distribution patterns indicate that Prxs are highly
      expressed in the tissues and cells at risk for diseases related to ROS toxicity,
      such as Alzheimer's and Parkinson's diseases and atherosclerosis. This
      interesting correlation suggests that Prxs are protective against ROS toxicity,
      yet overwhelmed by oxidative stress in some cells. Prxs tend to form large
      aggregates at high concentrations, a feature that may interfere with their normal
      protective function or may even render them cytotoxic. Imbalance in the
      expression of subtypes can also potentially increase their susceptibility to
      oxidative stress. Understanding the function and biological role of Prxs may lead
      to important discoveries about the cellular dysfunction of ROS-related diseases
      ranging from atherosclerosis to cancer to neurodegenerative diseases.

PMID- 11233142
TI  - Redox regulation of the glucocorticoid receptor.
AB  - Redox regulation is currently considered as a mode of signal transduction for
      coordinated regulation of a variety of cellular processes. The transcriptional
      regulation of gene expression is also influenced by cellular redox state, most
      possibly through the oxido-reductive modification of transcription factors. The
      glucocorticoid receptor belongs to a nuclear receptor superfamily and acts as a
      ligand-dependent transcription factor. We demonstrate that the glucocorticoid
      receptor function is regulated via redox-dependent mechanisms at multiple levels.
      Moreover, it is suggested that redox regulation of the receptor function is one
      of dynamic cellular responses to environmental stimuli and plays an important
      role in orchestrated crosstalk between central and peripheral stress responses.

PMID- 11233143
TI  - Inflammation and the regulation of glutathione level in lung epithelial cells.
AB  - Inflammation is a highly complex biochemical protective response to cellular
      injury. If this process is continuously unchecked, it leads to chronic
      inflammation, a hallmark of various inflammatory lung diseases. Reactive oxygen
      intermediates generated by immune cells recruited to the sites of inflammation
      are a major cause of cell damage. Glutathione (GSH), is a vital intra- and
      extracellular protective antioxidant in the lungs. The rate-limiting enzyme in
      GSH synthesis is gamma-glutamylcysteine synthetase (gamma-GCS). Both GSH and
      gamma-GCS expression are modulated by oxidants, phenolic antioxidants,
      inflammatory, and anti-inflammatory agents in lung cells. GSH plays a key role in
      regulating oxidant-induced lung epithelial cell function and also in the control
      of pro-inflammatory processes. Alterations in the alveolar and lung GSH
      metabolism are widely recognized as a central feature of many inflammatory lung
      diseases. Oxidative processes have a fundamental role in lung inflammation
      through redox-sensitive transcription factors such as NF-kappaB and AP-1, which
      regulated the genes for pro-inflammatory mediators and protective antioxidant
      genes such as gamma-GCS. The critical balance between the induction of pro
      inflammatory mediators and antioxidant genes in response to oxidative stress at
      the site of inflammation is not known. Knowledge of the mechanisms of GSH
      regulation in lung inflammation could lead to the development of novel therapies
      based on the pharmacological manipulation of the production of this important
      antioxidant in lung inflammation and injury. This review describes the potential
      role of GSH for lung oxidant stress, inflammation and injury.

PMID- 11233144
TI  - Reactive nitrogen species in colon carcinogenesis.
AB  - The role of reactive nitrogen species (RNS) in colon carcinogenesis is
      multifactorial and affects diverse processes, such as proliferation, apoptosis,
      differentiation, tumorigenesis, and metastases. This review describes the stages
      in colon carcinogenesis where nitric oxide (NO) and inducible NO synthase (NOS2)
      may influence the progression of a normal mucosa to overt metastatic cancer.
      Overexpression of NOS2 and an increase in the generation of NO and other RNS may
      lead to apoptosis resistance, DNA damage, mutation, up-regulation of COX-2,
      increased proliferation, an increase in oxidative stress and an increase in tumor
      vascularity and metastatic potential. Therefore, future goals are to establish
      mechanistically based biomarkers to assess individuals at risk for colon cancer
      and to implement chemopreventive and dietary strategies that reduce colon cancer
      risk. An understanding of NO signaling pathways in colon epithelial cells should
      provide the basis for novel biomarker development. Colon cancer prevention may be
      achieved effectively by chemically interfering with key components of the NO
      signaling pathways, changing dietary habits to reduce fat and increase
      antioxidant-containing vegetables, and dietary supplementation to increase DNA
      repair.

PMID- 11233145
TI  - Ginkgo biloba leaf extract: review of biological actions and clinical
      applications.
AB  - The number of studies on Ginkgo biloba leaves is rapidly increasing. A variety of
      effects of Ginkgo biloba leaf extract (GBLE) have been identified. GBLE contains
      many different flavone glycosides and terpenoides. GBLE has an antioxidant action
      as a free radical scavenger, a relaxing effect on vascular walls, an antagonistic
      action on platelet-activating factor, an improving effect on blood flow or
      microcirculation, and a stimulating effect on neurotransmitters. Besides a direct
      scavenging action on active oxygen species, GBLE exerts an anti-inflammatory
      effect on inflammatory cells by suppressing the production of active oxygen and
      nitrogen species. GBLE inhibited the increase in the products of the oxidative
      decomposition low-density lipoprotein (LDL), reduced the cell death in various
      types of neuropathy, and prevented the oxidative damage to mitochondria,
      suggesting that GBLE exhibits beneficial effects on neuron degenerative diseases
      by preventing chronic oxidative damage. The study using a model of ischemia
      reperfusion injury has also demonstrated the protective effect of GBLE on cardiac
      muscle and its antioxidative action in vivo. Favorable results have been obtained
      in double-blind, placebo-controlled, comparative trials of patients with memory
      disorders, obstructive arteriosclerosis, and dementia. We review the recent
      studies on GBLE with respect to its various pharmacological actions, such as a
      scavenging activity on free radicals and an inhibitory action on lipid
      peroxidation. GBLE shows a very strong scavenging action on free radicals, and is
      thus considered to be useful for the treatment of diseases related to the
      production of free radicals, such as ischemic heart disease, cerebral infarction,
      chronic inflammation, and aging.

PMID- 11233146
TI  - Pharmacologic properties of phenyl N-tert-butylnitrone.
AB  - Phenyl N-tert-butylnitrone (PBN) is the parent of a family of nitrones used as
      spin-trapping agents to trap free radicals. PBN's pharmacological effects in
      animal models are extensive, ranging from protection against death after
      endotoxin shock, protection from ischemia-reperfusion injury, to increasing the
      life span of mice. Recent additions to the list include protection from bacterial
      meningitis, thalidomide-induced teratogenicity, drug-induced diabetogenesis, and
      choline-deficient hepatocarcinogenesis. Because PBN reacts with oxygen radicals
      to produce less reactive species, it has been suggested that this is the basis of
      its pharmacological effects. However, there has been no hard evidence for this
      notation. Nevertheless, many investigators have used the presence of PBN's
      pharmacologic effect as evidence for free radical involvement in their models.
      Mechanistic studies on the PBN's antisepsis action revealed that PBN inhibits
      expression of various pro-inflammatory genes, suggesting that the protective
      action involves more than a straightforward free radical-scavenging mechanism.
      Previous and recent developments in the investigations on the pharmacologic
      properties of PBN are described in this review.

PMID- 11233147
TI  - Elevation of intracellular calcium ions is essential for the H2O2-induced
      activation of SAPK/JNK but not for that of p38 and ERK in Chinese hamster V79
      cells.
AB  - The mitogen-activated protein kinases (MAPK), including stress-activated protein
      kinase/c-Jun N-terminal kinase (SAPK/JNK), p38, and extracellular signal-related
      kinase (ERK), are believed to be important biomolecules in cell proliferation,
      survival, and apoptosis induced by extracellular stimuli. In Chinese hamster V79
      cells exposed to hydrogen peroxide (H2O2), we recently demonstrated that SAPK/JNK
      was activated by tyrosine kinase and intracellular Ca2+ ([Ca2+]i). In this study,
      we report that [Ca2+]i release from intracellular stores is important in the
      activation of SAPK/JNK but not p38 and ERK. H2O2-induced elevation of [Ca2+]i was
      observed in Ca2+-free medium. Pretreatment with thapsigargin, a Ca2+-ATPase
      inhibition of endoplasmic reticulum (ER), did not influence H2O2-induced
      elevation of [Ca2+]i in the absence of external Ca2+. An intracellular Ca2+
      chelator (BAPTA-AM) inhibited H2O2-induced phosphorylation of SAPK/JNK, but an
      extracellular Ca2+ chelator (EDTA) or a Ca2+ entry blocker (NiCl2) did not.
      Activation of p38 and ERK in V79 cells exposed to H2O2 was observed in the
      presence of these inhibitors. These results suggest that [Ca2+]i release from
      intracellular stores such as mitochondria or nuclei but not ER, occurred after
      H2O2 treatment and Ca2+-dependent tyrosine kinase-induced activation of SAPK/JNK,
      although [Ca2+]i was unnecessary for the H2O2-induced activation of p38 and ERK.

PMID- 11233148
TI  - Intracellular effects of nitric oxide on force production and Ca2+ sensitivity of
      cardiac myofilaments.
AB  - The gaseous free radical nitric oxide (NO*) has been implicated in a wide range
      of physiological functions and also has a role in the pathogenesis of cellular
      injury. It has been suggested that NO* and its congeners may exert effects on
      actin-myosin crossbridge cycling by modulating critical thiols on the myosin
      head. To understand the mode and site of actin of NO* in myofibrils, the effects
      of the NO* donor 3-(2-hydroxy-1-methyl-2-nitrosohydrazine)-N-methyl-1-propanamine
      (NOC-7) have been studied in Triton X-100-treated rabbit cardiac fibers, in which
      isometric force was measured at controlled degrees of activation. Experiments
      were undertaken after previous exposure of the preparations to NOC-7 (for 30
      min). We found that NO* induced several alterations of myofibrillar function,
      i.e., decrease in Ca2+ sensitivity and Hill coefficient and potentiation of rigor
      contracture. We attributed the effect on rigor contracture to strong inhibition
      of myofibrillar creatine kinase (CK) activity, because it could be prevented by
      exogeneously added CK; such CK inactivation afforded by NO* may result in the
      myofibrillar ATP-to-ADP ratio. In further experiments, concentration of NO*
      released from NOC-7 was determined by the electron spin resonance spin-trapping
      technique; N-(dithiocarboxy)sarcosine-Fe2+ complex was used as the spin-trap. NO*
      at cumulative concentration of 0.69 microM was effective in producing both
      enhancement of rigor contracture and decrease of myofibrillar-bound CK activity;
      however, Ca2+-sensitivity (pCa50) was significantly decreased at >5.6 microM of
      NO*, suggesting a result from different mechanisms. Thus, the observed decrease
      in Ca2+ sensitivity seems to be associated with direct modification of the
      regulatory proteins by a relatively higher concentration of NO*, and possibly not
      via inhibition of myofibrillar CK activity. The data reported here indicate that
      CK may be a pathophysiologically main target for increased NO* formation at low
      molecular range in the disease state in cardiac muscle.

PMID- 11233149
TI  - Metabolic effects of gamma-linolenic acid-alpha-lipoic acid conjugate in
      streptozotocin diabetic rats.
AB  - Data suggesting the involvement of increased oxidative stress in the
      pathophysiology of diabetes has raised interest in the potential therapeutic
      benefit of antioxidants. Although beneficial metabolic effects of antioxidant
      supplementation have been suggested, an antioxidant mode of action, particularly
      in skeletal muscle, has not been documented. In the present study, we evaluate
      the metabolic effects of a gamma-linolenic acid-alpha-lipoic acid conjugate (GLA
      LA) in streptozotocin-induced diabetic rats, and assess its potential mode of
      action by comparing its effects with equimolar administration of LA and GLA
      alone. Ten days of oral supplementation of 20 mg/kg body weight GLA-LA, but not
      LA or GLA alone, caused a mild reduction in fasting blood glucose concentration
      as compared with vehicle-treated diabetic rats (375 +/- 11 vs. 416 +/- 16 mg/dl,
      p = 0.03), with no change in fasting plasma insulin levels. A peripheral insulin
      sensitizing effect could be observed with GLA-LA, LA, and GLA treatments, as
      demonstrated by a significant (p < 0.04) 23%, 13%, and 10% reduction,
      respectively, in the area under the glucose curve following an intravenous
      insulin tolerance test. This effect was associated with a 67% and 50% increase in
      GLUT4 protein content in the membranes of gastrocnemius muscle of GLA-LA and LA
      treated animals, respectively; however, no change was observed with GLA treatment
      alone. Interestingly, both GLA-LA and LA treatments corrected a diabetes-related
      decrease in the gastrocnemius muscle low-molecular-weight reduced thiols content.
      These data demonstrate insulin-sensitizing properties of the GLA-LA conjugate by
      distinct mechanisms attributable to each of its components, which are associated
      with antioxidant effects.

PMID- 11233150
TI  - Free radical scavenging activity in the nonenzymatic fraction of human saliva: a
      simple DPPH assay showing the effect of physical exercise.
AB  - Free-radicals and other reactive oxygen species (ROS) have been implicated as
      being major damaging species in pathology and they have been widely investigated.
      Using 1,1'-diphenyl-2-picrylhydrazyl (DPPH), we estimated total free radical
      scavenging activity in the low-molecular-weight nonenzymatic fraction (LMNEF) of
      human whole saliva. The activity of the whole saliva and serum were measured in
      terms of the rate of decrease in the absorbance at 517 nm in a 40% ethanol DPPH
      solution (pH 7.4) at room temperature. The DPPH activity of saliva and serum
      showed a significant linear relationship. The mean DPPH activities of saliva from
      257 subjects aged 4-72 was found to be 0.389+/-.190 micromol/ml and bore no
      relation to age or sex. The activity in saliva of 86 subjects aged 4-11 was
      significantly different before and after exhaustive aerobic dance exercise for 1
      hr. Physical exercise markedly decreased free radical scavenging activity in
      whole saliva of children. On the basis of the above results, we concluded that
      DPPH is useful for evaluating the total antioxidant capacity of LMNEF of human
      saliva.

PMID- 11233151
TI  - Action of pyrroloquinolinequinol as an antioxidant against lipid peroxidation in
      solution.
AB  - The activities of pyrroloquinoline quinone (PQQ), a coenzyme of methanol
      dehydrogenase and amine oxidase, and its reduced form pyrroloquinoline quinol
      (PQQH2) as an antioxidant have been measured in solution. PQQH2 was stable in the
      absence of oxygen but rapidly auto-oxidized to PQQ in the presence of oxygen in
      water. PQQH2 was stable in an aprotic solvent such as acetonitrile, even in air.
      PQQ did not exert appreciable antioxidant activity, whereas PQQH2 exerted higher
      reactivity than alpha-tocopherol toward galvinoxyl radical and peroxyl radical.
      PQQH2 acted as a potent antioxidant against the oxidation of methyl linoleate in
      acetonitrile induced by azo compound and produced a clear induction period, from
      which the apparent stoichiometric number was obtained as 1.1. PQQH2 reduced the
      alpha-tocopheroxyl radical and spared alpha-tocopherol in the oxidation of methyl
      linoleate. These results suggest that PQQH2 may act as a potent antioxidant,
      particularly in combination with alpha-tocopherol.

PMID- 11233152
TI  - A novel water-soluble vitamin E derivative protects against experimental colitis
      in rats.
AB  - This study was designed to investigate the effects of water-soluble vitamin E
      derivative, 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol
      (TMG), on experimental colitis in rats. Colitis was induced in male Wistar rats
      weighing 200 grams using an enema of trinitrobenzene sulfonic acid (TNBS)
      dissolved in 50% ethanol; 1 ml of TMG dissolved in physiological saline (0.2
      mg/ml, 2 mg/ml, 20 mg/ml) was injected intraperitoneally every day for 1 week
      after the enema. The damage score, wet weight of the colon, and increase in body
      weight were estimated 1 week after the enema of TNBS. Thiobarbituric acid
      reactive substances (TBA-RS), an index of lipid peroxidation, and the level of
      alpha-tocopherol or TMG in the colonic mucosa were measured 1 week after the
      induction of colitis. As a result, increase in body weight was inhibited by the
      induction of colitis, although the inhibition was reduced in the group treated
      with TMG. The damage score, wet weight and TBA-RS were increased significantly in
      the colitis group; however, they were inhibited by the administration of TMG. The
      alpha-tocopherol level in the colonic mucosa was reduced by the induction of
      colitis, wheres TMG could not be detected in the colonic mucosa of rats treated
      with TMG. These results suggest that TMG is effective for the treatment of
      colitis in rats induced by TNBS.

PMID- 11233153
TI  - Amelioration of the cytotoxic effects of chemotherapeutic agents by grape seed
      proanthocyanidin extract.
AB  - Anticancer chemotherapeutic agents are effective in inhibiting growth of cancer
      cells in vitro and in vivo, however, toxicity to normal cells is a major problem.
      In this study, we assessed the effect of a novel IH636 grape seed
      proanthocyanidin extract (GSPE) to ameliorate chemotherapy-induced toxic effects
      in cultured Chang epithelial cells, established from nonmalignant human tissue.
      These cells were treated in vitro with idarubicin (Ida) (30 nM) or 4
      hydroxyperoxycyclophosphamide (4HC) (1 microg/ml) with or without GSPE (25
      microg/ml). The cells were grown in vitro and the growth rate of the cells was
      determined using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide; thiazolyl blue] assay. Our results showed that GSPE decreased the growth
      inhibitory and cytotoxic effects of Ida as well as 4HC on Chang epithelial cells
      in vitro. Because these chemotherapeutic agents are known to induce apoptosis in
      the target cells, we analyzed the Chang epithelial cells for apoptotic cell
      population by flow cytometry. There was a significant decrease in the number of
      cells undergoing apoptosis following treatment with GSPE. We also found increased
      expression of the anti-apoptotic protein Bcl-2 in GSPE-treated cells using
      western blot techniques. Thus, these results indicate that GSPE can be a
      potential candidate to ameliorate the toxic effects associated with
      chemotherapeutic agents and one of the mechanisms of action of GSPE includes
      upregulation of Bcl-2 expression.

PMID- 11233154
TI  - AOP2 (antioxidant protein 2): structure and function of a unique thiol-specific
      antioxidant.
AB  - The accumulation of reactive oxygen species (ROS) in response to extracellular
      signals or intracellular biochemical processes can be regulated by the coordinate
      action of many antioxidant proteins. Because moderate levels of ROS can act as
      intracellular messengers in many of these processes, this modulation is critical
      for the transduction of specific signals. The thiol-specific antioxidant (TSA)
      family is a highly conserved group of enzymes that can reduce hydroperoxides in
      the presence of a thiol-containing electron donor. AOP2 (antioxidant protein 2)
      is a newly described member that shows significant evolutionary conservation
      between many different organisms. The protein contains three motifs that are
      highly conserved within the TSA family, including a cysteine residue that is the
      active site of oxidation for this class of proteins. Although AOP2 possesses TSA
      activity, it has several unique characteristics, including the absence of a
      second cysteine residue that is conserved in all other TSA proteins, the presence
      of a unique carboxy-terminal domain, and a demonstrated phospholipase activity.
      Furthermore, AOP2 shows conservation of several amino acids important in dimer
      formation and active site configuration that are not found in the other family
      members. Together, these data strongly suggest that AOP2 is a novel thiol
      dependent antioxidant that functions to scavenge particular hydroperoxides in the
      cell and mediate specific signals. There is also evidence supporting a role for
      AOP2 in certain disease processes including atherosclerosis. Further evaluation
      of this protein and its substrate specificity will likely shed light on its
      precise role in cellular oxidant defense, signal transduction and pathogenesis.

PMID- 11233155
TI  - Macrophage foam cell formation during early atherogenesis is determined by the
      balance between pro-oxidants and anti-oxidants in arterial cells and blood
      lipoproteins.
AB  - Atherosclerosis is a multifactorial disease, where more than one mechanism, along
      more than one step, contributes to macrophage cholesterol accumulation and foam
      cell formation, the hallmark of early atherogenesis. Arterial macrophages take up
      oxidized low-density lipoproteins (Ox-LDL), leading to cellular accumulation of
      cholesterol and oxysterols. Atherogenic modifications of LDL include, in addition
      to oxidation, retention and aggregation. Intervention to inhibit LDL oxidation
      can affect the above additional LDL modifications. Indeed, we have demonstrated
      in the atherosclerotic apolipoprotein E-deficient mice that consumption of
      vitamin E or of flavonoids from red wine or licorice decreased LDL oxidation, LDL
      retention, and LDL aggregation and attenuated macrophage foam cell formation and
      atherosclerosis. The balance between pro-oxidants and anti-oxidants in the LDL
      particle (such as cholesteryl ester vs. vitamin E), as well as in arterial wall
      macrophages (such as NADPH oxidase vs. glutathione), determines the extent of LDL
      oxidation. Antioxidants can protect LDL from oxidation not only by their binding
      to the lipoprotein, but also following their accumulation in cells of the
      arterial wall. Whereas antioxidants can prevent the formation of Ox-LDL, human
      serum paraoxonase (PON 1), an HDL-associated esterase that hydrolyzes
      organophosphates, can eliminate oxidized LDL (by hydrolysis of its lipid
      peroxides), which is formed when antioxidant protection is not sufficient. Ox
      LDL, in turn, can inactivate paraoxonase activity. Thus, the combination of
      antioxidants together with active paraoxonase decreases the formation of Ox-LDL
      and preserves PON1's ability to hydrolyze this atherogenic lipoprotein and hence,
      to attenuate atherosclerosis.

PMID- 11233156
TI  - New perspectives on anaerobic methane oxidation.
AB  - Anaerobic methane oxidation is a globally important but poorly understood
      process. Four lines of evidence have recently improved our understanding of this
      process. First, studies of recent marine sediments indicate that a consortium of
      methanogens and sulphate-reducing bacteria are responsible for anaerobic methane
      oxidation; a mechanism of 'reverse methanogenesis' was proposed, based on the
      principle of interspecies hydrogen transfer. Second, studies of known methanogens
      under low hydrogen and high methane conditions were unable to induce methane
      oxidation, indicating that 'reverse methanogenesis' is not a widespread process
      in methanogens. Third, lipid biomarker studies detected isotopically depleted
      archaeal and bacterial biomarkers from marine methane vents, and indicate that
      Archaea are the primary consumers of methane. Finally, phylogenetic studies
      indicate that only specific groups of Archaea and SRB are involved in methane
      oxidation. This review integrates results from these recent studies to constrain
      the responsible mechanisms.

PMID- 11233157
TI  - Differential inhibition in vivo of ammonia monooxygenase, soluble methane
      monooxygenase and membrane-associated methane monoxygenase by phenylacetylene.
AB  - Phenylacetylene was investigated as a differential inhibitor of ammonia
      monooxygenase (AMO), soluble methane monooxygenase (sMMO) and membrane-associated
      or particulate methane monooxygenase (pMMO) in vivo. At phenylacetylene
      concentrations > 1 microM, whole-cell AMO activity in Nitrosomonas europaea was
      completely inhibited. Phenylacetylene concentrations above 100 microM inhibited
      more than 90% of sMMO activity in Methylococcus capsulatus Bath and Methylosinus
      trichosporium OB3b. In contrast, activity of pMMO in M. trichosporium OB3b, M.
      capsulatus Bath, Methylomicrobium album BG8, Methylobacter marinus A45 and
      Methylomonas strain MN was still measurable at phenylacetylene concentrations up
      to 1,000 microM. AMO of Nitrosococcus oceanus has more sequence similarity to
      pMMO than to AMO of N. europaea. Correspondingly, AMO in N. oceanus was also
      measurable in the presence of 1,000 microM phenylacetylene. Measurement of oxygen
      uptake indicated that phenylacetylene acted as a specific and mechanistic-based
      inhibitor of whole-cell sMMO activity; inactivation of sMMO was irreversible,
      time dependent, first order and required catalytic turnover. Corresponding
      measurement of oxygen uptake in whole cells of methanotrophs expressing pMMO
      showed that pMMO activity was inhibited by phenylacetylene, but only if methane
      was already being oxidized, and then only at much higher concentrations of
      phenylacetylene and at lower rates compared with sMMO. As phenylacetylene has a
      high solubility and low volatility, it may prove to be useful for monitoring
      methanotrophic and nitrifying activity as well as identifying the form of MMO
      predominantly expressed in situ.

PMID- 11233158
TI  - Crenarchaeota colonize terrestrial plant roots.
AB  - Microorganisms that colonize plant roots are recruited from, and in turn
      contribute substantially to, the vast and virtually uncharacterized phylogenetic
      diversity of soil microbiota. The diverse, but poorly understood, microorganisms
      that colonize plant roots mediate mineral transformations and nutrient cycles
      that are central to biosphere functioning. Here, we report the results of
      epifluorescence microscopy and culture-independent recovery of small subunit
      (SSU) ribosomal RNA (rRNA) gene sequences showing that members of a previously
      reported clade of soil Crenarchaeota colonize both young and senescent plant
      roots at an unexpectedly high frequency, and are particularly abundant on the
      latter. Our results indicate that non-thermophilic members of the Archaea inhabit
      an important terrestrial niche on earth and direct attention to the need for
      studies that will determine their possible roles in mediating root biology.

PMID- 11233159
TI  - Monitoring of activity dynamics of an anaerobic digester bacterial community
      using 16S rRNA polymerase chain reaction--single-strand conformation polymorphism
      analysis.
AB  - The influence of parameter changes on the bacterial community of a laboratory
      scale anaerobic digester fed with glucose was investigated using a culture
      independent approach based on single-strand conformation polymorphism (SSCP)
      analysis of total 16S rDNA and 16S rRNA amplification products. With the digester
      operating at steady state, the 16S rDNA SSCP patterns of the bacterial community
      showed eight peaks, whereas the 16S rRNA patterns showed six peaks with a very
      prominent one corresponding to a Spirochaetes-related bacterium. An acidic shock
      at pH 6 caused an increase in the 16S rRNA level of two Clostridium-related
      bacteria. After a 1 week starvation period, the major bacteria present reverted
      to a basal 16S rRNA level proportional to their 16S rDNA level. Starvation
      revealed the presence of a previously undetected peak whose corresponding
      sequence was deeply branched into the low G+C Gram-positive bacteria phylum.
      Twenty-four hours after a spiked addition to the starved digester community of
      starch, glucose, lactate or sulphate, an upsurge in several new 16S rRNA-derived
      peaks was observed. Thus, the perturbation approach combined with 16S rRNA
      analysis revealed bacteria that had not been detected through 16S rDNA analysis.

PMID- 11233160
TI  - Construction and analysis of bacterial artificial chromosome libraries from a
      marine microbial assemblage.
AB  - Cultivation-independent surveys of ribosomal RNA genes have revealed the
      existence of novel microbial lineages, many with no known cultivated
      representatives. Ribosomal RNA-based analyses, however, often do not provide
      significant information beyond phylogenetic affiliation. Analysis of large genome
      fragments recovered directly from microbial communities represents one promising
      approach for characterizing uncultivated microbial species better. To assess
      further the utility of this approach, we constructed large-insert bacterial
      artificial chromosome (BAC) libraries from the genomic DNA of planktonic marine
      microbial assemblages. The BAC libraries we prepared had average insert sizes of
      80 kb, with maximal insert sizes > 150 kb. A rapid screening method assessing the
      phylogenetic diversity and representation in the library was developed and
      applied. In general, representation in the libraries agreed well with previous
      culture-independent surveys based on polymerase chain reaction (PCR)amplified
      rRNA fragments. A significant fraction of the genome fragments in the BAC
      libraries originated from as yet uncultivated microbial species, thought to be
      abundant and widely distributed in the marine environment. One entire BAC insert,
      derived from an uncultivated, surface-dwelling euryarchaeote, was sequenced
      completely. The planktonic euryarchaeal genome fragment contained some typical
      archaeal genes, as well as unique open reading frames (ORFs) suggesting novel
      function. In total, our results verify the utility of BAC libraries for providing
      access to the genomes of as yet uncultivated microbial species. Further analysis
      of these BAC libraries has the potential to provide significant insight into the
      genomic potential and ecological roles of many indigenous microbial species,
      cultivated or not.

PMID- 11233161
TI  - A novel and sensitive method for the quantification of N-3-oxoacyl homoserine
      lactones using gas chromatography-mass spectrometry: application to a model
      bacterial biofilm.
AB  - A method is reported for the quantification of 3-oxoacyl homoserine lactones (3
      oxo AHLs), a major class of quorum-sensing signals found in Gram-negative
      bacteria. It is based on the conversion of 3-oxo AHLs to their
      pentafluorobenzyloxime derivatives followed by gas chromatography-mass
      spectrometry (electron capture-negative ion). The method used [13C16]-N-3-oxo
      dodecanoyl homoserine lactone ([13C16]-OdDHL) as the internal standard, and its
      validity was tested by spiking the supernatant and cell fractions with three
      levels of 3-oxo AHLs, i.e. 1, 10 and 100 ng per sample. These showed the method
      to be both sensitive (S/N ratio >10:1 for 1 ng) and accurate. The assay was
      applied to the biofilm and effluent of a green fluorescent protein (GFP)
      expressing strain of Pseudomonas aeruginosa (6294) culture grown in flow cells.
      Biofilm volume was determined for three replicate flow cells by confocal scanning
      laser microscopy. OdDHL was detected in the biofilm at 632 +/- 381 microM and the
      effluent at 14 +/- 3 nM. The biofilm concentration is the highest level so far
      reported for an AHL in a wild-type bacterial system. The next most abundant 3-oxo
      AHL in the biofilm and effluent was N-3-oxo-tetradecanoyl homoserine lactone
      (OtDHL) at 40 +/- 15 microM and 1.5 +/- 0.7 nM respectively. OtDHL is unreported
      for P. aeruginosa and has an activity equivalent to OdDHL in a lasR bioassay. Two
      other 3-oxo AHLs were detected at lower concentrations: N3-oxo-decanoyl
      homoserine lactone (ODHL) in the biofilm (3 +/- 2 microM) and effluent (1 +/- 0.1
      nM); and N-3-oxo-octanoyl homoserine lactone (OOHL) in the effluent (0.1 +/- 0.1
      nM).

PMID- 11233163
TI  - A gene containment strategy based on a restriction-modification system.
AB  - Engineering barriers to the spread of specific genes are of great interest both
      to increase the predictability of recombinant microorganisms used for
      environmental applications and to study the role of gene transfer in the
      adaptation of microbial communities to changing environments. We report here a
      new gene containment circuit based on a toxin-antidote pair that targets the cell
      DNA, i.e. the type II EcoRI restriction-modification system. The set-up involved
      linkage of the ecoRIR lethal gene encoding the EcoRI endonuclease (toxin) to the
      contained character in a plasmid and chromosomal insertion of the ecoRIM gene
      encoding the cognate EcoRI methylase (antidote) that protects the target DNA from
      restriction. Transfer of the contained character to a recipient cell lacking the
      antidote caused EcoRI-mediated chromosomal breaks, leading to cell death, thereby
      preventing gene spread. Using transformation and conjugation as mechanisms of DNA
      transfer and different environmentally relevant bacteria as recipients, we have
      shown that the potentially universal EcoRI-based containment system decreases
      gene transfer frequencies by more than four orders of magnitude. Analyses of the
      survivors escaping killing revealed a number of possible inactivation mechanisms.

PMID- 11233162
TI  - Characterization of depth-related population variation in microbial communities
      of a coastal marine sediment using 16S rDNA-based approaches and quinone
      profiling.
AB  - Depth-related changes in whole-community structure were evaluated in a coastal
      marine sediment using a molecular fingerprinting method, terminal restriction
      fragment length polymorphism (T-RFLP) analysis, and a chemotaxonomic technique
      (quinone profiling). Dendrograms derived from both T-RFLP analysis and quinone
      profiling indicated a significant variation in microbial community structure
      between the 0-2 cm layer and deeper layers. This corresponded to the dramatic
      change in the redox potential, acid-volatile sulphide-sulphur and bacterial
      numbers observed at 0-2 cm and 2-4 cm depths. A significant change in the number
      of terminal restriction fragments (T-RFs) was also detected at this transition
      depth. However, the change in major T-RFs with depth was not seen in
      electropherograms. The population changes were primarily variations in minor
      ribotypes. Most quinone homologues were detected at all depths, although the
      quinone composition changed with depth. Therefore, quinone profiling also
      suggested that the depth-related variation was primarily attributable to minor
      bacterial groups rather than change in the major population structure. 16S rDNA
      clone library analysis revealed that clones belonging to the genera Vibrio and
      Serratia predominated as major bacterial groups at all depths. Our data suggested
      that the sediment community might result from sedimentation effects of sinking
      particles. Overall, our results demonstrated that the combined methods of T-RFLP
      analysis and quinone profiling were effective for assessing depth-related
      microbial populations.

PMID- 11233164
TI  - Artificial selection of microbial ecosystems for 3-chloroaniline biodegradation.
AB  - We present a method for selecting entire microbial ecosystems for bioremediation
      and other practical purposes. A population of ecosystems is established in the
      laboratory, each ecosystem is measured for a desired property (in our case,
      degradation of the environmental pollutant 3-chloroaniline), and the best
      ecosystems are used as 'parents' to inoculate a new generation of 'offspring'
      ecosystems. Over many generations of variation and selection, the ecosystems
      become increasingly well adapted to produce the desired property. The procedure
      is similar to standard artificial selection experiments except that whole
      ecosystems, rather than single individuals, are the units of selection. The
      procedure can also be understood in terms of complex system theory as a way of
      searching a vast combinatorial space (many thousands of microbial species and
      many thousands of genes within species) for combinations that are especially good
      at producing the desired property. Ecosystem-level selection can be performed
      without any specific knowledge of the species that comprise the ecosystems and
      can select ensembles of species that would be difficult to discover with more
      reductionistic methods. Once a 'designer ecosystem' has been created by ecosystem
      level selection, reductionistic methods can be used to identify the component
      species and to discover how they interact to produce the desired effect.

PMID- 11233166
TI  - Web alert. Bioluminescence and microorganisms.

PMID- 11233165
TI  - Detection of genes for alkane and naphthalene catabolism in Rhodococcus sp.
      strain 1BN.
AB  - Rhodococcus sp. 1BN was isolated from a contaminated site and showed various
      biodegradative capabilities. Besides naphthalene, strain 1BN degraded medium-
      (C6) and long-chain alkanes (C16-C28), benzene and toluene, alone or when the
      hydrocarbons were mixed in equal proportions. The nucleotide sequence of an alk
      polymerase chain reaction (PCR) fragment revealed a 59% nucleotide homology to
      the Pseudomonas oleovorans alkB gene. The nar fragments were highly homologous to
      genes coding for large and small subunits of cis-naphthalene 1,2-dioxygenase
      (narAa and narAb) and to cis-naphthalene dihydrodiol dehydrogenase (narB) from
      other rhodococci. The oxidation of indene to cis-(1S,2R)-1,2-dihydroxyindan by
      toluene-induced cells allows to hypothesize that strain 1BN also carries a
      toluene dioxygenase-like system.

PMID- 11233167
TI  - Identification, using molecular dynamics, of an effector domain of the ras
      binding domain of the raf-p74 protein that is uniquely involved in oncogenic ras
      p21 signaling.
AB  - By comparing the average structures, computed using molecular dynamics, of the
      ras-binding domain of raf (RBD) bound to activated wild-type ras-p21 and its
      homologous inhibitory protein, rap-1A, we formerly identified three domains of
      the RBD that changed conformation between the two complexes, residues 62-76, 97
      110, and 111-121. We found that one synthetic peptide, corresponding to RBD
      residues 97-110, selectively inhibited oncogenic ras-p21-induced oocyte
      maturation. In this study, we performed molecular dynamics on the Val 12-ras-p21
      RBD complex and compared its average structure with that for the wild-type
      protein. We find that there is a large displacement of a loop involving these
      residues when the structures of the two complexes are compared. This result
      corroborates our former finding that the RBD 97-110 peptide inhibits only signal
      transduction by oncogenic ras-p21 and suggests that oncogenic p21 uses this loop
      to interact with raf in a unique manner.

PMID- 11233168
TI  - Effects of zinc on creatine kinase: activity changes, conformational changes, and
      aggregation.
AB  - The effects of zinc on creatine kinase (CK) are very distinctive compared with
      other bivalent metal ions. Zinc up to 0.1 mM induced increases in CK activity,
      accompanied by significant hydrophobic surface exposure and increase in alpha
      helix content of CK. Zinc over 0.1 mM denatured and inactived CK. In the presence
      of 0.1 mM zinc, the CK activity was very close to that of the native CK, but its
      conformation changed greatly. The kinetic courses of CK inactivation and
      conformational change in the presence of 1 mM zinc were measured to determine
      apparent rate constants of inactivation and conformational change. Zinc over 0.05
      mM induced CK aggregation at 37 degrees C, and the aggregation was dependent on
      zinc concentration, CK concentration, and temperature. The inactivation and
      aggregation can be reversed by EDTA. An explanation for CK aggregation induced by
      zinc is proposed, as well as a mechanism for CK abnormality in Alzheimer's
      disease.

PMID- 11233169
TI  - Enzyme-induced covalent modification of methionyl-tRNA synthetase from Bacillus
      stearothermophilus by methionyl-adenylate: identification of the labeled amino
      acid residues by matrix-assisted laser desorption-ionization mass spectrometry.
AB  - Methionyl-tRNA synthetase (MetRS) from Bacillus stearothermophilus was shown to
      undergo covalent methionylation by a donor methionyl-adenylate, the mixed
      carboxylic-phosphoric acid anhydride synthesized by the enzyme itself. Covalent
      reaction of methionyl-adenylate with the synthetase or other proteins proceeds
      through the formation of an isopeptide bond between the carboxylate of the amino
      acid and the epsilon-NH2 group of lysyl residues. The stoichiometries of
      labeling, as followed by TCA precipitation, were 2.2 +/- 0.1 and 4.3 +/- 0.1 mol
      of [14C]Met incorporated by 1 mol of the monomeric MS534 and the native dimeric
      species of B. stearo methionyl-tRNA synthetase, respectively. Matrix-assisted
      laser desorption-ionization mass spectrometry designated lysines-261, -295, -301
      and -528 (or -534) of truncated methionyl-tRNA synthetase as the target residues
      for covalent binding of methionine. By analogy with the 3D structure of the
      monomeric M547 species of E. coli methionyl-tRNA synthetase, lysines-261, -295,
      and -301 would be located in the catalytic crevice of the thermostable enzyme
      where methionine activation and transfer take place. It is proposed that, once
      activated by ATP, most of the methionine molecules react with the closest
      reactive lysyl residues.

PMID- 11233170
TI  - GroEL and protein disulfide isomerase each binds with folding intermediates of D
      glyceraldehyde-3-phosphate dehydrogenase released from complexes formed with the
      other.
AB  - Simultaneous presence of two chaperones, GroEL and protein disulfide isomerase
      (PDI), assists the reactivation of denatured D-glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) in an additive way. Delayed addition of chaperones to the
      refolding solution after dilution of denatured GAPDH indicates an interaction
      with intermediates formed mainly in the first 5 min for PDI and formed within a
      longer time period for GroEL-ATP. The above indicate that the two chaperones
      interact with different folding intermediates of GAPDH. After delayed addition of
      one chaperone to the refolding mixture containing the other at 4 degrees C, GroEL
      binds with all GAPDH intermediates dissociated from PDI, and PDI interacts with
      the intermediates released from GroEL during the first 10-20 min. It is suggested
      that the GAPDH folding intermediates released from the chaperone-bound complex
      are still partially folded so as to be rebound by the other chaperone. The above
      results clearly support the network model of GroEL and PDI.

PMID- 11233172
TI  - Wavelength-dependent spectral changes accompany CN-hemin binding to human
      apohemoglobin.
AB  - The interaction of apohemoglobin with two heme derivatives, CN-protohemin and CN
      deutero-hemin, was monitored at multiple Soret wavelengths (417-423 and 406-412
      nm, respectively) in 0.05 M potassium phosphate buffer, pH 7.0, at 10 degrees C
      and revealed, as previously reported, a multiphasic kinetic reaction. Wavelength
      dependent reactions were observed for both CN-protohemin and CN-deuterohemin
      derivatives with the alpha chain (bathochromic entity) displaying faster (4- to 7
      fold) rates throughout the courses of both heme-binding reactions. The basis of
      this spectrally heterogeneous kinetic phenomenon could be deduced from molecular
      modeling studies of alpha- and beta-chain structures. Key differences in the
      number of stabilizing contacts of the two chains with the peripheral alpha
      propionyl 45(CE3); 58(E7); 61(E10) as well as the beta vinyl 38(C4); 71(E15);
      106(G8) groups were found. Furthermore, RMS plots comparing apo- and heme
      containing subunits reveal substantial structural disparities in the C-CD-F-FG
      helical regions of the alphabeta dimer interface.

PMID- 11233171
TI  - Characterization of nicking of the nontoxic-nonhemagglutinin components of
      Clostridium botulinum types C and D progenitor toxin.
AB  - Clostridium botulinum C and D strains produce two types of progenitor toxins, M
      and L. Previously we reported that a 130-kDa nontoxic-nonhemagglutinin (NTNHA)
      component of the M toxin produced by type D strain CB16 was nicked at a unique
      site, leading to a 15-kDa N-terminal fragment and a 115-kDa C-terminal fragment.
      In this study, we identified the amino acid sequences around the nicking sites in
      the NTNHAs of the M toxins produced by C. botulinum type C and D strains by
      analysis of their C-terminal and N-terminal sequences and mass spectrometry. The
      C-terminus of the 15-kDa fragments was identified as Lys127 from these strains,
      indicating that a bacterial trypsin-like protease is responsible for the nicking.
      The 115-kDa fragment had mixtures of three different N-terminal amino acid
      sequences beginning with Leu135, Val139, and Ser141, indicating that 7-13 amino
      acid residues were deleted from the nicking site. The sequence beginning with
      Leu135 would also suggest cleavage by a trypsin-like protease, while the other
      two N-terminal amino acid sequences beginning with Val139 and Ser141 would imply
      proteolysis by an unknown protease. The nicked NTNHA forms a binary complex of
      two fragments that could not be separated without sodium dodecyl sulfate.

PMID- 11233173
TI  - Stability and release requirements of the complexes of GroEL with two homologous
      mammalian aminotransferases.
AB  - The mitochondrial (mAAT) and cytosolic (cAAT) homologous isozymes of aspartate
      aminotransferase are two relatively large proteins that in their nonnative states
      interact very differently with GroEL. MgATP alone can increase the rate of GroEL
      assisted reactivation of cAAT, yet the presence of GroES is mandatory for mAAT.
      Addition of an excess of a denatured substrate accelerates reactivation of cAAT
      in the presence of GroEL, but has no effect on mAAT. These competition studies
      suggest that the more stringent substrate mAAT forms a thermodynamically stable
      complex with GroEL, while rebinding affects the slow reactivation kinetics of
      cAAT with GroEL alone. However, the competitor appears to accelerate the release
      of cAAT from GroEL, most likely by displacing bound cAAT from the GroEL cavity.
      Moreover, cAAT, but not mAAT, shows a time-dependent increase in protease
      resistance while bound to GroEL at low temperature. These results suggest that
      folding and release of cAAT from GroEL in the absence of cofactors may occur
      stepwise with certain interactions being broken and reformed until the protein
      escapes binding. The distinct behavior of these two isozymes most likely results
      from differences in the structure of the nonnative states that bind to GroEL.

PMID- 11233174
TI  - Enzymatic characterization of a novel phospholipase A2 from Crotalus durissus
      cascavella rattlesnake (Maracamboia) venom.
AB  - The PLA2 and crotapotin subunits of crotoxin from Crotalus durissus cascavella
      venom were purified by a combination of HPLC molecular exclusion (Protein Pack
      300SW column) and reverse-phase HPLC (RP-HPLC). Tricine SDS-PAGE showed that the
      PLA2 and crotapotins migrated as single bands with estimated molecular masses of
      15 and 9 kDa, respectively. The amino acid composition of the PLA2 showed the
      presence of 14 half-cysteines and a high content of basic residues (Lys, Arg,
      His), whereas the crotapotins were rich in hydrophobic, negatively charged
      residues and half-cysteines. The PLA2 showed allosteric behavior, with maximal
      activity at pH 8.3 and 35-40 degrees C. The C. d. cascavella PLA2 required Ca2+
      for activity, but was inhibited by Cu2+ and Zn2+ and by Cu2+ and Mg2+ in the
      presence and absence of Ca2+, respectively. Crotapotin (F3) and heparin inhibited
      the catalytic activity of the PLA2 by acting as allosteric inhibitors.

PMID- 11233175
TI  - Resonant recognition model of neuropeptide Y family: hot spot amino acid
      distribution in the sequences.
AB  - The resonant recognition model is used to predict structurally and functionally
      important amino acid residues (so-called hot spots) in the neuropeptide Y (NPY)
      family. Thirty-three polypeptides belong to this family. All of them consist of
      36 amino acids. The model predicts that residues 10 and 28 in the polypeptides
      are hot spots. In the 33 polypeptides, most of the amino acids at residue 10 are
      acidic amino acids, glutamic acid and aspartic acid. Other minor amino acids,
      serine, glycine, and proline, have high probabilities of beta-turn occurrence.
      Amino acids at residue 28 are all branched hydrophobic amino acids, isoleucine,
      leucine, and valine. The profile for predicting hot spots indicates repeating
      patterns of residues 1-18 and residues 19-36. Absolute values at residue i and
      residue i + 18 are the same, but these residues have opposite signs. Therefore
      the model of the NPY family predicts hot spots concerning a combination of
      residue i and residue i + 18.

PMID- 11233176
TI  - Inhibition of octopus glutathione transferase by Meisenheimer complex analog, S
      (2,4,6-trinitrophenyl) glutathione.
AB  - The tight binding of Meisenheimer intermediate with octopus digestive gland
      glutathione transferase was analyzed with 1,3,5-trinitrobenzene, which forms a
      trapped Meisenheimer complex with glutathione because there is no leaving group
      at the ipso carbon. By steady-state enzyme kinetic analysis, an inhibition
      constant of 1.89 +/- 0.17 microM was found for the transient formed, S-(2,4,6
      trinitrophenyl) glutathione. The above inhibition constant is 407-fold smaller
      than the Km value for the substrate (2,4-dinitrochlorobenzene). Thus, S-(2,4,6
      trinitrophenyl) glutathione is considered to be a transition-state analog. The
      tight binding of this inhibitor to the enzyme provides an explanation for the
      involvement of the biological binding effect on the rate enhancement in the
      glutathione transferase-catalyzed SNAr mechanism.

PMID- 11233177
TI  - Analysis of essential leucine residue for catalytic activity of novel
      thermostable chitosanase by site-directed mutagenesis.
AB  - Bacterial chitosanases share weak amino acid sequence similarities at certain
      regions of each enzyme. These regions have been assumed to be important for
      catalytic activities of the enzyme. To verify this assumption, the functional
      importance of the conserved region in a novel thermostable chitosanase (TCH-2)
      from Bacillus coagulans CK108 was investigated. Each of the conserved amino acid
      residues (Leu64, Glu80, Glu94, Asp98, and Gly108) was changed to aspartate and
      glutamine or asparagine and glutamate by site-directed mutagenesis, respectively.
      Kinetic parameters for colloidal chitosan hydrolysis were determined with wild
      type and 10 mutant chitosanases. The Leu64 --> Arg and Leu64 --> Gln mutations
      were essentially inactive and kinetic parameters such as Vmax and kcat were
      approximately 1/10(7) of those of the wild-type enzyme. The Asp98 --> Asn
      mutation did not affect the Km value significantly, but decreased kcat to 15% of
      that of wild-type chitosanase. On the other hand, the Asp98 --> Glu mutation
      affected neither Km nor kcat. The observation that approximately 15% of activity
      remained after the substitution of Asp98 by Asn indicated that the carboxyl side
      chain of Asp98 is not absolutely required for catalytic activity. These results
      indicate that the Leu64 residue is directly involved in the catalytic activity of
      TCH-2.

PMID- 11233178
TI  - [The early history of industrial insulin production in Germany].

PMID- 11233179
TI  - [Molecular pathology of diabetes mellitus. The effects of insulin].

PMID- 11233180
TI  - [From cattle, swine, and horse insulin to human insulin: the biotechnology and
      genetic technology of insulin production].

PMID- 11233181
TI  - [Trust is good, control is better. Glucose tests, insulin syringes, needles].

PMID- 11233182
TI  - [Intensive insulin therapy: results after ten years].

PMID- 11233183
TI  - [Pharmaceutical service to patients with insulin-dependent diabetes mellitus].

PMID- 11233184
TI  - [Insulin formulations].

PMID- 11233185
TI  - [Love for colleges and curriculum].

PMID- 11233186
TI  - Web alert. Microbial genomics.

PMID- 11233187
TI  - BAGECO-6, Florence, 20-24 June 1999.

PMID- 11233188
TI  - On microbes and art: the role of microbial communities in the degradation and
      protection of cultural heritage.

PMID- 11233189
TI  - Clinical progress after randomized on/off pacemaker treatment for hypertrophic
      obstructive cardiomyopathy. Pacing in Cardiomyopathy (PIC) Study Group.
AB  - BACKGROUND: The therapeutic options for hypertrophic obstructive cardiomyopathy
      (HOCM) classically include medical treatment with beta-blockers and calcium
      antagonists or myectomy-myotomy as a surgical possibility for refractory cases.
      The observation that pacemaker activation of the heart in HOCM reduces the
      subaortic gradient is well known but less well investigated. METHODS: Eighty
      three patients (33 female and 50 male) mean age 53 (18-82) years, with symptoms
      refractory to drug treatment and a resting gradient above 30 mmHg, who responded
      favourably to temporary pacing, were included in this prospective study and had a
      pacemaker (DDD) implanted. After an initial double-blind crossover phase of 6
      months, patients were reinvestigated at 12 months and followed for a mean of 36
      months. RESULTS: As observed during a screening investigation, the obstruction
      was significantly reduced from 72 +/- 35 mmHg to 29 +/- 24 mmHg (P < 0.01) when
      the pacemaker was on, while no major effect was seen during the sham phase. The
      effect was persistent at 1 year with a remaining resting gradient of 28 +/- 24
      mmHg. In parallel, we documented an improvement in functional capacity, according
      to the NYHA classification and by quality of life analysis, and a significant
      improvement in dyspnoea and angina. Exercise on treadmill improved only in
      patients with reduced initial tolerance (< 8 min). During the mean follow-up of
      36 months, 65 patients remained on pacing alone, with eight patients having
      additional AV-node ablation and five patients finally having surgery. CONCLUSION:
      This controlled multicentre study shows that pacemaker treatment is an option for
      HOCM patients; it is inoffensive and does not exclude alternative methods, but
      satisfies 79% of patients beyond 3 years.

PMID- 11233191
TI  - Self-assembly of a noncovalently bonded dicopper(II) complex in the solid state
      and in solution.

PMID- 11233192
TI  - Systematic syntheses and structural characterizations of two isomeric
      phosphadicarbaboranes: 6-R-arachno-6,8,9-PC2B7H11 and 6-R-arachno-6,5,7-PC2B7H11.
      The first 10-vertex phosphadicarbaboranes.

PMID- 11233190
TI  - First worldwide clinical experience with a new dual chamber implantable
      cardioverter defibrillator. Advantages and complications. The Ventak AV II DR
      investigators.
AB  - AIMS: The need for physiological pacing and for improving the ability to
      discriminate atrial from ventricular tachyarrhythmias has prompted the
      development of dual chamber implantable cardioverter/defibrillators (ICDs).
      METHODS: Fifty-two patients were implanted with a newly developed dual-chamber
      ICD providing rate-responsive physiological pacing (Ventak AV II DR). The device
      possesses two new arrhythmia detection algorithms ('atrial fibrillation rate
      threshold' and 'ventricular to atrial rate relationship') in addition to commonly
      used features such as 'onset' and 'stability'. During implantation, the atrial
      and ventricular lead impedances and pacing thresholds were determined together
      with the defibrillation threshold. Prior to discharge, attempts were made to
      induce both atrial and ventricular tachyarrhythmias in order to test those new
      detection criteria. All patients were followed for at least 3 months. RESULTS:
      The device was successfully implanted in all 52 patients. Placement of the atrial
      lead was successful in 50/52 patients (96%; P-wave 3.2 +/- 1.4 mV; impedance 576
      +/- 123 omega; atrial pacing threshold 1.2 +/- 0.9 V). Prior to discharge, 32
      episodes of atrial fibrillation (AF) alone, 38 episodes of AF with ventricular
      fibrillation and 10 episodes of AF with monomorphic ventricular tachycardia were
      induced in 33/50 patients (66%) and all were appropriately classified by the
      detection algorithm. During the 3 months follow-up, 12 patients (23%) had
      appropriate and successful therapies for ventricular arrhythmias, while four
      patients (8%) experienced inappropriate ICD therapies. Although all these
      episodes were detected correctly as supraventricular arrhythmias by the device,
      therapy was delivered because of incorrect or incomplete programming. In all
      cases reprogramming of the device resolved the problem. CONCLUSION: Implantation
      of dual chamber ICDs is feasible and appears to improve discrimination of
      supraventricular from ventricular tachyarrhythmias. In addition, patients with
      tachyarrhythmias and concomitant bradyarrhythmias may benefit from simultaneous
      physiological pacing. However, implantation and follow-up of such patients should
      be performed at experienced centres since both surgical handling and programming
      of these devices is more difficult and complex than conventional ICDs.

PMID- 11233194
TI  - A cyanide-bridged chain of Mo6Se8 clusters: a product of cyanide-melt cluster
      synthesis.

PMID- 11233193
TI  - A Co(III) complex in a mixed sulfur/nitrogen ligand environment: modeling the
      substrate- and product-bound forms of the metalloenzyme thiocyanate hydrolase.

PMID- 11233195
TI  - The cubane-type Mo2Ir2S4 cluster containing an organohydrazido(2-) ligand on the
      Mo site.

PMID- 11233196
TI  - Spectroscopic, kinetic, and mechanistic study of a new mode of coordination of
      indole derivatives to platinum(II) and palladium(II) ions in complexes.
AB  - Binding of tryptophan residue to intrinsic metal ions in proteins is unknown, and
      very little is known about the coordinating abilities of indole. Indole-3
      acetamide displaces the solvent ligands from cis-[Pt(en)(sol)2]2+, in which sol
      is acetone or H2O, in acetone solution and forms the complex cis-[Pt(en)(indole-3
      acetamide)]2+ (3) of spiro structure, in which the new bidentate ligand
      coordinates to the Pt(II) atom via the C(3) atom of the indolyl group and the
      amide oxygen atom. This structure is supported by 1H, 13C, 15N, and 195Pt NMR
      spectra and by UV, IR, and mass spectra. Molecular mechanical simulations by
      Hyperchem and CHARMM methods give consistent structural models; the latter is
      optimized by density-functional quantum chemical calculations. Dipeptide-like
      molecules N-(3-indolylacetyl)-L-amino acid in which amino acid is alanine,
      leucine, isoleucine, valine, aspartic acid, or phenylalanine also displace the
      solvent ligands in acetone solution and form complexes cis-[Pt(en) N-(3
      indolylacetyl)-L-amino acid)]2+ (6), which structurally resemble 3 but exist as
      two diastereomers, detected by 1H NMR spectroscopy. The bulkier the amino acid
      moiety, the slower the coordination of these dipeptide-like ligands to the Pt(II)
      atom. The indolyl group does not coordinate as a unidentate ligand; a second
      donor atom is necessary for bidentate coordination of this atom and the indolyl
      C(3) atom. The solvent-displacement reaction is of first and zeroth orders with
      respect to indole-3-acetamide and cis-[Pt(en)(sol)2]2+, respectively. A mechanism
      consisting of initial unidentate coordination of the ligand via the amide oxygen
      atom followed by closing of the spiro ring is supported by 1H NMR data, the
      kinetic effects of acid and water, and the activation parameters for the
      displacement reaction. In the case of N-(3-indolylacetyl)-L-phenylalanine, the
      bulkiest of the entering ligands, the reaction is of first order with respect to
      both reactants. The bidentate indole-3-acetamide ligand in 3 is readily displaced
      by (CH3)2SO and 2-methylimidazole, but not by CNO-, CH3COO-, and CH3CN. Complexes
      cis-[Pd(en)(sol)2]2+ and cis-[Pd(dtco)(sol)2]2+ react with indole-3-acetamide
      more rapidly than their Pt(II) analogues do and yield complexes similar to 3.
      This study augments our recent discovery of selective, hydrolytic cleavage of
      tryptophan-containing peptides by Pd(II) and Pt(II) complexes.

PMID- 11233197
TI  - Influence of H2S and thiols on the binding of alkenes and alkynes to ReS4-: the
      spectator sulfido effect.
AB  - The three-component reaction of ReS4- (1), H2S, and unsaturated substrates (un =
      alkene, alkyne) affords the ReV derivatives Re(S)(S2un)(SH)2-. These adducts
      arise via the addition of H2S to intermediate dithiolates ReS2(S2C2R4)- and
      dithiolenes ReS2(S2C2R2)-. The species [ReS[S2C2(tms)2](SH)2]-,
      [ReS(S2C7H10)(SH)2]- (3), and [ReS(S2C2H4)(SH)2]- are prepared according to this
      route. Similarly, the selenolate-thiolate complex [ReS(S2C7H10)(SeH)(SH)]- (5) is
      produced by the reaction of [ReS2(S2C7H10)]- with H2Se. The corresponding
      reactions using benzenethiol in place of H2S afford the more thermally robust
      adducts [ReS[S2C2(tms)2](SH)(SPh)]-, [ReS(S2C7H10)(SH)(SPh)]- (7), and
      [ReS(S2C2H4)(SH)(SPh)]-. Norbornanedithiolato compounds 3, 5, and 7 are obtained
      as pairs of isomers that differ in terms of the relative orientation of the
      norbornane bridgehead relative to the Re=S unit. The reaction of
      [ReS(S2C7H10)(SD)2]- (3-d2) with H2S to give 3 is proposed to proceed via
      elimination of D2S and subsequent addition of H2S. Variable-temperature 1H NMR
      measurements on the equilibrium of [ReS(S2C6H12)(SPh)(SH)]- with 1,1-hexene, and
      PhSH gave the following results: deltaH = -7 (+/- 1) kJ x mol(-1); deltaS = 23
      (+/- 4) J x mol(-1) x K(-1). Solutions of ethanedithiol and 1 react with C2(tms)2
      and C2H4 to give [ReS[S2C2(tms)2](S2C2H4)]- and [ReS(S2C2H4)2]-, respectively,
      concomitant with loss of H2S. The pathway for the ethanedithiol reaction is
      examined using 2-mercaptoethanol, affording [ReS[S2C2(tms)2](SC2H4OH)]-, which
      does not cyclize. Treatment of a solution of diphenylbutadiyne and 1 with PhSH
      gives two isomers of the dithiolene [ReS(SH)(SPh)[S2C2Ph(C2Ph)]]-. The
      corresponding reaction of ethanedithiol, diphenylbutadiyne, and 1 affords the 1,4
      diphenylbutadiene-1,2,3,4-tetrathiolate complex [[ReS(S2C2H4)]2(S4C4Ph2)]2-.

PMID- 11233198
TI  - Topological ferrimagnetic behavior of two new [Mn(L)2(N3)2]n chains with the new
      AF/AF/F alternating sequence (L = 3-methylpyridine or 3,4-dimethylpyridine).
AB  - The reaction of manganese(II) and pyridine derivatives such as 3-methylpyridine
      (3-Mepy) and 3,4-dimethylpyridine (3,4-Dmepy) led to the new one-dimensional
      systems trans-[Mn(3-Mepy)2(N3)2]n (1) and trans-[Mn(3,4-Dmepy)2(N3)2]n (2).
      Compound 1 crystallizes in the monoclinic system, space group P2(1)/n, a =
      11.201(3) A, b = 14.499(4) A, c = 14.308(4) A, Z = 6, and compound 2 crystallizes
      in the triclinic system, space group P1, a = 11.502(4) A, b = 14.246(5) A, c =
      16.200(8) A, Z = 6. The two compounds show the same general one-dimensional
      arrangement of double azido bridges between neighboring manganese atoms with the
      unprecedented -Mn-(mu(1,3)-N3)2-Mn-(mu(1,3)-N3)2-Mn-(mu(1,1)-N3)2-Mn- sequence.
      Susceptibility and magnetization measurements reveal a ferrimagnetic-like
      behavior derived from the topology of the chain. A model of the Heisenberg chain,
      comprising classical spins coupled through alternating exchange interactions
      J1J1J2... is proposed to describe the magnetic behavior.

PMID- 11233199
TI  - Redox reactivity and reorganization energy of zinc cytochrome c cation radical.
AB  - Little is known about transient intermediates in photoinduced electron-transfer
      reactions of metalloproteins. Oxidative quenching of the triplet state of zinc
      cytochrome c, 3Zncyt, is done at 20 degrees C, pH 7.00, and ionic strength of
      1.00 M, conditions that suppress the thermal back-reaction and prolong the
      lifetime of the cation radical, Zncyt+. This species is reduced by [Fe(CN)6]4-,
      [W(CN)8]4-, [Os(CN)6]4-, [Mo(CN)8]4-, and [Ru(CN)6]4- complexes of similar
      structures and the same charge. The rate constants and thermodynamic driving
      forces for these five similar electron-transfer reactions were fitted to Marcus
      theory. The reorganization energy of Zncyt+ is lambda = 0.38(5) eV, lower than
      that of native cytochrome c, because the redox orbital of the porphyrin cation
      radical is delocalized and possibly because Met80 is not an axial ligand to the
      zinc(II) ion in the reconstituted cytochrome c. The rate constant for electron
      self-exchange between Zncyt+ and Zncyt, k11 = 1.0(5) x 10(7) M(-1) s(-1), is
      large owing to the extended electron delocalization and relatively low
      reorganization energy. These results may be relevant to zinc(II) derivatives of
      other heme proteins, which are often used in studies of photoinduced electron
      transfer reactions.

PMID- 11233200
TI  - Potentiometric and multinuclear NMR study of the binary and ternary uranium(VI)-L
      fluoride systems, where L is alpha-hydroxycarboxylate or glycine.
AB  - Equilibria, structures, and ligand-exchange dynamics in binary and ternary U(VI)
      L-F- systems, where L is glycolate, alpha-hydroxyisobutyrate, or glycine, have
      been investigated in 1.0 M NaClO4 by potentiometry and 1H, 17O, and 19F NMR
      spectroscopy. L may be bonded in two ways: either through the carboxylate end or
      by the formation of a chelate. In the glycolate system, the chelate is formed by
      proton dissociation from the alpha-hydroxy group at around pH 3, indicating a
      dramatic increase, a factor of at least 10(13), of its dissociation constant on
      coordination to uranium(VI). The L exchange in carboxylate-coordinated UO2LF3(2-)
      follows an Eigen-Wilkins mechanism, as previously found for acetate. The water
      exchange rate, k(aq) = 4.2 x 10(5) s(-1), is in excellent agreement with the
      value determined earlier for UO2(2+)(aq). The ligand-exchange dynamics of UO2(O
      CH2-COO)2F3- and the activation parameters for the fluoride exchange in D2O
      (k(obs) = 12 s(-1), deltaH(double dagger) = 45.8 +/- 2.2 kJ mo(-1), and
      deltaS(double dagger) = -55.8 +/- 3.6 J K(-1) mol(-1)) are very similar to those
      in the corresponding oxalate complex, with two parallel pathways, one for
      fluoride and one for the alpha-oxocarboxylate. The same is true for the L
      exchange in UO2(O-CH2-COO)2(2-) and UO2(oxalate)2(2-). The exchange of alpha
      oxocarboxylate takes place by a proton-assisted chelate ring opening followed by
      dissociation. Because we cannot decide if there is also a parallel H+-independent
      pathway, only an upper limit for the rate constant, k1 < 1.2 s(-1), can be given.
      This value is smaller than those in previously studied ternary systems.
      Equilibria and dynamics in the ternary uranium(VI)-glycine-fluoride system,
      investigated by 19F NMR spectroscopy, indicate the formation of one major ternary
      complex, UO2LF3(2-), and one binary complex, UO2L2 (L = H2N-CH2COO-), with
      chelate-bonded glycine; log beta(9) = 13.80 +/- 0.05 for the equilibrium UO2(2+)
      + H2N-CH2COO- + 3F- = UO2(H2N-CH2COO)F3(2-) and log beta(11) = 13.0 +/- 0.05 for
      the reaction UO2(2+) + 2H2N-CH2COO- = UO2(H2N-CH2COO)2. The glycinate exchange
      consists of a ring opening followed by proton-assisted steps. The rate of ring
      opening, 139 +/- 9 s(-1), is independent of both the concentration of H+ and the
      solvent, H2O or D2O.

PMID- 11233201
TI  - Probing the electronic structures of coordination compounds by transient spectral
      hole-burning. Applications to specifically deuterated [Ru(bpy)3]2+ complexes.
AB  - Transient spectral hole-burning (THB), a powerful technique for probing the
      electronic structures of coordination compounds, is applied to the lowest excited
      3MLCT states of specifically deuterated [Ru(bpy)3]2+ complexes doped into
      crystals of racemic [Zn(bpy)3](ClO4)2. Results are consistent with and
      complementary to conclusions reached from excitation-line-narrowing experiments.
      Two sets of 3MLCT transitions are observed in conventional spectroscopy of
      [Ru(bpy-d(n))(3-x)(bpy-d(m))x]2+ (x = 1, 2; n = 0, 2; m = 2, 8; n not = m)
      complexes doped into [Zn(bpy)3](ClO4)2. The two sets coincide with the 3MLCT
      transitions observed for the homoleptic [Ru(bpy-d(m))3]2+ and [Ru(bpy-d(n))3]2+
      complexes and can thus be assigned to localized 3MLCT transitions to the bpy-d(m)
      and bpy-d(n) ligands. The THB experiments presented in this paper exclude a two
      site hypothesis. When spectral holes are burnt at 1.8 K into 3MLCT transitions
      associated with the bpy and bpy-d2 ligands in [Ru(bpy)(bpy-d8)2]2+, [Ru(bpy)2(bpy
      d8)]2+, and [Ru(bpy-d2)2(bpy-d8)]2+, side holes appear in the 3MLCT transitions
      associated with the bpy-d8 ligands approximately 40 and approximately 30 cm(-1)
      higher in energy. Since energy transfer to sites 40 or 30 cm(-1) higher in energy
      cannot occur at 1.8 K, the experiments unequivocally establish that the two sets
      of 3MLCT transitions observed for [Ru(bpy-d(n))(3-x)(bpy-d(m))x]2+ (x = 1, 2)
      complexes in [Zn(bpy)3](ClO4)2 occur on one molecular cation.

PMID- 11233202
TI  - Cobalt-complexed conjugated diyne salts: a family of rigid masked
      dielectrophiles. Syntheses, structures, and double nucleophilic substitutions.
AB  - A family of dicationic diyne salts of the general formula [(Co2(CO)6)2
      mu,eta2,eta2-(Nu-CH2C(triple bond)C-C(triple bond)CCH2-Nu)][BF4]2 [Nu = SMe2 (3);
      Nu = NC6H7, 3-picoline, (5); Nu = NC9H7, quinoline (7)] were prepared and fully
      characterized. Three X-ray molecular structures of 3, 5, and the neutral starting
      material 2,4-hexadiyne-1,6-diol complex [(Co2(CO)6)2-mu,eta2,eta2-(HO-CH2C(triple
      bond)C-C(triple bond)CCH2-OH)] (1) are presented. Complex 1 crystallizes in the
      triclinic space group P1 with a = 14.722(2) A, b = 14.571(3) A, c = 14.722(2) A,
      alpha = 105.17(1) degrees, beta = 113.30(1) degrees, gamma = 99.20(1) degrees,
      and Z = 4. Complex 3 crystallizes in the monoclinic space group P2(1)/n with a =
      12.758(3) A, b = 13.360(3) A, c = 20.494(3) A, beta = 91.44(1) degrees, and Z =
      4, and compound 5 also crystallizes in the monoclinic space group P2(1)/n with a
      = 9.426(2) A, b = 21.739(5) A, c = 18.704(3) A, beta = 94.86(1) degrees, and Z =
      4. The X-ray structures provide us with valuable information on the arrangement
      of the Co2-alkyne units, which have a cis geometry and are in sharp contrast to
      that observed generally for diyne-tetracobalt compounds. Complex [(Co2(CO)6)2
      mu,eta2,eta2-(Me2S-CH2C(triple bond)C-C(triple bond)CCH2-SMe2)][BF4]2 (3) reacts
      with N-, S-, and P-centered nucleophiles and affords the related substituted
      complexes in high yields. The stability and reactivity of the disulfonium diyne
      complex 3 toward nucleophiles are compared to those of the analogous disulfonium
      yne complex [(Co2(CO)6)2-mu,eta2,eta2-(Me2S-CH2-C(triple bond)C-CH2-SMe2)][BF4]2
      (4).

PMID- 11233203
TI  - Unusual electronic effects of electron-withdrawing sulfonamide groups in
      optically and magnetically active self-assembled noncovalent heterodimetallic d-f
      podates.
AB  - The segmental ligand 2-(6-(N,N-diethylcarbamoyl)pyridin-2-yl)-1,1'-dimethyl-2'-(5
      (N,N-diethylsulfonamido)-pyridin-2-yl)-5,5'-methylenebis[1H-benzimidazole] (L3)
      is synthesized via a multistep strategy that allows the selective introduction of
      an electron-withdrawing sulfonamide group into the ligand backbone and its
      subsequent hydrolysis to the hydrophilic sulfonate group. Compared to that of the
      methylated analogue L1, the affinity of the bidentate binding unit of L3 for H+
      and for trivalent lanthanide ions (LnIII) in [Ln(L3)3]3+ and [Ln2(L3)3]6+ is
      reduced because the electron-withdrawing sulfonamide substituent weakens sigma
      bonding, but improved retro-pi-bonding between the bidentate binding units of L3
      and soft 3d-block ions (M(II) = FeII, ZnII) overcomes this effect and leads to
      homometallic complexes [Mn(L(i))m]2n+ (i = 1, 3) displaying similar stabilities.
      Theoretical ab initio calculations associate this dual effect with a global
      decrease in energy of pi and sigma orbitals when the sulfonamide group replaces
      the methyl group, with an extra stabilization for the LUMO (pi). The reaction of
      L3 with a mixture of LnIII and M(II) (M = Fe, Ni, Zn) in acetonitrile gives the
      noncovalent podates [LnM(L3)3]5+ in which LnIII is nine-coordinated by the three
      wrapped tridentate segments, while the bidentate binding units provide a facial
      pseudooctahedral site around M(II). The X-ray structure of
      [EuZn(L3)3](ClO4)4(PF6)(CH3NO2)3(H2O) reveals that the bulky sulfonamide group at
      the 5-position of the pyridine ring only slightly increases the Zn-N bond
      distances as a result of sigma/pi compensation effects. The introduction of
      spectroscopically and magnetically active FeII and NiII into the pseudooctahedral
      site allows the detailed investigation of the electronic structure of the
      bidentate segment. Absorption spectra, combined with electrochemical data,
      experimentally demonstrate the dual effect associated with the attachment of the
      sulfonamide group (decrease of the sigma-donating ability of the pyridine lone
      pair and increase of the pi-accepting properties of the coordinated bidentate
      binding unit). The influences on the ligand field strength and on tunable room
      temperature FeII spin-crossover processes occurring in [LnFe(L3)3]5+ are
      discussed, together with the origin of the entropic control of the critical
      temperature in these thermal switches.

PMID- 11233205
TI  - Formation and characterization of water-soluble hydrido-ruthenium(II) complexes
      of 1,3,5-triaza-7-phosphaadamantane and their catalytic activity in hydrogenation
      of CO2 and HCO3- in aqueous solution.
AB  - The water-soluble tertiary phosphine complex of ruthenium(II), [RuCl2(PTA)4],
      (PTA = 1,3,5-triaza-7-phosphaadamantane) was used as catalyst precursor for
      hydrogenation of CO2 and bicarbonate in aqueous solution, in the absence of amine
      or other additives, under mild conditions. Reaction of [RuCl2(PTA)4] and H2 (60
      bar) gives the hydrides [RuH2(PTA)4] (at pH = 12.0) and [RuH(PTA)4X] (X = Cl- or
      H2O) (at pH = 2.0). In presence of excess PTA, formation of the unparalleled
      cationic pentakis-phosphino species, [HRu(PTA)5]+, was unambiguously established
      by 1H and 31P NMR measurements. The same hydrides were observed when
      [Ru(H2O)6][tos]2 (tos = toluene-4-sulfonate) reacted with PTA under H2 pressure.
      The rate of CO2 hydrogenation strongly depends on the pH. The highest initial
      reaction rate (TOF = 807.3 h(-1)) was determined for a 10% HCO3-/90% CO2 mixture
      (pH = 5.86), whereas the reduction was very slow both at low and high pH (CO2 and
      Na2CO3 solutions, respectively). 1H and 31P NMR studies together with the kinetic
      measurements suggested that HCO3- was the real substrate and [RuH(PTA)4X] the
      catalytically active hydride species in this reaction. Hydrogenation of HCO3-
      showed an induction period which could be ascribed to the slow formation of the
      catalytically active hydride species.

PMID- 11233204
TI  - Tripodal peptide hydroxamates as siderophore models. Iron(III) binding with
      ligands containing H-(alanyl)n-beta-(N-hydroxy)alanyl strands (n = 1-3) anchored
      by nitrilotriacetic acid.
AB  - Combining three units of one of H-(alanyl)n-beta-(HO)alanyl peptides (n = 1-3)
      with nitrilotriacetic acid affords tripodal peptide hydroxamate ligands (1L, 1D,
      2LL, 2DL, and 3LLL, where each L or D denotes the L- or D-alanyl residue). These
      ligands form six-coordinate octahedral complexes (Fe-1L, Fe-1D, Fe-2LL, Fe-2DL,
      and Fe-3LLL) with iron(III) in aqueous near neutral pH solution, and the
      stability and the chirality of the complexes formed depend on the alanyl residues
      incorporated. Thus Fe-2LL is the most stable against attack of H+ and OH- ions
      and the least labile in the iron(III) removal by EDTA. The CD spectra show a
      predominance of the A configuration for Fe-1D, Fe-2LL, Fe-2DL, and Fe-3LLL, but
      the opposite delta configuration for Fe-1L. These ligands and their gallium(III)
      complexes are studied by 1H NMR spectroscopy in DMSO-d6 solution. CD and NMR
      spectral analysis, aided by molecular model examinations, indicates that critical
      factors in controlling the configuration and the stability of the complexes are
      (1) the hydroxamate-carrying alanyl residue, (2) the expanse of an interior space
      in the ligand, and (3) an interstrand amide NH hydrogen bond; the latter bonding
      is possible with ligands 2LL and 2DL. A microbial growth promotion activity test
      shows that ligands 1L, 2LL, and 3LLL all act as iron-transporting agents.

PMID- 11233206
TI  - Thiocyanogen as an intermediate in the oxidation of thiocyanate by hydrogen
      peroxide in acidic aqueous solution.
AB  - The kinetics of the reaction of H2O2 with excess SCN- in acidic media was studied
      by use of Ti(IV) as an indicator for the concentration of H2O2. Pseudo-first
      order behavior was realized by this method, and these data confirm the acid
      catalyzed rate law and rate constant reported some 40 years ago for this reaction
      under conditions of excess H2O2. Under the same conditions except without Ti(IV),
      repetitive-scan spectra reveal the formation and decay of an intermediate that
      absorbs in the UV. In the proposed mechanism, HOSCN is produced in the first step
      and it is converted rapidly to (SCN)2 through its equilibrium reaction with SCN-.
      The observed intermediate is believed to be (SCN)2, which decays on a longer time
      scale. Excellent global fits of this mechanism to the repetitive-scan data are
      obtained with rate constants constrained by the Ti(IV) data and published
      previously in our study of the ClO2/SCN- reaction. These fits yield a spectrum
      for (SCN)2 that is characterized by lambda(max) = 297 nm and epsilon297 = 147 M(
      1) cm(-1), in fine agreement with our prior report.

PMID- 11233207
TI  - Crystal structure and magnetic properties of an octacyanometalate-based three
      dimensional tungstate(V)-manganese(II) bimetallic assembly.
AB  - A single crystal of the title compound [MnII6(H2O)9[W(V)(CN)8]4 x 13H2O]n was
      synthesized in a hot aqueous solution containing octacyanotungstate, Na3[W(CN)8]
      x 3H2O, and Mn(ClO4)2 x 6H2O. The compound crystallized in the monoclinic system,
      space group P2(1)/c with cell constants a = 15.438(2) A, b = 14.691(2) A, c =
      33.046(2) A, beta = 94.832(9) degrees, and Z = 4. The crystal consists of a W(V)
      CN-MnII linked three-dimensional network [[MnII(H2O)]3[MnII(H2O)2]3[W(V)(CN)8]4]n
      and H2O molecules as crystal solvates. There are two kinds of W sites: one is
      close to a dodecahedron geometry with six bridging and two terminal CN ligands;
      the other is close to a bicapped trigonal prism with seven bridging and one
      terminal CN ligands. The field-cooled magnetization measurement showed that the
      compound exhibits a spontaneous magnetization below Tc = 54 K. Further
      magnetization measurements on the field dependence reveal it to be a ferrimagnet
      where all of the MnII ions are antiparallel to all the W(V) ions.

PMID- 11233208
TI  - Structural and electronic characterization of
      nitrosyl(octaethylporphinato)iron(III) perchlorate derivatives.
AB  - The synthesis and crystallographic characterization of the five-coordinate
      iron(III) porphyrinate complex [Fe(OEP)(NO)]ClO4 are reported. This [FeNO]6
      complex has a nearly linear Fe-N-O group (angle = 173.19(13) degrees) with a
      small off-axis tilt of the Fe-N(NO) vector from the heme normal (angle = 4.6
      degrees); the Fe-N(NO) distance is 1.6528(13) A and the iron is displaced 0.32 A
      out-of-plane. The complex forms a tight cofacial pi-pi dimer in the solid state.
      Mossbauer spectra for this derivative as well as for a related crystalline form
      are measured both in zero applied magnetic field and in a 7 T applied field. Fits
      to the measurements made in applied magnetic field demonstrate that both
      crystalline forms of [Fe(OEP)(NO)]ClO4 have a diamagnetic ground state at 4.2 K.
      The observed isomer shifts (delta = 0.22-0.24 mm/s) are smaller than those
      typically observed for low-spin iron(III) porphyrinates. Analogous Mossbauer
      measurements are also obtained for a six-coordinate derivative,
      [Fe(OEP)(Iz)(NO)]ClO4 (Iz = indazole). The observed isomer shift for this species
      is smaller still (delta = 0.02 mm/s). All derivatives show a strong temperature
      dependence of the isomer shift. The data emphasize the strongly covalent nature
      of the FeNO group. The Mossbauer isomer shifts suggest formal oxidation states
      greater than +3 for iron, but the NO stretching frequencies are not consistent
      with such a large charge transfer to NO. Differences in the observed nitrosyl
      stretching frequencies of the two crystalline forms of [Fe(OEP)(NO)]ClO4 are
      discussed.

PMID- 11233209
TI  - Kinetic and mechanistic study with optically active, four-coordinate nickel(II)
      complexes: stereoselectivity in ligand substitution.
AB  - Conventional and rapid scan stopped-flow spectrophotometry as well as polarimetry
      was used to study the kinetics of ligand substitution in six chiral bis N
      alkylsalicylaldiminato nickel(II) complexes NiA2 by different chiral salen-type
      ligands H2B, according to NiA2 + H2B --> NiB + 2HA, in acetone at 298 K and,
      partly, at variable temperature. In most cases ligand substitution was found to
      follow monophasic second-order kinetics, rate = k x [NiA2] x [H2B]. Second-order
      rate constant k, lying in the range 10(-2)-400 M(-1) s(-1) at 298 K, was
      determined for the various combinations of enantiomers in a given system
      NiA2/H2B, namely, R-NiA2/R-H2B, S-NiA2/R-H2B, R-NiA2/S-H2B, and S-NiA2/S-H2B. It
      was found that ligand substitution is subject to chiral discrimination. The ratio
      of second-order rate constants, kfast/kslow, with kfast being rate constant k for
      the faster reacting pair of enantiomers and vice versa, lies in the range 1.0
      3.0, depending on the nature of the N-alkyl groups in NiA2 and organic groups
      attached to the ethylene bridge in the salen ligands H2B. The rate discrimination
      factor of 3.0, as obtained for NiA2 = bis[N
      dehydroabietylsalicylaldiminato]nickel(II) reacting with the R- and with the S
      enantiomer of H2B = N,N'-disalicylidene-1,2-diamino-4-methylpentane, appears to
      be the highest stereoselectivity reported so far for ligand substitution in
      nickel(II) complexes. With NiA2 = R- and S-bis[N-(1-phenylethyl)-5
      nitrosalicylaldiminato]nickel(II) and H2B = R- and S-N,N-disalicylidene-1,2
      diamino-4-methylpentane, the kinetics of ligand substitution are biphasic,
      describing initial adduct formation between NiA2 and H2B (equilibrium constant K)
      and stepwise loss of the two bidentate ligands HA (first-order rate constants k1
      and k2). The data for K, k1, and k2 for one of the combinations of enantiomers
      were determined at variable temperature, and the corresponding activation
      parameters are presented.

PMID- 11233210
TI  - Synthesis and characterization of a polycarbon organometallic cluster,
      [PPN]2[Fe6(CO)18C4].
AB  - The polycarbon metal cluster [Fe6(CO)18C4]2- is formed by the reaction of
      CF3SO3SO2CF3 with [Fe3(CO)9(CCO)]2-. Apparently, the SO2CF3 moiety abstracts an
      oxygen from the ketenylidene (CCO) ligand and C-C coupling occurs to form the C4
      ligand. A single-crystal X-ray structure determination reveals that the pattern
      of C-C bond lengths of the C4 ligand in [Fe6(CO)18C4]2- mimic those in free
      butadiene.

PMID- 11233211
TI  - Coordination polymers of copper(I) halides.
AB  - A total of 21 complexes of CuX (X = Cl, Br, I) with bridging ligand (B = 4,4'
      dipyridyl (Bpy), pyrazine (Pyz), quinoxaline (Quin), phenazine (Phz), 1,4
      diazabicyclo[2.2.2]octane (DABCO), and hexamethylenetetramine (HMTA)) have been
      synthesized. The products show two stoichiometries: [CuXB] (type 1) and [(CuX)2B]
      (type 2). Both types can be obtained for B = Bpy, depending on the conditions of
      preparation. In these cases, the type 2 stoichiometry is the kinetic product.
      Type 2 complexes only are found for B = Pyz (X = I), Quin, Phz, DABCO, and HMTA.
      Type 1 complexes form for Pyz (X = Cl, Br). Thermogravimetic analyses of the
      complexes reveal the general decomposition trend: 1 --> 2 --> [(CuX)2B(1/2)] -->
      CuX. The X-ray crystal structure of [CuBr(Pyz)] (type 1) features copper atoms
      bridged by Br and Pyz, forming 2D sheets of fused rectangular Cu4Br2(Pyz)2 units.
      The X-ray structure of [(CuI)2(Quin)] (type 2) shows 2D layers composed of
      [Cu2I2]infinity "stair step" chains which are cross-linked by Quin ligands. A
      total of 16 complexes of CuXL (L = P(OPh)3) with bridging ligand (B = those above
      and 1,4-dimethylpiperazine (DMP)) have also been prepared. All of these products,
      except those of HMTA, are of type 3 formulation, [(CuXL)2B]. The HMTA products
      have the formula [CuX(HMTA)], type 4. Thermal decomposition of the type 3 and 4
      complexes occurs with initial loss of B, L, or both. The X-ray structures of
      [(CuBrL)2(Bpy)] and [(CuBrL)2(Pyz)] (type 3) reveal 1D chains formed from
      rhomboidal (LCu)2Br2 units linked by the B ligand. The type 4 structure of
      [CuBrL(HMTA)] is shown by X-ray to be a simple halide-bridged dimer.

PMID- 11233213
TI  - The first structurally alternating copper(II) chain with alternate single end-on
      and end-to-end azido bridging: a synthesis, crystal structure, and low
      temperature magnetic study.

PMID- 11233212
TI  - Structural diversity in solvated lithium aryloxides. Syntheses, characterization,
      and structures of [Li(OAr)(THF)x]n and [Li(OAr)(py)x]2 complexes where OAr =
      OC6H5, OC6H4(2-Me), OC6H3(2,6-(Me))2, OC6H4(2-Pr(i)), OC6H3(2,6-Pr(i)))2, OC6h4(2
      Bu(t)), OC6H3(2,6-Bu(t)))2.
AB  - A series of sterically varied aryl alcohols H-OAr [OAr = OC6H5 (OPh), OC6H4(2-Me)
      (oMP), OC6H3(2,6-(Me))2 (DMP), OC6H4(2-Pr(i)) (oPP), OC6H3(2,6-(Pr(i)))2 (DIP),
      OC6H4(2-Bu(t)) (oBP), OC6H3(2,6-(Bu(t)))2 (DBP); Me = CH3, Pr(i) = CHMe2, and
      Bu(t) = CMe3] were reacted with LiN(SiMe3)2 in a Lewis basic solvent
      [tetrahydrofuran (THF) or pyridine (py)] to generate the appropriate
      "Li(OAr)(solv)x". In the presence of THF, the OPh derivative was previously
      identified as the hexagonal prismatic complex [Li(OPh)(THF)]6; however, the
      structure isolated from the above route proved to be the tetranuclear species
      [Li(OPh)(THF)]4 (1). The other "Li(OAr)(THF)x" products isolated were
      characterized by single-crystal X-ray diffraction as [Li(OAr)(THF)]4 [OAr = oMP
      (2), DMP (3), oPP (4)], [Li(DIP)(THF)]3 (5), [Li(oBP)(THF)2]2, (6), and
      [Li(DBP)(THF)]2, (7). The tetranuclear species (1-4) consist of symmetric cubes
      of alternating tetrahedral Li and pyramidal O atoms, with terminal THF solvent
      molecules bound to each metal center. The trinuclear species 5 consists of a six
      membered ring of alternating trigonal planar Li and bridging O atoms, with one
      THF solvent molecule bound to each metal center. Compound 6 possesses two Li
      atoms that adopt tetrahedral geometries involving two bridging oBP and two
      terminal THF ligands. The structure of 7 was identical to the previously reported
      [Li(DBP)(THF)]2 species, but different unit cell parameters were observed.
      Compound 7 varies from 6 in that only one solvent molecule is bound to each Li
      metal center of 7 because of the steric bulk of the DBP ligand. In contrast to
      the structurally diverse THF adducts, when py was used as the solvent, the
      appropriate "Li(OAr)(py)x" complexes were isolated as [Li(OAr)(py)2]2 (OAr = OPh
      (8), oMP (9), DMP (10), oPP (11), DIP (12), oBP (13)) and [Li(DBP)(py)]2 (14).
      Compounds 8-13 adopt a dinuclear, edge-shared tetrahedral complex. For 14,
      because of the steric crowding of the DBP ligand, only one py is coordinated,
      yielding a dinuclear fused trigonal planar arrangement. Two additional structure
      types were also characterized for the DIP ligand: [Li(DIP)(H-DIP)(py)]2 (12b) and
      [Li2(DIP)2(py)3] (12c). Multinuclear (6,7Li and 13C) solid-state MAS NMR
      spectroscopic studies indicate that the bulk powder possesses several Li
      environments for "transitional ligands" of the THF complexes; however, the py
      adducts possess only one Li environment, which is consistent with the solid-state
      structures. Solution NMR studies indicate that "transitional" compounds of the
      THF precursors display multiple species in solution whereas the py adducts
      display only one lithium environment.

PMID- 11233214
TI  - Synthesis and characterization of monomeric oxo dichloro 1,3-dialkyl p-tert
      butylcalix[4]arene complexes of molybdenum(VI,V) and tungsten(VI,V).

PMID- 11233215
TI  - X-ray evidence of CN bridging in bimetallic complexes based on [M(CN)8]4- (M =
      Mo, W). The crystal structure of [[Mn(bpy)2]2(mu-NC)2[Mo(CN)6]2(mu
      CN)2[Mn(bpy)2]2].8H2O.

PMID- 11233216
TI  - (THF)3LiCl as a ligand for low-coordinate Fe(II): crystal structure of
      [(Me3Si)2N]2Fe(-Cl)Li(THF)3.

PMID- 11233217
TI  - Synthesis of a clathrochelate complex with an appended pyridine and its
      coordination to a cobaloxime complex.

PMID- 11233218
TI  - Group 6 metallocalixarenes bearing "hydrazido(2-)" groups.

PMID- 11233219
TI  - Unexpected synthesis of an 8-shaped macrocycle instead of an interlocking-ring
      system.

PMID- 11233220
TI  - Emotional reactions to the sudden death of a child: the challenge to emergency
      care providers.
AB  - The death of a child has the potential to traumatize everyone involved. Child
      deaths caused by auto crashes, suicides, murders, gun accidents, drowning, fires,
      natural disasters, sudden illness, and other events trigger painful and profound
      emotional grief reactions in family members, and, at times, for emergency care
      providers. What grief reactions do family members experience when their child
      dies suddenly? What emotional struggles take place with siblings? How do
      emergency care providers cope with the tragic and painful deaths of children? We
      are guided by the literature and by our own experiences in pediatric emergency
      departments in trying to supply answers to the questions posed.

PMID- 11233221
TI  - [Doppler ultrasonographic evaluation of circulation in hyperplastic prostate].
AB  - From 1997 to 1999 transrectal ultrasonic dopplerography was used for examination
      of 10 healthy controls and 57 patients with prostatic hyperplasia. The findings
      allow to characterize anatomically and functionally vascular structure of the
      prostate and adjacent tissues in health, hyperplasia, after open and
      transurethral operative interventions. The role of dopplerography in decision
      making on the treatment policy in prostatic hyperplasia was studied.
      Retrospective analysis of the case records provided dopplerographic prognostic
      signs of intraoperative and early postoperative bleedings. This served the basis
      for development of additional dopplerographic criteria for choice of surgical
      policy in prostatic hyperplasia. Thus, the role of transrectal dopplerography is
      determined not only in diagnosis but also in the treatment of hyperplastic
      prostate.

PMID- 11233222
TI  - [Reserve capacities of blood coagulation and total lytic activities in patients
      with benign prostatic hyperplasia].
AB  - Prior to and after the double local arm hypoxia test, whole blood
      thromboelastography under lowered contact activation was used to examine
      hemostasis and total blood lytic activity in 27 males aged 59-68 years who had
      moderate benign prostatic hyperplasia (BPH) as assessed by the International
      Scale. The control group included 25 apparently healthy males. Only 40.7% of
      patients were found have adequate reserve capacities of the study systems. BPH
      induced tension of reserve capacities of total blood lytic activity in 37% of
      cases and their depletion in 22.3%, even then moderate symptoms of the disease
      occurred.

PMID- 11233223
TI  - [Changes in serum levels of lipid peroxidation products and ceruloplasmin in
      patients with benign prostatic hyperplasia in uncomplicated and complicated
      periods after transurethral electro-resection].
AB  - Lipid peroxidation products and ceruloplasmin in the serum were measured in 78
      patients with benign prostatic hyperplasia (BPH) in uncomplicated or complicated
      period after transurethral resection of the prostate (TUR) and before it. In
      uncomplicated period, a short rise in lipid peroxidation activity and lowering of
      ceruloplasmin concentrations were followed by normalisation by day 6. In the
      complicated postoperative period by day 6 these indices were higher. The authors
      propose that these indices are used in assessment of antioxidants efficacy after
      TUR for BPH.

PMID- 11233224
TI  - [Role of biochemical methods in follow-up and treatment of patients with
      urolithiasis].
AB  - 4-6-year follow-up using different tests covered 15 patients with urolithiasis
      and 11 control subjects aged 25 to 66 years. All the patients underwent 1 to 5
      sessions of extracorporeal lithotripsy and one patient underwent open surgery.
      Clinical and biochemical findings on the groups were compared to the evidence of
      Litos test. Initiation of antirecurrence therapy should be based on the
      information gained with different methods, primarily, biochemical. Follow-up of
      the patients including biochemical control over their metabolic condition must be
      conducted for at least 5 years.

PMID- 11233225
TI  - [Extracorporeal shock-wave lithotripsy of bladder stones in patients with benign
      prostatic hyperplasia].
AB  - In urological department of Moscow Regional Research Clinical Institute,
      extracorporeal shock-wave lithotripsy (ECSWL) or bladder stones in patients with
      benign prostatic hyperplasia (BPH) has been made prior to TUR from 1991. This
      treatment was given to 52 patients aged 54-79 years with prostatic volume 40-120
      cm3. Complete or partial fragmentation of the vesical calculi was achieved after
      1 to 3 ECSWL sessions (a total of 105 sessions, 2000-3000 impulses a session).
      Pretreatment with ECSWL of bladder stones significantly facilitates TUR in BPH
      patients with vesical calculi of big size (2.5 cm and more in diameter).
      Extracorporeal fragmentation of large stones prior to TUR makes surgery of such
      patients less traumatic and reduces the risk of intraoperative complications
      compared to endoscopic cystolithotripsy or cystolithotomy. ECSWL of cystolithes
      expands indications for drug therapy or thermal non-endoscopic BPH treatment in
      aged patients with poor somatic status and in young sexually active males
      rejecting surgery.

PMID- 11233226
TI  - [Chronic obstructive prostatitis].
AB  - The authors review current classifications of chronic prostatitis and propose
      their own classification which reflects routes of prostatic infection, division
      of infectious prostatitis into obstructive and non-obstructive forms, etiology of
      chronic prostatitis. Original methods and facilities for prostatic drainage via
      transurethral and transrectal approaches are described.

PMID- 11233227
TI  - [Hyperbaric oxygenation in the treatment of patients with chronic congestive
      prostatitis and lower fertility].
AB  - Due to deteriorated demographic indices in the country, male infertility is a
      highly pressing problem. Chronic prostatitis is one of its causes. Hyperbaric
      oxygenation was used to affect male genital microcirculation, thus improving the
      spermatic morphological and functional characteristics. Positive effects of the
      method are ascribed not only to better microcirculation, but also to improved
      redox processes in spermatogenesis.

PMID- 11233229
TI  - [Modification of meatoglanuloplasty (MAGPI-Duckett) for treatment of balanic and
      coronal forms of hypospadia in children].
AB  - 14 boys with balanic hypospadia (BH) and 23 boys with coronal hypospadia (CH)
      aged 9 months to 15 years were operated in 1997-2000. For 13 boys this operation
      was meatoglanuloplasty (MAGPI) by J. Duckett. Complications occurred in 4 boys:
      retraction (downwards) of the meatus (n = 2), urethral stenosis and urinary
      fistula (n = 2). 24 boys have undergone modified MAGPI operation. The
      modification consists in extended mobilization of the lateral parts of the head
      with longitudinal consecutive incisions along the head margin into the spongy
      bodies. The head is closed by suturing its mobilized margins with two rows of
      interrupted monofilamentous (PDS, prolene) sutures above the urethra. A variant
      of saving foreskin is possible when partial separation of the internal and
      external layers is made bilaterally with consecutive circular closure of the
      preputial sac. Phimosis is prevented by a relief longitudinal incision along the
      internal foreskin and transverse suturing. The patients were followed up for 2
      months to 1.5 years. The original operation MAGPI provided good cosmetic and
      functional results in 9 boys(69.2%), satisfactory in 2 boys(15.4%),
      unsatisfactory also in 2 boys(15.4%). The modified MAGPI operation provided only
      good cosmetic and functional results. Thus, the proposed modification (MAGPI
      Duckett) ensures a more reliable variant of meatoglanuloplasty in balanic and
      coronal hypospadia irrespective of the size and shape of the head, presence of
      the scaphoid fossa or meatostenosis. These additional procedures helped to reduce
      the number of postoperative complications and improved cosmetic and functional
      results.

PMID- 11233228
TI  - [Omnic (tamsulosin) in the treatment of benign prostatic hyperplasia].

PMID- 11233230
TI  - [Immunity status in early postoperative complications in children with anomalies
      of kidneys and upper urinary tract].
AB  - 31 children aged 1 to 9 years with malformations of the kidneys and upper urinary
      tracts were preoperatively examined for immune status. After plastic operation 14
      children developed early postoperative infectious-inflammatory complications. It
      is suggested that early postoperative complications in some children with renal
      and upper urinary tract maldevelopments may arise because of weak compensatory
      abilities and immunodeficiency resultant from the operative stress. These created
      favourable conditions for activation of latent infection. Immunological
      assessment of the patient prior to surgery predicts early postoperative
      complications and thus enables proper preventive measures.

PMID- 11233231
TI  - [Percutaneous intrarenal ultrasonography].
AB  - In vivo and in vitro experiments were made to study percutaneous intrarenal
      ultrasonography (PIU). The transurethral ultrasonic probe (5.5 MHz, 1850
      "Bruel&Kjer, Denmark) was inserted through the nephrostomic fistula in the
      dilated pelvis with the tubus of the nephroscope K. Storz 27093B. Scanning of the
      cavitary renal system and ureteropelvic zone was conducted by moving the probe in
      the longitudinal and transverse directions. The experiment on 21 removed kidneys
      investigated potentialities of PIU in hydronephrotic transformation caused by
      ureteropelvic stricture (4 kidneys), urolithiasis (7 kidneys), carcinoma of renal
      parenchyma (5 kidneys), pelvic cancer (1 kidney), combined renal cell and
      epithelial renal carcinoma (1 kidney); in pyonephrosis (1 kidney) and contracted
      kidney (2 kidneys). 43 patients (19 males and 24 females aged 7 to 63 years) have
      undergone PIU in the course of percutaneous nephrolithotripsy (n = 23),
      percutaneous endopyelotomy (n = 15) and percutaneous endoresection of solitary
      renal cyst (n = 5). PIU accurately localizes residual and x-ray-negative
      concrement fragments raising the effectiveness of percutaneous nephrolithotripsy,
      precisely differentiates internal renal structures, visualizes pelvic wall,
      vessels and tissues of the renal sinus, provides additional information about
      ureteropelvic zone and its changes. PIU can find wide application in
      intraoperative diagnosis of different renal and upper urinary tract diseases.

PMID- 11233232
TI  - [Anatomo-functional state of parenchyma in early renal cancer].

PMID- 11233233
TI  - [Memorable dates in the history of urology and allied sciences in 2001].

PMID- 11233235
TI  - Cost-effectiveness associated with the diagnosis and staging of non-small-cell
      lung cancer.
AB  - OBJECTIVE: We evaluated how much time and money could be saved without
      compromising overall results in treating lung cancer. SUBJECTS AND METHODS: We
      retrospectively evaluated 318 patients for T- and M-factors and 335 for N-factor.
      If bronchoscopy failed to diagnose a mass lesion believed to be malignant in x
      ray computed tomography (CT), we proceeded to direct thoracotomy without needle
      or video-assisted biopsy. When mediastinal nodes were negative in CT, we
      proceeded to direct thoracotomy without mediastinoscopy. We searched routinely
      for distant metastasis with brain and abdominal CTs and bone scans. RESULTS:
      Lesions suspected of malignancy in CT were pathologically malignant in 93%. A
      total of 82.8% of patients with CT-negative mediastinum were without metastasis.
      The remainder, with metastasis, had a postoperative 5-year survival of 23.5%.
      Brain CT scans were positive in only 2.2%, abdominal CT scans in 2.4%, and bone
      scans in 5.0%, for patients with a cT1/T2 non-cN2 lesion. CONCLUSION: Brain and
      abdominal CT scans and bone scans may be omitted for cT1/T2 and non-cN2 lesions
      in CT. CT-negative mediastinum then leads to direct thoracotomy. The vast
      majority of patients may thus undergo surgery earlier with less physical and
      financial burden. The cost saving was calculated to be 59.4% per cT1/T2 non-cN2
      patient, or US$666,815, for population evaluated based on cost-effectiveness.

PMID- 11233234
TI  - [Effectiveness of various alfuzosin schedules in patients with benign prostatic
      hyperplasia (BPH)].
AB  - 238 patients with initial BPH (mean age 64.07 years) were treated with alfusosine
      in a standard dose 5 mg twice a day for 6 months. After that 117 patients
      continued the above scheme while 121 patients continued to receive alfusosine in
      the same dose each other day. The results assessed by IPSS, QOL, maximal urine
      flow rate, levels of prostate-specific antigen in the serum appeared identical in
      both groups. Thus, the split course of alfusosine after 6-month standard therapy
      is perspective as it is more cost effective than the standard scheme being
      equally beneficial.

PMID- 11233236
TI  - The role of neoadjuvant radiochemotherapy using low-dose fraction cisplatin and 5
      fluorouracil in patients with carcinoma of the esophagus.
AB  - OBJECTIVE: We clarified the role of neoadjuvant radiochemotherapy in patients
      with carcinoma of the esophagus and compared it to neoadjuvant chemotherapy.
      METHODS: We retrospectively examined 40 patients diagnosed with advanced thoracic
      esophageal carcinoma who underwent neoadjuvant therapy followed by esophagectomy
      between 1993 and 1999. We divided them into 2 groups: radiochemotherapy (17) and
      chemotherapy (23). Radiochemotherapy patients underwent 40 Gy radiation and low
      dose fraction cisplatin (7 mg/body/day, 5 days a week x 4 weeks) and 5
      fluorouracil (350 mg/body/day x 28 days). Chemotherapy patients received high
      dose fraction cisplatin/5-fluorouracil involving 2 courses of cisplatin (70
      mg/m2/day on day 1) and 5-fluorouracil (700 mg/m2/day on days 1-5). RESULTS:
      Complete pathological response was 17.6% in the radiochemotherapy group and 0% in
      the chemotherapy group respectively. No hospital mortality occurred in the
      radiochemotherapy group, and 1 of the 23 chemotherapy patients died in the
      hospital due to postoperative complications. The incidence of residual tumors was
      significantly higher in the chemotherapy group (34.8%) than in the
      radiochemotherapy group (0%). Actuarial survival in the radiochemotherapy group
      at 1 year was 80.2% and at 3 years 53.5%. Actuarial survival in the chemotherapy
      group at 1 year was 56.5% and at 3 years 30.4%. CONCLUSIONS: Histological
      effectiveness was greater in patients treated with preoperative radiochemotherapy
      than those treated with preoperative chemotherapy. The combination of radiation
      and low-dose fraction CDDP/5-FU thus is first choice in neoadjuvant
      radiochemotherapy for the advanced esophageal carcinoma.

PMID- 11233237
TI  - Effects of lung metastasectomy on respiratory function.
AB  - OBJECTIVE: The effects of lung metastasectomy on respiration were evaluated.
      SUBJECTS: From 1961 to 1999, 203 patients underwent lung metastasectomy. Of
      these, 102 patients who had undergone only partial lung resection, had undergone
      sufficient respiratory function testing, and had not suffered from other lung
      disease were included. RESULTS: Unilateral thoracoscopic surgery caused less
      decrease in percent vital capacity than surgery through a posterolateral
      thoracotomy, in both the early (rate of decrease: 16.2 +/- 9.1 vs. 33.0 +/-
      12.0%, p < 0.01), and the late postoperative period (2.0 +/- 4.5 vs. 17.8 +/-
      6.0%, p < 0.0001). Two thoracoscopic operations caused less decrease in percent
      vital capacity than 2 operations through a posterolateral thoracotomy (21.3 +/-
      13.8 vs. 61.1 +/- 8.1%, p = 0.02). Bilateral metastasectomy through a median
      sternotomy caused less decrease in percent vital capacity than that through
      posterolateral thoracotomies (45.5 +/- 13.7 vs. 60.8 +/- 8.8%, p < 0.05). Four
      (36%) of 11 patients who had undergone 3 or more metastasectomies exhibited
      dyspnea of degree 3 or higher on the Hugh-Jones classification. CONCLUSIONS:
      Thoracoscopic metastasectomy and metastasectomy through a median sternotomy
      caused less restrictive respiratory dysfunction than metastasectomy through a
      posterolateral thoracotomy. Since metastatic lung disease often necessitates
      repeated metastasectomy, and repeated metastasectomy often causes severe
      restrictive respiratory dysfunction, metastasectomy should be performed with a
      less invasive procedure.

PMID- 11233239
TI  - Development of a tracheal stapling device.
AB  - OBJECTIVE: Recent years have witnessed a multitude of technical advances
      regarding gastrointestinal and vascular anastomosis. However, difficulties still
      hamper tracheal and bronchial anastomosis. We have therefore developed a novel
      set of instruments and performed end-to-end anastomosis of the transected canine
      cervical trachea to establish the operative procedures. METHODS: A novel set of
      instruments was developed for tracheal anastomosis including two pairs of forceps
      for grasping the free tracheal ends, a metal connecting device, and clamping
      forceps for staple insertion. Briefly, the operative procedure involves fixation
      of forceps circumferentially to hold the cut trachea. End-to-end anastomosis is
      completed by joining the forceps with a clamp and stapling the tracheal ends
      everted outward. End-to-end anastomosis of the cervical trachea was performed on
      23 dogs. Animals were monitored on a daily basis, and bronchofiberscopy was
      performed periodically. Deaths from all causes were evaluated by immediate
      necropsy. Sixteen dogs were sequentially sacrificed at 1, 2, 3 and at 6 months
      after surgery. RESULTS: In our dog model, stenosis at the anastomosis of the
      cervical trachea was found as a complication in 8 of 23 cases. Tracheal rupture
      occurred in a further 3 cases, slight granulation in another 4, and the remaining
      8 showed no complication. Histological findings of anastomotic healing were
      similar to those reported for hand suture.

PMID- 11233238
TI  - Platelet activation and aggregation during normothermic cardiopulmonary bypass.
AB  - OBJECTIVE: The usefulness of heparin-bonded circuits under normothermic
      cardiopulmonary bypass has not been elucidated. We studied platelet activation
      and aggregation differences between heparin-bonded and nonheparin-bonded circuits
      in patients undergoing surgery involving normothermic cardiopulmonary bypass.
      METHODS: Eight patients underwent coronary artery bypass grafting with non
      heparin-bonded circuits (controls) and 7 the same with heparin-bonded circuits
      (heparin group). Heparin bonding was applied to the blood contact surface of our
      system, including the oxygenator and connecting tubes. Patient body temperature
      was kept between 36 and 37 degrees C. Beta-thromboglobulin and platelet factor 4
      were measured before, during, and after cardiopulmonary bypass, and platelet
      aggregation was evaluated by laser-light scattering. RESULTS: Changes in beta
      thromboglobulin and platelet factor 4 during and after cardiopulmonary bypass
      were similar in both groups. Small particle formation was the primary aggregate
      induced during and after cardiopulmonary bypass in both groups, and serial
      changes in particle formation up to 24 hours after cardiopulmonary bypass were
      similar in both groups. CONCLUSIONS: Our results indicate that in 2-3 hours of
      normothermic cardiopulmonary bypass, heparin-bonded circuits are similar to
      nonheparin-bonded ones in platelet compatibility.

PMID- 11233240
TI  - Thymoma. Analysis of prognostic factors.
AB  - OBJECTIVE: We evaluated the prognostic factors for thymoma that remain
      controversial. METHODS: We studied 72 consecutive patients treated for thymoma
      during the period between 1966 and 1997. Recurrence-free interval rates and
      overall survival rates calculated by the Kaplan-Meier method were compared using
      log-rank test by the Masaoka stage, extent of surgical resection, histology, or
      associated disease(s). Multivariate analysis was performed using Cox's
      proportional hazards model. RESULTS: Thirty-two thymomas were at Masaoka stage I,
      9 at stage II, 15 at stage III, and 16 were at stage IV. There were 56 complete
      resections, 7 incomplete resections (2 at stage III and 5 at stage IV), and 9
      biopsies (1 at stage III and 8 at stage IV). Forty-one thymomas were cortical, 16
      medullary, and 15 were mixed form. Association of myasthenia gravis was found in
      20 patients, and pure red cell aplasia in 7. After an average follow-up period of
      103 months, the recurrence-free 5-, 10-, 15-year interval rate was 89%, 80%, 80%,
      respectively, and overall 5-, 10-, 15-year survival rate was 86%, 71%, 59%,
      respectively. Factors influencing the recurrence-free interval and overall
      survival included the Masaoka stage, extent of surgical resection, and
      association with pure red cell aplasia. Multivariate analysis revealed stage IV
      tumor and association with pure red cell aplasia as risk factors for recurrence.
      Pure red cell aplasia indicated poor prognosis for overall survival. CONCLUSIONS:
      Masaoka stage, extent of surgical resection, and association with pure red cell
      aplasia were prognostic factors for thymoma. Multidisciplinary treatment for
      stage IV tumors and better control of pure red cell aplasia, if associated,
      should be investigated.

PMID- 11233241
TI  - Concomitant replacement of the aortic root and aortic arch with or without
      secondary thoracoabdominal aorta replacement.
AB  - OBJECTIVES: Extensive aortic replacement, such as concomitant aortic root and
      arch replacement, thoracoabdominal aortic repair, and complete thoracic aorta
      replacement, remains controversial. We studied surgical morbidity and mortality
      in patients undergoing concomitant aortic root and arch replacement, and those
      undergoing secondary replacement of the thoracoabdominal aorta after this
      preceding procedure. SUBJECTS AND METHODS: Between January, 1987 and March 1999,
      21 patients (mean age: 52 years) underwent concomitant aortic root and arch
      replacement involving 3 surgical procedures--aortic root replacement with
      composite graft and arch (n = 12), aortic root replacement with valve sparing and
      arch (n = 4), or aortic root replacement with composite graft and arch and
      elephant trunk (n = 5). RESULTS: Overall hospital mortality was 4.8%. Six
      patients (mean age: 42 years) underwent secondary thoracoabdominal aorta
      replacement after the concomitant root and arch procedure. The mean time until
      secondary surgery was 9.5 months. There was 1 hospital death. CONCLUSION:
      Concomitant replacement of the aortic root and arch, or secondary replacement of
      the thoracoabdominal aorta after concomitant root and arch replacement can be
      conducted with low surgical morbidity and mortality.

PMID- 11233242
TI  - Cardio-aortic operation in octogenarians.
AB  - OBJECTIVE: Aging of the population is a current phenomenon in Japan, and life
      expectancy at 80 years old is getting longer. So we reviewed cardio-aortic
      operations on octogenarians at our institution. SUBJECTS AND METHODS: Thirty
      three consecutive octogenarian patients who had undergone cardio-aortic
      operations from 1992 to 1998 were studied. There were 14 men and 19 women. The
      mean age was 81.9 years. Of the 33, 19 patients (58%) were in New York Heart
      Association class IV, and 21 patients (64%) were operated on urgently or in
      emergency. The procedures undergone were operation for coronary artery disease in
      17 patients, operation for valvular disease in 7 patients, operation for thoracic
      aorta in 7 patients, and others in 2 patients. RESULTS: The hospital mortality
      rate was 27% (9 patients). However, 89% of patients experiencing hospital death
      were in New York Heart Association class IV preoperatively and had required an
      emergency/urgent operation. On the other hand, there was only one hospital death
      (1/12, 8.3%) among the elective patients. The statistically significant risk
      factors for hospital death were renal insufficiency, shock, New York Heart
      Association class IV, intra-aortic balloon pumping, and longer cardiopulmonary
      bypass time. The one-, three-, and five-year-survival rate was 73%, 68%, and 55%,
      respectively. Of the survivors, 77% were in class I or II. CONCLUSION: Although
      octogenarians' hospital mortality was still very high, the mid-term results were
      acceptable and the survivors' quality of life was satisfactory. These data
      suggested that we should operate on cardio-aortic patients before they reach a
      very serious state, especially in octogenarians.

PMID- 11233243
TI  - Obliterative airway disease and graft stenting in pig-to-dog tracheal
      xenotransplantation.
AB  - OBJECTIVE: Obliterative airway disease occurring in concordant tracheal
      xenografts in rodent models is histologically similar to obliterative
      bronchiolitis in human lung allografts. We studied whether obliterative airway
      disease would occur in a large animal-discordant model. METHODS: Pig and dog
      tracheas were cryopreserved for 7 to 14 days, and 18 recipient dogs given
      splenectomy 7 days before transplantation, then seven tracheal rings were removed
      and a corresponding five-ring donor tracheal segment was transplanted to the
      excised site. Grafts were wrapped with pedicled omentum and inmmunosuppression
      was conducted with tacrolimus or deoxyspergualin. Graft status was observed by
      bronchoscopy. Dogs were classified into three groups. Group 1 consisted of dog-to
      dog allotransplantation animals (control group, n = 5), Group 2 of pig-to-dog
      xenotransplantation animals (n = 8), and Group 3 of pig-dog xenotransplantation
      animals who also underwent graft stenting immediately after transplantation (n =
      5). RESULTS: Grafts healed well in 4 of 5 Group 1 dogs. Tracheal stricture began
      on day 5 post transplantation and the lumen was obstructed by fibrosis by days 8
      to 14 in all Group 2 dogs. All Group 3 dogs remained in good respiratory status
      until death. CONCLUSION: Obliterative airway disease developed quickly in pig-to
      dog discordant tracheal xenografts. Graft stenting is a feasible treatment for
      managing of tracheal obstruction.

PMID- 11233244
TI  - Survival and sinus rhythm maintenance after modified Cox/maze procedure and
      mitral valve operation in patients with chronic atrial fibrillation.
AB  - OBJECTIVE: Sinus rhythm gained after the Cox/maze procedure concomitant with
      mitral valve operation has demonstrated long-term attrition during the follow-up,
      no information exists on whether the type of mitral valve operation--(repair vs.
      replacement)--affects this sinus rhythm maintenance rate. We retrospectively
      studied patients undergoing concomitant mitral valve operation and Cox/maze
      procedure to answer this question. METHODS: Between April 1993 and August 1995,
      87 consecutive patients--35 men and 52 women (mean age: 59.3 years)--with chronic
      atrial fibrillation and mitral valve disease underwent the modified Cox/maze
      procedure and concomitant mitral valve operation, with 56 having mitral valve
      repair (repair group) and 31 mitral valve replacement (replacement group).
      Patients were followed up and changes in rhythm studied retrospectively. RESULTS:
      Follow-up for a mean 51.3 +/- 11.6 months was completed in 82 of 83 long-term
      survivors (99%). Repair group surgery survival was 98.1 +/- 1.9% at 1 year and
      94.2 +/- 3.2% at 5 based on the Kaplan-Meier method. Replacement group surgery
      survival was 85.7 +/- 5.9% at 1 year and 82.9 +/- 6.4% at 5. Probability in sinus
      rhythm maintenance for the repair group at 1 year was 88.6 +/- 5.4% and at 5
      years was 67.6 +/- 9.1%. Probability in sinus rhythm maintenance for the
      replacement group at 1 year was 95.7 +/- 4.3% and at 5 years was 65.0 +/- 11.1%.
      CONCLUSIONS: Medium-term results after the Cox/maze III procedure concomitant
      with mitral valve operation are good. The attrition of sinus rhythm maintenance
      appears similar by the completion of 5-year follow-up.

PMID- 11233245
TI  - Surgical treatment for a ruptured thoracic aortic aneurysm.
AB  - OBJECTIVE: The treatment for a ruptured thoracic aortic aneurysm remains
      controversial. This study was undertaken to assess the outcome from surgery.
      METHODS: Between 1993 and 1998, we have performed 19 operations for a ruptured
      thoracic aortic aneurysm. Patients with an impending rupture or a chronic false
      aneurysm were excluded. There were 11 men and 8 women, with a mean age of 70.5 +/
      6.7 years. The aneurysm was caused by dissection in 8 patients. Of these, 7 were
      acute (Stanford type A, 6; type B, 1), and the other one was chronic (type B).
      Aortic rupture occurred into the pericardial cavity (n = 7), into the left lung
      (n = 6), the mediastinum (n = 3), the pleural cavity (n = 2), or into the
      esophagus (n = 1). Severely unstable hemodynamics were noted in 12 patients with
      a rupture into the pericardium, mediastinum, or pleural cavity (Group A).
      Inotropic support was required in each of these patients. Metabolic acidosis
      developed all but 1 patient. The 7 patients with a rupture into the lung or
      esophagus coughed or vomited blood (Group B). The operative approach was anterior
      (n = 17) or lateral (n = 2). Grafts were placed in the ascending aorta (n = 4),
      ascending and transverse arch aorta (n = 7), transverse arch aorta (n = 3), or in
      the descending thoracic aorta (n = 5). Selective cerebral perfusion was used in
      13 patients. RESULTS: There were 5 hospital deaths (26.3%). The postoperative
      complications included central nervous system dysfunction (n = 3), low cardiac
      output syndrome or cardiac arrhythmias (n = 3), respiratory failure (n = 4),
      acute renal failure (n = 1), and local or systemic infections (n = 4). The
      perioperative event-free rate was 36.8% overall, 25% in Group A, and 57.1% in
      Group B. CONCLUSIONS: Patients with unstable hemodynamics require prompt
      operative intervention. Rupture into the esophagus is associated with a high
      mortality rate. Rupture in a thoracic aortic aneurysm can be successfully treated
      with emergency surgery.

PMID- 11233246
TI  - Off-pump coronary artery bypass. Mid-term results.
AB  - OBJECTIVES: Off-pump coronary artery bypass grafting (CABG) on the beating heart
      has become popular procedure in cardiac surgery and its initial results appeared
      favorable. We report our early and mid-term results of off-pump CABG performed at
      Shin-Tokyo Hospital. METHODS: Medical records of patients undergoing off-pump or
      conventional on-pump CABG from September 1, 1996, to August 31, 1999 were
      retrospectively reviewed. Patients underwent off-pump CABG were further
      classified into 2 groups; MIDCAB (Off-pump CABG for single vessel
      revascularization via a small skin incision) and OPCAB (off-pump CABG mainly
      approached via midline sternotomy) group. Their preoperative, perioperative, and
      follow-up data were collected and analyzed. RESULTS: Among a total of 995 cases
      of CABG, 194 cases were off-pump CABG (male/female 142/52, mean age 66.9). The
      mean number of distal anastomoses in off-pump CABG was 1.9 +/- 0.9 (1.0 +/- 0.0
      in MIDCAB and 2.3 +/- 0.7 in OPCAB), which was significantly fewer than in on
      pump CABG (3.6 +/- 1.1), with p < 0.0001. Intubation time (5.3 +/- 5.7 hours in
      off-pump CABG vs 13.1 +/- 24.2 hours in on-pump CABG), ICU stay (1.7 +/- 1.1 vs
      3.2 +/- 3.0 days), and postoperative hospital stay (14.0 +/- 7.9 vs 18.1 +/- 12.1
      days) in off-pump CABG were significantly shorter than in on-pump CABG (p <
      0.0001). In the off-pump CABG group, there were no in-hospital deaths and 14
      major complications, fewer than in on-pump CABG (8 hospital deaths and 114 major
      complications). Postoperative angiography before hospital discharge was conducted
      in 80 patients (41.2%) and showed 2 occlusions, giving a graft patency rate of
      98.6% in the off-pump group. During follow-up (0.9 +/- 0.6 year) period, there
      were 5 non-cardiac deaths and 20 cardiac events in the off-pump group. The
      actuarial survival rate at 36 months was 94.6% for off-pump CABG, showing no
      significant difference from the rate for conventional CABG patients (95.2% at 36
      month, p = NS) The event-free rate was 84.0% at 36 months in off-pump CABG
      patients; however, which was less favorable than on-pump CABG patients (88.0% at
      36 months, p < 0.05). CONCLUSIONS: Both in-hospital and mid-term results for off
      pump CABG patients were acceptable. Isolated CABG can thus be safely performed
      without cardiopulmonary bypass. Advances in coronary stabilization have
      contributed to these improved results. The observed long-term cardiac events may
      be related to incomplete revascularization.

PMID- 11233247
TI  - Saccular aneurysm in the left main coronary artery.
AB  - The patient was a 70-year-old male with a chief complaint of chest pain. Coronary
      angiography revealed a saccular aneurysm of 11 mm in diameter at the furcation of
      the left main coronary artery. Triple vessel disease was also seen. At surgery,
      it was judged that the risk to rupture of the aneurysm was high because the
      aneurysmal wall was very thin. Therefore, the blood flow into the aneurysm was
      blocked, and coronary artery bypass grafting was performed. In a pathological
      study on the aneurysmal wall, no atherosclerotic and no inflammatory changes were
      found, but acidic mucopolysaccharides were detected in the tunica media. Coronary
      aneurysms with coronary stenosis in the elderly have been reported to be
      arteriosclerotic without exception. Here we present this rare case of a left main
      coronary artery aneurysm with coronary stenosis in an old-aged patient,
      considered to be due to metabolic abnormalities in the smooth muscle cells.

PMID- 11233248
TI  - Minimally invasive coronary artery bypass grafting surgery in a child with
      Kawasaki disease.
AB  - An 8-year-old girl with Kawasaki disease underwent surgical revascularization to
      the left anterior descending coronary artery on the beating heart via a left
      anterior short thoracotomy. Angiography 21 months after surgery showed excellent
      graft patency. This case--the first success in minimally invasive surgical
      coronary artery revascularization in a child in the world--suggests that
      minimally invasive methods are a reasonable alternative in coronary artery
      revascularization in a child with Kawasaki disease whose left anterior descending
      artery is the only requiring it.

PMID- 11233249
TI  - Surgically treated aortic root aneurysm following aortic valve replacement.
AB  - A 65-year-old man with aortic regurgitation underwent aortic valve replacement
      with a St. Jude Medical prosthetic valve about 6 years ago. At that time, the
      aortic root was slightly dilated at about 40 mm in diameter and the ascending
      aorta was within the normal range. This year, the man was diagnosed with an
      aortic root aneurysm in regular follow-up echocardiography. Chest-enhanced
      computed tomography and chest aortography at our hospital demonstrated a pear
      like aortic root aneurysm about 60 mm in diameter. Elective operation for the
      aortic root aneurysm was conducted September 29, 1999, based on the Bentall
      procedure. Composite graft replacement with coronary reconstruction was conducted
      using a 28-mm Hemashield prosthetic graft and a 23-mm St. Jude Medical prosthetic
      valve under cardiopulmonary bypass. An 8-mm Hemashield graft was interposed on
      the left main coronary artery and the right coronary artery was directly
      anastomosed using a Carrel patch method. The postoperative course was uneventful
      and post-operative examination demonstrated good surgical results. Histological
      findings of the aortic aneurysm wall showed cystic medial necrosis. Surgical
      cases of aortic root aneurysm after aortic valve replacement are rare, but
      serious complications with the possibility of rupture or dissection warrant
      surgical intervention.

PMID- 11233250
TI  - [Boris Ivanovich Tkachenko (on his 70th birthday)].

PMID- 11233251
TI  - [Venous circulation physiology in works by B. I. Tkachenko (on his 70th
      birthday)].

PMID- 11233252
TI  - [Primed in situ labelling of human metaphase chromosomes].
AB  - Primed in situ labelling (PRINS) contributes to the elucidation of the
      organization of eukaryotic chromosomes and provides an alternative way to
      localize gene on chromosomes. Here we present the results of random primer and
      SOX degenerate primer PRINS on human metaphase chromosomes. The particular band
      pattern of dark and light was observed by using random primer PRINS. SOX
      degenerate primer PRINS revealed more SOX gene loci and proved further that SOX
      genes were not clustered on human chromosomes.

PMID- 11233253
TI  - [Analysis of HLA-DQB1 polymorphism by PCR-SSO in Yichu of Yunnan Province].
AB  - HLA-DQB1 genes from 76 individuals of Yichu ethnic group in Yunnan Province were
      investigated, using PCR-SSO genotyping method. Of the 38 DQB1 alleles detected,
      DQB1 * 0301 (gene frequency: 36.18%-36.84%) was the most common gene. The
      frequencies of DQB1 * 0502(10.53%-11.18%), DQB1 * 0401 (9.21%), DQB1 * 0302(8.55%
      9.21%), DQB1 * 0601(7.89%), DQB1 * 05031(6.58%), and DQB1 * 03032(5.92%-6.58%)
      are more than 5%. While DQB1 * 0504, DQB1 * 0604, DQB1 * 06052, DQB1 * 0606, DQB1
      * 0607, DQB1 * 0608, DQB1 * 06112, DQB1 * 0613, DQB1 * 0615, DQB1 * 0203, DQB1 *
      0305, DQB1 * 0306, DQB1 * 0307, and DQB1 * 0308 were not observed. Comparison of
      HLA-DQB1 allele frequencies of Yichu with those of 13 other Chinese ethnic groups
      showed some significant differences, suggesting Yichu is unique in the
      distribution of HLA alleles.

PMID- 11233254
TI  - [The study of genetic variability of mtDNA in common laboratory inbred strains of
      mice].
AB  - The genetic variation of mtDNA among 7 common laboratory inbred strains of mice
      was analyzed by PCR-RFLP and PCR-SSCP techniques. D-loop, tRNA(Met + Glu + Ile)
      and ND3 fragments of mtDNA from the mices showed no variation in 46 endonuclease
      sites; Deeply analyzed by PCR-SSCP, the D-loop 5' fragment and 3' fragment of
      mtDNA from these mice also show no genetic variation. Because of maternal mode of
      inheritance of mtDNA, the results indicate that only one female lineage
      contributed to the formation of all these common inbred strains of mice.

PMID- 11233255
TI  - [Construction of a deep coverage rice BAC library and identification of clones
      associated with disease-resistant genes].
AB  - A BAC library for IRBB56, an accession pyramiding Xa4, xa5 and xa13 three
      bacterial blight resistance genes, was constructed. The library contains 55,296
      clones with an average insert size of 132 kb. Based on a haploid genome size of
      450 Mb, the coverage of the library was about 14 genome equivalents that make it
      one of the most comprehensive BAC libraries available in rice and provide 99.99%
      possibility to isolate any interested rice genes or sequences in the library. To
      determine the representation of organelle DNA homologues in the library, the
      library was screened with three different chloroplast genes and four
      mitochondrial genes, respectively. Results from this screening showed that less
      than 1% of clones in the library contain organelle genomic DNA homologues. Then,
      DNA markers on three different chromosomes linked to Xa4, xa5, and xa13, and a
      PCR fragment of rice UROD gene, were used to screen the library resulting in a
      range of 11-106 hits that will promote the isolation of these genes. The deep
      coverage and the large insert size of the library will facilitate physical
      mapping, isolation, and cloning of rice genes.

PMID- 11233256
TI  - [Mapping genes for rice CMS-WA fertility restoration].
AB  - In a population consisting of 227 test-crosses of Zhenshan 97A x (Zhenshan 97B x
      Milyang 46) F6, a linkage map of 115 RFLP markers was constructed and employed to
      detect QTL for rice CMS-WA (wild abortive cytoplasmic male sterility) fertility
      restoration. One QTL having major effect, qRf-10, and 3 QTL having minor effects,
      qRf-1, qRf-7 and qRf-11, were detected. The four genes mainly acted additively
      with each other, but epistasis was also evident. Two minor QTL, qRf-1 and qRf-11,
      were significantly interacted with the major gene qRf-10. It was also found that
      interaction effects among minor QTL varied greatly depending on whether qRf-10
      was present. Two other QTL, qSF-1 and qSF-7, were detected, which did not display
      any effects on fertility restoration. Instead, they showed effects for increasing
      SF when qRf-10 was present.

PMID- 11233257
TI  - [QTL analysis for epistatic effects and QTL x environment interaction effects on
      final height of rice (Oryza sativa L.)].
AB  - QTLs with epistatic effects and environmental interaction effects for final
      height of rice were studied by mixed-model based QTL mapping with a doubled
      haploid population from IR64/Azucena in four environments. The results
      demonstrated the importance of epistasis as a genetic basis of the quantitative
      traits and also revealed several important features of this phenomenon. In the
      results, 100 per cent of QTLs were involved in epistasis, of which 64 per cent
      were found with significant additive effects. This might mean that the usual
      estimates of the QTL additive effects could be confounded by epistatic
      interactions and result in biased estimation unless epistatic effect is
      separated. The other 36 per cent did not have any significant additive effects of
      their own but were involved in 48 per cent of the identified epistatic
      interactions. Such loci might play the role of modifying agents that tend to
      activate other loci or modify the action of other loci. The other features of
      epistasis include as follows: it was fairly common for the same locus to get
      involved in interactions with more than one locus; the QTLs with relatively high
      magnitude of effects might also be involved in epistasis; and epistasis was
      sensitive to environmental interactions for their expression. QTL x environment
      (QE) interaction effects were detected more often than QTL main effects for plant
      height behavior, as might indicate that gene expression could be greatly affected
      by environments.

PMID- 11233258
TI  - [Differential accumulation of the new high-affinity phosphate transporter
      candidated gene fragment in rice roots in response to phosphorus deficiency
      stress].
AB  - Phosphate is a major constraint to crop production, and phosphate uptake in plant
      is mainly by high-affinity phosphate transporter under phosphate deficiency
      condition. Using RT-PCR, a 1,178 bp phosphate transporter gene fragment OjPT1 was
      cloned from roots of Jingxi17 (Oryza sativa L. ssp. japanica) supplied with no
      phosphate. The comparison of this sequence with ones in GenBank indicated that it
      shared about 70% similarity at amino acid level with other phosphate transporters
      in higher plants, such as Arabidopsis thaliana, potate, tamato, Medicago
      truncatula and Catharanthus roseus, and high similarity with phosphate
      transporters in Saccharomyces cerevisiae and Neurospora crassa. RT-PCR assay
      showed that the OjPT1 transcripts were induced under phosphate deficiency
      condition. This gene fragment OjPT1 has been deposited in GenBank (accession No.
      AF249619).

PMID- 11233259
TI  - [Genetic analysis and gene deduction of powdery mildew resistance in T. durum-Ae.
      squarrosa amphidiploids].
AB  - Eleven seedlings with resistance and two amphidiploids with disease resistance at
      all developmental stage were screened by using No. 15 isolate of E. graminis f.
      sp. tritici to inoculate 99 T. durum-Ae. squarrosa amphidiploids. The two
      amphidiploids with disease resistance at all developmental stage, M53 and M81,
      and their Ae. squarrosa parents were resistant to No. 15 isolate of powdery
      mildew payhogen, but their T. durum parents were susceptible. Therefore, the
      powdery mildew resistance of M53 and M81 were derived from Ae. squarrosa.
      Amphidiploid M74, which had the same durum parent as M53 but different Ae.
      squrrosa parent, was susceptible to No. 15 isolate in adult stage. M29 and M35,
      which had the same durum parent as M81 but different Ae. squarrosa parent were
      susceptible in all stage. These results were also proved that the powdery mildew
      resistance genes were derived from Ae. sqarrosa. Genetic analysis showed that
      powdery mildew resistance gene in M53 or M81 was a single dominant gene. A series
      of lines with known powdery mildew resistance genes and two unknown lines were
      used to test response patterns with 14 differential isolates of E. graminis f.
      sp. tritici. The response patterns in M53 and M81 were different from Pm1 to Pm21
      and indicated that M53 and M81 conferred a new powdery mildew resistance gene
      respectively.

PMID- 11233260
TI  - [RAPD analysis of the genome evolution in allopolyploid species in Aegilops].
AB  - RAPD analysis was performed by applying a set of 24 arbitrary primers to all the
      allopolyploids and their diploid progenitors in Aegilops L. The analysis based on
      313 RAPD fragments revealed that the allopolyploids carrying D genome grouped
      with Ae. squarrosa (DD) in one cluster. The allopolyploids carrying U genome
      grouped with Ae. umbellulata (UU) in another cluster except Ae. juvenalis
      (DDMMUU), which grouped with Ae. squarrosa (DD). The allopolyploids did not
      cluster with the other diploids. The results indicated that the allopolyploids
      shared close relationship with Ae. squarrosa (DD) and Ae. umbellulata (UU),
      respectively. It proved that the D and U genomes altered relatively little from
      the diploid progenitors after the allopolyploids came into being, but the other
      genomes changed greatly.

PMID- 11233261
TI  - [Comparative studies of mitochondrial DNA of T-type cytoplasmic male sterile
      lines and their maintainers in wheat].
AB  - mtDNAs of T type wheat cytoplasmic male sterile lines 75-3369A and their
      maintainers 75-3369B were isolated and digested completely with restriction
      endonuclease BamH I, EcoR I, Hind III. The mitochondrial genomic difference
      between CMS line and maintainers were revealed by Southern hybridization with
      probes of atp6 from Oenothera and nad3/rps12, cox I from wheat mitochondria.
      Southern hybridization showed the differences between these two lines. Discussion
      was made on the change of the DNA composition and the male sterile cytoplasm.

PMID- 11233262
TI  - [Microsatellite marker analysis of a soybean recombinant inbred line NJRIKY].
AB  - The prerequisite of genomic research such as genetic mapping is construction of a
      suitable segregating population and its reasonable evaluation before use. A
      recombinant inbred line (RILs), NJRIKY, was constructed through a cross between
      Kefeng 1 and Nannong 1138-2. The present study was focused on evaluation of
      genetic structure of the RILs through the simple sequence repeats (SSRs)
      analysis. A total number of 138 pairs of SSRs primers covering the whole soybean
      genome were randomly selected for polymorphic analysis between two parents. 86
      pairs of which were polymorphic and polymorphic rate is up to 62.32%. 90
      polymorphic loci were found. Further analysis with polymorphic SSRs loci on the
      sampled lines indicated that not only segregation of most SSRs loci conformed to
      the ratio of 1:1, but also almost each sampled line tended to homozyge. The
      distribution of genotypic composition was normal. The population is ideal for
      genetic mapping and other genomic research.

PMID- 11233263
TI  - [Major gene plus poly-gene inheritance of erucic acid content in Brassica napus
      L].
AB  - Inheritance of erucic acid content in the cross of HSTC14 x Ningyou 7 (Brassica
      napus L.) was investigated by applying the major gene plus poly-gene model of
      quantitative traits to a joint analysis of multi-generations (P1, F1, P2, B1:2
      B2:2 and F2:3). The results showed that erucic acid content in the cross of
      HSTC14 x Ningyou 7 was controlled by two major genes with additive-dominance
      epistatic effects plus polygenes with additive-dominance effects (the E-1 model).
      Heritability values of the major genes of B1:2, B2:2 and F2:3 population were
      estimated as 69.47%, 28.25% and 51.33% respectively, while those of polygene were
      29.81%, 70.39% and 47.86%. This results demonstrated that erucic acid content
      level in the cross was mainly controlled by two major genes mixed with the effect
      of polygenes. The estimated additive effects of the two major genes, da and db,
      were -12.1712 and -6.5423 respectively. The dominant effect of the first major
      gene was 9.1011, much higher than that of the second one. The interaction effect
      of the first major gene's additive effect and the second major gene's dominance
      effect was 22.4400, while that between the second major gene's additive effect
      and the first major gene's dominance effect was only 1.0317. There were obvious
      differences in genetic effects between the two major genes. The effect of db was
      only about 53.75% that of da, indicating that the contributions to erucic acid
      level of the two major genes was not equal in the cross. The possible reasons
      resulting in the difference was discussed in this paper.

PMID- 11233264
TI  - [Cloning and function of sanJ--a gene involved in nikkomycins biosynthesis of
      Streptomyces ansochromogenes].
AB  - A 7.5 kb DNA fragment was identified from the cosmid library of Streptomyces
      ansochromogenesus using a partial DNA fragment involved in the nikkomycin
      biosynthesis as a probe. It was cloned into pBluescript M13- and the resulting
      recombinant plasmid was designated as pNL2200. The nucleotide sequence of 2.3 kb
      Sal I -BamH I DNA fragment was determined and analysed. The result indicated that
      the fragment contains one complete open reading frame (ORF); The start codon is
      GTG at 271 position and the stop codon is TGA at 1,954 position. It contains
      1,686 base pairs and encodes a protein with 561 amino acids. The deduced product
      has 44% identity with the ligase belong to the superfamily of adenylate-forming
      enzyme. The experiment of gene disruption showed that the sanJ gene was closely
      related to nikkomycins biosynthesis of Streptomyces ansochromogenes. It was
      designated as sanJ.

PMID- 11233265
TI  - [Mitochondrial DNA sequence variations of Zhuang ethnic group in Guangxi].
AB  - The mtDNA hypervariable segment I sequences (515bp) were sequenced in 83 Zhuangs
      from Gunngxi Province, with the aim to learn more about the origin and genetic
      structure of the current Zhuangs. 66 haplotypes were identified in the samples,
      with 71 sites showing polymorphism. Phylogenetic analysis of the 66 haplotypes
      suggests that there are geographic differentiation in current Zhuangs, and those
      from the 4 geographic regions (Nanning, Hechi, Baise and Liuzhou) have different
      distribution frequencies in the cluster I, II and III in the tree. More than 50%
      individuals from Liuzhou and Hechi converge into cluster II, while those from
      Nanning and Baise have high frequency in cluster I. Combined with the analysis of
      the reported data, the Zhuang ethnic group shows remote affinity to those from
      North China, whereas it is close to those in South China. The frequencies of the
      radiation groups in Zhuangs, together with the phylogenetic relationship of the
      Zhuang ethnic group in the tree suggest that the Zhuang is a typical south
      population.

PMID- 11233266
TI  - [Composition of erythrocyte membrane lipids and their biophysical parameters in
      children with insulin-dependent diabetes during therapy].
AB  - Chronic secondary hyperglycemia in children with insulin insufficiency is
      characterized by quantitative and qualitative changes in membrane lipid spectrum
      and increased microviscosity of deep layers of peripheral blood erythrocyte
      membrane lipid bilayer. Traditional combined therapy does not normalize these
      parameters, which can lead to vascular complications in children with insulin
      dependent diabetes mellitus.

PMID- 11233267
TI  - [Evaluation of the glucose level in urine].

PMID- 11233268
TI  - [Analyzers for videodigital data recording in electrophoresis and immunoenzyme
      technique].

PMID- 11233269
TI  - [Analysis of specificity of immune complexes in HIV serotyping based on use of
      epitope-mimicking peptides (a literature review)].

PMID- 11233270
TI  - [Drug therapy and data from laboratory studies (a lecture)].

PMID- 11233271
TI  - [Atherosclerosis: polyenic fatty acids pathology (a literature review)].

PMID- 11233272
TI  - [Immunoenzyme technique for detection of natural antibodies to bradykinin in
      cardiovascular diseases].
AB  - A method for detecting natural antibodies to bradykinin by ELISA has been
      developed. A polymeric matrix model of peptide antigen has been synthesized for
      this purpose. Optimal conditions for detecting antigen and antibodies in the sera
      of donors and cardiovascular patients have been chosen. The level of antibodies
      to bradykinin is constant in donors and shifted in patients.

PMID- 11233273
TI  - [Specific antigenic preparations as inducers of blood leukocyte respiratory burst
      in chemiluminescent analysis].
AB  - Functional activity of blood leukocytes of normal subjects and patients with
      herpesvirus infection was studied by the chemiluminescent method in vitro with
      specific antigenic preparations (tick-borne encephalitis vaccine, ADPT vaccine,
      and herpetic vaccine). Functional response of blood leukocytes to vaccine
      preparations is specific and depends on the antigen and metabolic status of cells
      of recipients. The range of chemiluminescent response of blood leukocytes is
      wide: no changes in tick-borne encephalitis vaccine, weak response to herpetic
      vaccine, and pronounced changes in functional activity in response to ADPT
      vaccine. Testing with different doses of specific inducers helps additionally
      evaluate the metabolic reserve of blood leukocytes. A pronounced response of
      leukocytes to specific antigenic preparations in vitro (e.g. to ADPT vaccine)
      prompts development of methods for predicting the reaction of nonspecific
      reactivity system to vaccination.

PMID- 11233274
TI  - [Polystyrene latexes in agglutination tests: preparation and sensibilization].
AB  - A method for preparing polystyrene latexes for slide agglutination test is
      described. The latexes were used for preparing latex slide tests for evaluating C
      reactive protein and myoglobin. Effects of such factors as pH, temperature,
      antibody concentration, and latex particles concentration, on sensitization and
      agglutination have been studied. The proposed approaches allow detection of the
      antigen in a concentration of less than 200 micrograms/liter for myoglobin and
      less than 8 mg/liter for C-reactive protein.

PMID- 11233275
TI  - [Metaplasia and dysplasia of the bronchial epithelium (a literature review and
      modern concepts)].

PMID- 11233276
TI  - [Histochemical evaluation of phosphomonoesterase activity in the placenta in
      complicated pregnancy].
AB  - The levels of phosphomonoesterases (acid and alkaline) in chorions of born
      placenta, measured by the histochemical method, reflect various phases of the
      pathological process in gestosis. Adaptive changes in the structure and function,
      paralleled by increased phosphomonoesterase activities, are replaced by
      decompensation, formation of destructive and necrobiotic processes, combined with
      suppressed phosphomonoesterase activities in stubborn severe complications of
      pregnancy.

PMID- 11233277
TI  - [Diagnostic value of evaluation of desquamated endothelial cells in blood].
AB  - Circulating endotheliocytes as indicator of endothelial dysfunction were
      evaluated in the blood by Hladovec's method (1978) in patients with coronary
      disease, coronary stroke, insulin-dependent diabetes mellitus, and gestosis. The
      content of circulating (desquamated) endotheliocytes was increased in all
      patients, which reflected endothelial damage. The most pronounced changes were
      detected in patients with gestosis. Endotheliocyte content correlated with the
      concentration of Willebrandt's factor in the blood, which recommends using
      endotheliocyte count as a marker of endothelial damage.

PMID- 11233278
TI  - [Serodiagnosis in salmonelloses].
AB  - A method for preparing antigenic hydrosol diagnostic agent for hydrosol
      agglutination test is suggested. Efficiencies of hydrosol agglutination and
      passive hemagglutination tests in detection of antibodies to salmonella are
      compared. Arbitrary diagnostic titers are determined, diagnostic value of
      hydrosol agglutination test is assessed, time course of accumulation of specific
      antibodies is traced, and optimal terms of serological diagnosis of salmonellosis
      in patients of different age are determined.

PMID- 11233279
TI  - [Comparative evaluation of tree commercial diagnostic kits for detection of M.
      tuberculosis by polymerase chain reaction].
AB  - Three Russian commercial PCR diagnostic kits for detection of M. tuberculosis in
      clinical samples are compared. The kits were evaluated by sensitivity and
      convenience of analysis. The specificity and sensitivity of Russian diagnostic
      kits are not inferior to foreign analogs, but are not devoid of some drawbacks.

PMID- 11233280
TI  - [Analysis of genetic variability of strains of tick-borne encephalitis virus by
      primary structure of a fragment of the membrane protein E gene].
AB  - Primary structures of gene fragments of E protein (160 n.b.) have been determined
      for 29 tick-borne encephalitis (TBE) strains isolated from different parts of a
      territory. Analysis of homology of nucleotide sequences of these strains and data
      on 6 TBE strains published by other authors showed that they can be divided into
      6 groups (genotypes) by the following gene typing criteria: strain structure
      within the genotypes differing by no more than 9%, differences between strains of
      different genotypes are at least 12%. Based on these criteria, the prototype
      strains of the Far Eastern antigenic variant (Sofyin), Central European antigenic
      variant (Neudoerfle), and Vergina strain form different genotypes 1, 2, and 6,
      respectively. East Siberian strain Aina and Ural Siberian strain Lesopark-II
      belong to the same TBE virus genotype 3; two-thirds of analyzed strains belong to
      this genotype. Genotype 4 is represented by one strain 178-79, and genotype 5 by
      strain 886-84, both isolated in East Siberia.

PMID- 11233281
TI  - [Genetic typing of tick-borne encephalitis virus based on an analysis of the
      levels of homology of a membrane protein gene fragment].
AB  - All heretofore known genomic structures of tick-borne encephalitis (TBE) virus
      are analyzed. The authors prove the adequacy of using short fragment of E protein
      gene for characterization of philogenetic relationships between TBE strains.
      Three main genotypes of the virus are distinguished, one corresponding to Far
      Eastern variant, one to West, and the third includes strains belonging to Ural
      Siberian and Central Siberian and Transbaikal variants. Results of genetic typing
      by nucleotide sequences are confirmed by analysis of amino acid sequences of E
      protein fragments, specific marker amino acids in definite positions being
      determined for each genotype.

PMID- 11233282
TI  - [Protective activity of a bacterial plasmid, bearing the gene for the tick-borne
      encephalitis virus NS1 nonstructural protein].
AB  - Three intramuscular injections (50 micrograms each) with bacterial plasmid pMV45
      carrying nonstructural gene of NS1 protein of tick-borne encephalitis (TBE) virus
      protected 88% Balb/c mice from lethal challenge with the virus. Antibodies to NS1
      nonstructural protein were detected in the sera of vaccinated mice after the
      challenge. Absence of antibodies to E structural protein indicated absence of
      manifest infectious process in mice vaccinated with plasmid and challenged with a
      lethal dose of TBE virus.

PMID- 11233283
TI  - [Comparative in vitro study of the effectiveness of various immunomodulating
      substances in tick-borne encephalitis].
AB  - Suppressing effect of tick-borne encephalitis (TBE) virus on expression of
      lymphocyte subpopulation receptors has been demonstrated in vitro. Effects of 14
      immunomodulators on expression of T lymphocyte receptors under the effect of TBE
      virus have been compared. Anti-TBE immunoglobulin, 4-iodantipyrin, and
      leukinferon had the highest protective effect after a preventive injection.
      Thymalin and leukinferon in combination with human leukocytic interferon were the
      most effective within the treatment protocols. Further studies of sensitivity of
      immunoregulator cells to immunomodulators is recommended with the aim of adding
      these drugs to therapy of TBE patients.

PMID- 11233284
TI  - [Properties of influenza A and B, isolated from chick embryos and in MDCK cell
      culture].
AB  - MDCK culture was used along with the traditional chicken embryonated eggs (CEE)
      for improving the efficiency of isolation of epidemic influenza A and B viruses
      from clinical material. The number of influenza viruses isolated in both systems
      in epidemic seasons of 1997-1998 and 1998-1999 was as follows: 1 in MDCK and 21
      in CEE for influenza A(H1N1), 56 and 7, respectively, for influenza A(H3N2), and
      4 and 2 strains, respectively, for influenza B viruses. Influenza A viruses were
      heterogeneous by sensitivity to various erythrocytes, thermal stability of
      hemagglutinins, and transfer to another culturing system. Unlike the strains
      isolated in CEE, cultural viruses possessed a thermolabile hemagglutinin and more
      actively reacted with human and guinea pig erythrocytes. Evolution of influenza
      A(H3N2) viruses which is due mainly to changes in the hemagglutinin structure
      seems to be directed towards greater tropism to mammalian but not avian cells.
      Influenza B viruses are more homogeneous by antigenic and biological properties.

PMID- 11233285
TI  - [Detection of antiviral activity of monoclonal antibodies, specific to Marburg
      virus proteins].
AB  - Monoclonal antibodies (MAbs) specific to Marburg virus (MBG), Popp strain, have
      been previously produced and characterized by indirect ELISA. Protein specificity
      of MAbs was determined by immunoblotting with SDS-PAGE proteins of MBG: one to
      NP, four to VP40, and protein specificity of one antibody was not detected. The
      effect of MAb binding to protein epitopes on viral functions was investigated in
      vitro and in vivo. None of antibodies neutralized the virus in the neutralization
      test in vitro, but MAb 5G9.G11 and 5G8.H5 specific to MBG VP40 protein were
      active in antibody-dependent complement mediated lysis of virus-infected cells.
      In vivo these antibodies (5G9.G11 and 5G8.H5) protected guinea pigs from lethal
      MBG infection after passive inoculation. Studies of biological activity and
      analysis of epitope specificity of MAb-antiVP40 by competitive ELISA showed that
      2 of 7 epitopes of VP40 protein of MBG induce the production of protective
      antibodies. Hence, MAbs 5G9.G11 and 5G8.H5 reacting with MBG VP40 protein caused
      lysis of virus infected cells in the presence of the complement in vitro and
      protected guinea pigs from MBG infection by passive inoculation.

PMID- 11233286
TI  - [Virus-like particles as a source for obtaining antigens for diagnosing rubella].
AB  - Rubella diagnostic agents for hemagglutination inhibition (HI) and enzyme
      immunoassay (EIA) based on rubella virus-like particles (RVLP) have been
      developed. Noninfectious RVLPs containing three structural E1, E2, and C proteins
      were expressed in transfected CHO24S cell culture. HI titer in culture medium was
      1:256. Tween-80 treatment and ether increased HI titer 4-6-fold and rendered the
      antigen higher stability. Immunogenic properties of RVLPs were similar to the
      native rubella virus in HI test with international reference human rubella serum
      and sera from convalescents after rubella. Serum of mice immunized with RVLP
      reacted similarly with RVLP antigens and native virus. Antigen for EIA from RVLP
      was prepared by concentrating RVLP from culture fluid and partial purification by
      ultracentrifugation. The results of human sera testing by HI and EIA with RVLP
      and native virus antigens coincided. RVLP are identical to antigenic structure of
      the virus, are stable and easily purified, and can therefore be used for
      commercial production of HI and EIA antigens.

PMID- 11233288
TI  - [Development of delayed-type hypersensitivity to hog cholera].
AB  - Leukocyte migration inhibition test showed that pigs with classical swine fever
      develop delayed type hypersensitivity. The highest migration inhibition (65-85%)
      was observed in animals with the acute form, on day 3 after infection, or
      directly before death, or in animals immunized with reactogenic strain with
      clinical signs of disease. In some pigs with acute form the migrating capacity of
      leukocytes was restored on days 7-8 postinfection. Leukocyte migration inhibition
      factor is detected in the sera of pigs starting from day 3 after infection with
      the virulent strain. The degree of delayed type hypersensitivity correlated with
      the outcome of classical swine fever.

PMID- 11233287
TI  - [Transgenic plants in vaccinology].
AB  - The problem of transgenic plants application to production of antigens,
      antibodies, enzymes, and hormones is discussed. Transgenic plants are a highly
      effective system for production of bioactive molecules. Prospects for using
      transgenic plants expressing viral and bacterial antigens for mucosal
      immunization are discussed.

PMID- 11233289
TI  - [Optimization of a method for purifying antibodies for immunofluorescent
      diagnosis of influenza].
AB  - Efficiency and diagnostic adequacy of immunoglobulin isolation from rabbit immune
      serum by reiterated salting out with ammonium sulfate and subsequent separation
      of DEAE sephadex A-50 was evaluated. Electrophoresis and immunoelectrophoresis in
      agar gel demonstrated that the resultant immunoglobulin fraction is much more
      pure than after one salting out. It contains nothing more than antibodies to
      influenza virus taken for immunization, and after binding to the stain shows high
      fluorescent activity and induces but a moderate background nonspecific
      fluorescence in the subsequent preparations. In clinical trials of conjugates
      based on the new combined method of purification, influenza A or B could be
      correctly diagnosed in 97-98% cases.

PMID- 11233290
TI  - [Genetic analysis of West Nile fever virus, isolated in the south of the Russian
      plain (Volgograd and Astrakhan regions) in 1999].
AB  - Two strains of West Nile virus, Vlg 27889 and Ast 986, were isolated from the
      brain of a dead man and from the blood of a patient, respectively, during an
      outbreak of serous meningitis and meningoencephalitis in July-September, 1999, in
      the Volgograd and Astrakhan regions. Analysis of parts of genome of the strains
      cloned from cell culture by reverse transcription and polymerase chain reaction
      demonstrated their identity and appurtenance to group I West Nile viruses.

PMID- 11233291
TI  - [Mechanisms of morphine-induced rewarding effect: involvement of NMDA receptor
      subunits].
AB  - The glutamate receptor contributes to excitatory synaptic transmission in the
      central nervous system and plays an important role in memory acquisition,
      learning and neurological disorders. Molecular cloning studies have revealed that
      NMDA receptors consist of two families, the NR1 and NR2A-NR2D subunits, and NMDA
      receptors are thought to be pentameric or tetrameric complexes of the NR1 subunit
      with one or more of the NR2 subunits. It has been proposed that NMDA receptors
      are implicated in the development of opioid dependence. The non-selective NMDA
      receptor antagonist dizocilpine has been shown to suppress not only physical but
      also psychological dependence produced by morphine. An intracerebroventricular
      (i.c.v.) treatment with a specific antibody against the carboxyl-terminal region
      of the NR2B subunit abolishes the morphine-induced place preference, whereas
      antibodies against the NR1 and NR2A subunits do not affect the rewarding effect
      of morphine, indicating that the blockade of the NR2B subunit suppresses the
      development of the morphine-induced rewarding effect. Under these conditions, the
      NR2B subunit protein is up-regulated in the limbic forebrain of morphine
      conditioned mice. These findings suggest that the NMDA receptor, especially NR2B
      subunit, is an important modulator of the development and/or expression of
      psychological dependence on morphine.

PMID- 11233292
TI  - [The mechanisms of morphine dependence and it's withdrawal syndrome: study in
      mutant mice].
AB  - To investigate the involvement of catecholamines and/or the cyclic AMP (cAMP)
      systems in the development of drug dependence, we examined whether morphine
      dependence was developed in tyrosine hydroxylase (TH) heterozygous (TH+/-) and
      cAMP response element binding protein (CREB) binding protein (CBP) heterozygous
      (CBP+/-) mice. Morphine (10 mg/kg) induced place preference in the wild-type
      mice. In the TH+/- and CBP+/- mice, however, we could not find any morphine
      induced place preference. When the wild-type mice pretreated with morphine (10
      mg/kg) twice a day for 5 days were challenged with naloxone (5 mg/kg), they
      showed increased numbers of jumping, rearing and forepaw tremor as a sign of
      withdrawal symptom and increased level of cAMP in the thalamus/hypothalamus, but
      not in the striatum. However, increased numbers of jumping and forepaw tremor in
      the TH+/- and CBP+/- mice and increased level of cAMP in the
      thalamus/hypothalamus of TH+/- mice were not observed. These results suggest that
      catecholamines and CBP are involved in the development of morphine dependence,
      and that some changes in the catecholaminergic and/or cAMP system induced by
      repeated morphine treatment play an important role in the addiction of morphine.

PMID- 11233293
TI  - [Recent advances in research on nicotine dependence and reward mechanism].
AB  - Tobacco/nicotine dependence involves both psychological and physiologic
      dependence on nicotine. A recent summary of the clinical aspects of nicotine
      dependence disorders is provided in the ICD-10 of the WHO. There is growing
      evidence suggesting that nicotine depends on dopamine (DA) for its reinforcing
      effects. Suppression of DA function using DA-receptor antagonist affects the
      intravenous self-administration of nicotine, the discriminative properties of
      nicotine, nicotine-induced intracranial self-stimulation and nicotine-conditioned
      place preference. The increase inextracellular DA in the nucleus accumbens (NAcc)
      is a major factor that mediates the self-administration of nicotine. Recently,
      alpha 7-nicotinic receptors in the ventral tegmental area (VTA) contribute to the
      acute effects of nicotine on the mesolymbic DA system, reinforcing effects of
      nicotine and withdrawal symptoms from nicotine. The action of glutamate (Glu) at
      N-methyl-D-aspartate (NMDA)-sensitive receptors within the VTA is required for
      nicotine to stimulate DA release in the NAcc. Molecular epidemiological studies
      have shown that smoking behavior is more strongly influenced by a combination of
      the serotonin transporter gene and the neuroticism than by either factor alone.
      Clinically, bupropion, an antidepressant, has been licensed for use in USA to
      help patients stop smoking. The underlying mechanism is thought to be mediated by
      increasing the concentration of DA in the NAcc.

PMID- 11233294
TI  - [Characteristics of abnormal behavior induced by delta 9-tetrahydrocannabinol in
      rats].
AB  - delta 9-Tetrahydrocannabinol (THC), one of the active compounds of marihuana, is
      known to induce drug dependence and tolerance, and its action is weaker than
      those of other abused drugs in humans and animals. Acute effects of THC, "high",
      "irritable" and "cognitive deficits" are more important than the drug dependence
      and tolerance. For this reason, we examined characteristics of abnormal behavior
      such as catalepsy-like immobilization, aggressive behavior including irritable
      aggression and muricide, and spatial cognition impairment induced by acute and
      chronic treatments of THC in rats. The catalepsy-like immobilization is related
      to a decrease in catecholaminergic and serotonergic neurons in the nucleus
      accumbens and amygdaloid nucleus and thus serves as a useful model for
      amotivational syndrome, one of cannabis psychoses. In aggressive behavior,
      muricide was determined by the housing condition. Muricide was induced if the rat
      was placed under an isolated housing condition within the period of the effect of
      single injection of THC. The behavioral change resembles exacerbation and
      flashback in humans. Spatial cognition is impaired by the interaction between
      cannabinoid (CB1) and 5-HT2 receptor in the dorsal raphe-hippocampal serotonergic
      neurons. Thus the abnormal behavior induced by THC can be a useful model for
      investigating mental function in humans and new drugs for the treatment of mental
      disorders.

PMID- 11233295
TI  - [Amotivational syndrome in organic solvent abusers].
AB  - Amotivational syndrome is a chronic psychiatric disorder characterized by a
      variety of changes in personality, emotions and cognitive functions such as lack
      of activity, inward-turning, avolition, apathy, incoherence, blunted affect,
      inability to concentrate and memory disturbance. The syndrome was first described
      among those patients with a history of longtime cannabis use in the 1960's. Since
      then, there have been several reports describing similar psychiatric disorders to
      amotivational syndrome among patients with the history of some other psychoactive
      substances use including solvents, methamphetamine and OTC cough syrups.
      Therefore, the syndrome has been recognized as one of the common psychiatric
      conditions that might develop in patients with a history of any psychoactive
      substance use. Recently, more attention has been paid to the biological basis of
      amotivational syndrome. Several studies using MRI, SPECT or neuropsychological
      measures have revealed white matter changes, hypoperfusion in the frontal cortex
      of the brain and impairment of frontal lobe function. Those findings suggest that
      amotivational syndrome might be related to "hypofrontality" of the brain.
      Although no specific treatments have been reported to be definitely effective for
      patients with amotivational syndrome, some neuroleptics with activating
      properties or antidepressants can be given appropriately to treat the chief
      symptoms of the patients.

PMID- 11233296
TI  - [Animal models of drug dependence using the drug self-administration method].
AB  - This paper will review 1) experimental models of drug-seeking behavior and 2)
      mechanisms underlying the behavior, focusing on cocaine self-administration.
      After the acquisition of self-administration, vigorous lever-pressing is
      generally observable after the drug was replaced by saline. This lever-pressing
      behavior under saline infusion can be considered "drug-seeking behavior". Drug
      seeking behavior is reinstated by non-contingent injection of the drug, stress
      exposure and presentation of drug-associated stimuli even after extinction. This
      is called a relapse/reinstatement model. Electrophysiological studies showed that
      the majority of accumbal neurons is tonically inhibited during cocaine self
      administration and exhibited phasic increases in firing time-locked to cocaine
      self-infusion, which might represent the craving state or drive animals to drug
      seeking behavior. Voltammetry and microdialysis studies indicated that the timing
      of drug-seeking responses can be predicted from fluctuations in accumbal
      extracellular dopamine concentration. Whereas dopamine D2-like agonists
      reinstated extinguished cocaine-seeking behavior, D1-like agonists prevented the
      relapse in cocaine-seeking behavior induced by cocaine itself. Given that an AMPA
      receptor antagonist, but not dopamine antagonist, prevented cocaine-seeking
      behavior induced by cocaine, glutamate transmission in the nucleus accumbens is
      thought to be important for expression of craving or drug-seeking behavior.

PMID- 11233297
TI  - [Advanced findings on the molecular mechanisms for behavioral sensitization to
      psychostimulants].
AB  - Repeated administration of psychostimulants like methamphetamine and cocaine
      induce behavioral sensitization, which is recognized as an animal model for
      dependence and psychoses. Many previous studies have proved two major cascades
      play a crucial roles for molecular mechanisms underling sensitization. The first
      one is activation of D1 dopamine receptors by robust increase of dopamine
      release, followed by activation of adenylyl cyclase, increase of cyclic AMP,
      activation of protein kinase A (PKA) and phosphorylation of proteins by PKA. The
      second one is activation of NMDA receptor by enhanced release of glutamine,
      followed by increased intracellular Ca2+ concentration, formation of
      Ca2+/calmodulin complex, and phosphorylation of several proteins such as
      calcineurin, CaM-K II and nitric oxide synthase. Recent advanced findings on
      sensitization mechanisms were reviewed from three different aspects: 1) Studies
      using knockout mice offered quite amazing findings that D1DA-receptor-lacking
      mice or dopamine-transporter-lacking mice can develop sensitization and
      dependence, which were not consistent with the previously established hypotheses
      based on behavioral pharmacology. In addition, those data showed the important
      roles of vesicular monoamine transporter 2, 5HT1B receptors and delta FosB. 2)
      Research on neural-plasticity-related sensitization revealed the involvement of
      several molecules such as tissue plasminogen activator, arc (activity-regulated,
      cytoskeleton-associated), synaptophysin and stathmin. Increased expression of
      these genes may participate in the rearrangement of neural networks with
      synaptogenesis and expansion of dendrites 3) Trials to discover novel-genes
      involved sensitization phenomenon using differential display or subtraction
      cloning found some candidate genes, mrt-1, NAC-1 and CART. Although in these
      areas are still in progress, accumulating findings will elucidate the details of
      the molecular mechanism of behavioral sensitization and dependence.

PMID- 11233298
TI  - [Pharmacological study and clinical effect of HIV protease inhibitor amprenavir].
AB  - Amprenavir is a novel protease inhibitor with antiviral activity, and was
      approved in the U.S. (AGEN-ERASE) in 1999 for use in combination with other
      antiretrovirals for the treatment of HIV infection. The drug is developed by
      Kissei Pharmaceuticals Co., Ltd. in Japan, approved in the same year, and has
      been distributed by them (PROZEI). Amprenavir achieves a viral load of less than
      400 copies/ml when it is given in triple combination therapy in both therapy
      naive patients and patients previously treated with nucleoside reverse
      transcriptase inhibitors (NRTI). The recommended dose of amprenavir is eight 150
      mg capsules, twice daily, or 1200 mg, b.i.d. Amprenavir may be taken with or
      without a meal; however, it should not to be taken with high-fat meals because
      its oral bioavailability may possibly be affected by fat. One of the major
      concerns associated with anti-HIV agents is the resistance mutation development,
      and the presence of I50V, M46I/L, I47V, I54L/V and I84V genotype has been
      observed in amprenavir therapy experienced subjects. Differences in resistance
      patterns and resistance mutation interactions may have amprenavir recognized as
      an alternative choice of drugs in maintaining efficacy. Therefore, amprenavir is
      believed to add an important treatment option in HIV infection therapy. It should
      be noted that P450 isozyme CYP3A4 is responsible for amprenavir; thus, care must
      be taken to avoid combined amprenavir with drugs that affect the action of
      CYP3A4, that act on the production CYP3A4 substrates, or that are metabolized by
      CYP3A4 metabolism. Amprenavir is the fifth protease inhibitor approved in Japan,
      and it is important to understand its differential and identical properties from
      other protease inhibitors to maximize its efficacy.

PMID- 11233299
TI  - [Atorvastatin (Lipitor): a review of its pharmacological and clinical profile].
AB  - Hypercholesterolemia is a major risk factor for the development of coronary heart
      disease. HMG-CoA reductase inhibitors have been used as first-line drugs because
      of both their superior cholesterol lowering effect and reliable safety profile.
      Since there are many patients whose plasma cholesterol level does not reach the
      therapeutic target even if reductase inhibitors are available, more effective
      drugs have been strongly required for a long time. Atorvastatin, one of the most
      recently introduced statins, produces greater plasma LDL-cholesterol reductions
      than other statins. This pronounced effect of atorvastatin seems to be due to its
      long-lasting action, presumably a reflection of longer residence time of
      atorvastatin and its active metabolites in the liver. Clinical trials of
      atorvastatin have also demonstrated marked plasma triglyceride reductions. The
      triglyceride reduction with atorvastatin seems to stem from the following two
      indirect mechanisms, limiting VLDL secretion from the liver and increase in
      clearance of triglyceride-rich lipoprotein via induced LDL receptors from plasma.
      Eleven clinical trials of atorvastatin, which have been developed in Japan,
      clearly demonstrated its ability to reduce LDL-C levels more strongly and in
      significantly more patients to LDL-C treatment goals than other reductase
      inhibitors with similar safety profiles. Therefore, atorvastatin adds a new
      dimension to the effective management of hypercholesterolemia and combined
      hyperlipidemia.

PMID- 11233300
TI  - [Effects of bofu-tsusho-san, a traditional Chinese medicine, on body fat
      accumulation in fructose-loaded rats].
AB  - The effects of Bofu-tsusho-san (BOF), a traditional Chinese medicine, on fructose
      induced hypertriglyceridemia and body fat accumulation were investigated in
      female SD rats. Rats were allowed to drink ad libitum 25% (w/w) fructose solution
      for 6 weeks. BOF was administered to the rats as an experimental diet containing
      1.5% or 4.5% (w/w) of BOF during the fructose-loading period. BOF suppressed body
      weight gain and prevented the elevation of serum triglyceride levels and body fat
      accumulation in fructose-loaded rats without affecting food and fructose intake.
      Furthermore, BOF prevented the increase of triglyceride content in the liver and
      the reduction of mitochondrial cytochome c oxidase activity in the brown adipose
      tissue induced by fructose. From these results, it has been suggested that BOF
      has a preventive effect against the body fat accumulation caused by excess intake
      of sugar or other fructose-containing foods. The inhibition of triglyceride
      synthesis in the liver, and the enhancement of lipolysis in adipocytes and of
      thermogenesis in brown adipose tissue have been presumed as the mechanisms of
      action of BOF.

PMID- 11233301
TI  - [Parkinsonism induced by MPTP and free radical generation].
AB  - Oxygen free radical formation has been implicated in dopaminergic toxicity caused
      by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and iron. Although MPTP
      produces a parkinsonian syndrome after its conversion to 1-methyl-4
      phenylpyridine (MPP+) by type B monoamine oxidase (MAO-B) in the brain, the
      etiology of this disease remains obscure. MPP+ is one of the most potent dopamine
      (DA)-releasing agents. Iron-catalyzed DA autoxidation and oxidative stress may be
      involved in the pathogenesis of Parkinson's disease. If indeed the effect of MPP+
      on hydroxyl radical (.OH) formation is due to DA release, reserpine-induced DA
      depletion may reduce MPP(+)-induced .OH formation. Imidapril, an angiotensin
      converting enzyme (ACE) inhibitor, can resist MPP(+)-induced .OH formation via
      suppression of release of DA by angiotensin. Histidine, a singlet oxygen (1O2)
      scavenger, protects MPP(+)-induced .OH formation. Fluvastatin, an inhibitor of
      low-density lipoprotein (LDL) oxidation, can resist MPP(+)-induced .OH formation.
      The inhibitory effect on the susceptibility of LDL oxidation can reduce .OH
      generation. These drugs may be applied as antiparkinsonian agents. Further
      clinical investigation is necessary in the future.

PMID- 11233302
TI  - [Pharmacological treatments of Parkinson's disease].
AB  - Antiparkinsonian agents applied or under the investigation for the treatment of
      patients with Parkinson's disease were reviewed. Tremor, akinesia, rigidity and
      postual instability are key signs of Parkinson's disease. The most important one
      is akinesia, which includes decreased spontaneous locomotor activity, slowness of
      movement, awkwardness and freezing. The main pathophysiology of Parkinson's
      disease is neurodegeneration of nigrostriatal dopaminergic neurons. Neurotoxins
      or oxidative stress to the dopaminergic neurons have been discussed as one of the
      etiologies of degeneration. Antioxidant or neuroprotective agents will be the
      future drugs for Parkinson's disease. At present, supplement of dopamine by
      levodopa administration, retarding the metabolism of levodopa or dopamine by a
      dopa decarboxylase inhibitor (DCI), MAO-B (monoamine oxidase inhibitor type B)
      inhibitor or catechol-O-methyltransferase (COMT) inhibitor, dopamine receptor
      agonists, anticholinergic agents, dopamine release enhancer/uptake inhibitor, N
      methyl-D-aspartate (NMDA) receptor antagonists are applied for the treatment of
      Parkinson's disease. New agents such as adenosine receptor antagonists,
      serotonergic agents and nicotinic receptor agonists are under investigation.
      Agents to facilitate the growth of nerves or to inhibit degeneration of nerves
      are also studied and will be developed for the treatment of Parkinson's disease
      in the future. In the case of familial Parkinson's disease, abnormal genes were
      identified. Gene therapy might be another future treatment for these cases.

PMID- 11233303
TI  - [Pharmacological and clinical properties of beraprost sodium, orally active
      prostacyclin analogue].
AB  - Prostacyclin is an endogeneous eicosanoid synthesized by vascular endothelial
      cells, and has potent inhibitory effects on platelet adhesion/aggregation and
      vasoconstriction. However, its therapeutic use is restricted by its extremely
      short half-life. Beraprost sodium (beraprost) is the first orally active
      prostacyclin analogue developed by TORAY Industries, Inc. Beraprost possesses a
      phenol moiety instead of the exo-enol ether moiety, which is the cause of the
      instability of prostacyclin, and has a modified omega-side chain that contributes
      to dissociating antiplatelet action from adverse reactions. In 1992, beraprost
      was approved as a drug for chronic arterial occlusion. Beraprost is now widely
      used clinically as "Dorner" or "Procylin". The indication for "primary pulmonary
      hypertension" was also approved in 1999. Recently in Europe, a placebo controlled
      trial named "Beraprost et Claudication Intermittent-2 (BERCI-2)" was performed,
      and it was reported that beraprost improved the walking distances of the
      patients. Beraprost has a variety of biological activities such as antiplatelet
      effects, vasodilation effects, antiproliferative effects on vascular smooth
      muscle cells, cytoprotective effects on endothelial cells and inhibitory effects
      on the production of inflammatory cytokines. On the basis of basic and clinical
      research, it has been suggested that beraprost is also effective for many
      intractable diseases. We expect that the relationship between reduced
      prostacyclin level and these diseases would be clarified and the beneficial
      effects of beraprost would be demonstrated by controlled clinical trials in the
      future.

PMID- 11233304
TI  - [Pharmacological profiles of mycophenolate mofetil (CellCept), a new
      immunosuppressive agent].
AB  - Mycophenolate mofetil (MMF, CellCept), a semisynthetic derivative of mycophenolic
      acid (MPA) produced by a fungus, is an inhibitor of the inosine monophosphate
      dehydrogenase (IMPDH) enzyme (IC50 = 25 nM) that catalyzes the synthesis of
      guanosine monophosphate (GMP) from inosine. GMP is an essential nucleoside for
      purine synthesis during cell division. As T and B-lymphocytes almost exclusively
      use the de novo pathway of purine synthesis, these cells are particularly
      sensitive to the inhibitory action of MMF. It has a mechanism of action distinct
      from cyclosporine and tacrolimus. Although MMF does not affect cytokine
      production, by inhibiting the rate-limiting enzyme IMPDH in the de novo synthesis
      of purines, it inhibits the proliferation of T and B-lymphocytes, the production
      of antibodies, and the generation of cytotoxic T lymphocytes. Reversal of acute
      allograft rejection and increased survival of kidney, heart and bone marrow cell
      allograft has been shown in several animal studies. Moreover, it was suggested
      that MMF combined with CsA prevented the acute rejection, and approximately half
      of the animals became long-term survivors. The Ministry of Health and Welfare
      approved MMF in 1999 for use for rejection treatment in renal transplantation
      based on several prospective, randomized and blind efficacy trials.

PMID- 11233306
TI  - Inside JCAHO surveys: a guide to help CE departments prepare.

PMID- 11233305
TI  - [Gastrointestinal sparing anti-inflammatory drugs--COX-2 selective inhibitors and
      NO-releasing NSAIDs].
AB  - The use of NSAIDs is associated with a wide array of alterations in the
      gastrointestinal integrity and function. Various approaches have been taken to
      develop NSAIDs with reduced gastrointestinal toxicity, and few have successfully
      reduced the incidence of adverse reactions. These include COX-2 selective
      inhibitors and NO-releasing NSAIDs. Much has been written about the potential of
      COX-2 inhibitors as antiinflammatory agents that lack the gastrointestinal side
      effects of traditional NSAIDs. COX-2 expression is most evident at sites of
      inflammation, while COX-1 accounts for most of the PG synthesis in the normal
      gastrointestinal tract. However, there are distinct examples of circumstances in
      which COX-2-derived PGs play a role in the maintenance of the mucosal integrity,
      and the differentiation of COX-1 and COX-2 is not quite as clear as has been
      suggested. On the other hand, the rational behind the NO-releasing NSAIDs is that
      NO released from the derivatives exerts beneficial effects on the
      gastrointestinal mucosa. The present article overviews the roles of COX and NO in
      housekeeping functions of the gastrointestinal mucosa in various circumstances
      and the effects of gastrointestinal sparing NSAIDs, such as COX-2 selective
      inhibitors and NO-releasing NSAIDs, on the ulcerogenic and healing responses in
      the gastrointestinal mucosa.

PMID- 11233307
TI  - Development of a charged-coupled device-based light-scattering instrument for the
      detection of C-reactive protein using particle-enhanced immunoassay.
AB  - A novel light-scattering instrument has been developed for rapid detection of
      immunoreactions in test latex particle-enhanced immunoassays. The detector
      consists of a flat-field grating and a charge-coupled device mounted on a
      rotating platform, and the detector measures a continuous spectrum from 350 nm to
      735 nm at 440 polar angles with a resolution of 0.5 degrees. Optimal detection
      for rates of immunoreaction were determined by intensity of scattered light at
      different angles. Instrumental precisions were all shown to fall within 5% of the
      target relative standard deviation limits. The accuracy of the instrument was
      confirmed using monodispersed latex particles of known size and shape. The
      initial results showed the possibility of a sensitive and accurate detection of C
      reactive protein throughout the range of clinical interest, thus demonstrating a
      significant potential for biomedical applications.

PMID- 11233308
TI  - The design and development of a biosensor to measure the concentration of
      meconium in amniotic fluid.
AB  - Meconium aspiration syndrome occurs in 0.2% to 1% of all deliveries and has a
      mortality rate as high as 18%. The disease is responsible for 2% of all perinatal
      deaths. Meconium may be classified as being thick or thin, but this assessment is
      normally performed visually by clinicians. A "meconiumcrit" analysis has been
      developed to objectively define the concentration of meconium. However, this
      analysis does not provide real-time continuous readings. This study focused on
      the design and development of a sensor to provide an objective, continuous, real
      time assessment of meconium thickness. Meconium has an absorption spectrum
      centered at 410 nm and observes Beer's law. Blue light centered at 430 nm was
      delivered through meconium solutions, and a photodiode translated the strength of
      the incoming light into a voltage. This voltage was analyzed by a microcontroller
      to determine the concentration of meconium.

PMID- 11233309
TI  - A computerized maintenance management system's requirements for standard
      operating procedures.
AB  - From this review of the 6 aspects of opportunity for inconsistency to corrupt or
      skew the reliability of data, it becomes apparent why members of management must
      provide the standards of operation and use within the CMMS for their employees.
      The possibility of poor data integrity due to any one of these aspects may not be
      severe; however, the severity is compounded and inevitable when different aspects
      are combined. Responding to information collected through the CMMS can be
      effective only if the data are reliable. With SOPs, management has provided their
      personnel with the necessary tools to ensure department-wide consistency.
      Management cannot afford to allow any one [table: see text] individual to apply
      personal interpretations of the importance and requirements in their approach to
      using the CMMS. If this is permitted, the loss of integrity due to one
      individual's judgment grows rapidly when data are analyzed at the departmental
      level. Standard operating procedures go beyond creating a "how to" for the CMMS;
      they provide the critical elements for collecting responsible and reliable data.

PMID- 11233310
TI  - Legal testimony: the dos and don'ts.

PMID- 11233311
TI  - Wireless local area network fundamentals: Part 2.

PMID- 11233312
TI  - [Thrombosis of the renal transplant vein].
AB  - In this study, three cases have been reported of renal transplant vein
      thrombosis, which is a rare complication associated with renal transplant. The
      positive diagnosis is frequently made at a later date, and is established by
      Doppler ultrasonography. The prognosis is poor. Only an early diagnosis and
      immediate surgical investigation can possibly save the transplant. To reduce the
      incidence of renal transplant vein thrombosis, donors should be carefully
      screened for potential risk factors; the transplant technique should be
      completely mastered; and postoperative anticoagulant treatment, including further
      studies in this regard, may help to prevent this complication in at-risk
      patients. At present, however, the graft generally has to be removed.

PMID- 11233313
TI  - [Extra-adrenal pheochromocytoma discovered peroperatively].
AB  - In this study, an uncommon case has been reported of an ectopic pheochromocytoma
      without the presence of any clinical symptoms. The radiological investigations
      showed a right retroperitoneal tumor without any kidney involvement. The
      diagnosis was established by biopsy and subsequent histological findings. In the
      course of surgery as the large tumor mass was being removed, tachycardia was
      observed which caused the resection to be performed as rapidly as possible. Once
      the tumor had been removed, bradycardia occurred, followed by cardiac arrest:
      although the latter was stabilized after cardiac massage, the patient died one
      hour after the operative field had been closed. In addition to this case report,
      the diagnosis, therapeutic strategy and prognosis regarding an ectopically
      located pheochromocytoma have been discussed.

PMID- 11233314
TI  - [Pheochromocytoma in Africa: rarity, gravity and ectopy].
AB  - Pheochromocytoma is one of the main curable etiologies of high blood pressure,
      although its diagnosis and therapeutic management can be problematical: an
      incorrect diagnosis or inappropriate treatment may lead to fatal complications.
      This disease was exceptionally uncommon in the 1950s, and 30 years later about 30
      cases had been reported; however, since 1981 there has been a progressive
      increase in the incidence of pheochromocytoma (48 documented cases in Africa). In
      Africa, this disease has two particular characteristics: the gravity of the
      clinical symptoms, mainly due to the physiological and pharmacological effects of
      catecholamines which as a result of this disease are stored and liberated at very
      high rates; and the ectopic site in a number of cases. To facilitate the
      diagnosis of pheochromocytoma improved clinical investigation is therefore
      advocated, but the necessary medical equipment is not always available in Africa.
      On this continent, the ectopic factor confirms the observations made in the early
      1980s, and should be taken into consideration in the diagnosis and management of
      this disease.

PMID- 11233315
TI  - [Phenotype B primitive adrenal lymphoma, diagnosed by percutaneous aspiration
      biopsy].
AB  - The authors report a case of primary adrenal lymphoma in a 30-year old-female who
      complained of lumbar pain and was in poor general condition. Ultrasonography and
      CT scan revealed a heterogeneous mass with necrosis in the left adrenal gland.
      Non-Hodgkin's lymphoma of B-cell origin was determined by ultrasound-guided
      aspiration biopsy of the adrenal mass. Taking this case and the findings in the
      literature into consideration, the features of this disease have been reviewed
      and the problem of diagnosis, treatment and prognosis have been examined.

PMID- 11233316
TI  - [Acute renal insufficiency due to hydronephrosis].
AB  - Acute renal failure due to hydronephrosis is a rare pathology. It can occur
      unilaterally, or as a pyelo-ureteral junction (PUJ) bilateral syndrome. In the
      present study, two cases have been reported. The diagnosis was based on
      ultrasonographic findings which showed hydronephrosis, and on descending pyelo
      ureterography (DPU), which demonstrated an absence of opacification. Infection
      was present in one case. Preliminary treatment consisted of percutaneous
      nephrostomy, followed by surgical pyelo-ureteral resection and Anderson-Hynes
      pyeloplasty which gave good results (95% success rate), and which enabled a
      satisfactory recovery of renal function to be obtained.

PMID- 11233318
TI  - [A new case of pseudotumoral renal tuberculosis].
AB  - The incidence of urogenital tuberculosis is still frequent and constitutes a
      current public health problem in Morocco, a country in which tuberculosis is
      endemic. The clinical presentation of this form of the disease may be misleading.
      The pseudotumoral type of renal tuberculosis is extremely uncommon, and in this
      study this disease has been described in a young patient. The radiological
      findings suggested the possibility of this lesion being renal cancer. The
      preliminary diagnosis was corrected and a definitive diagnosis of pseudotumor was
      made following pathological examination of the surgically-removed kidney.

PMID- 11233317
TI  - [Inflammatory pseudotumors of the kidney: a case report].
AB  - Inflammatory pseudotumors are uncommon benign tumors of unknown etiology which
      may develop at several anatomical sites, e.g., the airways and gastrointestinal
      tissues, soft tissues, the orbit, the spleen, or the lymph nodes. The renal site
      is extremely rare, and presents the problem of differential diagnosis as the
      clinical and radiological aspects of this tumor are similar to those of an
      adenoma or an angiomyolipoma, and suggest the presence of a carcinoma, in
      particular a cystic renal carcinoma which is also a rare form of tumor. There is
      therefore a risk that this benign lesion could be misdiagnosed. Due to the good
      prognosis associated with this type of tumor, in cases where the definitive
      diagnosis has been established no surgical procedure is necessary. However, the
      difficulty in making this diagnosis preoperatively means that in general the
      organ has to be surgically removed so that a histological analysis can be made
      and the negative or positive findings confirmed. In the present study, the case
      of an inflammatory pseudotumor of the kidney has been described. In this
      instance, radical nephrectomy of the left kidney was carried out as the disease
      was presumed to be renal cell adenocarcinoma. However, the histopathological
      analysis was negative as regards malignancy, and indicated the presence of an
      inflammatory pseudotumor. This article raises the question of the problem in
      establishing a preoperative definitive diagnosis, as a correct diagnosis is often
      only confirmed following nephrectomy (in cases where the contralateral kidney is
      healthy).

PMID- 11233319
TI  - [Aglomerular segmental hypoplasia of the kidney: report of a clinical case].
AB  - Aglomerular segmental hypoplasia of the kidney is a disease that is uncommon in
      the adult; the average age at appearance of symptoms is between ten and 15 years.
      A clear female predominance has been noted, and this disease is often
      misdiagnosed as chronic pyelonephritis. However, the radiological and
      pathological characteristics are different to the latter. The etiology of
      aglomerular segmental hypoplasia has not yet been determined. It is important to
      acquire further knowledge regarding this disease, as in certain cases this
      information could help to avoid unnecessary nephrectomy.

PMID- 11233320
TI  - [Emergence of terminal diabetic nephropathy in insulin-dependent diabetes in
      young Black Africans: report of five cases from Dakar].
AB  - The authors have reported five cases of end stage diabetic nephropathy. Thi
      growing disease has began to reduce vital prognosis of Black african insulin
      independent diabetic. So, economic and social problem for their resolution
      (hemodialysis, kidney graft) is going to appear.

PMID- 11233321
TI  - [Pyelocolic fistula: a case study].
AB  - In this study, the case has been reported of a left renocolic fistula that was
      detected in a patient with hepatitis C and cirrhotic complications who was
      hospitalized for urogenital tuberculosis. It was decided to perform left
      nephrectomy and digestive suture, but surgery was delayed due to hemostatic
      abnormalities and massive cytolysis, and the patient died before surgical
      treatment, three days after the discovery of the fistula. The findings in the
      literature have been reviewed, and the common occurrence of this type of fistula
      has been underlined. They are the most frequently encountered type with of entero
      urinary fistula, and account for 60% of documented cases. Their etiological and
      clinical characteristics of have been described in detail. In general, treatment
      consists of performing a nephrectomy and digestive suture.

PMID- 11233322
TI  - [Leiomyoma of the urinary tract].
AB  - Leiomyomas of the urinary tract are benign and uncommon forms of tumor. In the
      present study, two cases have been described of leiomyomas situated in the
      bladder. Following this description, the pathological characteristics and the
      diagnostic and therapeutic aspects of these lesions have been examined. The
      clinical symptomatology depends on the tumor site, and this type of lesion is
      more frequently found in women.. Treatment mainly consists of endoscopic
      resection, but may involve cystectomy. The prognosis for patients with this type
      of tumor is invariably favorable.

PMID- 11233323
TI  - [Laparoscopic nephrectomy in the liver donor: introduction of the method and
      preliminary results].
AB  - INTRODUCTION: The shortage of organs available for renal transplantation has
      focussed attention on the use of live donors. Techniques for laparoscopic
      nephrectomy have recently been described, which have limited morbidity, duration
      of hospitalization and the period off work. However, these surgical procedures
      are difficult, and may be risky for the organ to be transplanted. METHOD: The
      laparoscopic live donor nephrectomy was introduced in stages, including the use
      of a videoconference from a reference center. In this article, the prospective
      analysis of the present authors' preliminary results has been presented. RESULTS:
      Ten kidneys were removed by laparoscopy, i.e., three from the left and seven from
      the right side. No conversion of this technique to laparotomy was necessary. The
      mean warm ischemic time was five minutes, and in the last six operations it did
      not exceed three minutes. The patients were able to leave hospital between four
      and eight days following surgery. After a mean follow-up of 10.5 months, organ
      survival was 100%, and in all grafts excellent function was observed. CONCLUSION:
      The quality of these preliminary results which may act as a reference and the
      careful introduction of a live donor laparoscopic program could provide an
      incentive to potential donors, and thereby increase the pool of organs available
      for transplantation.

PMID- 11233324
TI  - [Retroperitoneal neuroblastoma in the adult: case report and review of the
      literature].
AB  - Retroperitoneal neuroblastoma is a rare embryonic tumor of the sympathetic
      nervous system that is specific to the child. In this study, the case is reported
      of an infant who underwent median laparotomy at the age of 14 months for a tumor
      which occupied the left half of the abdomen. The lesion was large, hard, and not
      very mobile. It was considered to be unresectable, and the histological findings
      after biopsy showed it to be a neuroblastoma. Radiotherapy was then initiated,
      which successfully reduced the tumor size. A second investigation at the age of
      three years detected an unresectable tumor of 5 cm. A further biopsy was
      performed, and the histological findings showed the lesion to be a partially
      developed ganglioneuroblastoma. The patient has been followed up regularly by
      ultrasonography which has shown no increase in tumor size. She is now 20 years
      old, and is asymptomatic. The last computed tomography scan visualized a 62-mm
      retroperitoneal mass with no metastases. Surgery was decided against in favor of
      regular monitoring. This case is particular due to the prolonged survival of the
      patient, regression of histological stage, and reduction in size of the tumor
      after radiotherapy. It is remarkable that the diagnosis of neuroblastoma was made
      when the patient was 14 months old, and that she is still alive at 20 years old.

PMID- 11233325
TI  - Leiomyosarcoma of the prostate: a study of two cases.
AB  - Leiomyosarcoma of the prostate is rare neoplasm that accounts for less than 0.1%
      of prostate malignancies. A number of treatment approaches have been adopted
      including radical surgery, radiotherapy and chemotherapy, but in no instance has
      a successful outcome been obtained. Prostate leiomyosarcoma has a poor prognosis,
      although survival time can vary. For these reasons, it is important to correctly
      identify this disease and report its occurrence, type of treatment, and the
      response to therapy of each patient diagnosed as having leiomyosarcoma of the
      prostate in an attempt to improve our understanding of the natural history of
      these lesions.

PMID- 11233326
TI  - [Prolapse of the urethral mucosa in young girls from the Ivory Coast].
AB  - In this retrospective study covering a nine-year period, 65 cases have been
      analyzed of prolapse of the urethral mucosa in young girls (aged between six
      weeks and 14 years) from the Ivory Coast. The aim of this study was to describe
      the etiology of this disorder, and to demonstrate the utility of ambulatory
      surgery. The main reason for the detection of this disorder was mild genital
      hemorrhage in 37 cases, which was related to rape in eight instances and to other
      types of trauma in nine cases, thereby raising serious medico-legal problems.
      Various forms of treatment were used (medical and/or surgical). The medical
      approach consisted of antibiotic and antiinflammatory treatment, combined with a
      local antiseptic. Two surgical approaches were adopted, either the Doria method
      in which the necrosed tissue is spontaneously eliminated after three to five
      days, or surgical excision under general anesthesia of the prolapsed mucosa
      followed by seromucosal stitching. The results were satisfactory in all cases,
      and in the surgically operated cases no complications or recurrence were noted at
      one-year follow-up.

PMID- 11233327
TI  - [Primitive seminoma of the mediastinum: a case report].
AB  - In this study, the case has been reported of a 36-year old male who was treated
      at the Ibn Rochd Oncology Center in Casablanca for a primary mediastinal seminoma
      revealed by a symptomatology including cough, dyspnea, laterocervical swelling,
      rachidial pain and gait disorder. The preliminary investigation showed
      significant mediastinal enlargement with a right pleuritis and vertebral
      metastases; tumor markers were normal. The diagnosis of seminoma was confirmed by
      pathological and immunohistochemical analysis of the cervical adenopathy. Disease
      management consisted of BEP/cisplatin type chemotherapy and lumbar, mediastinal,
      and supraclavicular radiotherapy. The response after four courses of combined
      chemo-/radiotherapy was estimated at 25%, but the patient died from respiratory
      failure five months after the initiation of treatment.

PMID- 11233328
TI  - [Giant scrotal condyloma acuminata: a case report].
AB  - In this study, the case has been reported of a scrotal tumor in a 50-year old
      male admitted with a large warty lesion at the base of the scrotum which
      resembled a giant condyloma accuminatum (Buschk-Lowenstein tumor). The HIV
      serology was negative, but the papillomavirus findings were positive. A complete
      resection of the tumor was performed. The histological findings confirmed the
      diagnosis of condyloma accuminatum without evidence of degenerative development
      into a squamous cell carcinoma. The clinical course was favorable, and no local
      recurrence was observed at 16 months follow-up. The problems that are frequently
      encountered in the diagnosis and therapy connected with this type of tumor have
      also been discussed.

PMID- 11233329
TI  - "A lifetime commitment to excellence in patient care through shared new
      knowledge".

PMID- 11233330
TI  - Clinical grading of the upper palpebral conjunctiva of non-contact lens wearers.
AB  - PURPOSE: To categorize the appearance of the normal upper palpebral conjunctiva
      using a grading scale and to investigate interobserver agreement with a grading
      scale modified to include decimal increments. METHODS: Upper palpebral
      conjunctival appearance of 96 non-contact lens wearing subjects aged 18 to 75
      years was assessed using a photographic grading scale that has a generic (zero to
      four) scale to score redness and roughness of the palpebral conjunctiva. RESULTS:
      Median redness and roughness was about 1.25 units. About 5% of subjects had
      redness or roughness >2.0 units. Interobserver agreement improved during the
      study. By the end of the study, the standard deviation of the discrepancy scores
      was 0.12 to 0.19 units. CONCLUSIONS: Upper palpebral conjunctival redness or
      roughness >2.0 units are unusual. The grading scale can be used successfully with
      decimal rather than integer scale increments. For experienced clinicians, a
      change in grade of > or =0.5 units may be significant.

PMID- 11233331
TI  - Comparison of the coulometric and polarographic measurement of a high-Dk
      hydrogel.
AB  - BACKGROUND: International Organization for Standardization (ISO) document ISO
      9913-1 details procedures for oxygen permeability coefficient (Dk) measurement of
      hydrogel contact lens materials up to 100 barrer. A draft ISO document 9913-2
      describing the coulometric technique states that the recommended procedures are
      suitable for nonhydrogel materials. New generation hydrogel lens materials exceed
      100 barrer, which is outside the scope of both documents. METHODS: A range of
      rigid gas-permeable materials from Dr. W. Benjamin's standard repository was used
      as a baseline to assess the accuracy of the polarographic and the coulometric
      methods. We also measured the permeability of a new generation hydrogel,
      lotrafilcon A, to explore the suitability of the polarographic and coulometric
      techniques for high-Dk hydrogel lenses. We modified equipment for both methods
      that incorporate several improvements including front surface masking to
      eliminate "edge effect." RESULTS: The coulometric technique provided results
      similar to those previously reported for the standard rigid gas-permeable
      materials and yielded relative standard errors typically <10%. The polarographic
      technique provided results similar to the accepted values for the standard rigid
      gas-permeable materials Dk <70 barrer only after the edge effect correction
      algorithm was applied. The polarographic results showed poor precision and
      significant, systematic differences from accepted values for the rigid gas
      permeables with Dk > 70 barrer. CONCLUSIONS: The coulometric method is preferable
      for the measurement of contact lens materials with permeability >70 barrer. The
      coulometric method was successfully modified to include hydrogels.

PMID- 11233332
TI  - An improved fluorophotometric method for tear turnover assessment.
AB  - PURPOSE: Scanning fluorophotometry is considered the "gold standard" to determine
      tear turnover rates (TTR). In this study, we attempted to improve the precision
      of basal TTR by fluorophotometry through a number of methodological changes.
      METHODS: By means of a timer program that produces audio cues, a new methodology
      that ensures confluence and a constant thickness of the tear film and
      minimization of reflex lacrimation as a result of the inhibition of the blink
      reflex was developed. This was compared with the standard protocol, both in a
      paired study and by a review of unpaired data. The minimum length of time
      required to monitor TTR measurements was also investigated. RESULTS: A
      significant improvement in correlation coefficient (r) of the log decay curve was
      observed as a result of changes in the protocol in both the paired (p = 0.016)
      and unpaired study (p < 0.0001). We determined that it was sufficient to monitor
      TTR for 10 min to obtain accurate results. CONCLUSIONS: We advocate that the
      changes be adopted as widely as possible for the precise and rapid measurement of
      basal tear turnover rates.

PMID- 11233333
TI  - The effect of refrigeration on the osmolality and pH of nonpreserved artificial
      tears containing carboxymethylcellulose.
AB  - INTRODUCTION: Nonpreserved artificial tears (NPAT) are a recommended treatment
      for dry eye. The manufacturers' instructions state to discard the container after
      initial opening and use. Some clinicians advocate the use and storage of NPAT in
      a zip-lock bag in a refrigerator for up to 12 h. The purpose of this study was to
      evaluate whether refrigeration of opened NPAT over a 12-h period had any effect
      on the pH or osmolality. METHODS: Forty individual carboxymethylcellulose NPAT
      samples were used in this study. The initial osmolality and pH of each sample
      were measured with a vapor pressure osmometer and electronic pH meter. The
      samples were refrigerated (4 degrees C) in closed zip-lock plastic bags for 12 h.
      After storage, the pH and osmolality of the samples were measured. The data were
      statistically analyzed for significant differences using a paired t-test.
      RESULTS: The mean initial pH and osmolality before refrigeration were 6.46 pH
      units and 304.10 mmol/kg, respectively. After refrigeration, the mean pH was 6.44
      units, and mean osmolality was 305.87 mmol/kg. Paired t-tests revealed a
      nonsignificant difference (p > 0.05) for both pH and osmolality. CONCLUSION:
      Refrigeration of opened carboxymethylcellulose NPAT stored in closed zip-lock
      plastic bags does not have a significant effect on the osmolality or pH of the
      solution. Storage of NPAT containing carboxymethylcellulose is an acceptable
      practice with regards to stability of pH and osmolality.

PMID- 11233334
TI  - Comparison of refractive state and circumferential morphology of retina, choroid,
      and sclera in chick models of experimentally induced ametropia.
AB  - PURPOSE: Simultaneous comparisons of the circumferential morphological tissue
      profiles and final refractions from form-deprivation myopia (FDM), defocus
      induced myopia (DIM), and defocus-induced hyperopia (DIH) models of ametropia
      have been made to test the hypothesis that changes in the thickness profiles of
      the three coats of the eye, and particularly that of the choroid, can be
      predicted from the degree of induced refractive error. METHODS: Hatchling
      chickens (n = 23) were raised for 2 weeks wearing either a monocular translucent
      diffuser (FDM, n = 8), monocular -10.00 D lens goggle (DIM, n = 7), monocular
      +10.00 D lens goggle (DIH, n = 7), or nothing (Norm, n = 1). All animals were
      refracted using retinoscopy and were then sacrificed, and whole eyes were
      processed for scanning electron microscopy. Retinal, choroidal, and cartilaginous
      sclera (CS) thickness measurements were made from photographic collages of the
      entire circumference of the globe. Of the 23 chickens, complete morphological
      profile data were available for both eyes of 10 animals (nine treated and one
      normal). The contralateral fellow eyes (FEyes) of all nine experimental chickens
      were used as experimental controls as paired comparisons for statistical
      analyses. RESULTS: Morphological profiles of control and experimental eyes
      revealed significant systematic regional variations in tissue thickness. This
      variation was related to nasal or temporal eccentricity with the nasal side
      generally thinner than the temporal. Retinal, choroidal, and CS tissue from FDM
      and DIM eyes showed very similar anatomical responses despite significantly
      different degrees of refractive change. DIH eyes showed significant increases in
      choroidal thickness but none in retinal or CS thickness. Analysis of fellow
      control eyes indicated that in both myopia models (FDM and DIM), significant
      changes in all tissues of the untreated fellow eyes occur whereas only the
      choroid of the fellow eye was affected in the hyperopic (DIH) model. CONCLUSIONS:
      The morphological similarity observed in the circumferential profiles of the
      retina, choroid, and cartilaginous sclera of the FDM and DIM eyes despite
      approximately 20 D difference in final refraction suggests that choroidal
      thickness is not a good predictor of final refractive error across models.
      Similarly, the final refractive difference of approximately 20 D between the DIM
      and the DIH eyes did not receive a major contribution from the final difference
      in choroidal thickness (with its implied effect on vitreous chamber length).

PMID- 11233335
TI  - How crowding affects letter confusion.
AB  - BACKGROUND: Acuity for letter recognition is known to be worse when multiple
      letters are presented with narrow interletter spacings than with wide spacings.
      How would interletter spacing affect the kind of errors made by human subjects?
      METHODS: Five-letter strings that were randomly drawn from the 26 uppercase
      letters of the English alphabet were presented foveally to the subjects. The
      interletter spacings were 1.0 and 0.1 letter height. Letter confusion matrices
      were constructed from the data collected using these spacing conditions. RESULTS:
      Narrow- and wide-spacing letter strings produced different letter confusion
      matrices. Aside from the letter confusions that were shared by both wide- and
      narrow-spacing strings, narrow-spacing strings produced more random confusions
      and a set of unique letter confusions, which was not observed under the wide
      spacing condition. CONCLUSION: Increased random guessing and lateral interactions
      between features of neighboring letters can account for most of the acuity
      deterioration observed under the narrow-spacing condition.

PMID- 11233336
TI  - Yes-no staircases with fixed step sizes: psychometric properties and optimal
      setup.
AB  - Interest in the use of adaptive staircase methods in clinical practice is
      increasing, but time limitations require that they be based on yes-no trials. The
      psychometric properties of yes-no staircases with fixed step sizes (FSS
      staircases) in small-sample situations have never been studied in depth. As a
      result, information is lacking as to what is the optimal setup for an FSS
      staircase. To determine this optimal setup, we used simulation techniques to
      study the asymptotic and small-sample convergence of yes-no FSS staircases as a
      function of the up/down rule, the size of the steps up or down, the starting
      stimulus level, the spread of the psychometric function, and the lapsing rate.
      Our results indicate that yes-no FSS staircases with steps up and down of the
      same size are unstable because with these settings, the staircases yield
      different results across variations in irrelevant parameters such as the spread
      of the psychometric function or the starting level. Our study also identified
      settings with which the properties of estimates are unaffected by these factors.
      With these optimal settings, yes-no FSS staircases can provide very quick and
      accurate estimates in 7 to 8 trials. Practical recommendations are given to get
      the best out of yes-no FSS staircases.

PMID- 11233338
TI  - The presumed influence of attention on accuracy in the Developmental Eye Movement
      (DEM) Test.

PMID- 11233337
TI  - Accommodation and induced with-the-rule astigmatism in emmetropes.

PMID- 11233339
TI  - Superior epithelial arcuate lesions with soft contact lens wear.
AB  - BACKGROUND: Superior epithelial arcuate lesions (SEALs) are an infrequent and
      often asymptomatic complication of conventional soft contact lens wear. The
      characteristic arcuate pattern of the full-thickness corneal epithelial lesion
      usually occurs in the area covered by the upper eyelid, within 2 to 3 mm of the
      superior limbus in the 10- and 2-o'clock region. METHODS: Literature on SEALs and
      recent clinical records from clinical trials using two types of prototype high Dk
      soft contact lenses were reviewed to gain greater insights into the etiology of
      SEALs. RESULTS AND CONCLUSIONS: The reported low incidence of SEALs is partly
      because SEALs are not usually symptomatic. The etiology of SEALs is
      multifactorial. Our current hypothesis is that SEALs are produced by mechanical
      chaffing at the peripheral cornea. This chaffing occurs as a result of inward
      pressure of the upper lid, in an area where the peripheral corneal topography and
      lens design, rigidity, and surface characteristics combine to create excessive
      "frictional" pressure and abrasive shear force on the epithelial surface. Patient
      characteristics such as gender, age, and specific corneal and lid topographies
      also appear to influence the occurrence of SEALs. Prototype silicone hydrogel
      lenses are made from higher modulus materials with surfaces that seem to differ
      subtly in wettability in some patients. The prevalence of SEALs may well increase
      with the first generations of these lenses.

PMID- 11233340
TI  - The health and controversial death of George Washington.

PMID- 11233341
TI  - Second malignant neoplasms of the head and neck in survivors of retinoblastoma.
AB  - Retinoblastoma is a malignant tumor of the embryonic retina. Although it is rare,
      it is the most common primary eye tumor of childhood. Life expectancy following
      treatment is now excellent, but survivors who have heritable retinoblastoma face
      an increased risk of a second malignant head or neck neoplasm. A second neoplasm,
      which often occurs in the irradiated field of the original tumor, has become the
      most significant threat to the survival of these patients. We report the case of
      a young girl who was cured of her retinoblastoma only to later develop a second
      nonocular tumor that metastasized to the superficial parotid gland. She underwent
      a superficial parotidectomy and neck dissection, but the malignancy eventually
      recurred and required further surgery and radiation therapy. In this article, we
      discuss the etiology, incidence, sites of occurrence, and management options for
      a second malignant neoplasm in retinoblastoma survivors. The head and neck
      surgeon must be vigilant in the diagnosis and management of second neoplasms in
      this patient population because they often occur in irradiated fields; surgical
      management is important to patient survival.

PMID- 11233342
TI  - Gabapentin for the treatment of tinnitus: a case report.
AB  - The objective of this article is to discuss the clinically effective use of
      gabapentin in patients with tinnitus. The author describes the case of a man who
      came to the office complaining of tinnitus of 10 months' duration. The patient
      was started on gabapentin and maintained on a regimen of 500 mg/day in divided
      doses. Subsequently, he reported that he was free of tinnitus approximately 23
      days a month and that he experienced a 75% decrease in symptoms during the
      remaining days. At 2 years' follow-up, he remains noise- and pain-free on 500
      mg/day of gabapentin.

PMID- 11233344
TI  - Problem we have experienced involves the oral mouth gag retractor geometry.

PMID- 11233343
TI  - Are we all just stupid?

PMID- 11233345
TI  - Nonobstructing exostoses of the external auditory canal.

PMID- 11233346
TI  - Endoscopic view of a high septal deviation.

PMID- 11233347
TI  - Multiple bilateral vocal fold cysts and recurrent pyogenic 'granuloma'.

PMID- 11233348
TI  - Electronystagmography in a blind patient with dizziness.

PMID- 11233350
TI  - Delayed endolymphatic hydrops: study and review of clinical implications and
      surgical treatment.
AB  - Delayed endolymphatic hydrops (DEH) differs from Meniere's disease in that it
      occurs in pre-existing ear pathology in patients who have a profound unilateral
      or total deafness that was caused by infection, trauma, or unknown causes during
      childhood or adulthood. We performed a retrospective review of 160 patients with
      ipsilateral, contralateral, or bilateral DEH. Eighty-seven patients who did not
      respond to medical therapy underwent surgical treatment. Our findings indicate
      that the more conservative surgical procedures--endolymphatic sac surgery,
      cochleosacculotomy, and streptomycin perfusion--are all as effective as and less
      destructive than labyrinthectomy for controlling vertigo. The clinical results of
      this study would seem to support the observations of others that DEH and
      Meniere's disease are related disorders caused predominantly by cases of viral
      labyrinthitis with unknown etiology.

PMID- 11233351
TI  - Extraintestinal Crohn's disease: case report and review of the literature.
AB  - Crohn's disease is a granulomatous inflammatory bowel disease. Its pathologic
      findings include noncontiguous chronic inflammation and noncaseating granulomas.
      Any segment of the gastrointestinal tract can be involved, but it is uncommon to
      find that Crohn's disease has spread beyond the intestine. We describe the case
      of a man with extraintestinal Crohn's disease that was marked by quiescent
      involvement of the lower gastrointestinal tract and florid involvement of the
      nasal cavity, supraglottic structures, glottis, and skin.

PMID- 11233349
TI  - Enchondroma of the petrous bone and parasellar area in Maffucci's syndrome.

PMID- 11233352
TI  - Just how integrated are integrated delivery systems? Results from a national
      survey.
AB  - This article examines three emergent processes in physician-hospital integrated
      delivery systems (IDSs). We find these processes are underdeveloped based on data
      gathered from a national sample of hospitals drawn from nine health care systems.
      These processes are also loosely coupled with the structures used to integrate
      physicians and hospitals, as well as with the environmental context in which they
      occur. Such loose coupling entails both advantages and disadvantages for IDSs.

PMID- 11233353
TI  - Identifying indicators of laboratory management performance: a multiple
      constituency approach.
AB  - The challenges for laboratory management posed by cost control, managed care,
      organizational restructuring, information networking and health system
      integration call for new measures to evaluate how effectively laboratories manage
      emerging performance expectations. This study identifies the Delphi panel method
      in achieving consensus on measures of effectiveness and considers a specific
      application, the identification of indicators of laboratory performance, from the
      perspective of key constituencies.

PMID- 11233354
TI  - Managing the care of health and the cure of disease--Part I: Differentiation.
AB  - The clinical methods used in health care and disease cure are easily understood.
      Yet when combined into institutions and broadened into social systems, the
      management of them becomes surprisingly convoluted. Part I of this article
      presents a framework to help understand how this happens.

PMID- 11233355
TI  - Understanding physicians' intentions to withdraw from practice: the role of job
      satisfaction, job stress, mental and physical health.
AB  - Health care organizations may incur high costs due to a stressed, dissatisfied
      physician workforce. This study proposes and tests a model relating job stress to
      four intentions to withdraw from practice mediated by job satisfaction and
      perceptions of physical and mental health.

PMID- 11233356
TI  - Managing the care of health and the cure of disease--Part II: Integration.
AB  - The development of appropriate levels of integration in the system of health care
      and disease cure will require stronger collective cultures and enhanced
      communication among the key actors. Part II of this paper uses this line of
      argument to reframe four major issues in this system: coordination of acute cure
      and of community care, and collaboration in institutions and in the system at
      large.

PMID- 11233357
TI  - Managing the care of health and the cure of disease: arguments for the importance
      of integration.

PMID- 11233358
TI  - A process for delivering bad news: supporting families when a child is diagnosed.
AB  - A process for delivering bad news to families of children with a
      neurodegenerative disorder was developed to enhance the families' coping
      abilities and to lessen the impact of the devastating news. Its creation was
      guided by a review of the literature on parental satisfaction with and
      preferences for diagnosis delivery, published guidelines for breaking bad news,
      and the concepts of coping, grief, support, hope, and family-centered care.
      Nurses play a collaborative role in the implementation of this process that
      remains sensitive to the needs of each family. Their influence on how the
      interaction takes place and their support of the family both during and after
      they receive bad news are pivotal. Research to formally evaluate the outcomes of
      the interventions and strategies within the process is necessary.

PMID- 11233359
TI  - Apomorphine in the treatment of Parkinson's disease.
AB  - Apomorphine is a potent, nonselective, direct-acting dopamine-receptor agonist.
      Given subcutaneously, it has a rapid onset of antiparkinsonian action
      qualitatively comparable to that of levodopa. Despite its long history, it was
      not until peripheral dopaminergic side effects could be controlled by oral
      domperidone that the clinical usefulness of apomorphine in Parkinson's disease
      began to be investigated thoroughly in the mid-1980s. Although several routes
      have been tried, subcutaneous administration, either as intermittent injections
      or continuous infusion, is so far the best and most applied in the treatment of
      advanced, fluctuating Parkinson's disease. Clinical trials have shown stable
      efficacy with markedly reduced time spent in "off" phases as well as, for
      infusion therapy, reduced levodopa requirements. In the most successful cases,
      motor fluctuations disappear and the need for oral medication is eliminated.
      Adverse events are usually mild and dominated by cutaneous reactions.
      Neuropsychiatric side effects occur, but the influence of apomorphine on these
      remains controversial. Controlled long-term clinical trials are highly warranted
      to reveal the full potentials of this treatment. Careful patient selection and
      follow-up, where the specialized movement disorder nurse has a crucial role, are
      paramount for a successful long-term outcome. Apomorphine warrants a wider
      application in the treatment of advanced Parkinson's disease and should be tried
      before more invasive interventions are considered.

PMID- 11233360
TI  - Epidemiology of intracranial aneurysm and subarachnoid hemorrhage.
AB  - Intracranial aneurysmal hemorrhage is a common but devastating condition
      associated with significant morbidity and mortality. Epidemiologic studies have
      identified risk factors associated with this condition. Genetic factors involve
      family history and the presence of certain heritable connective tissue disorders
      such as Ehlers-Danlos syndrome, Marfan's syndrome, neurofibromatosis, and
      polycystic kidney disease. Acquired factors include traumatic brain injury,
      sepsis, smoking, and hypertension. Management of these patients consists of
      prevention, patient screening, and prophylactic aneurysm repair.

PMID- 11233361
TI  - Evaluation of the Neuroscience Nurse Internship Program: the first decade.
AB  - This article describes the evaluation of the Neuroscience Nurse Internship
      Program (NNIP). The NNIP was initiated in 1988 by the National Institutes of
      Health Clinical Center to meet the demand for highly skilled nurses to care for
      persons with nervous system disorders. To determine whether the program was
      meeting its goals, an evaluation component was incorporated into the program. The
      evaluation process was based on the RSA Model of Continuing Education for
      nursing. The RSA model consists of four basic components, three of which were
      included in the assessment of the NNIP--process, content, and outcome. The
      evaluation revealed that the nurse-interns were satisfied with the lectures and
      clinical content of the program. Moreover, the nurse-interns improved their
      knowledge of neuroscience nursing and their confidence in performing neuroscience
      nursing skills. Information from the evaluation was used to modify the structure
      of the program and to refine lecture content and clinical requirements.

PMID- 11233362
TI  - Teaching acute care nurses cognitive assessment using LOCFAS: what's the best
      method?
AB  - The Levels of Cognitive Functioning Assessment Scale (LOCFAS) is a behavioral
      checklist used by nurses in the acute care setting to assess the level of
      cognitive functioning in severely brain-injured patients in the early post-trauma
      period. Previous research studies have supported the reliability and validity of
      LOCFAS. For LOCFAS to become a more firmly established method of cognitive
      assessment, nurses must become familiar with and proficient in the use of this
      instrument. The purpose of this study was to find the most effective method of
      instruction by comparing three methods: a self-directed manual, a teaching video,
      and a classroom presentation. Videotaped vignettes of actual brain-injured
      patients were presented at the end of each training session, and participants
      were required to categorize these videotaped patients by using LOCFAS. High
      levels of reliability were observed for both the self-directed manual group and
      the teaching video group, but an overall lower level of reliability was observed
      for the classroom presentation group. Examination of the accuracy of overall
      LOCFAS ratings revealed a significant difference for instructional groups; the
      accuracy of the classroom presentation group was significantly lower than that of
      either the self-directed manual group or the teaching video group. The three
      instructional groups also differed on the average accuracy of ratings of the
      individual behaviors; the accuracy of the classroom presentation group was
      significantly lower than that of the teaching video group, whereas the self
      directed manual group fell in between. Nurses also rated the instructional
      methods across a number of evaluative dimensions on a 5-point Likert-type scale.
      Evaluative statements ranged from average to good, with no significant
      differences among instructional methods.

PMID- 11233363
TI  - Camp experiences and attitudes toward epilepsy: a pilot study.
AB  - Most healthcare providers report anecdotally that a camping experience helps
      children and adolescents with chronic health conditions to develop more positive
      attitudes toward their condition. However, children's and adolescents'
      perceptions have rarely been studied systematically. This pilot study of 20
      campers with epilepsy who were 8-16 years of age was undertaken to examine the
      effect of a camp experience on their attitudes toward epilepsy. Attitudes,
      measured by the 13-item Child Attitude Toward Illness Scale (CATIS), were
      assessed before and after the camp experience. No pretest or posttest difference
      in attitude toward epilepsy was found in the total group. However, when attitudes
      were examined by seizure frequency, there was a trend for those with more
      frequent seizures to report a more positive attitude after the camp experience.
      Issues in evaluating camp experiences for youth with chronic conditions are
      reviewed, and recommendations are made for a comprehensive camp evaluation.
      Nurses are encouraged to assist families whose child is challenged by more
      frequent seizures to consider a camp experience.

PMID- 11233364
TI  - Overview of migraine.
AB  - Migraine, one of the most common incapacitating headaches, afflicts 23 million
      adults in the United States. There is a controversy in the literature on the
      theoretical perspective of migraine, the efficacy of treatment strategies,
      measurement, and correlates. Thus, more research is needed on these issues. A
      wide range of treatments is available for migraine. In addition to terminating
      migraine headache, appropriate migraine care includes preventing its attacks and
      improving patients' quality of life by administrating pharmacologic preparations
      in conjunction with a variety of alternative methods.

PMID- 11233365
TI  - ELSO: new life for the life sciences in Europe.

PMID- 11233366
TI  - Molecular recognition of disease at natural killer cell immune synapses.
AB  - An emerging theme in contemporary molecular immunology is that a knowledge of
      protein structures and the physical chemistry of soluble receptor/ligand pairs is
      insufficient to predict the outcome of intercellular communication. Cell surface
      receptors need to be considered as part of supramolecular complexes of proteins
      and lipids that facilitate specific receptor conformations and distinct
      distributions at cell surfaces. As cells of the immune system survey other cells
      for signatures of disease, proteins accumulate and organise in distinct patterns
      at the contact regions between the cells. The intercellular organisation of
      proteins by which a cell's state of health is relayed has been termed the immune
      or immunological synapse. That different arrangements of segregated protein
      domains can occur at immune synapses raises a number of important questions. For
      example does supramolecular organisation of the synapse influence the outcome of
      the intercellular communication and how is the organisation of protein at immune
      synapses biophysically controlled?

PMID- 11233367
TI  - Endurance and the ACE I/D polymorphism.
AB  - A variant of the angiotensin-converting enzyme (ACE) gene, which we all carry, is
      known as the insertion, or I allele, due to the presence of a 287 base pair DNA
      fragment. This variant, or polymorphism, is associated with reduced levels of
      serum and tissue ACE. This intriguing polymorphism has been associated with
      various physiological and pathological states from diabetic renal disease to
      coronary heart disease. There have been conflicting reports regarding its
      association with some aspects of enhanced endurance performance in elite
      athletes. This review aims to examine the evidence for and against an association
      of the I allele with endurance and highlight some of the possible mechanism that
      might be involved. It is concluded that an association seems likely and that it
      is probably due to a local muscle effect rather than a central cardiorespiratory
      mechanism.

PMID- 11233368
TI  - The space debris around the earth.

PMID- 11233369
TI  - Legume root nodule bacteria and acid pH.
AB  - In 1984 the Australian Wool Research Trust Fund called for expressions of
      interest in projects directed at using the developing techniques of molecular
      biology for application to agricultural problems. With our interests in legume
      root nodule bacteria and their physiology, we felt that the problems for legume
      nodulation and N2 fixation posed by soils which were already acid, or which were
      rapidly acidifying, required just such attention. Further, the finding body's
      request coincided with the highly successful introduction into Western Australian
      agriculture of acid-tolerant strains of the medic-nodulating bacteria
      Sinorhizobium meliloti originating from acid soils on Sardinia (see below). The
      existence of such strains made it obvious that acid tolerance was a genetically
      determined trait, and provided invaluable biologically diverse material with
      which to work. The biological bases for that trait of acid tolerance were totally
      obscure, and many remain so, but the following account provides some light in the
      darkness. The research that we have done since in pursuit of explanations for
      acid tolerance have been funded first by the Wool Research Trust Fund and the
      Rural Credits Development Fund, and later by the Australian Research Council, and
      we here record our appreciation for their support.

PMID- 11233370
TI  - Artificial nutrition and hydration in the patient with advanced dementia: is
      withholding treatment compatible with traditional Judaism?
AB  - Several religious traditions are widely believed to advocate the use of life
      sustaining treatment in all circumstances. Hence, many believe that these faiths
      would require the use of a feeding tube in patients with advanced dementia who
      have lost interest in or the capacity to swallow food. This article explores
      whether one such tradition--halachic Judaism--in fact demands the use of
      artificial nutrition and hydration in this setting. Traditional (halachic)
      arguments have been advanced holding that treatment can be withheld in persons
      who are dying, in individuals whose condition causes great suffering, or in the
      event that the treatment would produce suffering. Individuals with advanced
      dementia can be considered to be dying, often suffer as a result of their
      dementia, and are likely to suffer from the use of a feeding tube. Given these
      observations and the absence of a compelling case for distinguishing between tube
      feeding and other forms of medical treatment, traditional Judaism appears
      compatible with withholding artificial nutrition for individuals with advanced
      dementia.

PMID- 11233371
TI  - Intuitions, principles and consequences.
AB  - Some approaches to the assessment of moral intuitions are discussed. The
      controlled ethical trial isolates a moral issue from confounding factors and
      thereby clarifies what a person's intuition actually is. Casuistic reasoning from
      situations, where intuitions are clear, suggests or modifies principles, which
      can then help to make decisions in situations where intuitions are unclear. When
      intuitions are defended by a supporting principle, that principle can be tested
      by finding extreme cases, in which it is counterintuitive to follow the
      principle. An approach to the resolution of conflict between valid moral
      principles, specifically the utilitarian and justice principles, is considered.
      It is argued that even those who justify intuitions by a priori principles are
      often obliged to modify or support their principles by resort to the
      consideration of consequences.

PMID- 11233372
TI  - Professional recommendations: disclosing facts and values.
AB  - It is not unusual for patients and their families, when confronted with difficult
      medical choices, to ask their physicians for advice. This paper outlines the
      shades of meaning of two questions frequently put to physicians: "What should I
      do?" and "What would you do?" It is argued that these are not questions about
      objective matters of fact. Hence, any response to such questions requires an
      understanding, appreciation, and disclosure of the personal context and values
      that inform the recommendation. A framework for considering and articulating a
      response to these questions is suggested, using as a heuristic the phrasing "If I
      were you.../If it were me...".

PMID- 11233373
TI  - Balancing rationalities: gatekeeping in health care.
AB  - Physicians are increasingly confronted with the consequences of allocation
      policies. In several countries, physicians have been assigned a gatekeeper role
      for secondary health care. Many ethicists oppose this assignment for several
      reasons, concentrating on the harm the intrusion of societal arguments would
      inflict on doctor-patient relations. It is argued that these arguments rest on a
      distinction of spheres of values and of rationality, without taking into account
      the mixing of values and rationalities that takes place in everyday medical
      practice. If medical practice, then, does not follow a single, pure rationality,
      can it also incorporate the societal rationality of the gatekeeper role? Using a
      case from general practice, I try to show how physicians may integrate societal
      arguments into their practice in a morally acceptable way. A version of the model
      of reflective equilibrium and especially Beauchamp and Childress's safeguards,
      may be helpful both to analyse and teach such balancing of values and
      rationalities.

PMID- 11233374
TI  - Imposed separation of conjoined twins--moral hubris by the English courts?

PMID- 11233375
TI  - Shifting ethics: debating the incentive question in organ transplantation.
AB  - The paper reviews the discussion within transplantation medicine about the organ
      supply and demand problem. The focus is on the evolution of attitudes toward
      compensation plans from the early 1980s to the present. A vehement rejection on
      ethical grounds of anything but uncompensated donation--once the professional
      norm--has slowly been replaced by an open debate of plans that offer financial
      rewards to persons willing to have their organs, or the organs of deceased kin,
      taken for transplantation. The paper asks how this shift has occurred and what it
      tells us about the dynamics of bioethical debates, both within professional
      circles and in wider public arenas.

PMID- 11233377
TI  - When is surgery research? Towards an operational definition of human research.
AB  - The distinction between clinical practice and surgical research may seem trivial,
      but this distinction can become a complex issue when innovative surgeries are
      substituted for standard care without patient knowledge. Neither the novelty nor
      the risk of a new surgical procedure adequately defines surgical research. Some
      institutions tacitly allow the use of new surgical procedures in series of
      patients without informing individuals that they are participating in a
      scientific study, as long as no written protocol or hypothesis exists.
      Institutions can justify this practice by viewing human research in narrow terms
      as an activity outlined in a formal protocol. Application of limited definitions,
      however, erodes patients' rights and risks losing public confidence in how
      biomedical research is conducted. I propose an operational definition of human
      research also be recognised. Enforcing more rigid and less ambiguous guidelines
      of human research may curtail enrolment into some studies, but it will also
      protect patients from being used as subjects without their knowledge.

PMID- 11233376
TI  - Psychiatric disorders and fitness to drive.
AB  - OBJECTIVE: In Switzerland, as in some other European countries, medical doctors
      may breach patient confidentiality and report to police authorities any patient
      who seems prone to automobile accidents or traffic violations. The aim of this
      study was to see if those patients reported to authorities actually represent a
      higher risk than drivers not reported to the police. DESIGN: This study was
      designed following a case-control study comparing the characteristics of a group
      of psychiatric patients who were reported to authorities for preventive purposes,
      with the characteristics of another group of people who had disorders that were
      noticed at the time of an accident or traffic violation. RESULTS: The results
      show that medical doctors tended to report male patients, patients with a low
      level of education, and patients with a severe psychiatric background. The
      subjects of the control group, who had often been involved in accidents or
      committed traffic violations in the past, did not possess these characteristics.
      CONCLUSIONS: The breach of medical confidentiality by doctors in reporting to
      authorities patients who are allegedly at risk is ethically questionable as long
      as the evaluation of driving performance does not rely on objective bases.

PMID- 11233378
TI  - How should doctors approach patients? A Confucian reflection on personhood.
AB  - The modern doctor-patient relationship displays a patient-centred, mutual
      participation characteristic rather than the former active-passive or guidance
      cooperation models in terms of medical decision making. Respecting the wishes of
      patients, amounting to more than mere concern for their welfare, has become the
      feature central to certain modern bioethics theories. A group of ethical
      principles such as respect for autonomy, beneficence, non-maleficence, and
      justice has been proposed by bioethicists and widely adopted by many medical
      societies as an ethical guide to how doctors, in their daily practice, should
      treat their patients. However, seeing patients as persons who are rational, self
      conscious beings capable of valuing their own lives, and who are consequently
      entitled to the liberty and rights to choose for themselves, is in general the
      backbone of Western bioethical principles. Since Confucian philosophy has long
      been a representative of the East-Asia cultural tradition and Confucian bioethics
      has recently been developed as a theory of applied ethics, examining Confucius's
      idea of "persons" may shed some light on the current bioethical debates.
      Confucius's concept of persons, which is best interpreted via his theories of
      "chun-tze", (the morally ideal person) encapsulating a two-dimensional approach,
      (the "autonomous person" and the "relational person"), provides a more
      comprehensive model regarding what a person is and how he/she should be treated.
      This two-dimensional approach sees a person not only as a rational, autonomous
      agent but also as a relational, altruistic identity whose self actualisation
      involves incessant participating in and promoting of the welfare of his fellow
      persons. Hence this may balance the current bioethical trend whereby "respect for
      autonomy" often triumphs.

PMID- 11233379
TI  - Neonatal euthanasia: moral considerations and criminal liability.
AB  - Despite tremendous advances in medical care for critically ill newborn infants,
      caregivers in neonatal intensive care units still struggle with how to approach
      those patients whose prognoses appear to be the most grim, and whose treatments
      appear to be the most futile. Although the practice of passive neonatal
      euthanasia, from a moral perspective, has been widely (albeit quietly) condoned,
      those clinicians and families involved in such cases may still be found legally
      guilty of child abuse or even manslaughter. Passive neonatal euthanasia remains
      both a moral dilemma and a legal ambiguity. Even the definition of passive
      euthanasia remains unclear. This manuscript reviews the basic moral and legal
      considerations raised by the current practice of neonatal euthanasia, and
      examines the formal position statements of the American Medical Association and
      the American Academy of Pediatrics. The paper concludes by emphasising the need,
      at least in the United States, to clarify the legal status of this relatively
      common medical practice.

PMID- 11233380
TI  - Developing a culturally relevant bioethics for Asian people.
AB  - Because of cultural differences between East and West, any attempt at outright
      adaptation of Western ideas in Asia will undoubtedly encounter problems, if not
      rejection. Transferring an idea from one place to another is just like
      transplanting an organ from a donor to a recipient--rejection is to be expected.
      Human cultures respond to new ideas from different value systems in very much the
      same way. Recently, biomedical ethics has received much attention in Asia.
      Fundamental advances in medicine have motivated medical scientists to look at the
      ethical issues arising from this progress. Will the principles upheld by the
      bioethicists in the West meet the challenge in Asia? This article argues that
      Asian bioethicists must develop a bioethics responding to their own cultural
      contexts. If Western principles are adopted, then they must be re-interpreted and
      even modified, if necessary, in light of Asian beliefs.

PMID- 11233381
TI  - Words of Tohkaku Wada: medical heritage in Japan.
AB  - The origins of Japan's medical ideas, which are deeply rooted in its religion,
      culture and history, are not widely understood in medical societies of other
      countries. We have taken up the task of summarising this tradition here so that
      some insight can be gained into the unique issues that characterise the practice
      of medicine in Japan. We borrow from the sayings of Tohkaku Wada, a medical
      philosopher of late eighteenth-century Japan, for a look at Japanese medical
      tradition. Wada's medical thought was very much reflective of the Buddhism, Zen,
      and swordsmanship that informed eighteenth-century philosophy in Japan. His
      central concepts were "chu" and "sei", that is, complete and selfless dedication
      to the patient and the practice of medicine. This paper explores Wada's thought,
      explaining it mainly from the standpoint of Japanese traditional culture.

PMID- 11233382
TI  - Is consent in medicine a concept only of modern times?
AB  - Although the issue of consent in medical practice has grown immensely in recent
      years, and it is generally believed that historical cases are unknown, our
      research amongst original ancient Greek and Byzantine historical sources reveals
      that it is a very old subject which ancient philosophers and physicians have
      addressed. Plato, in ancient Greece, connected consent with the quality of a free
      person and even before him, Hippocrates had advocated seeking the patient's
      cooperation in order to combat the disease. In Alexander the Great's era and
      later on in Byzantine times, not only was the consent of the patient necessary
      but physicians were asking for even more safeguards before undertaking a
      difficult operation. Our study has shown that from ancient times physicians have
      at least on occasion been driven to seek the consent of their patient either
      because of respect for the patient's autonomy or from fear of the consequences of
      their failure.

PMID- 11233383
TI  - Cardiopulmonary resuscitation ethics: a response to Michael Ardagh.

PMID- 11233384
TI  - Informed consent.

PMID- 11233385
TI  - Prazosin GITS vs sustained release nifedipine in patients with hypertension and
      abnormal lipid profile: a randomized, controlled, multicenter study. Madras
      Hypertension Study Group.
AB  - OBJECTIVE: To compare the long-term antihypertensive efficacy, tolerability, and
      metabolic effects of prazosin GITS and a sustained release (SR) preparation of
      nifedipine. DESIGN: Randomized, controlled, multicenter study of 26 weeks
      duration. SETTING: Office practices of 24 physicians in Chennai, Tamil Nadu,
      India. PATIENTS: Males and females, aged 30 to 70 yrs, with hypertension of JNC V
      stage 1 or 2 at the end of a 2-week placebo run-in period, and an abnormal lipid
      profile. Sufficient number of patients recruited so that at least 60 complete the
      entire study. INTERVENTIONS: Prazosin GITS (Minipress XL, 2.5-5 mg once daily) or
      sustained release nifedipine (Nicardia Retard 10-20 mg twice daily) for upto 6
      weeks, continued upto 24 weeks in those showing a pre-defined response (SBP
      and/or DBP normalized, or DBP fall of at least 10 mm Hg with actual value of DBP
      < 95 mm Hg). Patients allocated to either of the two interventions by
      randomization. OUTCOME MEASURES: Percent patients showing pre-defined BP response
      at week 6; percent patients with DBP < 90 mm Hg, SBP < 140 mm Hg, and both;
      percent patients with DBP fall > or = 10 mm Hg; mean fall in BP among those
      receiving treatment for 24 weeks; mean change in blood glucose and serum lipids
      at the end of weeks 8, 16, and 24 of treatment; frequency and intensity of
      adverse events judged probably or definitely related to the drug. RESULTS: 54
      patients randomized to prazosin GITS group and 52 to nifedipine SR group. Of
      these, 39 in prazosin GITS group (M 23, F 16; mean age-50. 6 yr, SEM 1.66) and 36
      in nifedipine SR group (M 20, F 16; mean age-52.3 yr, SEM 1.71) completed the
      study. Percent patients with DBP < 90 mm Hg at 24 weeks: prazosin GITS--100%,
      nifedipine SR--100%; SBP < 140 mm Hg: prazosin GITS--94.9%, nifedipine SR--91.7%;
      both DBP < 90 mm Hg and SBP < 140 mm Hg: prazosin GITS--92.3%, nifedipine SR-
      91.7%; percent patients with DBP fall of 10 mm Hg or more at 24 weeks: prazosin
      GITS--76.9%, nifedipine SR--83.3%. The mean fall in the systolic and diastolic
      blood pressure from the end-of-placebo-phase values to all the other time points
      was comparable in the 2 groups. Treatment with prazosin GITS did not produce any
      statistically or clinically significant change in the metabolic parameters at the
      end of 24 weeks, while with nifedipine SR there was a significant increase in the
      serum LDL values at 24 weeks (p = 0.009). Adverse events probably or definitely
      related to the drug: prazosin GITS--1.9%, nifedipine SR--2.1%. CONCLUSION: Both
      drugs were equally effective and well tolerated. While prazosin GITS was neutral
      on serum lipids, use of nifedipine SR was associated with a significant increase
      in serum LDL cholesterol at the end of 24 weeks.

PMID- 11233387
TI  - A randomized, controlled, multicenter study to compare prazosin GITS with
      enalapril in hypertensive patients with diabetes mellitus. Bombay Hypertension
      Study Group.
AB  - OBJECTIVE: To compare the long-term antihypertensive efficacy, tolerability, and
      metabolic effects of prazosin GITS and enalapril. DESIGN: Randomized, controlled,
      multicenter study of 26 weeks duration. SETTING: Office practices of 20
      physicians in Mumbai, India. PATIENTS: Males and females, aged 30 to 70 yrs, with
      hypertension of JNC V stage 1 or 2 at the end of a 2-week placebo run-in period,
      and diabetes mellitus with at least acceptable glycaemic control (FBS < or = 140
      mg/dl, 2-hr PMBS < or = 200 mg/dl, and glycosylated hemoglobin < or = 9.5%).
      Sufficient number of patients recruited so that at least 60 complete the entire
      study. INTERVENTIONS: Prazosin GITS (Minipress XL, 2.5-5 mg once daily) or
      enalapril (Enam, 5-10 mg once daily) for upto 6 weeks; continued upto 24 weeks in
      those showing a pre-defined response (SBP and/or DBP normalized, or DBP fall of
      at least 10 mm Hg with actual value of DBP < 95 mm Hg). Patients allocated to
      either of the two interventions by randomization. OUTCOME MEASURES: Percent
      patients showing pre-defined BP response at week 6; percent patients with DBP <
      90 mm Hg, SBP < 140 mm Hg, and both; percent patients with DBP fall > or = 10 mm
      Hg; mean fall in BP among those receiving treatment for 24 weeks; mean change in
      serum lipids at the end of weeks 8, 16, and 24 of treatment; mean change in blood
      sugar and glycosylated hemoglobin at the end of weeks 8, 16, and 24 of treatment;
      mean change in 12-hr urinary microalbuminuria and laboratory parameters for
      safety at the end of week 24; frequency and intensity of adverse events judged
      probably or definitely related to the drug. RESULTS: Forty-Eight patients
      randomized to prazosin GITS group and 41 to enalapril group. Of these, 31 in
      prazosin GITS group (M 19, F 12; mean age-53.4 yr, SEM 1.68) and 29 in enalapril
      group (M17, F 12; mean age-54.7 yr, SEM 1.64) completed the entire study. Percent
      patients with DBP < 90 mm Hg at 24 weeks: prazosin GITS--71.0%, enalapril--72.4%;
      SBP < 140 mm Hg: prazosin GITS--54.8%, enalapril--55.2; both DBP < 90 mm Hg and
      SBP < 140 mm Hg: prazosin GITS--54.8%, enalapril--44.8%; percent patients with
      DBP fall of 10 mm Hg or more at 24 weeks: prazosin GITS--77.4%, enalapril--72.4%.
      The mean fall in the systolic and diastolic blood pressure from the end-of
      placebo-phase values to all the other time points was comparable in the two
      groups. Treatment with prazosin GITS resulted in a favourable effect on serum
      triglycerides at the end of 8 weeks (p = 0.017) and 16 weeks (p = 0.011), and no
      detrimental effect or a marginal beneficial effect on total cholesterol, HDL
      cholesterol, and LDL cholesterol. Enalapril group, on the other hand, showed a
      significant increase in LDL cholesterol at the end of 24 weeks (p = 0.018), and a
      marginal increase in total cholesterol, but a beneficial effect on triglycerides
      at the end of 16 weeks (p = 0.015). Neither drug had any effect on glycosylated
      hemoglobin and 12-hr urinary microalbuminuria. Treatment with both drugs was
      associated with an increase in FBS and 2-hr PMBS, but this rise reached
      statistical significance only in prazosin GITS group. Adverse events probably or
      definitely related to the drug: prazosin GITS--2 of 44 patients (4.5%), enalapril
      -6 of 39 patients (15.4%). CONCLUSION: 1. In the doses used, prazosin GITS showed
      comparable antihypertensive efficacy to enalapril. 2. While enalapril had
      variable effect, prazosin GITS showed a consistent beneficial effect on some of
      the serum lipid fractions. 3. The 3-fold difference in the incidence of side
      effects, although not statistically significant for the available sample size,
      may be clinically relevant.

PMID- 11233386
TI  - Prazosin GITS vs atenolol in patients with hypertension and normal lipid profile:
      a randomized, controlled multicenter study. Hyderabad Hypertension Study Group.
AB  - OBJECTIVE: To compare the long-term antihypertensive efficacy, tolerability, and
      metabolic effects of prazosin GITS and atenolol. DESIGN: Randomized, controlled,
      multicenter study of 26 weeks duration. SETTING: Office practices of 24
      physicians in Hyderabad, Andhra Pradesh, India. PATIENTS: Males and females, aged
      30 to 70 yrs, with hypertension of JNC V stage 1 or 2 at the end of a 2-week
      placebo run-in period, and a normal lipid profile. Sufficient number of patients
      recruited so that at least 60 complete the entire study. INTERVENTIONS: Prazosin
      GITS (Minipress XL, 2.5-5 mg once daily) or atenolol (Tenormin 50-100 mg once
      daily) for upto 6 weeks, continued upto 24 weeks in those showing a pre-defined
      response (SBP and/or DBP normalized, or DBP fall of at least 10 mm Hg with actual
      value of DBP < 95 mm Hg). Patients allocated to either of the two interventions
      by randomization. OUTCOME MEASURES: Percent patients showing pre-defined BP
      response at week 6; percent patients with DBP < 90 mm Hg, SBP < 140 mm Hg, and
      both; percent patients with DBP fall > or = 10 mm Hg; mean fall in BP among those
      receiving treatment for 24 weeks; mean change in serum lipids at the end of weeks
      8, 16, and 24 of treatment; mean change in laboratory parameters for safety at
      the end of week 24; frequency and intensity of adverse events judged probably or
      definitely related to the drug. RESULTS: 62 patients randomized to prazosin GITS
      group and 60 to atenolol group. Of these, 39 in prazosin GITS group (M 23, F 16;
      mean age-48.4 yr, SEM 1.60) and 39 in atenolol group (M 24, F 15; mean age-42.9
      yr, SEM 1.48) completed the entire study. Percent patients with DBP < 90 mm Hg at
      24 weeks: prazosin GITS--92.3%, atenolol--92.3%; SBP < 140 mm Hg: prazosin GITS-
      89.7% atenolol--94.9% both DBP < 90 mm Hg and SBP < 140 mm Hg: prazosin GITS-
      87.2%, atenolol--89.7%; percent patients with DBP fall of 10 mm Hg or more at 24
      weeks: prazosin GITS--92.3%, atenolol--100%. The mean fall in the systolic and
      diastolic blood pressure from the end-of-placebo-phase values to all the other
      time points was comparable in the 2 groups, except at week 2, when the fall was
      greater for atenolol (8.8 mm Hg vs 11.4 mm Hg, p = 0.05). Treatment with prazosin
      GITS resulted in a favourable effect on the serum lipid profile at the end of 24
      weeks (p = 0.02 for total cholesterol, p = 0.015 for the ratio of total to HDL
      cholesterol, p = 0.04 for LDL cholesterol). Atenolol, on the other hand, did not
      produce any significant change in the metabolic parameters at the end of 24
      weeks. Adverse events probably or definitely related to the drug: prazosin GITS-
      in 10.3% patients, atenolol--in 16.7% patients. CONCLUSION: In the doses used,
      both prazosin GITS and atenolol had comparable efficacy and tolerability. While
      atenolol was neutral on serum lipids, prazosin GITS showed a beneficial effect at
      the end of 24 weeks.

PMID- 11233388
TI  - The new millenium is a period of expectation and uncertainty for paediatric
      cardiac services.

PMID- 11233389
TI  - The left-sided aortic arch in humans, viewed as the end-result of natural
      selection during vertebrate evolution.
AB  - At some point during vertebrate evolution from species dwelling in water to
      living on land, the ancestral double or right aortic arches became single and
      left-sided in mammals, including humans, as the result of synchronous
      developments in cardiovascular and respiratory embryogenesis. Since left-sided
      aortic arches are unique to mammals, hemodynamics related to the placenta,
      specifically the requirement for a large arterial duct connecting to the
      descending aorta, may have led to switching from the right-sided to the left
      sided arch. Additionally, development of a trilobar right lung and its bronchial
      tree, also unique to mammalian evolution, restricted the space above the high
      eparterial bronchus to a single large vessel. Consequently, mammals that mutated
      to the left-sided aortic arch avoided respiratory, digestive or circulatory
      problems that are often associated with an isolated right-sided aortic arch-
      something which could be considered a successful mistake. Due to natural
      selection, and survival of the fittest, the left-sided arch became the norm in
      mammals. In congenital cardiac malformations where a large arterial duct is not
      mandatory in fetal life, as in Fallot's tetralogy or common arterial trunk, a
      right-sided aortic arch continues to occur, perhaps as an atavistic reversion to
      the anatomy seen in ancestral vertebrates.

PMID- 11233390
TI  - Anatomic biventricular repair by intraatrial and intraventricular re-routing in
      patients with left isomerism.
AB  - OBJECTIVE: To determine the efficacy of anatomic biventricular repair by a
      combination of intraatrial and intraventricular re-routing in patients with
      isomerism of the left atrial appendages. METHODS: Anatomic biventricular repair
      by means of combined intraratrial and intraventricular re-routing was achieved in
      5 of the 63 patients with left isomerism in whom we attempted a definitive
      surgical procedure. The inferior caval vein was interrupted in 3. The Mustard
      procedure was chosen for intraatrial redirection of blood in 4, and the Senning
      procedure in the other. Intraventricular re-routing was carried out via a right
      ventriculotomy in all patients, using an external conduit to reconstruct the
      morphologically right ventricular outflow tract. RESULTS: One patient died one
      month after the procedure because of low cardiac output and bronchial bleeding.
      Obstruction across the superior caval venous channel occurred after the Senning
      procedure in this particular patient, related to the interrupted inferior caval
      vein draining via the azygous vein. The other 4 patients are currently doing
      well. Postoperative catheterization showed excellent cardiac performance, with no
      obstruction across the venous channels or the ventricular outflow tracts in these
      4. No episode of significant arrhythmia has been noted, all patients having a
      regular atrial rhythm, although the P wave vector was unusual in each patient.
      Reoperation has been needed thus far in one patient, 128 months after the initial
      repair, because of obstruction of the external conduit. CONCLUSION: With precise
      recognition of the morphologic features, a combination of intraatrial and
      intraventricular re-routing can successfully be established in patients with
      isomeric left atrial appendages, with functional results in the intermediate term
      being reasonable.

PMID- 11233391
TI  - Rupture of pulmonary aneurysms in association with long-standing Waterston
      shunts.
AB  - Anastomosis of the ascending aorta to the right pulmonary artery, the so-called
      Waterston shunt, was undertaken as a palliative procedure for children with
      cyanotic congenital heart disease due to obstruction of the pulmonary outflow
      tract with reduced pulmonary blood flow. We present the clinicopathological
      correlations in two patients who underwent construction of Waterston shunts as
      neonates, and subsequently died of ruptured pulmonary aneurysms in adult life.
      Rupture should, therefore, be recognized as a late complication of this
      procedure, and be considered in the long-term follow-up of such patients,
      especially when the shunted lung is hypertensive.

PMID- 11233392
TI  - Long-term assessment and serial evaluation of cardiorespiratory exercise
      performance and cardiac function in patients with atrial switch operation for
      complete transposition.
AB  - BACKGROUND: At present, a considerable number of patients survive who underwent
      an atrial switch operation for correction of complete transposition. Our study
      aimed to assess their long-term exercise performance and the serial evolution of
      cardiac function. METHODS: We studied 22 patients 5 to 17 years after an atrial
      switch operation, and followed them serially for 3.5 +/- 2 years after the first
      evaluation. Cardiorespiratory exercise function was assessed by analysis of gas
      exhange and by determination of the ventilatory anaerobic threshold.
      Echocardiography was performed on all evaluations. RESULTS: All patients were in
      Class I of the classification of the New York Heart Association at all
      assessments. Ventilatory anaerobic threshold, however, was significantly lower
      than normal. It averaged 77.9% +/- 13.7 of the normal mean value at the initial
      evaluation, and remained stable when re-evaluated later (76.2 +/- 13.7%). At the
      initial study, the increase in oxygen uptake during graded exercise was below the
      95% confidence limit in 6 of the patients, and was below this level in 10
      patients at re-assessment. The subnormal values for oxygen uptake during
      submaximal exercise were associated with moderate to severe haemodynamic
      dysfunction. At echocardiography, 15 of 17 patients studied twice had mild to
      moderate right ventricular dilation and tricuspidregurgiation, which remained
      virtually the same at reasssesment. A stable sinus rhythm was initially present
      in 17 patients, and persisted in 15 patients during follow-up. CONCLUSION: At
      medium term follow-up, cardiorespiratory exercise performance remains stable in
      patients after atrial switch repair. Serial exercise testing appears useful,
      because in individual patients in the present study, a decreasing exercise
      tolerance correlated with development of haemodynamic sequels.

PMID- 11233393
TI  - Levels of lipoprotein (a) in pulmonary arterial hypertension.
AB  - We compared the levels of lipoprotein (a) in 48 Caucasian patients with pulmonary
      arterial hypertension, comprising 32 females and 16 males, aged 28.0 +/- 12.0
      years, with a range from 4 through 52 years, with 48 normal Caucasian subjects
      matched for age and sex. Pulmonary hypertension was secondary in 41 patients with
      Eisenmenger's syndrome, these comprising 27 females and 14 males aged 27.0 +/-
      12.0 years, with a range from 4 through 51 years, and primary in the other 7
      patients, 5 females and 2 males, whose age was 30.0 +/- 14.0 years, with a range
      from 9 through 52 years. Lipoprotein (a) was measured using an
      immunoprecipitation and turbidimetric assay after a 12 hour fast. Levels of the
      protein, expressed as the median (% 25; % 75), were higher in those with
      Eisenmenger's syndrome than in normal controls (p=0.003). In addition, there was
      a greater prevalence of levels of lipoprotein greater than 30.0 mg/dl in those
      with secondary pulmonary arterial hypertension patients than in our normal
      population (p = 0.03). We have found no differences, however, in the levels of
      lipoprotein(a) in those who had primary pulmonary arterial hypertension when
      compared with their matched controls, albeit that the number of patients studied
      was small. We conclude that increased levels of lipoprotein (a) may be secondary
      to pulmonary arterial hypertension as a marker of tissue damage or may be
      genetically determined. In either way, the increase in lipoprotein (a) could be
      an additional factor predisposing to the vascular alterations known to occur in
      this disease.

PMID- 11233394
TI  - Improved early results with cavopulmonary connections.
AB  - BACKGROUND: We describe the recent results in a large cohort of patients with
      functionally single ventricle who underwent various modifications of
      cavopulmonary connections. METHODS: Using the database at our institution, we
      identified all children who underwent cavopulmonary connection operations between
      June 1995 and June 1997. Demographic data, surgical history, and perioperative
      course were reviewed. RESULTS: We performed 130 consecutive operations in 113
      patients. The procedures included superior cavopulmonary connections in the form
      of the HemiFontan procedure in 45 instances, and bidirectional Glenn procedures
      in 11, and bilateral superior cavopulmonary connections in 7. The median age of
      these patients was 7.0 months. We completed Fontan operations using a fenestrated
      lateral tunnel on 47 occasions, and using an extracardiac conduit 9 times, 5 of
      which were fenestrated. A lateral tunnel without fenestration was constructed in
      one patient. The median age for these procedures was 19.5 months. In the
      remaining 10 instances, we revised Fontan procedures at a median age of 8 years.
      Diagnoses included hypoplastic left heart syndrome in 43 patients, double outlet
      right ventricle in 22, heterotaxy in 13, tricuspid atresia in 13, and a
      miscellaneous group accounting for the other 22. One death (0.7%) occurred within
      30 days of surgery. Clinical seizures occurred in 7 children (5.3%), 6 had no
      residual neurologic deficits. Atrial pacing was needed in 14 children (10.7%)
      because of transient junctional rhythm, and 2 received treatment for
      supraventricular tachycardia. Pleural effusions were diagnosed radiographically
      after 31 of 130 (24%) procedures. Diuretic therapy resolved the effusion in 21 of
      these, with only 6 children requiring thoracostomy catheter drainage, and 4
      undergoing thoracentesis alone. The median length of stay on the intensive care
      unit was 2 days, with a range from 1 to 30 days, and median stay in hospital was
      6 days, with a range from 3 to 58 days. CONCLUSION: Mortality and perioperative
      morbidity after cavopulmonary connections have decreased dramatically in the
      current era. The long-term results of staged reconstruction for functionally
      single ventricle, nonetheless, await ongoing study.

PMID- 11233395
TI  - Balloon dilation for aortic recoarctation: morphology at the site of dilation and
      long-term efficacy.
AB  - OBJECTIVES: We undertook this study to assess the immediate and long-term outcome
      of balloon angioplasty performed for recurrent or residual coarctation of the
      aorta, and to assess the changes in the vessel wall caused by this procedure.
      METHODS: Clinical, echocardiographic, angiographic and hemodynamic data from 71
      patients who underwent balloon angioplasty for recoarctation between January 1987
      and January 1998 were analysed retrospectively. RESULTS: Angioplasty was
      performed after a median of 82.6 months (range 1.4 mo-20.9 y, mean 88.5 mo)
      following surgery for coarctation. Mean systolic pressure gradients were reduced
      from 27 +/- 15 mmHg to 11 +/- 11 mmHg after angioplasty (p < 0.0001). The mean
      diameter at the site of recoarctation increased from 5.5 +/- 2.5 to 7.5 +/- 2.7
      mm (p < 0.0001). Outpouchings of contrast agents, indicating the disruption of
      the inner layers of the vessel wall, were defined as extravasations. They were
      observed in one-quarter of the angiograms performed immediately after the
      intervention. Immediate success of angioplasty was achieved in 71%, and persisted
      in 69% of patients during long-term follow up. The main determinant for immediate
      success was the age at the time of the procedure (p < 0.05), while the main
      determinant for long-term success was the increase achieved in diameter.
      Extravasations did not progress to aneurysms, neither acutely nor during
      echocardiographic follow-up studies. For further follow-up, more sensitive
      imaging techniques will be necessary to delineate the morphology of the site of
      extravasation observed immediately after angioplasty.

PMID- 11233396
TI  - Cytokines and pediatric open heart surgery with cardiopulmonary bypass.
AB  - It is well known that, subsequent to cardiopulmonary bypass, and particularly in
      children, an inflammatory response within the body can often result in a
      characteristic syndrome. Recently, it has been suggested that this phenomenon is
      due to a systemic inflammatory response, with significant involvement of
      cytokines. With this in mind, we investigated the behavior of tumour necrosis
      factor-alpha and interleukin-6 during the operative and in the immediate
      postoperative period in a group of children submitted to open heart surgery. We
      investigated any possible relation between the levels of these cytokines in the
      serum and the length of cardiopulmonary bypass, with the serum levels of lactate,
      and with the extent of use of inotropic drugs in postoperative period. The
      cytokines were measured in samples withdrawn after induction of anesthesia, after
      10 minutes of cardiopulmonary bypass, after re-establishment of circulation, and
      then 2 and 24 hours after the end of cardiopulmonary bypass. The levels of tumour
      necrosis factor-alpha and interleukin-6 increased between the beginning and at
      two hours of the end of cardiopulmonary bypass. There was no correlation between
      the levels of these cytokines in the serum and the length of cardiopulmonary
      bypass, although there was a positive relation between levels of interleukin-6
      and lactate in samples withdrawn at two hours of the end of bypass, and the
      measured levels of the cytokines correlated with the extent of inotropic drugs
      employed in the postoperative period.

PMID- 11233397
TI  - The risk of having additional obstructive lesions in neonatal coarctation of the
      aorta.
AB  - Infants with coarctation of the aorta may have obstructions at other sites within
      the left heart which are not always apparent on the initial echocardiogram. The
      magnitude of the risk of having the additional obstructions is not well
      described, with few reliable quantitative criterions for identifying patients at
      the highest risk. We determined the frequency of additional, late appearing,
      stenotic lesions within the left heart, and the predictive morphologic features
      on the initial cross-sectional echocardiogram. We identified all patients with
      coarctation of the aorta diagnosed by 3 months of age, excluding those with
      complex cardiac disease or definite additional stenotic lesions at presentation,
      leaving 101 patients for study. At follow-up, 31 stenotic lesions were diagnosed
      in 23 patients, 15 of whom had at least 1 intervention. Mitral stenosis was
      diagnosed in 11 patients, aortic stenosis in 10, subaortic stenosis in 8, and
      supravalvar aortic stenosis in 2. The probability for freedom from obstructive
      lesions was 81% at 1 year, 74% at 3 years, and 70% at 5 years. Echocardiographic
      predictors of mitral stenosis included smaller mitral valvar annuluses, presence
      of a mean transmitral gradient between 2.5 and 5.0 mmHg, and elongation of the
      area of intervalvar fibrous continuity. Predictors of aortic stenosis were
      smaller mitral valvar annuluses, an initial aortic valvar gradient between 15 and
      20 mmHg, and obliteration of the commissure between the right and non-coronary
      leaflets of the aortic valve. Predictors of subaortic stenosis were smaller
      mitral valvar annuluses and elongation of the area of intervalvar fibrous
      continuity. Patients with Z-scores for the diameter of the mitral valve of less
      than -1 were at the highest risk for manifesting obstructive lesions at any
      level. Associated stenoses in the left heart are common in the setting of aortic
      coarctation. When Doppler data is equivocal, features of the cross-sectional
      echocardiogram can identify the sub-group of infants at increased risk.

PMID- 11233398
TI  - Outcomes of transcatheter balloon angioplasty of obstruction in the neo-aortic
      arch after the Norwood operation.
AB  - Obstruction of the reconstructed aortic arch, or the neoaortic arch, is now known
      to be an important factor increasing mortality after the Norwood operation for
      hypoplastic left heart syndrome. Transcatheter balloon angioplasty has been shown
      to provide effective relief of both native aortic coarctation and obstructions of
      the aortic arch occurring subsequent to therapeutic intervention. We sought to
      determine the outcomes of balloon angioplasty used as an initial treatment for
      obstruction of the neoaortic arch occurring after the Norwood operation. We
      gathered the characteristics of 58 patients with such obstruction from 8
      institutions, noting procedural factors and outcomes of initial balloon dilation.
      Obstruction occurred at a median interval of 4 months, with a range from 1.5
      months to 6.3 years, after a Norwood operation. Ventricular dysfunction was
      present before dilation in 13 patients. Mean peak to peak systolic pressure
      gradients were acutely reduced from 31+/-20 mm Hg to 6+/-9 mmHg (p<0.001), with
      outcome subjectively judged to be successful in 89%. Three patients with pre
      existing ventricular dysfunction died within 48 hours of dilation. There were 10
      additional deaths during the period of follow-up, with Kaplan Meier estimates of
      survival after intervention of 87% at 1 month, 77% at 12 months, and 72% after 15
      months. In addition, 9 patients required re-intervention during the period of
      follow-up, with Kaplan Meier estimates of freedom from re-intervention after
      dilation of 87% at 6 months, 78% at 12 months and 74% after 18 months. Although
      transcatheter dilation of neoaortic arch obstructions after Norwood operation is
      successful, there is a high risk of re-intervention and ongoing mortality in this
      subgroup of patients. Close follow-up is recommended.

PMID- 11233399
TI  - Coagulation profile, hepatic function, and hemodynamics following Fontan-type
      operations.
AB  - We analyzed retrospectively the relationship between coagulation profile, and
      either hepatic function or hemodynamics, in patients who had undergone a Fontan
      type procedure, comparing them, first, with a control group of 12 patients
      without significant hemodynamic abnormality, and, second, with a group of 14
      patients who had not undergone a Fontan procedure, but whose mean right atrial
      pressure exceeded 8 mmHg. Follow-up catheterization had been performed in all 30
      patients submitted to the Fontan-type operation. Prothrombin time, and factor
      XIII, were significantly lower in those who had undergone the Fontan procedure
      than in the other groups. Those submitted to the Fontan operation also had lower
      levels of protein C than controls, and their levels of plasminogen were lower
      than the patients with high right atrial pressure. Both aspartate
      aminotransferase and alanine aminotransferase were higher in those undergoing the
      Fontan procedure than in the other groups, while gamma-glutamyltranspeptidase in
      these patients was higher than in the control group. Mean right atrial pressure
      was highest in those undergoing the Fontan procedure, while cardiac index was
      lowest. Prothrombin time was correlated to some extent with aspartate
      aminotransferase, mean right atrial pressure, and cardiac index. Protein C
      correlated with both aspartate aminotransferase and mean right atrial pressure,
      while factor XIII correlated with alanine aminotransferase, mean right atrial
      pressure, and cardiac index. Aspartate aminotransferase, alanine
      aminotransferase, and gamma-glutamyltranspeptidase, parameters of hepatic
      function, correlated significantly with mean right atrial pressure. In those who
      had undergone the Fontan procedure, decreased synthesis of pro-and anti-coagulant
      factors is a risk factor for both thrombosis and bleeding. Abnormal hemodynamics,
      in the absence of a right sided pumping chamber, may predispose to subclinical
      hepatic dysfunction, leading to selective disturbances of protein synthesis.

PMID- 11233400
TI  - Postpericardiotomy syndrome: no evidence for a viral etiology.
AB  - BACKGROUND: Postpericardiotomy syndrome has been considered a disorder induced by
      viral infection. This conclusion is based on serologic criterions, but these may
      be unreliable following either cardiopulmonary bypass or transfusion therapy.
      Previous studies have not verified the proposed etiology either by isolation of
      viruses, or by detection of their genome. We sought, therefore, to clarify the
      role, if any, of viruses in this syndrome. METHODS AND RESULTS: We studied
      prospectively 149 children aged from 6 months to 16 years who were undergoing
      open heart surgery. Blood samples were collected from all prior to operation, and
      again 7 to 10 days post-operatively, and 47 were sampled at the time of
      development of symptoms of pericardial involvement. Serums were analyzed for the
      presence of IgM and IgG antibodies to cytomegalovirus, herpes simplex virus, and
      Epstein-Barr virus. The polymerase chain reaction was used for amplification when
      assessing the genome of the enteroviruses. Cultures for viruses were established
      on samples of stool, urine, and throat swabs collected 7 days post-operatively,
      and at the time of postpericardial symptoms. Pericardial fluid obtained from 5
      patients with the syndrome was cultured for viruses, and tested for enterovirus
      genome. On the basis of clinical and echocardiographic findings, 34 children were
      determined to have definite evidence of the syndrome, 13 were considered to have
      possible evidence, and the results from these patients were compared to those
      from patients with no pericardial symptoms, the latter being matched for age and
      transfusion status. We isolated viruses from one or more sites in five patients
      with definite evidence (16%), from one (9%) of those with possible evidence, and
      from seven (19%) of the controls. All serums and pericardial samples were
      negative for enterovirus genome. IgM antibodies were found in only 5 patients,
      three with symptoms of pericardial involvement and two without. Rates of
      seroconversion to IgG for the viruses were lower in the patients with symptoms of
      pericardial involvement compared to controls, but were strongly influenced by
      transfusion status. CONCLUSION: Our study has provided no evidence to support a
      viral etiology for the postpericardiotomy syndrome.

PMID- 11233401
TI  - Unusual totally anomalous pulmonary venous connection in right isomerism and
      functionally univentricular heart.
AB  - We report a rare variation in the pattern of totally anomalous pulmonary venous
      connection in that two vertical veins drained into the left brachiocephalic vein
      from a common pulmonary venous confluence. The child had associated right
      isomerism and functionally univentricular heart. Awareness of this possibility
      may avoid a reoperation or even death.

PMID- 11233402
TI  - Left ventricular function before and after repair of an anomalous left coronary
      artery arising from the pulmonary trunk.
AB  - We report an infant with an abnormal left coronary artery arising from the
      pulmonary trunk in whom, subsequent to surgical repair, sequential improvements
      in regional left and right systolic and diastolic myocardial function were
      quantified by the new ultrasound-based method of regional strain and strain rate
      imaging. The regional radial and longitudinal myocardial function of the left
      ventricle was homogeneously reduced prior to repair, while the time course of
      their recovery differed subsequent to repair. We discuss the concepts and
      advantages behind this quantitative approach to monitoring regional myocardial
      function in children.

PMID- 11233403
TI  - Successful occlusion of a coronary arteriovenous fistula using an Amplatzer duct
      occluder.
AB  - In an 11-year old boy with a large coronary arteriovenous fistula between the
      left coronary artery and the right atrium, we achieved successful closure using a
      10-8 Amplatzer Duct Occluder introduced from the right internal jugular vein.
      Angiography 6 weeks later showed complete occlusion of the fistula, with normal
      opacification of the left coronary arterial system. This technique may be used as
      an alternative to coils and surgery in selected patients.

PMID- 11233404
TI  - Coarctation co-existing with tetralogy of Fallot and pulmonary atresia.
AB  - We describe the finding of unsuspected aortic coarctation, discovered by
      catheterisation at 4 months, in a neonate first daignosed on the fourth day of
      life as having tetralogy of Fallot with pulmonary atresia and major aorto-to
      pulmonary collateral arteries. This previously unreported combination contravenes
      the established theory of patterns of flow during fetal life, and presented
      difficult issues in clinical management.

PMID- 11233405
TI  - Replacement of the mitral valve in an infant with group B streptococcal
      endocarditis.
AB  - Endocarditis due to group B streptococcus is very rare in infants, and may be
      associated with significant morbidity and mortality. Review of the literature
      reveals only a single reported case of an infant with this type of streptococcal
      endocarditis involving the mitral valve. This infant had underlying congenital
      heart disease, and died shortly after catheterization. We now report group B
      streptococcal endocarditis occurring in an infant with a structurally normal
      heart who was treated successfully by replacement of the mitral valve.

PMID- 11233406
TI  - Images in congenital heart disease. Ruptured aneurysm of the sinus of valsalva.

PMID- 11233407
TI  - The spectrum of fetal cardiac malformations.
AB  - Increasingly, paediatric cardiologists are called upon to diagnose cardiac
      malformations prenatally. In the main, the types of malformation seen during
      fetal life will be similar to those documented postnatally, but the frequency
      with which they are encountered, as well as the views that can be used for
      diagnosis, will be different. This review aims to describe the anatomic spectrum
      of malformations seen in 917 fetal hearts examined consecutively following
      prenatal diagnosis. The distribution of anomalies is illustrated in terms of a
      simple sweep through the fetal thorax passing from the four-chamber plane to the
      outflow tracts, and then to more cranial views of the mediastinum. Two-thirds of
      the anomalies described would have been detectable in the four-chamber plane.
      Some, such as tricuspid valvar abnormalities, will alter the normal appearances
      of the four-chambers dramatically. In terms of the overall spectrum, however,
      such obvious abnormalities only form a minor part of the total number. Others,
      such as atrioventricular septal defect, will often require closer inspection of
      intracardiac anatomy, but will make up a large proportion of the entire cohort.
      Up to one third of the anomalies in the series would have required views more
      cranial to the four-chamber plane of section. In these, it would have been
      necessary to examine the nature of the left ventricular outflow tract, the
      crossing of the two outflows, or else the arterial arches in order to secure
      detection. In the fetus, these and other planes must be considered by the
      echocardiographer in order completely to detect and document the entire spectrum
      of cardiac abnormalities likely to be encountered.

PMID- 11233408
TI  - Single-particle electron cryo-microscopy: towards atomic resolution.

PMID- 11233409
TI  - NMR structures of biomolecules using field oriented media and residual dipolar
      couplings.

PMID- 11233410
TI  - Microgravity increases the affinity of lipoxygenases for free fatty acids.

PMID- 11233411
TI  - Ecology. A roaring debate over ocean noise.

PMID- 11233412
TI  - Ecology. New sensors provide a chance to listen to the leviathan.

PMID- 11233413
TI  - American Astronomical Society. Celestial zoo gains some exotic specimens.

PMID- 11233415
TI  - American Geophysical Union. Predicting Icelandic fire and shakes.

PMID- 11233416
TI  - American Geophysical Union. Atmosphere's power grid exposed.

PMID- 11233414
TI  - Cancer research. Anti-inflammatories inhibit cancer growth--but how?

PMID- 11233417
TI  - American Geophysical Union. Earth's breathing lessons.

PMID- 11233419
TI  - The human genome.

PMID- 11233418
TI  - Australia. Engineered mouse virus spurs bioweapon fears.

PMID- 11233420
TI  - The human genome.

PMID- 11233421
TI  - The human genome. Comparison shopping.

PMID- 11233422
TI  - Watching genes build a body.

PMID- 11233423
TI  - The human genome. Objection #1: big biology is bad biology.

PMID- 11233424
TI  - The human genome. Controversial from the start.

PMID- 11233425
TI  - Finding the talismans that protect against infection.

PMID- 11233426
TI  - The human genome. Objection #2: why sequence the junk?

PMID- 11233427
TI  - Nailing down cancer culprits.

PMID- 11233428
TI  - The human genome. Objection #3: impossible to do.

PMID- 11233430
TI  - Brain calls dibs on many genes.

PMID- 11233429
TI  - A parakeet genome project?

PMID- 11233431
TI  - The human genome. Sharing the glory, not the credit.

PMID- 11233433
TI  - Bermuda rules: community spirit, with teeth.

PMID- 11233432
TI  - Celera and Science spell out data access provisions.

PMID- 11233434
TI  - Genomania meets the bottom line.

PMID- 11233435
TI  - Will a smaller genome complicate the patent chase?

PMID- 11233436
TI  - A history of the Human Genome Project.

PMID- 11233438
TI  - A genome glossary.

PMID- 11233437
TI  - The Human Genome Project. In their own words.

PMID- 11233439
TI  - Can data banks tally profits?

PMID- 11233440
TI  - What's next for the genome centers?

PMID- 11233441
TI  - Hunting for collaborators of killer toxins.

PMID- 11233442
TI  - The human genome. Unsung heroes.

PMID- 11233443
TI  - The human genome.   Science genome map.

PMID- 11233444
TI  - Genomics and society.   The human genome and our view of ourselves.

PMID- 11233445
TI  - Proteomics.  Proteomics in genomeland.

PMID- 11233446
TI  - Genomics and medicine.  Dissecting human disease in the postgenomic era.

PMID- 11233447
TI  - Genomics and behavior.  Toward behavioral genomics.

PMID- 11233448
TI  - Policy issues.  Political issues in the genome era.

PMID- 11233450
TI  - Gene number.  What if there are only 30,000 human genes?

PMID- 11233451
TI  - Sequence interpretation.  Making sense of the sequence.

PMID- 11233449
TI  - Sequence interpretation.  Functional annotation of mouse genome sequences.

PMID- 11233452
TI  - Computational biology.  Bioinformatics--trying to swim in a sea of data.

PMID- 11233453
TI  - Tech.Sight. Worth its weight in gold.

PMID- 11233454
TI  - Effectiveness of antidepressant pharmacotherapy: the impact of medication
      compliance and patient education.
AB  - This study was designed to investigate the impact of a time-phased patient
      education program (RHYTHMS) on medication compliance and treatment outcomes of
      primary care patients diagnosed with major depression and started on
      antidepressant pharmacotherapy. Two hundred forty-six depressed patients,
      diagnosed and treated at one of three outpatient clinics affiliated with the
      Kaiser-Permanente Northwest Region (KPNW) healthcare system, were randomly
      assigned to either receive or not receive (usual care) the educational materials
      by mail. Depression severity and functional impairment affecting patients'
      quality of life were assessed at baseline and 4, 12, and 30 weeks later. Self
      reported impressions of improvement and patient satisfaction with treatment were
      also assessed at follow-up. Clinical assessment data were obtained using an
      interactive voice response (IVR) system. Study subjects were compensated $5, $10,
      $15, and $25 for completing each assessment (Baseline to Week 30, respectively).
      Upon study completion, prescription fill data of the subjects were extracted from
      the KPNW Pharmacy System for analysis of medication compliance. Most of the study
      subjects (63.5%) responded to the pharmacotherapy treatment by study end-point.
      Few statistically significant differences in either treatment outcomes or
      duration of medication compliance were found between the treatment groups, and
      significant differences found were of fairly small magnitude. Patients not
      receiving the educational materials initially exhibited a more positive response
      to treatment (Week 4), but this difference did not persist at later follow-ups
      and was associated with significantly higher relapse rates. A strong time-dose
      relationship was evident between the duration of the initial treatment episode
      and treatment outcomes at follow-up, but randomized treatment assignment did not
      influence the duration of initial medication compliance. Educational programs
      designed to encourage depressed patients to obtain adequate pharmacotherapy
      likely provide medical benefits. Such benefits appear to be relatively subtle and
      methodological differences between studies contribute to inconsistent conclusions
      concerning observed benefits. The intent of providing time-phased educational
      materials to patients is to maximize the relevance of such information by
      synchronizing it with typical recovery processes and issues. This study suggests
      that additional efforts at engaging patients earlier after the initiation of
      treatment might be of most benefit.

PMID- 11233455
TI  - Differential subtyping of depression.
AB  - We studied a group of patients with depression divided into subtypes of non
      chronic major depression, chronic major depression, and pure dysthymia. The
      purpose of this study was to determine if clinical and family history factors
      separated these types of depression. We reviewed records from semi-structured
      clinical interviews and abstracted data regarding factors that might
      differentiate these three depressive subtypes. In general we found what might be
      predicted from the definitions of dysthymia versus major depression, that is,
      ratings for severity of depression were lower for dysthymic patients as compared
      to patients with non-chronic or chronic major depression. We also found lower
      ratings for social functioning (GASF) for dysthymic patients as compared to the
      other depressive subtypes. Our study does not provide data to sufficiently
      separate these three subtypes. However, in the course of reviewing the literature
      on this topic, very few studies have separated patients into these distinct
      depressive subtypes. Further studies are needed to indicate if these subtypes can
      be meaningfully separated.

PMID- 11233456
TI  - Effect of concurrent anxiety on response to sertraline and imipramine in patients
      with chronic depression.
AB  - Anxiety commonly complicates the clinical presentation of depression and has been
      associated with poorer long-term outcome, but little information is available on
      the clinical correlates, and comparative effect on treatment response, of
      subsyndromic or secondary anxiety. Patients diagnosed with chronic major or
      double depression were randomized to 12 weeks of double-blind treatment with
      either sertraline or imipramine in a 2:1 ratio. A high anxiety subgroup was
      operationally defined by a HAM-D anxiety/somatization factor score > or = 7. The
      effect of study treatment was measured utilizing the HAM-D, CGI, HAM-D
      anxiety/somatization factor, as well as a quality of life measure (Q-LES-Q) and a
      measure of psychosocial functioning (the MOS-SF-36). Two hundred nine patients
      were treated with imipramine and 426 patients were treated with sertraline.
      Thirty-six percent of the total met criteria for the high anxiety subgroup.
      According to Kaplan-Meier probability estimates, patients with significant
      concurrent anxiety symptoms were more likely to respond by 12 weeks (66.4%) than
      those without significant anxiety symptoms (54.2%). There was no significant
      difference in response rates for sertraline vs. imipramine. Both drugs were
      effective at treating high baseline levels of anxiety, with 60% of sertraline
      patients and 58% of imipramine patients having 50% or greater reduction from
      baseline in HAM-D anxiety/somatization factor scores, and only 4.6% and 9.9%,
      respectively, reporting treatment-emergent worsening in anxiety at study
      endpoint. Despite the chronicity of depressive illness, acute treatment with both
      sertraline and imipramine significantly improved psychosocial and quality of life
      measures. High baseline levels of anxiety did not reduce overall antidepressant
      response but did somewhat delay the onset of response to sertraline or imipramine
      in patients with chronic depression.

PMID- 11233457
TI  - Depressive symptoms in African-American type 1 diabetics.
AB  - This study examined depressive symptoms and their correlates in African-American
      patients with type 1 diabetes. Five-hundred eighty-one diabetics participated in
      a study on risk factors for retinopathy in African-Americans with type 1
      diabetes. Evaluations included structured interview, ocular examination, blood
      test, and completion of the Beck Depression Inventory (BDI). Among the 581
      diabetic patients, 159 (26.9%) had a BDI score > 14. Significantly more of these
      patients were unemployed, had less education, lower socio-economic status, and
      less personal and family income than those who had a BDI < or = 14. Also,
      significantly more patients with a BDI score > 14 had proliferative retinopathy
      and were receiving disability payments. In the multiple logistic regression, two
      factors that significantly and independently associated with the BDI score > 14
      were unemployment or not working due to disability. Both socio-economic and
      diabetic variables are associated with depressive symptoms among African-American
      patients with type 1 diabetes.

PMID- 11233458
TI  - CES-D depression scores are correlated with frontal EEG alpha asymmetry.
AB  - In order to evaluate the relationship between frontal EEG asymmetry and
      depressive symptomology, the Center for Epidemiological Studies Depression scale
      [CES-D; Radloff, 1977] was given to 163 women, and their EEG was recorded from
      the mid frontal (F3 and F4) and parietal (P3 and P4) regions during a 3 min
      baseline recording. As expected from previous research on depression, CES-D
      scores were negatively correlated with frontal EEG alpha asymmetry scores and
      positively correlated with left frontal EEG alpha power. Analyses of variance
      further revealed that mothers scoring above the cut-off for depression (CES-D >
      or = 16) had significantly lower frontal EEG asymmetry scores than mothers with 0
      2 and 3-12 CES-D scores but not lower scores than mothers with 13-15 CES-D
      scores.

PMID- 11233459
TI  - Paroxetine versus nortriptyline in the continuation and maintenance treatment of
      depression in the elderly.
AB  - Elderly depressed patients are vulnerable to recurrence of depression and benefit
      from long-term antidepressant therapy. Physicians increasingly use selective
      serotonin re-uptake inhibitors (SSRIs) as maintenance therapy, although in the
      absence of data showing that SSRIs are as efficacious as tricyclic
      antidepressants (TCAs) in the prevention of depression relapse and recurrence.
      Our objective was to evaluate, in an open trial, the efficacy of paroxetine
      versus nortriptyline for preventing recurrence of depression in the elderly.
      Elderly patients with major depression were randomly assigned in a double-blinded
      fashion to receive either paroxetine or nortriptyline for the acute treatment of
      depression. Patients who did not respond or tolerate their assigned medications
      were crossed over openly to the comparator agent. Patients whose depression
      remitted continued antidepressant medication (paroxetine n = 38; nortriptyline n
      = 21) during an open 18-month follow-up study. We examined the rates of and times
      to relapse and to termination of treatment for any reason. Paroxetine (PX) and
      nortriptyline (NT) patients had similar rates of relapse (16% vs. 10%,
      respectively) and time to relapse (60.3 weeks vs. 58.8 weeks, respectively) over
      18 months. A lower burden of residual depressive symptoms and side effects during
      continuation and maintenance treatment was evident in nortriptyline-treated
      patients. Paroxetine and nortriptyline demonstrated similar efficacy in relapse
      and recurrence prevention in elderly depressed patients over an 18-month period.

PMID- 11233460
TI  - Early-onset versus late-onset bipolar II chronic depression.
AB  - Age at onset is an important dimension in the classification of mood disorders.
      Recent findings on early-onset (EO) versus late-onset (LO) unipolar chronic
      depressions support this subtyping. The aim of the present study was to determine
      clinical differences between EO and LO bipolar II chronic depression and to
      support this subtyping also in bipolar II. Eighty-seven consecutive bipolar II
      chronic depression outpatients were interviewed with the Structured Clinical
      Interview for DSM-IV, the Montgomery Asberg Depression Rating Scale, and the
      Global Assessment of Functioning scale. EO cut-offs were 21 and 23 years of age.
      Variables, studied with linear and logistic regression, were age, gender, age at
      onset, illness duration, recurrences, atypical, melancholic, and psychotic
      features, axis I comorbidity, and severity. Lower age at onset was significantly
      associated with lower age, longer illness duration, less psychosis, less
      severity, more atypical features, and more axis I comorbidity. Results support
      the subtyping of bipolar II chronic depression in EO and LO on the basis of
      different clinical features.

PMID- 11233461
TI  - Nortriptyline toxicity secondary to interaction with bupropion sustained-release.

PMID- 11233462
TI  - [Silent victims of street traffic].

PMID- 11233463
TI  - [Pacemaker dysfunction in the clinical practice].
AB  - Lead dysfunction is still the predominant cause of pacemaker dysfunction. Beyond
      lead dysfunction clinicians might encounter problems resulting from the surgical
      procedure of pacemaker implantation, from specific programmable pacemaker
      functions (e.g. undersensing of premature ventricular complexes when autosensing
      is activated) and from interference with electromagnetic fields. Electromagnetic
      interference between pacemakers and mobile phones has been demonstrated both in
      vitro and in vivo, but in daily life pacemaker patients can readily use mobile
      phones when certain security measures are taken into account. Electromagnetic
      interference between anti-theft devices and pacemakers can arise from situations
      where the pacemaker is in close proximity to the anti-theft device, but in daily
      life these interferences are rare. The electromagnetic fields generated during
      magnetic resonance imaging (MRI) are considerably stronger than those generated
      by mobile phones or anti-theft devices, therefore permanent pacemakers are still
      considered a contraindication for MRI, although several case reports have
      recently been published that reported on uneventful MRI procedures in pacemaker
      patients. The present review summarizes the current knowledge on the most
      frequent pacemaker dysfunctions and electromagnetic interferences that might be
      relevant in clinical practice.

PMID- 11233465
TI  - A prospective randomized trial comparing the cuffed oropharyngeal airway (COPA)
      with the laryngeal mask for elective minor surgery in female patients.
AB  - OBJECTIVE: The cuffed oropharyngeal airway (COPA), a modified Guedel-type airway
      with a cuff at the distal end, has recently been introduced into anesthetic
      practice. The aim of this study was to compare the COPA with the well established
      laryngeal mask airway (LMA). Special consideration was granted to the difficult
      airway. PATIENTS AND METHODS: Two hundred and fifty-two women of ASA class I or
      II undergoing elective gynecological or breast surgery under general anesthesia
      were randomly assigned to either cuffed oropharyngeal or laryngeal mask airway
      management. Insertion and removal of the device, airway maintenance throughout
      the procedure, and postoperative course and complications were assessed. RESULTS:
      A patent airway was obtained with either device in all patients. Global first
      time success rates for insertion were similar in the two study groups. Initial
      failure of correct placement occurred more frequently in the COPA as compared to
      the LMA group if the interincisor gap was < 5 cm and mandibular protrusion
      impossible (p < 0.01). Neither thyromental distance nor Mallampati scores nor
      body mass index (BMI) were of relevance for insertion success. The incidence of
      postoperative complaints and of mucosal injuries was significantly higher with
      the LMA. CONCLUSION: On the whole, high overall success and low complication
      rates render COPA and LMA equally suitable for routine anesthetic airway
      management.

PMID- 11233464
TI  - Epidemiology of sudden infant death syndrome (SIDS) in the Tyrol before and after
      an intervention campaign.
AB  - OBJECTIVE: We investigated the epidemiology of sudden infant death syndrome
      (SIDS) in the Tyrol before and after an intervention campaign. PATIENTS AND
      METHODS: Descriptive characteristics and risk factors of SIDS before the campaign
      were assessed in a retrospective case-control study (1984 to 1994). In April 1994
      a country-wide information campaign on modifiable risk behaviours was initiated.
      Thereafter we prospectively collected data on child care practices four to six
      weeks after birth for all infants born in the Tyrol (participation rate 72%; n =
      28,361) and evaluated new SIDS cases (1994 to 1998). For this purpose two
      questionnaires were used, one with 96 items for the evaluation of all SIDS cases
      and assessment of child care practices before 1994, and the other with 24 items
      for prospective data collection. RESULTS: The incidence of SIDS decreased from
      1.83 (mean incidence, 1984-1994) to 0.4/1000 live births immediately after the
      campaign and remained low until 1998. The frequency of maternal smoking during
      pregnancy declined (22.9% vs. 14.5%, p < 0.01), as did the prevalence of the
      prone sleeping position (53.7% vs. 5.4%, p < 0.001) and of non-breastfeeding
      (21.3% vs. 6.7%, p < 0.001). All these variables were prominent risk factors for
      SIDS before the campaign and remained significant thereafter. On account of the
      markedly reduced prevalence of the prone sleeping position, smoking became the
      most common SIDS risk factor. The prevalence of sleeping on the side
      significantly increased (5.1% vs. 36.4%, p < 0.001) and the social status of
      mothers of SIDS infants tended to be lower than that before the campaign. The
      clear winter preponderance of SIDS which was evident before the campaign
      disappeared, or was even reversed. CONCLUSIONS: Our study documents the long-term
      efficacy of a low-cost intervention campaign by way of health education. Further
      efforts must be directed toward lower social classes, thereby focusing on
      maternal smoking and avoidance of the side sleeping position.

PMID- 11233466
TI  - Borrelia infection as a cause of carditis (a long-term study).
AB  - BACKGROUND: Although the frequency of Lyme carditis is not high, it is one of the
      most challenging conditions in terms of diagnosis. No long-term studies that
      would help expand our body of knowledge concerning the circumstances of its
      development and the natural course of this form of Lyme borreliosis (LB), the
      most widespread anthropozoonosis in Central Europe, have been reported to date.
      AIM: The authors sought to describe and assess the consequences of a less common
      form of Lyme carditis (LC). An assessment of the following aspects was made: a)
      the forms, natural history and sequelae of the less common clinical appearances
      of LC, b) the role of antibiotic therapy with reference to the late
      manifestations of LB. METHODS: Three patients were selected from a group of 60
      consecutive patients with demonstrated LC during a follow-up period from 1987 to
      2000. Patient no. 1 was being followed for myocarditis with frequent ventricular
      extrasystoles, patient no. 2 for pericarditis, and patient no. 3 for dilated
      cardiomyopathy as a late manifestation of LB. In addition to routine examination
      at entry, the patients were subjected to a standard 12-lead ECG, continuous 24
      hour Holter ECG monitoring, exercise testing (bicycle ergometry), investigations
      of antibodies using ELISA and Western blot, investigation of thyroid (T3, T4, TSH
      tests) and mineral levels. RESULTS: The study showed no significant correlation
      between the clinical course and levels of specific antibodies. It confirmed the
      concept that inadequate or no therapy with antibiotics in the initial stage of
      the disease has a significant effect on the development of late sequelae.
      CONCLUSION: Based on the long-term treatment of three patients with less common,
      yet clinically urgent findings, the authors conclude that even a relatively
      serious clinical course is associated with no major limitations for affected
      individuals after an interval of several years.

PMID- 11233467
TI  - Realising the potential benefit of screening. Comment on the outcomes of the
      first Austrian Screening Guidelines Consensus Conference.

PMID- 11233468
TI  - [Laterality of tinnitus: relationship to functional assymetries].
AB  - Tinnitus is a sensation of sound generated by the auditory system due to
      pathology, without any external acoustic or electrical stimulation. Clinical
      reports have indicated that tinnitus affects the left ear more frequently than
      the right one. Previous data suggest that the asymmetrical distribution of
      tinnitus is linked to handedness or other lateral signs, but no studies have
      heretofore examined lateral preferences in addressing this relationship. The
      literature concerning the laterality (localisation) of tinnitus is reviewed. The
      data confirm an asymmetrical distribution of tinnitus. Results of 7 studies
      (altogether 4634 patients) demonstrate that tinnitus occurs more often
      bilaterally (48.8%) than on the left side (28.0%) or the right (23.2%). There is
      no general predominance of the left ear. Handedness, eyedness, footedness,
      earedness and dichotic listening are examined in our own sample of 58 patients
      (23 men and 35 women) with acute, subacute or chronic tinnitus. A right sided
      preference was found for hand, foot, eye, ear preference and dichotic listening
      among 91%, 86%, 78%, 69% and 85% of the sample, respectively. Sixty per cent of
      the sample heard tinnitus only in the left ear, 21% only in the right ear and 19%
      in both ears. There is a higher correlation between localisation of tinnitus and
      dichotic listening than between other lateralities. Our investigation shows a
      significant relationship between localisation of tinnitus and laterality of
      dichotic listening, suggesting a possible link between tinnitus and hemisphere
      dominance. The result suggests a "functional" asymmetry of tinnitus.

PMID- 11233469
TI  - Patterns of non-conductive olfactory disorders in eastern Austria: a study of 120
      patients from the Department of Otorhinolaryngology at the University of Vienna.
AB  - BACKGROUND: About 1% of the population suffer from disorders of the chemosensory
      system. In the United States at least two million people have problems related to
      smell and taste. The sense of smell enables the individual to determine the
      flavour of food and beverages and is most important as a sophisticated warning
      system. For the present investigation, we collected data on the age pattern and
      causes of olfactory disorders in eastern Austria. METHODS: 120 patients with non
      conductive olfactory disorders were examined over a 9-month period starting from
      July 1998 at the outpatient clinic of the Ear Nose and Throat Department of the
      University of Vienna. Data concerning the underlying population taken from the
      1998 population census in Vienna were used for comparison, in order to gain a
      more representative estimation of the distribution of these disorders. The
      diagnosis was based on thorough history taking, physical examination, CT scan,
      and olfactory testing for sensitivity by means of so-called "sniffin' sticks".
      RESULTS: The patients' ages ranged from 16 to 86 years (mean, 54.5 years; 74
      females, 46 males). Those older than 50 years seem to have a higher risk of
      developing olfactory disorders. Only 15 of the female patients were pre
      menopausal. Olfactory disorders were most frequently caused by viral infections
      in the upper respiratory tract (n = 51). Fifteen patients reported head trauma as
      a cause of olfactory loss, and 45 causes were idiopathic. Most of those in whom
      the olfactory disorder had been in existence for less than 3 months were anosmic
      (84%), very few were hyposmic (16% of a total of 19 patients). In contrast, 38%
      (of a total of 29 patients) in whom the disease had been in existence for 3 and 6
      months were hyposmic. Parosmia was reported in 16 cases. Most parosmias appeared
      after viral infection (56%). Eight of the 120 patients reported dysgeusia.
      CONCLUSIONS: The present study is a first step towards an assessment of olfactory
      disorders in Austria. We found similar causes of non-conductive olfactory
      disorders as have been reported in the literature for other countries, namely
      upper respiratory infection leading to postviral olfactory disorders, and head
      trauma. With increasing age women seem to suffer more often from chemosensory
      dysfunction than men, which may be related to hormonal factors.

PMID- 11233470
TI  - High-dose versus low-dose rate brachytherapy in definitive radiotherapy of
      cervical cancer.
AB  - BACKGROUND: To retrospectively compare the clinical outcome in cervical cancer
      patients treated by external irradiation and intracavitary high-dose rate (HDR)
      brachytherapy with iridium 192 versus low-dose rate (LDR) brachytherapy with
      radium 226 or caesium 139. METHODS: 450 LDR patients were treated from 1982 to
      1986 and compared with 189 HDR patients treated from 1993 to 1999. Cobalt (CO) 60
      treatment was replaced in the HDR group by modern megavoltage photon radiotherapy
      (Linac 25 MV). Brachytherapy was given in either 2 or 3 LDR radium 226 implants
      for the earlier patient cohort, and 3-6 HDR iridium 192 implants for the latter
      cohort. The primary endpoint assessed was the 3-year overall survival. RESULTS:
      The median duration of follow-up was 70 months (range, 2-108 months) in the LDR
      group and 34 months (range, 4-69 months) in the HDR group. Actuarial overall 3
      year survival after conventional LDR brachytherapy was 51.3%, versus 58.2% after
      HDR brachytherapy. No difference in 3-year survivors was seen in the small groups
      of stage I (68.3% vs. 84.6%) and stage IV (23.1% vs. 37.5%) patients. In stage II
      and III and in the overall group there were statistically significantly more 3
      year survivors in the HDR group (58.1% vs. 78.9%, p < 0.001 in stage II; 37.3%
      vs. 53.8%, p < 0.01 in stage III; and 46.7% vs. 67.2%, p < 0.001 in the total
      group). Retrospectively assessed complication rates in the former LDR group were
      3.8% for irreversible side effects, and 13.3% for chronic radiation damage. In
      the HDR group the actuarial late complication rates for grades 3 and 4 were 2.9%
      for the bladder, 4.0% for the bowel, and 6.1% for the rectum. CONCLUSION: In our
      preliminary experience, HDR brachytherapy combined with external beam radiation
      produced similar and even better survival rates compared with the LDR series. HDR
      brachytherapy combined with external beam radiation is an efficient method for
      the treatment of cervical cancer and adverse side effects are comparable.

PMID- 11233471
TI  - Declining chloroquine resistance of Plasmodium falciparum in Lambarene, Gabon
      from 1992 to 1998.
AB  - Plasmodium falciparum malaria continues to threaten human populations in the
      tropics and travellers in endemic areas. Drug resistance of the parasite is a
      major problem in treating this devastating disease. In a prospective trial we
      investigated the in vitro sensitivity of Plasmodium falciparum to chloroquine,
      quinine and mefloquine in the Albert Schweitzer Hospital in Lambarene, Gabon
      every second year from 1992 to 1998. We used the standard WHO in vitro
      sensitivity assay. Parasite sensitivity to quinine and mefloquine remained stable
      over the years. However, parasite resistance to chloroquine decreased highly
      significantly with the change in local malaria treatment policy. In 1992, 100% of
      parasite isolates showed resistance to chloroquine, whereas in 1998 only 45% were
      found resistant.

PMID- 11233472
TI  - Serum calcium in thyroid disease.
AB  - Thyroid hormones are believed to influence calcium metabolism. In the present
      prospective study we investigated the influence of various thryroid diseases on
      serum calcium levels. In addition to screening for thyroid diseases we measured
      serum calcium concentrations (S-Ca) in individuals who came to our outpatient
      service for thyroid diseases from 1992 to 1998. 13,387 persons, among them 9017
      patients with thyroid diseases and 4370 persons without thyroid dysfunction, were
      studied. S-Ca was found to be higher in patients with hyperthyroidism (2.36 +/-
      0.11 mmol/L n = 1201, p < 0.05) than in those with subclinical hyperthyroidism
      (2.33 +/- 0.11 mmol/L, n = 494), with euthyroid goiter (2.32 +/- 0.10 mmol/l, n =
      5599), with hypothyroidism (2.31 +/- 0.11 mmol/L, 344), with subclinical
      hypothyroidism (2.32 +/- 0.10 mmol/L, n = 1290) and in healthy persons (2.31 +/-
      0.11 mmol/L, n = 4370). 173/13,387 persons had serum calcium levels < 2.1 mmol/L,
      among them 31 patients with hypoparathyroidism after strumectomy (31/592) and 2
      patients with primary hypoparathyroidism. 106/13,387 persons showed a S-Ca of >
      2.6 mmol/L, which in 30 cases was due to primary hyperparathyroidism. Of 55
      persons with S-Ca of > 2.6 mmol/L and without any other reason for
      hypercalcaemia, 31 were found to be in a hyperthyroid state. In conclusion, a
      clinically not relevant influence on S-Ca was demonstrated in patients with
      hyperthyroidism as compared with other thyroid diseases and individuals with no
      thyroid diseases. Measurement of S-Ca in every patient being referred to a
      thyroid outpatient department is recommended because of the frequent occurrence
      of postoperative hypoparathyroidism and primary hyperparathyroidism in this
      setting.

PMID- 11233473
TI  - Long-term stent implantation in a case of relapsing intrathoracic Ewing-sarcoma.
AB  - The overall prognosis of relapsing Ewing sarcoma is poor and therapeutic options
      can be limited by extensive chemotherapeutic pretreatment. We report on a case of
      a 27-year-old male, presenting with a large mediastinal mass and malignant
      pleural effusions. 5 years prior peripheral Ewing sarcoma had been treated
      according to the CESS 86 protocol. Relapse chemotherapy was initiated (CESS
      protocol) but tumor progression led to stenoses of both main bronchi. At this
      critical point, 2 Strecker tantal stents were placed endoscopically to prevent
      suffocation and provide the time for further chemotherapy, regardless of the poor
      overall prognosis. Complete remission was achieved by high-dose ifosfamide,
      surgery, radiotherapy and adjuvant ifosfamide. In spite of possible complications
      of long-term stent implantation, the stents were not removed until 4 years later
      when stent dislocation occurred. After removal, the stents were epithelialized
      and electron microscopy demonstrated structural integrity of the stent. The
      patient has remained in complete remission since (6 years).

PMID- 11233475
TI  - Is chronic lymphocytic leukemia a contraindication for radon and thermotherapy?-
      a case report.
AB  - A growing number of patients presenting for radon-thermotherapy have a history of
      malignant disease. The question as to whether malignancies in general are a
      contraindication for radon treatment or mild hyperthermia during spa therapy is
      still a subject of controversy. We report a patient with osteoarthritis and a
      frozen shoulder who repeatedly underwent speleotherapeutic radon and hyperthermia
      treatment in the gallery of the Gasteiner Heilstollen, Austria, despite
      concomitant chronic lymphocytic leukemia (B-CLL, Rai stage 0). After nine courses
      of radon-thermotherapy over eight years, no apparent negative impact on CLL was
      noted. The purpose of this case report is to encourage discussion as to whether
      CLL or other past or present malignancies must be considered a contraindication
      for spa treatment such as radon-thermotherapy.

PMID- 11233474
TI  - [Management of testicular intraepithelial neoplasia (TIN)--a review based on the
      principles of evidence-based medicine].
AB  - Testicular intraepithelial neoplasia (TIN; also called carcinoma in situ of the
      testis) is the uniform precursor of testicular germ cell tumors. There is general
      agreement on the biological significance of TIN, however, the treatment is still
      a matter of dispute. The present review summarizes the treatment options
      currently available. In general, the management of TIN has to be adapted to the
      particular clinical situation of the patient. Eradication of TIN usually implies
      the loss of fertility. Therefore, fertility aspects should be considered before
      any kind of treatment is employed. Usually, patients with TIN have only small
      residual potential of fertility. Nonetheless, individual patients may qualify for
      sperm banking or cryopreservation of testicular tissue for future sperm
      extraction (TESE) and assisted fertilization. The most common clinical situation
      is the case of contralateral TIN in the presence of unilateral testicular cancer.
      Low dose radiotherapy to the testis with 18 Gy is the standard management option
      in these patients. The same procedure may be applied to solitary testicles after
      partial orchiectomy for germ cell tumors. During follow-up, testosterone levels
      should be evaluated every six months. If chemotherapy is required due to
      metastatic disease of the primary tumor management of TIN should be deferred.
      After chemotherapy 30% of TIN cases will persist and approximately 42% will recur
      in the later course. Repeat biopsy should be done six months after completion of
      chemotherapy or later. Only in cases with persistent TIN additional radiotherapy
      should be administered. If one testicle is afflicted with TIN while the other
      testis is in healthy condition (conceivable in infertility cases or patients with
      primary extragonadal germ cell tumors), then the TIN-bearing testis should be
      excised. Radiotherapy is not feasible in these cases because of shielding
      problems with the healthy testis.

PMID- 11233476
TI  - [Comparative incidence of protrusive atheromatous plaques of the thoracic artery
      in patients with atrial fluter and atrial fibrillation].
AB  - Although it has been demonstrated recently that in patients with atrial
      fibrillation, protrusive atheromatous plaques of the thoracic aorta (thickness 4
      mm) and left atrial abnormalities such as thrombosis, spontaneous contrast and
      low atrial blood flow velocities carry an additional embolic risk, this has not
      yet been studied in atrial flutter. Out of 2493 patients undergoing
      transoesophageal echocardiography between September 1993 and December 1997, 271
      consecutive patients in atrial flutter (N = 41) or fibrillation (N = 230) for
      over 48 hours, underwent transoesophageal echocardiography before cardioversion.
      Patients with atrial flutter were compared with those with atrial fibrillation.
      Their characteristics were comparable with respect to age (68 +/- 13 and 67 +/-
      12 years respectively, p = 0.628), sex ratio (men 66 and 54% respectively, p =
      0.212), previous thromboembolic disease (5 and 15% respectively, p = 0.126). The
      incidence of protrusive aortic atheroma (12 and 11% respectively, p = 0.919), of
      spontaneous contrast in the thoracic aorta (15 and 14% respectively, p = 0.847)
      were identical in both groups. The left atrium was significantly smaller (3.1 +/-
      0.7 and 6 +/- 3 cm2 respectively, p = 0.001), spontaneous atrial contrast less
      frequent (17 and 37% respectively, p = 0.024) and the velocities of atrial
      emptying higher (47 +/- 10 and 30 +/- 10 cm/s respectively, p = 0.030) in
      patients with flutter compared with atrial fibrillation. There was no difference
      in left ventricular fractional shortening (30 +/- 10 and 33 +/- 13% respectively,
      p = 0.630), the presence of rheumatic valvular disease (5 and 12%, p = 0.301),
      left atrial diameter (43 +/- 7 and 45 +/- 8, p = 0.134), right atrial surface
      area (16 +/- 4 and 17 +/- 6 cm2, p = 0.384) or in intraatrial thrombosis (2 and
      3%, p = 0.888) respectively. These results show a high prevalence of protrusive
      atheroma of the thoracic aorta both in atrial flutter and in atrial fibrillation,
      and fewer left atrial abnormalities in patients with flutter.

PMID- 11233477
TI  - [Comparison of two indices of arterial distensibility: temporal apparitions of
      Korotkoff sounds and pulse wave velocy. A Doppler echocardiography and ambulatory
      blood pressure monitoring study].
AB  - Arterial distensibility, one of the factors influencing afterload, plays a role
      in the development of left ventricular hypertrophy. The QKd, the delay before the
      perception of the Korotkoff sounds, is an index of arterial distensibility
      available from ambulatory blood pressure monitoring. The pulse wave velocity
      (PWV), another index of arterial distensibility, can be measured by Doppler
      echocardiography. The aim of this study was to compare these two indices with
      haemodynamic parameters of arterial distensibility and to determine their
      relationship to left ventricular geometry and function. Sixty-two consecutive
      patients, with and without cardiac disease, underwent simultaneous Doppler
      echocardiography and ambulatory blood pressure monitoring. A correlation was
      observed between QKd and PWV (N = 53, p = 0.007, r = 0.37). The QKd and PWV were
      correlated to the absolute index of arterial distensibility (systolic index/pulse
      pressure) (N = 51, p < 0.001, r = 0.48). QKd was correlated with indices of left
      ventricular function such as EF (N = 55, p < 0.001, r = 0.66) or the systolic
      pressure/end systolic dimension ratio (N = 54, p < 0.001, r = 0.75). When the
      ejection time was subtracted from QKd, only the end systolic pressure/end
      systolic dimension remained significantly correlated (N = 37, p = 0.005, r =
      0.40). The authors conclude that PWV and QKd were correlated and were also
      correlated with indices of arterial distensibility. QKd is a composite index of
      left ventricular function and arterial distensibility. Doppler echocardiography
      and ambulatory blood pressure monitoring provide a non-invasive assessment of the
      aorta/LV couple.

PMID- 11233478
TI  - [Measurement of left atrial and ventricular volumes in real-time 3D
      echocardiography. Validation by nuclear magnetic resonance].
AB  - The measurement of the left ventricular ejection fraction is important for the
      evaluation of cardiomyopathy and depends on the measurement of left ventricular
      volumes. There are no existing conventional echocardiographic means of measuring
      the true left atrial and ventricular volumes without mathematical approximations.
      The aim of this study was to test anew real time 3-dimensional echocardiographic
      system of calculating left atrial and ventricular volumes in 40 patients after in
      vitro validation. The volumes of the left atrium and ventricle acquired from real
      time 3-D echocardiography in the apical view, were calculated in 7 sections
      parallel to the surface of the probe and compared with atrial (10 patients) and
      ventricular (30 patients) volumes calculated by nuclear magnetic resonance with
      the simpson method and with volumes of water in balloons placed in a cistern.
      Linear regression analysis showed an excellent correlation between the real
      volume of water in the balloons and volumes given in real time 3-dimensional
      echocardiography (y = 0.94x + 5.5, r = 0.99, p < 0.001, D = -10 +/- 4.5 ml). A
      good correlation was observed between real time 3-dimensional echocardiography
      and nuclear magnetic resonance for the measurement of left atrial and ventricular
      volumes (y = 0.95x - 10, r = 0.91, p < 0.001, D = -14.8 +/- 19.5 ml and y = 0.87x
      + 10, r = 0.98, P < 0.001, D = -8.3 +/- 18.7 ml, respectively. The authors
      conclude that real time three-dimensional echocardiography allows accurate
      measurement of left heart volumes underlying the clinical potential of this new 3
      D method.

PMID- 11233479
TI  - [Incidence and timing of thyroid dysfunction with long-term amiodarone therapy].
AB  - The aim of this retrospective study was to assess the incidence, timing and
      classical presentations of thyroid dysfunction in patients treated long-term with
      amiodarone. Ninety patients (sex ratio M/W 67/33, mean age 71 years) were
      followed up for 48 months. The daily dose of amiodarone was 200 mg after loading
      doses during the hospital stay for atrial fibrillation. The average treatment
      period was 33 +/- 19 months. Hypothyroidism, observed in 5.5% of cases, occurred
      at variable intervals with few clinical manifestations. Hyperthyroidism was more
      common (12.2%), occurred increasingly with time, and was clinically symptomatic
      with recurrent supraventricular arrhythmias in 36% of cases. Long-term amiodarone
      therapy causes undesirable thyroid side-effects for nearly 1 out of 5 patients.
      Hyperthyroidism is more common than hypothyroidism and may be explained by
      increased iodine intake. The increasing incidence of hyperthyroidism with time
      suggests a cumulated dose relationship, a situation which is not observed with
      hypothyroidism.

PMID- 11233480
TI  - [Coronary prosthesis implantation. Immediate and mid-term results].
AB  - The aim of this study was to evaluate the clinical events occurring after
      coronary stenting in a series of 318 consecutive patients treated in 1997.
      Hospital follow-up was by gathering all the data in the hospital record and
      medium-term follow-up was performed by questionnaire filled with the help of the
      patient, the attending physician and the referring cardiologist. The primary
      clinical success rate was 95.6% and the clinical follow-up rate was 98.7%. The
      follow-up period was at least 16 months (mean 22 +/- 6 months). The restenosis
      rate was 15% in the remaining population (318-7 deaths and 4 lost to follow-up)
      and 47% in the population undergoing control coronary angiography. No major
      clinical cardiac events (death, myocardial infarction or revascularisation) were
      observed in 80.5% at 1 year and 79% at 22 months. Twenty per cent of the
      remaining population had no non-invasive paraclinical investigations for
      myocardial ischaemia after coronary stenting. These results are comparable to
      those of the literature, indicating excellent feasibility of this technique and
      the fact that, programmed or not, coronary stenting is a safe procedure
      confirming its value in what has become everyday practice. Nevertheless, this
      experience did highlight certain lapses in medical follow-up and patient
      information.

PMID- 11233481
TI  - [Operative risk factors and polyvalvular cardiac surgery].
AB  - The aim of this study was to identify risk factors for morbidity and mortality in
      cardiac valvular surgery. Two hundred and fifty-four patients underwent
      polyvalvular surgery between May 1996 and December 1998. The mean age was 36.8
      years (range 4-66 years) and the group comprised 148 women. Two subgroups were
      defined: the first (184 patients), characterised by associated mitral and
      tricuspid valve disease: the second (70 patients), characterised by associated
      mitral and aortic valve disease with a tricuspid lesion in about half the cases.
      The risk factors of morbidity and mortality analysed were: Clinical: previous
      history of cardiac failure, NYHA classification, atrial fibrillation and
      cardiothoracic index. Doppler echocardiographic: left ventricular end systolic
      dimension > 50 mm, left ventricular and diastolic dimension > 70 mm, fractional
      shortening < 28%, ejection fraction < 40%: systolic pulmonary artery pressure >
      30 mmHg. Haemodynamic: capillary wedge pressure > 20 mmHg, systolic pulmonary
      artery pressure > 30 mmHg. The authors identified three statistically significant
      risk factors for operative morbidity and mortality in polyvalvular cardiac
      surgery: Previous history of one or more episodes of cardiac failure NYHA
      functional Classes III or IV fractional shortening < 28%. The morbidity and
      mortality were lower when patients were operated before these poor prognostic
      factors were observed.

PMID- 11233482
TI  - [The ilio-femoral approach: an alternative for implanting permanent cardiac
      pacemakers. Three case reports].
AB  - Permanent endocavitary cardiac pacing is a widely used therapeutic method. The
      implantation of pacing catheters is usually performed by the supracardiac veins,
      the epicardial approach being the classical alternative. The ilio-femoral
      approach is a third possibility. The authors report three cases in which this
      approach was used. The implantations were performed under general anaesthesia
      with an abdominal pacemaker. In two cases, atrial and ventricular catheters were
      implanted. After an average of 19 months' follow-up, no short or long-term
      complications were observed: displacement or fracture of the pacing catheter,
      infection, venous thrombosis, threshold elevation. These results show that this
      is a safe and feasible alternative to implantation by the traditional or
      epicardial techniques when these approaches cannot be used.

PMID- 11233483
TI  - [Use of heparin in unstable angina and non-Q-wave infarction].
AB  - The limitations of conventional treatment by non-fractionated heparin (NFH) in
      unstable angina and non-Q wave infarction with a serious adverse event rate
      (infarction and/or death) of 7 to 9% at 30 days have led to research in the use
      of low molecular weight heparin (LMWH). In 1995, Gurfinkel et al reported the
      superiority of the association aspirin-LMWH (Nadroparine) over a more classical
      treatment with aspirin alone or the association of aspirin-NFH in unstable angina
      and non-Q wave infarction. In 1996, the FRISC trial confirmed the value of LMWH
      (Dalteparine). However, this trial compared the LMWH with placebo. In 1997, the
      FRIC trial showed that dalteparine was equivalent to NFH. However, the ESSENCE
      and TIMI 11B trials reported the superiority of LMWH (Enoxaparine) over NFH in
      unstable angina and non-Q wave infarction. Compared with NFH, a significant 20%
      reduction in the composite criterion (death-non-fatal infarction) was observed
      with enoxaparine from the 2nd day up to day 43, without an increase in serious
      haemorrhagic complications. More recently, FRISC II showed the value and
      indicated the duration of treatment of LMWH, dalteparine, with respect to the
      chosen "invasive" or "non-invasive" strategies of revascularisation. The
      subcutaneous administration, absence of biological controls, the predictability
      of the anticoagulation and the better tolerance of the LMWH are powerful
      arguments in favour of their use in unstable angina and non-Q wave infarction.
      Thus, the LMWH have taken their place in the treatment of unstable coronary
      disease where the therapeutic arsenal is in constant evolution.

PMID- 11233484
TI  - [Left ventricular functional imagery by magnetic resonance. Applications and
      developments].
AB  - Technical developments have considerably reduced the acquisition time and have
      improved the quality of magnetic resonance imaging. The recent recommendations of
      the European Society of Cardiology place MRI in the front line of investigations
      for the diagnosis and evaluation of congenital heart disease, cardiac tumours and
      pathology of the pericardium and great vessels. With the possibility of obtaining
      oblique planes in all 3 dimensions, MRI is the reference for the measurement of
      left ventricular mass, volumes, and ejection fraction, with the major advantage
      of not depending on hypotheses of left ventricular geometry. In addition to these
      known applications, the development of functional cardiac MRI has led to
      significant advances in the study of regional myocardial function and perfusion.
      The aim of this article is to discuss present indications and the potential
      developments of functional cardiac MRI, focusing on the quantitative evaluation
      of myocardial function and perfusion.

PMID- 11233485
TI  - [Prophylactic value of automatic implantable defibrillators: a case report of a
      patient with asymptomatic Brugada syndrome].
AB  - The authors report the case of an asymptomatic 32 year old man with no family
      history of sudden death but with ECG changes suggesting Brugada's syndrome. He
      underwent implantation of an automatic defibrillator after inducible syncope
      ventricular fibrillation had been demonstrated during electrophysiological
      investigation. The later occurrence of three episodes of ventricular fibrillation
      treated by the defibrillator confirmed a posteriori the logic of this therapeutic
      approach.

PMID- 11233486
TI  - [Prognosis and risk evaluation of postoperative coronary patients (PERISCOP).
      Methodology and study population characteristics].
AB  - The aim of the PERISCOP study was to evaluate the predictive value of
      cardiological investigations performed after recent coronary bypass surgery with
      regards to cardiac event and mortality at one year. The treatment of lipid
      abnormalities was also analysed. This first article describes the methodology and
      patient characteristics at inclusion. This prospective national multicenter trial
      included 2065 patients (86% men) with an average age of 63.1 +/- 9.9 years. The
      number of diseased vessels was 2.6 +/- 0.6. Preoperative left ventricular
      function was normal (ejection fraction 60 +/- 13%). Revascularisation was
      complete in 73% of cases (22% of arterial grafts). The cardiological
      investigations were performed at Day 20 +/- 10 after surgery. The duration of
      exercise on stress testing was 429 +/- 170 seconds. It was positive or doubtful
      in 9% of cases. Ventricular arrhythmias were observed in 6.5% of cases. The blood
      pressure response was abnormal in 6% of cases. Holter monitoring showed a median
      number of ventricular extrasystoles over 24 hours of 44. Three per cent of
      patients had one episode of ventricular tachycardia and 7% had ischaemic
      episodes. The echocardiographic index of segmental contractility was on average
      1.75 (ejection fraction: 52.6%). The lipid analysis performed at one month, under
      lipid therapy in 34% of cases, showed a total cholesterol level at 1.91 +/- 0.10
      g/l, an LDL-cholesterol of 1.27 +/- 0.08 g/l. The therapeutic target (LDL
      cholesterol < 1 g/l) was attained in 46% of cases with treatment and in 18% of
      cases without treatment.

PMID- 11233487
TI  - [Drug for the treatment of sleep disorders--review].
AB  - For the treatment of insomnia/sleep disturbances, drugs are indicated only if non
      drug-procedures alone are not sufficiently successful or not successful at all.
      To facilitate sleep, sedative-hypnotic agents are used clinically. Because of
      favorable risk-benefit ratio, non-benzodiazepines with benzodiazepine-like action
      (zolpidem, zopiclon) or benzodiazepines themselves (dependent on their
      pharmacokinetic profil) are administered in the most cases. Sedative-hypnotic
      drugs reducing the electric activity of the CNS sufficiently to produce coma and
      even death are not recommended at present. To assess the clinical relevance of
      amino acid L-tryptophan for the treatment of insomnia/sleep disturbances, more
      controlled clinical studies are necessary. The nonprescription antihistamines
      (Doxylamin, Diphenhydramin) are only suitable for short-term administration in
      adults. Under certain conditions, antidepressant and antipsychotic drugs can be
      taken. Because of potential risks, the intake demands caution. Different herbal
      remedies are recommended, but only for extracts of valerian a sleep-inducing
      effect can be assumed. Melatonin, an endogenous hormone and tryptophan-metabolite
      is thought to be involved with the sleep-wake cycle. Therefore the exogenous
      intake of melatonin may influence vigilance and sleep. This is particularly true
      for patients with jet-lag symptoms.

PMID- 11233488
TI  - [Benzodiazepines and benzodiazepine receptor agonists in the treatment of sleep
      disorders--importance and dangers. Evaluation from the clinical medical view].
AB  - After first giving an overview about the epidemiological situation, the
      indications and contraindications of benzodiazepines as well as those of the
      newer short-time hypnotics zolpidem and zopiclone are reviewed. Premises for
      their use and alternatives to their application are discussed and the different
      substances are discussed for their clinical use. Problems of drug abuse and
      addiction are accounted in detail for these effective and little toxic agents.
      Finally recommendations for treatment are given to contribute to a more critical
      and scientific way of prescribing these valuable, though problematic, drugs.

PMID- 11233489
TI  - [Treatment of the neurological sleep disorders restless legs syndrome and
      narcolepsy].
AB  - Pharmacological therapies are presented for two typical neurological sleep-wake
      disorders, restless legs syndrome (RLS) and narcolepsy. The individual discomfort
      caused by RLS and the accompanying problems with initiating and maintaining sleep
      often require a therapy with L-dopa and dopamine agonists. Positive treatment
      effects on sensory and motor symptoms have been shown in open trials and
      controlled studies. Development of time shift and/or augmentation of symptoms is
      a problem of L-dopa therapy. Further efficient drugs are opioids and
      benzodiazepines. The therapy of narcolepsy depends on its severity and the
      pattern of the symptoms. Excessive daytime sleepiness and sleep attacks are the
      most impairing symptoms, which are difficult to treat. These symptoms require an
      optimal combination of CNS stimulants with regular napping. Cataplexy and other
      REM sleep associated symptoms are effectively treated with REM sleep suppressing
      antidepressants.

PMID- 11233490
TI  - [Drugs for the treatment of sleep disturbances--neuroleptics and
      antidepressants].
AB  - Antidepressants and neuroleptics are an essential tool for the treatment of sleep
      disturbances associated with defined psychiatric disorders. They may also be used
      2nd choice for the treatment of psychophysiological insomnia. There is some
      evidence of a "causal" therapeutic action of some antidepressants in sleep
      disorders. Here, antidepressants and neuroleptics ought to be given in severe
      and/or chronic cases and to patients which are particularly vulnerable to the
      addictive potential of benzodiazepines and their analogues. They may be given
      during routine wash-out periods for benzodiazepines or loss of action, and for
      the treatment of psychiatrically related syndromes. Because of the higher
      incidence of aversive, even serious side-effects, careful benefit-risk
      evaluations and intense control studies are warranted.

PMID- 11233491
TI  - [Standards in clinical diagnosis].

PMID- 11233492
TI  - [Phytochemicals as means to induce sleep].
AB  - Phytopharmacons are widely used in Germany. Whereas St. John's wort extracts are
      prescribed for the treatment of mild forms of depression and kava-kava for
      unspecified anxiety syndromes, hop, balm, lavender, passiflora and valerian are
      traditionally administered against nervousness and sleep disturbances. Controlled
      clinical trials are only available for valerian. However, no sleep inducing
      potential of valerian was observed, only a certain positive effect on daytime
      mood. Therefore, the mentioned phytopharmacons cannot be recommended for the
      treatment of sleep disturbances.

PMID- 11233493
TI  - [Theophylline in the treatment of sleep-related breathing disorders].
AB  - The methylxanthine derivates are known to have respiratory stimulant properties.
      Therefore theophylline is used in sleep related disturbances of breathing.
      Theophylline reduces central apneas and periodic breathing in infants. The
      efficiency of theophyllin is confirmed in reducing central apneas in patients
      with neurologic diseases or Cheyne Stokes breathing in patients with congestive
      heart failure. In patients with obstructive sleep apnoea the effect of
      theophylline is doubtful. An effect of therapy exists in some mild forms of sleep
      apnoea (apnoea index < 20/h total sleep time). Further studies are necessary to
      investigate the precise mechanism of of theophylline in obstructive sleep apnoea.

PMID- 11233494
TI  - [Melatonin: is there a rationale for the clinical use of this hormone in sleep
      therapy?].
AB  - Melatonin, the hormone of the pineal gland, is under discussion as multipotent
      hormone for different indications. The question whether there is a therapeutical
      benefit for all these indications could not be evaluated, because more clinical
      studies are needed. Based on the data of basic research as well as first clinical
      experience, the use of melatonin to treat sleep disorders caused by a deficit of
      melatonin might be appropriate. Other indications, derived from animal studies
      where the results often could not be applied to humans, have still to be proved.
      Given the fact that melatonin is not an approved product, only an intent to treat
      approach is allowed where it might by useful to document the melatonin deficit
      and to use a selected and certificate product.

PMID- 11233495
TI  - [Diagnosis and classification of sleep disorders].
AB  - When sleep was recognized as an active process which is regulated by the
      interaction of homeostatic and circadian systems a new understanding of sleep
      disturbances set in, and sleep medicine developed as a new medical speciality. An
      internationally recognized classification system was developed which allows to
      diagnose the different sleep disturbances reliably. Sleep disorders comprise (a)
      dysregulations of the sleep-wake system (insomnias, hypersomnias, narcolepsy,
      parasomnias), (b) sleep associated disturbances of functional systems (for
      example sleep apnea, restless legs syndrome), (c) disturbances of the circadian
      sleep-wake rhythm, and (d) sleep disturbances in association with other organic
      or psychiatric illnesses. The present contribution shows the diagnostic
      procedures for four main sleep disorders, namely insomnia, obstructive sleep
      apnea (OSAS), restless legs syndrome (RLS), and narcolepsy.

PMID- 11233496
TI  - [Poisoning with sleep supporting drugs].
AB  - Emergencies caused by acute poisoning amount to 3-5% of the actions carried out
      by the emergency medical service. Sleep supporting drugs have a 35% part in the
      acute drug-induced poisoning, primarily within the framework of suicidal or
      parasuicidal actions. In this case, benzodiazepines occupy a top position,
      followed by H1-antihistaminic agents with strong sedative effects, and the so
      called anxiolytic agents of the "second generation". In general, intoxication
      with sleep supporting drugs lead to disturbances of consciousness with different
      degrees of seriousness. Careful (external) anamnesis, inspection of the
      environment and clinical investigations could be helpful to evaluate the
      diagnosis. Hypoglycemia and neurological illnesses are to be excluded
      differential diagnostically. Preclinical therapy follows the "five finger rule"
      (stabilization of the vital functions, detoxification, antidote therapy,
      asservation, transportation). Specific procedures (preclinical stomach lavage,
      antidote therapy) are indicated in rare cases, only (mainly mixed intoxication
      with ethanol). Subsequent therapeutic procedures under clinical conditions are
      demonstrated using selected examples.

PMID- 11233497
TI  - [Diagnosis of hyperthyroidism].
AB  - The clinical signs and symptoms of the patient are the background for further
      examination procedures. A dysfunction of the thyroid gland can be safely excluded
      when the TSH level is within the normal range. A hyperthyroidism can be proven
      when TSH is suppressed and T3 and T4 levels, respectively, are elevated. However,
      the concentrations of T3, T4 (inclusive free T3 and free T4) and TSH are not only
      dependent on the thyroid status, but also on various extrathyroidal influences.
      Therefore awareness of accompanying diseases and of medications is necessary in
      order to avoid errors of interpretation. Different forms of hyperthyroidism have
      to be distinguished. The differentiation between Graves' disease and the
      functional autonomy (toxic nodular goiter) is of practical importance. Several
      methods--apart from precise clinical examination--are helpful. When Graves'
      disease is suspected TSH-receptor- and TPO-antibodies should be measured and an
      ultrasound obtained. When an autonomy is suspected, a szintigraphy as well as
      ultrasound should be undertaken. The laboratory methods are of high precision and
      sensitivity. There use is dependent on the clinical diagnostic problem, which
      also determines the extend and expenditure of the diagnostic procedures. These
      considerations are necessary also for economical reasons.

PMID- 11233498
TI  - AMS efforts defend children's health care.

PMID- 11233499
TI  - Legislative advocacy--everyday, all day.

PMID- 11233500
TI  - To merge or not to merge?

PMID- 11233501
TI  - Managing diabetes mellitus.

PMID- 11233502
TI  - Suspected insulin anaphylaxis and literature review.
AB  - Insulin allergy is a well-documented complication of insulin therapy. A 67-year
      old man presented with symptoms suggestive of insulin anaphylaxis. In an attempt
      to allow him to continue insulin therapy, he underwent a desensitization
      protocol. During the protocol, he again experienced symptoms suggestive of
      anaphylaxis. An analysis of his case is presented in the context of current
      literature. All physicians treating patients with insulin should be aware of this
      serious complication.

PMID- 11233503
TI  - Older female inpatients in Arkansas.
AB  - The purpose of this study was to examine age and Major Diagnostic Categories
      (MDCs) and compare the variables to mortality and length of stay among inpatient
      women age 50 and over. Archival statistical data were obtained for 2,238
      inpatients in a private, nonprofit hospital in 1998. The ages ranged from 50 to
      107 years old, with a mean age of 71.21 years. Quantitative analyses were
      conducted to examine the data from a private, nonprofit hospital and determine if
      there were significant relationships between age, major diagnostic category,
      length of stay, and mortality in older women. The MDC distribution indicated that
      the highest frequency of diseases and disorders were in the following three
      systems: circulatory system, musculoskeletal system and connective tissue, and
      the digestive system. The average length of stay was 8.01 days. The 30-day
      readmission percentage and the 365-day readmission percentage were 12.24% and
      28.02%, respectively. The mortality rate was 6%. In addition, 63.97% went home
      after discharge, and 67.07% were Medicare recipients. The risk of musculoskeletal
      diseases and disorders increased with age (p = .0001). The conditional
      probability of death was nearly nine times higher for the diseases of the nervous
      system, myeloproliferative diseases and disorders, poorly differentiated
      neoplasms and respiratory diseases. As age increased, the probabilities of a long
      hospital stay decreased. The mortality analyses found that the lowest
      probabilities of survival were in categories of myeloproliferative diseases and
      disorders, poorly differentiated neoplasms, and infectious and parasitic
      diseases. According to current health statistics, our society is getting older.
      Not only are people living longer, they are accessing more health care (American
      Association for World Health, 1999). Overall, the average life expectancy at
      birth has been identified at 76.5 years. The female has a longer life expectancy
      than the male, averaging 5.8 years longer. The highest life expectancy has been
      identified in the white female, who can expect to live to 79. The black woman has
      the second-highest life expectancy, 74.7 years. Peters, Kochanek, and Murphy
      reported an all-time-low age-adjusted death rate for the United States and a
      continuing trend in the decline in mortality for all age groups. With a growing
      number of people living longer, there is a need to know about the most common
      health issues that affect quality of life. The top three national causes of death
      in older Americans were diseases of the heart, malignant neoplasms, and
      cerebrovascular diseases/stroke. Arkansas health statistics mirror the national
      statistics. In April 1999, the Arkansas Department of Health reported that 30.5%
      percent of all female deaths were caused by heart disease. Malignant neoplasms
      were responsible for 20.1%, followed by cerebrovascular diseases at 10.8%. Other
      than three Connecticut hospital studies that explored the relationship of
      diagnosis code, mortality, and readmission, research is meager in this area.
      There is a need for hospital-based research that addresses the diagnosis
      categories and the relationship to age and other variables.

PMID- 11233504
TI  - [Acute poisoning of pigs with hydrogen sulfide as a result of acidification of
      slurry on a pig farm].
AB  - On a fattening pig farm all 582 animals died of peracute intoxication with
      hydrogen sulphide (H2S). The accident took place after 6000 litres of lactic acid
      (41.5 mass %) was dumped in the slurry pit. The volume of released gas was about
      575 m3. This resulted in sudden spreading by high pressure of a lethal
      concentration of hydrogen sulphide to all compartments of the pig house. Analysis
      of the situation indicated that the level of hydrogen sulphide was 7870 ppm.

PMID- 11233505
TI  - [Predecessors: veterinarians from earlier times (42). Jean Joseph Henry Toussaint
      (1847-1890)].

PMID- 11233506
TI  - [The 'udder health panel' discusses the milking robot and udder health].

PMID- 11233507
TI  - [Destruction of all animals on the farm after diagnosis of BSE in one animal. Is
      that a good strategy?].

PMID- 11233508
TI  - [A reprimand and 2500 guilders fine for off-label use of veterinary drugs].

PMID- 11233509
TI  - [Therapy and prognosis of appendicular osteosarcoma in the dog].

PMID- 11233510
TI  - [BSE in companion animals].

PMID- 11233511
TI  - [Automated detection of estrus and mastitis in dairy cows].
AB  - The development and test of detection models for oestrus and mastitis in dairy
      cows is described in a PhD thesis that was defended in Wageningen on June 5,
      2000. These models were based on sensors for milk yield, milk temperature,
      electrical conductivity of milk, and cow activity and concentrate intake, and on
      combined processing of the sensor data. The models alert farmers to cows that
      need attention, because of possible oestrus or mastitis. A first detection model
      for cows, milked twice a day, was based on time series models for the sensor
      variables. A time series model describes the dependence between successive
      observations. The parameters of the time series models were fitted on-line for
      each cow after each milking by means of a Kalman filter, a mathematical method to
      estimate the state of a system on-line. The Kalman filter gives the best estimate
      of the current state of a system based on all preceding observations. This model
      was tested for 2 years on two experimental farms, and under field conditions on
      four farms over several years. A second detection model, for cow milked in an
      automatic milking system (AMS), was based on a generalization of the first model.
      Two data sets (one small, one large) were used for testing. The results for
      oestrus detection were good for both models. The results for mastitis detection
      were varying (in some cases good, in other cases moderate). Fuzzy logic was used
      to classify mastitis and oestrus alerts with both detection models, to reduce the
      number of false positive alerts. Fuzzy logic makes approximate reasoning
      possible, where statements can be partly true or false. Input for the fuzzy logic
      model were alerts from the detection models and additional information. The
      number of false positive alerts decreased considerably, while the number of
      detected cases remained at the same level. These models make automated detection
      possible in practice.

PMID- 11233512
TI  - [The Guideline Manual. Development and implementation of guidelines in medicine].

PMID- 11233513
TI  - 13CO2 breath tests and stable isotopes for investigating gastrointestinal
      functions.

PMID- 11233514
TI  - Evaluation of the 13C-aminopyrine breath test using nondispersive infrared
      spectrometry.
AB  - OBJECTIVE: The aim of the study was to assess the value of the 13C Aminopyrine
      Breath Test (ABT) when performed using the NonDispersive InfraRed Spectrometry
      (NDIRS), which is a simple and cheap alternative to the mass spectrometry.
      METHODS: The results obtained by using the NDIRS method for performing the ABT
      were compared to the results obtained by a reference method, the 14C Aminopyrine
      Breath Test. For this purpose, in 32 patients admitted for various liver
      problems, an ABT was performed by using the 2 methods simultaneously. The
      repeatability of the results obtained at 120 minutes by the NIDRS method as
      compared to the 14C test was assessed by the method of Bland and Altman. RESULTS:
      The mean of difference between the results obtained by both methods at 120
      minutes was 0.06 +/- 0.46. The coefficient of repeatability between the two tests
      was 0.92 for a confidence interval of 95%. A good correlation (r = 0.93) was
      found between all individual results obtained in breath samples at different
      times of collection (30, 60, 90, 120 minutes), and between the results obtained
      at 120 minutes for both 13C and 14C tests (r = 0.94). CONCLUSION: The 13C ABT
      performed using NDIRS is a valid alternative to the 14C technique in routine
      clinical practice.

PMID- 11233515
TI  - Oesophageal self expanding metal stents. Preliminary report about covered and non
      covered types.
AB  - OBJECTIVE: The aim of this study was to evaluate the effectiveness and
      complications rate of covered and non-covered self expanding metal stents in the
      palliative treatment of oesophageal dysphagia. DESIGN: In this retrospective non
      randomized study, we evaluated 11 non-covered and 17 covered stents of different
      types. RESULTS: Grade of dysphagia and improvement after treatment were similar
      in both groups, all the seven fistulas were sealed by covered stents. Covered
      stents seem to be safer regarding the rate of life-threatening complications and
      reinterventions. In contrast to published studies, bleeding was our major
      complication with death related in half of these patients. Aorto-Oesophageal
      fistula was proved by autopsy in two of them. CONCLUSIONS: Covered stents lead to
      less drawbacks than non-covered ones and seem to be recommended in the palliation
      of oesophageal dysphagia even in the absence of fistula.

PMID- 11233516
TI  - Ischemia/reperfusion injury of the liver: pathophysiologic hypotheses and
      potential relevance to human hypoxic hepatitis.
AB  - For the last decade, numerous experimental studies have demonstrated that the
      main part of liver injury caused by low or no flow states does not occur at the
      time of hypoxia, but during reperfusion. These experimental studies have a
      crucial clinical impact, because ischemia/reperfusion injury is involved in
      situations such as temporary vascular exclusion during liver surgery for trauma
      or tumors, preservation injury before liver transplantation, and liver cell
      necrosis observed in hypoxic (ischemic) hepatitis. The aim of the present review
      is to clarify the sequence of pathophysiological events responsible for
      ischemia/reperfusion injury of the liver, and to examine the potential
      contribution of liver ischemia/reperfusion injury to the syndrome of human
      hypoxic hepatitis.

PMID- 11233517
TI  - Lamivudine for the treatment of chronic hepatitis B.
AB  - Lamivudine (Zeffix) is the first of a new class of antiviral agents to become
      available for the treatment of chronic hepatitis B. The results of controlled
      clinical trials indicate that in most patients, lamivudine improves necro
      inflammatory liver disease, reduces the progression of hepatic fibrosis,
      normalises serum alanine aminotransferase, and enhances hepatitis B e antigen
      (HBeAg) seroconversion. For patients with HBeAg-positive chronic hepatitis B, one
      year of lamivudine therapy results in HBeAg seroconversion rates similar to those
      obtained with a standard course of interferon-alpha. Moreover, results from two
      and three years of lamivudine therapy show that the cumulative HBeAg
      seroconversion rate continues to increase with extended lamivudine therapy. Even
      in the absence of HBeAg seroconversion, lamivudine therapy leads to improvements
      in liver disease in many patients. HBV strains (YMDD variants) with reduced in
      vitro sensitivity to lamivudine were detected in some patients after at least 9
      months therapy. Although the clinical benefits to lamivudine were greatest for
      those patients who remained free of YMDD variants, one year of lamivudine therapy
      led to improvements in most response parameters compared with placebo, regardless
      of whether YMDD variants were detected. Controlled and open-label studies show
      that lamivudine may provide similar benefits to other important groups of
      patients with chronic hepatitis B, including those with pre-core mutant disease
      and those with hepatic decompensation. Lamivudine was well tolerated in all
      patient groups studied. The incidence of adverse events was consistently similar
      in patients who received lamivudine compared with those given placebo. In
      conclusion, extensive clinical data provide evidence that lamivudine is a well
      tolerated, effective, and convenient medicine for patients with chronic hepatitis
      B.

PMID- 11233518
TI  - Hepatitis A and hepatitis B vaccination of patients with chronic liver disease.

PMID- 11233519
TI  - Fibrosis of liver, pancreas and intestine: common mechanisms and clear targets?
AB  - Chronic diseases of the liver, pancreas, intestine, kidneys, skin and lungs are
      usually accompanied by scarring. Loss of organ function is often progressive
      despite the use of immunosuppressive, antiviral or antiinflammatory agents.
      Therefore, well tolerated antifibrotic therapies are urgently needed. The targets
      for such therapies are activated mesenchymal cells that synthesize an excess of
      matrix proteins and resemble the myofibroblasts of healing wounds. These cells
      derive from normally quiescent fibroblasts or smooth muscle cells and from
      stellate cells of liver and pancreas. Their activation is triggered and
      maintained by mechanical stress and several fibrogenic modulators and cytokines.
      Some agents inhibit myofibroblast proliferation and collagen synthesis in vitro,
      but only few of them are effective in vivo. Potential antifibrotic drugs have
      been tested mainly in models of liver fibrosis. In the suitable rat model of
      biliary fibrosis, an antifibrotic effect was demonstrated for silymarin, a
      defined mixture of flavonoids, and to a lesser degree for pentoxifylline. A spin
      off of the large multicenter trials for hepatitis C is the finding that
      interferon-alpha given for 6-12 months may halt or reverse fibrosis, even in
      virological non-responders. This has to be proven in prospective randomized
      trials. Specific inhibitors of the endothelin-A-receptor which are orally
      available can suppress liver collagen accumulation by 40-60%. Other strategies
      aim at inhibition of the profibrogenic cytokines TGF-beta or connective tissue
      growth factor. Effective drug targeting to the fibrogenic liver cells is now
      possible by use of cyclic peptides that bind to receptors which are specifically
      upregulated on activated stellate cells. Blockade of such activation receptors
      can induce stress-relaxation which reverts the fibrogenic cells to a fibrolytic,
      collagen degrading phenotype. Fibrosis has been discovered as a novel target for
      the pharmaceutical industry. This implies the use of combinatorial chemistry and
      an automatized screening machinery, greatly speeding up the design and selection
      of specific antifibrotic agents. Combined with the rapidly evolving validation of
      serological markers of fibrogenesis and fibrolysis unforeseen progress in the
      treatment of organ fibrosis can be expected.

PMID- 11233520
TI  - Contribution of morphology for the comprehension of mechanisms of fibrosis in
      inflammatory enterocolitis.
AB  - Strictures are a common complication of Crohn's disease and an indication for
      surgery in approximately 50% of patients. Morphologic studies have shown that
      fibrosis of the submucosa and muscularis propria are common in Crohn's disease,
      especially in strictures. Immunohistochemical and in situ hybridization studies
      have demonstrated a marked increase of various subtypes of collagens in Crohn's
      disease. Collagens type I and III are present in ulcerated areas where they
      appear around capillaries and in a linear deposition at the junction between the
      granulation tissue and the necrotic debris. Collagens type IV and V show a
      prominent perivascular expression, increased deposition in the muscularis propria
      and increased expression around ganglia. Initiation and maintenance of the
      connective tissue changes are related with the inflammatory infiltrate.
      Inflammatory cells can further alter smooth muscle proliferation and migration
      and promote the formation of myofibroblasts. These alterations together with
      increased collagen deposition are involved in the complex process of strictures
      and bowel wall alterations in Crohn's disease.

PMID- 11233521
TI  - Genetics of Crohn's disease behaviour.
AB  - Crohn's disease is probably an heterogeneous entity. This heterogeneity may be
      linked to either genetics or environment. In particular the behaviour of the
      disease, i.e. the tendency to develop stricturing and/or penetrating lesions, may
      be linked to the genetic background. While epidemiological and clinical data
      suggest the relevance of these behavioural classifications, the progresses in the
      characterization of the immuno-inflammatory reaction in the bowel wall shed a new
      light on possible candidate genes for these genetic predispositions to various
      Crohn's disease behaviours. Association studies an linkage analysis focusing on
      growth factors, metalloproteinases and their tissue inhibitors as well as
      cytokines may bring new interesting data in this field.

PMID- 11233522
TI  - Helicobacters of possible zoonotic origin: a review.
AB  - Since the isolation of Helicobacter pylori, many new Helicobacter species have
      been identified from the gastrointestinal tract in humans and animals. In humans,
      a spiral organism different from H. pylori and provisionally named "Helicobacter
      heilmannii", has been associated with gastritis, gastric ulceration and to a
      lesser degree, gastric cancer. In addition Helicobacter cinaedi, Helicobacter
      fennelliae, Helicobacter pullorum and "Flexispira rappini" have been isolated
      from cases of enteric disease, bacteremia and pneumonic illness. In the biliary
      tract, the presence of Helicobacter bilis, Helicobacter pullorum and "Flexispira
      rappini" has been demonstrated. Morphological, epidemiological and genotypic data
      suggest the involvement of animal helicobacters in these infections. In this
      paper, a review of the literature addressing the current knowledge about
      epidemiology, diagnosis, pathogenesis and therapy of these infections is given.

PMID- 11233523
TI  - Evidence based medicine and extradigestive manifestations of Helicobacter pylori.
AB  - A putative pathogenetic role has been ascribed to Helicobacter pylori in several
      extradigestive diseases, including vascular (atherosclerosis and ischaemic heart
      disease, primary Raynaud phenomenon, primary headache), autoimmune (Sjogren's
      syndrome, Henoch-Schonlein purpura, autoimmune thyroiditis, idiopathic
      arrythmias, Parkinson's disease, nonarterial anterior optic ischemic neuropathy),
      and skin diseases (chronic idiopathic urticaria, rosacea, alopecia areata),
      sideropenic anemia, growth retardation, late menarche, extragastric MALT
      lymphoma, diabetes mellitus, hepatic encephalopathy, sudden infant death
      syndrome, and anorexia of aging. We examine critically the strength of the
      evidence linking these diseases to Helicobacter pylori, using ischaemic heart
      disease as an example of epidemiological techniques, and skin diseases as an
      example of treatment studies. By the standards of evidence-based medicine,
      studies have been often of low quality. The best evidence usually is not
      indicative of a role for Helicobacter pylori in these diseases.

PMID- 11233524
TI  - Helicobacter in extragastric intestinal and liver disease.

PMID- 11233525
TI  - The long-term consequences of endoscopic sphincterotomy.

PMID- 11233526
TI  - Idiopathic colonic varices: an unusual cause of massive lower gastrointestinal
      hemorrhage.
AB  - Varices of the entire colon are very rare. This rare cause of massive lower
      gastrointestinal hemorrhage is almost invariably associated with cirrhosis of the
      liver and consequent hypertension or portal venous obstruction. We report about a
      patient with massive lower gastrointestinal bleeding from extensive colonic
      varices. Despite extensive investigation and a follow-up of 3 years, the etiology
      of the colonic varices could not be determined. Only a few cases of apparent
      idiopathic (familial or non-familial) colonic varices have been described.
      Recognition of this abnormality is important, however, because colonic varices
      may be the cause of recurrent, frequently massive lower gastrointestinal
      hemorrhage. A misleading endoscopic diagnosis can lead to inappropriate biopsies,
      resulting in major bleeding.

PMID- 11233527
TI  - Genotype and phenotype in paediatric endocrine practice.

PMID- 11233528
TI  - Lessons in labour.

PMID- 11233529
TI  - Regulatory peptides: what do they regulate?

PMID- 11233531
TI  - The global challenge.

PMID- 11233532
TI  - Cities at the forefront.

PMID- 11233530
TI  - NF-AT5: the NF-AT family of transcription factors expands in a new direction.

PMID- 11233533
TI  - Freshwater: lifeblood of the planet.

PMID- 11233534
TI  - Oceans in decline.

PMID- 11233535
TI  - Global warming: worrisome signs.

PMID- 11233536
TI  - Forests--the earth's lungs.

PMID- 11233537
TI  - Endangered biodiversity.

PMID- 11233539
TI  - An agenda for change.

PMID- 11233538
TI  - Toward a livable future.

PMID- 11233540
TI  - The earth and its people.

PMID- 11233541
TI  - Pollution and health risks.

PMID- 11233542
TI  - Feeding a future world.

PMID- 11233543
TI  - Nuclear medicine in tailoring treatment in oncology.

PMID- 11233544
TI  - In vitro adsorption of 99Tc(m)-MIBI, 99Tc(m)-tetrofosmin, 99Tc(m)-furifosmin and
      99Tc(m)O4- onto tubes.
AB  - Adsorption of radiopharmaceuticals onto disposable syringes has been reported to
      amount to levels of almost 50%. Data on adsorption of radiopharmaceuticals onto
      materials used for in vitro studies are extremely limited. We assessed the extent
      of adsorption of 99Tc(m) hexakis(2-methoxyisobutylisonitrile) (99Tc(m)-MIBI),
      99Tc(m)-tetrofosmin, 99Tc(m)-furifosmin and 99Tc(m)O4 onto tubes used for in
      vitro measurement of cellular uptake of these radiopharmaceuticals. The influence
      on adsorption of different incubation media, temperature and time of incubation
      was evaluated. Total (not corrected for adsorption) uptake was compared with
      corrected, net cellular uptake in SK-BR-3, MCF-7 and liposarcoma cell lines.
      Values of adsorption ranging from 0.94+/-0.13% to 7.07+/-0.46% were found. The
      extent of adsorption of all the radiopharmaceuticals varied with the type of
      incubation medium and the incubation temperature. With 99Tc(m)-furifosmin,
      adsorption was dependent on the incubation time as well on the incubation
      temperature and some of the incubation media investigated. Our findings indicate
      that systematic investigations to evaluate the adsorption of radiopharmaceuticals
      onto materials used during in vitro studies of cellular uptake should be
      considered a mandatory aspect of quality control.

PMID- 11233545
TI  - 99Tc(m)-MAG3: problems with radiochemical purity testing.

PMID- 11233546
TI  - Robustness of slope-intercept versus slope-only for measurement of glomerular
      filtration rate.

PMID- 11233547
TI  - Sentinel lymph node biopsy in breast cancer patients: subdermal versus
      peritumoural radiocolloid injection.
AB  - BACKGROUND AND AIMS: Sentinel lymph node (SLN) biopsy has been widely used in the
      management of melanoma and breast cancer. The aims of this study were (1) to
      compare the results obtained with the two main injection techniques, the
      peritumoural and subdermal; and (2) to determine the reliability of SLN to
      predict the regional lymph node status. METHOD: We prospectively studied 80 women
      (mean age 56 years) with breast cancer. Thirty-four of them were T1 and the
      remaining 46 were T2. Patients were divided into two groups. Group A, 36 patients
      were injected subdermally, surrounding the tumour site. Group B, 44 patients were
      injected peritumourally guided by ultrasound if non-palpable. Planar images were
      performed 15 min after the injection and continued until SLN identification.
      Before surgery, blue dye injection was administered similarly to the
      radiocolloid. After incision, a hand-held gamma probe was used to reach the SLN.
      All nodes harvested were analysed by classic pathology techniques. RESULTS:
      Overall, lymphoscintigraphy allowed the detection of SLN in 75/80 patients (94%).
      All subdermal lymphoscintigraphies were positive (36/36) compared with 89% of
      peritumoural (39/44). Blue dye detected SLN in 23/31 patients (74%) after
      subdermal injection and in 24/34 patients (71%) after peritumoural injection. The
      sensitivity to localize the SLN with lymphoscintigraphy+blue dye+gamma probe was
      92% (33/36) within the subdermal group and 91% (40/44) within the peritumoural
      group. Overall, five false negative SLN were found. All of these corresponded to
      T2 tumours with a size greater than 2.5 cm. The negative predictive value and the
      accuracy were 93% and 94%, respectively, for the subdermal group and 90% and 93%
      for the peritumoural group. CONCLUSIONS: (1) Our results indicate that both
      techniques have similar results. However, we suggest that T2 tumours with a size
      greater than 2.5 cm should be excluded from the SLN technique, in order to
      improve the accuracy and negative predictive value. (2) Lymphoscintigraphy is
      essential for visualizing the SLN, and blue dye can be helpful when the gamma
      probe does not localize the SLN.

PMID- 11233548
TI  - Non-visualization of sentinel lymph node in patients with breast cancer.
AB  - Histological evaluation of the first draining lymph node (sentinel node) in the
      axilla of patients with breast cancer has dramatically altered the surgical
      approach to these patients, with sparing of the axilla if no tumour cells are
      identified. In a fraction of patients imaged after peri-tumoural injection of the
      breast, there is no visualization of the sentinel node. We retrospectively
      analysed the status of patients whose nodes were visualized and of patients whose
      nodes failed to visualize, to define the variables associated with non
      visualization of the sentinel node. Seventy-four breast cancer patients were
      imaged following peri-tumoural injection of filtered 99Tc(m)-sulfur colloid,
      immediately and up to 5.5 h post-injection. The scintigraphic data were analysed
      with reference to the patient's age, histology, grade, site and size of tumour,
      previous diagnostic procedure and time interval to scan, using univariate
      analysis and a logistic regression model. A sentinel node was visualized in 53 of
      74 women (72%). Comparison of patients with non-visualized versus visualized
      sentinel nodes disclosed no statistically significant univariate relation to age
      of the patients (P = 0.10), size of tumour (P = 0.46), site (P = 0.26), histology
      [invasive ductal carcinoma in 16 of 20 (80%) non-visualized cases, and in 43 of
      53 (81%) visualized patients], prior excision biopsy (P = 0.36) and time interval
      to surgery (P = 0.29). Tumour grade was the only significant variable on
      univariate analysis (P = 0.03), though multivariate analysis showed that none of
      the independent parameters were statistically significant. In 39 patients with an
      upper outer quadrant tumour, the location of the sentinel node was not limited to
      the axilla and even crossed the midline of the breast. Our results show that none
      of the independent variables is associated with non-visualization of sentinel
      lymph node on preoperative lymphoscintigraphy of patients with breast cancer,
      though the tumour grade may have contributed to non-visualization of this node.
      The non-axillary drainage from upper outer quadrant tumours suggests the routine
      use of lymphoscintigraphy prior to axillary dissection.

PMID- 11233549
TI  - Detection of head and neck cancer with 99Tc(m) glutathione: a correlative study
      with tissue glutathione and glutathione S-transferase levels.
AB  - In this study glutathione (GSH), a natural tripeptide which plays an important
      role in detoxification reactions, protecting cells against damage from
      xenobiotics, has been labelled with 99Tc(m) for the demonstration of head and
      neck cancer. Twenty-eight patients (10 females and 18 males) with various
      malignancies of the head and neck were given 740 MBq of 99Tc(m)-GSH intravenously
      and single-photon emission computed tomography (SPECT) images were obtained at 3
      h. Semiquantification was performed by drawing regions of interest on three
      consecutive transaxial slices and tumour to background ratios were calculated. In
      addition, GSH and glutathione S-transferase (GST) levels were measured in the
      tumour samples and in normal tissue which were obtained during surgery.
      Scintigraphic images showed that there was increased uptake in the tumour
      compared to the normal contralateral side (tumour/normal tissue (mean +/- SD) =
      1.94 +/- 0.76). The tissue analyses revealed increased levels of GST in tumour
      tissues, but both GST and GSH levels in tumour were not statistically different
      from those in the normal tissue. We conclude that scintigraphic visualization of
      head and neck tumours can be attributed to increased demand for GSH in cancer.
      Protein binding might account for the prolonged retention of 99Tc(m)-GSH in the
      malignant tissue. Like other peptides, it is accumulated and excreted by the
      kidneys, which allows clear visualization of the abdomen without interference
      from gastrointestinal system activity.

PMID- 11233550
TI  - The relationship between 99Tc(m)-sestamibi uptake and ultrastructural cell types
      of thyroid tumours.
AB  - Although several hypotheses have been suggested regarding the accumulation of
      99Tc(m)-sestamibi in tumours, the exact uptake mechanism is still a matter of
      discussion. We investigated ultrastructural cell type of thyroid tumours by
      electron microscopy (EM) and compared them with uptake of 99Tc(m)-sestamibi.
      Thyroid scintigraphy with 99Tc(m)-sestamibi was performed on 25 patients who
      displayed a cold nodule on previous pertechnetate scintigraphy. Tumour-to-thyroid
      (T/N) uptake ratio was measured semiquantitatively. Surgery was performed in all
      patients and cytological evaluations were done by EM. Histopathology revealed six
      papillary carcinomas, 16 follicular adenomas and three Hurthle cell tumours.
      Thyroid cells were classified as A and B cells using EM. The cytoplasm of an A
      cell has the normal amount of mitochondria, whereas cytoplasm of a B cell
      (mitochondria-rich oxyphilic cell) contains abundant mitochondria. The median T/N
      ratio on the early scan for an A-cell tumour was 1.21 (range, 0.74-3.2), late T/N
      ratio was 1.25 (range, 0.72-3.85). The T/N ratio for the B-cell tumours was 1.42
      (range, 0.6-3.6) on the early scan and 1.18 (range, 0.64-5.58) on the late scan.
      There was no statistically significant difference between T/N ratios of A- and B
      cell tumour groups. A significant difference was also not seen between early and
      late T/N ratios. According to our findings, 99Tc(m)-sestamibi accumulates in
      thyroid tumours with both A and B cells, therefore these results suggest that the
      mitochondrial content of tumours is not only responsible for sestamibi uptake and
      retention.

PMID- 11233551
TI  - The additive value of gated SPET myocardial perfusion imaging in patients with
      known and suspected coronary artery disease.
AB  - In myocardial perfusion scintigraphy, the clinical significance of fixed defects
      presents some difficulty. In this study, we evaluated whether additional
      information on left ventricular function assessed by quantitative gated single
      photon emission computed tomography (gated SPET) would increase the diagnostic
      yield of the study in such patients. We studied 55 patients with a previous
      myocardial infarction and 20 patients without a previous myocardial infarction
      using gated SPET 99Tc(m)-tetrofosmin myocardial perfusion imaging. Each patient
      had to have a persistent perfusion defect consisting of at least three contiguous
      segments in the same vascular territory. The left ventricle was divided into 20
      segments which were analysed for perfusion and wall thickening on a 4-point
      severity scale. Of the 55 patients with myocardial infarction, 19 (35%) patients
      showed preserved wall thickening in the region of the previous infarction with
      fixed perfusion abnormalities, which suggested residual myocardial viability. In
      the 20 patients without myocardial infarction, preserved wall thickening was seen
      in 10 (50%) patients with fixed perfusion defects, suggesting an attenuation
      artefact. Conversely, in 16 (29%) patients in the myocardial infarction group and
      two (10%) patients in the non-myocardial infarction group normal perfusion was
      associated with severely diminished wall thickening possibly due to stunning. We
      found an excellent correlation between wall thickening and left ventricular
      ejection fraction both for the patients with myocardial infarction and the
      patients without myocardial infarction (r = 0.86 and r = 0.82, respectively, both
      P<0.0001). A reasonable correlation between perfusion and left ventricular
      ejection fraction was found for the patients with myocardial infarction (r =
      0.41, P = 0.002), and a non-significant correlation for the patients without
      myocardial infarction (r = 0.37, P = 0.1). Quantitative gated SPET myocardial
      imaging allows the detection of residual wall thickening in patients with a
      previous myocardial infarction who show severe fixed perfusion defects. In
      patients without myocardial infarction, gated SPET imaging allows differentiation
      between an attenuation artefact and a fixed perfusion defect due to coronary
      artery disease. In addition, gated SPET may show diminished ventricular function
      in normally perfused segments possibly due to myocardial stunning. The addition
      of gated SPET myocardial perfusion imaging increases diagnostic confidence and
      may have direct clinical implications for optimal patient management.

PMID- 11233552
TI  - Is there a role for agonist gastrin-releasing peptide receptor radioligands in
      tumour imaging?
AB  - Gastrin-releasing peptide (GRP) has been shown to be a tumour growth stimulating
      agent for a number of normal and human cancer cell lines. The tumour growth
      effect is a direct result of GRP binding to membrane G-protein coupled GRP
      receptors (GRP-R) on the cell surface. Available data on the role of GRP and GRP
      R in human lung, prostate, breast, colorectal and gastric carcinoma are reviewed
      and it is suggested that radiolabelled agonists are preferable to antagonists for
      imaging and therapy as they appear to be internalised, yielding a higher
      target/background ratio. The use of rhenium or indium radiolabels for therapy may
      provide a new approach to GRP/bombesin expressing tumours.

PMID- 11233553
TI  - Thallium gated SPECT: relation between immediate post-stress evolution of
      ejection fraction and severity of perfusion pattern.
AB  - BACKGROUND AND AIMS: A significant decrease of left ventricular ejection fraction
      (LVEF) at stress has been reported with 99Tc(m) gated single-photon emission
      computed tomography (gSPECT) in severe myocardial stunning up to 1 h after
      exercise. This study was designed to show whether 201Tl gSPECT can measure LVEF
      evolution from rest to stress in routine examination and give additional
      information to perfusion interpretation since acquisition starts immediately
      after stress test. METHODS: Post-exercise and rest 201Tl gSPECT were performed in
      187 patients with suspected coronary artery disease. Myocardial perfusion was
      quantified by 20-segment analysis. Patients were divided into four groups
      according to their summed perfusion score, reversibility rate and
      electrocardiographic findings, i.e. in order of severity: I = normal perfusion,
      II = fixed defect owing to a myocardial infarction, III = full reversible
      ischaemia, and IV = partial reversible ischaemia. LVEF was calculated by
      Germano's automatic algorithm. RESULTS: Normal subjects (n = 29) and infarcted
      patients (n = 34) showed a significant LVEF increase between rest and stress, +7
      +/- 9% and +5 +/- 7% respectively. In full reversible ischaemic patients (n =
      46), stress LVEF showed no increase (+1 +/- 8%) and this group was statistically
      different from both group I and group II. Furthermore, when ischaemia was
      partially reversible (n = 31), LVEF decreased significantly (-3 +/- 8%),
      particularly when exercise tests were abnormal (-4 +/- 8%). Group IV was
      statistically different from groups I and II. CONCLUSIONS: Good agreement exists
      between the severity of ischaemic perfusion pattern and LVEF degradation at
      stress, which is consistent with previously published data using 99Tc(m) gSPECT.
      Additionally, the use of 201Tl for immediate post-exercise imaging allows the
      observation of a physiological LVEF increase in normal and infarcted patients.

PMID- 11233554
TI  - Enhanced 99Tc(m)-MIBI SPECT detection of hibernating myocardium following the use
      of sub-lingual nitroglycerine.
AB  - The purpose of this study was to assess the feasibility of detecting hibernating
      myocardium using 99Tc(m)-MIBI SPECT imaging following the use of sublingual
      glyceryl trinitrate (GTN). Thirty-eight subjects were studied, five asymptomatic
      and 33 with a history of myocardial ischaemia or myocardial infarction (MI). The
      study was conducted on two separate days, both at rest, one under controlled
      basal conditions and the other 20 min following the sublingual administration of
      GTN. A total of 190 cardiac segments were qualitatively analysed and 72 segments
      with fixed defects were compared to the study following the use of GTN for
      evidence of improved radionuclide uptake. Following GTN, 73.6% of fixed segment
      defects showed no change in uptake, 5.5% showed probable improvement whilst in
      20.8% a definite enhanced uptake was demonstrated. In 3.7% of segments, worsening
      of radionuclide uptake was observed.

PMID- 11233555
TI  - Scintigraphic assessment of the acetabulum after arthroplasty with reference to
      cup geometry.
AB  - A unique scintigraphic appearance has been noted in uncomplicated hip prostheses
      which have the acetabular component inserted after under-reaming or where a cone
      shaped cup is inserted. We hypothesized that the pattern of increased uptake
      around the superior and inferior third of the cup with relatively reduced uptake
      in the medial third is due to preferential loading of the rim of the cup. A
      prospective study of ten patients with uncomplicated hip prostheses supports the
      hypothesis.

PMID- 11233556
TI  - Radiation exposure from patients treated with 165Dy-ferric hydroxide.
AB  - In radiation synovectomy about 10 GBq 165Dy-ferric hydroxide is injected into
      major joints. Measurements of the dose rates were performed at distances of 5 cm,
      0.5 m, 1 m and 2 m from the surface of the treated joints (knees) until 200 min
      after the application in 16 patients in order to estimate the radiation exposure
      of persons in the neighbourhood of the patients. The highest doses were estimated
      for the fingers of the technologist (320 microSv) and for the physician (700
      microSv). Special shields for the syringes were constructed for dose reduction.
      The whole-body doses were 103 microSv for the technologist and 40 microSv for the
      physician. After the discharge of the patient to a ward or home, other persons at
      1 m distance from the patient might receive 88 microSv, which is less than 9% of
      the annual permissible dose. Our results clearly demonstrate that the calculated
      radiation exposure to personnel and family members is well below the maximum
      annual dose limit for non-professionally exposed persons.

PMID- 11233557
TI  - European rules governing radiopharmaceuticals as medicinal products for human use
      in the EU.
AB  - The development of EU legislation affecting radiopharmaceuticals is reviewed. The
      requirements for the preparation of a Summary of Product Characteristics are set
      out. It is concluded that, across the Community, there is wide variation in the
      effectiveness of implementation of the regulations.

PMID- 11233558
TI  - Uptake mechanisms of L-3-[125I]iodo-alpha-methyl-tyrosine in a human small-cell
      lung cancer cell line: comparison with L-1.
AB  - The radiolabelled amino acid analogue L-3-[125I]iodo-alpha-methyl-tyrosine (IMT)
      is under evaluation in brain tumours, where it reflects amino acid transport
      activity, but is also taken up in many other tumour types. This study
      investigated the uptake mechanism of IMT in tumour cells not derived from brain
      tumours, in comparison with the native amino acid 14C-tyrosine (Tyr) from which
      IMT is derived. Human GLC4 small-cell lung cancer cells in log-phase were
      incubated with IMT and Tyr. Tracer uptake was determined in various buffers,
      incubation periods, concentrations of specific amino acid transport blockers, pH
      and temperature. IMT uptake was very fast, reaching a plateau within 5 min, while
      Tyr kept on accumulating for > 60 min. Based on steady-state experiments, > 90%
      of IMT uptake could be attributed to amino acid transport activity. The L
      transport system was the most important, both for IMT and Tyr. IMT uptake into
      GLC4 tumour cells is almost completely the result of amino acid transport
      activity (especially the L system) and is very similar to Tyr uptake. Therefore,
      also outside the brain, IMT is a metabolic tracer that may reflect the increased
      amino acid transport that is characteristic for malignant tumours.

PMID- 11233560
TI  - Detection of irradiated spices by different physical techniques.
AB  - We used thermoluminescence, electron spin resonance, and viscosimetric
      measurements to establish whether or not a spice had been irradiated.
      Thermoluminescence, using the 1788 EN official protocol with an alternative
      method for the extraction of mineral impurities, led to proof of irradiation or
      proof of no treatment. Electron spin resonance led to different spectrum shapes
      depending on the chemical composition of the spices; ESR could only be used as
      proof of irradiation up to several weeks after irradiation, and only for some
      spices. Viscosimetric measurements carried out on spice suspensions led to a
      presumption of treatment (or of no treatment) and possibly to proof of
      irradiation.

PMID- 11233559
TI  - Potential 166Ho radiopharmaceuticals for endovascular radionuclide therapy. II.
      Preparation and evaluation of 166Ho-DTPA.
AB  - 166Ho, with its favourable radiation characteristics of t(1/2) 26.8 h and Ebeta
      1.85 and 1.75 MeV, is proposed as a suitable choice for the endovascular
      radionuclide therapy (EVRT) technique of liquid filled, low pressure balloon
      angioplasty. 166Ho was produced by the (n,gamma) reaction on a natural Ho2O3
      target. The specific activity obtained was approximately 100 mCi x mg(-1) when
      irradiated at a flux of 2 x 10(13) n x cm(-2) s(-1) for approximately 7 days, and
      the possible contaminant 166Ho(m) was not detected. 166Ho was easily complexed
      with diethylenetriaminepentaacetic acid (DTPA) at a ligand to metal molar ratio
      ([L]:[M]) of 1:1 at room temperature (22-23 degrees C) and a reaction time of a
      few minutes. The radiochemical purity was >99%, as determined by paper
      chromatography using a mixture of pyridine, ethanol and water (1:2:4) as solvent.
      The complex had good stability up to 72 h at 37 degrees C in a serum environment.
      In a study using Swiss mice > 85% of the injected dose was cleared into the urine
      within 30 min post-injection, with insignificant retention in any major tissues.
      The studies show that the 166Ho-DTPA complex could be an alternative to the more
      expensive and difficult to access 188Re based products for EVRT, and provide
      adequate uniform radiation dose for the arterial vessel wall under treatment.

PMID- 11233561
TI  - A comparison of the kinetics of low-density lipoprotein oxidation induced by
      copper or by gamma-rays: influence of radiation dose-rate and copper
      concentration.
AB  - The oxidation of low-density lipoproteins is the first step in the complex
      process leading to atherosclerosis. The aim of our study was to compare the
      kinetics of low density lipoprotein oxidation induced by copper ions or by oxygen
      free radicals generated by 60Co gamma-rays. The effects of copper concentration
      and irradiation dose-rate on LDL peroxidation kinetics were also studied. The
      oxidation of LDL was followed by the measurement of conjugated diene,
      hydroperoxides, and thiobarbituric acid reactive substance formation as well as
      alpha-tocopherol disappearance. In the case of gamma irradiation, the lag-phase
      before the onset of lipid peroxidation was inversely correlated to the radiation
      dose-rate. The radiation chemical rates (nu) increased with increasing dose-rate.
      Copper-induced LDL peroxidation followed two kinetic patterns: a slow kinetic for
      copper concentrations between 5-20 microM, and a fast kinetic for a copper
      concentration of 40 microM. The concentration-dependent oxidation kinetics
      suggest the existence of a saturable copper binding site on apo-B. When compared
      with gamma-rays, copper ions act as drastic and powerful oxidants only at higher
      concentrations (> or = 40 microM).

PMID- 11233562
TI  - Behavioural consequences of an 8 Gy total body irradiation in mice: regulation by
      interleukin-4.
AB  - The effects of an 8 Gy gamma total body irradiation (TBI) on exploration and
      locomotion activities as well as temperature were studied in C57BL6/J mice.
      Survival, body weight, and blood cell counts were also assessed in irradiated
      mice treated with placebo or interleukin (IL)-4. The efficacy of IL-4 treatment
      on improvement in exploration activity was evaluated. The study was carried out
      from 3 h to 30 days following exposure. Our results showed a biphasic response to
      irradiation concerning the exploration activity of mice. Irradiated mice had
      reduced activity as early as 3 h after exposure, with recovery of activity within
      24 h. The exploration activity again decreased 4 days after irradiation and the
      recovery occurred slowly after day 17. IL-4 ameliorated the exploration status in
      mice in both phases. The locomotion activity was studied using a telemetry
      apparatus. A similar pattern to that of the exploration data was observed, with a
      minimal activity observed between days 13 and 17. A radiation-induced hypothermia
      was also noticed over the same time period.

PMID- 11233563
TI  - Gamma radiation effects on alpha-lactalbumin: structural modifications.
AB  - Alpha-lactalbumin was irradiated in the lyophilized state in air at ambient
      temperature. The irradiated protein was examined by size exclusion
      chromatography, sodium dodecyl sulfate polyacrylamide gel electrophoresis,
      circular dichroism, and microcalorimetry. Irradiation induced the loss of
      aromatic amino acids and of helicity so that fragmentation and aggregation
      products were obtained. The thermodynamic properties of the protein were also
      modified. The irradiated protein had lower stability, however, the temperature at
      which denaturation occurred process remained constant.

PMID- 11233565
TI  - Sulfur-centered reactive intermediates derived from the oxidation of sulfur
      compounds of biological interest.
AB  - Sulphur compounds play a central role in the structure and activity of many vital
      systems. In the living cell, sulfur constitutes an essential part of the defense
      against oxidative damage and is transformed into a variety of sulfur free radical
      species. Many studies of the chemistry of sulfur-centered radicals using pulse
      radiolysis and photolysis techniques to detect and measure the kinetics of these
      radicals have been published and reviewed. This paper discusses the present state
      of research on the formation and reactivity of certain sulfur-centered radicals
      [RS*, RSS*, RS*+, (RSSR)*+] and their implications for biological systems.

PMID- 11233566
TI  - Radiation induced peroxidation of polyunsaturated fatty acids: recent results on
      formation of hydroperoxides.
AB  - Aqueous solutions of linoleic acid were irradiated in air with gamma-rays of
      137Cs. High pressure liquid chromatography (HPLC) was been used to separate and
      measure the production of hydroperoxides. The results obtained after reverse
      phase chromatography, associated with a microperoxydase for hydroperoxide
      detection, indicate the presence of two different hydroperoxides. One type of
      hydroperoxide was the major product obtained when the initial linoleic
      concentrations were below the critical micellar concentration (2 mM), and the
      second type was produced when the concentrations were above 2 mM. A further
      separation carried out on the second hydroperoxide by direct phase HPLC showed
      that it contains three compounds, mainly HPODE 9 and 13.

PMID- 11233567
TI  - Recoil proton, alpha particle, and heavy ion impacts on microdosimetry and RBE of
      fast neutrons: analysis of kerma spectra calculated by Monte Carlo simulation.
AB  - Fast neutrons (FN) have a higher radio-biological effectiveness (RBE) compared
      with photons, however the mechanism of this increase remains a controversial
      issue. RBE variations are seen among various FN facilities and at the same
      facility when different tissue depths or thicknesses of hardening filters are
      used. These variations lead to uncertainties in dose reporting as well as in the
      comparisons of clinical results. Besides radiobiology and microdosimetry, another
      powerful method for the characterization of FN beams is the calculation of total
      proton and heavy ion kerma spectra. FLUKA and MCNP Monte Carlo code were used to
      simulate these kerma spectra following a set of microdosimetry measurements
      performed at the National Accelerator Centre. The calculated spectra confirmed
      major classical statements: RBE increase is linked to both slow energy protons
      and alpha particles yielded by (n,alpha) reactions on carbon and oxygen nuclei.
      The slow energy protons are produced by neutrons having an energy between 10 keV
      and 10 MeV, while the alpha particles are produced by neutrons having an energy
      between 10 keV and 15 MeV. Looking at the heavy ion kerma from <15 MeV and the
      proton kerma from neutrons <10 MeV, it is possible to anticipate y* and RBE
      trends.

PMID- 11233564
TI  - Fourier-transform infrared spectroscopy: a pharmacotoxicologic tool for in vivo
      monitoring radical aggression.
AB  - Among the physico-chemical methods that can be used to investigate induced
      peroxidation in living cells, Fourier transform infrared (FT-IR) spectroscopy
      appears to be a valuable technique as it is non-destructive and sensitive for
      monitoring changes in the vibrational spectra of samples. We examined microsomal
      fractions from rat liver and brain by FT-IR to study the effect of radical
      aggression induced in vivo by carbon tetrachloride (CCl4). The length of the acyl
      chains was increased as a consequence of peroxidation induced by the xenobiotic.
      Moreover, an enhanced level of cholesterol esters and an increase in
      phospholipids were observed in the liver and the brain, respectively. The
      conformational structure of the membrane proteins was changed in both the liver
      and the brain. In the polysaccharide region, we observed an important loss in
      glucidic structures, such as a decrease in liver glycogen and in some brain
      glycolipids. These alterations are probably due to the interactions between cells
      and CCl4 and the metabolic changes caused by CCl4. Thus, FT-IR spectroscopy
      appears to be an useful tool and an accurate means for rapidly investigating the
      in vivo biochemical alterations induced by CCl4 in microsomes, and for
      correlating them with biochemical and physiological data.

PMID- 11233568
TI  - Enhanced strand break induction of DNA by resonant metal-innershell
      photoabsorption.
AB  - We determined the number of single and double strand breaks (ssb and dsb) in a
      DNA-chloroterpyridine platinum complex induced by resonant photoabsorption in the
      L(III) innershell of a platinum atom. The number of ssb and dsb were measured in
      supercoiled plasmids (AG30) versus the chloroterpyridine platinum concentration,
      i.e., the ratio of intercalated molecules to the number of phosphate sites in
      DNA. A significant increase in the number of ssb and dsb was observed when the
      DNA contained intercalated molecules. This technique is an efficient way to
      induce ssb and dsb triggered by the atomic Auger effect.

PMID- 11233569
TI  - ["Dear Kitty, you asked me...": imaginary companions and real friends in
      adolescence].
AB  - Based on semistructured interviews and the analyses of diary entries, frequency
      and function of imaginary companions, compared to real friendships, were
      investigated in an adolescent sample. Results suggest that while imaginary
      companions fulfill a number of different functions for the identity development,
      which supplement experiences with close friends, they do not compensate for the
      lack of close friendships. Real and fantasized comparisons with a highly similar
      significant other are most important. Interestingly, as an adult, writers hardly
      remember these positive functions for their own developmental progression.

PMID- 11233570
TI  - [Characteristics of communication of schizophrenic, neurotic, and healthy
      adolescents].
AB  - Research on communication skills in psychotic patients demonstrates that in
      dialogues schizophrenics neglect the needs of the listener. There are only few
      linguistic studies which investigate the speech of schizophrenic children and
      adolescents. The verbal and non-verbal communication of schizophrenic, neurotic,
      and healthy adolescents during a problem solving situation was transcribed and
      compared by a content analysis. The transcripts were screened for dialogue
      control and communication disturbance of verbal/non-verbal activities of the
      speaker and listener: Dialogue control was defined by the variables signals of
      the speaker or signals of hearer and eye or body contact of the test person to
      the experimenter. Communication disturbance was defined as the amount of
      incomprehensible articulation and selections. Neurotic test persons produce the
      highest signals of speaker rate. In dialogues with neurotic and schizophrenic
      test persons the experimenter uses more signals of hearer than in dialogues with
      healthy test persons. In dialogues with neurotic test persons the experimenter
      shows more signals of the speaker than in dialogues with healthy test persons.
      Schizophrenics neglect more often the statements of the experimenter than in
      other dialogues and vice versa. Although the experimenter was instructed to
      restricted verbal behavior the communication intensified in the neurotic group.
      The communication in the schizophrenic group was characterized by frequent
      communication disturbance.

PMID- 11233571
TI  - [Day treatment in German child and adolescent psychiatry: analysis of data from a
      nationwide survey with respect to cost effectiveness].
AB  - Day treatment plays an increasingly important role in German child and adolescent
      psychiatry. In spite of a steady and ongoing increase of day treatment facilities
      over the past 15 years only few empicial data on the structure of German day
      treatment are available. The study refers to an Germany wide assessment of all
      day treatment centers (DTC). 45 out of 61 DTC responded (reply rate 74%).
      Analyses were done over 560 treatment places used by 69% male and 31% female
      patients mean ages 10 years and 2 months. Mean treatment duration is 104 days
      without differences with respect to the primary psychotherapeutic orientation
      (behavioral, psychodynamic, family therapy, other). Personnel is in 80.5% of the
      DTC below the governmental guidelines. Rates per day vary between 280 DM and 617
      DM with a mean of 389 DM. Mean treatment costs per patient are 36.303 DM (min.:
      12.825 DM; max.: 89.793 DM). Rates per day and duration of treatment are
      negatively correlated: The higher the rate per day, the shorter the treatment
      (explained variance: 17%). This correlation can only be explained indirectly by
      more personnel as associated with higher daily rates. However, more influential
      is the amount of time the children are present in day treatment per week: The
      longer the children are present, the shorter the duration of the whole treatment.
      Diagnosis, gender, and age only influence duration and costs of the treatment
      marginally. Network-effects as operationalized by the availability of additional
      inpatient and outpatient facilities did not influence costs and duration of day
      treatment.

PMID- 11233572
TI  - [Guilt and subjective feelings of guilt in the context of separation and
      divorce].
AB  - In this paper the vicissitudes of guilt and responsibility and development and
      function of guilt feelings are discussed in the context of the typical family
      dynamics in cases of divorce (delegation, claiming of loyalty, parentification).
      The "guilt" of the parents is often transformed to the feeling of guilt of the
      children in the sense of a traumatic feeling of guilt. This happens especially
      when sufficient mourning is not possible. Feelings of guilt by reason of the mere
      existence of the child (basic feelings of guilt) and the oedipal and other
      feelings of guilt out of rivalry can be reinforced (feelings of guilt out of
      vitality). Strivings for separation may be connected with guilt by the children
      (feelings of guilt regarding separation). The recognition of the adults'
      responsibility (especially choice of partners, functionalization of the child to
      facilitate the separation from the own parents, to maintain the image of an
      intact family or the struggle for power at the cost of the children) diminishes
      the feelings of guilt of the children.

PMID- 11233573
TI  - [Health promotion in the occupational setting: what are the prospects in the
      Italian situation?].
AB  - Over the past decades advances in sciences and medicine have improved living and
      health conditions and lengthened life expectancy. These benefits are associated
      with an increase in prevalence of chronic degenerative diseases. With their multi
      factorial aetiology these diseases are influenced by life styles and personal
      habits and require prolonged medical care and high social costs. Now days health
      is no longer considered as the absence of disease but a state of mental, physical
      and social well-being. The World Health Organization has defined health promotion
      as "the process of enabling people to increase control over and to improve
      health". Since the 70s in the USA many health promotion programmes have been
      proposed, especially by large corporations, in order to ensure a more efficient,
      productive and motivated work-force, to reduce health insurance costs and to
      provide a better company image. Workplaces,--particularly when the working
      population is relatively stable--are excellent areas for health promotion
      programmes because workers can be monitored over a long period of time. The most
      successful programmes are aimed at modifying behaviour in risk patterns (smoking,
      alcohol abuse, eating disorders, etc.) through information, active participation,
      screening, follow-up, personalized programmes, changes in the working
      environment, physical exercise programmes. These health promotion programmes are
      extremely hard to develop for Italian workers. Most firms are small or very small
      and much still remains to be done to eliminate well-known occupational risk
      factors. The current flexibility of modern work patterns could constitute a
      further obstacle.

PMID- 11233574
TI  - [Quality system and training of the occupational physician: a referral
      macromodel].
AB  - The progressive changes in society, in the working environment and in
      organization are leading to changes in the role of the occupational physician.
      This process requires a continuing renewal of the training curricula of the
      University Schools of Occupational Medicine. The revised curricula provide more
      appropriate guidance by setting learning objectives (knowledge an occupational
      physician should have in each formative area) and training objectives (experience
      an occupational physician should have). These changes require a new approach in
      delivering a successful teaching-learning service. A Quality System (QS) for
      training is a management tool aimed at identifying the training products required
      by the complex customer system (society, institutions, students, firms). A QS
      anticipates customers' needs and satisfies them; it guarantees the quality of the
      results by monitoring resources, activities and processes that directly influence
      the quality of the service/training product. The system is mainly based on the
      development and exploitation of the internal expertise and on the innovative
      approach by the customer-oriented structures. The system is also based on
      innovation of methods (methods of planning, delivering and evaluating) and on
      rationalization of the processes and the connected procedures of training tools,
      professional abilities, training and managerial documentation. Therefore,
      although all Specialization Schools share the same mission, i.e. training of the
      Specialist in occupational medicine, each School should adopt a Quality Policy in
      accordance with strategic choices made by the School in relation to its specific,
      history, values, perceived vision and situation of the market.

PMID- 11233575
TI  - [Malignant mesothelioma in the industrial area of Colleferro].
AB  - The study describes the occurrence of pleural and peritoneal malignant
      mesothelioma in the Colleferro industrial area (Province of Rome, 9
      municipalities, population 63,000, period 1993-98) which is the site of a large
      chemical plant (BPD) producing organic chemicals, acid mixtures, insecticides,
      explosives and dynamite, and was involved in manufacturing/maintenance of
      railroad rolling stock. Asbestos was extensively used in these plants in the
      past. Mesothelioma cases were actively searched from data in files of pathology
      archives, hospital admission and discharge (records), and death certificates
      recorded at local health authority register. 23 potential cases were identified
      for whom clinical charts and pathological slides were reviewed. A
      multidisciplinary evaluation of all collected information confirmed 18 cases of
      cyto-histologically proven malignant mesothelioma (pleural/peritoneal ratio of
      2.75:1) among residents and/or workers at BPD. The remaining 5 cases were defined
      as not mesothelioma; however, two were cases of lung cancer (both occupationally
      exposed to asbestos). All subjects with malignant mesothelioma had been
      occupationally exposed to asbestos (14 males and 3 females), except one (1 female
      with domestic exposure). No mesothelioma case was attributable to environmental
      exposure. Of the 17 cases with occupational asbestos exposure, 15 occurred in BPD
      workers employed in manufacturing/maintenance of railroad rolling stock (3
      cases), general maintenance services (5 cases), or in the armaments sector (7
      cases) and 2 in residents but not BPD workers (1 baker, 1 pipefitter). The
      incidence rate in residents of the 9 municipalities was 5.5 in males and 1.3 in
      females (standardized on the Italian population x100,000, census 1981). For
      Colleferro municipality only, the incidence was 10.1 in males and 4.1 in females,
      which are the highest rates reported so far in Italy. Besides confirming the risk
      of mesothelioma risk in railroad rolling stock manufacturing and asbestos
      insulated pipe maintenance workers, this study identifies a cluster of malignant
      mesothelioma in explosives production workers.

PMID- 11233576
TI  - [A "technically attainable" refernce value for exposure to wood dust in the light
      of Law 66/2000].
AB  - The question of appropriate exposure standards for wood dust is addressed by
      reference to the major health effects, especially sino-nasal cancer, that have
      been investigated. A review of several key papers on wood dust exposure permits
      some associations to be made between exposure data and effects, particularly
      impaired/suppressed nasal mucociliary clearance, according to which it may be
      suggested, based on available evidence, that a standard of 1.5-2 mg/m3 of total
      suspended wood dust could reasonably protect against the observed effects.
      Moreover, data from the literature show that reducing personal wood dust
      exposures to below 2 mg/m3 is accomplished relatively easily, whereas reducing
      exposures to below 1 mg/m3 is considerably more difficult and expensive. The
      exposure level of 1.5-2 mg/m3 is suggested for all wood dusts; it does not seem
      reasonable at the present time to distinguish between hardwood and softwood
      because many of the important mortality studies report results based on patients
      with mixed exposures. The threshold exposure value of 5 mg/m3 for hardwood
      proposed from 1/1/2003 by Law 66/2000 is deemed to be too high as a health-based
      occupational exposure limit.

PMID- 11233578
TI  - [Mobbing, considerations on a paradigm case].

PMID- 11233577
TI  - [Analysis of occupational exposure to asbestos in cases of mesothelioma
      registered in Romagna (1986-1998)].
AB  - The aim of this study was to evaluate the prevalence and major correlates of
      occupational exposure to asbestos among the 125 cases of mesothelioma of the
      pleura, peritoneum, and pericardium registered in the Romagna Region of Italy
      between 1986 and 1998. Adequate occupational information was obtained for 122
      (98%) cases. Among these, the male:female ratio was 81:41 (2.0), the median age
      was 68 years (range, 25-92), and the pleural location accounted for 96 (79%)
      cases. According to job history, 61 (50%) cases had had definite (23), probable
      (12), and possible (26) occupational exposure to asbestos. The probability
      (multiple logistic regression estimate) was greater for males (odds ratio, 10.8)
      but decreased for cases with mesothelioma of the peritoneum and pericardium
      (0.21) as well as those above the median age (0.38). Time period, residence, mode
      of diagnosis (histology, cytology, other), source of information (patient,
      wife/husband, others), and smoking habits exerted no independent effect. For 35
      (57%) cases, occupational exposure was related to asbestos pollution of the
      workplace and not to the specific work task. Cases with definite, probable, and
      possible occupational exposure showed no significant difference in the
      distribution (Kruskal-Wallis test) by year of initial employment at risk,
      duration of exposure, and latency (median, 36 years). Occupational exposure
      occurred in a total of 22 workplaces. Three of these accounted for 21 (34%)
      cases. Multiple (> or = 2) cases (total 27 or 44%) were observed in six
      workplaces.

PMID- 11233579
TI  - [Cultural problems and biases in the organization of preventive activities in the
      health business].

PMID- 11233580
TI  - Outbreak of Ebola haemorrhagic fever, Uganda, August 2000-January 2001.

PMID- 11233581
TI  - Measuring the physician perspective on quality of care in health plans.
AB  - Physicians provide one source of information about the quality of care in health
      plans, but concerns exist that physicians cannot distinguish quality from
      financial considerations or other underlying attitudes. We examined whether
      physicians can (a) distinguish different domains of health plan quality and (b)
      distinguish health plan quality from their underlying attitudes. We analyzed data
      on 419 generalist physicians from four health plans. Three scales assessed
      physicians' perceptions of facilitators and barriers to high-quality care in the
      plans and the clinical capabilities of plan physicians. Structural equation
      modeling indicated that physicians could distinguish domains of health plan
      quality. Physicians could also distinguish plan quality from their attitudes
      toward the plan, but plan quality was more highly correlated with general managed
      care attitudes than expected. These data suggest that physicians can provide
      information about health plan quality, but it will be important to validate these
      measures against patient outcomes.

PMID- 11233582
TI  - The effects of variations in mode of delivery and monetary incentive on
      physicians' responses to a mailed survey assessing STD practice patterns.
AB  - High response rates from physicians are key to obtaining valid and generalizable
      data regarding their sexually transmitted disease (STD) diagnosis, treatment, and
      control practices. A factorial (3 x 2) study was designed using varying cash
      incentives ($0, $15, $25) and delivery modes (Federal Express, U.S. mail).
      Surveys, with three follow-up mailings, were sent to a national probability
      sample of 311 physicians in OB-GYN, family practice, internal and emergency
      medicine, and pediatrics specialties. Overall, 156 physicians returned completed
      surveys (56% overall response rate). Significant effects for incentive level (F =
      28.2, df = 2, p < .01) and delivery mode (F = 4.1, df = 1, p < .05) existed.
      Highest response was among physicians in the $25-FedEx condition (81%). High
      response rates from busy practicing physicians can be achieved if surveys are
      relevant to clinical practice, sponsored by a reputable organization (the Centers
      for Disease Control and Prevention), include a monetary incentive, and are
      delivered by courier.

PMID- 11233583
TI  - Examining the generalizability of ratings across clerkships using a clinical
      evaluation form.
AB  - It is necessary to average multiple clinical evaluation form (CEF) observations
      to obtain a reliable score. Combining CEF observations across clerkships will
      provide more observations per student, but it is unknown how an across-clerkship
      generalization affects reliability. The authors conducted generalizability
      studies on balanced stratified random samples to examine the impact of averaging
      across clerkships. The study detected a student by clerkship interaction.
      Although the interaction magnitude was small, it had a large negative impact on
      the reliability of the mean score. The authors conclude that averaging across
      clerkships for the purpose of evaluating global clinical skills will produce a
      less reliable measure for a fixed number of observations than averages calculated
      within a clerkship for evaluating clerkship specific skills. The content
      specificity of clinical skills as measured by the CEF may resemble that found
      using other measurement methods.

PMID- 11233584
TI  - Cost-effectiveness of a lottery for increasing physicians' responses to a mail
      survey.
AB  - To evaluate the cost-effectiveness of a lottery on physicians' responses to a
      mail survey, a randomized controlled trial was conducted with a random sample of
      1,000 members of the Quebec Federation of General Practitioners in 1997. For the
      first mailing of this survey, each respondent was randomly assigned to the
      control or experimental group, which was offered participation in a lottery upon
      return of the questionnaire. Response rate was 41.2% in the experimental group
      and 34.8% in the control group, a 6.4% difference (CI95%: 0.6%-12.6%). The
      additional cost of the lottery was about Can$500, giving an incremental cost of
      Can$16 per questionnaire returned. In conclusion, a lottery resulted in a small
      but statistically significant increase in the response rate of physicians to a
      mail survey. This method may be a cost-effective option when applied to large
      surveys.

PMID- 11233585
TI  - Comparison of resident and medical student evaluation of faculty teaching.
AB  - Recognizing and rewarding teaching faculty are increasingly important to medical
      schools and are often hampered by low perceived reliability and validity of
      measures of teaching ability. The purpose of this study was to cross-validate two
      independently generated measures of teaching from medical students and residents.
      A total of 2,318 medical student and 4,425 resident scores for single-item
      measures of teaching ability for 129 teaching faculty members of a department of
      internal medicine over a 6-year period were compared. Results showed that average
      teaching scores were higher for medical students than residents. Rank order of
      faculty were within 2 quintiles for the two groups for over 90% of faculty.
      Highly discordant evaluations were seen for only 8% of faculty. The authors
      conclude the general concordance of two independent measures of teaching ability
      adds evidence to the existing literature of the validity of single-item measures
      of teaching ability from two different types of learners.

PMID- 11233586
TI  - The loss of student idealism in the 3rd-year clinical clerkships.
AB  - The purpose of this study was to specify how student attitudes toward different
      types of patients and the profession change during clinical rotations. A
      questionnaire was given to all medical students prior to 3rd-year rotations
      regarding their attitudes toward the medical profession and patient types. It was
      given again after students completed their 16-week medicine-surgery clerkship.
      Eighty-eight of 96 students responded to pre- and posttests. Students became less
      idealistic toward two patient groups: the elderly and people with chronic pain.
      After clerkship, students believed a greater percentage of the elderly were
      demented (26% increasing to 35%, p = .09 and that a greater percentage of
      patients with chronic pain are drug seekers (15% increasing to 24%, p = .004).
      The authors conclude that in the 3rd year of medical school students become less
      idealistic toward elderly patients, those with chronic pain, and the profession.

PMID- 11233587
TI  - Supporting children with serious health care needs. Analyzing the costs and
      benefits.
AB  - Effective and efficient service delivery to children who rely on medical
      technology or ongoing medical care will become increasingly critical as
      technology and medical know-how grow more sophisticated. Presently, technology's
      development and application threaten to outpace systems of service delivery. This
      article explores the present state of affairs by considering the challenges
      involved in planning and evaluating programs for children with special health
      care needs and their families. A cost-benefit model is suggested as a meaningful
      framework for considering challenges related to providing service in this arena
      and evaluating its effectiveness.

PMID- 11233588
TI  - Evaluation of patients' satisfaction with hospital-at-home care.
AB  - On July 1, 1997, in the Canton of Vaud, Switzerland, a pilot experiment of
      Hospital-at-Home Care (H-Hcare) was set up for a 2-year period at four sites to
      measure patients' satisfaction with this type of health care. Out of 174 patients
      referred to the H-Hcare program for a wide range of treatments, 107 were medical
      patients admitted for heart failure, community acquired pneumonia, or for an
      infectious disease requiring i.v.-antibiotherapy; 95 of these agreed to express H
      Hcare satisfaction and dissatisfactions during a semistructured interview
      conducted 6 weeks after admission. H-Hcare was considered a viable alternative to
      hospitalization when the illness is not too serious, and for patients who are
      still independent and need little care. When patients are more severely ill, they
      prefer to go to hospital to avoid overburdening their caregivers and to feel more
      secure.

PMID- 11233589
TI  - Chromosome walking by cloning of distinct PCR fragments.

PMID- 11233590
TI  - Scaling up the ligase chain reaction-based approach to gene synthesis.

PMID- 11233591
TI  - Improvement of the pBRINT-Ts plasmid family to obtain marker-free chromosomal
      insertion of cloned DNA in E. coli.

PMID- 11233592
TI  - Polyacrylamide gel as a matrix for the delivery of a layer or coat of other
      molecules.

PMID- 11233593
TI  - Running gels backwards to select DNA molecules larger than a minimum size.

PMID- 11233594
TI  - Method for the immunological detection of silver-stained proteins on
      nitrocellulose membranes.

PMID- 11233595
TI  - DNA isolation from chloroform/methanol-treated mycobacterial cells without
      lysozyme and proteinase K.

PMID- 11233596
TI  - A brief history of time-lapse.

PMID- 11233597
TI  - Immunomagnetic DNA aptamer assay.
AB  - DNA aptamers, oligonucleotides with antibody-like binding properties, are easy to
      manufacture and modify. As a class of molecules, they represent the biggest
      revolution to immunodiagnostics since the discovery of monoclonal antibodies. To
      demonstrate that DNA aptamers are versatile reagents for use as in vitro
      diagnostic tools, we developed a hybrid immunobead assay based on a 5'
      biotinylated DNA thrombin aptamer (5'-GGTTGGTGTGGTTGG-3') and an anti-thrombin
      antibody (EST-7). Our results show that the thrombin DNA aptamer is capable of
      binding to its target molecule under stringent in vitro assay conditions and at
      physiological concentrations. These findings also support the view that DNA
      aptamers have potential value as complementary reagents in diagnostic assays.

PMID- 11233598
TI  - Two-hybrid selection assay to identify proteins interacting with polymerase II
      transcription factors and regulators.
AB  - The RNA polymerase III-based two-hybrid system has been developed to detect
      interactions between proteins such as RNA polymerase II transcription factors and
      regulators that cannot be studied by the original RNA polymerase II two-hybrid
      system. This novel method appears to be most useful for a refined analysis of
      already known protein-protein interactions. However, the application of this
      system in library screenings has been impaired by the lack of a suitable assay
      for the selection of the activated pol III reporter gene in yeast. Here, we
      describe a novel selection assay for the pol III-based two-hybrid system that
      makes it readily usable for screening expression libraries to search for
      interacting partners. Our system utilizes a temperature-sensitive (ts) U6 snRNA,
      which is synthesized by RNA polymerase III from a mutated SNR6 gene in yeast. In
      this ts strain, interactions between hybrid proteins activate an artificial pol
      III reporter construct (UASG-SNR6), which controls expression of wild-type U6
      snRNA. This wild-type U6 snRNA can suppress the ts phenotype and allow growth at
      the nonpermissive temperature of 37 degrees C, thus providing a positive
      selection system for interacting proteins.

PMID- 11233599
TI  - Inside or outside: detecting the cellular location of bacterial pathogens.
AB  - Salmonella are intracellular pathogens that infect and multiply inside
      macrophages. Although Salmonella are some of the best-studied pathogens, it is
      difficult to determine quickly and reliably whether the bacteria are
      intracellular or extracellular. We have developed a novel method using
      differential fluorescence of two fluorescent proteins to determine the cellular
      location of pathogenic bacteria in macrophage infection assays. Using the
      differential expression of two unique fluorescent proteins that are expressed
      under specific conditions, we have developed a real-time assay for macrophage
      infections. The critical advantages of this system are that it does not alter the
      bacterial surface, it is not toxic to either the bacteria or the host cell, and
      it may be used in real-time quantitative assays. This assay can be readily
      applied to any other model pathogenic systems such as Listeria, Mycobacteria, and
      Legionella in which intracellular gene expression has been characterized.

PMID- 11233600
TI  - Protein aggregation mediated by cysteine oxidation during the stacking phase of
      discontinuous buffer SDS-PAGE.
AB  - The resolution of complex protein mixtures by discontinuous buffer SDS-PAGE is
      accomplished by their concentration into thin bands in the stacking gel, followed
      by their separation during migration through the resolving gel. Recombinant human
      interferon-inducible protein-10 (IP-10), a 10-kDa C-X-C chemokine with four
      cysteines, aggregated during the stacking phase of SDS-PAGE and generated a band
      with an apparent molecular mass of 18 kDa. This aggregation depended on the
      presence of reduced sulfhydryl residues on IP-10, on the amount of loaded
      protein, and on the concentration of the ammonium persulfate used to polymerize
      the stacking gel. The aggregation of IP-10 could be prevented by reduction of its
      sulfhydryls with dithiothreitol followed by irreversible blockade with
      iodoacetamide. These methods may be useful in the prevention of aggregation of
      sulfhydryl-containing proteins during SDS-PAGE, especially when large quantities
      are analyzed to assess their purity.

PMID- 11233601
TI  - High-throughput methods for detection of genetic variation.
AB  - Understanding human genetic variation is currently believed to reveal the cause
      of individual susceptibility to disease and the large variation observed in
      response to treatment. In this review, we will focus on different approaches to
      identify and visualize genetic alterations. The various approaches for allele
      discrimination are formally systematically divided into (i) enzymatic approaches,
      in which the properties of different enzymes to discriminate between nucleotides
      are used (restriction enzymes type II, Cleavase and Resolvase, DNA polymerase,
      and ligase); (ii) electrophoretic methods, in which the allele discrimination is
      based on the difference in mobility in polymeric gels or capillaries (single- and
      double-stranded conformation assays, heteroduplex analysis, and DNA sequencing);
      (iii) solid-phase determination of allelic variants, including high-density
      oligonucleotide arrays for hybridization analysis, minisequencing primer
      extension analysis, and fiberoptic DNA sensor array; (iv) chromatographic methods
      such as denaturing high-performance liquid chromatography (DHPLC); (v) other
      physical methods of discrimination of allelic variants such as mass spectrometry
      (mass and charge) or fluorescence exchange-based techniques; and (vi) in silico
      methods such as high-throughput analysis of expressed sequence tag data. The most
      frequently used techniques and instrumental settings applied in different
      combinations are described, and other methods that are less broadly used but have
      interesting potentials are discussed.

PMID- 11233602
TI  - High-throughput conformation-sensitive gel electrophoresis for discovery of SNPs.
AB  - High-throughput screening for single nucleotide polymorphisms (SNPs) or mutations
      can be achieved by inexpensive technologies. We modified the original protocols
      of conformation-sensitive gel electrophoresis (CSGE) to increase throughput
      several fold to 1.3 samples/min, which is about five times faster than denaturing
      high-performance liquid chromatography (DHPLC). The modifications include
      decreasing the gel thickness, increasing the number of lanes to 96, and
      increasing the number of samples per lane to seven. This high-throughput CSGE
      method is fast, robust, and as simple as the original protocols. Together with a
      two-stage strategy for screening homozygotes and the replacement of ethidium
      bromide with SYBR Gold DNA dye staining, this protocol is a reliable and cost
      effective alternative for laboratories that require high-throughput screening.

PMID- 11233603
TI  - High-resolution detection of loss of heterozygosity of dinucleotide
      microsatellite markers.
AB  - Dinucleotide microsatellite markers are frequently investigated to study
      inheritance, genetic stability, and allele frequency distribution in a wide
      variety of genetic disorders. Previous studies have encountered significant
      problems regarding resolution and detection of dinucleotide, microsatellites. In
      this study, a useful method to investigate loss of heterozygosity (LOH) of
      dinucleotide microsatellite markers is described that involves the use of
      nondenaturing (Spreadex) submerged gel electrophoresis and SYBR Green I nucleic
      acid staining. This method omits the gel casting step and the use of hazardous
      radioactive materials frequently used in many microsatellite studies that employ
      polyacrylamide gel nucleic acid denaturation analysis. Using this method, 62
      patients' paired tumor and normal samples were investigated to detect allele
      deletions in a region of chromosome 7q31.1, which is believed to harbor a tumor
      suppressor gene. Interpretable results were obtained in all cases. These results
      were compared to those attained using ABI Prism Genetic Analyzer 310 and Gene
      Scan. There were no discrepancies in results obtained between the two assays. The
      Spreadex system is cheap, does not require larger equipment costs, and may prove
      to be a useful system for high-throughput investigation of microsatellites. It
      may have diagnostic significance and also prove useful if applied to population
      based genomic screening and linkage analysis.

PMID- 11233604
TI  - High-throughput AFLP analysis using infrared dye-labeled primers and an automated
      DNA sequencer.
AB  - Amplified fragment length polymorphism (AFLP) analysis is currently the most
      powerful and efficient technique for the generation of large numbers of anonymous
      DNA markers in plant and animal genomes. We have developed a protocol for high
      throughput AFLP analysis that allows up to 70,000 polymorphic marker genotype
      determinations per week on a single automated DNA sequencer. This throughput is
      based on multiplexed PCR amplification of AFLP fragments using two different
      infrared dyelabeled primer combinations. The multiplexed AFLPs are resolved on a
      two-dye, model 4200 LI-COR automated DNA sequencer, and the digital images are
      scored using semi-automated scoring software specifically designed for complex
      AFLP banding patterns (AFLP-Quantar). Throughput is enhanced by using high
      quality genomic DNA templates obtained by a 96-well DNA isolation procedure.

PMID- 11233605
TI  - Melting curve analysis of SNPs (McSNP): a gel-free and inexpensive approach for
      SNP genotyping.
AB  - High-throughput methods for assaying DNA variation require two important steps:
      (i) discriminating the variation and (ii) detecting the signal. In this report,
      we describe a novel SNP genotyping method that we refer to as melting curve
      analysis of SNPs (McSNP). McSNP combines a classic approach for discriminating
      alleles, restriction enzyme digestion, with a more recent method for detecting
      DNA fragments, melting curve analysis. Melting curve analysis is performed by
      slowly heating DNA fragments in the presence of the dsDNA-specific fluorescent
      dye SYBR Green I. As the sample is heated, fluorescence rapidly decreases when
      the melting temperature of a particular fragment is reached. We show that it is
      possible to determine the composition of simple mixtures of DNA fragments, such
      as those that result from restriction enzyme digestions of short PCR products.
      McSNP is well suited for high-throughput genotyping because 96 samples can be
      analyzed and automatically scored in 20 min. Our results clearly demonstrate that
      McSNP is a simple, inexpensive, and accurate means of genotyping SNP variation.

PMID- 11233606
TI  - Fabrication of DNA microarrays using unmodified oligonucleotide probes.
AB  - Microarrays printed on glass slides are often constructed by covalently linking
      oligonucleotide probes to a derivatized surface. These procedures typically
      require relatively expensive amine- or thiol-modified oligonucleotide probes that
      add considerable expense to larger arrays. We describe a system by which
      unmodified oligonucleotide probes are bound to either nonderivatized or epoxy
      silane-derivatized glass slides. Biotinylated PCR products are heat denatured,
      hybridized to the arrays, and detected using an enzymatic amplification system.
      Unmodified probes appear to detach from the slide surface at high pH (> 10.0),
      suggesting that hydrogen bonding plays a significant role in probe attachment.
      Regardless of surface preparation, high temperature (up to 65 degrees C) and low
      ionic strength (deionized water) do not disturb probe attachment; hence, the
      fabrication method described here is suitable for a wide range of hybridization
      stringencies and conditions. We illustrate kinetics of room temperature
      hybridizations for probes attached to nonderivatized slides, and we demonstrate
      that unmodified probes produce hybridization signals equal to amine-modified,
      covalently bound probes. Our method provides a cost-effective alternative to
      conventional attachment strategies that is particularly suitable for genotyping
      PCR products with nucleic acid microarrays.

PMID- 11233607
TI  - The RITE assay: identifying effectors that target the transcription machinery
      using phage display technology.
AB  - We describe an approach using phage display to identify effectors (activators and
      repressors) of transcription based on the particular component of the general
      transcription machinery that they target. We refer to this approach as the
      reverse identification of transcriptional effectors (RITE) assay. A library of
      phages containing cDNA-encoded peptides displayed on their surfaces is screened
      using as the target a specific region of one of the general transcription factors
      (e.g., the C terminus of hTAFII135). The amino acid sequence encoded by the cDNA
      of an interacting phage is determined and analyzed in a database homology search
      to identify known or novel factors that may interact with the target protein.
      Candidate effectors from the homology search are synthesized from recombinant
      clones and tested for their abilities to bind to the target protein and to
      functionally modulate transcription in vivo when co-expressed with the
      transcriptional target protein. Because the RITE assay is a direct measure of the
      interactions between general transcription proteins and their effectors, it has
      an advantage over the well-known yeast two-hybrid system, which is not amenable
      to identifying transcription factor interactions.

PMID- 11233608
TI  - Lateral view flow system for studies of cell adhesion and deformation under flow
      conditions.
AB  - Physical interactions between circulating cells and the vascular wall play a
      central role in inflammation, metastasis, atherosclerosis, and therapeutic cell
      delivery. Unfortunately, traditional in vitro flow assays cannot be used to
      visualize the details of cell-surface interactions in blood flow because of
      inappropriate geometry and the poor penetration of light in erythrocyte
      solutions. To overcome these obstacles, we have developed an agarose-cast
      cylindrical vessel system to examine the profiles of cells interacting with
      surfaces under flow conditions. This design allows observation and quantification
      of cell deformation as cells adhere to surfaces under dynamic flow conditions
      without modifying the microscope or optical path. Furthermore, our flow system is
      uniquely suited for monitoring the profiles of adherent leukocytes deforming in
      response to erythrocyte suspension flow. We have used this flow system to study
      the role of erythrocytes in leukocyte-substrate interactions. Our results show
      that the cell deformation index (the ratio of the cell length to cell height) is
      higher in erythrocyte solutions compared to erythrocyte-free saline. This novel
      lateral view flow system provides a powerful technique for visualizing and
      quantifying the morphological changes of cells in contact with substrates exposed
      to shear stress.

PMID- 11233609
TI  - Sensitive measurement of polyethylene glycol-modified proteins.
AB  - An IgM monoclonal antibody (AGP3) against polyethylene glycol (PEG) was used to
      assay PEG-modified proteins by ELISA. PEG-modified beta-glucuronidase could be
      measured at concentrations as low as 15 ng/mL, corresponding to 750 pg (1.8 fmol)
      of conjugate. This ELISA should be generally applicable to all PEG-modified
      proteins because AGP3 binds the backbone of the PEG chain independent of the
      linker used for PEG attachment.

PMID- 11233610
TI  - Selection of scFv phages on intact cells under low pH conditions leads to a
      significant loss of insert-free phages.
AB  - Display of functional antibody fragments on the surface of filamentous
      bacteriophages allows fast selection of specific phage antibodies against a
      variety of target antigens. However, enrichment of single chain variable fragment
      (scFv)-displaying phages is often hampered by the abundance of bacteriophages
      lacking antibody fragments. Moderate adhesive binding activities and production
      advantages of these "empty" phages results in their subsequent enrichment during
      selection on target cells. To date, very limited effort has been made to develop
      strategies removing nonspecific binding phages during the selection processes. To
      efficiently reduce insert-free phages when panning on intact cells, we increased
      the washing stringency by lowering the pH of the buffer with citric acid. Under
      standard washing procedures (pH 7.4), only approximately 73% of recovered phages
      were insert-free after three rounds of selection. Using stringent washing
      procedures (pH 5.0), approximately 12% of recovered phages contained no scFv.
      Using this protocol, we have cloned an antibody fragment from a mouse/human
      hybridoma cell line directed against the disialoganglioside GD2. This study
      confirms that selection of phage antibodies on cells is efficiently enhanced by
      assays augmenting the stringency to remove nonspecific binding phages.

PMID- 11233611
TI  - Amplification and direct sequence analysis of the 23S rRNA gene from thermophilic
      bacteria.
AB  - We present a simplified and fast method to obtain high-quality sequences directly
      from PCRs without the traditional gel purification. We also report on an improved
      method to obtain sequence-quality PCR products from microorganisms that are
      difficult to lyse with no need for DNA extraction. The technique uses exonuclease
      1 and shrimp alkaline phosphatase to degrade residual dNTPs and primers. Our
      technique is shown to work on both Gram-positive and Gram-negative bacteria.

PMID- 11233612
TI  - Serum-free recombinant production of adenovirus using a hollow fiber capillary
      system.
AB  - A novel method for the production of adenoviral vectors on a scale sufficient to
      support most research applications and early phase clinical trials is presented.
      This method utilizes serum-free cell culture medium and a hollow fiber cell
      culture apparatus. Significantly less time and space are required than in
      conventional methods, and the resulting adenovirus is collected in a much smaller
      volume, simplifying the purification steps. The protocol described is a
      reproducible, convenient, biologically safe, and environmentally sound method for
      the production of adenoviral vectors for laboratory use and has the potential to
      scale-up the adenovirus production for clinical use.

PMID- 11233613
TI  - Detection and identification of virulence factors in Yersinia pestis using SELDI
      ProteinChip system.
AB  - A rapid method for the detection, purification, and identification of proteins in
      bacterial extracts was developed using surface enhanced laser
      desorption/ionization (SELDI) ProteinChip technology. The effectiveness of this
      technique for monitoring the expression and identification of temperature- and
      calcium-regulated virulence factors of Yersinia pestis, the bacterium that causes
      human plague, is demonstrated. Y. pestis infection of its mammalian host is
      thought to be accompanied by rapid up-regulation of a number of genes following a
      shift from 26 degrees C (the temperature of the flea vector) to 37 degrees C (the
      temperature of the mammalian host). To model this process, Y. pestis cells were
      grown at 26 degrees C and 37 degrees C in a Ca(2+)-deficient medium. Through an
      initial protein profiling of the crude bacterial extract on strong anion exchange
      and copper affinity, ProteinChip arrays detected five proteins that were up
      regulated and three proteins that were down-regulated at 37 degrees C. Two of the
      proteins predominately expressed at 37 degrees C were semi-purified in less than
      two days. The two proteins were identified as catalase-peroxidase and Antigen 4.
      Aside from its speed, a salient feature of the SELDI technique is the microgram
      amounts of crude sample required for analysis.

PMID- 11233614
TI  - Bulbar presentations of myasthenia gravis in the elderly patient.
AB  - We report on three cases of patients whose primary symptoms of myasthenia gravis
      were related to the upper aerodigestive tract. Symptoms had been present
      unrecognized in all patients for up to three years, and one patient subsequently
      developed a myasthenic crisis. We highlight the clinical features of myasthenia
      gravis to allow its prompt recognition in patients presenting to the ENT surgeon
      or physician.

PMID- 11233615
TI  - Magnetic resonance imaging in the investigation of sensorineural hearing loss: is
      contrast enhancement still necessary?
AB  - High resolution T2-weighted magnetic resonance (MR) imaging has been proposed as
      a rapid, inexpensive means of investigating patients with sensorineural deafness,
      particularly to exclude vestibular schwannomas. Whether the accepted 'gold
      standard' of contrast-enhanced T1-weighted images can be omitted, however,
      remains controversial. Over a 22-month period the use of axial turbo-spin echo T2
      weighted images (T2W) were prospectively compared with contrast-enhanced T1
      weighted spin echo scans in the evaluation of 513 patients presenting with
      audiovestibular symptoms. A 2-D T2W turbo spin echo (TSE) sequence with 3 mm
      slices was used in 340 patients while a 3-D sequence with overlapping 1 mm slices
      was used in 173 patients. The T2-weighted image findings were documented and
      subsequently compared with contrast-enhanced images. With the 2-D sequence 24
      patients (25 lesions) had internal auditory meatus (IAM)/cerebello-pontine angle
      (CPA) masses identified by contrast-enhanced T1-weighted images, all of which
      were seen on the T2-weighted TSE sequence; there was one false positive 'mass' on
      the T2-weighted scans and one false negative case of IAM dural enhancement on T1
      weighted imaging; six were considered normal initially on the T2-weighted images
      although three were subtly abnormal in retrospect. With the 3-D sequence three
      acoustic neuromas were all identified correctly with no false positive and only
      one false negative result (labyrinthitis). The 2-D and 3-D images were judged
      technically inadequate for clinical assessment in 15 and nine per cent
      respectively. We conclude that mass lesions of the IAM/CPA can be reliably
      identified on T2W TSE imaging but labyrinthine lesions may be missed without
      contrast enhancement. This is of particular importance in planning the management
      of neurofibromatosis type 2. Non-neoplastic disorders of the inner ear are also
      likely to be missed.

PMID- 11233616
TI  - Repair of nasal septal perforations using local mucosal flaps and a composite
      cartilage graft.
AB  - The surgical closure of a nasal septal perforation is recognized as being
      particularly challenging. A series of 11 consecutive patients who underwent
      closure of a septal perforation using a mucosal flap/composite conchal cartilage
      graft technique are reviewed, and the surgical technique described. The size of
      the perforation repaired varied, with eight cases being 2 cm or more in diameter.
      There was no significant graft donor site morbidity and complete perforation
      closure was achieved in eight cases after a mean observation time of 19.8 months.
      These results suggest that this is a suitable technique for closing nasal septal
      perforation.

PMID- 11233617
TI  - Survey of computed tomography scanning and endoscopic sinus surgery in a group of
      district general hospitals in south Essex.
AB  - The management of chronic sino-nasal disease has changed significantly in the
      last 15 years with the advent of topical nasal steroids and minimally invasive
      endoscopic surgery, but survey data from district hospitals in the UK have not
      been published to date. We examined the current management of 383 consecutively
      scanned patients with sino-nasal symptoms in three district hospitals. Survey
      standards were set, and were attained in 56 per cent for symptom recording, 60
      per cent for pre-scan diagnosis, 62 per cent for endoscopic examination in out
      patients, and 73 per cent for topical steroid use before scanning. The
      variability of sinus disease makes it difficult to be dogmatic about proper
      indications for surgery, but subsequent surgical management, as ascertained from
      the notes, showed large differences between consultants in the three hospitals.
      The rate of minor complications was 2.2 per cent, there were no major
      complications, and the vast majority of patients stated that their nasal symptoms
      were improved by surgery. The survey showed that endoscopic sinus surgery is safe
      and effective when practised in a district hospital setting.

PMID- 11233618
TI  - Acute epiglottitis: a review of 80 patients.
AB  - We reviewed 80 patients admitted to our hospital who were diagnosed with acute
      epiglottitis between January 1995 and March 1999, and their clinical features,
      evolution and treatments were analysed. No sexual predominance was found, and
      there was no patient younger than 16 years of age. The patient fatality rate was
      1.3 per cent, and the hospitalization period was markedly longer than those of
      other reports.

PMID- 11233619
TI  - Aryepiglottoplasty for laryngomalacia: 100 consecutive cases.
AB  - A retrospective review of the notes of 100 consecutive patients who had undergone
      aryepiglottoplasty for laryngomalacia, at Great Ormond Street Hospital for
      Children, was undertaken. Fifty-six were male, 44 female and 47 were under three
      months of age. Indications for surgery were oxygen desaturation below 92 per cent
      and feeding difficulties causing failure to thrive. Forty-seven patients had
      other pathology contributing to their airway compromise or feeding problems.
      Improvement in stridor after one month was achieved in 86/91 (94.5 per cent)
      being abolished completely in 50/91 (55 per cent). Of the 25 per cent of patients
      whose symptoms took more than one week to resolve, 16/22 (63.6 per cent) were
      later found to have a serious neurological condition. Feeding was improved in 42
      of 58 patients (72.4 per cent) who had a pre-operative feeding difficulty. The
      complication rate was low, with only five out of 86 (10 per cent) experiencing
      initial worsening of the airway and six per cent having aspiration of early feeds
      before improvement occurred. Endoscopic aryepiglottoplasty remains the operation
      of choice for patients with severe laryngomalacia, however, in the presence of
      neurological disease surgery is less likely to be successful.

PMID- 11233620
TI  - Role of a home care team in paediatric day-case tonsillectomy.
AB  - The feasibility of paediatric day-case tonsillectomy (PDCT) depends on its safety
      and acceptance by parents and patients. The purpose of our retrospective study of
      paediatric day-case tonsillectomy was to review the role of the home care team
      (HCT) in improving the safety and acceptance of the procedure. Between January
      1997 and June 1999, 352 consecutive children underwent day-case tonsillectomy.
      The notes and HCT assessment sheets were reviewed for telephone calls made by HCT
      or by parents, home visit by HCT, types of complication and their outcome. The
      primary haemorrhage rate was 0.6 per cent. The effective day-case rate was 97 per
      cent. The unplanned admission rate was three per cent. The HCT visited about 25
      per cent of patients at home. We conclude that paediatric day-case tonsillectomy
      is associated with high morbidity and considerable parental anxiety that can be
      dealt with by timely reassurance, support and advice by a dedicated HCT.

PMID- 11233621
TI  - Ear injuries caused by lightning: report of 18 cases.
AB  - The clinical management and long-term outcome in lightning survivors with
      substantial ear damage treated at the Department of Otorhinolaryngology,
      University Hospital Split during the 1984-1999 period are reviewed. Results of
      clinical management and outcomes of lightning ear damage in 18 patients (mean age
      35.3 +/- 5 years) were retrospectively analyzed. On admission, all patients
      complained of severe pain, tinnitus and hearing impairment. Otomicroscopy
      revealed tympanic membrane rupture in 12 patients. The active therapeutic
      approach included immediate otomicroscopy, aseptic aspiration toilet, and
      eversion of perforation edges. In all patients, the ruptures healed well, and
      restitution of the hearing function was achieved. Follow-up examination performed
      in 1999 (13.2 +/- 2.9 years later) in 11 patients (mean age 52.3 +/- 6.1 years)
      revealed an almost identical audiogram as on discharge from the hospital,
      however, neuropsychological testing revealed numerous sequelae. Tympanic injury
      caused by lightning should be actively treated. Lightning survivors require
      additional psychotherapeutic treatment.

PMID- 11233622
TI  - Self-retaining aural speculum: a valuable aid to middle-ear surgery.
AB  - We report the use of a self-retaining aural speculum that provides an excellent
      view of the middle ear through a small endural incision. We have found this
      instrument of value in tympanoplasty and stapes surgery in particular.

PMID- 11233623
TI  - Wegener's granulomatosis: diagnostic dilemma.
AB  - Wegener's granulomatosis is a systemic disease characterized by a granulomatous
      lesion that can affect any organ throughout the body. This case-report
      illustrates the problem posed by a patient presenting with bilateral serous
      otitis media with marked sensorineural hearing loss, facial nerve paralysis and
      an atypical serological picture. The importance of early diagnosis and the
      protocol for the management of a patient with an uncertain diagnosis is
      discussed. Due to atypical presentations, only a high index of suspicion will
      ensure an early diagnosis.

PMID- 11233624
TI  - Meningioma in the internal auditory canal.
AB  - A case is presented of an entirely intracanalicular meningioma in a 48-year-old
      woman that was excised via a conventional translabyrinthine approach to the
      internal auditory canal (IAC). Pre-operative magnetic resonance imaging (MRI)
      suggested that the tumour was a vestibular schwannoma (VS). Histological
      examination confirmed the intra-operative impression that the tumour was a
      meningioma. Although VS is by far the commonest intracanalicular tumour, the
      differential diagnosis includes meningioma. MRI is unable to distinguish between
      these two entities when the tumour is located entirely in the internal auditory
      canal.

PMID- 11233625
TI  - Schwannoma of the chorda tympani.
AB  - The authors present a rare clinical entity in a schwannoma of the chorda tympani.
      The case is discussed including the difficulty in making the diagnosis and
      management.

PMID- 11233626
TI  - Congenital facial nerve agenesis.
AB  - We present a case of a seven-year-old child with a congenital facial palsy,
      diagnosed at birth, who subsequently developed a non-tuberculous mycobacterial
      (NTM) infection of the ipsilateral parotid gland. This required parotid
      exploration to treat the NTM disease with the intention of identifying and
      protecting the facial nerve to preserve any residual facial nerve function. At
      operation, thorough exploration revealed the complete absence of the nerve both
      at the stylomastoid foramen and more peripherally within the substance of the
      parotid gland. Exploration of the facial nerve for congenital facial paralysis is
      not normally indicated. Surgical treatment, if required, tends to involve the use
      of techniques such as cross facial nerve and free vascularized muscle grafting.
      To our knowledge this is the first reported case of complete congenital facial
      nerve agenesis, diagnosed incidentally during a surgical procedure for an
      unrelated condition.

PMID- 11233627
TI  - Primary sinonasal amyloidosis.
AB  - Primary amyloidosis localized to the sinonasal tract is extremely rare with only
      20 reported cases in the English literature. We describe a further case and
      review the literature.

PMID- 11233628
TI  - Post-nasal space oncocytoma: a different approach to a rare tumour.
AB  - Oncocytomas are rare tumours that occur predominantly in the major salivary
      glands, particularly the parotid of older individuals. We present the
      exceptionally rare occurrence of an oncocytoma in the post-nasal space and its
      treatment for the first time via a Le Fort I osteotomy. The potential for local
      spread to the surrounding skull base makes it vital to achieve good oncological
      clearance. We found that this was possible using the Le Fort I technique and
      would recommend that this approach should be considered in future, when
      approaching such lesions.

PMID- 11233629
TI  - First case of surgically corrected puberphonia.
AB  - Puberphonia is predominantly a male condition which, normally affecting
      teenagers, may present in later life. It is defined as the failure to change from
      the high-pitched voice of the pre-adolescence to the lower pitched voice of
      adulthood. Patient previously reported have responded to voice therapy alone. We
      report the first surgically corrected case.

PMID- 11233630
TI  - Sensory deprivation as a consequence of severe head and neck lymphoedema.
AB  - We report a case of sensory deprivation that occurred as a consequence of
      progressive head and neck lymphoedema, following combined surgery and
      radiotherapy for squamous cell carcinoma. The management of head and neck
      lymphoedema is discussed and measures are suggested for improving the sensory
      deprivation experienced by the worst affected patients.

PMID- 11233631
TI  - Intramasseteric metastasis of renal cell carcinoma.
AB  - In this case report, we present a solitary metastasis of renal cell carcinoma
      inside the masseter muscle. To our knowledge, it is the very first case ever
      encountered.

PMID- 11233632
TI  - Submasseteric abscess.
AB  - The masseteric space is an important tissue compartment of the neck, but disease
      in it is difficult to diagnose and treat. In this paper a case of a young adult
      male with an abscess of the submasseteric space is presented. Diagnosis was
      established by computed tomography (CT) of the neck, but the severity of the
      lesion was not accurately estimated. Surgical intervention was performed and a
      large quantity of pus was drained. A detailed medical history and clinical
      examination of the patient as well as CT are important tools in the accurate
      diagnosis and efficient treatment of the disease.

PMID- 11233633
TI  - Occipital meningocele and Mondini deformity of the cochlea.
AB  - We present two cases of a previously unreported association between occipital
      meningocele and Mondini deformity of the cochlea. The probability of the
      association is supported by the intimate relationship between the development of
      these structures; the existence of dysembryoplastic factors that can cause both
      abnormalities; and the universal existence of cochlear abnormalities in
      anencephalic foetuses. The importance of considering the association is
      emphasized, in terms of early identification and referral of children with
      hearing loss, and avoidance of duplication of investigations.

PMID- 11233634
TI  - Extraskeletal Ewing's sarcoma of the nose.
AB  - A 20-year-old woman presented with nasal obstruction and slight epistaxis. The
      obstructing lesion was excised and microscopy showed a neoplasm composed of
      comparatively uniform undifferentiated cells forming solid nests. The cytoplasm
      of the cells was clear but poorly demarcated, partly vacuolated and contained
      much glycogen. Although widespread in the nasal mucosa, the cells did not
      penetrate into the underlying bone. The cells expressed the MIC2 gene (using the
      CD99 marker). Electron microscopy showed simple cells with a small number of
      mitochondria, many glycogen particles; there were no neurosecretory granules
      present. Early surgical treatment followed by chemo- and radiotherapy have
      greatly improved the prognosis of EWS: extraskeletal Ewing's sarcoma (EWS/PNET).

PMID- 11233636
TI  - Arcuate eminence in Caucasian populations.
AB  - The arcuate eminence (AE) was studied in 21 Caucasian cadavers (42 temporal
      bones), with particular reference to its relationship to the superior
      semicircular canal (SSC) and the temporal lobe. An arc-like eminence was observed
      in over 80 per cent of specimens, however, they did not exactly correspond to the
      SSC and such eminences corresponded to the sulci of the temporal lobe. The round
      and domed eminence corresponded to each SSC in seven temporal bones. The
      distances between the SSC and the middle cranial fossa were varied (0-2.5 mm,
      mean: 1.2 mm+ +/- 0.6 mm) whereas distances between the lateral semicircular
      canal and tympanic cavity were relatively consistent (0.6-1.4 mm, mean: 1.0 mm +/
      0.2 mm). These data indicate that the AE is trace of the temporal lobe and the
      SSC gave little effect to the surface of the middle cranial fossa. These findings
      could well be applicable to all humans.

PMID- 11233635
TI  - Haemangiopericytoma of infratemporal fossa.
AB  - Haemangiopericytomas (HPCs) are rare vascular tumours that commonly involve the
      soft tissues of the trunk and lower extremities. In the head and neck, the most
      common sites are the nasal cavity and the paranasal sinuses, and unusually, the
      orbital region, the parotid gland, and the neck. We report a patient with HPC
      that originated in the infratemporal fossa and involved the pterygopalatine and
      the middle cranial fossae, apparently the first such case to be reported.
      Although the patient has undergone resection on three separate occasions, the
      tumour recurred. We then performed an extended resection using the infratemporal
      fossa approach type D. The patient has shown no recurrence in the past five
      years. Although histopathologic confirmation of this malignancy may be difficult,
      extensive resection remains the most effective treatment in such cases.

PMID- 11233637
TI  - Photochemistry and phototoxicity studies of flutamide, a phototoxic anti-cancer
      drug.
AB  - The phototoxic anti-cancer drug flutamide is photolabile under UV-B light in
      either aerobic or anaerobic conditions. Irradiation of a methanol solution of
      this drug produces several photoproducts, one by photoreduction of the nitro
      group, one by rupture of the aromatic-NO2 bond of the parent compound, two as a
      result of the rupture of the CO-NH bond and one derived from the photoreduction
      product by scission of the aromatic-NH2 bond. Flutamide shows a photohemolytic
      effect on human erythrocytes and photoinduces lipid peroxidation. Studies on
      peripheral blood polymorphonuclear cells (neutrophils) demonstrated the
      phototoxicity of flutamide as well as inhibition of the cytotoxicity respiratory
      burst by the photoproduct derived from its photoreduction. The results suggest
      that the inhibition of the respiratory burst observed in phorbol myristate
      acetate (PMA)-activated cells is mediated by photosensitization and concomitant
      singlet oxygen production and/or formation of toxic photoproducts.

PMID- 11233639
TI  - On recording the true absorption spectrum and the scattering spectrum of a turbid
      sample: application to cell suspensions of the cyanobacterium Anabaena
      variabilis.
AB  - An integrating sphere is often used for recording the absorption spectrum of a
      turbid sample. If the sample is placed inside the sphere, scattering losses are
      eliminated, but the recorded spectrum suffers from other distortions. These
      distortions can be avoided by positioning the sample outside the sphere; but,
      since some of the scattered light escapes the detector, the recorded spectrum
      suffers from residual scattering losses. A method proposed by Latimer and Eubanks
      more than 30 years ago (Arch. Biochem. Biophys. 98 (1962) 274), is put to a
      quantitative examination, which has shown that one can obtain, by recording two
      spectra at different distances from the sphere, not only the true absorption
      spectrum but also the scattering spectra of the sample. Conditions for the
      validity of the basic assumption underlying the method are investigated by
      examining suspensions containing various concentrations of cells of the
      cyanobacterium Anabaena variabilis, and it is shown that the calculated
      absorbance is proportional to the number density of the cells. The application of
      the method for quantitative spectrophotometric analysis of pigments in cell
      suspensions is discussed.

PMID- 11233638
TI  - Photoprotective compounds in cyanobacteria, phytoplankton and macroalgae--a
      database.
AB  - A database on photoprotective compounds in cyanobacteria, phytoplankton and
      macroalgae has been developed. It contains information on photoprotective
      compounds such as mycosporine-like amino acids (MAAs), scytonemin and other not
      yet identified compounds reported in aquatic organisms, their habitat, the
      collection site and date and the reference. Further information on the absorption
      maxima and extinction coefficients of different photoprotective compounds as well
      as experimental procedures are provided (see http:/ /www.biologie.uni
      erlangen.de/botanik1/index.html). The database answers the urgent need for a
      library on these substances and provides scientists in the field with the
      necessary information to identify and quantify screening pigments in different
      aquatic organisms from various growing sites and different collection dates.

PMID- 11233640
TI  - Homodimeric monomethine cyanine dyes as fluorescent probes of biopolymers.
AB  - The fluorescence properties of newly synthesized homodimeric monomethine cyanine
      dyes in the presence of biopolymers are investigated. They do not fluoresce in TE
      buffer and bidistilled water but become strongly fluorescent (Q(F)=0.3-0.9) in
      the region 530-650 nm when bound to dsDNA and ssDNA. The detection limit of dsDNA
      is about 1.7 ng/ml. Some of dyes studied are able to distinguish between dsDNA
      and ssDNA, RNA, BSA in solution and gel electrophoresis. The influence of
      different factors (temperature, pH and viscosity of the medium, presence of
      histone) on the formation of the dye-biopolymer complexes is investigated. The
      results of steady-state and dynamic fluorescence measurements concerning the
      different types of binding between dyes and biopolymers show that the new dyes
      are applicable in molecular biology as highly sensitive fluorescence labels.

PMID- 11233641
TI  - Spectroscopic study of trypsin, heat and triton X-100-induced denaturation of the
      chlorophyll-binding protein CP43.
AB  - Trypsin-, heat- and Triton X-100-induced denaturation of CP43, the core antenna
      complex of photosystem II purified from spinach, has been investigated using
      absorption, fluorescence and circular dichroism spectroscopy. Triton X-100 was
      found to bring about considerable dissolution of pigments from the protein to the
      monomeric state in solution and destruction of the interactions among the
      chlorophyll, carotene and protein. Heat induced significant unfolding of the
      protein secondary structure and loss of excitonic interactions of the pigments,
      but no apparent dissolution of the pigments from CP43. Trypsin caused structural
      changes in the extrinsic part of the protein but no change of the native state of
      the pigments. Trypsin, heat and Triton X-100 treatments increased the light
      sensitivity of chlorophyll in CP43 to different extents. The results suggest that
      the protein and beta-carotene can protect the chlorophyll from light-induced
      destruction in CP43.

PMID- 11233642
TI  - Quenching of singlet oxygen (1deltag) by cobalt complexes with four nitrogen
      atoms in the equatorial plane.
AB  - The quenching of singlet oxygen (1deltag) by cobalt(III)-bis-1,2-benzosemiquinone
      diiminato complexes (general structure LCo(111)(BQDI)2ClO4) has been studied in
      different solvents by measuring the singlet oxygen phosphorescence decay in time
      resolved experiments. The axial ligand (Ph3As, Ph3Sb, N-methyl-imidazole,
      pyrrolidine) has practically no influence on the quenching; however, the
      chlorinated benzosemiquinone-diiminato complex has a markedly lower quenching
      rate constant. The solvent effects can be fully explained by the difference in
      viscosity, which supports the assumption that the quenching is diffusion
      controlled. The reactive radius of the encounter pair has been estimated to be
      0.3 nm, shorter than the radius of the complex itself, which points to the fact
      that singlet oxygen must approach the central cobalt atom at the (partially) open
      axial position. The significance of these results regarding the quenching of
      singlet oxygen by vitamin B12 derivatives is discussed.

PMID- 11233643
TI  - Oxygen monitoring during 5-aminolaevulinic acid induced photodynamic therapy in
      normal rat colon. Comparison of continuous and fractionated light regimes.
AB  - Currently, the clinical use of 5-aminolaevulinic acid (ALA) induced
      protoporphyrin IX (PPIX) for photodynamic therapy (PDT) is limited by the maximum
      tolerated oral ALA dose (60 mg/kg). Attempts have been made to enhance this
      treatment modality without increasing the administered dose of ALA. One way to do
      this is through light dose fractionation, where the irradiation is interrupted at
      a particular point for a short period of time. This can produce up to three times
      more necrosis than with the same light dose delivered without a break. An oxygen
      microelectrode was employed to study the effect of continuous and fractionated
      light regimes on the level of oxygen in the colon of normal Wistar rats during
      ALA PDT. A rapid decline in pO2 occurred close to the irradiation fibre as soon
      as the light dose commenced. With the fractionated regime, a partial recovery in
      pO2 was observed during the dark interval which was reversed soon after the
      second light fraction commenced. We have shown that the level of tissue oxygen at
      the treatment site is affected differently when the light dose is fractionated,
      than when continuous illumination is employed. This factor may at least partially
      explain the difference in outcome of these two treatment regimes. Further, oxygen
      measurements might prove to be a useful way of monitoring PDT treatments if they
      can predict whether tissue is likely to be viable following treatment.

PMID- 11233644
TI  - Time-resolved fluorescence reveals two binding sites of 1,8-ANS in intact human
      oxyhemoglobin.
AB  - Time-resolved fluorescence of 1,8-anilinonaphthalene sulfonate (1,8-ANS)
      fluorescent probe bound to intact human oxyhemoglobin (HbO2) is investigated.
      Fluorescence emission spectra of 1,8-ANS in a potassium buffer solution (pH 7.4)
      of HbO2 undergo a substantial blue shift during first 6 ns after pulsed optical
      excitation at 337.1 nm. Nonexponential fluorescence kinetics of 1,8-ANS in the
      HbO2 solution are studied by the decay time distribution and conventional
      multiexponential analyses for a set of emission wavelength range of lambdaem =
      455-600 nm. These fluorescence decays contain components with mean decay times of
      <0.5 ns, 3.1-5.5 ns, and 12.4-15.1 ns with spectrally-dependent relative
      contributions. The shortest decay component is assigned to free 1,8-ANS molecules
      in the bulk buffer environment, whereas the two longer decay components are
      assigned to two types of binding sites of 1,8-ANS in the HbO2 molecule presumably
      differing by polarity and accessibility to water molecules. The results represent
      the first experimental evidence of heterogeneous binding of 1,8-ANS to intact
      human oxyhemoglobin.

PMID- 11233645
TI  - The effect of lipid environment in purple membrane on bacteriorhodopsin.
AB  - The decay rate of the Bacteriorhodopsin (BR) photocycle intermediate M412 and
      proton, the proton pump efficiency (H+/M412), the ratios of M412 to other
      intermediates and the rotational correlation time (tauc) in purple membrane (PM)
      fragments treated by the zwitterionic detergent 3-[(3-cholamidopropyl)
      dimethylammonio]-1-propanesulfonate (CHAPS) with different concentrations were
      studied. The results show that: (1) The largest effect of CHAPS on M412 decay
      rate and proton decay rate of BR, tauc of PM and the ratios of M412 to other
      intermediates in BR photocycle is in the range of its critical micelle
      concentration (CMC). This indicates that changes of the ratios of M412 to other
      intermediates, tauc, M412 decay and proton decay occur and are due to the
      variation of the lipid environment. (2) The dependency of proton yield on CHAPS
      concentrations is basically consistent with that of M412s%. This indicates the
      relation between proton pumping function and M412. These studies show the
      importance of maintaining a native environment.

PMID- 11233646
TI  - Bilirubin- and light induced cell death in a murine lymphoma cell line.
AB  - Cells from the mouse lymphoma cell line L5178Y-R were exposed to blue light from
      phototherapy lamps in the presence of solutions of 160 microM bilirubin
      supplemented with serum albumin. HPLC analysis showed that the bilirubin solution
      was photooxidised as a function of increasing light dose. The cells were stained
      with trypan blue to score necrosis, and apoptosis was assayed by the terminal
      deoxynucleotide transferase assay (TdT) or by studying the nuclear structure in
      cells stained with propidium iodide. A rapidly developing apoptosis was observed
      after light doses killing 60-80% of the cells as judged from the trypan blue
      exclusion test. The fraction of apoptotic cells was smaller than the fraction of
      necrotic cells. Exposure of the cells to fractions of light at a high dose rate
      was compared to the effect of the same total dose at a lower dose rate given as a
      single fraction. No large differences were found, however, there was a tendency
      of a higher degree of necrosis as well as apoptosis in the cells receiving the
      light in fractions at a high dose rate.

PMID- 11233647
TI  - A note on the analysis of ligand binding by the 'double-logarithmic' plot.
AB  - The double-logarithmic plot has been employed for the fluorometric analysis of
      ligand binding. This analysis is valid only for 1:1 binding of a non-aggregating
      ligand and if the plot is based on the free, and not the total, ligand
      concentration.

PMID- 11233648
TI  - ELDONET--European Light Dosimeter Network. Structure and functions of the ELDONET
      server.
AB  - The European Light Dosimeter Network (ELDONET) project has been designed with the
      purpose of establishing an efficient system to monitor solar radiation in Europe,
      in as many as possible locations. This paper describes the structure of the
      server that collects and processes the data acquired by the different stations
      belonging to the network, and makes them freely available on the Internet to the
      scientific community. The server is able to receive data either via FTP from the
      Internet or via modem and to process them looking for errors or inconsistencies.
      Moreover, it automatically generates graphs, Web-pages and FTP archives. The
      server has been active for some years in testing mode and is now fully operative.

PMID- 11233649
TI  - The discovery of the damaging effect of sunlight on bacteria.

PMID- 11233650
TI  - Photochemistry of supramolecular systems containing C60.
AB  - Fullerenes have been used successfully in the covalent assembly of supramolecular
      systems that mimic some of the electron transfer steps of photosynthetic reaction
      centers. In these constructs C60 is most often used as the primary electron
      acceptor; it is linked to cyclic tetrapyrroles or other chromophores which act as
      primary electron donors in photoinduced electron transfer processes. In
      artificial photosynthetic systems, fullerenes exhibit several differences from
      the superficially more biomimetic quinone electron acceptors. The lifetime of the
      initial charge-separated state in fullerene-based molecules is, in general,
      considerably longer than in comparable systems containing quinones. Moreover,
      photoinduced electron transfer processes take place in non-polar solvents and at
      low temperature in frozen glasses in a number of fullerene-based dyads and
      triads. These features are unusual in photosynthetic model systems that employ
      electron acceptors such as quinones, and are more reminiscent of electron
      transfer in natural reaction centers. This behavior can be attributed to a
      reduced sensitivity of the fullerene radical anion to solvent charge
      stabilization effects and small internal and solvent reorganization energies for
      electron transfer in the fullerene systems, relative to quinone-based systems.

PMID- 11233651
TI  - Luminescence quenching by DNA-bound viologens: effect of reactant identity on
      efficiency and dynamics of electron transfer in DNA.
AB  - Photoinduced electron transfer from two intercalating photoactive donors,
      Ru(phen)2dppz2+ and ethidium, to intercalating viologen acceptors of the N,N'
      dialkyl-6-(2'-pyridiniumyl)phenanthridinium family has been investigated through
      steady-state and time-resolved luminescence quenching measurements. Efficient
      quenching of the emission from these donors bound to DNA is observed at low
      concentrations of acceptor (1-10 eq.), and in time-resolved emission experiments
      it is determined that electron transfer occurs on the nanosecond time scale.
      Furthermore, transient absorption measurements confirm that the quenching is the
      result of a charge-transfer process; upon photoreaction of intercalated
      Ru(phen)2dppz2+ with a viologen acceptor, an intermediate with spectral
      properties resembling the expected charge-separated pair is observed. The
      quenching yields and kinetics obtained with this quencher are in marked contrast
      to those observed with these same donors paired with Rh(phi)2bpy3+ as an
      acceptor. The differing efficiencies of electron transfer for these
      donor/acceptor pairs bound to DNA as compared to others previously described are
      discussed qualitatively in terms of the structural and electronic properties of
      the different reactants.

PMID- 11233652
TI  - Characterization of intracellular calcium oscillations induced by extracellular
      nucleotides in HEp-2 cells.
AB  - The effect of extracellular nucleotides on the cytosolic calcium concentration of
      fluo-3-loaded HEp-2 cells was examined using confocal microscopy. Extracellular
      ATP and UTP at micromolar concentration induced cytosolic calcium oscillations in
      42-66% of the cells. Oscillations were usually sinusoid and their frequency
      depended only slightly on agonist concentration. Oscillations developed in
      calcium-free medium but were diminished by depletion of intracellular calcium
      stores with thapsigargin, indicating periodic calcium release from internal
      stores. Inhibition of phospholipase C with U73122 prevented the development of
      oscillations, while ryanodine did not abolish the response to extracellular
      nucleotides. Activation of protein kinase C with 4beta-phorbol 12-myristate 13
      acetate also prevented the development of oscillations. These results indicate
      that extracellular nucleotides induce periodic calcium release from inositol
      1,4,5-trisphosphate-sensitive pools in HEp-2 cells and that the inhibitory effect
      of protein kinase C on the phosphatidylinositol signaling pathway can contribute
      to the development of intracellular calcium oscillations.

PMID- 11233653
TI  - Quantification of the selective retention of palladium
      octabutoxynaphthalocyanine, a potential photothermal drug, in mouse tissues.
AB  - Palladium octabutoxynaphthalocyanine (PdNc(OBu)8) is a potential photothermal
      therapy (PTT) agent, absorbing strongly in the near-infrared region with no
      ability to induce photodynamic-type sensitisation (unlike many related
      napthalocyanines). We report here on the application of high pressure liquid
      chromatography (HPLC) with near-infrared absorption detection for the
      determination of the tissue accumulation and clearance of PdNc(OBu)8 in a tumour
      bearing mouse model (Balb/c mice with EMT6 carcinoma tumour). Due to its
      insolubility in aqueous-based solvents, the drug was delivered intraperitoneally
      in a Cremophor-containing vehicle. Good selective accumulation of the drug into
      the tumour versus muscle or skin is observed, with the best combination of
      selectivity and tumour concentration occurring at 24-72 h after drug
      administration. Clearance times are quite long. Comparison with other similar
      drugs as reported in the literature indicates that the Cremophor-containing
      vehicle is likely in large part responsible for the observed pharmacokinetic
      behaviour. This drug shows potential for PTT and will be investigated further for
      therapy in this animal model.

PMID- 11233654
TI  - Nonradiative and radiative deactivation of singlet molecular oxygen
      (O2(a1deltag)) in micellar media and microemulsions.
AB  - The effects of microheterogeneous media (micelles and microemulsions) on the
      lifetime and, to our knowledge for the first time, on the emission of singlet
      molecular oxygen (O2 (a1Ag), denoted as 1O2) were investigated. Micellar media
      and various types of microemulsions based on anionic (sodiumdodecyl sulfate),
      cationic (cetyltrimethylammonium chloride) or nonionic (Triton X-100) surfactants
      were formulated for this purpose. The nonradiative and radiative deactivation
      rate constants (k(d) and k(e), respectively) were determined in selected
      microheterogeneous media and in the pure solvents used for their formulation, by
      combining steady-state and time-resolved 1O2, luminescence detection techniques.
      We have shown that a simple additive model, as used in homogeneous mixtures of
      solvents, was inadequate for predicting values of k(d) and k(e) in organized
      media. In contrast, both 1O2 lifetimes (taudelta = 1/k(d)) and k(e) in the
      microheterogeneous systems investigated could be predicted with good precision
      from the composition of the media and the taudelta and k(e) values in the pure
      solvents, using a two-pseudophase kinetic model for the 1O2 distribution. Such a
      model takes into account the average times spent by 1O2 in the aqueous and
      lipophilic pseudo-phases of the organized media, the corresponding equilibrium
      constant (Keq) depending on the nature of the system.

PMID- 11233655
TI  - Intravenous cyclosporine in refractory pyoderma gangrenosum complicating
      inflammatory bowel disease.
AB  - BACKGROUND: Pyoderma gangrenosum complicates inflammatory bowel disease in 2-3%
      of patients and often fails to respond to antibiotics, steroids, surgical
      debridement or even colectomy. METHODS: We performed a retrospective chart
      analysis of 11 consecutive steroid-refractory pyoderma patients (5 ulcerative
      colitis, 6 Crohn's disease) referred to our practice and then treated with
      intravenous cyclosporine. Pyoderma gangrenosum was present on the extremities in
      10 patients, the face in 2, and stomas in 21. At initiation of intravenous
      cyclosporine, bowel activity was moderate in 3 patients, mild in 4, and inactive
      in 4. All patients received intravenous cyclosporine at a dose of 4 mg/kg/d for 7
      22 days. They were discharged on oral cyclosporine at a dose of 4-7 mg/kg/d.
      RESULTS: All 11 patients had closure of their pyoderma with a mean time to
      response of 4.5 days and a mean time to closure of 1.4 months. All seven patients
      with bowel activity went into remission. Nine patients were able to discontinue
      steroids, and nine were maintained on 6-mercaptopurine or azathioprine. One
      patient who could not tolerate 6-mercaptopurine had a recurrence of pyoderma. No
      patient experienced significant toxicity. CONCLUSION: Intravenous cyclosporine is
      the treatment of choice for pyoderma gangrenosum refractory to steroids and 6
      mercaptopurine should be used as maintenance therapy.

PMID- 11233656
TI  - Inflammation location, but not type, determines the increase in TGF-beta1 and IGF
      1 expression and collagen deposition in IBD intestine.
AB  - BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is frequently complicated
      by extracellular matrix (ECM) changes that may result in fibrosis. Transforming
      growth factor (TGF)-beta1 and insulin-like growth factor (IGF)-1 mediate numerous
      ECM changes. Our aim was to determine whether TGF-beta1 and IGF-1 are involved in
      intestinal ECM collagen regulation and what impact the inflammatory infiltrate
      has on their expression. METHODS: TGF-beta1 and IGF-1 mRNA and protein were
      assessed in fibrosed Crohn's disease (CD), inflamed CD, inflamed ulcerative
      colitis (UC), and control intestine using in situ hybridization and
      immunohistochemistry. Collagen types I and III were quantified by electron
      immunohistochemistry. RESULTS: In CD, increased TGF-beta1 and IGF-1 mRNA
      expression was transmural. In UC, the increase was confined to the lamina propria
      and submucosa. In both, distribution of TGF-beta1 and IGF-1 protein matched mRNA
      expression and coincided with the distribution of the inflammatory infiltrate. An
      increase in the collagen type III:I ratio in both CD and UC also coincided with
      the inflammatory infiltrate. CONCLUSIONS: These findings suggest that TGF-beta1
      and IGF-1 are involved in intestinal ECM remodeling in IBD, and their enhanced
      expression depends on the presence and location of inflammatory infiltrates
      rather than the type of IBD.

PMID- 11233657
TI  - A clustering of Crohn's disease in Mankato, Minnesota.
AB  - Infrequently, clusterings of Crohn's disease (CD) occur that suggest it is
      transmissible. We studied such a clustering. Graduates of the Mankato West High
      School Class of 1980 were contacted by mail and asked to respond, by self
      addressed postcard, to a six-item questionnaire about inflammatory bowel disease
      and CD. Responses were followed-up by telephone contact and additional mailings.
      Two visits were made to Mankato, Minnesota, to interview individuals with CD, to
      obtain medical records, radiographs, and sera, and to study environmental risk
      factors. Of the 320 graduates of the class of 1980, 285 were contacted. Seven
      cases of CD were identified, the equivalent of a prevalence of 2,400/100,000.
      Concerns were discovered that CD may have emanated from recreational swimming.
      Fecal coliform counts in excess of 200/dL, the standard above which water is
      regarded as unsafe for recreational use, had been recorded year after year for
      the Blue Earth River at Mankato and for the Minnesota River. Recent fecal
      coliform counts (1993-1995) of Lake Washington, Lake German/Jefferson, and Lake
      Shetek were greater than 200/dL in 57%, 65%, and 62% of water samples. This
      clustering, in unrelated individuals, argues against a genetic cause for CD and
      suggests that environmental transmission occurred.

PMID- 11233658
TI  - Successful desensitization and therapeutic use of infliximab in adult and
      pediatric Crohn's disease patients with prior anaphylactic reaction.
AB  - Infusion of the antitumor necrosis factor-alpha chimeric monoclonal antibody
      infliximab is highly effective in the treatment of refractory and fistulizing
      Crohn's disease (CD), but can be associated with the development of severe
      allergic reactions during retreatment, precluding further use of the medication.
      We present two CD patients (one adult and one child) with a history of
      anaphylactic/anaphylactoid reactions to retreatment with infliximab who
      subsequently underwent successful desensitization and therapeutic infusion using
      parenteral dose escalation in an intensive care unit setting.

PMID- 11233659
TI  - Infliximab for the treatment of orofacial Crohn's disease.
AB  - Orofacial manifestations of Crohn's disease can be difficult to diagnose and
      treat. We report a case in which the orofacial lesions occurred 7 years prior to
      the diagnosis of underlying inflammatory bowel disease. The patient was
      refractory to mesalamine and systemic corticosteroids but responded to
      infliximab, the chimeric monoclonal antibody to tumor necrosis factor (TNF
      alpha). A review of the literature of the orofacial granulomatoses is presented
      as well.

PMID- 11233660
TI  - Paneth cell defensins and innate immunity of the small bowel.

PMID- 11233661
TI  - Measles virus and Crohn's disease: a critical appraisal of the current
      literature.
AB  - The etiology of inflammatory bowel disease (IBD) is unknown. Recent reports in
      the literature have suggested that measles virus, both wild-type and vaccine
      attenuated, might be a risk factor for Crohn's disease. We used the well-accepted
      Bradford-Hill criteria to evaluate the possible causal association between
      measles and IBD. Although the association may be biologically plausible, the
      literature lacks consistency, specificity, strength, and dose response. The
      current literature does not support an association between measles virus and IBD.

PMID- 11233662
TI  - Budesonide: is no evidence of a difference the same as evidence of no difference?

PMID- 11233663
TI  - The use of budesonide in the treatment of active Crohn's disease is good clinical
      practice.

PMID- 11233664
TI  - The placebo response and the "natural history" of inflammatory bowel disease.

PMID- 11233665
TI  - Mechanisms and modulation of intestinal epithelial repair.
AB  - The mucosal epithelium of the alimentary tract represents a crucial barrier to a
      broad spectrum of noxious and immunogenic substances within the intestinal lumen.
      An impairment of the integrity of the mucosal epithelial barrier is observed in
      the course of various intestinal disorders including inflammatory bowel diseases
      (IBD), celiac disease, intestinal infections, and various other diseases.
      Furthermore, even under physiologic conditions temporary damage of the epithelial
      surface mucosa may be caused by proteases, residential flora, dietary compounds,
      or other factors. Generally, the integrity of the intestinal mucosal surface
      barrier is rapidly reestablished even after extensive destruction because of an
      enormous regenerative capability of the mucosal surface epithelium. Rapid
      resealing of the surface epithelium is accomplished by epithelial cell migration,
      also termed epithelial restitution, epithelial cell proliferation, and
      differentiation. Healing of the intestinal surface epithelium is regulated by a
      complex network of highly divergent factors, among them a broad spectrum of
      structurally distinct regulatory peptides that have been identified within the
      mucosa of the intestinal tract. These regulatory peptides, conventionally
      designated as growth factors and cytokines, play an essential role in regulating
      differential epithelial cell functions to preserve normal homeostasis and
      integrity of the intestinal mucosa. In addition, a number of other peptide
      molecules such as extracellular matrix factors and blood clotting factors, and
      also nonpeptide molecules including phospholipids, shortchain fatty acids,
      adenine nucleotides, trace elements, and pharmacological agents, have been
      demonstrated to modulate intestinal epithelial repair mechanisms. Some of these
      molecules may be released by platelets, adjacent stromal cells, inflammatory
      cells, or injured epithelial and nonepithelial cells and may play an important
      role in the modulation of intestinal injury. Repeated damage and injury of the
      intestinal surface are key features of various intestinal disorders including IBD
      and require constant repair of the epithelium. Enhancement of intestinal repair
      mechanisms by regulatory peptides or other modulatory factors may provide future
      approaches for the treatment of diseases that are characterized by injuries of
      the epithelial surface.

PMID- 11233666
TI  - Anti-Saccharomyces cerevisiae antibodies (ASCA), phenotypes of IBD, and
      intestinal permeability: a study in IBD families.
AB  - BACKGROUND: Serologic markers anti-Saccharomyces cerevisiae antibodies (ASCA) and
      antineutrophil cytoplasmic antibodies with perinuclear staining (pANCA) have been
      proposed to study the immunopathogenesis of IBD. Their measurement may allow
      better phenotyping of the disease and the detection of subclinical disease. AIMS:
      To test the hypothesis that serological markers identify an immunologic trait
      related to disease susceptibility. We also wanted to test the hypothesis that
      ASCA is a marker related to abnormal tissue permeation by common antigens.
      METHODS: We studied the prevalence of pANCA and ASCA in a large cohort of
      sporadic and familial inflammatory bowel diseases and their unaffected relatives
      and spouses. Kinetics of ASCA was studied and the relationship between ASCA and
      51Cr-EDTA intestinal permeation was investigated. RESULTS: ASCA was associated
      with sporadic Crohn's disease (CD) (63%), with Crohn's patients belonging to pure
      CD families (62%) and also with their unaffected family members (21%). pANCA was
      associated with UC (58%). The prevalence of ASCA in CD patients belonging to
      mixed families was strikingly low (33%). ASCA was a stable marker throughout the
      disease and was not related to an increased small intestinal permeability.
      CONCLUSION: ASCA is strongly associated with familial CD in Belgium, and 21% of
      healthy family members also display the marker. The association is much weaker in
      patients belonging to mixed families. ASCA is a stable marker and is not a
      secondary phenomenon due to increased intestinal permeability.

PMID- 11233668
TI  - [Imported viral hepatitis A and B in the Czech Republic 1994-1999].
AB  - In 1994-1999 in the Czech Republic 8,036 cases of viral hepatitis A were
      notified, 205 (2.6%) being imported. During the same period 3,801 cases of viral
      hepatitis B were recorded incl. 44 (1.2%) imported ones. Transmission of viral
      hepatitis A was most frequent after tourist trips abroad, imported cases of viral
      hepatitis B were accounted for mostly by foreigners (40.9%) most frequently from
      the Ukraine. In both infections among patients males predominated--62.9% and
      63.6% resp. The highest risk for tourists is at present as trip to Asia. During
      the follow up period the attack rate was when calculated per 100,000 trips per
      year 4.2-5.1 and 0.5-0.6 resp. With regard to the so far limited interest in
      vaccination against the two infections before trips abroad it is desirable to
      promote the necessary knowledge not only among tourists but also among employees
      of travel agencies.

PMID- 11233667
TI  - [Persistence of Borrelia burgdorferi sensu lato in patients with Lyme
      borreliosis].
AB  - In 18 patients with Lyme borreliosis the authors proved the persistence of
      Borrelia burgdorferi sensu lato by detection of the causal agent by immune
      electron microscopy or of its DNA by PCR in plasma or cerebrospinal fluid after
      an interval of 4-68 months. Clinical manifestations common in Lyme borreliosis
      were present in only half the patients, in the remainder non-specific symptoms
      were found. In nine subjects with confirmed Borrelia burgdorferi sensu lato in
      the cerebrospinal fluid the cytological and biochemical finding was normal.
      Examination of antibodies by the ELISA method was negative in 7 of 18 patients
      during the first examination and in 12 of 18 during the second examination. In
      all negative examinations the specific antibodies were assessed by the Western
      blot or ELISA method after liberation from the immunocomplexes. In the authors'
      opinion it is advisable to examine repeatedly plasma and other biological
      material from potentially affected organs by PCR and subjects with persisting or
      relapsing complaints after the acute form of Lyme borreliosis as well as to
      examine cerebrospinal fluid in case on non-specific symptoms and concurrent
      pathic EEG or MR findings.

PMID- 11233669
TI  - [Intestinal parasites in children from the Turiec region in long-term monitoring.
      How should we proceed with further preventive parasitologic examinations?].
AB  - The results of preventive parasitological examinations for intestinal parasites
      in preschool and school children of the Turiec Region (Central Slovakia) in 1970
      1999 are submitted. The study is divided into three cross-sections in the
      following decades (1970-1979; 1980-1989; 1990-1999). An acute decrease in
      geohelminths virtually to zero values has been found, as well as a significant
      decrease in intestinal protozoans. The occurrence of Enterobius vermicularis,
      despite its significant decrease in the recent decade, remains on a relatively
      high level. In the conclusion the authors discuss continuation of parasitological
      field examinations, and, on the basis of their 30-year experience, they submit
      their recommendations for the simplest and most effective way of such
      examinations.

PMID- 11233670
TI  - [Effect of subinhibitory levels of aminoglycosides and fluoroquinolines on
      hydrophobicity and motility of Serratia marcescens].
AB  - The authors investigated the effect of subinhibitory quinolone concentrations
      (ciprofloxacin, enoxacin, norfloxacin, ofloxacin, pefloxacin) and aminoglycosides
      (amicacin, gentamicin, netilmicin, tobramycin) on the surface hydrophobicity and
      motility of the clinical isolate of Serratia marcescens. The hydrophobicity was
      evaluated by methods of adherence to the hydrocarbon xylene (BATH) in a salt
      aggregation ammonium sulphate (SAT) test. The tested quinolones in subinhibitory
      concentrations inhibited the adherence of S. marcescens to xylene with the
      exception of 1/16 MIC ofloxacin where slight stimulation took place. The most
      marked inhibition of adherence was observed after the action of 1/4 MIC
      ciprofloxacin (to 13.2%) and pefloxacin (to 31.0%) as compared with the control.
      Among aminoglycosides netilmicin markedly inhibited the adherence over the whole
      range of concentrations, whereby 1/8 MIC suppressed it to 0.7%. With these data
      correlated also the results of the salt-aggregation test. The investigated
      antibiotics did not have a major effect on the motility of S. marcescens.

PMID- 11233671
TI  - [Health and economic benefits of mandatory regular vaccination in Slovakia. IV.
      Measles, rubella and mumps].
AB  - The epidemiological situation as regards measles, rubella and mumps in Slovakia
      before vaccination and after its introduction in 1996, is analysed. On the basis
      of model costs of treatment of these diseases before vaccination and costs of
      treatment in 1996 including costs of vaccination, the authors calculated the
      total saved costs (549.7 mil. Sk), cost-effectiveness (10,680 Sk), as well as the
      cost-benefit.

PMID- 11233672
TI  - [Is the diffusion method useful for testing the effectiveness of biocides?].
AB  - The authors tested the fungicide effect of different biocides by the diffusion
      method. Its principle involves pipeting samples of the tested fungicide
      preparations into pits in an agar medium on Petri dishes. The agar is inoculated
      over the whole surface with spores of fungi. It is incubated at 28 degrees C for
      2 to 3 days. The size of the inhibition zones in the increments of fungi round
      the pits with the preparation are recorded. The authors discuss the suitability
      of this method for different types of preparations with regard to the results
      they assembled.

PMID- 11233673
TI  - [Analysis of the incidence of tularemia in the Breclav District 1994-1999].
AB  - Southern Moravia is one of the areas where there are long-term natural foci of
      tularaemia. In 1994 in the Breclav district an exacerbation of the disease was
      recorded in hares. During autumn hunts a positive reaction was recorded in 5.75%
      of examined hares. An elevated seropositivity persisted also in subsequent years
      and at the same time a higher human morbidity in the mentioned region. The
      objective of the investigation was to assess the causes and circumstances which
      led to the exacerbation of old known but in recent years quiescent foci in the
      mentioned region. To this end 350 small terrestrial mammals were examined. In one
      case it proved possible to detect the causal agent in Microtus arvalis. By
      examination of arthropods it proved possible to isolate 33 strains, i.e. 32
      strains from ticks Dermacentor reticulatus and one strain from Ixodes ricinus.
      The results of the examination revealed that tularaemia as a classical infection
      with a natural focus may persist in areas where there are prerequisites for
      survival of the causal agent in the environment. One of the important factors of
      the environment are susceptible individuals (hares, small terrestrial mammals) as
      well as blood sucking arthropods as vectors of the disease.

PMID- 11233674
TI  - Pathophysiology of epilepsy.
AB  - This work reviews the current knowledge on epileptogenesis and pathophysiology of
      epilepsy. Recently, gene defects underlying four monogenic epilepsies
      (generalized epilepsy with febrile seizures, autosomal dominant nocturnal frontal
      lobe epilepsy, benign familial neonatal convulsions and episodic ataxia type 1
      with partial seizures) have been identified, shedding new light on the
      pathophysiology of epilepsy as these diseases are caused by ion channel
      mutations. Although epileptic syndromes differ pathophysiologically, common
      ictogenesis-related characteristics as increased neuronal excitability and
      synchronicity are shared as well as mechanisms involved in interictal-ictal
      transition. Emerging insights point to alterations of synaptic functions and
      intrinsic properties of neurons as common mechanisms underlying
      hyperexcitability. This work also reviews the neurochemical mechanisms of
      epilepsy. An imbalance between glutamate and gamma-aminobutyric acid
      neurotransmitter systems can lead to hyperexcitability but catecholaminergic
      neurotransmitter systems and opioid peptides were shown to play a role in
      epileptogenesis as well. An overview of currently available anti-epileptic drugs
      and their presumed mechanisms of action is given as an illustration of the
      neurochemistry of epileptogenesis. Most anti-epileptic drugs exert their anti
      epileptic properties through only a few neurochemical mechanisms that are
      meanwhile basic pathophysiological mechanisms thought to cause seizures.

PMID- 11233675
TI  - Comparison of fluorine-18 deoxyglucose and O-15 water PET in temporal lobe
      epilepsy.
AB  - This study reports a comparison of Fluorine-18 deoxyglucose positron emission
      tomography (FDG-PET) and O-15 water (H2(15)O) PET with regard to lateralization
      of the seizure focus in patients with complex partial epilepsy. The analysis of
      35 patients who had an anterior temporal lobectomy for medically intractable
      seizures indicated that FDG- and H2(15)O-PET were highly correlated in
      demonstrating the epileptic focus. FDG- and H2(15)O-PET showed significant
      asymmetries in 83% and 77% of cases respectively. The lateralization with visual
      analysis of MRI was found to be lower than both FDG and blood flow imaging. Ictal
      electroencephalography (EEG) lateralizations were concordant with sites of blood
      flow and FDG-PET abnormalities. Thirty-three patients (94%) were seizure-free or
      improved significantly after surgery. In conclusion, blood flow PET yielded
      similar results compared to FDG-PET and can be a valuable modality in
      preoperative evaluation of patients with temporal lobe epilepsy.

PMID- 11233676
TI  - Coma induced by intoxication.
AB  - Clinicians in the emergency department are often confronted with coma patients
      due to poisoning. A systematic general approach involving early consultation with
      a neurologist is of paramount importance. A high index of suspicion, a systematic
      first assessment already in the prehospital phase and early stabilisation of
      vital functions are the essential first steps. Specific antidotes like hypertonic
      glucose and thiamine are part of a "coma cocktail". The opiate antagonist
      naloxone should be used only when clinically indicated and in a titrated way.
      Flumazenil should only be used with caution and in restricted cases. Clinical
      neurological evaluation and technical investigations like CT-scan and laboratory
      tests should make part of a careful diagnostic plan. Toxicological tests deserve
      their place in the diagnostic work up of a coma patient with suspected poisoning.
      Knowledge of the possibilities of the toxicology lab and optimal communication
      with the clinical toxicologist is important for optimal patient care.

PMID- 11233677
TI  - Therapeutic coma or neuroprotection by anaesthetics.
AB  - Some surgical patients are at an increased risk for developing cerebral
      ischaemia. A subset of these patients is believed to benefit from putative
      cerebroprotective effects of anaesthetic agents. Therefore, in this setting these
      drugs could have therapeutic modalities, besides their auxiliary functions to
      make surgery possible. However, both animal and especially human data are very
      disappointing. Only the barbiturates and isoflurane have an experimental record
      warranting further research to delineate proper indications for their use as
      neuroprotective agents in surgical patients.

PMID- 11233678
TI  - The usefulness of EEG, exogenous evoked potentials, and cognitive evoked
      potentials in the acute stage of post-anoxic and post-traumatic coma.
AB  - Three-modality evoked potentials (TMEPs) have been used for several years in
      association with the EEG as a diagnostic and prognostic tool in acute anoxic or
      traumatic coma. Cognitive EPs have been recently introduced. EEG and cognitive
      EPs provide functional assessment of the cerebral cortex. TMEP parameters can be
      described by two indices: the index of global cortical function (IGCF) and the
      index of brainstem conduction (IBSC). Although it remains a unique tool for
      epilepsy assessment, the value of EEG is largely limited by its high sensitivity
      to the electrical environmental noise, its dependence on sedative drugs, and its
      inability to test the brainstem. Major TMEP alterations (absence of cortical
      activities more than 24 hours after the onset of post-anoxic coma, major pontine
      involvement in head trauma) are associated in all cases with an ominous prognosis
      (death or vegetative state). However, even if mild TMEP changes are associated
      with a good prognosis in 65% (post-anoxic coma) to 90% (head trauma) of cases,
      some patients never recover despite exogenous TMEPs that are only mildly altered
      in the acute stage. Thus, cognitive EPs can usefully complement exogenous EPs as
      a prognostic tool in coma. Indeed, even if the absence of cognitive EPs in
      comatose patients does not have any prognostic value, their presence implies a
      very high (more than 90%) probability of consciousness recovery. The major
      technical challenge for the future will be the development of reliable tools for
      continuous EEG and TMEP monitoring.

PMID- 11233679
TI  - Thalamic hand dystonia: an MRI anatomoclinical study.
AB  - Focal dystonia has been attributed to lesions involving the basal ganglia and/or
      thalamus. Hand dystonia was studied in a patient with a unilateral thalamic
      infarction documented by MRI. A 18-year-old girl presented with severe isolated
      dystonia of the right hand as a sequel of perinatal infarction. MRI scan revealed
      infarction affecting part of the dorsomedian, lateral posterior, ventral lateral,
      ventral posterior lateral nuclei, and centromedian-parafascicular nucleus of the
      contralateral thalamus. The unique MRI anatomoclinical presentation of this case,
      taken together with the literature data, could provide evidence that a lesion
      affecting one or several thalamic nuclei, including the centromedian nucleus, can
      induce hand dystonia.

PMID- 11233681
TI  - Isolated sixth nerve palsy from pontine infarct.
AB  - Isolated sixth nerve palsy associated with pontine infarct is very rare due to
      close anatomic organization of the structures. A 62-year-old woman, who
      complained of diplopia, had a diagnosis of sixth nerve palsy. Ophthalmological
      examination revealed 30 PD left esotropia in primary position with limited
      abduction of the left eye. Neurologic examination was normal. MR showed a lacunar
      infarct in the pons consistent with a fascicular lesion. Cerebral angiography was
      normal. Pontine infarcts causing fascicular lesions should be kept in mind in
      isolated sixth nerve palsies.

PMID- 11233680
TI  - A "cortico-basal degeneration"-like syndrome as first sign of progressive
      multifocal leukoencephalopathy.
AB  - We report an unusual case of probable progressive multifocal leukoencephalopathy
      (PML), who initially presented with a right-sided movement disorder, including
      upper limb dystonia, tremor, and dyspraxia, reminiscent of corticobasal
      degeneration. In the further course, the patient developed disorientation,
      confusion, and bradyphrenia. The appearance of white matter MRI lesions as well
      as a positive PCR test result for JC-virus in the cerebrospinal fluid finally led
      to the correct diagnosis.

PMID- 11233682
TI  - Isolated nuclear oculomotor nerve syndrome due to mesencephalic hematoma.
AB  - Unilateral third nerve palsy with bilateral superior rectus paresis and bilateral
      ptosis is a typical condition for nuclear oculomotor nerve syndrome. We report a
      case of nuclear oculomotor nerve syndrome due to midbrain hemorrhage, as a rare
      cause. A 73-year-old man presented with an abrupt onset of double vision and
      difficulty opening his eyes. He had uncontrolled hypertension in his history.
      Neurological examination revealed right oculomotor palsy with impairment of
      bilateral upward gaze and bilateral ptosis. MRI showed a mesencephalic area of
      increased T1 signal and decreased T2 signal consistent with a subacute hematoma.
      It is emphasized that isolated mesencephalic hemorrhage may be the cause of the
      nuclear oculomotor nerve syndrome without associated neurological signs.

PMID- 11233683
TI  - A case of Adams-Oliver syndrome associated with acrania, microcephaly,
      hemiplegia, epilepsy, and mental retardation.
AB  - Adams-Oliver syndrome (AOS) is a rare congenital disorder, characterized by
      aplasia cutis congenita (ACC) of the scalp and variable degrees of terminal
      transverse limb defects. In this article, a newborn infant diagnosed as AOS for a
      large scalp defect, acrania, and finger malformations is presented. The patient
      was hospitalized and the scalp defect was successfully repaired with several
      surgical operations. During the hospitalization septicemia, meningitis, and
      convulsions developed, but they were successfully treated with appropriate
      antibiotics, antifungal, and anticonvulsive agents, He was discharged five months
      after admission to the hospital. Now, he is 3 years old, and has microcephaly,
      moderate mental retardation, left spastic hemiplegia, and epilepsy.

PMID- 11233684
TI  - The use of the Canadian occupational performance measure as an outcome of a pain
      management program.
AB  - The last three decades have seen the emergence of measures to assess the efficacy
      of pain management programs. Recently there has been interest in measures that
      assess clients' perceptions of their own performance. The Canadian Occupational
      Performance Measure (COPM) (Law et al, 1994, 1998) is an individualized measure
      designed for use by occupational therapists to detect a self-perceived change in
      occupational performance problems over time. It may be an important extra
      dimension to assessing the outcomes of pain management programs. The aim of this
      study was to ascertain the validity of the COPM as an outcome measure for the
      Liverpool Pain Management Program. One hundred and six clients were recruited to
      the study and 87 clients completed a battery of tests including the COPM at
      baseline, end of program and 3 month follow-up. Results of the study demonstrated
      that the COPM showed good evidence of concurrent criterion validity and
      sensitivity to change.

PMID- 11233685
TI  - Relationships among three clinical measures of muscle tone at the elbows of
      individuals after a stroke.
AB  - Patterns of associations among three common clinical muscle tone measures were
      investigated to determine their degree, and patterns of agreement. Data
      contributing to selection of clinical measures of muscle tone and understanding
      factors contributing to occupational dysfunctions were also sought. Forty five
      persons who were admitted after stroke to two occupational therapy rehabilitation
      programs were randomly selected. Their affected elbow's resting position (EJP),
      resistance to passive extension (ERM) and the angle where resistance first
      appeared (EAR) were measured by one, then a second therapist who also measured
      voluntary muscle function. Correlations among the three measures were calculated
      for both administrations and among patient subgroups with statistical correction
      for multiple correlations. Statistically significant associations appeared
      between ERM and EAR and between EJP and EAR. Highest statistically significant
      associations appeared among subjects with poor upper extremity function and those
      with low muscle tone. Patterns of associations were similar for the first and
      second administrations at both centres, though patterns among subgroups differed
      between centres. Correlation patterns suggest that biomechanical factors may
      influence the joint's resting position (EJP) more than ERM and EAR. Measures may
      be used interchangeably only with selected patient subgroups, which should also
      be the basis of method selection.

PMID- 11233686
TI  - Career choices: a comparison of two occupational therapy practice groups.
AB  - The increasing number of elderly people in the population and their greater use
      of the health care system require an increasing number of health care providers
      to work with older adults. A shortage of health care professionals to provide
      this care, as well as a reluctance to provide such care have been reported in the
      literature. The purpose of this qualitative study was to investigate how
      occupational therapists decide to work with older adults. Using a comparative
      approach, 40 occupational therapists were interviewed, 20 working in gerontology
      and 20 working in paediatrics. The findings indicate that social characteristics
      and experiences of the individual, as well as the context of work are important
      influences for practice choice decisions. Mapping of career paths led to the
      development of a typology to further describe the different influences involved
      in the career choices of these occupational therapists. Recommendations related
      to education and practice provide practical means by which to implement change.

PMID- 11233687
TI  - A functional model of cognitive rehabilitation in occupational therapy.
AB  - Persons who sustain cerebral injuries often have cognitive impairments.
      Occupational therapists are active in providing cognitive rehabilitation that
      aims to minimize the effects of cognitive deficits in their clients' lives. This
      paper presents a brief review of the literature in the area of cognitive
      rehabilitation including major characteristics of existing occupational therapy
      models related to the treatment of people who need cognitive rehabilitation. A
      model of cognitive rehabilitation is proposed that emphasizes functional
      components of occupational therapy in different rehabilitation settings. This
      model, called the Functional Model of Cognitive Rehabilitation, supports the use
      of activities in naturalistic settings in treatment, in order to enable those
      with cognitive impairments to fulfill their occupational roles.

PMID- 11233688
TI  - Clinical description of children with developmental coordination disorder.
AB  - Occupational therapists working within School Health Support Services are
      receiving increasing numbers of referrals, relative to past rates, for children
      who are experiencing motor problems and may have developmental coordination
      disorder. Based upon clinical experience, therapists indicate that these children
      are typically referred in the early school years and that most have handwriting
      difficulties; to date, however, there has been little empirical evidence to
      support these observations. In this paper, descriptive information is presented
      for 556 children who may be presumed to have developmental coordination disorder
      and who had been referred to school-based health services in two centres. Typical
      reasons for referral, co-morbidity information, and assessment practices are
      presented. Findings confirmed the presence of many occupational performance
      issues in this population, including handwriting difficulties, and challenge
      therapists to broaden the current scope of school health assessment and
      intervention practices.

PMID- 11233689
TI  - Occupational therapy practice patterns with older Swedish persons at home.
AB  - This paper explores and describes occupational therapy practice patterns during
      two periods for 89 elderly persons living at home. Occupational therapists
      working in one social welfare district in Stockholm, Sweden documented and
      reported every occupational therapy intervention provided. The results revealed
      that the elderly persons who received occupational therapy services during an
      extended period had an age span of 30 years, with a mean age over 80 years. They
      had several medical problems and were living in different types of settings.
      Occupational therapists provided a wide range of interventions, most frequently
      categorised as treatment, especially related to leisure activities. Irrespective
      of level of care, the median of interventions per person increased or was the
      same over time, and 72% of the elderly persons remained at the same level of
      care. Enabling occupation for elderly disabled person living in their home
      involves constantly adjusting to the current situation since the clients'
      capacities, goals and environment change over time. Therefore, occupational
      therapists need to have a client-centred approach working in home health
      community services.

PMID- 11233690
TI  - Detection and toxin production of Staphylococcus aureus in sudden infant death
      cases in Hungary.
AB  - The potential role of microbial agents was investigated in 13 cases of Sudden
      Infant Death Syndrome and in 9 non-SIDS cases in Budapest between September 1996
      and May 1998. Autopsy, histological examination and microbiological tests were
      performed on samples of blood, cerebrospinal fluid, pharyngeal samples and lung
      tissue from infants under one year died suddenly, without previous diseases. The
      multifactorial pathomechanism of SIDS was suggested by the isolation of toxin
      producing Staphylococcus aureus-, Enterobacteriaceae and Candida albicans strains
      in large number and by the detection of Parainfluenza Type 2 virus antigen. S.
      aureus proved the predominant bacteria in the SIDS cases. Nasopharyngeal
      microbial flora and S. aureus carrier of 100 age matched healthy infants were
      tested during the same period. S. aureus was isolated from 54% of SIDS cases and
      37% from healthy infants /OR = 1.986 (95% Confidence interval = 0.55-7.33), p =
      0243/. The enterotoxin and TSST-1 toxin producing activity of S. aureus showed
      the characteristic difference. The toxigenic S. aureus was detected in 46% of
      SIDS cases and 16% of healthy infants /OR = 4.5 (95% CI = 1.15-17.72), p =
      0.010/. The distribution of toxigenic and nontoxigenic isolates was 86% in SIDS
      cases and 43% in healthy infants /OR = 7.875 (CI = 0.78-191.89), p = 0.041/.

PMID- 11233691
TI  - Alternate adenovirus type-pairs for a possible circumvention of host immune
      response to recombinant adenovirus vectors.
AB  - With the help of monoclonal antibodies the existence of at least 18 different
      earlier not known intertype (IT) specific epitopes were demonstrated in different
      numbers and combinations on the hexons of different adenovirus serotypes. The IT
      specific epitopes play an important role in the experimental gene therapy and in
      the recombinant adenovirus vaccination because of the harmful immune response of
      the recipient organisms directed against the many different epitopes of the
      adenovirus vector. For the elimination of harmful effect the authors suggest the
      use of multiple vectors, each prepared from different adenovirus serotypes
      showing the loosest antigenic relationship to each other. The vectors would be
      used sequentially when second or multiple administration is needed. For this
      purpose the authors determined and described 31 such adenovirus type-pairs, which
      are probably the best alternates for sequential use in experimental gene therapy.

PMID- 11233692
TI  - Group-F streptococcal pleuro-pericarditis in a mesothelioma patient after dental
      surgery (case report).
AB  - A 71-year-old mesothelioma patient developed pleuro-pericarditis and pleural
      empyema. Bacteriological examinations and serological identification proved group
      F Streptococcus in the pleural fluid. Anamnestic data suggested that the source
      of infection might have been the oral cavity after dental surgery.

PMID- 11233693
TI  - The effect of Pygeum africanum on fibroblast growth factor (FGF) and transforming
      growth factor beta (TGF beta 1/LAP) expression in animal model.
AB  - On the basis of its fibroblast growth factor (FGF) inhibitory effect we assessed
      the possible inhibitory anti-inflammatory role of Pygeum Africanum extract
      (Tadenan) on FGF and transforming growth factor beta (TGF beta 1/LAP) expression
      of macrophages and neutrophils in broncho-alveolar lavage fluid (BAL) of rats in
      a bleomycin-induced acute inflammation model. The rats were divided into three
      groups: 17 untreated controls, 10 bleomycin-instilled rats, receiving NaCl
      (0.9%), and 10 rats receiving Pygeum Africanum extract. On the 12th (and 15th
      day) we performed BAL and after labelling of cells expression of FGF and TGF beta
      1 (LAP) was measured by flow-cytometry. We made a quantitative analysis of BAL
      cells as well. One-way ANOVA was used for statistical analysis. We found in
      Pygeum Africanum extract treated group 1, a significantly decreased number of
      neutrophil granulocytes (p < 0.05) compared with other groups 2, there was a
      considerable decrease (not significant) in expression of TGF beta 1(LAP) on BAL
      macrophages, but not in case of FGF. IN CONCLUSION: our results show the possible
      1. inhibitory effect of this drug on TGF beta 1 (LAP) expression, 2. anti
      inflammatory role on neutrophil granulocytes.

PMID- 11233694
TI  - Interaction of immunosuppressive drugs in mouse experiments with special regards
      to bacterial translocation.
AB  - Following intraperitoneally (i.p.) applied treatment with 12.5 mg/mouse
      prednisolonum (PRD) no bacterial translocation (BT) was observed in mice. The PRD
      treatment applied in combination with lymphotropic cytostatics as
      dianhydrogalactitol (30 mg/kg i.p.) or chlorpromazine (75 mg/kg i.p.) both
      causing BT, did not increase the mice's drug sensitivity to the used agents.
      According to our results, PRD can be suitable for combined application with other
      immunosuppressive agents as it can increase immunosuppression without increase of
      side-effects such as those induced by bacterial translocation.

PMID- 11233695
TI  - Fleroxacin uptake in ischaemic limb tissue.
AB  - Antibiotic application to patients with ischaemia of lower limbs may be indicated
      to avoid or treat infection of soft tissues. Fleroxacin, a fluoroquinolone,
      active against various Gram-negative and Gram-positive organisms may be used for
      this purpose. We evaluated the diffusion of fleroxacin into bone, subcutaneous
      fat, muscle and tendon tissues of lower limb tissue after a 400 mg i.v. dose.
      Concentrations in ischaemic tissues were similar to those found in non-ischaemic
      sites. Since the maximum antibiotic levels found were lower than the MICs of
      various pathogens relevant for infection, we suggest to increase the dose used
      for this peri-operative prophylaxis to 800 mg.

PMID- 11233696
TI  - The place of viruses in the "tree of life".
AB  - Ribozymal entry into vesicle containing autocatalytically replicating
      oligopeptides engendered RNA proliferation and enzyme synthesis within units
      whose RNA genomes derived from ancestors of viroids. There is good reason to
      consider the coexistence of proto- or spheroplastic forms of ancient prokaryotes
      and archaeons. Predecessors of extant mycoplasmavirus L3 or archaeal
      fuselloviruses could induce cell fusions among these entities. The possibility
      that the first eukaryotic cells arose consequentially to virally mediated fusions
      of prokaryotic and archaeal proto- or spheroplasts is presented. Retrotransposons
      and endogenous retroviruses might have emerged in theropod dinosaurs when Aves
      evolved; and directed the development of syncytiotrophoblasts in the placentae of
      the first mammals. As viruses coevolved with their hosts descendants of ancient
      viruses diverged from one another. Certain phenotypical features could connect
      extant phages and eukaryotic viruses to common ancestors.

PMID- 11233697
TI  - QSAR studies on antimalarial 2,4-diamino-6-quinazoline sulfonamides.
AB  - The present paper discusses QSAR studies on antimalarial 2,4-diamino-6
      quinazoline sulfonamide derivatives using electronic parameters, namely energy of
      highest occupied molecular orbitals (EH), energy of lowest unoccupied molecular
      orbitals (EL) and charge density (CD). The results have shown that better results
      are obtained by introducing dummy parameters (indicator parameter), Ip. Excellent
      results are obtained when all the four parameters (EH, EL, CD and Ip) are used in
      correlation analysis.

PMID- 11233698
TI  - Phytotoxicity of pathogenic fungi and their mycotoxins to cereal seedling
      viability.
AB  - Aspergillus flavus, Alternaria alternata and Fusarium oxysporum were found to be
      the pathogenic fungi mostly reducing cereal (barley, sorghum and wheat)
      seedlings. The pathogens have the ability to produce aflatoxin B1 and G1,
      diacetoxyscirpenol, kojic acid and tenuazonic acid that reduced seedling
      viability. The inhibition dose for 50% reduction (LD50) was recorded by
      aflatoxins at 0.83 mg L-1 for barley, 1.74 mg L-1 for wheat and 2.75 mg L-1 for
      sorghum. Diacetoxyscirpenol produced its inhibition at 1.26 mg L-1 for barley,
      3.98 mg L-1 for wheat and 10 mg L-1 for sorghum. Kojic acid induced 50%
      inhibition at 63 mg L-1 for barley, 105 mg L-1 for wheat and 251 mg L-1 for
      sorghum. However, tenuazonic acid was less toxic where, the toxicity was ranged
      between 79-550 mg L-1. The inhibition in germination was more pronounced in
      barley followed by wheat and negligible in sorghum to all tested mycotoxins. This
      inhibition attributed to the reduction in seedling amylase activity. Amylase was
      also reduced in the same trend: barley > wheat > sorghum. Grain treatment with
      carboxin-captan and thiophanatemethyl-thiram at 1 g kg-1 grain increased
      seedlings vigour of wheat in sterilized soil by 45 and 22%, barley by 24 and 33%
      and sorghum by 15 and 30%, respectively. These fungicides have also a positive
      effect on cereal when soil was inoculated with A. flavus, A. alternata and F.
      oxysporum.

PMID- 11233699
TI  - Xylanolytic activities of Streptomyces sp. 1--taxonomy, production, partial
      purification and utilization of agricultural wastes.
AB  - Twenty-four different strains of Streptomyces spp. isolated from Egyptian soil
      were tested for their ability to produce extracellular xylanases. Of all these
      isolates a Streptomyces sp. that had the highest potential for xylanolytic
      activity was chosen. From various morphological, physiological and antagonistic
      properties, this isolate was found to belong to Streptomyces lividans. Factors
      affecting xylanase production by this organism in a basal salt medium containing
      purified sugar-cane bagasse xylan as a sole carbon source were examined. A
      noticeable increase in enzyme activity was observed in the presence of peptone or
      soyabean meal. However, a slight increase was noticed with ammonium sulphate.
      Optimum production for xylanase was achieved after five days incubation on a
      rotary shaker (180 rpm) at 30 degrees C. The initial pH values were around
      neutrality. In addition, this organism has high potential for xylanolytic
      activity when grown on lignocellulosic wastes including corn cobs, wheat bran,
      peanut shells, sawdust, wheat straw and sugar-cane-bagasse. Partial purification
      of the enzyme in the culture supernatant was achieved by salting out at 50-80%
      ammonium sulphate saturation with a purification of 9.03-fold and 57.9% recovery.

PMID- 11233700
TI  - Enzymes of Candida albicans cell-wall lytic system produced by Streptomyces
      thermodiastaticus.
AB  - The production of the enzymes of Candida albicans cell-wall lytic system by S.
      thermodiastaticus was found to be affected by some growth conditions and
      nutritional factors. The highest lytic activity was obtained after 18 h of
      incubation at pH 5.5 and an incubation temperature of 50 degrees C. The carbon
      source influenced the production of the enzymes of the yeast cell wall lytic
      system. Maximum lytic activity was obtained when Candida albicans cell-wall (1
      g/100 ml) was used as the sole carbon source. NaNO3 at 0.1 g/100 ml level was the
      best nitrogen source for the biosynthesis of the enzymes of the yeast lytic
      system. From all phosphor sources, microelements, and growth factors tested,
      KH2PO4 (1 g/l), ZnSO4 (1 mg/l) and Tween 80 (0.1%), respectively were found to
      favour highest enzymes production of the lytic system. The Candida albicans cell
      wall lytic system produced by S. thermodiastaticus mainly contained chitinolytic
      and proteolytic activities.

PMID- 11233701
TI  - Production of thaxtomin a by two species of Streptomyces causing potato scab.
AB  - A total of nine isolates of streptomycetes were isolated from scab lesions on
      potato tubers. Five out of them were pathogenic on potato minitubers and four of
      the pathogenic isolates produced thaxtomin A in infected tubers tissues. The
      lesion surface areas induced by thaxtomin A were highest in treatment of the
      minitubers with extract of OMB inoculated with S-6 and S-7, intermediate with
      that inoculated with S-4 and lowest with S-3. The pathogenic isolates were
      identified by their colour of aerial mycelia, melanin pigment productivity (+ or 
      ), the type of spore chains morphology and carbon utilization as either S.
      scabies strains S-3, S-4 and S-8, or S. acidiscabies strains S-6 and S-7. S-3 and
      S-4 produced 0.65 and 1.60 micrograms thaxtomin A per milliliter of OMB,
      respectively, whereas S-6 and S-7 produced similar amounts of thaxtomin A, 2.36
      and 2.10 micrograms per ml of OMB, respectively. The optimal temperature for
      production of thaxtomin A by S. scabies and S. acidiscabies was 28 degrees C.
      Production of thaxtomin A by S. scabies strain S-4 and S. acidiscabies strain S-6
      was suppressed at least 50-fold at 0.5 and 0.3% of glucose, respectively.
      Fructose enhanced the production of thaxtomin A by both S. scabies and S.
      acidiscabies.

PMID- 11233702
TI  - Cigarette smoke decreases the expression of secretory component in human
      bronchial epithelial cells, in vitro.
AB  - Epithelial secretory component (SC) is thought to be essential for immunologic
      protection of the respiratory tract from viral and bacterial infection, since it
      transports polymeric IgA from the basolateral to the luminal surface of
      epithelial cells. We have hypothesized that recurrent infection in airways of
      cigarette smokers is at least partly a consequence of cigarette smoke-induced
      downregulation of the expression and/or release of SC from airway epithelial
      cells, subsequently resulting in decreased transcytosis of secretory IgA to the
      airway lumen. To test this hypothesis, we have cultured human bronchial
      epithelial cells (HBEC) from surgical tissues and exposed these for 20 minutes to
      either air or cigarette smoke. Following exposure to cigarette smoke the HBEC
      cultures were incubated for a further period of up to 24 h, during which time
      separate cultures were processed by immunocytochemistry for the presence of SC,
      in a time-dependent manner. The stained HBEC cultures were evaluated by colour
      image analysis for the percentage of total cells staining for SC. Exposure to
      cigarette smoke significantly decreased the percentage of total HBEC staining for
      secretory component from a baseline value (median and interquartile[IQ]1, IQ3) of
      35.9% (26.5, 41.6) to 15.7% (8.2, 25.4; p < 0.05) 1 h after exposure, compared
      with exposure to air. The percentage of cells staining for secretory component
      were further reduced to 5.3% (3.3, 6.4; p < 0.01), 6 h after exposure, compared
      to exposure to air. After incubation for 24 h following exposure to cigarette
      smoke, there was gross cell damage and the cells were not suitable for
      immunocytochemical analysis. These results suggest that short-term exposure to
      cigarette smoke may compromise the immune barrier function of the airway mucosa
      by decreasing the expression and/or release of epithelial SC, thereby decreasing
      the transcytosis of IgA necessary for inactivating the microbial pathogens in the
      airway lumen.

PMID- 11233704
TI  - [Nasal comfort and Cottle septoplasty. Prospective acoustic rhinometry study
      apropos of 102 cases].
AB  - Between june 1997 and september 1998, we have prospectively studied a cohort of
      102 patients who were referred to ENT consultation. All patients suffered a
      septal deviation and a syndrome that we call "morphological". All were operated
      on following the Cottle's septoplasty technique. At pre- and postoperative
      consultation, patients were asked to answer a questionnaire and a functional
      evaluation of the nasal air flow was assessed by acoustic rhinometry. We have
      described a nasal comfort grading that we compare with the objective results as
      assessed by acoustic rhinometry. Our study did not permit us to find any
      correlation between nasal comfort and minimal cross sectional area (MCA). But
      evaluation of the MCA was disturbed by several methodological artifacts. A
      statistical correlation between the nasal comfort grading and nasal volume in the
      side of the septal deviation was found. The acoustic rhinometry evaluation
      elicited two essential observations: the first is the increase of nasal fossae
      volume of 30% (and, at least, 26% of the MCA). The other is a relative decrease
      of 45% of nasal mucosa congestion. This study shows that the nasal septum has an
      essential function in the pathogenesis of the so-called "morphological"
      functional syndrome. The morphological correction obtained by the Cottle's
      septoplasty acts upon the nasal vasomotricity in decreasing nasal mucosa
      congestion and avoid a surgical reduction of the inferior turbinate.

PMID- 11233703
TI  - The spread and antibiotic resistance of Salmonella enterica serotype typhimurium
      DT104 in Hungary.
AB  - Comparison of phage types (PTs) determined by Felix and Callow's and Anderson's
      methods was performed testing 99 human strains of S. enterica serotype
      Typhimurium (S. typhimurium) isolated in Hungary. PT2 and PT2c--according to
      Felix-Callow--corresponded with Anderson's DT104 in case of 39 strains out of 40.
      Among 59 isolates belonging to other Felix-Callow's PTs only one strain was found
      which was DT 104. Similar unambiguous equalities could not be established between
      any other PTs comparing the two methods. The PTs of 17,877 human strains isolated
      between 1988 and 1999 were determined using Felix-Callow's method. On the basis
      of the above equality the emergence of DT104 could be followed retrospectively by
      means of the rate of PT2 and PT2c. The increase of DT104 began already in 1989,
      emerging first PT2c then PT2. It predominated since 1991 and it reached its
      maximum (78.3%) in 1999. The incidence of multiresistance among one of the groups
      of DT104 strains (Felix-Callow's PT2) was significantly higher in 1998 than the
      average of non-DT104 strains. The predominant R-type was ACST.

PMID- 11233705
TI  - [Olfactory esthesioneuromas].
AB  - Olfactory neuroblastomas are rare malignant tumours of the nose arising from the
      olfactory epithelium. In a retrospective series of 18 cases and a review of the
      literature, the authors establish the main features of this tumour. They
      emphasise the difficulties of histological examination, often requiring immuno
      cyt-chemistery and electron microscopy. They point out the value of a new
      classification, and confirm treatments being radio-surgical, with use of the
      combined rhino-neurosurgical approach when there is extension to the cribriform
      plate. They report a 5-year survival of 91.5%, with 87.5% at 10 years. The high
      incidence of lymph gland metastases (16.6%) is greater than that of local
      recurrence (11%) especially in the more advanced cases. The question of
      prophylactic treatment of the neck nodes is one to be considered.

PMID- 11233706
TI  - [Acute rhinosinusitis in the adult: national survey of general practice
      management].
AB  - Between the 17/1/2000 and the 31/3/2000 a study was carried out in 5000 general
      practitioners in the management of patients with acute maxillary sinusitis. The
      general practitioners filled out a questionnaire in 2 parts: the first part about
      their management (diagnosis-treatment) and the second part included 1 case study.
      According to the results of the first part, acute maxillary sinusitis occurred
      frequently during the winter months adding further complications. The second part
      of the study confirmed the finding of the first part. Analysis of case study
      demonstrates that this pathology affected men at the median age 37.6. The
      incidence of bilateral sinusitis is (61.4%) maxillary (61.1%), frontal (31.7%),
      ethmoidomaxillary (9.4%) or sphenoidal (1.7%). One quarter of patients
      participated in further medical investigations that included regular X rays of
      sinus and 14% patients in anterior rhinoscopy. In the older patients, on the
      patients with unilateral sinusitis, or sphenoidal sinusitis, the investigations
      were more frequent and these patients appealed for the specialist frequently (Ear
      Nose and Throat specialist mainly). The first line of treatment included 3.2
      products of which antibiotics 98.5%, vasoconstrictors 55%, anti-inflammatory 55%
      (corticosteroids 46.8%, non corticosteroids 8.7%), mucolytics 41.6%. In total,
      general practitioners confirmed their pragmatic management in the treatment of
      acute sinusitis based on clinical diagnosis.

PMID- 11233707
TI  - [Malignant melanoma of the nasosinal mucosa. Retrospective study apropos of 20
      cases].
AB  - Twenty patients were treated for malignant melanoma (MM) of the mucosal surfaces
      of the nose and sinuses between 1987 and 1999 in our department. The mean age of
      these patients was 64 years, and there were 11 females and 9 males (sex ratio
      1.2). Two patients had a past history of cutaneous or choroidal malignant
      melanoma, and were considered as having secondary melanoma. All patients
      presented with nasal obstruction and/or recurrent epistaxis. None of the patients
      with primary MM had either lymphadenopathy or distant metastases. 17 patients
      were treated surgically by the transfacial approach, aiming to obtain a cure.
      Radiotherapy and chemiotherapy were given only to the patients with secondary MM.
      Six patients have since presented with single or multiple local recurrence, and
      nine had distant metastases. The 3-year survival rate was 60%. This retrospective
      study has allowed us to compare the results of our series with these in the
      literature, and to review the treatment of this rare condition.

PMID- 11233708
TI  - [Endonasal surgery: results of surgery of ethmoido-frontal mucoceles].
AB  - The intranasal approach for mucoceles of the sinuses represents an advance in the
      techniques of sinus surgery. The object of our study is to show the value of this
      type of surgery by reviewing 16 cases of fronto-ethmoidal mucoceles undergoing
      surgery in our department. The approach was purely intranasal. Surgery consisted
      of wide marsupialisation of the nasal cavities. The immediate postoperative
      progress was good. There were no complication in this series; neither was there
      any recurrence. The follow up period was from 3 months to 5 years. As the follow
      up period was too short in some of the cases, no firm conclusions can be drawn.
      Yet despite this limitation, it seems that the intranasal approach is to be
      preferred in dealing with mucoceles of the sinuses.

PMID- 11233709
TI  - [Massive lytic osteodystrophy or Gorham-Stout disease of the craniomaxillofacial
      area].
AB  - Gorham's disease also called idiopathic massive osteolysis represents a rare
      affection with unknown aetiology. This disease was described in different bones
      of the body but its location on maxillo-facial skeleton is particular by the
      number of cases in the world (only 32), by morphological, functional consequences
      and the prognosis. The authors describe a new case of male teenager (17 years
      old) who had a massive osteolysis of mandibular ramus, upper maxillary, malaire,
      sphenoid, temporal and occipital left bone. The authors give precision about
      epidemiological data, methods of diagnosis and therapeutic procedures.

PMID- 11233710
TI  - [Farber disease: a cause of hoarseness of the voice in children].
AB  - Farber's disease (disseminated lipogranulomatosis) is an autosomal recessive
      disease characterized by deposition of glycolipid ceramide in different tissues
      due to deficiency of lysosomal acid ceramidase. The disease starts to manifest at
      the age of four months by a hoarse cry or swollen tender joints followed by
      subcutaneous nodules. This disease is fatal in the first years of life and no
      treatment is known until now. This study presents four cases of Farber's disease
      who all presented by hoarseness of voice, polyarthritis and subcutaneous nodules.
      After clinical examination, the diagnosis was confirmed by fiberoptic flexible
      nasopharyngolaryngoscopy which showed the presence of vocal folds thickening in
      all patients and affection of the cricoarytenoid joint in one patient and biopsy
      from the subcutaneous nodules which showed infiltration of the deep dermis and
      subcutaneous tissues by fibroblasts and large foamy histiocytes.

PMID- 11233711
TI  - [Hypopharyngeal foreign body migration. Apropos of 2 pediatric cases].
AB  - Two children cases report of an ingested fish bone perforating upper digestive
      tract lumen and completely migrating to the retropharyngeal space in the neck are
      presented. It is an unusual presentation and we describe our management. In one
      case it was necessary to performed a cervicotomy to remove the foreign body. In
      other case the rigid endoscopy could remove the fish bone with forceps under
      direct vision. The literature is reviewed to improve the early recognition and
      treatment for these migrating foreign bodies.

PMID- 11233712
TI  - [Acceptability of local treatment of allergic rhinitis with a combination of a
      corticoid (beclomethasone) and an antihistaminic (azelastine)].
AB  - A prospective multicentre study involving 219 patients with seasonal or aperiodic
      rhinitis was performed to assess the acceptability of a local treatment combining
      antihistamine (azelastine) and corticoid (beclomethasone) drugs. The drugs were
      administered either together (morning and evening, with a 5-minute interval) or
      separately (azelastine in the morning and evening, and beclomethasone later
      during the morning and in the afternoon) for 15 days. Treatment acceptability was
      measured by a nine-fold questionnaire (7-point scale, mean score per question).
      Patient participation, protocol and therapy compliance, and treatment efficacy
      and tolerance were also studied. The acceptability of the association was
      satisfactory (mean score for general facility of treatment: 4.7/6) and did not
      differ between administration schedules. Patients found treatment easy, and were
      not bothered by the bulk of the bottles or the risk of mixing them up. This
      acceptability was confirmed by the low percentage (4%) of patients refusing to be
      included in the study (refusing any treatment by nasal spray). The general
      acceptability was confirmed by the results for therapy compliance, general
      efficacy and tolerance: 94.9% of the patients took more than 75% of the
      administrations prescribed, 77.6% of the patients and 85.2% of the practitioners
      judged treatment efficacy as good or excellent, and 84.6% of the patients and
      91.4% of the practitioners judged tolerance as good or excellent. Moreover, most
      of the adverse events consisted of minor signs of local intolerance, and were
      identical to those observed when the two treatments were administered alone.

PMID- 11233714
TI  - Presentation of cutaneous mastocytosis in 173 children.
AB  - This is a retrospective review of the case files and clinical photographs of 173
      children diagnosed with cutaneous mastocytosis by a dermatologist in an
      exclusively paediatric practice. Of the 98 males and 75 females, 51% had
      mastocytomas, 47% had urticaria pigmentosa and three patients had diffuse
      cutaneous mastocytosis. Of these cases, 87% first appeared prior to or at 6
      months of age. Flushing occurred in 26% of urticaria pigmentosa cases, 29% of
      mastocytomas and 100% of diffuse cutaneous mastocytosis. Blistering was noted in
      23% of urticaria pigmentosa, 31% of mastocytomas and 100% of diffuse cases.
      Neither symptom was noted in 59% of urticaria pigmentosa and 49% of mastocytomas.
      There were three cases with a positive family history. The finding of a palmar
      mastocytoma has only once been previously reported. Illustrated descriptions of
      our cases are provided.

PMID- 11233713
TI  - Occupational skin disease in hairdressers.
AB  - Hairdressers belong to an occupational group that is commonly affected by
      occupational skin disease, specifically contact dermatitis, which may be allergic
      or irritant and, less commonly, contact urticaria. Occupational contact
      dermatitis predominantly affects apprentices, and atopy is a recognized risk
      factor associated with a poor prognosis. Repetitive wet work leading to irritant
      contact dermatitis, followed by exposure to allergens and the development of
      allergic contact dermatitis, are the main factors contributing to occupational
      contact dermatitis. Once developed, it is often difficult to manage and is a
      cause of significant morbidity. Early education, training and prevention is the
      best approach to the management of this disorder that is endemic among
      hairdressers.

PMID- 11233715
TI  - Dermatomyofibroma: a report of two cases, one occurring in a child.
AB  - Dermatomyofibroma is a recently described plaque-like dermal tumour composed of
      myofibroblasts that usually presents around the shoulder, axilla and posterior
      neck, often in young adult females. Here, we present two cases, one from the
      posterior axilla of a 33-year-old female and one from the posterior neck of a 7
      year-old male. Both were clinically red-brown lesions with histological and
      immunohistochemical features diagnostic of dermatomyofibroma. There was no
      evidence of aggressive biologic behaviour with 3 months and 2 months follow up,
      respectively. While the majority of dermatomyofibromas present in postpubescent
      females, the 7-year-old male exemplifies a subgroup occurring in male children
      which appears to show a particular predilection for the posterior neck.

PMID- 11233716
TI  - Mycobacterium abscessus wound infection.
AB  - We report an isolated case of wound infection due to Mycobacterium abscessus
      following minor cutaneous surgery. The patient had routine skin cancer surgery in
      a private dermatology practice setting. He presented 2 weeks later with a wound
      infection which failed to respond to cephalexin. The patient reported that he had
      walked through salt water and bushes with exposed surgical wounds 1 week
      postoperatively. Tissue cultures later grew M. abscessus. The patient was
      successfully treated with oral clarithromycin 500 mg qid of 6 months duration.

PMID- 11233717
TI  - Lip cancer: important management issues.
AB  - Lip cancer should be diagnosed and treated at an early stage. It most often
      presents on the lower lip of middle-aged to elderly males. The aetiology is
      similar to non-melanoma skin cancer, that is, chronic sun exposure. Despite
      treatment, a proportion of patients will experience delayed relapse and one in 10
      will die from lip cancer. Clinicians need to be aware of the natural history of
      this disease. Two cases of squamous cell carcinoma of the lip treated by
      radiotherapy are presented and discussed to highlight important aspects in the
      management of lip cancer.

PMID- 11233718
TI  - Allergic contact dermatitis due to benzalkonium chloride in plaster of Paris.
AB  - Plaster of Paris (POP) bandages are extensively used for splinting and casting
      injured or surgically repaired body parts. Allergic contact dermatitis caused by
      POP has been reported only rarely in the medical literature. An 81-year-old woman
      developed multiple large, tense, haemorrhagic bullae on the palm, and an acute
      vesicular eczematous eruption on the forearm, after the application of a POP
      splint. Subsequent patch testing revealed positive reactions to both the POP
      bandage used and to benzalkonium chloride, a component of the POP formulation.
      Patch tests to two other POP products without benzalkonium chloride were
      negative. These results confirm those of previous studies which have implicated
      the quaternary ammonium compound benzalkonium chloride as the allergen
      responsible for POP-induced allergic contact dermatitis.

PMID- 11233719
TI  - Generalized eczematous reaction to budesonide in a nasal spray with cross
      reactivity to triamcinolone.
AB  - A 78-year-old woman suffered a generalized eczematous hypersensitivity reaction
      following the use of an intranasal budesonide inhaler. Patch testing demonstrated
      positive reactions to both budesonide and triamcinolone. Her eczema responded to
      emollients, betamethasone dipropionate ointment and cessation of her intranasal
      budesonide inhaler.

PMID- 11233720
TI  - Severe cyclical thrombocytopenia in a patient with a large lymphatic-venous
      malformation: a potential association?
AB  - The case is reported of an infant who had a large vascular malformation involving
      his left arm and axilla. It was initially believed to be purely lymphatic in
      composition but some venous elements were identified subsequently, at operation.
      The lesion was unusual in that there was a total absence of skin over one area of
      it at birth, that it underwent spontaneous shrinkage in the early weeks of life,
      and that a circumferential scarring developed which led to severe functional
      disability of the limb. At 12 months of age the patient developed a profound
      cyclic thrombocytopenia that spontaneously resolved after 1 year. The cause of
      the platelet cycling is unresolved but might have been secondary to intermittent
      production by the malformation of a cytokine which was destructive against the
      platelets.

PMID- 11233721
TI  - Cheilitis caused by contact urticaria to mint flavoured toothpaste.
AB  - A 26-year-old woman presented with a 12-month history of persistent dermatitis of
      the lips. She had failed to respond to cosmetic avoidance and therapeutic
      measures. Patch testing was negative, including her toothpaste and toothpaste
      flavours. She defied diagnosis until an acute flare followed immediately after
      dental treatment with a mint flavoured tooth cleaning powder. This led us to
      prick test her to mint leaves and this was positive. Her cheilitis settled after
      changing from her mint-flavoured toothpaste. A diagnosis of contact urticaria
      should be considered in cases of cheilitis of unknown cause.

PMID- 11233722
TI  - Cutaneous alternariosis in a cardiac transplant recipient.
AB  - A 55-year-old male cardiac transplant recipient presented with cutaneous nodules
      on the limbs caused by Alternaria alternata. Oral fluconazole 200 mg daily for 3
      weeks was ineffective. Itraconazole 100 mg oral daily was ceased when
      hyperglycaemia developed. Individual lesions were successfully treated with
      either curettage and cautery or double freeze-thaw cryotherapy. Alternaria spp.
      are ubiquitous fungal saprophytes which may cause cutaneous infections
      particularly in immunocompromised patients.

PMID- 11233723
TI  - Mid-dermal elastophagocytosis presenting as a persistent reticulate erythema.
AB  - Two men are presented with a widespread persistent reticulate erythema
      concentrated within the chronically sun-damaged skin on their trunk. A fine
      papular element was present in one case and both lacked annular lesions. One
      patient was human immunodeficiency virus positive. Multiple skin biopsies showed
      an interstitial infiltrate of histiocytes containing multiple elastic fibres in
      the upper dermis. There was scant perivascular lymphocytic inflammation but no
      evident necrobiosis or palisaded granulomas seen typically with granuloma
      annulare. Elastic stains showed focal mid-dermal elastolysis. Diffuse reticulate
      erythema in sun-damaged skin may be a clinical marker for elastophagocytosis.
      This presentation differs from that previously described with actinic granuloma,
      diffuse granuloma annulare or the inflammatory phase of mid-dermal elastolysis
      and expands the clinical spectrum of this phenomenon.

PMID- 11233724
TI  - Amyloidosis of the tongue with kappa light chain disease.
AB  - A 70-year-old woman presented with a painful, red tongue with papules associated
      with xerostomia and systemic symptoms including weight loss, difficulty in
      swallowing and breathing, haemochezia and leg swelling. Biopsy from the tongue
      demonstrated amyloid deposits and, on further investigation, kappa chain disease
      was diagnosed. Primary systemic amyloidosis was diagnosed and the patient died
      within weeks of presentation.

PMID- 11233725
TI  - Pseudomonas aeruginosa infection mimicking erythema annulare centrifugum.
AB  - A 3-year-old girl receiving chemotherapy for acute lymphocytic leukaemia
      developed a rapidly expanding red annular plaque on her thigh, initially without
      signs of systemic toxicity or local pain. Subsequently she developed Pseudomonas
      aeruginosa sepsis and purpura at the leading edge of the plaque. Skin biopsy
      showed an extensive necrotizing vasculitis with numerous Gram-negative bacilli in
      the blood vessel walls. In immunocompromised individuals, skin biopsy and culture
      of cutaneous lesions for bacteria and fungi should be considered even in the
      absence of signs of systemic toxicity or multiple lesions.

PMID- 11233726
TI  - Phenolic ablation of the nail matrix.
AB  - Therapeutic ablation of nail is necessary in a variety of settings. The challenge
      is to achieve destruction of nail matrix with minimal pain and to ensure that
      there is no re-growth of nail. There are many different methods of nail ablation,
      with excisional surgery and phenolic ablation of matrix representing the most
      common. The balance of published data favours phenolic ablation as a simple
      procedure with low morbidity and the least chance of recurrence.

PMID- 11233727
TI  - Multiple corticosteroid allergies.
AB  - A case of vulval dermatitis and perioral dermatitis due to contact allergy to
      multiple class D corticosteroids, mometasone furoate and methylprednisolone
      aceponate is presented. Patch testing with commercially available corticosteroid
      creams is a simple and useful diagnostic test. Beware of delayed positive
      reaction, seen on day 8 of the repeat open application test on this patient.

PMID- 11233728
TI  - Expansion techniques after Mohs' surgery on the face.
AB  - Mohs' surgery in the face has established itself as the optimal technique for a
      high cure rate of basal cell and squamous cell carcinoma occurring in the skin of
      the face. However, after the resection in Mohs' surgery, the defects, when
      extensive, require careful, planned reconstruction in order to produce a good
      cosmetic result. Although flap reconstruction is available for smaller lesions,
      larger defects can be covered often by expansion techniques. The expansion
      technique involves placing a silastic expander of various size and designs
      underneath the adjacent skin and, over a period of weeks, injecting saline into
      the expander in order to increase the amount of skin available for future flap
      reconstruction. This usually represents a two-stage procedure consisting of the
      insertion of the expander and, some weeks later, removal of the filled expander
      when there is sufficient tissue, and using this tissue to reconstruct the initial
      Mohs' defect by a flap. When defects are greater than half the aesthetic unit of
      the face, or greater than one-third in the forehead, or over 6 cm in the scalp,
      expansion techniques should be considered for reconstruction.

PMID- 11233729
TI  - [Postoperative monitoring of free fibular grafts by dynamic magnetic resonance
      imaging. Preliminary results in three cases of mandibular reconstruction].
AB  - The vascularized free fibular graft has been used in mandibular reconstructive
      surgery since 1975. This technique has been progressively developed, and it is
      now the procedure of choice for mandibular reconstruction although in certain
      postoperative circumstances it can be difficult if not impossible to monitor bone
      vitality. However, bone vascularization can be detected by dynamic magnetic
      resonance imaging (MRI), as this technique has been experimentally and clinically
      validated in the early diagnosis of osteonecrosis. The aim of this study was to
      evaluate the efficacy of MRI for the postoperative monitoring of vascularized
      free fibular grafts in human mandibular reconstruction. Dynamic contrast-enhanced
      MRI was used to study the variation in contrast over time following injection of
      gadolinium contrast medium, and to evaluate the degree of bone marrow perfusion
      of the fibular graft. This variation in signal intensity was visualized in the
      form of a curve, i.e., a perfusion curve for the bone marrow region. An
      examination was performed in three patients at different postoperative times and
      under different conditions. In one case, MRI confirmed the presence of fibula
      blood supply in spite of the necrosis of the adjacent fascio-adipose layer. In
      this article, the methodological difficulties have been discussed, particularly
      as regards data processing, and the present results have been compared with the
      findings in the literature. Dynamic MRI is a simple, reliable, non-invasive
      technique and its use in the postoperative monitoring of bone marrow perfusion
      and vascularized free fibular grafts permits a determination of the status of the
      latter following surgery, i.e., whether there is an adequate blood supply or not.

PMID- 11233730
TI  - [Antecubital flap: advantages in elbow coverage. An anatomical study and
      experience of five clinical cases].
AB  - The antecubital flap is a fasciocutaneous strip that has its blood supply
      provided by the first proximal collateral of the radial artery. This flap was
      described for the first time in 1983 by Lamberty and Cormack, but it has not been
      widely used and there have been only a few reports in the literature concerning
      this procedure. The aim of the present investigation was to demonstrate via an
      anatomical study and a report on five cases the viability of the various
      anatomical features of this cutaneous flap, and also its positive contribution to
      elbow reconstruction. The anatomical study involved eight fresh cadavers (eight
      upper limbs). An injection of colored prevulcanized latex was made in the humeral
      artery in the lower third of the arm. The aim was to determine which artery
      provided blood supply to the flap, its anatomical location, and also to look for
      possible distal anastomoses which would permit a distal pedicled flap to be
      removed. Contrary to the findings of other authors, in the present study it was
      found that the vessel providing blood to the antecubital flap always branched off
      from the radial artery. However, no anastomoses with distal vascularization were
      detected, which would have permitted a distal pedicled flap to be obtained. The
      use of the antecubital flap for elbow coverage was then illustrated by five
      clinical cases of soft tissue defects of the elbow. This method was found to be
      reliable, practical, and the flap could be rapidly dissected. Moreover, this
      particular technique is sensitive, and has an interesting rotational arc. The
      distal cutaneous island flap has the advantage of limiting scar tissue. A
      comparison between the antecubital flap and other pedicled flaps has then been
      made. In conclusion, it appears that this little-known procedure has definite
      advantages, and that it should be included in the range of surgical techniques
      that are available for soft tissue reconstruction in the case of elbow defects.

PMID- 11233731
TI  - [A scanning electron microscopy study of the surface of porous-textured breast
      implants and their capsules. Description of the "velcro" effect of porous
      textured breast prostheses].
AB  - The efficacy of breast prosthesis texturing in the prevention of capsular
      contracture has been established for about 20 years. This successful procedure
      has led to the development and marketing of a number of different models. In the
      present study, four porous-textured breast prostheses have been examined: the
      Arion monoblock implant, the CUI (McGahn), the Biocell (Mcgahn), and the Sebbin
      LS21. Scanning electron microscopic (SEM) investigation of the implant surfaces
      of the different prostheses was carried out on new samples received from the
      manufacturers. During a prospective study on eight patients, capsule samples
      corresponding to the four above-mentioned prostheses were taken to determine
      whether a secondary intervention was necessary for correction of asymmetry or
      malpositioning. These samples were analyzed by SEM to investigate whether there
      could be a correlation between prosthesis texturing and the aspect of the
      corresponding capsules. Significant ultrastructural differences were found
      between the various prostheses examined: the results showed that only the CUI and
      Biocell prostheses presented a mirror image of the capsule texturing, with a
      correspondence between the depressions on the prosthesis and the contacts on the
      capsule. This finding seems to be linked to the existence of a critical size for
      the pores that constitute the implant surface. This observation led to the
      hypothesis of an adhesive "velcro" effect between the prosthesis and its capsule.
      Although the latter may not be directly linked to the prevention of capsular
      contracture it can, however, have a major effect on implant stabilization in
      cases of primary breast reconstruction and in possible secondary adjustments of
      asymmetry and malpositioning.

PMID- 11233732
TI  - [Arguments in favor of adipocyte grafts with the S.R. Coleman technique].
AB  - The main criticism against fat reinjection procedures is related to whether it is
      possible to graft adipocytes or not. The ideal solution would be to perform
      biopsies a few months after the operation to check the evolution of the grafted
      tissue, but such an approach would be difficult to accept for our patients. To
      overcome this difficulty the authors have compiled all the arguments that plead
      in favor of adipocyte grafts when Coleman's technique is used. Peer demonstrated
      in animal studies that it is possible to graft fatty tissue and that more
      resorption occurs when the fragments are large in size. The histologic studies
      have shown that the different stages of Coleman's technique do not alter the
      viability of the adipocytes. A disorganization of the architecture of the lobules
      is observed, but this does not compromise the theory of adipocyte grafting. An
      MRI study, performed on ten patients, demonstrated that the reinjected fat cells
      persist several months after the procedure. These fat cells presented the same
      characteristics as the patient's native fat in the surrounding area. This
      impression was confirmed by histological analysis of the reinjected fatty tissue
      18 months after the graft. Finally, the clinical results obtained on over 200
      patients treated for various indications in plastic and cosmetic surgery lead us
      to believe that it is possible to perform grafts of fatty tissue.

PMID- 11233733
TI  - [A simple and effective technique for reconstructive surgery of medium-sized
      scalp defects].
AB  - From June to December 1999, eight patients aged from 16 to 30 years with scalp
      defects ranging from 9-11 cm in the tonsural region secondary to high-voltage
      electrical burns underwent scalp reconstruction via a technique based on the
      Orticochea method, but which was less complicated in design, easier to carry out,
      and also more efficient. The entire scalp was prepared for surgery subgalea, but
      in no case was the dura mater exposed. Then four local flaps were taken, i.e.,
      two temporal, one frontal, and one occipital flap. The width of each flap was the
      same size as the diameter of the scalp defect, and the base of each flap included
      the main regional blood vessels: A straight-forward advancement technique for the
      four flaps was not sufficient to completely cover such scalp defects, and a
      rotational approach was also introduced. In fact, the originality of the
      presently-described technique lies in the rotational approach, which is extremely
      efficient. It is carried out via three backcuts, beginning with the first
      temporal flap, then the second temporal flap, and if necessary the occipital
      flap; but never the frontal flap. These backcuts are performed in such a way that
      they are subsequently hidden by hair growth. In the present study, no skin graft
      was necessary, and no complications were reported. All the patients were
      satisfied with the results of surgery, both as regards the cosmetic aspect and
      regrowth of hair, and also as regards scalp sensitivity.

PMID- 11233734
TI  - [Soft tissue sarcomas of the hand: report of a radiation-induced case].
AB  - Soft tissue sarcoma surgery is based on techniques that are in the process of
      ongoing development. In this study, the case is reported of a female patient who
      was operated on at the age of 14 years for a primary synoviosarcoma of the
      dominant hand, which was treated by conservative surgery and 60 Gy adjuvant
      radiotherapy. Twenty-two years later, she presented with a clinical picture of
      recurrence, but with no detectable metastases. Amputation of the distal third of
      the forearm was performed. The anatomopathological examination showed the
      presence of a myxoid malignant fibrous histiocytoma. It was considered that this
      tumor had been radiation-induced. All the distinct diagnostic criteria were met,
      i.e., a latency of over two years, different diagnosis and the appearance of the
      tumor within (or next to) the irradiated field. Both the diagnostic methods (MRI,
      tumor biopsy, and CT scan of the chest to investigate possible tumor spread) and
      the surgical approach have been discussed. The latter has altered over the years
      from being systematically radical (amputation or compartimental resection) to
      systematically conservative (good local control via radiotherapy). The modern
      attitude reflects a return to a more balanced approach. The frequency of such
      tumors has probably been underestimated in reports in the literature, as the
      latency period can sometimes exceed 30 years, and an accurate determination of
      the etiology is not always possible. Two main factors should be taken into
      account in treatment strategy: i) distant metastases of high-grade soft tissue
      sarcomas often appear early in the course of the disease, and are not affected by
      surgery at the primary site; ii) local recurrence, which is associated with high
      morbidity, and is directly connected with incomplete resection. Technical
      progress and a multidisciplinary approach have resulted in more sophisticated
      treatment (allowing a larger surgical resection area, and better residual
      function). Surgical management remains the treatment of choice, as radiotherapy
      and chemotherapy have not demonstrated any positive effect on patient survival.

PMID- 11233735
TI  - [Use of the lateral tongue flap for closure of cleft palate. Retrospective study
      of seven cases].
AB  - Due to its central position, mobility and good blood supply, the tongue is a most
      suitable donor site for the closure of cleft palate fistulae. The aim of this
      retrospective study was to reassess the efficacy of the lateral tongue flap
      technique, first reported in 1884 and in use up to the 1970s, after which it was
      replaced by more sophisticated methods for the reconstruction of buccal and
      labial defects, which however could be deleterious to the patient. The results of
      the present study demonstrate the reliability and technical simplicity of the
      lateral tongue technique. The procedure took place in two stages, after which the
      patient was fed for five postoperative days by nasogastric tube, thereby
      facilitating the healing process via non-interference with scar tissue. Out of
      the seven patients who received treatment, six successful closures were noted,
      and only one partial failure was observed, in all cases without any functional
      sequelae involving the tongue.

PMID- 11233736
TI  - [Carboxymethylcellulose hydrogel-filled breast implants. Our experience in 15
      years].
AB  - The author reports 15 years of laboratory and surgical experience with the use of
      breast implants pre-filled with carboxy-methyl-cellulose gel which he has used
      since 1984. Laboratory tests and results are presented. The author has undertaken
      a retrospective analysis of 380 clinical cases since 1984. He concludes that
      there is a future role for breast implants containing a non-toxic, visco-elastic
      and biodegradable filling gel in conjunction with the manufacture of increasingly
      reliable implant linings.

PMID- 11233737
TI  - Progression curves for endometrial lesions.
AB  - OBJECTIVE: To derive a numeric measure for the progression of endometrial lesions
      as a baseline study for an eventual assessment of chemopreventive intervention
      efficacy. STUDY DESIGN: Tissue sections from normal endometrium at the
      proliferative and secretory phase, simple hyperplasia, atypical hyperplasia from
      cases free of concomitant adenocarcinoma and adenocarcinoma of the endometrium
      were recorded at high spatial resolution. Six cases from each diagnostic category
      were chosen as "typical," and 60 epithelial nuclei were randomly selected for
      measurement for each case. Discriminant analyses were carried out to derive a
      direction of progressive change in feature space and to correct the progression
      curve for the presence of cells not expressing progressive change among the
      random sample of nuclei. RESULTS: A well-conditioned progression curve was
      derived based on the mean discriminant function scores for each diagnostic
      category and the mean nuclear abnormality of the nuclei in each category, as
      expressed by their deviation in feature values from normal reference nuclei. The
      lesion signatures showed a clear trend toward extension into the range of higher
      nuclear abnormalities with increasing progression. There was an indication that
      abnormal endometrial lesions may comprise cases with distinctly different degrees
      of nuclear abnormality. CONCLUSION: A numeric assessment of lesion progression
      for endometrial lesions, based on karyometric measurements, is possible. The data
      suggest that additional analysis may provide further characterizing information
      for individual lesions.

PMID- 11233738
TI  - Microvessel density counting in breast cancer. Slides vs. digital images.
AB  - OBJECTIVE: To develop a program to assist the pathologist in the acquisition and
      evaluation of digital images to determine microvessel density (MVD) in tissues.
      STUDY DESIGN: Ten cases of breast cancer with a high degree of neovascularization
      were selected. A standard immunohistochemical method was used to highlight the
      microvessels (monoclonal anti-factor VIII, avidinbiotin-peroxidase complex
      method). Two pathologists (one senior [S] and one junior [J]) evaluated four
      areas of highest neovascularization ("hot spots") in the tumors. Microscopically
      MVD was determined in four chosen areas (400:1). From the center of each area two
      digital images were acquired at a magnification of 200:1. All counts made by
      microscopic observation were compared with those made on the digital images. To
      compare MVD counting at different resolution, two sets of images at different
      sampling densities (320 x 240 and 1,600 x 1,200) were assessed by the two
      pathologists. RESULTS: We obtained a good correlation (r = .98 for S and .96 for
      J) between the MVD counts obtained at the microscope (192.8 MV/mm2 [mean of S]
      and 181.8 MV/mm2 [mean of J]) and the MVD counts from digital images (153.2
      MV/mm2 [mean of S] and 171.0 MV/mm2 [mean of J]) at high resolution. The counts
      were lower for digital images at lower sampling density (125.0 MV/mm2 [mean of S]
      and 78.2 MV/mm2 [mean of J]). With low-resolution digital images only S
      maintained a good correlation (r = .96 for S and .34 for J) with the microscopic
      evaluation of MVD. Interobserver analysis showed a good correlation (r = .82 for
      the microscope and r = .78 for the digital images) of MVD evaluated either at the
      microscope or in high-resolution digital images. CONCLUSION: We demonstrated the
      functionality and usefulness of our program in performing MVD evaluation.
      Considering the capabilities of the program to store all images and microvessel
      marks and the reliability of MVD evaluation based on digital images, we consider
      this program the first step toward fully automated MVD assessment.

PMID- 11233739
TI  - Quantification of tumor cellularity and mitotic index in invasive ductal
      carcinoma of the breast.
AB  - OBJECTIVE: To evaluate the use of stereologically estimated tumor cell counts in
      the mitotic index as well as to investigate its correlation with the currently
      used method and test the reproducibility of the method. STUDY DESIGN: The
      stereologic method described by Simpson et al was used to estimate tumor
      cellularity in 50 invasive ductal carcinomas. Mitotic counts were also performed,
      and the mitotic index was calculated by the use of estimated tumor cell counts.
      Estimated cell counts and the mitotic index calculated were compared
      statistically with the actual cell counts and the traditional mitotic grades,
      respectively. Interobserver reproducibility of the method was also tested.
      RESULTS: Stereologically estimated tumor cell counts had a good correlation with
      actual cell counts (r = .891, P < .001). Besides, the mitotic indices calculated
      with tumor cell counts (calculated with both estimated and actual cell counts) in
      the denominator of the fraction of the mitotic index were in agreement with the
      currently used method (P < .01 for both). There was no statistically significant
      difference between the counts of two observers (P = .068). CONCLUSION: The
      suggested method, considering tumor cellularity as an influencing factor, was
      practical, reproducible and in agreement with the traditional method. This method
      should be studied in a large group of patients with follow-up data to determine
      the threshold values for different grades and determine its prognostic value
      during the disease course.

PMID- 11233740
TI  - Terminal uridine nick end labelling and mitosis in breast carcinoma. Correlation
      with tumor grade and p53 overexpression.
AB  - OBJECTIVE: To study the relationship of cell death and proliferation to
      histologic grade and p53 expression in invasive carcinoma of the breast. STUDY
      DESIGN: A total of 31 cases of infiltrating duct carcinoma of the breast were
      randomly selected. The terminal deoxynucleotidyl-transferase-mediated dUTP nick
      end labelling (TUNEL) reaction and p53 immunostaining were performed on
      representative paraffin-embedded tissue sections. Mitotic and apoptotic indices
      (MI and AI) were also measured on hematoxylin-eosin-stained sections. Histologic
      grade of infiltrating duct carcinoma was performed with the help of the
      Nottingham modification of the Bloom-Richardson system. Tumor grade and p53
      overexpression were correlated with MI, AI and AI detected by TUNEL. RESULTS:
      There were a total of 31 infiltrating duct carcinomas of the breast, of which 13
      cases were grade 1 and nine cases each were grade 2 and 3. Cells with positive
      TUNEL showed a strong brown nuclear positivity. TUNEL showed positivity from the
      periphery of the nuclear margin to the central portion. AI detected by TUNEL did
      not correlate with tumor grade (ANOVA, P > .05). MI was significant only in grade
      1 versus grade 3 and 2 versus grade 3 carcinomas (ANOVA, P < .01). The
      morphologic apoptotic index was significant only in grade 1 versus grade 3
      carcinomas. Nine cases showed p53 overexpression, and the rest of the cases were
      negative for p53 immunostaining. MI, AI and TUNEL were not significantly
      different in p53-negative and -positive groups. Pearson's correlation coefficient
      showed that AI and MI were significantly related, but there was no significant
      relation between AI detected by TUNEL and MI. CONCLUSION: MI is still more useful
      than AI or AI detected by TUNEL in differentiating various grades of carcinoma of
      the breast.

PMID- 11233741
TI  - Standardized AgNOR analysis as a prognostic parameter in endometrial carcinoma,
      endometrioid type.
AB  - OBJECTIVE: To evaluate interobserver reproducibility of histologic grade in
      endometrial adenocarcinomas of endometrioid type (EC), to assess the
      relationships between nuclear grade and the amount of argyrophilic nucleolar
      organizer region (AgNOR) proteins and to determine the prognostic value of AgNOR
      proteins and the main clinicopathologic parameters. STUDY DESIGN: Architectural
      and nuclear grading were independently assessed by two pathologists in 64
      formalin-fixed, paraffin-embedded surgical samples of EC obtained from an equal
      number of patients (age range, 38-84 years; mean, 63.5). Interobserver agreement
      was determined using the kappa statistic; discrepant cases were reviewed, and a
      consensus was reached. Standardized AgNOR analysis was performed according to the
      guidelines of the Committee on AgNOR Quantification, measuring the mean area of
      AgNORs per nucleus (NORA) by an image analysis system. RESULTS: The kappa values
      for interobserver agreement were substantial for architectural grading and
      moderate for nuclear grading. When NORA values were compared to the nuclear grade
      assessed by different observers, the most significant linear correlation (r =
      .713, P < .001) was found for the nuclear assessment obtained by consensus of the
      two pathologists. Moreover, statistical analysis allowed discrimination of
      architectural grade 1 from grade 2 and 3 EC. By the Kaplan-Meier method, the
      prognosis was worse for patients with higher NORA values (> 4.212 micron 2),
      while, by Cox multivariate analysis, AgNOR quantity emerged as an independent
      prognostic variable. CONCLUSION: Use of standardized AgNOR analysis may be an
      additional and objective tool in the assessment of histologic grade as well as a
      reliable method of determining prognosis in EC.

PMID- 11233742
TI  - Karyometry in Barrett's esophagus.
AB  - OBJECTIVE: To derive a progression curve for lesions in Barrett's esophagus based
      on karyometric features. STUDY DESIGN: High-resolution imagery of 900 nuclei from
      normal gastric tissue, Barrett's metaplasia, Barrett's high grade dysplasia and
      adenocarcinoma of the esophagus was recorded. Karyometric features were computed,
      and nuclear signatures and lesion signatures for these lesions were derived. A
      progression curve was defined. RESULTS: Esophageal lesions were distinctly
      different from the normal gastric fundus tissue, with nuclei from Barrett's
      metaplasia deviating from normal almost as much as nuclei from high grade
      dysplasia and adenocarcinoma. There was considerable case-to-case variability and
      overlap between lesions histologically assigned to different diagnostic
      categories. CONCLUSION: The karyometric data suggest that Barrett's metaplasia is
      a more developed lesion than previously assumed.

PMID- 11233743
TI  - Confocal analysis of phosphatidylserine externalization with the use of
      biotinylated annexin V revealed with streptavidin-FITC, -europium, -phycoerythrin
      or -Texas Red in oxysterol-treated apoptotic cells.
AB  - OBJECTIVE: To analyze externalization of phosphatidylserine via annexin V on
      apoptotic cells by laser scanning confocal microscopy and factor analysis of
      biomedical image sequences (FAMIS). STUDY DESIGN: Streptavidin-fluorescein
      isothiocyanate (FITC), -europium (Eu), -phycoerythrin (PE) and -Texas Red (TR)
      were chosen to reveal the binding of biotinylated annexin V on apoptotic U937
      human leukemic cells and ECV-304 human endothelial cells induced under treatment
      with 7-ketocholesterol or 7 beta-hydroxycholesterol. Excitation of each
      fluorochrome was obtained by selection of specific lines (351 + 364 nm, 488 nm)
      of the argon laser of a confocal microscope. Temporal and spectral series were
      performed to characterize each fluorochrome. FAMIS was applied to these series to
      estimate images corresponding to stains. RESULTS: Each fluorochrome was clearly
      distinguished, and images showed localization of phosphatidylserine, which was
      improved by image analysis. CONCLUSION: On apoptotic cells it is possible to
      analyze differences in the improved visualization of phosphatidylserine in series
      processed by FAMIS with the use of biotinylated annexin V revealed with
      streptavidin-FITC, -Eu, -PE or -TR.

PMID- 11233744
TI  - Prognostic significance of DNA ploidy determined by high-resolution flow
      cytometry in breast carcinoma.
AB  - OBJECTIVE: To assess the prognostic value of DNA ploidy in breast carcinoma and
      its relation to other established prognostic factors. STUDY DESIGN: We evaluated
      DNA ploidy in 303 breast carcinoma patients with a median follow-up of 63 months.
      Flow cytometry was performed on frozen tumor material, yielding histograms with
      narrow peaks (median coefficient of variation of 2.08). DNA ploidy pattern was
      classified as either diploid versus nondiploid, euploid (diploid and tetraploid)
      versus aneuploid or diploid/near-diploid (DNA index < 1.2) versus other, and
      correlated with relapse-free (RFS) and cancer-specific survival (CSS) along with
      tumor size, histologic grade and type, axillary lymph node involvement,
      menopausal and steroid receptor status, age and type of treatment. RESULTS:
      Seventy-one percent of tumors were DNA nondiploid (14% tetraploid and 57%
      aneuploid). There was a strong association between DNA ploidy and histologic
      grade. Histologic grade, lymph node status, tumor size and DNA ploidy (regardless
      of the classification used) were all significantly associated with RFS and CSS in
      multivariate analysis. CONCLUSION: These results suggest that DNA ploidy, at
      least when determined from frozen tumor tissue, is an independent prognostic
      factor in breast carcinoma; however, its prognostic power seems to be inferior to
      that of histologic grade, with which it strongly correlates.

PMID- 11233745
TI  - Molecular changes associated with prostate cancer development.
AB  - The epidemiologic characteristics of prostate cancer (PCa) have been recognized
      for several decades. It is of great importance to understand the factors
      responsible for prostate carcinogenesis, why some carcinomas remain "clinically
      silent" during life, whereas other tumors progress to present clinically and may
      lead to PCa-related death. A better understanding of these mechanisms in
      molecular genetic terms should point to more rational approaches to disease
      prevention, intervention and treatment. The aim of this review is to provide a
      comprehensive overview of the current state of knowledge regarding the molecular
      alterations of PCa.

PMID- 11233746
TI  - Tumor volume estimation by the percentage carcinoma method in uterine cervix
      carcinoma.
AB  - OBJECTIVE: To assess the capacity of the percentage carcinoma method to predict
      tumor volume in cervical carcinoma and generate a mathematical equation for
      calculation of tumor volume. STUDY DESIGN: Thirteen radical hysterectomy
      specimens were studied. The actual tumor volume was assessed by stereology. A
      factor was generated by the formula tumor volume = factor x percentage carcinoma
      x number of blocks. The percentage carcinoma was calculated by the grid method.
      Then tumor volume was estimated by the same formula. The relationship between
      actual and estimated tumor volumes was analyzed by Spearman's correlation.
      RESULTS: Correlation of the tumor volumes assessed by the two methods was
      excellent (r = .945) and statistically significant (P = .01). CONCLUSION:
      Percentage carcinoma assessed by the grid ratio method is highly predictive of
      tumor volume, but care must be taken not to overstate the importance of our
      results due to the small number of patients. The prediction of outcome in
      cervical carcinoma by means of percentage carcinoma should be evaluated in large
      clinical studies.

PMID- 11233747
TI  - Polymorphism of Ag(+)-NORs in cervical smears from women with cervical cancer.
AB  - OBJECTIVE: To evaluate Ag(+)-stained (Ag(+)-NOR) polymorphism in four groups of
      patients with various grades of cervical lesions and in a control group. STUDY
      DESIGN: Forty-five women were selected, diagnosed and classified on the bases of
      the Pap smear and colposcopy/biopsy at Hospital de Ginecologia y Obstetricia del
      Instituto Mexicano del Seguro Social in Monterrey, Mexico. Five categories were
      considered: (1) inflammatory, (2) low grade squamous intraepithelial lesions
      (LSILs), (3) high grade squamous intraepithelial lesions (HSILs), (4) invasive
      cervical cancer, and (5) normal. The cervical smears were stained by the Ag(+)
      NOR method. One hundred cells per slide were counted and classified according to
      the polymorphism of Ag(+)-NOR dots: typical (spherical) and atypical (large,
      kidney shaped and clustered). The four shapes of Ag(+)-NORs were quantified by
      percentage and transformed using the arcsine root procedure. RESULTS: Statistical
      analysis showed a significant decrease in spherical shape according to neoplastic
      development. The three atypical shapes showed a significant increase in patients
      with HSIL and invasive carcinoma in respect to LSIL. Principal components
      analysis grouped the data at five locations in the plane formed by the first two
      principal components according to the diagnosis. CONCLUSION: These findings
      suggest the potential diagnostic and prognostic value of the determination of
      Ag(+)-NOR polymorphism in cervical cytology studies.

PMID- 11233748
TI  - Animal studies of methylmercury and PCBs: what do they tell us about expected
      effects in humans?
AB  - Methylmercury and polychlorinated biphenyls (PCBs) exemplify the important
      interactions that should take place between epidemiological and laboratory
      investigations of developmental neurotoxicants. Often found in the same source,
      perhaps with multiplicative interactions, it is difficult to isolate specific
      profiles of effects without advanced behavioral procedures and controlled
      exposures using laboratory animals. The present review focuses on the effects of
      developmental exposure to methylmercury or PCBs as expressed in adult animals.
      The PCBs are subdivided into two structural classes, nonortho-substituted
      ("coplanar" or "dioxin-like") PCBs and ortho-substituted ("noncoplanar") PCBs, a
      distinction supported by different behavioral profiles and neural mechanisms of
      action. Methylmercury's profile is dominated by sensory effects with a likely
      cortical site of action. Some of these effects may be amplified with aging.
      Methylmercury's effects on functions generally termed cognitive can be understood
      by distinguishing between those reflecting the acquisition of a response
      consequence relationship from those reflecting memory or contextual influences
      over behavior. Methylmercury does not appear to impair memory or discriminations,
      but retards acquisition of a response-reinforcer relationship. Like
      methylmercury, non-ortho-substituted PCBs do not appear to degrade memory and
      contextual control. Ortho-substituted PCBs impair performance on certain
      spatially-based discrimination and memory tasks. Methylmercury and non-ortho
      substituted PCBs disturb the temporal pattern seen in fixed-interval schedules,
      but apparently without a significant change in the pattern of interresponse
      times. The ortho-substituted PCBs disrupted this pattern, but did so by
      increasing the number of short interresponse times.

PMID- 11233749
TI  - Prenatal exposure to PCBs and infant performance on the fagan test of infant
      intelligence.
AB  - A sample of infants was examined at conceptual age 67 weeks (6-month testing,
      N=230), and again at conceptual age 92 weeks (12-month testing, N=216) using the
      Fagan Test of Infant Intelligence (FTII). Analysis of the results revealed a dose
      dependent relationship between total umbilical cord-blood PCB levels and poorer
      FTII performance at both ages. A similar relationship was observed using a subset
      of the persistent and heavily chlorinated PCB congeners associated with Lake
      Ontario fish consumption (septa-, octa-, and nonachlorinated biphenyls) in
      children tested at 12-months but not at 6-months. These data replicate previous
      research (Jacobson et al., 1985) which demonstrated a dose-dependent relationship
      between prenatal PCB exposure and FTII performance in infants of Lake Michigan
      fisheaters. Analyses of FTII scores with cord-blood DDE and maternal hair
      methylmercury (MeHg) revealed no significant associations between FTII
      performance and either of these toxicants. The latter results replicate those of
      Myers et al., (1995) who found no effect of MeHg on FTII performance in
      Seychellois infants.

PMID- 11233750
TI  - Identification of functional domains affected by developmental exposure to
      methylmercury: Faroe islands and related studies.
AB  - The Faroe Islands study is a prospective study designed to assess the
      neurological and behavioral consequences of in utero exposure to methylmercury
      (meHg). Maternal exposure to meHg was through consumption of fish and
      intermittent higher-level exposure through pilot whale meat, while consumption of
      pilot whale blubber resulted in maternal exposure to PCBs. Analysis of the
      neurobehavioral domains affected revealed impairment in attention, memory, and
      auditory processing, impairment in primary auditory function, and to a lesser
      extent motor impairment. For four of the eight endpoints affected by meHg
      exposure atp < .10, impairment was also correlated (p < .10) with in utero PCB
      exposure as measured by cord tissue PCB levels. Further analyses provide evidence
      for an independent effect of PCBs and meHg on these endpoints. Cross-sectional
      studies in a smaller number of children in the Amazon and Madeira by the same
      group of investigators, in which average meHg maternal hair levels were about
      twice as high those in the Faroe Islands, identified auditory, visual, and/or
      motor deficits, with little or no evidence of deficits in attention or memory.
      However, the results of the cross-sectional studies must be interpreted with
      caution, due to limited statistical power as well as a lack of opportunity to
      correlate effects to in utero exposure.

PMID- 11233751
TI  - Effects of lead on gene expression.
AB  - Lead poisoning is a worldwide, environmental health-hazard that affects children
      and adults. In this review we discuss the effects of lead on gene expression due
      to both general and specific mechanisms. In particular we focus on the ability of
      lead to substitute for biologically essential metals such as calcium and zinc in
      metal-binding domains of cytoplasmic enzymes, nuclear transcription factors and
      other proteins. The binding of lead to these proteins causes an alteration of
      their activity resulting in aberrant expression of their own genes and in some
      cases their target genes. Finally, we discuss the impact of microarray technology
      on the study of the genome-wide effects of lead and other toxicants on gene
      expression.

PMID- 11233752
TI  - Glutamatergic components underlying lead-induced impairments in hippocampal
      synaptic plasticity.
AB  - Epidemiological investigations have established the relationship between chronic
      developmental lead (Pb) exposure and cognitive impairments in young children,
      defining Pb neurotoxicity as a significant pediatric health problem. Exposed
      animals have proven to be effective models of this condition, exhibiting similar
      sensitivity to the actions of Pb and replicating abnormal learning behaviors in
      exposed children. Research has extended these observations in animals to
      identifying the processes underlying the cognitive dysfunction, utilizing the
      long-term potentiation (LTP) paradigm as a correlate of learning ability. Results
      from these studies have been in widespread agreement in reporting impairments in
      synaptic plasticity. Exposure-related changes consist of increases in LTP
      induction threshold, decreases in magnitude of potentiation, and shortened LTP
      duration. Furthermore, while LTP may be more readily affected by Pb during early
      development, exposure initiated after weaning also potently affects synaptic
      plasticity. Biphasic dose-effect relationships also appear in which impaired LTP
      is observed at intermediate exposure levels (27-62 microg/100 ml), but not at
      higher exposures. Investigation of the synaptic processes underlying LTP has
      provided additional insight into the bases of the impaired potentiation and
      diminished cognitive ability. Biochemical and neurophysiological approaches have
      found stimulated glutamate release to be diminished in hippocampus at blood Pb
      values where deficits in LTP have been observed. Multiple actions of Pb may be
      involved at this exposure level since animals exposed postweaning exhibited
      similar decrements in evoked glutamate release to those exposed continuously from
      conception, similar to the observations in measures of LTP. A biphasic dose
      effect relationship was also found in which stimulated glutamate release in
      hippocampus was decreased at intermediate exposures, but not at higher levels. A
      direct inhibitory effect of Pb2+ on NMDA receptor function does not appear to
      occur at environmentally relevant exposure levels, but both exposure-induced
      increases and decreases in receptor density have been reported by different
      workers. Evidence from behavioral and neurophysiological investigations can be
      explained by increased NMDA receptor density on the bases of increased
      sensitivity to agonists and decreased sensitivity to antagonists. From this body
      of findings it is apparent that decreases in stimulated glutamate release are a
      significant contributing factor to the exposure-related changes seen in LTP.
      Furthermore, despite general agreement on the actions of Pb on synaptic
      plasticity, reports of exposure effects on NMDA receptor function have been
      relatively variable, suggesting either that the nature of the receptor changes
      are dependent on exposure conditions or that the receptors are secondarily
      affected by Pb actions produced at signal transduction or cellular loci.

PMID- 11233753
TI  - Disruption of the zinc finger domain: a common target that underlies many of the
      effects of lead.
AB  - The health risks associated with exposure to heavy metals such as lead (Pb)
      remain a major public health concern. The zinc finger is a major structural motif
      involved in protein-nucleic acid interactions and is present in the largest
      superfamily of transcription factors. Zinc (Zn) ions coordinate this finger-like
      structure through bonds created with cysteine and histidine residues. Little
      information exists on the effects of heavy metals on proteins that contain
      structural repeats of this kind. Studies by us in the nervous system have shown
      that factors containing such motifs could be potential targets for perturbation
      by Pb. We have observed that metals such as Pb interfered with the DNA-binding
      properties of Sp1 and Egr-1, both in vivo and in vitro. Pb could also directly
      interfere with the DNA-binding of a recombinant human Sp1 protein. More recently,
      the effects of Pb on the DNA-binding of the zinc finger protein transcription
      factor IIIA (TFIIIA) have been demonstrated. Analysis on the effects of Pb on Sp1
      revealed that alterations in its DNA-binding were commensurate with changes in
      the expression of its target genes. The action of Pb on Sp1, Egr-1, and TFIIIA
      suggests that it can also target other cellular proteins that contain the zinc
      finger motif and reveals this protein domain as a potential mediator for Pb
      induced alterations in protein function. Thus by specifically targeting zinc
      finger proteins (ZFP), Pb is able to produce multiple responses through its
      action on a common site that is present in enzymes, channels and receptors.

PMID- 11233754
TI  - Lead enhances NGF-induced neurite outgrowth in PC12 cells by potentiating
      ERK/MAPK activation.
AB  - Although the neurotoxicity of lead exposure is well documented, the cellular and
      molecular mechanisms underlying lead neurotoxicity have not been well defined. We
      have investigated the effect of lead on nerve growth factor (NGF)-induced neurite
      outgrowth in PC12 cells and the role in this process of extracellular signal
      regulated protein kinase (ERK), a key component of NGF-induced differentiation.
      We found that exposure of cells to lead acetate (0.1-100 microM) resulted in
      enhanced NGF-induced neurite outgrowth. Lead exposure also promoted formation of
      multiple neurites per cell in NGF-treated cells. However, lead alone did not
      cause neurite outgrowth. Lead also enhanced NGF-induced ERK phosphorylation and
      activation, but lead alone did not stimulate ERK. The MAP kinase kinase (MEK)
      inhibitor, PD98059, significantly decreased the effect of lead on NGF-induced
      neurite outgrowth and ERK activation. These findings indicate that exposure of
      cells to low, toxic levels of lead amplifies growth factor-induced neurite
      outgrowth by means of an ERK-dependent signaling pathway.

PMID- 11233755
TI  - Association of silicofluoride treated water with elevated blood lead.
AB  - Previous epidemiological studies have associated silicofluoride-treated community
      water with enhanced child blood lead parameters. Chronic, low-level dosage of
      silicofluoride (SiF) has never been adequately tested for health effects in
      humans. We report here on a statistical study of 151,225 venous blood lead (VBL)
      tests taken from children ages 0-6 inclusive, living in 105 communities of
      populations from 15,000 to 75,000. The tests are part of a sample collected by
      the New York State Department of Children's Health, mostly from 1994-1998.
      Community fluoridation status was determined from the CDC 1992 Fluoridation
      Census. Covariates were assigned to each community using the 1990 U.S. Census.
      Blood lead measures were divided into groups based on race and age. Logistic
      regressions were carried out for each race/age group, as well as above and below
      the median of 7 covariates to test the relationship between known risk factors
      for lead uptake, exposure to SiF-treated water, and VBL >10 microg/dL. RESULTS:
      For every age/race group, there was a consistently significant association of SiF
      treated community water and elevated blood lead. Logistic regressions above and
      below the median value of seven covariates show an effect of silicofluoride on
      blood lead independent of those covariates. The highest likelihood of children
      having VBL> 10 microg/dL occurs when they are both exposed to SiF treated water
      and likely to be subject to another risk factor known to be associated with high
      blood lead (e.g., old housing). Results are consistent with prior analyses of
      surveys of children's blood lead in Massachusetts and NHANES III. These data
      contradict the null hypothesis that there is no difference between the toxic
      effects of SiF and sodium fluoride, pointing to the need for chemical studies and
      comprehensive animal testing of water treated with commercial grade
      silicofluorides.

PMID- 11233756
TI  - Neuron-astrocyte interactions: implications for cellular energetics and
      antioxidant levels.
AB  - The interaction between astrocytes and neurons is examined from the standpoint of
      glutamate and glutathione (GSH) metabolism. These examples are outlined to
      provoke a reformulation of concepts of the inter-dependence between these 2 cell
      types, not only in terminating excitotoxicity, but also in assuring proper
      energetics and neuromodulation by astrocytic removal of glutamate via the
      astrocyte-specific glutamate transporters, GLT1 and GLAST. In addition, the role
      of astrocytes in the synthesis of neuronal GSH is detailed. The neuron-astrocyte
      interaction permits widely divergent aspects of brain energetics and modulation,
      and undoubtedly brain pathology where the functional unit is altered. Testing the
      developmental effects of compounds on this interaction is warranted and likely to
      establish the mechanisms by which it is compromised in a variety of disease
      states.

PMID- 11233757
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin alters hippocampal astroglia-neuronal gap
      junctional communication.
AB  - Halogenated aromatic hydrocarbons (HAHs) such as dibenzo-p-dioxins are known to
      alter cognitive function. However, the cellular basis of this disruption is not
      well understood. One possible deleterious effect of exposure to HAHs could be on
      gap junctional intercellular communication (GJIC) between neurons and astroglia
      in the brain. As such, this study examined the effects of the highly toxic
      prototypic HAH, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on GJIC in rat
      hippocampal primary cell culture. Initial measurements of fluorescence recovery
      after photobleaching (gap-FRAP) showed dye transfer between astroglia and
      neurons. N-octanol, a lipophilic alcohol known to uncouple cells by decreasing
      the open probability of gap junctional channels blocked astroglial-neuronal (A-N)
      communication as well as astroglial-astroglial (A-A) communication. TCDD
      initially downregulated GJIC between neurons and astroglia of treatment, but had
      no effect on astroglial cell pairs. These results indicate the presence of GJIC
      between neurons and astroglia in culture and demonstrate different sensitivities
      of gap junction responses to TCDD in homologous and heterologous cell pairs. The
      finding that 2,3,7,8-TCDD disrupts GJIC through A-N but not A-A channels may have
      important implications for impaired brain function resulting from developmental
      exposure to TCDD.

PMID- 11233758
TI  - Muscarinic receptors, protein kinase C isozymes and proliferation of astroglial
      cells: effects of ethanol.
AB  - Activation of cholinergic muscarinic receptors (primarily the M3 subtype) causes
      proliferation of astroglial cells and this effect is inhibited by low
      concentrations (10-50 mM) of ethanol. Investigations on the signal transduction
      pathways activated by muscarinic receptors in a human astrocytoma cell line
      (1321N1) have focused on protein kinases C (PKC). Among PKC isozymes expressed in
      this cell line (alpha, epsilon, zeta), the atypical PKCzeta appears to play a
      primary role in the mitogenic action of muscarinic agonists. We investigated
      whether activation of these PKC isozymes may be affected by ethanol at
      concentrations that can inhibit muscarinic receptor-induced proliferation.
      Carbachol caused an increase in phorbol ester binding and translocation of
      PKCepsilon, however, these were inhibited only by 100-200 mM ethanol. On the
      other hand, translocation of the atypical PKCzeta to the perinuclear area by
      carbachol was inhibited by ethanol in a dose-dependent manner (10-100 mM). These
      results suggest that activation of PKCzeta may represent a relevant target for
      the inhibitory effect of ethanol on muscarinic receptor-induced glial cell
      proliferation.

PMID- 11233760
TI  - Sensitivity of immature neurons in culture to metal-induced changes in reactive
      oxygen species and intracellular free calcium.
AB  - It is widely recognized that prolonged increases in reactive oxygen species (ROS)
      and intracellular free calcium ([Ca2+]i) are part of a signaling pathway leading
      to cell death. ROS production resulting in oxidative stress and disruption of
      calcium homeostasis leading to increases in [Ca2+]i have been described as early
      events following exposure to a number of neurotoxicants. In order to determine
      the intrinsic sensitivity of developing neurons to toxicant-induced oxidative
      stress and disruption of calcium homeostasis, we exposed immature neurons to iron
      (Fe2+) or methylmercury (MeHg). Primary cultures of cortical cells (prepared from
      1 day old rats) or cerebellar granule cells (prepared from 7 day old rats) were
      exposed to the toxicants on day in vitro (DIV) 1 (immature response to receptor
      agonists) or DIV 7 (mature response to receptor agonists). ROS was measured using
      the fluorescent probe 2',7'-dichlorodihydrofluorescin. In both cerebellar granule
      cells and cortical cells, Fe2+ or MeHg exposure (0.1-30 microM) produced time-
      and concentration-dependent increases in ROS. In general, the increase in ROS
      induced by both metals was greater in immature cells compared to mature cells,
      except for cerebellar granule cells in which the effects of Fe2+ were similar at
      DIV1 and 7. Changes in intracellular cation concentrations (including Ca2+) were
      measured using the fluorescent probe fluo-3. MeHg exposure produced a time- and
      concentration-dependent increase in fluo-3 fluorescence in both cerebellar
      granule cells and cortical cells. In cortical cultures, the fluorescence increase
      after MeHg exposure was greater in immature cells. In contrast, mature and
      immature cells were equally sensitive to the effects of MeHg in cerebellar
      granule cell cultures. These results suggest that there may be inherent
      differences in the sensitivity of neurons to toxicant-induced increases in ROS
      and [Ca2+] depending upon age and cell type.

PMID- 11233759
TI  - Polychlorinated biphenyls and methylmercury alter intracellular calcium
      concentrations in rat cerebellar granule cells.
AB  - Assessments of the effects of exposure of human populations to complex
      environmental contaminants, such as those found in contaminated fish, necessitate
      the investigation of contaminant interactions. We have recently demonstrated that
      polychlorinated biphenyls (PCBs) and methylmercury (MeHg) synergistically reduce
      rat brain striatal slice dopamine (DA) and increase media DA concentrations in
      vitro. To better understand the mechanism(s) by which these effects occur we
      examined the effects of these two contaminants, either alone or in combination,
      on intracellular calcium concentrations ([Ca2+]) in rat cerebellar granule cells
      using flow cytometry. Exposure of granule cells to either 2,2'-dichlorobiphenyl
      (2,2'-DCB) or MeHg dose-dependently increased [Ca2+]i. Granule cells exposed to
      1.5 microM MeHg and 2.5 or 5.0 microM 2,2'-DCB showed synergistic increases in
      [Ca2+]i which were greatest at exposure times of 5 and 10 min. Higher dose
      combinations, including 2.0 microM MeHg and 10 or 20 microM 2,2'-DCB, or longer
      duration of exposure to lower concentrations of contaminant mixtures, reduced
      [Ca2+]i in the granule cells compared to elevations seen following exposure to
      MeHg only, suggesting a dose-dependent antagonism between PCBs and MeHg. These
      data provide evidence for the synergistic and antagonistic interactions of PCBs
      and MeHg at the level of [Ca2+]i regulation that may ultimately lead to
      alterations in cellular function, including changes in dopamine regulation.

PMID- 11233761
TI  - Effects of single injection of methylazoxymethanol at postnatal day one on cell
      proliferation in different brain regions of male rats.
AB  - Methylazoxymethanol (MAM), an aglycone of cycasin extracted from Cycad seed, is
      reported to induce microencephaly in rats after prenatal or postnatal
      administration. Forty postnatal day (PND) 1 rats derived from 8 timed-pregnant
      rats were used to evaluate the effect of a single subcutaneous injection of MAM
      on PND 1 on cell proliferation in rat brain. All dams were fed NIH-31 diet. In
      the MAM-treated group, each pup received a single injection of MAM at 10 mg/kg
      body weight. In the control group, pups were injected with saline solution. Body
      weight of pups was recorded on PNDs 1, 7, 14, 21, 28, and 60. One male pup in
      each litter was removed for sacrifice by decapitation on PNDs 7, 14, 21, 28, and
      60. The brain was removed and dissected to obtain the brain stem, caudate
      nucleus, cerebellum, frontal cortex, hippocampus, hypothalamus, and olfactory
      bulb. The percentage (%) of S-phase cells in the cell cycle for each region was
      measured as index of cell proliferation. A significant (p<0. 05) reduction in
      body weight was detected on PND 7. The % S-phase cells in cerebellum on PND 7 and
      olfactory bulb on PND 14 initially increased and then later decreased. There were
      significant decreases in the % S-phase cells in both cerebellum and caudate
      nucleus on PND 21 and olfactory bulb on PND 28. No significant changes were found
      in other brain regions in cell proliferation activity between the control and MAM
      treated groups. The % of S-phase cells in cerebellum decreased 65% on PND 60 but
      lacked statistical significance due to small number of animals used in each
      group. The results indicated that a single injection of MAM at 10 mg/kg/body
      weight on PND 1 inhibited cell proliferation in the cerebellum in a manner that
      could lead to microencephaly.

PMID- 11233762
TI  - The special and unique vulnerability of children to environmental hazards.
AB  - There are several factors that alter an individual's risk for an environmentally
      related illness. A major determinant is the developmental stage of the
      individual. The environment can be divided into three spheres: physical,
      biological and social. The components of each sphere are dependent on
      developmental stage. This presentation will discuss the components of each of
      these spheres and their variability with age. The discussion will be illustrated
      with known examples of environmentally related disease.

PMID- 11233763
TI  - Thyroid hormone action in fetal brain development and potential for disruption by
      environmental chemicals.
AB  - Thyroid hormone is well-known to play essential roles in brain development.
      Therefore, environmental factors that interfere with thyroid function or thyroid
      hormone action may produce deleterious effects on brain development by
      interfering with thyroid hormone action in the developing brain. The purpose of
      this review is to identify in broad terms the gaps in our knowledge of thyroid
      hormone action in brain development, to relate these gaps to present information
      on thyroid disruption, and to review briefly our recent research that is germane
      to these issues. The endocrinology of the thyroid system is first reviewed
      briefly with an emphasis on the neuroendocrine and extrathyroidal mechanisms
      controlling circulating levels of thyroid hormones. The second section reviews
      the evidence that thyroid hormone is important for fetal, as well as neonatal,
      brain development. We review the mechanism of thyroid hormone action in the third
      section and briefly relate this information to information about the mechanism of
      thyroid hormone action on brain development. In the final section, we review the
      endocrinology of thyroid disruption with an emphasis on disruption of thyroid
      hormone action.

PMID- 11233764
TI  - Developmental neurotoxicity of endocrine disrupters: focus on estrogens.
AB  - A number of different environmental compounds are proposed to interact with the
      endocrine system (i.e., endocrine disrupters). Many of these have estrogenic
      effects in vitro and/or in vivo. Recent reviews have focused attention on the
      need for assessing the neurotoxicity of these compounds following developmental
      exposure. This attention comes in part from the literature on the effects of
      developmental exposure to exogenous estrogen on later behavioral and
      neuropathological alterations. A review of the ongoing neurobehavioral and
      neuropathological studies at the National Center for Toxicological Research on
      four such estrogen mimics (genistein, methoxychlor, nonylphenol, and ethinyl
      estradiol) is presented with results indicating that intake of a sodium solution
      is sensitive to these estrogen mimics. Developmental dietary exposure in male and
      female rats resulted in increased consumption of the sodium solution. Volume of
      the sexually dimorphic nucleus of the medial preoptic area was reduced by
      genistein, nonylphenol, and ethinyl estradiol exposure in males. The regulatory
      impact of these data and the directions for future research are discussed.

PMID- 11233765
TI  - Evaluation of techniques for assessing neurobehavioral development in children.
AB  - A battery of tests has been designed to explore functional disabilities in
      children 10-12 years of age arising from adverse conditions during early
      development. At these ages, it becomes possible to use more complex and
      challenging tests than those typically used at earlier ages. Although the battery
      was prompted originally by questions arising from methylmercury exposure, it was
      also designed for applicability to neurotoxicant exposures arising from
      pesticides, solvents, persistent organic pollutants such as PCBs and dioxins,
      other metals, and nutrient excesses and deficiencies as well. The test battery
      includes the following categories: (1) neuropsychological tests with established
      psychometric properties not widely exploited in studies of developmental
      neurotoxicity; (2) electrophysiological and behavioral tests of sensory
      functioning spanning a broader range of indices than those used generally in
      studies of neuropsychological development; and (3) adaptations of performance
      tasks used previously only in animals. The battery was developed in Rochester,
      New York, and then field-tested on a group of 61 children in the Republic of the
      Seychelles, where the Ministry of Health had established the Child Development
      Center. Our findings suggest a number of tests and procedures with the potential
      for inclusion in test batteries aimed at the exploration of adverse
      neurodevelopmental effects.

PMID- 11233766
TI  - Smiling faces and other rewards: using the Behavioral Assessment and Research
      System (BARS) with unique populations.
AB  - Concern about the exposure of children and adolescents to occupational and
      environmental hazards has increased, and so has the need to develop testing
      methods that can adequately assess the effects of exposure in children. A
      computerized testing system, the Behavioral Assessment and Research System
      (BARS), was successfully modified to test both younger populations and
      populations which do not speak English, the original language of the battery.
      These adaptations were modifications of the existing features of the BARS system
      which was designed to assess the broadest possible audience: simple language
      instructions broken down into basic concepts (step-by-step training with
      competency testing at each instruction step); a token dispenser along with a
      "smiling face" stimulus that reinforced appropriate performance; and adjustable
      parameter settings (e.g., number of trials, difficulty). Data from four groups
      demonstrate the feasibility of using BARS with children as young as preschool age
      and for non-English speaking children.

PMID- 11233767
TI  - Neurodevelopmental effects: making the case for biologic plausibility.
AB  - It has been suggested that the most critical missing link between science and
      policy is causality; that is, the establishment of a definite cause-effect
      relationship between exposure and adverse health effects. As has been clearly
      demonstrated by the decades-long tobacco debate, causality is extremely difficult
      to establish with absolute certainty, particularly in the minds of scientists.
      Because of this, it has been suggested that a "weight of evidence" approach based
      on biologic plausibility should be used as a surrogate for causality when
      translating science into policy and public health practice. In the case of
      neurodevelopmental effects, the case for biologic plausibility is supported by
      scientific findings from three broad areas consisting of wildlife biology,
      toxicology, and epidemiology. A striking example of this is provided by research
      findings from the Great Lakes Basin, an area which has been the focus of
      significant scientific research for the last thirty years in these three broad
      areas. In this paper, we examine relevant findings from the Great Lakes Basin and
      elsewhere as they relate to establishing and supporting the biologic plausibility
      of neurodevelopmental effects associated with environmental exposures to
      persistent toxic substances.

PMID- 11233768
TI  - The functional observational battery in adult and developing rats.
AB  - Neurobehavioral screening methods, such as the functional observational battery
      (FOB), are now widely used to identify potential neurotoxicity of new and
      existing chemicals. These methods have been validated and a large database now
      exists for the effects of a wide range of chemicals. Since most of the
      observations recorded are subjective, the quality of the test data depends
      largely on the observer's ability to detect and describe changes in the animal's
      behavior and neurologic function. Efforts are underway to aid in the training of
      observers and to achieve consistency across laboratories in the use of these
      methods. With the increasing concern over potential neurotoxicological
      consequences of chemical exposure in the developing organism, there is growing
      interest in testing laboratory animals at very young ages. We present here an
      initial report of the development of an FOB suitable for young rats, using some
      modifications of the individual adult FOB test measures to make them age
      appropriate. We have evaluated pre- and postweanling rats to determine the range
      of behaviors (as evaluated with the FOB) displayed at each age, develop
      appropriate scoring criteria, and collect control data to document the ontogeny
      of each of the endpoints in the FOB. This revised FOB protocol may be useful for
      assessing behavioral or neurological changes due to acute chemical exposure in
      young rats, or following gestational/lactational exposures typical of
      developmental neurotoxicity studies.

PMID- 11233769
TI  - Multigenerational exposure to dietary genistein has no severe effects on nursing
      behavior in rats.
AB  - The phytoestrogen and principal isoflavone in soy, genistein, has adverse effects
      on reproductive physiology in rodents. Since physiology and behavior are both
      sensitive to perturbations by estrogens, genistein may produce behavioral
      alterations as well. This paper reports one aspect of a study in which several
      adult rodent behaviors will be assessed following long term multigenerational
      dietary exposure to genistein. Since maternal care may affect offspring behaviors
      in adulthood, it is important to determine the potential for genistein to affect
      maternal behavior. Here, rats (F0 generation) were fed soy-free diets containing
      0, 5, 100, or 500 ppm genistein (approx. 0, 0.4, 8, and 40 mg/kg/day for an
      adult) beginning on postnatal day (PND) 42. Two generations of offspring (F1 and
      F2) were continued on these diets and all treatment groups of the F3 generation
      were returned to 0 ppm at weaning (PND 22). In the first 3 weeks after
      parturition (for each generation), dams were assessed on 6 occasions for the
      presence of the arched back posture with at least one pup nursing. Data were
      analyzed by 3 way repeated measures analysis of variance (ANOVA) with generation,
      treatment, and postnatal day as factors, and p<0.05 required for significance.
      There were no significant interactions among treatment, generation, or day, and
      no overall effects of treatment or generation. As expected, there was a
      significant overall effect of day, with animals nursing less on later days
      (p<0.0001). As assessed here, these results suggest that lifelong and
      multigenerational exposure to dietary genistein has no severe effects on nursing
      behavior in rodents.

PMID- 11233771
TI  - The challenge of p53 as prognostic and predictive factor in Hodgkin's or non
      Hodgkin's lymphoma.
AB  - The results of individual studies examining the role of p53 as a predictive and
      prognostic factor in lymphoid malignancies have varied considerably. In order to
      summarize the available data on the overexpression or mutation of p53 in
      Hodgkin's and non-Hodgkin's lymphoma, a systematic literature review was
      performed. Twenty-four studies met the eligibility criteria. With respect to non
      Hodgkin's lymphoma, most studies seem to support the hypothesis that patients
      whose tumors contain wild-type p53 respond better to treatment and have increased
      survival rates. If true, the implication may be that patients with p53 mutated
      tumors could be selected for non-standard treatment. With respect to Hodgkin's
      lymphoma, comparable associations were rarely reported. However, techniques for
      assessing the inactivation of p53 varied widely. Furthermore, in most instances,
      the study design and/or statistical methods did not allow sufficient analyses of
      the influence of confounding factors such as histologic type, stage, first-line
      and salvage treatment, etc. Therefore, it remains unclear whether the apparent
      influence of p53 status on outcome in non-Hodgkin's lymphoma is independent of
      established parameters such as stage, performance status, etc. Further studies
      involving large numbers of specimens derived from patients treated in clinical
      trials with identical regimens, follow-up and salvage strategies are needed.
      These studies should also be stratified according to histologic subtypes.

PMID- 11233770
TI  - Establishment of serum-free pre-colony forming unit assays for differentiation of
      primitive hematopoietic progenitors: serum induces early macrophage
      differentiation and inhibits early erythroid differentiation of CD34++CD38-
      cells.
AB  - In this report we show that serum has differentiation-inducing effects on
      primitive hematopoietic progenitor cells with the CD34++CD38- immunophenotype.
      Using the pre-colony forming unit (pre-CFU) assay as a model for early
      myelopoiesis, we compared the effects of serum-containing and serum-free media
      and evaluated different cytokine cocktails [interleukin (IL)-1, IL-3, IL-6, kit
      ligand with and without the Flt3/Flk2 ligand (FL)]. In this assay, pre-CFUs are
      defined as cells unable to form colonies when plated directly in semi-solid
      assays, but which can differentiate into CFUs when cultured in liquid medium
      containing early-acting cytokines. In one of the investigated serum-free media,
      the average myeloid expansion in liquid medium reached up to more than 50% of
      that obtained in serum-containing medium. In addition, our experiments revealed
      differences in the clonogenic output between cells cultured in serum-free medium
      and those cultured in serum-containing medium, demonstrating that serum has a
      monocyte differentiation-inducing effect on primitive hematopoietic progenitors.
      Also in serum-free medium, higher proportions of erythroid progenitors were
      generated. These differentiation-inducing effects of serum further emphasize the
      need for serum-free culture protocols for hematopoietic graft engineering.
      Addition of FL to the culture media ameliorated cellular expansion and resulted
      in a decrease in the proportion of erythroid and granulocyte progenitors and an
      increase in the proportion of monocyte progenitors. In conclusion, this study
      shows that good serum-free conditions are available for differentiation assays
      with primitive hematopoietic progenitors and demonstrates that serum and FL have
      biasing effects on the initial phase of hematopoietic differentiation, favoring
      the monocyte lineage.

PMID- 11233772
TI  - Change in erythropoiesis with gestational age during pregnancy.
AB  - To investigate the changes in erythropoiesis during pregnancy, 342 pregnant and
      postpartum women were examined for reticulocyte subpopulations, reticulocyte
      maturity index (RMI), and serum transferrin receptor (sTfR) levels. The
      reticulocyte subpopulations were analyzed by flow cytometry, and the sTfR
      concentration was measured by an immunoenzymometric method. There were no
      significant differences in the values of reticulocyte subpopulations, RMI, and
      sTfR between first trimester and non-pregnant women. However, the RMI and sTfR
      concentration increased gradually from the second trimester of pregnancy, during
      which time values were twofold higher than those in the first trimester, and
      peaked in the third trimester. Then the RMI and sTfR values decreased abruptly 1
      4 weeks postpartum and finally dropped to the levels of non-pregnant women 5
      weeks after delivery. The maternal sTfR concentration correlated significantly
      with the corrected reticulocyte count (r = 0.52, P < 0.01), RMI (r = 0.67, P <
      0.01), and high fluorescence reticulocytes (HFR) (r = 0.62, P < 0.01); however,
      the serum ferritin level correlated poorly with the reticulocyte subpopulations
      during pregnancy. In conclusion, erythropoiesis increases with gestational age
      during pregnancy and returns to normal 5 weeks after delivery. Measurement of
      sTfR in combination with RMI may improve the assessment of erythropoietic
      activity during pregnancy.

PMID- 11233773
TI  - Oxidative damage of erythrocytes: a possible mechanism for premature hemolysis in
      experimental visceral leishmaniasis in hamsters.
AB  - Visceral leishmaniasis is accompanied by severe anemia and pancytopenia. Reactive
      oxygen species are known to contribute to the pathogenesis of several red blood
      cell (RBCs) disorders. The present study reveals the extent of oxidative stress
      and the efficacy of the primary antioxidant system in erythrocytes of hamsters in
      the progressive anemic response at different stages of leishmanial infection.
      Increased intracellular precipitation of Heinz bodies secondary to oxidative
      denaturation of hemoglobin and enhanced formation of malonyldialdehyde suggest
      oxidative damage of erythrocytes, both in the hemoglobin and cell membrane,
      respectively. Decreased activities of superoxide dismutase and catalase in the
      infected animals indicate the generation of O2*- and H2O2, which in turn may
      produce the highly reactive *OH species. Decreases in the reduced glutathione
      level along with the decreased activities of glutathione reductase and
      glutathione peroxidase point to a deficient antioxidant defense system during the
      post-infection period. Accentuated degradation of both cytoskeletal and integral
      membrane proteins after 3 months of infection may eventually lead to membrane
      destabilization and early lysis of erythrocytes in experimental visceral
      leishmaniasis.

PMID- 11233774
TI  - Massive hemothorax due to intrathoracic extramedullary hematopoiesis in a patient
      with hereditary spherocytosis.
AB  - Extramedullary hematopoiesis (EMH) is a rare disorder, characterized by the
      appearance of hematopoietic elements outside of the bone marrow, which occurs in
      patients with chronic myeloproliferative disorders or congenital hemolytic
      anemias. We report on a 64-year-old man with hereditary spherocytosis, who
      presented with anemia, jaundice, intrathoracic EMH, and massive hemothorax. The
      diagnosis of EMH was established after computer tomography (CT)-guided
      punctuation of the paravertebral mass. The patient underwent splenectomy and
      thoracic drainage. After 1 year, the patient is in good health, with normal
      hemoglobin values, and hemothorax has not recurred.

PMID- 11233775
TI  - 6-Phosphogluconate dehydrogenase deficiency in an Italian family.
AB  - A rare case of hereditary erythrocyte enzymopathy, namely 6-phosphogluconate
      dehydrogenase (6PGD) deficiency, was found in an Italian family. The activity of
      the enzyme was reduced to 35% in the propositus and her mother, but was normal in
      the other three members of the family. The 6PGD deficiency was associated with a
      variable reticulocyte count and recurrent increased unconjugated bilirubinemia
      without anemia in the propositus, while no clinical or hematological symptoms
      were evident in her mother. Increased levels of erythrocyte pyruvate kinase (PK)
      activity and reduced glutathione (GSH) were observed, indicating a slight
      decrease in mean red blood cell (RBC) age and an activation of reducing systems.
      The episodic hemolytic events with jaundice observed in the propositus may be the
      result of a defective RBC ability to counteract conditions of marked oxidative
      stress. In this report the importance of 6PGD estimation for a proper analysis of
      glucose-6-phosphate dehydrogenase (G6PD) deficiency is also highlighted. In fact
      in the present study, the presence of 6PGD deficiency could be mistaken for a
      partial G6PD deficiency if the assay of G6PD activity was performed without
      correcting for 6PGD activity.

PMID- 11233776
TI  - Littoral cell angioma as a rare cause of splenomegaly.
AB  - A 58-year-old, otherwise healthy man presented with a sudden onset of watery
      diarrhea. A pseudomembranous colitis due to antibiotics was identified as the
      cause of the diarrhea. Enlargement of the spleen was detected during the
      evaluation. The enlarged, plump spleen (20 cm long, 7.1 cm wide) had multiple
      nodules that differed in size from 1 to 8 cm. Neither clinical nor other symptoms
      of an underlying malignant disease could be detected. Because the signs were of
      little diagnostic value we arranged a splenectomy, which showed a littoral cell
      angioma (LCA) to be the cause of splenomegaly. In addition to the case report, we
      have reviewed the literature, clinical manifestations, differential diagnosis,
      special gross and microscopic pathological findings, and the location of this
      benign vessel tumor in the pathology of the spleen.

PMID- 11233777
TI  - Interferon-alpha activity in a case of severe autoimmune lymphoproliferative
      disease.
AB  - Autoimmune lymphoproliferative disease (ALD) is a rare familial disorder.
      Clinical and laboratory features of this disease include a generalized
      lymphadenopathy, splenomegaly, increased levels of circulating CD3+ with low
      levels of CD4+, CD8+ T-cells, and autoimmune phenomena, characteristics that the
      autoimmune lymphoproliferative syndrome (ALPS) have in common. Treatment usually
      consists of different supportive therapies. We report on the case of a young man
      affected by ALD who became resistant to steroids and was unresponsive to
      cyclosporine. Nevertheless, he was successfully treated with interferon (IFN)
      alpha, resulting in a long-lasting, clinically complete remission.

PMID- 11233778
TI  - Effects of amifostine in a patient with an advanced-stage myelodysplastic
      syndrome.
AB  - We report on a 63-year-old man with myelodysplastic syndrome at the stage of a
      refractory anemia with an excess of blasts in transformation (MDS-RAEB-T), first
      diagnosed in December 1996. After a period of stability, with no need for
      transfusions, the MDS progressed into acute myeloid leukemia (AML) in August 1998
      with the emergence of a cytogenetic abnormality (11q-). Two courses of
      chemotherapy were given, resulting in prolonged pancytopenia; however, no
      clearance of bone marrow (BM) blasts was achieved. At that time, severe
      infections and daily epistaxis occurred. Frequent transfusions of packed red
      blood cells (RBC) and platelets (2-3/week) were necessary. After 2 months of
      persisting severe pancytopenia, we started a therapy with amifostine: 4 x 250 mg
      intravenously (i.v.) weekly for 1 month, followed by a maintenance therapy with
      500 mg once weekly. After 2 weeks of amifostine therapy, hematopoiesis began to
      improve. In the subsequent 2 months, the patient became completely independent of
      the platelet transfusions; the transfusion frequency of RBC was permanently
      reduced (2 RBC transfusions/month) and a significant decrease of BM blasts was
      achieved. After 30 weeks of amifostine therapy, the morphology of the MDS
      switched to a chronic myelomonocytic leukemia (CMML)-like appearance, with
      continuously increasing leukocytes, so that we discontinued amifostine therapy
      for 1 month to exclude a possible side effect of amifostine. At that time,
      leukocytes further increased to 74,000/microl; thus, we decided to perform a
      cytoreductive chemotherapy (hydroxycarbamide) and continued weekly amifostine
      infusions. During 1 year of amifostine therapy, the patient had a good quality of
      life, with no need for hospitalization and a complete cytogenetic remission. We
      conclude that, in this case, amifostine had two effects: a significant
      improvement of impaired hematopoiesis and a slowing down of disease progression.
      Thus, amifostine might be a therapeutic option in older patients with advanced
      MDS.

PMID- 11233779
TI  - Myeloid/natural killer cell precursor blast crisis of chronic myelogenous
      leukemia with two Philadelphia (Ph-1) chromosomes.
AB  - We report on a 30-year-old patient with blast crisis of a chronic myelogenous
      leukemia (CML) that shows immunophenotypic features similar to those of the
      myeloid/natural killer (NK) cell precursor leukemia previously described.
      Expression of CD13/CD33/CD65 as well as MPO+/LF- blasts was classified as a
      myelogenous blast crisis of a CML. In addition, the blasts were positive for
      CD7/CD56. Other lymphoid markers were not expressed. Cytogenetic and molecular
      cytogenetic examinations showed two Philadelphia (Ph-1) chromosomes and a trisomy
      8. Similar to expression of the myeloid/NK cell precursor phenotype in acute
      myelogenous leukemia (AML), it is possible to exhibit this phenotype in Ph-1
      positive CML. Only one case report of myeloid/NK precursor phenotype blast crisis
      of CML was found in the literature. Therefore, it is not clear whether this
      phenotype is a distinct biologic and clinical disease entity of CML, as is the
      case in the respective AML phenotype.

PMID- 11233780
TI  - Serum thrombopoietin concentration and peripheral platelet counts in essential
      thrombocythemia.

PMID- 11233781
TI  - Predominantly BCR-ABL negative myeloid precursors in interferon-alpha treated
      chronic myelogenous leukemia: a follow-up study of peripheral blood colony
      forming cells with fluorescence in situ hybridization.
AB  - The mechanism and target cell of the life-prolonging effect of interferon-alpha
      (IFN-alpha) in chronic myelogenous leukemia (CML) are controversial. We studied
      the influence of IFN-alpha treatment on the frequency of malignant hematopoietic
      precursor cells in the peripheral blood (PB) of CML patients during the course of
      the disease. PB 10-day colony-forming cells (PB-CFCs) were assessed with regard
      to their quantity, lineage distribution, and BCR-ABL status, as determined by
      fluorescence in situ hybridization (FISH). PB-CFC numbers were determined in 39
      patients (29 in the chronic phase, 6 in an advanced stage, and 4 with progression
      to an advanced stage during follow-up). Thirty-one patients were evaluated either
      once or several times to determine the BCR-ABL status of the colonies. BCR-ABL
      negative PB-CFCs were detectable at diagnosis in 5 of 11 patients. A major
      reduction of BCR-ABL positive colonies to <25% of PB-CFCs was observed in 10/13
      determinable IFN-alpha treated patients in early and late chronic phases,
      indicating a high proportion of BCR-ABL negativity at the clonogenic cell level.
      In contrast, only 3 of these patients had a cytogenetic response of <25%
      Philadelphia chromosome (Ph1)-positive metaphases in bone marrow cytogenetics.
      Treatment with IFN-alpha and/or hydroxyurea (HU) during chronic phase was
      accompanied by a reduction of PB-CFCs to subnormal levels (median 24 CFCs/ml)
      compared to controls (median 207 CFCs/ml), untreated patients in chronic phase
      (median 25,979 CFCs/ml), and patients with advanced disease (median 6,047
      CFCs/ml). In blast crisis (6 patients), all colonies tested were BCR-ABL
      positive. Our results show that IFN-alpha treatment leads to a marked reduction
      of malignant myeloid precursor cells in the PB of CML patients, which exceeds the
      degree of cytogenetic remission. This offers an explanation for the good
      therapeutic efficacy and even life-prolonging effect of IFN-alpha, which is also
      observed in cytogenetic non-responders.

PMID- 11233782
TI  - Expression of 3beta-hydroxysteroid dehydrogenase, cytochrome p450 17alpha
      hydroxylase/17,20-lyase and cytochrome p450 aromatase enzymes in corpora lutea of
      diestrous and early pregnant mares.
AB  - In the pregnant mare, luteal estrogen production increases at the onset of equine
      chorionic gonadotropin (eCG) secretion by endometrial cups. In previous studies,
      we have demonstrated that eCG stimulates luteal androgen and estrogen production
      in pregnant mares. To further elucidate the regulation of steroidogenesis within
      the equine corpus luteum (CL) of pregnancy, we examined the expression of 3beta
      hydroxysteroid dehydrogenase (3beta-HSD), cytochrome P450 17alpha
      hydroxylase/17,20 lyase (P450(17alpha)) and cytochrome P450 aromatase
      (P450(arom)) in luteal tissue samples collected during diestrus (Days 7 to 10)
      and pregnancy before (Days 29 to 35) and after (Days 42 to 45) the onset of eCG
      secretion. Immunoblot analyses revealed a single protein per enzyme with
      molecular weights of 48 kDa (3beta-HSD), 58 kDa (P450(17alpha)) and 56 kDa
      (P450(arom)). Steady-state levels of 3beta-HSD were lower in luteal tissue of
      diestrus than pregnancy, but expression did not change during pregnancy. Steady
      state expression of P450(17alpha) in CL of diestrus was not significantly
      different from that of pregnancy. During pregnancy, P450(17alpha) expression was
      significantly higher after the onset of eCG secretion. Steady-state expression of
      P450(arom) in CL of diestrus was not significantly different from that of
      pregnancy. During pregnancy, luteal expression of P450(arom) was significantly
      lower after the onset of eCG secretion. These data support the hypotheses that
      eCG has a differential effect on the expression of luteal steroidogenic enzymes,
      that the eCG-induced increase in luteal estrogen production is the result of an
      increase in available aromatizable androgen due to an increase in P450(17alpha)
      expression and activity, and that increased luteal estrogen production is not due
      to an increase in aromatase expression.

PMID- 11233783
TI  - Effect of subclinical uterine infection on cervical and uterine involution,
      estrous activity and fertility in postpartum buffaloes.
AB  - Nili-Ravi buffaloes (n=29) that calved normally between August and November and
      did not develop any clinical reproductive disorder after calving were studied for
      the incidence of sub-clinical bacterial infection of the uterus and its effects
      on postpartum reproductive efficiency. The incidence of subclinical uterine
      infection was 24% (7/29). Involution of the cervix and uterus was slower (P <
      0.01) in the infected group than in the normal group (45.6 vs 31.1 days and 46.3
      vs 35.8 days), respectively. The mean diameters of cervix and gravid horn on Day
      12 post partum and on completion of involution did not differ between buffaloes
      of the two groups. However, the rate of involution of the cervix and the gravid
      horn was lower in buffaloes of the infected group (2.2 vs. 2.7 mm/day and 2.6 vs.
      3.2 mm/day). The mean interval to first post partum ovulation was similar in
      buffaloes in the infected (35.5 days) and the normal group (33.8 days). The life
      span of corpus luteum formed after first ovulation was shorter (11 days) in
      buffaloes of both groups than that of a normal estrous cycle (15 to 17 days). The
      incidence of silent ovulation was apparently higher in buffaloes of the infected
      group (83 vs. 60%) but the difference was not significant. For the first four
      months after calving, the mean interval to first postpartum estrus was longer in
      buffaloes of the infected group (73.0 vs. 47.7 days; P < 0.01). Similarly, the
      average service period was longer in buffaloes of the infected group (91.0 vs.
      64.8 days; P < 0.05). The overall pregnancy rate for the first four months after
      calving did not differ between buffaloes of the two groups. We conclude that
      subclinical bacterial infection of the postpartum uterus delays the cervical and
      uterine involution which can, in turn, delay the occurrence of first postpartum
      estrus and prolong the service period in buffaloes.

PMID- 11233784
TI  - Effects of brief postponement of the preovulatory LH surge on ovulation rates and
      embryo formation in eCG/prostaglandin-treated heifers.
AB  - The aim of this study was to investigate whether prolongation of the period of
      preovulatory follicular development after superovulation reduces heterogeneity of
      oocytes of stimulated follicles with respect to the potential to mature, to
      ovulate, to be fertilized and to develop into embryos. Heifers were treated with
      eCG on Day 10 and prostaglandin (PG) 48 h later. At the time of eCG
      administration some of the heifers received a norgestomet implant (N) to suppress
      the LH surge. After 96 to 104 h, N was removed and an LH surge was induced with
      GnRH (G) (N/G); the other animals served as controls. Matured oocytes (Experiment
      A: n=9, 139 [N/G] and 11, 125 [Control] heifers, oocytes), zygotes and oviducts
      (Experiment B: n=8, 44 [N/G] and 9, 72 [Control] heifers, zygotes) and embryos
      (Experiment C: n=11, 205 [N/G] and 11, 165 [Control] heifers, embryos) were
      collected at 22 to 26 h, 38 to 52 h and 7 days after the LH surge, respectively.
      Hatched blastocyst formation of matured oocytes (Experiment A) was analyzed after
      11 days of IVC after IVF. In vivo fertilization rate of zygotes, the presence of
      periodic acid-Schiff (PAS) positive granules in the oviduct (Experiment B) and
      stage of development of embryos (Experiment C) were analyzed
      stereomicroscopically. The mean interval between PG and the LH surge was 53.8+/-3
      (SD) (N/G) vs. 42.4+/-4 h (Control). The maximum peripheral estradiol-17beta
      concentration (529+/-36 [SEM] [N/G] vs. 403+/-17 pmol/L [Control]) and the
      response to superovulation (25.4+/-2 [N/G] vs. 18.7+/-2 [Control]) were higher in
      N/G than in Control heifers. Hatched blastocyst formation rate (37.4 [N/G] vs.
      33.6% [Control]), in vivo fertilization rate (69.0+/-14 [N/G] vs. 73.0+/-10%
      [Control]) and the yield of total embryos (3.8+/-1 [N/G] vs. 5.6+/-2 [Control])
      did not differ between groups. The percentage of heifers with abundant PAS
      positive granules in the distal ampulla (0 [N/G] vs. 31% [Control]) was reduced
      after N/G treatment. Prolongation of the period of preovulatory follicular
      development increased the number of mature follicles and ovulations but did not
      result in higher embryo yield, possibly because of an impaired oviductal
      environment.

PMID- 11233786
TI  - Cryopreservation of equine embryos by open pulled straw, cryoloop, or
      conventional slow cooling methods.
AB  - Cryopreservation of equine embryos with conventional slow-cooling procedures has
      proven challenging. An alternative approach is vitrification, which can minimize
      chilling injuries by increasing the rates of cooling and warming. The open pulled
      straw (OPS) and cryoloop have been used for very rapid cooling and warming rates.
      The objective of this experiment was to compare efficacy of vitrification of
      embryos in OPS and the cryoloop to conventional slow cool procedures using 0.25
      mL straws. Grade 1 or 2 morulae and early blastocysts (< or = 300 microm in
      diameter) were recovered from mares on Day 6 or 7 post ovulation. Twenty-seven
      embryos were assigned to three cryopreservation treatments: (1) conventional slow
      cooling (0.5 degrees C/min) with 1.8 M ethylene glycol (EG) and 0.1 M sucrose,
      (4) vitrification in OPS in 16.5% EG, 16.5% DMSO and 0.5 M sucrose, or (3)
      vitrification with a cryoloop in 17.5% EG, 17.5% DMSO, 1 M sucrose and 0.25
      microM ficoll. Embryos were evaluated for size and morphological quality (Grade 1
      to 4) before freezing, after thawing, and after culture for 20 h. In addition,
      propidium iodide (PI) and Hoechst 33342 staining were used to assess percent live
      cells after culture. There were no differences (P > 0.1) in morphological grade
      or percent live cells among methods. Mean grades for embryos after culture were
      2.9 +/- 0.2, 3.1 +/- 0.1, and 3.3 +/- 0.2 for conventional slow cooling, OPS and
      cryoloop methods, respectively. Embryo grade and percent live cells were
      correlated, r = 0.66 (P < 0.004). Thus OPS and the cryoloop were similarly
      effective to conventional slow-cooling procedures for cryopreserving small equine
      embryos.

PMID- 11233785
TI  - Development and de novo protein synthetic activity of bovine embryos produced in
      vitro in different culture systems.
AB  - In vitro matured (IVM) and fertilized (IVF) putative Day 1 zygotes (Day 0 = IVF)
      were allocated randomly to culture in formulations based on Synthetic Oviduct
      Fluid (SOF) medium and identified on the basis of their contrasting principal
      supplements, which were 10% v/v steer serum (SS; n = 558) or 4 mg/mL crystalline
      BSA (SBSA; n = 531) or 3 mg/mL polyvinyl alcohol (SPVA; n = 607) in 9 replicates.
      SBSA and SPVA also contained 10 microg/mL non-essential amino acids, while the
      former was further supplemented with 20 microL/mL essential amino acids and the
      latter with 0.5 mmol/L sodium citrate and 5 ng/mL epidermal growth factor.
      Zygotes were cultured in 20 microL drops (4 zygotes per drop) until Day 8 in an
      atmosphere of 5% CO2, 5% O2 and 90% N2 at 39 degrees C and droplets were renewed
      every 48 hours. The incidence of zygote cleavage was lower (P < 0.05) in SS (mean
      +/- SEM = 61 +/- 3%) than in SBSA (76 +/- 3%) but not in SPVA (72 +/- 4%) up to
      Day 3. The SPVA generated a lower yield of blastocysts on Day 7 (12 +/- 2%; P <
      0.001) and by Day 8 (21 +/- 4%; P < 0.01) than did SS (33 +/- 3%; 40 +/- 3%) and
      SBSA (30 +/- 3%; 37 +/- 4%). Cell numbers (n) and diameters (d) of blastocysts on
      Day 8 were greater (P < 0.001; Replicates 1 to 5) in embryos from SBSA (n, 156 +/
      9; d, 203 +/- 4 microm) than in those from SS (n, 81 +/- 4; d, 177 +/- 3 microm)
      and SPVA (n, 76 +/- 5; d, 167 +/- 3 microm). Embryos produced in SS incorporated
      less 3H-phenylalanine into PCA-precipitable protein (replicates 6 to 9; log10 dpm
      = 3.03 +/- 0.04) than did embryos cultured in SBSA (3.21 +/- 0.03; P < 0.001) or
      in SPVA (3.14 +/- 0.03; NS). In conclusion, blastocyst yield was poor in SPVA,
      but the embryos had metabolic activities similar to those of embryos produced in
      SBSA. Blastocyst yields from SS were not compromised but their capacity for de
      novo protein synthesis was reduced significantly.

PMID- 11233787
TI  - Protection of boar spermatozoa from cold shock damage by 2-hydroxypropyl-beta
      cyclodextrin.
AB  - This study examined whether 2-hydroxypropyl-beta-cyclodextrin (HBCD) could play a
      role in protecting spermatozoa from cold shock, as judged by motility parameters,
      intact acrosomes, and membrane integrity. Motility parameters were assessed by a
      computer-assisted sperm motility analysis (CASA) system, and the acrosome and
      membrane integrity were evaluated by fluorescent staining with FlTC-labeled
      peanut agglutinin and SYBR-14 plus Propidium Iodide, respectively. The addition
      of HBCD to the BF5 extender significantly increased the percentages of
      spermatozoa with intact acrosomes and increased membrane integrity after cold
      shock. The motility, progressive motility, and progressive velocity of the cold
      shocked spermatozoa in the presence of HBCD were significantly higher than in the
      absence of HBCD. In contrast, further supplement of HBCD with cholesterol-3
      sulfate (a cholesterol analogue) resulted in a decrease in all the aforementioned
      criteria, suggesting that the ability of HBCD to protect spermatozoa from cold
      shock injury is blocked by saturating the cholesterol binding sites of HBCD. It
      is therefore concluded that HBCD protects spermatozoa against cold shock injury,
      possibly due to its ability to remove membrane cholesterol.

PMID- 11233788
TI  - Physical properties of bovine cervical mucus during normal and induced
      (progesterone and/or PGF2alpha) estrus.
AB  - Ninety two Friesian cows were used to determine physical properties of cervical
      mucus collected during normal estrus and estrus induced. Estrus was induced using
      either progesterone (P4) releasing intravaginal devices (PRID) and/or
      prostaglandin F2alpha (PGF2alpha). The animals were assigned to 4 groups (no
      treatment, a PRID for 12 days plus an injection of 1000 IU PMSG at the removal of
      the PRID, a double injection of 3 mL PGF2alpha 11 days apart, and a PRID for 7
      days plus an injection of PGF2alpha 24 h before the removal of PRID). A number of
      cows with normal estrus exhibited three consecutive estrus cycles after calving.
      Cows that had not shown estrus for three months after calving had their
      reproductive system palpated twice at 10-day intervals, to determine their
      ovarian activity. Then PRID and/or PGF2alpha was administered to cows that were
      found to have a palpable corpus luteum in one of two palpations (cycling cows).
      The cows of the three induced estrous groups were artificially inseminated (AI)
      twice, while those with normal estrus received only a single AI. Cervical mucus
      samples were collected from all cows 5 to 30 min before the first AI.
      Additionally, samples of cervical mucus were collected from 20 cows at their
      first estrus after the induced estrus. The results are summarized as follows: 1)
      The physical properties of cervical mucus were similar in the first three normal
      consecutive estrus cycles after calving. 2) The physical properties of cervical
      mucus in normal estrus after calving were similar to those in the first estrus
      after an induced estrus. 3) The pH values for normal estrus were similar to those
      for induced estrus. 4) Viscosity of cervical mucus in the normal estrous group
      was significantly lower than that in the induced estrus. Furthermore, significant
      differences were noticed among the three induced estrous groups. 5) Spinnbarkeit,
      crystallization and receptivity of cervical mucus (penetration test) were
      significantly higher in the normal estrous group than in the induced estrous
      groups, while no difference was detected among induced estrus groups. 6)
      Pregnancy rates in the normal estrus group were the same as in the induced estrus
      groups. 7) The percentages of cows in the induced estrous groups that produced
      cervical mucus with similar viscosity, spinnbarkeit and receptivity (penetration
      test) characteristics as the normal estrus group, was very low.

PMID- 11233789
TI  - Experimental collection and transfer of embryos from bovine immunodeficiency
      virus (BIV) infected cattle.
AB  - Three experiments were conducted to determine whether the lentivirus, bovine
      immunodeficiency virus (BIV) is likely to be transmitted via embryo transfer. In
      the first experiment, embryos collected from BIV-negative heifers were exposed in
      vitro to BIV for 24 h, washed and then tested for the presence of the provirus.
      In the second experiment, embryos obtained from BIV-negative heifers were
      transferred to the uterine horns of BIV-infected heifers; 24 h later these
      embryos were recovered and tested for the presence of BIV. In the third
      experiment, embryos were collected from heifers experimentally infected with BIV
      and then transferred to BIV-negative recipients. In all three experiments, (BIV)
      proviral DNA was not detected by PCR in association with any oocytes, embryos,
      follicular fluid, oviductal or uterine washes. Twelve single embryos collected
      from BIV experimentally infected donors were transferred to BIV-negative
      recipients resulting in the birth of 7 calves all of which were also negative for
      BIV; the recipients remained BIV-negative throughout the experiment. In
      conclusion, this study demonstrates that it is possible to produce transferrable
      stage embryos from donors infected with BIV and that such embryos are unlikely to
      transmit this agent either to the recipients or the resulting offspring.

PMID- 11233790
TI  - Successful in vitro production of embryos in the red deer (Cervus elaphus) and
      the sika deer (Cervus nippon).
AB  - The aim of our study was to define the conditions for IVM and IVF of oocytes in 2
      common deer species as models for endangered related subspecies. Immature oocytes
      were recovered during the breeding season from postmortem ovaries (red deer) or
      by repeated laparoscopic follicular aspiration (sika deer). Oocytes were cultured
      for 24 h in IVM medium supplemented with EGF or FSH and follicular fluid. Stag
      semen was collected by electroejaculation (both species) or by epididymal
      flushing (red deer) and cryopreserved. For IVF, oocytes were exposed to different
      concentrations of thawed spermatozoa in a modified Tyrode albumin lactate
      pyruvate medium supplemented with 20% (v/v) estrus sheep serum for 18 h. After
      IVF, presumptive zygotes were allowed to develop in vitro for 7 days in synthetic
      oviduct fluid (SOF) supplemented with fetal calf serum (10%, v/v). In both
      species, the presence of ovine FSH and follicular fluid improved the in vitro
      maturation rate. In the sika deer, the optimal sperm concentration for IVF was
      10(6)/mL and some fertilized oocytes reached the early morula stage (20 to 25
      cells). In the red deer, after IVF with ejaculated or epididymal spermatozoa (2.0
      x 10(6)/mL), 20% of zygotes developed to the blastocyst stage (50 to 80 cells).

PMID- 11233791
TI  - Immune regulation of ovarian function in buffaloes (Bubalus bubalus).
AB  - We studied the infiltration of different subsets of immune system cells in the
      ovarian parenchyma of Egyptian buffaloes during follicular and luteal phases of
      the estrous cycle. All subsets of leukocytes infiltrated significantly more into
      corpora lutea (CL) than into Graafian follicles (GF) (P < 0.01) except for plasma
      cells that were abundant in the GF but not observed in the CL. The number of
      macrophages, lymphocytes, neutrophils and eosinophils were significantly greater
      in mature CL than in corpora hemorrhagica (CH) or regressing CL. Moreover, the
      regressing CL showed significantly more macrophages, lymphocytes and neutrophils
      than the CH. Large antral follicles were infiltrated with larger number of
      leukocytes than growing preantral atretic follicles. Macrophages and neutrophils
      observed in large antral follicles were significantly more abundant in the theca
      externa than the theca interna (P < 0.01). Only plasma cells were significantly
      greater in number in the theca intema (P < 0.01). Leukocytes infiltrated
      significantly more into large mature follicles than large, growing, preantral
      atretic follicles (P < 0.01). Results of this study reveal the calling of
      leukocytes in a significant numbers inside the ovarian tissue of buffaloes around
      the time of ovulation and at luteolysis. It is possible that leukocytes with
      their powerful bioactive cytokines (IL-1, TNFalpha, GM-CSF, and INF-gamma) may
      assist in ovarian functions such as ovulation and luteolysis.

PMID- 11233792
TI  - Long-term preservation of chilled canine semen: effect of commercial and
      laboratory prepared extenders.
AB  - The present study was conducted to evaluate chilled semen conservation over time
      in 3 commercial and 4 laboratory prepared extenders, including a new Tris-glucose
      extender. The beneficial effect of adding egg yolk to these media was also
      analyzed. The effects of these extenders on motility and acrosome reaction were
      characterized objectively using a computer-aided semen analyzer and the
      chlortetracycline staining, respectively. No significant differences were
      observed when comparing the different commercial extenders without egg yolk, but
      addition of egg yolk improved all motility parameters significantly (preservation
      of 50% of motility was observed at 3.2+/-1, 2.9+/-0.5, 2.3+/-0.5, 8.5+/-0.2,
      5.4+/-1.1, 5.2+/-0.4 d, for Biladyl, green extender and fresh-phos extenders
      without and with egg yolk, respectively). Motility parameters were best preserved
      in egg yolk supplemented Biladyl extender with a mean percentage of 86.3+/-10.5
      motile spermatozoa after 7 d at 4 degrees C. Efficacy of egg yolk-supplemented
      commercial extenders on sperm motility at 4 degrees C was (in decreasing order)
      as follows: Biladyl > green extender > fresh-phos. However, high quality motility
      and the percentage of motile spermatozoa were highest with some of the laboratory
      prepared extenders: a 50% conservation rate of motile spermatozoa was observed
      following the use of supplemented egg yolk extenders. These are classified in
      decreasing order as follows: Tris-glucose (13+/-1 d) > Tris-fructose (9.7+/-0.6)
      > EDTA (4.+/-0.6 d) > Tris-bes (3.6+/-1.1 d). A low concentration of motile
      spermatozoa was still observed in the Tris-glucose egg yolk extender 16 d after
      collection, clearly demonstrating the importance of the medium and the beneficial
      effect of egg yolk on sperm motility of 4 degrees C chilled semen. Similar
      effects of extender were observed for acrosome reactions. Egg yolk clearly had a
      protective effect reducing acrosome reactions significantly in all media tested
      as follows: the highest acrosome losses were observed in the fresh-phos and EDTA
      extenders without egg yolk; the lowest rate was observed with Tris-glucose
      supplemented egg yolk extender. In conclusion, at 4 degrees C, egg yolk extender
      best-protected sperm motility parameters. Differences in osmolarity between the
      extenders in terms of substrate related to sperm metabolic activity may explain
      the optimal results obtained using egg yolk-supplemented Tris-glucose extender,
      which preserved motility and acrosome integrity in chilled dog semen. These
      results indicated that good quality dog spermatozoa could be preserved for up to
      10 d.

PMID- 11233793
TI  - Correlation between the spermatozoal characteristics and sperm penetration
      distance in polyacrylamide gel and bovine cervical mucus.
AB  - Correlation between the spermatozoal characteristics and the sperm penetration
      distance in polyacrylamide gel was assessed, utilizing frozen thawed semen
      samples obtained from 6 bulls, and it was compared with the correlation between
      sperm penetration in bovine cervical mucus and spermatozoal characteristics. In
      vitro sperm penetration tests were performed with mucus and gel. The sperm
      penetration in gel and mucus was significantly and positively correlated with
      post-thaw motility (r=0.81; r=0.89:P<0.01) and acrosome integrity (r=0.88;
      r=0.94:P<0.01). A significant negative correlation with abnormal spermatozoa (r=
      0.84;r=0.83:P<0.01) was observed. Both sperm concentration and post-thaw live
      spermatozoa were not significantly correlated. A significant multiple regression
      between sperm penetration and the spermatozoal characteristics both in gel
      (R2=0.87; F=40.27; P<0.01) and mucus (R2=0.91; F=60.48; P<0.01) was observed. The
      major spermatozoal characteristics determining the capacity of spermatozoa to
      penetrate gel were post-thaw motility, percentage of abnormal spermatozoa and
      acrosome integrity. The acrosome integrity has a more significant contribution.
      The correlation established with sperm penetration in gel was very similar to
      that of sperm penetration in mucus. The utility of gel as a mucus substitute in
      in vitro sperm penetration tests was discussed.

PMID- 11233794
TI  - Failure of cidofovir to reduce CMV-antigenemia in a child transplanted from a
      matched unrelated donor.

PMID- 11233795
TI  - Immunotherapy: on the edge between experimental and clinical oncology.
AB  - Cancer immunotherapy is still largely confined to the laboratory bench and
      experimental animal models. Yet the field is rapidly moving forward and some
      immunological tools are now entering into clinical use. The first and perhaps
      best example of such progress is given by bioengineered humanized monoclonal
      antibodies of which some have been already approved for therapy in B-cell
      lymphoma and breast cancer. Unexpectedly, another remarkable form of
      immunotherapy has turned out to derive from T-cell adoptive therapy associated
      with allogeneic bone marrow transplantation. Its benefits render such an approach
      the first choice therapy for a large number of hematological malignancies and it
      is now being adapted also for treatment of advanced solid tumors. Finally,
      harnessing the immune system against the autologous tumor remains the most
      ambitious but still distant design for immunotherapy. Recent technical advances
      and a better understanding of the immune system in cancer patients should concur
      in defining the best strategy for active immunotherapy in clinical oncology.

PMID- 11233797
TI  - Immunomodulation by macrolide antibiotics.
AB  - Macrolide antibiotics are strongly concentrated within host cells, a property
      that sustains their activity against intracellular pathogens and is likely
      responsible for the modulation of cell metabolism and function. There is
      extensive literature on the subject of macrolide-induced modulation of immune
      responses. Erythromycin A derivatives seem to display anti-inflammatory activity
      in vitro, in some animal models and in various clinical settings such as diffuse
      panbronchiolitis (DPB). The underlying mechanisms are not yet fully understood:
      inflammatory cytokine and oxidant production by phagocytes is down-regulated by
      these drugs, but other possible targets include bacterial virulence factors,
      bronchial and epithelial cells, etc. Also, a link has been suggested between the
      macrolide transmembrane carrier system and the P-glycoprotein family, which
      comprises MDR (multiple drug resistance) and CFTR (cystic fibrosis transmembrane
      conductance regulator), which are respectively involved in the chemotherapeutic
      resistance of cancer cells and in the genesis of cystic fibrosis.

PMID- 11233796
TI  - Comparison of five different methods for detection of SHV extended-spectrum beta
      lactamases.
AB  - Five different methods for detection of different types of SHV extended-spectrum
      beta-lactamases (ESBL) were compared: minimum inhibitory concentration (MIC)
      determination of beta-lactam with and without clavulanic acid, double-disk
      synergy test (DDST), inhibitor potentiated disk diffusion test (IPDDT), three
      dimensional test (TDT) and PCR/Nhe I test. MIC determination of beta-lactam with
      and without clavulanic acid was the most sensitive method regardless of the type
      of beta-lactamase. However the specificity of this method was a little above 90%.
      IPDDT turned out to be a very sensitive method too but it lacks specificity
      because 26.9% of ceftazidime sensitive strains (putative ESBL negative), gave a
      positive result. It is important to put all four disks on the plate because
      ceftazidime and aztreonam were more sensitive indicators for SHV-5 and SHV-12
      beta-lactamase producers while cefotaxime and ceftriaxone were more reliable in
      detecting SHV-2 beta-lactamase producers. The DDST detected all SHV-5 and SHV-12
      beta-lactamase producers and 95.2% of SHV-2, so it was less sensitive than MIC
      determination but was highly specific, since there were no false negative results
      observed. The sensitivity of DDST can be improved by using all four disks and
      placing them at the smaller distance from the central disk (2.5 cm). The TDT was
      the least sensitive method, particularly for SHV-5 and SHV-12 beta-lactamase
      producers. The PCR/Nhe I test for detection of ESBL blaSHV genes is a highly
      sensitive and specific method but it is rather laborious and thus not very
      practical for use in routine clinical laboratories. Nevertheless it has potential
      to serve as the gold standard in epidemiological investigations on ESBLs.
      According to the results of this investigation MIC determination of beta-lactam
      with and without clavulanic acid, even if only one antibiotic is used and the
      PCR/Nhe I tests are the most reliable methods for detection of SHV ESBLs.

PMID- 11233798
TI  - New Staphylococcus aureus incompatibility group 1 plasmids encoding penicillinase
      production and resistance to different antibacterial agents.
AB  - Eleven Staphylococcus aureus plasmids encoding penicillinase production and
      resistance to different antibacterial agents were transferred to laboratory
      recipient strains in mixed-culture transfer and transduction experiments and
      characterized by restriction endonuclease analysis and incompatibility. The
      plasmids were differentiated into four types (types A-D) on the basis of their
      resistance phenotypes and restriction endonuclease patterns. One type encoded
      resistance to cadmium and arsenate. The second type encoded resistance to
      cadmium, mercuric compounds and nucleic acid-binding compounds. The third type
      encoded resistance to cadmium, kanamycin, neomycin and streptomycin while the
      fourth type encoded resistance to kanamycin, neomycin and ethidium bromide.
      Plasmids within the same class were structurally related or similar and were
      different from those in the other classes. Three plasmids, pWBG626, pWBG628, and
      pWBG663, representing three of the four plasmid types, belonged to
      incompatibility group 1. These new plasmids add to the number of known
      incompatibility group 1 plasmids and have resistance phenotypes which should be
      useful for studying incompatibility of new S. aureus plasmids.

PMID- 11233799
TI  - Determination of minumum inhibitory concentrations of Candida species isolated
      from vaginal swab specimens by using broth macrodilution and E-test.
AB  - The purpose of the present study was to evaluate the utility of the E-test in
      determining the antifungal susceptibility of Candida species. A total of 50
      Candida strains, including 34 Candida albicans and 16 non-albicans were isolated
      from vaginal swab specimens from women suffering from vaginitis. The minimum
      inhibitory concentrations (MICs) of amphotericin B, fluconazole and ketoconazole
      were detected by using broth macrodilution and the E-test. When the results of
      the two tests were compared, the MIC values were considered acceptable if the
      difference between the two assays was no more than two-fold (+/-1dilution). The
      acceptable rates were: 84% for amphotericin B, 97% for fluconazole and 78% for
      ketoconazole. Finally, MICs of C. albicans against the tested antifungal agents
      were generally lower than for non-albicans strains. These results suggest that
      the E-test can be used for the determination of MIC values for Candida species
      isolates.

PMID- 11233800
TI  - Impact of gemifloxacin on the normal human intestinal microflora.
AB  - Gemifloxacin is a new fluoroquinolone that has been shown to possess a broad
      spectrum of antimicrobial activity against gram-positive and gram-negative
      microorganisms including methicillin-susceptible and methicillin-resistant
      staphylococci, Streptococcus pneumoniae, Haemophilus influenzae and most members
      of the family Enterobacteriaceae. The aim of the present study was to investigate
      the effect of gemifloxacin on the human intestinal microflora. Gemifloxacin was
      given in oral doses of 320 mg for 7 days to 10 healthy subjects and 5 subjects
      received a once-daily dose of matched placebo for 7 days. Faecal samples were
      collected prior to administration (days -8 and -6), during the administration
      period (days 2 and 4) and after withdrawal of administration (days 8, 11, 21, 28
      and 56). In the aerobic intestinal microflora the numbers of enterobacteria were
      suppressed during the gemifloxacin administration and the numbers of enterococci
      and streptococci were also decreased. No other aerobic microorganisms were
      affected. In the anaerobic microflora the numbers of anaerobic cocci and
      lactobacilli were suppressed during the gemifloxacin administration while no
      other changes occurred. The microflora was normalized 49 days after the
      administration of gemifloxacin had stopped. No selection or overgrowth of
      resistant bacterial strains or yeasts occurred. The ecological impact of
      gemifloxacin was shown to be selective and similar to that of ciprofloxacin,
      levofloxacin and ofloxacin.

PMID- 11233801
TI  - Bacillus Calmette-Guerin down-regulates CD1b induction by granulocyte-macrophage
      colony stimulating factor in human peripheral blood monocytes.
AB  - Non-peptide antigens (e.g. glycolipids of microbial origin) presented by monocyte
      associated CD1 molecules to T cells appear to play an important role in host
      immunity against tuberculosis and other pathogenic bacteria. Since vaccination
      with Bacillus Calmette-Guerin (BCG) has limited efficacy, the influence of viable
      BCG organisms on the induction of CD1b antigen by granulocyte macrophage-colony
      stimulating factor (GM-CSF) has been tested in adherent mononuclear cells
      obtained from peripheral blood of healthy donors. The results indicate that the
      vaccine reduces substantially CD1b induction by GM-CSF. On the other hand, BCG
      was found to promote a slight increase in the expression of this molecule on
      target cells not exposed to GM-CSF. Attempts to reverse the antagonistic effects
      of BCG on GM-CSF with high concentrations of GM-CSF, alone, or associated with IL
      4, were unsuccessful. Moreover, mycobacteria suppression by 10 microg/ml of
      rifampin, did not affect BCG influence on CD1b induction. The present results
      suggest that mycobacterium-induced impairment of the CD1 system could play a role
      in the unsatisfactory results obtained with BCG vaccination.

PMID- 11233802
TI  - Antitrypanosomal properties of cis-platinum-pentamidine bromide, thiocyanate and
      seleniocyanate on Trypanosoma brucei brucei mouse and sheep models.
AB  - Three organometallic complexes derived from pentamidine were evaluated for their
      trypanocidal effect on in vivo Trypanosoma brucei brucei models in comparison to
      pentamidine isethionate as reference compound. On the T. b.brucei mouse model,
      the most active compound was cis-platinum-pentamidine bromide. This compound was
      active when subcutaneously administered at the single dose of 1.5 micromol/kg and
      its chemotherapeutic index was 200 whereas pentamidine isethionate was active at
      6 micromol/kg with a chemotherapeutic index of 13, when administered in the same
      conditions. Cis-platinum-pentamidine bromide was active at 1 mg/kg (1.44
      mmoles/kg), in a single dose by subcutaneous route against the early stage of the
      T. b.brucei Antat 1-9 sheep model. Platinum kinetics in serum showed a Cmax of
      0.2 mg/l reached 80 h after the treatment at this dose. Cis-platinum-pentamidine
      bromide, cis-platinum-pentamidine seleniocyanate, and cis-platinum-pentamidine
      thiocyanate were distributed in the deep compartment according to a
      monocompartmental model. In all cases, platinum was eliminated from the serum 700
      hours post-treatment. All data obtained from these models show activity on the
      early stage of the disease and justify further investigations on the late stage
      of the disease.

PMID- 11233803
TI  - Effect of ketoconazole, itraconazole and fluconazole on the gastrointestinal
      colonization of mice by Candida albicans.
AB  - Crl:CD1 (ICR) BR mice were colonized in the gastrointestinal (GI) tract with
      Candida albicans. This strain was susceptible to ketoconazole (MIC=0.25
      microg/ml), itraconazole (minimum inhibitory concentration, MIC=0.25 microg/ml),
      and fluconazole (MIC=4 microg/ml). Subsequently the animals received monotherapy
      with ketoconazole by mouth (equivalent to human dose of 2.9 mg/kg/day), or
      itraconazole by mouth (equivalent to human dose of 2.9 mg/kg/day), or fluconazole
      either subcutaneously (equivalent to human dose of 2.2 mg/kg/day), or by mouth
      (equivalent to human dose of 2.2 mg/kg/day), for 10 days. Quantitative stool
      cultures at the end and one week after the end of treatment revealed that all
      three azoles caused a small and statistically non significant reduction of C.
      albicans concentration in the stools. The different route of administration of
      fluconazole did not produce different results. In conclusion, these azoles, used
      at the present doses and schedules, have minimal effect on murine GI colonization
      by this strain of C. albicans which is susceptible but with rather increased
      MICs.

PMID- 11233804
TI  - Efficacy of meropenem as monotherapy in the treatment of ventilator-associated
      pneumonia.
AB  - We performed a prospective, open label, randomized study in intensive care unit
      patients with ventilator-associated pneumonia (VAP) to determine the efficacy and
      safety of empiric intravenous (i.v.) meropenem monotherapy compared with the
      combination of ceftazidime plus amikacin. A total of 140 patients receiving
      mechanical ventilation and diagnosed with pneumonia were included in the study.
      Patients were randomized to receive either 1 g meropenem i.v. every 8 hours or 2
      g ceftazidime i.v. every 8 hours plus 15 mg/kg amikacin daily, administered to
      patients with normal renal function as two daily doses. Satisfactory clinical
      responses (cure or improvement) were achieved at the end of treatment in 68.1% of
      meropenem-treated patients and 54.9% in the ceftazidime/amikacin-treated group
      (relative risk 1.25; 95% confidence interval >1.00, 1.55). When non-evaluable
      patients were excluded from the analysis, the satisfactory clinical response was
      82.5% and 66.1% for the meropenem and ceftazidime/amikacin patients, respectively
      (p = 0.044). Logistic regression demonstrated that treatment with meropenem and
      both the basic traumatic and medical pathologies were significantly associated
      with a satisfactory response. Adverse events judged to be possibly or probably
      related to treatment were reported by seven (10.1%) patients in the meropenem
      group and by eight patients (11.3%) in the ceftazidime/amikacin group. The
      results of this study confirm that monotherapy with meropenem is well tolerated
      and provides superior efficacy to the conventional combination of ceftazidime and
      amikacin in combating VAP.

PMID- 11233805
TI  - The role of lomefloxacin in the treatment of chronic prostatitis.
AB  - The choice of antimicrobial agents for treatment of prostatitis should be based
      on two factors: in vitro sensitivity of isolated pathogens and potential
      intraprostatic penetration of the molecule. Unfortunately, only a few antibiotic
      agents penetrate prostatic fluid which is the primary site of infection.
      Lomefloxacin, a once-daily difluoroquinolone, could play a central role in the
      therapy of prostatitis because it has sufficient liposolubility, low ionization
      (pKa), low protein binding, small molecular size, long serum elimination half
      life and it can pass from interstital fluid across prostatic cells into the
      lumen. This study was carried out on 12 patients (mean age 65 years) with normal
      hepatic and renal function, divided into two groups of 6 subjects each.
      Lomefloxacin was administered for perioperative antisepsis at the dose of 400 mg
      orally once a day for 4 days. Serum and tissue were sampled in the two groups of
      patients 4 h (Group A) and 8 h (Group B) respectively after the last drug
      administration. Tissue penetration was higher than serum, with a T/S >2 in the
      prostatic capsule and seminal blister, and a T/S >1.6 in the adenomatous tissue,
      in both groups of patients. In addition, the prostatic tissue concentrations
      exceeded the MIC for the main pathogens usually involved in urogenital
      infections. Therefore, because of its pharmacokineitic and pharmacodynamic
      characteristics, lomefloxacin is proposed as an efficacious therapeutic option,
      even for the treatment of chronic prostatitis.

PMID- 11233806
TI  - Combination of paclitaxel and etoposide in the treatment of advanced non-small
      cell lung cancer: a phase I-II study.
AB  - Thirty-six patients (pts) with unpretreated advanced non-small cell lung cancer
      (NSCLC) stages IIIB and IV were enrolled in this two-stage phase I-II study aimed
      to establish the maximum tolerated dose (MTD) of paclitaxel and to evaluate the
      efficacy and safety of paclitaxel combined with etoposide every 3 weeks for a
      maximum of 6 courses, increasing the dose of paclitaxel according to a modified
      Fibonacci scheme. Nineteen pts were enrolled in the first stage and 17 pts in the
      second stage. The characteristics of the pts were as follows: median age 56 years
      (40-70), median Karnofsky's Performance Status 80% (70-80), 11 pts were stage
      IIIB and 25 pts stage IV. The doses of etoposide administered were 50 mg/m2 for
      15 pts and 100 mg/m2 for 21 pts. MTD has not been reached and the study proceeded
      with the dose of paclitaxel 250 mg/m2. We obtained 9 (25%) partial remissions
      (PR) and 11 (31%) stable disease (SD) in 33 objectively evaluable pts. Median
      time to progression (TTP) was 4 months (0.3-21), median survival was 9.3 months
      (0.3-27). The main toxicity was neutropenia and neurotoxicity, while the
      gastrointestinal toxicity was mild. Two pts deceased after the first course. The
      causes of death were necrotizing enteritis in the first pt and congestive heart
      failure in the second pt. A total of 156 courses were administered at 7 dose
      levels, with a median of 4 courses per patient (1-6). The results seem to support
      the use of this combination in advanced non-small cell lung cancer.

PMID- 11233807
TI  - Antifungal and immunomodulating activities of 1,4-benzothiazine azole
      derivatives: review.
AB  - We reviewed the studies on the in vitro and in vivo antifungal activity of 1,4
      benzothiazine azole derivatives (1,4-BT). A number of different 1,4-BT have been
      tested for anti-Candida activity, investigating their N-4 substitution, sulfur
      oxidation state, presence of the carbonyl group in C-3, insertion of the side
      chain on C-6, C-7 or C-8 of benzothiazine nucleus, the nature of azolic
      substituent (triazole or imidazole), which tend to differ. Moreover, benzoxazine
      analogues have been tested to evaluate the effect of sulfur bioisosteric
      substitution on their activity. We found that their antifungal activity
      correlates with well-defined chemical characteristics including the presence of
      ether substitution at the side chain. In fact, ether derivatives are the most
      active compounds in vivo, although they have little anti-Candida effect in vitro.
      This discrepancy could be attributed to the fact that 1,4-BT are metabolized to
      active antifungal compounds and may have in vivo activity through improvement of
      protective immune response and direct antifungal effects. In fact, 1,4-BT also
      show immunomodulating activity so that the direct antifungal activity, in
      combination with the capability to stimulate the immune response, could result in
      a significant increase in in vivo efficacy.

PMID- 11233808
TI  - Neoadjuvant chemotherapy for high grade osteosarcoma of the extremities: long
      term results for patients treated according to the Rizzoli IOR/OS-3b protocol.
AB  - The results of the Rizzoli IOR/OS-3b neoadjuvant protocol for the treatment of
      osteosarcoma of the extremity are reported. Preoperative chemotherapy consisted
      of two cycles of high-dose methotrexate (HDMTX i.v.), followed by a combination
      of cisplatin (CDP i.a.)/ doxorubicin (ADM i.v.). Postoperatively all patients,
      regardless of the histologic response, received 3 more cycles of MTX, CDP/ADM
      alternated with 3 cycles of ifosfamide. In the study performed between January
      and December 1992 43 patients were enrolled and limb salvage was performed in 39
      of them (91%). The histologic response to chemotherapy was good (90% or more
      tumor necrosis) in 24 patients (56%) and poor (less than 90% tumor necrosis) in
      19 (44%). With a minimum follow-up of 7 years, 23 pts (53%) remained continuously
      free of disease, 19 relapsed and one died due to unrelated cause. In spite of the
      high number of limb salvages performed, only 2 local recurrences were registered.
      The 7-year event-free survival and overall survival were, respectively, 53% and
      68%. The hematopoietic and extrahematopoietic toxicity experienced by the
      patients during the entire treatment was relatively mild. These long-term results
      confirm that, with neoadjuvant chemotherapy, it is possible to cure more than 60%
      of patients with osteosarcoma of the extremities, avoiding amputation in most of
      them. These results, however, are no better than those achieved in our previous
      study IOR/OS-3a, in which only poor responder patients received ifosfamide during
      the postoperative treatment.

PMID- 11233809
TI  - A strategy for the development and standardisation of measurement methods for
      high power/cavitating ultrasonic fields: review of high power field measurement
      techniques.
AB  - This review was compiled as part of a project to formulate a UK strategy for the
      development and standardisation of measurement methods for high power/cavitating
      ultrasonic fields. It reviews the scientific literature relating to various
      methods of measuring high power fields which have been developed for application
      in health care, sonochemistry and industrial ultrasonics, and compares these
      methods in terms of attributes such as spatial resolution, bandwidth and
      sensitivity.

PMID- 11233810
TI  - Sonochemical reactions at 640 kHz using an efficient reactor. Oxidation of
      potassium iodide.
AB  - Ultrasound can be used to oxidize aqueous pollutants. However, due to economic
      reasons higher oxidation/destruction rates and higher energy efficiency are
      needed. Recent studies suggest that the higher ultrasound frequencies provide
      better oxidation rates than the conventional 20 kHz. Another area for improvement
      is reactor configuration. We have tested two new reactor configurations with
      proper focusing and reflection of ultrasound for maximum utilization. Reactor
      configuration plays an important role in the overall efficiency. In the new
      reactors, transducers and reaction mixture are separated by a polymer acoustic
      window which allows efficient transfer of ultrasound energy and not the heat from
      the transducer to the reaction mixture. One reactor at 640 kHz provides a 100%
      enhancement over the best reported rate for the oxidation of potassium iodide, on
      a per-Watt basis. Experiments conducted at varying initial KI concentrations show
      interesting behavior. Increasing the KI concentration by over eight fold merely
      increases the iodine production rate by two fold. This suggests that in the
      oxidation region surrounding the bubble, the KI concentration is much different
      than in the bulk. It is proposed that the hydrophobic bubble region has lower and
      near saturation KI concentration.

PMID- 11233811
TI  - Ultrasonic waste-water treatment: incidence of ultrasonic frequency on the rate
      of phenol and carbon tetrachloride degradation.
AB  - Organic compounds in aqueous solution submitted to an ultrasonic irradiation
      behave differently according to their physical and chemical properties. In this
      work, hydrogen peroxide formation and the degradation rate of phenol and carbon
      tetrachloride have been studied at different frequencies: 20, 200, 500 and 800
      kHz. Whatever the frequency, it is easier to decompose CCl4 than phenol by means
      of ultrasonic wave. It is shown that the rates of reactions involving hydroxyl
      radicals (hydrogen peroxide formation and phenol degradation) have a maximum
      value at 200 kHz. The best yield observed at 200 kHz for the phenol degradation
      may be the result of better HO radicals availability outside of the bubble of
      cavitation. The degradation rate for carbon tetrachloride which decomposes into
      the bubble of cavitation increases with frequency. Calculating the reaction rate
      for one ultrasonic period shows that the efficiency of one ultrasonic cycle
      decreases as frequency increases.

PMID- 11233812
TI  - Sonochemical enantioselective hydrogenation of ethyl pyruvate over platinum
      catalysts.
AB  - Chiral sonochemical hydrogenation of an aliphatic alpha-ketoester, ethyl pyruvate
      to ethyl lactate was carried out over various platinum catalysts in different
      solvents under atmospheric hydrogen pressure. The reaction rates and the
      enantiomeric excesses were determined over Pt/C, Pt/SiO2 and Pt/K-10 catalysts
      both under conventional and sonochemical conditions. The effect of ultrasounds on
      the catalytic activity and enantioselectivity was tested applying sonochemical
      pretreatment before the reaction. The ultrasonic irradiation was found to be
      highly advantageous in these hydrogenations. After insonation of the catalysts,
      the enantioselectivity was highly improved over Pt/SiO2 and Pt/K-10 catalysts. In
      addition, the reactions took place in quantitative yield and with complete
      chemoselectivity and the hydrogenation rates increased with one order of
      magnitude despite the very mild (atmospheric hydrogen pressure, room temperature)
      experimental conditions.

PMID- 11233813
TI  - The effect of ultrasound on the structure and properties of the water-soluble
      corn hull heteroxylan.
AB  - Ultrasonic irradiation of a water-soluble corn hull xylan fraction in neutral and
      alkaline aqueous medium has been found to produce significant changes in its
      molecular properties. Degradation is first manifested by a decrease in the large
      molar mass component under generation of polymer chains with about the same size
      as those of the main molar mass component. The latter is slightly shifted to the
      lower molar mass region only at stronger irradiation conditions. Ultrasonication
      of the xylan in neutral aqueous medium at high ultrasound power and/or long
      irradiation caused no significant changes in its sugar composition, primary
      structure and viscoelastic properties.

PMID- 11233814
TI  - Effect of ultrasound on the immunogenic corn cob xylan.
AB  - Changes in the structural, molecular and functional properties of the immunogenic
      corn cob xylan evoked by ultrasonication in water, 1% NaOH and 5% NaOH were
      investigated. The reduction of the high molar mass (MM) fraction was more intense
      than that of the medium MM fraction, depending on the sonic power, sonication
      time, and alkali concentration. The chain degradation was more effective in the
      alkaline media. The UV-absorbing component, accompanying the xylan polymers in
      the whole MM range, showed an accumulation in the high MM region as well as
      shiftening to higher sizes, particularly in 5% NaOH. The sugar composition and
      primary structure of the xylan was almost retained under all irradiation
      conditions studied. Although the biological activity of the xylan was affected by
      the ultrasound, no significant decrease of the biological response was found at
      short irradiation time and low sonic power.

PMID- 11233815
TI  - Preparation of Pd/C catalysts via ultrasound: a study of the metal distribution.
AB  - Palladium supported on active carbon catalysts was prepared using ultrasound
      during one of the preparation steps. An investigation of the metal distribution
      into the pores of the support was performed both by a deep characterization of
      the prepared samples and by a catalytic reaction involving some organic reactants
      to be reduced.

PMID- 11233816
TI  - Structural changes induced by ultrasound during aging of the boehmite phase.
AB  - Structural changes induced by ultrasound during the aging of the aluminum
      monohydroxide (boehmite) were studied by means of X-ray diffraction (XRD) and
      nitrogen adsorption. The BET surface area and the pore volume of the ultrasound
      stimulated hydroxide (HU) are about 40% less than those of the non-stimulated one
      (HS). The mean pore size practically does not change, while the mean crystallite
      size (L) is about 25% greater in the HU system. The increase of L alone is not
      enough to account for the surface area diminution, suggesting that the sonication
      also induces compaction by elimination of some porosity. The sonication of the
      precursor hydroxide does not seem to play an apparent role in the structural
      properties of the resulting calcinated gamma-alumina.

PMID- 11233817
TI  - Formation and inhibition of chloroaromatic micropollutants formed in incineration
      processes.
AB  - The formation pathways for chlorinated aliphatic and chlorinated aromatic
      compounds in technical incineration processes are reviewed. It is shown that
      acetylene is converted to chloroaromatic compounds including PCDD/F in a special
      flow reactor by catalytic activity of CuCl2 in the temperature regime of a post
      combustion zone of technical incinerators. Mechanistic pathways begin with
      chlorination of acetylene. Dichloroacetylene is further condensed to C-4 and C-6
      units. Hexachlorobenzene is the dominant aromatic compound and a likely precursor
      to chlorinated phenols and PCDD/F. Two specific mechanisms of formation of
      chlorinated aromatic compounds including PCDD/F have been advanced. Both
      mechanisms begin with the formation of dichloroacetylene from flame pyrolysis
      products like acetylene. Condensation of dichloroacetylene is mediated by copper
      species via metallacyclic intermediates and/or a catalytic cycle involving copper
      stabilized trichlorovinyl radicals. The final pathways of conversion of
      chlorinated benzenes to PCDD/F via chlorophenols are under active investigation.

PMID- 11233818
TI  - Dimethylcarbonate for eco-friendly methylation reactions.
AB  - Dimethylcarbonate (DMC), an environmentally friendly substitute for
      dimethylsulfate and methyl halides in methylation reactions, is a very selective
      reagent. Both under gas-liquid phase transfer catalysis (GL-PTC) and under batch
      conditions, with potassium carbonate as the catalyst, the reactions of DMC with
      methylene-active compounds (arylacetonitriles and arylacetoesters,
      aroxyacetonitriles and methyl aroxyacetates, benzylaryl- and alkylarylsulphones)
      produce monomethylated derivatives, with a selectivity not previously observed
      (i.e., >99%). The highly selective O-methylation of phenols and p-cresols by DMC
      is also attained by a new methodology using a continuous fed stirred tank reactor
      (CSTR) filled with a catalytic bed of polyethyleneglycol (PEG) and potassium
      carbonate.

PMID- 11233819
TI  - Advances with supercritical fluids.
AB  - In the last decade, supercritical fluids more and more have been proved as
      environmentally benign media for chemical and related processes. Many new
      processes and products have been developed, using the inherent physical and
      chemical properties of supercritical fluids. Moreover, these processes also
      promise economic effects. The prerequisites for this success however, are a sound
      knowledge of physico-chemical properties of--and phenomena in--supercritical
      mixtures and the availability of other chemical engineering data. This requires
      an effective exchange of knowledge between a large number of branches of science.
      In the following, a lot of recent papers will be cited, which should give an
      overview of actual results on fundamentals and their applications.

PMID- 11233820
TI  - Chemical industry reduces emissions--from production to the consumer.
AB  - Responsible care has always been an important issue at a chemical industry like
      Bayer. In recent years, the company has made extensive efforts to further improve
      its products and processes with regard to environmental protection and safety. In
      this contribution, a number of examples will highlight recent achievements of
      Bayer in the field of low or no emission processes and products. Examples are
      given in the fields of production-integrated environmental protection measures
      (new and improved processes e.g., for the production of adipic acid), the
      application of integrated environmental protection measures (2K-PUR water-borne
      coatings for cars) and product-integrated environmental protection measures
      (targeted application of insecticides/Attract and Kill) as a new low emission
      method to control insect pests.

PMID- 11233821
TI  - Base-catalyzed amination of olefins: an example of an environmentally friendly
      synthesis of amines.
AB  - The base-catalyzed amination of aromatic olefins is described as an
      environmentally friendly synthesis of various beta-arylethylamines. Primary and
      secondary aliphatic amines as well as aromatic amines react with styrene
      derivatives to give the corresponding beta-arylethylamines in high yield up to
      99%. While aliphatic amines react with styrenes in the presence of n-BuLi as the
      pre-catalyst, anilines can be olefinated using KOtBu as the catalyst.

PMID- 11233822
TI  - The fermentative production of L-lysine as an animal feed additive.
AB  - A new and innovative process for the biotechnological production of L-lysine is
      presented, exemplified here by the fermentative production of the feed additive
      Biolys60. The novel feature of this product is that the entire manufacturing
      concept, i.e. the production strain, the raw materials, all process stages and
      the product specifications have been systematically tailored for optimal
      environmental compatibility and for minimum resource depletion and waste. The
      process completely dispenses with the need to discharge residual and waste
      material and reduces the handling of hazardous materials to a minimum. Since only
      a few process stages are involved, the method is economical to use and investment
      outlay is reduced. The process, which also leads to a higher grade product, is
      thus highly attractive in both ecological and economical terms. By boosting the
      nutrient value of the plant-based feedstuffs, the product itself makes an cost
      effective contribution towards a more sustainable form of animal feeding and by
      reducing nitrogen emission levels promotes a more environmentally compatible form
      of animal husbandry.

PMID- 11233823
TI  - Environmentally compatible polymerization of olefins by the use of metallocene
      catalysts.
AB  - Polyolefins belong to the most non-polluting mass polymers since they consist of
      carbon and hydrogen, only. Additionally the pure polymers can be easily reused,
      they can be decomposed into their monomer building blocks or they can be burned
      to carbon dioxide and water under production of energy. With metallocene
      catalysts the efficiency of the polymerization compared to the common "Ziegler
      Natta" catalysts can be increased by the factor of 10-100. Therefore, resources
      are saved and energy costs decreased. The metallocene catalysts allow in a so far
      unknown fashion the synthesis of polymers in a very distinctive way. By variation
      of the ligand structure it is possible to influence as well the microstructure of
      the polymers as the stereo- and regio-selectivity and the tacticity in a broad
      range. Therefore, the production of polymers with outstanding mechanical
      properties becomes possible, so far these were reserved for high-performance
      polymers, which can be only made with high efforts and less environmentally
      compatible.

PMID- 11233824
TI  - Syntheses and application of polylactides.
AB  - Polylactides can be prepared by direct polycondensation of lactic acid, or
      better, by ring-opening polymerization of cyclic dilactides (usually called
      lactides). These lactides exist in the form of four stereoisomers two of which
      (L,L- and rac. -D,L-) are technically produced in large quantities. These
      lactides can by polymerized via four different classes of initiators and reaction
      mechanisms. The characteristics mechanistic and preparative features of the
      cationic polymerization, anionic polymerization and of the coordination-insertion
      mechanism are described. Furthermore, copolymerizations of lactides with
      glycolide or epsilon-caprolactone and their analytical problems are discussed.
      Finally, a new type of wound dressing based on transparent are resorbable films
      of copolylactides is mentioned.

PMID- 11233826
TI  - Waste-free solid-state syntheses with quantitative yield.
AB  - Unexpected organic solid-state reactions in the gas-solid and stoichiometric
      solid-solid versions are highly promising new tools for solvent-free sustainable
      synthesis and production if they occur with 100% yield. Costly workup is
      obsolete, no wastes are formed and resources and energy saved. More than 500
      published 100%-yield, solid-state reactions in 25 reaction types cover virtually
      all fields of synthetic organic chemistry. Atomic force microscopy (AFM) reveals
      that solid-state reactions require long-range molecular movements and are
      strictly and sensibly guided by the crystal packing. Three steps govern the
      issue: phase rebuilding, phase transformation, and crystal disintegration
      (detachment). If one of these fails, or if liquid phases are not avoided, the
      reaction will usually not run to completion. Repeated creation of fresh contacts
      of crystallites is essential in solid-solid reactions. New, otherwise
      inaccessible and highly reactive products are most easily obtained. Cooling below
      eutectic temperatures, but also thermal activation above room temperature, may be
      necessary. Liquids may be solidified by cooling or inclusion complexation.
      Typical single-step, multi-step and cascade reactions have been performed with
      100% yield using commonly available starting materials in various fields.
      Upscaling to the kilogram scale has been achieved under various conditions.
      Further upscaling to technical size productions seems possible.

PMID- 11233825
TI  - Introducing integrated product and process development into the education of
      science and engineering undergraduates: a lecture course with an accompanying
      case-study programme at the ETH chemistry department.
AB  - Increased quality requirements in the development of chemical products and a
      growing awareness within society of the activities of chemical companies present
      a new challenge to the education of young scientists. Nowadays, the teaching of
      chemists, chemical engineers and environmental scientists at universities has to
      go beyond the traditional, discipline-orientated knowledge acquisition. The
      students also have to learn to work and communicate in interdisciplinary teams,
      to solve application-oriented tasks and to integrate scientific, economical,
      ecological and social aspects into their work. For this reason, a case-study
      programme was launched at the chemistry department of the Swiss Federal Institute
      of Technology. In this paper, we describe the organisational aspects of the
      programme, its inclusion into academic and industrial environments and summarise
      some of the scientific methodologies applied. One of the seven case-studies, an
      assessment of a modern insecticide, is presented in more detail. Finally, we
      discuss how far the case-study programme is suitable for introducing a new mode
      of knowledge production to universities.

PMID- 11233827
TI  - Environmental protection and economization of resources by electroorganic and
      electroenzymatic syntheses.
AB  - The electrochemical methodology is an intrinsically environmentally friendly
      technique. It is especially excellently suited for preventive environmental
      protection because the practically mass-free electrons are used as reagents.
      Therefore, it allows the production of organic compounds without the formation of
      ecologically critical waste which has to be disposed. In addition, toxic waste
      formation can be prevented by continuous in situ or two-step electrochemical
      regeneration of heavy metal redox reagents. By using solid polymer electrolytes
      (ion-exchange membranes), even the use of a supporting electrolyte can be
      avoided. Thus, product formation can take place in pure methanol without any
      other chemical present. The consumption of resources can be economized by
      generating high-value products on both electrodes, anode and cathode (paired
      electrosynthesis). In certain cases, the same product may be formed on the anode
      and the cathode (200%-cell). Finally, in electroenzymatic syntheses, two
      environmentally friendly methods can be combined for the regeneration of the
      cofactors or the prosthetic groups of redox enzymes.

PMID- 11233828
TI  - Formation of 1,1'-iminodicarboxylic acid derivatives, 2,6-diketo-piperazine and
      dibenzodiazocine-2,6-dione by variations of multicomponent reactions.
AB  - The combination of multicomponent reactions (MCRs) of different amino acids,
      aldehydes, isocyanides and acids allows complex structures to be prepared in one
      pot reactions. The synthesis of 1,1'-iminodicarboxylic acid derivatives 12
      demonstrates the high selectivity of the Ugi Four Component Reaction using two
      different aldehydes and two different isocyanides. The limitations of the MCRs
      are illustrated by the synthesis of a 1,1'-iminodicarboxylic acid derivative 6
      from L-lysine. Furthermore, 2,6-diketopiperazines and dibenzodiazocin-2,6-diones
      are synthesized via MCRs.

PMID- 11233829
TI  - Organic reactions without organic solvents and oils and fats as renewable raw
      materials for the chemical industry.
AB  - The use of organic solvents should be minimized as far as possible to reduce
      atmospheric volatile organic compounds (VOCs). Examples of solvent-free organic
      syntheses are described. The increasing usage of renewable feedstocks taking
      advantage of the synthetic potential of nature is another way to avoid organic
      solvents. Most important is the development of chemical products, i.e., coatings
      that can be processed without organic solvents.

PMID- 11233830
TI  - Lubricants based on renewable resources--an environmentally compatible
      alternative to mineral oil products.
AB  - The development of lubricants like, e.g. engine and hydraulic oils was
      traditionally based on mineral oil as a base fluid. This fact is related to the
      good technical properties and the reasonable price of mineral oils. The Report to
      the Club of Rome (W.W. Behrens III, D.H. Meadows, D.I. Meadows, J. Randers, The
      limits of growth, A Report to the Club of Rome, 1972) and the two oil crises of
      1979 and 1983, however, elucidated that mineral oil is on principle a limited
      resource. In addition, environmental problems associated with the production and
      use of chemicals and the limited capacity of nature to tolerate pollution became
      obvious (G.H. Brundtland, et al., in: Hauff, Volker (Ed.), World Commission on
      Environment and Development (WCED), Report of the Brundtland-Commission, Oxford,
      UK, 1987), and the critical discussion included besides acid rain, smog, heavy
      metals, and pesticides also mineral oil (especially oil spills like the case
      Exxon Valdes). A disadvantage of mineral oil is its poor biodegradability and
      thus its potential for long-term pollution of the environment. From the early
      development of lubricants for special applications (e.g. turbojet engine oils) it
      was known, that fatty acid polyol esters have comparable or even better technical
      properties than mineral oil. Subsequently, innumerable synthetic esters have been
      synthesized by systematic variation of the fatty acid and the alcohol components.
      Whereas the alcohol moiety of the synthetic esters are usually of petrochemical
      origin, the fatty acids are almost exclusively based on renewable resources. The
      physico-chemical properties of oleochemical esters can cover the complete
      spectrum of technical requirements for the development of high-performance
      industrial oils and lubricants (e.g. excellent lubricating properties, good heat
      stability, high viscosity index, low volatility and superior shear stability).
      For a comprehensive review of their technical properties see F. Bongardt, in:
      Jahrbuchfur Praktiker, H. Ziolkowsky (Ed.), Verlag fur chemische Industrie GmbH,
      1996, pp. 348-361. This article will focus on the ecological properties of
      oleochemical (synthetic) esters. The environmental relevance of oleochemicals in
      comparison to petrochemicals is discussed, and then the principles of an
      ecological assessment are described. The ecotoxicological properties and the
      biodegradability of oleochemical esters are presented. Finally, the ecological
      properties of the oleochemical esters are discussed with regard to existing
      environmental classification and labeling systems.

PMID- 11233831
TI  - Development of an environmentally benign process for the production of fatty acid
      methyl esters.
AB  - The production of fatty acid methyl esters (FAME) is an important intermediate
      step in oleochemistry. The oleochemical production route starts with the
      renewable raw materials fat and oil and ends at fatty alcohols and different
      special products. Fatty acid methyl esters can be formed at mild reaction
      temperatures by transesterification of natural triglycerides (fats and oils).
      This contribution will show the development of a continuous process which is
      considering the main principles of production integrated environmental
      protection. The main advantages of this process are low energy consumption and
      minimal waste production. The process alternatives are shown and a scope on
      future problems which have to be solved to reach a real additional improvement of
      the fatty acid methyl esters production is given.

PMID- 11233833
TI  - [Is there a benefit of postoperative pelvic irradiation in patients with FIGO
      stage I endometrial carcinoma?].

PMID- 11233832
TI  - Clinical indications and biological mechanisms of splenic irradiation in
      autoimmune diseases.
AB  - BACKGROUND: Splenic irradiation (SI) is a fairly unknown treatment modality in
      autoimmune disorders like autoimmune thrombocytopenia (AIT) or autoimmune
      hemolytic anemia (AIHA), which may provide an effective, low toxic and cost
      effective treatment for selected patients. PATIENTS, MATERIALS AND METHODS: This
      article reviews the limited experiences on splenic irradiation in autoimmune
      thrombocytopenia by analyzing the current studies including 71 patients and some
      preliminary reports on splenic irradiation in autoimmune hemolytic anemia.
      RESULTS: In autoimmune thrombocytopenia between 40 and 90% of all patients
      responded, but most of them relapsed within 4 to 6 months after splenic
      irradiation. Between 10 and 20% of all patients had a sustained response. The
      efficacy of splenic irradiation in HIV-associated cases of thrombocytopenia is
      probably lower than in other forms of autoimmune thrombocytopenia, but especially
      in this group immunosuppressive drug treatment of autoimmune thrombocytopenia
      exposes some problems. In autoimmune hemolytic anemia there are some case reports
      about efficacy of splenic irradiation. Toxicity of splenic irradiation in both
      diseases was very moderate. CONCLUSIONS: For HIV patients, for elderly patients
      or patients at high risk for complications following splenectomy splenic
      irradiation might be a treatment option. Splenic irradiation as preoperative
      treatment in patients not responding to or not suitable for immunosuppressive
      drugs prior to splenectomy may be a promising new application of splenic
      irradiation to reduce adverse effects of splenectomy in thrombocytopenic
      patients. A further analysis of the biological mechanisms underlying splenic
      irradiation may help to improve patient selection, to optimize dose concepts and
      treatment schedules and will improve understanding of radiotherapy as an
      immunomodulatory treatment modality.

PMID- 11233834
TI  - [Intra-arterial preoperative chemotherapy versus preoperative radiotherapy].

PMID- 11233835
TI  - [Meta-analysis of the value of cisplatin in primary therapy of small-cell
      bronchial carcinoma].

PMID- 11233836
TI  - [Incidence of tumors after treatment with oral anticoagulants].

PMID- 11233838
TI  - [Optimization of radiotherapy in Dupuytren's disease. Initial results of a
      controlled trial].
AB  - PURPOSE: Radiotherapy prevents progression of Dupuytren's contracture. Herein, 1
      year results of a prospective randomized trial comparing 2 different dose
      concepts are presented. PATIENTS AND METHODS: 129 patients (67 males, 62 females)
      were included in the study with a minimum 1-year follow-up: 69 had bilateral and
      60 unilateral involvement of Dupyutren's disease accounting for 198 irradiated
      hands. According to Tubiana, 73 hands had Stage N, 61 Stage N/I (< or = 10
      degrees flexion deformity), 59 Stage I (11 to 45 degrees) and 5 Stage II disease
      (46 to 90 degrees). Radiotherapy was randomly delivered: group A (63 patients/95
      hands) received 10 times 3 Gy (total: 30 Gy) in 2 series (each 5 times 3 Gy)
      separated by 8 weeks; group B (66 patients/103 hands) received 7 times 3 Gy
      (total: 21 Gy) within 2 weeks. Orthovoltage radiotherapy (120 kV) with 40 cm
      standard cones and individual shielding was applied. Patient and disease
      parameters were equally distributed in both groups. Evaluation (toxicity,
      efficacy) was performed at 3 and 12 months with regard to subjective (patient's
      opinion) and objective parameters (palpation, measurements, comparative
      photographs--physician). RESULTS: Acute toxicity was minimal: 76 (38%) hands had
      skin reactions CTC Grade 1, 12 (6%) CTC Grade 2. Chronic side effects (dryness,
      skin atrophy, change of sensation, LENT Grade 1) occurred in 9 (5%) hands without
      differences between treatment groups. At 3 and 12 months follow-up, subjective
      symptoms and objective signs, nodules and cords, were reduced in both groups (p <
      0.01) with no differences between groups: a total of 110 (55%) hands (group A:
      55, group B: 55) regressed, 74 (37%) hands (group A: 35; group B: 39) were
      stable. Overall and mean number of nodules, cords and skin changes decreased at 3
      and 12 months. 16 of 198 (8%) hands (group A: 7; group B: 9) progressed at 12
      months follow-up ("treatment failure"); at 1 year, 7 of 60 patients with
      unilateral Dupyutren's disease required prophylactic radiotherapy for the
      contralateral hand due to disease progression. CONCLUSIONS: Prophylactic
      radiotherapy reduces symptoms and prevents disease progression in early-stage
      Dupyutren's disease. Both treatment concepts are well-tolerated and equally
      effective. Acute toxicity is slightly increased with treatment concept B (7 times
      3 Gy), while chronic sequelae are low in both treatment groups. Long-term
      evaluation with follow-up of more than 5 years has to be awaited to recommend one
      or the other dose concept.

PMID- 11233837
TI  - Aspects of MR image distortions in radiotherapy treatment planning.
AB  - BACKGROUND: Registration of computed tomography (CT) and magnetic resonance (MR)
      images are commonly performed to define the different target regions used in
      radiotherapy treatment planning (RTTP). The accuracy of target definition will
      then depend on the spatial accuracy of the CT and MR data, and on the technique
      used to register the images. CT images are usually regarded as geometrically
      correct, while MR images are known to suffer from geometric distortion. The aim
      of this paper is to discuss the possible impact of MR image distortions in the
      radiotherapy treatment planning process. METHODS: The origin, magnitude, and
      relative impact of the different sources of geometric distortions that affect the
      MR image data at different magnetic fields and for different acquisition settings
      are described. Techniques for distortion correction are reviewed, and their
      limitations are outlined. The sensitivity of image registration techniques to the
      presence of geometric distortions in the MR data is discussed. Finally, an
      overview of image registration techniques used and results obtained in clinical
      radiotherapy treatment planning applications is given. RESULTS: Spatial
      distortions in MR images vary with field strength and with the image acquisition
      protocol. The spatial accuracy generally decreases with distance from the magnet
      isocenter. Distortion correction techniques based on phantom evaluations cannot
      adequately model patient-induced distortions. CONCLUSION: Image protocols with
      high gradient bandwidths should be used to reduce the spatial distortions in MR
      images. Correction techniques based only on phantom measurements could be
      sufficient at low magnetic fields, while at higher fields additional corrections
      of patient-related distortions might be needed. Registration techniques based on
      matching of Landmark points located far from the magnet isocenter are especially
      prone to MR distortions.

PMID- 11233839
TI  - Radiotherapy is an effective treatment for high-risk T1-bladder cancer.
AB  - PURPOSE: Current treatment options for high-risk superficial T1-bladder cancer
      (Grade 3, associated Tis, multifocality, tumor diameter > 5 cm or multiple
      recurrences) include early cystectomy or the goal of organ preservation by
      adjuvant intravesical therapy after transurethral resection (TURB). We have
      evaluated the efficacy of adjuvant radiotherapy or radiochemotherapy on local
      control, bladder preservation, recurrence rate and long-term survival after TURB
      of high-risk T1-bladder cancer. PATIENTS AND METHODS: From May 1982 to May 1999,
      a total of 74 patients with T1-bladder cancer were treated by either radiotherapy
      (n = 17) or concomitant radiochemotherapy (n = 57) after TURB. Radiotherapy was
      initiated 4 to 8 weeks after TURB; a median dose of 54 (range: 45 to 60) Gy was
      applied to the bladder with daily fractions of 1.8 to 2.0 Gy. Since 1985
      chemotherapy has been given in the 1st and 5th week of radiotherapy and consisted
      of cisplatin (25 mg/m2/d) in 33 patients, carboplatin (65 mg/m2/d) was
      administered in 14 patients with decreased creatine clearance (< 50 ml/min).
      Since 1993 a combination of cisplatin (20 mg/m2/d) and 5-fluorouracil (600
      mg/m2/d) was applied to 10 patients. Salvage cystectomy was recommended for
      patients with refractory disease or invasive recurrences. At the time of
      analysis, the median follow-up for surviving patients was 57 (range: 3 to 174)
      months. RESULTS: After radiotherapy/radiochemotherapy, a complete remission at
      restaging TURB was achieved in 62 patients (83.7%), 35 of whom (47% with regard
      to the total cohort of the 74 treated patients) have been continuously free of
      tumor, 11 patients (18%) experienced a superficial relapse and 16 patients (26%)
      showed tumor progression after initial complete response. Overall-survival was
      72% at 5 years and 50% at 10 years with 77% of the surviving patients maintaining
      their own bladder at 5 years. Negative prognostic factors for cancer-specific
      survival were non-complete (R1/2) initial TURB (p = 0.12) and recurrent disease
      (p = 0.07); combined radiochemotherapy was more effective than radiotherapy alone
      (p = 0.1). CONCLUSION: Adjuvant radiotherapy/radiochemotherapy offers an
      additional option in high-risk superficial bladder cancer with a high chance of
      cure and bladder preservation. The ultimate value of radiotherapy in comparison
      with other treatment options should be determined in randomized trials.

PMID- 11233840
TI  - PSA kinetics after external beam radiotherapy alone or combined with an iridium
      brachytherapy boost to deliver 85 grays to prostatic adenocarcinoma.
AB  - PURPOSE: Increasing the dose to prostatic adenocarcinoma in conformal external
      beam therapy (EBT) has resulted in increased levels of PSA normalization and
      increased percentage of biochemical disease-free survival rates. However
      technical problems due to prostate motion inside the pelvis or patients' set-up
      make difficult the realization of the EBT boost fields above 72 Gy. Brachytherapy
      which overcomes these problems was investigated to deliver the boost dose to
      achieve 85 Gy. PSA nadir which has been identified as the strongest independent
      predictor of any failure in many studies has been used as the end point for early
      evaluation of this work. PATIENTS AND METHODS: In a retrospective way we report
      on 163 patients' PSA kinetics after EBT alone to 68 Gy or EBT first and a
      brachytherapy boost up to 75 or 85 Gy. RESULTS: At 12 months follow-up, PSA
      nadirs percentage < or = 0.5 or < or = 1 ng/ml increased from 7.5 and 20.7% after
      68 Gy EBT to 49.8 and 71.2% after a brachytherapy boost to deliver 85 Gy (p <
      0.0001). In the Cox PH model analysis, the total dose remained the most important
      factor for predicting PSA normalization. CONCLUSIONS: These results are in
      accordance with the most recent results published after conformal EBT at the same
      80 Gy level of dose. If confirmed on a higher number of patients they could place
      brachytherapy among the most accurate methods of boosting in the radiation
      treatment of prostatic carcinoma.

PMID- 11233841
TI  - [Chronic radiation effects on dental hard tissue (radiation caries).
      Classification and therapeutic strategies].
AB  - OBJECTIVES: Since the first description of rapid destruction of dental hard
      tissues following head and neck radiotherapy 80 years ago, "radiation caries" is
      an established clinical finding. The internationally accepted clinical evaluation
      score RTOG/EORTC however is lacking a classification of this frequent radiogenic
      alteration. MATERIAL AND METHODS: Medical records, data and images of radiation
      effects on the teeth of more than 1,500 patients, who underwent
      periradiotherapeutic care, were analyzed. Macroscopic alterations regarding the
      grade of late lesions of tooth crowns were used for a classification into 4
      grades according to the RTOG/EORTC guidelines. RESULTS: No early radiation
      effects were found by macroscopic inspection. In the first 90 days following
      radiotherapy 1/3 of the patients complained of reversible hypersensitivity, which
      may be related to a temporary hyperemia of the pulp. It was possible to classify
      radiation caries as a late radiation effect on a graded scale as known from
      RTOG/EORTC for other organ systems. This is a prerequisite for the integration of
      radiation caries into the international nomenclature of the RTOG/EORTC
      classification. CONCLUSIONS: The documentation of early radiation effects on
      dental hard tissues seems to be neglectable. On the other hand the documentation
      of Late radiation effects has a high clinical impact. The identification of an
      initial lesion at the high-risk areas of the neck and incisal part of the tooth
      can lead to a successful therapy as a major prerequisite for orofacial
      rehabilitation. An internationally standardized documentation is a basis for the
      evaluation of the side effects of radiooncotic therapy as well as the
      effectiveness of protective and supportive procedures.

PMID- 11233842
TI  - DNA metabolism in mycobacterium tuberculosis: implications for drug resistance
      and strain variability.
AB  - In this paper, we review the evidence supporting the notion that the genome of
      Mycobacterium tuberculosis sustains considerable damage as a result of exposure
      to nitrosative and oxidative stress. On these grounds, we propose a model in
      which stress-induced DNA damage in M. tuberculosis plays a role in the evolution
      of chromosomally encoded drug resistance mutations by altering the global
      mutation rate by mechanisms akin to SOS mutagenesis. Finally we review some of
      the factors determining the evolution of PE/PPE and MIRU (There are many
      abbreviations in this paper which are not defined, e.g. SOS, PE/PPE and MIRU.
      Please indicate whether these are well known and will be understood by readers or
      whether they should be defined at first mention) loci whose sequence
      characteristics are suggestive of their classification as heritable local
      mutators.

PMID- 11233843
TI  - High levels of mRNA encoding IL-4 in unstimulated peripheral blood mononuclear
      cells from tuberculosis patients revealed by quantitative nested reverse
      transcriptase-polymerase chain reaction; correlations with serum IgE levels.
AB  - The dominant view has been that there is little or no activation of Type 2
      cytokine production in human tuberculosis. A novel approach to quantitative
      nested reverse transcriptase-polymerase chain reaction has revealed that this
      conclusion was based on technical inadequacies of earlier studies, particularly
      the failure to discriminate between IL-4 and the IL-4 splice variant, IL4delta2.
      A new approach reveals that the largest cytokine change in tuberculosis is a 1-2
      log increase in copy number for mRNAs encoding IL-4 and IL-13, accompanied by a
      small decrease in expression of mRNA encoding interferon-gamma. The increased IL
      4 level correlates with disease severity and with serum levels of IgE and soluble
      CD30, and may be attributable to the recently observed increase in conversion of
      cortisone into cortisol in tuberculous lesions. The implications of these
      findings for pathogenesis, vaccine design and immunotherapy are discussed, as
      effective reagents will need to downregulate this inappropriate Th2 component.

PMID- 11233844
TI  - Monitoring virological responses to interferon-ribavirin and interferon
      monotherapy of chronic hepatitis C re-treated due to relapse or non-response.
AB  - Adding the nucleoside analog ribavirin (RBV) to interferon (IFN) for treatment of
      HCV has improved the sustained response rates, but the mechanism by which RBV
      mediates viral clearance is not fully understood. In this study, a highly
      sensitive method (Codes Amplicor HCV Monitor) was used to monitor the early
      (first 12 weeks of therapy) and long-term virological response in 20 patients who
      were treated first with IFN and later, due to non-sustained response, with IFN
      RBV. All 10 IFN relapsers displayed a prompt virological response at week 4 to
      both IFN and IFN-RBV therapy; nine of them showed a sustained response to IFN
      RBV. Out of 10 IFN non-responders, five showed a sustained response to IFN-RBV.
      Four of these were HCV RNA-negative at week 4 of IFN-RBV therapy and two of them
      had a transient early virological response (RNA-negative at weeks 4-8) to IFN
      alone. Overall, of the 14 patients (nine IFN relapsers, five IFN non-responders)
      with a sustained response to IFN-RBV, 11 and 13 had HCV RNA below 2000 copies/ml
      at week 4 of IFN and IFN-RBV, respectively, as compared with one and one of six
      patients without a sustained response to IFN-RBV (p < 0.02). Thus, addition of
      RBV to IFN increased both viral clearance during the first 12 weeks of therapy
      and the rate of sustained response. Loss of viremia at week 4 of IFN was
      associated with a sustained response to IFN-RBV and was seen in 11 of 13 patients
      (85%) with genotypes 2 or 3, as compared with one of seven patients (14%) with
      genotype 1 (p = 0.0044).

PMID- 11233845
TI  - Acute self-limiting hepatitis C after possible sexual exposure: sequence analysis
      of the E-2 region of the infected patient and sexual partner.
AB  - We describe a case of symptomatic acute infection with HCV in a woman whose
      sexual partner had chronic hepatitis C. The patient cleared HCV RNA 8 weeks after
      the onset of acute hepatitis and was found to be persistently HCV-RNA negative
      during 90 weeks of follow-up. Part of the E-2 region of HCV was directly
      sequenced in the patient and her sexual partner. Four local controls with subtype
      1a infection and 9 1a isolates obtained from GenBank were analyzed. The average
      nucleotide divergence between the sequences of the infected patient and her
      sexual partner was 5.1%, compared with an average nucleotide divergence of 19.4%
      (range 16.6-21.8%) between the sequences of the patient and those of controls.
      Comparison of the phylogenetic trees in the partial E-2 region showed that the
      sequence of the patient was closely related to that of her sexual partner. Our
      findings suggest that the infection was transmitted to the patient from her
      sexual partner. The resolution of acute hepatitis C in this case was probably
      related to the host rather than to intrinsic characteristics of the HCV genome.

PMID- 11233846
TI  - Infection with hepatitis A and TT viruses and socioeconomic status in Rio de
      Janeiro, Brazil.
AB  - The prevalence of antibodies directed against the enterically transmitted
      hepatitis A virus (HAV) was measured in 2 groups of people living in Rio de
      Janeiro, Brazil. Of 1,056 health care workers (HCWs), 778 (73.7%) were anti-HAV
      positive. A high prevalence of anti-HAV antibodies (85.7%) was also found among
      274 voluntary blood donors (BDs). TT virus (TTV) is a DNA virus that has been
      found in the sera of patients with post-transfusion hepatitis of unknown
      etiology. Occurrence of virus shedding suggests that the fecal-oral route may be
      an important mode of TTV transmission, particularly in the developing world. The
      presence of TTV DNA was analyzed by PCR in the sera of 191 HCWs and 151 BDs. TTV
      was detected in 65.4% of HCWs and 79.5% of BDs. In both groups, a family income
      of < US$400 per month and a level of education of < 11 y of schooling were found
      to be risk factors for HAV infection. Furthermore, a low family income was
      associated with TTV viremia in the HCW group. However, the presence of TTV DNA
      was associated with neither low level of education nor anti-HAV positivity.

PMID- 11233847
TI  - Campylobacter fetus subspecies fetus bacteremia associated with chorioamnionitis
      and intact fetal membranes.
AB  - Campylobacter fetus subspecies fetus was isolated from the blood of a patient
      with chorioamnionitis and intact fetal membranes. The mother improved after
      appropriate antibiotic treatment, but the infant died of neonatal infection a few
      minutes after delivery. This is a very unusual etiology of intra-amniotic
      infection.

PMID- 11233848
TI  - Borrelia burgdorferi antibodies in outdoor and indoor workers in south-west
      Sweden.
AB  - Two hundred and fifty-three farmers and forest workers and 249 clerks from south
      west Sweden were recruited to a cross-sectional seroprevalence study to find out
      if individuals working outdoors are more prone to acquire Borrelia burgdorferi
      infection than indoor workers and to find undiagnosed cases of Lyme borreliosis.
      The participants answered a questionnaire and blood specimens were collected to
      estimate the prevalence of antibodies to B. burgdorferi in each group. Sera were
      analysed with an enzyme-linked immunoassay technique to determine IgG antibodies
      to B. burgdorferi flagellum. The prevalence of B. burgdorferi antibodies was 7.6%
      in the farmers and forest workers vs. 5.3% in the clerks (adjusted odds ratio
      [age, sex] = 1.2 [95% confidence interval = 0.5-2.8]). One case of Lyme
      borreliosis was diagnosed. The positive predictive value of the antibody test was
      estimated to be 3% in the studied populations. B. burgdorferi infection is of low
      endemicity in south-west Sweden and is probably not an occupational risk among
      outdoor workers. Undiagnosed cases of Lyme borreliosis are uncommon. The test
      used is not acceptable for screening purposes.

PMID- 11233849
TI  - Demonstration of Chlamydia pneumoniae in the adenoid from children with and
      without secretory otitis media using immunohistochemistry and PCR.
AB  - Chlamydia pneumoniae has been found in patients with middle ear inflammation. The
      adenoid, which has a central role in the development of secretory otitis media
      (SOM), may act as a reservoir for bacteria causing ear infection. Adenoid tissue
      was examined for the presence of C. pneumoniae. Twenty children undergoing
      adenoidectomy because of hyperplastic adenoids, 10 with SOM and 10 without SOM,
      were examined with nasopharyngeal swabs for routine bacteriological culture,
      serology for C. pneumoniae and throat swabs for C. pneumoniae PCR. The removed
      tissues were analyzed for C. pneumoniae using immunohistochemical (IHC) analysis
      and PCR. In the group of children with SOM samples were also taken from the
      middle ear fluid for routine bacteriological culture and PCR for C. pneumoniae.
      C. pneumoniae was found in the adenoid by PCR in 3 cases from each group and from
      all 20 children by IHC. Four children in each group had increased levels of
      specific antibodies to C. pneumoniae. Two children with SOM had high antibody
      titers and a positive PCR from a throat swab. Two children were PCR-positive for
      C. pneumoniae in fluid from the middle ear. The significance of these findings is
      not yet clear.

PMID- 11233850
TI  - Candidemia before and during the fluconazole era: prevalence, type of species and
      approach to treatment in a tertiary care community hospital.
AB  - The characteristics of candidemia before and after the introduction of
      fluconazole were compared at our institution. In the pre-fluconazole era (1986
      89), the incidence of candidemia rose from 0.02% to 13% over the course of 4 y.
      Candida albicans accounted for 44/66 isolates (67%) and C. glabrata and C.
      parapsilosis were the predominant non-albicans species (9% each). In one-third of
      cases antifungal therapy was not given and the overall mortality rate was 55%.
      During the fluconazole era (1994-97), the incidence of candidemia remained
      constant between 1994 and 1996 at 0.09-0.11% and dropped to 0.06% in 1997.
      Bloodstream infection associated with neutropenia increased significantly but
      only accounted for 13% of cases; antifungal prophylaxis was not employed. The
      isolation of C. albicans decreased (n = 49; 50%) whereas isolation of both C.
      parapsilosis (n = 23; 24%) and C. tropicalis (n = 16; 16%) increased. The vast
      majority of patients received antifungal therapy and the overall mortality rate
      was 39%. These findings show that the incidence of candidemia rose steadily prior
      to the fluconazole era and then stabilized in spite of a shift towards non
      albicans species. When candidemia was encountered in the fluconazole era, it was
      rare not to give antifungal treatment.

PMID- 11233851
TI  - Epidemiological typing of Candida albicans from bloodstream infections by
      restriction enzyme analysis.
AB  - Candida albicans blood culture isolates (n = 142) from 130 patients treated in 7
      acute care hospitals in Southern Finland between 1986 and 1995 were typed by
      restriction enzyme analysis (REA) with EcoRI and MspI. REA revealed 118 distinct
      DNA types: 13 were detected in > 1 patient and 105 DNA types were unique.
      Patients with identical DNA types were not temporally or geographically
      clustered. Among 11 patients with more than 1 C. albicans isolate during 1
      episode of fungemia the DNA type remained the same, except in 1 patient. These
      results indicate that REA is a powerful tool for the epidemiological typing of C.
      albicans infections.

PMID- 11233852
TI  - Long-lasting recall response of CD4+ and CD8+ alphabeta T cells, but not
      gammadelta T cells, to heat shock proteins of francisella tularensis.
AB  - Decades after recovery from tularemia, circulating alphabeta T cells are known to
      still recognize a variety of membrane proteins of Francisella tularensis. We
      studied the T cell response to 3 cytoplasmic heat shock proteins of the organism:
      DnaK, chaperone-60 (Cpn-60) and Cpn-10. Determination of subpopulations of
      responding T cells was of special interest as it has been suggested that homologs
      of these conserved proteins may be recognized by human gammadelta T cells.
      Compared with reference subjects with no history of tularemia or tularemia
      vaccination, subjects who had been infected with tularemia 10-30 y earlier showed
      a significantly (p = 0.01) higher proliferative T cell response to all 3 heat
      shock proteins. In general, the magnitude of responses of CD4 T cells was higher
      than that of CD8 T cells. By flow cytometry, blast cells were shown to express
      the alphabeta T cell receptor. Under conditions that allowed vigorous expansion
      of gammadelta T cells in response to a phosphorylated non-peptide antigen, no
      expansion of gammadelta T cells occurred in response to DnaK or Cpn60 of F.
      tularensis. In conclusion, a long-lasting recall response to heat shock proteins
      of F. tularensis was demonstrated in alphabeta T cells but not in gammadelta T
      cells. The results support the assumption that human alphabeta T cells recognize
      bacterial proteins irrespective of the nature or localization of the proteins in
      the bacterial cell and thereby contribute to the maintenance of a long-lasting
      broad T cell response based on a wide variety of specificities.

PMID- 11233853
TI  - Subcutaneous myiasis caused by Dermatobia hominis.
AB  - A case of subcutaneous myiasis caused by the larvae of the Dermatobia hominis fly
      is described, involving the ankle region of a 25-y-old man who had returned from
      Peru. After removal of 4 larvae from the affected sites, the lesions healed in 2
      weeks without further treatment. Because of the increasing number of people
      travelling to tropical America, physicians in Slovenia will have to consider
      Dermatobia myiasis in the differential diagnosis of furuncular lesions in
      patients with a relevant travel history.

PMID- 11233854
TI  - A case of Moraxella canis-associated wound infection.
AB  - Moraxella canis was isolated from an infected foot ulcer in a patient suffering
      from diabetes mellitus with neuropathy. Bacteriological findings and 16S rDNA
      data are presented.

PMID- 11233855
TI  - Teicoplanin-induced neutropenia in a paediatric patient with vertebral
      osteomyelitis.
AB  - Teicoplanin is a glycopeptide antibiotic that has been used extensively in adults
      but less so in children for the treatment of bone and joint infections. It has a
      good safety profile with low incidences of blood dyscrasias. We report a case of
      teicoplanin-induced neutropenia in a child.

PMID- 11233856
TI  - Group A streptococcal brain abscess.

PMID- 11233857
TI  - Cellular HIV-1 immune responses in natural infection and after genetic
      immunization.
AB  - By eliminating infected cells, virus-specific cytotoxic T-lymphocytes (CTL) play
      a central role in host protection. Many studies to date seem to support the
      concept that human immunodeficiency virus (HIV)-specific CTL responses contribute
      to the control of viral replication, and thus delay the onset of disease. The
      feasibility of improving the virus-specific T-cell immunity by immunizing during
      the asymptomatic phase of infection has been studied in man. DNA vaccination is a
      novel strategy, involving direct inoculation of genetic material that is capable
      of producing antigen intracellularly for presentation to CTL. Such DNA-based
      immunization has been shown in animal models to be effective for the induction of
      both cellular and humoral immune responses as well as for protection from
      infectious challenge. This article reviews the cell-mediated immune responses in
      natural HIV-1 infection and the induction by DNA vaccination in humans.

PMID- 11233858
TI  - Activation of toll-like receptors by microbial lipoproteins.
AB  - In Drosophila, the Toll family of proteins are central to innate defense against
      microbial pathogens. Conserved throughout evolution, mammalian Toll-like
      receptors (TLRs) participate in innate immunity. TLRs mediate activation by
      microbial ligands including lipoproteins, resulting in the activation of IL-12
      and nitric oxide synthase. Microbial lipoproteins also induce host cell
      apoptosis. In this manner, the ability of microbial lipoproteins to activate TLRs
      can contribute to host defense and immunopathology during infection.

PMID- 11233859
TI  - Management of newly diagnosed patients with epilepsy: a systematic review of the
      literature.

PMID- 11233860
TI  - A ban on asbestos: is now the time?

PMID- 11233861
TI  - Narcotics for chronic nonmalignant pain.

PMID- 11233862
TI  - Thwarting sore throats.

PMID- 11233863
TI  - Thwarting sore throats.

PMID- 11233864
TI  - Remote versus urban medical training.

PMID- 11233865
TI  - Remote versus urban medical training.

PMID- 11233866
TI  - Preventive health care, 2001 update: screening mammography among women aged 40-49
      years at average risk of breast cancer.
AB  - OBJECTIVE: A previous review by the Canadian Task Force on the Periodic Health
      Examination (now the Canadian Task Force on Preventive Health Care) in 1994
      indicated fair evidence to exclude mammographic breast cancer screening of women
      aged 40-49 from the periodic health examination. This current review considers
      the available new and updated evidence regarding the effect of screening
      mammography on breast cancer mortality among women in this age group at average
      risk of breast cancer. OPTIONS: Screening mammography starting at either age 40
      or age 50. OUTCOME: Reduction in breast cancer mortality. EVIDENCE: The MEDLINE
      and CANCERLIT databases were searched for relevant articles published from 1966
      to January 2000. Of 68 references obtained, at least 22 were published after the
      1994 review. To date, the only trial designed to assess the mortality benefits of
      screening mammography among women aged 40-49 did not have adequate power to
      exclude a clinically significant benefit. Other results from randomized
      controlled trials (RCTs) are post-hoc subgroup analyses of larger trials.
      BENEFITS, HARMS AND COSTS: Screening mammography offers the potential for
      significant benefits in addition to mortality reduction, including early
      diagnosis, less aggressive therapy and improved cosmetic results. However, the
      risks of screening include increased biopsy rates and the psychological effects
      of false reassurance or false-positive results. Although several of the trials
      reviewed constitute level I evidence (RCT), at present their conflicting results,
      methodologic differences and, most important, uncertainty about the risk:benefit
      ratio of screening precludes the assignment of a "good" or "fair" rating to
      recommendations drawn from them. VALUES: The strength of evidence was evaluated
      using the methods of the Canadian Task Force on Preventive Health Care. A high
      value was placed on changes in survival. When evidence was available, value was
      also placed on potential quality-of-life implications. RECOMMENDATION: Current
      evidence regarding the effectiveness of screening mammography does not suggest
      the inclusion of the manoeuvre in, or its exclusion from, the periodic health
      examination of women aged 40-49 years at average risk of breast cancer (grade C
      recommendation). Upon reaching the age of 40, Canadian women should be informed
      of the potential benefits and risks of screening mammography and assisted in
      deciding at what age they wish to initiate the manoeuvre. VALIDATION: The
      findings of this analysis were reviewed through an iterative process by the
      members of the Canadian Task Force on Preventive Health Care. SPONSORS: The
      Canadian Task Force on Preventive Health Care is funded through a partnership
      between the Provincial and Territorial Ministries of Health and Health Canada.

PMID- 11233867
TI  - Physicians' prevention practices and incidence of neonatal group B streptococcal
      disease in 2 Canadian regions.
AB  - BACKGROUND: The impact of expert guidelines on the prevention of neonatal group B
      streptococcal (GBS) disease has not been studied in Canada. Our aim was to
      determine physician practices with regard to this condition before and after
      publication of Canadian guidelines and to monitor concurrent trends in the
      incidence of neonatal GBS disease. METHODS: We used repeat cross-sectional
      surveys, distributed by mail to all family practitioners and obstetricians
      attending deliveries in Alberta and in the Metropolitan Toronto and Peel region,
      Ontario, in 1994, 1995 and 1997, to document prevention practices. Audits were
      conducted for a subset of respondents to confirm reported practices. Population
      based surveillance involving all microbiology laboratories in both regions for
      1995-1998 was used to document rates of neonatal disease. RESULTS: The overall
      survey response rates were as follows: for 1994, 1128/1458 (77%); for 1995,
      1054/1450 (73%); and for 1997, 1030/1421 (72%). During 1995 and 1997,
      significantly more obstetric care providers were screening at least 75% of
      pregnant women in their practices than had been the case in 1994 (747/916 [82%]
      and 693/812 [85%] v. 754/981 [77%]; p < 0.001). The percentage of obstetric care
      providers who reported practice that conformed completely with any of 3 consensus
      prevention strategies increased from 10% in 1994 to 29% in 1997 (p < 0.001).
      There was a concurrent overall significant decrease in incidence of neonatal GBS
      disease during the same period. INTERPRETATION: The adoption by Canadian
      obstetric care providers of neonatal GBS prevention practices recommended by
      expert groups was slow but improved significantly over time. These findings
      highlight the difficulties associated with achieving compliance with diverse and
      frequently changing recommendations. However, the associated incidence of
      neonatal GBS disease, which was low or declining, suggests that efforts to
      disseminate current GBS prevention guidelines have been moderately successful.

PMID- 11233868
TI  - A call for an international ban on asbestos.

PMID- 11233869
TI  - A ban on asbestos must be based on a comparative risk assessment.

PMID- 11233870
TI  - Should Canadian health care professionals support the call for a worldwide ban on
      asbestos?

PMID- 11233871
TI  - Screening mammography for women aged 40-49: are we off the fence yet?

PMID- 11233872
TI  - Environment and health: 9. The science of risk assessment.

PMID- 11233873
TI  - Bioethics for clinicians: 23. Disclosure of medical error.
AB  - Adverse events and medical errors are not uncommon. In this article we review the
      literature on such events and discuss the ethical, legal and practical aspects of
      whether and how they should be disclosed to patients. Ethics, professional policy
      and the law, as well as the relevant empirical literature, suggest that timely
      and candid disclosure should be standard practice. Candour about error may
      lessen, rather than increase, the medicolegal liability of the health care
      professionals and may help to alleviate the patient's concerns. Guidelines for
      disclosure to patients, and their families if necessary, are proposed.

PMID- 11233875
TI  - Crackdown on hospital incinerators coming soon.

PMID- 11233876
TI  - CMAJ no longer just a Canadian journal, eCMAJ survey indicates.

PMID- 11233877
TI  - The epidemiology of murder: UK physician responsible for 345 deaths?

PMID- 11233874
TI  - The management of hypertension in Canada: a review of current guidelines, their
      shortcomings and implications for the future.
AB  - Clinicians are exposed to numerous hypertension guidelines. However, their
      enthusiasm for these guidelines, and the impact of the guidelines, appears modest
      at best. Barriers to the successful implementation of a guideline can be
      identified at the level of the clinician, the patient or the practice setting;
      however, the shortcomings of the guidelines themselves have received little
      attention. In this paper, we review the hypertension guidelines that are most
      commonly encountered by Canadian clinicians: the "1999 Canadian Recommendations
      for the Management of Hypertension," "The Sixth Report of the Joint National
      Committee on Prevention, Detection, Evaluation, and Treatment of High Blood
      Pressure" in the United States and the "1999 World Health Organization
      International Society of Hypertension Guidelines for the Management of
      Hypertension." The key points of these guidelines are compared and the
      shortcomings that may impede their ability to influence practice are discussed.
      The main implications for future guideline developers are outlined.

PMID- 11233878
TI  - Botulism in Canada.

PMID- 11233879
TI  - [Ultrasonography of the inferior vena cava (IVC) in the diagnosis and monitoring
      of therapy in patients with chronic congestive heart failure].
AB  - OBJECTIVE: This prospective clinical study investigated whether the relatively
      simple and cost-effective ultrasonography of the inferior vena cava (IVC)
      represents a valid clinical tool to assess the effectiveness of diuretic therapy
      in patients with chronic congestive heart failure (CHF). METHODS: Measurement of
      the resting and inspiratory diameter of the VCI repeatedly during diuretic
      therapy in 23 consecutive patients (11 women, 70 +/- 10 years) with CHF and
      comparing the results to the daily measured body weight and serum creatinine in
      these patients. Results were compared with the IVC diameter obtained in 33
      healthy controls (16 women, 42 +/- 15 years). In addition, the IVC collapse index
      was calculated to assess inspiratory movements of the IVC in patients on day 1
      and 10 of therapy. RESULTS: The IVC diameter at rest was 2.4 +/- 0.6 cm and
      decreased to 2.0 +/- 0.7 cm at inspiration, which was significantly greater than
      in healthy controls (1.4 +/- 0.4 cm at rest and 1.05 +/- 0.5 cm at inspiration; p
      = 0.008 and p = 0.01, respectively). The IVC diameter decreased continuously and
      significantly (p < 0.003) from day 1 to day 10 during diuretic therapy without a
      concomitant rise in serum creatinine. At beginning of therapy, the collapse-index
      of the IVC was significantly greater in patients than in controls. However, after
      10 days of therapy this index reached similar values to those observed in
      controls. CONCLUSION: Ultrasonographic measurements of IVC diameter and
      inspiratory movements are a quantifiable and reliable approach to assess the
      hypervolemia associated with CHF. Normalization of inspiratory IVC collapse
      movement correlates with successful diuretic therapy and can be reliably used for
      bedside assessment and monitoring treatment in CHF patients.

PMID- 11233880
TI  - [A young man with adynamia, subepicardial ischemia and sleep apnea].
AB  - HISTORY AND CLINICAL FINDINGS: A 44-year-old manager presented himself for the
      assessment of nocturnal apnoea. He reported increasing lack of drive and nightly
      angina pectoris. INVESTIGATIONS: Polysomnography indicated obstructive apnoea and
      hypopnoea with a respiratory disturbance index of 29.1, while the ECG showed T
      wave inversion in all leads. There was severe hypothyroidism with atrophic
      thyroid tissue. DIAGNOSIS, TREATMENT AND COURSE: The patient had an obstructive
      sleep apnoea syndrome (OSAS), hypothyroidism with myxoedema, hypopnoea and
      myocardial ischaemia. He was treated with negative peak airway pressure (nCPAP)
      ventilation, administration of L-thyroxine and initiation of anti-anginal
      medication, which relieved his symptoms. The severe hypothyroidism was thought to
      be the most important cause of his respiratory disorder and angina. CONCLUSION:
      This case illustrates the connection between hypothyroidism and OSAS.
      Hypothyroidism must be excluded in patients with OSAS, regardless of the
      patient's age.

PMID- 11233881
TI  - [Microbiological and immunological monitoring in polyarticular rheumatoid
      arthritis after total joint replacement].
AB  - HISTORY AND ADMISSION FINDINGS: A 51-year-old man with polyarticular rheumatoid
      arthritis since the age of 10 years, which had required three total joint
      replacements, presented in a generally good condition for replacement of the left
      elbow joint, which was swollen and had reduced movement. TREATMENT AND COURSE:
      The postoperative condition was without complication until the 7th day when
      arthritic signs set in, interpreted as part of the underlying disease, and
      cortisone was administered. After microbiological tests had been done and the
      patient's general state had deteriorated, antibiotic treatment with
      flucloxacillin and gentamycin as well as local irrigation and suction-drainage of
      all involved joints was started. Granulocyte and monocyte functions were
      analysed. Staphylococcal isolates from the patient induced reduced "respiratory
      burst" activity of the neutrophil granulocytes, apparently the cause of the
      septic dissemination. He was discharged on the 32. postoperative day, to be
      followed-up as an out-patient. CONCLUSION: Both adequate antibiotic
      administration and, especially, thorough local reduction of pathogens are needed
      for efficacious treatment. Rapid restoration of granulocyte function and of the
      "immunocompetence" of monocytes within normal limits are part of the reason for a
      good therapeutic response. This indicates the need for up-to-date preoperative
      immunological diagnosis in patients with suppressed immunity to assess the risk
      of infection and thus plan elective intervention.

PMID- 11233882
TI  - [Toxic epidermal necrolysis (drug-induced Lyell's syndrome). I. Clinical features
      and differential diagnosis].

PMID- 11233885
TI  - [Chlamydia infections in neurology].

PMID- 11233883
TI  - [Osteoprotegerin ligand and osteoprotegerin: new concepts of the pathogenesis and
      therapy of metabolic bone diseases].

PMID- 11233886
TI  - [PTCA in acute myocardial infarction?--Pro].

PMID- 11233884
TI  - [The "Furberg bias" or: about the arbitrary handling of evidence-based medicine].

PMID- 11233887
TI  - [PTCA in acute myocardial infarction?--Contra].

PMID- 11233888
TI  - ["The ignoramuses and the (megalo)-maniacs: the image of the physician in modern
      literature].

PMID- 11233889
TI  - [Generation change in beta-Interferon announced].

PMID- 11233890
TI  - [HCC: Adoptive immunotherapy promises success].

PMID- 11233891
TI  - PECAM-1/CD31: more than just glue.

PMID- 11233892
TI  - Inducing host acceptance to encapsulated xenogeneic myoblasts.
AB  - BACKGROUND: Cell encapsulation holds promise for the chronic delivery of
      recombinant proteins such as erythropoietin. Encapsulated xenogeneic mouse C2C12
      myoblasts display long-term survival in the central nervous system whereas they
      do not in the subcutaneous tissue, suggesting that encapsulation only partially
      prevents affector and effector mechanisms of the host immune response. Transient
      immunosuppression with FK506 at the time of subcutaneous implantation leads,
      however, to their long-term survival. The nature of this acceptance was further
      investigated in this report. METHODS: Fischer rats were rendered unresponsive to
      encapsulated murine C2C12 myoblasts secreting mouse erythropoietin by either a 1-
      or 4-week initial treatment of FK506. To examine the extent of xenograft
      acceptance, animal were challenged with a second implant 9 weeks after the
      initial implantation. RESULTS: Challenging animals treated only 1 week with FK506
      led to rejection of both primary and secondary implants. Animals administered
      FK506 for 4 weeks accepted both implants over the period investigated. However,
      these animals rejected unencapsulated xenogeneic cells injected at a later time,
      highlighting the requirement of the polymer membrane for immune protection.
      Developed unresponsiveness to encapsulated xenogeneic myoblasts lasted over
      extended periods (at least 7 months), in the absence of both immunosuppression
      and stimulating xenoantigens. CONCLUSIONS: These findings reveal that host
      acceptance of encapsulated but not unencapsulated xenogeneic myoblasts can be
      developed in the subcutaneous tissue after transient FK506 immunosuppression.
      This may have direct clinical relevance as it enables capsules to be replaced
      without additional immunosuppression, facilitating long-term cell-based
      therapies.

PMID- 11233893
TI  - "Chemical preconditioning" by 3-nitropropionate reduces ischemia-reperfusion
      injury in cardiac-arrested rat lungs.
AB  - BACKGROUND: Chemical preconditioning was defined as the induction of resistance
      to massive disruption of energy metabolism through prior chemical suppression of
      oxidative phosphorylation, by which phenomena similar to those resulting from
      increased ischemic tolerance as a result of ischemic preconditioning can be
      induced. It could be induced by the inhibitor of either mitochondrial complex I
      or II. We investigated whether or not chemical preconditioning by 3
      nitropropionate (an inhibitor of the mitochondrial complex II) can suppress
      ischemia-reperfusion injury in cardiac-arrested lungs, which will be the major
      problem in lung transplants donated from non-heart-beating cadavers. METHODS AND
      RESULTS: In an isolated rat lung perfusion model with fresh rat blood as
      perfusate, administration of 3-nitropropionate (20 mg/kg) immediately before the
      induction of cardiac arrest attenuated pulmonary dysfunction during reperfusion
      after 1 hr postmortem warm ischemia and 1 hr cold preservation. 3-Nitropropionate
      administration reduced the mitochondrial respiratory functions (state 3 and state
      4 respiration, and the respiratory control ratio) before cardiac arrest and kept
      them at a lower level of activity than when decreased by ischemia alone. 3
      Nitropropionate administration also reduced the ATP levels immediately after drug
      administration. However, 3-nitropropionate did not significantly reduce lipid
      peroxidation in the lung tissue and mitochondria. CONCLUSIONS: These results
      demonstrated that chemical preconditioning by 3-nitropropionate administration
      immediately before cardiac arrest suppressed succinate-related oxidation during
      postmortem warm ischemia and reduced ischemia-reperfusion injury in cardiac
      arrested rat lungs.

PMID- 11233894
TI  - Microchimerism does not induce tolerance and sustains immunity after in utero
      transplantation.
AB  - BACKGROUND: To date, over 40 in utero transplants have been performed in humans;
      the only successes were documented in the treatment of severe combined
      immunodeficiency syndromes. Hemoglobinopathies and metabolic disorders are
      candidate diseases for this approach; however, when applied clinically, the
      results have been discouraging. To address the role of the fetal immune system in
      the outcome of in utero transplantation, we have developed a murine model of in
      utero transplantation in immunologically intact murine recipients and have
      studied chimerism and tolerance/immunity to allogeneic donor cells through the
      lives of the animals. METHODS: We have performed experiments in which purified
      murine sca-1+/lin- cells and c-kit+/lin- cells of C57BL/6 (H2b) mice were
      injected into Balb/c (H2d) fetal recipients at early gestational ages. Chimerism
      was tested by highly sensitive semiquantitative polymerase chain reaction assay
      and tolerance/immunity to donor cells was studied by in vivo (skin grafts,
      responses to postnatal boosts) and in vitro (mixed lymphocyte culture,
      cytotoxicity, and cytokine release) assays. RESULTS: One hundred percent (10/10)
      of mice transplanted with c-kit+ cells and 44% (4/9) of mice transplanted with
      sca+ cells showed circulating donor cells within the first 6 months of life
      (P=0.031). Mice in the sca+ group rejected donor skin grafts at a mean time of
      9.1+/-0.2 days, whereas mice in the c-kit+ group rejected donor skin grafts at a
      mean time of 15.1+/-0.7 days (P=0.001). The difference between the transplanted
      groups and non-transplanted controls was also significant (P<0.05). All mice
      transplanted with sca+/lin- cells showed greater response to donor cells than to
      third-party cells at all effector to target ratios (P=0.002). Differences in
      response to donor alloantigen between sca+ and c-kit+ groups were significant
      (P=0.003). Cytokine quantification demonstrated higher TH1 than TH2 cytokine
      release in all groups, and the response to donor cells was higher in the sca+
      compared with c-kit+ mice (P=0.031). CONCLUSION: These results demonstrate a low
      level of chimerism and tolerance in mice transplanted in utero with sca+/lin- and
      c-kit+/lin- cells. The possibility of active in utero immunization to donor cells
      is supported by accelerated skin graft rejection in mice transplanted with sca+
      cells and enhanced in vitro immune responses in mice with persistent
      microchimerism.

PMID- 11233895
TI  - Long-term outcome of lung transplantation is predicted by the number of HLA-DR
      mismatches.
AB  - BACKGROUND: The importance of HLA mismatch in determining long-term outcome in
      lung transplantation remains largely uncertain. METHODS: A retrospective analysis
      of 102 consecutive primary lung transplants was performed to identify risk
      factors for poor long-term outcome after lung transplantation defined as graft
      survival and bronchiolitis obliterans syndrome (BOS) stage I and II. Variables
      included were patient characteristics (age, sex, prior diagnosis), the number of
      HLA mismatches between donor and recipient, cold ischemic time, cytomegalovirus
      serologic concordance, number of acute rejections, and time to first rejection.
      Variables carrying significance in a univariate analysis were subjected to a
      proportional hazard regression analysis. RESULTS: In the multivariate analysis,
      an increased number of acute rejections correlated positively with decreased
      graft survival (risk ratio [RR] = 1.25; 95% confidence interval [CI], 1.05-1.5; P
      = 0.011), development of BOS stage I (RR = 1.36/episode; 95% CI, 1.16-1.58;P <
      0.001), and BOS stage II (RR = 1.42/episode; 95% CI, 1.2-1.67; P < 0.001). An
      increased time to rejection correlated positively with reduced graft survival (RR
      = 1.03/day; 95% CI, 1.01-1.06; P = 0.02), and BOS stage I and II (both RR =
      1.04/day; 95% CI, 1.01-1.07; P < 0.005). Compared with 2 HLA-DR mismatches, 0 or
      1 mismatch was associated with improved graft survival (RR = 0.43; 95% CI, 0.19
      0.98; P = 0.045) and protected against development of BOS stage I (RR = 0.47; 95%
      CI, 0.23-0.98; P = 0.044) and BOS stage II (RR = 0.35; 95% CI, 0.15-0.83; P =
      0.017). CONCLUSIONS: HLA-DR mismatching appears to be a risk factor for the
      development of BOS and graft loss. Improved outcome after lung transplantation
      might be achieved with prospective matching for HLA-DR. Alternatively, the amount
      and type of immunosuppressive drugs may be guided by the degree of HLA-DR
      (mis)matching.

PMID- 11233896
TI  - Chimerism analysis by lineage-specific fluorescent polymerase chain reaction in
      secondary graft failure after allogeneic stem cell transplantation.
AB  - BACKGROUND: Chimerism analysis is essential in understanding the etiology of
      graft failure occurring after allogeneic stem cell transplantation. The detection
      of marrow and/or blood host cells suggests graft rejection, relapse of the
      underlying disease, or a state of stable mixed chimerism. However, complete donor
      chimerism may be observed in some cases. Our objective was to characterize, by a
      sensitive process of chimerism analysis, six cases of graft failure occurring
      after transplant. METHODS: Six cases of secondary graft failure, in which
      previous analysis had shown complete donor chimerism by standard polymerase chain
      reaction amplification of variable number of tandem repeats, were studied. In
      order to detect a minority population of recipient cells, we increased the
      sensitivity of the process by using fluorescent polymerase chain reaction and
      analyzing the origin of T, B, and natural killer lymphocytes at the time of graft
      failure. RESULTS: The complete donor origin of mononuclear cells and lymphocytic
      populations was confirmed with this method in five of six patients. In the
      remaining patient, diagnosis of graft failure was clarified by the detection of a
      previously undetected mixed chimerism, compatible with graft rejection. In the
      other five patients, graft rejection was thereby excluded and graft failure could
      be related to viral infection or to graft-versus-host disease. CONCLUSION: Our
      sensitive process of fluorescent lineage-specific chimerism analysis may help in
      distinguishing between graft rejection and other mechanisms of graft failure,
      which is essential for deciding appropriate therapy.

PMID- 11233897
TI  - Does renal mass exert an independent effect on the determinants of antigen
      dependent injury?
AB  - The aim of this retrospective study was to determine whether nephron mass may
      exert a direct, independent effect on immunological tolerance. To this end, data
      corresponding to patients transplanted with en block pediatric kidneys (EBPK)
      (n=48) were compared with those of renal transplants with a low risk of
      hyperfiltration (LRH) comprised of recipients of a kidney from young donors (age
      5-40 years) (n=173), and transplants with a high risk of hyperfiltration (HRH)
      comprised of patients who had received a graft from an elderly donor (older than
      55 years) (n=91). All the patients had been subjected to the same
      immunosuppressive treatment. The median follow-up period was 54 months (6-127
      months). The EBPK group showed lowest serum creatinine and highest creatinine
      clearance levels at each follow-up time. The rate of proteinuria >500 mg/day was
      5.7% in EBPK, 7.4% in LRH, and 27.3% in HRH (P=0.000). The incidence of acute
      corticoresistant rejection was minor in EBPK (7.0% in EBPK, 21.3% in LRH, and
      23.3% in HRH; P=0.04). Logistic regression analysis showed that the type of
      transplant was predictive of acute corticoresistant rejection [RR 5.33 (95%
      confidence interval (CI) 1.15-24.62) for HRH and RR 4.75 (95%CI 1.06-21.27) for
      LRH, P=0.03]. Multivariate analyses for graft failure due to chronic rejection
      and for graft failure due to acute rejection according to Cox's regression
      analysis demonstrated that HRH transplant was a significant predictive variable
      of both types of failure [4.08 (95%CI 1.27-13.04) for graft loss due to chronic
      rejection and 8.69 (95%CI 1.69-44.67) for graft loss due to acute rejection]. The
      present stratification of data according to nephronal mass would appear to
      indicate that the greater the mass, the lower the incidence of both acute and
      chronic rejection. This finding lends support to the hypothesis that a large mass
      of transplanted tissue relative to recipient mass may dampen the immune response.

PMID- 11233898
TI  - Results on preemptive or prophylactic treatment of lamivudine in HBsAg (+) renal
      allograft recipients: comparison with salvage treatment after hepatic dysfunction
      with HBV recurrence.
AB  - BACKGROUND: Lamivudine has been reported to be able to stabilize liver enzyme and
      hepatitis B virus (HBV) replication with recurrent hepatitis that has been
      regarded as a frequent and major risk factor for hepatic dysfunction and chronic
      liver disease in renal transplant recipients. Because large number of hepatitis
      antigenemia patients among renal transplant patients experience recurrent hepatic
      dysfunction with HBV recurrence and permanent histological deterioration,
      preemptive or primary prophylactic use of lamivudine before transplantation may
      be more beneficial than a trial for the treatment of advanced hepatic
      dysfunction. METHODS: We conducted a double arm study to compare the efficacy of
      lamivudine between the preemptive (HBV DNA positive) or prophylactic (HBV DNA
      negative) trial for the maintenance of stable liver function (n=10) and the trial
      for the salvage of advanced hepatic dysfunction developed after renal
      transplantation (n=6) in hepatitis B viremia carrier renal transplant recipients.
      RESULTS: Hepatic dysfunction with recurrent HBV antigenemia developed in 11 of 36
      (30.6%) hepatitis antigenemia patients with a mean duration of 8.4 months (range
      5-19.4 months). In six patients treated with lamivudine after hepatic dysfunction
      from recurrent hepatitis B viremia, serum AST and ALT level normalized within 1
      month and HBV-DNA disappeared in all cases. HBV-DNA, however, reappeared in three
      (50%) without any discontinuation of lamivudine. Liver biopsy revealed recurrent
      chronic active hepatitis with severe activity of fibrosis in four cases,
      cholestatic fibrosing hepatitis in one, and permanent cirrhotic change in one. In
      seven patients who had preemptive lamivudine treatment at 9, 6, 2, 2, 1, 0, 0
      month before the transplantation, HBV-DNA had converted to negative with a mean
      follow up of 1.2 months (range 1-2 month) in all case. Three patients who had
      prophylactic trials with lamivudine have all remained HBV-DNA negative. The
      recurrence rate of HBV viremia in the preemptive or prophylactic lamivudine
      treated group is 10.0% (1/10), which is significantly lower than that (42.3%,
      11/25) in the nonlamivudine-treated group. The re-recurrence rate of HBV viremia
      was significantly higher (3/6, 50.0%) in the reactive lamivudine treated group
      than in prophylactic or preemptive group (1/10, 10%). CONCLUSION: Although
      lamivudine treatment after hepatic dysfunction can be a sound conventional
      treatment modality, this preliminary study may suggest that preemptive or
      prophylactic trial of lamivudine before hepatic dysfunction might be a more
      effective strategy for prevention of permanent histological deterioration and
      recurrence of hepatitis B viremia.

PMID- 11233899
TI  - Clinical evaluation of a new recombinant antigen-based cytomegalovirus
      immunoglobulin M immunoassay in liver transplant recipients.
AB  - BACKGROUND: Human cytomegalovirus (CMV) is a significant cause of morbidity and
      mortality among transplant recipients. Monitoring transplant recipients by CMV
      IgM serology has been questioned by several studies due to the reported
      insensitivity of serologic tests relative to antigen detection methods. METHODS:
      In this retrospective study, we have evaluated the performance of the new
      recombinant antigen-based Abbott AxSYM CMV IgM assay and compared it with CMV
      culture technique in a cohort of 40 liver transplant recipients who did not
      receive antiviral prophylaxis. RESULTS: The sensitivity, specificity, and
      positive and negative predictive values for detection of CMV disease by the AxSYM
      CMV IgM assay were 90.0%, 60.0%, 69.2%, and 85.7%, respectively, and by culture
      the values were 100%, 55.0%, 69.0%, and 100%, respectively. Detection of CMV IgM
      occurred before or at the time of CMV disease in only R+ recipients. CONCLUSION:
      Although this assay is a sensitive test for CMV-specific IgM, detection of CMV
      IgM preceded detection of virus by culture in patients only when the liver
      transplant recipient was CMV immune before transplantation (R+).

PMID- 11233900
TI  - Interaction of mycophenolate mofetil and HLA matching on renal allograft
      survival.
AB  - INTRODUCTION: The importance of HLA matching for renal transplantation outcomes
      has been appreciated for several decades. It has been hypothesized that as
      pharmacologic immunosuppression becomes stronger and more specific, the impact of
      HLA matching may be vanishing. Mycophenolate Mofetil (MMF) has been demonstrated
      to both decrease acute rejection and improve three-year graft survival. It is
      possible that with new immunosuppressive regimens containing MMF the relative
      effect of HLA matching may be altered. To determine the relative impact of HLA
      matching in patients on MMF we undertook an analysis of the United States Renal
      Transplant Data Registry (USRDS). METHODS: All primary, solitary renal
      transplants registered at the USRDS between January 1995 and June 1997, on
      initial immunosuppression that included either MMF or AZA were followed until
      June 1998. Primary study end points were graft and patient survival. Kaplan-Meier
      analysis was performed to compare AZA vs. MMF treated patients by HLA mismatch.
      Cox proportional hazard models were used to investigate the interaction between
      HLA mismatch and AZA versus MMF therapy on the study endpoints. All multivariate
      analyses were corrected for 13 potential confounding pretransplant variables
      including intention to treat immunosuppression. RESULTS: A total of 19,675
      patients were analyzed (8,459 on MMF and 11,216 on AZA). Overall three year graft
      survival was higher in the MMF group when compared to the AZA group (87% vs. 84%
      respectively P<0.001). For both AZA and MMF three-year graft survival improved
      with fewer HLA donor-recipient mismatches. Comparing zero antigen mismatches to
      six antigen mismatches, the relative improvement was comparable for both patients
      on AZA (92.4% vs. 80.6%) and MMF (95.2% vs. 82.9%). By Cox proportional hazard
      model the relative risk for graft loss decreased significantly in both the AZA
      and MMF treated patients with increased HLA matching. CONCLUSION: The use of MMF
      does not obviate the benefits of HLA matching, while HLA matching does not
      minimize the benefits of MMF on long term graft survival. Our study would suggest
      that HLA matching and MMF therapy are additive factors in decreasing the risk for
      renal allograft loss.

PMID- 11233901
TI  - Reduced transfusion requirements by recombinant factor VIIa in orthotopic liver
      transplantation: a pilot study.
AB  - BACKGROUND: Large transfusion requirements, i.e., excessive blood loss, during
      orthotopic liver transplantation (OLT) are correlated with increased morbidity
      and mortality. Recombinant factor VIIa (rF-VIIa) has been shown to improve
      hemostasis in a variety of conditions, but has never been studied in liver
      transplantation. METHODS: We performed a single-center, open-label, pilot study
      in adult patients undergoing OLT for cirrhosis Child-Pugh B or C, to assess
      efficacy and safety of rFVIIa. rFVIIa (80 microg/kg) was administered at the
      start of the operation, to be repeated according to predefined criteria. Packed
      red blood cells (RBC), fresh-frozen plasma, and platelet concentrates were
      administered according to predefined criteria. Perioperative transfusion
      requirements in study patients were compared with matched controls. RESULTS: Six
      patients were enrolled in the study. All received a single dose of rFVIIa.
      Transfusion requirements (given as median, with range in parentheses) were lower
      in the study group than in matched controls: 1.5 (0-5) vs. 7 (2-18) units of
      allogeneic RBC (P=0.006), 0 (0-2) vs. 3.5 (0-23) units of autologous RBC
      (P=0.043), total amount of RBC 3 (0-5) vs. 9 (4-40) units (P=0.002). Transfused
      fresh-frozen plasma was 1 (0-7) vs. 8 (2-35) units (P=0.011). Blood loss was 3.5
      L (1.4-5.3) vs. 9.8 L (3.7-35.0) (P=0.004). One study patient developed a hepatic
      artery thrombosis at day 1 postoperatively. CONCLUSIONS: A single dose of 80
      microg/kg rFVIIa significantly reduced transfusion requirements during OLT.
      Further study is needed to establish the optimally effective and safe dose of
      rFVIIa in orthotopic liver transplantation.

PMID- 11233902
TI  - Thyroid function after bone marrow transplantation: possible association between
      immune-mediated thyrotoxicosis and hypothyroidism.
AB  - BACKGROUND: Thyroid dysfunction after bone marrow transplantation (BMT) has been
      investigated in many studies, and most posttransplant thyroid disorders are now
      recognized as a late complication of transplantation. However, these studies
      mainly focused on late thyroid function after BMT, and we have little information
      on early changes of thyroid function after BMT. METHODS: We prospectively
      investigated thyroid function in 57 patients receiving BMT. Serum thyroid
      stimulating hormone, free triiodothyronine, and free thyroxine levels were
      determined at least monthly in the first 3 months, once between 3 and 12 months
      and once in the second year after BMT. RESULTS: During the first 6 months after
      BMT, 24 and 7 patients were diagnosed as having euthyroid sick syndrome (ETS) and
      thyrotoxicosis, respectively. Of the 52 patients alive 1 year after
      transplantation, 9 patients were still diagnosed as having ETS, and 8 patients
      developed hypothyroidism. Patients with thyrotoxicosis showed similar
      characteristics, and the high incidence of thyrotoxicosis after BMT is a novel
      finding. The median for the onset of thyrotoxicosis was day 111 after
      transplantation. Thyrotoxicosis was transient in all of the patients, but in
      seven patients hypothyroidism followed, the median onset at 12 months after BMT.
      Serum thyroglobulin levels were elevated in five patients, and antibodies
      autoreactive to the thyroid gland were detected in seven patients. CONCLUSIONS:
      Thyrotoxicosis may be a distinct clinical entity of thyroid dysfunction after BMT
      and may serve to predict the development of hypothyroidism. Immune-mediated
      thyroid injury may contribute to the development of posttransplant
      hypothyroidism.

PMID- 11233903
TI  - Comparison between antigenemia and a quantitative-competitive polymerase chain
      reaction for the diagnosis of cytomegalovirus infection after heart
      transplantation.
AB  - BACKGROUND: Antigenemia and quantitative polymerase chain reaction (PCR) are
      widely used for cytomegalovirus (CMV) diagnosis after heart transplantation due
      to their enhanced predictive values for disease detection when specific cut-off
      values are used. The purpose of this study was to compare, in the same patient
      setting, the predictive values of quantitative PCR and antigenemia for CMV
      disease detection, using specific cut-off values. METHODS: Thirty heart
      transplant receptors were ch prospectively monitored for active CMV infection and
      disease detection, using quantitative PCR and anti- po genemia. Positive and
      negative predictive values for pr CMV disease detection were calculated using cut
      off pr values for both antigenemia (5 and 10 positive cells/300,000 neutrophils)
      and quantitative-PCR (50,000 and 100,000 copies/10(6) leukocytes). RESULTS:
      Active CMV infection was diagnosed in 93.3% of patients and CMV disease in 23.3%.
      The positive and negative predictive (%) values for CMV disease detection were
      35/100 and 46.7/100, respectively, for quantitative PCR and antigenemia. Using 5
      and 10 positive cells/300,000 neutrophils as cut-off values for antigenemia, the
      positive and negative predictive values (%) for disease detection were
      respectively 63.6/100 and 70/100. For quantitative PCR, the positive and th
      negative predictive values (%) for cut-off values of to 50,000 and 100,000
      copies/10(6) leukocytes were 53.8/100 and 60/94.1, respectively. CONCLUSION: In
      our series, antigenemia and quantitative-PCR had enhanced and similar predictive
      values for CMV disease detection when specific cut-off values were used. The
      choice between these two methods for disease detection may rely less on their
      efficiency and more on the experience and familiarity with them.

PMID- 11233904
TI  - Indirectly primed CD8+ T cells are a prominent component of the allogeneic T-cell
      repertoire after skin graft rejection in mice.
AB  - BACKGROUND: Alloreactive CD4 and CD8 T lymphocytes recognize antigen through both
      the direct and the indirect pathways. Although indirect priming of CD4+ T cells
      has been well described, little is known about the frequency and cytokine profile
      of indirectly primed CD8+ T cells during fully allogeneic graft rejection.
      METHODS: We used a cytokine enzyme-linked immunosorbent spot assay to
      characterize indirect priming of alloreactive CD8 and CD4 cells in mice. RESULTS:
      Interferon-gamma-producing CD8+ T cells specific for indirectly presented
      alloantigen were detectable in allograft-primed mice at a frequency of 50-100 per
      million cells (compared with 3000 per million for responses through the direct
      pathway) and were similar in frequency to indirectly primed CD4 cells.
      CONCLUSION: CD8+ T cells primed through the indirect pathway are a prominent
      component of the alloreactive T-cell repertoire induced after skin graft
      placement in mice, raising the possibility that these cells may play a
      significant role in the rejection process itself.

PMID- 11233905
TI  - Improved flow cytometric detection of HLA alloantibodies using pronase: potential
      implications in renal transplantation.
AB  - BACKGROUND: Flow cytomeric crossmatch (FCXM) has grown in popularity and has
      become the "standard of practice" in many programs. Although FCXM is the most
      sensitive method for detecting alloantibody, the B cell FCXM has been
      problematic. Difficulties with the B cell FCXMs have been centered around high
      nonspecific fluorescence background owing to Fc-receptors present on the B cells
      and autoantibodies. To improve the specificity and sensitivity of the B cell
      FCXM, we utilized the proteolytic enzyme pronase to remove Fc receptors from
      lymphocytes before their use in FCXM. METHODS: Lymphocytes isolated from
      peripheral blood, spleen, or lymph nodes were treated with pronase and then used
      in a three-color FCXM. A total of 167 T- and B cell FCXMs using pronase-treated
      and untreated cells were performed. Testing used serial dilutions of HLA allosera
      (22 class I and 6 class II), with the titer of each antibody at one dilution past
      the titer at which the complement-mediated cytotoxicity anti-human globulin
      crossmatch became negative. RESULTS: After pronase treatment, the actual channel
      values of the negative control in both T cell and B cell FCXMs declined from 78+/
      10 to 57+/-4 (P<0.05) and 107+/-11 to 49+/-3 (P<0.00001), respectively. Pronase
      treatment resulted in improved sensitivity of the T and B cell FCXM in detecting
      class I antibody by 20% and 80%, respectively. In no instance was a false
      positive reaction observed. In this study, pronase treatment improved the
      specificity of B cell FCXM for detecting class II antibodies from 75% to 100%
      (P=0.03). In no instance was a false-negative reaction recorded. Lastly, on the
      basis of these observations we re-evaluated three primary transplant recipients
      who lost their allografts because of accelerated rejection. One of the patients
      was transplanted across negative T and B cell FCXM, whereas the other two
      patients were transplanted across a positive T cell, but negative B cell, FCXM.
      After pronase treatment, T and B cell FCXMs of each patient became strongly
      positive, and donor-specific anti-HLA class I antibody was identi. fied in each
      case. CONCLUSION: Utilization of pronase-treated lymphocytes improves both the
      sensitivity and specificity of the FCXM.

PMID- 11233906
TI  - Gender differences in the risk for chronic renal allograft failure.
AB  - BACKGROUND: Despite the known differences in immunological reactivity between
      males and females, no differences in graft survival have been described among
      renal transplant recipients with regard to gender. To address this paradox, we
      analyzed data from 73,477 primary renal transplants collected in the US Renal
      Data System database. METHODS: Logistic regression and Cox proportional hazard
      models were used to investigate the primary study end points, graft loss
      secondary to acute rejection (AR) or chronic allograft failure (CAF). CAF was
      defined as graft loss beyond 6 months, not attributable to death, recurrent
      disease, acute rejection, thrombosis, infection, noncompliance, or technical
      problems. The models adjusted for 15 covariates including immunosuppressive
      regimen, and donor and recipient characteristics. RESULTS: The overall 8-year
      graft and patient survivals were significantly better in female renal transplant
      recipients compared with male recipients. However graft survival censored for
      death was not significantly different by gender. By multivariate analysis,
      females had a 10% increased odds of AR (OR=1.10, CI 1.02-1.12), but conversely a
      10% lower risk of graft loss secondary to CAF (RR=0.9, CI 0.85-0.96). The risk
      for CAF increased significantly with increasing age for both males and females,
      but this effect was greater for males than for females (P<0.001). CONCLUSION:
      Although female renal transplant recipients have a similar death censored graft
      survival compared with males, there are important differences in immunological
      behavior. Females have a higher risk of AR while having a decreased risk of graft
      loss secondary to CAF.

PMID- 11233907
TI  - T cell mixed chimerism is significantly correlated to a decreased risk of acute
      graft-versus-host disease after allogeneic stem cell transplantation.
AB  - BACKGROUND: It has been debated whether mixed chimerism (MC) is correlated to a
      decreased incidence of graft-versus-host disease (GVHD) after allogeneic stem
      cell transplantation (SCT). METHODS: Between September 1996 and April 1999 we
      analyzed 102 patients for MC in the T-cell fraction post allogeneic SCT, using
      PCR amplification of variable numbers of tandem repeat (VNTR) loci. All samples,
      taken regularly post SCT, were cell separated using anti-CD3 immunomagnetic
      beads. RESULTS: T-cell mixed chimerism was detected in 58 out of 102 patients
      (57%). Patient characteristics were comparable in the T-cell MC- and donor
      chimeric-group (DC). The median follow-up time for the MC group was 714 days
      (range 58 - 1248) as compared to 427 days (range 45 - 1042) for the DC group.
      Overall probability of acute GVHD grades II-IV was significantly higher in the DC
      group as compared to the MC group (52% vs. 5%, P<0.001). In multivariate analysis
      T-cell DC proved to be the most significant risk factor for acute GVHD grades II
      IV. The cumulative incidence of relapse, among patients with malignant disease,
      did not show any statistical difference between the T-cell MC patients and the DC
      group. There was a tendency for better overall survival in the T-cell MC group
      compared to the DC group (2 yrs; 73% vs. 54%, P=0.06). Among DC patients, 14/20
      (70%) deaths were due to GVHD versus none in the MC-group(P<0.001). CONCLUSION: T
      cell mixed chimerism was significantly correlated to a decreased risk of moderate
      to severe acute GVHD and death by GVHD.

PMID- 11233908
TI  - Biophysical characteristics of anti-Gal(alpha)1-3Gal IgM binding to cell
      surfaces: implications for xenotransplantation.
AB  - BACKGROUND: Natural antibodies directed against cell surface carbohydrates are
      thought to be vital to host defense and to initiate the rejection of xenografts
      and ABO-incompatible allografts. The biophysical properties underlying the
      association and dissociation of these antibodies from cell surfaces is
      incompletely understood. We investigated those properties for the binding of
      Galalpha1-3Gal antibodies to porcine endothelial cell surfaces, because such
      interactions might be relevant to the clinical application of
      xenotransplantation. RESULTS AND CONCLUSIONS: The initial rate of binding of anti
      Galalpha1-3Gal antibodies to endothelial cells was found to depend on antibody
      concentration, antibody diffusion, and antigen concentration. The presence of an
      intact glycocalyx had a greater impact on antibody binding than mobility of
      antigen in cell membranes. Disruption of glycocalyx increased the amount of
      antibody bound at equilibrium by more than 50%. Although the binding of anti
      Galalpha1-3Gal antibodies to cell surfaces could be inhibited by soluble
      Galalpha1-3Gal, once bound, some anti-Galalpha1-3Gal could not be dissociated by
      competitive inhibitors of binding or by denaturation of the bound Ig with
      chaotropic reagents, but could be dissociated by reduction of disulfide bonds,
      suggesting that attachment to cell surfaces was, at least in part, by means other
      than specific reaction with the epitope.

PMID- 11233909
TI  - Cyclophosphamide-induced tolerance in rat orthotopic liver transplantation.
AB  - BACKGROUND: We previously established a cyclophosphamide (CP)-induced tolerance
      system in rodent skin graft models. In this study, we applied this system to rat
      liver transplantation. METHODS: Lewis recipients were inoculated on day -2 with
      spleen and bone marrow cells (SC+BMC) from Dark Agouti (DA) donors, followed by
      100 mg/kg CP on day 0. On day 25, DA livers were orthotopically grafted. We
      assessed the alloresponses to the donors of the long-term surviving recipients,
      using the second skin grafting and in vitro assay. RESULTS: The recipients that
      had been treated with SC+BMC and CP survived for more than 165 days. None of
      control group that received SC+BMC alone (mean survival times [MST]=13.8 days),
      CP alone (MST=40.0), SC+BMC from third-party PVG rats and CP (MST=45.0), or no
      treatment (MST=13.8) survived over 50 days. The donor-specific tolerance was
      confirmed by second skin grafts onto recipients with permanent DA liver grafts,
      which accepted DA skins (MST>75) but not PVG (MST=8.3). However, the lymphocytes
      from the tolerant recipients showed alloresponse to DA in vitro. To investigate
      whether the T helper type 2 deviation contributed to this "split tolerance," we
      assessed the production of cytokines in mixed lymphocyte reaction. Interleukin 2
      and interferon-gamma were detected but interleukin 4 was not. CONCLUSIONS: These
      data showed that this protocol induced split tolerance in rat liver
      transplantation and, furthermore, the mechanism of split tolerance was not due to
      T helper 2 deviation.

PMID- 11233910
TI  - Signaling through CD31 protects endothelial cells from apoptosis.
AB  - Endothelial damage has been implicated in the pathogenesis of chronic rejection.
      Conversely, expression of protective genes [including A20, A1, bcl-xl, and
      hemoxygenase-1 (HO-1)] in the endothelium has been associated with long-term
      graft survival. Overexpression of protective genes in cultured endothelial cells
      confers protection from apoptosis and prevents expression of inflammatory
      molecules through inactivation of NF-kappaB. CD31 (PECAM-1) expressed at
      endothelial cell junctions is ligated by leukocytes during transendothelial
      migration. Our laboratory has recently shown that cross-linking CD31 using a
      monoclonal antibody (LCI-4) triggers signaling events in endothelial cells. In
      this study, we demonstrate that treatment with LCI-4 protected serum-starved
      endothelial cells from apoptosis. CD31 cross-linking also led to elevation of A20
      and A1 mRNA levels and activation of the transcription factor Sp-1. In summary,
      signaling through CD31 on endothelial cells leads to protection from apoptosis in
      association with up-regulation of two protective molecules, A20 and A1.

PMID- 11233911
TI  - Mechanisms involved in antithymocyte globulin immunosuppressive activity in a
      nonhuman primate model.
AB  - BACKGROUND: The mechanisms of action of polyclonal antithymocyte globulins (ATGs)
      are still poorly understood and the selection of doses used in different clinical
      applications (prevention or treatment of acute rejection in organ allografts,
      treatment of graft-versus-host disease, or conditioning for allogeneic stem cell
      transplantation) remains empirical. Low T-cell counts are usually achieved in
      peripheral blood during ATG treatment but the extent of T-cell depletion in
      lymphoid tissues is unknown. METHODS: Experiments were conducted in cynomolgus
      monkeys using Thymoglobuline at low (1 mg/kg), high (5 mg/kg), and very high (20
      mg/kg) doses. RESULTS: ATG treatment induced a dose-dependent lymphocytopenia in
      the blood and a dose-dependent T-cell depletion in spleen and lymph nodes but not
      in the thymus, indicating a limited access of ATG to this organ. T-cell apoptosis
      in peripheral lymphoid tissues was the main mechanism of depletion. Remaining T
      cells in peripheral lymphoid organs were coated by antibodies and had down
      modulated surface expression of CD2, CD3, CD4, and CD8 molecules, whereas their
      responsiveness in mixed leukocyte reaction was impaired. The survival of MHC
      mismatched skin and heart allografts was prolonged in a dose-dependent fashion,
      despite the occurrence of a strong anti-ATG antibody response resulting in the
      rapid clearance of circulating ATGs. CONCLUSION: The results indicate that T-cell
      depletion is achieved rapidly and primarily in peripheral lymphoid tissues at
      high ATG dosage. Short ATG treatments could therefore be clinically evaluated
      when major peripheral T-cell depletion is required.

PMID- 11233912
TI  - Donor cytokine genotype influences the development of acute rejection after renal
      transplantation.
AB  - BACKGROUND: Acute allograft rejection remains an important cause of morbidity
      after kidney transplantation, and has been shown to be a crucial determinant of
      long-term graft function. Although rejection is mediated by recipient
      lymphocytes, both donor and recipient factors contribute to the local environment
      that influences the nature, severity, and duration of the rejection response.
      Cytokines are a major determinant of this milieu, and this study sought to
      explore the impact of donor cytokine and cytokine receptor gene polymorphisms on
      acute rejection after renal transplantation. METHODS: A total of 145 cadaveric
      renal allograft donors were selected for analysis according to the presence or
      absence of graft rejection in the first 30 days after transplantation. DNA was
      genotyped for 20 polymorphisms in 11 cytokine and cytokine receptor genes using
      the polymerase chain reaction with sequence specific primers. Associations were
      assessed using contingency table analysis and the chi2 test, using a two-set
      design. RESULTS: A polymorphism at position -174 of the donor IL-6 gene was
      associated with the incidence (P=0.0002) and severity (P=0.000007) of recipient
      acute rejection. This finding was independent of HLA-DR matching. Acute rejection
      was not influenced by recipient IL-6 genotype, or by donor-recipient matching of
      IL-6 genotype. CONCLUSION: This study identifies donor IL-6 genotype as a major
      genetic risk factor for the development of acute rejection after renal
      transplantation. This provides evidence that donor-derived cytokines play a major
      role in determining outcome after transplantation, and will contribute to the
      development of therapeutic algorithms to predict individuals at particularly high
      risk of acute rejection.

PMID- 11233913
TI  - Rapid decline of antibodies after hepatitis A immunization in liver and renal
      transplant recipients.
AB  - BACKGROUND: Hepatitis A vaccine is safe and achieves good seroconversion rates in
      liver (LTX) and renal (RTX) transplant recipients. METHODS: A study was performed
      to determine the anti-hepatitis A virus (HAV) antibody decline in LTX and RTX
      patients, and in healthy controls who have been immunized with two doses of
      hepatitis A vaccine. RESULTS: LTX and RTX patients had a satisfactory
      seroconversion rate after complete immunisation. However, 2 years later they had
      experienced a much more rapid antibody decline than controls, and only 59% of LTX
      and 26% of RTX seroconverters showed titres above the cut-off level defined as
      protective. CONCLUSIONS: Patients on immunosuppressive therapy may not be
      adequately protected against hepatitis A a few years after vaccination and
      alternative vaccination schemes may have to be considered.

PMID- 11233914
TI  - Non-typhoid Salmonella septicemia and visceral leishmaniasis in a renal
      transplant patient.
AB  - BACKGROUND: We report on a renal transplant patient with recurrent attacks of
      fever, in which Salmonella septicemia as well as visceral leishmaniasis were
      diagnosed. PATIENT: The patient was a 62-year-old man with diabetic nephropathy
      and a living related kidney transplantation. RESULTS: Nearly 2 years after the
      transplantation, the patient developed recurrent attacks of fever, which were
      initially diagnosed as non-typhoid salmonellosis and improved after treatment.
      Three months later, he had relapses of fever. As the patient developed
      pancytopenia, a bone marrow aspiration was done, showing Leishmania parasites.
      The patient responded well to treatment with sodium stibogluconate. CONCLUSIONS:
      A high index of suspicion, together with better diagnostic assays to detect
      visceral leishmaniasis, is warranted in the diagnostic work-up of any fever of
      unknown origin in immunocompromised patients, especially in endemic areas.

PMID- 11233915
TI  - Elimination of alloantibodies by immunoablative high-dose cyclophosphamide.
AB  - BACKGROUND: Alloimmunization is a major problem for patients being considered for
      solid organ transplantation and in patients who require blood transfusion
      support. We previously demonstrated that high-dose cyclophosphamide (200 mg/kg)
      without hematopoietic stem cell transplantation leads to durable complete
      remissions in aplastic anemia and other autoimmune disorders. We now examine the
      ability of high-dose cyclophosphamide to eliminate alloreactivity. METHODS: IgG
      specific antibodies to HLA class I were assayed using enzyme-linked immunosorbent
      assays in 18 consecutive patients with severe aplastic anemia before and after
      treatment with high-dose cyclophosphamide. RESULTS: Anti-HLA antibodies were
      detected before or shortly after therapy in 5 of the 18 patients studied.
      Complete remission of aplastic anemia was achieved in four of these five
      patients. High-dose cyclophosphamide markedly reduced anti-HLA antibody titers in
      these four patients; they were completely eradicated in three patients. Only one
      patient did not achieve significant reduction in the alloantibody titer after
      high-dose cyclophosphamide. CONCLUSIONS: High-dose cyclophosphamide without stem
      cell transplantation can eradicate HLA-specific alloantibody.

PMID- 11233916
TI  - Ureteral obstruction in a transplant kidney caused by an ovarian tumor.
AB  - Ureteral obstruction in the transplant recipient can provide a diagnostic
      challenge. We report a case of ureteral obstruction 5 years after cadaveric renal
      transplantation due to an ovarian tumor. Magnetic resonance imaging provided
      essential anatomic information that eventually led to the diagnosis. To our
      knowledge, this is the first reported case of ureteral obstruction in a
      transplant kidney caused by an ovarian tumor.

PMID- 11233917
TI  - Transfusion of peripheral blood stem cells from donor homozygous for a shared HLA
      haplotype: avoiding fatal transfusion-associated graft-versus-host disease while
      preserving anti-leukemic effect.
AB  - BACKGROUND: Fatal transfusion-associated graft-versus-host disease was observed
      in immunocompetent patients transfused with blood from donors homozygous for a
      shared haplotype with the recipient (the P-F1 barrier). We tested whether it was
      possible to carry out successful transplantation in a patient with relapsed acute
      myeloid leukemia, using peripheral blood stem cells from his HLA-homozygous
      brother (HLA A2, B46, DRB1 901) who shared a haplotype with the patient (HLA A2,
      B46,75, DRB1 901,12). METHODS: A CD34 positively selected cell fraction (5.46x
      10(6) CD34 cells/kg) was infused first, followed by subsequent infusion of graded
      doses of donor T cells (total 7.25x10(7) T cells/kg). Nonmyeloablative
      chemotherapy with idarubicin and cytarabine was given during the transplantation
      to reduce the leukemic burden and facilitate engraftment. Polymerase chain
      reaction with the VNTR primers, D1S80, was used to detect engraftment. RESULTS:
      Complete remission (>300days) and successful donor engraftment (90%) were
      achieved. CONCLUSIONS: Peripheral blood stem cells transplantation from a donor
      with a homozygous shared haplotype is possible with a minimal preparative
      regimen.

PMID- 11233918
TI  - Anti-CD154 monoclonal antibody and thromboembolism.

PMID- 11233919
TI  - A novel approach for the quantitative kinetic study of reactions at solid/liquid
      interfaces in the presence of power ultrasound.
AB  - A novel cell and procedure is described which permits the quantitative
      mechanistic study of ultrasonically enhanced reactions which occur at
      solid/liquid interfaces. A model of a controlled and calculable time-average rate
      of mass transport to and from the interface is used in order to compare
      experimental results with theoretical predictions based on mechanistic reaction
      schemes. In this way concentrations of mechanistically significant species near
      the interface can be related to those in bulk solution and hence the sonochemical
      effects of ultrasound dissected from those arising purely from mass transport.
      The effect of ultrasound is demonstrated for the reaction dissolution of p
      chloranil in the presence of aqueous base and for the reaction of the same
      substrate with the aromatic amine, N,N-dimethyl-phenylenediamine, both systems
      which have been studied previously in the absence of ultrasound. Complementary
      atomic force microscopy images are also reported.

PMID- 11233920
TI  - Ultrasonic effects on electroorganic processes Part 6. Formation of cupric
      carboxylates at a reactive copper anode in carboxylic acid solutions.
AB  - Current efficiency for the formation of highly soluble cupric acetate at a
      reactive (consumable) copper anode in an acetic acid solution was increased
      almost independently of current density under ultrasonic irradiation. On the
      other hand, the efficiency for sparingly soluble cupric oxalate depended
      complicatedly on current density. At a low current density region less than 4 mA
      cm(-2), ultrasonic irradiation caused an increase in the current efficiency,
      while at higher current densities no ultrasonic effect was observed because of
      the formation of a rigid oxalate film on the anode surface. This paper is the
      first report of ultrasonic effects on an electrochemical reaction at a reactive
      (consumable) anode which is stoichiometrically involved in the reaction leading
      to the formation of products derived from anode metal.

PMID- 11233921
TI  - Ultrasonically enhanced corrosion of 304L stainless steel I: the effect of
      temperature and hydrostatic pressure.
AB  - A systematic study of the effect exerted by various parameters on the corrosion
      of 304L stainless steel in an ultrasonic field has been carried out. Ultrasound
      increased the corrosion rate under all the investigated conditions. In this
      paper, attention is focused on the effect of temperature and hydrostatic
      pressure. At ambient pressure, increase in temperature, T, was found to increase
      the ultrasonically enhanced corrosion rate up to a maximum of 40 degrees C; at 50
      degrees C a marked decrease in the effect of ultrasound was observed. At constant
      temperature, increase in hydrostatic pressure caused a strong increase in
      corrosion rate to values in excess of 2500 mm yr(-1) at 4 bar.

PMID- 11233922
TI  - Ultrasonically enhanced corrosion of 304L stainless steel II: the effect of
      frequency, acoustic power and horn to specimen distance.
AB  - The effects of frequency in the range 20 to 60 kHz, acoustic power and horn to
      specimen distance on the corrosion of 304L stainless steel in an ultrasonic field
      were investigated. At 40 and 60 kHz, the corrosion rate increased to a maximum
      and thereafter decreased with increasing transmitted power. At 20 kHz, the
      corrosion rate increased continuously with increasing power over the range
      investigated. At 18 W transmitted power, the corrosion rate increased
      continuously with frequency. However, at 40 W transmitted power a pronounced
      maximum in the corrosion rate occurred at 40 kHz. A significant effect of horn to
      specimen distance was found, the corrosion rate increasing with decreasing
      distance. High corrosion rates in excess of 800 mm yr(-1) were observed when the
      specimen was situated 0.1 mm from the radiating face of the ultrasonic probe. In
      addition, the area affected by sonication was found to increase with increasing
      distance.

PMID- 11233923
TI  - Ultrasound improves electrolytic recovery of metals.
AB  - Ultrasound has been shown to improve the cathodic current efficiency of copper
      electrodeposited from a dilute acidic sulphate bath and also zinc from a dilute
      alkaline zincate bath. Depending upon the plating parameters the metal may be
      plated with an enhanced value as a foil, sheet or powder. This agitation may be
      utilised in the recovery of metal from waste solutions and also in the recycling
      of acids and alkalies.

PMID- 11233924
TI  - Sonochemical production of a non-crystalline phase of palladium.
AB  - A non-crystalline phase of palladium was produced by cavitation technique
      starting from a solution of palladium acetylacetonate and toluene. The
      microscopic structure of the sample, a very fine powder, was investigated by X
      ray diffraction and it showed the characteristic features of a disordered system.
      Further details about the phase of the sample were gained by studying the
      crystallization process induced by thermal treatments.

PMID- 11233925
TI  - The effect of frequency on sonochemical reactions III: dissociation of carbon
      disulfide.
AB  - Investigations were made of the effects of frequency, temperature, intensity and
      gases on the rate of sonochemical dissociation of carbon disulfide. Application
      of 900 kHz ultrasound did not produce any noticeable change. When carbon
      disulfide was irradiated with 20 kHz, the liquid formed a heterogeneous mixture
      of black particles in a yellow solution. The rate of dissociation decreased with
      increasing temperature, in agreement with most sonochemical reactions. The rate
      also decreased with decreasing area of the horn tip, keeping total power
      constant. This dependence on the horn tip area, as well as that on the frequency,
      is in opposition to the dependence for the formation of iodine from the
      sonication of aqueous potassium iodide solution [See Part II, Ultrasonics
      Sonochemistry 3 (1996) 19]. The X-ray spectrum of the black particles and the
      yellow residue obtained after evaporation showed the presence of amorphous carbon
      and monoclinic sulfur. The rate of sono-dissociation of carbon disulfide in the
      presence of different gases is in the order He > H2 > Air > Ar > O2 > CO2.

PMID- 11233927
TI  - The effect of ultrasonic waves on the oxidation current of chlorpromazine in the
      38 and 96 kHz-ultrasonic vibrating electrode voltammetry.
AB  - In the case of 38 and 96 kHz ultrasonic vibrating electrode (USVE) voltammetry of
      chlorpromazine, the oxidation current increased considerably with ultrasonic
      power (amplitude). Movement of the first oxidation product, crimson coloured
      cation radical, and the streaming of liquid in the neighbourhood of the USVE,
      were visually observed in order to understand the mechanism of the promotive
      effects of ultrasound on the oxidation reaction. The reaction profile of the
      oxidation of chlorpromazine in 38 kHz seems to be somewhat different from that in
      96 kHz. However, the mechanical agitation of solution in the area nearest the
      electrode surface, which is essentially the same fundamental mechanism, takes
      place in both the cases of 38 and 96 kHz. Both micro- and macro-streamings due to
      the vibration of a small bubble on the electrode surface with a frequency lower
      than that of the ultrasonic wave were formed in 38 kHz. These streamings seemed
      to contribute to the agitation and the exchange of the solution near the
      electrode surface. However, at the same ultrasonic amplitude, the oxidation
      current at 96 kHz was much greater than that at 38 kHz. Such a promoting effect
      of ultrasound on the electrode reaction was considered to be due to the increase
      of the moving speed or to the acceleration of the particle in the solution.

PMID- 11233926
TI  - Ultrasound induced aqueous polycyclic aromatic hydrocarbon reactivity.
AB  - An investigation to determine the ability of ultrasonic radiation to chemically
      alter polycyclic aromatic hydrocarbons (PAHs) in aqueous solution has been
      conducted. The data indicate that chemical alteration of PAHs can be induced
      under intense ultrasonic treatment. The extent and outcome of reaction is a
      function of irridation time and aqueous solution parameters. Reaction products
      were analysed by gas chromatography (GC) and gas chromatography/mass spectrometry
      (GC/MS). Reaction products from ultrasonic treatment of aqueous solutions of
      biphenyl include ortho, meta, and para-1,1 biphenols. The principal product from
      ultrasonic treatment of aqueous phenanthrene solutions appears to be a
      phenanthrene-diol. The number and composition of reaction products for both PAHs
      tested suggest that a free radical mechanism is likely during aqueous high
      intensity ultrasonic treatment. The use of ultrasound to treat PAH contaminated
      aqueous solutions in tandem with other methodologies appears promising. However,
      the toxicity of reaction products produced by treatment remains to be determined.

PMID- 11233928
TI  - Sonophotoluminescence from aqueous and non-aqueous solutions.
AB  - The sonoluminescence generated in air-saturated aqueous and non-aqueous solutions
      using 515 kHz ultrasound has been used to vibronically excite several fluorescent
      solutes, namely fluorescein, eosin, pyranine and pyrene. Emission, referred to as
      'sonophotoluminescence', was generated in situ with emission spectra that closely
      matched those obtained by direct photoexcitation of the solutes by an external
      light source. In the case of pyranine, experiments were also conducted in the
      presence of the surfactant, sodium dodecyl sulphate (SDS). The presence of 1 mM
      SDS enhances the sonoluminescence and sonophotoluminescence signals above that
      seen in pure water by a factor of about 2. Pyrene sonophotoluminescence was
      observed in ethylene glycol. The emission was quenched by the addition of I-,
      providing good evidence that emission was from pyrene in bulk solution and not
      within, or on the surface of cavitation bubbles.

PMID- 11233929
TI  - Effects of ultrasound on the formation of alpha-benzoylbenzyl cyanide from benzyl
      cyanide and alkylphenyl ketone from alpha-alkylbenzyl cyanide by potassium
      superoxide in the presence of crown ether.
AB  - Ultrasound accelerates the formation of alpha-benzoylbenzyl cyanide and benzoic
      acid in the reaction of benzyl cyanide with potassium superoxide in the presence
      of 18-crown-6. Similarly, 4-methylbenzyl cyanide, 4-methoxybenzyl cyanide and 4
      chlorobenzyl cyanide gave the corresponding alpha-(4-methylbenzoyl)-4
      methylbenzyl cyanide, alpha-(4-methoxybenzoyl)-4-methoxybenzyl cyanide and alpha
      (4-chlorobenzoyl)-4-chlorobenzyl cyanide in 25-43% isolated yields under the same
      reaction conditions. Benzoic, p-toluic, 4-methoxybenzoic and 4-chlorobenzoic
      acids were also formed in these reactions. No reaction was observed when the
      mixture was simply stirred. Reflux instead of sonication gave lower yields of the
      products. However, alpha-alkylbenzyl cyanide produced a high yield of the
      phenylalkyl ketones when stirred. Interestingly, the corresponding benzoic acid
      was not formed in these reactions. Possible mechanisms for the formation of alpha
      benzoylbenzyl cyanide from benzyl cyanide and phenylalkyl ketones from alpha
      alkylbenzyl cyanide are also proposed.

PMID- 11233930
TI  - Ultrasonic depolymerization of the chitin-glucan complex from Aspergillus niger
      and antimutagenic activity of its product.
AB  - Sonication was effective for the depolymerization of carboxymethylated chitin
      glucan complex (CM-CG) isolated from the cell wall of Aspergillus niger. After 10
      min of sonication and subsequent gel filtration, two samples (CM-CG(I) and CM
      CG(II)) with significantly distinct molecular weights (660 kDa and 19 kDa,
      respectively) and different nitrogen contents (3.02 and 1.69%) were obtained. CM
      CG(II) with lower Mw was also effective against cyclophosphamide mutagenicity by
      oral administration in mice.

PMID- 11233931
TI  - Sonolysis of an aqueous mixture of trichloroethylene and chlorobenzene.
AB  - The effect of the initial concentration on the ultrasonic degradation of two
      volatile organic compounds trichloroethylene (TCE) and chlorobenzene (CB) was
      investigated. At higher concentrations, slower sonolysis rates were obtained due
      to the lowering of the average specific heat ratio gamma of the gas inside the
      cavitation bubbles. Furthermore, the effect of different concentrations of CB on
      the sonolysis of 3.34 mM TCE and the effect of different concentrations of TCE on
      the sonolysis of 3.44 mM CB was examined. The presence of CB lowered the
      sonolysis rate of TCE, while the sonolysis rate of CB did not decrease by TCE
      addition. An even higher sonolysis rate was obtained for 3.44 mM CB in the
      presence of 0.84 mM TCE than without TCE. The explanation for the different
      effects of both volatile organics on each other's sonolysis rate is thought to be
      the difference in reaction rate of TCE and CB with the radicals formed during
      sonolysis. The effect of TCE on the sonolysis rate of CB by lowering the gamma
      value is compensated by an increased indirect degradation of CB by radicals
      formed out of TCE. The decreased thermal degradation and the increased indirect
      radical degradation of CB in the presence of TCE is demonstrated by determining
      the kinetics of the degradation products styrene and dichlorobenzene.

PMID- 11233932
TI  - Sonochemical treatment of natural ground water at different high frequencies:
      preliminary results.
AB  - Naturally occurring ground water polluted by highly volatile chlorinated
      compounds, with 1,2-dichloroethane as the main contaminant, was sonicated with
      high frequency ultrasound (361, 620 and 1086 kHz) in order to investigate if
      results from studies performed with single model compounds in water can be
      applied to a natural ground water. It was shown that the treated highly volatile
      halogenated hydrocarbons are almost completely destroyed by ultrasound in natural
      ground water within 60 min. It also transpired that the naturally occurring
      inorganic components and gases in the ground water play an important role.

PMID- 11233933
TI  - Theory of local electrification of cavitation bubbles: new approaches.
AB  - The theory of local electrification of cavitation bubbles has been generalised.
      The major cases for a local electrification of bubbles in a cavitation field were
      considered; i.e., fragmentation and deformation of cavitation bubbles. The
      splitting of cavitation bubbles was considered taking into account surface
      tension, bubble perturbation, Stokes force and electrostatic forces between like
      charges on the wall of the collapsing neck of the fragment bubble. The problem of
      the uncompensated charge on the surface of the deformed cavitation bubble is
      solved. For this purpose radial deformations are considered in terms of the
      paraboloid of rotation and axial deformation approximated by one cavity
      hyperboloid of rotation. The maximum electric strength is accounted for. An
      explanation for some physical and physico-chemical effects in cavitation fields
      is proposed in terms of the electrical theory of the local electrification of
      cavitation bubbles.

PMID- 11233934
TI  - A mathematical treatment of the use of ultrasound in homogeneous and
      heterogeneous catalysis.
AB  - The possibility of increasing the effectiveness of a catalyst in the form of
      porous granules by artificially changing the activity profile of a catalytic
      reaction proceeding under non-steady-state conditions is shown. The results can
      also be used for the analysis of homogeneous reactions. Ultrasound can be used to
      generate the non-uniform concentration and temperature fields with time in the
      reaction mixture. Ultrasound can also be used for the activation and deactivation
      of the catalytic centres.

PMID- 11233935
TI  - Acoustic cavitation structures and simulations by a particle model.
AB  - Cavitation bubbles in acoustic resonators are observed to arrange in branch-like
      patterns. We give a brief review of the anatomy of such structures and outline an
      approach for simulation by individual, moving bubbles. This particle model can
      reproduce an experimentally observed transition between different structure types
      in a rectangular resonator cell.

PMID- 11233936
TI  - Modeling of three-dimensional pressure fields in sonochemical reactors with an
      inhomogeneous density distribution of cavitation bubbles. Comparison of
      theoretical and experimental results.
AB  - During the last 50 years extensive experimental investigation has been carried
      out on the chemical effects of ultrasound, but limited work has been reported on
      modeling. This paper presents a new model in which a numerical calculation of the
      three-dimensional linear sound pressure field distribution in a commonly used
      sonoreactor containing three transducers is carried out. In this model the
      inhomogeneous three-dimensional time-dependent wave equation was solved using the
      finite difference approach. The modeled results are then compared with the
      experimentally measured values, and the agreement, in general, is found to be
      good. Further, our modeling studies have an advantage, since they clearly
      describe the continuous sound pressure field structure, unlike previously
      reported results in which some information is missing due to limited intermittent
      measured points.

PMID- 11233937
TI  - Characterisation of the acoustic cavitation cloud by two laser techniques.
AB  - An experimental investigation of the size and volumetric concentration of
      acoustic cavitation bubbles is presented. The cavitation bubble cloud is
      generated at 20 kHz by an immersed horn in a rectangular glass vessel containing
      bi-distilled water. Two laser techniques, laser diffraction and phase Doppler
      interferometry, are implemented and compared. These two techniques are based on
      different measuring principles. The laser diffraction technique analyses the
      light pattern scattered by the bubbles along a line-of-sight of the experimental
      vessel (spatial average). The phase Doppler technique is based on the analysis of
      the light scattered from single bubbles passing through a set of interference
      fringes formed by the intersection of two laser beams: bubble size and velocity
      distributions are extracted from a great number of single-bubble events (local
      and temporal average) but only size distributions are discussed here.
      Difficulties arising in the application of the laser diffraction technique are
      discussed: in particular, the fact that the acoustic wave disturbs the light
      scattering patterns even when there are no cavitation bubbles along the
      measurement volume. As a consequence, a procedure has been developed to correct
      the raw data in order to get a significant bubble size distribution. After this
      data treatment has been applied the results from the two measurement techniques
      show good agreement. Under the emitter surface, the Sauter mean diameter D(3, 2)
      is approximately 10 microm by phase Doppler measurement and 7.5 microm by laser
      diffraction measurement at 179 W. Note that the mean measured diameter is much
      smaller than the resonance diameter predicted by the linear theory (about 280
      microm). The influence of the acoustic power is investigated. Axial and radial
      profiles of mean bubble diameters and void fraction are also presented.

PMID- 11233938
TI  - Hydrodynamic cavitation for sonochemical effects.
AB  - A comparative study of hydrodynamic and acoustic cavitation has been made on the
      basis of numerical solutions of the Rayleigh-Plesset equation. The bubble/cavity
      behaviour has been studied under both acoustic and hydrodynamic cavitation
      conditions. The effect of varying pressure fields on the collapse of the cavity
      (sinusoidal for acoustic and linear for hydrodynamic) and also on the latter's
      dynamic behaviour has been studied. The variations of parameters such as initial
      cavity size, intensity of the acoustic field and irradiation frequency in the
      case of acoustic cavitation, and initial cavity size, final recovery pressure and
      time for pressure recovery in the case of hydrodynamic cavitation, have been
      found to have significant effects on cavity/bubble dynamics. The simulations
      reveal that the bubble/cavity collapsing behaviour in the case of hydrodynamic
      cavitation is accompanied by a large number of pressure pulses of relatively
      smaller magnitude, compared with just one or two pulses under acoustic
      cavitation. It has been shown that hydrodynamic cavitation offers greater control
      over operating parameters and the resultant cavitation intensity. Finally, a
      brief summary of the experimental results on the oxidation of aqueous KI solution
      with a hydrodynamic cavitation set-up is given which supports the conclusion of
      this numerical study. The methodology presented allows one to manipulate and
      optimise of specific process, either physical or chemical.

PMID- 11233939
TI  - Influence of ultrasound on mixing on the molecular scale for water and viscous
      liquids.
AB  - Micromixing has a decisive action on the yield of fast reactions such as
      combustions, polymerizations, neutralizations and precipitations. The aim of this
      study was to test the possible effect of ultrasound on micromixing, through the
      phenomenon of acoustic cavitation. To evaluate the local state of micromixing, we
      used a system of parallel competing reactions involving the Dushman reaction
      between iodide and iodate, coupled with a neutralization. At first, we studied
      the effects of the acoustic frequency on micromixing (20-540-1000 kHz). It was
      found that micromixing through acoustic cavitation and acoustic streaming was
      more important at 20 kHz than at 540 kHz or 1 MHz. At high and low frequency, it
      was shown that the injection must be located near the ultrasonic emitter. The
      influence of the acoustic intensity proved to be predominant mostly for low
      intensities; for an acoustic intensity of 10 W cm(-2), a characteristic
      micromixing time of about 0.015 s has been obtained. Viscous media have been
      studied and experiments showed that micromixing is more difficult to achieve than
      in aqueous media, but that ultrasound may be as effective as classic stirring.

PMID- 11233940
TI  - Multibubble sonoluminescence in aqueous salt solutions.
AB  - The sonoluminescence from aqueous solutions containing various salts in the
      concentration range of 0 to 7 M has been examined using 3.5 ms pulses of 515 kHz
      ultrasound. In almost all cases the sonoluminescence intensity recorded increased
      with increasing salt level until a critical concentration (in the range of 1-2 M)
      was reached. At salt levels above the critical concentration the signal intensity
      decreased sharply with increasing salt concentration. It is not possible to
      satisfactorily account for the trends in terms of changes in solution viscosity,
      rate of bubble coalescence, water vapour pressure, air/water interfacial tension
      or ionic strength. However, a good correlation of the increase in the signal with
      the extent of gas solubilisation in the solutions with changing salt
      concentration was observed. Possible reasons for the signal increase with the
      addition of salts and the marked decrease at high salt concentrations are
      discussed.

PMID- 11233941
TI  - Emulsification by ultrasound: drop size distribution and stability.
AB  - The aim of this work is to compare the oil-in-water emulsions produced by
      mechanical agitation (Ultra-Turrax, 10,000 rpm, P = 170 W) or power ultrasound
      (ultrasound horn, 20 kHz, 130 W) using the same model system:
      water/kerosene/polyethoxylated (20 EO) sorbitan monostearate. The following
      parameters were varied: emulsification time, surfactant concentration, consumed
      power and volume fraction of oil. With ultrasound, the drop size (Sauter
      diameter, d32) is much smaller than that given by mechanical agitation under the
      same conditions, which makes insonated emulsions more stable. For a given drop
      size (d32), less surfactant is required.

PMID- 11233942
TI  - Ultrasonic acceleration of ester hydrolyses.
AB  - Kinetics of acid-catalyzed hydrolysis of ethyl acetate in 1M HCl solution was
      investigated without sonication and under ultrasound at 22 kHz. An average 6.2
      fold ultrasonic rate enhancement for the temperature range of 10-28 degrees C was
      found. This is a considerably greater acceleration than previously reported for
      ester hydrolyses. It was suggested that a significant part of the sonochemical
      effect on polar reactions may be due to temperature gradients in the cavitating
      medium.

PMID- 11233943
TI  - Bis(acetylacetonato) dioxomolybdenum(VI) catalysed rearrangement of methylbutynol
      in the presence of ultrasound.
AB  - The molybdenum (VI) catalysed rearrangement of methylbutynol was carried out
      under the influence of ultrasound (20 kHz). Surprisingly, 2-methylpropene
      (isobutene) was found as the main product. The formation of isobutene can be
      explained by rearrangement to prenal, oxidation to 3,3-dimethylacrylic acid and
      then decarboxylation. 3,3-Dimethylacrylic acid was decarboxylated in the presence
      of ultrasound and a catalyst; without a catalyst or without ultrasound (at 50
      degrees C) it remained unchanged.

PMID- 11233944
TI  - Sonochemical and photochemical reactions of bromotrichloromethane in the presence
      and absence of 1-alkene.
AB  - Comparison between sonolysis and photolysis of bromotrichloromethane in the
      presence and absence of 1-alkenes was performed to elucidate the characteristics
      of homogeneous sonochemistry. Results indicate that the photolysis of BrCCl3
      generates radicals in a homogeneous and dispersed state, while sonolysis
      generates them in a heterogeneous and localized state. In the photochemical
      reaction the BrCCl3-adduct was obtained over a wide range of mole fractions of
      BrCCl3, whereas in the sonochemical reaction the yield of the BrCCl3-adduct
      showed a sharp maximum in a range of high mole fractions of BrCCl3. This may be
      attributed to the large variation in surface tension.

PMID- 11233945
TI  - Ultrasonics in heterogeneous metal catalysis: sonochemical chemo- and
      enantioselective hydrogenations over supported platinum catalysts.
AB  - Sonochemical chemo- and enantioselective hydrogenations over supported platinum
      catalysts are described. We disclose our results with respect to a sonochemical
      modification of the chemoselective hydrogenation of cinnamaldehyde over supported
      platinum catalysts, and the asymmetric hydrogenation of ethyl pyruvate promoted
      by various ultrasonic pretreatments. The ultrasonic pretreatment of the supported
      platinum catalysts was found to be highly beneficial in almost every case,
      improving both the catalytic activity and selectivity. The effect of additional
      experimental variables, such as hydrogen pressure, catalyst support, temperature
      and the ultrasonic insonation time were also studied. The enantioselectivity of
      the hydrogenation of ethyl pyruvate increased up to 97.1% ee. In the case of
      cinnamaldehyde hydrogenation, the selective preparation of cinnamyl alcohol
      became possible. The theoretical aspects of the working mechanisms in comparison
      with 'silent' reactions will also be provided.

PMID- 11233946
TI  - Supraventricular tachycardia.
AB  - Supraventricular tachycardias (SVT) comprise those tachycardias that originate
      above the bifurcation of the bundle of His. They can be classified broadly as AV
      node dependent and AV node independent. The mechanism and clinical manifestation
      of SVTs, which is essential to their correct diagnosis, is reviewed. The
      therapeutic management of SVTs, including acute and chronic drug therapy and
      catheter ablation, is discussed also.

PMID- 11233947
TI  - Evaluation and management of atrial fibrillation.
AB  - Atrial fibrillation is a common cardiac arrhythmia with significant sequela. The
      goals of treating atrial fibrillation are rate control, prevention of
      thromboembolism, and maintenance of sinus rhythm. The epidemiology and
      pathophysiology of atrial fibrillation is reviewed, as well as strategies and
      recommendations for achieving therapeutic goals. The authors also review
      investigational therapeutic options using nonpharmacologic modalities.

PMID- 11233948
TI  - Wide QRS complex tachycardias.
AB  - Wide QRS complex tachycardia is a common clinical occurrence and presents a
      diagnostic challenge for the physician. History, physical examination, chest
      radiographs, and electrocardiographic analysis are important in making the
      correct diagnosis. Diagnosis of ventricular tachycardia is supported by history
      of prior myocardial infarction or congestive heart failure, physical examination
      showing cannon A-waves in the jugular venous pulsation or variable heart sounds,
      chest radiograph showing cardiomegaly or evidence of prior cardiac surgery, and
      characteristic ECG features: AV dissociation, fusion/capture beats, QRS
      concordance or typical morphologic features in leads V1 and V6. In this article,
      a clinical approach to wide QRS complex tachycardias is presented.

PMID- 11233949
TI  - Ventricular tachycardia syndromes.
AB  - Better understanding of the underlying mechanism and substrate of different VTs
      has made it possible to tailor treatment strategies properly. The advent of
      sophisticated device-based therapy and of more precise and effective catheter
      ablation approaches will expand clinicians' ability to gain control of this
      multifaceted arrhythmia syndrome.

PMID- 11233950
TI  - Nonsustained ventricular tachycardia. A guide to the clinical significance and
      management.
AB  - The patient with nonsustained ventricular tachycardia represents a common
      management problem for the cardiologists and internists. Treatment is sometimes
      needed for the suppression of symptoms. More commonly, nonsustained ventricular
      tachycardia is asymptomatic, and the clinician must determine the prognostic
      importance. The prognostic implications, the role of electrophysiologic study,
      and the potential role of pharmacologic and defibrillator intervention depend on
      the underlying cardiac substrate present in the individual patient.

PMID- 11233951
TI  - Polymorphic ventricular tachycardia, long Q-T syndrome, and torsades de pointes.
AB  - PMVT is an uncommon arrhythmia with multiple causes. Classification and
      management are based on the Q-T interval. Torsades de pointes denotes PMVT in the
      setting of a prolonged Q-T interval and usually is iatrogenic in origin, although
      congenital LQTS is being recognized more frequently. Therapy of PMVT focuses on
      the establishment of hemodynamic stability, the removal or correction of
      precipitants, and the acute and long-term inhibition of subsequent episodes.
      Evaluation of these patients should include a thorough history and physical
      examination and an assessment for underlying heart disease and known [figure: see
      text] eliciting factors. Long-term management must be tailored to the individual
      and the underlying cause and should be conducted by an experienced cardiac
      electrophysiologist.

PMID- 11233952
TI  - Implantable cardiac defibrillators.
AB  - The implantable cardioverter defibrillator (ICD) represents an important
      development in the effort to reduce the incidence of sudden cardiac death (almost
      400,000 yearly in the United States). Early generation ICDs, which required
      epicardial lead systems and abdominal placement of the pulse generator, have been
      replaced by transvenous leads and pectoral implants. Other important refinements,
      which include biphasic waveforms, extensive memory capability, antitachycardia
      pacing, and enhanced sensing algorithms, have greatly improved patient tolerance.
      Ongoing trials and those in the planning stages will continue to expand the
      indications for ICDs and will focus on cost-effectiveness.

PMID- 11233953
TI  - Cardiac pacing. A review.
AB  - Pacing is a field of rapid clinical progress and technologic advances. Clinical
      progress in the 1990s included the refinement of indications for pacing as well
      as the use of pacemakers for new, nonbradycardiac indications, such as the
      treatment of cardiomyopathies and CHF and the prevention of atrial fibrillation.
      Important published data and studies in progress are shedding new light on issues
      of pacing mode selection, and they may influence future practice significantly.
      Important technologic advances include development of new rate-adaptive sensors
      and sensor combinations and the evolution of pacemakers into sophisticated
      diagnostic devices with the capability to store data and ECGs. Automatic
      algorithms monitor the patient for appropriate capture, sensing, battery status,
      and lead impedance, providing better patient safety and pacemaker longevity.

PMID- 11233954
TI  - Diagnostic evaluation and management of patients with syncope.
AB  - This article focuses on the evaluation of patients with syncope, a symptom not a
      disease. Syncope is a transient loss of consciousness associated with loss of
      postural tone with spontaneous recovery. The authors discuss the utility of an
      indications for different diagnostic tests, the indications for hospital
      admission, and the management of patients with certain known causes of syncope,
      including vasovagal and arrhythmic.

PMID- 11233955
TI  - Syncope resulting from autonomic insufficiency syndromes associated with
      orthostatic intolerance.
AB  - The disorders of autonomic control associated with orthostatic intolerance are a
      diverse group that can result in syncope and near-syncope. A basic understanding
      of these disorders is essential to diagnosis and proper treatment. Ongoing
      studies should help to define better the spectrum of these disorders and to
      elaborate better diagnostic and treatment modalities.

PMID- 11233956
TI  - Catheter ablation for cardiac arrhythmias.
AB  - The safety and efficacy of catheter ablation for treatment of most types of
      cardiac arrhythmias are well established. These arrhythmias and arrhythmia
      substrates include AVNRT, accessory pathways, focal atrial tachycardia, atrial
      flutter, idiopathic ventricular tachycardia, and bundle-branch re-entry. Catheter
      ablation is considered as an alternative to pharmacologic therapy in the
      treatment of these cardiac arrhythmias.

PMID- 11233957
TI  - Proarrhythmia.
AB  - Proarrhythmia is defined as the aggravation of an existing arrhythmia or the
      development of a new arrhythmia secondary to antiarrhythmic drug. Proarrhythmic
      events include drug-induced bradyarrhythmias, atrial and ventricular
      proarrhythmias. New onset sustained or incessant ventricular tachycardia and
      torsade de pointes can be life threatening. This article reviews the incidence,
      aggravating factors, and treatment of proarrhythmia.

PMID- 11233958
TI  - Evaluation and management of cardiac arrhythmias in the elderly.
AB  - Cardiac arrhythmias are common in elderly patients. Complete evaluation with
      detection of underlying structural heart disease and comorbidities is necessary.
      Prognosis is dependent on the presence of underlying heart disease, particularly
      the degree of ventricular dysfunction and the presence of comorbidities. Long
      term prognosis is excellent in patients without underlying heart disease or
      severe comorbidities. Management and specific drug therapy in elderly patients
      with arrhythmias need to be individualized in reference to the underlying cardiac
      disorder, drug side effects, and the patient's comorbidities.

PMID- 11233973
TI  - An early transition state for folding of the P4-P6 RNA domain.
AB  - Tertiary folding of the 160-nt P4-P6 domain of the Tetrahymena group I intron RNA
      involves burying of substantial surface area, providing a model for the folding
      of other large RNA domains involved in catalysis. Stopped-flow fluorescence was
      used to monitor the Mg2+-induced tertiary folding of pyrene-labeled P4-P6. At 35
      degrees C with [Mg2+] approximately 10 mM, P4-P6 folds on the tens of
      milliseconds timescale with k(obs) = 15-31 s(-1). From these values, an
      activation free energy deltaG(double dagger) of approximately 8-16 kcal/mol is
      calculated, where the large range for deltaG(double dagger) arises from
      uncertainty in the pre-exponential factor relating k(obs) and delta G(double
      dagger). The folding rates of six mutant P4-P6 RNAs were measured and found to be
      similar to that of the wild-type RNA, in spite of significant thermodynamic
      destabilization or stabilization. The ratios of the kinetic and thermodynamic
      free energy changes phi = delta deltaG(double dagger)/delta deltaG(o') are
      approximately 0, implying a folding transition state in which most of the native
      state tertiary contacts are not yet formed (an early folding transition state).
      The k(obs) depends on the Mg2+ concentration, and the initial slope of k(obs)
      versus [Mg2+] suggests that only approximately 1 Mg2+ ion is bound in the rate
      limiting folding step. This is consistent with an early folding transition state,
      because folded P4-P6 binds many Mg2+ ions. The observation of a substantial
      deltaG(double dagger) despite an early folding transition state suggests that a
      simple two-state folding diagram for Mg2+-induced P4-P6 folding is incomplete.
      Our kinetic data are some of the first to provide quantitative values for an
      activation barrier and location of a transition state for tertiary folding of an
      RNA domain.

PMID- 11233974
TI  - Identification of candidate mitochondrial RNA editing ligases from Trypanosoma
      brucei.
AB  - Most mitochondrial genes of Trypanosoma brucei do not contain the necessary
      information to make translatable mRNAs. These transcripts must undergo RNA
      editing, a posttranscriptional process by which uridine residues are added and
      deleted from mitochondrial mRNAs. RNA editing is believed to be catalyzed by a
      ribonucleoprotein complex containing endonucleolytic, terminal uridylyl
      transferase (TUTase), 3' uridine-specific exonucleolytic (U-exo), and ligase
      activities. None of the catalytic enzymes for RNA editing have been identified.
      Here we describe the identification of two candidate RNA ligases (48 and 52 kDa)
      that are core catalytic components of the T. brucei ribonucleoprotein editing
      complex. Both enzymes share homology to the covalent nucleotidyl transferase
      superfamily and contain five key signature motifs, including the active site
      KXXG. In this report, we present data on the proposed 48 kDa RNA editing ligase.
      We have prepared polyclonal antibodies against recombinant 48 kDa ligase that
      specifically recognize the trypanosome enzyme. When expressed in trypanosomes as
      an epitope-tagged fusion protein, the recombinant ligase localizes to the
      mitochondrion, associates with RNA editing complexes, and adenylates with ATP.
      These findings provide strong support for the enzymatic cascade model for
      kinetoplastid RNA editing.

PMID- 11233975
TI  - Interplay between AAUAAA and the trans-splice site in processing of a
      Caenorhabditis elegans operon pre-mRNA.
AB  - About half of Caenorhabditis elegans genes have a 1-2 bp mismatch to the
      canonical AAUAAA hexamer that signals 3' end formation. One rare variant, AGUAAA,
      is found at the 3' end of the mai-1 gene, the first gene in an operon also
      containing gpd-2 and gpd-3. When we expressed this operon under heat shock
      control, 3' end formation dependent on the AGUAAA was very inefficient, but could
      be rescued by a single bp change to create a perfect AAUAAA. When AGUAAA was
      present, most 3' ends formed at a different site, 100 bp farther downstream,
      right at the gpd-2 trans-splice site. Surprisingly, 3' end formation at this site
      did not require any observable match to the AAUAAA consensus. It is possible that
      3' end formation at this site occurs by a novel mechanism--trans-splicing
      dependent cleavage--as deletion of the trans-splice site prevented 3' end
      formation here. Changing the AGUAAA to AAUAAA also influenced the trans-splicing
      process: with AGUAAA, most of the gpd-2 product was trans-spliced to SL1, rather
      than SL2, which is normally used at downstream operon trans-splice sites.
      However, with AAUAAA, SL2 trans-splicing of gpd-2 was increased. Our results
      imply that (1) the AAUAAA consensus controls 3' end formation frequency in C.
      elegans; (2) the AAUAAA is important in determining SL2 trans-splicing events
      more than 100 bp downstream; and (3) in some circumstances, 3' end formation may
      occur by a trans-splicing-dependent mechanism.

PMID- 11233976
TI  - The 100-kda U5 snRNP protein (hPrp28p) contacts the 5' splice site through its
      ATPase site.
AB  - To identify splicing factors in proximity of the 5' splice site (5'SS), we
      followed a crosslinking profile of site-specifically modified, photoreactive RNA
      substrates. Upon U4/U5/U6 snRNP addition, the 5'SS RNA crosslinks in an ATP
      dependent manner to U6 snRNA, an unidentified protein p27, and the 100-kDa U5
      snRNP protein, a human ortholog of an ATPase/RNA helicase yPrp28p. The
      5'SS:hPrp28p crosslink maps to the highly conserved TAT motif in proximity of the
      ATP-binding site in hPrp28p. We propose that hPrp28p acts as a helicase to unwind
      the 5'SS:U1 snRNA duplex, and at the same time as a 5'SS translocase, which, upon
      NTP-dependent conformational change, positions the 5'SS for pairing with U6 snRNA
      within the spliceosome. This repositioning of the 5'SS takes place regardless of
      whether the 5'SS is originally duplexed with U1 snRNA.

PMID- 11233977
TI  - Mechanism of ribosome recruitment by hepatitis C IRES RNA.
AB  - Many viruses and certain cellular mRNAs initiate protein synthesis from a highly
      structured RNA sequence in the 5' untranslated region, called the internal
      ribosome entry site (IRES). In hepatitis C virus (HCV), the IRES RNA functionally
      replaces several large initiation factor proteins by directly recruiting the 43S
      particle. Using quantitative binding assays, modification interference of
      binding, and chemical and enzymatic footprinting experiments, we show that three
      independently folded tertiary structural domains in the IRES RNA make intimate
      contacts to two purified components of the 43S particle: the 40S ribosomal
      subunit and eukaryotic initiation factor 3 (eIF3). We measure the affinity and
      demonstrate the specificity of these interactions for the first time and show
      that the high affinity interaction of IRES RNA with the 40S subunit drives
      formation of the IRES RNA-40S-eIF3 ternary complex. Thus, the HCV IRES RNA
      recruits 43S particles in a mode distinct from both eukaryotic cap-dependent and
      prokaryotic ribosome recruitment strategies, and is architecturally and
      functionally unique from other large folded RNAs that have been characterized to
      date.

PMID- 11233978
TI  - snoRNA nuclear import and potential for cotranscriptional function in pre-rRNA
      processing.
AB  - Several snoRNAs are essential for the sequence of cleavage events required to
      produce the mature forms of 18S, 5.8S, and 28S rRNA from the large precursor
      molecule. In the absence of U22, mature 18S rRNA fails to accumulate; U8 snoRNA
      is essential for accumulation of both 5.8S and 28S rRNA. The mechanisms by which
      snoRNAs facilitate these cleavage events is not known and might include direct
      cleavage or assisting the rate or efficiency of ribosome assembly. To learn more
      about the mechanisms of snoRNA-mediated pre-rRNA processing, an examination of
      the kinetics of pre-rRNA processing in Xenopus oocytes was undertaken. Correct
      pre-rRNA processing can be restored in snoRNA-depleted oocytes following
      cytoplasmic injection of the corresponding in vitro-synthesized snoRNA. Analysis
      of the kinetics of pre-rRNA processing in these snoRNA-rescue experiments
      demonstrated that the rate of accumulation of mature rRNAs was slower than that
      seen in untreated oocytes. The snoRNAs were imported into the nucleus at a rate
      and overall efficiency less than that of U1 snRNA, used as a control for import.
      However, sufficient levels of snoRNA were present in the nucleus to yield a
      functional phenotype (rescue of rRNA processing) several hours before the snoRNAs
      were directly detectable in the nucleus via autoradiography. This indicated that
      very low amounts of the snoRNA in the nucleus were sufficient for rescue.
      Finally, transcriptional inhibitors were used to separate transcription and
      processing. Failure to rescue snoRNA-mediated processing of pre-accumulated
      precursors is consistent with a scenario in which U8 and U22 must be present
      during transcription of pre-rRNA.

PMID- 11233979
TI  - New insight into RNase P RNA structure from comparative analysis of the archaeal
      RNA.
AB  - A detailed comparative analysis of archaeal RNase P RNA structure and a
      comparison of the resulting structural information with that of the bacterial RNA
      reveals that the archaeal RNase P RNAs are strikingly similar to those of
      Bacteria. The differences between the secondary structure models of archaeal and
      bacterial RNase P RNA have largely disappeared, and even variation in the
      sequence and structure of the RNAs are similar in extent and type. The structure
      of the cruciform (P7-11) has been reevaluated on the basis of a total of 321
      bacterial and archaeal sequences, leading to a model for the structure of this
      region of the RNA that includes an extension to P11 that consistently organizes
      the cruciform and adjacent highly-conserved sequences.

PMID- 11233980
TI  - The Bacillus subtilis RNase P holoenzyme contains two RNase P RNA and two RNase P
      protein subunits.
AB  - Ribonuclease P (RNase P) catalyzes the 5' maturation of precursor tRNA
      transcripts and, in bacteria, is composed of a catalytic RNA and a protein. We
      investigated the oligomerization state and the shape of the RNA alone and the
      holoenzyme of Bacillus subtilis RNase P in the absence of substrate by
      synchrotron small-angle X-ray scattering and affinity retention. The B. subtilis
      RNase P RNA alone is a monomer; however, the scattering profile changes upon the
      addition of monovalent ions, possibly suggesting different interdomain angles. To
      our surprise, the X-ray scattering data combined with the affinity retention
      results indicate that the holoenzyme contains two RNase P RNA and two RNase P
      protein molecules. We propose a structural model of the holoenzyme with a
      symmetrical arrangement of the two RNA subunits, consistent with the X-ray
      scattering results. This (P RNA)2(P protein)2 complex likely binds substrate
      differently than the conventional (P RNA)1(P protein)1 complex; therefore, the
      function of the B. subtilis RNase P holoenzyme may be more diverse than
      previously thought. These revisions to our knowledge of the RNase P holoenzyme
      suggest a more versatile role for proteins in ribonucleoprotein complexes.

PMID- 11233981
TI  - Identification of the gene encoding the 5S ribosomal RNA maturase in Bacillus
      subtilis: mature 5S rRNA is dispensable for ribosome function.
AB  - Over 25 years ago, Pace and coworkers described an activity called RNase M5 in
      Bacillus subtilis cell extracts responsible for 5S ribosomal RNA maturation
      (Sogin & Pace, Nature, 1974, 252:598-600). Here we show that RNase M5 is encoded
      by a gene of previously unknown function that is highly conserved among the low G
      + C gram-positive bacteria. We propose that the gene be named rnmV. The rnmV gene
      is nonessential. B. subtilis strains lacking RNase M5 do not make mature 5S rRNA,
      indicating that this process is not necessary for ribosome function. 5S rRNA
      precursors can, however, be found in both free and translating ribosomes. In
      contrast to RNase E, which cleaves the Escherichia coli 5S precursor in a single
      stranded region, which is then trimmed to yield mature 5S RNA, RNase M5 cleaves
      the B. subtilis equivalent in a double-stranded region to yield mature 5S rRNA in
      one step. For the most part, eubacteria contain one or the other system for 5S
      rRNA production, with an imperfect division along gram-negative and gram-positive
      lines. A potential correlation between the presence of RNase E or RNase M5 and
      the single- or double-stranded nature of the predicted cleavage sites is
      explored.

PMID- 11233982
TI  - Design of multistable RNA molecules.
AB  - We show that the problem of designing RNA sequences that can fold into multiple
      stable secondary structures can be transformed into a combinatorial optimization
      problem that can be solved by means of simple heuristics. Hence it is feasible to
      design RNA switches with prescribed structural alternatives. We discuss the
      theoretical background and present an efficient tool that allows the design of
      various types of switches. We argue that both the general properties of the
      sequence structure map of RNA secondary structures and the ease with which our
      design tool finds bistable RNAs strongly indicates that RNA switches are easily
      accessible in evolution. Thus conformational switches are yet another function
      for which RNA can be employed.

PMID- 11233983
TI  - A tertiary structure model of the internal ribosome entry site (IRES) for
      methionine-independent initiation of translation.
AB  - Cricket paralysis-like viruses have a dicistronic positive-strand RNA genome.
      These viruses produce capsid proteins through internal ribosome entry site (IRES)
      mediated translation. The IRES element of one of these viruses, Plautia stall
      intestine virus (PSIV), forms a pseudoknot immediately upstream from the capsid
      coding sequence, and initiates translation from other than methionine.
      Previously, we estimated that the IRES element of PSIV consists of seven stem
      loops using the program MFOLD; however, experimental evidence of the predicted
      structures was not shown, except for stem-loop VI, which was responsible for
      formation of the pseudoknot. To determine the whole structure of the PSIV-IRES
      element, we introduced compensatory mutations into the upstream MFOLD-predicted
      helical segments. Mutation analysis showed that stem-loop V exists as predicted,
      but stem-loop IV is shorter than predicted. The structure of stem-loop III is
      different from predicted, and stem-loops I and II are not necessary for IRES
      activity. In addition, we identified two new pseudoknots in the IRES element of
      PSIV. The complementary sequence segments that are responsible for formation of
      the two pseudoknots are also observed in cricket paralysis virus (CrPV) and CrPV
      like viruses such as Drosophila C virus (DCV), Rhopalosiphum padi virus (RhPV),
      himetobi P virus (HiPV), Triatoma virus (TrV), and black queen-cell virus (BQCV),
      although each sequence is distinct in each virus. Considering the three
      pseudoknots, we constructed a tertiary structure model of the PSIV-IRES element.
      This structural model is applicable to other CrPV-like viruses, indicating that
      other CrPV-like viruses can also initiate translation from other than methionine.

PMID- 11233985
TI  - Complete 5' and 3' end maturation of group II intron-containing tRNA precursors.
AB  - Higher plant chloroplasts provide the only experimentally validated example of
      functional tRNA genes that are disrupted by group II introns. Here, precursor
      transcripts for tRNA(Gly)(UCC), tRNA(Val)(UAC), and tRNA(Ala)(UGC) were
      investigated for processing of 5' leader and 3' trailer sequences in vivo. Use of
      intron-specific primer pairs and inclusion of a barley chloroplast splicing
      mutant specifically allowed us to evaluate the potential effect of intervening
      sequences that disrupt tRNA secondary and tertiary structures. The data suggest
      that (1) neither integrity of the dihydrouridine nor the anticodon domain is
      required for the nucleotidyltransferase-mediated addition of 3'-terminal CCA; (2)
      interruption of these two structural elements by group II introns does not
      interfere with nucleotide-specific 5' maturation by RNase P; (3) processing
      intermediates of chloroplast tRNAs can be 3' polyadenylated; and (4) plastid DNA
      encoded proteins are not required for 3' and 5' maturation of plastid tRNAs.

PMID- 11233984
TI  - Programmed +1 frameshifting stimulated by complementarity between a downstream
      mRNA sequence and an error-correcting region of rRNA.
AB  - Like most retroviruses and retrotransposons, the retrotransposon Ty3 expresses
      its pol gene analog (POL3) as a translational fusion to the upstream gag analog
      (GAG3). The Gag3-Pol3 fusion occurs by frameshifting during translation of the
      mRNA that encodes the two separate but overlapping ORFs. We showed previously
      that the shift occurs by out-of-frame binding of a normal aminoacyl-tRNA in the
      ribosomal A site caused by an aberrant codonoanticodon interaction in the P site.
      This event is unlike all previously described programmed translational
      frameshifts because it does not require tRNA slippage between cognate or near
      cognate codons in the mRNA. A sequence of 15 nt distal to the frameshift site
      stimulates frameshifting 7.5-fold. Here we show that the Ty3 stimulator acts as
      an unstructured region to stimulate frameshifting. Its function depends on strict
      spacing from the site of frameshifting. Finally, the stimulator increases
      frameshifting dependent on sense codon-induced pausing, but has no effect on
      frameshifting dependent on pauses induced by nonsense codons. Complementarity
      between the stimulator and a portion of the accuracy center of the ribosome,
      Helix 18, implies that the stimulator may directly disrupt error correction by
      the ribosome.

PMID- 11233986
TI  - Important role of the tetraloop region of 4.5S RNA in SRP binding to its receptor
      FtsY.
AB  - Binding of Escherichia coli signal recognition particle (SRP) to its receptor,
      FtsY, requires the presence of 4.5S RNA, although FtsY alone does not interact
      with 4.5S RNA. In this study, we report that the exchange of the GGAA tetraloop
      sequence in domain IV of 4.5S RNA for UUCG abolishes SRP-FtsY interaction, as
      determined by gel retardation and membrane targeting experiments, whereas
      replacements with other GNRA-type tetraloops have no effect. A number of other
      base exchanges in the tetraloop sequence have minor or intermediate inhibitory
      effects. Base pair disruptions in the stem adjacent to the tetraloop or
      replacement of the closing C-G base pair with G-C partially restored function of
      the otherwise inactive UUCG mutant. Chemical probing by hydroxyl radical cleavage
      of 4.5S RNA variants show that replacing GGAA with UUCG in the tetraloop sequence
      leads to structural changes both within the tetraloop and in the adjacent stem;
      the latter change is reversed upon reverting the C-G closing base pair to G-C.
      These results show that the SRP-FtsY interaction is strongly influenced by the
      structure of the tetraloop region of SRP RNA, in particular the tetraloop stem,
      and suggest that both SRP RNA and Ffh undergo mutual structural adaptation to
      form SRP that is functional in the interaction with the receptor, FtsY.

PMID- 11233989
TI  - Alterations in cerebral diazepam binding inhibitor expression in drug dependence:
      a possible biochemical alteration common to drug dependence.
AB  - Mechanisms for formation of drug dependence and expression of withdrawal syndrome
      have not fully clarified despite of huge accumulation of experimental and
      clinical data at present. Several clinical features of withdrawal syndrome are
      considered to be common among patients with drug dependence induced by different
      drugs of abuse. One of them is anxiety. Recent investigations have revealed that
      diazepam binding inhibitor (DBI), a peptide consisting of 87 amino acids with
      molecular weight of about 10 kDa, serves as an inverse agonist for benzodiazepine
      (BZD) receptors with endogenously anxiogenic potential. These lines of data
      suggest that cerebral DBI expression in brain may participates in formation of
      drug dependence and/or emergence of withdrawal syndrome. Based on this working
      hypothesis, we have examined DBI expression in the brain derived from mice
      depended on alcohol (ethanol), nicotine, and morphine to investigate functional
      relationship between cerebral DBI expression and drug dependence. Cerebral DBI
      expression significantly increases in animals with drug dependence induced by
      these drugs, and in the cases of nicotine- and morphine-dependent mice
      concomitant administration of antagonists for nicotinic acetylcholine and opioid
      receptors, respectively, abolished the increase. Abrupt cessation of
      administration of drugs facilitated further increase in DBI expression.
      Therefore, these alterations in DBI expression have close relationship with
      formation of drug dependence and/or emergence of withdrawal syndrome, and are
      considered to be a common biochemical process in drug dependence induced by
      different drugs of abuse. Finding and elucidation of mechanisms for common
      biochemical alterations among drug dependence may provide a clue to clarify
      mechanisms for formation of drug dependence and/or emergence of withdrawal
      syndrome.

PMID- 11233987
TI  - Phosphorylation by Sky1p promotes Npl3p shuttling and mRNA dissociation.
AB  - Mammalian SR proteins are currently thought to function in mRNA export as well as
      splicing. They contain multiple phosphorylated serine/arginine (RS/SR)
      dipeptides. Although SR domains can be phosphorylated by many kinases in vitro,
      the physiologically relevant kinase(s), and the role(s) of these modifications in
      vivo have remained unclear. Npl3 is a shuttling protein in budding yeast that we
      showed previously to be a substrate for the mammalian SR protein kinase, SRPK1,
      as well as the related yeast kinase, Sky1. Here we demonstrate that Sky1p
      phosphorylates only one of Npl3p's eight SR/RS dipeptides. Mutation of the C
      terminal RS to RA, or deletion of SKY1, results in the cytoplasmic accumulation
      of Npl3p. The redistribution of Npl3p is accompanied by its increased association
      with poly(A)+ RNA and decreased association with its import receptor, Mtr10p, in
      vivo. We propose that phosphorylation of Npl3p by the cytoplasmically localized
      Sky1p is required for efficient release of mRNA upon termination of export.

PMID- 11233988
TI  - Mapping of RNA accessible sites by extension of random oligonucleotide libraries
      with reverse transcriptase.
AB  - A rapid and simple method for determining accessible sites in RNA that is
      independent of the length of target RNA and does not require RNA labeling is
      described. In this method, target RNA is allowed to hybridize with sequence
      randomized libraries of DNA oligonucleotides linked to a common tag sequence at
      their 5'-end. Annealed oligonucleotides are extended with reverse transcriptase
      and the extended products are then amplified by using PCR with a primer
      corresponding to the tag sequence and a second primer specific to the target RNA
      sequence. We used the combination of both the lengths of the RT-PCR products and
      the location of the binding site of the RNA-specific primer to determine which
      regions of the RNA molecules were RNA extendible sites, that is, sites available
      for oligonucleotide binding and extension. We then employed this reverse
      transcription with the random oligonucleotide libraries (RT-ROL) method to
      determine the accessible sites on four mRNA targets, human activated ras (ha
      ras), human intercellular adhesion molecule-1 (ICAM-1), rabbit beta-globin, and
      human interferon-gamma (IFN-gamma). Our results were concordant with those of
      other researchers who had used RNase H cleavage or hybridization with arrays of
      oligonucleotides to identify accessible sites on some of these targets. Further,
      we found good correlation between sites when we compared the location of
      extendible sites identified by RT-ROL with hybridization sites of effective
      antisense oligonucleotides on ICAM-1 mRNA in antisense inhibition studies.
      Finally, we discuss the relationship between RNA extendible sites and RNA
      accessibility.

PMID- 11233991
TI  - 2-Naphthylamine, a compound found in cigarette smoke, decreases both monoamine
      oxidase A and B catalytic activity.
AB  - Cigarette smokers exhibit a lower monoamine oxidase (MAO; EC 1.4.3.4) activity
      than nonsmokers. MAO is located in the outer membrane of mitochondria and exists
      as two isoenzymes, MAO A and B. MAO A prefers 5-hydroxytryptamine (serotonin),
      and MAO B prefers phenylethylamine (PEA) as substrate. Dopamine is a substrate
      for both forms. 2-Naphthylamine is a carcinogen found in high concentrations in
      cigarette smoke. The results of this study show that 2-naphthylamine has the
      ability to inhibit mouse brain MAO A and B in vitro by mixed type inhibition
      (competitive and non-competitive). The Ki for MAO A was determined to be 52.0
      microM and for MAO B 40.2 microM. The inhibitory effect of 2-naphthylamine on
      both MAO A and B catalytic activity, supports the hypothesis that smoking
      decreases MAO activity in vivo, instead that smokers with lower MAO activity are
      more prone to become a smoker.

PMID- 11233990
TI  - Carbon-11 labelled cholecystokininB antagonists: radiosynthesis and evaluation in
      rats.
AB  - Three cholecystokinin type B (CCKB) receptor antagonists were labelled with 11C
      and evaluated ex vivo in rat biodistribution studies. The CCKB antagonists were
      YF 476 and two other compounds of the basic 3-ureido-1,4-benzodiazepine class.
      Following tail-vein administration of [11C]-YF 476 exceedingly low levels of
      radioactivity were found in all brain regions from 5 to 60 min post-injection.
      Similar results were obtained using the other two 11C-labelled CCKB antagonists.
      In light of the very poor brain penetration of these compounds, reports on the
      central nervous system activity of this class of CCKB antagonists should be
      viewed with caution.

PMID- 11233992
TI  - Effects of vasoactive intestinal peptide (VIP) and somatostatin (SST) on
      lipoprotein receptor expression by A431 tumor cells.
AB  - A variety of tumor cells have been shown to express lipoprotein receptors. Recent
      data suggest that lipoprotein receptors may play a regulatory role in the growth
      of certain tumor cells. We investigated the effects of vasoactive intestinal
      peptide (VIP) and somatostatin-14 (SST-14) on the binding of 111Indium-labeled
      lipoproteins [(111)In-low density lipoprotein ((111)In-LDL), (111)In-high density
      lipoprotein ((111)In-HDL) and (111)In-very low density lipoprotein ((111)In
      VLDL)] onto the epidermoid mammary carcinoma cell line A431. Scatchard analyses
      of the binding data indicated one class of specific high affinity binding sites
      for LDL, HDL and VLDL expressed by A431 cells, respectively. VIP increased
      significantly the binding capacity for (111)In-LDL on A431 cells. The VIP-induced
      increase of (111)In-LDL binding sites was inhibited by SST-14. Furthermore, SST
      14 inhibited VIP-induced 3H-thymidine incorporation and adenosine 3'-5' cyclic
      monophosphate (cAMP) formation in A431 cells with IC50 values in the range of 5-7
      nM. However, SST-14 showed no effect on dibutyryl-cAMP-induced increase of
      (111)In-LDL binding sites expressed on A431 cells. In contrast to (111)In-LDL
      binding, no effects of VIP or SST-14 on HDL or VLDL binding to A431 tumor cells
      were found. Our results suggest a direct effect of VIP and SST-14 on LDL-binding
      onto tumor cells. The complex interactions between VIP and SST-14 on LDL receptor
      expression of tumor cells may play a role in tumor cell lipid metabolism.

PMID- 11233994
TI  - Immune reponses in human mesangial cells regulated by emodin from Polygonum
      hypoleucum Ohwi.
AB  - In the hope of identifying agents of therapeutic value in glomerulonephritis from
      Chinese herbs, we found that methanolic extracts of Polygonum hypoleucum Ohwi (P.
      hypoleucum Ohwi) inhibit human mesangial cells proliferation activated with
      interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) previously. This study was
      designed to identify bioactive components from P. hypoleucum Ohwi and elucidate
      their action mechanisms. We tested four anthraquinones emodin, emodin 1-O-beta-D
      glucoside (49A), physcion (62A), and physcion 1-O-beta-D-glucoside (50A) purified
      from P. hypoleucum Ohwi for their effects on human mesangial cell proliferation
      and cytokines production in vitro. On a percentage basis, emodin had the highest
      suppressing activity on the human mesangial cells proliferation activated by IL
      1beta and IL-6. The IC50 of emodin on human mesangial cells proliferation were
      17.9+/-1.2 microM. In contrast to 49A, 50A, and 62A, emodin also decreased IL
      1beta, IL-6 and tumor necrosis factor-alpha (TNF-alpha) production in human
      mesangial cells activated with IL-1beta and IL-6. The IC50 of emodin on IL-1beta,
      IL-6 and TNF-alpha production in activated human mesangial cells were 16.6+/-1.8
      microM, 8.2+/-1.3 microM, and 9.5+/-1.6 microM, respectively. Moreover, IL-1beta
      and TNF-alpha mRNA expression in activated human mesangial cells was impaired by
      emodin. The intracellular free Ca2+ concentration ([Ca2+]i) in IL-1beta and IL-6
      activated human mesangial cells was decreased by emodin. It is unlikely that
      cytotoxicity was involved because no cell deaths were observable. We hypothesize
      that the inhibitory mechanisms of emodin on activated human mesangial cells
      proliferation may be related to the impairments of gene expression and production
      of cytokines and [Ca2+]i in the cells.

PMID- 11233993
TI  - Inotropic and chronotropic actions of Ilex latifolia inhibition of adenosine-5 '
      triphosphatases as a possible mechanism.
AB  - Ilex latifolia is widely used as an ingredient to prepare traditional beverage
      drinks in southern China. In fact, various Ilex species have been used in Chinese
      folk medicine to treat coronary heart diseases. The mode of action is believed to
      be mediated by their coronary vasodilative effects. In this study, the water
      extract of the leaves of Ilex latifolia (IK-TP) was shown to increase the
      contractility and decrease the frequency of contraction in an isolated rat heart
      perfusion system. IK-TP was found to inhibit Na+/K+-ATPase activities in rat
      heart sarcolemma, rat brain microsomes and a purified enzyme from porcine
      cerebral cortex. IK-TP also inhibited Ca2+-dependent ATPase at a similar dose.
      Following exposure of the isolated rat heart to IK-TP at a dose that produces
      pronounced cardiac effects, inhibition of Na+/K+-ATPase activity can be readily
      detected in the heart. This study suggests the presence of ATPase inhibitory
      compounds in Ilex latifolia with specificities different from that of ouabain.

PMID- 11233995
TI  - Inhibition by retinoids of antigen-induced IL-4 production in rat mast cell line
      RBL-2H3.
AB  - The retinoic acid receptor (RAR) agonists, Re80 and Am80, partially inhibited the
      antigen-induced IL-4 production by rat mast cell line RBL-2H3 in a concentration
      dependent manner (0.1 to 1000 nM). Both Re80 and Am80 also reduced the antigen
      induced increase in IL-4 mRNA levels. The RAR antagonist LE540 at 4 microM
      reversed Re80 (100 nM)- and Am80 (100 nM)-induced inhibition of IL-4 production.
      The retinoid X receptor agonist HX600 (1 microM) by itself did not affect IL-4
      production, but enhanced the inhibitory effect of Re80 (10 nM) and of Am80 (10
      nM). Cyclosporin A suppressed the antigen-induced IL-4 production almost
      completely at 0.3 microM. These findings indicated that the antigen-induced IL-4
      production by RBL-2H3 cells is partially inhibited by retinoids via RAR-dependent
      mechanisms.

PMID- 11233996
TI  - Chronic ingestion of ethanol stimulates lipogenic response in rat hepatocytes.
AB  - We isolated hepatocytes from rats chronically fed with ethanol and pair-fed
      control rats and incubated them both in the presence and absence of 100 mM
      ethanol in order to analyze the uptake into their lipids of several radiolabeled
      exogenous substrates. The hepatocytes treated chronically with ethanol showed
      higher lipogenic activity both in neutral lipids and phospholipids from serine,
      ethanolamine, glycerol and oleate. The only exception found was in the
      incorporation of choline into phosphatidylcholine (PC), which was lower in the
      hepatocytes from ethanol-fed rats than in the controls and was concomitant with a
      decrease in the PC levels of the ethanol-fed hepatocytes. The results obtained
      after exposing the cells to 100 mM ethanol in vitro indicate that in general the
      hepatocytes from ethanol-fed rats exhibit a higher lipogenic activity than the
      control cells. The only difference in the response to ethanol in vitro was found
      in the biosynthesis of phosphatidylserine (PS) from serine, which rose
      significantly in control cells but was unaffected in alcoholic hepatocytes. We
      put this difference in response down to specific adaptation to ethanol feeding.

PMID- 11233997
TI  - Pharmacological effects of naltriben as a ligand for opioid mu and kappa
      receptors in rat cerebral cortex.
AB  - Naltriben (NTB) has been used to differentiate the subtypes of delta opioid
      receptors, delta1 and delta2. However, there is considerable evidence suggesting
      that NTB may act on other types of opioid receptors too. We examined the effects
      of NTB on the specific binding of radiolabeled ligands for opioid mu and kappa2
      receptors, and the effects on the release of [3H]norepinephrine ([3H]NE) in rat
      cerebral cortex slices. NTB displaced the specific binding of [3H]DAMGO with Ki
      value of 19.79 +/- 1.12 nM in rat cortex membranes. Specific binding of
      [3H]diprenorphine ([3H]DIP) was inhibited by NTB with Ki value of 82.75 +/- 6.32
      nM in the presence of DAMGO and DPDPE. High K+ (15 mM)-stimulated release of
      [3H]NE was attenuated by DAMGO in rat cerebral cortex slices. NTB (30 nM) shifted
      the dose-response curve of DAMGO to the right and attenuated the maximal effect.
      In the meantime, NTB inhibited high K+-stimulated [3H]NE release at
      concentrations above 100 nM. The inhibitory effect of NTB was not attenuated by
      CTAP (10 nM) and naloxone (3 nM) but by higher concentration of naloxone (30 nM),
      nor-BNI (300 nM) and bremazocine (3 nM). These results indicate that NTB,
      depending on the dosage, could acts not only as an antagonist at delta but also
      as a noncompetitive antagonist for mu receptors, and as an agonist for kappa2
      receptors in rat cerebral cortex.

PMID- 11233998
TI  - Resveratrol decreases hyperalgesia induced by carrageenan in the rat hind paw.
AB  - The effect of resveratrol, an aryl hydrocarbon receptor (AhR) antagonist, known
      to inhibit inducible cyclooxygenase-2 (COX2) and its transcription were examined
      in a model of hyperalgesia induced by carrageenan in the rat. Pretreatment with
      resveratrol did not reverse swelling and edema, but reversed the hyperalgesia
      induced by local tissue injury provoked by carrageenan. This reversal, occurring
      at resveratrol concentrations as low as 2 mg/kg, lasted for at least 48 hours.
      The link with COX2 activity inhibition and COX2 gene transcription, as well as a
      potential AhR inhibitory effect, remain to be established.

PMID- 11233999
TI  - Multidrug resistance protein (MRP) activity in normal mature leukocytes and CD34
      positive hematopoietic cells from peripheral blood.
AB  - Multidrug resistance proteins (MRPs) such as MRP1, MRP2 and MRP3 are membrane
      efflux pumps involved in multidrug resistance and handling organic anions. In the
      present study, MRP activity was investigated in normal mature leucocytes and CD34
      positive hematopoietic cells from peripheral blood using the flow cytometric
      carboxy-2',7'-dichlorofluorescein (CF) efflux assay. Basal and similar cellular
      exports of CF, an anionic fluorescent dye substrate for MRP1 and MRP2
      transporters, were evidenced in lymphocytes whatever their subsets (CD3, CD4,
      CD8, CD20 and CD56 cells), in CD14 monocytes and in CD15 granulocytes whereas
      higher CF efflux was found in CD34 cells. Such outwardly-directed transports of
      CF were inhibited by known blockers of MRP function such as probenecid whereas
      the P-glycoprotein modulator verapamil did not alter the retention of the dye in
      the blood leukocytes. Peripheral mature blood leukocytes were moreover found to
      express MRP1 mRNAs and MRP1 protein as assessed by Northern-blot and Western-blot
      analyses, whereas MRP2 and MRP3 transcripts were not present or only at very low
      levels. Mature leukocytes therefore display basal constitutive MRP-related
      transport activity regardless of cell lineage and likely related to MRP1
      expression whereas higher MRP-related efflux can be detected in peripheral CD34
      hematopoietic cells.

PMID- 11234000
TI  - Protein encoding by both DNA strands.

PMID- 11234001
TI  - The impact of specialized enemies on the dimensionality of host dynamics.
AB  - Although individual species persist within a web of interactions with other
      species, data are usually gathered only from the focal species itself. We ask
      whether evidence of a species' interactions be detected and understood from
      patterns in the dynamics of that species alone. Theory predicts that strong
      coupling between a prey and a specialist predator/parasite should lead to an
      increase in the dimensionality of the prey's dynamics, whereas weak coupling
      should not. Here we describe a rare test of this prediction. Two natural enemies
      were added separately to replicate populations of a moth. For biological reasons
      that we identify here, the prediction of increased dimensionality was confirmed
      when a parasitoid wasp was added (although this increase had subtleties not
      previously appreciated), but the prediction failed for an added virus. Thus, an
      imprint of the interactions may be discerned within time-series data from
      component species of a system.

PMID- 11234003
TI  - A dusty torus around the luminous young star LkH alpha101.
AB  - A star forms when a cloud of dust and gas collapses. It is generally believed
      that this collapse first produces a flattened rotating disk, through which matter
      is fed onto the embryonic star at the centre of the disk. When the temperature
      and density at the centre of the star pass a critical threshold, thermonuclear
      fusion begins. The remaining disk, which can still contain up to 0.3 times the
      mass of the star, is then sculpted and eventually dissipated by the radiation and
      wind from the newborn star. But this picture of the structure and evolution of
      the disk remains speculative because of the lack of morphological data of
      sufficient resolution and uncertainties regarding the underlying physical
      processes. Here we present images of a young star, LkH alpha101, in which the
      structure of the inner accretion disk is resolved. We find that the disk is
      almost face-on, with a central gap (or cavity) and a hot inner edge. The cavity
      is bigger than previous theoretical predictions, and we infer that the position
      of the inner edge is probably determined by sublimation of dust grains by direct
      stellar radiation, rather than by disk-reprocessing or viscous-heating processes
      as usually assumed.

PMID- 11234002
TI  - Massive gene decay in the leprosy bacillus.
AB  - Leprosy, a chronic human neurological disease, results from infection with the
      obligate intracellular pathogen Mycobacterium leprae, a close relative of the
      tubercle bacillus. Mycobacterium leprae has the longest doubling time of all
      known bacteria and has thwarted every effort at culture in the laboratory.
      Comparing the 3.27-megabase (Mb) genome sequence of an armadillo-derived Indian
      isolate of the leprosy bacillus with that of Mycobacterium tuberculosis (4.41 Mb)
      provides clear explanations for these properties and reveals an extreme case of
      reductive evolution. Less than half of the genome contains functional genes but
      pseudogenes, with intact counterparts in M. tuberculosis, abound. Genome
      downsizing and the current mosaic arrangement appear to have resulted from
      extensive recombination events between dispersed repetitive sequences. Gene
      deletion and decay have eliminated many important metabolic activities including
      siderophore production, part of the oxidative and most of the microaerophilic and
      anaerobic respiratory chains, and numerous catabolic systems and their regulatory
      circuits.

PMID- 11234004
TI  - Experimental entanglement distillation and 'hidden' non-locality.
AB  - Entangled states are central to quantum information processing, including quantum
      teleportation, efficient quantum computation and quantum cryptography. In
      general, these applications work best with pure, maximally entangled quantum
      states. However, owing to dissipation and decoherence, practically available
      states are likely to be non-maximally entangled, partially mixed (that is, not
      pure), or both. To counter this problem, various schemes of entanglement
      distillation, state purification and concentration have been proposed. Here we
      demonstrate experimentally the distillation of maximally entangled states from
      non-maximally entangled inputs. Using partial polarizers, we perform a filtering
      process to maximize the entanglement of pure polarization-entangled photon pairs
      generated by spontaneous parametric down-conversion. We have also applied our
      methods to initial states that are partially mixed. After filtering, the
      distilled states demonstrate certain non-local correlations, as evidenced by
      their violation of a form of Bell's inequality. Because the initial states do not
      have this property, they can be said to possess 'hidden' non-locality.

PMID- 11234005
TI  - Fluid particle accelerations in fully developed turbulence.
AB  - The motion of fluid particles as they are pushed along erratic trajectories by
      fluctuating pressure gradients is fundamental to transport and mixing in
      turbulence. It is essential in cloud formation and atmospheric transport,
      processes in stirred chemical reactors and combustion systems, and in the
      industrial production of nanoparticles. The concept of particle trajectories has
      been used successfully to describe mixing and transport in turbulence, but issues
      of fundamental importance remain unresolved. One such issue is the Heisenberg
      Yaglom prediction of fluid particle accelerations, based on the 1941 scaling
      theory of Kolmogorov. Here we report acceleration measurements using a detector
      adapted from high-energy physics to track particles in a laboratory water flow at
      Reynolds numbers up to 63,000. We find that, within experimental errors,
      Kolmogorov scaling of the acceleration variance is attained at high Reynolds
      numbers. Our data indicate that the acceleration is an extremely intermittent
      variable--particles are observed with accelerations of up to 1,500 times the
      acceleration of gravity (equivalent to 40 times the root mean square
      acceleration). We find that the acceleration data reflect the anisotropy of the
      large-scale flow at all Reynolds numbers studied.

PMID- 11234006
TI  - Prediction of absolute crystal-nucleation rate in hard-sphere colloids.
AB  - Crystal nucleation is a much-studied phenomenon, yet the rate at which it occurs
      remains difficult to predict. Small crystal nuclei form spontaneously in
      supersaturated solutions, but unless their size exceeds a critical value--the so
      called critical nucleus--they will re-dissolve rather than grow. It is this rate
      limiting step that has proved difficult to probe experimentally. The crystal
      nucleation rate depends on Pcrit, the (very small) probability that a critical
      nucleus forms spontaneously, and on a kinetic factor (kappa) that measures the
      rate at which critical nuclei subsequently grow. Given the absence of a priori
      knowledge of either quantity, classical nucleation theory is commonly used to
      analyse crystal nucleation experiments, with the unconstrained parameters
      adjusted to fit the observations. This approach yields no 'first principles'
      prediction of absolute nucleation rates. Here we approach the problem from a
      different angle, simulating the nucleation process in a suspension of hard
      colloidal spheres, to obtain quantitative numerical predictions of the crystal
      nucleation rate. We find large discrepancies between the computed nucleation
      rates and those deduced from experiments: the best experimental estimates of
      Pcrit seem to be too large by several orders of magnitude.

PMID- 11234007
TI  - Formation of thermally stable alkylidene layers on a catalytically active
      surface.
AB  - Materials containing organic-inorganic interfaces usually display a combination
      of molecular and solid-state properties, which are of interest for applications
      ranging from chemical sensing to microelectronics and catalysis. Thiols--organic
      compounds carrying a SH group--are widely used to anchor organic layers to gold
      surfaces, because gold is catalytically sufficiently active to replace relatively
      weak S-H bonds with Au-S bonds, yet too inert to attack C-C and C-H bonds in the
      organic layer. But although several methods of functionalizing the surfaces of
      semiconductors, oxides and metals are known, it remains difficult to attach a
      wide range of more complex organic species. Organic layers could, in principle,
      be formed on the surfaces of metals that are capable of inserting into strong
      bonds, but such surfaces catalyse the decomposition of organic layers at
      temperatures above 400 to 600 K, through progressive C-H and C-C bond breaking.
      Here we report that cycloketones adsorbed on molybdenum carbide, a material known
      to catalyse a variety of hydrocarbon conversion reactions, transform into surface
      bound alkylidenes stable to above 900 K. We expect that this chemistry can be
      used to create a wide range of exceptionally stable organic layers on molybdenum
      carbide.

PMID- 11234008
TI  - Recent mass balance of polar ice sheets inferred from patterns of global sea
      level change.
AB  - Global sea level is an indicator of climate change, as it is sensitive to both
      thermal expansion of the oceans and a reduction of land-based glaciers. Global
      sea-level rise has been estimated by correcting observations from tide gauges for
      glacial isostatic adjustment--the continuing sea-level response due to melting of
      Late Pleistocene ice--and by computing the global mean of these residual trends.
      In such analyses, spatial patterns of sea-level rise are assumed to be signals
      that will average out over geographically distributed tide-gauge data. But a long
      history of modelling studies has demonstrated that non-uniform--that is, non
      eustatic--sea-level redistributions can be produced by variations in the volume
      of the polar ice sheets. Here we present numerical predictions of gravitationally
      consistent patterns of sea-level change following variations in either the
      Antarctic or Greenland ice sheets or the melting of a suite of small mountain
      glaciers. These predictions are characterized by geometrically distinct patterns
      that reconcile spatial variations in previously published sea-level records.
      Under the--albeit coarse--assumption of a globally uniform thermal expansion of
      the oceans, our approach suggests melting of the Greenland ice complex over the
      last century equivalent to -0.6 mm yr(-1) of sea-level rise.

PMID- 11234009
TI  - Geological constraints on tidal dissipation and dynamical ellipticity of the
      Earth over the past three million years.
AB  - The evolution of the Solar System has been shown to be chaotic, which limits our
      ability to retrace the orbital and precessional motion of the Earth over more
      than 35-50 Myr (ref. 2). Moreover, the precession, obliquity and insolation
      parameters can also be influenced by secular variations in the tidal dissipation
      and dynamical ellipticity of the Earth induced by glacial cyclicity and mantle
      convection. Here we determine the average values of these dissipative effects
      over the past three million years. We have computed the optimal fit between an
      exceptional palaeoclimate record from the eastern Mediterranean Sea and a model
      of the astronomical and insolation history by testing a number of values for the
      tidal dissipation and dynamical ellipticity parameters. We find that the combined
      effects of dynamical ellipticity and tidal dissipation were, on average,
      significantly lower over the past three million years, compared to their present
      day values (determined from artificial satellite data and lunar ranging). This
      secular variation associated with the Plio-Pleistocene ice load history has
      caused an average acceleration in the Earth's rotation over the past 3 Myr, which
      needs to be considered in the construction of astronomical timescales and in
      research into the stationarity of phase relations in the ocean-climate system
      through time.

PMID- 11234010
TI  - Cranial design and function in a large theropod dinosaur.
AB  - Finite element analysis (FEA) is used by industrial designers and biomechanicists
      to estimate the performance of engineered structures or human skeletal and soft
      tissues subjected to varying regimes of stress and strain. FEA is rarely applied
      to problems of biomechanical design in animals, despite its potential to inform
      structure-function analysis. Non-invasive techniques such as computed tomography
      scans can be used to generate accurate three-dimensional images of structures,
      such as skulls, which can form the basis of an accurate finite element model.
      Here we have applied this technique to the long skull of the large carnivorous
      theropod dinosaur Allosaurus fragilis. We have generated the most geometrically
      complete and complex FEA model of the skull of any extinct or extant organism and
      used this to test its mechanical properties and examine, in a quantitative way,
      long-held hypotheses concerning overall shape and function. The combination of a
      weak muscle-driven bite force, a very 'light' and 'open' skull architecture and
      unusually high cranial strength, suggests a very specific feeding behaviour for
      this animal. These results demonstrate simply the inherent potential of FEA for
      testing mechanical behaviour in fossils in ways that, until now, have been
      impossible.

PMID- 11234011
TI  - Genetic evidence against panmixia in the European eel.
AB  - The panmixia hypothesis--that all European eel (Anguilla anguilla) migrate to the
      Sargasso Sea for reproduction and comprise a single, randomly mating population-
      is widely accepted. If true, then this peculiar life history strategy would
      directly impact the population genetics of this species, and eels from European
      and north African rivers should belong to the same breeding population through
      the random dispersal of larvae. To date, the panmixia hypothesis has remained
      unchallenged: genetic studies realized on eel's mitochondrial DNA failed to
      detect any genetic structure; and a similar lack of structure was found using
      allozymes, with the exception of clinal variation imposed by selection. Here we
      have used highly polymorphic genetic markers that provide better resolution to
      investigate genetic structure in European eel. Analysis of seven microsatellite
      loci among 13 samples from the north Atlantic, the Baltic Sea and the
      Mediterranean Sea basins reveals that there is global genetic differentiation.
      Moreover, pairwise Cavalli-Sforza and Edwards chord distances correlate
      significantly with coastal geographical distance. This pattern of genetic
      structure implies non-random mating and restricted gene flow among eels from
      different sampled locations, which therefore refute the hypothesis of panmixia.
      Consequently, the reproductive biology of European eel must be reconsidered.

PMID- 11234012
TI  - Temporal dynamics of a neural solution to the aperture problem in visual area MT
      of macaque brain.
AB  - A critical step in the interpretation of the visual world is the integration of
      the various local motion signals generated by moving objects. This process is
      complicated by the fact that local velocity measurements can differ depending on
      contour orientation and spatial position. Specifically, any local motion detector
      can measure only the component of motion perpendicular to a contour that extends
      beyond its field of view. This "aperture problem" is particularly relevant to
      direction-selective neurons early in the visual pathways, where small receptive
      fields permit only a limited view of a moving object. Here we show that neurons
      in the middle temporal visual area (known as MT or V5) of the macaque brain
      reveal a dynamic solution to the aperture problem. MT neurons initially respond
      primarily to the component of motion perpendicular to a contour's orientation,
      but over a period of approximately 60 ms the responses gradually shift to encode
      the true stimulus direction, regardless of orientation. We also report a
      behavioural correlate of these neural responses: the initial velocity of pursuit
      eye movements deviates in a direction perpendicular to local contour orientation,
      suggesting that the earliest neural responses influence the oculomotor response.

PMID- 11234013
TI  - A sodium-channel mutation causes isolated cardiac conduction disease.
AB  - Cardiac conduction disorders slow the heart rhythm and cause disability in
      millions of people worldwide. Inherited mutations in SCN5A, the gene encoding the
      human cardiac sodium (Na+) channel, have been associated with rapid heart rhythms
      that occur suddenly and are life-threatening; however, a chief function of the
      Na+ channel is to initiate cardiac impulse conduction. Here we provide the first
      functional characterization of an SCN5A mutation that causes a sustained,
      isolated conduction defect with pathological slowing of the cardiac rhythm. By
      analysing the SCN5A coding region, we have identified a single mutation in five
      affected family members; this mutation results in the substitution of cysteine
      514 for glycine (G514C) in the channel protein. Biophysical characterization of
      the mutant channel shows that there are abnormalities in voltage-dependent
      'gating' behaviour that can be partially corrected by dexamethasone, consistent
      with the salutary effects of glucocorticoids on the clinical phenotype.
      Computational analysis predicts that the gating defects of G514C selectively slow
      myocardial conduction, but do not provoke the rapid cardiac arrhythmias
      associated previously with SCN5A mutations.

PMID- 11234014
TI  - The voltage-sensitive sodium channel is a bell-shaped molecule with several
      cavities.
AB  - Voltage-sensitive membrane channels, the sodium channel, the potassium channel
      and the calcium channel operate together to amplify, transmit and generate
      electric pulses in higher forms of life. Sodium and calcium channels are involved
      in cell excitation, neuronal transmission, muscle contraction and many functions
      that relate directly to human diseases. Sodium channels--glycosylated proteins
      with a relative molecular mass of about 300,000 (ref. 5)--are responsible for
      signal transduction and amplification, and are chief targets of anaesthetic drugs
      and neurotoxins. Here we present the three-dimensional structure of the voltage
      sensitive sodium channel from the eel Electrophorus electricus. The 19 A
      structure was determined by helium-cooled cryo-electron microscopy and single
      particle image analysis of the solubilized sodium channel. The channel has a bell
      shaped outer surface of 135 A in height and 100 A in side length at the square
      shaped bottom, and a spherical top with a diameter of 65 A. Several inner
      cavities are connected to four small holes and eight orifices close to the
      extracellular and cytoplasmic membrane surfaces. Homologous voltage-sensitive
      calcium and tetrameric potassium channels, which regulate secretory processes and
      the membrane potential, may possess a related structure.

PMID- 11234015
TI  - RGS2 regulates signal transduction in olfactory neurons by attenuating activation
      of adenylyl cyclase III.
AB  - The heterotrimeric G-protein Gs couples cell-surface receptors to the activation
      of adenylyl cyclases and cyclic AMP production (reviewed in refs 1, 2). RGS
      proteins, which act as GTPase-activating proteins (GAPs) for the G-protein alpha
      subunits alpha(i) and alpha(q), lack such activity for alpha(s) (refs 3-6). But
      several RGS proteins inhibit cAMP production by Gs-linked receptors. Here we
      report that RGS2 reduces cAMP production by odorant-stimulated olfactory
      epithelium membranes, in which the alpha(s) family member alpha(olf) links
      odorant receptors to adenylyl cyclase activation. Unexpectedly, RGS2 reduces
      odorant-elicited cAMP production, not by acting on alpha(olf) but by inhibiting
      the activity of adenylyl cyclase type III, the predominant adenylyl cyclase
      isoform in olfactory neurons. Furthermore, whole-cell voltage clamp recordings of
      odorant-stimulated olfactory neurons indicate that endogenous RGS2 negatively
      regulates odorant-evoked intracellular signalling. These results reveal a
      mechanism for controlling the activities of adenylyl cyclases, which probably
      contributes to the ability of olfactory neurons to discriminate odours.

PMID- 11234016
TI  - Recognition of haemagglutinins on virus-infected cells by NKp46 activates lysis
      by human NK cells.
AB  - Natural killer (NK) cells destroy virus-infected and tumour cells, apparently
      without the need for previous antigen stimulation. In part, target cells are
      recognized by their diminished expression of major histocompatibility complex
      (MHC) class I molecules, which normally interact with inhibitory receptors on the
      NK cell surface. NK cells also express triggering receptors that are specific for
      non-MHC ligands; but the nature of the ligands recognized on target cells is
      undefined. NKp46 is thought to be the main activating receptor for human NK
      cells. Here we show that a soluble NKp46-immunoglobulin fusion protein binds to
      both the haemagglutinin of influenza virus and the haemagglutinin-neuraminidase
      of parainfluenza virus. In a substantial subset of NK cells, recognition by NKp46
      is required to lyse cells expressing the corresponding viral glycoproteins. The
      binding requires the sialylation of NKp46 oligosaccharides, which is consistent
      with the known sialic binding capacity of the viral glycoproteins. These findings
      indicate how NKp46-expressing NK cells may recognize target cells infected by
      influenza or parainfluenza without the decreased expression of target-cell MHC
      class I protein.

PMID- 11234017
TI  - Identification of CRE1 as a cytokinin receptor from Arabidopsis.
AB  - Cytokinins are a class of plant hormones that are central to the regulation of
      cell division and differentiation in plants. It has been proposed that they are
      detected by a two-component system, because overexpression of the histidine
      kinase gene CKI1 induces typical cytokinin responses and genes for a set of
      response regulators of two-component systems can be induced by cytokinins. Two
      component systems use a histidine kinase as an environmental sensor and rely on a
      phosphorelay for signal transduction. They are common in microorganisms, and are
      also emerging as important signal detection routes in plants. Here we report the
      identification of a cytokinin receptor. We identified Arabidopsis cre1 (cytokinin
      response 1) mutants, which exhibited reduced responses to cytokinins. The mutated
      gene CRE1 encodes a histidine kinase. CRE1 expression conferred a cytokinin
      dependent growth phenotype on a yeast mutant that lacked the endogenous histidine
      kinase SLN1 (ref. 10), providing direct evidence that CRE1 is a cytokinin
      receptor. We also provide evidence that cytokinins can activate CRE1 to initiate
      phosphorelay signalling.

PMID- 11234018
TI  - cdc2 links the Drosophila cell cycle and asymmetric division machineries.
AB  - Asymmetric cell divisions can be mediated by the preferential segregation of cell
      fate determinants into one of two sibling daughters. In Drosophila neural
      progenitors, Inscuteable, Partner of Inscuteable and Bazooka localize as an
      apical cortical complex at interphase, which directs the apical-basal orientation
      of the mitotic spindle as well as the basal/cortical localization of the cell
      fate determinants Numb and/or Prospero during mitosis. Although localization of
      these proteins shows dependence on the cell cycle, the involvement of cell-cycle
      components in asymmetric divisions has not been demonstrated. Here we show that
      neural progenitor asymmetric divisions require the cell-cycle regulator cdc2. By
      attenuating Drosophila cdc2 function without blocking mitosis, normally
      asymmetric progenitor divisions become defective, failing to correctly localize
      asymmetric components during mitosis and/or to resolve distinct sibling fates.
      cdc2 is not necessary for initiating apical complex formation during interphase;
      however, maintaining the asymmetric localization of the apical components during
      mitosis requires Cdc2/B-type cyclin complexes. Our findings link cdc2 with
      asymmetric divisions, and explain why the asymmetric localization of molecules
      like Inscuteable show cell-cycle dependence.

PMID- 11234019
TI  - Opposing effects of Ets and Id proteins on p16INK4a expression during cellular
      senescence.
AB  - The p16INK4a cyclin-dependent kinase inhibitor is implicated in replicative
      senescence, the state of permanent growth arrest provoked by cumulative cell
      divisions or as a response to constitutive Ras-Raf-MEK signalling in somatic
      cells. Some contribution to senescence presumably underlies the importance of
      p16INK4a as a tumour suppressor but the mechanisms regulating its expression in
      these different contexts remain unknown. Here we demonstrate a role for the Ets1
      and Ets2 transcription factors based on their ability to activate the p16INK4a
      promoter through an ETS-binding site and their patterns of expression during the
      lifespan of human diploid fibroblasts. The induction of p16INK4a by Ets2, which
      is abundant in young human diploid fibroblasts, is potentiated by signalling
      through the Ras-Raf-MEK kinase cascade and inhibited by a direct interaction with
      the helix-loop-helix protein Id1 (ref. 11). In senescent cells, where the Ets2
      levels and MEK signalling decline, the marked increase in p16INK4a expression is
      consistent with the reciprocal reduction of Id1 and accumulation of Ets1.

PMID- 11234020
TI  - Structural determinants for regulation of phosphodiesterase by a G protein at 2.0
      A.
AB  - A multitude of heptahelical receptors use heterotrimeric G proteins to transduce
      signals to specific effector target molecules. The G protein transducin, Gt,
      couples photon-activated rhodopsin with the effector cyclic GMP
      phosophodiesterase (PDE) in the vertebrate phototransduction cascade. The
      interactions of the Gt alpha-subunit (alpha(t)) with the inhibitory PDE gamma
      subunit (PDEgamma) are central to effector activation, and also enhance visual
      recovery in cooperation with the GTPase-activating protein regulator of G-protein
      signalling (RGS)-9 (refs 1-3). Here we describe the crystal structure at 2.0 A of
      rod transducin alpha x GDP x AlF4- in complex with the effector molecule PDEgamma
      and the GTPase-activating protein RGS9. In addition, we present the independently
      solved crystal structures of the RGS9 RGS domain both alone and in complex with
      alpha(t/i1) x GDP x AlF4-. These structures reveal insights into effector
      activation, synergistic GTPase acceleration, RGS9 specificity and RGS activity.
      Effector binding to a nucleotide-dependent site on alpha(t) sequesters PDEgamma
      residues implicated in PDE inhibition, and potentiates recruitment of RGS9 for
      hydrolytic transition state stabilization and concomitant signal termination.

PMID- 11234021
TI  - Desperately seeking aliens.
AB  - Belief that intelligent life is commonplace in the Universe was taken for granted
      by scholars and scientists until well into the nineteenth century. Space travel
      since the late 1950s reignited the debate, which even now attracts discussion by
      serious, professional scientists. And although statisticians might lobby that
      life must surely exist somewhere in the Universe, the evolution of what we
      perceive as 'intelligent life' seems utterly improbable--elsewhere as well as on
      Earth. Can we free ourselves of our animist fantasies and accept that all alien
      forms of intelligent life are, and always have been, imaginary?

PMID- 11234022
TI  - The habitat and nature of early life.
AB  - Earth is over 4,500 million years old. Massive bombardment of the planet took
      place for the first 500-700 million years, and the largest impacts would have
      been capable of sterilizing the planet. Probably until 4,000 million years ago or
      later, occasional impacts might have heated the ocean over 100 degrees C. Life on
      Earth dates from before about 3,800 million years ago, and is likely to have gone
      through one or more hot-ocean 'bottlenecks'. Only hyperthermophiles (organisms
      optimally living in water at 80-110 degrees C) would have survived. It is
      possible that early life diversified near hydrothermal vents, but hypotheses that
      life first occupied other pre-bottleneck habitats are tenable (including transfer
      from Mars on ejecta from impacts there). Early hyperthermophile life, probably
      near hydrothermal systems, may have been non-photosynthetic, and many
      housekeeping proteins and biochemical processes may have an original hydrothermal
      heritage. The development of anoxygenic and then oxygenic photosynthesis would
      have allowed life to escape the hydrothermal setting. By about 3,500 million
      years ago, most of the principal biochemical pathways that sustain the modern
      biosphere had evolved, and were global in scope.

PMID- 11234023
TI  - Life in extreme environments.
AB  - Each recent report of liquid water existing elsewhere in the Solar System has
      reverberated through the international press and excited the imagination of
      humankind. Why? Because in the past few decades we have come to realize that
      where there is liquid water on Earth, virtually no matter what the physical
      conditions, there is life. What we previously thought of as insurmountable
      physical and chemical barriers to life, we now see as yet another niche
      harbouring 'extremophiles'. This realization, coupled with new data on the
      survival of microbes in the space environment and modelling of the potential for
      transfer of life between celestial bodies, suggests that life could be more
      common than previously thought. Here we examine critically what it means to be an
      extremophile, and the implications of this for evolution, biotechnology and
      especially the search for life in the Universe.

PMID- 11234024
TI  - Chance and necessity: the evolution of morphological complexity and diversity.
AB  - The primary foundation for contemplating the possible forms of life elsewhere in
      the Universe is the evolutionary trends that have marked life on Earth. For its
      first three billion years, life on Earth was a world of microscopic forms, rarely
      achieving a size greater than a millimetre or a complexity beyond two or three
      cell types. But in the past 600 million years, the evolution of much larger and
      more complex organisms has transformed the biosphere. Despite their disparate
      forms and physiologies, the evolution and diversification of plants, animals,
      fungi and other macroforms has followed similar global trends. One of the most
      important features underlying evolutionary increases in animal and plant size,
      complexity and diversity has been their modular construction from reiterated
      parts. Although simple filamentous and spherical forms may evolve wherever
      cellular life exists, the evolution of motile, modular mega-organisms might not
      be a universal pattern.

PMID- 11234025
TI  - The search for extraterrestrial intelligence.
AB  - As far as we know, humanity is alone in the Universe: there is no definite
      evidence for the existence of extraterrestrial life, let alone extraterrestrial
      civilizations (ETCs) capable of communicating or travelling over interstellar
      distances. Yet popular speculation about the existence of ETCs abounds, including
      reports of alien visitations either now or in the past. But there is a middle
      way. It is now possible to put limits on the existence of ETCs of varying
      capabilities, within arbitrary distances from the Solar System, and conceive of
      real-world strategies whereby we might communicate with ETCs, or they with us.

PMID- 11234026
TI  - Humans in space.
AB  - Many successful space missions over the past 40 years have highlighted the
      advantages and necessity of humans in the exploration of space. But as space
      travel becomes ever more feasible in the twenty-first century, the health and
      safety of future space explorers will be paramount. In particular, understanding
      the risks posed by exposure to radiation and extended weightlessness will be
      crucial if humans are to travel far from Earth.

PMID- 11234027
TI  - Where are the dolphins?
AB  - Interest in extraterrestrial life has tended to focus on a search for extrasolar
      planets similar to the Earth. But what of forms of intelligent life that are very
      different from those found on Earth? Some features of life will not be peculiar
      to our planet, and alien life will resemble ours in such universals. But if
      intelligent, non-humanoid aliens exist, where might they be? Would they wish to
      visit Earth and would we know if they did?

PMID- 11234028
TI  - Biomedical boom, forget the rest?

PMID- 11234029
TI  - Europe's infrastructure failure.

PMID- 11234030
TI  - Wheels start to turn for mutant mouse archive.

PMID- 11234031
TI  - European Union moves to curb moratorium on transgenic plants.

PMID- 11234033
TI  - India promises more earthquake research.

PMID- 11234032
TI  - Canada's BSE fears 'groundless'.

PMID- 11234034
TI  - First Bush budget set to favour life sciences.

PMID- 11234035
TI  - Farming accused of eco-damage.

PMID- 11234036
TI  - Residents wait for return to Japanese volcano island.

PMID- 11234037
TI  - Small payout over Green Bank telescope cheers astronomers.

PMID- 11234038
TI  - Biologists urge US to build marine reserves.

PMID- 11234040
TI  - Climate change offers bleak future.

PMID- 11234039
TI  - Scientists seek solidarity in oaths.

PMID- 11234041
TI  - Silicon in optoelectronics. Let there be light.

PMID- 11234042
TI  - Oxide formation: reaction details studied, reported in brief.

PMID- 11234043
TI  - Varied ecosystems need different fire protection.

PMID- 11234044
TI  - Opposition to animal law is not lack of concern.

PMID- 11234045
TI  - Lombroso and Tolstoy.

PMID- 11234046
TI  - The artistry of nature.

PMID- 11234047
TI  - The bite of Allosaurus.

PMID- 11234049
TI  - Sediments to planetary motion.

PMID- 11234048
TI  - A 3D view of sodium channels.

PMID- 11234050
TI  - Ecology. Bagging the lag.

PMID- 11234051
TI  - Turbulence. Go with the flow.

PMID- 11234052
TI  - Muscle strength in overwintering bears.

PMID- 11234053
TI  - Particulate emission from biomass combustion.

PMID- 11234054
TI  - An early Cretaceous pellet.

PMID- 11234055
TI  - Nuclear offense versus defense.

PMID- 11234057
TI  - Japan. Fusion scientists urge closer look at ITER.

PMID- 11234056
TI  - Paleoanthropology.  Scientists spar over claims of earliest human ancestor.

PMID- 11234058
TI  - 2002 spending.  First Bush budget may put science on diet.

PMID- 11234059
TI  - European science. Max Planck takes an e-publishing plunge.

PMID- 11234060
TI  - Neurobiology.   A discriminating taste for bitter.

PMID- 11234061
TI  - Women in science.   Court to hear charges by Harvard researcher.

PMID- 11234062
TI  - Astrophysics.   Cluster reveals Earth's rippling magnetic field.

PMID- 11234063
TI  - Planetary science.   Strange doings on a NEAR-struck asteroid.

PMID- 11234064
TI  - Paleontology.  Whiff of gas points to impact mass extinction.

PMID- 11234065
TI  - Astrophysics.  New headaches for U.S.-Russia experiment.

PMID- 11234067
TI  - High-energy physics. B-meson factories make a "number from hell".

PMID- 11234066
TI  - Endangered species.  West's energy woes threaten salmon runs.

PMID- 11234068
TI  - Papal science. Science and religion advance together at Pontifical Academy.

PMID- 11234069
TI  - Papal science.  Vatican Observatory takes long view of exploring the heavens.

PMID- 11234070
TI  - Computer models.  Paleontologists learn to shake up virtual bones.

PMID- 11234071
TI  - Superconductivity.   Material sets record for metal compounds.

PMID- 11234072
TI  - Chinese Academy of Sciences. In China, publish or perish is  becoming the new
      reality.

PMID- 11234073
TI  - What is a planet?

PMID- 11234075
TI  - Politics of the census.

PMID- 11234074
TI  - ADHD: disorder or discipline problem?

PMID- 11234076
TI  - Demography.   Prospects for human longevity.

PMID- 11234077
TI  - Paleoclimate.   A slow dance for El Nino.

PMID- 11234078
TI  - Paleoclimate.   Was the Medieval Warm Period global?

PMID- 11234079
TI  - Cell cycle.  Centrioles at the checkpoint.

PMID- 11234080
TI  - Electronics.   Toward paperlike displays.

PMID- 11234081
TI  - Immunology.   B cell receptor rehabilitation--pausing to reflect.

PMID- 11234082
TI  - Evolution.  A horn for an eye.

PMID- 11234083
TI  - Neuroscience.   Drums keep pounding a rhythm in the brain.

PMID- 11234084
TI  - Price survey. Pacemaker prices dropping.

PMID- 11234085
TI  - Selling safety: needle law change won't be painless.

PMID- 11234086
TI  - [Acute appendicitis and its complications. Diagnosis, treatment].

PMID- 11234087
TI  - [Influenza. Epidemiology, diagnosis, treatment, prevention].

PMID- 11234088
TI  - [Clinical examination and complimentary investigations of the anus].
AB  - Precise history-taking and a complete clinical examination including all the
      components of the perineum guide diagnosis in anorectal disorders and most often
      indicate treatment. Ancillary investigations are sometimes needed for more
      precise diagnosis or to complete pretreatment workup. Such additional
      investigations should always be discussed, indicated and interpreted in view of
      the clinical examination.

PMID- 11234089
TI  - [Hemorrhoids and hemorrhoidal disorders].
AB  - Haemorrhoids are normal anatomic components of the anal canal, involved in the
      fine adjustment of continence. This physiological role requires normal size and
      location. The anatomical aspects of haemorrhoids do not reflect their symptomatic
      expression. Natural evolution of haemorrhoids is benign, but most often chronic,
      with spontaneous worsening. Despite recent advances in medical and instrumental
      treatments, about 10% of the patients need a radical and definitive treatment
      relying on surgery. This comfort-oriented surgery should only be proposed to
      handicapped patients, after information about the rare (but possible)
      complications and the unavoidable transitory postoperative discomfort.

PMID- 11234090
TI  - [Anal suppurations].
AB  - Anal suppurations can be classified according to their origin: from the anal
      canal, from above the anal canal, or independent from the ano-rectum. Wherever
      suppuration comes from, an abscess can be present at the acute phase. Anal
      fistulas represent about 70% of anal suppurations. They always begin by
      cryptoglandular infection, which can spread to the intersphincteric space and
      then pass through the anal sphincter. Treatment of anal fistula is a double
      challenge: healing the suppuration, and preserving anal continence. Among
      suppurations independent from the ano-rectum pilonidal disease is the most
      frequent (15% of the suppurations). Other causes of ano-perineal suppurations are
      infected fissure, Verneuil's disease, and gland, recto-vaginal fistulas and
      Crohn's disease.

PMID- 11234092
TI  - [Epidermoid cancer of the anus].
AB  - Anal cancer is a rare neoplasm: 1 anal cancer for 100 colorectal cancers. The
      development of anal cancer is associated with infection by human papillomavirus,
      which is usually sexually transmitted. Determination of tumour stage is important
      for planning optimal therapy and for predicting prognosis accurately. Initial
      work-up is primarily clinical with additional information from abdominal and
      transanorectal ultrasonography, and chest radiography. A classification mixing
      TNM (Tumour, Nodes, Metastasis) and ultrasonographic examination of the extension
      in depth allows to make a therapeutic decision and to follow it up. Conservative
      treatment is almost always possible. Concomitant external beam radiation therapy
      and chemotherapy are the standard to combination treatment. Surgical treatment
      remains indicated in rare cases.

PMID- 11234091
TI  - [Anal fissures and fissurations].
AB  - The anal fissure syndrome is characterized by a triad: anal pain accompanying
      defaecation; one or several anal ulcers; anal internal sphincter hypertonia.
      Fissure in ano is the most frequent cause; diagnosis is clinical; pathogenic
      understanding and treatment are in rapid progress. Secondary anal fissurations
      are characterized by a less typical syndrome, by the necessity of special
      investigations for diagnosis and by an etiology-oriented treatment. Their causes
      are multiple. The most frequent are infectious, essentially sexually transmitted
      diseases, and the tumour, mainly anal epidermoid cancer.

PMID- 11234093
TI  - [Anal incontinence].
AB  - Contrary to a widespread opinion, anal incontinence is a frequent condition in
      men and women, and not only a disease of advanced age. This condition is so
      devastating socially and personally that the afflicted individual is often too
      embarrassed to bring it to the attention of his physician. An accurate history, a
      physical examination and additional anorectal physiology testing (anorectal
      manometry and anal endosonography) document the aetiology. The first line of
      treatment is medical including bowel management and neuromuscular reeducation. In
      case of failure, according to the cause, and with due regard to the impact on the
      quality of life, surgery can be performed. It is essential to know the preventive
      measures which are the only means for decreasing the incidence of anal
      incontinence.

PMID- 11234094
TI  - [Chronic perineal pain].
AB  - Chronic perineal pain, too easily considered in the past as psychogenic, has
      undergone significant reshapings in recent years because of a better
      understanding of pathophysiology. Progress in functional investigations,
      especially electrophysiological tests, has allowed to define new clinical
      entities such as pudendal neuralgia or pain linked to pelvic floor disorders.
      Treatments have been improved, but remain empirical outside these well defined
      entities. In practice, clinical examination is the main diagnostic step, which
      allows to exclude common anorectal or pelviperineal lesions, and to consider
      additional investigations. However diagnosis may remain entirely clinical in some
      typical presentations.

PMID- 11234095
TI  - [Treatment of ectopic pregnancy with methotrexate].

PMID- 11234096
TI  - [Sexually transmitted diseases of the anus].
AB  - Sexually transmitted diseases, despite vigorous efforts in prevention, are still
      existing and may provide portal of entry for human immunodeficiency virus
      transmission. Syphilis and gonococcal infection are decreasing but remain a
      problem in developing countries and their return cannot be excluded, despite
      active therapy. In industrial countries, viral infections are expanding. Herpes
      genitalis is the most common cause of genito-anal ulceration and anogenital warts
      have been steadily rising in the past decades. Some human papillomavirus
      genotypes are oncogenic. No treatment is able to eradicate them.

PMID- 11234097
TI  - [Medical demography: time of failure].

PMID- 11234098
TI  - [Atropine. Principles and rules of utilization].

PMID- 11234099
TI  - [Monofactorial heredity. Construction and interpretation of genealogic trees.
      Principles of genetic counseling].

PMID- 11234100
TI  - [Parotid tumors. Diagnostic approach].

PMID- 11234101
TI  - [Atherosclerosis. Pathologic anatomy, physiopathology, epidemiology and risk
      factors, prevention].

PMID- 11234102
TI  - [Antibiotic use in animal breeding].

PMID- 11234103
TI  - [Conversion hysteria. Diagnosis, treatment].

PMID- 11234104
TI  - A psychoanalytic reading of Peter Hoeg's novel Miss Smilla's Feeling for Snow.
AB  - The author presents a psychoanalytic reading of the Danish author Peter Hoeg's
      masterpiece 'Miss Smilla's Feeling for Snow', focusing on the special linguistic
      style of the novel. Further, the author puts forward an interpretation of the
      heroine, seeing her as a literary example of female bisexuality. Investigating
      the heroine's fate, the author discusses Miss Smilla's phallic defence and
      identity. The narrative technique in Hoeg's novel is analysed through Lacan's
      concepts of the Real, the Imaginary and the Symbolic. The main figure is
      interpreted as an imaginary example of female bisexuality. Miss Smilla has
      neither an unambiguous gender identity nor ethnicity. The heroine is pictured in
      a conflict between two cultures: the Greenlandish and the western European, and
      her bisexuality both reflects this and is part of it. The author proposes to
      interpret a significant memory from Smilla's early childhood as an example of a
      castration phantasy, which retroactively gives new significance to the little
      girl's pre-oedipal frustration.

PMID- 11234105
TI  - Postmodern psychoanalysis.
AB  - In keeping with the spirit of the postmodern, the author suggests that
      psychoanalysts should be wary of subscribing to a set of rules and/or a proper
      method for the conduct of psychoanalysis. He puts forward instead the suggestion
      that some patients do well with certain rules and not with others, and offers a
      brief report concerning a group of patients who were unable to 'live by the
      rules' to support such a viewpoint. He suggests that a corollary of this
      perspective is one that links the analyst's own capacity to live within or
      outside of rules to his or her effectiveness with these particular patients. From
      this unique illustrative group, the general conclusion is offered that only the
      singular goal of understanding in depth is the proper guiding rule of
      psychoanalysis.

PMID- 11234107
TI  - The link and the other.
AB  - The author begins by drawing attention to the current crisis in psychoanalysis,
      in which, following the great initial discoveries, he considers a certain
      solipsistic trend inimical to the role of the other and of the acceptance of
      innovation this entails has come to hold sway. This situation can in his view be
      overcome by the introduction of new applications and practices, as in the past
      with the acceptance of Klein's ideas in the field of child analysis. Theory is in
      the author's opinion always the product of clinical practice in our field, a
      thesis he illustrates by an account of his own work with couples and families,
      where the patient is deemed to be not any one individual in the group but the
      group itself considered as a nexus of links. The implications and theoretical
      repercussions of this link-based conception are discussed at length and some
      novel terms are introduced--for example, the link between subjects, imposition,
      the social subject, the subject relationship and the multiple subject. Alienness
      and the 'other', and presence and absence, are shown to be important concepts and
      are distinguished from object relations. The author concludes with a reference to
      a new resistance, namely to linking, and its implications in relation both to
      personality and to phenomena such as ethnic and religious conflict.

PMID- 11234106
TI  - From the fundamental rule to the analysing situation.
AB  - The analytic method relies on the mental capacity to produce an associative
      sequence, and, afterwards, to discern its unconscious logic; within the social
      practice of the analytic cure, the method presents itself as the mastered
      enactment of the condition through which free association proves to be possible,
      interpretable and beneficial. There is a contradiction between the necessity of
      relying on a former theorisation and that of willingly suspending a knowledge
      that might serve the authenticity of the experience. The author reminds us of the
      structural links between the fundamental rule and the defined situations within
      which the analytic process of transformative investigation can take place. He
      raises the problems that it is suggested arise with the initial objectivation
      method by acknowledging the transference as the created-found object of
      interpretation. He shows how the transformation of the patient into analysand
      implies the functional introjection of the various elements contained by the
      analytic site. The meaning given to the expression 'analysing situation' is made
      explicit. The crucial value of the process of enunciation is illustrated by a
      brief example.

PMID- 11234108
TI  - The countertransference scene in France.

PMID- 11234110
TI  - On Feldman's 'Some views on the manifestations of the death instinct in clinical
      work'.

PMID- 11234109
TI  - On Steiner's 'Containment, enactment and communication'.

PMID- 11234111
TI  - Ohtsuki Kenji and the beginnings of lay analysis in Japan.
AB  - The authors outline the major role played by Ohtsuki Kenji in the formation of
      the Japanese Psychoanalytic Society. Unlike the other pioneers of psychoanalysis
      in Japan, Ohtsuki never went abroad or met Freud. He was a literature graduate
      who taught himself the fundamentals of psychoanalysis. He organised the
      translation of Freud's complete works, formed a psychoanalytic training institute
      and started a journal that carried English-language editorials. These became the
      major means whereby foreign analysts came to know and understand the Japanese
      psychoanalytic scene. A number of rival groups amalgamated to form the Japanese
      Psychoanalytical Association in the mid-fifties, excluding Ohtsuki's group
      despite its pre-war prominence. The authors reconsider Ohtsuki's role in the
      light of his many articles, his autobiography, new information uncovered in
      interviews conducted with current analysts and with Ohtsuki's widow and son. They
      describe his championing of lay analysis, and his criticisms of medicalisation of
      the discipline and of the view from abroad that questioned the suitability of
      Japanese culture for psychoanalytic therapy, as well as his efforts to modify
      some of the basic tenets of psychoanalysis to accord with his own views in his
      later work.

PMID- 11234112
TI  - The birth of psychoanalysis from the spirit of technique.
AB  - The author aims to demonstrate, through a textual analysis of Freud's work, how
      the creation of psychoanalysis as a plausible set of understandings of the human
      mind has a methodological origin that has sometimes been overlooked: in the Greek
      concept of techne. Freud, an acknowledged pupil of Brentano, was well versed in
      Aristotelian rhetoric, and selected this instrument of investigation, dependent
      on language, from the outset of his efforts to describe, understand and treat the
      world of the unconscious mind. Working in the tradition of techne Freud actually
      rehabilitated 'guessing' (zu erraten)--although it became a largely overlooked
      concept in Freud's work--and so sought to place conjectural reason as the
      definitive form of knowledge for the investigation and treatment of the mind.
      This explains why the 1895 'Project' could not succeed and why technique became
      irreplaceable as the via regia in 'The Interpretation of Dreams'. Its model is
      founded in Aristotelian rhetoric, whose conception of language was first
      rediscovered by Nietzsche and was used therapeutically by Freud. Freud's view is
      apparent in his 1923 definition of psychoanalysis which is compared to the
      current IPA definition, a definition which, the author suggests, gives a
      misleading prominence to 'theory' and which shows how far a questionable
      rationality has removed conjectural reason from the field, to its detriment. From
      this point of view it is argued that the 'precious conjunction' (Freud) between
      investigation and treatment has been abandoned, and the concept of historical
      truth and its significance for psychoanalysis obscured.

PMID- 11234113
TI  - Loving them to death: the anorexic and her objects.
AB  - The author suggests that eating disorders function to reinforce phantasies of
      control of the internal parents, a feature of Klein's view of the manic defence.
      Using this hypothesis, she attempts to differentiate between anorexia and
      bulimia. It is argued that in anorexia objects are felt to be permanently in
      thrall, suspended or frozen, whereas in bulimia they are attacked in a frenzied
      and intermittent way. Using case material from three seriously ill patients, the
      author draws attention to some important differences between them. Two of the
      patients were treated in psychoanalysis, while the third was seen for an extended
      consultation and once-weekly treatment thereafter. It is suggested that the
      nature and degree of the murderous attack on the internal couple may determine
      the severity of the illness as well as the patient's capacity to benefit from
      treatment. The conclusions drawn are discussed in relation to some contemporary
      views on eating disorders as well as writings on the difficulties of working
      through the Oedipus complex more generally. The author suggests that eating
      disorders may represent a special case of oedipal illusions.

PMID- 11234114
TI  - The training analysis at a time when theory is in short supply.
AB  - The author discusses the risks confronting the training analysis when original
      theoretical production is lacking. In his view, little progress has been made
      since Freud's time in establishing a general science of the psyche based on
      Freud's interpretive method. What has been transmitted is stated to be not
      Freud's method of discovery but the knowledge thereby produced, which has been
      handed down in the form of doctrines, defined as theory presented as psychic
      fact. Hence analyses tend to apply theories rather than to discover unconscious.
      Some of today's most common interpretational aberrations are described, and the
      author shows the powerful suggestive effect on patients of using doctrines as
      metaphors of psychic life. Where such a training analysis is reinforced by a like
      form of theoretical teaching and supervision, candidates may uncritically
      assimilate the relevant theory. The author uses his concept of the reality
      providing circuit to show how belief in a doctrine imparted by the training
      analysis makes that doctrine appear as the ideological basis of psychoanalytic
      knowledge. He finally notes that, theories being essentially heuristic
      instruments and not bodies of acquired information, the consequence of the
      current dearth of theories, which have degenerated into doctrines, is that the
      training analysis itself has come to constitute the theory of training in many
      institutes.

PMID- 11234115
TI  - Supervision: a container-contained approach.
AB  - The authors illustrate an approach to the supervisory process as a learning
      experience for both supervisee and supervisor built on the containment of
      unconscious anxieties. It is argued that a core function of psychoanalytic
      supervision is to help contain the emotional turbulence and the unconscious
      anxieties arising and evolving in the two interacting domains of the analytic and
      the supervisory sessions. From this perspective, the analyst-patient interaction
      and that of the supervisee and supervisor can be understood as twin, tiered
      transformational arenas, the supervisory one being at the service of holding and
      grasping the roles the supervisee/analyst goes through as part of the analytic
      process. On the basis of detailed clinical material from a disturbed 7-year-old
      girl, the authors explore the interrelated issues and difficulties in containing
      anxieties and turbulence in both the analytic and the supervisory situation. When
      emotional containment is adequately handled, the supervision helps the
      understanding and development of the supervisee's use of his/her own personality
      as a treatment instrument, as advocated by Fleming and Benedek decades ago. The
      supervisory session thus furthers the resolution of clinical issues through
      symbol-formation, clinical sessions and supervision being twin domains for
      recording and understanding emotional evolution.

PMID- 11234116
TI  - The psychoanalyst and the baby: a new look at work with infants.
AB  - The author argues that objections to involving the infant in a relationship with
      an analyst have led psychoanalysts to overlook the possibility that the
      interaction between the infant and the analyst may be able to activate and
      retrieve those parts of the infant's inner world that have been excluded from
      containment and be conductive to a vitalisation of the emotional disturbance that
      can then become worked through in the mother-infant relationship. As long as the
      infant's ego is weak, the infant and the mother have a unique flexibility that
      enables them to repair disturbances in their relationship when the emotional
      container-contained link is (re-)established. Based on the assumptions (1) that a
      relationship can be established between the infant and the analyst, (2) that the
      infant has a primordial subjectivity and self as base for intersubjectivity and
      the search for containment, (3) that the infant has an unique flexibility in
      changing representations of itself and others that comes to an end as the ego
      develops, and (4) that the infant is able to process aspects of language, three
      cases, at the ages of 6, 18 and 20 months, are presented to illustrate what is
      considered to be a novel approach to work with infants.

PMID- 11234117
TI  - This bulb's for you.

PMID- 11234118
TI  - Kinder, gentler clinics. Fed up with the care of your HMO? Try your local
      hospital for massage, acupuncture and aromatherapy.

PMID- 11234119
TI  - DARE checks into rehab.

PMID- 11234120
TI  - Showdown in the DNA corral.

PMID- 11234121
TI  - Attention, doctors.

PMID- 11234122
TI  - Truth or D.A.R.E. A new drug course.

PMID- 11234123
TI  - After the breakthrough. It will take years to turn genetic data into drugs.

PMID- 11234124
TI  - Fusion adds spice, maybe substance, to workouts.

PMID- 11234125
TI  - Vitamins: swallow hard before taking.

PMID- 11234126
TI  - Mighty morphin' materials management.

PMID- 11234127
TI  - Labor intensive.

PMID- 11234128
TI  - Five letters spell success.

PMID- 11234129
TI  - Follow that wheelchair--then clean it!

PMID- 11234130
TI  - Stats. Managed care loses its edge.

PMID- 11234131
TI  - [Epidemiology of ischemic heart disease and characteristics of atherosclerosis in
      male residents in Yakutsk].
AB  - AIM: To study trends in prevalence, risk factors (RF) and mortality of ischemic
      heart disease (IHD), contribution of RF to risk of death due to IHD and other
      cardiovascular diseases (CVD) among male population of Yakutsk; to determine
      characteristics of atherosclerosis among native male population and migrants.
      MATERIAL AND METHODS: A clinicopathological epidemiological trial covered male
      population of Yakutsk. It was performed by standard techniques within the scope
      of the cooperative program. RESULTS: The analysis of the trends for the last 10
      years demonstrates a marked rise in the incidence rates of arterial hypertension
      (AH), overweight and hypercholesterolemia. CVD mortality reached 38.4% of overall
      mortality. Such factors as AH, smoking, IHD, ischemic ECG changes and overweight
      contribute much to the integral risk of CVD death. A comparative morphometric
      analysis of atherosclerosis development in 1965-1968 and 1985-1988 showed
      accelerated development of atherosclerosis both among native population and
      migrants in 1985-1988. There are population differences in development of
      atherosclerosis in males from native population and migrants. The effects of
      trace elements on formation of atherosclerosis components in the Far North were
      evaluated. CONCLUSION: Present-day epidemiological situation in relation to IHD
      and other CVD necessitates further monitoring of the situation, activation of
      primary and secondary IHD prevention among population of the Far North.

PMID- 11234132
TI  - [Results of the one-stage screening for ischemic heart disease in the Tumen
      population sample].
AB  - AIM: To study prevalence of ischemic heart disease (IHD) in free living
      population of Tumen. MATERIAL AND METHODS: A one-stage cardiological screening
      covered 1608 Tumen residents (70.3% of the respondents of the mail questionnaire
      survey). IHD was stated by the standard methods. RESULTS: IHD incidence among
      male and female population of Tumen was rather high. Angina of effort was found
      in 4.5% of males and 5.1% of females, painless IHD was detected in 3.2 and 3.7%
      of male and female 55-64-year-old population, respectively, by extended criteria.
      IHD incidence rate by the extended criteria reached 12.5%. CONCLUSION: Primary
      results of the survey indicate that Tumen population is at high risk of
      cardiovascular diseases. This fact requires a detailed analysis of the trends in
      IHD prevalence in a prospective study.

PMID- 11234133
TI  - [Arterial pressure mean values and distribution, and relation to duration of
      residence in the North in school children living in the north of Tumen region].
AB  - AIM: To elicit regularities significant for epidemiological situation by arterial
      hypertension among schoolchildren of Tumen North with reference to duration of
      living in the North. MATERIAL AND METHODS: 2525 schoolchildren (the response
      85.3%) aged 7-15 years entered a one-stage epidemiological study. RESULTS: Tables
      were made of arterial pressure distribution in the schoolchildren population. The
      pressure was higher in children living in the North for more than 5 years.
      Arterial hypertension was registered in 12.7% of the examinees (14.1% of boys and
      11.6% of girls). CONCLUSION: Prevalence of arterial hypertension in
      schoolchildren living in the North was high. A correlation was found between mean
      arterial pressure and duration of the exposure to North conditions.

PMID- 11234134
TI  - [Acute coronary events in female residents of Tomsk. Results of 5-year
      observation (1994-1998)].
AB  - AIM: To study epidemiology of acute coronary conditions (ACC) including acute
      myocardial infarction (AMI) and acute coronary failure (ACF) among female
      population of Tomsk aged over 20 years and trends for 5 years. MATERIAL AND
      METHODS: 1919 ACC episodes were compared in the women: 1616(84.2%) cases of AMI
      and 303(15.8%) cases of ACF. The comparison concerned epidemiological indices:
      morbidity, hospital and prehospital ACC lethality, the disease history,
      pathomorphological evidence. RESULTS: ACC prevalence among women for 5 years
      remained at the level 2.0-2.2 cases per 1000 women of the same age. Number of ACC
      patients with progressive angina decreased while number of cases of cardiogenic
      shock went up in paralled decrease of the number of episodes of acute left
      ventricular failure, arrhythmia and abnormal conduction. AMI as macrofocal
      occurred more frequently, ACC hospital lethality rose (due to more cases in
      patients over 60). Autopsy showed more cases of stenosing atherosclerosis of
      coronary arteries. CONCLUSION: No changes for the better occurred for 5 years
      among female population of Tomsk in relation to ACC incidence and mortality. This
      necessitates introduction of measures of effective primary and secondary
      prevention of ischemic heart disease and arterial hypertension.

PMID- 11234135
TI  - [Relations between ankylosing spondyloarthritis and HLA-B27 in various ethnic
      groups in Russia].
AB  - AIM: To characterize relationship between prevalence of ankylosing
      spondylarthritis (ASA) and incidence rate of HLA-B27 in genotypically different
      ethnic groups of Russia with interpolation of the results to other populations.
      MATERIAL AND METHODS: 2287 individuals from genotypically different ethnic groups
      were examined in overall one-stage epidemiological trial. RESULTS: Prevalence of
      ASA in ethnic groups ranged from 0.2 to 2.0% while occurrence of HLA0B27--from 15
      to 40%. Rate of correlation between the disease prevalence and incidence of B27
      was 0.82. The equation for calculation of ASA incidence rate by HLA-B27 incidence
      was devised: AC(%) = -0.40 + 0.06x. CONCLUSION: In most world populations
      prevalence of ASA correlates with population frequency HLA-B27 though in some
      ethnic groups this correlation is absent. Consequently, ASA is genetically
      heterogenous.

PMID- 11234136
TI  - [Prevalence and risk factors of the lower back syndrome in automobile drivers].
AB  - AIM: To study epidemiology of low spine pain syndrome (LSPS) in drivers of
      municipal transport; to specify factors stimulating its onset. MATERIAL AND
      METHODS: 600 drivers from Orenburg were screened for LSPS. Risk factors were
      evaluated in two groups of patients: 130 drivers with LSPS and 130 matched
      controls free of LSPS. The data obtained were entered to a standard
      questionnaire, risk factors were considered according to working place
      attestation. RESULTS: Low spine pain complaints were registered in each 1-2
      drivers of three. Those having the pain were as a rule 30-50-year-olds with
      service duration more than 10 years. They had pain for more than 5 years. 94.6%
      of them had acute pain. Spinal function was restricted in most of the examined
      LSPS drivers. Major risk factors of LSPS were the following: toxic substances,
      static loads, physical overstrain, draughts. A relationship was found between
      intensive smoking, alcohol abuse, low physical activity and LSPS onset.
      CONCLUSION: High prevalence of LSPS, frequent exacerbations, impaired spinal
      function cause a high disability rate. Thus, LSPS is an important medicosocial
      problem.

PMID- 11234137
TI  - [Plants sterols and stanols: new prospects in prevention of ischemic heart
      disease (based on data published in the European Heart Journal, 1999, vol. 1
      (Suppl S))].

PMID- 11234138
TI  - [Comparison of carvedilol and atenolol efficacy in patients with stable effort
      angina].
AB  - AIM: To compare effectiveness of carvedilol--beta-adrenoblocker with vasodilating
      action--with atenolol which is beta-adrenoblocker having no vasodilating activity
      in coronary heart disease (CHD) patients with stable effort angina. MATERIAL AND
      METHODS: The trial entered 28 CHD patients with a history of myocardial
      infarction (MI). All the patients had no contraindications to beta
      adrenoblockers, had positive exercise tolerance test. After the control period of
      7-10 days the patients received either carvedilol (14 patients) or atenolol (14
      patients) in a mean daily dose 20.5 mg (6.25 to 50 mg) and 25.9 mg (12.5 to 100
      mg), respectively, twice a day. The course of the treatment took 4 weeks. The
      effect was evaluated at treadmill exercise test. RESULTS: Both drugs diminished
      heart rate, carvedilol was less effective in this respect. Both drugs
      significantly prolonged time of exercise to the anginal attack and ST depression
      by 1.0 mm. Side effects arose in 6 and 4 patients, respectively. CONCLUSION:
      Carvedilol and atenolol are equally effective in the treatment of stable effort
      angina.

PMID- 11234139
TI  - [Five-year activity of new departments of emergency cardiological care with
      cardiac resuscitation units in Moscow].
AB  - AIM: To analyse results of treatment in new cardiological critical care units in
      Moscow (62 beds). MATERIAL AND METHODS: Five years reports presented in 1993-1999
      to Moscow Public Health Committee. RESULTS: The activity of the new cardiological
      units proved efficient: cardiovascular lethality reduced by 20%; quality of
      diagnosis and treatment improved; bed turnover increased. CONCLUSION: A new
      system of medical care for critical cardiological patients is recommended for
      introduction as basic form of organization of urgent cardiological inpatient care
      in Moscow.

PMID- 11234140
TI  - [Circular disorders in the common carotid artery bed and associated
      psychovegetative and hemodynamic disturbances in hypertensive patients].
AB  - AIM: To specify circulatory disorders in the bed of common carotid artery (CCA)
      in hypertensive patients and these disorders influence on psychovegetative and
      hemodynamic disturbances. MATERIAL AND METHODS: Ultrasonic dopplerography of the
      region of common carotid artery, ECG, examinations of central hemodynamics,
      vegetative regulation of cardiac rhythm and psychic status were performed in 200
      patients with arterial hypertension (AH). RESULTS: AH patients with unaffected
      CCA circulation have common central and cerebral hemodynamics, hyperkinetic
      circulation, retain psychovegetative adaptation. Left ventricular myocardial
      hypertrophy is absent. In impaired elasticity and tonicity of the vascular wall
      there was hypokinetic circulation, left ventricular hypertrophy,
      anxiohypochondria in high sympathetic activity. In stenotic CCA the patients have
      hypokinetic circulation, left ventricular hypertrophy and dilation and resultant
      asthenodepressive disorders and vegetative dystonia. CONCLUSION: Aggravation of
      cerebrovascular insufficiency goes in parallel with AH progression and arterial
      atherosclerosis. Changes of circulation variant, left ventricular cardiodynamic
      rearrangement are accompanied with changes in psychovegetative homeostasis.

PMID- 11234141
TI  - [Clinical efficacy of carvedilol in patients with severe cardiac insufficiency].
AB  - AIM: To assess clinical response to carvedilol in long-term treatment of cardiac
      failure (CF). MATERIAL AND METHODS: 34 patients with CF (NYHA functional class
      III-IV) were observed for 6 months. 25 of them received standard therapy combined
      with carvedilol, 9 patients received only standard therapy. RESULTS: Carvedilol
      produced positive changes in the disease functional class, left ventricular
      ejection fraction, stabilisation of echo-CG parameters and cardiothoracic index,
      resulted in prolongation of 6-min walk distance. Discontinuation of carvedilol
      therapy enhances CF symptoms. CONCLUSION: Long-term therapy with carvedilol
      inhibits CF progression.

PMID- 11234142
TI  - [Effective treatment of cardiac failure with caposide at an outpatient clinic].
AB  - AIM: To evaluate results of long-term outpatient use of caposide in patients with
      cardiac failure. MATERIAL AND METHODS: 74 patients (59 males and 15 females aged
      40-76 years) with chronic cardiac failure (CCF) received caposide in individual
      doses. CCF was caused by ischemic heart disease (IHD) and dilated cardiomyopathy
      in 65 and 9 patients, respectively. The treatment effect was assessed by changes
      in clinical symptoms, quality of life and physical activity. RESULTS: Clinical
      symptoms, functional class of IHD, exercise tolerance and quality of life
      improved. Serious side effects were absent. CONCLUSION: Caposide can be
      considered as first-line therapy in outpatient treatment of patients with CCF of
      different severity as monotherapy and adjuvant in combined treatment.

PMID- 11234143
TI  - [Virus-specific antibodies and interferon therapy in chronic hepatitis C].
AB  - AIM: To study the spectrum of antibodies in chronic hepatitis C (CHC) against
      various antigenic structures of hepatitis C virus (HCV) and changes in their
      quantity in response to interferon treatment. MATERIAL AND METHODS: Enzyme
      immunoassays (kits by Diagnostic Systems, N. Novgorod) were used in examination
      of 144 CHC patients with circulation of HCV antibodies in peripheral blood.
      RESULTS: IgG antibodies to cor, NS3, NS4 HCV antigens were present in the highest
      percentage (75-100%) and concentration (2.5-1.9 units). IgM antibodies to cor
      HCV, IgM and IgG to HS5 HCV were detected in 36-63%, concentration of the
      antibodies ranged 0.7-1.7 units. Interferon therapy reduced frequency and amount
      of virus-specific antibodies to various antigenic structures of HCV, primarily
      IgM to cor, NS5-HCV, anti-IgG NS5-HCV. CONCLUSION: In CHC a wide spectrum of
      antibodies to HCV antigenic structures are produced. They have different
      biological properties. Interferon treatment diminished their frequency and
      amount. This allows to consider changes in the amount of virus-specific
      antibodies in CHC as a criterion of antiviral treatment effectiveness.

PMID- 11234144
TI  - [Outcomes of the long-term treatment with a novel mucolytic drug pulmozin in
      mucoviscidosis patients].
AB  - AIM: To study clinical effectiveness and safety of a new mucolytic drug pulmozim
      (Switzerland) adjuvant to basic therapy in mucoviscidosis patients of different
      age in Russia. MATERIAL AND METHODS: 15 patients with mucoviscidosis aged 5-36
      years, functional lung capacity and FEV-1 at least 40% received pulmozim for 30
      days. The drug was given in a single daily dose 2.5 mg in inhalations. The study
      included three stages: initial 14 days--discontinuation of all mucolytic drugs,
      30-day course of pulmozim, 14-day follow-up without pulmozim and other
      mucolytics. RESULTS: Pulmozim in the above regimen was effective in patients with
      mixed and moderate mucoviscidosis. The drug facilitates respiration, improves
      sputum rheology, normalizes general condition of the patient, is simple for use,
      has good organoleptic properties. CONCLUSION: Pulmozim is an effective mucolytic
      drug in combined treatment of mucoviscidosis.

PMID- 11234145
TI  - [Preventive cardiology: educational problems].

PMID- 11234146
TI  - [Modern principles in antihypertensive therapy].

PMID- 11234147
TI  - [Actual problems in the emergency cardiological care at the prehospital stage].

PMID- 11234148
TI  - [Chronic pancreatitis].

PMID- 11234149
TI  - [Medicine at the edge of the new century: illusions and realities.

PMID- 11234150
TI  - [The role of unfavorable social and psychological factors in the onset and course
      of diabetes mellitus].

PMID- 11234151
TI  - [Late cutaneous porphyria and systemic lupus erythematosus (brief literature
      review and analysis of own data)].

PMID- 11234153
TI  - Providing culturally appropriate care. A tale of two hospitals.

PMID- 11234152
TI  - [Detection and prevalence of risk factors to develop chronic noninfectious
      diseases in the organized population group in West Siberia].
AB  - AIM: To study prevalence of factors of risk to develop chronic noninfectious
      diseases (CNID) in the population of railroad men of the West Siberia and these
      factors association with ischemic heart disease (IHD) and cerebrovascular
      disorders. MATERIAL AND METHODS: A one-stage sample epidemiological survey of
      CNID risk factors enrolled 10,677 railroad men of West Siberia aged 20-65 years.
      The risk factors were: arterial hypertension (AH), smoking, hypercholesterolemia
      (HCE), obesity, low physical activity (LPA), impaired flucose tolerance (IGT).
      RESULTS: High incidence of AH, HCE, smoking, obesity, LPA, IGT as well as
      nutritional shift to food rich in fat was found. The results of the regression
      multivariate analysis show that such factors as AH, HCE and smoking are
      associated with and contribute much to high risk of IHD; AH, severe HCE and
      obesity contribute to high risk of cerebral pathology. CONCLUSION: Further
      studies are needed of CNID prevalence among railroad men. Measures of primary
      multifactor prevention should be designed and introduced to correct the above
      risk factors.

PMID- 11234154
TI  - Mirroring your community: a good reflection on you.

PMID- 11234155
TI  - Procuring capital equipment.

PMID- 11234156
TI  - The benefits of being a mentor.

PMID- 11234157
TI  - New approaches to executive compensation.

PMID- 11234158
TI  - The value of grass-roots action.

PMID- 11234160
TI  - Interview with ACHE's incoming chairman.

PMID- 11234159
TI  - Navigating differences in patient values.

PMID- 11234161
TI  - Retaining employees: lessons from the best.

PMID- 11234163
TI  - What's cookin'? In cafeteria makeovers, it's a mix of savvy traffic patterns,
      easy care, good looks.

PMID- 11234162
TI  - Effective customer service practices.

PMID- 11234164
TI  - Juggling act. Another ball in the air for facility managers: assessing medical
      office space.

PMID- 11234165
TI  - Health care highlights. NFPA's fall meeting tackles health facility issues.

PMID- 11234166
TI  - Team spirit. Four steps to cleaning success.

PMID- 11234168
TI  - A critical tool or potential trouble? 'Data warehouse' could hold health info on
      35 million Americans.

PMID- 11234169
TI  - Putting the patient first. Sentara's successful integration leads to top spot in
      annual ranking.

PMID- 11234167
TI  - Taking care of business. Hospital groups push members hard for financial data to
      use with feds.

PMID- 11234170
TI  - Nurse shortage predicted. HHS study says profession must find way to attract,
      retain recruits.

PMID- 11234171
TI  - Buyer beware. Software can aid HIPAA compliance, but providers must weigh
      vendors' claims.

PMID- 11234172
TI  - The pet GPO. No, we're not talking about imaging; this one is for dogs, cats and
      horses ... and vets like it, too.

PMID- 11234173
TI  - Pickings aplenty. Investor-owned chains are scooping up struggling not-for
      profits.

PMID- 11234174
TI  - Bankruptcy court a deals-happening place.

PMID- 11234175
TI  - Toward full disclosure. As healthcare bond issuers face more troubles, pressure
      mounts for more information sharing with investors.

PMID- 11234176
TI  - Sharing their views. Faith-based systems use stockholder role to promote social
      change.

PMID- 11234177
TI  - Banishing white blood cells. Safety group urges FDA to adopt new rules for
      prefiltering blood.

PMID- 11234178
TI  - Web survey. January survey results: a look at the National Practitioner Data
      Bank.

PMID- 11234179
TI  - Staffing outlook grim. High turnover expected to continue in skilled nursing,
      assisted living.

PMID- 11234180
TI  - Decision support and the appropriate use of fibrinolysis in myocardial
      infarction.
AB  - CONTEXT: For patients with suspected acute myocardial infarction, decisions about
      fibrinolytic therapy must account for trade-offs between risks and benefits,
      which vary according to the clinical characteristics of the patient. OBJECTIVE:
      To assess whether use of a decision-support computer program (DSCP) improves the
      selection of appropriate candidates for fibrinolytic therapy among patients with
      suspected acute myocardial infarction. DESIGN: Before-and-after trial at a small
      rural hospital in Ireland. INTERVENTION: DSCP based on a previously published
      decision-analysis model. With input of patient characteristics (e.g., age, sex,
      duration of symptoms, findings on electrocardiography) at initial evaluation, the
      DSCP predicts the likelihood of different outcomes (e.g., mortality, stroke) and
      life expectancy with and without fibrinolysis. PATIENTS: 894 consecutive patients
      (262 before DSCP was introduced, 632 after) admitted to the coronary care unit
      with suspected acute myocardial infarction between January 1993 and July 1999.
      OUTCOME MEASURES: Proportion of appropriate candidates (ST-segment elevation > 2
      mm on electrocardiogram, symptom duration < or = 6 hours) receiving fibrinolysis
      before and after implementation of DSCP. RESULTS: In general, patients admitted
      before and after DSCP implementation had similar clinical characteristics. The
      preintervention group presented somewhat earlier after the onset of symptoms (5.4
      hours for preintervention vs. 7.2 hours for postintervention; P < 0.01) but had
      fewer confirmed acute myocardial infarctions (32% vs. 38%; P = 0.13). The
      proportion of appropriate patients receiving fibrinolysis before and after DSCP
      was nearly identical (66.7% vs. 68.9%; P > 0.2). Patients who received
      fibrinolysis after implementation of DSCP tended to be older (66.7 years vs. 63.8
      years; P = 0.11) and were more likely to be female (36% vs. 26%; P > 0.2) than
      those who received fibrinolysis before DSCP implementation. The door-to-needle
      time decreased significantly from 88 minutes to 67 minutes after implementation
      of DSCP (P < 0.01). CONCLUSION: Although overall rates of fibrinolysis did not
      change after implementation of DSCP, fibrinolytics may have been more
      appropriately directed toward higher risk patients who may be more likely to
      benefit from them.

PMID- 11234181
TI  - Colorectal cancer screening in Massachusetts: measuring compliance with current
      guidelines.
AB  - CONTEXT: Professional organizations have published guidelines for colorectal
      cancer screening. Defining which patients are currently, or should be, screened
      is an important clinical and public health issue. OBJECTIVE: To document the
      prevalence of colorectal cancer screening and profile the tests patients have
      had. DESIGN/POPULATION: A random-digit telephone survey of Massachusetts adults,
      50 years of age and older. OUTCOME MEASURES: Percentage of persons ever and
      currently tested by fecal occult blood tests, flexible sigmoidoscopy, barium
      enema, colonoscopy, or some combination of these tests. RESULTS: Sixty-five
      percent of those contacted agreed to the telephone interview. Approximately 29%
      of the 1119 respondents had never had any currently accepted test, including 10%
      who reported having only a fecal occult blood test done in a provider's office
      and 19% who reported having no tests. At least 51% were currently tested by one
      or more tests for screening, diagnosis, or both. Another 10% were possibly
      current by colonoscopy or barium enema, both of which can be ordered for
      screening but are more commonly used to evaluate a problem, such as rectal
      bleeding, or for surveillance after identification of a polyp or other
      abnormality. An additional 11% had been tested at some point but were not current
      according to guidelines. CONCLUSIONS: Accurate assessment of rates of colorectal
      cancer screening is complex because of the multiple acceptable screening methods,
      the fact that patients may be tested for screening or diagnostic purposes, and
      the lack of adequate systems for tracking such testing. For accurate measurement,
      all methods must be assessed regardless of whether tests were ordered for
      screening, diagnosis, or surveillance.

PMID- 11234182
TI  - Randomized trial of fructosamine home monitoring in patients with diabetes.
AB  - CONTEXT: Recognition of the importance of glycemic control in type 2 diabetes has
      generated interest in developing ways to improve such control. Levels of
      fructosamine, 1-amino-1-deoxyfructose, are highly correlated with those of
      hemoglobin A1c (HbA1c) and can be monitored in the home. DESIGN: Randomized
      trial. PARTICIPANTS: 140 adult patients with HbA1c values of 8% or greater were
      recruited to the trial through referral from physicians and a direct mailing to
      potentially eligible persons. INTERVENTION: Weekly home fructosamine monitoring
      in addition to daily glucose monitoring. Control patients monitored daily glucose
      only. Both groups of patients were contacted regularly by telephone and were
      given the same instructions on diet and exercise. OUTCOME: Measures of glycemic
      control 3 and 6 months after randomization. RESULTS: No significant difference
      was found between the two groups in the mean absolute decrease of HbA1c levels at
      3 months (0.5% in the fructosamine group vs. 0.8% in the control group; P > 0.2),
      and the difference favored the control group at 6 months (0.7% fructosamine vs.
      1.2% control; P = 0.04). Both groups had a statistically significant improvement
      in glycemic control. CONCLUSIONS: The addition of home fructosamine monitoring to
      routine glucose monitoring did not improve glycemic control.

PMID- 11234183
TI  - How effective is the computer-based clinical practice guideline?
AB  - CONTEXT: The primary prevention of coronary artery disease in patients with
      diabetes could have a large impact on health care costs and outcomes. Guidelines
      for improving diabetic health indices are common, but significant challenges
      exist in implementing them. GENERAL QUESTION: How does integrating an evidence
      based guideline into an electronic medical record affect patient care? SPECIFIC
      RESEARCH CHALLENGE: How can we implement the new guideline-enhanced medical
      record in a controlled manner and measure its impact on physician satisfaction,
      diabetes process measures, and the risk for cardiovascular disease? PROPOSED
      APPROACH: All patients in the University of Washington system have an electronic
      Web-based medical record. Patients with diabetes will be randomly assigned to a
      guideline-enhanced or standard electronic medical record. The electronic medical
      record allows measurement of most clinical process measures and outcomes.
      Physician satisfaction will be measured by survey. POTENTIAL DIFFICULTIES:
      Contamination may occur when guideline recommendations are applied to control
      patients as physicians gain experience with the guideline-enhanced record.

PMID- 11234184
TI  - Computer-based decision support: wishing on a star?

PMID- 11234185
TI  - Colorectal cancer screening: keeping the options open.

PMID- 11234186
TI  - Primer on group randomized trials..

PMID- 11234187
TI  - The productivity of small animal species in small-scale mixed farming systems in
      subtropical Bolivia.
AB  - The productivity of the scavenging, small animal species (chickens, ducks, pigs,
      hair sheep and guinea-pigs) commonly found on small-scale farms at the forest
      margin in subtropical Bolivia was monitored over a full year. Chickens and guinea
      pigs were kept mainly for home consumption, while ducks and pigs were kept mainly
      for sale. Sheep served both purposes, depending upon the family requirements. In
      the absence of veterinary treatment, the productivity varied greatly between
      farms. Pigs gave the greatest gross return, but received the largest amount of
      supplementary feed. Under the existing system, chickens, ducks and sheep all gave
      similar gross returns per breeding female, although chickens produced good
      returns and made a large contribution to the family diet where the reproductive
      efficiency was high and the chick mortality was low. Mortality resulting from
      disease was a major problem in poultry, while internal parasites appeared to be
      important limiting factors in pigs and sheep. Guinea-pigs showed no major
      problems apart from theft, and were an important dietary component for immigrant
      families from the highlands of the country. Small animal species have largely
      been ignored by agricultural research and development activities in Bolivia and
      elsewhere. They currently make significant contributions to the livelihoods of
      poor people in terms of both income and food security, and this could be greatly
      increased by simple improvements in animal husbandry.

PMID- 11234188
TI  - An abattoir survey on the frequency of fatty liver syndrome in dairy cows from
      the suburbs of Tehran.
AB  - One hundred and six Holstein and Holstein x native cows were inspected before and
      after slaughter, and liver samples were taken. The fat content of all the liver
      samples was estimated by an extraction method (Soxhlet). The livers of 29 cows
      (27%) were classified as fatty. Seventeen of the animals were newly calved, 47
      were non-pregnant, 33 were pregnant and 9 were dry, the median values for the fat
      content of their livers being 60.6, 34.4, 34.7 and 33.8 mg/g, respectively. The
      median concentration of liver fat in the first group was significantly different
      from that in each of the other groups (p < 0.01).

PMID- 11234189
TI  - Contagious bovine pleuropneumonia in Tanzania: current status.
AB  - CBPP reappeared in Arusha, Northern Tanzania in 1990, having been introduced from
      Kenya. The disease spread rapidly to Mara region through rustling of sick or
      infected animals. In November 1992, an unrelated outbreak occurred in Kagera,
      having spread from Southern Uganda. Up to the end of December 1994, the disease
      appeared to be confined to Kagera and Arusha. In January 1995, CBPP was observed
      in Morogoro region, south of the central railway line. Thereafter, the disease
      spread through western Tanzania. More recently, further disease has occurred in
      the Southern Highlands and Central regions. The contaminated area now stretches
      roughly between latitudes 1 degree and 9 degrees S and longitudes 30 degrees and
      37 degrees E, with a cattle population of about 10 million. The direct losses
      incurred as a result of animal mortality, and vaccination campaign and disease
      surveillance costs have been assessed at over US$11 million. Indirect losses
      resulting from chronic disease are much more difficult to assess but are believed
      to be even higher. Control of the disease has been through restricting animal
      movements and a mass vaccination campaign. Uncontrolled animal movement during
      transhumance, trade, cattle thefts and vaccination breakthroughs facilitated the
      spread of the disease.

PMID- 11234191
TI  - Technical communication. Implications of the liberalization of veterinary drug
      marketing in Ghana.

PMID- 11234190
TI  - Comparison of cryoprotectants in the preservation of Theileria parva sporozoites
      using an in vitro infectivity assay.
AB  - An in vitro infectivity assay was used to examine five cryoprotectants for their
      suitability for preserving Theileria parva sporozoites. All five were capable of
      preserving T. parva sporozoites through freezing, the optimal concentrations
      being 7.5% for glycerol, 5% for dimethyl sulphoxide (DMSO), poly
      (vinylpyrrolidone) (PVP) and poly(ethylene glycol) (PEG), and 2.5% for
      hydroxyethyl starch (HES). When the five cryoprotectants were compared at their
      optimal concentrations, using a modification of the standard method of stabilate
      preparation, glycerol was significantly better than the others (p < 0.05).
      Measurement of the effects of each cryoprotectant on the osmolality of the media
      revealed that glycerol and DMSO elevated the osmolality significantly (p < 0.05).
      Resuscitation of glycerol-preserved sporozoites required the presence of glycerol
      in the diluent to maintain infectivity. Studies on the effects of equilibration
      time in glycerol on the infectivity of sporozoites showed that those frozen
      immediately after mixing (2 min) were as infective as those frozen after 60 min
      of equilibration.

PMID- 11234192
TI  - Effect of replacing cotton seed cake with poultry droppings on weight gain of
      growing cattle at Bambui, Cameroon.
AB  - To investigate the effect of replacing cotton seed cake by poultry droppings in
      the diet of cattle, 30 animals were randomly allocated to three dietary
      treatments in a 2 x 3 factorial design, sex x treatments. The three treatments
      consisted of replacing 0%, 25% and 50% (T0, T25, T50 respectively) of the crude
      protein in 500 g of cotton seed cake with an equivalent amount of protein in
      poultry droppings. The concentrate offered was 615 g in T0, 652.5 g in T25 and
      690 g in T50 per animal per day. After an adaptation period of 14 days, followed
      by 65 days of the experiment, the intake of concentrate and the average daily
      weight gains were recorded. There was no significant difference (p > 0.05) in the
      concentrate intake or average daily weight gain of bulls subjected to the three
      treatments. However, heifers tended to grow more slowly on T50 compared to T0 (p
      < 0.05), though the difference in their intake of concentrate was not significant
      (p > 0.05). Although T50 (47% inclusion in total concentrate), was less
      palatable, it seemed to have increased forage intake from pasture. These results
      suggest that poultry droppings can effectively substitute cotton seed cake in the
      diets of suckler cattle.

PMID- 11234193
TI  - Condensed tannin and saponin content of Vigna unguiculata (L.) Walp, Desmodium
      uncinatum, Stylosanthes guianensis and Stylosanthes scabra grown in Zimbabwe.
AB  - Samples of the tropical forage legumes Vigna unguiculata (L.) Walp (cowpea),
      Desmodium uncinatum (silverleaf desmodium), Stylosanthes guianensis (oxley fine
      stem stylo) and Stylosanthes scabra (fitzroy) and of natural pasture (veld) hay
      were analysed and ranked according to their proanthocyanidin (PA) and saponin
      content. Silverleaf desmodium and fitzroy leaf and stem samples of different ages
      were also separately analysed for the PA contents. All the samples analysed
      contained some PA but no saponins. High levels of PA were detected in silverleaf
      desmodium and very low levels in veld hay and cowpea. In all samples, more of the
      tannins were bound to protein or neutral detergent fibre (NDF) than were
      extractable, most being bound to proteins. The proportion of the unextractable PA
      was greater in younger than in mature materials.

PMID- 11234194
TI  - Reproductive performance and milk production of Damascus goats fed acacia shrubs
      or berseem clover hay in North Sinai, Egypt.
AB  - Thirty-three adult Damascus does (29 +/- 1.1 kg BW) were fed 0.6 kg per head per
      day of a concentrate diet plus ad libitum rice straw (Oryza sativa, control, R),
      or green acacia (Acacia saligna, A) or berseem clover hay (Trifolium
      alexandrinum, B). All treatment groups had free access to underground saline
      water containing 3600 ppm TDS. The DM intake was lower (p < 0.05) for the R group
      but did not differ between the other two groups. The DM intake of acacia was 0.64
      kg per head per day (1.98% BW) during pregnancy and 0.93 kg per head per day
      (2.95% BW) during lactation. The drinking water differed (p < 0.05) between the
      three dietary treatments; group B had the highest mean intake and group A had the
      lowest. The percentage kidding and the litter weight at birth did not differ
      significantly between the groups. However, the number of kids weaned/doe kidding
      and the weight of the kids weaned/doe kidding were significantly higher for group
      B. The mean body weight of the kids at birth and at weaning were significantly
      lower for group R. The total milk yield over 10 weeks and the milk composition
      (total solids, fat and protein percentages) were significantly different between
      the three groups; group B having the highest means and group R the lowest. These
      results suggest that supplemental feeding is required to enhance the productivity
      of goats in arid or semi-arid environments and Acacia saligna should not be used
      fresh in excessive quantities for extended periods.

PMID- 11234195
TI  - Whiplash.

PMID- 11234196
TI  - Whiplash.

PMID- 11234197
TI  - Practice counsellors.

PMID- 11234198
TI  - The Lords' report on complementary/alternative medicine: something for everyone.

PMID- 11234199
TI  - Genetic testing and insurance.

PMID- 11234200
TI  - Coronary artery disease--from bench to bedside.

PMID- 11234201
TI  - Diabetes mellitus in the young.

PMID- 11234202
TI  - Trichobezoar.

PMID- 11234203
TI  - Is job insecurity harmful to health?

PMID- 11234204
TI  - Cover arrangements for consultants on leave: an analysis of job descriptions.
AB  - There is much ambiguity about consultant leave allowances and arrangements for
      cover in the National Health Service. We analysed job descriptions for 47
      consultant posts advertised in mid-2000. 35 defined a duty rota but only 3
      mentioned specific available leave (all different). In 32 there was no mention of
      cover for colleagues on leave. When a consultant is absent, colleagues tend to
      provide cover for emergency cases but not for elective admissions, which are
      managed largely by junior doctors. This arrangement is particularly hazardous in
      surgical specialties. If elective surgery is to continue when the consultant is
      absent, arrangements for leave and cover need to be more clearly defined.

PMID- 11234205
TI  - Training in oral medicine.
AB  - 88 members of the UK specialty society of oral medicine were asked about career
      satisfaction and their views on training programmes. 70% responded (79% of
      consultants and all accredited trainees). Men work longer hours than women,
      report less control over their work and experience more stress. Although high
      work satisfaction is reported, nearly one-third regret their choice of specialty.
      Men more than women do locum work while training. Most respondents would welcome
      flexible training, job shares, financial support during training and a mentoring
      scheme.

PMID- 11234206
TI  - Psychotic depression after a fall.

PMID- 11234207
TI  - Pel-Ebstein fever with cyclical pancytopenia.

PMID- 11234208
TI  - A child with pyrexia, flank pain and hip symptoms.

PMID- 11234209
TI  - Primary Staphylococcus aureus meningitis in an infant.

PMID- 11234210
TI  - Colo-broncho-cutaneous fistula complicating traumatic diaphragmatic rupture.

PMID- 11234211
TI  - Spontaneous oesophageal perforation during vaginal delivery.

PMID- 11234212
TI  - Painful eye after a 'flu-like illness.

PMID- 11234213
TI  - Did Tay miss the case?

PMID- 11234214
TI  - Influence of diarrhoeal disease on military and naval campaigns.

PMID- 11234215
TI  - Collaboration on research picks up steam.

PMID- 11234216
TI  - Allopathic medicine gone awry.

PMID- 11234217
TI  - Thoracic lymphatic pumping and the efficacy of influenza vaccination in healthy
      young and elderly populations.
AB  - The authors investigated whether thoracic lymphatic pumping (TLP) after FluShield
      vaccination enhanced the production of anti-influenza immunoglobulins in elderly
      individuals, who are at particular risk for influenza. Osteopathic students and
      non-TLP-treated elderly subjects served as controls. Serum antibody titers were
      quantified with enzyme-linked immunosorbent assay, and hemagglutination
      inhibition assay, both of which generated comparable results. While approximately
      70% of the younger controls had increased anti-influenza immunoglobulin
      production on vaccination, only 30% to 35% of the aged population had increased
      antibody production. There was no significant enhancement in anti-influenza
      immunoglobulin production in the TLP-treated subjects. The authors' findings
      suggest that TLP in conjunction with influenza vaccination does not enhance
      immunization against influenza in otherwise healthy and active populations.
      However, such techniques may be of value when applied in conjunction with
      vaccination to nonambulatory patients or on actual influenza exposure of at-risk
      individuals.

PMID- 11234218
TI  - Testing osteopathic medical school graduates for licensure: is COMLEX-USA the
      most appropriate examination?
AB  - Osteopathic and allopathic physicians receive authority to practice medicine
      through the licensing boards of the states in which they practice. Each state has
      the responsibility to operate a licensing board for physicians and other medical
      professionals. These boards choose which examinations are acceptable to establish
      that a physician is licensable to practice medicine. The National Board of
      Osteopathic Medical Examiners (NBOME) administers the Comprehensive Osteopathic
      Medical Licensing Examination (COMLEX-USA). To determine the views of the
      educational leaders of the osteopathic profession regarding licensure testing, a
      survey was mailed to leaders in the profession. Of the 799 surveys mailed, 341
      (43%) were returned. Respondents were asked 19 questions, using a Likert scale to
      record responses (strongly disagree, 1; strongly agree, 5). Eighty-eight percent
      of respondents believed that osteopathic medicine is a distinct profession.
      Seventy percent of respondents felt that COMLEX-USA is the standard for testing
      osteopathic trainees, while 70% believed trainees should continue to be tested by
      a unique process. According to 72% of the respondents, the NBOME, through its
      testing procedures, continues to be the organization best suited to test the
      knowledge of osteopathic students and graduates. These results indicate that
      among the practicing leadership of the osteopathic profession, overwhelming
      support exists for the profession to retain the ability and the right to examine
      its own trainees from within.

PMID- 11234219
TI  - Osteopathy in its early adulthood, 1945-1955.

PMID- 11234220
TI  - [Combination effect of teicoplanin and beta-lactams on MRSA].
AB  - In vitro combination effect of teicoplanin and beta-lactams was investigated
      against 109 MRSA strains isolated from a variety of clinical specimens at the
      Social Health Insurance Medical Center during the period from January 1994
      through February 2000. TEIC + panipenem (PAPM) was revealed by microbroth
      dilution method-based checkerboard method, to exhibit synergistic effect of min.
      FIC index < or = 0.5 against all the 109 strains. The combination of TEIC and
      flomoxef (FMOX) was shown to have synergistic effect on 108 strains (99.1%). The
      combination of TEIC and cefepime (CFPM) was shown to have synergistic effect on
      96 strains (88.1%). The combination of TEIC and cefmetazole (CMZ) was shown to
      have synergistic effect on all the 109 strains (100%). The mean value of min. FIC
      indices obtained from each of the combinations was 0.1259 as to TEIC + PAPM,
      0.2019 as to TEIC + FMOX, 0.3257 as to TEIC + CFPM and 0.1995 as to TEIC + CMZ,
      in other words, the combination of TEIC + PAPM showed the lowest value of all the
      combinations. While MIC80 was 2.0 micrograms/ml when TEIC was used alone, it was
      < or = 0.06 microgram/ml when used together with PAPM, and 0.13 microgram/ml when
      used together with FMOX, respectively. While MIC80 was 3.2 micrograms/ml when
      PAPM was used alone, it was 0.5 microgram/ml when used together with TEIC.
      Meanwhile, the value for FMOX was changed from > or = 128 micrograms/ml to 4.0
      micrograms/ml. When TEIC was used in combination with CFPM, MIC80 was found to be
      0.5 microgram/ml. Similar to the case of the concurrent use with FMOX, the value
      obtained by combination with CMZ was 0.13 microgram/ml. While MIC80 was 128
      micrograms/ml when CFPM was used alone, it was 8.0 micrograms/ml when used
      together with TEIC, whereas the value for CMZ was decreased from 64 micrograms/ml
      to 2.0 micrograms/ml. In conclusion, TEIC's antibacterial activity was shown to
      be accentuated by any of the combinations.

PMID- 11234221
TI  - [The frequency of Streptococcus pneumoniae strains and sensitivity surveillance
      for several antibiotics in Gifu Prefecture].
AB  - The frequency and the antibacterial sensitivity of Streptococcus pneumoniae
      strains isolated from 6 key hospitals (in 5 areas) and 1 otorhinolaryngology
      clinic in Gifu Prefecture from February to March, 1999, were investigated with
      several antibiotics. A total of 128 strains of Streptococcus pneumoniae were
      isolated throughout the study: 47 strains (36.7%) of penicillin-susceptible S.
      pneumoniae (PSSP), 51 strains (39.8%) of penicillin-intermediate S. pneumoniae
      (PISP), and 30 strains (23.4%) of penicillin-resistant S. pneumoniae (PRSP); the
      resistant bacteria being relatively prominent. In these hospitals, PSSP was
      isolated by 38.8% in all the key hospitals and by 30% in the otolaryngology
      clinic with almost no discernible difference. PISP was isolated by 63.3%, higher
      in the otolaryngology clinic and PRSP by 28.6%, higher in the key hospitals
      conversely. The MIC90s in PISP and PRSP were determined with the antibiotics. In
      result, only cefditoren (CDTR) showed favorable antibacterial activities with the
      MIC90 of 0.78 microgram/ml among penicillins or oral cephems. The MIC90s of
      carbapenems such as imipenem (IPM), meropenem (MEPM), and panipenem (PAPM) were
      less than 0.39 microgram/ml; particularly, PAPM showed the highest antibacterial
      activities. Among new quinolones such as tosufloxacin (TFLX), levofloxacin
      (LVFX), sparfloxacin (SPFX), and ciprofloxacin (CPFX), TFLX showed the highest
      antibacterial activities with the MIC90 of 0.39 microgram/ml. Other agents showed
      very low antibacterial activities as the MIC90s were 25 micrograms/ml in
      minocycline (MINO) and more than 100 micrograms/ml in clarithromycin (CAM) and
      clindamycin (CLDM).

PMID- 11234222
TI  - Nephrotoxicity of teicoplanin in rats.
AB  - Teicoplanin, a glycopeptide antibiotic, is marketed in a number of European
      countries and has recently been put on the market in Japan. The spectrum of
      antibacterial activity of teicoplanin is equivalent or superior to that of
      vancomycin. The aim of the present study is to examine the nephrotoxicity of
      teicoplanin compared with vancomycin in rats. Wistar male rats, housed in a light
      controlled room at room temperature for 1 week, were used. They were injected
      with either 15 or 50 mg/kg/day of teicoplanin or 50 or 200 mg/kg/day of
      vancomycin at 13:00 daily for 14 days. The rats were randomly assigned to groups
      of five rats each and were housed individually in metabolic cages to collect
      urine. Urine samples were collected 24 hours prior to the drug treatment and
      every 24 hours thereafter for 14 days. N-Acetyl-beta-D-glucosaminidase (NAG)
      activity was determined in the supernatant and expressed in international units
      per total urine collected for 24 hours. The group which was given vancomycin 200
      mg/kg/day had significantly elevated urinary NAG levels compared with the other
      groups (p < 0.05). No significant differences were observed in the NAG levels in
      urine among the remaining three groups. These results suggest that the
      nephrotoxicity of teicoplanin may be only one-fourth that of vancomycin in rats.
      It appears that by extrapolating the dose amount required for the treatment in
      humans to rats, the high dose of teicoplanin was set at 50 mg/kg/day and that of
      vancomycin, 200 mg/kg/day. The recommended dose for teicoplanin will probably be
      200 mg/day compared to 2 g/day of vancomycin. If the teicoplanin dose is only one
      tenth that of the vancomycin dose, then teicoplanin should be better tolerated
      than vancomycin in terms of nephrotoxicity.

PMID- 11234224
TI  - Thanks to Medicare, Humana posts profit.

PMID- 11234223
TI  - [Evaluation of antibiotics by the method of initial bactericidal activity].
AB  - Minimum inhibitory concentration (MIC) has been generally used to evaluate the
      activity of antimicrobial agents. However, there is some discrepancy between
      clinical efficacy and the MIC value. We studied the relationship between initial
      bactericidal activity of imipenem (IPM), panipenem (PAPM), meropenem (MEPM),
      ceftazidime (CAZ) and amikacin (AMK) and the respective MIC values against
      Pseudomonas aeruginosa PAO1. Initial bactericidal activity was defined as percent
      reduction of initial bacterial cell concentration (10(6) cells/ml) after 1 hour
      incubation following addition of antibiotic. The concentration of antibiotic used
      in this experiment was the blood level of each antibiotic at 3 hours after
      administration by drip infusion of the usual dose (IPM, PAPM and CAZ were 1 g for
      1 hour drip infusion, MEPM was 1 g for 0.5 hours drip infusion and AMK was 200 mg
      for 1 hour drip infusion, respectively). The antibiotic concentration of IPM,
      PAPM, MEPM, CAZ and AMK were 8.77 micrograms/ml, 6.37 micrograms/ml, 4.12
      micrograms/ml, 12.0 micrograms/ml and 5.18 micrograms/ml, respectively. MICs of
      IPM, PAPM, MEPM, CAZ and AMK were 2 micrograms/ml, 64 micrograms/ml, 1
      microgram/ml, 1 microgram/ml and 2 micrograms/ml, respectively. Initial
      bactericidal activity of IPM, PAPM, MEPM, and CAZ against P. aeruginosa PAO1 was
      98.2%, 86.1%, 48.1%, and 43.4% reduction in bacterial concentration,
      respectively. AMK shows the strongest initial bactericidal activity with more
      than 99.9%. The killing speed of IPM was obviously the most rapid among the three
      carbapenems. The MIC of PAPM was significantly higher than the other antibiotics,
      and the initial bactericidal activity of PAPM was second to IPM. We can classify
      antibiotics into two groups based on initial bactericidal activity against P.
      aeruginosa; one class is antibiotics having rapid initial killing such as AMK,
      IPM and PAPM, the other is CAZ, MEPM showing slow initial killing.

PMID- 11234225
TI  - Wanting a piece of the pie. Hospitals latching onto new issues to justify bids
      for federal dollars.

PMID- 11234226
TI  - Acutely aware. HCA to buy second acute-care hospital in U.S. since strategic
      overhaul.

PMID- 11234227
TI  - Proposed mergers cause stir in Minn. Groups fear loss of reproductive services if
      hospitals merge with Catholic providers.

PMID- 11234228
TI  - Setting priorities. HIMSS survey: complying with HIPAA is main concern of
      healthcare pros.

PMID- 11234229
TI  - Health Care Hall of Fame. A voice unsilenced. Bays built healthcare legacy on
      foundation of tireless innovation.

PMID- 11234230
TI  - Health Care Hall of Fame. Forging a standard. Visionary approach to hospital
      strategies led Hicks to the forefront.

PMID- 11234231
TI  - Health Care Hall of Fame. Speaking plainly, a real leader. Sigmond made
      reputation by straight-shooting as hospital planner.

PMID- 11234232
TI  - CHW (Catholic Healthcare West) pulls in the reins. Reorganization plan
      centralizes management; 350 execs to lose jobs.

PMID- 11234233
TI  - From consumer line to hospital chain. New for-profit company SunLink to
      concentrate on rural markets.

PMID- 11234235
TI  - Stars, money and medical crusades.

PMID- 11234234
TI  - The new war on Parkinson's.

PMID- 11234236
TI  - Fading of the light. The eye disease AMD is currently incurable, but you can take
      steps to manage it.

PMID- 11234237
TI  - Facing death on your own terms.

PMID- 11234238
TI  - Binge eating disorder: a review of the literature after publication of DSM-IV.
AB  - Binge eating disorder (BED) is a syndrome marked by recurrent episodes of binge
      eating, in the absence of the regular use of inappropriate compensatory
      behaviors. Since the inclusion of BED in DSM-IV as a Diagnostic Category in Need
      of Further Research, a great deal of research has been conducted. This paper
      reviews research on BED since publication of DSM-IV in 1994. We conclude that
      questions about the definition of BED persist. Furthermore, recent studies which
      have strictly used the DSM-IV definition of BED have found that the full syndrome
      is found in less than 3% of obese adults seeking weight loss treatment and occurs
      in less than 1% of the general adult population. Binge eating is a common symptom
      associated with obesity, however. BED may be conceptualized as a psychiatric
      syndrome or it may be viewed as a behavioral symptom associated with obesity. We
      conclude that clarification of this conceptual issue is needed if research on BED
      is to progress.

PMID- 11234239
TI  - Anxiety, depression, hunger and body composition: III. Their relationships in
      obese patients.
AB  - The present paper explores the relationships between anxiety, depression, hunger
      sensation and body composition in obese patients (OP). The aim is to detect
      whether or not there are abnormalities in these relationships in OP as compared
      to clinically healthy subjects (CHS). The study was performed on 22 CHS (2 M, 20
      W; mean age = 24 +/- 2 years; mean body mass index = 21 +/- 2 kg/m2) and 48 OP (4
      M, 44 W; mean age = 40 +/- 17 years; mean body mass index = 32 +/- 7 kg/m2).
      Anxiety and depression were found to be correlated, negatively, with the relative
      lean body mass, and, positively, with the fat body mass in OP but not in CHS.
      These findings corroborate the idea that anxiety and depression can reach an
      abnormal expression when obesity shows its worst loss in lean body mass and its
      highest expansion in adipocyte mass. As hunger sensation was found not to
      correlate with either anxiety or depression in OP, the opinion is expressed that
      the impairment of anxio-depressive integrity is a corollary of obesity rather
      than a primary affective disorder leading to obesity via an enhanced food intake.

PMID- 11234240
TI  - Obsessive-compulsive symptoms as a correlate of severity in the clinical
      presentation of eating disorders: measuring the effects of depression.
AB  - Obsessive-compulsive symptoms have been related to severity in the clinical
      presentation of eating disorders, whereas the impact of depression on the
      correlations between their severity and the severity of eating disorders has not
      been investigated. This paper assesses the effects of depression in 42 adolescent
      patients who met DSM-IV criteria for anorexia nervosa or bulimia nervosa by using
      the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the Eating Disorder Inventory
      (EDI) and the Beck Depression Inventory (BDI). The results indicate that patients
      who show elevated obsessionality and compulsivity on the Y-BOCS display a
      significantly higher degree of disturbed attitudes and behaviours concerning
      eating than patients with limited obsessionality and compulsivity. However, when
      the effects of depression are considered, all the differences found disappear.
      Our study suggests that depression is more directly associated with the severity
      of eating disorders than obsessive-compulsive symptoms and that the intensity of
      obsessive-compulsive symptoms in eating disorders is influenced by the intensity
      of depression. The relations between obsessive-compulsive symptoms, depression
      and eating disorders are not known. Even so this study highlights the importance
      of assessing depression when using obsessive and compulsive symptoms as a
      correlate of severity in the clinical presentation of eating disorders.

PMID- 11234241
TI  - The effect of high-fat diet on the development of obesity and serum leptin level
      in rats.
AB  - Ten male Wistar-albino rats were overfed with high-fat diet (margarine at the
      dose 40 g/kg body weight/day in addition to standard rat diet) during six months
      from the age of between 8-12 weeks. Ten male rats received a standard chow for
      the same period. The body weights of the overfed rats increased time dependently
      (basal 171.5 +/- 5, at sixth month 268 +/- 19 g), whereas those of the rats fed
      with standard chow did not increase significantly (basal 177 +/- 6.4, at sixth
      month 220 +/- 10 g). At the sixth month, mean body fat percentages were 36.3 +/-
      6.7% and 24.2 +/- 5.4% respectively. Both total cholesterol-triglyceride levels
      and mean serum leptin levels were also higher than in the overfed rats (p < 0.01
      and p < 0.05 respectively). The livers of all rats were histopathologically
      normal. CONCLUSION: High-fat diet resulting in an increased body fat percentage
      in rats is associated with hyperleptinemia, hypercholesterolemia and
      hypertriglyceridemia.

PMID- 11234242
TI  - A case of iodine-induced hypothyroidism in a patient with anorexia nervosa.

PMID- 11234243
TI  - Empowerment of women with purging-type bulimia nervosa through nutritional
      rehabilitation.
AB  - Since the primary role of psychoeducation in eating disorders is to act as a
      foundation for other interventions, nutritional rehabilitation should use the
      same therapeutic principles as psychotherapy. This paper looks at the possibility
      that traditional psychoeducational results can be enhanced in patients with
      bulimia nervosa by a new nutritional rehabilitation programme focused on
      psychobiological reorganization of eating behaviour as opposed to the
      prescription of regular eating patterns. Forty women with purging-type bulimia
      nervosa were enrolled for a 24-week experimental period of cognitive-behavioural
      psychotherapy (CBT) and were randomly and evenly divided into two groups to
      follow a psychobiological nutritional rehabilitation (PNR) and a traditional
      nutritional rehabilitation (TNR) programme respectively. The follow-up period
      averaged 6 months; four subjects dropped out. The baselines of both groups were
      comparable with regard to key features, including binge and vomiting frequency,
      and carbohydrate and lipid intake. Both groups improved significantly over time,
      though improvements in bingeing and vomiting and lipid intake were greater in the
      PNR group (p < 0.001), both at the end of the study and at the follow-up. This
      psychobiological approach to appetite and weight control may constitute a
      theoretical framework facilitating the application of cognitive-behavioural
      guidelines to both nutritional rehabilitation and psychotherapy.

PMID- 11234244
TI  - Multidimensionality in adolescent eating problems. A two-phase measurement study.
AB  - The aims of this study were, firstly, to examine the factor structure of single
      items from several self-report methods used to measure eating disorder symptoms,
      and secondly, in search for a short assessment instrument to reduce the number of
      items within each factor. Factor analyses were employed to identify and confirm
      the constructs measured by a total of sixty items drawn from these assessment
      methods. In phase one, 508 secondary school pupils were recruited as subjects,
      and principal factor analysis identified three factors; body concern, dieting,
      and loss of control over eating. Twenty-nine items were retained, and in phase
      two subjected to a second data collection among 4129 secondary school pupils.
      Confirmatory factor analysis was employed to cross-validate the factor structure
      from phase one. The three-factor structure was confirmed satisfactorily for boys,
      but not for girls aged 12-14 years. For girls aged 14-16 years, it was confirmed
      when a number of items were omitted. The findings are discussed in relation to
      restraint theory and the continuum hypothesis.

PMID- 11234245
TI  - Gender differences among those exhibiting characteristics of binge eating
      disorder.
AB  - One hundred and eighty-seven former residential weight control participants
      exhibiting binge eating traits were assessed for gender differences regarding
      demographics, diet, exercise, weight control techniques, behavior modification
      techniques and binge eating characteristics. Data were gathered using a 68-item
      paper pencil questionnaire. Results indicate that there were no significant
      differences between males and females regarding demographic variables, and the
      number and types of weight control programs tried since leaving the residential
      program. Significant differences did exist between males and females in the
      number of times they had started dieting in the past year. No significant
      differences were observed among males and females regarding severity, binge
      emotions and compensatory behaviors. Statistically significant differences did
      exist regarding post-binge emotions. Results from this study suggest that males
      and females differ in regard to the diet/binge cycle and additionally, males
      appear to have a different or less emotional response subsequent to a binge.

PMID- 11234246
TI  - Daily hunger sensation and body compartments: II. Their relationships in obese
      patients.
AB  - Hunger sensation (HS) is a signal whose levels change during the 24-h day. The
      daily mean level of HS was correlated with the human body compartments, as
      investigated by bioelectrical impedance analysis, to detect the relationship
      between the orectic perception and both the free fat mass (FFM) and the fat body
      mass (FBM) in 22 clinically healthy subjects (CHS) (2 M, 20 W, BMI: 18.5-24.0
      kg/m2) and 48 obese patients (OP) (4 M, 44 W, BMI: 25.2-54.7 kg/m2). In CHS, the
      daily mean level of HS correlated positively with the FFM and negatively with the
      FBM. These correlations were not present in OP. This lack of relationships
      between HS and the body compartments where energy is maximally consumed (i.e.,
      the FFM) and maximally stored (i.e., the FBM) indicates that the orectic response
      to energy expenditure and the orectic inhibition to fat accumulation are feedback
      mechanisms which are impaired in obesity.

PMID- 11234248
TI  - Irene, a case study of a bulimia nervosa patient: the therapeutic process of
      integrative painting therapy.
AB  - The bulimic symptomatology--supposedly an expression of certain developments in
      our society--increased immensely. The progress of Integrative Painting Therapy
      applied to a bulimia nervosa patient, is simultaneously visible and documented.
      This gives insight into the psychodynamics and psychopathology of this disorder,
      as well as its development during treatment. The painting group provides a quick
      access to the patient's emotions and it permits the establishment of a strong
      therapeutic relationship. Paintings generated within the group reflect a
      patient's inner experiences and provide a starting-point for the therapeutic
      process. In her pictures, Irene confronts her bulimia disorder and is finally
      able to come to terms with her social role as a woman, her growing up and her
      longing for a healthy family background especially meaning contact with her
      father. In this spirally evolving process, where painting groups, single and
      family therapy work together, she was finally able to break free from her bulimic
      symptoms and find a new access to herself and her family, especially her father.

PMID- 11234247
TI  - Eating Attitudes Test and culture: a study in northern and southern Italy.
AB  - The EAT (Eating Attitudes Test) has been widely used to compare eating morbidity
      in cultural groups and variations in it have been taken as indicative of cultural
      differences. This study assumed the existence of cultural differences between the
      north and the south of Italy. The EAT scores of female students from a northern
      and a southern Italian high school were compared. They were both higher than in
      other European studies, though there were no significant differences between the
      two groups. The result could be due to sampling limitations, but could also
      indicate that the EAT is not a reliable yardstick of cultural differences.

PMID- 11234249
TI  - Outpatient group therapy for anorexia nervosa: a preliminary study.
AB  - Group therapy is generally recognized as an important form of psychotherapy for
      anorexia nervosa patients, but there are few controlled studies of its
      effectiveness. The aim of the current study was to determine the effectiveness of
      cognitive-behavioural therapy (CBT) for the treatment of anorexia nervosa in
      outpatients. Twenty-six outpatients with anorexia nervosa, were assessed for
      depression (BDI, Beck Depression Inventory), eating psychopathology (EDI, Eating
      Disorders Inventory), eating attitudes (EAT, Eating Attitudes Test) and weight at
      the beginning and at the end of the treatment and at one year follow-up. Our
      results substantiate the effectiveness of the CBT approach as a treatment and
      also at one year follow-up. Good EAT scores were observed in 70% of our cases
      after the treatment and in 60% at follow-up. Further research should assess the
      effectiveness of therapeutic groups more intensively because of their economic
      advantages.

PMID- 11234250
TI  - Gender differences in colour naming performance for gender specific body shape
      images.
AB  - Males are increasingly subjected to pressures to conform to aesthetic body
      stereotypes. There is, however, comparatively little published research on the
      aetiology of male body shape concerns. Two experiments are presented, which
      investigate the relationship between gender specific body shape concerns and
      colour-naming performance. Each study comprised a between subject design, in
      which each subject was tested on a single occasion. A pictorial version of a
      modified Stroop task was used in both studies. Subjects colour-named gender
      specific obese and thin body shape images and semantically homogeneous neutral
      images (birds) presented in a blocked format. The first experiment investigated
      female subjects (N = 68) and the second investigated males (N = 56). Subjects
      also completed a self-report measure of eating behaviour. Currently dieting
      female subjects exhibited significant colour-naming differences between obese and
      neutral images. A similar pattern of colour-naming performance was found to be
      related to external eating in the male subjects.

PMID- 11234251
TI  - Use of the Parental Bonding Instrument to compare interpretations of the parental
      bond by adolescent girls with restricting and binge/purging anorexia nervosa.
AB  - The Parental Bonding Instrument (PBI) was administered to 62 adolescent female
      patients (mean age 14.3): 35 with restricting-type anorexia nervosa (RAN), and 27
      with binge/purging-type anorexia nervosa (B/PAN) according to the DSM-IV
      criteria, all at onset and initial diagnosis. The PBI was also administered to a
      control group (55 subjects) and 22 patients with Crohn's disease or celiac
      disease. The three groups were matched for age and socioeconomic status. The RAN
      and B/PAN patients gave significantly different interpretations of the parental
      bond (PB): for the former, it was adequate with both parents, for the latter it
      was inadequate, especially with the father. The fact that these differences exist
      at the onset of anorexia prior to any possible effect of therapy suggests that
      its structure is determined by different family dynamics.

PMID- 11234252
TI  - Eating pattern and self-esteem in overweight women.
AB  - Recent studies have shown that the relationship between poor self-esteem and
      disturbed eating patterns may be more fully understood when the self-esteem
      concept is divided into an affective domain ('self-liking') and a cognitive
      domain ('self-competence'). In the present study 38 overweight women between the
      ages of 21 and 68 participated in an 8-week weight reduction program whereby the
      Self-Liking and Competence Scale [SLCS] and the Eating Disorder Scale [EDS-5]
      were used in order to measure self-esteem and eating patterns, respectively. An
      improvement in the eating patterns corresponded to an improvement in self-liking,
      but not in self-competence. Statistically significant weight reduction did occur,
      but on the average, the subjects still remained overweight. As in other studies
      on normal weight individuals in analogous test situations completing the same
      instruments, the results point only to a specific relationship between disturbed
      eating patterns and self-liking. The results suggest that an increased benefit
      from a weight reduction program could be expected if strategies for improving
      eating patterns and self-liking are included. This hypothesis warrants further
      controlled treatment studies.

PMID- 11234253
TI  - Comorbidity of obsessive compulsive disorder in patients with eating disorders.
AB  - OBJECTIVE: We investigated the prevalence of obsessive compulsive disorder (OCD)
      among patients with eating disorders (ED). METHOD: 66 female inpatients who met
      the DSM-IV criteria for anorexia nervosa (AN) or bulimia nervosa (BN)
      participated in the study. The Structured Clinical Interview for DSM III-R
      diagnoses (SCID), the Eating Disorder Inventory (EDI), the revised 90-item
      Symptom-Checklist (SCL-90-R), the Beck Depression Inventory (BDI), and the
      Toronto Alexithymia Scale (TAS-20) were carried out. RESULTS: Twelve patients
      (18.2%) met the DSM-III-R criteria for lifetime OCD: 7 had a current OCD and 5
      had a past history of OCD. These patients had significantly higher (more
      pathological) mean scores on the EDI and the SCL-90-R total scales. Analyses of
      the EDI subscales revealed significantly higher scores for ineffectiveness,
      perfectionism, interoceptive awareness, and maturity fears. As expected, analyses
      of the SCL-90-R subscales revealed significantly higher scores for OCD. In
      addition, there was a trend towards higher somatization scores in patients with
      comorbid OCD. We could not find any significant differences in the BDI and the
      TAS total scores. In addition, patients with comorbid OCD showed a significantly
      higher lifetime prevalence of bipolar disorder, simple phobia, and somatoform
      disorders. DISCUSSION: Our results confirm previous reports of a strong
      association between ED and OCD and suggest that the prevalence of OCD may be
      correlated with a higher severity of the eating disorder and general
      psychopathological parameters.

PMID- 11234254
TI  - Personal experience with laparoscopic adjustable silicone gastric banding in the
      treatment of morbid obesity.
AB  - The treatment of 162 pathologically obese patients by means of laparoscopic
      adjustable silicone gastric banding (LASGB) is described: 112 patients were
      followed up for 15 months. All patients had a positive outcome, as documented by
      the progressive reduction in their body mass index (BMI) from an initial mean +/-
      SD of 42.6 +/- 8.5 to 32.2 +/- 9 after 15 months. Only 11 complications were
      encountered. The mean hospital stay was 2 days. These findings support the notion
      that LASGB is a safe and effective technique for the treatment of morbid obesity.

PMID- 11234255
TI  - Acarbose treatment in obesity: a controlled study.
AB  - Acarbose is an alpha-glucosidase inhibitor which reversibly inhibits
      oligosaccharidase and disaccharidase at the brush border of the small intestine.
      The aim of this study was to observe its effectiveness in the treatment of
      obesity. METHODS: Two groups of 25 obese women were put on a 15 kcal/kg/day low
      calorie diet for 12 weeks. One group (the study group) received 150 mg/day
      acarbose for the first 2 weeks and 300 mg/day acarbose for the remaining 10
      weeks. The second group (controls) received no additional treatment. Body weight,
      BMI, skinfold thickness, serum lipids, OGTT, and insulin and C-peptide responses
      to OGTT were assessed before and after the study. RESULTS: Body weight, BMI and
      skinfold thickness decreased significantly in both groups. Basal insulin and
      triglyceride levels in the study group, total and LDL cholesterol and
      triglyceride levels in the control group decreased significantly. No difference
      was found between the two groups when these decrements were compared, but the
      triglyceride level fell more in the control group. CONCLUSION: Additional
      acarbose therapy is not more beneficial than low-calorie diet therapy alone.

PMID- 11234256
TI  - Iodine-induced hypothyroidism as a result of excessive intake of confectionery
      made with tangle weed, Kombu, used as a low calorie food during a bulimic period
      in a patient with anorexia nervosa.
AB  - A 20-year-old Japanese female anorectic patient developed primary hypothyroidism
      associated with generalized edema because of excessive daily intake (40 to 50 g)
      of confectionery made with tangle weed, Kombu, which she substituted to food
      during bulimic periods; TSH 60.35 mcU/ml, free T3 1.19 pg/ml, and free T4 0.48
      ng/dl, and her weight increased by 12 kg to 45 kg over 4 months. After withdrawal
      of Kombu her thyroid function returned to normal, and her weight decreased by 7
      kg to 38 kg along with disappearance of edema. In conclusion, the physician
      noticed that susceptible anorectic patients may sometime develop hypothyroidism
      or hyperthyroidism because of excessive iodine intake of sea-weed confectionery
      as a substitute of high calorie cakes during bulimic period.

PMID- 11234258
TI  - [Transluminal balloon angioplasty in patients with multivessel lesion of the
      coronary bed].

PMID- 11234257
TI  - Association of dietary restraint and disinhibition with eating behavior, body
      mass, and hunger.
AB  - This study investigated the association of dietary restraint and disinhibition
      with self-reported and actual eating behavior, body mass, and hunger. A sample of
      124 women were categorized into one of four groups based upon high and low scores
      on measures of Dietary Restraint and Disinhibition using the Three Factor Eating
      Questionnaire. Half of the participants in each group consumed a high sugar/high
      fat chocolate pudding as a dietary preload. All participants were given a meal
      comprised of a standard macaroni and beef product. The interaction of Dietary
      Restraint and Disinhibition was related to differences in body mass. The Dietary
      Restraint factor was related to self-reported pathological eating behavior and
      influenced both perceived hunger and subjective hunger ratings. However, actual
      eating behavior measured by calories consumed and rate of intake was unrelated to
      the Dietary Restraint factor. Disinhibition was associated with excessive eating,
      an increased rate of eating, self-reports of eating disorder symptomatology, and
      perceived hunger. Hence, actual eating behavior was significantly influenced by
      the ingestive motivational factor, Disinhibition, but not by the cognitive
      factor, Dietary Restraint. These data also suggest that the Disinhibition
      construct is measuring overeating rather than disinhibited eating which implies
      the disruption of Dietary Restraint.

PMID- 11234259
TI  - [Changes in aortic elasticity in aged patients with essential arterial
      hypertension].
AB  - Aortic elasticity was studied in aged patients with mild and moderate arterial
      hypertension using magnetic resonance imaging. The analysis of changes in cross
      section area (CSA) of the ascending aorta in systole has shown that in some
      patients maximal CSA occurs in different systolic phases while in the other
      patients CSA remains unchanged. Calculation with the elasticity rate proved that
      patients with maximal aortic diameter at the beginning of the systole have
      maximal aortic elasticity while those with minimal changes in aortic diameter in
      the course of the systole have minimal elasticity. Thus, in aged patients with
      mild and moderate essential hypertension aortic wall loses its elasticity to
      different extent. Further studies will specify clinical and pathogenetic
      implications of reduced aortic elasticity in arterial hypertension.

PMID- 11234260
TI  - [Clinical, diagnostic and therapeutic features of tricuspid infectious
      endocarditis].
AB  - From 1987 to 1998, examination and treatment were conducted of 12 patients with
      infectious endocarditis of the tricuspid valve (TIE). 11 of them were operated.
      TIE was clinically characterized by lesser circulation thromboembolism and marked
      right ventricular failure. TIE was successfully diagnosed by echo-CG (diagnostic
      sensitivity 83.3%). Serious disturbances of cellular immunity demanded
      immunocorrection. Indications for surgical treatment are listed.

PMID- 11234261
TI  - [The quality of life in patients with cardiac syndrome X].
AB  - Quality of life in patients with cardiological syndrome X (XS) and ischemic heart
      disease (IHD) assessed with Nottingham Health Profile questionnaire was compared
      to that shown by exercise tests. Compared to IHD patients, those with XS have
      worse quality of life. This is explained by a lower pain threshold and,
      consequently, lower exercise tolerance.

PMID- 11234262
TI  - [Prognostic value of disturbed local contractility in stress-echocardiography
      performed in patients with non-Q myocardial infarction].
AB  - Prognostic value of viable dysfunctioning myocardium after non-Q infarction
      diagnosed at stress-echocardiography with low doses of dobutamine was clarified
      as a result of a one-year prospective study of 36 patients. Viable myocardium was
      found in 38.9% of the cases of non-Q myocardial infarction. Any stress-induced
      dynamics of local contractility correlates with high risk of repeat acute
      coronary events within the year after non-Q myocardial infarction.

PMID- 11234263
TI  - [Use of antioxidants and trimetazidine in preparation of patients with ischemic
      heart disease for coronary angiography].
AB  - Lipid peroxidation, cell stability, lipid spectrum, conjunctival
      microcirculation, levels of ceruloplasmin and myoglobin were studied in 107 males
      with ischemic heart disease before and after coronaroangiography by M. Judkins
      (CAG). It was found that CAG provokes oxidative stress, promotes
      membranodestructive processes, dyslipidemia and circulation disorders in the
      bulbar conjunctive. Preventive (3 days before CAG) administration of alpha
      tocopherol or emoxipin proved cardioprotective. The highest cytoprotective effect
      was produced by trimetasidine given 10 days before the procedure.

PMID- 11234264
TI  - [Transesophageal echocardiography in ischemic stroke: the detection of disorders
      and the indication for the procedure].
AB  - The authors present the results of transthoracic and transesophageal
      echocardiographic examination (TEE) of 53 survivors of ischemic stroke (IS). The
      following indications for TEE in IS patients were determined: the presence of
      permanent or paroxysmal arrhythmia of different etiology for verification of
      intracavitary thrombosis and its risk factors; identification and assessment of
      embologenic risk of cardial changes detectable at TEE genesis of which is not
      still clear; the presence of cryptogenic stroke.

PMID- 11234265
TI  - [The comparison of the efficacy of atenolol and isosorbide dinitrate therapy in
      chronic hypotension patients with stable angina pectoris].
AB  - Antianginal efficacy of atenolol (A) and isosorbide dinitrate (ID) was compared
      in a long-term randomized, single-blind, crossover, placebo controlled trial in
      71 patients with combined stable angina pectoris and chronic hypotension (Hpts)
      and in 38 normotensive patients with angina of effort (Npts). Paired bicycle
      tests showed anti-ischemic activity of drugs: A in 75% and ID in 49% of Hpts, A
      in 83% and ID in 82% of Npts. Antianginal effect of 25 mg A was observed in 49%
      of Hpts (vs 6% of Npts; p < 0.01). Secondary resistance to A effect was developed
      on the treatment week 2-4 in 13% of Hpts (vs 0 in Npts) tolerance to ID effect-
      on week 1-2 in 71% of Hpts (vs 15% of Npts; p < 0.01) as evidenced by T1-199
      exercise myocardial scintigraphy. Hpts needed individual ID therapy with a long
      term ID-free period during 8-16 days (vs 3-5 in Npts; p < 0.05) to avoid
      tolerance. Stable antianginal ID effect manifested with a decrease of myocardial
      perfusion defect size by 43.1 +/- 1.3% (p < 0.05).

PMID- 11234266
TI  - [Efficiency of low-intensity laser radiation in essential hypertension].
AB  - In a placebo-controlled study an antihypertensive activity of low-intensive laser
      radiation (LILR) was evaluated in 52 males with essential hypertension stage I.
      The placebo group consisted of 14 matched patients. LILR was used as monotherapy
      of 10 daily procedures. This treatment significantly lowered systolic, diastolic
      and mean arterial pressure. Moreover, diastolic arterial pressure did not rise
      high at submaximal bicycle exercise. Total peripheral vascular resistance also
      decreased. A good hypotensive effect was achieved in 90.4% cases. Thus, LILR is a
      highly effective treatment in essential hypertension stage I.

PMID- 11234267
TI  - [Diagnosis of myocardial lesions in infectious endocarditis].
AB  - To decide on treatment policy and specify prognosis in infectious endocarditis
      (IE) it is necessary to investigate myocardium. This is better to do using most
      informative criteria of myocardial affection--structural and geometrical changes
      of the left ventricle, various focal lesions, high-grade ventricular
      extrasystole, supraventricular tachycardia, atrioventricular block of various
      degree.

PMID- 11234268
TI  - [Quality of life in anxiety disorders in patients with rheumatoid arthritis].
AB  - Quality of life (QL) in patients with rheumatoid arthritis (RA) and anxious
      disorders was estimated according the scale of S. Roberts and M. Eliot. Anxious
      disorders were evaluated by RA patients' personality profile described by MMPI,
      Beck's questionnaire, Spilberger's test. In RA running for more than 5 years, QL
      tends to decrease, though subjectively the patients overestimate their QL. This
      leads to the loss of a direct correlation with psychological personality traits.
      The conventional treatment raises QL and restore the lost correlations. The
      persisting high level of anxiety and lowering of emotional functioning require
      administration of psychotropic drugs to improve adaptation of RA patients.

PMID- 11234269
TI  - [The role of beta-blockers in the treatment of chronic cardiac failure].

PMID- 11234270
TI  - [Cholecystectomy by mini-approach in the treatment of cholelithiasis].
AB  - Along with wide-spread laparoscopic cholecystectomy, cholelithiasis can be
      treated with another sparing technique--miniaccess cholecystectomy (MACE). Case
      histories and long-term treatment outcomes were analysed for 168 patients aged 23
      77 years subjected to MACE with elements of open laparoscopy for chronic
      calculous cholecystitis. Surgery was made using a special surgical kit "Mini
      assistant" by the team of two surgeons and an instrument nurse. After MACE the
      patients resume their jobs after a shorter period of inability, suffer from side
      effects of surgery in rare cases, have higher quality of life than patients after
      laparoscopic cholecystectomy.

PMID- 11234272
TI  - [Dilren efficacy in postmyocardial infarction patients].
AB  - 25 survivors of primary macrofocal myocardial infarction (MI) were treated for a
      year with children. The response in 9(36%) patients was achieved with a single
      dose 180 mg, in 16(64%) patients with concomitant arterial hypertension the dose
      was raised to 300 mg. No fatal outcomes were registered. Repeated IM developed in
      4(16%) patients. 15(60%) patients improved, deterioration was seen in 4(16%)
      patients. Dilren-induced complications occurred in 3(12%) patients.

PMID- 11234271
TI  - [Gastric, duodenal ulcer, Helicobacter pylori and secretory immunoglobulin A
      before and after the surgery].
AB  - The analysis of Helicobacter pylori (HP) and secretory IgA (SIgA) effects on the
      course and recurrence of gastroduodenal ulcer provides grounds to suggest that a
      pathogenic role of HP in secretory hypofunction of the gastric stump, unchanged
      mucosa and normal SIgA production is not leading. Elimination of the pathological
      process may bring functional restoration of the stump mucosa which adapts to HP
      invasion. Therefore, expansion of indications to eradication therapy in late
      postoperative period needs further study.

PMID- 11234273
TI  - [Side effects of non-steroid anti-inflammatory drugs in rheumatic patients].

PMID- 11234274
TI  - [A case of reactive histiocytosis in chronic viral hepatitis].

PMID- 11234275
TI  - [The review of the 50th annual conference of the American Hepatic Association
      (November 5-9, 1999, Dallas].

PMID- 11234276
TI  - [The development of the idea about the stages of clinical education (1842-1845).
      Communication 2. Introduction of a new curriculum for the Moscow University
      Department of Medicine].

PMID- 11234277
TI  - [Cryoglobulinemia associated with HCV infection].

PMID- 11234278
TI  - [Bacterial L-asparaginase and glutamin(asparagin)ase: some properties, structure
      and anti-tumor activity].
AB  - Experimental material on structurally and functional organization, regulation of
      biosynthesis and activity, mechanism of action, genetic determinants,
      heterologous expression of bacterial L-asparaginases is accumulated. The modern
      approaches to isolation and purification of these enzymes, some questions of
      practical using in oncology in the schedules combined chemotherapy of leukemia
      the native and modified forms of L-asparaginases are discussed. The some results
      before carried out in the IBMC RAMS and number institutes of the Russia on study
      bacterial L-asparaginases and glutamine(asparagine)ases are summarized.

PMID- 11234279
TI  - [Myelin basic protein. Structure, properties, function and role in diagnosing
      demyelinating diseases].
AB  - Physico-chemical properties and biological role of myelin basic protein (MBP)-
      one of the main myelin membrane proteins are reviewed. The data on MBP
      phosphorylation, methylation, fatty acid acylation and on interaction with lipid
      molecules in the human and animals bodies are presented. Much attention has been
      paid to the discussion of the diagnostic and clinical significance of the MBP, as
      the marker of demyelinating process in the central and peripheral nervous system.

PMID- 11234280
TI  - [Status of the blood and lung antioxidant system of the rat in toxic pulmonary
      edema].
AB  - The state of enzymatic and non-enzymatic components of antioxidant system and
      also lipid peroxidation processes in blood and lungs of rats with toxic pulmonary
      edema induced by inhalation of nitric oxides were investigated. The changes in
      the state of blood and lung antioxidant system components accompany the
      development of toxic pulmonary edema and coincide in time-course of edema
      manifestation. The determined changes were more pronounced in blood than in
      lungs.

PMID- 11234281
TI  - [Sex differences in the level of lipid peroxidation in white rats in a normal
      state and change in it after gonadectomy and administration of alpha-tocopherol].
AB  - The patterns of plasma lipid peroxidation (LPO) in normal male and female rats,
      after gonadectomy and alpha-tocopherol treatment were investigated. Sexual LPO
      differences were established and confirmed by the dispersion analysis. It is
      suggested that alpha-tocopherol participates in the regulation of steroid profile
      by regulating and adrenokynetic of the hypophysis.

PMID- 11234282
TI  - [Water-exchange processes in hyaline cartilage and its basic components in a
      normal state and in osteoarthritis].
AB  - The content of different forms of tissue water was studied in the normal
      articular cartilage and osteoarthrosis cartilage and its structural components:
      collagen, potassium hyaluronate, sodium chondroitinsulphate and its complexes. In
      the components of cartilage matrix a few of fractions of bound water different in
      the strength of binding are present. At the maximal humidity, all water in
      collagen binds with the active groups of biopolymers and in the
      glycosaminoglycans, in addition to bound water, are present, two crystal forms of
      freezing water (free water) at least. The quantity of free water in the collagen
      chondroitin sulphat membrane, is increased with the increase of chondroitin
      sulphate. In the collagen-hyaluronate complex, fraction of free water is found
      only at the low concentration of hyaluronate kalium. It was shown that in the
      hyalin cartilage, in different from the other connective tissue (skin, achilles
      tendon), the most part of water is free water and its quantity is increased in
      the osteoarthrosis. It is supposed that the rearrangement of binding and free
      water fractions in the osteoarthrosis is the result of deficiency of hyaluronic
      acid and therefore this may be regarded in the improvement of methods of
      treatment. This scientific and methodical approach allow to receive information
      on the forms and binding energy of water in the biological tissues, which is
      absorbed from fluids and steam phase and determine characters of the pathological
      changes.

PMID- 11234283
TI  - [The pathogenetic significance of disruption of antioxidant homeostasis status in
      patients with hypertension].
AB  - Antioxidative homeostasis was investigated in blood plasma and lymphocytes of
      patients with hypertonic disease (stage II). The intensification of lipid
      peroxidation was accompanied by accumulation of polyenic fatty acid derivatives
      and toxic dialdehydes and also by mobilization of lipid soluble vitamins. Vitamin
      E is probably involved into direct binding of toxic LPO products. Such changes
      provide high antioxidant activity and normal functioning of lymphocytes.

PMID- 11234284
TI  - [Lipid peroxidation and its connection with the change in composition and
      antioxidant properties of lipids in comatogenic forms of acute viral hepatitis
      B].
AB  - 81 patients of acute viral hepatitis B (AVHB) without symptoms of acute hepatic
      encephalopathy, 39 AVHB patients with such symptoms and 115 age and sex match
      healthy controls were biochemically and clinically investigated. Besides usual
      biochemical analyses, some special parameters such as interrelationship between
      the patterns of lipid peroxidation (LPO) (conjugated dienes and ketodienes and
      the lipid antioxidant activity) and alterations in lipid composition (content of
      total lipids, phospholipids and cholesterol) were studied in blood serum.
      Concentration of LPO products in patients with mild, moderate and severe AVHB
      without symptoms of encephalopathy was found to be significantly lower than in
      controls. Relative content of phospholipids in the total lipid fraction as well
      as antioxidant activity of lipids were elevated, while relative content of
      cholesterol and level of lipid oxidation were lowered. Increasing of antioxidant
      activity and decreasing of LPO products coincides with the severity of disease.
      Intensification of LPO occurs only in patients with symptoms of acute hepatic
      encephalopathy (in coma and precoma). High levels of LPO products and low levels
      of total phospholipids in blood serum were found in these patients. The
      persistence of a high level of peroxides in AVHB suggests the existence of
      severe, irreversible lesions. Among the patients a risk for the development of
      severe outcome was found. We suppose that the parameters of oxidative stress may
      be useful as early prognostic factor and that antioxidants may be a useful for
      the optimal therapy of comatogenous state of AVHB.

PMID- 11234285
TI  - [Features of disruption of certain components of carbohydrate metabolism in a
      combination of pulmonary tuberculosis and diabetes mellitus in people with
      haptoglobin phenotypes].
AB  - Sugar level in blood, the activity of lactate dehydrogenase (LDH), glucose-6
      phosphate dehydrogenase (G-6-PDH), 2,3-BPG content, HbA1C and the phenotype of
      haptoglobin were studied in 180 patients with lung tuberculosis and diabetes
      mellitus. The increased (2-4.2-fold) blood sugar level was found in 77.2%
      patients. It was accompanied by decreased activity of LDH (by 1.3-1.7 times), G-6
      PDH (by 15-45% in 87% patients). In patients with various haptoglobin phenotypes
      the content of HbA1C and 2.3-BPG was increased by 1.5-1.7 and 2-3 times,
      respectively. Clear differences in the studied parameters were found in patients
      with various phenotypes of haptoglobin (Hp). The most serious impairments of the
      studied parameters of carbohydrate metabolism were found in untreated patients
      with homozygote Hp phenotypes 2-2 and 1-1. Alterations found in the present study
      can be used for evaluating the depth of impairments of the carbohydrate
      metabolism in patients with combination of lung tuberculosis and diabetes
      mellitus.

PMID- 11234286
TI  - [Computer modeling of the three-dimensional structure of full-length cytochrome
      B5].
AB  - The computer-aided reconstruction of 3D structure of full-length cytochrome b5
      was done. Software Sybyl 6.4 from Tripos running on workstation Silicon Graphics
      Indigo2 (R4400, XZ) was used. The reconstruction was carried out by computer
      modelling of membrane part of cytochrom b5 with subsequent linking with known
      structure of water-soluble b5 part (fragment 5-91 of amino acid residues-file
      3B5C in the protein data bank, PDB). The obtained structure of full-length
      cytochrome b5 was refined in the mixture of polar and nonpolar solvents by
      molecular dynamics simulation and deterministic minimization. Molecular dynamics
      simulation was performed in periodic box of binary system of solvents with a step
      of 1 fs during 550 ps at constant number of particles, pressure and temperature.
      The balance of system was achieved after 400 ps. With period in 5 ps the
      potential energy was minimized without molecular dynamics interruption. As a
      result 100 conformations of full-length cytochrome b5 were obtained. Distribution
      of potential energy was from -2.7 x 10(4) to -4.2 x 10(4) kcal/mol. Conformation
      of cytochrome b5 with minimal value of potential energy was accepted as the
      final. Analysis of lipophilic surface of obtained model have shown that membrane
      bounded part is more hydrophobic and forms a loop structure. This model
      corresponds to some known experimental data about cytochrome b5 structure.

PMID- 11234287
TI  - [Methodical aspects of using furylacryloylphenylalanylglycineglycine for
      photometric determination of the activity of angiotensin-converting enzyme].
AB  - Different aspects of photometric assay of angiotensin converting enzyme (ACE)
      with synthetic cromogenic substrate N-(3-[2-furyl]-acryloyl)-phe-gly-gly (FAPGG)
      were evaluated. At FAPGG concentration exceeding 0.025 mM the absorbance does not
      follow Burger-Lambert-Bar dependences. Under three conditions the rate of
      absorbance of the reaction medium strongly depends on properties of spectral
      weight band. This explains dramatic interamlyser variations and complicetes
      standardization of the method. Linear dependence between photometic response and
      ACE activity. The employment of special inhibitor be recommended for elimination
      of interference.

PMID- 11234289
TI  - [Long flights and the risk of venous thrombosis].
AB  - It is pathophysiologically conceivable that prolonged air travel may lead to
      blood flow stasis and hypercoagulability of the blood. The available
      observational and case-control studies do not, however, indicate an increased
      incidence of venous thromboembolism amongst air travellers. In these studies bias
      may have been caused by patients visiting their own GP instead of the airport
      medical services, the omission of an objective test to establish the thrombosis,
      the selection of control patients with a different travel behaviour or the
      inclusion of flying times that were too short. If in the future it becomes
      apparent that patients with an increased likelihood of thrombosis risk developing
      venous thromboembolism as a result of prolonged air travel then preventive
      measures may be required. These could include short-term thrombosis prophylaxis
      or the wearing of special elastic stockings. Furthermore, all air travellers
      should be advised to keep moving during long flights and to drink plenty,
      preferably non-alcoholic beverages.

PMID- 11234288
TI  - [Illness after travel not always due to exotic disease].
AB  - It is extremely important to look for tropical and other exotic diseases in
      travellers who return with illness or become ill after travelling. Especially
      tropical diseases and exotic infectious diseases have to be excluded because of
      their possible fatal outcome. On the other hand, many travellers return with
      'common' not-exotic illnesses not related to their journey. When in such cases
      attention is only given to exotic causes of their illness, diagnosis can be
      delayed which may be harmful. This was the case in 5 patients: a woman aged 44
      years who suffered for months from bloody diarrhoea since her return from Brasil,
      due to a rectal adenocarcinoma, a 61-year-old man with diarrhoea upon returning
      from Egypt, who had hairy-cell leukaemia, a 17-year-old boy who developed a
      ketoacidotic diabetic crisis whilst on a journey in Uganda, but in whose case the
      first thoughts went to malaria, a 50-year-old man who suffered from throat pain
      since a journey through East Africa, during which he contracted a flu-like
      disease, and in whom Kahler's disease was diagnosed, and 69-year-old man
      suffering from recurrent fever and cough, in whom a radiological lesion was
      observed in the thorax which proved to be part of Wegener's disease.

PMID- 11234291
TI  - [Clinical thinking and decision making in practice. The internist as a consultant
      for a patient with unexplained anemia in the cardiology department].
AB  - A man aged 73, admitted because of unstable angina pectoris also had a anaemia
      with a haemoglobin concentration of 2.8 mmol/l. The department of Consultative
      Internal Medicine was asked to elucidate this anaemia. The anamnesis proved to
      contain extensive diagnostic tests concerning the anaemia which had had no
      results. In spite of a negative anamnesis, the low serum iron level had prompted
      an unsuccessful search for a source of haemorrhage in the proximal and distal
      parts of the digestive tract. The bone marrow had been examined three times
      without a clear diagnosis. It was also found that there had been a deviation from
      the classification of anaemia which should be guided by the size of the
      erythrocyte and the reticulocyte count. This had resulted in diagnostics that
      where inconvenient to the patient; also the patient had been treated without
      success with ferrofumarate. Ultimately, he proved to suffer from autoimmune
      hypothyroidism; the anaemia was resolved by substitution therapy.

PMID- 11234290
TI  - [Supraventricular tachycardia and premature atrial contractions in fetus].
AB  - Foetal arrhythmias are encountered in 1-2% of pregnancies and 10% of these are
      associated with some form of foetal mortality or morbidity, including structural
      heart disease, foetal death and neurological complications. The most frequent
      types of arrhythmia are supraventricular arrhythmias of which the innocent
      premature atrial depolarisations make up 85%; 10% are tachycardias with a foetal
      heart rate of over 180/min. Echocardiographic evaluation is required to exclude
      associated structural abnormalities and to decide whether therapy is required.
      The prognosis of a foetus with tachycardia depends on the presence of associated
      pathology, the type of arrhythmia, the presence of foetal hydrops, the heart rate
      and the adequacy of treatment. The treatment of foetal tachycardia depends on the
      type of the tachycardia and since most tachycardias are of supraventricular
      origin the therapeutic armamentarium includes digoxin, sotalol and flecainide,
      each with its specific side effects. Foetal tachycardia patients require
      immediate diagnosis and if necessary therapy in a specialized center.

PMID- 11234292
TI  - [Progress in the field of medical devices for diabetes].
AB  - In the eighties major improvements were made in insulin injection and home blood
      glucose monitoring. However, in the nineties further improvements were rather
      disappointing. Despite considerable effort, non-invasive, continuous monitoring
      glucose sensors are still not ready for marketing. It will take 10-20 years
      before 'closed-loop systems' will appear, with the amount of insulin released by
      the pump adjusted automatically on the basis of the measuring results of a
      permanently implanted blood glucose sensor. Islet cell transplantation, if
      possible in a way that abolishes the need to take immunosuppressive medicines, is
      still under development. The number of people suffering from diabetes in the
      Netherlands is estimated to increase from about 285,400 in 1999 to about 400,000
      in 2020. The costs of medical devices for diabetes will probably double in 2020.
      However, increased costs for devices may improve the quality of life and may
      result in decreased expenditure in other parts of health care by reducing the
      long-term complications.

PMID- 11234293
TI  - [Diagnostic image (25). Carpal arthrosis].
AB  - A 79-year-old man had a tumor at the left wrist, caused by posttraumatic
      arthrosis of the carpalia.

PMID- 11234294
TI  - [Maintenance dose requirement for phenytoin is lowered in genetically impaired
      drug metabolism independent of concommitant use of other antiepileptics].
AB  - OBJECTIVE: To investigate the effect of genetically determined impaired drug
      metabolism and of the use of comedication on phenytoin maintenance dose
      requirement. DESIGN: Descriptive. METHOD: In 60 patients on long-term phenytoin
      therapy the concentration of phenytoin in serum was measured and CYP2C9
      genotyping was performed (mutant alleles of CYP2C9 are associated with impaired
      phenytoin metabolism). In addition, the use of other antiepileptics concurrently
      with phenytoin was reviewed: phenobarbital, carbamazepine and valproic acid.
      CYP2C9 genotype and comedication were connected to phenytoin daily dose
      requirement. The 60 patients were 38 men and 22 women, between 16 and 74 years of
      age, and all mentally disabled. RESULTS: Genotyping revealed that of the 60
      patients 38% (n = 23) carried at least one mutant CYP2C9 allele. Their mean dose
      of phenytoin was 199 mg dd, while the mean required maintenance dose in non
      carriers (n = 37) was 287 mg dd (p < 0.01). When the use of comedication was
      taken into account, it appeared that the mean phenytoin daily doses in the
      different comedication groups did not differ significantly. CONCLUSION: Patients
      with a genetically determined impaired phenytoin metabolism required on average a
      30% lower dose than those with a normal metabolism, while the concomitant use of
      other antiepileptics appeared to have no effect on phenytoin dose requirement.

PMID- 11234295
TI  - [An adolescent with hemolytic anemia and coagulation disorders as manifestation
      of Wilson's disease, treated with liver transplantation].
AB  - A 16-year-old woman presented with anaemia, jaundice, vomiting and nosebleed. She
      had acute hepatic failure and haemolytic anaemia and developed acute respiratory
      distress syndrome (ARDS). Wilson's disease was diagnosed. After the ARDS resolved
      the patient underwent a successful orthotopic liver transplantation. Diagnostic
      combinations for Wilson's disease are ceruloplasmin < 0.2 g/l with Kayser
      Fleischer rings, liver copper > 250 micrograms/g (dry weight) with Kayser
      Fleischer rings, or homozygosity for a Wilson mutation on the 13th chromosome. In
      acute liver failure a copper excretion in 24 h-urine above 1 mg is diagnostic for
      Wilson's disease, while an elevated serum copper concentration makes this
      diagnosis very likely. Therapeutic options for Wilson's disease are chelation
      therapy and liver transplantation; in most cases of acute liver failure due to
      Wilson's disease orthotopic liver transplantation (preceded by albumin dialysis)
      is indicated. Nazer's index should be used in addition to the regular King's
      College criteria for liver transplantation indication.

PMID- 11234297
TI  - [Iron deficiency in premenopausal women and criteria for iron supplementation].

PMID- 11234296
TI  - [Migrating swellings from Asia: gnathostomiasis].
AB  - Two patients suffered from intermittent subcutaneous swellings of the face. A 41
      year-old man recalled a recent episode with severe thoracic pain and at that time
      pleurisy was documented. In this patient there was pronounced eosinophilia. The
      other was a 32-year-old woman. Both patients had traveled to southeast Asia.
      Antibodies against Gnathostoma spinigerum were detectable in both patients. The
      first patient was treated with albendazole 200 b.i.d. for three weeks, but
      because of recurrent facial swelling, he was treated again with albendazole at a
      higher dose: 400 b.i.d. for eight weeks, which the swellings did not recur. The
      second patient was not treated because the frequency of the swellings had already
      decreased spontaneously. Gnathostomiasis is an infection by the nematode G.
      spinigerum. The main route of human infection is by eating insufficiently not
      well-cooked fish or frog. The initial infection is often not recognised, but
      severe symptoms can occur. In humans, the larva of the nematode does not develop
      further but may wander through the subcutaneous tissues. Untreated, the infection
      usually runs a mild, self limiting course, but complications such as invasion of
      the central nervous system or of the eye have been described. Treatment with
      albendazole reduces recurrence of swellings.

PMID- 11234298
TI  - [Diagnostic image(3) Fetal resorption].

PMID- 11234299
TI  - [The anatomical pathologist and the diagnosis of genetic risk].

PMID- 11234300
TI  - [Surfactant protein and thyroid transcription factor 1 in pleuro-pulmonary
      neoplasia. Immunohistochemical study].
AB  - Aim of this work was to investigate the ability of the antibodies against
      Surfactant proteins (SP) and Thyroid transcription factor 1 (TTF-1) to
      distinguish primary neoplasms of the lung from metastatic carcinomas to the lung
      and pleural mesotheliomas. We evaluated the immunohistochemical expression of the
      antibodies anti SP-A, SP-B, pro SP-C, SP-D, and TTF-1 in a series of 56 primary
      lung carcinomas, 9 metastatic carcinomas to the lung, 5 pleural mesotheliomas and
      8 non-pulmonary carcinomas. Among primary lung neoplasms, only adenocarcinomas
      immunostained for all SP (specificity = 1; total sensitivity = 0.52). TTF-1 had
      an excellent specificity (= 1), but a weak sensitivity (= 0.34) in recognizing
      primary lung carcinomas. TTF-1 was present in lung adenocarcinomas which were
      negative for SPs; however it failed to distinguish the subtypes. Pleural
      mesotheliomas, pulmonary metastases and non-pulmonary carcinomas were not
      immunoreactive for SP-A, SP-B, SP-D, and TTF-1. Pro SP-C was positive also in the
      adenocarcinomas of the large bowel and in their pulmonary and nodal metastases.
      These results demonstrate that the combined use of antibodies anti SP-A, SP-B and
      TTF-1 is the best association in distinguishing primary lung carcinomas from
      metastatic carcinomas to the lung and pleural mesotheliomas.

PMID- 11234301
TI  - [Primary gastric lymphomas. Clinico-pathological study and evaluation of
      prognostic factors in 65 cases treated surgically].
AB  - Based on the histological criteria proposed by the REAL and adopted by the WHO
      Classification, 30 cases of MALT type lymphoma, 18 cases of diffuse large B cell
      lymphoma (DLCL), and 17 cases of DLCLs, associated with a MALT type, were
      identified in a series of 65 surgically treated primary gastric lymphomas. The
      clinical records of the patients were analyzed retrospectively and the resected
      specimens were immunostained for bcl-2, p53 and Ki-67. Primary gastric DLBCLs,
      with or without a MALT type component, disclosed a higher stage of local
      extension, a more frequent nodal involvement and a significantly worse survival
      than pure MALT types. High p53 expression and high proliferation rate correlated
      with the presence of a large cell component and appeared useful for its
      identification in mixed forms. Low bcl-2 expression discriminated DLCL from
      DLCL/MALT. Tumor size, stage and Mib-1 index revealed a value in predicting
      prognosis.

PMID- 11234303
TI  - [Simultaneous detection and typing of human papillomavirus in cervical biopsies
      using PCR-reverse hybridization].
AB  - INTRODUCTION: Genotyping of Human papillomavirus (HPV) is an important step in
      the clinical evaluation of the oncogenic risk associated with HPV infection of
      cervical mucosa. The purpose of this work was to develop a fast PCR-reverse
      hybridization assay (PCR-RH) for the simultaneous detection and genotyping of
      anogenital HPVs. METHODS: HPV DNA from cervical biopsies was amplified by
      consensus primer-PCR. Digoxigenin-labeled PCR products were hybridized to type
      specific probes anchored to the surface of plastic microwells and revealed by an
      ELISA system. RESULTS: The method was tested on 115 clinical samples (81
      koilocytic atypias, 11 CIN1, 10 CIN2, 12 CIN3 and 1 squamous carcinoma). HPV DNA
      was found in 56.7% koilocytic atypias, in 90.9% of CIN1 and in 100% of CIN2 and
      higher-grade lesions. Thus, PCR-RH is sensitive, rapid, easy-to-perform and
      readily applicable to the routine analysis of a large number of samples.

PMID- 11234302
TI  - [The role of human papillomavirus in cyto-histological practice: distribution and
      prevalenceof hig-risk strains (16, 18, 31, 33, and 35) in intraepithelial lesions
      and neoplasia of the uterine cervix].
AB  - INTRODUCTION: Many studies have already shown the association of persistent
      infection of human high risk papillomavirus (HPV) with the development of pre
      invasive and invasive cervical disease. MATERIALS AND METHODS: We evaluated the
      use of high risk HPV testing in a study of about 1908 women, aged 29-78, who
      attending, from 1996 to 1998, the Sant'Anna Hospital in Turin for routine, second
      level smears and histopathological diagnosis. We considered all cervical lesions:
      ASCUS, LSIL, HSIL, squamous and adeno invasive cancers. HPV testing was performed
      by polymerase chain reaction (PCR) using L1 consensus primers which can detect
      almost all infections (high and low risk types). The most important high risk HPV
      types (16, 18, 31, 33 and 35) were tested using specific primers. RESULTS: The
      prevalence of high risk HPV was: ASCUS 42.2%, LSIL 39%, HSIL 73.5%, squamous
      invasive cancers 98.3% and adeno 100%. In addition HPV 16 is the most represented
      type in all lesions: ASCUS 40%, LSIL 62%, HSIL 71.2% squamous invasive cancers
      73.3% and adeno 50.6%. In addition we study the mean age of cervical cancer onset
      compared with the different high risk HPV types. We found that HPV 18 related
      cancer occurs in younger women (mean age 41 years; range 39-42). CONCLUSIONS: The
      addition of high risk HPV testing to cytology may improve early identification of
      women at risk for cervical cancer.

PMID- 11234304
TI  - [Localized lymph node lymphangiomyoma. Description of 2 cases].
AB  - Lymphangioleiomyomatosis is a rare disease characterized by an immature-appearing
      smooth muscle proliferation in the lung and along axial lymphatics. Rarely it is
      limited to lymph nodes, without extranodal disease. Two cases of localized nodal
      lymphangiomyoma in a 48 and 54 year-old women are presented: in both cases the
      lesion was limited to pelvic lymph nodes and it was an incidental finding during
      staging for tumours of the gynaecological tract.

PMID- 11234305
TI  - [Primary tumors of the central nervous system: histogenetic classification, grade
      of malignity, clinico-pathologic features, and therapeutic criteria].
AB  - We review the current classification of the central nervous system neoplasms
      focusing on grading and new clinicopathological entities. Moreover a brief
      synopsis on up to date treatments in different groups of neoplasms is given.

PMID- 11234306
TI  - [Diagnosis of (neuro)endocrine tumors: a brief practical review of new
      classifications and new markers].

PMID- 11234307
TI  - [AD 1700: De morbis artificum diatriba Bernardini Ramazzini in Patavino Archi
      lyceo practicae medicinae ordinariae publici professoris. Occupational medicine
      and epidemiology are born].

PMID- 11234308
TI  - [Gorse: a noxious plant and even a bit vulgar. But....].

PMID- 11234309
TI  - [The placenta].

PMID- 11234310
TI  - Bariatric surgery in the 1990's.

PMID- 11234311
TI  - [Coronary artery bypass by mini-thoracotomy: noticeable benefits with clinical
      experience of the treatment team].
AB  - AIM OF THE STUDY: Minimally invasive coronary artery bypass surgery is
      fundamentally different as compared to open sternal approach under
      cardiopulmonary bypass. Modifications of the surgical, anesthesiologic and post
      operative techniques are necessary before evaluation of its real benefit. We
      analyze the potential effect of a learning period on the short term results of
      this technique. METHODS: From July 1997 to February 1999, 20 patients were
      operated using this method. We compare the results of the first 10 patients
      (group 1: 8M/2F, 59.6 +/- 13.8 years) to those of the last 10 patients (group 2:
      8M/2F; age = 63.2 +/- 6.1 years). DISCUSSION: Progress between the two groups is
      striking. Left anterior descending coronary clamping time could be reduced from
      28.5 +/- 2.4 min. in group 1 to 22.2 +/- 1.8 min. in group 2 (p < 0.05), and
      operative time was reduced from 125 +/- 4 min. to 97 +/- 5 min. (p < 0.005). The
      post-operative atrial fibrillation rate diminished from 4/10 in group 1 to 1/10
      in group 2.3/10 patients in group 1 suffered a post-operative pneumonia whereas
      none in group 2 had pulmonary complication. The stay in the intensive care unit
      could be reduced from 2.3 +/- 0.3 days to 1.4 +/- 0.2 days (p < 0.05) and the
      total post-operative stay diminished from 8.5 +/- 0.9 days to 4.7 +/- 0.5 days (p
      < 0.005). CONCLUSION: There are evidence for a learning period in minimally
      invasive cardiac surgery. Short term benefits of this technique are then evident
      as demonstrated by a reduction in the ICU stay and the hospital stay.

PMID- 11234312
TI  - Short- and long-term results of total vs subtotal thyroidectomies in the surgical
      treatment of Graves' disease.
AB  - OBJECTIVE: Approximately one out of five patients with Graves' disease (GD)
      undergoes a thyroidectomy after a mean period of 18 months of medical treatment.
      This retrospective and non-randomized study from a teaching hospital compares
      short- and long-term results of total (TT) and subtotal thyroidectomies (ST) for
      this disease. METHODS: From 1987 to 1997, 94 patients were operated for GD.
      Thirty-three patients underwent a TT (mostly since 1993) and 61 a ST (keeping 4
      to 8 grams of thyroid tissue--mean 6 g). All patients had received
      propylthiouracil and/or neo-mercazole and were in a euthyroid state at the time
      of surgery; they also took potassium iodide (lugol) for ten days before surgery.
      RESULTS: There were no deaths. Transient hypocalcemia (< 3 months) occurred in 32
      patients (15 TT and 17 ST) and persistent hypocalcemia in 8 having had TT. Two
      patients developed transient recurrent laryngeal nerve palsy after ST (< 3
      months). After a median follow-up period of seven years (1-15) with five patients
      lost to follow-up, 41 patients having had a ST are in a hypothyroid state (73%),
      thirteen are euthyroid (23%), and two suffered recurrent hyperthyroidism,
      requiring completion of thyroidectomy. All 33 patients having had TT--with follow
      ups averaging two years (0.5-8)--are receiving thyroxin substitution.
      CONCLUSIONS: There were no instances of persistent recurrent laryngeal nerve
      palsy in either group, but persistent hypoparathyroidism occurred more frequently
      after TT. Long after ST, hypothyroidism developed in nearly three of four cases,
      whereas euthyroidy was maintained in only one-fourth; recurrent hyperthyroidy was
      rare.

PMID- 11234313
TI  - Streptococcal toxic shock syndrome revealed by a peritonitis. Case report and
      review of the literature.
AB  - Group A streptococcus (GAS) or Streptococcus pyogenes cause a variety of life
      threatening infectious complications including necrotizing fasciitis, purpura
      fulminans and streptococcal toxic shock syndrome (STSS). Exotoxins that act as
      superantigens are felt to be responsible for STSS. These exotoxins are highly
      destructive to skin, muscle and soft tissue. This syndrome has a rapid and
      fulminant course with frequently fatal outcome. GAS remains sensitive to
      penicillin but in serious infection a combination of clindamycin and ceftriaxone
      or meropenemum is recommended. Several studies have shown that mortality was
      dramatically reduced in STSS patients treated with immunoglobulin G given
      intravenously (IVIG). Early recognition of this most rapidly progressive
      infection and prompt operative debridement are required for successful
      management. This report presents a female patient at two month post-partum with a
      peritonitis and multi-organ failure.

PMID- 11234314
TI  - [Chronic cholecystitis simulating gallbladder tumor with liver abscess. Case
      report].
AB  - We report on a 58 year-old male who presented with nausea, a painful tumor
      palpable in the upper right epigastrium, moderate fever without leukocytosis.
      Both ultrasonic scan and subsequent computerized tomography lead to the primary
      diagnosis of a malignant tumor of the gall bladder infiltrating the liver and
      inducing an intrahepatic abscess formation in segments 4b and 3. The patient was
      scheduled for emergency operation, i.e. abscess drainage, cholezystectomy, and
      hemihepatectomy. However, at operation a purulent chronic cholezystitis was found
      without involvement of the liver itself. Consequently, a cholezystectomy was
      necessary and performed. Histological examination of the gall bladder revealed no
      signs of malignancy. The patient had an uneventful recovery and was discharged on
      post-operative day seven. This case report shows the difficulties in the
      differential diagnosis of inflammable processes and malignancies, which affect
      the gall bladder and adhering structures. A chronic inflammable process can mimic
      solid tumors. Despite cost-effective diagnostic tools the correct diagnosis was
      finally found by surgery.

PMID- 11234316
TI  - Appendicitis caused by caecal carcinoma--a case report.
AB  - Appendicitis can occur rarely in association with carcinoma of the caecum,
      particularly in elderly patients. The prognosis for caecal or proximal colonic
      neoplasm presenting as appendicitis is poor. This is in part due to the
      association being missed at the initial laparotomy. We report a case of acute
      appendicitis provoked by an adenocarcinoma of the caecum which obstructed the
      lumen of appendix in an 84 years old patient by which a simple ileocaecal
      resection was performed. The difficulties of identifying a small tumor at
      laparotomy and the implication for optimal treatment are emphasized. It is
      suggested that a more aggressive attitude should be taken in the pre and
      postoperative management of any patient over 50 years of age who presents with
      appendicitis.

PMID- 11234315
TI  - [Monstrous, retroperitoneal liposarcoma--a case report].
AB  - Liposarcomas comprise about 20% of soft tissue sarcomas and occur in 14% in the
      retroperitoneal space originating in one third from the perirenal fat. The case
      of a patient with an extraordinary huge, resectable, well-differentiated
      retroperitoneal liposarcoma is reported. The presenting symptoms were abdominal
      pain and distension as well as weight gain. Magneticresonance imaging revealed a
      huge retroperitoneal tumor suspected of well-differentiated liposarcoma. Curative
      resection of the tumor could be obtained. Only 50% of all tumors are excised
      without residual tumor and recurrence, occurring in 90% after 10 years, is the
      main therapeutic challenge. Since neoadjuvant and adjuvant therapy as well as
      intraoperative radiotherapy failed to prove prognostic value, curative resection
      remains the main treatment for primary and recurrent liposarcomas.

PMID- 11234317
TI  - [Contact litholysis of gallstones with methyl tert-butyl ether in risk patients-
      a case report].
AB  - INTRODUCTION: Before laparoscopic cholecystectomy and endoscopic therapy became
      gold standard the nonsurgical treatment of symptomatic cholelithiasis, i.e.
      contact dissolution using methyl-tert-butyl ether (MTBE), was a valuable
      alternative. Even nowadays, stone dissolution may be helpful in critically ill
      patients. CASE REPORT: A 85-year-old man admitted in poor general condition due
      to cholangitis with septicemia following endoscopic retrograde
      cholangiopancreatography (ERCP) with papillotomy and partial stone removement
      because of impending perforation of the gallbladder empyema was treated by a
      percutaneous cholecystostomy with a pigtail catheter. After clinical improvement
      a successful contact dissolution was initiated by irrigation of the common bile
      duct and gallbladder with MTBE. The patient is asymptomatic three months after
      treatment. DISCUSSION: Symptomatic cholelithiasis is usually treated by
      endoscopic techniques. Percutaneous cholecystostomy in association with contact
      litholysis using MTBE is an effective treatment in patients who can not be
      operated due to critical conditions. The success rate in case of cholesterol
      stones averages 70 to 95% depending on number and size of stones. It is a non
      invasive treatment with few side effects. CONCLUSION: In high-risk patients with
      severe cholecystitis, percutaneous catheter cholecystostomy combined with contact
      litholysis using MTBE is a successful, safe, and cheap treatment.

PMID- 11234318
TI  - [Surgical dogmas throughout history].
AB  - This article is a historical analysis of the role of dogmas and dogmatic thinking
      in surgery from the great pioneers and teachers of surgery of a hundred years ago
      to the present time. Medical knowledge applied schematically creates security and
      may benefit many patients, but when simplification and standardization
      degenerates into rigid dogma, creative thinking will be obstructed and the
      development of innovative concepts becomes difficult. In the old times of the
      19th and early years of the 20th century, dogmas usually originated from the
      teaching of great and prestigious pioneers of surgery. Nowadays, dogmatic
      thinking may come as practice guidelines, protocols of consensus conferences and
      even from the interpretation of the results of prospective randomized studies.
      The author illustrates these thoughts by a number of examples taken from the
      history of surgery over the last one hundred years: The controversy between
      Sauerbruch's (under)pressurized chamber and the concept of intratracheal positive
      pressure ventilation and its influence on the development of thoracic surgery
      during the first half of the 20th century, the role of serendipity and undogmatic
      thinking in the development of damage control surgery towards the end of the 20th
      century, the fascinating history of two operations which kept their position as
      gold standard for almost a century, i.e. Halsted's radical mastectomy for breast
      cancer and the Miles operation for cancer of the rectum.

PMID- 11234319
TI  - [Lymphangioma of the mesentery--surgical indication].
AB  - The discovery of a cystic image in the mesentery is a difficult diagnostic and
      therapeutic problem. We report the case of a 25-year-old female with a mesenteric
      lymphangioma, which was resected after careful consideration. The complications
      due to the expansion of this benign tumour are reviewed, and the surgical
      indications discussed.

PMID- 11234320
TI  - The malaria cauldron of Southeast Asia: conflicting strategies of contiguous
      nation states.
AB  - The past half-century or so has witnessed dramatic failures but also some
      successes in control of malaria in the world at large. South and Southeast Asia
      have had their share of both outcomes, a scenario that reflects many variables in
      control programs: technology, management strategy, human and financial resources.
      However, at least equally culpable have been major wars and minor conflicts,
      economic growth and stagnation, inequity of opportunity, urbanisation,
      deforestation, changing transport and communications. The history of malaria is
      thus an integral part of the broader political and economic evolution of the
      region, as well as the story of the wisdom and unwisdom of malaria specialists.
      In positive reflection on the latter, systematic organisational effort using
      standard tools of trade has seen the gradual elimination of major malaria foci
      from central plain regions of a number of nations in this large region, with
      residual foci at forested border areas. In many cases there is good evidence of
      sustainability of elimination in defined areas but the differing success stories
      reflect in part conflicting strategies in neighboring nation states. On the other
      hand, physical conflicts, population migration, inequitable economic change,
      border instability and many other socio-economic variables can be clearly seen to
      undermine the most ingenuous strategies. Undoubtedly the single most important
      negative ingredient is the rise and spread of multi-drug resistant falciparum
      malaria that has its epicenter in Southeast Asia, from which it threatens the
      world in insidious fashion. Containment of this phenomenon has been the focus of
      attention for 30 years, more particularly the past decade, and represents the
      greatest challenge at this time in predicting the continuing impact of malaria
      globally on human history. So too does the compelling necessity to link malaria
      control with macro and micro economic planning. This challenge impinges on the
      sovereignty of individual nations in this region, for they exist in contiguity,
      so that successful applications of technology require collaborative political
      determination.

PMID- 11234321
TI  - The disappearance of Dutch malaria and the Rockefeller Foundation.
AB  - Sixty years ago Professor Nico Swellengrebel wrote his famous book 'Malaria in
      the Netherlands' (Swellengrebel and de Buck, 1938). At that time tertian malaria
      was still endemic, with its epidemic ups and downs. Malaria disappeared as
      recently as 1960 and the Rockefeller Foundation (RF) contributed substantially to
      this effect. The Rockefeller Archives proved a valuable source of anecdotal
      information, which puts the scientific publications of the Dutch malariologists
      in a more vivid perspective. Following the course of history, first the already
      existing links with the RF are explained along with some peculiarities of tertian
      malaria in the Dutch temperate climate. The emergence of a new epidemic during
      the war years and the implication of new tools and principles for control as
      advocated by the RF are described. The subsequent shriveling of the vector
      population and the disappearance of malaria are presented, along with some
      details about the reluctance of WHO to declare the Netherlands malaria-free.
      Finally, recent unrest about possible return of malaria is put into perspective.

PMID- 11234323
TI  - Internationalism and nationalism: the Rockefeller Foundation, public health, and
      malaria in Italy, 1923-1951.
AB  - The Rockefeller Foundation's support of malaria control and public health in
      Italy over three decades, the 1920s, 1930s and 1940s, was one of the foundation's
      most successful collaborations in its history. Nearly one-sixth of the funds the
      Rockefeller Foundation allocated for malaria programs was spent in Italy in those
      years. Outstanding research, a new and important institution, and decided
      improvements in public health were historically-significant results. The three
      most important episodes of this American-Italian relationship were the operations
      of the Stazione Sperimentale per la Lotta Antimalarica, the founding of the
      Istituto Superiore di Sanita, and the campaign to eradicate mosquitoes in
      Sardinia. In each of these episodes there was a tension between the international
      aspects and national aspects of the partnership that to some degree limited its
      success.

PMID- 11234322
TI  - Malaria eradication: the Taiwan experience.
AB  - In November 1965, the World Health Organization (WHO) certified Taiwan as an area
      where malaria had been eradicated. Malaria eradication in Taiwan resulted from
      government initiatives and involvement, careful planning and organization, the
      development of basic health structure and community support, as well as the
      cooperation and assistance of international agencies. The Japanese colonial
      government of Taiwan had contributed to the antimalarial efforts through the
      establishment of a rudimentary health infrastructure and introduction of measures
      to combat malaria and other diseases during their occupation of the island from
      1895 to 1945. The Chinese government regained control of the island after Japan's
      surrender in 1945, and with the support of the Rockefeller Foundation,
      established a research institute to investigate the malaria problem. Political
      instability in 1949, however, caused the Foundation to end its support. After the
      Nationalist government moved to Taiwan, it continued antimalarial efforts which
      received the support of WHO and other international agencies. While Taiwan
      followed closely WHO's guidelines and plan of attack, the development of the
      program illustrates the importance of local factors in shaping its actual
      implementation and eventual success. Malaria eradication in Taiwan went through
      the following phases: preparatory (1946-1951); attack (1952-1957); consolidation
      (1958-1964); and maintenance (after 1965).

PMID- 11234324
TI  - Resurgence of malaria in Bombay (Mumbai) in the 1990s: a historical perspective.
AB  - Bombay has achieved extraordinary success in controlling its malaria problem for
      nearly six decades by relying primarily on legislative measures and non
      insecticidal methods of mosquito abatement. In 1992, however, malaria reemerged
      in Bombay with a vengeance. During 1992-1997, the city witnessed a manifold
      increase in the number of malaria cases diagnosed and treated by the public
      health system. The large number of malaria patients treated by private
      practitioners was not recorded by the municipal malaria surveillance system
      during this period. In 1995, at the peak of the resurgence, public health
      officials of the Municipal Corporation of Greater Bombay (MCGB) confirmed that
      170 persons in the city had died due to malaria. The crisis was unprecedented in
      Bombay's modern public health history. In response to intense criticism from the
      media, the city's public health officials attributed the resurgence to the global
      phenomenon of mosquito-vector resistance to insecticides, and Plasmodium
      resistance to antimalarial chemoprophylaxis and treatment. Local scientists who
      investigated the problem offered no support to this explanation. So what might
      explain the resurgence? What factors led the problem to reach an epidemic level
      in a matter of two or three years? In addressing the above principal questions,
      this paper adopts a historical perspective and argues that in the resurgence of
      malaria in Bombay in the 1990s, there is an element of the 'presence of the
      past'. In many ways the present public health crisis in Bombay resembles the
      health scenario that characterized the city at the turn of the 19th century. It
      is possible to draw parallels between the early public health history of malaria
      control in Bombay, which was punctuated by events that followed the bubonic
      plague epidemic of 1896, and the present-day malaria epidemic punctuated by the
      threat of a plague epidemic in 1994. As such, the paper covers a long period, of
      almost 100 years. This time-depth is used to illustrate how malaria control
      programs in Bombay and in other parts of India have evolved through a combination
      of local historical forces and political expediencies in the context of
      technological developments. The boom in construction activities in Bombay
      following the liberalization of the Indian economy in 1991, and the local
      politics affecting administrative practices of the MCGB, are discussed as crucial
      factors in the crystallization of the present-day malaria resurgence in Bombay.
      The paper concludes by arguing that malaria in urban India is a serious problem
      that cannot be neglected. In the case of Bombay, the solution to the crisis can
      be found, in part, by reexamining the historical and political issues that have
      determined the nature and magnitude of the problem over the last century.

PMID- 11234325
TI  - Malaria control in East Africa: the Kampala Conference and the Pare-Taveta
      Scheme: a meeting of common and high ground.
AB  - The 1950 Malaria Conference in Equatorial Africa, held in Kampala, Uganda, has
      been remembered primarily for its decision to control malaria '...by modern
      methods as soon as feasible, whatever the original degree of endemicity, and
      without awaiting the outcome of further experiments.' This decision was far from
      conclusive and, indeed, reflects only one side of the argument which brought two
      groups of malariologists into direct opposition on the wisdom of malaria control
      in equatorial Africa, using modern methods such as DDT. Through an examination of
      the unpublished verbatim transcript of the Kampala Conference, we are able to
      document the 'furious debates' which took place at Kampala in 1950. We highlight,
      in particular, the adamant concerns expressed by some of the delegates that
      intervention in areas of high malaria transmission might lead to a loss of
      naturally acquired immunity which, in turn, could give rise to a resurgence of
      malaria, should the control strategies fail to be sustained. As we show, this
      concern had been expressed by a number of malariologists working in East Africa
      in the first half of the twentieth century, but it was only with the advent of
      DDT, as a residual insecticide, that the implications of wide-spread control, in
      the absence of any knowledge of the long-term consequences, became a serious
      possibility. While the Kampala Conference gave the 'go ahead' to control malaria
      in Africa without awaiting the outcome of 'further experiments', a number of
      participants insisted that a field trial should be set up to evaluate the impact
      of malaria on areas of high transmission both before and after spraying: to this
      end, a field trial in Pare-Taveta was carried out in 1954-59. In this paper we
      look at the Kampala Conference for its scientific debates and the Pare-Taveta
      Scheme for its field applications. In the final part of the paper, we address a
      number of questions raised at Kampala which have, once more, become contentious
      issues, following the recent successful trials of ITBNs. We believe that an
      understanding of the historical foundations of these issues should provide an
      important component of the new WHO campaign to Roll Back Malaria.

PMID- 11234326
TI  - Criticism of WHO's revised malaria eradication strategy.
AB  - Fred L. Soper played a key role in promoting the idea that malaria could be
      eradicated world-wide. He believed eradication to be feasible based on the
      ability of household insecticide spraying to interrupt malaria transmission. He
      opposed WHO's strategy to reduce the number of years devoted to spraying and to
      rely instead on chemotherapy to wipe out remaining foci of malaria. While his
      criticism was intense, it neither featured in the discussions of the World Health
      Assembly nor the WHO malaria Expert Committee. The author concludes that had his
      criticism been heard the global campaign could have been stopped far earlier than
      in fact it was. Furthermore, failure to openly address Soper's criticism
      represented a major failure on the part of the WHO Secretariat to ensure that
      policy decisions reflected a full consideration of all underlying issues,
      technical or otherwise.

PMID- 11234327
TI  - The malaria vaccine: seventy years of the great immune hope.
AB  - The cluster of seminal microbiological discoveries at the end of the 19th century
      through to the first quarter of the 20th century gave rise to the expectation
      that the control of malaria would be by scientific technology (as opposed to the
      'brute force' of bonification/massive engeneering works) and that technology
      would be immunization by a malaria vaccine. Immunology's foundation was in
      microbiology and the two related disciplines matured concurrently. Immunization
      with dead or inactivated microorganisms became immunology's strongest arm,
      affording protection against many major diseases such as smallpox, anthrax,
      rabies, yellow fever and tetanus. So why not malaria? In the pre-World War II era
      there were no chemotherapeutic/prophylactic drugs practical for the control of
      malaria and a vaccine seemed the easy, rational path to that objective. From 1910
      to about 1950 there were numerous attempts in humans and primate and avian models
      to devise a malaria vaccine. However, it soon became apparent that the malaria
      parasites, because of their complex, stage-specific antigenic identity as well as
      their relatively poor immunogenicity, would be much more difficult to use as a
      vaccine than the bacteria or viruses. There were some experimental successes, but
      none in humans.

PMID- 11234328
TI  - Malaria in inter-war British India.
AB  - British India was an important site of much important malaria research. Although
      Ronald Ross left India in 1899, a number of malariologists continued the task of
      evaluating the incidence and distribution of malaria in the country. Implementing
      practical solutions was hampered by formidable social and economic problems. This
      paper examines the Indian situation in the late 1920s, through a retrospective
      selection of writings chosen by J.A. Sinton for reproduction in an early issue of
      'The records of the malaria survey of India', and the analysis of the Indian
      malaria situation through a visit of the League of Nations Malaria Commission in
      1929.

PMID- 11234329
TI  - Dealing with malaria in the last sixty years: aims, methods and results.

PMID- 11234330
TI  - Wartime research on malaria chemotherapy.
AB  - Malaria was a major problem for the opposing forces in World War II. During the
      first year of operations in the South West Pacific the casualties caused by this
      disease greatly exceeded the numbers of battle casualties. In response to this
      situation comprehensive research and development programs to discover new
      antimalarial drugs were undertaken in the United States and Britain. In both
      countries compounds synthesised by co-operating chemical laboratories were
      screened against bird malaria and those with high activity and low toxicity were
      tested in man. The wartime program in America was funded by the Office of
      Scientific Research and Development and co-ordinated through a specially
      designated body under the Committee on Medical Research of the National Research
      Council. It was an enormous undertaking involving a massive co-operative effort
      between pharmacologists, chemists, and clinical research scientists from American
      universities, the US Public Health Service, and the laboratories of commercial
      pharmaceutical companies. The British program, on a much smaller scale, was based
      on a co-operative arrangement between the research laboratories of Imperial
      Chemical Industries at Manchester, the Liverpool School of Tropical Medicine and
      the British Medical Research Council. The wartime programs in both countries
      identified a number of promising leads but lacked the resources to permit their
      rapid clinical evaluation against field strains of human malaria. This deficiency
      was overcome by experiments conducted by the Land Headquarters Medical Research
      Unit of the Australian Army in Cairns, Queensland with the use of army
      volunteers. Large scale clinical trials of the most promising compounds which
      emerged from the American and British programs were carried out in Australia.
      This co-operative endeavour among allied scientists resulted in a range of new
      drugs which have had an enduring influence on malaria chemotherapy.

PMID- 11234332
TI  - Malaria and World War II: German malaria experiments 1939-45.
AB  - The epidemiological and pharmacological fight against malaria and German malaria
      research during the Nazi dictatorship were completely under the spell of war. The
      Oberkommando des Heeres (German supreme command of the army) suffered the bitter
      experience of unexpected high losses caused by malaria especially at the Greek
      front (Metaxes line) but also in southern Russia and in the Ukraine. Hastily
      raised anti-malaria units tried to teach soldiers how to use the synthetic
      malaria drugs (Plasmochine, Atebrine) properly. Overdoses of these drugs were
      numerous during the first half of the war whereas in the second half it soon
      became clear that it would not be possible to support the army due to
      insufficient quantities of plasmochine and atebrine. During both running fights
      and troop withdrawals at all southern and southeastern fronts there was hardly
      any malaria prophylaxis or treatment. After war and captivity many soldiers
      returned home to endure heavy malaria attacks. In German industrial (Bayer, IG
      Farben) and military malaria laboratories of the Heeres-Sanitats-Akademie (Army
      Medical Academy) the situation was characterised by a hasty search for proper
      dosages of anti-malaria drugs, adequate mechanical and chemical prophylaxis
      (Petroleum, DDT, and other insecticides) as well as an anti-malaria vaccine. Most
      importantly, large scale research for proper atebrine and plasmochine dosages was
      conducted in German concentration camps and mental homes. In Dachau Professor
      Claus Schilling tested synthetic malaria drugs and injected helpless prisoners
      with high and sometimes lethal doses. Since the 1920s he had been furiously
      looking for an anti-malaria vaccine in Italian mental homes and from 1939 he
      continued his experiments in Dachau. Similar experiments were also performed in
      Buchenwald and in a psychiatric clinic in Thuringia, where Professor Gerhard Rose
      tested malaria drugs with mentally ill Russian prisoners of war. Schilling was
      put to death for his criminal research in 1946, Rose was condemned to lifelong
      imprisonment in 1947, though, not for his malaria research but for his dreadful
      experiments with epidemic typhus sera which he also had performed in
      concentration camps and with prisoners of war in Russia.

PMID- 11234333
TI  - Technology and malaria control, 1930-1960: the career of Rockefeller Foundation
      engineer Frederick W. Knipe.
AB  - Frederick W. Knipe was a malaria-control engineer with the Rockefeller
      Foundation, serving in Bulgaria, Albania, India, Mexico, Italy, and the United
      States. There were two phases to his career: from 1930 to 1943 he focused on
      drainage works that reduced or eliminated mosquito habitat, and from 1944 to 1960
      he supervised DDT spraying programs. His appointments to the WHO Expert Committee
      on Insecticides, 1948-55, demonstrate that his contributions to malaria-control
      were highly regarded by his peers.

PMID- 11234331
TI  - The United States Army and malaria control in World War II.
AB  - The United States Army faced difficult malaria control problems both at home and
      abroad during World War II. This challenge forced the Army to develop new tools
      and strategies for use in malarious areas where fighting was occurring. Due to
      the severe malaria problems being faced in some combat areas and the need to
      solve these problems quickly, intensive malaria research and operational programs
      were developed and implemented. With these concerted efforts and the simultaneous
      development of new control technologies, malaria was successfully controlled in
      most locations. In order to accomplish this high level of control both in the US
      and overseas, the Army developed a very organized approach to the malaria problem
      and implemented it in an effective manner. The creation of new technical
      solutions was also strongly emphasized and out of this effort came the
      development of effective antimalaria drugs to replace quinine, of new
      insecticides and of more effective systems for delivering these insecticides.
      Some of the major new tools which came out of this research were DDT and drugs
      such as Atabrine and chloroquine. The availability of Atabrine and DDT
      revolutionized malaria control throughout the world. The knowledge and experience
      gained through the use of these new tools by the US Army and other agencies in
      World War II provided the basis for a new optimism regarding malaria control
      which then led to the development of the global malaria eradication strategy in
      the post-war years.

PMID- 11234334
TI  - Malaria and social movements in Mexico: the last 60 years.
AB  - The Mexican Ministry of Health's anti-malaria campaigns of the last sixty years
      have overlapped and interacted with both the World Health Organization's Global
      Eradication Program and a series of major political, social, and demographic
      movements in Mexico, including economic transformation, migration, urbanization,
      tourism, rural development, and the building of social and sanitary services. The
      authors argue that three decades of successful environmentally-oriented malaria
      work that integrated social and economic development was followed by the Global
      Campaign's insecticide-based approach that failed in both its economic and public
      health objectives, ultimately serving to block development efforts, particularly
      in poorer and southern states.

PMID- 11234335
TI  - Dealing with malaria in the last 60 years. A personal experience.
AB  - Dealing with malaria in the last 60 years is seen by the author in the
      perspective of his own experience. His malaria work, which began in 1941, covered
      the study of the habits of the mosquitoes dwelling in the savanna country of
      Eastern Colombia and the effect on malaria transmission of the newly introduced
      DDT residual spraying. The success of the campaign he later directed in Sarawak
      and Brunei contributed to the launching by WHO of its global malaria eradication
      campaign. Further successful work in Uganda showed the possibility of effective
      control and even eradication in highland country but left unsolved the problem of
      how to interrupt transmission of holoendemic malaria in Africa. The author's work
      with WHO in the Middle East showed to what extent social and economic conditions
      could influence the course of a malaria campaign. This was also the experience in
      America, both in Colombia in the author's early work and later in Mexico during
      an evaluation of the national malaria programme. Development of insecticide
      resistance was also encountered in his career and the refractoriness of the
      European vectors was also observed in his work as a malariologist.

PMID- 11234336
TI  - Epidemiology in the strategies for malaria control.
AB  - A rapid overview is presented of the evolution of the main orientations of
      malaria control, since the discovery of mosquito transmission. Stated control
      objectives appear to have oscillated between expectations to eradicate the
      vector, or at least the disease, and more modest approaches to minimise the
      effects of the infection. High optimism was raised when a new control measure, or
      new combination of existing measures, appeared to be highly effective and was
      expected to have universal applicability. The implementation of large scale
      campaigns eventually found the limits of applicability of the proposed strategy
      and the exaggerated expectations soon gave way to disillusion and, eventually, to
      a revival of research. The longest and most impacting period of exaggerated
      expectations was the global malaria eradication campaign of the 1950s and 1960s,
      which completely disregarded the study of local epidemiology, considering that
      all it was needed was to know if an area was "malarious" or not. Research was
      practically abandoned and, even when reinstated after the recognised failure of
      the campaign, it has retained an almost exclusive orientation towards the
      development of control tools, drugs or eventually vaccines. One of the earliest
      victims of the eradication campaign was the study of epidemic malaria and its
      determinants in different epidemic prone areas. In spite of an extremely long
      period of disillusion, lasting for almost two decades, the reality of the malaria
      problem led WHO and member countries to agree on a global strategy of control,
      aiming at a realistic use of existing tools, to at least reduce or prevent
      mortality. An essential element of this strategy is the prevention or control of
      malaria epidemics and the selective use of vector control, both of which have to
      be based on a solid knowledge of local epidemiology, the study of which has to
      rejoin the path abandoned fifty years ago.

PMID- 11234337
TI  - Quinine (Cinchona) and the incurable malaria: India c. 1900-1930s.
AB  - The early decades of this century witnessed significant developments in the
      approaches to control of malaria in British India. These included both large
      scale preventive measures and curative treatment methods (often referred to as
      "cinchona" or "quinine" policy). This paper identifies a number of factors that
      constrained the colonial government's capacity to control malaria through
      effective cinchona policy. The ideal of achieving "self-sufficiency" and having
      an efficient form of treatment and distribution within the reach of the masses in
      India (as originally intended in late 1850s) was far from being achieved. Both
      government's policy and medical profession seemed to have contributed equally to
      this failure.

PMID- 11234338
TI  - Design of semicarbazones and their bio-isosteric analogues as potential
      anticonvulsants.
AB  - A series of semicarbazones and hydrazones were prepared and evaluated for
      anticonvulsant activity. Some compounds provided significant protection against
      maximal electroshock (MES) and subcutaneous strychnine induced seizures (ScSty).
      Compound 2a emerged as the most active compound at a dose of 30 mg/kg in ScSty
      test. The compounds 1a, 1g and 2a-e showed significant potentiation of sedative
      and hypnotic activity of pentobarbitone sodium. Thus compound 2a could serve as a
      prototype for future developments.

PMID- 11234339
TI  - Modulation of intercalating properties of pyrido[1,2-e]purins via side-chain
      modifications: NMR and MD studies.
AB  - Two pyrido[1,2-e]purins with different side chain lengths have been synthesized
      to test their ability to intercalate inside DNA. The interactions of these drugs
      with synthetic oligodeoxy nucleotide d(CGATCG)2 have been studied with 1H and 31P
      NMR spectroscopy experiments. Molecule 1, rather amphiphilic (Log(P) = 1.3, due
      to its hydroxypropyl side chain) can intercalate GC sites of the mini helix,
      under a fast exchange mechanism and a 2:1 stoechiometry. The presence of a six
      methylen side chain in 2 (hydroxyhexyl side chain) is responsible for a
      relatively poor solubility of this molecule in water (log P = 2.3). Binding,
      rather than intercalation, of 2 to the external GC pairs is observed, severely
      limited by the formation of aggregates. Models for the intercalation of 1, are
      proposed using energy minimizations and Molecular Dynamics (MD) calculations
      subject to restraints from experimental nOe connectivities. Simulations and
      experiments both indicate fast exchange of 1 in its intercalation site.

PMID- 11234341
TI  - [Ring cleavage of N-arylpyridinium salts by nucleophiles--regioselectivity and
      stereochemistry of the products. 1].
AB  - The N-arylpyridinium salts 1, 5 und 10 generate with hydroxylamine a ring
      cleavage to the E/Z-oximes of the (2E,4E)-5-aminopentadienals 2, 6 und 11. With
      the 3-methylpyridinium derivative 12 the described regiospecifity of the reaction
      with nucleophiles is disproved. The attack by hydroxylamine is realized to a
      nearly equal degree at C-2 and C-6. As 2-methyl substituted products the E-oximes
      of (2E,4E)- and (2Z,4E)-5-aminopentadienal result, while as 4-methyl substituted
      products the E/Z-oximes of (2E,4E)-5-aminopentadienal are generated. Just so with
      the hydroxide ion as nucleophile from 12--in contrast to the literature--both
      position isomer 5-aminopentadienals are formed. They were characterized as 15 and
      16. The quaternized product of nicotine 22 shows ring opening with hydroxide ion,
      not at C-2 as described formerly, but only at 6-position and gives rise to the 4
      (N-methylpyrrolidinyl) substituted 5-aminopentadienal 23. By hydroxylamine only
      the E/Z-oxime mixture of the 4-substituted 5-aminopentadienal 25 is formed, which
      can be dehydrated to the nitrile 27.

PMID- 11234340
TI  - Synthesis and properties of 2-(4-substituted)butyl derivatives of some 2,3
      dihydro-1,3-dioxo-1H-pyrrolo[3,4-c]pyridines.
AB  - The synthesis of 2-(4-substituted)butyl derivatives of 4-alkoxy-2,3-dihydro-6
      methyl-1,3-dioxo-1H-pyrrolo[3,4-c]pyridine (10-15) and the results of preliminary
      pharmacological screening are described in this paper. All the compounds tested
      showed a strong analgesic action, suppressed spontaneous locomotor activity and
      prolonged barbiturate sleep. Except 10, all significantly decreased systolic and
      diastolic blood pressure.

PMID- 11234342
TI  - Vilsmeier formylation of praziquantel: synthesis and application for
      polarographic assay.
AB  - A simple and sensitive method for the polarographic determination of praziquantel
      (1) after derivatization using Vilsmeier formylation is described. The
      polarographically active compound obtained by this procedure has been separated,
      identified and prepared using N,N-dimethylformamide and phosphorus oxychloride.

PMID- 11234343
TI  - Spectrophotometric and HPLC determination of fleroxacin in tablets.
AB  - The paper describes and compares spectrophotometric and HPLC determination of
      fleroxacin in commercial tablets. The optimum conditions for spectrophotometric
      assay were found to be at pH < 3.5 (0.1 M HCl) at a wave length of 286 nm. HPLC
      analysis was carried out on a Beckman ODS 5 microns column in a pH 3 phosphoric
      acid solution (detector wave length 254 nm).

PMID- 11234344
TI  - A simple method for the identification and assay of iopamidol and iothalamate
      meglumine in pharmaceutical samples based on proton nuclear magnetic resonance
      spectroscopy.
AB  - A proton nuclear magnetic resonance (PMR) spectroscopic method is described for
      the direct assay and identification of the triiodinated radiographic contrast
      agents iopamidol (nonionic type) and iothalamate meglumine (ionic type) in
      commercial solutions and as a bulk material. Samples were prepared by simply
      diluting an injectable solution with or dissolving a powdered sample in D2O.
      Sodium acetate was added to serve as an internal standard. Quantitations were
      based on the resonance signals for the protons of the CH3-CO-group at 1.58 ppm
      (iopamidol) or 2.25 ppm (iothalamate), CH3-N-group at 2.38 ppm (meglumine) and
      CH3-CO-group at 1.92 ppm (acetate). The mean +/- SD (n = sets of 10 samples each)
      recovery of iopamidol, iothalamic acid and meglumine from synthetic mixtures with
      the internal standard were 99.6 +/- 0.63, 99.7 +/- 0.66 and 99.9 +/- 1.18%,
      respectively; with the values ranging from 98.7-100.9% for iopamidol and
      iothalamate, and from 98.3-100.8% for meglumine.

PMID- 11234345
TI  - The use of information theory and numerical taxonomy methods for evaluating the
      quality of thin-layer chromatographic separations of flavonoid constituents of
      Matricariae flos.
AB  - A methanol extract of Matricariae flos was analysed with regard to the flavonoid
      composition. Rational selection of a restricted set from eight chromatographic
      systems tested for the separation of these compounds is discussed. Series of
      mathematical techniques for the evaluation of solvents and solvent combinations
      in thin-layer chromatography of flavonoid constituents have been explored. The
      chromatographic systems are classified according to their mutual resemblance by
      numerical taxonomy techniques. The selection criterion in the groups, obtained by
      numerical taxonomy classification, is the information content or the
      discriminating power. The most suitable mobile phases for TLC separation of
      flavonoid constituents of Matricariae flos are: ethylacetate-methanol-water
      (75:15:0 v/v), ethylacetate-formic acid-water (80:10:10 v/v) and ethylacetate
      formic acid-acetic acid-water (100:11:11:27 v/v).

PMID- 11234346
TI  - Studies on gynaecological hydrophilic lactic acid preparations. Part 4: Effects
      of polyvinyl pyrrolidone K-90 on properties of methylcellulose gels.
AB  - In continuing the investigation of the binding of lactic acid with basic polymers
      polyvinyl pyrrolidone K-90 (PVP) was used. Use of PVP in mixtures with lactic
      acid in experimentally determined and calculated proportions allowed the
      preparation of gels with pH 3.8-4.4, i.e. maintaining the physiological
      conditions in the vagina. The viscosity of the methylcellulose gels increases
      proportionally to the amount of the PVP--lactic acid complex added. Examination
      of the gels in the biopharmaceutical model, which simulated the physiological
      conditions of the vagina, allowed determination of the mobility of the
      preparations in patients.

PMID- 11234347
TI  - Effect of drug solubility on in vitro availability rate from suppositories with
      polyethylene glycol excipients.
AB  - Factors involved in the availability mechanism of different drugs from
      suppositories with polyethylene glycol (PEG) excipients were studied using an in
      vitro model of the rectal compartment with a porous membrane simulating the
      rectal barrier. Different from lipophilic excipients, the drug is released as a
      consequence of the progressive dissolution of PEG into the intrarectal aqueous
      phase. Drug concentration in this small intrarectal phase produces the gradient
      against the large volume of the plasmatic phase, which regulates the diffusion
      rate through the barrier. As with lipophilic excipients, drug solubility in water
      was found to be an important factor influencing suppository release rate.
      Nevertheless, PEG influenced in vitro drug availability considerably, by
      increasing both drug solubility and dissolution rate. The osmotic effect of PEG
      in the intrarectal compartment influenced the increase in volume of the aqueous
      phase. The results, compared with those obtained from suppositories with a
      lipophilic excipient, show a higher dissolution rate from PEG excipient, but a
      higher diffusion rate across the barrier did not always correspond. Drugs less
      soluble in water showed a greater availability from PEG suppositories. On the
      contrary the more soluble drugs were less available.

PMID- 11234348
TI  - Cytotoxicity of 2-ethenyl-2,3-dihydrophthalazine-1,4-diones in murine and human
      tumor cultured cells.
AB  - 2-Etheny1-2,3-dihydrophthalazine-1,4-diones were successfully synthesized and
      proved to be effective cytotoxic agents against the growth of suspended murine
      and human leukemias and lymphomas. Selected compounds were also active in human
      HeLa uterine carcinoma, suspended effusion breast MCF-7 and glioma HS683 screens.
      These agents suppressed P388 lymphocytic leukemia DNA synthesis after 60 min at
      100 microM. Their target appeared to be the de novo synthesis pathway with
      significant inhibition of the activities of both regulatory enzymes of the
      pathway, i.e. PRPP-amide transferase and IMP dehydrogenase resulting in a
      reduction in the d[NTP] pool levels for DNA incorporation. The compounds did not
      affect de novo pyrimidine synthesis and its regulatory enzymes. Very minor
      reduction by the agents was noted for the nucleoside kinases and the DNA and RNA
      polymerase activities within 60 min. DNA was not a target of the agents in that
      there was no alkylation of the nucleotide bases, intercalation between base pairs
      or cross-linking of the DNA strands; however, the agents did cause P388 DNA
      strand scission after 24 h at 100 microM.

PMID- 11234349
TI  - Norditerpenic ester and pentacyclic triterpenoids from root bark of Calotropis
      procera (Ait) R. Br.
AB  - A new norditerpenyl ester, named Calotropterpenyl ester, and two unknown
      pentacyclic triterpenoids, namely calotropursenyl acetate and calotropfriedelenyl
      acetate have been isolated from the root bark of Calotropis procera. Their
      structures have been established as 6,10,14-trimethylpentadec-6-enyl
      2',4',8',12',16'-pentamethyl nonadecane ester, urs-12,19(29)-diene-3 beta-yl
      acetate and friedelin-1-ene-3 beta-yl acetate, respectively, on the basis of
      spectral data analyses and chemical reactions.

PMID- 11234350
TI  - Iridoids from Phlomis umbrosa.
AB  - Two epimeric pairs of iridoid aglycones, named shanzhigenin methyl ester and 1
      epishanzhigenin methyl ester, and 8-acetylshanzhigenin methyl ester and 8-acetyl
      1-epishanzhigenin methyl ester, were isolated from Phlomis umbrosa roots, along
      with five known iridoid glucosides. The four iridoid aglycones are reported for
      the first time from a natural source. Their structures were established by
      spectroscopic methods, mainly 1D- and 2D-NMR spectroscopic experiments, and
      chemical methods.

PMID- 11234351
TI  - Synthesis of some new neostigmine methyl sulphates and related compounds.

PMID- 11234352
TI  - [Condensation of dihydro-1,4-benzoquinone derivatives with 1,2-arylenediamines].

PMID- 11234353
TI  - Pulse polarographic determination of meloxicam.

PMID- 11234354
TI  - Flow injection analysis of meloxicam using UV-detection.

PMID- 11234355
TI  - The application of pig blood in the in vitro measurement of platelet adhesion.

PMID- 11234356
TI  - Cytotoxic alkaloids from Tylophora indica.

PMID- 11234357
TI  - Mutagenic and carcinogenic constituents of medicinal herbs used in Europe or in
      the USA.

PMID- 11234358
TI  - Study defines success factors for capitated organizations.

PMID- 11234359
TI  - How one organization is making it big with global capitation.
AB  - Can you win big with global capitation? Yes, says JSA Associates, but you have to
      know what you're doing and choose your partners carefully.

PMID- 11234360
TI  - Go beyond demographics to get a handle on pharmacy costs.
AB  - Relying on demographic information to predict drug costs when developing a
      capitation rate just won't cut it. Look instead to plan characteristics.

PMID- 11234361
TI  - Physician group precertifies physical therapy to cut utilization.
AB  - What can you do when you see that there's no rational basis for the number of
      physical and occupational therapy visits being approved, and your capitation
      dollars are leaking like a rusty bucket? If you develop guidelines based on
      diagnoses and pre-certify, you can save big bucks.

PMID- 11234362
TI  - Give physicians incentives to deliver value, boost outcomes.
AB  - The secret of success under capitation for this New England physician group is to
      pay physicians extra for delivering value. Here's how they determine who gets the
      money.

PMID- 11234363
TI  - MGMA data reveal higher revenues for heavily capitated groups.
AB  - Is there money in capitation? You bet. This Data Insight shows that the
      multispecialty groups with the highest revenue and charges are those with the
      greatest percentage of capitation.

PMID- 11234364
TI  - Plans in two states must disclose payment methodology.
AB  - What happens when physicians know the maximum a plan will pay for a service? Do
      they use that information to become better negotiators or do they automatically
      charge the max? A court decision could provide an answer.

PMID- 11234365
TI  - New sparks over electroshock.

PMID- 11234366
TI  - Against the grain.

PMID- 11234367
TI  - [Structure of alpha-spiral hairpins with short connections in globular proteins].
AB  - The analysis of conformations of more than 100 alpha-alpha-hairpins with closely
      packed helical segments and connections up to four amino acid residues in length
      was carried out. Five types of the connections were revealed and their phi and
      psi values on the Ramachandran map were found. Each type of alpha-alpha-hairpins
      was shown to have a unique sequence pattern for hydrophobic and hydrophilic
      residues.

PMID- 11234368
TI  - [Interaction of DNA with benzocrown derivatives of actinocin].
AB  - Complexes of DNA with actinocin derivatives containing benzocrown groups at the 1
      and/or 9 positions of the chromophore were studied by spectrophotometric
      titration and circular dichroism. The actinocin chromophore and the crown
      fragments are the binding sites of the ligands with DNA. The mode of ligand-DNA
      binding is shown to depend on the size of the crown group, its distance to the
      actinocin chromophore, and the ionic strength of the medium. Selective toward Na+
      ion benzocrown fragments combine with DNA phosphate groups. The simultaneous
      interaction of the actinocin chromophore with the DNA bases is possible only at
      optimal distance between both the binding sites of ligand molecule.

PMID- 11234369
TI  - [Calculation of DNA condensation, caused by adsorption of ligands].
AB  - A method for calculating the curves of DNA transition from linear to condensed
      state upon binding of condensing ligands has been developed. The character of the
      transition and ligand concentration necessary for condensation have been shown to
      be governed by the length of DNA molecule, energy and stoichiometry parameters of
      DNA-ligand complex (equilibrium constant between linear and condensed form in the
      absence of ligands, constants for ligand binding to linear and condensed forms,
      the number of base pairs covered by one ligand, etc.). The results of the
      calculations indicate that only slight difference in the free energies of these
      states in free DNA (less than 6 cal/mole(bp) for DNA of 500 bp long) is
      sufficient for the existence of stable linear state in the absence of ligands (in
      free DNA) and the formation of stable condensed state upon complexation.

PMID- 11234370
TI  - [Amplification of transcription of separate mitochondrial genes in human and
      monkey B-cell non-Hodgkin's lymphoma].
AB  - Mitochondrial genes that are overexpressed in human and monkey B-cell non-Hodgkin
      lymphomas (B-NHLs) were sought via subtraction hybridization, cloning, and
      differential screening of the resulting cDNA libraries. The cDNAs of
      mitochondrial genes made an appreciable proportion of all lymphoma-specific
      cDNAs. Lymphomogenesis was associated with overexpression of a mitochondrial gene
      set which varied with lymphoma type and always included NADHIV. A possible
      association between overexpression of certain mitochondrial genes and cell
      malignant transformation is discussed.

PMID- 11234371
TI  - [Comparative characteristics of transcription of genes for alpha and beta
      lymphotoxin subunits in B- and T-lymphocyte lines, in peripheral lymphocytes, and
      in normal human tissue].
AB  - Membrane lymphotoxin (LT) is heterotrimer LT alpha 1 beta 2, and its production
      depends on two genes. Northern blotting was employed in studying their
      transcription in B- and T-lymphoma cell lines and in peripheral blood lymphocytes
      before and after induction with phorbol myristate acetate (PMA). Transcription of
      either gene proved similarly regulated in several cell lines and in blood
      lymphocytes. Activation of the LT alpha gene was associated with induction of
      transcription factor NF-kappa B (p50/p65) upon cell treatment with PMA. On
      evidence of RT-PCR, two transcripts of the LT beta gene occurred in equimolar
      amounts in all lymphoid cells. A product of alternative splicing contained an
      open reading frame coding for the cytoplasmic portion of LT beta.

PMID- 11234372
TI  - [Two forms of precursors of a heparin-binding EGF-like growth factor-diphtheria
      toxin receptor].
AB  - A new mRNA coding for the heparin-binding EGF-like growth factor (HB-EGF) was
      found in Vero cells. The corresponding cDNA had C-156 in place of T, which
      resulted in a loss of the NheI site and a substitution of Leu-33 with Pro in the
      HB-EGF precursor. The known and new forms of the precursor were accordingly
      termed L and P. A possible conformational change in the corresponding propeptide
      region were assumed to affect processing of soluble secreted HB-EGF. The L and P
      mRNAs are differently expressed in various cell lines and have the identical 5'
      untranslated sequences. Possibly, they are transcribed from one promoter and then
      alternatively spliced. Stimulation of resting Vero cells with tetraphorbol ester
      (TPA) substantially increased production of the L form, decreased production of
      the P form, and did not affect expression of the total HB-EGF mRNA. This was
      associated with an increase in binding of the diphtheria toxin, suggesting that
      the L HB-EGF precursor acts as its receptor.

PMID- 11234373
TI  - [Connection of the polymorphic variant T174M angiotensinogen gene with coronary
      atherosclerosis in the Tomsk population].
AB  - Allele and genotype frequencies of the T174M polymorphism of the angiotensinogen
      gene were for the first time estimated in the West Siberian population. The
      polymorphism was tested for association with coronary atherosclerosis (CAS) and
      with several quantitative risk factors in patients with angiographically verified
      CAS, healthy individuals, and in a population sample nondifferentiated with
      respect to CAS.

PMID- 11234375
TI  - [Genetic variability of Iris setosa].
AB  - Genetic variability of Iris setosa Pall. ex Link. was studied by the RAPD method.
      Plants from three different habitats were compared by 135 loci revealed with
      eight arbitrary primers. The three plant accessions all exhibited a high level of
      polymorphism, and each was characterized by different frequencies of polymorphic
      fragments, which probably reflected the geographic isolation of the analyzed
      populations. The average level of polymorphism detected was 35%.

PMID- 11234374
TI  - [Construction of peptide mimetics of an epitope of the human immunodeficiency
      virus (HIV-1) gp41 protein, recognized by virus-neutralizing antibodies 2F5].
AB  - A phase peptide library was screened with virus-neutralizing monoclonal
      antibodies (MCA) 2F5 which recognize a conserved epitope of HIV-1 gp41. Phages
      that expose peptides specifically binding with MCA 2F5 were selected by ELISA.
      Amino acid sequence analysis revealed a homology to region 662-671 of HIV-1 HB10
      gp160 for most peptides. The major role in recognition was ascribed to Asp-664,
      Lys-665, and Trp-666. The epitope-mimicking peptides were tested for
      immunogenicity. Antibodies to gp41 were detected in serum of immunized rabbits.

PMID- 11234376
TI  - [Expression of the NS1 gene of tick-borne encephalitis virus in gram-negative
      bacteria from the mouse nasopharynx].
AB  - Bacteria were isolated from the nasopharynx of BALB/c mice and electroporated
      with pUR290(NS1)2 containing two copies of tick-borne encephalitis virus (TBEV)
      strain Sofjin NS1 under the control of the lac promoter. The plasmid persisted in
      transformants for at least ten passages. The NS1 gene expression was detected in
      Gram-negative enterobacteria via immunoblotting with monoclonal antibodies
      against TBEV nonstructural glycoprotein NS1. Recombinant NS1 was detected in
      bacterial cells and in the culture medium. Intranasal immunization with
      recombinant bacteria activated production of antibodies against NS1 in serum of
      BALB/c mice. The humoral immune response to NS1 failed to protect immunized mice
      from a TBEV challenge.

PMID- 11234377
TI  - [Intranuclear ion fountains as regulators of genome work: fountain hypothesis of
      dominance and some epigenetic effects].
AB  - It is hypothesized that gene function is modulated through the action of the ion
      channels of the internal nuclear membrane, and that this underlies the phenomenon
      of dominance and some epigenetic effects. The topographic specificity essential
      to gene regulation by injecting portions of ions--ion fountains--is ensured by
      special fountain RNAs (fRNAs), which operate as double-stranded molecules, and
      fions, the fRNA-binding sites on the DNA. Every specific fion.fRNA complex then
      binds with the protein of an ion channel in the inner nuclear membrane, whereby
      this channel briefly opens to dispense, e.g., Ca2+, Zn2+, or K+ from the
      perinuclear cistern into the nucleus, as defined by the specificity of fRNA,
      fion, and the channel chosen by them. Fions may be situated both in introns of
      genes and at their flanks, even quite far from the target gene. Allelic fions,
      that is, fions located in homologous sites of homologous chromosomes but
      differing in the capacity of binding different fRNAs, will unequally influence
      the ionic surroundings of their structural genes. Ion channels can provide the
      dominant allele with an ionic atmosphere dissimilar from that of the recessive
      allele. Distinctions in the nature, number, and location of fions may be the main
      reason why the dominant and recessive alleles of a structural gene differ in
      activity even though their other properties are identical. Unequal changes
      occurring in the vicinity of the alleles may involve chromatin configuration,
      transcriptional activity of the gene, mRNA processing and lifespan. Isolation of
      structural genes in a chromosome by long intergene spacers, and large distances
      between chromosomes in the nucleus prevent undesirable interference of ion
      fountains. Fions may be key components of many enhancers and silencers. The
      performance of fions may be affected by pairing of homologous nucleotide
      sequences of chromosomes, which generates a number of epigenetic effects, such as
      transvection and gene position effect. Excessive approach of a structural gene to
      inadequate ion fountains may cause unscheduled chromatin compaction and gene
      suppression.

PMID- 11234378
TI  - [Molecular structure of the locus for sucrose utilization by Lactobacillus
      plantarum: comparison with Pediococcus pentosaceus].
AB  - Structure of the sucrose utilization locus in a Lactobacillus plantarum type
      strain was studied using PCR and Southern hybridization. Restriction map analysis
      revealed its high similarity to the sequenced sucrose utilization locus of
      Pediococcus pentosaceus pSRQ1. The L. plantarum locus proved containing
      oppositely oriented scrA and the scrBRagl operon, but not agaS. The L. plantarum
      sucrase gene (scrB) was partly sequenced. A higher (98.6%) homology was revealed
      between scrB than between the 16S rRNA genes of L. plantarum and P. pentosaceus,
      suggesting horizontal transfer of the sucrose utilization locus between the
      genera of lactic acid bacteria. Amino acid sequence analysis showed that the ScrB
      proteins of the two species belong to a subfamily of glycosyl hydrolase family
      GH32 which includes various beta-fructosidases.

PMID- 11234379
TI  - [Organization of extended repeats in heterochromatin in sex chromosomes in the
      common vole species Microtus group "arvalis"].
AB  - Two long repeats, MS3 and MS4, are predominantly located in sex-chromosomal
      heterochromatin in common vole species. Their tandem arrangement was revealed by
      means of the PCR analysis of genomic DNAs of four Microtus species and by
      restriction mapping of clones selected from a M. rossiaemeridionalis genomic
      library. Several mobile elements proved incorporated in a monomeric unit of each
      repeat and amplified together with its other components. In addition, LINE
      inserts were found in MS4 tandem arrays. The copy number of both repeats per
      haploid genome was estimated at 100-300 for euchromatin and 20,000-40,000 for the
      M. rossiaemeridionalis genome. The repeats were assumed to be the major component
      of sex-chromosomal heterochromatin DNA.

PMID- 11234380
TI  - [Minicircular kinetoplast DNA from Trypanosomatidae].
AB  - Analysis of primary structure and organization of mitochondrial (kinetoplast) DNA
      of flagellates occupies a prominent place in the studies of eukaryote
      mitochondrial genomes, owing to its unusual organization and functioning as well
      as to the epidemiological role of the Trypanosomatidae family. According to
      contemporary notions, living zooflagellates are direct descendants of the
      ancestral forms that gave rise to all eukaryotic kingdoms. Hence, comparative
      mtDNA studies of recent Trypanosomatidae open broad prospects for phylogenetic
      reconstructions and analysis of presumable routes of eukaryote evolution. The
      structure, characteristics, and functions of Trypanosomatidae minicircular
      kinetoplast DNA are discussed here.

PMID- 11234381
TI  - [Tissue-specific splicing of 5'-exons of the Oct-1 transcription factor gene].
AB  - It has been shown that pro-mRNA of transcription factor Oct-1 undergoes the
      tissue-specific splicing. The Oct-1L subform is synthesized in mouse lymphoid
      myeloma cells NS/0 of the B series and is not found in other somatic and
      embryonal cells. Initiation sites of oct-1R mRNA transcription are at positions 
      159 and -307 from the AUG codon of the oct-1R exon. In both cases, no TATA box
      was found in the region preceding these sites (25-30 bp). A different form of oct
      1 mRNA (oct-1U) was also found in NS/0 cells, which is probably synthesized in
      all cell lines. This subform differs from oct-1R, in particular, by the structure
      of the 5T-terminal exon, which is the result of alternative splicing.

PMID- 11234382
TI  - [DNA-(N4-cytosine)-methyltransferase from Bacillus amyloliquefaciens: kinetic and
      substrate binding properties].
AB  - Interaction of DNA-(N4-cytosine)-methyltransferase from the Bacillus
      amyloliquefaciens (BamHI MTase, 49 kDa) with a 20-mer oligonucleotide duplex
      containing the palindrome recognition site GGATCC was studied by methods of
      steady-state and presteady-state kinetics of the methyl group transfer, gel
      retardation, and crosslinking of the enzyme subunits with glutaric aldehyde. In
      steady-state conditions, BamHI MTase displays a simple kinetic behavior toward a
      20-mer oligonucleotide substrate. A linear dependence was observed for the
      reaction rate on the enzyme concentration and a Michaelis dependence of the
      reaction rate on the concentration of both substrates: S-adenosyl-L-methionine
      (SAM), the methyl group donor, and DNA, the methyl group acceptor. In independent
      experiments, the concentration of the 20-mer duplex or SAM was changed, the
      enzyme concentration being substantially lower then the concentrations of
      substrates. The kcat values determined in these conditions are in good agreement
      with one another and approximately equal to 0.05 s-1. The Km values for the
      duplex and SAM are 0.35 and 1.6 microM, respectively. An analysis of single
      turnover kinetics (at limiting concentration of the 20-mer oligonucleotide
      duplex) revealed the following characteristics of the BamHI MTase-dependent
      methylation of DNA. The value of rate constant of the DNA methylation step at the
      enzyme saturating concentration is on average 0.085 s-1, which is only 1.6 times
      higher than the value determined in steady-state conditions. Only one of two
      target cytidine residues was methylated in the course of the enzyme single
      turnover, which coincides with the earlier data on EcoRI MTase. Regardless of the
      order of the enzyme preincubation with SAM and DNA, both curves for the single
      turnover methylation are comparable. These results are consistent with the model
      of the random order of the productive ternary enzyme-substrate complex formation.
      In contrast to the relatively simple kinetic behavior of BamHI MTase in the
      steady-state reaction are the data on the enzyme binding of DNA. In gel
      retardation experiments, there was no stoichiometrically simple complexes with
      the oligonucleotide duplex even at low enzyme concentrations. The molecular mass
      of the complexes was so high that they did not enter 12% PAG. In experiments on
      crosslinking of the BamHI MTase subunits, it was shown that the enzyme in a free
      state exists as a dimer. Introduction of substoichiometric amounts of DNA into
      the reaction mixture results in pronounced multimerization of the enzyme.
      However, addition of SAM in saturating concentration at an excess of the
      oligonucleotide duplex over BamHI MTase converts most of the enzyme into a
      monomeric state.

PMID- 11234383
TI  - [Elements of structural organization of the transcribed area of the ribosomal
      repeat (rDNA) in human peripheral blood lymphocytes].
AB  - The rDNA transcribed region (TR) was tested for accessibility to RsaI recognizing
      15 TR sites, DNase I, and photoinducible arylazide (N-(4-azido-2-hydroxybenzoyl)
      N,N'-diaminoheptane acetate) in isolated nuclei and, with arylazide, in intact
      cells. Arylazide entered cells well and did not appreciably affect the chromatin
      structure. Its photolysis products efficiently modified DNA in accessible sites.
      Single-strand breaks made by DNase I were not transformed in double-stranded in
      rDNA TR, suggesting the necessity of denaturing electrophoresis for such an
      analysis. About 70% of all rDNA copies proved poorly inaccessible to
      endonucleases and arylazide, the accessibility being higher in their 18S and 5.8S
      rRNA gene regions than in the regions of the external transcribed spacers (ETSs)
      and the 28S rRNA gene. Proteinase K disrupted this structure, and the
      corresponding copies were extracted from nuclei. This explained why in situ
      hybridization occasionally fails to reveal rDNA in the nucleolar fibrillar center
      (FC) on electron microscopic preparations. In other rDNA copies, TR (excluding 5'
      ETS) was accessible to nucleases and arylazide. These copies were not extracted
      from nuclei treated with proteinase K. Some of their RsaI sites were protected by
      tightly bound proteins. Seven such regions were identified in TR. Possible
      association of the molecular structure, nucleolar location, and functional state
      of rDNA is discussed.

PMID- 11234384
TI  - [Single turnover kinetics of phage T4 DNA-(N6-adenine)methyltransferase].
AB  - Interaction of T4 DNA-(N6-adenine)-methyltransferase [EC 2.1.1] was studied with
      a variety of synthetic oligonucleotide substrates containing the native
      recognition site GATC or its modified variants. The data obtained in the
      decisecond and second intervals of the reaction course allowed for the first time
      the substrate methylation rates to be compared with the parameters of the steady
      state reaction. It was established that the substrate reaction proceeds in two
      stages. Because it is shown that in steady-state conditions T4 MTase forms a
      dimeric structure, the following sequence of events is assumed. Upon collision of
      a T4 MTase monomer with an oligonucleotide duplex, an asymmetrical complex forms
      in which the enzyme randomly oriented relative to one of the strands of the
      specific recognition site catalyzes a fast transfer of the methyl group from S
      adenosylmethionine to the adenosine residue (k1 = 0.21 s-1). Simultaneously, a
      second T4 MTase subunit is added to the complex, providing for the continuation
      of the reaction. In the course of a second stage, which is by an order of
      magnitude slower (k2 = 0.023 s-1 for duplex with the native site), the dimeric T4
      MTase switches over to the second strand and the methylation of the second
      residue, target. The rate of the methyl group transfer from donor, S
      adenosylmethionine, to DNA is much higher than the overall rate of the T4 MTase
      catalyzed steady-state reaction, although this difference is considerably less
      than that shown for EcoRI Mtase. Substitutions of bases and deletions in the
      recognition site affect the substrate parameters in different fashions. When the
      GAT sequence is disrupted, the proportion of the initial productive enzyme
      substrate complexes is usually sharply reduced. The flipping of the adenosine
      residue, a target for the modification in the recognition site, revealed by
      fluorescence titration, upon interaction with the enzyme supports the existing
      notions about the involvement of such a DNA deformation in reactions catalyzed by
      various DNA-MTases.

PMID- 11234385
TI  - [Alleviation of type I restriction in Escherichia coli K12 in the presence of the
      arsR gene from pKW301 of Acidiphilium multivorum AIU 301].
AB  - A study was made of the antirestriction activity of Acidiphilium multivorum AIU
      301 ArsR, a repressor of the ars operon which confers resistance to arsenite and
      arsenate and is on pKW301. In Escherichia coli, arsR cloned under the control of
      Plac in a multi-copy vector alleviated restriction of nonmodified lambda DNA by a
      factor of 120, six times more efficiently than its analogs of conjugal plasmids
      R64 (incI1) and R773 (incFI). Amino acid sequence analysis showed that the three
      ArsR proteins have a homologous region of 38 residues, including the
      antirestriction motif, in their N domains, whereas the motif is in the C domain
      in the Ard proteins. The other regions are nonhomologous, and pKW301 ArsR is 33
      residues shorter than R64 and R773 ArsRs. The total charge is -4 in pKW301 ArsR
      and +2 in R64 and R733 ArsRs. A total negative charge was assumed to contribute
      to the antirestriction activity.

PMID- 11234386
TI  - [Effect of monovalent anions of various nature on conformation of DNA molecules
      in a water-salt solution].
AB  - Methods of intrinsic viscosity [eta] and beam flow birefringence were used to
      study the effects of some single-charged ions (F-, Cl-, Br-, J-, NO2-, NO3-, ClO4
      , SCN-, CH3COO-) on the size and thermodynamic rigidity of DNA molecule in
      aqueous solutions of sodium salts in a broad interval of ionic strength mu when
      temperature T is changed. It has been shown that the close interactions in a
      macromolecule and the resulting persistent length a of DNA are independent of the
      type of the salt anion over the whole interval of mu. On the contrary, specific
      volume of DNA molecule in solution, proportional to [eta] value, is quite
      sensitive to the anionic composition of a solvent which is due to the effect of
      anions and their hydration on the remote interactions in the macromolecule. The
      presence of polyatomic and halide anions is manifested differently in the [eta]
      value of DNA. Possible factors responsible for the observed effect and the role
      of structural alterations of water upon anion hydration are discussed.

PMID- 11234387
TI  - [Study of water-protein interaction by high resolution NMR].
AB  - The interaction between carbonic anhydrase B in the molten globule state and
      water molecules was studied by high-resolution NMR spectroscopy. NMR spin
      diffusion experiments revealed spin diffusion propagation from the protein to
      waters. This is a process of complex bioexponential kinetics presented in spin
      diffusion spectra as a change in water signal intensity dependent on the post
      excitation time of protein molecules. Its reverse, spin diffusion propagation
      from waters to the protein, was also found. These phenomena are protein
      concentration- and temperature-dependent and shown to be possibly explained with
      the assumption that there exist water-protein complexes provoking the formation
      of large branched associations. At a temperature above 309 K, a stepwise increase
      in the interaction between waters and proteins occurs in these complexes. The
      formation of water-protein associations is induced by increasing temperature
      and/or protein concentration. In these associations, at normal temperature, the
      protein mobility is close to that of carbonic anhydrase B dimers.

PMID- 11234388
TI  - [Molecular mechanisms of development and differentiation of eye structures in
      Drosophila and vertebrates].
AB  - The development of the eye is compared in Drosophila and vertebrates. Although
      the structure of the compound eye of invertebrates and of the cameral eye of
      vertebrates differs morphologically, there are striking similarities at the
      molecular level. Three groups of genes control morphogenesis of the eye: the
      genes responsible for eye rudiment formation, neurogenic genes, and proneural
      genes. In the eye rudiments of Drosophila and vertebrates, the homologous
      regulatory homeobox-containing genes ey/Pax6, so/Six3, rx/Rx, and optix/Optx2 are
      expressed. Transcription factors encoded by these conservative genes are involved
      in specific interactions with DNA. Another set of homologous genes, eya/Eya and
      dac/DACH/Dac, is also expressed during this developmental period. These genes
      encode nuclear transcription factors that are devoid of DNA-binding domains but
      are involved in the protein-protein interactions that control gene expression.
      Transcriptional complexes, which are products of homeobox-containing genes and
      nuclear factors, control morphogenesis of the eye in Drosophila and vertebrates.
      A similar set of homologous regulatory and nuclear genes controls morphogenesis
      during formation of ectopic eyes in Drosophila and vertebrates. Molecular biology
      approaches have allowed eye development to be examined at the level of
      developmental mechanisms. It has become evident that progress in understanding
      the mechanisms of eye development is due to studies carried out on Drosophila.
      Supporters of the idea of the polyphyletic origin of the compound and cameral
      eyes have noted significant differences in their structure and have failed to
      find distinct common features in their development. The hypothesis of the
      monophyletic origin of eyes has been substantiated by the results of molecular
      investigations.

PMID- 11234389
TI  - [Effect of cytomegalovirus on cell cycle progression and formation of
      pathological mitoses in cultured human diploid fibroblasts].
AB  - The effect of cytomegalovirus on the cell cycle was studied autoradiographically
      in an asynchronous culture of human diploid fibroblasts. The analysis of labeled
      mitosis showed that some cells infected in the S phase ceased to progress through
      the cell cycle at one of its phases (S, G2, or M); at the same time, at least
      part of infected cells remained capable of entering mitosis. Beginning from day 2
      after infection by cytomegalovirus, the accumulation of pathological mitotic
      cells blocked at metaphase was observed in the culture. Approximately 50% of
      these cells contained 3H-thymidine label above chromosomes. This fact suggested
      the possibility of pathological mitosis in cells that were infected both at the S
      and other phases of the cell cycle. The detailed morphological analysis of
      chromosomes at different stages of infection demonstrated that the degree of
      their morphological changes increases from slight (stronger condensation) to
      severe pathology (fragmentation). In the aggregate, the results of the study
      suggested that abnormal chromosome morphology resulted from irreversible cell
      division arrest under the effect of cytomegalovirus.

PMID- 11234390
TI  - [HOX genes in embryo- and phylogenesis].
AB  - This review is concerned with the structure and function of the protein products
      and homeobox genes of the HOX complex. We also trace a relationship between
      morphological evolution and the evolution of the homeotic complex.

PMID- 11234391
TI  - [The role of neuromediators and proteins in genetic and functional organization
      of animal brain].
AB  - It was shown that animals that differ in behavioral characteristics (August and
      Wistar rats) also differ in neurotransmitter and protein metabolism, which can be
      considered as tests that adequately reflect the functional condition of the
      central nervous system. These differences are expressed at the level of both
      subcortical structures (hippocampus and caudate nucleus) and various
      morphofunctional types of the sensorimotor cortex neurons (layers III and V).
      Studies on genetically different animals strains have revealed metabolic features
      that allow determination of individual behavioral features and estimation of
      individual brain structures in these processes.

PMID- 11234392
TI  - [Spermatozoa of the loach Misgurnus fossilis as a test system for identification
      of new centromere proteins].
AB  - We studied the possibility of using the spermatozoa of the loach Misgurnus
      fossilis L. for identification of centrosome proteins. It has been shown that the
      centrosome of the loach spermatozoa consists of a pair of centrioles of the
      standard structure and contains the marker protein gamma-tubulin, cytoplasmic
      microtubules branch out from it, and it does not contain any additional
      structures characteristic of the centrosomes of spermatozoa of many other fishes.
      A preparation enriched with intact centrosomes has been obtained from the loach
      spermatozoa. These centrosomes contained gamma-tubulin although they lost their
      ability to induce polymerization of microtubules. The preparation of loach
      centrosomes was successfully used to obtain a set of monoclonal antibodies
      against the mammalian centrosome. A new protein kinase LOSTEK was identified with
      the help of one of these monoclonal antibodies, SN2-3D2, which was localized in
      the centrosome and on then microtubules in both loach spermatozoa and cultured
      mammalian cells. Hence, the loach spermatozoa are a promising object for
      identification of new proteins of the mammalian centrosome.

PMID- 11234393
TI  - [Long-term effects of irradiation in the progeny of mammalian cells].
AB  - It is shown that gamma-irradiation has remote consequences for mammalian cells
      cultivated in vitro. Many generations in the progeny of cells surviving acute and
      chronic irradiation at high and low doses are characterized by a number of
      abnormalities, including delayed cell death, the formation of micronuclei and
      giant cells, an increased frequency of sister chromatid exchanges, a reduced
      potential for repair, the loss of adaptive response, and increased
      radiosensitivity. These phenomena are regarded as manifestations of genomic
      instability induced by ionizing radiation.

PMID- 11234394
TI  - [Evaluation of various methods of measurement of the microtubule length in the
      cytoplasm of cultured cells].
AB  - It is generally assumed that microtubules in tissue culture cells extend from the
      centrosome to cell periphery, and the length of individual microtubules averages
      several dozens of microns. However, direct electron-microscopic measurements have
      cast some doubt on this assumption. In this study, the average length of
      microtubules in cultured Vero cells was estimated using a combined approach. The
      length of free cytoplasmic and centrosomal microtubules was determined by means
      of electron microscopy in serial sections; concurrently, the length of free
      microtubules in the lamella was measured in preparations stained with tubulin
      antibodies (an indirect immunofluorescent method), by tracing saltatory particle
      movements along the microtubules in living cells. According to the data of
      immunofluorescent microscopy, microtubule length in the lamella averaged 4.57 +/-
      3.69 microns. However, since two or more microtubules can overlap, their length
      may be slightly overestimated by this method. On the other hand, saltatory
      movements are easy to monitor and measure fairly accurately, but their range may
      be shorter than the actual microtubule length because of a limited processiveness
      of motors (kinesin and dynein). On average, the trajectories of saltatory
      movements in living cells were 3.85 +/- 0.72 microns long. At the electron
      microscopic level, microtubule length was analyzed using pseudo-three-dimensional
      reconstructions of the microtubule systems around the centrosome and in the
      lamella. The length of free microtubules in the lamella reached 18 microns,
      averaging 3.33 +/- 2.43 microns; the average length of centrosomal microtubules
      was 1.49 +/- 0.82 microns. Good correspondence between the data on microtubule
      length and arrangement obtained by different methods allows the conclusion that
      most of free microtubules in Vero cells actually have a length of 2-5 microns;
      i.e., they are much shorter than the cell radius (about 25 microns). Microtubules
      extending from the centrosome are shorter still and do not reach the cell
      periphery. Thus, most microtubules in the lamella of Vero cells are free and
      their ordered arrangement is not associated with their attachment to the
      centrosome.

PMID- 11234395
TI  - [A protein inhibitor of polygalacturonase in apple fruits treated with
      aminoethoxyvinylglycine and cobalt chloride].
AB  - Ethylene evolution changes were monitored during storage of apple fruits (Malus
      domestica Borkh., winter variety Mantuanskoe) treated with
      aminoethoxyvinylglycine and CoCl2. The storage of fruits was shown to be
      accompanied by changes in the activity of a protein inhibitor of
      polygalacturonase (PIPG). This inhibitor has been previously isolated from apple
      fruit tissues. The protein inhibitor of polygalacturonase was also shown to
      inhibit the activity of an enzyme produced by certain nonpathogenic fungi. The
      role of PIPG in apple fruit resistance to these fungi is discussed.

PMID- 11234396
TI  - [Effect of melanins on lipid peroxidation].
AB  - Effects of melanins obtained from cultured Cladosporium cladosporidae fungi and
      Alpha grape on Fe(2+)-induced, Fe(2+)-ascorbate-induced, and NADPH-induced lipid
      peroxidation in rat liver, brain, and eye were studied. Melanins were shown to
      inhibit the accumulation of lipid peroxidation products in vitro. The inhibitory
      effects of melanins were not due to direct interactions of these pigments with
      superoxide anion (O2). However, melanins may interact with other free radicals.
      Melanins were demonstrated to have the ability to oxidize NADPH, which is
      probably one of the mechanisms of their antioxidant effects.

PMID- 11234397
TI  - [Microfungicid--a preparation based on trichoderma viride for plant diseases
      control].
AB  - A technology was designed for manufacturing a preparation based on Trichoderma
      viride Pers ex S.F. Gray that strongly suppresses the development of causative
      agents of certain plant diseases and displays a growth-stimulating activity.
      Cultivation of the strain in a liquid medium for 18-24 h produced up to 60 g dry
      biomass per liter nutrient medium. A marketable form created in this work
      conserves the activity of the mycelial preparation for six months. The
      preparation is compatible with insecticides (carbofos, vismetrin, talstar, and
      applaud) and certain fungicides (such as baitan). Tests performed with the liquid
      form of Mycofungicid (seeds were treated with this preparation at a dose of 20-30
      g per metric ton before sowing) showed its high efficiency in protecting cereal
      crops from plant pathogens. The incidence of plant diseases decreased by 65%, and
      crop yields increased by 15-20%.

PMID- 11234398
TI  - [Modulation of plant resistance to diseases by water-soluble chitosan].
AB  - Low-molecular-weight water-soluble chitosan with a molecular weight of 5 kDa
      obtained after enzymatic hydrolysis of native crab chitosan was shown to display
      an elicitor activity by inducing the local and systemic resistance of Solanumi
      tuberosum potato and Lycopesicon esculentum tomato to Phytophthora infestans and
      nematodes, respectively. Chitosan induced the accumulation of phytoalexins in
      tissues of host plants, decreased the total content and changed the composition
      of free sterols producing adverse effects on infesters, activated chitinases,
      beta-glucanases, and lipoxygenases, and stimulated the generation of reactive
      oxygen species. The activation of protective mechanisms in plant tissues
      inhibited the growth of taxonomically different pathogens (parasitic fungus
      Phytophthora infestans and root knot nematode Meloidogyne incognita).

PMID- 11234399
TI  - [Rapid assay for the assessment of a potential of chemical biocides to microbial
      destructors of industrial materials].
AB  - A colorimetric rapid assay for estimating the biocide potential of various
      chemicals towards metal biocorrosive and petroleum product degrading microbes was
      developed based on the reducing potential of live microbial cell. A water-soluble
      organic redox indicator, blue in the oxidized form and pink in the reduced form,
      was used as an indicator of the reducing potential of microbial cells. Once added
      to a suspension of vital microbial cells, it was reduced and changed in color. A
      good correlation between the results of this assay and viability control was
      obtained by employing surfactants and heavy metal ions.

PMID- 11234400
TI  - [ Fungal extracellular ribonucleases (Review)].
AB  - Results of studies of certain fungal extracellular ribonucleases mainly isolated
      from representatives of the genera Aspergillus and Penicillium are summarized.
      The isolation of these enzymes in highly purified states in the 1970-1980s
      strongly stimulated further studies of their structure, functions, and mechanisms
      of action. This also promoted the use of ribonucleases as catalysts in
      oligoribonucleotide syntheses and as objects of comparative and evolutionary
      biochemistry and other research works. Results of studies of the primary,
      secondary, and spatial structures of guanyl-specific fungal ribonucleases are
      reviewed. These studies revealed a high homology within the subfamilies of
      fungal, bacterial, and actinomycete RNases. Characteristics of the nonspecific
      Pb2 RNase are considered.

PMID- 11234401
TI  - [Nucleoprotein complexes of yeast and their biological effect on T-lymphocytes].
AB  - Complexes of nucleic acids and acid nuclear proteins that are active toward human
      T-lymphocytes were isolated from cells of bakers' yeast Saccharomyces cerevisiae.
      The conditions of isolation of nucleoprotein complexes by acid extraction
      followed by microfiltration for concentration of macromolecular components were
      optimized. Gel filtration and electrophoresis were used to study the composition
      and molecular weights of components of the preparations obtained. It was shown
      that nucleoprotein complex had a molecular weight of 1430 kDa. However, only one
      zone was determined by electrophoresis of the protein component with a molecular
      weight of 30 kDa.

PMID- 11234402
TI  - [Low-molecular-weight glycoprotein from cattle blood serum: structure and
      properties].
AB  - Amino acid composition, structure, and physicochemical properties of a low
      molecular-weight glycoprotein from cattle blood serum (SGP) were studied. The
      content of carbohydrates (represented by mannose-rich oligosaccharides) amounted
      to 45-50 wt %. The value of specific partial heat of SGP, measured by
      differential scanning calorimetry (DSC), equaled 1.8 J/g.K, which is
      characteristic of unfolded proteins. Circular dichroic (CD) spectra of SGP led us
      to conclude that it is not highly structured and that it occurs in the shape of a
      statistical globule. The protein was deglycated using anhydrous trifluoromethane
      sulfonate (TFMS), after which its amino acid composition and the sequence of a
      fragment were determined. The results indicate that SGP is a protein not studied
      previously.

PMID- 11234403
TI  - [Endonuclease from Proteus mirabilis].
AB  - Two isoforms of nuclease displaying DNase and RNase activities were found in the
      culture liquid and periplasm of Proteus mirabilis. The enzyme was isolated from
      the periplasm and then purified to a functionally homogeneous state. The nuclease
      was equally potent in cleaving denatured and native DNAs by the endonuclease
      mechanism and was designated Pm endonuclease. The endonuclease was shown to be a
      temperature-dependent enzyme with a pH optimum of 10.4-10.6, requiring the
      presence of bivalent metal ions and inhibited by citrate and
      ethylenediaminetetraacetate.

PMID- 11234404
TI  - [Beta-galactosidase of the superthermophilic anaerobic bacteria Thermoanaerobium
      sp. 2905 and its immobilization].
AB  - The composition of nutrition medium for cultivating the extreme thermophilic
      anaerobe Thermoanaerobium sp. 2905 was optimized, which enabled the bacterial
      beta-galactosidase production to be substantially enhanced. Xylan and ammonium
      phosphate were selected as optimal carbon and nitrogen sources, respectively. The
      enzyme was purified fivefold by precipitation of the aqueous cell extract with
      alcohol (1:1, v/v), and crude preparation with a specific activity of 46 U per mg
      protein was obtained. Cells of the extreme thermophile were entrapped into
      natural or synthetic latex.

PMID- 11234405
TI  - [Structure and functions of chaperones and chaperonins (Review)].
AB  - Folding and assembling of newly synthesized proteins is directed and effected by
      a group of relatively recently discovered proteins called molecular chaperones.
      These proteins not only control the assembling of native structures; they also
      remodel protein molecules that have wrong conformations. All molecular chaperones
      perform the same function, but structurally they are divided into groups of
      chaperones and chaperonins. These proteins are highly conserved in evolution and
      display an ATPase activity. Certain known chaperones and chaperonins are shown in
      the table, and their structures and mechanisms of action are described.

PMID- 11234406
TI  - [Coimobilization of superoxide dismutase, catalase and peroxidase].
AB  - For preparationing the polyenzyme antioxidant complex, containing superoxide
      dismutase (SOD), catalase and horseradish peroxidase (HRP), the different
      successivities of those enzymes co-immobilization were compared. The optimum
      successivity is provided by simultaneous co-immobilization of covalently bound
      HRP with the SOD and catalase. The catalytic enzyme activity and the catalase
      operational stability was kinetically characterized in various samples. For one
      sample, the influence of ascorbate, glutathione and ethanol on the catalase
      kinetic parameters was studied. A possible scheme of different processes at the
      H2O2 decomposition in the presence of co-immobilized SOD, catalase, HRP and the
      substrates-reductans was discussed.

PMID- 11234407
TI  - [Isolation and characteristics of immobilized aminoacylase from
      Streptoverticillium olivoreticuli].
AB  - Immobilization of aminoacylase from Streptoverticillium olivoreticuli by
      incorporation into acrylamide gel has been investigated. The data showed that the
      process should be carried out at constant pH. Thermal inactivation of the
      immobilized enzyme under the reaction conditions was studied. The kinetics of
      enzymatic stereospecific deacylation of N-acetyl-DL-phenylalanine was analyzed.
      The results of this study may be used in the synthesis of amino acid enantiomers.

PMID- 11234408
TI  - [Search for micromycetes--producers extracellular catalase and study of
      conditions of its synthesis].
AB  - Production of extracellular catalase by microscopic mycelial fungi (255 strains)
      belonging to different taxonomic groups was studied. Producers of extracellular
      catalase were found among fungi of the genera Penicillium, Talaromyces and
      Aspergillus. Strains of the genus Penicillium were the most active producers. The
      formation of catalase depended on the initial pH, carbon and nitrogen sources and
      their ratio, and the content of microelements in the medium. The yield of
      extracellular catalase produced by the strains selected (P. chrysogenum, P.
      funiculosum, P. pinophilum, and P. minioluteum) was not less than 400-1400 U per
      ml culture liquid.

PMID- 11234409
TI  - [The use of micromycetes for cleaning parts of aircraft].
AB  - The mycelial Fungi Penicillium funiculosum, P. citrinum, P. expansum, P.
      chrysogenum, Aspergillus ochraceus, A. alliaceus, A. luchaensis, A. flavus, and
      A. niger were isolated from enrichment cultures. These fungi actively destruct
      carbon deposits formed during exploitation of aircraft. A biotechnological method
      for removing fouling from parts of aircraft engines (PAE) was developed. This
      method is less laborious, more rapid and ecologically clean than contemporary
      chemical methods. Scanning microscopy was suggested to use for estimating the
      degree of decarbonization of PAE surfaces.

PMID- 11234410
TI  - [A new oil-oxidizing micromycete Fusarium sp].
AB  - The strain Fusarium sp. No. 56 isolated from natural oil-containing soil samples
      taken near the city of Oktyabr'skii, Republic of Bashkortostan, displayed a
      pronounced capability of biotransforming oil and its light and heavy fractions.
      This micromycete is nonpathogenic and can grow at 10 degrees C. The latter
      property is of practical significance for its uses in soil and water
      bioremediation under cold climatic conditions of Bashkortostan and other regions.

PMID- 11234411
TI  - [Strain of Pseudomonas aeruginosa--producer of bioPAV].
AB  - A Pseudomonas aeruginosa strain producing an extracellular surfactant
      (biosurfactant) was isolated. The growth of this strain, referred to as 50.3, on
      a mineral glycerol-containing medium produces an emulsifying activity (60%) and
      decreases the surface tension of the culture liquid by a factor of 2.8 (to 25
      mN/m). The optimum conditions for its growth and production of biosurfactants:
      intense aeration, pH 7.0-8.0, and the presence of Mg2+. The optimum biosurfactant
      properties were achieved when glucose was used as the only source of carbon and
      energy and NH4Cl was used as a source of nitrogen. The biosurfactant was isolated
      from the culture liquid by extraction and precipitation.

PMID- 11234413
TI  - [Comparative study of some parameters of energy metabolism in two strains of
      Saccharomyces cerevisiae].
AB  - A comparative study of energy metabolism in two strains Saccharomyces cerevisiae
      (the initial strain N 73 and laser-irradiated mutant strain Y-503) was performed.
      In all growth phases, the rates of oxygen consumption by cells of Y-503 were
      higher than in the initial strain. The maximum (threefold) increase in the rate
      of oxygen consumption was observed in the linear phase. The effects of
      respiratory chain inhibitors rotenone, antimycin A, and cyanide on cellular and
      mitochondrial respiration were identical. There are two sites of energy coupling
      in the respiratory chain of mitochondria in S. cerevisiae N 73 and Y-503, and
      electron flow mainly is mainly mediated by cytochrome oxidase. The data suggest
      that a higher respiratory activity of S. cerevisiae Y-503 cells in comparison
      with N 73 is associated with greater amounts of mitochondria and total surface
      area of coupling mitochondrial membranes, which appears to be a factor
      contributing to a high physiological and biochemical activity of this strain.

PMID- 11234412
TI  - [Use of celluloselytic nitrogen-fixing bacteria in the enrichment of roughage
      with protein].
AB  - A new strain of acid-tolerant facultative anaerobic cellulose-degrading bacteria
      Bacillus cytaseus 21 (Mc Bethe ef Scales, 1912), which are capable to fixing
      atmospheric nitrogen, was isolated. This strain is intended for solid-phase
      fermentation and enrichment with protein of cellulose-containing waste of plant
      cultivation.

PMID- 11234414
TI  - [Toxicity of mercaptoethanol to mutant strains of the yeast Pichia methanolica
      growing on different carbon sources].
AB  - Addition of beta-mercaptoethanol at a concentration of 2-3 mM to media containing
      methanol, glucose, or yeast extract caused a 50% inhibition of the growth of wild
      type yeast Pichia methanolica; mercaptoethanol at a concentration of 0.7 to 25 mM
      inhibited the growth of the mutant strain ecr1. The mutation mth1 of P.
      methanolica repressed its ability to consume methanol and was accompanied by the
      loss of alcohol oxidase (EC 1.1.3.13) activity. beta-Mercaptoethanol restored the
      ability of mth1 mutant cells to grow on methanol and stimulated their growth
      under derepression conditions. The growth effect of beta-mercaptoethanol during
      derepression was accompanied by partial restoration of alcohol oxidase activity.

PMID- 11234415
TI  - [Genetic factors in predisposition to bronchial asthma].
AB  - The ratio between the normal (+) and null (0) alleles of the genes encoding
      glutatione S-transferases M1 (GSTM1) and T1 (GSTT1) were studied in normal
      individuals from northwestern Russia (control group) and in patients with
      bronchial asthma (BA). The frequency of the GSTM1 0/0 genotype in the population
      sample was statistically significantly lower (37.8%) than in the BA patients
      (82.1%; chi 2 = 16.8; P < 0.001; w chi 2 = 15.7; alpha = 0.01). For the GSTT1
      gene, similar data were obtained. The frequency of the GSTT1 0/0 genotype in
      healthy donors was statistically significantly higher (16.3%) than in the BA
      patients (73.7%; chi 2 = 28.5; P < 0.001; w chi 2 = 23.22; alpha = 0.01). A
      significant preponderance of the compound homozygotes for the GSTM1 and GSTT1
      null alleles among the BA patients was observed. The frequency of the GSTM1 0/0,
      GSTT1 0/0 individuals among the patients was 57.9%, while it was only 4.7% among
      the controls (chi 2 = 27.4; P < 0.001).

PMID- 11234416
TI  - [Association between insertion-deletion polymorphism of the angiotensin
      converting enzyme gene and development of angiopathies in patients with non
      insulin dependent diabetes mellitus from the Chuvash Republic].
AB  - Insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene
      was analyzed in patients with non-insulin-dependent diabetes mellitus (NIDDM) and
      in the control group consisting of healthy subjects. The insertion allele (I) and
      genotype II were found to be associated with NIDDM. The frequencies of diabetic
      retinopathy and nephropathy in NIDDM patients were not associated with this
      polymorphism. However, an association was found between the DD genotype of the
      ACE gene and diabetic angiopathy in lower extremities.

PMID- 11234417
TI  - [A new pentanucleotide STR-marker, located in the intron of the ING1 tumor
      suppressor gene and its allelic polymorphism].
AB  - DNA samples of unrelated subjects from the Volga-Ural region of Russia were
      examined to study allele polymorphism of the pentanucleotide repeat (TTGTG)8
      localized to an intron of the tumor suppressor gene ING1. STR marker was
      registered in the EMBL database with the accession number AJ277387. In a sample
      of 119 individuals, three pentanucleotide alleles consisting of seven, eight, and
      nine repeated monomers were revealed. The allele frequencies were 0.24, 0.74, and
      0.02, respectively. Heterozygosity was 0.45. On the basis of these data, the
      repeat can be regarded as a polymorphic STR marker for the ING1 gene and used in
      population and clinical studies.

PMID- 11234418
TI  - [Evolutionarily-conserved gene CKAP2,located in region 13q14.3 of the human
      genome, is frequently rearranged in various tumors].
AB  - The human CKAP2 gene, which is involved in diffuse large B-cell lymphomas, was
      localized via screening the GeneBridge 4 somatic cell radiation hybrid panel by
      means of the polymerase chain reaction (PCR). The CKAP2 gene was mapped between
      the WI-15460 and WI-3673 markers at the boundary between regions 13q14.3 and
      13q21.1, at the distance of 14.39 cR (with 4.8 cR per cM) from the WI-5867
      framework marker (lod score > 2.26). The human CKAP2 gene displayed high homology
      to mouse and rat expressed orthologs, A CKAP2-like sequence was found in human
      chromosome 14 and assumed to be a pseudogene resulting from duplication and
      subsequent mutations of the CKAP2 gene on chromosome 13. A possible role of the
      CKAP2 gene in oncogenesis associated with deletions and rearrangements of region
      13q14.3-21.1 is discussed.

PMID- 11234419
TI  - [Genetic differences and similarities in the introduced population of European
      beaver (Castor fiber L., 1785) in the Kirov and Novosibirsk regions of Russia].
AB  - Potential factors were analyzed that affected the formation of gene pools of two
      introduced beaver populations founded in the 1940s-1950s by releasing beavers
      from Voronezh oblast and Belarus into rivers of the Kirov and Novosibirsk
      oblasts. The populations from these two regions were shown to differ in four
      allozyme loci (Ahd-2, Gpi, Es-5, and Dia-2). Within Kirov oblast, the samples
      from three tributaries of the Vyatka River differed in three other loci (Ck-1, Gp
      9, and Trf). It is suggested that these features of the allele distribution at
      these loci are explained by the history of the introduced populations,
      hybridization between beavers from Voronezh oblast and Belarus, and founder
      effect during the subsequent artificial and spontaneous migration. Generally,
      genetic differences between the populations in all studied loci were very small:
      D = 0.02 between populations from different regions and D = 0.01 between
      populations from the tributaries of third-order rivers of the Kirov oblast. At
      the same time, disequilibrium was detected for ten polymorphic loci in the
      combined sample from the populations of Kirov oblast, which indicates the
      existence of interpopulation heterogeneity at the level of local populations of
      fourth- and fifth-order rivers. The unexpected finding of a genetic similarity
      between one studied individual of Tuvinian beaver subspecies (Castor fiber
      tuvinicus) and C. f. orientoeuropeas was recorded.

PMID- 11234420
TI  - [Molecular characteristics of the new evolutionary-conserved nuclear protein
      e(y)2].
AB  - Molecular structural and function analyses of the Drosophila melanogaster
      enhancer of yellow 2 (e(y)2) gene showed that its product acts as a transcription
      factor and is one of the basic elements of the eukaryotic transcription system.
      The gene is expressed at all stages of D. melanogaster development and consists
      of a single intron coding for the protein of 101 amino acid residues. The e(y)2
      protein does not contain regions homologous to known proteins. The protein binds
      with chromatin but not with DNA. On evidence of immune staining, e(y)2 occurs in
      the nuclei of all D. melanogaster cells. Each nucleus contains approximately 1.2
      x 10(4) molecules of the protein. Immune staining revealed approximately 200
      sites of e(y)2 location on polytene chromosomes. The protein is evolutionarily
      conserved: its homologs were found in evolutionary distant organisms, such as
      plants, mammals, and protozoans. Amino acid sequences of human, rabbit, and mouse
      e(y)2 are identical to each other.

PMID- 11234421
TI  - [Nuclear protein e(y)2 from Drosophila melanogaster participates in transcription
      control].
AB  - Molecular analysis of a new evolutionarily conserved transcription factor, e(y)2,
      was carried out. The protein was detected in a complex of approximately 700 kDa
      contained in a Drosophila melanogaster transcription nuclear extract. The e(y)2
      protein was shown to interact with components of the preinitiation transcription
      complex TFIID. Addition of e(y)2 to a transcription extract of HeLa cells
      increased transcription 4-5 times when chromatin, but not free DNA, was used as a
      template. Genetic analysis showed that the C-terminal amino acid residues of
      transcription factor TAFII40 are important for its interaction with e(y)2.

PMID- 11234422
TI  - [Modeling dark puffs using P-transposons in Drosophila melanogaster polytene
      chromosomes].
AB  - Modeling of morphologically unusual "dark" puffs was conducted using Drosophila
      melanogaster strains transformed by construct P[ry; Prat:bw], in which gene brown
      is controlled by the promoter of the housekeeping gene Prat. In polytene
      chromosomes, insertions of this type were shown to form structures that are
      morphologically similar to small puffs. By contrast, the Broad-Complex (Br-C)
      locus, which normally produce a dark puff in the 2B region of the X chromosome,
      forms a typical light-colored puffs when transferred to the 99B region of
      chromosome 3R using P[hs-BRC-z1]. A comparison of transposon-induced puffs with
      those appearing during normal development indicates that these puff types are
      formed via two different mechanisms. One mechanism involves decompaction of
      weakly transcribed bands and is characteristic of small puffs. The other
      mechanism is associated with contacts between bands adjacent to the puffing zone,
      which leads to mixing of inactive condensed and actively transcribed decondensed
      material and forming of large dark puffs.

PMID- 11234423
TI  - [Identification of a gene, included in control of root system development in
      Arabidopsis thaliana].
AB  - Genetic and molecular genetic analysis of a lethal root mutant of Arabidopsis
      thaliana was carried out. The mutant was obtained from a collection created
      earlier by means of insertion mutagenesis. The mutation was found to be
      recessive. It was caused by an insertion of the T region of vector pLD3 used for
      transformation of germinating seeds when creating the collection of insertion
      mutants. A 118-bp DNA fragment flanking the left border of the insertion was
      isolated using the TAIL PCR technique, and its nucleotide sequence was
      determined. Computer analysis of this DNA region demonstrated that it was located
      in exon 32 of the YUP8HI2R.44 gene in chromosome 1.

PMID- 11234424
TI  - [Cytotoxic activity of melittin expressed by recombinant vectors in Acholeplasma
      laidlawii and Mycoplasma hominis cells].
AB  - Recombinant plasmids containing the mellitin gene under the control of the lac
      and the tetM gene promoters were used for studying cytotoxic activity of mellitin
      in cells of mollicutes (mycoplasmas) and Escherichia coli. After transformation
      of Acholeplasma laidlawii and Mycoplasma hominis cells with recombinant plasmid
      DNAs by electroporation, cell growth was suppressed. The expression of the
      mellitin gene in A. laidlawii and M. hominis cells was demonstrated using the
      reverse transcription polymerase chain reaction (RT-PCR). The possibility of
      using the mellitin gene in the recombinant vector as a potential antimycoplasmic
      gene-therapeutic agent with its selective expression in target cells is
      discussed.

PMID- 11234425
TI  - [Genomic imprinting in mammals].
AB  - A review of the data on the mechanisms and effects of genomic imprinting, an
      epigenetic phenomenon regulating the development in placentate mammals, is
      presented. In contrast to the majority of gene loci with biallelic expression,
      the expression of imprinted loci is monoallelic. In humans and mice, more than
      300 imprinted loci have been identified, in which maternal or paternal alleles
      may either be expressed or be found in a repressed state during ontogeny.
      Imprinting is established during gametogenesis, and the repression of an allele
      of the imprinted locus is determined by methylation of the key regulatory element
      of this allele. Both the maternal and paternal chromosome sets are required for
      normal development in mammals. This is why parthenogenesis and androgenesis in
      these animals are impossible in nature. As a result of differential gene
      expression of many imprinted loci, the balance of gene activity is established,
      which is necessary for normal proliferation and differentiation of various cell
      clones in embryogenesis. Many human developmental abnormalities and syndromes are
      determined by defective genomic imprinting. In particular, the loss of imprints,
      which is followed by the occurrence of biallelic expression of some imprinted
      loci, may cause malignant tumors.

PMID- 11234426
TI  - [Mechanism of transformation in Pichia methanolica yeast: transforming and
      nontransforming genes].
AB  - Two types of genes were found in the study of transformation in yeast Pichia
      methanolica: transforming (Trg) and nontransforming (Ntg) genes. Transforming
      genes (P-ADE7,4 and S-LEU2), as linear DNA molecules, can transform competent
      cells with high efficiency inversely proportional to the molecule size.
      Nontransforming genes (P-ADE5 and H-LEU2) transform P. methanolica cells at an
      extremely low rate even when they are combined with transforming genes. The
      analysis showed that linear DNA molecules with Trg and Ntg can be either
      rearranged and integrated in random sites of the recipient genome or form
      circular plasmids, which are capable of autonomous replication irrespective of
      the presence of specific replicative elements.

PMID- 11234427
TI  - [Stability in development and variability in morphological signs in a natural
      population of Drosophila melanogaster: seasonal dynamics in 1999].
AB  - Seasonal dynamics of developmental stability and variability of morphological
      traits was examined in a natural population of Drosophila melanogaster in order
      to compare these two parameters as indicators of temperature stress. Morphometric
      (thorax length and wing length) and meristic (number of sternopelural and orbital
      bristles) were studied. Variability was measured as the coefficient of variation.
      Stability of development was estimated as fluctuating asymmetry (FA) of bilateral
      traits. Thorax length and wing length did not exhibit consistent seasonal trends
      whereas wing loading significantly decreased. Significant seasonal changes in FA
      were not detected in any trait examined. Two traits showed reduced variation in
      autumn. The use of FA as an indicator of ecological stresses in insects is
      discussed on the basis of these results and the literature evidence.

PMID- 11234428
TI  - [Some regularities in the genetic control of the stress reaction in Drosophila].
AB  - The heat-shock response was studied in Drosophila virilis strains with normal and
      impaired neurohormonal stress reaction. Flies from the latter strain were shown
      to have the impaired heat-shock response. In this strain, transcription of the
      heat shock gene hsp83 is reduced and synthesis of all heat shock proteins is
      suppressed. The neurohormonal stress reaction (status of dopamine, octopamine,
      and juvenile hormone metabolic systems) was examined in D. melanogaster strains
      having normal and impaired heat-shock response. The impairment of this response
      did not prevent the development of the stress reaction: in flies of both strains,
      the stress exposure resulted in an increase in the dopamine content and in a
      decrease in the activity of tyrosine decarboxylase (the first enzyme of dopamine
      synthesis) and in the level of juvenile hormone degradation. However, stress
      reactivity in mutant individuals differed from that in flies that did not carry
      stress-related mutations.

PMID- 11234429
TI  - [Genetic control of chromosomal synapsis in Secale cereale L. rye meiosis: sy19
      gene, causing heterologous synapsis].
AB  - Analysis of manifestation and inheritance of a new mutation inducing irregular
      synapsis in rye showed that abnormal phenotype is determined by a recessive
      allele of the sy19 gene. In the homozygotes for this mutation, even at the light
      microscopic level, abnormal formation of bivalents is already observed at
      pachytene-diakinesis. At metaphase I, the univalent frequency varies from 0 to
      14; in a few cells, multivalent associations of chromosomes, which are not
      clearly oriented in the spindle, are detected. Electron microscopy of
      synaptonemal complexes revealed both homologous and heterologous synapsis in
      homozygotes for sy19, namely partial loss of the ability to stringent homology
      search. Analysis of joint inheritance of sy19 and asynaptic sy1 mutations showed
      that they are nonallelic, inherited independently, and interact by recessive
      epistasis. The phenotype of double sy1sy19 mutants indicates that the sy19 gene
      conditioning heterologous synapsis operates at meiosis later than the synaptic
      gene sy1. The epistatic group of mutations, sy9 > sy1 > sy19 and sy3, was
      determined.

PMID- 11234430
TI  - [RAPD-analysis of corn somaclones].
AB  - The genetic difference between maize line A188 and A188-derived somaclones was
      assessed via analysis of randomly amplified polymorphic DNA (RAPD). In total, 15
      out of 17 decanucleotide primers used each allowed amplification of 2-17
      fragments ranging 200-2000 bp. The RAPD patterns did not differ between
      individual plants of line A188, which demonstrated again its high genetic
      homogeneity. The difference between the initial line and the somaclones was high,
      ranging 64-74%. On evidence of the genetic divergence, the somaclones formed two
      clusters. The distribution of somaclones between these clusters was consistent
      with their origin.

PMID- 11234431
TI  - [The role of genotype, social stress, and season of the year in regulation of
      hormonal function of murine testis in vitro].
AB  - Micropopulations consisting of six male mice of different genotypes were studied
      (each of lines A/He, CBA/Lac, C57BL/6J, DD, YT, and PT was represented by one
      male). Interlinear differences in the level of social dominance and the effects
      of genotype, social hierarchy, and season on in vitro testosterone production by
      testes were examined under different incubation conditions. The testosterone
      production was estimated under control conditions and under stimulation with
      human chorionic gonadotropin (CG). Significant genetic differences in the initial
      and CG-stimulated testosterone production by testes incubated in vitro were
      found. By the control production, the genotypes fell into two groups: lines
      C57BL/6J, A/He, and CBA/Lac had low production of the hormone; lines YT, PT, and
      DD, high production. By responsiveness of gonads to CG, the genotypes fell into
      three groups: line CBA/Lac had low testosterone production by testes; lines
      C57BL/6J, A/He, YT, and DD, line PT, intermediate production; and line PT, high
      production. The obtained data indicate stability of genetic polymorphism for the
      responsiveness of testes to gonadotropins, because neither season nor the
      formation of social hierarchy could significantly change the interlinear
      differences. In line PT characterized by high hormonal activity of gonads in the
      control and under stimulation with gonadotropins, males became dominant in a
      significantly greater number of cases studied during the formation of hierarchy
      in micropopulations. The dynamics of both control production of a male sex
      hormone and responsiveness of testes to CG was established in vitro during the
      formation of social hierarchy; the effects of season on this dynamics were
      revealed. Specific characteristics of secretory activity of testes were detected
      in the control and under stimulation with gonadotropins, depending on incubation
      conditions. Seasonal and genotypic characteristics of the responsiveness of
      testes to CG were revealed under different incubation conditions. Genotypic
      characteristics indicate interlinear differences in the degree of inertia of
      testosterone biosynthesis on exposure to gonadotropins.

PMID- 11234432
TI  - [Neurotransplantation of the fetal tissue and compensatory-restorative processes
      in the recipient nervous system].
AB  - Last years the allogenic neurografting starts to be use in clinic for the
      treatment of some diseases connected with organic and functional disorders of
      CNS. This review is devoted to analysis of the literature data and the results of
      own investigations about the influence of the immature nervous tissue grafts of
      the different genesis on the compensatory-restorative processes in the central
      nervous system of mammalian recipients with different models of nervous diseases,
      mainly the brain traumas. Besides it, the physiological-active substances of
      developmental brain, the donor materials alternative to allogenic solid and
      suspensions grafts, the ways to prevent the xenogenic nervous tissue rejection
      without immune suppressive therapy were analyze. The conception about mechanisms
      of neurografts influence on the recipient brain was suggested.

PMID- 11234433
TI  - [Embryonic stem cells (from fundamental biology to medicine)].
AB  - The recent achievements in isolation, primary and long term culturing, cell
      Immunophenotyping, SAGE--mRNA--profiling, the clonogenic growth parameters of
      embryonic stem cells and mesenchymal stem cells have been outlined in connection
      with cell pluripotency and restricted differentiation, mediated by signals both
      in culture and in situ. Multidisciplinary data obtained by cell biologists,
      embryologists with recent functional genomic data give the new way for practical
      implementation of bioimplants derived from embryonic stem cell for cell
      replacement therapy.

PMID- 11234434
TI  - [Embryonal nerve tissue transplantation--a tool for studying of early stages of
      the central nervous system development].
AB  - Human brain must not be use for experiments. It is necessary to create new
      approaches for study of brain developing mechanisms under unfavorable conditions
      of external and internal environments. One of such approaches is our model of
      human tissue development study into xenografts. This paper is analytical review
      of literature and data of authors about study human tissue neurotransplants.

PMID- 11234435
TI  - [Activity of vasopressin neurons in the human supraoptic nucleus: estrogen
      inhibitory effect].
AB  - Activity of magnocellular vasopressin (VP) neurons in the human hypothalamus is
      sex- and age-dependent as judged from the size of the Golgi apparatus, neuronal
      size and VP mRNA levels. These parameters are significantly higher in young (< or
      = 50 years old) men than in young women and are markedly increased in
      postmenopausal women compared to premenopausal women. This data suggest an
      inhibitory effect of estrogens on metabolic activity of VP neurons in the human
      supraoptic nucleus (2SON), which is likely to be mediated via estrogen receptor
      (ER) beta. Estrogens were shown to mediate their inhibitory effect via ER beta.
      It is expressed to a much higher degree in the SON of young women than in other
      groups, whereas estrogen receptor alpha, that mediates stimulatory effects of
      estrogens, is present in a small proportion of SON neurons. In addition,
      estrogens inhibit p75 neurotrophin receptor expression in VP cells. In
      conclusion, we discuss the inhibitory role of estrogens in functional activity of
      human VP neurons, which is most probably mediated directly via ER beta and
      indirectly by p75 neurotrophin receptor.

PMID- 11234436
TI  - [Cellular and molecular mechanisms in focal epileptogenesis].
AB  - In the review, it is presented an analysis of experimental data about cellular
      and molecular mechanisms of focal epileptogenesis. Basic principals of
      synchronized burst activity development in epileptogenic focus are considered.
      The roles of synaptic activities and extrasynaptic membrane excitability for
      epileptiform activity development are discussed. The various pathways of Ca2+
      entry into neurones as well as an involvement of Ca2+/calmodulin-dependent
      protein phosphorylation in mechanisms of epileptogenesis are analyzed. In vitro
      and in vivo experimental models of epileptogenesis (especially, kindling and
      audiogenic seizures) allowing to study the predisposition of neuronal circuit to
      epileptiform activity development are discussed.

PMID- 11234437
TI  - [The role for the hippocampus in the biorhythmical behavior].
AB  - The hippocampus as a important limbic structure has polyfunction properties among
      which take place chronotropic activity. It is showed in instability of different
      biological rhythms that provided for adaptation of organism to changing
      environment conditions. Chronotropic activity may be depenede from reciprocal
      connections of the hippocampus with brain rhythmorganizing structures
      (suprachiasmatic nuclei of hypothalamus and pineal gland). Increase of
      hippocampal excitability after chronic stress are produce disorganization of some
      rhythmic processes and followed neurosis or psychical depression. Psychotropic
      drugs (anxiolytics and antidepressants) by means of intensified of hippocampal
      inhibitory mechanisms (previously GABA and 5-HT) are stabilized of biorhythms
      what determined their specific anxiolytic and antidepressant effects.

PMID- 11234438
TI  - [Functional characteristics of ganglion neurons of the lower respiratory system].
AB  - In article it was shown our and literature date, in which examine of structural
      and electrophysiological properties of trachea and bronchi intramural neurons
      plexus. The interaction between different neurons are studied. It was shown that
      on the basis functional properties a neurons of intramural ganglion are divided
      on oscillatory, sensory, tonic and effectoric exciteties and inhibitory
      activation of muscle cells. The neurons are united to functional models
      controlling work of airway wall smooth muscle.

PMID- 11234439
TI  - Perspectives. Disease management for Medicare: how many paradigms can we shift
      today?

PMID- 11234440
TI  - [Effects of one cycle of inhalation crenotherapy with radioactive fluoridated
      oligomineral].
AB  - The objective of the study was to test the effects of inhalation crenotherapy
      using the radioactive, fluoridated oligomineral waters from the Merano Spa on
      both subjects with specific upper respiratory tract phlogosis and normal
      subjects. The double-blind study was performed on a population of 27 adults of
      both sexes treated with radioactive-fluoridated water (group A) and 20 subjects,
      suffering from the same chronic catarrh pathology, selected with the same
      criteria but treated with inhalation of steam and an aerosol using drinking water
      from the municipal water supply (group C). In addition, a group of 13 subjects-
      which in terms of age and sex were statistically comparable to groups A and C but
      who did not show any signs of acute or chronic upper respiratory tract
      pathologies (group B) were also treated with the radioactive-fluoridated waters.
      All subjects included in the study underwent the following tests before and after
      the cycle of crenotherapy: Objective E.N.T. examination. Computerized Active
      Anterior Rhinomanometry. Detection of the ciliary mucous transport (CMT) time.
      Nasal cytology. Physical and immunochemical examination of the nasal mucous. The
      results of this study--seen in the trend in some parameters monitored both before
      and after the cycle of crenotherapy using Merano Spa water--clearly show that
      that the crenotherapy studied had an effect on aspecific chronic phlogosis of the
      upper respiratory tract. In fact, among other things, group A showed decreased
      nasal resistance, increased nasal respiratory flow, normalized mucociliary
      transport, decreased bacterial flora and an increased number of plasma cells in
      the rhinocytogram. In addition there was an increase in the following values in
      the nasal mucous: Albumin, non-secretory Immunoglobulin and the secretory portion
      of secretory Immunoglobulin A. None of these variations are seen in the results
      from the control group treated with municipal drinking water. After treatment
      with Merano spa water, the pathology-free subjects showed variations in the
      parameters in line with those found for group A. This biological reality can most
      likely be attributed to the favorable response of the respiratory mucosa,
      promoting anti-infection defenses.

PMID- 11234441
TI  - [Distortion product otoacoustic emission (DPOAEs) and newborn hearing screening:
      a feasibility and performance study].
AB  - In view of the great psychological effect deafness has on one's social life, the
      scientific community has long sought the best way to define the hearing function.
      The development of new technologies in this field has set "early intervention" as
      the primary target for screening. For this reason, within the contest of a
      program of audiological newborn hearing screening, the Authors have used data
      from a selected group of 1250 newborns to (a) compare the clinical feasibility
      and performance of three different DPOAE protocols and (b) establish the scoring
      criteria defining "pass" or "fail" responses. All subjects participating in this
      study were randomly selected and their normal hearing was verified by linear
      TEOAE recordings. The test was carried out, using an Otodynamics ILO92 Analyser
      version 5.60, on the second day of life or later (in case of extended recovery),
      during natural sleep and after feeding. The DPOAE recordings were elicited using
      asymmetric stimuli with L1 > L2 and a frequency-ratio of 1.22 following three
      different SPL protocols: 60-50 dB (PR1), 65-55 dB (PR2) and 75-65 dB (PR3). Five
      frequencies of the cubic distortion product (referring to f2) were tested with an
      ILO macro at 1.5 KHz, 2.0 KHz, 3.0 KHz, 4.0 KHz and 5.0 KHz. The statistical
      evaluation of differences in the signal-to-noise ratio (S/N) between the PR1 and
      PR2 protocols showed no significant differences. On the other hand significant
      differences were found between the PR3 and the PR2 S/N ratios, the former
      providing the best performance (higher values). The scoring criteria were defined
      by minimum free distribution tolerance intervals of the S/N ratios at the five
      tested frequencies. In conclusion this study confirms the feasibility of DPOAE
      recordings in a un iversal newborn hearing screening program and shows the
      appropriate pass-fail parameters to be used for this purpose. It should be noted
      that this approach enables acquisition of frequency-specific information which
      might further improve audiological diagnosis.

PMID- 11234442
TI  - [The importance of upper respiratory tract shape in the treatment of chronic
      rhonchopathy].
AB  - The aim of the present work has been to verify what role the shape of the upper
      respiratory tract plays in both the onset of Obstructive Sleep Apnea and those
      cases which do not respond to treatment. Fifty patients with 1st stage chronic
      rhoncopathy according to the Lugaresi classification, were examined, all of whom
      underwent uvulopalatopharygoplasty. Of these 32 also under went tonsillectomy and
      45 had followed a diet prior to surgery. At 6 months and 2 years after surgery an
      endoscopy was perform with a video recorder to compare the pre- and post
      operative anatomic configuration of the oropharynx. Both the patients and their
      partners were presented a questionnaire to evaluate the degree of satisfaction
      with the treatment. The average follow-up was 30 months. Diet proved effective,
      especially in the most severe cases of obesity, with an average Body Mass Index
      which dropped from 30.5 to 26 after 6 months, rising to 28 after 24 months. The
      IAH went from 46.0 +/- 15.4 (SD) to 15 +/- 13.3 at 6 months, and rose to 27.5 +/-
      14.3 (SD) at 2 years. The degree of satisfaction of both patient and partner was
      88% at 6 months and dropper to 63% after 2 years. Videoendoscopy using a flexible
      lens was performed to evaluate the diameter of the positive results with surgery
      while it was the anterior-posterior axis in 70% of those who had negative
      results. In this study, after surgery, the larger URT diameter was latero-lateral
      in 62% of the patients while preoperatively it was so in just 10%. The use of
      tonsillectomy associated with UPP proved necessary to modify the shape of the
      URT.

PMID- 11234443
TI  - [Validity of schintigraphy in the study of neurogenic dysphagia].
AB  - The purpose of the present study was to verify the validity and potential
      application of oropharyngealesophageal scintigraphy in the analysis of neurogenic
      dysphagia. Scintigraphy was used on 36 patients divided into 2 groups: Group 1
      (control) comprised 17 healthy volunteers; Group 2 included 19 patients suffering
      from various neurological and neuromuscular pathologies (myasthenia gravis,
      Parkinson's disease, polymyositis, stroke, paralysis of the last cranial nerves).
      In group 1 scintigraphy provided normal results both for mode of swallowing and
      transit, and for the values of the various parameters studied. On the other hand,
      scintigraphy showed that in group 2 all oral, pharyngeal and esophageal phases of
      swallowing were altered vs the controls with a statistically significant increase
      in the average values for the oral transit time (OTT) (1.45 sec., p = 0.0005),
      pharyngeal transit time (OTT) (3.23 sec., p = 0.044), esophageal transit time
      (ETT) e19.87 sec., p = 0.005) as well as in the corresponding bolus retention
      indexes ORU (12.95%, p = 0.0003), FIR (15.05%, p = 0.0003) and ERI (28.63%, p =
      0.002). Moreover, the quality and means of swallowing also proved altered while
      tracheobronchial aspiration was only seen in 6 of the 19 patients (maximum value:
      90%, average value; 7.66%) with a marked prevalence in the stroke subgroup (4/8).
      In light of these results and considering the low dose of radiation (0.00043 Gy),
      the lack of invasiveness and excellent tolerability, scintigraphy has confirmed
      its clinical validity in the functional, objective and quali-quantitative study
      of deglutition, even in patients suffering from neurogenic dysphagia.

PMID- 11234444
TI  - [Platysma myocutaneous flap in oral cavity reconstruction].
AB  - Repairing soft oral tissues which have been removed for oncological reasons is as
      dauting as it is important. Currently there are many, often sophisticated,
      methods available but any search for the best possible results must also cause
      the least patient trauma. The pedicled myocutaneous platysma flap is not new to
      oral cavity reconstruction although it is not very widespread. We have
      occasionally used this surgical anatomy, the cases are presented. This flap was
      performed in 10 cases and proved quite effective; there was no case of total
      failure as indicated by an orocutaneous fistula. Cutaneous necrosis, partial or
      total, was seen in 4 cases although it did healed by second intention. The other
      reconstructive methods are then discussed along with the indications and
      contraindications as well as some technical insight. One can conclude that the
      myocutaneous platysma flap is a relatively simple, highly versatile solution
      although reliability is not the best. The Authors conclude that it is advisable
      for the surgeon to include the myocutaneous platysma flap as part of his
      therapeutic arsenal.

PMID- 11234445
TI  - [Nuclear DNA content in squamous cell carcinoma of the tongue: prognostic
      significance].
AB  - The prognosis is poor for advanced (stage III-IV) carcinomas of the tongue. The
      appearance of metastatic lymph nodes drastically reduces the 2-years survival
      rate because, in approximately 30% of the cases, metastatic lymph nodes are
      already present at the time of diagnosis, even in T1, but go undetected. The
      incidence of lymph nodes metastases has also been related to histological
      grading. However, this has not proved to be a reliable prognostic parameter, most
      likely because of the subjectivity of histopathological interpretation. Analysis
      of the DNA content, in association with other histopathological parameters, has
      proved to be a useful prognostic marker for other forms of tumors. This could
      also be the case for carcinomas of the tongue. The present study involved 26
      patients who came under observation at the Otorhinolaryngology Clinic of the
      University of Catania between January 1990 and February 1995. All patients were
      subject to biopsy sampling and subsequent treatment. According to the UICC
      classification, then slides were prepared and stained according to Feulgen. A
      computerized image analysis system (Image-ProPlus) was used to determine the
      quantity of tumoral nuclear DNA. Analysis of the nuclear DNA content showed that
      7 of the 26 carcinomas of the tongue (26.9%) were diploid, 19 (73.1%) aneuploid
      and of these 7 were also polypoid. In the aneuploid carcinomas the average DI was
      1.50 with a range running from 0.70 to 3.1. The correlation of 3-year survival
      and the clinically studied DNA content showed that 6 of the 11 stage I-II
      patients were disease-free and had an average tumoral DNA index of 0.95. On the
      other hand, those cases which showed progression or local recurrences had an
      average tumoral DI of 1.25. In the group of stage III-IV patients 5 were disease
      free and showed an average tumoral DNA index of 1.03 while those showing
      recurrence or progression of the disease had an index of 1.94. The above results
      appear to confirm that the risk of progression or recurrence is strictly linked
      to an increase in the average DNA value.

PMID- 11234446
TI  - [Biphasic hypopharyngeal synovial sarcoma: ultrastructural, cytofluorometric and
      immunohistochemical study and brief review of the literature].
AB  - Synovial sarcomas account for 7-10% of all soft tissue malignancies and the rare
      head and neck region location accounts for an average 5% of them. A brief review
      of the data in the Literature has shown that not more than one hundred cases of
      cervical-facial synovial sarcoma have been reported. In the head and neck
      locations this form of tumor is significantly less aggressive, with a higher
      survival rate and a recurrence rate much lower than the 60-70% shown for other
      locations in the limbs. After a brief review of the Literature, Authors present a
      rare clinical case of hypopharyngeal synovial sarcoma which recently came under
      observation. Despite the accurate diagnostic procedure, after surgical removal of
      the tumor by CO2 laser microlaryngoscopy, diagnosis required the use of
      histological and ultrastructural techniques. CT and NMR of the neck using
      contrast medium showed that the structure of the neoformation was similar to that
      of the soft tissues, it was 3-4 cm in diameter, located in the hypopharynx and
      had an extensive surface in contact with the left glossoepiglottic groove. The
      lesion appeared to involve the free edge of the aryepiglottic fold, coming into
      contact with the free edge of the epiglottis; it could not be dissociated form
      the epiglottis and obliterated both the homolateral glossoepiglottic vallecula
      and the pyriform sinus. Structural analysis after radiography with a contrast
      medium showed a marked impregnation of the lesion, indicative of high degree of
      vascolarization. Ultrastructural, cytofluormetric and immunohistochemical
      analyses were performed on the neoplasm in order to process all these data
      together with the clinical parameters; in other words a multi-parameter
      evaluation was performed, as suggested by other Authors, to determine the therapy
      and arrange more accurate monitoring of this patient, victim of a neoplasm with a
      high potential for metastases.

PMID- 11234447
TI  - [Palatine tonsillar metastasis from small cell carcinoma of the lung].
AB  - With regard to the rarity of metastatic tumor of the oropharyngeal region, we
      report a case of tonsillar metastases from the small cell carcinoma of the lung
      with controlateral cervical lymphadenopathy. The review of literature and the our
      clinic experience confirms the opportunity for an exclusively palliative
      treatment as then one no survivors in such events.

PMID- 11234448
TI  - Kimura's disease: a report of three cases with a brief review of literature.
AB  - Kimura's disease (KD) is an uncommon chronic inflammatory condition of unknown
      aetiology involving subcutaneous tissue, presenting as a tumor like lesion with a
      predilection for the head and neck region. Clinically it is often confused with
      parotid tumor with lymph node metastasis. It is difficult to diagnose before
      tissue biopsy. Fine needle aspiration cytology has only limited value. Unless the
      pathologists are aware of this entity, it might be misdiagnosed. Surgery,
      radiotherapy and steroid therapy have been tried but none is proved best and
      recurrence is common. Three cases of KD seen in our hospital and the problems
      encountered in them are presented.

PMID- 11234449
TI  - [Quinine and aspirin: two parallel stories with many touching points].

PMID- 11234450
TI  - [New approaches in cardiac surgery for the therapy of congenital heart disease].
AB  - Recent developments in the field of pediatric cardiac surgery and pediatric
      cardiology have led to significant changes in the surgical approach to the
      various cardiac malformations. There is a clear trend towards surgical treatment
      at a younger age of the patient, towards complete correction of malformations
      instead of staged procedures with initial palliation and delayed correction.
      Perioperative cardioprotection has improved significantly as has postoperative
      management in specialized pediatric cardiac intensive care units. As a result of
      this, mortality and morbidity of pediatric cardiac surgery have been in steady
      decline, although complexity of cardiac surgery in even smaller children has
      increased. Preoperative diagnostic work-up of the cardiac malformation can
      nowadays be achieved in an always increasing number of patients without invasive
      cardiac catheterization and based exclusively on ultrasound findings alone. A new
      element comes from the possibilities of therapeutic cardiac catheterization,
      which now allows for a combined therapeutic approach using therapeutic catheter
      procedures either to perform preparatory interventions prior to surgery or to
      treat surgical complications in the postoperative course. Refinements in the use
      of surgical implants have led to new possibilities of correction of complex
      malformations early in life, especially with regard to the use of biological
      prosthesis for valvar or outflow tract replacement.

PMID- 11234451
TI  - [Organizational and medical aspects of transition of juveniles with congenital
      heart defects to adult cardiology care].
AB  - A growing, heterogeneous group of children with congenital heart disease is
      surviving into adulthood due to advances in medicine. These patients including
      those with simple and complex congenital heart disease and operated on during
      childhood are facing long-term complications. Superspecialist care and expertise
      are required during their life to deal with their unique problems the most common
      being ventricular failure, arrhythmias, valve and conduit longevity. Teenagers
      and adolescents disappear from both medical and parental care because of the lack
      of transition programs. Transition of care from pediatric to adult cardiologists
      must be organized in each country and must reflect regional history, regional
      politics and realities. Transition of care requires goodwill from parents,
      adolescents, pediatric and adult cardiologists. Transition clinics being held
      jointly by pediatric and adult cardiologists between the age of 16 and 18 years
      are essential to encourage the adolescents to take charge of their own life and
      health issues. Adequate information about their heart defect, their operations
      and their residual lesions may help them understand the implications for the
      future and improve their compliance. A transition program must include counseling
      on education, career, endocarditis prophylaxis, insurance and lifestyle issues
      such as sexuality and reproduction (including anticonception, pregnancy),
      cardiovascular risk factors and sports activities. Medical reports including
      operative reports and heart catheterization reports must be transferred to the
      adult cardiologists. In Switzerland, care of adults with congenital heart disease
      is based on three levels: 1) primary caregivers including general practiioners,
      internists and community cardiologists; 2) cardiologists with special commitment
      and expertise to patients with congenital heart disease who organize regional
      outpatient clinics; 3) supraregional referral centers with cardiologists trained
      in pediatric and adult congenital heart disease and experienced in the special
      needs, problems and management of this unique population. A close collaboration
      between pediatric and adult cardiologists participating jointly in the care of
      congenital heart disease patients is very important. An interdisciplinary team
      offers all non-invasive and invasive facilities for diagnostic and therapeutic
      procedures in a supraregional referral center. A close collaboration among all
      physicians is crucial for optimal care and management. Integration of adolescents
      with congenital heart disease into an adult medical system improves both
      compliance and quality of care and supports the patient's esteem because many
      medical aspects and lifestyle issues are completely different from those during
      childhood.

PMID- 11234452
TI  - [Indications for pediatric cardiology evaluation].
AB  - Heart disease in infants and children may often lead to rapid decompensation.
      Early recognition by the primary physician is essential, since modern medicine
      and surgery can cure many heart defects. Main clinical signs are cyanosis, heart
      failure and/or abnormal auscultatory findings. Cyanosis appears shortly after
      birth or in small infants. In the newborn, cyanosis due to heart disease must be
      differentiated from pulmonary problems, sepsis or persistent pulmonary
      hypertension. Heart failure occurs more often in non cyanotic heart defects,
      mainly with left to right shunts. The main symptoms and signs of heart failure in
      the infant are briefly discussed. Abnormal auscultatory findings, usually
      murmurs, are the most common reason for referral to the paediatric cardiologist.
      However, most murmurs are "innocent" or "functional"; clues to their recognition
      are given. The present short review should help the primary physician to
      recognize signs of heart defects in infants and children so as to proceed with
      timely referral to the specialist.

PMID- 11234453
TI  - [Fetal and genetic aspects of congenital heart disease].
AB  - Fetal cardiology includes the assessment of the fetal heart for congenital heart
      disease (CHD) and arrhythmias, the management of affected fetuses, including
      parental counselling for the therapeutic options, the planning of the delivery
      and the postnatal care. This requires a close collaboration between
      obstetricians, neonatologists and pediatric cardiologists. Because of restricted
      financial sources extensive fetal echocardiographic assessment is reserved for
      pregnancies with increased risk for CHD, which includes a family history of CHD,
      suspicion of a cardiac or extracardiac fetal abnormalities at obstetric routine
      ultrasonography, fetal arrhythmias and chromosomal anomalies. Since most CHD
      occur in pregnancies without increased risk an ultrasound screening of the fetal
      heart during routine pregnancy ultrasound is recommended. Most forms of CHD can
      potentially be detected in utero, especially the severe ones with considerable
      fetal and postnatal morbidity and mortality. The prenatal diagnosis of a major
      cardiac malformation requires further assessments for extracardiac and
      chromosomal disorders. The deliveries of patients with major cardiac anomalies in
      a tertiary obstetric center close to a pediatric cardiac facility allows optimal
      perinatal and postnatal management. This may be of crucial importance for cardiac
      malformations which are arterial duct dependent postnatally. Many CHD have
      genetic causes. Well established is the association of CHD and the trisomies 13,
      18 and 21, as well as the monosomy XO (Turner syndrome). During the last years
      more and more molecular genetic causes for CHD could be demonstrated. The most
      significant one is the microdeletion 22q11 syndrome (CATCH 22 syndrome), which is
      associated with different conotruncal anomalies. Also for various other
      congenital cardiac malformations and syndromes a genetic cause could be
      demonstrated. The search for genetic cofactors is important as it affects
      parental counselling and patient care.

PMID- 11234454
TI  - [Emergencies in pediatric cardiology].
AB  - Congenital heart defects, not recognized antenatally, may lead to emergency
      situation immediately after birth. Fast recognition of clinical symptoms and the
      use of correct diagnostic tools are life-saving under these circumstances.
      Principles of cardio-pulmonary resuscitation will be presented in this article as
      well as diagnosis and treatment of hypoxemic spells, pulmonary hypertensive
      crises and (usually postoperative) pericardial effusion.

PMID- 11234455
TI  - [Diagnosis and treatment of childhood cardiomyopathies].
AB  - Cardiomyopathies have either a primary (without associated anomalies) or a
      secondary origin. They are classified in three groups according to their anatomy
      and function: hypertrophic, dilated or restrictive. We review here the relevant
      diagnostic points of each type as well as their treatment. Restrictive
      cardiomyopathies, arrhythmogenic right ventricle, non compaction and Uhl's
      anomaly will not be dealt with in detail as they are very seldom in children.

PMID- 11234456
TI  - [Clinical presentation, diagnosis and management of inflammatory heart diseases
      in childhood].
AB  - Inflammatory disorders which may affect the heart muscle, the endocardium, the
      pericardium and/or the coronary arteries are rare, but potentially devastating
      diseases. As the incidence of rheumatic heart disease has decreased, children
      with congenital heart disease now constitute the primary patient population at
      risk of infective endocarditis. Streptococcus viridans and Staphylococcus aureus
      are still the most frequently observed organisms. The majority of children with
      infective endocarditis can be cured today, but good results depend on early
      diagnosis and accurate treatment. Myocarditis occurs when the heart muscle is
      involved in an inflammatory process. Causes are numerous, but most common in
      children are infections with cocksackie viruses. Approximately two-thirds of
      children with symptomatic acute myocarditis show complete recovery of impaired
      ventricular function, 10-20% progress of dilatative cardiomyopathy and about 10%
      die or require heart transplantation. Kawasaki disease is the most prevalent
      inflammatory coronary artery disease and the leading cause of acquired heart
      disease in children. The origin of this acute systemic vasculitis remains
      unknown. Visible coronary arterial abnormalities develop in approximately 20% of
      children with untreated Kawasaki syndrome. A single dose of gamma-globulin (2
      g/kg over 12 h) given within the first 10 days of onset of illness as early as
      possible, in addition to aspirin has been shown to reduce the duration of fever,
      which may reflect the severity of ongoing vasculitis, and to reduce the
      prevalence of coronary artery anomalies.

PMID- 11234457
TI  - [Diagnosis and treatment of common pediatric supraventricular tachycardias].
AB  - The incidence of paediatric supraventricular tachycardias is approximately 0.1
      0.4%. AV node and AV reentrant tachycardias represent the most common
      supraventricular tachycardias in children. Atrial ectopic tachycardias are the
      second most common group of pediatric arrhythmias with a predominance in younger
      children. All these arrhythmias may result in a significant morbidity and
      necessitate therapy. During the last decade the widespread use of newer
      antiarrhythmic agents and the invention of radiofrequency catheter ablation have
      revolutionized the treatment of supraventricular tachycardias in children. A
      thorough knowledge of these various treatments options is essential to achieve a
      safe and effective management of supraventricular tachycardias in children. This
      article focuses on diagnostic and therapeutic aspects of the most frequent
      supraventricular tachycardias.

PMID- 11234458
TI  - [Options for interventional heart catheterization in congenital heart disease].
AB  - Parallel to the rapid advances in the surgical options in treating congenital
      heart defects pioneering innovations in interventional cardiology could establish
      alternative treatment to surgery for these patients. On the one hand there is a
      trend to interventionally cure simple heart defects, but on the other hand
      interventional procedures can often only support surgical treatment. This review
      gives a limited overview over the recent possibilities and problems of the
      interventional cardiology and therefore focuses on balloon dilatation of
      congenital valve or vessel stenoses, on device closure of intracardiac defects
      and on the implantation of stents for the enlargement of elastic or long
      stenoses.

PMID- 11234459
TI  - Obesity: preventing and managing the global epidemic. Report of a WHO
      consultation.
AB  - Overweight and obesity represent a rapidly growing threat to the health of
      populations in an increasing number of countries. Indeed they are now so common
      that they are replacing more traditional problems such as undernutrition and
      infectious diseases as the most significant causes of ill-health. Obesity
      comorbidities include coronary heart disease, hypertension and stroke, certain
      types of cancer, non-insulin-dependent diabetes mellitus, gallbladder disease,
      dyslipidaemia, osteoarthritis and gout, and pulmonary diseases, including sleep
      apnoea. In addition, the obese suffer from social bias, prejudice and
      discrimination, on the part not only of the general public but also of health
      professionals, and this may make them reluctant to seek medical assistance. WHO
      therefore convened a Consultation on obesity to review current epidemiological
      information, contributing factors and associated consequences, and this report
      presents its conclusions and recommendations. In particular, the Consultation
      considered the system for classifying overweight and obesity based on the body
      mass index, and concluded that a coherent system is now available and should be
      adopted internationally. The Consultation also concluded that the fundamental
      causes of the obesity epidemic are sedentary lifestyles and high-fat energy-dense
      diets, both resulting from the profound changes taking place in society and the
      behavioural patterns of communities as a consequence of increased urbanization
      and industrialization and the disappearance of traditional lifestyles. A
      reduction in fat intake to around 20-25% of energy is necessary to minimize
      energy imbalance and weight gain in sedentary individuals. While there is strong
      evidence that certain genes have an influence on body mass and body fat, most do
      not qualify as necessary genes, i.e. genes that cause obesity whenever two copies
      of the defective allele are present; it is likely to be many years before the
      results of genetic research can be applied to the problem. Methods for the
      treatment of obesity are described, including dietary management, physical
      activity and exercise, and antiobesity drugs, with gastrointestinal surgery being
      reserved for extreme cases.

PMID- 11234460
TI  - [Mechanisms of action of hypolipidemic agents].
AB  - Three classes of hypolipidaemic drugs are used currently for the prevention of
      cardiovascular diseases. Resins, by binding bile acids, prevent the intestinal
      reabsorption of these acids. Subsequently, an increase in their synthesis appears
      to arise from intracellular cholesterol. The intracellular cholesterol
      concentration decreases and leads to an increase in the number of LDL receptors.
      The consequence is a decrease in plasma LDL-cholesterol level. Statins act by
      inhibiting HMGCoA reductase, a key enzyme which regulates intracellular
      cholesterol synthesis. Thus, the intracellular cholesterol level decreases and
      leads to an activation of SREBP2 (Sterol regulatory element-binding protein), a
      transcription factor which, by binding to the promoter of the LDL-receptor gene,
      activates its transcription and thus the numbers of LDL receptors. The final
      effect is a decrease in plasma LDL-cholesterol. Fibrates activate a transcription
      factor named PPAR alpha. This activation results in binding with RXR, another
      transcription factor. The PPAR alpha/RXR heterodimer binds to the promoter of
      specific genes increasing their transcription and thus the proteins coded by
      these genes. This mechanism accounts for the increase in lipolysis (modulation of
      apoCIII and lipoprotein lipase) and in HDL-cholesterol (modulation of apoAI and
      apoAII genes).

PMID- 11234462
TI  - [The precautionary principle and medicinal products].

PMID- 11234461
TI  - [Prevention of cardiovascular diseases in elderly subjects with
      hypercholesterolemia].
AB  - Cardiovascular diseases are frequent in elderly subjects and these patients also
      frequently present with hyperlipidaemia. Therapy must take current uncertainties
      into account and, in the absence of therapeutic studies carried out in the
      elderly, is typically based on a case-by-case approach. Raised cholesterol levels
      remain a significant risk factor for coronary heart disease (CHD) in the elderly.
      Although the relative risk of CHD tends to diminish with increasing age, this
      reduction is accompanied by an increase in absolute risk (i.e. the number of
      events) as the frequency of the illness increases markedly with age. The results
      of major outcome studies with 3-hydroxy-3-methylglutaryl coenzyme A reductase
      inhibitors (statins), when analysed according to patient age, indicate that the
      benefits of these agents are not merely confined to younger individuals. However,
      the elderly form a unique patient population: the proportion of women is greater
      and the profile of cardiovascular illnesses is characterized, among other things,
      by a greater incidence of cerebrovascular accidents. Moreover, the potential
      widespread treatment of hyperlipidaemia in the elderly has profound economic
      implications. Under these circumstances, the clinical practice recommendations
      depend upon a reasonable extrapolation of epidemiological and therapeutic data
      obtained from middle-aged men. At present, treatment is therefore aimed at
      patients with the most severe forms of hyperlipidaemia, generally in the
      secondary prevention setting, taking into account the patient's life expectancy.

PMID- 11234463
TI  - [Study of combined anticoagulant (fluindione)-aspirin therapy in patients with
      atrial fibrillation at high risk for thromboembolic complications. A randomized
      trial (FFAACS)].
AB  - BACKGROUND: A combination of low-dose aspirin (A) and anticoagulation (AC) may
      provide better protection against thromboembolic events compared with AC alone in
      high-risk patients with atrial fibrillation (AF). METHODS: We performed a
      multicentric placebo-controlled double blind-trial to test the preventive
      efficacy against thromboembolic events of the addition of aspirin (A) (100 mg) or
      placebo (P) to anticoagulant treatment in patients with high-risk atrial
      fibrillation. A total of 157 patients were included, with atrial fibrillation and
      previous thromboembolic event or older than 65 years with either a history of
      hypertension, a recent episode of heart failure or a left ventricular
      dysfunction. All patients received fluindione (F) and P or F and A, with an INR
      target between 2 and 2.6. The primary endpoint was a combined endpoint of stroke
      (ischaemic or haemorrhagic), myocardial infarction, systemic arterial emboli or
      vascular death. RESULTS: The study had to be stopped prematurely owing to a too
      low recruitment rate. During follow-up (0.84 years) 3 non-fatal thromboembolic
      events were recorded (1P, 2A) and 6 patients died (3P, 3A), none of them from a
      thromboembolic complication. However, 3 deaths were secondary to severe
      haemorrhagic complications (1P, 2A). Non-fatal haemorrhagic complications
      occurred more often in group A (n = 10, 13.1 pour cent) compared with group P (n
      = 1, 1.2 pour cent), p = 0.003. CONCLUSION: The FFAACS study was not able to show
      any therapeutic benefit from the addition of aspirin to anticoagulant in patients
      with high-risk AF. Such a combination increased the incidence rate of bleeding
      complications, which therefore greatly reduces its potential overall benefit.

PMID- 11234464
TI  - [Antibacterial activity of urine after administration of ofloxacin for 5 days].
AB  - The antibacterial activity of ofloxacin was evaluated in urine over a period of
      96 h after oral administration for 5 days of 200 mg twice a day in 12 healthy
      female volunteers. Bacteriostatic and bactericidal activity of urines were
      studied for five strains of enterobacterias recovered from urinary infections:
      two strains of Escherichia Coli Nal-S and Nal-R, two strains of Proteus mirabilis
      Nal-S and Nal-R, and one strain of Klebsiella pneumoniae Nal-S. Mean urinary
      concentrations of ofloxacin were very high during the first 12 h following last
      intake. They were still above 7 mg/l till the 48th hour and above 1.6 mg/l till
      the 72nd hour. Bactericidal activity of urine was present for 72 h in respect of
      four strains studied at that time; urine was not bactericidal as regards E. coli
      Nal-R. After 5 days of oral treatment with ofloxacin (200 mg b.i.d.), urine
      retains a bactericidal activity for at least 72 h against bacterial strains of
      urinary tract infections.

PMID- 11234465
TI  - [Delayed drug-induced hepatic injury. Evoking the role of amoxicillin-clavulinic
      acid combination].
AB  - Although infrequent, hepatitis associated with amoxicillin and clavulanic acid
      combination is probably underestimated. Except for cases with few symptoms, a
      time interval between stopping treatment and the first manifestations (jaundice
      in most cases), sometimes of several weeks, may hinder diagnosis. We report 9
      patients who exhibited this characteristic. The delay between stopping treatment
      and the onset of hepatitis varied from 13 days to 6 weeks after stopping the
      drug. Other causes of jaundice were excluded. Male sex, advancing age, or
      prolonged treatment (more than 10 days) may increase the risk. Complete recovery
      occurs within 1 to 4 months after discontinuation of treatment. The mechanism is
      unclear. Clinical and biological signs of hypersensitivity may suggest an
      immunoallergic reaction.

PMID- 11234466
TI  - [Accidental narcotic and buprenorphine poisoning in children notified at the
      Marseille Poison Center between 1993 and 1999].
AB  - To evaluate the frequency and severity of accidental poisoning in children by
      narcotics or buprenorphine, a retrospective study was carried out: 75 cases were
      collected by the Marseille Poison Centre between 1993 and 1999. Most of the
      patients were between 1 and 3 years old and the drugs involved were cannabis and,
      more recently, Subutex (buprenorphine). These two drugs were responsible for the
      most severe cases of poisoning, most of which occurred at home.

PMID- 11234467
TI  - [Accidental ingestion of paracetamol in the for of the pediatric syrup
      EFFERALGAN: case studies during the six months following the institution of the
      child-proof top].
AB  - During the 6 months following the child-proof top commercialisation for the
      paediatric syrup EFFERALGAN in France, 51 cases of accidental ingestion were
      collected by the Marseilles Poison Centre. For 21 pour cent of them, the alleged
      dose taken was greater than the toxic dose. For 2 cases only, the responsible
      bottle had a child-proof top and was open on the table. For all other cases, it
      was simple-opening bottles (old bottles still present in houses, or bottles
      without a special top but sold in order to get rid of stocks). This study proves
      that such a preventive measure (modification of the top of the syrup bottles) is
      only fully effective if additional measures are undertaken such as return of
      unsold stocks or the provision of information to pharmacists and physicians.

PMID- 11234468
TI  - [Etiopathogenic and diagnostic aspects of cholesterol embolism].

PMID- 11234469
TI  - [Zinc and chronic obstructive pulmonary disease].
AB  - BACKGROUND: To evaluate the zinc organic concentration in the chronic obstructive
      pulmonary disease (COPD) in relation to a control group. Also, to analyze if the
      serum zinc levels are related with zinc concentration in erythrocyte, nail and
      hair. PATIENTS AND METHODS: Forty patients of COPD have been studied, all males,
      average age 62 +/- 7 years and body mass index (BMI) of 27 +/- 4. Forty patients
      were included in the control group, with average age 57 +/- 9 years and BMI of 24
      +/- 5. The patients with concomitant disease or booth treatment that could
      increase the zinc excretion were excluded. In all patients clinical history and
      examination, hematology and biochemistry tests, hepatic and lipid parameters, and
      nail, plasma, hair and erythrocyte zinc levels by atomic absorption
      spectrophotometry were done. Variance analysis and Pearson test were done.
      RESULTS: Blood, intraerythrocyte and nail zinc were similar in healthy subjects
      and patients; however, the median concentration of zinc in hair was significantly
      lower in patients (156 +/- 46 micrograms/g versus control group (185 +/- 64
      micrograms/g) (p < 0.05). No differences were found between smokers and no
      smokers, and drinkers and no drinkers in relation with body concentration of
      zinc. CONCLUSION: The zinc concentration in hair can be a good method to evaluate
      the chronic deficiency in the human body. The COPD patients could be susceptible
      to develop zinc deficiency; the situation increases the possibility of infection
      diseases.

PMID- 11234470
TI  - [Admissions estimate and inadequate stays in a regional hospital].
AB  - An inappropriate hospital use, defined as hospital utilization that could have
      been occurred at a lower attending level or in less time, increases costs,
      creates inefficient management and influences on attending quality. The objective
      of this work was to evaluate the appropriateness and inappropriateness of
      hospital admissions and stays in a district hospital for acute patients as well
      as causes of such inappropriateness. MATERIAL AND METHODS: Retrospective,
      descriptive study based on the review of clinical records of patients who
      required hospital admission. A sample of 378 patients representative of
      hospitalization for a 18-month period was selected. As measurement instrument the
      AEP (Appropriateness Evaluation Protocol) was used. This simple method has proved
      to be of high validity and reliability for the identification of inappropriate
      hospital use. RESULTS: The percentage of inappropriate hospital admissions
      detected was 13.8%, whereas the inappropriateness of hospital stays was 33.9%. As
      for clinical departments, the higher percentage of inappropriateness corresponded
      to the Traumatology Department (43%). The causes accounting for the
      inappropriateness of admissions related to the "necessity of admission"; but at a
      lower level, "diagnostic tests and/or therapy can be made on an outpatient basis"
      and "premature admission". As for hospital stays, the most common causes were
      "not rapid discharge", "diagnostic tests pending" and/or "any diagnostic and/or
      therapeutic procedure can be performed on an outpatient basis". CONCLUSION: The
      inappropriateness degree of hospital admissions and stays is similar to that
      observed in other more complex hospitals in our country. The causes underlying
      this phenomenon are dependent upon physician's decisions and social and public
      health conditions of the Area.

PMID- 11234471
TI  - [Cholesterol embolism disease: study of 16 cases].
AB  - BACKGROUND: The cholesterol embolism syndrome is a multisystemic disease
      resulting from cholesterol crystal embolization to many organs including skin,
      kidney and CNS. Vascular procedures and anticoagulation have been identified as
      triggering factors. PATIENTS AND METHODS: Sixteen patients were prospectively
      reviewed diagnosed of cholesterol embolism syndrome from 1991 to 1998. RESULTS:
      The mean age was 68 years and all had at least two risk factors for
      atherosclerosis (hypertension, smoking, diabetes mellitus, hyperlipemia) as well
      as pre-existing symptomatic atherosclerotic disease. At least one precipitating
      factor was identified in 14 patients (heparin in 7, coumarins in 4 and vascular
      procedure in 7). In six patients two or more triggering factors coexisted.
      Clinically, 12 patients had livedo reticularis, 10 purpuric lesions, 12 purple
      toes and 4 painful ulcerations. As a result of progressive gangrene 4 patients
      required amputation of a portion of the lower extremity. The skin biopsy was
      diagnostic of cholesterol embolism syndrome in 10 cases and was highly suggestive
      in the remaining cases. Eleven patients developed renal failure but only five
      required subsequent dialysis. A cerebrovascular accident was reported in two
      patients and gastrointestinal bleeding occurred in another three patients. Four
      patients died but only two as a direct result of the disease. CONCLUSIONS: The
      diagnosis of cholesterol embolisms should be considered among elderly patients,
      with underlying atherosclerotic disease, who develop typical cutaneous
      manifestations, hypertension, and renal failure in association with precipitating
      factors. Given the serious implications of this syndrome, a heightened awareness
      and preventive measures in the population at risk are essential.

PMID- 11234472
TI  - [Headache treatment].

PMID- 11234473
TI  - [Indications for hormonal replacement treatment in the postmenopausal woman].

PMID- 11234474
TI  - [Use of new quinolones in respiratory infections].

PMID- 11234475
TI  - [Diagnostic criteria and differential diagnosis of thrombotic thrombocytopenic
      purpura].

PMID- 11234476
TI  - [Diabetic dyslipidemia: clinical significance and therapeutic attitude].

PMID- 11234477
TI  - [17-year-old woman with headache and progressive diminishing of visual acuity].

PMID- 11234479
TI  - [Subcutaneous emphysema in a young male with acute gastroenteritis].

PMID- 11234478
TI  - [Pulmonary infiltrate in renal transplantation patient].

PMID- 11234480
TI  - [Neurologic deficit secondary to shot wound in a hunting accident].

PMID- 11234481
TI  - [Fatal cerebral hemorrhage in a frame of severe thrombocytopenia associated with
      Brucella infection].

PMID- 11234482
TI  - [Abscess of soft parts secondary to sacroiliitis brucellar].

PMID- 11234483
TI  - [Polyneuropathy and vasculitis of small vessel with detection of p-ANCA
      myeloperoxidase identity].

PMID- 11234484
TI  - [Spondylodiscitis and Streptococcus bovis meningitis: a rare association].

PMID- 11234485
TI  - [Churg-Strauss syndrome of childhood onset].

PMID- 11234486
TI  - [Red ear syndrome: a new case].

PMID- 11234487
TI  - [Prevalence of cutaneous lesions in Freixo de Espada a Cinta].
AB  - Incidence or prevalence studies on cutaneous lesions in general populations are
      not available. The community observed by the authors (Freixo de Espada a Cinta,
      North-Eastern Portugal) is relatively closed. A pre-tested questionnaire for
      socio-demographic and clinical information was used and a physical observation
      was conducted in January and February 1994 by the Dermatology Team of Santo
      Antonio General Hospital, Oporto. The analysis was supported by independent tests
      (Pearson and Fisher chi 2, Student-t, Mann-Whitney and Kruskall-Wallis). The
      Spearman correlation coefficient was also used. The results indicated that 51.9%
      of 1000 subjects analysed were in phototype III. Concerning specific pathologies,
      the following percentages were observed: melanocytic nevi 81.2; hemangiomas 26.5;
      androgenetic alopecia 20.5; deshydrotic eczema 12.7; seborrheic keratosis 11;
      solar keratosis 9.6; acne vulgaris 9.5; seborrheic dermatitis 6.9; superficial
      mycosis 6.4; other dermatitis 5.5; vascular spiders 4.4; vulgar psoriasis 1.9;
      vulgar warts 1.5; pediculosis and scabiosis 1.2.; herpes simplex 0.9; impetigo
      0.7; tumours (neoplasias) 0.7; dysplastic nevi 0.6; urticaria 0.3. More than nine
      nevi were counted in 50% of the subjects observed. A difference was observed (p <
      0.05) concerning the presence of nevi, mycosis, hemangiomas, non-specific
      dermatitis, vascular spider and solar keratosis according to sex. The females had
      more nevi in number than males (Mann-Whitney, p = 0.03). According to age there
      was a difference concerning the presence of nevi, superficial mycosis,
      deshydrotic eczema, seborrheic dermatitis, acne, psoriasis, tumours, hemangiomas,
      non-specific dermatitis, vascular spider, solar keratosis (with linear
      augmentation by age) and seborrheic keratosis. Nevi increased with ageing (Rs =
      0.10 p < 0.001) and a greater number were observed in age groups 0-9 and 60 or
      more years. Acne was observed in 9.4% of the females and 9.7% of the males, 46.2%
      in the 15-29 year-old age group. This study indicated that the population had a
      mean of nine nevi. Psoriasis was similar to that mentioned in other studies:
      about 1% in the United States of America. Atopic dermatitis (5.5%) is below the
      values for the northern population (> = 15%), but above that indicated for the
      English and American population. Nevertheless, the values of the present study
      were higher than those in the latter populations, when children until seven years
      old were considered. The Freixo de Espada a Cinta population above 60 years had
      solar keratosis in 30.6%, a value three times higher than the previous decade
      (10.9%); reference values were not found. Contrary to the literature, an
      association was not established between phototype and solar keratosis. Cutaneous
      tumours were observed in 0.7% of the cases.

PMID- 11234488
TI  - [Hysterosalpingography in the diagnosis of pelvic endometriosis].
AB  - Endometriosis is a common cause of chronic pelvic pain. Laparoscopy is considered
      the gold standard for definitive diagnosis. This work aims to evaluate whether
      hysterosalpingography (14SG), a cheaper and more accessible examination, is worth
      while as a diagnostic tool in this pathology. Thirty patients submitted to
      laparoscopy for chronic pelvic pain where retrospectively studied. Three
      different observers evaluated their hysterosalpingographies. The imaging
      diagnoses were classified as suggestive or not suggestive of external pelvic
      endometriosis. With laparoscopy, 18 patients had endometriosis, 11 with mild
      lesions by Acosta classification. Compared to laparoscopy, HSG diagnosis, when
      made by at least two observers, revealed a sensitivity of 55.5%, a specificity of
      75%, a positive predictive value of 77%, and a negative predictive value of 53%.
      In the presence of clinical pathologic uterosacral--US ligaments and/or
      sterility, the specificity of HSG may be 100%, but the sensitivity falls below
      the 40%. We concluded that in a population with chronic pelvic pain, HSG is not a
      first choice diagnostic tool. This examination only permits the identification of
      1/3 of the patients with external endometriosis, being unable to exclude its
      presence. However, it may be useful in patients with infiltrative endometriosis
      of the US ligaments.

PMID- 11234489
TI  - [Factors of recurrence of intraepithelial lesions of the uterine cervix].
AB  - MATERIAL AND METHODS: A retrospective study (1994-1996) of 282 cases of
      intraepithelial lesions treated in the Gynecology Services of Coimbra University
      Hospitals and subsequent follow-up (9-45 months). The following parameters were
      evaluated as recurrence factors: the patient's age, lesion degree, associated HPV
      infection, treatment type, safety margin in the ablative treatments and interval
      free of illness. RESULTS: Of the 282 cases, 72.4% (N = 204) corresponded to HSIL
      and 27.6% (N = 78) to LSIL. The patients' mean was 36.3 +/- 9.1 [19-67] years.
      The most commonly used treatment types were the LLETZ (large loop excision of the
      transformation zone) (76.9%) followed by CO2 LASER vaporization (16%) and finally
      cold-knife conization (7.1%). The safety margins were determined in 184 cases
      and, on average, were of 3.2 +/- 2.4 [1-10] mm. Forty-four recurrences occurred
      (15.6%) of which 75% corresponded to HSIL lesions (N = 33) and 25% (N = 11) to
      LSIL. From the total number of recurrences the association to HPV infection was
      found in 24 of the cases (54.5%) and 75% of these (N = 19) corresponded to HSIL.
      The average age in the recurrence group was 38.2 +/- 8.7 [21-53] years and 35.9
      +/- 9.2 [19-67] years in the group without recurrences (p > 0.05). In the LSIL
      group treated with CO2 LASER (N = 32) the recurrence rate was 15.6% versus 13.3%
      in the group treated with LLETZ (N = 45). In the HSIL that were treated with CO2
      LASER vaporization (N = 13) the recurrence rate was 23%; in those treated with
      LLETZ (N = 172) there were 16.2% recurrences and in the group submitted to cold
      knife conization (N = 19) that rate was 10.5%. CONCLUSIONS: The total rate of
      recurrence was 15.6% with the greatest incidence of lesions associated to HPV (p
      > 0.05). Regarding the particular case of the HSIL, a great number of recurrences
      with the destructive treatments (CO2 LASER) was observed when compared to the
      ablative treatments (cold-knife conization or LLETZ).

PMID- 11234490
TI  - [Detection of antiplatelet antibodies. The first one hundred samples studied].
AB  - Two types of platelet alloantigens are considered: type I, which refers to
      platelet alloantigens shared by platelets and other cells; and type II, which
      comprises the platelet-specific alloantigens. The Human Platelet Alloantigens
      (HPA) System consists of five diallelic alloantigens and eleven low frequency
      antigens. According to serological antigen capture assays, immunochemical methods
      and studies of Molecular Genetics, the glycoproteins (GP) of platelet membrane
      that are most frequently associated with antibodies are GPIIb-IIIa, GPIb-IX and
      GPIa-IIa. It is possible to detect platelet antibodies using different laboratory
      methods. Our experience was restricted to a solid phase system. In this method we
      used the indirect technique for the screening of alloantibodies and the direct
      technique for the detection of autoantibodies. The procedure with chloroquine
      solution was performed in order to differentiate between the presence of HLA and
      non-HLA platelet specific antibodies. Our comments are based on results obtained
      in a hundred samples tested throughout a period of eleven months and we briefly
      review the clinical features related to the diagnosis of autoimmune and
      alloimmune thrombocytopenia, drug-induced thrombocytopenia and other different
      factors of platelet destruction. The concepts of transfusional practice applied
      to emergency situations, platelet refractoriness strategy and the comprehensive
      management of patients are approached in this work.

PMID- 11234491
TI  - [Analysis of mutations in the BRCA1 gene in patients with cancer of the breast
      and/or the ovary in Portugal].
AB  - Germline mutations in the BRCA1 gene confer an increased susceptibility to breast
      and ovarian cancer. Approximately 460 distinct mutations were founded scattered
      throughout the whole gene. However, several mutations were detected repeatedly in
      individuals of the same ethnic origin. There are no systematic studies concerning
      mutations in BRCA1 gene in Portugal. The aim of this study is to identify
      mutations inh this gene in patients with breast and/or ovarian cancer of
      Portuguese origin. Thirty-three cases of breast cancer and 3 of ovarian cancer
      were selected according to early age of onset and family history. Mutation
      screening of this gene was done by Protein Truncation Test (PTT) and Fragment
      analysis. Two de novo mutations were identified: 1) A frameshift mutation
      localised in exon 11 of BRCA1, was identify by the two techniques in an ovarian
      cancer case. Direct sequential revealed a deletion of 4 nucleotides
      (3444delAAAT); 2) An alteration in intron 18 (IVS 18 + 80delT) was observed in a
      breast cancer case. This is probably the first description of mutations in a
      series of patients with breast and/or cancer in the Portuguese population. The
      mutations identified in this study have not been previously described in other
      populations according to the Breast Cancer Information Core web site.

PMID- 11234492
TI  - [Immunoglobin subclasses and determination of specific antibodies. What role in
      the study of children with recurrent pneumonias?].
AB  - BACKGROUND: Recurrent pyogenic infections, including pneumonia, are known to
      occur in children with a defective immune system. Until recently, diagnosis was
      made by measuring major immunoglobulin isotypes and IgG subclasses. Recent
      reports show that in some cases all these measurements are normal, but that there
      is a defect in the production of specific protein or polysaccharide antibodies.
      OBJECTIVE: To study immune function in children with recurrent pneumonia to
      determine the most appropriate immunologic studies for the evaluation of
      recurrent infections in children. METHODS: Forty-three children (ages 2 to 12
      years; mean 5.3 years, 29 male) who were referred to our pulmonology clinic
      because of recurrent lower respiratory tract infections. Major causes of
      recurrent infections were excluded by clinical, radiological or laboratory
      studies. Immunologic studies included serum immunoglobulins, IgG subclasses, IgA
      subclasses, isohemagglutinins and antibody responsiveness to vaccination with
      tetanus, rubella, H. influenza b conjugate and pneumococcal polysaccharide.
      RESULTS: The majority of children had normal or elevated serum immunoglobulin and
      subclass levels. Three patients had low levels of IgG2 and IgA, alone or
      simultaneously. Eleven patients failed to respond to Hib or rubella vaccination
      and one failed to respond to pneumococcal immunisation. CONCLUSIONS: Our
      preliminary results seem to indicate that a high proportion of children with
      recurrent pneumonia have a demonstrable immunologic abnormality. There is no
      direct relationship between low levels of IgG subclass and the child's capacity
      to form antibodies to several antigens. Defects in antibody production are very
      specific and an extended panel is necessary. Examination of the antibody-forming
      capacity seems important in the initial evaluation of children with recurrent
      pneumonia.

PMID- 11234493
TI  - [deficiency of growth hormone in children. Re-evaluation after therapeutic
      completion].
AB  - OBJECTIVE: To assess GH secretion in young adults treated with GH replacement
      therapy in childhood. PATIENTS AND METHODS: From the 38 patients who concluded
      treatment with GH, we studied 20 (52.6%), 9 girls and 11 boys. Thirteen had
      Growth Hormone Deficiency (GHD)-65%, while 7 had Multiple Pituitary Hormone
      Deficiency (MPHD)-35%. The patients were retested within 6 months to 6 years
      after completing GH therapy. The mean age (+/- SD) at retesting was 18.1 +/- 2.6
      years for those with GHD and 20.8 +/- 2.8 for those with MPHD. At reassessment we
      performed two provocative tests: insulin tolerance test (ITT) and clonidine test.
      RESULTS: Seven of the 20 patients retested, retained GH deficiency. Of the 13
      patients with GHD, only one maintained the deficiency, while of the 7 patients
      with MPHD, 6 maintained the deficiency. CONCLUSION: Young adults with GH
      deficiency treated with this hormone should be retested in order to identify
      those who are truly GH insufficient adults and may benefit from replacement
      therapy.

PMID- 11234494
TI  - [Classic/amyopathic dermatomyositis].
AB  - Dermatomyositis (DM) is an inflammatory myopathy characterized by a typical
      cutaneous rash and proximal weakness. DM results from endothelium deposition of
      the complement membranolytic attack complex C5b-9, followed by inflammation. It
      is thus possible to have cases of DM with the typical rash, but with no
      associated myositis--amiopathic DM. DM represents a higher risk of association
      with malignancy and sometimes behaves as a paraneoplastic syndrome. As DM can be
      the alarm sign, once diagnosed, exclusion of malignancy should be done. In this
      article we also discuss the treatment and prognosis of dermatomyositis, according
      to the literature.

PMID- 11234495
TI  - [A program of oral health for Portuguese youth. 10 proposals].
AB  - After a brief analysis of the current situation, based on transversal
      epidemiological studies on oral diseases, namely malocclusion, periodontal
      diseases and caries, accomplished by the author, a proposal for the organisation
      of the prevention and treatment phase of oral diseases in youngsters is
      presented. This proposal is aimed at obtaining the maximum effect with the
      simplest possible methods. It is centred on oral hygiene and the topical
      application of fluoride dentifrice and can be applied in every place by all
      youngsters. These are the essential bases for the prevention of periodontal
      diseases, in addition to caries. The early acquisition of the oral hygiene habits
      is essential for their important persistence along life.

PMID- 11234496
TI  - [Quality of health care].
AB  - Quality assurance is a relatively recent concern but already plays a major role
      in health care management and provision. Quality involves the definition of a
      comprehensive programme tailored by realistic and effective objectives and norms
      that include the structured review of procedures (namely clinical audits) and the
      use of up-to-date protocols. The involvement and motivation of health
      professionals, together with an adequate internal and external communication
      strategy, play a key role in the planning and application of these programmes.
      The use of programmed assessment, based on a solid knowledge of current practice,
      should have practical implications, optimising procedures in order to improve the
      quality of care. This commitment towards quality in health care should go far
      beyond governmental policy and should have clear support from health
      professionals.

PMID- 11234497
TI  - [Acute megaloblastic anemia caused by inhalation of nitrous oxide in a patient
      with multiple autoimmune pathology].
AB  - Although megaloblastic anemias are generally regarded as chronic conditions of
      insidious appearance, a megaloblastic state can arise over the course of only a
      few days due to acute folate or vitamin B12 deficiency. One of the most common
      causes, though seldom reported, is the nitrous oxide (N02) action in tissue. In
      fact N02, a volatile substance commonly used in anaesthesia, destroys
      methylcobalamin, leading to the rapid development of a megaloblastic
      haematopoiesis. This phenomenon may occur in patients without previous vitamin
      B12 deficit, but is more frequent and severe when there is a pre-existent
      deficiency state. A case report is described of a patient with femoral fracture
      who developed acute anemia after surgery and a latent pernicious anemia was
      revealed upon investigation.

PMID- 11234498
TI  - [Intestinal necrosis in children].
AB  - The term intestinal necrosis is nothing but a clinical and pathological concept
      and always includes intestinal ischemia, whether or not occlusive. In a broad
      sense, necrotizing enterocolitis involves intestinal ischemia associated to an
      infectious entity. The precipitating factor for necrosis is very often difficult
      to identify. Necrotizing enterocolitis occurs in 90% of cases in premature
      neonates and is less frequent amongst other neonates, being rare in older
      children and adults. The authors present two clinical cases: one 7 year-old with
      a history of chronic neutropenia and an eleven-year old with severe cognitive
      impairment, dysmorphic features and behavioural disturbances. They were both
      admitted to hospital due to an acute abdominal condition and shock. The necrosis
      implied the resection of a jejunal segment in one of the cases, and a subtotal
      colonic resection in the other. Despite the surgery and medical support therapy,
      they both died due to multiple system organ failure--3 hours and fourteen days
      after surgery, respectively. In the second case, death occurred subsequent to a
      second surgery for resection of a segment of necrotic ileum. Necropsy showed an
      extensive necrosis of the remaining intestine in both cases. These two cases
      evolved as necrotizing enterocolitis of the child. In one of the cases it was
      possible to establish the exclusion diagnosis of neutropenic enterocolitis. The
      etiopathogenic mechanisms are reviewed, including thrombotic, obstructive (both
      extrinsic and endoluminal), inflammatory, non-occlusive ischemic and infectious.
      The authors stress the general therapeutic measures, the relevance of early
      surgical intervention and the use of subsidiary diagnostic/therapeutic
      technologies, such as serum and urine title of intestinal fatty acid binding
      protein or selective arteriography.

PMID- 11234499
TI  - [Chronic diarrhea as late complication of partial gastrectomy].
AB  - The authors present a clinical case of a forty-nine-year-old man admitted to
      hospital because of a seven month history of diarrhoea. The patient had been
      submitted to partial gastrectomy twenty-two years ago due to peptic ulcer. The
      analytic study was compatible with malabsorption syndrome. The colonoscopic and
      radiological studies revealed the existence of two fistulas between the gastric
      stump, the small intestine and the colon. The patient was submitted to surgery
      with resection of the fistulas and re-gastrectomy with trunk vagotomy and Roux-en
      Y reanastomosis. The follow-up twelve months after surgery showed an asymptomatic
      subject with weight recovery who had resumed his professional activities without
      limitations.

PMID- 11234500
TI  - [Pleural effusion infected with Salmonella enteridis].
AB  - The authors describe the case of a 49 year-old caucasian male with left pleural
      effusion. The etiology of the effusion was exsudative with a preponderance of
      neutrophils. Ten days after admission and on empirical antibiotic therapy, the
      patient still had fever and the pleural effusion that became purulent. The
      thoracic echography and computerized tomography showed a subcapsular splenic
      abcess. The diagnosis was established by the culture of the pleural effusion and
      the isolation of Salmonella enteritidis enteritidis serotype. According to the
      antibiogram, a treatment with cotrimoxazole was established with clinical
      improvement. A splenectomy was performed.

PMID- 11234501
TI  - [Cavitated pulmonary condensation by Rhodococcus equi, in an HIV seropositive
      individual].
AB  - The first clinical case described in Portugal of a human infection by Rhodococcus
      equi in a 35 year-old HIV1 seropositive i.v. drug user is presented. The patient
      was admitted to hospital due to clinical and radiological suspicion of
      tuberculosis. While in hospital, a Rhodococcus equi cavitated lung infection was
      diagnosed. By applying a triple antibiotic therapy with erythromycin, rifampin
      and teicoplanin along with surgical excision of the lower lobe of the right lung,
      we were able to clinically resolve the pulmonary infection. A brief review of
      Rhodococcus equi infections, especially those associated to HIV1 infected
      individuals is also presented with particular emphasis on the therapeutic
      approach.

PMID- 11234502
TI  - [Hepatic amebiasis].
AB  - The authors report the case of a 30 year-old man, who had recently been to
      Africa, admitted due to fever and pain in the epigastrium and in the right
      hypocondrius. The evaluation led to the diagnosis of hepatic amebiasis. The
      patient was treated accordingly with success. The authors further review hepatic
      amebiasis, including the epidemiology, diagnostic means and ways of treatment,
      focusing on medical and surgical approaches and their controversies. The interest
      of the description of such a clinical case and the review that was made is
      derived from the current impact of globalization of the economy and its
      respective consequences due frequent trips to endemic countries. A detailed
      clinical history, including the epidemiology, is paramount for the suspicion of
      this diagnosis. Immediate treatment is mandatory, without which the patient may
      be at risk of serious complications.

PMID- 11234503
TI  - Plenty to sniff at. Smaller and more sensitive electronic noses open up new
      applications.

PMID- 11234504
TI  - Making sense of taste.

PMID- 11234505
TI  - Sculpting the earth from inside out.

PMID- 11234506
TI  - If humans were built to last.

PMID- 11234507
TI  - A sharper view of the stars.

PMID- 11234508
TI  - Evolution: a lizard's tale.

PMID- 11234509
TI  - The geography of poverty and wealth.

PMID- 11234510
TI  - The needy porcupine.

PMID- 11234511
TI  - [Oral contraception in puberty. Osteoporosis caused by the "pill"? (interview by
      Waldtraut Paukstadt)].

PMID- 11234512
TI  - [RR > 160/100 mmHg. Definitely an antihypertensive drug?].

PMID- 11234513
TI  - [No dyspnea but impaired performance. This could be asthma].

PMID- 11234514
TI  - [Separation anxiety, school anxiety, depression... Pediatric anxiety disorders
      have many faces].
AB  - Some 10-15% of primary schoolchildren and 5-10% of adolescents suffer from a
      pronounced anxiety disorder. This term is applied to a state in which the
      intensity and duration of the condition is out of all proportion to the "trigger
      situation". In the case of young children the most common disorder takes the form
      of separation anxiety and nocturnal restlessness. In schoolchildren, school
      phobia, a fear of going to school and playing truant with the associated fear of
      detection are distinguished. In children, anxiety is the soil on which depression
      may develop, is the dominant symptom in obsessive-compulsive neurosis and
      histrionic syndrome and is often masked by aggression. Treatment depends on
      severity, nature and duration of the disorder, as well as on the age of the
      child, and involves such aspects as parent counseling and treatment,
      psychotherapy and pharmacotherapy.

PMID- 11234515
TI  - [Child sexual abuse. How to deal with suspected abuse?].
AB  - Sexual abuse in children is defined as the exploitation of children by adults for
      the sexual gratification of the latter. A particular problem is sexual violence
      within the family. The chronicity of the abuse, by means of which the child is
      precipitated into role conflicts is typical. Whether inside or outside the
      family, sexual abuse almost always has negative effects on the child's
      development. When such abuse is suspected, a gentle physical examination and an
      empathetic age-adapted psychiatric diagnostic work-up are indicated. The
      overriding objective of an intervention is to protect the child. The indication
      of psychotherapy is determined by the severity of the symptomatology. Among other
      things, prevention strategies are aimed at increasing the autonomy of the child.

PMID- 11234516
TI  - [Attention and hyperactivity disorder in children. Early detection--preventing
      social consequences].
AB  - Attention deficit and activity disorder is characterized by impaired
      concentration, increased impulsiveness and motor restlessness. In a high
      percentage of cases, the symptoms persist into adulthood. Untreated victims have
      an increased risk of: failing to realize their full potential with regard to
      school-leaving performance, of developing substance dependence, of dissocial
      development, and of becoming more prone to accidents during leisure activity, in
      traffic and at work. The treatment strategies recommended in guidelines issued by
      the German societies of child and adolescent psychiatry are evidence-based and
      reliably effective.

PMID- 11234518
TI  - [Smoking cessation--fitness--vitamins. Health guidelines for rheumatic patients].

PMID- 11234517
TI  - [Autism in children. Speech, behavior and motor activity point to diagnosis].
AB  - Austistic disorders characteristically involve specific impairments of social
      skills, of the language and of stereotyped body movements. L Kanner and H.
      Asperger were the first to describe these psychopathologic features, which still
      form the core of the diagnostic criteria of contemporary psychiatric
      classification systems, ICD-10 and DSM-IV, in the category pervasive
      developmental disorders. Useful diagnostic tools have been developed to establish
      the clinical diagnosis. The results of research point to a predominantly genetic
      pathogenesis involving a complex interaction of multiple genes. While no causal
      treatments are available for these heterogenic disorders, there are many
      therapeutic concepts. Although some treatments may achieve significant
      improvements, autistic disorders usually mean a lifelong individual impairment.

PMID- 11234519
TI  - [Menstrual migraine. Diagnosis using a diary].

PMID- 11234520
TI  - [Screening study for detection insomnia in general practice. Diagnostic error in
      every second patient?].

PMID- 11234521
TI  - [A must in symptomatic heart failure. Added beta blocker improves prognosis].

PMID- 11234522
TI  - [An end to "doctor hopping" in sight? New therapy chances in irritable bowel
      syndrome].

PMID- 11234523
TI  - [Topical administration is better than oral administration].

PMID- 11234524
TI  - [New fixed combination for therapy of hypertension. "Softener" and "stimulant"
      supplement each other].

PMID- 11234525
TI  - [Orthopedic risk operation. Improved prevention of thromboembolism is in sight].

PMID- 11234526
TI  - [Report of experiences. Convenient limitation of blood glucose spikes].

PMID- 11234527
TI  - Spatial interpretation of ambient air quality for the territory of the Czech
      Republic.
AB  - A method for spatial interpretation and visualisation of measured air quality
      data is presented that may serve as a tool for ambient air quality
      characterisation using the least possible number of factors. This method enables
      comparison of different areas in relative terms and has practical consequences in
      decision making and public information. The 1996 data for the Czech Republic was
      used as a database. According to my results, not a single universal indicator can
      fully describe the ambient air quality albeit the three factors identified as
      "ambient air pollution", "ground-level ozone" and "wet atmospheric deposition"
      which are recommended. These selected factors represent three different aspects
      of ambient air quality and its impact on receptors. For the above factors black
      and white charts are presented classifying the Czech Republic territory into five
      categories as to relative ambient air quality. The air quality picture differs
      for the respective factors considerably.

PMID- 11234528
TI  - Ecophysiological responses of Empetrum nigrum to heavy metal pollution.
AB  - Chlorophyll, organic (citric and malic acids) and abscisic acid (ABA) contents
      and stem water potential were measured to indicate possible physiological effects
      of heavy metal deposition on Empetrum nigrum L. (crowberry). The leaves and stems
      of E. nigrum were collected at distances of 0.5 and 8 km from the Cu-Ni smelter
      at Harjavalta, south-west Finland. All the investigated parameters were clearly
      affected by heavy metal emissions. Chlorophyll contents in the leaves and organic
      acid contents in the leaves and stems were lower close to the emission source.
      Generally found increase in organic acid contents with increasing Ni
      concentrations was not found, which might be due to the lower production of
      organic acids measured by decreased photosynthesis near the smelter. In contrast,
      ABA contents in stems and leaves in general, were higher in plants growing 0.5 km
      from the pollution source. Close to the smelter the stem water potential of E.
      nigrum was less negative during the day but more negative during the night. These
      results suggest that smelter emissions have a negative effect on the
      ecophysiology of E. nigrum even though it is considered to be a tolerant species
      to heavy metals.

PMID- 11234529
TI  - Using benthic recruitment to assess the significance of contaminated sediments:
      the influence of taxonomic resolution.
AB  - The use of small-scale experimental units as a means of evaluating the ecological
      effects of contaminated sediments was examined at the species, family, mixed and
      phylum levels of taxonomic resolution. Sediments were taken from various
      locations representing a range of contaminant loads. Containers with these
      sediments were placed in situ at a relatively uncontaminated location for 90
      days. The containers were retrieved and the abundance of the macrofauna which
      recruited to the containers was estimated. The results showed that the
      composition of the benthic communities in the more highly contaminated sediments
      differed significantly from those in less contaminated sediments. Analyses at the
      different taxonomic levels showed that all but the phylum level data showed some
      differences in community structure among sediment types. The study showed that
      small-scale experiments are useful for examining the effects of contaminants and
      that higher levels of taxonomic resolution can be used to describe variations in
      the structure of benthic communities at this spatial scale.

PMID- 11234530
TI  - Organotins and imposex in the rock shell, Thais clavigera, from oyster
      mariculture areas in Taiwan.
AB  - The amounts of organotin compounds such as butyltins [sigma BTs: tributyl- (TBT),
      dibutyl- (DBT), monobutyl- (MBT)] and phenyltins [sigma PhTs: triphenyl- (TPhT),
      diphenyl- (DPhT) and monophenyl- (MPhT)] in rock shells, Thais clavigera, from
      the northern (Shiangsan), central (Lukang) and southern (Chiku) Taiwan oyster
      mariculture areas varied with season and location. High values of sigma BTs
      (mainly TBT) and low values of sigma PhTs (mainly TPhT) were found during winter
      (January 1999) at Shiangsan, while high amounts of sigma PhTs (mainly TPhT) and
      low sigma BTs (mainly TBT) were found during summer (August 1998) at Lukang. The
      snails were also affected by imposex. Imposex at Shiangsan, Lukang and Chiku
      increased from 67.1, 59.3 and 36.7% in summer to 100, 100 and 80% in winter,
      respectively. Relative penis size indices similar trend at Chiku site. No male
      displayed rock shells were found at Shiangsan and Lukang in winter. Linear
      correlations between pseudopenis length versus TBT (r = 0.7655, P < 0.001), DBT
      (r = 0.4253, P < 0.05), MBT (r = 0.5865, P < 0.01) and TPhT (r = -0.6160, P <
      0.01) were obtained significant. Among 200 samples, significant positive
      correlations between length (pseudopenis/shell) ratio of female versus TBT (r =
      0.6944, P < 0.005) and sigma BTs (r = 0.6413, r < 0.01) were also observed. The
      weak correlations between length (pseudopenis/shell) ratio of female versus DBT
      (r = 0.3085) and MBT (r = 0.4240, P < 0.1) and TPhT (-0.4917, P < 0.05; negative
      correlation) could indicate that DBT, MBT and TPhT have little or no effect on
      the development of imposex in rock shells.

PMID- 11234531
TI  - Exposure of migrant bald eagles to lead in prairie Canada.
AB  - The prevalence of elevated exposure to lead was assessed in a migrant population
      of bald eagles (Haliaeetus leucocephalus) at a waterfowl staging area in the
      southern portion of the Canadian prairies, from September to November, 1992-1995.
      Of 103 eagles, 8% exhibited blood lead (PbB) concentrations suggestive of
      elevated exposure to lead (> or = 0.200 microgram ml-1 wet wt.). PbB
      concentrations in eagles from the study area ranged from < 0.01 to 0.585
      microgram ml-1, while those of nestling eagles from a reference site indicated
      normal or background exposure (< 0.01 microgram ml-1). No differences in the
      prevalence of elevated exposure were detected among genders or age classes (0.5-
      and > or = 1.5-year-old birds) (P > 0.05). The prevalence of elevated exposure
      was significantly greater in November than in October (21.7 vs. 3.8%) (all years:
      chi 2Y = 5.75, P = 0.017). Eagles with shotshell pellets in the digestive tract
      did not have accompanying high PbB concentrations. The prevalence of elevated
      lead exposure in this study was low in comparison to other areas in North
      America. Potential biases in the trapping technique as they relate to
      interpreting the results are addressed.

PMID- 11234532
TI  - Relationship between epiphytic lichens, trace elements and gaseous atmospheric
      pollutants.
AB  - A study was conducted to determine the joint effect of gaseous atmospheric
      pollutants and trace elements on epiphytic lichens. We used our data to test the
      hypothesis that lichens are generally insensitive to toxic effects of trace
      elements, and can therefore be used as accumulator organisms to estimate
      concentrations of these elements in the environment. In a field study in The
      Netherlands the abundance of epiphytic lichen species was estimated, and their
      supporting bark was collected. Concentrations of a range of trace elements were
      determined in the bark, and concentrations of atmospheric trace gases were
      estimated at the sites of collection. Multivariate statistics were used to
      determine the relation between the abundance of the species and pollutant
      concentrations. Atmospheric SO2 and NO2 appeared to be the most important factors
      determining lichen biodiversity. Nearly all species were sensitive to these
      compounds. The effect of the other trace elements was very slight; only Sb had a
      significantly negative effect on the abundance of a few species. It is concluded
      that lichens can safely be used as accumulator organisms in pollution studies,
      provided that concentration in lichen thalli reflect atmospheric concentrations.

PMID- 11234533
TI  - Modelling the spatial distribution of SO2 and NOx emissions in Ireland.
AB  - The spatial distributions of sulphur dioxide (SO2) and nitrogen oxides (NOx)
      emissions are essential inputs to models of atmospheric transport and deposition.
      Information of this type is required for international negotiations on emission
      reduction through the critical load approach. High-resolution emission maps for
      the Republic of Ireland have been created using emission totals and a
      geographical information system, supported by surrogate statistics and landcover
      information. Data have been subsequently allocated to the EMEP 50 x 50-km grid,
      used in long-range transport models for the investigation of transboundary air
      pollution. Approximately two-thirds of SO2 emissions in Ireland emanate from two
      grid-squares. Over 50% of total SO2 emissions originate from one grid-square in
      the west of Ireland, where the largest point sources of SO2 are located.
      Approximately 15% of the total SO2 emissions originate from the grid-square
      containing Dublin. SO2 emission densities for the remaining areas are very low, <
      1 t km-2 year-1 for most grid-squares. NOx emissions show a very similar
      distribution pattern. However, NOx emissions are more evenly spread over the
      country, as about 40% of total NOx emissions originate from road transport.

PMID- 11234534
TI  - Relationships between ambient geochemistry, watershed land-use and trace metal
      concentrations in aquatic invertebrates living in stormwater treatment ponds.
AB  - Stormwater treatment ponds receive elevated levels of metals from urban runoff,
      but the effects of these pollutants on organisms residing in the ponds are
      unknown. We investigated the accumulation of Cu, Zn, and Pb by macroinvertebrates
      collected from stormwater treatment ponds in Maryland serving commercial,
      highway, residential and open-space watersheds, and determined whether watershed
      land-use classification influences metal concentrations in macroinvertebrates,
      sediments, and water. Three types of invertebrate samples were analyzed-
      molluscs, odonates, and composite. Zn concentrations in odonates from ponds
      draining watersheds with commercial development (mean = 113.82 micrograms g-1)
      were significantly higher than concentrations in the other land-use categories.
      Similarly, Cu levels in odonates from commercial ponds (mean = 27.12 micrograms g
      1) were significantly higher than from highway (mean = 20.23 micrograms g-1) and
      open space (mean = 17.79 micrograms g-1) ponds. However, metal concentrations in
      sediments and water did not differ significantly among land-uses. The results
      suggest that despite the high variation in ambient metal concentrations within
      each land-use category, macroinvertebrates in ponds serving commercial watersheds
      accumulate higher levels of Cu and Zn. The levels of Cu, Zn, and Pb in
      invertebrates from all ponds were less than dietary concentrations considered
      toxic to fish.

PMID- 11234535
TI  - Distribution of DDT residues in fish from the Songkhla Lake, Thailand.
AB  - Since the early 1950s DDT has been extensively used in Thailand as a malaria
      repellent and as an agricultural pesticide, but was finally banned in 1994. In
      this study concentrations of p,p'-DDT, p,p'-DDE, and p,p'-DDD in 113 fish of four
      species (Scatophagus argus, Protosus canius, Channa striata and Zonichthys
      nigrofasciata) are reported from the large, brackish Songkhla Lake and the Gulf
      of Thailand. The mean sigma DDT concentrations at different locations in the
      analysed fish species ranged from 33 to 170 ng/g lipid wt. (0.086-7.7 ng/g fresh
      wt.). This is well below the recommended maximum residue levels in aquatic
      animals used for human consumption (5000 ng/g fresh wt.) in Thailand. The
      comparatively low residue levels could be due to the high temperature and solar
      radiation in the region, which may result in a high volatilising and degradation
      rate of DDT. Also, the high productivity of the lake could result in a dilution
      effect, when DDT is distributed in a large amount of organic matter, followed by
      a high biological degradation of the substance.

PMID- 11234536
TI  - Differences in Cd elimination from Mytilus californianus and Mytilus trossulus
      soft tissues.
AB  - Field results have shown that Mytilus californianus is able to release its Cd
      concentrations significantly in just a few days. The existing paradigm states
      that Cd elimination from Mytilus soft tissues is a very slow process. This
      discrepancy was investigated in the laboratory, testing the effect of two Cd
      levels (10 and 1 microgram l-1) on its release from Mytilus trossulus and M.
      californianus soft tissues. After exposure to 10 micrograms l-1, both species
      showed a significant uptake with no elimination after several days of depuration.
      After exposure to 1 microgram l-1, the responses were different. No significant
      Cd uptake was seen in M. trossulus while in M. californianus uptake was
      significant but returned to the background level after just 1 day of depuration.
      This response of M. californianus is consistent with that reported from field
      studies. These results are important for environmental monitoring programs since
      M. californianus has been used as equivalent to other Mytilus species in the
      assessment of Cd pollution.

PMID- 11234537
TI  - Cadmium(II) removal from aqueous solutions by pre-treated biomass of marine alga
      Padina sp.
AB  - In this study, the adsorption properties of a pre-treated biomass from marine
      alga Padina sp., a biomass collected from Surin Island, Thailand, for removal of
      cadmium(II) ions from aqueous solutions was investigated. Batch and column
      experiments were conducted to determine the adsorption properties of the modified
      biomass. At a pH of 5, the maximum removal capacity of the biomass is 0.53
      mmol/g. The kinetics of cadmium(II) adsorption were fast with 90% of adsorption
      taking place within 35 min. This study demonstrated that the pre-treated biomass
      of Padina sp. could be used as an efficient biosorbent for the treatment of
      cadmium(II)-bearing wastewater streams.

PMID- 11234538
TI  - UV-absorbing compounds and waxes of Scots pine needles during a third growing
      season of supplemental UV-B.
AB  - Methanol-extractable UV-absorbing compounds, wax tube distribution and the
      chloroform-soluble waxes of the needles of mature Scots pines were studied in a
      UV-B field experiment in Oulu (65 degrees N). Throughout the experiment, UV-B
      lamp banks were placed over the same selected branch and each year needle samples
      were taken from the same branch. In the third exposure year, needle samples were
      taken twice a month from 3-day-old needles (18 June) to fully developed needles
      (13 August). On 28 September, the previous year's needles (c + 1, c + 2) were
      also collected. There was a significant negative correlation between the amount
      of waxes and UV-absorbing compounds. A high amount of UV-absorbing compounds was
      observed early and late in the season when the amount of waxes was low and
      epicuticular waxes were undeveloped (youngest needles) or already eroded (c + 2
      needles). The amount of UV-absorbing compounds (A310/cm2 and A320/cm2) was
      significantly (30-day-old needles) or slightly (all the other needle ages) higher
      in the ambient needles compared to the needles under supplemental UV-B. This
      possibly indicated the already inhibited pigment synthesis in the UV-B-treated
      needles during the third year of supplemental UV-B. This observation could mean
      that the protective mechanisms may not be effective under accumulated UV-B dose.

PMID- 11234539
TI  - Relevance of element content of bark for the distribution of epiphytic lichens in
      a montane spruce forest affected by forest dieback.
AB  - Element content in the bark on Norway spruce (Picea abies) was measured in a
      montane forest heavily affected by forest dieback and compared to that in a
      nearby intact stand. Bark contained less S, K, Fe, Mn, Pb, Cu, and H+ and more N,
      Ca, Mg, and Zn in the dieback-affected stand than in the intact one. Diversity of
      epiphytic lichen vegetation was higher in the dieback-affected stand than in the
      intact one. Cover of the foliose lichen Hypogymnia physodes was negatively
      correlated with Mn and Cu content of bark. Cover of the extremely acidophytic
      species Lecanora conizaeoides decreased with increasing Mg and increased with
      increasing Cu content of bark. The measurements support the hypothesis that
      chemical site factors are decisive for the high lichen diversity in dieback
      affected montane spruce forests.

PMID- 11234540
TI  - The environmental impact of shrimp aquaculture: a global perspective.
AB  - A global perspective on the environmental impacts related to the establishment
      and operation of shrimp aquaculture is presented. Alternatives to reduce the
      impacts are considered and research priorities are recommended.

PMID- 11234541
TI  - Effect of bone meal (calcium phosphate) amendments on metal release from
      contaminated soils--a leaching column study.
AB  - Metal-contaminated soil may be remediated in situ by the formation of highly
      insoluble metal phosphates if an appropriate phosphorus (P) source can be found.
      Leaching column experiments have been carried out to assess the suitability of
      bone meal as such a source. Bone meal additions reduced metal release from a
      contaminated soil, increased soil and leachate pH and decreased soil leachate
      toxicity. Minimal P leaching occurred from the soil. The data are consistent with
      a proton consuming bone meal (calcium phosphate) dissolution reaction followed by
      the formation of metal phosphates. Although, no metal phosphates were observed to
      form using X-ray diffraction of scanning electron microscopy this could be due to
      their low concentration. Relatively low (1:50 bone meal:soil) concentrations of
      fine (90-500 microns) bone meal would appear to be an effective treatment for
      metal-contaminated soils.

PMID- 11234542
TI  - Persistent organochlorine levels in six prey species of the gyrfalcon Falco
      rusticolus in Iceland.
AB  - Our previous investigations have revealed very high levels of organochlorines
      (OCs) in the Icelandic gyrfalcon Falco rusticolus, a resident top predator. We
      now examine six potential prey species of birds, both resident and migratory, in
      order to elucidate the most likely route of the OCs to the gyrfalcon. The
      ptarmigan Lagopus mutus, the most important prey of the gyrfalcon, contained very
      low levels of OCs. Bioaccumulation of polychlorinated biphenyls (PCBs) and DDTs
      in mallards Anas platyrhynchos, tufted ducks Aythya fuligula, golden plovers
      Pluvialis apricaria, purple sandpipers Calidris maritima, and black guillemots
      Cepphus grylle reflected their position in the foodchain. The differences in OC
      levels seem nevertheless too high just to reflect the different food-chain levels
      of these species in Iceland. The winter grounds of the migratory golden plovers
      and tufted ducks appear to be more contaminated than the Icelandic terrestrial
      habitat of ptarmigans or the freshwater habitat as reflected in mallards, both
      resident species. However, spending the winter on the coast in Iceland, results
      in high levels of contaminants in purple sandpipers and black guillemots. Our
      results indicate OC contamination of the marine ecosystem in Iceland while the
      terrestrial and freshwater ecosystems are little affected. It is postulated that
      gyrfalcons receive the major part of the observed contamination from prey other
      than ptarmigan, especially birds associated with the marine ecosystem and also
      from migratory birds.

PMID- 11234543
TI  - Simulation of 1-year-old Populus tremuloides response to ozone stress at Ithaca,
      USA, and Suwon, Republic of Korea.
AB  - The growth of 1-year-old aspen was simulated using TREGRO, a computer simulation
      model of individual tree growth, to assess potential effects of ozone (O3).
      TREGRO was parameterized using information from a field experiment conducted at
      Ithaca, NY, USA; the model was then applied using environmental information from
      Suwon, Korea, where O3 exposures of aspen had not been conducted. In the
      parameterization at Ithaca, the simulated and measured total biomass differed by
      about 3% and the differences between measured and simulated biomass gain of leaf,
      shoot, and root were 15.4, 8.3, and 4.4%, respectively. Simulating growth at
      Suwon required adjustment in growth rates to match measured growth due to the
      different weather conditions at the two cities. The assimilated carbon was evenly
      distributed to each tissue (foliage, branch, stem, coarse, fine roots) in Suwon,
      whereas it was mainly allocated to vigorous stem growth in Ithaca. The vigorous
      growth under Suwon conditions resulted in less total non-structural carbon and
      perhaps trees more vulnerable to O3 stress. Although the ambient O3 in Suwon (1.2
      ppm.h of sum of the hourly concentrations greater than 0.06 ppm [SUM06]) was
      lower than that in Ithaca (2.1 ppm.h of SUM06), a reduction of 8% of total
      assimilated carbon was found compared to simulation without O3. Severe effects on
      root growth at elevated O3 (1.7 times ambient) were predicted; however, the
      effects on leaf growth would not be as severe.

PMID- 11234545
TI  - Impact of composting strategies on the treatment of soils contaminated with
      organic pollutants.
AB  - Chemical pollution of the environment has become a major source of concern.
      Studies on degradation of organic compounds have shown that some microorganisms
      are extremely versatile at catabolizing recalcitrant molecules. By harnessing
      this catabolic potential, it is possible to bioremediate some chemically
      contaminated environmental systems. Composting matrices and composts are rich
      sources of xenobiotic-degrading microorganisms including bacteria, actinomycetes
      and lignolytic fungi, which can degrade pollutants to innocuous compounds such as
      carbon dioxide and water. These microorganisms can also biotransform pollutants
      into less toxic substances and/or lock up pollutants within the organic matrix,
      thereby reducing pollutant bioavailability. The success or failure of a
      composting/compost remediation strategy depends however on a number of factors,
      the most important of which are pollutant bioavailability and biodegradability.
      This review discusses the interactions of pollutants with soils; look critically
      at the clean up of soils contaminated with a variety of pollutants using various
      composting strategies and assess the feasibility of using composting technologies
      to bioremediate contaminated soil.

PMID- 11234544
TI  - The integrated use of chemical analysis, cytochrome P450 and stress proteins in
      mussels to assess pollution along the Galician coast (NW Spain).
AB  - Aliphatic and polycyclic aromatic hydrocarbons (PAHs) as well as biochemical
      markers, such as cytochrome P450, benzo(a)pyrene hydroxylase (BPH) and stress-70
      proteins, were determined in mussels (Mytilus galloprovincialis) collected in
      October 1995 from several locations along the Galician coast (NW Spain). The
      survey proved the existence of a pollution gradient among sampling sites and a
      chronic exposure to petrogenic and pyrolitic hydrocarbons. This was reflected in
      mussel tissue levels of PAHs which ranged from 22 to 562 ng/g wet weight. High
      levels of total cytochrome P450 were detected in mussels from the most polluted
      sites, but differences were not statistically significant. BPH activity did not
      show either differences among sampling sites. Conversely, stress-70 proteins were
      significantly induced in the most polluted locations, and levels of the 72-kDa
      band correlated well (r2 = 0.854) with the sum of the PAHs from four to six rings
      accumulated by mussels.

PMID- 11234546
TI  - What do sentinels stand for?
AB  - Sentinel species are biological monitors that accumulate a pollutant in their
      tissues without significant adverse effects. Primarily used to measure the amount
      of a pollutant that is biologically available, they may also increase the
      sensitivity of an analytical procedure or summarise a complex pollution signal.
      This paper examines the validation of sentinels, referring particularly to the
      use of invertebrates in monitoring toxic metal pollution in terrestrial
      ecosystems. Few studies measure the capacity of a sentinel to quantify changes in
      ambient levels. Definitions of 'bioavailability' also differ between workers and
      few note that this may be a highly species-specific measure. Validation requires
      that the temporal and spatial scales over which a sentinel integrates a pollution
      signal are known. The sentinel has to be calibrated against source concentrations
      and this relationship shown to be consistent over the normal range of exposure.
      This requires some consideration of the environmental and biological determinants
      of pollutant assimilation. Differences between populations can confound simple
      comparisons between sites based on native populations. Transplanted individuals,
      matched for age, sex and physiological state, might be used when the aim is not
      to assess bioavailability to the resident population. A simple measure of their
      capacity to detect differences in ambient pollutant levels is proposed to
      evaluate candidate species, to assess their consistency and capacity to
      equilibrate with their source. A small survey of earthworms from a well-defined
      gradient of Pb pollution is used to illustrate problems of interpreting tissue
      concentrations in sentinels.

PMID- 11234547
TI  - Enumeration and factors influencing the relative abundance of a denitrifier,
      Pseudomonas sp. JR12, entrapped in alginate beads.
AB  - The relative abundance of the denitrifier, Pseudomonas sp. JR12, was examined in
      an alginate-based entrapment complex under non-sterile, denitrifying conditions.
      Immuno-labeling of the Pseudomonas inoculant followed by flow cytometry (FCM) was
      used for determination of the relative abundance of this bacterium under the
      various incubation conditions. Additional information on the relative abundance
      of the inoculant was obtained by a quantitative enzyme-linked immunosorbent assay
      (ELISA) and results obtained by FCM and ELISA were compared. Ambient nitrate
      levels controlled the successful, long-term proliferation of the inoculant. At
      low ambient nitrate levels, Pseudomonas sp. remained the dominant microorganism
      during incubation. Higher ambient nitrate concentrations, attained by either
      decreasing the inoculum size of Pseudomonas sp. or raising inlet nitrate
      concentrations of the medium supplied to the incubation vessels, resulted in a
      gradual shift toward other, nitrite-accumulating denitrifiers. Thus far, most
      studies on the use of entrapped microorganisms for bioremediation purposes have
      been conducted under controlled laboratory conditions. Based on this study,
      conducted under non-sterile laboratory conditions, it is concluded that in-situ
      bioremediation using entrapped target microorganisms is bound to fail without a
      proper understanding of the factors that cause the target microorganism to out
      compete undesired microbial invaders. Furthermore, based on the close agreement
      between the two detection methods used, it is concluded that flow cytometry
      provides a rapid and accurate tool for the detection of the relative abundance of
      immuno-labeled target organisms in heterogeneous microbial populations.

PMID- 11234548
TI  - [Cross-cultural comparison of Conners Scales: Can the US-American factorial
      structure be replicated on German clinical sample?].
AB  - OBJECTIVE: International networks in child psychiatry research increasingly rely
      on the cross-cultural generalizability of commonly used questionnaire factor
      structures. The aim of this study is to analyze whether the U.S. factor structure
      of the Conners Parent Rating Scale (CPRS) can be replicated in a German clinical
      sample. METHOD: A German child psychiatry sample of 1394 children children and
      adolescents was randomly splitted into halves. One sub-sample was used to
      calculate a German factor model by means of exploratory factor analysis. This
      model is tested in comparison with he U.S. model constructed according to Conners
      (1989) in the second sub-sample by means of a confirmatory factor analysis
      (LISREL 8). RESULTS: 87% of the path relations in the German and U.S.-American
      models are identical. Both models show limitations with regard to their
      predictive power. As expected, the goodness of fit indices for the German model
      are somewhat better than for the U.S. model (GFI = .81; AGFI = .75 versus GFI =
      .76; AGFI = .71). CONCLUSIONS: The goodness of fit indices of the CPRS model are
      less satisfactory than those of other studies on the cross-cultural
      generalizability of factor structures of dimensional questionnaires (i.e., De
      Groot et al., 1994). However, this is mainly due to restrictions within the model
      (no multiple factor loadings). With respect to the cross-cultural
      generalizability differences were found in the impulsiveness/hyperactivity scale.
      All other scales could be well replicated.

PMID- 11234549
TI  - [Long-term course of childhood or adolescence onset obsessive-compulsive
      disorder: psychosocial adaptation in adulthood].
AB  - OBJECTIVE: The aim of the study was to investigate the long-term course of
      obsessive-compulsive disorder (OCD) with onset in childhood or adolescence. This
      presentation focuses on the social adjustment of the former patients in
      adulthood. METHODS: Fifty-five out of 116 patients with childhood OCD classified
      according to DSM-IV criteria were interviewed personally using structured
      interviews. Mean age at onset of OCD was 12.5 years, and mean follow-up time was
      11.2 years. RESULTS: Despite the evident burden of mental disorder at the time of
      the follow-up, 76% led their own lives without being overly dependent upon their
      parents. 84% had no problems that impaired either school or their occupation. 73%
      were rated as maintaining satisfying social contacts, but only 54% were in a
      relationship at follow-up. CONCLUSIONS: In agreement with other studies we found
      an association between the level of psychosocial adjustment and the course of
      obsessive-compulsive symptoms. Summing up, social adjustment and psychosexual
      functioning seem to be more impaired than occupational functioning. The
      relatively good adjustment of our sample indicates that most patients have found
      a way of managing their lives, albeit still suffering from mental disorders.

PMID- 11234550
TI  - [Law for psychotherapists: challenges for child- and adolescent psychiatry and
      psychotherapy].

PMID- 11234551
TI  - [Does intelligence make a difference? Spelling and phonological readiness in
      specific and nonspecific reading/spelling disabilities].
AB  - OBJECTIVES: In an investigation involving, 1800 second-to-fourth graders, the
      children were divided into three groups according to their reading and spelling
      achievement and the results of a nonverbal intelligence test: children with
      average achievement in oral reading and spelling, and those with poor
      achievements in both which were either discrepant or non-discrepant to their good
      to-average scores on the intelligence test. METHODS: Results for all three groups
      on a number of spelling tests were compiled to assess two component spelling
      skills: phonological recoding and application of orthographical knowledge.
      RESULTS: Children with either specific or nonspecific reading and spelling
      disabilities performed at the same level of phonological recoding, while both
      groups were worse than younger children of average ability at the same spelling
      level. Children with IQ-discrepant reading and spelling disabilities hat, on the
      other hand, a certain advantage over children with the same number of
      difficulties in spelling but a lower IQ on tasks requiring a knowledge of
      orthography. Though particularly evident in the lower grades, this advantage
      declined with advancing grade level. Additional comparison of the three groups in
      tests of phonological awareness and other phonological skills revealed a similar
      pattern of great differences between the two groups of poor readers and spellers
      and the average children, but slight non-significant differences between children
      with IQ-discrepant and non-discrepant reading and spelling disabilities.

PMID- 11234552
TI  - [Risk for schizophrenia and diagnostic image of cerebral membrane metabolism].
AB  - In recent years neurobiological research on the etiology of schizophrenia has
      became increasingly important. In terms of a vulnerability-stress model,
      structural and functional cerebral alterations in schizophrenics and subjects
      with a genetic risk for schizophrenia are presented together with hypotheses for
      disturbances of neurodevelopment or neurodegeneration developed from these
      implications. A detailed description follows of a neurobiochemical paradigm on
      the disturbance of metabolism of membrane-phospholipids. 31Phosphorous Magnetic
      Resonance Spectroscopy allows the detection of indicators of this possible endo
      phenotype. The possibilities and limitations of this method are explained, as are
      findings up to the present. Finally, it is discussed that specific pre-, peri-
      and postnatal influences on the cerebral metabolism of lipids, and thus on
      cerebral development, may be related to structural and functional cerebral
      changes in schizophrenia.

PMID- 11234553
TI  - [Asperger syndrome: an update].
AB  - OBJECTIVES: Asperger's Syndrome is a pervasive developmental disorder that
      manifest itself at pre-school age. It is characterized by qualitative impairments
      of social interaction, deficits in empathy, motor disturbances, and restricted
      repetitive and stereotyped patterns of behavior, interests and activities. A
      genetic etiology is assumed in context with brain dysfunctions and
      neuropsychological deficits which are all focused upon nonverbal learning, even
      though the general intellectual level is within the normal range. Treatment must
      take into account the individual aspects of each case and is based mainly on
      behavior therapy, group training of social skills, vocational training and
      adaptation, and if necessary, on medication. Medical treatment is indicated in
      the presence of special symptoms such as hyperactivity, aggressive behavior,
      sleep disorders, or depression.

PMID- 11234554
TI  - [Marburg Spelling Training program--results of a brief intervention].
AB  - OBJECTIVES: The Marburg Spelling Training Program was administered to a sample of
      10 spelling-disabled primary school pupils (2nd-4th graders) over three months in
      an individual setting. RESULTS: Statistical analyses yielded significant
      improvements in spelling and reading test performances, but none yet in the
      emotional stress caused by the problems. CONCLUSION: The Marburg Spelling
      Training Program has now proven to be effective not only in long-term, but also
      in short-term intervention.

PMID- 11234555
TI  - Analysis of HLA antigens in Croatian patients with psoriasis.
AB  - In common with most autoimmune diseases, psoriasis is associated with some HLA
      antigens. We studied the distribution of HLA antigens in Croatian patients with
      psoriasis: 108 patients were divided into groups according to family history and
      age of disease onset. HLA antigens were analyzed serologically and HLA-C alleles
      were analyzed using polymerase chain reaction. We found significant increases in
      HLA-A2, -B17, -B37 and -B13 antigens and highly significant increases in HLA
      Cw*0602 and DR7 antigens in psoriatic patients compared with controls. Patients
      with type I psoriasis (early onset, positive family history) showed highly
      significant associations with Cw*0602 [p < 0.00001; relative risk (RR) = 14.45]
      and DR7 (p < 0.00001; RR = 15.09) antigens. Patients with type II psoriasis (late
      onset, no family history) had a significant association with Cw*03 antigen (p =
      0.008; RR = 0.17). In conclusion, HLA-B13, -B17, Cw*0602 and -DR7 antigens are
      associated with a significant risk of psoriasis in the Croatian population and
      the Cw*0602 allele has the strongest association, especially for type I
      psoriasis.

PMID- 11234556
TI  - Assessment of perforin expression in peripheral blood lymphocytes in psoriatic
      patients during exacerbation of disease.
AB  - There are very few data concerning the role played by cell-mediated cytotoxicity,
      particularly at the molecular level, in the course of psoriasis. Both cytotoxic T
      lymphocytes (CTL) and natural killer cells contain in their granules the
      cytolytic protein perforin, a mediator in cell-mediated cytotoxicity reactions.
      The aim of this study was to analyze perforin expression in various sets and
      subsets of perforin-positive peripheral blood lymphocytes in 17 patients with
      chronic psoriasis vulgaris in the exacerbation phase. The results were compared
      with those of an age- and sex-matched healthy control group (n = 21). Perforin
      (intracellular antigen) and cell surface antigens were detected using the
      simultaneous double-staining method. We found a significant increase in perforin
      (P) expression in the patient group for CTL (CD3+P+ cells), which are located
      mostly in the CD8+ population of T lymphocytes (CD8+P+).

PMID- 11234557
TI  - Subclinical microbial infection in patients with chronic plaque psoriasis.
AB  - Epidemiological evidence implicates bacterial infection as a common triggering
      stimulus for psoriasis. Recent studies suggest that continuing, subclinical
      streptococcal and staphylococcal infections might be responsible not only for
      relapse of acute guttate psoriasis but also for a new episode of chronic plaque
      psoriasis. In this study 195 patients suffering from a severe form of chronic
      plaque psoriasis hospitalized between 1996 and 1998 were examined. The presence
      of subclinical microbial infection of the upper respiratory tract was studied by
      the cultivation of pathogens from this area. Patients with other provoking
      factors, such as a positive history of taking any drugs that may exacerbate
      psoriasis, endocrine and metabolic factors, alcohol abuse, trauma, dental focus
      and clinically evident bacterial infection, were excluded. Subclinical
      streptococcal and/or staphylococcal infections were detected in 68% of tested
      patients and in only 11% of the control group. The results of this study indicate
      that subclinical bacterial infections of the upper respiratory tract may be an
      important factor in provoking a new relapse of chronic plaque psoriasis.
      Searching for, and eliminating, microbial infections could be of importance in
      the treatment of psoriasis.

PMID- 11234558
TI  - Atopy and contact sensitization in psoriasis.
AB  - The allergen-specific IgE antibody was determined in 20 men and 120 women with
      psoriasis and the results were correlated with a history of current and previous
      allergic disease. Allergic disease was reported in 21% of the patients, but a
      positive RAST test was obtained in 44%. In chronic plaque-type psoriasis a
      positive RAST test was significantly more common (58%) than in active psoriasis
      (22%). Grass pollen and house dust mite were the most prevalent sensitizing
      allergens, with frequencies of 64% and 53%, respectively in the sensitized
      subjects. Sensitization increased with age and polysensitization was common.
      Contact dermatitis was verified with patch tests in 12 men and 20 woman, of whom
      10 had chronic plaque-type psoriasis and 22 active psoriasis. Tar, nickel
      sulphate, corticosteroid mixture and thiomersal were the most common allergens.
      No irritant reactions were seen at the concentrations used. Atopic allergic
      diseases and contact sensitization were therefore common among our psoriatic
      patients.

PMID- 11234560
TI  - Scanning electron microscopy study of hair shaft disorders in psoriasis.
AB  - Studies on scalp hair from psoriatic lesions have revealed marked irregularities
      in the cuticular pattern. The aim of this study was to investigate the incidence
      of hair shaft disorders in psoriatic patients and to evaluate the possibility of
      a correlation with scalp involvement. We examined hair from 39 psoriatic patients
      using scanning electron microscopy and compared it with hair from a control group
      of 12 healthy people. We confined our observations of the hair fibres to the
      areas nearest the root. Our data confirm previous observations indicating that
      dystrophic changes in hair cuticle cells occur more often in hairs from both
      unaffected and affected skin of psoriatic patients compared with normal subjects.
      No differences were observed between hair shafts taken from affected and
      unaffected psoriatic areas; cuticular breakage and an abraded cuticular surface
      were present only in the hair of psoriatic patients.

PMID- 11234559
TI  - Double-blind, placebo-controlled, randomized, right-left study comparing
      calcipotriol monotherapy with a combined treatment of calcipotriol and
      diflucortolone valerate in chronic plaque psoriasis.
AB  - A double-blind, randomized clinical study was conducted to compare the efficacy
      and tolerability of twice-daily topical calcipotriol treatment with a combination
      treatment of calcipotriol once a day in the morning and diflucortolone valerate
      in the evening. Sixty-three patients with a clinical diagnosis of chronic plaque
      psoriasis and comparable psoriatic lesions on both sides of the body were
      included. After a washout phase of 1 week, psoriatic lesions were treated for 4
      weeks with calcipotriol ointment twice daily on one side of the body and a
      combination of calcipotriol and diflucortolone valerate ointment on the other
      side. The treatment period was followed by a period of 4 weeks without any
      treatment. The psoriasis area and severity index (PASI) was used to compare the 2
      groups. Furthermore, the overall therapeutic results were assessed independently
      by the investigators and by the patients. Both treatment regimens showed a
      significant, nearly identical, reduction in PASI. The mean PASI for calcipotriol
      alone was 5.7 at baseline, 1.9 after 4 weeks of treatment and 3.8 at the end of
      the follow-up period. For combination therapy, these values were 5.7, 1.8 and
      3.8, respectively. There was a statistically significant advantage in favor of
      combined calcipotriol and diflucortolone valerate treatment at weeks 1 and 2 (p <
      0.05); however, at the end of the treatment phase the difference between the 2
      therapies was not significant. Subjective evaluation of efficacy by both the
      investigators and the patients revealed no difference between the 2 treatments.
      The frequency of side effects (e.g. irritation) was low in both groups. In
      conclusion, both therapies were effective for the treatment of chronic plaque
      type psoriatic lesions. The combination of calcipotriol and a topical steroid
      appeared to produce a more rapid clinical response and was shown to be as
      effective as calcipotriol therapy alone.

PMID- 11234561
TI  - Differential diagnosis of myasthenic syndromes.
AB  - Myasthenia-like symptoms and Eaton-Lambert myasthenic syndrome have been reported
      in patients with polymyositis. On the other hand, the muscular involvement in
      myasthenic patients is well established. Thus difficulties in the differentiation
      of patients with polymyositis and myasthenic syndrome and myasthenia with
      myopathy may arise. The aim of this investigation was to re-establish the clues
      for distinguishing between different types of myasthenic syndromes. One hundred
      and twenty five patients took part in this investigation. According to the
      electromyography, biopsy and serum levels of creatine kinase data, the patients
      were subdivided into three groups. The first group consisted of 35 patients with
      data for chronic polymyositis. The second group consisted of 46 patients with
      myasthenia. The third group consisted of 44 patients with myasthenia and
      myopathy. Our data confirm the more often onset of myasthenia with ptosis and of
      myasthenic syndromes in polymyositis-from lower limbs. The bulbar involvement is
      more rare, while the autonomic nervous system involvement and decreased tendon
      reflexes are more common in patients with Eaton-Lambert myasthenic syndrome as
      compared to patients with myasthenia. Bulbar involvement is more typical for
      myasthenia, while four limbs involvement is more common in patients with
      myasthenia and myopathic changes. There are no differences in the typical
      decrementing response between patients with polymyositis, myasthenia or
      myasthenia with myopathic involvement. The Eaton-Lambert myasthenic syndrome is
      quite different and is found only in a small part of polymyositis patients. In
      conclusion the differential diagnosis between myasthenic syndromes in
      polymyositis and myasthenia with muscular involvement is not possible only by
      electromyography.

PMID- 11234562
TI  - The effects of electrical nerve stimulation of the lower extremity on H-reflex
      and F-wave parameters.
AB  - The main purpose of this study was to investigate the effects of electrical nerve
      stimulation on alpha motoneurons excitability. The electrophysiological
      parameters of H-reflex and F-wave were assessed for this object. These
      experiments was performed on ten non-athletic healthy men without neurologic
      disorders with mean age 25.6 years (SD 4.4) and three spastic hemiplegic patients
      with mean age 65.33 years (SD 6.32). In the experimental protocol, electrical
      stimulation (TENS) applied on common peroneal nerve with frequency 99 Hz and
      duration 0.25 ms for 30 minutes. H-reflex and F-wave of the soleus muscle were
      recorded in three stages sequenced immediately, 5 minutes and 10 minutes later
      on. The parameters such as amplitudes and latencies of H-reflex and F-wave were
      compared with the data of first record before stimulation. Finally, after 30
      minutes application of TENS the following results were obtained: 1. The mean peak
      to peak amplitude of H-reflexes and F-waves were significantly decreased after
      application of TENS in normal subjects. (P < 0.05) 2. H/M ratios and F/M ratios
      were significantly decreased after application of TENS in normal subjects. (P <
      0.05) 3. The mean latency of H-reflexes and F-waves were significantly increased
      after application of TENS in normal subjects. (P < 0.05) 4. In spastic patients,
      the mean peak to peak amplitude of H-reflexes and F-waves, H/M and F/M ratios
      were significantly decreased and the mean latencies of H-reflexes and F-waves
      were significantly increased after application of TENS. The reduction of
      amplitude of H-reflexes and F-waves, H/M and F/M ratios demonstrated reduction of
      spasticity in patients group. The above-mentioned parameters are parts of
      electrophysiological indicators about assessment of spasticity.

PMID- 11234563
TI  - Carpal tunnel syndrome in carpet weavers.
AB  - We examined the prevalence of abnormal median nerve conduction within the carpal
      tunnel in carpet weavers. Nerve Conduction Studies (NCS) were performed on both
      hands of 47 subjects. Subjects had worked previously for an average of 8.4 (range
      6-21) years and a mean age of 34.8 (17-55) years. An abnormal median nerve
      latencies and, symptoms associated with carpal tunnel syndrome (CTS) were found
      10 (21.2%) and 2 (4.2%) in the subjects studied, respectively. We conclude that
      the high prevalence of abnormal median nerve conduction without corresponding
      symptoms, may suggest a subclinical entity associated with CTS.

PMID- 11234564
TI  - Effect of facilitation on side-to-side H reflex amplitude ratio.
AB  - Although voluntary facilitation is sometimes necessary to evoke the H reflex,
      relevant data is lacking on side-to-side amplitude ratios in facilitated
      condition. To determine the normal limits of H reflex amplitude ratio in
      facilitation and to assess it's clinical applicability, we performed FCR H reflex
      study in fifty asymptomatic subjects. The lower limit of the amplitude ratio that
      encompasses 97.5% of subjects in facilitation was 0.48. These data suggest H
      reflex amplitude ratio measured in facilitation without averaging is useful for
      the diagnosis of unilateral radiculopathy.

PMID- 11234565
TI  - Electromyographic characteristics at the onset of independent walking in infancy.
AB  - In order to elucidate electromyographic characteristics of infant walking at the
      onset of independent gait, we longitudinally recorded electromyograms from
      muscles of both legs during the learning process of walking in an infant, from
      ten months after birth until about three years of age. We found electromyographic
      characteristics of infant gait up to around one month after learning to walk that
      are not usually seen in adult gait. In stance phase from foot contact until push
      off, the role of the vastus medialis for maintaining stability became clear as a
      slightly squatted position was used to lower the center of gravity. Orderly
      reciprocal or cocontraction patterns of activity in the rectus femoris and biceps
      femoris or in the tibialis anterior and gastrocnemius were found to be related to
      returning the body's center of mass toward its initial position. In the latter
      half of swing phase, the vastus medialis and gastrocnemius showed strong
      activities with the knee extending and ankle plantarflexing for active leg
      extension to prevent falling. These characteristically excessive muscle
      activities in infant walking are considered to express weak muscle strength and
      an immature balancing system. As months and years pass, the muscles become
      stronger and balance matures, obviating the need for so much myoelectric
      activity.

PMID- 11234566
TI  - Phase-dependent modulation of the soleus H-reflex during rhythmical arm swing in
      humans.
AB  - The purpose of this study is to investigate modulation of the soleus H-reflex
      during rhythmic arm swing in humans. Significant depression of the soleus H
      reflex was observed when subjects swung their ipsilateral arms or both arms
      reciprocally during testing. The degree of soleus H-reflex depression appeared
      directly proportional to the speed of the arm swing. This depression was observed
      in the conditioning-testing intervals of 400, 500, and 600 msec during the
      ipsilateral backward arm swing and at the onset of the ipsilateral arm forward
      swing. This phase of depression partially overlapped the phase of depression of
      the soleus H-reflex during walking. However, the pattern of modulation during arm
      swing was not exactly the same as that during walking. Therefore, we concluded
      that the ipsilateral arm swing may partially affect the depression of the soleus
      H-reflex during the arm swing phase of walking but is not responsible for
      depression of the soleus H-reflex throughout the entire walking cycle.

PMID- 11234567
TI  - Blink reflex in hyperthyroidism.
AB  - Although there are studies regarding the effects of thyroid hormones on some
      neurologic reflexes, literature lacks knowledge of the effects of thyroid
      hormones on blink reflex circuits. To understand the behaviour of excess thyroid
      hormone on this circuit that involves synapses in brainstem, we studied
      electrically elicited blink reflexes of 7 patients with hyperthyroidism, 8
      patients with hyperthyroidism who were under therapy and 14 volunteers as control
      by electroneuromyograph. Mean values of the latencies and amplitudes of the R1
      and R2 responses were not statistically different between groups, while the
      duration of R2 response and controlateral R2 response were found shorter in
      patients with hyperthyroidism comparing to the patients under therapy and
      controls. We have thought that these findings might reflect the inhibitor effect
      of the excess thyroid hormone on polysynaptic reflex arc of the blink response.

PMID- 11234568
TI  - Auditory event related potentials relate with the clinical progression in
      idiopathic generalized epilepsy.
AB  - Auditory event related potential (ERP) was studied in 60 patients with idiopathic
      generalized epilepsy and 33 age and sex matched healthy subjects. Thirty nine
      patients came to the control three months later and were reassessed. All auditory
      evoked potential latencies were prolonged in epileptics compared to those of
      healthy subjects. Multiple drug using or history of more than 100 seizures was
      associated with prolonged P3 latency. History of status epilepticus was observed
      together with prolongation of N2 and P3 latencies. Patients using their
      antiepileptic drugs more properly after the first control showed shortened P3
      latency in the second control.

PMID- 11234569
TI  - Sensory nerve area measurements in patients with diabetic neuropathy.
AB  - Sensory nerve potential area measurements may reflect the properties of
      underlying nerve fibres better than amplitude or conduction velocity measures.
      The terminal segment of the sensory curve may contain activity of regenerating
      nerve fibres. The reliability of area measurements of sensory potentials obtained
      with surface recording techniques is unknown. We scanned sural nerve sensory
      potential curves and measured the areas under different parts of the curve in 52
      reference and 73 diabetic polyneuropathy (DPN) patients. The variability of
      repeat testing in reference subjects for total area was 12% and for the terminal
      segmental area (TSA) was 19%. In DPN patients, the total area variability was 17%
      and TSA variability was 24%. This compares to amplitude variability of 8% in
      reference subjects and 10% in patients with DPN. These results demonstrate that
      sensory potential area measurements are feasible, but highly variable. We
      conclude that current clinical trials do not include sufficient numbers of
      patients to show change in area measurements, particularly the area under the
      terminal segment of the curve.

PMID- 11234570
TI  - The reliability of H-reflex recordings in standing subjects.
AB  - OBJECTIVE: Several studies have used the H-reflex to investigate the effect of
      upright stances and locomotion on spinal reflex excitability. The reliability of
      eliciting this reflex during weight-bearing has however yet to be addressed. This
      study was undertaken to determine the reliability of individual differences in
      the H-reflex recorded from healthy subjects during quiet standing. Secondary aims
      of the study were to evaluate individual reliability during prolonged standing,
      and to establish the minimum number of trials required to provide reliable
      measurements of the H-reflex. DESIGN AND PARTICIPANTS: Twenty neurologically
      healthy volunteers participated in a repeated measures design consisting of 8
      blocks of 20 trials evenly distributed over two testing sessions. H-reflex
      recordings were elicited from the subject's dominant side soleus muscle by
      percutaneously stimulating the posterior tibial nerve. Stimuli were presented
      every 10 s, with 2 min seated rest provided between blocks of trials. Peak-to
      peak amplitude of H-reflexes and m-responses determined for individual trials
      were used for subsequent analysis. RESULTS: It was found that the reliability of
      measuring the H-reflex and m-response during quiet standing was extremely robust
      (r = .97 for both measures). This pattern of individual differences remained
      consistent over 80 trials confirming the stability of the measures. High
      reliabilities (r = .96 and .87 for the H-reflex and m-responses respectively)
      were also observed when as few as four trials were analysed. When measures
      obtained during the first session of testing were compared with those obtained
      for session two, the correlation coefficients were generally of a lower order (r
      = .54 to .90). DISCUSSION: The results demonstrate that the H-reflex in quiet
      standing provides high intra-individual reliability, suggestive of a stable
      reflex resistant to potentially confounding postural influences, or other sources
      of biological variation. The between-session reliability underscores the
      difficulty in reproducing conditions between sessions, and emphasises the need
      for within-session comparisons of H-reflex amplitudes. Given the functional
      challenge of maintaining an upright posture, the H-reflex appears to be a well
      maintained and stable phenomenon.

PMID- 11234571
TI  - [Measurement of carbon monoxide in expired breath in prehospital management of
      carbon monoxide intoxication].
AB  - INTRODUCTION: Carbon monoxide detectors are currently used by the French
      prehospital medical teams. These detectors can also be used to measure expired
      breath carbon monoxide concentration. The interest of this measurement has never
      been studied. OBJECTIVE: To evaluate interest of expired breath carbon monoxide
      concentration measurement in the management of prehospital carbon monoxide
      intoxication. STUDY DESIGN: Patients with carbon monoxide poisoning were included
      during 1998. PATIENTS AND METHODS: Four levels of clinical severity: no symptom,
      minor, medium or severe intoxication were defined. Carbon monoxide concentration
      were measured in the expired breath (COHbe) at the place of the intoxication and
      in blood samples collected at the place of the intoxication (COHbs) and at the
      hospital (COHbh). RESULTS: 209 patients were included, 144 had no symptom (55%),
      the value of COHbe was 11.6 +/- 7.5% (mean +/- DS) and the value of COHbh was 4.9
      +/- 3.3%. 91 patients had minor intoxication (35%), the value of COHbe was 16.4
      +/- 7.9% and the value of COHbh was 7.1 +/- 4.5%, 21 patients had sever or medium
      intoxication (8%) the value of COHbe was 26.4 +/- 17.7% and the the value of
      COHbh was 12.8 +/- 9.3%. Results for COHbh were obtained for only three patients.
      Relationship between symptoms and expired breath carbon monoxide and relationship
      between symptoms and carbon monoxide blood concentration on arrival at the
      hospital were significant (p < 0.05). CONCLUSION: Measurement of expired carbon
      monoxide concentration, easy and quick to perform is correlated with clinical
      severity in carbon monoxide poisoning.

PMID- 11234572
TI  - [Practice and complications of spinal anesthesia in African tropical countries].
AB  - OBJECTIVE: To evaluate the risk of the practice of spinal anaesthesia (SA) in
      African tropics. STUDY DESIGN: Prospective study in multiple centres over a two
      years period. PERSONS: Twenty-one anaesthesiologists and anaesthetist nurses
      covering ten African countries. METHODS: Two anonymous questionnaires; the first,
      filled in each anaesthetic problem occurred, to define the type of incident or
      accident, and its circumstances; the second was designed to define the position
      occupied, to quantify the global anaesthetic activity, the number of SA, and to
      value the number of complications or deaths linked to SA. RESULTS: Six
      anaesthesiologists and one anaesthetist nurse replied to the study, covering six
      sites in five different countries (Senegal, Chad, Central African Republic, Niger
      and Madagascar). On the 18,432 anaesthetic acts collected, 2,703 (14.7%) were SA.
      In the well-equipped centres, general anaesthesia was predominant with a
      frequency of over 75%. However in the not so well equipped centres or those which
      supplies were more problematical, SA technique was used with a frequency varying
      from 48.9 to 68.7%. Forty incidents and accidents were reported (1.5%), five led
      to the death of the patient (0.2%). Among the seven cardiac arrests (0.3%), four
      were fatal (0.1%). Eight of the ten accidents and all of the deaths occurred in
      the least equipped centres. Eight of ten accidents happened during emergency
      caesarean sections. All cardiac arrests were preceded by a severe hypovolemia.
      For the four deaths after cardiac arrest, an anaesthetist nurse with isobaric
      bupivacaine 0.5% carried out SA. CONCLUSIONS: This study showed that the practice
      of SA in African tropics was performing in different practice conditions and
      people qualification than they were in France. The frequency of cardiac arrests
      and deaths was respectively five and 20 times more important, in those
      conditions. The first conclusion that can be drawn from this study is that it is
      questionable to use SA for emergency Caesarean section under hypovolemic
      condition. The second is the necessity for specific training on the local
      anaesthesia for anaesthetist nurses but also training to choose the anaesthesia
      best adapted to the surgery, the condition of the patient and the means
      available.

PMID- 11234573
TI  - [Analysis of chest radiographs of patients with thoracic trauma is not influenced
      by a grid nor by the experience of the reader].
AB  - OBJECTIVE: To evaluate the interest of a grid and the experience of the
      interpreter to interpretate the chest radiographs (CRs) of patients with thoracic
      trauma, the reference is the helicoidal computed tomography (HCT). STUDY DESIGN:
      Prospective observational study. MATERIAL: CRs and HCT of 50 thorax trauma
      patients. METHOD: CRs were analysed without a grid (L) and results were compared
      with those obtained in an anterior study with a grid (G). The interpreter were
      residents in anaesthesiology (DESAR; G: n = 6/L: n = 4), residents in radiology
      (DESR; G: n = 3/L: n = 5), senior anaesthesiologists (MAR; G: n = 5/L: n = 4),
      and senior radiologists (MR; G: n = 3/L: n = 5). The reference was the HCT. The
      lectors were compared. RESULTS: The interpretation of the CRs was neither
      influenced by the experience and the specialty of the lector nor by the use of a
      grid. Perhaps the formation is sufficient for the anaesthesiologists to evaluate
      the essential lesions in the trauma patient and treat them.

PMID- 11234574
TI  - [Acute hemolysis following perioperative blood salvage in chldren operated for
      the surgical correction of craniosynostosis].
AB  - We report the case of a 6-month-old child, who suffered from acute haemolysis
      following transfusion of salvaged blood. This complication, of favourable
      outcome, was related to the accidental aspiration of benzalkonium chloride into
      the cell saver. This case emphasizes that any adjunction of antiseptic solution
      is contraindicated during blood saving. The use of a cell saver must be
      associated with written protocols, describing clearly the contraindications,
      precautions of use, and the different steps of use of this method of autologous
      blood transfusion.

PMID- 11234575
TI  - [Oculomotor paralysis and spinal anesthesia].
AB  - We describe a case of a parturient scheduled for Caesarean section in whom
      diplopia from abducens (sixth cranial) nerve palsy followed spinal anaesthesia
      performed with a 25 gauge Whitacre needle. After delivery, the patient
      experienced neckache, diplopia and postural headache successively. These symptoms
      were related to the dural puncture. Despite two consecutive epidural blood
      patches, no improvement of diplopia was observed. In 8 months, the nerve palsy
      had completely resolved.

PMID- 11234576
TI  - [Gas embolism during radical nephrectomy by retroperitoneal laparoscopy].
AB  - A case of CO2 gas embolism occurring during retroperitoneal laparoscopic right
      radical nephrectomy in a 70-year-old-woman is reported. Patient's outcome was
      excellent after venous clamping, fluid loading and application of a positive and
      expiratory pressure. Gas embolism is a well documented complication of
      laparoscopic surgery, but has been rarely described in retroperitoneal
      laparoscopy for urologic procedure. The retroperitoneal surgical site, the major
      surgical procedure with vessel manipulation and the left lateral position seem to
      be the risk factors for gas embolism in this case.

PMID- 11234577
TI  - [Postoperative encephalopathies: thiamine deficiency, an unrecognized etiology].
AB  - We report the case of a patient who experienced a postoperative Wernicke
      encephalopathy 8 days after a left hepatectomy performed for metastasis related
      to a rectal cancer. During the six months before surgery the patient lost 10 kg
      of weight (15%). Moreover, in the postoperative period the patient received
      exclusively 5% dextrose solution intravenously. On the 8th postoperative day, an
      alteration of consciousness, a vertical nystagmus and an ataxia led to consider
      the diagnosis of thiamine deficiency that was then established by the decrease in
      the transcetolase activity of the red blood cells. Vitamin B1 supply improved the
      clinical status rapidly and completely. This observation allows to review
      aetiologies and clinical forms of thiamine shortage. In addition, it stresses the
      detection of exposed patients and the prevention methods.

PMID- 11234578
TI  - [Epidural anesthesia for Cesarean section in a patient with von Hippel-Lindau
      syndrome].
AB  - Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder with variable
      penetrance. It is mainly characterized by haemangioblastomas of the retina and
      central nervous system. Because of physiological effects of uterine contractions,
      labour and spontaneous vaginal delivery increase the risk of disrupting central
      nervous system haemangiblastomas. We report the case of a 28-year-old woman with
      an history of VHL disease who had an epidural anaesthesia for labour and for
      Caesarean section performed because of failure to progress and of fetal distress.
      The overall maternal and neonatal outcomes were excellent.

PMID- 11234579
TI  - [Stab wound of the spinal cord complicated by meningitis and subarachnoid
      fistula].
AB  - We describe a case of penetrating spinal cord injuries in an 20-year-old man
      after stab wound attack. The outcome was complicated with subarachnoid fistula
      and meningitis. The diagnosis and management of these complications are
      discussed.

PMID- 11234580
TI  - [Thrombopenia increased by heparin and danaparoid].
AB  - Pathogenesis, frequency, and management of heparin-induced thrombocytopaenia are
      well-known. They may be related with both unfractioned heparin and low-molecular
      weight heparin. Suspected heparin must be discontinued as soon as the diagnosis
      is established. Orgaran (danaparoid sodium) may be used for management of
      patients with heparin-associated thrombocytopaenia but can itself be associated
      with a thrombocytopaenia. Our case report allows us to catch in mind such a
      crossed complication.

PMID- 11234581
TI  - [Intraoperative ventilatory obstruction by twisting of a reusable coiled
      expiratory breathing tube].
AB  - A case of intraoperative subtotal obstruction of a reusable coiled expiratory
      breathing tube is reported. Partial occlusion by twisting was made possible by
      detachment of the coil from the external face of the tube after multiple
      reprocessings with high drying temperatures. A technique for tube checking before
      reuse is described.

PMID- 11234582
TI  - [Blood transfusion in adults: description of a quality assurance program].
AB  - OBJECTIVES: In 1995, a fatal transfusion complication led to the development of a
      quality-assurance programme (QAP). Initial analysis showed important deficiencies
      in practice patterns for both nurses and physicians. No written guidelines had
      been previously produced. STUDY DESIGN: Evaluation of practice patterns and
      quality-assurance programme. METHODS: A QAP was prepared and implemented, a
      booklet describing completely the transfusion process and institutional policies
      and providing practical information was edited and the medical and non-medical
      personnel was informed and trained on a regular basis. Implementation was
      evaluated during a three-year period by measuring previously defined surrogate
      endpoints of the quality of the transfusion process. RESULTS: Implementation
      became rapidly close to 100% either for well-accepted requirements (i.e.
      patient's identity reporting on transfusion forms) or when physicians were highly
      motivated (i.e. autologous blood transfusion). For other indicators,
      implementation progressed more slowly (i.e. traceability of labile blood
      products) although significant efforts were made to improve the computerised
      system of data collection and although hospital administration showed a very
      positive behaviour. Finally, other indicators showed only partial implementation.
      Several practical barriers (perceived lack of time, excessive increase in writing
      requirements) were described for transfusion checklist or transfusion
      prescription form but more in-depth insufficiencies (patients'information) were
      also observed. CONCLUSION: The success of a change of practice patterns relies on
      hospital administration positive role, education and feedback, written and
      immediately available guidelines, employment of specially trained personnel, long
      standing actions. Future accreditation of hospitals based on well-defined and
      well-implemented procedures will also be a major help to increase the quality of
      the transfusion process.

PMID- 11234583
TI  - [Is autologous transfusion still a current topic].

PMID- 11234584
TI  - [Xenon anesthesia: from myth to reality].
AB  - OBJECTIVE: To analyze the current knowledge concerning xenon anaesthesia. DATA
      SOURCES: References were obtained from computerized bibliographic research
      (Medline), recent review articles, the library of the service and personal files.
      STUDY SELECTION: All categories of articles on this topic have been selected.
      DATA EXTRACTION: Articles have been analysed for history, biophysics,
      pharmacology, toxicity and environmental effects and using prospect. DATA
      SYNTHESIS: The noble gas xenon has anaesthetic properties that have been
      recognized 50 years ago. Xenon is receiving renewed interest because it has many
      characteristics of an ideal anaesthetic. In addition to its lack of effects on
      cardiovascular system, xenon has a low solubility enabling faster induction of
      and emergence from anaesthesia than with other inhalational agents. Nevertheless,
      at present, the cost and arety of xenon limit its widespread use in clinical
      practice. The developement of closed rebreathing system that allowed recycling of
      xenon and therefore reducing its waste has led to a recent interest in this gas.
      Reducing its cost will help xenon to find its place among anaesthetic agents. An
      European multicentric clinical trial under submission will contribute to the
      discussion of the opportunity for xenon introduction in anaesthesia.

PMID- 11234586
TI  - [Gastroscopy-colonoscopy: which chronological order?].

PMID- 11234585
TI  - [A case of unexpectedly difficult intubation explained by imaging].

PMID- 11234587
TI  - [Attitude of Moroccan anesthetists faced with postoperative pain].

PMID- 11234588
TI  - [Concerning the new presentation of Celocurine].

PMID- 11234589
TI  - [Gastroscopy-colonoscopy or colonoscopy-gastroscopy: is it important?].

PMID- 11234590
TI  - [Lumbar plexus block reduces pain and blood loss associated with total hip
      arthroplasty].

PMID- 11234591
TI  - [Pharmacologic interventions in primary prevention: lipid lowering drugs,
      aspirin, antiobesity drugs, and antihypertensive agents].
AB  - Heart disease, particularly coronary heart disease is a major cause of morbidity
      and mortality in developed countries. Cardiovascular disease accounts for more
      than 50% of deaths. Drug therapy is highly effective for treatment of patients
      after a first cardiovascular event (secondary prevention). In contrast,
      introduction of drug therapy for lowering cardiovascular risk before a first
      cardiovascular event (primary prevention) is discussed controversially. The
      number of persons who need to be treated for prevention of one cardiovascular
      event is high and drug therapy in more or less "healthy" people is justified only
      after accurate assessment of potential risks and possible beneficial effects.
      Drug therapy combined with non-pharmacological treatment strategies is considered
      to be appropriate in selected high-risk persons for primary prevention. The
      following article describes potential indications of several drugs, in particular
      cholesterol-lowering therapy, aspirin, drug therapy of obesity and hypertension,
      for use in primary prevention of cardiovascular disease.

PMID- 11234592
TI  - [Cardiologic-psychosomatic primary prevention of coronary heart disease].
AB  - Although there exist many relevant data about the significant influence of
      psychosocial risk factors for coronary artery disease, there is no reliable
      concept for an integrated psycho-somato-social primary prevention for CAD. So
      this article is to be a first attempt on such a psycho-somatic primary
      prevention, based on the well known psycho-social risk factors. Referring to the
      pathological and psycho-physiological effects of these risk factors the need of
      equal assessment of all risk factors will be discussed. There will also be
      introduced a comprehensive risk evaluation and the possibility of a
      psychcardiological consultation.

PMID- 11234593
TI  - [Primary prevention from the viewpoint of social medicine--examples of prevention
      projects].
AB  - Life style factors play an essential role in etiology and prognosis of
      cardiovascular diseases; therefore, from a public health point of view, primary
      preventive measures are of especial importance. Health reports in the form of
      specific health reports (such as the Viennese Men's Health Report, the Lower
      Austrian Public Health Report) represent an important foundation for the matter
      of health promoting projects. In Austria, various preventive projects were
      suggested and successfully carried out because of these reports. Furthermore, the
      introduction of the WEBS organisation (scientific dietary counselling service)
      has shown that professional dietary counselling can indeed induce a change for
      the better in dietary behaviour and selection of foodstuffs. By the establishment
      of the first Austrian Institute for the Treatment of Tobacco and Nicotine
      Addiction (Nicotine Institute Vienna) not only is the diagnosis and treatment of
      tobacco addiction ensured, but it also provides information for the populace and
      those active in the health sector. These social public projects provide a
      valuable contribution to the prevention of cardiovascular diseases.

PMID- 11234594
TI  - [Homocysteine and cardiovascular risk].
AB  - Homocysteine is an amino acid that plays a key role in methionine- and
      homocysteine metabolism. Homocystinuria has been described about four decades ago
      to be an inherited (autosomal recessive) disorder with rapid progressive
      atherosclerosis. Thus, homocysteine has been investigated intensively with
      respect to vascular wall injury and atherogenesis. Folic acid and vitamin B12 are
      cofactors of methioninsynthase, a key enzyme in homocysteine metabolism. Plasma
      levels of homocysteine are higher in patients with coronary artery disease
      documented by coronary angiography than in individuals with normal coronary
      arteries. Supplementation of folic acid is the treatment of choice to lower
      plasma homocysteine concentrations. Improvement in endothelial function could be
      documented in patients with folic acid supplementation. Large scaled clinical
      trials investigating folic acid supplementation in secondary prevention are now
      in progress. Today, homocysteine and its association with atherosclerosis raise a
      lot of questions to be answered. A distinct pathophysiological model linking
      hyperhomocysteinaemia and atherosclerosis is still not available. The presence of
      hyperhomocysteinemia in atherosclerotic vascular disease as a surrogate with no
      pathophysiological relevance itself cannot be ruled out. Routine testing of
      homocysteine levels is not yet recommended. Treatment of patients with folic acid
      or vitamin B for primary and secondary prevention of atherosclerotic vascular
      disease cannot be recommended today, because large scaled intervention trials on
      homocysteine lowering by vitamin B or folic acid are not available yet. Possible
      effects of these interventions on acute vascular events are not known.

PMID- 11234595
TI  - Health-related quality of life and pulmonary function in lung cancer patients
      undergoing medical rehabilitation treatment.
AB  - Treatment for lung cancer results in reduced Quality of Life (QoL) and limited
      lung function are well-known. Yet, there are no results available concerning the
      interaction of objective lung function tests and QoL parameters for lung cancer
      patients during in-patient cancer rehabilitation. This is also true for outcome
      parameters in medical rehabilitation. The aim was to study the impact of lung and
      cardiopulmonary function on QoL (EORTC-QLQ C-30 and SF-36 Health Survey) and to
      identify possible outcome parameters for a rehab program. 56 lung cancer patients
      participated. Inpatient rehabilitation consisted of individual aerobic exercise
      and physical, psychological, social, educational and recreational components and
      only led to a gain of QoL by SF-36 Health Survey sub scales "Vitality" and
      "Mental Health". Lung function parameters improved; yet the correlation between
      lung function and health-related QoL questionnaires was not significant.
      Multivariate analysis for groups with high and low performance in lung
      functioning showed differences in the SF-36 Health Survey "Vitality" and "Mental
      Health" sub-scales. However, patients with high and low functional performance of
      the lungs did not differ in their QoL over time. Health-related QoL and pulmonary
      function therefore seem to be independent dimensions. Thus, for judging the
      outcome and success of medical rehabilitation of lung cancer patients, both, QoL
      and pulmonary function have to be taken into account.

PMID- 11234596
TI  - [Commentary on primary prevention].
AB  - In this brief review current guidelines on prevention of atherosclerotic diseases
      and latest results as well as personal views are presented. It is not my purpose
      to give a complete overview on this subject; however, some important aspects will
      be discussed to keep this subject in the forefront of interest.

PMID- 11234597
TI  - [Supporting post of applied medicine].
AB  - Whilst specialists don't care much about defining themselves, general
      practitioners repeatedly are trying to describe their role in modern medicine.
      Nowadays they prefer to present themselves as gate-keepers at the house of
      medicine. In that paper it is outlined that this isn't a useful idea.

PMID- 11234598
TI  - [Amount and intensity of physical exercise in primary prevention].
AB  - Numerous epidemiological studies have demonstrated an inverse relation between
      physical activity and physical "fitness" on one hand and premature death and the
      risk of chronic disease on the other hand. However, most of these studies showed
      crucial methodological and statistical differences, a fact which caused a lack of
      consensus of dose and intensity of physical activities for "health benefits". The
      optimal amount of physical activity to decrease mortality is in literature stated
      to range between 1,000 and 3,500 motoric kcal per week. Only a few data exist
      concerning the optimal intensity of preventive physical activities. There is some
      indication that only "vigorous" but not "non-vigorous" physical activities are
      associated with decreased mortality. Previous investigations suggest that a
      "threshold-intensity" (e.g. of at least 6 MET of "conditioning physical
      activity") is needed to produce an adequate preventive effect. On the other hand
      it has been documented, that "physical fitness" (endurance capacity) is a
      decisive factor for a decreased mortality. Therefore it may be assumed, that
      physical activities are only efficient for health benefits, if they also result
      in increased physical fitness. Following from this assumption the quality and
      quantity of training in primary prevention has to be adjusted to the individual
      requirements (performance, age, gender, health) of men.

PMID- 11234599
TI  - [Reflections on the preoperative anesthesia evaluation].

PMID- 11234600
TI  - [Survey on the preoperative evaluation in Catalonian surgical centers. II. What
      is the attitude and opinion of the professionals involved?].
AB  - OBJECTIVE: Previous studies have provided evidence of the existence of
      differences in preoperative assessment practices and have questioned the
      usefulness of generalized testing for all patients. The objective of this study
      was to determine the attitudes and opinions of anesthesiologists and surgeons
      about their application of preoperative assessment procedures and their knowledge
      of the scientific principles underlying their practice. SUBJECTS AND METHODS: A
      questionnaire was mailed to 227 specialists in anesthesiology and postoperative
      intensive care, general and gastrointestinal surgery, orthopedic surgery and
      traumatology of all hospitals in Catalonia (Spain) with active operating
      theaters. RESULTS: The overall response rate was 61% of the surveyed population,
      with 86% of the Catalan hospitals represented. The medical literature supports
      the routine performance of a chest x-ray and an ECG in the opinion of 17 and 26%
      of the respondents, respectively. Those two procedures are always ordered by 43
      and 37%, respectively, even if they believe that the medical literature does not
      support generalized application. Legal protection was given as the reason for
      routine ordering of preoperative tests in asymptomatic patients, and 89% believed
      that a protocol for selective preoperative assessment procedures would improve
      efficiency. CONCLUSIONS: This study reveals a discrepancy between the opinions of
      professionals involved in preoperative assessment and their real practice in
      Catalan hospitals, probably influenced by perceived need for legal protection.

PMID- 11234601
TI  - [Infiltration of the surgical wound with local anesthetic for postoperative
      analgesia in patients operated on for lumbar disc herniation. Comparative study
      of ropivacaine and bupivacaine].
AB  - OBJECTIVE: To assess and compare the analgesic efficacy of infiltrating the wound
      with ropivacaine or bupivacaine for postoperative pain after lumbar disk repair.
      PATIENTS AND METHODS: A prospective, randomized double blind study of 45 patients
      undergoing elective surgery for herniated lumbar disk repair under general
      anesthesia. Before the surgical wound was closed, the paraspinal musculature and
      subcutaneous tissue were infused with 30 ml of 0.25% ropivacaine in group I (n =
      15), 30 ml of 0.25% bupivacaine in group II (n = 15) or 30 ml of saline solution
      in group III (n = 15). Ketorolac for supplementary postoperative analgesia was
      made available through a patient-controlled intravenous system. We analyzed the
      degree of pain on a visual analog scale and level of pain relief on a simple
      descriptive scale. RESULTS: No significant differences in demographic data,
      duration of surgery or amount of intraoperative fentanyl administered were
      observed among the groups. Mean time until the first request for analgesia was
      significantly longer in group II than in either groups I or III (164 +/- 53 min
      versus 68 +/- 31 and 38 +/- 14 min, respectively). Significantly less ketorolac
      was used in groups I and II than in group III (58 +/- 20 and 59 +/- 21 mg versus
      118 +/- 32 mg). The mean scores on the visual analog scale were similar in all
      three groups. CONCLUSIONS: In this study, infiltration of the surgical wound with
      0.25% bupivacaine or 0.25% ropivacaine was similarly effective for treatment of
      pain after lumbar disk laminectomy.

PMID- 11234602
TI  - [Robert R. Macintosh and Spain: a productive relationship].
AB  - Through his visit to Spain in 1946, Robert R. Macintosh exercised considerable
      influence on the introduction and development of modern anesthesia in this
      country. This paper reviews the technical advances Mackintosh introduced and
      considers how his visit was one of the most important factors in unleashing the
      development of the profession here. Also reviewed are the other visits Mackintosh
      made in the course of his career. Those trips were less important, with the
      exception of a 1937 visit that inspired the design of the Oxford vaporizer, a
      technical concept based on simplicity, safety and the anesthesiologist's
      experience.

PMID- 11234603
TI  - [Perioperative monitoring using transesophageal echocardiography in a case of
      endocarditis-related tricuspid valve disease].
AB  - The risk of infectious endocarditis is higher for intravenous drug users than for
      patients with either rheumatic disease or valve prostheses. We report the case of
      a 33-year-old woman who self-administered opioid drugs parenterally and who
      developed a clinical picture of infectious endocarditis. Serious involvement of
      the tricuspid valve developed in the form of vegetation requiring surgical
      repair, during which transesophageal echocardiography was used for perioperative
      monitoring.

PMID- 11234604
TI  - [Refractory hypotension sustained during general anesthesia due to chronic
      treatment with angiotensin-converting enzyme inhibitors].
AB  - Perioperative management of angiotensin-converting enzyme inhibitors (ACEI) is
      controversial because of associated hypertensive episodes during induction and
      maintenance of anesthesia. A 71-year-old woman with a non-functioning thyroid
      node was scheduled for thyroid lobectomy. Her medical history included high blood
      pressure and she was being chronically treated with ACEI, which were taken until
      the morning of surgery. After induction of anesthesia, arterial hypotension
      refractory to crystalloid therapy developed and worsened in spite of
      administration of a gelatin-type colloid (Gelafundina). The patient did not
      respond to ephedrine or dopamine and required stabilization with adrenalin in
      continuous perfusion for 12 hours. Later evolution was satisfactory and recovery
      took place without sequelae. We discuss the anesthetic implications of chronic
      ACEI treatment and possible hemodynamic repercussions of associated
      administration with gelatin-type solutions or human albumin.

PMID- 11234605
TI  - [Preoperative prophylactic pacemakers: apropos of their indication in a disputed
      case].
AB  - The criteria for preoperative use of pacemakers are not unanimously agreed upon.
      Certain cases require careful assessment to weigh potential benefits against
      inherent risks in placing the device. Although external transcutaneous
      pacemakers, whose use circumvents the risks of transvenous insertion, have been
      available for years, such devices are not always appropriate, depending on the
      flow disorder involved or the type of surgery that will be performed. We report
      the case of a 75-year-old woman who was a candidate for surgery requiring general
      anesthesia (lumboperitoneal shunt due to chronic adult hydrocephaly). Although
      her condition did not initially call for prophylactic use of a pacemaker before
      surgery, changes soon developed that necessitated insertion of a temporary
      transvenous device for surgery and insertion of a permanent pacemaker the day
      after surgery.

PMID- 11234606
TI  - [Survey on the preoperative evaluation in Catalonian surgical centers. I. What is
      the preoperative routine?].
AB  - OBJECTIVE: To describe the preoperative assessment procedures currently used in
      hospitals in Catalonia (Spain). SUBJECTS AND METHODS: The study population
      consisted of all heads of departments of anesthesiology, general and
      gastrointestinal surgery, orthopedic surgery and traumatology of hospitals and
      clinics in Catalonia with active operating theaters. Information was obtained by
      self-administered questionnaire prepared by an interdisciplinary team. RESULTS:
      Of the 227 questionnaires sent, 139 (61%) were answered and returned. A
      preoperative assessment visit was programmed according to 112 (81%) of the
      respondents and 123 (89.8%) reported following a protocol that included ordering
      preoperative tests. The same tests were ordered for all patients by 25% of the
      respondents. A chest film and an ECG were always ordered according to 61 and 65%,
      respectively, and always when the patient was over a certain age according to 36
      and 32%, respectively. Coagulation and blood sugar tests and a complete blood
      workup were always ordered according to 94%, 95% and 89%, respectively. Tests
      were considered valid for less than six months by most. CONCLUSIONS: This survey
      provides evidence of widespread use of preoperative assessment, although
      application falls short of including all scheduled patients. According to these
      results, selective protocols for ordering complementary preoperative tests are
      rarely applied.

PMID- 11234607
TI  - [Importance of the bibliographic review in the editing of a scientific work].

PMID- 11234608
TI  - [Analysis of the cost effectiveness ratio of an autotransfusion program for
      primary prosthetic knee and hip surgery].

PMID- 11234609
TI  - [Rhabdomyolysis and the seated position during posterior fossa surgery].

PMID- 11234610
TI  - [Survey of the deficit of anesthesiologists in Catalonia and analysis of the
      situation made by 47 department heads].

PMID- 11234611
TI  - Integrated jaw and neck function in man. Studies of mandibular and head-neck
      movements during jaw opening-closing tasks.
AB  - This investigation was undertaken to test the hypothesis of a functional
      relationship between the human temporomandibular and craniocervical regions.
      Mandibular and head-neck movements were simultaneously recorded in healthy young
      adults using a wireless optoelectronic system for three dimensional movement
      recording. The subjects were seated in an upright position without head support
      and were instructed to perform maximal jaw opening-closing movements at fast and
      slow speed. As a basis, a study was undertaken to develop a method for recording
      and analysis of mandibular and head-neck movements during natural jaw function. A
      consistent finding was parallel and coordinated head-neck movements during both
      fast and slow jaw opening-closing movements. The head in general started to move
      simultaneously with or before the mandible at the initiation of jaw opening. Most
      often, the head attained maximum velocity after the mandible. A high degree of
      spatiotemporal consistency of mandibular and head-neck movement trajectories was
      found in successive recording sessions. The head movement amplitude and the
      temporal coordination between mandibular and head-neck movements were speed
      related but not the movement trajectory patterns. Examination of individuals
      suffering from temporomandibular disorders and whiplash associated disorders
      (WAD) showed, compared with healthy subjects, smaller amplitudes, a diverse
      pattern of temporal coordination but a similar high degree of spatiotemporal
      consistency for mandibular and head-neck movements. In conclusion, the results
      suggest the following: A functional linkage exists between the human
      temporomandibular and craniocervical regions. Head movements are an integral part
      of natural jaw opening-closing. "Functional jaw movements" comprise concomitant
      mandibular and head-neck movements which involve the temporomandibular, the
      atlanto-occipital and the cervical spine joints, caused by jointly activated jaw
      and neck muscles. Jaw and neck muscle actions are elicited and synchronised by
      neural commands in common for both the jaw and the neck motor systems. These
      commands are preprogrammed, particularly at fast speed. In the light of previous
      observations of concurrent jaw and head movements during foetal yawning, it is
      suggested that these motor programs are innate. Neural processes underlying
      integrated jaw and neck function are invariant both in short- and long-term
      perspectives. Integrated jaw and neck function seems to be crucial for
      maintaining optimal orientation of the gape in natural jaw function. Injury to
      the head-neck, leading to WAD may derange integrated jaw-neck motor control and
      compromise natural jaw function.

PMID- 11234612
TI  - Ketanserin for the treatment of preeclampsia.
AB  - OBJECTIVE: To compare maternal and perinatal outcome with the use of either
      intravenous ketanserin or dihydralazine in treatment of women with preeclampsia.
      METHODS: The records from January 1989 to January 1997 of all patients receiving
      intravenous ketanserin or dihydralazine as first line antihypertensive therapy
      were reviewed and standardized data forms were completed. 315 charts of patients
      were identified and evaluated for effects on blood pressure, laboratory
      parameters, maternal and perinatal outcome. RESULTS: During the study interval
      169 patients received ketanserin and 146 dihydralazine. Significantly fewer
      antepartum (27% versus 38%, p = 0.04) and postpartum (25% versus 39%, p = 0.01)
      maternal complications were noted in patients receiving ketanserin. Occurrence of
      HELLP syndrome was significantly lower among patients who received ketanserin
      (20%) than among those who received dihydralazine (40%, p = 0.0001). Side-effects
      were reported with significantly higher frequency in patients receiving
      dihydralazine (60%) as compared to those receiving ketanserin (17%, p < 0.0001).
      Perinatal outcome was comparable, however, umbilical cord arterial pH values
      (mean +/- SD) were higher with ketanserin compared to dihydralazine (7.25 +/-
      0.07 vs 7.23 +/- 0.09, p = 0.038). The incidence of placental abruption was
      higher in patients receiving dihydralazine (5.5%) versus those receiving
      ketanserin (0.6%, p = 0.014). CONCLUSION: Ketanserin appears to be a better
      option than dihydralazine for treatment of severe preeclampsia since fewer
      maternal complications and side-effects were observed in patients receiving
      ketanserin.

PMID- 11234613
TI  - 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD-II) activity in human placenta:
      its relationship to placental weight and birth weight and its possible role in
      hypertension.
AB  - It has been assumed that low birth weight and high placenta weight were key
      factors for predicting hypertension in human adulthood. A deficiency in placental
      11 beta-HSD-II enzyme activity was supposed to be the underlying cause. To
      possibly establish 11 beta-HSD-II as a leading factor, we determined 11 beta-HSD
      II activities in 133 healthy pregnancies, 21 proteinuric pregnancies complicated
      by pregnancy-induced hypertension (PIH), 26 non proteinuric PIH pregnancies and
      15 pregnancies complicated by fetal growth restriction (32nd-41st gestational
      week). We could not identify differences in 11 beta-HSD-II activity between
      pregnancies with the rare combination of small babies with big placentas and
      others (p = 0.59; Kruskal-Wallis test). And although there was no correlation
      between 11 beta-HSD-II activity and birth weight, in the control gestational age
      correlated with 11 beta-HSD-II activity (r = 0.22; p < 0.05; Spearman). 11 beta
      HSD-II activity in the proteinuric PIH group was significantly higher than in the
      controls (11.7 pmol/min/mg prot.; range 10-13.2 vs. 7.9; range 7.0-9.1; p <
      0.05). The lowest, but not significant, enzyme activities were in the IUGR group
      (5.8 pmol/min/mg prot.; range 4.0-9.2). In this group, analysis of variance
      detected a correlation between enzyme activity and placental weight. In
      conclusion, we could not confirm that placental 11 beta-HSD-II deficiencies act
      as an indicator for the risk of adult hypertension in small fetuses with large
      placentas. However, in growth restriction 11 beta-HSD-II activity might play a
      role. To clarify the influence in this group, further research is needed.
      Increased 11 beta-HSD-II activities with gestational age in the control may serve
      to sustain fetal adrenal steroid genesis and to prepare the fetus for autonomic
      life.

PMID- 11234614
TI  - Cervical incompetence: the use of selective and emergency cerclage.
AB  - OBJECTIVE: This prospective case series was performed in order to assess
      pregnancy outcome of women with tentative diagnosis of cervical incompetence
      undergoing selective and emergency cervical cerclage. METHODS: Women recruited in
      this case series were divided into two groups. The selective group (n = 13) was
      chosen among pregnant women with a history suggestive of cervical incompetence,
      but no clinical evidence of threatened miscarriage. The definition of cervical
      incompetence was dilatation of internal cervical os with shortening of the cervix
      less than 25 mm and "funnelling" of 25% and more, found on the ultrasound
      examination of the cervix. The emergency group (n = 12) had clinical symptoms of
      threatened miscarriage. After exclusion of infection and in the absence of
      uterine activity they were counseled and offered cerclage. RESULTS: After
      cervical cerclage all women were treated in the same way as per our clinical
      protocol and monitored until delivery. The median gestational age at delivery was
      36 weeks (19-39) in the selective group and 33 weeks (22-38) in the emergency
      group. This difference is not statistically significant. There was 1 miscarriage
      (8%), 5 pre-term deliveries (38%) and 7 term deliveries (54%) in the selective
      group; and 4 miscarriages (33%), 3 pre-term deliveries (25%) and 5 term
      deliveries (42%) in the emergency group. Total neonatal survival was 19/20 (95%)
      if pregnancy exceeded 24 weeks, making perinatal mortality 5%. There was no
      differences between selective and emergency groups (1 of 12 in selective vs. 0 of
      8 in emergency). CONCLUSION: Overall, it can be concluded that both selective and
      emergency cerclage may have some benefits in patients with cervical incompetence.
      However, in the absence of a randomized-controlled study, these beneficial
      effects described cannot be considered as proved.

PMID- 11234615
TI  - Detection of cervical immunoglobulin A in normal pregnancy.
AB  - The aim of our study was to evaluate a feasible method to quantify the
      immunoglobulin A concentration in the cervical mucus of women with a normal
      singleton pregnancy. In 60 immunologic healthy pregnant women cervical mucus
      samples were taken at a random time in pregnancy using an absorbing cylindrical
      cotton-swab stick. In this cervical mucus immunoglobulin A concentration was
      measured by radial immunodiffusion. A vaginal bacterial swab was taken from each
      woman. Concentration of immunoglobulins in maternal serum was estimated. There
      was no statistically significant difference of cervical immunoglobulin A
      concentration between the investigated groups (p = 0.952): 18-24 gestational
      weeks (gw): 52.8 (6.6-258.4) mg/l; 25-29 gw: 89.3 (4.8-193.8) mg/l; 30-34 gw: 55
      (1.4-326) mg/l; 35-40 gw: 59.2 (4-400.9) mg/l. Women with a normal vaginal flora
      showed a significantly higher cervical immunoglobulin A concentration than those
      with a pathological colonization: 92.2 (6.6-400.9) mg/l vs. 42.5 (1.4-326) mg/l
      (p < 0.05). The serum levels of immunoglobulins A, A1, A2, M and G do not
      correlate to cervical immunoglobulin A levels nor to gestational age. In normal
      pregnancy, cervical immunoglobulin A concentration does not change with advancing
      gestational age, but a pathological vaginal colonization seems to be associated
      with decreased immunoglobulin A levels.

PMID- 11234616
TI  - 24 hour-CTG monitoring: comparison of normal pregnancies and pregnancies with
      placenta insufficiency.
AB  - AIMS: Routinely antepartal CTG will be recorded for 30 minutes to obtain normal
      resting phases, a decrease of irregulatory due to hypoxia or to differentiate
      these from each other. In case of early onset of hypoxia first pathological
      findings might only be seen by chance in incidentally recorded CTG. The goal of
      this study was, if a continuous 24 hour-CTG will allow an earlier detection of
      beginning hypoxia in case of placental insufficiency compared to a routine CTG of
      30 minutes. METHODS: 21 normal pregnancies and 17 patients with placental
      insufficiency of > or = 36 weeks had 24 hour-CTG's by means of telemetry. In both
      study groups fetal heart rate (FHR) tracing included a full qualitative and
      quantitative description. Comparison of the results of both groups was done to
      look for early signs of pathological findings concerning reduced fetal well
      being. RESULTS: In comparison to normal pregnancies patients with placental
      insufficiency had in 4.5% oscillation frequency type A and an increase of
      saltatory and silent oscillation. The number of accelerations and Dip 0 was
      significantly reduced as well as accelerations in combination with undulatory
      oscillation. Baseline tachycardia and bradycardia showed significantly increasing
      quantity. CONCLUSIONS: 24 hour-CTG is a good screening method to detect early
      onset of hypoxia in case of beginning placental insufficiency. The failure to
      find any clinically significant difference in the diurnal variation of both
      groups suggests, that less than 24 hour testing is required. 8 hour-CTG could be
      a compromise and a big help to detect a fetus at risk earlier.

PMID- 11234617
TI  - Fetal pulse oximetry: current issues.

PMID- 11234618
TI  - Chlamydia trachomatis infection and the risk of perinatal mortality in Hungary.
AB  - INTRODUCTION: Chlamydial infections of the genital tract are thought to often
      lead to preterm birth, which is the most important perinatal problem in Hungary.
      AIM OF STUDY: A multicenter study was carried out to determine the prevalence of
      Chlamydia trachomatis infection, risk factors for the infection and to relate the
      infection to perinatal mortality, accounting for potential confounding effects.
      METHODS: The nucleic acid hybridization method (PACE2 Gen-Probe) was applied for
      the examination of Chlamydia trachomatis. Logistic regression analysis was used
      to assess risk. RESULTS: A total of 6156 pregnancy women were examined for the
      occurrence of Chlamydia trachomatis. The observed overall rate of chlamydial
      infection was 5.9%. Young age (less than 24 years old) (OR and 95% CI: 1.6 (1.3
      2.0)), unmarried status (1.5 (1.2-1.9)) and the high unemployment rate (2.1 (1.6
      2.7)) were statistically significant predictors of the infection. In logistic
      regression analysis, chlamydial infection (1.9 (1.1-3.3)), high unemployment rate
      (1.5 (1.2-2.2)) and low birth weight (1.7 (1.1-2.7) were significant predictors
      of perinatal mortality. CONCLUSIONS: Testing pregnant women for diseases that can
      be transmitted perinatally is an important part of obstetric care. Screening for
      C. trachomatis of unmarried women under 24 years of age is suggested and need
      increased observation during labor.

PMID- 11234619
TI  - Superior mesenteric artery blood flow velocity in small for gestational age
      infants of very low birth weight during the early neonatal period.
AB  - In order to elucidate intestinal blood flow after birth in infants with
      intrauterine growth retardation, we measured superior mesenteric artery blood
      flow velocity in uncomplicated small for gestational age infants with a birth
      weight of < 1500 g by pulsed Doppler ultrasound in days 1 to 7 of life. Peak
      systolic blood flow velocity, time-averaged mean blood flow velocity and end
      diastolic blood flow velocity in the superior mesenteric artery significantly
      increased with time. The resistance index and relative vascular resistance in the
      superior mesenteric artery significantly decreased after birth. Compared with
      gestational age matched appropriate for gestational age infants and birth weight
      matched appropriate for gestational age ones, peak systolic blood flow velocity,
      time-averaged mean blood flow velocity and end-diastolic blood flow velocity in
      the superior mesenteric artery were lower in the small for gestational age
      infants. The difference between the small for gestational age group and the
      gestational age matched appropriate for gestational age group was statistically
      significant. The resistance index and relative vascular resistance in the
      superior mesenteric artery tend to be higher in the small for gestational age
      group than in the appropriate for gestational age groups. In conclusion, although
      intestinal blood flow velocity in infants with intrauterine growth retardation
      increases after birth, it is lower than appropriate for gestational age infants
      during the early neonatal period.

PMID- 11234620
TI  - Longitudinal observation of deterioration of Doppler parameters, computerized
      cardiotocogram and clinical course in a fetus with growth restriction.
AB  - We report on a fetus with intrauterine growth restriction detected at 27 weeks'
      gestation, who was longitudinally followed up until delivery by cesarean section
      33 days later (31 + 5 weeks) due to severe decelerations in CTG. Longitudinal
      Doppler assessment of the umbilical artery (UA), the middle cerebral artery (MCA)
      and the main branch of the right pulmonary artery (RPA), the ductus venosus (DV)
      and the left coronary artery was compared to clinical course and computerized
      CTG. At first presentation (day--33) increased resistance in both the UA and
      uterine arteries with bilateral notches was found. Absent enddiastolic flow (AED)
      in the UA was found at day--19 and reverse flow (RED) at day--11. The MCA showed
      a decreased pulsatility first at day--19 and again at day--11 together with RED
      in the UA. The RPA initially (day--33) showed increased PI which returned to
      normal values at day--19 but increased again at day--1, when the DV showed RED
      and the coronary arteries became visible. The DV was normal until day--11, then
      its PI began to increase together with occurence of RED in the UA, but reverse
      flow in the DV occurred only on the eve (day--1) of severe decelerations in CTG.
      Short-term variability in computerized CTG was stable at 6 to 7 ms, except for an
      intermediate drop to 4 ms at day--10. Maternal hypertension was found at day--19
      and mild preeclampsia developed at day--12. A reduction of fetal movements was
      noticed at day--5. This report shows that at 29 weeks gestation despite detection
      of AED resp. RED in the UA a prolongation of pregnancy for 19 resp. 11 days is
      possible. In addition to abnormal CTG, late signs of fetal deterioration are
      reverse flow in the DV and visibility of the coronary arteries. The role of
      increased resistance in the main branches of the pulmonary arteries should be
      examined in the future.

PMID- 11234621
TI  - First-trimester ultrasonographic investigation of cardiovascular anatomy in
      thoracoabdominally conjoined twins.
AB  - Options for the treatment of thoracoabdominally conjoined twins are dependent on
      the anatomy of the cardiovascular system. It is important to increase the
      accuracy of diagnosis of conjoined twins with a fused heart. Color Doppler
      imaging performed in a 23-year-old nulliparous Japanese woman at 12 weeks of
      gestation revealed synchronized blood flow in 2 aortic arches arising from a
      single heart. The patient underwent a therapeutic abortion, and the diagnosis of
      conjoined twins with a fused heart was confirmed. Thus, color Doppler imaging is
      useful for investigating the cardiovascular anatomy in conjoined twins suspected
      of having a fused heart, even in an early gestational age.

PMID- 11234622
TI  - Low taurine, gamma-aminobutyric acid and carnosine levels in plasma of diabetic
      pregnant rats: consequences for the offspring.
AB  - Gestational diabetes compromises fetal development and induces a diabetogenic
      effect in the offspring, including the development of gestational diabetes and
      the transmission of the effect to the next generation. Changes are not limited to
      glucose and insulin metabolism, and appear to be modulated by alterations at the
      hypothalamo-hypophyseal axis. In the present work, serum concentrations are given
      for the non-protein amino-acids taurine and gamma-aminobutyric acid (GABA), both
      neurotransmitters essential for normal brain development, and for the endogenous
      neuroprotector carnosine, a known anti-oxydans. Taurine levels are significantly
      below normal values in mildly diabetic mothers, in their fetal and adult
      offspring, virgin and pregnant, and in the fetuses of these pregnant offspring.
      GABA and carnosine levels are at the limit of detection in the diabetic mothers
      and their offspring at every stage. It is concluded that the low taurine, GABA
      and carnosine levels in diabetic mothers and their fetuses might compromise the
      normal structural and functional development of the fetal brain. When adult,
      these offspring present a deficiency of the circulating levels of these
      neurotransmitters involved in the hypothalamo-hypophyseal regulation of insulin
      secretion. This might contribute to the development of impaired glucose tolerance
      and gestational diabetes, thereby transmitting the effect to the next generation.

PMID- 11234623
TI  - Spastic diplegia is not associated with intrapartum hypoxia.

PMID- 11234624
TI  - [Hydrosalpinx in a goat].
AB  - A two year old Swiss Alpine goat was referred to our clinic because of sterility.
      Ultrasound examination revealed a nonechogenic area cranially to the urinary
      bladder. As hydrometra was suspected, the goat was treated repeatedly with PGF2
      alpha. Success of this therapy, however, was unsatisfactory and estrus was
      therefore induced by progesterone in combination with eCG and the goat mated. As
      conception failed and ultrasonography remained unchanged, laparoscopy was
      performed and a fluid filled structure could be located in the region of the
      right oviduct. After ovariohysterectomy and histo-pathological examination of the
      genital organs hydrosalpinx was diagnosed on both sides.

PMID- 11234625
TI  - [Ultrasonography of the parathyroid glands in dogs--a review].
AB  - The purpose of the study was to give an overview over the usefulness of
      ultrasonographic examination of parathyroid glands in dogs. By means of a 10 MHz
      high-resolution linear transducer it was possible to visualize parathyroid glands
      in healthy dogs. There was a positive correlation between body weight and size of
      the parathyroid glands, additionally the likelihood to detect 4 glands increased
      with an increase in body weight. Dogs with chronic renal failure had
      significantly larger parathyroid glands than healthy dogs and dogs with acute
      renal failure. In dogs with hypercalcemia of malignancy either none or
      parathyroids which were small in relation to body weight were detected. In
      contrast visualisation of parathyroid masses in dogs with primary
      hyperparathyroidism was easy due to their increased size and anechoic appearance.
      In dogs with severe azotemia the ultrasonographic examination of the parathyroid
      glands is helpful to differentiate between acute and chronic renal failure, in
      dogs with hypercalcemia to differentiate between hypercalcemia of malignancy and
      hypercalcemia due to primary hyperparathyroidism.

PMID- 11234626
TI  - Veterinary epidemiology--a key to sustainable pig production in Switzerland.
AB  - Sustainable animal production requires a healthy production system including
      healthy animals producing wholesome products. Epidemiology as a discipline is
      concerned with the occurrence of disease or disease indicators in populations as
      well as with factors influencing disease occurrence. By providing this
      information, epidemiology contributes significantly to the development and
      maintenance of healthy livestock. This is illustrated with the example of the
      enzootic pneumonia (EP) eradication programme of Switzerland. A series of
      observational studies were conducted in order to obtain the necessary knowledge
      to implement an area-wide EP eradication programme. The issues of economical
      eradication strategies at the herd level and the risk of re-infections were
      addressed. Simulation modelling and economical analysis were also applied. These
      research projects led to the successful start of a national eradication
      programme. The example of the EP eradication programme illustrates that applied
      epidemiological research provides critical information for the planning,
      implementation and evaluation of disease control programmes and is thus a key
      tool in developing sustainable animal production.

PMID- 11234627
TI  - [Serological survey of Sarcoptes scabies var. suis infection using colostrum
      samples: preliminary results].
AB  - Pig mange was investigated serologically in colostral samples with ELISA using
      Chekit Sarcoptest. This test has already been using to investigate sera samples
      from swine in veterinary practice. A total of 684 sow colostral samples were
      collected from 24 mange free breeding units and 6 units with clinical
      manifestation of mange infestation. The specificity of the test was more than 99%
      and the mean seroprevalence 30% (range 6% to 100%). This simple method will allow
      in the future not only the rapid and certain diagnosis of pig mange but also the
      screening of pig breeding units after eradication of the disease.

PMID- 11234628
TI  - [Determination of hematologic and blood chemical reference values in fattening
      pigs of different ages].
AB  - In swine medicine, the determination of hematology and blood chemistry parameters
      is of primary interest in connection with the detection of herd problems. For the
      evaluation of laboratory results the availability of reference values is a
      prerequisite. So far, no reference values of fattening pigs have been available
      in Switzerland. For this reason, in the present study reference values for
      hematology and blood chemistry were determined for two bodyweight categories, 40
      60 kg (group 1) and 85-110 kg (group 2). Hematocrit, hemoglobin and RBC counts
      were lower in animals in group 1. The number of segmented neutrophils was
      markedly higher in group 1. Lymphocyte counts exceeded neutrophil values in both
      groups. Concentrations of total bilirubin, AST, CK and LDH partly reached very
      high levels due to hemolysis or contamination of the blood samples with muscle
      tissue.

PMID- 11234629
TI  - [Liver sonography and ultrasound-guided puncture of the gallbladder in pigs: new
      possibilities for the diagnosis of mycotoxicosis].
AB  - 60 pigs representing all age groups (suckling pigs, weaner pigs, hogs, gilts and
      sows; thereof 37 females, 2 males, 21 castrated males) were examined by
      ultrasound of the liver and by ultrasound guided gallbladder puncture. The
      visibility of the liver and gallbladder was strongly influenced by the size of
      the animals. The thickness of the abdominal and thoracic walls in older animals
      proved to be a highly ultrasound-absorptive medium, which limited the ability to
      assess the underlying tissue structures. As a result, gallbladder puncture of
      these animals was possible only with a certain degree of technical difficulty.
      The gallbladder puncture procedure itself posed little risk to the animal. The
      primary risk resulted from the general anesthesia required. Autopsy showed no
      pathological findings due to gallbladder puncture with the exception of minimal,
      rapidly healing, local infectious processes. The bile proved to be a suitable
      medium of the detection of mycotoxins and their metabolites. Selective
      accumulation of these toxins in bile provide a more reliable diagnostic tool than
      the standard mycotoxicological tests of feed.

PMID- 11234630
TI  - [Purulent osteomyelitis in fattening pigs].
AB  - Purulent osteomyelitis caused by Arcanobacterium pyogenes was diagnosed in three
      pigs aged between 3 and 4 months by radiological and pathological findings.
      Osteomyelitis was localized in metaphysis and/or epiphysis of limb bones. The
      prevalence of osteomyelitis in swine seems to be underestimated because
      inspection of limb bones is not a routine procedure either at slaughter or at
      necropsy. Osteomyelitis may also have consequences for meat cutting.
      Osteomyelitis can be controlled by prophylactic procedures.

PMID- 11234632
TI  - Perforation of toxic megacolon--the value of the plain radiograph.

PMID- 11234631
TI  - [Diabetes mellitus caused by pancreatitis in a bull].
AB  - This paper describes a 6-year-old Simmental bull with diabetes mellitus. The
      animal was referred to our clinic because of severe weight loss and chronic
      indigestion. Clinical examination revealed markedly disturbed general condition,
      impaired forestomach function and polyuria. There was aciduria, glucosuria and
      ketonuria. The most important biochemical findings were severe hyperglycemia,
      markedly increased activities of hepatic enzymes and severe metabolic acidosis.
      Plasma concentrations of insulin, insulin-like growth factor-I, thyroxine and
      3,5,3'-triiodothyronine were lower than normal, whereas those of glucagon were
      higher than normal. Based on these findings, a diagnosis (secondary) diabetes
      mellitus was made. The bull was slaughtered and histological examination revealed
      mixed cell pancreatitis with severe degeneration of islet cells.
      Immunohistochemical examination of the pancreas showed that very few insulin-,
      glucagon-, somatostatin- and pancreatic polypeptide, insulin-like growth factor-I
      and adrenomedullin-producing islet cells were present.

PMID- 11234633
TI  - The Colleges of Medicine of South Africa statement on HIV/AIDS.

PMID- 11234634
TI  - College of Obstetricians and Gynaecologists of South Africa statement on
      HIV/AIDS.

PMID- 11234635
TI  - Cost-effectiveness of AT1 receptor blockers.

PMID- 11234637
TI  - The Anglo-Boer War--another perspective.

PMID- 11234636
TI  - Confirmation of transmission of Enterocytozoon bieneusi in South Africa.

PMID- 11234638
TI  - KZN 'on the mend' from cholera.

PMID- 11234639
TI  - If you were raped, would you ask for HIV antiretroviral treatment?

PMID- 11234640
TI  - Half Botswana's deaths from AIDS.

PMID- 11234642
TI  - Laboratory services bill approved.

PMID- 11234641
TI  - Alternative medicine here to stay.

PMID- 11234643
TI  - The question of price in medical practice.

PMID- 11234644
TI  - Ethico-legal aspects of the protocol for needlestick injuries.

PMID- 11234645
TI  - Year 2000 health goals, objectives and indicators for South Africa.

PMID- 11234646
TI  - Celecoxib--is it worth celebrating?

PMID- 11234647
TI  - Taboo: why black athletes dominate sport and why we're afraid to talk about it.

PMID- 11234648
TI  - The doctor and the rebels--the diary of Charles Molteno Murray, recorded during
      the 1914 Boer rebellion.
AB  - Just 12 years after the conclusion of the Anglo-Boer war, South Africa was led by
      ex-Boer Generals Botha and Smuts into what was to become the Great War, on the
      side of the British. This was utterly unacceptable to thousands of Boers who had
      engaged in a bitter struggle, against overwhelming odds, to prevent their country
      from becoming part of the mighty British Empire. Led by Generals de Wet, Beyers,
      and de la Rey, Lieutenant-Colonel Maritz and Major Kemp, they took up arms in a
      doomed rebellion, without proper weapons, equipment or organisation--by the time
      they were defeated the casualty figures for both sides exceeded those that would
      later result from the German South West campaign. Charles Molteno Murray, 37
      years old, was a GP in Kenilworth, Cape Town, at the time. His father was an
      Irish immigrant doctor, his mother the daughter of the first Prime Minister of
      the Cape, Sir John Charles Molteno. In spite of having a busy and successful
      practice, with a surgical appointment at Victoria Hospital, Charles Murray
      volunteered for duty and soon found himself in the Orange Free State and northern
      Cape, caring for the wounded and dying of both sides in the rebellion. He kept a
      meticulous record of his experiences, written on loose-leaf pages sent as letters
      to his wife, which were later bound into leather-backed diaries. These diaries
      were passed on to his grandson, Dr Robert Murray, who had them transcribed into
      modern format. They contain details of daily life in the midst of military
      action, and also insights into important and little-publicised events of the Boer
      Rebellion of 1914.

PMID- 11234649
TI  - Drug costs and costly drugs--a way forward.

PMID- 11234650
TI  - Community-based distribution of contraception in South Africa--results of a 2
      year pilot in Winterveldt, North-West Province.

PMID- 11234651
TI  - Ambivalence of primary health care professionals towards the South African
      guidelines for hypertension and diabetes.
AB  - BACKGROUND: Consensus-derived guidelines for hypertension and diabetes management
      were introduced by the National Department of Health to improve quality of care.
      However, the incorporation of guidelines into clinical practice is largely
      dependent on the attitudes of health professionals. OBJECTIVE: To audit the
      responses and examine the attitudes of health professionals in primary care
      towards the diabetes and hypertension care guidelines. DESIGN: Qualitative focus
      group, in-depth discussions and clinic observations. SETTING: Four community
      health centres (CHCs) in the Western Cape. SUBJECTS: Fifteen doctors and 10
      professional nurses. METHODS: The responses of health professionals to the
      guidelines were audited. Their attitudes were evaluated at a single pilot CHC
      using focus group discussions and in-depth interviews. Semi-structured interviews
      based on these themes were conducted at 3 other CHCs. Clinic consultations were
      observed to validate the responses. RESULTS: The guidelines were not
      systematically implemented at local CHCs and individual doctors consulted the
      guidelines infrequently. Several themes were identified as barriers to the
      application of the guidelines, including the consultation process by which the
      guidelines were developed, time constraints, scepticism about durability of the
      guidelines, conflict with local practices, health system problems, and patient
      beliefs. CONCLUSION: The usefulness of passive dissemination of guidelines to
      health professionals in primary care should be reviewed as several attitudinal
      barriers to implementation may exist. Guidelines may be adopted more readily if
      these barriers are addressed.

PMID- 11234652
TI  - Breast cancer incidence and determinants of cancer stage in the Western Cape.
AB  - OBJECTIVE: To describe the overall and age-specific incidence rates for breast
      cancer and determinants of the stage of breast cancer at the time of diagnosis in
      the Western Cape, South Africa. METHODS: Data were derived from a case-control
      study of the association between injectable progestagen contraceptives and breast
      cancer conducted over a 4-year period from January 1994 to December 1997. In all,
      485 cases were drawn from a study population consisting of coloured and black
      women under the age of 55 years, who presented with a first occurrence of
      invasive breast cancer at two tertiary hospitals in Cape Town. A questionnaire
      was administered and information on a large number of variables was recorded.
      RESULTS: The 249 cases who were interviewed during the first 2 years of the study
      constituted the numerator for estimates of incidence rates. The overall incidence
      rate was 23.1 per 100,000 women per year. The incidence rate for coloured women
      was 25.6 per 100,000, almost twice that for black women (14.7 per 100,000). The
      incidence rate in urban areas was 26.6 per 100,000, almost twice that in the
      rural areas (16.3 per 100,000). Stages 1 and 2 accounted for 57.8% of the cases.
      Early stage at diagnosis was significantly associated with a higher educational
      level, membership of a medical aid, residence in an urban area and a positive
      family history. CONCLUSION: The data suggest that there is scope for improvement
      in the detection of the disease through education and access to diagnostic
      measures, particularly in rural and disadvantaged populations.

PMID- 11234653
TI  - A double-blind, placebo-controlled, double-centre study of the effects of an oral
      multivitamin-mineral combination on stress.
AB  - OBJECTIVES: To assess the effects of a multivitamin-mineral combination (Berocca
      Calmag) treatment on stress in a large sample of South Africans. METHOD: This was
      a multiple-dose, double-blind, placebo-controlled, double-centre study. Patients
      were drawn from two centres with high stress levels (Durban and Johannesburg),
      each study recruiting the same number of patients (150) from 1,000 adults with
      predetermined high stress levels. Dropouts from the study were replaced. Study
      medication safety was evaluated by recording adverse events. On day 1 (baseline)
      patients were subjected to an individual in-depth assessment that included a
      biographical questionnaire, four psychological scales, and collateral information
      from close relatives. On day 30 (end of the study period) or at the latest 7 days
      after the last planned medication intake, the assessment was repeated for
      purposes of pre- and post-response comparison. RESULTS: Thirty-three patients
      dropped out and were replaced, leaving 300 patients who completed the study--151
      in group 1 (multivitamin-mineral combination), and 149 in group 2 (placebo).
      There were no statistically significant differences between the two groups
      regarding demographics and baseline stress scores at study entry. Both groups
      improved between baseline and the end of treatment as assessed. The degree of
      improvement was statistically significant and greatest in group 1 for all
      psychometric instruments, with this beneficial effect increasing over the course
      of the day. Subgroup analyses for age (18-44 and 45-65 years), gender and
      ethnicity showed no general effect on the overall study outcome. CONCLUSIONS: The
      multivitamin-mineral combination tested is well tolerated and can be used as part
      of a treatment programme for stress-related symptoms at the recommended dose.

PMID- 11234655
TI  - Stroke in the young in South Africa--an analysis of 320 patients.
AB  - BACKGROUND: Aetiology of young stroke populations varies markedly between
      countries. AIM: We present one of the largest prospective studies of stroke in
      young adults, with specific attention given to aetiology and black-white
      differences to assist with secondary prevention and economic planning. SETTING:
      Durban, KwaZulu-Natal, South Africa. METHODS: Only first occurrence of stroke by
      World Health Organisation definition was recorded in patients who had undergone
      anatomical brain imaging. A hierarchy of investigative modalities divided into
      three tiers was applied and a range of standardised scales was scored for each
      patient. This protocol allowed for quantification of clinical deficit,
      aetiopathogenesis, disability and handicap. Cognitive impairment was evaluated
      separately according to predefined criteria. RESULTS: Young stroke patients (15
      49 years) comprised one-quarter of patients seen at this tertiary referral
      institution (320:1, 260, 25.4%). Significant black-white differences were
      encountered for mean age, risk factors, severity of clinical stroke, topography
      of stroke, severity of neurological deficit (Canadian Neurological scale),
      handicap (Rankin scale), aetiology (Trial of Org 10172 in Acute Stroke (TOAST)
      classification) and frequency and subtype of cognitive impairment. In blacks, HIV
      associated stroke was highest in the otherwise unknown aetiological TOAST
      category. CONCLUSION: In South Africa, race and endemic disease both appear to be
      important determinants of stroke in young adults. Knowledge of these variations
      will streamline the increasingly expensive diagnostic and therapeutic approach.

PMID- 11234654
TI  - Fibro-adenoma of the breast in Nigerian Igbos.
AB  - BACKGROUND: There has been a recent increase in interest in conservative
      treatment of benign disease. OBJECTIVE: To study the epidemiology, clinical
      features and management of fibro-adenoma of the breast in Nigerian Igbos.
      PATIENTS AND METHODS: Patients with breast disease presenting to the author at
      four Nigerian hospitals between 1986 and 1997 were enrolled in a prospective
      study. RESULTS: Patients with breast disease constituted a significant burden in
      general surgical practices, with fibro-adenoma present in 94 out of 284 patients
      with benign disease (33%) and 410 patients with breast disease (23%). The
      accuracy of clinical pre-operative diagnosis is excellent, especially in those
      aged under 25 years. Conservative treatment may be advisable for these patients
      if they can be kept under observation. Other worrisome discoveries include a high
      rate of teenage abortion and a significant delay in seeking medical help that has
      not reduced when compared with a previous study undertaken 30 years ago.

PMID- 11234656
TI  - [Genetics of Parkinson's disease].

PMID- 11234657
TI  - [Personality changes in chronic daily headache: a study in the general
      population].
AB  - BACKGROUND AND AIMS: The prevalence and type of personality disorders in
      unselected patients with chronic daily headache (CDH) are unknown. The aim of
      this study was to analyze the personality profile of patients with CHD is the
      general population. PATIENTS AND METHODS: Eighty-nine patients with CDH taken
      from a sample of 1,883 unselected subjects from the general population completed
      the EPQ-A (Eysenck Personality Questionnaire-Adult). RESULTS: Sixty percent of
      the patients with CDH presented a personality profile with high values in the
      scales measuring both the neurotic component (N scales) and the psychotic
      component (P scale). No significant differences were observed in the percentage
      of patients with high scores in these scales according to the diagnoses of
      transformed migraine (TM) or chronic tension headache (CTH). However, the
      percentage of questionnaires with high or not adapted scores was significantly
      greater in the patients abusing of analgesic drugs than is the non-abusers (82%
      versus 53%). With regard to the personality profile, we found a greater, but not
      significant, percentage of patients with CDH with a high grade of neuroticism in
      comparison with psychoticism (52% versus 36%). There were no significant
      differences in the personality profile between the two main subgroups of CCH, TM
      and CTC: 56% of the patients with TM showed high grade of neuroticism and 47%
      psychoticism versus 52% and 30%, respectively in the case of the patients with
      CTC. Sixty-eight percent of the analgesic abusers presented neurotic features and
      50% psychotic features versus 47% and 32%, respectively, for the non abusers.
      CONCLUSIONS: There is a high percentage of subjects with CDH in the general
      population who present high scores in the scales measuring the two basic
      components of the personality, such as neuroticism and psychoticism. This
      personality profile is still found more frequently in patients presenting
      symptomatic medication abuse.

PMID- 11234659
TI  - [Quality of life and neurologic diseases].
AB  - BACKGROUND: The development reached by many countries of our planet has allowed
      that in them most of the infectious diseases have diminished and that the life
      expectancy is over the 75 years of life. As a result of this, degenerative and
      chronic diseases are every day more prevalent and their treatments are longer and
      complex. To value quality of life in these patients and the effect of the therapy
      on health is at the moment a main goal of public health. OBJECTIVES: To know the
      origin, the evolution, and the theoretical foundation of the concept of the
      quality of life, as well as their measurement methods. On the other hand, to
      describe the characteristics of the different available questionnaires in Spain
      to measure the quality of life, either of generic or specific for neurologic
      illness. MATERIAL AND METHODS: The most important questionnaires which have been
      adapted and validated into Spanish have been revised. An exhaustive revision of
      the bibliography related with quality of life and neurology was carried out, and
      all the questionnaires described in these processes were revised. RESULTS: We
      describe the philosophy and concepts of health, quality of life (QOL) and health
      related quality of life (HRQL). The following generic questionnaires are
      described: the Nottingham Health Profile (NHP), the Sickness Impact Profile
      (SIP), the Medical Outcomes Study Short Form (SF-36), the European Profile of
      Quality of Life (EuroQoL), the Questionnaire of Quality of Life (CCV) and the
      Profile of Life quality in the Chronically ill (PLC). In an exhaustive
      bibliographical revision on quality of life and neurology, 52 indexed papers
      appeared, of those which only twelve were related with those subject. The
      following specific questionnaires are described: Qualite de Vie et Migraine
      (QVM), the Parkinson's Disease Questionnaire (PDQ-39), the Functional Status
      Questionnaire (FSQ), the Quality of Life in Epilepsy Inventory (QOLIE-89) and
      their variant of 31 items. Finally two questionnaires ad hoc are described to
      study migraine and epilepsy. CONCLUSIONS: The incorporation of HRQL measures in
      patients with neurological illnesses is an increasing and valued practice by its
      specialists. We observe that the availability of generic tools to measure the
      HRQL in Spanish is wider every day, although most of these come from other
      cultures. The process continued in their transcultural adaptation and validation
      allows us to have some tools of great reliability and effectiveness that
      facilitate its use. In relation to the specific questionnaires on neurologic
      process, the supply is considerably smaller due to the recent appearance of these
      methods in this clinic area.

PMID- 11234658
TI  - [Physiopathology of parkinsonism and dyskinesias: lessons from surgical
      observations]].
AB  - Current models about the organization of the basal ganglia have provided a
      resurgence of the surgical treatment of Parkinson's disease (PD). Surgical
      experience has served to corroborate many of the predictions supported by the
      model. For instance, hyperactivity of the subthalamopallidal pathway is the key
      feature in PD and its suppression is associated with an improvement of the
      cardinal signs and symptoms of the disease. Parkinsonian rest tremor may be
      related to the oscillatory activity of the subthalamic and pallidal neurons.
      However, some clinical observations can not be entirely explained by the model.
      The most important paradox is the disappearance of levodopa-induced dyskinesias
      after pallidal surgery. This review critically analyzes the validity of the
      current model based on the surgical observations.

PMID- 11234660
TI  - [War wound in an 84-year-old patient].

PMID- 11234662
TI  - Spontaneous brain hemorrhage associated with Lyme neuroborreliosis.
AB  - We present the case of a patient with late neuroborreliosis and a spontaneous
      temporal lobe hemorrhage. Although ischemic stroke and subarachnoid hemorrhage
      have been reported in association with Lyme disease, intraparenchymal brain
      hemorrhage has not been previously described in the course of this disease. The
      patient is a 48-year old male with a progressive spastic paraparesis of months'
      duration who presented acute headache, confusion, severe left hemiparesis with
      sensory deficit and homonymous hemianopsia. A cranial computed tomography scan
      showed an extensive right temporal lobe hemorrhage with subarachnoid invasion.
      Brain angiographic and angio-magnetic resonance imaging studies excluded
      hemorrhage-predisposing vascular abnormalities. Cerebrospinal fluid (CSF) studies
      disclosed mononuclear pleocytosis with elevated protein levels. Both serum and
      CSF anti-Borrelia titers were significantly increased, and serum Western Blot
      showed bands to protein 34 (ops B), 57, 59 and 62. The patient was treated with
      ceftriaxone for 4 weeks, with a favorable outcome. It is suspected that cause of
      the hemorrhage was parenchymatous Lyme-associated vascular damage and/or
      microaneurysmatic rupture.

PMID- 11234661
TI  - [Parkinsonism or Parkinson's disease unmasked by pentoxifylline?].
AB  - Pentoxifylline is a synthetic derivative of xantine which stimulates adenosine
      receptors, inhibit phosphodiesterase and increases cyclic monophosphate
      adenosine. It is also considered a dopaminergic D1 receptor agonist. Worsening of
      patients with Parkinson's disease when taking this product has been reported. On
      the other hand, it is considered that adenosine A2A receptors antagonists have
      antiparkinsonian properties. Four cases of patients with a mean age of 77 years
      who developed a rigid akinetic syndrome following therapy with a mean dose of
      1100 mg/day of pentoxifylline over a mean period of 32 days are presented. Two of
      these patients presented clinical characteristics of drug-induced parkinsonism
      and the other two showed Parkinson's disease. The possibility of pentoxifylline
      causing an imbalance between D1 and D2 receptor stimulation and producing
      pharmacologic parkinsonism, or rather, the possibility of pentoxifylline
      unmasking subclinical Parkinson's disease are discussed.

PMID- 11234663
TI  - [Proliferative granulomatous arachnoiditis: an infrequent form of tuberculous
      myeloradioculopathy].
AB  - Proliferative granulomatous arachnoiditis is an infrequent manifestation of
      central nervous system tuberculosis. The mortality rate is 30%, and there are
      functional sequels in almost all patients. We present the case of a 22-year-old
      woman, immunocompetent that suffered form tuberculous radiculo-myelopathy with
      fatal evolution, which allowed us to confront neuroimaging and neuropathological
      findings. Although serial MR imaging illustrated evolution of lesions, autopsy
      revealed more extensive lesions that those observed in neuroimaging studies. The
      characteristic pathological lesion was an intradural inflammatory exudate with a
      global medullar necrosis. Even through duration of medical treatment is still
      discussed, early diagnosis, complete antituberculous drug regimen and prolonged
      corticosteroid therapy are essential to avoid fatal evolution as occurred in this
      case.

PMID- 11234664
TI  - [Miller-Fisher syndrome associated with a bilateral tegmental protuberant lesion
      of probable vascular origin].

PMID- 11234665
TI  - [Recanalization of the middle cerebral artery evaluated using transcranial
      Doppler and early clinical recuperation during infusion of thrombolytic
      treatment].

PMID- 11234666
TI  - Study of antiphospholipid antibodies in patients treated with antiepileptic
      drugs.
AB  - BACKGROUND: Antiphospholipid antibodies (lupus anticoagulant and anticardiolipin
      antibodies) are associated with a variety of clinical situations, including drug
      intake, but their relationships with antiepileptic drugs have been scarcely
      investigated. OBJECTIVE: To determine the prevalence of antiphospholipid
      antibodies in patients treated with antiepileptic drugs and the associated risk
      of thrombotic events. PATIENTS AND METHODS: We performed the serologic study of
      thirty-six consecutively prospectively recruited epileptic patients treated with
      diverse antiepileptic drugs during 44.38 +/- 8.08 months (mean +/- SD) in which
      antiphospholipid antibodies were determined using cardiolipin and a mixture of
      phospholipid from rabbit brain as antigen for detection of cardiolipin and lupus
      anticoagulant by ELISA and in addition lupus anticoagulant was carried out also
      using coagulometric assays. A clinical evaluation was done in order to determine
      the presence of thrombotic events in the following five years. RESULTS:
      Antiphospholipid antibodies were detected in 43% of these patients, in most of
      them as anticardiolipin antibodies (IgM subtype). The patients did not present
      thrombotic events during the time of the study. CONCLUSION: Antiphospholipid
      antibodies are positive in a high proportion of these patients but thrombosis
      were not found during the study duration. This may be explained by the fact that
      the profile of aCL positivity not associated to positive LA observed in these
      patients does not confer a risk for thrombotic events.

PMID- 11234667
TI  - [Ovulation induction, lupus and antiphospholipids].

PMID- 11234668
TI  - [Low molecular weight heparin and hemorrhagic risk in elderly patients].

PMID- 11234669
TI  - [Monitoring of tinzaparin in a ten day treatment dose in elderly patients].
AB  - PURPOSE: Renal impairment, which is frequently observed in elderly patients,
      raises the question of low molecular weight heparins treatment dose adjustment in
      this population. Thus, we conducted a prospective study to determine whether
      tinzaparin, administered subcutaneously at treatment dose (175 anti-Xa IU/kg)
      once daily for 10 days, does accumulate in patients older than 70 years of age.
      METHODS: Accumulation criteria were an increase of plasma anti-Xa and anti-IIa
      levels determined prior to the first injection and on days 2, 5, 7 and 10. The
      characteristics of the 30 consecutive included patients receiving tinzaparin at
      treatment dose (six men, 24 women) were: age 87.0 +/- 5.9 years (range: 71-96
      years), body weight: 62.7 +/- 14.6 kg (range: 38-90 kg) and creatinine clearance
      40.6 +/- 15.3 mL/min (range: 20-72 mL/min). RESULTS: None of the patients
      required a dose adjustment of tinzaparin over the 10-day treatment period. Anti
      Xa and anti-IIa activity levels on day 2 were 0.66 +/- 0.20 IU/mL (range: 0.26
      1.04 IU/mL) and 0.33 +/- 0.10 IU/mL (range: 0.18-0.55 IU/mL), respectively. These
      levels did not significantly change over the 10 days. These results favor the
      absence of the accumulation effect of tinzaparin. There was no correlation
      between anti-Xa and anti-IIa activities and age, weight, or creatinine clearance.
      Concerning the side-effects, only one minor hematoma at the injection site was
      reported. CONCLUSION: Tinzaparin may thus be administered in older patients with
      renal impairment, at a treatment dose (175 anti-Xa IU/kg/d) for a 10-day
      treatment period, without accumulation effect nor hemorrhagic side-effect in
      patients with creatinine clearance greater than 20 mL/min.

PMID- 11234670
TI  - [Wegener's granulomatosis in the elderly patient].
AB  - PURPOSE: To determine aged-related variations in clinical and biological
      presentation and outcome in Wegener's granulomatosis. METHODS: In a retrospective
      cohort study of 35 patients with a diagnosis of Wegener's granulomatosis, 24
      patients (69%) younger than 60 years of age and 11 (31%) aged 60 years or older
      were compared for clinical and biological characteristics. RESULTS: Clinical
      presentation was the same in the two groups; lymphopenia was more common in the
      elderly group (P > 0.05). Despite a similar treatment regime, outcome was
      significantly worse for the elderly group (> or = 60 years), with a mortality
      rate of 36% versus 8% in the control group. Mortality was essentially due to
      delayed infectious complications, raising the problem of a less intensive
      immunosuppressive treatment after remission.

PMID- 11234671
TI  - [Value of abdominal-pelvic computed tomography in adult rheumatoid purpura].
AB  - PURPOSE: Henoch-Schonlein purpura is a rare eventuality in adulthood. Abdominal
      involvement can worsen the short-term prognosis and justify medical treatment to
      avoid surgery. METHODS: Abdominopelvic computed tomography (CT) was performed in
      six adult patients (four men and two women; age range, 19-74 years) with Henoch
      Schonlein purpura before any treatment. Abdominal symptoms were concomitant with
      the purpuric rash in two cases and followed it in the other cases. RESULTS: The
      small bowel was always involved with a parietal thickening, and the target sign
      was observed in three patients. The lesions were located in the duodenum in two
      patients, the jejunum in two and the ileum in five. Two segments were involved in
      one patient and three segments in another patient. A peritoneal effusion was
      always present. No colonic lesion was discovered on CT. Once the results were
      known, all patients received steroids with initially intravenous
      methylprednisolone in five patients at doses ranging from 80 to 1,000 mg/day. On
      follow-up, none of the patients underwent surgery. CONCLUSION: Abdominopelvic CT
      scan demonstrated signs suggestive of intestinal vasculitis. An underlying
      neoplasia or an eventual other cause of abdominal pain were explored and a
      steroid therapy was then began with a good outcome. Abdominal CT can be helpful
      in the diagnosis of abdominal involvement in Henoch-Schonlein purpura.

PMID- 11234672
TI  - [New lipid formulations of amphotericin B. Review of the literature].
AB  - INTRODUCTION: Amphotericin B (amB) remains the gold standard for treatment of
      invasive fungal infections. Lipid formulations of amB have been developed in an
      attempt to improve both efficacy and tolerability (especially renal toxicity):
      amB lipid complex (ABLC), liposomal amB (AmBisome), amB colloidal dispersion
      (ABCD) and amB in lipid emulsion (Intralipid). This review analyzes the data
      available in the literature. CURRENT KNOWLEDGE AND KEY POINTS: ABLC, AmBisome and
      ABCD are effective in various fungal infections, including invasive
      aspergillosis, systemic candidiasis, cryptococcal meningitis, mucormycosis and
      fusariosis. These formulations are also effective in persistent febrile
      neutropenia and in leishmaniosis. The three formulations show little renal
      toxicity and are safer than conventional amB in this respect. Preliminary data
      are available on amB in Intralipid: infusion-related adverse effects are reduced,
      but few data are available on efficacy in documented mycoses. FUTURE PROSPECTS
      AND PROJECTS: Large-scale comparative clinical trials may clarify issues of
      relative efficacy in various forms of fungal infections.

PMID- 11234673
TI  - [Treatment of cluster headache].
AB  - INTRODUCTION: The cluster headache (CH) is one of the most severe types of head
      pain. It is a typical example of a periodic disease and the International
      Headache Society classification recognizes two forms of this disease: episodic
      and chronic CH. Its prevalence is about 0.1 to 0.4% in the general population.
      CURRENT KNOWLEDGE AND KEY POINTS:  PATHOPHYSIOLOGY: A global hypothesis is still
      lacking to explain the pain, the vasodilation, the autonomic features
      (ipsilateral lacrimation, conjunctiva injection, rhinorrhea, partial Horner
      syndrome, etc.) and the periodicity of the CH. Pain and vasodilation seem
      secondary to an activation of the trigeminal vascular system and the periodicity
      of the attacks is thought to be due to a dysfunction of hypothalamic biologic
      clock mechanisms. Treatment of acute CH attacks. The most effective agents are
      oxygen inhalation and subcutaneous sumatriptan, a 5HT1B and D receptor agonist
      which has vasoconstrictor and anti-neurogenic inflammation properties by blocking
      the release from the trigeminal-sensitive fibers of neuropeptides such as CGRP
      and substance P. With subcutaneous sumatriptan, headache relief is very rapid,
      within 5 to 10 min. Prophylactic treatment of CH: The number of attacks per day
      varies from one to three, but some patients can have four to eight per day and
      acute treatments fail to provide sufficient relief or give rise to side-effects.
      Several different regimens have been proven effective. FUTURE PROSPECTS AND
      PROJECTS: Contraindications and side-effects of the drugs limit the choice of the
      prophylactic treatment: corticosteroids in a tapering course, verapamil and
      methysergide are the most useful treatments of the episodic form. Lithium
      carbonate is more effective for the chronic stage of CH, but side-effects are
      often troublesome. Numerous other medications have been used for prophylaxis:
      valproate, capsaicin, beta-blockers. Unfortunately, double-blind studies are
      often lacking and are difficult to realize due to spontaneous variable remission
      of episodic CH. When adequate trials of drug therapies show a total resistance to
      the treatments, surgery may be considered. Radiofrequency trigeminal rhizotomy is
      the treatment of choice with 70% of beneficial effects. Risks and complications
      have to be discussed in balance with the benefit of the different surgical
      procedures.

PMID- 11234674
TI  - [Gene transfer immunotherapy in rheumatoid arthritis: perspectives].
AB  - INTRODUCTION: Tumor necrosis factor (TNF) blocking agents have changed the
      therapeutic approach in rheumatoid arthritis, but a true clinical remission
      remains rare. Gene therapy opens new perspectives in immunotherapy in rheumatoid
      arthritis. This review focuses on the research, data and clinical development in
      rheumatoid arthritis using this strategy. CURRENT KNOWLEDGE AND KEY POINTS: New
      therapeutical targets have been described besides the cytokine inhibitors:
      apoptosis inducers, angiogenesis inhibitors and metalloprotease inhibitors, cell
      activation and signalization have been used in experimental models to inhibit
      arthritis. Gene therapy makes it possible to better understand the
      physiopathology of rheumatoid arthritis and offers the opportunity to induce true
      remissions of experimental arthritis. FUTURE PROSPECTS AND PROJECTS:
      Biotechnology allows the development of new safer vectors which permit long-term
      expression. However, the difficulties to produce high titers and safe vectors
      limit the use of this strategy. The previous clinical data on gene therapy in
      rheumatoid arthritis are limited to feasibility studies. We believe that the
      efficiency of gene therapy will be obtained by combining two or more
      complementary targets.

PMID- 11234675
TI  - Postvaccine vasculitis: a report of three cases.
AB  - INTRODUCTION: Vaccines may be responsible for adverse effects, mainly local
      fugitive and benign reactions. However, few cases of systemic vasculitis have
      been described. We report three new cases, suggesting the responsibility of
      vaccination in starting or reactivating systemic vasculitis. EXEGESIS: We report
      two cases in a 64- and a 68-year-old woman with polymyalgia rheumatica and
      temporal arteritis after influenza and tetanus vaccination respectively, and one
      case in a 30-year-old man with periarteritis nodosa after hepatitis B
      vaccination. CONCLUSION: Knowledge of such complications deserve to be expanded
      in order to: 1) avoid re-immunisations which are likely to result in more serious
      consequences; 2) avoid aggravation or reactivation of a vasculitis; and 3)
      control serology before hepatitis B vaccination in all persons at risk of HBV
      infection.

PMID- 11234678
TI  - [Idiopathic orbital myositis].
AB  - INTRODUCTION: Orbital myositis is a subtype of nonspecific orbital inflammation
      confined to one or more of the extraocular muscles. EXEGESIS: Three female
      patients presented presumed orbital myositis, in each of whom the diagnosis was
      suspected clinically and confirmed by the computed tomography (CT) scan
      appearances. All presented with orbital pain, diplopia and periorbital edema. All
      patients responded to systemic corticosteroid with prompt resolution of symptoms
      and signs, but one patient had recurrent episodes of myositis, leading to the
      prescription of azathioprine. The clinical and radiological constellation of
      findings allowing a definitive diagnosis of the nonspecific orbital inflammatory
      syndrome in most cases is discussed. CONCLUSION: The nonspecific orbital
      inflammatory syndromes are a heterogenous group of conditions and the CT scan is
      a valuable tool in differentiating these conditions. Most cases of idiopathic
      orbital myositis require corticosteroids, but therapeutic alternatives to
      corticosteroids in refractory diseases are warranted.

PMID- 11234677
TI  - [Psychological and behavioral disorders with good outcome in neurosarcoidosis].
AB  - INTRODUCTION: Neurological involvement is observed in 5% of cases of sarcoidosis
      and includes impairment of the central nervous system, the meninges, and the
      cranial and peripheral nerves. Besides neurological defects, cognitive impairment
      may be encountered ranging from isolated memory defect to dementia. EXEGESIS: We
      report a case of neurosarcoidosis occurring in a 40-year-old woman, a native of
      Reunion Island, with initial meningeal and hypophyseal involvement. Three years
      later, while treated with low dose prednisolone and methotrexate, she presented a
      paranoid state associated with cognitive impairment of frontal type and severe
      behavioral disturbances. After 2 years of high dose steroid treatment associated
      with hydroxychloroquine, her behavioral status improved, allowing social and
      familial reinsertion. CONCLUSION: In our observation, sarcoidosis was revealed
      through a central neurological impairment, with chronic meningitis, facial nerve
      palsy, and, finally, through psychiatric symptoms and severe behavioral
      disturbances. A slow favorable outcome was obtained using high dose
      methylprednisolone and hydroxychloroquine with total regression of behavioral
      disturbances but with persisting cognitive alteration.

PMID- 11234679
TI  - [An abnormal aorta...].

PMID- 11234676
TI  - [Behcet's disease manifested as a intracranial aneurysm].
AB  - INTRODUCTION: Mostly venous (95% of all vascular complications), and less
      frequently arterial (2 to 7% of all cases), vascular complications are
      commonplace in Behcet's disease (23 to 64% of the patients, depending on the
      series). Arterial complications are stenosis, occlusions and especially severe
      due to their unpredictable rupture risk, aneurysms. Intracranial aneurysms
      associated with Behcet's disease are exceptional. Until now, only ten cases have
      been published. EXEGESIS: We report the case of a 36-year-old patient of Armenian
      origin in whom the diagnosis of Behcet's disease was made after a subarachnoid
      hemorrhage caused by the rupture of a left superior cerebellar artery aneurysm.
      The endovascular treatment of the aneurysm was associated with an
      immunosuppressive treatment consisting of cyclophosphamide, corticoids and
      colchicine. Within a 6-month period of follow up the evolution has been
      favorable. This is the first published case report of Behcet's disease associated
      with an aneurysm of the posterior circulation treated endovascularly. A review of
      the literature is also included. CONCLUSION: Intracranial aneurysms are an
      exceptional but nevertheless severe localization of vascular complications in
      Behcet's disease. As in all other arterial lesions, recurrences are frequent. The
      treatment involves surgical or endovascular treatment that should be associated
      with corticoids and immunosuppressive therapy. Colchicine is useful for the
      prevention of relapses.

PMID- 11234680
TI  - [Cytomegalovirus hepatitis is never chronic and may hide another!].

PMID- 11234681
TI  - [An unusual cause of renal infarction].

PMID- 11234682
TI  - [Fusobacterium necrophorum septic shock from colonic origin with multiple
      abscesses].

PMID- 11234684
TI  - [Deep venous thrombosis of the arm revealing a congenital Factor XII deficiency].

PMID- 11234683
TI  - [Propionibacterium acnes spondylodiscitis: a case report].

PMID- 11234685
TI  - Expression of vimentin intermediate filament in human odontoblast.
AB  - BACKGROUND: Vimentin (57 Kda) is a cytoskeletal protein. Odontoblasts contain
      vimentin and it seems that this protein may function to keep the organelles and
      the nucleus in a definite place. However little is known about vimentin in the
      cytoskeleton of odontoblast processes. The purpose of the present study was,
      therefore to immunolocalize vimentin intermediate filament in odontoblast body
      and process in order to clarify the distribution of this cytoskeletal element.
      METHODS: 12 extracted intact premolars, from children, were used in the present
      study. Each specimen was decalcified in EDTA. Each tissue portion was embedded in
      paraffin. On sections a monoclonal anti-vimentin antibody was applied. The
      immunoreaction was visualized by ABC technique. RESULTS: Vimentin was expressed
      in the cell body and cell process of odontoblasts, however with a different
      immunolabeling pattern related to the topographical area of observations. In
      odontoblast cell bodies vimentin showed a perinuclear and cytoplasmatic staining.
      In the very initial portion of odontoblast process immunoreaction products for
      vimentin were observed in the core of the process. In the middle zone of dentin
      vimentin immunoreactions products also showed a granular and cross-bridge
      arrangements, and also, vimentin was also detected under the plasma membrane, at
      the periphery of the odontoblast process. Nearby the dentino-enamel junction
      vimentin immunolabeling was appreciated, mainly under the plasma membrane.
      CONCLUSIONS: On the basis of vimentin distribution in the odontoblast process it
      seems plausible to assume that this IF vimentin is important in forming a
      flexible scaffold essential for structuring cytoplasm.

PMID- 11234686
TI  - [Mouth diseases and dental materials: potential for study with cytofluorometry].
AB  - BACKGROUND: The potential dental materials have of inducing mouth diseases is
      well known, and various methods have been developed to investigate this
      phenomenon. Among these there are histological studies of the pulp and
      periodontium exposed to dental materials, both in vivo and in vitro in humans and
      animals. Other studies are based on the clinical observation of the effects
      induced by dental materials. Aim of the paper is to evaluate the use of flow
      cytometry to analyse crevicular fluid to study its content in terms of
      inflammatory cells and inflammation mediators. METHODS: Samples of crevicular
      fluid were collected by aspiration using a bevelled needle mounted on a 5 ml
      syringe from patients without periodontitis and with periodontitis and multiple
      heterogeneous dental restorations. This method was adopted since it allows to
      place the cells of the fluid in suspension. Part of the fluid was analysed by
      cytology and part by flow cytometry. RESULTS: In the patients without periodontal
      disease cytological examination revealed the presence of desquamated epithelial
      cells and colonies of cocci, rods and spirochaetae. In the patients with
      periodontal disease the same examination revealed, besides the above, the
      presence of inflammatory cells. Flow cytometry confirmed the findings of
      cytological examination, thus proving to be an effective method for studying
      crevicular fluid. CONCLUSIONS: This method allows to identify specific
      inflammatory cells or mediators of inflammation in crevicular fluid and may
      therefore prove to be very useful in the study of alterations induced by some
      dental materials at the level of the gingival sulcus.

PMID- 11234687
TI  - [Dental and skeletal malformations: 434 cases of II and III dental skeletal
      class. Our experience and review of the literature].
AB  - BACKGROUND: This study tests the patients who underwent to orthognatic surgery to
      compare the perioperatory treatment and the results with what related by
      international bibliography. METHODS: We have made a retrospective analysis on 434
      patients affected by dentalskeletal malformations and surgically treated at the
      Department of Maxillo-Facial Surgery of the University of Rome "La Sapienza",
      from 1-1-1988 to 31-12-1997. We have examined these data: clinical evaluation of
      patient, pre and post-surgical orthodontic treatment, minimum age for surgical
      correction, surgical technique, use of osseus-synthesis with wire or RIF for
      mobile segment osseus stabilization, use of reference articular plaque and the
      possible association of additional surgical technique during the same time of
      maxillomandibular correction. We have made in all patients orthognatic surgery,
      which consist in osteotomy Le Fort I for upper jaw and sagittal osteotomy for
      mandible. RESULTS: In 25 patients was necessary remove the plaques and the screws
      which have made an infection. In 15 patients we have executed a subsequent
      operation for relapse of the dentalskeletal malformation. In other patients we
      have got a good functional and aesthetical result. CONCLUSIONS: From our study
      result that an exact presurgical analysis and a correct orthodontic-surgical
      treatment have permitted to obtain a good functional and aesthetical result in
      all patients.

PMID- 11234688
TI  - [Distraction osteogenesis of the cranio-maxillo-facial bones].
AB  - Distraction osteogenesis is a surgical technique: its main purpose is to induce a
      mechanically stimulated bone tissue augmentation. A controlled tension, developed
      by a slow and gradual separation of the corticotomized/osteotomized bone
      segments, induces new bone formation and related soft tissue augmentation. In
      this way, we can observe a more harmonious tissue augmentation, better than with
      traditional techniques as osteotomies with grafts. This procedure, initially
      applied in orthopedic field for limb lengthening, is now also applied in the
      cranio-facial field. The most important features of distraction osteogenesis
      consist in the simplicity of execution, the lack of donor site morbidity and the
      simultaneous expansion of bone and related soft tissue. Besides, the technique is
      still at the beginning and requires further acknowledgements, before being
      widespread used to treat cranio-facial malformations. Disadvantages in bone
      distraction are related to the external device and consist in esthetic discomfort
      during treatment, and cutaneous scars. Recently, to solve these problems an
      intraoral distraction device was proposed. Distraction osteogenesis has now an
      expanding role in cranio-facial surgery.

PMID- 11234689
TI  - [Maxillary sinus surgical lift. Summers' technique versus lateral surgical
      approach].
AB  - BACKGROUND: After an extensive review of the literature regarding maxillary sinus
      lift procedures, the authors report the results of a retrospective study carried
      out by the Institute of Oral and Maxillofacial Surgery at the Second University
      of Naples. METHODS: A group of 9 patients aged between 18 and 50 years old,
      including two females, were enrolled in this study. At the preliminary
      evaluation, the sites to be analysed showed a bone height between the residual
      crest and the sinusal membrane not exceeding 8 mm. All patients responded
      positively to specific preimplantation requisites. Commercially pure titanium
      fixtures were used as well as demineralised freeze-dried bovine bone and
      autologous bone graft from the retromolar region. RESULTS: All patients were
      followed for at least 15 months and no clinical check-ups were missed during that
      time. No implant was lost and no cases of spire exposure were reported.
      Postoperative vertical bone resorption was within normal values. CONCLUSIONS:
      Summers technique and its variations with bone grafts of various kinds represents
      a valid aid for edentulous maxillary rehabilitation with scarce osseous resources
      in the postero-superior sectors. It offers a number of advantages compared to the
      traditional technique using an invasive lateral approach and is more acceptable
      to patients. However, in spite of this positive experience, the follow-up in the
      literature still appears to be too short. The authors, are therefore cautious in
      expressing their absolute preference for Summers technique and stress the need to
      wait for further long-term results.

PMID- 11234690
TI  - [Benign parotid lymphoepithelial cysts associated with HIV infection].
AB  - HIV infections are often related with lymphoepithelial benign cysts of the
      parotid gland; these lesions are uncommon and other salivary glands are rarely
      involved. The diagnosis, often difficult, is based on imaging techniques, like
      computed tomography, and pathologic techniques, like fine needle aspiration
      biopsy. The therapeutic approach can be performed by simple aspiration, surgical
      resection, pharmacotherapy, or radiotherapy. Three cases of HIV-related
      lymphoepithelial benign cysts of the parotid gland observed at the Department of
      Maxillofacial Surgery of the "Federico II" University of Naples and at the
      Department of Oral and Maxillofacial Surgery of "La Paz" Hospital of the
      Universitad Autonoma of Madrid are described.

PMID- 11234691
TI  - [Palatal angioleiomyoma. A clinical case].
AB  - A case of angioleiomyoma localized at the level of the soft palate is reported.
      The 31-year-old patient presented a non-pathognomonic clinical picture and the
      anamnestic finding of the relatively slow growth of the neoformation raised
      problems of differential diagnosis in relation to benign growth and lesion of a
      non-neoplastic nature. The differential diagnosis was only obtained with
      histological examination of biopsy material.

PMID- 11234692
TI  - Interstitial cells of Cajal: is their role in gastrointestinal function in view
      of therapeutic perspectives underestimated or exaggerated?
AB  - This manuscript reviews the current views on morphology and function of the
      distinct subpopulations of interstitial cells of Cajal (ICC) in the digestive
      tract and their interrelationships with surrounding cells. Three different
      functions have been postulated so far, i.e. a pacemaker role, a mediator in
      enteric excitatory and inhibitory neurotransmission and a mechanosensor.
      Attention will also be paid to the interstitial cells of Cajal and their possible
      involvement in pathophysiological conditions. Finally, perspectives for
      interstitial cells of Cajal as targets for therapeutic intervention will be
      discussed.

PMID- 11234693
TI  - Design based stereological methods for estimating the total number of objects in
      histological material.
AB  - The principle that formed the basis of the most popular "assumption based"
      stereological methods for counting cells that were available prior to the advent
      of the more recently developed "design based" methods will be described in
      general terms. The major weaknesses inherent in the older methods will be
      described, along with how they have been eliminated by the design based methods.

PMID- 11234694
TI  - Scanning electron microscopic study of the posterior ciliary veins in domestic
      ungulates.
AB  - Vascular corrosion casts of 12 equine, 15 bovine and 50 porcine eyes were studied
      scanning electron microscopically for the presence of posterior ciliary veins.
      These veins drain a postequatorial segment of the choroid and emerge near the
      posterior bulbar pole. They complement the four vorticose veins that emerge near
      or at the equatorial zone of the eyeball and the slender choroidoretinal veins
      that drain the peridiscal area of the choroid. Posterior ciliary veins were
      observed in all equine and bovine eyes examined. In these species they presented
      a large variation in size, number and position. In contrast, posterior ciliary
      veins were only present in two porcine eyes where they were represented by one
      and two vessels, respectively. The morphology and variability of these vessels is
      illustrated and their nomenclature and functional significance are discussed.

PMID- 11234695
TI  - Development of the atrioventricular junctional area in the human heart.
AB  - The structure of the heart has been the subject of many observations since the
      beginnings of medical research. The first information regarding the existence of
      the conduction system of the heart was described by Purkinje and regarding the a
      v node by Tawara. From the history regarding this structure it seems that this
      special system, so relevant to today's invasive cardiologist, is not understood
      in full. With regards to the interventional electrophysiology on the basis of
      histological study we decided to evaluate in detail the morphology and the
      topography of the various portions of the a-v junction. In order to confirm this
      hypothesis we made observations on the autopsy material of 100 normal human
      hearts, both sexes from 16 weeks of foetal life to 105 years of age, in which no
      pathological changes or inborn faults were found. Sections were done containing
      the heart's septum, stained using Masson's method with Goldner's modification.
      This research proves that the atrioventricular junction is a stable structure
      occurring in all hearts, undergoing involutionary changes with age, in which two
      main parts can be differentiated: the node and the bundle. The morphology of the
      node is very complex, because it is composed of three zones: the prenodal, the
      perinodal and the main, differing in cell structure and position. The topography
      of the node is generally stable, as it lies in the interatrial septum and always
      above the septal leaflet of the tricuspid valve. The structure of the bundle, in
      contrast to the node, is more stable and consists of the following parts: the
      penetrating, the non-branching and the branching. Its topography is also stable,
      as it lies in the membranous septum, mainly below the septal cusp of the
      tricuspid valve.

PMID- 11234696
TI  - Scanning electron microscopic study of different hair types in various breeds of
      rabbits.
AB  - The microarchitecture of the cover hairs, wool hairs and tactile (sinus) hairs of
      feral, New Zealand White and Angora rabbits was studied by means of scanning
      electron microscopy. The morphology and variability of the cuticular scale
      patterns, hair cortex, medullary arrangement and profile of the hairs are
      described, illustrated and compared with findings resulting from conventional
      light microscopy, cuticular casting and medullary impregnation. All parameters
      examined in cover hairs presented a considerable variation along the length of
      the hair shaft. In wool hairs, in contrast, only the cuticular scale pattern was
      subject to manifest segmental variation, whereas the shaft diameter, cortical
      profile and medullar composition changed little over the entire length of the
      hair. The tactile hairs of the head were characterised by a round profile of the
      hair shaft, a cylindrical central medullar canal, and a thick cortex covered by
      cuticular scales that were arranged in a waved pattern and oriented transversally
      in relation to the longitudinal axis of the hair. It was concluded that the
      scanning electron microscopic observation of hair samples is a fast and valuable
      method for identifying hair types with useful applications in different
      disciplines such as mammalian biology, the textile industry and forensic
      medicine.

PMID- 11234697
TI  - Types of neurons of the claustrum in the rabbit--Nissl, Kluver-Barrera and Golgi
      studies.
AB  - The studies were carried out on the claustrum of 8 adult rabbits. Four types of
      neurons were distinguished: 1. Multipolar neurons, which have dendritic trunks
      either with conus (multipolar polygonal perikarya) or without conus (multipolar
      rounded perikarya). Both subdivisions of the multipolar neurons have 3-6
      dendritic trunks. Only some branches of these trunks have spines. An axon emerges
      mainly from the cell body, rarely from the initial part of the dendritic trunk.
      2. Bipolar neurons with fusiform or rounded perikarya; they have two dendrites
      covered with spines. An axon originates directly from the cell body or from one
      of the dendritic trunks. 3. Triangular neurons, which have three dendritic
      branches with spines. An axon emerges directly from the soma, often near the
      primary dendritic trunk. 4. Pear-shaped neurons with one or two dendritic trunks
      arise from one pole of the cell body and with an axon that originates from the
      opposite side of the perikaryon. The dendrites are covered with spines.

PMID- 11234698
TI  - Effects of ethanol and arachidonic acid pathway inhibitors on the effectiveness
      of gastric mucosa cytoprotection.
AB  - Cytoprotection in the stomach, consisting in the mucus secretion, mucous
      circulation intensification and bicarbonate secretion to the gastric lumen, is
      highly dependent on the products of arachidonic acid pathway and peroxidative
      antioxidative balance. The aim of the paper was to examine the effects of
      selected inhibitors of arachidonic acid pathway on the natural protective system
      of the gastric mucosa exposed to 50% ethanol. The results show that leukotrienes,
      thromboxane and oxygen reactive forms significantly impair the protective
      function of the gastric mucosa while prostaglandins and antioxidant enzymes act
      protectively.

PMID- 11234699
TI  - Morphometric study of the cornea in human embryos.
AB  - Morphometric study was conducted on 28, serially sectioned staged human embryos.
      The cornea is of equal thickness during its early development (stages 15-17).
      During developmental stages 18 and 19 (7th week) it is thicker in the central
      part. In the last embryonic week the peripheral part of the cornea becomes
      thicker than its central part. The performed study elucidates structural
      differentiation during development of the cornea.

PMID- 11234700
TI  - Morphology, topography and cytoarchitectonics of the otic ganglion in Egyptian
      spiny mouse (Acomys cahirinus, Desmarest).
AB  - Using the thiocholine method of Koelle and Friedenwald and histological
      techniques, the otic ganglion in Egyptian spiny mouse (Acomys cahirinus,
      Desmarest) was studied. The ganglion was found to be a single oval cluster of
      neurocytes, situated at the medial and posterior surface of the mandibular nerve
      just above the maxillary artery. The ganglion is composed of typical ganglionic
      neurons in compact arrangement without a thick connective-tissue capsule.

PMID- 11234701
TI  - Myocardial bridges in the human heart: morphological aspects.
AB  - The structures made of myocardium running most often above the coronary arteries
      are called the muscle bridges. However there is a large number of descriptions of
      that phenomenon, the data are not homogenous. Some papers affirm the occurrence
      of the clinical implications of their existence. The studied material contained
      100 adult human hearts, both sexes, 21 to 76 years of age, preserved in formalin
      ethanol solution. Standard anatomical methods were used in analysis with the help
      of a binocular magnifying glass. The presence of the bridges was confirmed in 41%
      of the researched material, most frequently above the anterior interventricular
      branch. The length of the bridges varies in the range of 2.3-42.8 mm, thickness
      1.0-3.8 mm, angle between long axis of muscle fibres and long axis of the crossed
      vessel from 5 degrees to 90 degrees.

PMID- 11234702
TI  - The value of the heavily T2-weighted sequence in evaluation of the cisternal and
      petroclival segment of the abducent nerve.
AB  - The purpose of the study was to evaluate the usefulness of magnetic resonance
      (MR) in imaging of the cisternal and petroclival segments of the abducent nerve.
      Heavily T2-weighted submillimetric 3D sequence in axial plane, T1-weighted 3D,
      1.5 mm slice thickness sequence in axial plane and TOF sequence were performed on
      16 volunteers. Additionally the reformatted T2-weighted images in sagittal and in
      oblique parasagittal plane parallel to the abducent nerve in the pontine cistern
      were performed. The heavily T2-weighted sequence provides high contrast between
      fluid and other structures. High signal intensity of the cerebrospinal fluid is a
      kind of background for cranial nerves, vessels, meninges as well as for bony and
      fibrous structures. The authors identified the abducent nerve in at least one
      plane of the submillimetric, heavily T2-weighted sequences in 84.4% cases (in
      84.4% in axial plane, 68.8% in sagittal and 84.4% parasagittal parallel to the VI
      th cranial nerve in the pontine cistern). Dorello's canal was identified in 27/32
      abducent nerves (84.4%) on the submillimetric, heavily T2-weighted sequence in
      parasagittal parallel to the abducent nerve in the pontine cistern plane. In
      71.9% (23/32) of cases, the abducent nerve was in contact with the arterial
      vessel in pontine cistern.

PMID- 11234703
TI  - [Thoracic pain].

PMID- 11234704
TI  - [Diagnostic evaluation of dyspnea].
AB  - Dyspnea is a very common symptom and is mostly a benign condition. However
      certain pathologies could lead to the death of the patient. In such cases the
      general practitioner plays an important role in the prompt diagnosis and
      management. Although other conditions may contribute, the cardiac and pulmonary
      organ system is the main causes of dyspnea. A careful history and physical
      examination can lead to a clear diagnosis or a right suspicion. After the
      emergency call the physician will be also involved in the majority of the cases
      in the long term follow-up. This article tries to give cues of diagnosis,
      indications when to hospitalize and keys points for the follow-up.

PMID- 11234705
TI  - [Headaches].

PMID- 11234706
TI  - [Ithaca, return to essential values in general medicine...or three orientations
      for the education of tomorrow's generalists].

PMID- 11234707
TI  - [Abdominal pain].
AB  - The doctor on duty conducting home visits is frequently asked to care for
      patients with non-traumatic severe abdominal pain. For this reason, visiting
      doctors should be able to recognize tell-tale alarm signs, evaluate ailments that
      call for surgical referral to--particularly those that require emergency surgery-
      and, if necessary, perform simple paraclinical exams at the patient's bedside. In
      the case of intense abdominal pain requiring a rapid and effective "analgesia",
      the doctor should be able to administer an opiate, without of the surgical unit
      impairing the judgement. When hospitalisation or referral for surgery is not
      necessary, a re-evaluation at 12 to 36 hours later should be offered.

PMID- 11234708
TI  - [Prognostic approach to the syncopal patient and indication for hospitalization].

PMID- 11234709
TI  - [Endocarditis due to HACEK bacteria. A case report of endocarditis due to
      Kingella kingae].
AB  - Endocarditis is a common disease in hospital practice. Identification of the
      microorganism responsible for the valvular damage is essential to establish the
      prognosis and to determine the optimal antibiotic treatment. In some cases of
      endocarditis the diagnosis is laborious, especially when the responsible
      microorganism is difficult to detect using standard culture techniques. Here we
      report a case of native aortic valve endocarditis due to Kingella kingae, a Gram
      negative organism of the HACEK group. In addition we review 6 other cases of
      endocarditis caused by organism belonging to this group, treated in our hospital
      between 1983 and 1999. Epidemiological studies show that less than 5% of all
      cases of endocarditis are caused by organisms of the HACEK group. The diagnosis
      is often delayed because their slow growth on a standard culture medium. We
      describe clinical and microbiological characteristics of this group of
      endocarditis.

PMID- 11234711
TI  - [Ten questions on the treatment of obesity: from dieting to surgery].
AB  - Advantages and risk of weight reduction achieved by combining diets or unbalanced
      diets with restriction of carbohydrates or fat are discussed. Nutriments differ
      according to their density, their flavour, their satiating, and their thermogenic
      effect. Food is also a source of pleasure and a remedy to frustration. One of the
      problems of dieting is that most patients regain the weight they have lost due to
      a hypometabolism secondary to caloric restriction. Only physical exercise
      together with behavior therapy are able to slow down this weight regain. The
      indication of drug treatment with orlistat, sibutramine and fluoxetin and the
      indication to bariatric surgery are presented. The importance of the prevention
      of obesity by nutrition teaching in schools as well as the necessity of a long
      term treatment as in type II diabetes are underlined.

PMID- 11234710
TI  - [Ten questions on the causes and consequences of obesity: stress hormones].
AB  - In Switzerland, 6% of men and 5% of women are obese (BMI > 30); 33% of men and
      17% of women are overweight (BMI 25-30). Both genetic and environmental factors
      are responsible for obesity. There is an increased risk of C-V disease, diabetes
      and steato-hepatitis in abdominal obesity (abdominal circumference > 102 cm for
      men and > 88 cm for women). There is also an increased level of cortisol, which
      could be due to a difficulty to cope with psycho-social stress. Leptine and
      different hormones play a role in fat storage. Menopause and pregnancy are
      moderate risk factors for obesity. Weight gain may also result from different
      drugs, smoking cessation and stress. Eating disorders such as boulimia and binge
      eating must be diagnosed and treated. Beneficial health effect of weight loss is
      analysed.

PMID- 11234712
TI  - [Upper gastrointestinal hemorrhage, initial management: clinical practice
      recommendations].

PMID- 11234713
TI  - [Role of central telemedicine physicians].

PMID- 11234714
TI  - Marketplace. Gauging quality of comp managed care: the tools are ready, but is
      the will?

PMID- 11234715
TI  - Perspectives. Few governors warn of health cost crunch; tax cut push continues.

PMID- 11234717
TI  - Hearts and minds. How bypass surgery is performed ... and where problems could
      arise.

PMID- 11234716
TI  - Baby, it's you! and you, and you.

PMID- 11234718
TI  - "Om a little teapot...".

PMID- 11234719
TI  - Hurting all over. Patients suffering from fibromyalgia used to be told that it
      was all in their head. Not anymore.

PMID- 11234720
TI  - The ultimate foodie.

PMID- 11234721
TI  - Myocardial infarction with normal coronary angiography compared with severe
      coronary artery disease without myocardial infarction: the crucial role of
      smoking.
AB  - BACKGROUND: Why do some patients suffer acute myocardial infarction (MI) despite
      angiographically normal coronary arteries (NL + MI) whereas others enjoy an acute
      MI-free life despite extensive three-vessel disease (3VD-MI)? The present study
      contrasts these two groups to identify some differences in the risk profile.
      METHODS: In 10,000 patients admitted to the cardiology service, a first MI was
      confirmed in 2356 patients, of whom 1609 underwent coronary angiography. In 77
      patients with MI, coronary angiography was found to be entirely normal (NL + MI,
      77/1609, 4.1%). These were contrasted to 123 patients with severe three-vessel
      coronary disease but no MI (3VD-MI). RESULTS: Patients with NL + MI were 13 years
      younger (42 +/- 8.3 vs 55 +/- 10.5, P < 0.05), with 33 patients (43%) under the
      age 40 years, in contrast to only 9 patients (7.3%) in the 3VD group being this
      age. Patients with NC + MI were more often current smokers (80.5% vs 29% in the
      3VD group; P < 0.01). Patients with 3VD-MI were, on the other hand, more often
      diabetic (54% vs 9% in the NL + MI group; P < 0.01) and had a higher cholesterol
      level (5.6 +/- 1.1 vs 4.9 +/- 1.0 Mmol/l, P < 0.01) as well as a higher incidence
      of chronic stable angina (52% vs 22%; P < 0.01) and heart failure (6% compared
      with 0% in the NL + MI group). Sixty-one out of 77 (79%) NL + MI patients had a
      single risk factor, and in 87%, this was smoking alone. Diabetes mellitus was
      rare and never occurred alone in this group. CONCLUSION: In patients who suffer
      MI despite normal coronary angiography, smoking is a major risk factor: In
      contrast, in patients with extensive coronary artery disease on angiography but
      no MI, diabetes rather than smoking is the dominant risk factor. The findings of
      this study support the view that the risk factors for stable and unstable
      coronary artery disease are different, as reflected by the contrast of the above
      groups at the extremes of the spectrum. Smoking appears to be a major risk factor
      for acute MI (even with normal coronary angiography), whereas diabetes is a major
      risk factor for more severe but more stable coronary artery disease.

PMID- 11234722
TI  - Is there any effect of chronobiological changes on coronary angioplasty?
AB  - AIMS: We hypothesized that If there is a chronobiologic variation in the
      development of acute ischaemic events which is mainly attributed to the tendency
      for thrombus formation in the morning hours, same time dependent variations must
      also be seen in the development of ischaemic events after percutaneous
      transluminal coronary angioplasty (PTCA) and PTCA with stent implantation.
      METHODS: Enrolled in this study were 349 consecutive patients with single vessel
      disease and undergoing elective single vessel angioplasty. Patients had been
      observed for the development of immediate postprocedural ischaemic events.
      Working hours of our laboratory were divided into 2-hourly intervals in order to
      define the ending time of procedure. Analysis of acute complications was carried
      out according to the ending time of procedure. RESULTS: There was no difference
      with regard to clinical presentation, but patients who had complications had
      higher blood cholesterol level (P < 0.05). Patients with stent implantation had
      more adverse events than the PTCA group, but this difference did not reach the
      statistical significance (P = 0.07). The time interval between 10:30 a.m.-12:30
      p.m. was found to be an independent risk factor for the negative outcomes (P =
      0.043, Relative Risk 4838). CONCLUSION: The results of our study have
      demonstrated that postprocedural complications after angioplasty is related to
      the procedure time These patients may be observed more closely for the
      development of immediate postprocedural ischaemic events.

PMID- 11234723
TI  - Changing face of acute myocardial infarction in east London: a prospective cohort
      study of trends in management and outcome in the reperfusion era.
AB  - AIMS: To define the trends in management and outcome of acute myocardial
      infarction over the first decade since the widespread adoption of thrombolytic
      therapy. METHODS: Prospective cohort study of 1737 consecutive patients with
      acute myocardial infarction admitted for coronary care between January 1988 and
      December 1997. RESULTS: Trend analysis with comparison of early (1988-1992) and
      late (1993-1997) cohorts showed significant increments in median age
      (interquartile range) from 62 (54-70) to 64 (55-72) years (P < 0.01) but the
      proportion of smokers fell from 72.7% to 65.8% (P < 0.01). The proportion of
      patients receiving thrombolytic therapy increased from 70% to 78.1% (P < 0.01) as
      median door-to-needle times fell significantly from 92 (60-145) to 68 (45-123)
      minutes (P < 0.01). The proportion of patients discharged on aspirin increased
      from 88.2% to 95.9% (P < 0.01), -blockers increased from 37.4% to 45.8% (P <
      0.01), and angiotensin converting enzyme inhibitors increased from 12.4% to 35.7%
      (P < 0.01). Median hospital stay fell from 9 (7-11) to 6 (5-9) days (P < 0.0001).
      Although the severity of infarction declined, judged by reductions in the
      frequency of Q-wave development from 78.1% to 73.9% (P = 0.01) and peak CK from
      1250 (569-2085) to 1004 (511-1722) IU/l, survival (95% confidence intervals) for
      the early and late cohorts did not change significantly either at 30 days [0.86
      (0.83-0.88) vs. 0.85 (0.83-0.88)] or at 1 year [0.79 (0.76-0.81) vs 0.78 (0.76
      0.81)]. CONCLUSION: The decade from 1988-1997 saw significant changes in the
      demographic characteristics and risk factor profiles of patients with acute
      myocardial infarction admitted for coronary care. We observed trends towards
      increasingly aggressive antithrombotic treatment and early discharge policies,
      with more patients being prescribed drugs for secondary prevention. The combined
      effects of these complex changes on the outcome of infarction defy simple
      analysis and there was no palpable change in short- and longer-term.

PMID- 11234724
TI  - A model for predicting the future incidence of coronary heart disease within
      percentiles of coronary heart disease risk.
AB  - BACKGROUND: We present a method (The CHD Prevention Model) for modelling the
      incidence of fatal and nonfatal coronary heart disease (CHD) within various CHD
      risk percentiles of an adult population. The model provides a relatively simple
      tool for lifetime risk prediction for subgroups within a population. It allows an
      estimation of the absolute primary CHD risk in different populations and will
      help identify subgroups of the adult population where primary CHD prevention is
      most appropriate and cost-effective. METHODS: The CHD risk distribution within
      the Australian population was modelled, based on the prevalence of CHD risk,
      individual estimates of integrated CHD risk, and current CHD mortality rates.
      Predicted incidence of first fatal and nonfatal myocardial infarction within CHD
      risk strata of the Australian population was determined. RESULTS: Approximately
      25% of CHD deaths were predicted to occur amongst those in the top 10 percentiles
      of integrated CHD risk, regardless of age group or gender. It was found that
      while all causes survival did not differ markedly between percentiles of CHD risk
      before the ages of around 50-60, event-free survival began visibly to differ
      about 5 years earlier. CONCLUSIONS: The CHD Prevention Model provides a means of
      predicting future CHD incidence amongst various strata of integrated CHD risk
      within an adult population. It has significant application both in individual
      risk counselling and in the identification of subgroups of the population where
      drug therapy to reduce CHD risk is most cost-effective.

PMID- 11234725
TI  - Psychosocial risk factors for coronary heart disease, their importance compared
      with other risk factors and gender differences in sensitivity.
AB  - BACKGROUND: Few studies have focused on risk factors in women's lives concerning
      psychosocial factors and coronary heart disease (CHD). The present study is one
      of a series in which a wide range of psychosocial factors will be analysed with a
      focus on women. Women and men have been compared with respect to sensitivity to
      psychosocial risk factors regarding CHD. The importance of psychosocial risk
      factors for women, compared with biomedical risk factors has also been studied.
      METHODS: A questionnaire (The Stress Profile) was answered by 538 rehabilitation
      participants (97 women, 441 men) and a reference group (5308 women, 5177 men),
      aged 40-65 years. Psychosocial factors were investigated using means and b
      coefficients. Comparisons between psychosocial and biomedical risk factors were
      made, with respect to the product of the beta-coefficient and the standard
      deviation for each compared risk factor. RESULTS: Significant differences
      appeared concerning five areas: work content, workload and control, physical
      stress reactions, emotional stress reactions and burnout. All showed that the
      relative sensitivity was larger for women than for men. Predictive psychosocial
      risk factors for women with respect to CHD were physical stress reactions,
      emotional stress reactions, burnout, family relationships and daily
      hassles/satisfactions, and they were on approximately the same level as
      biomedical risk factors. CONCLUSIONS: Women appear to be more sensitive than men
      with respect to psychosocial risk factors for CHD, and the predictive ability of
      psychosocial risk factors shows great importance. Actions against unhealthy
      psychosocial conditions are recommended. Both presumptive CHD patients and others
      might benefit from preventive actions, and since women are more sensitive they
      will probably gain more than men.

PMID- 11234726
TI  - Life stress and hypertension.
AB  - The evidence that life event stress, especially occupational stress, may
      contribute to persisting hypertension continues to accumulate. The findings in
      many studies remain significant after controlling possible confounders. This
      report reviews the recent evidence and explains some apparent inconsistencies in
      the literature attributable to different effects of state and trait psychological
      variables.

PMID- 11234727
TI  - Hyperhomocysteinemia and restenosis.
AB  - OBJECTIVE: This study was undertaken to assess the effect of plasma homocysteine
      level on angiographic restenosis 6 months after coronary angioplasty. METHODS:
      The plasma homocysteine level was measured in 100 consecutive patients at the
      time of coronary angioplasty, 56 patients who attended a 6-month follow-up
      angiogram being enrolled to the study; the 44 patients without a control coronary
      angiogram were not enrolled. Patients with and without angiographic restenosis
      were designated as groups A (n = 34) and B (n = 22) respectively. RESULTS: The
      baseline demographic (groups A and B), angiographic (groups A and B) and
      procedural characteristics were similar in both groups. The mean plasma
      homocysteine level (SD) was 15.2 (7.7) and 11.1 (2.5) mumol/l in groups A and B
      respectively (P = 0.007; 95% CI -6.9 to -1.1). With respect to the plasma
      homocysteine level, the upper and the lower thirds were compared by binary
      logistic regression (the lower third homocysteine level being < 10.6 mumol/l and
      the upper third homocysteine level > 14.1 mumol/l). The angiographic restenosis
      rate for the lower and upper tertiles was 47.4% and 89.5% respectively (P = 0.01;
      OR = 9.4; 95% CI 1.6-52.7). After adjustment for age and sex, the statistical
      significance did not change (P = 0.013; OR = 9.43; 95% CI 1.6-54.9). Even after
      adjustment for age, sex, smoking, hypertension, hypercholesterolemia, and
      diabetes mellitus, there was a statistically significant difference between the
      upper and lower tertiles (P = 0.008; OR = 41.3; 95% CI 2.6-635). CONCLUSION:
      Increased plasma homocysteine level and diabetes mellitus were independent risk
      factors for angiographic restenosis after percutaneous transluminal coronary
      angioplasty and coronary stenting.

PMID- 11234728
TI  - Operationalizing knowledge management in health care.
AB  - Being able to leverage the collective clinical knowledge that a health system
      acquires on a daily basis and then apply that knowledge to elevate productivity
      and maintain clinical quality would be nirvana for health system executives.
      Although it is difficult to bring knowledge management to health care, it is not
      impossible. Architects of knowledge management solutions in health care will need
      to balance what an organization hopes to achieve in its market (business
      strategy); how they hope to achieve it (operating strategy); and where
      information technology is needed to enable what they hope to achieve and how they
      hope to achieve it (information strategy).

PMID- 11234729
TI  - The application of knowledge management principles to compliant coding
      activities.
AB  - This article applies the concepts of knowledge management to diagnostic and
      procedural coding performed by health care providers. The process of diagnostic
      and procedural coding is both an art and a science. In particular, the
      information stored away in the minds of individuals performing the coding
      function is ripe for the basis of an effective knowledge Health Information
      Management (HIM) coding management system. In this article, we explore the issues
      and processes that HIM professionals can take advantage of in standardizing the
      coding function.

PMID- 11234730
TI  - Data warehousing: toward knowledge management.
AB  - With rapid changes taking place in the practice and delivery of health care,
      decision support systems have assumed an increasingly important role. More and
      more health care institutions are deploying data warehouse applications as
      decision support tools for strategic decision making. By making the right
      information available at the right time to the right decision makers in the right
      manner, data warehouses empower employees to become knowledge workers with the
      ability to make the right decisions and solve problems, creating strategic
      leverage for the organization. Health care management must plan and implement
      data warehousing strategy using a best practice approach. Through the power of
      data warehousing, health care management can negotiate bettermanaged care
      contracts based on the ability to provide accurate data on case mix and resource
      utilization. Management can also save millions of dollars through the
      implementation of clinical pathways in better resource utilization and changing
      physician behavior to best practices based on evidence-based medicine.

PMID- 11234731
TI  - Knowledge management: white knight or white elephant?
AB  - Knowledge management (KM) is a new management theory embraced by hundreds of
      writers in multiple countries and industries. Although a single fixed methodology
      does not exist, several methodological elements are common to most KM writtings.
      KM has a number of similarities to and differences from quality improvement and
      reengineering. It can be applied to at least two universes in health care
      organizations. Applying KM to a case study in health information management (HIM)
      departments yielded much useful information but also proved unable ultimately to
      resolve the problem being studied. HIM professionals can embrace elements about
      KM that are good and useful, while ignoring elements that do not work.

PMID- 11234732
TI  - Development of the ICD-10 procedure coding system (ICD-10-PCS).
AB  - The International Classification of Diseases 10th Revision Procedure
      Classification System (ICD-10-PCS) has been developed as a replacement for Volume
      3 of the International Classification of Diseases 9th Revision. The development
      of ICD-10-PCS was funded by the U.S. Health Care Financing Administration. ICD-10
      PCS has a multi-axial seven character alphanumerical code structure, which
      provides a unique code for all substantially different procedures and which
      allows new procedures to be easily incorporated as new codes. ICD-10-PCS was
      under development for over five years and the initial draft was formally tested
      and evaluated by an independent contractor. The final version of the ICD-10-PCS
      was released in the spring of 1998. The design, development and testing of ICD-10
      PCS are discussed.

PMID- 11234733
TI  - Dealing with human factors and managing change in knowledge management: a phased
      approach.
AB  - Ten human factors affect the implementation of knowledge management initiatives,
      including fear, cultural change, capturing of tacit knowledge, ease of use,
      stakeholder involvement, and benefits realization. To deal with these factors, a
      phased change management approach is offered, consisting of an assessment,
      strategic planning, organization development, systems design, orientation and
      training, team building, and continuous evaluation and improvement.

PMID- 11234734
TI  - Walmsley's Web watch.

PMID- 11234735
TI  - Transplantation with selected autologous peripheral blood CD34+Thy1+
      hematopoietic stem cells in multiple myeloma: the issue of safety.

PMID- 11234736
TI  - Fifty years of research on tobacco.

PMID- 11234737
TI  - Validation studies in epidemiology: the relative precision of different designs.
AB  - BACKGROUND: In epidemiological studies, estimation of disease exposure
      associations will be biased if the exposure is measured with error. In previous
      papers, we considered the validity of an estimator of the correction factor under
      a variety of assumptions. In particular, in both univariate and bivariate cases,
      we considered the error in estimating the correction factor induced by incorrect
      assumptions on the independent errors of repeated measures, or of different types
      of measures. METHOD: We concentrate our discussion in this paper on the optimal
      design of the validation study based on the asymptotic variance of the estimate
      of the correction factor. Only the univariate situation is considered. We also
      present an example to illustrate the importance of suitable design. RESULTS: The
      value of a good biomarker is demonstrated again.

PMID- 11234738
TI  - Comparison of analytical methods for cluster randomised trials: an example from a
      primary care setting.
AB  - BACKGROUND: Cluster randomisation is commonly used to evaluate educational and
      organisational interventions in primary care. We conducted a study where 66
      general practices in the North East of Scotland were randomised to receive
      guidelines and access to a fast-track investigation service for two common
      urological conditions. Patients were identified from referral letters and
      recruited upon referral to secondary care. Although these urological conditions
      are common in secondary care, the number of referrals per general practice can be
      small; this created a number of issues for the analysis. METHODS: Three general
      approaches in the analysis of cluster randomised trials; the adjustment of
      standard tests; analysis at cluster level; and advanced statistical techniques
      (random effects models and generalised estimating equations) were applied to data
      from the above trial. The effect of the intervention on both a continuous and a
      dichotomous outcome was investigated. RESULTS: Spuriously low P values were
      obtained when conventional tests (which do not account for clustering in the
      data) were applied. Cluster level analysis of the dichotomous outcome with no
      account for cluster size resulted in a different conclusion compared with cluster
      level analysis with weighting, standard tests with adjustment and advanced
      statistical methods. DISCUSSION: Cluster randomised trials are becoming
      increasingly common in primary care. Where recruitment of individual patients is
      generated by referral from primary to secondary care it is likely that the trial
      will suffer from inherent weaknesses: not all clusters randomised contribute to
      the analysis; there is the likelihood of single size clusters and variable
      cluster sizes. Our analysis indicated that the different approaches produced
      consistent results across continuous outcomes, but for dichotomous outcomes in
      the cluster level analysis, failure to weight observations would have resulted in
      a different conclusion.

PMID- 11234739
TI  - Some random-effects models for the analysis of matched-cluster randomised trials:
      application to the Swedish two-county trial of breast-cancer screening.
AB  - BACKGROUND: In the Swedish two-county trial women aged 40-74 years from two
      counties in Sweden were randomised to invitation to mammographic screening for
      breast cancer. METHODS: This paper uses random effects logistic regression models
      to analyse recent data from the trial. The analysis accounts for the structure of
      the trial, where small geographical units are randomised within larger
      geographical strata (blocks of two or three small units that are socio
      economically similar). RESULTS: Fixed effects and a variety of random effects
      models show a strong degree of agreement and yield a significant 29% or 30%
      reduction in breast-cancer mortality. DISCUSSION: Fixed effects and random
      effects models agree for this example, because heterogeneity both between strata
      and within strata between clusters is small and because the effect of treatment
      does not vary much in different strata.

PMID- 11234740
TI  - Measuring injection-site pain associated with vaccine administration in adults: a
      randomised, double-blind, placebo-controlled clinical trial.
AB  - BACKGROUND: Pain at the injection site is one of the most commonly-reported local
      reactions associated with administration of a vaccine, but it has not been
      quantified by a validated instrument for pain measurement. We conducted a
      randomised, double-blind clinical trial to evaluate the measurement
      characteristics of two commonly-used pain questionnaires, the McGill Present Pain
      Intensity (PPI) and the Brief Pain Inventory (BPI) Current Pain Question, in the
      assessment of intramuscular injection-site pain associated with vaccine
      administration. The PPI measures pain on a scale of 0 (no pain) to 5
      (excruciating pain) and the BPI measures pain on a scale of 0 (no pain) to 10
      (pain as bad as you can imagine). METHODS: Two hundred healthy adults were
      randomised to one of the five regimens: tetanus and diphtheria toxoids adsorbed
      (Td), aluminum hydroxide adjuvant (alum), physiological saline, or one of the two
      licensed hepatitis A vaccines, VAQTA, or HAVRIX. Pain assessment was made at
      eight time-points over a 2-day period after injection. RESULTS: The differences
      in the time-averaged pain (+/- standard deviation) on the PPI were statistically
      significant between Td (0.58+/-0.59) and either saline (0.14+/-0.23) (p < 0.005)
      or alum (0.22+/-0.35) (p < 0.01). Reported time-averaged pain were significantly
      lower for VAQTA than HAVRIX (p = 0.028). Similar differences were observed for
      the BPI. CONCLUSIONS: Both instruments have sufficient discriminative validity to
      distinguish between different levels of injection-site pain in adults.

PMID- 11234741
TI  - A case-crossover analysis of a case-control study of alcohol consumption and
      coronary events: the effects of exposure definition and the use of control data.
AB  - BACKGROUND: Case-crossover studies can be used to assess the effects of transient
      exposures in acute events by comparing cases' exposures at the time of the event
      against their usual exposure. Cases from a case-control study can also be
      analysed by this method if appropriate information is obtained. METHODS: We apply
      the case-crossover method to data collected in a case-control study of acute
      coronary events, to estimate the risk of alcohol consumption in the 24 h before a
      coronary event. Two questions, concerning the usual frequency of consuming
      alcohol and how much was consumed, were used in the analysis. The sensitivity of
      effect estimates to the two questions and to different ways of eliciting
      probabilities from them, are examined. The cases and controls were both analysed
      in the same way, assigning controls a 'pseudo-event' time at random. It is
      suggested that controls may provide a benchmark to establish whether bias exists
      in the case-series analysis. RESULTS: We find that the case-crossover analysis is
      sensitive to how exposure probabilities are assigned. Adopting a Poisson model
      for exposures leads to inflated risk estimates. The bias is removed if the
      control series is used to adjust estimates. There appears to be a small
      protective effect from alcohol consumption. CONCLUSION: Case-crossover designs
      have considerable potential, but reliable information on usual exposure limits
      their applicability. More research is required on how best to elicit exposure
      probabilities.

PMID- 11234742
TI  - Activity in prefrontal cortex, not hippocampus, varies parametrically with the
      increasing remoteness of memories.
AB  - The time-scale of hippocampal and neocortical involvement in memory retrieval is
      keenly debated. Using event-related fMRI we examined whether recollecting
      autobiographical and public event memories, ranging from the recent to the very
      remote, was associated with parametric changes in brain activity. A ventrolateral
      prefrontal region was sensitive to memory age, showing increased activation
      during retrieval of recent autobiographical events and subsequent parametric
      decrease with remoteness. While we observed modulation of hippocampal activity in
      relation to memory type (autobiographical events in particular), there was no
      evidence for sensitivity of this region to memory age. These findings are
      concordant with a view of hippocampal involvement in autobiographical memory
      retrieval throughout the lifetime.

PMID- 11234743
TI  - Effects of slow rTMS at the right dorsolateral prefrontal cortex on EEG asymmetry
      and mood.
AB  - In a sham-controlled design (n = 12), slow repetitive transcranial magnetic
      stimulation (rTMS) was applied to the right dorsolateral prefrontal cortex for 20
      min, and the subsequent effects on mood and the EEG spectrum were investigated,
      Analysis revealed a significant left hemisphere increase in EEG theta activity at
      25-35 and 55-65 min after stimulation. In addition, participants reported
      significant decrease in anxiety immediately after stimulation, as well as 35 and
      65 min after rTMS. These findings indicate that reductions in anxiety after slow
      rTMS at the right dorsolateral prefrontal cortex are associated with a
      contralateral increase in theta activity.

PMID- 11234744
TI  - Induction of c-fos in hamster accessory olfactory bulbs by natural and cloned
      aphrodisin.
AB  - Male hamsters were exposed to the female pheromone, aphrodisin (APH), its cloned
      protein backbone (rAPH), and the homologous lipocalin, beta-lactoglobulin (beta
      LG). Of these, only APH elicited mating behavior. Enhanced c-fos protein was
      found in the nuclei of neurons in the accessory olfactory bulb (AOB) after
      exposure to these stimuli. Relative to beta-LG, both rAPH and APH produced
      significant increases in AOB labeling. The modest labeling elicited by rAPH was
      evenly distributed, but the heavier staining elicited by APH was concentrated in
      the caudal region of the AOB. Thus, pheromone receptor neurons in the basal
      compartment of the vomeronasal epithelium, which project to the caudal region of
      the AOB, may respond to APH and provide the input which drives mating behavior.

PMID- 11234745
TI  - Rapid kindling of the hippocampus protects against neural damage resulting from
      status epilepticus.
AB  - It has previously been reported that rats kindled via the standard kindling
      procedure do not exhibit the typical profile of neuropathology following status
      epilepticus. We wished to determine whether a 1-day rapid kindling procedure is
      also neuroprotective against cell damage resulting from prolonged seizure
      activity. We found that rats rapidly kindled from the dorsal hippocampus were
      more resistant to a kainic acid challenge 21-25 days after kindling than were
      unkindled control rats. Kindling prior to a kainic acid challenge also provided
      substantial protection against status epilepticus-induced damage in the CA3
      region of the hippocampus and piriform cortex in most animals. Thus, despite the
      short kindling time period, rapid kindling is neuroprotective against status
      epilepticus-induced cell damage.

PMID- 11234747
TI  - Impairment of predictive saccades in schizophrenia.
AB  - Using infrared oculography, we compared saccades toward predictable and pseudo
      random visual targets in 19 neuroleptic-free patients with schizophrenia
      (including 13 neuroleptic-naive patients) and in 29 age- and gender-matched
      healthy volunteers. Externally driven saccades were not different between
      patients and controls, whether or not the target was predictable. Anticipated
      saccades were specifically less accurate in the patients compared to the
      controls. The difference between primary gain of anticipated and non-anticipated
      saccades was markedly higher in the patients compared to controls (p=0.003).
      These results point to a deficit in the early step of internally driven
      oculomotor planning in schizophrenia.

PMID- 11234746
TI  - Orexin A immunoreactivity and preproorexin mRNA in the brain of Zucker and WKY
      rats.
AB  - The primary role of the orexins was originally believed to be appetite
      regulation, but is now believed to be the regulation of sleep, arousal and
      locomotor activity. Orexin A immunoreactivity (orexin A-IR) and prepro-orexin
      mRNA were measured in the CNS of obese and lean Zucker rats. There were no
      differences in orexin A-IR or prepro-orexin mRNA levels between obese and lean
      Zucker rats. The orexins are therefore unlikely to be important in this model of
      obesity. Levels of orexin A-IR and prepro-orexin mRNA were measured in the CNS of
      Wistar-Kyoto (WKY) rats, which are hypoactive and have abnormal sleep
      architecture. Compared to Wistar rats, WKY rats had significantly lower orexin A
      IR (with differences of up to 100% in some brain regions) and prepro-orexin mRNA
      levels. These observations suggest that the sleep and activity phenotype of the
      WKY strain may be related to orexin deficiency and that this strain may be a
      useful model of partial orexin deficiency.

PMID- 11234748
TI  - Circadian pattern, light responsiveness and localization of rPer1 and rPer2 gene
      expression in the rat retina.
AB  - Circadian expression, light-responsiveness and localization of clock genes, rPer1
      and rPer2, were examined in the rat retina under constant darkness. A significant
      circadian variation was detected in rPer2 transcript levels with a peak at ZT14,
      but not in the rPer1. A light pulse given after constant darkness of 3 days
      increased both rPer1 and rPer2 expression phase-dependently, while rPer1 was
      induced at more times than rPer2. A major site of these gene expression within
      the retina was the inner nuclear layer. These findings indicate that rPer1 and
      rPer2 genes play different roles in the generation and regulation of circadian
      rhythms in the retina from those in the suprachiasmatic nucleus.

PMID- 11234750
TI  - Sodium channel beta1 and beta2 subunits parallel SNS/PN3 alpha-subunit changes in
      injured human sensory neurons.
AB  - Voltage-gated sodium channels consist of a pore-containing alpha-subunit and one
      or more auxiliary beta-subunits, which may modulate channel function. We
      previously demonstrated that sodium channel SNS/PN3 alpha-subunits were decreased
      in human sensory cell bodies after spinal root avulsion injury, and accumulated
      at injured nerve terminals in pain states. Using specific antibodies for
      immunohistochemistry, we have now detected sodium channel beta1 and beta2
      subunits in sensory cell bodies within control human postmortem sensory ganglia
      (78% of small/medium (< or = 50 microm) and 68% of large (> or = 50 microm)
      cells); their changes in cervical sensory ganglia after avulsion injury
      paralleled those described for SNS/PN3 alpha-subunits. Our results suggest that
      alpha- and beta-subunits share common regulatory mechanisms, but present distinct
      targets for novel analgesics.

PMID- 11234749
TI  - Developmental profile of excitatory GABA(A) responses in cultured rat cerebellar
      granule cells.
AB  - GABA induced a transient increase in cytosolic free Ca2+ in cerebellar granule
      cells, which decreased from 3 to 8 days in vitro (DIV). Cytosolic Ca2+ changes
      induced by glutamate/glycine were comparable at 3 and 7 DIV. The GABA response
      was ascribed to GABA(A)-receptor mediated depolarization activating L-type Ca2+
      channels since the response was inhibited by bicuculline or nifedipine. GABA
      mediated Ca2+ rise at 4 DIV was potentiated by pentobarbital or by the
      neurosteroid 5beta-pregnan-3alpha-ol-20-one, or by decreasing the extracellular
      Cl- concentration. Neurons cultured for > 7 DIV showed no rise in intracellular
      Ca2+ in response to GABA regardless of the Cl- gradient. GABA(A) receptor
      mediated cytosolic Ca2+ rise suggests an important role for the excitatory
      activity of GABA in developing cerebellar granule neurons.

PMID- 11234751
TI  - Inhibitory effect of theophylline on recombinant GABA(A) receptor.
AB  - Convulsions due to systemic toxicity are a major and frequently fatal side effect
      of theophylline. The cause of theophylline-induced convulsions is not clear, but
      antagonism of the inhibitory nervous system may be implicated, so we examined the
      effects of theophylline on GABA-induced currents using recombinant GABA(A)
      receptor (GABA(A)-R). Theophylline dose-dependently inhibited GABA-induced
      currents: the IC50 value was 1841+/-63 microM and Hill coefficient 1.09+/-0.03.
      The inhibitory action of theophylline on GABA-induced currents was competitive
      and voltage dependent. The inhibition of GABA-induced currents by theophylline
      may be a primary mechanism underlying theophylline-induced convulsions.

PMID- 11234752
TI  - Plasticity of TTX-sensitive sodium channels PN1 and brain III in injured human
      nerves.
AB  - Sensory neurones co-express voltage-gated sodium channels that mediate TTX
      sensitive (TTX-S) and TTX-resistant (TTX-R) currents, which may contribute to
      chronic pain after nerve injury. We previously demonstrated that TTX-R channels
      were decreased acutely in human sensory cell bodies after central axotomy, but
      accumulated in nerve terminals after peripheral axotomy. We have now studied the
      TTX-S channels PN1 and Brain III, using specific antibodies for
      immunohistochemistry, in dorsal root ganglia (DRG) from 10 patients with
      traumatic central axotomy, nerves from 16 patients with peripheral axotomy, and
      controls. PN1 showed temporal changes similar to the TTX-R channels in sensory
      cell bodies of injured DRG. In contrast, Brain III was found only in injured
      nerves (not control nerves, or control/central axotomy DRG). PNI and Brain III
      are distinct targets for novel analgesics.

PMID- 11234753
TI  - Neural correlates of duplex perception: a whole-head magnetencephalography study.
AB  - Simultaneous experience of the same acoustic stimulus in two distinct
      phenomenological modes, e.g. as a speech-like and as a non-speech event, is
      referred to as duplex perception (DP). The most widely investigated DP paradigm
      splits each of the stop consonant-vowel (CV) syllables /ga/ and /da/ into an
      isolated formant transient (chirp) and the remaining sound structure (base). The
      present study recorded mismatch fields in response to a series of dichotically
      applied base and chirp components using whole-head magnetencephalography (MEG).
      Preattentive mismatch fields showed larger amplitudes in response to
      contralateral deviants. During attention to the fused percept /da/, the left ear
      deviants chirps elicited an enhanced and posteriorly shifted dipole field over
      the ipsilateral hemisphere. These data provide first neurophysiological evidence
      that the integration of acoustic stimulus elements into a coherent syllable
      representation constitutes a distinct stage of left-hemisphere speech sound
      encoding.

PMID- 11234754
TI  - Auditory temporal processing deficit in dyslexia is associated with enhanced
      sensitivity in the visual modality.
AB  - Developmental dyslexia has been associated with a deficit in temporal processing,
      but it is controversial whether the postulated deficit is pansensory or limited
      to the auditory modality. We present psychophysical assessment data of auditory
      and visual temporal processing abilities in children with dyslexia. While none of
      the dyslexic children displayed temporal processing abnormalities in the visual
      sensory modality, dyslexics with poor auditory temporal scores reached high-level
      visual performance. Our results do not confirm the hypothesis of a general
      temporal processing deficit for dyslexia but suggest that limitations in auditory
      temporal processing might be compensated for by a well-functioning visual sensory
      modality.

PMID- 11234755
TI  - BAL modulates glutamate transport in synaptosomes and synaptic vesicles from rat
      brain.
AB  - The therapeutic use of BAL (2,3-dimercaptopropanol) as treatment for poisoning
      has been halted by data suggesting serious neurotoxicity. This article is a
      report on the effects of BAL and other dithiols, DMSA (meso-2,3
      dimercaptosuccinic acid) and DMPS (2,3-dimercaptopropane-1-sulfonic acid), on
      [3H]glutamate release and uptake by rat brain synaptosomes and [3H]glutamate
      uptake by synaptic vesicles. BAL (100 microM) inhibited glutamate uptake (30%)
      and stimulated its basal release (30%) in synaptosomes, without affecting K+
      stimulated release. BAL also inhibited glutamate uptake by synaptic vesicles (up
      to 60%). DMPS and DMSA (100 microM) had no significant effects on these
      parameters. The data reported here provide some evidence of glutamate involvement
      in BAL-induced neurotoxicity by demonstrating direct effects of BAL on
      glutamatergic system modulation.

PMID- 11234756
TI  - Voxel-based morphometric analyses of the brain in children and adolescents
      prenatally exposed to alcohol.
AB  - Children of mothers who abuse alcohol during pregnancy can suffer varying degrees
      of neurological abnormality, cognitive impairment, and behavioral problems, and
      in the worst case, are diagnosed with fetal alcohol syndrome (FAS). The purpose
      of the present study was to localize brain abnormalities in a group of children
      and adolescents prenatally exposed to alcohol using high resolution, 3D
      structural MRI data and whole-brain voxel-based morphometry (VBM). Data were
      collected for 21 children and adolescents with histories of prenatal alcohol
      exposure (ALC) and 21 normally developing individuals. Statistical parametric
      maps revealed abnormalities most prominent in the left hemisphere perisylvian
      cortices of the temporal and parietal lobes where the ALC patients tended to have
      too much gray matter and not enough white matter. These results provide further
      support for dysmorphology in temporo-parietal cortices above and beyond the
      overall microcephaly that results from severe prenatal alcohol exposure.

PMID- 11234757
TI  - Changes in acoustic features and their conjunctions are processed by separate
      neuronal populations.
AB  - We investigated the relationship between the neuronal populations involved in
      detecting change in two acoustic features and their conjunction. Equivalent
      current dipole (ECD) models of the magnetic mismatch negativity (MMNm) generators
      were calculated for infrequent changes in pitch, perceived sound source location,
      and the conjunction of these two features. All of these three changes elicited
      MMNms that were generated in the vicinity of auditory cortex. The location of the
      ECD best describing the MMNm to the conjunction deviant was anterior to those for
      the MMNm responses elicited by either one of the constituent features. The
      present data thus suggest that at least partially separate neuronal populations
      are involved in detecting change in acoustic features and feature conjunctions.

PMID- 11234758
TI  - Hypothalamic orexin-A-immunpositive neurons express Fos in response to central
      glucopenia.
AB  - Reports that glucose antimetabolite treatment elicits hyperphagia and
      hyperglycemia suggest that decreased oxidation of this energy substrate elicits
      compensatory responses that enhance cellular fuel availability. Neurons the
      lateral hypothalamic area (LHA) synthesize the orectic neuropeptide, orexin-A
      (ORX-A). The present study evaluated the functional responsiveness of orexinergic
      neurons to glucopenia by investigating whether these cells express the genomic
      regulatory protein, Fos, in response to glucoprivation. Adult male rats were
      sacrificed 2h after i.p. (400 mg/kg) or intracerebroventricular (i.c.v.; 100
      microg) administration of the antimetabolite, 2-deoxy-D-glucose (2DG) or saline.
      Sections through the LHA, from the level of the paraventricular nucleus (PVN) to
      the posterior hypothalamic area (PHA), were processed by dual-label
      immunocytochemistry for Fos- and OXY-A-immunoreactivity (-ir). Although
      orexinergic neurons expressed negligible Fos-ir following vehicle administration,
      dual-labeled ORX-A neurons were observed in the LHA, as well as the dorsomedial
      hypothalamic nucleus (DMN) and PHA, in both drug-treated groups. Bilateral cell
      counts from representative levels of the LHA, DMN, and PHA showed that in each
      structure, a greater proportion of ORX-A neurons were immunostained for Fos in
      response to systemic than following i.c.v. treatment with 2DG. These results
      provide evidence for the transcriptional activation of hypothalamic ORX-A neurons
      by diminished glucose availability, data that suggest that these cells may
      function within central pathways that govern adaptive responses to deficits of
      this substrate fuel. The findings also support the view that a proportion of this
      phenotypic population is responsive to glucoprivic stimuli of central origin.

PMID- 11234759
TI  - Estrogenic activity of tamoxifen and raloxifene on rat brain AMPA receptors.
AB  - We have previously shown in rats that estradiol has brain regionally specific
      effects on AMPA receptors. The present study investigated hormonal specificity of
      AMPA receptors by comparing the effect of estradiol with tamoxifen or raloxifene,
      which have varying effects on estrogen response in breast, bone and uterus.
      Ovariectomy in rats decreased uterus weight which was restored by estradiol
      treatment, whereas tamoxifen and raloxifene had only a weak effect. Ovariectomy
      left unchanged AMPA receptor specific binding in rat brain whereas estradiol,
      tamoxifen and raloxifene decreased it in cortical and striatal regions of
      ovariectomized rats. Hence, tamoxifen and raloxifene showed agonist estrogenic
      activity on AMPA receptors in specific brain regions, which can be dissociated
      from their antagonist estrogenic activity in the periphery.

PMID- 11234760
TI  - Caspase inhibitors promote the survival of avulsed spinal motoneurons in neonatal
      rats.
AB  - Following ventral root avulsion in neonatal animals, the degeneration of spinal
      motoneurons occurs by an apoptotic-like morphological pathway. In adult animals,
      however, the mechanism of degeneration of injured motoneurons is still
      controversial. Because caspases are important mediators of apoptosis, we have
      investigated the effects of the caspase inhibitors, benzyloxycarbonyl
      Asp(OMe)fluoromethylketone (Boc-D-FMK), and N-acetyl-Asp-Glu-Val-Asp aldehyde (Ac
      DEVD-CHO) on the survival of neonatal and adult spinal motoneurons after root
      avulsion of the C7 spinal cord. In the control neonatal animals, virtually all
      motoneurons had degenerated by 7 days following root avulsion. Treatment with
      either 0.5 microg Boc-D-FMK or 1 microg Ac-DEVD-CHO enhanced the survival of
      motoneurons to 80% and 85% for up to 2 weeks post-injury. By 21 days post-injury,
      70% of avulsed motoneurons were still present after Boc-D-FMK treatment, whereas
      all avulsed motoneurons died after treatment with Ac-DEVD-CHO. In adult animals,
      neither inhibitor was neuroprotective for motoneurons following root avulsion. In
      summary, the inhibition of caspases effectively rescued avulsed neonatal
      motoneurons which are died by apoptotic pathway. By contrast, because caspase
      inhibitors failed to rescue injured motoneurons in adult animals, their death may
      occur by a non-apoptotic pathway.

PMID- 11234761
TI  - Orexinergic innervation of POMC-containing neurons in the rat arcuate nucleus.
AB  - A pre-embedding double immunostaining technique was used to study the synaptic
      relationships between orexin-like immunoreactive axon terminals and
      preopiomelanocortin (POMC)-like immunoreactive neurons in the rat arcuate
      nucleus. Most of the synapses were axo-dendritic, while some axo-somatic synapses
      were also found. Both the axo-somatic and axodendritic synapses were symmetrical.
      In some cases the presynaptic orexin-like immunoreactive axon terminals contained
      a few large dense-cored vesicles. The results suggest that the orexinergic axon
      terminals in the arcuate nucleus may play an important role in the regulation of
      food intake via synapses through POMC neurons.

PMID- 11234762
TI  - Chicken arachnoid granulations: a new model for cerebrospinal fluid absorption in
      man.
AB  - Cerebrospinal fluid (CSF) absorption was investigated chicken and rat using
      infusion tests into the cisterna magna. Data were analysed according to a
      mathematical model by Johnson et al. Results in rat predicted a predominant
      lymphatic mechanism, which was confirmed by rapid outflow of X-ray contrast media
      into the olfactoric mucosa. In contrast, dynamics measurements suggested CSF
      drainage via arachnoid granulations in chicken. CSF spaces along the optic nerve
      were contrasted radiographically resulting in venous drainage. Electron
      microscopically, villus-like structures were found at the distal optic nerve
      connecting the subarachnoid space with accompanying veins, resembling human
      arachnoid granulations. We hypothesize that CSF absorption through arachnoid
      villi in microsmatic chicken reflects the situation in man very well.

PMID- 11234764
TI  - The three dimensional structure of the islands of Calleja: a single heterogenous
      cell complex.
AB  - The islands of Calleja in the rat brain stain brilliantly and stand out clearly
      using the NADPH-diaphorase histochemical staining. The 3-D structure of the
      Islands of Calleja was mapped in sagittal sections of young adult (3 months) and
      aged (28 months) animals. Contours were determined using a camera lucida method,
      and transferred to a computer equipped with an image analyzing system. Alignment
      of the sections using fixed anatomical anchers revealed that the islands of
      Calleja were one continuous structure at both ages studied. The structures varied
      between animals, and there was a pronounced left-right difference in the
      individual rats.

PMID- 11234763
TI  - Adult bone marrow stromal cells administered intravenously to rats after
      traumatic brain injury migrate into brain and improve neurological outcome.
AB  - To measure effect of bone marrow stromal cells (MSCs) administered i.v. on rats
      subjected to traumatic brain injury (TBI), we injected MSCs labeled by BrdU into
      the tail vein 24 h after TBI and sacrificed rats 15 days later. The neurological
      severity score (NSS) and the Rotarod test were used to evaluate neurological
      function. The distribution of the donor cells in brain, heart, lung, kidney,
      liver and spleen were analyzed in recipient rats using immunohistochemical
      staining. MSCs injected i.v. significantly reduced motor and neurological
      deficits compared with control groups by day 15 after TBI. The cells
      preferentially entered and migrated into the parenchyma of the injured brain and
      expressed the neuronal marker NeuN and the astrocytic marker GFAP. MSCs were also
      found in other organs and primarily localized to the vascular structures, without
      any obvious adverse effects. Our data suggest that i.v. administration of MSCs
      may be useful in the treatment of TBI.

PMID- 11234765
TI  - Nicotine regulates alpha7 nicotinic receptor subunit mRNA: implications for
      nicotine dependence.
AB  - Recent evidence suggests that alpha7 subunit-containing nicotinic receptors
      (nAChRs) within the ventral tegmental area (VTA) are involved in the processes
      underlying nicotine tolerance and withdrawal. The current study used in situ
      hybridization histochemistry with multiple radiolabelled probes to amplify mRNA
      signal, to examine the distribution of alpha7 nAChR subunit mRNA both in control
      brains and following chronic nicotine treatment (1.5 and 30.0 mg/kg/day). Low
      levels of alpha7 transcript were detected within substantia nigra pars compacta
      (SNpc), substantia nigra pars reticularis (SNpr) and VTA. Higher levels of alpha7
      transcript were found within the cortex and hippocampus. Following chronic
      nicotine treatment, levels of alpha7 subunit mRNA were significantly elevated in
      SNpc, SNpr and VTA, but were unchanged in cortex and hippocampus.

PMID- 11234766
TI  - Human cortical processing of auditory events over time.
AB  - An essential feature of the human brain is the ability to extract information
      from temporally distributed events in the auditory environment. We addressed this
      temporal encoding ability by modelling how stimulus rate is represented in the
      auditory cortex. We propose that a cortical representation of stimulus rate can
      be achieved through the oscillatory properties of nerve cells. Using non-invasive
      brain measures, we tested the prediction of the model that multiple rebound
      responses (RRs) occur after the ending of stimulation. MEG recordings revealed
      successive RRs which originated in the same areas as the N1s elicited by the
      auditory stimuli at latencies predicted by the model. Our modelling and
      experimental results therefore provide evidence that the temporal structure of
      the auditory environment is decomposed in human auditory cortex by cells
      performing bandpass filtering on periodic input.

PMID- 11234767
TI  - Tissue-specific abolition of Per1 expression in the pars tuberalis by
      pinealectomy in the Syrian hamster.
AB  - Melatonin secretion by the pineal gland transduces photoperiod into a
      neuroendocrine signal. In the pars tuberalis (PT), we have shown that photoperiod
      modifies the amplitude of the clock gene Per1. The aim of this study was to test
      whether the endogenous melatonin signal is required for rhythmic expression of
      Per1 in the PT. Male Syrian hamsters housed in long days (LD, 16:8h light:dark)
      were pinealectomized and Per1 mRNA expression studied by in situ hybridization.
      Pinealectomy abolished the rhythm of Per1 expression in the PT, but had no effect
      on Per1 expression in the suprachiasmatic nucleus (SCN), or the ventromedial
      nucleus (VMH) of the hypothalamus. Interestingly, a single night-time injection
      of melatonin (25 microg), given to pinealectomized animals, failed to restore
      Per1 expression in the PT. These data demonstrate that Per1 expression in the PT
      is driven by melatonin, and that the features of the endogenous signal through
      which the Per1 expression is achieved cannot be reproduced by a single melatonin
      injection.

PMID- 11234768
TI  - Ultrasound activates the auditory cortex of profoundly deaf subjects.
AB  - Using three-dimensional PET, the cortical areas activated by bone-conducted
      ultrasound were measured from five profoundly deaf subjects and compared with the
      cortical areas of normal-hearing subjects activated by stimuli through bone
      conducted ultrasonic, air-conducted, bone-conducted, and vibro-tactile hearing
      aids. All of the hearing aids, including the ultrasonic hearing aid, consistently
      activated the medial portion of the primary auditory cortex of the normal
      volunteers. The same cortical area was also significantly activated in the
      profoundly deaf subjects although the percentage increase in regional cerebral
      blood flow (rCBF) was smaller than in normal subjects. These results suggest that
      extra-cochlear routes convey information to the primary auditory cortex and can
      therefore produce detectable sound sensation even in the profoundly deaf
      subjects, who reported a sensation themselves.

PMID- 11234769
TI  - Fibrillar amyloid beta-protein forms a membrane-like hydrophobic domain.
AB  - Microviscosity of the biological membranes is determined by measuring the
      fluorescence polarization of diphenylhexatriene (DPH). DPH, a hydrophobic probe,
      has negligible fluorescence in the solution. When DPH is incorporated into the
      membrane, it is localized in the membrane hydrophobic core and fluoresces
      strongly. We report here that DPH also fluoresces in the presence of fibrillar
      Abeta (fAbeta). However, it does not fluoresce when it is added to the soluble
      Abeta (sAbeta). DPH inserts into Abeta fibrils in a time-dependent manner, and
      upon centrifugation, it is sedimented along with fibrils. The steady state
      fluorescence polarization of DPH with fAbeta1-40 and fAbeta 1-42 was 0.4592 and
      0.4898 respectively. These results suggest that fAbeta (but not sAbeta) forms a
      hydrophobic domain similar to that of membrane.

PMID- 11234770
TI  - Distribution of GABA(B(1a)), GABA(B(1b)) and GABA(B2) receptor protein in
      cerebral cortex and thalamus of adult rats.
AB  - The distribution of GABA(B) receptor subunits GABA(B(1a)), GABA(B(1b)) and
      GABA(B2), has been examined in the cerebral cortex and thalamus of adult rats
      using an immunocytochemical technique. GABA(B(1a)) and GABA(B(1b)) subunits co
      localized with GABA(B2) in the cortex, where afferent thalamic GABAergic axons
      project to pyramidal neurones. The expression patterns of GABA(B(1a)),
      GABA(B(1b)) and GABA(B2) were similar throughout the thalamus. The data suggest
      that the GABA(B(1b)) subunit might be the presynaptic isoform in the thalamo
      cortical pathway with the GABA(B(1a)) subunit possibly present at postsynaptic
      sites on cell bodies. This contrasts with our previous data, obtained in
      cerebellum and spinal cord which indicate opposite locations. Thus, it seems
      unlikely that functional role along with cellular location can be assigned in a
      general manner to specific GABA(B) receptor subunit splice variants.

PMID- 11234771
TI  - Differential regulation of GABA(A) and GABA(B) receptors during vestibular
      compensation.
AB  - We investigated changes in intrinsic excitability and GABA receptor efficacy in
      rat medial vestibular nucleus (MVN) neurons following 48 h and 7-10 days of
      behavioral recovery after unilateral labyrinthectomy (UL) in the rat. The mean in
      vitro discharge rate of rostral ipsilesional MVN cells at both time points was
      significantly higher than normal, indicating that the intrinsic excitability of
      the deafferented cells undergoes a sustained up-regulation during vestibular
      compensation. In slices from animals that had compensated for 7-10 days after UL,
      the responsiveness of rostral ipsilesional MVN cells to the GABA(A) agonist
      muscimol was not different from normal, while the responsiveness to the GABA(B)
      agonist baclofen was significantly down-regulated. This is in contrast to the
      situation soon after UL, where the efficacy of both GABA(A) and GABA(B) receptors
      is markedly down-regulated. The recovery of fast GABA(A) mediated
      neurotransmission by 7-10 days post-UL presumably enables ipsilesional cells to
      again respond to vestibular stimulation, through commissural inhibitory
      modulation from the intact side. The permanent loss of excitatory input from the
      lesioned side may be, in effect, counteracted by the long-term down-regulation of
      slow GABA(B) receptors in the de-afferented neurons.

PMID- 11234772
TI  - Monocyte chemoattractant protein (MCP)-1 is rapidly expressed by sympathetic
      ganglion neurons following axonal injury.
AB  - EDI-immunoreactive macrophages, absent from the superior cervical ganglia (SCG)
      of normal rats, appear in these ganglia within 48h after postganglionic axotomy.
      Further, resident macrophages show changes after axotomy. Since chemokines
      function as chemoattractants and activators of leukocytes, the effects of axotomy
      on chemokine expression in the SCG were examined. Within 6 h after nerve
      transection, increases were seen in mRNA levels for monocyte chemoattractant
      protein (MCP)-1. MCP-1 mRNA was concentrated in a population of neurons, while
      MCP-1 protein was localized to endothelial cells. This axotomy-induced neuronal
      MCP-1 expression may trigger the infiltration and/or activation of macrophages in
      SCG after injury.

PMID- 11234773
TI  - Vesicle-associated proteins and transmitter release from sympathetic ganglionic
      boutons.
AB  - A method is reported for introducing peptides derived from SNARE proteins that
      control exocytosis of vesicles at boutons formed by sympathetic ganglion cells in
      tissue culture. These peptides were coupled to the DNA binding domain of the
      Drosophila transcription factor antennapedia, called penetratin. This facilitated
      the passage of peptides across the bouton membrane. FM1-43 was used to monitor
      the exocytosis of transmitter from depolarized boutons after their exposure to
      the penetratin-peptide sequences IETRHNEIIKLETSIRELHD of syntaxin and
      KGFLSSLFGGSSK of alpha-SNAP, both of which blocked secretion, whereas the peptide
      sequences SELDDRA-DALQAGASQFETSAAKLKRK of synaptobrevin did not. This report
      introduces a readily applicable method for determining the effect of different
      peptide sequences of vesicle-associated proteins on secretion at vertebrate
      boutons and presents an account of the effects of a selection of such peptides on
      exocytosis.

PMID- 11234774
TI  - GT1b ganglioside induces death of dopaminergic neurons in rat mesencephalic
      cultures.
AB  - We examined neurotoxicity of GT1b against dopaminergic neurons in vitro. Cultures
      of mesencephalic cells deprived of serum underwent the loss of 19% of tyrosine
      hydroxylase immunopositive (TH-ip) neurons. In cultures deprived of serum,
      treatment with 10-30 microg/ml GT1b attenuated the number of TH-ip neurons by 26
      69%, respectively, compared to non-treated cultures. Intriguingly, cultures
      deprived of serum were more vulnerable to GT1b-induced neurotoxicity. Application
      of 60 microg/ml GT1b to cultures grown in serum containing media resulted in the
      loss of 26% of TH-ip neurons, similar to that (28%) observed in serum-deprived
      cultures treated with 10 microg/ml GT1b. Moreover, in our cultures, absence of
      nitric oxide (NO) production after GT1b treatment was obvious. The present
      results strongly suggest direct neurotoxic actions of GT1b against dopaminergic
      neurons regardless of NO.

PMID- 11234775
TI  - Protective effects of pamiteplase, a modified t-PA, in a rat model of embolic
      stroke.
AB  - The effects of alteplase (tissue plasminogen activator, t-PA) and pamiteplase (a
      modified t-PA with longer half-life and increased potency) were compared in a
      clinically relevant model of embolic stroke. Rats were treated with pamiteplase
      (0.5 mg/kg or 1 mg/kg bolus), alteplase (10 mg/kg infusion) or normal saline.
      Pamiteplase (1 mg/kg) was as effective as alteplase in reducing 24 h brain
      infarct volumes, neurological deficit scores and residual clot grades. Cerebral
      blood flow recovery at 30 min after thrombolytic treatment was partial and did
      not correlate with 24 h infarct volumes or neurological deficits. However, there
      was good correlation between 24 h residual clot grades and infarct volumes,
      suggesting a delayed timeframe for pamiteplase- and alteplase-induced
      reperfusion.

PMID- 11234776
TI  - Scopolamine reduces the P35m and P60m deflections of the human somatosensory
      evoked magnetic fields.
AB  - Acetylcholine (ACh) is a potent neuromodulator in the brain with multiple,
      complex effects on neuronal function, most of which are mediated by muscarinic
      receptors. Generally, the most significant effect is excitation of pyramidal
      neurones and facilitation of responses to afferent stimulation. Much of the
      information on the ACh effects comes from studies utilizing in vitro or
      anesthetized in vivo preparations, while fewer data are available from awake
      animals or humans. We studied human somatosensory evoked magnetic fields (SEFs),
      which reflect summated postsynaptic currents in pyramidal neurones in area 3b,
      and in the opercular somatosensory cortex, when cholinergic transmission was
      modulated either by a central (scopolamine, 0.3 mg, i.v.) or peripheral
      (glycopyrrolate, 0.2 mg, i.v.) muscarinic antagonist. A randomized, double-blind,
      cross-over design was employed. SEFs were elicited by right median nerve
      stimulation at the wrist with constant-current pulses above motor threshold. The
      first excitatory cortical response from area 3b (N20m) was not affected by the
      central muscarinic blockade, while later P35m and P60m deflections were
      significantly reduced. The responses from the opercular somatosensory cortex
      showed some tendency toward reduction, but no significant alterations. The
      results show that somatosensory cortical processing can be modulated by
      muscarinic transmission at a relatively early stage. Relative membrane
      hyperpolarization of pyramidal neurons due to scopolamine (caused by blocking an
      ACh-induced tonic depolarization) is discussed as a possible mechanism underlying
      the observed effects.

PMID- 11234777
TI  - Cloning of the mouse dysferlin gene and genomic characterization of the SJL-Dysf
      mutation.
AB  - The SJL mouse strain has been widely used as an animal model for experimental
      autoimmune encephalitis (EAE), inflammatory muscle disease and lymphomas and has
      also been used as a background strain for the generation of animal models for a
      variety of diseases including motor neurone disease, multiple sclerosis and
      atherosclerosis. Recently the SJL mouse was shown to have myopathy due to
      dysferlin deficiency, so that it can now be considered a natural animal model for
      limb-girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy (MM). We
      have cloned the mouse dysferlin cDNA and analysis of the sequence shows that the
      mouse dysferlin gene is characterized by six C2 domain sequences and a C-terminal
      anchoring domain, with the human and the mouse dysferlin genes sharing > 90%
      sequence homology overall. Genomic analysis of the SJL mutation confirms that the
      171 bp RNA deletion has arisen by exon skipping resulting from a splice site
      mutation. The identification of this mutation has implications for the various
      groups using this widely available mouse stock.

PMID- 11234778
TI  - The BACE gene: genomic structure and candidate gene study in late-onset
      Alzheimer's disease.
AB  - Alzheimer's disease (AD) pathology is characterized by beta-amyloid plaques and
      neurofibrillary tangles. Studies of autosomal dominant early-onset AD mutations
      suggest that beta-amyloid overproduction is sufficient to cause AD. Recently, the
      BACE gene, which encodes beta-secretase, the rate limiting enzyme in beta-amyloid
      formation, has been identified. Since this gene is a strong candidate gene for
      late-onset AD because of its function, we have characterized its genomic
      organization and identified two polymorphisms. Neither of these polymorphisms
      were associated with AD risk in genetic association studies comparing autopsy
      confirmed late-onset AD cases and age-matched non-demented controls. Thus, we
      find no evidence that this locus influences risk for late-onset AD.

PMID- 11234779
TI  - Input-specific LTP and depotentiation in the basolateral amygdala.
AB  - The amygdala plays a central role in emotional memory. The cellular mechanisms by
      which the amygdala participates in emotional learning are believed to be changes
      in efficacy of synaptic transmission, similar to long-term potentiation (LTP) and
      long-term depression (LTD). Although different forms of LTP have been shown in
      the amygdala, many of their features are still unknown. Here, we use both field
      potential and intracellular recordings in rat amygdala slices, and show that LTP
      in the basolateral nucleus, induced by high-frequency stimulation (HFS) of the
      external capsule is input-specific, can be reversed by low-frequency stimulation
      (LFS), and can be reinstated by HFS. These synapse-specific, reversible changes
      in synaptic strength in the basolateral nucleus of the amygdala may be important
      to amygdala's role in emotional memory.

PMID- 11234780
TI  - Nicotine facilitates noradrenaline release in the rat supraoptic nucleus.
AB  - Nicotine injected in the supraoptic nucleus facilitates vasopressin release from
      the neurohypophysis. Nicotinic acetylcholine receptors have been found not only
      on vasopressin-producing cell bodies but also on presynaptic nerve terminals in
      the nucleus. Vasopressin cells receive excitatory synaptic inputs from
      noradrenergic neurones. To test whether nicotine facilitates noradrenaline
      release in the supraoptic nucleus, we perfused the supraoptic nucleus with
      nicotine through a microdialysis probe. Nicotine increased the extracellular
      noradrenaline concentrations in the nucleus. A noradrenaline uptake inhibitor,
      desipramine, increased the extracellular noradrenaline concentrations in the
      nucleus and did not block the noradrenaline increase after nicotine. The results
      suggest that nicotine acts within the supraoptic nucleus to facilitate
      noradrenaline release pre-synaptically. This presynaptic action may contribute,
      in part, to vasopressin release after nicotine.

PMID- 11234781
TI  - Postsynaptic K+ current induced by nociceptin in medullary dorsal horn neurons.
AB  - The actions of the endogenous ORL1 receptor (opioid receptor-like1) ligand
      nociceptin on the membrane properties of rat trigeminal nucleus caudalis neurons
      were examined by use of whole cell and perforated patch clamp recording in brain
      slices. Nociceptin produced an outward current in all neurons tested (EC50 112
      nM). The outward current produced by nociceptin was completely reversed with the
      addition of the non-peptide ORL1 antagonist J-113397. Outward currents reversed
      polarity at -99+/-2 mV, close to the potential for K+ of -102 mV, suggesting that
      they were mediated by an increased K+ conductance. These results suggest that the
      analgesic action of nociceptin might be mediated by direct postsynaptic
      inhibition within the dorsal horn.

PMID- 11234782
TI  - Mechanisms of depression of transmitter release at synapses.

PMID- 11234783
TI  - Efficacy of patient-delivered partner medication in the treatment of sexual
      partners in Uganda.
AB  - BACKGROUND: Patient-based partner referral (PBPR), which is the main method for
      treating sexual partners of patients with sexually transmitted diseases (STDs),
      has limited effectiveness. GOAL: The authors compared the efficacy of PBPR with
      patient-delivered partner medication (PDPM) among patients attending the Mulago
      STD clinic in Kampala, Uganda. STUDY DESIGN: A total of 383 patients (187 women,
      196 men) with STDs were randomized to the PBPR or PDPM group. The proportion of
      sexual partners treated in either group was compared using the chi-square
      statistic by intention to treat for partners whose follow-up status was unknown.
      RESULTS: The two groups had similar background characteristics. Of the 237
      partners elicited, 176 (74%) were reported treated in the PDPM group. In the PBPR
      group, in which 234 partners were elicited, 79 (34%) were referred to the
      treatment clinic. This difference was statistically significant (risk ratio [RR],
      2.44; 95% CI, 1.95-3.07; P < 0.001). Furthermore, PDPM was more effective than
      PBPR for women and for casual partners for whom PBPR is considered difficult. For
      women, 86 of 103 partners in the PDPM group were reported treated, compared with
      23 of 104 partners in the PBPR group (RR, 4.55; 95% CI, 2.92-7.08; P < 0.001).
      For casual partners, 18 of 51 (34%) were reported treated in the PDPM group,
      compared with only three of 45 partners (7%) who were referred in the PBPR group
      (RR, 1.43; 95% CI, 1.40-2.65; P < 0.01). CONCLUSION: Patient-delivered partner
      medication is more effective than patient-based partner referral in the treatment
      of sexual partners.

PMID- 11234784
TI  - Epidemiology of the reemergence of gonorrhea in Sweden.
AB  - BACKGROUND: After many years of decline, the incidence of gonorrhea in Sweden
      reached an all-time low of 2.4 cases per 100,000 inhabitants in 1996; however,
      the incidence has been increasing since 1997. GOAL: To describe the reemergence
      of gonorrhea in Sweden using clinical epidemiologic data and microbiologic
      characterization of isolated strains of Neisseria gonorrhoeae. STUDY DESIGN: N
      gonorrhoeae strains isolated in Sweden from February 1998 to January 1999 were
      serotyped and an epidemiologic data questionnaire was sent to each clinician
      reporting a case of gonorrhea. RESULTS: Epidemiologic and microbiologic data were
      obtained for 357 cases (91% of all cases diagnosed during the period). Domestic
      cases had significantly increased since 1997. Serovar IB-3 was the most common
      isolate in domestic cases of heterosexually exposed teenagers, and serovar IB-2
      was the most frequent isolate in domestic cases of homosexually exposed men. Of
      the imported cases, 47% were exposed in Asia and 6.5% were exposed in Eastern
      Europe. CONCLUSION: The increase of gonorrhea in Sweden is due to an increase of
      domestic cases. Heterosexual teenagers and homosexual men were identified as core
      groups infected by different serovars of N gonorrhoeae.

PMID- 11234785
TI  - Prevalence of 5-nitroimidazole-resistant trichomonas vaginalis in Oviedo, Spain.

PMID- 11234786
TI  - Determinants of persistent and recurrent Chlamydia trachomatis infection in young
      women: results of a multicenter cohort study.
AB  - BACKGROUND: Sequelae of genital Chlamydia trachomatis infection in women are more
      strongly linked to repeat infections than to initial ones, and persistent or
      subsequent infections foster continued transmission. OBJECTIVE: To identify
      factors associated with persistent and recurrent chlamydial infection in young
      women that might influence prevention strategies. METHODS: Teenage and young
      adult women with uncomplicated C trachomatis infection attending reproductive
      health, sexually transmitted disease, and adolescent medicine clinics in five US
      cities were recruited to a cohort study. Persistent or recurrent chlamydial
      infection was detected by ligase chain reaction (LCR) testing of urine 1 month
      and 4 months after treatment. RESULTS: Among 1,194 women treated for chlamydial
      infection, 792 (66.4%) returned for the first follow-up visit, 50 (6.3 %) of whom
      had positive LCR results. At that visit, women who resumed sex since treatment
      were more likely to have chlamydial infection (relative risk [RR], 2.0; 95% CI,
      1.03-3.9), as were those who did not complete treatment (RR, 3.4; 95% CI, 1.6
      7.3). Among women who tested negative for C trachomatis at the first follow-up
      visit, 36 (7.1%) of 505 had positive results by LCR at the second follow-up
      visit. Reinfection at this visit was not clearly associated with having a new sex
      partner or other sexual behavior risks; new infection was likely due to
      resumption of sex with untreated partners. Overall, 13.4% of women had persistent
      infection or became reinfected after a median of 4.3 months, a rate of 33
      infections per 1,000 person months. CONCLUSIONS: Persistent or recurrent
      infection is very common in young women with chlamydial infection. Improved
      strategies are needed to assure treatment of women's male sex partners.
      Rescreening, or retesting of women for chlamydial infection a few months after
      treatment, also is recommended as a routine chlamydia prevention strategy.

PMID- 11234787
TI  - How a net works: implications of network structure for the persistence and
      control of sexually transmitted diseases and HIV.

PMID- 11234788
TI  - Social context of sexual relationships among rural African Americans.
AB  - BACKGROUND: Reasons for the strikingly increased rates of HIV and other sexually
      transmitted infections (STIs) among African Americans in the rural Southeastern
      United States remain unclear. Investigators have devoted little attention to the
      potential influence of the social and economic context on sexual behaviors. GOAL:
      To examine the potential influence of these contextual factors on behaviors that
      promote the transmission of STIs. STUDY DESIGN: Focus group interviews in which
      African Americans from rural North Carolina discussed life in their communities
      and contextual factors affecting sexual behavior. RESULTS: Respondents reported
      pervasive economic and racial oppression, lack of community recreation, boredom,
      and resultant substance abuse. Many perceived a shortage of black men because of
      their higher mortality and incarceration rates compared with whites, and believed
      this male shortage to be partly responsible for the concurrent sexual
      partnerships that they perceived as widespread among unmarried persons.
      CONCLUSION: Contextual features including racism, discrimination, limited
      employment opportunity, and resultant economic and social inequity may promote
      sexual patterns that transmit STIs.

PMID- 11234789
TI  - Prevalence of Kaposi sarcoma-associated herpesvirus compared with selected
      sexually transmitted diseases in adolescents and young adults in rural Rakai
      District, Uganda.
AB  - BACKGROUND: Kaposi sarcoma-associated herpesvirus (KSHV) is transmitted by routes
      such as homosexual intercourse and is associated with HIV infection in
      industrialized countries. However, there is little information about its
      transmission in developing countries where Kaposi sarcoma is an endemic disease.
      GOAL: To examine KSHV seroprevalence in young adults in a general, rural Ugandan
      population, and to compare this prevalence with rates of known sexually
      transmitted infections. STUDY DESIGN: The seroprevalence of KSHV was compared
      with the epidemiology of sexually transmitted diseases in 523 sexually active
      subjects aged 15 to 29 years who were randomly selected from a general population
      cohort in rural Rakai District, Uganda. Participants provided in-home interview
      data and specimens. Sera were tested for KSHV using immunofluorescence assay and
      immunoblot for lytically expressed recombinant KSHV ORF65.2. Sera were also
      tested for HIV type 1, herpes simplex virus type 2, and syphilis. RESULTS: The
      prevalence of KSHV was significantly higher in participants 15 to 19 years
      compared with older persons 25 to 29 years (45.0% and 36.1%, respectively;
      adjusted odds ratio, 0.48; 95% CI, 0.28-0.82). In contrast, herpes simplex virus
      type 2 and HIV type 1 prevalence increased with age. Kaposi sarcoma-associated
      herpesvirus serostatus was not associated with HIV type 1, syphilis, herpes
      simplex virus type 2, or number of sexual partners. Homosexual and anal
      intercourse were reported by less than 1% of participants. CONCLUSIONS: Kaposi
      sarcoma-associated herpesvirus does not appear to be a heterosexually transmitted
      infection in rural Uganda.

PMID- 11234790
TI  - Neisseria gonorrhoeae resistant to ciprofloxacin: first report in Cuba.
AB  - BACKGROUND AND OBJECTIVES: The Cuban Ministry of Public Health plans to implement
      the syndromic approach to sexually transmitted diseases in persons with urethral
      or vaginal syndrome in Cuba using 500 mg ciprofloxacin as therapy. Although the
      emergence of clinical isolates of Neisseria gonorrhoeae with decreased
      susceptibility to ciprofloxacin have been sporadically detected in Cuba, there
      has been no report of isolates that exhibited significant resistance to this
      drug. This is the first report of the isolation of a N gonorrhoeae strain
      resistant to ciprofloxacin in Cuba. STUDY DESIGN: Case report. CONCLUSIONS: This
      case emphasizes the need for awareness regarding the potential emergence of a
      clinically significant resistance of N gonorrhoeae in Cuba. There is a need for
      continued antimicrobial susceptibility surveillance of Cuban isolates to
      ciprofloxacin and other fluoroquinolones.

PMID- 11234791
TI  - Enhanced efficiency of female-to-male HIV transmission in core groups in
      developing countries: the need to target men.
AB  - BACKGROUND: The spread of heterosexual HIV in developing countries is
      heterogeneous. Factors that explain the wide diversity of HIV prevalences in
      different countries are undetermined. International aid organizations currently
      appear to be focusing activities mainly on women rather than on men. GOAL: To
      identify critical determinants contributing to the high rates of heterosexual HIV
      transmission in developing countries through a review of studies investigating
      HIV per-act transmission rates, and to discuss how these factors might be
      prioritized through HIV-prevention interventions. STUDY DESIGN: Studies
      investigating the per-act HIV transmission rate were identified through a MEDLINE
      search and a review of the abstracts of the Annual International AIDS
      Conferences. RESULTS: When the summary mean per-act HIV transmission rates were
      calculated, the ratio of female-to-male HIV transmission in developing countries
      compared with that in the developed world was 341, whereas that for male-to
      female transmission was 2.9. CONCLUSION: Enhanced female-to-male HIV transmission
      in male core groups is a critical determinant of high-prevalence HIV epidemics
      among heterosexuals in developing countries. In addition to condom promotion,
      there is a need for an increased emphasis on HIV-prevention activities in men to
      decrease their susceptibility in developing countries, particularly in the
      countries most affected by the epidemic.

PMID- 11234792
TI  - Missed opportunities for congenital syphilis prevention in an urban southeastern
      hospital.
AB  - BACKGROUND: Despite recent declines in syphilis rates nationally, recent
      outbreaks suggest that prevention of congenital syphilis remains an ongoing
      public health problem. GOALS: To identify missed opportunities for congenital
      syphilis prevention during prenatal care. STUDY DESIGN: Retrospective medical
      record review of 157 live birth or stillbirth deliveries that involved cases of
      congenital syphilis from Grady Memorial Hospital (Atlanta, GA). RESULTS: The
      hospital congenital syphilis prevalence was 8.2 cases per 1,000 live births. Six
      percent of case patients were HIV positive. Opportunities for earlier maternal
      screening, treatment, or diagnosis were missed in 60% of case patients who
      received timely prenatal care. Congenital syphilis cases attributable to
      preventable missed opportunities were significantly more common among case
      patients with fewer prenatal visits (66% versus 28%, P = 0.01). CONCLUSION:
      Provider efforts to reduce congenital syphilis in high-risk populations receiving
      prenatal care should focus on (1) screening patients at the first opportunity, at
      both the first prenatal visit and during the third trimester (i.e., 28 weeks);
      (2) performing on-site testing and same-day treatment; (3) providing appropriate
      treatment to infected women with penicillin allergy; (4) referring sex partners
      for treatment to prevent reinfection; and (5) screening all pregnant women
      attending emergency clinics.

PMID- 11234793
TI  - Use of a glycoprotein G-based type-specific assay to detect antibodies to herpes
      simplex virus type 2 among persons attending sexually transmitted disease
      clinics.
AB  - BACKGROUND: Most genital herpes simplex virus type 2 (HSV-2) infections are
      unrecognized, thus, strategies to reduce the sexual transmission of HSV-2 are
      partly dependent on serologic screening. GOAL: To define performance
      characteristics of the Gull/ Meridian glycoprotein G-based HSV-2 enzyme-linked
      immunosorbent assay among sexually transmitted disease clinic attendees and
      correlates of test acceptance. STUDY DESIGN: The cross-sectional study was
      conducted during two periods. Serologic testing was offered at a US $15 charge
      during the first period and at no charge during the second period. Sera were
      tested by a type-specific glycoprotein G enzyme-linked immunosorbent assay and
      Western blot analysis, with the latter test used as the reference standard.
      RESULTS: Acceptance of HSV-2 testing was associated with free testing (odds
      ratio, 7.5; 95% CI, 6.0-9.9), older age, and white race. Sensitivity of the HSV-2
      assay was 80.5% and specificity was 98.5%. The HSV-2 positive and negative
      predictive values were 95.8% (95% CI, 91.6-98.0%) and 92.2% (95 % CI, 89.6 
      94.2%), respectively. Antibodies to HSV-2 were detected in 25.9% of 606 persons
      with no history of genital herpes. CONCLUSION: Acceptance of HSV-2 serologic
      testing was cost sensitive. In this high-prevalence population, the positive
      predictive value of the enzyme-linked immunosorbent assay was sufficient to
      warrant its use without a confirmatory test. This assay could be useful in the
      screening of sexually active adults to detect unrecognized HSV-2 infection.

PMID- 11234794
TI  - Voltammetric determination of benazepril and ramipril in dosage forms and
      biological fluids through nitrosation.
AB  - A simple and highly sensitive voltammetric method was developed for the
      determination of benazepril (I) and ramipril (II). The compounds were treated
      with nitrous acid, and the cathodic current produced by the resulting nitroso
      derivatives was measured. The voltammetric behavior was studied by adopting
      direct current (DCt), differential pulse (DPP), and alternating current (ACt)
      polarography. Both compounds produced well-defined, diffusion-controlled cathodic
      waves over the whole pH range in Britton-Robinson buffers (BRb). At pH 3 and 5,
      the values of diffusion-current constants (Id), were 5.90 +/- 0.40 and 6.66 +/-
      0.61 for I and II, respectively. The current concentration plots for I were
      rectilinear over the range of 1.5-40 and 0.1-30 microg/mL in the DCt and DPP
      modes, respectively; for II, the range was 2-30 and 0.1-20 microg/mL in the DCt
      and DPP modes, respectively. The minimum detectabilities (S/N = 2) were 0.015
      microg/mL (about 3.25 x 10(-8)M) and 0.012 microg/mL (about 2.88 x 10(-8)M) for I
      and II, respectively, adopting the DPP mode. Results obtained for the proposed
      method when applied to the determination of both compounds in dosage forms were
      in good agreement with those obtained using reference methods.
      Hydrochlorthiazide, which is frequently co-formulated with these drugs, did not
      interfere with the assay. The method was also applied to the determination of
      benazepril in spiked human urine and plasma. The percentage recoveries adopting
      the DPP mode were 96.2 +/- 1.21 and 95.7 +/- 1.61, respectively.

PMID- 11234795
TI  - Determination of the efficacy of preservation of non-eye area water-miscible
      cosmetic and toiletry formulations: collaborative study.
AB  - A collaborative study was conducted to test a method developed to distinguish
      between adequately and inadequately preserved cosmetic formulations. Nineteen
      laboratories participated in the study. Samples tested included shampoos, hair
      conditioners, oil-in-water emulsions, and water-in-oil-emulsions. Triplicate
      samples of 4 adequately preserved and 4 inadequately preserved cosmetic products
      were tested by each collaborative laboratory. Results showed that all
      inadequately preserved shampoo and conditioner samples failed to meet the
      acceptance criteria for adequately preserved formulations. Of the 51 preserved
      samples, 49 shampoos and 48 conditioners met the criteria for adequate
      preservation. All samples of inadequately preserved water-in-oil emulsions and
      oil-in-water emulsions failed to meet the acceptance criteria, whereas all
      adequately preserved emulsion formulations met the acceptance criteria.

PMID- 11234797
TI  - Automated microwave digestion of certifiable color additives for determination of
      mercury by cold vapor atomic absorption spectrometry.
AB  - A procedure using an automated microwave flow digestion technique was developed
      and validated for the digestion of samples of certifiable color additives before
      mercury determination by cold vapor atomic absorption spectrometry. Recovery
      studies were performed by spiking most of the color additives subject to batch
      certification by the U.S. Food and Drug Administration with inorganic mercury
      (HgNO3) and with organic mercury (CH3HgCl). Successful recoveries of 72-113% Hg
      added at the 1 microg/g level were obtained. A method detection limit of 0.2
      microg Hg/g was estimated from a Hg-spiked FD&C Yellow No. 6 sample. At the
      specification level of 1 ppm Hg (1 microg Hg/g), the 95% confidence interval was
      +/- 0.2 ppm (0.2 microg Hg/g).

PMID- 11234796
TI  - Electroanalytical determination of cadmium and lead in deciduous teeth after
      microwave oven digestion.
AB  - A method using differential pulse anodic stripping voltammetry after microwave
      oven digestion was developed for the simultaneous determination of Cd(II) and
      Pb(II) in the deciduous teeth of children. Each tooth was weighed; deposited in a
      120 mL capped Teflon vessel with 5 mL 65% nitric acid, Suprapur analytical grade;
      and digested in a 2-step microwave oven for 15 min. The detection limits for
      Cd(II) and Pb(II) in the final solution were 0.078 and 0.323 microg/L, and the
      quantitation limits 0.394 and 1.613 microg/L, respectively, with a linearity
      range of 2 microg/L for Cd(II) and 23.3 microg/L for Pb(II). The sensitivity was
      2.51 nA/microg-L and 1.37 nA/microg-L, for Cd(II) and Pb(II). The main advantages
      of this technique are a complete and satisfactory dissolution of the tooth
      material with the proposed microwave oven digestion procedure, without sample
      pretreatments, such as drying, ashing, or powdering. The voltammetric procedure
      proved to be well designed because of significant goodness of fit to a linear
      model, and the accuracy of the method was established as compared with standard
      reference material. The methodology has enabled us to study Cd(II) and Pb(II) in
      371 deciduous teeth from school children in Cartagena, Spain.

PMID- 11234798
TI  - Immunochemical applications in environmental science.
AB  - Immunochemical methods are based on selective antibodies combining with a
      particular target analyte or analyte group. The specific binding between antibody
      and analyte can be used to detect environmental contaminants in a variety of
      sample matrixes. Immunoassay methods provide cost-effective, sensitive, and
      selective analyses for many compounds of environmental and human health concern.
      Immunoaffinity chromatography methods have been integrated with chromatographic
      methods and are also being used as efficient sample preparations prior to
      immunochemical or instrumental detection. Immunosensors show promise in obtaining
      rapid online analyses. These and other advancements in immunochemical methods
      continue the expansion of their role from field screening methods to highly
      quantitative procedures that can be easily integrated into the environmental
      analytical laboratory.

PMID- 11234799
TI  - Determination of phenylephrine hydrochloride by flow injection analysis with
      chemiluminescence detection.
AB  - A new method is proposed for the determination of phenylephrine hydrochloride by
      flow injection analysis with direct chemiluminescence detection. The method is
      based on the oxidation of the drug by potassium permanganate in sulfuric acid
      medium at 80 degrees C. The calibration graph is linear over the range 0.03-8 ppm
      phenylephrine hydrochloride, with a relative standard deviation (n = 51, 0.5 ppm)
      of 1.1% and sample throughput of 134/h. The influence of 38 different foreign
      compounds was tested, and the method was applied to the determination of
      phenylephrine hydrochloride in 8 different pharmaceutical formulations.

PMID- 11234800
TI  - Analysis of DDT residues in soil by ELISA: an international interlaboratory
      study.
AB  - An international interlaboratory study was conducted to determine the performance
      of a group of laboratories from developing and developed countries. The study
      used a commercial microwell ELISA on unknown samples spiked with different levels
      of DDT. The study design was based on Youden pairs and balanced replicates. Two
      soils, differing in particle size distributions, organic matter content, and
      cation-exchange capacities and thought to be DDT-free, were spiked at 5 DDT
      levels between 0.025 and 2 mg/kg. Nineteen laboratories in 17 countries took part
      in the collaborative trial; of these, the majority were modestly equipped
      laboratories in developing countries. Samples were analyzed without filtration or
      cleanup and using standards of pure DDT in methanol. Data were analyzed for
      repeatability and reproducibility, and average recoveries at the spike levels
      were calculated. Mean real recoveries for both soils were similar (103% for soil
      A and 100% for soil B), with values between 0.1 and 2 mg/kg DDT. Precision
      estimates were best in the linear working range of the assay (0.1-0.5 mg/kg DDT),
      with reproducibility relative standard deviations (RSDR) typically averaging
      about 38 and 46% near the upper and lower detection limits, respectively.
      Corresponding repeatability relative standard deviation (RSDr) values were 20-36%
      and 36-57%. Thus, even though much of the trial was performed under developing
      country conditions, performance statistics were similar to other reported results
      obtained with ELISAs on small molecules of agricultural importance, such as
      mycotoxins and pesticide and antibiotic residues.

PMID- 11234801
TI  - Polyclonal-based ELISA for the identification of cyclohexanedione analogs that
      inhibit maize acetyl coenzyme-A carboxylase.
AB  - Cyclohexanedione herbicides inhibit monocotyledonous acetyl coenzyme-A
      carboxylase (ACCase; E.C. 6.4.1.2.), which catalyzes the first committed step in
      fatty acid biosynthesis. Although the target site has been identified, little is
      known about the mechanisms involved in herbicide binding. An immunological study
      was undertaken to create a model to better characterize the herbicide-enzyme
      interaction. Cyclohexanedione-specific antiserum was raised in New Zealand white
      rabbits by immunizing them with a cyclohexanedione analog-bovine serum albumin
      conjugate. Two indirect enzyme-linked immunosorbent assays (ELISA) were developed
      using 2 different cyclohexanedione analogs conjugated to ovalbumin as coating
      conjugates. Nineteen cyclohexanedione analogs, 13 active ACCase inhibitors, and 6
      inactive analogs were tested for their ability to compete with both coating
      conjugates for antiserum binding. All active ACCase inhibitors were observed to
      compete with both coating conjugates, whereas all inactive analogs failed to
      compete with at least one coating conjugate. On the basis of these results, the
      immunological model could be used to distinguish all active ACCase inhibitors
      from inactive analogs using the 2 ELISAs sequentially.

PMID- 11234802
TI  - Long-term monitoring of atrazine contamination in soil by ELISA.
AB  - An enzyme-linked immunoassay (ELISA) was used for screening atrazine residues in
      soil. Samples were annually collected in Southern Germany between 1993 and 1998.
      An average of 419.5 samples was analyzed per year amounting to 2517 samples. The
      fraction of positive samples defined by atrazine concentrations >100 microg/kg
      soil decreased successively from 8% (corresponding to 33 samples) in 1993 to 0.6%
      (corresponding to 2 samples) in 1998. All positive samples and a selection of
      negative samples were subsequently validated by HPLC. Comparison of ELISA and
      HPLC data yielded correlation coefficient values of r = 0.958-0.981 (n = 18-47),
      except for 1995 when only a correlation of r = 0.864 (n = 18) was obtained. Four
      samples were overestimated and another 4 were underestimated with respect to the
      atrazine threshold value of 100 microg/kg soil as revealed by HPLC validation.
      Thus, 99.68% of 2,517 analyzed samples were correctly evaluated. The precision
      and reproducibility of the ELISA were adequate for a prescreening tool. The low
      cost per sample and the high sample throughput are not yet achievable by
      conventional analytical methods. The described combination of ELISA and HPLC has
      the potential to take advantage of both methods and to restrict determination
      errors to a minimum.

PMID- 11234804
TI  - Detection of pesticides and pesticide metabolites using the cross reactivity of
      enzyme immunoassays.
AB  - Enzyme immunoassay is an important environmental analysis method that may be used
      to identify many pesticide analytes in water samples. Because of similarities in
      chemical structure between various members of a pesticide class, there often may
      be an unwanted response that is characterized by a percentage of cross
      reactivity. Also, there may be cross reactivity caused by degradation products of
      the target analyte that may be present in the sample. In this paper, the concept
      of cross reactivity caused by degradation products or by nontarget analytes is
      explored as a tool for identification of metabolites or structurally similar
      compounds not previously known to be present in water samples. Two examples are
      examined in this paper from various water quality studies. They are alachlor and
      its metabolite, alachlor ethane sulfonic acid, and atrazine and its class
      members, prometryn and propazine. A method for using cross reactivity for the
      detection of these compounds is explained in this paper.

PMID- 11234803
TI  - Determination of thiabendazole in fruit juices by a new monoclonal enzyme
      immunoassay.
AB  - A competitive, indirect enzyme-linked immunosorbent assay (ELISA) for
      thiabendazole has been developed and applied to the analysis of fruit juices
      spiked with this fungicide. The immunoassay is based on a new monoclonal antibody
      derived from a hapten functionalized at the nitrogen atom in the 1-position of
      the thiabendazole structure. To our knowledge, such a structure has not been
      previously used to obtain antibodies to thiabendazole. The I50 value and the
      detection limit of the ELISA for standards were 0.2 and 0.05 ng/mL, respectively.
      Fruit juices were analyzed by diluting samples in assay buffer, without
      extraction or cleanup. Samples were not even centrifuged or filtered to remove
      fruit pulp. Under these conditions, the immunoassay was able to accurately
      determine thiabendazole down to 1 ng/mL in orange and grapefruit juices, down to
      5 ng/mL in banana juice, and down to 20 ng/mL in apple and pear juices.
      Sensitivity differences of the ELISA were caused by the minimum dilution required
      by each juice to minimize matrix effects: 1/10 for orange and grapefruit juices,
      1/50 for banana juice, and 1/100 for apple and pear juices. In an attempt to
      further increase the sensitivity of the immunoassay for matrixes showing the
      strongest interferences, apple and pear juices spiked with thiabendazole at low
      levels (1-20 ng/mL) were extracted with ethyl acetate before analysis. This
      simple procedure entailed a significant reduction of matrix effects, which in
      fact allowed us to determine accurately as low as 5 ng/mL thiabendazole in apple
      and pear juices. Irrespective of whether samples were analyzed by the direct
      dilution method or after extraction, the simplicity, sensitivity, and sample
      throughput of this monoclonal immunoassay makes it a very convenient method for
      the routine monitoring of thiabendazole residues in fruit juices.

PMID- 11234805
TI  - U.S. Food and Drug Administration--a science-based regulatory agency.

PMID- 11234807
TI  - A year of change and challenge for AOAC INTERNATIONAL.

PMID- 11234806
TI  - Assuring the integrity of olive oil products.

PMID- 11234808
TI  - Pesticide formulations: CIPAC studies. Collaborative International Pesticide
      Analytical Council.

PMID- 11234810
TI  - Drug residues in foods, diagnostics and test kits.

PMID- 11234809
TI  - Sensitive determination of n-hexane and cyclohexane in human body fluids by
      capillary gas chromatography with cryogenic oven trapping.
AB  - A sensitive method was developed for determination of n-hexane and cyclohexane in
      human body fluids by headspace capillary gas chromatography (GC) with cryogenic
      oven trapping. Whole blood and urine samples containing n-hexane and cyclohexane
      were heated in a 7.5 mL vial at 70 degrees C for 15 min, and 5 mL of the
      headspace vapor was drawn into a glass syringe. All vapor was introduced through
      an injection port of a GC instrument in the splitless mode into an Rtx-Volatiles
      middle-bore capillary column at an oven temperature of -40 degrees C for trapping
      volatile compounds. The oven temperature was programmed to 180 degrees C for GC
      with flame ionization detection. These conditions gave sharp peaks for both n
      hexane and cyclohexane, a good separation of each peak, and low background
      impurities for whole blood and urine. The extraction efficiencies of n-hexane and
      cyclohexane were 13.2-30.3% for whole blood and 12.7-20.7% for urine. The
      coefficients of within-day variation in terms of extraction efficiency of both
      compounds were 5.0-9.5% for whole blood and 3.8-10.8% for urine; those of day-to
      day variation for the compounds were not greater than 16.6%. The regression
      equations for n-hexane and cyclohexane showed good linearity in the range of 5
      500 ng/0.5 mL for whole blood and urine. The detection limits (signal-to-noise
      ratio = 3) for both compounds were 1.2 and 0.5 ng/0.5 mL for whole blood and
      urine, respectively. The data on n-hexane or cyclohexane in rat blood after
      inhalation of each compound are also presented.

PMID- 11234811
TI  - Drug residues in animal tissues.

PMID- 11234812
TI  - Phycotoxins.

PMID- 11234813
TI  - Mycotoxins.

PMID- 11234815
TI  - Sugar and sugar products.

PMID- 11234814
TI  - Food Allergens.

PMID- 11234816
TI  - Botanicals and other supplements.

PMID- 11234817
TI  - Infant formula and medical diets.

PMID- 11234818
TI  - Fats and oils.

PMID- 11234819
TI  - Dietary fiber.

PMID- 11234820
TI  - Water-soluble vitamins.

PMID- 11234822
TI  - Chocolate and cacao products.

PMID- 11234821
TI  - Fruit and fruit products.

PMID- 11234823
TI  - Cereals and cereal products.

PMID- 11234824
TI  - Seafoods.

PMID- 11234825
TI  - Radioactivity.

PMID- 11234826
TI  - Metals and other elements.

PMID- 11234827
TI  - Multiclass multiresidue methods for organic compounds.

PMID- 11234828
TI  - Simultaneous determination of E- and Z-guggulsterones in dietary supplements
      containing Commiphora mukul extract (guggulipid) by liquid chromatography.
AB  - Guggulipid, the standardized product from the extraction of the ole-gum-resin
      from the Commiphora mukul plant, has been marketed as a hypolipidemic agent. The
      ketosteroids, cis- and trans-4,17(20)-pregnadiene-3,16-dione, known as E- and Z
      guggulsterones, respectively, are the main ingredients in guggulipid. A liquid
      chromatographic method was developed for simultaneous determination of E- and Z
      guggulsterones in guggulipid preparations using synthetic E- and Z-guggulsterone
      standards. Realtively low amounts of guggulsterones (E and Z) were found in
      commercial guggulipid preparations in comparison with the manufacturer's claim of
      2.5%. The mixture of E- and Z-guggulsterones was extracted and separated on a
      Symmetry C18 reversed-phase column, with a mobile phase of acetonitrile--water
      (46 + 54, v/v) and detected at 242 nm. The retention times of E- and Z
      guggulsterones are approximately 8 and 11 min, respectively. Assay quantitation
      was based on the calibration curve obtained from a mixture of synthetic standard
      E- and Z-guggulsterones. Experimental data on selectivity, linearity, accuracy,
      and recoveries are presented.

PMID- 11234829
TI  - Single class multiresidue methods for organic compounds.

PMID- 11234830
TI  - Food microbiology--non dairy.

PMID- 11234831
TI  - Drugs in feeds.

PMID- 11234833
TI  - Antibiotics in feeds.

PMID- 11234832
TI  - Nutrients in soils.

PMID- 11234834
TI  - Feeds.

PMID- 11234843
TI  - Charm Safe-Level beta-Lactam Test for amoxicillin, ampicillin, ceftiofur,
      cephapirin, and penicillin G in raw commingled milk.
AB  - The Charm Safe-Level beta-Lactam Test was evaluated by a U.S. Food and Drug
      Administration (FDA) test protocol administered by the AOAC-Research Institute.
      The sensitivity and selectivity of the test were evaluated with >800 negative raw
      commingled and drug-fortified milk samples by the manufacturer and an independent
      laboratory. Probit analysis by the independent laboratory determined the
      following 90% positive levels with 95% confidence: amoxicillin, 5.6 ppb;
      ampicillin, 8.5 ppb; cephapirin, 13.7 ppb; ceftiofur, 46.2 ppb; and penicillin G,
      3.6 ppb. These values were within a range of +/- 20% of the manufacturer's data.
      Selection of negative samples met confidence specifications. Ruggedness
      parameters were studied and defined, and the stability of frozen milk was
      verified. There were no interferences from somatic cells (1,000,000 somatic cell
      count/mL) or bacteria (300,000 colony-forming units/mL), or from 27 other non
      beta-lactam animal drugs. Test performance with raw milk samples containing
      incurred penicillin, ampicillin, and amoxicillin was consistent with the dose
      responses determined with fortified milk samples. Incurred cephalosporin in raw
      milk samples was detected at lower levels than was cephalosporin in fortified
      milk samples, presumably because of the presence of metabolite, as verified by
      other test methods. Quality control data support consistency in manufacture
      between batches and the stability of refrigerated test reagents for up to 1 year.
      Successful fulfillment of these criteria led to FDA certification of the test
      when used with a reader in U.S. milk testing programs.

PMID- 11234849
TI  - Simultaneous determination of ascorbic acid and acetylsalicylic acid in
      pharmaceutical formulations.
AB  - A direct, simple, and practical first-derivative spectrophotometric method is
      described for simultaneous determination of ascorbic acid and acetylsalicylic
      acid. The effects of the solvent, excipients, and spectral variables on the
      analytical signal were investigated. The drugs were determined simultaneously
      with a 0.01 M methanolic hydrochloric acid solution as the solvent, and the
      signals were evaluated directly by using the zero-crossing method at 245.0 and
      256.0 nm for acetylsalicylic acid and ascorbic acid, respectively. The method
      allows the simultaneous determinations of acetylsalicylic acid and ascorbic acid
      in the ranges of 6.6 x 10(-6) to 1.5 x 10(-4)M and 3.4 x 10(-6) to 2.0 x 10(-4)M,
      respectively, with standard deviation of <2.0%. The proposed method was applied
      to determinations of these drugs in tablets.

PMID- 11234850
TI  - Determination of halofuginone and amprolium in chicken muscle and egg by liquid
      chromatography.
AB  - A liquid chromatographic (LC) method was developed for simultaneous measurement
      of halofuginone (HFN) and amprolium (APL) in chicken muscle and egg. HFN and APL
      were extracted from chicken muscle and egg with acetonitrile. In chicken egg,
      they were partially purified by solid-phase extraction (SPE) to separate them
      from impurities. The LC separation was performed on a 4.6 mm id x 250 mm TSK-gel
      ODS-80TM column using acetonitrile-McIlvaine buffer, pH 3.4, containing 0.01M
      sodium lauryl sulfate (42 + 58) as the mobile phase. Ultraviolet detection of HFN
      and APL was performed at wavelengths of 242 and 265 nm, respectively. Recoveries
      of HFN and APL from chicken muscle spiked at 0.5 microg/g were 74.8 +/- 17.7 and
      94.2 +/- 5.0%, respectively (mean +/- standard deviation [SD], n = 10). In
      chicken muscle, the lower limit of determination for both APL and HFN was 0.03
      microg/g. Recoveries of HFN and APL from chicken egg spiked at 0.5 microg/g by a
      cleanup procedure using SPE were 54.6 +/- 3.4 and 85.0 +/- 2.4%, respectively
      (mean +/- SD, n = 5). In chicken egg, the lower limit of determination for both
      APL and HFN was 0.04 microg/g.

PMID- 11234851
TI  - Preconcentration of bismuth(III) and copper(II) by solid-phase extraction and
      subsequent determination by differential pulse polarography.
AB  - A differential pulse polarographic method is proposed for the trace determination
      of bismuth and copper from large volumes of aqueous samples after adsorption of
      their 1-(2-thiazolylazo)-2-naphthol complexes onto microcrystalline naphthalene
      in the pH ranges of 7.2-9.0 and 4.0-7.8, respectively. Bismuth and copper are
      desorbed from microcrystalline naphthalene with 9 mL 1M HCl. Well-defined peaks
      are obtained at Ep = -0.09 and -0.20 V versus a saturated calomel electrode, in
      an HCl-isoquinoline medium as the supporting electrolyte, for bismuth and copper,
      respectively. Bismuth is reduced reversibly with a 3-electron change, whereas
      copper is reduced irreversibly under these conditions. The detection limits are
      55 ng/mL for bismuth and 91 ng/mL for copper. Linearity is maintained in the
      concentration ranges of 0.18-13.5 and 0.30-17.3 microg/mL for bismuth and copper,
      respectively, with corresponding correlation coefficients of 0.9996 and 0.9885.
      The relative standard deviations are 1.0% for bismuth at 2.0 microg/mL and 1.4%
      for copper at 5.0 microg/mL. Various parameters were optimized to develop
      conditions for the determination of these metal ions in various samples.

PMID- 11234852
TI  - Sensitive spectrophotometric determination of nitrite in human saliva and rain
      water and of nitrogen dioxide in the atmosphere.
AB  - A new simple, sensitive, and selective spectrophotometric method was developed
      for the determination of nitrite. The method is based on the reaction of nitrite
      with sulfathiazole in acidic medium to form a diazonium cation, which is
      subsequently coupled with N-(1-naphthyl)ethylenediamine dihydrochloride to form a
      highly stable, violet azo dye. The reaction product has an absorption maximum at
      546 nm and obeys Beer's law over a nitrite range of 0.054-0.816 microg/mL. The
      molar absorptivity of the colored compound is 4.61 x 10(4) L/mol x cm). The
      detection limit is 12.1 microg/L. The relative standard deviation is 0.85% for 5
      determinations of nitrite at 0.27 microg/mL. The reproducibility and validity of
      the proposed method are discussed in the present paper. The simplicity of the
      method is demonstrated by the high stability of the azo-dye product as well as
      the short time required for its complete formation in a reaction at room
      temperature without pH control or extra extraction. The sensitivity of the method
      is shown by the successful determination of nitrite in human saliva and rain
      water, and of nitrogen dioxide in the atmosphere. The results compare favorably
      with those obtained by the reference method. The selectivity of the method is
      indicated by its freedom from most interferences, even at high concentrations of
      nitrate (500 microg/mL).

PMID- 11234853
TI  - Determination of sulfate in natural and residual waters by turbidimetric flow
      injection analysis.
AB  - A turbidimetric flow-injection system was developed for the determination of
      sulfate in natural and residual water samples, with no previous treatment, using
      spectrophotometric detection. The precipitating agent, 7.0% (w/v) barium chloride
      solution prepared in 0.10% (w/v) polyvinyl alcohol, was added by using the
      merging-zones approach. A 100 mg/L sulfate solution in 0.07M nitric acid was
      mixed with the sample before it entered the injection loop to improve the
      detection limit, provide in-line pH adjustment, and prevent the interference of
      some anionic species. The relative standard deviations of the results were
      between 1.4 and 3.0% and were in agreement with results obtained by the reference
      method. Samples within a linear concentration range of 10-120 mg SO4(2-)/L can be
      analyzed at a rate of 40/h. The detection limit is 5 mg SO4(2-)/L.

PMID- 11234854
TI  - Rappaport-Vassiliadis medium for recovery of Salmonella spp. from low microbial
      load foods: collaborative study.
AB  - Twenty-three laboratories participated in a collaborative study to compare the
      relative effectiveness of Rappaport-Vassiliadis (RV) medium incubated at 42
      degrees C, selenite cystine (SC) broth (35 degrees C), and tetrathionate (TT)
      broth (35 and 43 degrees C) for recovery of Salmonella from the following foods
      with a low microbial load: dried egg yolk, dry active yeast, ground black pepper,
      guar gum, and instant nonfat dry milk. For dry active yeast, lauryl tryptose (LT)
      broth, incubated at 35 degrees C, was used instead of SC broth. All of the foods
      were artificially inoculated with single Salmonella serovars, that had been
      lyophilized before inoculation, at high and low target levels of 0.4 and 0.04
      colony forming units/g food, respectively. For analysis of 870 test portions,
      representing all of the foods except yeast, 249 Salmonella-positive test portions
      were detected by RV medium, 265 by TT broth (43 degrees C), 268 by TT broth (35
      degrees C), and 269 by SC broth (35 degrees C). For analysis of 225 test portions
      of yeast, 79 Salmonella-positive test portions were detected by RV medium, 79 by
      TT broth (43 degrees C), 84 by TT broth (35 degrees C), and 68 by LT broth (35
      degrees C). RV medium was comparable to, or even more effective than, the other
      selective enrichments for recovery of Salmonella from all of the foods except
      guar gum. It is recommended that RV (42 degrees C) and TT (35 degrees C) be used
      with foods that have a low microbial load, except for guar gum for which SC (35
      degrees C) and TT (35 degrees C) are recommended.

PMID- 11234855
TI  - Comparison of amplified ELISA and mouse bioassay procedures for determination of
      botulinal toxins A, B, E, and F.
AB  - The amplified enzyme-linked immunosorbent assay (amp-ELISA) was compared to the
      mouse bioassay for determination of botulinal neurotoxin types A, B, E, and F.
      Twelve different toxin-producing type A, 13 proteolytic type B, 9 nonproteolytic
      type B, 16 type E, 8 proteolytic type F, 5 nonproteolytic type F, and 6
      nontoxigenic clostridial strains were tested. The cultures were inoculated into
      cooked meat medium (CMM) and tryptone-peptone-glucose-yeast extract (TPGY)
      medium, incubated for 5 days, and then examined for biological toxicity in mice
      and amp-ELISA endpoints. The amp-ELISA was less sensitive in detecting toxins
      produced by nonproteolytic than proteolytic strains of type B and F organisms.
      All of the toxin-producing strains tested were positive by the AOAC method and
      the amp-ELISA in either undiluted TPGY or CMM culture fluids regardless of mouse
      toxicity level, source, or strain. Cross-reactivity was observed between some but
      not all of the botulinal strains tested. None of the nontoxigenic strains were
      positive by the amp-ELISA. Purified botulinal toxins were also assayed using
      these 2 methods. The sensitivity of the amp-ELISA using purified neurotoxins was
      about 0.1 ng/mL for types A, B, and E and about 1.0 ng/mL for type F.

PMID- 11234856
TI  - Determination of locust bean gum and guar gum by polymerase chain reaction and
      restriction fragment length polymorphism analysis.
AB  - A polymerase chain reaction (PCR) was developed to differentiate the thickening
      agents locust bean gum (LBG) and the cheaper guar gum in finished food products.
      Universal primers for amplification of the intergenic spacer region between trnL
      3' (UAA) exon and trnF (GAA) gene in the chloroplast (cp) genome and subsequent
      restriction analysis were applied to differentiate guar gum and LBG. The presence
      of <5% (w/w) guar gum powder added to LBG powder was detectable. Based on data
      obtained from sequencing this intergenic spacer region, a second PCR method for
      the specific detection of guar gum DNA was also developed. This assay detected
      guar gum powder in LBG in amounts as low as 1% (w/w). Both methods successfully
      detected guar gum and/or LBG in ice cream stabilizers and in foodstuffs, such as
      dairy products, ice cream, dry seasoning mixes, a finished roasting sauce, and a
      fruit jelly product, but not in products with highly degraded DNA, such as tomato
      ketchup and sterilized chocolate cream. Both methods detected guar gum and LBG in
      ice cream and fresh cheese at levels <0.1%.

PMID- 11234857
TI  - Liquid chromatographic method with electrochemical detection for determination of
      cisapride in serum.
AB  - A sensitive liquid chromatographic (LC) method using electrochemical detection
      was developed for the identification and quantitation of cisapride in serum. The
      serum samples were deproteinized by a simple acetonitrile precipitation technique
      followed by n-hexane extraction. Cisapride in the deproteinized serum was
      separated by an isocratic elution with an ODS Hypersil LC column (150 x 4.6 mm)
      using a mobile phase consisting of 0.05M Na2HPO4-acetonitrile (60 + 40), pH 8.4.
      Cisapride eluted from the column was detected by a Coulochem II electrochemical
      detector. The precision of this assay method was determined by intra- and inter
      day analyses of cisapride-free fetal bovine serum samples that were spiked with
      25, 50, and 100 ng/mL cisapride. For the intra-day assay, recoveries were 94.3 +/
      1.4, 90.1 +/- 2.9, and 103.2 +/- 9.2%, respectively. This electrochemical
      detection LC method could be very useful in monitoring plasma levels of
      cisapride.

PMID- 11234858
TI  - Physician satisfaction revisited.
AB  - Nineteen US physicians were interviewed in 1987 to identify how they defined and
      addressed the changes facing them. Attitudes and problem-solving approaches of
      physicians who remained satisfied were compared with those deemed dissatisfied.
      In this ten-year follow-up study, the original subjects were re-contacted and
      asked to describe changes in their practices, and other questions regarding their
      professional lives. They were rated by themselves and the authors for
      satisfaction. Eighteen responded and could be rearranged into three groups by
      ratings of satisfaction. Representative responses delineate each group and
      explore various aspects differentiating responses within the grouping.
      CONCLUSION: past satisfaction with medical practice is no predictor of current
      satisfaction. Only those who either embraced change or found a means of escape
      from the issues facing them earlier were judged satisfied. The majority describe
      strategies to reduce fatigue, and to maintain some control over their
      professional lives.

PMID- 11234859
TI  - Doctor-parent-child communication. A (re)view of the literature.
AB  - Studies on doctor-patient communication focus predominantly on dyadic
      interactions between adults; even when the patient is a child, the research focus
      is usually on doctor-parent interaction. The aim of this review study is to
      evaluate the state of the art of research into doctor-parent-child communication,
      and to explore the specific role of the child. Researchers have focused on
      diverse aspects of the communication in this triad, and, as a result, knowledge
      gained from studies in this area is poorly integrated. Most of the studies have
      ignored the implications of a child's presence in medical encounters. Although
      all studies claim to examine the interaction in the doctor-parent-child triad,
      most research methodologies used are based on dyads. Our claim. however, is that,
      because the interactional dynamics of a triad differ fundamentally from those of
      a dyad, triadic analyses are a prerequisite for a full account of the
      communication between doctor, parent and child. Suggestions are formulated for an
      adequate research frame regarding triads.

PMID- 11234860
TI  - Community values and preferences in transplantation organ allocation decisions.
AB  - This paper is concerned with community values and preferences in organ
      transplantation allocation decisions. With recent trends in organ shortages,
      transplant teams face difficult allocation decisions amongst increasing numbers
      of "worthy" potential recipients. It is argued that the debate about these
      decisions ought to be informed in part by a systematic knowledge of prevailing
      community standards. A community sample of 238 adults (140 women and 98 men, with
      a mean age of 47.0 years) completed a questionnaire concerning which factors
      ought to affect recipient priority for transplantation. Longer waiting time,
      better prognosis, younger age and being a parent were the most frequently
      selected criteria for organ allocation decisions. The participants also rank
      ordered 16 potential recipients presented in the form of case scenarios in terms
      of priority for transplantation. The 16 case scenarios were constructed from a
      factorial combination of four variables: age of recipient (young vs old); the
      time the recipient had been on a waiting list (long vs short); recipient
      prognosis (excellent vs fair); and parental status (children vs no children). It
      was found that one case scenario involving a young parent with an excellent
      prognosis and long waiting time was ranked first by 75.2% of all participants.
      Analysis revealed that transplant recipient age and prognosis were the most
      influential factors in determining the priority rankings for organ allocation.
      The study has demonstrated that judgement and decision analysis procedures can be
      used to elicit community values and preferences about complex resource allocation
      decisions.

PMID- 11234861
TI  - Cost effectiveness of brief interventions for reducing alcohol consumption.
AB  - The direct costs and health effects of a primary-care-based brief intervention
      for hazardous alcohol consumption were examined. The total cost of the
      intervention was calculated from costs associated with: marketing the
      intervention programme; providing training and support in the use of the
      intervention materials; physician time required for providing brief advice for
      'at-risk' drinkers. The effect of the intervention on health outcomes was
      expressed in terms of number of life years saved by preventing alcohol-related
      deaths. This was derived by combining estimates of the impact of the programme if
      it were implemented nationally with available evidence on the health effects of
      excess alcohol consumption. Results are based on international trial evidence
      showing the physical resources required by the intervention and its effectiveness
      combined with Australian price data. The costs associated with screening and
      brief advice using the current intervention programme range from Aus$19.14 to
      Aus$21.50. The marginal costs per additional life year saved were below Aus$1873.
      The robustness of the model used is supported by an extensive sensitivity
      analysis. In comparison with existing health promotion strategies the costs and
      effects of the current intervention are highly encouraging.

PMID- 11234862
TI  - Who rules? The new politics of medical regulation.
AB  - The recent politicization of medical regulation in the United Kingdom has
      destabilized the historic relationship between medicine, society and the state.
      The purpose of this article is to present a political analysis of that
      relationship and its likely future by identifying the essential elements of power
      which determine its composition and its capacity to change. That analysis is in
      three parts. First, it identifies the underlying political tensions in the
      relationship between medicine, society and the state and the implications of
      those tensions for any proposed settlement on the future of medical regulation.
      What are the political criteria by which such a settlement must be judged if the
      tensions are to be resolved? Secondly, it explores the ideological conflict
      concerning the nature of medical regulation between the major players, the
      expression of that conflict in their use of quite different discourses, and the
      incompatibility of the power assumptions contained therein. Thirdly, it examines
      the medical profession's particular response to the pressures for change.
      Finally, the article reflects on the necessary dialogue which must take place
      between medicine, society and the state before a lasting resolution of the
      present tensions can be achieved.

PMID- 11234863
TI  - Private practitioners and their role in the resurgence of malaria in Mumbai
      (Bombay) and Navi Mumbai (New Bombay), India: serving the affected or aiding an
      epidemic?
AB  - The increased emphasis on privatization of the health care sector in many
      developing countries by international financial institutions and national
      governments expects an expanding role for private health care practitioners in
      the management of major communicable diseases such as tuberculosis, malaria,
      acute respiratory infections (ARIs) and sexually transmitted diseases (STDs).
      Largely unexamined in the Indian context, however, is the socio-cultural context,
      the micro-level political environment in which private practitioners carry out
      their activities, and the quality of care they provide to their patients.
      Examining these aspects is significant given the impressive growth of the
      country's private health sector during the past decade. This paper reports the
      results of an ethnographic study carried out in Mumbai (Bombay) and Nav Mumbai
      (New Bombay), India on private general practitioners (GPs) and their role in the
      management of malaria at a time when these two neighboring cities were in the
      midst of the worst malaria epidemic in over 60 years. Described are the
      characteristics of a sample of 48 private practitioners from the two cities, and
      their clinics. This is followed by a discussion of the data gathered through
      untructured interviews with practitioners and patients, and complemented by
      observational data on doctor-patient encounters gathered at 16 clinics over a 9
      month period. The findings of the study suggest that many practitioners in Mumbai
      and Navi Mumbai were poorly qualified and did not play a supportive role in the
      two cities' public health departments to bring the epidemic under control. The
      majority of the practitioners adopted diagnostic and treatment practices that
      were not consistent with the guidelines laid down by WHO and India's National
      Malaria Eradication Programme. Very few practitioners, especially those
      practicing in low-income areas, relied on a peripheral blood-smear test to make a
      diagnosis. Practitioners whose clientele was mostly the poor commonly resorted to
      giving one-day treatment to febrile patients that included injectable
      antimalarials and broad spectrum antibiotics. Such practitioners justified their
      mode of diagnosis and treatment by asserting that they were only responding to
      the demands placed on them by their patients who could not afford a blood-smear
      test or a full prescription. The paper argues that practitioners who acquiesced
      to patient demands were at once exacerbating the health problems of their
      patients and jeopardizing the prospects for the epidemic to be brought under
      control. Driven primarily by the need to retain the patronage of patients and
      maintain one's popularity in a highly competitive health arena, many providers
      practiced medicine that was unethical and dangerous. The paper concludes by
      discussing the ramifications of this study for malaria control in Mumbai and Navi
      Mumbai, and highlights a few salient health policy issues concerning the growth
      of the private health sector in India and its regulation.

PMID- 11234864
TI  - Adult outpatients with depression: worse quality of life than in other chronic
      medical diseases in Argentina.
AB  - Current research into the impact of major depressive illness on society goes
      beyond estimating its prevalence, complications or comorbidity patterns, to
      include research that seeks to establish how this disorder affects individuals'
      daily functioning and well-being. However, it is unclear whether depression
      affects such broadly defined quality of life (QOL) outcomes to a similar or an
      even greater extent than chronic physical illness. The present study assessed QOL
      in a sample of 48 ambulatory depressed patients who sought psychiatric assistance
      at a centre in La Plata, Argentina, during a 15-month period. All of them met DSM
      IV criteria for current major depression, as diagnosed by clinicians. For the
      purposes of comparison, we also evaluated the QOL of additional samples of
      persons who were healthy or who had chronic physical illness. QOL was assessed
      with the WHOQOL-100, a generic and transcultural instrument developed
      simultaneously in 15 centres, by the World Health Organization (WHO). Results
      indicated that QOL was significantly poorer in depressed persons than in either
      healthy persons or individuals with other frequent chronic pathologies in
      Argentina. The impact of depression was also found to be related to the
      seriousness of the episode. We suggest that it is important to include QOL
      assessments of patients with depressive disorders when evaluating the course and
      progress of their treatment. Such assessments can be used in health care decision
      making and resource allocation.

PMID- 11234865
TI  - Problems with the sickness impact profile: a theoretically based analysis and a
      proposal for a new method of implementation and scoring.
AB  - The Sickness Impact Profile (SIP) is one of the most widely used health status
      measures, but there are problems with the measure that lead to inconsistent and
      illogical scores. There are many desirable features to the SIP development
      methodology in that it is based on a good range of items and the item weightings
      are valuable. The current method of scoring the SIP is the use of a summated
      total and was selected based on limited empirical evidence. However, in this
      paper we argue that there are problems with the SIP because the current
      empirically derived method of scoring is incompatible with both the underlying
      theoretical scaling framework (Thurstone scaling) and the nature of the items in
      the SIP. In addition, the items do not have properties consistent with the
      scaling methodology. We suggest that it is crucial to take both a theoretical and
      empirical approach to selecting a scoring method. To examine problems associated
      with the SIP we explored the underlying scaling methodology and identified the
      types of items in the SIP. A new method of scoring is proposed that is consistent
      with the items and scaling in the SIP, namely using the maximum individual
      weighting from the items that were checked as a category score. This new method
      of scoring resolves many of the previously observed problems in the SIP. The new
      method of scoring also presented the opportunity for a new implementation of the
      SIP that reduces the number of items that most respondents, especially those with
      severe limitations, would be asked. Without taking a theoretical approach to
      scoring we suggest that subsequent, empirically based, scale amendments are
      unlikely to solve the problems. It is proposed that this new method of scoring
      justifies a thorough empirical investigation.

PMID- 11234866
TI  - Can I afford free treatment?: Perceived consequences of health care provider
      choices among people with tuberculosis in Ho Chi Minh City, Vietnam.
AB  - Vietnam has a well-organised National TB Control Programme (NTP) with outstanding
      treatment results. Excellent prospect of cure is provided free of charge. Still,
      some people prefer to pay for their TB treatment themselves in private clinics.
      This is a potential threat to TB control since no notification of cases treated
      in the private sector occurs, and there is no control of the effectiveness of
      treatment provided in private clinics. Using a qualitative approach within a
      grounded theory framework, this study explores health-seeking behaviour among
      people with TB, applying a specific focus on reasons for choices of private
      versus pubic health care providers. The study identifies a number of
      characteristics of private TB care, which both seem attractive to patients and at
      the same time contrast sharply with the structure of the NTP strategy. These
      include flexible diagnostic procedures, no administrative procedures to establish
      eligibility for treatment, flexible choices of drug regimens, non-supervised
      treatment (no DOT), no tracing of defaulters in the household, no official
      registration of TB cases and thus less threat to personal integrity. A
      possibility to demand individualised service through the use of fee-for-service
      payments directly to physicians also seems attractive to many patients. A number
      of the components of the NTP strategy that have been put in place in order to
      secure optimal public health outcomes are lacking in the private sector. A
      dilemma for TB control is that this seems to be an important reason for why many
      people with TB opt for private providers where quality of care is virtually
      uncontrolled. The global threat of TB has led to calls for forceful measures to
      control TB. However, based on the findings in this study it is argued that the
      use of rigid approaches to TB control that do not encompass a strong component of
      responsiveness towards the needs of individuals may be counterproductive for
      public health.

PMID- 11234867
TI  - The will to live: gender differences among elderly persons.
AB  - The purpose of the study was to investigate the will to live by evaluating its
      association with the wish to prolong life and with indicators of well-being among
      men and women. First were assessed the strength of the will to live, and its
      relationship to the wish to prolong life in hypothetical illness conditions.
      Next, association between the will to live and explanatory factors, such as
      religious beliefs, fear of death and dying, physical and psycho-social dimensions
      of well-being were comparatively evaluated among men and women. Data were
      collected from a random sample of 987 Israeli elderly persons by structured
      interviews at the participants' homes. Findings indicated that women express a
      significantly weaker will to live than men, and less desire to prolong life by
      medical interventions in all the hypothetical health conditions presented to
      them. Gender differences were also found on the variables which contribute to the
      explanation of the will to live: For both genders, psycho-social indicators of
      well-being had more explanatory power than health indicators of well-being, but
      this finding was more striking among women. The implications of these findings
      for the study of the perceived meaningfulness of life, and the potential use of
      the will to live as an indicator of well-being are discussed.

PMID- 11234868
TI  - Domestic labour, paid employment and women's health: analysis of life course
      data.
AB  - The relationship between the amount of domestic labour performed by a woman
      during her lifetime and a variety of self-reported and objective measures of her
      health in early old age was examined in the female members (n = 155) of a data
      set containing considerable life course information, including full household,
      residential and occupational histories. Domestic labour, on its own, proved a
      weak predictor of health. The relationship strengthened when domestic labour was
      combined with the hazards of the formal paid employment which the woman had
      performed. This suggests that it is the combination of domestic labour plus paid
      employment which influences women's health. The robustness of this conclusion is
      indicated by its agreement with other studies which reached the same conclusion
      through an analysis of data with markedly different characteristics.

PMID- 11234869
TI  - Networks, resources and risk among women who use drugs.
AB  - The public health tradition of intervening at the environmental level has not
      been fully exploited in terms of HIV prevention efforts among drug users. Women
      who use drugs are at particularly high risk of acquiring HIV and other blood
      borne and sexually transmitted infections, such as hepatitis B (HBV) and
      hepatitis C (HCV), and could potentially benefit from environmental level
      interventions. In a review of the existing literature, we examine the extent to
      which the linkages among multiple causal levels may contribute to the disease
      transmission risk experienced by women who use drugs. The multiple causal levels
      of risk potentially involved in the transmission dynamics of infectious pathogens
      include biological, behavioral, dyadic relationship, network, and structural
      levels. Biological and behavioral risk factors have already been examined in
      depth; yet, little empirical research currently exists for other causal levels.
      Increasingly, investigators suggest that the character and dynamics of
      relationships with sex partners may be an important determinant of risk, both for
      engaging in risk behaviors and for doing so with high-risk partners. The
      influence of higher-order causal level factors, specifically network and
      structural factors, are the least well documented, but are posited to be a
      principal underlying cause of the current differential HIV incidence rates
      between men and women who use drugs. Future research should focus on these higher
      order causal levels, in order to better understand disease transmission dynamics;
      to better evaluate the limitations, as well as the opportunities, of current
      intervention efforts; to develop interventions that improve and supplement
      current HIV prevention efforts among women who use drugs; and to inform public
      policy debate.

PMID- 11234870
TI  - Statistical analysis.

PMID- 11234871
TI  - Stealth liposomes and tumor targeting: one step further in the quest for the
      magic bullet.

PMID- 11234872
TI  - The clinical implications of gemcitabine radiosensitization.

PMID- 11234873
TI  - Why drugs fail: of mice and men revisited.

PMID- 11234874
TI  - Phase I and pharmacokinetic study of ecteinascidin 743 administered as a 72-hour
      continuous intravenous infusion in patients with solid malignancies.
AB  - Ecteinascidin 743 (ET-743) is a cytotoxic tetrahydroisoquinoline alkaloid that
      covalently binds to DNA in the minor groove. The in vitro chemosensitivity of
      cancer cells to ET-743 is markedly enhanced by prolonging the duration of
      exposure to the drug. A Phase I study of ET-743 given as a 72-h continuous i.v.
      infusion every 21 days was performed. Characteristics of the 21 adult patients
      with refractory solid tumors enrolled in the study were as follows: (a) 12 men;
      (b) 9 women; (c) median age, 59 years; (d) Eastern Cooperative Oncology Group
      performance status < or = 1, 20 patients; and (e) two prior regimens of
      chemotherapy, 7 patients. Dose limiting toxicity (DLT) was defined by typical
      criteria, except that grade 3 transaminitis did not constitute a DLT. There were
      no DLTs in the six patients evaluated at the first two dose levels of 600 and 900
      microg/m2. Reversible grade 4 transaminitis occurred in two of nine patients
      after treatment with the first cycle of therapy at the third dose level of 1200
      microg/m2. Another patient experienced grade 4 rhabdomyolysis, renal failure
      requiring hemodialysis, grade 4 neutropenia, and grade 3 thrombocytopenia during
      the second cycle of therapy with this dose. The maximum tolerated dose was 1200
      microg/m2, and an additional six patients were enrolled at an intermediate dose
      level of 1050 microg/m2. This well-tolerated dose was established as the
      recommended Phase II dose. The disposition of ET-743 was distinctly
      biexponential, and a departure from linear pharmacokinetic behavior was evident
      at the 1200-microg/m2 dose level. Pharmacokinetic parameters determined at 1050
      microg/m2 were (mean +/- SD): maximum plasma concentration, 318 +/- 147 pg/ml;
      initial disposition phase half-life, 9.0 +/- 10.3 min; terminal phase half-life,
      69.0 +/- 56.7 h; and total plasma clearance, 28.4 +/- 22.5 liters/h/m2. Prolonged
      systemic exposure to concentrations of the agent that are cytotoxic in vitro were
      achieved. Toxicity of the drug is clearly schedule-dependent, because increasing
      the duration of infusion from 3 or 24 h to 72 h results in decreased
      myelosuppression and comparable hepatotoxicity. Although there were no objective
      responses to therapy, clear evidence of antitumor activity was observed in a
      patient with epithelioid mesothelioma, as confirmed by positron emission
      tomography studies. A Phase II trial to assess the efficacy of ET-743 against
      this highly refractory neoplasm has been initiated on the basis of this
      observation. The therapeutically optimal administration schedule remains to be
      established, inasmuch as there have been indications of activity against a
      variety of tumors during Phase I studies when the drug was infused over times
      ranging from 1 to 72 h. Characterizing the pharmacokinetics of ET-743 during the
      course of Phase II trials and Phase I combination studies is recommended to
      assure that this promising new anticancer drug can be used with an acceptable
      margin of safety.

PMID- 11234875
TI  - Effective targeting of solid tumors in patients with locally advanced cancers by
      radiolabeled pegylated liposomes.
AB  - The biodistribution and pharmacokinetics of (111)In-DTPA-labeled pegylated
      liposomes (IDLPL) were studied in 17 patients with locally advanced cancers. The
      patients received 65-107 MBq of IDLPL, and nuclear medicine whole body gamma
      camera imaging was used to study liposome biodistribution. The t(1/2beta) of
      IDLPL was 76.1 h. Positive tumor images were obtained in 15 of 17 studies (4 of 5
      breast, 5 of 5 head and neck, 3 of 4 bronchus, 2 of 2 glioma, and 1 of 1 cervix
      cancer). The levels of tumor liposome uptake estimated from regions of interest
      on gamma camera images were approximately 0.5-3.5% of the injected dose at 72 h.
      The greatest levels of uptake were seen in the patients with head and neck
      cancers [33.0 +/- 15.8% ID/kg (percentage of injected dose/kg)]. The uptake in
      the lung tumors was at an intermediate level (18.3 +/- 5.7% ID/kg), and the
      breast cancers showed relatively low levels of uptake (5.3 +/- 2.6% ID/kg). These
      liposome uptake values mirrored the estimated tumor volumes of the various tumor
      types (36.2 +/- 18.0 cm3 for squamous cell cancer of the head and neck, 114.5 +/-
      42.0 cm3 for lung tumors, and 234.7 +/- 101.4 cm3 for breast tumors). In
      addition, significant localization of the liposomes was seen in the tissues of
      the reticuloendothelial system (liver, spleen, and bone marrow). One patient with
      extensive mucocutaneous AIDS-related Kaposi sarcoma was also studied according to
      a modified protocol, and prominent deposition of the radiolabeled liposomes was
      demonstrated in these lesions. An additional two patients with resectable head
      and neck cancer received 26 MBq of IDLPL 48 h before undergoing surgical excision
      of their tumors. Samples of the tumor, adjacent normal mucosa, muscle, fat, skin,
      and salivary tissue were obtained at operation. The levels of tumor uptake were
      8.8 and 15.9% ID/kg, respectively, with tumor uptake exceeding that in normal
      mucosa by a mean ratio of 2.3:1, in skin by 3.6:1, in salivary gland by 5.6:1, in
      muscle by 8.3:1, and in fat by 10.8:1. These data strongly support the
      development of pegylated liposomal agents for the treatment of solid tumors,
      particularly those of the head and neck.

PMID- 11234876
TI  - The toxicity of deglycosylated ricin A chain-containing immunotoxins in patients
      with non-Hodgkin's lymphoma is exacerbated by prior radiotherapy: a retrospective
      analysis of patients in five clinical trials.
AB  - A retrospective analysis of 102 patients with relapsed, non-Hodgkin's lymphoma
      treated with two different ricin A chain-containing immunotoxins (ITs) in five
      Phase I clinical trials indicates that the dose-limiting toxicity, vascular leak
      syndrome, was more frequent and more severe in patients who had undergone prior
      radiotherapy (RT). Excluding patients with prior RT from the calculations of the
      maximum tolerated dose indicates that the maximum tolerated doses of these ITs
      had not been reached in any trial and are clearly higher than reported
      previously. Excluding patients with prior RT from future clinical trials may
      increase the dose of ITs that can be given in the absence of severe vascular leak
      syndrome.

PMID- 11234877
TI  - Multiple high-grade bronchial dysplasia and squamous cell carcinoma: concordant
      and discordant mutations.
AB  - Loss of heterozygosity (LOH) involving chromosomes 3p, 5q, 9p, or 17p and
      aberrant expression or mutation of p53 are reported previously in selected
      bronchial dysplasias and squamous cell cancers (SCCs). Yet, comprehensive
      analyses of LOH patterns at these chromosomal sites and of p53 alterations are
      not reported for histologically normal bronchial epithelium, high-grade bronchial
      dysplasia, and SCC present in the same pulmonary resections. Whether concordant
      or discordant genetic changes are detected in these bronchial tissues, especially
      when multiple high-grade dysplastic bronchial lesions are present, was studied.
      Genomic DNA was microdissected from eight pulmonary SCCs and high-grade
      dysplastic lesions that were associated with SCC. In four cases, two independent
      high-grade dysplastic bronchial lesions were identified. When available,
      histologically normal bronchial epithelium was microdissected. Germ-line genomic
      DNA was isolated from normal lymph nodes. LOH was assessed for 15 microsatellite
      markers on chromosomes 3p, 5q, 9p, or 17p, sites frequently deleted in lung
      cancers. Immunohistochemical p53 expression was studied and correlated with p53
      DNA sequence analyses. Progressive LOH for these markers was found when SCCs were
      compared with high-grade dysplasia and histologically normal bronchial epithelium
      present in the same resections. Histologically normal bronchial specimens had LOH
      in up to 27% of informative markers. High-grade dysplastic lesions exhibited LOH
      for 18-45% and SCC had LOH for 18-73% of the markers. Common regions of LOH were
      found in some dysplasias compared with SCCs. In other dysplasias, discordance was
      found relative to SCCs, especially for p53 mutations. In cases with a single or
      second high-grade dysplasia associated with SCC, heterogeneity in LOH markers was
      detected. These concordant and discordant changes were consistent with convergent
      and divergent clonal selection pathways in pulmonary squamous cell
      carcinogenesis. Some histologically normal bronchial epithelial tissues had
      genetic changes more similar to those in the SCCs than in dysplastic lesions. DNA
      loss or mutations accumulate in SCC, but discordant genetic changes can exist in
      the same carcinogen-exposed bronchial tissues. These findings have implications
      for lung cancer prevention trials.

PMID- 11234878
TI  - Regulation of the urokinase-type plasminogen activator receptor gene in different
      grades of human glioma cell lines.
AB  - We reported previously that the production of urokinase-type plasminogen
      activator receptor (uPAR) protein is greater in high-grade glioblastomas than in
      low-grade gliomas. Transcriptional activation of the uPAR gene or increased
      stability of the uPAR mRNA that encodes this protein could cause the increased
      production of this protein in cell lines of different grades of gliomas. We found
      similar half-life of uPAR mRNA of 10-12 h in glioblastoma multiforme (UWR3) and
      anaplastic astrocytoma (SW1783) cells. However, the human uPAR promoter was up
      regulated 6-8-fold in SW1783 cells and 11-13-fold in UWR3 cells as compared with
      its activity in low-grade gliomas, a finding that correlates well with previous
      findings of increases in uPAR mRNA and protein levels in higher-grade gliomas.
      uPAR mRNA level was increased 11-fold over a 24-h period in low-grade glioma cell
      lines after treatment with phorbol myristate acetate. The region spanning -144 to
      -123 bp of the human uPAR promoter that contains the Sp-1 site and a PEA-3
      element and an AP-1 site at -184 plays major roles in uPAR promoter activity in
      glioblastoma cells. Specific antibodies used in an electrophoretic mobility shift
      assay identified fra-1, fra-2, Jun D, and c-Jun proteins in the nuclear protein
      complex that bind a 51-mer containing the AP-1 consensus sequence at -184 and its
      flanking sequences in the uPAR promoter. We further studied the inhibition of
      uPAR promoter by coexpression of a transactivation domain lacking C-Jun; a
      dominant-negative ERK1 and ERK2 mutant and a dominant-negative C-raf in
      glioblastoma cell lines showed the repressed uPAR promoter activity compared with
      the effect of the empty expression vector. We conclude from our findings that
      increased transcription is the more likely mechanism underlying the increase in
      uPAR production in high-grade gliomas.

PMID- 11234879
TI  - Preserved Smad4 expression in the transforming growth factor beta signaling
      pathway is a favorable prognostic factor in patients with advanced gastric
      cancer.
AB  - The signals of the transforming growth factor beta (TGF-beta) superfamily are
      conveyed through cell surface serine/threonine kinase receptors to the
      intracellular mediators known as Smads. Activation of Smads causes their
      translocation from the cytoplasm to the nucleus, where they function to control
      gene expression. The present study analyzed the expression of Smad4 and TGF-beta1
      to determine their prognostic significance in advanced gastric cancer. Of 249
      cases of advanced gastric cancer, 41 had invaded the muscular layer, 114 had
      invaded the subserosal layer, and 94 had invaded the serosa. Anti-Smad4 and TGF
      beta1 antibodies were used for immunohistochemical staining. Reduced expression
      of Smad4 was 75.1%, whereas positive expression of TGF-beta1 was 39.6% in gastric
      cancer. Smad4 expression was related to the depth of tumor invasion (P < 0.05),
      and TGF-beta1 expression correlated with tumor gross type (P < 0.05).
      Postoperative survival analysis indicated that patients who had a tumor with
      reduced Smad4 expression had a poorer clinical outcome than those with preserved
      expression (P < 0.05). Furthermore, in patients with TGF-beta1-positive tumors,
      survival rate was significantly better in patients with preserved Smad4
      expression than in those with reduced Smad4 expression (P < 0.05). According to
      multivariate analysis, Smad4 expression acted as an independent prognostic
      factor. Smad4 expression, particularly in the TGF-beta pathway, is an effective
      predictor of outcome for patients with advanced gastric cancer.

PMID- 11234880
TI  - Search for mouse mammary tumor virus-like env sequences in cancer and normal
      breast from the same individuals.
AB  - We have reported previously that a 660-bp sequence homologous to the env gene of
      the mouse mammary tumor virus, but not to the known endogenous retroviruses, was
      present in 38% of human breast cancers (Y. Wang et al., Cancer Res., 55: 5173
      5179, 1995). A unique 250-bp internal sequence was equally present in formalin
      fixed breast carcinoma. It was not detected in normal human breasts or in other
      tumors. In this study, we have investigated whether this 250-bp env sequence was
      also present in the formalin-fixed normal tissues of individuals with env
      sequence-positive breast cancer. Separate paraffin-embedded sections from breast
      carcinoma and normal breast tissues from the same individual were obtained from
      the Cooperative Breast Cancer Tissue Registry of the National Cancer Institute.
      The 250-bp env sequence was detected in 30.1% of the 106 tumors but in only 1 of
      the 106 normal breast tissues. These results indicate that the sequence is absent
      in normal tissues and thus is not genetically transmitted. This strongly implies
      that it is of exogenous origin.

PMID- 11234881
TI  - Correlation of tissue and plasma RANTES levels with disease course in patients
      with breast or cervical cancer.
AB  - The beta-chemokine RANTES was measured in plasma in 43 patients with breast
      cancer and in 23 patients with cervical cancer, and the RANTES content in primary
      tumors, tumor metastatic to lymph nodes, and clinically normal skin or pelvic
      mucosa was measured. In addition, plasma levels were determined in all of the
      patients for the platelet-derived chemokine beta-thromboglobulin (beta-TG) and
      for IFN-gamma, interleukin (IL)-2, IL-4, IL-5, and IL-10, along with serum IgE
      levels and blood eosinophils. Plasma RANTES levels were found to be higher in
      order of stages IV, III, II, and I of each cancer except for stage I. A marked
      increase in plasma RANTES level (> 10,000 pg/ml) was found in 27% of patients
      with progressive malignancy but in none of those in clinical remission. The
      platelet RANTES content was correspondingly decreased in those patients with
      increased plasma RANTES levels. Beta-TG showed a pattern similar to RANTES both
      in plasma and platelets, but with much less dramatic differences between patients
      with different stages of disease. Other allergic parameters, IgE, eosinophils and
      plasma IFN-gamma, IL-2, -5, and -10, were not elevated in the cancer patients.
      The RANTES content was markedly elevated in the primary tumor and metastatic
      lesions (lymph node or skin) from all of the patients with breast or cervical
      cancer, irrespective of the plasma RANTES level. In addition, in patients with
      progressive breast or cervical cancer, but not in patients thought to be cured of
      these tumors, the RANTES content was markedly increased in clinically normal
      tissue taken from near the operative site several months postoperatively, as well
      as in intact skin or mucosa taken perioperatively near the excised tumor. This
      study suggests an as-yet-undefined but important role played by RANTES in
      carcinogenesis, as well as the possibility that a RANTES assay in tissue
      surrounding a tumor or postoperative tumor site may help predict prognosis in
      these patients.

PMID- 11234882
TI  - Overexpression of p53 in tumor-distant epithelia of head and neck cancer patients
      is associated with an increased incidence of second primary carcinoma.
AB  - Second primary carcinoma is a peculiar feature of head and neck cancer and
      represents a form of treatment failure distinct from the recurrence of the
      primary tumor. Whether altered p53 expression in tumor-distant epithelia at the
      time of diagnosis is of clinical value as a biomarker for second primary
      carcinoma development has not been rigorously answered because of the lack of
      long-term follow-up studies involving a sufficiently large patient cohort. In
      this prospective study, we have investigated p53 expression in tumor-distant
      epithelia and in the corresponding primary tumors of 105 head and neck cancer
      patients by immunohistochemistry on frozen sections. After a median follow-up of
      55 months, the clinical course of disease parameters, i.e., local recurrences,
      lymph node and distant metastasis, incidence of second primary carcinoma, and
      survival, was evaluated. Overexpression of p53 in tumor-distant epithelia was
      found in 49 patients (46.7%), and it was independent of the p53 protein status of
      the primary tumor and of the tumor site, size, stage, and grading. Mucosal p53
      overexpression was not associated with local primary recurrences, lymph node or
      distant metastases, or overall survival. Importantly, mucosal p53 overexpression,
      but not overexpression in the primary tumors, was significantly associated with
      an increased incidence of second primary carcinomas (P = 0.0001; Fisher's exact
      test). When the times to second primary tumor occurrence were analyzed by the
      Kaplan-Meier method, the difference remained significant (P = 0.005; log rank
      test). We conclude that IHC staining for p53 overexpression in tumor-distant
      epithelia provides a simple and rapid tool to identify head and neck cancer
      patients at increased risk of developing second primary tumors. Because p53
      overexpression in these epithelia in our patient cohort was specifically
      associated with second primary cancer but not with recurrences, at least a
      fraction of the second primary cancers appears to have resulted from genetic
      events in the mucosa ("field cancerization").

PMID- 11234883
TI  - Cloning and characterization of a novel gene, DRH1, down-regulated in advanced
      human hepatocellular carcinoma.
AB  - Few genes related to carcinogenesis and progression of hepatocellular carcinoma
      (HCC) have been identified to date. In the present study, we report the cloning
      and characterization of a novel gene, DRH1, which is frequently down-regulated in
      HCC. The full-length DRH1 clone contains an open reading frame of 1257
      nucleotides encoding 419 amino acids. The deduced DRH1 protein shows 41% identity
      to VDUP1, expression of which is rapidly induced by 1,25-dihydroxyvitamin D3. The
      DRH1 gene was localized to chromosome 15, and DRH1 protein was mainly observed in
      the cytoplasm of transiently transfected cells. Real-time quantitative reverse
      transcription-PCR analysis showed that the expression level of DRH1 was reduced
      in 29 of 35 (83%) HCCs compared with corresponding noncancerous liver tissue. The
      average (mean +/- SE) ratio of DRH1 expression level in tumor to corresponding
      noncancerous tissue was significantly different between well, moderately, and
      poorly differentiated HCCs (1.15 +/- 0.23, 0.69 +/- 0.10, and 0.19 +/- 0.04,
      respectively) and between HCCs without and with vascular invasion (0.94 +/- 0.16
      and 0.46 +/- 0.07, respectively). These results indicate that the down-regulation
      of DRH1 occurs not at an early stage but rather at a late stage of HCC
      progression. Although the function of DRH1 protein is still unknown, our findings
      suggest that DRH1 is related to the progression of HCC and may provide a new
      prognostic factor.

PMID- 11234884
TI  - Mutations of PTEN/MMAC1 in primary prostate cancers from Chinese patients.
AB  - PTEN/MMAC1 is a putative tumor suppressor gene located on 10q23, one of the most
      frequently deleted chromosomal regions in human prostate cancer. Although
      mutations of PTEN have often been detected in metastases of prostate cancer,
      localized tumors have shown lower rates of mutation, which have varied from 0 to
      20% among different studies. It is unknown whether the rate of PTEN mutations is
      different in prostate cancer from Asian men compared with Western men. To further
      clarify the role of PTEN in prostate cancer and to examine the gene for mutations
      in Asian men, we analyzed 32 cases of primary prostate cancers from Chinese
      patients, each of whom was not diagnosed by screening with serum prostate
      specific antigen, for PTEN mutations using the methods of tissue microdissection,
      single-strand conformational polymorphism, and direct DNA sequencing. Seventy %
      of the tumors were Gleason scores 8-10, whereas the remainder were Gleason score
      7. Six metastases of prostate cancer from American patients were also analyzed.
      Five of 32 (16%) primary prostate cancers from Chinese men and two of six
      metastases from American men showed mutations in a total of 10 codons of PTEN,
      which involved exons 1, 2, 5, 8, and 9. Two of the mutations were truncation
      type, whereas the rest were missense mutations. The mutation frequency in these
      cases from Asian patients was higher than that in our previous study of cases in
      radical prostatectomy specimens from American men, in which the 40 primary tumors
      were lower grade and had been detected by serum prostate-specific antigen test.
      We conclude that mutation of PTEN occurs more often in primary prostate cancers
      of Chinese men, whose tumors are high grade and reflective of an unscreened
      population.

PMID- 11234885
TI  - Expression of p8 in human pancreatic cancer.
AB  - The p8 gene is a recently identified gene with mitogenic activity. p8 expression
      is induced in acute pancreatitis, pancreatic development, and regeneration.
      However, the expression of p8 in pancreatic cancer is not reported. We
      investigated p8 expression in 72 human pancreatic tissues, including 38
      pancreatic cancers (PCs), by immunohistochemistry. p8 was overexpressed (positive
      cells >25% in 1,000 cells) in 71% (27 of 38) of PCs, but in only 17% (3 of 18) of
      chronic pancreatitis cases. There was no overexpression in mucinous cystadenoma
      or in normal pancreas. The p8 overexpression rate in PC was significantly higher
      than that in other conditions (P < 0.05). Reverse transcription-PCR analysis
      confirmed p8 mRNA overexpression (tumor/nontumor ratio >2) in 75% (3 of 4) of
      PCs. p8 was overexpressed also in human pancreatic cancer cell lines (MIA PaCa-2
      and PANC-1). These results suggest that p8 is involved in the development of
      pancreatic cancer, reflecting its mitogenic activity.

PMID- 11234886
TI  - The role of apoptosis in 2',2'-difluoro-2'-deoxycytidine (gemcitabine)-mediated
      radiosensitization.
AB  - The nucleoside analogue Gemcitabine [2',2'-difluoro-2'-deoxycytidine (dFdCyd)] is
      active against a wide variety of solid tumors and is a potent radiation
      sensitizer. Because apoptosis has been shown to be an important mechanism of cell
      death for many cancers, we wished to investigate the role of apoptosis in dFdCyd
      mediated radiosensitization. We evaluated HT29 colon cancer cells, UMSCC-6 head
      and neck cancer cells, and A549 lung cancer cells, which differ substantially in
      the ability to undergo radiation-induced apoptosis. We hypothesized that if
      dFdCyd produced radiosensitization by potentiating preexisting death pathways,
      then only the apoptotic-prone HT29 cells would show a substantial increase in
      apoptosis when treated with the combination of dFdCyd and radiation and that
      UMSCC-6 cells and A549 cells would be radiosensitized through nonapoptotic
      mechanisms. We found that the radiosensitization of HT29 cells (enhancement
      ratio, 1.81 +/- 0.16) was accompanied by an increase in apoptosis and by caspase
      activation and that inhibition of this activation by the caspase inhibitor Z-Asp
      Glu-Val-Asp-fluoromethylketone (DEVD) significantly decreased radiosensitization
      (to 1.36 +/- 0.24; P < 0.05). In contrast, UMSCC-6 cells and A549 cells were
      modestly radiosensitized (enhancement ratio, 1.47 +/- 0.24 and 1.31 +/- 0.04,
      respectively) via a nonapoptotic mechanism. These findings suggest that although
      apoptosis can contribute significantly to dFdCyd-mediated radiosensitization, the
      role of apoptosis in dFdCyd-mediated radiosensitization depends on the cell line
      rather than representing a general property of the drug.

PMID- 11234887
TI  - Interactions between 2-fluoroadenine 9-beta-D-arabinofuranoside and the kinase
      inhibitor UCN-01 in human leukemia and lymphoma cells.
AB  - Interactions between the purine analogue 2-fluoroadenine 9-beta-D
      arabinofuranoside (F-ara-A) and the kinase inhibitor UCN-01 have been examined in
      human leukemia cells (U937 and HL-60) with respect to induction of mitochondrial
      damage, caspase activation, apoptosis, and loss of clonogenic survival.
      Simultaneous or subsequent exposure of F-ara-A-treated cells (2 microM) to UCN-01
      (100 nM) resulted in a marked potentiation of apoptosis, manifested by loss of
      mitochondrial membrane potential (delta psi(m)), cleavage/activation of
      procaspase-9 and procaspase-3, DNA fragmentation, and degradation of poly
      ADP(ribosyl) polymerase. Coadministration of UCN-01 with F-ara-A was also
      associated with diminished phosphorylation of the cdc25 phosphatase. In contrast,
      exposure of cells to the sequence UCN-01, followed by F-ara-A, resulted in only a
      modest increase in apoptotic cells. The ability of UCN-01 to potentiate F-ara-A
      mediated lethality was not mimicked by the selective PKC inhibitor
      bisindolylmaleimide, nor did treatment of cells with UCN-01 enhance formation of
      F-ara-ATP or increase incorporation of [3H]F-ara-A into DNA. Enhanced apoptosis
      in cells exposed sequentially or simultaneously to F-ara-A and UCN-01 was
      accompanied by a substantial reduction in colony formation (e.g., to 0.01% of
      control values). Cotreatment with UCN-01 also increased F-ara-A-mediated
      apoptosis and loss of delta psi(m) in U937 cells ectopically expressing Bcl-2,
      although not to the same extent as that observed in empty-vector controls.
      Finally, simultaneous exposure (24 h) of malignant B lymphocytes from the pleural
      effusion of a patient with indolent non-Hodgkin's lymphoma to F-ara-A and UCN-01
      ex vivo resulted in a striking increase in apoptosis, as determined by terminal
      deoxynucleotidyltransferase-mediated nick end labeling assay. These findings
      indicate that UCN-01 increases F-ara-A-induced mitochondrial damage and apoptosis
      in human leukemia cells in a sequence-dependent manner, and that these events
      occur in at least some primary human lymphoma cells.

PMID- 11234888
TI  - Activating transcription factor 2-derived peptides alter resistance of human
      tumor cell lines to ultraviolet irradiation and chemical treatment.
AB  - Activating transcription factor 2 (ATF2) and its kinase, p38, play an important
      role in the resistance of melanoma to radiation and chemotherapy. Whereas ATF2 up
      regulates the expression of tumor necrosis factor alpha, which serves as a
      survival factor in late-stage melanoma cells, p38 attenuates Fas expression via
      inhibition of nuclear factor-kappaB. We investigated whether ATF2-derived
      peptides could be used to alter the sensitivity of human melanoma cells to
      radiation and chemical treatment. Of four 50-amino acid peptides tested, the
      peptide spanning amino acids 50-100 elicited the most efficient increase in the
      sensitivity of human melanoma cells to UV radiation or treatment by mitomycin C,
      Adriamycin, and verapamil, or UCN-01, as revealed by apoptosis assays.
      Sensitization by ATF2 peptide was also observed in the MCF7 human breast cancer
      cells but not in early-stage melanoma or melanocytes, or in in vitro-transformed
      293T cells. When combined with an inhibitor of p38 catalytic activity, cells
      expressing amino acids 50-100 of ATF2 exhibited an increase in the degree of
      programmed cell death, indicating that combined targeting of ATF2 and p38 kinases
      is sufficient to induce apoptosis in late-stage melanoma cells. The ability of
      the peptide to increase apoptosis coincided with increased cell surface
      expression of Fas, which is the primary death-signaling cascade in these late
      stage melanoma cells. Overall, our studies identified a critical domain of ATF2
      that may be used to sensitize tumor cells to radiation and chemical treatment
      induced apoptosis and that can induce apoptosis when combined with inhibition of
      ATF2 kinase, p38.

PMID- 11234889
TI  - Possible mechanisms of diarrheal side effects associated with the use of a novel
      chemotherapeutic agent, flavopiridol.
AB  - The novel cyclin-dependent kinase inhibitor flavopiridol has recently completed
      Phase I trials for the treatment of refractory neoplasms. The dose-limiting
      toxicity observed with this agent was severe diarrhea. Because the compound
      otherwise showed promise, the present study sought to determine possible
      mechanisms underlying the diarrheal side effects. Flavopiridol was tested for its
      ability to modify chloride secretory responses of the human colonic epithelial
      cell line, T84. Studies were conducted in vitro in modified Ussing chambers. High
      concentrations of flavopiridol (10(-4) M), above those likely to be clinically
      relevant, had a direct stimulatory effect on chloride secretion, probably
      ascribable to an increase in cyclic AMP. Lower, clinically relevant
      concentrations of flavopiridol (10(-6) M) had no effect on chloride secretion by
      themselves but potentiated responses to the calcium-dependent secretagogue,
      carbachol. The drug also potentiated responses to thapsigargin and
      taurodeoxycholate and reversed the inhibitory effects of carbachol and epidermal
      growth factor on calcium-dependent chloride secretion. Pretreatment with the
      cyclic AMP-dependent secretagogue, forskolin, potentiated responses to
      flavopiridol, but not vice versa. Thus, diarrheal side effects induced by
      flavopiridol are likely multifactorial in origin and may involve interactions
      with endogenous secretagogues such as acetylcholine and bile acids. A better
      understanding of the diarrhea induced by flavopiridol should allow optimization
      of therapy with this otherwise promising drug and/or the development of related
      agents with improved toxicity profiles.

PMID- 11234890
TI  - Cotreatment with STI-571 enhances tumor necrosis factor alpha-related apoptosis
      inducing ligand (TRAIL or apo-2L)-induced apoptosis of Bcr-Abl-positive human
      acute leukemia cells.
AB  - Bcr-Abl tyrosine kinase inhibitor STI-571 induces differentiation and apoptosis
      of HL-60/Bcr-Abl (with ectopic expression of p190 Bcr-Abl) and K562 (with
      endogenous expression of p210 Bcr-Abl) cells (Blood, 96: 2246-2253, 2000).
      Cotreatment with STI-571 partially overcomes the resistance to antileukemic drug
      induced apoptosis of HL-60/Bcr-Abl and K562 cells. Tumor necrosis factor (TNF)
      alpha-related apoptosis-inducing ligand (Apo-2L/TRAIL), after binding with its
      signaling death receptors (DR4 and DR5), triggers the intrinsic "mitochondrial"
      pathway of apoptosis more efficiently in the cancer than do normal cells. In the
      present studies, we compared the apoptotic effects of Apo-2L/TRAIL, with or
      without cotreatment with STI-571, in HL-60/neo, HL-60/Bcr-Abl, and K562 cells. As
      compared with HL-60/neo, HL-60/Bcr-Abl and K562 cells are relatively resistant to
      Apo-2L/TRAIL-induced apoptosis. In HL-60/Bcr-Abl and K562 versus HL-60/neo cells,
      Apo-2L/TRAIL caused less cytosolic accumulation of cytochrome c and the
      processing of caspase-9 and -3. This was also associated with decreased
      processing of caspase-8, c-FLIP(L) and Bid. Reduced effects of Apo-2L/TRAIL in
      Bcr-Abl-positive leukemic cells were not attributable to diminished expression of
      DR4 and DR5, or higher expressions of the decoy receptors DcR1 and -2 or c
      FLIP(L). Cotreatment with STI-571 significantly enhanced Apo-2L/TRAIL-induced
      apoptosis (P < 0.01) as well as increased the processing of caspase-9 and -3 and
      XIAP, without affecting the levels of DR4, DR5, decoy receptors, or c-FLIP(L).
      Cotreatment with STI-571 did not enhance Apo-2L/TRAIL-induced apoptosis of HL
      60/neo cells. These studies suggest that a combined treatment with STI-571 may be
      an effective strategy to selectively sensitize Bcr-Abl-positive leukemic blasts
      to Apo-2L/TRAIL-induced apoptosis.

PMID- 11234891
TI  - Relation between 9-aminocamptothecin systemic exposure and tumor response in
      human solid tumor xenografts.
AB  - 9-Aminocamptothecin (9-AC) is a topoisomerase I inhibitor with activity against
      xenografts from childhood solid tumors; however, clinical trials with this
      compound have been disappointing, resulting in discontinuation of further
      development. The objectives of this study were to evaluate the antitumor activity
      of 9-AC in a panel of pediatric solid tumor xenografts and to relate the 9-AC
      lactone systemic exposure, defined as area under the concentration time curve
      (AUC), to the antitumor dose associated with tumor regression in the xenograft
      model. We evaluated protracted administration of i.v. and oral therapies (daily
      times 5) for 1, 2, or 3 weeks and for 1 or 3 cycles. The minimum effective dose
      of 9-AC causing objective regression of advanced tumors was determined for each
      schedule. 9-AC lactone plasma concentration-time profiles associated with the
      lowest dose achieving complete and partial responses for each xenograft were then
      determined for each regimen. Tumors were highly sensitive to 9-AC therapy, but
      the systemic exposure required for antitumor effect is in excess of that
      achievable in patients.

PMID- 11234892
TI  - Retinoid receptor expression and its correlation to retinoid sensitivity in non
      M3 acute myeloid leukemia blast cells.
AB  - All-trans-retinoic acid (ATRA) has significantly improved the treatment results
      in acute promyelocytic leukemia (M3). In non-M3 acute myeloid leukemia (AML), the
      effects are less clear, and there is a pronounced heterogeneity in the
      sensitivity to the growth-inhibitory effects of retinoids in leukemic cells from
      different non-M3 AML patients. Retinoids exert their effects through a number of
      nuclear receptors [retinoic acid receptors (RARs) and retinoid X receptors
      (RXRs)]. In this study, we determined the expression of RAR alpha, RAR beta, RAR
      gamma, and RXR alpha by real-time PCR in four cell lines and in blast cells from
      patients with non-M3 AML before and after ATRA incubation. All four receptors
      were expressed in cells from all 18 tested patient samples and in four myeloid
      cell lines. In the majority of the patient samples as well as in the cell lines,
      there was a pattern of high expression of RAR alpha and RXR alpha and low
      expression of RAR beta and RAR gamma. There was no correlation between the basal
      expression of any of the retinoid receptors and sensitivity to ATRA. A 24-h
      exposure to ATRA increased the expression of RAR alpha, RAR beta, RAR gamma, and
      RXR alpha in 46%, 77%, 30%, and 38% of the samples, respectively. The mean
      increase in receptor expression was most pronounced for RAR beta and RXR alpha.
      There was a significant correlation between an increase in RAR beta expression in
      response to ATRA and sensitivity to ATRA (P < 0.014). No such correlations were
      found for RAR alpha, RAR gamma, and RXR alpha. The expression of the monocytoid
      marker CD14 was significantly correlated with increased expression of RAR alpha
      (P = 0.03). We conclude that RAR alpha, RAR beta, RAR gamma, and RXR alpha are
      expressed in non-M3 AML blast cells and that ATRA-induced expression of RAR beta
      may be a marker for retinoid sensitivity.

PMID- 11234893
TI  - Preclinical evaluation of motexafin lutetium-mediated intraperitoneal
      photodynamic therapy in a canine model.
AB  - Intraperitoneal photodynamic therapy (IP PDT) is an experimental cancer treatment
      in clinical development for the treatment of peritoneal carcinomatosis and
      sarcomatosis. A canine study of motexafin lutetium (Lu-Tex)-mediated IP PDT was
      performed to evaluate normal tissue toxicities of this treatment in the presence
      and absence of a bowel resection and to assess the feasibility of measuring Lu
      Tex fluorescence in abdominal tissues. Thirteen dogs were treated with Lu-Tex
      (0.2-2 mg/kg) i.v. 3 h before laparotomy and 730-nm light delivery (fluences, 0.5
      2.0 J/cm2; average fluence rate <150 mW/cm2). Laparoscopy was performed 7-10 days
      after the procedure to assess acute toxicities. In situ fluorescence spectra were
      obtained from various abdominal tissues before and after light delivery using a
      fiber array probe with fixed-source detector distances. Lu-Tex-mediated IP PDT
      was well tolerated at the doses of drug and light studied. Bowel toxicity was not
      observed in animals treated with a bowel resection before PDT. Mild transient
      liver function test abnormalities without associated clinical sequelae were
      observed. No gross PDT-related abnormalities were observed at laparoscopy or
      necropsy; however, thickening in the glomerular capillary wall and the mesangium
      were noted microscopically in the kidneys of seven dogs. No renal function
      abnormalities were found. Analysis of the fluorescence spectra from intra
      abdominal tissues suggests that measurements of Lu-Tex in situ are feasible and
      may provide a way of assessing photosensitizer concentration in vivo without the
      need for a biopsy. These results support the continued development of Lu-Tex as a
      candidate photosensitizer for IP PDT.

PMID- 11234894
TI  - Genistein potentiates the radiation effect on prostate carcinoma cells.
AB  - We have shown previously that genistein, the major isoflavone in soybean,
      inhibited the growth of human prostate cancer cells in vitro by affecting the
      cell cycle and inducing apoptosis. To augment the effect of radiation for
      prostate carcinoma, we have now tested the combination of genistein with photon
      and neutron radiation on prostate carcinoma cells in vitro. The effects of photon
      or neutron radiation alone or genistein alone or both combined were evaluated on
      DNA synthesis, cell growth, and cell ability to form colonies. We found that
      neutrons were more effective than photons for the killing of prostate carcinoma
      cells in vitro, resulting in a relative biological effectiveness of 2.6 when
      compared with photons. Genistein at 15 microM caused a significant inhibition in
      DNA synthesis, cell growth, and colony formation in the range of 40-60% and
      potentiated the effect of low doses of 200-300 cGy photon or 100-150 cGy neutron
      radiation. The effect of the combined treatment was more pronounced than with
      genistein or radiation alone. Our data indicate that genistein combined with
      radiation inhibits DNA synthesis, resulting in inhibition of cell division and
      growth. Genistein can augment the effect of neutrons at doses approximately 2
      fold lower than photon doses required to observe the same efficacy. These studies
      suggest a potential of combining genistein with radiation for the treatment of
      localized prostate carcinoma.

PMID- 11234895
TI  - Combination of standard cytotoxic agents with polyamine analogues in the
      treatment of breast cancer cell lines.
AB  - Polyamines are essential for cell growth and differentiation. Structural
      polyamine analogues have been shown to have antitumor activity in experimental
      models including breast cancer. The ability of polyamine analogues to alter
      activity of cytotoxic chemotherapeutic agents in breast cancer models has not
      been evaluated. This study evaluates the ability of two polyamine analogues, N1
      ethyl-N11-[(cyclopropyl)methyl]-4,8-diazaundecane (CPENSpm) and N1-ethyl-N11
      [(cycloheptyl)methyl]-4,8-diazaundecane (CHENSpm) to synergize with cytotoxics in
      five human breast cancer cell lines. Antagonism, additivity, or synergy of the
      combinations was determined using the median effect/combination index model. The
      chemotherapeutic agents chosen, cis-diaminechloroplatinum(II), doxorubicin, 5
      fluorouracil, fluorodeoxyuridine, 4-hydroperoxycyclophosphamide, paclitaxel,
      docetaxel, and vinorelbine, all have antitumor activity in breast cancer and
      represent a spectrum of mechanisms. Three treatment schedules of polyamine
      analogue and cytotoxic were tested in MCF-7 and MDA-MB-468 lines, demonstrating a
      schedule-dependence of synergistic growth inhibition. Cytotoxic agent alone for
      24 h followed by polyamine analogue alone for 96 h resulted in the most
      synergistic combinations and the greatest synergy. This schedule was then tested
      in three additional breast cancer lines, and several synergistic combinations
      were again identified. Two cytotoxics, vinorelbine and the fluoropyrimidines,
      showed the most promise in combination with the polyamine analogues. They were
      able to synergize with one or both polyamine analogues in most of the breast
      cancer cell lines. CPENSpm was also able to synergize with virtually all of the
      cytotoxics in the estrogen receptor alpha-positive MCF-7 and T-47D lines. These
      preclinical data demonstrate a treatment schedule and combinations of polyamine
      analogues and cytotoxics that will be important to study mechanistically and
      clinically for breast cancer.

PMID- 11234896
TI  - Efficacy of treatment with antisense oligonucleotides complementary to
      immunoglobulin sequences of bcl-2/immunoglobulin fusion transcript in a t(14;18)
      human lymphoma-scid mouse model.
AB  - In t(14;18)-positive lymphoma cells, bcl-2 is expressed from a fusion mRNA
      transcript containing the full coding sequence of bcl-2 and 3' immunoglobulin
      sequences. We reported previously that antisense oligodeoxyribonucleotides
      directed at the bcl-2 translational start site, as well as those targeted to
      immunoglobulin sequences 3' of the translocation breakpoint, down-regulate bcl-2
      and inhibit growth of the t(14;18)-positive lymphoma line WSU-FSCCL in vitro. We
      have developed a scid mouse model with this human cell line and demonstrate that
      antisense oligodeoxyribonucleotides targeted to immunoglobulin c(mu) sequences
      down-regulate bcl-2 protein expression and induce apoptosis of WSU-FSCCL cells in
      vivo. This leads to prolonged survival of the mice. Targeting non-oncogenic
      sequences outside of the breakpoints of fusion transcripts may be a clinically
      useful therapeutic strategy.

PMID- 11234897
TI  - Combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
      and actinomycin D induces apoptosis even in TRAIL-resistant human pancreatic
      cancer cells.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a novel member
      of the tumor necrosis factor superfamily of cytokines that induces cell death by
      apoptosis. TRAIL has been shown to be effective in almost two-thirds of solid
      tumors tested thus far, but its effect on pancreatic cancer cells is unknown. We
      tested the effect of TRAIL on seven human pancreatic cancer cell lines (HPAF,
      Panc1, Miapaca2, Bxpc3, Panc89, SW979, and Aspc1) in vitro. Of these cell lines,
      all but Aspc1 showed a significant dose-dependent increase in apoptosis. The
      apoptotic rate, as detected by a terminal deoxynucleotidyl transferase-mediated
      nick end labeling assay, was highest in Bxpc3 (71.5%), followed by HPAF (38.0%),
      Miapaca2 (24.9%), Panc1 (16.1%), Panc89 (15.8%), SW979 (13.9%), and Aspc1 (5.2%).
      Multiple treatments were more effective than a single treatment and caused a
      sustained and profound cell death in all but Aspc1 cells. There was no
      correlation between the effect of TRAIL and the differentiation grade of the cell
      lines, p53 mutation, or bcl-2 or bax expression. The resistance of Aspc1 cells to
      TRAIL was not related to the lack of TRAIL receptors. The combination of
      actinomycin D and TRAIL induced an almost complete lysis of Aspc1 cells, whereas
      actinomycin D alone had no effect on cell survival but inhibited the expression
      of the Flice inhibitory protein, which is assumed to play a role in the apoptotic
      pathway of TRAIL. Thus, the combination of actinomycin D and TRAIL appears to be
      a promising approach for the therapy of pancreatic cancers resistant to TRAIL.

PMID- 11234898
TI  - Tamoxifen modulates apoptotic pathways in primary endometrial cell cultures.
AB  - Clinical data indicate that tamoxifen (TAM) therapy may cause an increased risk
      of endometrial pathology in postmenopausal but not in premenopausal women.
      Molecular mechanisms of the uterotrophic activity of TAM have not been clearly
      established nor its relevance to apoptosis in endometrial cells. The present
      study was implemented to evaluate the apoptotic effect of TAM on primary
      endometrial cell cultures in the presence or absence of steroid hormones (SHs). A
      total of 14 primary endometrial cell cultures were established and maintained
      both with and without SHs. Cell cultures were treated for 24 h with either 20
      microM TAM or 10 nM estradiol. Apoptotic cells presented in a pre-G1 peak and the
      expression of bcl-2 were studied using flow cytometry. All endometrial cell
      cultures maintained in a SH-containing environment, except one, responded to TAM
      by a significant increase (P = 0.03) in the pre-G1 cell fraction, indicating a
      proapoptotic effect. A significant (P = 0.03) reduction in the pre-G1 peak
      equivalent to an antiapoptotic response was observed in 6 of 13 cell cultures
      maintained in a SH-deficient environment. In 4 of 10 cell cultures evaluated in
      both media, the pre-G1 population was medium dependent. In 8 of 10 cultures
      evaluated for Bcl2 levels, no trend was found in either media, but a dependency
      on SH content was observed. Comparison between effects of TAM and estradiol
      demonstrated identical trends, regardless of the menstrual phase or SH content in
      cell environments. These results suggest that TAM acts as an estrogen agonist on
      endometrial tissue in both environments. We conclude that TAM modulates apoptotic
      pathways in primary endometrial cell cultures. The SH content in the cell
      environment influences the apoptotic effect of TAM and determines the propensity
      for a cell to undergo apoptosis or, on the contrary, to resist apoptotic death in
      response to TAM treatment. This is in concordance with the observed clinical risk
      of endometrial pathologies in postmenopausal versus premenopausal women.

PMID- 11234899
TI  - Thresholds of O6-alkylguanine-DNA alkyltransferase which confer significant
      resistance of human glial tumor xenografts to treatment with 1,3-bis(2
      chloroethyl)-1-nitrosourea or temozolomide.
AB  - Bis-2-chloroethylnitrosourea (BCNU) or temozolomide (TMZ) were tested alone or in
      combination with the AGT inhibitors O6-benzyl-2'-deoxyguanosine (dBG) or O6
      benzylguanine (BG) against human glial tumor xenografts growing s.c. in athymic
      mice. Four glioblastoma (SWB77, SWB40, SWB39, and D-54) and one anaplastic
      oligodendroglioma (SWB61) xenografts having O6-alkylguanine-DNA alkyltransferase
      (AGT) activities of 75, 45, 10, < 10, and 16 fmol/mg protein, respectively, were
      used. BCNU at 35 mg/m2 was ineffective against these tumors, although 70 mg/m2
      (LD10, 75 mg/m2) produced a marked tumor growth delay (T-C) in D54 but had no
      effect against SWB40 or SWB77. Coadministration of BG or dBG and BCNU
      necessitated reduction of the BCNU dose to a maximum of 30 and 35 mg/m2,
      respectively, because of increased toxicity. Optimized treatment with dBG (250
      mg/m2) and BCNU (35 mg/m2) resulted in T-Cs of 30, 29, 11, 16, and 14 days for
      SWB77, SWB40, SWB39, D-54 and SWB61, respectively. These delays were more
      pronounced than those induced with optimized, isotoxic treatments with BG (180
      mg/m2) and BCNU (30 mg/m2). In comparison to BCNU, TMZ was less toxic, with an
      LD10 of 400 mg/m2. TMZ (300 mg/m2) was more effective than BCNU against SWB77,
      SWB40, and SWB61, inducing T-Cs of 23, 53, and 56 days, respectively. BG and dBG
      enhanced the toxicity of TMZ in athymic mice by decreasing the LD10 from 400 to
      200 mg/m2. TMZ (180 mg/m2) with either BG (180 mg/m2) or dBG (250 mg/m2) resulted
      in T-Cs of 31 and 49 days in SWB77, respectively, as compared with 16 days for
      TMZ (180 mg/m2) alone. In SWB40, the combination of TMZ with dBG, but not with
      BG, was significantly more effective than the maximum tolerated dose of TMZ (300
      mg/m2) alone. The combination of TMZ with AGT inactivators had no benefit, as
      compared with TMZ alone, against xenografts with marginal AGT activity. In
      conclusion, at equimolar doses dBG was less toxic than BG in athymic mice when
      combined with either BCNU or TMZ. In this regard, BCNU or TMZ can be used at
      higher doses in combination with dBG than with BG. This study further
      demonstrates that there is a significant benefit of depleting AGT with
      nonspecific AGT inhibitors prior to treatment with either BCNU or TMZ in tumors
      having AGT activity >45 fmol/mg protein.

PMID- 11234900
TI  - Cyclooxygenase-2 is overexpressed in human cervical cancer.
AB  - Multiple lines of evidence suggest that cyclooxygenase-2 (COX-2) is an important
      target for preventing epithelial malignancies. Little is known, however, about
      the expression of COX-2 in gynecological malignancies. By immunoblot analysis,
      COX-2 was detected in 12 of 13 cases of cervical cancer but was undetectable in
      normal cervical tissue. Immunohistochemistry revealed COX-2 in malignant
      epithelial cells. COX-2 was also expressed in cervical intraepithelial neoplasia.
      The mechanism by which COX-2 is up-regulated in cervical cancer is unknown.
      Because the epidermal growth factor (EGF) receptor is commonly overexpressed in
      cervical cancer, we investigated whether EGF could induce COX-2 in cultured human
      cervical carcinoma cells. Treatment with EGF markedly induced COX-2 protein, COX
      2 mRNA, and stimulated COX-2 promoter activity. The induction of COX-2 by EGF was
      suppressed by inhibitors of tyrosine kinase activity, phosphatidylinositol 3
      kinase, mitogen-activated protein kinase kinase, and p38 mitogen-activated
      protein kinase. Moreover, overexpressing dominant-negative forms of extracellular
      signal-regulated kinase 1, c-Jun NH2-terminal kinase, p38, and c-Jun blocked EGF
      mediated induction of COX-2 promoter activity. Taken together, these findings
      suggest that deregulation of the EGF receptor signaling pathway may lead to
      enhanced COX-2 expression in cervical cancer.

PMID- 11234901
TI  - Coexpression of proangiogenic factors IL-8 and VEGF by human head and neck
      squamous cell carcinoma involves coactivation by MEK-MAPK and IKK-NF-kappaB
      signal pathways.
AB  - Interleukin 8 (IL-8) and vascular endothelial growth factor (VEGF) promote tumor
      angiogenesis, growth, and metastasis and are coexpressed by human head and neck
      squamous cell carcinomas (HNSCCs) and a variety of other cancers. The promoters
      of the IL-8 and VEGF genes contain different recognition sites for transcription
      factors nuclear factor (NF)-kappaB and activator protein-1 (AP-1), which we
      showed previously are coactivated in HNSCCs. NF-kappaB and AP-1 may be modulated
      by the inhibitor kappaB kinase (IKK) and mitogen-activated protein kinase (MAPK)
      signal pathways, but the contribution of these pathways to expression of IL-8 and
      VEGF and as potential targets for antiangiogenesis therapy in HNSCC is not known.
      In this study, we examined the effects of modulation of the MAPK and IKK pathways
      on expression of IL-8 and VEGF by UM-SCC-9 and UM-SCC-11B cell lines.
      Interruption of IKK-mediated activation of NF-kappaB by expression of an
      inhibitor kappaB alpha mutant (IkappaB alphaM) in UM-SCC-9 cells resulted in
      partial inhibition of expression of IL-8 but not VEGF. Analysis of possible
      alternative pathways for induction of these genes revealed activation of the MAPK
      extracellular signal-regulated kinase (ERK1/2) in cell lines UM-SCC-9 and UM-SCC
      11B. Basal and tumor necrosis factor-alpha-inducible phosphorylation of ERK1/2
      and secretion of IL-8 and VEGF could be specifically inhibited by a MEK
      inhibitor, U0126. Expression of IL-8 and VEGF in the cell lines was associated
      with coactivation of both NF-kappaB and AP-1, and U0126 inhibited both NF-kappaB
      and AP-1 reporter activity in UM-SCC-9 and UM-SCC-11B cells. The ERK pathway
      appears to contribute to expression of IL-8 and VEGF and transactivation of NF
      kappaB as well as AP-1 in HNSCC. Combined inhibition of both MAPK and IKK
      pathways may be needed for suppression of the signal transduction mechanism(s)
      regulating VEGF and IL-8 secretion and angiogenesis by human HNSCC.

PMID- 11234902
TI  - Correspondence re: M.L. George [correction of H.L. George] et al., Correlation of
      plasma and serum vascular endothelial growth factor levels with platelet count in
      colorectal cancer: clinical evidence of platelet scavenging? Clin. Cancer Res.,
      6: 3147-3152, 2000.

PMID- 11234903
TI  - Correspondence re: C. F. M. Sier et al., Enhanced urinary gelatinase activities
      (matrix metalloproteinases 2 and 9) are associated with early-stage bladder
      carcinoma: a comparison with clinically used tumor markers. Clin. Cancer Res., 6:
      2333-2340, 2000.

PMID- 11234904
TI  - Toward an understanding of violence: neurobehavioral aspects of unwarranted
      physical aggression: Aspen Neurobehavioral Conference consensus statement.
AB  - OBJECTIVE: Violence is a global problem that poses a major challenge to
      individuals and society. This document is a consensus statement on
      neurobehavioral aspects of violence as one approach to its understanding and
      control. BACKGROUND: This consensus group was convened under the auspices of the
      Aspen Neurobehavioral Conference, an annual consensus conference devoted to the
      understanding of issues related to mind and brain. The conference is supported by
      the Brain Injury Association and by individual philanthropic contributions.
      Participants were selected by conference organizers to represent leading opinion
      in neurology, neuropsychology, psychiatry, trauma surgery, nursing, evolutionary
      psychology, medical ethics, and law. METHODS: A literature review of the role of
      the brain in violent behavior was conducted and combined with expert opinion from
      the group. The major goal was to survey this field so as to identify major areas
      of interest that could be targeted for further research. Additional review was
      secured from the other attendees at the Aspen Neurobehavioral Conference.
      RESULTS: The group met in the spring of 1998 and 1999 for two 5-day sessions,
      between which individual assignments were carried out. The consensus statement
      was prepared after the second meeting, and agreement on the statement was reached
      by participants after final review of the document. CONCLUSIONS: Violence can
      result from brain dysfunction, although social and evolutionary factors also
      contribute. Study of the neurobehavioral aspects of violence, particularly
      frontal lobe dysfunction, altered serotonin metabolism, and the influence of
      heredity, promises to lead to a deeper understanding of the causes and solution
      of this urgent problem.

PMID- 11234905
TI  - Cognitive correlates of mnemonics usage and verbal recall memory in old age.
AB  - OBJECTIVES: The objectives of this study were to determine whether minimizing
      requisite processing resources to learn a word list would differentially improve
      recall of older adults and to examine the associations between memory and
      nonmemory cognitive abilities. BACKGROUND: It has been hypothesized that a
      reduction in general processing resources contributes to age-related declines in
      memory and other cognitive abilities. METHODS: Twenty-four young adults and 47
      older adults were administered two semantically related word lists, one list with
      words blocked into their categories and the other with categories intermixed.
      Tests of attention and working memory, language, and abstract reasoning were
      interspersed with the memory tasks. Participants were classified as young (age
      range: 17-30 years), young-old (age range: 65-73 years), and old-old (age range:
      74-87 years) to compare the effects of list condition (i.e., blocked vs.
      unblocked) on recall performance. Correlation and regression analyses were used
      to examine the cognitive correlates of recall performance. RESULTS: Expected age
      differences in recall performance were observed. Based on the resource-reduction
      hypothesis of cognitive aging, we hypothesized that the blocked presentation of
      the to-be-remembered list would minimize processing demands and therefore
      differentially benefit recall in older elderly participants. Contrary to our
      prediction, however, the relative benefits of blocked list presentation on recall
      measures were comparable for young and older participants. Correlations and
      regression analyses revealed that recall performance was more strongly associated
      with word finding ability than with working memory or abstract reasoning skills.
      CONCLUSIONS: Results suggest that level of recall of a semantically related word
      list and use of semantic clustering as an encoding strategy are associated more
      strongly with general word finding skills than with processing capacity.

PMID- 11234906
TI  - Obsessivecompulsive disorder and traumatic brain injury: behavioral, cognitive,
      and neuroimaging findings.
AB  - OBJECTIVE: The goal of this study was to evaluate behavior and cognition in a
      consecutive series of patients who developed obsessive-compulsive disorder (OCD)
      after suffering a traumatic brain injury (TBI). BACKGROUND: Because OCD is a rare
      sequelae of TBI, the phenomenology of obsessions and compulsions, the comorbid
      psychiatric disorders, the performance on cognitive tests, and the neural
      correlates have not been well characterized. METHODS: Ten adult patients who met
      DSM-IV diagnostic criteria for OCD after suffering either mild (6 cases),
      moderate (2 cases), or severe (2 cases) TBI were studied using structured
      psychiatric rating scales (i.e., Yale-Brown Obsessive Compulsive Scale),
      cognitive tests, and magnetic resonance imaging (MRI). RESULTS: Global severity
      of OCD ranged from moderate to severe, and all patients had multiple obsessions
      and compulsions. There was a high frequency of aggressive, contamination, need
      for symmetry/exactness, somatic, and sexual obsessions as well as
      cleaning/washing, checking, and repeating compulsions. Unusual features such as
      obsessional slowness (3 cases) and compulsive exercising (3 cases) were also
      documented. Comorbid psychiatric diagnoses were common and included posttraumatic
      stress disorder, anxiety with panic attacks, depression, and intermittent
      explosive disorder. Compared with 10 age-matched normal controls, the OCD group
      had poor performance on tests of general intelligence, attention, learning,
      memory, word-retrieval, and executive functions; these cognitive deficits were
      more pervasive among patients displaying obsessional slowness. All OCD patients
      with mild TBI had normal MRI scans, whereas focal contusions in the
      frontotemporal cortices, subcortical structures (caudate nucleus), or both were
      found in OCD patients with moderate and severe TBI. CONCLUSIONS: Posttraumatic
      OCD has a relatively specific pattern of symptoms even in patients with mild TBI
      and is associated with a variety of other psychiatric disorders, particularly non
      OCD anxiety. The patterns of cognitive deficits and MRI findings suggest
      dysfunction of frontal-subcortical circuits.

PMID- 11234907
TI  - A comparison of memory performance in relapsing-remitting, primary progressive
      and secondary progressive, multiple sclerosis.
AB  - OBJECTIVE: The current investigation was designed to examine the influence of
      disease course on the specific patterns of acquisition and retrieval impairments
      in multiple sclerosis (MS). BACKGROUND: Recent investigations of learning and
      memory in MS have shown that many subjects have impaired verbal and visual new
      learning abilities, but normal long-term recall and recognition. However,
      heterogeneity in the learning and memory abilities of subjects has been
      documented. Some evidence in the literature suggests that this heterogeneity may
      be in part attributable to clinical variables, such as disease course. METHODS:
      Verbal and visual learning and memory tests, modified to equate MS groups with
      healthy controls on initial acquisition of information, were administered to 64
      individuals with clinically definite MS (relapse-remitting = 21; primary
      progressive = 18; secondary progressive = 25), and to 20 healthy control
      participants. Recall and recognition performance then was evaluated at 30
      minutes, at 90 minutes, and at 1 week for the verbal learning task, and at 30
      minutes and at 90 minutes for the visual learning task. RESULTS: Results indicate
      that the two progressive forms of MS result in significantly greater deficits in
      regard to the acquisition of new verbal information, with the secondary
      progressive group showing a significantly higher failure rate in regard to
      meeting the learning criterion. Performance for recognition measures was not
      significantly different among groups, whereas recall performance of the primary
      progressive group was significantly below that of the control group and of the
      secondary progressive group. When testing new learning with visuospatial
      information, individuals with relapse-remitting MS and secondary progressive MS
      required more trials than control participants to learn the same amount of visual
      information. Visual recall and recognition performance did not differ between
      groups. No group differences in rates of forgetting for visuospatial material was
      observed after equating for acquisition. CONCLUSIONS: Results of the current
      study indicate that the primary problem in MS with regard to memory functioning
      is in the acquisition of new information. Our findings support previous research
      showing verbal memory deficits with a progressive disease course and visuospatial
      memory deficits in relapse-remitting MS. However, the detailed analysis of new
      learning and memory performed in the current study indicated that the primary
      progressive group may be showing difficulty in their ability to use newly learned
      information. The pattern of new learning deficits observed between MS disease
      subtypes in the current study was determined to be unrelated to the duration of
      MS and to the physical severity of the disease. The degree of physical disability
      observed in patients with MS does not appear to be related to the degree of
      cognitive decline because of the distinct patterns and severity of memory
      dysfunction noted within each disease type, independent of physical disability.

PMID- 11234908
TI  - Ideomotor apraxia in patients with Alzheimer disease: why do they use their body
      parts as objects?
AB  - OBJECTIVE: Difficulty in pantomiming the use of tools is observed in patients
      with Alzheimer disease. Patients with Alzheimer disease tend to use their body
      parts as objects when they try to pantomime the use of tools. The body-parts-as
      objects phenomenon was thought to consist of appropriate gross movement of
      patients' arms despite inappropriate patterns of handling tools with their hands.
      However, the mechanism has not been investigated fully. METHODS: The authors
      examined 11 healthy individuals and 24 patients with Alzheimer disease for
      ability to recognize tools, to pantomime the use of tools, to use actual tools,
      and to select an appropriate photograph of a handling pattern of the tool.
      RESULTS: In comparison with the patients with Alzheimer disease, the healthy
      individuals had higher scores for all tasks. The authors classified the patients
      into group A (patients with higher pantomime scores), group B (patients with
      middle level scores), and group C (patients with lower scores). Frequency of use
      of body parts as objects for patients in group B was higher than that of patients
      in group A and in group C. The mean Mini-Mental State Examination score for
      patients in group A was higher than that of patients in group B and in group C.
      In comparison with patients in group A, patients in group B showed lower scores
      on the hand-posture discrimination task without a tool, even after controlling
      the Mini-Mental State Examination score. CONCLUSIONS: The authors conclude that
      body-parts-as-objects responses in patients with Alzheimer disease occur because
      general cognition is lowered or because retrieval ability of the appropriate
      holding posture for tools is impaired.

PMID- 11234909
TI  - The effects of vagus nerve stimulation on cognitive performance in patients with
      treatment-resistant depression.
AB  - BACKGROUND: Chronic vagus nerve stimulation (VNS) is effective in the management
      of treatment-resistant epilepsy. Open-trial evidence suggests that VNS has
      clinically significant antidepressant effects in some individuals who experience
      treatment-resistant major depressive episodes. However, limited information
      regarding the effects of VNS on neurocognitive performance exists. OBJECTIVE: The
      primary aim of this study was to determine whether VNS leads to neurocognitive
      deterioration. METHOD: A neuropsychological battery was administered to 27
      patients with treatment-resistant depression before and after 10 weeks of VNS.
      Thirteen neurocognitive tests sampled the domains of motor speed, psychomotor
      function, language, attention, memory, and executive function. RESULTS: No
      evidence of deterioration in any neurocognitive measure was detected. Relative to
      baseline, improvement in motor speed (finger tapping), psychomotor function
      (digit-symbol test), language (verbal fluency), and executive functions (logical
      reasoning, working memory, response inhibition, or impulsiveness) was found. For
      some measures, improved neurocognitive performance correlated with the extent of
      reduction in depressive symptoms, but VNS output current was not related to
      changes in cognitive performance. CONCLUSIONS: Vagus nerve stimulation in
      treatment-resistant depression may result in enhanced neurocognitive function,
      primarily among patients who show clinical improvement. Controlled investigation
      is needed to rule out the contribution of practice effects.

PMID- 11234910
TI  - Cognitive and metabolic responses to metrifonate therapy in Alzheimer disease.
AB  - OBJECTIVE: The objective of this study was to identify the relation between the
      cognitive benefit seen with the cholinesterase inhibitor metrifonate and changes
      in brain metabolism as visualized with [18F]-fluorodeoxyglucose positron emission
      tomography (FDG-PET). BACKGROUND: The regional metabolic correlates of treatment
      with cholinesterase inhibitors are poorly understood. METHODS: Six patients with
      mild to moderate Alzheimer disease (AD) were evaluated before and after treatment
      with the long-lasting cholinesterase inhibitor metrifonate. Patients were given
      60 or 80 mg of metrifonate per day (based on weight) for 6 to 12 weeks. Clinical
      evaluations included the cognitive portion of the Alzheimer's Disease Assessment
      Scale (ADAS-cog), the Mini-Mental State Examination (MMSE), and the
      Neuropsychiatric Inventory. Imaging was carried out using FDG-PET. The PET
      studies, registered to a probabilistic anatomic atlas, were normalized across the
      group's mean intensity levels and subjected to voxel-by-voxel subtraction of the
      posttreatment minus pretreatment studies. Subvolume thresholding corrected random
      lobar noise to produce a three-dimensional functional significance map. RESULTS:
      The criteria for cognitive improvement with treatment were met for the MMSE (>2
      points improvement from baseline), and the drawing subscale of the ADAS-cog was
      significantly improved with treatment. The three-dimensional significance map
      revealed a significant metabolic increase of the dorsolateral frontoparietal
      network on the left and bilateral temporal cortex with metrifonate treatment.
      CONCLUSION: The clinical benefits observed in AD with cholinesterase inhibitor
      therapy are associated with a metabolic increase of heteromodal cognitive and
      medial temporal networks.

PMID- 11234911
TI  - Short-term effects of olanzapine in Huntington disease.
AB  - OBJECTIVE: The aim was to describe the short-term (6 months) effects of
      olanzapine on behavioral and motor clinical manifestations in a group of 11
      patients with Huntington disease. METHOD: An open-pilot study of olanzapine (5
      mg) in patients with clinical and genetic diagnosis of Huntington disease was
      used. The Unified Huntington Disease Rating Scale for clinical assessment and the
      Total Functional Capacity score for the disease-stage evaluation were used. A
      statistical analysis was performed to compare the effects of olanzapine on the
      Unified Huntington Disease Rating Scale scores at time 0 (baseline) and at time 1
      (6 months). Comparisons of motor scores, of single behavioral items, and of TFC
      scores were performed within the group. RESULTS: The behavioral assessment score
      of items regarding depression, anxiety, irritability, and obsessions showed a
      significant improvement (range of p, 0.0134-0.048). Given the total behavioral
      scores (sum of all the items investigated), five patients significantly improved
      their behavioral score after a 6-month treatment (range of p, 0.013-0.047).
      Choreic movements improved, although not significantly (0.05 < or = p < or = 1).
      CONCLUSIONS: Olanzapine is a potentially useful antipsychotic drug, with
      significant short-term effects on behavioral changes, mainly in patients with
      severe psychiatric symptoms at the onset. It might be considered as a possible
      therapeutic choice for treatment of Huntington disease.

PMID- 11234912
TI  - Kleptomania in a patient with a right frontolimbic lesion.
AB  - OBJECTIVE: The authors report the case of a patient in whom kleptomania developed
      in the course of a right frontolimbic behavior syndrome after undergoing surgery.
      BACKGROUND: Kleptomania is a behavior abnormality that is classified as an
      impulse-control disorder; however, little is known about its organic correlates.
      METHOD: History included neurologic data, neuropsychological data,
      electroencephalographic data, and magnetic resonance images. RESULTS: Observation
      of kleptomania associated with a large sellar craniopharyngioma with right-sided
      extension suggests that the site of a lesion may be crucial for the development
      of an impulse-control disorder. CONCLUSIONS: The authors discuss kleptomania in
      the context of functional deficits associated with damage to orbitofrontal
      subcortical circuits, and they suggest that kleptomania is a neuropsychiatric
      symptom that can be conceptualized as being an uncommon compulsive display of
      impulse dyscontrol.

PMID- 11234913
TI  - Determination of folate derivatives in rat tissues during folate deficiency.
AB  - A method for the sensitive and specific determination of folate derivatives was
      developed. The method involves hydrolysis by gamma-glutamyl hydrolase and high
      performance liquid chromatography with electrochemical detection. The method was
      applied to measure the change in the level of folate derivatives in the liver,
      kidney, spleen and brain of rats during folate deficiency. 5,6,7,8
      Tetrahydrofolic acid was the major folate derivative in the liver, kidney, spleen
      and brain. Total concentration of folate derivatives decreased from the second
      week of folate deficiency in the liver, kidney, spleen and brain followed by
      anemia, which appeared at the fifth week. The level of 5,6,7,8-tetrahydrofolic
      acid in the brain did not change during folate deficiency, but it significantly
      decreased in the liver, kidney and spleen.

PMID- 11234914
TI  - Metabolism of [3alpha-3H] 25-hydroxyvitamin D2 in kidneys isolated from normal
      and vitamin D2-intoxicated rats.
AB  - With the availability of A-ring labelled 25OHD2, [3alpha-3H] 25OHD2, we have
      performed the present study to examine the metabolism of 25OHD2 using
      physiological substrate concentrations in perfused kidneys isolated from both
      normal and vitamin D2-intoxicated rats. Our results indicate that [3alpha-3H]
      25OHD2 is metabolized into both 24(S),25,28-trihydroxyvitamin D2
      [24(S),25,28(OH)3D2] and 24(R),25,26-trihydroxyvitamin D2 [24(R), 25,26(OH)3D2],
      and the amounts of these two metabolites produced in the kidney of vitamin D2
      intoxicated rat were about 3-5 times higher than those produced in the kidney of
      normal rat. Similar results were also obtained with rat kidney homogenates
      incubated with [3alpha-3H] 25OHD2. Furthermore, we noted that the production of
      both 24(S),25,28(OH)3D2 and 24(R),25,26(OH)3D2 in the kidney homogenates of
      vitamin D2-intoxicated rats increased with the time of incubation and then
      subsequently decreased. The decrease in both 24(S),25,28(OH)3D2 and
      24(R),25,26(OH)3D2 coincided with an increase in the fraction of total
      radioactivity distributed in the aqueous phase of the kidney homogenates. This
      finding suggested the possibility of further metabolism of 24(S),25,28(OH)3D2 and
      24(R), 25,26(OH)3D2 into polar water-soluble metabolite(s). We then measured the
      radioactivity in the aqueous phase of kidney homogenates of both normal and
      vitamin D2-intoxicated rats incubated with [3alpha-3H] 25OHD2. It was noted that
      the amount of radioactivity in the aqueous phase of kidney homogenates of vitamin
      D2-intoxicated rats is higher than that present in the aqueous phase of kidney
      homogenates of normal rats. Thus, our study provides evidence for the first time
      for the formation of both 24(S),25,28(OH)3D2 and 24(R),25, 26(OH)3D2 under
      physiological conditions, and the possibility of their further metabolism into as
      yet unidentified polar water-soluble metabolite(s). As the formation of all these
      metabolites is increased in the kidney of vitamin D2-intoxicated rats when
      compared to normal rats, it appears that the increased rate of metabolism of
      25OHD2 during hypervitaminosis D2 plays a significant role in the deactivation of
      25OHD2.

PMID- 11234915
TI  - Suppressive effect of curcumin on trichloroethylene-induced oxidative stress.
AB  - In vivo antioxidative effects of curcumin were investigated using a
      trichloroethylene (TCE)-induced oxidative stress model in mouse liver. Increases
      in the contents of peroxisome and thiobarbituric acid reactive substances (TBARS)
      and decreases in GSH content of mouse liver by the TCE administration were
      suppressed by the pre-administration of curcumin. TCE-induced changes in the
      activities of antioxidative enzyme, such as Cu/Zn-SOD, catalase, glutathione
      reductase. glutathione peroxidase (GPx) and D-glucose-6-phosphate dehydrogenase
      (G6PD), were also diminished by curcumin. These results indicate that curcumin
      significantly suppresses TCE-induced oxidative stress by scavenging various free
      radicals, and its antioxidative activity seems to be derived from its suppressive
      effects on the increase in peroxisome content and decrease in GPx and G6PD
      activities.

PMID- 11234916
TI  - Increased cholesterol absorption by hyperlipidemia atherosclerosis prone (LAP)
      Japanese quail.
AB  - The present study describes the cholesterol absorption by hyperlipidemia
      atherosclerosis prone (LAP) Japanese quail to address their high susceptibility
      to experimental atherosclerosis. The apparent cholesterol absorption rate of LAP
      quail was compared with that of commercially available (CA) Japanese quail. After
      14 d of cholesterol feeding by gavage, it was found that the cholesterol
      excretion of LAP quail was significantly lower than that of CA quail. The fecal
      excretion of bile acid and fat showed a similar tendency to that as shown with
      the case of cholesterol. The cholesterol feeding only increased the serum
      cholesterol level of LAP quail, and this trend holds true for the liver lipid
      concentration. The expression level of liver cholesterol 7alpha-hydroxylase mRNA
      showed no difference between LAP and CA strains under the conditions of
      cholesterol loading. These results showed that the cholesterol absorption by LAP
      quail is significantly higher than that by CA quail, which may reasonably explain
      the higher susceptibility of this strain to experimental atherosclerosis.

PMID- 11234917
TI  - Forms of cytochrome P450 in the liver microsome of oxidized frying oil-fed guinea
      pigs.
AB  - The aim of this study is to investigate the influence of oxidized frying oil
      (OFO) on the induction of individual forms of cytochrome P450 (CYP450) in guinea
      pigs. The OFO samples were obtained by frying potato chips in soybean oil at
      200+/-5 degrees C for 24 h. Sixteen male weaning guinea pigs were fed for 12 wk
      on a diet which included 15% of either OFO or fresh soybean oil supplemented with
      300 ppm ascorbic acid. It was demonstrated that guinea pigs fed with the OFO diet
      (D300) exhibited inferior growth rates and lower feed efficiency than the control
      group (F300). The vitamin C contents of plasma, liver, and kidney in the D300
      group were lower than those in the F300 group. Further, the thiobarbituric acid
      reactive substance content in D300 liver and kidney was higher than that in the
      F300 equivalent. The liver UDP-glucuronyl-transferase activity in the D300 group
      was higher than that in the F300 group, and there was no difference in comparing
      the glutathione-S-transferase activity levels of the two groups. Notably, the
      total CYP450 content and the NADPH-cytochrome c reductase activity were
      significantly elevated in the D300 group. The ethoxyresorufin O-deethylase
      activity, which mainly represents CYP1A1 activity, for the detection of CYP450
      isozyme characteristics was elevated more in the D300 than in the F300 group.
      There was no difference in the pentoxyresorufin O-dealkylase activity, which
      mainly reflects the CYP2B isozyme, between the two groups. However, the quantity
      of CYP1A1 isoform determined in the D300 group did not differ from that in the
      F300 group, as revealed by SDS-PAGE and Western blot testing. Our results
      demonstrate that the relative enzyme activity to CYP1A1-like activity of the
      guinea pig hepatic xenobiotic metabolizing enzyme system may be induced by OFO
      feeding, but more advanced research is needed to identify the predominant form of
      CYP450 isozyme induced as a result of this condition.

PMID- 11234918
TI  - Crude protein content and amino acid composition in Taiwanese human milk.
AB  - Breast milk provides the essential nutrients for infants in readily available
      form. The content of nitrogen in human milk is of great importance because it
      relates to the growth of infants in the early stage, and the composition of
      nitrogenated compounds varies according to the lactational stage. Three-hundred
      and-three human milk specimens were obtained from 240 healthy mothers living in
      two different districts in Taiwan, and 264 specimens were used for the analysis.
      The crude protein content, total and free amino acid compositions as well as urea
      content were evaluated using pooled milk samples according to different
      lactational stages and geographical location. The crude protein content decreased
      sharply from colostrum (2.51 g/100 mL) to mature milk (1.25 g/100 mL). Total
      amino acids account for 80-85% of the crude protein throughout the whole
      lactation period. Crude protein also contained 30 to 35 mg/ 100 mL urea and 41 to
      48 mg/ 100 mL free amino acids as non-protein nitrogen components. The ratio of
      essential to non-essential amino acids remained constant throughout the lactation
      period in spite of a decline in amino acid content. The amino acid composition
      per 1 g of nitrogen varied during the lactation period. The differences of these
      lactational changing patterns of individual amino acids were probably reflected
      by variation of the protein composition during lactation. The sum of free amino
      acid content ranged from 43 to 50 mg/100 mL in Taipei and 40 to 45 mg/100 ml, in
      Kaohsiung. Although the variations of free amino acids during the lactation
      period differed among amino acids, glutamic acid predominated in mature milk
      while phosphoethanolamine was predominant in colostrum.

PMID- 11234919
TI  - Effect of phospholipids transesterified enzymatically with polyunsaturated fatty
      acids on gelatinization and retrogradation of starch.
AB  - The effects of phospholipids (PLs) transesterified with polyunsaturated fatty
      acids (PUFAs) with lipase (Aspergillus niger) on gelatinization and
      retrogradation of starch during storage were studied by differential scanning
      calorimetry (DSC). The resulting transesterified PLs were rich in PUFAs and
      linoleic acid, while the total percentage of PUFAs incorporated was 20.2%. The
      addition of PLs or PLs enzymatically transesterified with PUFAs (PUFA-PLs) to the
      starch sample decreased the gelatinization enthalpy of starch (deltah(g))
      slightly, but clearly increased the starch-lipid complexes (deltah(s-1)) by DSC.
      After 21 days of storage, the percent of retrogradation of starch became lower by
      the addition of 4%, PLs or 4% PUFA-PLs to the starch sample when compared with
      the control. These results suggest that PLs retard retrogradation of starch
      during storage, whereas PUFA-PLs retard it greatly. The addition of PLs or PUFA
      PLs increased the amount of deltah(s-1), while re-gelatinization enthalpy
      decreased during storage, which suggests that PLs or PUFA-PLs could retard the
      retrogradation of starch.

PMID- 11234920
TI  - Clinical and analytical evaluation of the simultaneous HPLC assay of retinol and
      alpha-tocopherol.
AB  - We describe a method for the simultaneous assay of retinol and alpha-tocopherol
      using normal-phase, high-performance liquid chromatography (HPLC). Our normal
      phase HPLC method gave better resolution (Rs) of retinol (Rs= 1.58) and alpha
      tocopherol (Rs = 1.40) when compared with the Rs values for a-tocopherol and
      retinol from literature. Also, the alpha-tocopherol concentrations obtained by
      our method agreed well with another normal-phase HPLC method that used
      fluorometric detection (r = 0.951, p<0.001. Sy.x=0.58 mg/L). The concentrations
      of retinol in our method agreed well with those determined by a reversed-phase
      HPLC procedure, although the correlation (r=0.646, p<.001, Sy.x=62 microg/L) was
      not as good as the method proposed. Our procedure gave acceptable precision: the
      within-run CV was 7.7% for alpha-tocopherol and 5.9% for retinol. The between-day
      CV was 9.0% for alpha-tocopherol and 6.8% for retinol. The mean recoveries were
      97% for alpha-tocopherol and 107% for retinol. Our assays were linear for alpha
      tocopherol concentrations from 0.1 to 30 mg/L and for retinol concentrations from
      20 to 2,000 microg/L. In children ages 7 to 12 y, and in adolescents ages 14 to
      16 y, the alpha-tocopherol and retinol concentrations in the blood were
      significantly lower than the concentrations in normal adults. Individuals over 70
      y old also showed alpha-tocopherol and retinol values that were lower than those
      of normal adults between ages 30 and 40 y. In female university students, the
      inter-individual variation of alpha-tocopherol was reduced by dividing the alpha
      tocopherol results by their total cholesterol or total lipid concentrations;
      however, this was not obtained for retinol. In cancer patients undergoing
      surgery, the ratio of retinol to retinol-binding protein (RBP) remained fairly
      constant, although the concentrations of both retinol and RBP decreased to about
      one-half the preoperative values after surgery. We conclude that our normal-phase
      HPLC method is a stable and reproducible method for alpha-tocopherol and retinol,
      and is an easy-to-use analytical tool.

PMID- 11234921
TI  - Beta-carotene 15,15'-dioxygenase activity in streptozotocin-induced diabetic
      rats.
AB  - We measured retinol levels and beta-carotene 15,15'-dioxygenase activity in rats
      with streptozotocin-induced diabetes mellitus to assess the relationship between
      the disease and the conversion of beta-carotene to retinol. The plasma retinol
      level was significantly lower in diabetic rats than in control rats, but the
      hepatic retinol level was significantly higher than the control. The hepatic
      dioxygenase activity, but not that of the intestinal mucosa, was significantly
      lower in diabetic rats than in control rats. The hepatic dioxygenase activity
      showed a significant negative correlation with the hepatic retinol levels. The
      results suggest the disturbed secretion of retinol from the liver and suppression
      of hepatic dioxygenase activity by the retinol increased in the liver in diabetic
      rats.

PMID- 11234922
TI  - Heat stability of proton behaviors for dietary fiber in water on spin-spin
      relaxation measured by 1H-NMR.
AB  - The proton relaxation behavior of dietary fibers on 1H-NMR was investigated with
      water systems before and after heat treatment at 85 degrees C for 30 min. Quite
      similar spin-spin relaxation curves were observed for dietary fibers except agar
      with or without heat treatment in the water system. The relaxation times for the
      fast and slow components and proton populations for the two components were
      analyzed to evaluate interaction between dietary fiber and water more precisely.
      As a result, it turned out that there was little variation in the relaxation time
      and the proton population before and after heat treatment as well. Therefore,
      most dietary fibers were inferred to be heat-stable in respect of proton exchange
      for water.

PMID- 11234923
TI  - The role of RNA stability during bacterial stress responses and starvation.

PMID- 11234924
TI  - Horizontal transfer of an exopolymer complex from one bacterial species to
      another.
AB  - Alasan, the exocellular polymeric emulsifier produced by Acinetobacter
      radioresistens KA53 was shown to bind to the surface of Sphingomonas paucimobilis
      EPA505 and Acinetobacter calcoaceticus RAG-1. The presence of alasan on the
      surface of S. paucimobilis EPA505 and A. calcoaceticus RAG-1 caused a decrease in
      their cell-surface hydrophobicities. Binding was proportional to the
      concentration of recipient cells and input alasan. At the highest concentration
      of A. calcoaceticus RAG-1 (4 x 10(9) ml(-1)) and alasan (20 microg ml(-1))
      tested, 75% of the alasan was cell bound. Alasan binding was measured by the loss
      of emulsifying activity and alasan protein and polysaccharide from the aqueous
      phase after incubation of alasan with the recipient cells. In addition, alasan
      was visualized on the surface of the recipient cells by staining with anti-alasan
      antibodies and rhodamine-labelled secondary antibodies. Moreover, when the alasan
      producing A. radioresistens KA53 was grown together with A. calcoaceticus RAG-1,
      alasan was released from the producing strain and became bound to the recipient
      RAG-1 cells, as demonstrated by fluorescence microscopy. This horizontal transfer
      of exopolymers from one bacterial species to another has significant implications
      in natural microbial communities, coaggregation and biofilms.

PMID- 11234925
TI  - Cadmium-regulated gene fusions in Pseudomonas fluorescens.
AB  - To study the mechanisms soil bacteria use to cope with elevated concentrations of
      heavy metals in the environment, a mutagenesis with the lacZ-based reporter gene
      transposon Tn5B20 was performed. Random gene fusions in the genome of the common
      soil bacterium Pseudomonas fluorescens strain ATCC 13525 were used to create a
      bank of 5,000 P. fluorescens mutants. This mutant bank was screened for
      differential gene expression in the presence of the toxic metal cadmium. Fourteen
      mutants were identified that responded with increased or reduced gene expression
      to the presence of cadmium. The mutants were characterized with respect to their
      metal-dependent gene expression and their metal tolerance. Half the identified
      mutants reacted with differential gene expression specifically to the metal
      cadmium, whereas some of the other mutants also responded to elevated
      concentrations of copper and zinc ions. One of the mutants, strain C8, also
      showed increased gene expression in the presence of the solvent ethanol, but
      otherwise no overlap between cadmium-induced gene expression and general stress
      response was detected. Molecular analysis of the corresponding genetic loci was
      performed using arbitrary polymerase chain reaction (PCR), DNA sequencing and
      comparison of the deduced protein products with sequences deposited in genetic
      databases. Some of the genetic loci targeted by the transposon did not show any
      similarities to any known genes; thus, they may represent 'novel' loci. The
      hypothesis that genes that are differentially expressed in the presence of heavy
      metals play a role in metal tolerance was verified for one of the mutants. This
      mutant, strain C11, was hypersensitive to cadmium and zinc ions. In mutant C11,
      the transposon had inserted into a genetic region displaying similarity to genes
      encoding the sensor/regulator protein pairs of two-component systems that
      regulate gene expression in metal-resistant bacteria, including czcRS of
      Ralstonia eutropha, czrRS of Pseudomonas aeruginosa and copRS of Pseudomonas
      syringae. Although the P. fluorescens strain used in this study had not been
      isolated from a metal-rich environment, it nevertheless contained at least one
      genetic region enabling it to cope with elevated concentrations of heavy metals.

PMID- 11234926
TI  - Remarkably low temperature optima for extracellular enzyme activity from Arctic
      bacteria and sea ice.
AB  - Extracellular degradative enzymes released by psychrophilic marine bacteria
      (growing optimally at or below 15 degrees C and maximally at 20 degrees C)
      typically express activity optima at temperatures well above the upper growth
      limit of the producing strain. In the present study, we investigated whether or
      not near-zero Arctic environments contain extracellular enzymes with activity
      optimized to temperatures lower than previously reported. By applying
      fluorescently tagged substrate analogues to measure leucine-aminopeptidase and
      chitobiase activity, the occurrence of extracellular enzymatic activity (EEA)
      with remarkably low temperature optima (15 degrees C) was documented in sea-ice
      samples. An extremely psychrophilic bacterial isolate, strain 34H, yielded an
      extract of cell-free protease with activity optimized at 20 degrees C, the lowest
      optimum yet reported for cell-free EEA from a pure culture. The use of zymogram
      gels revealed the presence of three proteolytic bands (between 37 and 45 kDa) in
      the extract and the release of the greatest quantities of the proteases when the
      strain was grown at -1 degrees C, suggesting a bacterial strategy for
      counteracting the effects of very cold temperatures on the catalytic efficiency
      of released enzymes. The detection of unusually cold-adapted EEA in environmental
      samples has ramifications not only to polar ecosystems and carbon cycling but
      also to protein evolution, biotechnology and bioremediation.

PMID- 11234927
TI  - Studies on the in situ physiology of Thiothrix spp. present in activated sludge.
AB  - The in situ physiology of the filamentous sulphur bacterium Thiothrix spp. was
      investigated in an industrial wastewater treatment plant with severe bulking
      problems as a result of overgrowth of Thiothrix. Identification and enumeration
      using fluorescence in situ hybridization (FISH) with species-specific 16S and 23S
      rRNA probes revealed that 5-10% of the bacteria in the activated sludge were
      Thiothrix spp. By using a combination of FISH and microautoradiography it was
      possible to study the in situ physiology of probe-defined Thiothrix filaments
      under different environmental conditions. The Thiothrix filaments were very
      versatile and showed incorporation of radiolabelled acetate and/or bicarbonate
      under heterotrophic, mixotrophic and chemolithoautotrophic conditions. The
      Thiothrix filaments were active under anaerobic conditions (with or without
      nitrate) in which intracellular sulphur globules were formed from thiosulphate
      and acetate was taken up. Thiothrix-specific substrate uptake rates and growth
      rates in activated sludge samples were determined under different conditions.
      Doubling times of 6-9 h under mixotrophic conditions and 15-30 h under
      autotrophic conditions were estimated. The key properties that Thiothrix might be
      employing to outcompete other microorganisms in activated sludge were probably
      related to the mixotrophic growth potential with strong stimulation of acetate
      uptake by thiosulphate, as well as stimulation of bicarbonate incorporation by
      acetate in the presence of thiosulphate.

PMID- 11234928
TI  - Anaerobic respiratory growth of Vibrio harveyi, Vibrio fischeri and
      Photobacterium leiognathi with trimethylamine N-oxide, nitrate and fumarate:
      ecological implications.
AB  - Two symbiotic species, Photobacterium leiognathi and Vibrio fischeri, and one non
      symbiotic species, Vibrio harveyi, of the Vibrionaceae were tested for their
      ability to grow by anaerobic respiration on various electron acceptors, including
      trimethylamine N-oxide (TMAO) and dimethylsulphoxide (DMSO), compounds common in
      the marine environment. Each species was able to grow anaerobically with TMAO,
      nitrate or fumarate, but not with DMSO, as an electron acceptor. Cell growth
      under microaerophilic growth conditions resulted in elevated levels of TMAO
      reductase, nitrate reductase and fumarate reductase activity in each strain,
      whereas growth in the presence of the respective substrate for each enzyme
      further elevated enzyme activity. TMAO reductase specific activity was the
      highest of all the reductases. Interestingly, the bacteria-colonized light organs
      from the two squids, Euprymna scolopes and Euprymna morsei, and the light organ
      of the ponyfish, Leiognathus equus, also had high levels of TMAO reductase enzyme
      activity, in contrast to non-symbiotic tissues. The ability of these bacterial
      symbionts to support cell growth by respiration with TMAO may conceivably
      eliminate the competition for oxygen needed for both bioluminescence and
      metabolism.

PMID- 11234929
TI  - A Pseudomonas stutzeri gene cluster encoding the biosynthesis of the CCl4
      dechlorination agent pyridine-2,6-bis(thiocarboxylic acid).
AB  - A spontaneous mutant of Pseudomonas stutzeri strain KC lacked the carbon
      tetrachloride (CCl4) transformation ability of wild-type KC. Analysis of
      restriction digests separated by pulsed-field gel electrophoresis (PFGE)
      indicated that the mutant strain CTN1 differed from strain KC by deletion of
      approximately 170 kb of chromosomal DNA. CTN1 did not produce pyridine-2,6
      bis(thiocarboxylic acid) (PDTC), the agent determined to be responsible for CCl4
      dechlorination in cultures of strain KC. Cosmids from a genomic library of strain
      KC containing DNA from within the deleted region were identified by hybridization
      with a 148 kb genomic Spel fragment absent in strain CTN1. Several cosmids
      identified in this manner were further screened for complementation of the PDTC
      biosynthesis-negative (Pdt -) phenotype. One cosmid (pT31) complemented the Pdt-
      phenotype of CTN1 and conferred CCl4 transformation activity and PDTC production
      upon other pseudomonads. Southern analysis showed that none of three other P.
      stutzeri strains representing three genomovars contained DNA that would hybridize
      with the 25,746 bp insert of pT31. Transposon mutagenesis of pT31 identified open
      reading frames (ORFs) whose disruption affected the ability to make PDTC in the
      strain CTN1 background. These data describe the pdt locus of strain KC as
      residing in a non-essential region of the chromosome subject to spontaneous
      deletion. The pdt locus is necessary for PDTC biosynthesis in strain KC and is
      sufficient for PDTC biosynthesis by other pseudomonads but is not a common
      feature of P. stutzeri strains.

PMID- 11234930
TI  - Detection of abundant sulphate-reducing bacteria in marine oxic sediment layers
      by a combined cultivation and molecular approach.
AB  - The depth distribution and diversity of sulphate-reducing bacteria (SRB) was
      analysed in the upper intertidal zone of a sandy marine sediment of the Dutch
      island Schiermonnikoog. The upper centimetre of the sediment included the oxic
      anoxic interface and was cut into five slices. With each slice, most probable
      number (MPN) dilution series were set up in microtitre plates using five
      different substrates. In the deeper sediment layers, up to 1 x 10(8) cm(-3)
      lactate-utilizing SRB were counted, corresponding to 23% of the total bacterial
      count. From the highest positive dilutions of the MPN series, 27 strains of SRB
      were isolated in pure culture. Sequencing of a 580 bp fragment of the 16S rDNA
      revealed that 21 isolates had identical sequences, also identical with that of
      the previously described species Desulfomicrobium apsheronum. However, the
      diversity of the isolates was higher with respect to their physiological
      properties: a total of 11 different phenotypes could be distinguished. Genomic
      fingerprinting by enterobacterial repetitive intergenic consensus (ERIC)
      polymerase chain reaction (PCR) revealed an even higher diversity of 22 different
      genotypes. A culture-independent analysis by PCR and denaturing-gradient gel
      electrophoresis (DGGE) revealed that the partial 16S rDNA sequence of the
      isolated D. apsheronum strains constituted a significant fraction of the
      Desulfovibrionaceae. The high subspecies diversity suggests that this abundant
      aggregate-forming species may have evolved adaptations to different ecological
      niches in the oxic sediment layers.

PMID- 11234931
TI  - Autotrophy of green non-sulphur bacteria in hot spring microbial mats: biological
      explanations for isotopically heavy organic carbon in the geological record.
AB  - Inferences about the evidence of life recorded in organic compounds within the
      Earth's ancient rocks have depended on 13C contents low enough to be
      characteristic of biological debris produced by the well-known CO2 fixation
      pathway, the Calvin cycle. 'Atypically' high values have been attributed to
      isotopic alteration of sedimentary organic carbon by thermal metamorphism. We
      examined the possibility that organic carbon characterized by a relatively high
      13C content could have arisen biologically from recently discovered autotrophic
      pathways. We focused on the green non-sulphur bacterium Chloroflexus aurantiacus
      that uses the 3-hydroxypropionate pathway for inorganic carbon fixation and is
      geologically significant as it forms modern mat communities analogous to
      stromatolites. Organic matter in mats constructed by Chloroflexus spp. alone had
      relatively high 13C contents (-14.9%) and lipids diagnostic of Chloroflexus that
      were also isotopically heavy (-8.9% to -18.5%). Organic matter in mats
      constructed by Chloroflexus in conjunction with cyanobacteria had a more typical
      Calvin cycle signature (-23.5%). However, lipids diagnostic of Chloroflexus were
      isotopically enriched (-15.1% to -24.1%) relative to lipids typical of
      cyanobacteria (-33.9% to -36.3%). This suggests that, in mats formed by both
      cyanobacteria and Chloroflexus, autotrophy must have a greater effect on
      Chloroflexus carbon metabolism than the photoheterotrophic consumption of
      cyanobacterial photosynthate. Chloroflexus cell components were also selectively
      preserved. Hence, Chloroflexus autotrophy and selective preservation of its
      products constitute one purely biological mechanism by which isotopically heavy
      organic carbon could have been introduced into important Precambrian geological
      features.

PMID- 11234932
TI  - Impact of oxygen on metabolic fluxes and in situ rates of reductive acetogenesis
      in the hindgut of the wood-feeding termite Reticulitermes flavipes.
AB  - The symbiotic digestion of lignocellulose in the hindgut of the wood-feeding
      termite Reticulitermes flavipes is characterized by two major metabolic pathways:
      (i) the oxidation of polysaccharides to acetate by anaerobic hydrogen-producing
      protozoa; and (ii) the reduction of CO2 by hydrogenotrophic acetogenic bacteria.
      Both reactions together would render the hindgut largely homoacetogenic. However,
      the results of this study show that the situation is more complex. By
      microinjection of radiolabelled metabolites into intact agarose-embedded
      hindguts, we showed that the in situ rates of reductive acetogenesis (3.3 nmol
      termite(-1) h(-1)) represent only 10% of the total carbon flux in the living
      termite, whereas 30% of the carbon flux proceeds via lactate. The rapid turnover
      of the lactate pool (7.2 nmol termite(-1) h(-1)) consolidates the previously
      reported presence of lactic acid bacteria in the R. flavipes hindgut and the low
      lactate concentrations in the hindgut fluid. However, the immediate precursor of
      lactate remains unknown; the low turnover rates of injected glucose (< 0.5 nmol
      termite(-1) h(-1)) indicate that free glucose is not an important intermediate
      under in situ conditions. The influence of the incubation atmosphere on the
      turnover rate and the product pattern of glucose and lactate confirmed that the
      influx of oxygen via the gut epithelium and its reduction in the hindgut
      periphery have a significant impact on carbon and electron flow within the
      hindgut microbial community. The in situ rates of reductive acetogenesis were not
      significantly affected by the presence of oxygen or exogenous H2, which is in
      agreement with a localization of homoacetogens in the anoxic gut lumen rather
      than in the oxic periphery. This adds strong support to the hypothesis that the
      co-existence of methanogens and homoacetogens in this termite is based on the
      spatial arrangement of the different populations of the gut microbiota. A refined
      model of metabolic fluxes in the hindgut of R. flavipes is presented.

PMID- 11234934
TI  - The responses of photosynthesis and oxygen consumption to short-term changes in
      temperature and irradiance in a cyanobacterial mat (Ebro Delta, Spain).
AB  - We have evaluated the effects of short-term changes in incident irradiance and
      temperature on oxygenic photosynthesis and oxygen consumption in a hypersaline
      cyanobacterial mat from the Ebro Delta, Spain, in which Microcoleus
      chthonoplastes was the dominant phototrophic organism. The mat was incubated in
      the laboratory at 15, 20, 25 and 30 degrees C at incident irradiances ranging
      from 0 to 1,000 micromol photons m(-2) s(-1). Oxygen microsensors were used to
      measure steady-state oxygen profiles and the rates of gross photosynthesis, which
      allowed the calculation of areal gross photosynthesis, areal net oxygen
      production, and oxygen consumption in the aphotic layer of the mat. The lowest
      surface irradiance that resulted in detectable rates of gross photosynthesis
      increased with increasing temperature from 50 micromol photons m(-2) s(-1) at 15
      degrees C to 500 micromol photons m(-2) s(-1) at 30 degrees C. These threshold
      irradiances were also apparent from the areal rates of net oxygen production and
      point to the shift of M. chthonoplastes from anoxygenic to oxygenic
      photosynthesis and stimulation of sulphide production and oxidation rates at
      elevated temperatures. The rate of net oxygen production per unit area of mat at
      maximum irradiance, J0, did not change with temperature, whereas, JZphot, the
      flux of oxygen across the lower boundary of the euphotic zone increased linearly
      with temperature. The rate of oxygen consumption per volume of aphotic mat
      increased with temperature. This increase occurred in darkness, but was strongly
      enhanced at high irradiances, probably as a consequence of increased rates of
      photosynthate exudation, stimulating respiratory processes in the mat. The
      compensation irradiance (Ec) marking the change of the mat from a heterotrophic
      to an autotrophic community, increased exponentially in this range of
      temperatures.

PMID- 11234933
TI  - Developmental pathway for biofilm formation in curli-producing Escherichia coli
      strains: role of flagella, curli and colanic acid.
AB  - This work was performed to establish a model describing bacterial surface
      structures involved in biofilm development, in curli-overproducing Escherichia
      coli K-12 strains, at 30 degrees C, and in minimal growth medium. Using a genetic
      approach, in association with observations of sessile communities by light and
      electron microscopic techniques, the role of protein surface structures, such as
      flagella and curli, and saccharidic surface components, such as the E. coli
      exopolysaccharide, colanic acid, was determined. We show that, in the context of
      adherent ompR234 strains, (i) flagellar motility is not required for initial
      adhesion and biofilm development; (ii) both primary adhesion to inert surfaces
      and development of multilayered cell clusters require curli synthesis; (iii)
      curli display direct interactions with the substratum and form interbacterial
      bundles, allowing a cohesive and stable association of cells; and (iv) colanic
      acid does not appear critical for bacterial adhesion and further biofilm
      development but contributes to the biofilm architecture and allows for the
      formation of voluminous biofilms.

PMID- 11234935
TI  - Web alert. Bioactive natural products from soil microorganisms.

PMID- 11234936
TI  - Anterior cruciate ligament injuries in the skeletally immature patient.
AB  - Injuries to the anterior cruciate ligament in children and youth pose a complex
      clinical challenge. The literature does not provide the clinician with a well
      defined natural history or pathoanatomy, nor does it show agreement as to the
      outcomes of various treatment choices. Decision making is made difficult by the
      patients' skeletal and emotional immaturity and by associated intra-articular
      fracture, physeal fracture, and combination injuries. In an effort to place the
      problem of ACL injury in children and youth into some perspective and to present
      an algorithm for management, this article reviews issues in its diagnosis,
      classification, anatomy, mechanism of injury, and management.

PMID- 11234937
TI  - An analysis of burst fractures of the spine in adolescents.
AB  - Burst fractures are less common in children than in adults because of the greater
      mobility and elasticity of the pediatric spine. Because of these spine
      characteristics, these fractures may behave differently in childhood than in
      adulthood. To try to address these differences, we reviewed our experience with
      11 children (5 boys, 6 girls) treated for burst fractures. Average age at time of
      injury was 14.4 years. Follow-up averaged 9 years. All fractures were categorized
      using the Denis classification system for burst fractures. Three children had
      associated spinal cord injury. Five children were treated with nonoperative
      bedrest and casting; the other 6 children, who had the most severe burst
      fractures, were treated with posterior spinal fusion and instrumentation.
      Satisfactory functional results were found in 90% of the children at follow-up.
      Radiological evaluation at initial and follow-up examination showed that children
      treated operatively improved or maintained their fracture kyphosis (range, 12
      degrees - 19 degrees). Anterior vertebral compression improved an average of 15%
      (range, 24%-39%). In the children treated nonoperatively, kyphosis progressed an
      average of 9 degrees (range, 15 degrees - 24 degrees), and anterior vertebral
      compression increased a further 8% (range, 36%-44%). Our results showed that (a)
      the children who sustained burst fractures tended to develop mild progressive
      angular deformity at the site of the fracture, (b) operative stabilization
      prevented further kyphotic deformity as well as decreased the length of
      hospitalization without contributing to further cord compromise, and (c)
      nonoperative treatment of burst fracture was a viable option in neurologically
      intact children, but progressive angular deformity occurred during the first year
      after the fracture.

PMID- 11234938
TI  - Peripheral neuropathy in the hands of diabetic patients with lower extremity
      amputations.
AB  - One hundred unilateral ambulatory lower extremity amputees underwent sensibility
      testing of their remaining foot and right hands to determine if the magnitude of
      peripheral neuropathy present in the feet of patients with diabetes was of
      greater magnitude than that in their hands. Testing was performed with a series
      of Semmes-Weinstein monofilaments. Ninety-one of the subjects were male, and 9
      were female. Sixty-five were diabetic, 40 required insulin. The magnitude of
      peripheral neuropathy was compared between the hands and feet of patients with
      and without diabetes, and between insulin-dependent and non-insulin-dependent
      diabetics. There was a slight trend to a more severe degree of insensitivity in
      the feet as compared with the hands in each of the individual groups. There was
      no statistically significant difference when comparing hand and foot sensibility
      in any of the comparison groupings. The quantitative amount of peripheral
      neuropathy appears to affect the hands and feet of diabetics in a similar
      "stocking-glove" fashion. The results of this screening gives further support to
      the concept of prophylactic foot care programs in diabetics with peripheral
      neuropathy to decrease the risk for the development of foot ulcers, which are
      often the precursor of eventual lower extremity amputation.

PMID- 11234939
TI  - Treatment of ulnar impaction syndrome with the wafer procedure.
AB  - Our objective was to evaluate the efficacy of wafer resection of the distal ulna
      (the wafer procedure) as treatment for ulnar impaction syndrome. Between 1995 and
      1997, 26 patients were surgically treated for refractory wrist pain secondary to
      ulnar impaction syndrome. The diagnosis was based on physical examination,
      radiologic imaging, and wrist arthroscopy, and confirmatory pathoanatomy was
      identified at the time of surgery in all cases. The study population consisted of
      18 women and 8 men, and patient age averaged 42 years. Follow-up averaged 27
      months (range, 17-41 months). Twenty-three patients were completely satisfied
      with pain relief and the functional status of their wrists at final follow-up.
      Range of motion returned to baseline in the majority of cases, usually by 3
      months, and grip strength increased an average of 11 kg (P < or = .005). The
      wafer procedure is an effective treatment alternative to ulnar-shortening
      osteotomy for ulnar impaction syndrome and avoids the risk of nonunion and
      hardware-related complications.

PMID- 11234940
TI  - Fibrous dysplasia of both alae of the sacrum.
AB  - A case of monostotic fibrous dysplasia involving both alae of the sacrum is
      reported. Only 2 cases of monostotic sacral involvement were published
      previously. The lesion was detected in a 42-year-old man suffering from
      lumbosacral pain after minimal trauma. Radiographic studies revealed cystic
      images on both alae of the sacrum, with internal condensations and some liquid
      contents. A trephine biopsy did not produce enough diagnostic data, and a
      posterior surgical approach was elected. Curettage and refilling with allograft
      were performed. The pathologic anatomy study diagnosed a fibrous dysplasia. Two
      years after surgery, the patient was asymptomatic.

PMID- 11234941
TI  - Irreducible knee dislocations secondary to interposed menisci.
AB  - Dislocations of the knee are accompanied by a highly variable pattern of osseous
      and soft tissue injury. While much attention has been directed toward the various
      combinations of ligament involvement observed in these injuries, the patterns of
      associated meniscal injury are described less frequently. We report two cases of
      patients in whom displaced medial meniscal tears prevented closed reduction
      following knee dislocation. Displaced bucket-handle meniscal tears necessitated
      open reduction in these patients and should be considered when evaluating
      patients with knee dislocations.

PMID- 11234942
TI  - Migration of a K-wire from the distal radius to the heart.
AB  - K-wires and Steinmann pins are used to provide internal fixation for fractures or
      osteotomies. In some instances, removal of the implant is planned and the implant
      is left long to facilitate its removal. In other instances, implant removal is
      not planned and the implant is cut off at the level of the bone. Migration of
      these implants to solid organs or body cavities has been reported. Extravascular
      migration may occur along tissue planes assisted by muscle motion. Large vessel
      penetration can occur and has been reported with subsequent migration of the
      implant to the heart. This case report documents the loosening of a K-wire used
      in the distal radius to supplement the fixation of a complex intra-articular
      fracture, migration of the implant along tissue planes, penetration into a
      peripheral vein, and continued migration of the implant to the heart. There are
      multiple reports documenting wandering bullets, venous catheter tips, and
      invasive monitoring devices in the extremities. This is only the second case
      report that the authors are aware of that confirms migration of an implant from
      the distal extremity to the heart.

PMID- 11234943
TI  - Myositis ossificans after a supracondylar fracture of the humerus in a child.
AB  - Myositis Ossificans After a Supracondylar Fracture of the Humerus in a Child. In
      addition to the better known complications of supracondylar humerus fractures,
      myositis ossificans is often listed as a less common complication. This
      complication is extremely rare in children and historically has been attributed
      to high-energy trauma, manipulation, surgical intervention, aggressive passive
      range-of-motion exercises, or associated head injury. We present a case report of
      a 3-year-old girl who developed myositis ossificans after a low-energy
      supracondylar fracture of the humerus despite having been treated without
      manipulation, surgery, or physical therapy. This report illustrates that
      supracondylar humerus fractures can be complicated by myositis ossificans despite
      the best attempts at prevention.

PMID- 11234944
TI  - Diagnostic capabilities of shoulder ultrasonography in the detection of complete
      and partial rotator cuff tears.
AB  - Our study assessed the accuracy of shoulder ultrasonography in detecting complete
      and partial rotator cuff tears. We performed a prospective study in 24 patients
      scheduled for shoulder arthroscopy for impingement, partial-thickness or full
      thickness (complete) rotator cuff tears, adhesive capsulitis, or arthritis.
      Before surgery, all patients underwent diagnostic shoulder ultrasonography
      followed by a shoulder arthroscopy with examination of the rotator cuff. The
      arthroscopic findings of rotator cuff integrity were compared with the diagnoses
      made from ultrasonography. The ultrasonographer was not blinded to the history
      and examination findings, and the surgeon was not blinded to the results of the
      ultrasonography. Ultrasound had sensitivity and specificity rates of 80% and
      100%, respectively (positive and negative predictive rates of 100% and 88%), in
      the diagnosis of full-thickness rotator cuff tears and sensitivity and
      specificity rates of 71% and 100%, respectively (positive and negative predictive
      values of 100% and 88%), for partial-thickness tears. Although the potential for
      bias exists in this study, the results suggest that diagnostic ultrasound is
      effective in the diagnosis of rotator cuff tears.

PMID- 11234945
TI  - Synovial osteochondromatosis.

PMID- 11234946
TI  - Visiting professors.

PMID- 11234947
TI  - Microbial formation, biotechnological production and applications of 1,2
      propanediol.
AB  - This short review covers metabolic pathways, genetics and metabolic engineering
      of 1,2-propanediol formation in microbes. 1,2-Propanediol production by bacteria
      and yeasts has been known for many years and two general pathways are recognized.
      One involves the metabolism of deoxyhexoses, where lactaldehyde is formed during
      the glycolytic reactions and is then reduced to 1,2-propanediol. The second
      pathway derives from the formation of methylglyoxal from
      dihydroxyacetonephosphate and its subsequent reduction to 1,2-propanediol. The
      enzymes involved in the reduction of methylglyoxal can generate isomers of
      lactaldehyde or acetol, which can be further reduced by specific reductases,
      giving chiral 1,2-propanediol as the product. The stereospecificity of the
      enzymes catalyzing the two reduction steps is important in deriving a complete
      pathway. Through genetic engineering, appropriate combinations of enzymes have
      been brought together in Escherichia coli and yeast to generate 1,2-propanediol
      from glucose. The optimization of these strains may yield microbial processes for
      the production of this widely used chemical.

PMID- 11234948
TI  - Biological production of 2,3-butanediol.
AB  - 2,3-Butanediol (2,3-BDL), which is very important for a variety of chemical
      feedstocks and liquid fuels, can be derived from the bioconversion of natural
      resources. One of its well known applications is the formation of methyl ethyl
      ketone, by dehydration, which can be used as a liquid fuel additive. This article
      briefly reviews the basic properties of 2,3-BDL and the metabolic pathway for the
      microbial formation of 2,3-BDL. Both the biological production of 2,3-BDL and the
      variety of strains being used are introduced. Genetically improved strains for
      BDL production which follow either the original mechanisms or new mechanisms are
      also described. Studies on fermentation conditions are briefly reviewed. On-line
      analysis, modeling, and control of BDL fermentation are discussed. In addition,
      downstream recovery of 2,3-BDL and the integrated process (being important issues
      of BDL production) are also introduced.

PMID- 11234949
TI  - Biodegradation of sulfanilic acid by Pseudomonas paucimobilis.
AB  - An aerobic bacterium, isolated from a contaminated site, was able to degrade
      sulfanilic acid (4-aminobenzenesulfonic acid) and was identified as Pseudomonas
      paucimobilis. The isolate could grow on sulfanilic acid (SA) as its sole carbon
      and nitrogen source and metabolized the target compound to biomass. The
      bioconversion capacity depended on the sulfanilic acid concentration; greater
      than 98% elimination of the hazardous compound was achieved at low (10 mM)
      sulfanilic acid concentration, and the yield was greater than 70% at 50 mM
      concentration of the contaminant. The maximum conversion rate was 1.5 mmol
      sulfanilic acid/h per mg wet cells at 30 degrees C. Ca-alginate-phytagel proved a
      good matrix for immobilization of P. paucimobilis, with essentially unaltered
      biodegradation activity. Removal of sulfanilic acid from contaminated industrial
      waste water was demonstrated. SDS-PAGE analysis of the crude extract revealed
      novel proteins appearing upon induction with sulfanilic acid and related
      compounds, which indicated alternative degradation mechanisms involving various
      inducible enzymes.

PMID- 11234950
TI  - Genetic reidentification of the pectinolytic yeast strain SCPP as Saccharomyces
      bayanus var. uvarum.
AB  - Using genetic hybridization analysis, pulsed-field gel electrophoresis of
      chromosomal DNA and PCR/RFLP analysis of the MET2 gene, we reidentified 11
      Champagne yeast strains. Two of them, SCPP and SC4, were found to belong to
      Saccharomyces bayanus var. uvarum and the remaining strains to S. cerevisiae.
      Strain

PMID- 11234951
TI  - Development and utilisation of a medium to isolate phenanthrene-degrading
      Pseudomonas spp.
AB  - In this study, we isolated phenanthrene degraders belonging to Pseudomonas spp.
      by combining the selective force of two previously described media. The two
      compounds, sodium lauryl sarcosine and trimethoprim, from the Gould S1 medium,
      were added to minimal agar plates sprayed with phenanthrene. Pseudomonas spp.
      that could produce clearing zones were isolated in one step from the rhizosphere
      without first selecting for Pseudomonas spp. and subsequently screening for
      degraders or vice versa. Enumeration and isolation of Pseudomonas spp. attached
      to the rhizosphere showed clear differences between two types of soil.
      Rhizosphere-attached phenanthrene degraders (from Pseudomonas spp.) were isolated
      from a former coal gasification site, but were absent in an agricultural soil
      subjected to organic farming. We isolated 23 phenanthrene degraders producing
      clearing zones from the rhizosphere of barley roots. All of these 23 isolates (of
      which 16 were fluorescent in UV light) proved to be members of the Pseudomonas
      RNA homology group I, on the basis of results of the analytical profile index
      (API) test system and classic taxonomic tests.

PMID- 11234952
TI  - Biodegradation of ethyl t-butyl ether (ETBE), methyl t-butyl ether (MTBE) and t
      amyl methyl ether (TAME) by Gordonia terrae.
AB  - Gordonia terrae strain IFP 2001 was selected from activated sludge for its
      capacity to grow on ethyl t-butyl ether (ETBE) as sole carbon and energy source.
      ETBE was stoichiometrically degraded to t-butyl alcohol (TBA) and the activity
      was inducible. A constitutive strain, G. terrae IFP 2007, derived from strain IFP
      2001, was also selected. Methyl t-butyl ether (MTBE) and t-amyl methyl ether
      (TAME) were not used as carbon and energy sources by the two strains, but
      cometabolic degradation of MTBE and TAME was demonstrated, to TBA and t-amyl
      alcohol (TAA) respectively, in the presence of a carbon source such as ethanol.
      No two-carbon compound was detected during growth on ETBE, but formate was
      produced during cometabolic degradation of MTBE or TAME. A monooxygenase was
      involved in the degradation of ethers, because no degradation of ETBE was
      observed under anaerobic conditions and the presence of a cytochrome P-450 was
      demonstrated in G. terrae IFP 2001 after induction by cultivation on ETBE.

PMID- 11234954
TI  - Pro- and prebiotics--the tasty guardian angels?
AB  - It is generally accepted that the bacterial community resident in the human
      intestinal tract has a major impact on gastrointestinal function and thereby on
      human health and well-being. Considerable efforts have been made to influence the
      intestinal microbiota by dietary means in such a way that the health of the host
      is beneficially affected. Pro- and prebiotics are food products that are
      specially designed for this purpose. Parallel to the increase in the acceptance
      of such products by the consumer, the scientific interest in the mechanisms
      underlying their presumed effects, such as pathogen inhibition, immune modulation
      or anti-carcinogenicity, has grown continuously in recent years. Some of these
      effects have been established by several independent studies, but others are
      still controversial. This review relates the health claims made for the pro- and
      prebiotic food products to the facts established by in vivo and in vitro studies.
      The assessment of pro- and prebiotic effects on the microbial gut ecosystem is
      highly improved and facilitated by the application of molecular methods.
      Biotechnological aspects of the production of pro- and prebiotics are discussed.

PMID- 11234953
TI  - BTEX catabolism interactions in a toluene-acclimatized biofilter.
AB  - BTEX substrate interactions for a toluene-acclimatized biofilter consortium were
      investigated. Benzene, ethylbenzene, o-xylene, m-xylene and p-xylene removal
      efficiencies were determined at a loading rate of 18.07 g m(-3) h(-1) and
      retention times of 0.5-3.0 min. This was also repeated for toluene in a 1:1 (m/m)
      ratio mixture (toluene: benzene, ethylbenzene, or xylene ) with each of the other
      compounds individually to obtain a final total loading of 18.07 g m(-3) h(-1).
      The results obtained were modelled using Michaelis-Menten kinetics and an
      explicit finite difference scheme to generate vmax and Km parameters. The Vmax/Km
      ratio (a measure of the catalytic efficiency, or biodegradation capacity, of the
      reactor) was used to quantify substrate interactions occurring within the
      biofilter reactor without the need for free-cell suspended and monoculture
      experimentation. Toluene was found to enhance the catalytic efficiency of the
      reactor for p-xylene, while catabolism of all the other compounds was inhibited
      competitively by the presence of toluene. The toluene-acclimatized biofilter was
      also able to degrade all of the other BTEX compounds, even in the absence of
      toluene. The catalytic efficiency of the reactor for compounds other than toluene
      was in the order: ethylbenzene > benzene > o-xylene > m-xylene>p-xylene. The
      catalytic efficiency for toluene was reduced by the presence of all other tested
      BTEX compounds, with the greatest inhibitory effect being caused by the presence
      of benzene, while o-xylene and p-xylene caused the least inhibitory effect. This
      work illustrated that substrate interactions can be determined directly from
      biofilter reactor results without the need for free-cell and monoculture
      experimentation.

PMID- 11234955
TI  - Anaerobic sequencing batch reactors for wastewater treatment: a developing
      technology.
AB  - This paper describes and discusses the main problems related to anaerobic batch
      and fed-batch processes for wastewater treatment. A critical analysis of the
      literature evaluated the industrial application viability and proposed
      alternatives to improve operation and control of this system. Two approaches were
      presented in order to make this anaerobic discontinuous process feasible for
      industrial application: (1) optimization of the operating procedures in reactors
      containing self-immobilized sludge as granules, and (2) design of bioreactors
      with inert support media for biomass immobilization.

PMID- 11234956
TI  - Chemostat study of xylitol production by Candida guilliermondii.
AB  - The mechanism of production of xylitol from xylose by Candida guilliermondii was
      studied using chemostat cultures and enzymatic assays. The maximum dilution rate
      in aerobic conditions was 0.34 1/h. No xylitol was produced. Under oxygen-limited
      conditions xylose uptake was impaired and glycerol accumulated but no xylitol was
      detected. Under transient oxygen limitation, caused by a gradual decrease in the
      agitation rate, onset of xylitol, acetate and residual xylose accumulation
      occurred simultaneously when qo2 dropped below 25 mmol/C-mmol cell dry weight
      (CDW) per hour. Ethanol and glycerol started to accumulate when qo2 dropped below
      20 mmol/C-mmol CDW per hour. The highest in vitro enzyme activities were found at
      the lowest dilution rate studied (0.091/h) under aerobic conditions. The amount
      of active enzymes or cofactor availability did not limit the rate of xylose
      consumption. Our results confirm that a surplus of NADH during transient oxygen
      limitation inhibited the activity of xylitol dehydrogenase which resulted in
      xylitol accumulation. Phosphoglucoisomerase (E.C. 5.3.1.9.) and glucose-6
      phosphate dehydrogenase (E.C. 1.1.1.49) activities suggest re-shuttling of the
      metabolites into the pentose phosphate pathway.

PMID- 11234957
TI  - Anaerobic desulfurization of ground rubber with the thermophilic archaeon
      Pyrococcus furiosus--a new method for rubber recycling.
AB  - The anaerobic sulfur-reducing archaeon Pyrococcus furiosus was investigated
      regarding its capacity to desulfurize rubber material. The microorganism's
      sensitivity towards common rubber elastomers and additives was tested and several
      were shown to be toxic to P. furiosus. The microorganism was shown to utilize
      sulfur in vulcanized natural rubber and an increase in cell density was obtained
      when cultivated in the presence of spent tire rubber. Ethanol-leached cryo-ground
      tire rubber treated with P. furiosus for 10 days was vulcanized together with
      virgin rubber material (15% w/w) and the mechanical properties of the resulting
      material were determined. The increase in the stress at break value and the
      decrease in swell ratio and stress relaxation rate obtained for material
      containing microbially treated rubber (compared to untreated material) show the
      positive effects of microbial desulfurization on rubber.

PMID- 11234958
TI  - Idle time in the washing and iron concentration in leachate removed: two basic
      parameters in the desulphurization of coal in a packed column.
AB  - Column biodesulphurization of coal is at the experimental stage and is influenced
      by many variables including temperature, pH, particle size, concentration of iron
      in solution, among others. Idle time in the washing process and the concentration
      of dissolved iron in the purged leachate are two variables with a definite effect
      on the yield of the desulphurization system. In the laboratory, several trials
      were run with columns packed with coal for different idle times: 1, 2, 3, 5, 6
      and 7 days, and for different concentrations of iron in the purged leachate: 500
      to 4,000 mg/l. The optimal values for the two variables; that is, those allowing
      for the highest desulphurization yields, were idle times of 3 and 5 days, which
      give an elimination of 56% and 49% of pyritic sulphur, respectively, and 3,000
      mg/l of iron concentration in the purged leachate, giving a decrease in pyritic
      sulphur in coal of 57%.

PMID- 11234959
TI  - Application of high performance anion exchange chromatography to study invertase
      catalysed hydrolysis of sucrose and formation of intermediate fructan products.
AB  - Baker's yeast invertase was found to catalyse transfructosylation reactions in
      aqueous and anhydrous organic media with sucrose as a substrate, leading to the
      formation of five intermediate fructans in addition to the release of D-glucose
      (D-Glc)and D-fructose (D-Fru). All the reaction products were separated and
      quantitatively estimated using high performance anion exchange-pulsed
      amperometric detection equipment. The unknown products were subsequently
      identified by linkage analysis as beta-D-Fru-(2 --> 1)-beta-D-Fru-(2 --> 1)-
      alpha-D-glucopyranoside (1-kestose), beta-D-Fru- (2 --> 6)-alpha-D
      glucopyranoside (6-beta-fructofuranosylglucose), beta-D-Fru-(2 -->1) -beta-D
      fructofuranoside (inulobiose), beta-D-Fru-(2 --> 6)-beta-D-Fru-(2 --> 1)-alpha-D
      glucopyranoside (6-kestose) and beta-D-Fru-(2 --> 6)-alpha-D-Glc-(1 --> 2)-beta-D
      fructofuranoside (neokestose); and this last was eluted together with a
      disaccharide. The time-course of sucrose hydrolysis via fructan production in 2
      ml of a 50 mM sodium acetate buffer (pH 4.5) containing 0.2 M sucrose and 25 U of
      invertase was different from that in 2 ml of anhydrous toluene with 1.46 M
      sucrose and 1,000 U of invertase as a suspended powder. Under the latter
      experimental conditions, invertase was found to exhibit cyclic behaviour, where
      sucrose was degraded and subsequently synthesised. This observation has not yet
      been reported, as far as we know.

PMID- 11234960
TI  - Molecular cloning and characterization of a multidomain endoglucanase from
      Paenibacillus sp BP-23: evaluation of its performance in pulp refining.
AB  - The gene celB encoding an endoglucanase from Paenibacillus sp. BP-23 was cloned
      and expressed in Escherichia coli. The nucleotide sequence of a 4161 bp DNA
      fragment containing the celB gene was determined, revealing an open reading frame
      of 2991 nucleotides that encodes a protein of 106,927 Da. Comparison of the
      deduced amino acid sequence of endoglucanase B with known beta-glycanase
      sequences showed that the encoded enzyme is a modular protein and exhibits high
      homology to enzymes belonging to family 9 cellulases. The celB gene product
      synthesized in E. coli showed high activity on carboxymethyl cellulose and
      lichenan while low activity was found on Avicel. Activity was enhanced in the
      presence of 10 mM Ca2+ and showed its maximum at 53 degrees C and pH 5.5. The
      effect of the cloned enzyme in modifying the physical properties of pulp and
      paper from Eucalyptus was tested (CelB treatment). An increase in mechanical
      strength of paper and a decrease in pulp dewatering properties were found,
      indicating that CelB treatment can be considered as a biorefining. Treatment with
      CelB gave rise to an improvement in paper strength similar to that obtained with
      1,000 revolutions increase in mechanical refining. Comparison with the
      performances of recently developed endoglucanase A from the same strain and with
      a commercial cellulase showed that CelB produced the highest refining effect.

PMID- 11234961
TI  - Construction of protein overproducer strains in Bacillus subtilis by an
      integrative approach.
AB  - We evaluated the effect of several genetic factors reported as having a role in
      the induction of the expression of significant levels of recombinant protein in
      Bacillus subtilis. We utilized the beta-galactosidase reporter protein from
      Escherichia coli as our model for measuring the overproduction of heterologous
      proteins in B. subtilis. The lacZ gene was expressed in B. subtilis using the
      regulatory region of the subtilisin gene aprE. In this study, we considered
      factors known to modulate the transcription and translation initiation rates and
      genetic and mRNA stability. We also consider the effects of different genetic
      backgrounds, such as degU32 and hpr2, that until now have been studied
      independently. By changing the native -35 promoter box to the consensus TTGACA
      sequence of the aprE promoter, a significant 100-fold increase in the beta
      galactosidase activity was obtained. On the other hand, changes such as the GTG
      to ATG start codon, the construction of a consensus AAGGAGG ribosome binding
      site, and the addition of the cryIIIA transcription terminator at the 3' end of
      the lacZ gene, produced only marginal effects on the final beta-galactosidase
      activity.

PMID- 11234962
TI  - Xylitol production by recombinant Saccharomyces cerevisiae expressing the Pichia
      stipitis and Candida shehatae XYL1 genes.
AB  - The xylose reductase gene (XYL1) was isolated from Pichia stipitis and Candida
      shehatae, cloned into YEp-based vectors under the control of ADH2 and PGK1
      promoter/terminator cassettes and introduced into Saccharomyces cerevisiae Y294
      by electroporation. Shake-flask fermentations were carried out with 5% xylose and
      1% galactose, glucose or maltose as co-substrates. Xylose uptake was similar in
      both the recombinant strains when different co-substrates were used and slowed
      once the co-substrate was depleted. The recombinant strains converted xylose to
      xylitol with yields approaching the theoretical maxima. Xylitol production was
      most rapid when the co-substrate was still present. Approximately 50% of the
      xylose was not metabolized due to the depletion of the co-substrate.

PMID- 11234963
TI  - alpha-Amylase production in high cell density submerged cultivation of
      Aspergillus oryzae and A. nidulans.
AB  - The effect of biomass concentration on the formation of Aspergillus oryzae alpha
      amylase during submerged cultivation with A. oryzae and recombinant A. nidulans
      strains has been investigated. It was found that the specific rate of alpha
      amylase formation in chemostats decreased significantly with increasing biomass
      concentration in the range of approx. 2-12 g dry weight kg(-1). When using a
      recombinant A. nidulans strain in which the gene responsible for carbon
      catabolite repression of the A. oryzae alpha-amylase gene (creA) was deleted, no
      significant decrease in the specific rate of alpha-amylase formation was
      observed. On the basis of the experimental results, it is suggested that the low
      value of the specific alpha-amylase productivity observed at high biomass
      concentration is caused by slow mixing of the concentrated feed solution in the
      viscous fermentation medium.

PMID- 11234964
TI  - Carrier-mediated transport of riboflavin in Ashbya gossypii.
AB  - The filamentous hemiascomycete Ashbya gossypii is used for industrial riboflavin
      production. We examined riboflavin uptake and excretion at the plasma membrane
      using riboflavin auxotrophic and overproducing mutants. The riboflavin uptake
      system had low activity [Vmax = 20 +/- 4 nmol min(-1) g(-1) mycelial dry weight
      (dw)] and high affinity (KM = 40 +/- 12 microM). Inhibitor studies with the
      analogs FMN and FAD revealed high specificity of the uptake system. Excretion of
      riboflavin was not the consequence of non-specific permeability of the plasma
      membrane. Excretion rates in the mid-production phase were determined to be 2.5
      nmol min(-1) g(-1) dw for wild-type cells and 66.7 nmol min(-1) g(-1) dw for an
      overproducing mutant, respectively. Inhibition of the reverse reaction,
      riboflavin uptake, led to an increase in apparent riboflavin efflux in the early
      production phase, indicating the presence of a separate excretion carrier.
      Riboflavin accumulation in A. gossypii vacuoles leading to product retention was
      found to be a secondary transport process. To address the question of whether a
      flux from the vacuoles back into the cytoplasm is present, we characterized
      efflux in hyphae in which the plasma membrane was permeabilized with digitonin.
      Efflux kinetics across the vacuolar membrane were unaffected by the lack of
      vacuolar H+ATPase activity and ATP, suggesting a passive mechanism. Based on the
      characterization of riboflavin transport processes in this study, the design of
      new production strains with improved riboflavin excretion may be possible.

PMID- 11234965
TI  - Nitrate reduction by Citrobacter diversus under aerobic environment.
AB  - A new aerobic denitrifier, Citrobacter diversus, was isolated from both
      nitrification and denitrification sludge. To monitor the variation in the
      concentration of nitrogen oxides, aerobic denitrification by C. diversus was
      carried out in a batch reactor. When the nitrate concentration was greater than
      180 mg N l(-1), the nitrate reduction rate became stable. The effect of the C/N
      ratio on the denitrification activity was also investigated. The results showed
      that the optimum denitrification activity was obtained when the C/N ratio was 4
      5. The range of the C/N ratio was higher than that for traditional anoxic
      denitrification. The effect of the dissolved oxygen concentration was further
      studied; and it was found that the range of dissolved oxygen concentrations, both
      for specific growth rates and for specific denitrification rates, was 2-6 mg(-1).
      From these results, it can be concluded that both the concentration of dissolved
      oxygen and the C/N ratio are key factors in the aerobic denitrification by C.
      diversus.

PMID- 11234967
TI  - Seroprevalence of Border Disease in Danish sheep and goat herds.
AB  - A study was conducted in 1994-96 with the aim of assessing the serological
      prevalence of Border Disease (BD) among sheep and goats in Denmark and to
      investigate possible relations to herd factors. From each of 1000 herds, 2 blood
      samples were obtained from animals older than 1 year. The examination for
      antibodies was performed using a blocking ELISA detecting antibodies to
      pestivirus. Data from 815 herds were analysed statistically by the maximum
      likelihood method in a multinomial model. The estimated herd prevalence was 0.083
      and the estimated individual prevalence within the positive herds was 0.50. There
      was no difference between the prevalence in sheep and goat herds. Records for
      well over half of the herds could be combined with data from the Danish Central
      Husbandry Register. No association between occurrence of BD and herd size was
      found. Cattle were registered as contemporarily present on 135 out of 521 herds
      which was shown to be strongly associated to BD. The estimated herd prevalences
      of BD among farms with and without contemporary cattle were 0.24 and 0.042,
      respectively.

PMID- 11234966
TI  - Enzymatic reduction of chromate: comparative studies using sulfate-reducing
      bacteria. Key role of polyheme cytochromes c and hydrogenases.
AB  - Various sulfate-reducing bacteria of the genera Desulfovibrio and
      Desulfomicrobium were tested and compared for enzymatic reduction of chromate.
      Our study demonstrated that the ability to reduce chromate is widespread among
      sulfate-reducing bacteria. Among them, Desulfomicrobium norvegicum reduced Cr(VI)
      with the highest reaction rate. This strain grew in the presence of up to 500
      microM chromate, but Cr(VI) reduction in the absence of sulfate was not
      associated with growth. The presence of chromate induced morphological changes
      and leakage of periplasmic proteins into the medium. The ability of isolated
      polyheme cytochromes c from sulfate- and sulfur-reducing bacteria to reduce
      chromate was also analyzed. Tetraheme cytochrome c3(Mr. 13,000) from
      Desulfomicrobium norvegicum showed twice as much activity as either tetraheme
      cytochrome c3 from Desulfovibrio vulgaris strain Hildenborough or triheme
      cytochrome c7 from Desulfuromonas acetoxidans. Results with cytochromes c3 and
      other c-type cytochromes altered by site-directed mutagenesis indicated that
      negative redox potential hemes are crucial for metal reductase activity. The
      present study also demonstrated that the (Fe) hydrogenase from sulfate-reducing
      bacteria could reduce chromate.

PMID- 11234968
TI  - Microsatellite marker C04107 as a diagnostic marker for copper toxicosis in the
      Danish population of Bedlington terriers.
AB  - The linkage phase of marker C04107 was evaluated before implementation of the
      marker in a diagnostic test. Blood samples from 68 dogs were collected and
      genotyped by PCR. Two alleles were detected with sizes of 160 bp and 164 bp and
      allele frequencies of 0.45 and 0.55 respectively. Genotyping revealed that 35
      dogs were heterozygous (51.5%), 22 dogs were homozygous for the normal allele
      (32.3%) and 11 dogs were homozygous for the disease allele (16.2%). Liver
      biopsies were taken from 14 selected dogs and the copper content was evaluated
      histologically. Biopsies from 8 dogs homozygous for the disease allele showed
      many copper granules along with single cell necrosis, haemosiderosis and cellular
      infiltration. In liver biopsies from 6 dogs genotyped to be heterozygous or
      homozygous for the normal allele, copper granules were absent or moderate in
      number and no lesions were present. The survey demonstrates that the linkage
      phase of marker C04107 in the Danish population of Bedlington terriers is similar
      to the linkage phase detected in other countries. Thus, the marker can be used in
      a diagnostic test for copper toxicosis in Denmark.

PMID- 11234969
TI  - The effect of birdsfoot trefoil (Lotus corniculatus) and white clover (Trifolium
      repens) in mixed pasture swards on incoming and established nematode infections
      in young lambs.
AB  - Lotus corniculatus L., a leguminous plant containing condensed tannins, is now
      being evaluated in Sweden as a component of mixed pastures. This is because of
      its high nutritive value, palatability, modest requirement for water, calcium and
      phosphorous and particularly because it has the ability to survive harsh weather
      conditions that typify northern Scandinavia. This trial was undertaken to assess
      the possible parasitological benefits of using L. corniculatus when fed as a
      minor component in a mixed pasture sward to young sheep. This was compared with
      similar sheep that were fed pasture with a comparable legume content consisting
      of Trifolium repens L. Separate groups of lambs, maintained in pens and provided
      with fresh pasture cuts containing either L. corniculatus or T. repens each day,
      were trickle-dosed with infective larvae of mixed parasite species. For each
      pasture type, groups of 6 lambs had either established worm burdens only,
      received incoming infections only, or had the combination of both adult and
      incoming infections. Worm burdens were monitored by serial faecal egg counts and
      at the termination of the study, all animals were slaughtered for worm recovery,
      identification and enumeration. The results showed that there were no
      differential effects between L. corniculatus and T. repens on the different
      stages of development for a range of nematode parasite species recovered from
      these lambs. Several reasons may account for this: such as the low level of
      condensed tannins in the L. corniculatus variety tested, the minor proportion of
      this plant in the diet and/or the variety of L. corniculatus used in this trial
      which do not provide any benefits to controlling parasites of sheep.

PMID- 11234970
TI  - Cytokeratins of the stratum medium and stratum internum of the equine hoof wall
      in acute laminitis.
AB  - The cytoskeleton of living keratinocytes consists mainly of cytokeratins that
      have polymerised into intermediate filaments. The aim of this study was to
      describe the expression of cytokeratins in the living epidermal cells of the
      weight-bearing parts of the equine hoof wall during acute spontaneous laminitis.
      A total of 9 hooves from 3 horses subjected to euthanasia within 48 h of the
      first clinical signs of laminitis were sectioned and examined. The cytokeratins
      in the stratum medium and stratum internum of the hoof wall were characterized by
      1- and 2-dimensional gel electrophoresis, and the tissue distribution of the
      cytokeratins was studied by immunohistochemical staining. The biochemical results
      showed the same set of cytokeratins as was seen in 8 normal horses, reported on
      previously, used as controls. The immunohistochemical results indicated a
      difference between normal horses and horses with acute laminitis in the content
      of cytokeratins in the basal cells of the matrix of the stratum medium of the
      hoof wall and in the basal and suprabasal cells in the stratum internum at the
      mid level of the hoof wall. However, no conclusion could be drawn as to whether
      this change in the cytokeratin distribution in laminitis was primary or was
      caused by the initiation of the local tissue-repairing process.

PMID- 11234971
TI  - Plasma erythropoietin in newborn lambs.
AB  - In the present study early postnatal changes in erythropoietin (Epo) level and
      hemoglobin concentration in 8 lambs were examined. Plasma Epo was estimated by a
      monoclonal enzyme-immunoassay (ELISA), developed for human Epo. In all the lambs,
      except one, Epo was low, or undetectable, immediately after birth. Within 6-12 h
      after birth, a marked increase in plasma Epo was found in 4 of the lambs. Within
      3-7 days after birth, Epo was back to low levels. In the lamb with high Epo
      levels at birth, drastic decreases were observed during the next 6 h. There was
      no obvious correlation between the hemoglobin concentrations and the changes in
      plasma Epo.

PMID- 11234973
TI  - The syndrome of inappropriate secretion of antidiuretic hormone and fluid
      restriction in meningitis--how strong is the evidence?
AB  - In patients with meningitis, fluid restriction is recommended to counter the
      syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and to reduce
      cerebral oedema. However, any effects of an increased plasma level of ADH upon
      cerebral oedema would be due not to fluid retention but to hypoosmolality. In a
      literature review of fluid and electrolyte disturbances and the effect of fluid
      therapy in bacterial/tuberculous meningitis, the prevalence of hyponatraemia,
      hypoosmolality and SIADH varied considerably; apparently, non-osmotic stimuli for
      the secretion of ADH, e.g. intracranial hypertension and hypovolaemia, were
      present in most patients. Neither clinical nor experimental studies have
      confirmed that fluid restriction reduces the cerebral oedema in meningitis.
      Furthermore, compared with maintenance therapy, fluid restriction did not improve
      outcome in a randomized controlled study. Thus, we find no evidence to support
      the use of fluid restriction in patients with meningitis. Fluid therapy in acute
      bacterial meningitis should aim at avoiding hypovolaemia and hypoosmolality based
      on the assumptions that (i) ADH is increased by non-osmotic stimuli; (ii)
      elevated ADH is less important for cerebral oedema than severe hypoosmolality,
      which may in itself induce or aggravate oedema; (iii) maintenance fluid therapy
      aiming at isoosmolality will not worsen neurological outcome; and (iv)
      hypovolaemia is difficult to detect, and detrimental for cerebral perfusion, in
      these patients.

PMID- 11234972
TI  - Enzootics of Leptospira abortions in Danish sow herds practising loose housing on
      deep straw bedding.

PMID- 11234974
TI  - HIV-1 in placentas of untreated HIV-1-infected women in relation to viral
      transmission, infectious HIV-1 and RNA load in plasma.
AB  - The presence of HIV in the placenta was analysed in relation to virological and
      immunological factors and vertical transmission of HIV in 39 pregnancies between
      1989 and 1993 among 37 HIV-1-infected women without zidovudine prophylaxis. HIV-1
      was detected in 12 of 37 (31%) placentas by immunohistochemistry and in 3 of 18
      by PCR. Altogether 14/39 (36%) placentas bore evidence of HIV-1 infection,
      although there was no relation with the outcome of HIV infection in the child.
      Neither was there a relation between placental infection and either CD4 cell
      counts or HIV-1 RNA levels. However, HIV-1 was isolated from plasma in 20 of 39
      (50%) pregnancies, which was inversely related to the presence of HIV in the
      placenta. When HIV-1 was identified in the placenta, HIV-1 was isolated from
      plasma in 3/14 (21%) pregnancies, vs 17/25 (68%) when it was not (p = 0.01), with
      a relative risk of having a placenta positive for HIV of 3.9 in pregnancies with
      a negative plasma HIV isolation. This inverse relation may point to differences
      in tropism between HIV-1 in placenta and plasma. The results show that the
      placental barrier prevents HIV transmission, irrespective of whether HIV enters
      the placenta or not.

PMID- 11234975
TI  - Zanamivir: a rational approach to influenza B.
AB  - Influenza B viruses have co-circulated with the HIN1 and H3N2 subtypes of
      influenza A since 1977. Influenza A viruses are found in various animals, whereas
      influenza B viruses are probably restricted to humans. The lack of an animal
      reservoir means that the virus has no potential for genetic reassortment across
      species. In addition, influenza B viruses are more serologically homogeneous than
      influenza A viruses. Thus, the chance of influenza B causing a pandemic is much
      lower than that of influenza A. However, influenza B viruses are still a frequent
      cause of local disease outbreaks and epidemics as a result of antigenic drift.
      Any prophylactic or therapeutic measure must, therefore, be effective against
      both influenza A and B viruses. Zanamivir is the first widely approved
      neuraminidase inhibitor for the treatment of influenza. It is delivered directly
      to the primary site of viral replication, the respiratory tract, and is well
      tolerated and effective in the treatment of both influenza A and B. Data in
      prophylaxis are also encouraging. Zanamivir is the only drug proven to be
      clinically effective against both influenza A and B virus infections.

PMID- 11234976
TI  - Group A streptococcus clones causing repeated epidemics and endemic disease in
      intravenous drug users.
AB  - Clones of Group A streptococcus (GAS) may spread epidemically and may be
      associated with enhanced virulence. Sociodemographic and clinical
      characteristics, together with bacterial isolates, of 79 patients with GAS
      infection in the Berne region between January 1993 and February 1997 were
      analysed retrospectively. Using pulsed-field gel electrophoresis, most strains
      (71%) were found to belong to one of 12 clones. Clonal strains caused
      significantly more frequent skin abscesses and more severe invasive disease than
      non-clonal strains. The largest clone (M serotype 1) occurred endemically in non
      IVDU patients and caused severe disease in most. Three clones occurred almost
      exclusively among IVDUs: an M serotype 11 was associated with severe, endemic
      disease; the other 2 clones, both of M serotype 25, caused epidemics of needle
      abscesses. Epidemic and endemic spread of GAS clones among IVDUs may be more
      frequent than previously assumed.

PMID- 11234977
TI  - Primary cultures of human chondrocytes are susceptible to low inocula of
      Staphylococcus aureus infection and undergo apoptosis.
AB  - Hypocellularity after joint infection has been attributed to the cytotoxic
      effects of pus, which can cause necrosis of chondrocytes. In this study, primary
      cultures of human chondrocytes lost their viability and underwent necrosis
      rapidly with high inocula of Staphylococcus aureus infection. Chondrocytes were
      shown to undergo apoptosis with low inocula of Staphylococcus aureus or their
      culture ultrafiltrate. These findings further support the hypothesis that
      residual bacterial toxins or triggered apoptotic processes in chondrocytes
      participate in the pathogenesis of post-infectious arthropathy.

PMID- 11234978
TI  - Koch's dilemma revisited.
AB  - Robert Koch's description of the etiologic agent of tuberculosis on 24 March 1882
      made him the hero of tuberculosis research overnight. In 1890, at the 10th
      International Congress of Medicine in Berlin, he claimed that he had discovered a
      remedy for the disease. This announcement was received with great excitement by
      both the medical community and the public. Medical trials performed in the
      subsequent months failed, however, to reveal a protective effect of Koch's
      remedy. In contrast, the diagnostic potential of tuberculin is still used and
      valued nowadays. This short article discusses Koch's reasons for fighting for the
      success of his remedy.

PMID- 11234979
TI  - Comparison of PCR to histology for the diagnosis of invasive candidiasis in a
      murine model.
AB  - The ability of a PCR method to diagnose invasive candidiasis in comparison to
      histology was determined using a murine model. One hundred and sixty mice were
      divided into 16 groups of 10 mice each. One group served as a negative control
      while 15 groups were infected with Candida albicans. Of the infected groups, 14
      (A1-A7 and B1-B7) received fluconazole treatment. Surviving animals of group A1
      were killed on day 3, and animals of successive groups were sacrificed every
      other day thereafter. Fluconazole treatment was stopped in the corresponding B
      group. All surviving mice were killed on day 43. One hundred and thirty-eight
      mice were evaluable. Yeast were seen in the kidney specimens of 77 mice; 66/77 of
      these, plus an additional 7 histologically-negative mice, were positive by PCR.
      The sensitivity and specificity of the PCR test compared with histology were
      85.71% and 88.52%, respectively. In combination with blood cultures, PCR could be
      a useful diagnostic tool for invasive candidiasis in clinical settings.

PMID- 11234980
TI  - Acute cellulitis: an unusual manifestation of meningococcal disease.
AB  - We describe 2 patients who both developed cellulitis due to Neisseria
      meningitidis and review 8 other cases reported since 1966. Female patients
      outnumbered male patients by 8 to 2, and there were 5 children and 5 adults. Four
      cases were caused by the serogroup C meningococcus, 2 cases by serogroup B and 2
      others by serogroup Y (the nature of the meningococcal group was not available in
      2 cases). Diverse medical underlying conditions were present in 4 of the adult
      patients. The periorbital region (in all 5 children), limb (in 3 adults), neck
      (in 1 adult) and face and neck (in 1 adult) were the locations of the
      meningococcal cellulitis. In all 10 patients, a favorable clinical response to
      the antibiotic therapy was documented and no relapses occurred. These cases
      indicate that N. meningitidis should be considered as a causative agent of
      cellulitis in the appropriate clinical setting, particularly in children with
      signs of periorbital infection or adults with underlying diseases.

PMID- 11234981
TI  - Amniotic fluid microflora in asymptomatic women at mid-gestation.
AB  - The presence and composition of amniotic fluid (AF) microflora, as well as AF
      glucose concentration and white blood cell (WBC) count, were investigated in 22
      consecutive asymptomatic women with intact membranes at mid-gestation. AF was
      retrieved by trans-abdominal amniocentesis. Three of the 22 women (13.6%) had
      microorganisms in their AF: Chlamydia trachomatis in 2 and both Corynebacterium
      group absolute nonfermenter (ANF) group and Propionibacterium spp. in 1. No
      differences were found in clinical characteristics, glucose concentration or WBC
      count in patients with and without microorganisms in their AF.

PMID- 11234982
TI  - Antibiotic guidelines lead to reductions in the use and cost of antibiotics in a
      university hospital.
AB  - The object of this study was to improve the use of antibiotics at Aker University
      Hospital, a 600-bed university hospital. We developed and implemented guidelines
      for antibiotic treatment and prophylaxis. We describe the impact of these
      guidelines on the use and cost of antibiotics and evaluate compliance with the
      guidelines. From 1994 to 1996 there was an 11% reduction in the use of
      antibacterial agents and a 42% reduction in the use of antifungal agents. The use
      of broad-spectrum antibiotics was reduced by 23%. The use of penicillin V and G
      increased by 5%, dikloxacillin/kloxacillin by 46% and erythromycin by 33%.
      Compared with 1994 values there was a 27% reduction in antibiotic costs in 1995,
      amounting to US$ 319,300, and a 32% reduction in antibiotic costs in 1996,
      amounting to US$ 380,000. A point-prevalence investigation conducted 18 months
      after the introduction of the guidelines indicated that compliance was > 95%. It
      proved possible to reduce the use of broad-spectrum antibacterial and antifungal
      agents, with significant cost savings. Point-prevalence studies may be a useful
      tool to detect deviations from guidelines and provide physicians with educational
      feedback.

PMID- 11234984
TI  - A case of prosthetic mitral valve endocarditis caused by Brucella abortus.
AB  - Endocarditis is a rare but serious complication of brucellosis. We report here a
      case of Brucella abortus endocarditis occurring on a prosthetic mitral valve. The
      diagnosis was established by positive serology, the presence of vegetation on the
      mitral prosthesis and isolation of B. abortus from the blood and valve cultures.
      The patient was successfully treated with combined medical and surgical therapy.

PMID- 11234983
TI  - Liver abscess caused by Clostridium difficile.
AB  - We report the first case of an infected cyst and liver abscess caused by
      Clostridium difficile. It recurred 11 months later, despite therapy with
      vancomycin and percutaneous drainage. Administration of metronidazole following
      percutaneous drainage achieved a favorable outcome.

PMID- 11234985
TI  - Human granulocytic ehrlichiosis--a clinical case in Scandinavia.
AB  - A clinical case of human granulocytic ehrlichiosis in Scandinavia is presented.
      The patient developed high fever, myalgia, headache and dyspnoea. Doxycycline
      treatment resulted in a dramatic improvement. Laboratory confirmation included a
      fourfold change in anti-Ehrlichia equi IFA titre and a positive PCR confirmed by
      gene sequence analysis.

PMID- 11234986
TI  - Anisakiasis presenting as an obstructive duodenal tumor. A Scandinavian case.
AB  - A case of chronic anisakiasis presenting as an occluding duodenal tumor is
      described. Significant falls in Anisakis simplex-specific serum IgE and total IgE
      occurred after resection of the lesion. Histopathologic examination showed a
      chronic eosinophilic granulomatous infiltrate and a tubular sclerotic structure
      in the antral submucosa consistent with, but not diagnostic for, an A. simplex
      larva.

PMID- 11234987
TI  - Fetal death associated with asymptomatic intrauterine Candida albicans infection
      and a retained intrauterine contraceptive device.
AB  - We present a case of intrauterine fetal death at 18 weeks of gestation associated
      with a retained intrauterine contraceptive device and asymptomatic intraamniotic
      and fetal infection by Candida albicans. The infection was verified by
      histopathologic examination of the placenta and umbilical cord, growth of C.
      albicans in samples of amniotic fluid and the presence of high levels of IL-6 in
      the amniotic fluid.

PMID- 11234989
TI  - First emergence of glycopeptide-resistant enterococci infections in Greece.

PMID- 11234988
TI  - Paradoxical emergence of humerus osteomyelitis during treatment of pulmonary and
      lymph-node tuberculosis.

PMID- 11234990
TI  - The tuberculosis pandemic today: routes of transmission and new target groups.
AB  - Tuberculosis, a disease that has been with us since the dawn of time, shows
      little sign of disappearing. Declines in death rates observed for several
      centuries prior to 1960 have been reversed in recent decades. This is in spite of
      the fact that efficient means of controlling the disease have been available
      during this period. This article reviews experience in 3 communities: among the
      Inuit, who live in the region of the North Pole; in the Beijing Municipality in
      the People's Republic of China; and in a socially isolated community in South
      Africa. In the first 2 communities, dramatic declines in the burden of disease
      have been observed: in the Inuit community, this occurred after substantial
      intervention; in the Beijing Municipality it was done with limited resources. The
      third community in South Africa illustrates an alarming trend, with tuberculosis
      being seen in a variety of locations but in the absence of external agents such
      as HIV infection. Clearly we need to refocus our efforts to control this disease,
      making use of the new tools that are rapidly becoming available. This must be
      done without delay, before influences such as HIV infection put the possibility
      of control completely out of reach.

PMID- 11234991
TI  - Protective effect of folic acid against oxidative stress produced in 21-day
      postpartum rats by maternal-ethanol chronic consumption during pregnancy and
      lactation period.
AB  - In this paper we show the protective effect of folic acid on oxidative stress in
      offspring caused by chronic maternal ethanol consumption during pregnancy and the
      lactation period. Glutathione reductase (GR) specific activity was assayed in
      liver and pancreas of offspring and mothers. In the offspring, these tissues were
      also assayed for markers of oxidative damage to lipids and proteins. The results
      show that ethanol exposure during pregnancy and lactation increased the specific
      activity of GR in tissues of the mothers (32-34% increase) as well as in the
      liver of their progeny (24%). Thiobarbituric acid reactive substances (TBARS)
      were also increased in the liver and pancreas of 21-day-old rats (37- and 54%,
      respectively). Alcohol also increased the amount of carbonyl groups in proteins
      in both tissues. These measures of ethanol-mediated oxidative stress were
      mitigated when pregnant rats were treated with folic acid concomitantly to
      ethanol administration. The antioxidant capacity of folic acid seems to be
      involved in its protective effect. The results obtained in the present work
      suggest that folic acid may be useful in the prevention of damage and promotion
      of health of the progeny of ethanol-treated rats.

PMID- 11234992
TI  - Genistein prevents the glucose autoxidation mediated atherogenic modification of
      low density lipoprotein.
AB  - Hyperglycemia has been assumed to be responsible for oxidative stress in
      diabetes. In this respect, glucose autoxidation and advanced glycation end
      products (AGE) may play a causal role in the etiology of diabetic complications
      as e.g. atherosclerosis. There is now growing evidence that the oxidative
      modification of LDL plays a potential role in atherogenesis. Glucose derived
      oxidants have been shown to peroxidise LDL. In the present study, genistein, a
      compound derived from soy with a flavonoid chemical structure (4', 5, 7
      trihydroxyisoflavone) has been evaluated for its ability to act as an antioxidant
      against the atherogenic modification of LDL by glucose autoxidation radical
      products. Daidzein, (4',7-dihydroxyisoflavone) an other phytoestrogen of soy, was
      tested in parallel. Genistein--in contrast to daidzein--effectively prevented the
      glucose mediated LDL oxidation as measured by thiobarbituric acid-reactive
      substance formation (TBARS), alteration in electrophoretic mobility, lipid
      hydroperoxides and fluorescence quenching of tryptophan residues of the
      lipoprotein. In addition the potential of glucose-oxidized LDL to increase tissue
      factor (TF) synthesis human endothelial cells (HUVEC) was completely inhibited
      when genistein was present during LDL oxidative modification by glucose. Both
      phytoestrogens did not influence the nonenzymatic protein glycation reaction as
      measured by the in vitro formation of glycated LDL. As the protective effect of
      genistein on LDL atherogenic modification was found at glucose/genistein molar
      ratios which may occur in vivo, our findings support the suggested beneficial
      action of a soy diet in preventing chronic vascular diseases and early
      atherogenic events.

PMID- 11234993
TI  - Contribution of haemoglobin and membrane constituents modification to human
      erythrocyte damage promoted by peroxyl radicals of different charge and
      hydrophobicity.
AB  - We have investigated the influence of the free radical initiator characteristics
      on red blood cell lipid peroxidation, membrane protein modification, and
      haemoglobin oxidation. 2,2'-Azobis(2-amidinopropane) (AAPH) and 4,4'-azobis(4
      cyanovaleric acid) (ACV) were employed as free radical sources. Both azo
      compounds are water-soluble, although ACV presents a lowed hydrophilicity,
      evaluated from octanol/water partition constants. At physiological pH, they are a
      di-cation and a di-anion, respectively. AAPH and ACV readily oxidise purified
      oxyhemoglobin in a very efficient free radical-mediated process, particularly for
      ACV-derived radicals, where nearly one heme moiety was modified per radical
      introduced into the system, suggesting that negatively charged radicals react
      preferentially at the heme group. The radicals derived from both azo-compounds
      lead to different oxidation products. Methemoglobin, hemichromes and choleglobin
      were produced in AAPH-promoted hemoglobin oxidation, while ACV-derived radicals
      predominantly form hemichromes, with very low production of choleglobin. Red cell
      damage was evaluated at the level of hemoglobin and membrane constituents
      modification, and was expressed in terms of free radical doses. Before the onset
      of the lytic process, ACV leads to more lipid peroxidation than AAPH, and induces
      a moderate oxidation of intracellular Hb. This intracellular oxidation is
      markedly increased if ACV hydrophilicity is decreased by lowering the pH. On the
      other hand, AAPH-derived radicals are considerable more efficient in promoting
      protein band 3 modification and cell lysis, without significant intracellular
      hemoglobin oxidation. These results show that the lytic process is not triggered
      by lipid peroxidation or hemichrome formation, and suggest that membrane protein
      modification is the relevant factor leading to red blood cell lysis.

PMID- 11234994
TI  - Protective effects of fluvastatin against reactive oxygen species induced DNA
      damage and mutagenesis.
AB  - Oxidative stress may be an important factor in the development of diabetic
      complications. Advanced glycation end-products have drown attention as potential
      sources of oxidative stress in diabetes. We investigated the protective effects
      of fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on
      oxidative DNA damage from reactive oxygen species or advanced glycation end
      products in vitro, as well as effects of main fluvastatin metabolites and other
      inhibitors of the same enzyme, pravastatin and simvastatin. Protective effects
      were assessed in terms of the DNA breakage rate in a single-stranded phage DNA
      system in vitro. DNA was exposed to either reactive oxygen species or advanced
      glycation end-products. Fluvastatin and its metabolites showed a strong
      protective effect comparable to those seen with thiourea and mannitol, though
      pravastatin and simvastatin did not exert clear protective effects. Furthermore,
      fluvastatin reduced the mutagenesis by reactive oxygen species or advanced
      glycation end-products in Salmonella typhimurium test strains. Both pravastatin
      and simvastatin still lacked protective activity. Fluvastatin and its metabolites
      protect against oxidative DNA damage and may reduce risk of consequent diabetic
      complications.

PMID- 11234996
TI  - Iron-induced oxidative damage in colon carcinoma (Caco-2) cells.
AB  - Intestinal epithelial cells have an active apical iron uptake system that is
      involved in the regulated absorption of iron. By the action of this system,
      intestinal cells acquire increasing amounts of iron with time. Since
      intracellular reactive iron is a source of free radicals and a possible cause of
      colon carcinoma, this study analyzed the oxidative damages generated by iron
      accumulation in Caco-2 cells. Cells cultured with increasing concentrations of
      iron increased both total intracellular iron and the reactive iron pool, despite
      an active IRE/IRP system, which regulates intracellular iron levels. Increasing
      concentrations of iron resulted in increased protein oxidative damage, as shown
      by the immunoreactivity for 4-hydroxy-2-nonenal-modified proteins, and markedly
      induced DNA oxidation determined by 8-hydroxy-2'-deoxyguanidine production. Iron
      also impaired cell viability, resulting in increased cell death after 6 days of
      culture. In summary, iron accumulation by intestinal Caco-2 cells correlated with
      oxidative damage to proteins and DNA. Oxidative damage finally resulted in loss
      of cell viability. The Fe-induced oxidative damage observed may be relevant in
      understanding the cascade of events associated with iron-mediated colon
      carcinogenesis.

PMID- 11234995
TI  - Oxidative insult in sheep red blood cells induced by T-butyl hydroperoxide: the
      roles of glutathione and glutathione peroxidase.
AB  - Three different types of red blood cells (RBC) were used: (i) RBC from sheep
      having genetically high GSH (ii) RBC from sheep with genetically low GSH and
      (iii) RBC from high-GSH sheep treated with CDNB to deplete GSH. Incubation of
      these RBC with t-butyl hydroperoxide (tBHP, 3 mM) for 10 min caused the formation
      of TBARS, oxidation of haemoglobin and degradation and aggregation of membrane
      proteins in RBC from low-GSH sheep and GSH-depleted RBC. By contrast, RBC from
      high-GSH sheep (normal RBC) did not show the degradation and aggregation of
      membrane proteins within the first 10 min. Dithiothreitol (DTT) was highly
      effective in preventing the tBHP-mediated oxidation of haemoglobin, the formation
      of TBARS and the degradation and aggregation of membrane proteins in both normal
      RBC and low-GSH RBC. However, DTT did not provide protection in GSH-depleted RBC
      or normal RBCs in the presence of 1.5 mM mercaptosuccinate (MCS), a potent
      inhibitor of GSH peroxidase (GSHPx). The ability of GSH to prevent the oxidation
      of haemoglobin and the degradation and aggregation of membrane proteins was
      abolished in the presence of MCS. These results indicate that the protective
      function of DTT involves a GSH-dependent mechanism. Both GSH and GSHPx play key
      roles in this enzymatic system. In the light of the complete protection of RBC
      against oxidation induced by tBHP in the presence of DTT or GSH, the GSH/GSHPx
      system appears to act directly as a tBHP scavenger. The activities of four well
      known antioxidants, Butylated hydroxytoluene, ascorbate, alpha-tocopherol and
      desferrioxamine were also tested in this study to cast further light on the role
      of free radical scavenging in protection from tBHP mediated free radical insult.

PMID- 11234997
TI  - The antioxidant effect of DL-alpha-lipoic acid on copper-induced acute hepatitis
      in Long-Evans Cinnamon (LEC) rats.
AB  - The Long-Evans Cinnamon (LEC) rats, due to a genetic defect, accumulate excess
      copper (Cu) in the liver in a manner similar to patients with Wilson's disease
      and spontaneously develop acute hepatitis with severe jaundice. In this study we
      examined the protective effect of DL-alpha-Lipoic acid (LA) against acute
      hepatitis in LEC rats. LA was administered to LEC rats by gavage in doses of 10,
      30 and 100 mg/kg five times per week, starting at 8-weeks-old and continuing till
      12-weeks-old. Although LA had little effect against the increases in serum
      transaminase activities, it suppressed the loss of body weight and prevented
      severe jaundice in a dose-dependent manner. Antioxidant system analyses in liver
      showed that LA treatment significantly suppressed the inactivations of catalase
      and glutathione peroxidase, and the induction of heme oxygenase-1, an enzyme
      which is inducible under oxidative stress. Furthermore, LA showed dose-dependent
      suppressive effect against increase in nonheme iron contents of both cytosolic
      and crude mitochondrial fractions in a dose-dependent manner. Although at the
      highest dose, LA slightly suppressed the accumulation of Cu in crude
      mitochondrial fraction, it had no effect on the accumulation of Cu in cytosolic
      fraction. While LA completely suppressed the increase in lipid peroxidation (LPO)
      in the microsomal fraction at the highest dose, the suppressive effect against
      LPO in crude mitochondrial fractions was slight. From these results, it is
      concluded that LA has antioxidant effects at the molecular level against the
      development of Cu-induced hepatitis in LEC rats. Moreover, mitochondrial
      oxidative damage might be involved in the development of acute hepatitis in LEC
      rats.

PMID- 11234998
TI  - ESR detection of intraphagosomal superoxide in polymorphonuclear leukocytes using
      5-(diethoxyphosphoryl)-5-methyl-l-pyrroline-N-oxide.
AB  - We applied a spin trap, 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline-N-oxide
      (DEPMPO), to detect O2*- generation during phagocytosis in human
      polymorphonuclear leukocytes (PMNs). PMNs were activated with serum-opsonized
      zymosan (sOZ) in the presence of DEPMPO. The ESR spectra mainly consisted of
      Cu,Zn-SOD-sensitive DEPMPO-OOH spin adducts. To clarify where these spin-adducts
      were present, cells after stimulation were separated from extracellular fluid by
      brief centrifugation and resuspended in Hanks' balanced salt solution. ESR
      examination showed that DEPMPO-OOH adducts were present in both fractions. When
      cells were stimulated by phorbol myristate acetate (PMA), the DEPMPO-OOH was
      detected in extracellular fluid but not in the cell fraction. Furthermore, DEPMPO
      OOH adducts were quickly converted into ESR-silent compounds by addition of cell
      lysate of PMNs. These results indicate that DEPMPO is useful to detect O2*- of
      extracellular space including the intraphagosome but not that of intracellular
      space in sOZ-stimulated phagocytes.

PMID- 11234999
TI  - Increase in nuclear calcium in smooth muscle cells exposed to oxidized low
      density lipoprotein.
AB  - Vascular smooth muscle cells respond with an increase in intracellular Ca2+
      within seconds after exposure to oxidized low density lipoprotein (oxLDL). This
      has been suggested to represent a signaling response that may have implications
      for gene expression. If so, oxLDL may induce increases in nuclear Ca2+ in smooth
      muscle cells in response to oxLDL. Aortic smooth muscle cells were exposed to 100
      microg/ml oxLDL. Large, rapid increases in [Ca2+]i were observed using fluo-3 as
      an indicator dye to detect intracellular Ca2+ on the stage of a confocal
      microscope. This was also confirmed using ratiometric imaging of indo signals.
      These elevations appeared to be localized to the nuclear region of the cell. DNA
      staining of the cells confirmed its localization to the nuclear/perinuclear
      region of the cell. Our data demonstrate that oxLDL induces a nuclear localized
      elevation in Ca2+i that may have important implications for nuclear function.

PMID- 11235000
TI  - Daily cocoa intake reduces the susceptibility of low-density lipoprotein to
      oxidation as demonstrated in healthy human volunteers.
AB  - Nine male volunteers were given 36 g of cocoa powder (containing 2610 mg of
      polyphenols) per day with sugar and 6 volunteers received an equivalent amount of
      sugar for 2 weeks. Conjugated diene production in LDL induced by 2-2' azobis(4
      methoxy-2,4-dimethylvaleronitrile) (V-70) and copper ion were evaluated. The lag
      time was significantly prolonged at 1 and 2 weeks in V-70 and at 2 weeks in
      copper ion after cocoa powder consumption. The level of excretion of epicatechin
      in urine was significantly higher in the cocoa group than that in the control
      group. In conclusion, the antioxidants in cocoa powder might be absorbed and
      increase the resistance of human LDL to oxidation.

PMID- 11235001
TI  - Sir William Refshauge Lecture 1999. Drugs and nutrition.

PMID- 11235002
TI  - Power output of legs during high intensity cycle ergometry: influence of hand
      grip.
AB  - Indices of mechanical power output were obtained from twelve subjects during high
      intensity leg cycle ergometry tests (20 second duration; 75 grams per kilogram
      total body mass) using two protocols: one with a standard handle-bar grip (with
      grip), and one with supinated wrists (without-grip). Peak mechanical power, mean
      mechanical power, fatigue index and total mechanical work values were calculated
      for each subject during each test, and the sample mean differences associated
      with the two protocols were compared using paired Student t-tests. The with-grip
      protocol yielded significantly greater peak mechanical power output and greater
      fatigue index than the without-grip protocol (886 +/- 124W and 815 +/- 151W,
      respectively; and 35 +/- 10% and 25 +/- 8%, respectively; p<0.01). The electrical
      activity of the anterior forearm musculature was measured in the twelfth subject
      during the performance of each of the test protocols. While peak mechanical power
      output was greater during the with-grip protocol, than during the without-grip
      protocol, the electromyographs showed much greater forearm muscle activity during
      the with-grip protocol. Thus the protocol which allowed for the greatest measure
      of peak leg power output was also associated with considerable arm muscle
      activity. These findings should be considered when biochemical and physiological
      measurements are obtained from arm blood samples.

PMID- 11235003
TI  - Nutrition for the Australian Rules football player.
AB  - This review summarises past and present nutritional practices of Australian Rules
      Football players, noting changes that have occurred as the footballers have
      become more receptive to scientific input. Australian Rules Football is a unique
      sport, with matches involving intermittent high intensity sprints between periods
      of jogging and walking and repeated physical contact. Endurance, speed, strength,
      power and agility are essential physical characteristics. Australian Rules
      footballers exhibit a wide range of anthropometrical attributes due to the
      positional requirements of the game. Dietary surveys indicate that footballers of
      the 1980's consumed a diet similar to that of the general Australian population
      consisting of 44%, 37.5%, 15% and 3.5% of carbohydrate (CHO), fat, protein and
      alcohol, respectively. However, as dietitians are becoming an integral part of
      the support staff of teams there is evidence that nutritional practices conducive
      to optimal sporting performance are now being followed. Due to the prolonged
      duration and intermittent high intensity activity pattern of Australian Rules,
      nutritional supplementation such as fluid and CHO intake during training and
      competition and creatine intake may be beneficial; however, further research
      needs to be conducted in the field to determine its importance in Australian
      Rules Football.

PMID- 11235004
TI  - Changes in blood coagulation and fibrinolysis associated with maximal exercise
      and physical conditioning in women taking low dose oral contraceptives.
AB  - Blood coagulation parameters (thromboplastin time. PT; activated partial
      thromboplastin time, aPTT; fibrinogen; antithrombin III, ATIII; von Willebrand
      factor-concentration, vWF; factor VIII-activity, FVIII) and fibrinolytic
      parameters (plasminogen; (alpha-antiplasmin; euglobulin-lysis-time, Elt; tissue
      plasminogenactivator-antigen, tPA-antigen; plasminogenactivator-1-antigen, PAI-1
      antigen) were evaluated in 34 women on low-dose oral contraceptives (OC) twice at
      intervals of 12 weeks each time before and after maximal exercise. During the 12
      weeks, 24 women took part in an aerobic conditioning program and 10 women were
      requested to avoid any kind of sports activity for this period. Blood samples
      were taken before training and before and after maximal treadmill exercise. This
      procedure was repeated after the training program. After maximal exercise we
      found a significant reduction of aPTT and PT (increase in %), a decrease in
      ATIII, vWF, fibrinogen, plasminogen and alpha2-antiplasmin but an increase in
      fibrinolytic activity (all p<0.05). Maximal exercise is associated with an
      increase in blood coagulation and fibrinolysis also in women taking OC. After the
      physical conditioning program an increase in fibrinolytic activity at rest was
      noted in the training group. Opposed to that the fibrinolytic activity at rest
      decreased in the control group after abstinence of sports activity over this
      period (p<0.05, MANOVA).

PMID- 11235005
TI  - Predicting success in junior elite basketball players--the contribution of
      anthropometic and physiological attributes.
AB  - Talent identification programs have traditionally focused on individual sports
      with discrete physical and physiological characteristics. Limited attention has
      been directed toward predicting performance in team sports. This study measured
      anthropometric and physiological attributes of 125 male and 123 female junior
      basketball players competing at the Australian Under 16 championships in 1998. In
      addition, experienced coaches rated the performance of players during the
      championships. Performance profiles were compared across playing positions and by
      playing performance ('Best versus Rest'). Differences in anthropometric
      characteristics were present across some playing positions for both males and
      females. Speed and agility differences between some playing positions were also
      present. Best players differed to Rest players on a number of anthropometric and
      physiological variables for both males and females. Regression analyses indicated
      the test variables accounted for a significant proportion of variance in playing
      performance for both females (41.3%) and males (38.3%). A Z score analysis
      indicated good alignment between the test and coach ranking of the Best player in
      four out of five positions for females and two out of five positions for males.
      Anthropometric and physiological profiling can contribute to selection procedures
      in junior basketball, however determinants of success are multi-factorial.

PMID- 11235006
TI  - A preliminary investigation of injury prevention strategies in Netball: are
      players heeding the advice?
AB  - All netball players who sought treatment for injury during the three-day 1995 New
      South Wales State Netball Championships were surveyed. Of 940 participants, 131
      incurred injuries (139.4 injuries per 1,000 players; 23.8 injuries per 1,000
      playing hours). Ankle and knee injuries were most frequent, with ligament
      sprains, bruising/contusions, and muscle strains presenting as the most common
      injury types. The most frequent causes of injury were incorrect landings,
      collisions with players, being struck by the ball, or repetitive movements.
      Although most players heeded advice pertaining to warm-up, occurrence of injuries
      during warm-up and cool-down suggested that activities performed during these
      periods may be inappropriate. To reduce risk of ankle ligament sprain in netball,
      high-cut netball shoes have been advocated. However, only 5.1% of players
      surveyed wore high-cut shoes. Furthermore, although players have been advised to
      seek immediate treatment when injured, 54.7% of players finished the game before
      seeking treatment. Relative to previous netball injury investigations, the
      frequency and nature of injuries, and the injury prevention behaviours of players
      have not changed. Therefore, wider promotion of injury prevention resources,
      combined with research into the effectiveness of these resources and how players
      can be encouraged to adopt appropriate injury prevention strategies in netball,
      is recommended.

PMID- 11235007
TI  - The bioenergetics of World Class Cycling.
AB  - Professional cycle racing is one of the most demanding of all sports combining
      extremes of exercise duration, intensity and frequency. Riders are required to
      perform on a variety of surfaces (track, road, cross-country, mountain), terrains
      (level, uphill and downhill) and race situations (criterions, sprints, time
      trials, mass-start road races) in events ranging in duration from 10 s to 3 wk
      stage races covering 200 m to 4,000 km. Furthermore, professional road cyclists
      typically have approximately 100 race d/yr. Because of the diversity of cycle
      races, there are vastly different physiological demands associated with the
      various events. Until recently there was little information on the demands of
      professional cycling during training or competition. However, with the advent of
      reliable, valid bicycle crank dynanometers, it is now possible to quantify real
      time power output, cadence and speed during a variety of track and road cycling
      races. This article provides novel data on the physiological demands of
      professional and world-class amateur cyclists and characterises some of the
      physiological attributes necessary for success in cycling at the elite level.

PMID- 11235008
TI  - Technique and timing in the womens forward two and one half somersault pike and
      mens three and one half somersault pike 3m springboard dives.
AB  - The purpose of this study was to compare the forward two and one half somersault
      dive in a pike position (105B) performed by females (n=25) and the forward three
      and one half somersault dive in a pike position (107B) performed by males (n=25)
      to determine changes required by females to successfully perform 107B. Video data
      of the dives performed at the 1999 FINA World Diving Cup were captured and
      digitised to obtain times and postures of the divers at specific events including
      hurdle landing, takeoff, and entry. Estimates of hurdle flight height and mass
      normalised work done on the springboard were obtained from hurdle and flight
      times. Females performing 105B had significantly less hip and knee flexion at
      landing from the hurdle than males performing 107B. It is known from simulations
      that the ability to land in a very flexed position without absorbing energy
      depends on the ability to generate large extension torques at landing. Therefore,
      it is likely that females need to increase strength to successfully complete
      107B.

PMID- 11235009
TI  - Comparing wobble board and jump-landing training effects on knee and ankle
      movement discrimination.
AB  - The effects of two training programs on movement discrimination ability, at the
      ankle and knee, were assessed from the left and right lower limbs of forty-four
      football players. All players in three Under 18 Victorian Football League (VFL)
      squads were allocated to either wobble board training, jump landing training, or
      no-training conditions. Pre-tests to assess discrimination of extent for active
      movements made while standing were carried out on both ankles and knees of all
      subjects, using an automated device to accurately set the different movement stop
      points. Five distances were used, between 10.5 degrees and 14.5 degrees from
      horizontal for ankle inversion, and between 30.3 degrees and 31.7 degrees from
      vertical for knee flexion. From a series of 50 inversion movements and 50 knee
      flexion movements, matrices of absolute judgement by actual movement extent were
      produced. Non-parametric signal detection analysis was applied to the
      discrimination score. All subjects were retested after eight weeks. Improvement
      in discrimination of ankle movements into inversion from pre-test (0.65) to post
      test (0.70) for the wobble board trained group was significantly larger than the
      change in the jump-landing trained and the untrained groups (Jump Landing:
      Pretest: 0.64 to Post-test: 0.64 and Control; Pretest: 0.63 to Post-test: 0.64).
      Discrimination of knee flexion movements improved significantly from pre-test to
      post-test in all three groups. These data demonstrate that wobble board training
      can improve discrimination of discrete ankle inversion movements, an effect
      interpreted as enabling greater accuracy in the making of inversion movements in
      foot preparation prior to ground contact.

PMID- 11235010
TI  - Response timing and muscular coordination in fencing: a comparison of elite and
      novice fencers.
AB  - Reaction time (RT), movement time (MT), total response time (RMT) and accuracy of
      elite and novice fencers was studied under three levels of target choice (single
      , two- and four-targets) with three variations of movement distance (short,
      medium and long lunge). In addition, electromyographic activity (EMG) of selected
      upper and lower limb muscles was used to compare the two groups. The elite
      subjects were faster for RT and RMT and displayed a higher level of accuracy. The
      hypothesis that increasing choice would cause increases in RT was not upheld.
      Except for some differentiation between the short and the two longer distances,
      the effects of movement distance were not marked. Qualitative and quantitative
      analysis of EMG revealed the high consistency of response patterns within
      subjects and highlighted the synergistic roles of selected muscles in
      distinguishing between elite and novice fencers. These findings confirm that
      differences in the technical skill of fencers can be distinguished in the
      laboratory through a combination of response timing measures in association with
      measures of muscle action. They also draw attention to practical implications for
      individual skill assessment and training. Analysis of pre-movement muscle
      activity provided moderate support for the hypothesis that it was part of a
      single control process and indicates that a dual process can involve both the
      maintenance of postural stability and the generation of movement. It is suggested
      that different movement contexts can lead to different levels of coordination
      between the system controlling posture and that controlling movement.

PMID- 11235011
TI  - Metabolic responses to prolonged work during treadmill and water immersion
      running.
AB  - The primary aim of this study was to compare the physiological responses to
      prolonged treadmill (TM) and water immersion to the neck (WI) running at
      threshold intensity. Ten endurance runners performed TM and WI running VO2max
      tests. Subjects completed submaximal performance tests at ventilatory threshold
      (Tvent) intensities under TM and WI conditions and responses at 15 and 42 minutes
      examined. VO2 was lower in WI (p<0.05) at maximal effort and Tvent. The Tvent VO2
      intensities interpolated from the TM and WI VO2max tests were performed in both
      TM (i.e., TM@TM(tvent),TM@WI(tvent), corresponding to 77.6 and 71.3% respectively
      of TM VO2max) and WI conditions (i.e., WI@TM(tvent), WI@WI(tvent), corresponding
      to 85.5% and 78.2% respectively of WI VO2max). Each of the dependent variables
      was analyzed using a 3-way repeated measures ANOVA (2 conditions X 2 exercise
      intensities X 7 time points during exercise). VO2max values were significantly
      lower in the WI (52.4(5.1) ml.kg(-1) min(-1)) versus TM (59.7(6.5) ml.kg(-1) min(
      1)) condition. VO2 during submaximal tests were similar during the TM and WI
      conditions. HR and [BLa] responses to exercise at and above WI(tvent) were
      similar during short-term exercise, but values tended to be lower during
      prolonged exercise in the WI condition. There were no statistical differences in
      VE responses in the 2 conditions, however as with HR and [BLa] an upward trend
      was noted with TM exercise over the 42 minute duration of the tests. RPE at
      WI(tvent) was similar for TM and WI exercise sessions, however, RPE at TM(tvent)
      was higher during WI compared to TM running. Cardiovascular drift was observed
      during prolonged TM but not WI running. Results suggest differences in metabolic
      responses to prolonged submaximal exercise in WI, however it can be used
      effectively for cross training.

PMID- 11235012
TI  - Awareness of and attitudes to the new physical activity recommendations-
      perceptions of attenders of the 5th IOC World Congress on Sport Science.
AB  - New evidence suggests that regular moderate intensity physical activity confers
      substantial health benefits. This information needs to be conveyed to exercise
      and sports professionals, as they have a potential lead role in broader public
      education to encourage physical activity. This study reports data from a survey
      of attenders at a sports medicine/sports science conference in Sydney in November
      1999. Of the 292 who responded, only one third had ever heard of the United
      States Surgeon General's report on physical activity and health, and 43% had
      heard of the Active Australia initiative. Those who were members of Sports
      Medicine Australia (SMA), female or younger responders were more likely to recall
      Active Australia. An understanding of the moderate physical activity message was
      highest among sports physicians, and those who already perceived physical
      activity advice to be part of their role, and lowest among exercise and posrts
      scientists. The study suggests the need for professional education strategies to
      be developed in this area for exercise and sports scientists.

PMID- 11235013
TI  - Kenyan runners from the Rift Valley (2,000 metres above sea level) have dominated
      world middle and endurance events for thirty years.

PMID- 11235014
TI  - Perspectives on East African middle and long distance running.

PMID- 11235015
TI  - Induction of IL-6 via the EP3 subtype of prostaglandin E receptor in rat adjuvant
      arthritic synovial cells.
AB  - OBJECTIVE AND DESIGN: This study investigated the role of the prostaglandin E
      receptor EP3 subtype in the development of inflammatory synovitis. MATERIALS AND
      METHODS: We examined the EP3 mRNA expression in the synovial tissue of rats with
      adjuvant arthritis and the effect of selective EP agonists on IL-6 production by
      cultured rat synovial cells. RESULTS: Of the two rat EP3 isoforms, rEP3B mRNA but
      not rEP3A mRNA was expressed in rat synovial cells. RT-PCR and ELISA were used to
      analyze the effects of selective EP3 agonist (ONO-AE-248) on IL-6 production by
      rat cultured synovial cells. This selective EP3 agonist induced IL-6 production
      by rat synovial cells in a time- and dose-dependent manner. CONCLUSIONS: Our
      results suggest that PGE2 upregulates IL-6 production by synovial macrophages and
      fibroblasts through rEP3B in rats with adjuvant arthritis.

PMID- 11235016
TI  - Anti-dsDNA antibody up-regulates interleukin 6, but not cyclo-oxygenase, gene
      expression in glomerular mesangial cells: a marker of immune-mediated renal
      damage?
AB  - OBJECTIVE AND DESIGN: To determine whether anti-double stranded DNA antibody
      (anti-dsDNA) can affect the synthesis of eicosanoids and cytokines in rat
      glomerular mesangial cells (RMC). MATERIALS OR SUBJECTS: Glomerular mesangial
      cells were isolated and subcultured from Sprague-Dawley rats. Monoclonal anti
      dsDNA (12B3 clone) was derived from autoimmune MRL-lpr/lpr mouse by hybridoma
      technology. METHODS: The mRNA expression of cyclo-oxygenase type 1 (COX-1), type
      2 (COX-2), Th1 (IL-2 and IFN-gamma)/Th2 (IL-4 and IL-10) and proinflammatory (IL
      6 and TNF-alpha) and anti-inflammatory (TGF-beta) cytokines of RMC +/- anti-dsDNA
      was detected by RT-PCR. The PGE2 production by RMC +/- anti-dsDNA was measured by
      ELISA. The statistical significance was assessed by non-parametric Wilcoxon
      signed rank test. RESULTS: We found RMC spontaneously expressed COX-1, but not
      COX-2. The incubation of RMC with anti-dsDNA (50 ng/ml) did not affect COX
      expression and PGE2 production by RMC. RMC also spontaneously expressed IL-6, TNF
      alpha and TGF-beta mRNA. However, only IL-6 was up-regulated by anti-dsDNA.
      CONCLUSIONS: Increased IL-6 expression in RMC may become a marker of anti-dsDNA
      mediated immune damage of mesangial cells.

PMID- 11235018
TI  - Anti-arthritic effects of KF20444, a new immunosuppressive compound inhibiting
      dihydroorotate dehydrogenase, on rat collagen-induced arthritis.
AB  - OBJECTIVE AND DESIGN: A newly synthesized inhibitor of pyrimidine de novo
      biosynthesis, KF20444 (6,7-dihydro-10-fluoro-3-(2-fluorophenyl)-5H-benzo [6,7]
      cyclohepta [1,2-b] quinoline-8-carboxylic acid), was evaluated as an inhibitor of
      dihydroorotate dehydrogenase (DHO-DHase) and tested in the rat collagen-induced
      arthritis (CIA) model. MATERIAL AND METHODS: Female Sprague Dawley rats, 5 weeks
      old, were used for evaluation of KF20444 in the CIA model. Arthritis was
      evaluated by arthritis score, serum anti-type II collagen antibody titer, body
      weight loss, radiographical and histological changes. TREATMENT: KF20444 was
      orally administered 5 times per week (0.3, 1, 3 mg/kg/day). RESULTS: KF20444
      inhibited rat liver dihydroorotate dehydrogenase in vitro with Ki = 8.5 +/- 3.2
      nM, which was a comparable effect to that of brequinar sodium (Ki = 25.3 +/- 5.3
      nM). The anti-proliferative effect of KF20444 was caused by cell cycle arrest at
      the S-phase. Treatment with 3 mg/kg/day of KF20444 completely prevented the
      development of CIA based on reduction of the arthritis score. The 50% effective
      dose (ED50) of KF20444 on arthritis score was 0.64 mg/kg. KF20444 ameliorated
      body weight loss associated with disease onset. The compound also inhibited the
      increase in serum anti-type II collagen antibody level, and reduced both pannus
      formation and bone erosion. Importantly, KF20444 suppressed the development of
      arthritis, even when it was administered after booster immunization of collagen.
      CONCLUSIONS: KF20444 is a novel immunosuppressant which inhibits DHO-DHase and
      its effects in CIA suggest that it could be useful in the treatment of rheumatoid
      arthritis.

PMID- 11235017
TI  - Hydrogen peroxide induces apoptosis of chondrocytes; involvement of calcium ion
      and extracellular signal-regulated protein kinase.
AB  - OBJECTIVE: Recent observations demonstrated that reactive oxygen species
      facilitate cartilage degradation. We demonstrated that hydrogen peroxide (H2O2)
      caused inhibition of proteoglycan synthesis, induction of apoptosis and
      stimulation of extracellular signal-regulated protein kinase (ERK) of the
      chondrocytes (Inflamm Res 48: 399-403, 1999). To determine whether activation of
      ERK is involved in the induction of chondrocyte apoptosis, we examined the signal
      transduction pathways in this hydrogen peroxide induced apoptosis. DESIGN: Bovine
      articular chondrocytes were cultured. To determine the induction of apoptosis,
      Annexin V staining and terminal deoxynucleotidyl transferase were used. The
      activity of caspase-3 was measured using an apopain assay kit. Intracellular Ca2+
      imaging was observed after fura2-AM loading. RESULTS: Hydrogen peroxide enhanced
      annexin V positive apoptotic cells and caspase-3 activity, which is an executor
      of apoptosis. Hydrogen peroxide also enhanced intracellular Ca2+ and
      preincubation with the intracellular Ca2+ chelator protected chondrocytes against
      hydrogen peroxide-induced cell apoptosis, indicating that an increase in the
      cytosolic Ca2+ plays a decisive role in this action. When ERK activity was
      blocked with geldanamycin and PD098059, increased apoptosis was evident.
      CONCLUSION: Hydrogen peroxide induces chondrocyte apoptosis via Ca2+ signaling,
      and ERK is involved in these signal transduction pathways.

PMID- 11235019
TI  - Adherence of eosinophils from allergic and normal ponies to cultured equine
      endothelial cells.
AB  - OBJECTIVES: To compare adherence of stimulated and unstimulated eosinophils from
      allergic and normal ponies to cultured equine vascular endothelial cells (equine
      digital vein endothelial cells; EDVEC) and examine the effect of eosinophil
      derived factor(s) on cell adherence. METHODS: Eosinophil adherence to
      unstimulated EDVEC or EDVEC pretreated with IL-1beta or supernatants from
      stimulated eosinophils was measured. Supernatants were also assayed for TNFalpha
      and IL-1beta-like bioactivity. RESULTS: Adherence of unstimulated and rhIL-5 (10
      ng/ml)-stimulated eosinophils from allergic ponies to rhIL-1beta-treated EDVEC
      was significantly greater than that of cells from normal ponies. Pretreatment of
      EDVEC with supernatants from stimulated eosinophils from both groups of ponies
      significantly increased adherence of autologous cells and IL-1beta- and TNFalpha
      like bioactivities were detected in the supernatants. CONCLUSIONS: Mediator
      induced activation of equine eosinophils may lead to further eosinophil
      recruitment by releasing cytokines that up-regulate endothelial cell adhesion
      molecule expression. Increased adherence of blood eosinophils from allergic
      ponies to stimulated endothelium could be explained by in vivo priming.

PMID- 11235020
TI  - Gc-globulin is an acute phase reactant and an indicator of muscle injury after
      spinal surgery.
AB  - OBJECTIVES AND DESIGN: Actin is the dominating protein in mammalian cells,
      including muscle cells, and is released into the circulation after tissue injury.
      Gc-globulin, one of the proteins in the Extracellular Actin Scavenger System
      (EASS) is responsible for the clearance of actin from the circulation. Clinical
      studies show that plasma levels of Gc-globulin are reduced in situations with
      tissue death, and that the degree of reduction correlates with development of
      organ dysfunction and survival. The purpose of the present study was to describe
      the serial changes in Gc-globulin after a standardized surgical procedure
      resulting in major muscle injury, comparing changes in Gc-globulin with changes
      in other acute phase proteins. MATERIAL AND METHODS: Twelve patients who
      underwent posterolateral lumbar fusion from L4 or L5 to sacrum were included in
      the study. Peripheral venous blood samples were obtained before surgery and on
      day 1, 3, 5, 12, 21, and 28 after surgery. Serum samples were analyzed for total
      Gc-globulin (Gc(total)), percentage of Gc-globulin complexed with actin
      (GC(complexed)), albumin, orosomucoid, haptoglobin, transferrin and creatin
      phosphokinase (CK). RESULTS: Gc(total) decreased to 87% of pre-operative values
      on day one. Thereafter the levels increased to a maximum of 135% of pre-operative
      values on day five, approaching baseline values towards the end of the
      observation period. Compared to this, changes in GC(complexed) displayed a mirror
      like time-course, with levels of Gc(total) and GC(complexed) being significantly
      inversely correlated on day one (P < 0.05). Levels of albumin remained below pre
      operative values the first three weeks post-operatively, reaching baseline at the
      end of the observation period (P < 0.05). CONCLUSION: The initial changes in Gc
      globulin can be explained by increased release of actin from injured muscle
      tissue. Subsequently Gc-globulin displays characteristics of a so-called positive
      acute phase reactant, supporting previous in vitro studies, and clinical studies
      after minor surgery. In spite of genetic linkage and structural homology Gc
      globulin and albumin are regulated differently after surgical trauma.

PMID- 11235021
TI  - Dithranol upregulates IL-10 receptors on the cultured human keratinocyte cell
      line HaCaT.
AB  - OBJECTIVE: Dithranol is highly effective in the treatment of psoriasis, however
      its mode of action is still not well known. Since interleukin-8 and interleukin
      10 are involved in the pathogenesis of psoriasis, the aim of our study was to
      investigate the effect of dithranol on interleukin-8, interleukin-10 mRNA
      production and interleukin-10 receptor expression of the HaCaT keratinocyte cell
      line which is commonly used in experiments examining the effects of therapeutic
      drugs on keratinocytes. MATERIALS AND METHODS: Cultured HaCaT cells were treated
      with 0.1-0.5 microg/ml dithranol for 30 minutes. After 2 and 4 h total cellular
      RNA isolated from HaCaT cells was reverse transcribed (RT) to cDNA which was
      subjected to polymerase chain reaction (PCR) with specific primer pairs for
      interleukin-8, interleukin-10 and interleukin-10 receptor. For
      immunohistochemistry cultured HaCaT cells were stained with a monoclonal antibody
      against the human interleukin-10 receptor. RESULTS: Our results showed that
      dithranol treatment did not change the highly elevated level of interleukin-8
      mRNA of HaCaT cells. Interleukin-10 mRNA signal with RT-PCR could not be detected
      in HaCaT cells. Depending on the concentration dithranol increased the mRNA
      production of interleukin-10 receptors in HaCaT cells. This dithranol induced
      dose dependent upregulation of IL-10 receptors in HaCaT cells was also observed
      on the protein level using immunohistochemistry. CONCLUSIONS: Since the
      interleukin-10 receptor expression of keratinocytes in psoriatic lesional skin is
      downregulated, the dithranol induced upregulation of the receptor in our model
      system might help to reveal the therapeutic action of the drug.

PMID- 11235022
TI  - Effects of COX-1 and COX-2 inhibitors on eicosanoid biosynthesis and the release
      of substance P from the guinea-pig isolated perfused lung.
AB  - OBJECTIVE: In the guinea-pig isolated perfused lung, co-administration of
      bradykinin (BK) and histamine causes the release of pro-inflammatory
      neuropeptides, an effect that is largely dependent on BK-induced formation of
      prostaglandins. Since it is known that at least two isoenzymes, cyclooxygenase-1
      (COX-1) and cyclooxygenase-2 (COX-2) catalyse the conversion of arachidonic acid
      to prostaglandins (PGs) and thromboxanes, the present study aimed at
      investigating the effect of selective COX-1 and COX-2 inhibitors on the evoked
      release of substance P (SP). MATERIAL AND METHODS: Lungs were vascularly perfused
      with oxygenated physiological salt solution containing peptidase inhibitors. BK
      (0.1 microM) and histamine (100 microM) were added to the perfusate for 10 min
      and 5 min, respectively. The concentrations of 6-keto-PGF1alpha, cysteinyl
      leukotriene (LT), and SP were determined in the outflow by radioimmunoassay.
      RESULTS: In non-stimulated preparations, indomethacin (2 microM) and the
      selective COX-1 inhibitor SC-560 (0.03-1 microM) reduced basal release of 6-keto
      PGF1alpha, without significantly affecting the release of cysteinyl-LT and SP.
      The selective COX-2 inhibitors NS-398 (1 microM) or DFU (10 microM) had no
      significant effect on the basal release of eicosanoids or SP. Co-administration
      of BK and histamine caused a pronounced increase in the concentration of 6-keto
      PGF1alpha and cysteinyl-LT, and SP in the effluate. Under these conditions,
      indomethacin as well as SC-560 reduced the release of 6-keto-PGF1alpha, enhanced
      cysteinyl-LT release, and attenuated the release of SP. In contrast, the
      selective COX-2 inhibitors NS 398 and DFU had no significant effect on the
      stimulated release of eicosanoids or SP. CONCLUSIONS: These results suggest that
      in the isolated guinea-pig lung, basal prostanoid biosynthesis as well as BK
      induced stimulation of prostanoid formation and subsequent facilitation of
      histamine-induced SP release is primarily mediated by COX-1 without detectable
      involvement of COX-2.

PMID- 11235023
TI  - Interaction between the adrenal and the pineal gland in chronic experimental
      inflammation induced by BCG in mice.
AB  - OBJECTIVE: To investigate the adrenal gland influence on diurnal rhythm of
      chronic inflammation induced by BCG in mice and its interaction with the pineal
      gland. METHODS: C57Bl/6 mice were injected with BCG in the footpad and maintained
      in a 12/12 h light-dark cycle. All the experimental manipulations were done after
      20-45 days. Paw swelling was measured every 4 h for 48 or 72 h and decomposed by
      Fourier transformation. Vascular permeability was evaluated by Evans Blue
      overflow, in mice killed at midday or midnight. 6-Sulphatoxymelatonin urine
      concentration was determined by radioimmunoassay in samples taken during the dark
      or light phase. RESULTS: Adrenalectomy or metyrapone treatment abolished the paw
      swelling diurnal rhythm, the nocturnal reduction in vascular permeability, and
      the nocturnal increase in 6-sulphatoximelatonin in the urine. Nocturnal
      administration of melatonin to adrenalectomized mice restored the paw swelling
      diurnal variation and the reduction of vascular permeability of the inflamed paw.
      CONCLUSION: Adrenal cortical hormones are important for the maintenance of the
      diurnal rhythm of chronic inflammation (paw swelling and vascular permeability),
      probably by promoting a nocturnal surge of melatonin, which is the hormone that
      modulates the diurnal variation of chronic inflammation.

PMID- 11235024
TI  - Solid-state 87Rb NMR study in powdered RbMnCl3.
AB  - Structural phase transition at 290 K and the implication on the intermediate
      phase above 290 K in powdered RbMnCl3 are observed by using a solid-state 87Rb
      NMR spectroscopy. Quadrupole coupling constants (e2qQ/h), the asymmetry
      parameters (eta), and the relative peak intensities for two physically
      nonequivalent Rb sites, Rb(I) and Rb(II), are determined from nonlinear least
      squares fits to the 87Rb NMR powder patterns in the temperature range from 260 to
      330 K. Quadrupole coupling constants and the asymmetry parameters are examined
      for the detection of the phase transition resulting in a significant structural
      change in the Rb(II) site. In addition, changes in the relative peak intensity
      between the Rb(I) and Rb(II) sites seem to suggest the existence of an anomalous
      intermediate phase, which is complemented by the differential scanning
      calorimetry and X-ray diffraction studies.

PMID- 11235025
TI  - Solid state NMR interaction parameters of oxygens linking titanium and silicon in
      crystalline cyclic titanodiphenylsiloxanes.
AB  - 17O static and magic angle spinning NMR spectra are reported from three
      crystalline cyclic titanodiphenylsiloxanes at magnetic fields of 5.6, 14.1, and
      17.6 T. These compounds allow the NMR parameters characteristic of Ti-O-Si
      environments to be determined. It appears from these data that the quadrupole
      interaction (C(Q)) of such environments is in the range of 3-3.5 MHz and that Si
      O-TiO3 sites are less shifted than Si-O-TiO5. The relatively large isotropic
      chemical range observed suggests that for structurally and atomically disordered
      titanosilicate-based materials the very highest applied magnetic field may not
      produce the best 17O solid state NMR spectra. There appears to be a correlation
      between the 17O shift and Ti-O bondlength.

PMID- 11235026
TI  - Experimental and theoretical 31P and 77Se nuclear magnetic shielding tensors for
      bis(dineopentoxyphosphorothioyl) diselenide.
AB  - An intergrown crystal of two phases of bis(dineopentoxyphosphorothioyl)
      diselenide 1 was investigated by goniometer 31P NMR. From the angular dependence
      of the chemical shift, the tensors of a triclinic and a monoclinic phase were
      determined. The principal values sigma11, sigma22, and sigma33, of the absolute
      nuclear magnetic shielding tensors for the triclinic phase are 134.1, 227.2, and
      375.5 ppm and for the monoclinic phase are 132.4, 227.8, and 374.2 ppm,
      respectively. In both cases, the principal axis 3 of the 31P tensor is directed
      nearly along the P=S bond and the principal axis 2 is nearly perpendicular to the
      S=P-Se plane. Calculations of the 31P and 77Se nuclear magnetic shielding tensors
      were performed for molecules of both phases of 1 and for model compounds by the
      sum-over-states density functional perturbation theory IGLO method. The rms
      distances between calculated and experimental 31P NMR icosahedral tensor values
      sigma(j) (j = 1, ..., 6) amount to 17-21 ppm. The calculated and experimental
      orientations of the 31P principal axes show a maximum difference of 5 degrees and
      rms distances of 3.2 and 3.3 degrees. For the principal value sigma33 of the
      selenium shielding tensor the agreement between calculated and experimental
      values is satisfactory, but the calculated values sigma11 and sigma22 are
      distinctly too small. Calculations for a model compound in which the methyl
      groups of the neopentoxy residue are substituted by protons lead practically to
      the same results.

PMID- 11235027
TI  - Characterization of polyalkylvinyl ether phases by solid-state and suspended
      state nuclear magnetic resonance investigations.
AB  - Pure organic polyalkvlvinyl ether phases were synthesized by suspension
      polymerization using different ratios and compositions of n-butylvinyl ether
      (C4VE) and n-octadecylvinyl ether (C18VE) with triethylene glycol divinyl ether
      or divinylbenzene as crosslinkers, respectively. These phases were investigated
      by means of solid-state 13C cross-polarization magic angle spinning nuclear
      magnetic resonance (NMR) spectroscopy and 1H high-resolution magic angle spinning
      (HR MAS) NMR spectroscopy in suspended-state. A comparison of these two methods
      showed the substantial advantages of 1H HR MAS NMR measurements. Structure
      elucidation was achieved using a 2D H,H-COSY NMR experiment performed under MAS
      conditions enabling full peak assignment of the 1H NMR spectra of these phases.
      The dynamic behavior of the polyalkylvinyl ether phases was determined by
      employing temperature-dependent measurements of spin-lattice relaxation times
      (T1) as well as accumulation of a 2D wide line separation NMR spectrum.

PMID- 11235029
TI  - Proton dynamics in letovicite, (NH4)3H(SO4)2: a 1H and 14N NMR spectroscopic
      study.
AB  - The improper ferroelastic phase letovicite (NH4)3H(SO4)2 has been studied by 1H
      MAS NMR as well as by static 14N NMR experiments in the temperature range of 296
      425 K. The 1H MAS NMR resonance from ammonium protons can be well distinguished
      from that of acidic protons. A third resonance appears just below the phase
      transition temperature which is due to the acidic protons in the paraelastic
      phase. The lowering of the second moment M2 for the ammonium protons takes place
      in the same temperature range as the formation of domain boundaries, while the
      signals of the acidic protons suffer a line narrowing in the area of Tc. The
      static 14N NMR spectra confirm the temperature of the motional changes of the
      ammonium tetrahedra. Two-dimensional 1H NOESY spectra indicate a chemical
      exchange between ammonium protons and the acidic protons of the paraphase.

PMID- 11235028
TI  - 13C NMR lineshapes of acetone adsorbed on silica.
AB  - 13C NMR data, obtained as a function of temperature with magic-angle spinning
      (MAS) and either cross polarization or direct polarization, are reported on
      acetone and a sample of acetone (an approximately equal mixture with 13C labels
      at C-1 or C-2) adsorbed on dry silica gel. Various contributions to the observed
      linewidths and T2C values are considered in terms of a previously established
      model of the acetone/SiO2 system; in that model, acetone species are in
      equilibrium between a physisorbed-acetone (non-hydrogen-bonded) state and a state
      consisting of acetone units that are hydrogen bonded to silanol moieties on the
      silica surface. Spin dynamics simulations are useful in interpreting the effects
      of variations of experimental parameters. It is concluded that the main linewidth
      contributions, which increase at lower temperatures, are: (a) a dispersion of
      chemical shifts in the hydrogen-bonded state, associated with the inhomogeneous
      character of the silica surface; (b) the interference between MAS averaging of
      the chemical shift anisotropy (especially for the carbonyl carbon) and molecular
      motion and/or chemical exchange; and (c) chemical exchange broadening. Prominence
      of the last of these contributions is most consistent with data obtained as a
      function of magnetic field strength, MAS speed, and temperature.

PMID- 11235030
TI  - New strategies for improving heart failure management: a primary care
      perspective.
AB  - Most patients with heart failure today are treated by primary care practitioners,
      not cardiologists. The Consensus Recommendations for the Management of Chronic
      Heart Failure, developed by the Advisory Council to Improve Outcomes Nationwide
      in Heart Failure, provide practice guidelines for the prevention, diagnosis, and
      treatment of heart failure. Although hemodynamic abnormalities contribute to the
      symptoms of heart failure, disease progression is attributable to neurohormonal
      abnormalities, primarily activation of the renin-angiotensin system and the
      sympathetic nervous system. Pharmacologic treatment that antagonizes these
      neurohormonal abnormalities reduces the morbidity and mortality associated with
      heart failure. Guidelines recommend that patients with systolic dysfunction and
      symptoms of fluid retention receive a diuretic followed by an angiotensin
      converting enzyme inhibitor, and, once the patient is euvolemic, a beta-blocker.
      Digoxin may be added to therapy for patients with persistent symptoms or rapid
      atrial fibrillation. Clinical trials have shown that such combination regimens
      reduce the risk of hospitalization and death in patients with heart failure.

PMID- 11235031
TI  - Predicted impact of attaining smoking reduction goals on mortality.
AB  - The impact of reducing smoking initiation, increasing smoking cessation, and
      combination approaches on life expectancy, deaths averted, and life-years gained
      in a birth cohort of 50,000 persons and in the state population (3.6 million)
      were analyzed. A 60% reduction in initiation of smoking in adolescents would
      increase life expectancy by 0.42 years. Over the next 100 years, there would be
      an additional 18,000 years of life for a birth cohort and an additional 675,000
      years of life for the state's population. The reduction in mortality, however,
      would not begin before 35 years, and only 25% of the benefit would occur in the
      next 70 years. An increase in smoking cessation would have a smaller impact that
      would occur sooner. Maximum reduction in mortality could be achieved by reducing
      initiation and increasing cessation at all ages, but a reduction in mortality
      would not occur for several decades.

PMID- 11235032
TI  - Gastritis: classification, pathology, and radiology.
AB  - Gastritis has a broad pathologic spectrum and anatomic distribution, as well as
      an evolving etiology. The Sydney pathologic classification of gastritis, which
      appeared in 1990 and was revised in 1994, emphasized the importance of combining
      etiologic, topographic, and morphologic criteria for establishing clinically
      useful diagnoses. Using this revised Sydney pathologic classification as a guide,
      we report a simpler and more practical radiologic approach to gastritis. We
      emphasize those types of gastritis that may be detected on radiologic examination
      and illustrate typical findings.

PMID- 11235033
TI  - Polycystic ovary syndrome: new perspective on an old problem.
AB  - Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of
      reproductive age. New treatment approaches resulting from a refined understanding
      of the pathophysiology are evolving. The literature shows that PCOS is an
      endocrinopathy resulting from insulin resistance and the compensatory
      hyperinsulinemia. This results in adverse effects on multiple organ systems and
      may result in alteration in serum lipids, anovulation, abnormal uterine bleeding,
      and infertility. In addition, PCOS may place the patient at long-term risk for
      the development of type 2 diabetes, hypertension, endometrial cancer, and
      cardiovascular disease. Oral contraceptives, progestins, antiandrogens, and
      ovulation induction agents remain standard therapies. However, insulin
      sensitizing agents are now being shown to be useful alone or combined with
      standard therapies. Early identification of patients at risk and prompt
      initiation of therapies, followed by long-term surveillance and management, may
      promote the patient's long-term health.

PMID- 11235034
TI  - Pokemon contagion: photosensitive epilepsy or mass psychogenic illness?
AB  - We studied a reported illness outbreak occurring on December 16, 1997, involving
      more than 12,000 Japanese children who had various signs and symptoms of illness
      after watching an episode of a popular animated cartoon, Pokemon. While
      photosensitive epilepsy was diagnosed in a minuscule fraction of those affected,
      this explanation cannot account for the breadth and pattern of the events. The
      characteristic features of the episode are consistent with the diagnosis of
      epidemic hysteria, triggered by sudden anxiety after dramatic mass media reports
      describing a relatively small number of genuine photosensitive-epilepsy seizures.
      The importance of the mass media in precipitating outbreaks of mass psychogenic
      illness is discussed.

PMID- 11235035
TI  - Trauma in the cirrhotic patient.
AB  - Cirrhotic patients requiring emergency abdominal surgery exhibit a significant
      increase in mortality. Unlike the elective surgical patient in whom there is
      often the opportunity to control ascites, improve nutritional status, and correct
      coagulation abnormalities, the trauma patient may need to undergo immediate
      emergency surgery to control bleeding or contamination. The operation may present
      significant technical difficulties in achieving hemostasis. Indicators of poor
      outcome at admission include ascites, hyperbilirubinemia, elevated prothrombin
      time, multiple injuries, and blunt abdominal trauma requiring celiotomy.

PMID- 11235036
TI  - Percutaneous dilatational tracheostomy in a community hospital setting.
AB  - BACKGROUND: Over the past 15 years, many large university hospitals have reported
      their experience with percutaneous dilatational tracheostomy (PDT). The purposes
      of this study are to evaluate the safety of PDT in a non-university hospital
      setting and to compare our results with those published in the literature.
      METHODS: The study was done by retrospective chart review. RESULTS: Over a 6-year
      period, 300 PDTs were done in two community hospitals in Tyler, Texas. There was
      one death and 12 complications. Comparison of our results and those reported in
      five recently published articles in the literature showed no significant
      difference in mortality rate, pneumothorax, bleeding, paratracheal placement,
      dislodgement, or cellulitis. There was a trend toward a significantly lower
      incidence of paratracheal placement using bronchoscopic guidance. CONCLUSION:
      Bedside PDT with bronchoscopic guidance can be safely done in a community
      hospital setting.

PMID- 11235037
TI  - Characteristics of individuals infected with the human immunodeficiency virus and
      provider interaction in the predominantly rural Southeast.
AB  - BACKGROUND: This detailed study describes the demographic characteristics,
      behavioral characteristics, care-seeking behavior, and barriers to health care
      and social services for patients infected with the human immunodeficiency virus
      (HIV) in the Southeast. METHODS: We conducted a cross-sectional study of Medicaid
      eligible HIV-positive individuals (chart abstractions [N = 679], patient surveys
      [N = 487]) and care providers (N = 101) in North Carolina. Relative risks compare
      blacks, women, and respondents reporting substance abuse with their reference
      groups. Results are compared with those of a larger sample including persons from
      Alabama and South Carolina. RESULTS: Forty-one percent of respondents did not
      receive care locally, and 69% of female respondents had young children at home.
      In the 12 months before the survey, 66% reported substance abuse; 49% reported
      multiple living situations; 11% had entered drug treatment; and 10% had
      difficulty with the law. The findings in North Carolina did not differ from those
      in Alabama and South Carolina. Mean indices from care provider surveys revealed
      low interagency knowledge and referrals. CONCLUSIONS: Patients have complex needs
      for both social services and health care. However, providers are not working
      together.

PMID- 11235038
TI  - Insulin secretion in glucose-tolerant offspring of type 2 diabetes patients in
      Trinidad, West Indies.
AB  - BACKGROUND: Genetics and environmental factors play vital roles in type 2
      diabetes. To gain insight into its pathogenesis, early study of offspring of
      affected patients is needed. METHODS: Thirty-four offspring of patients with type
      2 diabetes and 27 nondiabetic control subjects matched for sex, height, weight,
      and waist-to-hip ratio had standard oral glucose tolerance tests (75 g glucose in
      300 mL water). Homeostasis model assessment was used in measuring insulin
      resistance and sensitivity. RESULTS: Offspring had significantly higher mean
      fasting serum insulin (126.6 +/- 10.3 vs 87.5 +/- 6.9 pmol/L), incremental
      insulin at 30 to 150 minutes, and body mass index and lower insulin sensitivity
      than control subjects (49.9% +/- 3.1% vs. 71.9% +/- 5.6%), despite similar
      fasting plasma glucose concentrations. CONCLUSIONS: As in other populations, the
      offspring of Caribbean patients with type 2 diabetes are at greater risk for
      development of diabetes independent of obesity.

PMID- 11235039
TI  - Disseminated Pseudomonas aeruginosa and necrotizing pneumonia with complete
      recovery.
AB  - Pseudomonas aeruginosa pneumonia and recovery with treatment are rare in healthy
      individuals. We report the case of a 59-year-old man with P aeruginosa skin
      infection and sepsis, later giving rise to necrotizing pneumonia by hematogenous
      spread. He responded to prolonged intensive care and 3 weeks of piperacillin
      tazobactam and tobramycin therapy. There was no evidence of immunosuppression
      other than that caused by alcoholism in this unusual case. The resulting cavity
      healed completely by fibrosis in 1 year.

PMID- 11235040
TI  - Psorospermium haeckelii: a cause of pseudoparasitosis.
AB  - A 42-year-old man had nausea, vomiting, periumbilical pain, tenesmus, and
      diarrhea shortly after eating seafood. Stool microscopy showed "beaver bodies,"
      or Psorospermium haeckelii, a nonpathogenic algal organism often confused with
      enteric pathogens and commonly found in the excrement of persons consuming
      crayfish.

PMID- 11235041
TI  - Abdominoscrotal hydrocele mimicking a herniation of the bladder.
AB  - We describe an 18-month-old boy with an abdominoscrotal hydrocele that extended
      into the space of Retzius and mimicked a herniation of the bladder. Preoperative
      ultrasonography of the scrotum and lower abdomen is recommended in boys with
      suspected large hydroceles.

PMID- 11235042
TI  - Ceroid histiocytosis: an unusual cause of atraumatic splenic rupture.
AB  - A rare case of atraumatic splenic rupture due to ceroid histiocytosis is
      described in a 56-year-old man. During hospitalization, he complained of
      epigastric pain, which was not associated with nausea or vomiting. Hematologic
      indices showed steadily declining hemoglobin, and subsequent radiologic imaging
      revealed massive splenomegaly. An exploratory laparotomy revealed hemoperitoneum
      associated with a subcapsular splenic rupture. Splenic pathology showed numerous
      ceroid-containing histiocytes. We believe this to be the fourth reported case in
      the English language of atraumatic splenic rupture due to ceroid histiocytosis.

PMID- 11235043
TI  - Endocarditis due to Actinomyces viscosus.
AB  - We report a case of endocarditis caused by Actinomyces viscosus in a previously
      healthy young adult with no known identifiable portal of entry. Infective
      endocarditis caused by A viscosus is uncommon; two cases of endocarditis caused
      by this species have been previously reported. Primary actinomycotic endocarditis
      has been previously reviewed in 1993; we provide a review of additional cases
      since that report. In comparing our case with the other reported cases, we found
      that actinomycotic endocarditis (1) occurs in a wide spectrum of age, (2) affects
      primarily males, (3) has a high propensity for systemic embolization, and (4) has
      involved only native heart valves. The disease is manifested by the typical signs
      and symptoms of infective endocarditis and is curable with long-term penicillin
      therapy. The use of echocardiography in the diagnosis of endocarditis, techniques
      for improving the microbiologic diagnosis of endocarditis, and current
      indications for surgical intervention are discussed.

PMID- 11235044
TI  - Aerosolized amikacin in the treatment of Pseudomonas pneumonia in the nursing
      home setting.
AB  - Studies have shown that aerosolized aminoglycosides represent a safe and
      effective means of treating pneumonia due to Pseudomonas sp. Aerosolized
      aminoglycosides have been shown to improve clinical outcome, with less risk of
      nephrotoxicity relative to parenteral aminoglycosides. Apparently, less drug
      resistance is associated with the use of aerosolized aminoglycosides. Cost
      factors favor aerosolized delivery methods. The full recovery experienced by the
      patient in this case study suggests that aerosolized amikacin may be a safe,
      efficacious, and cost-effective means of treating pseudomonal pneumonia in
      geriatric patients. Controlled clinical trials should be conducted to further
      investigate this treatment regimen.

PMID- 11235045
TI  - Scar endometriosis manifested as a recurrent inguinal hernia.
AB  - A 24-year-old woman was initially found to have a right inguinal hernia that
      occurred suddenly after heavy lifting. A right direct inguinal hernia was found
      during the initial operative procedure. The round ligament was excised, the
      internal ring was closed, and the hernia was repaired with mesh placed on the
      floor of the inguinal canal. Four months after an uneventful postoperative
      recovery, the patient returned with pain in the right inguinal area. Over the
      next 2 months, a deep painful bulge developed. Inguinal exploration revealed an
      endometrioma rather than recurrent inguinal hernia. A portion of the original
      hernia incision included part of a previous Pfannenstiel incision made 3 years
      previously for a cesarean section. Scar endometriosis most probably occurred from
      peritoneal seeding from the Pfannenstiel incision and mimicked the findings of a
      recurrent inguinal hernia.

PMID- 11235046
TI  - Castleman's disease: atypical manifestation in an 11-year-old girl.
AB  - Castleman's disease (angiofollicular lymphoid hyperplasia) is a rare
      lymphoproliferative disorder that can be found in both nodal and extranodal
      sites. It is classified histologically as the more common hyaline vascular
      variant, a plasma cell variant, or a mixed form. The hyaline vascular variant is
      typically characterized by a benign clinical course with no constitutional
      symptoms other than localized pressure from the mass. We report an atypical case
      of the hyaline vascular variant with constitutional symptoms that have been
      clinically associated with the aggressive plasma cell variant. Diagnosis was
      confirmed histopathologically after surgical resection, which was curative and
      resulted in resolution of all symptoms. This case broadens our understanding of
      Castleman's disease as a part of the spectrum of lymphoproliferative and
      inflammatory diseases. Furthermore, it supports recent studies suggesting that
      systemic pathogenicity is related to associated cytokine dysregulation and
      highlights the need to include Castleman's disease in the differential diagnosis
      of pediatric lymphoproliferative disorders.

PMID- 11235047
TI  - Physical restraint and subcutaneous hematoma in an anticoagulated patient.
AB  - A large subcutaneous hematoma extending from the breastbone region to the left
      axillary region and left flank developed in a 86-year-old anticoagulated man
      because of repeated microtrauma from a physical restraint used to prevent his
      rising from a chair. Physicians, nurses, and physiotherapists should recognize
      that physical restraints causing pressure on the skin increase hemorrhagic risk
      in patients who take low molecular weight heparin. Accordingly, they should
      systematically check for hemorrhagic complications and attempt to limit the use
      of such devices.

PMID- 11235048
TI  - Successful use of cyclooxygenase-2 inhibitor in a patient with aspirin-induced
      asthma.
AB  - We describe the case of an aspirin-sensitive asthma patient with a history of
      anaphylactic reactions to nonsteroidal anti-inflammatory drugs. The patient was
      subsequently diagnosed with rheumatoid arthritis and treated with a
      cyclooxygenase (COX)-2 inhibitor without an adverse response. Current prescribing
      information warns to avoid using COX-2 inhibitors in aspirin-sensitive asthma
      patients. New evidence suggests that aspirin sensitivity may be linked to the COX
      1 pathway, and COX-2 inhibitors, as a result of their selectivity, may be
      beneficial in patients with aspirin-induced asthma.

PMID- 11235049
TI  - Giving young athletes a better opportunity.

PMID- 11235050
TI  - Robert Koch and the pressures of scientific research: tuberculosis and
      tuberculin.

PMID- 11235052
TI  - The medical construction of homosexuality and its relation to the law in
      nineteenth-century England.

PMID- 11235051
TI  - Scalpel or rays? Radiotherapy and the struggle for the cancer patient in pre
      second world war Germany.

PMID- 11235053
TI  - Protestant and Catholic medicine in the sixteenth century? The case of Ingolstadt
      anatomy.

PMID- 11235054
TI  - The Society of Medical Officers of Health: its history and its archive.

PMID- 11235055
TI  - The diagnosis of skeletal tuberculosis by polymerase chain reaction.
AB  - OBJECTIVE: To determine the potential of the polymerase chain reaction (PCR) for
      detecting Mycobacterium tuberculosis in skeletal samples by comparing results
      obtained by 1) Ziehl Neelsen staining, Lowenstein-Jensen and Bactec culture, 2)
      histopathology and clinical findings at the level of agreement, sensitivity and
      specificity. DESIGN: Cross sectional study. SETTING: Department of Medical
      Microbiology, Orthopaedics and Anatomical pathology, University of the Orange
      Free State Bloemfontein, South Africa. SUBJECTS: 45 consecutive patients were
      extensively investigated, 30 patients with clinical presumptive active
      tuberculosis and 15 with other pathology. RESULTS: Detection using culture could
      confirm only three of the 26 clinically diagnosed tuberculosis cases while PCR
      detection confirmed disease in 15 cases. The use of PCR increased the
      confirmation of clinically probable tuberculosis from 14 using standard
      laboratory techniques and histology to 18 of 26 cases. Calculated sensitivity and
      specificity for PCR employing culture as the "gold standard" were 100% (with 95%
      CI 29.2; 100.0) and 71.4% (55.4; 84.3), which due to low detection levels,
      basically excludes culture as a standard for statistical analysis. Sensitivity
      and specificity for PCR using histology as the "gold standard" were 78.6% (49.2;
      95.3) and 87.1% (70.2; 96.4) respectively with positive and negative predictive
      values of 73.3% (44.9; 92.2) and 90% (73.5; 97.9) respectively. Positive
      agreement between PCR and histology was 0.64 (0.4; 0.9) indicating fair
      agreement. CONCLUSION: Although numbers in the study were too low to effectively
      draw statistically valid conclusions the importance of the relevance of PCR for
      rapid detection of low numbers of acid-fast bacilli and confirmation of
      mycobacterial infection in spinal biopsies has been established.

PMID- 11235056
TI  - An outbreak of dysentery in a rural district of Zimbabwe: the role of personal
      hygiene at public gatherings.
AB  - OBJECTIVES: To characterize the nature and extent of the outbreak; to determine
      the risk factors associated with contracting shigellosis; and to institute
      disease control and preventive measures. DESIGN: Case control study. SETTING:
      Nyaure Ward, Goromonzi District, Mashonaland East Province, Zimbabwe. SUBJECTS:
      52 cases and 52 controls. A case was defined as any resident of Nyaure Ward who
      presented with bloody diarrhoea (three or more loose stools/day) between 25 July
      and 25 October 1997. MAIN OUTCOME MEASURES: Frequencies of symptoms, types of
      treatment received, risk factors for contracting the illness. RESULTS: The median
      age was 17 (Q1 = 8, Q3 = 30) years for cases and 19 (Q1 = 7, Q3 = 28) years for
      controls. Prominent symptoms were abdominal cramps (96.2%), malaise and fever
      (92.3%), nausea and vomiting (50.0%). The median duration of diarrhoea was 13 (Q1
      = 6, Q3 = 14) days. Eighteen (34.6%) cases were admitted and of these five were
      referred to a central hospital and two of them complicated with haemolytic
      uraemic syndrome. The case fatality rate was 1.6%. Twenty four(46.1%) of the
      cases had Shigella dysenteriae type I, sensitive to Nalidixic acid, Kanamycin,
      and Doxycycline but resistant to Metronidazole, isolated from the stool specimen.
      Water samples did not yield any pathogens. Significant risk factors associated
      with contracting dysentery were shared hand washing in the same standing water at
      gatherings[OR = 8.47, 95% CI: (2.43-31.33)] or within homes[OR = 60.43, 95% CI:
      (15.73 to 256.00)]. The use of Blair toilets was a protective factor[OR = 0.03,
      95% CI: (0.01 to 0.11)]. CONCLUSION: The epidemiologic evidence implicated
      contamination of water used for shared hand washing before meals as the source of
      the infection. The common practice of shared hand washing in standing water
      should be discouraged at all gatherings and within households to avoid future
      outbreaks.

PMID- 11235057
TI  - Situation analysis of obstetric care services in a rural district in Zimbabwe.
AB  - OBJECTIVE: To conduct a situation analysis of obstetric services in a rural
      district of Zimbabwe. DESIGN: Observational study. SETTING: 13 primary health
      care centres in Murewa district in Zimbabwe. MAIN OUTCOME MEASURES: Number of
      maternity beds, antenatal attendance, deliveries per month, availability of
      antenatal, intrapartum and neonatal care equipment, intrapartum monitoring and
      neonatal resuscitation skills. RESULTS: 13 of 15 primary health care clinics
      providing obstetric care in Murewa district were surveyed in 1995. Median number
      of maternity beds were nine (Q1 = 0, Q3 = 11) per clinic, median number of first
      ANC attenders per month was 15 (Q1 = 3, Q3 = 18), median number of deliveries per
      clinic per month were eight (Q1 = 0, Q3 = 16). While all clinics had laboratory
      facilities, 6/13 could estimate haemoglobin, 5/13 syphilis serology, none of the
      clinics sent blood to district hospitals for blood grouping and there were no
      microscopes at clinics for malaria parasite determination. Only 6/13 clinics used
      partographs for monitoring labour, 10/13 had suction machines for neonatal
      resuscitation while only 3/13 had ambu bags, 3/13 had oxygen and 2/13 had
      heaters. Correct methods for neonatal resuscitation were used in 3/13 clinics.
      Clean water supply, reliable power supply and the referral system were not
      optimal. CONCLUSION: Basic equipment for antenatal, intrapartum and neonatal care
      was inadequate. Essential laboratory facilities for obstetric care were lacking.
      Skills for intrapartum monitoring and neonatal resuscitation were inadequate. The
      referral system was poor. There is need for more strategic planning at primary
      health care level in this district which is known to have high perinatal and
      neonatal death rates. More emphasis should be placed on strengthening basic
      laboratory back up service for obstetric care, strengthening infrastructural and
      referral systems as well as training in areas of lost or no skills.

PMID- 11235058
TI  - The reported quality of condom use by young adult Zimbabwean males at higher
      learning centres in Harare.
AB  - OBJECTIVE: To examine the level of reported quality of condom use by young adult
      Zimbabwean males at higher learning institutions. DESIGN: A cross sectional
      descriptive survey. SETTING: Two technical colleges in Harare, Zimbabwe.
      SUBJECTS: A sample of 400 subjects (200 from each of the higher learning
      centres). MAIN OUTCOME MEASURES: Reported quality of condom use. RESULTS: All
      participants were males who had at least completed 'O' levels, or the equivalent
      of high school. The majority of the participants were single (78.2%), while a
      fifth (20.2%) were married and the remaining few were separated or living with a
      partner. Among those who were married about one fifth had children. The majority
      136 (36.8%) were Roman Catholic. The mean age of students surveyed was 24 (SD
      3.5) years. The reported quality of condom use in the last 12 months in this
      sample was measured by four items: 24.6% reported using condoms every time; 27.7%
      put the condom on every time before the penis entered the vagina for the first
      time; 29.3% still had an erection every time they withdrew from the vagina and
      26.9% held onto the condom every time they withdrew. In this study the results
      indicated that behaviour specific influences i.e. attitudes towards condom use,
      use of marijuana, the situational influences of bars, and condom self-efficacy
      were independently predictive of the reported quality of condom use. CONCLUSION:
      Using the health promotion model the results indicated that marital status,
      having been shown how to use condoms, attitudes towards condom use and use of
      marijuana were all independently predictive of the reported quality of condom
      use.

PMID- 11235059
TI  - Attendance at the Eye Department Harare, Zimbabwe: the spectrum of clinical
      presentations.
AB  - OBJECTIVE: To present data on presentation patterns of ophthalmic disease in a
      developing country, highlight areas of change and suggest policy to improve the
      current situation. DESIGN: Cross sectional study. SETTING: Sekuru Kaguvi Eye
      Department, Parirenyatwa Hospital, Harare, Zimbabwe. SUBJECTS: All new patients
      presenting to the department during a one week period. MAIN OUTCOME MEASURES:
      Referral route, time from onset of symptoms to presentation and mode of injury
      where appropriate as stated by the patient; diagnosis made by trained
      ophthalmologist. RESULTS: 196 patients presented during the five day period,
      61.2% male, 38.8% female. The majority of patients were males of working age,
      presenting themselves or referred from an urban clinic. The most common
      diagnostic group was trauma (21.9%) usually occurring in the workplace, of which
      53.5% were corneal foreign bodies. 37% of trauma cases presented the same day,
      and over 50% within 24 hours of injury. CONCLUSION: The study was carried out as
      a pilot audit project and shows there have been some noticeable changes to the
      presentation of eye disease over the last 20 years, with patients presenting
      sooner with trauma and more frequently overall. The introduction of policies
      concerning the use of safety goggles at work may begin to reduce eye disease due
      to trauma.

PMID- 11235060
TI  - Magnesium sulphate for eclampsia: putting the evidence into clinical practice.
AB  - Eclampsia is the third commonest cause of maternal mortality after haemorrhage
      and infection. The morbidity and mortality in eclampsia is related to the number
      of convulsions. The control of convulsions is, therefore, important in reducing
      maternal morbidity and mortality. Teaching hospitals in Southern Africa
      contributed to the multicentre Collaborative Eclampsia Trial, which provided the
      overwhelming evidence for the superiority of magnesium sulphate as the drug of
      choice for eclampsia. While other parts of the world have put this evidence into
      practice, this trend has not yet become uniform in Africa. This paper seeks to
      encourage African governments, teaching hospitals, the pharmaceutical industry
      and the regional Cochrane Collaboration Centre in South Africa to co-operate in
      order to facilitate the practice of evidence-based medicine in this aspect of
      maternal health in the region.

PMID- 11235061
TI  - The calcium channel blocker controversy--caveats for the practitioner and
      pharmacist.

PMID- 11235062
TI  - 'Natural' progesterone creams for postmenopausal women.
AB  - Creams containing 'natural' progesterone for application to the skin have been
      available over the counter in mainland Europe and the USA for around 20 years.
      They are not licensed in the UK and their availability here (in the form of Pro
      Gest or Pro-Juven creams, all distributed by Higher Nature) is limited to
      provision by prescription on a named-patient basis (related formulations are also
      being purchased from abroad by mail-order and via the Internet). Their UK
      distributor claims the creams can help treat menopausal symptoms and may prove
      useful in the prevention and treatment of osteoporosis in postmenopausal women.
      Here, we assess the efficacy and safety of 'natural' progesterone creams in the
      treatment of postmenopausal symptoms. In particular, we look at whether the
      products can protect against osteoporosis, or adequately oppose stimulation of
      the endometrium by exogenous oestrogen and so replace the progestogen component
      of conventional HRT.

PMID- 11235063
TI  - Managing childhood epilepsy.
AB  - An epileptic seizure is a paroxysmal, stereotyped disturbance of consciousness,
      motor function, sensation, perception, behaviour or emotion (occurring singly or
      in any combination), resulting from a cortical neuronal discharge. Epilepsy is a
      condition in which such seizures recur, usually spontaneously. Estimates suggest
      that 0.7-0.8% of school-aged children (corresponding to around 61,000 in England,
      Wales and Scotland) have active epilepsy. Here, we review the diagnosis,
      investigation and treatment of children with common forms of epilepsy.

PMID- 11235064
TI  - Why not [symbol: see text]zanamivir?
AB  - In 1999, Drug and Therapeutics Bulletin (DTB) and the National Institute for
      Clinical Excellence (NICE) concluded independently that [symbol: see
      text]zanamivir (Relenza) should not be used in managing patients with influenza.
      Recently, reviewing further evidence, NICE revised its position regarding use of
      zanamivir in 'at-risk' adults: it recommends that, under specific circumstances,
      the drug should be prescribed for patients at risk who are able start treatment
      within 48 hours of the onset of influenza-like symptoms. We disagree with this
      revised advice reasons we explain here.

PMID- 11235065
TI  - [Accreditation of the nursing service at the Varese Hospital, Italy].
AB  - The article presents the results of a project carried out by a group of four
      nurse managers of the Hospital "Ospedale di Circolo e Fondazione Macchi" in
      Varese, Italy, in order to accreditate the Nursing Service. After its
      constitution and formalization in 1994 and the definition of the goals of the
      Service, the process of continuous improvement of quality has been described. The
      accreditation process has led to the compilation of the Quality handbook. The
      Authors describe all the phases and the contents of each Manual chapter with
      explicative tables enclosed. The conclusions summarize the positive aspects at
      this point of the never ending work of continuous improvement of Quality.

PMID- 11235066
TI  - [Proposal for the criteria for accreditation for university training of nurses].

PMID- 11235067
TI  - [Relapse in the process of nursing accreditation].

PMID- 11235068
TI  - [Role of protocols and guidelines in the process of accreditation].

PMID- 11235069
TI  - [The statistical test].

PMID- 11235070
TI  - [Family dynamics: sleep quality of women caregivers of family members with
      Alzheimer disease].
AB  - This replication study/Riccio 1996) sets out to explore the Quality of sleep of
      34 women primary caregivers of Alzheimer's Disease patients at home. A
      descriptive, correlational and longitudinal design has been used. Key aspects
      considered were the quality of nocturnal sleep, the daytime sleepiness, the hours
      of caring, the educational level, the employment, the time for personal needs and
      the levels of depression and anxiety. After an initial interview, the caregivers
      were asked to fill in several instruments to measure the variables taken into
      consideration. The caregivers presented poor quality in their sleep. Quality of
      nocturnal sleep was negatively affected by more hours of caring (p < 0.02), high
      depression and anxiety levels (p < 0.05 and 0.007 respectively). The education
      level, the employment outside home and the amount of time spent for themselves,
      positively affected the quality of sleep (p < 0.01, 0.04, 0.05 respectively).
      This research pointed out that hours of caring, directly and indirectly, cause
      sleep problem to Alzheimer's Disease caregivers enhancing nursing care
      implications.

PMID- 11235071
TI  - [To fill the gap between theory and practice: a model of clinical nursing].
AB  - Despite the efforts of nursing theorists, educationalists and practitioners, the
      theory-practice gap continues to defy resolution. This paper argues that only by
      reconsidering the relation between theory and practice can the gap be closed.
      Drawing upon ideas from teaching and other practice-based disciplines, including
      nursing, the article suggests that the current model of viewing theory as
      informing and controlling practice should give way to a mutually enhancing model
      in which theory is derived from practice, and in turn influences future practice.
      This coming together of theory and practice is referred to as nursing praxis, and
      suggests that informal theory should be unique to each individual encounter with
      each patient. The clinical nurse is thus not only a practitioner, but a theorist
      and researcher, who responds to patients not according to some grand, inflexible
      theory, but by the process of reflection-in-action, drawing upon their expertise
      and a repertoire of past experiences and encounters.

PMID- 11235072
TI  - [A specialization course for clinical tutors: experience of the specialty course
      no. III at the University Campus of Biomedicine, Rome, Italy].
AB  - Clinical tutoring meant as guidance and support for the achievement of
      professional competency (which includes attitudes, knowledge, and skills) has
      proved itself as a critical opportunity for nursing students' clinical learning.
      The tutor's skill develops itself especially through the acquisition of clinical
      and psychopedagogical expertise unquestionably necessary to meet students'
      educational needs. For the third year the Universita "Campus Bio-Medico" di Roma,
      has started a Specialisation course for Clinical Tutors. The course objective is
      to achieve psychopedagogical, clinical, ethical and managerial competency.
      Although the course always maintains the same cultural, methodological, and
      managerial setting, each year it develops different key aspect linked to the
      participants' interests and educational needs. In fact, the students as active
      participants of their learning and well aware of the tutors' role, determine
      themselves such objectives. This paper is based on the principal themes of this
      year's course as they have been discussed and developed in final papers by the
      students.

PMID- 11235073
TI  - [The thesis of the university nursing diploma. Experience at the University of
      Padova, Italy].
AB  - The new didactic organization of University degree of health areas considers a
      final qualifying examination composed, among other exams, by a written
      dissertation (thesis) dealing with technical-operative-experimental matters. At
      the faculty of Medicine and Surgery of Padua University, the council of the
      Degree in Nursing proposed a document about finalities, arguments, methods and
      operative rules for the production of the thesis as an instrument for students
      and teachers. During academic year 1996/97, 49 students had been graduated, for
      the first time in Italy. About 63% of theses were highly congruent with council's
      methodological instructions. When the matter of the theses was a technical aspect
      of an assistance problem, the theses were correct from a methodological point of
      view. Many professional figures supplied support to the students for the thesis,
      giving them a complete experience of professional application. The dimension of
      the thesis suggested by the Council's instruction was unrespected, the average
      length of the theses (30.3 pages) was significantly (p < 0.01) higher than that
      proposed (20 pages). This suggests that students could have an insufficient
      synthetic capability.

PMID- 11235074
TI  - [Nurse-patient relations at hospitals in the Anzio and Nettuno communities in
      Italy].
AB  - Social surveys have been carrying out since 1983, in Sociology Course at the
      Nursing School in Nettuno, Rome. The principle aim is the professional and the
      social enrichment of the students, as well as the importance of working in group.
      These research works, passing from nursing education to a post basic nursing
      degree, belong, by now, to the nursing training. The work presented concerns
      patient-nurse relationship at the Anzio and Nettuno hospitals. The survey gave
      patients the opportunity to have a special frame where it is easier to be in good
      terms with the nurses, especially with the students, who understood the
      usefulness of the work. By this experience students realized the importance to be
      understanding person in the nursing profession.

PMID- 11235075
TI  - [Fractures of the lateral condyle of the humerus in children: results of surgical
      treatment of new and old cases].
AB  - Twenty three children with fractures of the lateral condyle of the humerus were
      analyzed. In 20 cases surgery was performed 0 to 8 days after injury. The 3
      delayed cases were operated because of one nonunion, one pseudoarthrosis, and one
      displaced union. All cases which underwent early surgical had a very good outcome
      with a follow-up observation period ranging from 8 months to 7 years. On long
      term follow-up of the delayed cases outcome was good in 2 cases. In one case with
      a 10 year history of pseudoarthrosis, the surgery resulted in a slight
      improvement. Basing on our observations, the authors believe early surgical
      intervention in indicated in order to achieve good outcomes. Delayed surgical
      treatment is justified in cases with elbow dysfunction.

PMID- 11235076
TI  - [Early results of surgical treatment of herniated nucleus pulposus in the lumbar
      spine in adults patients].
AB  - Between 1978 and 1997, 2250 patients underwent surgery due to nucleus pulposus
      herniation in the lumbar spine at the Department of Neurosurgery of the Medical
      Academy in Bialystok. Surgery was performed on 718 women (31.9% of the cases) and
      1532 men (68.1% of the cases) age ranging from 19 to 71 years. In 90.1% of cases
      herniation was found at levels L4-L5 and L5-S1. In most cases the herniated disc
      was removed following a fenestration (58.7% of the cases) or following
      hemilaminectomy of the vertebral arch (28.5% of the cases). Basing on a
      questionnaire sent out 12 months post-surgery 78.3% of the female patients and
      68.3% of the male patients evaluated the results of the above treatment as very
      good. Within the 12 months observation follow-up period, 9.9% of the analyzed
      group underwent repeated surgery.

PMID- 11235077
TI  - [Early results of short segment internal fixation of the thoracic and lumbo
      sacral spine after trauma].
AB  - The aim of this paper was to assess the results of short-segment internal
      fixation of the spine in posttraumatic instability. A group of 53 cases of spinal
      trauma was analysed using both Magerl's and Frankel's classifications. Spinal
      instability was assessed according the Sagittal Index (SI). The metaanalysis of
      the clinical material demonstrated that early decompression of the spinal cord
      and the spinal roots following trauma allows either total or partial restitution
      of their physiological functions.

PMID- 11235079
TI  - [Osteosynthesis of infected and impaired growth of the femur with vascularized
      fibular graft].
AB  - The authors present the causes of difficulties arising during treatment of
      infected non-unions. Much attention was paid to the unique character of the
      infection in the thigh and the technical problems related to it. The role of
      vascularized bone grafts was emphasised. Different possibilities of surgical
      treatment of bone loss in different localisations were presented basing on
      clinical material of 7 patients. The authors used various osteosynthesis
      techniques, most frequently external fixators. Graft healing anf remodelling with
      different kind of fixators is discussed. The frequency of graft fractures was
      stressed. The differences in the healing of graft fractures and normal fractures
      was discussed. The need of suitable elasticity of the external fixator for the
      correct healing of the transplant and its remodelling was emphasised.

PMID- 11235078
TI  - [Clinical problems related to soft tissue hemangiomas of the lower limb].
AB  - The paper presents the clinical problems related to soft tissue hemangiomas of
      the lower limbs basing on our material consisting of 19 patients, their age
      ranging from 1.5 to 53 years (average 17.4 years). Soft tissue hemangiomas were
      most commonly found in the thigh (7 cases) and in the foot (7 cases), less common
      localizations were the lower leg (4 cases) and the buttock (1 case). The most
      common symptoms were: local pain, a palpaple tumor cherry-sized to orange-sized,
      limitation of movement and joint contracture, causing limb dysfunction.
      Ultrasound and X-ray examination proved to be very useful in assessing the
      diagnosis. All patients underwent surgery with good results. The histopathologic
      examination showed 17 cases of cavernosous hemangioma, 1 case of papillary
      hemangioma and 1 case of hemangiofibroma. In the follow-up examination ranging
      from 1.5 to 23 years post-op proper limb function was found in all cases. In 2
      cases re-operations were performed.

PMID- 11235080
TI  - [Long term results of the treatment of clubfoot with postero-medial fibular
      graft].
AB  - The authors present long term results of treatment of congenital clubfoot by
      postero-medial release. Our material consisted of 82 patients, with 103 clubfeet,
      5 months to 9 years old (mean age 22 months) at the time of surgery. The age at
      the time of the final follow-up ranged from 6.3 to 27 years. Final results were
      evaluated according to the Magone classification. Basing on this classification
      we achieved very good results in 9 feet, good results in 20, sufficient results
      in 28 and poor results in 46 feet. In the analyzed group most of the results were
      either sufficient or poor--71.84% of the cases. These feet required further
      surgical procedures. The authors stress that incorrect classification for this
      type of surgery and inadequate surgical technique caused a high percentage of
      poor and sufficient results.

PMID- 11235082
TI  - [Computer stimulation of stress distribution in finite element models of the
      normal femur and after Weller, Centrament, Parhofer-Monch type prosthesis
      implantation].
AB  - The paper presents an example of application of computerized analysis in the
      evaluation of the biomechanical reactions of the bone tissue after total hip
      replacement. Finite element models of the normal femur and femurs after Weller,
      Centrament and Parchofer-Monch type hip prosthesis implantation were constructed.
      Basing on these models, a comparative analysis of the stress patterns in all
      femurs was performed according to Pauwels' method. This study showed that total
      hip replacement leads to a redistribution and diminution of stress in the bone
      tissue, because of material disconformity of the prosthesis. The authors believe
      that the evolving virtual analytic tools used in simulations will in the future
      play a major role in reconstructive surgery.

PMID- 11235081
TI  - [Shape optimization of the femoral component of hip prosthesis using the finite
      element method].
AB  - Aseptic loosening of implants in bone is the main reason of prosthesis failure.
      Stress distribution around the implant surface plays a major role in this
      process, which can be minimized by implant shape optimization. Numerical methods,
      particularly the finite element method, are an important tool in the analysis of
      stress distribution and design optimization. The paper presents the problem
      formulation for this method, illustrated by computational examples.

PMID- 11235083
TI  - [Biomechanical investigation of distraction forces appearing in the course of
      femoral lengthening in rabbits: radiological and histological study].
AB  - This study was conducted in order to determine the values of forces necessary to
      stretch bony fragments during tibia lengthening in rabbits. The aim of this study
      was to determine the conditions which lead to complications of the lengthening
      process related to the rate of distraction. The experiment was conducted on 16
      rabbits of New Zealand breed. The construction of the apparatus eliminated
      tension resulting from the so-called "bending moment". In all rabbits distraction
      was began on the 5th day after fixing the apparatus. The standard rate of
      lengthening was 2 x 0.25 mm per day. In 8 rabbits the rate of distraction was
      regulated. The distraction forces were measured and electronically recorded
      during the distraction procedure, during the animal's movement and resting
      position at strictly monitored intervals. Radiological examination of the
      lengthened tibia was performed once a week. Histological examination was
      performed in three rabbits after completion of the experiment. We made 328
      measurements of the involved distractive forces, collecting a total of 223 MB of
      data. Graphical representation of the lengthening force and it's performance
      turned out to be similar for various experimental animals and it's course was
      typical for every stage of the lengthening process. At the time of distraction of
      the apparatus the measured force increased on average by 0.87 N (minimum 0.61,
      maximum 1.1N). Abnormal rates of distraction resulted in a break of the callus
      continuity in 3 rabbits. Radiological and histological examinations were used to
      assess to confirm certain observations concerning the technique and rate of
      distraction.

PMID- 11235084
TI  - [Biological experimental models in orthopedics].
AB  - Experimental research in orthopedics is conducted on different experimental
      models. Animal models have to be characterized by high similarity and consistence
      of the animal bone tissue with human metabolism and must undergo similar
      biomechanical changes. This paper presents the advantages and disadvantages of
      the most commonly used animal models, with particular attention given to sheep.

PMID- 11235085
TI  - [Tibia reconstruction using cross-leg pedicled fibular flaps: report of two
      cases].
AB  - The paper presents the results of treatment of two children with cross-leg
      pedicle fibular flaps. A boy (10 years old) was operated because of an extensive
      defect of the proximal tibial shaft (15 cm) and soft tissue deficit due to
      osteosarcoma. He had been previously operated several times: tumor resection with
      chemiotherapy, bone reconstruction using allografts and two other procedures
      because of inflammatory complications. The second case was a 9-year old girl who
      underwent an extensive excision of congenital pseudoarthrosis of the tibia due to
      neurofibroma and reconstruction of the further fragment of the tibia.
      Vascularized fibula was nailed deep into the tibial shaft, beyond the previously
      implanted metal elements. This allowed to maintain a correct axis of the limb, a
      firm stabilization of the transplant and probably evoked a quick periosteal
      reaction of the tibia. Plaster of Paris was used to immobilize the limb.
      Postoperative course showed no complications. The flap pedicle was cut off after
      3-4 weeks. Progressive bone healing followed by bony hypertrophy was observed
      after 8 weeks. The children were able to fully load the operated extremities and
      ambulate without crutches (the boys 12 months post-surgery and the girl 6 months
      post-surgery).

PMID- 11235086
TI  - [Distraction lengthening of a hypoplastic fourth metacarpal bone: a case report].
AB  - A 17 year old female guitar player with congenital shortening of the fourth
      metacarpal in the right hand was successfully treated by distraction lengthening.
      The fourth metacarpal was lengthened by 22 mm (36%) without complications. The
      lengthening improved the function and cosmesis of the hand.

PMID- 11235087
TI  - [Melorheostosis: a case review and review of literature].
AB  - The authors present a review of the literature and the diagnostic difficulties in
      a case of melorheostosis in a 6 year old boy. Melorheostosis is characterized by
      longitudinal foci of subcutaneous sclerosis, limitation of motion in the joints
      and swelling of the knee and ankle joints. Radiologically numerous foci of
      hyperostosis similar to wax flowing down a burning candle have been noted.

PMID- 11235088
TI  - [HIV-testing of patients and operating room staff: myths and facts].
AB  - Orthopedic surgeons are at risk of acquiring HIV. Multi-center studies have
      estimated the risk of infection related with exposure to blood and other body
      fluids. New discussion concerning mandatory testing of patients who require
      invasive procedures has arisen as several reports on occupationally acquired HIV
      infections have been published. The case of the French surgeon highlighted the
      high risk of infection by blood-born pathogens related to certain surgical
      techniques. Cases of patients infected by HIV by medical personnel (by an
      American dentist and the mentioned before French surgeon) are also discussed.
      Basing on these two cases, the procedures with the highest infection risk are
      discussed, along with HIV testing policies towards surgeons of health care
      authorities in different countries. The importance of preventive measures,
      considering no cure for HIV infections is available is also stressed.

PMID- 11235089
TI  - [Report of the 3rd Polish-German symposium on orthopedic traumatology -- Krakow,
      June 1-3, 2000].

PMID- 11235090
TI  - Preliminary studies into the direct interfacing of a microreactor to a gas
      chromatographic instrument.
AB  - The paper reports on a preliminary study into the coupling of a microreactor to a
      GC-FID, using a standard GC needle as the interface between the microreactor and
      the injection port of a conventional GC. Using the injection needle as the ground
      electrode, electroosmotic flow was used to control the injection of
      reagent/sample into the GC. Photolithographic and wet etching techniques were
      used to fabricate the microreactor (channels 200 microns id, 100 microns deep) in
      a borosilicate glass substrate. The results of the effects of voltage and
      injection times on the response signal are presented. The critical obstacles to
      overcome were the backpressure posed by the carrier gas disrupting the liquid
      flow in the channels and reservoirs of the microreactor and the need to thermally
      insulate the microreactor, to prevent evaporation of solvent and reagents from
      the device.

PMID- 11235092
TI  - Microwave driven ultraviolet photo-decomposition of organophosphate species.
AB  - A novel beaker shaped electrodeless ultraviolet lamp, excited by the radiation of
      a conventional microwave oven, has been employed in the breakdown of
      organophosphate compounds in preparation for colorimetric phosphate
      determination. This new approach offers a highly rapid method of organophosphate
      decomposition prior to their analysis, with complete breakdown being achieved
      within 3 min. When evaluated using a number of inorganic and organophosphate
      compounds, quantitative release of phosphate from a carbon oxygen bond was
      achieved. Photo-oxidation of the organic triphosphate adenosine 5'-triphosphate
      results in the release of triphosphate that can then be broken down to three
      orthophosphate units by acid hydrolysis.

PMID- 11235091
TI  - An evaluation of extraction techniques for arsenic species from freeze-dried
      apple samples.
AB  - The extraction of arsenic from freeze-dried apples and subsequent determination
      of individual arsenic species by HPLC-ICP-MS is described. Solvent extraction
      with sonication using various aqueous and aqueous/solvent mixtures was initially
      evaluated by measuring total arsenic extracted by ICP-MS. A two step procedure
      using overnight treatment with alpha-amylase enzyme followed by sonication for 6
      h with 40:60 acetonitrile-water was found to provide good extraction efficiency.
      The concentration of arsenic extracted was compared with the concentration of
      total arsenic in the samples determined using ICP-MS after microwave digestion in
      order to calculate extraction efficiency. Individual arsenic species in the
      extracts were measured using HPLC-ICP-MS. The three most abundant arsenic species
      found were arsenite, arsenate and dimethylarsinic acid. Total arsenic
      concentrations in the freeze-dried apple samples ranged from 8.2 to 80.9
      micrograms kg-1 As, dry mass. By HPLC-ICP-MS, the relative amount of inorganic
      arsenic in the samples ranged from 73 to 90% of the sum of the arsenic species
      detected in each sample.

PMID- 11235094
TI  - A two-electrode configuration for simplified amperometric detection in a
      microfabricated electrophoretic separation device.
AB  - The simplified amperometric detection scheme demonstrated is based on the
      amperometric working and electrophoretic ground electrodes only. The latter
      serves as counter and pseudo-reference as well. It is shown via the successful
      determination of neurotransmitters, ascorbic acid and phenols on gold or platinum
      working electrodes that this approach is feasible for detection on a channel
      based electrophoretic separation device. Also presented is the detection of
      carbohydrates and amino acids with copper electrodes. The results were found to
      be similar to those obtained with conventional capillary systems with
      amperometric detection, albeit at much reduced analysis times.

PMID- 11235093
TI  - Determination of carbonate in marine solid samples by FTIR-ATR spectroscopy.
AB  - A method for detecting carbonate in marine solid samples (sediments, corals) by
      Fourier transform infrared spectroscopy (FTIR) coupled to the total attenuated
      reflectance (ATR) technique is described. Compared to other techniques, the
      proposed method is not based on the measurement of CO2 evolved by combustion or
      acidification of the sample, but on the direct measurement of carbonate present
      in the sample. For this reason, the method by FTIR-ATR spectroscopy does not
      require any chemical pre-treatment. The proposed method allows determination of
      carbonate in the range 6-100% (w/w) as Na2CO3 and gives comparable results with
      the determination of inorganic carbon by elemental analysis.

PMID- 11235095
TI  - Determination of morpholine in air by derivatisation with 1
      naphthylisothiocyanate and HPLC analysis.
AB  - A method for the determination of morpholine in air was developed. Samples were
      collected with adsorbent tubes containing XAD-2 resin coated with 1
      naphthylisothiocyanate (NIT). The thiourea derivative formed was subsequently
      desorbed with acetonitrile and analysed by HPLC with UV detection. The recovery
      after gas phase spiking with morpholine (2.2-1570 micrograms) was 91% (86-100%)
      with a relative standard deviation of 5.5%. No effect on recovery from relative
      humidity or amount of morpholine was seen. The lowest level tested corresponded
      to 7 mg m-3 (1/10 threshold limit value) for a 15 min sampling period with a
      sampling rate of 20 ml min-1. Exposed NIT-coated XAD-2 tubes were stable at room
      temperature for at least 2 weeks.

PMID- 11235097
TI  - Two novel procedures for automatic resolution of two-way data from coupled
      chromatography.
AB  - In order to deal with the problem of simultaneous qualitative and quantitative
      analysis of the complicated samples in analytical chemistry, two novel procedures
      for automatic resolution of two-way data from coupled chromatography were
      developed in this work. The first can be used to determine automatically the
      number of components involved in a certain peak cluster. The second method is an
      iterative resolution procedure named the stepwise key spectrum selection which
      has also been developed to resolve automatically the spectra and chromatographic
      profiles of every component in the peak cluster investigated. The results
      obtained from simulated and real data show that the proposed methods perform
      fairly well.

PMID- 11235098
TI  - Determination of free and total sulfate and phosphate in glycosaminoglycans by
      column-switching high-performance size-exclusion and ion chromatography and
      single-column ion chromatography.
AB  - Analytical procedures for the determination of free and total sulfate and
      phosphate in glycosaminoglycans by high-performance liquid chromatography were
      studied. A column-switching method coupling high-performance size-exclusion
      chromatography (HPSEC) and ion chromatography (IC) is proposed for the
      determination of free anions. Good run-to-run and day-to-day precision values
      (RSD) of < 4.7% were obtained for both anions. Total anion contents were
      determined after wet acid hydrolysis with nitric acid-hydrogen peroxide (5 + 1)
      by single-column IC and ICP-AES elemental analysis in order to validate the
      results. Recoveries ranging from 94.6 to 99.0% for sulfate and from 80.8 to 94.0%
      for phosphate were obtained. Both HPSEC-IC and single-column IC methods were
      applied to the analysis of a low molecular mass heparin, a non-fractionated
      heparin and a chondroitin 4-sulfate. From the free and total sulfate
      determinations, the content of linked sulfur was calculated and ranged from 5.1
      to 12.2% m/m.

PMID- 11235096
TI  - Multi-residue analysis of avermectins and moxidectin by ion-trap LC-MSn.
AB  - A multi-residue method was developed and validated for the quantitation and
      confirmation of avermectins and moxidectin residues in bovine liver. Target
      analytes were extracted from liver homogenate using C8 solid phase cartridges,
      chromatographed under basic pH conditions in order to promote the formation of
      analyte anions, and detected by ion-trap mass spectrometry (MS) in negative ion
      mode using an atmospheric pressure chemical ionization interface (APCI). The
      method provided detection capabilities (CC beta, where beta = 0.05) for
      eprinomectin, abamectin, doramectin, moxidectin and ivermectin of 3.1, 3.2, 2.2,
      4.0 and 3.2 ng g-1 liver respectively, well below their respective maximum
      residue limits (MRLs). The critical concentrations for MRL compliance (CC alpha,
      where alpha = 0.01) were 840, 28, 130, 130 and 130 ng g-1 respectively. Analysis
      of liver fortified at the appropriate MRLs gave recoveries (% +/- RSD) of 70.9 +/
      11.6 (n = 14), 69.1 +/- 3.9 (n = 13), 65.9 +/- 6.4 (n = 19), 69.7 +/- 9.3 (n =
      19) and 73.2 +/- 10.5 (n = 19), respectively, for each analyte. Calibration
      curves fitted a second order polynomial function (R2 > or = 0.9978) over a wide
      range of concentrations (0 to 10,000 ng ml-1). The detection of two daughter-ions
      for each analyte allowed for quantitation and the confirmation of identity. The
      method is suitable for application in European Union statutory veterinary drug
      residue surveillance programmes, since it fulfills appropriate analytical
      criteria, and has the particular advantage of enabling high throughput multi
      residue quantitation and confirmation of the target analytes.

PMID- 11235099
TI  - Enzyme-linked immunosorbent assays based on peroxidase labels and enzyme
      amplified lanthanide luminescence detection.
AB  - The enzyme-amplified lanthanide luminescence (EALL) detection is developed and
      applied for the determination of peroxidase as marker in enzyme-linked
      immunosorbent assays (ELISA). The detection scheme is based on the peroxidase
      catalysed dimerization of 4-hydroxyphenylpropionic acid (pHPPA) and the
      subsequent formation of a ternary complex with Tb(III)EDTA. Quantum yields and
      fluorescence lifetimes of the luminescent species are presented to give an
      estimate of the potential of this procedure. Two different ELISA were performed
      with the EALL detection scheme. For the first, a model ELISA for the
      determination of goat anti-rabbit IgG, a limit of determination of 3 micrograms
      dm-3 (2 fmol) of the antibody could be achieved. As second model assay, a
      commercial ELISA kit was successfully validated for the new detection scheme.
      Photometric and EALL detection were in good agreement for the determination of
      human anti-gliadin IgA in serum.

PMID- 11235100
TI  - Quantification and validation of enzyme immunoassay for urinary aflatoxin B1-N7
      guanine adduct for biological monitoring of aflatoxins.
AB  - The aflatoxin B1-N7-guanine (AFB1-N7-guanine) adduct has been established as one
      of the relevant biomarkers of dietary aflatoxin (AFB1) exposure. Measurement of
      this adduct is potentially a useful dosimeter in molecular epidemiological
      studies. This paper reports the application and evaluation of a sensitive
      indirect competitive enzyme-linked immunosorbent assay (ELISA) for the detection
      and quantification of urinary AFB1-N7-guanine adduct in high risk populations
      exposed to dietary aflatoxin. Earlier, we had reported a simple and rapid
      indirect ELISA method for AFB1-N7-guanine adduct in the urine and liver tissues
      using polyclonal antibodies specific to AFB1-N7-guanine adduct. The method was
      evaluated using a rodent model (Fischer 344), exposed to 1 mg kg-1 body mass of
      AFB1 and human urine samples obtained from a maize eating population,
      environmentally exposed to AFB1 through their diet. The levels of AFB1-N7-guanine
      adduct in rat and human urine ranged from 6.42 to 20.16 micrograms mg-1
      creatinine and from 9.30 to 13.43 ng mg-1 creatinine, respectively. The level of
      AFB1 in the diet as estimated by ELISA ranged from 1000 to 3600 ng d-1. The
      interesting observation in these studies is that the females (in both rodents and
      human subjects) are more efficient than males at excreting the adduct. Total
      adduct (DNA bound adduct and guanine adduct excreted in urine) was found to be
      similar in male and female rats. However, 63% of the total adduct was accounted
      for in urine of female rats, whereas male rats excreted 47% of the total adduct
      in their urine. The present method may find wide application as a biochemical
      tool in molecular epidemiological studies with respect to human exposure to
      dietary aflatoxins.

PMID- 11235101
TI  - Enantioselective sensor based on microgravimetric quartz crystal microbalance
      with molecularly imprinted polymer film.
AB  - We report a novel quartz crystal microbalance sensor that provides
      enantioselectivity to dansylphenylalanine enantiomers by using a molecularly
      imprinted polymer film as a recognition element. The polymeric recognition thin
      film, imprinted with chiral dansyl-L-phenylalanine, was immobilised on a gold
      electrode modified with a photoactive precursor monolayer via a self-assembly
      process using photopolymerization. The fabricated sensor was able to discriminate
      between L- and D-dansylphenylalanine enantiomers in solution owing to the
      enantioselectivity of the imprinted sites. The enantiomeric composition of L- and
      D-enantiomeric mixtures could be quantitatively determined by the fabricated
      sensor. The detection limit is 5 micrograms mL-1 with a response range of 5-500
      micrograms mL-1 at pH 10.0. The influence of the template concentration on the
      sensitivity and selectivity of the synthesised polymer membranes was investigated
      and optimised. The surface characteristics of the polymer coating were studied by
      varying the pH value of the buffer solution, and a convenient regeneration
      process was proposed to increase the reproducibility and reusability of the
      sensor by flushing with pH 2.0 buffer. The selectivity and recognition mechanism
      of the imprinted polymer film were studied with compounds that are structurally
      related to the template. The method presented in this work provides a novel means
      of preparing highly selective and sensitive chemical sensors via self-assembly
      and molecularly imprinting techniques.

PMID- 11235102
TI  - Development of a thickness shear mode acoustic sensor based on an
      electrosynthesized molecularly imprinted polymer using an underivatized amino
      acid as the template.
AB  - The preparation and characterization of electrosynthesized poly(o
      phenylenediamine) (iPoPD) as a molecular imprinting material were studied by an
      in situ quartz crystal impedance method. The changes of delta f0, delta R1, delta
      L1 and delta C0 suggest that the polymer film was compact and rigid. The
      thickness shear mode (TSM) acoustic sensor modified with this material exhibits
      molecular recognition ability to the template molecule of DL-phenylalanine. In
      the range 2-20 mM, a linear relationship between the frequency shift delta f0 and
      logC was found from the calibration graph. Scatchard analysis of the relevant
      calibration graph offers information on the equilibrium of the binding
      interaction and the recognition sites. Using this electropolymerization
      technology, the preparation of the sensor was very simple and the reproducibility
      of preparation was very good. In particular, it offers possibilities for sensor
      miniaturization.

PMID- 11235103
TI  - Molecular patterning on carbon based surfaces through photobiotin activation.
AB  - We have demonstrated the site-specific adhesion of photobiotin as a method of
      producing protein micropatterns. These patterns were created by the selective UV
      irradiation of a thin film of deposited photobiotin. The UV activated areas of
      photobiotin were then developed using fluorescently labelled avidin. The size of
      pattern produced is an order of magnitude smaller than those previously reported
      by this method. The patterns were characterised, using atomic force microscopy
      (AFM) to determine their microstructure. It was found that the AFM could
      discriminate between the areas of protein immobilised to the surface through the
      activated photobiotin, and the bare substrate surface where the inactivated
      photobiotin had been removed during the washing process. The potential of these
      patterns as sensing surfaces is demonstrated through the creation of a spatially
      patterned immunosensing surface. In this case, a biotinylated antibody was bound
      to the surface and the pattern developed using a second antibody specific to the
      immobilised biotinylated antibody. This technique could thus provide a simple and
      efficient method of producing high density immunoassay systems.

PMID- 11235104
TI  - Response surface modelling and kinetic studies for the experimental estimation of
      measurement uncertainty in derivatisation.
AB  - Response surface modelling is proposed as an approach to the estimation of
      uncertainties associated with derivatisation, and is compared with a kinetic
      study. Fatty acid methyl ester formation is used to illustrate the approach, and
      kinetic data for acid-catalysed methylation and base-catalysed
      transesterification are presented. Kinetic effects did not lead to significant
      uncertainty contributions under normal conditions for base-catalysed
      transesterification of triglycerides. Uncertainties for acid-catalysed
      methylation with BF3 approach significance, but could be reduced by extending
      reaction times from 3 to 5 min. Non-linearity is a common feature of response
      surface models for derivatisation and compromised first-order estimates of
      uncertainty; it was necessary to include higher order differential terms in the
      uncertainty estimate. Simulations were used to examine the general applicability
      of the approach and to study the effects of poor precision and of change of
      response surface model. It is concluded that reliable uncertainty estimates are
      available only when the model is statistically significant, robust,
      representative of the underlying behaviour of the system, and forms a good fit to
      the data; arbitrary models are not generally suitable for uncertainty estimation.
      Where statistically insignificant effects were included in models, they gave
      negligible uncertainty contributions.

PMID- 11235105
TI  - Determination of measurement uncertainty for the determination of triazines in
      groundwater from validation data.
AB  - Laboratories are increasingly urged to submit full uncertainties of their
      analytical results rather than only standard deviations. The determination of
      measurement uncertainties in compliance with the Guide to the Expression of
      Uncertainty in Measurement (GUM) is demonstrated using the validation approach
      explicitly endorsed by the recent edition of the EURACHEM guide for the
      determination of measurement uncertainty. Measurement uncertainty was split into
      uncertainty of the sample mass, uncertainty of the concentration of the stock
      standard solution, uncertainty of the calibration and uncertainty connected to
      within- and between-series precision. Uncertainties of sample mass and of the
      concentration of the stock standard solution were 0.26 and 1.14% for all
      analytes, which is negligible compared with the contributions of precision and
      calibration. Uncertainty of calibration was estimated from the calibration graph.
      Relative uncertainty of calibration was found to be strongly concentration
      dependent and to be the main uncertainty contribution below 0.2 microgram L-1.
      Precision was split into within-series and between-series standard deviation,
      which dominate the combined standard uncertainty at higher concentrations. The
      results obtained from these calculations are compared with results for a
      certified reference material and with the performance in an interlaboratory
      comparison. It was found that all results agreed within their uncertainty with
      the target values, showing that the estimated uncertainties are realistic.

PMID- 11235106
TI  - Development of a procedure for measuring nitrogen by cold neutron prompt gamma
      ray activation analysis.
AB  - An instrument for cold neutron prompt gamma-ray activation analysis (CNPGAA) has
      been used for the nondestructive determination of nitrogen. The samples were
      analyzed in an evacuated box to minimize background from neutron capture by
      atmospheric nitrogen. The system features lower background and lower detection
      limits than obtainable with the University of Maryland-National Institute of
      Standards and Technology (NIST) thermal neutron PGAA instrument. CNPGAA has been
      used to measure nitrogen in standard reference materials which included
      biological materials and soils; the results are in agreement with certified
      values. The detection limit for nitrogen in most biological and geological
      samples is near 1000 mg kg-1.

PMID- 11235107
TI  - Raman spectroscopy as a means for the identification of plattnerite (PbO2), of
      lead pigments and of their degradation products.
AB  - The Raman spectra of plattnerite [lead(IV) oxide, PbO2] and of the lead pigments
      red lead (Pb3O4), lead monoxide [PbO, litharge (tetragonal) and massicot
      (orthorhombic)], lead white [basic lead carbonate, 2PbCO3.Pb(OH)2] and of their
      laser-induced degradation products were recorded using a range of different
      excitation lines, spectrometer systems and experimental conditions. The
      degradation of PbO2 is more extensive along the pathway PbO2-->Pb3O4-->PbO
      (litharge)-->PbO (massicot) the shorter the wavelength of the excitation line and
      the higher its power. The Raman spectrum of PbO2, which is black and of the
      rutile structure, is particularly difficult to obtain but three bands, at 653,
      515 and 424 cm-1, were identified as arising from the b2g, a1g and e(g) modes
      respectively, by analogy with the corresponding modes of isostructural SnO2 (776,
      634 and 475 cm-1). A further oxide was identified, PbO1.55, the Raman spectrum of
      which does not correspond to that of any of the laser-induced degradation
      products of PbO2 at any of the wavelengths used. The Raman results are critical
      to the future use of Raman microscopy for the identification of lead pigments on
      artworks.

PMID- 11235108
TI  - International Measurement Evaluation Programme: IMEP-9, trace elements in water.
AB  - The International Measurement Evaluation Programme (IMEP) is an interlaboratory
      comparison scheme, founded, owned and coordinated by the Institute for Reference
      Materials and Measurements (IRMM) since 1988. IMEP-9 is the third round of trace
      elements in water evaluation following IMEP-3 and IMEP-6. Reference values for 15
      elements stating total concentrations and combined uncertainties (according to
      GUM) were established. The reference values were established mainly by isotope
      dilution mass spectrometry (IDMS) as a primary method of measurement, and values
      traceable to the SI were obtained. The four elements that could not be certified
      by IDMS were assigned values by means of other measurement techniques. Results
      from 201 laboratories from 35 countries and four continents were evaluated
      against the reference values and the comparability between the laboratories is
      presented graphically.

PMID- 11235109
TI  - Direct determination of naftopidil by non-protected fluid room temperature
      phosphorescence.
AB  - A selective and sensitive room temperature phosphorimetric method for the direct
      determination of naftopidil in biological fluids is described. The method is
      based on obtaining a phosphorescence signal from this antihypertensive drug using
      TlNO3 as a heavy atom perturber and Na2SO3 as a deoxygenator agent without a
      protective medium. This technique is named non-protected room temperature
      phosphorescence (NP-RTP), and enables us to determine analytes in complex
      matrices without the need for a tedious prior separation process. The
      optimization of Na2SO3 (8.5 x 10(-3) M) and the accurate value of pH (9.0) were
      determined using a simplex as a method of optimization. Sodium carbonate
      hydrogencarbonate buffer solution (5.0 x 10(-2) M) was used to adjust the
      suitable pH. The optimum concentration of Tl+ (8.5 x 10(-2) M) was also
      determined. The delay time, gate time and time between flashes selected were 200
      microseconds, 200 microseconds and 5 ms, respectively. Under the above conditions
      we propose a method to determine naftopidil by direct measurement of
      phosphorescence intensity with an emission wavelength of 526 nm and an excitation
      wavelength of 296 nm in the concentration range 0.05-1.00 mg L-1. Under these
      conditions the phosphorescence signal appears in 3 min once the sample has been
      prepared. Optimization of the various conditions permitted the establishment of
      an NP-RTP method for the determination with a detection limit, according to the
      error propagation theory, of 21.0 ng mL-1. The repeatability was studied using 10
      solutions of 0.20 mg L-1 of naftopidil; if error propagation is assumed, the
      relative error is 1.39%. The standard deviation for replicate samples was 1.1 x
      10(-2) mg L-1. This method was successfully applied to the determination of
      naftopidil, in human urine with recoveries between 106 and 112%.

PMID- 11235110
TI  - Separation and preconcentration of MnVII/MnII speciation on crosslinked chitosan
      and determination by flame atomic absorption spectrometry.
AB  - A novel method for the separation and preconcentration of MnVII/MnII with
      crosslinked chitosan (CCTS) and determination by flame atomic absorption
      spectrometry (FAAS) has been developed. The adsorption rate of CCTS for MnVII was
      98% at pH 3, while MnII was not adsorbed. MnVII was eluted from the CCTS with 10%
      (m/v) oxammonium hydrochloride and determined by FAAS. MnII was determined from
      the total manganese present after MnII in the water samples was transformed into
      MnVII. The detection limit (3 sigma, n = 10) for MnVII was 1.98 micrograms l-1
      and the relative standard deviation less than 6.6% at the 10 micrograms l-1
      level. The method was applied to environmental water samples with recoveries of
      between 95-103%.

PMID- 11235111
TI  - A rapid method for peroxide value determination in edible oils based on flow
      analysis with Fourier transform infrared spectroscopic detection.
AB  - The development of an automated, rapid and highly precise method for
      determination of the peroxide value in edible oils based on a continuous flow
      system and Fourier transform infrared (FTIR) spectroscopic detection is
      described. The sample stream was mixed with a solvent mixture consisting of 25%
      (v/v) toluene in hexanol which contained triphenylphosphine (TPP). The
      hydroperoxides present in the sample reacted stoichiometrically with TPP to give
      triphenylphosphine oxide (TPPO) which has a characteristic and intense absorption
      band at 542 cm-1. A 10% (m/v) TPP solution in the solvent mixture and a 100 cm
      reaction coil were necessary for complete reaction. FTIR transmission spectra
      were recorded using a flow cell equipped with CsI windows having an optical
      pathlength of 100 microns. By using tert-butyl hydroperoxide spiked oil standards
      and evaluation of the band formed at 542 cm-1 a linear calibration graph covering
      the range 1-100 PV (peroxide value; mequiv O2 kg-1 oil) was obtained. The
      relative standard deviation was 0.23% (n = 11) and the throughput 24 samples h-1.
      The developed system was also applied to the determination of PV in olive,
      sunflower and corn oils, showing good agreement with the official reference
      method of the European Community which is based on titration using organic
      solvents. The results obtained clearly show that the developed method is superior
      to the standard wet chemical method, hence suggesting its application in routine
      analysis and quality control.

PMID- 11235113
TI  - Simultaneous (or sequential) determination of the total polyphenol index (or
      I280) and density in wines by flow injection.
AB  - Flow injection methods for the determination of the total polyphenol index, the
      'index 280' (I280) and dissolved solids in wines are proposed. The determination
      of the total polyphenol index is based on the Folin-Ciocalteu reaction in a basic
      medium and subsequent spectrophotometric detection at 750 nm. The direct
      measurement at 280 nm of the wine allows the determination of I280 with a simple
      manifold. The dissolved solids determination is based on the displacement of a
      light beam when the refractive index of the medium changes. This phenomenon,
      followed by a change in the absorbance in a photometric detector, usually takes
      place when an injected sample reaches the flow cell, and it is magnified on
      passage of the light beam in the radial direction instead of the more common
      axial direction. The use of a capillary (4 cm x 1.1 mm id) as the flow cell
      allows monitoring of the injected plug. A simple manifold coupled with a diode
      array spectrophotometer allows the determination of these parameters with a
      frequency of at least 90 h-1. Depending of the method adopted for the
      determination of polyphenols, Folin-Ciocalteu or I280, either a manifold
      different from that used for determining dissolved solids or the same,
      respectively, is required. The methods have been successfully applied to
      different wines and were substantiated well with official methods.

PMID- 11235112
TI  - Flow injection manifold for the direct spectrophotometric determination of
      bismuth in pharmaceutical products using Methylthymol Blue as a chromogenic
      reagent.
AB  - A new simple and rapid flow injection method is reported for the direct
      determination of bismuth in pharmaceutical products. Methylthymol Blue (MTB) was
      used as a chromogenic reagent and the absorbance of the colored Bi(III)-MTB
      complex produced was monitored at 548 nm. The various chemical and physical
      variables were optimized and a study of interfering ions was also carried out.
      Linear calibration graphs were obtained from 0 to 100 mg l-1 Bi(m) (120
      injections per hour). The precision was very good (sr = 1.3%) and the limit of
      detection was cL = 0.150 mg l-1. The average accuracy was also very good (er =
      0.75%) and was evaluated by comparison of the results obtained with those claimed
      by the manufacturers. The method was found to be adequately selective,
      considering the ions that the samples contain.

PMID- 11235114
TI  - Measurement of near zero concentration: recording and reporting results that fall
      close to or below the detection limit.
AB  - Issues relating to the recording and reporting of analytical data obtained where
      the concentration of analyte is around or below the detection limit are
      discussed. The following recommendations are proposed. Analytical results should
      be recorded by the analyst exactly as they occur, including any negative results,
      and such records retained for an appropriate length of time. For the purposes of
      quality assurance in the laboratory (including method validation, internal
      quality control, and proficiency testing), negative results should be used as
      they stand. Analytical results reported to a customer should be accompanied by a
      statement of uncertainty including, in the present context, uncertainty at low
      concentrations of analyte. The method of editing of reported results must be a
      contractual matter between the analyst and the customer, but a statement of the
      procedure used should accompany the results and should be explicit. Normally such
      editing should be restricted to setting negative results to zero. The customer
      should be encouraged to pass on the statement to all end users. Data intended for
      the public domain should be accompanied by a statement detailing the uncertainty,
      the method of editing, and the location of the unedited data. Most types of
      statistical processing of datasets containing low concentrations of analyte
      should be undertaken on the unedited data.

PMID- 11235115
TI  - Process NMR spectrometry.

PMID- 11235116
TI  - Heads up on osteoporosis.

PMID- 11235117
TI  - The hypertension initiative of South Carolina. Promoting cardiovascular health
      through better blood pressure control.

PMID- 11235118
TI  - Early exposure to primary patient care in the first year medical school
      curriculum.

PMID- 11235119
TI  - Response to complementary and alternative medicine among family medicine and
      other primary care physicians in South Carolina.

PMID- 11235120
TI  - Principles of medical ethics: the proposed revision of 2001.

PMID- 11235121
TI  - Complementary medicine: the alternative alternative?

PMID- 11235122
TI  - [An empirical research for demand of influenza vaccination].
AB  - PURPOSE: This article examines the demand for influenza vaccination in Japan.
      METHODS: Original date were obtained from a survey conducted by the authors. Two
      approaches, usual demand analysis and conjoint analysis, were employed. The
      second approach, conjoint analysis, uses people's statements on how they would
      respond to different hypothetical situations. In this research, we ask people
      whether they wish to be vaccinated given different circumstances such as costs of
      vaccination, degree of convenience, and outbreak news. RESULTS: In the demand
      analysis, the vaccination rate during the 1999-2000 season was found to have
      increased by 0.8 percentage points compared to that of the previous season. The
      rate increased by 1.0 to 3.5 percentage points among the group of people who
      experienced influenza in the previous season. The vaccination rate also increased
      by 31-47 percentage points for those who were vaccinated in the previous season.
      A 10 percentage increase in household income decreased the demand for vaccination
      by 2 percentage points. Although household income was significant in only with
      the largest sample, this result may indicate that the time or opportunity cost
      for vaccination decreases the vaccination demand. In the conjoint analysis, the
      financial cost was significantly negative. When the cost was reduced from the
      current level of 6,000 yen to free of charge, the vaccination rate would increase
      by 43.5 percentage points. Were vaccination available at night or during
      holidays,! or at school or work, the rate would increase by 11 percentage points,
      or 16 percentage points, respectively. Most of all, news of influenza prevalence
      was very influential in increasing the desire for vaccination by 33 percentage
      points. Vaccination experience and last year's influenza experience were both
      significantly positive, increasing the rate by 22 and 8 percentage points,
      respectively. CONCLUSIONS: In the demand analysis, influenza experience and
      history of vaccination during the 1999-2000 season were found to be influential
      regarding the decision for vaccination. From the conjoint analysis, providing
      vaccination of night or during holidays, as well as at work or at schools would
      increase the demand. News of influenza outbreaks were also found to increase the
      vaccination demand. Higher income, however, was found to have a negative
      influence, suggesting that opportunity costs may be an important factor for some
      individuals. Habit formation effects through a history of vaccination plays quite
      an important role in vaccination demand.

PMID- 11235123
TI  - [A system of health education using dietary assessment].
AB  - We decided to focus attention on healthy young people, and to conduct a survey of
      their diet, as well as their physical activity and health condition, so that we
      made diagnoses and also give instructions on each subject using a computer
      program to promote their health. We carried out this experiment using this method
      with 836 young female subjects in order to find out whether it can be applied as
      a useful health education approach. 1. According to the survey, when the subjects
      made efforts in making the instructions as convenient as possible, the percentage
      of subjects who could carry out advice even 4 months later was seen to be higher.
      2. The advice for which a significantly high percentage of subjects said "want to
      improve their daily action" and could actually carry out and improve them, was as
      follows: they should eat vegetables, have a substantial breakfast, drink milk
      every day, refrain from too much salt, not go without meals, increase the
      frequency of eating seaweed, and refrain from snacks. 3. The two kinds of scores
      used to evaluate diets showed that assessment after nine months gave lower values
      than those obtained when this survey started. Using these two evaluating scores,
      changes in diets were divided into five patterns, and their relation to the
      question "whether they used the advice or not" was examined. As a result, the
      percentage showing favorable diet changes in subjects who "took advice" was
      showed to be significantly high. 4. Subjects who received advice on physical
      activity exhibited improvement in carrying out routine exercises as well as
      making their daily life more active. 5. With subjects who took advice on both
      diet and physical activity, the number who complained about fatigue was
      significantly reduced. Although it is difficult to improve diet and exercise
      habits, the results of the survey suggest that our approach should be useful for
      improving health.

PMID- 11235124
TI  - [The effects of a health promotion program on physical, mental, and dietetic
      health status in climacteric women].
AB  - PURPOSES: The purpose of this study was to evaluate the effects of a six months
      health promotion program on physical and mental health status assessments in
      climacteric women. METHODS: Seventy-two women, with a mean (+/- SD) age of 51.3
      (+/- 3.1 yr.), body weight of 51.5 (+/- 6.3 kg), and Body Mass Index of 22.4 (+/-
      2.4 kg/m2), residing in Tokyo Metropolitan area, participated as subjects in a
      health promotion program, completing health status assessments. Health promotion
      was performed once a week, two hours per session, sixteen times. The lecture and
      exercise program, in the first half, included basic information on diet, exercise
      and relaxation, and prevention of life-style related disease, and instructions
      for walking exercise, dancing, and dumbbell exercise. In the latter half, they
      performed extended walking, stretching, and autogenic training for relaxation.
      Healthy foods were also supplied. Before and after the program, health status was
      assessed, with a general medical health check, a questionnaire regarding
      nutrition, exercise and relaxation activities, and determination of dietary
      intake based on food records, eating behavior, complaints (CMI, Nichidai stress
      score) and physical activity levels. RESULTS: After the six months of the
      program: 1) Total cholesterol levels had decreased significantly, along with both
      systolic and diastolic blood pressure, body weight and BMI; 2) Major nutrient
      intake, density of nutrients and eating behavior were improved, with decrease in
      daily salt intake, and increase significant in daily energy expenditure; 3)
      Stress scores by the Nichidai stress check were decreased significantly, subjects
      with higher stress scores at the beginning of programs having marked change, and
      neurotic tendencies were decreased in CMI categories II-IV. CONCLUSION: These
      results suggest that, in order to maintain and/or improve the QOL of climacteric
      women, good dietary habits and physical activities, such as walking, and
      psychological support are essential. Further long-term investigations of larger
      populations (middle-aged to elderly) are now necessary.

PMID- 11235125
TI  - [A changing pattern of food frequency according to aging. A study in a rural
      cohort with 14-year follow-up].

PMID- 11235126
TI  - [Relationship between keeping a companion animal and instrumental activity of
      daily living (IADL). A study of Japanese elderly living at home in Satomi
      Village].
AB  - OBJECTIVE: The purpose of this study was to clarify the relationship between the
      companionship of an animal and the level of Instrumental Activity of Daily Living
      (IADL) of elderly people living at home, and to consequently determine beneficial
      effects on the overall health of the elderly. METHODS: For this study, 400
      elderly people aged 65 years and over were randomly selected from among the 1,345
      citizens of Satomi Village, Ibaraki Prefecture. Self-administered questionnaires
      were mailed to the selected subjects in March of 1999. In the survey, the
      respondents were asked if they could accomplish all seven IADL activities.
      Subjects for whom this was the case were classified as having no IADL disability.
      Elderly who answered "No" for even one were listed as having an IADL disability.
      Using the existence of an IADL disability as a dependent variable and various
      factors related to companion animals as independent variables, a logistic
      regression analysis was performed. RESULTS: Out of the 400 individuals, 84.8%
      responded. With respect to the possession of a companion animal, the number of
      participants who never had a companion animal was 115 (35.8%); while 118 (36.8%)
      possessed a companion animal in the present. With regard to factors relevant to
      IADL of elderly people, the odds ratio (OR) adjusted for age and sex for
      participants who owned dogs was 0.53 (95% confidence interval [CI] 0.27-0.99)
      relative to those who never had a companion animal: The difference was
      significant. For those respondents who indicated that their companion animals
      were their best friends, the OR was 0.48 (95% CI 0.23-0.99), and again
      significant. The OR tended to decrease with increase in the duration of owning a
      companion animal. CONCLUSION: In this study, owning a dog and everyday contact
      with the companion animal were related to the IADL of the elderly living at home.
      It is possible that keeping a companion animal may be linked to better overall
      health in the elderly.

PMID- 11235127
TI  - [Utilization of emergency ambulances in Yokohoma City, Japan].
AB  - OBJECTIVE: In recent years, the annual number of emergency ambulance (EA) calls
      has increased in Yokohama city, Japan. A questionnaire study was carried out to
      describe behavioral features of the users in Yokohama city, and to investigate
      their relationship with the increase in EA utilization. METHODS: We randomly
      recruited 2,910 citizens, aged 15 years or older, for the questionnaire study and
      a total of 2,294 (78.8%) replied. The questionnaire included questions about
      their demographic characteristics, history of EA use, existence of family
      doctors, and knowledge of emergency medical services and emergency medical
      information centers. Additionally, respondents who had used EA previously were
      asked about their reasons for this. RESULTS: A total of 513 (22.4%) respondents
      answered that they had used EA previously. A slightly higher rate of EA use was
      shown among elderly people, 65 years old or over (a rate of 26.2%). The major
      reason for requesting EA use was the urgency of the disease or the injury
      (61.8%). 182 respondents answered that they requested EA as a means of
      transportation. However, most of them also mentioned that the urgency of the
      disease or the injury was one of the reasons for their request. This survey
      showed no evidence that the citizens of Yokohama have used EA improperly. Elderly
      people, among whom the annual number of EA uses has increased rapidly over the
      years, tended to employ EA in a way more in line with regulations than other
      generations. CONCLUSION: This study suggested that the basic reason for the
      increase of EA utilization in Yokohama city was not due to inappropriate demand
      but to the aging of the population.

PMID- 11235128
TI  - [Critical pathway for the treatment of acute myelogenous leukemia].
AB  - Based on analysis of data from 10 patients newly diagnosed as having acute
      myelogenous leukemia (AML), we developed a critical pathway (CP) to prevent
      infection and thus shorten the period of hospitalization. This CP shows
      laboratory test results, vital signs, chemotherapy regimen, concomitant
      supportive care and oral medications, gargling with antiseptic mouthwash, other
      anti-infection measures, diet, room conditions, patient education in anti
      infection measures, outcome, and variance on the vertical axis and time on the
      horizontal axis. After introduction of the CP, 9 of the newly diagnosed AML
      patients did not experience severe treatment-related complications during a mean
      hospitalization of 29 days until remission and 95 days until discharge. These
      results suggest that the present CP makes it possible to shorten the hospital
      stay, reduce treatment costs, and improve the quality of life of AML patients.

PMID- 11235129
TI  - [Outcome of acute myelogenous leukemia in 41 patients treated with idarubicin:
      the prognosis of t(8;21) cases].
AB  - Idarubicin (IDR) has been used as the main drug in induction chemotherapy for
      acute myelogenous leukemia (AML) in the USA and Europe. Between May 1995 and
      October 1998, we treated 41 cases of fresh AML using IDR induction chemotherapy
      and analyzed the clinical course, remission rate, relapse rate and prognosis. The
      results obtained in these cases were similar to those in 26 cases treated with
      daunorubicin (DNR) in our hospital according to JALSG-AML92. The outcome in cases
      with abnormal chromosomes and cases showing relapse was very poor. In particular,
      all 5 t(8;21) cases in our series relapsed, suggesting that t(8;21) cannot be
      considered a favorable prognostic factor in cases treated with IDR-containing
      regimens. However, 3 of the 5 t(8;21) cases were positive for CD56, which itself
      is an unfavorable prognostic factor. Thus it is possible that CD56 was related to
      the poor outcome. Intensive post-remission induction chemotherapies will be
      required in order to obtain prolonged disease-free survival.

PMID- 11235130
TI  - [Systemic inflammatory response syndrome triggered by necrotizing cholecystitis
      after treatment of underlying low titer cold agglutinin disease].
AB  - In April 1996, a 77-year-old man initially presented with fever, rash and
      polyarthralgia, and was diagnosed as having low titer cold agglutinin disease
      with acute hemolytic anemia. The patient's condition and laboratory findings
      improved after administration of corticosteroid (prednisolone 60 mg). In June
      1996, however, he developed acute cholecystitis and died due to sepsis,
      disseminated intravascular coagulation and multiple organ failure. During the
      course, the levels of inflammatory cytokines such as TNF-alpha and IL-6 were
      correlated with the pathology, and the disease was diagnosed as systemic
      inflammatory response syndrome (SIRS). Autopsy revealed necrotizing
      cholecystitis, erythrophagocytosis in the liver, and cytomegalovirus infection in
      the lung and gall bladder. This was considered to be a rare case of low titer
      cold agglutinin disease complicated by SIRS.

PMID- 11235131
TI  - [Effective use of camostat mesilate for chronic disseminated intravascular
      coagulation complicated by thoracoabdominal aortic aneurysm].
AB  - A 73-year-old man who had been receiving treatment for hypertension and angina
      pectoris was admitted to hospital following a transient ischemic attack. He was
      diagnosed as having chronic disseminated intravascular coagulation (DIC)
      complicated by a thoracoabdominal aortic aneurysm, and was treated with heparin
      sodium and a protease inhibitor. Although the DIC was controlled, the patient had
      to remain hospitalized in order to receive the medication by continuous infusion.
      Therefore, the heparin sodium and protease inhibitor were replaced by camostat
      mesilate, a drug suitable for oral administration and widely used for treatment
      of chronic pancreatitis. The drug proved effective for the chronic DIC, thus
      allowing the patient to receive regular treatment on an outpatient basis, and
      improving his quality of life.

PMID- 11235132
TI  - [Two cases of B cell lymphoma associated with hemophagocytic syndrome].
AB  - B cell lymphoma-associated hemophagocytic syndrome (B-LAHS) is clinically
      characterized by hepatosplenomegaly and bone marrow invasion without
      lymphadenopathy and skin lesions. Several cases of B-LAHS have been reported to
      demonstrate histopathologic findings of intravascular lymphomatosis (IVL), which
      in Western countries is characterized by a high rate of skin involvement and,
      rarely, bone marrow involvement and hemophagocytosis. Here we describe two
      interesting cases of B-LAHS. One patient was a 52-year-old woman whose bone
      marrow showed proliferation of large CD20-positive cells and hemophagocytosis at
      presentation. Combination chemotherapy was not effective, and the patient died of
      progressive disease. At autopsy, the lymphoma cells showed extravascular
      proliferation in many organs such as the bone marrow and liver, whereas in the
      adrenal glands, the lymphoma cells showed intravascular proliferation. The other
      patient was a 50-year-old man who had swellings of the bilateral kidneys and
      adrenal glands at presentation. Skin involvement by large lymphoma cells, a rare
      complication of B-LAHS, was observed. At autopsy, there was no evidence of IVL.
      Both of these patients showed high fever and cytopenia, and the disease took an
      aggressive clinical course, as in other reported cases of B-LAHS.

PMID- 11235133
TI  - [Primary renal non-Hodgkin's lymphoma presenting as immune thrombocytopenia].
AB  - A 25-year-old man was admitted to our hospital because of hematuria, anemia and
      thrombocytopenia. Laboratory examinations revealed an increased number of bone
      marrow megakaryocytes and an increased level of platelet-associated
      immunoglobulin G, suggesting immune thrombocytopenia. Computed tomography of the
      abdomen showed enlargement of the bilateral kidneys with multiple low-density
      areas, although neither lymphadenopathy nor hepatosplenomegaly was evident. After
      amelioration of the thrombocytopenia by prednisolone therapy, open renal biopsy
      was performed and a diagnosis of diffuse large B-cell non-Hodgkin's lymphoma was
      made. The patient achieved complete remission after CHOP therapy. This was
      thought to be a rare case of primary renal non-Hodgkin's lymphoma initially
      presenting as immune thrombocytopenia, which was treated successfully by
      chemotherapy.

PMID- 11235134
TI  - [T-cell prolymphocytic leukemia complicated by diffuse large B-cell lymphoma of
      the stomach].
AB  - We describe a case of T-cell prolymphocytic leukemia (T-PLL) in a 76-year-old
      man, who developed diffuse large B-cell lymphoma (DLBL) of the stomach, a
      previously unreported occurrence. The patient was referred to our hospital
      because of marked leukocytosis (40,000/microliter) without clinical symptoms. He
      was diagnosed as having T-PLL on the basis of the characteristic cell morphology
      and immunophenotype (CD2+, CD3+, CD4+, CD5+, CD7+, CD8-, CD25-, TCR alpha/beta+),
      but cytogenetic analysis showed no abnormalities. Fifteen months later, he
      developed a gastric tumor. Biopsy of the tumor revealed DLBL without features of
      MALT lymphoma; Helicobacter pylori was not detected. Chemotherapy eradicated the
      tumor, whereas the T-PLL was resistant to the therapy. The disease showed an
      indolent course for about 2 years thereafter. Immunological derangement due to T
      PLL might have potentiated the development of DLBL in this case.

PMID- 11235135
TI  - [Mixed-type autoimmune hemolytic anemia after splenectomy for idiopathic
      thrombocytopenic purpura].
AB  - A 30-year-old woman was admitted because of anemia and jaundice in 1999. She had
      been diagnosed as having idiopathic thrombocytopenic purpura (ITP) in 1996, but
      had shown no response to prednisolone (PSL). Subsequent splenectomy in 1998,
      followed by further treatment with PSL, had also been ineffective. On admission
      in 1999, the direct and indirect Coombs tests gave positive results, the cold
      agglutinin titer was high with anti-I specificity (IgM), and warm-type
      autoantibody (IgG) was positive. Autoagglutination of the patient's red blood
      cells was 3+ at 37 degrees C. A diagnosis of mixed-type autoimmune hemolytic
      anemia (AIHA) associated with ITP was made. Mixed-type AIHA occurring after
      splenectomy for ITP is very rare, only one case having been reported to date.

PMID- 11235136
TI  - [Childhood t(8;21) acute myelocytic leukemia: a comparison of clinical features
      and risk factors with adult cases].
AB  - Despite the abundance of reports describing adult cases of t(8;21) acute
      myelocytic leukemia (AML), childhood cases have received little attention. We
      retrospectively investigated 14 childhood cases of t(8;21) AML, and compared
      their clinical characteristics with those of adult cases, focusing on the risk
      factors for poor prognosis. Seventy-one percent of the patients had fever. Their
      mean leukocyte count was 12,700/microliter, and they showed decreased NAP
      activity. The cell surface showed positivity for CD13, 33, 19, 34, and HLA-DR.
      The complete remission rate was 100%, and relapse was observed in three of the
      patients. Bone marrow eosinophilia was present in a smaller proportion of the
      childhood cases than in the adult cases. Although an increased leukocyte count,
      tumor formation, and other risk factors have been reported in adults, there was
      no correlation between these factors and prognosis in our childhood cases. As
      children who showed AML relapse had TdT-positive blasts, detectable blast TdT
      activity may be a risk factor for relapse in childhood cases of t(8;21) AML.
      However, to confirm this, a study with a larger subject base should be conducted.

PMID- 11235137
TI  - [The usefulness of urinary FDP in the diagnosis of bladder cancer: comparison
      with NMP22, BTA and cytology].
AB  - PURPOSE: We assessed the utility of urine fibrin/fibrinogen degradation products
      (FDP) as the screening test for bladder cancer. MATERIALS AND METHODS: Single
      voided specimens were obtained from 87 consecutive patients (61 men and 26 women,
      mean age 70.7) on cystoscopy, and FDP, NMP22, BTA and cytology test were
      performed for the same specimens. Final diagnosis of bladder cancer was made by
      histological examination, which were compared with the results of above four
      screening methods. RESULTS: Histologically confirmed bladder cancer was found in
      14 cases. Overall sensitivity of urinary FDP, NMP22, BTA and cytology were 79,
      64, 36 and 36%, respectively. While the sensitivity of FDP was significantly
      higher than that of BTA and cytology, no significant difference was found between
      FDP and NMP22. Overall specificity of these four methods were 69, 78, 92 and 90%,
      respectively. The specificity of FDP and NMP22 were significantly lower than that
      of BTA and cytology, but satisfactory as a screening test. The sensitivity of the
      four methods for low-grade and non-invasive tumors were 70, 50, 30 and 10% (G1 or
      G2, n = 10), and 75, 58, 33 and 25% (Ta or T1, n = 12), respectively. FDP might
      have a high sensitivity for even low-grade and non-invasive tumors. CONCLUSIONS:
      FDP in voided urine is a good screening method for bladder cancer because of its
      high sensitivity for low-grade and non-invasive tumors, and its diagnostic
      ability could be superior to NMP22.

PMID- 11235138
TI  - [A study on the mechanism of the spermatogenic damage after vasectomy in rats].
AB  - PURPOSE: Vasectomy may result in damage to spermatogenesis. There are several
      explanations for this damage, including an increase of pressure in the
      seminiferous tubules and an autoimmune reaction. Recently, vasectomy has been
      reported to induce germ cell death by apoptosis. However, the exact mechanism of
      this vasectomy-induced germ cell apoptosis is unclear. To elucidate this
      mechanism, we designed a vasectomized rat model and examined the testiscular
      alterations and apoptotic degeneration biochemically and
      microhistopathologically. Particularly, we analyzed the expression of nitric
      oxide synthase (NOS) and nuclear factor kappa B (NF kappa B), which plays a
      critical role in the induction of the iNOS gene, in the testis after vasectomy to
      gain insight into the association between germ cell apoptosis and these factors.
      MATERIALS AND METHODS: The testes of 40 Wistar rats (10-weeks old) were studied
      at 1, 2, 5 and 10 weeks after unilateral (left) vasectomy. Wistar rats weighting
      290 to 310 g were divided into 2 groups and subjected to underwent either
      unilateral vasectomy or sham surgery under ether anesthesia. Bilateral testes
      were carefully observed biochemically and histopathologically. Apoptosis was
      detected by an in situ end-labeling technique (detection of cellular DNA
      fragmentation) and electron microscopy. Neuronal NOS (nNOS), endothelial NOS
      (eNOS) and inducible NOS (iNOS) protein was detected by Western blotting and
      immunohistochemical studies using each NOS monoclonal antibody. To confirm the co
      localization of cellular DNA fragmentation in germ cells and each NOS, each set
      of consecutive testis sections (one stained for cellular DNA fragmentation and
      the others for each NOS) were examined. Expression of NF kappa B proteins was
      examined immunohistochemically using a NF kappa B p65 polyclonal antibody.
      RESULTS: At 5 and 10 weeks after vasectomy, the vasectomized left testis was
      significantly lighter than the unvasectomized right testis and sham-operated
      testis. At that time, the seminiferous tubules of vasectomized testes were highly
      damaged, presenting narrow tubular diameter, disorder of cellular arrangement,
      depletion of the germ cells, and local interstitial fibrosis. Vasectomized testes
      demonstrated a significantly increased number of apoptotic germ cells per cross
      sectional area compared with sham-operated testes at 5 and 10 weeks after
      operation (p < 0.01). Electron microscopy revealed apoptotic germ cells each with
      a darkly stained nucleus. Western blotting and immunohistochemical studies
      demonstrated that iNOS proteins were more strongly expressed on vasectomized
      testes as time passed after vasectomy. Examination of consecutive sections from
      the vasectomized testis revealed that visibly apoptotic germ cells that exhibited
      positive staining for cellular DNA fragmentation were also intensely stained for
      eNOS and iNOS. NF kappa B p65 proteins were more strongly expressed in the
      nucleus of germ cells in the vasectomized testis than in the sham-operated
      testis. CONCLUSIONS: We found that vasectomy results in damage to spermatogenesis
      in adult rats, that may induce germ cell apoptosis, and that iNOS and NF kappa B
      may play a critical role in the germ cell apoptosis after vasectomy.

PMID- 11235139
TI  - [The significance of early detection for prostate cancer in mass screening].
AB  - PURPOSE: In Mitaka city, mass screening for prostate cancer was conducted for 3
      years from 1995 to 1997. Clinical stages were compared between patients found by
      screening and those diagnosed at our clinic during the same time. The
      significance of serum-free prostate specific antigen (PSA) in mass screening for
      prostate cancer was examined. MATERIAL AND METHODS: A prospective clinical trial
      was conducted on men aged 50 years or older. The primary examination consisted of
      taking the international prostate symptom score, quality of life score, PSA
      (Tandem-R) and digital rectal examination (DRE). If PSA was greater than 4.0
      ng./ml and/or if DRE suggested cancer, transrectal ultrasound-guided sextant
      prostate biopsies were indicated. RESULTS: Of the men screened, 23.2% (320/1375)
      had serum PSA greater than 4.0 ng./ml. and/or suspicious findings on DRE. Biopsy
      was performed in 199 of 320 (62.1%). Cancer was detected in 21 (1.5%, 21/1375).
      Prostate cancer was found in one case among 154 males (0.65%, 1/154) who were
      screened twice or more. The cancer stage found by screening was significantly
      earlier than that diagnosed at the outpatient clinic (Wilcoxon's rank-sum test: p
      = 0.0047). Receiver operating characteristics analysis showed that the optimal
      free PSA-to-PSA ratio was 12%. Positive predictive value increased from 18% to
      50% when free PSA-to-PSA ratio was combined with PSA. CONCLUSION: 1. Cancer
      detection rate was 1.5% in the mass screening in Mitaka City. 2. Cancer stage
      found by screening was significantly earlier than that diagnosed at the
      outpatient clinic. 3. Free PSA determination might eliminate unnecessary biopsies
      in men with PSA above 4.0 ng./ml with minimal loss of cancer detection.

PMID- 11235140
TI  - [A case report of granulomatous orchitis--review of 20 cases in Japan].
AB  - We report a case of granulomatous orchitis. A 31-year-old male complained of
      right lumbago and scrotal pain. The ultrasonographic finding was multiple hypo
      echoic areas in the right testis as highly suggestive of testicular cancer. The
      diagnosis was made after orchiectomy. Granuromatous orchitis is a rare disease
      which true etiology remains obscure. Only 20 cases have been reported in Japan.
      The clinical, radiological and pathological features of 20 cases are presented
      and discussed. Patients' age ranged from 29 to 79 years, an average of 55 years.
      The left testis was involved in 7 patients, the right in 9 and 4 cases were
      bilateral. Ultrasonographic examination of the affected testis revealed
      hypoechoic mass, so little value in differentiating granulomatous orchitis from
      neoplasm. The correct diagnosis of granulomatous orchitis has never been made
      prior to surgery, because it clinically bears a lot of resemblance to testicular
      cancer. The diagnosis usually is made on histological examination. Orchiectomy is
      the main form of treatment to date, because antibiotics have little effect on the
      course of the disease and at the time of diagnosis, the testis is already
      destroyed and there is hardly any viable testicular tissue in the removed
      specimens.

PMID- 11235142
TI  - [A case of leiomyosarcoma of the renal vein].
AB  - A 54-year-old woman presented with a 6-month history of left back pain. She had
      undergone left mastectomy for breast cancer in 1993 and hysterectomy for cervical
      cancer in 1997. Excretory urography showed no abnormality in the left collecting
      system, but right hydronephrosis caused by a midureteral stone. She was treated
      by transurethral ureterolithotripsy first. Computerized tomography showed a 4 x 3
      cm. mass enhanced slightly by contrast medium at the left renal hilus. The tumor
      was bordered laterally by the left kidney and posteriorly by the left renal vein
      which appeared normal on magnetic resonance imaging. Selective left renal
      angiography revealed no abnormality. Radical en bloc excision of the tumor with
      the left kidney and adrenal gland was performed. Pathological examination showed
      a well differentiated leiomyosarcoma arising from the renal vein; the tumor cells
      stained positive for alpha-smooth muscle actin, vimentin and desmin and negative
      for S 100-protein. She was free of symptoms and there was no evidence of local
      recurrence or distant metastases 22 months postoperatively.

PMID- 11235141
TI  - [Left adrenocortical cancer with inferior vena cava tumor thrombus--a case
      report].
AB  - An 62-year-old male was admitted to our hospital for an evaluation of high grade
      fever, body weight loss and lumbago. He was diagnosed as having a left adrenal
      tumor with intracaval extension and underwent a radical surgery, including
      resection of the tumor, left kidney, spleen and IVC tumor thrombus.
      Histopathological diagnosis was adrenocortical carcinoma with tumor thrombus. To
      our knowledge, our case seems to be the 8th case report of left adrenocortical
      cancer with tumor thrombus extension into IVC. Average survival of reported cases
      was about 15 months. At 4 months after surgery, the patient died due to lung
      metastasis.

PMID- 11235143
TI  - [A case of bilateral renal cell carcinoma showing a rapid course of death in a
      long-term hemodialysis patient due to polycystic kidney].
AB  - A case of bilateral renal cell carcinoma in a 42-year-old polycystic kidney male
      is reported. He had been treated with hemodialysis for 22 years. An abnormal
      small mass was found in one of the left renal cystic lesions by screening
      ultrasonography and CT scan at the 19th year of the hemodialysis. Left radical
      nephrectomy was performed and the histological diagnosis was a renal cell
      carcinoma (RCC). There was no evidence of recurrence and metastasis, however, he
      presented with asymptomatic macrohematuria two years after the operation. CT scan
      demonstrated the rapidly progressing right renal tumor and multiple para-aortic
      lymph node swelling. Right nephrectomy and lymphadenectomy were performed and
      pathological examination showed the advanced RCC with multiple lymph node
      metastasis. Eleven months after the second operation followed by interferon
      therapy. he died of multiorgan metastasis of the RCC. This is the first bilateral
      RCC case in polycystic kidney patient treated with hemodialysis in Japan.

PMID- 11235145
TI  - [How to approach and treat for the patient with endometriosis].

PMID- 11235146
TI  - [Laparoscopic surgery for endometrioma and complete Cul-de-Sac obliteration].

PMID- 11235144
TI  - [Suppressive effects of the antiandrogen flutamide on adrenal androgens in
      advanced prostate cancer patients].
AB  - PURPOSE AND METHODS: We investigated the influence of flutamide on plasma adrenal
      androgens in advanced prostate cancer patients treated with dietylstilbestrol
      diphosphate (DES-DP) followed by luteinizing hormone-releasing hormone agonist
      (LH-RH agonist). Nine patients were enrolled in this study and they were divided
      into the following two treatment groups; group A: LHRH agonist mono-therapy (n =
      4) and group B: LHRH agonist with flutamide (n = 5). For prevention of flare up,
      all patients were treated with DES-DP. RESULTS: Two-week DES-DP administration
      led to reduction of plasma adrenal androgen levels. These levels were kept lower
      for 16 weeks in group B in contrast with group A in which the levels returned to
      the pretreatment levels. Basal ACTH levels in group B were significantly lower
      than those in group A. CONCLUSION: From our observations, we found that flutamide
      reduced adrenal androgen levels in prostate cancer patients treated with LH-RH
      agonist. ACTH suppression might be related to this phenomenon.

PMID- 11235147
TI  - [Medical treatment of endometriosis: general approach].

PMID- 11235148
TI  - [GnRH agonists in the treatment of endometriosis].

PMID- 11235149
TI  - [Novel intermittent GnRHa therapy for patients with endometriosis].

PMID- 11235150
TI  - [Add back therapy for patients with endometriosis].

PMID- 11235151
TI  - [Etiology of endometriosis].

PMID- 11235152
TI  - [GnRH antagonist].

PMID- 11235153
TI  - [Danazol--up-to-date aspect for endometriosis].

PMID- 11235154
TI  - [Low-dose danazol therapy in endometriosis].

PMID- 11235155
TI  - [Local administration of danazol on pelvic endometriosis and uterine
      adenomyosis].

PMID- 11235156
TI  - [Endometriosis and aromatase inhibitor].

PMID- 11235157
TI  - [Combined treatment of endometriosis--medication and surgery].

PMID- 11235158
TI  - [Treatment for endometriosis with pain].

PMID- 11235159
TI  - [Strategy of treatment for infertile women with endometriosis].

PMID- 11235160
TI  - [Laparoscopy in the treatment of endometriosis-associated infertility].

PMID- 11235161
TI  - [Endometriosis-associated infertility and in vitro fertilization].

PMID- 11235162
TI  - [Management of recurrent endometriosis].

PMID- 11235163
TI  - [Recto-vaginal endometriosis].

PMID- 11235164
TI  - [Gastrointestinal endometriosis].

PMID- 11235165
TI  - [Thoracic endometriosis].

PMID- 11235166
TI  - [Endometriosis of the urinary tract].

PMID- 11235167
TI  - [Prevalence of endometriosis in ovarian cancer].

PMID- 11235168
TI  - [Natural history of endometriosis].

PMID- 11235169
TI  - [The biological property of ovarian cancers is affected by endometriosis--with
      special reference to ovarian clear cell adenocarcinoma].

PMID- 11235170
TI  - [Genetic analysis of endometriosis and ovarian cancer].

PMID- 11235171
TI  - [Endometriosis-adenomyosis mouse model induced by transvaginal pituitary
      transplantation].

PMID- 11235172
TI  - [Rat model of endometriosis].

PMID- 11235173
TI  - [Endometriosis and environmental factors].

PMID- 11235174
TI  - [Pathological findings of endometriosis].

PMID- 11235175
TI  - [History and current understanding of endometriosis].

PMID- 11235176
TI  - [Eutopic and ectopic endometrium in endometriosis].

PMID- 11235177
TI  - [Immunological aspects of endometriosis].

PMID- 11235178
TI  - [Peritoneal environment in endometriosis].

PMID- 11235179
TI  - [Molecular genetics of endometriosis].

PMID- 11235180
TI  - [Angiogenic factors in endometriosis].

PMID- 11235181
TI  - [Hormone responsiveness of endometriosis].

PMID- 11235182
TI  - [Apoptosis in endometriosis].

PMID- 11235183
TI  - [Epidemiology of endometriosis].

PMID- 11235185
TI  - [Diagnosis of endometriosis].

PMID- 11235184
TI  - [Clinical symptoms of endometriosis].

PMID- 11235186
TI  - [Classification of endometriosis].

PMID- 11235187
TI  - [Trefoil factor (TFF) and gastrointestinal diseases].

PMID- 11235188
TI  - [Diseases of the digestive tract and telomere lengths: significance and problems
      of telomere measurement].

PMID- 11235190
TI  - [Weekly low dose CPT-11 for multiple lung metastases of colon cancer on an out
      patient treatment: a case report].

PMID- 11235189
TI  - [Efficacy of mesalamine enema in the treatment of steroid-resistant or dependent
      distal ulcerative colitis].
AB  - The efficacy and safety of mesalamine enema were examined in 20 patients with
      steroid-resistant or dependent, distal ulcerative colitis. Rectal bleeding
      disappeared in 3 (18%). 8 (50%) of 16 patients within 2 weeks and 4 weeks after
      the start of mesalamine enema treatment, respectively. Mean clinical activity
      index (CAI) score after the treatment was significantly reduced (8.1-->3.6, p <
      0.001). Furthermore, Mean doses of oral corticosteroid after the treatment (7.3
      mg) were also significantly lower than those before the treatment (12.8 mg) (p <
      0.01). Four patients dropped out. Three patients could not retain the enemas
      because of abdominal discomfort and one patient had fever and rash. There were no
      significant differences in age, gender, disease duration, disease type, and mean
      doses of oral corticosteroid before the treatment between the response group (n =
      8) and the non-response group (n = 8). However, clinical and endoscopic
      activities before mesalamine enema treatment in the non-response group (CAI 9.8,
      Matts score 8.0) were higher than those in the response group (CAI 6.4, Matts
      score 5.5). These results suggest that mesalamine enema is useful for mildly to
      moderately active distal ulcerative colitis by improving clinical symptoms and
      reducing corticosteroid.

PMID- 11235191
TI  - [A case of pediculate carcinoma of the papilla of Vater impacts in horizontal
      part of duodenum].

PMID- 11235192
TI  - [A case of schwannoma of ascending colon].

PMID- 11235193
TI  - [A case of gastrointestinal stromal tumor of jejunum with melana which detected
      by endoscopic examination].

PMID- 11235195
TI  - [A case of adult Reye syndrome].

PMID- 11235194
TI  - [Hepatic resection of recurrent hepatocellular carcinoma post transarterial
      treatment: a case report].

PMID- 11235196
TI  - [A case of autoimmune pancreatitis: follow-up study of imaging].

PMID- 11235197
TI  - [A case of gastrointestinal stromal tumor of the stomach].

PMID- 11235198
TI  - [Acute ultraviolet B induced lens epithelial cell photo-damage and its repair
      process].
AB  - PURPOSE: To clarify the process of acute lens epithelial cell photo-damage
      induced by ultraviolet B (UV-B) exposure and its repair. METHODS: Pigmented
      rabbits were exposed to UV-B (300 mJ/cm2). The time course of lens epithelial
      cell photo-damage was evaluated by light microscopy of lens epithelial cell flat
      mounts. The flat mounted lens epithelial cells were stained with Mayer's
      hematoxylin or by immunohistochemistry with anti-proliferating cell nuclear
      antigen (PCNA) monoclonal antibodies. RESULTS: The lens epithelial cells were
      irregularly arranged and there were debris and pycnotic nuclei, small nuclei,
      existence of large cells, and phagocytosis of neighboring cells in the pupillary
      area. A repair process was seen in the injured areas within a week after UV-B
      exposure. PCNA positive cells were seen and it was confirmed that the healing of
      the photo-injured part was due to epithelial cell proliferation. CONCLUSIONS: The
      acute lens epithelial cell photo-damage induced by UV-B exposure was repaired
      within a week by cell proliferation.

PMID- 11235199
TI  - [Effect of stimulus size on binocular summation within the binocular visual
      field].
AB  - PURPOSE: To study the influence of stimulus sizes on binocular summation using
      the modified Octopus 201 combined with a space synoptophore. METHODS: Four normal
      subjects, aged 21 to 26 were tested. Using the SARGON program, we designed a new
      program to test 37 points in the central 6 degrees visual field. Sensitivity of
      the central 6 degrees visual field under monocular and binocular conditions was
      measured while the fusion patterns were displayed on the space synoptophore. The
      visual fields were measured at stimulus sizes 1, 3, and 5. RESULTS: The visual
      sensitivity under binocular conditions was higher than under monocular conditions
      for all the stimulus sizes. Binocular summation for stimulus size 1 was present
      in a flat form, for stimulus size 3 in a convex form, and for stimulus size 5 in
      a concave form in the central 6 degrees visual field. CONCLUSION: Binocular
      summation differed in stimulus size and retinal eccentricity. Binocular summation
      for stimulus size 3 increased in the fovea and it increased for stimulus size 5
      in the peripheral area in the central 6 degrees visual field.

PMID- 11235200
TI  - [Apparent size of stereoscopic images with disparity in relation to the function
      of accommodation].
AB  - PURPOSE: We investigated experimentally the relationship between the apparent
      size of stereoscopic images with disparity and the accommodative function.
      METHODS: The judgement of the apparent stereoscopic image size used the subject
      reply. The size of the forward image, which was produced by crossed visual lines
      with binocular disparity and by a time-sharing type stereoscopic three
      dimensional display using liquid crystal shutter glasses, was compared with the
      size of the plane image. The size of the backward image produced by uncrossed
      visual lines was also compared with the size of the plane image. Sixteen normal
      volunteers were requested to subjectively compare each image with the original
      plane image on the display screen in relation to its size. Accommodation was
      measured using an infrared optometer to record the step responses (from far to
      near, and near to far). The subjects were divided into two groups, a fast
      response group and slow response group. RESULTS: It was found that the forward
      image was smaller than the plane image and the backward image was larger than the
      plane image, and this tendency was remarkable in the fast response group.
      CONCLUSION: From these results, it appears that the state of accommodation
      affects the perceived size of stereoscopic images with disparity.

PMID- 11235201
TI  - [Ocular surface changes after dacryocystorhinostomy].
AB  - PURPOSE: To observe changes in tear film lipid interference patterns on the
      ocular surface in patients with nasolacrimal duct (NLD) obstruction before and
      after dacryocystorhinostomy (DCR). METHODS: The tear film lipid layer on the
      ocular surface was observed with a specular reflection video recording system in
      5 eyes of 4 patients with NLD obstruction before and after DCR. Precorneal tear
      lipid layer interference patterns at the central cornea, tear meniscus height
      (TMH), and the Shirmer I test were recorded. Observed patterns were classified
      into 5 grades. RESULTS: Three of four eyes with TMH values over 0.4 mm before DCR
      showed decreased TMH postoperatively. One eye with a TMH of 0.2 mm showed no
      change after DCR. Concerning the tear film lipid layer interference patterns, 4
      eyes were classified as grade 1 or 2, and 1 eye was classified as grade 4 before
      DCR. After DCR, the 5 eyes were classified from grade 3 to grade 4. Epiphora was
      successfully resolved in all patients after DCR. CONCLUSION: Tear film lipid
      layers were classified as normal grades before DCR but most cases changed to high
      grades after DCR. We suggest that the eye after DCR should have a thicker lipid
      layer than before DCR.

PMID- 11235203
TI  - [Psychophysics in ophthalmology].

PMID- 11235202
TI  - [Factors related to intraoperative retinal breaks in macular hole surgery].
AB  - PURPOSE: To evaluate the factors of intraoperative retinal breaks in macular hole
      surgery. METHODS: This study included 558 eyes of 506 patients who underwent
      idiopathic macular hole surgery by one surgeon. Multiple regression was performed
      using the variables of gender, age, affected eye, lens status, stage, duration of
      symptoms, hole size, axial length, and lattice degeneration. RESULTS: The rate of
      retinal breaks was higher in stage 3 (16.0%) than in stage 4 (8.2%) (p = 0.014).
      In eyes with lattice degeneration intraoperative retinal breaks occurred in about
      40% of the cases. Major factors were as follows: lattice degeneration (r = 0.24,
      p < 0.0001) in all eyes, stage (r = 0.090, p = 0.048) in eyes without lattice
      degeneration, and gender (r = -0.18, p = 0.035) in eyes of stage 4 without
      lattice degeneration. CONCLUSIONS: The factors of intraoperative retinal breaks
      in macular hole surgery were lattice degeneration in all eyes and stage 3 in eyes
      without lattice degeneration. The high incidence of intraoperative retinal breaks
      in stage 3 was mainly due to the occurrence of posterior vitreous detachment.
      Male gender was a significant factor associated with intraoperative retinal
      breaks.

PMID- 11235204
TI  - [Effects of stimulus intensity on multifocal electroretinograms].
AB  - PURPOSE: To investigate origins of responses of the second order kernel
      components of multifocal electroretinograms (m-ERGs), the influence of stimulus
      intensities on the waveform were studied. SUBJECTS AND METHODS: M-ERGs were
      recorded from 20 normal eyes of 14 normal adults using a Visual Evoked Response
      Imaging System with 19 hexagonal stimulus elements with light intensities of 6.3,
      20, 63, 200, or 331 cd/m2. The response densities and implicit times of the first
      (N1, P1, N2) and the second order kernel components (P1, N1, P2, N2, P3, N3) of
      the m-ERGs were measured. RESULTS: The components were divided into two groups
      based on the behavior of the each component to the stimulus intensity change. The
      first group consisted of all the first order kernel components and P1 and N1 of
      the second order kernel components whose response densities were significantly
      larger (p < 0.05) than those of components elicited by stimulus of one grade
      lower intensity. The second group consisted of N2, P3, and N3 of the second order
      kernel components whose response densities did not increase when the stimulus
      intensity was increased from 200 to 331 cd/m2. CONCLUSION: It is probable that in
      the second order kernel components, the origin of P1, N1, and P2 is different
      from N2, P3, and N3 because the response to stimulus intensity of the two groups
      of components was different.

PMID- 11235205
TI  - [Presence of alpha 5 beta 1 integrin and fibronectin in the anterior subcapsular
      cataract].
AB  - PURPOSE: We investigated whether alpha 5 beta 1 integrin and fibronectin were
      present in myofibroblast-like lens epithelial cells in anterior subcapsular
      cataract (ASC). METHODS: Nine anterior capsule specimens were obtained from the
      patients during cataract surgery and frozen for cryostat sections. Six specimens
      were anterior capsule obtained from cataract with ASC. As a control, three
      specimens were obtained from cataract without ASC. Alpha-smooth muscle actin
      (alpha-SMA), alpha 5 beta 1 integrin, and fibronectin were detected by
      immunohistochemical observation. RESULTS: In all 6 specimens from patients with
      ASC, the lens epithelial cells around fibrosis tissue included myofibroblast-like
      lens epithelial cells which were positive for alpha-SMA. alpha 5 beta 1 integrin
      was detected in these lens epithelial cells. Fibronectin was also detected around
      these myofibroblast-like lens epithelial cells. Three control specimens showed no
      immunoreactivity against alpha-SMA, alpha 5 beta 1 integrin, or fibronectin.
      CONCLUSIONS: Alpha 5 beta 1 integrin and fibronectin may play an important role
      in myodifferentiation of lens epithelial cells.

PMID- 11235206
TI  - [Quantitative assessment of macular appearance with a scanning laser
      ophthalmoscope in aging or diabetic retinopathy patients].
AB  - PURPOSE: Changes in the macula caused by aging or diabetic retinopathy were
      studied with scanning laser ophthalmoscope (SLO). METHODS: SLO imaging of the
      macula was done with argon blue, argon green, helium neon, and diode lasers, and
      the images were recorded on s-VHS video tape. In this study, we examined 29
      patients (58 eyes) with no retinal organic change as controls, 8 diabetic
      patients (16 eyes) without retinopathy, 8 patients (16 eyes) with simple diabetic
      retinopathy, and 6 patients (12 eyes) with preproliferative diabetic retinopathy.
      RESULTS: As age increased, the dark area of the macula was enlarged in the argon
      blue and argon green images. In diabetic patients, the dark area of the macula in
      patients in their 30 s and 40 s with retinopathy was larger than in diabetic
      patients without retinopathy (p < 0.05). The dark area of the macula in
      preproliferative diabetic retinopathy was larger than in patients in their no
      diabetic retinopathy or simple diabetic retinopathy (p < 0.05). In the 50 s and
      60 s, the dark area of the macula in preproliferative diabetic retinopathy was
      larger than in the controls or in patients with no diabetic retinopathy (p <
      0.05). CONCLUSION: The macular dark area became enlarged with aging. In diabetic
      patients, the dark area of the macula was enlarged in diabetic patients without
      retinopathy or with progression in diabetic retinopathy stage. Therefore,
      quantitative assessment of macular appearance with SLO can be used as a new
      clinical index.

PMID- 11235207
TI  - [Operculum in idiopathic macular holes].
AB  - PURPOSE: To detect the factors related to the operculum in idiopathic macular
      holes and present a pathogenesis of idiopathic macular holes. METHODS: This study
      included 583 eyes of idiopathic macular hole that underwent macular hole surgery.
      To detect the factor related to the operculum, the variables of age, duration of
      symptoms, hole size, preoperative visual acuity, refraction, axial length,
      refraction axial length ratio were used for the comparison between two groups and
      multiple regression. The success rate of surgery and postoperative visual acuity
      were examined whether the operculum was present or not. RESULTS: The variables
      that were significantly related to the operculum were as follows: refraction
      axial length ratio (r = 0.18, p = 0.0092) in women of stage 3, duration of
      symptoms (r = -0.44, p < 0.001), preoperative visual acuity (r = -0.33, p =
      0.0025), and refraction axial length ratio (r = -0.22, p = 0.020) in women of
      stage 4, and age (r = 0.19, p = 0.047) in men of stage 3. There were no
      significant differences in the success rate of surgery and postoperative visual
      acuity whether the operculum was present or not. CONCLUSIONS: Generally,
      operculum tends to occur in aged and round eyes and possibly does not occur in
      younger and back projected eyes because of retinal fissure. In women of stage 4,
      the operculum is possibly a torn retina and does not occur in atrophic holes.

PMID- 11235208
TI  - [Regulation of a small GTPase Rap2].
AB  - Rap2 is a member of Ras-family G proteins and related most closely to Rap1;
      however little is known about the regulation of Rap2 activity. In this study, I
      have compared the regulation and function of Rap2 with those of Rap1. In 293T
      cells, Rap2 was regulated by the same set of guanine nucleotide exchange factors
      (GEFs) and GTPase-activating proteins (GAPs) as those which regulated Rap1. Rap2
      was localized at both plasma membrane and intracellular membrane compartments, as
      Rap1 was. Rap2 bound to the Ras-binding domain of Raf and inhibited Ras-dependent
      activation of Elk1 transcription factor. I have found that the GTP-bound form
      exceeds 50% of total Rap2 in the cells. This observation suggests that Rap2
      suppresses Ras-mediated activation of ERK/MAP kinase cascade in quiescent cells.

PMID- 11235209
TI  - [L-glutamine-induced heme oxygenase-1 protects small intestine from warm ischemia
      and reperfusion injury in the rat].
AB  - Although it is considered that L-Glutamine (L-Gln) supplementation improves gut
      morphology and survival in animal models such as radiation and drug-induced
      enterocolitis, the mechanisms underlying are far from being established.
      Recently, Gln has been reported to give protection against stress in in vitro
      intestinal epithelial cell lines through the induction of heat shock proteins
      (HSPs). This study is designed to examine whether L-Gln may induce cytoprotective
      molecules such as heme oxygenase-1/HSP32 (HO-1) and reduced glutathione (GSH) in
      in vivo intestinal tissues, and to clarify whether these molecules may play a
      role in warm ischemia and reperfusion (I/R) injury. We measured the releases of
      serotonin and tumor necrosis factor-alpha (TNF-alpha), and graft survival as
      viability assays following reperfusion of warm ischemically injured intestinal
      grafts. The substantial expression of HO-1 after L-Gln administration was
      observed in villous epithelial cells, crypts and muscular layers, and peaked at 6
      h, while that of the control group pretreated with lactated Ringer (LR) solution
      was observed throughout tissues to be slightly similar to those of fresh
      untreated tissues. Tissue GSH contents slightly increased 24 h after
      administration and were less reduced through the periods of I/R than those of the
      LR group. Releases of serotonin and TNF-alpha in L-Gln group were attenuated
      during the brief periods of warm ischemia, compared with those in the LR group. A
      significant graft survival rate was also observed between both groups (6/6 of L
      Gln group vs. 1/6 of LR group; p < 0.05). In conclusion, the protective effects
      of L-Gln in small intestines against warm I/R injury were considered to be in
      part mediated by up-regulation of molecules such as HO-1 and GSH via cellular
      antioxidant activity. Thus, L-Gln pretreatment may represent an innovative
      approach to the prevention of complex I/R injury.

PMID- 11235210
TI  - [Introduction of ongoing research projects on echinococcosis at Asahikawa Medical
      College and some comments on the surveillance, prevention and control of alveolar
      echinococcosis in Japan].
AB  - All researchers working at Department of Parasitology, Asahikawa Medical College
      (AMC) have been involved in either basic or applied research on echinococcosis
      (alveolar echinococcosis; AE, cystic echinococcosis; CE) and neurocysticercosis
      (NCC). As these parasitic diseases are 1) most serious helminthic infections
      threatening human life, 2) caused by the larval stage of very closely related
      taeniid cestodes and 3) recognized as global emerging parasitic diseases, we have
      to establish research reference center for differentiation of these diseases,
      since the recommendations for the treatment of these three diseases differ
      critically. We at AMC have already established highly reliable differential
      serodiagnosis for these all using native antigens and recombinant antigens for AE
      and NCC. Based on such scientific contribution, we have been involved in many
      international collaboration projects on AE, CE and NCC in Asia, Europe, Africa
      and America. Basic research from mitochondrial DNA analysis of Echinococcus
      multilocularis (causative agent of AE) and Taenia solium (NCC) has revealed
      and/or implied the origin of the polymorphism of these parasites in the world and
      diversity of pathogenicity. Epidemiological surveillance of AE in China has
      strongly suggested that the risk factor is dog carer but not dog feces, dog
      owned, wild herbs or fox hunting. As the ongoing serology in Hokkaido carried out
      by the Hokkaido Institute of Public Health is for the primary screening of AE, it
      is impossible to identify AE patients. It is, therefore, recommended that
      serology for identification of AE without surgical confirmation is the key to be
      introduced for differentiation of AE patients, either asymptomatic or
      symptomatic, in order to recognize the incidence of AE in Hokkaido. Without the
      true incidence of AE, it is impossible to establish any reliable systems for the
      surveillance, prevention and control of AE in Hokkaido, Japan.

PMID- 11235211
TI  - [Analysis of infiltrating T cells in the affected autoimmune lesions of HTLV-I
      transgenic rats].
AB  - Human T-cell leukemia virus type I(HTLV-I) is known to be associated with a
      number of disorders, inducing adult T cell leukemia, myelopathy, arthropathy,
      uveitis, and probably Sjogren's syndrome, T cell alveolitis, polymyositis, and
      infective dermatitis. To investigate the pathogenetic role of HTLV-I in these
      clinical disorders, we established a transgenic rat model carrying the env-pX
      gene of HTLV-I(env-pX rat), which develops arthritis, myocarditis, dermatitis,
      necrotizing arteritis, myositis and sialoadenitis. Several autoantibodies, such
      as anti-nuclear and anti-cardiolipin antibodies and rheumatoid factor, were
      detected in the sera. Peripheral T lymphocytes of env-pX rats expressed co
      stimulatory molecules and showed hyper-immune reactivity to various stimulation
      in vitro. In this study, to characterize major pathogenic autoantigens in the
      affected lesions, the author examined the clonalities of T cells in the spleen
      and of infiltrating T cells in the skin lesions as well as affected joints of env
      pX rats by single strand conformation polymorphism (SSCP) of polymerase chain
      reaction-amplified cDNA fragments of T cell receptor (TCR) V beta. No specific
      expansion of particular T cell clones was evident in the spleen of env-pX rats.
      Oligoclonal T cell expansions were observed in both infiltrating T cells of the
      affected joints and skin lesions, but no specific T cell clones common in the two
      lesions expanded in env-pX rats. Also, no specific amino acid motif in the
      complementarity determining region 3 of TCR V beta was evident in the affected
      joints. Those results suggest that the locally expanded T cell clones against
      various autoantigens of the joint or skin induced by the transgene may play major
      pathogenetic roles in development of autoimmune diseases in env-pX rats. On the
      other hand, env-pX rats easily developed arthritis by immunization of type II
      collagen and the SSCP patterns of accumulated T cell clonotypes in the arthritis
      were similar to those of arthritis developed in env-pX rats without immunization.
      The evidence suggests that the type II collagen-immunization may be a trigger to
      develop the inherent arthritis of env-pX rats.

PMID- 11235212
TI  - [Taranscranical magnetic stimulation (TMS) and rehabilitation medicine].

PMID- 11235213
TI  - [The sensitivity and clinical implications of periodical bladder biopsy following
      transurethral resection of superficial bladder transitional cell carcinoma].
AB  - The role of the periodical bladder biopsy after transurethral resection (TUR-Bt)
      of superficial bladder cancer (sBT) was evaluated. Sixty-four patients (85 TURs)
      with sBT who underwent TUR-Bt between 1993 and 1998 were divided into 14 (22
      TURs) who had carcinoma in situ (CIS) at the first TUR (group A), and 50 (64
      TURs) who had papillary tumors without concomitant CIS (group B). Post-TUR
      intravesical instillation was performed with bacillus Calmette-Guerin for the
      majority of group A, and mitomycin C for the majority of group B. The first
      biopsy was performed at 3 months postoperatively, and the second biopsy was done
      at 8 to 12 months postoperatively. The mean observation time was 4 years and 6
      months. Residual cancer was detected in 7 out of 34 biopsies (20.6%) in group A,
      and 19 out of 94 (20.2%) in group B. Every residual lesion in group A was CIS
      with negative cytology. In group B, with exclusion of 11 recurrent papillary
      tumors, the detection rate was only 8/83 (9.6%). In both groups, even in the
      cases with no sign of disease in biopsies, the recurrence immediately after the
      termination of the biopsy protocol was common. The progression of the cancer was
      more frequent in group A (4 patients), than in group B (2 patients) (p < 0.01,
      log-rank test), and no case in group B showed local progression. The periodical
      biopsy may have a certain, but limited advantage over conventional examinations.
      A less invasive and more sensitive method in awaited.

PMID- 11235214
TI  - [Prostatic cancer developing after transurethral resection of the prostate for
      benign prostatic hyperplasia].
AB  - From January 1993 to June 1998, 319 cases were histopathologically diagnosed as
      prostatic cancer. In 7 of the 319 cases (2.2%) transurethral resection of the
      prostate (TUR-P) had been performed and a diagnosis of benign prostatic
      hyperplasia had been made with the resected specimens. The interval between TUR-P
      and the diagnosis of prostatic cancer ranged from 22 months to 15 years. All the
      cases showed an elevation of the prostate specific antigen (PSA) value (6.4-399
      ng/ml, Tandem-R: RIA) at the time of cancer diagnosis. In 2 cases, PSA was
      measured in cancer screening. The clinical stage was stage B1 in 2 cases, stage
      B2 in 2 and D2 in 3. Only one case had been regularly followed-up after TUR-P, in
      which cancer was diagnosed by needle biopsy 22 months after TUR-P, because of the
      sustained high PSA values. Since most of such patients have an advanced stage of
      prostate cancer, it is of importance to have periodical follow-up examinations
      after TUR-P. The measurement of PSA appears the most reliable means in this way.

PMID- 11235215
TI  - [The efficacy and safety of terazosin and tamsulosin in patients with urinary
      disturbance accompanying prostatic hypertrophy].
AB  - Terazosin (TE) and tamsulosin (TA) were allocated randomly to 38 patients who had
      urinary disturbance accompanying prostatic hypertrophy, and the efficacy and
      safety of the drugs were examined. Subjective symptoms due to I-PSS were improved
      significantly in both TE and TA groups. On the other hand, objective symptoms
      such as the maximum urinary flow and mean urinary flow were improved more in the
      TE group. TE showed hypotensive and cholesterol-decreasing effects in patients
      who also had hypertension and hyperlipemia. No unknown adverse reactions were
      observed in either groups, and the drugs were shown to be highly safe. TE was
      considered to be useful as the first choice drug for the patients with
      hypertension and or hyperlipemia and those with severe objective symptoms. TA was
      considered to be useful for the patients with impaired drug compliance or those
      with severe subjective symptoms though objective symptoms were not so severe.

PMID- 11235216
TI  - [Old adrenal hematoma: a case report].
AB  - A 75-year-old man was admitted to our hospital for closer examination of a left
      mass. Warfarin and calcium-antagonist for arrhythmia and hypertension had been
      administered for about 2 months before admission to our ward. Abdominal
      ultrasonography revealed a left adrenal mass 5 cm in diameter. Only serum
      noradrenalin was slightly elevated in endocrinological studies. In 131I-MIBG
      scintigraphy, uptake of radio-isotope at the adrenal gland was not revealed.
      Computed-tomographic (CT) scan showed left adrenal mass with a low density in the
      central area and iso-density in the peripheral area. The enhanced CT scan
      revealed enhancement in only the peripheral area of the left adrenal gland.
      Magnetic resonance imaging (MRI) showed a different intensity in the central area
      or peripheral area. Only the peripheral area of the mass was enhanced on dynamic
      MRI. Left adrenalectomy was performed. Histopathological examination revealed an
      old hematoma in the adrenal medulla without neoplasmic cells or vascular lesions.

PMID- 11235217
TI  - [A case of renal oncocytoma with synchronous contralateral renal cell carcinoma].
AB  - A case of bilateral, synchronous renal cell carcinoma and oncocytoma is reported.
      The patient was a 70-year-old woman. Computed tomographic scan revealed bilateral
      low density masses, which had a diameter of approximately 4 cm (right kidney),
      and 2.5 cm (left kidney). We suspected bilateral renal cell carcinomas, and
      performed, right nephrectomy and left enucleation of the tumor. Pathological
      diagnosis was right renal cell carcinoma and left oncocytoma. To our knowledge
      only 5 previous cases of renal cell carcinoma associated with oncocytoma have
      been reported in Japan. Two cases were metachronous and three cases were
      unilateral and synchronous. This is the first reported case of bilateral,
      synchronous renal cell carcinoma and oncocytoma.

PMID- 11235218
TI  - [Enucleation of renal tumor using microwave tissue coagulator: a case report].
AB  - A 69-year-old man was referred to our department for a cystic tumor, 4.0 cm in
      diameter, in the lower portion of the right kidney, which was detected by
      computed tomography. The patient had been admitted to the department of surgery
      in our hospital for treatment of ileus caused by transverse colon cancer. With a
      diagnosis of cystic renal cell carcinoma. T2N0M0, in situ non-ischemic tumor
      enucleation was performed using a microwave tissue coagulator (Microtaze, Heiwa
      Electronics Industry Inc., Tokyo). The enucleation was accompanied by a defect of
      the renal pelvis, but it was easily repaired. The operation time was 120 minutes
      and blood loss was 110 cc. The histological diagnosis was renal cell carcinoma,
      pT2N0M0V1, expansive, alveolar type, clear cell subtype, G1 > G2. Diagnostic
      imaging done postoperatively showed no sign of damage to renal function. At the
      present time, the patient has been disease-free with interferon-alpha for 12
      months and is being followed on an outpatient basis. In this report, the
      advantages of nephron-sparing surgery, especially in situ non-ischemic tumor
      enucleation using a microwave tissue coagulator for renal tumor are discussed. In
      particular, the technique of performing tumor enucleation with repair of the
      defect of renal pelvis used in this case may extend the indication of nephron
      sparing surgery.

PMID- 11235219
TI  - [A case of tumor-forming chronic pyelonephritis that was difficult to be
      differentiated from renal cell carcinoma].
AB  - We experienced a rare case of tumor-forming type of chronic pyelonephritis that
      could hardly be differentiated from renal cell carcinoma. A 62-year-old man was
      admitted to our department with right renal tumor which was discovered when he
      underwent examination for gastric cancer. Abdominal ultrasound sonography and
      computed tomography revealed a mass in the middle portion of the right kidney,
      measuring 3.8 x 3.5 cm in diameter, with irregular surface and isoechoic and
      isodense inner mass. Renal angiography demonstrated a hypervascular area in the
      middle portion. Radical nephrectomy and subtotal gastrectomy were performed under
      a tentative diagnosis of right renal cell carcinoma and early gastric cancer. The
      excised specimen macroscopically demonstrated a yellowish mass in the middle
      portion and microscopically revealed many lymphocytes and few neutrophils,
      macrophages or foam cells. The patient was diagnosed as tumor-forming type of
      chronic pyelonephritis. Such obvious inflammatory findings very rarely exist in
      the tumor-forming type of chronic pyelonephritis. Therefore, caution should be
      exercised in the differential diagnosis between this disease and renal cell
      carcinoma.

PMID- 11235220
TI  - [Rupture of renal pelvis due to urolithiasis: report of two cases].
AB  - Two cases of renal pelvis rupture caused by urolithiasis are reported. The first
      case was in a 62-year-old male who had left flank pain. Urological examination
      including drip infusion pyelography (DIP) and abdominal computed tomography (CT)
      revealed a spontaneous rupture of the left renal pelvis. The rupture was assumed
      to have been caused by a small ureteral stone. The stone passed spontaneously,
      and the extravasation disappeared with conservative therapy. The second case was
      in a 84-year-old male who was admitted with high fever. Urological examination
      including DIP and abdominal CT showed a suspected rupture of the left renal
      pelvis due to a renal stone at the ureteropelvic junction. Percutaneous
      nephrostomy was performed and antegrade pyelography showed extravasation from the
      left renal pelvis. Extravasation disappeared on the 12th postoperative day.
      Extracorporeal shock wave lithotripsy was performed three times. The renal stone
      was completely discharged and the nephrostomy tube was removed successfully.

PMID- 11235221
TI  - [A case of squamous cell carcinoma of the bladder that was successfully treated
      with multidisciplinary therapies].
AB  - A 45-year-old man with hematopyuria detected at another hospital visited our
      department for further examination. Endoscopic examination revealed a
      disintegration abscess between the bladder neck and prostatic urethra.
      Transurethral biopsy demonstrated squamous cell carcinoma of the bladder. He
      received 40 Gy of radiation combined with M-VAC (methotrexate, vinblastine,
      dovorubicin cisplatin) chemotherapy. Pathologically, a complete response was
      found when he underwent total cystourethrectomy. There has been no sign of
      recurrence for one and a half years postoperatively.

PMID- 11235222
TI  - [A case of human chorionic gonadotropin-producing bladder cancer].
AB  - An 86-year-old man consulted our hospital complaining of gross hematuria.
      Cystoscopy revealed a nodular broad-based cancer at the dome of the bladder. The
      patient was initially treated by transurethral resection of bladder tumor. Since
      histological examination showed grade 3 transitional cell carcinoma containing
      giant cells that were positive for beta-human chorionic gonadotropin (beta-HCG),
      we made a diagnosis of beta-HCG-producing bladder cancer. Because of his advanced
      age and poor general condition, the patient underwent partial cystectomy alone
      without adjuvant chemotherapy. One month later, a chest X-ray film revealed
      multiple lung metastases, and he developed paraplegia of the lower extremities
      suggesting spinal metastases. One month later, he was brought to our hospital
      with cardiopulmonary arrest. This is, to our best knowledge, the 22nd case report
      of beta-HCG-producing bladder cancer in Japan.

PMID- 11235223
TI  - [A survey of radical surgery without neoadjuvant therapy for patients with stage
      B and C prostatic carcinoma].
AB  - There has been much controversy regarding radical surgery for both localized and
      locally extensive carcinoma of the prostate. We analyzed the outcome of radical
      prostatectomy and the preoperative evaluation in order to assess the indication
      of radical prostatectomy. Fifty-six patients with clinical stage B or C prostate
      cancer were treated by radical prostatectomy without neoadjuvant therapy.
      Endocrine therapy was added to the non-curative cases postoperatively.
      Preoperative evaluation was compared with pathological results and survival, and
      furthermore the usefulness of the preoperative PSA and PSA half-life were
      investigated. The mean follow-up period was 44.5 months. The accuracy of the
      grade and the clinical stage were 58.9% and 23.2%, respectively. Organ-confined
      disease was seen in patients with an initial PSA level less than 30 ng/ml.
      Postoperative PSA half-life is significantly prolonged in cases with poorly
      differentiated adenocarcinoma or lymph node involvement and may be a predictor of
      PSA failure. The cause-specific 5-year survival rates were 92.7% on the whole,
      92.9% for well differentiated, 96.7% for moderately differentiated, 85.7% for
      poorly differentiated, 100% for stage B1, 95.0% for stage B2 and 86.8% for stage
      C. These results indicated that patients with an initial PSA level of less than
      30 ng/ml will benefit from radical prostatectomy.

PMID- 11235224
TI  - [A case of female urethral diverticulum calculus associated with multiple
      sclerosis].
AB  - We report a case of urethral diverticulum with a calculus in a 52-year-old
      female. She had suffered from transverse myelopathy (flaccid paralysis) as a
      result of multiple sclerosis. She presented with total incontinence and urinary
      tract infection that did not respond to antibiotic therapy. We found a urethral
      diverticulum calculus by X-ray imaging and urethroscopy. Transvaginal urethral
      diverticulectomy with removal of stone was carried out without any complications.
      The removed stone was 35 x 31 x 19 mm in size and was composed of magnesium
      ammonium phosphate and calcium phosphate.

PMID- 11235225
TI  - [A case of giant small cell carcinoma of the prostate].
AB  - A 64-year-old man having backbone pain was referred to our institute, and
      laboratory examinations revealed that he was suffering from severe renal failure.
      Abdomino-pelvic CT revealed bilateral hydronephrosis, a giant prostate over 500 g
      in weight, and multiple para-aortic lymph node metastasis. Histological diagnosis
      of the prostate was small cell neuroendocrine carcinoma. Serum neuron-specific
      enolase (NSE) level was slightly high reflecting the positive immunohistochemical
      staining, but serum PSA remained within normal limits. The patient was treated
      with hormone-chemotherapy after successful treatment of the renal failure, but he
      died on the 74th hospital day. Small cell carcinoma is known to have a high rate
      of malignancy and metastasis from an early stage. Several giant prostatic tumors
      have been reported previously, but this case is considered to be the second
      gigantic small cell carcinoma in the Japanese literature.

PMID- 11235226
TI  - [Successful complete androgen blockade (CAB) therapy for prostatic cancer
      detected from multiple lung metastases: a case report].
AB  - Prostatic cancer is rarely diagnosed by detection of lung metastases. We report a
      case of prostatic cancer in a 73-year-old man detected by abnormalities in chest
      X-ray and serum prostate specific antigen (PSA) level. He was initially admitted
      to our hospital due to elevation of PSA level. On the first transperineal
      prostatic needle biopsy, prostatic cancer was not detected and he was followed.
      Seven months after the first biopsy, chest X-ray revealed multiple abnormal
      nodules in the lung fields bilaterally and PSA level was again elevated. A second
      prostatic biopsy and whole-body examination were performed, and he was diagnosed
      with moderately differentiated prostatic adenocarcinoma with multiple lung
      metastases. Complete androgen blockade therapy was performed immediately. Two
      months after the beginning of treatment, PSA level was normalized and the
      multiple lung metastases had completely disappeared. There has been no evidence
      of recurrence or PSA relapse 24 months after detection of the prostatic cancer.
      This is the 26th case of prostatic cancer diagnosed in Japan following detection
      of multiple lung metastases.

PMID- 11235227
TI  - Effect of renovating an office building on occupants' comfort and health.
AB  - An intervention study was performed in a mechanically ventilated office building
      in which there were severe indoor climate complaints among the occupants. In one
      part of the building a new heating and ventilation strategy was implemented by
      renovating the HVAC system, and a carpet was replaced with a low-emitting vinyl
      floor material; the other part of the building was kept unchanged, serving as a
      control. A comprehensive indoor climate investigation was performed before and
      after the intervention. Over a 2-week period, the occupants completed a daily
      questionnaire regarding their comfort and health. Physiological examinations of
      eyes, nose and lungs were performed on each occupant. Physical, chemical and
      sensory measurements were performed before and after the intervention. The
      renewal of the flooring material was performed after a sensory test of
      alternative solutions in the laboratory. Before the floor material was installed
      in the office building, a full-scale exposure experiment was performed in the
      laboratory. The new ventilation strategy and renovation of the HVAC system were
      selected on the basis of laboratory experiments on a full-scale mock-up of a
      cellular office. The severity of occupants' environmental perceptions and
      symptoms was significantly reduced by the intervention.

PMID- 11235228
TI  - Acoustic rhinometry and lavage biomarkers in relation to some building
      characteristics in Swedish schools.
AB  - It has been suggested that certain building factors can be associated with
      specific exposures, such as dampness, chemical emissions and dust. The aim of the
      study was to examine the relationships between some selected building factors, on
      the one hand, and signs of inflammation or obstruction in the upper airways on
      the other. Acoustic rhinometry and nasal lavage were used in a field study among
      234 school personnel in 12 randomly selected schools (participation rate 84%).
      Eosinophil cationic protein (ECP), lysozyme, albumin and myeloperoxidase (MPO)
      were analyzed in the lavage fluid. Building related factors selected for the
      study were: roof inclination, fundament, building construction, signs of water
      damage, floor material, building age, ceiling height, bookcases and plants in the
      classroom. Control was made for potential confounders. The results indicate a
      pattern of nasal responses: less patent noses and an inflammatory biomarker
      response could be related to flat roof and a concrete slab fundament, factors
      that are known risk factors for water leakage, building dampness and possibly
      microbial growth. A reduced nasal patency without an inflammatory biomarker
      response was related to factors associated with plasticizers and dust. Positive
      effects were observed for plants in the classroom and in older buildings.

PMID- 11235229
TI  - A survey of environmental tobacco smoke controls in California office buildings.
AB  - A survey of environmental tobacco smoke (ETS) controls in California office
      buildings was carried out to obtain information of the type and distribution of
      ETS controls in office buildings and to evaluate the effectiveness of various ETS
      controls. A total of 118 smoking areas in 111 county and city buildings were
      inspected to collect information on the type of ETS controls. Only 31% of the
      smoking areas inspected were physically separated from nonsmoking areas with full
      floor-to-true-ceiling walls, 25% exhausted air to the outside, and 38% did not
      recirculate air to non-smoking areas. A total of 23 smoking areas and their
      adjacent non-smoking areas in 21 buildings were monitored for nicotine and
      fluorescent particulate matter (FPM). A tracer gas, sulfur hexafluoride (SF6),
      was released in smoking areas to measure the air leakage from smoking areas to
      adjacent non-smoking areas. The measurements of nicotine, FPM, and SF6 have shown
      large variations of the effectiveness of ETS controls. The least effective type
      of smoking area studied were open areas with no physical barriers between smoking
      and nonsmoking areas, no exhaust to the outside and no return air separation. On
      the contrary, smoking rooms with three ETS controls (i.e., physical separation,
      exhaust to outside, and no air recirculation) were the most effective design in
      containing ETS within smoking areas.

PMID- 11235230
TI  - Characterization of particulate emissions from occupant activities in offices.
AB  - This paper characterizes the relationship between occupant activities and indoor
      air particulate levels in a non-smoking office building. Occupant activities were
      recorded on video. Particulate concentrations were monitored by three optical
      particle counters (OPCs) in five size ranges at three heights. Particulate mass
      concentrations were measured gravimetrically and bioaerosol concentrations were
      determined by impaction methods. Occupant activities and number concentrations
      were determined with 1-min resolution over a 1-week period. Occupant activities
      such as walking past or visiting the monitoring site explained 24-55% of the
      variation of 1- to 25-micron diameter particle number concentrations. Statistical
      models associating particulate concentrations with occupant activities depended
      on the size fraction and included an autocorrelative term. Occupant activities
      are estimated to contribute up to 10 micrograms m-3 in particulate concentrations
      per person. Number concentrations of particles smaller than 1 micron had little
      correlation with indoor activities other than cigarette smoking and were highly
      correlated with outdoor levels. The method can be used to characterize emissions
      from activities if rapid measurements can be made and if activities can be coded
      from the video record.

PMID- 11235231
TI  - Volatile organic compounds, polycyclic aromatic hydrocarbons and elements in the
      air of ten urban homes.
AB  - Ten homes were monitored at regular intervals from June 1994 through April 1995
      as part of a Public Health Assessment in Southeast Chicago for exposure to
      volatile organic compounds (VOCs), polycyclic aromatic hydrocarbons (PAHs), and
      elements. Simultaneous 24-h indoor and outdoor samples were collected. VOCs were
      and analyzed using USEPA Method TO-14 with Selected Ion Monitoring Mass
      Spectrometry (GC/MS). PAHs were analyzed using USEPA Method TO-13 with GC/MS.
      Elements were collected on quartz fiber filters and analyzed by Inductively
      Coupled Argon Plasma (ICP) spectroscopy or Graphite Furnace Atomic Absorption
      (GFAA). Continuous measurements of CO2 and temperature were recorded for each
      indoor sample. Twenty-four h total CO2 emissions were determined from occupancy
      and estimated gas stove usage and were moderately correlated (R2 = 0.19) with 24
      h average indoor CO2 concentrations. Modeled 24-h air exchange rates ranged from
      0.04 to 3.76 air changes h-1 (ACH), with mean of 0.52 ACH. Median particle
      penetration was 0.89. Emission rates were calculated for each pollutant sampled.
      Using a detailed housing survey and field sampling questionnaires, it was
      possible to evaluate associations between housing characteristics and source
      activities, and pollutant source rates. The data indicate that several predictor
      variables, including mothball storage, air freshner use, and cooking activities,
      are reasonable predictors for emission rates for specific pollutants in the homes
      studied.

PMID- 11235232
TI  - Comparison of field performance of the Andersen N6 single stage and the SAS
      sampler for airborne fungal propagules.
AB  - Comparisons of two common bioaerosol samplers were made after sampling and
      enumeration of airborne fungal propagules in several office structures on a
      university campus in Southern California. Data collected on five occasions
      throughout the year showed that a Surface Air Systems (SAS) high flow portable
      sampler recovered consistently lower levels of colony forming units (cfu) than an
      Andersen N6 single stage impactor. There was no difference statistically between
      the samplers when concentrations of Cladosporium were compared. Compared to the
      Andersen N6, the SAS sampler recovered about half the number of cfu for three
      other fungal categories, i.e. non-sporulating species, Aspergillus and
      Penicillium and others. Differences in sampler efficiencies are discussed in
      terms of effective particle diameters. Counts of culturable airborne fungal
      spores obtained with the SAS sampler should be interpreted with caution when
      genera other than Cladosporium predominate.

PMID- 11235233
TI  - [Health resources and strategies: knowledge and practice of women living in
      poverty areas in Brazil].
AB  - This study presents a reflection on the health resources and strategies used by
      poor Brazilian women and that coexist with "official" medical practices. For this
      qualitative research, the authors applied social representation categories as
      central categories of analysis, which were understood as part of contradictory
      social relations and of the collective history of the groups. The peculiar way by
      which popular segments reaffirm and, at the same time, deny their own
      knowledge/action as a counterpoint to the dominant medical practices is brought
      into focus, beginning from the utilization of a varied set of health resources
      and strategies that include measures such as household-medicine, medical and
      religious practices, self-medication, consultations with "pharmacists" and
      orientation by local health agents.

PMID- 11235234
TI  - [The abused child: review of the literature].
AB  - Assisting abused children may cause discomfort and raise doubts. The present
      literature review, which includes periodicals, books and the Child's and
      Adolescent's Statute, was conducted to serve as reference to professionals and
      researchers involved with the child abuse problem. The authors introduce the
      subject of abuse, present its legal and ethical implications, the difficulties to
      diagnose it, its effects, the necessity to understand and treat its perpetrator
      as well as the role and background of the professionals who assist children
      victimized by abuse. As final considerations, the authors suggest preventive
      steps as well as the improvement of formal systematic research on abused
      children.

PMID- 11235235
TI  - Ecological principles and life quality.

PMID- 11235236
TI  - [Admitting patients: a study in basic health units in the city of Ribeirao Preto,
      Brazil].
AB  - This study was based on the analysis of the relationship established between
      nursing auxiliaries and their clientele in two Basic Health Units at the time of
      clients' reception. The theoretical framework used was that of the "help model",
      whose elements are: attending, responding, personalizing, giving directions,
      becoming involved, exploring, understanding and acting. Four typical cases are
      presented, which show that the relationships are not always personalized, the
      client and the auxiliary do not become involved in the relationship and that
      there is more concern about the development of technical abilities than about
      reception. There are different communication attitudes at the same unit. The
      reception process must be incorporated to the health unit procedures at the same
      time it must transcend the routine character of daily activities.

PMID- 11235237
TI  - [Educational activity during rooming-in: report of the experience of a nurse].
AB  - This study aimed at describing the experience of a group of nursing students as
      to the mother-child binomial while mothers roomed is at a university hospital.
      The main objective was to develop an educational activity related to caring for
      the newborn and the mother during hospital stay, immediately after the birth.
      This is a descriptive study and, in order to develop its activities, the
      participative method and teaching techniques were used. During this learning
      process, we could observe the interest and participation of the parturient women.
      It is the authors' belief that by offering an educational activity during the
      postnatal hospital stay, the level of awareness regarding the relevance of self
      care and of the care for the newborn infant increases, which will result in an
      enhanced quality of life.

PMID- 11235238
TI  - [Impaired communication between nurses and patients' family members].
AB  - This study aims at presenting the analysis of an interaction between a nurse and
      a patient's family member in which impaired communication was observed. The
      interpersonal-relationship theoretical framework was used. The patient was young,
      20 years old, bore a dead fetus and presented various complications. The
      interaction took place with her aunt (stepmother) and as to the structure, it was
      diagnostic, therapeutic and made it possible to establish a proposal of
      continuous assistance. As to content, it was possible to find the points of
      support given by family members and identify new facts so that the nursing team
      could improve the assistance given to the patient.

PMID- 11235239
TI  - [Non-verbal communication; reflections on body language].
AB  - The present study aimed to reflect on the importance of body language through the
      identification of what a graduate nursing group knew about this topic. We
      analyzed the contents of reports from which five categories emerged: concept,
      function, importance, meaning and forms of body language manifestation. The group
      valued body language as a complex way of interpersonal interaction that sometimes
      occurs out of our control and of which we have little conscience. It has the
      function of expressing feelings, emotions and transmitting messages whose
      meanings are influenced by context. Body language knowledge increases our
      professional perception and it is one more instrument to improve nursing
      assistance quality.

PMID- 11235240
TI  - [Cancellation of scheduled surgery at a university hospital: an exploratory
      study].
AB  - In spite of the extensive available literature on surgery patients' preparation
      and on the performance of surgeries, the focus given to the cancellation of the
      surgical act has been quite restricted. This study aims at identifying the number
      of scheduled and cancelled surgeries as well as the services that are mostly
      affected by such cancellations and was carried out in the surgery service of a
      big public university hospital located in the metropolitan area of Fortaleza,
      Ceara. The data were collected through surgery registration books, daily maps of
      surgery schedules and from the files of patients scheduled for surgery from
      September to December, 1996. The gathered data were analyzed quantitatively and
      introduced in charts. The results demonstrate that from the 1,145 surgeries
      programmed in the selected period, 379 (33%) had been cancelled. The mostly
      prejudiced services were General Surgery, Ophthalmology, Head and Neck Surgery,
      Trauma and Orthopedics, Otorhinolaryngology, Nephrology and Renal Transplant, and
      Proctology. Further investigation in this area in order to know the determinant
      causes of surgery cancellation as well as the participation of nursing in the
      study of this problem are necessary.

PMID- 11235241
TI  - [Nursing perceptions in the liver transplantation program of a public hospital in
      Brazil].
AB  - The aim of this study was to uncover the experience lived by nurses working in
      the liver transplant program of a public hospital. In order to understand the
      nurse's experience, a qualitative research based on the "situated-phenomenon
      structure" was designed. The propositions obtained showed that the essence of the
      phenomenon "living the experience of nursing assistance to patients in the liver
      transplant program of a public hospital" was uncovered as living a situation
      which hides needs, difficulties, contradictions, conflicts and satisfaction.

PMID- 11235242
TI  - [Nursing professionals and quality of life: an approach based on the dimensions
      proposed by Flanagan].
AB  - The present qualitative and quantitative study had the purposes to verify the
      meaning of quality of life to nursing professionals using Flanagan's Scale, to
      identify the quality of life dimensions that are most valued by those
      professionals and to explore the relations between the quality of life scores
      obtained by the professionals working at the STD/AIDS unit and at the neonatal
      ICU. The two groups showed similar results with respect to the meanings and the
      most valued dimension of quality of life. The total scores presented a positive
      evaluation of quality of life by the groups, although they showed a difference in
      the level of quality of life experienced by the two nursing teams.

PMID- 11235243
TI  - [Analysis of proxemic factors in the communication with laryngectomized
      patients].
AB  - The present study analyzed the proxemic factors of interactions between health
      professionals and laryngotomized patients in mediate post-surgery. We used the
      non-participant observation technique with pre-established guidelines. Data were
      analyzed according to Hall's theoretical framework. The speakers' sex or color
      did not influence the distance maintained in the interactions; the nursing
      technical care category was predominant; the attitude adopted was compatible with
      the meeting goals; instrumental touch with visual contact was predominant, voice
      tone was adequate to the distances maintained and the authors observed the
      presence of obstacles in some interactions, which demonstrated that communication
      was impaired.

PMID- 11235244
TI  - [Recruitment and selection of human resources in a psychiatric hospital at a
      municipality of Sao Paulo].
AB  - This paper aims at disseminating the experience of recruiting and selecting human
      resources in a psychiatric hospital in the city of Ribeirao Preto, a
      philanthropic institution with one hundred and four beds that assists pharmaco
      dependent patients with mental problems. It presently has eighty-four employees
      and a high staff turnover in different sectors. As trainees, we realized that the
      high turnover impaieds the development of activities at the organization as well
      as prevented a better care delivery to clients. Therefore, we were invited to
      integrate a team that was made responsible for the recruitment and selection of
      human resources for this institution. After these procedures and the respective
      follow-up by those in charge of different sectors, our purpose is to reduce the
      turnover, implement larger institutional engagement and more synchrony among
      employees, reduce expenses and bureaucratic activities related to hiring and
      laying off personnel, reduce operational work and implementing more assisting
      activities in terms of planning, orientation, execution and evaluation.

PMID- 11235245
TI  - [Psychodrama as a pedagogical strategy: experiences in undergraduate teaching of
      women's health services].
AB  - As the result from a discussion by the Grupo de Estudos sobre Saude da Mulher-
      GEM (Group of Studies on Women's Health), psychodrama has been used as a
      pedagogical strategy to develop the topic Female's Conditions and Women's Health.
      Written and oral individual accounts as well as stories constructed in "group
      meetings" were treated by the gender perspective. The dynamics has facilitated
      relationships and self-knowledge, making it possible for day-by-day situations to
      emerge. The reflection between what is lived and what is theoretical has allowed
      the visibility of women's insertion in the public and private sectors as well as
      created situations for the construction of concepts.

PMID- 11235247
TI  - Do the write thing.

PMID- 11235246
TI  - [Comparison of two psychophysical methods for the estimation of the severity of
      illness].
AB  - In this study, 15 diagnoses were selected and evaluated by the methods of
      estimation of magnitudes and estimation of categories. These methods were
      performed by 46 subjects (10 physicians, 20 nurses and 16 psychologists). The
      results show that the non-metric continuum of seriousness of an illness exhibits
      prosthetic characteristics and the variability of estimates is a linear function
      of the magnitude estimation, thus confirming that Ekman's law is also valid for
      non-metric continua.

PMID- 11235248
TI  - Providing spiritual care to patients with cancer.
AB  - Patients with cancer, oncology nurses, and chaplains agree that nurses should
      provide spiritual care, but organizational and professional barriers often exist.
      To overcome these barriers, many nurses need only to complement their
      professional skill sets of problem solving, critical thinking, caring, and
      communication with knowledge of some spiritual-care specifics. This article
      provides basic definitions of religion and spirituality and their relationship as
      well as suggested religiospiritual assessment strategies, standard spiritual
      diagnoses, a pragmatic intervention approach, and documentation recommendations.

PMID- 11235249
TI  - The starving patient: supportive care for people with cancer.
AB  - Unintentional weight loss in people with cancer is associated with decreased
      quality of life and increased mortality. Addressing risk factors that lead to
      weight loss may improve quality of life and prevent cachexia. Specific,
      individualized counseling is the most beneficial and economic intervention for
      nutritional health. Appetite stimulants promote oral intake, and oral supplements
      help to meet the increased need for calories and protein during the course of the
      disease and its treatment. Utilizing the gut for digestion and absorption of food
      maintains the critical functions of the bowel lumen. Tube feeding and parenteral
      nutrition may be indicated for prevention of malnutrition in some disease
      conditions and during certain types of cancer treatment.

PMID- 11235250
TI  - The role of urinary assessment scores in the nursing management of patients
      receiving prostate brachytherapy.
AB  - Nearly all patients experience some degree of urinary irritative or obstructive
      symptoms following brachytherapy for definitive treatment of early-stage prostate
      cancer. The American Urological Association (AUA) Symptom Index is a tool
      developed to measure urinary function and can be incorporated into postoperative
      nursing management. When this questionnaire is administered at regular intervals
      following surgery, the patient's urinary status can be assessed quickly and
      treatment changes made according to symptoms, with resultant improvement in
      comfort levels. The postoperative use of the AUA index is recommended for all
      nurses who care for patients undergoing prostate brachytherapy.

PMID- 11235251
TI  - More on herbs.

PMID- 11235252
TI  - Reporting adverse events associated with herbal products.

PMID- 11235253
TI  - Altered calcium metabolism.

PMID- 11235254
TI  - Myocardial infarction.

PMID- 11235255
TI  - Celecoxib.

PMID- 11235256
TI  - Is this a defining moment in nursing's history?

PMID- 11235257
TI  - Academic research must be relevant to clinicians.

PMID- 11235258
TI  - A practice nurse who endangered patients by not updating her skills.

PMID- 11235259
TI  - Catheterization and urinary tract infections: microbiology.
AB  - Patients with urinary catheters are a substantial proportion of the total patient
      population and catheter care is an important area of nursing practice. Urinary
      tract infection associated with catheterization is known to be the most common
      nosocomial (hospital-acquired) infection. Urinary tract infections can be caused
      by exogenous microorganisms or endogenous faecal or urethral microorganisms. The
      different microorganisms which are responsible for causing urinary tract
      infections have particular characteristics. Many microorganisms form a biofilm, a
      living layer of cells which stick to the surfaces of the catheter and the
      catheter bag. Biofilms not only lead to urinary tract infections, but also they
      are associated with encrustation and catheter blockage. The article considers the
      microorganisms implicated in catheter-associated urinary tract infections and
      aims to develop an increased awareness of the characteristics of different
      pathogens which could lead to enhanced nursing practice and improved patient
      care.

PMID- 11235260
TI  - Conservative treatment of erectile dysfunction. 1: Anatomy/physiology.
AB  - This is the first of a three-part article addressing whether physiotherapy
      involving pelvic floor muscle exercises is efficacious as a first-line treatment
      for erectile dysfunction (ED). In this, the first part of the article, the
      prevalence of ED and associated risk factors are considered after which the
      anatomy of the penis and the physiology of erection are outlined. This provides
      background for the second and third parts of the article which review the
      outcomes of published clinical trials investigating the treatment and prevention
      of ED, and assess the evidence for pelvic floor exercises relieving ED.

PMID- 11235261
TI  - Spiritual healing as adjunct therapy for rheumatoid arthritis.
AB  - At the request of the Confederation of Healing Organizations (CHO) the addition
      of spiritual healing (SH) to conventional therapy has been compared with
      conventional therapy alone in 29 patients with rheumatoid arthritis (RA) using a
      parallel group design. Clinical and biochemical assessments were recorded at
      intervals while subjects received a 6-month course of spiritual healing. Initial
      psychological assessment was also performed. The addition of SH produced no
      significant improvement in any of the relevant clinical or laboratory parameters
      assessed; although groups were not exactly matched at the start, those requesting
      SH had more active disease. Between-group comparison showed only an improvement
      in summated change score (SCS) in favour of SH at week 16, which was lost by week
      24. Individuals displaying the most improvement in pain score or SCS with SH did
      not have a significantly different psychological profile from those patients who
      showed the most deterioration. Although our study was small the results do not
      persuade us to proceed to a larger study for which there would be difficulties in
      study design.

PMID- 11235262
TI  - The relevance of degree-level preparation for community nurses.
AB  - The most recent changes in the preparation of specialist community nurses assume
      that educational improvements automatically increase the skills and knowledge of
      the participants and thus the subsequent quality of care. The rapidly changing
      environment of community healthcare delivery has meant that the possession of
      degree-level qualification is now seen as necessary for flexibility and
      responsiveness to change. However, the philosophy behind this thinking is flawed-
      education does not always reflect the reality of care delivery. Specialist
      community nurses can become further distant allowing them to concentrate on the
      practical application of their newly acquired knowledge.

PMID- 11235263
TI  - Integrated nursing in primary care and analysis of nurses' caseloads.
AB  - Over the past two decades both government and professional bodies have
      continually emphasized the need for an integrated approach to nursing. In
      reality, however, a review of the literature provides little evidence to suggest
      that this has been achieved. What it does show, in fact, are the complexities
      involved in the establishment of such an approach. This study was designed to
      develop an integrated nursing team within Collingham Medical Centre and to
      describe a methodology, which could be replicated by other teams. Studies have
      described the benefits and pitfalls of this integrated working but this is the
      first description of its implementation.

PMID- 11235264
TI  - Supporting family carers using interative multimedia.
AB  - ACTION (Assisting Carers using Telematic Interventions to meet Older persons'
      Needs) is a nursing led Pan-European project (1997-2000). Its primary aim is to
      maintain the autonomy, independence and quality of life of frail older and
      disabled persons and their family carers by the application of telematic
      technology. This article describes the development of two multimedia programmes
      created as part of the ACTION project. Programme 1 'Planning ahead' helps family
      carers and frail older people to think about and plan for the future. Programme 2
      'Break from caring' assists carers and older people to explore the range of
      respite care options available. Both programmes have been developed using a
      multimethod, user-centred approach. Preliminary evaluation data have indicated
      that frail older people and their carers have used the programmes to assist them
      when making difficult decisions such as selecting a nursing home, or exploring
      the use of respite care facilities.

PMID- 11235265
TI  - 3M Tegasorb Thin: a hydrocolloid dressing for chronic wounds.
AB  - Hydrocolloid dressings remain as popular today as when they were first developed
      in the early 1960s (Williams, 1994). The reason for this is that they provide a
      convenient and cost-effective treatment option for those who deal with the
      management of chronic wounds such as pressure sores and leg ulcers. This article
      examines Tegasorb Thin from 3M and shows how it can create the optimal moist
      wound healing environment.

PMID- 11235266
TI  - Self-assessment and the concept of the lifelong learning nurse.
AB  - Nurses appear to be taking an increasing interest in the concepts of lifelong
      learning, learning organization and a learning society. With expanding roles and
      their direct relevance to clinicians' different clinical grades and capacities,
      lifelong learning becomes an essential component in the achievement of clinical
      expertize. Lifelong learning is based on the self-assessment of clinical
      knowledge and competence. However, there are advantages as well as possible
      problems with both peer and self-assessments, and therefore further development
      and research is required.

PMID- 11235267
TI  - Are specialist nurses deskilling general nurses?

PMID- 11235268
TI  - Patients deserve trust not surveillance cameras.

PMID- 11235269
TI  - Nurses must not ignore clients' sexual health needs.

PMID- 11235270
TI  - Nurse who pretended to be a paramedic to treat crash victims.

PMID- 11235271
TI  - The development of a standardized approach to wound care in ICU.
AB  - Reflection and evaluation of wound care administered within the intensive care
      unit where the author is based suggested that an inadequate level of care was
      being provided. No structured approach existed; documentation was poor, with
      practitioners struggling to make decisions on appropriate care. A research study
      supported these reflections, and implied that wound care was delivered on an ad
      hoc basis. Results indicated that this was due to the limited knowledge base of
      practitioners in relation to the wound healing process, and wound management. Few
      staff had ever received any training on this topic and most knowledge was
      acquired through trial and error. No evidence-based approach to wound care was in
      place: thus, care was random and outdated. The results from the research study
      stimulated the development of a comprehensive evidence-based reference guide on
      the topic of wound care, which was designed for use in the clinical setting, and
      has allowed the development of a structured approach to wound care.

PMID- 11235272
TI  - Nursing development units: factors influencing their progress.
AB  - Nursing development units (NDUs) have long been advocated as 'test-beds' for
      pioneering leading-edge practice development. This article reports on the
      findings of a study examining factors influencing the development of NDUs, and,
      more recently, established multidisciplinary practice development units (PDUs).
      Individual and focus group interviews were undertaken with key stakeholders
      involved in six NDUs/PDUs accredited by the University of Leeds. The findings
      from the study highlight a number of internal and external factors that have
      impacted upon the progress made by these units. Importantly, the role of the
      clinical leader, the staffing establishment, organizational infrastructures to
      facilitate dissemination and the nature of the support from managers and medical
      staff have all influenced the success of the NDUs/PDUs. In order to ensure the
      long-term viability of an NDU/PDU it is essential that practice development is
      planned and managed in a systematic and coordinated way with a full appraisal
      undertaken of the human, physical and financial resources necessary to implement
      and disseminate change and that the work of the NDU/PDU is incorporated in the
      trust's strategic plans in order to ensure organizational support.

PMID- 11235273
TI  - Fit for purpose? Promoting the human side of mental health nursing.
AB  - Currently, preparation of mental health (MH) nurses appears to emphasize
      tangible, highly visible skills acquisition. While few credible MH nurses would
      argue with the need for some acquisition of skills during nurse training, it is
      the emphasis on this acquisition of skills at the expense of the development of
      certain other qualities that is questionable. This article argues that the 'human
      side' of MH nursing should not be forgotten or ignored and draws attention to
      evidence of the invisibility of some aspects of MH nursing. It also draws
      attention to how 'human-focused' MH nursing practice may be inhibited by market
      forces, the pressures of economic restraints and the current preoccupation with
      'quick-fixes'. It points out that within the field of psychiatry and MH care,
      there is evidence that some nurses have returned to 1930s neo-Darwinian
      perspectives of the mind. The article suggests that it is unlikely that current
      MH nurse training, with its emphasis on neurobiology and masculine approaches to
      care, adequately prepares MH nurses for ways of working which are described in
      this article as the 'proper focus of nursing'. Additionally, the article points
      out that a view of the development of MH nurse training that includes more
      training in psychotherapeutic approaches to care is not evidence of a fanciful,
      unrealistic or Utopian view of MH nurse preparation.

PMID- 11235275
TI  - Speaking of sex: the need to dispel myths and overcome fears.
AB  - Myths and fears are intimately associated with issues of sex, sexuality and
      sexual health. Many myths and fears, present in both the education and clinical
      settings, prevent health carers from maximizing the potential for wholeness and
      wellness, for both themselves and their clients. In order for nurses, midwives
      and health visitors to take their role in therapeutic communication around the
      sex issues seriously, these myths must be dispelled and the fears overcome. Many
      of the hindrances to communication are shrouded in other people's taboos and
      morals, and hidden within the languages of clinical terminology and silence. This
      leads numerous clinicians and educators to an incommensurate fear of dealing with
      the sexual issues of life. This article argues that this is an example of
      institutionalized erotophobia (fear of sex), which results in a barrier to
      genuine, therapeutic, communication. For the sake of brevity, 'sex' will refer to
      sex, sexuality and sexual health. Likewise, unless a clear distinction is being
      made, 'nurse' will include midwives and health visitors.

PMID- 11235274
TI  - Aerobic capacity, weight gain and psychotropic medication.
AB  - The relationship between physical health and psychological wellbeing is a complex
      one, with each impacting upon the other to one degree or another. Psychiatric
      patients are often reported to be not as physically healthy as their counterparts
      in the general population, with reports of increased weight gain and decreased
      activity. This study of two classifications of psychiatric patients in a high
      security psychiatric establishment was an attempt to ascertain if such a
      relationship existed between physical fitness, psychopathology, weight gain and
      medication levels. Using standardized tests to assess two parameters of health
      related fitness--Harpenden skinfold callipers to estimate percentage body fat
      (BF), and a submaximal cycle ergometer ride for aerobic capacity (VO2 max)-
      results were compared with the general population using the Allied Dunbar
      National Fitness Survey (Sports Council and Health Education Authority, 1992) as
      a reference. The results indicate significant differences in aerobic fitness
      between the two groups (P < 0.01) and such differences could be a cause for
      concern and may constitute a threat to both physiological and mental wellbeing.

PMID- 11235276
TI  - An alternative sectional bedding system: the Nightingale Smart Bed.
AB  - This article describes the Nightingale Smart Bed, a unique three-sectional
      automatic profiling system from Nightingale Care Beds. It is a two-in-one system
      in that it aids in the prevention and management of pressure sores while also
      helping nursing staff to move and handle patients. It maintains patients'
      independence, dignity and comfort and provides an alternative to alternating
      pressure systems.

PMID- 11235277
TI  - Autonomy and clinical practice. 3: Issues of patient consent.
AB  - In this, the last in a three-part series considering how the concepts of
      autonomy, privacy and informed consent are articulated in nursing and the related
      literature, the authors focus on the notion of consent. Definitions of consent
      are considered, as are the legal elements of valid consent. Obtaining a patient's
      consent to treatment has several important functions. This article looks at some
      of these functions, such as safeguarding patient autonomy and encouraging patient
      participation in health care. Finally, a number of the difficulties in obtaining
      an informed consent from patients are considered. Some empirical studies which
      consider patients' understanding of the information and consent process are also
      discussed. From a review of the literature it appears that the issue of informed
      consent is very much tied up with the perceived power struggle between doctors
      and nurses and doctors and their patients.

PMID- 11235279
TI  - "Precarious ordering" higher and deeper.

PMID- 11235278
TI  - Clinical governance: opportunity for nurses?

PMID- 11235280
TI  - Quality of life for Thai women with diabetes.
AB  - Based on the data obtained from a larger exploratory descriptive study, life
      quality of 57 Thai women with diabetes was explored. Eighteen women from 57
      original participants were interviewed regarding life characteristics that are
      important to their life quality. Thai women with diabetes perceived moderate
      satisfaction with their life at present. The age at onset of diabetes
      significantly correlated (r = -.30, p < .05) with life satisfaction scores of
      women. Life characteristics that were important to their life quality included
      five categories: family, living conditions, success in life, health, and personal
      faith. The findings add to the knowledge base about life quality of women with
      diabetes in Thailand and to the understanding of the cultural specificity of
      human experiences and the quality of life concept in general.

PMID- 11235281
TI  - Transforming the exhausting to energizing process of being a good parent in the
      face of cancer.
AB  - The aim in this study was to gain a deeper understanding of the interaction
      between women who have been treated for breast cancer and their children. The
      focus was on how they deal with being a mother at the same time attending to
      their own needs. The main strategies of the grounded theory method were used to
      conceptualize the interactive process involved. Nine women, with children aged 4
      to 23, living at home at the time of diagnosis, were interviewed. By the process
      of constant comparative analysis, the main theme that seemed to capture how the
      lives of these women had changed was transforming the exhausting-to-energizing
      process in being a good parent in the face of cancer. This theme is related to
      Meleis's concept of health-illness transition. The findings here indicate the
      need for family counseling, with special attention paid to the single parent with
      cancer.

PMID- 11235282
TI  - Persisting while wanting to change: women's lived experiences.
AB  - This article presents an inquiry into a common lived experience, which the author
      named persisting while wanting to change to signify the struggle of trying to
      change health patterns. Parse's phenomenological-hermeneutic methodology was used
      to investigate the phenomenon, as it is lived by women in an abusive
      relationship. Through dialogical engagement with the researcher, eight women
      described their experiences of persisting while wanting to change. The generated
      structure and central finding contained three core concepts: wavering in abiding
      with the burdensome-cherished, engaging-distancing with ameliorating intentions,
      and anticipating the possibilities of the new. The core concepts are illustrated
      with excerpts from the dialogues and are discussed in relation to Parse's human
      becoming theory and related literature. Findings are consistent with those of
      other studies in which leaving an abusive relationship was described as a
      process. Implications for practice and further research also are discussed.

PMID- 11235283
TI  - Young western women's experiences of menarche and menstruation.
AB  - A qualitative approach was used to examine young women's experiences of menarche
      and menstruation that were included in personal stories of growing up sexually.
      The personal experiences were examined by cross-case analysis to learn more about
      the narrators' attitudes toward menarche and their menstrual-related education.
      This was a secondary analysis using data collected for a study of common themes
      in the stories gathered in a 1998 study by Beausang. The data came from 332
      stories written by students taking a sexuality course in a Midwestern community
      college. Of 227 stories written by women, 85 stories included menstrual
      experiences. Eleven narrators described menarche as a positive experience. In 10
      of these stories, the mother was the primary teacher. The two most frequently
      identified sources of information by narrators were mothers and schoolteachers,
      with most narrators having a primarily negative view of their menstrual education
      regardless of the source. Problems with menstrual-related education were
      described as perceptions of unwillingness by teachers to discuss menstruation,
      time limits for education, unclear instruction leading to misconceptions, and the
      presence of peers in group learning situations that lead to embarrassment.

PMID- 11235284
TI  - Women's health custom made: building on the 40 days postpartum for Arab women.
AB  - The 40-day postpartum period is characterised in the Middle East and elsewhere by
      an observance of seclusion, congratulatory visiting, the reciprocal exchange of
      gifts and money, and a special diet. Based on primary data from in-depth
      interviews among the Negev Bedouin in Israel, health enhancing practices are
      reviewed. The data are a subset from a larger study carried out in this setting.
      Often postnatal checkups, family planning counselling, and immunization services
      may not be routinely available or used. It is argued that these health services
      could be provided at the end of the 40-day period for mother and child, as in a
      pilot study in Tunisia some years ago. Health service provision would thus build
      on the health enhancing practices of the 40-day period.

PMID- 11235285
TI  - Midlife women's attributions for their sexual response changes.
AB  - This study focused on the sexual response changes of 280 mostly White, married,
      highly educated midlife women and on the attributions they made for these
      changes. In a U.S. sample of women participating in the Midlife Women's Health
      Survey (MWHS), women whose sexual response had changed in the past year (40%)
      reported more decrements than increases in sexual response. When asked how they
      accounted for these changes, women referred most often to the physical and
      emotional changes of menopause and to life circumstances, and less often to their
      relationships with their partners. The attributions showed a distinct pattern:
      Most of the decrements were explained by physical events related to menopause,
      whereas most of the increases were explained by life circumstances. These
      findings are discussed in terms of a need for studying women's sexuality from a
      biopsychosocial perspective.

PMID- 11235286
TI  - The development of an effective tissue viability service.
AB  - Wound management and the prevention and treatment of pressure ulcers is
      recognized as a major quality issue (Department of Health (DoH), 1993). However,
      there remains a number of NHS trusts who operate without a formal tissue
      viability service (TVS) (Dealey, 1994). The aim of this article is to assist
      those wishing to develop such a service by describing how the authors' TVS became
      established and how it has developed during the subsequent 5 years (Smith, 1996).
      It is anticipated that this information will provide a framework for
      practitioners who want to develop this specialty within their own trust.
      Traditionally, the detection and treatment of pressure ulcers has been the role
      of nursing staff. However, it is now recognized that this responsibility lies
      with many members of the multidisciplinary team, the members of which provide the
      foundation of an effective TVS (Smith, 1993).

PMID- 11235287
TI  - Sharing information and clinical experiences.

PMID- 11235288
TI  - Above the knee amputation wound which dehisced following surgery.
AB  - This case study describes the wound care of Mrs A, a female patient whose above
      the knee amputation wound dehisced after surgery. The management of this wound
      was complex and challenging and required that many members of the
      multidisciplinary team to work together to achieve a satisfactory outcome.

PMID- 11235289
TI  - A case study in evidence-based wound management.
AB  - On the first of July 1998, Frank Dobson, the then Secretary of State for Health,
      revealed the consultation document 'A First Class Service' (Department of Health
      (DoH), 1998). This article describes a wound management case study which showed
      how a first class service was provided for a patient with very severe pressure
      ulcers and complex medical problems. A multiprofessional approach to her complex
      and challenging problems was maintained. Evidence-based guidelines for the
      prevention and management of pressure damage were followed, supported by modern
      researched-based wound management and pressure relief. In addition, risk
      management strategies were observed, and provided the basis for planning and
      evaluating her individualized care.

PMID- 11235291
TI  - Investigating the value of pressure sore prevention.

PMID- 11235290
TI  - The improvement of wound care provision in Spain.

PMID- 11235292
TI  - Individuals must not take the blame for the system.

PMID- 11235293
TI  - Protecting the public through self-regulation.

PMID- 11235294
TI  - ITU nurse found guilty of causing grievous bodily harm.

PMID- 11235295
TI  - Leukotrienes: new therapies and their influence on asthma.
AB  - Leukotriene receptor antagonists (LTRAs) are new therapies in asthma management
      which act to block the naturally occurring leukotrienes and improve lung
      function. It is clear from past research that many asthmatics dislike taking both
      oral and inhaled steroids and may probably welcome these new drugs simply because
      they are not steroid preparations. The oral route of LTRAs may be helpful for
      particular groups of patients, although LTRAs will not be suitable for all
      asthmatics. Their use so far has been largely as 'add-on' therapies for mild-to
      moderate asthma with results that are promising in some patients but have been
      disappointing in others. Fewer side-effects may well improve medication
      compliance which has caused both unnecessary morbidity and has been linked to
      mortality in the past.

PMID- 11235296
TI  - Conservative treatment of erectile dysfunction. 2: Clinical trials.
AB  - This is the second of a three-part paper addressing whether physiotherapy
      involving pelvic floor muscle exercises (PFMEs) is efficacious as a first-line
      treatment for erectile dysfunction (ED). The first part (Vol 9(11): 691-4)
      highlighted the prevalence of ED, associated risk factors, the anatomy of the
      penis and the physiology of erection. This part concentrates on the computer
      aided and manual search for published clinical trials investigating the treatment
      and prevention of ED. The methodological quality of the trials was assessed using
      criteria based on generally accepted principles of interventional research. The
      literature search revealed 14 trials which met the broad inclusion criteria. Of
      these, eight trials used PFMEs with or without biofeedback or electrical
      stimulation.

PMID- 11235297
TI  - Quality and marketing issues in nursing education.
AB  - Two important issues in nursing education are quality and marketing. These issues
      both complement and support each other. The aim of this article is to highlight
      the concepts of quality and marketing as a valuable partnership in nursing
      education, a partnership that is capable of improving the quality of education
      provision and potentially of increasing student numbers. Major themes include an
      analysis of the reluctance by institutions to implement marketing strategies, the
      image of the institution, and customer satisfaction. The article concludes by
      suggesting that nurse educators need to know who their customers are, who they
      could be, and what those customers want and need, in order to run successful and
      valued courses.

PMID- 11235298
TI  - Assessment of eating and drinking in a child with a gastrostomy.
AB  - During periods of short-term (respite) care a full and comprehensive assessment
      is essential if the wellbeing of a child with complex healthcare needs is to be
      maintained or advanced in the parents' absence. Eating and drinking is just one
      component of an holistic assessment carried out at The Children's Trust in
      Tadworth. There is an increasing use of different gastrostomy devices, feed
      products and regimes to meet the individual needs of a child and his/her family.
      The assessment tool used reflects the tension of using an holistic approach while
      trying to unravel or breakdown complex care needs into manageable 'chunks' for
      documentation purposes. The role of the parents is pivotal in ensuring the
      success of the assessment process.

PMID- 11235299
TI  - Understanding children with autism: exploding the myths.
AB  - The incidence of autism is increasing in both the USA and in Britain. There is
      still controversy over what causes autism and even greater controversy over
      selecting a preferred method of intervention and support (as there is no
      treatment for autism). Although there is now a general consensus that individuals
      may have a genetic predisposition to develop autism, it is also acknowledged that
      this may be off set by a range of environmental and/or biological factors. The
      understanding of the causation of autism is now considered in much the same way
      as we understand cerebral palsy, in that there can be a range of different
      reasons for causation and prevalence. This article, the first of two parts, will
      explore how an awareness and understanding of autism can enable nurses working
      with children with autism to provide more child-centred nursing care based on
      fact as opposed to stereotype and mythology surrounding autism. The second part
      will concentrate on adults with autism.

PMID- 11235300
TI  - Information booklets for patients with major bowel resection.
AB  - This article highlights the importance of providing information that meets the
      needs of surgical patients. Focus group interviews were used to ask patients who
      had undergone major bowel surgery what information they felt was required to help
      prepare someone for this experience. A group of patients who had recently had
      bowel surgery were interviewed by two facilitators. This technique allowed the
      participants to identify and verify the issues of concern and to originate new
      ideas through group discussion. The participants identified many issues that
      would not have been considered by the authors, issues that were used to form the
      content of three information booklets for patients having bowel surgery.

PMID- 11235301
TI  - The utilization of the healthcare assistant role in intensive care.
AB  - The increasing role of healthcare assistants (HCAs) in intensive care in relation
      to patient monitoring has raised concerns among some clinical managers,
      particularly where such roles are not underpinned by a sound knowledge base and
      critical reasoning ability. This article describes a study which was undertaken
      in an attempt to identify how HCAs are currently utilized within the general
      intensive care environment. The results show a wide variation between units in
      relation to the activities undertaken by HCAs, their training and the levels of
      remuneration. This article seeks to open up the debate as to whether or not
      nurses should be challenging the nursing care that is now delivered by non-nurses
      and makes recommendations for the way forward in this area.

PMID- 11235302
TI  - Doctors are not gods: a few just think they are.

PMID- 11235303
TI  - A college-based nursing updating course.

PMID- 11235304
TI  - Competence and British nursing: a view from history.
AB  - In the light of current political and professional debate in the United Kingdom
      concerning preparing nurses for competence, this paper takes an historical
      perspective, and considers how nursing competence was defined historically
      through an analysis of statutory syllabuses and nursing textbooks 1874-1977.
      Competence was perceived by nursing textbook writers to have four facets.
      Firstly, it involved the moral character of the nurse; secondly, it required
      technical knowledge, practical skill and procedure; thirdly, it depended on the
      role of the ward sister; and fourthly, it relied on the professional etiquette of
      right relationships. The analysis shows that the traditional system of nursing
      competence presumed a clearly defined purpose: the production of the bedside
      nurse, whose function was to care for the sick person. This raises a fundamental
      question for nursing today: what is the purpose of the modern nurse?

PMID- 11235305
TI  - Assessment of graduates and diplomates in practice in the UK--are we measuring
      the same level of competence?
AB  - With the recent proliferation in nursing degree programmes over the last 10 years
      and a suggestion that nursing moves towards an all-graduate profession, the
      profession as well as the consumer needs to be sure that they are getting 'value
      added' with this 'higher level' practitioner. This paper revisits the debate on
      the meaning of competence in relation to fitness for practice. In particular it
      examines the expectations of the profession of newly registered practitioners at
      both diploma and degree levels of practice. It questions whether there is a
      difference in their level of competence at point of registration and whether it
      is possible to measure it. The paper presents a reflective approach to promoting
      ideas already emerging from the literature in relation to this measurement. It
      suggests a more effective use of students' portfolios of evidence against stated
      learning outcomes as well as their specific achievements in a range of
      transferable skills. A partnership approach between student,
      practitioner/assessor and academic could usefully share responsibilities of the
      assessment of competence and ultimately empower the individual for their life
      long learning.

PMID- 11235306
TI  - Information point: National Vocational Qualifications (NVQ).

PMID- 11235307
TI  - Competency for nursing practice.
AB  - This article discusses the report of the United Kingdom Central Council for
      Nursing, Midwifery and Health Visiting (UKCC) Commission that was published in
      1999. Problems identified with the previous Project 2000 model of diploma-level
      nursing programmes are identified, including student criticisms of placement
      arrangements and the existence of both theory-practice and practice-theory gaps.
      The UKCC Commission's recommendations for curricular revision are discussed,
      particularly in relation to clinical competence and how this should be defined
      and measured. The implications for who should supervise and assess students in
      clinical practice are also explored. The importance of preparing and assessing
      students for holistic individualized care which respects patients' own beliefs,
      values and culture is emphasized.

PMID- 11235308
TI  - Paying Peter and Paul: reconciling concepts of expertise with competency for a
      clinical career structure.
AB  - This paper identifies current UK policy for exploring both competence and
      expertise. It is argued that the purpose of assessing competence and expertise is
      relevant in deciding the approaches used. Different perspectives about
      competence, specifically those that have arisen in the United States and the
      United Kingdom, are considered in relation to how competencies may be developed
      and assessed. The different terms used in discussion about competency are also
      discussed. From the literature, criteria for selecting experts in nursing, the
      attributes of expertise and enabling factors are presented in relation to how
      expertise in practice may be judged. The pilot recognition process and
      development of evidence for the Royal College of Nursing's Expert Practice
      Project, together with its facilitation through critical companionship, are
      described. It is concluded that the processes necessary for demonstrating
      expertise in practice are consistent with the recognition that the attributes of
      expertise are interdependent, complex and situational. Critical companionship
      provides a mechanism which is primarily developmental and supportive, but focuses
      on practice development and practitioners' effectiveness and can result in the
      development of evidence for a range of different purposes such as demonstrating
      expertise, as well as practice development, service development and career
      progression.

PMID- 11235309
TI  - Work-based learning as a means of developing and assessing nursing competence.
AB  - Work-Based Learning is the bringing together of self-knowledge, expertise at work
      and formal knowledge. It takes a structured and learner-managed approach to
      maximizing opportunities for learning and professional development in the
      workplace. The development and assessment of nursing competence can be
      facilitated through Work-Based Learning, although this may require pedagogic and
      structural changes within nurse education. There are a number of conditions which
      must accompany effective participative learning, and these are discussed in the
      paper in relation to examples of nursing programmes. This method of learning and
      assessment has potential to bridge the gap between theory and practice, and as
      such it can only be achieved through commitment and partnership between the
      individual practitioner, clinical services and universities.

PMID- 11235310
TI  - A comparison of the nursing competence of graduates and diplomates from UK
      nursing programmes.
AB  - This paper reviews the literature on nursing competence measurement and reports
      the results of a comparative quantitative study of the competencies of Project
      2000 diplomates and BA (Hons) Adult Nursing graduates from two UK nursing
      programmes. The findings reveal that graduates appear to overcome any initial
      limitations and become more competent than the diplomates in certain areas.
      Attention to social awareness and participation is necessary in both pre
      registration programmes, whilst greater attention could be given to graduates'
      leadership and management development. Diplomates need support in their
      professional development if they are to achieve the same level of competence as
      graduates during the first post-qualifying year. There are implications for the
      level of support afforded to qualifying nurses in their first staff positions;
      preceptorship programmes could be an important means of assisting newly qualified
      staff to gain confidence. More research on nurse competencies with larger samples
      drawn from programmes across the UK is needed.

PMID- 11235311
TI  - Information point: analysis of variance (ANOVA).

PMID- 11235312
TI  - Information point: Wilks' lambda.

PMID- 11235313
TI  - A formula for diversity: a review of critical care curricula.
AB  - This paper is based on a documentary analysis and literature review of critical
      care nursing commissioned by the English National Board for Nursing, Midwifery
      and Health Visiting. Five critical care programmes were included in the analysis:
      ENB 100, 124, 199, 176/183, and 415. In total, 105 curricula were reviewed from
      30 institutions. Data were extracted and analysed using an adapted grounded
      theory approach. The documentary analysis was supplemented by two telephone
      surveys with lecturers (n = 84) and clinical managers (n = 81). There was great
      diversity in the programmes in terms of the academic level at which the courses
      were set, module configuration, approaches to practice assessment and the amount
      of student effort for the same professional award. Diversity arose because of
      different university module formulae, different methods to differentiate level 2
      and level 3 practice, different views about the purpose of the course, and an
      attempt to make the programmes increasingly flexible to accommodate a
      heterogeneous student population. Documentary analysis has its limitations, and
      although the research team were able to check out issues with lecturers
      throughout the analysis, they were unable to capture the lived experience of the
      curriculum. A second study has been commissioned by the ENB to explore how these
      issues influence practice.

PMID- 11235314
TI  - Technological competence as a fundamental structure of learning in critical care
      nursing: a phenomenological study.
AB  - Post-registration education programmes are frequently informed by nationally
      agreed curriculum frameworks. Although these aim to promote comparability between
      similarly focused clinical courses, inconsistencies have recently been identified
      across a range of critical care curricula. This suggests that broad-based
      frameworks may be insufficiently sensitive to local learning needs. This study
      was concerned with the extent to which the curriculum met the learning needs of
      10 post-registration critical care students and, in particular, aimed to explore
      the meaning of learning to the students themselves. The study revealed
      technological competence to be a necessary foundation to the development of
      clinical practice and this is discussed from a philosophical perspective which
      allows the nature of contemporary nursing practice to be reconceptualized. It is
      argued that curriculum development for clinically based, post-registration
      courses can be constructively informed by local consultation and that
      phenomenological study can complement more traditional approaches often relied
      upon in educational research.

PMID- 11235315
TI  - Updating cardiopulmonary resuscitation skills: a study to examine the efficacy of
      self-instruction on nurses' competence.
AB  - Nurses' competence in cardiopulmonary resuscitation (CPR) has been shown to be
      consistently poor over the past decade. Studies have suggested that CPR teaching
      methods need to be evaluated and refined in order to improve practice. Self
      instruction has been suggested as one alternative to formal retraining
      programmes, but has not been evaluated with respect to nurses in the UK. A quasi
      experimental design utilizing random allocation of matched subjects to one
      experimental and two control groups was adopted with a sample of 20 undergraduate
      nursing students. The subjects' CPR ability was assessed concurrently using a
      resuscitation manikin and an observational checklist. Subjects undertaking self
      instruction produced significantly (P < 0.05) higher ability scores than those
      who did not participate in retraining. The time spent in self-instruction was
      evaluated positively by the students. The results are discussed in the light of
      previous research and current recommendations for regular CPR updating by all
      clinical nurses.

PMID- 11235316
TI  - Education and training towards competency for cardiac rehabilitation nurses in
      the United Kingdom.
AB  - The development of cardiac rehabilitation in the UK, the evolution of the nursing
      role as a speciality, and the nursing role within the multidisciplinary team are
      briefly outlined. The potential impact of different professional backgrounds on
      the effectiveness of patient care is discussed, with particular reference to the
      differences between acute cardiac care and rehabilitation. Issues of professional
      competency are discussed, and core competencies for cardiac rehabilitation as
      specified by various professional associations are described. Current
      opportunities for preparation for practice in this field in the UK are outlined.
      Conclusions point towards the need for clearly specified competencies and an
      accredited programme of education and training to meet proposed standards for the
      management and rehabilitation of coronary heart disease (CHD) in the UK.

PMID- 11235317
TI  - Medical and surgical nurses' perceptions of their level of competence and
      educational needs in caring for patients with cancer.
AB  - Recent proposals recommend that cancer patients are cared for, as much as
      possible, in specialist cancer units and centres. However, a large number of
      these patients will still be admitted to medical and surgical wards of general
      hospitals at one time or other. Yet little is known about the knowledge and
      skills of nurses dealing with this group of patients. A survey design was used to
      assess the self-reported level of competence, in a number of activities relating
      to their work with cancer patients, among medical and surgical nurses (n = 106)
      in a district general hospital in Northern Ireland. It also aimed to identify
      their self-reported educational needs in caring for this group of patients.
      Results showed that these nurses cared for people with a range of cancers. While
      they reported an above-moderate level of competence, they also rated their level
      of competence higher in physical than in psychosocial care. Among their self
      perceived educational needs were more knowledge, and skills in psychosocial care,
      communication, dealing with side-effects of treatment and pain management.

PMID- 11235318
TI  - Collaboration in cancer nursing practice.
AB  - Although nursing represents around half of Europe's healthcare budgets, its
      impact is seldom evaluated. However, given the current era of cost-containment,
      nursing must prove the value of its clinical effectiveness. Through European
      collaboration, the WISECARE project is working towards identifying the unique
      contribution of cancer nursing. This paper will explain the rationale and goals
      of the WISECARE project and demonstrate the collaborative processes involved
      within such a project. The latest results of the project will be presented to
      prove the value of collaboration in ensuring the development of European
      standards of nursing care.

PMID- 11235319
TI  - Developing occupational standards: a learning disabilities project.
AB  - Occupational standards are often seen as cumbersome and inappropriate to a
      vocational curriculum such as nursing. However, the term fitness for practice is
      once more being used to focus the minds of educationalists and practitioners in
      healthcare delivery on the goal in preparing practitioners for the future. The
      project reported here was guided jointly by staff from a higher education
      institution and an NHS trust and involved practitioners in designing occupational
      standards with a view to using them in practice and incorporating them into the
      preregistration curriculum. The pivotal structure in this process was the focus
      group which, with tenacity and commitment, designed, developed and structured
      standards which were realistic and relevant to healthcare delivery.

PMID- 11235320
TI  - Recognition of depression by staff in nursing and residential homes.
AB  - Newly admitted residents in long-term care facilities are particularly vulnerable
      to depression and the early recognition and treatment of depression is therefore
      crucial around the time of admission to a home. Staff from 30 nursing and
      residential homes were asked to assess newly admitted residents for depression
      using HoNOS 65+ and their responses were compared with residents' scores on the
      Geriatric Depression Scale (GDS-15). The findings indicated low levels of
      recognition by staff, with rates ranging from 15% to 27% of those identified as
      depressed, depending on the definition of depression used. There was no
      statistically significant difference in the rate of recognition between nursing
      staff and other care staff. A staff survey conducted in the 30 study homes
      indicated that fewer than 2% had received specific in-service training on
      depression in older people. The findings suggest that more needs to be done to
      raise staff awareness of depression in residents of nursing and residential
      homes, particularly in newly admitted residents.

PMID- 11235321
TI  - A question of competence? Re-evaluating the roles of the nursing auxiliary and
      health care assistant in the NHS.
AB  - This article draws from the first national sample survey evidence and detailed
      case studies of both the long-standing grade of Nursing Auxiliary/Assistant and
      of the new grade of 'Health Care Assistant/Support Worker' in the NHS. It argues
      for a fundamental re-evaluation of the real competencies of non-registered
      caregivers, and of their potential to progress into registered nurse training.
      The study demonstrates their real maturity, experience, competencies, roles and
      responsibilities, along with the extent to which they perceive themselves as
      'substituting' for registered nursing staff. It is shown that many have been
      blocked from entering registered nurse training due to domestic and financial
      constraints. The rise of NVQ accreditation has now provided both the potential
      for a formal recognition of their experimental learning and also the means by
      which they might progress into registered nurse training or even along parallel-
      and more practice-orientated--lines. It is argued that registered nurses should
      welcome a more fluid and progressive role for these team members, since, failing
      such a welcome, managers will otherwise continue to 'undercut' registered staff
      with their 'cheaper' non-registered caregiving colleagues.

PMID- 11235322
TI  - The development of clinical competencies for use on a paediatric oncology nursing
      course using a nominal group technique.
AB  - This paper outlines the development of a competency model to be used to assess
      clinical competence during a post-registration specialist course. A nominal group
      technique was used to gather data about the detailed practice of paediatric
      oncology nurses. The nominal group technique was chosen to achieve consultation
      and consensus with a professional group. The six steps from undertaking the
      nominal group technique to implementation are described in detail. Some
      reflections on the use of competency statements are offered.

PMID- 11235323
TI  - Developing a nurse-led cystoscopy service.

PMID- 11235324
TI  - Manual handling in the perioperative environment.

PMID- 11235325
TI  - Threats and opportunities facing the theatre nurse.

PMID- 11235326
TI  - Making a difference. Nursing and midwifery education.

PMID- 11235327
TI  - The air we breathe. Audit to evaluate how healthy the working environment is in
      recovery.

PMID- 11235328
TI  - Anaesthetic drugs.

PMID- 11235329
TI  - The 'blind night watchman'.

PMID- 11235330
TI  - Short and simple wins race.

PMID- 11235331
TI  - NPs as expert witnesses.

PMID- 11235332
TI  - Herbal treatments for menopause. Black cohosh, soy and micronized progesterone.

PMID- 11235333
TI  - Sins of the sun. Tools for skin cancer prevention and early detection.

PMID- 11235334
TI  - Sickle cell disease in children. Providing comprehensive care for a chronic
      condition.

PMID- 11235335
TI  - Managing HIV. Understanding the pharmacodynamics.

PMID- 11235336
TI  - Recognition, research, reimbursement. Ensuring business survival into the 21st
      century.

PMID- 11235337
TI  - Media relations 101. A crash course for NPs.

PMID- 11235338
TI  - Put it in writing. Elements of a good contract.

PMID- 11235339
TI  - In the trenches of private practice. One NP's struggle.

PMID- 11235340
TI  - Hypertension in patients with diabetes. Making the best treatment decisions.

PMID- 11235341
TI  - Multicultural care. Meeting the challenge.

PMID- 11235342
TI  - Acute pyelonephritis. A case discussion of primary care issues.

PMID- 11235343
TI  - The latest choice in wound closure. When and how to use Dermabond.

PMID- 11235344
TI  - Channel hopping.

PMID- 11235346
TI  - Follow your leader.

PMID- 11235345
TI  - Cut it out to quit & win.

PMID- 11235347
TI  - Separating the sexes.

PMID- 11235348
TI  - Devolving knowledge.

PMID- 11235349
TI  - Depressing reactions.

PMID- 11235350
TI  - Private boundaries.

PMID- 11235351
TI  - Attractive force of nursing.

PMID- 11235352
TI  - Gender issues in nursing.

PMID- 11235353
TI  - The effectiveness of nursing in stroke units.
AB  - BACKGROUND: Richard Warner examines how nurses might contribute to the
      effectiveness of organised stroke care by linking the theoretical basis of
      nursing with outcomes that could be more meaningful to the stroke survivor.
      CONCLUSION: Although research shows that specialised stroke units are effective
      in limiting morbidity and mortality, and in promoting functional ability, the
      various care roles of the multidisciplinary team are not clear.

PMID- 11235354
TI  - Philosophical implications of the use of advance statements (living wills).
AB  - The growing prevalence of advance statements represents an important shift away
      from paternalistic care. Patients' willingness to begin to take more personal
      responsibility for their own health, and demand for a collaborative partnership
      with healthcare professionals, is evidence of a new paradigm. In this article,
      the concepts of rights, values and personhood are used to analyse the ethical
      issues raised by advance statements.

PMID- 11235355
TI  - Magnet nursing services recognition programme.

PMID- 11235356
TI  - Peripheral vascular disease.
AB  - This article discusses peripheral vascular disease and its associated risk
      factors. It outlines clinical patient assessment, medical interventions and the
      role of the nurse in secondary prevention.

PMID- 11235357
TI  - Injection site safety.
AB  - Practice profiles are reflective pieces written by nurses in practice and based
      on continuing professional development articles. This week Nicola Soanes
      discusses injection sites. Article no. 498. Workman B (1999) Safe injection
      techniques.

PMID- 11235358
TI  - Getting the experts together.

PMID- 11235359
TI  - Skin deep.

PMID- 11235360
TI  - Beat the clock.

PMID- 11235361
TI  - . . . now it's 'our' patient.

PMID- 11235363
TI  - Lottery of life.

PMID- 11235364
TI  - Here's one I donated earlier.

PMID- 11235362
TI  - Open your eyes.

PMID- 11235365
TI  - A blow for accuracy.

PMID- 11235366
TI  - Where there's a will.

PMID- 11235367
TI  - Preventing heroin overdose.

PMID- 11235368
TI  - Witnessed resuscitation: good practice or not?
AB  - Should relatives be given the choice to witness the resuscitation of a family
      member? From the available literature, three main topic areas emerge: research
      studies that allow witnessed resuscitation, the effects on relatives of witnessed
      resuscitation, and A&E staff attitudes towards witnessed resuscitation. There is
      abundant literature on the positive effects for relatives of witnessing the
      attempted resuscitation of a loved-one, the main benefit being that the grieving
      process was made easier. However, staff attitudes are mixed, making witnessed
      resuscitation a controversial topic.

PMID- 11235369
TI  - Changing practice: are memes the answer?
AB  - Nurses are insistent that they have a great deal more to offer than being merely
      doctors handmaidens. This article examines how nursing education and practice can
      be changed by increasing our knowledge of 'memes'--the cultural equivalent of
      genes--and the ways traditional beliefs are passed down to generations of nurses.

PMID- 11235370
TI  - Resource management: making a difference in mental health.
AB  - Bed management problems exist throughout the NHS but are not usually highlighted
      in mental health. Therefore, a project set up in Dewsbury NHS Trust aimed to
      raise awareness and lead to an examination of, and improvements in, resource
      management.

PMID- 11235372
TI  - Care of the patient with oesophageal varices.
AB  - Practice profiles are reflective pieces written by nurses in practice and based
      on continuing professional development articles. This week Suzanne Hudson
      discusses Oesopahgeal varices. CPD article NS 17. McArdle J (1999) Understanding
      oesophageal varices.

PMID- 11235371
TI  - Teaching and promoting testicular self-examination.
AB  - Testicular cancer is the commonest malignancy of young men, but it also has a
      high cure rate. This article discusses the teaching and promotion of testicular
      self-examination as a technique for early detection of the disease.

PMID- 11235373
TI  - Advantages of home life.

PMID- 11235374
TI  - Continence assessment.

PMID- 11235375
TI  - Should nurses have the right to opt out of ECT treatment?

PMID- 11235376
TI  - A creche landing for generation X.

PMID- 11235377
TI  - If wimps ruled the world....

PMID- 11235378
TI  - Truth? Who needs it?

PMID- 11235380
TI  - The government must get the balance right in its recruitment drive.

PMID- 11235379
TI  - The last resort.

PMID- 11235381
TI  - Patient-centred care. Power dressing.

PMID- 11235382
TI  - Can agency nurses be held accountable for bad practice?

PMID- 11235383
TI  - Killing smoke.

PMID- 11235384
TI  - Close encounters of the slurred kind.

PMID- 11235385
TI  - What price confidentiality?

PMID- 11235386
TI  - Preventing the uptake of smoking in young people.

PMID- 11235387
TI  - Freedom to practise: the doctor-nurse relationship.

PMID- 11235389
TI  - Surgery and acute care following hip fracture.

PMID- 11235388
TI  - Managing a patient with an infected pacemaker site.

PMID- 11235390
TI  - Roles and responsibilities.

PMID- 11235391
TI  - Making your relationship work.

PMID- 11235392
TI  - Intravenous infusions: problem-solving.

PMID- 11235393
TI  - Facing cancer hand-in-hand.

PMID- 11235394
TI  - Can nurse leaders lead if they don't nurse?

PMID- 11235395
TI  - Public image limited.

PMID- 11235396
TI  - A health debate dominated by the white-coat brigade.

PMID- 11235397
TI  - Write it down, for everyone's sake.

PMID- 11235398
TI  - Nursing: a family favourite.

PMID- 11235399
TI  - With the issue of the role of HCAs comes the question of skill mix.

PMID- 11235400
TI  - What should I do about an abusive patient?

PMID- 11235401
TI  - A nursing home of your own.

PMID- 11235402
TI  - Babies who cry persistently: the scale of the problem.

PMID- 11235403
TI  - An art therapy group in palliative cancer care.

PMID- 11235404
TI  - Abnormal scar formation in wound healing.

PMID- 11235405
TI  - Rehabilitation at home following hip fracture.

PMID- 11235406
TI  - Evaluating clinical supervision.

PMID- 11235407
TI  - Evaluating supervision: can it really be done?

PMID- 11235409
TI  - Variety is the spice of life.

PMID- 11235408
TI  - Intravenous infusions: calculating rates.

PMID- 11235410
TI  - Practice development revisited: clarifying the concept.

PMID- 11235411
TI  - Collaboration works: the experience of developing a high dependency-nursing
      course.
AB  - Staff in an NHS trust and a university faculty worked collaboratively to develop
      a specific course for nurses working in high dependency areas. Initial evaluation
      suggested that there has been a positive impact on practice in that nurses who
      had completed the course were willing to share new knowledge and undertake
      teaching; management of patient care had become more effective; and the nurses
      were more willing to care for sicker patients. Nurses had also developed critical
      and reflective skills and were keen to review and develop practices through
      activities such as audit. This project has highlighted not only the need for
      practice based experience in caring for the critically/acutely ill patient but
      also the need for formal educational input from expert staff. It is concluded
      that advances in practice must be supported by appropriate education and
      training, and organisations need to work collaboratively in order to respond to
      the needs of staff and patients.

PMID- 11235412
TI  - The Glasgow Coma Scale in intensive care: a study.
AB  - This study reviewed neurological assessment and therapeutic intervention records
      of adult, intubated, sedated and ventilated patients who had sustained a severe
      cerebral insult. The purpose of the study was to determine whether the Glasgow
      Coma Scale detected neurological change in the ventilated, sedated patient. In
      addition the study aimed to establish whether changes to therapeutic intervention
      took place in response to an alteration in Glasgow Coma Scale parameters. A
      retrospective analysis of patient observation records was conducted and
      descriptive statistics presented. The study found that the Glasgow Coma Scale did
      not predict or correlate with a sustained rise in intracranial perfusion pressure
      (ICP) in ventilated and sedated patients. Changes in therapeutic intervention
      appear to be initiated in response to changes in a number of differing
      parameters. It is suggested that it may not be appropriate to use the Glasgow
      Coma Scale as a neurological assessment tool in ventilated and sedated patients.

PMID- 11235413
TI  - Will nursing ICU patients in semi-recumbent positions reduce rates of nosocomial
      infection?
AB  - Ventilator-associated pneumonia is the main cause of ICU-acquired infection.
      Infection significantly increases mortality, length of ICU stay and costs (both
      financial and humanitarian). Ventilator-associated pneumonia is usually caused by
      aspiration. Ventilator-associated pneumonia risks are highest among patients who
      are fed through a nasogastric/orogastric tube. A semi-recumbent position reduces
      the risk of aspiration, so should reduce the risk of acquiring ventilator
      associated pneumonia.

PMID- 11235414
TI  - Organisational culture and consultant nurse outcomes: Part 1--Organisational
      culture.
AB  - Organisational culture is presented as a complex concept underpinned by specific
      values, beliefs and assumptions that account for the way things are done. Strong
      organisational cultures and a number of other attributes are highlighted as
      having influence on performance. The role of leadership is recognised as key to
      facilitating cultural change, as is the use of approaches which clarify values
      and highlight contradictions between espoused culture and culture in practice. A
      three-year study in which a consultant nurse post in critical care was
      operationalised demonstrated the achievement of an organisational culture with
      positive impact on the unit in which it was based, on practitioners and their
      practice, and also on the trust. Transformational leadership combined with other
      facilitative processes, expertise in the practice of nursing, and other subroles
      of the consultant nurse are further highlighted as influential.

PMID- 11235415
TI  - Moving towards reality: an open review.

PMID- 11235416
TI  - Maintaining confidentiality and information-giving in intensive care.
AB  - Confidentiality in the intensive care unit (ICU) is difficult to maintain. The
      needs of relatives to have information must be balanced against the patient's
      right to confidentiality. Disclosure of confidential information has to be
      warranted at an individual level. Guidelines to assist in this dilemma do not
      appear to have been developed. A need to address these issues as a matter of
      relative urgency is quantified.

PMID- 11235417
TI  - Using competencies to promote a learning environment in intensive care.
AB  - Nurses need to be able to demonstrate not only a sound knowledge base but the
      ability to link theory to practice. Nursing is a practical profession requiring
      skills of safe management, particularly in the care of critically ill patients.
      Such management includes the ability to make effective assessments and initiate
      appropriate therapy, as well as a duty to understand and utilise supportive
      technology in a competent manner. This paper describes how the role of the
      lecturer practitioner supports an appropriate learning environment in the
      intensive care unit (ICU).

PMID- 11235419
TI  - Effective clinical supervision.

PMID- 11235418
TI  - Anticoagulation in continuous veno-venous haemofiltration.
AB  - The reasons for introduction of a heparin protocol are explained, with best
      practice principles of a protocol stated. The pharmacological properties of
      heparin are explained, and standardisation of monitoring procedures discussed.
      The responsibilities of the nurse in both laboratory and clinical monitoring of
      the effects of heparin are discussed. The use of an algorithm to alter heparin
      dosages against APPT results is justified.

PMID- 11235420
TI  - Nurse practitioners: the future.

PMID- 11235421
TI  - Mixing cultures the challenges for nursing.

PMID- 11235422
TI  - Developing team effectiveness.

PMID- 11235423
TI  - Financial times and the economist thought it significant enough to lead on it.

PMID- 11235424
TI  - Educating the doctors.

PMID- 11235425
TI  - Lightening the load.

PMID- 11235426
TI  - Widening the membership--widening the professional workforce?

PMID- 11235427
TI  - Enabling act.

PMID- 11235428
TI  - Hemodynamic and sympathetic nervous system responses to stress during the
      menstrual cycle.
AB  - In this study, the impact of menstrual cycle phase on hemodynamic and sympathetic
      nervous system responses was examined during exposure to a battery of laboratory
      stressors. Participants were 40 healthy premenopausal women, aged 26 to 51.
      Impedance cardiography was used to measure stroke volume, heart rate, and cardiac
      output. Systemic vascular resistance was derived on the basis of concurrently
      recorded blood pressure and cardiac output. The menstrual cycle's effect on the
      sympathetic nervous system response was explored by evaluating plasma
      catecholamine responses during stress. In luteal compared with follicular
      subjects, systemic vascular resistance was significantly lower during all stress
      tasks (P < 0.03). Catecholamine responses were also significantly lower in luteal
      subjects (P < 0.004). The results suggest that the sympathetic nervous system may
      respond to stress differently during different phases of the menstrual cycle.
      This finding has implications for understanding "whitecoat hypertension" in
      women, and highlights the need to measure blood pressure during several office
      visits. Perhaps high blood pressure readings recorded during the follicular phase
      should be reexamined during the luteal phase before considering pharmacologic
      intervention.

PMID- 11235429
TI  - Pain: neuroanatomy, chemical mediators, and clinical implications.
AB  - Most pain information begins at simple, naked nerve endings called nociceptors
      that form a functional pain unit with nearby tissue capillaries and mast cells.
      Tissue injury causes these nerve terminals to depolarize, an event that is
      propagated along the entire afferent fiber eventuating in sensory impulses
      reaching the spinal cord. This firing of primary afferent fibers at the site of
      tissue injury causes axonal release of vesicles containing neuropeptides such as
      substance P, which acts in an autocrine and paracrine manner to sensitize the
      nociceptor and increase its rate of firing. Cellular damage and inflammation
      increase concentrations of other chemical mediators such as histamine,
      bradykinin, and prostaglandins in the area surrounding functional pain units.
      These additional mediators act synergistically to augment the transmission of
      nociceptive impulses along sensory afferent fibers. Primary fibers travel from
      the periphery to the dorsal horn where they synapse on secondary neurons and
      interneurons. When activated, interneurons exert inhibitory influences on further
      pain signal trafficking. Efferent supraspinal influences, in turn, determine the
      activity of interneurons by releasing a variety of neurotransmitter substances,
      thus resulting in a high degree of modulation of nociception within the dorsal
      horn. Events occurring in the periphery and in the dorsal horn can cause a
      dissociation of pain perception from the presence or degree of actual tissue
      injury. These phenomena involve many chemical mediators and receptor systems, and
      can increase pain experience qualitatively, quantitatively, temporally, and
      spatially. The complexity and plasticity of the nociceptive system can make
      clinical management of pain difficult. Undestanding the structure and chemical
      signals associated with this system can improve the use of existing analgesics
      and provide targets for development of newer and more specific pain-fighting
      drugs.

PMID- 11235430
TI  - Pathophysiology and implications for treatment of acute respiratory distress
      syndrome.
AB  - Acute respiratory distress syndrome is a complex group of signs and symptoms
      caused by direct or indirect lung injury. In spite of decades of research, it is
      still associated with a high mortality rate. Pathogenesis of this disease is
      related to alveolar endothelial and epithelial cell injury and associated release
      and sequestration of inflammatory mediators and cells, including cytokines and
      neutrophils, respectively. Pharmacologic interventions have been largely
      unsuccessful, and ventilation strategies to support oxygenation while limiting
      ventilator associated lung injury have not demonstrated any significant
      reductions in the mortality rate. However, novel therapies are in development,
      based on the knowledge of the pathologic processes of acute respiratory distress
      syndrome. In this article an overview of the disease process and mediator
      involvement is presented, followed by a review of pharmacologic and ventilation
      treatments currently in use or under study.

PMID- 11235431
TI  - Risk factors for nosocomial pneumonia in critically ill trauma patients.
AB  - Nosocomial pneumonia is the most common pulmonary complication in trauma patients
      and the leading cause of death in nosocomial infections. A comprehensive review
      of pneumonia studies is provided. The Centers for Disease Control's nosocomial
      pneumonia pathogenesis model is reviewed and was used to guide the selection of
      risk factors evaluated in this study. The purposes of this research were to
      identify underlying dimensions (factors) of variables that increase the risk of
      nosocomial pneumonia and to identify predictors of nosocomial pneumonia in
      critically ill trauma patients.

PMID- 11235432
TI  - Biologic markers of airway inflammation in asthma.
AB  - Asthma is a serious chronic disease of the airways that affects approximately 14%
      of the population in the United States. The fundamental pathophysiologic
      component of asthma is airway narrowing, which causes airflow obstruction. Both
      inflammation and bronchoconstriction contribute to airway narrowing. The
      pathogenesis of airway inflammation in asthma and the natural history of the
      disease are the subject of intense research and study in many countries of the
      world. The mechanisms of airway inflammation are only partially understood but
      are the basis for the devastating symptoms that affect the quality of life of
      millions of people. Treatment of asthma is directed at decreasing airway
      inflammation to gain long-term control of the disease.

PMID- 11235433
TI  - Role of nucleotides and nucleosides in the regulation of cardiac blood flow.
AB  - The regulation of blood flow in the heart on a moment-to-moment basis is
      essential to meet changes in the oxygen demands of cardiac muscle. The signals
      that subserve this regulation are not all firmly established. Although the
      formation and release of adenosine by cardiac muscle during periods of hypoxia or
      regional ischemia in the heart are well known to produce regional vasodilation
      and salvage of at-risk myocardium, these extracellular actions of adenosine are
      believed to occur abluminally and thus do not explain the origin or predict the
      potent actions of intravascular adenosine. The notion that purines such as
      adenosine and adenosine 5'-triphosphate (ATP) might be available to act in the
      lumen of the blood vessel has been proposed by the authors and others to help
      explain the regulation of blood flow in the heart in nonpathologic states. This
      article details the background and current understanding of the vascular actions
      of adenosine and ATP, defines the Nucleotide Axis Hypothesis, and reviews
      clinical studies in which its likely importance in the maintenance of blood flow
      in the heart has been investigated.

PMID- 11235434
TI  - Reperfusion injury of cardiac myocytes: mechanisms, treatment, and implications
      for advanced practice nursing.
AB  - Reperfusion injury is a major complication associated with the restoration of
      blood flow to previously ischemic myocardium. The deleterious effects associated
      with reperfusion injury result from several complex pathologic mechanisms. The
      complexity of these mechanisms makes development of treatment protocols
      difficult. The purpose of this article is to review the pathophysiology of
      reperfusion injury and currently indicated therapies. Implications for advanced
      practice nursing and areas for further research are presented.

PMID- 11235435
TI  - Channelopathies: potassium-related periodic paralyses and similar disorders.
AB  - Channelopathy is a term used to describe clinical problems caused by disorders of
      membrane ion channels. Included in this disease category are certain types of
      periodic paralyses, ataxia, myotonia, migraine headache, epilepsy,
      nephrolithiasis, and long QT syndrome. This article briefly summarizes membrane
      ion channel structure and function and details several relatively common
      channelopathies. In hyperkalemic periodic paralysis, mutant skeletal muscle
      sodium channels fail to close completely after an action potential. This evokes
      two apparently opposite symptoms: myotonia (caused by a small depolarization and
      repetitive excitation) or paralysis (caused by larger depolarization and
      inexcitability). In hypokalemic periodic paralysis, mutation affects the closing
      of skeletal muscle calcium channels, causing transient paresis or paralysis. The
      task of the advanced practice nurse is to recognize these disorders, institute
      appropriate prophylactic measures and treatments, monitor symptom progression,
      and avoid complications. Understanding of channelopathies is advancing rapidly.
      On the horizon are therapies tailored to counter specific membrane ion channel
      defects.

PMID- 11235436
TI  - Regulation of uterine contraction: mechanisms in preterm labor.
AB  - Preterm labor (PTL) is defined as uterine irritability accompanied by cervical
      dilation and/or effecement that occurs before 37 weeks gestation. In most cases,
      PTL becomes preterm delivery (PTD), accounting for 8% to 10% of births in the
      United States. Fetuses born before 37 weeks' gestation are at risk for a
      multitude of health and developmental problems. Most perinatal morbidity and
      mortality in the United States are caused by PTL. It is a costly problem, in both
      monetary and human terms. Although some risk factors have been identified, they
      by no means identify, in advance, every case of PTL and PTD. Despite the
      understandable emphasis on attempts to find and test risk factors that predict
      PTL, the ultimate benefit--preventing PTD--will come only from an understanding
      of the physiologic mechanisms of parturition and how to halt those processes when
      they occur too early. This article reviews current approaches to preventing PTD,
      describes the biology of myometrial contraction, and discusses recent progress
      from several laboratories including the authors' that may shed light on
      approaches to inhibit uterine contractility in the setting of PTL.

PMID- 11235437
TI  - Tracheobronchial trauma associated with airway management in neonates.
AB  - Airway management procedures are an integral part of caring for the newborn
      infant with respiratory compromise. Concomitant with these interventions are
      latrogenic consequences that result in varying degrees of trauma to the
      tracheobronchial tree. Common interventions such as intubation, mechanical
      ventilation, use of heated and humidified gases, and endotracheal suctioning are
      discussed using research-based literature that evaluates the injury to the
      trachea and the mucociliary transport system.

PMID- 11235438
TI  - Sudden infant death syndrome: a toxic response.
AB  - Causes of sudden infant death syndrome (SIDS) remain elusive. Much of the current
      literature points to an infectious cause with a role for proinflammatory
      cytokines and septic shock in stimulating an overwhelming response in an infant.
      This article reviews the literature and possible causes of this devastating
      condition.

PMID- 11235439
TI  - Federal support for the preparation of the clinical nurse specialist workforce
      through Title VIII.

PMID- 11235440
TI  - The effect of preprocedure teaching, relaxation instruction, and music on anxiety
      as measured by blood pressures in an outpatient gastrointestinal endoscopy
      laboratory.
AB  - A gastrointestinal examination can be frightening to patients. Abnormally
      elevated blood pressure and pulse caused by anxiety often are present on
      admission to the hospital. These elevated vital signs are then used as the
      baseline vital signs for the patient's hospital stay. The first purpose of this
      study was to determine whether vital signs are elevated because of anxiety on
      admission to the hospital and how much they decrease after sedation. The second
      purpose of this study was to explore the effect of instruction about relaxation
      and the use of music relaxation audio tapes in decreasing patient anxiety.
      Patients undergoing endoscopic examinations for the first time were randomly
      assigned into two groups. Patients in the treatment group were given brief
      instructions in relaxation and provided with an audio tape player and relaxation
      music. Statistical analysis using multivariate analysis of variance (MANOVA)
      comparing differences between control and treatment groups over time showed that
      there was a significant main effect for diastolic blood pressure. Subjects in the
      treatment group had significantly lower blood pressures throughout the entire GI
      procedure. There was no significant difference between groups regarding the
      amount of medication used. Music combined with relaxation is an inexpensive
      nursing intervention for patients in relaxing during a GI examination.

PMID- 11235441
TI  - Nurse endoscopist training: the next step.
AB  - Nurses have been successfully performing flexible sigmoidoscopy since the early
      1970s. There are numerous studies, in both medical and nursing literature,
      indicating that nurses can perform this traditional physician role safely and
      efficiently. Both the American Society of Gastroenterology Endoscopists (ASGE)
      and Society of Gastroenterology Nurses and Associates (SGNA) have endorsed this
      practice. Programs appropriate for training the nurse endoscopist, however, have
      not been defined. Although similarities exist in the literature about how nurses
      and other nonphysician endoscopists are trained, there are also many
      discrepancies. If nurses are to take a proactive stance in overseeing nursing
      practice, objective criteria and clinical competencies need to be established.
      This is the next step in establishing standard acceptance by the medical
      community and public.

PMID- 11235442
TI  - Parish nursing: renewing a long tradition of caring.
AB  - Parish nurses are experienced registered nurses committed to helping people meet
      the health needs of their body, mind, and spirit. To fulfill this goal, parish
      nurses must be health educators and counselors, referral sources, facilitators,
      patient advocates, healthcare plan interpreters, and multitalented coordinators.
      The parish nurse uses the skill of nursing assessment of individual and
      congregational needs and matches the assessment findings to available resources.
      The parish nurse also advocates increased awareness of health-related issues that
      lead to earlier and more effective treatment and care. All ages benefit within a
      context of personal caring and attention offered by a parish nursing model that
      is often lacking from healthcare delivery systems. Congregations of all sizes,
      both urban and rural, have successfully started parish nurse programs. Parish
      nursing programs are a religious response to help bring wholeness and healing to
      the faith community. The purpose of this article is to explore parish nursing as
      it has evolved into a model of health care delivery contributing to the
      empowerment and health of both the individual and the community.

PMID- 11235443
TI  - Nurse-assisted PEG in pediatric patients.
AB  - Percutaneous endoscopic gastrostomy (PEG) has become an accepted technique to
      provide enteral access in children. At the author's institution, this procedure
      has evolved from being performed by a surgeon and a pediatric gastroenterologist
      to being performed by two gastroenterologists. As studies in the adult population
      have shown the efficacy of training an experienced endoscopy nurse to assist with
      PEG placement, it was decided to develop a nurse-assisted PEG program for
      pediatric use and to evaluate the safety of this method. Data were collected on
      147 consecutive patients undergoing PEG from June 1997 to May 1999. Sixty-nine
      patients had nurse-assisted PEGs, and 78 had a gastroenterology fellow-assisted
      PEG. Both groups had a pediatric gastroenterology attending physician as the
      endoscopist. The two groups were compared for periprocedure complications. No
      significant difference in the complication rate was found between the two groups.
      Our experience suggests that PEGs can be safely placed in the pediatric
      population using a trained endoscopy nurse as first assistant.

PMID- 11235444
TI  - SGNA guidelines for nursing care of the patient receiving sedation and analgesia
      in the gastrointestinal endoscopy setting.

PMID- 11235445
TI  - A product review for sterile India ink from PERMARK.

PMID- 11235446
TI  - Surviving the tornadoes of life.

PMID- 11235447
TI  - Endoscopic ultrasonography (EUS) and EUS-guided fine needle aspiration for
      accurate staging of rectal cancer: explanation of tumor staging and a case
      report.
AB  - This article describes the diagnosis, staging, and therapeutic options for rectal
      cancer and the importance of endoscopic ultrasonography (EUS) and EUS-guided fine
      needle aspiration (FNA) as a relatively new diagnostic modality. A case study is
      presented from initial diagnosis through surgery to illustrate how EUS and EUS
      guided FNA influenced the treatment plan. Discussion focuses on rectal cancer and
      the importance of early detection through routine screening. The internationally
      accepted Tumor Node Metastasis (TNM) staging classification system for rectal
      cancer is included, followed by a description of EUS and EUS-guided FNA with
      regard to accuracy in staging. In conclusion, the various stage-dependent
      treatment options available for rectal cancer that can be individualized based on
      the patient's medical problems and preferences are discussed.

PMID- 11235448
TI  - Prepare to publish.
AB  - "I couldn't possibly write an article." "I don't have anything worthwhile to
      write about." "I am not qualified to write for publication." Do any of these
      statements sound familiar? This article is intended to dispel these beliefs. You
      can write an article. You care for the most complex patients in the health care
      system so you do have something worthwhile to write about. Beside correct
      spelling and grammar there are no special skills, certificates or diplomas
      required for publishing. You are qualified to write for publication. The purpose
      of this article is to take the mystique out of the publication process. Each step
      of publishing an article will be explained, from idea formation to framing your
      first article. Practical examples and recommendations will be presented. The
      essential components of the APA format necessary for Dynamics: The Official
      Journal of the Canadian Association of Critical Care Nurses will be outlined and
      resources to assist you will be provided.

PMID- 11235449
TI  - Research involving humans: dilemmas in ethics approval.

PMID- 11235450
TI  - Nursing research or quality improvement (QI): what standard should we expect?

PMID- 11235451
TI  - Managing central venous catheters: a prospective randomised trial of two methods.
AB  - A randomised, prospective study was conducted to evaluate the impact on central
      venous catheter (CVC) infection when fluids and lines connected to a CVC were
      changed using a 'sterile' compared to an 'aseptic, non-touch' technique. The
      study sought to determine whether there were any differences in CVC tip
      colonisation (CTC) or CVC-related bacteraemia (CRB) as a result of the technique
      used for fluid and line changes. In the sterile technique (control) group, fluids
      and tubing were changed using full sterile technique. In the aseptic, non-touch
      (experimental) group, fluids and tubing attached to the CVC were changed using
      only a small sterile drape and a 2-minute clinical hand wash. When the CVC was
      removed, the tip was sampled and cultured using the semi-quantitative method.
      Blood cultures were also collected. In all, 111 samples from 79 patients were
      included in the trial: 61 in the sterile technique group and 50 in the non-touch,
      aseptic technique group. Results showed a CTC rate of 31 per cent in the control
      group and 14 per cent in the experimental group, while the CRB rate was 8.2 per
      cent and 6 per cent respectively. The most common organisms cultured were
      Staphylococcus aureus and S. epidermis respectively. This study indicates that it
      is safe to change fluids and lines attached to CVCs using the aseptic, non-touch
      technique, which has resulted in significant financial savings through less use
      of equipment and less nursing time required to perform fluid and line changes.

PMID- 11235452
TI  - Refractory hypotension in trauma: a case study.
AB  - In the patient with blunt trauma, diagnosis of the cause of ongoing hypotension
      may be difficult. A number of causes may contribute to refractory hypotension,
      either alone or in combination. However, by following standard algorithms for the
      management of these patients, causes can be excluded or identified, then managed
      appropriately. The following case study highlights one of the diagnoses of
      exclusion for refractory hypotension in the blunt trauma victim. Ongoing
      considerations and implications for the nursing care of spinal injured patients
      are also discussed.

PMID- 11235453
TI  - Temperature taking in the ICU: which route is best?
AB  - Temperature measurement in an intensive care environment requires accurate
      estimation of core temperature via reliable equipment. Intermittent rectal probes
      were routinely used to measure core temperature in all extubated patients
      admitted to the Intensive Care Unit (ICU) which was the setting for this project.
      The nursing and medical staff identified various problems associated with this
      practice and a quality improvement project was implemented to compare
      temperatures recorded using three different routes: rectal, infrared tympanic and
      nasopharyngeal. Forty-nine patients were included in the study. Nasopharyngeal
      temperature measurements were recorded for all intubated patients and rectal
      temperature measurements were recorded for all extubated patients. During data
      collection, infrared tympanic temperature measurements were recorded at the same
      time as all other temperature measurements. The main comparison was between the
      rectal route and the infrared tympanic route because of the problems with the
      rectal probes that had been identified by staff. The results indicated
      statistically significant correlations between temperatures measured at the
      different sites. These results confirmed previous literature and the ICU involved
      in this study replaced rectal temperature measurement via intermittent probe
      insertion with infrared tympanic thermometry for the measurement of core
      temperature in extubated patients.

PMID- 11235454
TI  - Conducting a systematic review.
AB  - In response to the growing volume of health care literature and the variable
      quality of reported studies, systematic reviews have increasingly been used to
      guide health care decisions because of their rigorous summary of the research.
      Systematic reviews utilise planned methods of identifying, appraising, then
      summarising the results from individual studies. The steps in performing a
      systematic review include: preparing a detailed research protocol; selecting
      criteria for inclusion of articles in the review; systematically searching the
      published and unpublished literature; determining which articles meet the
      predefined inclusion criteria; critically appraising the quality of the research;
      extracting outcome data from the research report and statistically combining
      data, where appropriate, in order to summarise the best available evidence on the
      topic of interest. These processes are documented in the systematic review
      report, and can be subject to peer review and critique like other research.

PMID- 11235455
TI  - A nursing-implemented sedation protocol and the duration of mechanical
      ventilation.

PMID- 11235456
TI  - Managerial implications of calculating optimal nurse staffing in medical units.
AB  - A critical managerial decision in health care organizations is the staffing
      decision. We offer a model to derive an optimum mix of different staff categories
      that minimizes total cost subject to constraints imposed by the patient acuity
      system and minimum staffing policies in a medical unit of Fairbanks Memorial
      Hospital, Alaska. We also indicate several managerial implications on how our
      results and their sensitivity analyses can be used effectively in decision making
      in a variety of categories.

PMID- 11235457
TI  - Bein' lazy.

PMID- 11235458
TI  - Ethical issues in perianesthesia nursing.
AB  - Ethical issues have historically been a significant focus in perianesthesia
      nursing. Issues of safety, privacy, and informed consent are never far from the
      consciousness of the perianesthesia nurse. As the national organization that
      serves as a clearing ground for issues and goals of perianesthesia nursing
      practice, ASPAN has begun the process of developing a code of ethics for
      perianesthesia nursing practice. This report is designed to provide a brief
      review of the important definitions and principles that are used in the
      discussion of ethics, review the contemporary forces that mandate and justify the
      development of an ethical code, and explore how such a code may function to aid
      and guide nursing practice.

PMID- 11235459
TI  - A study in time: performance improvement to reduce excess holding time in PACU.
AB  - The early 1990s saw prolonged patient stays in the PACU at St Joseph's Hospital
      of Atlanta, a 350-bed tertiary-care hospital. PACU discharge was delayed for
      various reasons: no room available, no receiving nurse, no help to transport
      patients, and prolonged recovery from anesthesia. These prolonged stays resulted
      in occasional backups in receiving patients from the OR, as well as having alert
      patients among arriving patients, unstable patients, and patients with nausea or
      pain. These delays were perceived to be stressful to the patient, their families,
      and to the staff. It was also expensive for the patient and costly in terms of
      nursing care. A multiyear, intermittent study was conducted to seek and implement
      solutions to this problem and evaluate the results. This article details these
      efforts and the resulting accomplishments.

PMID- 11235460
TI  - The effect of arthroscopic irrigation fluid warming on body temperature.
AB  - The use of room temperature solutions for body cavity irrigation during surgical
      procedures can lead to the development of perioperative hypothermia. Hypothermia
      during this period causes patient discomfort, increases oxygen consumption,
      interferes with the clotting cascade, and increases the length of hospital stay.
      Perioperative hypothermia in anesthetized patients also contributes to extended
      sedation, delayed emergence, and prolonged recovery from neuromuscular blockade.
      Twenty-four adult American Society of Anesthesiologists (ASA) class I and II
      patients were randomly assigned to receive warmed arthroscopic irrigation
      solution or room-temperature irrigation solution in this randomized, prospective
      study. Tympanic temperatures were monitored every 15 minutes throughout the
      surgical and postanesthesia recovery periods. P < .05 was considered significant.
      Statistical comparison of the mean percent temperature decrease from preoperative
      baseline between the 2 groups did not support the hypothesis that patients
      receiving warmed irrigation solution would maintain a higher core body
      temperature than those receiving room temperature solution.

PMID- 11235461
TI  - Not a social event: the follow-up phone call.
AB  - The follow-up phone call provides an invaluable opportunity to evaluate patient
      education, identify trends that may require improvement in practice, determine
      compliance with discharge instructions, and assess overall impressions of
      performance. This process supports efforts to "close the loop" on patient
      contact.

PMID- 11235462
TI  - Endovascular abdominal aortic aneurysm repair.
AB  - Endovascular abdominal aortic aneurysm (AAA) repair is a new, less-invasive
      approach to traditional AAA repair. This innovative technique may provide the
      patient with significant benefits, including a less-invasive procedure, fewer
      postoperative complications, and early discharge home. In many cases, the patient
      will be transferred after the procedure to the PACU and then discharged to the
      general floor or telemetry unit, eliminating the need for an ICU stay.

PMID- 11235463
TI  - Rapacuronium bromide.
AB  - Rapacuronium bromide (Raplon; Organon Inc, West Orange, NJ) is a new, fast-onset,
      short-duration surgical muscle relaxant. While anesthesia providers are learning
      how to use this new relaxant, PACU nurses must become aware of the potential
      problems associated with rapacuronium. This article compares and contrasts the
      effects of succinylcholine and rapacuronium.

PMID- 11235464
TI  - Managing conflict/employee counseling.
AB  - Managers and nurse leaders can enhance skills and techniques to manage conflict
      and subsequent counseling of employees in the workplace. Stress, conflict, issues
      of miscommunication, and a poor job performance can be handled in a focused,
      orderly manner. Corrective action plans and documentation of counseling sessions
      are suggested. A framework for managers to perform self-assessment in counseling
      performance is provided. Developing specific competency checklists for managers
      and completing them on an annual basis validates important aspects of the role of
      nurse managers.

PMID- 11235465
TI  - 10-step Joint Commission Accreditation of Healthcare Organizations' compliance
      plan.
AB  - Meeting the Joint Commission Accreditation of Healthcare Organizations' (JCAHO)
      requirements can sometimes seem overwhelming. This article describes the process
      that Southern Hills Medical Center in Nashville, Tennessee has used to prepare
      staff to meet this goal. The key to the successful use of this process is active
      staff member involvement and making learning fun. This plan was developed by
      Southern Hills Medical Center and is not affiliated with or endorsed by the
      JCAHO.

PMID- 11235466
TI  - Perianesthesia applied research.
AB  - Research is important for perianesthesia nursing to validate and to advance
      patient care. Evidence-based nursing practice is discussed as one method of
      advancing PACU nursing practice. PACU nurses are encouraged to submit pain study
      reviews as a beginning to evidence-based nursing practice. Resources are given
      for research method techniques.

PMID- 11235467
TI  - New year's resolutions.

PMID- 11235468
TI  - [Nursing news in senology: creation of an ambulatory nursing clinic].
AB  - The IEO has starded an outpatient senology clinic conducted by nurses, and
      inspired by the successful experience of a similar clinic at the Gustave Roussy
      Institute of Paris. The purpose of the clinic is to expedite a series of
      procedures best carried out prior to hospital admission. First, the patient
      presents for the selection and examination of pre admission tests, following
      which the standard examinations related to the admission are programmed; the
      results are then examined, and the clinical record prepared for consignment to
      the Division the day before admission. The service began in April 1998 and has
      already received 750 patients.

PMID- 11235469
TI  - [Nursing and quality of life in peritoneal dialysis patients].
AB  - The aim of the present study was to bring to the attention some problems of
      people in peritoneal dialysis and improve the quality of care through some
      Nursing intervention.

PMID- 11235471
TI  - [Analysis of quality as instrument of accreditation].

PMID- 11235470
TI  - [Quality, efficiency and ethics in the nursing service--disrupted by collision or
      possible convergence?].

PMID- 11235473
TI  - [Simple methods to prevent accidental falls].

PMID- 11235472
TI  - [The nursing profession celebrates its past history and is looking foreward to
      its future].

PMID- 11235474
TI  - [Care for the demented: the use of elements from their life experience].

PMID- 11235475
TI  - [Enteral feeding: early diagnosis of undernurishment].

PMID- 11235476
TI  - [Community housing in old age: to live and be treated as in the family
      environment].

PMID- 11235477
TI  - [Prevention of back pain: the use of lifting-chairs].

PMID- 11235478
TI  - [Emergency service is part of nurses' working time].

PMID- 11235479
TI  - [Quality of life: without past and future there is no significant present].

PMID- 11235480
TI  - [Food and fluid deprivation in the diet of the aged: how do nurses find the
      proper balance?].

PMID- 11235481
TI  - [There are many plants to treat rheumatic diseases].

PMID- 11235482
TI  - [To reduce excessive costs of incontinence: HILMAS may help (Hartmann
      Incontinence Logistic Management and Assessment System)].

PMID- 11235483
TI  - [To live independently into old age].

PMID- 11235484
TI  - [A new challenge in terminal care].

PMID- 11235485
TI  - [To estimate capabilities and problems of the aged].

PMID- 11235486
TI  - [Accidental falls in the old age home: frequency, causes, consequences and risk
      factors].

PMID- 11235487
TI  - [Attention deficit and infantile hyperactivity].
AB  - Hyperactivity is a very common disorder in children (specially males) that today
      is considered as a clinical syndrome by scientific medicine. American Psychiatric
      Association establishes 10 symptoms to diagnose it, but they can be resumed in
      three characteristics: Impulsivity, Distraction, and Hyperactivity. There are
      different ways to treat it, but psychiatric medication has major risks in
      children. From complementary medicine we can find several aids in changing diet
      patterns and supplementing with vitamins or minerals. Chocolate, sugar,
      sweeteners, additives, preservatives, dyes, can enhance the incidence of this
      syndrome; instead the supplementation with lipids rich in PUFA's can prevent it.
      B complex vitamins, magnesium, copper, manganese or calcium can be interesting
      and in herbal medicine, sedative plants like passion flower, valerian or lemon
      balm are useful aids. Also liquorice, fennel and berries can be used for
      different physiological actions.

PMID- 11235488
TI  - [Cutaneous cysts, minor surgery].
AB  - For the nursing profession, the practice of minor surgery means the recovery of
      an activity which possesses a long historical tradition in our profession and an
      experience for nurses to provide a specific service in health care. The
      incorporation of minor surgery as one of the services offered by Primary
      Outpatient Clinic Care is taking place slowly but surely, especially in light of
      the advantages it provides. For several years now, some health professionals,
      nurses and doctors belonging to the Andalucian Health Services, have been
      actively working on the development and implementation of Minor Surgery Programs
      inside the Health Clinics of our community. One of our lines of work has been the
      development of protocols for the treatment of the most habitual lesions by means
      of minor surgery. Among these are cutaneous cysts whose protocol we present in
      this article.

PMID- 11235489
TI  - [In-hospital accidental falls: a reality].
AB  - OBJECTIVE: To describe the patients who suffer falls in our center and test the
      sensibility of risk factors currently defined in order to correctly identify them
      and apply corrective measures. MATERIALS AND METHODS: We studied the falls which
      occurred between March 1996and May 1998. The authors analyze the circumstances of
      the fall as well as the characteristics of those patients who suffered these
      falls. In the case of patients who suffered more than one fall, we analyzed just
      the first one. RESULTS: The 12,894 patients registered in this hospital during
      that time period  suffered 192 falls, involving 171 patients. The risk increases
      with age. The majority occurred in patients who are registered for rehabilitation
      after having a vascular cerebral acccident. CONCLUSIONS: the defined risk factors
      are sufficient enough to identify patients at risk, but we should include
      rehabilitation patients as such. The quantity of countermeasures installed to
      prevent falls and their high degree of announcement contrasts with the poor
      identification of those patients considered at risk; we should modify this system
      of identification. It is necessary to include relatives in the prevention of
      falls. This information shall be divulged to the all other hospital sections.

PMID- 11235490
TI  - [Nursing service in Portugal].

PMID- 11235491
TI  - [Contraceptive methods in advanced age].

PMID- 11235495
TI  - Medicare changes: a first glance of problems at home.

PMID- 11235496
TI  - The individualistic nature of healthcare: challenges for public policy.
AB  - Modern healthcare in America is thought to be strongly individualistic in nature
      in that it largely focuses on curative treatment of individuals instead of
      preventive medicine that would affect whole segments of the population. This
      article describes the terms individualism, entitlement, and respect for personal
      autonomy within the context of ethically sound public policy formation.

PMID- 11235497
TI  - The quality of skin care products and their ingredients.
AB  - Several ingredients used in skin products have been criticized as being
      excessively harsh, allergenic, or otherwise unsuitable for use, especially in the
      elderly population. Preservatives, in particular, have been condemned, leading to
      a proliferation of "preservative-free" products. Other descriptive/promotional
      phrases with negative connotations are "fragrance-free" and "emulsifier-free."
      Inferences regarding these designations might suggest that preservatives,
      fragrances, emulsifiers, and a number of other ingredients serve no important
      function, are superfluous in terms of product quality, and, therefore, should be
      left out of all skin products. While this is obviously not the case, neither is
      the obverse. Ingredients used in skin care products should be carefully chosen to
      support or maintain the overall effectiveness and utility of the product, and the
      concentration of such ingredients should be given careful consideration. After
      briefly reviewing skin structure and changes that occur during aging, this
      article examines the concept of product quality. Major nondrug ingredient
      categories will be addressed, including the reasons for using such ingredients in
      skin care products, the products in which they are required, the limitations and
      choices available within each category, and guidelines for product selection.

PMID- 11235498
TI  - Best practices for the prevention and treatment of venous leg ulcers.
AB  - Chronic venous insufficiency is the most common cause of leg ulcers. Its
      incidence increases as the population ages. Managing venous leg ulcers involves
      treating the cause, optimizing local wound care, and addressing patient-centered
      concerns. The cornerstone of the diagnosis of chronic venous insufficiency
      includes demonstrating venous disease. The clinician must rule out significant
      coexisting arterial disease by performing a thorough clinical assessment and
      obtaining an ankle brachial pressure index. The most important aspect of
      treatment is resolving edema through high compression therapy for those
      individuals with an ankle brachial pressure index greater than or equal to 0.8.
      Other components of successful chronic venous insufficiency management include
      increasing mobility and medical management. Selected patients may respond to
      surgery, biologicals, adjunctive therapies, and lifestyle enhancements. Twelve
      recommendations are made incorporating current best clinical practices and expert
      opinion with available research. The approach to venous disease is best
      accomplished through a multidisciplinary team that revolves around the active
      participation of patients and their families. The authors' intent is to provide a
      practical, easy-to-follow guide to allow healthcare professionals to provide best
      clinical practices.

PMID- 11235499
TI  - Petrolatum versus Resurfix ointment in the treatment of pressure ulcers.
AB  - This study compares the therapeutic effects of a new topically applied,
      nonprescription medication that has been introduced for re-epithelialization of
      ulcers and erosions of the skin, with petrolatum in treating pressure ulcers of
      shallow depth (Stage I and Stage II). A 6-week, randomized, double-blind study
      was performed on 19 patients with Stage I or Stage II pressure ulcers. The
      patients received either the new nonprescription medication or petrolatum, which
      served as a control. After the course of the study, the study ointment effected
      resolution in a majority of pressure ulcers (9 out of 10), while only one out of
      three ulcers treated with petrolatum resolved in the same time period. These
      preliminary results show that the study ointment is a safe and effective
      treatment for Stage I and II pressure ulcers.

PMID- 11235500
TI  - Where the rubber meets the road.

PMID- 11235501
TI  - [Corrado Tommasi-Crudeli, hygienist].
AB  - To celebrate the centennary of the death of Prof. Corrado Tommasi-Crudeli, the
      founder and first director of the "Istituto di Igiene Sperimentale" in Rome
      (1885), the authors remember this eminent scientist who spent his life not only
      working in scientific experimental research but also was a member of the
      Parliament and promotor of important laws regarding social and health problems.
      It should be remembered that, prior to 1870, Hygiene was not a discipline in
      itself, but was part of Medicine and taught in theoretical courses such as Public
      Health Inspection and Legal Medicine. On the basis of the discoveries by
      Pettenkofer in Munich (1883) and Koch in Berlin (1885), the Prof. Tommasi-Crudeli
      created the foundations of Hygiene in Rome as an independent subject, strictly
      linked to experiments thus realizing a theoretic/practical discipline. From that
      time on words, Hygiene has evolved and grown, to become a specialised subject
      whose objectives are epidemiological studies, prevention of diseases and
      promotion of health, and whose important contributions to other branches such as
      Microbiology, Parasitology and Medical Statistics have helped them to become
      independent disciplines.

PMID- 11235502
TI  - Direct viable count as test for toxicity assessment: the effects of four metals
      on a Salmonella enteritidis strain.
AB  - The toxicity of synthetic sewage containing increasing concentrations of arsenic
      (.125, .25, .5, 1.0 mg L-1), cadmium (.02, .05, .1, .2 mg L-1), lead (.2, .5,
      1.0, 2.0 mg L-1) and nickel (.5, 1.0, 2.0, 4.0 mg L-1) has been investigated by
      determining the total direct count (TDC) and the direct viable count (DVC) of
      Salmonella enteritidis by means of an immunofluorescence technique (IFA). This
      has been done in order to evaluate the possibility of using the IFA technique to
      estimate the toxicity of complex effluents. Arsenic, cadmium and nickel produced
      a concentration-dependent reduction in the number of viable bacterial cells. This
      was more clear when the viable bacterial cells were considered than when only the
      culturable part was used. Lead did not show a concentration-dependent and
      reproducible effect. At the highest concentrations allowed by the Italian
      wastewater regulations, lead, cadmium, arsenic and nickel reduced the
      viable/total bacterial cells ratio to 74.5%, 68.5%, 28.4% and 6.9%, respectively.
      The toxic effects of the metals were also tested using the standard Microtox
      assay.

PMID- 11235504
TI  - Microbiological characterization of freatobiont organisms: trial of an analytical
      protocol and hygienic implications.
AB  - The objective of the present study lies in verifing the applicability of an
      analytical protocol to characterize the microbiology of the surface and gut of
      freatobiont organisms. The fundamental hypothesis of the study is that the
      subsurface microinvertebrates represent a protective condition for bacteria,
      whose presence in potable spring water is rigorously excluded by european
      standards of quality. The study was conducted between August 1996 and March 1998.
      Sediment samples were collected from the spring system of "Presciano", whose
      waters come from the regional aquifer of the Gran Sasso Massif in Italy
      (L'Aquila, Abruzzo). Drawings of samples were conducted at two different depths (
      70 cm and -150 cm). The extration of the fauna (including copepodes) from
      sediments were achieved with the aid of a Wild M3 microscope. Isolate freatobiont
      organisms were placed in a sterile Petri plate and subjected to three washings.
      The liquids of the second and third washings were microbiological analyzed
      proceeding, in the course of the third washing, to squash the organisms with the
      aid of a sterile iron handle. Among the microinvertebrates, the copepod
      Harpacticoida Nitocrella pescei is the most represented species from the two
      levels of depth. In all, were isolated and identified 106 bacterial species; of
      these species only 12 (11.3%) did not show any adaptation to the temperature of
      35 degrees C. The analytical protocol permitted to make evident a different
      distribution of microbial species between the two kinds of washing liquids, and
      this leads to considerate appropriate the adopted protocol. Even if the number of
      sediment samples analyzed was a few it was identified a great variety of
      microbial genera and species the greater part of which were mesophilic. This is a
      consequence of an adaptability that could be favoured by the presence of
      freatobiont fauna and that concern even microorganisms usually considered "faecal
      contamination indicators".

PMID- 11235503
TI  - Effect of metal mixtures on Salmonella enteritidis viability in synthetic sewage.
AB  - We sought to determine the effect of 26 multiple metals solutions, containing Cd,
      Pb, As and/or Ni, on the viability of Salmonella enteritidis. We used the direct
      viable count effected by immunofluorescence technique (IFA-DVC) in comparison
      with the culturable cell count. The metals concentrations were prepared
      considering the single as well as the overall limits provided by Italian
      regulation on the water pollution. The mixtures containing nickel showed always
      toxicity more elevated than other metal solutions tested. Thus we consider too
      high the nickel law limit. The interactions among the elements, causing generally
      toxicity decrease, are very well assessable by IFA-DVC test. This method permits
      to calculate the lethal concentrations of toxicants on bacteria that play a
      pivotal role on the ecosystem components.

PMID- 11235505
TI  - Virulence factors in Vibrio alginolyticus strains isolated from aquatic
      environments.
AB  - In a microbiological monitoring carried out in various aquatic environment of
      Sardinia Island (Italy) Vibrio alginolyticus with different virulence phenotypes
      appeared widely spread. Hemolysis, hemoagglutination and protease production
      might be together particularly in strains isolated from polluted environments.
      Adherence capacities to two epithelial cells (Hep-2 and Caco-2) available in
      laboratory were widely spread in the examined bacterial strains. The adhesion
      degree was influenced by the utilized cellular clone. The lack of a
      correspondence between adhesion capacity and more traditional virulence tests do
      not permit its replacement at screening level.

PMID- 11235506
TI  - [HACCP (Hazard Analysis and Critical Point system) at a catering service:
      checklist and microbiological examination].
AB  - The A.A. carried out a survey on the functioning of a catering service in Rome.
      The risk analysis assessment was performed by means of a checklist that collected
      systematically all data about the environment, the operators, the food and the
      catering process. The results of the microbiological analysis carried out in the
      CCP's showed that the general conditions of the catering service were not
      satisfactory, but also indicated the validity of the checklist used. This method
      showed a high predictive value and can be useful to improve the application of
      the HACCP system.

PMID- 11235507
TI  - Child malnutrition in north Albania: results from an anthropometric survey.
AB  - In order to assess child malnutrition, an anthropometric cross-sectional survey
      of children aged 0-36 months was conducted in selected rural, urban and
      mountainous areas of Northern Albania in May 1997. The results showed a high
      prevalence of low anthropometric indices in rural and mountainous areas with a
      trend of similar magnitude in northern rural areas. In Northern Albania child
      malnutrition is a public health priority. As the main risk factor for underweight
      we found a recent history of diarrhoea (OR = 2.45) together with female gender
      (OR = 2.28), rural (OR = 2.09) or mountain (OR = 1.61) residency. Absence of
      sanitation, marker of poor housing conditions, also showed a significant
      association (OR = 1.55) with underweight. Low birthweight (OR = 1.12) was
      confirmed as an important risk factor for underweight condition. In conclusion
      these findings underline the importance of support appropriate mother and child
      health and nutritional programmes in rural areas of Northern Albania.

PMID- 11235508
TI  - [Characteristics of voluntarily discharged patients: some reflections and a
      proposal].
AB  - This study compares the characteristics of 492 patients discharged against
      medical advice from the Istituto Dermopatico dell'Immacolata, a Research Hospital
      (335 beds) in Rome specialized in Dermatology, Vascular Surgery and Plastic
      Surgery between 1995 and 1998, with those of 43,110 control patients discharged
      with physicians' approval according to a case-control model. In the multivariate
      analysis, male gender (OR 1.65; 95% CI 1.37-1.98) and residence in Rome area (OR
      1.22; 95% CI 1.02-1.47) increased the odds of discharge against medical advice.
      The odds of such discharge decreased with increasing age (OR 0.994 per year; 95%
      CI 0.990-0.999). The proportion of patients discharged against medical advice
      decreased from 1.4% in 1995 to 0.4% in 1998. The average length of stay decreased
      from 1995 to 1998, with the exception of the Plastic Surgery unit. A
      retrospective review of the charts of 45 patients discharged against medical
      advice (AMA) within 48 hours from admission ascertained some of the stated
      reasons for discharge. Personal and family problems or refusal of treatment were
      reported for 35% of the patients. Of the 25 patients who gave no reasons, 11
      asked again for hospitalization and 5 of these were rehospitalized by IDI within
      10 days. This study also identified that the information on the medical record of
      patients who left against medical advice was generally poor. A standardized form
      for AMA discharges, including patient's understanding of the diagnosis,
      treatment, alternative therapies, consequences of refusing treatment and stated
      reasons for leaving against medical advice, might be of benefit to patients,
      physicians and hospital managers.

PMID- 11235510
TI  - [Microbiological quality of the Catania coastal sea water].
AB  - This study was carried out from 1997 to 1998 along a selected coastal area near
      Catania to ascertain bacteriological and virological quality of marine waters. 44
      seawater samples, collected from 4 stations, were assayed for the presence of
      total and fecal coliforms, fecal streptococci, coliphages, Salmonellae and
      enteric viruses. Two stations localized at canal outfalls showed high levels of
      fecal pollution. The other stations were of good microbiological quality and
      showed a limited number of samples exceeding the standards laid down as guide
      values for bathing waters by Italian normative during the bathing period.
      Salmonellae were isolated in 8 out of 44 sea water samples (18%). Their presence
      was ascertained mainly in samples of the two polluted stations. Enteroviruses
      were not isolated. Enteric viruses such as Reoviruses were isolated from all
      stations, in 12 out of 44 samples (27%). The presence of these viruses was
      ascertained only during autumnal and winter seasons. The results of this study
      showed that, notwithstanding some stations showed high levels of bacteriological
      indicators of fecal pollution and presence of Salmonellae, enteroviruses growing
      on cell cultures were not isolated. Reoviruses confirmed their high diffusion in
      marine waters.

PMID- 11235509
TI  - [Heavy metals: soil characteristics and methods of evaluating parameters for
      defining "contaminated soils"].
AB  - The excessive content of toxic elements in the human environment is associated
      with the etiology of a number of diseases. Soils' pollutants decontamination
      regards the main industrialised countries. Heavy metals represent the main
      problem for soil pollution characterisation. The first approach for pollution
      evaluation is the determination of total metal concentration; the evaluation of
      their bioavailability is required for a correct knowledge of the environmental
      risk. In the present work is shown the procedure to evaluate the sites, which
      require decontamination and which need the following data: knowledge of the
      threshold for each metal in the soil and its range, chemical analysis of the
      components, determination of bioavailability and soil destination. The
      bioavailability is easily calculated by the procedure of aimed extractions.

PMID- 11235511
TI  - Evaluation of near-refraction after administration of ibopamine 2%.

PMID- 11235512
TI  - Ocular pressure increase by ibopamine discloses aqueous humour outflow changes in
      normal tension eyes.

PMID- 11235513
TI  - Ibopamine test in healthy and glaucomatous eyes: tonometric and pupillographic
      study.

PMID- 11235514
TI  - The glaucoma mystery from ancient times to the 21st century. The glaucoma
      mystery: ancient concepts.

PMID- 11235515
TI  - Deficit-undamaged visual field area monitoring in glaucomatous patients with
      advanced perimetric damage: its usefulness.
AB  - This report contains the observations of the authors on the behaviour with time
      of the visual field areas (VF) which appear undamaged by deficit within the
      perimetric findings where at the same time there is advanced glaucomatous damage.
      A retrospective study has been made on the records of a Humphrey perimeter 640
      VFA relating to glaucomatous patients with these perimetric characteristics in
      whom at least 12 examinations (programme "Central 30-2 threshold test") had been
      made and who, for a good part of the period of observation at least, had recorded
      a topographic stability of the deficits. There were found 12 series of
      examinations responding to the required necessities. The analysis of the findings
      used a method that separated from the global mean deviation (MD) that part
      concerning the pathological area and that referring to the "healthy" area of the
      visual field (VF). In 7 of the 8 cases where, at a certain point in the follow
      up, there became evident a trend towards worsening, there was also a significant
      increase in the MD of the undamaged, which occurred before the deterioration of
      the "healthy" area became evident by the appearance of "probability symbols" in
      the "total deviation" map. In the 4 cases where there was stability with time,
      the MD values relating to the undamaged area of the VF were quite constant with
      time.

PMID- 11235516
TI  - The role of frequency doubling technology (FDT) in glaucoma screening.

PMID- 11235517
TI  - Frequency doubling technology and Octopus visual field.

PMID- 11235518
TI  - Comparison between results obtained with traditional perimetry and those with
      frequency doubling perimetry in initial phase chronic simple glaucoma.

PMID- 11235519
TI  - Different value scales between frequency-doubling technique and standard
      threshold perimetry.

PMID- 11235520
TI  - Morphometric differences between optic discs in high tension and normal tension
      glaucomas.

PMID- 11235521
TI  - Topographic sector-by-sector analysis of the optic nerve head by HRT and
      correlation with frank glaucoma perimetric indices.

PMID- 11235522
TI  - Correlation between optic nerve fibre polarimetry and automated perimetry in
      primary open-angle glaucoma.

PMID- 11235523
TI  - Haemorrheological factors and glaucoma.

PMID- 11235524
TI  - Correlation between glaucoma and vascular factors, and circumstances leading to
      the diagnosis of glaucoma.

PMID- 11235525
TI  - Study of optic nerve head perfusion in glaucomatous patients by color Doppler
      imaging with a contrast agent.

PMID- 11235526
TI  - Ocular haemodynamics and nitric oxide in normal pressure glaucoma.
AB  - The authors studied the ocular haemodynamics by means of the Color Doppler
      Imaging (CDI) technique and the levels of cyclic guanosine monophosphate (cGMP),
      the intracellular mediator of NO action in plasma and the aqueous humour in a
      Normal Pressure Glaucoma group and in a normal group. They found significant
      alterations of both the velocities, systolic and diastolic, in the Ophthalmic
      Artery and lower cGMP levels in NPGs than in the controls. These data suggest
      that a disorder of NO regulation processes might be involved in blood supply to
      the optic nerve and in aqueous humour outflow.

PMID- 11235527
TI  - The influence of oestrogen on the pulsatile ocular blood flow.

PMID- 11235528
TI  - Blood circulation and morphology of optic nerve head in primary open-angle
      glaucoma.

PMID- 11235529
TI  - Discriminating between early glaucoma and ocular hypertension: diagnostic
      accuracy of pattern electroretinogram and confocal scanning laser optic disc
      morphometry.

PMID- 11235530
TI  - Corneal thickness in glaucoma: an important parameter?
AB  - Central corneal thickness was measured by pachometry in 49 patients with primary
      open-angle glaucoma (POAG), 41 with ocular hypertension (OHT), 14 with normal
      tension glaucoma (NTG) and 48 normal subjects. The mean corneal thickness of the
      OHT patients was significantly greater than that of the normal control group. The
      NTG patients, on the other hand, had a cornea on average thinner than the
      normals. These differences may cause misclassification of normals with a thick
      cornea as ocular hypertensive eyes or, contrarywise, cause those normals whose
      IOP is underestimated because of a thin cornea to be classed as NTG patients.

PMID- 11235531
TI  - Quantitative mapping of the retinal thickness at the posterior pole in chronic
      open angle glaucoma.
AB  - The sensitivity of a new device, which is able to measure the thickness of the
      retina at the posterior pole (Retinal Thickness Analyzer), was assessed in a
      group of 21 glaucomatous patients, and in 24 patients with ocular hypertension.
      The specificity of RTA was evaluated in a control group of normal eyes. Of the
      glaucomatous eyes, 57.6% had a significant reduction in retinal thickness, while
      another 30.3% were borderline. In the ocular hypertension group, 37.5% of eyes
      were abnormal, and 45.8% were borderline. In the control group, no eye was
      abnormal, though 42.9% had borderline alterations. In many glaucomatous eyes
      (81.8%) there was a relationship between retinal thickness loss and visual field
      defects.

PMID- 11235532
TI  - Ocular hypertension: 12 years' follow-up.
AB  - A retrospective 12-year study on 35 patients having IOP values higher than 21
      mmHg in repeated tonometric curves with no clinical glaucomatous-type signs was
      carried out with the aim of discovering the incidence of the eyes which evolved
      towards the glaucomatous disease, to evaluate the role of the preventive therapy
      and to observe how response to the ibopamine provocation test (which assesses
      outflow pathway compromission) was modified with time. The data obtained showed
      that, in 39.13% of the eyes, there was an evolution towards the disease. The
      ibopamine test was positive at time "0" (study begins) in 48.14% in the evolutive
      eyes and in 66.66% of the eyes which remained stable, while, at time "12" (study
      ends), almost all of the eyes (92-95%) had become positive. The role of
      precociously initiated ocular hypotensive therapy concurring with the test
      positivity is put in evidence.

PMID- 11235534
TI  - Comparison of the efficacy on intraocular pressure and retinal blood flow of a
      beta-blocker (timolol maleate) against the fixed association of a topical
      carbonic anhydrase (dorzolamide) and a beta-blocker (timolol maleate).

PMID- 11235533
TI  - The hypotensive efficacy of dorzolamide HCL-timolol maleate 0.50% vs concomitant
      use of the two drugs.

PMID- 11235535
TI  - Hypotensive efficacy in primary open-angle glaucoma and ocular hypertension:
      latanoprost in monotherapy vs timolol and dorzolamide in association.

PMID- 11235536
TI  - Evaluation and comparison between the effects on intraocular pressure and retinal
      blood flow of two antiglaucomatous drugs administered in monotherapy: brimonidine
      and latanoprost. Preliminary results.

PMID- 11235537
TI  - Latanoprost 0.005%: evaluation of its effect on accommodative capacity.

PMID- 11235538
TI  - The role of the uveoscleral outflow in the management of pigmentary glaucoma: a
      24-month study comparing latanoprost with timolol.

PMID- 11235539
TI  - Preliminary results of a study of the follow-up of nine glaucomatous patients
      treated with preservative-free eye drops.

PMID- 11235540
TI  - The protective effect of citicoline on the progression of the perimetric defects
      in glaucomatous patients (perimetric study with a 10-year follow-up).

PMID- 11235541
TI  - A retrospective study on the effects of laser trabeculoplasty in open-angle
      glaucoma: a 10-year follow-up.

PMID- 11235543
TI  - Comparison between deep sclerectomy with reticulated hyaluronic acid implant and
      trabeculectomy in glaucoma surgery.

PMID- 11235542
TI  - Combined phacoemulsification and deep sclerectomy vs phacoemulsification and
      trabeculectomy.

PMID- 11235544
TI  - Efficacy of sulodexide as adjunct in trabeculectomy. A two-year randomized
      clinical study.

PMID- 11235545
TI  - Post-trabeculectomy hypotension and hypoathalamia: efficacy of treatment with
      ibopamine eyedrops.

PMID- 11235546
TI  - Experimental ocular acute hypertension-induced chromatinic alterations in
      astrocytic cells in rat optic nerve.
AB  - The effects of ocular acute hypertension experimentally induced on the astrocyte
      cells of rat have been studied. Evaluation was made of the damage to the
      chromatin of those cells by means of cytochemical (haematoxylin-eosin) analysis
      and of the state of fragmentation of the DNA by means of the TUNEL technique as
      well as the protective effect of the peroxide scavenger, troxol, on those events.

PMID- 11235547
TI  - Pseudoexfoliatio capsulae and endothelin-1 plasma levels.
AB  - The authors found an increase of endothelin-1 (ET-1) plasma levels in patients
      with pseudoexfoliatio syndrome (PXS): 2.730 +/- 0.224 pg/ml vs 1.420 +/- 0.30S
      pg/ml. With Color Doppler Imaging (CDI) they found in PXS patients a decrease of
      peak systolic velocity values in the posterior ciliary arteries that were 12.725
      +/- 2.536 cm/sec vs 15.450 +/- 3.173 cm/sec (p < 0.049) while the resistance
      values were increased 0.640 +/- 0.051 vs 0.548 +/- 0.058 (p < 0.001). The
      increase of ET-1 plasma levels may assess the vasospasm and uveal tissue hypoxia.

PMID- 11235548
TI  - The ibopamine test in patients affected by monolateral pseudoexfoliative
      glaucoma.

PMID- 11235549
TI  - Health risks during travel: a population-based study amongst the Hong Kong
      Chinese.
AB  - Between June 1998 and October 1998, a cross-sectional survey was carried out in
      Hong Kong on 369 Chinese residents who had travelled to mainland China or
      elsewhere overseas in the previous 12 months. The aim was to collect data on
      which intervention strategies to minimise travel-related illness among the public
      might be based. In interviews by telephone, information on travel-related health
      problems, factors related to such problems, and barriers in the acquisition of
      travel-health advice was gathered using a structured, pre-tested questionnaire.
      Most of the subjects had travelled to countries in the Asia-Pacific region, with
      mainland China as the most popular destination (44%), followed by Thailand (14%).
      Overall, 16% of the respondents had developed health (mainly alimentary and
      respiratory) problems during or after their travel, 8% had received pre-travel
      health advice but 59% reported taking some form of precaution against travel
      related illness. Although only 12% had lost at least a day of work or travel
      because of their travel-related health problems, 40% perceived themselves at risk
      of future travel-related illness, and 68% said they were willing to pay for the
      prevention of travel-health problems. Younger travellers and those who perceived
      relatively few health risks in future travel were relatively more likely to have
      developed health problems. There appears to be a clear need to develop
      appropriate health-promotion strategies to reduce travel-health risks among the
      residents of Hong Kong and the rest of the Asia-Pacific region.

PMID- 11235550
TI  - Malaria during pregnancy and infancy, in an area of intense malaria transmission
      in central India.
AB  - The clinico-epidemiological pattern of malarial infection in a cohort of pregnant
      women and infants was analysed during a malaria epidemic (1997-1998). The
      subjects were all members of tribal communities in an isolated and almost
      inaccessible area of central India. Overall, 151 (55%) of the 274 pregnant women
      investigated were found to have malarial infections at some time during the
      study, with Plasmodium falciparum predominating (88% of infections). All of the
      women investigated, whether primigravidae (42% found infected), secundigravidae
      (68%) or multigravidae (54%), were at great risk of developing severe malaria.
      When trimesters were compared, the highest prevalence of P. falciparum infection
      was recorded in the second (59% infected), irrespective of parity. Of the women
      found infected with P. falciparum, 3% had abortions, 4% stillbirths and 2% had
      babies who died while neonates. The small number of P. vivax infections observed
      prevented similar analyses for this species of parasite. Malarial infection was
      also seen in 218 (41%) of the 535 infants investigated. The values of age
      specific prevalences revealed that > 30% of the infants examined at 2 months of
      age were then found to have P. vivax and/or P. falciparum parasitaemias. At 1
      year of age, overall malaria prevalence was 50%, with P. vivax representing 25%
      of the infections and P. falciparum the rest. Subsequent follow-up revealed that
      three of the infants investigated, each of whom had had P. falciparum infections
      previously, died before their first birthdays. Re-infections (or treatment
      failures) were found to be common, both in the infants and the pregnant women.
      Pregnant women and infants from the study area clearly require systematic
      intervention to reduce their malaria-attributable morbidity.

PMID- 11235552
TI  - Resistance of Plasmodium falciparum malaria to chloroquine is widespread in
      eastern Afghanistan.
AB  - After two decades of war and conflict in Afghanistan, the public-health system is
      in disarray and malaria has re-emerged as a major disease, with Plasmodium
      falciparum malaria becoming increasingly common. The limited healthcare services
      that are available are mainly delivered by non-governmental organizations in
      collaboration with the Ministry of Health. Although chloroquine (CQ) remains the
      official first-line treatment against P. falciparum malaria, there is little
      information on the severity or distribution of resistance to this drug in
      Afghanistan. In-vivo surveys, co-ordinated by the Malaria Reference Centre in
      Jalalabad, were therefore performed to determine the frequency and grades of CQ
      resistance in the three eastern provinces of Kunar, Nangarhar and Laghman. Of the
      142 cases enrolled in the study, only 47 (33%) were sensitive. Most of the cases
      (55%) showed RI resistance but RII/RIII resistance was not uncommon (11%). The
      prevalence of resistance appeared similar in children and adults, in males and
      females, and in each of the three provinces investigated. Gametocyte carriage
      post-treatment was elevated in the resistant cases. As in neighbouring Pakistan,
      the resurgence of P. falciparum in Afghanistan is probably associated with the
      transmission and spread of chloroquine-resistant strains. The first-line therapy
      used against P. falciparum malaria must be changed in order to reverse this
      trend.

PMID- 11235551
TI  - Immunological alterations associated with Plasmodium vivax malaria in South
      Korea.
AB  - Various haematological and immunological studies on patients infected with
      Plasmodium vivax were undertaken, at diagnosis (day 0), after treatment with
      chloroquine but during primaquine treatment (day 10) and after all treatment (day
      59), in South Korea (where there has been a recent and abrupt increase in the
      incidence of such infection). The main aims were to gain an understanding of the
      haemto-immunological alterations of this malarial infection, both before and
      after treatment, and to identify at least one useful marker for the diagnosis and
      post-treatment monitoring of P. vivax malaria. Thirty-eight patients with P.
      vivax malaria were compared with 20, apparently healthy controls. At diagnosis,
      the patients had lymphopenia, marked eosinopenia (the eosinophil count being
      correlated with the platelet count) and thrombopenia. Cells of most of the
      lymphocyte subsets investigated [i.e. CD3+, CD8+, CD19+, CD56+, CD3-/CD56+ and
      CD8+/CD56+ but not CD4+, CD3+/CD56+ or CD25+] were significantly less common
      among the lymphocytes of patients at diagnosis than among those of the controls.
      After initiating treatment, the numbers of CD19+ lymphocytes gradually increased
      (to normal values by day 59), whereas those of CD3+/56+ lymphocytes remained
      abnormally low throughout the follow-up period. The proportions of lymphocytes
      identified as CD4+ appeared to be unaffected by treatment. Although serum
      concentrations of IgE (and, to a lesser extent, IgM) were elevated in the
      patients at diagnosis, they were subnormal on day 10 post-treatment and normal at
      the day-59 follow-up. Serum concentrations of IgG and IgA in the patients were
      always found to be similar to those in the controls. At diagnosis the serum
      concentrations of complements C3 and C4 were significantly elevated in the
      patients. C3 remained at the same high concentration during follow-up but the
      concentration of C4, like that of IgE, was found to be subnormal on day 10 and
      normal 7 weeks later. The level of parasitaemia (%) was only found to be
      significantly correlated with haemoglobin concentration. The observation of
      eosinopenia with elevated IgE and C4 could be a useful indicator of P. vivax
      malaria, and treatment response could be followed by serial monitoring of serum
      concentrations of IgE and C4.

PMID- 11235553
TI  - In-vivo antimalarial activity of Cassia occidentalis, Morinda morindoides and
      Phyllanthus niruri.
AB  - The ethanolic, dichloromethane and lyophilized aqueous extracts of Cassia
      occidentalis root bark, Morinda morindoides leaves and whole plants of
      Phyllanthus niruri were evaluated for their antimalarial actvity in vivo, in 4
      day, suppressive assays against Plasmodium berghei ANKA in mice. No toxic effect
      or mortality was observed in mice treated, orally, with any of the extracts as a
      single dose, of 500 mg/kg body weight, or as the same dose given twice weekly for
      4 weeks (to give a total dose of 4 g/kg). No significant lesions were observed,
      by eye or during histopathological examinations, in the hearts, lungs, spleens,
      kidneys, livers, large intestines or brains of any mouse. At doses of 200 mg/kg,
      all the ethanolic and dichloromethane extracts produced significant
      chemosuppressions of parasitaemia (of > 60% for C. occidentalis root bark and Ph.
      niruri whole plant, and of 30% for M. morindoides leaves) when administered
      orally. The most active ethanolic extract, that of Ph. niruri, reduced
      parasitaemia by 73%. The dichloromethane extracts of M. morindoides and Ph.
      niruri produced similar reductions (74% and 72% chemosuppression, respectively),
      whereas that of C. occidentalis was slightly less active (60% chemosuppression).
      Each lyophilized aqueous extract was less active than the corresponding ethanolic
      extract.

PMID- 11235554
TI  - Influence of lysates of the salivary glands of Lutzomyia longipalpis on the
      development of a Leishmania-major-like parasite in the skin of the golden
      hamster.
AB  - Twelve years ago, some mice inoculated with Leishmania major were found to
      develop larger lesions, containing more amastigotes, if the inoculum used to
      infect them contained a lysate of salivary glands from Lutzomyia longipalpis than
      if no lysate was included. In the present study, outbred golden hamsters
      (Mesocricetus auratus) were each inoculated in a footpad with 10(4), 10(5), 10(6)
      or 10(7) stationary-phase promastigotes of a Leishmania-major-like parasite
      (MHOM/BR/71/BH49). Some of the inocula used each contained a lysate of the
      salivary glands from a laboratory-reared, female Lu. longipalpis. Only the
      hamsters inoculated with 10(7) promastigotes each developed macroscopic cutaneous
      lesions (all 10 co-inoculated with lysate but only two of the 10 co-inoculated
      with diluent). Each of the lesions developed into cutaneous nodule affecting the
      dermis and underlying subcutaneous tissue of the inoculated footpad, with,
      histologically, an intensive, diffuse and productive, inflammatory reaction.
      There were no apparent differences between the lesions of hamsters infected with
      inocula containing salivary-gland lysate and those seen in the animals infected
      with lysate-free inocula. Future studies will follow the histological changes at
      the sites of Lu. longipalpis bites.

PMID- 11235555
TI  - Frequency distributions of Echinococcus granulosus and other helminths in stray
      dogs in Tunisia.
AB  - The intestinal helminths infecting stray dogs were investigated in the Testour
      and Bouzid regions of Tunisia. Overall, 21% of the dogs necropsied were found to
      be infected with Echinococcus granulosus. The prevalence among the animals from
      Testour (27.0%) was significantly higher than that in the dogs from Bouzid
      (6.9%). Although the prevalence of this species in the dog populations did give a
      significant fit to the age-prevalence models reported earlier, the best fit was
      not consistent with the known biological parameters of the parasite. The
      frequency distribution of E. granulosus was highly aggregated, with a mean
      abundance of infection of 538 parasites/host and a mean intensity in infected
      animals of 2534 parasites/host. Several Taenia species were also found in the
      dogs, but none of these showed evidence of an aggregated distribution and the
      frequency distribution of each fitted a Poisson distribution, which is unusual
      for naturally acquired infections. All the other cestode species and the nematode
      species encountered had aggregated distributions in the dogs. As there was
      relatively little correlation between the worm burdens of the different parasite
      species in the dogs, individual dogs may not be generally susceptible or
      resistant to intestinal helminths of several species.

PMID- 11235556
TI  - Clinical characteristics and disposition kinetics of the hepatomegaly associated
      with acute, uncomplicated, Plasmodium falciparum malaria in children.
AB  - The clinical characteristics and the kinetics of the disposition of the
      hepatomegaly associated with acute, uncomplicated Plasmodium falciparum malaria
      were investigated in 162 children in an endemic area of Nigeria. Hepatomegaly was
      significantly more common in the younger than in the older children. Complete
      resolution occurred in 48% following antimalarial chemotherapy. In the children
      in whom hepatomegaly did not resolve, a reduction in liver size of < 17% by the
      time parasitaemia was cleared (usually on day 3) was associated with non
      resolution of hepatomegaly by days 7 or 14 of follow-up. An increase in liver
      size to at least 125% of the baseline value by day 4 or 5 was associated with a
      lack of therapeutic response, providing the child involved was aged < 5 years. In
      the children who had complete clearance of parasitaemia and resolution of
      hepatomegaly, there was no significant relationship between the parasitaemia
      derived conventional indices of therapeutic response [i.e. time to clearance of
      50% (PC50) or 90% (PC90) of the parasitaemia, and the parasite-clearance time
      (PCT)] and the corresponding parameters derived from measurement of liver size
      [i.e. time for resolution of 50% (HR50) or 90% (HR90) of the hepatomegaly and the
      hepatomegaly-resolution time (HRT)] in the same patients. However, as the
      HR50:PC50, HR90:PC90 and HRT:PCT ratios were similar (range = 1.6-2.1), the liver
      parameters may have therapeutic application. In the children with drug-sensitive
      P. falciparum infections and in whom hepatomegaly completely resolved, the area
      produced by plotting liver size against time (i.e. the area under the curve of
      hepatomegaly v. time, or AUChp) increased in proportion to the liver size below
      the costal margin (P = 0.02, from analysis of variance), but there was no
      significant difference in the half-lives of hepatomegaly (t1/2hp) or in the
      ratios of liver size to AUChp, indicating that the kinetics of the resolution of
      hepatomegaly were linear in the range examined. Comparison of the kinetic indices
      of hepatomegaly and parasitaemia showed that, although the half-lives of
      parasitaemia and hepatomegaly and the corresponding clearance values were
      similar, there was no correlation between these parameters among those in whom
      hepatomegaly completely resolved and parasitaemia completely cleared. These
      results indicate that routine clinical measurement of the liver size in children
      with hepatomegaly during acute, uncomplicated, P. falciparum malaria may have
      some use in evaluating and monitoring the therapeutic responses of infections.
      The resolution of hepatomegaly, a reflection of pathological changes, lags behind
      clearance of parasitaemia in children with P. falciparum malaria, and supports
      the use of the liver 'rate' as a malariometric index for assessing the intensity
      of transmission in endemic areas.

PMID- 11235557
TI  - Community-directed treatment: the way forward to eliminating lymphatic filariasis
      as a public-health problem in Ghana.
AB  - The elimination of lymphatic filariasis as a public-health problem is currently
      dependent on the delivery of annual drug treatments to at least 80% of the
      eligible members of endemic populations for at least 5 years. However, for
      various reasons, this goal may not be achievable by the health systems of most
      endemic countries in sub-Saharan Africa, particularly if treatment is not
      community-directed. In Ghana, community-directed ivermectin treatment involving
      the regular public-health services at the implementation level (ComDT/HS) has
      recently been compared with mass-treatment in which only the health services
      participated (HST). Health staff and the target communities appreciated the
      ComDT/HS approach more than the HST approach and were more willing to participate
      in the community-directed scheme. The treatment coverage achieved by ComDT/HS
      (74.5%) was not only much higher than that of HST (43.5%) but also probably
      adequate for filariasis elimination. HST coverage was particularly poor in
      villages located > 5 km from a health facility, but distance from such a facility
      had no significant effect on treatment coverage in the ComDT/HS arm. As virtually
      all the subjects who received drugs swallowed them, compliance with treatment was
      not a problem. The ComDT/HS approach is therefore recommended, especially for
      areas where access to health facilities is poor and the health workers are over
      stretched. The implications of these findings for the global programme for
      filariasis elimination are discussed.

PMID- 11235558
TI  - The effect of albendazole on Oesophagostomum bifurcum infection and pathology in
      children from rural northern Ghana.
AB  - Ultrasonography has already revealed that up to 50% of individuals in some
      villages in northern Ghana have colonic pathology induced by Oesophagostomum
      bifurcum. Approximately 2% of those affected progress to clinical
      oesophagostomiasis if left untreated. In the present study, ultrasound-positive
      children living in a heavily infected community were each given 5 days of
      treatment with albendazole (10 mg/kg.day), early in the dry season. Treatment
      reduced the prevalence, number, size and half-life of the ultrasound-visible
      nodules, stopped the excretion of O. bifurcum eggs, and reduced the development
      of clinical oesophagostomiasis during the subsequent 8 months. However, the
      treatment had no impact on the new infections that occurred during the following
      rainy season, and no impact on nodule prevalence by the end of that rainy season.
      Surgical management may not be essential in non-acute cases of clinical
      oesophagostomiasis, as albendazole may kill the nodule-dwelling worms.

PMID- 11235559
TI  - Tick-bite-induced anaphylaxis in Spain.
AB  - Although there are very few reports of human anaphylaxis induced by tick bites,
      two such cases have recently been seen in Salamanca, Spain. To identify the tick
      species responsible, salivary-gland extracts from six species of hard tick and
      two of soft tick were prepared and used as allergens/antigens in skin-prick tests
      and serological analyses. For each case, the results of the skin tests were
      positive for several species of hard tick but negative for the soft ticks. ELISA
      and western blots revealed high titres of IgG against hard ticks (but not soft
      ticks) in the sera from both cases. However, serum from only one of the cases was
      found to be ELISA- and western-blot-positive for tick-specific IgE. Accordingly,
      the anaphylaxis seen in one case was IgE-mediated whereas that in the other case
      appeared to be IgE-independent. In both cases, most of the tick-specific
      antibodies only recognized carbohydrate epitopes. High levels of cross-reactivity
      between the salivary-gland extracts from several species of hard tick made it
      impossible to identify which species was responsible for each anaphylactic
      reaction, although the immunological results seem to point to Ixodes ricinus.

PMID- 11235560
TI  - [E-selectin mediates early adhesion of HepG2 hepatoma cells to endothelial
      cells].
AB  - OBJECTIVE: To study the role of E-selectin and sLe(x) in the adhesion between
      hepatoma cells (HepG2) and endothelial cells, and to select drugs capable of
      inhibiting such adhesion. METHODS: HepG2 cells were vitally stained with
      fluorescent dye BCECF-AM. Adhesion between the fluorescent HepG2 cells and human
      umbilical vein endothelial cells (HUVEC) was examined by solid phase adhesion
      assay in vitro. A number of agents were tested for their effect on the tumor cell
      endothelial adhesion. RESULTS: sLe(x) on the surface of HepG2 cells and E
      selectin expressed on the surface of HUVEC were necessary for early adhesion.
      HepG2 cells could activate HUVEC to increase their adhesiveness to HepG2 cells.
      Dexamethasone, phenylarsenic oxide, levamisole and actinomycin D were able to
      block the adhesion between HepG2 to HUVEC at low concentrations. CONCLUSION:
      sLe(x) and E-selectin are important molecules in the early adhesion of hepatoma
      cells to HUVEC. Cytokine-like factors of HepG2 origin are likely involved in the
      activation of endothelial cells in the target tissue. Agents capable of
      inhibiting NF kappa B can be hopefuly used as anti-adhesion drugs to inhibit
      metastasis of liver cancer.

PMID- 11235561
TI  - [The role of bcl-2 gene family in taxol-mediated apoptosis in BJAB B cell
      lymphoma cell line].
AB  - OBJECTIVE: To study the apoptosis-inducing effect of taxol on BJAB B cell
      lymphoma cell line and the role of bcl-2 gene family. METHODS: BJAB cells were
      treated with taxol and examined for morphologic changes under light and electron
      microscopes. Flow cytometry assays and DNA gel electrophoresis were used to
      demonstrate changes in nuclear DNA contents and DNA fragmentations. Changes in
      bcl-2 gene family at mRNA and protein levels were studied by immunohistochemistry
      and semi-quantitative RT-PCR technique. RESULTS: Taxol inhibited growth of BJAB
      cells. The cells initially showed G2/M arrest, followed by apoptosis, in a time
      and dose dependent manner. The expression of bcl-2 at mRNA and protion level was
      decreased while that of bcl-xs transcription was increased after taxol treatment.
      CONCLUSION: Taxol induces apoptosis of BJAB cells. Bcl-2 and bcl-xs are involved
      in the regulation of taxol-induced apoptosis.

PMID- 11235562
TI  - [Protection of hematopoietic cells against toxicity of anticancer agents by
      transfecting mdr1 gene into bone marrow cells].
AB  - OBJECTIVE: To investigate whether the hematopoietic cells can be protected from
      the toxic effect of anticancer agents by transfecting mdr1 gene into bone marrow
      cells. METHODS: The mdr1 gene was transfected into murine and human bone marrow
      cells by Lipofectin. Expression of mdr1 was assessed by RT-PCR and flow
      cytometry. The functional activity of mdr1 in transfected cells was examined by
      rhodamine retention assay. Resistance to chemotherapeutic drugs of human and
      murine mdr1 gene transfected bone marrow cells was ascertained in vivo and that
      of murine cells was assessed in vivo in a bone marrow transplantation model.
      RESULTS: Multidrug resistance 1 gene was successfully transfected into and
      expressed in murine and human bone marrow cells. The transfected cells were
      resistant to doxorubicin; Vp-16, vincristine and colchicine. Bone marrow cells
      transfected with mdr1 gene reconstituted the hematopoietic function and offered
      resistance to doxorubicin in recipient mice. CONCLUSION: To transfect mdr1 gene
      into bone marrow cells is a promissing approach to protect bone marrow cells from
      the myelosuppressive effect of chemotherapeutic agents.

PMID- 11235563
TI  - [Identification of a new molecular marker related to tumorigenesis of the stomach
      and small intestine].
AB  - OBJECTIVE: Screening and identification of molecular markers associated with
      tumorigenesis of the gastrointestinal tract. METHODS: Techniques of random
      amplified polymorphic DNA (RAPD), restriction fragment length polymorphism
      (RFLP), Southern blot and Northern blot, gene cloning and sequencing were
      employed to reveal new molecular markers from tumors of different origins.
      RESULTS: Of 32 RAPD fragments possibly associated with tumorigenesis, 29 were
      cloned into pCAPs vector. Further analysis by Southern blot revealed that the
      majority of the cloned fragments was repetitive sequences. Among the remaining
      single-copy fragments, one was found deleted in malignant tumors of the stomach
      and small intestine. It did not hybridize with mRNA extracted from blood
      lymphocyte and cultured fibroblasts. Sequence analysis indicated that this single
      copy fragment contained a motif similar to eukaryotic cis-acting "CACA" box
      promoter. At its downstream there was an "ATG" transcription activator codon. No
      homologous sequence was found in the GenBank and it was therefore accepted by the
      GenBank. (Accession Number: AF151005). CONCLUSION: A single-copy fragment
      containing cis-acting "CACA" box has been identified, which might be the upstream
      of a new tumor suppressor gene deleted in tumors of the stomach and small
      intestine.

PMID- 11235564
TI  - [Correlation study of TGF beta expression in diethylnitrosamine-induced rat liver
      cancer and mast cells in its vicinity].
AB  - OBJECTIVE: To study the correlation between tumor cell expression of TGF beta and
      the amount of surrounding mast cells in hepatocarcinogenesis. METHODS:
      Hepatocarcinoma was induced by diethylnitrosamine (DENA) in rats. The expression
      of TGF beta was examined immunohistochemically, and mast cells were identified by
      Alcian blue staining. The results were undergone cell imaging analysis. RESULTS:
      Positive expression of TGF beta was observed in the cytoplasm of the
      hepatocarcinoma cells. The intensity of expression differd in various groups of
      experiment. There was a positive correlation between the intensity of the TGF
      beta expression in hepatocarcinoma cells and the amount of mast cells surrounding
      the tumor nodules (P < 0.01). CONCLUSION: Mast cell infiltration in DENA-induced
      rat hepatoma may be due to the chemotactic effect of TGF beta expressed in tumor
      cells.

PMID- 11235565
TI  - [Bcl-2 anti-sense oligonucleotide sensitizes Fas-mediated apoptosis of gastric
      cancer cells].
AB  - OBJECTIVE: To study the effect of bcl-2 anti-sense oligonucleotide on the
      sensitivity of gastric cancer cells to Fas-mediated apoptosis. METHODS: Gastric
      cancer cell line MKN45 was transfected with bcl-2 anti-sense oligonucleotide, and
      expression of bcl-2 was examined by Western blotting. Agonistic Fas antibody was
      used to induce apoptosis detected by TUNEL staining and flow cytometry. RESULTS:
      Bcl-2 expression in MKN45 cells transfected with bcl-2 anti-sense oligonucleotide
      was markedly inhibited. When cultured with antibody apoptosis index of the anti
      sense oligonucleotide-treated MKN45 cells was 55.6% +/- 4.7% (n = 5), which was
      significantly higher than that of the control (8.4% +/- 2.1%, n = 5). CONCLUSION:
      Expression of bcl-2 in gastric cancer cells may antagonize Fas-mediated
      apoptosis.

PMID- 11235566
TI  - [Correlation between methylation on SmaI locus of the CDKN2/p16 gene CpG island
      and lung cancer].
AB  - OBJECTIVE: To study the relationship between the status of methylation of the
      CDKN2/p16 gene 5'-CpG island and lung cancer. METHODS: Genomic DNA was digested
      with methylation-sensitive enzyme SmaI and Southern blotting was applied to
      analyze the status of methylation of the CDKN2/p16 in 89 cases of lung cancer and
      10 cases of normal lung tissue. RESULTS: Of the 89 cases of lung cancer studied,
      the CDKN2/p16 gene was shown to be methylated in 15 cases (16.9%). It occurred in
      12 of 42 p16 protein negative cases (28.6%), and in 3 of 47 p16 protein positive
      cases. The CDKN2/p16 gene was not shown to be methylated in 10 cases of normal
      lung tissue. CONCLUSION: Methylation of the CDKN2/p16 gene 5'-CpG island may be
      an important mechanism for gene inactivation in lung cancer progression.

PMID- 11235567
TI  - [Expression of beta 2 integrins and L-selectin on CML cells after treatment with
      IFN-alpha and allo-bone marrow transplantation].
AB  - OBJECTIVE: To study the expression of L-selectin, Mac-1, LFA-1 on CML progenitor
      cells in relation to CML progression and therapeutic effect. METHODS: The
      expression of adhesion molecules (LFA-1, Mac-1, L-selectin) on bone marrow CD34+
      cells from 34 CML patients were analyzed by three-color flow cytometry. RESULTS:
      The mean percentage of expression of L-selectin, and LFA-1 on CD34+ CD38-(-)+
      cells from untreated CML patients was significantly lower than that from normal
      controls. Among 8 CML patients treated with IFN-alpha, the expression of L
      selectin and LFA-1 on CD34+ CD38- cell (37.6 +/- 5.3%, 42.1 +/- 13.1%) was
      comparable to that from normal controls (38.2 +/- 9.4%, 48.2 +/- 12.2%). L
      selectin expression in CD34+ CD38- cells from CML patients was inversely
      correlated with the percentage of Ph'(+) cells. In 2 CML patients treated with
      allo-bone marrow transplantation, the expression rate of L-selectin, IFA-1 and
      Mac-1 on CD38+ CD38- cells was comparable to that from normal controls.
      CONCLUSION: The data suggest that decreased expression of L-selectin and LFA-1 in
      CML CD34+ cells reflects one of the features of malignant CML progenitors. IFN
      alpha and allo-BMT restore the expression of Mac-1, L-selectin and LFA-1 to
      normal on CML CD34+ cells.

PMID- 11235568
TI  - [Application of fluorescence in situ hybridization (FISH) in sputum cytologic
      diagnosis of lung cancer].
AB  - OBJECTIVE: To study the numerical chromosomal abnormalities of cells in sputum
      from patients with lung cancer by dual-fluorescence in situ hybridization (FISH).
      METHODS: Thirty sputum samples from lung cancer patients were examined by FISH
      with centromere DNA probes of chromosome 7, 11, 17 and X. RESULTS: In 23 positive
      sputum samples studied, the frequency of hyperdiploid of chromosome 7, 17, X and
      11 was 65.2% (15/23), 60.9% (14/23), 52.2% (12/23) and 39.1% (9/23),
      respectively. Hyperdiploidy of chromosome 7 was found in 4 of 7 sputum samples
      which were cytologicaly suspicious of cancer cells. CONCLUSION: FISH can detect
      aneuploid malignant cells in sputum and be used as a complementary technique to
      cytologic diagnosis of lung cancer.

PMID- 11235569
TI  - [Apoptosis and uterine cervical carcinogenesis].
AB  - OBJECTIVE: To investigate the possible role of apoptosis in the development of
      uterine cervical carcinoma. METHODS: Formalin-fixed, paraffin-embedded samples
      from 190 patients [41 patients with severe dysplasia (SD); 37 with carcinoma in
      situ(CIS); 31 with microinvasive carcinoma (MIC), 40 with fran invasive large
      cell non-keratinizing epidermoid carcinoma (IC)], and 41 samples from normal
      cervical squamous epithelium (NE) were studied. The number of apoptotic cells was
      assessed in situ by the TDT-mediated dUTP-biotin nick end labeling (TUNEL)
      method. PCNA, p53 and bcl-2 were demonstrated immunohistochemically. RESULTS: (1)
      In NE, TUNEL-positive cells were found in the superficial layer and PCNA-positive
      cells were confined in the lamina profunda, while in cervical neoplasia these
      cells were irregulasly scattered throughout the cervical lesions. (2) The TUNEL
      staining index decreased while PCNA increased with progression of the neoplasm,
      showing a significant negative correlation between apoptosis and proliferation.
      (3) In patients with SD and CIS who had overexpression of p53 and bcl-2 proteins,
      the cells positively stained by TUNEL were significantly less in number than in
      these with negative p53 and bcl-2 expression. No such observation for PCNA
      expression. CONCLUSION: These results suggest that apoptosis is associated with
      the early process of cervical carcinogenesis and apoptosis is closely correlated
      with overexpression of p53 and bcl-2 proteins.

PMID- 11235570
TI  - [Application of microsatellite alteration of urine sediment in the early
      diagnosis of bladder cancer].
AB  - OBJECTIVE: To assess the usefulness of microsatellite DNA sequence (MS)
      alterations in urine sediment for early diagnosis of human bladder cancer.
      METHODS: Loss of heterozygosity(LOH) and microsatellite instability(MIN) in urine
      sediment from 28 cases of bladder cancer were detected by polymerase chain
      reaction (PCR) with selected primers of 10 microsatellite loci. The peripheral
      blood mononuclear cells and bladder carcinoma cells were used as controls.
      RESULTS: In 24 of 28 bladder cancer patients (85.7%) LOH and MIN were found in
      urine sediment on at least one MS locus. Only in 3 of 28 patients(10.7%) was the
      urine cytology positive while MS and MIN were detected in these 3 patients. The
      conformance of MS alterations between cancer cells and urine sediment in the same
      patients was 94.1%. No MS alteration was found in 15 normal controls. CONCLUSION:
      Application of microsatellite sequence of urine sediment can be considered as a
      new tool for screening and early diagnoses of bladder cancer.

PMID- 11235571
TI  - [Studies of multidrug resistance gene expression and apoptosis in stomach
      carcinoma].
AB  - OBJECTIVE: To investigate the influence of multidrug resistance gene (MDR)
      expression and apoptosis on stomach cancer. METHODS: A total of 80 cases of
      paraffin embedded stomach cancer tissues was stained immunohistochemically for P
      gp, GST-pi and TOPO II using monoclonal antibodies and apoptosis (in terms of
      apoptotic index, AI) in tissues was musured by the TUNEL method. The results were
      correlated with tumor type, clinical stage and prognosis. RESULTS: Normal stomach
      tissue expression of P-gp was associated with better survival, but higher level
      of P-gp expression in tumor tissues was associated with poor prognosis. The
      expression of GST-pi didnot show a relationship with cell differentiation of
      stomach cancer and clinical stage of the disease, but positive correlation did
      exist between intensity of expression and survival time. Although the expression
      of TOPO II was associated with tumor cell differentiation, it did not affect
      prognosis. Apoptosis was demonstrated in 73% of the cases and was related to
      clinical stage of stomach carcinoma. CONCLUSION: While P-gp expression in tumor
      cells is indicative of poor prognosis, its expression in normal tissue has the
      opposite effect. Positive correlation exits between GST-pi expression intensity
      in tumor cells and survival. MDR and apoptosis are related to the biologic
      behavior of the tumor.

PMID- 11235572
TI  - [Expression of bcl-2 gene in relation to histologic type and grade, and prognosis
      of breast cancer].
AB  - OBJECTIVE: To ascertain whether bcl-2 gene expression is related to histologic
      type and grade, and prognosis of breast cancer and its prognosis. METHODS:
      Expression of bcl-2 protein was examined immunohistochemically in 85 cases of
      breast cancer patients with > or = 5 years of follow-up. RESULTS: Expression of
      bcl-2 protein was detectable in 68.2% of breast cancer specimens. It was not
      related to histologic type, but to histologic grade of the cancer. In grade I,
      bcl-2 was positive in 95.2% of the specimens which was significantly higher than
      that in grade II (64.6%) and grade III (25.0%)(P < 0.01). The positive rate of
      bcl-2 expression was 75.9% in patients who survived > or = 5 years as compared to
      that (51.6%) in patients survived < 5 years (P < 0.05). CONCLUSION: Expression of
      bcl-2 occurs more frequently in well differentiated breast cancer. It is
      associated with better prognosis of the patients.

PMID- 11235573
TI  - [Status of methylation of promoter of mis-match repair gene hMLH1 in lung
      cancer].
AB  - OBJECTIVE: To study the relationship between status of methylation of hMLH1
      promoter and expression of its protein in lung cancer. METHODS: Methylation of
      the hMLH1 gene promoter and hMLH1 protein was examined in 50 primary lung cancer
      tissues by Hpa II digestion-PCR and immunohistochemistry. RESULTS: The incidence
      of the hMLH1 promoter methylation was 32.0% (16/50). Methylation frequeney did
      not correlate with sex, smoking and clinicopathological characteristics. Negative
      expression of hMLH1 protein occurred in 14/46 tumors, of which 11 tumors had
      hMLH1 promoter methylation (78.6%, 11/14), while only 5 had methylation in 32
      specimens positive for hMLH1 protein expression. CONCLUSION: In about one-third
      of lung cancer tissues examined there exists methylation of hMLH1 promoter, which
      correlates well with the absence of expression of hMLH1 protein.

PMID- 11235574
TI  - [E-cadherin expression and its clinical significance in cervical cancer].
AB  - OBJECTIVE: To study the clinical significance of E-cadherin (E-CD) expression in
      cervical cancer. METHODS: Specimens of 60 cervical cancer, 10 normal cervical
      epithelia and 12 cervical intraepithelial neoplasia(CIN) were examined for E-CD
      expression by immunohistochemical staining. RESULTS: E-CD was expressed in all of
      10 specimens of normal cervical epithelia. Positive staining was seen in 66.7% of
      CIN, 46.7% of cervical cancer. In cervical cancer, the frequency of abnormal E-CD
      expression was correlated to pathologic grade, lymph node metastasis and clinical
      stage (P < 0.05). The higher the pathologic grade of tumor, the lower was the
      expression of E-CD. Negative E-CD expression was significantly more frequent in
      the advanced stage of cervical cancer with lymph node metastasis. CONCLUSION:
      Decreased expression of E-CD is a useful parameter of cervical malignancy.

PMID- 11235575
TI  - [CT diagnosis of fibrothecoma and fibroma of the ovary].
AB  - OBJECTIVE: To describe the CT characteristics and improve pre-operative diagnosis
      of fibrothecoma and fibroma of the ovary. METHODS: The clinical and CT image
      material of 14 postmenopausal patients with pathologically confirmed fibrothecoma
      or fibroma of the ovary were reviewed. RESULTS: Of the 14 cases, 7 had ascites.
      The tumor was solid in 10 cases, cystic or cystic-solid in 2 cases. It was round
      or elliptic in 9 cases, multilobular or irregular in shape in 5. In all cases,
      the tumors had clear border. On CT imaging, the solid tumor, the solid part of
      the cystic-solid tumor, and the cystic wall were similar in density to that of
      myometrium on precontrast scanning. There was no or slight uptake on postcontrast
      enhancement, the density of which was obviously lower than that of myometrium. In
      tumors heterogeneous in density, low density areas of light flakes or streaks
      were observed. In cystic or cystic-solid tumors, the demarcation between the
      cystic and solid portion was clear. Nodules on cystic wall were visible.
      CONCLUSION: CT is useful in the diagnosis of the fibrothecoma and fibroma of the
      ovary.

PMID- 11235576
TI  - [Treatment of superior vena cava syndrome in cancer patients with intravascular
      stent and local thrombolysis].
AB  - OBJECTIVE: To study the therapentic efficacy of using intravascular stent and
      local thrombolysis for superior vena cava syndrome(SVCS) in cancer patients.
      METHODS: Among 26 cancer patients with SVCS there were 17 cases of lung cancer
      with mediastinal lymphnode metastases, 5 cases of malignant mediastinal tumor, 2
      cases of non-Hodgkin's lymphomas, 2 cases of esophageal carcinoma with
      mediastinal lymphnode metastases. Through femoral vein, a catheter with side
      holes was introduced up to the superior vena cava. Following local dripping of
      urokinase for 20-40 min, the obstructed region was distended with the inflated
      balloon and then a self-expanding stent was put in the inflated region. RESULTS:
      The procedure was successful in 24 patients, but failed in 2 cases because the
      guide wire could not pass through the obstructed region. In 3 patients with
      superior vena cava stenosis of 10 cm in length, two stents were used. In the
      other 21 patients, 1 stent was adequate. Local thrombolytic treatment was given
      in 24 patients before the angioplastic balloon was inflated. The vena caval
      pressure at the distal end of the stenotic lesion dropped from 21.23 +/- 1.80 mm
      Hg before treatment to 5.33 +/- 0.98 mm Hg after treatment. The difference was
      statistically significant. Collateral veins were no longer filled by contrast
      after treatment. The caliber of the supericar vena cava restored to normal and
      its outline was smooth. The symptoms of SVCS subsided after treatment in 2-3
      days. CONCLUSION: Intravascular, self-expandable stent combined with local
      thrombolysis is a micro-invasive and effective method of treatment for cancer
      patients with superior vena cava syndrome.

PMID- 11235578
TI  - [Clinicopathological studies on bone marrow involvement of non-Hodgkin's
      lymphoma].
AB  - OBJECTIVE: To investigate the relationship between pathomorphological features
      and clinical manifestations of non-Hodgkin's lymphoma (NHL) with bone marrow
      involvement (BMI). METHODS: Plastic-embedded section of bone marrow biopsy was
      stained with H-Giemsa-E. Immunotyping of NHL was performed immunohistochemically.
      RESULTS: A total of 70 patients with NHLBMI(male: 52, female: 18; median age: 49
      years) was studied. There were 20 patients with T cell-lymphoma and 50 patients
      with B cell-lymphoma. The extent of bone marrow involvement was minimal in 15
      cases, moderate in 16 cases and severe in 39 cases. Bone marrow involvement was
      of interstitial type in 23 cases, nodular type in 7 cases, and mixed type in 18
      cases and diffuse type in 22 cases. The frequency of splenomegaly in nodular type
      NHLBMI was significantly higher than that in any other type. Nodular type NHLBMI
      occurred mainly in B cell-lymphoma. Lymphoma cell leukemia (LCL) developed in 14
      of 39 (35.9%) cases of NHL with severe bone marrow involvement which was
      significantly more frequent than that in NHL with mild and moderate bone marrow
      involvement. CONCLUSION: Difference in the extent and pattern of bone marrow
      involvement in NHL is related to clinical manifestations. Bone marrow biopsy
      helps evaluate response to treatment.

PMID- 11235577
TI  - [Results of phase III clinical trial of zeng sheng-ping in the treatment of
      patients with esophageal epithelial hyperplasia].
AB  - OBJECTIVE: Through a multi-center randomized, single blinded and placebo
      controlled trial to evaluate the therapentic effect of Zeng Sheng-ping (ZSP) on
      esophageal epithelial hyperplasia in a population with high risk of esophageal
      cancer. METHODS: The residents between 40 and 65 years of age in Ci County of
      Hebei Province were screened by balloon cytological examinations of the
      esophagus. Patients with esophageal epithelial hyperplasia were further confirmed
      by biopsy with esophagoscopy. They were randomly stratified into different arms
      according to sex, age and the grade of hyperplastic lesions. A total of 449 with
      esophageal epithelial hyperplasia were eligible and randomized into ZSP group and
      placebo group. In ZSP group, 300 patients received oral ZSP 8 tablets, twice a
      day for 6 months. There were 149 patients, in the placebo group. To ensure the
      accuracy of the trial, riboflavin was added into ZSP and placebo group as an
      indicator of compliance and urine samples were periodically examined. RESULTS:
      After 6 months of treatment, the response rate was 64.4% (193/300) in ZSP group
      and 22.8% (34/149) in the placebo group. There was a statistically significant
      difference between the two groups(P < 0.001). In addition, the frequency of
      disease progression in ZSP group was 3.3% (10/300) while that in the placebo
      group was 24.8% (P < 0.001). CONCLUSION: ZSP is an effective drug in the
      treatment of esophageal epithelial hyperplasia. Adverse effects are mild and well
      tolerated by the patients.

PMID- 11235579
TI  - [Clinical application of extended resection of Vater's papilla].
AB  - OBJECTIVE: To report the surgical technique and clinical application of extended
      resection of Vater's papilla (ERVP). METHODS: ERVP was performed in 12 selected
      patients with tumors of ampulla of Vater according to the following criteria: (1)
      no signs of distant mestastasis before operation; (2) no hepatic and peritoneal
      mestastasis during exploration, frozen section of peripancreas-duodenal lymph
      nodes being negative; (3) tumor less than 2 cm in diameter, pathologic
      examination of tumor being adenocarcinoma or adenoma; (4) pathologic examination
      of edge of resection being negative. RESULTS: There was no operative death nor
      complications in 12 cases treated by ERVP. The average time of operation was 2.3
      hours, the average amount of blood infused was 433 ml, and the average time of
      hospitalization was 15.8 days. In 5 of 10 cases of Vater's ampullary
      adenocarcinoma, the mean survival time was 42 months (36-62 months). The
      remaining 5 cases are still alive at 20-64 months. Two patients with Vater's
      ampullary adenoma still survive at 32 and 46 months, respectively. CONCLUSION:
      ERVP is easy to perform with comparatively less surgical trauma and complication,
      but redical excision of tumor is not easy. It may be particulary indicated for
      older and high-risk patients, or patients with cancer less than 2 cm in diameter.

PMID- 11235580
TI  - [A clinical analysis of combination treatment with brachytherapy and external
      radiation, plus chemotherapy for the treatment of esophageal cancer].
AB  - OBJECTIVE: To analyse the value of various combinations of treatment for
      esophageal cancer. METHODS: One hundred twenty cases of esophageal cancer were
      randomly divided into four groups, 30 cases in each group. Group I was treated
      with external radiation (RT) alone; group II, with RT plus brachytherapy; group
      III with RT plus chemotherapy, and group IV with RT plus brachytherapy and
      chemotherapy. RT with 60Co was given 2 Gy daily, 5 times a week, with a total
      dose of 60-74 Gy. Brachytherapy was given 6-8 Gy once weekly with a total dose of
      18-24 Gy. Chemotherapy with carboplatin was given 100 mg/day, five days a week at
      first and fifth week. RESULTS: The 1, 2, 3-year survival rate in group II, III
      and IV was higher than that in group I (P < 0.05). The 3-year survival rate of
      group I-IV patients was 13.3%, 36.7%, 40.0%, 46.7%, respectively. More patients
      died of cancer recurrence and progression in group I than in any of the other 3
      groups of patients (P < 0.05). However, the frequency of distant metastasis was
      not significantly different. CONCLUSION: The combination treatment with external
      radiation, brachytherapy and chemotherapy can improve the local control of tumor
      growth and the survival rate in esophageal cancer patients.

PMID- 11235581
TI  - Spatiotemporal QRST cancellation techniques for analysis of atrial fibrillation.
AB  - A new method for QRST cancellation is presented for the analysis of atrial
      fibrillation in the surface electrocardiogram (ECG). The method is based on a
      spatiotemporal signal model which accounts for dynamic changes in QRS morphology
      caused, e.g., by variations in the electrical axis of the heart. Using simulated
      atrial fibrillation signals added to normal ECGs, the results show that the
      spatiotemporal method performs considerably better than does straightforward
      average beat subtraction (ABS). In comparison to the ABS method, the average QRST
      related error was reduced to 58 percent. The results obtained from ECGs with
      atrial fibrillation agreed very well with those from simulated fibrillation
      signals.

PMID- 11235582
TI  - Automatic differentiation of multichannel EEG signals.
AB  - Intention of movement of left or right index finger, or right foot is recognized
      in electroencephalograms (EEGs) from three subjects. We present a multichannel
      classification method that uses a "committee" of artificial neural networks to do
      this. The classification method automatically finds spatial regions on the skull
      relevant for the classification task. Depending on subject, correct recognition
      of intended movement was achieved in 75%-98% of trials not seen previously by the
      committee, on the basis of single EEGs of one-second duration. Frequency
      filtering did not improve recognition. Classification was optimal during the
      actual movement, but a first peak in the classification success rate was observed
      in all subjects already when they had been cued which movement later to perform.

PMID- 11235583
TI  - Strain imaging and elasticity reconstruction of arteries based on intravascular
      ultrasound video images.
AB  - Based on intravascular ultrasound (IVUS) video images, a novel motion estimation
      method combining the genetic algorithm-based optical flow method and a step-by
      step and sum strategy has been developed to estimate the displacement and strain
      distributions on the scan cross sections of the arteries. And then, real
      elasticity distributions were reconstructed under the conditions of small and
      large deformation. Experimental results of in vitro porcine arteries demonstrated
      the feasibility of the method. This investigation may have potentials to provide
      new technological means for monitoring and evaluating percutaneous transluminal
      coronary angioplasty procedure, especially, for the end users of IVUSpercimaging
      equipment.

PMID- 11235584
TI  - Noninvasive fetal electrocardiogram extraction: blind separation versus adaptive
      noise cancellation.
AB  - The problem of the fetal electrocardiogram (FECG) extraction from maternal skin
      electrode measurements can be modeled from the perspective of blind source
      separation (BSS). Since no comparison between BSS techniques and other signal
      processing methods has been made, we compare a BSS procedure based on higher
      order statistics and Widrow's multireference adaptive noise cancelling approach.
      As a best-case scenario for this latter method, optimal Wiener-Hopf solutions are
      considered. Both procedures are applied to real multichannel ECG recordings
      obtained from a pregnant woman. The experimental outcomes demonstrate the more
      robust performance of the blind technique and, in turn, verify the validity of
      the BSS model in this important biomedical application.

PMID- 11235585
TI  - Toward a better understanding of texture in vascular CT scan simulated images.
AB  - This paper shows the influence of computed tomography slice thickness on textural
      parameters by simulating realistic images issued from: 1) a 3D model of vascular
      tree, with structural and functional features and in which angiogenesis is
      related to the organ growth; 2) a projection/reconstruction process using fast
      Fourier transform. Texture analysis is performed by means of second-order
      statistics and gradient based methods.

PMID- 11235586
TI  - The case for large-size mutations.
AB  - There are no laws of physics or chemistry that forbid large mutations. Therefore,
      the "size" of a random mutation should fit the mathematics of a Poisson point
      process: The number of mutations (N), versus mutation size (MS), should obey an
      exponential relationship. Three examples are examined: A simple 15-mutation
      sequence; actual experimental data involving a sequence of 56,611 random action
      potentials (rather than mutations); and a synthetic sequence of 65,535 random
      mutations. In the latter example, with an average MS of 2.22 units, the largest
      MS is a 25-unit giant that would be associated with major changes.

PMID- 11235587
TI  - Characterization of atrial fibrillation using the surface ECG: time-dependent
      spectral properties.
AB  - Time-frequency analysis is considered for characterizing atrial fibrillation in
      the surface electrocardiogram (ECG). Variations in fundamental frequency of the
      fibrillatory waves are tracked by using different time-frequency distributions
      which are appropriate to short- and long-term variations. The cross Wigner-Ville
      distribution is found to be particularly useful for short-term analysis due to
      its ability to handle poor signal-to-noise ratios. In patients with chronic
      atrial fibrillation, substantial short-term variations exist in fibrillation
      frequency and variations up to 2.5 Hz can be observed within a few seconds.
      Although time-frequency analysis is performed independently in each lead, short
      term variations in fibrillation frequency often exhibit a similar pattern in the
      leads V1, V2 and V3. Using different techniques for short- and long-term
      analysis, it is possible to reliably detect subtle long-term changes in
      fibrillation frequency, e.g., related to an intervention, which otherwise would
      have been obscured by spontaneous variations in fibrillation frequency.

PMID- 11235588
TI  - A rate distortion optimal ECG coding algorithm.
AB  - Signal compression is an important problem encountered in many applications.
      Various techniques have been proposed over the years for addressing the problem.
      In this paper, we present a time domain algorithm based on the coding of line
      segments which are used to approximate the signal. These segments are fit in a
      way that is optimal in the rate distortion sense. Although the approach is
      applicable to any type of signal, we focus, in this paper, on the compression of
      electrocardiogram (ECG) signals. ECG signal compression has traditionally been
      tackled by heuristic approaches. However, it has been demonstrated [1] that exact
      optimization algorithms outperform these heuristic approaches by a wide margin
      with respect to reconstruction error. By formulating the compression problem as a
      graph theory problem, known optimization theory can be applied in order to yield
      optimal compression. In this paper, we present an algorithm that will guarantee
      the smallest possible distortion among all methods applying linear interpolation
      given an upper bound on the available number of bits. Using a varied signal test
      set, extensive coding experiments are presented. We compare the results from our
      coding method to traditional time domain ECG compression methods, as well as, to
      more recently developed frequency domain methods. Evaluation is based both on
      percentage root-mean-square difference (PRD) performance measure and visual
      inspection of the reconstructed signals. The results demonstrate that the exact
      optimization methods have superior performance compared to both traditional ECG
      compression methods and the frequency domain methods.

PMID- 11235589
TI  - Transactions of Biomedical Engineering (TBME).

PMID- 11235590
TI  - A theoretical analysis of acute ischemia and infarction using ECG reconstruction
      on a 2-D model of myocardium.
AB  - We developed a two-dimensional ventricular tissue model in order to probe the
      determinants of electrocardiographic (ECG) morphology during acute and chronic
      ischemia. Hyperkalemia was simulated by step changes in [K+]out, while acidosis
      was induced by reducing Na+ and Ca2+ conductances. Hypoxia was introduced by its
      effect on potassium activity. During the initial moments of ischemia, ECG changes
      were characterized by increases in QRS amplitude and ST segment shortening,
      followed in the advanced phase by ST baseline elevation, T conformation changes,
      widening of the QRS and significant decreases in QRS amplitude in spite of an
      enlarged Q. During each phase, potential proarrhythmic mechanisms were
      investigated. The presence of unexcitable regions of simulated myocardial
      infarction led to polymorphic ECG. We also observed a nonuniform deflection of
      the ST segment from beat to beat. We used similar protocols to explore the
      responses of infarcted myocardium after impairment resolving. We found that
      despite irreversible uncoupling of the necrotic region, the restored normal ionic
      concentrations produced an isopotential ST segment and monomorphic ECG complexes,
      while an enlarged Q wave was still visible. In summary, these numerical
      experiments indicate the possibility to track in the ECG pathologic changes
      following the altered electrophysiology of the ischemic heart.

PMID- 11235591
TI  - Analysis and characterization of photo-plethysmographic signal.
AB  - Qualitative assessment of the overall clinical status of the subject and
      characterization of complex cardiovascular dynamics from digital blood volume
      pulsations measured noninvasively using a photo-plethysmographic device is
      addressed. A novel concept is employed to detect the dominant nonsinusoidal
      periodicity embedded in the data series and to extract the associated periodic
      component. The detection and the extraction of periodic component is performed
      with moving window to accommodate the variations of the physiological
      oscillations. The covariance matrix formed by the gradually varying pattern is
      used as a simple measure of qualitative assessment. Further, the characterization
      of the underlying system in the light of nonlinear dynamical analysis is also
      presented. The stable subjects are shown to behave as a low-dimensional system
      whereas the diseased subjects exhibit comparatively high dimensional activity.

PMID- 11235592
TI  - Global identifiability of nonlinear models of biological systems.
AB  - A prerequisite for well-posedness of parameter estimation of biological and
      physiological systems is a priori global identifiability, a property which
      concerns uniqueness of the solution for the unknown model parameters. Assessing a
      priori global identifiability is particularly difficult for nonlinear dynamic
      models. Various approaches have been proposed in the literature but no solution
      exists in the general case. In this paper, we present a new algorithm for testing
      global identifiability of nonlinear dynamic models, based on differential
      algebra. The characteristic set associated to the dynamic equations is calculated
      in an efficient way and computer algebra techniques are used to solve the
      resulting set of nonlinear algebraic equations. The algorithm is capable of
      handling many features arising in biological system models, including zero
      initial conditions and time-varying parameters. Examples of usage of the
      algorithm for analyzing a priori global identifiability of nonlinear models of
      biological and physiological systems are presented.

PMID- 11235593
TI  - A model for the generation of synthetic intramuscular EMG signals to test
      decomposition algorithms.
AB  - As more and more intramuscular electromyogram (EMG) decomposition programs are
      being developed, there is a growing need for evaluating and comparing their
      performances. One way to achieve this goal is to generate synthetic EMG signals
      having known features. Features of interest are: the number of channels acquired
      (number of detection surfaces), the number of detected motor unit action
      potential (MUAP) trains, their time-varying firing rates, the degree of shape
      similarity among MUAPs belonging to the same motor unit (MU) or to different MUs,
      the degree of MUAP superposition, the MU activation intervals, the amount and
      type of additive noise. A model is proposed to generate one or more channels of
      intramuscular EMG starting from a library of real MUAPs represented in a 16
      dimensional space using their Associated Hermite expansion. The MUAP shapes,
      regularity of repetition rate, degree of superposition, activation intervals,
      etc. may be time variable and are described quantitatively by a number of
      parameters which define a stochastic process (the model) with known statistical
      features. The desired amount of noise may be added to the synthetic signal which
      may then be processed by the decomposition algorithm under test to evaluate its
      capability of recovering the signal features.

PMID- 11235594
TI  - Calculation of electric fields in a multiple cylindrical volume conductor induced
      by magnetic coils.
AB  - A method is presented for calculating the electric field, that is induced in a
      cylindrical volume conductor by an alternating electrical current through a
      magnetic coil of arbitrary shape and position. The volume conductor is modeled as
      a set of concentric, infinitely long, homogeneous cylinders embedded in an outer
      space that extends to infinity. An analytic expression of the primary electric
      field induced by the magnetic coil, assuming quasi-static conditions, is combined
      with the analytic solution of the induced electric scalar potential due to the
      inhomogeneities of the volume conductor at the cylindrical interfaces. The latter
      is obtained by the method of separation of variables based on expansion with
      modified Bessel functions. Numerical results are presented for the case of two
      cylinders representing a nerve bundle with perineurium. An active cable model of
      a myelinated nerve fiber is included, and the effect of the nerve fiber's
      undulation is shown.

PMID- 11235595
TI  - Optimal modeling of corneal surfaces with Zernike polynomials.
AB  - Zernike polynomials are often used as an expansion of corneal height data and for
      analysis of optical wavefronts. Accurate modeling of corneal surfaces with
      Zernike polynomials involves selecting the order of the polynomial expansion
      based on the measured data. We have compared the efficacy of various classical
      model order selection techniques that can be utilized for this purpose, and
      propose an approach based on the bootstrap. First, it is shown in simulations
      that the bootstrap method outperforms the classical model order selection
      techniques. Then, it is proved that the bootstrap technique is the most
      appropriate method in the context of fitting Zernike polynomials to corneal
      elevation data, allowing objective selection of the optimal number of Zernike
      terms. The process of optimal fitting of Zernike polynomials to corneal elevation
      data is discussed and examples are given for normal corneas and for abnormal
      corneas with significant distortion. The optimal model order varies as a function
      of the diameter of the cornea.

PMID- 11235596
TI  - A novel optical imaging method for the early detection, quantitative grading, and
      mapping of cancerous and precancerous lesions of cervix.
AB  - This paper describes a novel optical imaging method for the in vivo early
      detection, quantitative staging, and mapping of cervical cancer and precancer. A
      multispectral imaging system was developed, which is capable of performing time
      resolved imaging spectroscopy. The system was used in order to assess
      quantitatively the alterations in the light scattering properties of the cervix,
      induced selectively and reversibly in cervical neoplasias, after the application
      of acetic acid solution. Spectral imaging and analysis of cervix show that the
      maximum contrast between acetic acid responsive and nonresponsive areas is
      obtained at 525 +/- 15 nm, which is further enhanced by cutting off the regular
      component of tissue reflection, with the aid of two linear cross polarizers.
      Successive snapshot imaging at this spectral band enables the quantitative
      assessment of the temporal alterations in the intensity of the backscattered
      light, in any spatial location of the examined area. Initial clinical trials show
      that optical contrast enhancement results in a notable improvement of the
      sensitivity in detecting incipient lesions. It was also shown that the measured
      temporal characteristics of the phenomenon contain specific information, which
      enables the differentiation between neoplastic and nonneoplastic lesions, as well
      as between neoplasias of different grade. The demonstrated improved sensitivity
      and specificity highlight the potential of the method in both clinical research
      and noninvasive diagnosis.

PMID- 11235597
TI  - Post-prandial glycemic control: molecular targets for pharmacological
      intervention.

PMID- 11235598
TI  - Prandial glucose regulation--its implication in clinical practice.

PMID- 11235599
TI  - Post-prandial hyperlipidemia and hypertriglyceridemia.

PMID- 11235600
TI  - Post-prandial hyperglycemia and its implications in pregnancy and lipid
      abnormalities.

PMID- 11235601
TI  - Post-prandial hyperglycemia in pregnancy and elderly.

PMID- 11235602
TI  - Post-prandial hyperglycemia and microvascular complications.

PMID- 11235603
TI  - The post-prandial state and macrovascular disease: relevance to diabetes
      mellitus.
AB  - There is increasing evidence that the post-prandial state is an important
      contributing factor to the development of atherosclerosis. In non-diabetic
      subjects the atherosclerotic risk factors comprised in the categories of lipids,
      coagulation system and endothelial function may be adversely modified in the post
      prandial phase. The generation of an oxidative stress may be the common pathway
      through which eating may induce these alterations. In diabetic patients these
      phenomena may be amplified by post-prandial hyperglycemia. There is a growing
      thought that diabetes is a cardiovascular disease.

PMID- 11235604
TI  - Relevance of glycemic index in the management of post-prandial glycemia.

PMID- 11235605
TI  - New pharmacological development (alpha glucosidase inhibitors, amylin analogues,
      GLP-1, thiozolidinediones, short acting insulin analogues).

PMID- 11235606
TI  - Current understanding regarding the role of repaglinide in post-prandial
      hyperglycemia.

PMID- 11235607
TI  - The role of prandial glucose regulation with repaglinide in addressing the
      problem of hypoglycemia in the treatment of type 2 diabetes.

PMID- 11235608
TI  - Combination therapy in type 2 diabetes: the role of repaglinide.

PMID- 11235609
TI  - Monitoring and natural history of post-prandial hyperglycemia.

PMID- 11235611
TI  - Emergency management of poisoned patient.

PMID- 11235610
TI  - Cardiogenic shock in acute myocardial infarction.

PMID- 11235612
TI  - Acute renal failure in the tropics.

PMID- 11235613
TI  - Tension pneumothorax.

PMID- 11235614
TI  - Wide QRS tachycardia.

PMID- 11235615
TI  - Coma--basic considerations.

PMID- 11235616
TI  - Hyperglycemic emergencies in diabetes mellitus.

PMID- 11235617
TI  - Emergency treatment of tetanus.

PMID- 11235618
TI  - Immediate interventions in acute myocardial infarction.

PMID- 11235619
TI  - Septic shock.

PMID- 11235620
TI  - Cerebral malaria.

PMID- 11235621
TI  - Acute liver failure.

PMID- 11235622
TI  - Acute heat illnesses.

PMID- 11235623
TI  - Acute respiratory failure.

PMID- 11235624
TI  - Hypertensive crisis.

PMID- 11235625
TI  - Emergencies in purpuric disorders.

PMID- 11235626
TI  - Cardiac tamponade.

PMID- 11235627
TI  - Insulin biosynthesis, storage and secretion.

PMID- 11235628
TI  - Insulin kinetics.

PMID- 11235629
TI  - Patterns of insulin administration in NIDDM.

PMID- 11235630
TI  - IDDM: day to day management.

PMID- 11235631
TI  - Hyperinsulinemia: an innocent bystander?

PMID- 11235632
TI  - Insulin sensitizers.

PMID- 11235633
TI  - Insulin allergy.

PMID- 11235634
TI  - History of insulin.

PMID- 11235635
TI  - Animal insulins.

PMID- 11235636
TI  - Xenographic transplantation of monkey pancreatic islets into rats.
AB  - Islets of Langerhans were isolated from the monkey pancreatic by collagenase
      digestion method. Freshly isolated monkey pancreatic islets were transplanted
      under the renal capsule of normal rats. Treated group of rats received
      Cyclosporine A injections and the control group of rats did not receive any drug.
      In Cyclosporine A treated rats the monkey islets were not destroyed. They
      maintained their normal structural integrity with occasional neutrophils
      surrounding the islets. In the untreated rats dense infiltration of neutrophils
      destroyed the islets in three days. On the seventh day dense infiltration of
      lymphocytes was seen. Granulomas composed of epitheloid cells and occasional
      multinucleated Langerhans type giant cells were seen on the fourteenth day.

PMID- 11235637
TI  - Insulin secretagogues.

PMID- 11235639
TI  - [Vasculitis].
AB  - Systemic vasculitis is a rare condition that usually takes a chronic and often
      unpredictable course. Long-term outcome is crucially dependent on a close
      cooperation between the primary caregiver and the specialist. The tentative
      diagnosis is based on the medical history and clinical examination and verified
      by laboratory diagnostics, high-resolution imaging and histological assessment.
      The primary aim of therapy is to induce remission and provide emergency treatment
      of any vital organs that may be in jeopardy. Later on, remission maintenance and
      glucocorticoid sparing are important targets. During this phase, it is important
      to differentiate between disease activity and disease damage when optimizing the
      drug regimen. In addition to the basic treatment, arterial blood pressure should
      be controlled, screening for cardiovascular risk factors conducted and infections
      identified early. Nowadays, good outcomes can be achieved thanks to improved
      diagnostic tests, a broader therapeutic spectrum and more effective monitoring.

PMID- 11235638
TI  - [Para-infectious vasculitis].
AB  - Vasculitis is histologically characterized by inflammatory infiltrates of the
      vessels. In case of secondary vasculitis, the etiology is known. It may be an
      infection, a neoplasia, drugs or an autoimmune disease. In contrast, in primary
      vasculitis, no triggering event can be detected. In case of vasculitis associated
      to infection, the skin lesion may be the clue for the underlying infection. In
      case of endocarditis (Osler node, Janeway lesion) or sepsis due to Pseudomonas
      aeruginosa (ecthyma gangrenosum), the skin lesions are quite specific for the
      underlying disease. Other skin lesions are just an unspecific reaction to a
      microbial stimulus. Five clinical examples of vasculitis associated to infection,
      and an important non-infectious differential diagnosis are presented. The cases
      underline that a broad general work-up with multiple serological tests is neither
      cost-effective nor diagnostically rewardable. In contrast, if vasculitis is
      suspected to be caused by infection, the individual work-up should be based on
      the case-history, the epidemiology and the clinical presentation.

PMID- 11235640
TI  - [Conservative therapy in varicose symptom complex].
AB  - This article deals with the conservative management of light and severe forms of
      varicosities as well as chronic venous insufficiency along with subjective
      symptoms and trophic skin changes. Approximately 40% of the population shows
      minor forms and another 10% shows major forms of varicosities. The prevalence of
      advanced stages of chronic venous insufficiency is approximately 3%. Compression
      therapy represents the mainstay of anti-edema treatment. Elastic bandages are
      mainly used during the acute phase, and compression stockings are rather
      recommended to maintain the result. The differences of short stretch and long
      stretch bandages, as well as the classes of compression therapy are discussed.
      Physical therapy, such as joint mobilization, ambulation exercises, and lymph
      drainage may further support edema reduction in severe cases. Edema-protective
      drugs can be justified as adjuvant treatment. The pharmacology and action of
      these substances has been further elucidated by both laboratory and clinical
      studies. It has been shown that the continuous use of these substances during 8
      12 weeks can reach the anti-edematous effect of class II-stockings. Sclerotherapy
      is especially useful in the treatment of smaller caliper reticular varicosities
      and teleangiectatic veins. The development of new vascular lasers with a long
      pulse duration has added to the options in the treatment of leg teleangiectasias,
      although these expensive techniques cannot be regarded a standard therapy.
      Advanced stages of chronic venous insufficiency are also amenable to conservative
      treatment. In these cases, an exact vascular examination is highly recommended.
      Interventional treatment of relevant peripheral arterial disease and of
      superficial venous insufficiency can impressively improve the quality of life of
      these patients, even at an elderly age. Moreover, the role and differential
      indication of synthetic dressings in the local therapy of chronic leg ulcers is
      explained in-depth.

PMID- 11235641
TI  - [Minimally invasive therapy in varicose veins].
AB  - In patients with varicose vein a duplex ultrasound is absolutely necessary prior
      to surgery in order to check the deep and the superficial vein systems. A
      standard classification is recommended to describe the type of venous
      insufficiency. Teleangiectasis and small varicose veins can be treated by
      sclerotherapy, but laser-therapy gets more and more popular. The inverting
      (partial)stripping of the greater and/or lesser saphenous vein avoiding nerve
      damage has gained popularity as did the miniphlebectomy. Newer methods using heat
      by radiofrequency order cryosurgery should generate less complications and have
      to show similar long term results than the classical procedures. Subfascial
      endoscopic perforator vein surgery (SEPS) is effective. Local or extended
      fascioctomy followed by skin transplantation in patients with recurrent
      ulcerations is considered as an option of therapy.

PMID- 11235642
TI  - [Therapy of venous thromboembolism].
AB  - Deep venous thrombosis and lung embolism are often considered as two different
      variants of the same disease. This is evident not only in the same pathogenesis
      but also in a comparable prognosis and therapy. Therefore the term "venous
      thromboembolism" is used in recent literature. The main therapy of venous
      thromboembolism is anticoagulation and initially consists of (low molecular
      weight) heparin followed by a regimen with oral anticoagulants--the duration
      depending on the indication. Pharmacokinetic advantages of low molecular weight
      heparin (LMWH) allow weight-adapted dosing with daily subcutaneous injections in
      most patients. LMWH do not require any laboratory controls. Therefore outpatient
      treatment should be possible for about 75% of patients with venous
      thromboembolism. Outpatient treatment of lung embolism, however, is still being
      studied and therefore not recommended apart from clinical trials. In cases of
      massive venous thromboembolism additional treatment with thrombolytic agents or
      surgery is needed. Adequately fit compression stockings can reduce the risk of
      post-thrombotic syndrome after deep venous thrombosis. Patients on long-term oral
      anticoagulation may learn to measure their INR with a portable coagulation
      monitor and adjust the dosage of the anticoagulants themselves--this method is
      called patient self-management of oral anticoagulation.

PMID- 11235643
TI  - [The ideal assisted ventilation: a never ending story?].

PMID- 11235644
TI  - Relevant key-points from the history of anaesthesia at the eve of the third
      millenium.

PMID- 11235646
TI  - [Traditional artificial ventilation. General principles].
AB  - Mechanical ventilation is generally applied on patients affected by acute
      respiratory failure (ARF) on the basis of hemogasanalysis, hemodynamics and X-ray
      features. The modification of ventilatory pattern is based on problem the
      modification of data concerning mechanical variation. In this study the most
      important mechanical measures and their consequences on ventilatory strategy are
      discussed.

PMID- 11235645
TI  - [Biochemical and metabolic aspects of oxyradical pathology in the hypoxic
      ischemic reperfused human skeletal muscle tissue. Clinical markers and
      therapeutic approach].
AB  - BACKGROUND: Following our previous studies on the biomolecular and biochemical
      aspects of the human tissue oxidative damage due to hypoxia, ischemia and
      reperfusion, aim of the present work is to evaluate the role played by oxyradical
      generation in the morphofunctional cellular injury. We evaluated the tissue
      levels of some metabolic markers (MDA, Catalase, Uric Acid) to obtain a
      pathogenic picture and then a therapeutic approach closely related to the
      cellular biodynamics. METHODS: A skeletal muscle samples were taken during
      elective knee orthopedic surgery in 20 consecutive patients. The biopsies were
      taken in normoxic conditions and after 5 +/- 1 and 62 +/- 3 min form tourniquet
      application and finally 21 +/- 2 min following muscle reperfusion. The samples
      were assayed for tissue Malondialdeyade (MDA), uric acid and catalase (CAT)
      contents with HPLC and fluorimetric procedures. All data were evaluated in terms
      of computerized statistical analysis. RESULTS: When compared to normoxic tissue
      (1.24 +/- 0.26 nmoli.mg-1 protein), the MDA levels show a moderate increase in
      hypoxic (1.66 +/- 0.12) and ischemic tissue (1.78 +/- 0.13), while highly
      significant is the rise in reperfused muscle MDA content (5.94 +/- 0.15). The
      uric acid as far as CAT shows no appreciable alterations in hypoxia and ischemia.
      Following reoxygenation an increase in uric acid contents with a concomitant CAT
      tissue consumption appear evident. CONCLUSIONS: The obtained data seem to
      underline the cytoprotective role played by adaptive changes in the hypoxic and
      ischemic human cells. On the contrary, the rapid reoxygenation of the ischemic
      tissue appears to start oxyradical neo-generation. In clinical and therapeutic
      terms these observations underline a peculiar and different approach to the
      critically ill patient.

PMID- 11235647
TI  - [Non-invasive ventilation in intensive care. Update 2000].
AB  - NIV indications and application in critically ill patients have considerably
      expanded in the last few years: the aim of this paper is to shortly review NIV
      main indications, on the basis of data from the current scientific literature.

PMID- 11235648
TI  - [Mechanical ventilation in acute respiratory distress syndrome. New Trends].
AB  - Adult Respiratory Distress Syndrome (ARDS) is characterized by an inflammatory
      process affecting endothelial and epithelial lung tissue, with occurrence of
      hypoxemia, bilateral X-ray infiltrates, in absence of cardiogenic edema. The
      introduction of Computerized Tomography brought some improvements in
      understanding the ARDS lung, leading to a pulmonary model made up of three zones:
      1) normally inflated, 2) recruitable and 3) consolidated. It has now been well
      established that mechanical ventilation of ARDS lung presents some iatrogenic
      effects that may affect mortality. Several mechanisms are considered responsible
      of ventilator-associated lung injury (VALI): high inspired oxygen fraction, high
      inspiratory plateau pressure and large tidal volume, and intratidal collapse and
      reinflation of alveolar units. In these years, different ventilatory strategies
      in the treatment of ARDS patients have been suggested to decrease and to prevent
      VALI. The most important one seems to be the application of an appropriate value
      of tidal volume and positive end-expiratory pressure (PEEP). Several randomized
      studies, which compared low versus high tidal volumes, have recently been
      finished. Despite some differences, it seems that a ventilatory management
      limiting inspiratory plateau pressure to 35 cmH2O or lower may be useful to
      reduce VALI and mortality, also in association with a PEEP level sufficient to
      decrease the end-expiratory collapse. Another useful ventilatory tool for
      improving gas exchange and decreasing VALI in ARDS patients is likely the prone
      positioning, even if further studies are necessary to understand how this
      maneuver may really affect mortality. Another therapeutic instrument for
      improving oxygenation in ARDS patients is the inhalation of NO. Unfortunately,
      this pharmacological agent does not seem to affect the outcome of these patients.

PMID- 11235649
TI  - [Mechanical ventilation in the emergency room].
AB  - The respiratory failure in polytrauma patients and respiratory failure of
      different origin (COPD, pneumonia, pulmonary edema). In the first case invasive
      ventilation seems to be preferable and so the tracheal intubation, in emergency,
      with its more important guidelines. In the second case there are important
      physiopathological elements to consider NIMV the best first approach for
      ventilatory support.

PMID- 11235650
TI  - [Respiratory emergencies in the extra-hospital environment].
AB  - Prehospital care is a fundamental element for the patient's outcome, in the field
      of medical and surgical emergencies. There are different strategies about it,
      defined "scoop and run" and "stay and play". The choice among the different
      strategies, in our opinion, must be well-suited to the underlying pathophysiology
      of the illness. The best approach to the care of Acute Respiratory Failure is
      chosen on the ground of the possible and rapid reversibility of the pathology.
      Nowadays, classical semeiology is integrated by portable devices that allow the
      real time monitoring of pulse oximetry, electrocardiography, arterial pressure
      and heart rate, capnometry, blood gas analysis, serum electrolites, etc.
      Maintenance of airway patency can be achieved by many devices, according to the
      patient's neurological conditions. In common opinion the early respiratory
      support reduces patient's stay in hospital and his outcome.

PMID- 11235651
TI  - [Home mechanical ventilation: the extra-hospital phase].
AB  - Home mechanical ventilation is the choice option, when there are no
      contraindications of medical or socio-economic order, in all cases of impossible
      complete weaning from ventilatory support. Easy to use, reliable and size limited
      positive pressure ventilators lead to a spread diffusion of this technique. In
      the patient/ventilator interface, tracheostomy is the golden choice for patient
      with great reduction in spontaneous ventilatory ability. For all other patients,
      perfectioning of non-invasive access (nasal and oral nasal mask) represent an
      effective progress. Major limitations in home ventilation are still, up to
      present, the lack of multidisciplinary structures able to give territorial
      assistance. Home ventilation therapy in the experience of the Policlinico
      Universtitario "La Sapienza", Rome is presented.

PMID- 11235652
TI  - [Neuronal plasticity and neuropathic pain].
AB  - The authors have analysis the physiopathology of neuropathic pain, focusing in
      particular on the plastic phenomena at the level of the central nervous system.
      Plastic phenomena take the form of anatomic and neurochemical alterations. In
      relation to the former, excitatory amino acids play a fundamental role, causing a
      state of hypersensitivity of N-menthyl-D aspartate (NMDA) receptors (excitation
      toxicity) which in turn cause the degeneration of inhibitory interneurons
      localised in the I-III laminae of the dorsal cornu. This hyperactivation is
      responsible for the presence of a discharge input that lasts for minutes after a
      nociceptive stimulus, a phenomenon known as long-term potentiation (LTP) on long
      term depression (LTD). The authors also analysed the role of other
      neurotransmitters and their possible interactions. Neurochemical alterations are
      coupled with anatomic modifications, like sprouting, at the level of the dorsal
      cornu laminae and dorsal root ganglia. These neuroplastic phenomena lead to an
      alteration in the central mechanisms of pain, for A-fibre mediated mechano
      allodynia, a clinical phenomenon that differs from thermal hyperalgesia in both
      physiopathology and clinical prognosis. The role played by the sympathetic system
      in neuropathic pain is also discussed. The authors also raise a number of
      clinical considerations regarding the different nature of spontaneous pain,
      allodynia and hyperalgesia. New physiopathological knowledge is a useful tool for
      pharmacological and clinical research, as well as for treatment of syndromes
      secondary to neuropathic pain.

PMID- 11235653
TI  - [Clinical-organizational recommendations for anesthesia in day surgery of the
      SIAARTI/AAROI Commission on Day Surgery].

PMID- 11235654
TI  - New rules set national uniform standard for protecting privacy of medical
      records.

PMID- 11235655
TI  - 2001 federal budget increases SAMHSA funds for mental illness and substance abuse
      programs.

PMID- 11235656
TI  - Measurement of scapular asymetry and assessment of shoulder dysfunction using the
      Lateral Scapular Slide Test: a reliability and validity study.
AB  - BACKGROUND AND PURPOSE: The Lateral Scapular Slide Test (LSST) is used to
      determine scapular position with the arm abducted 0, 45, and 90 degrees in the
      coronal plane. Assessment of scapular position is based on the derived difference
      measurement of bilateral scapular distances. The purpose of this study was to
      assess the reliability of measurements obtained using the LSST and whether they
      could be used to identify people with and without shoulder impairments. Subjects.
      Forty-six subjects ranging in age from 18 to 65 years (X=30.0, SD=11.1)
      participated in this study. One group consisted of 20 subjects being treated for
      shoulder impairments, and one group consisted of 26 subjects without shoulder
      impairments. METHODS: Two measurements in each test position were obtained
      bilaterally. From the bilateral measurements, we derived the difference
      measurement. Intraclass correlation coefficients (ICC [1,1]) and the standard
      error of measurement (SEM) were calculated for intrarater and interrater
      reliability of the difference in side-to-side measures of scapular distance.
      Sensitivity and specificity of the LSST for classifying subjects with and without
      shoulder impairments were also determined. RESULTS: The ICCs for intrarater
      reliability were .75, .77, and .80 and .52, .66, and .62, respectively, for
      subjects without and with shoulder impairments in 0, 45, and 90 degrees of
      abduction. The ICCs for interrater reliability were .67, .43, and .74 and .79,
      .45, and .57, respectively, for subjects without and with shoulder impairments in
      0,45 and 90 degrees of abduction. The SEMs ranged from 0.57 to 0.86 cm for
      intrarater reliability and from 0.79 to 1.20 cm for interrater reliability. Using
      the criterion of greater than 1.0 cm difference, sensitivity and specificity were
      35% and 48%, 41% and 54%, and 43% and 56%, respectively, for 0, 45, and 90
      degrees of abduction. Sensitivity and specificity based on the criterion of
      greater than 1.5 cm difference were 28% and 53%, 50% and 58%, and 34% and 52%,
      respectively, for the 3 scapular positions. CONCLUSION AND DISCUSSION: Our
      results suggest that measurements of scapular positioning based on the difference
      in side-to-side scapular distance measures are not reliable. Furthermore, the
      results suggest that sensitivity and specificity of the LSST measurements are
      poor and that the LSST should not be used to identify people with and without
      shoulder dysfunction.

PMID- 11235657
TI  - [Modern history of psychiatry in Japan].

PMID- 11235658
TI  - [Japanese Society of Neuropsychiatry for Epilepsy].

PMID- 11235659
TI  - [History and future prospect of Japanese Society of Clinical Neurophysiology].

PMID- 11235660
TI  - [Life of aged patients with dementia viewed from the experience of patient day
      dare].

PMID- 11235661
TI  - Quality pays.

PMID- 11235662
TI  - Seizures, lateral decubitus, aspiration, and shoulder dislocation: Time to change
      the guidelines?
AB  - The recommendation to position a patient having a seizure on a lateral decubitus
      is aimed at minimizing the risk of aspiration. The authors reviewed the database
      of the Epilepsy Foundation Clinic of South Florida for patients with epilepsy
      treated for pneumonia between May 1999 and May 2000 and patients admitted to two
      university telemetry units who had dislocation of the shoulder during an
      epileptic seizure. Over 2 months, 2 of 733 adults with intractable seizures had
      aspiration pneumonia after a generalized tonic clonic seizure (GTCS). Although no
      study has specifically addressed the problem of aspiration pneumonia in adults
      with GTCS, our findings suggest this problem is not common. From the two epilepsy
      centers, 5 of 806 patients dislocated a shoulder during a seizure. Video
      recordings showed that these patients were positioned in a lateral decubitus by
      staff while still having the convulsion. The dislocated shoulder in all cases was
      on the lower side. The risk of shoulder dislocation in a convulsing patient
      positioned in a lateral decubitus is less than 1%. Nevertheless, dislocations can
      result in disabling recurrences and are easily preventable. Because aspiration is
      more likely in the postictal rather than ictal phase of a GTCS, when oral
      secretions are not usually increased and there is cessation of respiratory
      movements, lateral decubitus should only be implemented after cessation of the
      convulsion, In inpatients (such as those on telemetry), secretions may be better
      managed by bedside aspiration of the oral cavity.

PMID- 11235663
TI  - Universal health coverage.  Five good reasons why nurses should champion it.

PMID- 11235664
TI  - [Regulation of blood sugar level].

PMID- 11235665
TI  - Bibliography of Ulrich Wolf.

PMID- 11235666
TI  - How can we introduce new technology safely and effectively?

PMID- 11235667
TI  - Short-term (30-day) outcome of endovascular treatment of abdominal aortic
      aneurism: results from the prospective Registry of Endovascular Treatment of
      Abdominal Aortic Aneurism (RETA).
AB  - OBJECTIVES: to assess the early morbidity and mortality of a new treatment, the
      endovascular repair of abdominal aortic aneurysms, during its introduction into
      clinical practice. DESIGN: a prospective voluntary registry collecting
      demographic and risk factor data, details of aneurysm morphology, procedure
      performed, immediate and 30-day outcomes. SETTING: thirty-one U.K. centres
      performing endovascular repair submitted data. RESULTS: six hundred and eleven
      cases were registered in three years of data collection (January 1996 to December
      1998). Four per cent of patients received an aortic tube device, 60% an aorto-bi
      iliac device and 36% an aorto-uni-iliac device and a crossover graft (AUIC).
      Conversion to open repair was required in 5% of cases, with more conversions in
      the AUIC group (OR 2.9 (95% CI: 1.3-6.4)p=0.01). Post procedure complications
      occurred in 25% of cases. Unfit patients had significantly more complications
      than fit patients (35% vs 20% for fit patients (OR 1.8 (95% CI: 1.2
      2.7)p=0.007)). At 30 days aneurysms were excluded in 90% of cases. Endoleaks were
      more common in larger aneurysms (2% if aneurysms were <6 cm in diameter vs 10% if
      >6 cm, OR 5.6 (95% CI: 2.1-14.9)p=0.0006). The overall mortality was 7% but was
      significantly higher for AUIC devices, (4% for combined aortic tube and bi-iliac
      devices (AT/BI) vs 12%, OR 2.6 (95% CI: 1.2-5.9 p=0.018)), and unfit patients (4%
      for fit patients vs 18%, OR 4.3 (95% CI: 2.0-9.5)p<0.001). CONCLUSIONS:
      endovascular repair is feasible with short-term outcomes comparable to those of
      conventional surgical repair. In unfit patients the possible benefit in life
      expectancy gain must be balanced against the morbidity and mortality of the
      procedure.

PMID- 11235668
TI  - [Induction of apoptosis of splenic lymphocytes in mice by accelerated carbon
      ions].
AB  - To assess the capacity of heavy ions to induce apoptosis in lymphocytes, mice
      have been irradiated with accelerated carbon ions (95 MeV/nucleon) at doses
      ranging from 0.1 to 4 Gy. Their spleens were removed 24 h later and gently
      dissociated to prepare a single cell suspension. Mononuclear cells were then
      maintained in culture at 37 degrees C, and the occurrence of apoptosis in these
      cells was analysed 24 h later. Lymphocytes were also irradiated in vitro, in the
      presence of Ac-DEVD-CHO, a potent caspase-3 and -7 inhibitor. Results from three
      experiments performed at the Grand Accelerateur National d'Ions Lourds (GANIL,
      Caen, France) are reported here. They indicate that carbon ions induce a marked,
      dose-dependent, reduction of the spleen weight and cellularity. However, in sharp
      contrast with spleen cells prepared from X-ray irradiated mice, only a slight
      increase of apoptosis is evidenced in cultured lymphocytes from mice irradiated
      with heavy ions. The significance of such results is discussed. So far, few data
      exist concerning the biological effects of heavy ions, in particular their
      capacity to induce apoptosis in lymphocytes; the present study provides useful
      clues for further investigations.

PMID- 11235669
TI  - [Electronic coupling and charge transfer of DNA: energy control].
AB  - The influence of the energetic gap on the effective distance-decay rate of
      electronic coupling (beta(eff)) in DNA is investigated in the context of the
      superexchange mechanism. The DNA double helix is described by a tight-binding
      electronic Hamiltonian model, in which all orbitals have the same energy and
      interact with one another through an exponentially decaying function of distance.
      Our numerical results concerning the beta(eff) values obtained for two different
      DNA molecules are analyzed within the theoretical framework of the "continuous
      medium approximation," previously developed by Lopez-Castillo et al. (J.-M. Lopez
      Castillo, A. Filali-Mouhim, I.L. Plante, and J.-P. Jay-Gerin. J. Phys. Chem. 99 :
      6864-6875, 1995). We find that the intervening DNA bridge between the donor and
      acceptor sites is defined by a unique dimensionless control parameter gamma/E,
      where E is the energy of the orbitals of this medium with respect to those of the
      redox site orbitals (energetic gap) and gamma is the electronic band width of the
      bridge considered as a continuous medium. In the narrow-band regime, our "through
      space" coupling model predicts beta(eff) values that are in good order of
      magnitude agreement with those calculated by other theoretical approaches as well
      as with those obtained from experiment. Moreover, under equivalent energetic
      conditions, the DNA-mediated transfers of holes and electrons differ
      considerably. This difference depends upon the sign of the parameter gamma/E.

PMID- 11235670
TI  - [Dosimetry with radiosensitive gels in radiotherapy. Methods].
AB  - The goal of conformal radiotherapy is to concentrate the dose in a well-defined
      volume by avoiding the neighbouring healthy structures. This technique requires
      powerful treatment planning software and a rigorous control of estimated
      dosimetry. The usual dosimetric tools are not adapted to visualize and validate
      complex 3D treatment. Dosimetry by radiosensitive gel permits visualization and
      measurement of the three-dimensional dose distribution. The objective of this
      work is to report on current work in this field and, based on our results and our
      experience, to draw prospects for an optimal use of this technique. Further
      developments will relate to the realization of new radiosensitive gels
      satisfying, as well as possible, cost requirements, easy realization and use,
      magnetic resonance imagery (MRI) sensitivity, tissue equivalence, and stability.
      Other developments focus on scanning methods, especially in MRI to measure T1 and
      T2.

PMID- 11235671
TI  - [Radiation induced lipid peroxidation: factors which determine the oxidizability
      of lipids].
AB  - Lipids are the essential components of cell membranes and lipoproteins. Their
      peroxidation plays an important role in numerous pathologies in which oxidative
      stress is involved. Lipid peroxidation occurs through a chain reaction that
      contributes to membrane damage in cells. It results in the conversion of fatty
      acids to polar hydroperoxides and leads to the breakdown or malfunction of the
      membrane. Lipids are amphiphilic molecules that aggregate in aqueous solutions
      into micelles and liposomes. The effect of this structural organization is
      significant in studies of radiation-induced peroxidation damage in highly ordered
      biological systems such as biological membranes. In this paper, a synthesis of
      the data concerning radioinduced lipid peroxidation is completed by an original
      review of the different parameters that determine lipid oxidizability. In
      addition, the influence of lipid aggregation and the effect of molecular packing
      are discussed.

PMID- 11235672
TI  - [Detection of hydroxyl and superoxide radicals in radiolysis of water with time
      resolved chemiluminescence].
AB  - A new method for the detection of low concentrations of hydroxyl and superoxide
      radicals, formed by water radiolysis, is described in this article. The method
      used is the time resolved chemiluminescence. It has been performed with an
      electron beam delivered by a Febetron 707 accelerator. This method allows to
      measure hydroxyl and superoxide radical concentrations in a large range of
      concentrations, between 10(-5) and 10(-8) M.

PMID- 11235673
TI  - [Production of superoxide radicals with pulse radiolysis of water with high
      linear energy transfer].
AB  - The radiolysis of water with heavy ions of high linear energy transfer (LET) (
      dE/dx) is characterized, in deaerated medium, by the production of superoxide
      anions, the radiolytic yields of which increase with the LET. Radiobiological
      interest in such radical species comes from the oxidative stress which may be
      generated by their dismutation in O2 and H2O2 in anoxic medium (radiotherapy with
      heavy ions). A brief review of the measurements of superoxide free radicals in
      aqueous solution by indirect or direct methods is presented. Moreover, some
      experimental results obtained by pulse radiolysis with Ar18+ ions (TEL = 290 keV
      x microm(-1)), are described. The interpretation of the kinetics takes into
      account the superoxide absorbance and that of hydrogen peroxide, which is present
      at the millisecond time scale.

PMID- 11235674
TI  - [Radiolytic oxidation of tamoxifen with the free radicals OH- and/or HO2-].
AB  - Tamoxifen is the most widely used antiestrogen in the treatment of breast cancer.
      In this work, we have studied its antioxidant properties. We have investigated
      the ability of tamoxifen to scavenge, in vitro, *OH and (or) HO2* free radicals
      that are produced by water radiolysis. Aqueous solutions of tamoxifen of
      concentrations ranging between 10(-5) and 2.5 x 10(-5) M have been irradiated
      (gamma 137Cs) in aerated acidic medium (H3PO4 10(-3) M or HCOOH 10(-1) M). The
      results show that tamoxifen reacts quantitatively with *OH free radicals but does
      not react with HO2* free radicals under our experimental conditions.

PMID- 11235675
TI  - [Intervention by nitric oxide, NO, and its oxide derivatives particularly in
      mammals].
AB  - Nitric oxide (NO) is a natural and stable free radical produced in soil and water
      by the bacteriological reduction of nitrites and nitrates and in animals by the
      enzyme oxidation of L-arginine. NO is biosynthesised by finely regulated
      enzymatic systems called NO-synthases and readily diffuses through tissues. It
      reacts rapidly with hemoproteins and iron-sulphur centers to form nitrosylated
      compounds. It oxidises more slowly to form nitrogen oxides that nitrosate thiols
      into thionitrite. NO is transported in these various forms and released
      spontaneously or through yet unclear mechanisms into most cells; it also
      regulates oxygen consumption at the mitochondrial respiratory chain level through
      interaction with cytochrome oxidase. In the cardiovascular system, NO lowers
      blood pressure by activating a hemoprotein, the guanylate cyclase present in
      muscle cells; through such interaction it acts also as a neuromediator and
      neuromodulator in the nervous system. However, many of NO's roles result from
      rapid coupling to other radicals; for example, it reacts with the superoxide
      anion (O2-) to form oxoperoxinitrate (ONOO-, also known as peroxynitrite). This
      strong oxidant of metallic centers, thiols, and antioxidants is also able to
      convert tyrosine to 3-nitrotyrosine and to act upon tyrosine residues contained
      in proteins. The biological aspects of the roles of NO are presented with
      particular respect to the rapid interactions of NO with hemoproteins' iron and
      other radicals. Concurrently, NO oxidation enables nitrosation reactions
      primarily of thiols but ultimately of nucleic bases. The thionitrite function (R
      S-NO) thus formed and the dimerisation and nitration of tyrosine residues are
      protein post-translational modifications that are being investigated in animals.

PMID- 11235676
TI  - Polymers and surfactants on the basis of renewable resources.
AB  - A new strategy for the preparation of different polymers and special surfactants
      was developed. First, unsaturated fatty acid methyl esters obtained from plant
      oils were converted to terminally unsaturated esters and alpha-olefins by
      metathesis with ethylene using heterogeneous rhenium or homogeneous ruthenium
      catalysts. These esters were directly copolymerized with ethylene by an insertion
      type palladium-catalyzed polymerization to functionalized polyolefins. Polyesters
      were synthesized by metathetical dimerization of omega-unsaturated esters and
      subsequent polycondensation of the produced internally unsaturated dicarboxylic
      esters or by acidic transesterification with petrochemical diols and additional
      acyclic diene metathesis polymerization. Omega-epoxy fatty acid methyl esters,
      achieved by a new method of chemo-enzymatic epoxidation, were converted into
      polyethers with comb-structure catalyzed by aluminoxanes on the one hand and into
      sugar surfactants by nucleophilic ring-opening with amino carbohydrates on the
      other hand.

PMID- 11235677
TI  - The challenges of health disparity and cardiovascular outcomes.

PMID- 11235678
TI  - Progress in international cardiac surgery: emerging strategies.

PMID- 11235679
TI  - Use of omentum for mediastinal tracheostomy after total laryngoesophagectomy.
AB  - BACKGROUND: Carcinomas of the cervicothoracic esophagus frequently invade the
      trachea and complete removal of the tumor often requires mediastinal
      tracheostomy. Traditionally, this surgical management was associated with high
      morbidity and mortality. Several types of myoctaneous flaps have been used for
      mediastinal tracheostomy to reduce the complication. We present our experience
      with a new technique for construction of mediastinal tracheotomy after total
      laryngoesophagectomy and reconstruction with the stomach. METHODS: The anterior
      chest wall was amply resected and the distal end of the trachea was placed low
      between the superior vena cava and aortic arch. We mobilized the entire omentum
      with the stomach and brought them up to the neck through the posterior
      mediastinum. The omentum was put around the trachea, main arteries, and the
      anastomosis. RESULTS: Seven mediastinal tracheostomies were performed using this
      method. There was no hospital death. Complications included respiratory failure
      (2 patients) and pyothorax (1 patient). Anastomotic leakage and inominate artery
      rupture were not experienced. Postoperative survival was disease dependent. All
      patients were discharged with satisfactory oral food intake, good airway
      condition, and excellent cosmetic appearance. CONCLUSIONS: We suggest the use of
      the omentum as a simple and reliable technique in constructing mediastinal
      tracheostomy following total laryngoesophagectomy for cervicothoracic esophageal
      cancer.

PMID- 11235680
TI  - Esophageal resection in elderly esophageal carcinoma patients: improvement in
      postoperative complications.
AB  - BACKGROUND: Advanced age is considered to be a relative contraindication for
      radical esophagectomy with a three-field lymph node dissection. METHODS:
      Preoperative risks, postoperative morbidity and mortality, and long-term survival
      in 55 elderly patients (> or =70 years) who had undergone extensive esophagectomy
      for esophageal carcinoma were compared with those of 149 younger patients (<70
      years). RESULTS: Elderly patients had worse preoperative cardiopulmonary function
      and had more frequent postoperative cardiopulmonary complications compared with
      younger patients (p < 0.05). The postoperative death rate was not statistically
      different between the elderly (10.9%) and younger groups (5.4%). When the study
      period was divided into an early and a late phase, the postoperative death rate
      dropped significantly (p < 0.05) in recent years (1.4%) when compared with the
      previous era (10.0%). The overall survival rates were not different between
      elderly and younger patients. CONCLUSIONS: Preoperative cardiopulmonary risk
      factors and postoperative complications after esophagectomy were more frequently
      noticed in elderly patients than in younger patients. A dramatic improvement in
      postoperative death was noticed in recent years. The long-term survival of
      elderly patients after extended esophagectomy was almost similar to that in
      younger patients.

PMID- 11235681
TI  - Experience and technique of stapled mechanical cervical esophagogastric
      anastomosis.
AB  - BACKGROUND: Anastomotic leak from cervical esophagogastric anastomoses is a
      serious problem after esophagectomy. We explored the efficacy of partial or total
      mechanical anastomoses accomplished with the endoscopic linear cutting and
      stapling device as an alternative to hand-sewn anastomotic techniques. METHODS:
      During a 42-month period, 93 patients undergoing either transhiatal esophagectomy
      or a three-incisional approach to esophagectomy underwent either hand-sewn (n =
      43), partial mechanical (n = 16), or totally mechanical (n = 34) cervical
      esophagogastric anastomoses. The occurrence of postoperative anastomotic leak and
      the development of postoperative anastomotic stricturing requiring dilation
      therapy were analyzed between these groups using chi2. RESULTS: All patients
      survived esophagectomy and were available for postoperative follow-up.
      Anastomotic leak developed in 10 patients (23%) with hand-sewn, 1 patient (6%)
      with partial mechanical, and 1 patient (3%) with total mechanical anastomoses (p
      < 0.05). Anastomotic stricture development paralleled the occurrence of
      anastomotic leak rate with 25 patients (58%) with hand-sewn, 3 patients (19%)
      with partial mechanical, and 6 patients (18%) with total mechanical anastomoses
      experiencing strictures requiring dilation therapy (p < 0.05). CONCLUSIONS: These
      results suggest that partial or mechanical cervical esophagogastric anastomoses
      created with the endoscopic stapling device may be superior to hand-sewn
      anastomotic techniques.

PMID- 11235682
TI  - Investigating extrathoracic metastatic disease in patients with apparently
      operable lung cancer. The Canadian Lung Oncology Group.
AB  - BACKGROUND: The optimal approach to the investigation of possible distant
      metastases in patients with apparently operable non-small cell lung cancer who do
      not have symptoms suggesting metastatic disease is controversial. METHODS: We
      conducted a randomized, controlled trial in thoracic surgery services at mainly
      academic tertiary- and secondary-care general hospitals. We recruited 634
      patients with apparently operable, suspected or proven non-small cell carcinoma
      of the lung without findings on history, physical examination, laboratory
      testing, or imaging suggesting extrathoracic metastases. Patients were randomly
      allocated to receive either mediastinoscopy and computed tomography of the chest
      and then, depending on the results, immediate thoracotomy or bone scintigraphy
      and computed tomographic scanning of the head, liver, and adrenal glands.
      RESULTS: The relative risk of thoracotomy without cure (the combination of open
      and closed thoracotomy, incomplete resection, and thoracotomy with subsequent
      recurrence) in the full investigation group versus the limited investigation
      group was 0.80 (95% confidence interval [CI], 0.56 to 1.13; p = 0.20). Forty
      three patients in the full investigation group and 61 patients in the limited
      investigation group underwent a thoracotomy but subsequently had recurrence
      (relative risk, 0.70; 95% CI, 0.47 to 1.03; p = 0.07). Patients in the full
      investigation group were more likely to have avoided thoracotomy because of
      extrathoracic metastatic disease than those in the limited investigation group
      (22 patients versus 10 patients, respectively; relative risk, 2.19; 95% CI, 1.04
      to 4.59; p value = 0.04). The total number of negative invasive tests was six in
      the full investigation group and one in the limited investigation group (relative
      risk, 6.1; 95% CI, 0.72 to 51.0; p = 0.10) and the total number of invasive
      tests, 11 versus six, respectively (relative risk, 1.84; 95% CI, 0.68 to 4.98; p
      = 0.23). The full investigation strategy cost $823 less per patient (95% CIs
      2,482 to -725). CONCLUSIONS: Full investigation for metastatic disease in
      patients with non-small cell lung cancer without symptoms or signs of metastatic
      disease may reduce the number of thoracotomies without cure. The higher the
      threshold for considering symptoms to suggest metastatic disease, the more likely
      it is that investigation will spare patients futile thoracotomy.

PMID- 11235683
TI  - Complications associated with pulmonary resection in lung cancer patients on
      dialysis.
AB  - BACKGROUND: There are few studies available investigating the perioperative
      problems experienced by lung cancer patients on dialysis undergoing pulmonary
      resection. METHODS: A retrospective review of 7 patients on dialysis undergoing
      pulmonary resection for lung cancer was performed. RESULTS: The patient
      population consisted of 7 men, with a mean age of 59.9 years. The underlying
      kidney disease was glomerulonephritis in 5 patients and nephrosclerosis in 2. The
      mean levels of blood urea nitrogen and serum creatinine were 70.7 mg/dL and 9.4
      mg/dL, respectively. Histologic diagnoses were adenocarcinoma in 2 patients and
      squamous cell carcinoma in 5. Standard lobectomy with lymph node dissection was
      performed in all cases. There was one operation related death due to pulmonary
      edema and subsequent development of pneumonia. There were two cases of sputum
      retention and four of hyperkalemia. One patient died of cerebral bleeding that
      occurred during dialysis 2 months postoperatively. CONCLUSIONS: In patients on
      dialysis who undergo pulmonary resection, there is a high incidence of pulmonary
      complications, in addition to hyperkalemia, hemodynamic instability, and a
      tendency for postoperative dialysis-associated bleeding.

PMID- 11235685
TI  - Surgical treatment of active and sequelar forms of pulmonary tuberculosis.
AB  - BACKGROUND: The incidence of tuberculosis has risen since 1990, and in some
      countries, the resistant forms are becoming more and more frequent. Surgical
      treatment is once again needed to manage these problems. The purpose of this
      study was to analyze the indications and results of resection, which we performed
      for pulmonary tuberculosis. METHODS: From 1980 to 1997, 477 patients were
      operated on for thoracic or intrathoracic tuberculosis in Laennec Hospital, Paris
      (259 suffered lung diseases). There were 165 women and 94 men, aged 25 to 86
      years (mean 46 years), from Europe (n = 148), North Africa (n = 65), Subsaharian
      Africa (n = 34), Asia (n = 7), and the West Indies (n = 5). This population was
      reviewed concerning the lung tuberculosis (sequelae or active lesions), the
      indications of lung resection, the type of resections performed, and the results
      at 1, 6, and 12 months. RESULTS: Active lesions were present in 97 cases and
      sequelae in 162. Surgery was performed for a therapeutic purpose in 104 patients
      with sequelae, and in 10 patients with active tuberculosis (pneumonectomy, n =
      19; pleuropneumonectomy, n = 19; lobectomy, n = 54; and segmentectomy, n = 22).
      Surgery was performed for a diagnostic purpose in 54 patients with sequelae, and
      in 87 patients with active lesions (lobectomy, n = 32; segmentectomy, n = 19;
      wedge resection, n = 94, of which 11 performed by video-assisted thoracoscopy
      since 1991). One patient died after pleuropneumonectomy. We observed 25
      complications: empyema, n = 7; hemothorax, n = 2; prolonged air leaks, n = 14;
      and pneumopathy, n = 2. All patients with active lesions subsequently were given
      antitubercular drugs. Follow-up was 100% at 1 month, 57% (n = 92) and 77% (n =
      75) at 6 months for patients with sequelae and for patients with active lesions,
      respectively. All were asymptomatic with a normal chest roentgenogram. The number
      of operations for active lesions is increasing over the years, while it is
      decreasing for sequelar lesions. CONCLUSIONS: In our department, surgery is being
      performed more frequently to make a diagnosis in cases of active tuberculosis,
      and to treat complicated lesions in case of sequelae. Lung resection for active
      tuberculosis evolving under treatment or for drug resistance was rare. However,
      our study confirms the good results commonly obtained by surgery and supports the
      idea that surgery may help eradicate tuberculosis when social and economic
      circumstances render its medical management difficult or hazardous.

PMID- 11235684
TI  - Fluoroscopy-assisted thoracoscopic surgery after computed tomography-guided
      bronchoscopic barium marking.
AB  - BACKGROUND: Small lesions of the peripheral lung have been detected more
      frequently with the recent prevalence of computed tomography (CT). Identification
      of these lesions is indispensable for wedge resection performed by video-assisted
      thoracic surgery. Previous reports of marking techniques showed some failure and
      complications. We have developed a new marking technique and herein describe the
      efficacy of this technique: fluoroscopy-assisted thoracoscopic surgery after
      computed tomography-guided bronchoscopic barium marking. METHODS: Twenty patients
      underwent this procedure for 21 small peripheral pulmonary lesions approximately
      10 mm in size. RESULTS: All the lesions were successfully marked and identified
      during fluoroscopy-assisted thoracoscopy. They were resected with sufficient
      margins. There were no complications related to this procedure. The pathologic
      examination of these 21 lesions revealed primary lung cancer in 14, atypical
      adenomatous hyperplasia in four, a metastatic tumor in one, and a benign tumor in
      two. CONCLUSIONS: This procedure is both a reliable and minimally invasive
      technique in thoracoscopic wedge resection for small peripheral pulmonary
      lesions.

PMID- 11235686
TI  - Current management of postoperative chylothorax.
AB  - BACKGROUND: This study was performed to review our experience with postoperative
      chylothorax and describe our current approach. In addition, we wanted to estimate
      the impact of video-assisted thoracoscopic surgery (VATS) on our current
      management policy. METHODS: From January 1991 to December 1999, 12 patients
      developed chylothorax after various thoracic procedures. Their mean age was 61.5
      (range 31 to 80 years). The procedures were cardiac, aortic, and pulmonary
      operations. RESULTS: All patients were initially treated conservatively. In
      addition, 7 patients needed surgical intervention, including one thoracotomy and
      six VATS. The site of thoracic duct laceration was identified and treated with
      VATS in 4 patients. In 2 patients, the leak could not be localized by VATS, and
      fibrin glue or talcage were applied in the pleural space. All patients were
      discharged without recurrent chylothorax. CONCLUSIONS: VATS is an effective tool
      in the management of persisting postoperative chylothorax. Its easy use, low
      cost, and low morbidity rate suggest an earlier use of VATS in the treatment of
      postoperative chylothorax.

PMID- 11235687
TI  - Efficacy study of video-assisted thoracoscopic surgery pleurodesis for
      spontaneous pneumothorax.
AB  - BACKGROUND: This study aims to assess the efficacy of video-assisted
      thoracoscopic surgery pleurodesis in the treatment of spontaneous pneumothorax
      with particular reference to the rate of recurrence after abrasion pleurodesis
      and postoperative neuralgia. METHODS: One hundred one patients who underwent 109
      video-assisted thoracoscopic surgery pleurodesis procedures in the Austin &
      Repatriation Medical Centre between January 1992 and June 1998 were identified
      from a computerized database. The follow-up period was from 8 months to 7 years
      and 1 month (mean, 44.4 months). Patients were telephoned and asked as to whether
      recurrence occurred, and if so, when it occurred and how it was treated. They
      were asked to grade their current pain level from 0 to 6. RESULTS: Eighty-two
      patients were contacted, corresponding to 88 video-assisted thoracoscopic surgery
      pleurodesis procedures that were followed up (80.7%). There were five recurrences
      (5.7%). The pain level was rated as 0 in 64 cases (72.7%), 1 in 27 cases (23.9%),
      2 in 1 case (1.1%), and 3 in 2 cases (2.3%). CONCLUSIONS: These data suggest that
      video-assisted thoracoscopic surgery pleurodesis is a valid alternative to
      thoracotomy with pleurectomy for treatment of spontaneous pneumothorax with an
      acceptable recurrence rate and minimal amount of postoperative neuralgia.

PMID- 11235688
TI  - Tension pneumocephalus resulting from iatrogenic subarachnoid-pleural fistulae:
      report of three cases.
AB  - BACKGROUND: Symptomatic pneumocephalus may result from a cerebrospinal fluid leak
      communicating with extradural air. However, it is a rare event after thoracic
      surgical procedures, and its management and physiology are not widely recognized.
      METHODS: During the past 2 years, we have identified 3 patients who developed
      pneumocephalus after thoracotomy for tumor resection. Only 1 patient had a
      discernible spinal fluid leak identified intraoperatively. Two patients
      experienced delayed spinal fluid drainage from their chest tubes and subsequently
      developed profound lethargy, confusion, and focal neurologic signs. The third
      patient was readmitted to the hospital with a delayed pneumothorax and altered
      mental status. Radiographic imaging in all patients showed significant
      pneumocephalus of the basilar cisterns and ventricles. RESULTS: The first 2
      patients were managed by discontinuation of the chest tube suction and bedrest.
      The third patient underwent surgical reexploration and nerve root ligation. All 3
      patients had resolution of their symptoms within 72 hours. CONCLUSIONS:
      Pneumocephalus is a rare, but serious, complication of thoracotomy. Previous
      patients reported in the literature have been managed with reoperation to ligate
      the nerve roots. However, the condition resolved nonoperatively in 2 of our
      patients. Discontinuation of chest tube suction may be definitive treatment and
      is always the important initial management to decrease cerebrospinal fluid
      extravasation into the pleural space and allow normalization of neurologic
      symptoms.

PMID- 11235689
TI  - Successful retrieval and function of lungs from non-heart-beating donors.
AB  - BACKGROUND: Lung transplantation has been used effectively as a therapeutic tool
      in end-stage pulmonary diseases, but organ shortages have restricted its use.
      There is growing interest in alternative organ sources such as organs from
      circulation-arrested cadavers, so called non-heart-beating donors. METHODS: We
      examined the effects of postmortem rapid in situ cadaver lung cooling by
      bilateral chest cavity flushing (group 2) and by pulmonary artery flush through
      right heart catheterization followed by pleural cavity flushing (group 3) on
      pulmonary function and morphology in a rabbit non-heart-beating donor model. The
      results were compared with those in a control group of heart-beating donors
      (group 1). RESULTS: At the end of a 2-hour reperfusion period, there were no
      significant differences in mean pulmonary artery pressure, pulmonary vascular
      resistance, pulmonary compliance, arteriovenous oxygen, pulmonary wet to dry
      weight ratio, and lung morphology between the three groups. CONCLUSIONS: Our
      study demonstrates that using bilateral chest cavity flushing with or without
      pulmonary flush protects the function and morphology of cadaver lungs and renders
      them suitable for lung transplantation.

PMID- 11235690
TI  - Save a child's heart: we can and we should.
AB  - BACKGROUND: Congenital heart disease (CHD) causes the death of thousands of
      children in developing countries. At the Wolfson Medical Center (WMC), a
      prototype program has been developed to address this issue. METHODS: Since 1996,
      indigent children have been referred to the program, with the cooperation of
      partners in developing countries. The project's aims are to (a) train their
      medical personnel at WMC, (b) travel to participating countries to teach,
      evaluate patients, operate, and promote the development of local centers, and (c)
      treat children with CHD, at WMC, who lack a local option for care either due to
      prohibitive costs or unavailability. The project's personnel are state employees
      who volunteer to treat additional patients within the framework of their
      salaries, and community volunteers. RESULTS: The program has seven partner sites
      in six countries, including two provinces in China (Hebei and Gansu), Ethiopia,
      Moldova, Nigeria, the Palestinian Authority, and Tanzania. Five physicians and 10
      nurses have been trained from five participating countries. Over the past 4
      years, 11 teaching trips have been made abroad, and operations have been
      performed at four partner sites. A total of 386 patients have been operated on
      360 at WMC and 26 at other sites. There have been 17 (4.3%) acute deaths. Follow
      up is 92% complete with 3 late deaths reported. CONCLUSIONS: Hospital-based
      regional centers can be created to promote the care of children with CHD in
      developing countries. Good results and follow-up care can be provided with
      appropriate planning.

PMID- 11235691
TI  - Minimal sternotomy approach for congenital heart operations.
AB  - BACKGROUND: In recent years, minimal access cardiac operations have increased in
      application in both the adult and pediatric population. As our experience has
      grown with these approaches to atrial septal defect closure, we have expanded the
      same approach to the repair of more complex congenital heart disease. METHODS: At
      the Children's Hospital in Boston, from August 1996 to November 1999, a minimal
      sternotomy approach was used to surgically correct 104 children with congenital
      heart defects other than atrial septal defect. The approach, in most patients,
      consisted of a skin incision based over the xiphisternum, 3.5 to 5 cm in length,
      with division of the xiphoid only and elevation of the sternum by fixed
      retractor. All patients underwent cannulation for cardiopulmonary bypass through
      the great vessels in the chest using this same incision. The lesions corrected
      included ventricular septal defect in 41 patients, tetralogy of Fallot in 27,
      common atrioventricular canal in 15, mitral valve operation in 3.5, and other
      defects in 18 patients. There were 53 male and 51 female patients. Mean age at
      operation was 1.4 years (range, 2 weeks to 11 years). RESULTS: There were no
      deaths. The mean cardiopulmonary bypass time was 71 minutes (standard deviation,
      19 minutes), mean cross-clamp times 40.8 minutes (standard deviation, 13
      minutes), and length of stay 4.5 days (standard deviation, 1.9 days).
      Complications included transient atrioventricular block in 2 patients, pleural
      effusion requiring drainage in 4, and pericardial effusion in 3 patients. When
      compared to similar lesions repaired using a full sternotomy approach there was
      no difference in operating times and length of stay tended to be shorter in the
      minimal sternotomy group. CONCLUSIONS: A minimal sternotomy approach can be used
      to repair congenital cardiac lesions other than atrial septal defects. It gives
      good exposure, particularly for transatrial repairs, does not prolong ischemic
      times, and may lead to shorter hospital stay.

PMID- 11235692
TI  - Ministernotomy versus full sternotomy in congenital heart defects: a prospective
      randomized study.
AB  - BACKGROUND: Although the ministernotomy is extensively used in the repair of
      congenital heart defects all over the world, whether this approach has additional
      advantages over the conventional full sternotomy is not well established. This
      prospective study was designed to evaluate the effects of lower ministernotomy in
      the repair of congenital heart defects. METHODS: One hundred patients who
      underwent repair of atrial or ventricular septal defects were randomly divided
      into two groups: lower ministernotomy group (n = 50), and full sternotomy group
      (n = 50). The clinical indexes of each procedure were recorded and analyzed.
      RESULTS: The age, sex, and types of cardiac defects were comparable between the
      two groups. Ischemic times, bypass times, intensive care unit stay, and
      ventilation duration were similar in both groups. The procedure time (from skin
      to skin) was longer in the lower ministernotomy group than in the full sternotomy
      group (p < 0.001). There was less drainage in the lower ministernotomy group than
      in the full sternotomy group for the first 24 hours after operation (186 +/- 99
      mL/m2 versus 237 +/- 134 mL/m2, p = 0.03) but no significant difference in
      transfusions between the two groups. The hospital stay was shorter in the lower
      ministernotomy group than in the full sternotomy group (6.5 +/- 1.2 days versus
      7.5 +/- 1.8 days, p = 0.02). CONCLUSIONS: Ministernotomy is as safe and effective
      as a full sternotomy in the repair of simple congenital heart defects in older
      children and adults. Furthermore, this small incision reduces the postoperative
      drainage, shortens hospital stay, and provides better cosmetic results. Operative
      times are longer.

PMID- 11235693
TI  - Intraoperative stents to rehabilitate severely stenotic pulmonary vessels.
AB  - BACKGROUND: Patch enlargement of severe branch pulmonary artery stenosis (PAS) or
      pulmonary vein ostial stenosis (PVS) can be technically challenging. Recurrences
      are common and exposure may require long periods of cardiopulmonary bypass (CPB).
      METHODS: Since 1993, we performed 31 procedures on 27 patients with endovascular
      stents placed intraoperatively under direct surgical vision: 22 patients with
      tight PAS and 5 patients with PVS. Selection for intraoperative (vs
      catheterization laboratory) stent placement was prompted by: (1) the need for a
      concomitant cardiac surgical procedure (16 cases); (2) limited vascular access
      for catheterization laboratory stent placement (11 cases); or (3) "rescue" of
      patients with complications after attempted placement of stents (4 cases).
      RESULTS: In this group of very complex and challenging patients there were 5
      hospital deaths (hospital survival, 81%). Follow-up of survivors has ranged from
      1 month to 7 years (mean 2.8 +/- 1.7 years). There have been 3 late deaths (late
      "series" survival, 70%). No complication or death was related to stent placement.
      Surviving patients have had significant clinical improvement. Mean pulmonary
      gradient (postoperative vs preoperative echo) has fallen in all survivors and has
      decreased from a mean of 66 mm Hg preoperatively to 28 mm Hg postoperatively (p =
      0.01). All pulmonary arteries are appreciably enlarged and will be easier to deal
      with at a later date if necessary. One patient (DORV, HLHS ) with pulmonary vein
      stents has gone on to a successful Glenn procedure. The other two surviving
      patients with PV stents have occlusion of their proximal PVs on follow-up
      catheterization; thus only 1 of 5 patients with stents for PVS has had a
      successful outcome. Four patients have had repeat surgery. Stents have produced
      no impediment to subsequent surgical procedures, and the pulmonary arteries were
      easy to work with. CONCLUSIONS: Intraoperative stenting provides an attractive
      option for "rehabilitation" of pulmonary vessels. Direct vision insertion on CPB
      is extremely quick and immediately effective, limiting the CPB exposure required
      to treat this problem. Once stented, vessels remain open and are amenable to
      future surgical intervention as necessary. Outcome is better for patients with
      PAS versus those with PVS.

PMID- 11235694
TI  - Reoperative homograft right ventricular outflow tract reconstruction.
AB  - BACKGROUND: Homografts are implanted in the right ventricular outflow tract
      (RVOT) of children, with the knowledge that reoperation might be required. We
      reviewed 14 years of homograft RVOT reconstruction to assess the feasibility of
      homograft replacement and to determine risk factors for homograft survival.
      METHODS: From February 1985 through March 1999, 223 children (age 5 days to 16.9
      years) underwent primary RVOT reconstruction with an aortic or pulmonary
      homograft. Of these, 35 patients underwent homograft explant at the implanting
      hospital with insertion of a second homograft from 2 months to 13.3 years after
      the first implantation. The primary operation and reoperation patient groups were
      compared with regard to incidence of early death, late death, homograft-related
      intervention without explant, and homograft explant. RESULTS: Actuarial survival
      and event-free curves for initial and replacement homografts were not
      significantly different. Univariable analysis was performed for the following
      risk factors: weight (p < 0.0001), age (p < 0.003), homograft diameter (p <
      0.0001), homograft type (p < 0.01), surgery date (not significant [NS]), gender
      (NS), Blood Group match (NS), and type of distal anastomosis (NS). Multivariable
      analysis of significant univariable risks revealed small homograft diameter to be
      a significant risk factor (p < 0.001) for replacement. CONCLUSIONS: The RVOT
      homografts eventually require replacement. Patient and homograft survival for
      replacement homografts is similar to primary homografts. Reoperative homograft
      RVOT reconstruction is possible, with reasonably low morbidity and mortality.

PMID- 11235695
TI  - Open commissurotomy for critical isolated aortic stenosis in neonates.
AB  - BACKGROUND: The optimal management of critical aortic stenosis in early infancy
      remains controversial. The aim of this study was to assess the early and late
      outcomes following open surgical valvotomy for critical aortic stenosis in
      neonates and to provide a framework of data against which current results of
      other treatment approaches can be evaluated. METHODS: Eighteen consecutive
      neonates (mean age 9.2 days, range 1 to 26 days) undergoing an open valvotomy for
      critical isolated aortic stenosis (the standard treatment for this condition in
      our unit) between 1984 and 2000 were studied. The mean aortic valve gradient was
      79.4 mm Hg. Twelve neonates received prostaglandins and 10 received inotropic
      agents preoperatively. Follow-up was complete (mean 8.1 years, range 1 month to
      15 years). RESULTS: There was no operative mortality. At discharge, the mean
      aortic valve gradient was 37.2 mm Hg, with 6 patients having mild and 2 having
      moderate aortic regurgitation. Six patients required a reoperation; 3 of these
      had an aortic valve replacement at 9 to 11 years of age. Kaplan-Meier 5- and 10
      year freedoms from any aortic reoperation or reintervention were 85 and 55%,
      respectively; 5- and 10-year freedoms from aortic valve replacement were 100 and
      79%, respectively. A 14-year-old boy died from endocarditis 4 years following an
      aortic valve replacement in another unit. Kaplan-Meier 10-year survival was 100%.
      All survivors are in New York Heart Association I class and are leading normal
      lives. Their mean aortic valve gradient is 34.5 mm Hg, and none has significant
      aortic regurgitation. CONCLUSIONS: Open valvotomy for critical aortic stenosis in
      neonates carries a low operative risk and provides lengthy freedom from recurrent
      stenosis or regurgitation. Reoperations are inevitable, but aortic valve
      replacement can be delayed until the implantation of an adult-sized prosthesis is
      possible. Late survival is excellent. We consider open surgical valvotomy to be
      the treatment of choice for critical neonatal aortic stenosis.

PMID- 11235696
TI  - Outcome after repair of tetralogy of Fallot in the first year of life.
AB  - BACKGROUND: The purpose of this study was to evaluate the early and late outcome
      after repair of tetralogy of Fallot in the first year of life. METHODS: Between
      1974 and 2000, 89 consecutive infants with a mean age of 6.3 +/- 2.6 months
      (range, 15 days to 12 months) underwent repair of tetralogy of Fallot
      (ventricular septal defect and pulmonary stenosis) by one surgeon (J.L.M.). Three
      infants had previous palliative operations. Sixty-seven procedures were urgent or
      emergency. A transannular patch was inserted in 69 patients (77.5%). Follow-up
      was complete, averaging 13.4 +/- 5.6 years (range, 0 to 25.4 years). RESULTS:
      There was one operative death (1.1%). Mean right ventricular to left ventricular
      pressure ratio postoperatively was 0.4 +/- 1.1 (in 79 patients, < 0.5). Fourteen
      patients underwent reoperations or reinterventions. There were no reoperations
      for residual or recurrent ventricular septal defect. Kaplan-Meier freedom from
      reoperation or reintervention for any cause at 20 years was 85% +/- 4.4%, for
      relief of right ventricular outflow tract obstruction it was 94% +/- 3.1%, and
      for pulmonary valve replacement this was 95.4% +/- 2.6%. Use of a transannular
      patch did not significantly affect the need for reoperation or reintervention.
      There was one late death (leukemia). Kaplan-Meier 20-year survival was 97.8% +/-
      1.9%. On latest echocardiography, 42 patients had moderate pulmonary
      regurgitation, 4 had a right ventricular outflow tract gradient more than 40 mm
      Hg, and 86 had good biventricular function. Twelve-lead electrocardiography was
      performed in all and 24-hour electrocardiography in 61 patients. One patient
      (1.1%) exhibited late recurrent ventricular tachycardia requiring implantation of
      a defibrillator. The remaining 86 patients are in New York Heart Association
      class I with none of them receiving antiarrhythmic medications. CONCLUSIONS:
      These data strongly support the concept of early repair of tetralogy of Fallot.
      It is associated with an acceptable operative risk and a low incidence of
      significant arrhythmias, and provides long-term survival similar to that observed
      in the general population. Late complications may, however, develop, and long
      term follow-up for their early recognition is essential.

PMID- 11235697
TI  - Left atrial appendage insertion for right ventricular outflow tract
      reconstruction.
AB  - BACKGROUND: The left atrial appendage (LAA) may serve as an alternative to the
      pulmonary arterial wall for right ventricular outflow tract (RVOT) reconstruction
      without an extracardiac conduit. METHODS: Five consecutive patients with
      pulmonary atresia or severe stenosis underwent corrective (n = 4) or palliative
      (n = 1) RVOT reconstruction using an LAA insertion. Surgery was performed to
      treat tetralogy of Fallot, double-outlet right ventricle, or transposition of the
      great arteries. By inserting the LAA into the obstructed portion, the width of
      the posterior wall of the RVOT was 20 mm or more. The anterior half of the RVOT
      was then augmented with pericardial patch. RESULTS: There were no early or late
      postoperative deaths, and no major complications (arrhythmias, thrombo-embolic
      episodes, infective endocarditis, need for reoperation). The postrepair systolic
      right ventricular-to-systemic arterial pressure ratio was 0.61 +/- 0.26. Color
      Doppler flow mapping revealed that the reconstructed RVOT was nonobstructive and
      had nonturbulent flow. No thrombus or pseudoneointimal formation was observed in
      the RVOT. CONCLUSIONS: LAA insertion in the RVOT is an effective alternative to,
      or adjunct of, direct anastomosis. It offers several advantages, including fewer
      early and midterm complications and avoiding the use of an extracardiac conduit.

PMID- 11235698
TI  - Improved in-hospital mortality in women undergoing coronary artery bypass
      grafting. Northern New England Cardiovascular Disease Study Group.
AB  - BACKGROUND: Few studies have examined the changes in in-hospital mortality for
      women over time. We describe the changing case mix and mortality for women
      undergoing coronary artery bypass grafting (CABG) from 1987 to 1997 in northern
      New England. METHODS: Data were collected on 8,029 women and 21,139 men
      undergoing isolated CABG. The study consisted of three time periods (1987 to
      1989, 1990 to 1992, and 1993 to 1997) to account for regional efforts to improve
      quality of care that occurred during 1990 to 1992. RESULTS: Compared with 1987 to
      1989, women undergoing CABG in 1993 to 1997 were older, had poorer ventricular
      function, and more often required urgent or emergency operations. The crude and
      adjusted mortality rates for both women and men decreased significantly over
      time. The absolute magnitude of the change in adjusted rates was greater for
      women (3.1%) than for men (1.5%). Although women represented only 28% of the
      study population, the decrease in their mortality accounted for 44% of the total
      decrease in adjusted mortality during the study period. CONCLUSIONS: Over the
      last decade there has been a marked decrease in CABG mortality for women, despite
      a worsening case mix.

PMID- 11235699
TI  - Effects of race, with or without gender, on operative mortality after coronary
      artery bypass grafting: a study using The Society of Thoracic Surgeons National
      Database.
AB  - BACKGROUND: Although gender is known to be an independent predictor of 30-day
      operative mortality (OM) after coronary artery bypass grafting, the purpose of
      this study was to determine whether race-alone or in combination with gender
      affects OM. METHODS: For 1994 to 1996, The Society of Thoracic Surgeons database
      records for 441,542 coronary artery bypass grafting-only procedures were
      analyzed. Baseline annual multivariate models were built. Gender and race were
      added to each model. Risk-adjusted OM rates were then calculated for race,
      gender, and their combination. Patients were also stratified into groups of
      comparable predicted OM to allow for a direct comparison of risk-matched
      Caucasians and non-Caucasians. RESULTS: Of the procedures, 28.2% were on women
      and 8.5% on non-Caucasians. Overall, OM was 3.29%. Multivariate risk-adjusted OM
      varied by gender and race (p < 0.10). Risk-adjusted OM rates (with 95% confidence
      intervals) were 4.0% (3.9% to 4.1%) for females and 3.2% (3.2% to 3.3%) for
      males. Risk-adjusted OM rates were 3.9% (3.7% to 4.1%) for non-Caucasians and
      3.3% (3.2% to 3.3%) for Caucasians. Among equally risk-matched Caucasians and non
      Caucasians, non-Caucasians had significantly higher (p < 0.005) mortality among
      the lower risk subgroups (up to 10% predicted OM) but not among the higher risk
      subgroups. CONCLUSIONS: Race and gender are independent predictors of adverse
      outcome following coronary artery bypass grafting, holding all other risk factors
      constant.

PMID- 11235700
TI  - Effects of body size on operative, intermediate, and long-term outcomes after
      coronary artery bypass operation.
AB  - BACKGROUND: To investigate the role of body size, if any, on operative and longer
      term outcomes following coronary artery surgery. METHODS: A total of 3,560
      consecutive patients undergoing coronary artery bypass grafting from 1991 to
      1997, including 2,401 (67%) males and a mean +/- SD age of 63 +/- 10 years were
      ranked based on their body mass index (BMI). The association in these patients of
      preoperative, long-term, and economic data with variations in BMI were studied
      using regression analyses. Long-term survival was studied using 5-year Kaplan
      Meier survival analysis. RESULTS: Operative mortality, myocardial infarction,
      cerebrovascular accidents, blood transfusions, and length of hospital stay were
      all increased in the smallest patients (BMI < or = 24 kg/m2). Obesity did not
      increase adverse operative outcomes except for a greater rate of sternal wound
      infections occurring with increasing severity of obesity. Direct variable costs
      were lowest in patients clustered around normal BMI, with cost increasing
      similarly at low and high extremes. This effect was correlated with similar BMI
      effects on ventilatory and intensive care requirements. Excluding operative
      mortality, 5-year survival trends were similarly worse for the smallest (BMI < or
      = 24) and most severely obese (BMI > 34) patients. Mild obesity (BMI > or = 30 to
      BMI < 34) did not affect long-term survival. CONCLUSIONS: Among study patients,
      immediate operative outcomes were adversely affected by small body size, which
      reflected older age (66 +/- 10 years) and an exaggerated adverse impact of
      cardiopulmonary bypass. Younger age and smaller effects of cardiopulmonary bypass
      lead to better operative outcomes in the obese. Long-term outcomes were, however,
      suboptimal in severely obese patients although that group was the youngest (60 +/
      10 years). In addition to their large body habitus, other factors, including
      substantial prevalence of diabetes, insulin dependence and hypertension, probably
      played a significant role in the poor long-term outcome in the severely obese.

PMID- 11235701
TI  - Survival after transmyocardial laser revascularization in relation to nonlasered
      perfused myocardial zones.
AB  - BACKGROUND: Transmyocardial laser revascularization for severe diffuse coronary
      artery disease reduces angina significantly. The effect on survival, however, is
      questionable, and risk factors are not adequately addressed. Considering that
      transmyocardial laser revascularization channels do not remain patent for
      improving direct myocardial blood supply, other variables such as perfusion
      through open native or grafted vessels in remote non-transmyocardial laser
      revascularization areas are probably more important for survival. This hypothesis
      is the subject of the study. METHODS: Transmyocardial laser revascularization was
      performed with a CO2 laser system in 63 patients between October 1995 and
      December 1997. Patients received transmyocardial laser revascularization alone or
      in combination with coronary artery bypass grafting. The heart was divided into
      three perfusion zones as determined by the three major coronary arteries.
      Patients were divided into three groups according to the number of zones that
      were perfused by either a native coronary artery or a patent bypass graft: group
      1 (n = 9), none; group 2 (n = 24), one; and group 3 (n = 30), two. Follow-up was
      performed at 3, 6, 12, 24, and 36 months and was 100% complete. Mean latest
      follow-up was 26.2 months, minimal follow-up of survivors was at least 12 months.
      RESULTS: Overall mortality was remarkably higher in group 1 (77.8%) compared with
      group 2 (20.8%, p = 0.005) and group 3 (13.3%, p = 0.001). Hospital mortality was
      22.2% in group 1, 0% in group 2, and 3.3% in group 3. Late mortality was also
      higher in group 1 (55.5% versus 20.8%, and versus 9.9%, respectively). Cardiac
      deaths were more frequent in group 1 (55.5% versus 12.5% in group 2, p = 0.02,
      and versus 9.9% in group 3, p = 0.009). The number of perfused myocardial zones
      showed a significant influence for survival (p = 0.002). CONCLUSIONS: These data
      give some directional evidence that survival seems to be beneficially affected by
      the number of nonlasered perfused myocardial zones through native vessels or
      grafts in patients undergoing transmyocardial laser revascularization.

PMID- 11235702
TI  - Target vessel revascularization without cardiopulmonary bypass in elderly high
      risk patients.
AB  - BACKGROUND: Coronary artery bypass grafting in patients over 75 years is
      associated with high operative risk. Target vessel revascularization without
      cardiopulmonary bypass is a promising option for highly selected, older patients.
      However, the outcome remains uncertain. METHODS: We investigated 44 patients over
      75 years, matched for preoperative risk and left ventricular function, who
      underwent coronary artery bypass grafting either with or without cardiopulmonary
      bypass (CPB). We analyzed patients characteristics, Parsonnet score, EuroSCORE,
      short as well as midterm outcome and quality of life (freedom from recurrence of
      angina, anti-anginal therapy, sf36 test). RESULTS: Perioperative mortality was
      higher in the patient group operated with CPB (15.9) as compared to patients
      operated without CPB (4.5%, p = 0.0226). Patients operated with cardiopulmonary
      bypass received more grafts (3.1 +/- 0.1) than patients operated without
      cardiopulmonary bypass (1.6 +/- 0.1, p = 0.0001) and and were more likely to
      undergo complete revascularization (with CPB 100%, without CPB 63.6%, p =
      0.0010). Perioperative complications were more frequent and midterm survival was
      worse in the patient group operated with CPB (log rank p = 0.0228). Quality of
      life was comparable in both groups. CONCLUSIONS: The concept of incomplete target
      vessel revascularization of the culprit lesion seems to be a promising option for
      selected high-risk patients, predominantly due to lower perioperative mortality.

PMID- 11235703
TI  - Coronary artery bypass grafting in patients on chronic hemodialysis: surgical
      outcome in diabetic nephropathy versus nondiabetic nephropathy patients.
AB  - BACKGROUND: The presence of diabetes mellitus adversely affects the late survival
      of patients undergoing coronary artery bypass grafting (CABG). The purpose of
      this study is to clarify the role of diabetic nephropathy on outcomes of a group
      of patients on chronic hemodialysis undergoing CABG. METHODS: Between April 1984
      and July 1999, 45 patients on chronic hemodialysis underwent CABG. Forty-three
      had conventional CABG and 2 had off-pump CABG. There were 37 males and 8 females,
      and the mean age was 57 years (43 to 76 years). Twenty-one patients had diabetic
      nephropathy (group D) and 24 had nondiabetic nephropathy (group ND). Early and
      late results were determined in both groups. RESULTS: Early outcome was not
      significantly different between the groups. There was no hospital mortality,
      stroke, or requirement for prolonged mechanical ventilation (>24 hours) in either
      group. No patients in group D, and only 1 (4.2%) in group ND had low cardiac
      output syndrome. The difference in the incidence of arrhythmias (23.8% in group D
      and 25% in group ND), wound infections (9.5% in group D and 8.3% in group ND),
      and delayed tamponade (5% in group D and 12.5% in group ND) was not statistically
      significant. However, late results differed significantly between the two groups.
      Actuarial survival (Kaplan-Meier) at 5 and 9 years was 22.9% and 11.5% in group D
      and 89.1% and 45.7% in group ND (p = 0.01), respectively. Similarly, the cardiac
      event-free rate at the same intervals was 50.4% and 0% for group D and 100% and
      65.8% for group ND (p = 0.001), respectively. CONCLUSIONS: Using present
      technology, CABG can be done in patients on chronic hemodialysis with acceptable
      early mortality and morbidity. Late results in patients with diabetic nephropathy
      on hemodialysis are not as favorable as their nondiabetic cohort.

PMID- 11235704
TI  - Effect of age on outcome of bilateral skeletonized internal thoracic artery
      grafting.
AB  - BACKGROUND: Elderly patients are considered to be at higher risk for coronary
      artery bypass grafting. Surgical techniques of arterial myocardial
      revascularization without vein grafts were primarily reserved for the young. This
      report evaluates the impact of age on the outcome of 634 consecutive patients who
      underwent double skeletonized internal thoracic artery grafting between April
      1996 and December 1997. METHODS: Patients were stratified into five age groups:
      One hundred ninety-six were less than 60 years of age, 98 between 60 and 65
      years, 132 between 65 and 70 years, 116 between 70 and 75 years, and 92 were
      older than 75 years. The groups did not differ with regard to preoperative risk
      factors. RESULTS: Hospital mortality was 2.5% (n = 16). Mortality of urgent and
      elective operations was 1.6%, and that of emergency operations was 9.7% (p <
      0.001). There were 7 (1.1%) myocardial infarctions, 9 strokes (1.4%), and 10 deep
      sternal wound infections (1.6%). Using the Mantel-Haenszel test, there was no
      relation between age and hospital mortality, myocardial infarctions, strokes, or
      sternal infections. A correlation was found between advanced age and early
      unfavorable events (6.7%, 7.2%, 12.9%, 15.5%, and 15.2% in corresponding age
      groups, p < 0.003), and late mortality (0.6%, 1%, 1.5%, 4.3%, and 9.8%,
      respectively, p < 0.01). However, early return of angina was lower (2.6%, 1%,
      0.8%, 0.9%, and 0%, p < 0.06). CONCLUSIONS: This retrospective, nonrandomized
      study suggests that older age is not a risk factor for operative mortality in
      patients undergoing coronary artery bypass grafting with double skeletonized
      internal thoracic arteries. Apart from avoiding morbidity associated with leg
      incisions, older patients showed an interesting trend toward lower rates of
      angina return. Older patients, however, sustained increased perioperative
      morbidity and late mortality rates.

PMID- 11235705
TI  - Does routine use of the radial artery increase complexity or morbidity of
      coronary bypass surgery?
AB  - BACKGROUND: Despite increasing data supporting its use, the uptake of radial
      artery coronary bypass grafting by most surgeons remains low. This may partly be
      from perceptions that it increases risk or complexity of coronary surgery.
      METHODS: Data on 151 patients who had radial grafts are compared with 179
      concurrent nonrandomized controls that underwent conventional surgery using
      saphenous vein. Additionally, telephone interviews were conducted on 127 radial
      recipients to assess subjective outcome. RESULTS: Cardiopulmonary bypass and
      cross-clamp times were similar in both groups (72 versus 74 minutes and 20 versus
      22 minutes). Morbidity was comparable (mortality 1% versus 2%; cerebral vascular
      accident 1% versus 2%; sternal infection 1% versus 2%; resternotomy 4% versus
      6%). Of 127 patients contacted, 41 (32%) reported that they had experienced
      parasthesia, and 65 (51%) reported numbness related to radial harvest; of these,
      75% reported their symptoms as resolved or resolving. Early angiography performed
      in 36 patients revealed a radial patency rate of 92%. CONCLUSIONS: Concerns about
      increased morbidity and mortality should not hinder adoption of radial artery
      grafting.

PMID- 11235706
TI  - Clinical results with left axillary to left anterior descending coronary artery
      bypass.
AB  - BACKGROUND: The minimally invasive direct coronary artery bypass procedure is not
      feasible if the left internal mammary artery has been used or has inadequate
      flow. We have applied a modified minimally invasive direct coronary artery bypass
      procedure, which uses a graft from the left axillary artery to the left anterior
      descending coronary artery in such situations. METHODS: The graft is anastomosed
      to the left axillary artery adjacent to the clavicle and tunneled underneath the
      vein, where it enters the thorax through the first interspace and courses to the
      left anterior descending coronary artery along the mediastinum. RESULTS: Since
      1997 we have used this operation in 22 patients with a mean age of 70 years
      (range, 52 to 83 years). All patients were high-risk candidates because of
      advanced age (70 +/- 7 years), depressed left ventricular function (mean left
      ventricular ejection fraction, 38% +/- 6%), or previous heart operation (20 of
      22, 91%). Conduits for the graft were saphenous vein (n = 18) or radial artery (n
      = 4). Ten patients were extubated in the operating room, and the mean duration of
      mechanical ventilation was 5.8 +/- 6 hours. There was one operative death (1 of
      22, 4.5%). The mean length of intensive care unit and hospital stay was 1.5 days
      (range, 1 to 6 days) and 6 days (range, 2 to 15 days), respectively. At a mean
      follow-up of 6 months, all discharged patients are alive and functionally
      improved. None have required surgical or catheter-based revascularization of the
      left anterior descending coronary artery. CONCLUSIONS: The left axillary artery
      to left anterior descending coronary artery graft should be considered for high
      risk patients in whom a minimally invasive direct coronary artery bypass
      procedure is not possible.

PMID- 11235708
TI  - Serial change in the atrial transport function after the radial incision
      approach.
AB  - BACKGROUND: The left atrial transport function recovers slowly over several
      months after the maze procedure (Maze), but remains at a low level even during
      the long-term postoperative period. Because the Maze leaves an insufficient left
      atrial transport function, patients may still be prone to thromboembolism after
      the Maze. The radial incision approach (Radial) has been shown to preserve
      greater atrial transport function than does the Maze in the early postoperative
      period. METHODS: To examine the serial change in the atrial transport function
      after the Radial, out of 32 patients who underwent the Radial, 15 patients were
      assessed by transthoracic Doppler echocardiography 1, 3, 6, and 12 months after
      surgery. The atrial filling fraction and peak A/E velocity ratio were determined
      from the flow-velocity spectra across the mitral and tricuspid valves. The
      incidence of thromboembolic events was examined in 21 patients who were followed
      for more than 3 months after the Radial. The data were compared with data
      obtained from 13 patients after (41 +/- 6 months) the Maze III procedure.
      RESULTS: The left atrial transport function after the Radial increased within 3
      months to a significantly greater level than did that after the Maze in the
      longterm. The atrial filling fraction was 28.2% +/- 7.9% at 3 months after the
      Radial and 15.1% +/- 4.0% at 41 months after the Maze (p < 0.01). The peak A/E
      ratio was 0.52 +/- 0.18 at 3 months after the Radial and 0.25 +/- 0.07 at 41
      months after the Maze (p < 0.01). This increased atrial transport function was
      maintained for an extended period after the Radial. There were no thromboembolic
      events in any of the patients after the Radial or Maze, irrespective of
      postoperative anticoagulant therapy. CONCLUSIONS: The Radial approach prevents
      thromboembolism by restoring sufficient atrial transport function more
      effectively and faster than does the Maze.

PMID- 11235707
TI  - Myocardial preservation during coronary surgery with and without cardiopulmonary
      bypass.
AB  - BACKGROUND: There is increased interest in coronary artery bypass grafting (CABG)
      without cardiopulmonary bypass (CPB), although the preservation of the myocardium
      under such circumstances has not been properly investigated. The aim of this
      randomized study was to compare the changes in myocardial metabolism during CABG
      with and without CPB. METHODS: Myocardial energy metabolism and tissue injury
      during CABG was monitored in a series of 22 patients (11 with and 11 without
      CPB). RESULTS: The maximum myocardial lactate production was significantly higher
      (p = 0.02) in the group operated with CPB (0.56 mmol/L) than without it (0.17
      mmol/L). A similar phenomenon was seen in the transcardiac pH differences (0.085
      and 0.034 with and without CPB, p = 0.007). The postoperative peak values of
      creatine kinase-MB mass (15.1 vs 6.3 microg/L) and troponin I (13.8 vs 5.2
      microg/L) were significantly higher (p < 0.001 and p = 0.008) with than without
      CPB. CONCLUSIONS: CABG on a beating heart is associated with better myocardial
      energy preservation and less myocardial damage compared with conventional CABG
      with CPB and intermittent antegrade mild hypothermic blood cardioplegia.

PMID- 11235709
TI  - Clinical analysis of results of a simple left atrial procedure for chronic atrial
      fibrillation.
AB  - BACKGROUND: We have performed a simple left atrial procedure for eliminating
      chronic atrial fibrillation (AF) associated with mitral valve disease. This
      article analyzes the midterm results of this procedure. METHODS: Thirty-two
      patients were enrolled in this study concomitant with mitral valve operations.
      Patients were divided into two groups (AF- and AF+). We examined the efficacy of
      this operation and atrial function for more than 12 months of follow-up. RESULTS:
      In a total of 98.5 patient years of follow-up, AF was absent 3 years after
      operation in 74%. Of preoperative and intraoperative variables, only long
      duration o

PMID- 11235710
TI  - Tricuspid valve supra-annular implantation in adult patients with Ebstein's
      anomaly.
AB  - BACKGROUND: Tricuspid valve supra-annular implantation (TVSI) has been performed
      for adult patients with Ebstein's anomaly at our hospital for several decades.
      TVSI is characterized by reliable reduction of tricuspid annulus size without
      affecting the conduction system; by prevention of residual tricuspid
      regurgitation (RTR) through preservation of the native tricuspid valve; and by
      implantation of the bioprosthesis at a supra-annular site. METHODS: Ten adult
      patients with Ebstein's anomaly underwent TVSI. The right ventricular diameter
      and residual tricuspid regurgitation were evaluated by echocardiography
      preoperatively, at discharge, 1 year after the operation, and over the long term
      (12.4 +/- 5.5 years). Actuarial survival rate, actuarial freedom from structural
      valve deterioration rate, and postoperative occurrence of arrhythmia were also
      evaluated. RESULTS: The actuarial survival rate at 19 years was 76 +/- 15%.
      Tricuspid regurgitation disappeared in 8 patients just after operation. Right
      ventricular diameter was significantly smaller at discharge than preoperatively
      (63 +/- 11 vs 37 +/- 9, p < 0.01), and there were no significant differences
      between values at discharge and at follow-up. The actuarial freedom from
      structural valve deterioration rate and the reoperation rate were both 100%.
      There were no fatal complications related to arrhythmia or thromboembolism.
      CONCLUSIONS: TVSI is useful for adult patients with Ebstein's anomaly. The
      absence of complications related to fatal arrhythmia and thromboembolism, good
      durability of the bioprosthesis, and a simple operative procedure are merits of
      this therapy.

PMID- 11235711
TI  - Sinus node function after mitral valve surgery using the superior septal
      approach.
AB  - BACKGROUND; Sinus node function after the superior septal approach (SSA) in
      mitral valve surgery is controversial. We assessed sinus node function after this
      approach based on electrophysiological examinations and electrocardiographic
      change. METHODS: Forty-six patients underwent successful mitral valve surgery via
      the SSA. Preoperatively, 25 patients were in atrial fibrillation (AF), 20 were in
      normal sinus rhythm (SR), and 1 patient was paced. Thirteen patients who
      demonstrated no sinus node dysfunction preoperatively underwent postoperative
      electrophysiological studies. Peripostoperative cardiac rhythm was monitored
      using a portable four-lead electrocardiograph, and late cardiac rhythm was
      examined using standard 12-lead electrocardiography in the outpatient clinic.
      RESULTS: Twelve of 20 patients with preoperative SR experienced early
      postoperative supraventricular arrhythmias, but all spontaneously recovered SR.
      Electrophysiological studies revealed a basic cycle length of 767 +/- 74 ms,
      sinoatrial conduction time of 72 +/- 34 ms, sinus node recovery time of 1,119 +/-
      139 ms, and corrected sinus node recovery time of 349 +/- 114 ms, thus
      demonstrating a lack of sinus node dysfunction. During the postoperative period
      (34 +/- 24 months), 2 of the 20 patients with preoperative SR developed
      persistent AF, and 3 of the 25 patients with preoperative AF achieved normal SR.
      CONCLUSIONS: The SSA does not appear to cause longterm adverse effects on sinus
      node function, although temporary effects may occur.

PMID- 11235712
TI  - Cardiac surgery in the octogenarian: evaluation of risk, cost, and outcome.
AB  - BACKGROUND: Nationwide, cardiac surgery is being performed more frequently in
      patients aged 80 years and older. METHODS: One hundred four octogenarians
      undergoing a variety of heart-lung procedures were prospectively studied between
      1995 and 1998 for comparison with similar patients aged 65 to 75 years (n = 351).
      RESULTS: Octogenarians were more likely to be of female gender, and be
      nondiabetic than the younger group. The 30-day mortality rate for patients aged
      65 to 75 years was 3.4% (12 of 351 patients), versus 13.5% (14 of 104) for
      patients aged 80+ (p = 0.0004), which ranged from 2% (1 of 50) in nonemergent
      coronary artery bypass grafting to 75% (3 of 4) in double valve procedures.
      Complications occurring more frequently in octogenarians were severe low output
      state, reintubation, and atrial fibrillation. Elders experienced a longer
      intensive care (69.2 versus 43.3 hours, p = 0.002) and postoperative stay (10.09
      versus 7.45 days, p = 0.001), and were discharged to a skilled nursing facility
      more often than younger patients (47% versus 21.1%, p = 0.0001). Total direct
      costs were $4,818 higher in the octogenarian group (p = 0.0007). CONCLUSIONS:
      Although emergency operations and complex procedures carried high risks for the
      octogenarian, the majority of these patients can be offered operation with short
      term morbidity, mortality, and resource use that only modestly exceeds that of
      younger patients.

PMID- 11235713
TI  - Aortic valve replacement in geriatric patients: determinants of in-hospital
      mortality.
AB  - BACKGROUND: Aortic valve replacement is a common procedure in elderly patients.
      There has been a great deal of controversy about the risks associated with early
      mortality. Uncertainty of the risk associated with a small valve continues to
      remain controversial. This study was designed to identify the risk factors
      influencing early mortality and establish an accurate model for the prediction of
      in-hospital mortality. METHODS: One hundred eighty septuagenarians and
      octogenarians (58% women; mean age, 76 +/- 4.7 years) underwent primary isolated
      aortic valve replacement between 1986 and 1997. There was an overall mortality of
      16.7% (n = 180). Patients with a body surface area less than 1.8 m2 had an in
      hospital mortality of 23.2% (n = 95) compared with 8.1% (n = 74; p = 0.009) for
      patients with a body surface area of 1.8 m2 or more. Patients with a
      cardiopulmonary bypass time of less than 100 minutes experienced an early
      mortality of 8.9% (n = 56) compared with a 10.2% (n = 59) early mortality for
      patients on bypass time between 100 and 124 minutes and a 29.6% (n = 64) early
      mortality in patients with a pump time longer than 124 minutes (p = 0.040).
      RESULTS: Multivariate logistic regression analysis identified small body surface
      area and long cardiopulmonary bypass time as independent risk factors. A higher
      mortality was seen in female patients and patients receiving smaller valves.
      However, there was a strong correlation between small body surface area, small
      valve size, and female gender. CONCLUSIONS: Small body surface area and long
      cardiopulmonary bypass time are two independent risk factors in early mortality
      for elderly patients undergoing primary isolated aortic valve replacement. The
      use of small valves does not influence early mortality.

PMID- 11235714
TI  - Outcome and follow-up of aortic valve replacement with the freestyle stentless
      bioprosthesis.
AB  - BACKGROUND: The aim of this study was to determine the morbidity, mortality, and
      hemodynamics after implantation of the Freestyle stentless bioprosthesis in the
      aortic position. METHODS: A total of 280 patients were operated on from June 1993
      to July 1999 as part of a multicenter investigation. Factors influencing hospital
      mortality and long-term survival were assessed by logistic regression and Cox
      proportional hazards analysis. Patients were evaluated postoperatively at
      discharge, at 3 to 6 months, and yearly by clinical examination and color flow
      Doppler echocardiography. RESULTS: Hospital mortality in this group was
      relatively high (9.6%). Logistic regression analysis showed that cross-clamp
      time, age, myocardial infarction, diabetes, left ventricular hypertrophy,
      coronary artery disease, New York Heart Association class III or IV and female
      gender were the independent predictive factors. According to the Kaplan-Meier
      method, the 4-year survival for hospital survivors was 94%. In the multivariate
      Cox proportional hazard analysis, only coronary artery disease proved to be
      prognostic. During follow-up, 11 patients developed paravalvular leakage due to
      prosthetic dehiscence at the side of the noncoronary cusp. Performance of the
      prosthesis as assessed by echocardiography was excellent. Mean gradient decreased
      significantly between discharge and follow-up at 3 to 6 months. At 1-year follow
      up trivial regurgitation was found in 6 patients (3%) and mild regurgitation in 4
      (2%). Regurgitation did not increase with time. The effective orifice area
      increased significantly from discharge to follow-up at 3 to 6 months.
      CONCLUSIONS: Hospital mortality after implantation of a stentless bioprosthesis
      was higher compared to conventional prosthesis. A high incidence of prosthesis
      dehiscence at the proximal suture line was found, which was probably due to
      technique. Hemodynamic performance up to 3 years showed low transvalvular
      gradients. There is echocardiographic evidence for reduction of left ventricular
      hypertrophy and improvement of left ventricular function.

PMID- 11235715
TI  - Hemodynamic evaluation of 19-mm Carpentier-Edwards pericardial bioprosthesis in
      aortic position.
AB  - BACKGROUND: The aortic Carpentier-Edwards pericardial bioprosthesis offers good
      long-term clinical outcomes with a low rate of structural deterioration. However,
      little in vivo hemodynamic data is available for this bioprosthesis. METHODS: To
      determine the hemodynamic performance of the 19-mm Carpentier-Edwards pericardial
      valve, both cardiac catheterization and dobutamine stress echocardiography were
      electively performed in 10 patients. The mean age at the study was 71.6 +/- 4.4
      years and the mean body surface area was 1.39 +/- 0.11 m2. The peak-to-peak
      gradient, instantaneous peak gradient, mean gradient, and valve orifice area were
      measured by standard cardiac catheterization. The Doppler-derived gradients and
      valve orifice area were also measured both at rest and during dobutamine
      infusion. RESULTS: The average peak-to-peak gradient, instantaneous peak
      gradient, mean gradient, and valve orifice area measured by catheterization were
      13.0 +/- 5.4 mmHg, 28.5 +/- 7.7 mmHg, 12.0 +/- 4.9 mmHg, and 1.55 +/- 0.45 cm2,
      respectively. The peak and mean Doppler gradients, and valve orifice area by
      resting echocardiography were 27.7 +/- 9.5 mmHg, 12.3 +/- 4.8 mmHg, and 1.39 +/-
      0.26 cm2, respectively. At a dosage of 10 microg/kg/min of dobutamine, the mean
      Doppler gradient rose mildly to 22.2 +/- 4.8 mmHg, while the cardiac output
      increased from 4.49 +/- 0.44 to 6.64 +/- 0.87 L/min. The valve orifice area
      during the 10 microg/kg/min dobutamine infusion (1.55 +/- 0.25 cm2) was
      significantly larger than its value at rest (p < 0.05). CONCLUSIONS: With
      acceptable hemodynamic performance, use of the aortic 19-mm Carpentier-Edwards
      pericardial valve is a reliable option for elderly patients with a small annulus.

PMID- 11235716
TI  - Fungal left ventricular assist device endocarditis.
AB  - BACKGROUND: Infection remains as the most serious complication and represents a
      significant threat to patients during long-term mechanical circulatory support.
      Fungal infection is a particularly worrisome complication and left ventricular
      assist device (LVAD) endocarditis does pose a serious threat. METHODS: One
      hundred and sixty-five patients underwent TCI Heartmate LVAD implantation between
      July 1991 and December 1999 at our institution. Detailed medical records were
      kept prospectively for all patients, and a variety of infection-related endpoints
      were analyzed on patients with fungal LVAD endocarditis. RESULTS: Thirty-seven
      patients (22%) developed fungal infections during LVAD support. Five (3%) of
      those met our criteria for the diagnosis of fungal LVAD endocarditis. Microbial
      portals of entry were identifiable in all cases. Infections were managed
      successfully in 4 patients (80%). CONCLUSIONS: The successful management of
      fungal LVAD endocarditis currently requires early recognition of potentially
      nonspecific signs and symptoms, and timely institution of antifungal therapy. In
      some cases with device-specific manifestations of LVAD endocarditis, device
      removal and replacement is necessary. In patients with clinical manifestations of
      sepsis and fungal driveline site or pocket infections without positive blood
      culture, urgent transplantation may be the appropriate management. In the setting
      of shortage in the donor supply, device removal and replacement is necessary.

PMID- 11235717
TI  - Shelhigh No-React porcine pulmonic valve conduit: a new alternative to the
      homograft.
AB  - BACKGROUND: The Shelhigh No-React pulmonic valve conduit is a new porcine conduit
      that is glutaraldehyde-treated and detoxified using a proprietary heparin
      process. In our institution it has been implanted in 25 patients. The aim of this
      present contribution is to evaluate the short-term follow-up after its
      implantation. METHODS: From November 1997 to August 1999, 25 patients (mean age,
      20.2 years; range, 0.6 to 28.3 years) were operated on using this conduit.
      Seventeen patients underwent a Ross procedure for aortic valve disease, with the
      conduits implanted in anatomic position; 6 patients underwent right ventricular
      outflow tract reconstruction; 2 patients underwent the Rastelli operation. The
      follow-up was complete. Preoperative and postoperative two-dimensional
      echocardiography data were collected. RESULTS: There were two non-conduit-related
      deaths. Two conduits needed to be exchanged because of an increase in the
      gradient. Overall, all patients were improved in terms of New York Heart
      Association class. Comparison of preoperative and postoperative two-dimensional
      echocardiography gradient showed significant improvement. At the 30-month follow
      up, no calcification was seen on the explanted conduits or on the two-dimensional
      echocardiography, although many of the patients are children. CONCLUSIONS: The
      Shelhigh conduits seem to be an alternative to homograft especially in infants.
      These experiences are preliminary, and longer follow-up is required.

PMID- 11235718
TI  - A novel strategy of decoy transfection against nuclear factor-kappaB in
      myocardial preservation.
AB  - BACKGROUND: Nuclear factor-kappaB (NFkappaB) is critical for the transcription of
      multiple genes involved in myocardial ischemia-reperfusion injury. Therefore, we
      hypothesized that blocking NFkappaB would attenuate ischemia-reperfusion injury
      after prolonged myocardial preservation, resulting in an improvement in cardiac
      function. METHODS: Double-stranded oligodeoxynucleotides with a specific affinity
      for NFkappaB (NFkappaB decoy group) or a scrambled decoy group were transfected
      into rat hearts using a hemagglutinating virus of Japan-liposome method. After 16
      hours of preservation in Euro-Collins solution at 4 degrees C, the cardiac grafts
      were heterotopically transplanted into recipient rats of the same strain.
      RESULTS: Fluorescein isothiocyanate staining showed introduction of double
      stranded oligonucleotides into the nuclei of endothelial cells and
      cardiomyocytes. After 1 hour of reperfusion the NFkappaB decoy group showed
      significantly higher degrees of recovery of left ventricular function as well as
      significantly lower levels of serum creatine phosphokinase, myocardial water
      content, tissue IL-8, and neutrophil infiltration than did the scrambled decoy
      group (p < 0.05). CONCLUSIONS: Gene transfection of the NFkappaB decoy attenuates
      ischemia-reperfusion injury after prolonged heart preservation. As a result, this
      method appears to be a novel strategy for enhanced myocardial preservation.

PMID- 11235720
TI  - Effects of potassium channel opener aprikalim on the receptor-mediated
      vasoconstriction in the human internal mammary artery.
AB  - BACKGROUND: Arterial grafts for coronary artery bypass grafting such as the
      internal mammary artery (IMA) may develop spasm perioperatively. The purpose of
      this study was to investigate the effects of the potassium channel opener,
      aprikalim, on the receptor-mediated vasoconstriction in the human IMA in vitro.
      METHODS: We studied 160 IMA rings taken from coronary artery surgery in organ
      baths. The interaction between aprikalim and four vasoconstrictors 5
      hydroxytryptamine (5-HT), norepinephrine (NE), endothelin-1 (ET-1), and
      angiotensin II (AII) was investigated in two ways. RESULTS: Aprikalim relaxed IMA
      rings precontracted by the vasoconstrictors to 66.40 +/- 5.9% for 5-HT (EC50: 
      6.78 +/- 0.26 LogM), 57.40 +/- 5.5% for NE (-6.54 +/- 0.39 LogM), 81.00 +/- 6.7%
      for ET-1 (-6.58 +/- 0.26 LogM), and 93.90 +/- 2.5% for AII (-7.80 +/- 0.23 LogM).
      The relaxation in endothelium-denuded rings contracted by AII was similar to that
      in the endothelium-intact rings. The relaxation was attenuated by glibenclamide
      (3 microM) in 5-HT or NE-precontracted IMA. Pretreatment with aprikalim at 1
      microM depressed AII-induced contraction (33.20 +/- 7.5% versus 59.70 +/- 7.3%, p
      < 0.01) but only shifted the curves rightward for 5-HT or NE (EC50 3.1 or 4.3
      folds higher, p < 0.05), whereas at 30 microM it also significantly depressed the
      maximal contraction for 5-HT (35.70 +/- 4.9% versus 103.30 +/- 9.8%, p < 0.001)
      and NE (90.60 +/- 15.6% versus 125.60 +/- 7.9%, p < 0.05). In contrast, aprikalim
      did not significantly depress the contraction induced by ET-1 (p > 0.05).
      CONCLUSIONS: We conclude that aprikalim has vasorelaxant effects on IMA and the
      effect is vasoconstrictor-selective and endothelium-independent. Aprikalim may
      provide clinically useful vasorelaxant effects in coronary bypass surgery.

PMID- 11235719
TI  - Cardiac ischemic preconditioning improves lung preservation in valve replacement
      operations.
AB  - BACKGROUND: Previous work has shown that cardiac ischemic preconditioning reduces
      cardiac reperfusion injury. We investigated whether cardiac ischemic
      preconditioning can improve lung preservation in patients who undergo valve
      replacement. METHODS: Forty patients with rheumatic heart disease requiring valve
      replacement were randomly divided into two groups. Twenty patients received two
      cycles of 3 minutes of aortic cross-clamping and 2 minutes of reperfusion before
      cardioplegic arrest (group IP), and 20 patients underwent 10 minutes of
      cardiopulmonary bypass (group C, control group). Blood samples from the pulmonary
      vein were collected to measure levels of polymorphonuclear leukocytes, superoxide
      dismutase, malonedialdehyde, and thromboxane B2, and arterial oxygen tension.
      Blood samples from the coronary sinus were used to measure calcitonin gene
      related peptide values. Hemodynamic data were recorded by a pulmonary artery Swan
      Ganz catheter. Lung tissue was collected after 1 hour of reperfusion to evaluate
      morphology. Clinical outcome data were recorded. RESULTS: In group C
      (cardiopulmonary bypass and cardioplegic arrest), the levels of polymorphonuclear
      leukocytes, thromboxane B2, malonedialdehyde, and calcitonin gene-related peptide
      were increased after 1 hour of reperfusion, whereas the value for superoxide
      dismutase was decreased. In group IP, preconditioning attenuated the increase in
      polymorphonuclear leukocytes, thromboxane B2, and malonedialdehyde (p < 0.05) and
      increased superoxide dismutase and calcitonin gene-related peptide levels (p <
      0.05). Preconditioning also increased arterial oxygen tension and cardiac index
      compared with controls (p < 0.05) and decreased mean pulmonary artery pressure
      and pulmonary vascular resistance index (p < 0.05). Histologic findings showed
      less lung injury and a lower polymorphonuclear leukocyte count in group IP than
      in group C (p < 0.05). Group IP had fewer postoperative pulmonary complications
      and a shorter intubation time. CONCLUSIONS: Cardiac ischemic preconditioning
      improves lung preservation in patients having valve replacement. The mechanism
      may be that cardiac ischemic preconditioning reduces the accumulation of
      polymorphonuclear leukocytes in lung tissue and decreases the formation of oxygen
      free radicals.

PMID- 11235721
TI  - ATP-sensitive potassium channel openers may mimic the effects of hypoxic
      preconditioning on the coronary artery.
AB  - BACKGROUND: This study was designed to investigate the effects of the potassium
      channel opener KRN4884 in mimicking hypoxic preconditioning on coronary arteries
      and to explore the possible mechanisms. METHODS: In the organ chamber, porcine
      coronary artery rings (n = 96) were studied in 6 groups (n = 16 in each group):
      I. CONTROL: normoxia (pO2 > 200 mmHg); II. Hypoxia-reoxygenation: 60-minute
      hypoxia (pO2 < 15 mmHg) followed by 30-minute reoxygenation; III.
      Preconditioning: 5-minute hypoxia followed by 10-minute reoxygenation prior to
      hypoxia-reoxygenation; IV. KRN4884-pretreatment: KRN4884 (30 microM) was added
      into the chamber 20 minutes before hypoxia-reoxygenation; V. 5-HD-pretreatment:
      sodium 5-hydroxydecanoate (5-HD, 10 microM) was given 20 minutes prior to KRN4884
      pretreatment; and VI. GBC-pretreatment: glibenclamide (GBC, 3 microM) was added
      20 minutes prior to KRN4884-pretreatment. Concentration-contraction curves for
      U46619 (n = 8 in each group) were constructed. Concentration-relaxation curves
      for bradykinin (n = 8 in each group) related to endothelium-derived
      hyperpolarizing factor (EDHF) were established in the rings precontracted with
      U46619 (30 microM) in the presence of Nomega-nitro-L-arginine (L-NNA, 300 microM)
      and indomethacin (7 microM). RESULTS: The maximal relaxation induced by
      bradykinin was reduced in hypoxia-reoxygenation (54.6 +/- 4.3% versus 85.2 +/-
      5.7% in control, p = 0.001). This reduced relaxation was recovered in KRN4884
      pretreatment (78.9 +/- 3.7%, p = 0.014) or preconditioning (79.9 +/- 3.7%, p =
      0.009). 5-HD- but not GBC-pretreatment abolished the effect of KRN4884
      pretreatment (78.9 +/- 3.7% versus 53.5 +/- 4.7%, p = 0.009). CONCLUSIONS:
      Hypoxia-reoxygenation reduces the relaxation mediated by EDHF in the coronary
      artery. This function can be restored by either hypoxic preconditioning or the
      potassium channel opener KRN4884. The mechanism of such effect is mainly related
      to the mitochondrial ATP-sensitive K+ channels.

PMID- 11235722
TI  - Carnitine affects fatty acid metabolism after cardioplegic arrest in neonatal
      rabbit hearts.
AB  - BACKGROUND: Fatty acid (FA) metabolism and the contribution of carnitine to
      metabolism after cardioplegic arrest still remain unclear, especially in the
      neonatal heart where beta-oxidation is not a predominant source of adenosine
      triphosphate. METHODS: FA metabolism and the effects of carnitine administration
      were evaluated using a newborn (7-day-old) rabbit blood-perfused Langendorff
      model subjected to cold cardioplegic arrest. The hearts were divided into five
      groups; (1) perfused with unmodified diluted blood (n = 9), (2) subjected to 180
      minutes of cold cardioplegic arrest and reperfused with the blood (n = 9), (3)
      subjected to the same ischemia and reperfused with the blood containing 40
      microM/L (n = 9), (4) 0.5 mM/L (n = 5), and (5) 5 mM/L of carnitine (n = 5).
      During reperfusion, FA metabolism was assessed by iodine-123-labeled 15-(p
      iodophenyl)-3-(R,S)-methylpentadecanoic acid, a fatty acid. The myocardial time
      radioactivity curve was then determined and a mathematical compartment analysis
      of the external detection was used to elucidate FA metabolism in the cardiac
      myocyte. RESULTS: Cold cardioplegic arrest resulted in significantly impaired FA
      metabolism following reperfusion. Compartment analysis suggested that FA
      activation in the cytosol and beta-oxidation were impaired. Carnitine
      supplementation in groups 3 and 4 improved FA metabolism during reperfusion. In
      contrast, supplementation in group 5 had no beneficial effect on FA metabolism.
      CONCLUSIONS: These results suggest that FA metabolism is impaired after cold
      cardioplegic arrest and that carnitine supplementation may improve aerobic
      metabolism in neonates after open heart surgery.

PMID- 11235723
TI  - Mechanism underlying mechanical dysfunction in the border zone of left
      ventricular aneurysm: a finite element model study.
AB  - BACKGROUND: The global left ventricular dysfunction characteristic of left
      ventricular aneurysm is associated with muscle fiber stretching in the adjacent
      noninfarcted (border zone) region during isovolumic systole. The mechanism of
      this regional dysfunction is poorly understood. METHODS: An anteroapical
      transmural myocardial infarct was created by coronary arterial ligation in an
      adult Dorset sheep and was allowed to mature into left ventricular aneurysm for
      10 weeks. The animal was imaged subsequently using magnetic resonance imaging
      with simultaneous recording of intraventricular pressures. A realistic
      mathematical model of the three-dimensional ovine left ventricle with an
      anteroapical aneurysm was constructed from multiple short-axis and long-axis
      magnetic resonance imaging slices at the beginning of diastolic filling. RESULTS:
      Three model simulations are presented: (1) normal border zone contractility and
      normal aneurysmal material properties; (2) greatly reduced border zone
      contractility (by 50%) and normal aneurysmal material properties; and (3) greatly
      reduced border zone contractility (by 50%) and stiffened aneurysmal material
      properties (by 1000%). Only the latter two simulations were able to reproduce
      experimentally observed stretching of border zone fibers during isovolumic
      systole. CONCLUSIONS: The mechanism underlying mechanical dysfunction in the
      border zone region of left ventricular aneurysm is primarily the result of
      myocardial contractile dysfunction rather than increased wall stress in this
      region.

PMID- 11235724
TI  - Platelet PlA2 polymorphism enhances risk of neurocognitive decline after
      cardiopulmonary bypass. Multicenter Study of Perioperative Ischemia (McSPI)
      Research Group.
AB  - BACKGROUND: Neurocognitive decline, often produced by atherosclerotic plaque
      embolization, remains a frequent complication of cardiopulmonary bypass. Plaque
      fragments may initiate local thrombosis, which, in turn, aggravates the embolic
      insult. Prothrombotic genetic factors may exacerbate this process. We
      investigated whether the PlA2 polymorphism of platelet GPIIIa, a prothrombotic
      risk factor in other cardiovascular settings, is associated with early
      neurocognitive decline after cardiopulmonary bypass. METHODS: Neurocognitive
      changes were evaluated by the Mini-Mental State Examination administered
      preoperatively and on postoperative day 4 and the PlA genotype determined in 70
      patients undergoing cardiopulmonary bypass. RESULTS: Forty-nine patients were
      PlA1/A1, and 21 were PlA1/A2 or PlA2/A2. Fifty-two patients (74%) demonstrated
      post-cardiopulmonary bypass neurocognitive decline, of which 34 were PlA1/A1 and
      18 were PlA1/A2 or PlA2/A2 Multivariate analysis revealed that the PlA2 genotype
      and baseline Mini-Mental State Examination were significantly associated with
      greater neurocognitive decline (decreased Mini-Mental State Examination scores, p
      = 0.036 and 0.024, respectively). CONCLUSIONS: This study demonstrates a link
      between the PlA2 allele of platelet GPIIIa and more severe neurocognitive decline
      after cardiopulmonary bypass. Although the mechanism is unknown, it could
      represent exacerbation of platelet-dependent thrombotic processes associated with
      plaque embolism.

PMID- 11235725
TI  - Is there a relationship between cognitive dysfunction and systemic inflammatory
      response after cardiopulmonary bypass?
AB  - BACKGROUND: The systemic inflammatory reaction (SIR) is assumed to be one of the
      factors that causes cerebral dysfunction after cardiopulmonary bypass (CPB). The
      aim of the present study was to evaluate the relationship between the SIR and
      postoperative cognitive performance at 5 days and 3 months. METHODS: One hundred
      patients undergoing coronary artery bypass grafting were studied. Inflammatory
      markers and markers of coagulation and fibrinolysis were determined at several
      time points during and after the operation. Correlation analysis between maximum
      levels of the different markers and early and late performance was performed.
      RESULTS: No overall association was found between the maximum levels of the
      inflammatory markers and early and late function. CONCLUSIONS: Notwithstanding
      limitations of statistical power established markers of systemic inflammatory
      reaction showed no relationship with outcome at 5-day or 3-month follow-up in
      this subset of patients.

PMID- 11235726
TI  - Clinical implication of orbital ultrasound monitoring during selective cerebral
      perfusion.
AB  - BACKGROUND: We evaluated clinical relevance of orbital ultrasound (OUS)
      monitoring to neurological events in aortic surgery associated with selective
      cerebral perfusion (SCP). METHODS: In 24 consecutive cases, blood flow was
      monitored at central retinal artery (CRA) and retrobulbar vessels. The threshold
      perfusion pressure for detecting CRA flow in the color Doppler mode (BPt) was
      determined in individual eyes. RESULTS: The BPt ranged from 25 to 71 mm Hg.
      Events (infarction, anisocoria, delirium) occurred in 8 cases. Infarction
      occurred in all 3 cases when retrobulbar flow was severely impaired for 40
      minutes or longer, while none of the remaining 21 cases had infarction (p =
      0.0005). Among the latter cases, perfusion pressure was below BPt for longer than
      100 minutes in all 5 cases with events, and in 5 of 16 cases without events (p =
      0.0124). No significant difference was found in age, duration of cardiopulmonary
      bypass, SCP, and circulatory arrest, and duration of blood pressure below 50 mm
      Hg. CONCLUSIONS: Sustained hypoperfusion detected with OUS monitoring is related
      to an occurrence of neurological events.

PMID- 11235728
TI  - Effects of combined conventional and modified ultrafiltration in adult patients.
AB  - BACKGROUND: Modified ultrafiltration (MUF) improves hemodynamics and
      postoperative recovery in children. Ultrafiltration (UF) may have similar
      benefits in adults. The purpose of this study was to investigate the effects of
      UF in adult patients. METHODS: A total of 40 adult patients undergoing cardiac
      surgery were randomized into a study group of conventional UF during bypass +
      venovenous MUF after bypass and a control group with no UF. Perioperative
      clinical variables, cytokines, and endothelin-1 levels were compared between
      groups. RESULTS: There was no mortality in either group. The patients in the
      study group had a greater rise in hematocrit (5.7% +/- 2.4% vs 1.2% +/- 1.9%, p <
      0.001), hemoglobin (1.7 +/- 0.8 mg/mL vs 0.5 +/- 0.6 mg/mL, p < 0.0005), and
      platelet levels (27,800 +/- 29,200 vs -9,000 +/- 30,970, p < 0.001). Mean
      arterial blood pressure and CI increased after MUF (from 64.2 +/- 16.9 mm Hg to
      72.3 +/- 14.1 mm Hg, p = 0.05, and from 2.4 +/- 0.7 to 2.8 +/- 0.6, p < 0.03,
      respectively). Postoperative oxygenation was better in the study group (alveolo
      arterial PO2 tension gradient 74.6 +/- 43.9 mm Hg vs 107.2 +/- 27.8 mm Hg, p =
      0.03). Ultrafiltration reduced postoperative bleeding (522.2 +/- 233.4 mL vs 740
      +/- 198.4 mL, p < 0.003). CONCLUSIONS: A combination of conventional and modified
      UF is effective and safe in adult patients undergoing cardiac surgery.
      Ultrafiltration improved hemodynamics, hemostatic, and pulmonary functions. We
      recommend the use of combined UF in high-risk adult patients.

PMID- 11235727
TI  - Cardiac surgery with cardiopulmonary bypass in patients with type II heparin
      induced thrombocytopenia.
AB  - BACKGROUND: The use of cardiopulmonary bypass (CPB) in patients with a history of
      type II heparin-induced thrombocytopenia (HIT) may be associated with
      complications related to their anticoagulation management. METHODS: Between
      January 1997 and December 1999, among 4,850 adults patients who underwent cardiac
      surgery in our institution, 10 patients presented with preoperative type II HIT.
      In 4 patients, anticoagulation during CPB was achieved with danaparoid sodium. In
      6 other patients, heparin sodium was used after pretreatment with epoprostenol
      sodium. RESULTS: No significant change in platelet count occurred in any patient.
      No intraoperative thrombotic complication was encountered. Total postoperative
      chest drainage ranged from 250 to 1,100 ml in patients pretreated with
      epoprostenol and 1,700 to 2,470 ml in patients who received danaparoid sodium
      during CPB (p < 0.05, Mann-Whitney U test). CONCLUSIONS: During CPB, inhibition
      of platelet aggregation by prostacyclin may be a safe anticoagulation approach in
      patients with type II HIT.

PMID- 11235729
TI  - Cervical and thoracic components of multiorgan lymphangiomatosis managed
      surgically.
AB  - We report a patient who presented for management of suspected metastatic
      carcinoma of unknown origin. The lesions proved to be lymphangiomatosis involving
      multiple organ systems. Surgical management of the thoracic and cervical
      components of this rare condition is described.

PMID- 11235730
TI  - Recurrence of pulmonary mucinous cystic tumor of borderline malignancy.
AB  - Cystic mucinous tumors of the lung are recently described neoplasms whose
      histology is different from most lung adenocarcinomas, and represent a spectrum
      of malignant potential. Little is known of the behavior of the more malignant
      subtype. We present a cystic mucinous tumor of borderline malignancy that
      recurred locally following initial limited resection, and was treated with
      lobectomy.

PMID- 11235731
TI  - Inflammatory endobronchial stenosis.
AB  - We encountered a 71-year-old woman with inoperable bronchial stenosis of the
      right main bronchus, which was caused by inflammatory granulation infected with
      Pseudomonas aeruginosa in posttuberculous bronchiectasis. Two months after
      placement of self-expanding nitinol stents, fiberoptic bronchoscopic examination
      to investigate hemosputum revealed endobronchial granuloma formation.
      Endobronchial granulation has disappeared with long-term oral administration of
      tranilast.

PMID- 11235732
TI  - Middle mediastinal parathyroid: diagnosis and surgical approach.
AB  - We report two cases of middle mediastinal parathyroid ectopia associated with
      chronic renal disease. In both patients the diagnosis was delayed and prolonged
      due to the unusual location of the ectopic parathyroid tissue. The surgical
      approach was in error in 1 patient and corrected during the second procedure. We
      describe the surgical technique for exposing and excising parathyroid tissue from
      this area.

PMID- 11235733
TI  - Postpneumonectomy syndrome after left pneumonectomy.
AB  - Postpneumonectomy syndrome, a late complication of pneumonectomy, is secondary to
      shift of the mediastinum and remaining lung toward the pneumonectomy side,
      leading to tracheobronchial compression between the vertebral body and the aorta
      or pulmonary artery. Obstructive airway symptoms are usually due to
      tracheobronchial tree compression, however, secondary airway malacia may develop.
      We report herein a case of postpneumonectomy syndrome with secondary
      bronchomalacia after left pneumonectomy in a patient with normal mediastinal
      vascular anatomy.

PMID- 11235734
TI  - Drug-induced methemoglobinemia during thoracoscopic lung biopsy.
AB  - Acquired methemoglobinemia occurs rarely in clinical practice. We present a case
      of a 57-year-old man who developed severe drug-induced methemoglobinemia after
      exposure to benzocaine spray and lidocaine jelly during intubation for an
      elective thoracoscopic lung biopsy. Information regarding the classifications,
      pathophysiology, diagnosis, and treatment of this entity is reviewed.

PMID- 11235735
TI  - Stented elephant trunk method for multiple thoracic aneurysms.
AB  - Stent-grafting and open graft replacement was introduced to reduce the
      complications of suture anastomosis in the descending aorta. We applied this
      technique in the treatment of a patient with multiple thoracic aneurysms. The
      elephant trunk procedure was used for thromboexclusion. A single branched graft
      was placed easily without twisting. In patients with aneurysms at both the
      proximal and distal thoracic aorta, combined stent-grafting and open graft
      replacement is an excellent approach.

PMID- 11235736
TI  - Giant pseudoaneurysm of the right sinus of Valsalva.
AB  - A pseudoaneurysm of the sinus of Valsalva is a very rare cardiac abnormality. We
      report a surgical case of the pseudoaneurysm of the right sinus of Valsalva in a
      77-year- old woman. The histopathological examination of the resected aneurysmal
      wall revealed that it was a pseudoaneurysm without any specific inflammatory
      changes. Although we cannot identify the clear cause of the formation of the
      pseudoaneurysm, we believe it may have been a type of spontaneous rupture of the
      sinus of Valsalva.

PMID- 11235737
TI  - Pulmonary vein orifice isolation for elimination of chronic atrial fibrillation.
AB  - We present a 61-year-old woman with chronic atrial fibrillation (AF) associated
      with mitral valve disease. Chronic AF was successfully treated by simple
      isolation of pulmonary vein orifices concomitant with mitral valve replacemen

PMID- 11235738
TI  - Late-onset dysphagia lusoria.
AB  - Symptomatic vascular rings are uncommon in adults. We report a case of dysphagia
      in a 48-year-old woman from a right-sided aortic arch with aberrant left
      subclavian artery and left-sided ligamentum arteriosum. Through a left
      posterolateral thoracotomy, the ligamentum was divided, relieving the patient's
      dysphagia. Twenty-three cases of adult-onset dysphagia lusoria attributable to
      this anatomy have been reported. We recommend a left thoracotomy with division of
      the ligamentum as treatment.

PMID- 11235739
TI  - Cardiac pheochromocytoma.
AB  - Primary pheochromocytomas of the heart are extremely uncommon. In this report, we
      present the case of a patient with primary cardiac pheochromocytoma arising from
      the interatrial septum. Metaiodobenzylguanidine-scintigraphy was negative and
      diagnosis was confirmed by a positive octreotide scintiscan. The tumor was
      removed successfully using cardiopulmonary bypass.

PMID- 11235741
TI  - Successful staged-Fontan operation in a patient with ectopia cordis.
AB  - Ectopia cordis is a very rare and often fatal disease. We report a successful
      surgery case of thoracoabdominal ectopia cordis with univentricular heart. This
      patient underwent a three-stage Fontan procedure, a right-modified Blalock
      Taussig shunt at the age of 1 month, bidirectional Glenn shunt and pulmonary
      arterioplasty at 2 years 8 months, and finally a total cavopulmonary connection
      at 4 years. This patient was discharged from the hospital in good condition and
      has been doing well since. Thus, ectopia cordis is not a contraindication for a
      Fontan operation.

PMID- 11235740
TI  - Interventional and surgical management of aortic stenosis and coarctation.
AB  - Two patients, aged 42 and 44 years old, presented with the combination of aortic
      valve stenosis and coarctation. To avoid potential problems associated with one
      stage repair, both patients underwent successful endovascular stent implantation
      for coarctation followed within 2 weeks by aortic valve replacement using
      pulmonary autografts (Ross operation). Spiral thoracic computed tomographic scans
      were performed within 1 week of stent implantation to ensure the absence of
      aneurysm formation related to the stent before cardiopulmonary bypass.

PMID- 11235742
TI  - Infant partial left ventriculectomy for failure to wean from cardiopulmonary
      bypass.
AB  - Following aortic reimplantation of anomalous left coronary artery from the
      pulmonary artery in a 6-month-old infant, the heart failed to wean after
      prolonged supportive cardiopulmonary bypass and maximal inotropic support. We
      performed partial left ventriculectomy (Batista procedure) that halved left
      atrial pressure and enabled discontinuation of bypass. Postoperative recovery was
      then uneventful.

PMID- 11235743
TI  - Left atrial aneurysm.
AB  - Aneurysms of the left atrium are rare abnormalities. They can be congenital or
      acquired. Whereas a true congenital aneurysm presents as isolated pathology,
      inflammatory or degenerative processes involving the endocardium are associated
      with the acquired type. The clinical records of 2 patients with the diagnosis of
      left atrial aneurysm were reviewed, along with the surgical strategies, current
      literature, and patient outcomes. Because of the risk of life-threatening
      complications, surgery is recommended even in asymptomatic cases. Resection and
      mitral valvuloplasty should be the treatment of choice.

PMID- 11235744
TI  - Congenital pulmonary vein stenosis associated with cor triatriatum.
AB  - We report an 11-year-old boy who underwent surgical correction for stenosis of
      the right and left lower pulmonary veins at their junction with the left atrium
      and associated cor triatriatum. The embryology and therapeutic approaches to
      congenital pulmonary veins stenosis are discussed.

PMID- 11235745
TI  - Modified repair of mixed total anomalous pulmonary venous connection.
AB  - Mixed total anomalous pulmonary venous connection (TAPVC) is a rare condition,
      accounting for only 5% of diagnosed TAPVC. It is associated with a poor prognosis
      unless surgically corrected by connecting the pulmonary venous sinus to the left
      atrium and optionally dividing the abnormal connection to the systemic venous
      system. We report a modified technique of complete intracardiac repair of mixed
      supracardiac and cardiac TAPVC in a 3-year-old child without pulmonary venous
      sinus-to-left atrium anastomosis.

PMID- 11235746
TI  - Cavopulmonary connection after repair of pulmonary vein stenoses.
AB  - We report a case of heterotaxia with single-ventricle physiology undergoing
      successively pulmonary artery banding (PAB) at 8 months of age, repair of
      pulmonary vein (PV) stenoses at 15 months of age, and a fenestrated total
      cavopulmonary connection (TCPC) combined with repair of a regurgitant common
      atrioventricular (AV) valve and a Damus-Stansel operation for a restrictive
      subaortic ventricle at 5 years of age, followed by percutaneous closure of the
      fenestration. The child is now 10 years old and is, to the best of our knowledge,
      the only reported long-term survivor of a Fontan type procedure done after repair
      of PV stenoses.

PMID- 11235747
TI  - Endovascular stent graft treatment of a pulmonary artery pseudoaneurysm.
AB  - A 5-year-old girl with pulmonary atresia, ventricular septal defect, hypoplastic
      pulmonary arteries, and multiple pulmonary artery reconstructive procedures
      presented with an enlarging pulmonary artery pseudoaneurysm. A previous attempt
      to occlude the aneurysm was unsuccessful and the aneurysm continued to enlarge.
      We describe the percutaneous placement of an endovascular stent graft to occlude
      the aneurysm. This novel use of a covered graft effectively treated a potentially
      lethal problem without reoperative thoracotomy or sternotomy.

PMID- 11235748
TI  - A vascular ring: right aortic arch and descending aorta with left ductus
      arteriosus.
AB  - A case is presented of vascular ring caused by right aortic arch with mirror
      image branching and left ductus arteriosus. In this case, the descending aorta
      was located right of the tracheoesophagus and the left ductus arteriosus
      connected to the descending aorta far below the arch, producing compression of
      the esophagus only. Through median sternotomy, the ligation and division of the
      ductus was performed with concomitant repair of ventricular septal defect.

PMID- 11235749
TI  - Cardiac denervation after transmyocardial laser.

PMID- 11235750
TI  - Resection of right atrial tumor thrombi without circulatory arrest.
AB  - Resectable retroperitoneal tumors with right atrial tumor thrombus extension have
      been excised previously using cardiopulmonary bypass and deep hypothermic
      circulatory arrest. We have used a technique involving clamping of the descending
      aorta with avoidance of deep hypothermic circulatory arrest in 6 patients. The
      approach provided a virtually bloodless field and allowed complete resection to
      be performed with low morbidity.

PMID- 11235751
TI  - Use of ECMO without the oxygenator to provide ventricular support after Norwood
      Stage I procedures.
AB  - Extracorporeal membrane oxygenation (ECMO) has been found effective in supporting
      infants with severe cardiac dysfunction following open heart surgery. Centers
      using this mode of support can also, in instances of single ventricle morphology,
      consider the option of eliminating the oxygenator from the standard ECMO set-up
      and thereby provide roller pump ventricular assist. In these cases, the infant's
      own lungs can provide excellent oxygenation simply by leaving the aortopulmonary
      shunt open. Since ventricular support ensures maintenance of normal cardiac
      output, manipulation of pulmonary versus systemic flows is not necessary. This
      configuration retains the safety features of the ECMO system and is easily
      staffed by the ECMO support personnel. There may be several benefits to employing
      this type of management.

PMID- 11235752
TI  - Pericardial reinforcement after partial atrial resection in idiopathic
      enlargement of the right atrium.
AB  - A 2-year-old boy in whom idiopathic enlargement of the right atrium was diagnosed
      in utero by fetal echocardiography underwent surgical intervention because of
      progression of right atrial dilatation. During operation, the lateral right
      atrial wall was externally reinforced after partial resection by approximating
      and fixing the neighboring autologous pericardium around the external
      circumference of the right atrium. This technique is a useful means of preventing
      recurrence of dilatation in histologically abnormal right atrial tissue that
      predisposes the patient to possible reintervention.

PMID- 11235753
TI  - Endoscopic vein harvesting with the aid of carbon dioxide insufflation.
AB  - Endoscopic harvesting of the long saphenous vein has been introduced to decrease
      the morbidity of obtaining venous conduit for coronary artery bypass grafting.
      Herein is described an endoscopic method using carbon dioxide insufflation into
      the tissues around the vein. This has several advantages; improved vision, no
      physical retraction required, easier development of tissue planes, and improved
      hemostasis.

PMID- 11235754
TI  - Technique for blood conservation in ABIOMED BVS 5000 ventricular assist device
      exchange.
AB  - We describe a technique for blood conservation when ABIOMED BVS 5000 blood pumps
      require exchange because of thrombus formation in the blood pumps. The technique
      is simple in concept but requires careful planning and coordination between
      surgeon and perfusionist.

PMID- 11235755
TI  - Aprotinin and the systemic inflammatory response after cardiopulmonary bypass.
AB  - Cardiopulmonary bypass is associated with a systemic inflammatory response, a
      spectrum of pathophysiologic changes ranging from mild organ dysfunction to
      multisystem organ failure. Complications include coagulation disorders (bleeding
      diathesis, hyperfibrinolysis) from platelet defects and plasmin activation, as
      well as pulmonary dysfunction from neutrophil sequestration and degranulation.
      Diverse injuries are a consequence of multiple inflammatory mediators
      (complement, kinins, kallikrein, cytokines). Both plasmin and kallikrein amplify
      the inflammatory response by activating components of the contact activation
      system. The full-Hammersmith (high dose) of aprotinin, a serine protease
      inhibitor approved for reducing blood loss and transfusion requirements in
      cardiopulmonary bypass, inhibits kallikrein and plasmin, resulting in suppression
      of multiple systems involved in the inflammatory response. Specifically,
      inhibition of factor XII, bradykinin, C5a, neutrophil integrin expression,
      elastase activity, and airway nitric oxide production are observed. Clinical
      correlates include reduced capillary leak, preserved systemic vascular resistance
      and blood pressure, and improved myocardial recovery following ischemia. Overall,
      evidence indicates that aprotinin attenuates the systemic inflammatory response
      associated with cardiopulmonary bypass.

PMID- 11235756
TI  - As originally published in 1994: Development of tolerance to experimental cardiac
      allograft in utero. Updated in 2001.

PMID- 11235757
TI  - The surgeon and the follow-up clinic.

PMID- 11235758
TI  - Reconstruction of the pulmonary artery with a pericardial tubular graft.

PMID- 11235759
TI  - Types of esophageal repair after primary aortoesophageal fistula resection.

PMID- 11235760
TI  - Control of bleeding from fragile sternum with a resorbable hemostyptic.

PMID- 11235761
TI  - Steel strut fracture after pectus excavatum operation: a technical problem?

PMID- 11235762
TI  - Leaflet escape in a Tekna valve in aortic position.

PMID- 11235763
TI  - Plica transversae aortae--fold of Rindfleisch.

PMID- 11235764
TI  - Repeat coronary artery bypass via left thoracotomy.

PMID- 11235765
TI  - Adjusting length of aortocoronary saphenous vein bypass grafts.

PMID- 11235766
TI  - Contributions of women to general thoracic surgery.

PMID- 11235767
TI  - Collective contributions of women to cardiothoracic surgery: a perspective
      review.
AB  - BACKGROUND: Of 5,812 persons boarded by the American Board of Thoracic Surgery
      (ABTS), 99 (< 2%) are women. This study was designed to collect and report the
      contributions made by these women in the specialty of cardiothoracic surgery.
      METHODS: Identification of ABTS board-certified women was obtained from the ABTS.
      Compilation of data was accomplished through membership databases, medical
      licensing boards, thoracic surgery residency programs, and residency program
      attending surgeons. Data were substantiated through hospital medical staff
      offices, local practitioners, and personal telephone calls. Curricula vitae were
      requested; practice types (adult, pediatric, cardiac, general thoracic, or
      transplantation) were established. Data were collated, extrapolated, and tallied.
      Trends over time were analyzed by logistic regression analyses. RESULTS:
      Currently, 84 women are actively practicing: 44 have academic appointments and 40
      are in private practice. Of the remaining 15 women, 4 are deceased; 4 are
      retired; 5 are in other professional fields; and 2 are in an unknown practice
      setting. Accumulated data confirmed that women surgeons are practicing in every
      type and subgroup of cardiothoracic surgery (adult, pediatric, cardiac, general
      thoracic, transplantation, and combinations of these). Collectively, they have
      published 2,292 articles and book chapters. Manuscripts directly related to
      cardiac topics number 1,220. Women in cardiothoracic surgical research have been
      awarded $31.9 million in grant funds. Two trends over time were identified.
      First, the distribution of practice setting (academic or private) was stable
      compared with year of board certification. Secondly, a statistically significant
      rise in the annual percentage of board-certified persons who are women (p <
      0.0001) has been established. CONCLUSIONS: The percent of ABTS board-certified
      women surgeons has increased; more than 50% have academic appointments; and a
      stable trend for women to choose academic cardiothoracic surgery exists.

PMID- 11235768
TI  - Training women surgeons and their academic advancement.
AB  - The responsibility for those of us involved in residency training programs is to
      foster the development of future leaders in thoracic surgery. Although the actual
      training of female surgeons is no different than training male surgeons, academic
      advancement after training can be more difficult for women due to a variety of
      reasons. The education and training of female surgeons has its origin in
      admission to medical school followed by recruitment into a residency program.
      Following completion of a residency program, the retainment of women and men
      faculty should be the goal of departments and divisions of thoracic surgery.
      Specific recommendations are made for retainment of faculty. In addition to
      academic promotion and financial reward, creating the proper environment is an
      important consideration to allow women the chance to succeed in medicine. This
      report addresses the training aspects involved in the thoracic residency program
      and the state of professional academic advancement at the Johns Hopkins
      University School of Medicine.

PMID- 11235769
TI  - Women in thoracic surgery and the Thoracic Surgery Foundation for Research and
      Education.

PMID- 11235770
TI  - The evolution of women as physicians and surgeons.
AB  - Women have played an active role as physicians and surgeons from earliest
      history. In the United States, medical education for women began in 1847 and
      flourished as medical schools proliferated to meet the growing population demand.
      The Flexner Report in 1910 resulted in about half the medical schools in the U.S.
      closing; many of them had admitted women. The number of women medical students
      increased beginning in the 1970s, until now, 43% of medical school graduates are
      women. The number of women residents has increased concomitantly from 22% in 1980
      to 36% in 1997. Women residents in surgical training programs lag behind.
      Thoracic surgery has the lowest percent of women residents, at 5%. Unless an
      attempt is made to actively recruit women, thoracic surgery training programs are
      in danger of drawing from an increasingly smaller portion of medical school
      graduates.

PMID- 11235771
TI  - Our contributions: scholarship revisited.

PMID- 11235772
TI  - Nina Starr Braunwald: some reflections on the first woman heart surgeon.

PMID- 11235773
TI  - "The XX files": demographics of women cardiothoracic surgeons.

PMID- 11235774
TI  - Can practitioners use the WHO definition for osteoporosis?

PMID- 11235776
TI  - Tenology: a new frontier.
AB  - Tendons were long given little recognition by rheumatologists. Yet, their complex
      structure and distinctive functional characteristics have been demonstrated by an
      abundance of histological, biochemical, and biomechanical studies: clearly,
      tendons are not inert cords linking muscles to bones. The current wave of
      popularity of sporting activities has brought with it an epidemic of disorders of
      the tendons, thus focusing attention on these structures. At the same time,
      modern imaging techniques (particularly magnetic resonance imaging) have allowed
      clinicians to improve their knowledge of and classification schemes fortendon
      disorders. Several risk factors, including technical factors, have been
      identified, so that preventive treatment is now as important as curative
      treatment. Culture systems for tenocytes (the specialized fibroblasts found in
      tendons) are now available and have been used to develop experimental models,
      paving the way for significant advances in tendon repair techniques.

PMID- 11235775
TI  - Do the HLA-DQ and DP genes play a role in rheumatoid arthritis?
AB  - Whereas the DRB1 alleles have well-established associations with rheumatoid
      arthritis (RA), the DQ and DP alleles are of more controversial relevance to RA.
      Early studies of the DQB1 genes in RA determined the frequencies of the two
      DQB1*03 subtypes that are in linkage disequilibrium with DR4, DQB1*0301 (DQw7)
      and *0302 (DQw8). Their results are conflicting and difficult to interpret
      because molecular biology techniques for determining DR4 specificity polymorphism
      were not available at the time. None of the more recent studies found compelling
      evidence that the DQB1 alleles influenced the susceptibility to RA. A few studies
      suggest that the DQ alleles may influence the clinical or biological expression
      of the disease, perhaps through a complementary effect of the DRB1 and DQB1
      alleles. DR-DQ complementarity has been demonstrated in the DQ8 transgenic mouse
      model, although this is not necessarily relevant to the human disease. The role
      of DPB1 remains hypothetical but may involve an influence of some alleles in
      relatively mild forms of RA. The DQB1 and DPB1 alleles are in strong linkage
      disequilibrium with the DRB1 alleles, making the elucidation of their independent
      effects a challenging task. Studies are needed to determine whether these linkage
      disequilibriums can influence the development of autoimmune diseases.

PMID- 11235777
TI  - Gonadal dysgenesis and bone metabolism.
AB  - Gonadal dysgenesis is defined as congenital hypogonadism related to abnormalities
      of the sex chromosomes. Because sex steroids play a central role in the
      acquisition and maintenance of bone mass, studies have been done to investigate
      bone status in patients with gonadal dysgenesis, particularly Turner's syndrome
      and Klinefelter's syndrome, which are the two most common types. The severe
      estrogen deficiency characteristic of Turner's syndrome (44, X0) is associated
      with a significant bone mass decrease ascribable to increased bone turnover, as
      shown by histological studies and assays of bone turnover markers. Estrogen
      therapy is followed by a significant bone mass gain and a return to normal of
      bone turnover markers, suggesting that it is the estrogen deficiency rather than
      the chromosomal abnormality that causes the bone mass deficiency, although
      abnormalities in the renal metabolism of vitamin D have been reported. Combined
      therapy with estrogens and growth hormone seems beneficial during the prepubertal
      period. In Klinefelter's syndrome (47XXY), serum testosterone levels are at the
      lower end of the normal range and dihydrotestosterone levels are low.
      Histological studies show depressed osteoblast function and a decrease in 5-alpha
      reductase activity responsible for partial tissue resistance to androgens. Assays
      of bone turnover markers show evidence of increased bone turnover. The bone
      deficiency is most marked at the femoral neck and seems correlated with serum
      testosterone and estradiol levels. Androgen therapy has favorable effects on the
      bone only if it is started before puberty. Recent data suggest that estrogens may
      contribute to the development of demineralization in KS and that bisphosphonate
      therapy may be beneficial.

PMID- 11235778
TI  - Prospective X-ray densitometry and ultrasonography study of the hand bones of
      patients with rheumatoid arthritis of recent onset.
AB  - OBJECTIVE: Bone demineralization observed in early rheumatoid arthritis is not
      easily measured. To measure bone loss and to discriminate between rheumatoid
      arthritis and other rheumatic diseases, we used two methods: dual-energy X-ray
      absorptiometry and ultrasonography. METHODS: From a population-based recruitment,
      32 patients with early peripheral polyarthritis (median disease duration: 4
      months) were studied. Clinical, laboratory, functional, hand-bone assessments
      were made at the entry an at months 6 and 12. Bone X-ray densitometry
      measurements were made on 16 areas of the hand. Speed of sound was measured
      across the proximal phalanges of the four fingers. X-rays of both hands were
      scored according to the modified Sharp's score. At 12 months, patients were
      classified as rheumatoid arthritis (N = 15; 9 F) or as other rheumatic diseases.
      RESULTS: We found: 1) significantly decreased bone mineral density (BMD) of the
      whole hand, in the rheumatoid arthritis group versus the other rheumatic diseases
      group, at 6 and 12 months (P < 0.05); 2) no significant decrease of bone mineral
      density (BMD) in other areas in the rheumatoid arthritis group; 3) no significant
      change of ultrasounds in either group; and 4) no significant correlation between
      the decrease of BMD in the rheumatoid arthritis group and clinical, biological or
      radiologic parameters, except for IFNgamma, whose production in whole blood cell
      culture was lower at entry in the rheumatoid arthritis group. CONCLUSION: DEXA
      bone assessment in rheumatoid arthritis was able t detect bone loss in the whole
      hand at 6 months.

PMID- 11235779
TI  - Interleukin 10: a new therapeutic target in systemic lupus erythematosus?

PMID- 11235780
TI  - Forceful sacrococcygeal injections in the treatment of postdiscectomy sciatica. A
      controlled study versus glucocorticoid injections.
AB  - The role of epidural fibrosis in postoperative sciatica is unclear. Few
      therapeutic trials have been published. We evaluated the mechanical effects of
      forceful saline injections through the sacrococcygeal hiatus comparatively with
      glucocorticoid injections. PATIENTS AND METHODS: Forty-seven patients with
      postdiscectomy sciatica but no evidence of compression by computed tomography or
      magnetic resonance imaging were included in a multicenter, randomized,
      controlled, parallel-group study comparing forceful injections of saline (20 ml)
      with or without prednisolone acetate (125 mg) to epidural prednisolone acetate
      (125 mg) alone. Each of the three treatments was given once a month for three
      consecutive months. Outcome measures were pain severity on a visual analog scale
      (VAS) and the scores on the Dallas algofunctional self-questionnaire on day 0,
      day 60, and day 120. Analysis of variance for repeated measures and Student's t
      test for paired series were used to evaluate the data. RESULTS: Forty-seven
      patients were evaluated. The VAS score improved significantly between day 0 and
      day 30 in the glucocorticoid group as compared to the forceful injection group (P
      = 0.01). No other significant differences were found across the groups. The VAS
      score improved steadily in the forceful injection group, producing a nearly
      significant difference on day 120 as compared to baseline (P = 0.08). CONCLUSION:
      Forceful epidural injections produced a non-significant improvement in
      postdiscectomy sciatica four months after surgery. Epidural glucocorticoids used
      alone induced short-lived pain relief.

PMID- 11235781
TI  - Factors predicting radical treatment after in-hospital conservative management of
      disk-related sciatica.
AB  - OBJECTIVE: To determine predictive factors for radical treatment (nucleolysis or
      surgery) after in-hospital conservative management of low back pain with sciatica
      (LBPS). PATIENTS AND METHODS: A standardized form was used to collect data on 134
      patients admitted for conservative treatment of LBPS. Subsequent radical
      procedures were recorded 11 to 24 months after discharge. RESULTS: Forty-seven
      patients required radical treatment after discharge. Significant risk factors for
      radical treatment in the univariate analysis were taller stature, use of a lumbar
      support, more preadmission epidural injections, a positive straight leg-raising
      test, and a disk herniation diameter of at least 50% of the spinal canal
      diameter. Protective factors were onset within the month preceding admission and
      normal range of motion of the lumbar spine. In the multivariate analysis, symptom
      duration longer than one month, use of a lumbar support prior to admission, and a
      positive straight leg-raising test were associated with radical treatment. A
      positive straight leg-raising test was the only significant clinical risk factor
      in the subset of patients investigated by computed tomography (CT). When CT
      findings were added to the model, only size of the herniation was significant.
      CONCLUSION: Sixty-five percent of patients admitted for conservative treatment of
      LBPS do not receive radical treatment during a mean follow-up of 18 months.
      Several factors are associated with the likelihood of radical treatment.

PMID- 11235782
TI  - An evaluation of the association between fibromyalgia and repetitive strain
      injuries in metalworkers of an industry in Guarulhos, Brazil.
AB  - Repetitive strain injuries are a common diagnostic label for musculoskeletal pain
      occurring at the workplace. Although many individuals present with diffuse pain,
      the diagnosis of fibromyalgia in this setting is rare. Our objective was to
      establish the point prevalence of the fibromyalgia syndrome in a population of
      assembly line workers in Sao Paulo, Brazil. METHODS: Thirty-four workers with
      repetitive strain injury diagnoses were studied and compared with 49 workers,
      paired by age, sex, and labor function. All individuals were studied by a
      comprehensive clinical protocol. Diagnosis of fibromyalgia syndrome was
      established when the 1990 American College of Rheumatology criteria for this
      syndrome were met. RESULTS: Among the 34 workers with the diagnosis of repetitive
      strain injuries, 58.8% fulfilled the American College of Rheumatology criteria
      for fibromyalgia syndrome, while only 10.4% of the controls met the same
      criteria. CONCLUSIONS: Fibromyalgia syndrome was largely involved in the symptoms
      of patients with repetitive strain injuries, as opposed to coworkers with non
      repetitive strain injuries. So, instead of the repetitive strain injuries label,
      many of these cases should be called fibromyalgic patients.

PMID- 11235783
TI  - Advances in osteoarticular ultrasonography.

PMID- 11235784
TI  - Interindividual variations in beliefs about the placebo effect: a study in 300
      rheumatology inpatients and 100 nurses.
AB  - PATIENTS AND METHODS: Three hundred patients admitted to a rheumatology
      department (mean age, 49.2+/-15.5 years) and 100 nurses working in the same
      teaching hospital (mean age, 36+/-8.6 years) completed a questionnaire on the
      placebo effect in the treatment of pain. RESULTS: The patients believed that the
      percentages of subjects who responded occasionally or consistently to a placebo
      were 32% (+/- 22%) and 21% (+/- 17%), respectively. The figures given by the
      nurses were only slightly higher: 42% (+/- 23%) and 23% (+/- 17%), respectively.
      Only 27% of the patients and 58% of the nurses knew that pain could resolve
      completely under placebo therapy. The mean percentage improvement induced by
      placebo therapy as compared to the study analgesic was estimated at 21% (+/- 17%)
      by the patients and 30% (+/- 18%) by the nurses. Only 23% of patients and 24% of
      nurses knew about nocebo effects. CONCLUSION: These data suggest that during
      double-blind placebo-controlled trials three-quarters of the placebo arm patients
      who experience a marked improvement or a nocebo effect may believe they received
      the active drug. This is likely to reduce the difference between the placebo and
      active drug groups. Furthermore, most patients and nurses have a negative
      perception of placebo therapy. It may be useful to include a brief description of
      placebo and nocebo effects into the patient's information and informed consent
      documents used in double-blind placebo-controlled trials.

PMID- 11235785
TI  - Postpartal sacral fracture without osteoporosis.
AB  - Stress fractures of the sacrum during pregnancy or the postpartum seem uncommon.
      We report a new case of nontrauma-related postpartal sacral fracture. Only four
      similar cases have been reported to date. The patient was 36 years of age and her
      fracture was diagnosed four weeks after her first delivery. Vitamin D levels were
      low, but there was no osteomalacia. Other standard laboratory tests were normal,
      as were absorptiometry measurements at the lumbar spine and femur.
      Rheumatologists should consider sacral fracture in pregnant or nursing patients
      with buttock pain. Magnetic resonance imaging is the diagnostic investigation of
      choice.

PMID- 11235786
TI  - Iliac bone defects revealing systemic sarcoidosis.
AB  - Bone lesions are fairly uncommon in sarcoidosis (5 to 10% of cases). We report
      the case of a 40-year-old man in whom sarcoidosis of the lungs and bones was
      revealed by excruciating buttock and sacral pain. Computed tomography showed
      multiple punched-out defects in the left iliac bone. No similar cases have been
      reported in the literature.

PMID- 11235787
TI  - A shock associated with adult-onset Still's disease.
AB  - Only two cases of adult-onset Still's disease associated with shock have been
      previously described. We report a case of shock in a man with adult-onset Still's
      disease and discuss the relationship between the two processes by assessing tumor
      necrosis factor-alpha, procalcitonin and interleukin-6 concentrations.

PMID- 11235788
TI  - Iliac vein thrombosis complicating SAPHO syndrome: MRI and histologic features of
      soft tissue lesions.
AB  - Subclavian and superior vena cava obstruction complicating SAPHO (Synovitis,
      Acne, Pustulosis, Hyperostosis, Osteitis) syndrome has been described. We report
      the first case to our knowledge of iliac vein thrombosis complicating lumbar
      vertebral osteitis due to SAPHO syndrome. Lumbar MRI demonstrated a large tissue
      mass anterior to the involved vertebras and surrounding the right iliac vein.
      Histology of the mass showed aseptic inflammation.

PMID- 11235789
TI  - Hoffmann's syndrome in hypothyroid myopathy. Report of a case in an African.

PMID- 11235790
TI  - Septic arthritis due to Kingella kingae in an adult.

PMID- 11235791
TI  - Relationships between seat properties and human subject kinematics in rear impact
      tests.
AB  - The mitigation of whiplash associated disorders (WAD) has received increased
      priority in the last 10 years. Although the exact mechanism(s) for WAD causation
      have not been established, several have been proposed and it is likely the
      mechanism(s) are associated with the kinematics of the head relative to the
      torso. It follows that automotive seat designs that address reductions in certain
      head-torso kinematics may lead to a reduction in WAD potential. Seat properties
      that may have an effect on head-neck kinematics include geometry, stiffness and
      energy absorption. This study evaluated the performance of five seats with
      varying properties, including the new Volvo 'WHIPS' seat. Seat properties such as
      geometry relative to the occupant's head, dynamic and static stiffness, and
      energy absorption were determined via component testing. A new prototype dynamic
      seat test, which used a pendulum and seat back pan, was evaluated. Human subject
      impact tests were conducted using three occupants in rear impacts with velocity
      changes of 4 and 8 km/h. Potentially relevant occupant kinematic parameters were
      identified, and then correlated with seat properties in an attempt to determine
      any relative influence of seat properties on potential WAD mechanisms. Two higher
      velocity human subject tests using the Volvo Whiplash Injury Protection System
      (WHIPS) seat were also conducted. Vertical and horizontal head to head restraint
      distances were found to be most influential on occupant head-neck kinematics.
      Horizontal and vertical head to head restraint offsets were significantly
      correlated with rearward translational motion of the head center of gravity
      relative to the upper torso across all occupants. Rearward offset was also
      significantly correlated with rearward rotation of the head relative to upper
      torso, while vertical offset was significantly correlated with head acceleration
      relative to the upper torso during the flexion phase of the impact. Seat
      constitutive properties such as stiffness and energy absorption were not
      significantly correlated with occupant head-neck kinematics. The new dynamic seat
      test posed problems in data interpretation, and suggestions for improvement are
      made. The Volvo 'WHIPS' seat proved to be very effective in reducing many
      potential WAD associated head-neck kinematics. The two increased severity impacts
      activated the additional protective energy absorption elements in the seat, and
      no injuries were sustained by the occupants.

PMID- 11235792
TI  - Experimental analysis of a new flexible neck model for low-speed rear-end
      collisions.
AB  - Whiplash injuries occur frequently in rear-end automobile accidents even at low
      speed. The hybrid III dummy has been used for various tests in order to
      investigate the mechanism of whiplash injuries. However, since this dummy neck is
      too rigid for low-speed collisions, we developed a new flexible neck model for
      low-speed rear-end collisions. Each component of this new flexible neck model is
      made of polymers with material properties close to those of the human body. Sled
      tests were conducted to measure the displacements of cervical vertebrae of the
      new flexible neck model at 11 km/h. The figures of s-shape and shear displacement
      in the plane of the intervertebral disks were observed, and it was recognized
      that shear displacement resulted from the inconsistency of motion between the
      head and neck. The regions of shear displacement agreed well with the statistics
      of the critical regions where whiplash injuries have frequently occurred. It is
      assumed that shear displacement is one of the causes of the mechanism of whiplash
      injuries.

PMID- 11235793
TI  - Developing measures of fatigue using an alcohol comparison to validate the
      effects of fatigue on performance.
AB  - The effects of 28 h of sleep deprivation were compared with varying doses of
      alcohol up to 0.1% blood alcohol concentration (BAC) in the same subjects. The
      study was conducted in the laboratory. Twenty long-haul truck drivers and 19
      people not employed as professional drivers acted as subjects. Tests were
      selected that were likely to be affected by fatigue, including simple reaction
      time, unstable tracking, dual task, Mackworth clock vigilance test, symbol digit
      coding, visual search, sequential spatial memory and logical reasoning. While
      performance effects were seen due to alcohol for all tests, sleep deprivation
      affected performance on most tests, but had no effect on performance on the
      visual search and logical reasoning tests. Some tests showed evidence of a
      circadian rhythm effect on performance, in particular, simple reaction time, dual
      task, Mackworth clock vigilance, and symbol digit coding, but only for response
      speed and not response accuracy. Drivers were slower but more accurate than
      controls on the symbol digit test, suggesting that they took a more conservative
      approach to performance of this test. This study demonstrated which tests are
      most sensitive to sleep deprivation and fatigue. The study therefore has
      established a set of tests that can be used in evaluations of fatigue and fatigue
      countermeasures.

PMID- 11235794
TI  - Area-wide urban traffic calming schemes: a meta-analysis of safety effects.
AB  - This paper presents a meta-analysis of 33 studies that have evaluated the effects
      on road safety of area-wide urban traffic calming schemes. Area-wide urban
      traffic calming schemes are typically implemented in residential areas in towns
      in order to reduce the environmental and safety problems caused by road traffic.
      A hierarchical road system is established and through traffic is removed from
      residential streets by means of, for example, street closures or one-way systems.
      Speed reducing devices are often installed in residential streets. Main roads are
      improved in order to carry a larger traffic volume without additional delays or
      more accidents. The meta-analysis shows that area-wide urban traffic calming
      schemes on the average reduce the number of injury accidents by about 15%. The
      largest reduction in the number of accidents is found for residential streets
      (about 25%), a somewhat smaller reduction is found for main roads (about 10%).
      Similar reductions are found in the number of property damage only accidents. The
      results of evaluation studies are robust with respect to study design. There is
      no evidence of publication bias in evaluation studies. Study findings are found
      to have high external validity.

PMID- 11235795
TI  - How do prolonged wakefulness and alcohol compare in the decrements they produce
      on a simulated driving task?
AB  - The effects of alcohol ingestion were compared with those of prolonged
      wakefulness on a simulated driving task. Eighteen healthy, male subjects aged
      between 19 and 35 years drove for 30 min on a simulated driving task at blood
      alcohol concentrations of 0.00, 0.05 and 0.08%. Subjective sleepiness was
      assessed before and after the driving task. Driving performance was measured in
      terms of the mean and standard deviation (S.D.) of lane position (tracking); the
      mean and S.D. of speed deviation (the difference between the actual speed and the
      posted speed limit); and the number of off-road occurrences. Ratings of
      sleepiness increased with increasing blood alcohol concentration, and were higher
      following the driving task. With increasing blood alcohol concentration, tracking
      variability, speed variability, and off-road events increased, while speed
      deviation decreased, the result of subjects driving faster. The results were
      compared with a previous study examining simulated driving performance during one
      night of prolonged wakefulness [Arnedt, J.T., MacLean A.W., 1996. Effects of
      sleep loss on urban and motorway driving stimulation performance. Presented at
      the Drive Alert... Arrive Alive International Forum, Washington DC], using an
      approach adopted by Dawson and Reid [Dawson, D., Reid, K., 1997. Fatigue, alcohol
      and performance impairment. Nature 388, 23]. For mean tracking, tracking
      variability, and speed variability 18.5 and 21 h of wakefulness produced changes
      of the same magnitude as 0.05 and 0.08% blood alcohol concentration,
      respectively. Alcohol consumption produced changes in speed deviation and off
      road occurrences of greater magnitude than the corresponding levels of prolonged
      wakefulness. While limited to situations in which there is no other traffic
      present, the findings suggest that impairments in simulated driving are evident
      even at relatively modest blood alcohol levels, and that wakefulness prolonged by
      as little as 3 h can produce decrements in the ability to maintain speed and road
      position as serious as those found at the legal limits of alcohol consumption.

PMID- 11235796
TI  - Bicycle helmet efficacy: a meta-analysis.
AB  - Bicycle helmet efficacy was quantified using a formal meta-analytic approach
      based on peer-reviewed studies. Only those studies with individual injury and
      helmet use data were included. Based on studies from several countries published
      in the period 1987-1998, the summary odds ratio estimate for efficacy is 0.40
      (95% confidence interval 0.29, 0.55) for head injury, 0.42 (0.26, 0.67) for brain
      injury, 0.53 (0.39, 0.73) for facial injury and 0.27 (0.10, 0.71) for fatal
      injury. This indicates a statistically significant protective effect of helmets.
      Three studies provided neck injury results that were unfavourable to helmets with
      a summary estimate of 1.36 (1.00, 1.86), but this result may not be applicable to
      the lighter helmets currently in use. In conclusion, the evidence is clear that
      bicycle helmets prevent serious injury and even death. Despite this, the use of
      helmets is sub-optimal. Helmet use for all riders should be further encouraged to
      the extent that it is uniformly accepted and analogous to the use of seat belts
      by motor vehicle occupants.

PMID- 11235797
TI  - Under-reporting of motor vehicle traffic crash victims in New Zealand.
AB  - Our aim was to ascertain the extent of under-reporting of seriously injured motor
      vehicle traffic crash victims, as recorded by police in New Zealand, and to what
      extent this coverage was biased by crash, injury, demographic, and geographic
      factors. Hospital data and police records were linked using probabilistic
      methods. During 1995, less than two-thirds of all hospitalised vehicle occupant
      traffic crash victims were recorded by the police. Reporting rates varied
      significantly by age, injury severity, length of stay in hospital, month of
      crash, number of vehicles involved, whether or not a collision occurred, and
      geographic region, but not by gender, ethnicity or day of the week of the crash.
      Those using these police files for prioritization, resource allocation and
      evaluation purposes need to be aware of the extent and nature of these biases
      contained within these databases.

PMID- 11235798
TI  - New evidence concerning fatal crashes of passenger vehicles before and after
      adding antilock braking systems.
AB  - Fatal crash rates for passenger cars and vans were compared for the last model
      year before four-wheel antilock brakes were introduced and the first model year
      for which antilock brakes were standard equipment. A prior study, based on fatal
      crash experience through 1995, reported that vehicle models with antilock brakes
      were more likely than identical but 1-year-earlier models to be involved in
      crashes fatal to their own occupants, but were less likely to be involved in
      crashes fatal to occupants of other vehicles. Overall, there was no significant
      effect of antilocks on the likelihood of fatal crashes. Similar analyses, based
      on fatal crash experience during 1996-98, yielded very different results. During
      1996-98, vehicles with antilock brakes were again less likely than earlier models
      to be involved in crashes fatal to occupants of other vehicles, but they were no
      longer overinvolved in crashes fatal to their own occupants.

PMID- 11235799
TI  - A statistical model to compare road mortality in OECD countries.
AB  - The objective of this paper is to compare safety levels and trends in OECD
      countries from 1980 to 1994 with the help of a statistical model and to launch
      international discussion and further research about international comparisons.
      Between 1980 and 1994, the annual number of fatalities decreased drastically in
      all the selected countries except Japan (+ 12%), Greece (+ 56%) and ex-East
      Germany (+ 50%). The highest decreases were observed in ex-West Germany (- 48%),
      Switzerland (- 44%), Australia (- 40%), and UK (- 39%). In France, the decrease
      in fatalities over the same period reached 34%. The fatality rate, an indicator
      of risk, decreased in the selected countries from 1980 to 1994 except in the east
      European countries during the motorization boom in the late 1980s. As fatality
      rates are not sufficient for international comparisons, a statistical multiple
      regression model is set up to compare road safety levels in 21 OECD countries
      over 15 years. Data were collected from IRTAD (International Road Traffic and
      Accident Database) and other OECD statistical sources. The number of fatalities
      is explained by seven exogenous (to road safety) variables. The model, pooling
      cross-sectional and time series data, supplies estimates of elasticity to the
      fatalities for each variable: 0.96 for the population; 0.28 for the vehicle fleet
      per capita; -0.16 for the percentage of buses and coaches in the motorised
      vehicle fleet; 0.83 for the percentage of youngsters in the population; - 0.41
      for the percentage of urban population; 0.39 for alcohol consumption per capita;
      and 0.39 for the percentage of employed people. The model also supplies a rough
      estimate of the safety performance of a country: the regression residuals are
      supposed to contain the effects of essentially endogenous and unobserved
      variables, independent to the exogenous variables. These endogenous variables are
      safety performance variables (safety actions, traffic safety policy, network
      improvements and social acceptance). A new indicator, better than the mortality
      rate, is then set upon the residuals. Mean estimates of this indicator for the
      years 1980-1982 and the years 1992-1994 rank the countries in the beginning and
      at the end of the study period. Countries showing the best ranks (and thus the
      best performance) in 1980 and 1994 are Sweden, the Netherlands and Norway. The UK
      and Switzerland reach the top 5 in 1994. Greece, Belgium, Portugal and Spain are
      the last countries in the classification along with, surprisingly, the USA.
      France was ranked 18th in 1980 and 15th in 1994 but is ranked amongst the five
      countries that most improved from 1980 to 1994. This model remains non definitive
      because it is not able to distinguish between safety performance and unobserved
      exogenous variables although these exogenous variables could explain more about
      the differences in levels and trends between the countries. More complex models,
      particularly highly sophisticated models regarding the number of fatalities with
      breakdowns by road users or road classes would be needed to give a precise and
      profound ranking of safety levels and safety improvements between countries.

PMID- 11235800
TI  - Predicting performance of annual safety outcomes.
AB  - A control chart system was developed in an earlier paper to identify the
      occurrence of actual risk changes or deviation from the expected levels of road
      crash fatalities during the course of a year. This paper discusses the
      development of a prediction method for estimating number of fatalities during a
      year. The method then provides a mechanism for estimating the likelihood of
      meeting a pre-set target or any other outcome. At any point of time in a year,
      the attainability of a target for the year, depends not only on safety outcomes
      during the remainder of the year but also on outcomes up to that point in the
      year. High week to week variability would indicate that it can be difficult to
      achieve the intended maximum goal. The control charts developed earlier, indicate
      if the current trend differs from the expected trend or that required to achieve
      the target. This paper determines the probability of achieving the target given
      the past outcomes of the year. It also determines the level of outcome for the
      year based on the past trend and in the absence of any special programmes. The
      paper discusses the New Zealand application as an example.

PMID- 11235801
TI  - The crash reduction effectiveness of a network-wide traffic police deployment
      system.
AB  - Random Road Watch (RRW) is a traffic policing program in operation in Queensland,
      Australia. It differs from conventional traffic policing in that an explicit
      resource management technique is used which randomly schedules low levels of
      police enforcement in a manner intended to provide long-term, widespread coverage
      of a road network and hence maximise road safety benefits. Implementation of the
      program studied in Queensland covered 55% of total crashes within the state. This
      study aimed to measure the crash effects of the RRW program in Queensland. A
      quasi-experimental study design was used for the evaluation incorporating Poisson
      regression statistical analysis techniques. Analysis of the effects of the
      Queensland RRW program on crash frequency has shown the program to be effective
      overall. Estimated program effects were largest on fatal crashes, with an
      estimated reduction of 31%. Estimated aggregate program crash effects reduced
      with crash severity and increased with time after program introduction. Crash
      reductions in the third year after program introduction translated into savings,
      at state level, of some 12% of the state's crashes of all severities and some 15%
      of the state's fatal road crashes. Overall, the program produced a significant
      11% reduction in total crashes in areas outside of metropolitan Brisbane. The
      opportunity-cost benefit/cost ratio for the program was estimated to be 55:1.

PMID- 11235802
TI  - Partners for child passenger safety: a unique child-specific crash surveillance
      system.
AB  - Insurance claims data were combined with telephone survey and on-site crash
      investigation data to create the first large scale, child-focused motor vehicle
      crash surveillance system in the US. Novel data management and transfer
      techniques were used to create a nearly real-time data collection system. In the
      first year of this on-going project, known as Partners for Child Passenger
      Safety, over 1200 children < or = 15 years of age per week were identified in
      crashes reported to State Farm Insurance Co. from 15 states and Washington, D.C.
      Partners for Child Passenger Safety is similar in its design and overall
      objectives to National Automotive Sampling System (NASS), the only other
      population-based crash surveillance system currently operating in the US.

PMID- 11235803
TI  - Factors related to driving difficulty and habits in older drivers.
AB  - OBJECTIVES: To evaluate the association between chronic medical conditions,
      functional, cognitive, and visual impairments and driving difficulty and habits
      among older drivers. DESIGN: Cross-sectional study. SETTING: Mobile County,
      Alabama. PARTICIPANTS: A total of 901 residents of Mobile County, Alabama aged 65
      or older who possessed a driver's license in 1996. MEASUREMENTS: Information on
      demographic characteristics, functional limitations, chronic medical conditions,
      driving habits, and visual and cognitive function were collected via telephone.
      The three dependent variables in this study were difficulty with driving, defined
      as any reported difficulty in > or = 3 driving situations (e.g. at night), low
      annual estimated mileage, defined as driving less than 3000 miles in 1996, and
      low number of days ( < or = 3) driven per week. RESULTS: A history of falls,
      kidney disease or stroke was associated with difficulty driving. Older drivers
      with a history of kidney disease were more likely to report a low annual mileage
      than subjects without kidney disease. Low annual mileage was also associated with
      cognitive impairment. In general, older drivers with a functional impairment were
      more likely to drive less than 4 days per week. Older drivers with a history of
      cataracts or high blood pressure were more likely to report a low number of days
      driven per week, while subjects with visual impairment were at increased risk of
      experiencing difficulty driving as well as low number of days driven per week.
      CONCLUSIONS: The results underscore the need to further understand the factors
      negatively affecting driving independence and mobility in older drivers, as well
      as the importance of improved communication between older adults and health care
      professionals regarding driving.

PMID- 11235804
TI  - Secular trends of motor vehicle mortality in the United States, 1910-1994.
AB  - To examine the secular trends of mortality from motor vehicle crashes, the
      authors compiled annual population and mortality data for the United States from
      1910 to 1994 and performed an age-period-cohort analysis through graphical
      presentation, median polish, and Poisson regression modeling. During the 85-year
      study period, death rates from motor vehicle crashes showed two peaks, first in
      1935-39 and then in 1965-69. Age and period effects accounted for 94% of the
      variation in motor vehicle mortality in men and 84% of the variation in women.
      Age patterns of motor vehicle mortality varied greatly with birth cohorts: for
      those who were born before 1910, death rates increased with age; for those born
      after 1910, death rates peaked at age 20-24 years for men and at age 15-19 years
      for women. A crossover characterized by a downward trend in death rates among the
      elderly and an upward trend among adolescents and young adults was observed in
      both sexes. The complex age, period, and cohort patterns of motor vehicle
      mortality are likely to have been shaped by changes in traffic patterns and
      driver behavior, and by improvements in safety design and emergency medical
      service systems.

PMID- 11235805
TI  - Gene medicine : a new field of molecular medicine.
AB  - Gene therapy has emerged as a new concept of therapeutic strategies to treat
      diseases which do not respond to the conventional therapies. The principle of
      gene therapy is to introduce genetic materials into patient cells to produce
      therapeutic proteins in these cells. Gene therapy is now at the stage where a
      number of dinical trials have been carried out to patients with gene-deficiency
      disease or cancer. Genetic materials for gene therapy are generally composed of
      gene expression system and gene delivery system. For the dinical application of
      gene therapy in a way which conventional drugs are used, researches have been
      focused on the design of gene delivery system which can offer high transfection
      efficiency with minimal toxicity. Currently, viral delivery systems generally
      provide higher transfection efficiency compared with non-viral delivery systems
      while non-viral delivery systems are less toxic, less immunogenic and
      manufacturable in large scale compared with viral systems. Recently, novel
      strategies towards the design of new non-viral delivery system, combination of
      viral and non-viral delivery systems and targeted delivery system have been
      extensively studied. The continued effort in this area will lead us to develop
      gene medicine as 'gene as a drug' in the near future.

PMID- 11235806
TI  - Synthesis of 2-(allylthio)pyrazines as a novel cancer chemopreventive agent.
AB  - 2-(Allylthio)pyrazine derivatives were designed as a novel cancer chemopreventive
      agent that functions through selective inhibtion of cytochrome P-450 and
      induction of phase II enzymes involved in the detoxification of carcinogens. A
      practical preparation method of 2-(allylthio) pyrazine derivatives was
      established by the reaction of 2-mercaptopyrazine and allylbromides in the
      presence of a catalytic antioxidant, DABCO (1,4-diazabicyclo[2,2,2] octane), in
      dimethylformamide at below 50 degrees C.

PMID- 11235807
TI  - Synthesis and antihypertensive activity of certain Mannich Bases of 2
      ethoxycarbonylindoles and 5H-pyridazin.
AB  - This manuscript reports the synthesis of two series of Mannich Bases 3-12 and 21
      40 obtained respectively by the reaction of either 2-ethoxycarbonylindoles 1-2 or
      5H-pyridazino [4,5b]inoles 17-20 as a substrate with formalin and the appropriate
      2 degrees amines under the suitable Mannich conditions. Fourteen of the
      synthesized Mannich basese were screened as antihypetensive agents in
      normotensive anesthetized rats. The effect of compound 4 in normotensive
      anesthetized dogs was also studied.

PMID- 11235808
TI  - Synthesis and preliminary antimicrobial screening of new benzimidazole
      heterocycles.
AB  - A series of 2-methylbenzimidazole incorporated to different heterocycles through
      ethyl or carbamoylethyl groups at position 1 of benzimidazole were synthesized.
      Also 3-(2-methylbenzimidazol-1-yl)propanoic acid hydrazide incorporated with
      semicarbazides and thiosemicarbazides were prepared. Moreover, the triazole 5e
      underwent Michael addition and alkylation reaction. Some of the newly synthesized
      compounds showed considerable antimicrobial activity against gram positive,
      negative bacteria and yeast.

PMID- 11235809
TI  - Naphthazarin derivatives (VII): antitumor action against ICR mice bearing ascitic
      S-180 cells.
AB  - Various analogues of 5,8-dimethoxy-1,4-naphthoquinone (DMNQ) such as 2- or 6-(1
      hydroxyiminoalkyl)-DMNQs were prepared and evaluated for the antitumor action. (1
      Hydroxyiminoalkyl)-DMNQ derivatives expressed greater antitumor action than (1
      hydroxyalkyl)- or acyl-DMNQ derivatives. Moreover, 6-(1-hydroxyiminoalkyl)-DMNQ
      derivatives expressed higher antitumor action than 2-sudstituted ones, suggestive
      of a steric effect. Some of 6-(1-propyloxyalkyl)-DMNQ derivatives with an alkyl
      group of butyl to octyl moiety showed T/C values of >400%

PMID- 11235810
TI  - Photocleavage of DNA by 4'-bromoacetophenone analogs.
AB  - 4'-Bromoacetophenone analogs, which are able to generate monophenyl radicals
      capable of hydrogen atom abstraction, were investigated as possible
      photoinducible DNA cleaving agents. The potential of 4'-bromoacetophenone as a
      possible new DNA cleaver is explored. Pyrrolecarboxatmid conjugated 4'
      bromoacetophenones, in particular, DNA cleaving activity and sequence-selectivity
      on the contiguous AT base pair sites.

PMID- 11235811
TI  - Constituents and the antitumor principle of Allium victorialis var. platyphyllum.
AB  - To search for cytotoxic components from Allium victorialis, MTT assays on each
      extract and an isolated component, gitogenin 3-O-lycotetroside, were performed
      against cancer cell lines. Cytotoxicities of most extract were shown to be
      comparatively weak, though IC50 values of CHCl3 fraction was found to be <31.3
      368.4 microg/ml. From the incubated methanol extract at 36 degrees C, eleven
      kinds of organosulfuric flavours were predictable by GC-MS performance. The most
      abundant peak was revealed to be 2-vinyl-4H-1,3-dithiin (1) by its mass spectrum.
      Further, this extract showed significant cytotoxicities toward cancer cell lies.
      Silica gel column chromatography of the n-butanol fraction led to the isolation
      of gitogenin 3-O-lycotetroside (3) along with astragalin (4) and kaempferol 3, 4'
      di-O-beta-D-glucoside (5). This steroidal saponin exhibited significant cytotoxic
      activities (IC50, 6.51-36.5 microg/ml) over several cancer cell lines. When
      compound 3 was incubated for 24 h with human intestinal bacteria, a major
      metabolite was produced and then isolated by silica gel column chromatography. By
      examining parent- and prominent ion peak in FAB-MS spectrum of the metabolite,
      the structure was speculated not to be any of prosapogenins of 3, suggesting that
      spiroketal ring were labile to the bacterial reaction. These suggest that
      disulfides produced secondarily are the antitumor principles.

PMID- 11235812
TI  - Monoamine oxidase B inhibitors from the fruits of Opuntia ficus-indica var.
      saboten.
AB  - Three varieties of methyl citrate and 1-methyl malate were isolated from the
      fruits of Opuntia ficus-indica var. saboten Makino through in vitro bioassay
      guided isolation for the inhibition on monoamine oxidase(MAO). The IC50 values
      for MAO-B of 1-monomethyl citrate, 1,3-dimethyl citrate, trimethyl citrate and 1
      methyl malate were 0.19, 0.23, 0.61 and 0.25 mM, respectively. However, on MAO-A,
      their inhibitions showed only marginal activity.

PMID- 11235813
TI  - Studies on the possible mechanisms of protective activity against alpha-amanitin
      poisoning by aucubin.
AB  - Aucubin, an iridoid glucoside, was investigated to determine whether it has a
      stimulating effect on alpha-amanitin excretion in alpha-amanitin intoxicated
      rats, and whether there is binding activity to calf thymus DNA. High-performance
      liquid chromatography (HPLC) analysis of alpha-amanitin in rat urine allowed
      quantitative measurement of the alpha-amanitin concentration with a detection
      limit of 50 ng/ml. In this system, a group treated with both alpha-amanitin and
      aucubin showed that alpha-amanitin was excreted about 1.4 times faster than in
      the alpha-amanitin only treated group. Our previous results showed that the
      toxicity of alpha-amanitin is due to specific inhibition of RNA polymerase
      activity and the resultant blockage of the synthesis of certain RNA species in
      the nucleus. However, no significant activity change on RNA polymerase from Hep
      G2 cells was observed when aucubin was treated with alpha-amanitin at any
      concentration tested. Nevertheless, aucubigenin inhibited both DNA polymerase
      (IC50, 80.5 microg/ml) and RNA polymerase (IC50, 135.0 microg/ml) from the Hep G2
      cells. The potential of both alpha-amanitin and aucubin to interact with DNA were
      examined by spectrophotometric analysis. Alpha-Amanitin showed no significant
      binding capacity to calf thymus DNA, but aucubin was found to interact with DNA,
      and the apparent binding constant (Kapp) and apparent number of binding sites per
      DNA phosphate (Bapp) were 0.45 x 10(4) M(-1) and 1.25, respectively.

PMID- 11235814
TI  - NMDA receptor and NO mediate ET-1-induced behavioral and cardiovascular effects
      in periaqueductal gray matter of rats.
AB  - Endothelin-1 (ET-1), a novel and potent vasoconstrictor in blood vessel, is known
      to have some functions in the rat central nervous system (CNS). In order to
      investigate the central functions of ET-1, ET-1 was administered to the
      periaqueductal gray area (PAG) of anesthetized rats to induce barrel rolling and
      increase the arterial blood pressure (ABP). ET-1 had a modulatory effect on
      central cardiovascular and behavioral control. The selective N-methyl-D-aspartate
      (NMDA) receptor antagonist MK-801 (3 micromol/kg, i.p.) blocked the ET-1 induced
      responses, and both the nitric oxide synthase (NOS) inhibitor L-NAME (N-nitro-L
      arginine methylester 1 mmol/rat) and the nitric oxide (NO) scavenger hemoglobin
      (15 nmol/rat) had similar effects in reducing the ET-1 (10 pmol/rat)-induced
      behavioral changes and ABP elevation. However, NO donor sodium nitroprusside (SNP
      10 microg, 1 microg/rat) decreased the ET-1 induced ABP elevation, and recovered
      the ET-1-induced barrel rolling effect that was reduced by MK-801. These results
      suggest that ET-1 might have neuromodulatory functions such as ABP elevation and
      barrel rolling induction in the PAG of the rats via the NMDA receptor and NO.

PMID- 11235815
TI  - Albumin release from biodegradable hydrogels composed of dextran and
      poly(ethylene glycol) macromer.
AB  - Biodegradable hydrogels based on glycidyl methacrylate dextran (GMD) and
      dimethacrylate poly(ethylene glycol) (DMP) were proposed for colon-specific drug
      delivery. GMD was synthesized by coupling of glycidyl methacrylate with dextran
      in the presence of 4-(N,N-dimethyl-amino)pyridine (DMAP) using dimethylsulfoxide
      as a solvent. Methacrylate-terminated poly (ethylene glycol) (PEG) macromer was
      prepared by the reaction of PEG with methacryloyl chloride. GMD/DMP hydrogels
      were prepared by radical polymerization of phosphate buffer solution (0.1M, pH
      7.4) of GMD and DMP, using ammonium peroxydisulfate (APS) and UV as initiating
      system. The synthetic GMD, DMP, and GMD/DMP hydrogels were characterized by
      fourier transform infrared (FT-IR) spectroscopy. The FITC-albumin loaded
      hydrogels were prepared by adding FITC-albumin solution before UV irradiation.
      Swelling capacity of GMD/DMP hydrogels was controlled not only by molecular
      weight of dextran, but also by incorporation ratio of DMP Degradation of the
      hydrogels has been studied in vitro with dextranase. FITC-albumin release from
      the GMD/DMP hydrogels was affected by molecular weight of dextran and the
      presence of dextranase in the release medium.

PMID- 11235816
TI  - Mode of antiviral activity of water soluble components isolated from Elfvingia
      applanata on vesicular stomatitis virus.
AB  - A preparation of water soluble components (EA) was made from carpophores of
      Elfvingia applanata (Pers.) Karst and its in vitro antiviral activity on
      vesicular stomatitis virus [(Indiana serotype, VSV(IND)] was investigated by
      plaque reduction assay. EA exhibited potent antiviral activity on VSV(IND) growth
      and negligible cytotoxicity on Vero cells, 50% effective concentration (EC50) of
      104 microg/ml and 50% cytotoxic concentration (CC50) of 3,793 microg/ml,
      respectively. Selectivity index (SI, CC50/EC50) of EA on Vero cell and VSV(IND)
      was about 36.5. EA did not display either a direct virucidal effect on VSV(IND)
      or induction of antiviral substance by Vero cells upon its treatment. Thus, the
      mode of antiviral activity of EA was studied at steps of viral adsorption onto
      cell. When both EA and virus were added to cell monolayers, titer of cell-free
      virus in culture supernatant increased in ca. 30-40% compared with that of
      control group and titer of cell-associated virus was 60-100% higher than that of
      control group. These results suggested that antiviral activity of EA on VSV(IND)
      might be due to the hindrance of viral entry to cells at either endocytosis or
      loss of envelope.

PMID- 11235818
TI  - Troglitazone and liver function abnormalities: lessons from a prescription event
      monitoring study and spontaneous reporting.
AB  - OBJECTIVES: To investigate whether there were any cases of liver function
      abnormalities possibly associated with troglitazone use in general practice in
      England. DESIGN: A prescription-event monitoring (PEM) study was undertaken
      between October 1997 and December 1997. SETTING: Data from prescriptions were
      obtained electronically for the troglitazone cohort in the immediate
      postmarketing period. STUDY PARTICIPANTS: Event data were obtained for a total of
      1344 patients. RESULTS: Troglitazone was effective in 394 (75%) of the 529
      patients for whom an opinion was given. The most frequent reasons for stopping
      treatment related to drug tolerability were malaise/lassitude (16 reports),
      abnormal liver function tests (II reports) and nausea/vomiting (9 reports). The
      major cause of stopping troglitazone was because the drug was withdrawn from the
      market (1101 reports). 30 patients with liver dysfunction were identified from
      the cohort. In 9 of these patients there were alternative explanations for the
      liver dysfunction and hence these patients were not followed up further. 21
      patients were followed up, for whom 19 questionnaires were returned. In 5
      patients their liver dysfunction was assessed as possibly related to
      troglitazone, in 6 patients the liver dysfunction was unlikely to be attributed
      to troglitazone, while in 7 patients it was difficult to assess the causality
      because of limited information and confounding factors. The remaining patient was
      not included as this individual did not fit the inclusion criteria of the study.
      CONCLUSION: Although the cohort is small (the drug was available for only 3
      months in the UK), 5 patients with abnormal liver function, considered possibly
      related to troglitazone were detected in this PEM study. It is possible for PEM
      to contribute to the elucidation of safety signals in the UK.

PMID- 11235819
TI  - Incompleteness of lamotrigine data.

PMID- 11235817
TI  - Safety of antihistamines in children.
AB  - The histamine H1 receptor antagonists (antihistamines) are an important class of
      medications used for the relief of common symptoms associated with
      hyperhistaminic conditions occurring in children and adults. This group of drugs
      may be subdivided into 3 classes, or generations, based upon their propensity to
      induce sedation and cardiotoxicity. The first generation (classical)
      antihistamines are highly effective in treating hyperhistaminic conditions.
      However, they frequently induce sedation and may adversely affect a child's
      learning ability. First generation antihistamine-induced sedation has been
      described to occur in more than 50% of patients receiving therapeutic dosages.
      Serious adverse events are unusual following overdoses of first generation
      antihistamines although life-threatening adverse events have been described. When
      the so-called 'second generation' antihistamines terfenadine and astemizole were
      introduced they were widely embraced and quickly used by clinicians of all
      specialities, including paediatricians, as nonsedating alternatives to the first
      generation compounds. These new agents were found to be equally or more effective
      than first generation antihistamines in relieving symptoms associated with
      hyperhistaminic conditions without the soporific effects of the first generation
      agents. Unfortunately, after approximately 10 years of widespread clinical use,
      disturbing reports of potentially life-threatening dysrhythmias, specifically
      torsades de pointes, were described. Both terfenadine and astemizole have been
      shown in vitro to inhibit several ion channels, and in particular the delayed
      outward rectifier potassium channel in the myocardium, predisposing the heart to
      dysrhythmias. The potential life-threatening cardiotoxicities of the second
      generation antihistamines led to the search for noncardiotoxic and nonsedating
      agents. Loratadine, fexofenadine, mizolastine, ebastine, azelastine and
      cetirizine are the first of the new third generation antihistamines. These drugs
      have been shown to be efficacious with few adverse events including no clinically
      relevant cytochrome P450 mediated metabolic-based drug-drug interactions or QT
      interval prolongation/cardiac dysrhythmias. Appropriate treatment of an
      antihistamine overdose depends upon which class of compound has been ingested.
      There is no specific antidote for antihistamine overdose and treatment is
      supportive particularly for ingestions of first generation compounds. Ingestion
      of excessive doses of terfenadine or astemizole requires immediate medical
      attention. Children who accidentally ingest excessive doses of a third generation
      compound may usually be adequately managed at home. However, patients ingesting
      large amounts (approximately >3 to 4 times the normal therapeutic daily dose)
      should receive medical attention. These patients should be monitored for 2 to 3
      hours after the ingestion and patients ingesting cetirizine should be advised
      about the potential for sedation. The availability of newer generation
      antihistamine compounds has clearly added to the clinical effectiveness and
      patient tolerance of a widely prescribed class of drugs. These advances have also
      been accompanied by improved safety profiles, particularly in the case of third
      generation antihistamine overdose.

PMID- 11235820
TI  - What will be the role of pharmacogenetics in evaluating drug safety and
      minimising adverse effects?
AB  - In the US, adverse drug reactions (ADRs) rank between the fourth to sixth leading
      cause of death, ahead of pneumonia and diabetes mellitus. An important reason for
      the high incidence of serious and fatal ADRs is that the existing drug
      development paradigms do not generate adequate information on the mechanistic
      sources of marked variability in pharmacokinetics and pharmacodynamics of new
      therapeutic candidates, precluding treatments from being tailored for individual
      patients. Pharmacogenetics is the study of the hereditary basis of person-to
      person variations in drug response. The focus of pharmacogenetic investigations
      has traditionally been unusual and extreme drug responses resulting from a single
      gene effect. The Human Genome Project and recent advancements in molecular
      genetics now present an unprecedented opportunity to study all genes in the human
      genome, including genes for drug metabolism, drug targets and postreceptor second
      messenger machinery, in relation to variability in drug safety and efficacy. In
      addition to sequence variations in the genome, high throughput and genome-wide
      transcript profiling for differentially regulated mRNA species before and during
      drug treatment will serve as important tools to uncover novel mechanisms of drug
      action. Pharmacogenetic-guided drug discovery and development represent a
      departure from the conventional approach which markets drugs for broad patient
      populations, rather than smaller groups of patients in whom drugs may work more
      optimally. Pharmacogenetics provides a rational framework to minimise the
      uncertainty in outcome of drug therapy and clinical trials and thereby should
      significantly reduce the risk of drug toxicity.

PMID- 11235822
TI  - Self-reported skin problems among physical processors in the chemical industry in
      Great Britain.
AB  - Contact dermatitis is common in the chemical industry. A cross-sectional study
      was conducted to investigate the prevalence of self-reported skin problems in
      employees involved in the drying, blending, milling, grinding and filling/bagging
      end of chemical manufacture in small- to medium-sized contract
      manufacturing/processing chemical companies in Great Britain. There were several
      secondary aims. Twenty-three per cent of the employees interviewed reported
      having had a skin problem in the previous 12 months. Of those reporting problems,
      46% were always/nearly always involved in blending and 56% were always/nearly
      always involved in filling and bagging. These same processes were also more
      commonly associated with continuous or recurring skin problems. Seventy-five per
      cent reported a problem involving the upper limbs; most had more than one body
      area affected. Forty-three per cent had consulted a doctor (67% their general
      practitioner) and 9% took time off work as a result of their skin condition. Skin
      problems seemed to peak (34% employees) in those who had spent between 1 and 2
      years in their current job. Solvents, known skin irritants, were the most
      frequent, single category of chemicals encountered in the study. Over 92% had
      been told how to avoid skin problems; 85% reported that they always/almost always
      wore protective clothing. Despite these measures, a significant number had
      reported having had a skin problem related to their work in the previous 12
      months. Particular attention to control measures based on risk assessment is
      recommended for these physical processors in the chemical industry. Further
      research is also recommended into the whole area of personal protective clothing
      and the individual worker's perception of risks to health in the workplace.

PMID- 11235821
TI  - Thalomid (Thalidomide) capsules: a review of the first 18 months of spontaneous
      postmarketing adverse event surveillance, including off-label prescribing.
AB  - The sedative/hypnotic thalidomide was withdrawn from the worldwide market nearly
      40 years ago, because of its teratogenic and neurotoxic effects. Thalidomide was
      later found to very effectively suppress erythema nodosum leprosum (ENL). The US
      Food and Drug Administration (FDA) has approved Thalomid (thalidomide) capsules
      for the acute treatment of the cutaneous manifestations of moderate to severe
      ENL. Thalidomide is currently under investigation for the treatment of a wide
      variety of diseases, including conditions thought to have an inflammatory or
      immune basis, malignancies and complications of infection with HIV. Interest in
      the potential anti-inflammatory, immunomodulatory and anti- angiogenic effects of
      thalidomide has resulted in off-label use of prescription thalidomide. During the
      first 18 months of spontaneous postmarketing adverse event surveillance for
      Thalomid, 1210 spontaneous postmarketing adverse event reports were received for
      patients treated with prescription thalidomide for all therapeutic indications,
      including off-label use. The most common adverse events spontaneously reported
      would have been expected on the basis of the current Thalomid labelling/product
      information. The current labelling/product information reflects what was known
      about the risks associated with thalidomide therapy in limited patient
      populations at the time of the approval of Thalomid. With the postmarketing use
      of thalidomide in populations other than patients with ENL, it becomes
      increasingly important to identify patient groups that may be particularly
      susceptible to specific adverse drug effects and to identify conditions under
      which specific adverse events may be more likely to occur. Oncology patients may
      represent a patient population with increased susceptibility to thalidomide
      associated adverse effects, including thromboembolic events. Consideration of the
      spontaneous postmarketing safety surveillance data may help to identify and
      characterise factors associated with increased risk in this and other patient
      groups. Serious unexpected adverse events reported with sufficient frequency to
      signal previously undetected product-event associations for which there may
      potentially be plausible evidence to suggest a causal relationship have included
      seizures and Stevens-Johnson syndrome. The potential effects of thalidomide on
      wound healing are also being closely monitored. Premarketing human clinical
      trials of drug products are inherently limited in their ability to detect adverse
      events. Broader postmarketing experience with thalidomide in more varied patient
      populations and more experience in the setting of long term thalidomide use will
      increase our ability to detect rare adverse events and to identify signals that
      may need to be evaluated in more controlled settings.

PMID- 11235823
TI  - Biological monitoring and exposure to mercury.
AB  - Occupational health professionals' interest in controlling mercury (Hg) exposure,
      and the use of biological monitoring in this context, has been ongoing for a
      number of years. Evidence from urinary Hg results in a number of UK firms who
      have undertaken some form of biological monitoring or occupational health
      surveillance suggest that exposure has decreased over the last 10-15 years. This
      decrease precedes the establishment in the UK of an advisory biological
      monitoring guidance value (HGV) for urinary Hg and the production of updated
      medical guidance from the Health & Safety Executive on Hg exposure (MS12 1996).
      This latter document recommends a urinary sampling interval for urinary Hg of
      between 1 and 3 months, which is consistent with the reported toxicokinetics of
      Hg excretion, but we highlight that urinary Hg represents integrated exposure
      over many previous months. Mercury is a recognized nephrotoxin and MS12 1996
      mentions the use of regular dipstick protein estimations. We review our
      experience of investigating proteinuria and enzymuria in a large-scale cross
      sectional occupational study. The incidence of Hg-induced renal disease is
      probably very rare at current exposure levels. Therefore acceptance of a high
      false-positive rate of proteinuria not related to Hg exposure needs to be
      considered in any urinary protein testing regime of Hg workers. The establishment
      of an HGV for urinary Hg has raised questions about the uncertainty associated
      with a urinary Hg result, including factors such as diurnal variation, whether
      urine correction by creatinine or specific gravity is preferable and the
      possibility of non-occupational sources of Hg contributing significantly towards
      breaching the HGV. Correction of urinary Hg results by creatinine or specific
      gravity and the use of a fixed sampling time, such as the beginning or end of the
      day, substantially reduce the uncertainty in a urinary Hg measurement. But even
      with good laboratory precision, an individual with a true urinary Hg excretion of
      20 nmol/mmol creatinine could supply urine samples of between 14 and 26 nmol/mmol
      creatinine. The influence of dietary sources in the UK contributing to urinary Hg
      values approaching or exceeding the HGV is unlikely. The use of tribal or ethnic
      cosmetics and remedies needs to be considered if a urinary Hg result looks
      inappropriately high, as some such preparations have been found to contain Hg and
      can be absorbed through the skin. The ability of excessive chewers or teeth
      grinders who have a large number of dental amalgam fillings to breach the urinary
      HGV in the absence of substantial occupational Hg exposure has been reported in a
      few Scandanavian studies. We report here a likely case of this phenomenon. Since
      the establishment of the HGV, our biological monitoring Hg data from a number of
      industry sectors using inorganic or metallic Hg have suggested that a minority of
      samples (13%) are still greater than the HGV.

PMID- 11235824
TI  - Mobile phone use and subjective symptoms. Comparison of symptoms experienced by
      users of analogue and digital mobile phones.
AB  - In 1995 many people reported symptoms such as headaches, feelings of discomfort,
      warmth behind/around or on the ear and difficulties concentrating while using
      mobile phones. The number of complaints was higher for people using the digital
      (GSM) system, i.e. with pulse modulated fields, than for those using the analogue
      (NMT) system. Our main hypothesis was that GSM users experience more symptoms
      than NMT users. An epidemiological investigation was initiated including 6379 GSM
      users and 5613 NMT 900 users in Sweden, and 2500 from each category in Norway.
      The adjusted odds ratio did not indicate any increased risk for symptoms for GSM
      users compared with NMT 900 users. Our hypothesis was therefore disproved.
      However, we observed a statistically significant lower risk for sensations of
      warmth on the ear for GSM users compared with NMT 900 users. The same trend was
      seen in Norway for sensations of warmth behind/around the ear and in Sweden for
      headaches and fatigue. Factors distinguishing the two systems (radio frequency
      emission, phone temperatures and various ergonomic factors) may be responsible
      for these results, as well as for a secondary finding: a statistically
      significant association between calling time/number of calls per day and the
      prevalence of warmth behind/around or on the ear, headaches and fatigue.

PMID- 11235825
TI  - How a sample of businesses in the West Midlands (UK) are currently managing
      vibration exposure.
AB  - This paper discusses the results of a local initiative in the West Midlands (UK)
      which looked at how businesses in engineering, utilities and foundry trades
      managed the risks from hand-arm vibration. Inadequacies of health surveillance
      programmes and the need for enforcement action are outlined.

PMID- 11235826
TI  - Provision and perception of occupational health in small and medium-sized
      enterprises in Sheffield, UK.
AB  - A random sample of managers of small and medium-sized enterprises (SMEs) was
      selected from a database of businesses in Sheffield, UK. They were invited to
      take part in a study to evaluate the provision and perception of occupational
      health in SMEs in Sheffield. The study used an interviewer-led questionnaire,
      which collected quantitative and qualitative data; each interview took
      approximately 40 min to complete. Several approaches to recruitment were adopted
      during the study. Twenty-eight managers were interviewed over the 6 month study
      period. All of the SMEs employed <250 people; 43.2% did not have or had never
      reviewed a written health and safety policy. Only 18% had a written occupational
      health policy; 14.4% employed the services of a part-time occupational health
      physician; 7.2% employed a health and safety advisor; and 10.8% employed a part
      time occupational health nurse. Twenty-five per cent had a nominated person
      responsible for occupational health and 67% thought that a doctor or nurse would
      be the best person to provide an occupational health service. Twenty-eight per
      cent of the companies carried out some form of pre-employment screening and 14.2%
      carried out health promotion. Fifteen (53.5%) collected some form of health
      related absence data. Eight companies (28.6%) organized a formal induction
      programme for all new employees. Further work should be undertaken in an attempt
      to improve access to local industry and particularly to SMEs. This study has
      clearly shown that access is possible, but different strategies of approach were
      required before a workable strategy could be found. Undoubtedly, this access can
      be improved by better understanding of the interaction between researchers,
      occupational health providers and local managers of SMEs.

PMID- 11235827
TI  - Environmental factors and heatstroke.
AB  - The objective of this study was to determine the extent of the influence of
      temperature and humidity on the number of heatstroke presentations. Three hundred
      and forty-five labourers presented to the Accident and Emergency Hospital in Abu
      Dhabi with heatstroke during a 3 month summer period. There was no significant
      predictive association between the maximum daily temperature and/or humidity and
      the presentation of heatstroke. There was no significant association with the
      maximum temperature on the previous day, day of the week or temperature trend.
      The largest statistical correlation was between the maximum temperature and
      humidity and the log of the number of cases. It is possible that there are other
      significant explanatory variables that we have not included in the model.

PMID- 11235828
TI  - Job stress and dissatisfaction in association with non-fatal injuries on the job
      in a cross-sectional sample of petrochemical workers.
AB  - This cross-sectional study analysed the frequency and severity of work stressors
      and job satisfaction at workplaces in relation to work-related non-fatal injuries
      amongst a sample of petrochemical workers in Taiwan. The study participants
      consisted of 568 cases injured on the job between 1991 and 1997, and 954 injury
      free controls matched to cases on frequencies of age, sex and work site. After
      adjusting for potential confounders, we found that cases were more likely than
      controls to report stressors with a higher frequency [odds ratio (OR) = 1.4, 95%
      confidence interval (CI) = 0.9-2.0] and a more severe reaction (OR = 1.3, 95% CI
      = 0.9-1.8). The dose-response analyses further indicated that the OR of injury
      was monotonically associated with stress reaction only (P for test for trend of
      ORs = 0.02). Job satisfaction, though, was unrelated to non-fatal injury.
      Although the cross-sectional nature of our study precludes a causal inference
      between stress reaction to stressors and risk of developing non-fatal injuries,
      our results tend to suggest that the severity of stress reaction is more
      associated with occupational non-fatal injury than is the frequency of stress or
      job dissatisfaction.

PMID- 11235829
TI  - The effect of noise on serum and urinary magnesium and catecholamines in humans.
AB  - We have studied whether a short-term exposure to loud noise was able to modify
      urinary catecholamine excretion and serum concentration and urinary excretion of
      magnesium and other related electrolytes. In 25 healthy volunteers, blood and
      urine concentrations of magnesium, calcium, phosphorus and creatinine, and
      urinary catecholamines were measured before and after exposure to noise in an
      industrial plant. Samples were collected at 08:00 h on the day of the experiment
      and soon after noise exposure (at 20:00 h). Two further urine samples were
      collected the following day and 2 days after the experiment, always at 08:00 h in
      the morning. The sound energy average level was 98 dB(A), but peak levels reached
      108 dB(A). Urinary catecholamines were determined by high-performance liquid
      chromatography. Serum magnesium and calcium were significantly increased after
      exposure to noise, whereas phosphorus displayed a similar but non-significant
      trend (P = 0.065). Multivariate analysis of variance (ANOVA) showed significant
      differences both among subjects (P < 0.001) and after exposure (P < 0.001).
      Adrenaline, noradrenaline and dopamine values were not significantly different
      after exposure to noise (P > 0.05). Urinary magnesium levels were significantly
      different across time (P = 0.017). Urinary calcium levels were not significantly
      different across time (P = 0.36). Urinary phosphate values were increased after
      exposure to noise (P = 0.007); urinary creatinine was not changed after exposure
      (P > 0.05). Our study shows that noise induces significant increases of serum
      calcium and magnesium, with a borderline increase of serum phosphorus; this in
      turn is reflected in a significantly increased urinary excretion of magnesium and
      phosphate after exposure, which lasts for the following 2 days. Urinary calcium
      and creatinine were not modified by noise. The difference in catecholamine values
      did not reach statistical significance. Thus, we failed to substantiate a
      significant correlation between catecholamine secretion and magnesium metabolism,
      as others had suggested.

PMID- 11235830
TI  - Back pain in pre-registration house officers.
AB  - Back pain is a major burden on the working population. It is a particular problem
      amongst hospital staff, especially nurses. It has been poorly studied amongst
      doctors. Pre-registration house officers (PRHOs) starting their careers are
      exposed to a number of risk factors for back problems, both physical and
      psychological. This questionnaire-based study investigated the prevalence of back
      pain and its impact on the work of new graduates from two UK medical schools.
      Around half of the newly qualified PRHOs had significant back pain, one-quarter
      at least once a week. The frequency of back pain doubled once they started work,
      although the overall prevalence remained static. One in 10 of them had been
      unable to perform their normal work activities at some stage because of back
      pain. One in eight had sought professional help for back problems in the previous
      5 years. Fewer than 50% of newly qualified doctors could recall any formal
      training in lifting and handling.

PMID- 11235831
TI  - Microwave sickness: a reappraisal.
AB  - Microwave sickness (MWS) has been a disputed condition. The syndrome involves the
      nervous system and includes fatigue, headaches, dysaesthesia and various
      autonomic effects in radiofrequency radiation workers. This paper describes the
      early reports of the syndrome from Eastern Europe and notes the scepticism
      expressed about them in the West, before considering comprehensive recent reports
      by Western specialists and a possible neurological basis for the condition. It is
      concluded that MWS is a medical entity which should be recognized as a possible
      risk for radiofrequency radiation workers.

PMID- 11235832
TI  - Editorial, Vol. 50 No. 5.

PMID- 11235833
TI  - Veterans of old wars and recent conflicts in The Netherlands: their long-term
      psychological adjustment.

PMID- 11235834
TI  - Need for cognition and cognitive performance from a cross-cultural perspective:
      examples of academic success and solving anagrams.
AB  - The cross-cultural validity of the Need for Cognition Scale and its relationship
      with cognitive performance were investigated in two studies. In the first study,
      the relationships between the scale and university entrance scores, course
      grades, study skills, and social desirability were examined. Using the short form
      of the Turkish version of the Need for Cognition Scale (S. Guloz & C. J.
      Sadowski, 1995) no correlation with academic performance was found but there was
      significant correlation with a study skills scale and a social desirability scale
      created for this study. When regression analysis was used to predict grade point
      average, the Need for Cognition Scale was a significant predictor. In the second
      study, participants low or high in need for cognition solved multiple-solution
      anagrams. The instructions preceding the task set the participants' expectations
      regarding task difficulty. An interaction between expectation and need for
      cognition indicated that participants with low need for cognition performed worse
      when they expected difficult problems. Results of the two studies showed that
      need for cognition has cross-cultural validity and that its effect on cognitive
      performance was mediated by other variables.

PMID- 11235835
TI  - Loneliness and social dissatisfaction in Turkish adolescents.
AB  - The present study is an investigation of the relationships of sociometric status,
      gender, and academic achievement to loneliness levels of Turkish adolescents.
      Participants were 370 secondary school students (186 girls and 184 boys). Data on
      loneliness and social dissatisfaction levels of students were collected with the
      Turkish version of S. R. Asher and V. A. Wheeler's (1985) Loneliness and Social
      Dissatisfaction Scale. Sociometric data were gathered by using a rating scale and
      a positive nomination measure devised by S. R. Asher and K. A. Dodge (1986) in
      which participants were classified into one of four groups (popular, rejected,
      neglected, and controversial). The scores obtained from these measures were
      treated by a method similar to that of J. D. Coie, K. A. Dodge, and H.
      Coppotelli's (1982) standard score approach. Results revealed that sociometric
      status was significantly related to loneliness and social dissatisfaction as a
      function of peer relations. Members of the rejected group reported significantly
      higher levels of loneliness and social dissatisfaction than did members of the
      controversial, popular, and neglected groups. The controversial group was also
      significantly different from the popular group in loneliness level. No
      significant gender differences were found. Results also revealed a significant
      negative relationship between achievement scores and loneliness, indicating that
      as the level of loneliness increased, academic achievement decreased.

PMID- 11235836
TI  - The phenomenology of the alone condition: more evidence for the role of aloneness
      in social facilitation.

PMID- 11235837
TI  - A meta-analysis of the published research on the effects of child sexual abuse.
AB  - A meta-analysis of the published research on the effects of child sexual abuse
      (CSA) was undertaken for 6 outcomes: posttraumatic stress disorder (PTSD),
      depression, suicide, sexual promiscuity, victim-perpetrator cycle, and poor
      academic performance. Thirty-seven studies published between 1981 and 1995
      involving 25,367 people were included. Many of the studies were published in 1994
      (24; 65%), and most were done in the United States (22; 59%). All six dependent
      variables were coded, and effect sizes (d) were computed for each outcome.
      Average unweighted and weighted ds for each of the respective outcome variables
      were .50 and .40 for PTSD, .63 and .44 for depression, .64 and .44 for suicide,
      .59 and .29 for sexual promiscuity, .41 and .16 for victim-perpetrator cycle, and
      .24 and .19 for academic performance. A file drawer analysis indicated that 277
      studies with null ds would be required to negate the present findings. The
      analyses provide clear evidence confirming the link between CSA and subsequent
      negative short- and long-term effects on development. There were no statistically
      significant differences on ds when various potentially mediating variables such
      as gender, socioeconomic status, type of abuse, age when abused, relationship to
      perpetrator, and number of abuse incidents were assessed. The results of the
      present meta-analysis support the multifaceted model of traumatization rather
      than a specific sexual abuse syndrome of CSA.

PMID- 11235838
TI  - Attachment disorders: review and current status.
AB  - Developmental research on attachment has flourished in the past 15 years (C. H.
      Zeanah, 1996). However, there has been relatively scant empirical investigation
      of disorders in attachment. In this article, the pertinent developmental research
      on the attachment cycle is delineated and the current status of disordered
      attachment is examined. A particular focus is given to the conceptualization of
      the most severe form of disordered attachment, Reactive Attachment Disorder.

PMID- 11235839
TI  - Goal orientations and the search for confirmatory affect.
AB  - People differ with respect to their beliefs about the consequences of attaining
      goals. Some people (linkers) believe that attaining certain goals will make them
      happy, whereas others (nonlinkers) see their happiness as more contingent upon
      the inherent quality of their actions than upon the outcomes of those actions.
      Because of the importance linkers place on goal attainment, linkers should be
      likely to seek information indicative of their progress toward their goals.
      Because of the importance nonlinkers place on enjoyment, nonlinkers should be
      likely to seek information indicative of the pleasurableness of their current
      task. Because negative affect can signal a lack of goal progress, whereas
      positive affect can signal task enjoyment, linkers may place more weight on their
      negative than their positive affect, whereas nonlinkers may do the opposite.
      Consistent with these hypotheses, the results of this study showed that linkers
      reported more negative affect when exposed to sad videos than when exposed to
      happy videos but did not report different amounts of positive affect. Nonlinkers,
      on the other hand, reported more positive affect when exposed to happy videos
      than when exposed to sad videos but did not report different amounts of negative
      affect. The implications of this pattern for a number of theoretical perspectives
      on goals and affect are discussed.

PMID- 11235840
TI  - Journal reprints as dissemination of psychological research: courtesy,
      obligation, or obsolescence?
AB  - The proliferation of journals and the escalation of journal prices have made it
      difficult for psychologists, especially those in rural areas without access to
      comprehensive libraries, to obtain journal articles. A traditional source of
      otherwise unavailable papers is to request a reprint directly from the author.
      Although previous researchers found this method to be 60%-80% successful, there
      have been major changes in journal operations and alternative media since this
      research was conducted. In the present study, reprints were requested from 473
      corresponding authors from 10 American Psychological Association journals. The
      compliance rate was 84% and reprints took, on average, 32 days to arrive. There
      was no difference in the rate or in the speed of response due to the requestor's
      status as an academic or applied psychologist. Although functional, the
      traditional reprint request method was slow, uncertain, and costly. It is
      suggested that a demand still exists for reprints, but that electronic reprints
      should replace the traditional paper format. Key words: reprints, scientific
      communication

PMID- 11235841
TI  - Separation-individuation in late adolescence: an investigation of gender and
      ethnic differences.
AB  - Gender and ethnic differences in separation-individuation were assessed in a
      sample of 125 male and 175 female undergraduates (M age = 19.56, SD = 1.29) self
      identified as White, African American, Hispanic, or Asian. Measures used included
      a demographic questionnaire and the Separation-Individuation Test of Adolescence
      (SITA; J. B. Levine, C. J. Green, & T. Millon, 1986; J. B. Levine & S. Saintogne,
      1993). Except for results showing a greater tendency among the men to shun
      dependent ties and a superior capacity for forming close peer attachments among
      the women, separation-individuation development tended to be indistinguishable
      between the genders. Additional findings suggest that (a) Hispanics, Asians, and
      African Americans are more concerned with engulfment fears and needs for
      nurturance than Whites are; (b) Asians are more apt to shun dependent ties than
      Whites are; and (c) compared with Whites, African Americans anticipate rejection
      more and are less adept at forming close attachments with teachers.

PMID- 11235842
TI  - General relations among drug use, alcohol use, and major indexes of
      psychopathology.
AB  - Relations among measures of trait anxiety, depression, panic, somatization,
      alcohol use, drug use, and treatment for depression were investigated because,
      typically, studies (a) addressed relations among subsets of only 2 or 3 of the
      measures and (b) dealt almost exclusively with narrow samples of the population
      representing extremes on 1 or 2 of the measures. In this study, relations among
      all 7 measures were assessed with participants representing a wide range of
      scores on all the measures. The 369 participants (155 men, 214 women) were
      sampled from the general population. Three replications of the same study
      consistently yielded hypothesized positive intercorrelations among all 7 scales.
      Factor 1 (Anxiety-Depression) included Trait Anxiety, Depression, and Panic
      scales. Factor 2 (Substance Abuse) included Drug Use, Alcohol Use, Treatment for
      Depression, and Somatization scales. Factor 2 highlighted self-medication as a
      defining characteristic of somatizers and corroborated findings showing that
      substance abuse is often a precursor to treatment for depression-like symptoms
      that can be ameliorated with abstinence. Factors 1 and 2 were significantly
      intercorrelated (r = .41, df = 367, p < .05), showing a 17% shared variance in
      two common groupings of psychological dysfunction (anxiety-depression, substance
      abuse) in the general population. Thus, depending on socioeconomic and
      demographic variables, a third common form of dysfunction in the general
      population is represented by a combination of anxiety-depression plus substance
      abuse.

PMID- 11235843
TI  - Communication and consistency: AIDS talk and AIDS attitudes.
AB  - The main hypothesis tested in this study is that the frequency of talk about a
      particular domain is related to the consistency of attitudes in that domain. This
      hypothesis was developed by viewing talk as one of the ways in which people
      express their identities and by exploring the interpersonal processes involved in
      the construction of consistency. The hypothesis was tested with a questionnaire
      completed by 73 students at Oxford University. The first part of the
      questionnaire consisted of items related to attitude, and the second part
      contained questions about respondents' conversations about AIDS and related
      topics. Strong support was found for the hypothesis relating frequency of talk
      with consistency of attitudes. Data about who the respondents talked to about
      AIDS and the perceived agreement between them and their discussion partners
      demonstrated the homogeneity of the discussion environment. The implications for
      understanding attitude formation and change in everyday social contexts are
      considered.

PMID- 11235844
TI  - Stress radionuclide imaging versus stress echocardiography: a framework for
      comparisons.
AB  - Comparisons of stress-imaging procedures require analyses based on their 2
      principal applications: diagnostic and prognostic assessments. Besides comparing
      results reported in the literature--in which differences have been reported in
      the ability of stress nuclear versus stress echocardiographic imaging to predict
      a low risk of cardiac events-other factors often not reported may be important in
      discerning the relative efficacy of these tests. These include consideration of
      how these tests perform in specific, individualized patient scenarios; the effect
      of on-going technical advances on test usefulness; and evaluation of test
      worthiness according to such factors as cost-effectiveness and the magnitude of
      incremental test information that is provided. Furthermore, it is important to
      distinguish between a test's efficacy (ie, its intrinsic accuracy) and its
      effectiveness (ie, how it performs in the real world of clinical practice).

PMID- 11235845
TI  - Principal uses of myocardial perfusion scintigraphy in the management of patients
      with known or suspected coronary artery disease.
AB  - The use of myocardial perfusion single photon emission computed tomography
      (SPECT) has undergone considerable expansion and evolution over the past 2
      decades. Although myocardial perfusion imaging was first conceived as a
      noninvasive diagnostic tool for determining the presence or absence of coronary
      artery disease, its prognostic value is now well established. Thus,
      identification of patients at risk for future cardiac events has become a primary
      objective in the noninvasive evaluation of patients with chest pain syndromes and
      among patients with known coronary artery disease. In particular, the ability of
      myocardial perfusion SPECT to identify patients at low (< 1%), intermediate (1%
      to 5%) or high (> 5%) risk for future cardiac events is essential to patient
      management decisions. Moreover, previous studies have conclusively shown the
      incremental prognostic value of myocardial perfusion SPECT over clinical and
      treadmill exercise data in predicting future cardiac events. This report
      addresses the current role and new developments, with respect to the use of
      myocardial perfusion imaging, in determining patient risk for cardiac events and
      the cost-effective integration of such information into patient management
      decisions.

PMID- 11235846
TI  - Stress echocardiography: technical considerations.
AB  - Stress echocardiography has evolved into a widely practiced and accepted method
      for the noninvasive assessment of the status of the coronary anatomy.
      Furthermore, this modality incorporates the ability to assess left ventricular
      function, valvular structure and function, intracardiac masses, the pericardium,
      and hemodynamics. The extent to which this tool can reliably provide useful
      clinical information is dependent, in part, on optimal performance. The purpose
      of this report is to provide an overview of those technical considerations that
      can contribute to the successful operation of a stress echocardiography
      laboratory. Consideration is given to personnel qualifications, functional
      requirements of the digital acquisition/storage/replay system, functional
      integration of the various hardware components, characteristics of the software,
      physical layout of the facility, and alternatives to treadmill exercise as the
      stressor. A thorough understanding of the physiologic basis of stress
      echocardiography, coupled with optimization of resources used in its performance,
      enable this tool to be an extraordinarily useful and cost-efficient method for
      comprehensive cardiovascular assessment.

PMID- 11235847
TI  - Overview of stress echocardiography: uses, advantages, and limitations.
AB  - Responses of the heart to changes in our environment are probably even more
      important than how the heart functions at rest. Accordingly, stress testing with
      noninvasive imaging has become important for diagnosis, prognosis, and monitoring
      the effects of therapy. Echocardiography at rest and with stress permits
      characterization of global and segmental left ventricular function as well as
      valvular structure and function. Moreover, echocardiography can be performed
      during or after a number of different physical or even mental stressors.
      Advantages of stress echocardiography include its ready availability, relatively
      low capital cost, and incremental value in that it allows characterization of
      cardiac anatomy as well as the myocardial response to a potentially ischemic
      stimulus. Moreover, echocardiography has the potential to image myocardial
      perfusion along with wall motion and wall thickening. Substantial literature has
      now been accumulated on the value of stress echocardiography for the diagnosis of
      ischemic disease, preoperative risk assessment, and assessment of myocardial
      viability. Echocardiography has compared generally well with nuclear imaging
      techniques for the detection of angiographic coronary artery disease. Overall
      sensitivity, however, has been slightly less, particularly for the detection of
      single-vessel coronary disease, although specificity has been on average somewhat
      higher than nuclear cardiology techniques. Because of the potential for
      variability in study acquisition as well as interpretation, careful safeguards
      need to be employed. Specifically, meticulous technique needs to be applied to
      obtain high-quality images and to assure that those images are obtained promptly
      after treadmill exercise stress. Only readers with specific interest and
      expertise should interpret stress echocardiography studies. Continuing efforts
      need to be made to assess and minimize variability and to assure continuing
      quality improvement. Advances in instrumentation, including evolving technology
      for real-time 3-dimensional imaging, and echocardiography contrast assessment of
      myocardial perfusion will likely improve the sensitivity of echocardiography and
      further extend its usefulness.

PMID- 11235848
TI  - Postexercise left ventricular function: a comparative assessment by different
      noninvasive imaging modalities.
AB  - The variety of noninvasive imaging modalities now available permits assessment of
      different aspects of left ventricular function in the postexercise state. Some of
      these modalities, such as first-pass radionuclide ventriculography, permit a
      nearly instantaneous assessment of left ventricular function in the early
      postexercise state. These modalities indicate that most exercise-induced left
      ventricular wall motion abnormalities resolve quickly after exercise. Resting
      wall motion abnormalities may also improve in the postexercise period; this
      response indicates the presence of hibernating myocardium capable of improving in
      response to myocardial revascularization procedures. On the other hand, all
      imaging techniques indicate that a certain percentage of exercise-induced wall
      motion abnormalities may persist into the postexercise period, and this finding
      signifies that severe coronary disease subtends the region of persisting wall
      motion abnormality. Further, if there is increased left ventricular size after
      exercise, both extensive and severe coronary disease are present. A conceptual
      framework for unifying these disparate findings is provided. These results
      underscore the importance of postexercise imaging in enhancing clinical
      assessment and imply that there are important technical considerations to
      contemplate when performing certain tests such as postexercise echocardiography.

PMID- 11235849
TI  - Echocardiographic assessment of viable myocardium.
AB  - Left ventricular function is one of the most important determinates of long-term
      prognosis in patients with coronary artery disease. In recent years, it has
      become apparent that left ventricular dysfunction in patients with coronary
      artery disease is not always an irreversible process stemming from myocardial
      necrosis and fibrosis. Myocardial tissue can undergo both a state of potential
      reversible dysfunction because of prolonged sustained ischemia (hibernating
      myocardium) or episodes of acute ischemia (stunned myocardium). Revascularization
      of this tissue may improve regional and global left ventricular function and
      therefore prognosis. Numerous studies have now firmly established dobutamine
      echocardiography as a safe, reliable, and accurate imaging modality in the
      assessment of reversible left ventricular dysfunction. Furthermore, dobutamine
      echocardiography has been shown to have good sensitivity, specificity, and, more
      importantly, positive predictive accuracy in identifying both acute and chronic
      reversible left ventricular dysfunction for risk satisfaction and prognosis.

PMID- 11235850
TI  - Principles for combining radionuclide and echocardiographic stress imaging into a
      single clinical laboratory service.
AB  - Physicians who supervise stress-imaging procedures, whether they be stress
      nuclear or stress echocardiography tests, are increasingly required to
      incorporate important principles in the interpretation of the test results.
      Important guiding principles, common to these tests, are reviewed in this
      article. The principles include the following: avoiding categorical
      interpretation of test results; identifying equivocal test responses; combining
      diagnostic and prognostic information in rendering information to referring
      physicians; integrating the stress test results with other clinical data and
      using Bayesian analysis as a decision-aid; reporting one's confidence in the
      interpretation of the results of testing; characterizing both the extent and
      severity of any induced myocardial ischemia; and analyzing the test results in a
      blinded fashion, without prior knowledge of patient clinical history

PMID- 11235851
TI  - Women's dreams reported during first pregnancy.
AB  - This study analysed women's dreams reported during first pregnancy, a subject
      matter located at the crossroads of the psychology of dreams and the psychology
      of pregnancy. In the comparison of dreams reported by first-time pregnant women,
      to those reported by controls, we hypothesized that pregnant women's dreams
      would: (i) include more pregnancy-related content; (ii) display a higher degree
      of anxiety; and (iii) rate higher on a primary-process thinking (PPT) scale. As
      predicted, it was found that pregnancy-related contents significantly occupied
      pregnant women's dreams, a fact that might be attributed to an attempt to process
      and master the experience. Contrary to our expectations, it was found that
      anxiety and PPT were not significantly higher among pregnant women. An attempt to
      account for these findings raised methodological, as well as theoretical issues,
      consequently leading to a re-examination of the original hypotheses. Thus, it was
      claimed that the linkage of pregnancy to increased anxiety and PPT is grossly
      unbalanced.

PMID- 11235852
TI  - Prevalence of Alzheimer's disease, vascular dementia and dementia with Lewy
      bodies in a Japanese population.
AB  - We studied the prevalence of dementing disorders in a rural town of Japan (Amino
      cho), using a door-to-door two-phase design. Of the 170 persons screened as
      having cognitive impairment, 142 cases were diagnosed as having dementia. The
      prevalence (cases/100 aged 65 years older) was 3.8 for all types of dementia, 2.1
      for Alzheimer's disease (AD), 1.0 for vascular dementia (VD) and 0.7 for other
      types of dementia. Among other types of dementia, there were four male patients
      with dementia with Lewy bodies (prevalence: 0.1), but no patients with
      frontotemporal lobar degeneration. The overall prevalence was higher in women for
      AD, while that of VD was the same in both sexes. With results similar to many
      previous studies in Western countries and some recent surveys in Japan, the
      present sudy clearly showed that AD is more prevalent than VD.

PMID- 11235853
TI  - Open study of effects of alprazolam on seasonal affective disorder.
AB  - Seasonal affective disorder (SAD) differs from depression with melancholic
      features in atypical symptoms, such as hyperphagia, hypersomnia and weight gain.
      Moreover, SAD is confined to a certain season of the year. We examined the
      pharmacological efficacy of alprazolam for treatment of patients with SAD. Six
      patients with SAD were treated with alprazolam at doses of 1.2 mg/day or 1.2
      mg/day first and then 2.4 mg/day for 2 weeks. The improvement was evaluated by
      the change of total score of the SIGH-SAD (with both 21 items HAMD and eight
      items atypical symptoms) and the clinical global impression (CGI). Although only
      two patients showed a remarkable improvement by SIGH-SAD, all patients showed a
      higher than moderate improvement with CGI. Our findings suggest that alprazolam
      might be efficacious for certain SAD patients.

PMID- 11235854
TI  - Research on psychosomatic complaints by senior high school students in Tokyo and
      their related factors.
AB  - The purpose of this study was to clarify the relationships between psychosomatic
      complaints of senior high school students in Tokyo and the cognition they receive
      from their fathers, mothers, friends, teachers, and schoolwork and between their
      complaints and lifestyle habits. The subjects were 168 first-grade students (58
      males and 110 females) at a Tokyo Metropolitan senior high school. In June 1996,
      a collective survey was carried out, using questionnaires. Moreover, I conducted
      a longitudinal study to investigate the variation of their complaints over the 3
      years at the school. The females had more psychosomatic complaints than the
      males. There was the relationship between their psychosomatic complaints and the
      cognition they receive from their fathers, mothers and teachers, the relationship
      between their psychosomatic complaints and their schoolwork, the relationship
      between their psychosomatic complaints and their ingestion conditions at meals,
      or sleeping hours. As for the their complaints, they had more complaints at
      admission than at the completion of their first grade and at graduation.

PMID- 11235855
TI  - Reliability and validity of Kasahara's scale of melancholic type of personality
      (Typus melancholicus) in a German sample population.
AB  - We explored the reliability and validity of Kasahara's scale of melancholic type
      of personality (KMT) in a German sample population. Subjects comprised 66
      patients diagnosed with an affective disorder (F3, ICD-10) and 94 controls.
      Concerning reliability, KMT scores showed internal consistency with Cronbach's
      alpha coefficients of 0.65 for patients and 0.67 for controls. The KMT items,
      except for number 13 in controls, showed significant item-total correlations. In
      a test-retest procedure, the KMT total score and individual item scores were
      statistically similar and correlated. These results indicate reliability of the
      KMT. Concerning validity, KMT scores were significantly higher in patients than
      in controls. By controlling the effects of age and sex, partial correlation
      coefficients in a comparison of KMT and Zerssen's F-List (F-List) scores were
      0.40 in patients and 0.53 in controls. These results show both the constructive
      and concurrent validity of the KMT. Sufficient reliability and validity of the
      KMT were shown in this German sample population to encourage cross-cultural
      investigation of Typus melancholicus.

PMID- 11235856
TI  - Haplotype analyses with the human leucocyte antigen and tumour necrosis factor
      alpha genes in narcolepsy families.
AB  - Our previous study suggested that the tumour necrosis factor-alpha gene with
      thymine residue at position -857 in its promoter region [TNF-alpha(-857T)] could
      be associated with human narcolepsy independently of a strong association of the
      human leucocyte antigen (HLA)-DRB1*1501 with the disorder. To understand the
      relationship of DRB1*1501 with TNF-alpha(-857T) in narcoleptic patients, we
      investigated 28 members of four Japanese narcolepsy families and determined the
      haplotypes with the HLA-B, TNF-alpha(-857C/T) and HLA-DRB1 in the members. The
      resultant haplotypes indicated that not only the DRB1*1501-TNF-alpha(-857C)
      haplotype but also the DRB1*1501-TNF-alpha(-857T) haplotype, which is rare in
      healthy individuals and may have a strong predisposition to the disorder, were
      present in the affected members. From the chromosomal recombination observed in a
      few members, it is possible that chromosomal recombination could play a role in
      the generation of the rare DRB1*1501-TNF-alpha(-857T) haplotype.

PMID- 11235857
TI  - Ten year progressive ventricular enlargement in schizophrenia: an MRI
      morphometrical study.
AB  - Recent studies of the brain using magnetic resonance imaging (MRI) have suggested
      progressive structural changes in schizophrenics. However, those studies were
      conducted over periods of less than 5 years and thus lacked sufficient capacity
      to determine the course and nature of this process. In this study, MRI scans were
      obtained in 15 schizophrenics and 12 controls at baseline and after 4- and 10
      year follow ups. Volumes of the lateral ventricles were measured. Patients were
      assessed by the Brief Psychiatric Rating Scale (BPRS) at the same two time
      points: at baseline and at 10-year follow up. After 10 years, a significant
      lateral ventricular enlargement was found in patients (mean percentage change:
      +22.9%) but not in controls (5.1%). Although our results are not in disagreement
      with the neurodevelopmental hypothesis, they do provide strong evidence that in
      schizophrenia progressive brain reduction occurs even in its chronic stage.

PMID- 11235858
TI  - Sylvian fissure and medial temporal lobe structures in patients with
      schizophrenia: a magnetic resonance imaging study.
AB  - Volumes of the medial temporal lobe structures (i.e. the amygdala, hippocampus,
      and parahippocampal gyrus), Sylvian fissure, and inferior horn of the lateral
      ventricle relative to the cerebral hemisphere were measured in 24 patients with
      schizophrenia and 23 normal controls using magnetic resonance imaging. The
      patients had significantly larger Sylvian fissures and inferior horns bilaterally
      than the controls. In the patients the right Sylvian fissure size showed a
      significant positive correlation with the duration of illness. Moreover, earlier
      onset of illness was significantly correlated with decreased volume of the left
      medial temporal lobe structures. These results replicate previous finding of
      inferior horn enlargement and suggest the significance of the Sylvian fissure and
      the medial temporal lobe structures in pathophysiology of schizophrenia.

PMID- 11235859
TI  - Absence of sleep spindles in human medial and basal temporal lobes.
AB  - All-night recordings from subdural electrocorticographic (ECoG) electrodes on the
      human medial and basal temporal lobes were analysed to examine spindling
      activities during sleep. Subjects were three males and three females who were
      candidates for neurosurgical treatments of partial epilepsy. Subdural electrodes
      were attached to the medial and basal temporal lobe cortices, allowing ECoG and
      electroencephalogram from the scalp vertex (Cz EEG) to be recorded simultaneously
      during all night sleep. In one case, subdural electrodes were attached also on
      the parietal lobe. Fast Fourier transformation (FFT) analyses were performed on
      the ECoG and Cz EEG signals. No organized sleep spindles or sigma band (12-16 Hz)
      peaks in FFT power spectra were observed from the medial or basal temporal lobes
      of the non-epileptogenic hemispheres during non-rapid eye movement (NREM) sleep.
      In a case with parietal electrodes, organized spindle bursts were observed in
      parietal signals synchronized with Cz spindles. Although delta band (0.3-3 Hz)
      power from both the medial and basal temporal lobes fluctuated across each night
      as expected, sigma activity changed little. However, 14 Hz oscillatory bursts
      were observed in the medial basal temporal lobe of epileptogenic hemisphere in
      two cases and bilaterally in one case during not only NREM sleep but rapid eye
      movement (REM) sleep and wakefulness. From the present study we conclude that
      sleep spindle activities are absent in the medial and basal temporal lobes.
      Fourteen Hz oscillatory bursts observed from the medial or basal temporal lobe in
      some cases were not considered to be sleep spindles since they also appeared
      during REM sleep and wakefulness. These waveforms could have originated due to
      epileptic pathology, since they frequently appeared in epileptic regions.

PMID- 11235860
TI  - Course and outcome of bipolar II disorder: a retrospective study.
AB  - To study course and outcome of Bipolar II disorder, 217 major depressive episode
      (MDE) patients were interviewed with Structured Clinical Interview for DSM-IV.
      Patients with more than three MDE and patients with fewer MDE were compared.
      Patients with more than three MDE were 77.8%. Comparisons, controlled for
      confounding effects of age and illness duration, found that patients with many
      MDE had significantly lower age at onset and more chronicity. Results support
      subtyping of Bipolar II in a small good-outcome group, and a large moderate-poor
      outcome group.

PMID- 11235861
TI  - Early sexual abuse and low cortisol.
AB  - Post-traumatic stress disorder (PTSD) is a mental health disorder precipitated by
      a stressful event that produces fear or terror in the individual. Post-traumatic
      stress disorder studies, particularly in early sexual abuse, have been associated
      with neuroendocrine dysfunction, most notably the hypothalamic-pituitary-adrenal
      (HPA) axis. Since the literature on PTSD and neuroendocrine factors in young
      subjects has been sparse, the present studies were designed to look at the basal
      functioning of the HPA axis in response to early sexual abuse in girls aged 5 to
      7 years. Morning salivary samples were collected for cortisol determination from
      subjects and controls who were scheduled for a physical exam by their
      pediatrician. The present study shows that subjects who had been abused within
      the last couple of months had significantly lower cortisol in comparison to
      control subjects (age, social economic status and race matched). The data suggest
      that children may have an impaired HPA axis after early trauma.

PMID- 11235862
TI  - Electroconvulsive shock regulates serotonin transporter mRNA expression in rat
      raphe nucleus.
AB  - The antidepressive actions of electroconvulsive shock (ECS) therapy are
      considered to involve altered neurotransmission of serotonin. In this study, we
      investigated the effects of acute and chronic ECS on 5-hydroxytryptamine (5-HT)
      transporter mRNA expression in rat raphe nucleus. We found that serotonin
      transporter (5-HTT) mRNA expression was decreased in 9 and 24 h after acute ECS
      and in 3, 9, 24 h and 2 weeks after chronic ECS in rat raphe nucleus. We presume
      that the adaptive change in 5-HTT mRNA expression is possibly related to the
      therapeutic efficacy of electroconvulsive therapy (ECT) on medication-resistant
      depression.

PMID- 11235863
TI  - Restlessness related to SSRI withdrawal.
AB  - There are reports that abrupt withdrawal of various selective serotonin re-uptake
      inhibitors, such as fluvoxamine, can elicit in patients various withdrawal
      symptoms. Fluvoxamine has been widely used in Japan for approximately 1 year.
      However, there have been no case reports of withdrawal symptoms following abrupt
      fluvoxamine discontinuation in Japan. The author reports a case where the abrupt
      discontinuation of fluvoxamine produced restlessness in a depressed patient. The
      restlessness disappeared soon after the reinstatement of treatment with
      fluvoxamine. This case report suggests that clinicians should carefully
      scrutinize a patient's compliance to fluvoxamine as the withdrawal symptoms
      observed following abrupt discontinuation might be regarded as a relapse of
      depression or side-effects of the medicine.

PMID- 11235864
TI  - Restlessness in suboccipital muscles as a manifestation of akathisia.
AB  - Antipsychotic-induced akathisia is primarily manifested as restlessness,
      particularly expressed in the legs. Consequently, rating scales and the research
      criteria of DSM-IV regard restlessness in the legs as the major sign of
      akathisia, although it has been suggested that such restlessness may occur in
      other areas of the body. A case of antipsychotic-induced akathisia is reported
      where the region of inner restlessness (the subjective component) was identified
      in posterior cervical muscles. The patient was initially suspected to be
      experiencing somatic delusions and the dose of antipsychotic medication was
      increased. This did not improve the symptoms, and upon careful questioning about
      his head discomfort, the patient acknowledged that he felt an inner restlessness
      in the suboccipital muscles. The restlessness ceased with intramuscular biperiden
      and subsequent discontinuation of antipsychotic medication. This case suggests
      that subjective restlessness may occur in muscle groups that are not usually
      associated with akathisia. Thus, this report may assist clinicians in the
      diagnosis of akathisia that could be overlooked or misdiagnosed as somatic
      delusions or the worsening of the patient's psychosis.

PMID- 11235865
TI  - Direct and indirect inactivation of Microcystis aeruginosa by UV-radiation.
AB  - Excessive algal growth in drinking water sources like lakes and reservoirs is
      responsible for filter-clogging, undesirable taste and odor, disinfection-by
      product formation and toxin generation. Although various methods are currently
      being used to control algal bloom, their successes are limited. Some water
      utilities routinely use copper sulfate to control excessive algal growth. But
      there is a growing concern against its use mainly because it is non-specific to
      target algae and kills many non-target species. In this study, the scope of using
      UV-radiation to control algal growth was assessed using Microcystis aeruginosa as
      test species. A UV-dose of 75 mW s cm(-2) was found to be lethal to M.
      aeruginosa. A smaller dose of 37 mW s cm(-2) prevented growth for about 7 days.
      It was found that UV-radiation may increase the specific gravity of the cells and
      thus may adversely affect the ability of the cells to remain in suspension. Three
      days after a UV-dose of 75 mW s cm(-2), almost all the cells settled to the
      bottom of the incubation tubes, whereas all the unirradiated cells remained in
      suspension. It was also observed that UV-radiation on algal extracellular
      products has a significant residual effect and can contribute to algal growth
      control. The extent of residual effect depends on the UV-dose and can continue
      even for 7 days. UV-radiation was found to produce H2O2 in the microM level
      concentration. But at such level, H2O2 itself is not likely to cause the residual
      effect that was found in this study.

PMID- 11235866
TI  - Aerobic and anoxic biodegradation of benzoate: stability of biodegradative
      capability under endogenous conditions.
AB  - Aromatic organic compounds are degraded by different enzyme systems under aerobic
      and anoxic conditions. This raises the question of how bacteria in biological
      nitrogen removal processes, which cycle bacteria between aerobic and anoxic
      environments, regulate their enzyme systems for degrading aromatic compounds. As
      a first step in answering that question, mixed microbial communities were grown
      on benzoate as sole carbon source in chemostats under fully aerobic and fully
      anoxic (nitrate as the electron acceptor) conditions and tested for their ability
      to degrade benzoate in batch reactors after exposure to aerobic or anoxic
      conditions in the absence of substrate. Aerobically grown biomass retained its
      ability to degrade benzoate without loss of activity after endogenous exposure to
      aerobic conditions for up to 8 h. However, when exposed to anoxic conditions, the
      biomass rapidly lost its aerobic benzoate degrading activity, retaining less than
      20% of the initial activity after 8 h. Similarly, anoxically grown biomass
      retained its ability to degrade benzoate without loss of activity after
      endogenous exposure to anoxic conditions for up to 8 h. However, when anoxically
      grown biomass was exposed to aerobic conditions, only 20% of its initial activity
      was lost in the first 2 h, after which the remaining activity was retained for up
      to 8 h. Similar experiments with pyruvate showed that the 20% loss of activity
      was not due to loss of denitrifying enzymes, suggesting that it was due to loss
      of catabolic enzymes.

PMID- 11235867
TI  - Photocatalytic degradation of trichloroethylene in water using TiO2 pellets.
AB  - A recirculating system of aqueous trichloroethylene (TCE) solutions through the
      packed bed reactor with TiO2 pellets has been developed in order to mineralize
      TCE without difficulties for filtration and recovery of catalyst. The TiO2
      pellets prepared by sol gel method have photocatalytic activity similar to
      commercially available PC-101 and PC-102 in the powder form and to ST-B11
      pellets. In batch experiments with TiO2 powders, Degussa P-25 is the most active
      photocatalyst, which indicates that specific surface area is not an important
      factor controlling the photocatalytic activity in aqueous solutions. The
      degradation rates of TCE in the recirculating system with TiO2 pellets decreased
      in the presence of H2O2, while were remarkably accelerated by adding S2O8(2-).
      The presence of S2O8(2-) ions more than 0.01 mol dm(-3) completely suppressed
      hole-electron recombination and mineralized 50 ppm TCE with the 2 h irradiation.
      In a reactor without TiO2 photocatalysts, TCE was photodegraded by SO4- radicals
      which produced by photodissociation of S2O8(2-). The degradation rates increased
      with increase of the initial S2O8(2-) concentration. However, TCE was not
      mineralized but converted to intermediates which were slowly degraded to Cl- by
      continuing the irradiation.

PMID- 11235868
TI  - Effect of sludge fasting/feasting on growth of activated sludge cultures.
AB  - Reduction of excess sludge in an oxic-settling-anoxic (OSA) activated sludge
      process might be attributed to a "sludge fasting (insufficient food under an
      anoxic condition)/feasting (sufficient food under an oxic condition)" treatment.
      This paper was to examine this explanation by investigating both the sludge
      fasting/feasting phenomenon and the effect of a fasting/feasting treatment on
      sludge growth. In this study, five different activated sludge cultures cultivated
      using synthetic wastewater composed of mainly glucose and other necessary
      nutrients: (1) an aerobic batch culture, (2) an intermittently aerated batch
      culture, (3) an anoxic batch culture, (4) a continuous aerobic culture, and (5)
      an OSA culture, were employed. It was found that only the aerobic batch culture
      and the aerobic continuous culture are fastable when the oxidation reduction
      potential (ORP) level is below 100 mV under no-food condition during a 2-h
      fasting treatment, showing that both the biomass and carbohydrate storage of
      these two cultures were reduced after the treatment. When the fasted cultures
      were treated in a feasting environment, an accumulation of carbohydrate storage
      did not occur, while specific oxygen uptake rates (SOUR) showed a sharp increase.
      Both the substrate utilization and biomass growth rates were also accelerated. It
      was therefore confirmed that a sludge feasting did occur after a fasting
      treatment for the fastable cultures. However, an increase in sludge ATP content
      was not brought about by the feasting treatment. The sludge fasting/feasting
      treatment in this paper could not induce a reduction of the observed growth yield
      (Y(obs)) in all the cultures cultivated with glucose-based synthetic wastewater.

PMID- 11235869
TI  - Observations on changes in ultrasonically treated waste-activated sludge.
AB  - This work experimentally elucidates the effects of ultrasonic treatment on the
      physical, chemical, and biological characteristics of a waste-activated sludge. A
      critical ultrasonic power level exists above which, accompanied with the release
      of divalent cations from the sludge body, the floc structure effectively
      disintegrated, microbial level acceptably disinfected, and particulate organic
      compounds sufficiently transformed into soluble state. Both ultrasonic vibration
      and bulk temperature rise contribute to the treatment efficiency. Possible
      mechanisms of ultrasonic treatment are discussed.

PMID- 11235871
TI  - The roles of calcium in sludge granulation during UASB reactor start-up.
AB  - Six upflow anaerobic sludge blanket (UASB) reactors were concurrently operated
      for 146 d to examine the effects of calcium on the sludge granulation process
      during start-up. Introduction of Ca2+ at concentrations from 150 to 300 mg/l
      enhanced the biomass accumulation and granulation process. The calcium
      concentration in the granules was nearly proportional to the calcium
      concentration in the feed, and calcium carbonate was the main calcium precipitate
      in the granules. The specific activity of granules decreased with increasing
      influent calcium concentration. The optimum calcium concentration for the
      granulation was from 150 to 300 mg/l. The addition of low-concentration calcium
      to the UASB reactors appeared to enhance the three steps of sludge granulation:
      adsorption, adhesion and multiplication, but it did not lead to a different
      proliferation of predominant microorganisms in the granules.

PMID- 11235870
TI  - Use of Fenton reagent to improve organic chemical biodegradability.
AB  - Fenton reagent has been used to test the degradation of different organic
      compounds (formic acid, phenol, 4-chlorophenol, 2,4-dichlorophenol and
      nitrobenzene) in aqueous solution. A stoichiometric coefficient for the Fenton
      reaction was found to be 0.5 mol of organic compound/mol of hydrogen peroxide,
      except for the formic acid where a value of approximately one was obtained (due
      to the direct formation of carbon dioxide). The treatment eliminates the toxic
      substances and increases the biodegradability of the treated water (measured as
      the ratio BOD5/COD). Biodegradability is attained when the initial compound is
      removed.

PMID- 11235872
TI  - Effect of agitation, turbidity, aluminium foil reflectors and container volume on
      the inactivation efficiency of batch-process solar disinfectors.
AB  - We report the results of experiments designed to improve the efficacy of the
      solar disinfection of drinking water, inactivation process. The effects of
      periodic agitation, covering the rear surface of the container with aluminium
      foil, container volume and turbidity on the solar inactivation kinetics of
      Escherichia coli (starting population = 10(6) CFU ml(-1)) were investigated. It
      was shown that agitation promoted the release of dissolved oxygen from water with
      subsequent decrease in the inactivation rates of E. coli. In contrast, covering
      the rear surface of the solar disinfection container with aluminium foil improved
      the inactivation efficiency of the system. The mean decay constant for bacterial
      populations in foil-backed bottles was found to be a factor of 1.85 (std. dev. =
      0.43) higher than that of non-foil-backed bottles. Inactivation rates decrease as
      turbidity increases. However, total inactivation was achievable in 300 NTU
      samples within 8 h exposure to strong sunshine. Inactivation kinetics was not
      dependent on the volume of the water container for volumes in the range 500-1500
      ml.

PMID- 11235873
TI  - Geochemical changes in sulfidic mine tailings stored under a shallow water cover.
AB  - The objective of this study was to assess the effectiveness of an engineered
      shallow water cover in reducing the oxidation of sulfidic mine tailings and thus
      preventing the development of acid rock drainage. Fresh tailings were submerged
      under a 0.3-m water cover in experimental field cells. From 1996 to 1998, we
      followed the chemistry of the interstitial water near the tailings-overlying
      water interface using in situ dialysis, and determined pH and dissolved oxygen
      (DO) profiles across the tailing water interface using micro-electrodes.
      Penetration of DO into the tailings was limited to <7 mm, even in the presence of
      DO produced by benthic periphyton. Anoxia in the tailings was further
      demonstrated by the appearance of dissolved sigmaH2S, Fe and Mn in pore water at
      depths -1.5 cm below the interface. However, there was clear evidence of surface
      oxidation of the mine tailings at the mm scale (i.e., DO depletion, coupled with
      localized increases in [H+] and [SO4(2-)]). Mobilization of Cd and Zn from this
      surface layer was indicated by the presence of sub-surface peaks in the
      concentrations of these two metals in the tailings interstitial water and by a
      change in their solid phase partitioning from refractory to more labile
      fractions. In contrast, mobilization of Cu from tailings was less evident. Unlike
      previous reports, which suggested that submerged tailings were effectively inert,
      our results show alteration of the superficial layer over time.

PMID- 11235874
TI  - Kinetics of the reaction between ozone and phenolic acids present in agro
      industrial wastewaters.
AB  - The kinetics of the ozonation of three phenolic acids is investigated from ozone
      absorption experiments in a semi-continuous reactor. After the evaluation of
      stoichiometric ratios for the individual reactions between ozone and each
      phenolic acid, the oxidation of p-hydroxybenzoic acid by ozone is performed in a
      first stage. The influence of the operating variables on the degradation process
      is established, and the application of a mass transfer with chemical reaction
      model based on the film theory leads to the determination of the reaction orders
      and kinetic rate constants. The experimental absorption rates obtained agree well
      with those calculated theoretically. In the second stage, a mixture of ferulic
      acid (4-hydroxy-3-methoxycinnamic acid), beta-resorcylic acid (2,4
      dihydroxybenzoic acid) and p-hydroxybenzoic acid is ozonated under different
      experimental conditions. The kinetic study is performed by means of a competitive
      method that takes p-hydroxybenzoic acid as reference compound. The application of
      this model allows to determine the kinetic rate constants for each compound,
      which are correlated as a function of pH and temperature. The results obtained
      support that the kinetic regime of absorption is fast and pseudo-first order with
      respect to ozone, a condition required by the competitive method used.

PMID- 11235875
TI  - Detergents in drainage systems for buildings.
AB  - Current soil waste vent (SWV) system design guides aim to produce ventilated
      drainage networks for buildings which protect attached water trap seals from
      unwanted air pressure effects. Such effects may cause trap seal failure that are
      caused by airflow induction during discharge. The ventilation design guides are
      based on steady-state experiments utilising cold clean water as a test media.
      However, most 'grey' and 'black' water sources are dosed with detergent, and are
      often warm, which significantly alters the behaviour when compared to clean
      water. Thus, current design standards provide only approximations of SWV system
      response. Results indicate that induced airflows in warm detergent-dosed water
      can be significantly higher than those measured in clean water systems, by a
      factor of more than 2. This paper quantifies the effect of detergents in SWV
      systems in terms of observed air entrainment rates and previously published
      research on the factors that contribute to air entrainment. Results of previous
      work are cast into dimensionless groupings suitable for inclusion into a
      mathematical simulation model based on a finite difference scheme. It utilises
      the method of characteristics as a solution technique to simulate drainage system
      operation via the equations that define unsteady partially filled or full bore
      pipe flows and the boundary conditions represented by water traps and other
      common system components.

PMID- 11235876
TI  - Ozonation of aqueous azo dye in a semi-batch reactor.
AB  - The ozonation of wastewater containing azo dye in a semi-batch reactor has been
      studied. Results revealed that the rate of ozone transfer increased with
      increases in the initial dye concentration, the applied ozone dose and
      temperature. A model was developed to predict the enhancement factor of ozone
      mass transfer. This model enables the prediction of mass transfer coefficient of
      ozone from the following parameters: initial dye concentration, applied ozone
      dose, temperature and concentration of dissolved ozone in the organic-free water.
      This model was also valid for reactors of larger sizes. Result of kinetic studies
      showed that ozonation of the azo dye was a pseudo-first-order reaction with
      respect to dye. The apparent rate constant increased with the applied ozone dose
      and temperature. However, the apparent rate constant declined logarithmically
      with increasing initial dye concentration. In addition, ozonation reduced
      chemical oxygen demand and enhanced the biodegradability of the wastewater.

PMID- 11235877
TI  - Effect of adding phosphate to drinking water on bacterial growth in slightly and
      highly corroded pipes.
AB  - The effect of phosphate addition in drinking water was tested under static
      conditions as batch tests and under dynamic conditions using continuously fed
      reactors. Phosphate supplements in batch tests from 0.1 to 2 mg P-PO4 L(-1) did
      not show any relationship between bacterial growth and phosphate concentration.
      Dynamic tests in slightly corroded reactor (stainless steel) treated at 1 mg P
      PO4 L(-1) showed only a moderate improvement in the growth of microorganisms. On
      the contrary, phosphate treatment applied to the highly corroded reactor (unlined
      cast iron) led to an immediate, drastic drop in iron oxide release and bacterial
      production. Phosphate uptake by the reactor wall was less than 14% with the
      stainless-steel reactor and 70-90% with the corroded cast iron reactor. Moreover,
      about 5% of the phosphate associated to corroded iron pipe walls was released for
      20 days after the end of treatment.

PMID- 11235878
TI  - Assimilable organic carbon in molecular weight fractions of natural organic
      matter.
AB  - Assimilable organic carbon (AOC) in natural organic matter (NOM) has been
      measured in three Norwegian waters. The AOC measurement has been done on
      unfiltered and membrane-filtered (molecular weight (MW) cut-off of 1000 and
      10,000) samples. While the colour in the waters is mainly related to the NOM with
      MW > 10,000, the AOC was mainly related to the NOM with MW < 1000. The fraction
      of the NOM with MW < 1000 corresponds to 16-38% of the total organic carbon
      (TOC), and 4-9% of the colour. This shows that a water treatment process removing
      the colour and a large part of the TOC in the water will not necessarily result
      in a reduction in the biofilm formation potential.

PMID- 11235879
TI  - New process for simultaneous removal of nitrogen and sulphur under anaerobic
      conditions.
AB  - A granular activated carbon (GAC) anaerobic fluidised-bed reactor treating
      vinasse from an ethanol distillery of sugar beet molasses was operated for 90
      days, the first 40 days of start-up followed by 50 days of operation at constant
      organic loading rate of 1.7g COD/Ld. The reactor showed good performance in terms
      of organic matter removal but an anomalous behaviour in terms of unusual high
      concentrations of molecular nitrogen in the biogas. The analysis of the different
      nitrogenous and sulphur compounds and the mass balances of these compounds in the
      liquid and gas phases clearly indicated an uncommon evolution of nitrogen and
      sulphur in the reactor. About 50% of the nitrogen entering the reactor as total
      Kjeldahl nitrogen (TKN) was removed from the liquid phase appearing as N2 in the
      gas phase. Simultaneously, only 20% of the S-SO4(2-) initially present in the
      influent appears as S-S2- in the effluent or S-H2S in the biogas, indicating that
      80% of the sulphur is removed. This behaviour has not been reported previously in
      the literature. These observations may suggest a new anaerobic removal process of
      ammonia and sulphate according to an uncommon mechanism involving simultaneous
      anaerobic ammonium oxidation and sulphate reduction.

PMID- 11235880
TI  - Contaminant interactions with geosorbent organic matter: insights drawn from
      polymer sciences.
AB  - This is a state-of-science review of interrelationships between the
      sorption/desorption behaviors and chemical structures of natural organic matter
      (NOM) matrices associated with soils, sediments and aquifer materials. It
      identifies similarities between these behavior-property interrelationships for
      natural geosorbents and those for synthetic organic polymers. It then invokes,
      with appropriate restrictions and modifications, several structure-function
      relationships that have been developed for synthetic polymers to explain the
      behavior of NOM matrices with respect to the sorption and desorption of
      hydrophobic organic contaminants (HOCs). Previous research regarding HOC sorption
      and desorption by different types of NOM and by synthetic polymers is summarized,
      and research requirements for further refinement of the NOM-polymer analogy are
      examined. The discussion focuses on structural and compositional heterogeneities
      that exist at the particle and aggregate scale, a scale at which homogeneity is
      commonly, and often improperly, assumed in the development of contaminant fate
      and transport models.

PMID- 11235881
TI  - A sensitive seminested PCR method for the detection of Shigella in spiked
      environmental water samples.
AB  - A rapid seminested polymerase chain reaction (PCR) method for the specific,
      sensitive detection of virulent Shigella spp. in spiked environmental water
      samples was developed. A set of primers specific for the invasion plasmid antigen
      gene (ipaH) of virulent Shigella spp. and enteroinvasive Escherichia coli
      produced a 620-bp fragment that was used as template for the seminested primer
      pair delineating a 401-bp fragment. By using agarose gel electrophoresis for
      detection of the seminested PCR-amplified products, a detection limit of 1.6 x
      10(3) cfu S. flexneri was obtained with amplification reactions from crude
      bacterial lysates. The PCR procedure coupled with an enrichment culture incubated
      for 6 h detected as few as 1.6 S. flexneri organisms in pure culture. Treated
      sewage, ground, surface and drinking water samples collected from various sources
      were seeded with S. flexneri and incubated in GN broth for 6 h before detection
      by seminested PCR. A detection limit lower than 14 cfu/ml was achieved in some
      water samples. The results indicate that the described seminested PCR has the
      advantage of a rapid turnaround time and it fulfills the requirements of
      sensitivity and specificity for use in an environmental laboratory.

PMID- 11235882
TI  - Stability of particle flocs upon addition of natural organic matter under
      quiescent conditions.
AB  - In this research, the influence of two natural organic polymers (polysaccharide
      and humic acid) on the stability of colloidal aggregates was examined. The
      primary objective of this research was to determine whether addition of organic
      matter to floc suspensions results in the fragmentation or stabilization of
      aggregates. A second objective was to determine how the size of aggregates and
      the composition of organic matter influence the floc breakup or stabilization
      process. It was found that the stability of aggregates depended on the type of
      organic material present as well as floc size. For example, humic acid increased
      the stability of aggregates more effectively than polysaccharides of larger size.
      It was also found that the addition of humic acid or polysaccharide generally
      decreased the rate of coagulation of small aggregates but had less influence on
      large aggregates. In no case did the addition of polysaccharide or humic acid
      result in the fragmentation of particle aggregates. The existence of strong
      interparticle forces within flocs prevented aggregate breakup upon adsorption of
      natural organic polymers. The results presented here provide important new
      information regarding the influence of NOM on the behavior of particles in
      aquatic systems.

PMID- 11235883
TI  - Bioaugmentation with resin-acid-degrading bacteria enhances resin acid removal in
      sequencing batch reactors treating pulp mill effluents.
AB  - Resin acids are the major toxicants in pulp and paper mill effluents (PPMEs), and
      they form pitch interfering with papermaking. Efficient and reliable resin acid
      removal is critically important to prevent toxicity discharge and ensure proper
      functioning of paper machines. Two resin-acid-degrading bacteria, Pseudomonas
      abietaniphila BKME-9 and Zoogloea resiniphila DhA-35, were tested in laboratory
      sequencing batch reactors (SBRs) for their ability to enhance resin acid removal
      by biomass from a full-scale biotreatment system treating PPMEs. Both bacteria
      enhanced resin acid removal but not removal of total organic carbon (TOC) by
      either pH-shocked or starved activated sludge. These two bacteria also increased
      resin acid removal when the sludge was given high concentration (200 microM) of
      resin acid. A most-probable-number polymerase chain reaction (MPN-PCR) assay
      showed that these two bacteria were initially not detectable (detection limit:
      10(2) bacterial cells/ml) in the sludge community and were persistent after
      inoculation. Both bacteria did not substantially change the indigenous microbial
      community composition, as assayed by ribosomal intergenic spacer analysis (RISA).
      Our results suggest that it is feasible and potentially useful to enhance resin
      acid removal by bioaugmentation using resin-acid-degrading bacteria such as BKME
      9 and DhA-35.

PMID- 11235884
TI  - Water quality factors affecting bromate reduction in biologically active carbon
      filters.
AB  - Biological removal of the ozonation by-product, bromate, was demonstrated in
      biologically active carbon (BAC) filters. For example, with a 20-min EBCT, pH
      7.5, and influent dissolved oxygen (DO) and nitrate concentrations 2.1 and 5.1
      mg/l, respectively, 40% bromate removal was obtained with a 20 microg/l influent
      bromate concentration. In this study, DO, nitrate and sulfate concentrations, pH,
      and type of source water were evaluated for their effect on bromate removal in a
      BAC filter. Bromate removal decreased as the influent concentrations of DO and
      nitrate increased, but bromate removal was observed in the presence of measurable
      effluent concentrations of DO and nitrate. In contrast, bromate removal was not
      sensitive to the influent sulfate concentration, with only a slight reduction in
      bromate removal as the influent sulfate concentration was increased from 11.1 to
      102.7 mg/l. Bromate reduction was better at lower pH values (6.8 and 7.2) than at
      higher pH values (7.5 and 8.2), suggesting that it may be possible to reduce
      bromate formation during ozonation and increase biological bromate reduction
      through pH control. Biological bromate removal in Lake Michigan water was very
      poor as compared to that in tapwater from a groundwater source. Bromate removal
      improved when sufficient organic electron donor was added to remove the nitrate
      and DO present in the Lake Michigan water, indicating that the poor
      biodegradability of the natural organic matter may have been limiting bromate
      removal in that water. Biological bromate removal was demonstrated to be a
      sustainable process under a variety of water quality conditions, and bromate
      removal can be improved by controlling key water quality parameters.

PMID- 11235885
TI  - Potamon: a dynamic model for predicting phytoplankton composition and biomass in
      lowland rivers.
AB  - POTAMON is a unidimensional, non-stationary model, designed for simulating
      potamoplankton from source to mouth. The forcing variables are discharge, river
      morphology, water temperature, available light and nutrient inputs. Given the
      description of several algal categories, POTAMON allows to simulate algal
      "successions" at a particular site, as well as longitudinal changes of
      potamoplankton composition and biomass. The algal categories differ by their
      physiology, their loss rates, and their sensitivity to grazing by zooplankton.
      Two zooplankton categories were considered, Brachionus-like and Keratella-like,
      which differ by their clearance rate, their incipient limiting level, their
      selectivity towards phytoplankton, and their growth yield. The model simulates
      satisfactorily the onset and the magnitude of the phytoplankton spring bloom in
      the Belgian part of R. Meuse, the biomass decrease in early summer, and the
      autumn bloom. It also renders the major variations of algal assemblages along the
      river. The model allows to confirm that the main driving variables of
      potamoplankton dynamics in a eutrophic river are physical factors: discharge and
      related variables (e.g. retention time), light and temperature. In addition, the
      simulations confirm that the zooplankton-phytoplankton interaction may result in
      phytoplankton biomass fluctuations and compositional changes. POTAMON can be
      useful to explore plankton dynamics in a large river, and it may become a tool to
      test various management measures.

PMID- 11235886
TI  - The role of indigenous microorganisms in suppression of Salmonella regrowth in
      composted biosolids.
AB  - Composting is commonly used as an effective means of stabilizing wastewater
      biosolids and reducing pathogens to very low concentrations. However, it has been
      shown that under certain conditions Salmonella can regrow in previously composted
      biosolids. Growth of seeded Salmonella typhimurium in composted biosolids ranging
      from two weeks to two years maturity was monitored. Results from sterile and non
      sterile composted biosolids were compared. Seeded S. typhimurium colonized
      rapidly in sterilized biosolids reaching a maximum population density of more
      than 10(8) g(-1). Growth of seeded S. typhimurium was suppressed in non
      sterilized compost with a maximum population density of less than 10(3) g(-1).
      There was a significant decline in the growth rate of seeded Salmonella in
      sterilized compost when the compost was stored, suggesting that bio-available
      nutrients declined with storage. However, in non-sterilized compost this was not
      the case. This suggests that the indigenous microflora play a significant role in
      suppression of Salmonella regrowth in composted biosolids. There was a strong
      negative correlation (-0.85) between the Salmonella inactivation rate and the
      maturity of compost in non-sterilized compost. The Salmonella inactivation rate
      was seven times higher in biosolids composting for two weeks as compared to
      compost stored for two years. This suggests that the antagonistic effect of
      indigenous microorganisms towards Salmonella declined with compost storage. It
      was concluded that all composted biosolids had a Salmonella regrowth potential.
      However, the indigenous microflora significantly reduced this regrowth potential.
      Long-term storage of compost is not recommended as this may increase the pathogen
      regrowth potential.

PMID- 11235888
TI  - pH sequential ozonation of domestic and wine-distillery wastewaters.
AB  - Domestic and wine-distillery wastewaters were treated by semi-batch and
      continuous pH sequential ozonations. The process involves a succession of acidic
      and alkaline wastewater pH conditions. The alkaline periods allow oxidation of
      organic matter by hydroxyl radical and produce carbonates that eventually would
      inhibit the oxidation. On the other hand, the acidic periods favour the
      development of direct ozone reactions and strip off carbonates as carbon dioxide
      from the wastewater. Experimental results of pH sequential ozonation showed
      degradation and removal rates of wastewater pollutants higher than those achieved
      at constant either acidic or basic pH. The most significant improvement of ozone
      efficiency and pollutants removal were obtained by controlling the number of
      cycles, pH and time of acidic and alkaline phases. Also, ozonated wastewaters
      showed high biodegradability as deduced from their BOD/COD ratios. The
      feasibility of treating domestic and wine-distillery wastewater by an integrated
      activated sludge (ASP)-pH sequential ozonation system was evaluated. Integrated
      ASP-ozonation at constant pH processes were also carried out for comparative
      purposes. In these combined experiments, pH sequential ozonation showed
      advantages compared to ozonation at constant pH in reducing global parameters
      such as COD, TOC and TKN, but ozonation at constant pH led to higher removal of
      polyphenols and UV254 absorbing compounds.

PMID- 11235887
TI  - MFO induction in fish by filtrates from chlorine dioxide bleaching of wood pulp.
AB  - Spent bleaching liquors from pulp bleached with chlorine dioxide were assessed
      for their potency to induce hepatic mixed function oxygenase enzymes (MFO) in
      rainbow trout, as indicated by activity of ethoxyresorufin-o-deethyase (EROD).
      Filtrates were collected from two kraft mills in Central Canada to assess the
      potency of filtrates from hardwood and softwood bleaching. All mill-scale
      bleaching filtrates induced MFO activity, and filtrates from softwood pulp
      bleaching appeared more potent than filtrates from hardwood bleaching. Filtrates
      from the final bleaching stage were most potent, and filtrates from the first
      stage were the least potent. In laboratory bench-scale bleaching experiments,
      pulp from softwood and hardwood kraft mills in Eastern Canada was bleached via an
      industry-standard 5-stage chlorine dioxide bleaching sequence. The filtrates were
      collected and used in fish bioassays to assess EROD-inducing potency. Potency of
      bench-scale filtrates varied depending on wood furnish (i.e. softwood vs.
      hardwood) and the bleaching stage, with all bench-scale filtrates being much
      weaker EROD inducers than mill-scale filtrates. Recycled paper mill washwater is
      a possible source of compounds causing increased potency of the mill-scale
      filtrates.

PMID- 11235889
TI  - Microscopic and macroscopic approaches of Cu(II) removal by FSM-16.
AB  - The removal of Cu(II) by a mesoporous material, FSM-16, was studied using
      electron paramagnetic resonance (EPR) spectroscopy and surface complexation
      modeling (SCM). Free copper ions, adsorbed and precipitated Cu(II) species were
      qualitatively identified by in situ EPR spectroscopy of Cu-FSM-16 suspensions at
      room temperature and at 77 K. In addition, the adsorbed species was identified as
      a Cu(II) species with an axial symmetry from an analysis of the EPR spectra of
      "dry" Cu-FSM-16 at 77 K. On the basis of the EPR results, the removal of Cu(II)
      as a function of pH under various experimental conditions was successfully
      simulated by assuming two removal mechanisms such as surface complexation and
      surface precipitation. In the acidic pH range (< pH 6), free copper ions were
      predominant, and surface complexed then surface precipitated species became
      dominant as the pH increased.

PMID- 11235890
TI  - Release of trace elements in wetlands: role of seasonal variability.
AB  - Dissolved concentrations were determined for Fe, Mn, Al, Cu, Zn, La, U, Th, Cd
      and As in a wetland and its recipient stream to reveal the effect of seasonal
      changes in environmental conditions on the cycling and transfer of trace elements
      at the transition between terrestrial and aquatic ecosystems. These preliminary
      results from the wetland show marked seasonal changes in dissolved concentration
      for all elements except Zn and Cu. Concentrations are found to be low until about
      mid-February and then increase abruptly. The onset of trace element release
      appears to coincide with a marked decline in redox potential and increase of
      organic carbon content. Because this decline is itself correlated with a
      pronounced increase in temperature and dissolved Fe. Mn and organic carbon
      content, we suggest that the microorganisms which use soil iron and manganese oxy
      hydroxides as electron acceptors catalyzed the change in redox conditions and
      induced an increase of DOC. Temporal changes were also observed in the recipient
      stream which showed marked positive concentration peaks during stormflow events
      (except Zn). The seasonal processes occurring in the wetland appear to play a
      major role in determining the amount of trace elements which are transferred from
      the wetland to the river.

PMID- 11235891
TI  - Hydraulic and purification behaviors and their interactions during wastewater
      treatment in soil infiltration systems.
AB  - Four three-dimensional lysimeters were established in a pilot laboratory with the
      same medium sand and either an aggregate-laden (AL) or aggregate-free (AF)
      infiltration surface and a 60- or 90-cm soil vadose zone depth to ground water.
      During 48 weeks of operation, each lysimeter was dosed 4 times daily with septic
      tank effluent (STE) at 5 cm/d (AL) or 8.4 cm/d (AF). Weekly monitoring was done
      to characterize the STE, percolate flow and composition, and water content
      distributions within the lysimeters. Bromide tracer tests were completed at weeks
      0, 8, and 45 and during the latter two times, ice nucleating active (INA)
      bacteria and MS-2 and PRD-1 bacteriophages were used as bacterial and viral
      surrogates. After 48 weeks, soil cores were collected and analyzed for chemical
      and microbial properties. The observations made during this study revealed a
      dynamic, interactive behavior for hydraulic and purification processes that were
      similar for all four lysimeters. Media utilization and bromide retention times
      increased during the first two months of operation with the median bromide
      breakthrough exceeding one day at start-up and increasing to two days or more.
      Purification processes were gradually established over four months or longer,
      after which there were high removal efficiencies (>90%) for organic constituents,
      microorganisms, and virus, but only limited removal of nutrients. Soil core
      analyses revealed high biogeochemical activity within the infiltrative zone from
      0 to 15 cm depth. All four lysimeters exhibited comparable behavior and there
      were no significant differences in performance attributable to infiltrative
      surface character or soil depth. It is speculated that the comparable performance
      is due to a similar and sufficient degree of soil clogging genesis coupled with
      bioprocesses that effectively purified the wastewater effluent given the adequate
      retention times and high volumetric utilization's of the sand media.

PMID- 11235892
TI  - Experimental design methodology applied to adsorption of metallic ions onto fly
      ash.
AB  - The objective of this study was to define operating conditions which would
      conciliate a high removal of the five metallic cations (Cu2+, Ni2+, Zn2+, Cd2+,
      Pb2+) and a low desorption of these metal ions from the contaminated sorbents. To
      achieve this goal the strategy relied on the use of experimental design
      methodology. The influence of four parameters (fly ash/lime mass ratio, type of
      fly ash/lime sorbent, solution temperature, and sorbent concentration) on the
      removal at pH = 5 and the stabilization of the five metallic ions was studied. In
      the first step, the influence of three parameters on the removal of Cu2+ ions was
      studied (R2 = fly ash/lime mass ratio, type of sorbent, temperature). It was
      found that the same set of parameter values would produce both the highest
      removal and the lowest desorption for this cation: R2 = 9 g g(-1), sorbent B
      (made by mixing fly ash and lime in water, then drying this paste at 105 degrees
      C for 24 h), temperature of suspension equal to 60 degrees C. The formation of
      calcium silicate hydrate (CSH), resulting from the pozzolanic activity of fly
      ash, is assumed to be partially responsible for these mechanisms. In the second
      step, simplex methodology and Doehlert matrix were used to find the conditions in
      a 2D space (sorbent concentration, temperature of solution) that would give the
      highest removal from a solution containing five metallic cations and the lowest
      desorption of these five cations adsorbed on the contaminated sorbents. Then, the
      system response that had to be optimized was the total metallic ions
      concentration (TMIC, mol L(-1)). A TMIC was measured both for adsorption and
      leaching experiments. These responses were modelized using a second-order
      polynomial and the surface responses were plotted for adsorption and desorption
      results. A difference was observed between operating conditions reaching the
      highest adsorption from those that gave the lowest desorption. However, an
      adsorbent concentration around 122 g L(-1) and a solution temperature of 66
      degrees C would lead simultaneously to a high adsorption and a low desorption.

PMID- 11235893
TI  - Comparison of mineral and soluble iron Fenton's catalysts for the treatment of
      trichloroethylene.
AB  - Contaminant degradation, stoichiometry, and role of hydroxyl radicals (OH*) in
      four Fenton's systems were investigated using trichloroethylene (TCE) as a model
      contaminant. A standard Fenton's system, a modified soluble iron system with a
      pulse input of hydrogen peroxide, and two modified mineral-catalyzed systems (pH
      3 and 7) were studied. In the standard Fenton's system, which had the most
      efficient reaction stoichiometry, 78% of the TCE was degraded; however, chloride
      analysis indicated that no more than two of the three chlorines were displaced
      per TCE molecule degraded. Although the modified soluble iron system was
      characterized by 91% TCE degradation, chloride analysis also indicated that no
      more than two of the chlorines were lost from the TCE. In the goethite system of
      pH 3, > 99% of the TCE was degraded. Near-complete release of chloride suggested
      that the TCE may have been mineralized. Only 22% degradation of TCE was achieved
      in the pH 7 goethite system. and there was minimal release of chloride. The
      mineral-catalyzed reactions exhibited the least efficient reaction stoichiometry
      of the four systems. Experiments using hydroxyl radical scavengers showed that
      the standard Fenton's system degraded TCE entirely by hydroxyl radical
      mechanisms, while approximately 10-15% of the degradation achieved in the
      modified soluble iron and goethite-catalyzed systems at pH 3 was mediated by non
      hydroxyl radical mechanisms. In the goethite system at pH 7, only non-hydroxyl
      radical mechanisms were found. The goethite-catalyzed system at pH 3 effectively
      degraded the parent compound and may have the potential to mineralize
      contaminants when used for in situ soil and groundwater remediation and ex situ
      waste stream treatment in packed-bed reactors.

PMID- 11235894
TI  - Characterization of isolated fractions of dissolved organic matter from natural
      waters and a wastewater effluent.
AB  - Dissolved organic matter (DOM) was concentrated from natural waters and the
      effluent of a wastewater treatment plant using a portable reverse osmosis (RO)
      system. The humic acid (HA), fulvic acid (FA) and hydrophilic (HyI) fractions
      were isolated and purified by the XAD-8 resin combined with the cation exchange
      resin method. The FA fractions predominated in natural waters and accounted for
      54-68% of the total amount of dissolved organic carbon (DOC), whereas the HA and
      HyI fractions constituted, respectively, 13-29 and 9-30% of the total DOC. The
      effluent of wastewater was almost devoid of HA and the HyI fraction exceeded FA.
      The elemental compositions of HA and FA were in the ranges typical for natural
      humic materials, but the HyI fractions did not exhibit humic character. 1H NMR
      spectra revealed that the HyI fractions were almost devoid of aromatic protons
      and the aliphatic region featured more sharp signals than HA and FA fractions,
      indicating that HyI fractions were consisted of more simple compounds and less
      complex mixtures. The aliphatic functional groups in these fractions of DOM
      samples followed the order HA < FA <HyI. Proton titrations indicated that HA. FA
      and HyI fractions of DOM samples from different sources had similar total acidity
      whose range was 9.0-11.6 meq/g C. This similarity may be due to the sample
      fractionation method. The copper titration results showed that the number of
      total Cu binding sites for the three fractions of different DOM samples were
      quite similar (1.46-1.60 mmol/g C), which was consistent with the similarity in
      total acidity from proton titrations. The affinity of copper with each isolated
      fraction followed the order HA approximately = FA > HyI. The rate of Cu
      complexation with the HyI fraction was faster than the rate with the HA or FA
      fraction of the Suwannee River DOM, implying that copper reacted with relatively
      weak ligands faster than with strong ligands.

PMID- 11235895
TI  - Nonpoint source pollution: a distributed water quality modeling approach.
AB  - A distributed water quality model for nonpoint source pollution modeling in
      agricultural watersheds is described in this paper. A water quality component was
      developed for WATFLOOD (a flood forecast hydrological model) to deal with
      sediment and nutrient transport. The model uses a distributed group response unit
      approach for water quantity and quality modeling. Runoff, sediment yield and
      soluble nutrient concentrations are calculated separately for each land cover
      class, weighted by area and then routed downstream. With data extracted using
      Geographical Information Systems (GIS) technology for a local watershed, the
      model is calibrated for the hydrologic response and validated for the water
      quality component. The transferability of model parameters to other watersheds,
      especially those in remote areas without enough data for calibration, is a major
      problem in diffuse modeling. With the connection to GIS and the group response
      unit approach used in this paper, model portability increases substantially,
      which will improve nonpoint source modeling at the watershed-scale level.

PMID- 11235896
TI  - P2Y-purinoceptor mediated inhibition of L-type Ca2+ channels in rat pancreatic
      beta-cells.
AB  - We used the patch-clamp technique to study the effects of extracellular ATP on
      the activity of ion channels recorded in rat pancreatic beta-cells. In cell
      attached membrane patches, action currents induced by 8.3 mM glucose were
      inhibited by 0.1 mM ATP, 0.1 mM ADP or 15 microM ADPbetaS but not by 0.1 mM AMP
      or 0.1 mM adenosine. In perforated membrane patches, action potentials were
      measured in current clamp, induced by 8.3 mM glucose, and were also inhibited by
      0.1 mM ATP with a modest hyperpolarization to -43 mV. In whole-cell clamp
      experiments, ATP dose-dependently decreased the amplitudes of L-type Ca2+ channel
      currents (ICa) to 56.7+/-4.0% (p<0.001) of the control, but did not influence ATP
      sensitive K+ channel currents observed in the presence of 0.1 mM ATP and 0.1 mM
      ADP in the pipette. Agonists of P2Y purinoceptors, 2-methylthio ATP (0.1 mM) or
      ADPbetaS (15 microM) mimicked the inhibitory effect of ATP on ICa, but PPADS (0.1
      mM) and suramin (0.2 mM), antagonists of P2 purinoceptors, counteracted this
      effect. When we used 0.1 mM GTPgammaS in the pipette solution, ATP irreversibly
      reduced ICa to 58.4+/-6.6% of the control (p<0.001). In contrast, no inhibitory
      effect of ATP was observed when 0.2 mM GDPbetaS was used in the pipette solution.
      The use of either 20 mM BAPTA instead of 10 mM EGTA, or 0.1 mM compound 48/80, a
      blocker of phospholipase C (PLC), in the pipette solution abolished the
      inhibitory effect of ATP on ICa, but 1 microM staurosporine, a blocker of protein
      kinase C (PKC), did not. When the beta-cells were pretreated with 0.4 microM
      thapsigargin, an inhibitor of the endoplasmic reticulum (ER) Ca2+ pump, ATP lost
      the inhibitory effect on ICa. These results suggest that extracellular ATP
      inhibits action potentials by Ca2+-induced ICa inhibition in which an increase in
      cytosolic Ca2+ released from thapsigargin-sensitive store sites was brought about
      by a P2Y purinoceptor-coupled G-protein, PI-PLC and IP3 pathway.

PMID- 11235897
TI  - Novel actin cytoskeleton: actin tubules.
AB  - In spores of Dictyostelium discoideum three actin filaments are bundled to form a
      novel tubular structure and the tubules are then organized into rods. These
      tubular structures we will term actin tubules. Actin tubules are reconstructed
      from the supernatant of spore homogenates, while the usual actin filaments were
      bundled after incubation of supernatants from growing cells. Alpha-actinin, ABP
      120 and EF-1alpha are not essential for rod formation. Cofilin is a component of
      the cytoplasmic rods but few cofilin molecules are included in the nuclear rods.
      The viability of spores lacking actin rods is very low, and the spore shape is
      round instead of capsular. The rods can be fragmented by pressure, indicating
      that the rods may be effective in absorbing physical pressure. The complex
      organization of actin filaments, actin tubules and rods may be required for
      spores to achieve complete dormancy and maintain viability.

PMID- 11235898
TI  - Establishment and characterization of a colonic epithelial cell line MCE301 from
      transgenic mice harboring temperature-sensitive simian virus 40 large T-antigen
      gene.
AB  - We produced an immortalized colonic epithelial cell line, MCE301, using fetal
      mice transgenic for the temperature-sensitive simian virus 40 large T-antigen
      gene. MCE301 cells showed epithelial-like morphology and maintained tight
      connections with neighboring cells. The cells grew at a permissive temperature
      (33 degrees C), but the growth of the cells was significantly prevented at the
      nonpermissive temperature (39 degrees C). The cells expressed large T-antigen at
      33 degrees C but not at 39 degrees C. MCE301 cells were not transformed, as
      judged by the absence of anchorage-independent growth in soft agar gel and lack
      of tumor formation in nude mice. Electron microscopic studies showed that the
      cells formed microvilli-like structures on the cell surface and junctional
      complexes such as tight junctions and desmosomes between the cells. The cells
      expressed cytosketal (acidic cytokeratins and actin), basement membrane (laminin
      and collagen type IV) and junctional complex proteins (ZO-1 and desmoplakin I +
      II), as judged by specific antibodies. Fetal bovine serum, epidermal growth
      factor, insulin-like growth factor and insulin significantly increased the cell
      growth at 33 degrees C. Moreover, MCE301 cells expressed colonic mucin Muc2 mRNA
      as demonstrated by reverse transcriptase-polymerase chain reaction, indicating
      that the cells originate from mucus-secreting cells. Alkaline phosphatase, a
      brush border-associated enzyme, was detected in the cells. Sodium butyrate (2
      mM), an inducer of cellular differentiation, markedly elevated alkaline
      phosphatase activity. Thus, the present mouse colonic epithelial cell line MCE301
      possessing these unique characteristics should provide a useful in vitro model of
      colonic epithelium.

PMID- 11235899
TI  - Insulin-degrading enzyme exists inside of rat liver peroxisomes and degrades
      oxidized proteins.
AB  - Insulin-degrading enzyme (IDE) was detected by immunoblot analysis in highly
      purified rat liver peroxisomes. IDE in the peroxisomal fraction was resistant to
      proteolysis by trypsin and chymotrypsin under conditions where the peroxisomal
      membranes remained intact. After sonication of the peroxisomal fraction, IDE was
      recovered in the supernatant fraction. Further, the localization of IDE in the
      peroxisomes was shown by immunoelectron microscopy. In addition, IDE isolated
      from peroxisomes degraded insulin as well as oxidized lysozyme as a model
      substrate for oxidized proteins. These results suggest that IDE exists in an
      active form in the matrix of rat liver peroxisomes and is involved in elimination
      of oxidized proteins in peroxisomes.

PMID- 11235900
TI  - Domain analysis of the tetraspanins: studies of CD9/CD63 chimeric molecules on
      subcellular localization and upregulation activity for diphtheria toxin binding.
AB  - CD9 and CD63 belong to a tetramembrane-spanning glycoprotein family called
      tetraspanin, and are involved in a wide variety of cellular processes, but the
      structure-function relationship of this family of proteins has yet to be
      clarified. CD9 associates with diphtheria toxin receptor (DTR), which is
      identical to the membrane-anchored form of heparin-binding EGF-like growth factor
      (proHB-EGF). CD9 upregulates the diphtheria toxin (DT) binding activity of
      DTR/proHB-EGF, while CD63 does not upregulate the DT binding activity in spite of
      the fact that this protein also associates with DTR/proHB-EGF on the cell
      surface. CD9 molecules localize on the cell surface, while those of CD63 localize
      predominantly at lysosomes and intracellular compartments. We made CD9/CD63
      chimeric molecules and then studied their intracellular localization and
      upregulation activities. The C-terminal regions of CD63, which includes the
      lysosome sorting motif, showed a strong inhibitory effect on the expression of
      the chimeric proteins at the cell surface, while mutants lacking the lysosome
      sorting motif delivered more efficiently on the cell surface, indicating that the
      lysosome sorting motif contributes to the inhibitory effect of the C-terminal
      region. However, the N-terminal half of this family of proteins containing the
      1st to 3rd transmembrane domains also seems to influence the cell surface
      expression. For the upregulation of DT binding activity the large extracellular
      loop (EC2) of CD9 was essential, while the remaining regions influenced the
      upregulation activity by changing the efficiency of cell surface expression. From
      these results we discussed the structure-function relationship of this family of
      proteins.

PMID- 11235901
TI  - Peripheral T-cell lymphoma with aberrant expression of CD79a and CD20: a
      diagnostic pitfall.
AB  - Immunohistochemical studies are increasingly used for the routine diagnosis of
      lymphomas as it is widely accepted that lymphomas of different cell lineages vary
      in their prognosis and response to therapy. A case of peripheral T-cell lymphoma
      with aberrant expression of B-cell-associated antigens L-26 (CD20) and mb-1 (CD
      79a) is described. The disease pursued an aggressive clinical course, and the
      patient died of disease 6 weeks after presentation. Immunohistochemical studies
      demonstrated expression of both T- and B-cell-associated antigens, including CD3,
      CD8, CD43, TIA-1, CD20, and CD79a. Other markers expressed by the tumor cells
      included CD56 and S-100. Of interest, betaF-1 staining for the beta chain of T
      cell receptor (TCR) complex was positive in the small admixed T lymphocytes but
      was negative in the tumor cells, raising the possibility of a gamma/delta T-cell
      lymphoma. Molecular studies by polymerase chain reaction (PCR) demonstrated
      clonal TCR-gamma chain gene rearrangement without evidence for a clonal
      rearrangement of the immunoglobulin heavy chain gene. PCR for HHV-8 related
      sequences was negative. Mb-1 is an IgM-associated protein that was thought to be
      restricted to normal and neoplastic B cells. Although its coexpression has been
      reported in up to 10% cases of precursor T-cell lymphoblastic lymphoma, the
      coexpression of both CD20 and CD79a has not been described in mature T-cell
      malignancies. Biphenotypic lymphomas associated with HHV-8 have been reported in
      immunodeficiency, but no evidence of immune deficiency was identified, and
      studies for EBV and HHV-8 were negative. This case illustrates that no marker has
      absolute lineage specificity and that immunophenotypic studies should always be
      performed with panels of monoclonal antibodies. Moreover, cases with ambiguous
      phenotypes may require genotypic studies for precise lineage assignment.

PMID- 11235902
TI  - Langerhans cell histiocytosis involving the thyroid and parathyroid glands.
AB  - Langerhans cell histiocytosis (LCH) is a rare illness, and the disease afflicting
      the thyroid gland is very uncommon, even in the presence of multisystem
      involvement. In this report, we document histologically, for the first time,
      concurrent involvement of the thyroid and parathyroid glands by LCH. A young
      Chinese woman with a history of diabetes insipidus and hypogonadism underwent a
      total thyroidectomy for enlarged thyroid gland secondary to LCH causing airway
      obstruction. Microscopic examination of the excised specimen disclosed CD1a- and
      S-100-positive LCH cells involving the thyroid and parathyroid glands. In a
      patient with LCH affecting the thyroid gland, parathyroid gland disease should be
      suspected when the serum calcium levels are depressed in association with an
      inappropriate serum parathyroid hormone level, such as a normal parathyroid
      hormone level in this case.

PMID- 11235903
TI  - Preservation of RNA for functional genomic studies: a multidisciplinary tumor
      bank protocol.
AB  - Few human tumors are collected such that RNA is preserved for molecular analysis.
      Completion of the Human Genome Project will soon result in the identification of
      more than 100,000 new genes. Consequently, increasing attention is being diverted
      to identifying the function of these newly described genes. Here we describe a
      multidisciplinary tumor bank procurement protocol that preserves both the
      integrity of tissue for pathologic diagnosis, and the RNA for molecular analyses.
      Freshly excised normal skin was obtained from five patients undergoing wound
      reconstruction following Mohs micrographic surgery for cutaneous neoplasia.
      Tissues treated for 24 hours with RNAlater were compared histologically and
      immunohistochemically to tissues not treated with RNAlater. Immunohistochemical
      stains studied included: CD45, CEA, cytokeratin AE1/3, vimentin, S-100, and CD34
      on formalin-fixed, paraffin embedded tissue and CD45 staining of frozen tissue.
      Slides were blinded and evaluated independently by three pathologists. The
      histologic and immunohistochemical parameters of tissue stored in RNAlater were
      indistinguishable from tissue processed in standard fashion with the exception of
      S-100 stain which failed to identify melanocytes or Langerhan's cells within the
      epidermis in any of the RNAlater-treated tissues. Interestingly, nerve trunks
      within the dermis stained appropriately for S-100. Multiple non-cutaneous autopsy
      tissues were treated with RNAlater, formalin, liquid nitrogen (LN2), and TRIzol
      Reagent. The pathologists were unable to distinguish between tissues treated with
      RNAlater, formalin, or frozen in LN2, but could easily distinguish tissues
      treated with TRIzol Reagent because of extensive cytolysis. RNA was isolated from
      a portion of the tissue treated with RNAlater and used for molecular studies
      including Northern blotting and microarray analysis. RNA was adequate for
      Northern blot analysis and mRNA purified from RNAlater-treated tissues
      consistently provided excellent templates for reverse transcription and
      subsequent microarray analysis. We conclude that tissues treated with RNAlater
      before routine processing are indistinguishable histologically and
      immunohistochemically from tissues processed in routine fashion and that the RNA
      isolated from these tissues is of high quality and can be used for molecular
      studies. Based on this study, we developed a multidisciplinary tumor bank
      procurement protocol in which fresh tissue from resection specimens are routinely
      stored in RNAlater at the time of preliminary dissection. Thus, precious human
      tissue can be utilized for functional genomic studies without compromising the
      tissue's diagnostic and prognostic qualities.

PMID- 11235904
TI  - Megakaryopoiesis and myelofibrosis in chronic myeloid leukemia after allogeneic
      bone marrow transplantation: an immunohistochemical study of 127 patients.
AB  - An immunohistochemical and morphometric study was performed on 363 trephine
      biopsies of the bone marrow derived from 127 patients with chronic myeloid
      leukemia at standardized end points before and after allogeneic bone marrow
      transplantation (BMT). The purpose of this investigation was to evaluate features
      of CD61+ megakaryopoiesis related to successful engraftment. Further, we tried to
      elucidate possible associations of this lineage, including precursor cells, with
      the platelet count and reticulin fibrosis during the pretransplant and,
      specifically, post-transplant periods. A significant correlation was recognizable
      between the quantity of CD61+ megakaryocytes and the platelet values before BMT
      and also after completed hematopoietic recovery. In the very early post
      transplant period, which is associated with severe thrombocytopenia, patchy
      regeneration of disarranged hematopoiesis occurred, including dysplastic
      megakaryocytes. According to planimetric measurements after BMT, the atypical
      micromegakaryocytes characteristic for chronic myeloid leukemia disappeared, and
      the engrafted donor bone marrow revealed a prevalence of normal-size cells of
      this lineage. On the other hand, normalization of megakaryocyte size was absent
      in sequential examinations of the few patients with a leukemic relapse who had a
      predominance of atypical dwarf forms comparable with chronic myeloid leukemia.
      Before BMT occurred, reticulin fiber density was significantly correlated with
      the number of CD61+ megakaryocytes and its precursor cell population. In 34
      patients with myelofibrosis that occurred after myelo-ablative therapy and BMT,
      an initial regression was followed by an insidious recurrence of fibers
      concentrated in the areas of regenerating hematopoiesis. This postgraft
      reappearance of reticulin fibrosis was significantly associated with the quantity
      of megakaryocytes. Regarding engraftment parameters, pretransplant presence of
      (reticulin) myelofibrosis exerted a distinctive impact because of a delayed
      hematopoietic reconstitution according to standard clinical criteria. In line
      with this finding, slowed engraftment was also significantly related with higher
      pretransplant megakaryocyte and platelet counts.

PMID- 11235905
TI  - Deregulated expression of cell cycle-associated proteins in solid pseudopapillary
      tumor of the pancreas.
AB  - Solid pseudopapillary tumor of the pancreas was studied in a 20-year-old woman
      and a 54-year-old woman. In the younger patient, the tumor had metastasized to
      the liver 8 years after distal pancreatectomy. In both neoplasms, the distinct
      histologic pattern of solid, pseudopapillary, and degenerative cystic areas was
      present. Analysis by means of immunohistochemistry revealed a diffuse expression
      for vimentin, neuron-specific enolase, and a focal positivity for al-antitrypsin,
      whereas epithelial markers were negative in the tumor of the older patient and
      only focally expressed in the tumor of the younger patient. Immunohistochemical
      analysis of cell cycle-associated proteins provided an overexpression of cyclin
      D1 and cyclin D3 in both tumors, although to varying degrees. In addition, the
      cyclin-dependent kinase inhibitors p21, and to a lesser extent p27, were up
      regulated just as mdm2. There was no accumulation of p53 protein, and Ki67
      positive cells were extremely scarce. Analysis of the liver metastases showed an
      immunoreactive profile similar to that of the primary tumor. The results show a
      deregulation of the cell cycle with overexpression of cell cycle-activating
      proteins D1 and D3 and a probably counterbalancing upregulation of the cyclin
      dependent kinase inhibitors p21 and p27. The findings may explain the low pool of
      Ki67-reactive tumor cells and the generally good clinical outcome of these
      tumors. Whether a more profound dysbalance of the cell cycle regulation is
      responsible for the development of metastatic disease remains to be clarified.

PMID- 11235906
TI  - Analysis of intratumoral heterogeneity of chromosome 3p deletions and genetic
      evidence of polyclonal origin of cervical squamous carcinoma.
AB  - Investigation on intratumoral genetic heterogeneity provides an important insight
      into the roles of genetic alterations in human carcinogenesis and clues to clonal
      origin of tumors. Intratumoral heterogeneity of genetic changes of cervical
      cancer has not been described so far. In this study, we analyzed the intratumoral
      heterogeneity of chromosome 3p deletions and X-chromosome inactivation patterns
      in multiple microdissected samples from each individual cervical cancer,
      attempting to understand the roles of 3p deletions in development of cervical
      cancer and its clonal origin. Totally, 120 normal and lesional samples from 14
      cases of fresh cervicalcancers were analyzed. Frequency and patterns of allelic
      losses of 3p were assessed by polymerase chain reaction (PCR) amplification of 12
      microsatellite markers flanking the frequently deleted regions of 3p, followed by
      Genescan analysis in an ABI 377 DNA sequencer. Loss of heterozygosity was
      recorded as heterogeneous pattern (LOH present in parts of samples or LOH
      involving different alleles among different samples) and homogeneous pattern (LOH
      involving identical alleles in all samples from the tumor). Allelic loss
      affecting at least one marker was detected in 8 of 14 cases (57%). Allelic
      losses, both homogeneous and heterogeneous, were frequently detected at FHIT gene
      region (D3S1300, 40% and 60%; D3S4103, 27.3% and 54.6%), 3p21.3-21.2 (D3S1478,
      27.3% and 45.5%), and 3p24.2-22 (D3S1283, 30% and 50%). Seven of eight LOH
      positive tumors exhibited homogeneous allelic loss involving at least one of
      these three 3p loci. Allelic losses were present in the CIN lesions synchronous
      with invasive lesions positive for LOH. Our findings suggest essential roles of
      genes on these 3p loci, particularly the FHIT gene in participating in clonal
      selection and early development of cervical cancer. Most interestingly, with the
      combination of LOH analysis and X-chromosome inactivation analysis, we provided
      the first clear genetic evidence of polyclonal origin of cervical invasive cancer
      in two of eight cases. This finding strongly suggests the importance of field
      defect (possible human papilloma virus) in cervical carcinogenesis.

PMID- 11235907
TI  - In situ hybridization and reverse transcription-polymerase chain reaction for
      cyclin D1 mRNA in the diagnosis of mantle cell lymphoma in paraffin-embedded
      tissues.
AB  - Mantle cell lymphoma (MCL) is characterized by the chromosomal translocation
      t(11;14), which involves rearrangement of the bcl-1 proto-oncogene to the
      immunoglobulin heavy chain gene and results in overexpression of cyclin D1 mRNA.
      In this study, we evaluated the diagnostic relevance of three methods that may be
      helpful in the diagnosis of MCL: in situ hybridization (ISH) and a stringent
      reverse transcriptase-polymerase chain reaction (RT-PCR) protocol for cyclin D1
      mRNA, and immunohistochemistry for cyclin D1 protein. The study group included 37
      paraffin-embedded specimens (25 from lymph nodes and 12 from extranodal tissues)
      from 30 patients. MCL diagnosis was performed according to the Revised European
      American Classification of Lymphoid Neoplasms. Twenty-nine patients with non-MCL
      lymphoproliferative disorders comprised the control group. Biotin-labeled ISH was
      performed in 28 cases of MCL, 24 (86%) of which were found to be positive. As
      shown by ISH in extranodal tissues, cyclin D1 mRNA was present not only in
      neoplastic lymphoid cells, but in other cell types as well. For this reason, RT
      PCR results were considered reliable for MCL diagnosis only on informative
      material (from tissues that do not normally express cyclin D1); this method was
      evaluated as positive in 16 of 18 (89%) MCL cases. Cyclin D1 immunopositivity was
      present in 20 of 29 (69%) MCL cases. No members of the control group were found
      to express cyclin D1 mRNA by either ISH or RT-PCR under the stringent conditions
      used. In conclusion, stringent RT-PCR for cyclin D1 expression can be helpful in
      MCL diagnosis in paraffin-embedded material from lymph nodes. ISH is a sensitive
      method for cyclin D1 mRNA detection; its sensitivity is superior to that of
      cyclin D1 immunohistochemistry and similar to that of the stringent RT-PCR used.
      ISH is very specific as well, clearly more specific than RT-PCR, because it
      allows the correlation of molecular findings with morphology. This method can be
      applied on all types of paraffin-embedded tissues and provides an accurate tool
      for MCL diagnosis.

PMID- 11235908
TI  - Atypical adenomatous hyperplasia of the lung: a probable forerunner in the
      development of adenocarcinoma of the lung.
AB  - An increasingly large body of work suggests that atypical adenomatous hyperplasia
      (AAH) of the lung may be a forerunner of pulmonary adenocarcinoma. Recognizing
      this fact, the World Health Organization now acknowledges the existence of AAH
      while noting difficulties that may be encountered in distinguishing AAH from the
      nonmucinous variant of bronchioloalveolar carcinoma. Regrettably, a universally
      acceptable definition of morphologic criteria for the diagnosis of AAH has not
      been achieved. This review of the literature examines the epidemiology, gross
      appearance, light microscopic findings, morphometry, immunohistochemistry, and
      molecular features of AAH and suggests a set of histopathologic features that may
      help the practicing pathologist identify this intriguing lesion. These features
      include the following: irregularly bordered focal proliferations of atypical
      cells spreading along the preexisting alveolar framework; prominent cuboidal to
      low columnar alveolar epithelial cells with variable degree of atypia but less
      than that seen in adenocarcinoma; increased cell size and nuclear-cytoplasmic
      ratio with hyperchromasia and prominent nucleoli, generally intact intercellular
      attachment of atypical cells with occasional empty-looking spaces between them
      without high cellularity and without tufting or papillary structures; and slight
      thickening of the alveolar walls on which the AAH cells have spread, with some
      fibrosis but without scar formation or significant chronic inflammation of the
      surrounding lung tissue. Several lines of evidence indicate that AAH is a lesion
      closely associated with adenocarcinoma of the lung, suggesting AAH may be
      involved in the early stage of a complex multistep carcinogenesis of pulmonary
      adenocarcinoma.

PMID- 11235909
TI  - Fatal neonatal echovirus 6 infection: autopsy case report and review of the
      literature.
AB  - A full-term, healthy male neonate was delivered by caesarian section to a 26-year
      old primigravida woman who had a history of fever and upper respiratory tract
      infection. On the fourth day of life, the neonate developed a sepsis-like
      syndrome, acute respiratory and renal failure, and disseminated intravascular
      coagulopathy. He died 13 days after birth. Postmortem examination revealed
      jaundice, anasarca, massive hepatic necrosis, adrenal hemorrhagic necrosis, renal
      medullary hemorrhage, hemorrhagic noninflammatory pneumonia, and severe
      encephalomalacia. Echovirus type 6 was isolated from blood, liver, and lungs.
      Although uncommon, echovirus type 6 infection may produce a spectrum of
      pathologic findings similar to those seen with the more commonly virulent
      echovirus type 11.

PMID- 11235910
TI  - Epstein-Barr virus-negative Hodgkin's lymphoma after mycosis fungoides: molecular
      evidence for distinct clonal origin.
AB  - The association of mycosis fungoides (MF) and Hodgkin's lymphoma is a relatively
      frequent occurrence, but the potential clonal relationship of the two neoplasms
      is still controversial. We report a case of a patient with a history of MF in
      Clinical Stage 1A who developed retroperitoneal lymphadenopathy 9 years after the
      initial diagnosis of MF. A bone marrow biopsy obtained at this time showed
      nodular involvement by a mixed cellular infiltrate with large, atypical cells
      consistent with Hodgkin and Reed-Sternberg (RS) cells. These atypical cells were
      positive for CD30 and CD15 and did not express B- or T-cell markers. In addition,
      they lacked evidence of infection by Epstein-Barr virus, both by
      immunohistochemical staining for latent membrane protein 1 and by in situ
      hybridization for EBER1/2. The background population consisted mainly of small T
      cells without morphological or phenotypical signs of malignancy. Review of the
      skin biopsy obtained 9 years before showed the typical features of MF. Polymerase
      chain reaction analysis of the T-cell receptor T-gene confirmed the presence of a
      clonal T-cell rearrangement in the skin specimen. The bone marrow biopsy,
      however, showed a polyclonal pattern both for the T-cell receptor gamma-gene, as
      well as for immunoglobulin heavy chain genes. Isolation of RS cells stained for
      CD30 was performed by laser capture microdissection. Polymerase chain reaction
      analysis of several groups of RS cells showed a reproducible biallelic
      rearrangement of IgH genes, which was confirmed by cloning and sequencing of
      polymerase chain reaction products. To our knowledge, this is the first case in
      which a distinct clonal origin of MF and Hodgkin's lymphoma arising in the same
      patient is clearly demonstrated, based on molecular analysis of microdissected RS
      cells.

PMID- 11235911
TI  - Poorly differentiated follicular thyroid carcinoma with rhabdoid phenotype: a
      clinicopathologic, immunohistochemical and electron microscopic study of two
      cases.
AB  - Poorly differentiated thyroid carcinomas with follicular cell phenotype are not
      well defined. Different diagnostic criteria have been employed for these tumors,
      including solid growth, nodular, trabecular, and insular patterns. Cytologic
      features, such as a predominance of tall and columnar cells, have been considered
      to be diagnostic of poorly differentiated carcinoma. However, there is no
      agreement among surgical pathologists regarding morphologic criteria for poorly
      differentiated thyroid carcinoma. We report two unique thyroid neoplasms that we
      interpreted as poorly differentiated follicular carcinomas. Nodular, trabecular,
      and sheetlike patterns predominated in both tumors. They were composed of cells
      that were focally immunoreactive for thyroglobulin and had large vesicular nuclei
      with prominent nucleoli. A variable number of cells showed rhabdoid phenotype.
      The rhabdoid inclusions did not stain for thyroglobulin but contained whorls of
      intermediate filaments that were vimentin positive. There were foci of necrosis
      and numerous mitotic figures. Both patients were adults and died with multiple
      pulmonary metastases. The presence of rhabdoid cells in poorly differentiated
      follicular carcinomas broadens the spectrum of tumors with rhabdoid phenotype.
      More cases are needed to determine whether the rhabdoid phenotype is a marker for
      poorly differentiated follicular carcinoma as well as an independent adverse
      prognostic factor.

PMID- 11235912
TI  - Human retinal pigment epithelium secretes a phospholipase A2 and contains two
      novel intracellular phospholipases A2.
AB  - The sensitivity of different phospholipase A2 (PLA2)-active fractions eluted from
      cation-exchange chromatography to para-bromophenacylbromide (pBPB), Ca2+-EGTA,
      DTT, heat, and H2SO4 indicates that human cultured retinal pigment epithelial
      (hRPE) cells probably contain two different intracellular PLA2 enzymes. Control
      experiments using "back-and-forth" thin-layer chromatography confirmed that, in
      our assay conditions, the generation of free fatty acids originated solely from
      PLA2 activity. Together with immunoblot experiments where no cross-reactivity was
      observed between the hRPE cytosolic PLA2 enzymes and several antisera directed
      against secretory PLA2s (sPLA2s) and cytosolic PLA2 (cPLA2), these findings
      suggest that intracellular hRPE PLA2s are different from well-known sPLA2s,
      cPLA2, and Ca2+-independent PLA2s. We also report an additional hRPE-PLA2 enzyme
      that is secreted and that exhibits sensitivity to pBPB, Ca2+-EGTA, DTT, heat, and
      H2SO4, which is characteristic of sPLA2 enzymes. This approximately 22-kDa PLA2
      cross-reacted weakly with an antiserum directed against porcine pancreatic group
      I sPLA2 but strongly with an antiserum directed against N-terminal residues 1-14
      of human synovial group II sPLA2, suggesting that this extracellular enzyme is a
      member of the sPLA2 class of enzymes. We thus conclude that there are three
      distinct PLA2 enzymes in cultured hRPE cells, including two novel intracellular
      PLA2s and a 22-kDa secreted sPLA2 enzyme.

PMID- 11235913
TI  - Addition of a c-myc epitope tag within the VEGF protein does not affect in vitro
      biological activity.
AB  - The overexpression of vascular endothelial growth factor (VEGF) has been strongly
      implicated in diseases involving neovascularization. VEGF exists in as many as
      six different isoforms, each showing a unique pattern of tissue distribution and
      activity. To investigate the effect of individual VEGF isoform overexpression in
      neovascular disease models, we inserted c-myc epitope tags into the three VEGF
      isoforms expressed in retinal pigment epithelial cells, VEGF121, VEGF165, and
      VEGF189. We found that the 12-amino acid insertion between the receptor binding
      and heparin binding domains did not affect VEGF transcription, translation, or
      secretion. In addition, VEGF isoforms containing the c-myc epitope tag were able
      to stimulate endothelial cell proliferation as efficiently as non-tagged VEGF
      isoforms and they could be individually identified by Western blotting and
      immunocytochemistry using the c-myc epitope specific monoclonal antibody 9E10.

PMID- 11235914
TI  - Glutamate dehydrogenase from liver of euthermic and hibernating Richardson's
      ground squirrels: evidence for two distinct enzyme forms.
AB  - Glutamate dehydrogenase (GDH) was purified to homogeneity from the liver of
      euthermic (37 degrees C body temperature) and hibernating (torpid, 5 degrees C
      body temperature) Richardson's ground squirrels (Spermophilus richardsonii). SDS
      PAGE yielded a subunit molecular weight of 59.5+/-2 kDa for both enzymes, but
      reverse phase and size exclusion HPLC showed native molecular weights of 335+/-5
      kDa for euthermic and 320+/-5 kDa for hibernator GDH. Euthermic and hibernator
      GDH differed substantially in apparent Km values for glutamate, NH4+, and alpha
      ketoglutarate, as well as in Ka and IC50 values for nucleotide and ion activators
      and inhibitors. Kinetic properties of each enzyme were differentially affected by
      assay temperature (37 versus 5 degrees C). For example, the Km for alpha
      ketoglutarate of euthermic GDH was higher at 5 degrees C (3.66+/-0.34 mM) than at
      37 degrees C (0.10+/-0.01 mM), whereas hibernator GDH had a higher affinity for
      alpha-ketoglutarate at 5 degrees C (Km was 0.98+/-0.08 mM at 37 degrees C and
      0.43+/-0.02 mM at 5 degrees C). Temperature effects on Ka ADP values of the
      enzymes followed a similar pattern; GTP inhibition was strongest with the
      euthermic enzyme at 37 degrees C and weakest with hibernator GDH at 5 degrees C.
      Entry into hibernation leads to stable changes in the properties of ground
      squirrel liver GDH that allow the enzyme to function optimally at the prevailing
      body temperature.

PMID- 11235915
TI  - Human growth factor receptor bound 14 binds the activated insulin receptor and
      alters the insulin-stimulated tyrosine phosphorylation levels of multiple
      proteins.
AB  - To identify proteins interacting in the insulin-signaling pathway that might
      define new pathways or regulate existing ones, we have employed the yeast two
      hybrid system. In a two-hybrid screen of a human liver cDNA library, we
      identified the human growth factor receptor bound 14 (hGrb14) adaptor protein as
      a partner of the activated insulin receptor. Additional analysis of the insulin
      receptor--hGrb14 interaction in the yeast two-hybrid system revealed that the SH2
      domain of hGrb14 was not the sole region involved in binding the activated
      insulin receptor. The insulin-stimulated interaction between hGrb14 and the
      insulin receptor was also observed in different mammalian cultured cell lines.
      This association was detected at 1 min of insulin stimulation and was maximal at
      10 nM and greater concentrations of insulin. Chinese hamster ovary cells stably
      expressing the insulin receptor (CHO-IR) and hGrb14 were used to examine the
      effects of hGrb14 overexpression on insulin-stimulated tyrosine phosphorylation
      of proteins; in general, increasing levels of hGrb14 expression resulted in a
      reduction in tyrosine phosphorylation. This decrease was demonstrated for the
      specific proteins src homology-containing and collagen-related protein (Shc),
      insulin receptor substrate-1 (IRS-1), and Downstream of tyrosine Kinase (Dok).
      The broad effects of hGrb14 overexpression on insulin-stimulated tyrosine
      phosphorylation suggest that it acts early in the insulin-signaling pathway.

PMID- 11235916
TI  - Hydroxyl radical adduct of 5-aminosalicylic acid: a potential marker of ozone
      induced oxidative stress.
AB  - The use of 5-aminosalicylic acid in assessment of reactive oxygen species
      formation was investigated by in vitro Fenton and ozonation reactions, and by in
      vivo ozone-exposure experiments. Enzymatic hydroxylation was evaluated by a
      microsomal assay. Fischer 344 male rats (250 g) injected with 5-aminosalicylic
      acid (100 mg x kg(-1) i.p.; 30 min) were exposed to ozone (0, 1, 2 ppm; nose
      only, 2 h); bronchoalveolar lavage, lung homogenates, and plasma were recovered.
      Oxidation products of 5-aminosalicylic acid were as follows: salicylic acid, by
      deamination; 2,3-dihydroxybenzoic acid and 2,5-dihydroxybenzoic acid, from
      radical or enzymatic hydroxylation; 5-amino-2-hydroxy-N,N'-bis(3-carboxy-4
      hydroxyphenyl)-1,4-benzoquinonediimine, a condensation product of oxidized 5
      aminosalicylic acid; and 5-amino-2,3,4,6-tetrahydroxybenzoic acid, attributed to
      hydroxyl radical attack without deamination, identified by HPLC electrochemical
      (HPLC-EC) detector system analysis and by GC-MS analysis of trimethylsilyl
      derivatives. 5-Aminotetrahydroxybenzoic acid was not formed enzymatically. 5
      Aminotetrahydroxybenzoic acid, but not 5-aminosalicylic acid, was significantly
      elevated in bronchoalveolar lavage (+86%) and lung homogenates (+56%) in response
      to 2 ppm ozone (p < 0.05); no significant changes were detected in plasma. The
      data indicate that hydroxylation of 5-aminosalicylic acid is a potential specific
      probe for in vivo oxidative stress.

PMID- 11235917
TI  - Characterization of a novel heterodimeric cathepsin L-like protease and cDNA
      encoding the catalytic subunit of the protease in embryos of Artemia franciscana.
AB  - Embryos and larvae of the brine shrimp, Artemia franciscana, contain a novel
      cathepsin L-like cysteine protease (ACP) composed of 28.5- and 31.5-kDa subunits.
      Both subunits of the ACP are glycosylated, and seven isoforms of the protease
      were identified by isoelectric focusing with pI values ranging from 4.6 to 6.2.
      Several clones containing sequences coding for the 28.5-kDa subunit of the ACP
      were isolated from an Artemia embryo cDNA library in lambda ZAP II. One clone of
      1229 bp, with an open reading frame of 1014 bp, was sequenced and found to
      contain 50-65% amino acid sequence identity with several members of the cathepsin
      L subfamily of cysteine proteases. The mature protein predicted from this
      sequence consisted of 217 amino acids with a mass of 23.5 kDa prior to post
      translational modifications. The mature protein showed 68.6% amino acid sequence
      identity with human cathepsin L and 73.9% identity with cathepsin L-like
      proteases from Sarcophaga. peregrina and Drosophila melanogaster. The full-length
      cDNA clone analyzed in this study (pCP-3b) was renamed AFCATL1 (A. franciscana
      Cathepsin L1) and the sequence has been deposited in the Genbank database,
      accession number AF147207. Northern blot analyses identified a single transcript
      of about 1.4 kb in both embryos and young larvae of Artemia. Southern blot
      analyses of Artemia genomic DNA treated with various restriction endonucleases
      indicated a single gene for the ACP. The catalytic subunit of the ACP was tightly
      associated with a 31.5-kDa protein, which may localize the protease to
      nonlysosomal sites in embryos and larvae.

PMID- 11235918
TI  - Tumour promoter mediated altered expression and regulation of ornithine
      decarboxylase and S-adenosylmethionine decarboxylase in H-ras-transformed
      fibrosarcoma cell lines.
AB  - Alterations in cellular growth are important in the progression of malignant
      disease. Cell growth regulation by tumour promoters can be complex. The present
      study demonstrates a novel link between alterations in phorbol ester tumour
      promoter mediated regulation during malignant conversion and the expression of
      ornithine decarboxylase and S-adenosylmethionine decarboxylase, key rate-limiting
      and regulatory activities in the biosynthesis of polyamines. H-ras-transformed
      mouse 10 T 1/2 cell lines exhibiting increasing malignant potential were
      investigated for possible phorbol ester tumour promoter mediated changes in
      ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) gene
      expression. Selective induction of ODC and SAMDC gene expression was observed,
      since in contrast to nontransformed parental 10 T1/2 cells, ras-transformed cells
      capable of benign tumour formation (NR3 cells) and ras-transformed cells capable
      of metastasis formation (C2 cells) exhibited marked alterations in the levels of
      ODC and SAMDC gene expression. Increased ODC gene and SAMDC gene expression in
      response to phorbol-12-myristate-13-acetate (PMA) treatment was found to involve
      transcriptional events in both NR3 cells and in C2 cells. Post-transcriptional
      events also played a role in the regulation of ODC gene expression in NR3 cells
      and in C2 cells, and in the regulation of SAMDC gene expression in C2 cells but
      not in NR3 cells. In NR3 cells, alterations in ODC and in SAMDC gene expression
      was an event requiring de novo protein synthesis, whereas in highly malignant C2
      cells, protein synthesis inhibition following cycloheximide treatment in
      cooperation with PMA resulted in an augmentation of both ODC and SAMDC gene
      expression. Evidence is presented to suggest that the PMA-mediated alterations in
      ODC and in SAMDC gene expression in NR3 cells and in C2 cells involved protein
      kinase C - mediated events. The status of the cellular polyamine levels was also
      an important determinant of the PMA-mediated alterations that occurred in ODC and
      in SAMDC expression in these H-ras transformed cells. Collectively, these results
      suggest that PMA can modulate ODC and SAMDC expression in H-ras transformed cells
      and that the mechanisms involved in the PMA- mediated regulation of ODC and SAMDC
      gene expression changes as a function of H-ras mediated cellular transformation
      and malignant progression. This study further suggests a mechanism of PMA
      stimulation of transformed cells wherein early alterations in the regulatory
      control of ODC and SAMDC gene expression are important and critical.

PMID- 11235919
TI  - A tale of two charges: distinct roles for an acidic and a basic amino acid in the
      structure and function of cytochrome c.
AB  - Cytochrome c is a small electron transport protein found in the intermembrane
      space of mitochondria. As it interacts with a number of different physiological
      partners in a specific fashion, its structure varies little over eukaryotic
      evolutionary history. Two highly conserved residues found within its sequence are
      those at positions 13 and 90 (numbering is based on the standard horse cytochrome
      c); with single exceptions, residue 13 is either Lys or Arg, and residue 90 is
      either Glu or Asp. There have been conflicting views on the roles to be ascribed
      to these residues, particularly residue 13, so the functional properties of a
      number of site-directed mutants of Saccaromyces cerevisiae iso-1 cytochrome c
      have been examined. Results indicate that the two residues do not interact
      specifically with each other; however, residue 13 (Arg) is likely to be involved
      in interactions between cytochrome c and other electrostatically oriented
      physiological partners (intermolecular), whereas residue 90 (Asp) is involved in
      maintaining the intrinsic structure and stability of cytochrome c
      (intramolecular). This is supported by molecular dynamics simulations carried out
      for these mutants where removal of the negative charge at position 90 leads to
      significant shifts in the conformations of neighboring residues, particularly
      lysine 86. Both charged residues appear to exert their effects through
      electrostatics; however, biological activity is significantly more sensitive to
      substitutions of residue 13 than of residue 90.

PMID- 11235920
TI  - Localization of myosin Va is dependent on the cytoskeletal organization in the
      cell.
AB  - Myosin V plays an important role in membrane trafficking events. Its implication
      in the transport of pigment granules in melanocytes and synaptic vesicles in
      neurons is now well established. However, less is known about its function(s) in
      other cell types. Finding a common function is complicated by the diversity of
      myosin V expression in different tissues and organisms and by its association
      with different subcellular compartments. Here we show that myosin V is present in
      a variety of cells. Within the same cell type under different physiological
      conditions, we observed two main cellular locations for myosin V that were
      dependent on the dynamics of the plasma membrane: in cells with highly dynamic
      membranes, myosin V was specifically concentrated at the leading edge in membrane
      ruffles, whereas in cells with less dynamic membranes, myosin V was enriched
      around the microtubule-organizing center. The presence of myosin V in the leading
      ruffling edge of the cell was induced by growth factor stimulation and was
      dependent on the presence of a functional motor domain. Moreover, myosin V
      localization at the microtubule-organizing center was dependent on the integrity
      of the microtubules. In polarized epithelial cells (WIF-B), where the microtubule
      organizing region is close to the actin-rich apical surface, one single pool of
      myosin V, sensitive to the integrity of both microtubules and actin filaments,
      was observed.

PMID- 11235921
TI  - Molecular cloning, expression, and regulation of hippocampal amyloid precursor
      protein of senescence accelerated mouse (SAMP8).
AB  - Alzheimer's disease (AD) is associated with increased expression of amyloid
      precursor protein (APP) with a consequent deposition of amyloid beta peptide
      (Abeta) which forms characteristic senile plaques. We have noticed that the
      senescence accelerated mouse (SAMP8), a strain of mouse that exhibits age
      dependent defects such as loss of memory and retention at an early age of 8-12
      months, also produces increased amounts of APP and Abeta similar to those
      observed in Alzheimer's disease (AD). In order to investigate if this is due to
      mutations in APP similar to those observed in AD, and to develop molecular probes
      that regulate its expression, APP cDNA was cloned from the hippocampus of 8-month
      old SAMP8 mouse. The nucleotide sequence is 99.7% homologous with that of mouse
      and rat, 88.7% with monkey, and 89.2% with human homologues. At the amino acid
      level, the homology was 99.2% and 97.6% with rodent and primate sequences,
      respectively. A single amino acid substitution of Alanine instead of Valine at
      position 300 was unique to SAMP8 mouse APP. However, no mutations similar to
      those reported in human familial AD were observed. When the cDNA was expressed in
      HeLa cells, glycosylated mature APP could be detected by immunoblotting
      technique. The expression could be regulated in a time- and concentration
      dependent manner by using an antisense oligonucleotide specific to APP mRNA. Such
      regulation of APP expression may have a therapeutic application in vivo.

PMID- 11235922
TI  - Intramuscular ziprasidone, 2 mg versus 10 mg, in the short-term management of
      agitated psychotic patients.
AB  - BACKGROUND: There is a clear need for effective, well-tolerated intramuscular
      (i.m.) agents for the acute control of agitated psychotic patients. Currently
      used agents, including conventional antipsychotics and/or benzodiazepines, may be
      associated with distressing side effects such as extrapyramidal side effects and
      excessive sedation. OBJECTIVE: The objective of this study was to evaluate the
      efficacy and tolerability of the rapid-acting i.m. formulation of the novel
      antipsychotic ziprasidone in the treatment of inpatients with psychosis and acute
      agitation (DSM-IV diagnoses). METHOD: In a 24-hour, double-blind, fixed-dose
      clinical trial, patients were randomly assigned to receive up to 4 injections
      (every 2 hours p.r.n.) of 2 mg (N = 54) or 10 mg (N = 63) of ziprasidone i.m. The
      Behavioral Activity Rating Scale measured behavioral symptoms at baseline and the
      response to treatment up to 4 hours after the first i.m. injection. RESULTS:
      Ziprasidone i.m., 10 mg, rapidly reduced symptoms of acute agitation and was
      significantly more effective (p < .01) than the 2-mg dose up to 4 hours after the
      first injection. Patients were calmed but not excessively sedated, and over half
      were classed as responders 2 hours after the 10-mg dose. No acute dystonia or
      behavioral disinhibition was reported. One patient who received the 10-mg dose
      experienced the extrapyramidal side effect akathisia. CONCLUSION: Ziprasidone
      i.m., 10 mg, is rapidly effective and well tolerated in the short-term management
      of the agitated psychotic patient. Comparison with a study of identical design
      comparing 2-mg with 20-mg doses in patients with similar levels of
      psychopathology suggests that efficacy with 10 mg or 20 mg of ziprasidone i.m. is
      significant and dose related.

PMID- 11235923
TI  - Gabapentin in the treatment of cocaine dependence: a case series.
AB  - BACKGROUND: Although multiple medications have been studied for the treatment of
      cocaine dependence, no medication has been shown to have a robust effect on
      craving and use. This pilot project was designed to evaluate the safety and
      tolerability of gabapentin in subjects with cocaine dependence. METHOD: Thirty
      cocaine-dependent subjects (DSM-IV criteria) were enrolled in an 8-week, open
      label trial of 1,200 mg/day of gabapentin in divided doses. Urine drug screens,
      subjective measures of craving, and cocaine use interviews were conducted at each
      weekly visit. RESULTS: Baseline rating of amount and frequency of craving
      decreased significantly by week 8 (78% vs. 25% for amount, p = .000; 74% vs. 23%
      for frequency, p = .004). Positive urine drug screens for cocaine decreased from
      86% at baseline to 29% at weeks 4 and 8. There were no reports of significant
      side effects or adverse events. CONCLUSION: This pilot study indicates that
      gabapentin is safe and well tolerated and may be beneficial in the treatment of
      cocaine dependence. A placebo-controlled trial would be of interest.

PMID- 11235925
TI  - Antidepressant-associated mania and psychosis resulting in psychiatric
      admissions.
AB  - BACKGROUND: The safety and tolerability of the selective serotonin reuptake
      inhibitors and the newer atypical agents have led to a significant increase in
      antidepressant use. These changes raise concern as to the likelihood of a
      corresponding increase in adverse behavioral reactions attributable to these
      drugs. METHOD: All admissions to a university-based general hospital psychiatric
      unit during a 14-month period were reviewed. RESULTS: Forty-three (8.1%) of 533
      patients were found to have been admitted owing to antidepressant-associated
      mania or psychosis. CONCLUSION: Despite the positive changes in the side effect
      profile of antidepressant drugs, the rate of admissions due to antidepressant
      associated adverse behavioral effects remains significant.

PMID- 11235924
TI  - Reemergence of sexual dysfunction in patients with major depressive disorder:
      double-blind comparison of nefazodone and sertraline.
AB  - BACKGROUND: Several different classes of antidepressants have been associated
      with sexual adverse effects. This double-blind, randomized trial compared the
      effects of nefazodone and sertraline on reemergence of sexual dysfunction in
      depressed patients who had experienced sexual dysfunction as a result of
      sertraline treatment. Depressive symptoms were also monitored. METHOD: One
      hundred five patients with DSM-III-R major depressive episode who were
      experiencing sexual dysfunction attributable to sertraline (100 mg/day) were
      screened for entry. Eligible patients entered a 1-week washout period that was
      followed by a 7- to 10-day single-blind placebo phase. Patients without symptoms
      of sexual dysfunction at the end of the single-blind placebo phase were randomly
      assigned to receive double-blind treatment with either nefazodone (400 mg/day) or
      sertraline (100 mg/day) for 8 weeks. RESULTS: Nearly 3 times more sertraline
      treated patients (76%; 25/33) experienced reemergence of sexual dysfunction
      (ejaculatory and/or orgasmic difficulty) than did nefazodone-treated patients
      (26%; 10/39) (p < .001). In addition, patients treated with nefazodone were more
      satisfied with their sexual functioning than were patients treated with
      sertraline. Both treatment groups demonstrated a similar and sustained
      improvement in depressive symptoms. Both drugs were well tolerated, and the
      overall incidence of adverse reactions was similar for both treatment groups;
      however, 9 sertraline-treated patients (26%) discontinued because of adverse
      events compared with 5 nefazodone-treated patients (12%). Of the patients
      discontinuing therapy for adverse events, 5 of the sertraline-treated patients
      did so because of sexual dysfunction reported as an adverse event, whereas only 1
      of the nefazodone-treated patients discontinued therapy secondary to sexual
      dysfunction. CONCLUSION: In this sample of patients with major depression who had
      recovered from sexual dysfunction induced by treatment with sertraline,
      nefazodone treatment resulted in significantly less reemergence of sexual
      dysfunction than did renewed treatment with sertraline and provided continued
      antidepressant activity.

PMID- 11235926
TI  - The effects of olanzapine in reducing the emergence of psychosis among nursing
      home patients with Alzheimer's disease.
AB  - BACKGROUND: Elderly patients with Alzheimer's disease (AD) commonly exhibit
      psychotic symptoms, prompting clinicians to administer antipsychotics. This
      article compares the effects of olanzapine and placebo in the emergence of
      hallucinations or delusions in AD patients with symptoms of agitation/aggression
      but little or no psychotic symptomatology at baseline. METHOD: A multicenter,
      double-blind, placebo-controlled study was conducted in nursing home patients
      with AD according to DSM-IV criteria and symptoms of agitation/aggression and/or
      psychosis. Patients (N = 206) were randomly assigned to receive either placebo or
      fixed-dose olanzapine (5, 10, or 15 mg/day) for up to 6 weeks. This article
      analyzes data from a subgroup of patients (N = 165) with no or minimal delusions
      and/or hallucinations at baseline as measured by the Neuropsychiatric Inventory
      Nursing Home Version (NPI/NH). Three subsets of patients were identified on the
      basis of their symptoms at baseline: those with no clinically significant
      hallucinations, those with no clinically significant delusions, and those with no
      clinically significant delusions or hallucinations. RESULTS: Of the patients
      without hallucinations or delusions at baseline (N = 75), the placebo-treated
      patients showed significantly greater development of these symptoms compared with
      olanzapine-treated patients overall (NPI/NH hallucinations + delusions mean
      change score, +2.73 vs. +0.27, p = .006). Similarly, of the patients without
      baseline hallucinations (N = 153), the placebo-treated patients showed greater
      hallucinations score increases than did olanzapine-treated patients overall
      (+1.25 vs. +0.33, p = .026), whereas patients without baseline delusions (N = 87)
      showed no significant treatment effects. Olanzapine had a favorable safety
      profile in each patient subset. CONCLUSION: These results suggest that, overall,
      olanzapine effectively attenuated emergence of psychosis in a short-term trial of
      patients with Alzheimer's disease.

PMID- 11235927
TI  - Melatonin in medically ill patients with insomnia: a double-blind, placebo
      controlled study.
AB  - BACKGROUND: It has been suggested that melatonin improves sleep functioning, but
      this possibility has not been studied in medical populations. METHOD: 33
      medically ill persons with initial insomnia were randomly assigned to receive
      either melatonin (N = 18) or placebo (N = 15) in a flexible-dose regimen. Double
      blind assessments of aspects of sleep functioning were obtained daily across the
      next 8 to 16 days. RESULTS: The mean stable dose of melatonin was found to be 5.4
      mg. Relative to placebo, melatonin significantly hastened sleep onset, improved
      quality and depth of sleep, and increased sleep duration without producing
      drowsiness, early-morning "hangover" symptoms, or daytime adverse effects (p <
      .05). Melatonin also contributed to freshness in the morning and during the day
      and improved overall daytime functioning. Benefits were most apparent during the
      first week of treatment. CONCLUSION: Melatonin may be a useful hypnotic for
      medically ill patients with initial insomnia, particularly those for whom
      conventional hypnotic drug therapy may be problematic.

PMID- 11235928
TI  - The natural history of psychosis and depression in dementia with Lewy bodies and
      Alzheimer's disease: persistence and new cases over 1 year of follow-up.
AB  - BACKGROUND: Few data are available regarding the natural course of psychiatric
      symptoms in dementia with Lewy bodies and Alzheimer's disease. To acquire this
      information is essential to inform differential diagnosis and treatment
      decisions. METHOD: The current study provides prospective data regarding a
      representative case-register cohort of patients with operationalized clinical
      diagnoses of dementia with Lewy bodies (N = 82) or Alzheimer's disease (N = 132),
      with verified accuracy of clinical diagnosis against postmortem examination.
      Psychosis (Columbia University Scale for Psychopathology in Alzheimer's Disease)
      and depression (Cornell Scale for Depression in Dementia) were assessed at
      baseline and annual follow-up. RESULTS: Visual hallucinations were significantly
      more likely to be persistent in patients suffering from dementia with Lewy bodies
      (chi2 = 19.1, df = 1, p < .0001). Although a number of other psychiatric symptoms
      were also more frequent at baseline in dementia with Lewy body patients, they
      were not significantly more likely to persist. Delusions and auditory
      hallucinations did, however, persist in more than 40% of patients across both
      diagnostic groups. Patients suffering from dementia with Lewy bodies were
      significantly more likely to develop new auditory hallucinations over the year of
      follow-up (chi2 = 14.4, df= 1, p < .0001). CONCLUSION: These results confirm
      that, although a number of psychiatric symptoms are common in dementia with Lewy
      bodies, it is only visual hallucinations that are significantly more persistent,
      with important treatment implications.

PMID- 11235929
TI  - Risperidone versus pimozide in Tourette's disorder: a comparative double-blind
      parallel-group study.
AB  - BACKGROUND: The treatment of Tourette's disorder with classical neuroleptics is
      limited by their side effects. Risperidone is a new efficacious antipsychotic
      with a low propensity for extrapyramidal side effects. To establish risperidone's
      therapeutic potential in Tourette's disorder, we studied the safety and efficacy
      of risperidone in comparison with pimozide in patients with Tourette's disorder
      diagnosed according to DSM-III-R. METHOD: In a 12-week, multicenter, double
      blind, parallel-group study, 26 patients were treated with risperidone (mean
      daily dose = 3.8 mg), and 24 patients were treated with pimozide (mean daily dose
      = 2.9 mg). RESULTS: There was significant improvement of tics with respect to the
      Tourette's Symptom Severity Scale (TSSS) for both groups. Forty-one patients
      completed the study. At endpoint, 54% (14/26) of the risperidone patients and 38%
      (9/24) of the pimozide patients had only very mild or no symptoms on the global
      severity rating of the TSSS. Both treatment groups had improved significantly at
      endpoint in regard to Global Assessment of Functioning and Clinical Global
      Impressions scale outcomes. Symptoms of anxiety and depressive mood improved
      significantly from baseline in both groups. Obsessive-compulsive behavior
      improvement reached significance only in the risperidone group. Although the
      severity of extrapyramidal side effects was low in both groups, fewer patients in
      the risperidone group reported extrapyramidal side effects (N = 4) compared with
      the pimozide group (N = 8). Depression, fatigue, and somnolence were reported as
      the most prominent side effects in both treatment groups. CONCLUSION: Both drugs
      were efficacious and well tolerated in patients with Tourette's disorder.
      Risperidone may become the first-line drug in the treatment of Tourette's
      disorder owing to a more favorable efficacy and tolerability profile.

PMID- 11235930
TI  - Thiazide diuretics and lithium levels.

PMID- 11235931
TI  - Lithium therapy for corticosteroid-induced mood disorder.

PMID- 11235932
TI  - Chilaiditi syndrome--associated schizophrenia: 3 case reports.

PMID- 11235933
TI  - Pharmacologic treatment of patients hospitalized with the diagnosis of
      schizoaffective disorder.

PMID- 11235934
TI  - Does evidence from clinical trials in psychopharmacology apply in clinical
      practice?
AB  - The art of psychopharmacology derives from the science of psychopharmacology, but
      still requires wisdom, judgment, and experience to translate findings from
      clinical trials of a new drug into clinical practice.

PMID- 11235935
TI  - Inositol in the treatment of trichotillomania and compulsive skin picking.

PMID- 11235936
TI  - Hypothermia in 2 patients treated with atypical antipsychotic medication.

PMID- 11235937
TI  - A retrospective review of clinical characteristics and treatment response in body
      dysmorphic disorder versus obsessive-compulsive disorder.
AB  - BACKGROUND: Although body dysmorphic disorder (BDD) has many features in common
      with obsessive-compulsive disorder (OCD) and is frequently comorbid with OCD, few
      studies have directly compared the 2 disorders. Although BDD and OCD respond to
      similar medications and cognitive-behavioral therapy (CBT), their response to
      treatment has never been directly compared. METHOD: We studied 107 consecutive
      patients with DSM-III-R OCD (N = 96) or BDD (N = 11) treated openly for 6 weeks
      with intensive CBT, medication, and psychosocial rehabilitation, in a specialized
      partial hospitalization program for severely ill OCD patients. All patients were
      assessed, before and after treatment, with the Yale-Brown Obsessive Compulsive
      Scale (Y-BOCS), Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating
      Scale for Anxiety (HAM-A), and Global Assessment Scale (GAS). Retrospectively, we
      compared the clinical characteristics, symptom severity, and response to
      treatment of BDD patients with those of OCD patients. RESULTS: BDD patients and
      OCD patients had similar sex ratio, age, treatment duration, prevalence of
      comorbid major depression, and pretreatment Y-BOCS and GAS scores. BDD patients
      had significantly higher pretreatment HAM-D and HAM-A scores. The proportions of
      patients treated with serotonin reuptake inhibitors and antipsychotics did not
      differ between groups. Both groups improved with treatment, with significant (p <
      .001) changes in Y-BOCS, HAM-D, HAM-A, and GAS scores. Change in Y-BOCS did not
      differ between groups, but changes in HAM-D and HAM-A were significantly greater
      in BDD patients than in OCD patients. CONCLUSION: While BDD may be associated
      with greater severity of depressive and anxiety symptoms than OCD, this study
      suggests that BDD may respond to intensive, multimodal treatment.

PMID- 11235938
TI  - Schizophrenia, obesity, and obstructive sleep apnea.
AB  - BACKGROUND: This study evaluated the risk factors for obstructive sleep apnea in
      psychiatric patients. METHOD: The subjects were 364 patients referred to a sleep
      disorders consultation service from an inpatient psychiatric hospital. Seventy
      eight percent underwent polysomnographic testing. Rates of obstructive sleep
      apnea in different diagnostic groups (established by clinical DSM-III-R
      diagnosis) were retrospectively assessed. RESULTS: Logistic regression
      demonstrated significant independent effects of age (p = .046), gender (p =
      .002), body mass index (p < .001), and chronic neuroleptic use (p = .012) on the
      presence of obstructive sleep apnea (defined as more than 20 instances of apnea
      and/or hypopnea per hour of sleep). Patients with schizophrenia were
      significantly heavier and had higher rates of sleep apnea than did other
      psychiatric patients. CONCLUSION: Obesity, male gender, and chronic neuroleptic
      administration are risk factors for obstructive sleep apnea in psychiatric
      patients. Since patients with schizophrenia are often on long-term neuroleptic
      treatment, they may have high rates of obstructive sleep apnea, mediated via the
      weight gain produced by such medications. Overweight psychiatric patients and
      those on chronic neuroleptic treatment (e.g., patients with schizophrenia) should
      be evaluated for sleep apnea if signs and symptoms of this disorder are present.

PMID- 11235939
TI  - Enigma of raised intracranial pressure in patients with complex craniosynostosis:
      the role of abnormal intracranial venous drainage.
AB  - OBJECT: In this study the authors investigated whether patterns of intracranial
      venous drainage in children with complex craniosynostosis associated with raised
      intracranial pressure (ICP) were abnormal and, thus, could support the theory
      that venous hypertension is a major contributor to raised ICP that can lead to
      impaired visual function or even blindness in these patients. METHODS: The
      authors analyzed the anatomy of intracranial venous drainage as demonstrated in
      the results of 24 angiography studies obtained in 23 patients, all of whom had
      either a craniosynostosis-related syndrome (18 patients) or a nonsyndromic
      multisutural synostosis (five patients). Twenty-one patients had experienced
      raised ICP (in 19 patients diagnosis was based on invasive ICP monitoring and in
      two patients on clinical grounds alone) 1 to 6 weeks before undergoing
      angiography. Of the two remaining patients (both with Apert syndrome) whose ICP
      monitoring was normal immediately before angiography, each had undergone two
      previous cranial vault expansion procedures. On results of 18 angiography studies
      a 51 to 99% stenosis or no flow at all could be observed in the sigmoid-jugular
      sinus complex either bilaterally (11 patients) or unilaterally (seven patients).
      In 11 of these patients a florid collateral circulation through the stylomastoid
      emissary venous plexus was also seen. Two angiography studies were performed in
      one patient with Crouzon syndrome. A comparison of the two studies demonstrated a
      progression of the abnormal venous anatomy in that case. The authors found no
      obvious correlation between each patient's baseline ICP and the degree of
      abnormality of their venous anatomy, as judged on the basis of a venous-phase
      angiography severity score. CONCLUSIONS: Based on their findings, the authors
      assert that in children with complex forms of craniosynostosis in whom other
      factors, such as hydrocephalus, are absent, abnormalities of venous drainage that
      particularly affect the sigmoid-jugular sinus complex produce a state of venous
      hypertension that, in turn, is responsible for the majority of cases of raised
      ICP. The incidence of these changes is unknown, but an analysis of the ages of
      the children in this study indicated that the period of particular vulnerability
      to the effects of venous hypertension lasts until the affected child is
      approximately 6 years old. After that age the collateral venous drainage through
      the stylomastoid plexus will likely become sufficient to allow ICP to normalize.

PMID- 11235940
TI  - Use of intercostal nerves for neurotization of the musculocutaneous nerve in
      infants with birth-related brachial plexus palsy.
AB  - OBJECT: The use of intercostal nerves (ICNs) for the neurotization of the
      musculocutaneous nerve (MCN) in adult patients with traumatic brachial plexus
      palsy has been well described. However, its use for brachial plexus palsy in
      infants has rarely been reported. The authors surgically created 31 ICN-MCN
      communications for birth-related brachial plexus palsy and present the surgical
      results. METHODS: Thirty-one neurotizations of the MCN, performed using ICNs,
      were conducted in 30 patients with birth-related brachial plexus palsy. In most
      cases other procedures were combined to reconstruct all upper-extremity function.
      The mean patient age at surgery was 5.8 months and the mean follow-up period was
      5.2 years. Intercostal nerves were transected 1 cm distal to the mammary line and
      their stumps were transferred to the axilla, where they were coapted directly to
      the MCN. Two ICNs were used in 26 cases and three ICNs in five cases. The power
      of the biceps muscle of the arm was rated Grade M4 in 26 (84%) of 31 patients. In
      the 12 patients who underwent surgery when they were younger than 5 months of
      age, all exhibited a grade of M4 (100%) in their biceps muscle power. These
      results are better than those previously reported in adults. CONCLUSIONS:
      Neurotization of the MCN by surgically connecting ICNs is a safe, reliable, and
      effective procedure for reconstruction of the brachial plexus in patients
      suffering from birth-related palsy.

PMID- 11235941
TI  - Two computerized methods used to analyze intracranial pressure B waves:
      comparison with traditional visual interpretation.
AB  - OBJECT: Slow and rhythmic oscillations in intracranial pressure (ICP), also known
      as B waves, have been claimed to be one of the best preoperative predictive
      factors in idiopathic adult hydrocephalus syndrome (IAHS). Definitions of B waves
      vary widely, and previously reported results must be treated with caution. The
      aims of the present study were to develop a definition of B waves, to develop a
      method to estimate the B-wave content in an ICP recording by using computer
      algorithms, and to validate these procedures by comparison with the traditional
      visual interpretation. METHODS: In eight patients with IAHS, ICP was continuously
      monitored for approximately 20 hours. The ICP B-wave activity as a percentage of
      total monitoring time (B%) was estimated by using visual estimation according to
      the definition given by Lundberg, and also by using two computer algorithms
      (Methods I and II). In Method I each individual wave was classified as a B wave
      or not, whereas Method II was used to estimate the B-wave content by evaluating
      the B-wave power in 10-minute blocks of ICP recordings. CONCLUSIONS: The two
      computerized algorithms produced similar results. However, with the amplitude set
      to 1 mm Hg, Method I yielded the highest correlation with the visual analysis (r
      = 0.74). At least 5 hours of monitoring time was needed for an acceptable
      approximation of the B% in an overnight ICP recording. The advantages of using
      modern technology in the analysis of B-wave content of ICP are obvious and these
      methods should be used in future studies.

PMID- 11235942
TI  - Intracerebral microdialysis in neurointensive care: the use of urea as an
      endogenous reference compound.
AB  - OBJECT: When evaluating the results of intracerebral microdialysis, the in vivo
      performance of the microdialysis probe must be considered, because this
      determines the fraction of the interstitial concentration obtained in the
      microdialysis samples. The in vivo performance is dependent on several factors,
      for example, the interstitial compartment's diffusion characteristics, which may
      vary during the course of the acute brain injury process. In the present study
      the authors investigated the method of controlling the in vivo performance by
      using urea, which is evenly distributed in all body fluid compartments, as an
      endogenous reference compound and by comparing the urea levels in three
      compartments: the brain (CNS), abdominal subcutaneous tissue (SC), and blood
      serum (BS). METHODS: Sixty-nine patients with traumatic brain injury or
      cerebrovascular disease were included in the study. In 63 of these patients a CNS
      probe was used, an SC probe was used in 40, and both were used in 34. Urea was
      measured by enzymatic methods, at bedside for the microdialysis samples and in
      routine clinical laboratory studies for the BS samples, with the probe calibrated
      to give identical results. The correlation coefficient for CNS/SC urea was 0.88
      (2414 samples), for CNS/BS urea it was 0.89 (180 samples), and for SC/BS urea it
      was 0.98 (112 samples). CONCLUSIONS: Urea levels in the CNS, SC, and BS were
      highly correlated, which supports the assumption that urea is evenly distributed.
      The CNS/SC urea ratio can therefore be used for monitoring the CNS probe's in
      vivo performance. Fluctuations in other substances measured with microdialysis
      are probably caused by biological changes in the brain, as long as the CNS/SC
      urea ratio remains constant.

PMID- 11235943
TI  - Effects of hyperbaric oxygenation therapy on cerebral metabolism and intracranial
      pressure in severely brain injured patients.
AB  - OBJECT: Hyperbaric oxygenation (HBO) therapy has been shown to reduce mortality
      by 50% in a prospective randomized trial of severely brain injured patients
      conducted at the authors' institution. The purpose of the present study was to
      determine the effects of HBO on cerebral blood flow (CBF), cerebral metabolism,
      and intracranial pressure (ICP), and to determine the optimal HBO treatment
      paradigm. METHODS: Oxygen (100% O2, 1.5 atm absolute) was delivered to 37
      patients in a hyperbaric chamber for 60 minutes every 24 hours (maximum of seven
      treatments/patient). Cerebral blood flow, arteriovenous oxygen difference
      (AVDO2), cerebral metabolic rate of oxygen (CMRO2), ventricular cerebrospinal
      fluid (CSF) lactate, and ICP values were obtained 1 hour before and 1 hour and 6
      hours after a session in an HBO chamber. Patients were assigned to one of three
      categories according to whether they had reduced, normal, or raised CBF before
      HBO. In patients in whom CBF levels were reduced before HBO sessions, both CBF
      and CMRO2 levels were raised 1 hour and 6 hours after HBO (p < 0.05). In patients
      in whom CBF levels were normal before HBO sessions, both CBF and CMRO2 levels
      were increased at 1 hour (p < 0.05), but were decreased by 6 hours after HBO.
      Cerebral blood flow was reduced 1 hour and 6 hours after HBO (p < 0.05), but
      CMRO2 was unchanged in patients who had exhibited a raised CBF before an HBO
      session. In all patients AVDO2 remained constant both before and after HBO.
      Levels of CSF lactate were consistently decreased 1 hour and 6 hours after HBO,
      regardless of the patient's CBF category before undergoing HBO (p < 0.05).
      Intracranial pressure values higher than 15 mm Hg before HBO were decreased 1
      hour and 6 hours after HBO (p < 0.05). The effects of each HBO treatment did not
      last until the next session in the hyperbaric chamber. CONCLUSIONS: The increased
      CMRO2 and decreased CSF lactate levels after treatment indicate that HBO may
      improve aerobic metabolism in severely brain injured patients. This is the first
      study to demonstrate a prolonged effect of HBO treatment on CBF and cerebral
      metabolism. On the basis of their data the authors assert that shorter, more
      frequent exposure to HBO may optimize treatment.

PMID- 11235944
TI  - Determination of threshold levels of cerebral perfusion pressure and intracranial
      pressure in severe head injury by using receiver-operating characteristic curves:
      an observational study in 291 patients.
AB  - OBJECT: Intracranial pressure (ICP) and cerebral perfusion pressure (CPP) are
      frequently monitored in severely head injured patients. To establish which one
      (ICP or CPP) is more predictive of outcome and to examine whether there are
      significant threshold levels in the determination of outcome, receiver-operating
      characteristic (ROC) curves were used to analyze data in a large series of head
      injured patients. METHODS: Data were obtained from a total of 291 severely head
      injured patients (207 adults and 84 children). Outcome was categorized as either
      independent (good recovery or moderate disability) or poor (severely disabled,
      vegetative, or dead) by using the Glasgow Outcome Scale; patients were also
      grouped according to the Marshall computerized tomography scan classification.
      CONCLUSIONS: The maximum value of a 2-minute rolling average of ICP readings
      (defined as ICPmax) and the minimum value of the CPP readings (CPPmin) were then
      used to calculate the sensitivity and specificity of the ROC curves over a range
      of values. Using ROC curves, a threshold value for CPPmin of 55 mm Hg and for
      ICPmax of 35 mm Hg appear to be the best predictors in adults. For children the
      levels appear to be 43 to 45 mm Hg for CPPmin and 35 mm Hg for ICPmax. Higher
      levels of CPPmin seem important in adults with mass lesions. These CPP thresholds
      (45 mm Hg for children and 55 mm Hg for adults) are lower than previously
      predicted and may be clinically important, especially in children, in whom a
      lower blood pressure level is normal. Also, CPP management at higher levels may
      be more important in adults with mass lesions. A larger observational series
      would improve the accuracy of these predictions.

PMID- 11235945
TI  - Functional outcome after repair of unruptured intracranial aneurysms.
AB  - OBJECT: Repair of unruptured aneurysms is a reasonable course of action if their
      expected natural history is worse than the predicted risks of treatment. The
      purpose of this study was to examine the presenting symptoms of unruptured
      aneurysms and to test the hypothesis that unruptured intracranial aneurysms can
      be repaired without significant functional worsening. A second hypothesis was
      also examined--that is, that the experience of the surgeon, the aneurysm size,
      and the patient age can be used to predict functional outcome. METHODS:
      Consecutive patients who underwent repair of an unruptured intracranial aneurysm
      at a single institution between 1980 and 1998 were studied. Clinical and
      radiographic data were collected in all patients. Their modified Rankin Scale
      (mRS) score was determined before treatment (baseline), at 6 weeks, and at 6
      months. The primary endpoint for analysis was the mRS score. Four hundred forty
      nine aneurysms were repaired in 366 patients by 10 surgeons. The mean size of the
      primary lesion repaired was 14.6 + 10.4 mm and 27% were judged to be symptomatic.
      Aneurysm treatment involved either microsurgical clipping (78%), wrapping (4%),
      trapping with or without bypass (5%), hunterian ligation with or without bypass
      (9%), or other methods (4%). The mRS scores at 6 weeks were worse than at
      baseline (p < 0.0001), but there was no significant difference between the
      baseline and 6-month mRS score. At 6 months, 94% of patients showed no
      significant functional worsening as a result of treatment. The number of
      aneurysms treated by a specific surgeon was a strong predictor of better
      functional outcome (r = 0.99, p = 0.05). Increasing patient age (r = 0.16, p =
      0.003) and increasing aneurysm size (r = 0.15, p = 0.004) were predictors of
      worsened functional outcome. CONCLUSIONS: Many unruptured aneurysms produce
      symptoms. Unruptured intracranial aneurysms can be treated without significant
      permanent functional worsening. The surgeon's experience, aneurysm size, and
      patient age are predictors of functional outcome.

PMID- 11235946
TI  - Cerebellar hemorrhage caused by dural arteriovenous fistula: a review of five
      cases.
AB  - OBJECT: In this study the authors performed a retrospective analysis of five
      cases in which the patients (three women and two men) were treated for
      intracranial dural arteriovenous fistulas (AVFs) associated with cerebellar
      hemorrhage. On the basis of their findings, the authors evaluated the
      characteristics of this unusual symptom. METHODS: The dural AVFs were located in
      the right cavernous sinus in one patient, the left transverse-sigmoid sinus in
      three patients, and the right superior petrosal sinus (SPS) in one patient. All
      patients presented with severe headache and/or loss of consciousness.
      Computerized tomography scans revealed a small cerebellar hemorrhage near the
      fourth ventricle and hydrocephalus in four cases, and a massive hemispheric
      cerebellar hemorrhage in the remaining case. The four patients with small
      hemorrhages underwent ventriculostomy and endovascular treatment; all recovered.
      The patient suffering from a massive hemorrhage because of a dural AVF in the SPS
      was treated by suboccipital craniectomy, hematoma evacuation, and removal of the
      vascular anomaly. This patient remains in a persistent vegetative state. In four
      cases, results of angiography demonstrated retrograde leptomeningeal venous
      drainage through the SPS to the anastomotic lateral mesencephalic vein (ALMV)
      and/or to the vein of the lateral recess of the fourth ventricle (VLR4V).
      Retrograde leptomeningeal venous drainage to the ALMV and/or VLR4V was
      responsible for cerebellar hemorrhage in these cases. CONCLUSIONS: Thus, it is
      important to consider dural AVF in cases in which there is even a small
      hemorrhage near the fourth ventricle accompanied by intraventricular perforation
      and a decreased level of consciousness.

PMID- 11235947
TI  - Combined endovascular treatment of dissecting vertebral artery aneurysms by using
      stents and coils.
AB  - OBJECT: With the recent development and refinement of endovascular stents, the
      significant potential for these devices in the treatment of wide-necked
      dissecting and fusiform aneurysms has become apparent. In this article the
      authors report on the use of stents and coils to treat dissecting and fusiform
      vertebral artery (VA) aneurysms. METHODS: Eight consecutive patients harboring
      eight dissecting aneurysms and one fusiform aneurysm of the VA were succesfully
      treated using a procedure in which the authors inserted an intravascular stent
      and secondary endosaccular coils when needed. In all but one patient complete
      aneurysm occlusion was achieved, and in all cases there was no neurological
      complication. Follow-up angiography examinations were performed in all patients
      (mean duration of follow-up angiography review 13.1 months, range 3-42 months).
      The patients remained stable throughout the clinical follow-up period (mean 14.1
      months, range 4-42 months). No rebleeding was recorded. CONCLUSIONS: At present
      this combined approach represents a reliable and safe alternative for the
      treatment of VA dissecting aneurysms, especially in patients who cannot tolerate
      occlusion tests.

PMID- 11235948
TI  - Extent of tumor-brain interface: a new tool to predict evolution of malignant
      gliomas.
AB  - OBJECT: Tumor size is one of the features commonly used in oncology to predict
      disease evolution. However, for most primary brain tumors it is not predictive of
      outcome. Taking advantage of a gene therapy trial in which recurrences of
      glioblastoma were targeted with suicide genes, the authors developed a new
      parameter: the extent of tumor-brain interface--also called surface of tumor
      volume (STV)--to better describe three-dimensional conformation and the
      relationship between tumors and the surrounding normal tissue. Correlations
      between the STV and the usual clinical parameters were analyzed. METHODS: Between
      1995 and 1998, 16 patients presenting with recurrent glioblastomas were enrolled
      in this study. Preoperative magnetic resonance images were analyzed on a separate
      workstation; the interface between tumor and normal brain tissue was measured on
      each 3-mm-thick section to assess STV. The mean STV was 29.2 cm2, and the mean
      tumor volume (TV) was 23.8 cm3. The STV was significantly correlated with
      survival (Spearman test: r = -0.54, p = 0.03), but TV was not (Spearman test: r =
      -0.39, p = 0.15). A separate analysis of responding and nonresponding patients
      showed that, as expected, STV was negatively correlated with survival among
      nonresponding patients (p = 0.04), but that among responding patients there was a
      positive tendency between STV and survival. CONCLUSIONS: These findings indicate
      that STV may be a useful tool for predicting the evolution of malignant glioma.
      Moreover, in future gene therapy trials in which such in situ approaches are
      used, increasing density and improved distribution of transfer cells should be
      taken into consideration as an important issue for efficacy.

PMID- 11235949
TI  - Staged bilateral pallidotomy for treatment of Parkinson disease.
AB  - OBJECT: Several investigators have described the motor benefits derived from
      performing unilateral stereotactic pallidotomy for the treatment of Parkinson
      disease (PD), but little is known about the efficacy and complication rates of
      bilateral procedures. The goal of this study was to assess both these factors in
      12 patients. METHODS: Eleven patients with medically intractable PD underwent
      staged bilateral pallidotomy and one patient underwent a simultaneous bilateral
      procedure. Unilateral pallidotomy resulted in an improvement in the patients'
      Unified Parkinson Disease Rating Scale (UPDRS) total scores and motor subscores,
      Hoehn and Yahr stages, and Schwab and England Activities of Daily Living scores.
      There were no complications. The second procedures were performed 5 to 25 months
      after the first, and nearly complete 3-month follow-up data are available for
      eight of these patients. Staged bilateral pallidotomy did result in further
      improvements in some symptoms, but the patients proved to be less responsive to
      levodopa. In contrast to outcomes of the initial unilateral pallidotomy, there
      were significant complications. One patient suffered an acute stroke, two
      patients suffered delayed infarctions of the internal capsule, four patients had
      mild-to-moderate worsening of speech and increased drooling, and one patient
      complained of worsening memory. CONCLUSIONS: Bilateral pallidotomy results in
      modest benefits but is associated with an increased risk of complications.

PMID- 11235950
TI  - Magnetic source imaging of late evoked field responses to vowels: toward an
      assessment of hemispheric dominance for language.
AB  - OBJECT: The goal of this study was to determine whether the late neuromagnetic
      field elicited by simple speech sounds, which is detected by
      magnetoencephalography, may be used to estimate hemispheric dominance for
      language and to guide or constrain the intraoperative search for essential
      language sites. If sufficiently robust, a noninvasive method for assessing
      hemispheric dominance for language could reduce the necessity for amobarbital
      testing and the extent of intraoperative cortical stimulation-based mapping, both
      of which carry the risk of morbidity. METHODS: Fifteen patients undergoing
      surgery for tumors during which intraoperative language mapping would be
      performed and two additional patients in whom intracarotid amobarbital testing
      confirmed right-hemisphere language dominance participated. Following a primary
      auditory response sources of late neuromagnetic fields elicited by vowel stimuli
      were modeled and coregistered using magnetic resonance images to form magnetic
      source (MS) images. A laterality index (LI) was calculated by summing the number
      of equivalent current dipolar sources in the late fields detected from each
      hemisphere. In 14 right-handed patients, 10 displayed left asymmetric LIs (0.37
      +/- 0.16. mean +/- standard error of the mean in 14 patients). For both right
      hemisphere dominant patients in whom an LI was obtainable, the LI was rightward.
      Stimulation-mapped essential language sites were found in 7 of 15 patients. For
      six of these seven patients, the MS image-derived LI was leftward. CONCLUSIONS:
      Asymmetry in single equivalent dipole modeling of the late neuromagnetic field
      evoked by simple speech sounds correlates with hemispheric language dominance,
      although not to the degree necessary for individual clinical predictions. With
      further development, MS imaging of simple language tasks may be used
      preoperatively to predict language dominance and even to identify or constrain
      the intraoperative search for likely sites of essential language cortex.

PMID- 11235951
TI  - Bioabsorbable polymeric material coils for embolization of intracranial
      aneurysms: a preliminary experimental study.
AB  - OBJECT: A new embolic agent, bioabsorbable polymeric material (BPM), was
      incorporated into Guglielmi detachable coils (GDCs) to improve long-term
      anatomical results in the endovascular treatment of intracranial aneurysms. The
      authors investigated whether BPM-mounted GDCs (BPM/GDCs) accelerated the
      histopathological transformation of unorganized blood clot into fibrous
      connective tissue in experimental aneurysms created in swine. METHODS: Twenty
      four experimental aneurysms were created in 12 swine. In each animal, one
      aneurysm was embolized using BPM/GDCs and the other aneurysm was embolized using
      standard GDCs. Comparative angiographic and histopathological data were analyzed
      at 2 weeks and 3 months postembolization. At 14 days postembolization, angiograms
      revealed evidence of neck neointima in six of eight aneurysms treated with
      BPM/GDCs compared with zero of eight aneurysms treated with standard GDCs (p <
      0.05). At 3 months postembolization, angiograms demonstrated that four of four
      aneurysms treated with BPM/GDC were smaller and had neck neointima compared with
      zero of four aneurysms treated with standard GDCs (p = 0.05). At 14 days,
      histological analysis of aneurysm healing favored BPM/GDC treatment (all p <
      0.05): the grade of cellular reaction around the coils was 3 +/- 0.9 (mean +/-
      standard deviation) for aneurysms treated using BPM/GDCs compared with 1.6 +/-
      0.7 for aneurysms treated using GDCs alone; the percentage of unorganized
      thrombus was 16 +/- 12% compared with 37 +/- 15%, and the neck neointima
      thickness was 0.65 +/- 0.26 mm compared with 0.24 +/- 0.21 mm, respectively. At 3
      months postembolization, only neck neointima thickness was significantly
      different (p < 0.05): 0.73 +/- 0.37 mm in aneurysms filled with BPM/GDCs compared
      with 0.16 +/- 0.14 mm in aneurysms filled with standard GDCs. CONCLUSIONS: In
      experimental aneurysms in swine, BPM/GDCs accelerated aneurysm fibrosis and
      intensified neck neointima formation without causing parent artery stenosis or
      thrombosis. The use of BPM/GDCs may improve long-term anatomical outcomes by
      decreasing aneurysm recanalization due to stronger in situ anchoring of coils by
      organized fibrous tissue. The retraction of this scar tissue may also decrease
      the size of aneurysms and clinical manifestations of mass effect observed in
      large or giant aneurysms.

PMID- 11235952
TI  - Roles of membrane type 1 matrix metalloproteinase and tissue inhibitor of
      metalloproteinases 2 in invasion and dissemination of human malignant glioma.
AB  - OBJECT: Acquisition of invasive and metastatic potentials through proteinase
      expression is an essential event in tumor progression. Among proteinases, matrix
      metalloproteinases (MMPs) are thought to play a key role in tumor progression
      through the degradation of the extracellular matrix. In the present study, the
      authors examined the role of MMP-2 (gelatinase A) and membrane type 1 MMP (MT1
      MMP), an activator of the zymogen of MMP-2, proMMP-2, together with tissue
      inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in the invasion of
      astrocytic tumors in humans. METHODS: Analyses performed using sandwich enzyme
      immunoassays demonstrated that the production levels of pro-MMP-2 and TIMP-1, but
      not TIMP-2, are significantly higher in glioblastomas multiforme than in other
      grades of astrocytic tumors. Quantitative reverse transcription-polymerase chain
      reaction indicated that MT1-MMP is expressed predominantly in glioblastoma
      tissues, and its expression levels are significantly enhanced as tumor grade
      increases. In addition, the expression levels and proMMP-2 activation ratio were
      remarkably higher in glioblastomas associated with cerebrospinal fluid (CSF)
      dissemination than in those not associated with CSF dissemination. In contrast,
      an examination of TIMP-2 levels showed a reverse correlation. Like MT1-MMP, TIMP
      1 and TIMP-2 were immunolocalized to neoplastic cells in glioblastoma samples. To
      study the roles of these molecules in the invasion of astrocytic tumors more
      fully, stable transfectants expressing the MT1-MMP gene were developed in a U251
      human glioblastoma cell line. The MT1-MMP transfectants displayed prominent
      activation of proMMP-2 and invasive growth in three-dimensional collagen gel;
      however, mock transfectants and parental cells displayed noninvasive growth
      without the activation. The invasion and gelatinolytic activity of the
      transfectants were completely inhibited by addition of recombinant TIMP-2, but
      not recombinant TIMP-1. CONCLUSIONS: These results indicate that MT1-MMP may
      contribute to tumor invasion and CSF dissemination of glioblastoma cells on the
      basis of an imbalance of TIMP-2.

PMID- 11235953
TI  - Enhancement of antitumor immune response in glioma models in mice by genetically
      modified dendritic cells pulsed with Semliki forest virus-mediated complementary
      DNA.
AB  - OBJECT: The aim of this study was to further investigate dendritic cell (DC)
      based immunotherapy for malignant glioma to improve its therapeutic efficacy.
      METHODS: Dendritic cells were isolated from the bone marrow and pulsed with
      phosphate-buffered saline, tumor RNA, tumor lysate, Semliki Forest virus (SFV)
      LacZ, SFV-mediated B16 complementary (c)DNA, or SFV-mediated 203 glioma cDNA,
      respectively, to treat mice bearing tumors of the 203 glioma cell line. The
      results indicated that pre-immunization with DCs pulsed with the same type of
      cDNA as in the tumor by a self-replicating RNA vector (that is, SFV) protected
      mice from tumor challenge, and that therapeutic immunization prolonged the
      survival of mice with established tumors. The SFV induced apoptosis in DCs and
      their death facilitated the uptake of apoptotic cells by other DCs, thus
      providing a potential mechanism for enhanced immunogenicity. CONCLUSIONS: Therapy
      with DCs that have been pulsed with SFV-mediated tumor cDNA may be an excellent
      procedure for the development of new cancer vaccines.

PMID- 11235954
TI  - Age dependence of cerebrospinal pressure-volume compensation in patients with
      hydrocephalus.
AB  - OBJECT: The dynamics of both drainage and storage capacity become altered during
      the sequential pathological processes that lead to hydrocephalus. Cerebrospinal
      fluid (CSF) formation and drainage rate have been reported to be age dependent.
      The aim of this study was to investigate whether CSF compensatory parameters are
      dependent on age in patients who have symptoms of hydrocephalus and apparently
      normal intracranial pressure (ICP). METHODS: Forty-six patients who presented
      with ventriculomegaly, the clinical symptoms of hydrocephalus, and normal ICPs
      underwent a computerized CSF infusion test. Parameters used to describe CSF
      compensation were calculated and correlated with the age of each patient. The
      mean ICPs were found to be independent of the age of the patient. Resistance to
      CSF outflow (Rcsf), however, demonstrated a nonlinear increase with advancing age
      (r = -0.57; p < 0.0001) and was associated with a decrease in the CSF production
      rate, which also occurred with increasing age (r = 0.49; p < 0.002). Both the
      pulse amplitude of the ICP waveform and the slope of the amplitude-ICP regression
      line increased significantly with advancing age (r = 0.39; p < 0.01 and r = 0.43,
      p < 0.004, respectively). The nonlinear increase in the elastance coefficient
      indicated increasing brain stiffness, which acompanies older ages (r = -0.31; p <
      0.04). CONCLUSIONS: In a study of patients with symptoms of hydrocephalus, but
      normal ICPs, the increase in Rcsf and decrease in CSF production were most
      pronounced in patients who were older than 56 years of age. This relationship was
      more significant than previously suggested.

PMID- 11235955
TI  - Antitumor activity of the growth hormone receptor antagonist pegvisomant against
      human meningiomas in nude mice.
AB  - OBJECT: The authors have previously demonstrated that modulation of the growth
      hormone (GH)/insulin-like growth factor-I (IGF-I) axis can significantly affect
      meningioma growth in vitro. These studies were performed to evaluate the efficacy
      of GH receptor blockade in vivo. METHODS: Primary cultures from 15 meningioma
      tumors obtained in humans were xenografted into athymic mice. Approximately 1.5
      million cells from each of the 15 tumors were implanted into the flanks of two
      female mice, one pair for each tumor. One animal from each of the 15 pairs was
      then treated with the GH receptor antagonist pegvisomant and the other with
      vehicle alone for 8 weeks. The tumor volume was measured using digital calipers
      three times per week. The mean tumor volume at the initiation of injections was
      284 +/- 18.8 mm3 in the vehicle group and 291.1 +/- 20 mm3 in the pegvisomant
      group. After 8 weeks of treatment, the mean volume of tumors in the pegvisomant
      group was 198.3 +/- 18.9 mm3 compared with 350.1 +/- 23.5 mm3 for the vehicle
      group (p < 0.001). The serum IGF-I concentration in the vehicle group was 319 +/-
      12.9 microg/L compared with 257 +/- 9.7 in the pegvisomant group (p < 0.02). A
      small but significant decrease was observed in circulating IGF binding protein
      (IGFBP)-3 levels, whereas slight increases occurred with respect to serum IGFBP-1
      and IGFBP-4 levels. In the placebo group the tumor weight was 0.092 +/- 0.01 g
      compared with 0.057 +/- 0.01 g in the pegvisomant group (p < 0.02). The IGF-I and
      IGF-II concentrations were measured in the tumors by using a tissue extraction
      method. These human-specific immunoassays demonstrated that there was no
      autocrine production of IGF-I in any of the tumors, either in the pegvisomant or
      vehicle group. The IGF-I levels were highly variable (0-38.2 ng/g tissue) and did
      not differ significantly between treatment groups. CONCLUSIONS: In an in vivo
      tumor model, downregulation of the GH/IGF-I axis significantly reduces meningioma
      growth and, in some instances, causes tumor regression. Because the
      concentrations of IGF-II in tumor did not vary with pegvisomant treatment and
      there was no autocrine IGF-I production by the tumors, the mechanism of the
      antitumor effect is most likely a decrease of IGF-I in the circulation and/or
      surrounding host tissues. Because the authors have previously demonstrated that
      the GH receptor is ubiquitously expressed in meningiomas, direct blockade of the
      GH receptor on the tumors may also be contributing to inhibitory actions.

PMID- 11235956
TI  - Exacerbation of traumatically induced axonal injury by rapid posthypothermic
      rewarming and attenuation of axonal change by cyclosporin A.
AB  - OBJECT: Although considerable attention has been focused on the use of
      posttraumatic hypothermia, little consideration has been given to the issue of
      posthypothermic rewarming and its potentially damaging consequences. In this
      communication, the authors examine the issue of rapid posthypothermic rewarming
      compared with gradual rewarming while exploring the potential utility of
      cyclosporin A (CsA) administration for attenuating any rapid rewarming-induced
      axonal change. METHODS: Male Sprague-Dawley rats were subjected to impact
      acceleration injury and then their body temperature was lowered to 32 degrees C
      for 1 hour postinjury. After hypothermia, rewarming to normothermic levels was
      accomplished either within a 20-minute period (rapid rewarming) or over a 90
      minute period (slow rewarming). Some animals in the rapid rewarming group
      received intrathecal infusion of either CsA or its vehicle, whereas the rats in
      the slow rewarming group received vehicle alone. Both the CsA and its vehicle
      were administered immediately before initiation of rewarming. Twenty-four hours
      postinjury the animals' brains were processed for visualization of amyloid
      precursor protein (APP), a marker of traumatic axonal injury. The APP-positive
      axonal density in the gradually rewarmed group receiving vehicle was
      statistically significantly reduced in comparison with the rapidly rewarmed,
      vehicle-treated group. For the group undergoing rapid rewarming and treatment
      with CsA, a statistically significant reduction was also found in the density of
      the APP profiles compared with the rapidly rewarmed, vehicle-treated group.
      CONCLUSIONS: The results of this study show that rapid rewarming exacerbates
      traumatically induced axonal injury, which can be significantly attenuated by
      administering CsA.

PMID- 11235957
TI  - Diminution of metabolism/blood flow uncoupling following traumatic brain injury
      in rats in response to high-dose human albumin treatment.
AB  - OBJECT: The authors have recently demonstrated that high-dose human albumin is
      markedly neuroprotective in experimental traumatic brain injury (TBI) and
      cerebral ischemia. The pathophysiology of TBI involves acute uncoupling of
      cerebral glucose utilization and blood flow. The intent of this study was to
      establish whether the use of human albumin therapy in a model of acute TBI would
      influence this phenomenon. METHODS: Anesthetized, physiologically regulated rats
      received moderate (1.5-2 atm) fluid-percussion injury to the parietal lobe.
      Fifteen minutes after trauma or sham injury, rats in one group received human
      albumin (2.5 g/kg) administered intravenously and those in another group received
      0.9% saline vehicle. At 60 minutes and 24 hours posttrauma, autoradiographic
      studies of local cerebral blood flow (LCBF) and local cerebral glucose
      utilization (LCMRglu) were conducted, and the LCMRglu/LCBF ratio was determined.
      Sham-injured rats had normal levels of LCBF and LCMRglu, and no differences
      between vehicle- and albumin-treated rats were evident. Sixty minutes after TBI,
      LCBF was moderately reduced bilaterally in vehicle-treated rats, whereas in
      albumin-treated animals, the LCBF contralateral to the side of injury was
      generally normal. Despite acutely depressed LCBF, LCMRglu in vehicle-treated rats
      at 60 minutes was paradoxically normal bilaterally, and foci of elevated LCMRglu
      were noted in the ipsilateral hippocampus and thalamus. By contrast, in albumin
      treated rats studied 60 minutes post-TBI, reduced LCMRglu values were measured in
      the ipsilateral caudoputamen and parietal cortex, whereas LCMRglu in other
      ipsilateral and contralateral sites did not differ from that measured in sham
      injured animals. The metabolism/blood flow ratio was normal in sham-injured rats,
      but became markedly elevated in vehicle-treated rats 60 minutes post-TBI (on
      average, by threefold ipsilaterally and 2.1-fold contralaterally). By contrast,
      the mean metabolism/blood flow ratio in albumin-treated animals was elevated by
      only 1.6-fold ipsilaterally and was normal contralaterally. Twenty-four hours
      after TBI, LCBF contralateral to the side of injury had generally returned to
      normal levels in the albumin-treated group. CONCLUSIONS: These results
      demonstrate that human albumin therapy benefits the posttraumatic brain by
      diminishing the pronounced metabolism > blood flow dissociation that would
      otherwise occur within the 1st hour after injury. Viewed together with our
      previous evidence of histological neuroprotection, these findings indicate that
      human albumin therapy may represent a desirable treatment modality for acute TBI.

PMID- 11235958
TI  - Intractable epilepsy after a functional hemispherectomy: important lessons from
      an unusual case. Case report.
AB  - Residual seizures after functional hemispherectomy occur in approximately 20% of
      patients with catastrophic epilepsy. These episodes are traditionally attributed
      to incomplete disconnection, persistent epileptogenic activity in the ipsilateral
      insular cortex, or bilateral independent epileptogenic activity. The authors
      report on the case of an 8-year-old boy with an intractable seizure disorder who
      had classic frontal adversive seizures related to extensive unilateral left
      hemispheric cortical dysplasia. The initial intervention consisted of extensive
      removal of the epileptic frontal and precentral dysplastic tissue and multiple
      subpial transections of the dysplastic motor strip, guided by intraoperative
      electrocorticography, Subsequently, functional hemispherectomy including insular
      cortex resection was performed for persistent attacks. After a seizure-free
      period of 6 months, a new pattern ensued, consisting of an aura of fear, dystonic
      posturing of the right arm, and unusual postictal hyperphagia coupled with an
      interictal diencephalic-like syndrome. Electroencephalography and
      ictal/interictal single-photon emission computerized tomography were used to
      localize the residual epileptic discharges to deep ipsilateral structures.
      Results of magnetic resonance imaging indicated a complete disconnection except
      for a strip of residual frontobasal tissue. Therefore, a volumetric resection of
      the epileptogenic frontal basal tissue up to the anterior commissure was
      completed. The child has remained free of seizures during 21 months of follow-up
      review. Standard hemispherectomy methods provide extensive disconnection, despite
      the presence of residual frontal basal cortex. However, rarely, and especially if
      it is dysplastic, this tissue can represent a focus for refractory seizures. This
      is an important consideration in determining the source of ongoing seizures
      posthemispherectomy in patients with extensive cortical dysplasia. It remains
      important to assess them fully before considering their disease refractory to
      surgical treatment.

PMID- 11235959
TI  - Intracranial lipoma of the sylvian fissure. Case report and review of the
      literature.
AB  - The authors present a rare case of lipoma of the sylvian fissure found in a 34
      year-old man who presented with seizures. The patient underwent craniotomy and an
      attempted resection of the lesion, which was initially believed to be a dermoid
      tumor. The imaging characteristics of dermoids and lipomas are extremely similar.
      Given the difference in the natural history and resectability of these lesions,
      lipomas should be included in the differential diagnosis of lesions with imaging
      characteristics similar to dermoids. Currently, tumor location, density of the
      lesion or computerized tomography scans, and signal homogeneity of the lesion on
      magnetic resonance images can help one to distinguish these radiographically
      similar, but pathologically different, entities. As this case confirms, resection
      of a sylvian fissure lipoma is extremely difficult and potentially dangerous; in
      addition it is unlikely to improve symptoms. A short review of 10 cases reported
      in the literature and therapeutic options for these lesions are also discussed.

PMID- 11235960
TI  - Intrasellar cavernous hemangioma. Case report.
AB  - The authors present a rare entity, an intrasellar cavernous hemangioma that on
      neuroimages mimicked a nonfunctioning pituitary macroadenoma in a patient with a
      known orbital hemangioma. Such lesions can grow extraaxially within the dural
      sinuses, particularly the cavernous sinus, and present like tumors. A better
      understanding of the neuroimaging. clinical, and anatomical features of these
      lesions may prevent difficulties in management.

PMID- 11235961
TI  - Primary pineal melanocytic tumor. Case report.
AB  - A primary melanocytic lesion arising from the pineal gland is very rare. The
      authors report a case of primary pineal melanocytic tumor with dissemination to
      the right hippocampus in a 50-year-old woman who presented with memory
      disturbance. Magnetic resonance (MR) imaging revealed a mass that was
      hyperintense on T1-weighted and hypointense on T2-weighted MR images. The pineal
      tumor was removed subtotally via the occipital transtentorial approach, and the
      patient underwent whole-brain irradiation. Results of histological examination
      revealed that the tumor predominantly consisted of atypical cells with scanty
      melanin pigment and some necrotic foci. The strongly pigmented areas of the tumor
      contained well-differentiated cells similar to those of melanocytoma. An
      ultrastructural study demonstrated evidence of a mature type of melanosome. The
      patient died 11 months after surgery and radiotherapy (1.7 years after the onset
      of symptoms). The autopsy findings demonstrated tumor invasion into the
      parenchyma through the leptomeningeal space and the ventricular wall. The tumor
      was diagnosed as being malignant, and it was finally concluded that the atypical
      cells in the tumor were probably responsible. This pineal melanocytic tumor
      exhibited a wide spectrum of differentiation, ranging from highly malignant
      melanoma to well-differentiated melanocytoma, which may have contributed to the
      patient's relatively long survival period. The biological behavior and
      morphological characteristics of this tumor appear to be similar to those of
      other pineal parenchymal lesions.

PMID- 11235962
TI  - Cerebrospinal fluid immunocytochemical analysis and neuroimaging in the diagnosis
      of primary leptomeningeal melanoma. Case report.
AB  - A 20-year-old man presented with slowly progressing symptoms indicative of
      increased intracranial pressure. Two weeks later he underwent surgery for
      placement of a ventriculoperitoneal shunt. Cytological examination of the
      patient's cerebrospinal fluid (CSF) revealed atypical cells that contained no
      detectable melanin deposits, but proved to be immunocytochemically positive for
      monoclonal antibodies to melanocytic cells (HMB-45) and S-100 protein.
      Dermatological and ophthalmological examinations failed to demonstrate any
      abnormalities. On the basis of these findings, a diagnosis of primary
      leptomeningeal melanoma was made. Gadolinium-enhanced magnetic resonance (MR)
      images of the brain and spinal regions obtained 2 months after admission
      demonstrated typical widespread leptomeningeal enhancement. Results of technetium
      99m-hexakis (2-methoxyisobutyl isonitrile) single-photon emission computerized
      tomography (99mTc-MIBI SPECT) scanning revealed intense uptake of the isotope in
      the leptomeningeal regions and some cisterns. The patient's condition
      progressively worsened and he died 5 months after admission. The diagnosis was
      confirmed at autopsy. Immunocytochemical analysis of CSF performed using HMB-45
      and S-100 protein antibodies is important for the diagnosis of leptomeningeal
      melanoma because of the test's simplicity, high specificity, and sensitivity.
      Gadolinium-enhanced MR imaging is used to demonstrate the extent of the
      leptomeningeal melanoma. An additional and supplemental neuroimaging modality,
      99mTc-MIBI SPECT scanning has good potential for the detection and diagnosis of
      leptomeningeal melanoma.

PMID- 11235963
TI  - Developmental venous anomaly with an arteriovenous shunt and a thrombotic
      complication. Case report.
AB  - Developmental venous anomalies (DVAs) are common congenital variations of normal
      venous drainage that are known for their benign natural history. Isolated cases
      of symptomatic DVAs with associated arteriovenous (AV) shunts have recently been
      reported. The present case, in which thrombosis occurred in a DVA involving an AV
      shunt, raises intriguing questions regarding the clinical characteristics of
      these lesions and can be used to argue in favor of considering such lesions to be
      arteriovenous malformations (AVMs). A 39-year-old man presented with acute
      thrombosis in a complex system of anomalous hemispheric venous drainage, which
      included two distinct DVAs, one of which involved an AV shunt. The hemodynamic
      turbulences induced by a communication between shunted and normal venous outflows
      were the possible predisposing factor of the thrombosis. Follow-up angiographic
      and magnetic resonance images revealed complete recanalization of the thrombosed
      vessel and provided a thorough visualization of the particular angioarchitecture
      of the DVA. Acute thrombosis within a DVA with an AV shunt has not been reported
      previously and, thus, this case can be added to other reports of complications
      that arise in this particular type of DVA. The authors hypothesize that the
      presence of an AV shunt in a DVA is a risk factor for aggressive clinical
      behavior of the anomaly, rendering those lesions prone to complications similar
      to AVMs. Although no treatment can be offered, the presence of an AV shunt in a
      DVA warrants close follow-up observation because such lesions may represent a
      particular subtype of AVM and, therefore, may exhibit an aggressive clinical
      behavior.

PMID- 11235964
TI  - Lenticulostriate artery aneurysm in infancy. Case illustration.

PMID- 11235965
TI  - Retroclival craniopharyngioma. Case illustration.

PMID- 11235966
TI  - Brain-within-brain appearance of a heterotopic neuronal mass on magnetic
      resonance imaging. Case illustration.

PMID- 11235968
TI  - Mission possible.

PMID- 11235969
TI  - Bracing and reciprocation.

PMID- 11235967
TI  - Recurrent subarachnoid hemorrhage.

PMID- 11235970
TI  - Radiographic diagnosis of root resorption in relation to orthodontics.
AB  - The literature regarding external root resorption in relation to orthodontics and
      its radiographic diagnosis is reviewed, including a summary of the more common
      radiographic techniques available. Sample cases are presented which demonstrate
      the need for good radiographic technique and an awareness of the limitations of
      certain radiographs. A provisional diagnosis of external root resorption may need
      to be confirmed by further radiographic views where appropriate.

PMID- 11235971
TI  - Risky business.

PMID- 11235972
TI  - Dug-up roots.

PMID- 11235973
TI  - Therapists survey.

PMID- 11235974
TI  - CPR training.

PMID- 11235975
TI  - Changes in the percentage of 5-year-old children with no experience of decay in
      Dudley towns since the implementation of fluoridation schemes in 1987.
AB  - OBJECTIVE: To compare changes in dental health between non-fluoridated
      Stourbridge and the towns of Dudley, Sedgeley and Coseley, Brierley Hill and
      Kingswinford, and Halesowen that were artificially fluoridated in 1987. BASIC
      RESEARCH DESIGN: BASCD co-ordinated studies of total samples of 5-year-old
      children. CLINICAL SETTINGS: State funded primary schools in the Dudley Health
      Authority area. PARTICIPANTS: All 5-year-old children present on the day of
      examination in the years in which total population studies were conducted.
      INTERVENTIONS: Drinking water fluoridation commenced in 1987. MAIN OUTCOME
      MEASURE: The percentage of children with no experience of decay in their primary
      dentition. RESULTS: The percentage of children with no experience of decay in the
      fluoridated towns increased but remained the same in non-fluoridated Stourbridge.
      CONCLUSION: Drinking water fluoridation is associated with an increase in the
      percentage of 5-year-old children with no experience of tooth decay.

PMID- 11235976
TI  - Patients' pain experience following oral mucosal biopsy under local anaesthesia.
AB  - OBJECTIVE: To examine the incidence and severity of post-operative pain and use
      of analgesics following biopsy of oral mucosal lesions. DESIGN: A patient survey
      using a self-completed pain diary. SUBJECTS AND METHODS: Seventy-six patients
      attending an oral medicine clinic for investigation of oral mucosal disease
      recorded overall and worst pain experiences and analgesic usage over 7 post
      operative days following biopsy using visual analogue scales in patient completed
      diaries. RESULTS: One third of patients reported no post-operative pain on any
      day. Most patients recorded no pain or mild pain. The percentage experiencing
      pain dropped from the first day (61%) to the seventh day (21%). Most patients did
      not use any analgesics. Analgesic use was not related to the presence of pain.
      Only a small minority of patients recorded severe pain. CONCLUSION: Biopsy of
      oral mucosal lesions does not cause undue pain in most patients.

PMID- 11235977
TI  - Management information failings and future requirements for dental commissioning
      groups.
AB  - OBJECTIVE: To examine existing secondary care management information systems for
      dental specialities, and to determine their completeness and suitability for
      supporting effective primary care led purchasing decisions. DESIGN: An
      observational cross-sectional study of current information systems in selected
      secondary care provider units and the applicability of their data for contracting
      dental services. A comparative study of two information systems in two settings
      (primary and secondary care) and the utility of the data gathered for contracting
      for dental services. SUBJECTS: Secondary care activity data was sought from the
      key secondary dental care providers (hospitals) in two dental total purchasing
      localities. Referral data were also collected directly from general dental
      practitioners. MAIN OUTCOME MEASURES: The integrity, quality and accuracy of
      current secondary care activity data in dental specialities, in comparison to
      data supplied from primary dental care. RESULTS: The secondary care activity data
      was found to be incomplete, inadequate and inaccurate. It was found that due to
      data retrieval insufficiency, indicative budgets for secondary providers may be
      reduced to less than half of their actual entitlement. The data inflated
      individual dental outpatient attendance by 3.3 times between 1995/6 and by 2.5
      times between 1996/7. CONCLUSION: Existing management information systems within
      secondary care providers are not structured in a way which will adequately inform
      future commissioning by the dental profession. Communication between primary and
      secondary care must be increased and data inputting methods in secondary care
      provider units must be substantially improved.

PMID- 11235978
TI  - Dental restorations in adults in the UK in 1998 and implications for the future.
AB  - People in their late fifties in the UK today can expect to live another 20 years
      and most want to maintain a functional and aesthetically acceptable dentition.
      However, 50% of the teeth of dentate adults aged 45 years and over are filled and
      crowned. The challenges for the dental profession in addressing these aspirations
      are discussed.

PMID- 11235979
TI  - The development of an assessment system for dental vocational training and
      general professional training: a Scottish approach.
AB  - The role of competencies in postgraduate dental education and training has been a
      major topic of interest in recent years. Concerns have been voiced from all sides
      of the profession about how the competence of trainees and the quality of
      training can be assured so that high standards of patient care can be maintained.
      A three year project which seeks to develop a competency-based assessment system
      for general professional training is underway which hopes to answer some of the
      concerns and provide an evidence-based system of assessment for the early
      postgraduate years. This paper looks at the reasoning behind the project, its
      aims, and the progress made to date.

PMID- 11235980
TI  - Just say 'no'.

PMID- 11235981
TI  - A study of the genetic and environmental etiology of stuttering in a selected
      twin sample.
AB  - Stuttering is a developmental disorder of speech production that usually emerges
      in childhood. In this study, a large population-based twin sample from the
      Australian Twin Registry (1567 pairs and 634 singles aged 17-29 years) was
      screened to identify twin pairs in which one or both members reported themselves
      to be affected by stuttering. Telephone interview-based diagnoses were obtained
      for 457 of these individuals (self-reported affected cases, cotwins, and
      controls) to determine whether the self-report was correct. To correct for
      ascertainment bias we carried out a bivariate analysis of the final diagnosis in
      the selected sample with the screening item in the full sample, using the
      categorical raw data option of Mx 1.47c. After correcting for ascertainment bias,
      approximately 70% (95% confidence interval: 39-86%) of the variance in liability
      to stuttering was found to be attributable to additive genetic effects, with the
      remainder due to nonshared environmental effects.

PMID- 11235982
TI  - Loss of aggression, after transfer onto a C57BL/6J background, in mice carrying a
      targeted disruption of the neuronal nitric oxide synthase gene.
AB  - Phenotypic differences among mice with disrupted genes and those with wild-type
      alleles have not provided the necessary evidence for desired gene/phenotype
      correlations. These differences could be due to "passenger genes" from the donor
      129 strains that are used to produce stem cells. Three variations of attack
      behavior were measured, using mice carrying a disruption of the neural nitric
      oxide synthase gene. In the first population, the disrupted gene had been
      maintained on a mixed background including C57BL/6J and 129 alleles. We have
      developed a second population in which the disrupted gene was transferred onto a
      C57BL/6J background during five backcross generations. On the mixed C57BL/6J-129
      background, mice homozygous for disrupted Nos1 alleles attacked more frequently,
      had shorter attack latencies, and presented a greater number of attacks than mice
      carrying nondisrupted alleles. On the C57BL/6J background, no significant
      difference persisted between the carriers of the disrupted gene and their
      noncarrier siblings. The noncarriers on the mixed C57BL/6J-129 background, and
      the carriers or noncarriers on the C57BL/6J background, did not differ from
      C57BL/6J. The frequency of attacking males was identical in the homozygous
      carriers of the disrupted gene, in the mixed C57BL/6J-129 background, and in the
      129/SvPas, which approximates the 129/SvJae strain from which the stem cells were
      derived to produce the disrupted Nos1 gene. These results suggest that Nos1
      disruption was not implicated in attack behavior. A possible passenger-gene
      effect from the 129 donor strain is discussed.

PMID- 11235983
TI  - A comparative study of the behavioral patterns of RLA/Verh and RHA/Verh rats in
      the exploration box.
AB  - Roman high- and low-avoidance (RHA/Verh and RLA/Verh) rats differ in their
      emotionality profiles. As emotional processes are considered to play an important
      role in exploratory behavior, differences between the Roman sublines in
      responding to a novel environment can be anticipated. The present study provides
      a quantitative (based on the frequency of particular responses) and qualitative
      (based on the frequency of behavioral sequences) comparison of exploratory
      behavior of RHA/Verh and RLA/Verh rats. Rats of both sexes were tested
      individually for 30 min in an exploration box containing a few objects.
      Observation periods were divided, based on earlier studies, into three
      consecutive blocks of 5, 10, and 15 min, respectively. Analysis of quantitative
      data showed differences in sniffing (RHA/Verh scoring higher) and in immobility
      (RLA/Verh scoring higher), both persisting throughout all measurement periods.
      Males of both sublines were generally more active and exploratory than their
      respective females. The analysis of sequential data revealed that during the
      first 5 min RHA/Verh rats showed a less diverse but more exploratory repertoire
      and that during the first 15 min males of both sublines showed more behavioral
      sequences than females. This study indicates that the Roman rat sublines should
      provide a useful model to study the mechanisms of exploratory behavior.

PMID- 11235984
TI  - Familial aggregation of dyslexia phenotypes.
AB  - There is evidence for genetic contributions to reading disability, but the
      phenotypic heterogeneity associated with the clinical diagnosis may make
      identification of the underlying genetic basis difficult. In order to elucidate
      distinct phenotypic features that may be contributing to the genotypic
      heterogeneity, we assessed the familial aggregation patterns of Verbal IQ and 24
      phenotypic measures associated with dyslexia in 102 nuclear families ascertained
      through probands in grades 1 through 6 who met the criteria for this disorder.
      Correlations between relatives were computed for all diagnostic phenotypes, using
      a generalized estimating equation (GEE) approach. GEE is a recently developed
      semiparametric method for handling correlated data. The method is robust to model
      misspecification and flexible in adjusting for the subjects' characteristics and
      pedigree sizes as well as for the ascertainment process, while estimating the
      correlations between related subjects. The Nonword Memory (NWM) subtest of a
      prepublication version of the Comprehensive Test of Phonological Processing
      (CTOPP) and Phonemic Decoding Efficiency (PDE) subtest of a prepublication
      version of the Test of Word Reading Efficiency (TOWRE) showed correlation
      patterns in relatives that are strongly supportive of a genetic basis. The
      Wechsler Scale Digit Span, the Word Attack subtest of the Woodcock Reading
      Mastery Test--Revised, and the Spelling subtest of the Wide Range Achievement
      Test--Third Edition had slightly weaker evidence of a genetic basis. Five
      additional phenotypes (the Spelling subtest of the Wechsler Individual
      Achievement Test, the Accuracy, Rate, and Comprehension subtests of the Gray Oral
      Reading Test--Third Edition, and Rapid Automatized Naming of Letters and Numbers)
      gave suggestive evidence of such a pattern. The results cross-validate in that
      evidence for a pattern consistent with a genetic basis was obtained for two
      measures of phonological short-term memory (CTOPP Nonword Memory and WISCIII or
      WAIS-R Digit Span), for two measures of phonological decoding (WRMT-R Word Attack
      and TOWRE Phonemic Decoding Efficiency), and for two measures of spelling from
      dictation (WRAT-3 Spelling and, to a lesser extent, WIAT Spelling). These
      measures are thus good candidates for more sophisticated segregation analyses
      that can formulate models for incorporation into linkage analyses.

PMID- 11235985
TI  - VIIIth International Congress of the Metastasis Research Society.

PMID- 11235986
TI  - Tissue inhibitors of metalloproteases: regulation and biological activities.
AB  - A central role in tissue invasion is played by proteases that degrade
      extracellular matrices; in particular specific metalloproteases (MMPs) have been
      frequently correlated with the invasive potential of tumor cells and with the
      angiogenic process. MMPs are tightly regulated by molecules controlling their
      activation and by specific inhibitors of MMPs, known as the Tissue Inhibitors of
      MetalloProteases or TIMPs. Four TIMP family members are currently known. An
      imbalance between MMPs and TIMPs is linked to the degradation of the
      extracellular matrix associated with several physiologic and pathologic events
      including angiogenesis, invasion and metastasis. TIMPs are not only the
      'guardians' of tissue degradation, they are able to control cell proliferation
      and cell survival as well. Given the critical role that TIMPs play, it is vital
      to know how the expression of TIMPs is controlled. Here we review the major
      biological properties and the molecular regulation of the TIMP expression.

PMID- 11235987
TI  - Antioxidants inhibit TNFalpha-induced motility and invasion of human osteosarcoma
      cells: possible involvement of NFkappaB activation.
AB  - Osteosarcoma is the most frequent malignant bone tumor in children. It is highly
      invasive, however, the mechanisms behind osteosarcoma cell invasion are as yet
      still unknown. In the present study, treatment with TNFalpha enhanced the
      invasiveness of two human osteosarcoma cell lines, OST and MNNG. TNFalpha
      treatment also induced tumor cell motility, adhesion to laminin, the expression
      of matrix metalloproteinase 9 (MMP9), and the nuclear translocation of nuclear
      factor kappaB (NFkappaB) in the osteosarcoma cells. Moreover, antioxidants
      inhibited TNFalpha-induced osteosarcoma cell invasion, motility and NFkappaB
      nuclear translocation, but not adhesion to laminin or MMP9 expression. NFkappaB
      decoy, another NFkappaB inhibitor, also inhibited TNFalpha-induced osteosarcoma
      cell invasion and motility. Therefore, motility and NFkappaB activation were
      possibly related to TNFalpha-induced osteosarcoma cell invasion. However,
      adhesion to laminin or MMP did not demonstrate any correlation with TNFalpha
      induced osteosarcoma cell invasion. Although NFkappaB is known to regulate
      TNFalpha-induced phenotypes, it may influence only motility and invasion, but not
      the MMP or laminin-mediated adhesion of these osteosarcoma cells.

PMID- 11235988
TI  - Heat shock-mediated transient increase in intracellular 3',5'-cyclic AMP results
      in tumor specific suppression of membrane type 1-matrix metalloproteinase
      production and progelatinase A activation.
AB  - We have previously reported that heat shock suppresses the production and gene
      expression of membrane type 1-matrix metalloproteinase (MT1-MMP) and thereby
      inhibits the activation of progelatinase A/proMMP-2 in human fibrosarcoma HT-1080
      cells and human squamous carcinoma A431 cells and SAS cells (Sato et al. Biochem
      Biophys Res Commun 1999; 265: 189-93). In an effort to clarify the heat shock
      mediated signal transduction pathways, an intracellular cAMP level was found to
      be transiently augmented in the heat shocked HT-1080 cells. When HT-1080 cells
      were pretreated with cAMP elevating reagents, forskolin and dibutyryl cAMP for 4
      h instead of heat shock and then maintained in a fresh medium, the production and
      gene expression of MT1-MMP were similarly suppressed. The MT1-MMP-mediated
      activation of proMMP-2 was also inhibited in the forskolin- and dibutyryl cAMP
      treated HT-1080 cells. Furthermore, the transiently augmented cAMP by forskolin
      as well as heat shock interfered with in vitro invasive activity of HT-1080
      cells. In contrast, in normal human fibroblasts neither heat shock nor cAMP
      elevating reagents altered the concanavalin A-augmented MT1-MMP production and
      proMMP-2 activation. These results suggest that a transient increase in
      intracellular cAMP is a critical signal for heat shock to induce tumor specific
      suppression of MT1-MMP production and proMMP-2 activation.

PMID- 11235989
TI  - Influence of chemically modified tetracyclines on proliferation, invasion and
      migration properties of MDA-MB-468 human breast cancer cells.
AB  - Chemically modified tetracyclines (CMTs) are promising anti-cancer agents. In
      this study, we found that CMT-3 and CMT-8 showed dose-dependent cytotoxicities in
      MDA-MB-468 human breast cancer cells. Moreover, both CMT-3 and CMT-8
      significantly inhibited in vitro cell migration and invasion at non-cytotoxic
      concentrations. Anti-invasion and migration potentials of the CMTs were
      associated with an increased expression of E-cadherin/catenins (alpha, beta and
      gamma-catenin) and tumor suppressor BRCA1. In addition, CMT-3 and CMT-8 abolished
      or reduced spontaneous and HGF/SF-induced cell invasion and migration in U-373 MG
      human glioblastoma cells. Our current finding is the first demonstration that CMT
      3 and CMT-8 can activate the function of invasion suppressor molecules associated
      with the suppression of breast cancer cell invasion and migration. Thus, clinical
      application of CMTs may provide potential benefit for suppression of breast
      cancer growth, invasion and metastasis.

PMID- 11235990
TI  - Potentiation of antitumor effect of NKT cell ligand, alpha-galactosylceramide by
      combination with IL-12 on lung metastasis of malignant melanoma cells.
AB  - The combined therapeutic effect of natural killer T (NKT) cell ligand alpha
      galactosylceramide (alpha-GalCer) and IL-12 against highly metastatic B16-BL6-HM
      melanoma cells was investigated. In comparison with a single administration of
      alpha-GalCer or IL-12, the combined treatment of tumor-bearing mice with alpha
      GalCer plus IL-12 caused a super-induction of serum IFN-gamma levels, though
      alpha-GalCer-induced IL-4 production was rather inhibited. In parallel with the
      augmented IFN-gamma production, the natural killing activity against YAC-1 cells
      and syngeneic B16-BL6-HM melanoma was greatly augmented by the combined therapy.
      The major effector cells responsible for natural killing activity induced by
      alpha-GalCer plus IL-12 were enriched in both NK1.1+ TCRalphabeta+ NKT cells and
      NK1.1+ TCRalphabeta- NK cells. The preventing effect of alpha-GalCer or IL-12
      alone against lung metastasis of B16-BL6-HM was also enhanced by the combination
      therapy. The antitumor activity of alpha-GalCer was totally abolished in NKT
      deficient mice. However, IL-12-induced antitumor activity was not eliminated in
      NKT-deficient mice though it was inhibited by anti-asialo GM1 Ab treatment. These
      findings suggested that alpha-GalCer synergistically act with IL-12 to activate
      both NKT cells and NK cells, which may play a critical role in the strong
      prevention of distant tumor metastasis at early stages of tumor-bearing. These
      data will provide a novel tool for the prevention of tumor metastasis using NKT
      specific ligands alpha-GalCer and IL-12.

PMID- 11235991
TI  - Vascular endothelial growth factor family members are differentially regulated by
      c-erbB signaling in head and neck squamous carcinoma cells.
AB  - Aberrant expression of tyrosine kinases such as c-erbB and EGFR contributes to
      the progression of head and neck squamous cell carcinomas (HNSCCs). One mechanism
      may be potentiation of angiogenesis, since upregulation of vascular endothelial
      growth factor (VEGF) expression by activation of epidermal growth factor receptor
      (EGFR) and/or c-erbB-2 has been described. Firstly, we demonstrated expression of
      all 4 members of the VEGF family in a panel of 15 HNSCC cell lines which over
      express one or more c-erbB receptors. We then explored the regulatory roles of
      three major ligands with different selectivity of binding to c-erbB receptors
      (namely transforming growth factor-alpha (TGF-alpha), betacellulin (BTC) and
      heregulin-beta1 (HRG-beta1)) on VEGF-A, B, C and D expression in selected HNSCC
      lines. Using semi-quantitative reverse transcription-PCR, we showed that all
      three c-erbB ligands up-regulated VEGF-A mRNA (all isoforms) and VEGF-C (BTC max
      at 1-10 nM; TGF-alpha and HRG-beta1 max at 10-100 nM) but had no effect on VEGF
      B. Interestingly, all ligands simultaneously down-regulated the expression of
      VEGF-D mRNA. A monoclonal antibody (mAb) which blocks EGFR ligand binding (ICR62)
      down-regulated the basal levels of VEGF-A (all isoforms) and VEGF-C, had no
      detectable effects on VEGF-B and increased VEGF-D. ICR62 also reversed the
      effects of all three erbB ligands (TGF-alpha, BTC and HRG-beta1) on VEGF-A, VEGF
      C and VEGF-D expression. An anti-c-erbB-2 mAb (ICR12) showed similar effects on
      basal or ligand-modulated expression of VEGF in these cell lines, although to a
      lesser extent. Our results reveal that the four VEGF genes are regulated by c
      erbB signaling pathways in a strikingly different manner, suggesting that they
      serve distinct, although perhaps complimentary (VEGF-A and VEGF-C) or
      antagonistic (VEGF-D) functions. The EGFR and c-erbB-2 signaling pathway(s) plays
      a role in VEGF regulation in HNSCC, although EGFR would appear to be dominant in
      this cell type.

PMID- 11235992
TI  - Vesicle-associated urokinase plasminogen activator promotes invasion in prostate
      cancer cell lines.
AB  - The ability of a cell to modify the extracellular matrix is important in several
      pathophysiological alterations including tumorigenesis. Cell transformation is
      accompanied by changes in the surrounding stroma as a result of the action of
      specific proteases such as the urokinase plasminogen activator (uPA), which has
      been associated with invasive potential in many tumor types. In this study, we
      analyzed the release of vesicle-associated uPA by the aggressive prostatic
      carcinoma cell line PC3 and the implications of this release for the invasive
      behaviour of prostatic tumor cells. Zymography and Western blot analysis revealed
      the presence of vesicle-associated uPA in the high-molecular weight form.
      Vesicles adhered to and degraded both collagen IV and reconstituted basal
      membrane (Matrigel), and plasminogen enhanced the degradation in a dose-dependent
      manner. Addition of membrane vesicles shed by PC3 cells to cultures of the poorly
      invasive prostate cancer cell line LnCaP enhanced the adhesive and invasive
      capabilities of the latter, suggesting a mechanism involving substrate
      recognition and degradation. Together, these findings indicate that membrane
      vesicles can promote tumor invasion and point to the important role of vesicle
      associated uPA in the extracellular compartment.

PMID- 11235993
TI  - Specific expression of matrix metalloproteinases 1, 3, 9 and 13 associated with
      invasiveness of breast cancer cells in vitro.
AB  - Several matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs)
      were studied in highly invasive (MDA-MB-231) and slightly invasive (MCF-7, T47D,
      BT-20) breast cancer cell lines. Investigations were carried out at the protein
      level and/or at the mRNA level, either in cells cultured as monolayers on
      plastic, or in cells seeded on a thin layer of Matrigel basement membrane matrix.
      Analysis of MMP expression by RT-PCR showed expression of MMP-1. MMP-3, and MMP
      13 in highly invasive MDA-MB-231 cells, but not in slightly invasive cell lines.
      The extracellular secretion of MMP-1 and MMP-3 by MDA-MB 231 cells could be also
      shown by ELISA. TIMP-1 and TIMP-2 mRNAs were found in all cell lines, however,
      the extracellular secretion of both TIMPs was much higher in MDA-MB-231 cells
      than in the other cell lines. When the cells were cultured on Matrigel matrix,
      MMP-9 expression was induced in MDA-MB-231 cells only, as assessed by RT-PCR and
      zymography experiments. The invasive potential of MDA-MB-231 cells evaluated in
      vitro through Matrigel was significantly inhibited by the MMP inhibitor BB-2516,
      by 25% and 50% at the concentrations of 2 x 10(-6) M and 10(-5) M, respectively.
      In conclusion, our data show that highly invasive MDA-MB-231 cells but not
      slightly invasive T47D, MCF-7 and BT-20 cells express MMP-1, MMP-3, MMP-9 and MMP
      13. MMP-9 which is specifically up-regulated by cell contact to Matrigel, may
      play a key role in the invasiveness of MDA-MB-231 cells through basement
      membranes.

PMID- 11235995
TI  - The microscopic anatomy of experimental rat CC531 colon tumour metastases:
      consequences for immunotherapy?
AB  - The colon adenocarcinoma cell line CC531 was adopted as a model for
      immunotherapeutical treatment of experimental colorectal metastases in a
      syngeneic rat model. We studied the presence and localization of T and natural
      killer cells, vessels and matrix proteins in in vivo growing CC531 tumours by
      immunohistochemistry. CC531 tumours were induced either in the lungs by injecting
      CC531 tumour cells into a tail vein or in the liver by injection of CC531 tumour
      cells under the liver capsule or into a mesenteric vein. All 3 tumour types were
      composed of islets of tightly apposed tumour cells surrounded by abundantly
      present tumour-stroma which contained tumour vessels and matrix proteins. Some of
      these matrix proteins, especially laminin and collagen IV formed a basal membrane
      like structure around the tumour nodules. This structure was most pronounced in
      mesenteric vein-induced liver tumours and less prominent in subcapsular-induced
      liver tumours and tail vein-induced lung tumours. Tumour-infiltrating lymphocytes
      of both T and natural killer cell origin were found in the tumours, but
      predominantly in the tumour stroma, separated from the islets of tumour cells by
      the basal membrane-like structure. We hypothesize that the matrix proteins of
      these tumours play an ambivalent role: they may provide a substratum for
      migration of effector cells into the tumour stroma but may also provide a barrier
      preventing direct contact between tumour target cells and immune effector cells.

PMID- 11235994
TI  - Enhanced production and activation of progelatinase A mediated by membrane-type 1
      matrix metalloproteinase in human oral squamous cell carcinomas: implications for
      lymph node metastasis.
AB  - We measured the production levels of seven different matrix metalloproteinases
      (MMP-1, 2, 3, 7, 8, 9 and 13) and two tissue inhibitors of metalloproteinases
      (TIMP-1 and 2) in the homogenates of human oral squamous cell carcinomas and
      control normal squamous epithelia by the corresponding sandwich enzyme
      immunoassay systems. The levels of MMP-1, 2, 3, 8, 9, 13 and TIMP-1 were
      significantly higher in the carcinoma samples than in the control. Among them,
      only the production level of MMP-2 was significantly higher in the carcinomas
      with cervical lymph node metastasis than in those without metastasis (P < 0.05).
      Gelatin zymography demonstrated that activation ratio of the zymogen of MMP-2
      (proMMP-2) is significantly higher in the carcinomas with lymph node metastasis
      than in those without metastasis (P < 0.05) or normal control (P < 0.01).
      Quantitative RT-PCR for membrane-types 1, 2 and 3 MMPs (MT1, 2 and 3-MMPs), which
      activate proMMP-2 in vitro, demonstrated that MT1-MMP is predominantly expressed
      in the carcinoma tissues, and the expression level is significantly higher in the
      carcinomas with lymph node metastasis than in those without metastasis (P < 0.05)
      or the control samples (P < 0.05). Although MT2-MMP and MT3-MMP were detected in
      approximately 30% of the carcinoma cases, their expression levels were extremely
      lower compared with that of MT1-MMP. There was a direct correlation between the
      MT1-MMP expression level and proMMP-2 activation ratio (r = 0.62, P < 0.01). In
      situ hybridization and immunohistochemistry indicated that carcinoma cells and
      stromal cells adjacent to carcinoma cell nests express MT1-MMP transcripts and
      protein. MMP-2 and TIMP-2 were also immunolocalized to the carcinoma cells in the
      carcinoma samples. By in situ zymography, gelatinolytic activity was demonstrated
      in the carcinoma cell nests and abolished by the treatment with an MMP inhibitor,
      BB94. These results suggest that among seven different MMPs, the production of
      proMMP-2 and its activation mediated by MT1-MMP play an important role in the
      cervical lymph node metastasis of the human oral squamous cell carcinomas.

PMID- 11235996
TI  - Expression of CD44 in effusions of patients diagnosed with serous ovarian
      carcinoma--diagnostic and prognostic implications.
AB  - CD44 is a family of cell adhesion molecules involved in a variety of cellular
      functions. The present study analysed the expression of two CD44 isoforms in
      serous effusions of patients diagnosed with ovarian carcinoma and corresponding
      primary and metastatic lesions. Fifty-eight effusions, 23 primary ovarian
      tumours, and 44 metastatic lesions were studied for protein expression of CD44s
      and v3-10 using immunohistochemistry. Results were correlated with clinical
      parameters. CD44v3-10 was seen in carcinoma cells in the majority of cases at all
      sites. Malignant effusions showed an up-regulation of CD44s compared to both
      primary tumours and metastatic solid lesions. Mesothelial cells frequently
      expressed CD44s, but were rarely immunoreactive for v3-10. CD44s immunoreactivity
      in cancer cells in effusions was significantly more often observed in patients
      with FIGO stage 3 than in stage 4 patients (P = 0.045). Staining results did not
      correlate with age, effusion site, metastatic site, tumour grade or residual
      tumour mass after initial surgery. Likewise, comparison of overall and disease
      free survival with expression of the CD44 isoforms studied did not reveal any
      statistically significant associations. The up-regulation in CD44 levels in
      effusions, primarily in stage 3 disease, suggests that adhesion of ovarian
      carcinoma cells to mesothelium may be regulated at the level of CD44s expression,
      and provides further evidence of phenotypic alteration in the transition from
      primary tumour cell clones to effusions. The similar expression profile of CD44
      in carcinoma cells in peritoneal and pleural effusions supports our previous
      observations and the hypothesis that carcinoma cells in peritoneal effusions are
      truly metastatic.

PMID- 11235997
TI  - Localization of glutamate receptors at a complex synapse. The mammalian
      photoreceptor synapse.
AB  - A key feature of signal processing in the mammalian retina is parallel
      processing, where the segregation of visual information, e.g., brightness,
      darkness, and color, starts at the first synapse in the retina, the photoreceptor
      synapse. These various aspects are transmitted in parallel from the input neurons
      of the retina, the photoreceptor cells, through the interconnecting bipolar
      cells, to the output neurons, the ganglion cells. The photoreceptors and bipolar
      cells release a single excitatory neurotransmitter, glutamate, at their synapses.
      This parsimony is contrasted by the expression of a plethora of glutamate
      receptors, receptor subunits, and isoforms. The detailed knowledge of the
      synaptic distribution of glutamate receptors thus is of major importance in
      understanding the mechanisms of retinal signal processing. This review intends to
      highlight recent studies on the distribution of glutamate receptors at the
      photoreceptor synapses of the mammalian retina.

PMID- 11235998
TI  - Synthesis and localization of the mucin-associated TFF-peptides in the human
      uterus.
AB  - TFF-peptides (formerly P-domain peptides, trefoil factors) are typical secretory
      products of mucin-producing cells and are thought to influence the rheological
      properties of mucous gels. Here, the localization of these peptides in the human
      uterus was investigated. An analysis of TFF-peptides mRNA by the polymerase chain
      reaction revealed TFF3 mainly in the endocervix and smaller amounts in the
      endometrium. TFF1 and TFF2 mRNA was detectable occasionally in the endocervix and
      very rarely in the endometrium. Western blot analysis detected only TFF3 in
      tissue extracts of the endocervix and as a constituent of human cervical mucus.
      Immunofluorescence localized TFF3 in the surface epithelium of the endocervix and
      in gland-like structures of the cervical epithelium.

PMID- 11235999
TI  - A scanning electron-microscopic study of apical contacts in the eye during
      postembryonic development of Drosophila melanogaster.
AB  - The apical surface of the ommatidium plays a major role during development of the
      compound eye. Cell-cell contacts leading to induction seem to be initiated at
      this surface. The pupal eye of Drosophila was examined, using scanning electron
      microscopy, from a few hours after eversion of the imaginal disc (19 h after
      pupariation, 25 degrees C) until shortly after the onset of the corneal secretion
      (46 h after pupariation, 25 degrees C). At 19 h, the primary pigment cells are in
      the process of encircling the cone cells. At this time, tufts formed by the cone
      cell microvilli are the most prominent feature of the eye's surface. Shortly
      thereafter, the interommatidial cells become more prominent. Their surfaces are
      raised to form ridges that enclose primary pigment cells and cone cells. From 21
      h onwards and lasting for 5-6 h, the interommatidial cells form slim cytoplasmic
      extensions that spread over the surfaces of the surrounding cells. These
      extensions contact neighbouring interommatidial or primary pigment cells, but
      also non-adjacent cells such as cone cells. The fates of these interommatidial
      cells presumably are determined during that time. The cell-cell interactions may
      play a role in determining cell fates, for example by providing positional
      information.

PMID- 11236000
TI  - Bacterial expression of the shrimp molt-inhibiting hormone (MIH): antibody
      production, immunocytochemical study and biological assay.
AB  - Molting in shrimp is controlled by the molt-inhibiting hormone (MIH) and
      ecdysone. MIH inhibits the synthesis of ecdysone in the Y-organ, resulting in
      molt suppression; it is a neuropeptide member belonging to the eyestalk
      CHH/MIH/GIH family. The cloning of MIH (formerly MIH-like) of the shrimp
      Metapenaeus ensis has been reported in a previous study. To obtain a large
      quantity of fusion protein for antibody production and biological assay, the cDNA
      encoding the shrimp MIH was inserted into the pRSET bacterial expression vector.
      His-tagged fusion protein was produced and purified by an Ni2+-charged affinity
      column. Polyclonal antibody to rMIH was subsequently obtained by immunizing
      rabbits with purified recombinant proteins. Results from Western blot analysis
      indicated that the antibody was specific. Furthermore, results from
      immunocytochemical analysis showed that specific cells in three different
      clusters of the X-organ, the sinus gland and the axonal tract of the eyestalk
      contain MIH. To test for the molt-inhibiting activity of rMIH, shrimp at
      intermolt stage were injected with rMIH and the molt cycle duration of the
      injected shrimp was monitored. A significant increase in molt cycle duration was
      recorded for the shrimp injected with the recombinant protein.

PMID- 11236001
TI  - Immunocytochemical demonstration of visual pigments in the degenerate retinal and
      pineal photoreceptors of the blind cave salamander (Proteus anguinus).
AB  - Visual pigments in the regressed eye and pineal of the depigmented neotenic
      urodele, the blind cave salamander (Proteus anguinus anguinus), were studied by
      immunocytochemistry with anti-opsin antibodies. The study included light- and
      electron-microscopic investigations of both the eye and the pineal organ. A
      comparison was made with the black pigmented subspecies Proteus anguinus parkelj
      (black proteus), which has a normal eye structure. In the retina of the black
      proteus, we found principal rods, red-sensitive cones and a third photoreceptor
      type, which might represent a blue- or UV-sensitive cone. Photoreceptors in the
      regressed eye of the blind cave salamanders from the Planina cave contained
      degenerate outer segments, consisting of a few whorled discs and irregular clumps
      of membranes. The great majority of these outer segments showed immunolabelling
      for the red-sensitive cone opsin and only a few of them were found to be positive
      for rhodopsin. An even more pronounced degeneration was observed in the
      photoreceptors of the animals derived from the Otovec doline, which are
      completely devoid of an outer segment, most of them not even possessing an inner
      segment. Even in some of these highly degenerate cells, the presence of rhodopsin
      could be detected in the plasma membrane; however, immunoreactions with
      antibodies recognizing cone visual pigment were negative. In the pineals of all
      studied animals, the degenerate photoreceptor outer segments were recognized
      exclusively by the antibody against the red-sensitive cone opsin. The presence of
      immunopositive visual pigments indicates the possibility of a retained light
      sensitivity in the blind cave salamander photoreceptors.

PMID- 11236002
TI  - Topology of the signal transduction of the G protein-coupled somatostatin
      receptor sst2 in human glioma cells.
AB  - By a dual approach, using electron microscopy and biochemical techniques, we
      investigated the topology of the somatostatin receptor sst2 with its inhibitory G
      protein Gialpha after ligand-induced stimulation and internalization in human
      glioma cells. On intact cells, the sst2 was labeled at 8 degrees C by an antibody
      directed to its extracellular sequence followed by a 15-nm gold-labeled secondary
      antibody. In the presence of the ligand, internalization was induced by exposure
      to 37 degrees C for 5-10 min. Then, cells were either fixed for immunoelectron
      microscopic analysis or homogenized for density gradient separation. After post
      embedding staining of the sst2-labeled sections with anti-Gialpha1- 3 or anti
      caveolin, a co-localization of sst2, Gialpha and caveolin was detected in
      endosomal vesicles after 5 min of internalization, but not after 10 min.
      Furthermore, the gold-labeled organelles containing the internalised receptor
      were separated from the non-labeled ones on sucrose gradients (density shift
      separation) and analyzed by Western blotting. Also here, in fractions with higher
      densities, sst2 could be costained with Gialpha and caveolin after 5 min. From
      these congruent results from both methods, it can be concluded that, in human
      glioma cells, the receptor sst2 (1) is internalised in caveolin-positive vesicles
      and (2) is neighboured to its Gialpha proteins at the plasma membrane and early
      endosomes.

PMID- 11236003
TI  - Distinctive spatiotemporal expression patterns for neurotrophins develop in
      gustatory papillae and lingual tissues in embryonic tongue organ cultures.
AB  - Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) mRNAs are
      expressed in the developing rat tongue and taste organs in specific
      spatiotemporal patterns. BDNF mRNA is present in the early lingual gustatory
      papilla epithelium, from which taste buds eventually arise, prior to the arrival
      of gustatory nerve fibers at the epithelium, whereas NT-3 initially distributes
      in the mesenchyme. However, a direct test for neural dependence of neurotrophin
      expression on the presence of innervation in tongue has not been made, nor is it
      known whether the patterns of neurotrophin expression can be replicated in an in
      vitro system. Therefore, we used a tongue organ culture model that supports taste
      papilla formation while eliminating the influence from sensory nerve fibers, to
      study neurotrophin mRNAs in lingual tissues. Rat tongue cultures were begun at
      embryonic day 13 or 14 (E13, E14), and BDNF, NT-3, nerve growth factor (NGF) and
      neurotrophin-4 (NT-4) mRNAs were studied at 0, 2, 3 and 6 days in culture. BDNF
      transcripts were localized in the gustatory epithelium of both developing
      fungiform and circumvallate papillae after 2 or 3 days in culture, and NT-3
      transcripts were in the subepithelial mesenchyme. The neurotrophin distributions
      were comparable to those in vivo at E13-E16. In 6-day tongue cultures, however,
      BDNF transcripts in anterior tongue were not restricted to fungiform papillae but
      were more widespread in the lingual epithelium, while the circumvallate trench
      epithelium exhibited restricted BDNF labeling. The NT-3 expression pattern
      shifted in 6-day organ cultures in a manner comparable to that in the embryo in
      vivo, and was expressed in the lingual epithelium as well as mesenchyme. NGF mRNA
      expression was subepithelial throughout 6 days in cultures. NT-4 mRNA was not
      detected. The neurotrophin mRNA distributions demonstrate that temporospatial
      localization of neurotrophins observed during development in vivo is retained in
      the embryonic tongue organ culture system. Furthermore, initial neurotrophin
      expression in the developing lingual epithelium, mesenchyme, and/or taste
      papillae is not dependent on intact sensory innervation. We suggest that patterns
      of lingual neurotrophin mRNA expression are controlled by the influence of local
      tissue interactions within the tongue at early developmental stages. However, the
      eventual loss of restricted BDNF mRNA localization from fungiform papillae in
      anterior tongue suggests that sensory innervation may be important for
      restricting the localized expression of neurotrophins at later developmental
      stages, and for maintaining the unique phenotypes of gustatory papillae.

PMID- 11236004
TI  - Distribution of B/K protein in rat brain.
AB  - B/K protein is a recently isolated member of the double C2-like-domain protein
      family, which is highly abundant in rat brain. We generated high-titer rabbit
      polyclonal antibodies with specificity to the 55-kDa rat B/K protein, and
      examined the expression pattern of B/K protein in rat brain using an
      immunohistochemical staining method. Immunoreactivity to B/K protein was widely
      found in distinct regions of rat brain: strongly in the hypothalamus, most of the
      circumventricular organs, the locus coeruleus, the A5 neurons of the pons, and
      the anterior pituitary; moderately in the anterior olfactory nucleus, the raphe
      nucleus, the subfornical organ, and the median eminence; and faintly in the
      olfactory bulb, the telencephalon, the substantia nigra pars compacta, and the
      ventral tegmental area. In contrast, immunoreactivity to B/K protein was not
      observed in the thalamus, the cerebellum, the posterior pituitary, or the spinal
      cord. In most of the B/K-expressing neurons, immunoreactivity was expressed
      mainly in soma but not in nerve fibers. B/K was also expressed in nonneuronal
      cells such as the tanycytes and the subcommissural organ. In the vasopressin
      secreting supraoptic and paraventricular nuclei of the hypothalamus, the site
      where B/K cDNA was originally isolated from, all of the neurons showing
      vasopressin immunoreactivity also expressed B/K protein, suggesting an overlap of
      their expression patterns.

PMID- 11236005
TI  - Occurrence and distribution of atrial natriuretic peptide-containing cells in the
      left ventricle of hypertensive rats. Effect of antihypertensive treatment.
AB  - In the ventricles of adult mammalian hearts, production of atrial natriuretic
      peptide (ANP) is negligible, restricted to the impulse-conducting cells, the
      papillary muscles, and a minority of subendocardial myocytes. ANP expression is
      reinduced in the ventricles of pressure-overloaded and failing hearts and is
      frequently used as a marker for myocyte hypertrophy. Using an immunohistochemical
      approach, we have characterized the size distribution of ANP-containing myocytes
      in the left ventricle of the spontaneously hypertensive rat (SHR) before and
      after chronic antihypertensive therapy and compared the results to age-matched
      normotensive Wistar rats (WR). Our findings show that in SHR the frequency of
      cells presenting ANP granularity is positively correlated with myocyte size
      (r=0.746, P<0.02). The highest proportion of ANP-positive myocytes (55-57%) was
      measured among cells of diameters 30-34 microm. In any corresponding cell size,
      the proportion of ANP-presenting myocytes was five- to tenfold higher in SHR than
      in the normotensive WR. We studied the effects of the antihypertensive drugs
      captopril, hydralazine, and nifedipine and found that, regardless of their effect
      on blood pressure or hypertrophy, all three eliminated ANP immunoproducts from
      the majority of the left ventricular myocytes and reduced the level of ANP mRNA,
      captopril being the most effective. The positive correlation between myocyte size
      and ANP expression was not maintained in the hearts of drug-treated SHR. Myocytes
      on the border of fibrotic areas or in regions of ANP presentation within the
      normal heart resisted the suppressive effect of the antihypertensive therapy,
      indicating that blood pressure or hypertrophy are not the sole correlates for ANP
      expression.

PMID- 11236006
TI  - Differential expression of integrin mRNAs and proteins during normal rat mammary
      gland development and in carcinogenesis.
AB  - A rat model was used to address the roles of integrins in the regulation of
      normal mammary epithelial cell (MEC) growth and differentiation and in mammary
      carcinogenesis. The expression of integrins alpha5, alpha6, beta1, and beta4 was
      examined via Northern and Western blotting analyses in freshly isolated MEC from
      various postnatal developmental stages. mRNAs for all four integrins were
      detectable at puberty and were increased during pregnancy. During lactation, the
      expression of alpha5, alpha6, and beta1 integrin mRNAs reached a peak, whereas
      that of beta4 integrin decreased dramatically. At day 7 of involution, the levels
      of all four integrin mRNAs were similar to or slightly higher than that of the
      pubertal mammary gland. Although alpha5 integrin protein decreased during
      pregnancy and lactation, beta1 and beta4 integrin proteins had similar profiles
      as the expression of their respective mRNAs, suggesting that integrin gene
      expression is regulated at both transcriptional and post-transcriptional levels.
      All four integrins were heterogeneously expressed in 7,12
      dimethylbenz[a]anthracene- and N-nitroso-N-methyl-urea-induced mammary tumors and
      in RBA and NMU rat mammary tumor cell lines. Adhesion assays showed that isolated
      MEC interacted with fibronectin to a greater extent than with laminin and
      collagen I in vitro, and that tumor cells with altered integrin expression
      exhibited greater adhesive ability to various substrata. Together, our results
      indicate that alpha5, alpha6, beta1, and beta4 integrins are differentially
      expressed during normal MEC development and in mammary tumors, supporting the
      hypothesis that these integrins play important yet complex roles in the mammary
      gland.

PMID- 11236007
TI  - Upregulation of the p75 low-affinity neurotrophin receptor by phagocytically
      active perivascular active cells in the rat neural lobe.
AB  - Expression of the p75 low-affinity neurotrophin receptor (p75NTR) was
      investigated immunocytochemically at the light and ultrastructural level during
      the axonal degeneration that follows partial denervation of the rat neural lobe
      (NL) and following systemic administration of lipopolysaccharide (LPS). A
      significant increase in the intensity and extent of p75NTR immunoreactivity in
      the NL of partially denervated animals compared with age-matched, sham-operated
      controls was observed at 5-10 days postdenervation, with immunoreactivity
      returning to control values by 35 days. Dual-label confocal comparison of p75NTR
      localization with that of the C3bi complement receptor, a microglial marker, and
      S100, an astrocyte-specific Ca2+-binding protein, revealed no colocalization.
      Immunoelectron-microscopic examination demonstrated that the p75NTR
      immunoreactivity is present in a subpopulation of cells located within the
      extensive perivascular space of the NL. No examples of p75NTR-immunoreactive
      pituicytes or endothelia were observed at the light or ultrastructural level.
      Dense p75NTR immunoreactivity was frequently observed surrounding endocytotic
      omega profiles of plasmalemma engulfing extracellular debris as well as lining
      vacuoles within the cytoplasm of perivascular cells. The association of p75NTR
      with phagocytosis was confirmed by confocal microscopy, showing the presence of
      p75NTR in all cells expressing the ED-1 antigen, which is restricted to the
      lysosomal membrane of phagocytes (Damoiseaux et al. 1994). Likewise, a marked
      increase in p75NTR and ED-1 immunoreactivity was observed in the NL following
      systemic administration of LPS. These results suggest a strong correlation
      between modulation of p75NTR immunoreactivity and conditions that induce high
      levels of phagocytic activity by perivascular cells in the NL of the rat.
      Implications for understanding the mechanisms by which phagocytes may support
      compensatory responses to neuronal injury are discussed.

PMID- 11236008
TI  - Putative role of basement membrane for dentinogenesis in the mesenchyme of murine
      dental papillae in vitro.
AB  - In a new culture-conditioning system of agar-coated mesenchyme of isolated
      incisor dental papillae, dentinogenesis has been induced adjacent to an agar
      substratum that functions as a foothold for cell immobilisation. To elucidate the
      role of the basement membrane (BM) in dentinogenesis, we have examined the way in
      which dentinogenesis depends upon BM components or transforming growth factor
      (TGF)-beta1 in this system. At the mesenchymal-epithelial junction of odontogenic
      organs (cut incisor tooth germs), TGF-beta1 visibly increased in the BM during
      incubation. In isolated dental papillae, BM components were synthesised and
      deposited at aligned peripheral cells of the explants, together with an
      increasing amount of TGF-beta1. These components were not assembled into
      extracellular matrix (ECM)-absorbed agar adjacent to explants, although
      dentinogenesis proceeded in the presence of pericellular BM components associated
      with TGF-beta1. When signalling via TGF-beta type II receptors was blocked,
      neither ECM production nor dentinogenesis was observed but explants partially
      detached from the agar surface, presumably as a result of the suppressed
      production of ECM, since attachment was retained by pre-coating explants with
      artificial matrices. Rescue experiments showed that TGF-beta1 regulated
      dentinogenesis through ECM production. With regard to BM components, inducible
      dentinogenesis was Arg-Gly-Asp (RGD)-dependent. Thus, pericellular BM components
      associated with TGF-beta1 and an ECM-absorbed agar substratum, which affects
      dentinogenesis, synergistically play a role similar to that of BM components in
      vivo. The BM therefore serves as a structural meshwork that acts as a foothold
      for cell immobilisation; its components act as ligands for RGD-dependent cell
      adhesion and it stores TGF-beta1, which regulates ECM production.

PMID- 11236009
TI  - Public health in the new millennium III: global health and the economy.

PMID- 11236010
TI  - Soft drinks in schools.

PMID- 11236011
TI  - Bioterrorism "preparedness": dual use or poor excuse?

PMID- 11236012
TI  - Gun-related violence.

PMID- 11236013
TI  - The case against the gun industry.

PMID- 11236014
TI  - Charity care programs: part of the solution or part of the problem?

PMID- 11236015
TI  - Tattoos: a photo essay.

PMID- 11236016
TI  - Use of passive surveillance data to study temporal and spatial variation in the
      incidence of giardiasis and cryptosporidiosis.
AB  - OBJECTIVE: The goal of this study was to evaluate temporal and spatial variations
      in the reporting of cases of giardiasis and cryptosporidiosis to a passive
      surveillance system, and to assess the relationship of those variations to source
      of drinking water, adjusting for socioeconomic variables. METHODS: The authors
      analyzed temporal and spatial patterns for 4,058 cases of giardiasis and 230
      cases of cryptosporidiosis reported to the Massachusetts Department of Public
      Health for 1993-1996. They linked each reported case to a database containing
      information on source of residential water supply and socioeconomic
      characteristics and evaluated the association between these factors and reporting
      rates using regression techniques. RESULTS: Reports of giardiasis and
      cryptosporidiosis were highest for the mixed unfiltered drinking water supply
      category. Reports of giardiasis were associated with income levels. Increases in
      reporting for both giardiasis and cryptosporidiosis were seen in summer to early
      fall. During a suspected outbreak of cryptosporidiosis n the city of Worcester in
      1995, a significant increase in reported cases was also observed in the Boston
      metropolitan area. Following the suspected outbreak, weekly giardiasis rates
      increased slightly in Worcester and the Boston metropolitan area, while reporting
      of cryptosporidiosis increased dramatically. CONCLUSIONS: Consistently collected
      passive surveillance data have the potential to provide valuable information on
      the temporal variation of disease incidence as well as geographic factors.
      However, passive surveillance data, particularly in the initial period of
      surveillance, may be highly sensitive to patterns of diagnosis and reporting and
      should be interpreted with caution.

PMID- 11236017
TI  - Increasing access to dental care for medicaid preschool children: the Access to
      Baby and Child Dentistry (ABCD) program.
AB  - OBJECTIVE: Washington State's Access to Baby and Child Dent stry (ABCD) Program,
      first implemented in Spokane County in 1995, offers extended dental benefits to
      participating Medicaid-enrolled children and higher fees for certified providers.
      This study aimed to determine the program's effect on children's dental
      utilization and dental fear, and on parent satisfaction and knowledge. METHODS:
      The study used a posttest-only comparison group design. Trained interviewers
      conducted telephone interviews with 465 parents of chi dren ages 13 to 36 months
      (49% ABCD, 51% Medicaid-enrolled children not in ABCD). One year later, 282 of
      465 parents completed a follow-up survey. Utilization and expenditures were
      calculated from Medicaid claims. RESULTS: Forty-three percent of children in the
      ABCD Program visited a dentist in the follow-up year, compared with 12% of
      Medicaid-enrolled children not in the ABCD Program. An ABCD child was 5.3 times
      as likely to have had at least one dental visit as a child not in the program.
      ABCD children were 4 to 13 times as likely to have used specific dental services.
      Parents of ABCD children were more likely to report having ever tried to make a
      dental appointment, less likely to report that their children were fearful of the
      dentist, and were more satisfied, compared to parents of non-ABCD children.
      CONCLUSION: The authors conclude that the ABCD Program was effective in
      increasing access for preschool children enrolled in Medicaid, reducing dental
      fear, and increasing parent satisfaction.

PMID- 11236018
TI  - Acceptance of HIV testing during prenatal care. Perinatal Guidelines Evaluation
      Project.
AB  - OBJECTIVE: The purpose of this study was to assess the factors associated with
      acceptance of HIV testing during pregnancy on the part of women receiving
      prenatal care at public clinics. METHODS: Trained interviewers recruited and
      interviewed 1,357 women receiving prenatal care at clinics in Florida,
      Connecticut, and New York City. RESULTS: Eighty-six percent of participants
      reported having been tested or having signed a consent form to be tested.
      Acceptance of testing was found to be related to strong beliefs about the
      benefits of testing, knowledge about vertical transmission, perceived provider
      endorsement of testing, and social support. Women who declined testing said they
      did so because they did not perceive themselves to be at risk for HIV (21%) or
      they faced administrative difficulties (16%) with some aspect of the testing
      process (for example, scheduling, limited availability of pre-test counselors).
      CONCLUSIONS: Acceptance rates can be increased when women understand the modes of
      vertical transmission and the role of medication regimens in preventing
      transmission; believe that prenatal identification of HIV can promote the health
      of mother and child; and perceive their providers as strongly endorsing testing.
      These points can be woven into a brief pre-test counseling message and made a
      routine component of prenatal care.

PMID- 11236019
TI  - Incidence of Rocky Mountain spotted fever among American Indians in Oklahoma.
AB  - OBJECTIVE: Although the state of Oklahoma has traditionally reported very high
      incidence rates of Rocky Mountain spotted fever (RMSF) cases, the incidence of
      RMSF among the American Indian population of the state has not been studied. The
      authors used data from several sources to estimate the incidence of RMSF among
      American Indians in Oklahoma. METHODS: The authors retrospectively reviewed an
      Indian Health Service (IHS) hospital discharge database for 1980-1996 and
      available medical charts from four IHS hospitals. The authors also reviewed RMSF
      case report forms submitted to the Centers for Disease Control and Prevention
      (CDC) for 1981-1996. RESULTS: The study data show that American Indians in the
      IHS Oklahoma City Area were hospitalized with RMSF at an annual rate of 48.2 per
      million population, compared with an estimated hospitalization rate of 16.9 per
      million Oklahoma residents. The majority of cases in the IHS database (69%) were
      diagnosed based on clinical suspicion rather than laboratory confirmation. The
      incidence of RMSF for Oklahoma American Indians as reported to the CDC was 37.4
      cases per million, compared with 21.6 per million for all Oklahoma residents (RR
      1.7, 95% confidence interval [CI] 1.5, 2.1). CONCLUSIONS: Rates derived from the
      IHS database may not be comparable to state and national rates because of
      differences in case inclusion criteria. However, an analysis of case report forms
      indicates that American Indians n Oklahoma have a significantly higher incidence
      of RMSF than that of the overall Oklahoma population. Oklahoma American Indians
      may benefit from educationa campaigns emphasizing prevention of tick bites and
      exposure to tick habitats.

PMID- 11236020
TI  - Addressing drug abuse: policy deliberations in the great south land.

PMID- 11236021
TI  - Surgeon General's report on oral health.

PMID- 11236022
TI  - Biological modifiers as potential radiosensitizers: targeting the epidermal
      growth factor receptor family.
AB  - The epidermal growth factor receptor family plays an important role in the
      pathogenesis of human epithelial tumors. Overexpression is associated with poor
      prognosis and resistance to therapy. Epidermal growth factor receptor family
      members activate signal transduction pathways that have been implicated in
      radioresistance, and inhibition of signal transduction pathways involved in
      epidermal growth factor receptor family member signaling causes
      radiosensitization. Recent encouraging results indicate that epidermal growth
      factor receptor family member inhibitors may be specific, effective
      radiosensitizers in tumors that overexpress one or more of these receptors.

PMID- 11236023
TI  - Trastuzumab and chemotherapeutics: drug interactions and synergies.
AB  - Previous studies have shown a synergistic interaction between trastuzumab
      (Herceptin; Genentech, Inc, South San Francisco, CA) and the cytotoxic drug
      cisplatin in human breast cancer cells. To define the nature of the interaction
      between trastuzumab and other classes of cytotoxic drugs, we applied multiple
      drug effect/combination index isobologram analysis to a variety of
      chemotherapeutic drug/trastuzumab combinations in vitro. Synergistic interactions
      at clinically relevant drug concentrations were observed for trastuzumab in
      combination with cisplatin, docetaxel, thiotepa, 4-OH cyclophosphamide,
      vinorelbine, and etoposide. Additive cytotoxic effects were observed with
      trastuzumab plus doxorubicin, paclitaxel, methotrexate, and vinblastine. One
      drug, 5-fluorouracil was found to be antagonistic with trastuzumab in vitro. In
      vivo drug/trastuzumab studies were conducted with HER-2/neu-transfected MCF7
      human breast cancer xenografts in athymic mice. Combinations of trastuzumab plus
      cisplatin, docetaxel, cyclophosphamide, doxorubicin, paclitaxel, methotrexate,
      etoposide, and vinblastine in vivo resulted in a significant reduction in
      xenograft volume compared to chemotherapy-alone controls (P < .05). The
      synergistic interaction of trastuzumab with specific chemotherapeutic agents
      suggests rational combinations for testing in human clinical trials.

PMID- 11236024
TI  - Ongoing and planned adjuvant trials with trastuzumab.
AB  - HER-2 (c-erbB-2, neu) is an important prognostic and predictive factor in breast
      cancer. Clinical trials utilizing a humanized version of the anti-HER-2 murine
      monoclonal antibody 4DS, trastuzumab (Herceptin; Genentech Inc, South San
      Francisco, CA), have shown antitumor activity in patients with HER-2-positive
      metastatic breast cancer. Improved response and survival rates have been shown
      when trastuzumab was added to first-line combination chemotherapy with
      anthracycline/cyclophosphamide or paclitaxel, compared to the same chemotherapy
      alone. The Breast Cancer Intergroup has recently completed several trials
      evaluating new chemotherapy treatment approaches for patients with node-positive
      breast cancer, which form the basis for several ongoing and planned clinical
      trials incorporating trastuzumab. These clinical trials and the evolving role of
      trastuzumab-containing adjuvant systemic therapy for breast cancer will be
      reviewed.

PMID- 11236025
TI  - HER-2/neu (erbB-2) and the cell cycle.
AB  - Signaling by the HER-2 proto-oncogene product results in the activation of
      several biochemical pathways, which in turn modulate the expression and function
      of cell cycle regulators. These alterations of cell cycle regulatory molecules
      may be critical for the conception and maintenance of the transformed phenotype
      conferred by HER-2 gene amplification and overexpression. On the other hand,
      blockade of HER-2 function with a therapeutic intent will require the reversal of
      these effects on cell cycle regulatory molecules in order for these interventions
      to be effective. Data is presented to suggest that the G1 cyclin D1 and the
      cyclin-dependent kinase inhibitor p27KIP1 may be involved in subversion of the
      G1/S traverse by signaling pathways activated by HER-2 function.

PMID- 11236026
TI  - Ongoing and planned trials of hormonal therapy and trastuzumab.
AB  - Studies with human breast cancer cell lines have shown a causal association
      between overexpression of the HER-2/neu proto-oncogene receptor and the
      acquisition of resistance to tamoxifen. Some clinical studies also indicate that
      patients with tumors showing high HER-2 levels or high levels of the circulating
      ectodomain of HER-2 may have a lower response to tamoxifen compared with tumors
      with low HER-2 levels or low circulating ectodomain. Treatment with anti-HER-2
      antibodies seems to restore tamoxifen activity in some experimental systems.
      However, whether anti-HER-2 therapies will increase tamoxifen action and/or
      reverse this putative oncogene-mediated resistance in patients with estrogen
      receptor-positive, hormone-dependent tumors, is unclear. We are conducting a
      phase II trial of a humanized anti-HER-2 monoclonal antibody, trastuzumab
      (Herceptin; Genentech, Inc, South San Francisco, CA) in combination with
      tamoxifen in patients with estrogen receptor-positive metastatic breast cancer.
      Other prospective randomized clinical trials are needed to directly evaluate the
      contribution of HER-2 signaling to antiestrogen resistance in vivo.

PMID- 11236028
TI  - The role of HER-2 expression in predicting response to therapy in breast cancer.
AB  - HER-2 expression may have predictive value regarding response to therapeutic
      interventions in breast cancer. A number of reports describe the interaction of
      HER-2 overexpression and tamoxifen, but data are inconclusive. Chemotherapy
      trials have supported an interaction between HER-2 overexpression and
      chemotherapy sensitivity (cyclophosphamide/methotrexate/5-fluorouracil resistance
      and doxorubicin sensitivity) which is compelling. More recently, HER-2 has been
      the target for Food and Drug Administration-approved antibody therapy,
      trastuzumab (Herceptin; Genentech, Inc, South San Francisco, CA). The Clinical
      Trials Assay, a scoring system for tumor material, has been used successfully in
      the trastuzumab clinical development program. As many of the early studies
      evaluating the role of HER-2 were retrospective, controlled prospective studies
      are needed to best determine the value of trastuzumab in the adjuvant clinical
      setting.

PMID- 11236027
TI  - Trastuzumab in combination with chemotherapy for the treatment of metastatic
      breast cancer.
AB  - Metastatic breast carcinoma still remains an incurable condition. The relentless
      search for novel agents that might prove useful for management has evolved toward
      monoclonal antibodies, in part because of a rapidly expanding understanding of
      breast cancer biology. Trastuzumab (Herceptin; Genentech, Inc, South San
      Francisco, CA) is a recombinant humanized monoclonal antibody against the HER-2
      receptor that has shown antitumor activity as a single agent in phase I and II
      trials of patients with metastatic breast cancer overexpressing HER-2. The
      observation of increased antitumor activity between trastuzumab and some
      chemotherapeutic agents in preclinical models has prompted its use in combination
      with several drugs. Of particular interest is the use of trastuzumab with
      paclitaxel. Two trials were presented at the 1999 meeting of the American Society
      of Clinical Oncology that evaluated this combination. One multicenter phase III
      trial showed clinical benefit and increased survival for patients with HER-2
      overexpressing metastatic breast cancer treated with chemotherapy plus
      trastuzumab. A phase II trial, reviewed in this report, evaluated the efficacy
      and safety of weekly paclitaxel plus trastuzumab for patients with metastatic
      breast carcinoma, including those overexpressing and nonoverexpressing HER-2.

PMID- 11236030
TI  - Monoclonal antibody treatment of solid tumors: a coming of age.
AB  - Over the past 5 years there has been a renewed interest in the use of monoclonal
      antibodies and immunoconjugates in the treatment of nonhematologic malignancies.
      This enthusiasm has stemmed from advances in recombinant technology allowing for
      the production of chimeric and humanized antibodies, from Food and Drug
      Administration approval of radioimmunoconjugates for use in diagnosis and staging
      in colorectal, ovarian, and prostate cancer, from studies demonstrating durable
      response rates in lymphoma and breast cancer, and from trials demonstrating
      marked efficacy of radiolabeled antibodies in the treatment of non-Hodgkin's
      lymphoma. Part of the success of chimeric and humanized antibodies in treating
      solid tumors relates to the lack of human antimouse antibody formation along with
      enhanced immunogenic effector mechanisms. The pitfalls underlying early trials of
      murine monoclonal antibodies in solid tumors and newer antibody approaches using
      unique antigen targets, bifunctional constructs, and alternative routes of
      antibody administration will be discussed.

PMID- 11236029
TI  - HER-2/neu as a therapeutic target in non-small cell lung cancer, prostate cancer,
      and ovarian cancer.
AB  - HER-2/neu is overexpressed in most epithelial malignancies. Lung cancer, prostate
      cancer, and ovarian cancer are common epithelial tumors in which clinical trials
      are currently in progress to explore the potential therapeutic role for
      monoclonal antibodies to HER-2/neu (trastuzumab [Herceptin; Genentech, Inc, South
      San Francisco, CA]). In preclinical studies with tumor cell lines, trastuzumab
      was found to have additive and synergistic effects with some chemotherapeutic
      agents. Clinical trials investigating combination chemotherapy with trastuzumab
      and a variety of chemotherapeutic agents are already in progress in lung cancer.

PMID- 11236031
TI  - Clinical trials of HER-2/neu-specific vaccines.
AB  - Recently there has been a renewed interest in developing vaccines for use in
      cancer treatment. Part of this interest stems from a better understanding of the
      immune system, the identification of a number of T-cell-specific tumor antigens,
      more effective adjuvants, and the ability to construct more immunogenic molecules
      using recombinant DNA techniques. Studies from several laboratories have shown
      that breast cancer patients have preexisting immunity to the HER-2/neu
      oncoprotein receptor (HER-2) in the form of elevated antibody titers and T-cell
      immunity. Preclinical studies showed enhanced delayed-type hypersensitivity and
      cytotoxic T-lymphocyte precursors in spleens from animals immunized with several
      human leukocyte antigen class I and class II peptides derived from the HER-2
      protein. Phase I trials of these peptides combined with the cytokine granulocyte
      macrophage colony-stimulating factor as a part of therapy in patients with HER-2
      positive cancers have shown minimal local toxicity, along with enhanced helper T
      cell activity and antibody production in patients with minimal disease. Increases
      in cytotoxic T-lymphocyte precursor activity were less frequent, but in some
      cases could be enhanced when patient lymphocytes were incubated ex vivo with the
      proinflammatory cytokine interleukin-12. Other preclinical studies designed to
      enhance HER-2 peptide immunogenicity are in progress. Additional current and
      future clinical trials using HER-2-derived vaccines will be discussed.

PMID- 11236032
TI  - A potential role for activated HER-2 in prostate cancer.
AB  - The epidermal growth factor (also known as HER or ErbB) family of receptor
      tyrosine kinases are important mediators of cell growth, differentiation, and
      survival. At present there are 10 ligands that bind directly to epidermal growth
      factor, HER-3, or HER-4. Although none of these ligands bind directly to HER-2,
      it is recruited to these receptor complexes and also becomes activated. A
      monoclonal antibody directed against HER-2, 2C4, inhibits the association of HER
      2 with other HER family members. Ligand-activated HER-2 may also play a role in
      cancers, particularly those that do not overexpress HER-2 at high levels. For
      example, when prostate cancers progress from an androgen-dependent to an androgen
      independent phenotype, epidermal growth factor pathways are frequently activated.
      2C4 will inhibit the growth of both androgen-dependent and androgen-independent
      prostate tumors grown as xenografts in athymic mice.

PMID- 11236033
TI  - New insights into anti-HER-2 receptor monoclonal antibody research.
AB  - Abnormalities in the expression, structure, or activity of proto-oncogene
      products contribute to the development and maintenance of the malignant
      phenotype. For example, c-erbB-2 encodes the HER-2 receptor (also known as c-erbB
      2 or c-neu) that is overexpressed, amplified, or both in a number of human
      malignancies including breast, ovarian, colon, lung, prostate, and cervical
      cancers. In addition to deregulation of cell-surface HER receptors, cancer cells
      often show excessive activation and/or nonattenuation of growth factor--inducible
      signaling components, as well as their downstream transcription factors. Current
      approaches to target HER-2 pathways include downregulation of HER-2 by the
      adenovirus 5E1A, antisense phosphothionate oligonucleotides, ribozyme, and
      targeting tyrosine kinase using specific inhibitors. Because growth factors
      regulate the proliferation of cancer cells by activating receptors on the surface
      of cells, one obvious approach to control cell proliferation is to interfere with
      the growth factor receptor-mediated autocrine/ paracrine growth stimulation by
      antireceptor-blocking monoclonal antibodies. Therefore, a large number of
      scientists are attempting to control the growth of cancer cells using agents that
      inhibit one or more of the above steps of growth factor action. Recently
      completed clinical trials established the usefulness of a humanized form of 4DS
      monoclonal antibody, trastuzumab (Herceptin; Genentech, Inc, South San Francisco,
      CA), against some forms of breast tumors overexpressing HER-2 receptors. Using in
      vitro models, recent studies have shown that HER-2 overexpression may not be a
      prerequisite for invasion of breast cancer cells, as HER-2 activation by
      heregulin, which binds to HER-3 or HER-4 and transphosphorylates HER in
      noninvasive breast cancer cells, could lead to increased motility, enhanced
      gelatinolytic activity, and invasion. Furthermore, these ligand-driven phenotypic
      changes were completely suppressed by trastuzumab, which also blocked
      interactions between HER-2 and HER-3 receptors in heregulin-treated breast cancer
      cells, and inhibited the phosphatidylinositol-3' kinase-dependent pathway, but
      not the mitogen-activated protein kinase pathway. These phenotypic effects of
      anti-HER-2 monoclonal antibody are of special interest, because they point to
      potential therapeutic effects of trastuzumab in inhibiting the invasion and
      metastasis of breast cancer with low receptor expression.

PMID- 11236034
TI  - Myocyte survival pathways and cardiomyopathy: implications for trastuzumab
      cardiotoxicity.
AB  - Recent clinical studies have documented the efficacy of trastuzumab (Herceptin;
      Genentech, Inc, South San Francisco, CA) as a new biologically targeted therapy
      for erbB-2 receptor-positive forms of breast cancer. During the course of a large
      scale clinical trial, a subset of patients reported the onset of symptoms and
      signs of cardiac failure that appeared to be aggravated by concomitant exposure
      to anthracyclines. The mechanisms responsible for this cardiac toxicity are
      unclear. However, new insights into the pathways that lead to other forms of
      heart failure have identified a pivotal role for myocyte survival pathways in
      preventing the onset of cardiomyopathy and associated heart failure in
      genetically engineered animal models of the disease. This mini-review highlights
      these recent findings and suggests the possibility that the loss of erbB-2
      receptor-dependent myocyte survival pathways may create a susceptibility for the
      onset of heart failure in response to the cardiotoxicity of anthracycline
      treatment. The possibility exists that the divergent susceptibility for the onset
      of cardiotoxicity among patients who have received trastuzumab might ultimately
      reflect an inherent genetic susceptibility to the diverse mechanisms that
      initiate, promote, and suppress the complex pathways to heart failure.

PMID- 11236035
TI  - Chronic lung disease: oxygen dogma revisited.
AB  - Since the discovery of retrolental fibroplasia, and the role of oxygen in its
      development, oxygen has been considered a double-edged sword in neonatal
      medicine, the utmost care being exercised in order not to give too much oxygen
      (1). However, the important observation that hypoxaemia might induce pulmonary
      vasoconstriction (2) and airway constriction (3) in infants at risk for
      bronchopulmonary dysplasia has resulted in only a minor upward adjustment of
      oxygen supplementation in many neonatal units. Since oxygen toxicity has long
      been linked not only to retinopathy of prematurity but also to bronchopulmonary
      dysplasia (4), it is relevant to ask whether an increased FiO2 might have any
      detrimental effects on babies.

PMID- 11236036
TI  - Postnatal steroids: a dilemma for the neonatologist.

PMID- 11236037
TI  - Aetiology and outcome of pneumonia in human immunodeficiency virus-infected
      children hospitalized in South Africa.
AB  - To determine the aetiology and outcome of pneumonia in human immunodeficiency
      virus (HIV)-infected children, we prospectively investigated 250 children
      hospitalized with pneumonia who were known or clinically suspected to be HIV
      positive, or who required intensive care support in Cape Town, South Africa.
      Blood culture, induced sputum or bronchoalveolar lavage, nasopharyngeal aspirate
      and gastric lavage were performed. Of the total, 151 children (60.4%) were HIV
      infected. Pneumocystis carinii pneumonia (PCP), occurring in 19 (7.6%) children
      (15 HIV-positive), was the AIDS-defining infection in 20.3%. The incidence and
      type of bacteraemia (14.3%) were similar in HIV-positive and HIV-negative
      patients; S. pneumoniae (5%) and S. aureus (2%) were the predominant isolates.
      Sputum or BAL cultures yielded bacteria in 145 of 243 (60%) specimens; viruses
      were cultured in 37 (15.2%). Bacterial prevalence (including M. tuberculosis in
      8%) and anti-microbial resistance did not differ by HIV status except for S.
      aureus which was more common in HIV-infected children. Thirty-one (20%) HIV
      positive and 8 (8%) HIV-negative children died [RR 1.16 (95% CI 1.05-1.28),
      p=0.008]; using multiple logistic regression, PCP was the only risk factor for
      mortality (p = 0.03). CONCLUSION: In South Africa, PCP is an important AIDS
      defining infection in children; bacterial pathogens occur commonly and with a
      similar prevalence in HIV-positive and HIV-negative children hospitalized for
      pneumonia. HIV-infected children with pneumonia have a worse outcome than HIV
      negative patients.

PMID- 11236038
TI  - Chlamydia pneumoniae in children undergoing adenoidectomy.
AB  - Chlamydia pneumoniae is a common respiratory pathogen which is often found in
      paediatric populations. Little is known about the true colonization rate and the
      localization of the bacteria in the respiratory tract. In this study,
      immunohistochemistry was used to examine adenoids from 69 children undergoing
      elective adenoidectomy. Throat swabs for polymerase chain reaction (PCR) and
      blood samples for serology were also obtained. Chlamydia pneumoniae was
      demonstrated in the adenoids by immunohistochemistry in 68 of the children. Five
      children (7%) had a positive C. pneumoniae PCR test from throat swabs and 14
      children (20%) had detectable antibodies by the microimmunofluorescence
      technique. CONCLUSION: The results suggest that C. pneumoniae is a common finding
      in the adenoids of children undergoing adenoidectomy. Whether or not C.
      pneumoniae plays a pathogenic role in this patient population could not be
      determined from the data obtained in this investigation.

PMID- 11236039
TI  - Plasma thrombomodulin levels in children with atopic dermatitis.
AB  - Plasma thrombomodulin (TM) levels were measured in 68 patients with atopic
      dermatitis (AD) and 35 controls. Plasma TM levels in patients with AD were
      significantly higher than those of controls (p < 0.01). A significant correlation
      was observed between plasma TM levels and skin scores of AD or peripheral
      eosinophil counts (p < 0.01). There was also a positive correlation between
      plasma TM and vascular cell adhesion molecule-1 levels (p < 0.05). CONCLUSION:
      These results suggest that plasma TM levels may reflect a severity of AD and/or
      endothelial cell activation induced by an allergic inflammation.

PMID- 11236040
TI  - Comparison of handling and acceptability of two spacer devices in young children
      with asthma.
AB  - This study compared parents' preference for two spacer devices, NebuChamber and
      Babyhaler for the treatment of young children with asthma. In this open, cross
      over study 141 patients (aged 5-57 mo) who used inhaled steroids via a spacer
      device were randomized to budesonide via NebuChamber or beclomethasone
      dipropionate via Babyhaler. Both treatments were given by the parents twice daily
      for 2 wk. At the final visit parents completed a questionnaire on preference in
      general and for a given set of features. Acceptability and handling were scored
      in a diary. Diary scores on acceptability by the child and handling of both
      spacer devices were comparable. In the preference questionnaire, 68% of parents
      preferred NebuChamber [95% confidence interval (CI) 60-76] and 25% Babyhaler (95%
      CI 18-33). The preference was independent of the type of spacer used before the
      study and was also apparent in the different features: acceptability by child,
      carrying around, cleaning, close fitting of face mask, assembling and
      disassembling, damage resistance and size. These differences were statistically
      significant for all features, except for acceptability by the child. CONCLUSION:
      Two-thirds of parents prefer NebuChamber over Babyhaler for the treatment of
      their young asthmatic children.

PMID- 11236041
TI  - Short-term effects of severe hypoglycaemia in children and adolescents with type
      1 diabetes. A cost-of-illness study.
AB  - The aim of this study was to describe costs and other short-term effects of
      severe hypoglycaemia in children and adolescents with type 1 diabetes. The study
      comprised a geographic population of 129 patients <19 y of age with families
      prospectively registering detailed data after self-reported severe hypoglycaemia.
      In the period Jan.-Dec. 1998, 16 events were reported with unconsciousness and 95
      events without unconsciousness but needing the assistance of another person. Of
      all events, 20-30% had effects requiring the assistance of people other than
      parents, school absence, parents' absence from work, extra transport and/or
      telephone calls. Patient (family) activities were cancelled after 10% (5%) of
      events. Increased worry for parents was reported after 8% and poor sleep after 7%
      of events. Hospital visits took place at 5% and hospitalizations at 3% of all
      events. Patients with severe hypoglycaemia indicated lower global quality of life
      (p=0.0114). The average socio-economic burden for events of severe hypoglycaemia
      was estimated at EURO 17,400 yearly per 100 type 1 diabetes patients. Average
      cost was estimated at EURO 239 per event of severe hypoglycaemia with
      unconsciousness or EURO 478 yearly per patient with unconsciousness, and EURO 63
      per event of severe hypoglycaemia without unconsciousness but needing assistance
      from another person or EURO 307 yearly per patient in this category. These are
      conservative estimates and do not include unpaid time and other intangibles,
      possible road traffic accidents, disabling or premature deaths. CONCLUSIONS: The
      results suggest the potential for socio-economic savings and increased quality of
      life for patients and families from severe hypoglycaemia prevention programs.

PMID- 11236042
TI  - Generalization of back education principles by elementary school children:
      evaluation with a practical test and a candid camera observation.
AB  - The efficacy of back education in elementary school children was shown using a
      practical test. Similar results in a candid camera evaluation were questioned.
      The purposes of this study were (i) to explore the relationship between the
      results of a practical test and the results of a candid camera procedure when
      evaluating back education principles, and (ii) to investigate whether in a candid
      camera procedure scores are still better in pupils who followed a back education
      programme than in controls. A candid camera evaluation followed by a practical
      test was performed in 71 pupils who had participated in a back education
      programme and 60 controls. Correlations between the two evaluation methods were
      significant but weak for 5 of the 9 test items in the intervention group (Rs 0.26
      0.46) and for 7 test items in the control group (Rs 0.38-0.58). The difference in
      sum scores between the evaluation methods was significantly higher in the
      intervention group than in the control group (p < 0.001). The intervention group
      scored higher than the control group for 8 practical test items and 7 candid
      evaluation items. CONCLUSION: The study results question the use of a practical
      test for the individual evaluation of back education principles but show the
      usefulness of a practical test to study programme efficacy. As some principles
      seem to have become a habit, while for the implementation of others the pupils
      need external stimuli, the effects of more specific guidelines for parents and
      teachers to generalize back education principles require further study.

PMID- 11236043
TI  - Possible new autosomal recessive syndrome of congenital lymphoedema, nail
      dystrophy and esotropia in a Saudi family.
AB  - This paper presents a family case of two brothers and two sisters with congenital
      lower limb lymphoedema, nail dystrophy, and with esotropia in two of them. They
      are offspring of healthy parents who are first cousins. This combination of
      congenital lymphoedema, nail dystrophy and esotropia in this sibship differs from
      other reported cases of congenital lymphoedema and most likely constitutes a
      previously unrecognized autosomal recessive syndrome.

PMID- 11236044
TI  - Comparison of EMLA cream versus placebo in children receiving distraction therapy
      for venepuncture.
AB  - Eutectic mixture of local anaesthetics (EMLA) cream is used routinely as a local
      anaesthetic prior to venepuncture in children. Despite this, however, a
      significant proportion of children will still be distressed. Cognitive
      behavioural interventions, such as distraction by breathing and blowing
      exercises, have been used and found to be helpful as alternative coping
      strategies. There is, however, a paucity of data regarding effectiveness. We have
      evaluated the efficacy of distraction therapy as a coping strategy before and
      during venepuncture, and in these children evaluated the need for EMLA using a
      prospective, randomized, double-blind, placebo-controlled clinical trial. Twenty
      eight children attending for venepuncture were recruited, median age 6 y (range 4
      8 y), and randomly allocated to receive either EMLA or a placebo cream. All were
      given distraction therapy prior to and during the procedure by a play specialist.
      Venepuncture was carried out by one investigator. A modified paediatric pain
      assessment chart was used for objective pain score at the end of the procedure.
      After one exclusion, the treatment group (17 children) and the placebo group (10
      children) were similar: median age of 6 and 7 y (range 4-8), median baseline and
      post-procedure heart rate and oxygen saturation. The median (interquartile range)
      for total pain score in the treatment group was 1 (0 to 4.5) and in the control
      group 1 (0 to 2.3). There was no significant difference in pain score between the
      two groups (Mann-Whitney test, p = 0.7). The 95% confidence interval for the
      difference in pain score was -1.0 to +3.0. CONCLUSIONS: The low pain score in
      both groups suggests the effectiveness of distraction therapy, although factors
      such as skill of the operator and previous experience of the patient group are of
      relevance. There was no significant difference in the pain score between the EMLA
      and placebo groups, suggesting that in this age group if carefully selected
      children receive distraction during venepuncture EMLA may not be necessary.

PMID- 11236045
TI  - Oral sucrose compares favourably with lidocaine-prilocaine cream for pain relief
      during venepuncture in neonates.
AB  - To compare the relative efficacy of oral sucrose versus EMLA cream for pain
      relief during venepuncture, 51 full-term newborns (38M, 13F; postnatal age <4 d)
      in a stable condition were randomly allocated to one of four treatment groups:
      placebo (2 ml spring water); 2 ml sucrose 24% w/v; 1 g lidocaine-prilocaine 5%
      cream (EMLA); or EMLA plus sucrose. Water or a single dose of sucrose solution
      was administered orally 2 min before venepuncture. EMLA cream was applied in the
      antecubital fossa 45-60 min before venepuncture and covered by a Tegaderm
      dressing. A pacifier was given before skin puncture, but it was not actively held
      or replaced during the procedure or observation periods. In total, 55
      venepunctures were performed blindly, always for clinical reasons. As indicators
      of pain, the total crying time was recorded and heart rate, respiratory rate and
      arterial oxygen saturation were measured blindly at baseline, immediately post
      venepuncture, and 2 and 4 min afterwards. The main effects observed were: (i)
      time spent crying decreased significantly in the sucrose alone (p = 0.001) and
      EMLA plus sucrose (p = 0.008) groups; (ii) the above treatments attenuated
      significantly (p < 0.05) the immediate heart rate response to pain; and (iii) the
      concomitant use of EMLA did not increase further the analgesic efficacy of
      sucrose. CONCLUSION: This study shows that a 24% oral sucrose solution compares
      favourably with EMLA cream as a safe and cheap analgesic procedure to decrease
      pain responses to venepuncture in newborns.

PMID- 11236046
TI  - Prediction of hyperbilirubinaemia in the healthy term newborn.
AB  - The aim is to establish the correlation between transcutaneous bilirubin (TCB)
      and serum bilirubin (TSB) and its predictive value for significant
      hyperbilirubinaemia > or = 290 mcmol/L (17 mg/dL). We studied a total of 2004
      healthy full-term newborns, weight 3.230 g +/- 491 g; 90% received breast milk.
      The study was performed in two phases. In the first phase (610 newborns), the
      following tests were carried out: hematocrit and bilirubin in umbilical cord
      blood; TCB at 24 h, 48 h and between 60 h and 96 h at the forehead and over the
      sternum; TSB was measured along with this last test. In the second phase (1394
      newborns), the predictive value of TCB and TSB was validated. The incidence of
      bilirubin > or = 290 mcmol/L was 2.95% and 3.2%. The correlation between TSB and
      TCB is high (n = 996; r = 0.92; y = 5.916 + 0.804x; p < 0.000). There was a
      better correlation between TCB and TSB with sternal compared to forehead
      determination (< 24 h: 0.81 vs 0.77; 24-48 h: 0.887 vs 0.83; and > 48 h: 0.94 vs
      0.83). The study showed the scant sensitivity of umbilical cord blood bilirubin
      and good predictive value at 24 h of TSB > or = 102 mcmol/L (6 mg/dL) and at 48 h
      of TSB > or = 154 mcmol/L (9 mg/dL) and TCB > or = 13 (equivalent to 154
      mcmol/L). CONCLUSION: There is a good correlation between TCB and TSB. In infants
      with TSB > or = 102 mcmol/L at 24 h or TSB > or = 154 mcmol/L or transcutaneous
      readings > or = 13 h at 48 h, a TSB test must be performed after 48 h of life.

PMID- 11236047
TI  - Clinical aspects on neonatal cholestasis based on observations at a Swedish
      tertiary referral centre.
AB  - The aim of the study was to investigate the clinical aspects of neonatal
      cholestasis. The medical records of 85 cholestatic infants were retrospectively
      reviewed. A majority of the patients were referred from other parts of the
      country. The most common diagnoses were extrahepatic biliary atresia (n = 30
      patients), alpha1-antitrypsin deficiency (n = 11) and progressive familial
      intrahepatic cholestasis (n = 11). On presentation, the biliary atresia group had
      higher mean serum values of bilirubin, G-GT and cholesterol than the patients
      with intrahepatic cholestasis, with no significant differences noticed for any
      other biochemical parameter. A lack of excretion on hepatobiliary scintigraphy
      was noticed in all investigated patients with biliary atresia, but also in 9 of
      34 patients with intrahepatic neonatal cholestasis. There was no statistical
      correlation between the age at portoenterostomy and the outcome in patients with
      biliary atresia. However, both the detection of a partial flow on perioperative
      cholangiogram and the establishment of a non-icteric phase within 6 mo after the
      portoenterostomy correlated to a good outcome. Eight of 11 patients with
      progressive familial intrahepatic cholestasis were treated with a biliary
      diversion procedure, five of eight experienced a sustained cholestatic remission.
      CONCLUSIONS: Progressive familial intrahepatic cholestasis may be a more common
      cause of neonatal cholestasis in Sweden than reported elsewhere and that the
      experience with biliary diversion is positive. While early referral in patients
      with extrahepatic biliary atresia remains important, a portoenterostomy should be
      attempted also in patients referred after 3 mo of age.

PMID- 11236048
TI  - Detection of bacterial DNA by PCR and reverse hybridization in the 16S rRNA gene
      with particular reference to neonatal septicemia.
AB  - AIM: The clinical diagnosis of sepsis is difficult, particularly in neonates. It
      is necessary to develop a rapid and reliable method for detecting bacteria in
      blood and cerebrospinal fluid (CSF). Polymerase chain reaction (PCR) and reverse
      hybridization of the 16S rRNA gene would permit fast and sensitive determination
      of the presence of bacteria and differentiate gram-positive bacteria from gram
      negative ones in clinical specimens. METHODS: We developed a pair of primers
      according to the gene encoding 16SrRNA found in all bacteria. DNA fragments from
      different bacterial species and from clinical samples were detected with PCR, and
      with reverse hybridization using a universal bacterial probe, a gram-positive
      probe and a gram-negative probe. RESULTS: A 371 bp DNA fragment was amplified
      from 20 different bacterial species. No signal was observed when human DNA and
      viruses were used as templates. The sensitivity could be improved to 10(-12) g.
      All 26 culture-positive clinical samples (22 blood samples and 4 CSF samples)
      were positive with PCR. The gram-negative and gram-positive probes hybridized to
      clinical samples and to known bacterial controls, as predicted by Gram's stain
      characteristics. CONCLUSIONS: Our results suggest that the method of PCR and
      reverse hybridization is rapid, sensitive and specific in detecting bacterial
      infections. This finding may be significant in the clinical diagnosis of sepsis
      in neonates.

PMID- 11236049
TI  - Plasma levels of natriuretic peptides and hemodynamic assessment of patent ductus
      arteriosus in preterm infants.
AB  - The main purpose of this study was to investigate whether circulating natriuretic
      peptides in premature infants reflect the hemodynamic significance of a patent
      ductus arteriosus (PDA). The study comprises 120 examinations in 55 premature
      infants with a mean gestational age of 27.2 wk and a mean birthweight of 933 g.
      Based on clinical and echocardiographic findings, the hemodynamic influence of
      ductal shunting was classified as small, moderate or large. Blood samples for N
      terminal proatrial natriuretic peptide (Nt-proANP) and brain natriuretic peptide
      (BNP) were analysed after completion of the clinical part of the study. Linear
      regression indicated a very strong association between Nt-proANP and BNP
      (adjusted R = 0.89). The mean levels of Nt-proANP and BNP increased with the size
      of the shunt through a PDA, and peptide values followed hemodynamic alterations.
      The size of PDA accounted for 50% and 47% of the total variation in the plasma
      values of Nt-proANP and BNP, respectively. In detecting an echocardiographically
      significant PDA, the area under a ROC curve was 0.94 for Nt-proANP and 0.90 for
      BNP. CONCLUSION: The magnitude of shunting through a PDA is the main determinant
      of plasma levels of natriuretic peptides in premature infants. Nt-proANP and BNP
      seem to have the same pattern of secretion. Our findings indicate that
      measurements of natriuretic peptides may provide clinically relevant information
      in the hemodynamic assessment of premature infants.

PMID- 11236050
TI  - Patent ductus venosus does not lead to alimentary galactosaemia in preterm
      infants.
AB  - The aim of this study was to investigate if an open ductus venosus representing a
      portal-caval shunt can lead to transient "alimentary galactosaemia" in preterm
      infants fed human breast milk. Twenty-six preterm infants (28-34 wk of
      gestational age) with open ductus venosus were included. Capillary blood samples
      for measurement of galactose and glucose were collected before, 30 and 50 min
      after a meal with breast milk (range 12-23 mL/kg). Ultrasound studies of the
      blood flow in the ductus venosus, truncus coeliacus, superior mesenteric artery
      and left hepatic vein were performed before and 30 min after the meal. There was
      a significant rise in blood glucose after 30 and 50 min, indicating a sufficient
      lactose load. Galactose, however, was either not detectable or was just above the
      detectable limit (0.1-0.4 mmol/L), with no changes after the meal. An increased
      flow velocity was found in the ductus venosus and superior mesenteric artery
      after 30 min (p < or = 0.001) indicating increased entero-hepatic and portal
      caval shunting. CONCLUSION: A patent ductus venosus does not lead to a
      significant hypergalactosaemia in preterm infants fed human breast milk. Thus, in
      respect to breast-milk feeding, this is regarded safe in healthy preterm infants
      even with an open ductus venosus. The increased portal-caval shunting may,
      however, influence the hepatic metabolism of other enterally absorbed substances.

PMID- 11236051
TI  - Hydrolysed protein accelerates the gastrointestinal transport of formula in
      preterm infants.
AB  - Vomiting, large gastric residuals and abdominal distension are common in very
      immature infants on formula feeding. The present trial investigated whether a
      protein hydrolysate formula reduces the gastrointestinal transit time in preterm
      infants. Fifteen preterm infants (median gestational age 29 (24-32) wk,
      birthweight 1241 (660-1900) g, postnatal age 18 (5-54) d) on full enteral feeds
      (>150 ml/kg*d) were enrolled. It was hypothesized that the gastrointestinal
      transit time is at least 2 h shorter when protein hydrolysate formula is fed
      compared with standard preterm formula. In a randomized cross-over design study,
      each formula was fed for 5 d. On days 4 and 9 the gastrointestinal transit time
      was estimated using carmine red. The protein hydrolysate formula had a markedly
      shorter gastrointestinal transit time (9.8 h) than the standard formula (19 h) (p
      = 0.0022, two-sided Mann-Whitney U test). CONCLUSION: The hydrolysate protein
      formula accelerated gastrointestinal transit of milk and stools, but whether
      hydrolysate formulas enable a more rapid establishment of full enteral feeding in
      preterm infants needs to be investigated.

PMID- 11236052
TI  - Linguistic skills at 6 1/2 years of age in children who required neonatal
      intensive care in 1986-1989.
AB  - Linguistic skills at 6 1/2 y of age, corrected for gestational age at birth, were
      examined in a cohort of 230 children who had required neonatal intensive care
      (NIC) in 1986-89, and in 71 fullterm neonatally healthy control children (C)
      matched to the NIC children born at < 32 gestational weeks. Ten linguistic areas
      were assessed. The 10th percentile score of the controls was identified in each
      linguistic area and used for comparisons. In 77.5% of the controls and 63.5% of
      the NIC children, no score was lower than the 10th percentile score of the
      controls. Scores lower than the 10th percentile score were more common in NIC
      children born at term or at 23-31 wk, and within this group of children those
      born at 23-27 wk, than in controls. CONCLUSION: In preterm children of < 32 wk
      the results in the linguistic areas of imitation of articulatory positions,
      comprehension of logical grammatical constructions, phonemes and word fluency
      differed from those of the matched controls, and in NIC children born at > or =
      32 weeks the results for imitation of articulatory positions, articulatory
      patterns and sentences, auditory discrimination and word fluency were poorer than
      those of the controls.

PMID- 11236053
TI  - Utilization of healthcare by very-low-birthweight infants during their first year
      of life.
AB  - New knowledge in perinatal medicine has resulted in increased survival of very
      low-birthweight (VLBW) infants. After leaving hospital, the child is seen at
      regular medical check-ups, but there is often a persistent worry about the child
      which affects the family as a whole. This can lead to an increased utilization of
      healthcare. Our objective was therefore to describe the utilization of healthcare
      by VLBW infants during their first year of life and its relation to high-risk
      diagnoses in the neonatal period. The study group comprised 36 infants born at
      gestational ages of < or = 31 wk and with a birthweight of < or = 1500 g, and was
      compared with a control group of 36 full-term infants. Utilization of healthcare
      by the VLBW infants was higher than that by the control group in paediatric and
      ophthalmic outpatient clinics. The total number of contacts with healthcare was
      on average 38.7 versus 17.4. High-risk diagnoses in the neonatal period did not
      correlate with utilization of care, except for visits to the paediatric
      outpatient clinic, especially planned visits. Further studies focusing on how to
      support these families after leaving hospital are therefore needed.

PMID- 11236054
TI  - Neurological development up to the age of four years of extremely low birthweight
      infants born in Southern Finland in 1991-94.
AB  - A total of 142 infants with birthweights of less than 1000 g were examined at the
      age of 4 y by a child neurologist, by a neuropsychologist and by an occupational
      therapist in order to establish the rate of neurological disorders. A total of 57
      (40%) of the children had normal neurological development, 52 (37%) had minor
      neurological disorders, 27 (19%) were diagnosed with cerebral palsy, and 6 (4%)
      were mentally retarded (IQ <71) with no motor disability. The rate of cerebral
      palsy was identical with the figure at age 2 y, but the rate of minor
      neurological disorders increased from 25% to 37%. Compared with international
      rates, we found a higher rate of cerebral palsy, but the incidence of minor
      neurological disorders corresponded with figures published previously.

PMID- 11236055
TI  - Associations of age and gender with activity and sleep.
AB  - Associations between age/gender and activity/sleep (measured by actigraphs) in 66
      healthy children aged 5-12 y were studied. With increasing age, daytime motor
      activity and total sleep time decreased and activity pattern changed. No gender
      differences were found. It was concluded that in this age group there is an age
      dependent change in the amount and pattern of motor activity and sleep due to
      developmental and/or environmental factors.

PMID- 11236056
TI  - Evaluation of serum lipoprotein(a) levels in Greek schoolchildren.
AB  - This study aimed to provide associations of age and gender with serum
      lipoprotein(a) [Lp(a)] levels and percentile distribution data for Greek
      children. In total, 3298 children (1590M, 1708F, aged 6-14 y) participated in the
      study. Lp(a) levels were evaluated with an immunosorbent assay. Mean Lp(a) levels
      were 153-157 mg l(-1) for boys and 146-151 mg l(-1) for girls, and median levels
      133-139 mg l(-1) for boys and 100-108 mg l(-1) for girls. CONCLUSION: The Lp(a)
      levels in these children were the lower ever reported. These results suggest that
      the young Greek population is not at high risk of developing coronary heart
      disease as a result of high Lp(a) levels.

PMID- 11236057
TI  - Reed-Sternberg cells in atypical primary EBV infection.
AB  - The presence of Epstein-Barr virus (EBV) in the Hodgkin's/Reed-Sternberg (HRS)
      cells of a significant proportion of cases of Hodgkin's lymphoma (HL) is a matter
      of consideration when a case of presumptive HL has to be differentiated from
      infectious mononucleosis (IM). A 15-y-old boy was admitted with a presumptive
      diagnosis of extranodal HL, based on the biopsy of a painless ulcer on the right
      mandibular alveolar crest. Histologic examination of the lesion was consistent
      with mixed cellularity HL. The patient additionally presented with
      hepatosplenomegaly and regional lymphadenopathy. Serology for EBV was indicative
      of acute infection. Histological examination of regional lymphoid tissue was
      consistent with immunologic activation due to primary EBV infection. The patient
      was left untreated, under close observation. All clinical findings resolved
      within 3 mo and EBV viral capsid antigen (VCA) IgM antibodies converted to
      negative after 6 mo. A 3-y follow-up period was uneventful.

PMID- 11236058
TI  - Neurological features in Gaucher's disease during enzyme replacement therapy.
AB  - This report describes two patients with Gaucher's disease who had unusual
      clinical symptoms during enzyme replacement therapy. One patient was a female
      with type 3 Gaucher's disease. She developed a pericardial effusion at 7 y of
      age, which contained many Gaucher cells despite enzyme replacement therapy. She
      died from neurological deterioration during enzyme replacement therapy, despite
      an improvement in her visceral manifestations. The other patient is a male with
      type 2 Gaucher's disease, who has achieved long-term survival after being
      supported by mechanical ventilation and enzyme replacement therapy. While on
      enzyme replacement therapy at the age of 4 y, he suffered a generalized cutaneous
      disease which was clinically diagnosed as ichthyosis. CONCLUSION: These cases
      suggest that ordinary enzyme replacement therapy is insufficient for some of the
      non-neurological manifestations of severe types of Gaucher's disease.

PMID- 11236059
TI  - 13C-urea breath test in children with Helicobacter pylori infection: validity of
      the use of a mask to collect exhaled breath samples.

PMID- 11236060
TI  - Streptococcus milleri as a cause of pulmonary abscess.

PMID- 11236061
TI  - Probable case of autoimmune hepatitis without usually known serologic markers in
      a 6-year-old boy.

PMID- 11236062
TI  - Pearson's syndrome: a multisystem disorder.

PMID- 11236063
TI  - The functions of the amyloid precursor protein gene.
AB  - The amyloid precursor protein (APP) gene and its protein products have multiple
      functions in the central nervous system and fulfil criteria as neuractive
      peptides: presence, release and identity of action. There is increased
      understanding of the role of secretases (proteases) in the metabolism of APP and
      the production of its peptide fragments. The APP gene and its products have
      physiological roles in synaptic action, development of the brain, and in the
      response to stress and injury. These functions reveal the strategic importance of
      APP in the workings of the brain and point to its evolutionary significance.

PMID- 11236064
TI  - Memory-forming chemical reactions.
AB  - We address in this review the various types of chemical reactions that underlie
      memory storage in biological systems. Using examples from both invertebrate and
      mammalian learning systems, we describe three types of memory-storing reactions:
      short-term reactions mediated by transient changes in second messenger levels,
      long-term reactions mediated by species with long half lives, and ultralong-term
      or mnemogenic reactions that can store memory indefinitely, even in the face of
      ongoing turnover of the molecules involved.

PMID- 11236065
TI  - Progress in understanding the factors regulating reversibility of long-term
      potentiation.
AB  - Over the past two decades there has been a progressive understanding of the
      properties and mechanisms underlying long-term potentiation (LTP) of synaptic
      efficacy, a putative mechanism for learning and memory storage in the brain.
      Although LTP is remarkable for its stability, recent work has provided evidence
      that various manipulations can disrupt LTP if applied shortly after its
      induction. This kind of reversal of synaptic strength from the potentiated state
      to pre-LTP levels is termed depotentiation. Depotentiation of LTP is effectively
      induced by low-frequency afferent stimulation (1-5 Hz), brief periods of hypoxia,
      application of adenosine receptor agonists and brief cooling shocks. The examples
      of depotentiation described to date are input specific, and not differently
      expressed during development. The mechanisms responsible for this phenomenon
      remain to be fully characterized, although some possibilities are dependent on
      NMDA receptor activation, the increases in intracellular Ca2+, and altered states
      of protein kinases or phosphatases. In this review, we summarize the recent data
      concerning putative depotentiation mechanisms and the implications of this
      phenomenon in the mechanisms of "forgetting", and discuss the prevention of
      saturation of the storage capacity of a neuronal network.

PMID- 11236066
TI  - Viral vectors for gene therapy in Parkinson's disease.
AB  - The ability of transplanted neurons from aborted foetuses to produce some
      therapeutic benefit in Parkinson's disease makes this disease an obvious target
      for the development of gene therapy procedures which involve delivering the same
      factors as are provided by the foetal neurons but using a reagent which could be
      produced in large amounts in a standardised manner. This approach could involve
      both the delivery of the gene encoding tyrosine hydroxylase to boost dopamine
      production or the delivery of genes encoding neurotrophic factors such as GDNF to
      promote the survival of dopaminergic neurons. A variety of different viral and
      non-viral methods for achieving such gene delivery has been described. These are
      discussed together with the particular advantages of herpes simplex virus-based
      vectors which have the potential to deliver multiple therapeutic genes in a
      single virus vector.

PMID- 11236067
TI  - Trophic dependencies of rodent corticospinal neurons.
AB  - According to the classical neurotrophin hypothesis, neuronal survival is
      regulated by limited access to target-derived neurotrophic substances. Recent
      studies have indicated that this regulation is more complex than originally
      thought. First, neurons are not only supported by target-derived molecules but
      also via anterograde, paracrine, and autocrine mechanisms. Second, phenotypes of
      neurotrophic factor-/receptor-mutant animals displayed fewer neuronal deficits
      than predicted, suggesting interactivity and redundancy of trophic support of
      neurons. Finally, certain neurotrophins, in addition to their survival-promoting
      action, are able to induce neuronal death. Observations in the corticospinal
      system support the general applicability of these concepts and provide additional
      insights into the integrative mode of neuronal survival regulation. CNTF and GDNF
      support developing corticospinal neurons (CSN) by direct mechanisms, while the
      effects of NT-4/5 require cell contacts of CSN with other cortical neurons in
      vitro. Thus, these effects do not merely reflect trophic redundancy but the
      ability of CSN to integrate survival signals of growth factors from different
      families via different pathways. CNTF and GDNF also promote survival of adult
      axotomized CSN in vivo. Virtually all adult CSN express mRNA coding for the NT-3
      receptor TrkC and the BDNF-receptor TrkB, and after axotomy, CSN also express
      mRNA for the common neurotrophin-receptor p75NTR, suggesting a role of endogenous
      neurotrophins for survival regulation of CSN. Indeed, most axotomized CSN depend
      on endogenous BDNF for survival, and endogenous NT-3 promotes the death of BDNF
      dependent CSN. NT-3-mediated death-induction requires co-signalling of TrkC- and
      p75NTR-receptors. With BDNF/TrkB promoting survival and NT-3/TrkC/p75NTR
      promoting death, CSN integrate at least three different neurotrophin/receptor
      signals for death/survival decisions.

PMID- 11236068
TI  - Fixed-dosed risperidone in mania: an open experimental trial.
AB  - The purpose of the study was to assess the efficacy and tolerance of risperidone
      in mania. Fourteen inpatients with a DSM-IV manic episode were treated with
      risperidone at a fixed daily dose of 6 mg for 4 weeks. Compliance was assured by
      weekly determinations of serum concentrations of risperidone. Ten out of the 14
      patients completed all 4 weeks of treatment, and all of these achieved at least a
      75% reduction on the Bech-Rafaelsen Mania Scale (MAS). On the other applied
      measures, a substantial improvement was also seen in most patients, and no
      worsening in any of the rating scales was observed in any patient. Five patients
      continued concomitant treatment with a mood stabilizer. When the results were
      compared with the results from a similar historic control group treated with the
      middle-potency typical antipsychotic zuclopenthixol at a daily dose of 20 mg
      under the same experimental conditions, a between group difference in mean
      percentage change (baseline versus endpoint) on the MAS was 34.7% (95% confidence
      interval = 7.9-61.6%) in favour of risperidone. Side-effect profiles were rather
      similar in the two treatment groups. Despite design limitations, these findings
      may justify the conduction of randomized controlled trials to investigate the use
      of risperidone in mania.

PMID- 11236069
TI  - Pindolol augmentation in aggressive schizophrenic patients: a double-blind
      crossover randomized study.
AB  - Treatment of aggression in schizophrenic patients is a major challenge. We sought
      to examine the efficacy of augmentation of antipsychotic treatment with pindolol
      in the amelioration of aggression. Thirty male inpatients meeting DSM-IV criteria
      for schizophrenia, aged 20-65 years involved in four or more aggressive incidents
      in the two previous months, were enrolled in a double-blind crossover study.
      Aggression was evaluated per incident, with the Overt Aggression Scale (OAS).
      Positive and Negative Syndrome Scale (PANSS) was administered at baseline,
      crossover and at endpoint. Patients received either pindolol or placebo
      augmentation 5 mg x three times a day until crossover, then switched. No
      significant differences were found in the PANSS scores between the placebo and
      pindolol treatments. OAS scores were significantly reduced for number of
      aggressive incidents towards objects and other persons during pindolol treatment
      (0.59 versus 1.46, F = 6.09, P < 0.02; 1.96 versus 3.23, F = 4.17, P < 0.05,
      respectively). Similar results were obtained for severity of incidents (0.89
      versus 3.58, F = 19.42, P < 0.0001; 2.89 versus 6.85, F = 10.11, P < 0.004,
      respectively). Pindolol, with its dual beta and 5-HT1A blocking effect
      ameliorated both number and severity of aggressive acts. Influence on severity
      may be associated with a 5-HT1A antagonistic effect.

PMID- 11236070
TI  - Dose-dependent olanzapine-associated leukopenia: three case reports.
AB  - Leukopenia and agranulocytosis are well reported and dangerous haematological
      side-effects associated with the use of typical and atypical antipsychotics.
      These potentially life-threatening phenomena have led to treatment
      discontinuation and the consequent reemergence of psychiatric symptoms. We report
      three cases of patients who developed leukopenia during olanzapine treatment. In
      each case, the leukopenia was dose-dependent. Reduction in the dose of olanzapine
      was followed by normalization of the white blood count which allowed continuation
      of the medication. These cases suggest the possibility that, in some patients,
      leukopenia or agranulocytosis during olanzapine treatment might be dose-related.
      Thus, olanzapine dose reduction may permit treatment continuation where this is
      clinically indicated. In our cases, haematological side-effects were
      satisfactorily controlled by dose reduction without allowing the reemergence of
      psychiatric symptoms. This clinical management may offer an alternative to
      treatment suspension. A careful monitoring of the white blood count is obviously
      recommended. Olanzapine may be considered a potential and safer treatment for a
      this specific group of patients.

PMID- 11236071
TI  - Atypical antipsychotics and hyperglycaemia.
AB  - Hyperglycaemia is known occasionally to occur with conventional neuroleptics, but
      has more recently been associated with atypical antipsychotics especially
      clozapine and olanzapine. This article examines more closely this association. A
      review of relevant published literature from 1970 to date was undertaken
      following Medline and Embase searches in June 2000. Hyperglycaemia with clozapine
      was widely reported: spontaneous reports of either hyperglycaemia or ketoacidosis
      were described in a total of 17 people. In a five-year naturalistic study, 30.5%
      of patients taking clozapine were eventually diagnosed with Type 2 diabetes. With
      olanzapine, a total of 10 cases of hyperglycaemia and 5 cases of ketoacidosis
      have been published. Reports of hyperglycaemia with other atypicals are
      relatively scarce. The association of hyperglycaemia or ketoacidosis with
      clozapine and olanzapine appears to be a true drug-induced effect. Risk factors
      may include male gender, age of around 40 years and being non-Caucasian. The
      management of hyperglycaemia depends on the causative agent. With clozapine,
      treatment with oral hypoglycaemics has been successful. With olanzapine, other
      atypical antipsychotics may be considered. Blood glucose monitoring is essential
      for all patients starting clozapine or olanzapine.

PMID- 11236072
TI  - Citalopram 20 mg, 40 mg and 60 mg are all effective and well tolerated compared
      with placebo in obsessive-compulsive disorder.
AB  - Serotonin reuptake inhibitors appear to be uniquely effective treatments for
      obsessive-compulsive disorder (OCD). This double-blind, placebo-controlled study
      was the first trial to assess the efficacy of the most selective of the serotonin
      reuptake inhibitors, citalopram, in OCD. A total of 401 patients were randomized
      to receive citalopram 20, 40 or 60 mg/day or placebo for 12 weeks. All three
      doses of citalopram were significantly more effective than placebo measured on
      the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) change score (P < 0.01). The
      highest response rate, defined as 25% improvement in Y-BOCS entry score, was
      observed in the 60 mg group (65%). This compared with 52% and 57.4% in the 40 mg
      and 20 mg groups. Response rate on placebo was 36.6% (P < 0.05 for all three
      doses of citalopram compared to placebo). There was no significant difference
      between the individual doses of citalopram. An advantage was seen for citalopram
      on the Sheehan Disability Scale compared with placebo (P < 0.05 on all three
      citalopram groups versus placebo for both the work situation and the family life
      and home responsibilities and P < 0.05 on citalopram 60 mg and 20 mg versus
      placebo for the social life and home activities). Citalopram was well tolerated;
      only 4 to 6 patients in each dose group discontinued the study prematurely due to
      adverse events.

PMID- 11236073
TI  - Efficacy of mirtazapine add on therapy to haloperidol in the treatment of the
      negative symptoms of schizophrenia: a double-blind randomized placebo-controlled
      study.
AB  - The negative symptoms of schizophrenia remain a major clinical challenge.
      Mirtazapine is an antidepressant with antagonist properties at 5-HT2A, 5-HT3 and
      alpha 2 receptors as well as indirect 5-HT1a agonist effects. Many of these
      pharmacological actions have clinical or preclinical evidence of efficacy in
      schizophrenia. This study was a 6-week randomized placebo-controlled trial of
      mirtzepine or placebo add on to haloperidol 5 mg in the treatment of 30 patients
      with DSM-IV schizophrenia. The primary finding of the trial was a 42% reduction
      in Positive and Negative Syndrome Scale (PANSS) negative symptom scores in the
      mirtazapine group compared to placebo at the end of 6 weeks (mirtazapine 13.9, SD
      1.56; placebo 23.9, SD 1.56; P = 0.000, F = 20.31, d.f. = 1). The PANNS total
      scores, Clinical Global Impression severity and improvement scales in addition
      showed superiority of mirtazapine over placebo. There was no difference between
      the groups on the Hamilton depression scale at endpoint, suggesting that the
      improvement in negative symptoms was not an artifact of mood improvement. These
      results suggest a potential role for mirtazapine in the negative symptoms of
      schizophrenia.

PMID- 11236075
TI  - Speciation of platinum compounds: a review of recent applications in studies of
      platinum anticancer drugs.
AB  - This is a review of investigations involving speciation studies of five important
      platinum-containing drugs used in cancer treatments. The information presented
      here is drawn from recent reports published during the period 1995-1999. The work
      includes detection, separations and identifications of degradation and
      biotransformation products. In addition, important information is reported on the
      number and nature of products of reactions of platinum anticancer drugs with
      thiol compounds. HPLC is employed effectively for separations of reaction
      products in speciation investigations. Information derived from speciation is
      very helpful in studies of pharmacokinetics as well as side effects and
      toxicities of the drugs as they are administered to patients.

PMID- 11236074
TI  - Serotonergic function in major depression and effect of sertraline and paroxetine
      treatment.
AB  - We investigated platelet [14C]serotonin (5-HT) uptake and lysergic acid
      diethylamide [N-methyl-3H] ([3H]LSD)- and phenyl-6'-paroxetine ([3H]paroxetine)
      binding in 30 patients with major depression at baseline and after 6 months of
      treatment with either paroxetine or sertraline. The study was of a double-blind
      design. Baseline data was compared with an age- and gender-matched group of
      healthy volunteers. Baseline Vmax was significantly lower in patients than in
      controls. Bmax for [3H]paroxetine binding were similar in patients and controls,
      but patients who suffered their first depression had significantly lower Bmax for
      [3H]paroxetine binding than patients who had suffered multiple depressions.
      Twenty-three patients (76%) (13 in the paroxetine group and 10 in the sertraline
      group) responded to treatment as judged by a 50% or more reduction in Montgomery
      Asberg Depression Rating Scale (MADRS) scores after 6 months of treatment. There
      were no significant differences between the paroxetine and sertraline treated
      groups. Both paroxetine and sertraline caused a significant reduction in Vmax and
      a significant increase in Km. There was a strong correlation between Km and
      plasma drug concentration in patients who experienced their first depression but
      not in patients who had suffered multiple episodes. Bmax for [3H]paroxetine
      binding increased after paroxetine treatment while the opposite occurred after
      sertraline treatment. There was a significant interaction between the impact of
      drug and earlier depressions. All patients included in the study had been drug
      free for at least 2 months. Earlier antidepressant treatment may have long
      withstanding effects on the serotonin uptake machinery but it cannot be excluded
      that the sensitivity of the uptake mechanism may become more resistant to change
      in patients with recurrent depressive episodes.

PMID- 11236076
TI  - Gas chromatographic-mass spectrometric determination of alpha-ketoisocaproic acid
      and [2H7]alpha-ketoisocaproic acid in plasma after derivatization with N-phenyl
      1,2-phenylenediamine.
AB  - A method for determination of alpha-ketoisocaproic acid (KIC) and [4,5,5,5,6,6,6
      2H7]alpha-ketoisocaproic acid ([2H7]KIC) in rat plasma was developed using gas
      chromatography-mass spectrometry-selected ion monitoring (GC-MS-SIM). [5,5,5
      2H3]alpha-Ketoisocaproic acid ([2H3]KIC) was used as an analytical internal
      standard to account for losses associated with the extraction, derivatization and
      chromatography. The keto acids were extracted by cation-exchange chromatography
      using BondElut SCX cartridge and derivatized with N-phenyl-1,2-phenylenediamine
      to form N-phenylquinoxalinone derivatives. Quantitation was performed by SIM of
      the respective molecular ions at m/z 278, 281 and 285 for the derivatives of KIC,
      [2H3]KIC and [2H7]KIC on the electron impact method. The limit of detection was
      found to be 70 fmol per injection (S/N=3) and the limit of quantitation for
      [2H7]KIC was around 50 nM in rat plasma. Endogenous KIC concentrations in 50
      microl of rat plasma were measured with relative intra- and inter-day precision
      of 4.0% and 3.3%, respectively. The intra- and inter-day precision for [2H7]KIC
      spiked to rat plasma in the range of 0.1 to 10 microM gave good reproducibility
      with relative standard deviation (RSD) of 6.5% and 5.4%, respectively. The intra-
      and inter-day relative errors (RE) for [2H7]KIC were less than 6.4% and 3.8%,
      respectively. The method was applied to determine the plasma concentration of
      [2H7]KIC after an intravenous administration of [2H7]KIC in rat.

PMID- 11236077
TI  - A validated high-performance liquid chromatographic assay for the simultaneous
      determination of denaverine and its N-monodemethyl metabolite in human plasma.
AB  - An isocratic reversed-phase high-performance liquid chromatographic method for
      the simultaneous determination of denaverine and its N-monodemethyl metabolite
      (MD 6) in human plasma is described. The assay involves the extraction with an n
      heptane-2-propanol mixture (9:1, v/v) followed by back extraction into 12.5%
      (w/w) phosphoric acid. The analytes of interest and the internal standard were
      separated on a Superspher RP8 column using a mobile phase of acetonitrile-0.12 M
      NH4H2PO4-tetrahydrofuran (24:17.2:1, v/v), adjusted to pH 3 with 85% (w/w)
      phosphoric acid. Ultraviolet detection was used at an operational wavelength of
      220 nm. The retention times of MD 6, denaverine and the internal standard were
      5.1, 6.3 and 10.2 min, respectively. The assay was validated according to
      international requirements and was found to be specific, accurate and precise
      with a linear range of 2.5-150 ng/ml for denaverine and MD 6. Extraction
      recoveries for denaverine and MD 6 ranged from 44 to 49% and from 42 to 47%,
      respectively. The stability of denaverine and MD 6 in plasma was demonstrated
      after 24 h storage at room temperature, after three freeze-thaw cycles and after
      7 months frozen storage below -20 degrees C. The stability of processed samples
      in the autosampler at room temperature was confirmed after 24 h storage. The
      analytical method has been applied to analyses of plasma samples from a
      pharmacokinetic study in man.

PMID- 11236078
TI  - Determination of high-energy phosphate compounds and inorganic phosphate by
      reversed-phase high-performance liquid chromatography: evaluation of myocardial
      metabolic status in aerobically perfused and hypoxic mouse heart.
AB  - The present paper describes a simple HPLC method designed for measuring high
      energy phosphate (HEP) compounds in a single run and inorganic phosphate (Pi) in
      an other short run under the same HPLC conditions. Inorganic phosphate was
      estimated by using thymidine phosphorylase (EC 2.4.2.4) which catalyzes a
      reaction involving inorganic phosphate to produce 2-deoxyribose 1-phosphate and
      thymine. The thymine/Pi stoichiometry was 1. The method provides a reproducible
      instrument for evaluating myocardial high-energy metabolism under physiological
      and pathological conditions.

PMID- 11236079
TI  - High-throughput, semi-automated determination of a cyclooxygenase II inhibitor in
      human plasma and urine using solid-phase extraction in the 96-well format and
      high-performance liquid chromatography with post-column photochemical
      derivatization-fluorescence detection.
AB  - Compound I, 5-chloro-3-(4-methanesulfonylphenyl)-6'-methyl-[2,3']bipyridinyl, has
      been found to be a specific inhibitor of the enzyme cyclooxygenase II (COX II).
      The anti-inflammatory properties of this compound are currently being
      investigated. HPLC assays for the determination of this analyte in human plasma
      and human urine have been developed. Isolation of I and the internal standard
      (II) was achieved by solid-phase extraction (SPE) in the 96-well format. A C8 SPE
      plate was used for the extraction of the drug from human plasma (recovery >90%)
      while a mixed-mode (C8/Cation) SPE plate was used to isolate the analytes from
      human urine (recovery approximately 71%). The analyte and internal standard were
      chromatographed on a Keystone Scientific Prism-RP guard column (20 x 4.6 mm)
      connected to a Prism-RP analytical column (150 x 4.6 mm), using a mobile phase
      consisting of 45% acetonitrile in 10 mM acetate buffer (pH = 4); the analytes
      eluted at retention times of 5.2 and 6.9 min for I and II, respectively.
      Compounds I and II were found to form highly fluorescent products after exposure
      to UV light (254 nm). Thus, the analytes were detected by fluorescence
      (lambda(ex) = 260 nm, lambda(em) =375 nm) following post-column photochemical
      derivatization. Eight point calibration curves over the concentration range of 5
      500 ng/ml for human plasma and human urine yielded a linear response (R2>0.99)
      when a 1/y weighted linear regression model was employed. Based on the replicate
      analyses (n = 5) of spiked standards, the within-day precision for both assays
      was better than 7% C.V. at all points on the calibration curve; within-day
      accuracy was within 5% of nominal at all standard concentrations. The between-run
      precision and accuracy of the assays, as calculated from the results of the
      analysis of quality control samples, was better than 8% C.V. and within 8% of
      nominal. I was found to be stable in human plasma and urine for at least 8 and 2
      months, respectively. In addition, the human plasma assay was semi-automated in
      order to improve sample throughput by utilizing a Packard liquid handling system
      and a Tom-Tec Quadra 96 SPE system. The precision and accuracy of the semi
      automated procedure were comparable to the manual procedure. Over 5000 clinical
      samples have been analyzed successfully using these methods.

PMID- 11236080
TI  - High-performance liquid chromatographic determination of oxolinic acid and
      flumequine in the live fish feed artemia.
AB  - A high-performance liquid chromatography (HPLC) analytical method for the
      determination of oxolinic acid and flumequine in Artemia nauplii is described.
      The samples were extracted and cleaned up by a solid-phase extraction (SPE)
      procedure using SPE C18 cartridges. Oxolinic acid and flumequine were determined
      by reversed-phase HPLC using a mobile phase of methanol-0.1 M phosphate buffer,
      pH 3 (45:55, v/v) and a UV detection wavelength of 254 nm. Calibration curves
      were linear for oxolinic acid in the range of 0.2-50 microg/g (r2=0.9998) and for
      flumequine in the range of 0.3-50 microg/g (r2=0.9994). Mean recoveries amounted
      to 100.8% and 98.4% for oxolinic acid and flumequine, respectively. The
      quantification limit was 0.2 microg/g for oxolinic acid and 0.3 microg/g for
      flumequine. Quantitative data from an in vivo feeding study indicated excellent
      uptake of both drugs by Artemia nauplii.

PMID- 11236081
TI  - Modified method for the determination of capillary electrophoresis nitric oxide
      correlated nitrate in tissue homogenates.
AB  - A modified capillary electrophoretic method for the determination of nitric oxide
      correlated nitrate in several tissue homogenates is described in this study. The
      method was developed using a running buffer consisting of 200 mM lithium chloride
      and 10 mM borate buffer at pH 8.5, in a fused-silica column total 82 cm,
      effective 43 cm length and 75 microm I.D. The signal was measured at 214 nm and
      controlled current of 200 microA (equivalent to 12.7 kV) was applied in the
      reversed polarity direction. The sample was injected by vacuum pressure 50 ms (25
      nl). In these conditions, bromide as internal standard and nitrate appeared at
      7.2 and 8.9 min, respectively. Whole validation procedures were applied and
      satisfactory results were obtained. The nitrate levels of the tissue homogenates
      of control and L-NAME applied (heart, brain, kidney, stomach, lung, testis and
      liver) were monitored by the present method and it was decided that the method is
      precise and accurate.

PMID- 11236082
TI  - Determination of retinol and retinyl esters in human plasma by high-performance
      liquid chromatography with automated column switching and ultraviolet detection.
AB  - A HPLC method with automated column switching and UV detection is described for
      the simultaneous determination of retinol and major retinyl esters (retinyl
      palmitate, retinyl stearate, retinyl oleate and retinyl linoleate) in human
      plasma. Plasma (0.2 ml) was deproteinized by adding ethanol (1.5 ml) containing
      the internal standard retinyl propionate. Following centrifugation the
      supernatant was directly injected onto the pre-column packed with LiChrospher 100
      RP-18 using 1.2% ammonium acetate-acetic acid-ethanol (80:1:20, v/v) as mobile
      phase. The elution strength of the ethanol containing sample solution was reduced
      by on-line supply of 1% ammonium acetate-acetic acid-ethanol (100:2:4, v/v). The
      retained retinol and retinyl esters were then transferred to the analytical
      column (Superspher 100 RP-18, endcapped) in the backflush mode and
      chromatographed under isocratic conditions using acetonitrile-methanol-ethanol-2
      propanol (1:1:1:1, v/v) as mobile phase. Compounds of interest were detected at
      325 nm. The method was linear in the range 2.5-2000 ng/ml with a limit of
      quantification for retinol and retinyl esters of 2.5 ng/ml. Mean recoveries from
      plasma were 93.4-96.5% for retinol (range 100-1000 ng/ml) and 92.7-96.0% for
      retinyl palmitate (range 5-1000 ng/ml). Inter-assay precision was < or =5.1% and
      < or =6.3% for retinol and retinyl palmitate, respectively. The method was
      successfully applied to more than 2000 human plasma samples from clinical
      studies. Endogenous levels of retinol and retinyl esters determined in female
      volunteers were in good accordance with published data.

PMID- 11236083
TI  - Analysis of benzphetamine and its metabolites in rat urine by liquid
      chromatography-electrospray ionization mass spectrometry.
AB  - An analytical method to identify and determine benzphetamine (BMA) and its five
      metabolites in urine was developed by liquid chromatography-electrospray
      ionization mass spectrometry (LC-ESI-MS) using the solid-phase extraction column
      Bond Elut SCX. Deuterium-labeled compounds, used as internal standards, were
      separated chromatographically from each corresponding unlabeled compound in the
      alkaline mobile phase with an alkaline-resistant ODS column. This method was
      applied to the identification and determination of BMA and its metabolites in rat
      urine collected after oral administration of BMA. Under the selected ion
      monitoring mode, the limit of quantitation (signal-to-noise ratio 10) for BMA, N
      benzylamphetamine (BAM), p-hydroxybenzphetamine (p-HBMA), p-hydroxy-N
      benzylamphetamine (p-HBAM), methamphetamine (MA) and amphetamine (AM) was 700 pg,
      300 pg, 500 pg, 1.4 ng, 6 ng and 10 ng in 1 ml of urine, respectively. This
      analytical method for p-HBMA, structurally closer to the unchanged drug of all
      the metabolites, was very sensitive, making this a viable metabolite for
      discriminating the ingestion of BMA longer than the parent drug or other
      metabolites in rat.

PMID- 11236084
TI  - Rapid determination of ranitidine in human plasma by high-performance liquid
      chromatography without solvent extraction.
AB  - A simple high-performance liquid chromatographic procedure was developed for the
      determination of ranitidine in human plasma. The method entailed direct injection
      of the plasma samples after deproteination using perchloric acid. The
      chromatographic separation was accomplished with an isocratic elution using
      mobile phase consisting of 21 mM disodium hydrogen phosphate-triethylamine
      acetonitrile (1000:60:150, v/v), pH 3.5. Analyses were run at a flow-rate of 1.3
      ml/min using a microbondapak C18 column and ultraviolet detection at a wavelength
      of 320 nm. The method was specific and sensitive, with a quantification limit of
      approximately 20 ng/ml and a detection limit of 5 ng/ml at a signal-to-noise
      ratio of 3:1. The mean absolute recovery was about 96%, while the within- and
      between-day coefficient of variation and percent error values of the assay method
      were all less than 8%. The linearity was assessed in the range of 20-1000 ng/ml
      plasma, with a correlation coefficient of greater than 0.999. This method has
      been used to analyze several hundred human plasma samples for bioavailability
      studies.

PMID- 11236085
TI  - Simple method for clinical determination of 13 carotenoids in human plasma using
      an isocratic high-performance liquid chromatographic method.
AB  - We report a reversed-phase high-performance liquid chromatography method which
      resolves 13 identified carotenoids and nine unknown carotenoids from human
      plasma. A Nucleosil C18 column and a Vydac C18 column in series are used with an
      isocratic solvent system of acetonitrile-methanol containing 50 mM acetate
      ammonium-dichloromethane-water (70:15:10:5, v/v/v/v) as mobile phase at a flow
      rate of 2 ml/min. The intra-day (4.5-8.3%) and inter-day (1.3-12.7%) coefficients
      of variation are suitable for routine clinical determinations.

PMID- 11236087
TI  - Methyl malondialdehyde as an internal standard for the determination of
      malondialdehyde.
AB  - Methyl malondialdehyde (Me-MDA) is suggested as an internal standard for the
      determination of the lipid peroxidation product, malondialdehyde (MDA). A
      procedure for synthesising the Me-MDA sodium salt is described in detail. The
      purity and identity of the synthesised Me-MDA have been confirmed using nuclear
      magnetic resonance and UV spectroscopy, and by micellar electrokinetic
      chromatography. The applicability of Me-MDA as an internal standard has been
      demonstrated for rat brain homogenate samples. These samples were purified solely
      through ultrafiltration. The preferred analytical technique was capillary zone
      electrophoresis (CZE) with UV detection at 267 nm. The limits of detection (3
      S/N) for the CZE separations of Me-MDA and MDA were 0.5 and 0.2 microM,
      respectively, and the total analysis time was approximately 10 min. Details of
      separations are also presented using high-performance liquid chromatography
      (HPLC) with UV detection at 245 nm, and gas chromatography, together with either
      electron capture or mass spectrometric detection. The GC separations require
      derivatisation of MDA and Me-MDA with pentafluorophenylhydrazine while the CZE
      and HPLC separations can be performed on the native molecules.

PMID- 11236086
TI  - Determination of monobromobimane derivatives of phenylmercapturic and
      benzylmercapturic acids in urine by high-performance liquid chromatography and
      fluorimetry.
AB  - A method was developed for the determination in human urine of S
      phenylmercapturic (PMA) and S-benzylmercapturic (BMA) acids, metabolites
      respectively of benzene and toluene. PMA and BMA were determined, after alkaline
      hydrolysis, to give respectively thiophenol and benzylmercaptan, and coupling of
      the thiol-containing compounds with monobromobimane (MB), by reversed-phase HPLC
      on a diphenyl-silica bonded cartridge (100 x 4.6 mm I.D., 5 microm particle size)
      with fluorimetric detection. Wavelengths for excitation and emission were 375 and
      480 nm, respectively. The recovery of PMA and BMA from spiked urines was >90% in
      the 10-500 microg/l range; the quantification limits were respectively 1 and 0.5
      microg/l; day-to-day precision at 42 microg/l was C.V. <7%. The suitability of
      the proposed procedure for the biological monitoring of exposure to low-level
      airborne concentrations of benzene and toluene, was evaluated by analyzing the
      urinary excretion of PMA and BMA in subjects exposed to different sources of
      aromatic hydrocarbons, namely occupationally-unexposed referents (non-smokers,
      n=15; moderate smokers, n=8; mean number of cigarettes smoked per-day=17 cig/day)
      and non-smoker workers occupationally exposed to toluene in maintenance
      operations of rotogravure machines (non-smokers, n=17). Among referents, non
      smokers showed values of PMA ranging from <1 to 4.6 microg/l and BMA from 1.0 to
      10.4 microg/l; in smokers, PMA values ranging from 1.2 to 6.7 microg/l and BMA
      from 9.3 to 39.9 microg/l, were observed. In occupationally exposed non-smoker
      subjects, BMA median excretion value (23.6 microg/l) was higher than in non
      smoker referents (3.5 microg/l) (P<0.001) and individual BMA values (y, microg/l)
      were associated and increased with airborne toluene concentration (x, mg/m3)
      according to the equation y=6.5+0.65x (r=0.69, P<0.01, n=17). The proposed
      analytical method appears to be a sensitive and specific tool for biological
      monitoring of low-level exposure to benzene and toluene mixtures in occupational
      and environmental toxicology laboratory.

PMID- 11236088
TI  - Determination of a new thymidine phosphorylase inhibitor, TPI, in dog and rat
      plasma by reversed-phase ion-pair high-performance liquid chromatography.
AB  - A high-performance liquid chromatographic method for the determination of a new
      thymidine phosphorylase inhibitor, TPI, in dog and rat plasma is described. TPI
      was isolated from biological samples by solid-phase extraction on Bond Elut PRS
      columns. Chromatographic separation was achieved on a C18 column using a mobile
      phase consisting of acetonitrile-10 mM acetate buffer (pH 4.3) including
      hexanesulfonate, with UV detection at 276 nm. This method has been validated
      across the range of 50-50000 ng/ml using a 0.1-ml plasma volume. The mean
      recoveries from spiked plasma were 93% for dog and 94% for rat, respectively. The
      accuracy, precision and specificity of the method were demonstrated to be
      acceptable, and it was applied to the toxicokinetic study of TPI in rats.

PMID- 11236089
TI  - Improved coupled column liquid chromatographic method for high-speed direct
      analysis of urinary trans,trans-muconic acid, as a biomarker of exposure to
      benzene.
AB  - A coupled column liquid chromatographic (LC-LC) method for high-speed analysis of
      the urinary ring-opened benzene metabolite, trans,trans-muconic acid (t,t-MA) is
      described. Efficient on-line clean-up and concentration of t,t-MA from urine
      samples was obtained using a 3 microm C18 column (50x4.6 mm I.D.) as the first
      column (C-1) and a 5 microm C18 semi-permeable surface (SPS) column (150x4.6 mm
      I.D.) as the second column (C-2). The mobile phases applied consisted,
      respectively, of methanol-0.05% trifluoroacetic acid (TFA) in water (7:93, v/v)
      on C-1, and of methanol-0.05% TFA in water (8:92, v/v) on C-2. A rinsing mobile
      phase of methanol-0.05% TFA in water (25:75, v/v) was used for cleaning C-1 in
      between analysis. Under these conditions t,t-MA eluted 11 min after injection.
      Using relatively non-specific UV detection at 264 nm, the selectivity of the
      assay was enhanced remarkably by the use of LC-LC allowing detection of t,t-MA at
      urinary levels as low as 50 ng/ml (S/N>9). The study indicated that t,t-MA
      analysis can be performed by this procedure in less than 20 min requiring only pH
      adjustment and filtration of the sample as pretreatment. Calibration plots of
      standard additions of t,t-MA to blank urine over a wide concentration range (50
      4000 ng/ml) showed excellent linearity (r>0.999). The method was validated using
      urine samples collected from rats exposed to low concentrations of benzene vapors
      (0.1 ppm for 6 h) and by repeating most of the analyses of real samples in the
      course of measurement sequences. Both the repeatability (n=6, levels 64 and 266
      ng/ml) and intra-laboratory reproducibility (n=6, levels 679 and 1486 ng/ml) were
      below 5%.

PMID- 11236090
TI  - Interaction between phosphofructokinase and aldolase from Saccharomyces
      cerevisiae studied by aqueous two-phase partitioning.
AB  - Phosphofructokinase (EC 2.7.1.11) and aldolase (EC 4.1.2.13) have been highly
      purified from Saccharomyces cerevisiae by improved protocols. Partitioning of the
      enzymes in aqueous polymer two-phase systems was used to detect complex
      formation. The partition of each enzyme was found to be affected by the presence
      of the other enzyme. AMP affected the partition of the individual enzymes as well
      as the mixture of the two. The activities of the respective enzymes were
      stimulated in the putative complex in an AMP-dependent manner. Two strictly
      conserved residues belonging to an acidic surface loop of class II aldolases, are
      a potential site for electrostatic interaction with the positively charged
      regions close to the active site in phosphofructokinase.

PMID- 11236091
TI  - Chromatographic identification of a biochemical alteration in the aqueous humour
      of megalophthalmic Black Moor goldfish.
AB  - PURPOSE: To observe if any biochemical abnormalities exist between the eye of
      megalophthalmic and non-megalophthalmic goldfish by high-performance liquid
      chromatography (HPLC). METHOD: Aqueous humour and sera from megalophthalmic and
      non-megalophthalmic goldfish were subjected to HPLC and monitored by photodiode
      array detection (Waters, MA, USA). RESULTS: An unusual accumulation of a compound
      with a UV absorption maximum at 290 nm was observed in the aqueous humour of
      megalophthalmic eye. This compound was also present in the sera of both normal
      goldfish and one of its megalophthalmic mutant. However, it was significantly
      elevated in the aqueous humour of the megalophthalmic eye only. This compound
      concentration was very high in the eye of small fish and its concentration
      increased only slightly with the expansion of the eye in larger fish.
      CONCLUSIONS: The presence of this compound in the serum and aqueous humour
      indicates a specific systemic metabolic variation in Black Moor goldfish not seen
      other animal species we had studied (humans, bovine, chick, rabbits and rats).
      The marked elevation of this compound in the megalophthalmic eye indicates a
      possible association of this compound with the metabolic variation accounting for
      the expansion of the eye in megalophthalmic goldfish.

PMID- 11236092
TI  - Rapid antibiotic drug monitoring: meropenem and ceftazidime determination in
      serum and bronchial secretions by high-performance liquid chromatography
      integrated sample preparation.
AB  - A sensitive and rapid HPLC assay for the determination of the beta-lactam
      antibiotics ceftazidime and meropenem in serum and bronchial secretions is
      described. HPLC-integrated sample preparation allows direct injection of serum
      samples without any pretreatment. Sputum samples need only a simple
      homogenisation and volume measurement but no liquefying reagents are necessary.
      The inline extraction technique is realized by automatically switching from the
      extraction column to the analytical column. After the matrix passed the
      extraction column, the retained analyte is quantitatively transferred to the
      analytical column where separation by isocratic HPLC is performed. Ceftazidime
      and meropenem are detected according to their absorption maxima at 258 and 296
      nm, respectively. The detection limit of both antibiotics is estimated to be
      better than 0.5 microg/ml in serum as well as in sputum samples. The described
      procedure allows determination of the antibiotics within 30-45 min, thereby
      facilitating drug monitoring in clinical routine.

PMID- 11236093
TI  - Determination of ethyl-p-hydroxybenzoate in sow pancreatic juice by reversed
      phase high-performance liquid chromatography.
AB  - We have developed a high-performance liquid chromatographic-UV-Vis-diode-array
      detection (HPLC-DAD) method for the determination of ethyl-p-hydroxybenzoate, a
      hydrolytic degradation product of the synthetic protease inhibitor, gabexate
      mesilate ethyl-p-(6-guanidinohexanoyloxy) benzoate methanesulfonate (GM) (FOY) in
      sow pancreatic juice. Methyl-p-hydroxybenzoate (I) was used as the internal
      standard. The pancreatic juice was deproteinised by acetonitrile and the analytes
      were chromatographed on a reversed-phase C18 LC column using the gradient elution
      method. The mobile phase consisted of a solution of 0.017 M orthophosphoric acid
      and another solution of acetonitrile-water (80:20, v/v). The wavelength of
      detection was 237 nm. The limit of quantification of the method was 0.20 microM
      at a 9:1 signal-to-noise ratio. The overall intra- and inter-day accuracy
      (relative error, RE) ranged from 14.2 to 8.3% and from 13.3 to 9.8, respectively.
      The overall intra- and inter-day precision (relative standard deviation, RSD)
      ranged from 7.6 to 2.62% and from 6.7 to 3.1%, respectively. The method proved to
      be sensitive, specific, accurate and precise and was successfully used to
      determine the ethyl-p-hydroxybenzoate (II) in sow pancreatic juice.

PMID- 11236094
TI  - Simple and rapid determination of nevirapine in human serum by reversed-phase
      high-performance liquid chromatography.
AB  - Nevirapine is an antiretroviral agent belonging to the class of non-nucleoside
      reverse transcriptase inhibitors. We describe a fast, simple isocratic reversed
      phase high-performance liquid chromatography method with a 30-mm long column for
      assaying nevirapine in human serum. After deproteinization of 200 microl serum
      samples with 50% trichloroacetic acid, the supernatant was injected into a
      reversed-phase C18 column, using 10 mM phosphate buffer (pH 5)-acetonitrile
      (82:18, v/v) as the mobile phase. Peak detection was performed at 240 nm.
      Nevirapine retention time was 2 min. The method was validated over 0.1-10
      microg/ml and the assay was linear over this concentration range (r2>0.998).
      Within- and between-day precisions were less than 5.4%. The lower limit of
      quantification was 0.1 microg/ml. Nevirapine in human serum samples was stable
      for 2 days at 20-25 degrees C, 15 days at 4 degrees C and 3 months at -20 degrees
      C.

PMID- 11236095
TI  - New sensitive assay of vancomycin in human plasma using high-performance liquid
      chromatography and electrochemical detection.
AB  - A method using reversed-phase high-performance liquid chromatography with
      electrochemical detection for the analysis of vancomycin in human plasma was
      developed. Chromatographic conditions included an octadecyl column, a mobile
      phase of acetonitrile-sodium phosphate buffer (pH 7) (12:88), a total run time of
      12 min, and coulometric electrochemical detection at +700 mV. Linear detector
      response was found in the range 5-100 microg ml(-1) after a 1:80 dilution or from
      0.5 to 50 microg ml(-1) after a 1:20 dilution of the samples. In both cases the
      correlation coefficient (r) of the calibration curve standard was better than
      0.995. Vancomycin determination was based on a denaturation of plasma proteins
      with methanol, then a dilution with mobile phase was performed. Recovery of
      vancomycin from plasma was 103.1+/-3.9%, and no interference from commonly used
      drugs or endogenous compounds was observed. A significant correlation was shown
      with the EMIT assay (r=0.92, P<0.001) using clinical samples from children. This
      HPLC technique is simple, sensitive, rapid, precise, selective and requires only
      100 microl of plasma for completion.

PMID- 11236096
TI  - Clinical adaptation of a high-performance liquid chromatographic method for the
      assay of pyridoxal 5'-phosphate in human plasma.
AB  - Vitamin B6, measured as pyridoxal 5'-phosphate (PLP), is a co-enzyme in the
      transsulfuration pathway of homocysteine metabolism. Since depletion of PLP has
      been suggested as an independent risk factor for coronary artery disease, PLP is
      frequently measured to guide patient care. By a change and utilization of an
      Aquasil C18 column and the addition of an acetonitrile clean-up gradient to the
      potassium phosphate, with sodium perchlorate and bisulfite buffer between samples
      we report the modification of a previously described method for analysis of PLP.
      The result is a more practical, efficient, reliable and robust method for daily
      clinical use. We also determined and report that it is critical to protect
      freshly prepared standard PLP samples from light exposure during assay
      preparation.

PMID- 11236097
TI  - Lung cancer in HIV-infected patients: a one-year experience.
AB  - The relative incidence and rate of lung cancer in HIV-infected patients compared
      with the general US population has been a source of controversy. We sought to
      establish these parameters in a cohort of 2616 HIV-infected patients. Tumour
      type, stage of disease, patient demographics and immune parameters including
      viral loads were ascertained. An annual rate of 191 cases/100,000 population was
      found, which is 3.01 times greater (95% confidence interval [CI]=1.3-7.0) when
      compared with the general US population and 7.4 times the rate in US males
      between ages 35 and 54 (95% CI=3.1-17.8). Three patients had CD4 counts greater
      than 200 cells/mm3 at diagnosis and 2 had undetectable viral loads. The mean age
      was 44 years and all had advanced disease and short survival. In conclusion, the
      incidence of primary lung cancer was increased in this cohort of HIV-infected
      patients and occurred over a wide range of immunosuppression and viral
      replication.

PMID- 11236098
TI  - Treatment-related empowerment: preliminary evaluation of a new measure in
      patients with advanced HIV disease.
AB  - This paper presents a novel method for assessing patients' perceptions of
      empowerment in the context of drug therapy, the Treatment-related Empowerment
      Scale (TES). The 10-item TES was specifically constructed to address components
      of communication, treatment choice, decision-making and satisfaction. Evaluation
      of the scale in a cross-sectional anonymous survey of 43 patients with advanced
      HIV infection revealed acceptable internal reliability (Cronbach's alpha=0.85)
      and evidence of both criterion and discriminant validity. Patients who perceived
      a high degree of treatment-related empowerment were less likely to view doctors
      as overly reliant on prescribing medicines and reported lower rates of
      intentional noncompliance. The TES has scope as a concise measure of patients'
      degree of control over the selection and use of drug therapy, and may be of
      particular value for current combination therapy regimens.

PMID- 11236099
TI  - Sexual behaviour, condom use and HIV risk situations in the general population of
      Quebec.
AB  - We conducted 3501 telephone interviews to determine the sexual and protective
      behaviours of the general population in Quebec. Among the 858 respondents who had
      had at least one occasional partner during the last 5 years, 25.4% had had at
      least one occasional partner who refused to use a condom. More women had had an
      occasional partner who had refused than men (29.8% vs 21.1%, P<0.001) and fewer
      women than men succeeded in negotiating condom use, but more of these women
      decided not to have sexual relations. The frequency of condom use during the last
      sexual relation changes if the partner is a regular cohabiting partner (12.5%), a
      regular non-co-habiting partner (42.2%) or an occasional partner (70.8%). Our
      study provides important information for the development of prevention programmes
      for the heterosexual population and demonstrates the importance of the type of
      relationship maintained by the partners on the sexual behaviours.

PMID- 11236100
TI  - The stability between two HIV-1 RNA measurements one year apart and the
      relationship with HIV subtype in rural Uganda.
AB  - We compared HIV-1 RNA levels using the nucleic acid sequenced based amplification
      (NASBA) test kit in 2 samples taken one year apart from participants infected
      with env subtype A or D in a population-based cohort in Uganda. Fifty
      participants were infected with subtype A and 70 with subtype D. HIV-1 RNA levels
      were significantly higher in subtype D unadjusted (P=0.001), and after adjusting
      for age, gender, and CD4 count (P<0.001). Eighty-six participants had HIV-1 RNA
      measurements in both years and 67 (78%) were within one log10 of their result a
      year before. There was no relationship between the difference in log viral load
      and proportion of CD4 change. Individuals infected with subtype D had a higher
      average increase in viral load and this was statistically significant if adjusted
      for baseline levels and CD4 count (P=0.015).

PMID- 11236101
TI  - Would you get your Gonorrhoea treated in the north of England?
AB  - The management outcome of gonorrhoea in the northern region of England was
      assessed and compared with the recently published national guidelines. An audit
      questionnaire was completed by all genitourinary medicine (GUM) clinics in the
      region. Information with regard to demographic data, microscopy, culture results,
      test of cure, antibiotic use and sensitivity and contact tracing were recorded. A
      total of 420 cases of gonorrhoea were diagnosed in 1998. The ratio of males to
      females with gonorrhoea was 2.1:1. Half were heterosexual males and one-third
      females. Direct microscopy was positive in 85% of heterosexual males but in less
      than one-third of females. Ciprofloxacin was the most commonly used antibiotic.
      One-third of the isolates were resistant or partially resistant to penicillin.
      Health advisors saw 85% of patients and 41-68% of 'potential' contacts were seen.
      The management of gonorrhoea in the northern region of England complies with the
      national guideline recommendations.

PMID- 11236102
TI  - A case of pneumocystis pneumonia after cessation of secondary prophylaxis.
AB  - Improvement in the immunological and virological profile of HIV-infected
      population during the era of highly active antiretroviral therapy (HAART), has
      allowed guidelines on discontinuation of Pneumocystis carinii pneumonia (PCP)
      prophylaxis to be published. A case of a 37-year-old homosexual man, who had
      sustained CD4 count over 200 cells/microl for 2 years while on secondary
      prophylaxis for PCP, who then developed PCP after cessation of prophylaxis, is
      presented. This case emphasizes the need for close monitoring of patients who
      discontinued secondary PCP prophylaxis with respiratory symptoms.

PMID- 11236103
TI  - Human immunodeficiency virus type 1 seroprevalence in central Uganda, 1998.

PMID- 11236104
TI  - Provision of sexual health services in young offender institutions: is there
      gender inequality?

PMID- 11236105
TI  - Impact of adequate medical manpower in genitourinary medicine service delivery.

PMID- 11236106
TI  - Continuing medical ignorance: modern myths in the management of genital warts.
AB  - Genital warts are the most common sexually transmitted disease (STD) in
      industrialized countries. Since they also often respond poorly to current
      treatments, they account for substantial morbidity. Human papillomavirus (HPV)
      typing methods have shown that HPV 6 and 11, the most common types found in
      genital warts, are not found in cancer of the cervix. These types, however, do
      cause minor degrees of cervical dysplasia which also results in morbidity both
      through fear and through over-treatment. The sexual nature of transmission of
      genital warts has been known from ancient times; there is also good evidence of
      vertical transmission and transmission through non-genital contact. Barrier
      contractive methods do not completely prevent transmission of genital warts and
      may give little worthwhile protection. These facts, together with the established
      persistence of HPV contribute to the associated psychological morbidity. There
      are a number of treatments for genital (and other) warts. This attests to the
      fact that no one of these is clearly superior to the others. Until better
      treatments are developed much of the management of this condition must consist of
      using such treatments that are available to maximize efficacy while trying to
      reduce unnecessary costs, inconvenience and potential injury and sustaining
      morale through what may be a long and demoralizing course.

PMID- 11236107
TI  - Plasma cell balanitis of Zoon: response to Trimovate cream.
AB  - Our objective was to evaluate the response to Trimovate cream in patients with
      Zoon's balanitis. Patients attending the penile dermatosis clinic between October
      1996 and October 1999 with the clinical and histological features diagnostic of
      Zoon's balanitis were included in this study. They were treated with Trimovate
      cream for a varying length of time according to clinical response, having
      declined circumcision as first-line treatment. All cases had photographs taken
      before and after treatment. Ten cases of histologically-confirmed Zoon's
      balanitis were treated. Clinical resolution was observed in all cases, all of
      whom remain on long-term follow-up. In conclusion, topical Trimovate cream is an
      effective treatment for Zoon's balanitis.

PMID- 11236108
TI  - Varicella zoster virus-associated neurological disease in HIV-infected patients.
AB  - Varicella zoster virus (VZV) is an uncommon but well recognized cause of
      neurological disease in HIV-infected patients. Analysis of cerebrospinal fluid
      (CSF) using the polymerase chain reaction (PCR) in HIV-infected patients
      presenting with neurological disease has increasingly allowed diagnosis of VZV
      associated pathology. We report clinical, radiological and virological data from
      15 consecutive patients with VZV-associated neurological disease. Clinical
      presentation was varied, including meningo-encephalitis in 9 and isolated cranial
      nerve palsies in 6. VZV deoxyribonucleic acid (DNA) was detected by PCR in CSF of
      11/15; pleocytosis was present in only 6/15, raised protein in 11/15. Magnetic
      resonance imaging (MRI) appearances were focal signal abnormalities in 8,
      meningeal enhancement in 2 and normal in 2. With specific anti-VZV therapy 10
      patients recovered fully. The predictive value of PCR on CSF for diagnosis of VZV
      associated neurological disease should take into account the patient's clinical
      presentation, concurrent infections and response to anti-VZV therapy.

PMID- 11236109
TI  - Switch of protease inhibitor-containing HAART in routine clinical practice: a
      four-year prospective observational study.
AB  - An evaluation was made of the frequency of outcomes, the features, and one-year
      outcomes of the substitution, carried out because of failure or toxicity, of
      protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART).
      Nine hundred and seventy-two HIV-infected patients were prospectively followed up
      since 1996, with the condition that they had a minimum 80% adherence to
      prescribed regimens. Four hundred and fifty-two changes occurred in 397 of the
      876 evaluable patients (45.3%). Virological and/or immunological failure was of
      concern in 245 cases (54.2%). Interest in saquinavir had the greatest incidence
      and earliest occurrence (although the subsequent switch had a significantly
      better outcome than that of patients failing with other PIs); nelfinavir
      benefited from a shorter time to change and a worse long-term outcome (probably
      attributable to its predominant use in indinavir- and ritonavir-experienced
      patients); while indinavir showed the lowest overall frequency of substitution.
      Intolerance occurred in the remaining 207 cases (45.8%); with saquinavir being
      better tolerated than other PIs. A favourable outcome was obtained more
      frequently when poor tolerability was of concern, compared with therapeutic
      failure (P<0.008), while no significant differences were found according to prior
      antiretroviral experience and the subsequently selected HAART regimen. The
      overall one-year outcome per single substituted compound proved significantly
      better for patients who stopped using saquinavir and ritonavir, by contrast with
      those who stopped using indinavir and nelfinavir (P<0.0008). A significantly
      shorter mean time to substitution was recognized for nelfinavir and saquinavir
      than with ritonavir and indinavir (P<0.0001). When analysing the subset of
      patients experiencing HAART failure, a highly significant reverse relationship
      was demonstrated between mean time to failure, and rate of subsequent response to
      a modified antiretroviral regimen (P<0.0001). When considering the different
      patterns of efficacy, durability, resistance induction, expected adherence, and
      safety of each antiretroviral drug, initial and subsequent therapeutic choices
      should be carefully balanced against expected benefits and risks.

PMID- 11236110
TI  - Antimicrobial susceptibilities and plasmid patterns of Neisseria gonorrhoeae in
      Benin.
AB  - This study describes antimicrobial susceptibility patterns of Neisseria
      gonorrhoeae isolates obtained from female sex workers in Cotonou, Benin. All
      isolates were susceptible to spectinomycin, ceftriaxone and ciprofloxacin, and
      susceptible to moderately susceptible to kanamycin; 9.8% of isolates were
      resistant to thiamphenicol; 9%, 87.5% and 3.5% were susceptible, moderately
      susceptible, resistant to trimethoprim-sulfamethoxazole, respectively; 94.4% and
      99.3% were resistant to penicillin and tetracycline, respectively. All isolates
      with a minimal inhibitory concentration of tetracycline of >8 mg/l carried the
      'American type' tetM plasmid; 94% and 6% of penicillinase-producing isolates
      possessed a 3.2 MDa and a 4.4MDa beta-lactamase plasmid, respectively.
      Surveillance of antimicrobial susceptibility of N. gonorrhoeae isolates to
      currently used drugs in Africa should become part of sexually transmitted
      diseases (STDs) control programmes.

PMID- 11236111
TI  - Participants in HIV clinical trials in Europe.
AB  - In recent years an increasing number of antiretrovirals have become available. In
      order to define the optimal treatment regimens an increasing number of clinical
      trials are needed. Our objective was to study the profile of participants in HIV
      clinical trials in Europe and learn from their experience and views. Between
      August 1996 and September 1997, self-administered anonymous questionnaires were
      distributed to people with HIV infection at inpatient and outpatient clinics in
      11 European countries. One thousand three hundred and sixty-six people completed
      the questionnaire (50% response rate). Four hundred and twenty (31%) of the
      respondents reported that they had previously participated in at least one HIV
      clinical trial. The percentage of people who had taken part in a clinical trial
      varied widely between the different centres, from 12% in Athens to 61% in Antwerp
      and Brussels. A significantly higher participation rate was observed in the
      northern and central part of Europe compared with the south (respectively 40% vs
      18%) and also among people with a higher income. Most people (92%) stated that
      they were 'well' or 'very well' informed prior to enrolment in the trial.
      However, 4% reported that they had not given written approval and 22% felt that
      they were pushed into participating. Only 21% stated that they were informed
      about the outcome of the study on its completion. The most important reason for
      non-participation (37% of the non-participants) was because a clinical trial had
      never been proposed. In conclusion, a majority of people with HIV infection in
      European HIV treatment reference centres were willing to participate in clinical
      trials. HIV clinical trials in Europe should adhere more strictly to universal
      ethical standards.

PMID- 11236113
TI  - A randomised controlled trial of antibiotic prophylaxis in elective caesarean
      delivery.
AB  - OBJECTIVE: To determine whether prophylactic antibiotic administration using
      cefoxitin at the time of elective caesarean section significantly reduces
      infectious morbidity. SETTING: A tertiary teaching hospital in a large urban city
      in South Africa. PARTICIPANTS: Women undergoing elective caesarean section.
      DESIGN: A prospective, double-blind randomised placebo-controlled trial. METHODS:
      Four hundred and eighty women undergoing elective caesarean section had cefoxitin
      or placebo administration after umbilical cord clamping. Postpartum complications
      including febrile morbidity, wound infection, endometritis, urinary tract
      infection, pneumonia and transient postpartum fever were recorded, as were the
      duration of hospital stay and the need for therapeutic antibiotics. RESULTS:
      Wound infection was the most common complication occurring in 13.3% and 12.5% of
      women in the placebo and cefoxitin groups, respectively. Prophylactic antibiotics
      did not decrease febrile morbidity, wound infection, endometritis, urinary tract
      infection and pneumonia. Women who received cefoxitin stayed on average a day
      less in hospital than those who received placebo (6.9 vs 7.8 days, risk
      difference 0.94 CI 1.57 - 0.31 days). Eleven women (4.6%) in the placebo group
      and eight (3.4%) in the cefoxitin group had microbiological evidence of wound
      infection. Staphylococcus aureus was the most common pathogen (43%) isolated.
      Similar proportions in both groups (6.3% placebo and 5.1% cefoxitin) required a
      course of therapeutic antibiotics. CONCLUSION: Antibiotic prophylaxis with
      cefoxitin in elective caesarean section did not reduce post-operative infectious
      morbidity in this double-blind randomised placebo controlled trial.

PMID- 11236112
TI  - Effectiveness and safety of the oxytocin antagonist atosiban versus beta
      adrenergic agonists in the treatment of preterm labour. The Worldwide Atosiban
      versus Beta-agonists Study Group.
AB  - OBJECTIVE: To compare the effectiveness and safety of the oxytocin antagonist
      atosiban with conventional beta-adrenergic agonist (beta-agonist) therapy in the
      treatment of preterm labour. DESIGN: Three multinational, multicentre, double
      blind, randomised, controlled trials. Setting Hospitals in Australia, Canada,
      Czech Republic, Denmark, France, Israel, Sweden, and the UK. POPULATION: Women
      diagnosed with preterm labour at 23-33 completed weeks of gestation. METHODS:
      Seven hundred and forty-two women were randomised; 733 received atosiban (n =
      363; intravenous (iv) bolus dose of 6.75 mg, then 300 microg/minute iv. for 3h
      and 100 microg/min iv thereafter) or beta-agonist (n = 379; ritodrine, salbutamol
      or terbutaline iv; dose titrated) for at least 18h and up to 48 hours. Uterine
      contraction rate, cervical dilatation and effacement were used to assess
      progression of labour. An all patients treated analysis, using the Cochran-Mantel
      Haenszel test, was performed. MAIN OUTCOME MEASURES: Tocolytic effectiveness was
      assessed in terms of the number of women undelivered after 48 hours and seven
      days. Safety was assessed in terms of maternal side effects and neonatal
      morbidity. RESULTS: There were no significant differences between atosiban and
      beta-agonists in delaying delivery for 48h (88.1% vs 88.9%; P = 0.99) or seven
      days (79.7% versus 77.6%; P = 0.28). Tocolytic effectiveness was also similar in
      terms of mean [SD] gestational age at delivery (35.8 [3.9] weeks vs 35.5 [4.1]
      weeks) and mean [SD] birthweight (2,491 [813] g versus 2,461 [831] g). Maternal
      side effects, particularly cardiovascular adverse events (8.3% vs 81.2%, P <
      0.001), were reported more frequently in women given beta-agonists, resulting in
      more treatment discontinuations due to side effects (1.1% vs 15.4%, P = 0.0001).
      No statistical differences in neonatal/infant outcomes were observed with either
      study medication. CONCLUSIONS: In the largest study of tocolytic therapy to date,
      atosiban was comparable in clinical effectiveness to conventional beta-agonist
      therapy, but was associated with fewer maternal cardiovascular side effects. We
      conclude that atosiban has clinical advantages over current tocolytic therapy.

PMID- 11236114
TI  - Systematic review of economic aspects of alternative modes of delivery.
AB  - OBJECTIVE: To carry out a systematic review of the literature relating to
      economic aspects of alternative modes of delivery. METHODS: A comprehensive
      literature search of the years 1990-1999 was conducted of electronic and non
      electronic sources using a tested search strategy. Papers considered to contain
      useful cost or resource use data were read in full and classified according to
      their relevance to the review and their methodological quality. Relevant cost and
      resource use data were converted to pound sterling and inflated to 1998-1999
      price levels. RESULTS: The literature search resulted in 975 papers, 49 of which
      met criteria for the review. Thirty-two papers were from the USA where the
      organisation, structure and costs of health care are significantly different from
      that of other industrialised countries. The aggregate costs of different modes of
      delivery reported in these American studies were between four and five times
      higher than costs reported in other studies. The majority of included studies
      were of poor quality. Data from the better quality studies demonstrated that
      caesarean section costs a health service substantially more than other modes of
      delivery. The range of costs of an uncomplicated vaginal delivery were 629 pound
      sterling  -  1,298 pound sterling compared with1,238 pound sterling  - 3,551
      pound sterling  for a caesarean section. However, papers have so far only
      considered short term health service costs. CONCLUSIONS: Research is required to
      estimate the cost and resource use attributable to alternative modes of delivery.
      Future research should investigate the long term health service costs and the
      costs that arise outside the health service which are likely to vary according to
      mode of delivery.

PMID- 11236116
TI  - Oxytocics reverse the tocolytic effect of glyceryl trinitrate on the human
      uterus.
AB  - OBJECTIVES: To investigate the effect of glyceryl trinitrate on isolated human
      pregnant uterine strips and whether the uterine relaxation induced by glyceryl
      trinitrate could be reversed by oxytocics used in current clinical practice.
      DESIGN: In vitro pharmacological study. SETTING: Department of Obstetrics &
      Gynaecology, National University of Singapore, National University Hospital.
      PARTICIPANTS: Eighteen women who delivered by caesarean section at term. METHODS:
      Myometrial strips were preloaded with an initial tension of 1.5g in organ baths
      containing Krebs-Henseleit solution which was aerated with oxygen in 5% carbon
      dioxide and maintained at 37 degrees C, pH 7.4. The effect of glyceryl trinitrate
      was studied in strips displaying regular spontaneous contractions. The ability of
      oxytocin, ergometrine or prostaglandin F2alpha to stimulate uterine contractions
      was assessed in strips where uterine activity was significantly inhibited by
      glyceryl trinitrate. RESULTS: Glyceryl trinitrate reduced the amplitude and
      frequency of spontaneous uterine contractions in a concentration-dependent
      manner, although the sensitivity of the myometrial strips varied considerably
      from one specimen to another. The concentration of glyceryl trinitrate producing
      complete inhibition of myometrial contractions ranged from 44-705 microM. In the
      presence of glyceryl trinitrate which markedly depressed spontaneous
      contractions, oxytocin (20 mU/mL), ergometrine (6.15 microM) and prostaglandin
      F2alpha (6.15 microM) were capable of reversing the uterine activity to either
      higher than or the untreated level of contractility. CONCLUSIONS: This study
      demonstrates that glyceryl trinitrate is a potent uterine relaxant in vitro and
      that the tocolytic effect could be reversed with ease by oxytocics.

PMID- 11236115
TI  - Expectant management of early pregnancies of unknown location: a prospective
      evaluation of methods to predict spontaneous resolution of pregnancy.
AB  - OBJECTIVE: To assess prospectively the ability of two multiparameter diagnostic
      models and their individual components to predict the outcome of early
      pregnancies which could not be identified on transvaginal ultrasound scan.
      DESIGN: Prospective observational study. SETTING: Dedicated early pregnancy unit
      in an inner city teaching hospital. POPULATION: Women with a positive urine
      pregnancy test and clinical suspicion of early pregnancy complications. METHODS:
      A full medical history, clinical examination and transvaginal ultrasound scan
      were carried out at the initial visit. When the location of the pregnancy could
      not be ascertained by ultrasound, serum beta-human chorionic gonadotrophin (beta
      hCG) and progesterone levels were measured. All women were managed expectantly
      until either a normal pregnancy was visualised on scan; the pregnancy resolved
      spontaneously or intervention was required due to a worsening of clinical
      symptoms or non-declining beta-hCG levels. MAIN OUTCOME MEASURES: Spontaneous
      resolution of pregnancy (i.e. cessation of symptoms and decline in serum beta-hCG
      level to < 20 iu/L) without need for any active intervention. RESULTS: Of the 104
      women recruited, 72 (69%) pregnancies resolved spontaneously. Both multiparameter
      diagnostic models identified resolving pregnancies with positive predictive
      values > or = 95%. Their performances were not significantly better compared with
      individual progesterone levels which achieved a positive predictive value of 97%
      using a cutoff level of 20 nmol/L. CONCLUSION: Serum progesterone measurement
      alone is as accurate as more complex diagnostic models for the prediction of
      successful expectant management in pregnancies of unknown location.

PMID- 11236117
TI  - In vivo controlled release of PGE2 from a vaginal insert (0.8 mm, 10 mg) during
      induction of labour.
AB  - OBJECTIVE: To measure the release rate of prostaglandin E2 (PGE2) in vivo from a
      controlled-release vaginal insert used for cervical ripening and induction of
      labour at term in women with intact membranes or pre-labour rupture of membranes
      (PROM). DESIGN: Open-label, single centre study. POPULATION: Women at term (> or
      = 37 gestational weeks) with unripe cervices (Bishop score < or = 6) scheduled
      for labour induction for mainly medical reasons. METHODS: sixty-eight women (47
      with intact membranes and 21 with PROM) had the PGE2 vaginal insert placed in the
      posterior fornix of the vagina. Each insert was removed from the women at a
      predetermined time interval between 0.5 h and 24 h, or earlier if labour was
      induced, fetal distress was detected or maternal complications occurred. After
      removal, the vaginal insert was frozen and stored for subsequent assay of
      residual PGE2. Blood samples were collected immediately before insertion and at 4
      hour intervals until removal of the vaginal insert to determine plasma
      concentrations of PGE2 and the major PGE metabolite, 15-Keto-13, 14-dihydro
      PGF2alpha (PGEm). Vaginal pH was measured immediately before insertion and
      directly after removal of the vaginal insert. Bishop score was assessed before
      induction, after 8 h, 12 h and immediately after removal of the vaginal insert.
      RESULTS: There was a positive linear relationship between the amount of PGE2
      released from the insert and the duration of treatment in women with intact
      membranes (rp = 0.95, P = 0.0001), with a calculated PGE2 release rate of 0.52 +/
      0.33 mg/h over 24 h. The PGE2 release rate in women with PROM was not linear.
      The PGE2 release rate was dependent on vaginal pH, with a faster release rate at
      higher vaginal pH. Forty-seven women (69.1%) had the insert removed due to the
      successful induction of labour and consequently discontinued study treatment
      before their allocated time period. At vaginal delivery, the released amount of
      PGE2 at onset of labour was 4.0 +/- 3.0 mg and 2.4 +/- 2.1 mg for nulliparous
      women with PROM and intact membranes, respectively (P = 0.1). In multiparous
      women, the equivalent mean released amount was 3.2 +/- 2.6 mg and 1.9 +/- 1.4 mg,
      respectively (P = 0.14). In women with intact membranes, the mean plasma
      concentrations of PGE2 and PGEm after treatment were not statistically different
      to those women with PROM (P = 0.27 and 0.64, respectively). In women who were
      delivered vaginally, the median induction to delivery time interval was 17.0 h
      (range 4-42) in nulliparous women and 8.7 h (range 5-19) in multiparous women (P
      = 0.003). Ten (14.7%) women, who were all nulliparous, were delivered by
      caesarean section. CONCLUSIONS: In women with intact membranes, the PGE2 release
      rate was linear over 24 hours. There was a positive linear relationship between
      vaginal pH and PGE2 release rate. The metabolite analysis revealed no evidence of
      dose dumping neither in women with intact membranes or in women with PROM.

PMID- 11236118
TI  - The fetal cardiac isovolumetric contraction time in normal pregnancy and in
      pregnancy with placental vascular disease: the first clinical report using a new
      ultrasound technique.
AB  - OBJECTIVE: To study the fetal cardiac isovolumetric contraction time in normal
      and complicated pregnancies with placental vascular disease using a newly
      developed digital Doppler cardiography system. DESIGN: A preliminary case-control
      study. SETTING: Tertiary referral hospital. SAMPLE: One hundred and sixteen
      normal fetuses (20 to 40 weeks) and 55 complicated pregnancies with placental
      vascular disease as documented by a high systolic: diastolic ratio in the
      umbilical artery Doppler flow study. METHOD: A digital Doppler cardiography
      system with a high sampling rate (4,000 Hz) was used to detect the fetal cardiac
      valvular movements. The isovolumetric contraction time was measured as the
      interval between the mitral valve closing and the aortic valve opening with a
      built-in scale device. RESULTS: In normal pregnancy the isovolumetric contraction
      time remained remarkably constant with gestation and fetal heart rate. Comparison
      between clinical outcome and the isovolumetric contraction time of the
      complicated fetuses who were born within a week after the last determination of
      the isovolumetric contraction time revealed a strong correlation between
      prolonged isovolumetric contraction time duration and abnormalities in the
      perinatal course (non-reactive fetal heart rate pattern, low pulsatility index in
      the fetal middle cerebral artery Doppler flow and low birthweight infant).
      CONCLUSIONS: The isovolumetric contraction time is constant with gestation and
      fetal heart rate in normal pregnancy. In the presence of placental vascular
      disease a prolonged fetal isovolumetric contraction time predicts adverse
      outcome.

PMID- 11236119
TI  - Female genital mutilation: analysis of the first twelve months of a Southeast
      London specialist clinic.
AB  - OBJECTIVES: To analyse the sources and reasons for referral of women who have
      undergone genital mutilation to a recently established specialist clinic, and to
      determine the consequences of the genital mutilation procedure. DESIGN:
      Retrospective descriptive case series. SETTING: The maternity units of Guy's and
      St. Thomas's Hospital, London. POPULATION: One hundred and sixteen women
      attending the clinic over a one-year period. MAIN OUTCOME MEASURES: (1) sources
      and reasons for referral to the specialist clinic; (2) characteristics of the
      women attending the clinic; (3) acute and chronic complications of the genital
      mutilation procedure; (4) attitudes towards female genital mutilation. RESULTS:
      Complete case records were available for 108 women. Of the 86 women who could
      remember the procedure, 78% were performed by a medically unqualified person,
      usually at home (71%), at a median age of seven years. Acute and chronic
      complications were each present in 86% of women with Type III genital mutilation.
      Most women (82%) were referred by their midwife because they were pregnant, of
      whom 48% were primigravid. Eighteen non-pregnant women also attended the clinic
      to request either defibulation or for advice. None of the 89 pregnant women
      requested re-infibulation after delivery, but almost 6% were seriously
      considering having their daughter undergo genital mutilation outside the United
      Kingdom. In addition, fewer than 10% of the women refused to continue the
      tradition of female genital mutilation. CONCLUSIONS: During its first year, the
      recently established African Well Woman Clinic has provided specialist care for
      116 women with genital mutilation. Such women may attend with a variety of common
      medical or psychiatric conditions and often do not volunteer that they have
      undergone the procedure. Doctors and midwives in particular, should enquire
      specifically about genital mutilation when caring for women from high risk
      countries, and offer the services of specialist clinics for female genital
      mutilation.

PMID- 11236120
TI  - A randomised trial comparing single dose systemic methotrexate and laparoscopic
      surgery for the treatment of unruptured tubal pregnancy.
AB  - OBJECTIVE: To compare single dose systemic methotrexate (50 mg/m2) with
      laparoscopic surgery for the treatment of unruptured tubal pregnancy. DESIGN: An
      open, pragmatic, prospective randomised trial. SETTING: Departments of obstetrics
      and gynaecology at three hospitals in Auckland, New Zealand. PARTICIPANTS:
      Clinically stable women with an unruptured tubal pregnancy diagnosed by
      transvaginal ultrasound and quantitative serum beta-hCG measurement. Inclusion
      criteria included a serum beta-hCG concentration < 5,000 IU/L, and a tubal
      pregnancy of < 3.5 cm diameter. MAIN OUTCOME MEASURES: Treatment success,
      physical and psychological functioning, side effects, and subsequent ipsilateral
      tubal patency. RESULTS: Two hundred and eighteen women with ectopic pregnancies
      were seen at the three hospitals. 79 women (36% eligibility rate) were eligible
      for trial entry and 62 women (78% recruitment rate) were recruited. Twenty-six of
      the 28 women (93%) randomised to laparoscopic surgery required no further
      treatment, compared with 22 of the 34 women (65%) randomised to methotrexate (95%
      CI of difference in success rate 10 - 47%; P < 0.01). Two women (7%) in the
      laparoscopic surgery group had persistent trophoblast. Nine women (26%) in the
      methotrexate group required more than one dose of methotrexate and five women
      (15%) underwent laparoscopy during follow up. In the laparoscopy group three
      women (11%) had negative laparoscopies and two women (7%) had were found to have
      a ruptured fallopian tube at the time of surgery. Women treated with methotrexate
      had significantly better objective physical functioning scores but there were no
      differences in any other psychological outcomes. Women treated with methotrexate
      experienced greater and more prolonged vaginal bleeding. The likelihood of
      methotrexate treatment failure was greater at higher serum beta-hCG
      concentrations. Ipsilateral tubal patency rates were similar in each group.
      CONCLUSION: This trial shows that in the treatment of tubal pregnancy single dose
      systemic methotrexate is a less effective treatment than laparoscopic
      salpingotomy. It is well tolerated, but should only be offered as an alternative
      to surgery to women who have mild symptoms and present at low serum beta-hCG
      concentrations. In our population this likely to be no more than a quarter of
      women presenting with a tubal pregnancy.

PMID- 11236121
TI  - An economic evaluation of single dose systemic methotrexate and laparoscopic
      surgery for the treatment of unruptured ectopic pregnancy.
AB  - OBJECTIVE: To compare the direct and indirect costs of single dose systemic
      methotrexate with laparoscopic surgery for the treatment of unruptured ectopic
      pregnancy. DESIGN: A cost minimisation study undertaken alongside a randomised
      trial. SETTING: Departments of Obstetrics and Gynaecology in three hospitals in
      Auckland, New Zealand. PARTICIPANTS: Sixty-two women with an ectopic pregnancy
      randomised to treatment with either a single dose of methotrexate (50 mg/m2) or
      laparoscopic surgery. MAIN OUTCOME MEASURES: Direct and indirect costs based on
      the results of the randomised trial. RESULTS: Direct costs per case were
      significantly lower in the methotrexate group (mean $NZ 1,470) than in the
      laparoscopy group (mean $NZ 3,083) with a mean difference of $NZ 1,613 (95% CI
      $NZ 1,166 - $NZ 2,061). These significant differences existed under a wide range
      of alternative assumptions about unit costs. The difference in direct costs in
      favour of methotrexate was greatest for women presenting with low pretreatment
      serum beta-hCG concentrations. Mean indirect costs were also significantly lower
      in the methotrexate group (mean $NZ 1,141) than in the laparoscopy group (mean
      $NZ 1899) with a mean difference of $NZ 758 (95% CI $NZ 277 - $NZ 1,240). For
      women presenting with pretreatment serum beta-hCG concentrations of over 1,500
      IU/ L this difference in indirect costs is lost due to the prolonged follow up
      required and a higher rate of surgical intervention in women receiving
      methotrexate. CONCLUSION: This economic evaluation shows that treating suitable
      women with an ectopic pregnancy using systemic methotrexate therapy results in a
      significant reduction in direct costs. The indirect costs borne by the woman and
      her carers are only likely to be reduced in women with pretreatment serum beta
      hCG concentrations under 1,500 IU/L.

PMID- 11236122
TI  - The treatment of incomplete miscarriage with oral misoprostol.
AB  - In a retrospective study of 112 women, the effectiveness of three sequential oral
      doses of misoprostol was evaluated for the treatment of incomplete miscarriage.
      We report our experience with this regimen, which achieved a complete miscarriage
      rate of 85%. Surgical intervention was required in 17 women (15%). The regimen
      appears to be effective in terms of a high rate of complete miscarriage, and it
      is safe.

PMID- 11236123
TI  - Aneuploidy screening in direct chorionic villus samples by fluorescence in situ
      hybridisation: the use of commercial probes in a clinical setting.
AB  - The results of screening for the common aneuploidies involving chromosomes 13,
      18, 21, X and Y by florescent in-situ hybridisation (FISH) in direct preparations
      from 100 chorionic villus samples from pregnancies between 10 and 20 weeks'
      gestation are reported. Samples prepared using routine methods and analysed with
      commercially available probes, accurately detected 12 cases of fetal aneuploidy,
      all referred because of developmental abnormality. Three of the four cases where
      chromosome abnormality was detected in cultured villi but not by the direct
      fluorescence in situ hybridisation (FISH) assay, were due to confined placental
      mosaicism. No chromosomal anomalies were found in the 20 low risk cases where the
      referral reason was a familial single gene disorder. We conclude that the FISH
      assay with commercial probes may act as an accurate and less labour intensive
      alternative to direct chromosome analysis of chorionic villus samples. In
      cytogenetically low risk cases its use can obtain a result within the time needed
      for DNA analysis and avoid the need to set up cultures.

PMID- 11236124
TI  - Prenatal hypoxic ischaemic-encephalopathy leading to microcephaly in a sickle
      cell pregnancy with recovery from a 'terminal CTG'.

PMID- 11236125
TI  - Acute fatty liver of pregnancy at 23 weeks of gestation.

PMID- 11236126
TI  - Oesophageal and duodenal atresia suspected at the 12 week booking scan.

PMID- 11236127
TI  - Fasciitis: a rare complication of Burch colposuspension.

PMID- 11236128
TI  - Premature ovarian failure due to an unbalanced translocation on the X chromosome.

PMID- 11236129
TI  - Careful screening to target interventions to prevent sudden cardiac death.
AB  - 1. Cardiac death is due not only to coronary artery disease, but also to left
      ventricular (LV) abnormalities (fibrosis, dysfunction) and arrhythmogenic
      triggers, such as autonomic imbalance. 2. Nitric oxide deficiency could be a key
      mediator leading not only to coronary atherosclerosis, but also to LV
      abnormalities and autonomic imbalance. 3. It may be possible to screen for the
      above abnormalities (e.g. echocardiography and brain natriuretic peptide levels
      for LV abnormalities, 24 h tapes for autonomic imbalance and QT interval
      analysis). 4. Once individuals are identified as being at high risk, a range of
      interventions is possible (e.g. intensive statin therapy or angiotensin
      converting enzyme inhibitors if LV abnormalities or autonomic imbalance are
      found).

PMID- 11236130
TI  - From 'captive' agonism to insurmountable antagonism: demonstrating the power of
      analytical pharmacology.
AB  - 1. Mathematical modelling is useful in pharmacology, allowing the investigator to
      obtain insights into the biological processes under study that may not always be
      intuitively obvious. Examples are presented in this review using the pharmacology
      of the muscarinic acetylcholine receptor (mAChR) agonist xanomeline. 2.
      Xanomeline possesses a novel mode of action that involves persistent binding to
      the M1 mAChR, yielding a fraction of agonist in the receptor compartment that
      continually activates the receptor, despite extensive washout, as assessed in
      functional assays measuring the cumulative production of M1 mAChR-mediated L-[3H]
      citrulline. This persistent effect was reversed by the antagonist atropine, but
      re-established upon the removal of atropine. Thus, xanomeline may represent the
      first 'captive' agonist of the mAChR. 3. Atropine was equally potent at reversing
      the effect of persistently bound xanomeline and preventing the effect of added
      xanomeline. Application of standard quantitative equilibrium models of agonist
      antagonist interaction to these data suggested that the interaction between
      xanomeline and atropine satisfied the criteria of competitivity in each case. 4.
      Subsequent real-time assays of M1 mAChR-mediated intracellular calcium
      mobilization found that atropine inhibited the effects of xanomeline in an
      insurmountable manner. 5. The discrepancy between the modes of antagonism in the
      various functional assays could be reconciled in a dynamic receptor model of
      antagonism within a transient response system and subsequent Monte Carlo
      simulations allowed for the development of an optimized analytical procedure to
      quantify antagonist potency under such conditions of response fade. 6. These
      types of studies exemplify the diagnostic and integrative features of analytical
      pharmacology.

PMID- 11236131
TI  - Immune-derived opioids and peripheral antinociception.
AB  - 1. Recent findings have suggested a significant involvement of the immune system
      in the control of pain. Immune cells contain opioid peptides that are released
      within inflamed tissue and act at opioid receptors on peripheral sensory nerve
      endings. It is also apparent that different types of lymphocytes contain beta
      endorphin, memory T cells containing more beta-endorphin than naive cells. 2.
      These findings highlight an integral link between immune cell migration and
      inflammatory pain. The present review highlights immune system involvement in the
      site-directed control of inflammatory pain. 3. Full-length mRNA transcripts for
      opioid precursor proteins are expressed in immune cells. Increased expression of
      pro-opiomelanocortin mRNA and beta-endorphin has been demonstrated in stimulated
      lymphocytes and lymphocytes from animals with inflammation. 4. Cytokines and
      corticotropin-releasing factor (CRF) release opioids from immune cells. Potent
      peripheral analgesia due to direct injection of CRF can be blocked by antagonists
      to CRF, antibodies to opioid peptides, antisense to CRF and opioid receptor
      specific antagonists. The release of opioid peptides from lymphocytes is calcium
      dependent and opioid receptor specific. Furthermore, endogenous sources of opioid
      peptides produce potent analgesia when implanted into the spinal cord. 5.
      Activated immune cells migrate directly to inflamed tissue using cell adhesion
      molecules to adhere to the epithelial surface of the vasculature in inflamed
      tissue. Lymphocytes that have been activated can express opioid peptides. Memory
      type T cells that contain opioid peptides are present within inflamed tissue;
      naive cells are not present in inflamed tissue and do not contain opioid
      peptides. Inhibiting the migration of memory type T cells into inflamed tissue by
      blocking selectins results in reduced numbers of beta-endorphin-containing cells,
      a reduced quantity of beta-endorphin in inflamed paws and reduced stress- and CRF
      induced peripheral analgesia. 6. Immunosuppression is associated with increased
      pain in patients. Moreover, immunosuppression results in decreased lymphocyte
      numbers as well as decreased analgesia in animal models.

PMID- 11236132
TI  - Role of human airway smooth muscle in altered extracellular matrix production in
      asthma.
AB  - 1. The underlying abnormality in asthma is not fully understood; however,
      inflammation, airway remodelling and bronchial hyperresponsiveness are key
      factors. The plasma exudate from the microvascular leakage plays a significant
      role in remodelling, which includes extracellular matrix (ECM) protein
      deposition/breakdown and airway smooth muscle (ASM) hyperplasia/hypertrophy. 2.
      The ECM is an intricate network of macromolecules that forms the 'scaffolding' of
      the airways. This scaffolding not only acts as mechanical support that plays a
      crucial role in the maintenance of airway function and structure, but it is also
      a dynamic and complex network that has the potential to influence cellular
      function, including migration, differentiation and proliferation of a number of
      cell types. 3. In asthmatic airways, the profile of ECM proteins is altered. The
      deposition of collagen I, III, V, fibronectin, tenascin, hyaluronan, versican and
      laminin alpha2/beta2 is increased, whereas the deposition of collagen IV and
      elastin is decreased. 4. This imbalance in the ECM profile within the asthmatic
      airway could be due to: (i) increased de novo synthesis of ECM proteins; (ii)
      decreased activity of its degrading enzymes, namely matrix metalloproteinases
      (MMP); or (iii) upregulation of the tissue-specific inhibitors of
      metalloproteinases (TIMP). 5. One of the characteristic features of asthma is an
      increase in the amount of ASM within the airways. The ECM proteins/MMP/TIMP in
      and around the smooth muscle may play a contributory role in this increased
      growth. 6. The role of current asthma treatments in the prevention or reversal of
      airway ECM changes is an area that has only recently become of interest, with the
      majority of the in vivo work focusing on the effects of corticosteroids. 7. The
      evidence presented in this review indicates that the ASM may influence its own
      environment/proliferation through the production of ECM proteins, MMP and TIMP.
      Further studies are needed to fully understand the role of the ASM in the
      production of ECM proteins, MMP and TIMP andtheir potential influence in the
      mechanisms underlying asthma.

PMID- 11236133
TI  - Intrapituitary interactions: another level of endocrine regulation.
AB  - 1. Factors, produced within the anterior pituitary, act locally to influence many
      acute and developmental changes in neighbouring cells. 2. Broad spectra of
      factors and activities characterize these paracrine interactions. 3. Cleavage
      products of pro-opiomelanocortin, other than those that act as systemic hormones,
      are produced by neonatal gonadotrophs and these peptides stimulate mitosis and
      differentiation of lactotrophs. 4. Activins and follistatins exert opposing
      effects on gonadotrophs. The stimulatory activity of activins is modulated
      extracellularly through protein-protein interactions with follistatin. Within
      gonadotrophs, the stimulatory activity of activins is self-limiting through
      receptor-mediated stimulatory and inhibitory signal transduction pathways. 5.
      During the oestrous cycle, the interactions between gonadotroph cells and
      epidermal growth factor (EGF), acting as a local signal, occur on multiple
      levels. Levels of expression of EGF receptors on cells vary as a function of the
      cycle, as do EGF-induced changes in gene expression and proliferation of cells.

PMID- 11236134
TI  - Growth and differentiation factors derived from the N-terminal domain of pro
      opiomelanocortin.
AB  - 1. We describe a novel paracrine control system in the pituitary gland,
      consisting of peptides derived from the N-terminal fragment of pro
      opiomelanocortin (N-POMC), for example POMC(1-74) and gamma3-melanocyte
      stimulating hormone (MSH). 2. By searching the target cells of these N-POMC
      fragments, using the rise of intracellular free calcium as a response system and
      single cell reverse transcription-polymerase chain reaction of hormone mRNA as a
      cell type identification method, we found that a considerable number of cells in
      normal rat pituitary display combinatorial expression of different pituitary
      hormone genes (further referred to as 'multihormone mRNA cells'), without
      indication that all these cells also produce or store the respective hormones
      translatable from these mRNA. The N-POMC fragments POMC(1-74) and gamma3-MSH
      preferentially target particular subsets of these multihormone mRNA cells. 3. We
      discovered a potentially novel receptor for gamma3-MSH on these cells; more
      precisely, on cells coexpressing growth hormone and prolactin. The putative novel
      receptor displays properties highly divergent from those of the known gamma3-MSH
      receptor (i.e. the melanocortin-3 receptor) and even of all other melanocortin
      receptors cloned today.

PMID- 11236135
TI  - Actions of activins, inhibins and follistatins: implications in anterior
      pituitary function.
AB  - 1. The anterior pituitary is well documented to be under the control of central
      and peripheral factors that dynamically interact to affect cell-specific
      modulation of pituitary functions. However, it is becoming increasingly evident
      that these extrinsic factors work in concert with a variety of local products
      that exert autocrine/paracrine control on pituitary cells. 2. These factors
      modulate the activity of their target pituitary cells by altering the synthesis
      and secretion of cell-specific hormones and by exerting control on the growth and
      differentiation of cells of this tissue. Included in the list of growth factors
      and bioactive peptides known to be products of pituitary cells are the activins,
      possibly inhibins and follistatins. 3. These protein factors play an important
      role in the local modulation of several pituitary cell types and are crucial for
      the maintenance of normal follicle-stimulating hormone production and, thus,
      reproductive function and fertility.

PMID- 11236136
TI  - Sites of epidermal growth factor synthesis and action in the pituitary: paracrine
      and autocrine interactions.
AB  - 1. Epidermal growth factor (EGF) is produced by growth hormone (GH) cells and
      gonadotropes in normal pituitary cell populations. The studies were initiated to
      determine whether EGF is a paracrine or autocrine regulator of gonadotrope
      function. 2. The first group of studies tested for the presence of EGF receptors
      in gonadotropes from cycling female rats by immunolabelling. Expression varied
      with the stage of the cycle. At the highest point (metoestrus), only a few EGF
      target cells are gonadotropes, identified by their content of luteinizing hormone
      (LH)-beta mRNA. Expression by gonadotropes then increased to reach a peak of 50%
      of cells during pro-oestrus. 3. Studies investigating the regulation of
      expression of EGF receptor (R) showed that all culture conditions (in media with
      or without serum) and EGF itself both stimulated expression of the receptor by
      gonadotropes in populations from oestrus or metoestrus rats. Gonadotropin
      releasing hormone (GnRH) also stimulated EGFR expression in follicle-stimulating
      hormone (FSH) gonadotropes from oestrus animals. Additional tests of expression
      of immediate early genes (c-fos) showed that, after 15 min, EGF stimulated
      expression in cells with FSH antigens. 4. Epidermal growth factor also stimulated
      gonadotrope proliferation, as detected by the MTT cell growth/cell death assays
      and bromodeoxyuridine uptake by gonadotropes during the S phase (DNA synthesis)
      of the cell cycle. 5. Epidermal growth factor and GnRH both stimulated a
      significant increase in the percentage of mitotic gonadotropes. Epidermal growth
      factor may be an autocrine or a paracrine growth factor to maintain and develop
      the gonadotrope population and EGF may also be involved in early differentiation
      events that prepare cells to support the LH surge.

PMID- 11236138
TI  - [Morphological structure of the teeth in patients with rapidly-progressing
      periodontitis].
AB  - Analysis of panoramic radiographs taken from 60 patients with rapidly progressive
      (RPP) and 40 patients with typical moderate-severe periodontitis (TP) revealed
      anatomical peculiarities. Measurement of tooth proportions showed high prevalence
      of morals with short narrow and short distant roots in patients with RPP as
      compared with TP. Also in patients with RPP the mesial surface of the first
      morals was involved more often than the distal one, furcations were involved
      particularly in molars with descent short roots. Investigation of anatomical
      peculiarities can be used to explain atypical forms of periodontal diseases.

PMID- 11236137
TI  - [Clinical histochemistry of the barrier function of gingival mucosa in
      periodontitis].
AB  - Parodontium was investigated in 111 persons. The components of gingiva mucosa
      tissue barrier are presented. The biopolymers dynamics is revealed in
      periodontosis in its aggravation. The research, allowing to judge the resistance
      of parodontium, is recommended.

PMID- 11236139
TI  - [Status of oral mucosa and periodontal tissue in children with gastroduodenal
      diseases associated with Helicobacter pylori].
AB  - General and dental status was evaluated in 64 children aged 5-14 years with
      active chronic gastroduodenitis and gastroduodenal ulcer. Helicobacter pylori was
      detected by the urease test and morphological analysis of gastric biopsy
      specimens with subsequent Giemsa or toluidine blue staining. The presence of
      Helicobacter pylori was confirmed by immunohistochemical analysis with monoclonal
      antibodies to this bacterium using DAKO kits. Children with gastroduodenal
      diseases often suffer from chronic catarrhal gingivitis liable to generalization
      and often develop pronounced changes in the mucosa of the tongue and red lips.

PMID- 11236140
TI  - [Effect of masticatory load on oxygen tension in periodontal tissues].
AB  - Relationship between the effect of occlusional loading (weak, 10-15 H, and
      strong, 120-150 H) and oxygen tension (pO2) in periodontal tissues adjacent to
      the first molar on the working and resting sides was carried out in 57 subjects
      with different clinical status of the periodontium and with partial secondary
      adentia. pO2 decreased during exercise, the most pronounced drop (to 12 mm Hg)
      being observed during intensive exercise. The level of pO2 decreased greater on
      the resting side and in patients with periodontal diseases. The longest period of
      pO2 recovery (up to 50 min) was observed after intensive exercise.

PMID- 11236141
TI  - [General somatic aspects of pathogenesis and treatment of generalized
      periodontitis].
AB  - Generalized periodontitis is a polyetiological disease, pathogenetically bound
      with internal pathology. The study was made to reveal common somatic mechanisms
      of generalized periodontitis pathogenesis. The examination of 574 patients has
      established immunological unbalances, mineral deficiencies and high activity of
      free radical oxidation of lipids and proteins. The usage of systemic multienzyme
      remedies, replacement mineral therapy, antioxidants, had correcting effects. This
      evidences for the presence of close links between pathogenetic mechanisms of
      generalized periodontitis, functioning according to the mobile's principle.

PMID- 11236142
TI  - [Comprehensive approach to diagnosis and treatment of chronic generalized
      periodontitis].
AB  - The article presents the new investigation technique of parodontium examination
      and treatment. The trials proved the high efficacy of low molecular
      polyvinylpyrrolidone, antioxidantes, antihypoxants, application sorbites, low
      temperature plasma flow argon and surgical interventions.

PMID- 11236143
TI  - [Integral coefficient characterizing free radical oxidation and antioxidant
      defense, and the new "residual" coefficient reflecting the efficiency of using
      antioxidants in periodontitis].
AB  - The new integral coefficient between free-radicals oxidation (FRO) and
      antioxidant defense (AOD) during periodontitis is offered. This "residual" index
      may be used for evaluation of the decrease or increase in the balance between FRO
      and AOD in different fluids and organs under different conditions.

PMID- 11236144
TI  - [Dynamics of immunologic indicators of the oral cavity during treatment of
      inflammatory periodontal diseases in insulin-dependent diabetes mellitus].
AB  - The article describes the results of examination of 42 patients with inflammatory
      periodontal disease (IPO) and insulin-dependent diabetes mellitus (IDDM). It is
      shown, that the effect of treatment of IPO depends on a degree of compensation of
      carbohydrate metabolism: it is quite satisfactory in compensated and
      unsatisfactory in decompensated IDDM. In saliva of patients with IPO the antigen
      of damaged periodontal tissues, antibody to it, and also immune complexes Ag-Ab
      are found. The frequency of these parameters and their dynamics after treatment
      of IPO depends on a degree of compensation of carbohydrate metabolism in IDDM.
      The antibodies and immune complexes do not play a pathogenic role and can be used
      for prognosis and success of IPO treatment.

PMID- 11236146
TI  - [Key components of pathogenesis of periodontal diseases in light of
      cytomorphological findings].
AB  - A new cytomorphometrical method for evaluation of periodontal status by cytograms
      of gingival impressions is based on estimation of destruction index and
      inflammatory destructive index. This method will be helpful in the diagnosis of
      periodontal diseases, monitoring of the pathological process after treatment, and
      in solution of theoretical problems, e.g. investigation of the key factors in the
      pathogenesis of periodontal diseases. The authors analyze the relationship
      between the two major components of pathogenesis of periodontal inflammation
      inflammatory infiltrative process and destructive changes.

PMID- 11236145
TI  - [Effectiveness of treating periodontitis in patients with thyroid dysfunction].
AB  - Efficiency of some drugs in the treatment of periodontitis in combination with
      corrective treatment of thyroid function was evaluated in 70 patients with hypo-
      and hyperthyrosis with different initial level of nonspecific resistance. The
      therapeutic complex including drugs commonly used in the treatment of
      periodontitis and irrigation of the periodontium with lithium chloride and
      chlorohexidine solutions was highly effective in patients with thyroid
      dysfunction and relatively favorable status of nonspecific resistance of the
      organism. In patients with hypo- and hyperthyrosis with poor nonspecific
      resistance the best effect in the treatment of periodontitis was attained with
      potassium orotate as an immunomodulator and lithium chloride.

PMID- 11236147
TI  - [Functional activity of neutrophils and elastase inhibitory activity of blood
      serum and periodontal tissues during lymphotropic therapy of rapidly-progressing
      periodontitis].

PMID- 11236148
TI  - [Use of immunotherapy with bacterial allergens in the combined treatment of
      periodontitis].
AB  - Bacterial allergens were used in the treatment of patients with chronic
      generalized slight and medium severe periodontitis. The allergens were used for
      hyposensitization or immunostimulation, depending on skin reactions to
      staphylococcal, streptococcal, and Escherichia coli allergens. Positive shifts in
      nonspecific immunity were attained; bacterial sensitization decreased, which
      indicates the treatment efficiency.

PMID- 11236150
TI  - [Combined therapy of chronic catarrhal gingivitis using low intensity laser
      light].
AB  - Periodontal diseases, one of which is chronic catarrhal gingivitis (CCG),
      represent a medicosocial problem. Standard therapy often fails to bring about
      stable results. Addition of low-energy laser exposure at wavelengths of 0.63
      micron and 0.85-0.89 micron to therapeutic complexes helps attain stable results,
      which is confirmed by clinical, functional, immunological, and x-ray data and
      densitometry. Laser therapy exerts a multifactorial pathogenetic effect,
      eliminating inflammation in periodontal tissue, normalizing microcirculation in
      the periodontium, improving mineral saturation of osseous tissue of the alveolar
      processes of the jaws, and improving local immunity of the oral cavity. All this
      accelerates treatment and decreases the probability of relapses.

PMID- 11236149
TI  - [Treatment of inflammatory diseases of the periodontium using immobilized
      indomethacin].
AB  - Analysis of treatment results of inflammatory periodontal diseases with different
      drugs has shown high effectiveness of immobilized on polysorb indomethacin in the
      treatment of gingivitis and periodontitis.

PMID- 11236151
TI  - [Experience in treating chronic periodontal diseases with vilprafene
      (josamycin)].
AB  - Forty-two patients with chronic generalized periodontitis were treated. Thirty
      five patients presented with exacerbation of the disease of second-third degree
      of severity, clinically manifesting with hyperemia, edema of the gingival mucosa
      with pyorrhea from the gingivodental pouches, and mobility of teeth of the second
      third degree; exacerbation of the process with abscesses round 1-2 teeth was
      observed in 4 patients, abscesses in the periodontal bone in 2, and edematous
      hypertrophic gingivitis in 1 patient. All patients were treated with vilprafene.
      Pyorrhea ceased, hyperemia and edema of the gingival mucosa resolved after
      treatment in 39 (92.8%) patients.

PMID- 11236152
TI  - [Possibilities of using laser doppler flowmetry in evaluating periodontal tissue
      status].
AB  - Laser Doppler flowmetry (LDF) was used for evaluation of microcirculatory
      disorders in periodontal tissue of children in health and disease. Gingival
      capillary bloodflow was examined in children and adults with intact periodontium
      and orthognathic occlusion, chronic generalized catarrhal gingivitis and local
      periodontitis (with evaluation of the efficiency of laser therapy), in children
      with various maxillodental abnormalities, and in adults with partial and complete
      adentia. LDF findings were processed using mathematical analysis, and criteria
      for evaluation of capillary bloodflow in children of different age groups were
      defined. LDF detects microcirculatory disorders in periodontal tissues and
      differentiates between them, detects subjects at a high risk of periodontal
      inflammations, helps monitor the treatment course and evaluate the disease
      severity.

PMID- 11236153
TI  - [A new optimizer of reparative regeneration in periodontal diseases].
AB  - The composition OSTEOSIT at a surgical stage of combined treatment of chronic
      generalized periodontitis was examined. The results in the control and study
      groups prove, that the composition OSTEOSIT allows to reduce time of treatment,
      to achieve remission of disease, to reduce amount of relapses.

PMID- 11236154
TI  - [Questions on the efficiency of membrane technology in treating periodontal
      diseases. Experience of experimental and clinical studies].
AB  - Experimental and morphological studies demonstrated that Gore Resolute resorbable
      membrane can cause local inflammatory reactions similar to allergic. Collagen
      based biomembranes coated with hydroxyapatite cause no local pathological
      reactions, but are rapidly resorbed in foci of degeneration under the effect of
      aggressive factors of tissue environment. Russian silicone membrane has been
      clinically tried with satisfactory results in patients with generalized
      periodontitis; the results prompt further studies of the membrane.

PMID- 11236155
TI  - [Status of the hemostasis system in periodontitis in patients with insulin
      dependent diabetes mellitus as criteria of disease severity and treatment
      efficacy].
AB  - Relationship between insulin-dependent diabetes mellitus complicated by
      periodontitis of different severity and the plasma and vascular-platelet
      components of hemostasis and blood rheology was studied with the aim of early
      diagnosis of coagulation disorders and evaluating their significance in the
      mechanism of thrombohemorrhagic complications. Clinical status of patients
      correlated with their blood clotting parameters, particularly so in severe
      periodontitis. For correction Bioplant was used to replace bone pouches in
      surgical treatment of periodontitis.

PMID- 11236156
TI  - [Use of a new biological factor--exogenous nitric oxide--during surgical
      treatment of periodontitis].
AB  - In order to improve the efficiency of surgical treatment of periodontitis, the
      operative wound was exposed to nitrogen oxide (NO) during osteogingivoplasty and
      on days 3, 5, and 6 after it. Clinical and laboratory data making use of the
      cytomorphometrical method indicate that NO exposure decreased and maybe prevented
      secondary injury to the operation wound in up to 46.6% patients, which was
      confirmed by decrease and even normalization of destruction index and
      inflammatory destructive index on days 7 and 14, which was not observed in the
      reference group patients not exposed to NO.

PMID- 11236157
TI  - [Results and prospects for combined treatment of periodontal diseases (clinico
      experimental study].
AB  - Combined treatment was studied of 169 patients with chronic generalised
      periodontitis in moderate or severe stages, including local pharmacological and
      laser therapy, selected teeth grinding, transdental implantation, splinting,
      immediate denture with preliminary collagen plastics of alveolar bone. Positive
      follow-up results confirmed by experimental data have been received.

PMID- 11236158
TI  - [Volatile compounds in air and oral saliva in healthy people, and in
      periodontitis and gingivitis patients].
AB  - 21 healthy persons, 7 patients with chronic generalized periodontitis and 4
      patients with chronic generalized gingivitis aged between 18 and 42 years were
      examined. Air from the oral cavity was collected with a special device; liquid
      samples were collected by washing the oral cavity with sterile water. Chemical
      compounds of the air and the washed liquid were analyzed by chromato-mass
      spectrometry, gas-adsorption and gas-liquid chromatography. The content of
      dimethyl sulphide, dimethyl disulphide increased in the oral air and such
      volatile short chain fatty acids (VSCFA) as butyrate, propionate, acetate rose,
      but their aldehydes (butyraldehyde, acrolein, acetaldehyde decreased in oral
      fluid during periodontitis. The concentration of these compounds were found to be
      between the levels in control persons and during periodontitis. The content of
      pentane decreased in oral air. That depended on the intensity of inflammation and
      vessel disturbances. The results suggest that VSCFA produced by Porphyromonas,
      Prevotella, Fusobacterium and other periodontopathic bacteria, penetrate the oral
      mucosa and severely harm the periodontal tissue. The increase of dimethyl
      sulphide contributed to oral malodor during periodontal inflammation.

PMID- 11236159
TI  - Introduction to transesophageal echocardiography (TEE) with a historical
      perspective.
AB  - Since its introduction in the early 1980s, TEE has become an important standard
      clinical tool with greatly expanded applications. The technique continues to
      develop. We can expect the future to bring reliable imaging of myocardial
      perfusion and user-friendly three-dimensional applications.

PMID- 11236160
TI  - Transesophageal echocardiographic (TEE) evaluation of ventricular function.
AB  - Transesophageal echocardiography (TEE) provides excellent delineation of
      ventricular function in the ambulatory and critical settings. Major indications
      include the acutely ill patient with suboptimal images with other techniques and
      the intraoperative assessment of patients undergoing cardiac surgery and of
      cardiac patients undergoing noncardiac surgery. The methodology of quantification
      of ventricular function is quite accurate, though it has inherent limitations.
      Newer technologies, such as edge enhancement techniques, three-dimensional
      acquisition, and contrast agents, all have the potential to improve evaluation of
      ventricular function with TEE. Stress imaging with TEE is possible with
      dobutamine and with pacing techniques. This is sage and accurate, and it is
      indicated in patients, such as the morbidly obese, who are impossible to image by
      other methods.

PMID- 11236161
TI  - Hemodynamics derived from transesophageal echocardiography (TEE).
AB  - Table 1 lists the parameters that are sought routinely in developing a complete
      hemodynamic profile by TEE. The arterial blood pressure is an essential starting
      point. Knowledge of the cardiac output (flow velocity integral) allows placement
      of the other parameters in context by providing a notion of the status of the
      general circulation and of the level of pulmonary and systemic vascular
      resistance. The mitral inflow allows segregation of the diastolic function of the
      left ventricle into one of three categories: (1) normal, (2) restrictive, or (3)
      delayed relaxation. Pulmonary vein inflow is complementary to mitral inflow and
      further confirms the status of the filling pressure. The MR jet is another means
      of gauging the systemic blood pressure and the filling pressure but is more
      technically demanding than recording mitral valve and pulmonary valve inflows.
      Tricuspid regurgitation, also technically demanding, reliably provides peak
      pulmonary systolic pressure, and PR provides the end-diastolic pulmonary artery
      pressure. Doppler [table: see text] flow in the great veins is useful in
      estimating right atrial pressure; this information must be integrated with TR and
      PR velocities to estimate pulmonary artery pressure. Finally, the motion and
      curvature direction of the IAS allows identification of the atrium with the
      higher pressure. Using the dynamic behavior of this structure enables
      reconstructing of the pressure in one atrium from knowledge of pressure in the
      other. As the case example shows, using these techniques in a routine fashion
      enables an accurate, comprehensive, and reliable qualitative assay of hemodynamic
      status.

PMID- 11236162
TI  - Transesophageal echocardiographic (TEE) evaluation of the aortic valve, left
      ventricular outflow tract, and pulmonic valve.
AB  - The most important role of TEE in aortic valve disease is in the diagnosis of
      endocarditis and its complications. Examination of the annulus and subvalvular
      region is essential in any patient with possible aortic valve endocarditis.
      Assessment of the severity of aortic stenosis is a useful application of TEE when
      other data are either inconsistent or unavailable. TEE can provide a diagnosis of
      the origin of acute severe aortic insufficiency; this information may play a
      critical role in surgical planning. The diagnosis of a variety of aortic valve
      diseases can be made when TEE is performed to find an embolic source or to rule
      out dissection. In the case of mass lesions, such as papillary fibroelastomas and
      Libman-Sacks vegetations, the results of TEE carry major therapeutic
      implications. TEE offers generally excellent quality images of the LVOT and
      images of the RVOT and pulmonic valve that are superior to transthoracic
      echocardiography. The major clinical usefulness of TEE stems from its ability to
      identify pulmonic valve mass lesions and the causes of left and right ventricular
      outflow obstruction. TEE is also an important adjunct in the surgical management
      of left ventricular outflow obstruction.

PMID- 11236163
TI  - Transesophageal echocardiographic (TEE) evaluation of the mitral and tricuspid
      valves.
AB  - In skilled hands, multiplane TEE provides a comprehensive assessment of the
      anatomy and function of the mitral and tricuspid valves. TEE is uniquely
      effective in the evaluation of the diverse pathophysiologic processes that cause
      valvular heart disease.

PMID- 11236164
TI  - Transesophageal echocardiographic (TEE) evaluation of prosthetic valves.
AB  - TEE overcomes many of the imaging constraints associated with transthoracic
      echocardiography for the assessment of valvular anatomy and function. Additional
      imaging artifacts and constraints associated with prosthetic valves are minimized
      or overcome with TEE. As such, TEE allows assessment of prosthetic valve anatomy
      and function and paraprosthetic anatomy, and serves as the diagnostic imaging
      modality of choice for patients with suspected prosthesis dysfunction or
      endocarditis.

PMID- 11236165
TI  - Transesophageal echocardiography (TEE) in the evaluation of infective
      endocarditis.
AB  - Echocardiography is an essential tool for the modern diagnosis and management of
      infective endocarditis and its complications. The negative predictive value of
      surface imaging is inadequate to rule out endocarditis in most instances;
      diagnostic sensitivity is improved by way of the transesophageal approach. The
      clinical scenario and pretest probability of disease should guide the use of
      transesophageal versus transthoracic imaging. Those at high risk for endocarditis
      or its complications in particular should undergo early TEE. Serial studies may
      be required to guide management. In the setting of an initially negative
      echocardiographic study, a repeat examination is indicated if the clinical
      suspicion of endocarditis persists or if the clinical picture changes. Combined
      transthoracic echocardiography and TEE may supply complementary information
      useful in management and follow-up. As most published research predates recent
      advances in imaging, the impact of changing technology, such as harmonic and
      three-dimensional imaging, in the management of endocarditis is yet to be
      determined.

PMID- 11236166
TI  - Transesophageal echocardiography (TEE) in the critical care patient.
AB  - Critically ill patients often pose special diagnostic problems to the clinician,
      intensified by limited physical examination findings and difficulty in
      transportation to imaging suites. Mechanical ventilation and the limited ability
      to position the patient make transthoracic echocardiography difficult.
      Transesophageal echocardiographic (TEE) imaging, however, is well suited to the
      critical care patient and is frequently used to evaluate hemodynamic status, the
      presence of vegetations, a cardioembolic source, and an intracardiac cause of
      hypoxemia. Using proper precautions, TEE can be performed safely in unstable
      patients and frequently leads to important changes in management.

PMID- 11236167
TI  - Aortic dissection.
AB  - Aortic dissection is a life-threatening cardiovascular emergency requiring
      immediate diagnosis and treatment. It is mainly associated with hypertension and
      the Marfan syndrome. Diagnosis has been revolutionized by the use of
      transesophageal echocardiography (TEE), which allows for rapid and safe
      assessment of this condition. Echocardiographic hallmarks of aortic dissection ar
      the presence of a dissection membrane separating a true from a false lumen,
      rupture sites in the membrane with to-and-from flow, aortic regurgitation, and
      pericardial effusion. Dissection of the ascending aorta, which has an extremely
      high mortality and necessitates emergency surgery, is diagnosed quickly and
      accurately by TEE.

PMID- 11236168
TI  - Transesophageal echocardiography (TEE) in atrial fibrillation.
AB  - Transesophageal echocardiography has given new insight into the pathogenesis of
      the thromboembolic sequelae of AF and expanded the available therapeutic options.
      Studies to date indicate that TEE-guided cardioversion is a safe and reasonable
      approach when the clinical situation warrants prompt restoration of sinus rhythm.
      Whether widespread use of this strategy offers further benefit remains to be
      established, although there are theoretical advantages to such an approach. The
      potential for earlier cardioversion using a TEE-guided approach may facilitate
      the achievement and maintenance of sinus rhythm. In the long term, earlier
      restoration of sinus rhythm prevents adverse atrial remodeling, lowers embolic
      risk, and may improve cardiac performance and functional status. Thromboembolic
      sequelae (either cardioversion-related or as a result of chronic AF) remain the
      most devastating complications of AF. Every attempt to minimize this risk should
      be pursued aggressively. Information gathered from TEE has helped to elucidate
      the mechanisms responsible for postcardioversion embolism and has emphasized the
      importance of anticoagulation during and after the restoration of sinus rhythm.
      TEE also has the potential to further risk stratify patients with AF. Ultimately,
      a subset of patients may be identified who require more intense anticoagulation
      (i.e., those with dense SEC or thrombus, or persistent thrombus after prolonged
      anticoagulation) or in whom cardioversion may be deferred entirely. Likewise, TEE
      also may prove to be useful in identifying patients with a low-clinical risk
      profile who may be treated with aspirin alone and patients in whom warfarin may
      be superior. The results of the ACUTE study should help to further define the
      role of TEE in the management of patients with AF. Additional clinical studies
      are needed to address some of the issues that have been raised and to allow for
      optimal use of TEE in this patient population.

PMID- 11236169
TI  - Transesophageal echocardiography (TEE) in the evaluation of the coronary
      arteries.
AB  - With technical advancements, including high frequency, multiplane transducers,
      digital acquisition and display, and left-sided contrast agents, TEE is emerging
      as a promising method for evaluating coronary artery disease. Visualization of
      proximal coronary artery stenoses and coronary artery anomalies is already
      possible. Research studies using TEE measurement have contributed to
      understanding coronary artery physiology and may prove to be a valuable clinical
      tool in the future.

PMID- 11236170
TI  - Transesophageal echocardiographic (TEE) evaluation of intracardiac and
      pericardial masses.
AB  - Transesophageal echocardiography has assisted the detection of intracardiac
      masses and, in certain cases, aided our ability to define the specific type of
      mass. This technique, when coupled with three-dimensional imaging, may help to
      define infiltration of the wall. TEE aids in the intraoperative management of
      cardiac tumors.

PMID- 11236171
TI  - Transesophageal echocardiography (TEE) in congenital heart disease with focus on
      the adult.
AB  - Remarkable innovations in medical and surgical approaches over the past several
      decades now allow for correction of major cardiac defects in children, even in
      early infancy. These advances have provided for survival of many pediatric
      patients with congenital heart disease into adulthood. Although transthoracic
      echocardiography remains the primary imaging technique for the characterization
      of simple and complex congenital cardiovascular malformations in the pediatric
      and adult age groups, high-resolution transesophageal imaging has markedly
      expanded the anatomic and hemodynamic assessment in these patients. The benefits
      of this imaging approach apply particularly to those with challenging or limited
      transthoracic examinations or poorly characterized congenital cardiovascular
      malformations. The utility of TEE in defining the anatomy of the usual spectrum
      of congenital cardiac malformations is well established. The transesophageal
      approach has been shown to provide additional diagnostic information over
      conventional transthoracic imaging for specific structural cardiac anomalies and
      in the perioperative setting, the opportunity for confirmation of preoperative
      diagnoses, and modification of the surgical plan if new or different pathology is
      identified. This imaging modality also may reliably provide for immediate
      detection of suboptimal surgical repairs and significant postoperative residua,
      potentially improving the efficacy of the surgical intervention. This accounts
      for the vital role of this technology in perioperative management and integration
      into the standard of care in many congenital heart centers. The usefulness of TEE
      also has been documented during diagnostic and therapeutic cardiac
      catheterizations of patients with structural cardiac anomalies, allowing for
      safer and more effective application of these technologies. The experience
      supports the use of TEE as a useful approach in the surveillance of the adult
      with operated and unoperated congenital heart disease.

PMID- 11236172
TI  - Three-dimensional transesophageal echocardiography (TEE) and other future
      directions.
AB  - As faster imaging systems enter the market, three-dimensional echocardiography is
      gearing up to become a useful tool in assisting the clinician to image the heart
      in many innovative projections. What started out as a novel idea of displaying a
      three-dimensional anatomic picture of the heart now provides a multitude of views
      of the heart and its structures. Information gained from anatomic and dynamic
      data has helped clinicians and surgeons in making clinical decisions. In the
      future, this imaging modality may become a routine imaging modality for assessing
      cardiac pathology and may serve to increase understanding of the dynamics of the
      heart.

PMID- 11236173
TI  - Is the society on its cruising speed?

PMID- 11236174
TI  - The quality of surgery: challenges and controversies.

PMID- 11236175
TI  - The sentinel node concept in melanoma and breast cancer: relevancy and
      therapeutic consequences.

PMID- 11236176
TI  - Economic considerations for aortic surgery: retroperitoneal approach--is it worth
      it?
AB  - BACKGROUND: Planned reductions in reimbursement for all forms of vascular surgery
      dictate a need for the development of more cost efficient, yet quality oriented,
      treatment programs. We are faced with an increasingly older patient population
      with multiple comorbidities. In this environment it will become extremely
      difficult to accomplish aortic surgery in a way which will be profitable for our
      hospitals. More than 100,000 aortic surgeries are performed annually in the
      United States. Previous reports suggest that earlier hospital discharges and
      reduced postoperative complications occur when a retroperitoneal approach is used
      for aortic surgery. Other publications refute this concept. In an effort to
      determine the most cost efficient method for aortic surgery in our institution,
      while maintaining high standards of care and outcome, we compared the
      retroperitoneal approach to the conventional transperitoneal aortic operation.
      PATIENTS AND METHODS: Between December 1995 and April 1998, 120 patients
      underwent aortic surgery by either the transperitoneal (n = 60) or
      retroperitoneal approach (n = 60). All patients were enrolled prospectively in a
      vascular registry and retrospectively reviewed. Patients were randomly assigned
      to one of three vascular surgeons. A clinical pathway for elective aortic surgery
      was developed and applied to both groups. Patients were evaluated with respect to
      demographics, comorbidities, preoperative risk stratification, conduct of the
      operative procedure, length of stay, complications, cost, clinical outcomes and
      patient satisfaction. The indications for aortic surgery were similar in both
      groups--64% for aneurysm disease and 36% for occlusive disease. Both symptomatic
      and asymptomatic aneurysms were included and size ranged from 4.4 cm to 14 cm.
      All aortic reconstructions were done in the standard manner using knitted Dacron
      velour prostheses in either the aortic tube, bi-iliac or bi-femoral
      configuration. Statistical analysis of means and medians was accomplished using
      the Wilcoxin Rank-sum test and percentages were compared using Fisher's Exact
      test. P values less than 0.05 indicate statistical significance. RESULTS: There
      were no statistically significant differences in patient demographics. The
      incidence of atherosclerotic coronary artery disease, obstructive pulmonary
      disease, diabetes, hyperlipidemia, tobacco abuse, distal lower extremity
      occlusive disease and the results of chemical myocardial stress evaluations were
      similar in both groups. Comorbidities of preexisting renal insufficiency/failure
      and morbid obesity were increased in the retroperitoneal group. Five patients in
      the retroperitoneal group represented redo aortic surgery and there were no redo
      procedures in the transperitoneal group. Length of operative procedures and blood
      replacement requirements for both groups were similar. The transperitoneal group
      required 2-3 liters more intraoperative intravenous (i.v.) crystalloid than the
      retroperitoneal group (p < 0.0001). Statistically significant reductions in ICU
      days, postoperative ileus and total lengths of stay were observed in the
      retroperitoneal group (p < 0.0001). This resulted in substantial reductions in
      hospital costs for the retroperitoneal group (p < 0.01). Postoperative
      complications were similar for both groups except for statistically significant
      increases in pulmonary edema (p < 0.01) and pneumonia (p < 0.001) in the
      transperitoneal group. Cardiac arrhythmias, primarily atrial dysrhythmias, were
      more frequent in the transperitoneal group but this failed to reach statistical
      significance (p < 0.16). Combined thirty day mortality was 0.9%. Time of recovery
      to full activity and patient satisfaction substantially favored the
      retroperitoneal group. CONCLUSION: Our clinical pathway and algorithm for aortic
      surgery was easily followed by those patients in the retroperitoneal approach
      group and resulted in decreases in ICU time, postoperative ileus, volume of
      intraoperative crystalloid and total length of stay. The patients in the
      transperitoneal group often failed to progress appropriately on the pathway.
      Reduced hospital costs associated with aortic surgery using the retroperitoneal
      approach has increased the profitability for this surgery in our institution by
      an average of $4000 per case and has increased the value (quality/cost) of this
      surgery to our patients and our institution. This was accomplished in an academic
      environment with surgical residency training where cost containment has
      historically been difficult.

PMID- 11236177
TI  - To stent or not to stent in the iliac artery?

PMID- 11236178
TI  - New information on the value of plaque characterisation--relation to symptoms.
AB  - This paper reviews the literature on the significance of carotid plaque
      echomorphology and degree of stenosis in relation to the different types of
      cerebrovascular symptomatology (amaurosis fugax, hemispheric transient ischaemic
      attacks, stroke) and the asymptomatic status. It provides evidence that amaurosis
      fugax is associated with hypoechoic and severely stenosed plaques, the
      hemispheric transient ischaemic attacks and stroke are associated with plaques of
      intermediate echodensity and stenosis while the asymptomatic status is associated
      with hyperechoic and moderately stenosed plaque. It lends support to the notion
      that plaque hypoechoicity is associated with embologenicity. It supports the view
      that the severe carotid stenosis facilitates the opening of the cerebral
      collateral circulation and that amaurosis fugax is associated with an "opened"
      cerebral collateral supply as contrasted to the cerebrovascular symptomatology.
      It proposes the inclusion of the cerebral collateral circulation as a stroke risk
      factor along with the plaque echomorphology and the degree of stenosis in the
      natural history studies of asymptomatic individuals with carotid bifurcation
      plaques.

PMID- 11236179
TI  - Mediastinal goitres: when the transthoracic approach?
AB  - The correct surgical approach to mediastinal goitre is not always well defined.
      We reviewed why and when our patients required a transthoracic approach. From
      1979 to 1998, on 7.480 patients who underwent thyroid surgery in our hospital,
      374 (5%) had a goitre whose greater bulk was inferior to the thoracic inlet; 43
      patients of these last ones (11%) required a transthoracic approach. General
      anaesthesia was performed in all patients and orotracheal intubation was
      selective in 11 cases (double lumen tube of Carlens). In 34 cases, the first
      approach was a cervicotomy, followed by sternotomy in 23 cases or right
      posterolateral thoracotomy in 11 cases. Three patients underwent a sternotomy and
      6 a thoracotomy only. We had neither perioperative mortality nor major
      complications. The mean hospital stay was 5 days. Mean goitre weight was 430 g
      and on average the greater diameter was 13 centimetres. The removal of a
      substernal goitre can be difficult and risky via the cervicotomy only. A
      transthoracic approach is often required in the case of greater secondary,
      primary and recurrent mediastinal goitres.

PMID- 11236180
TI  - Liver transplantation in an era of organ shortage.

PMID- 11236181
TI  - Non beating heart donors as a possible source for liver transplantation.
AB  - Organ shortage for liver transplantation continues to be a major problem. Non
      heart beating donors (NHBD) are gaining increasing importance as a potential
      source of transplantable organs for clinical use, mainly in kidney
      transplantation. Up to now, the experience in liver transplantation with this
      type of donors has been limited and has only been considered in donors in whom
      cardiac arrest (CA) has occurred at a known given time. This is due to the high
      risk of primary non-function and late complications related to intrahepatic
      biliary lesions when warm ischemia time (WIT) is not controlled. The method of
      retrieval of these organs should offer the possibility to stop liver injury,
      revert histologic lesions appeared after WIT, and to assess the quality of the
      potential donor liver. Based on the experience of kidney transplantation, total
      body cooling achieved by extracorporal cardiopulmonary bypass seems to be the
      best method. Moreover it allows the inclusion of a time for tissue oxygenation at
      37 degrees C (Normothermic Recirculation, NR) prior to body cooling which has
      been shown to improve graft viability, and also allows a time to measure organ
      quality before transplantation. In our experience, we demonstrated that liver
      transplantation from NHBD is feasible; NR has beneficial effect on liver
      viability improving endothelial cell damage, hepatocyte energy charge and
      histological changes at 5 days. We also showed that time of cardiac arrest is
      determinant of graft viability; even if hepatocellular function is preserved
      after 40 minutes of CA using NR, irreversible intrahepatic biliary lesions are
      always present and burden long-term survival. Moreover, bypass pump and blood
      flows are directly related to WIT and the achievement of better pump flows may
      predict survival during NR. In animals with 40 minutes of CA, we also reported
      the possibility to manipulate the potential graft during NR with L-Arginine,
      Glycine and S-Adenosyl-Methyonine, which minimize endothelial and hepatocellular
      damage as well as lesions at 5 days. Further research needs to be done in order
      to confirm our experimental data.

PMID- 11236182
TI  - Technical and physiological limits of split liver transplantation into two
      adults.

PMID- 11236183
TI  - Bioartificial liver support: recent advances.

PMID- 11236184
TI  - Living donor adult liver transplantation: status quo in Kyoto and perspectives in
      the new millennium.
AB  - Through the technical evolution and excellent results in living related liver
      transplantation in children, living related/unrelated liver transplantation in
      adults has come into reality. Disadvantages of small-for-size liver grafts are
      now significantly mitigated by the repertoire of left lobe, right lobe, and whole
      left liver grafts. Evolution of living donor liver transplantation in adults,
      however, has disclosed significant controversies about anatomical aspects and
      physiology of the liver. This article summarizes our experiences in the past 5
      years and discusses still unresolved problems and perspective in the future.

PMID- 11236185
TI  - Sharing split liver grafts.

PMID- 11236186
TI  - Criteria for liver graft allocation in the era of organ shortage.

PMID- 11236187
TI  - Gene therapy to reduce portal hypertension: possible bridge to liver
      transplantation.

PMID- 11236188
TI  - Modified splitting technique for liver transplantation in adult-sized recipients.
      Technique and preliminary results.
AB  - In the common split liver technique the liver is divided between the right lobe,
      to be transplanted to an adult, and the left lateral segment, to be transplanted
      to a small child. We have developed an alternative technique by which the cadaver
      donor liver is divided in its two anatomo-functional halves, both apt to be
      transplanted to adults or children of adult size. We have so far used this
      technique in three multi organ donors, generating, six liver grafts that we
      transplanted to six recipients with median age of 36.5 years (range 10-23) and a
      median weight of 55 kg (range 38-79). Patient survival was 83.3% and graft
      survival 66.6% with a median follow up of 10 months (range 8-14). These results
      show that the technique is effective and that it can consistently increase the
      number of liver grafts that can be transplanted into adult patients, with the
      available cadaver donor pool.

PMID- 11236189
TI  - Marketing the rural hospital-based laboratory: building a customer-centered
      outreach program.
AB  - Rural hospital laboratories, which operate 24 hours/day, 7 days/week to meet
      inpatient and emergency-room care requirements, are situated uniquely to provide
      outpatient laboratory services for their communities. Laboratory managers looking
      to augment current services should consider implementing an outreach program.
      This article will explore the marketing aspects involved with developing a
      customer-centered outreach program, including finding a market niche, developing
      a business plan using elements of the consumption chain, addressing customer
      service issues, and business plan testing and validation.

PMID- 11236190
TI  - Clinical laboratory test menu changes in the Pacific Northwest: an evaluation of
      the dynamics of change.
AB  - To characterize changes in on-site test volumes and test menus and to identify
      the factors influencing these changes, we gathered information from a network of
      clinical laboratories in the Pacific Northwest in 1996 and again in 1999. The two
      studies allow for a snapshot of these changes for specific periods and also an
      evaluation of the dynamics of change in clinical laboratory practices between
      1994 and 1999. Throughout this 5-year span, business-related decisions have had
      the primary influence in determining where testing is performed. The overwhelming
      factor in deciding to retain certain tests on-site is whether the patient test
      volume is adequate to be cost-effective. Decisions to add or delete tests also
      are closely tied to marketplace competition, costs of testing equipment and
      supplies, and ability to obtain adequate reimbursement. Laboratory regulations
      have had a decreasing influence on on-site test menus in the network laboratories
      and particularly in physician office laboratories (POLs). The use of waived tests
      has increased dramatically, with POLs accounting for the majority of laboratories
      that added waived tests.

PMID- 11236191
TI  - Pre-analytical workflow analysis reveals simple changes and can result in
      improved hospital efficiency.
AB  - Workflow analysis is an ongoing process for laboratory managers. Throughout the
      years, laboratory managers have made many changes such as creating a core
      laboratory, consolidating technology, and implementing a new laboratory
      information system, all of which will have an immediate impact on laboratory
      operations. However, after implementation of any change in the laboratory, one
      should follow up with a pre- and/or postanalytical workflow assessment. This case
      study evaluates the pre-analytical impact of analytical changes made more than a
      year ago.

PMID- 11236192
TI  - Blood sample volumes: emerging trends in clinical practice and laboratory
      medicine.
AB  - Blood loss because of phlebotomy for diagnostic laboratory tests is a well
      recognized risk to neonates, particularly low-birthweight infants. In contrast,
      the risk of anemia from blood drawing in adults is relatively poorly studied. A
      few clinical studies have demonstrated the magnitude of this issue for critical
      care patients; most adult patients can easily tolerate the loss of blood volumes
      typically used for laboratory tests. Recommendations for promoting blood
      conservation in adults who frequently are phlebotomized include using smaller
      collection tubes, but more importantly organizing blood draws to eliminate
      duplicate and other unnecessary test requests and consolidating multiple
      collections into as few as possible by scheduling them. Emerging trends in
      medicine that will bear on the practice of blood conservation are "bloodless
      surgery," standardization of collection tubes for laboratory automation systems,
      and smart laboratory information systems that provide instant feedback to
      ordering physicians.

PMID- 11236193
TI  - Financial impact of work process redesign: experiences of four transfusion
      services.

PMID- 11236194
TI  - Strategic planning in a clinical environment.

PMID- 11236195
TI  - Mission possible: simplify your life.
AB  - Wanting a simpler life is not some late 20th century phenomenon.  It is not a new
      age fad, and it didn't start in California.  The quest for simpler living has
      been around since at least the time of the founding fathers.  This article
      explains why life has become so complex and what readers can do to simplify their
      lives while staying productive and balanced.

PMID- 11236196
TI  - A crash course in coaching.

PMID- 11236197
TI  - Expediency in proficiency testing.

PMID- 11236198
TI  - Dollar$ & $en$e. Part IV: Measuring the value of people, structural, and customer
      capital.
AB  - In Part I of this series, I introduced the concept of memes (1). Memes are ideas
      or concepts, the information world equivalent of genes. The goal of this series
      of articles is to infect you with my memes, so that you will assimilate,
      translate, and express them. We discovered that no matter what our area of
      expertise or "-ology," we all are in the information business. Our goal is to be
      in the wisdom business. We saw that when we convert raw data into wisdom we are
      moving along a value chain. Each step in the chain adds a different amount of
      value to the final product: timely, relevant, accurate, and precise knowledge
      which can then be applied to create the ultimate product in the value chain:
      wisdom. In Part II of this series, I infected you with a set of memes for
      measuring the cost of adding value (2). In Part III of this series, I infected
      you with a new set of memes for measuring the added value of knowledge, i.e.,
      intellectual capital (3). In Part IV of this series, I will infect you with memes
      for measuring the value of people, structural, and customer capital.

PMID- 11236199
TI  - The new, new thing: kappa vs. lambda.

PMID- 11236200
TI  - Successful strategies for negotiating RFPs and contracts.

PMID- 11236201
TI  - Purchased time off: an innovative retention tool?

PMID- 11236202
TI  - Refugee doctors. Long and winding road.

PMID- 11236203
TI  - NHS scrutiny. Here's looking at you, kid.
AB  - Bringing NHS organisations under the scrutiny of local government, as proposed by
      the NHS plan, will strengthen democratic monitoring. The proposed arrangements
      give an opportunity for greater integration of services. NHS organisations can
      gain from local authority experience in areas such as best value.

PMID- 11236204
TI  - Who wants to know?

PMID- 11236205
TI  - Building design. Suspended judgement.

PMID- 11236206
TI  - Answering your question on managing paperwork more effectively via improved
      filing procedures.

PMID- 11236207
TI  - Time management tune-up.

PMID- 11236208
TI  - The acquisition and maintenance of laboratory instrumentation.

PMID- 11236209
TI  - The instrument selection process: beyond the sales pitch.

PMID- 11236210
TI  - Therapeutic studies with a new combination benzoyl peroxide/clindamycin topical
      gel in acne vulgaris.
AB  - Three independent clinical studies were conducted in more than 1250 patients with
      moderate to moderately severe acne vulgaris to evaluate the efficacy and safety
      of a new combination gel that stably combines 5% benzoyl peroxide and 1%
      clindamycin. The results indicated that the benzoyl peroxide/clindamycin
      combination product was an effective treatment for reducing the inflammatory and
      noninflammatory lesions of acne vulgaris. In overall improvement as rated by the
      physicians and patients, the combination gel was superior to clindamycin alone,
      and in 2 of the 3 studies, to benzoyl peroxide alone. The antimicrobial activity
      of the combination gel was significantly (each P < .01) superior to that seen
      with topical application of its individual constituents, 5% benzoyl peroxide or
      1% clindamycin, and was numerically better than that found with topical
      application of a 5% benzoyl peroxide/3% erythromycin combination product. As with
      benzoyl peroxide, dry skin was the most frequent side effect with use of the
      combination gel, with isolated incidences of other localized irritation. No other
      safety or tolerability concerns were identified.

PMID- 11236211
TI  - The development of antibiotic resistance in Propionibacterium acnes.
AB  - Two separate studies evaluated the ability of a combination topical gel
      consisting of 5% benzoyl peroxide and 1% clindamycin to reduce facial
      Propionibacterium acnes counts in vivo and to decrease the development of
      resistant organisms. In the first study, the combination gel was compared with 3
      topical formulations of 1% clindamycin phosphate (gel, lotion, and solution) in
      80 individuals. After only 1 week of treatment, a 99.7% reduction from baseline
      in facial P acnes count was obtained with the combination gel. This was
      significantly greater (P < .001) than the 30%, 56%, or 62% reduction obtained
      with the clindamycin gel, lotion, or solution, respectively. After 2 weeks of
      treatment, the reduction from baseline P acnes counts with the combination gel
      was increased to 99.9%, which was again significantly greater (P < .001) than
      that with 1% clindamycin alone, regardless of the formulation. The second study
      compared the combination gel with 1% clindamycin gel in 79 patients with mild to
      moderate acne. After 4 weeks of treatment, the combination gel was more effective
      than clindamycin alone in reducing the total P acnes count, consistent with the
      previous study. By week 12, an increase in the number of resistant bacteria
      appeared in samples from patients using clindamycin alone, while counts of
      resistant bacteria remained stable or declined in those using the combination
      gel.

PMID- 11236212
TI  - Potential role for a new combination topical therapy in treating mild to moderate
      acne vulgaris.
AB  - Although a variety of established topical therapies are available to treat acne,
      treatment success is not always achieved with current preparations. Moreover,
      many patients find the formulations less than fully acceptable for various
      reasons. A new gel that stably combines 5% benzoyl peroxide and 1% clindamycin
      has become available to treat mild to moderately severe inflammatory acne. There
      are several benefits associated with this new topical combination product:
      cosmetic and aesthetic acceptability to patients; limited degradation of the
      antibiotic by the highly reactive benzoyl peroxide component when stored
      according to label instructions; less irritation and drying than alcohol-based
      preparations; and rapid onset of action, producing a bactericidal effect after
      just 1 week of twice-daily use and significant clinical improvements compared
      with clindamycin and vehicle gels within 2 weeks. Moreover, the decreased
      development of antibiotic-resistant strains of Propionibacterium acnes
      demonstrated with the combination gel may prolong treatment efficacy.

PMID- 11236213
TI  - Are 2 combined antimicrobial mechanisms better than 1 for the treatment of acne
      vulgaris? Clinical and antimicrobial results of a topical combination product
      containing 1% clindamycin and 5% benzoyl peroxide. Introduction.
AB  - Acne vulgaris is the most common chronic skin condition seen by dermatologists.
      Available topical therapies include comedolytic agents such as tretinoin,
      adapalene, azelaic acid, tazarotene, and salicylic acid; bactericidal agents such
      as benzoyl peroxide; antibiotics such as clindamycin, erythromycin, and
      tetracycline; and anti-inflammatory agents such as sodium sulfacetamide and
      metronidazole. Therapeutic failure with some antibiotic regimens due to the
      presence or development of resistant strains is becoming an increasing problem in
      the treatment of acne. One strategy aimed at limiting the resistant
      Propionibacterium acnes population is the use of treatment regimens that
      incorporate agents with complementary but different mechanisms of action. A
      combination gel consisting of 5% benzoyl peroxide and 1% clindamycin has recently
      become available. This supplement summarizes the dermatopharmacology, clinical
      efficacy, and tolerability of this combination gel, along with its potential role
      in the management of acne vulgaris.

PMID- 11236214
TI  - Dermatopharmacology of a new combination gel formulation for the topical
      treatment of acne.
AB  - A topical gel formulation has recently become available that stably combines 5%
      benzoyl peroxide and 1% clindamycin as phosphate, providing a convenient and
      effective multimodal therapy for acne vulgaris. A series of clinical
      investigations demonstrated that systemic exposure to clindamycin and degradation
      of clindamycin by the highly reactive benzoyl peroxide is minimal following a
      single application of the new formulation. Furthermore, the combination gel was
      similar to benzoyl peroxide in its irritation potential and ability to induce
      contact sensitization and has no phototoxic or photosensitization potential.

PMID- 11236215
TI  - Who has time to teach these days?

PMID- 11236216
TI  - Photo quiz. Contact nickel dermatitis.

PMID- 11236217
TI  - Successful treatment of generalized essential telangiectasia with the 585-nm
      flashlamp-pumped pulsed dye laser.
AB  - Generalized essential telangiectasia (GET) is a rare vascular condition with
      limited treatment options. We report the successful treatment of GET with the 585
      nm flashlamp-pumped pulsed dye laser (FLPDL).

PMID- 11236218
TI  - Eyelash hypertrichosis in a patient treated with topical latanoprost.
AB  - We describe a female patient with a history of primary open-angle glaucoma who,
      following treatment with topical latanoprost, a synthetic prostaglandin F2 alpha
      analog, developed hypertrichosis of the eyelashes. Hypertrichosis, a recently
      described side effect of latanoprost--together with iridal pigmentation-
      represents a potentially permanent cosmetic side effect associated with the use
      of this highly effective intraocular pressure-lowering agent. The molecular
      mechanism underlying latanoprost-induced hypertrichosis is unknown.

PMID- 11236219
TI  - What's eating you? Dermacentor andersoni.

PMID- 11236220
TI  - Testicular choriocarcinoma metastatic to the skin: an additional case and
      literature review.
AB  - Choriocarcinoma, a malignancy of trophoblastic cells, is characterized by the
      secretion of human chorionic gonadotropin (hCG). Choriocarcinoma primarily arises
      from the fetal (placental) trophoblasts in the setting of a molar pregnancy.
      Nongestational choriocarcinoma from the ovary or testis is much rarer. Testicular
      choriocarcinoma is a malignant tumor with great propensity for distant
      metastasis. The primary sites of metastasis are the lungs, liver, and brain. Skin
      metastasis is very rare but portends a grave prognosis when diagnosed. We present
      the case of a 24-year-old white male with a testicular mixed germ-cell tumor with
      skin metastases of choriocarcinoma.

PMID- 11236221
TI  - Congenital lacrimal sac fistula: a case report and review.
AB  - The lacrimal system is crucial for vision and comprises the lacrimal glands,
      which produce tears, and the lacrimal drainage system, which drains tears away
      from the eyes. While various disease processes affect the lacrimal glands, the
      lacrimal drainage system is commonly prone to congenital abnormalities such as
      lacrimal sac fistula. We describe a case with classic findings and review
      dermatologic manifestations of this entity.

PMID- 11236222
TI  - Cutaneous schwannoma of the foot.
AB  - Schwannomas usually present as solitary subcutaneous tumors adherent to a
      peripheral nerve. A solitary cutaneous schwannoma presenting as a solitary
      cutaneous nodule on the foot of a 19-year-old male is described. This is an
      unusual presentation of schwannoma. Saucerized excision produced an excellent
      result with no adverse effect on function or cutaneous sensation.

PMID- 11236223
TI  - Hypopigmented mycosis fungoides: a report of 7 cases and review of the
      literature.
AB  - Over the last 2 decades, hypopigmented macules have been reported with increasing
      frequency as an initial presentation of mycosis fungoides (MF). We
      retrospectively reviewed 7 patients with hypopigmented MF. The mean age was 35
      years at disease onset, with a mean of 5.5 years' duration of illness before
      presentation. All of our patients were Fitzpatrick skin type IV or V, and most
      reported pruritus. Histologic findings in all cases were consistent with MF.
      Treatment with topical nitrogen mustard produced repigmentation in 4 of 6
      patients.

PMID- 11236224
TI  - A center's callosities.
AB  - We present a case report of a 14-year-old white male who developed hyperkeratotic
      plaques on the distal aspects of 2 toes. He was referred by his primary care
      physician for the treatment of onychomycosis. With questioning, the patient
      stated that he played center for his high school basketball team. After physical
      examination, he was diagnosed with callosities caused by his basketball
      activities. Proper nail hygiene and wearing of larger footwear resulted in
      improvement of his callosities. Sports-related cutaneous injuries should be
      included in the differential diagnosis of nail and toe abnormalities.

PMID- 11236225
TI  - Acral purpuric plaques in a woman with asthma: a case of allergic granulomatosis
      angiitis.
AB  - Allergic granulomatosis angiitis (AGA) is a rare systemic vasculitis of unknown
      etiology. Most patients are adults in their third to fourth decade of life. The
      combination of asthma, eosinophilia, and necrotizing vasculitis is almost
      invariably present. Cutaneous lesions are found in up to 70% of the patients and
      include nodules, hemorrhagic lesions, and erythema multiformelike lesions. We
      provide a case report of a 30-year-old woman with asthma who presented with acral
      purpuric plaques and was diagnosed with AGA.

PMID- 11236226
TI  - Polypoid clear cell acanthoma of the scalp.
AB  - Clear cell acanthoma (CCA) is a rare, benign epithelial tumor most frequently
      found on the lower extremities. Its clinical appearance may vary considerably,
      and cases of multiple lesions have been reported. The diagnosis is made by
      viewing the characteristic histologic features. This case describes an unusual
      scalp lesion that clinically and histologically shows unique polypoid features.

PMID- 11236227
TI  - Necrobiosis lipoidica associated with Kobner's phenomenon in a patient with
      diabetes.
AB  - Necrobiosis lipoidica (NL) is a granulomatous disease that usually presents on
      the lower extremities of patients with diabetes mellitus. We present a rare case
      of NL kobnerizing in a surgical scar on the upper extremity of a patient with
      diabetes. NL is generally refractory to treatment.

PMID- 11236228
TI  - Lipodystrophy.
AB  - Congenital lipodystrophy is an uncommon autosomal recessive disorder that occurs
      mainly in females and is characterized by loss of subcutaneous fat, insulin
      dependent diabetes mellitus, and masculinization due to defective metabolism of
      fat. Acquired lipodystrophy is now most commonly encountered in patients infected
      with HIV who take protease inhibitors. We present an illustrative case of
      lipodystrophy and review the presenting signs allowing for an accurate clinical
      diagnosis.

PMID- 11236229
TI  - A combination benzoyl peroxide and clindamycin topical gel compared with benzoyl
      peroxide, clindamycin phosphate, and vehicle in the treatment of acne vulgaris.
AB  - A topical gel combining 5% benzoyl peroxide and 1% clindamycin as phosphate was
      evaluated in a 10-week randomized double-blind trial involving 287 patients with
      moderate to moderately severe acne. The combination agent demonstrated
      significantly greater reductions in inflammatory lesions than either of its
      active constituents (5% benzoyl peroxide and 1% clindamycin) or vehicle when used
      alone. Significantly greater reductions in comedos and improvements, as measured
      by both physicians' and patients' global evaluations, were obtained with the
      combination agent than with clindamycin or vehicle. The reduction in comedos and
      the global improvements were similar between the combination agent and benzoyl
      peroxide. The combination agent was well tolerated; the incidence of dry skin was
      similar to that found with benzoyl peroxide, and other adverse events were
      similar to that with vehicle. The improved efficacy obtained with combination
      therapy was accompanied by a safety profile similar to that of either constituent
      used alone.

PMID- 11236230
TI  - Use of Medicaid 1915(c) home- and community-based care waivers to reconfigure
      state long-term care systems.
AB  - Since Congressional authorization in 1981, Medicaid 1915(c) home- and community
      based care waivers have influenced states' efforts to transform their long-term
      care systems. In 1997, every state participated in the 1915(c) waiver program,
      while waiver expenditures, at $8.1 billion, represented 59.6 percent of all
      Medicaid community-based care expenditures. To explore state-level factors that
      appear related to these expenditures, the authors turn to a body of work on
      Medicaid resource allocation. They compare the influence of five factors-
      sociodemographic, supply, economic, programmatic, and political environment--on
      states' allocations to long-term care expenditures and 1915(c) waiver
      expenditures. The state economic environment was an important influence on total,
      as well as waiver expenditures. State regulation of long-term care supply
      demonstrated the most substantive relationship, increasing the share of dollars
      supporting 1915(c) waivers from 11.6 to 20.0 over the study period, all else
      equal.

PMID- 11236231
TI  - The impact of the Medicaid expansions for pregnant women: a synthesis of the
      evidence.
AB  - This article provides a comprehensive review of the published literature on the
      impact of expanding Medicaid for pregnant women to higher income groups of women.
      The major expansions took place between April 1987 and July 1989. These studies
      show evidence that new groups of pregnant women received health insurance
      coverage through Medicaid, and that some women received improved prenatal care
      services. The evidence is much weaker that the expansions led to improved birth
      outcomes. The fact that other parts of the developed world have experienced
      sustained declines in infant mortality without expansions of health insurance
      coverage points to the complexity in the origins of poor birth outcomes. It is
      possible that the benefits from the Medicaid expansions were merely victories in
      small battles within a much larger war that remains to be won.

PMID- 11236232
TI  - The impact of state policy on the costs of HIV infection.
AB  - There is substantial variation in the generosity of public assistance programs
      that affect HIV+ patients, and these differences should affect the economic
      outcomes associated with HIV infection. This article uses data from a nationally
      representative sample of HIV+ patients to assess how differences across states in
      Medicaid and AIDS Drug Assistance Programs (ADAP) affect costs and labor market
      outcomes for HIV+ patients in care in that state. Making ADAP programs more
      generous in terms of drug coverage would reduce per patient total monthly costs,
      mainly through a reduction in hospitalization costs. In contrast, expanding ADAP
      eligibility by increasing the income threshold would increase the total cost of
      care. Expanding eligibility for Medicaid through the medically needy program
      would increase per patient total costs, but full-time employment would increase
      and so would monthly earnings. The authors conclude that more generous state
      policies toward HIV+ patients--especially those designed to provide access to
      efficacious treatment--could improve the economic outcomes associated with HIV.

PMID- 11236234
TI  - Ownership type and community benefits of women's health centers.
AB  - An important aspect of the changing health care system is the growth of women's
      health centers--organizations that design and deliver services to women. This
      growth has generated interest in the behavior of centers, especially because of
      increasing awareness of women's health issues. Using data from the 1994 National
      Survey of Women's Health Centers, the authors examined the association between
      ownership of centers and 12 measures of community benefits, and 296 nonprofit and
      108 for-profit centers were compared. Overall, the nonprofits performed better
      than the for-profits in terms of serving underserved women, delivering
      comprehensive primary care services, providing training for health professionals
      and education services for clients and the community, and involving the community
      in center governance. Among women's health centers, the results show that
      ownership matters, and indicate the importance of supporting providers who serve
      the underserved and developing a standard of community benefits.

PMID- 11236233
TI  - Provider choice and utility loss due to selective contracting in rural and urban
      areas.
AB  - An econometric model estimated the disutility of traveling long distances for
      depression treatment, and simulations calculated the utility loss associated with
      selective contracting in rural and urban areas. A representative sample of
      depression patients (n = 106) and all practicing providers (n = 3,710) in
      Arkansas were identified and the distances between them were calculated. Using
      discrete choice analysis, patient preferences for provider type and travel
      distance were estimated. Simulations calculated the utility loss associated with
      alternative scenarios of selective contracting. Provider type and distance were
      significant predictors of provider choice. To equate the utility loss associated
      with selective contracting in rural and urban areas, a slightly higher proportion
      of rural physicians and a substantially higher proportion of rural mental health
      specialists must be contracted. To avoid further reductions in geographic access,
      managed care organizations should contract with a higher proportion of rural
      providers than urban providers.

PMID- 11236235
TI  - Separating the men from the boys: masculinity, psychosexual development, and sex
      crime in the United States, 1930s-1960s.

PMID- 11236236
TI  - Dangerous minds: changing psychiatric views of the mentally ill in Porfirian
      Mexico, 1876-1911.

PMID- 11236237
TI  - The mysterious history of partridge poisoning.

PMID- 11236238
TI  - [The effect of treatment with enalapril versus losartan on levels of insulin
      resistance in patients with essential hypertension].
AB  - Insulin resistance and hyperinsulinaemia are presumed to participate in the
      pathogenesis of essential hypertension (EH). Insulin resistance is characterised
      by an impaired insulin-mediated glucose uptake. Participation of the renin
      angiotensin system in the development of hyperinsulinaemia in EH patients has not
      been unanimously proven. The present study aimed to asses the influence of
      antihypertensive therapy with angiotensin converting enzyme inhibitor (ACEI,
      enalapril = 10 mg/day) (9 male patients) or angiotensin II AT-1 receptor blocker
      (A II RB = losartan 50 mg/day) (9 male patients) respectively on insulin
      sensitivity in patients with EH. 3-hours euglycaemic clamp test with constant
      infusion of insulin (50 mU/m2/min) was performed twice: before and after 8 weeks
      of therapy with ACEI or A II RB respectively. The control group (CG) consisted of
      12 healthy males (clamp test was performed once). Serum insulin concentration (I)
      was estimated by radioimmunoassay. Glucose disposal rate (M-value = mg/kg/min)
      and tissue insulin sensitivity (M/I value = mg/kg/min per mU/l) were calculated
      in subjects of the CG and in patients with EH before and after antihypertensive
      therapy with ACEI or A II RB, respectively. In CG the M-value (7.38 +/- 0.13) and
      tissue insulin sensitivity (M/I = = 6.76 +/- 0.19) were significantly higher than
      in EH before treatment with ACEI (M-value = 5.44 +/- 0.16; M/I = = 4.57 +/- 0.18)
      or A II RB (M-value = 5.75 +/- 0.21; M/I = 4.77 +/- 0.31), respectively. ACEI
      therapy was followed by a significant increase of both M (6.82 +/- 0.25) and M/I
      (5.68 +/- 0.25) values. In contrast to ACEI, treatment with A II RB did not
      influence neither M (5.75 +/- 0.21) nor M/I (4.79 +/- 0.21) values respectively.
      In contrast to A II RB, ACEI shows a beneficial effect on insulin sensitivity in
      EH patients. This effect does not seem to be mediated by an influence on the AT-1
      receptor.

PMID- 11236239
TI  - [Relationship between results of electrocardiographic exercise tests and
      intraesophageal pH in men with atypical chest pain].
AB  - Changes in intraesophageal pH can influence myocardium perfusion via neural
      reflexes. The aim of this study was to estimate the relationships between
      intraesophageal pH and the course of electrocardiographic exercise test. 38 male
      patients with atypical chest pain in mean age 41.1 +/- 7.8 years were studied. In
      all among other 24-hours oesophageal pH monitoring and exercise test on running
      track with simultaneous oesophageal pH monitoring were made. Pathological acid
      reflux in 24-hours monitoring had 11 (29%) patients, exertional acid
      gastroesophageal reflux in 8 (21%) patients was found and significant ST interval
      depression in ecg in 11 (29%) patients was observed. The differences in patients
      quantity in respective subgroups were not significant. Patients with significant
      ST interval depression during exercise test, in comparison with patients without
      significant ecg changes, had lower HDL cholesterol level and higher values of
      daily and exertional gastroesophageal acid reflux parameters. Multiple-regression
      analysis showed that indicators of functional (pH-metry) and morphological
      (endoscopy and histology) oesophageal status were the independent factors
      determining variance of: exercise test duration, percentage of maximal heart rate
      during exercise test, double product value and maximal ST interval depression. In
      conclusion, changes in intraesophageal pH can influence exercise test course.

PMID- 11236240
TI  - [Chronic peripheral arterial occlusive disease, platelet glycoproteins GPIIb-IIIa
      and GP Ib-IX, plasma von Willebrand factor and plasma fibrinogen concentrations
      in patients with type 2 diabetes mellitus].
AB  - Diabetes mellitus (DM) type 2 is a very strong risk factor for atherosclerosis.
      The final event of atherosclerosis is the vessels occlusion by platelet riche
      thrombus. Platelets adhesion and aggregation is mediated by interaction between
      platelets glycoproteins: GPIb-IX, GPIIb-IIIa and adhesive proteins: von
      Willebrand factor or fibrinogen. The expression of platelets GPIb-IX, GPIIb-IIIa,
      plasma vWF, fibrinogen concentrations were evaluated in 40 patients with diabetes
      type 2 (22 patients with PAOD stage II and IV according to Fontain, 18 diabetics
      without paod) and 32 healthy individuals. The expression of platelets
      glycoproteins GPIIb-IIIa and GPIb-IX was estimated by ELISA using monoclonal
      antibody against GPIIb-IIIa (CD41a) and GPIb-IX (CD 42a Immunotech). Plasma vWf
      (189.7 +/- 53.6%), fibrinogen (4.5 +/- +/- 1.3 g/l) level and expression of
      platelets GPIb-IX (63.2 +/- 19.6% in platelets concentration 125,000/mm3, 104.5
      +/- 28.1% in platelets concentrations 250,000/mm3) and GPIIb-IIIa 50.8 +/- 10.1%
      in platelets concentrations 125,000/mm3, 95.3 +/- 21.3% in platelets
      concentrations 250,000/mm3 were statistically higher in patients with diabetes
      type 2 than in controls (vWf: 94.9 +/- 27.1%, fibrinogen: 2.8 +/- 0.4 g/l, GPIb
      IX in platelets concentration 125,000/mm3: 43.8 +/- 9.3%, in concentration
      250,000/mm3: 83.9 +/- 18.3%, GPIIb-IIIa in platelets concentration 125,000/mm3:
      33.7 +/- 10.1%, in platelets concentration 250,000/mm3: 63.2 +/- 15.4%). We found
      significant correlation between the expression of GPIIb-IIIa, GPIb-IIIa, GPIb-IX
      and plasma adhesive proteins: vWF, fibrinogen in controls and both subgroups of
      diabetic patients. The correlation between plasma vWF and fibrinogen level and
      degree of arterial insufficiency in diabetic patients was also found. We can
      assume that higher vWf, fibrinogen plasma level in diabetic patients with and
      without PAOD could account for high expression of platelets GPIIb-IIIa and GPIb
      IX.

PMID- 11236241
TI  - [The prognostic value of electrocardiographic exercise test in patients after
      acute myocardial infarction].
AB  - The subject of this trial were 243 patients with uncomplicated acute myocardial
      infarction, hospitalized in years 1992-1996, who were made an
      electrocardiographic exercise test in the second or third week of the in-hospital
      stay and whose further history in the 2-6 period after myocardial infarction
      (average follow-up time lasted for 4.0 +/- 1.9 years) was known. The aim of this
      trial was to determine the influence of the positive exercise test on the long
      term prognosis after acute myocardial infarction in a group with uncomplicated
      acute myocardial infarction. The course of infarction and the frequency of
      cardiac events (cardiac death, reinfarction, revascularisation) occurrence in 78
      patients with positive exercise test (group I) were compared with a group of 165
      patients with negative exercise test (group II). Both groups were compared in
      respect to age, gender, history of myocardial infarction, risk factors and the
      course of the infarction in the in-hospital period. The multivariable logistic
      regression analyse showed that the positive exercise test did not have a
      statistically significant influence on the increase of post-hospital morbidity
      but it correlates with significantly more frequent use of the invasive treatment
      and reinfarction during the follow-up period in this group. Negative exercise
      test in patients with uncomplicated acute myocardial was a significant factor of
      the good long-term prognosis.

PMID- 11236243
TI  - [Granulocyte colony stimulating factor (G-CSF) in diagnosis and monitoring of non
      small-cell lung cancer (NSCLC)].
AB  - Granulocyte-colony stimulating factor (G-CSF) is one of the glycoproteins called
      colony-stimulating factors (CSFs). It has been shown that the target of the
      actions of CSFs are not limited to hematopoietic cells but can also affect the
      proliferation of nonhematopoietic cells. Some clinical investigations have shown
      the presence of cell surface receptors for G-CSF in lung cancer cells and
      autologous production of G-CSF in various human cell lines derived from non-small
      cell lung cancer (NSCLC). The purpose of this investigation was to compare serum
      levels of G-CSF in NSCLC patients to a control group, to assess pre- and post
      treatment levels of G-CSF in relation to levels of commonly accepted tumour
      markers such as carcinoembryonic antigen (CEA) and cytokeratin fragment 19 (CYFRA
      21-1), and to define the sensitivity of G-CSF in NSCLC. In this study, the serum
      levels of tumour markers were measured in 34 patients with NSCLC and in 20
      healthy subjects. Serum samples were drawn before surgery and 10, 30, 90, 180 and
      270 days after surgery. G-CSF and CEA were assayed using ELISA system and CYFRA
      21-1 was measured by radioimmunoassay (RIA). Preoperative level of G-CSF was
      significantly increased in cancer patients relative to the control group.
      Concentrations of G-CSF and CYFRA 21-1 were decreased on the 10th day, but CEA on
      the 30th day after operation. The diagnostic sensitivity of G-CSF was 66%, CEA-
      62% and CYFRA 21-1--51%. Combined use of two markers increased the sensitivity in
      comparison to the use of G-CSF only. These results suggest that G-CSF may be
      useful in diagnostic and monitoring of NSCLC, but they need further studies.

PMID- 11236242
TI  - [Glucose tolerance, function of pancreatic B-cells and blood lipids in "healthy"
      offspring of parents with conjugal type 2 diabetes].
AB  - In 56 adult normoglycemic nondiabetic (WHO criteria) subjects, whose both parents
      had type 2 diabetes, and in 68 control probants, matched for age, sex and body
      mass without family history of diabetes, the OGTT (75 g) was carried out,
      including measurement of serum insulin (IRI) and C-peptide (CP). In fasting state
      also the blood lipid profile was determined: serum triglycerides, total
      cholesterol, LDL-cholesterol, HDL-cholesterol, apolipoprotein AI (apoAI) and
      apolipoprotein B (apoB). In comparison with the control group, the offspring had
      significantly lower mean glycaemia on fasting, and non significantly elevated
      from the 60 min of the test, the significantly higher values of serum IRI and CP
      in fasting state and at the end of the test (120-180 min), and significantly
      lower serum CP:IRI molar ratio, expressing the reduced hepatic clearance of
      insulin. The offspring had significantly higher mean values of serum LDL
      cholesterol, and significantly lower of serum HDL-cholesterol and apoAI, not
      disclosing significant differences in the serum levels of triglycerides, total
      cholesterol and apoB with the control group. Only serum HDL-cholesterol was
      significantly (negatively) correlated wit serum IRI and CP-values. The covariance
      analysis, eliminating the influence of age, body mass and the secretory activity
      of pancreatic B-cells, revealed the significant correlation of the presence of
      parental diabetes with serum levels of LDL-cholesterol (increase), and HDL
      cholesterol and apoAI (decrease) in the offspring. These results prove
      indirectly, that in subjects genetically predisposed to type 2 diabetes, before
      the manifestation of glucose intolerance are present other effects of insulin
      resistance, expressed in increased activity of pancreatic B-cells, increased
      transfer of insulin to extrahepatic tissues, and in changes of
      concentration/composition of some lipoproteins dues to reduced influence of
      insulin on the enzymes which control their metabolism.

PMID- 11236244
TI  - [The effect of hemodialysis on the virgin CD45RA+, CD45RO- and memory CD45RO+,
      CD45RA- lymphocyte count in patients with chronic renal failure].
AB  - The hallmark of immunological memory is a quick and effective response to a
      repeated antigen exposure. Virgin lymphocytes, with their surface receptors
      CD45RA+, CD45RO- are produced in primary lymphatic organs, then migrating to
      secondary lymphatic structures. Memory lymphocytes CD45RO+, CD45RA- produced in
      these organs migrate to non-lymphatic organs--a possible location of inflammatory
      process, thus enabling the immunological system to eliminate effectively the same
      antigen, when repeatedly present. The aim of the study was 1) to test the
      influence of hemodialysis on the number of virgin lymphocytes and/or memory
      lymphocytes; 2) whether such impact (if any) depends on the type of dialysis
      membrane used (cuprophan or polysulphon), 3) if the effect is different in
      patients with or without diabetes. Overall number of virgin T helper lymphocytes
      CD45RA+CD4+ was significantly lower in patients with end-stage renal disease,
      while the number of total CD45RO+, CD45RA- memory lymphocytes was significantly
      greater among patients with diabetic nephropathy, compared to normal control
      subjects. After 15 minutes of hemodialysis, number of virgin lymphocytes CD45RA+,
      CD45RO- (p < 0.001, p < 0.01) and their subclasses, as well as memory lymphocytes
      CD45RO+, CD45RA- were significantly decreased. After 15 minutes of hemodialysis
      with polysulphon membrane, the decrease in T virgin cytotoxic, B virgin
      CD45RA+CD4-, T memory cytotoxic as well as B memory CD45RO+CD4- lymphocytes was
      significantly lower, when compared with cuprophan membrane (p < 0.02). Among
      patients treated with cuprophan hemodialysis, the decrease of T helper memory
      CD45RO+CD4+ lymphocytes was significantly lower in patients with diabetic
      nephropathy, than in non-diabetic patients. CONCLUSIONS: In all patients with end
      stage renal disease, the impact of hemodialysis on the number of memory
      lymphocytes CD45RO+, CD45RA-, as well as virgin lymphocytes CD45RA+, CD45RO- was
      shown, but the effect was less profound during hemodialysis with polysulphon
      membrane, compared to cuprophan. The presence of diabetic nephropathy effects the
      hemodialysis-induced changes in the number of T memory helper CD45RO+ CD45RO+CD4+
      lymphocytes, with no impact on other subclasses of the examined cells.

PMID- 11236245
TI  - [Treatment of essential thrombocythemia--personal experience].
AB  - The present paper summarizes 13-years our center's experience in the treatment of
      essential thrombocythemia (ET). We analyzed a group of 36 patients treated with
      busulphan (Bu), 16 with hydroxyurea (HU) and 4 with interferon alpha (INF alpha).
      The results of therapy were assessed using proposed self-defined criteria of ET
      remission. The remission of ET was achieved in 75% of the patients treated with
      Bu and 57% treated with HU followed for at least 2 years. In the INF alpha
      treated group cytoreduction was achieved only in patients in whom initial dose of
      INF alpha was 6 mln I.U. per day. HU seems to be the drug of choice in younger
      patients because of possible mutagenic effect of Bu as well as in those, in whom
      Bu was administered in high total dose. During the cytoreductive or maintenance
      therapy with HU the blood morphology should be often controlled because of
      relatively high frequency (40%) of leukopenia. In each case of ET cytogenetic
      examination is necessary. Ph-positive ET determine the choice of the treatment.

PMID- 11236246
TI  - [The effect of smoking tobacco and drinking of alcohol and coffee on bone mineral
      density of healthy men 40 years of age].
AB  - The aim of the study was to evaluate the effects of smoking, alcohol and coffee
      drinking on bone mineral content (BMC) in a group of 258 healthy men, aged 40-63,
      occupationally active inhabitants of Wroclaw. Trabecular, cortical and total BMC
      at the distal radius of the non-dominant hand were measured by pQCT method using
      the Stratec apparatus. The data concerning smoking, alcohol and coffee intake
      were obtained through a questionnaire. The significance of BMC differences
      between groups were tested using a one-way analysis of variance ANOVA. The extent
      of alcohol intake did not differentiate BMC values at the distal radius, whereas
      the significant detrimental effects of both smoking and coffee drinking on
      trabecular (but not cortical and total) BMC were revealed. Among healthy Polish
      males coffee drinking was associated with a significant reduction of trabecular
      BMC. Simultaneously, smokers and ex-smokers (when compared to never-smokers) had
      lower trabecular BMC.

PMID- 11236248
TI  - [Ischemic ulcer in Madelung disease].
AB  - We describe a 50 years old man with multiple symmetric lipomatosis (Madelung
      disease) and two years history of intermittent claudication who was hospitalized
      because of persistent ulcer of left foot. Lipomata were located on the neck,
      shoulders and chest; they enlarged gradually over a few years, becoming huge in
      size. Ulceration of the foot appeared a few weeks before hospitalization and its
      ischaemic origin was uncertain because of atypical character (painless,
      ankle/brachial index > 0.5). After angiographic examination patient was assigned
      for conservative treatment. Intravenous infusions of alprostadil were given with
      poor effect. Because of gradual enlargement of the ulceration, pain
      intensification and relatively favourable angiographic picture aorto-bifemoral
      prosthesis implantation was performed with satisfactory short-therm effect. In
      addition, patient required vitamin B12 supplementation due to megalocytic anemia.

PMID- 11236247
TI  - [A case of rapidly progressive glomerulonephritis in the course of Wegener's
      granulomatosis].
AB  - Wegener's granulomatosis (WG) is characterized by granulomatous vasculitis of the
      respiratory tract and glomerulonephritis (GN). Prognosis of this disease is poor
      and about 20% of untreated patients die after one year from the onset. WG was
      recognized in 45-year-old patient on the basis of: 1) clinical symptoms (joint
      pain and swollen, purpura on the skin which appeared one week after respiratory
      tract infection, ulceration of the tonsils and lingula), 2) results of additional
      testing (X-chest-ray-infiltrates of both lungs), positive results of the cANCA
      (titre 1:640) and rapidly progressive renal failure [the increase of serum
      creatinine level (Pcr) from 123.7 to 707 mumol/l (1.4 to 8.0 mg/dl) during one
      week]. Renal biopsy revealed extracapillary GN (cellular crescents in 7 out of 8
      glomeruli and scattered foci of fibrinoid necrosis of capillary walls in all). At
      the beginning of the treatment Pcr raised to 884 mumol/l (10 mg/dl) and the
      patient required hemodialysis. He was treated with methylprednisolone (M) at
      flash doses of 1000 mg/24 h by three days followed by 125 mg/24 h i.v.--because
      of peptic ulcer, with cyclophosphamide (C-150 mg/24 h p.p.), with
      trimetoprim/sulphametoxazole, with pentoxifylline and omeprazol. After six weeks
      of the treatment in the control kidney biopsy sclerotic changes in 10 out of 13
      glomeruli and diffuse interstitial fibrosis were found. However, during the same
      time, we observed clinical remission of the disease and the decrease of Pcr to
      176.8 mumol/l (2 mg/dl). The M dosis was reduced by 5 mg every weeks and the C
      dosis--to 50 mg (because of the increase of aminotransferase levels) After six
      months of the treatment Pcr was 132.6 mumol/l (1.5 mg/dl) and CANCA titer was
      1:16. In this case of RPGN, despite off the progression of the morphological
      changes in the kidney, we obtained the clinical remission of the disease and
      significant decrease of Pcr level. These results suggest that aggressive
      treatment of WG is justified even in patients with advanced renal failure
      requiring dialysis and in such patients clinical remission is possible to occur.

PMID- 11236249
TI  - [Unusual cases of non-Hodgkin's lymphomas--case reports].
AB  - We describe 4 cases of non-Hodkin's lymphomas that were interesting because of
      their curiosal clinical courses and spontaneous complete remissions during the
      course of high malignancy lymphoma. We present three of them for the first time
      in Poland. Case 1: a 61-year old woman was admitted to the hospital because of
      the headache, lasting for 4 months before hospitalization and right hemiparesis.
      CT scans revealed the presence of tumor in the temporo-occipital region. The
      diagnosis of B-cell lymphoma was established at histopathological examination of
      the postoperative material. Co60--therapy of these region was applied after the
      operation with good response. Case 2: a 38-year woman was admitted to the
      hospital because of L5-S1 spondylolisthesis to operate it. During the
      hospitalization haemolytic anaemia of unknown origin, thrombocytopoenia,
      splenomegaly, fever and rising acute insufficiency of kidneys, heart, liver and
      CNS were occurred. The patient died, despite applying corticosteroidotherapy. The
      diagnosis of intravascular lymphoma was established at postmortem examination.
      Case 3: a 51-year old woman was admitted to the hospital with diagnosis:
      anaplastic non-Hodgkin lymphoma B-cell type high malignancy established after the
      double histopathological examination of lymph nodes and biopsy of the lung. At
      the admission to the Department of Haematology we stated absolute regression of
      these changes. The patient had been only observed in the Outpatient Department
      over 1 year. She died after 6 months since the beginning of the relapse despite
      intensive chemotherapy. Case 4: a 43-year old man was admitted to the hospital
      because of great hyperleukocytosis, hepatosplenomegaly and neurological symptoms.
      The diagnosis: chronic prolymphocytic leukaemia was established. The
      cerebrospinal fluid examination showed presence of mononuclears which infiltrated
      CNS. CT scans of the brain revealed leucaemic infiltrations of the hemispheres
      and cerebellum. The patient died despite intensive therapy due to rising
      progressive multiorgan failure.

PMID- 11236250
TI  - [Use of transdermal fentanyl for treatment of chronic pain].

PMID- 11236251
TI  - [Use of melatonin as an adjuvant treatment for neoplasms].

PMID- 11236252
TI  - [Health status and cause of death for Jan Kasprowicz].

PMID- 11236253
TI  - [The role of the immune system in the pathogenesis of hypertension].

PMID- 11236254
TI  - [Cytogenetic changes in Ph(+) chronic granulocytic leukemia under the influence
      of interferon alpha (IFN-alpha) therapy].
AB  - Chromosomal changes during therapy with IFN-alpha were analysed in 21 patients
      suffering of chronic granulocytic leukemia. Complete or major cytogenetic
      response (CgR) was obtained in 4 patients, minor in 5 minimal in 7, and no
      response in 5 patients. Patients showing a low Sokal index more often disclosed
      CgR. In 6 persons additional chromosomal aberrations were present at diagnosis or
      during the disease course. They disappeared on IFN-alpha therapy. This fact may
      be in favour of the influence of IFN-alpha not only on disappearance of Ph
      chromosome, but also of secondary aberrations, some of them indicating the
      possibility of an acceleration of the disease. No relation of the CgR, as well as
      Sokal index value to the survival time in presented small cohort could be
      observed, which may depend on short observation time. CgR did not depend on a
      type of fusion of BCR/ABL gene. However, survival time was longer in patients
      with b3a2 fusion.

PMID- 11236256
TI  - [Use of harmonic echocardiographic contrast imaging and intravenous bolus of
      Levovist for evaluation of the left ventricle].
AB  - Harmonic imaging is a new imaging modality using nonlinear acoustic response,
      which is particularly sensitive for the particles of contrast agents. Our study
      was designed to compare the potential of harmonic echocardiographic imaging of
      the left ventricle using a contrast agent, Levovist to improve the detection of
      endocardium in patients with suboptimal image quality. 40 patients were studied
      using standard transthoracic apical views of the left ventricle patients using
      fundamental frequency and second harmonic frequency after and intravenous
      injection of 2.5 g Levovist. The quality of endocardial delineation in 16
      standard segments was scored from 0 to 2. Endocardial visualization index was
      calculated as a mean of the scores to express overall diagnostic quality.
      Harmonic imaging with contrast significantly improved left ventricular
      endocardial border detection (endocardial visualization index at baseline 1.24 +/
      0.41, with contrast 1.63 +/- 0.38; p < 0.001). The improvement was qualitatively
      observed in all parts of the left ventricle: in apex (2.4 +/- 0.8), in the middle
      part (2.5 +/- 0.9) and slightly less in the basal part (2.1 +/- 1.1) as scored on
      a 0-3 scale. The number of invisible segments decreased from 124 (fundamental) to
      50 in contrast harmonic mode. The persistence of the contrast enhancement,
      prolonged in harmonic as compared to fundamental imaging (284 +/- 136s vs 117 +/-
      87s; p < 0.001) enabled convenient recording of all necessary views. Harmonic
      imaging after an intravenous injection of Levovist significantly improves the
      visualization of left ventricular endocardial border. Prolonged contrast effect
      after a single bolus enhances the pertinence of the method in clinical practice.

PMID- 11236255
TI  - [Neurohumoral factors in hypertensive patients with and without left ventricular
      hypertrophy].
AB  - Increased pressure load and neurohumoral activation are main factors involved in
      pathomechanism of left ventricular hypertrophy (LVH) in hypertension (HT). To
      gain insight into the involvement of neurohumoral factors responsible for cardiac
      hypertrophy, plasma level of aldosterone (Aldo), plasma renin activity (PRA),
      insulin-like growth factor-1 (IGF-1), pro-endothelin-1 (pro-ET) and atrial
      natriuretic peptide (ANP) were measured in HT patients (pts) and compared between
      pts with and without LVH. Also relationships between neurohormones and LV mass
      index (LVMI), mean blood pressure (MBP) were assessed separately in HT pts with
      and without LVH. 121 HT patients (pts) of age 17-79 (mean 48 +/- 15.3) were
      divided into three groups: 1-53 pts with mild HT, 2-44 pts with moderate HT and 3
      24 pts with severe HT. Each of the group was divided into pts with and without
      LVH further all HT pts were divided into two groups; with and without LVH.
      Control group consisted of 39 healthy normotensives. LV mass was assessed
      echocardiographically and plasma levels of IGF-1, PRA, Aldo, pro-ET, and ANP were
      measured by radioimmunoassay in each pts and controls. LVH was found in 35.8% pts
      with mild HT, in 68.18% pts with moderate HT and in 100% pts with severe HT. The
      level of all measured neurohormones were significantly higher in pts with LVH
      compared to pts without LVH (p < 0.001). In pts with LVH there was significant
      correlation between LVMI and IGF-1, PRA, Aldo, pro-ET-1 and ANP, contrary to pts
      without LVH in which such correlations was not found. In pts with LVH there was
      also significant correlation between MBP and IGF-1, PRA, ANP and pro-ET-1.
      Increased plasma level of PRA, Aldo, IGF-1, pro-ET-1 and ANP in HT pts with LVH
      and significant correlation between measured neurohormones and LVMI suggests
      their contribution to LVH in HT pts. Significant correlation between LVMI, MBP
      and IGF-1 level, PRA and ANP indicate interplay between hemodynamic and
      neuroendocrine factors in pathomechanism of LVH.

PMID- 11236257
TI  - [Dispersion of the QT interval in unstable angina pectoris].
AB  - Increased dispersion of the QT interval is a risk factor of sudden cardiac death.
      In unstable angina pectoris (UA) a few authors described QT dispersion. The aim
      of the study was to assess QT dispersion in patients with UA in comparison to the
      healthy subjects and analysis QT dispersion according to the presence during in
      hospital stay significant cardiac events like: death due to cardiological causes,
      myocardial infarction and urgent revascularization. Study group consisted of 54
      patients with UA in a class IIIB of Braunwald classification (18 women, 36 men,
      mean age: 58.2 +/- 9.6 years). In 40 patients after pharmacological treatment
      stabilization in the first three days of hospitalization was achieved and during
      in-hospital stay significant cardiac events were not observed--group I. In 14
      patients during in-hospital stay significant cardiac events were present,
      including 5 death due to cardiological causes--group II. During first two days of
      hospitalization coronary angiography was performed in all patients. The control
      group comprised 25 healthy subjects (8 women, 17 men, mean age 56.4 +/- 6.1
      years). On admission to the hospital in all patients and in control group, using
      standard 12-leads ECG, following parameters were calculated: QT dispersion (QTd),
      corrected QT dispersion based on Bazett's formula (QTcd) and QT dispersion ratio
      (QTdR). In the study group as well as in group I and II values of QTd, QTcd and
      QTdR were significantly higher than in healthy subjects. In group I all the QT
      parameters were significantly lower than in group II (QTd: 56.8 +/- 11.2 vs 68.6
      +/- 16.6 ms, p = 0.002). The highest value of QT dispersion was found in patients
      who died during in-hospital stay and it was significantly higher than in
      survivors (86.0 +/- 13.4 vs 57.1 +/- +/- 10.6 ms, p = 0.004). A cut-off value for
      QTdR > or = 9% identified patients with high risk of sudden cardiac death.
      CONCLUSIONS: QT dispersion analysis in unstable angina pectoris allows to
      distinguish patients according to the risk of sudden cardiac death. Patients with
      high risk of sudden cardiac death identify the best QTdR.

PMID- 11236258
TI  - [Blood coagulation activation in patients with ulcerative colitis].
AB  - Hemostasis disturbances in patients with ulcerative colitis (uc) can result from
      quantity and quality changes in blood coagulation factors synthesis (acute phase
      reaction) as well as their consumption in inflammatory processes affecting in
      large bowel. The aim of this study was to estimate a coagulation system
      activation in patients with uc. PATIENTS AND METHODS: 42 patients with uc, 21 in
      active and 21 in inactive disease phase as well as 26 healthy persons were
      studied. In all concentration of thrombin-antithrombin III complexes (TAT),
      antithrombin III and prekallikrein activities, von Willebrand factor (vWf) and
      fibrinogen concentrations, kaolin-kephalin time (aPTT), prothrombin level and
      platelets count were determined. RESULTS: In patients with uc higher level of
      TAT, fibrinogen and platelets count, lower level of prekallikrein activity and
      shorter aPTT were found than in control group. No significant differences in
      obtained results of hemostatic parameters between patients with active and
      inactive uc were found. Whereas, it was disclosed lower platelets count and
      fibrinogen concentration in cases with inflammatory process only to rectum
      limited in comparison with more extended inflammatory changes. Using multiple
      regression method it was found that in studied group the TAT concentration,
      marker of thrombin in vivo generation, was determined by: aPTT, fibrinogen level,
      disease severity, inflammatory process extension in large bowel, systemic acute
      phase reaction. CONCLUSIONS: 1) In patients with uc independently of activity and
      extension of inflammatory process, the increase of in vivo throminogenesis
      expressed by higher TAT level was found. 2) Observed coagulation system
      disturbances may exert an influence on inflammatory process affecting large bowel
      and increase the risk of thrombotic complications in the course of uc.

PMID- 11236259
TI  - [Clinical course and long-term prognosis in patients with recurrent myocardial
      infarction].
AB  - Retrospective study was based on analysis of 881 patients treated in our ward in
      1992-1996. Their fate was estimated through 2-6 years after the past myocardial
      infarction (MI). There were among of them 147 (16.7%) with second and 20 (2.3%)
      with third or next MI. Then we compared in-hospital course and long-term
      prognosis in patients with recurrent MI (group I, n = 167) to patients with the
      first MI (group II, n = 714). We have also evaluated influence of the time-period
      between the both episodes of myocardial infarctions on the prognosis. The chi
      square test was applied to identify the significance of the difference between
      both groups. Using the Kaplan-Meier method, figures of survival curves were
      created. Patients in group I were about 4.9 year-older than in group II/(median
      age was 64.8 +/- 10.7 vs 59.9 +/- +/- 11.3 years p < 0.05). More popular were
      also diabetes (30.5% vs 18.5%, p < 0.001), advanced hypertension (31.7% vs 20.5%
      p < 0.01) and higher ratio of current smokers (51.5%) among risk factors in
      patients from group I. Second myocardial infarction had more serious in-hospital
      course than the first one. It could be the result of anterior location and more
      often cardiac complications like ventricular arrhythmias including VF,
      disturbances of intraventricular conductions, cardiogenic shock and pulmonary
      oedema with especially of first hours of acute myocardial infarction. Mortality
      rate in the group I was 2.2 times higher to compare with group II (24.0% vs
      10.9%, p < 0.001). Significance higher mortality was in the first year of follow
      up and among patients with recurrent myocardial infarction within 12 months after
      the first one. CONCLUSION: Previous myocardial infarction is significant risk
      factor that elevate in-hospital course and long-term mortality rate. We observed
      the higher mortality rate when the recurrent myocardial infarction occurred
      within 12 months after the first one. The longer time-period since the first
      myocardial infarction the better prognosis was observed in our analysis.

PMID- 11236260
TI  - [Clinical and biochemical picture of primary hyperparathyroidism based on 155
      observed cases].
AB  - In this study, the biochemical and clinical profile of primary
      hyperparathyroidism, diagnosed in 155 patients (106 females and 49 males) in the
      Department of Nephrology of the Silesian University School of Medicine in the
      years 1972-1998 was analyzed. The mean age of patients was 48.5 +/- 12.8 years.
      In all cases the diagnosis was confirmed by the pathomorphological examination.
      In the majority of cases PNP was diagnosed in a phase of advanced organic
      injuries. The leading clinical finding in these patients was nephrolithiasis.
      Asymptomatic hypercalcemia was diagnosed only in 9% of cases. In the years 1972
      1992 elevated serum total calcium concentration was found in 92.6% while after
      introduction of routine estimation of ionized calcium concentration in 1993,
      hypercalcemia was found in all patients. The incidence of hypercalciuria
      increased significantly in patients diagnosed in the period 1993-1998 while in
      this same period the incidence of impaired renal function declined significantly.
      The elevated serum PTH was found in 86% of patients regardless whether C-terminal
      fragments of PTH or intact PTH-1-84 were assessed. Elevated levels of ionized
      serum calcium with normal or increased plasma iPTH-1-84 level are the most
      constant symptoms of primary hyperparathyroidism.

PMID- 11236261
TI  - [Chronic eosinophilic leukemia].
AB  - In this research one case of chronic myelogenous eosinophilic leukemia (pbe)
      transformed into myeloblastic crisis in male patient aged 24, efficiently treated
      chemotherapy with following performing allogenic bone marrow transplantation was
      represented. The patients was admitted to the Department of Hematology with the
      cause of increased leucocytosis (up to 19.9 x 10(9)/l), eosinophilia (up to 15.3
      x 10(9)/l), enlarged percentage of eosinophillic granulocytes in bone marrow,
      splenomegaly, anaemia and thrombocytopenia. Cytogenetic tests did not reveal any
      chromosomal disturbances, and PCR test did not detect bcr/abl rearanzation. After
      7 monthly period of chronic phase of disease there was appeared symptoms of
      blastic acceleration myelogenous disease i.e. enlargement of splenomegaly,
      intensification of anaemia and thrombocytopenia, very fast increasing
      leucocytosis in short time together with presence of myeloblasts in blood and
      bone marrow smear tests. Blastic acceleration pbe with eosinophils dominant in
      bone marrow was confirmed by flow cytometry. Induction chemotherapy according to
      schedule HAR (Hydroxyurea--H, Arabinoside Cytosine--A, Doxorubicin--R),
      consolidation and irradiation of spleen allowed to receive complete remission.
      The patients was undergone allogenic bone marrow transplantation (allo-BMT) from
      related donor (younger brother). The follow-up with the period 18 months after
      allo-BMT has not revealed the relapse of disease.

PMID- 11236262
TI  - [Observation of D-dimer levels in serum of patients with acute leukemia].
AB  - The blood coagulation and fibrinolysis disorders are common complications
      observed in patients with acute leukemias, particularly in acute myelogenous
      leukemia. These abnormalities are mediated by thromboplastic substances released
      from the blast cells and the alteration of hemostatic properties of vascular
      endothelium. The plasma concentration of D-dimer (cross-linked fibrin degradation
      products), measured by enzyme immunoassay, using monoclonal antibodies, serves as
      a specific marker of the coagulation activation and fibrinolysis system. In our
      study, the plasma concentration of D-dimer was investigated in 142 patients with
      acute leukemia during clinical course--at the time of initial diagnosis, complete
      remission, relapse or in cases resistant to chemotherapy. It has been revealed
      that, at the time of initial diagnosis, the plasma level of D-dimer was elevated
      in most patients, irrespective of the type of acute leukemia. However, the
      initially elevated plasma concentration of D-dimer was significantly lower when
      complete remission had been achieved. Furthermore, in the majority of cases of
      relapse or resistance to chemotherapy, a further increase of plasma concentration
      of D-dimer is commonly observed.

PMID- 11236263
TI  - [Permanent heart pacing in treatment of cardioinhibitory vasovagal syncope (case
      report)].
AB  - Vasovagal syncope is a complex syndrome in which specific methods of treatment
      rarely are related to clinical success. Since it turned out that some patients
      with neurocardiogenic syncope were resistant to offered pharmacotherapy, cardiac
      pacing has been used as the alternative way of long-term therapy. Successive
      studies, which have estimated clinical efficacy of permanent cardiac pacing,
      indicate that such method of treatment may reduce symptoms revealed by vasovagal
      reflex. Nevertheless the optimal pacing mode has not been established yet. It is
      known that single chamber VVI pacing is not a good and effective method whereas
      dual chamber DDI pacing with rate hysteresis seems to be very promising in
      treatment of people suffering from malignant cardioinhibitory vasovagal syncope.
      DDD pacing with rate drop response, search and scan functions recently has been
      available to these patients. The results of the North American Vasovagal
      Pacemaker Study, as well as some casuistic observations referring to patients
      with vasovagal syndrome, show very high clinical efficacy of dual chamber pacing
      with mentioned new functions. We present a case of patient with cardioinhibitory
      vasovagal syncope who was successfully treated by permanent DDD pacing with
      search and scan hysteresis.

PMID- 11236264
TI  - ["POEMS" syndrome--activation of the cytokine network].

PMID- 11236265
TI  - [Pro-inflammatory cytokines and transforming growth factor-beta 1 in POEMS
      syndrome].

PMID- 11236266
TI  - [Cigarette smoking influences treatment efficacy of peptic ulcer disease: fact or
      fancy?].

PMID- 11236268
TI  - Clinical and endoscopic aspects in the evolution of patients with bleeding peptic
      ulcer--a cohort study.
AB  - BACKGROUND: Bleeding ulcers are a major problem in public health and represent
      approximately half of all the cases of upper gastrointestinal hemorrhage in the
      United States. This study aims to determine the prognostic value of factors such
      as clinical history, laboratory and endoscopic findings in the occurrence of new
      episodes of bleeding in patients who have upper gastrointestinal hemorrhage
      caused by gastric or duodenal peptic ulcer. METHODS: A cohort study with 94
      patients was designed to investigate prognostic factors to the occurrence of new
      episodes of bleeding. RESULTS: From the 94 patients studied, 88 did not present a
      new bleeding episode in the 7 days following hospital admission. The incidence of
      rebleeding was significantly higher in those patients with hemoglobin < 6 g/dL at
      the admission (P = 0.03, RR = 6.2). The localization of the ulcers in bulb was
      positively associated to rebleeding (P = 0.003). The rebleeding group needed a
      greater number of units transfunded (P = 0.03) and the time of hospitalization
      was longer than the time of the hemostasia group (P = 0.0349). CONCLUSIONS: The
      identification of patients with risk of death by bleeding peptic ulcer remains as
      a challenge, once few factors are capable of predicting the severity of the
      evolution. The identification of such factors will allow the choice of the better
      therapeutic conduct improving the diagnosis and decreasing the rate of rebleeding
      and the mortality.

PMID- 11236267
TI  - [Sclerotherapy versus somatostatin in the treatment of upper digestive hemorrhage
      caused by rupture of esophageal varices].
AB  - The aim of this study was to compare the efficacy of somatostatin versus
      endoscopic sclerotherapy in the management of digestive bleeding caused by
      rupture of esophageal varices. Forty patients were evaluated; 21 were randomly
      assigned to receive somatostatin (initial 250 micrograms followed by a 48-hour
      continuous infusion of 250 micrograms/h and 250 micrograms 6/6 h bolus in the
      first 24 hours) and 19 to receive endoscopic sclerotherapy with ethanolamine
      oleate 5%. The patients were evaluated after 48 hours and after 7 days of
      treatment. Both groups of patients were similar in sex, age, gravity of the
      hemorrhage and liver dysfunction. Therapeutic failure occurred in 26.3% and 35.7%
      in the group of endoscopic sclerotherapy (48 h and 7 days respectively), and in
      23.8% and 21.4% in the group of somatostatin. The need of blood transfusion (3.38
      U in the group of endoscopic sclerotherapy and 2.42 U in the group of
      somatostatin) and the mortality rate (31.6% in the group of endoscopic
      sclerotherapy and 28.6% in the group of somatostatin) were also similar (P >
      0.05). The authors conclude that somatostatin is as effective as endoscopic
      sclerotherapy and that it should be considered in the treatment of acute
      esophageal variceal bleeding.

PMID- 11236269
TI  - [Distal gastric carcinoma with duodenal invasion. Histopathologic study and
      review of the literature].
AB  - Gastric carcinoma with duodenal invasion is reported in 11% to 33.3% of surgical
      specimens. In spite of this high frequency, it is not easily recognised during
      the surgical proceeding or at gross examination. The study of risk factors like
      histological type, tumor stage and extension of duodenal invasion can be useful
      in establishing the best surgical approach in order to diminish the risk of local
      recurrence. We report 50 cases of distal gastric carcinoma in which we analysed
      the tumor extension in the different layers of the duodenal wall; duodenal
      invasion was correlated with histological type, level of infiltration in the
      gastric wall and presence of vascular invasion. Duodenal invasion was observed in
      27 cases (54%), 17/32 of intestinal type (53%), 9/10 of diffuse type (90%) e 1/8
      of non-classifiable tumours (12.5%). Diffuse type carcinoma was the most
      important risk factor for invasion (OR = 11; CI 95%: 1.20 to 254.16; P < 0.01).
      Most of the cases (21/27, 77%) were stage III or IV. The submucosal layer was the
      most frequent (22/27 cases, 81%) and also most extensively (8.21 +/- 9.75 mm)
      invaded. We conclude that the risk of duodenal invasion is higher in diffuse type
      tumours and in stage III or IV. Distal surgical resection should be wider in
      these cases and determined by frozen section biopsy specimen at the point of
      transection.

PMID- 11236270
TI  - Malignancy risk prediction for primary jejunum-ileal tumors.
AB  - This work is aimed at identifying factors associated with primary jejunum-ileal
      tumors malignancy, defining a prediction model with sensitivity, specificity and
      accuracy to distinguish malign from benign neoplasms. These tumors are rare, have
      highly unspecific presentation and, frequently, are diagnosed late. We reviewed
      the charts of 42 patients with primary jejunum-ileal tumors treated in the
      Department of General Surgery of Rio de Janeiro State University Hospital, Rio de
      Janeiro, RJ, Brazil, from 1969 to 1998. We performed bivariate analyses, based on
      chi 2 test, searching associations between tumors malignancy and demographic and
      clinical variables. Then logistic regression was employed to consider the
      independent effect of variables previously identified on malignancy risk. The
      malign tumors included 11 adenocarcinomas, 7 leiomyosarcomas, 5 carcinoids and 4
      lymphomas; the benign tumors included 10 leiomyomas, 2 hamartomas, and single
      cases of adenoma, multiple neurilemoma and choristoma. The bivariate analyses
      indicated the association between malignancy and palpable abdominal mass (P =
      0.003), period from signs and symptoms onset to diagnosis (P = 0.016), anemia (P
      = 0.020), anorexia (P = 0.003), abdominal pain (P = 0.031), weight loss (P =
      0.001), nausea and vomit (P = 0.094), and intestinal obstruction (P = 0.066); no
      association with patients demographic characteristics were found. In the final
      logistic regression model, weight loss, anemia and intestinal obstruction were
      statistically associated with the dependent variable of interest. Based only on
      three variables--weight loss, anemia and intestinal obstruction--the model
      defined was able to predict primary jejunum-ileal tumors malignancy with
      sensitivity of 85.2%, specificity of 80.0%, and accuracy of 83.3%.

PMID- 11236271
TI  - Gastric cryptosporidiosis as a clue for the diagnosis of the acquired
      immunodeficiency syndrome.
AB  - Cryptosporidium parvum has been detected with increasing frequency in the
      gastrointestinal tract, but involvement of the stomach is rarely reported.
      Whenever found in the histologic examination of the gastrointestinal mucosa, it
      should raise the suspicion of an immunocompromised host. We report a case of
      Cryptosporidium-associated erosive gastritis in a 64-year-old woman, who was
      found later to have the acquired immunodeficiency syndrome.
      Gastroduodenoendoscopy and biopsy of the gastric mucosa played an invaluable role
      in the diagnosis of cryptosporidiosis and to disclose the underlying
      immunodeficiency state.

PMID- 11236272
TI  - [Laparoscopic treatment of common bile duct lithiasis].
AB  - With the advances of videolaparoscopic surgery, this approach had become the
      treatment of choice for cholelithiasis. However, about 5% to 10% may present
      common bile duct lithiasis. Most surgeons have still difficulties to deal with
      this situation and do prefer resolve with open surgery or with further endoscopic
      approach. We present a case of a 60-year-old man, with 18 months history of right
      upper quadrant pain, weight loss and jaundice. He was referred with diagnostic of
      pancreatic cancer. Laboratory investigation showed increased bilirubin (10
      mg/dL), alkaline phosphatase and GGT. Abdominal ultrasound showed atrophic
      gallbladder with dilated intra and extrahepatic biliary tree. Computerized
      tomography scan disclosed enlarged biliary tree with 3 cm stone in the distal
      common bile duct. The patient underwent a laparoscopic cholecystectomy followed
      by choledochotomy and retrieval of the large stone. A latero-lateral
      choledochoduodenum anastomosis was then performed to decompress the biliary tree.
      The patient had an uneventful recovery being discharged at the 6th postoperative
      day. Laparoscopic management of choledocholithiasis is feasible in many patients,
      specially those with dilated biliary tree. The retrieval of stones may be
      followed by biliary drainage with T-tube. In some elderly patients with
      chronically dilated common bile duct, as in the present case, a
      choledochoduodenal anastomosis is the procedure of choice.

PMID- 11236273
TI  - [Chronic viral hepatitis C. Part 1. General considerations].
AB  - Hepatitis C virus was identified in 1989 as the main causative agent of non-A,
      non-B and was followed by the recognition of a high prevalence of hepatitis C
      virus infection after transfusion of infected blood or blood products and in
      association with intravenous drug abuse. The availability of sensitive and
      reliable techniques to screen blood for hepatitis C virus has reduced the
      incidence of post-transfusion hepatitis. True healthy carriers of hepatitis C
      virus did not exist. Approximately 95% of hepatitis C virus infected individuals
      can be identified by third generation anti-hepatitis C virus testing.
      Retrospective studies of iatrogenic hepatitis C virus infection are the main
      source of the natural history of the disease. The distribution of different
      hepatitis C virus genotypes varies according to the geographic region. In South
      America, Europe, The United States and Japan hepatitis C virus genotypes 1, 2 and
      3 account for the majority of the infections, being (sub)type 1b the most
      prevalent. Epidemiological parameters (age, risk factors and duration of
      infection) may be associated with hepatitis C virus genotypes (intravenous drug
      abuse with types 1-a and 3-a and 1-b with post-transfusion hepatitic C). Subtype
      1-b, lead to a more severe course of viral infection, with ultrastructural
      alterations of the mitochondria, and greater impairment of the process of
      oxidative phosphorylation. No increased production of free radicals may influence
      the evolution of the liver disease by an enhancement of the cytopathic effect of
      hepatitis C virus. The clinical significance of intrahepatic hepatitis C virus
      level in patients with chronic hepatitis C virus infection is not determined by
      host factors (age of patient, mode or duration of infection) or by virus factors
      (hepatitis C virus genotypes) and, repeatedly negative RT-PCR for hepatitis C
      virus RNA in serum does not indicate absence of hepatitis C virus from the liver.
      The association between autoimmunity and hepatitis C virus is questioned. Markers
      of its does occur with high frequency in these patients. Modulation of immune
      responses to hepatitis C virus envelope E2 protein following injection of plasmid
      DNA, has been used for induction of specific response to hepatitis C virus. The
      spectrum of such responses could likely be broadened by combining plasmids,
      delivery routes, and other forms of encoded immunogens (peptide vaccines). These
      may be important to the development of a vaccine against the high mutable
      hepatitis C virus. The pathogenic role of novel DNA virus (TTV) is under
      spotlight. As with hepatitis G, however, the association of TTV with disease is
      far from clear.

PMID- 11236274
TI  - Indices for nutritional condition and thresholds for winter survival in sika deer
      in Hokkaido, Japan.
AB  - We derived fat indices for sika deer (Cervus nippon yesoensis) in eastern
      Hokkaido, Japan, and estimated the probability of over-winter survival with a
      logistic regression model using fat indices. Kidney fat mass (KFM) appears to be
      an adequate index of wide range of physical conditions before the onset of severe
      nutritional stress. When KFM values fell below 20 g, femur (FMF) and mandible
      cavity fat (MCF) indices declined sharply. FMF and MCF were useful indices for
      detecting malnourished deer. A logistic regression model describes survival
      thresholds in two bone fat indices for calves (45%) and three fat indices for
      adult females (FMF = 25%, MCF = 30%, KFM = 20 g). These models are useful for
      estimating the probability of winter survival in Hokkaido sika deer.

PMID- 11236275
TI  - An analysis of the growth based on the size and age distributions of the
      hawksbill sea turtle inhabiting Cuban waters.
AB  - The first costal scute (C 1) collected from 2, 749 hawksbill turtle (Eretmochelys
      imbricata) captured in Cuban waters in 1993 and 1994 were analyzed to determine
      their body size and age distributions. The C 1 width (C 1 W) was converted to the
      straight carapace length (SCL) using a formula, SCL = 4.3527 (C 1 W)0.8484, to
      examine its body size distribution. The SCL ranged from 51.3 to 96.1 cm with 68.8
      cm of mean and 68.6 cm of median. Ages of captured turtles estimated from the C 1
      surface patterns were ranged from 3.3 to 61.5 years old with 15.8 years of mean
      and 14.5 years of median. A growth function of van Bertalanffy, M(t) = A(1-Be
      kt), was applied to determine the relationship between the age and body size
      (SCL). A formula, SCL = 80.4(1 -0.663e-0.118(Age)), was derived and indicated a
      slowdown in the growth after about 14 years old. The maturation age and the rate
      of sexually matured Cuban hawksbill turtles were also discussed based on these
      results.

PMID- 11236276
TI  - Parasitic forms of a myxosporean in the kidney of the arctic lamprey, Lampetra
      japonica: an ultrastructural study.
AB  - We found frequent and unique parasitism by an unidentified myxosporean in the
      kidney of the arctic lamprey, Lampetra japonica, living in Japan. Trophozoites
      (pseudoplasmodia with or without sporoblasts) existed predominantly in the lumina
      of proximal urinary tubules, but were rarely found in any other regions of the
      kidney. Since no mature spores were produced in the trophozoites, exact
      identification of the species was impossible. Two parasitic forms were recognized
      in proximal urinary tubules: one adhering to the epithelial cells of renal
      tubules, and the other free-floating in the lumina of tubules. Ultrastructurally,
      the attaching trophozoites developed microvilli-like projections towards the
      apical surface of epithelial cells and vigorously interdigitated with microvilli
      of the brush border. In contrast, the whole surface of the floating trophozoite
      was smooth without any cell projections. The developed projections in the former
      type of trophozoite may contribute to their firm attachment to the epithelial
      cells and/or to absorption of nutrients via the epithelial cells. Against the
      myxosporean infection, the lamprey as the host exhibited a local immune reaction
      by disposition of numerous lymphocytes and macrophages into the epithelium of
      urinary tubules.

PMID- 11236277
TI  - Cardiovascular disease: a historic perspective.
AB  - Cardiovascular disease (CVD) is the leading cause of death and disability in the
      United States and in most industrialized nations. Major breakthroughs to modern
      day cardiovascular/lipid research have been attributed to the findings of the
      Framingham Heart Study and Gofman and colleagues who made associations between
      lipoprotein levels (LDL, VLDL and HDL) and CVD. Unfortunately, half of all CVD
      patients have none of the established coronary risk factors (hypertension,
      hypercholesterolemia, cigarette smoking, diabetes mellitus, obesity) and new
      strategies for identifying patients need be considered. Although there remains
      little disagreement regarding the necessity to lower elevated plasma cholesterol
      levels, there remains much controversy regarding appropriate dietary means of
      accomplish this goal. The National Cholesterol Education Program (1993) proposed
      a dietary reduction (Step I and Step II diets) to the percent saturated fat and
      cholesterol consumed by at-risk patients. Many currently question about the
      effectiveness of these diets and an alternative diet, replacing saturated fats by
      monounsaturated fats (olive oil), has attracted recent attention. While diet
      modification is considered the foundation of primary treatment, other
      interventions are frequently required. Although early drug trials demonstrated
      that agents such as nicotinic acid, clofibrate, gemfibrozil, bile acid-binding
      resins generally slowed progression of atherosclerotic lesions, lowered plasma
      cholesterol levels and decreased mortality from CVD, the greatest advance to
      current drug therapy involved the discovery of the "statins" (HMG-CoA reductase
      inhibitors). In the current work, mechanisms for vascular dysfunction resulting
      in myocardial ischemia were explored and potential nutritional (dietary) and
      pharmacologic interventions were reviewed.

PMID- 11236279
TI  - Ready? What to expect from rehabilitation PPS.
AB  - Rehabilitation hospitals and units are the next providers to take on the Health
      Care Financing Administration's prospective payment system (PPS). As the
      rehabilitation PPS takes effect April 1, rehab case managers and other
      professionals face the daunting task of learning to use the Minimum Dataset Post
      Acute Coding and the new functionally related group billing system. It promises
      to offer initial financial confusion and coding challenges as rehab professionals
      learn the new techniques and how to use them effectively. Hospitals and units
      will be searching for new strategies to be sure they survive economically and
      productively in the coming years.

PMID- 11236278
TI  - Reduce costs, improve outcomes with community case management.
AB  - Community case management is coming of age in a time of increasing government
      cuts to funding for Medicare patients and home health agencies. A hospital-based
      community case management program can save real dollars by offering a continuum
      of care for elderly and chronically ill patients who might otherwise need
      emergency room visits, readmissions, and visits to physicians' offices. Obstetric
      and psychiatric patients can benefit, too. And it doesn't need to be a budget
      killer. Minimal expenses and volunteer services can keep a community case
      management program budget-friendly within almost any health care center.

PMID- 11236280
TI  - Home health PPS makes discharge planning harder.
AB  - HCFA's new prospective payment system for home health represents a challenge to
      hospital case managers as well as the home health industry. With funding reduced
      and documentation increased, many home health agencies find themselves scrambling
      to serve patients and break even financially. Case managers have had to worry
      about whether agencies will be able to accept the patients that hospitals send
      their way. Agencies are anxious about the demands on their time and productivity.
      It's been a tough adjustment with a long learning curve, and things are still in
      flux.

PMID- 11236281
TI  - Improving client education with the patient pathway.

PMID- 11236282
TI  - Regs up EMTALA ante: help 'remote site' staff comply.

PMID- 11236283
TI  - Management of uterine fibroids.

PMID- 11236284
TI  - South African medical ethics: Biko, Basson, Bezwoda ... what's next?

PMID- 11236285
TI  - Abuse of the surgical assistant's fee.

PMID- 11236286
TI  - Abuse of the surgical assistant's fee.

PMID- 11236287
TI  - Abuse of the surgical assistant's fee.

PMID- 11236288
TI  - Greed versus health.

PMID- 11236289
TI  - Pot--the pitfalls of pragmatism.

PMID- 11236290
TI  - Ultrasound knowledge appalling.

PMID- 11236291
TI  - Unscrupulous get fat on yuppie flu.

PMID- 11236292
TI  - E.M.--a compelling new specialty.

PMID- 11236293
TI  - Celecoxib--a rational alternative to NSAIDs.

PMID- 11236294
TI  - Curing cancer in children--early recognition and appropriate treatment are the
      key.

PMID- 11236295
TI  - The patient-physician relationship--a return to paternalism?

PMID- 11236296
TI  - Acceptability of prenatal, voluntary HIV counselling and testing and
      interventions to reduce mother-to-child transmission of HIV infection in rural
      South Africa.

PMID- 11236297
TI  - The effectiveness of weekly iron and vitamin supplementation of Malawian
      preschool children.

PMID- 11236298
TI  - Evaluation of the biological safety of condoms using an in vitro cell culture
      method.

PMID- 11236299
TI  - Therapeutic equivalence study of two formulations (innovator v. generic) of
      beclomethasone dipropionate in adult asthmatic patients.
AB  - OBJECTIVE: To study the therapeutic equivalence of two formulations (innovator v.
      generic) of beclomethasone dipropionate (BDP) 400 micrograms twice daily
      administered per metered dose inhaler (MDI), in adults with moderate to severe
      asthma. METHODS: A double-blind randomised parallel-group trial was performed
      with a 2-week run-in and an 8-week treatment period. Thirty-six symptomatic adult
      asthmatics on a mean daily dose of 750 micrograms inhaled corticosteroids during
      run-in, a mean forced expiratory volume in 1 second (FEV1) of 70% predicted
      normal and a mean histamine concentration provoking a 20% reduction in FEV1
      (histamine PC20) of 0.11 mg/l were randomised to one of the two treatment groups.
      Primary variables were morning peak expiratory flow (mPEF), FEV1 and histamine
      PC20. Secondary variables were beta 2-agonist use, symptom score and nocturnal
      awakening. The Schuirmann two one-sided tests procedure was used for the
      statistical analysis. Ninety-five per cent confidence intervals (CIs) were
      calculated for the differences in means. RESULTS: The mean differences end of
      treatment to baseline for the two formulations (Becotide and Beclate)
      respectively were: mPEF 5.6 l/min (CI - 16.4-27.6) and -22.3 l/min (CI -35.6(-)
      9); FEV1 -2.9% (CI -11-5.2) and 0.2% (CI -4.8-5.2); Histamine PC20 -0.04 mg/ml
      (CI -0.15-0.06) and 0.02 mg/ml (CI -0.37-0.4). Changes in clinical variables were
      not conclusive. The mean differences with CIs for primary variables were
      contained within the limits set for equivalence. The sample size was sufficient
      to differentiate the groups for mPEF, but this was not of clinical significance.
      CONCLUSION: After 8 weeks of treatment the two formulations of BDP, delivered by
      MDI through a large-volume spacer, were therapeutically equivalent in moderate-to
      severe asthmatic adults.

PMID- 11236300
TI  - Occupational exposure of interns to blood in an area of high HIV seroprevalence.
AB  - OBJECTIVE: To determine the epidemiology of work-related exposure to blood among
      interns. DESIGN: Interns were invited to complete anonymously a questionnaire
      concerning their past percutaneous and mucocutaneous exposures to blood. SETTING:
      Chris Hani Baragwanath Hospital, Soweto, and Johannesburg Hospital, Gauteng,
      where HIV infection is common among patients. RESULTS: Ninety-eight interns (96%)
      were surveyed. Sixty-nine per cent of interns reported one or more percutaneous
      exposures to blood during the intern year, and 33% of interns recalled accidental
      percutaneous exposure to HIV-infected blood. Forty-five per cent recalled a
      mucocutaneous exposure to HIV-positive blood. Only 28 (64%) of 44 percutaneous
      injuries from HIV-infected patients were reported. During their student clinical
      training, 56% of interns had suffered a penetrating injury, and 18% recollected
      needlestick injuries involving HIV-infected patients. The most common mechanisms
      of injury included unexpected patient movement (23%), needle recapping (17%), and
      withdrawal of the needle (17%). Half of the injuries occurred during the first 4
      months of internship. Only 22% of intern percutaneous exposures could have been
      avoided by following universal precautions. CONCLUSIONS: Intern and medical
      student exposure to blood is extremely common, but is markedly underreported.
      Strict compliance with universal precautions will not prevent the majority of
      exposures. Priorities should be the introduction of safer techniques and
      equipment, skills training and methods of reporting blood exposures.

PMID- 11236301
TI  - Renal function, sodium and water homeostasis in patients with idiopathic
      extrahepatic portal vein thrombosis compared with normal healthy controls.
AB  - OBJECTIVES: To determine whether portal hypertension in the absence of liver
      disease contributes to changes in renal function and renal sodium and water
      handling. METHODS: Nine patients with extrahepatic portal vein thrombosis (PVT)
      with normal liver function and histology were compared with 9 matched healthy
      control subjects. All underwent standard measurements of glomerular filtration
      rate and effective renal blood flow using inulin and paraaminohippuric acid (PAH)
      clearances, respectively. Sodium excretion and renin and aldosterone levels were
      studied before, during and after an intravenous saline infusion. RESULTS: At
      baseline there were no differences in inulin clearance, PAH clearance, fractional
      excretion of sodium and free water excretion. During and after the saline
      infusion both groups showed a significant increase in sodium excretion with a
      reduction in water excretion, while the PAH and inulin clearances remained
      unchanged. Although aldosterone and renin levels both fell after the infusion,
      aldosterone levels were significantly lower in the PVT group. There were no other
      significant differences between the PVT and control groups. CONCLUSION: Renal
      function and sodium and water handling were comparable in healthy controls and
      patients with PVT. It is unlikely that portal hypertension alone plays a
      significant role in the impaired ability to excrete sodium and water in patients
      with liver cirrhosis.

PMID- 11236302
TI  - Day clinics and hospitals--a cost comparison.
AB  - OBJECTIVE: To determine the types of surgical procedures currently undertaken in
      day clinics and to compare the number of procedures, the average in-facility
      cost, and the pre- and post-discharge costs for each procedure or group of
      procedures. DESIGN: A retrospective descriptive study of medical aid claims data.
      SETTING: Department of Family Medicine, University of the Witwatersrand,
      Johannesburg. SUBJECT: Three private sector medical aid schemes with in excess of
      170,000 principal members (380,000 lives). OUTCOME MEASURES: For each surgical
      procedure the following were compared: (i) the total number of procedures done;
      (ii) the average total in-facility cost; and (iii) the cost of professional fees
      and medicines for 7 days before admission, during admission, and for 14 days
      after discharge. RESULTS: During 1997, 89,216 patients underwent surgery. Day
      clinics and hospitals accounted for 5,490 and 83,726 admissions respectively.
      Fifty-one different types of procedures were identified that met the inclusion
      criteria. On average the in-facility costs for 45 (88%) of the 51 compared
      procedures were lower in day clinics compared with hospitals. Average costs can
      be as much as 90% lower in day clinics. Some procedures, particularly certain
      dental operations, cost more in day clinics. The professional fees of attending
      doctors and the cost of medicines are generally higher when the procedure is
      undertaken in a hospital. CONCLUSION: In South Africa, as is the case in the USA,
      day clinics have the potential to reduce the cost of surgical procedures.

PMID- 11236303
TI  - Risk factors for teenage pregnancy among sexually active black adolescents in
      Cape Town. A case control study.
AB  - MOTIVATION: Teenage pregnancy is an important health and social problem in South
      Africa. So far research on adolescent sexual activity has been almost exclusively
      descriptive; as a result there is considerable knowledge about practices of
      adolescents in general and outcomes of their pregnancies, but very limited
      understanding of factors that place particular adolescents at increased risk of
      teenage pregnancy. Without this understanding, our ability to intervene
      effectively to reduce teenage pregnancy rates is limited. OBJECTIVE: To undertake
      an exploratory study to investigate risk factors for teenage pregnancy among
      sexually active adolescents in an urban and peri-urban context. METHODS: The
      study used a matched case-control design, with 191 cases and 353 age-matched
      controls from the same school or neighbourhood. Subjects were under 19 years of
      age and were recruited from township areas of Cape Town. A structured
      questionnaire was used to obtain information on socio-economic factors,
      contraceptive knowledge and use, and sexual behaviour. Conditional logistical
      regression was used to analyse the relationship between teenage pregnancy and the
      factors investigated. RESULTS: Teenage pregnancy was found to be most strongly
      associated with having frequent sex (risk ratio (RR) 30.81) without reliable
      contraceptive protection (RR 24.35), forced sexual initiation (RR 14.42), not
      owning a television set (RR 10.33), larger household size (RR 2.44), not living
      in a brick house (RR 5.09), not living with the biological father (RR 3.26),
      talking openly about sex with a boyfriend (RR 4.72), and perceiving most friends
      to be pregnant (RR 4.38). CONCLUSIONS: The findings suggest associations between
      the promotion of sexual health among adolescents and broader social development
      and promotion of gender equality. Although further research is needed, it is
      likely that important foci for short-term strategies should include developing
      assertiveness, enhancing decision-making competence, and promoting contraception
      and condoms as part of comprehensive sexual and reproductive health educational
      interventions.

PMID- 11236304
TI  - The cholera epidemic--a (belated) media circus.

PMID- 11236305
TI  - HIV--the threat to South Africa's blood transfusion services.

PMID- 11236306
TI  - Diagnosis and management of dental caries.

PMID- 11236307
TI  - Adjuvant therapy for rectal cancer: results and controversies.
AB  - During the past decade, advances have been made in the adjuvant treatment of
      resectable rectal cancer. Postoperative combined-modality therapy significantly
      improves local control and survival. Recent Inter-group postoperative trials have
      focused on the identification of optimal chemotherapeutic agents and their method
      of administration. Preoperative therapy has the potential advantages of producing
      less acute toxicity and increasing the likelihood of sphincter preservation. New
      chemotherapeutic agents and radiation techniques are active areas of
      investigation.

PMID- 11236308
TI  - Nutritional implications of dental and swallowing issues in head and neck cancer.
AB  - Tumors of the head and neck account for 4% of cancers in the United States. Both
      the disease process itself and side effects of cancer treatment, such as
      xerostomia, dysphagia, and malnutrition, compromise oral health, swallowing
      ability, and nutritional status. Optimal treatment of dental, swallowing, and
      nutritional problems of head and neck cancer patients requires practical
      strategies that address these problems. These strategies should include
      appropriate referrals to the dentist, speech/language pathologist, and registered
      dietitian to enhance patient comfort, prevent secondary malnutrition and dental
      disease, and improve treatment outcomes. Since dental, swallowing, and
      nutritional issues are interrelated, appropriate therapeutic strategies hinge on
      timely, integrated input from each discipline. A better understanding of the
      dental and swallowing therapies used in patients with head and neck cancer by
      health professionals will help promote the comprehensive care of these patients.

PMID- 11236309
TI  - Clinical trails referral resource. Clinical trials of adenovirus-p53 gene
      therapy.

PMID- 11236310
TI  - Clinical uses of radiosurgery.
AB  - Radiosurgery uses stereotactic targeting methods to precisely deliver highly
      focused, large doses of radiation to small intracranial tumors and arteriovenous
      malformations (AVMs). This article reviews the most common clinical applications
      of radiosurgery and the clinical results reported from a number of series using
      either a cobalt-60 gamma knife or linear accelerator as radiation sources.
      Radiosurgery is used to treat malignant tumors, such as selected cases of brain
      metastases and malignant gliomas (for which stereotactic radiosurgical boosts are
      utilized in conjunction with fractionated radiation therapy), as well as benign
      tumors, such as meningiomas, acoustic neuromas, and pituitary adenomas. Treatment
      of small AVMs is also highly effective. Although radiosurgery has the potential
      to produce complications, the majority of patients experience clinical
      improvement with less morbidity than occurs with surgical resection.

PMID- 11236311
TI  - Controversies in the management of stage I seminoma.
AB  - Current controversies in the treatment of stage I seminoma center on the relative
      roles of surveillance, adjuvant radiotherapy (RT), and adjuvant single-agent
      chemotherapy. Surveillance has been studied in over 800 patients, 17.1% of whom
      have relapsed. There is no evidence that surveillance compromises survival in
      properly selected, compliant patients. The economic benefit of treating only
      those patients who relapse is offset by the cost of screening diagnostic studies
      and salvage therapy, and by issues of patient anxiety and compliance. Other
      methods of reducing the toxicity of RT include reductions in RT dose and volume.
      A randomized trial has shown that omission of the pelvic field produces relapse
      free survival equivalent to that achieved with pelvic plus para-aortic RT. A
      similar study is currently evaluating a reduction in RT dose from 30 to 20 Gy.
      Early results from nonrandomized studies of one or two cycles of single-agent
      chemotherapy demonstrate efficacy comparable to RT in the adjuvant treatment of
      stage I seminoma. A randomized trial is underway to determine the equivalence of
      adjuvant carboplatin (Paraplatin) and RT. Long-term follow-up from these studies
      will provide information not only on the relative efficacy of these alternative
      strategies but also on the late effects of therapy, including infertility and
      second malignancy.

PMID- 11236312
TI  - Predisposition testing for inherited breast cancer.
AB  - Predisposition testing (i.e., genetic testing that provides information about a
      person's susceptibility to disease) is now available for several inherited forms
      of cancer. Individuals who are found to have an altered gene (e.g., a germ-line
      mutation in a cancer susceptibility gene) have a higher risk of developing cancer
      than those who do not carry an altered gene. Therefore, predisposition testing
      can be a powerful clinical tool for assessing a person's risk for developing
      cancer. All health care providers, particularly cancer care providers, should be
      knowledgeable about cancer predisposition testing options. This article provides
      an overview of predisposition testing for inherited breast cancer, including
      general facts about testing, potential risks and benefits, specific genetic
      counseling issues, and molecular details of known breast cancer susceptibility
      genes.

PMID- 11236313
TI  - The anatomy of "virtual" spaces: the human body as a matrioska?

PMID- 11236314
TI  - Complications of Chiari and Salter osteotomies: a cadaver study.
AB  - Previous investigations of the Chiari and Salter osteotomies showed that
      intraoperative vessel and nerve injuries are described repeatedly in the case of
      both pelvic osteotomies. The aim of our investigations was the exposure of each
      operation step in anatomic specimens to show the anatomic landmarks and potential
      risks. We performed nine Chiari osteotomies and five Salter osteotomies on
      formalin-fixed cadavers. The operation steps were made consecutively to assess
      the risks to the vessels and nerves as well as the determination of anatomically
      important reference points. In both procedures an injury of the lateral femoral
      cutaneous nerve at the anterior access route is feasible. By ensuring that the
      skin including the lateral femoral cutaneous nerve is pulled medially, injury can
      be avoided. Additionally, too long retraction of the tensor fasciae latae muscle
      injures its nutrient vessels. An inadequate subperiosteal approach during the
      pull on the Hohmann's retractor leads to crushing and irritation of the sciatic
      nerve. Moreover, there is a risk that the superior gluteal nerve as well as the
      superior gluteal artery may be injured. An inadequate subperiosteal application
      of the medial Hohmann's retractor can endanger the obturator nerve. In the Chiari
      osteotomy there is a risk of injury to the articular branch of the superior
      gluteal nerve, which supplies parts of the ventral hip joint capsule. By
      inserting the K-wire too far medially the internal oblique muscle is endangered.
      Too prolonged retraction of the iliopsoas muscle in a Salter osteotomy can lead
      to compression of the femoral nerve. The form of the osteotomy has an influence
      on the stability of the hip joint in the course of exposure of the hip joint. On
      account of the narrow spatial connection between the anatomic pathways and the
      osteotomy area, strict subperiosteal dissection and careful use of the retractor
      are essential to avoid nerve and vessel injuries.

PMID- 11236315
TI  - Transplantation of the proximal fibula based on the anterior tibial artery.
      Anatomical study and clinical application.
AB  - The purpose of this study was to investigate the feasibility of microvascular
      transplantation, based on the anterior tibial artery, of the epiphysis and the
      proximal half of the diaphysis of the fibula. India ink injections into the
      anterior tibial artery were performed in 13 unembalmed adult cadavers, following
      which transverse frozen sections were taken. Dye was observed in the fibula, both
      within the intramedullary cavity and at the level of the periosteum, in all
      specimens. The average distal limit reached by the dye, measured from the tip of
      the epiphysis, was 10.4 cm in the intramedullary cavity and 11.8 cm in the
      periosteum. Based on these anatomical findings one case of humeral reconstruction
      has been performed with a fibular transplant, including both the epiphysis and a
      segment of diaphysis, vascularized solely by the anterior tibial artery.

PMID- 11236316
TI  - Visualisation of the portal flows by porto-scanner.
AB  - This study presents a retrospective analysis of 15 portal vein CT scans,
      conducted for the evaluation of hepatic metastasis in patients suffering from
      colorectal cancer, with the aim of verifying in vivo the presence of laminar flow
      as reported by Pironcof. After selective catheterization of the superior
      mesenteric artery, CT scans were performed during opacification of the portal
      vein. Different flows were identified by the incomplete opacification they
      induced in the portal vein. Splenic flows could always be identified, however
      right colic and superior mesenteric flows were only seen in 3 cases (20%) and
      gastrocolic flow in 2 (13.6%). Even though incremental (i.e. slower than helical)
      the CT acquisitions allowed the flows to be viewed by modifying the visualisation
      window. In vivo evidence of laminar flow is provided which supports Pironcof's
      experimental observations.

PMID- 11236317
TI  - A new approach to the classification of maxillary sinus hypoplasia with relevant
      clinical implications.
AB  - The purpose of this study was to discover the prevalence of maxillary sinus
      hypoplasia (MSH) and associated malformations. A total of 490 consecutive axial
      and coronal computerized tomographic (CT) scans of the paranasal sinuses were
      obtained from patients with chronic sinusitis. CT scans were assessed for the
      presence of MSH and associated anatomic variations. A new classification of MSH
      was made, and the diagnostic criteria listed. The frequency of anatomic
      variations coexisting with MSH was also estimated. MSH was encountered in 21
      (4.2%) of the 490 patients. Unilateral types I, II and III MSH were seen in 7
      (1.4%), 6 (1.2%) and 8 (1.6%) respectively. MSH was bilateral only in 3 (0.6%)
      patients, one of which was a bilateral type II. In the remaining two bilateral
      MSH cases, there was a type II MSH on one side and type III MSH on the other in
      each patient. Middle conchal pneumatization was the most common coexisting
      anatomic anomaly in MSH, followed by agger nasi cell, secondary middle concha,
      paradoxical middle concha and superior conchal pneumatization. A patient with MSH
      should be carefully evaluated prior to any sinus surgery in order to avoid
      surgical complications. With precise CT assessments, an MSH can be diagnosed and
      distinguished from other maxillary sinus anomalies. With the additional criterion
      of orbital enlargement, and the help of reproducible measurement techniques
      explained in this study, an objective diagnosis and classification can be made in
      further investigations of MSH.

PMID- 11236318
TI  - The growth of the upper and lower extremities of Turkish fetuses during the fetal
      period.
AB  - Prenatal analysis of the fetal structures gives us information about fetal growth
      and gestational age. The aim of this study was to investigate the morphologic
      structure of the upper and lower extremities of Turkish fetuses during the fetal
      period, to measure the morphometric values, and to determine the relationship
      between CRL (crown-rump length) and growth of the foot. In this study, 106 human
      fetuses (56 males, 50 females) without external anomalies and aged between 10-40
      post-menstrual weeks (PMW) were studied. In the upper extremity, the width of
      shoulder and the length of the arms, forearms and hands were measured. In the
      lower extremity, the width of the iliac crest, knee condyles, feet, and heels and
      the length of the thighs, legs and feet were measured. A significant correlation
      was found between all parameters taken within the fetal period and PMW (p <
      0.001). Statistically significant correlations found between foot-growth
      measurements and fetal parameters indicate that foot length may be a good
      predictor of age. The measurements of the upper and lower extremities during
      fetal period are a reliable parameter for use in the assessment of gestational
      age. These measurements are particularly useful when other parameters do not
      accurately predict gestational age in some cases such as hydrocephalus,
      anencephaly, short-limb dysplasia. Our opinion is that the measurements can be
      useful to assess gestational age in several fields such as anatomy, pathologic
      anatomy (fetopathology), forensic medicine, medical imaging, obstetrics and
      pediatrics.

PMID- 11236319
TI  - Musculo-tendinous junction of the flexor carpi ulnaris muscle. An anatomical
      study.
AB  - The aim of the study was to evaluate the occurrence of the anatomical variations
      of the musculotendinous junction of the flexor carpi ulnaris (FCU) muscle and the
      variations of its insertion onto the pisiform. One hundred cadaver specimens
      preserved according to Thiel's method were assessed. Following careful
      dissection, the distance between the musculotendinous junction and the pisiform
      and the width of the muscle belly were determined. Three typical anatomical
      variations were found: 1) a large muscle belly running distally almost to the
      insertion onto the pisiform; 2) the muscle belly ending more proximally, with
      some large fibres running parallel to the tendon and almost reaching the
      pisiform; 3) the musculotendinous junction ending more proximally, with only
      single fibres continuing distally. The length of the tendon was greater than 10
      mm. A number of variations of the distal region of FCU were observed. The
      presence of muscle fibres almost reaching the insertion point onto the pisiform
      have to be considered when interpreting MRI or ultrasound findings of this
      region.

PMID- 11236320
TI  - The fetal gallbladder: morphology and morphometry by microdissection.
AB  - Most studies of the fetal gallbladder have been performed using ultrasonography.
      The identification of the fetal gallbladder and the presence of gallstones have
      been determined this way. The purpose of this study was to investigate the
      morphology and morphometry of the actual fetal gallbladder by microdissection and
      to examine its internal features and content. Eighty-nine formalin-embalmed
      fetuses of CR age 35 mm to 342 mm, i.e. 10 weeks to 36 weeks gestational age
      (GA), were studied by hepatic evisceration. The fetal gallbladder was examined in
      situ in its bed, in relation to the umbilical vein, the anterior hepatic margin
      and its protrusion below the inferior hepatic surface of the liver. After
      excision, the form, length and diameters of the gallbladder were determined and
      its internal surface, lumen and content also examined. The mean length of the
      fetal gallbladder for the gestational ages studied ranged from 2.21 mm (10 weeks
      GA) to 281.6 mm (32 weeks GA); the mean fundal diameter ranged from 0.4 mm (one
      specimen only) to 9.42.4 mm for the same period, while the infundibular width
      ranged from 0.41 mm (one specimen only) to 9.01.6 mm, and the antero-posterior
      diameter at the fundus ranged from 0.90.3 mm to 9.03.3 mm for the same period.
      The parameters of the gallbladder for the period examined showed a curvilinear
      increase in size and were consistent with the ultrasonographic studies. The
      distance of the fetal gallbladder from the umbilical vein was variable and, as
      the gallbladder lengthened, the fundus encroached the anterior hepatic margin
      towards 34 weeks. A descent of the gallbladder from an "intra-hepatic" position
      early in fetal life to a sub-hepatic position later was clearly evident. The
      gallbladder wall was thick in early fetal life (10-13 weeks GA) and contained
      crumbly debris. Bile staining occurred at 14 weeks gestational age and the mucosa
      took on the normal appearance with the bile having an adult colour and
      consistency at 20 weeks GA.

PMID- 11236321
TI  - Experimental study of the subtalar joint axis: preliminary investigation.
AB  - An experimental study of the subtalar joint has been conducted with the aim of
      establishing its axis of movement as well as analysing the associated movement.
      For description of the axis, CT data for five positions of a single foot were
      reconstructed using a 3D programme, the 3D data was processed by Patran software.
      Measures of angular displacements were made from three amputated feet placed in a
      specially constructed foot frame. Four instantaneous axes of movement could be
      defined. Calculation of displacements showed an important rolling of the
      calcaneus (45 degrees). Tacking was evident in inversion, with an opposite
      displacement between the front and rear part of the calcaneus, whereas during
      eversion tacking affected only the rear part of the bone: these results were
      confirmed by 3D reconstructions. Henke's axis was described as that for the
      talonavicular joint, but acceptable for the subtalar joint. Several authors
      investigating the coordinates of this axis have reported large differences and
      described screw-like movements, the latter being incompatible with a fixed axis:
      instantaneous axes, however are compatible with a screw-like movement. The
      subtalar joint appears to work as a pivot joint during inversion and as a plane
      joint during eversion. Although Henke's axis has pedagogical value the subtalar
      joint has a series of instantaneous axes.

PMID- 11236322
TI  - Descriptive anatomy of the cricoarytenoid articulation: application to articular
      dynamics in carcinology.
AB  - The descriptive anatomy of the cricoarytenoid articulation provides an essential
      foundation for understanding disorders of mobility of the larynx, especially in
      carcinology. Thirteen formaline-preserved anatomic specimens of the adult larynx
      were studied and 4 pathologic larynges with loss of mobility due to a malignant
      tumor. The cricoid and arytenoid articular surfaces showed major intra- and inter
      individual variations, causing dynamic asymmetry at the glottic level. They were
      joined by a connective-elastic articular capsule bounding a cavity, characterized
      by a pseudo-meniscal synovial ridge and deep peripheral blind recesses,
      indicative of great articular mobility. The cricoarytenoid ligament shares in
      stabilizing the articulation. The posterior cricoarytenoid m. (abductor) and the
      lateral cricoarytenoid m. (adductor) have a motor innervation derived from the
      inferior laryngeal nerve, which forms an endolaryngeal arch with a ventral
      concavity, in contact with the lateral articular recess. The cricoarytenoid
      articulation thus appears as a diarthrosis possessing three degrees of liberty
      during movements of glottic abduction and adduction: an antero-posterior rocking
      movement, an antero-medial shift of the arytenoid on the cricoid, and a less
      marked axial rotation. Histological study of the cricoarytenoid articulation
      where mobility was reduced by carcinomatous infiltration showed that each
      articular component may be affected (muscles, cartilage, capsule, nerve), and
      that several components may be involved simultaneously to a minimal degree. The
      therapeutic implications are important, particularly in conservative laryngeal
      surgery.

PMID- 11236323
TI  - Microvascularisation of lips in ageing edentulous subjects.
AB  - Macroscopic changes of the lips in the edentulous elderly subject are accompanied
      by variations in their microvascularisation. This study was undertaken on
      histological or clarified sections from totally edentulous subjects whose
      vascular system was injected with Indian ink agar. A reduction in density and
      size of the superficial (papillary or mucosal) and deep (reticular or submucosal)
      networks is observed with age. These changes are to be seen in relation to
      imaging and to the reduction in occlusal potential of the lips.

PMID- 11236324
TI  - Tubular duplication of the esophagus. Contribution of magnetic resonance imaging
      in anatomical analysis before surgery.
AB  - The authors report a tubular duplication of the thoracic esophagus in a 17-year
      old male. This anomaly, rare in the adult, can be explained either by a failure
      of esotracheal compartmentalisation, or a notochordodysraphy or more probably by
      an error during vacuolisation of the esophagus. The anatomical characteristics of
      the duplication were clearly seen on MRI. This investigation showed the
      intramural duplication, with only a thin barrier without muscle, between the
      esophageal lumen and the duplication channel: two communications were present
      between the esophageal lumen and the duplication. The esophagus was accessed by
      right thoracotomy. The close contact between the duplication and the esophagus
      did not allow them to be separated. A subtotal esophagectomy was necessary, with
      digestive continuity being restored by coloplasty after a left cervicotomy and a
      laparotomy. The anatomy seen on the MRI should have predicted that an
      esophagectomy was necessary and that a thoracotomy could have been avoided by
      performing the procedure with a closed thorax.

PMID- 11236325
TI  - Anomalies of lateralization in man: a case of total situs inversus.
AB  - Total or complete visceral situs inversus is the complete inversion of position
      of the thoracic and abdominal viscera. The aim of this study is to report a case
      of complete situs inversus and to review our knowledge of the anomalies of
      lateralization. A case of complete sinus inversus was discovered incidentally
      during anatomic dissection in a female subject aged 87 years. The thoracic and
      abdominal organs had a position symmetric with the normal. This was associated
      with a common mesentery and incomplete rotation of the colon, placing the cecum
      under the left lobe of the liver. These alimentary anomalies were discovered in
      adult life during a surgical operation for small intestinal occlusion, as
      evidenced by the abdominal scar and peritoneal adhesions. No cardiac, pulmonary,
      splenic or facial sinus anomalies were encountered. The incidence of complete
      situs inversus is estimated as 1/8000 in the general population. It may be
      isolated or associated with malformations, especially cardiac or alimentary. It
      may be discovered in infancy because of associated anomalies but often remains
      asymptomatic and discovered by chance in adult life. Complete situs inversus may
      form part of the multiple malformational syndromes such as that of Kartagener,
      with recessive autosomal transmission (complete situs inversus, bronchiectasis,
      chronic sinusitis, male infertility), which represents 20-25% of cases of
      complete situs inversus. In view of the frequency of this type of anomaly, a
      knowledge of anomalies of lateralization is essential in clinical practice.

PMID- 11236326
TI  - Variations of the radial artery in man.
AB  - Variations of the radial artery are common in man. A high origin, due either to
      precocious bifurcation or to persistent duplication of the brachial artery, and
      the presence of a superficial dorsal ramus in the forearm suggest hemodynamic
      insufficiency of the axial vascular network allowing persistence of certain
      portions of the superficial system of the upper limb. Confusion of these unusual
      arteries with the subcutaneous veins may explain the accidental injection of
      drugs and distal necrosis of the limb. Knowledge of these variations may
      facilitate ascending catheterization of the cardiac cavities.

PMID- 11236327
TI  - Arterial, neural and muscular variations in the upper limbs of a single cadaver.
AB  - Arterial, neural and muscular variations were observed in both upper limbs of a
      female adult cadaver during routine student dissection. Two superficial radial
      arteries were observed, which originated from the brachial and axillary arteries
      in the left and right upper limbs respectively. In the right upper limb, an ulnar
      nerve with a lateral root from the lateral cord of the brachial plexus in the
      axilla and, in the left forearm, an accessory muscle belly inserting into the
      muscle belly of the flexor digitorum superficialis were also observed. Formation
      of these variations is discussed on the basis of the embryological development of
      the upper limb structures. The clinical importance of the variations is
      emphasized.

PMID- 11236328
TI  - [What the editors wish for the new year].

PMID- 11236329
TI  - [Deinstitutionalization, housing situation and subjective satisfaction of
      schizophrenic patients].
AB  - OBJECTIVE: After the German reunification the deinstitutionalisation of long-term
      hospitalised psychiatric patients and the restructuring of the complementary
      psychiatric care has become necessary in the "new" German states. Hereby it
      became possible to offer alternative residential settings and new community
      oriented care programmes for the mentally disabled. METHODS: Ten years after the
      beginning of this process we analysed the impact of the housing conditions and
      the subjective satisfaction of 245 chronic schizophrenic patients living in
      different residential care-settings or with family resp. on their own in the
      Dresden region. Additionally we asked for the satisfaction with the organisation
      of the deinstitutionalisation process. RESULTS: The subgroups--defined by the
      residential setting--differ in sociodemographic variables and in the levels of
      psychopathology (PANSS) and social disabilities (DAS-M). It is shown how
      deficiencies and restrictions of the living situation and the
      deinstitutionalisation process are reflected in the respective judgments of the
      patients especially referring to autonomy and self-determination. CONCLUSIONS:
      Requirements for the further development of the complementary psychiatric care
      system are deduced.

PMID- 11236330
TI  - [Quality of life of patients with eating disorders. A catamnestic study].
AB  - OBJECTIVE: To assess the eating behaviour, quality of life and changes in life
      style in 46 female patients with eating disorders, discharged from our
      psychosomatic unit at least six month ago. METHODS: Patients meeting the criteria
      for DSM-IV anorexia nervosa or bulimia nervosa completed the "Lancashire Quality
      of Life Profile" [16] and a questionnaire covering demographic aspects, eating
      behaviour and changes in life style. RESULTS: Positive changes in eating
      behaviour correlated with higher quality of life scores in many of the domains
      assessed, including leisure, financial situation and perceived mental health.
      These changes also correlated with positive changes in life style in several
      domains, in particular family situation and leisure activities. CONCLUSIONS:
      Results show that various connections between eating behaviour and quality of
      life as well as life style exist, suggesting a treatment concept that emphasizes
      both clinical symptoms and psycho-social conflicts.

PMID- 11236331
TI  - [Aggressive and suicidal behavior. A cluster analysis study of suicidal and
      nonclinical subjects].
AB  - AIMS: An attempt was made to examine the relationship between different
      dimensions of aggression and suicidal behavior in clinical and non-clinical
      subjects. METHOD: A clinical sample of 68 suicide attempters (39 females, 29
      males) and a matched sample of 70 non-clinical subjects (38 females, 32 males)
      were subgrouped by cluster analytic techniques. Classification variables included
      the scales of the Aggressive Factors Questionnaire (AFQ). Discriminant function
      analyses were performed on the clusters to determine the quality of group
      separation and to assess the power of each input variable. External variables
      such as the amount of hopelessness, suicidal ideation and the number of suicide
      attempts were used to assess the clinical relevance of the identified clusters.
      RESULTS: Two subgroups were identified in each sample. Variables that contributed
      most to group separation were Auto-aggression/Depression and Spontaneous
      Aggression in the non-clinical sample and Excitability in the clinical sample,
      respectively. The clusters identified within the non-clinical sample
      differentiated between ideators and non-ideators. Cluster allocation within the
      clinical sample was indicative of the number of suicide attempts. CONCLUSIONS:
      Clusters defined on the basis of different dimensions of aggressiveness turned
      out to be a classification with significant implications for the assessment of
      suicidal behavior.

PMID- 11236332
TI  - [Hypochondriacal euphoria as a special form of monopolar affective psychosis].
AB  - BACKGROUND: In contemporary concepts of affective psychoses the existence of
      monopolar manias is widely questioned. Nevertheless, cases of manias with
      monomorphous symptomatology are reported repeatedly from all over the world.
      Based upon subtle observation of signs and course over many years, Karl Leonhard
      developed a concept of affective psychoses that permits a distinction of
      monopolar from bipolar forms, e.g. monopolar manias and euphoric euphorias.
      METHODS: As an example for the pure forms of euphorias we present two cases of
      hypochondriacal euphoria. CONCLUSION: We discuss some of the literature relevant
      to the issue and propose the application of a differentiated psychopathological
      analysis for the discrimination of monopolar from bipolar manias.

PMID- 11236333
TI  - ["Agoraphobia--place anxiety/place fear--place-related vertigo". The classical
      description of place anxiety by Carl Westphal and Emil Cordes and its
      significance for the history of the concept and current discussion of anxiety
      disorders].
AB  - We discuss the history of "agoraphobia" and related descriptions as the
      "Platzangst" from M. Benedikt and the artile of E. Cordes, who used the same
      title "agoraphobia" as Westphals original paper. It is remarkable that Westphal
      and Cordes recognized the psychological character of the phenomenon, whereas
      Benedikt in 1870 suspected a neuroophthalmological origin for his
      "Platzschwindel". Regarding the details of these first three descriptions one can
      show that the primary authorities set up a discussion, which is still going on:
      The relation between agoraphobia, dizziness, fear and panic is until now object
      of many controversies, as shown in the final chapter.

PMID- 11236334
TI  - [Psychiatric treatment of prisoners in general psychiatric wards exemplified by
      North Rhine-Westphalia and Rhineland-Pfalz].
AB  - OBJECTIVE: The study was intended to provide information on the frequency and
      general condition of inpatient and outpatient treatment of mentally disturbed
      prisoners in general psychiatry in Germany. METHODS: Directors of psychiatric
      institutions and chief physicians of prisons in Nordrhein-Westfalen and Rheinland
      Pfalz were interviewed via a standardized questionnaire. RESULTS: The use of
      inpatient psychiatric treatment was approximately 0.1 to 2.3% in 1997 with
      reference to the total admissions in 1997. CONCLUSION: The rare use of
      psychiatric beds in general psychiatry may reflect obstacles concerning the
      status of prisoners and reservations regarding difficult patients.

PMID- 11236335
TI  - [Depressive disorders in neurologic rehabilitation: therapy with paroxetine].
AB  - OBJECTIVE: Depression is a common problem in neurological rehabilitation.
      Although three double-blind studies have shown the efficacy of trazodone,
      citalopram and nortriptyline, antidepressant drug therapy of poststroke
      depression is not yet considered a state-of-the-art strategy. In a hospital for
      neurological rehabilitation we have performed an open study on the effects of the
      SSRI, paroxetine, in depressive disorders caused by neurological diseases.
      METHOD: 111 consecutive admissions were screened for depression and 9 patients
      were admitted to the study having a HDRS score > or = 14. RESULTS: 10-40 mg of
      paroxetine were well tolerated and led to a > or = 50% reduction of the HDRS
      score in 8/9 patients. A patient with pathological crying, but without
      depression, was also successfully treated with 20 mg of paroxetine. CONCLUSIONS:
      We conclude that the SSRI, paroxetine, is an effective and well-tolerated therapy
      of depressive disorders caused by various neurological diseases, including also
      other diagnoses than stroke.

PMID- 11236336
TI  - [Abdominal pain syndrome as the chief symptom of an anxiety and depressive
      disorder. Successful treatment with inpatient psychotherapy].
AB  - OBJECTIVE: Though frequently misinterpreted, gastrointestinal complaints are
      among the most common psychosomatic syndromes. CASE REPORT: The following report
      describes the case-history of a 60-year old woman, hospitalized for recurrent
      abdominal pain and diarrhoea. During the course of parallel internal and
      psychosomatic examinations an organic cause could be excluded and the
      psychogenesis of the complaints identified. RESULTS: Once the diagnosis of a
      somatoform disorder had been established the symptoms were successfully treated
      within the framework of in-patient psychotherapy. CONCLUSIONS: Anxiety and
      depressive disorder are often masked as abdominal pain. If detected, they can be
      successfully treated using a psychotherapeutic approach. Thus this article also
      points to the great importance of the availability of a psychosomatic
      consultation-liaison-service within general hospitals.

PMID- 11236337
TI  - [Carbamazepine-induced SIADH with clinical signs of delirium].

PMID- 11236338
TI  - [Multicenter study on the effectiveness of Tension Vaginal Tape (TVT) in the
      treatment of stress urinary incontinence].
AB  - BACKGROUND: The aim of the study was to evaluate the efficacy of Tension Free
      Vaginal Tape (TVT) for the surgical treatment of stress urinary incontinence.
      METHODS: The design was an open multicenter study including six Italian
      hospitals. Between January 1998 and November 1999, 429 stress incontinent women
      were enrolled in the study. Before surgery subjects had been studied through
      their history, urine culture, physical examination, cotton swab test, cough
      provocation test and urodynamic evaluation including: uroflowmetry, water
      cystometry and urethral profilometry. Incontinence inconvenience has been
      quantified through a 10-grade visual analogue scale (VAS). Postoperatively
      patients were assessed after 6, 12 and 24 months. RESULTS: The mean age of the
      patients considered was 57 years (range 31-83) and 78 of them had undergone a
      previous operation for the treatment of stress urinary incontinence or genital
      prolapse. Out of the 429 patients, 371 were followed for a minimum of 6 months,
      11 were lost to follow-up and 47 had been operated recently. After surgery 355
      subjects (96%) were subjectively cured and no leakage of urine was observed in
      97% of the patients during the postoperative cough provocation test. CONCLUSIONS:
      This study carried out on a great number of patients demonstrates that TVT is a
      safe and effective procedure for the treatment of stress urinary incontinence.

PMID- 11236339
TI  - [Pregnancy management in women with thalassemia].
AB  - Thanks to the improvement of the techniques of assisted fecundation, of the
      obstetric management and of the fetal and neonatal monitoring now it's possible
      for a woman suffering from beta-thalassemia to have a child. Our purpose is to
      stress the importance to control the high maternal and fetal risk through the
      monitoring of several scales. The problems, connected with pregnancy of beta
      thalassemic women are discussed, emphasizing the connection between pregnancy
      management and gestational and neonatal outcome. A variety of problems should be
      considered such as the informed consent about maternal and fetal risks, the
      problems caused by infectious agents or due to the use of some antiviral; the
      difficulties connected with heart and endocrine diseases are also discussed.
      Personal experience, from 1995 to 1999, on 4 beta-thalassemic pregnant women
      (three with the intermediate type and one with the major type) is reported.

PMID- 11236340
TI  - [Antibiotic prophylaxis of infective complications after cesarean section. Our
      experience].
AB  - BACKGROUND: The efficacy of a single dose of antibiotic vs multiple doses of the
      same drug, in reducing maternal infections following the cesarean section, is
      evaluated. METHODS: A total of 206 pregnant women undergoing elective or
      emergency cesarean section from 1st June 1998 to 30 June 1999, at the Department
      of Obstetrics and Gynecology of the University of L'Aquila, were included in a
      randomized study to compare the efficacy of prophylaxis with a single dose of
      piperacillin sodium (2 g i.v. after the umbilical cord clamping; group A) vs
      triple doses of the same antibiotic (2 g i.v. at 6 hourly intervals, beginning
      from the umbilical cord clamping; group B). RESULTS: The incidence of infective
      morbidity in group A was 7.3%, with a 2% wound infections, 1% urinary infections
      and 4.16% febrile morbidity. The incidence of infective morbidity in group B was
      not much higher (9%), with 2.7% wound infections, 1.8% urinary infections and
      4.5% febrile morbidity. CONCLUSIONS: In order to obtain a useful antibiotic
      prophylaxis in cesarean sections, the single-dose seems to be preferable to the
      multiple-doses, since the single-dose not only has equal efficacy, but also less
      cost, smaller risk of super-infections by resistant organisms and it involves
      smaller care from the-medical and nursing staff.

PMID- 11236341
TI  - [Gynecologic tumors].

PMID- 11236342
TI  - [Sequential endo-laparoscopic treatment in patients with common bile calculi].
AB  - BACKGROUND: Laparoscopic treatment of common bile duct (CBD) stones is gaining
      great acceptance worldwide, but actually it requires skills and technologies too
      expensive for a great part of general surgeons. So endoscopic removal of CBD
      stones before cholecystectomy is usually performed. Since 1991 in our department
      we started a policy of selective preoperative cholangiopancreatography (ERCP) in
      patients suspected for choledocholithiasis and waiting for laparoscopic
      cholecystectomy. METHODS: A retrospective study has been made on a population of
      1100 patients who underwent elective laparoscopic cholecystectomy in the period
      between January 1991 and December 1997. They were 391 male and 719 female with a
      mean age of 52 years, 126 of whom (11.5%) were selected to have ERCP
      preoperatively because they had clinical, biochemical and ultrasound signs of the
      presence of common bile duct stones (CBDS). RESULTS: Successful cannulation of
      the CBD was achieved in 124 cases (98.4%), with failures due to ampullary
      diverticula. In 7 cases (5.5%) a precut was necessary to obtain cannulation.
      Sphincterotomy was performed in 113 patients (89.7%). In 93 patients (73.8%)
      stones were found (87 macrolithiasis and 6 microlithiasis); in 91 (97.8%) stones
      were removed in one (87) or two (4) endoscopic session. There were 2 major
      complications (one bleeding and one severe pancreatitis) due to ERCP or a
      sphincterotomy. Two patients developed symptoms from unsuspected common bile duct
      stones after LC and were removed endoscopically. No complications during LC were
      due to ERCP or ES. CONCLUSIONS: Selective preoperative ERCP is an effective way
      of clearing the CBD stones before laparoscopic cholecystectomy, with low rate of
      complications related to endoscopic and laparoscopic procedures, and short mean
      hospital stay (5.5 days), according to the concept of minimally invasive
      treatment.

PMID- 11236343
TI  - [Evolution of the technique and indications of mini-invasive surgery of
      cholelithiasis].
AB  - BACKGROUND: A review of the experience with laparoscopic cholecystectomy to
      evaluate the impact of the efficacy, safety, and complications on the learning
      curve. STUDY DESIGN: Retrospective study. METHODS: Between 1993 and 1998, 415
      patients, 123 males and 292 females, median age 52.1 years (range 23-96 years),
      with symptomatic cholelithiasis, underwent laparoscopic cholecystectomy. On the
      basis of different selection criteria and surgical techniques adopted, our
      experience was divided into two periods (93-95 and 96-98). RESULTS: The success
      rate was 89.4% (371 patients) with a conversion rate of 10.6% (44 patients).
      Overall complications rate was 2.9% (12 patients): 7 major complications (2
      biliary tract injuries, 2 hemorrhages, 1 sub-phrenic abscess, 1 gastric
      perforation and 1 choleperitoneum) and 3 minor complications (1 biliary leakage
      and 2 wound infections) with 2 long-term sequela (umbilical site eventration).
      Median hospital stay was 3.3 days, 2.2 days for uncomplicated cases and 5.6 in
      those converted or complicated. Comparison between the two groups showed a
      conversion rate of 10.6 vs 10.4% (23 vs 21 patients), with a complication rate of
      4.2% vs 2.2%. CONCLUSIONS: Laparoscopic cholecystectomy can be considered a safe
      and effective procedure for the treatment of simple or complicated
      cholelithiasis. French surgical technique seems to be easier in the management of
      acute cholecystitis or lithiasis occurring after acute pancreatitis. Specific
      training in laparoscopy surgery is mandatory to avoid major complications.

PMID- 11236345
TI  - [From surgical gloves to the rat. The various stages of microsurgery learning].
AB  - The paper describes the different stages of microsurgical training which should
      be followed in an experimental laboratory; it also stresses the main
      characteristics to which microsurgical trainees must pay attention without
      neglecting any steps, even the most banal ones, because microsurgery is a
      sequence of exercises and not a single one (microsuture). The rigorous and
      increasingly difficult step-by-step progress of the different phases allows the
      trainee to face the different passages with greater ability and mastery without
      losing that enthusiasm which is the motivating force. Obstacles and failures can
      be evaluated with a more critical and reflective eye. Microsurgical training
      foresees the gradual passage from synthetic materials, such as surgical gloves,
      to non-living biological structures, such as chicken legs, finishing with
      experimental animals such as the rat. These biological models are almost
      identical to human structures making the experimental stage very similar to
      direct clinical application. Microsurgery, nowadays, is an integral part of all
      surgical disciplines. A correct approach to surgery using a microscope, according
      to this teaching scheme, is surely of great help not only for young surgeons but
      for the veterans of surgery too.

PMID- 11236344
TI  - [Short-stay surgery of inguino-crural hernia].
AB  - BACKGROUND: To evaluate the hospital stay, morbidity, and patients' compliance
      for short stay inguinal hernia repair. METHODS: Retrospective analysis of 669
      patients (594 men and 75 women) who underwent short stay inguinal hernia repair
      (706 inguinal and 45 femoral repairs) at the Institute of General Surgery,
      University of Ferrara. Mean age was 60.7 years (range, 18-84 years). The
      anesthesia was: loco-regional in 495 patients (74%) and general or epidural in
      174 (26%). RESULTS: Mean hospital stay was 1.2 days. Postoperative complications
      were: three scrotal hematomas, two ischemic orchitis, three prosthetic
      infections, one local anesthetic intolerance, and three high fever. Eighty-five
      percent of patients were satisfied of the surgical procedure in short hospital
      stay. Mean follow-up was 36 months. CONCLUSIONS: Short hospital stay in inguinal
      hernia repair is safe, effective, and widely accepted by patients.

PMID- 11236346
TI  - [Incidence of complications of thyroid surgery].
AB  - BACKGROUND: Thyroid surgery presents a low incidence of complications. Death is
      certainly a rare, or even exceptional event. Hypoparathyroidism, above all if
      definitive, is the main complication of total thyroidectomy with percentages that
      very between 0 and 10% in the literature (average 2%). METHODS: The incidence of
      recurrent lesions varies between an improbable 0% to 8%, whereas lesions to the
      superior laryngeal nerve are relatively frequent, but often undervalued.
      Dysphagia, although always transient, presents a high risk of pneumonia ab
      ingestis and severe dehydration. Hemorrhage has an incidence of 0.1-3.8% and
      infection is reported in approximately 1% of cases. The permanent and recurrence
      nature of thyroid pathology in literature is between 5 and 11%, resulting from
      inadequate or sometimes useless surgery. Hypothyroidism is the logical
      consequence of total thyroidectomy. In the light of these data we have re
      examined 300 operations involving thyroid pathology performed by the same team
      using the same method over the past 4 years (82% females, 18% males). 33% of the
      cases presented benign euthyroid nodular pathology, 27% hyperfunctioning benign
      nodular pathology, 2.6% Flajani-Basedow-Graves disease, 9% were adenomas, 7% were
      differentiated carcinomas, 2% anaplastic carcinomas and 0.7% medullary
      carcinomas. 99 extracapsular total loboisthmectomies, 135 total extracapsular
      thyroidectomies and 66 subtotal thyroidectomies were performed. RESULTS: The
      following complications were observed: 31/300 symptomatic hypocalcemias of which
      25 were transient and 6 (2%) were definitive but easily controlled with
      treatment; 9 recurrent monoplegias out of 501 isolated recurrent forms of which 4
      (0.8%) was permanent; 5/300 (1.7%) postoperative dysphagias associated with
      recurrent monoplegia in 4 cases. Damage to the external branch of the superior
      laryngeal nerve was suspected in 11/300 cases (3.7%). Postoperative hemorrhage
      occurred with an incidence of 1.3%, whereas the incidence of wound infection and
      serous collection was 1.7%. Moreover, persistent hyperthyroidism after subtotal
      bilateral thyroidectomy was observed secondary to toxic plurinodular struma. A
      case of paralysis of the right ulnar nerve, when the arm was adducted, was
      observed on the operating table, but regressed after about 4 months. Mortality
      was zero. CONCLUSIONS: Thyroid surgery is still hampered by a relatively low
      percentage of complications, which are probably still the result of various
      technical limitations, and it appears difficult to reduce these, let alone
      eliminate them completely.

PMID- 11236347
TI  - [Congenital anomalies of the inferior vena cava].
AB  - Congenital anomalies of the inferior vena cava are a relatively rare pathology,
      usually with an asymptomatic iter. They are usually diagnosed by chance during
      surgery on the aorta or retroperitoneal structures. From bioptic material their
      incidence is estimated to be 2-3% and the percentage of intraoperative findings
      varies in different series between 0.2 and 0.6%. Of the various kinds of anomaly,
      caval duplication and a left-positioned vena cava are those most commonly found.
      The recent report of a case of a malpositioned vena cava and iliac veins prompted
      us to re-examine the literature and revise our series of cases.

PMID- 11236348
TI  - Donor and recipient postoperative complications in living related kidney
      transplantation. A multicentric study.
AB  - BACKGROUND: Living related kidney transplantation is considered a gold standard
      of renal transplantation in order to overcome end-stage renal disease within the
      same family members. Living donation, albeit decreasing cadaveric donor shortage,
      exposes donors to the risk of surgical complications. METHODS: In order to assess
      the postoperative complication rate in donors and recipients, we reviewed
      retrospectively 90 consecutive living related kidney transplants in a
      multicentric study. All nephrectomies were performed extraperitoneally through a
      left flank incision. RESULTS: Major perioperative complications (first 3 weeks
      after surgery) occurred in 12 subjects: these included bleeding (2.2%),
      symptomatic pneumothorax (1.1%), iliac thrombophlebitis (3.3%), iliac artery
      dissection (1.1%), laparotomic dehiscence (2.2%), perirenal hematoma (1.1%),
      renal artery stenosis (1.1%), urinary fistula (1.1%). Minor perioperative
      complications took place in 8 cases. One recipient died. Donor postoperative
      major complications occurred in 2 subjects. CONCLUSIONS: On the basis of these
      results we conclude that living related kidney transplantation is an important
      treatment of end stage renal disease, due to the associated low major
      complication rate and the high feasibility of this methodology.

PMID- 11236349
TI  - [Nosocomial infections. State of the art].
AB  - Little information exists up till now about the prevalence of nosocomial and
      community acquired infections in Italian hospitals. Little is known about the
      effects of thorough cleaning in today's hospitals. This review examines the
      common microorganisms associated with hospital acquired infections and their
      ability to survive in the hospital environment. The most frequent site of
      hospital acquired infections is the urinary tract, followed by surgical wounds
      and the upper respiratory tract. Analysis of North America and European data
      shows that the increase in length of stay for infected patients is the most
      striking of all examined costs. Improving standards of hygiene in hospitals would
      be a safe method to control hospital-acquired infections and their costs.

PMID- 11236351
TI  - [Substitution therapy in alpha 1-antitrypsin deficiency].

PMID- 11236350
TI  - [Mesogastrectomy in the surgical treatment of gastric carcinoma. Experience with
      61 cases].
AB  - BACKGROUND: In gastric cancer surgery, to search for a technique to remove the
      entire posterior mesogastric region using a standardised operation using well
      defined methods and anatomic-embryological planes. METHODS: A concise description
      of the embryological evolution of the posterior mesogastrium allow the formation
      of the mesogastric fascia (and the supramesocolic fascia of the omentum--which is
      a continuation) to be documented. It is also clear that the mesogastric fascia is
      the embryological--anatomical equivalent of Treitz's fascia, pancreatic retro
      head, and Toldt's retrocolic fascia, of which it is a structural continuation.
      Like Treitz's and Toldt's fascias, the mesogastric fascia also represents the
      surgical plane for the detachment of the region in question and allows maximum
      safety and radicality. By carrying out primary ligature of the arteries at the
      origin and the veins at the outlet, the entire posterior mesogastric region, with
      the relative lymph node stations, can be removed en bloc with maximum radicality
      and safety, and also in line with the principle of "no touch isolation". We used
      this technique to operate 61 cases, 17% of all cases of gastric carcinomas
      between 1973 and 1994. RESULTS: Mesogastrectomy was required in 87% of cases with
      carcinoma in a high localisation or widespread nature of the linitis plastica
      type. Only 23 cases (37%) were at pTNM II and III A stages. Thirty-eight cases
      (63%) were at stages III B and IV. In non-selected cases and those with severe
      associated pathologies and undergoing emergency surgery, and those cases that
      were extended beyond mesogastrectomy, morbidity was above all linked to pleural
      effusion. There were only 2 cases (3%) of operating mortality owing to two
      technical errors: an esophago-jejunal anastomotic dehiscence (the only case in
      the series, 1.6%) caused by esophageal cancer nests in the suture and a case of
      necrosis in the left hepatic region following the section of the left gastric
      artery at the origin despite the existence of a large hepatic collateral vessel.
      The results for stages II and III A were excellent: stage II, 100% survival at 5,
      10 and 15 years; stage III A 88% survival at 5 years, 70% at 10 years, 55% at 15
      years, but only two deaths from neoplasia at 2.7 and 4.6 years. The results for
      stages III B and IV are comparable to large series undergoing traditional forms
      of surgery. Postoperative conditions of nutrition and quality of life were good
      and patients resumed activities with the aid of constant chlorhydric-peptic
      replacement treatment and the total extraction of gastric mucosa. CONCLUSIONS: We
      believe that mesogastrectomy represents a real advance in both technical terms
      and results for stages II and III A; it is debatable for stages III B and IV,
      although individual cases who survived for more than 10 years were also reported.
      The case of a stage pT3N0M1 = IV pathology, with a single hepatic metastasis that
      increased until one year and then spontaneously resolved leaving the patient
      alive and in good health 20 years and 6 months after the operation is truly
      amazing.

PMID- 11236352
TI  - [Heart failure and central respiratory dysregulation. Cheyne-Stokes respiration
      during sleep in advanced left heart failure].
AB  - Central sleep apnoea, especially Cheyne-Stokes respiration, is found in 45 to 66%
      of patients with congestive heart failure (CHF) in functional classes NYHA II to
      IV. Cheyne-Stokes breathing cycles are characterised by central apnoeas, followed
      by a crescendo--like increase of tidal volume into hyperventilation and a
      subsequent decline of tidal volume, ending in another central apnoea. Cheyne
      Stokes respiration has been shown to be a poor prognostic factor for patients
      with CHF. Apnoeas and hypopnoeas cause marked oxygen desaturation and rises of
      carbon dioxide concentrations in the blood. The resumption of breathing is
      frequently associated with arousals, which might cause daytime symptoms like
      fatigue and sleepiness as well as persistent activation of the sympathetic
      nervous system. Elevated concentrations of catecholamines increase cardiac work,
      adversely affecting cardiac function. Serum catecholamines are known to augment
      the chemoreceptor susceptibility for carbon dioxide. This might be one reason for
      the permanent mild hyperventilation found in these patients during wakefulness.
      Increased chemoreceptor responsiveness destabilises the feedback control of
      breathing, and hyperventilation below the apnoeic threshold grows more likely.
      Other contributing factors for the development of Cheyne-Stokes respiration
      include alterations in the control of breathing during sleep and the increased
      circulation time between the lung and chemoreceptors in CHF patients. The
      feedback regulation of breathing might be less dampened since carbon dioxide
      levels are reduced in these patients. Treatment includes nCPAP, but in many cases
      this is poorly tolerated in patients with central sleep apnoea. Future approaches
      to Cheyne-Stokes respiration might focus on improving ventilatory pattern and
      pharmacological manipulation of carbon dioxide receptor susceptibility.

PMID- 11236353
TI  - [Noninvasive positive pressure ventilation in acute respiratory insufficiency--a
      report of the International Consensus Conference in Internal Medicine, Paris 13
      14 April 2000].

PMID- 11236354
TI  - [Effect of surgical positioning and spinal anesthesia on lung function].
AB  - BACKGROUND: Various surgical positions, e.g., lithotomy, prone, or head-down
      positions influence respiratory mechanics. The aim of the present paper was to
      investigate whether particular surgical positions (lithotomy, lithotomy with head
      down tilt, prone, prone with a roller placed under the abdomen) as well as spinal
      anaesthesia in lithotomy position impair the pulmonary function to a greater
      extent than supine position and whether they have to be considered as increasing
      the perioperative risk in elderly patients and patients with ventilatory
      disorders. METHODS: In two separate experimental series, we examined a) the
      influence of the surgical positions on the pulmonary function in 45 subjects (25
      without and 20 with ventilatory disorders) and b) the effects of spinal
      anaesthesia in 25 urologic patients (9 without and 16 with ventilatory
      disorders). Static and dynamic lung function parameters were determined. Under
      spinal anaesthesia, the arterial O2 saturation and the end-expiratory partial
      pressure of CO2 were measured additionally. RESULTS: The most pronounced lung
      function decrease occurred with the transition from seated to supine position.
      Lithotomy and prone positions impaired the respiratory function only slightly. In
      elderly persons and in patients with ventilatory disorders, the spirometric
      changes tended to be stronger than in young persons, but were not considered to
      increase the perioperative pulmonary risk. A combination of lithotomy position
      and spinal anaesthesia did likewise not remarkably impair the respiratory
      function. CONCLUSIONS: Lithotomy and prone positions as well as spinal
      anaesthesia are not considered to be an additional risk factor for pulmonary
      function.

PMID- 11236355
TI  - [Long-term treatment of primary pulmonary hypertension with inhaled iloprost].
AB  - BACKGROUND: Continuous intravenous infusion of prostacyclin is an effective
      treatment for primary pulmonary hypertension. This approach, however, requires
      the insertion of a permanent central venous catheter with the potential risk of
      serious complications. Recently, administration of aerosolized iloprost, a stable
      prostacyclin analogue, has been introduced as an alternative therapy for severe
      pulmonary hypertension. METHODS: We evaluated the effects of treatment with
      aerosolized iloprost over a one-year period on exercise capacity and hemodynamic
      variables in patients with primary pulmonary hypertension. RESULTS: Twenty-four
      patients with primary pulmonary hypertension received aerosolized iloprost at a
      cumulative daily dose of 100 to 150 micrograms for at least one year. The mean
      (+/- SD) walking distance in the 6-min-walk test increased from 278 +/- 96 meters
      at base line to 363 +/- 135 meters after 12 months (P < 0.0001). During the same
      period, the mean pulmonary artery pressure declined from 59 +/- 10 mmHg to 52 +/-
      15 mmHg (P = 0.006), the cardiac output increased from 3.8 +/- 1.4 l/min to 4.4
      +/- 1.3 l/min (P = 0.02), and the pulmonary vascular resistance declined from
      1.205 +/- 467 dynes.s.cm-5 to 925 +/- 469 dynes.s.cm-5 (P = 0.0003). Treatment
      was generally well tolerated and except for mild coughing, minor headache and jaw
      pain in some patients, no side effects occurred. CONCLUSIONS: Long-term treatment
      with aerosolized iloprost is safe and has sustained effects on exercise capacity
      and pulmonary hemodynamics in patients with primary pulmonary hypertension.

PMID- 11236356
TI  - [Evaluating oronasal flow with temperature (thermistor) and obstructive pressure
      (prongs)].
AB  - The measurement of oronasal flow during sleep studies using thermistors is
      internationally well accepted. As an alternative the possibility exists to
      measure the pressure at the nose by means of nasal prongs. Our objective was to
      compare and evaluate the methods to detect respiratory events in clinical
      routine, namely O2-saturation by pulse oxymetry oronasal flow by thermistors
      thoraco-abdominal effort by belts oronasal flow by prongs, 8 consecutive patients
      suspected of sleep apnoea syndrome (7 m, 1 f), mean age 56.5 +/- 9.5 years,
      height 173 +/- 6.4 cm, BMI 28.7 +/- 2.6 kg/m2, Epworth sleepiness scale score 9.1
      +/- 3.2, AHI 24.9 +/- 13.7 h-1, lowest SaO2 86 +/- 4.9%, were examined. Between
      nose and mouth we fixed an oronasal 3-point thermistor and oronasal prongs (2
      openings at the mouth and 2 openings at the mouth applying a common tube). During
      breathing the resulting pressure was registered with a pressure transducer
      parallel to the signal of the thermistors and the other polysomnographic data. We
      defined a respiratory event if at least one of the 4 signals met the criteria of
      a respiratory disturbance (for exact definitions see method). The detection rate
      of the 4 signals was calculated in relation to the sum of all events. Of the 1824
      events (100%) only 52.3% were detected by an O2-desaturation of more than 4%, but
      61.0% by thermistors. An acceptable detection rate was found measuring effort
      with 83.4%, only nasal prongs detected 95.1% of all events. We conclude that with
      regard to the detection rate of respiratory events the measurement of pressure by
      nasal prongs is superior to the use of thermistors.

PMID- 11236358
TI  - [Dissemination and acceptance of recommendations of the German Respiratory League
      on asthma therapy in children and adults].

PMID- 11236357
TI  - [Heparin-induced type II thrombocytopenia as the etiology of severe recurrent
      pulmonary embolism].
AB  - Heparin-induced thrombocytopenia (HIT) is a rare complication of anticoagulative
      heparin therapy. The more severe HIT type II is defined by peripheral
      thrombocytopenia combined with thrombotic and thromboembolic events. We report
      the case of a 24 year old male patient who was admitted to our ICU with
      thromboembolic obstruction of the right central pulmonary artery, and deep venous
      thrombosis (DVT) of the right superficial femoral vein. Systemic thrombolytic
      therapy with urokinase for seven days resulted in nearly complete resolution of
      the thromboembolic material in the pulmonary arteries. Antithrombotic therapy
      with intravenous heparin and overlapping oral phenoprocoumon was continued on the
      regular ward. Six days later, the patient had to be readmitted to the ICU with
      evidence of hemodynamic compromise due to massive bilateral pulmonary
      thromboembolism that could be confirmed by CT scan--DVT had extended to the right
      iliacal vein. Additionally, peripheral thrombocyte counts had markedly declined
      from 112.000 to 35.000/microliter within 3 days, indicating the presence of a Hit
      type II. This was verified by positive ELISA testing for antibodies against
      platelet factor 4 (PF4)-heparin-complex. A filter device was temporarily
      implanted into the inferior vena cava. The patients condition stabilized upon
      reinitiated systemic thrombolysis and replacement of heparin therapy against
      recombinant hirudin. Pulmonary artery pressures normalized. Peripheral
      thrombocytopenia diminished within three days. HIT type II is a severe
      complication of anticoagulative therapy with heparin. Here we report a case, and
      discuss diagnostic procedures as well as differential diagnosis to HIT type I.

PMID- 11236359
TI  - [Patient-ventilator interaction during noninvasive pressure supported spontaneous
      respiration in patients with hypercapnic COPD].
AB  - BACKGROUND: Noninvasive pressure support ventilation (NPSV) demands triggering
      with each breath. This study investigates the effects of NPSV via face mask on
      breathing pattern, ventilation and respiratory muscle loading in patients with
      hypercapnic stable COPD. METHODS: 7 patients (age 66 +/- 9 years; FEV1 43 +/- 13%
      predicted; PaO2 52 +/- 19 mmHg; PaCO2 58 +/- 12 mmHg) were included. The
      physiologic variables were evaluated during spontaneous breathing and at the end
      of a 60 minutes period with NPSV. Inspiratory positive airway pressure (IPAP) and
      expiratory positive airway pressure (EPAP) were adjusted to 12-14 cm H2O and 3 cm
      H2O, respectively. Respiratory muscle activity was measured as esophageal and
      transdiaphragmatic pressure time product (PTPes and PTPdi). RESULTS: Non
      triggering was observed only occasionally. Compared to unsupported spontaneous
      breathing NPSV improved ventilation: PaCO2 was reduced from 58 +/- 11 mmHg to 50
      +/- 14 mmHg (p +/- 0.05). Respiratory muscles were unloaded by 30% (p +/- 0.05).
      Breathing frequency and breathing pattern did not change. CONCLUSIONS: In
      patients with hypercapnic stable COPD NPSV effectively recognizes and supports
      breathing efforts. As a result ventilation is improved and respiratory muscles
      are unloaded.

PMID- 11236360
TI  - Standardized nursing vocabularies: a foundation for quality care.
AB  - OBJECTIVES: To describe the importance of standardized nursing vocabularies as a
      foundation for quality in health care decision-making. DATA SOURCES: Literature,
      online sources, and committee documents. CONCLUSIONS: Several standardized
      vocabularies are recognized by the American Nurses Association Committee for
      Nursing Practice Information Infrastructure. Vendors also have integrated the
      vocabularies into their information systems. Future efforts include developing an
      international nursing reference terminology. IMPLICATIONS FOR NURSING PRACTICE:
      Oncology nurses face quality of care issues that impact decision-making at the
      point of care. To describe their practice, oncology nurses must strive to use
      nursing data that are standardized, documented, and made visible by inclusion in
      computer-based systems.

PMID- 11236361
TI  - Health informatics and oncology nursing.
AB  - OBJECTIVES: To provide an overview of the essential role of health and nursing
      informatics in meeting the 21st century call to provide state-of-the-art oncology
      care. DATA SOURCES: Published articles, research studies, and documents relating
      to informatics. CONCLUSIONS: Health and nursing informatics encompass the pivotal
      roles of data and information; identifying and documenting essential data using
      nursing vocabularies; ensuring adequate computer-based patient record systems;
      accessing and building knowledge; using telecommunications to support care
      delivery; empowering the consumer through health informatics; transforming
      education; and enhancing decision making in oncology nursing through national
      research agendas. IMPLICATIONS FOR NURSING PRACTICE: The information age calls us
      to explore digital and information technologies as extensions of human capacity.
      Oncology nursing practice is especially positioned to contribute to the health of
      our population.

PMID- 11236362
TI  - Computer-based patient record systems.
AB  - OBJECTIVES: To provide oncology nurses with an overview of computer-based patient
      record (CPR) systems, a key infrastructure requirement in information management
      that is essential to maintaining a scientific basis for health care. DATA
      SOURCES: Published articles, research studies, and review articles pertaining to
      CPR systems. CONCLUSIONS: Progress in hardware development, software
      applications, and interfaces combine to bring us multimedia patient record
      systems. Many obstacles have been overcome as standards have emerged and
      technologies conform to those standards. However, there has been limited success
      in implementation of such systems. Early acceptance of structured data and
      problem-oriented documentation set the framework for charting in the electronic
      record. IMPLICATIONS FOR NURSING PRACTICE: Oncology clinicians and cancer
      patients alike will realize greater efficiencies and increased quality in health
      care when the CPR is fully implemented.

PMID- 11236364
TI  - The potential of consumer health informatics.
AB  - OBJECTIVES: To describe the rapidly evolving field of consumer health informatics
      (CHI), which is empowering the patient and the public. DATA SOURCES: Published
      articles, research studies, and government reports pertaining to interactive
      health communication and CHI. CONCLUSIONS: Application of CHI can provide
      information to patients and the public, promote self-care, enable informed
      decision-making, promote healthy behaviors, and promote peer information exchange
      and social support. Quality, research methodology, and accessibility must all be
      increased to ensure that CHI achieves its potential to improve the nation's
      health. IMPLICATIONS FOR NURSING PRACTICE: With the advent of the internet, the
      profusion of consumer health-related web sites, online support groups, and
      electronic patient-centered communications present new challenges for clinical
      practice. Health care providers have important roles in helping their patients as
      well as the public locate, assess, and interpret health information.

PMID- 11236363
TI  - Telehealth: a new venue for health care delivery.
AB  - OBJECTIVES: To inform oncology nurses about how telehealth technologies have
      changed the way in which health care is delivered. DATA SOURCES: Published
      articles, research studies, and review articles pertaining to telemedicine,
      telenursing, and telehealth. CONCLUSIONS: Telehealth technologies connect health
      professionals and patients worldwide, facilitating consultations among
      professionals, diagnosing and assessing disease, interviewing, history taking,
      and prescribing therapy and medication. New telehealth projects connecting
      providers and patients are emerging rapidly. IMPLICATIONS FOR NURSING PRACTICE:
      Oncology nurses are prime candidates to transport their expertise to patients and
      other providers via telehealth technologies.

PMID- 11236365
TI  - Distance learning in nursing.
AB  - OBJECTIVES: To inform oncology nurses about distance-learning technologies and to
      offer suggestions for how nurses can locate, appropriately select, and use
      distance learning to their benefit. DATA SOURCES: Published articles, research
      studies, and review articles pertaining to distance education and learning in
      nursing. CONCLUSIONS: Distance learning offers new opportunities for nurses who
      are seeking basic or advanced degrees, certificates, or lifelong learning for
      professional development. IMPLICATIONS FOR NURSING PRACTICE: Oncology nursing
      practice is a dynamic specialty and requires the nurse to be a lifelong learner.
      Distance learning facilitates this requirement.

PMID- 11236366
TI  - The Cancer Informatics Infrastructure: a new initiative of the National Cancer
      Institute.
AB  - OBJECTIVES: To inform oncology nurses about the National Cancer Institute (NCI)
      Cancer Informatics Infrastructure initiative that will transform cancer care
      through more effective and efficient information exchanges among all involved in
      cancer research. DATA SOURCES: Published articles and reports from the NCI
      pertaining to the initiative. CONCLUSIONS: Clinical trials represent the primary
      mechanism for evaluating promising new strategies to prevent, diagnose, and treat
      cancer. Advances in information technology and the exponential increase in the
      use of the internet are providing unprecedented opportunities to streamline the
      operation and administration of the clinical trials the NCI supports.
      IMPLICATIONS FOR NURSING PRACTICE: The revitalized system will be more flexible
      and inclusive and will facilitate input from oncology nurses and others with a
      commitment to improving cancer care.

PMID- 11236367
TI  - Electronic access to scientific nursing knowledge: the Virginia Henderson
      International Nursing Library.
AB  - OBJECTIVES: To inform oncology nurses about the electronic knowledge resources
      offered by the Sigma Theta Tau International Virginia Henderson International
      Nursing Library. DATA SOURCES: Published articles and research studies.
      CONCLUSIONS: Clinical nursing research dissemination has been seriously affected
      by publication bias. The Virginia Henderson International Nursing Library has
      introduced both a new publishing paradigm for research and a new knowledge
      indexing strategy for improving electronic access to research knowledge
      (findings). IMPLICATIONS FOR NURSING PRACTICE: The ability of oncology nursing to
      evolve, as an evidence-based practice, is largely dependent on access to research
      findings.

PMID- 11236368
TI  - The Internet in oncology nursing.
AB  - OBJECTIVES: To explore the implications of the internet for oncology nursing
      practice, education, and research. DATA SOURCES: Published articles, texts,
      research studies, review articles, and online documents pertaining to the
      internet. CONCLUSIONS: The internet has influenced nearly every aspect of
      society. As the worldwide communications infrastructure strengthens, access
      devices become affordable, and more countries contribute content in their native
      language, this technology becomes a truly global phenomenon. This affords
      oncology nursing a voice that extends beyond the community support group to
      millions of internet users. IMPLICATIONS FOR NURSING PRACTICE: Internet access,
      quality of information, and privacy of data transmitted are among the greatest
      challenges that face oncology nurses who integrate this technology into practice.

PMID- 11236369
TI  - [Muscle weakness or rigidity due to hereditary ion channel diseases].
AB  - Three men, aged 36, 16 and 66 years, had suffered for several years from muscular
      weakness; after a low serum potassium level had been established, supplementary
      examination revealed hypokalaemic periodic paralysis. A woman aged 25 had
      suffered since youth from muscular stiffness on sudden movements; she suffered
      from hereditary myotonia of the recessive type (Becker's disease). Both rare
      skeletal muscle ion channel diseases are characterized by the fact that the
      variable clinical expression complicates making the diagnosis. Since the causal
      mutations are known, genetic analysis is an essential step in confirming the
      diagnosis. Additional EMG procedures may be of diagnostic value, even in cases
      that cannot be clarified genetically.

PMID- 11236370
TI  - [Effects of second and third generation oral contraceptives on hemostasis].
AB  - Use of oral contraceptives induce changes in haemostatic parameters: changes
      occur in the procoagulant, anticoagulant, and fibrinolytic systems. The increased
      risk of venous thromboembolism with use of third, as compared with second
      generation oral contraceptives, found in epidemiological studies, has stimulated
      new research in haemostatic changes induced by both generations of oral
      contraceptives. A randomized crossover study showed that use of the third
      generation pill caused a greater increase of factor VII and prothrombin and a
      more pronounced decrease of factor V than the second generation pill. Acquired
      resistance to activated protein C (APC) was induced more strongly by preparations
      of the third than by those of the second generation. The concentration of protein
      S decreased markedly exclusively during use of the third generation pill, while
      it did not change during use of the second generation pill. The oral
      contraception-related effects on the anticoagulant system strongly resemble those
      of some forms of hereditary thrombophilia. If a woman with hereditary APC
      resistance (caused by factor V Leiden) uses oral contraceptives as well, and
      especially when she uses those of the third generation, she is subject to a
      considerable increase of the risk of venous thrombosis and becomes even more
      resistant to the anticoagulant action of protein C. In view of the
      epidemiological backgrounds of the difference in risk of thrombosis between
      second and third generation contraceptives, the second generation pill is
      recommended as the first choice for oral contraception.

PMID- 11236371
TI  - [Solvent-induced chronic encephalopathy; the 'solvent team' project].
AB  - Long-term exposure to organic solvents can result in damage of the central
      nervous system. The WHO recognises the following stages: organic affective
      syndrome, mild chronic toxic encephalopathy (CTE), and severe CTE. There is no
      golden standard for the diagnosis of CTE. Mild CTE is characterised by fatigue,
      mood disturbances, memory and attention disorders. In the Netherlands, a so
      called 'solvent team' consisting of an occupational physician, a neurologist, a
      neuropsychologist and an occupational hygienist, assesses patients suspected of
      having CTE. The diagnostic procedure consists of three steps: (a) interview and
      blood tests, (b) the computer-based Neurobehavioral Evaluation System, and (c)
      assessment of an exposure index, neuropsychological investigation, and clinical
      neurological examination. In the period 1997-1999 approximately 250 patients were
      assessed yearly in the Netherlands; resulting in 50 diagnoses of mild CTE a year.
      The real incidence is most likely higher at present, but will decline due to
      diminished exposure to organic solvents.

PMID- 11236372
TI  - [Physical diagnosis--ascites].
AB  - The diagnosis of ascites can be made very likely by a good clinical history and a
      well-directed physical examination, if the patient suffers from a disease which
      can cause ascites. The physician should ask about recent weight gain, change in
      abdominal girth and ankle oedema. With a positive history, the likelihood of the
      presence of ascites may increase 3 to 4-fold. When the findings at physical
      examination are also positive, the likelihood may increase 10 to 20-fold. A fluid
      wave is the most specific but less sensitive symptom. Shifting dullness, bulging
      flanks and flank dullness are less specific but much more sensitive parameters.
      The presence of ascites is very unlikely if the prior probability is low and both
      the patient's answers and the findings at physical examination are negative.
      Abdominal ultrasound, the gold standard, is not strictly indicated for diagnosing
      ascites: if based on the trial tried: pretest probability, clinical history and
      physical examination, the diagnosis is very likely or very unlikely.
      Ultrasonography is always indicated, however, when ascites is suspected and a
      positive finding is of clinical relevance.

PMID- 11236373
TI  - [Diagnostic image (24). Ovary with a mature teratoma (so-called dermoid cyst)].
AB  - A 43-year-old woman had pain and a palpable swelling in the lower left abdomen.
      At laparotomy a mature teratoma of the ovary was removed.

PMID- 11236374
TI  - [From gene to disease; from CACNA1A to migraine].
AB  - Familial hemiplegic migraine (FHM) is a rare autosomal dominant subtype of
      migraine with aura. FHM is associated in half the families with mutations in the
      CACNA1A gene on chromosome 19P13, encoding the alpha-1A subunit of brain-specific
      P/Q-type calcium channels. P/Q-type calcium channels are important in
      neurotransmitter release. The first functional studies indicate that mutations
      causing FHM result in a gain or loss of function of P/Q-type calcium channels.
      Affected sib-pair analysis in families with migraine with and without aura
      indicates involvement of the CACNA1A gene in these more frequent types of
      migraine.

PMID- 11236375
TI  - [Risk of convulsions due to the use of bupropion as an aid for smoking
      cessation].
AB  - Bupropion is a new aid in smoking cessation. Since marketing of this product in
      the Netherlands (from December 1999 on), 7 cases of (possible) convulsions have
      been reported. In 3 cases there was a contraindication in the form of a history
      of epilepsy. The four other cases concerned tonic-clonic epileptic seizures in
      patients with no history of epilepsy and no combination with other medication. In
      view of the seriousness of this, already known, side effect of bupropion,
      physicians ought to be sensitive to situations with increased risk of this side
      effect. In addition it is advised to explain to the patient the proper use of
      bupropion, which is not comparable to nicotine chewing gum and should be
      swallowed whole due to the slow release properties of the tablet.

PMID- 11236376
TI  - [Bupropion; an effective new aid for smoking cessation].

PMID- 11236378
TI  - Behavioral healthcare tomorrow. Web-enabled challenges and solutions.

PMID- 11236377
TI  - AMIA 2000. Converging information, technology, and healthcare.

PMID- 11236379
TI  - Physician wanted--IT skills required.

PMID- 11236380
TI  - Cyberhealthcare: reshaping the physician-patient relationship.

PMID- 11236381
TI  - Transforming healthcare. The role of federal innovations.

PMID- 11236382
TI  - eHealthcareWorld 2000. Getting down to business.

PMID- 11236383
TI  - Computer telephony integration. Bringing together a host of new applications for
      healthcare.

PMID- 11236384
TI  - Currents in medical informatics. The Woods Hole experience.

PMID- 11236385
TI  - Ambulatory care. Implementing an integrated clinical and practice management
      system.

PMID- 11236386
TI  - Drugs, codes, standards, and other incompatible things in the dark.

PMID- 11236387
TI  - A clean slate: initiating a graduate program in health informatics.

PMID- 11236388
TI  - [Unexpected death by leukostasis and lung leukostatic tumors in acute myeloid
      leukemia. Study of four cases].
AB  - Four cases of unexpected death due to acute myeloid leukemia have been studied:
      myeloblastic M1 (case I and II), promyelocytic M3 (case III), myelomonocytic M4
      (case IV). Diagnosis was performed before death only in case III. Histological
      leukostasis was the most evident feature in all cases, particularly at the lung
      level, where tumor-like aspects were evident and widely diffused in case II. The
      last three cases were pregnant at the third trimester. Serious hemorrhagic
      complications were evident in all cases: CID in the former 3 cases and primary
      hyperfibrinolysis in the 4th, as demonstrated by the absence of intravascular
      cloths in many organs and especially in lung and kidney; abundant, on the
      contrary, in the former three cases. Leukostasis was not associated to hyper
      leucocytosis in all 4 cases, but associated to normal number of peripheral white
      cells (below normal level in case III). This phenomenon, that disagrees with
      literature data on acute or chronic reactivated myeloid leukemia leukostasis, may
      be due to the primary confination of the immature granuloblasts in the vascular
      bed, because of the hemoreologic effects connected with their deficient
      plasticity, that is essential for normal granulocytes to flow easily in the
      capillary bed. In all cases death was caused by breathing and cardiocirculatory
      insufficiency with the associated unceasing hemorrhages.

PMID- 11236389
TI  - [Beta-endorphin and stress hormones in patients affected by osteoarthritis
      undergoing thermal mud therapy].
AB  - BACKGROUND: Thermal mud is a therapeutic agent widely used in the treatment of
      painful arthritic processes. The mechanism by which mud therapy works is still
      not well known. Its effect continues for months after completion of treatment. In
      order to verify whether thermal mud treatment brings about changes in the
      production of hormone peptides from proopiomelanocortin, the levels of plasma
      beta-endorphin and some hormones of the pituitary-adrenal glands (ACTH and
      cortisol) were determined in patients affected by osteoarthritis undergoing
      thermal mud therapy. METHODS: The levels of plasma beta-endorphin and some
      hormones of the pituitary-adrenal glands (ACTH and cortisol) were assessed by
      radiometric methods in seventeen males affected by osteoarthritis. The patients
      underwent a cycle of twelve sessions of thermal mud therapy. The tests were
      carried out immediately before thermal treatment, immediately after the first
      session, twelve days after the start of treatment, and again one month after
      completion of the treatment. RESULTS: beta-endorphin levels decreased
      significantly twelve days after the start of treatment. The level was still
      lower, although not significantly, even thirty days after completion of the
      treatment. Plasma ACTH also decreased during treatment. The decrease of this
      hormone was progressive and persisted after completion of treatment. Significant
      variations compared to baseline were found only thirty days after completion of
      treatment. Plasma cortisol decreased significantly after only one session of mud
      therapy. This hormone did not decrease any further during treatment, however,
      after twelve days it was still significantly lower than baseline. After
      completion of treatment, cortisol slightly increased, but thirty days later it
      was still lower, although not significantly, than baseline. CONCLUSIONS: It may
      be suggested that thermal treatment, by reducing inflammation, reduced pain and
      therefore diminished the cause of stress.

PMID- 11236390
TI  - [Determination of carbohydrate trasferrin (CDT) in the legal medical assessment
      of being fit to drive].
AB  - BACKGROUND: According to the literature carbohydrate-deficient transferrin (CDT)
      is thought to be the most sensitive and specific marker of alcohol abuse, but
      must always be combined with other laboratory tests. Until now the amount of CDT
      that indicates a state of chronic alcoholism has not been established. Therefore,
      our aim was to quantify the percentage of CDT that discriminates social drinkers
      from alcoholics. METHODS: A retrospective study was carried out covering a period
      of four months on patients who came to us after having their driving licenses
      suspended for drink driving: 100 male and female subjects aged between 21 and 65
      years were examined. This population was compared to a control group of 50
      subjects matched for age, who consumed a moderate amount of alcohol, and had
      never had their driving licenses suspended. RESULTS: The percentage of CDT was
      found by heterogenous enzyme immunoassay that involves column separation and
      turbidimetry. There was a notable difference in the amount of CDT between the two
      groups. The ANOVA and Levene tests were used for statistical analysis.
      CONCLUSIONS: The authors found the percentage amount of CDT that discriminates
      the two groups, highlighting the important role of this marker of alcohol abuse
      in a relevant social context.

PMID- 11236392
TI  - Bioterrorism and public health.

PMID- 11236391
TI  - [Ethical issues of human experimentation with special reference to informed
      consent].
AB  - Human experimentation in order to develop new medical therapies creates very
      complex ethical problems: when is it possible to test a new therapy on a human
      subject? Is it always necessary his/her consent? Which information should be
      given to the subject before requesting his/her consent? How to behave in the case
      of minors, psychiatric patients and other subjects not perfectly free or able to
      understand the information provided? Is it right to subject a person to an
      experimentation from which he/she will not get any direct advantage? Which
      results can be published? In other words, which are the ethical limits of human
      experimentation? These are difficult questions, to which the authors tried to
      answer referring to some ethically significant human experimentations, such as
      those performed by Lind and Jenner in the XVIII century, and those carried out by
      the nazi doctors, from whose trial derived the Nuremberg Code, which introduced
      for the first time, at an international level, the principle of the informed
      consent. Some of the limits of this document, including the impossibility of
      doing research on subjects not able to give their informed consent, such as
      minors and psychiatric patients, were overcome by the Declaration of Helsinki,
      whose current version resulted from several subsequent revisions. According to
      this document, a major role is played by the Institutional Review Boards or
      Institutional Ethical Committees that have the heavy responsibility of evaluating
      the ethical connotations of human experimentations.

PMID- 11236393
TI  - Outbreak of trichinellosis associated with arctic walruses in northern Canada,
      1999.

PMID- 11236394
TI  - Is economic policy health policy?

PMID- 11236395
TI  - Dr Button and the airplane.

PMID- 11236396
TI  - The essential tension between absolute and relative causality.

PMID- 11236397
TI  - Cancer culture: epidemics, human behavior, and the dubious search for new risk
      factors.

PMID- 11236398
TI  - The search for cancer risk factors: when can we stop looking?
AB  - In recent decades, countless cohort, case-control, and ecologic studies have been
      conducted in the search for cancer risk factors. On the basis of knowledge gained
      from these studies, various influential commentaries have endeavored to classify
      the extent to which the total cancer burden is attributable to general categories
      of risk, such as diet, tobacco, sun exposure, and others. These commentaries have
      led to the conventional wisdom that most of the cancer burden is caused by
      environmental factors and relatively little is directly attributable to genetic
      susceptibility. In the face of the apparent knowledge that the cancer burden is
      essentially fully "explainable" on the basis of known environmental risks, this
      article addresses the conceptual and empirical basis of the continued search for
      new risk factors. It proposes that the extent of the aggregation of cancer within
      individuals in the population--that is, the occurrence of second primary cancers-
      is a crucial statistic in this context. A study of the incidence of second
      primary melanoma suggests that the bulk of the risk variation in this disease
      cannot be explained by known risk factors. The implications of these ideas for
      research strategy and for public health policy are discussed.

PMID- 11236399
TI  - The privatization of risk.
AB  - The privatization, or individualization, of risk factor knowledge has been
      largely responsible for a rising tide of criticism of epidemiology. The current
      debate seems polarized into 2 sides, those who support and those who attack "risk
      factor" epidemiology. This commentary aims to reinvigorate some of Geoffrey
      Rose's central arguments and show that this debate may miss a key point: a risk
      factor is a probabilistic concept that applies to an aggregate of individuals,
      not to a specific individual. Risk factor knowledge compels those in public
      health to seek actions that shift population distributions of these factors and,
      to do so, to understand their social, economic, and political determinants. The
      author links Rose's qualitative distinction between the causes of cases and the
      causes of incidence to an examination of the conceptual and quantitative limits
      of "individual risk" estimation. The attempt to predict individuals' futures on
      the basis of risk factor profile is especially prominent now with breast cancer.
      The author suggests reasons why a policy promoting private decision making about
      risk, while likely ineffective from a population standpoint, is viewed as the
      only feasible primary prevention option against this disease.

PMID- 11236400
TI  - The influence of geopolitical change on the well-being of a population: the
      Berlin Wall.
AB  - OBJECTIVES: Social cohesion is recognized as a fundamental condition for healthy
      populations, but social cohesion itself arises from political unity. The history
      of the Berlin Wall provides a unique opportunity to examine the effects of
      partition on social cohesion and, by inference, on health. METHODS: This
      ethnographic study consisted of examination of the territory formerly occupied by
      the Wall, formal and informal interviews with Berlin residents, and collection of
      cultural documents related to the Wall. Transcripts, field notes, and documents
      were examined by means of a keyword-in-context analysis. RESULTS: The separation
      of Berlin into 2 parts was a traumatic experience for the city's residents. After
      partition, East and West Germany had divergent social, cultural, and political
      experiences and gradually grew apart. CONCLUSIONS: The demolition of the Wall-
      the symbol and the instrument of partition--makes possible but does not ensure
      the reintegration of 2 populations that were separated for 40 years. The
      evolution of a new common culture might be accelerated by active attempts at
      cultural and social exchange.

PMID- 11236401
TI  - Can legislation prevent debauchery? Mother gin and public health in 18th-century
      England.
AB  - The "gin epidemic" of 1720 to 1751 in England was the first time that government
      intervened in a systematic fashion to regulate and control sales of alcohol. The
      epidemic therefore provides an opportunity to gauge the effects of multiple
      legislative interventions over time. Toward that end, we employed time series
      analysis in conjunction with qualitative methodologies to test the interplay of
      multiple independent variables, including real wages and taxes, on the
      consumption of distilled spirits from 1700 through 1771. The results showed that
      each of the 3 major gin acts was successful in the short term only, consistent
      with the state's limited resources for enforcement at the local level, and that
      in each instance consumption actually increased shortly thereafter. This was true
      even of the Gin Act of 1751, which, contrary to the assumptions of contemporaries
      and many historians, succeeded by accident rather than by design. The results
      also suggest that the epidemic followed the inverse U-shaped trajectory of more
      recent drug scares and that consumption declined only after the more deleterious
      effects of distilled spirits had been experienced by large numbers of people.

PMID- 11236402
TI  - State-level income inequality and individual mortality risk: a prospective,
      multilevel study.
AB  - OBJECTIVES: Previous studies have linked state-level income inequality to
      mortality rates. However, it has been questioned whether the relationship is
      independent of individual-level income. The present study tests whether state
      level income inequality is related to individual mortality risk, after adjustment
      for individual-level characteristics. METHODS: In this prospective, multilevel
      study design, the vital status of National Health Interview Survey (NHIS)
      respondents was ascertained by linkage to the National Death Index, with
      additional linkage of state-level data to individuals in the NHIS. The analysis
      included data for 546,888 persons, with 19,379 deaths over the 8-year follow-up
      period. The Gini coefficient was used as the measure of income inequality.
      RESULTS: Individuals living in high-income-inequality states were at increased
      risk of mortality (relative risk = 1.12; 95% confidence interval = 1.04, 1.19)
      compared with individuals living in low-income-inequality states. In stratified
      analyses, significant effects of state income inequality on mortality risk were
      found, primarily for near-poor Whites. CONCLUSIONS: State-level income inequality
      appears to exert a contextual effect on mortality risk, after income is adjusted
      for, providing further evidence that the distribution of income is important for
      health.

PMID- 11236403
TI  - All-cause and cause-specific mortality of immigrants and native born in the
      United States.
AB  - OBJECTIVES: This study examined whether US-born people and immigrants 25 years or
      older differ in their risks of all-cause and cause-specific mortality and whether
      these differentials, if they exist, vary according to age, sex, and
      race/ethnicity. METHODS: Using data from the National Longitudinal Mortality
      Study (1979-1989), we derived mortality risks of immigrants relative to those of
      US-born people by using a Cox regression model after adjusting for age,
      race/ethnicity, marital status, urban/rural residence, education, occupation, and
      family income. RESULTS: Immigrant men and women had, respectively, an 18% and 13%
      lower risk of overall mortality than their US-born counterparts. Reduced
      mortality risks were especially pronounced for younger and for Black and Hispanic
      immigrants. Immigrants showed significantly lower risks of mortality from
      cardiovascular diseases, lung and prostate cancer, chronic obstructive pulmonary
      diseases, cirrhosis, pneumonia and influenza, unintentional injuries, and suicide
      but higher risks of mortality from stomach and brain cancer and infectious
      diseases. CONCLUSIONS: Mortality patterns for immigrants and for US-born people
      vary considerably, with immigrants experiencing lower mortality from several
      major causes of death. Future research needs to examine the role of sociocultural
      and behavioral factors in explaining the mortality advantage of immigrants.

PMID- 11236404
TI  - Efficacy of a preventive intervention for youths living with HIV.
AB  - OBJECTIVES: HIV transmission behaviors and health practices of HIV-infected
      youths were examined over a period of 15 months after they received a preventive
      intervention. METHODS: HIV-infected youths aged 13 to 24 years (n = 310; 27%
      African American, 37% Latino) were assigned by small cohort to (1) a 2-module
      ("Stay Healthy" and "Act Safe") intervention totaling 23 sessions or (2) a
      control condition. Among those in the intervention condition, 73% attended at
      least 1 session. RESULTS: Subsequent to the "Stay Healthy" module, number of
      positive lifestyle changes and active coping styles increased more often among
      females who attended the intervention condition than among those in the control
      condition. Social support coping also increased significantly among males and
      females attending the intervention condition compared with those attending the
      control condition. Following the "Act Safe" module, youths who attended the
      intervention condition reported 82% fewer unprotected sexual acts, 45% fewer
      sexual partners, 50% fewer HIV-negative sexual partners, and 31% less substance
      use, on a weighted index, than those in the control condition. CONCLUSIONS:
      Prevention programs can effectively reduce risk acts among HIV-infected youths.
      Alternative formats need to be identified for delivering interventions (e.g.,
      telephone groups, individual sessions).

PMID- 11236405
TI  - Selective risk taking among needle exchange participants: implications for
      supplemental interventions.
AB  - OBJECTIVES: This study characterized social network context of HIV risk behavior
      among injection drug users who participated in a needle exchange program.
      METHODS: Interviews were conducted with 1184 injection drug users at the
      Baltimore Needle Exchange Program enrolled in an evaluation cohort. Analysis
      consisted of multiple logistic regression with statistical adjustment for the
      interdependence of observations. RESULTS: Of the 203 (17.1%) injection drug users
      who reported using a syringe after someone else, 78.3% reported sharing with
      close friends, and the adjusted odds ratio of any sharing and sharing with close
      friends was 30.9. Injection drug users were more likely to report sharing with a
      strong-tie close friend (adjusted odds ratio = 1.52) and less likely to report
      sharing with other close friends if those friends were weak ties and new to their
      network. Friendship ties were not stable, with fewer than 30% of the friends
      being repeat nominations. CONCLUSIONS: These data show that many injection drug
      users engage in selective risk taking that may minimize their disease risk
      exposure in the short term. The turnover in networks, however, suggests that
      programs need to emphasize the importance of exclusive use.

PMID- 11236406
TI  - Evaluating OSHA's ethylene oxide standard: exposure determinants in Massachusetts
      hospitals.
AB  - OBJECTIVES: This study sought to identify determinants of workplace exposures to
      ethylene oxide to assess the effect of the Occupational Safety and Health
      Administration's (OSHA's) 1984 ethylene oxide standard. METHODS: An in-depth
      survey of all hospitals in Massachusetts that used ethylene oxide from 1990
      through 1992 (96% participation, N = 90) was conducted. Three types of exposure
      events were modeled with logistic regression: exceeding the 8-hour action level,
      exceeding the 15-minute excursion limit, and worker exposures during unmeasured
      accidental releases. Covariates were drawn from data representing an ecologic
      framework including direct and indirect potential exposure determinants. RESULTS:
      After adjustment for frequencies of ethylene oxide use and exposure monitoring, a
      significant inverse relation was observed between exceeding the action level and
      the use of combined sterilizer-aerators, an engineering control technology
      developed after the passage of the OSHA standard. Conversely, the use of positive
      pressure sterilizers that employ ethylene oxide gas mixtures was strongly related
      to both exceeding the excursion limit and the occurrence of accidental releases.
      CONCLUSIONS: These findings provide evidence of a positive effect of OSHA's
      ethylene oxide standard and specific targets for future prevention and control
      efforts.

PMID- 11236407
TI  - A comparison of knowledge and attitudes about diet and health among 35- to 75
      year-old adults in the United States and Geneva, Switzerland.
AB  - OBJECTIVES: This study compared responses of US and Geneva residents to items on
      analogous questionnaires concerning knowledge and attitudes about diet and
      health. METHODS: Comparable data were available from 2 population-based sample
      surveys: the Cancer Control Supplement of the 1987 National Health Interview
      Survey and the 1994 Bus Sante 2000 in Geneva, Switzerland. Samples included
      10,366 US respondents and 698 Geneva respondents, aged 35 to 74 years. The
      analysis involved descriptive statistics, contingency tables, and linear
      regression models. RESULTS: In both the United States and Geneva, health
      consciousness was greater among women and more highly educated persons than among
      other groups. Compared with Americans, Genevans assigned more importance to
      avoiding salt, sugar, and overweight (odds ratio = 1.6, 2.9, and 5.9,
      respectively) and less importance to lowering cholesterol (odds ratio = 0.6).
      Genevans were more likely to recognize the relatively high fiber content of
      lettuce, carrots, and apples. Recognition of low-fat foods was slightly better in
      the United States. CONCLUSIONS: Knowledge and attitudes differed despite high
      general diet and health awareness in both populations. Identifying why generally
      similar dietary guidance messages are embraced to different extents across
      cultures may facilitate global implementation.

PMID- 11236408
TI  - Trends in infectious disease hospitalizations among American Indians and Alaska
      Natives.
AB  - OBJECTIVES: This study sought to describe trends in hospitalizations associated
      with infectious diseases among American Indians and Alaska Natives. METHODS:
      Infectious disease hospitalizations and rates among American Indians and Alaska
      Natives from 1980 through 1994 were examined via Indian Health Service hospital
      discharge data and compared with published trends for the general US population.
      RESULTS: Annual hospitalization rates for infectious diseases among American
      Indians and Alaska Natives decreased by 31.0% between 1980 and 1994. Infectious
      disease hospitalizations accounted for 16.3% of all hospitalizations in 1980 and
      21.2% in 1994, an increase of 30.1%. In 1994, the age-adjusted infectious disease
      hospitalization rate for American Indians and Alaska Natives was 1863 per 100,000
      population, approximately 21% greater than that for the general US population.
      CONCLUSIONS: Hospitalization trends for infectious diseases show that there has
      been improvement in the health status of American Indians and Alaska Natives but
      also indicate that this population has a higher infectious disease burden than
      the general US population.

PMID- 11236409
TI  - Sudden infant death syndrome, maternal smoking during pregnancy, and the cost
      effectiveness of smoking cessation intervention.
AB  - OBJECTIVES: This study analyzed the relationship between prenatal maternal
      smoking and sudden infant death syndrome (SIDS) and examined the cost
      effectiveness of smoking cessation interventions. METHODS: All recorded US
      singleton SIDS deaths from the 1995 birth cohort with birthweight exceeding 500 g
      were investigated. Infants with available maternal smoking data were matched with
      controls who survived to 1 year. Conditional logistic regression was used to
      estimate SIDS risks and accompanying cost-effectiveness. RESULTS: A total of
      23.6% of singleton SIDS deaths appear to be attributable to prenatal maternal
      smoking. Typical cessation services available to all pregnant smokers could avert
      108 SIDS deaths annually, at an estimated cost of $210,500 per life saved.
      CONCLUSIONS: Typical prenatal smoking cessation programs are highly cost
      effective but have limited impact on the population incidence of SIDS.

PMID- 11236410
TI  - Pregnancy complications and outcomes among overweight and obese nulliparous
      women.
AB  - OBJECTIVES: This study examined the associations between prepregnancy weight and
      the risk of pregnancy complications and adverse outcomes among nulliparous women.
      METHODS: We conducted a population-based cohort study with 96,801 Washington
      State birth certificates from 1992 to 1996. Women were categorized by body mass
      index. Multivariate logistic regression was performed. RESULTS: The rate of
      occurrence of most of the outcomes increased with increasing body mass index
      category. Compared with lean women, both overweight and obese women had a
      significantly increased risk for gestational diabetes, preeclampsia, eclampsia,
      cesarean delivery, and delivery of a macrosomic infant. CONCLUSIONS: Among
      nulliparous women, not only prepregnancy obesity but also overweight increases
      the risk of pregnancy complications and adverse pregnancy outcomes.

PMID- 11236411
TI  - Prevalence and predictors of physical partner abuse among Mexican American women.
AB  - OBJECTIVES: This study determined the lifetime prevalence of physical abuse by a
      current partner among women of Mexican origin and assessed factors associated
      with abuse. METHODS: Data are for a subsample of 1155 women with current partners
      from a larger population-based cross-sectional survey of US residents of Mexican
      origin. RESULTS: The self-reported prevalence of physical abuse by a current
      partner was 10.7%. In multivariate analysis, factors associated with physical
      abuse included US birthplace (odds ratio = 2.1; 95% confidence interval = 1.24,
      3.56), young age, urban residence, and having 4 or more children. Social support
      and regular church attendance were protective. CONCLUSIONS: The self-reported
      prevalence of physical abuse among Mexican American women is high. US birth is
      associated with increased risk of abuse. Community-based prevention efforts
      should be aimed at this population.

PMID- 11236413
TI  - The impact of referral to a primary physician on cervical cancer screening.
AB  - OBJECTIVES: The purpose of this study was to determine whether referral to a
      primary physician led to an increase in screening for cervical cancer among women
      enrolled in Delaware Medicaid. METHODS: Medicaid claims data were used to compare
      annual Papanicolaou (Pap) test rates for women referred to a primary care
      physician or obstetrician (n = 365) with rates for age-matched comparison women
      who were not referred (n = 1799). RESULTS: Thirty-eight percent of referred women
      and 27% of comparison women underwent Pap tests (adjusted odds ratio = 1.71; 95%
      confidence interval = 1.33, 2.20). CONCLUSIONS: Referral to a primary physician
      had a positive impact on cervical cancer screening among the study participants.

PMID- 11236412
TI  - Dieting and smoking initiation in early adolescent girls and boys: a prospective
      study.
AB  - OBJECTIVES: This analysis tested the relation between dieting frequency and risk
      of smoking initiation in a longitudinal sample of adolescents. METHODS: From 1995
      to 1997, 1295 middle school girls and boys participated in a nutrition and
      physical activity intervention study. The prospective association between dieting
      frequency at baseline and smoking initiation 2 years later was tested. RESULTS:
      Compared with girls who reported no dieting at baseline, girls who dieted up to
      once per week had 2 times the adjusted odds of becoming smokers (odds ratio =
      2.0; 95% confidence interval = 1.1, 3.5), and girls who dieted more often had 4
      times the adjusted odds of becoming smokers (odds ratio = 3.9; 95% confidence
      interval = 1.5, 10.4). CONCLUSIONS: Dieting among girls may exacerbate risk of
      initiating smoking, with increasing risk with greater dieting frequency.

PMID- 11236414
TI  - Trends in cardiovascular disease risk factor prevalence among male transport
      workers: Bulgaria, 1986 to 1997.
AB  - OBJECTIVES: This study investigated cardiovascular risk factors among male
      transport workers in Bulgaria. METHODS: Comparisons were made of data from
      independent surveys conducted among male transport workers aged 30 to 59 years in
      Sofia, Bulgaria, during 1986 (n = 1146) and 1996-1997 (n = 638). RESULTS: Smoking
      prevalence increased from 49% to 59% between 1986 and 1996-1997. Among current
      smokers, the percentage smoking 15 or more cigarettes per day decreased. The
      prevalence of elevated body mass index, hypertension, or angina pectoris did not
      change. CONCLUSIONS: Smoking prevalence rates increased during the study period;
      the prevalence of other risk factors remained high.

PMID- 11236415
TI  - Medicaid managed care in New York City: recent performance and coming challenges.
AB  - OBJECTIVES: This study evaluated New York City's voluntary Medicaid managed care
      program in terms of health care use and access. METHODS: A survey of adults in
      Medicaid managed care and fee-for-service programs during 1996-1997 was analyzed.
      RESULTS: Responses showed significant favorable risk selection into managed care
      but little difference in use of health care services. Although some measures of
      access favored managed care, many others showed no difference between the study
      groups. CONCLUSIONS: The early impact of mandatory enrollment will probably
      include an increase in the average risk of managed care enrollees with little
      change in beneficiary use and access to care.

PMID- 11236417
TI  - Public health is already a profession.

PMID- 11236416
TI  - Emergency department screening for asymptomatic sexually transmitted infections.
AB  - OBJECTIVES: This study assessed the prevalence and correlates of asymptomatic
      genital tract infection with Neisseria gonorrhoeae and Chlamydia trachomatis
      among emergency department patients. METHODS: Individuals seeking emergency
      department evaluation for nongenitourinary complaints provided urine samples for
      N gonorrhoeae and C trachomatis testing by ligase chain reaction and completed a
      sociodemographic and behavioral questionnaire. RESULTS: Asymptomatic N
      gonorrhoeae or C trachomatis was found in 9.7% of persons tested. Correlates of C
      trachomatis infection included younger age, residence in high-morbidity zip code
      areas, previous history of N gonorrhoeae or C trachomatis, and number of sex
      partners in the past year. CONCLUSIONS: Urine-based screening of asymptomatic
      emergency department patients detected significant numbers of N gonorrhoeae and C
      trachomatis infections. Targeted screening programs may contribute to community
      level prevention and control of sexually transmitted infections.

PMID- 11236418
TI  - Professionalizing public health.

PMID- 11236419
TI  - "Regularizing" public health practitioners.

PMID- 11236420
TI  - It's time we became more political as a profession.

PMID- 11236421
TI  - Educating the public health workforce.

PMID- 11236422
TI  - Political competencies and public health leadership.

PMID- 11236423
TI  - Prevention of toddler drowning in pools: isolation vs perimeter fencing.

PMID- 11236424
TI  - Expanded family and medical leave.

PMID- 11236425
TI  - Reducing the incidence of blindness, lower extremity amputation, and oral health
      complications in minority populations due to diabetes.

PMID- 11236426
TI  - Preserving consumer choice in an era of religious/secular health industry mergers
      (position paper).

PMID- 11236427
TI  - Supporting access to midwifery services in the United States (position paper).

PMID- 11236428
TI  - Effective interventions for reducing racial and ethnic disparities in health.

PMID- 11236429
TI  - Making medicines affordable: the price factor (position paper).

PMID- 11236430
TI  - Support for a new campaign for universal health care.

PMID- 11236431
TI  - Affirming the importance of regulating pesticide exposures to protect public
      health.

PMID- 11236432
TI  - Support for international action to eliminate persistent organic pollutants.

PMID- 11236434
TI  - The precautionary principle and children's health.

PMID- 11236433
TI  - Creating healthier school facilities.

PMID- 11236435
TI  - Reducing the rising rates of asthma.

PMID- 11236436
TI  - Maximizing public health protection with integrated vector control.

PMID- 11236437
TI  - Protecting OSHA's jurisdiction over home workplaces.

PMID- 11236439
TI  - Effective public health assessment, prevention, response, and training for
      emerging and re-emerging infectious diseases, including bioterrorism.

PMID- 11236438
TI  - Drinking water quality and public health (position paper).

PMID- 11236440
TI  - Confirming need for protective national health-based air quality standards.

PMID- 11236441
TI  - Public health impacts of job stress.

PMID- 11236442
TI  - Public health role of the National Fire Protection Association in setting codes
      and standards for the built environment.

PMID- 11236443
TI  - Raising income to protect health.

PMID- 11236444
TI  - International trade policy and issues of improving access to drugs for HIV/AIDS
      and other life-threatening and disabling diseases.

PMID- 11236445
TI  - Joint resolution in support of National Public Health Performance Standards
      Program.

PMID- 11236446
TI  - The need for continued and strengthened support for immunization programs.

PMID- 11236447
TI  - Eliminating access barriers in public health meetings.

PMID- 11236448
TI  - International multilateral and bilateral debt relief.

PMID- 11236449
TI  - Encourage healthy behavior by adolescents.

PMID- 11236450
TI  - Ensuring optimal vision performance in visually at risk drivers.

PMID- 11236451
TI  - The need for mental health and substance abuse services for the incarcerated
      mentally ill.

PMID- 11236453
TI  - Criteria for assessing the quality of health information on the Internet.

PMID- 11236452
TI  - Preventing genocide.

PMID- 11236454
TI  - Discontinuation of the use of the island-municipality of Vieques, P.R., for the
      US Navy's training exercises.

PMID- 11236455
TI  - Research and intervention on racism as a fundamental cause of ethnic disparities
      in health.

PMID- 11236456
TI  - Opposition to the CRACK campaign.

PMID- 11236457
TI  - Restoration of nutrition and health benefits eligibility to documented
      immigrants.

PMID- 11236458
TI  - Resolution to improve the social conditions that contribute to health.

PMID- 11236459
TI  - Addressing the use of fluoroquinolone antibiotics in agriculture.

PMID- 11236460
TI  - Establishment of a Medicare prescription drug benefit.

PMID- 11236462
TI  - Trust fund for developing countries to meet national commitment under the WHO
      Framework Convention for Tabacco Control.

PMID- 11236461
TI  - Support the framework for action on oral health in America: a report of the
      Surgeon General.

PMID- 11236463
TI  - Participation of health professionals in capital punishment.

PMID- 11236464
TI  - Condemnation of pharmaceutical manufacturers' retaliatory tactics.

PMID- 11236465
TI  - [The concept of "ecopolis": an ecological and hygienic approach to planning and
      creating populated localities].

PMID- 11236466
TI  - [The necessity of including Cryptosporidium oocysts among indicators of epidemic
      safety of drinking water].
AB  - The paper provides evidence that Cryptosporidium oocysts should be included as an
      indicator of the epidemic safety of drinking water in Russia. This is evidenced
      by the fact that there a wide spread of cryptosporidiosis in animals and man, of
      its causative agent in the environment; large global outbursts of the infection;
      no sanitary and parasitological drinking water monitoring in of the country, the
      use of the parasitological indicator to assess the drinking water in some
      countries (USA, UK, Ukraine, etc.).

PMID- 11236467
TI  - [The informative value of biochemical and cytochemical markers in laboratory
      animals during field tests].
AB  - Field tests (delivery of animals to differently polluted areas having) were
      carried out. The criterial significance of biochemical and cytochemical tests of
      bronchoalveolar lavage (BAL) from the animals was defined. The biochemical tests
      revealed significant changes in total protein, cholesterol, phospholipids,
      phospholipase A, histamine, serotonin, and others, which indicates metabolic
      dysfunction in BAL. The findings suggest that the lysosomal cell membranes are
      disorganized and the permeability of cell mitochondrial membranes is impaired.
      Thus, analyzing the findings makes it possible to identify the key links of
      damages and to define the true significance of environmental factors in realizing
      the mechanisms of pulmonary preabnormality.

PMID- 11236468
TI  - [Toxicological and sanitary evaluation of air pollution by substances discharged
      during managing of urban dumping soil].
AB  - The paper presents the results of sanitary and hygienic investigations whose
      reason was the situation established with the removal of dumping earth in the
      dwelling area of Mitino Microdistrict 8 gamma. The removed dumping earth found to
      have formaldehyde, benzenes, acetaldehyde, phenols, aromatic hydro carbons,
      polyaromatic compounds was a source of bad smelling substances that had entered
      the ambient air. A special study of the earth showed that it might yield volatile
      and bad smelling compounds, such as organic sulfides, aldehydes, mercaptans,
      ketones, etc. Their harmful health effects (during operations and in the late
      period) seem to be unlikely. When such work is under way, it is necessary to
      inform the population about possible consequences.

PMID- 11236469
TI  - [Results of radiation monitoring in Moscow].
AB  - The results of assessing the radiation situation due to global fallouts, obtained
      from measurement of 137Cs and 90Sr in over 400 samples from natural environmental
      objects in Moscow in 1979-1999 have indicated that the levels of the substances
      in the atmospheric fallouts are in agreement with the mean Russian levels and the
      mean annual activity of these radionuclides in the ambient air are 6 orders lower
      than the allowable values laid down in NRB-99. In Moscow, the mean effective dose
      of external exposure to natural and cosmogenic radionuclides is no greater than 1
      m3v a year. The individual effective doses of internal and external exposures of
      the population to global fallouts averages 13 mu k3v a year.

PMID- 11236470
TI  - [Prospects of development of social-sanitary monitoring as a basic mechanism of
      providing the population's wellbeing and the role of the journal "Gigiena i
      Sanitariia " in covering the topical problems].

PMID- 11236471
TI  - [Radio-ecological and hygienic assessment of consequences of forest fires in the
      areas polluted during the Chernobyl accident].
AB  - Retransfer of radionuclides on the condensation trails of Chernobyl radioactive
      fallouts during forest fires has been experimentally evaluated and their
      mathematical transfer model verified. It has been shown that radionuclide
      retransfer will make no great impact on additional pollution of an area even
      under the most unfavourable conditions. The contribution of convective and non
      convective components of transfer to the formation of a radioactive aerosol
      concentration field has been assessed. Time course of changes in the
      concentration of radioactive aerosol and its dispersive composition are shown in
      different phases of fire and at different distance from its source.

PMID- 11236472
TI  - [Present-time problems of medical waste].
AB  - To handle medical garbage is a urgent problem in Russia, which has been poorly
      solved so far. This kind of garbage is epidemiologically hazardous and may
      contain radioactive substances. The published sanitary rules have approved five
      hazard classes for medical garbage. Little attention is paid to technologies of
      their elimination.

PMID- 11236473
TI  - [Main factors of occupational risk for railway workers].
AB  - The paper shows the specific features of development of occupational diseases
      associated with the classes of working conditions by the degree of hazard and
      risk. It provides a scientifically founded evidence for that the indicators of a
      potential risk of working conditions should be included into the methodology of
      assessment of a professional risk.

PMID- 11236475
TI  - [Sanitary classification of publishing products].
AB  - The natural asthenopic pattern of the process of reading shows it necessary to
      set sanitary standards of publishing production, namely, printing type styling
      and the printing quality of publications. The necessity of sanitary
      classification of publishing production stems from the specificity of reading the
      publications of different functional uses and from the physiological features of
      vision in different age group readers. The developed sanitary classification of
      printing production is based on the researches into the actual visual load while
      reading the publications of different types by readers of different ages.

PMID- 11236474
TI  - [Working conditions and morbidity of workers at the present-day shoe
      manufacturing factory].
AB  - Poor working factors of present-day industry (SALAMANDER technology) include high
      intensity of labour, monotonicity, forced posture, constant wide-range noise,
      fumes of organic solvents, dust of organic origin, etc. The working conditions in
      producing departments are considered to be of degrees of 1-3 of hazard class 3.
      The highest incidence rates were noted in age groups under 30 years and above 50
      years and in workers with over 10-year length of service. There were prevalent
      acute respiratory diseases, influenza, osteomuscular and connective tissue,
      hypertensive and ENT diseases in the pattern of mortality with temporary
      disability. Comprehensive medical examinations revealed high incidence of ENT
      diseases due to exposure to chemical agents and organic dust.

PMID- 11236476
TI  - [A study of the intake of zinc, copper and selenium by Moscow preschool
      children].
AB  - The paper presents the results of comprehensive study of the provision of Moscow
      preschool age children with zinc, copper, and selenium, which involved assessment
      of their dietary intake of these substances, analysis of the provision with these
      trace elements by using non-invasive biochemical studies, and examination of the
      children's physical development and morbidity. Comparison of the data on the
      levels of zinc, copper, and selenium in the hair, nail, and saliva with scanty
      data available in the literature leads to the conclusion that Moscow preschool
      children show subnormal provision with these trace elements, which is not
      accompanied by clinical symptoms of their deficiency.

PMID- 11236477
TI  - [Providing athletes with trace elements during intensive exercise].
AB  - On the day of 30-km cross-country running, the content of iron, copper, and
      manganese in the diets of highly skilled adult athletes was found to be in the
      lower normal physiological range for those who do not go in for sports. During
      intensive exercise the intestinal and renal excretion of these substances was
      much greater than their dietary intake. The balance of all three substances was
      negative. Losses of iron and copper were not compensated for in the presence of
      their inadequate intake in the subsequent 3 days of rest following the race. The
      enrichment of diets with a complex of iron, copper, and manganese resulted in
      their retention in the athletes. As medical iron intake increased, there was a
      significant rise in the excretion of copper and manganese through the
      gastrointestinal tract.

PMID- 11236478
TI  - [Characteristics of goiter endemic in Kuzbass].
AB  - The purpose of the present study was to comprehensively assess goiter endemia in
      Kuzbass. The spread of goiter was examined in its population. The severity and
      intensity of goiter endemia were assessed. Its causes and risk factors were
      revealed. The Kemerovo region was found to be an area of moderate goiter endemia
      with a tendency for its severity. The wide spread of iodine deficiency in the
      population, which is associated with low dietary iodine intake, is a cause of
      goiter endemia in Kuzbass.

PMID- 11236479
TI  - [Principal approaches to standardization of biological contaminants].

PMID- 11236480
TI  - [Sanitary assessment of iodine levels in the environment and their impact on
      children's health].
AB  - The Irkutsk province and the Republic of Buryatia which are a part of the Baikal
      Region (Siberia) were studied for environmental iodine balance. The water and
      local foodstuffs were found to show low iodine levels (they being 0.2 to 6.9
      micrograms/l). In children, iodine deficiency was detected in 60-87% of the total
      number examined. There was a relationship between of the severity of neurological
      symptoms, the onset of thyroid diseases, general morbidity, physical development,
      iodine levels in the body. It is concluded that iodine deficiency has a great
      impact on the development of the regional pathology in children.

PMID- 11236481
TI  - [Substantiation of optimal education-training load for preschool children 3-4
      years of age].
AB  - The study was undertaken to make a sanitary regulation of educational and
      training load in junior and middle group preschool children of general children's
      educational institutions (CEIs). Experts' assessment was chosen to study the
      impact of regular educational and training load on the child's functional status.
      The experts were tutors and methodologists of CEIs (n = 186). The study has
      revealed the optimum number of lessons a day and a week, their duration and ratio
      in the weekly curriculum of lessons that are different in nature and showed it
      necessary to determine a vacation in the middle of a school year and to reduce
      the number of children in a group.

PMID- 11236482
TI  - [Health of children residing in an atomic plant area].

PMID- 11236483
TI  - [Criteria of early diagnosis of borderline nervous-mental disorders in young
      school children].
AB  - The total technogenic load and ecological situation of two Kazan districts were
      determined. A complex of unfavorable environmental factors has an adverse impact
      of the mental and emotional status of children who had similar social, sanitary,
      and history data, which makes itself evident in the fact that the girls showed
      worse intellectual and mnestic activities and the boys had increased anxiety. It
      is concluded that it is expedient to use tests for estimating the children's
      mental and emotional status for making a predisease diagnosis of environmentally
      induced conditions in the follow-up post of a local social and sanitary
      monitoring network.

PMID- 11236485
TI  - [Mapping as a method of detecting increased cancer risk areas in industrial
      cities].

PMID- 11236484
TI  - [Impact of chemical pollution of the Great Lakes on fish consumers (review)].

PMID- 11236486
TI  - [Determination of heterocyclic inhibitors of nitrification in environmental
      objects and biomaterials].

PMID- 11236487
TI  - [Methods of determining chloramphenicol in the workplace air].

PMID- 11236488
TI  - [Resolution of the Plenary Session of the All-Russian Scientific Medical Society
      of Hygienists and Sanitarians on software and urgent measures of further
      development of social-sanitary monitoring systems].

PMID- 11236489
TI  - [Ecological-sanitary problems of the preservation of the population's health
      (according to the proceedings of the scientific-practical conference)].

PMID- 11236490
TI  - [Theory and practice of the evaluation of combined effects of chemical
      environmental air pollution].

PMID- 11236491
TI  - [Effect of microalgae on viability of microorganisms in the natural and
      artificial environment].
AB  - The data of literature on complicated relationships between microorganisms and
      microalgae in algobacterial associations with microalgae often playing the
      leading role are analyzed. Under these conditions inhibiting and stimulating
      substances synthesized by microalgae, as well as their nutritional value, may
      have an essential impact on the state of the bacterial population. Apparently
      that microalgae may become the main substrate in the development of new culture
      media (ecologically pure culture media, media for the reversion of the
      noncultured forms of bacteria into the vegetative state, media for the prolonged
      preservation of microbes in the noncultured form).

PMID- 11236492
TI  - [Clinico-epidemiological characteristics of a minor outbreak of typhoid fever in
      the Smolensk region in 1998].

PMID- 11236493
TI  - [Seroimmunologic monitoring of microorganisms of Rickettsia and Bartonella
      species microorganisms in the Moscow region].
AB  - Serological study of 788 blood sera, taken from residents of the Moscow region
      was conducted using antigens of microorganisms of the genera Rickettsia and
      Bartonella. The first group under examination consisted of 355 patients with
      diagnosed diseases of nonreckettsial nature. The second group includes 433
      healthy adults working at a meat processing and packing factory. The main method
      used for sera survey was the indirect immunofluorescence test. In the sera taken
      from the first group of subjects specific antibodies to R. prowazekii, R. typhi,
      B. quintana, B. henselae antigens were detected in 2.3%, 5.1%, 4.0% and 2.9% of
      serum samples respectively. In the serum samples taken from the second group the
      proportion of antibodies to R. prowazekii, R. typhi, B. quintana, B. henselae
      antigens was different: 0.5%, 3.3%, 1.7% and 4.0% respectively. In total,
      specific antibodies to R. typhi and B. henselae prevailed over specific
      antibodies to R. prowazekii and B. quintana twofold.

PMID- 11236494
TI  - [A large-scale epidemic of diphtheria in Moscow in recent years: patterns of
      development].
AB  - Data on the dynamics of diphtheria morbidity in Moscow in 1958-1999 are
      presented. The last epidemic which started at the end of the 1980s and reached
      its peak in 1994, giving a 59-fold rise in morbidity in comparison with the pre
      epidemic period, is characterized in detail. During the epidemic 12,267 persons
      fell ill, 454 of them died (mortality rate was 4%). Having started in Moscow, the
      epidemic gradually spread not only over the territory of Russia, but also over
      some other republics of the former Soviet Union (Ukraine, Belarus, etc.).
      Possible causes of this epidemic emergency are considered. The ever increasing
      share of adult population among persons affected by the epidemic (75%) is noted.
      The infection adults is characterized by severity of clinical manifestations and
      increased morbidity among adults, is shown. Under complicated social and economic
      conditions (crisis situation) the increase of groups of high risk which included
      unemployed adults of working age, retirees as well as socially non-adapted
      persons, was registered. Mainly these groups determined tense epidemiological
      situation in diphtheria in Moscow.

PMID- 11236495
TI  - [Water-borne outbreak of serous meningitis caused by Echovirus-30 in Belarus].
AB  - In recent years outbreak of enterovirus infections caused by Echovirus-30 were
      rather frequently registered in different European countries. A major outbreak
      caused by this virus took place during the summer-autumn period of 1997 in the
      city of Gomel, Belarus. Sanitary epidemiological and molecular epidemiological
      studies made it possible to determine that the outbreak was water-borne. The
      sequence analysis of Echovirus-30 strains isolated from water and the
      cerebrospinal fluid of patients revealed a minor divergence between them (0.2%)
      indicative of their practical identity. The comparison of the Belorussian
      isolates with the strains isolated in Europe in 1994-1998 also showed a small
      percentage of differences in their genomes, which showed that the outbreak of
      Echovirus-30 infection was probably brought to Belarus from the territories of
      European countries.

PMID- 11236496
TI  - [Measles: prospects of vaccine prophylaxis and decrease of morbidity in Moscow].
AB  - The results of the prolonged epidemiological surveillance on measles in Moscow
      are presented. The detailed analysis of the influence of immunization on the
      level of measles morbidity has been made. Changes in the age structure of measles
      patients with an essential increase in the proportion of adolescents and adults
      due to mass vaccination of the child population are shown. High risk groups have
      been determined according to the data of serological screening and
      epidemiological surveillance. The prospects of the vaccinal prophylaxis of
      measles under present conditions, as the basic intervention for achieving
      sporadic level of morbidity in this infection and further eradication are
      evaluated.

PMID- 11236497
TI  - [Immunotropic and immunogenic properties of Burkholderia pseudomallei surface and
      membrane antigens].
AB  - The immunotropic and immunogenic properties of some chromatographic fractions of
      B. pseudomallei surface antigenic complex, as well as the preparations of B.
      pseudomallei outer and cytoplasmic membranes, were studied. The difference
      between the biopolymers under study in cytotoxicity, humoral and cell-mediated
      immunity characteristics, phagocytic activity were established. Some antigenic
      fractions (B, C, C1, H) showed perceptible protective activity (25-60%) in
      experiments on mice infected with B. pseudomallei virulent strain. One of the
      preparations of cytoplasmic membrane (CM-1) was also found to have protective
      properties (30%). Complex immunization with the antigenic complexes under study,
      introduced in combination with the immunomodulating agent Bromantan, was shown to
      enhance the protective effect.

PMID- 11236498
TI  - [Cultivation of Leptospira in a liquid culture medium with lysed rabbit blood].
AB  - A new method of the preparation of liquid culture medium for the cultivation of
      Leptospira has been developed on the basis of multiple freezing and thawing of
      defibrinated rabbit blood. A higher productivity of the new medium in comparison
      with the medium used in common practice has been established. The medium having a
      new composition is suitable for cultivation of Leptospira and the accumulation of
      biomass. The advantage of the medium made is in addition to high growth
      properties, the its economic efficiency and availability for practical
      laboratories.

PMID- 11236499
TI  - [Immunotherapy in the complex treatment of patients with atopic dermatitis with
      sensitization to house dust mites].
AB  - Ninety-nine patients aged 16-52 years with disseminated atopic dermatitis at the
      remission were examined and treated. The patients were divided into 3 groups
      according to the method of therapy. Group 1 (28 patients aged 17-52 years, found
      to be sensitive to Dermatophagoides pteronyssinus and D. farinae) received, in
      addition to standard treatment, immunotherapy (oral hyposensitization with mite
      allergens) in combination with ointment containing retinopalmitate and
      methyluracil. Group 2 (39 patients aged 17-40 years) received standard treatment
      combined with the administration of placebo. Group 3 (32 patients aged 16-27
      years) received only standard therapy. Groups 2 and 3 were used for comparison.
      The results of treatment were evaluated according to changes in the immune status
      of the patients and a complex of clinical characteristics. Essential improvement
      in clinical characteristics and the normalization of immunological parameters
      were registered in group 1, which proved that immunotherapy was effective and
      safe.

PMID- 11236500
TI  - [Status of local reproductive tract immunity in men with inflammatory diseases of
      the reproductive system].
AB  - The clinico-immunological study of 80 patients with chronic prostatitis of
      different etiology was carried out. As controls, 20 healthy adult males were
      used. Mucous membranes of the reproductive tract were found to have different
      mechanisms of antimicrobial protection whose disturbances led to the inflammatory
      process. The clinico-immunological analysis carried out in the course of this
      study made it possible to state that, in contrast to healthy adults, pronounced
      changes in the characteristics of the local immunity status of the reproductive
      system occur in chronic prostatitis patients.

PMID- 11236501
TI  - [Dependence of immunosuppressive action of lipopolysaccharide on degree of
      Salmonella pathogenicity].
AB  - Immunosuppressive activity of Salmonella typhimurium extracellular
      lipopolysaccharide (LPS) was studied. In this study isogenic S. typhimurium
      strains with different degree of virulence were used. The attenuation of these
      strains was linked with mutations on their chromosome (altered synthesis of RNA
      polymerase or gyrase DNA) or their own virulence plasmid (the insertion of
      transposon Tn-5). To obtain LPS fraction with different molecular weights, the
      filtrate of bacterial culture was subjected to gel filtration through a column
      packed with Sephadex G-200. The immunosuppressive action of LPS fractions was
      determined on the model of delayed-type hypersensitivity to nonbacterial antigen
      in experiments on BALB/c mice. The study revealed that transposon-mediated
      mutation on plasmid, accompanied by the attenuation of salmonellae, led to the
      loss of immunosuppressive activity of the high-molecular heat-sensitive component
      of LPS; only the second heat-resistant component with medium molecular weight
      retained its activity. The presence of two chromosomal attenuating mutations
      (rifr nalr) was accompanied by the loss of immunosuppressive activity in both
      components of LPS.

PMID- 11236502
TI  - [Functional and metabolic activity of peripheral blood neutrophils in acute viral
      hepatitis B and C].
AB  - The functional metabolic activity of peripheral blood neutrophils in acute virus
      hepatitis B (VHB) and/or virus hepatitis C (VHC) was evaluated. 48 patients were
      examined; of these, VHB was diagnosed in 28 patients and VHC was diagnosed in 9
      patients and the mixed form of virus hepatitis (VHB + VHC), in 11 patients.
      Determination of adhesive capacity of neutrophils, production of superoxidase
      anion in the nitro blue tetrazolium (NBT) test, activity of myeloperoxidase (MPO)
      and acidic phosphatase (AP), the amount of cation proteins (CP) was made. Most
      pronounced functional dysbalance of neutrophil leukocytes and considerable
      changes in biochemical characteristics of the activity of the infectious process
      in patients with the mixed form of virus hepatitis were established. These data
      demonstrated that in acute virus hepatitis B and C at the peak of the disease
      such characteristics of the functional activity of neutrophils as results of the
      NBT test, the activity of MPO and AP, as well as the amount of CP, were highly
      informative.

PMID- 11236503
TI  - [Features of overall and local immunity in patients which chronic rhinitis of
      different etiology].
AB  - The systemic and mucosal immune status in 50 patients with all-year-round
      allergic rhinitis (AYRAR), chronic infectious rhinitis (CIR) and non-atopic
      eosinophilic rhinitis (NER) was evaluated. Patients with concomitant pathology
      (bronchicial asthma, chronic bronchitis, sinusitis, etc.) were found to have
      changes in the systemic immunity. Patients with AYRAR and CIR had a high level of
      SIgA in their nasal secretions, and in the latter--also an elevated level of
      local IgG NER patients exhibited a considerable decrease in local production of
      immunoglobulins. In the nasal secretions of AYRAR and CIR patients high
      phagocytic activity of neutrophilis was established in the nitro blue tetrazolum
      test. The results of the study showed the expediency of determination of immune
      disturbances in these patients with a view to administration of immunocorrective
      therapy.

PMID- 11236504
TI  - [Biological properties of Vibrio cholerae as a part of epidemiologic surveillance
      of cholera].
AB  - Systematic dynamic surveillance of the complex of biological properties of V.
      cholerae makes it possible to find out specific features of this infective agent,
      to improve diagnostics and to use the data thus obtained for epidemiological
      surveillance on cholera. The study of the complex of biological properties of V.
      cholerae O1, its ecological relationships and interactions give evidence to
      assert that microbiological aspects as one of the primary tasks in monitoring
      water ecosystems, as well as the necessity of surveillance on strains isolated
      from humans. Different properties of V. cholerae should be determined
      irrespective of the object, time and territory of their isolation in the process
      of epidemiological surveillance on cholera.

PMID- 11236505
TI  - [Causes of para-allergy to tuberculin].
AB  - Experiments on 56 rabbits infected with microorganisms of the genera
      Mycobacterium, Nocardia and Rhodococcus revealed that in response to the action
      of different antigens used T and B systems of immunity induced synthesis of
      antibodies reactive with nonspecific antigens (mycobacterial antigens,
      tuberculin). In some cases the statistically significant correlation between the
      dynamics of blast transformation and the specific lysis of lymphocytes in animals
      with Nocardia and Rhodococcus infections (in comparison with the controls) was
      determined when P.P.D. tuberculin was used as specific antigen. In the rabbits
      sera infected by Nocardia and Rhodococcus complement-fixation and
      hemagglutination antibodies to mycobacterial antigens were detected. These
      rabbits also exhibited skin reaction to P.P.D. tuberculin. The presence of common
      group-specific antigens in Nocardia and Rhodococcus, as well as in mycobacteria,
      determined the capacity of the former to sensitize experimental animals to
      tuberculin, with should be taken into consideration in making the allergic test
      to tuberculosis.

PMID- 11236506
TI  - [Immunocorrecting and protective effect of proteolytic enzymes on antibody
      formation in mice in staphylococcal infection and antibiotic treatment].
AB  - The impact of proteolytic enzymes on the humoral immune response, survival rate
      and mean survival time of mice, infected with S. aureus culture and receiving
      antibiotics was studied. Infection with staphylococcal suppressed the formation
      of antibodies to sheep red blood cells. Ampicillin made this immunosuppression
      even more pronounced, while gentamicin produced practically no effect on the
      degree of immunosuppression in the infected animals. Proteolytic enzymes
      terrilytin and terridecase exhibited immunocorrecting properties when used in
      combination with antibiotics. Terridecase, the immobilized form of the enzyme
      proved to have the highest activity. In experimental generalized staphylococcal
      infection all preparations under study produced a protective effect. The maximum
      effect was noted after the use of ampicillin in combination with terridecase.

PMID- 11236507
TI  - [Level of Tx1- and Tx2-type cytokines in blood sera of hepatitis C patients].
AB  - The content of cytokines of type Tx1 (IL-2 and IFN-gamma) and type Tx2 (IL-4) in
      blood sera of 132 patients with hepatitis C and the combined form of hepatitis B
      + C was studied. For control, blood sera taken from healthy donors were used. A
      significant increase, in comparison with the control, in the content of IL-4 in
      all subgroups of the patients was registered. The content of IFN-gamma reached
      the maximum level in patients with acute hepatitis C with the positive result of
      the polymerase chain reaction (PCR) for the virus (216.4 and 46.4 pg/ml
      respectively) and was somewhat lower in acute hepatitis C with the negative PCR
      result (77.7 and 9.6 pg/ml), mean while in the chronic course of hepatitis C
      these data were within the limits of control values irrespective of the results
      of PCR. In case of mixed infection in the acute clinical form a significant
      increase in the concentration of IFN-gamma (34.4 pg/ml) in comparison with the
      control (25.3 pg/ml) was observed. The content of IFN-gamma in patients with
      acute hepatitis C and the positive result of the test for NS antibodies also
      reached the maximum level (207.3 and 42.7 pg/mg respectively). But in contrast to
      hepatitis C in the acute form with the negative results of PCR in patients with
      hepatitis C in the acute form and the negative results of the NS test these data
      were within the limits of control values, as well as in the chronic course of
      hepatitis C irrespective of the results of the NS antibodies serum test. In case
      of mixed infection a significant increase in the concentration of IFN-gamma was
      registered in the subgroup of patients with the acute form of NS+ (39.9 pg/ml).
      The data obtained in this study were indicative of significant changes in the
      serum profile of serum cytokines of types Tx1 and Tx2 in different forms and
      courses of virus hepatitis. This makes it possible to believe that the
      chronization of the process was associated with the prevalence of the Tx2
      function.

PMID- 11236508
TI  - [Comparative study of parietal and lumen microflor in the large intestine in
      experiments on mice].
AB  - The methodological aspects of the study of the microflora of the parietal mucous
      layer (parietal mucin) of the large intestine is discussed; the study is
      difficult because the mucin layer is thin closely associated with epithelium and
      the impossibility of the mechanical separation of this layer from the epithelium
      without damaging the latter is possible. The method of homogenization fails to
      determine of the composition of parietal mucin proper. Such possibility becomes
      real after the dissolution of mucin and obtaining the suspension of microbial
      cells. As experimentally shown in vitro, urea solution, reducing disulfide bonds,
      effectively depolymerized mucin and exhibited no antibacterial and cytolytic
      activity. With the use of urea treatment, microflora of parietal mucin of the
      large intestine was studied on 44 non-inbred mice. This newly developed method
      was shown to have higher resolution in comparison with the traditional one
      (homogenization). Some qualitative and quantitative characteristics of the
      microflora of parietal mucin were established. In the same group of mice the
      study of fecal microflora was made and compared with microflora of parietal
      mucin.

PMID- 11236509
TI  - [Microbiocenosis of the large intestine in acute complicated pneumonia in
      children].
AB  - Fifty-six children of early age with pneumonia developed on the background of
      frequent respiratory infections were placed under observation. In 91.1% of these
      cases microecological disturbances in the intestine were detected, 46.6% of the
      patients having third-degree dysbacteriolysis. In such cases it is more correct
      to regard the "intestinal" syndrome as the clinical manifestation of disturbances
      in the biocenosis of the intestine, the state of its microflora. Intestinal
      dysbacteriosis aggravates the course of acute aggravated pneumonia in children
      and requires the inclusion of special therapy aimed at normalizing intestinal
      microflora.

PMID- 11236510
TI  - [Intestinal dysbacteriosis in different age groups of residents of Kemerovo].
AB  - The state of microflora of the large intestine in 877 persons of different age
      groups in Kemerovo was studied. The study revealed that intestinal
      dysbacteriolysis of various degrees of severity was rather widely spread among
      the residents of the city. The main groups of risk, found to comprise young
      children, adolescents and people above 60 years of age, were established.

PMID- 11236511
TI  - [Intestinal microecology of the adult population of Mongolia, Switzerland, and
      Russia].
AB  - The study of intestinal microflora was made in clinically healthy young adults
      living in rural areas of Mongolia, in Russia (Moscow) and in Switzerland, as well
      as in Swiss citizens of elderly age groups (55-68 and 87-94 years). Essential
      differences in the quantitative and qualitative characteristics of intestinal
      microflora both in the inhabitants of different countries as well as in people
      belonging to different age groups in the same country were established. The
      results of the study demonstrated the expediency of working out the criteria of
      the norm for intestinal microflora both for the population of different countries
      and for people living in the same country, but belonging to different age groups.

PMID- 11236512
TI  - [Antimicrobial activity of hyaluronic acid].
AB  - In this work the biological activity of hyaluronic acid (HA), isolated from fowl
      crests, is evaluated. The data on the physico-chemical analysis of HA are
      presented. The preparation obtained is characterized by a high content of the
      main substance and high relative viscosity. Sterilization conditions for HA,
      depending on the degree of microbial contamination of the preparation, were
      carried out. As revealed in this study, irradiation with a dose of 1.0 Mrad is
      sufficient for obtaining a sterile preparation. HA has been found to possess
      inhibiting activity with respect to Pseudomonas.

PMID- 11236513
TI  - [Correction of immunologic reactivity depending on ABO system antigens in
      patients with purulent infections of soft tissue and shigellosis].
AB  - The immunological study of more than 300 patients with purulent infection of soft
      tissues and shigellosis was carried out. The character and manifestation of the
      immunocorrecting action of sodium nucleinate were found to depend on the antigens
      of the AB0 system, which proved to be different in various type of pathology.

PMID- 11236514
TI  - [Combined focus of tick-borne encephalitis, tick-borne rickettsiosis and
      tularemia in the habitat of Haemaphysalis concinna in south central Siberia].
AB  - For the first time in the Krasnoyarsk region the population Haemaphysalis
      concinna ticks were found to be infected with the causative agents of three
      natural focal tick-borne infections--tick-borne encephalitis, tick-borne
      rickettsiosis and tularemia. The existence of the combined natural focus of these
      three infections has been confirmed by epidemiological data. Ticks Dermacentor
      nuttalli also play a similar role in combined foci of tick-borne encephalitis and
      tick-borne rickettsiosis in these focal territories.

PMID- 11236515
TI  - [Multiplication of Listeria in milk products].
AB  - The results of the evaluation of the multiplication dynamics of Listeria cells in
      milk and Bifidok, a lactic acid product, are presented. The samples were
      inoculated on thioglycol agar and studied at different exposure time after
      incubation at 37 degrees C, 20 degrees C and 4 degrees C. The study revealed the
      intensive multiplication of Listeria cells in milk, also during storage in a
      household refrigerator. The presence of bifidobacteria mixed with kefir-producing
      culture in dairy products was shown to essentially inhibit the growth of Listeria
      cells which were not detected by bacteriological techniques on day 7.

PMID- 11236516
TI  - [Role of bacterial toxins in pathogenesis of hemolytic-uremic syndrome, caused by
      enterohemorrhagic Escherichia].
AB  - The pathogenesis of the hemolytico-uremic syndrome (HUS) caused by
      enterohemorrhagic E. coli (EHEC) has been studied previously rather completely.
      HUS is characterized by the signs of microangiopathic hemolytic anemia,
      thrombocytopenia with renal lesions and manifestations of transient disturbances
      in the functions of the central nervous system. The adherence of EHEC to
      enterocytes was found to occur in the terminal section of the ileum and the large
      intestine. This process is realized with involvement intimin, EHEC outer membrane
      protein. Shiga-like toxins (SLT) produced by EHEC are the leading factor of their
      pathogenicity. The mechanism of the toxin translocation through enterocytes is
      not yet clear, still there is no doubt that SLT penetrates into the systemic
      blood stream. This is indicated by the results of histopathological studies it
      possible to find the toxin traces on the membranes of endothelial cells of blood
      vessels. The study reveals that the cells of the vascular epithelium are highly
      sensitive to SLT. These cells carry receptors Gb3, also known as CD77, on their
      membranes. Enterohemolysin, serine protease, causing disturbances in the barrier
      function of the intestine, can be regarded in the pathogenesis of hemorrhagic
      colitis which develops as the result of the damaging action of EHEC and the above
      mentioned toxins. This leads to the increased level of blood systemic bacterial
      lipopolysaccharides, which may play, in combination with the action of SLT, an
      important role in the development of multi-organ pathology in HUS patients.

PMID- 11236518
TI  - [History, principles of construction of combined vaccine and problems of vaccine
      prophylaxis with their use].
AB  - This problem article deals with modern trends in the creation and use of combined
      vaccines, the advantage and drawbacks of multicomponent preparations. The data on
      competition, interference and synergism in the action of individual components
      making up combined vaccines, on the cellular and molecular mechanisms of the
      interaction of antigens are presented. Specific features of the development of
      immunity induced by complex vaccines with due regard to the action of genetic and
      phenotypic signs, as well as the formation of humoral and cell-mediated immunity.
      The priority of Russian researchers in the development of the first combined
      vaccines is pointed out. On the basis of theoretical knowledge and accumulated
      practical experience the main principles of the construction and properties of
      combined vaccines have been formulated.

PMID- 11236517
TI  - [Drug resistance of Staphylococcus aureus strains, isolated from children with
      intestinal dysbacteriosis].
AB  - The level of antibiotic-sensitivity of 73 S. aureus strains isolated from
      children with dysbacteriosis of the large intestine in an outpatient clinic was
      determined. The isolation rate of polyresistant strains was 44%. Methicillin
      resistant S. aureus (MRSA) were isolated from 25 children (34.2%). 60% of MRSA
      strains could not be typed with the international set of phages. Among the
      strains capable of being lyzed by the phages the representatives of phage groups
      3 and 4 prevailed. All MRSA strains were sensitive to vancomycin, 84-88% of the
      strains were sensitive to chloroamphenicol, rifampicin, spiramycin and neomycin,
      80% of the strains were sensitive to fusidin and phosphomycin. The level of
      sensitivity of methicillin-sensitive S. aureus strains (MSSA) to different groups
      of antistaphylococcal antibiotics was higher. 36-64% of MRSA strains and 21-27%
      of MSSA strains were resistant to the action of curative bacteriophages. The
      suppression of obligate microflora was the risk factor in the development of
      staphylococcal infection of the gastrointestinal tract in children.

PMID- 11236519
TI  - [Modern features of the epidemiology and prophylaxis of influenza].
AB  - Modern concepts concerning influenza pandemics and epidemics in different
      countries of the world are presented. The influenza epidemics of the last decade
      in different countries of the world and their specific features linked with the
      "drifting" variability of influenza virus have been analyzed. Information on
      influenza morbidity during the last 30 years is given; on the basis of this
      information the role of vaccinal prophylaxis and mainly the mass vaccination of
      school children and students, is shown. The results of the efficacy of such
      vaccines as live influenza vaccine, American split vaccine, Russian live
      recombinant vaccine and Grippovac (1995-1996), as well as new-generation vaccine
      Grippol (1998), are presented. The prospects of the combined use of specific and
      unspecific prophylaxis have been determined.

PMID- 11236520
TI  - [Starvation of bacteria as a stress caused by substrate limitation].
AB  - The analysis of literature has made it possible to establish the priority of
      Russian research works made in the 1970-80s on the subject of starvation of
      bacteria caused by substrate limitation as well as research made in the 1990s
      concerning starvation of bacteria. This state is characterized by synthesis of
      additional proteins, so-called stress proteins, which not only ensure the
      survival of bacteria under the conditions of substrate limitation, but also
      protect them from a number of other stressors. In spite of the fact that genetic
      mechanisms regulating the synthesis of some stressor proteins have been revealed
      their significance for microbiological technology is not yet clear.

PMID- 11236521
TI  - [Hemodialysis after injection of contrast media--useful, harmful or
      ineffective?].

PMID- 11236522
TI  - [Contrast media-induced kidney failure cannot be prevented by hemodialysis].
AB  - BACKGROUND AND OBJECTIVE: Radiographic contrast media (CM) administration causes
      a decline in renal function, especially in patients with pre-existing renal
      impairment. The value of CM removement by dialysis to prevent radiocontrast
      induced nephropathy (RCIN) has not been established yet. The present study was
      designed to investigate the influence of haemodialysis on renal function in
      patients with preexisting renal failure receiving CM for various purposes.
      PATIENTS AND METHODS: 15 patients with reduced renal function (mean serum
      creatinine concentration 2.7 +/- 0.2 mg/dl) were randomly assigned to receive
      either haemodialysis for 2-3 hours, started as early as possible after
      administration of CM (106 +/- 25 minutes), or conservative treatment. Serum
      creatinine and iodine concentrations were measured over 5 days. RESULTS: The
      percentile creatinine increase on days 2 and 3 after CM application was higher in
      the dialysed group. The rate of RCIN (defined as a serum creatinine increase of
      greater than or equal to 0.5 mg/dl within 48 h after administration of CM) was
      significantly higher in the dialysed group (43% in the haemodialysis group and
      13% in the group on conservative treatment, respectively). Iodine concentration
      declined earlier in the dialysed group. CONCLUSION: Our data indicate that
      haemodialysis performed within two hours after CM application did not prevent the
      occurrence or the outcome of RCIN in patients with renal failure. In some
      patients haemodialysis even seems to have worse effects regarding the development
      of RCIN.

PMID- 11236523
TI  - [Symptoms of primary endocardial fibroelastosis in a young adult].
AB  - HISTORY AND ADMISSION FINDINGS: A 21-year-old woman with known endocardial
      fibroelastosis diagnosed when aged 3 months was admitted because of progressive
      dyspnoea. The physical examination revealed symptoms of heart failure, with
      pulmonary rales, mild hepatomegaly, and tachyarrhythmia. INVESTIGATIONS: The
      electrocardiogram showed atrial fibrillation, complete right bundle branch block
      and right ventricular hypertrophy. Echocardiography indicated hypertrophy and
      dilatation of the right ventricle (61 mm) with tricuspid regurgitation and
      hypoplasia of the left ventricle. Heart catheterization confirmed pulmonary
      hypertension (60/46 mmHg) as well as dilatation and hypokinesia of the right
      ventricle. Right ventricular biopsy showed severe myocardial hypertrophy
      resulting from secondary pulmonary hypertension, while no evidence of myocarditis
      or idiopathic dilated cardiomyopathy was found. TREATMENT AND COURSE: Symptoms of
      heart failure improved under medical treatment with digitalis, angiotensin
      converting enzyme inhibitor and diuretics. CONCLUSION: Primary endocardial
      fibroelastosis of the contracted type must be included in the differential
      diagnosis of heart failure occurring in young adults.

PMID- 11236524
TI  - [Gastrointestinal stromal tumor: individualized treatment for a special class of
      tumors].
AB  - HISTORY AND ADMISSION FINDINGS: Case 1: A 36-year-old woman was admitted because
      of dizziness and weakness. Her skin and mucosae were pale. There was rather dark
      stool on the gloved finger at rectal examination, but the patient had not noticed
      any tarry stools. Case 2: An 89-year-old man in excellent general condition
      presented with dyspepsia. Physical examination was unremarkable except for a
      small epigastric hernia. INVESTIGATIONS: Endoscopy in Case 1 revealed, at the
      lesser curvature of the gastric antrum, a submucous tumour covered by a slightly
      haemorrhagic mucosal erosion. In Case 2 endoscopy similarly revealed an antral
      submucous tumour. There was no evidence of metastasis in either case. TREATMENT
      AND COURSE: Exploratory laparotomy was performed in both patients. A subtotal
      gastric resection with gastrojejunostomy was undertaken in Case 1, a submucous
      excision via an anterior gastrostomy in Case 2. In both cases histology showed a
      gastrointestinal stromal tumour, but its benignity could not be firmly
      established even after detailed immunohistological examination. CONCLUSION:
      Gastrointestinal tumours are rare. Although they have particular
      immunohistological characteristics their benignity cannot usually be definitively
      established even on the excised specimen. Because more extensive resection does
      not increase survival time, a resection margin of 1-2 cm is considered adequate.
      Neither radio- nor chemotherapy are successful. Life-long follow-up is indicated
      because the tumor's uncertain benignity.

PMID- 11236525
TI  - [Toxic epidermal necrolysis (drug-induced Lyell's syndrome). 2. Treatment].

PMID- 11236526
TI  - [Epidural spinal cord stimulation in the treatment of therapy-resistant angina
      pectoris].

PMID- 11236527
TI  - [Short, structured and rapidly transmitted: the "optimal" doctor's letter].

PMID- 11236528
TI  - [Antibiotic treatment in myocardial infarction?].

PMID- 11236529
TI  - [Itching in hyperparathyroidism].

PMID- 11236530
TI  - [Endoscopic planning of percutaneous endoscopic gastrostomy (PEG-/PEJ-probe) for
      enteral nutrition].

PMID- 11236531
TI  - [Prognostic value of the number of involved nodes after neck dissection in
      oropharyngeal and oral cavity carcinoma].
AB  - PURPOSE: To evaluate the relationship between the number of positive nodes and
      probabilities of locoregional control and survival in patients with invasive
      squamous cell carcinomas of the oral cavity and oropharynx. MATERIAL AND METHODS:
      Between 1976 and 1993, we treated with curative intent 183 patients (median age:
      56 years; standard deviation: 10 years). Seventy-nine patients (43%) had
      oropharyngeal primary invasive carcinoma and 104 (57%) had oral cavity (excluding
      the lip) primary invasive carcinoma. Patients with simultaneous primary lesion or
      visceral metastases were excluded from the analysis. All the patients had neck
      dissection with at least six nodes to analyse. One-hundred fifty-nine patients
      (87%) underwent resection of the primary lesion and 158 (86%) were treated
      postoperatively with external beam irradiation alone or combined with
      interstitial implant (median dose: 60 Gy; standard deviation: 10 Gy). Average
      follow-up was 52 months. RESULTS: The overall 5-year survival rate using the
      Kaplan-Meier method was 42.6%. The 5-year survival rates were 60.0% when lymph
      nodes were histologically negative, 39.5% when one lymph node was positive, 28.0%
      when two lymph nodes were positive and 24.4% when three or more lymph nodes were
      positive (P = 0.0004). The number of positive nodes did not significantly
      influence the specific disease-free survival and locoregional control rates.
      CONCLUSION: Patients with one or more positive neck nodes must have postoperative
      treatment.

PMID- 11236532
TI  - [Production process in external radiotherapy and cost-inducers research in 2
      hospital units].
AB  - PURPOSE: To analyse the process of outpatient radiation therapy by dividing it
      into elementary acts, and to determine the cost-inducers (staff and machine time,
      equipment) in order to enhance the value of radiotherapy activity. MATERIAL AND
      METHODS: The care process was analysed from 1 June 1997 to 1 September 1997, in
      two institutions (Centre hospitalo-universitaire de Saint Etienne and centre de
      Lutte contre le Cancer de Lyon), in terms of consumption of human and equipment
      means, representing a cost for the care institution. The valorization was
      expressed in physics units for material means, and in time units for human and
      heavy equipment. Parameters able to modify the consumption of means had been
      defined. The following data had been collected for each activity: patient
      characteristics, characteristics of the process, specific parameters of each
      activity, data related to the care staff and care unit. RESULTS: The importance
      of the specific data of each activity was noteworthy. Two criteria modified the
      valorization: the complexity level of dosimetry and inclusion in a research
      trial. Total body irradiation and conformal radiotherapy were well
      individualized. There was no difference between the two care units. The lack of
      cost-inducers for the 'immobilization-simulation' activity reflects the large
      diversity of practice, and requires a global analysis of the 'treatment
      preparation' process. CONCLUSION: The cost-inducers found in this study could
      permit the elaboration of the 'relative cost index' in radiation therapy. (The
      results obtained must be validated in other types of care units.) These relative
      cost indexes would describe the various phases of the treatment, such as
      treatment preparation, dosimetry, treatment, quality control. This approach is
      currently used by workshops in PMSI (Programme de Medicalisation des Systemes
      d'Information) and NGAP (Nomenclature Generale des Actes Professionnels).

PMID- 11236533
TI  - ["How are patients treated in the year 2000 and where does progress come from?"].

PMID- 11236534
TI  - [Slice imaging in bronchial cancer].

PMID- 11236535
TI  - [A revolution in pneumology: positron-emission tomography].

PMID- 11236536
TI  - [Respiratory carcinogenesis: epidemiologic and behavioral features, and evolution
      of concepts].

PMID- 11236537
TI  - [Results of a randomized prospective trial comparing postoperative abdominopelvic
      radiotherapy with postoperative chemotherapy in early ovarian cancer].
AB  - PURPOSE: In a prospective randomized trial, our aim was to evaluate and compare
      the tolerance and efficacy of postoperative radiotherapy and chemotherapy in the
      treatment of early ovarian cancer. MATERIAL AND METHODS: Between 1990 and 1996,
      150 patients with ovarian cancer stage IA, IB grades G2-3, and all patients
      classified IC and IIA, who did not have evidence of residual disease after
      surgery, were randomized to two treatment branches: radiotherapy or chemotherapy
      (CH). In the radiotherapy branch (76 patients), a whole abdomen irradiation of 30
      Gy in 24 fractions over 5 weeks, with a pelvic boost to 50 Gy, was delivered. In
      the chemotherapy branch (74 patients), there were six series of polychemotherapy
      separated with 3-weeks interval. In each series patients received association of
      cisplatin (50 mg/m2, d1), adriamycin (50 mg/m2, d1) and cyclophosphamide (500
      mg/m2, d1). RESULTS: The tolerance of the treatment was good and comparable in
      both groups. In the radiotherapy branch, three late grade G3 intestinal
      complications were observed (three bowel obstructions, which required surgery in
      two cases). The actuarial survival rate without evidence of disease was 81% at 5
      years for both groups. In our series we found that histological grade had the
      strongest influence on survival prognosis; it was the only significant factor in
      a multivariate analysis. Patients with grade G3 tumors had the worst survival.
      CONCLUSION: These data suggest that efficacy of postoperative radiotherapy and
      chemotherapy administered to our patients with early ovarian cancer gave
      approximately identical results.

PMID- 11236538
TI  - [Surgery of non-small-cell bronchial carcinoma. Indications. Limitations.
      Mediastinoscopy. Report of 2086 personal cases and review of the literature].

PMID- 11236539
TI  - [Neoadjuvant approach in non-small-cell bronchial cancer. Neoadjuvant
      chemotherapy].

PMID- 11236540
TI  - [Neoadjuvant chemoradiotherapy in the treatment of non-small-cell bronchial
      cancer].

PMID- 11236541
TI  - [Unresectable bronchial cancer: which treatment and which therapeutic options?
      Lessons from the past decade].

PMID- 11236542
TI  - [Chemotherapy of non-small-cell bronchial cancer].

PMID- 11236543
TI  - [Locally advanced non-small-cell bronchial cancer: role of exclusive
      chemoradiotherapy].

PMID- 11236544
TI  - [Chemotherapy of stage IV non-small-cell bronchial cancer].

PMID- 11236545
TI  - [IFCT --French Intergroup of Thoracic Cancerology: presentation, protocols].

PMID- 11236546
TI  - [19th Congress of the European Society for Therapeutic Radiology and Oncology.
      Istanbul, September 19-23, 2000].

PMID- 11236547
TI  - [Proceedings of the 42nd meeting of the American Society of Therapeutic Radiology
      and Oncology (ASTRO). Boston, October 22-26, 2000].

PMID- 11236548
TI  - [Favourable and unfavourable effects on long-term survival of radiotherapy for
      early breast cancer: an overview of the randomised trials].

PMID- 11236549
TI  - [Analysis of disturbances in the three-layer model of associative memory:
      realization of path beating principle upon gradual changes in neuronal activity
      and transmission factors].
AB  - A model is considered in which the activity values, the weights of connections,
      and the transmission factors of neurons are positive, the connections are chosen
      by chance and are symmetric regarding the layer of associative neurons. Formulas
      were obtained for the mathematical expectation and the dispersion of activity
      values at the model outputs in the initial state and during the associative
      readout after recording the associations of input pairs and the association of
      the activity vector with the input-mark with two methods of recording. It was
      shown that (unlike quasiholographic models) in the beating model there arise
      hampering additions to the mathematical expectation, some of them being difficult
      to remove. Dispersive disturbances during vector recording considerably exceed
      the disturbances arising in quasiholographic models.

PMID- 11236550
TI  - [Photoinduced resonance phenomena in the human electroencephalogram as a function
      of frequency, intensity, and duration of stimulation].
AB  - The features of resonance phenomena in high-resolution EEG structure were
      analyzed for two intensities and three values of duration of exposure to 20
      constant frequencies of intermittent photic stimulation in a range of 1-20 Hz
      with 1 Hz steps. It was shown that with a 6 s step duration, an irregular
      activation of multiple spectral EEG components for both light intensities occurs.
      With longer durations (12 and 18 s) of fixed-frequency stimulation, the EEG
      reactions are of resonance nature. Low-intensity flashes cause only the resonance
      activation of the intrinsic oscillator in the range of dominant alpha-EEG
      frequency. During a more intensive stimulation, the resonance EEG phenomena are
      observed for the whole range of stimulation frequencies. The interval of 6-12 s
      is supposed to be the relaxation period for a system of brain electrical activity
      generation. After this time, the low-intensity stimuli cause the adaptation of
      the system to light, whereas more intensive flashes cause more pronounced
      resonance EEG phenomena and physiological effects.

PMID- 11236551
TI  - [Activation and inhibition of the gravitropic response in the flax stem segments
      exposed to the permanent magnetic field with magnetic density ranging from 0 to
      350 microT].
AB  - It was found that the rate of gravitropic bending in apical segments excised from
      4-day-old etiolated seedlings of flax Linum bienne is strongly and nonlinearly
      dependent on the value of the magnetic flux density of a static magnetic field,
      BDC, in the range from 0 to 350 microT. The gravitropic bending is stimulated at
      0 < or = BDC < or = 2 microT and 200 < or = BDC < or = 350 microT but is
      inhibited at 100 < or = BDC < or = 170 microT relative to control samples being
      in the magnetic field of the Earth equal to 46.5 microT.

PMID- 11236552
TI  - [Effects of extremely weak alternating magnetic fields on the plant
      gravitropism].
AB  - It was shown that the rate of gravitropic response in apical segments excised
      from the 4-day-old seedlings of flax (Linum bienne) may be substantially
      influenced by combined magnetic fields (CMF) of two different types: 1) CMF tuned
      to the parametric resonance for Ca2+; 2) CMF containing extremely weak
      alternating component with the values of magnetic density ranging from 10(-6) to
      10(-10) T. Our experimental data indicate that CMF affect the gravitropic
      response via at least two different mechanisms. The first one corresponds to the
      ion parametric resonance well established earlier in studies with test-systems
      prepared from animals. The origin of the bioeffects induced by CMF containing
      extremely weak alternating component remains to be established.

PMID- 11236553
TI  - [Effect of centimeter microwaves on the antibody production in mice].
AB  - The effect of low-intensity microwaves (8.15-18 GHz, 0.3 or 1 microW/cm2, 1.5 h
      daily for 30 days) on antibody production in healthy male NMRI mice after
      immunization with affinity-purified carboanhydrase isolated from bovine
      erythrocytes with and without Freund's adjuvant was studied. It was found that
      exposure to microwaves leads to an increase in the concentration of antibodies in
      blood plasma, the stimulating effect being more pronounced in the primary immune
      response. It is assumed that the effect of enhancement of the immune response by
      the action of centimeter microwaves can be used in the adjuvant therapy.

PMID- 11236554
TI  - [Effect of centimeter microwaves and the combined magnetic field on the tumor
      necrosis factor production in cells of mice with experimental tumors].
AB  - The effect of fractionated exposure to low-intensity microwaves (8.15-18 GHz, 1
      microW/cm2, 1.5 h daily for 7 days) and combined weak magnetic field (constant 65
      1 microT; alternating--100 nT, 3-10 Hz) on the production of tumor necrosis
      factor in macrophages of mice with experimental solid tumors produced by
      transplantation of Ehrlich ascites carcinoma was studied. It was found that
      exposure of mice to both microwaves and magnetic field enhanced the adaptive
      response of the organism to the onset of tumor growth: the production of tumor
      necrosis factor in peritoneal macrophages of tumor-bearing mice was higher than
      in unexposed mice.

PMID- 11236555
TI  - [Electron structure of plastoquinone and coupling of electron and proton
      transport in thylakoids of the higher plants].
AB  - The energy dependence on hydrogen position for a system, consisting of
      plastoquinone (in different redox states) and histidine molecules was studied.
      The distance between the atoms forming the hydrogen bond, an oxygen of the
      quinone molecule and a nitrogen of histidine, was supposed to be fixed. It was
      shown that for neutral quinone the total energy is minimal when the hydrogen is
      bound to histidine; for reduced quinone, the probability of hydrogen binding to
      quinone and histidine is approximately equal (so that a hydrogen bond is formed)
      and on secondary reduction of plastoquinone, the hydrogen binds to it.

PMID- 11236556
TI  - [Theoretical study of the pulse method for the quenching analysis of photosystem
      II fluorescence].
AB  - The kinetics of photochemical (qQ) and nonphotochemical (qE) fluorescence
      quenching during induction was studied in terms of the earlier developed
      theoretical model of photosynthesis. Photochemical and nonphotochemical quenching
      was calculated from the parameters of fluorescence induction upon simultaneous
      excitation with continuous light and by high-intensity light pulses by the method
      used in a PAM fluorometer. It is shown that the fraction of closed reaction
      centers during the pulse can change in the course of induction. In consequence,
      even when none of supposed mechanisms of photochemical quenching is taken into
      account, the value of qE during induction varies and is not equal to zero.

PMID- 11236557
TI  - [Effects of hydrocortisone and insulin on the electrokinetic potential of
      hepatocyte nuclei].
AB  - The electrokinetic potential of liver cell nuclei of rats after the in vivo
      separate and joint injection of hydrocortisone and insulin was determined. It was
      shown that the steroid induces a significant elevation of the value of
      electrokinetic potential while insulin does not change this parameter. An
      insignificant elevation of the potential by the joint action of the hormones was
      found, which apparently is indicative of the antagonism between hydrocortisone
      and insulin.

PMID- 11236558
TI  - [Effects of plant growth regulators ambiol and phonk: biolphysical aspects].
AB  - The antioxidative activity of two plant growth promoters, ambiol and phonk, in a
      model system of photo-induced glycyltriptophane oxidation was measured. It was
      shown that ambiol has a significant antioxidative activity, whereas phonk is a
      weak antioxidant. The effects of these compounds on DNA conformation were studied
      in vitro and in vivo (on wheat seed shoots). In vitro ambiol had a stronger
      effect as compared with phonk, whereas in vivo the latter produced a more
      essential effect than ambiol. The assumption was done that both compounds affect
      indirectly the genome expression activity. Possible mechanisms of biological
      activity of each compound are discussed.

PMID- 11236559
TI  - [Parameters of binding of fluorescent probe pyrrone red with human serum
      albumin].
AB  - The constant of binding of a new fluorescent probe pyrrone red to human serum
      albumin (Kb = 4.7.10(5) M-1) and the number of binding sites (N = 2) were
      determined by the method of double fluorimetric titration at a Fex/Fem intensity
      ratio of 560/625 nm. The affinity of pyrrone red for albumin was by 20% lower
      than that of 8-anilinonaphthalenesulfonate and 2.4 times higher than that of
      another probe K35. Thus, pyrrone red is almost identical to
      amlinonaphthalenesulfonate in affinity for albumin and can be considered as a
      long-wavelength "red" analogue of anilinonaphthalenesulfonate.

PMID- 11236560
TI  - [Effect of the bidistilled modified water on bovine serum albumin conformation.
      Fluorescent spectroscopy data].
AB  - It was shown that bidistilled modified water induces a marked decrease in the
      intensity of intrinsic fluorescence of bovine serum albumin and increases the
      binding of this protein to the fluorescent probe 1.8 ANS. These effects can be
      interpreted as a denaturing action of bidistilled modified water on the protein
      and a change in its conformational state, which is probably caused by changes in
      the microenvironment of the protein molecule. In addition, a substantial increase
      in the intrinsic fluorescence of bidistilled modified water, as compared with
      that of distilled water, was found.

PMID- 11236561
TI  - [Y97V substitution in the horse cytochrome c causes accumulation of the
      equilibrium intermediate].
AB  - Equilibrium unfolding experiments on several mutant forms of horse heart
      cytochrome c were performed. By means of absorbance spectroscopy, the
      accumulation of an equilibrium intermediate was revealed upon unfolding of Y97V
      mutant protein, and its structural properties were characterized. The data
      obtained allow one to conclude that the equilibrium intermediate corresponds to
      the earliest kinetic intermediate Ic in cytochrome c folding reaction. A
      comparative analysis of spectral properties of unfolded states of cytochrome c
      induced by urea or guanidine hydrochloride is presented.

PMID- 11236562
TI  - [Biophysics at the turn of the new millenium: perfluorocarbon media and gas
      transporting blood substitutes].
AB  - The results of 20-year investigations of perfluorocarbon gas-transporting
      emulsions for biological and medical applications performed by russian
      biophysicists together with chemists and clinicists are reviewed. As a result of
      these investigations, the blood substitute perftoran was created. Now this
      commercial blood substitute has different applications in clinics of Russia and
      other countries.

PMID- 11236563
TI  - [A three component water-biopolymer-ions system: a model for molecular mechanisms
      of osmotic homeostasis].
AB  - It is shown that water-ion homeostasis in a water-biopolymer-salt system is
      realized when proportion of the concentrations of the components changes in the
      definite range. The mechanism of instantaneous osmotic regulating reaction is
      discussed, which is based on the ability of the system to physicochemical
      redistribution of the components of the solution and the formation of
      supramolecular structures in the form of dynamic biopolymer clusters.
      Quasiequilibrium biopolymer<-->cluster leads to changes in the properties of the
      hydration water phase that provide the stabilization of water activity and the
      ability of hydration water to dissolve electrolyte ions. It regulates osmotic
      pressure and surface tension in water-protein matrix. This process supports a
      balance of stabilizing and destabilizing forces that affect protein structure and
      determine its functional activity.

PMID- 11236564
TI  - [Free radical reactions and energy transformation in microsome membranes.
      Arrhenius equation for the monooxygenase reaction].
AB  - The mechanism of coupling of the oxidation and activation of membrane enzymes was
      considered. It is obvious that microsomal monooxygenase uses the energy of NADPH
      oxidation for the activation of the terminal agent--cytochrome P-450. However,
      till now the mechanism of the transformation of this energy has not been
      discussed. It is supposed that the coupling process includes transformation of
      oxidation energy to kinetic energy, the energy of lipid pulsations. The mechanism
      proposed by us and the mechanism of energy transformation according to Mitchell
      are two independent mechanisms, both being of fundamental importance for
      biochemistry and biophysics of membranes. One approach uses the dielectric
      properties of membrane, and the other is based on the ability of hydrocarbon
      chains of phospholipids for rotamerization. A new empirical Arrhenius equation
      for membrane processes is offered. It accounts for the ability of membrane to
      reserve the energy in kinetic form (internal temperature). In conditions when
      membrane proteins cease to be acceptors of energy, the transfer of energy, i.e.,
      transformation of the energy of NADPH oxidation into heat or light, occurs.

PMID- 11236565
TI  - [Membranotropic effects of electromagnetic radiation of extremely high frequency
      on Escherichia coli].
AB  - It was found that "sound" electromagnetic radiations of extremely high
      frequencies (53.5-68 GHz) or millimeter waves (wavelength range of 4.2-5.6 mm) of
      low intensity (power density 0.01 mW) have a bactericidal effect on Escherichia
      coli bacteria. It was shown that exposure to irradiation of extremely high
      frequencies increases the electrokinetic potential and surface change density of
      bacteria and decreases of membrane potential. The total secretion of hydrogen
      ions was suppressed, the H+ flux from the cytoplasm to medium decreased, and the
      flux of N,N'-dicyclohexylcarbodiimide-sensitive potassium ions increased, which
      was accompanied by changes in the stoichiometry of these fluxes and an increase
      in the sensitivity of H+ ions to N,N'-dicyclohexylcarbodiimide. The effects
      depended on duration of exposure: as the time of exposure increased, the
      bactericidal effect increased, whereas the membranotropic effects decreased. The
      effects also depended on growth phase of bacteria: the irradiation affected the
      cells in the stationary but not in the logarithmic phase. It is assumed that the
      H(+)-ATPase complex F0F1 is involved in membranotropic effects of electromagnetic
      radiation of extremely high frequencies. Presumably, there are some compensatory
      mechanisms that eliminate the membranotropic effects.

PMID- 11236566
TI  - [Ristomycin effect on the relationship between electrokinetic parameters of
      erythrocytes and their volume].
AB  - It was found that a decrease in the electrophoretic mobility of erythrocytes by
      the action of ristomycin reflects an increase in their volume.

PMID- 11236567
TI  - [Characteristics of the sound conduction in mammals in the aqueous medium].
AB  - Experimental investigations of sound-conducting tracts in man, seals and dolphins
      are reviewed. Underwater hearing is considered in connection with anatomical,
      morphological, and functional features of species and ecological factors.

PMID- 11236568
TI  - [Secretion-fiber transformation in fibroin of the natural silk by polarization
      optical methods].
AB  - Structural changes in fibroin molecules upon transformation of the secret into a
      fiber were studied by the methods of birefringence in a longitudinal hydrodynamic
      field, optical rotatory dispersion, and circular dichroism. Fibroin fibers were
      obtained by drawing out the secret from the silk-secreting gland of silkworm moth
      Bombux mori. In this process, the formation of a longitudinal hydrodynamic field
      inside the gland was observed. The experimental data obtained make it possible to
      assess the degree of orientation and unfolding of macromolecules, as well as the
      conditions of the alpha-beta structural transition in fibroin chains.

PMID- 11236569
TI  - [Keratin dielectric parameters in the millimeter wavelength range].
AB  - The specific density of human hairs, which are known consist essentially of
      keratin, was measured. Based on the data on the attenuation of millimeter
      radiowaves in hairs, the dielectric permeability of hairs was determined.
      Multiple reflections of waves at the boundary of the hair layer were into
      account.

PMID- 11236570
TI  - [Tendency of the brain to sharp images and geometry of visual illusions].
AB  - Usually, to shift the gaze, our will is needed, which the brain realizes by
      giving an order to the corresponding eye muscles. However, under some conditions,
      the eye movement and the shift of the gaze to perspective can be accomplished by
      non-forced methods, without any active interference of our consciousness.

PMID- 11236571
TI  - [Structure-functional studies of the White sea water and bottom sediments].
AB  - Statistical analysis of dynamic indices of biopolymers enzymatic destruction in
      unstratified and stratified. White Sea water has revealed specific properties of
      protease and amylase activities. We analyzed the component composition and
      hydrolytic enzymatic activities in the surface layer of the bottom sediments (0-2
      cm). The relationship between protease and amylase enzymatic activities in the
      surface sediments with different content of pelite fraction is discussed.

PMID- 11236572
TI  - [An amphiphilic substance inhibits the mollusk capacity to fliter phytoplankton
      cells from water].
AB  - The effect of synthetic anionic surface active substance (SAS) sodium
      dodecylsulfate (SDS, 4 mg/l) on the kinetics of water filtration by mussel
      Mytilus edulis was studied. A suspension of algae Isochrysis galbana was added to
      the vessel with the mussels, and their filtration activity was measured by
      counting the concentration of the algae cells in the experimental vessels. Algae
      concentration was measured every 30 min for an hour and a half. The inhibiting
      effect on the mollusk filtration rate (FR) was qualitatively described. After the
      first 30 min filtration at 4 mg/l initial SDS concentration, the cell density was
      322% of the control. The inhibiting effect was observed later as well. Due to FR
      inhibition in the vessels with the above specified initial SDS concentration, the
      algae cell density was 6.4 and 14.7 times that of the control after 1 and 1.5 h,
      respectively. Thus, SAS SDS can decrease the natural capacity of aquatic
      ecosystems for self-purification and disturb other aspects of ecosystem
      functioning through inhibiting the filtration activity of mussels. The obtained
      data are discussed in the context of environment and hydrosphere protection from
      pollution.

PMID- 11236573
TI  - [The parenchymal cellular composition and extracellular matrix in ontogenesis of
      Triaenophorus nodulus (Cestoda)].
AB  - The cellular composition of parenchyma was studied in the ontogenesis of
      Triaenophorus nodulosus and it was shown that the specialized parenchymal cells
      was absent. The extracellular matrix fibrils were synthesized successively by the
      tegumental cytons and muscle cells. The coracidium basal matrix consisted of
      electron-light and electron-dense layers, and the reticular layer appeared at the
      procercoid stage. Reserve nutrients were accumulated by the musculocutaneous sac
      elements at the procercoid stage and, later, by the glandular and tegumental
      cells. It has been proposed that the parenchyma as an independent histological
      unit is absent, while the parenchymal organization is based on all specialized
      cellular elements that do not lose their typical features.

PMID- 11236574
TI  - [Proliferative activity of the matrix cells in lateral ventricles and granule
      cells in the dentate gyrus of the hippocampus in rats after pre- and postnatal
      alcoholic intoxication].
AB  - The treatment of pregnant and lactating female rats with ethanol inhibits the
      proliferation of matrix cells in the lateral brain ventricles of fetuses and,
      during the early postnatal period, of granule cells in the dentate gyrus and
      cells of the ventral horn of Ammon. A low proliferation rate leads to a decrease
      in the number of neurons forming the granule layer of the dentate gyrus and
      pyramidal neurons in the CA-1 field of the horn of Ammon.

PMID- 11236575
TI  - [Identification and isolation of GTP-binding regulator protein from plasma
      membranes of oocytes from the starfish Asterias amurensis].
AB  - A method for isolating a GTP-binding regulatory protein from starfish oocytes is
      described. The protein consists of three subunits with molecular weights of 40,
      37, and about 8 kDa. It is shown that the 40-kDa subunit has a high GTPase
      activity and is susceptible to ADP-ribosylation by pertussis toxin. The latter
      property of this subunit proved to decrease upon its incubation with
      nonhydrolyzable GTP analogues. These data provide evidence that the plasma
      membrane of starfish oocytes contains a 40-kDa GTP-binding protein with
      properties characteristic of the alpha subunit of the inhibitory Gi protein. The
      role of this protein in the transmembrane signal transmission from the 1
      methyladenine receptor to intracellular effectors is discussed.

PMID- 11236576
TI  - [Chemiluminescence suppression in roots of Pisum sativum L. by various metal
      ions].
AB  - The effect of rare metal ions on the activity of the peroxidase system in Pisum
      sativum L. roots was studied by luminol-dependent chemiluminescence. Trivalent
      ions of scandium, gallium, indium, and lanthanum, to different extents, inhibit
      the chemiluminescence of damaged P. sativum roots. A decreased generation of
      superoxide due to the formation of the complex between metal ions and NADP can
      underlie the inhibited activity of peroxidase system. The possible mechanism of
      inhibition of the peroxidase system activity by metal ions is discussed.

PMID- 11236577
TI  - [Biological model of the accelerated aging. I. Dynamics of spontaneous mutation
      in spermatogenesis in SAM mice (senescence-accelerated mouse)].
AB  - We studied the dynamics of age-related cytogenetic changes in the developing male
      germ cells of mice prone to accelerated senescence (strain SAMP1) and mice
      resistant to accelerated senescence (strain SAMR1) by counting the spermatogonial
      and meiotic micronuclei and testing the defects of the spermatozoon head shape.
      In these animals, the accumulation of germinative mutations has a nonlinear
      pattern. During the entire ontogenesis of SAMP1 mice, the frequency of circular
      spermatids with micronuclei corresponded to the level observed upon induced
      mutagenesis.

PMID- 11236579
TI  - [Breeding biology of the whiskered auklet (Aethia pygmaea): postnesting period].
AB  - This is the third paper on the breeding biology of the whiskered auklet on Buldir
      Island (Aleutian Islands) based on material collected in 1993. Unlike other alcid
      birds, both adult and young whiskered auklets returned to the colony the night
      after the end of the breeding season. From the end of July until the third ten
      day period of August, the number of adult birds that returned to the island was
      at approximately the same level, and then decreased, while the number of young
      birds that returned to the islands markedly varied, and peaks were noted every 5
      8 nights. Adult birds continued to visit all the nest habitats, but not all nest
      chambers were visited equally frequently. In the first and third ten-day periods
      of August, the auklets visited 61% and 19.8% of the nest chambers, respectively.
      It remains unclear whether they were their hosts, or other birds used their nests
      for the next year. The return of adult and young birds to the colony to sleep
      after the breeding season appears to be related to the settled mode of life of
      the whiskered auklet and its feeding near the islands in water perturbations
      caused by tidal currents.

PMID- 11236580
TI  - [Structure and formation of embryonic envelopes in acanthocephalans].
AB  - The data on the fine structure and formation of embryonic envelopes in
      acanthocephalans have been reviewed. Three forms of eggshell organization were
      recognized according to the ultrastructure of the embryonic envelopes which
      corresponded to the taxonomic status of acanthocephalans at the class level. The
      third embryonic envelope is the most variable; its particular structure can be
      considered a morphological adaptation of the eggs to environmental conditions.
      Actual formation proceeds as the subsequent formation of embryonic envelopes and
      intervening space start from the outer envelope. Details of the "fertilization
      membrane" histogenesis are discussed.

PMID- 11236578
TI  - [Induction of androgenesis in vitro in the spring soft wheat. Balance of
      exogenous and endogenous phytohormones].
AB  - We analyzed the phytohormonal features of the induction of androgenesis in vitro
      in cultured spring soft wheat anthers. It is stressed that switching the program
      of microspore development from the gametophytic to the sporophytic pathway is
      controlled by the balance of exogenous and endogenous phytohormones.

PMID- 11236582
TI  - [Searching for the optimal combinations of regulator anxiolytic peptides:
      theoretical rationale].
AB  - A vector method is proposed to initially select the complexes of regulatory
      peptides (RPs) with certain functional characteristics. As the result of a
      theoretical search for the optimal combinations of anxiolytic RPs with different
      spectra of side effects, the following complexes are proposed for subsequent
      experimental investigation: NPY-ANP, NPY-SP, NPY-NT, NPY-CGRP, NPY-DSIP, NPY-MIF
      1, NPY-SP-MIF-1, NPY-ANP-DSIP, and NPY-CGRP-DSIP.

PMID- 11236581
TI  - [The adrenoreceptor blocker prazosin does not prevent synchronization of the
      protein biosynthesis rhythm by exogenous gangliosides in the hepatocyte culture].
AB  - We studied the effect of the alpha 1-adrenolytic prazosine on dense cultures of
      hepatocytes, which are normally characterized by the protein synthesis rhythm,
      and diluted cultures, in which such a rhythm is revealed after external
      synchronization. Exogenous gangliosides (a fraction of the total gangliosides of
      the bovine brain) then synchronize the rhythm in diluted cultures; this effect is
      also displayed in the presence of 10(-7) M prazosine. The synchronizing effect of
      the medium conditioned by dense cultures was also preserved in the presence of
      prazosine. In the dense cultures that don't normally require external
      synchronization, prazosine affected intensified the rhythmic patter of changes in
      the protein synthesis. After a total of 0.3 microM gangliosides were introduced
      in the medium with prazosine-pretreated dense cultures, the protein synthesis
      rhythm was visualized. We propose that, while blocking adrenoreceptors, prazosine
      does not prevent the action of exogenous synchronizing factors on the
      hepatocytes, but inhibits the release of such factors from the cell.

PMID- 11236583
TI  - [Quantitative evaluation of populations of neurons expressing dopamine synthesis
      enzymes in the arcuate nucleus neurons in developing rats].
AB  - The ratio of neuron populations expressing either tyrosine hydroxylase or
      aromatic L-amino acid decarboxylase, which are enzymes of dopamine synthesis, was
      estimated quantitatively in the arcuate nucleus of male and female rats on 21st
      day of intrauterine development, the 9th day of postnatal development, and in
      adult animals. The enzymes in neurons were revealed by double immunocytochemical
      labeling, followed by identification under a fluorescence microscope. At all the
      developmental stages, three neuron populations differing in the expression of
      these enzymes were revealed. By the end of the prenatal period, most of the
      neurons (99%) contained only one of the enzymes, and the proportion of neurons
      expressing both enzymes (dopaminergic neurons) did not exceed 1%. During
      postnatal development, the proportion of neurons with one enzyme proved to
      decrease, whereas that of dopaminergic neurons increased. However, the latter
      proportion, even in adult animals, did not exceed 50% of the total number of
      neurons expressing the enzymes of dopamine synthesis. Thus, the population of
      neurons expressing both enzymes increases during rat ontogeny, whereas the number
      of neurons expressing only one enzyme decreases.

PMID- 11236584
TI  - [Complex compound of heparin and glutamic acid: synthesis and effect on
      hemostasis parameters in vitro and in vivo].
AB  - A complex compound of high-molecular heparin and glutamic acid has been
      synthesized. This compound has anticoagulant, fibrinolytic, and antithrombotic
      properties in vitro. Single intravenous or chronic peroral introduction of the
      complex in normal animals imitates the activation of anticoagulation system. When
      the anticoagulation system in depressed, the complex restores or even activates
      the anticoagulant-fibrinolytic background of the serum it. The obtained data are
      discussed in physiological terms.

PMID- 11236585
TI  - [Biodiversity in plankton, benthos, and fish communities, and ecosystems of fresh
      water bodies with various productivity].
AB  - The species diversity of phyto- and zooplankton, benthic animals, and
      ichthyofauna was studied in continental water bodies that differ in type,
      geographic location, size, and productivity. The results showed that the number
      of species in the communities of aquatic organisms and in ecosystems depends on
      the area and volume of the water body and the level of plankton primary
      production. Corresponding relationships can be approximated by the equations of
      exponential and polymodal functions. The species number and biomass per unit area
      or volume proved to decrease the area or volume of the water body increased. The
      greatest number of heterotrophic species was observed in water bodies whose
      primary production approached 1400 kcal/m2 per year. It is proposed that the
      number of aquatic species in a body of water depends on the total area of the
      latter and the area of individual territories occupied by the representatives of
      certain species.

PMID- 11236586
TI  - [Photosynthesis and flows of organic carbon, carbon dioxide, and oxygen in the
      ocean].
AB  - The modern concept of photosynthesis as a mechanism for utilizing the energy of
      solar radiation is used as the basis for assessing the scale of photosynthetic
      production of initial organic matter in the ocean (primary biological
      production), its destruction, the carbon and carbon dioxide cycles (flows)
      involved in this process, and the size of oil- and gas-bearing hydrocarbonaceous
      formations originating in sedimentary deposits.

PMID- 11236587
TI  - [Optimal age of sexual maturity and limitations of juvenile survival in mammals].
AB  - Although the life history evolution of small- and large-bodied mammals seems to
      be governed by different factors, the both shows relative neonate size and
      juvenile survival to be slightly dependent on body mass. I propose a hypothesis
      that natural selection simultaneously maximizes a time to maturity (minimizes
      somatic growth rate) and a number of newborn survived to reproduction. In this
      case optimal juvenile survival of large-bodied mammals must be close to e-beta
      and that of small-bodied approximately e-(1 + beta), where beta is the slope of
      the regression of log annual fecundity on log annual juvenile mortality. Analysis
      of vital characters for 71 mammal species revealed the slope to be close to
      unity. As a result frequency distribution of log juvenile survival shows
      bimodality which coincides well with predicted optimal survival for large- and
      small-bodies species. It is shown that the relative neonate size can be directly
      proportional to the juvenile survival and inversely proportional to the lifetime
      offspring production irrespective of mortality factors.

PMID- 11236588
TI  - [Body mass, population density, and offspring number in mammals].
AB  - The negative relationship between population density and body mass with the body
      mass exponent of -0.75 implies that the energy flow through populations of small-
      and large-bodied species is the same, for individual metabolism scales to body
      mass raised to the power of +0.75. This relationship called the energetic
      equivalence rule, has often been observed for mammal species assemblages studied
      at regional scales. Here we suggest a demography-based mechanism that may
      generate it. Having analyzed about 130 literature sources, mostly in Russian, we
      collected demography and body-mass data for 88 mammalian species from the
      territory and coastal waters of the former Soviet Union. The data were used to
      construct a number of interspecific relationships. It is shown that (1) the
      number of offspring per lifetime is approximately inversely proportional to the
      relative mass at birth (the exponent is not significantly different from -1), (2)
      the average lifespan is proportional to body mass to the 0.25 power, (3) body
      mass at birth is proportional to the adult body mass. We develop a simple theory
      to demonstrate that relations (1) to (3) entail the energetic equivalence rule.
      The theory also allows us to explain violation of this rule (in non-flying birds,
      for example), namely, to predict the exponent of relation (1) for any given
      exponent of the relation between population density and body mass. This is
      possible because relations (2) and (3) are likely to more universally hold than
      relation (1). Finally, since natural selection acts on individual traits rather
      than on population-level ones such as population density, the theory opens up the
      way to an evolutionary explanation for the energetic equivalence rule.

PMID- 11236589
TI  - [Comparative embryology of nematodes and the law of embryo similarity].
AB  - Two types of embryonic development can be distinguished within nematodes, with a
      variable (Enoplia) or invariant (remaining species) cleavage. In the case of
      invariant cleavage two main variants of cell lineage are presented in nematodes,
      with the posterior (Rhabditea) or anterior (Dorylaimida) localization of endoderm
      material at the two-cell stage. This classification is in a good agreement with
      some modern nematode taxonomy and it is supported by molecular phylogeny studies.
      The variable cleavage is plesiomorphic. Traditional concept of "mosaic" cleavage
      is not applicable for nematodes as inductive interactions and a regulation of
      experimental interventions are usual attributes of any mode of nematode
      development. The representatives of order Rhabditida have almost identical cell
      lineage, but at the same time they have strong interspecific differences in
      mechanisms of ooplasmic segregation any early inductive interactions. The
      diversity of geometric patterns in the early cleavage, often at the level of
      individual random variations, is a usual characteristic of nematodes including
      species with the invariant cleavage. Thus, the early stages of nematode
      development are evolutionary very flexible, but at the course of embryonic
      development similarity of different species is progressively increased up to the
      uniform morphogenetic stages. The dynamics of variation in nematode development
      contradict to the von Baer's law but are in an agreement with the modern
      "hourglass model" (Doboul, 1994; Raff, 1986).

PMID- 11236590
TI  - [Comparative analysis of topological organization in Metazoa].
AB  - Topological patterns in Metazoa, using previously elaborated methodology with
      employment of the genus of the surface (p) as topological invariant are
      considered. The term "density of the genus of the surface" is introduced. In
      sponges and in a lesser degree among Cnidaria and, Ctenophoria an increase of
      genus p up to indefinite high values and the shaping of topologically complicated
      quasifractal systems (irrigation system in sponges and gastro-vascular system in
      Radiata) are evident. In most Bilateria a stable topological pattern with open
      digestive tube is formed and subsequent topological complications of other
      systems may occur. Complicated topological patterns increasing the genus of the
      surface are evolved on the base of quasifractal systems: gut pockets in
      turbellaria, tracheal system in arthropods, bronchial system in birds, gills in
      bivalve mollusks, etc. Peculiarities of ordered and disordered topological
      patterns as well as topological origin of the increase of the genus of the
      surface are considered.

PMID- 11236591
TI  - [Comparison of imaginal diets of various Syrphidae (Diptera) species].
AB  - The full amount and species composition of pollen from intestines of 11 species
      of Syrphidae (Arctophila fulva, Eristalis arbustorum, E. nemorum, E. pertinax,
      Helophilus pendulus, Myiatropa florea, Rhingia campestris, Sericomyia silentis,
      Syrphus baltheatus, S. ribessii and S. vitripennis), collected at the some place
      (Torma, Jogeva distr., Estonia) and at the some time (18-20 July 1989) have been
      studied. Maximum number of pollen grains is different fly species varied from
      67,800 (Rh. campestris) up to 240,700 (S. silentis) grains, and average number
      from 25,560 (Rh. campestris) up to 115,880 (E. pertinax) grains. Maximum volume
      of pollen in different fly species varied from 1.5 (S. ribesii) up to 23.6 (S.
      baltheatus) mm3, and average volume from 0.36 up to 7.0 mm3 (the same species).
      The difference in a imaginal diets of Syrphidae are found, and the degree of
      difference does not correlate with a degree taxonomic affinity of species. The
      difference in strategy of a feeding behavior of two Syrphus species, that have
      similar diet, are marked: in intestines of 80% specimens of S. ribesii we found
      pollen grains of less that 7 plant species, whereas intestines of more than 88%
      specimens of S. vitripennis contained more than 8 species of grains. Distinction
      in alimentary preferences of different species of files can not be explained
      neither particularities of their morphology, nor their color preferences.

PMID- 11236592
TI  - [Analysis of changes in heart rate and temperature of the ground squirrel
      Citellus undulatus in various physiological states].
AB  - Heart rate (HR) of ground squirrel C. undulatus was studied in dependence of
      season, level of activity, physiological state and air temperature (T). In summer
      HR varies from 110-130 beat/min in sleep up to 420 beat/min at flight from
      danger. During winter hibernation HP was minimal (3-5 beat/min) at T 1-4 degrees
      C, the increase in T induced the growth of HP in correspondence to the Arrenius
      van't Hoff law. The temperature of the body in hibernation exceeded T on 1.5-3
      degrees C. The time of getting off the hibernation increased with the decrease in
      T (6-7 hours at -1 degree C and 2.5-3 hours at +18 degrees C). At phase of
      increased thermogenesis during arousal heart temperature exceeded rectal one on
      10-12 degrees C and heart rate run up to 360-420 beat/min i.e. 2-3 time higher
      than in active state. The decrease in T stimulated the increase in HP up to 3.8
      in winter and 5.3 beat/min/degree C in summer. The highest values of Q10 for HP
      were revealed at the beginning of hibernation (15-20) and at the beginning of
      arousal (6-7), in other periods Q10 was similar to the normal biological values
      (2-2.5). Thus, at the beginning of transitional periods changes of HP were
      determined mainly by endogenic mechanisms that inhibited myocardium at the
      beginning of hibernation and activated in arousal. Some mechanisms of
      coordination between activities of heart and other systems of organism are
      considered. The features of hit exchange providing the hibernation in wide range
      of T are discussed.

PMID- 11236593
TI  - [Vigilance and fearfulness of reindeer: population differences].
AB  - Distances of detection and flight away of reindeer disturbed by approaching human
      on foot were used to compare reindeer alertness and vigilance. Population
      differences depended on genetic origin (wild, feral, and tame reindeer) and
      hunting. No correlations of vigilance and alertness were found with presence of
      predators, sex composition of herds, and presence of newborns in herd. Herd size
      affecting jointly with genetic origin or hunting had negative correlation with
      alertness.

PMID- 11236595
TI  - Get rid of state licensure.

PMID- 11236596
TI  - IT vs. human interaction.

PMID- 11236597
TI  - Genomics matters now.

PMID- 11236598
TI  - E-health and the consumer. Give 'em what they want.

PMID- 11236599
TI  - Finance. Lost in the APCs (ambulatory patient classifications).

PMID- 11236600
TI  - Patient safety. File a plan, or else.

PMID- 11236601
TI  - Arbitration agreements. Less trying.

PMID- 11236602
TI  - Medicaid loophole. States get a break--for now.

PMID- 11236603
TI  - Medication errors. Coping with guilt.

PMID- 11236604
TI  - Cafeteria outsourcing. Send in the chefs.

PMID- 11236606
TI  - Nuts, bolts and brains. It takes a hefty investment, but medical robotics is
      moving from sci-fi to reality.

PMID- 11236605
TI  - HIPAA. Early adopters.

PMID- 11236607
TI  - Washington wish list. Interview by Dagmara Sarudi, Terese Hudson Thrall, Richard
      Haugh, Joyce Kelly.

PMID- 11236608
TI  - Empirical treatment of sepsis in neutropenic patients.
AB  - Mortality associated with febrile neutropenia has dramatically decreased over the
      last three decades; a pivotal role has been played by the concept of hospital
      based empirical therapy with broad-spectrum combinations of antibiotics.
      Nevertheless, there is evidence that a subgroup of patients with febrile
      neutropenia might benefit from less aggressive treatments.

PMID- 11236609
TI  - Understanding screening: requirements for a successful programme.
AB  - Screening has generally been successful in identifying those at risk from
      disease. This success has led to the belief that screening in the general
      population is always a good thing. However, there are pitfalls which must be
      avoided if screening programmes are to achieve what is intended for them.

PMID- 11236610
TI  - A new approach to improving facilities for resident hospital doctors.
AB  - The British Medical Association and the Department of Health recently agreed
      tougher systems to force NHS trusts to improve living conditions for resident
      doctors. Central to the proposals is the system of monitoring pioneered in the
      West Midlands, described below, which has resulted in significant improvements in
      the facilities provided by the region's trusts in the last 3 years.

PMID- 11236611
TI  - How to get your medical book published.
AB  - What do medical publishers want? What types of book sell well? How you should you
      approach a publisher with an idea for a book? This article provides answers to
      these and other questions. Doctors with good ideas for books are in demand. But
      beware, success also carries penalties!

PMID- 11236613
TI  - Who should do thyroid surgery?

PMID- 11236612
TI  - Medical causes of GI symptoms.

PMID- 11236614
TI  - Lipogranulomatous adenopathy: a characteristic but under-recognized presentation
      of Whipple's disease.

PMID- 11236615
TI  - An unusual cause of third nerve palsy.

PMID- 11236616
TI  - Adrenal insufficiency masquerading as an acute abdomen.

PMID- 11236617
TI  - In the public's view.... Quashing the MMR hype: can we overcome the media's
      influence?

PMID- 11236618
TI  - National guideline on induced abortion.

PMID- 11236619
TI  - Managing complaints: part of daily clinical practice.

PMID- 11236620
TI  - The clinical and diagnostic features of mitral valve disease.
AB  - Mitral valve disease remains common, and requires regular clinical and
      echocardiographic review. Surgery is indicated soon after the development of
      symptoms or at the first sign of left ventricular decompensation in mitral
      regurgitation or of the right ventricle in mitral stenosis.

PMID- 11236621
TI  - Current management of hypertrophic cardiomyopathy.
AB  - Hypertrophic cardiomyopathy is a familial cardiac disorder with heterogeneous
      expression and a diversity of morphological, functional and clinical features.
      Some individuals with hypertrophic cardiomyopathy may be asymptomatic while
      others are disabled by symptoms of angina and breathlessness. This article
      summarizes the genetics, pathophysiology and present management of this important
      condition.

PMID- 11236622
TI  - Sexually-acquired reactive arthritis.
AB  - Reactive arthritis is the most frequent cause of acute peripheral arthritis in
      young men. The aetiopathogenesis of reactive arthritis is reviewed, together with
      the varied clinical features. Finally the treatment and prognosis of this
      challenging condition are discussed.

PMID- 11236623
TI  - Cardiac troponin levels in patients with impaired renal function.
AB  - Cardiac troponins are important indicators of myocardial damage. Recent studies
      have shown that serum cardiac troponin levels are raised in at least 50% of
      patients with renal disease. The mechanisms and implications of these findings
      are discussed.

PMID- 11236624
TI  - Permacol: clinical experience with a new biomaterial.
AB  - Permacol (Tissue Science Laboratories plc, Aldershot, Hants) is a new biomaterial
      which combines the strength and permanence of synthetic surgical repair materials
      with the biocompatibility of natural materials. This article examines the
      clinical application of Permacol in a range of different surgical procedures.

PMID- 11236625
TI  - Almotriptan: a balanced approach to migraine.
AB  - Effective acute treatment of migraine is possible with the 4HT(1B/1D) agonists
      (triptans), but their use has been limited in the UK because of concerns about
      limited efficacy, recurrence of attacks, adverse events, and cost.  Almotriptan
      (Almogran, Lundbeck Ltd, Milton Keynes), the most recently available member of
      the class, offers some advantages over previously available agents.

PMID- 11236626
TI  - [New full length cDNA cloned from normal pituitary and pituitary tumors].
AB  - OBJECTIVE: To clone new full length cDNA from normal pituitary and pituitary
      tumors. METHODS: cDNA libraries of human normal pituitary and pituitary tumors
      were constructed, and large-scale sequencing and bioinformatics were used. Silico
      cloning and rapid amplification of cDNA ends (RACE) were also used. RESULTS: 67
      new full length cDNAs were cloned: 41 were cloned from normal pituitary, and 26
      from pituitary tumors. Of the 67 cDNAs, 16 were related with endocrine function;
      at least 2 with a classical signal peptide were secretory protein, and 3 with
      classical transmembrane domains were transmembrane protein. Among the 5 cloned
      new full length cDNAs involved in signal transduction pathway of hormone, at
      least 2 participated in signal transduction pathway of receptors with tyrosine
      kinase activition. CONCLUSION: During short time, 67 new full length cDNA were
      cloned from normal pituitary and pituitary tumors by large-scale producing
      expressed sequence tags. Some of them may play an important role in the
      regulation of physiological and pathological processes of pituitary.

PMID- 11236627
TI  - [Partial nucleotide sequences of hepatitis E viruses isolated from patients in 14
      cities of China].
AB  - OBJECTIVE: To investigate the genotypes of hepatitis E viruses isolated in China.
      METHODS: The partial genome of open reading frame 2 (nt6461-6860, nt5994-6294) of
      45 HEV isolated from patients in 14 cities of China was amplified and sequenced
      using polymerase chain reaction and direct sequencing. RESULTS: 41 of 45 isolates
      (91%) shared the same genotype with HEV Burma strain (B), with nucleotide
      identities higher than 98% with the representative HEV Chinese strain. Only 4 HEV
      isolates were significantly divergent from the 3 prototype strains of HEV, with
      nucleotide identities of 77%-80% with HEV Burmese/Chinese strain, 74%-76% with
      Mexico strain and 74%-77% with the newly discovered HEV US/Swine strain,
      respectively. Phylogenetic analysis suggested that these 4 isolates represented 2
      different subtypes belonging to a novel genotype of HEV, which was significantly
      divergent from the prototype Mexican, Burmese and US/Swine isolates. CONCLUSION:
      Among patients with hepatitis E in China, most are infected with the Chinese
      prototype HEV, and only a small part with the new genotype HEV.

PMID- 11236628
TI  - [Cochlear hypoxia and mtDNA deletion: possible correlated factors to cause
      presbycusis].
AB  - OBJECTIVE: To find the relationship among the most common mitochondrial DNA
      (mtDNA) 4,977 bp deletion, aging and deterioration of acoustic organ and
      determine the pathologic factors causing mtDNA 4,977 bp deletion. METHODS: Sixty
      seven temporal bones from a presbycusis group, an age-matched control group and a
      young control group were evaluated. The nested PCR and tri-nested PCR techniques
      were used to test the presence of mtDNA 4,977 deletion. Computer imaging
      processing was used to measure the parameters of blood vessels in the internal
      acoustic meatus. RESULTS: Temporal bones from patients aged 50 years or over
      frequently showed mtDNA 4,977 deletions. In presbycusis patients, 17 of 34 ears
      showed mtDNA 4,977 deletion, whereas only 4 of 19 ears from the age-matched
      control group showed mtDNA 4,977 deletions. mtDNA 4,977 deletions were often seen
      in the spiral ganglion and vestibular ganglion neurons. In the presbycusis group,
      the lumen of the vasa nervosum of the internal auditory meatus showed a more
      severe reduction in patients with mtDNA 4,977 deletion than in those without
      deletion. CONCLUSION: There is a strong correlation between presbycusis and mtDNA
      4,977 deletion. We hypothesize that cochlear hypoxia may cause mtDNA 4,977
      deletions and other mtDNA mutants which in turn may cause a reduction of
      mitochondrial oxidative phosphorylation and decreased auditory nerve function.
      The symptoms of neural presbycusis, however, may appear only after mtDNA
      metabolism decreases below a specific threshold.

PMID- 11236629
TI  - [Plasma total homocysteine and pulmonary thromboembolism].
AB  - OBJECTIVE: To investigate whether the elevated plasma homocysteine increases the
      risk of pulmonary thromboembolism in the Chinese population. METHODS: Sixty-nine
      patients with pulmonary thromboembolism and 90 sex- and age-matched healthy
      controls were recruited, and the patients were diagnosed using lung
      ventilation/perfusion scan and/or ultrafast CT as well as medical history. The
      concentration of plasma total homocysteine (tHcy) was measured with high
      performance liquid chromatography and environmental factors were collected.
      RESULTS: No significant difference was seen in family history of pulmonary
      thromboembolism and cardiovascular diseases, cigarette smoking, alcoholic
      drinking, oral contraceptive and body mass index between cases and healthy
      controls. The concentration of plasma tHcy in cases was significantly higher than
      that in healthy controls (16.60 mumol/L +/- 1.75 mumol/L vs 12.48 mumol/L +/-
      1.47 mumol/L; t = 3.821, P < 0.05), and adjusting for environmental factors did
      not change the significance. The plasma tHcy in the isolated pulmonary
      thromboembolism patients was lower than that in the patients who had lower limb
      deep venous thrombosis, but no significant difference was found. Compared with
      normal plasma tHcy, hyperhomocysteinemia was associated with a 4.99-fold risk of
      pulmonary thromboembolism. CONCLUSION: Our results show that the elevated plasma
      tHcy increases the risk of pulmonary thromboembolism, and hyperhomocysteinemia is
      an independent risk factor of pulmonary thromboembolism in the Chinese
      population.

PMID- 11236630
TI  - [Genetic analysis of hereditary factor VII deficiency from a Chinese pedigree].
AB  - OBJECTIVE: To identify the mutation in coagulation factor VII gene from a Chinese
      patient with hereditary coagulation factor VII deficiency. METHODS: The genomic
      DNA fragments of FVII gene from a propositus and normal subjects were amplified
      using polymerase chain reaction (PCR), and analyzed with direct sequencing of PCR
      products. The PCR amplified genomic DNA fragments of FVII gene from the
      propositus and her family members were analyzed using restriction enzyme Hgic I.
      RESULTS: The FVII gene sequences of normal subjects were identical to the data
      published, while a missense mutation (TGT-->GGT) was found at codon 329 in FVII
      gene of the propositus. The heterozygous condition for the mutation was revealed
      in her three family members. CONCLUSION: We have found a novel mutation (TGT-
      >GGT) at codon 329 in FVII gene of a patient with hereditary FVII deficiency,
      which leads to a cystein residue replaced by a glysine. PCR combined with
      restriction enzyme Hgic I digestion would be a rapid diagnostic method for this
      mutation.

PMID- 11236631
TI  - [The cloning and expression of soluble HLA-B27 gene].
AB  - OBJECTIVE: To clone and express the soluble HLA-B27 (sB27) gene in human B
      lymphoid cell line. METHODS: Soluble B27 cDNA was constructed by 3 consecutive
      rounds of PCR and then cloned into the RSV5neo vector. The construct was
      transfected into C1R cells. RESULTS: Restriction enzyme digestion and DNA
      sequencing confirmed that the construct was the HLA-B27 gene lacking exon 5 which
      encodes the transmembrane domain of HLA molecule. The expression of aHLA-B27 was
      verified successfully in the culture supernatant of C1R cells. The level of sHLA
      B27 changed with variable culture conditions, such as temperature and
      concentration of fetal calf serum. CONCLUSION: The sHLA-B27 molecules can be
      generated by alternative splicing of HLA-B27 pre-mRNA. Our construct provide a
      useful model for studying the effect of environmental factors such as bacterial
      infections and cytokine stimulation on the expression of soluble HLA-B27
      molecule. It will also provide clues for the role of HLA-B27 molecule in the
      pathogenesis of spondyloarthropathies.

PMID- 11236632
TI  - [Effect of urotensin II on the airway smooth muscle cell proliferation and its
      mechanism].
AB  - OBJECTIVE: To investigate the effect and mechanism of Urotensin II on the airway
      smooth muscle cell proliferation. METHODS: (1) Using 3H-TdR incorporation to
      determine the effect of Urotensin II on the rat airway smooth muscle cells DNA
      synthesis. Different inhibitors were used to study the role of different signal
      transduction pathway such as protein kinase C (PKC), mitogen-activated protein
      kinase (MAPK), Calcineurin (CaN), Calmodulin-dependent protein kinase (CaM-PK)
      and calcium channel in the mitogenic effect of Urotensin II on the airway smooth
      muscle cells. (2) Using Fura-2/AM to measure the effect of Urotensin II on the
      cytosolic free calcium concentration. RESULTS: (1) Urotensin II (10(-10)-10(-6)
      mol/L) increased the airway smooth muscle cell 3H-TdR incorporation in a dose
      dependent manner and Urotensin II 10(-6) mol/L reached the maximal effect. It was
      seven times as high as that of control (P < 0.01). (2) H7, PD98059, and
      nicardipine, inhibitors of PKC, MAPK and calcium channel, significantly inhibited
      Urotensin II (10(-7) mol/L)-stimulated airway smooth muscle cell 3H-TdR
      incorporation, with the inhibitory rate of 29% (P < 0.05), 45% (P < 0.01), and
      28% respectively (P < 0.05). W7, an inhibitor of CaM-PK, had no effect (P >
      0.05). (3) Cyclosporin A (10(-8)-10(-6) mol/L), inhibitor of CaN, an inhibited
      the airway smooth muscle cell 3H-TdR incorporation induced by Urotensin II (10(
      7) mol/L) in a dose-dependent manner, with the inhibitory rate of 76% at 10(-6)
      mol/L (P < 0.01). (4) Urotensin II (10(-6) mol/L) promoted cytosolic free calcium
      concentration increase by 18% (P < 0.01). CONCLUSION: The effect of Urotensin II
      stimulated airway smooth muscle cells DNA synthesis is mediated by Ca2+, PKC,
      MAPK and CaN signal transduction pathway.

PMID- 11236633
TI  - [Research on the relationship between expression of VEGF and high altitude
      pulmonary edema].
AB  - OBJECTIVE: To investigate the relationship between the expression of VEGF and the
      incidence of high altitude pulmonary edema (HAPE) and the mechanism of high
      altitude acclimatization-adaptation. METHODS: Pulmonary artery endothelial cells
      (PAEC) of rat were cultured. The expression of VEGF in PAEC was detected using RT
      PCR and ELISA. Rats were divided randomly into five groups by weight: control,
      acute hypoxia (exposed to a simulated 8,000 m altitude for 4 hours), and three
      intermittent hypoxia groups (exposed to a simulated 3,000 m or 5,000 m altitude
      for 2 weeks, 4 hours a day, then to a simulated 8,000 m altitude for 4 hours).
      VEGF in the lung was detected using immunohis to chemistry and slot
      hybridization, and the changes of pathology in the lung were observed. VEGF in
      the blood plasma of rats, in men who immigrated to high altitude at different
      times, and in those who suffered from high altitude pulmonary edema were measured
      using ELISA. RESULTS: The expression of VEGF in PAEC was increased under hypoxia
      condition (1% O2) (P < 0.01). In the blood plasma and lung of rats during
      hypoxia, levels of VEGF and VEGF mRNA were higher than that in the control group.
      VEGF in acute hypoxia group was increased significantly compared with that in the
      intermittent hypoxia groups. Leakage of fluid in the lung of rats was observed in
      the acute hypoxia group. The longer the rats acclimatized, the lower the level of
      VEGF expressed, and the less the fluid leaked in the lung. The same tendency
      could be seen in humans. The level of VEGF in patients with high altitude
      pulmonary edema pre-therapy was higher than that measured post-therapy.
      CONCLUSIONS: Hypoxia could stimulate the expression of VEGF, and the upregulated
      expression of VEGF is one of the most important factors of incidence of high
      altitude pulmonary edema.

PMID- 11236634
TI  - [Differentiation of embryonic stem cells into neuronal cells in vitro].
AB  - OBJECTIVE: To investigate the probabilities of embryonic stem (ES) cells
      differentiating into neuronal cells in vitro. METHODS: Mouse ES-D3 cells were
      cultured on the ES conditioned media without mLIF (mouse leukemic inhibitory
      factor, mLIF) for 4 days until ES cell aggregations was formed (embryonic bodies,
      EBs). The EBs were dissociated with trypsin and exposed to retinoic acid (RA) for
      another 4 days, and then replated onto adhesive substrate. Immunohistochemistry
      and RT-PCR assay were performed to identify the properties of the differentiated
      cells. RESULTS: The treated cells expressed neuronal proteins such as MAP-2 and
      GFAP. RT-PCR assay further identified that the induced cells expressed
      transcripts for neural associated genes including GABA-gamma subunit receptor,
      brain factor-1 and tyrosine hydroxylase (TH). CONCLUSION: ES cells can be
      successfully induced into neuronal cells expressing multiple properties of
      neurons in vitro, which could provide resourceful materials for neural
      transplantation.

PMID- 11236635
TI  - [Assessment of the effects of dipyridamole and dobutamine on coronary
      microcirculation using myocardial contrast echocardiography].
AB  - OBJECTIVES: To evaluate the effects of dipyridamole and dobutamine on myocardial
      blood flow (MBF) and myocardial blood volume (MBV), and their ability to detect
      non-flow-limiting coronary stenoses with myocardial contrast echocardiography
      (MCE). METHODS: Thirteen closed-chest dogs were studied at 7-10 days after
      placement of ameroid constrictors around proximal coronary arteries and their
      branches. MBF was measured with radiolabeled microspheres and myocardial plateau
      video intensity (VI, which indicates relative MBV) and microbubble velocity
      (beta) were measured with MCE at rest, after dipyridamole (0.56 mg/kg), and
      during peak dobutamine dose (30-40 micrograms.kg-1.min-1). RESULTS: The effects
      of both agents on MBF were similar in abnormal and normal segments. Plateau VI
      increased more and beta increased less with dobutamine than dipyridamole (P <
      0.05), but the plateau VI ratios and beta ratios between abnormal and normal
      segments were almost identical during both drugs (P < NS), resulting in similar
      perfusion defects. Excellent linear relations were found between the plateau VI
      ratio or beta ratio and MBF (derived from radiolabeled microspheres) ratio from
      abnormal and normal beds during dipyridamole and dobutamine. CONCLUSION: Although
      the effect of dipyridamole and dobutamine on MBV is different, they unmask MBF
      reserve to a similar extent. Thus, the quantification of stenosis severity is
      identical using both agents with MCE.

PMID- 11236637
TI  - [Experimental study on an animal model of axonal form Guillain-Barre syndrome].
AB  - OBJECTIVE: To investigate an animal model of axonal form Guillain-Barre syndrome
      (GBS). METHODS: A strain of Campylobacter jejuni (Cj PENO: 19) from stools of a
      patient with axonal form GBS was isolated. After the lypopolysaccharides (LPS)
      were extracted from the strain, they were inoculated into 26 rabbits, 10
      micrograms per week. RESULTS: Three rabbits showed paralysis, with an incidence
      rate of 11.54%. For the three rabbits, LPS was inoculated two, three and three
      times, respectively. Pathological examination showed serious axonal degeneration
      in the sciatic nerve. The electrophysiological features showed motor axon damage.
      CONCLUSION: The results suggested the presence of an axonal form GBS. LPS in Cj
      could play an important role in causing axonal form GBS.

PMID- 11236636
TI  - [Regulatory effect of antisense VEGF121 cDNA transfection on angiogenesis and
      metastasis of human lung giant cell carcinoma].
AB  - OBJECTIVE: To study the regulatory effect of antisense VEGF121 cDNA transfection
      on endogenous VEGF secretion and angiogenesis of human metastatic lung carcinoma
      cell line PG and explore the significance of microvessel density (MVD) in tumor
      growth and metastasis. METHODS: The eukaryotic expression vectors bearing
      antisense VEGF121 cDNA was transfected into PG cells. Human umbilical vein
      endothelial cells (HUVEC) were cultured in conditioned mediums from transfected
      cells, and proliferation was determined by methyl thiazolyl tetrazolium (MTT) and
      3H thymidine incorporation (3H TdR) assays in vitro. Microvessel density (MVD) in
      xenografted tumors in nude mice was analyzed by immunohistochemistry. RESULTS:
      The transfectant of antisense VEGF121 cDNA exhibited a reduction in VEGF
      secretion. HUVEC grown in conditioned medium from the antisense VEGF transfected
      cells exhibited a decrease in capacities of DNA syntheses and cell proliferation.
      MVD of tumor with transfected antisense VEGF gene was significantly lower than
      that in control vector. CONCLUSION: Antisense VEGF gene transfection can inhibit
      vascular endothelial cell proliferation in vitro and tumor angiogenesis in vivo,
      which may explain its inhibitory effects on tumor growth and metastasis.

PMID- 11236638
TI  - Mainstream media misinterpret HCFA's policy on medical errors.

PMID- 11236639
TI  - Compensation monitor. Some primary care salary increases lag behind other health
      care professionals.

PMID- 11236640
TI  - Defined contribution. Physicians, don't hold your breath.

PMID- 11236641
TI  - Billing for alternative services: who gets paid for what, and how?

PMID- 11236642
TI  - Fighting invisible barriers to equitable health care. Interview by Patrick
      Mullen.

PMID- 11236643
TI  - Persistence with drug therapy: a practical approach using administrative claims
      data.

PMID- 11236644
TI  - 'Business to business' is where real action is in Internet health care.

PMID- 11236645
TI  - Helping patients make informed decisions now harder thanks to range of treatment.

PMID- 11236646
TI  - Managed care outlook. Employers more willing to pass benefit costs along.

PMID- 11236647
TI  - Meningococcal disease, African meningitis belt.

PMID- 11236648
TI  - Recommended composition of influenza virus vaccines for use in the 2001-2002
      season.

PMID- 11236649
TI  - Revision of the International Health Regulations. Progress report, February 2001.

PMID- 11236651
TI  - Choice of mouse strains for gene targeting.

PMID- 11236650
TI  - Overview. Gene knockouts.

PMID- 11236652
TI  - Isolation and maintenance of primate embryonic stem cells.

PMID- 11236653
TI  - Isolation, microinjection, and transfer of mouse blastocysts.

PMID- 11236654
TI  - Aggregation chimeras. Combining ES cells, diploid and tetraploid embryos.

PMID- 11236655
TI  - How to study pathologic phenotypes of knockout mice.

PMID- 11236656
TI  - Analysis of hematopoietic phenotypes in knockout mouse models.

PMID- 11236657
TI  - Gene targeting in ES cells.

PMID- 11236658
TI  - Isolation of embryonic fibroblasts and their use in the in vitro characterization
      of gene function.

PMID- 11236659
TI  - Influence of genetic background on knockout mouse phenotypes.

PMID- 11236660
TI  - Lineage allocation during early embryogenesis. Mapping of the neural primordia
      and application to the analysis of mouse mutants.
AB  - The methods outlined in this chapter discuss a range of techniques that have been
      employed for lineage analysis studies of the neural primordia from the onset of
      gastrulation and during neurulation. As the mouse has been extensively mapped,
      lineage analysis during normal morphogenesis is well understood. Attention is now
      focused on the tissue interactions that are essential for gastrulation and
      neurulation to proceed normally. The key to understanding these tissue
      interactions lies in the study of mutant embryos where abnormal development of
      specific tissue types affects the processes of gastrulation and neurulation.
      Lineage analysis and tissue potency experiments on particular mutant embryos will
      provide insight into these essential tissue interactions. As the first step
      toward undertaking such analysis of the neural derivatives, we have outlined the
      mutant strains available and detailed a protocol for the introgression of the
      lacZ transgene onto the mutant background.

PMID- 11236661
TI  - Generation of double-knockout embryonic stem cells.

PMID- 11236662
TI  - In vitro differentiation of embryonic stem cells and analysis of cellular
      phenotypes.

PMID- 11236663
TI  - Embryonic stem cells in the study of hematopoiesis.

PMID- 11236664
TI  - Interferon-inducible ES cell expression systems.

PMID- 11236665
TI  - Transgenic studies in the mouse. Improving the technology towards a conditional
      temporal and spatial approach.

PMID- 11236666
TI  - In vivo libraries of large insert transgenic mice for genetic mapping.

PMID- 11236668
TI  - Positional-candidate cloning of genes from mouse mutants.

PMID- 11236667
TI  - Epigenetic effects on transgene expression.

PMID- 11236669
TI  - Genetically engineered mice. Husbandry and resources.

PMID- 11236670
TI  - Embryo cryopreservation for transgenic mouse lines.

PMID- 11236671
TI  - Manipulating mouse embryonic stem cells.

PMID- 11236672
TI  - Gene targeting in a centralized facility.

PMID- 11236673
TI  - The LoxP/CRE system and genome modification.

PMID- 11236674
TI  - Creation and use of a Cre recombinase transgenic database.

PMID- 11236675
TI  - [Studies on behavioral and electrographic seizures and structural abnormalities
      using magnetic resonance image in chronic epilepsy model in rats--hippocampal
      entorhinal-tempral neocortex neural pathway].
AB  - AIM AND METHODS: Repeated tetanus (60 Hz, 0.4-0.6 mA, 2 s) were delivered into
      the right and the left dorsal hippocampus (HPC), or into the right and the left
      medial temporal neocortex (MTNC) respectively to establish chronic temporal lobe
      epilepsy model in rats. The possible role of the HPC-Entorhinal cortex (EC)-MTNC
      Neocortex neural pathway in epileptogenesis was discussed based on observing the
      abnormalities in behavior and in EEG or depth electrographes and in T2-weighted
      magnetic resonance images (T2-MRI). RESULTS: 1. Occurrence of primary, secondary
      WEDS and kindling effects were higher in the right dorsal HPC experimental group
      than those in other three experimental groups (P < 0.005, P < 0.001). T2-MRI
      signal hyperintensity was remarkable in lateral ventricles close to the HPC (P <
      0.05), but not in the EC or in the MTNC. 2. These T2-MRI intensity increases were
      related to behavioral abnormalities in some MTNC-stimulated rats. 3. Asymmetric
      behavioral abnormalities and T2-MRI changes were observed in the left and the
      right DHPC-stimulated groups. CONCLUSION: HPC may be an "origin" for
      epileptogenesis and EC may play a "gating" role in it.

PMID- 11236676
TI  - [Effects of hypoxic preconditioning on anoxic tolerance and IL-1 beta expression
      in cultured rat hippocampal neurons].
AB  - AIM: To study the effects of hypoxic-preconditioning on anoxia-tolerance and IL-1
      beta expression in cultured rat hippocampal neurons after anoxia. METHODS: 12 day
      cultured hippocampal neurons in control and hypoxic-preconditioning group were
      exposed to anoxic environment(0.9 L/LN2 + 0.1 L/LCO2) for 2, 4, 8 and 12 h. The
      neurons were immunocytochemically stained using the anti-serum against rhIL-1
      beta, The number of survival neurons and the mean optical density (OD) of IL-1
      beta expression were investigated. RESULTS: The morphological changes and IL-1
      beta expression induced by acute anoxia in hypoxic-preconditioning neurons were
      significantly less than those in control. The number of survival neurons was
      higher in the hypoxia-preconditioning group than that in control group after
      acute hypoxia. CONCLUSION: Hypoxia-preconditioning can induce the development of
      anoxia-tolerance in cultured hippocampal neurons. The decreased IL-1 beta in
      hippocampal neurons may be an adaptive reaction to acute anoxia.

PMID- 11236677
TI  - [The study of fatigue-induced mechanism and the effect of branched-China amino
      acids on exercise mice].

PMID- 11236678
TI  - [Effect of hyperbaric oxygen on the expression of proteins Bcl-2 and Bax in the
      gerbil hippocampus CA1 following forebrain ischemia reperfusion].
AB  - AIM: To study the mechanisms of how hyperbaric oxygen treatment (HBOT) reduced
      neuronal apoptosis following forebrain ischemia reperfusion. METHODS: Changes of
      the expression of protein Bcl-2 or Bax were observed in CA1 region of gerbil
      hippocampus following HBOT on ischemia reperfusion 3 days using the method of
      labelled streptavidin biotin (LSAB) immunohistochemistry staining. For this
      purpose gerbils were exposed to the 0.15 MPa and 0.25 MPa HBO 60 min every day
      for 3 successive days. RESULTS: The expression of protein Bcl-2 in hippocampus
      CA1 was significantly increased in HBOT groups (P < 0.01), and changes in 0.25
      MPa groups were greater than those in 0.15 MPa groups (P < 0.01). The expression
      of protein Bax in hippocampus CA1 was not changed significantly in HBOT groups.
      CONCLUSION: HBO can induce the expression of Bcl-2, which is the mechanism of
      neuronal protecting effect of HBOT.

PMID- 11236679
TI  - [The effect of heat stress on activity of phospholipase A2 of rats thalamus and
      striatum].

PMID- 11236680
TI  - [Excitatory amino acid enhance prepro-somatostatin mRNA expression induced by
      altitude hypoxia in the rat hypothalamus].
AB  - AIM AND METHODS: Contents of glutamate (Glu), asparate (Asp) and expression of
      prepro-somatostatin mRNA (PPS-mRNA) in rat hypothalamus were measured by using
      imitated altitude hypoxia rat model, amino acid analyzer and in situ
      hybridization technique. RESULTS: After rats were subjected to altitude hypoxia,
      contents of Glu and Asp in hypothalamus and PPS-mRNA expression in
      periventricular nucleus (PeVN), paraventricular nucleus (PaVN) and arcuate
      nucleus (ArcN) were increased significantly. Ketamine, a NMDA receptor
      antagonist, could decrease the number of PPS-mRNA neurons in rat hypothalamus
      evoked by altitude hypoxia, but had no effect on Glu and Asp contents evoled by
      altitude hypoxia. CONCLUSION: It is suggested that somatostatin maybe paticipate
      in altitude hypoxia reaction, Glu can enhance PPS-mRNA expression through NMDA
      receptor.

PMID- 11236681
TI  - [Effect of stannius corpuscles homogenates of carp on plasma calcium and
      phosphate in mice].

PMID- 11236682
TI  - [Adaptation of diaphragm muscle strip mechanics to chronic electrical stimulation
      and the effect of change in extracellular Ca2+ in rabbit].
AB  - AIM: The mechanical character of diaphragm muscle after chronic electrical
      stimulation(CES) and effect of the extracellular Ca2+ change have not yet been
      explored. We wondered whether there might be great different change and effect on
      muscle mechanics after CES and the extracellular Ca2+ change. METHODS: The twitch
      tension(Pt), time to peak tension(TPT), half-relaxation time(1/2 RT), tetanic
      tension(Po), fatigue index (FI) and fatigue recovery index(FRI) were respectively
      measured in normal group and CES groups; the switch tensions of diaphragm muscle
      strips were observed in the standard Hank's solution and the Hank's with free
      Ca2+. RESULTS: There were more significant decrease in Pt, Po, FI and FRI, more
      significant lengthening in TPT and 1/2 RT in 10 Hz and 20 Hz groups(P < 0.01).
      However, there was completely opposite effect in 50 Hz and 100 Hz groups. There
      were more significant effect on muscle mechanics of contraction and relaxation in
      10 Hz and 20 Hz groups than that in 50 Hz and 100 Hz groups when the
      extracellular Ca2+ changed. CONCLUSION: After CES the significantly frequency
      dependent were presented on mechanical character of diaphragm muscle strips, and
      there were more effect on diaphragm muscle mechanics in 10 Hz and 20 Hz groups
      when the extracellular Ca2+ was changed.

PMID- 11236683
TI  - [Effect of injection of plasmid DNAs into frog skeletal muscle on twitch force
      and tetanic force].

PMID- 11236684
TI  - [The change of vWF in vascular endothelial cells under different stress].
AB  - AIM: To correlate the injury of vascular endothelial cells during various
      pathological conditions with the change of vWF (von Willebrand Factor) in
      different VEC lines. METHODS: Flow cytometer(FCM) were used to defect the
      immunoflourescent stained vWF in pulmonary artery endothelial cells (PAEC) of pig
      and aortic endothelial cells(AEC) of rats. RESULTS: The positive rates of vWF in
      PAEC of pigs is similar with that in AEC of rats under normal condition, but it
      decreased differently after hypoxic or cold injury. It was very interesting that
      the mean fluorescence intensity of positive PAEC or AEC exposed to hypoxia or
      cold elevated significantly compared with those of control. CONCLUSIONS: The
      change of vWF in VEC can be used to evaluate the function of VEC under different
      stress.

PMID- 11236685
TI  - [Modulation and its mechanism of low power laser on gastric acid secretion in
      rat].

PMID- 11236686
TI  - [Protective effects of SMT on myocardial ultrastructure of ischemia reperfusion
      injury in heart of rat].
AB  - AIM: To Investigate the myocardial ultrastructure effects of SMT on the ischemia
      reperfusion injury (IRI) in the rat heart. METHODS: Eighteen Spraqua-Dawley rats
      were randomly divided into three groups: ischemia reperfusion group (IR),
      subjected to 60 min of o-cclusion and 20 min of reperfusion of the anterior
      descending branch of left coronary artery; IR + SMT group (SMT), given the
      selective iNOS inhibitor S-methylisothiourea sulfate (SMT, 5 mg/kg, i.v.) before
      reperfusion; control group (C), didn't occlude coronary artery after exposing
      heart and observed 80 min. Electrocardiogram (ECG) was recorded. Nitrite and
      nitrate content were measured in myocardium and blood serum. The changes of
      myocardial ultrastructure were observed with electron microscope. RESULTS:
      Ischemia reperfusion induced ST segment elevation and T waves inversion or
      tallness in ECG, damaged myocardial ultrastructure, increased nitrite and nitrate
      content in myocardium and blood serum after IR compared with before IR(P < 0.01).
      Administration of SMT improved the changes of ECG and the injury of myocardial
      ultrastructure. Nitrite and nitrate content of myocardium were lower than IR
      group (P < 0.05). The change of nitrite and nitrate level of blood serum in SMT
      group was nearly in C group. CONCLUSION: SMT can prevent myocardium injury from
      reperfusion following ischemia.

PMID- 11236688
TI  - [Study of EEG approximate entrophy in different brain functional states].
AB  - AIM: The approximate entrophy was applied to study EEG in different brain
      functional states. METHODS: EEG were recorded in 40 cases healthy volunteers, who
      are in five functions states (1. resting conscious with eye-close. 2. resting
      conscious with eye-opened. 3. closed eyes and listening pure tone. 4. staring at
      picture. 5. closed eyes and counting numbers). ApEn were calculated in these EEG.
      RESULTS: The ApEn of frontal was the highest and ApEn of occipital was the lowest
      in resting conscious with eye-closed. ApEn in every brain area were higher than
      that in resting conscious with eye-opened. ApEn were changed in different
      physiological functions. Variation of frontal EEG ApEn value were highest.
      CONCLUSIONS: The ApEn may reflect characteristic of EEG non-linear dynamical. It
      is a stable parameter. The dates of its requirement were fewer. It may be a
      useful parameter in studying EEG time series.

PMID- 11236687
TI  - [Effects of chronic stress on the learning and memory ability and hippocampal LTP
      in rats].
AB  - AIM AND METHODS: A chronic stress model in 21 days with multi-stressors was
      applied to question the effects of stress on the learning and memory ability and
      the hippocampal neuronal synaptic plasticity in rats, using the Y maze test and
      LTP electrophysiological recording in vivo. RESULTS: The impairment of spatial
      learning and memory ability and an obvious suppression in LTP in hippocampal
      dentate gyrus was observed in stress group after chronic stress. CONCLUSION: The
      hippocampal synaptic plasticity may be decreased by the chronic stress. And then,
      the learning and memory ability may also be impaired consequently.

PMID- 11236690
TI  - [The strengthening effect of the biofield of seedlings of wheat and other plants
      on human immune system].

PMID- 11236689
TI  - [The studies on protective effects of SM against myocardial hypoxia/reoxygenation
      injury].
AB  - AIM AND METHODS: To assess the myocardial effects of Salvia Miltiorrhiza (SM)
      injection against hypoxia-reoxygenation injury, 31P NMR was used to trace the
      time courses of high energy phosphates (HEP) content and intracellular pH (pHi)
      of the isolated perfused rat hearts under hypoxia (30 min) and subsequent
      reoxygenation (40 min). RESULTS: It was discovered that SM significantly preven
      ted the decrease in the myocardial HEP content during hypoxia, enhanced the
      recovery of myocardial phosphocreatine (PCr), adenosine triphosphate (ATP) and
      the PCr/Pi (inorganic phosphate) ratios during reoxygenation, and lightened the
      decrease of the myocardial pHi value caused by hypoxia. CONCLUSION: SM improves
      the myocardial energy metabolism level during prolonged hypoxia and subsequent
      reoxygenation and protects myocardium against hypoxia/reoxygenation injury. SM
      significantly attenuates acidosis during hypoxia and prevents the appearance of
      very acidic areas of the myocardium after reoxygenation.

PMID- 11236691
TI  - [Analysis on genetic polymorphism of mtDNA in endurance athletes and sedentary
      subjects].
AB  - AIM: To analysis the sequence variation of the origin region (D-loop) of
      mitochondrial DNA (mtDNA) in elite endurance athletes and sedentary subjects in
      order to find the genetic markers related with performance. METHODS: Using a new
      established PCR method by virtue of tracing sample analysis, the restricted
      fragment length polymorphism (RFLP) of D-loop in mtDNA was assessed in 76 elite
      Chinese endurance athletes (EEA), 33 endurance athletes with average-level(GEA)
      and 20 sedentary control(sc). RESULTS: There is a significant difference in
      distribution of the polymorphism in mtDNA D-loop between the EEA and SC(chi 2 =
      33.3, P < 0.01). CONCLUSION: The sequence variation of D-loop region of mtDNA in
      the elite endurance athletes may contribute to the individual difference in
      aerobic performance and trainability.

PMID- 11236692
TI  - [The blocking effects of extracellular Mn2+ on the inward rectifier potassium
      channel (IRK1)].
AB  - AIM AND METHODS: Two-microelectrode voltage clamp (TEV) method was used to study
      the blocking effects of extracellular Mn2+ on the inward rectifier potassium
      channel (IRK1) expressed in the Xenopus oocytes. RESULTS: Mn2+ can concentration
      , time- and vol-tage dependently block IRK1 instantaneous currents (2 ms after
      voltage applied). Mn2+ has almost no effect on the gating property of IRK1. IRK1
      can not permeate Mn2+ because reverse potential did not changed. External Mn2+
      can inhibit IRK1 macroscopic currents more powerfully when external Mn2+
      concentration is lower and external Mn2+ can increases standard chord conductance
      of IRK1. CONCLUSION: External Mn2+ works through surface potential mechanism.
      Ba2+ is considered as one fast open channel blocker of IRK1 and three exponential
      fitting results indicates that external Mn2+ can compete with Ba2+ in the same
      binding site in IRK1 when external Ba2+ concentration is 30 mumol/L. These mean
      two different mechanisms about external Mn2+ blocking exist.

PMID- 11236693
TI  - [Change in plasma platelet alpha-granule membrane protein-140 contents in high
      altitude pulmonary edema].

PMID- 11236694
TI  - [Modulation of epidermal growth factor on the synthesis of pulmonary surfactant
      and its mechanism].
AB  - AIM: To study the effect of EGF at physiological level on PS synthesis on
      cultured lung explants without serum. METHODS: The total phospholipids and major
      phospholipid components in lung tissues were determined. The amount of 3H-choline
      incorporation into PC was measured. RESULTS: 1. 10(-9) mol/L EGF enhanced 3H
      choline incorporation into PC at 8 h and reached the maximum at 16 h. 2. The
      synthesis of total phospholipids, PC and PG increased from lung tissues exposed
      to 10(-9) mol/L EGF, but membrane characteristic phospholipid showed no change.
      3. TP 47, a PTK inhibitor and H7, a PKC inhibitor could block EGF-induced PS
      synthesis. The release of LDH from lung explants could not be changed by EGF, TP
      47 and H7. CONCLUSION: EGF at physiological level could enhance the adult rat PS
      synthesis, and its modulated mechanisms involved PTK and PKC pathways.

PMID- 11236695
TI  - [The regulation of NO on sleep-wakefulness in rats].
AB  - AIM AND METHODS: The effects of an inhibitor of nitric oxide synthase L-NAME and
      a precursor of NO(L-arginine) on sleep-wakefulness in rats were examined.
      RESULTS: 1. The time of waking was increased(P < 0.01) and the time of SWS was
      decreased(P < 0.01) during the first two hours after injection
      intracerebroventricularly(i.c.v.) of L-NAME 1 mg, this effect was showed across
      the 4 h recording period(P < 0.05). The i.c.v. injection of L-NAME 0.2 mg had no
      significant effect. 2. The time of waking was su-ppressed during the third and
      fourth hours after i.c.v. injection of L-arginine 300 micrograms(P < 0.05). At
      the same time the increase of SWS was observed (P < 0.01). 3. There was no change
      on W, SWS, PS when L-NAME 1 mg was given after administration of L-arginine.
      CONCLUSION: The excitatory effect of L-NAME on wakefulness is mediated by
      inhibition of NOS. This effect could be antagonized by L-arginine. It suggests
      that NO is involved in regulation of sleep-wakefulness.

PMID- 11236696
TI  - [Effect of excite amino acid on tolerance exposed to hypoxic].

PMID- 11236697
TI  - [Influences of taurine and micronutrients on nitric oxide synthase expression and
      cGMP content in rat retina].
AB  - AIM: To investigate the influence of taurine and micronutrients on visual signal
      transmission. METHODS: Wistar rats were divided into three groups, that is
      control group, experiment group 1 and experiment group 2, and fed for 3 weeks
      with normal diet, 5 times and 10 times doses of requirements of taurine, vitamin
      A, vitamin B, zinc and selenium, then each treatment group were divided into
      light group and dark adaptation group. After feeding another 3 days in different
      environments with normal diet, all animals were killed and cGMP level and NOS
      expression were analysed in retina and retinogeniculate. RESULTS: The NOS
      expression and cGMP contents of photoreceptor cells, visual cortex and
      retinogeniculate were increased in dark adaptation group compared with light
      group. Nutritional intervention could enhance the NOS staining in dark
      environment, increased the cGMP contents whether light or dark condition.
      CONCLUSION: The distribution, expression and content of NO and cGMP are quite
      different in various light adaptation status. Taurine and micronutrient
      intervention may modurate the visual signal transmission or vision function
      mediated by the changes of NO or cGMP.

PMID- 11236698
TI  - [The vagus nerve coordinates the motion of gallbladder and sphincter of Oddi in
      the interdigestive period in rabbits].
AB  - AIM: To investigate the effect of vagus nerve on coordinating the motion of
      gallbladder (GB) and sphincter of Oddi (SO) in the interdigestive period in
      rabbits. METHODS: Fasted for 15 h-18 h, but allowed to drink water, the rabbib
      were anesthetized with urethane (1.0 mg/kg, i.v.). In order to measure GB
      pressure, a frog bladder filled with normal saline was put into GB and connected
      to a transducer (TP-200T). Myoelectric signals of SO was recorded by a pair of
      copper electrodes. RESULTS: In the interdigestive period, phasic contractions of
      GB (PCGB) and clusters of spike potentials of SO (CSPSO) was 1:1 correlated (Y =
      0.962X + 0.587, r = 0.982, P < 0.01). That is, every PCGB was accompanied by one
      CSPSO. Microinjection of thyrotropin-releasing hormone (TRH, 0.8 nmol, 1
      microliter) or monosodium glutamate (MSG, 2 mumol, 1 microliter) into dorsal
      vagal complex (DVC) enhanced the motility of GB and SO, and the 1:1 temporal
      relation between PCGB and CSPSO still existed. Vagotomy or intravenous injection
      of atropine inhibited the PCGB and the spike potentials of SO, and the 1:1
      correlation between PCGB and CSPSO disappeared. The spike bursts of SO did not
      respond to the artificial rise of gallbladder pressure. CONCLUSION: In the
      interdigestive period in rabbits, gallbladder and SO contract and relax
      rhythmically and simultaneously. This eoordinated motion between GB and SO is
      controlled by DVC via vagus nerve and peripheral M receptors.

PMID- 11236699
TI  - [A study of the effects of L-arginine in pathogenesis of hypoxic pulmonary
      hypertension].
AB  - AIM: To investigate the role of nitric oxide (NO), nitric oxide synthase (NOS)
      and endothelin-1 (ET-1) in the pathogenesis of hypoxic pulmonary hypertension and
      inhibiting effects of L-Arginine. METHODS: 30 rats were divided into 3 groups,
      normal control group (group NC); Hypoxic group (group HP): exposed to 10% O2 8
      h/day, 3 weeks; Hypoxic + L-arginine (group LT): fed L-arginine 200 mg/kg before
      hypoxia. After exposed to hypoxia 21 days, hemodynamics were measured. Lung
      speciments were examined by light and electronic microscopes and morphometric
      analysis. NO, ET-1 levels in lung tissue were measured, the cNOS quantitative in
      the pulmonary endothelium were examined. RESULTS: In HP group, the mean pulmonary
      arterial pressure (m PAP), pulmonary vascular resistance (PVR) the percentage of
      completely muscular coattype medial muscle layer of pulmonary artery in intra
      acine and ET-1 level of HP group increased (P < 0.01), but NO and cNOS level
      decreased (P < 0.01). Examined by electron micrograph, endothelium cells appeared
      swollen, broken and pealed of, basal lamina parted. The changes above in LT group
      reversed partly. But the changes above were still several than that of group NC
      (P < 0.05). CONCLUSION: The structure remodel of pulmonary arteries and
      endothelium lesion in hypoxia cause m PAP, PVP arising, that are correlated with
      the levels of ET-1 increasing and NO, cNOS decreasing. For L-arginine can partly
      supply NO, it may partly reverse the changes of HPH.

PMID- 11236700
TI  - [Changes of catecholamine content in the brain and thymus of rats during antibody
      response].
AB  - AIM: The kinetic changes of catecholamine content in the brain and lymphoid organ
      of rats during the antibody response were investigated in order to know the
      effect of immune condition on the activity of catecholaminergic nerve in central
      and peripheral nervous system. METHODS: Rats were immunized with sheep red blood
      cells (SRBC). During the days 2-7 after immunization, the content of
      noradrenaline (NA), adrenaline (A), dopamine (DA) and homovanilic acid (HVA) in
      the hypothalamus, hippocampus, brainstem and thymus of rats was determined by
      means of the high-performance liquid chromatography with electrochemical
      detection. RESULTS: 1. NA content in the hypothalamus and hippocampus
      significantly increased, but was strikingly decreased in the thymus during the
      antibody response compared with the saline control. 2. The content in the
      hypothalamus, hippocampus and thymus markedly augmented in the period of antibody
      response. 3. DA content in the hypothalamus significantly increased, but in the
      hippocampus, DA content markedly descended after immunization. HVA, DA
      metabolite, dramatically rose in the hypothalamus and hippocampus. 4. There were
      not significant alterations of catecholamine content in the brainstem during the
      antibody response compared with the saline control. CONCLUSION: The antibody
      response may enhance the activity of catecholaminergic nerve in the hypothalamus
      and hippocampus, and may exert different impact on various catecholaminergic
      nerve in the thymus, but does not markedly affect the activity of
      catecholaminergic nerve in the brainstem.

PMID- 11236701
TI  - [The regulating mechanism of anti-fungicides on mouse oocyte development].
AB  - AIM: To study the mechanism of the effect of gonadotropin-induced oocyte
      maturation. METHODS: Mouse oocytes were cultured in HX-medium, and the effects of
      amphotericin B and ketoconazole on resumption of meiosis of mouse oocyte were
      examined. RESULTS: 1. FSH(10-200 IU/L) induced a dose-dependent manner of oocytes
      maturation in CEO. A maximum increase in GVBD was observed with 25-50 IU/L FSH.
      2. Amphotericin tericim B (0.025-2.5 micrograms/L) caused significant increases
      in GVBD in CEO, which mimicked the function of FSH. 3. Ketoconazole (10(-7)-10(
      3) mol/L) inhibited the effect of FSH on resumption of meiosis, but no effect on
      oocyte spontaneous maturation. CONCLUSION: Amphotericin B and ketoconazole are
      able to affect mouse oocyte maturation, and indicates that they have a regulation
      on FSH-induced synthesis of meiosis-activating sterol.

PMID- 11236702
TI  - [Morphometric study on the effects of estrone on bone in vitro].
AB  - AIM: To study the effects of estrone on the bone resorption and bone formation in
      vitro. METHODS: Long bones from 16-day-old female mouse fetuses were cultured in
      BGJb medium for 48 h. The bones were harvested, then bones length and length of
      their diaphyses were measured under stereo microscope. The histomorphormetric
      analyses on midlongitudinal sections of bones were performed. The numbers of
      osteoclasts and hypertrophic chondrocytes were observed under biological
      microscope. RESULTS: Compared with control, there were significant increase in
      bones length and length of their diaphyses after treated with 10(-7) mol/L
      estrone. Under this condition, decreased osteoclasts and increased hypertrophic
      chondrocytes were observed, too. CONCLUSION: Estrone stimulates bone formation
      and inhibites bone resorption in vitro.

PMID- 11236703
TI  - [Effects of glutamine on the release of glutamate in rat hippocampal slices].

PMID- 11236704
TI  - [The study of mechanism by which mild hypothermia reduced delayed neuronal death
      after cerebral ischemia in gerbils].
AB  - AIM: To study the effect of mild hypothermia on delayed neuronal death as well as
      the relationship between hydroxyl radicals generation in hippocampus and the
      change of dopamine and ATP content in striatum following ischemia/reperfusion in
      gerbils. METHODS: The ischemia was induced by occlusion the both carotid common
      arteries for 10 minutes in gerbils. Animals were divided into four groups: sham
      operated group, ischemic group, ischemia/reperfusion group and mild hypothermic
      ischemia/reperfusin group. The numbers of delayed neuronal death were assessed by
      histological examination. OH. outputs in hippocampus and dopamine content in
      striatum were specifically identified and quantitated by high performance liquid
      chromatography (HPLC) coupled with electrochemical detection (ECD). ATP content
      in striatum was also determined by HPLC. RESULTS: Mild hypothermia significantly
      reduced the numbers of damaged neurons in hippocampus CA1 subfield after ischemia
      in gerbils. In MH group, 2,3-DHBA outputs were much less than that in IR group (P
      < 0.01). Dopamine and ATP content in striatum were higher than those in IR group
      (P < 0.01). CONCLUSION: Mild hypothermia could decrease the delayed neuronal
      death in gerbils by reducing hydroxyl radicals production in hippocampus and
      inhibiting dopamine release as well as prompting the recovery of ATP content in
      striatum following ischemia/reperfusion in gerbils.

PMID- 11236705
TI  - [Monitoring dopamine release by fast cyclic voltammetry: an in vivo study].
AB  - AIM AND METHODS: Using fast cyclic voltammetry (FCV) and carbon fibre
      microelectrode (CFMe), we monitored dopamine (DA) release from caudate
      putamen(CPu), nucleus accumbens(Acb) and central amygdaloid nucleus(CAN) of
      normal rats in vivo, in order to find out the suitable parameters to evoke DA
      release of certain area. DA release was evoked by electrical stimulation of
      medial forebrain bundle(MFB) or ventral tegmental area(VTA). RESULTS: DA release
      from CPu, Acb or CAN were different in contents and the characteristics of
      dynamics. CONCLUSION: Different parameters should be used according to the
      different sites of stimulation in order to get the maximal DA release during the
      experiment.

PMID- 11236706
TI  - [Fluorescent mRNA differential display technique].
AB  - AIM: To apply fluorescent mRNA differential display technique. METHODS: Total RNA
      samples were extracted from human monocyte line U937 treated/untreated with IFN
      and LPS, and were used as templates in differential display PCR. The anchored
      primers used were labeled with the fluorescent tag. After running on 5.6%
      denaturing PAGE gel, differentially expressed bands were excised and recovered,
      and finally reamplified. RESULTS: Three tested samples all showed amplified bands
      differed from 300 bp to 2.0 kb, the bands were bright and clear, the background
      was low. Both yes/no changes and upregulated/downregulated happenings were shown
      simultaneously. The reamplification bands were sharp and pure. CONCLUSION: We
      have successfully practiced fluorescent differential display technique in our
      lab. It is a fast, safe and cost-effective method used to sereen unknown
      expressed genes.

PMID- 11236707
TI  - [Research on relationship between the intracellular free calcium and hypoxia
      time].

PMID- 11236708
TI  - Polypharmacy and the issue of nine or more medications.

PMID- 11236709
TI  - Molecular medicine: a primer for clinicians. Part XII: DNA microarrays and their
      application to clinical medicine.
AB  - Previous papers in our Molecular Medicine series have described how the many
      tools of the molecular biologist are being used to develop practical bedside
      applications of modern molecular biology. We have discussed molecular
      diagnostics, gene therapy, and applications in clinical genetics. In this paper
      we discuss DNA microarray technology which provides a genome-wide profile of gene
      expression. We then describe some current and potential clinical applications in
      the disease diagnosis, prognosis and treatment. Particularly exciting is the
      potential of DNA array technology to provide individualized treatment for a wide
      variety of clinical conditions.

PMID- 11236710
TI  - Antimicrobial resistance: steps to reduce the problem with emphasis on antibiotic
      utilization the Rapid City experience.
AB  - In summary, as the SHEA/IDSA Joint Committee on Prevention of Antimicrobial
      Resistance suggested, it should be easier to prevent the acquisition of
      resistance than to respond after the problem is extensive. We have taken that
      approach in the measures undertaken and outlined above. Our lower rates of
      resistant microorganisms are, in part, due to this, but also due to the diligent
      use of antibiotics by the medical staff-largely in avoiding empiric broad
      spectrum antibiotic therapy when not needed. Our formulary is not restrictive but
      new antibiotics are not added unless there is a proven niche. The most
      appropriate and effective antibiotic at our hospital for Streptococcus pneumoniae
      is penicillin, for Streptococcus pyogenes, penicillin, for Staphylococcus aureus,
      nafcillin, for a severe Escherichia Coli infection, gentamicin, and for
      Pseudomonas aeurginosa, gentamicin and ceftazidime. Our efforts are to maintain
      this favorable situation for our patients and clinicians. Additionally, we will
      continue to explore and implement new avenues of prevention, with an emphasis on
      optimal antibiotic utilization, toward the goal of protecting our patients and
      health care workers from resistant bacteria.

PMID- 11236711
TI  - Patterning and lineage specification in the amphibian embryo.
AB  - Xenopus has been widely used to study early embryogenesis because the embryos
      allow for efficient functional assays of gene products by the overexpression of
      RNA. The first asymmetry of the embryo is initiated during oogenesis and is
      manifested by the darkly pigmented animal hemisphere and lightly pigmented
      vegetal hemisphere. Upon fertilization a second asymmetry, the dorsal-ventral
      asymmetry, is established, with the sperm entry site defining the prospective
      ventral region. During the cleavage stage, a vegetal cortical cytoplasm
      (VCC)/beta-catenin signaling pathway is differentially activated on the
      prospective dorsal side of the embryo. The overlapping of the VCC/beta-catenin
      and transforming growth factor beta (TGF-beta) pathways in the dorsal vegetal
      quadrant specifies dorsal-vental axis formation by regulating formation of the
      Spemann organizer, including the anterior endomesoderm. The organizer initiates
      gastrulation to form a triploblastic embryo in which the mesoderm layer is
      located between the ectoderm layer and the endoderm layer. The interplay between
      maternal and zygotic TGF-beta s and the T-box transcription factors in the
      vegetal hemisphere initiates the specification of germ-layer lineages. TGF-beta
      signaling originating from the vegetal region induces mesoderm in the equatorial
      region, and initiates endoderm differentiation directly in the vegetal region.
      The ectoderm develops from the animal region, which does not come into contact
      with the vegetal TGF-beta signals. A large number of the downstream components
      and transcriptional targets of early developmental pathways have been identified
      and characterized. This review gives an overview of recent advances in the
      understanding of the functional roles and interactions of the molecular players
      important for axis determination and germ-layer specification during early
      Xenopus embryogenesis.

PMID- 11236712
TI  - Checkpoint and DNA-repair proteins are associated with the cores of mammalian
      meiotic chromosomes.
AB  - Meiotic checkpoints are manifested through protein complexes capable of detecting
      an abnormality in chromosome metabolism and signaling it to effector molecules
      that subsequently delay or arrest the progression of meiosis. Some checkpoints
      act during the first meiotic prophase to monitor the repair of chromosomal DSBs,
      predominantly by meiotic recombination, or to ensure the correct establishment of
      synapsis and its well-timed dissolution. In mammals, a number of checkpoint and
      repair proteins localize to the meiotic chromosomal cores, sometimes in the
      context of the synaptonemal complex (SC). Here we discuss possible functions of
      these proteins in the accomplishment of meiotic recombination and normal
      progression of the meiotic pathway. Also, we present arguments for a structural
      role of cores and SCs in the assembly of the repair and checkpoint protein
      complexes on the chromosomes.

PMID- 11236713
TI  - Cytoskeletal and Ca2+ regulation of hyphal tip growth and initiation.
AB  - Hyphal tip growth is a complex process involving finely regulated interactions
      between the synthesis and expansion of cell wall and plasma membrane, diverse
      intracellular movements, and turgor regulation. F-actin is a major regulator and
      integrator of these processes. It directly contributes to (a) tip morphogenesis,
      most likely by participation in an apical membrane skeleton that reinforces the
      apical plasma membrane, (b) the transport and exocytosis of vesicles that
      contribute plasma membrane and cell wall material to the hyphal tips, (c) the
      localization of plasma membrane proteins in the tips, and (d) cytoplasmic and
      organelle migration and positioning. The pattern of reorganization of F-actin
      prior to formation of new tips during branch initiation also indicates a critical
      role in early stages of assembly of the tip apparatus. One of the universal
      characteristics of all critically examined tip-growing cells, including fungal
      hyphae, is the obligatory presence of a tip-high gradient of cytoplasmic Ca2+
      that probably regulates both actin and nonactin components of the apparatus, and
      the formation of which may also initiate new tips. This review discusses the
      diversity of evidence behind these concepts.

PMID- 11236714
TI  - Pattern formation during C. elegans vulval induction.
AB  - Studies of C. elegans vulval development provide insights into the process of
      pattern formation during animal development. The invariant pattern of vulval
      precursor cell fates is specified by the integration of at least two signaling
      systems. Recent findings suggest that multiple, partially redundant mechanisms
      are involved in patterning the vulval precursor cells. The inductive signal
      activates the LET-60/RAS signaling pathway and induces the 1 degree fate, whereas
      the lateral signal mediated by LIN-12/Notch is required for specification of the
      2 degrees fate. Several regulatory pathways antagonize the RAS signaling pathway
      and specify the non-vulval 3 degrees fate in the absence of induction. The
      temporal and spatial regulation of VPC competence and production of the inductive
      and the lateral signal are precisely coordinated to ensure the wild-type vulval
      pattern.

PMID- 11236715
TI  - A molecular clock involved in somite segmentation.
AB  - Somites are transient embryonic structures that are formed from the unsegmented
      presomitic mesoderm (PSM) in a highly regulated process called somitogenesis.
      Somite, formation can be considered as the result of several sequential
      processes: generation of a basic metameric pattern, specification of the antero
      posterior identity of each somite, and, finally, formation of the somitic border.
      Evidence for the existence of a molecular clock or oscillator linked to
      somitogenesis has been provided by the discovery of the rhythmic and dynamic
      expression in the PSM of c-hairy1 and lunatic fringe, two genes potentially
      related to the Notch signaling pathway. These oscillating expression patterns
      suggest that an important role of the molecular clock could reside in the
      temporal control of periodic Notch activation, ultimately resulting in the
      regular array of the somites. We discuss both the importance of the Notch
      signaling pathway in the molecular events of somitogenesis and its relationship
      with the molecular clock, and, finally, in that context we review a number of
      other genes known to play a role in somitogenesis.

PMID- 11236716
TI  - Transcriptional programs regulating vascular smooth muscle cell development and
      differentiation.

PMID- 11236717
TI  - Myofibroblasts: molecular crossdressers.
AB  - Myofibroblasts are unique mesenchymal cells with properties inherent to both
      muscle and nonmuscle cells. They are widely distributed in embryos, are essential
      for the formation of functional adult tissues, and are intimately involved in
      tissue homeostasis and wound healing. Cytoskeletal protein expression and
      contractile properties distinguish them from other cell types. Myofibroblasts
      also express skeletal muscle structural and regulatory proteins, including
      sarcomeric myosin heavy chain and MyoD. Despite the presence of such myogenic
      regulatory proteins, these cells do not terminally differentiate into skeletal
      muscle. This article focuses on the interesting biology of myofibroblasts, their
      origin, and the molecular mechanisms that allow these cells to maintain a state
      intermediate between muscle and nonmuscle cells.

PMID- 11236718
TI  - The rise of breastfeeding in the United States.
AB  - What factors influenced the resurgence of breastfeeding in the last decades of
      the twentieth century? This article has considered several explanations.
      Demographic trends, particularly the increased birth rate among black and
      Hispanic women, coupled with the resurgence of breastfeeding in these groups, may
      have contributed to the increase in the breastfeeding rate during the 1990s but
      likely played a minimal role in the earlier, more dramatic increase. The decrease
      in breastfeeding in the earlier part of the twentieth century may be partly
      attributable to increased maternal employment, but the resurgence of
      breastfeeding occurred during the late twentieth century--a period of
      unprecedented influx of new mothers into the workforce. There is no evidence that
      health care practitioners are providing more support for breastfeeding, and most
      international and US policies postdated the resurgence of breastfeeding, although
      they may have influenced the increase in the 1990s. A more plausible explanation
      of the resurgence of breastfeeding in all major segments of society is the
      pervasive influence of the natural-childbirth movement of the 1960s and 1970s,
      with its effects on the standard management of childbirth. Also, the increase in
      breastfeeding among low-income women may be attributable partly to programmatic
      changes in the provision of supplemental food through the WIC program and the
      targeting of breastfeeding-promotion efforts to the specific concerns of these
      women. Although breastfeeding increased at the end of the twentieth century
      relative to earlier decades, the disparity between the recommended rates and
      those achieved by US women is great. Thus, efforts to increase breastfeeding
      initiation and duration should continue, particularly for the groups that are at
      greatest risk for illness, such as minority and low-income infants. This article
      suggests that the strategies likely to have a lasting effect on future
      breastfeeding rates will be social pressures that affect existing barriers to
      breastfeeding. Such pressures may come from health maintenance organizations,
      insurance companies, and the US government, which are likely to increasingly
      recognize the costs of not breastfeeding to their institutions. The provision of
      flexible work hours and paid maternity leave, either by the US government or
      family-friendly workplaces, could increase the ability of employed women to
      optimally feed their infants. As Retsinas noted in an article on the cultural
      context of breastfeeding, "While it is 'known' that breastfeeding is better, our
      society is not structured to facilitate that choice." Efforts to improve
      breastfeeding rates need to make visible the wider cultural context in which
      infant-feeding choices are made and alter components that make it difficult for
      US women to feed their infants optimally.

PMID- 11236719
TI  - Host defense benefits of breastfeeding for the infant. Effect of breastfeeding
      duration and exclusivity.
AB  - Breastfeeding confers lifesaving protection against infectious illness among
      disadvantaged populations. As a result, breastfeeding promotion has an important
      part in child health programs throughout the world. In this article, the evidence
      regarding the host defense benefits of breastfeeding for term infants of normal
      birth weight is reviewed, with an emphasis on recent information from
      industrialized countries regarding how the degree and duration of breastfeeding
      affect infant health.

PMID- 11236720
TI  - Breastfeeding and chronic disease in childhood and adolescence.
AB  - A growing body of research suggests that infant feeding practices influence the
      risk for several chronic diseases of childhood and adolescence. Increased risks
      for type 1 diabetes, celiac disease, some childhood cancers, and inflammatory
      bowel disease have been associated with artificial infant feeding and short-term
      breastfeeding. As genetic susceptibility is understood more completely and gene
      environment interactions are elucidated, evidence to either confirm or refute
      these findings will be forthcoming.

PMID- 11236721
TI  - Anatomy and physiology of lactation.
AB  - Milk secretion is a robust process that proceeds normally in at least 85% of
      women postpartum. Anecdotal evidence suggests that, with assistance in the
      techniques of breastfeeding, at least 97% of women can successfully breastfeed
      their infants. The causes of lack of success in breastfeeding are not well
      understood because, at least in Western societies, when infants fail to thrive on
      the breast, formula substitution is easy. Although this article is not the place
      to discuss possible pathologic mechanisms, breastfeeding failure usually occurs
      at approximately the first week postpartum, and a much better understanding of
      the mechanisms by which milk secretion is initiated during this period may help
      researchers to understand why some women have severe problems with lactation. The
      general understanding of the mechanisms of milk secretion is fairly good, but the
      regulatory mechanisms at the cellular and molecular levels have not been given
      adequate attention and are ripe for future investigation. Other areas that
      require attention are the behavior correlates of breastfeeding and the transfer
      of drugs and toxins into milk. The latter may have a long-term impact on infant
      health and should receive increased attention.

PMID- 11236722
TI  - Effects of breastfeeding on the mother.
AB  - In the rush to find nutrient alternatives to breastfeeding, a theme that
      dominated research on infant feeding throughout the twentieth century, only
      recently have new findings that reconfirm the importance of breastfeeding for
      maternal and child health begun to influence medical texts and health policy.
      Approximately 30 years of increasingly rigorous and positive research findings
      have led to the rediscovery of breastfeeding as a valid and evidence-based health
      intervention for infants. Unfortunately, because much of the research was
      designed to assess human milk as a nutrient replacement for infant formula, the
      literature on the effects of breastfeeding on maternal health remain limited.
      Nonetheless, a clear pattern of positive physiologic changes that lead to
      improved short-term and long-term health sequelae are emerging. All patients and
      their families should be informed fully as to the positive preventive health
      effects of breastfeeding not only for infants but also for mothers. Women have
      many difficult choices to make; it behooves physicians to ensure that they
      receive all of the facts on which to base these decisions.

PMID- 11236723
TI  - Breastfeeding and brain development.
AB  - Although biochemical evidence seems to support the fact that more DHA is
      incorporated into the brain of breastfed infants compared with formula-fed
      infants, whether the levels of DHA in the brain are clinically significant is
      unclear. Because randomized trials cannot be done, this issue is difficult to
      study. The effects of breastfeeding on developmental outcome in term infants
      seems to be small or insignificant. For otherwise healthy children the potential
      differences are not clinically relevant; however, these small differences
      distributed over an entire population might have a significant effect on society.
      Although significant methodologic concerns exist, the effects of breastfeeding on
      preterm infants may be greater than those for term infants. Extremely low birth
      weight, premature infants (< 750-1000 g) have been found to have IQs that are 13
      points lower than term controls and a 50% to 60% risk for requiring special
      education services when they are in school. In these infants, small improvements
      in IQ and neurologic function could have a much greater effect. Further study of
      neurodevelopmental outcome in premature infants fed breast milk compared with
      those fed preterm formula are indicated. This information should not change the
      practice of encouraging breastfeeding of term and preterm infants because other
      advantages to breastfeeding exist.

PMID- 11236724
TI  - The role of polyunsaturated fatty acids in term and preterm infants and
      breastfeeding mothers.
AB  - DHA and AA, which are components of breast milk but not infant formulas marketed
      in the United States and some other countries, are important components of the
      brain, and DHA is a major component of the retina. Also, many studies have
      demonstrated advantages of breastfeeding versus formula-feeding on subsequent
      cognitive and visual function; however, available data are insufficient to
      justify the conclusion that the presence of DHA and AA in breast milk is
      partially or soley responsible for the apparent advantages of breastfeeding. On
      the other hand, many studies of DHA (and AA)-supplemented versus unsupplemented
      formulas have shown clear advantages of the supplemented formulas on visual
      acuity at 2 and 4 months of age or neurodevelopmental status at 12 to 18 months
      of age. Although one logically may assume that these early effects may have long
      term effects, this assumption is not warranted by the available data. One of the
      major problems is the difficulty of assessing visual and cognitive function of
      infants. Scores on standard neurodevelopmental tests at 1 year of age, for
      example, are only weakly correlated with performance at school age (when more
      definitive assessments are possible), and little is known about the
      predictability of later visual function from behavioral or electrophysiologic
      assessments of visual function early in life. Even prematurely born infants can
      synthesize DHA and AA and other omega-3 and omega-6 LC-PUFAs from the dietary
      EFAs, LA and ALA. Nonetheless, plasma, erythrocyte and brain lipid levels of DHA
      are lower in infants whose diets do not contain DHA. Whether more optimal intakes
      of ALA result in higher plasma and tissue levels of this FA is unclear. The
      breast-milk content of LC-PUFAs is not regulated by the mammary gland but,
      rather, reflects the concentrations of LC-PUFAs in maternal plasma lipids that,
      in turn, are dependent on maternal diet and, probably, maternal activities of the
      desaturases and elongases involved in converting dietary LA and ALA to LC-PUFAs.
      This occurrence suggests that some infants receive sufficient LC-PUFA to support
      normal rates of deposition, whereas others may not. Also, some infants probably
      can synthesize additional LC-PUFAs from the LA and ALA contents of human milk.
      Thus, depending on maternal diet and maternal and infant desaturase and elongase
      activities, some breastfed infants may receive less than adequate LC-PUFAs to
      support normal rates of deposition. Clearly, the role of LC-PUFAs in infant
      development is not a simple issue. Also, no foolproof method exists to ensure an
      adequate but not excessive intake. Thus, because some evidence shows that dietary
      LC-PUFA (DHA, AA, or both) as components of breast milk or formula confers at
      least transient developmental benefits, supplementation of infant formulas with
      LC-PUFAs is supportable provided that the supplements used are safe. The safety
      of all available supplements is unknown; however, some trials reveal few reasons
      for major concerns about the safety of single-cell oils, low-EPA fish oil, or egg
      yolk phospholipid or triglyceride fractions.

PMID- 11236725
TI  - The role of breastfeeding in obesity.
AB  - Most studies examining the effects of breastfeeding on later obesity have found
      an insignificant effect. Breastfeeding was positively associated with later body
      fatness in two studies. A protective effect of breastfeeding on childhood obesity
      was seen in four studies. An effect of breastfeeding on later obesity, if any, is
      probably weaker than genetic and other environmental factors. Also, an observed
      association between breastfeeding and later obesity does not prove causality.
      Controlling for confounders in an attempt to minimize the effects of differences
      between breastfeeding and formula-feeding mothers was done to a varying extent
      across studies. In several of the later studies, adjustment for confounders
      obliterated the effect of breastfeeding. Whether all the pertinent confounding
      factors have been measured and whether the differences between mothers who chose
      to breastfeed and mothers who chose to formula-feed have been controlled for
      adequately are always questionable. The dose response observed with the duration
      of breastfeeding is consistent with a causal association, but confounders
      associated with breastfeeding also may covary in a graded response. Although a
      highly provocative concept, the protective effect of breastfeeding on later
      obesity remains controversial.

PMID- 11236726
TI  - Breastfeeding beyond 12 months. An historical perspective.
AB  - A decade ago, child psychiatrist Coello-Novello, in her term as Surgeon General
      of the United States, said, "It's the lucky baby, I feel, who continues to nurse
      until he's two." The accumulated evidence supports her statement. The
      understanding of the benefits of breastfeeding beyond 12 months should support
      the cultural change in which eventually prolonged breastfeeding becomes normal.

PMID- 11236727
TI  - The use of human milk for premature infants.
AB  - Various methods have been reported and used clinically to augment the nutrient
      supply for human milk-fed premature infants. These methods include specialized
      maltinutrient powdered mixtures (fortifiers), complete liquid formulas designed
      to be mixed with human milk, complete powdered formulas to be mixed with human
      milk, and alternate feeding of human milk and preterm formula. Although the
      optimum nutrition of premature infants is unknown, data are accumulating to
      suggest that human milk, fortified with additional nutrients, is appropriate for
      tube-fed infants. The use of fortified human milk typically provides premature
      infants adequate growth, nutrient retention, and biochemical indices of
      nutritional status when fed at approximately 180 mL/kg/d compared with
      unfortified human milk. Data are needed to determine the precise quantity of
      nutrients to be added as supplements. Nutrient interactions have not been
      explored in detail. Although large quantities of calcium seem to be needed, the
      exogenous calcium may affect fat absorption adversely. Manipulation of milk may
      affect the intrinsic host-defense properties of the milk. Compared with preterm
      formula, the feeding of fortified human milk may provide significant protection
      from infection and NEC. Lastly, the potential stimulation of an enteromammary
      pathway through skin-to-skin contact provides species-specific antimicrobial
      protection for premature infants. Several of these areas require additional
      exploration. Thus, for premature infants, neonatal centers should encourage the
      feeding of fortified human milk, together with skin-to-skin contact, as
      reasonable methods to enhance milk production while potentially facilitating the
      development of an enteromammary response.

PMID- 11236728
TI  - Effects of stress on lactation.

PMID- 11236729
TI  - Given the benefits of breastfeeding, what contraindications exist?
AB  - Breastfeeding is not contraindicated in association with environmental hazards in
      the United States under ordinary circumstances. Unusual massive exposure should
      be assessed on an individual basis. In the face of any possible contraindication
      to breastfeeding, the tremendous benefits of being breastfed should be compared
      with the theoretic risk for the hazard involved and a decision made on an
      individual basis.

PMID- 11236730
TI  - The economic impact of breastfeeding.
AB  - Although breastfeeding is well accepted as the optimal method of infant feeding,
      the US failed to reach the goals set for the year 2000. Support from employers,
      health insurers, health providers, and society are required to reach the goals
      set forth in Healthy People 2010-75% of mothers initiate breastfeeding, 50% of
      infants still receive breast milk at 6 months, and 25% of infants are still
      breastfed at 1 year of age. In today's era of cost accountability and economic
      competition, these groups likely will desire information regarding the financial
      effects of breastfeeding and breastfeeding promotion from their perspectives.
      Although much research still is needed in this area, evidence suggests that a
      significant return on investment is likely with breastfeeding promotion. Also,
      the finances of health care must be viewed within the concept of value. In health
      care, value can be thought of as the cost required to achieve a specified
      outcome. In lay terms, this can be thought of as "how much bang we get for our
      buck." Breastfeeding clearly improves the health of infants and mothers and seems
      to result in cost savings for parents, insurers, employers, and society, which
      means that the medical and economic value of breastfeeding is high. To reap the
      health and economic benefits associated with breastfeeding, society must support
      breastfeeding promotion, which most likely will necessitate a coordinated US
      breastfeeding program. The US government is in a unique position to accomplish
      this goal as it views the associated costs from the joint perspectives of
      employer, health insurer, medical provider, and society. Through support of such
      a program, the US government likely will benefit significantly by improving the
      health of children and its financial bottom line.

PMID- 11236731
TI  - Representative values for constituents of human milk.

PMID- 11236732
TI  - Lactogenesis. The transition from pregnancy to lactation.
AB  - The most important factors in initiation of the cascade of changes in the mammary
      epithelium that constitute lactogenesis stage II seem to be a prepared mammary
      epithelium, progesterone withdrawal, maintained plasma prolactin (in most
      species), and removal of milk from the breast within an undefined interval after
      birth. Although the molecular mechanisms by which prolactin regulates milk
      protein synthesis are the subject of intense and productive studies, the specific
      mechanisms by which progesterone and milk removal interact with the mammary
      epithelial cell at parturition have not been studied, perhaps because no in vitro
      model system exists that mimics lactogenesis stage II, or because of the
      complexity of the changes that must be coordinated during this process, or
      because of a lack of general understanding of the complex progression of changes
      in the function of the breast as it goes from the quiescent state of pregnancy to
      the active secretory state of lactation. With new technologies designed to
      investigate the biology of complex systems arising from the growing knowledge of
      the genome of human and animal species and the growing availability of animal and
      tissue culture models for these processes, physicians can expect a rapid increase
      in the molecular understanding of lactogenesis in the near future. These
      fundamental studies must be coupled with good prospective clinical studies if
      physicians are to obtain a useful, comprehensive understanding of lactogenesis in
      women.

PMID- 11236733
TI  - Nutrient composition of human milk.
AB  - A complex interplay of maternal homeostatic mechanisms influences nutrient
      transfer to nursing infants, and with a few exceptions, excess maternal intake or
      a moderate deficiency in the maternal diet does not appreciably alter nutrient
      transfer to infants unless it has persisted for some time. Milk vitamins D and K
      contents, even in apparently well-nourished women, may not always provide
      adequate amounts for infants. Investigations provide evidence that human milk
      possesses many unique characteristics and that maternal and environmental
      influences are stronger than previously recognized and appreciated. A complete
      body of knowledge does not exist to serve as a basis for dietary recommendations
      to ensure optimal nutrition for mothers and infants. The success of lactation
      usually is measured in terms of infant performance, and cost and consequence to
      the mother are seldom considered. Human milk feeding is recommended for the
      entire first year of life, but few studies focus on the nursing dyad for more
      than 3 months' duration. Continued study is needed so that nutritional adequacy
      may be maintained and appropriate dietary guidance can be provided. When human
      milk feeding is not practiced, modern and reliable data on human milk
      constituents and their significance to infants also are essential for the
      preparation of formulas, especially those not based on bovine milk. The adequacy
      of human milk substitutes cannot be predicted from compositional analysis because
      of possible differences in compartmentalization and molecular form of nutrients,
      and such preparations must be evaluated using specific indices of nutrient use,
      together with traditional anthropometric measures in infants.

PMID- 11236734
TI  - Bioactive factors in human milk.
AB  - This article reviews the bioactive components of human milk. Special emphasis is
      given to immune and nonimmune protective function of major and minor nutrients in
      human milk. Immune modulating components, such as cytokines, nucleotides,
      hormones, and growth factors, are discussed. Milk enzymes with digestive function
      in the newborn are reviewed.

PMID- 11236736
TI  - Breastfeeding lessons from the past century.

PMID- 11236735
TI  - Nutrition, growth, and complementary feeding of the breastfed infant.
AB  - Although additional research is needed on many of the issues discussed herein,
      the following conclusions are well substantiated by the evidence available to
      date: Breast milk alone can meet nutrient needs during the first 6 months, with
      the possible exception of vitamin D in certain populations and iron in infants of
      relatively low birth weight. Complementary foods offered before 6 months of age
      tend to displace breast milk and do not confer any growth advantage over
      exclusive breastfeeding. Breast milk continues to provide substantial amounts of
      key nutrients well beyond the first year of life, especially protein, fat, and
      most vitamins. Breastfed infants tend to gain less weight and usually are leaner
      than are formula-fed infants in the second half of infancy. This difference does
      not seem to be the result of nutritional deficits but rather infant self
      regulation of energy intake. New growth charts based on infants breastfed
      throughout the first year of life are being developed by WHO. The nutrients most
      likely to be limiting in the diets of breastfed infants are minerals, such as
      iron, zinc, and calcium. Using the following guidelines can help to ensure that
      the nutrient needs of the breastfed child are met: Continue to breastfeed as
      often as the infant desires. Aim for a variety of complementary foods, with
      fruits, vegetables, and animal products (e.g., meat, fish, poultry, or egg)
      offered daily. Iron-fortified cereals and meats can provide adequate iron.
      Calcium can be obtained from cheese, yogurt, and other dairy products (although
      fresh cow's milk is not recommended before 12 mo). Avoid giving too much juice.
      Be alert to any signs that the child's appetite, growth, or development is
      impaired. When in doubt, a balanced vitamin-mineral supplement is advisable. Make
      mealtimes enjoyable.

PMID- 11236737
TI  - [Transfer of T-DNA from agrobacteria into plant cells through cell walls and
      membranes].
AB  - Discusses probable routes of agrobacterial penetration through the plant
      integumental tissues, cell wall, and plant cell plasmodesma. Analyzes the
      contribution of extracellular structures of agrobacteria in penetration through
      barriers of a plant cell, primary contact (adhesion), and during DNA transfer
      from bacterial (E. coli, A. tumefaciens) to recipient (bacterial or plant) cells.
      Discusses the relationship between donor cell adhesion to recipient cell surface
      and the infectious and conjugation processes. Considers the probable role of
      piles in conjugative transfer of agrobacterial DNA through membranes of donor and
      recipient (bacterial and plant) cells. Analyzes the contribution of the plant
      cell cytoskeleton to T-DNA transfer. Suggests a model of transport of T-DNA-VirD2
      complex and VirE2 proteins through independent channels consisting of vir-coded
      proteins.

PMID- 11236738
TI  - [A method of genotyping clinical isolates of Ureaplasma urealyticum biovar
      Parvo].
AB  - A new method for typing clinical isolates of U. urealyticum (Parvo biovar) is
      based on SSCP analysis of amplicons of mba gene 5' region and upstream region.
      The mba gene is coding for MB gene of U. urealyticum. This method allows
      genotyping of U. urealyticum isolates using vaginal and cervical swabs without
      culturing. Sixty-two clinical specimens from patients with a history of chronic
      cystitis, chronic pyelonephritis, chronic salpingo-oophoritis, erosion of the
      cervix uteri, and spontaneous abortions were tested for U. urealyticum. The
      bacterium was detected in 64% (40 specimens), 83% (33) of which belonged to Parvo
      biovar. Parvo biovar isolates were analyzed and genotyped as follows: first
      genotype 52%, second genotype 33%, and third genotype 16%. Further sequencing of
      the first and second genotype amplicons showed that the first genotype belonged
      to serotype 3 and second genotype to serotype 6.

PMID- 11236739
TI  - [Structural organization and mechanisms of mobility of the gene cassette coding
      for resistance to antibiotics and bacterial virulence factors].
AB  - The review is focussed on two types of gene cassettes which are significant in
      bacterial variability. The first type are cassettes with antibiotic resistance
      genes; these are the smallest mobile genetic elements including a gene (most
      commonly an antibiotic resistance gene) and a short sequence acting as a
      recombination site. Sometimes these cassettes contain genes not responsible for
      antibiotic resistance but their functions are not yet known. The second type
      contains large clusters of genes coding for bacterial virulence factors. They
      were termed "pathogenicity islands" due to their difference in the percentage of
      G-C pairs in comparison with bacterial chromosomes, in which they are contained.
      The structural organization and mechanisms of mobility of various types of gene
      cassettes are discussed.

PMID- 11236740
TI  - [A new thermostable proteinase from Thermoactinomyces SP.27a. Cloning and gene
      expression].
AB  - A library of Thermoactinomyces sp. 27a, producer of thermostable proteases of
      different groups, has been created. Gene coding for thermostable neutral
      proteinase was cloned and expressed in Bac. subtilis cells. Restriction map for
      cloned DNA fragment was created and physicochemical parameters of recombinant
      proteinase were characterized. The thermostability and optimum of proteolytic
      activity of the enzyme was lower than in the natural Thermoactinomyces sp.
      strain, which can be due to heterologous expression of the gene coding for
      thermostable protein in the mesophilic host.

PMID- 11236742
TI  - Recent Advances in Adipose Tissue Biology and their Implications for Obesity.
      Proceedings of a symposium. Quebec City, Quebec, Canada. November 19-20, 1999.

PMID- 11236741
TI  - [Analysis of the primary structure of hantavirus RNA, detected in organs of
      patients that died from HFKS in the Republic of Bashkortostan].
AB  - Fragments of the minor S and middle M segments of Hantavirus genome RNA were
      isolated by reverse transcription-polymerase chain reaction (RT-PCR) from the
      organs of patients who died from hemorrhagic fever with the renal syndrome (HFRS)
      during an epidemic outbreak of this infection in the Bashkortostan Republic in
      1997-1998. The sizes of the resultant PCR fragments were 317 p. n. for S segment
      and 416 p. n. for M segment. Their primary structures (GENBANK registration
      numbers AJ133581 and AJ133582) were determined and they were compared with the
      nucleotide sequences of the respective genome sites of Hantavirus strain
      CG1820/Ufa-83 isolated from Clethrionomys in Bashkortostan in 1983. The
      homologies of nucleotide sequences of the corresponding sites of S and M segments
      of RNA isolate of 1997 and CG1820/Ufa-83 were 87.7 and 96.6%, respectively. The
      authors discuss the probability of circulation of hantaviruses differing by
      individual features of primary structure of genome RNA in Bashkortostan.

PMID- 11236743
TI  - 12th International Contact Dermatitis Symposium and 1st International Symposium
      on the Prevention of Occupational Skin Disease in Hairdressers. San Francisco,
      California, USA. October 14-18, 1999. Abstracts.

PMID- 11236744
TI  - Immune tolerance in hemophilia and the treatment of hemophiliacs with an
      inhibitor. Proceedings of a meeting. Palermo, Italy, October 1999.

PMID- 11236745
TI  - New medical schools and nuclear medicine in Africa: prestige or necessity?

PMID- 11236747
TI  - Meeting of the American College of Allergy, Asthma, and Immunology. Seattle,
      Washington, USA. 3-8 November 2000. Abstracts.

PMID- 11236746
TI  - Betablockers in the New Millennium. Hamburg meeting, April 1, 2000. Proceedings.

PMID- 11236748
TI  - From the Centers for Disease Control and Prevention. Pseudomonas
      dermatitis/folliculitis associated with pools and hot tubs--Colorado and Maine,
      1999-2000.

PMID- 11236749
TI  - From the Centers for Disease Control and Prevention. Human rabies--California,
      Georgia, Minnesota, New York and Wisconsin, 2000.

PMID- 11236750
TI  - From the Centers for Disease Control and Prevention. Human rabies--Quebec,
      Canada, 2000.

PMID- 11236751
TI  - From the Centers for Disease Control and Prevention. Progress toward
      poliomyelitis eradication--Eastern Mediterranean Region, 1999-September 2000.

PMID- 11236752
TI  - JAMA patient page. Screening for breast cancer.

PMID- 11236753
TI  - From the Centers for Disease Control and Prevention. Multistate outbreak of
      listeriosis--United States, 2000.

PMID- 11236754
TI  - From the Centers for Disease Control and Prevention. Blood lead levels in young
      children--United States and selected states, 1996-1999.

PMID- 11236755
TI  - From the Centers for Disease Control and Prevention. Respiratory syncytial virus
      activity--United States, 1999-2000 season.

PMID- 11236756
TI  - JAMA patient page. Preventing dehydration from diarrhea.

PMID- 11236757
TI  - Abstracts of the oral presentations at the 17th Spring Scientific Meeting of the
      Association of Cardiothoracic Anaesthetists. 14 April 2000, Cambridge, United
      Kingdom.

PMID- 11236758
TI  - Advances in End-Stage Renal Diseases 2001. Proceedings of the International
      Conference on Dialysis, III. January 18-19, 2001. Miami Beach, Florida, USA.

PMID- 11236759
TI  - A messy necessary end: Health care proxies need our support.
AB  - OBJECTIVE: To promote development of written advance directives and appointment
      of a proxy for health care by patients who are under the care of a neurologist.
      BACKGROUND: since 1989, the American Academy of Neurology (AAN) has endorsed but
      not actively promoted advance directives. In the years since publication of the
      Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment
      (SUPPORT), much published material has contradicted the notion that creating
      advance directives offers patients a useful means of extending their autonomy.
      METHODS: The author reviewed the post-SUPPORT literature, in which numerous
      articles criticize and others continue to uphold the use of advance directives.
      He also conducted a pilot study concerning the health care proxy. Additionally,
      he reexamined his experiences as an ethics consultant, mindful of the medical
      literature unfavorable to advance directives, to challenge his own opinion that
      creating directives and appointing a health care proxy are valuable activities
      for all adults to engage in and for neurologists to promote. RESULTS: Very few
      articles focus on advance directives and neurology. This literature is not
      present in neurology specialty journals. Only two of the five neurologists
      approached by the author were positive about advance directives and collaborated
      fully in the pilot study. Reviewing his experiences provided the author with
      numerous examples of the actual or potential usefulness of health care proxies.
      CONCLUSIONS: Increasing the advance directives literature in neurology specialty
      journals may lead to the creation of health care documents by more neurologic
      patients and the development of innovative ways of extending the autonomy of
      previously competent individuals. The author has recently formed a volunteer
      organization, Patient Advocates to Preserve Autonomy (PAPA), to increase
      effectiveness of advance directives. It is hoped that the reservations of some
      neurologists about advance directives and proxy decision-making may be lessened
      if they improve their knowledge of the subject and convince themselves that
      addressing it is one of the obligations attendant on providing "principal care"
      for many of their patients. The focus initially needs to be on attitudes, rather
      than methods. However, this pilot project showed that a passive approach is
      ineffective. A campaign within the AAN to promote advance directives as an aspect
      of principal care would be helpful. Patients who have lost the capacity to make
      their own health care decisions often benefit from advance directives and,
      especially, from having an appointed health care proxy. Those benefits may
      improve if patient, proxy, and physician are carefully prepared for their roles.

PMID- 11236760
TI  - Voluntary Initiative Program II.

PMID- 11236761
TI  - From the Centers for Disease Control and Prevention. Nosocomial poisoning
      associated with emergency department treatment of organophosphate toxicity-
      Georgia, 2000.

PMID- 11236763
TI  - From the Centers for Disease Control and Prevention. Progress in development of
      immunization registries--United States, 2000.

PMID- 11236762
TI  - From the Centers for Disease Control and Prevention. Certification of
      poliomyelitis eradication--Western Pacific Region, October 2000.

PMID- 11236764
TI  - From the Centers for Disease Control and Prevention. Houseboat-associated carbon
      monoxide poisonings on Lake Powell--Arizona and Utah, 2000.

PMID- 11236765
TI  - From the Centers for Disease Control and Prevention. Public Health Service
      recommendations for the use of vaccines manufactured with bovine-derived
      materials.

PMID- 11236767
TI  - The nursing shortage is everyone's problem.

PMID- 11236766
TI  - JAMA patient page. Participating in medical research studies.

PMID- 11236768
TI  - From the Centers for Disease Control and Prevention. Influenza activity--United
      States, 2000-01 season.

PMID- 11236769
TI  - From the Centers for Disease Control and Prevention. Serosurveys for West Nile
      virus infection--New York and Connecticut counties, 2000.

PMID- 11236770
TI  - From the Centers for Disease Control and Prevention. Update: outbreak of acute
      febrile illness among athletes participating in Eco-Challenge-Sabah 2000--Borneo,
      Malaysia, 2000.

PMID- 11236771
TI  - From the Centers for Disease Control and Prevention. Availability and use of
      parenteral quinidine gluconate for severe or complicated malaria.

PMID- 11236772
TI  - JAMA patient page. Pulmonary embolism.

PMID- 11236773
TI  - Efficacy and safety of recombinant human activated protein C for severe sepsis.
AB  - BACKGROUND: Drotrecogin alfa (activated), or recombinant human activated protein
      C, has antithrombotic, antiinflammatory, and profibrinolytic properties. In a
      previous study, drotrecogin alfa activated produced dose-dependent reductions in
      the levels of markers of coagulation and inflammation in patients with severe
      sepsis. In this phase 3 trial, we assessed whether treatment with drotrecogin
      alfa activated reduced the rate of death from any cause among patients with
      severe sepsis. METHODS: We conducted a randomized, double-blind, placebo
      controlled, multicenter trial. Patients with systemic inflammation and organ
      failure due to acute infection were enrolled and assigned to receive an
      intravenous infusion of either placebo or drotrecogin alfa activated (24 microg
      per kilogram of body weight per hour) for a total duration of 96 hours. The
      prospectively defined primary end point was death from any cause and was assessed
      28 days after the start of the infusion. Patients were monitored for adverse
      events; changes in vital signs, laboratory variables, and the results of
      microbiologic cultures; and the development of neutralizing antibodies against
      activated protein C. RESULTS: A total of 1690 randomized patients were treated
      (840 in the placebo group and 850 in the drotrecogin alfa activated group). The
      mortality rate was 30.8 percent in the placebo group and 24.7 percent in the
      drotrecogin alfa activated group. On the basis of the prospectively defined
      primary analysis, treatment with drotrecogin alfa activated was associated with a
      reduction in the relative risk of death of 19.4 percent (95 percent confidence
      interval, 6.6 to 30.5) and an absolute reduction in the risk of death of 6.1
      percent (P=0.005). The incidence of serious bleeding was higher in the
      drotrecogin alfa activated group than in the placebo group (3.5 percent vs. 2.0
      percent, P=0.06). CONCLUSIONS: Treatment with drotrecogin alfa activated
      significantly reduces mortality in patients with severe sepsis and may be
      associated with an increased risk of bleeding.

PMID- 11236775
TI  - Initial plasma HIV-1 RNA levels and progression to AIDS in women and men.
AB  - BACKGROUND: It is unclear whether there are differences between men and women
      with human immunodeficiency virus type 1 (HIV-1) infection in the plasma level of
      viral RNA (the viral load). In men, the initial viral load after seroconversion
      predicts the likelihood of progression to the acquired immunodeficiency syndrome
      (AIDS), but the relation between the two has not been assessed in women.
      Currently, the guidelines for initiating antiretroviral therapy are applied
      uniformly to women and men. METHODS: From 1988 through 1998, the viral load and
      the CD4+ lymphocyte count were measured approximately every six months in 156
      male and 46 female injection-drug users who were followed prospectively after HIV
      1 seroconversion. RESULTS: The median initial viral load was 50,766 copies of HIV
      1 RNA per milliliter in the men but only 15,103 copies per milliliter in the
      women (P<0.001). The median initial CD4+ count did not differ significantly
      according to sex (659 and 672 cells per cubic millimeter, respectively). HIV-1
      infection progressed to AIDS in 29 men and 15 women, and the risk of progression
      did not differ significantly according to sex. For each increase of 1 log in the
      viral load (on a base 10 scale), the hazard ratio for progression to AIDS was
      1.55 (95 percent confidence interval, 0.97 to 2.47) among the men and 1.43 (95
      percent confidence interval, 0.76 to 2.69) among the women. The median initial
      viral load was 77,822 HIV-1 RNA copies per milliliter in the men in whom AIDS
      developed and 40,634 copies per milliliter in the men in whom it did not; the
      corresponding values in the women were 17,149 and 12,043 copies per milliliter.
      Given the recommendation that treatment should be initiated when the viral load
      reaches 20,000 copies per milliliter, 74 percent of the men but only 37 percent
      of the women in our study would have been eligible for therapy at the first visit
      after seroconversion (P<0.001). CONCLUSIONS: Although the initial level of HIV-1
      RNA was lower in women than in men, the rates of progression to AIDS were
      similar. Treatment guidelines that are based on the viral load, rather than the
      CD4+ lymphocyte count, will lead to differences in eligibility for antiretroviral
      treatment according to sex.

PMID- 11236774
TI  - Transplantation of embryonic dopamine neurons for severe Parkinson's disease.
AB  - BACKGROUND: Transplantation of human embryonic dopamine neurons into the brains
      of patients with Parkinson's disease has proved beneficial in open clinical
      trials. However, whether this intervention would be more effective than sham
      surgery in a controlled trial is not known. METHODS: We randomly assigned 40
      patients who were 34 to 75 years of age and had severe Parkinson's disease (mean
      duration, 14 years) to receive a transplant of nerve cells or sham surgery; all
      were to be followed in a double-blind manner for one year. In the transplant
      recipients, cultured mesencephalic tissue from four embryos was implanted into
      the putamen bilaterally. In the patients who received sham surgery, holes were
      drilled in the skull but the dura was not penetrated. The primary outcome was a
      subjective global rating of the change in the severity of disease, scored on a
      scale of -3.0 to 3.0 at one year, with negative scores indicating a worsening of
      symptoms and positive scores an improvement. RESULTS: The mean (+/-SD) scores on
      the global rating scale for improvement or deterioration at one year were 0.0+/
      2.1 in the transplantation group and -0.4+/-1.7 in the sham-surgery group. Among
      younger patients (60 years old or younger), standardized tests of Parkinson's
      disease revealed significant improvement in the transplantation group as compared
      with the sham-surgery group when patients were tested in the morning before
      receiving medication (P=0.01 for scores on the Unified Parkinson's Disease Rating
      Scale; P=0.006 for the Schwab and England score). There was no significant
      improvement in older patients in the transplantation group. Fiber outgrowth from
      the transplanted neurons was detected in 17 of the 20 patients in the
      transplantation group, as indicated by an increase in 18F-fluorodopa uptake on
      positron-emission tomography or postmortem examination. After improvement in the
      first year, dystonia and dyskinesias recurred in 15 percent of the patients who
      received transplants, even after reduction or discontinuation of the dose of
      levodopa. CONCLUSIONS: Human embryonic dopamine-neuron transplants survive in
      patients with severe Parkinson's disease and result in some clinical benefit in
      younger but not in older patients.

PMID- 11236776
TI  - Effect of the use or nonuse of long-term dialysis on the subsequent survival of
      renal transplants from living donors.
AB  - BACKGROUND: The effect on allograft survival of the transplantation of kidneys
      from living donors without the previous initiation of long-term dialysis is
      controversial. METHODS: Using data from the U.S. Renal Data System, we performed
      a retrospective cohort study of 8481 patients who were or who were not treated by
      long-term dialysis before receiving a kidney transplant from a living donor. The
      relative rate of allograft failure for patients who received a transplant without
      previously undergoing long-term dialysis, as compared with patients who underwent
      long-term dialysis before transplantation, was assessed by proportional-hazards
      analysis, with adjustment for potential confounding variables, including the
      transplantation center and median household income. The association between the
      receipt of a kidney transplant from a living donor without previous dialysis
      ("preemptive transplantation") and the risk of biopsy-confirmed acute rejection
      within six months after transplantation was evaluated by conditional logistic
      regression analysis, with adjustment for the transplantation center. RESULTS:
      Transplantation of a kidney from a living donor without previous long-term
      dialysis was associated with a 52 percent reduction in the risk of allograft
      failure during the first year after transplantation (rate ratio, 0.48; P=0.002),
      an 82 percent reduction during the second year (rate ratio, 0.18; P=0.001), and
      an 86 percent reduction during subsequent years (rate ratio, 0.14; P=0.001), as
      compared with transplantation after dialysis. The reduction in the rate of
      allograft failure during the first year was attenuated when adjustment was made
      for the timing of acute rejection within the first year (rate ratio, 0.69; 95
      percent confidence interval, 0.44 to 1.10; P=0.10). Increasing duration of
      dialysis was associated with increasing odds of rejection within six months after
      transplantation (P=0.001). CONCLUSIONS: Preemptive transplantation of kidneys
      from living donors without the previous initiation of dialysis is associated with
      longer allograft survival than transplantation performed after the initiation of
      dialysis.

PMID- 11236777
TI  - High serum IgG4 concentrations in patients with sclerosing pancreatitis.
AB  - BACKGROUND: Sclerosing pancreatitis is a unique form of pancreatitis that is
      characterized by irregular narrowing of the main pancreatic duct,
      lymphoplasmacytic inflammation of the pancreas, and hypergammaglobulinemia and
      that responds to glucocorticoid treatment. Preliminary studies suggested that
      serum IgG4 concentrations are elevated in this disease but not in other diseases
      of the pancreas or biliary tract. METHODS: We measured serum IgG4 concentrations
      using single radial immunodiffusion and an enzyme-linked immunosorbent assay in
      20 patients with sclerosing pancreatitis, 20 age- and sex-matched normal
      subjects, and 154 patients with pancreatic cancer, ordinary chronic pancreatitis,
      primary biliary cirrhosis, primary sclerosing cholangitis, or Sjogren's syndrome.
      Serum concentrations of immune complexes and the IgG4 subclass of immune
      complexes were determined by means of an enzyme-linked immunosorbent assay with
      monoclonal rheumatoid factor. RESULTS: The median serum IgG4 concentration in the
      patients with sclerosing pancreatitis was 663 mg per deciliter (5th and 95th
      percentiles, 136 and 1150), as compared with 51 mg per deciliter (5th and 95th
      percentiles, 15 and 128) in normal subjects (P<0.001). The serum IgG4
      concentrations in the other groups of patients were similar to those in the
      normal subjects. In patients with sclerosing pancreatitis, serum concentrations
      of immune complexes and the IgG4 subclass of immune complexes were significantly
      higher before glucocorticoid therapy than after four weeks of such therapy.
      Glucocorticoid therapy induced clinical remissions and significantly decreased
      serum concentrations of IgG4, immune complexes, and the IgG4 subclass of immune
      complexes. CONCLUSIONS: Patients with sclerosing pancreatitis have high serum
      IgG4 concentrations, providing a useful means of distinguishing this disorder
      from other diseases of the pancreas or biliary tract.

PMID- 11236778
TI  - Images in clinical medicine. Choroidal ischemia in preeclampsia.

PMID- 11236779
TI  - Interventional pulmonology.

PMID- 11236780
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 7-2001. A male infant with a right maxillary mass.

PMID- 11236781
TI  - Severe sepsis--a new treatment with both anticoagulant and antiinflammatory
      properties.

PMID- 11236782
TI  - Designing and funding clinical trials of novel therapies.

PMID- 11236783
TI  - Cell therapy for Parkinson's disease.

PMID- 11236784
TI  - Controlling health care expenditures.

PMID- 11236785
TI  - Automated external defibrillators.

PMID- 11236786
TI  - Automated external defibrillators.

PMID- 11236787
TI  - Automated external defibrillators.

PMID- 11236788
TI  - Automated external defibrillators.

PMID- 11236789
TI  - The treatment of babesiosis.

PMID- 11236790
TI  - The treatment of babesiosis.

PMID- 11236791
TI  - Appropriateness of coronary angiography after myocardial infarction among
      Medicare beneficiaries.

PMID- 11236792
TI  - Appropriateness of coronary angiography after myocardial infarction among
      Medicare beneficiaries.

PMID- 11236793
TI  - Appropriateness of coronary angiography after myocardial infarction among
      Medicare beneficiaries.

PMID- 11236795
TI  - MRI-guided diagnosis and treatment of prostate cancer.

PMID- 11236794
TI  - Stem-cell transplantation for myelofibrosis.

PMID- 11236796
TI  - Evaluation of Carcinogenic Risks to Humans: some industrial chemicals. 15-22
      February 2000, Lyon, France.

PMID- 11236797
TI  - From the Centers for Disease Control and Prevention. Recommended childhood
      immunization schedule--United States, 2001.

PMID- 11236798
TI  - From the Centers for Disease Control and Prevention. Underdiagnosis of dengue-
      Laredo, Texas, 1999.

PMID- 11236799
TI  - From the Centers for Disease Control and Prevention. Health-related quality of
      life among persons with epilepsy--Texas, 1998.

PMID- 11236800
TI  - JAMA patient page. Hospice care.

PMID- 11236801
TI  - American College of  Healthcare Executives. Ethics Self-Assessment.

PMID- 11236802
TI  - The place of the osteopathic concept in the healing art. 1947.

PMID- 11236803
TI  - Osteopathy--fifty years later. Founders Memorial Lecture. 1951.

PMID- 11236804
TI  - [Malignant melanoma. Less recurrence with interferon].

PMID- 11236805
TI  - Respiratory distress in heavier versus lighter twins.
AB  - We performed a retrospective study of twin pairs under 36 weeks gestation
      admitted to a regional neonatal unit over a three year period to determine if the
      larger twin of a twin pair is at increased risk of respiratory distress in the
      immediate postnatal period compared to the smaller twin. Gestation, gender, birth
      weight, mode and reason for delivery, birth order, and Apgar at 5 minutes were
      correlated with the need for added oxygen at 4 hours, the need for ventilation,
      oxygen requirement at 28 days and mortality. One hundred and twenty-four twin
      pairs were analyzed with a median gestation of 31 weeks (range 23-35). There were
      47 female-female pairs, 40 male-male pairs and 37 mixed pairs. Multiple logistic
      regression revealed no significant increased risk for ventilation in male,
      heavier or second twins. The need for oxygen at 4 hours was strongly associated
      with being male and being the second twin, but not with being the heavier twin.
      However, on analysis of twins of 28 weeks gestation or above a significant
      association was found between a persisting oxygen requirement at 4 hours and
      being male (OR 2.2; 95% CI 1.15-4.16), being the heavier twin (OR 1.9; 95% CI
      1.03-3.46), and being the second twin (OR 2.7; 95% CI 1.48-4.99). No association
      was found between mortality and being male, and being the second or smaller
      twins. CONCLUSION: Heavier twins above 28 weeks gestation are at increased risk
      of short term mild respiratory problems following delivery compared to lighter
      twins at the same gestation. This is not as strong a factor as birth order or
      male gender, but it is important to be aware of this in antenatal counselling of
      the parents as the smaller twin is usually perceived to be at greater risk of
      morbidity.

PMID- 11236807
TI  - A brief introduction to Monte Carlo simulation.
AB  - Simulation affects our life every day through our interactions with the
      automobile, airline and entertainment industries, just to name a few. The use of
      simulation in drug development is relatively new, but its use is increasing in
      relation to the speed at which modern computers run. One well known example of
      simulation in drug development is molecular modelling. Another use of simulation
      that is being seen recently in drug development is Monte Carlo simulation of
      clinical trials. Monte Carlo simulation differs from traditional simulation in
      that the model parameters are treated as stochastic or random variables, rather
      than as fixed values. The purpose of this paper is to provide a brief
      introduction to Monte Carlo simulation methods.

PMID- 11236806
TI  - The physiological kinetics of nitrogen and the prevention of decompression
      sickness.
AB  - Decompression sickness (DCS) is a potentially crippling disease caused by
      intracorporeal bubble formation during or after decompression from a compressed
      gas underwater dive. Bubbles most commonly evolve from dissolved inert gas
      accumulated during the exposure to increased ambient pressure. Most diving is
      performed breathing air, and the inert gas of interest is nitrogen. Divers use
      algorithms based on nitrogen kinetic models to plan the duration and degree of
      exposure to increased ambient pressure and to control their ascent rate. However,
      even correct execution of dives planned using such algorithms often results in
      bubble formation and may result in DCS. This reflects the importance of
      idiosyncratic host factors that are difficult to model, and deficiencies in
      current nitrogen kinetic models. Models describing the exchange of nitrogen
      between tissues and blood may be based on distributed capillary units or lumped
      compartments, either of which may be perfusion- or diffusion-limited. However,
      such simplistic models are usually poor predictors of experimental nitrogen
      kinetics at the organ or tissue level, probably because they fail to account for
      factors such as heterogeneity in both tissue composition and blood perfusion and
      non-capillary exchange mechanisms. The modelling of safe decompression procedures
      is further complicated by incomplete understanding of the processes that
      determine bubble formation. Moreover, any formation of bubbles during
      decompression alters subsequent nitrogen kinetics. Although these factors mandate
      complex resolutions to account for the interaction between dissolved nitrogen
      kinetics and bubble formation and growth, most decompression schedules are based
      on relatively simple perfusion-limited lumped compartment models of blood: tissue
      nitrogen exchange. Not surprisingly, all models inevitably require empirical
      adjustment based on outcomes in the field. Improvements in the predictive power
      of decompression calculations are being achieved using probabilistic bubble
      models, but divers will always be subject to the possibility of developing DCS
      despite adherence to prescribed limits.

PMID- 11236808
TI  - The pharmacokinetics of levosalbutamol: what are the clinical implications?
AB  - Salbutamol (albuterol) is a beta2-adrenoceptor agonist used as a bronchodilator
      for the treatment of asthma and as a uterine relaxant for the suspension of
      premature labour. Salbutamol has been marketed as a racemic mixture, although
      beta2-agonist activity resides almost exclusively in the (R)-enantiomer. The
      enantioselective disposition of salbutamol and the possibility that (S)
      salbutamol has adverse effects have led to the development of an enantiomerically
      pure (R)-salbutamol formulation known as levosalbutamol (levalbuterol).
      Salbutamol is metabolised almost exclusively by sulphotransferase (SULT) 1A3 to
      an inactive metabolite. (R)-Salbutamol is metabolised up to 12 times faster than
      (S)-salbutamol. This leads to relatively higher plasma concentrations of (S)-
      salbutamol following all routes of administration, but particularly following
      oral administration because of extensive metabolism by the intestine. Enantiomer
      concentrations are similar for the first hour following an inhaled dose,
      reflecting the fact that salbutamol in the lung probably undergoes little
      metabolism. Subsequently, (S)-salbutamol predominates due to absorption and
      metabolism of the swallowed portion of the inhaled dose. Following oral or
      inhaled administration of enantiomerically pure salbutamol, a small amount (6%)
      is converted to the other enantiomer, probably by acid-catalysed racemisation in
      the stomach. Tissue binding of salbutamol is not enantioselective and plasma
      protein binding is relatively low. Both enantiomers are actively excreted into
      the urine. Compared with healthy individuals, patients with asthma do not have
      substantially different pharmacokinetics of the salbutamol enantiomers, but they
      do appear to have less drug delivered to the lung following inhaled
      administration because of their narrowed airways. Levosalbutamol elicits an equal
      or slightly larger response than an equivalent dose of the racemic mixture. This
      is probably due to competitive inhibition between the enantiomers at beta
      adrenoceptors. Pharmacokinetic-pharmacodynamic relationships for levosalbutamol
      show relatively large interindividual variations. Functionally significant
      genetic polymorphisms have been identified for beta2-adrenoceptors, SULT1A3 and
      organic action transporters, all of which affect the disposition or action of
      levosalbutamol. Animal, in vitro and some clinical studies have reported
      deleterious effects of (S)-salbutamol on smooth muscle contractility or lung
      function. However, well-designed clinical studies in patients with asthma have
      failed to find evidence of significant toxicity associated with (S)-salbutamol.
      The clinical consequences of relatively higher plasma concentrations of (S)
      salbutamol following administration of racemate remain unclear, but in the
      absence of clear evidence of toxicity the clinical superiority of levosalbutamol
      over racemic salbutamol appears to be small.

PMID- 11236811
TI  - Serial sexual homicide: biological, psychological, and sociological aspects.

PMID- 11236810
TI  - Covariate effects on the apparent clearance of tacrolimus in paediatric liver
      transplant patients undergoing conversion therapy.
AB  - OBJECTIVE: To analyse the influence of covariates on the apparent clearance (CL)
      of tacrolimus in paediatric liver transplant recipients being converted from
      cyclosporin to tacrolimus. DESIGN: Retrospective modelling study. PATIENTS AND
      PARTICIPANTS: 18 children, 13 girls and 5 boys, aged 4 months to 16 years (median
      9.1 years) who required conversion to tacrolimus because of acute or chronic
      rejection or cyclosporin toxicity. METHODS: 287 whole-blood tacrolimus
      concentrations from therapeutic drug monitoring were used to build a nonlinear
      mixed-effects population model (NONMEM program) for the apparent clearance of
      tacrolimus. Variables considered were age, total bodyweight (TBW), body surface
      area (BSA), time after initiation of treatment (T), gender, haematocrit (Hct),
      albumin (Alb), aspartate aminotransferase (AST), alanine aminotransferase (ALT),
      gamma-glutamyl transpeptidase (gammaGT), alkaline phosphatase (ALP), bilirubin
      (BIL), creatinine clearance (CL(CR)) and dosage of concomitant corticosteroids
      (EST). RESULTS: TBW, T, BIL and ALT were the covariates that displayed a
      significant influence on CL according to the final regression model: CL (L/h) =
      10.4(TBW/70)3/4 x e(-0.00032 T) x e(-0.057 BIL) x (1 - 0.079 ALT). With this
      model, the estimates of the coefficients of variation were 24.3% and 29.5% for
      interpatient variability in CL and residual variability, respectively.
      CONCLUSIONS: The proposed model for tacrolimus CL can be applied for a priori
      dosage calculations, although the results should be used with caution because of
      the unexplained variability in the CL. We therefore recommended close monitoring
      of tacrolimus whole blood concentrations, especially within the first months of
      treatment. The best use of the model would be its application in dosage
      adjustment based on therapeutic drug monitoring and the Bayesian approach.

PMID- 11236812
TI  - Relationships of borderline features to parental mental illness, childhood abuse,
      Axis I disorder, and current functioning.
AB  - Although a number of studies have investigated single, putative etiological
      factors for borderline personality disorder (BPD), few studies have assessed the
      relations between multiple etiological factors and borderline features within the
      same study. Borderline features, parental psychopathology, childhood physical and
      sexual abuse, lifetime Axis I disorder, and current functioning were assessed in
      65 nonclinical participants, a portion of which exhibited significant BPD
      features. Multivariate models were tested and results indicated that parental
      mental illness and lifetime Axis I disorder were significant and unique
      predictors of borderline scores. Borderline features accounted for significant
      variance in current functioning beyond what was accounted for by other
      predictors; borderline scores mediated the relations between lifetime Axis I
      disorder and current functioning.

PMID- 11236813
TI  - Heritability of personality disorders in childhood: a preliminary investigation.
AB  - The heritability of personality disorder features was investigated in 112 child
      (ages 4-15 years) twin pairs (70 monozygotic and 42 dizygotic pairs). Parents
      assessed personality disorder features using the Coolidge Personality and
      Neuropsychological Inventory for Children (CPNI; Coolidge, 1998) that measures 12
      personality disorders according to the criteria in the Diagnostic and Statistical
      Manual of Mental Disorders (DSM-IV) (American Psychiatric Association, 1994).
      Structural equation model-fitting methods indicated that the median heritability
      coefficient for the 12 scales was .75 (ranging from .81 for the Dependent and
      Schizotypal Personality Disorder scales to .50 for the Paranoid and Passive
      Aggressive Personality Disorder scales). These results suggest that childhood
      personality disorders have a substantial genetic component and that they are
      similar to heritability estimates of personality disorder traits in adults and
      counter hypotheses that only temperaments and higher-order personality disorder
      traits have significant genetic components (Paris, 1997).

PMID- 11236814
TI  - Effects of sex and sex roles on the perceived maladaptiveness of DSM-IV
      personality disorder symptoms.
AB  - This study investigated the influence of sex on the perceived maladaptiveness of
      DSM-IV personality disorder criteria based on previous findings that
      inconsistency of symptoms with sex roles affects the perception of personality
      disorder symptoms. The effects of rater characteristics (i.e., sex, sex role)
      were also examined. A total of 161 undergraduates (65 men, 96 women) rated the
      diagnostic criteria according to how maladaptive they were for males (male
      condition), females (female condition), or without regard to sex (neutral
      condition that served as a baseline) using a 7-point scale. Participants' sex
      role was determined using the Bem Sex Role (1981a) Inventory. Dependent and
      depressive personality disorder criteria (trend for borderline) were rated more
      maladaptive for females than males, whereas obsessive-compulsive personality
      disorder criteria were rated more maladaptive for males than females. Participant
      sex and sex role had little or no significant effects on the ratings. Results are
      compared with those of previous research. Methodological issues and implications
      for the diagnosis of personality disorders are discussed.

PMID- 11236815
TI  - Patterns of personality pathology in patients with generalized anxiety disorder,
      panic disorder with and without agoraphobia, and social phobia.
AB  - The relationship between co-occurring personality disorders and anxiety disorders
      (panic disorder with or without agoraphobia, social phobia, and generalized
      anxiety disorder) was examined, taking into account the effect of major
      depression. This article describes findings for 622 participants in the
      Harvard/Brown Anxiety Research Project, a longitudinal follow-up study of DSM-III
      R-defined anxiety disorders. A total of 24% of participants had at least one
      personality disorder, with avoidant, obsessive compulsive, dependent, and
      borderline most common. Generalized anxiety disorder, social phobia, and major
      depression were positively associated with the occurrence of one or more
      personality disorders, whereas panic disorder with agoraphobia was not
      associated. Major depression was associated in particular with dependent,
      borderline, histrionic, and obsessive compulsive personality disorders and social
      phobia was associated with avoidant personality disorder. Whereas some of our
      findings confirm results from earlier studies, others are somewhat inconsistent
      with previous results and indicate the need for further investigation.

PMID- 11236816
TI  - Addicted patients with personality disorders: traits, schemas, and presenting
      problems.
AB  - We evaluated the association of Structure Clinical Interview for the DSM-IV Axis
      II (SCID-II) severity and personality traits, early maladaptive schemas, and
      presenting symptoms in 41 methadone-maintained patients meeting criteria for
      either antisocial, borderline, avoidant, or depressive personality disorder.
      Correlational analyses indicated that the severity of each personality disorder
      was associated with a unique profile of presenting problems and underlying traits
      and schemas. The evaluation of multiple psychological indicators appears to be a
      useful method for case conceptualization and planning interventions within a
      promising individual therapy model that focuses both on substance abuse and
      psychiatric symptoms and maladaptive schemas and coping styles.

PMID- 11236809
TI  - Clinical pharmacokinetics and pharmacodynamics of ifosfamide and its metabolites.
AB  - This review discusses several issues in the clinical pharmacology of the
      antitumour agent ifosfamide and its metabolites. Ifosfamide is effective in a
      large number of malignant diseases. Its use, however, can be accompanied by
      haematological toxicity, neurotoxicity and nephrotoxicity. Since its development
      in the middle of the 1960s, most of the extensive metabolism of ifosfamide has
      been elucidated. Identification of specific isoenzymes responsible for ifosfamide
      metabolism may lead to an improved efficacy/toxicity ratio by modulation of the
      metabolic pathways. Whether ifosfamide is specifically transported by
      erythrocytes and which activated ifosfamide metabolites play a key role in this
      transport is currently being debated. In most clinical pharmacokinetic studies,
      the phenomenon of autoinduction has been observed, but the mechanism is not
      completely understood. Assessment of the pharmacokinetics of ifosfamide and
      metabolites has long been impaired by the lack of reliable bioanalytical assays.
      The recent development of improved bioanalytical assays has changed this
      dramatically, allowing extensive pharmacokinetic assessment, identifying key
      issues such as population differences in pharmacokinetic parameters, differences
      in elimination dependent upon route and schedule of administration, implications
      of the chirality of the drug and interpatient pharmacokinetic variability. The
      mechanisms of action of cytotoxicity, neurotoxicity, urotoxicity and
      nephrotoxicity have been pivotal issues in the assessment of the pharmacodynamics
      of ifosfamide. Correlations between the new insights into ifosfamide metabolism,
      pharmacokinetics and pharmacodynamics will rationalise the further development of
      therapeutic drug monitoring and dose individualisation of ifosfamide treatment.

PMID- 11236817
TI  - Chronic, low-grade depression in a nonclinical sample: depressive personality or
      dysthymia?
AB  - Depressive personality disorder (DPD) is being considered for inclusion in future
      editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM).
      However, there is substantial conceptual and empirical overlap between DPD and
      dysthymic disorder (Dysthymia) criteria, suggesting that these two constructs may
      not be distinct. Confirmatory factor analysis of the DPD traits and dysthymia
      symptoms in a large, nonclinical sample (N = 368) indicated that a two-factor
      model was a better fit than a one-factor model. However, binary diagnostic
      analysis revealed that over half of the individuals meeting criteria for DPD also
      met criteria for dysthymia and that the best-fitting model allowed the
      psychological symptoms of dysthymia to load on both DPD and dysthymia latent
      factors. All of the individuals with DPD alone failed to meet criteria for
      dysthymia because they did not report chronic depressed mood. Our results suggest
      that although DPD is not synonymous with Dysthymia, it may be a milder subtype.

PMID- 11236818
TI  - A randomized controlled trial of community-oriented and hospital-oriented care
      for discharged psychiatric patients: influence of personality disorder on police
      contacts.
AB  - An important forensic psychiatric measure, contacts with police, was compared in
      a randomized, controlled trial of 155 patients with severe mental illness with a
      previous admission within the past two years. The patients, who also had their
      personality status addressed formally before randomization, were allocated to
      community multidisciplinary teams or to hospital-based care programs after
      discharge from in-patient care and were followed up for one year. A total of 138
      patients (89%) had at least one post-baseline assessment and of these patients,
      16 (12%) had at least one police contact in the year of the study, most of which
      were emergency assessments. The data showed significantly greater numbers of
      police contacts in patients with increasing severity of personality disturbance.
      Patients with such disturbance were six times more likely to have police contacts
      than those with no personality disorder. There were significantly more contacts
      in patients with borderline and antisocial (dissocial) personality disorder
      allocated to community-oriented care compared with hospital-oriented care. These
      findings have important implications for risk assessment in severe mental
      illness.

PMID- 11236819
TI  - Cognitive intervention in Alzheimer disease: a randomized placebo-controlled
      study.
AB  - The efficacy of a cognitive intervention consisting of training in face-name
      associations, spaced retrieval, and cognitive stimulation was tested in a sample
      of 37 patients (16 men, 21 women) with probable Alzheimer disease (AD). Patients
      with AD were randomly assigned to receive either the cognitive intervention or a
      mock (placebo) intervention for 5 weeks. The placebo group then crossed over to
      receive the intervention. During the intervention, AD patients showed significant
      improvement in recall of personal information, face-name recall, and performance
      on the Verbal Series Attention Test. Improvement did not generalize to additional
      neuropsychologic measures of dementia severity, verbal memory, visual memory,
      word generation, or motor speed, or to caregiver-assessed patient quality of
      life. Results suggest that although face-name training, spaced retrieval, and
      cognitive stimulation may produce small gains in learning personal information
      and on a measure of attention, improvement does not generalize to overall
      neuropsychologic functioning or patient quality of life.

PMID- 11236820
TI  - Simulated car crashes at intersections in drivers with Alzheimer disease.
AB  - Current evidence suggests that car crashes in cognitively impaired older drivers
      often occur because of failure to notice other drivers at intersections. We
      tested whether licensed drivers with mild to moderate cognitive impairment due to
      Alzheimer disease (AD) are at greater risk for intersection crashes. In this
      experiment, 30 participants drove on a virtual highway in a simulator scenario
      where the approach to within 3.6 seconds of an intersection triggered an illegal
      incursion by another vehicle. To avoid collision with the incurring vehicle, the
      driver had to perceive, attend to, and interpret the roadway situation; formulate
      an evasive plan; and then exert appropriate action on the accelerator, brake, or
      steering controls, all under pressure of time. The results showed that 6 of 18
      drivers with AD (33%) experienced crashes versus none of 12 nondemented drivers
      of similar age. Use of a visual tool that plots control over steering wheel
      position, brake and accelerator pedals, vehicle speed, and vehicle position
      during the 5 seconds preceding a crash event showed inattention and control
      responses that were either inappropriate or too slow. The findings were combined
      with those in another recent study of collision avoidance in drivers with AD that
      focused on potential rear end collisions. Predictors of crashes in the combined
      studies included visuospatial impairment, disordered attention, reduced
      processing of visual motion cues, and overall cognitive decline. The results help
      to specify the linkage between decline in certain cognitive domains and increased
      crash risk in AD and also support the use of high-fidelity simulation and
      neuropsychologic assessment in an effort to standardize the assessment of fitness
      to drive in persons with medical impairments.

PMID- 11236821
TI  - Descriptive analysis of emergency hospital admissions of patients with Alzheimer
      disease.
AB  - The aim of this project was to study the underlying reasons for emergency
      hospital admission of patients with dementia of the Alzheimer type (DAT) and
      their characteristics. This prospective 4-month study identified 118 patients
      with DAT, most of whom were referred to the two emergency departments of the
      Toulouse University Hospital. The two main reasons for admission were behavioral
      problems (26.3%) and falls (18.6%). Patients were generally at an advanced stage
      of the disease process and had substantial evidence of poor nutritional status
      and loss of activities of daily living ability. About one third of patients had
      already been admitted to the hospital for the same reasons in the preceding
      months. Psychotropic drugs predominated (71%) among the current medications taken
      by the patients and were mainly anxiolytics and neuroleptics. Finally, the
      discharge report indicated that medications were a contributing factor in the
      disorders of 25% of patients. We believe that improved information for caregivers
      and early management and treatment are essential to respond adequately to the
      problems raised by this population.

PMID- 11236822
TI  - Meeting the need for public education about dementia.
AB  - Research continues to advance the knowledge of pathophysiology and development of
      effective methods for treating patients with Alzheimer disease and other
      dementias. Dissemination of information is likely to be slowest among the general
      population, who may be the first to recognize dementia symptoms but may also be
      reticent to discuss concerns because of fear, embarrassment, and/or inadequate
      knowledge. The feasibility of providing public education and access to dementia
      resources was studied using a toll-free interactive voice response (IVR)
      telephone system. Public interest in this service and willingness to use this
      technology were evaluated in a 1-month study conducted in a predominantly rural
      upper Midwest county (population of 102,565). One hundred ninety-three calls were
      received during November 1999, with an average length of 9 minutes and 29
      seconds. One in six calls lasted 15 minutes or longer. One third of the calls
      were received outside typical business hours (8:00 AM to 6:00 PM). Concern for a
      parent or grandparent was the most frequent reason (50.6%) given for the call.
      Self-concern was indicated by 24.7% of the callers. Callers provided positive
      feedback. Such IVR technology may provide a cost-effective bridge to the "digital
      divide" existing among elderly, lower socioeconomic status, and rural populations
      underrepresented as computer and Internet users.

PMID- 11236823
TI  - Clinical and pathologic features of two groups of patients with dementia with
      Lewy bodies: effect of coexisting Alzheimer-type lesion load.
AB  - The objectives of this study were to examine the clinical and pathologic features
      of two subgroups of patients with dementia with Lewy bodies (DLB) differing in
      Alzheimer disease (AD)-type pathology load and to identify clinical variables
      useful in the differential diagnosis from AD. The records of 64 consecutive
      demented patients were reviewed. Pathologic diagnoses were independently
      established [35 AD cases, 11 cases of pure dementia with Lewy bodies (pDLB), and
      18 cases of combined AD plus Lewy bodies (AD+LB)], and several neurodegenerative
      lesions were quantified. Clinical and pathologic data were compared between
      groups with univariate and multivariate analyses. Compared with the other groups,
      pDLB cases had more frequent acute-subacute onset of dementia [45% vs. AD (3%)
      and AD+LB (16%)], early parkinsonism [45% vs. AD (0%) and AD+LB (0%)], early [27%
      vs. AD (0%) and AD+LB (0%)] and late [73% vs. AD (11%) and AD+LB (16%)]
      hallucinations, fluctuating course [46% vs. AD (9%) and AD+LB (22%)], delusions
      [45% vs. AD (11%) and AD+LB (6%)], spontaneous parkinsonism [63% vs. AD (8%) and
      AD+LB (16%)], less frequent ideomotor apraxia and loss of insight, earlier
      urinary incontinence [3.2 +/- 1.4 years after onset vs. AD (6.3 years) and AD+LB
      (5.8 years)], shorter duration of dementia [7.7 +/- 2.4 years vs. AD (9.6 years)
      and AD+LB (11 years)], milder atrophy in computed tomography scans, greater brain
      weight, more transcortical spongiosis, wider cortex and subcortex, and less
      amyloid angiopathy. All pDLB cases but no AD cases had abnormal CA2 neurites. The
      clinical features of AD+LB patients were similar to those of AD patients other
      than more frequent acute-subacute onset and fluctuating evolution. Discriminant
      analyses selected four clinical variables differentiating pDLB from the other two
      groups as a whole: acute-subacute onset, early parkinsonism, early
      hallucinations, and early onset of urinary incontinence. Two or more of these
      features identified pDLB with a sensitivity of 81.8% and a specificity of 95.9%.
      Differentiation between the three groups (pDLB, AD+LB, and AD) or between both
      groups with LB (DLB) from AD could be only attained in 70% of cases. We conclude
      that early symptomatology is the main clue for the diagnosis of pDLB. We
      identified by discriminant analysis a set of clinical diagnostic criteria similar
      to those proposed by the Consortium on Dementia With Lewy Bodies. Accuracy was
      excellent for the diagnosis of pDLB but only mediocre for separating AD+LB as
      well as the entire DLB group from AD.

PMID- 11236824
TI  - Activation mechanism of brain microglia in patients with diffuse neurofibrillary
      tangles with calcification: a comparison with Alzheimer disease.
AB  - Diffuse neurofibrillary tangles with calcification (DNTC) is an atypical dementia
      and is characterized pathologically by diffuse neurofibrillary tangles (NFTs)
      without senile plaques (SPs). In this study, we investigated the distribution of
      human leukocyte antigen (HLA)-DR-positive activated microglia in postmortem brain
      tissue of six patients with DNTC and six patients with Alzheimer disease (AD).
      HLA-DR-positive activated microglia were observed to associate with SPs in AD. In
      the DNTC brain, which lacks SPs, HLA-DR-positive microglia were mainly
      accumulated around weakly tau-positive NFTs, which were also positive for anti
      amyloid-P and anti-C3d antibodies. The results of this study suggest that the
      complement pathway is also activated in the DNTC brain and that immune and
      inflammatory responses, including microglia activation, may occur around
      extracellular NFTs in DNTC patients.

PMID- 11236826
TI  - The financial (material) consequences of dementia care in a developing country:
      Nigeria.

PMID- 11236825
TI  - Alpha-1-antichymotrypsin and oxidative stress in the peripheral blood from
      patients with probable Alzheimer disease: a short-term longitudinal study.
AB  - To evaluate the stability and reproducibility of selected peripheral oxidative
      stress markers and their possible relation to cognitive performance, three
      different blood samples were taken at 7- to 10-day intervals from 11 patients
      with probable Alzheimer disease (AD) and 11 nondemented controls. Blood samples
      were also collected once from 6 patients with vascular dementia (VD). Alpha-1
      antichymotrypsin (ACT), C-reactive protein (CRP), glutathione peroxidase (GSH
      Px), superoxide dismutase (SOD), lactoferrin (LTF), and total lipid peroxidation
      (LPO) were then measured. Blood levels of ACT and GSH-Px were increased in AD
      patients but not in patients with VD. Levels of LTF, CRP, and LPO were comparable
      between AD patients and controls. Erythrocyte SOD activity was increased in AD
      patients. Blood levels of ACT negatively correlated with LPO levels and
      positively correlated with scores of the Global Deterioration Scale of AD
      patients. ACT might be implicated in controlling oxidative damage of blood lipids
      and their turnover during the progression of AD.

PMID- 11236827
TI  - Polyphyenolics increase t-PA and u-PA gene transcription in cultured human
      endothelial cells.
AB  - BACKGROUND: Moderate red wine consumption has been associated with a reduced risk
      for coronary heart disease, and this cardioprotection may be mediated, in part,
      by promoting fibrinolysis. This protection may be attributed to the combined or
      perhaps synergistic effects of alcohol and other red wine components (i.e.,
      polyphenolics). These studies were carried out to determine whether individual
      phenolics (i.e., catechin, epicatechin, quercetin, and resveratrol) affect
      fibrinolytic protein (tissue-type plasminogen activator [t-PA] and urokinase-type
      PA [u-PA]) expression and surface-localized fibrinolytic activity in cultured
      human umbilical vein endothelial cells (HUVECs). METHODS: Cultured HUVECs were
      preincubated (1 hr, 37 degrees C) in the absence or presence of varying
      concentrations of catechin, epicatechin, quercetin, and resveratrol (0.001-10
      microM) and then were washed and incubated for various times in the absence of
      phenolics. Secreted t-PA/u-PA antigen (24 hr, enzyme-linked immunoadsorbent
      assay) and mRNA [0-16 hr, reverse transcription-polymerase chain reaction(RT
      PCR)] levels and fibrinolytic activity (direct activation of HUVEC-bound 125I
      labeled glutamylplasminogen, quantitation of 125I-labeled Mr 20 kDa plasmin light
      chain) were measured. Transient transfections of cultured HUVECs were carried out
      with the pt-PA222/luc and pu-PA236/luc promoter constructs, by using
      lipofectamine. RESULTS: Each of the phenolics similarly increased t-PA and u-PA
      antigen (2- to 3-fold) and mRNA (3- to 4-fold) levels, concomitant with an
      increase (2- to 3-fold) in sustained (24 hr), surface-localized fibrinolytic
      activity. Transcription inhibitor actinomycin D abolished the induction of t-PA
      and u-PA mRNA expression by these phenolics. Transfections with the pt-PA222/luc
      and pu-PA236/luc promoter constructs showed 2- to 3-fold and 2- to 4-fold
      increases in luciferase activity for t-PA and u-PA, respectively. CONCLUSIONS:
      These results demonstrate that each of these phenolics up-regulates both t-PA and
      u-PA gene transcription, which results in the sustained increased expression of
      surface-localized fibrinolytic activity in cultured HUVECs. Wine phenolics
      increase fibrinolytic activity, independent of ethanol, and it is likely that the
      overall cardioprotective benefits associated with moderate red wine consumption
      are attributable to the combined, additive, or perhaps synergistic effects of
      alcohol and other wine components.

PMID- 11236828
TI  - Ethanol-induced up-regulation of the urokinase receptor in cultured human
      endothelial cells.
AB  - BACKGROUND: Moderate alcohol consumption has been correlated to reduced coronary
      artery disease (CAD) risk and mortality. This alcohol effect may be mediated in
      part by an increased endothelial cell (EC) fibrinolysis. ECs synthesize
      fibrinolytic proteins, tissue plasminogen activator (t-PA), urokinase type
      plasminogen activator (u-PA), and plasminogen activator inhibitor type-1(PAI-1).
      In addition, they synthesize and regulate receptors for fibrinolytic proteins,
      namely (t-PA and plasminogen receptor) Annexin II and u-PA receptor (u-PAR).
      These receptors play an important role in the regulated expression of receptor
      bound plasminogen activator conversion of receptor-bound plasminogen to receptor
      bound plasmin on the EC surface (surface-localized fibrinolytic activity).
      Therefore, systemic factors, such as ethanol, that affect the level, or activity
      or interaction of one or more of these components, resulting in the increased
      expression of surface-localized EC fibrinolytic activity, will be expected to
      reduce the risk for thrombosis, CAD, and myocardial infarction (MI). We have
      previously shown that low ethanol up-regulates t-PA and u-PA gene transcription,
      while it down-regulates PAI-1, hence resulting in increased (sustained, 24 hr)
      surface-localized EC fibrinolytic activity. The current studies were carried out
      to determine whether low ethanol increased u-PAR expression in cultured human
      umbilical cord vein ECs (HUVECs). METHODS: Cultured HUVECs were preincubated (1
      hr) in the absence/presence of ethanol (0.025-0.2%, v/v); u-PAR mRNA (RT-PCR),
      antigen (western blot), and activity (125I-u-PA ligand binding/Scatchard
      analysis) levels were then measured after 0-24 hr. To determine whether the
      ethanol-induced changes in the u-PAR expression were transcriptional, transient
      transfection studies were carried out using a u-PAR/ luciferase promoter
      construct (pu-PAR120/luc [1.2-kb u-PAR promoter fragment ligated to a
      promoterless luciferase vector]). RESULTS: uPAR mRNA levels increased 2- to 3
      fold and antigen levels (western blot) increased 2- to 4-fold while u-PA binding
      activity increased 36% (1.25 vs. 1.7 x 10(5) sites/cell, Bmax) without
      significantly affecting the Kd (1-2 nM). Transient transfection of cultured
      HUVECs with a pu-PAR120/luc construct resulted in a 2- to 3-fold increase in
      promoter activity in ethanol-induced cultures, compared with controls.
      CONCLUSION: These combined results demonstrate that low ethanol (< or =0.1%, v/v)
      induces the up-regulation of u-PAR gene transcription, resulting in increased u
      PAR ligand binding activity. These results also further identify/define the
      contribution and role of another fibrinolytic protein in the overall ethanol
      induced increase in surface-localized EC fibrinolysis that may underlie and
      contribute, in part, to the cardioprotection attributed to moderate alcohol
      consumption.

PMID- 11236829
TI  - No effect of albinism on sedative-hypnotic sensitivity to ethanol and
      anesthetics.
AB  - BACKGROUND: Studies using the long-sleep (LS) X short-sleep (SS) (LSXSS)
      recombinant inbred mice and inbred long-sleep (ILS) by inbred short-sleep (ISS)
      intercrosses have found genetic linkage between Tyr albinism (c/c) and
      differential sensitivity to sedative-hypnotic doses of ethanol and general
      anesthetics. This linkage could be due to a gene or genes near Tyr or Tyr itself.
      With regard to the latter possibility, the absence of tyrosinase activity
      (encoded by Tyr) in albinos could alter tyrosine availability and thus the rate
      limiting step in catecholamine synthesis. In addition, albinism is associated
      with altered brain development that could have pleiotropic effects on behavior.
      Therefore, in this study, we asked whether albinism affects sedative-hypnotic
      sensitivity. METHODS: Loss of righting reflex (LORR) duration was measured using
      doses of ethanol (4.1 g/kg), pentobarbital (70 mg/kg), isoflurane (2 g/kg), and
      etomidate (20 mg/kg) that were previously associated with differential
      sensitivity of albino versus nonalbino mice. Tyr transgenics (c/c, Tg(Tyr+)) were
      backcrossed to ISS (c/c) to compare pigmented (c/c, Tg(Tyr+)) and albino (c/c)
      mice in the context of an ISS-like background. ISS was also crossed with C57BL/6
      (B6) mice heterozygous for a spontaneous albino mutation (c2j) to compare
      pigmented (c/+) and albino (c/c2j) mice. Pigmented B6 (c2j/+ and +/+) and albino
      B6 (c2j/c2j) mice were also compared (pentobarbital). RESULTS: For each sedative
      hypnotic, albinism had no effect on LORR duration. Each expected difference was
      ruled out at the 95% or 99% confidence level. For each sedative hypnotic, males
      were more sensitive than females even though the effect size was usually smaller
      than the expected albino effect size, arguing empirically that the inability to
      detect an albino effect was not due to systematic error or an insufficient number
      of mice. CONCLUSION: We conclude that the differential sensitivity associated
      with albinism is most likely due to a gene or genes near Tyr rather than Tyr
      itself.

PMID- 11236830
TI  - Dopamine D2 receptor gene (DRD2) is associated with alcoholism with conduct
      disorder.
AB  - This study examined whether there is evidence for an association between
      alcoholism with conduct disorder and alleles of the TaqI A and TaqI B
      polymorphisms, both individually and as haplotypes, at the dopamine D2 receptor
      gene (DRD2). We studied 182 Han Chinese subjects, including 34 alcoholics with
      conduct disorder, 63 alcoholics without conduct disorder, and 85 nonalcoholics.
      Alcohol dependence and conduct disorder were defined according to DSM-III-R
      criteria. Significant associations were observed between TaqI A and TaqI B at the
      DRD2 locus, tested individually and as haplotypes, and alcoholism with conduct
      disorder. Our results suggested that DRD2 might be associated with conduct
      disorder or a predisposition to both conduct disorder and alcoholism. However,
      this needs to be further investigated by examining the differences among conduct
      disorder with alcoholism, conduct disorder only, and controls for the TaqI A and
      B system at DRD2.

PMID- 11236831
TI  - Working memory impairments in alcohol-dependent participants without clinical
      amnesia.
AB  - BACKGROUND: The delayed alternation (DA) task is highly sensitive to the deficits
      of nonhuman animals with alcohol-related brain damage. DA is thought to measure
      working memory which serves as a temporary store for processing of information.
      However, performance on this type of task has only been investigated in alcohol
      dependent humans with severe cognitive deficits. The aim of the current study was
      to explore the validity of DA as a test sensitive to alcohol-related brain damage
      by manipulating storage and processing components in three versions of the task.
      It was hypothesized that alcohol-dependent people would perform worse than
      control participants and that their deficits would be more pronounced in DA
      versions with maximal working memory demands. METHODS: A sample of 12 alcohol
      dependent participants without Wernicke-Korsakoff syndrome was compared with a
      sample of 12 nonalcohol-dependent controls on three versions of DA. These
      versions, in order of increasing working memory demand, were single alternation
      (LR), double alternation (LLRR), and asymmetric alternation (LRRR). DA was
      administered on a personal computer and performance measured by the number of
      trials taken to reach criterion. RESULTS: Alcohol-dependent participants,
      compared with the control participants, took more trials to reach learning
      criterion on DA on all versions when analyzed together (p = 0.002). Performance
      on DA was also found to deteriorate with increased working memory demands in both
      groups of participants (p < 0.001). However, the deficits of alcohol-dependent
      participants were most pronounced on the DA task with moderate (LLRR) as opposed
      to extreme (LRRR) working memory demands. CONCLUSIONS: The results indicate that
      both storage and processing demands are necessary for task performance and
      demonstrate sensitivity of DA to alcohol-related brain injury.

PMID- 11236832
TI  - Maintaining intentional control of behavior under alcohol.
AB  - BACKGROUND: This research used a process dissociation paradigm to measure the
      influence of controlled and automatic processes on a word-stem completion task
      when correct performance under alcohol was positively reinforced, or had no
      particular consequence. It was predicted that the impairing effect of alcohol on
      controlled processes that govern intentional control of behavior would be
      resisted when drinkers were reinforced for performing well. METHODS: Four groups
      of eight male drug-free social drinkers initially studied a list of words. Two of
      the groups then received 0.56 g/kg alcohol (A) and two received a placebo (P)
      before the stem-completion task was performed. During the task, the correct
      responses of one pair of A and P groups were reinforced (money and verbal
      approval) whereas no reinforcement was provided to the other pair. RESULTS: As
      predicted, under alcohol, the influence of controlled processes that govern
      intentional responses was greater when reinforcement was provided than when it
      was absent (p = 0.005). Without reinforcement, controlled processes in the A
      group were lower than the P control group (p = 0.01). In contrast, the A and P
      groups that received reinforcement did not differ (p = 0.142). Controlled
      processes in the P groups were not affected by reinforcement (p = 0.65). In
      addition, the influence of automatic processes was not affected by alcohol or by
      reinforcement (p > 0.781). CONCLUSIONS: Positive reinforcement for behavior under
      alcohol increases the influence of controlled processes. These results suggest
      that the degree to which intentional control is retained under alcohol depends on
      the consequence of behavior in the situation. It seems that controlled processes
      enable drinkers to intentionally display the behavior that is rewarded.

PMID- 11236833
TI  - Neurochemical characteristics associated with ethanol preference in selected
      alcohol-preferring and -nonpreferring rats: a quantitative microdialysis study.
AB  - BACKGROUND: Rodent lines selected for alcohol preference and nonpreference have
      been used extensively to determine the neurobiological basis of alcohol-seeking
      behavior. Evidence suggests that innate differences in the mesolimbic dopamine
      and serotonin systems may contribute to disparate alcohol-seeking behaviors
      between these selected lines. Therefore, the purpose of this study was to
      identify neurochemical characteristics which may predict ethanol preference in
      selected alcohol-preferring and -nonpreferring rats [high-alcohol-preferring
      (HAD), low-alcohol-preferring (LAD), Alko alcohol (AA), Alko nonalcohol (ANA),
      Wistar]. METHODS: Basal release of dopamine (DA) and serotonin (5-HT) in the
      nucleus accumbens of ethanol-naive rats was analyzed for its relationship with
      subsequent measures of ethanol preference. Initially, basal extracellular DA and
      5-HT levels were measured by "no-net-flux" quantitative microdialysis.
      Subsequently, the dopaminergic response to systemic ethanol administration (1.5
      g/kg; intraperitoneal) was determined. After completion of the neurochemical
      tests, the rats received unlimited two-bottle, free-choice access to 10% (w/v)
      ethanol and water in the home cage for 28 days. RESULTS: Analysis of the data
      across individual animals revealed that extracellular dopamine levels ([DA]e; r =
      + 0.64;p < 0.006) and the percent of baseline increase in DA (%incrDA; r = +
      0.77;p < 0.001) due to ethanol were significant predictors of ethanol preference.
      Comparison of the data between genetic lines yielded a significant relationship
      between preference and %incrDA (r = + 0.87; p < 0.05). Analysis of the data
      across animals within each line and their respective control line determined that
      in the AA/ANA line pair (r = + 0.67; p < 0.03) and Wistar line (r = + 0.66; p <
      0.03) %incrDA was a significant predictor of preference. In the HAD/LAD line
      pair, %incrDA (r = + 0.56; p < 0.005) and [DA]e (r = + 0.86; p < 0.004) were
      significant predictors of ethanol preference. CONCLUSIONS: Overall, these
      findings suggest that elevated extracellular levels of dopamine within the
      nucleus accumbens and a greater responsivity to enhancements in DA release by
      ethanol may be factors which contribute to high-alcohol preference. Furthermore,
      the data suggest that alcohol may be more reinforcing in animals that exhibit an
      enhanced dopaminergic response to the first ethanol exposure, and that this
      effect may subsequently be associated with high-alcohol-seeking behavior.

PMID- 11236834
TI  - An examination between single-parent family background and drunk driving in
      adulthood: findings from the Northern Finland 1966 Birth Cohort.
AB  - BACKGROUND: It has been suggested earlier that parental loss could be an
      important risk factor for alcoholism in adulthood. We explored the association
      between different types of childhood families with later alcohol-related problems
      of the offspring, in particular drunk driving. METHODS: We used a large,
      prospectively collected general population birth cohort database (n = 10,934),
      the Northern Finland 1966 Birth Cohort. Linked with the National crime register,
      it provided information on drunk driving offenses known to the police that
      involved persons 15 to 32 years of age (n = 432). Type of family was categorized
      into five subgroups: two-parent family and four types of single-parent families
      (single-parent all the time, single-parent at birth, parental death, parental
      divorce). The information about family type was obtained from questionnaires
      given to the mothers during mid-pregnancy and at the time of the 14-year follow
      up. RESULTS: Single-parent family during childhood significantly increased the
      risk of drunk driving in adulthood among both males and females. Males who were
      born in single-mother families were at the highest risk of drunk driving offenses
      in adulthood (adjusted OR 2.4; 95% CI 1.4-4.2). The association between single
      parent family and drunk driving among males was seen in all types of single
      parent families except for parental death. CONCLUSIONS: Results suggest that
      growing up in a single-parent family is a potentially powerful predictor of adult
      alcohol-related problems, i.e., early-onset, late-onset, and recidivistic drunk
      driving.

PMID- 11236835
TI  - Concurrent alcoholism and social anxiety disorder: a first step toward developing
      effective treatments.
AB  - BACKGROUND: Social anxiety disorder (also called social phobia) is an anxiety
      disorder in which affected individuals fear the scrutiny of others. Clinical
      reports suggest that individuals with social anxiety disorder often use alcohol
      to alleviate anxiety symptoms, a practice that leads to alcohol abuse and/or
      dependence in approximately 20% of affected individuals. The present study
      investigated whether simultaneous treatment of social phobia and alcoholism,
      compared with treatment of alcoholism alone, improved alcohol use and social
      anxiety for clients with dual diagnoses of social anxiety disorder and alcohol
      dependence. METHODS: The design was a two-group, randomized clinical trial that
      used 12 weeks of individual cognitive behavioral therapy for alcoholism only (n =
      44) or concurrent treatment for both alcohol and social anxiety problems (n =
      49). Outcome data were collected at the end of 12 weeks of treatment and at 3
      months after the end of treatment. RESULTS: Results with intent-to-treat analyses
      showed that both groups improved on alcohol-related outcomes and social anxiety
      after treatment. With baseline scores covaried, there was a significant effect of
      treatment group on several drinking measures. Counter to the hypothesis, the
      group treated for both alcohol and social anxiety problems had worse outcomes on
      three of the four alcohol use indices. No treatment group effects were observed
      on social anxiety indices. CONCLUSIONS: Implications for the staging of
      treatments for coexisting social phobia and alcoholism are discussed, as well as
      ways that modality of treatments might impact outcomes.

PMID- 11236836
TI  - Genetic determinants of alcohol addiction and metabolism: a survey in Italy.
AB  - BACKGROUND: Although multiple genes are involved in alcoholism and can contribute
      differently to the risk of dependence and liver damage, no studies have
      investigated susceptibility to addiction in combination with susceptibility to
      liver damage due to differences in ethanol metabolism. METHODS: We evaluated the
      role of three polymorphic genes related to alcohol metabolism (CYP2E1) and,
      possibly, dependence (DRD2 and SLC6A4 promoter) in a series of 60 alcoholics
      admitted to a specialized referral center in Florence, Italy. Eighteen had a
      diagnosis of liver cirrhosis. A control series of 64 blood donors were identified
      at the same hospital. Genotyping was done by polymerase chain reaction
      restriction fragment length polymorphism methods. RESULTS: No difference was
      found in the frequency of the CYP2E1 Rsal c2 allele (2.5% among alcoholics and
      4.7% among controls) and the DraI C allele (6.7% and 10.1%). Similarly, no
      difference was found in the frequency of the DRD2 A1 allele (15.8% and 13.3%) and
      the B1 allele (10.8% and 8.6%). The proportion of controls with a combined B1
      genotype (B1/B1 or B1/B2) was significantly associated with smoking (p = 0.03).
      The distribution of the S and L allele of the SLC6A4 gene was similar in the two
      groups, with 15% and 14%, respectively, homozygous S/S carriers. A significant
      association, however, emerged in the group of alcoholics, with a five times
      higher risk for S/S carriers of developing cirrhosis (p < 0.05). This association
      with liver persisted even after exclusion of the subgrouped of 10 hepatitis C
      virus positive alcoholics. CONCLUSIONS: Overall, our results provided no evidence
      of an increased susceptibility to develop alcoholism that was associated with the
      three genotypes investigated, either alone or in combination. An increased risk
      of developing liver cirrhosis for S/S homozygous carriers among alcohol-dependent
      patients was observed for the first time.

PMID- 11236837
TI  - Identification of heavy drinkers by using the early detection of alcohol
      consumption score.
AB  - BACKGROUND: The objective of this study was to evaluate the use of routine blood
      chemistry and hematology tests to detect heavy drinkers among ambulatory
      subjects. Heavy drinkers were defined as subjects who consumed an average of four
      or more standard drinks per day if male and an average of three or more standard
      drinks per day if female, for at least 1 month before sample collection (1
      standard drink = 15 ml of absolute ethanol). METHODS: A routine blood chemistry
      panel and the demographic factors of age, sex, and ethnicity were evaluated by
      using linear discriminant function (LDF) analysis to classify subjects as heavy
      drinkers or light drinkers. The classification was validated by comparison with
      drinking patterns established by standardized questionnaire and interview.
      Subjects (n = 807) were males and females with known drinking patterns recruited
      from 25 centers that included detoxification and rehabilitation institutions,
      churches, and community groups in the Milwaukee and Boston areas. RESULTS: With
      LDF, 88% of the heavy drinkers and 92% of the light drinkers were correctly
      identified by the Early Detection of Alcohol Consumption test. The LDF performed
      the best when used to identify heavy drinking in ages 40 and above, a group that
      showed 84% (120 of 143) sensitivity at 97% (152 of 157) specificity. Performance
      in females showed 73% (76 of 104) sensitivity at 94% (129 of 137) specificity,
      rates higher than obtained with any single biochemical marker previously
      examined. Receiver operating characteristic plot analysis showed areas under the
      curve of 0.94 for females and 0.95 for males (p < 0.0001). CONCLUSIONS: The Early
      Detection of Alcohol Consumption score is a practical laboratory screen for
      detecting heavy drinking based on blood constituents ordered routinely in
      clinical settings.

PMID- 11236838
TI  - fMRI measurement of brain dysfunction in alcohol-dependent young women.
AB  - BACKGROUND: Studies of brain functioning in alcohol-dependent adults have
      produced varied results but generally suggest that alcohol affects brain
      functioning and that relatively short durations of heavy drinking may adversely
      affect women. It remains unclear when in the course of alcohol dependency and at
      which developmental stage these brain changes emerge. Our neuropsychological
      studies have indicated that drinking-related neurocognitive effects occur as
      early as adolescence (Brown et al., 2000; Tapert & Brown, 1999). This study seeks
      to characterize brain regions that subserve the affected neurocognitive
      functions. METHODS: Alcohol-dependent young women (n = 10) were recruited from a
      longitudinal study of alcohol- and drug-abusing youth, all of whom met criteria
      for alcohol dependence. Control participants (n = 10) had no history of alcohol
      or drug problems and were comparable with alcohol-dependent participants on age
      (18-25 years), family history of alcohol use disorders, and education. After a
      minimum of 72 hr of abstinence, functional magnetic resonance imaging,
      neuropsychological, alcohol/drug involvement, and mood data were collected.
      Participants performed spatial working memory and vigilance tasks during
      functional magnetic resonance imaging acquisition to probe brain response.
      RESULTS: Alcohol-dependent women demonstrated significantly less blood oxygen
      level-dependent response than controls during the spatial working memory task in
      the right superior and inferior parietal, right middle frontal, right
      postcentral, and left superior frontal cortex, after controlling for the baseline
      vigilance response. CONCLUSIONS: Working memory produces a larger neuronal
      response in some cortical regions than vigilance. Alcohol-dependent women showed
      less differential response to working memory than controls in frontal and
      parietal regions, especially in the right hemisphere. Heavy, chronic drinking
      appears to produce adverse neural effects that are detectable by functional
      magnetic resonance imaging.

PMID- 11236839
TI  - Coronary artery disease modifies left ventricular remodelling due to heavy
      alcohol consumption.
AB  - BACKGROUND: Coronary artery disease (CAD) and excessive alcohol use can both
      damage the myocardium. Their combined effect on the heart muscle has not been
      characterized. We set out to assess whether the presence of CAD modifies the
      effects of chronic alcohol consumption on the left ventricular (LV) structure in
      middle-aged men. METHODS: A postmortem examination was performed on 700 Finnish
      men (age range, 33-70 years) who experienced a sudden, nonhospital death. A
      coronary arteriography and measurement of the LV wall thickness, cavity area, and
      ratio by planimetry of transversal ventricular slices were done at the autopsy.
      The men were grouped by the most severe coronary artery diameter stenosis (<30%,
      30-60%, >60%) and by daily alcohol dose (<12 g, 12-72 g, 72-180 g, >180 g)
      estimated by a structured interview of their lifetime partner. RESULTS: Analysis
      by ANCOVA, adjusted for age, body size, smoking, hypertension, and diabetes,
      showed a statistically significant interaction between the effects of coronary
      artery stenosis and daily alcohol dose on the LV cavity area (p = 0.037) and on
      the LV wall thickness/cavity area ratio (p = 0.018). In the group with <30%
      stenosis, the LV wall thickness/cavity area ratio (mean +/- SEM) increased from
      1.6 +/- 0.2 mm/cm2 in men drinking <12 g/day to 6.2 +/- 1.4 mm/cm2 in men
      drinking 72-180 g/day (p = 0.021). A similar trend was seen in men with 30-60%
      coronary stenosis (p = 0.32). By contrast, in men with >60% coronary stenosis,
      the LV wall thickness/cavity area ratio decreased with increasing daily alcohol
      use from 2.2 +/- 0.3 to 1.4 +/- 0.1 mm/cm2 (p = 0.27). CONCLUSIONS: CAD modulates
      the effects of alcohol on the heart muscle. Heavy drinking results in concentric
      LV remodelling in men with no or only mild coronary artery stenoses whereas an
      opposite trend is seen in men with severe coronary artery obstructions. The
      mechanism of the interaction remains unknown.

PMID- 11236840
TI  - Azide inhibits human cytochrome P -4502E1, 1A2, and 3A4.
AB  - BACKGROUND: Recently, we showed that, in addition to cytochrome P-4502E1
      (CYP2E1), CYP1A2 and CYP3A4 also contribute to the microsomal ethanol oxidizing
      system (MEOS). When MEOS activity is measured, sodium azide commonly is used to
      block the contaminating catalase. However, although CYP2E1 is considered
      insensitive to azide, its effect on the other P-450s is unknown. Therefore, the
      aim of the present study was to determine the effect of azide on human
      recombinant and hepatic CYP2E1, CYP1A2, and CYP3A4. METHODS AND RESULTS:
      Concentrations of sodium azide as low as 0.1 mM markedly inhibited the specific
      ethanol oxidation (mean +/- SEM) by recombinant CYP1A2 and CYP3A4 expressed in
      HepG2 cells (to 16 +/- 1% and 22 +/- 2% of control without azide, respectively; p
      < 0.01). By contrast, the specific activity of CYP2E1 was only slightly (and not
      significantly) inhibited at this azide concentration (to 79 +/- 12% of control).
      Similarly, in human liver microsomes (n = 6), 0.1 mM azide strongly inhibited
      CYP1A2-dependent (to 25 +/- 2%) and CYP3A4-dependent (to 15 +/- 2%) ethanol
      oxidation, whereas CYP2E1 was inhibited only at 10 mM azide (to 60 +/- 10%).
      Azide also strongly affected the apparent kinetic values of all three isoenzymes.
      Furthermore, azide inhibited the specific monooxygenase activities, both by
      recombinant and microsomal P-450s. CYP2E1-specific p-nitrophenol hydroxylation
      was the most sensitive to azide, whereas CYP1A2-dependent 7-methoxyresorufin O
      dealkylation was only slightly inhibited. Judging from its effect on p
      nitrophenol hydroxylation by human liver microsomes, the inhibition of azide was
      competitive (Ki 0.09 mM). CONCLUSIONS: Sodium azide at a concentration as low as
      0.1 mM inhibited ethanol oxidation by CYP1A2 and CYP3A4. With CYP2E1, although
      oxidation of 50 mM ethanol was not inhibited by 0.1 mM azide, higher azide
      concentrations were inhibitory and 0.1 mM azide seemed to affect the kinetics of
      ethanol oxidation by CYP2E1. Therefore, azide should be avoided when measuring
      the MEOS activity because it may lead to underestimation, especially of CYP1A2-
      and CYP3A4-dependent ethanol oxidation.

PMID- 11236841
TI  - Endotoxin, endotoxin-neutralizing-capacity, sCD14, sICAM-1, and cytokines in
      patients with various degrees of alcoholic liver disease.
AB  - BACKGROUND: Chronic alcohol ingestion leads to endotoxemia which is believed to
      play an important role in the pathogenesis of alcoholic liver disease (ALD). The
      purpose of this study was to determine if chronic ethanol consumption, in
      addition to affecting plasma endotoxin and cytokines, also affects the endotoxin
      neutralizing capacity (ENC), sCD14, and sICAM-1, in patients with ALD. A second
      aim was to identify correlations between these latter parameters, endotoxin, and
      cytokines, especially IL-10. METHODS: Hospitalized patients with various degrees
      of ALD (n = 59), and 20 healthy volunteers were studied. Plasma endotoxin and ENC
      were determined using our kinetic Limulus amebocyte lysate test. Cytokines,
      sCD14, and sICAM-1 were measured by enzyme-linked immunosorbent assay. RESULTS:
      Patients with ALD exhibited a mild endotoxemia (p < 0.01) and a marked decrease
      in ENC (p < 0.0002). TNF-alpha (p < 0.05), IL-6 (p < 0.0001), sICAM (p < 0.005),
      and sCD14 (p < 0.0005) were significantly elevated in all patients with ALD, and
      IL-10 (p < 0.05) in patients with cirrhotic ALD. With the exception of IL-10, the
      cytokines correlated with each other and with sICAM-1. No correlations occurred
      between endotoxin, ENC, and sCD14, and between these and the cytokines and sICAM
      1. Elevated levels of endotoxin correlate with acute excessive alcohol ingestion.
      No gender differences were observed. CONCLUSIONS: Acute alcohol intoxication
      rather than severe ALD results in significant endotoxemia. The limited capacity
      of plasma to neutralize endotoxin in liver injury seems to be an important factor
      in ALD which may be responsible for the release of endotoxin-induced mediators,
      such as cytokines, as well as s-ICAM-1, that are relevant in the pathogenesis of
      ALD.

PMID- 11236842
TI  - Third trimester binge ethanol exposure results in fetal hypercapnea and acidemia
      but not hypoxemia in pregnant sheep.
AB  - BACKGROUND: The mechanisms by which maternal ethanol abuse during pregnancy
      causes neurodevelopmental injury in the fetus are not well understood. The
      purpose of this study was to use a chronically instrumented fetal sheep model
      system to determine if a binge pattern of ethanol exposure administered
      throughout the third trimester reduced fetal arterial partial pressure of oxygen
      (PaO2); a positive finding would support the hypothesis that fetal hypoxemia may
      play a role in mediating ethanol-related birth defects. METHODS: Pregnant ewes
      received saline or 0.75, 1.25, 1.5, or 1.75 g/kg of ethanol intravenously over 1
      hr beginning on day 109 of gestation (term = 145 days) for 3 consecutive days per
      week followed by 4 days without exposure. The fetuses were surgically
      instrumented on day 113, and experiments were performed on days 118 or 132, the
      6th and the 12th ethanol exposure, respectively. RESULTS: Ethanol infusions
      resulted in peak blood ethanol concentrations of 80.8 +/- 6.5, 182.5 +/- 13.5,
      224.4 +/- 13.9, and 260.6 +/- 20.0 mg/dl +/- SEM (maternal) and 70.0 +/- 5.9,
      149.7 +/- 9.0, 216.9 +/- 14.0, and 233.3 +/- 19.8 mg/dl +/- SEM (fetal) in
      response to the 0.75, 1.25, 1.5, and 1.75 g/kg doses, respectively. Maternal and
      fetal heart rate and maternal blood pressure increased whereas fetal blood
      pressure decreased in a dose-dependent manner in response to ethanol infusions.
      Maternal and fetal arterial pH decreased and arterial partial pressures of carbon
      dioxide increased in response to ethanol infusions. Maternal PaO2 decreased
      whereas fetal PaO2 did not change in response to ethanol infusions. CONCLUSIONS:
      A binge ethanol exposure paradigm, three consecutive days per week throughout the
      third trimester at ethanol doses that created blood ethanol concentrations
      commonly achieved by human ethanol abusers, resulted in changes in maternal and
      fetal heart rate, changes in blood pressure, hypercapnea, acidemia, and maternal,
      but not fetal, hypoxemia. We conclude that in an ovine model system, ethanol
      doses that create blood ethanol concentrations as high as 260 mg/dl do not result
      in fetal hypoxemia. Remaining issues to address with this model system are
      whether neurodevelopmental injuries that are associated with maternal ethanol
      abuse are mediated by a reduction in fetal cerebral blood flow, fetal
      hypercapnea, or acidemia.

PMID- 11236843
TI  - Effects of SR141716A on ethanol and sucrose self-administration.
AB  - BACKGROUND: Previous studies have demonstrated that administration of central
      cannabinoid receptor (CB1) ligands can produce marked effects on ingestive
      behaviors. However, the possible relationship to ethanol self-administration has
      not been fully examined. The present series of experiments was designed to
      characterize further the role of CB1 receptors in appetitive and consummatory
      behaviors related to sucrose and ethanol. METHODS: To determine the relative
      contribution of CB1 receptors to ethanol seeking and consumption, a series of
      experiments was designed using the sipper-tube model. In this paradigm, the
      appetitive and consummatory phases of ethanol and sucrose self-administration are
      separated. In the appetitive phase, animals are required to complete a response
      requirement (16 lever presses) within 20 min. If the requirement is successfully
      completed, access to a sipper tube containing either sucrose or ethanol
      (consummatory phase) is made available for 20 min. RESULTS: In the ethanol
      condition, the CB1 receptor antagonist SR141716A (0.3-3.0 mg/kg, ip) produced
      dose-related decreases in the probability of response requirement completion
      without significantly affecting latency to first lever press or overall lever
      press rate. In the sucrose condition, SR141716A (0.3-3.0 mg/kg, ip) increased
      first lever press latency without affecting lever press rate. In the consummatory
      phase, SR141716A (0.3-3.0 mg/kg, ip) administration markedly decreased total
      intake and the total number of licks for both ethanol and sucrose. CONCLUSIONS:
      These data indicate that CB1 receptors are involved in mediating both appetitive
      and consummatory aspects of ingestive behaviors related to sucrose and ethanol.

PMID- 11236844
TI  - Identifying maternal self-reported alcohol use associated with fetal alcohol
      spectrum disorders.
AB  - BACKGROUND: The incidence of Fetal Alcohol Syndrome (FAS) has been estimated at 1
      to 3 per 1,000 live births. Fetal Alcohol Spectrum Disorders (FASD) (which
      include FAS) are estimated to occur in about 1 in 100 births. Cessation of
      drinking during pregnancy can improve the outcome even if the unborn child is
      already affected. For individuals born with FASD, an early diagnosis appears to
      be a protective factor against secondary disabilities. A quick screening tool to
      identify newborn children at risk has been elusive. METHODS: A simple descriptive
      presentation is offered that shows where 36 individuals with FASD were found from
      among the many patterns and amounts of prenatal alcohol use that were reported by
      a sample of 1,439 pregnant women whose offspring were later examined within the
      first 7 years of life. RESULTS: Individuals with FASD (i.e., those with FAS,
      fetal alcohol effects, alcohol-related neurodevelopmental disorder ) were found
      within two aggregates of alcohol scores that together recommend a set of three to
      four alcohol questions. Within this derivation sample, one scoring of the
      questions yields almost 78% sensitivity and 97% specificity for FASD. Another
      scoring of the same instrument yields 100% sensitivity with 90% specificity.
      CONCLUSIONS: These new data may facilitate early identification of offspring who
      may be most in need of early intervention, namely those born with FASD.

PMID- 11236845
TI  - Use of genetic analyses to refine phenotypes related to alcohol tolerance and
      dependence.
AB  - Various explanations for the dependence on alcohol are attributed to the
      development of tolerance to some of alcohol's effects, alterations in sensitivity
      to its rewarding effects, and unknown pathologic consequences of repeated
      exposure. All these aspects of dependence have been modeled in laboratory
      rodents, and these studies have consistently shown a significant influence of
      genetics. Genetic mapping studies have identified the genomic location of the
      specific genes for some of these contributing phenotypes. In addition, studies
      have shown that some genes in mice seem to affect both alcohol self
      administration and alcohol withdrawal severity: genetic predisposition to high
      levels of drinking covaries with genetic predisposition to low withdrawal
      severity, and vice versa. Finally, the role of genetic background on which genes
      are expressed is important, as are the specifics of the environment in which
      genetically defined animals are tested. Understanding dependence will require
      disentangling the multiple interactions of many contributing phenotypes, and
      genetic analyses are proving very helpful. However, rigorous understanding of
      both gene-gene and gene-environment interactions will be required to interpret
      genetic experiments clearly.

PMID- 11236846
TI  - Approaches to understanding the neurobiological regulation of ethanol self
      administration: a young investigators forum.
AB  - The article represents the proceedings of a symposium at the 2000 RSA Meeting in
      Denver, Colorado. The co-chairs were Cristine L. Czachowski and Craig J.
      Slawecki. The presentations were (1) Behavioral assessment of ethanol seeking and
      self-administration, by Cristine L. Czachowski; (2) Electrophysiological measures
      of ethanol preference and reinforcing efficacy, by Craig J. Slawecki; (3) Genetic
      differences in locomotor sensitization and reward phenotypes associated with
      bidirectional selection for alcohol preference in mice, by Nicholas J. Grahame;
      (4) Transgenic and knockout mouse models: Powerful tools for investigating the
      neurobiology of alcoholism, by Todd E. Thiele; and (5) Neurochemical
      characteristics that may predict ethanol preference in selected P and NP rats: A
      quantitative microdialysis study, by Simon N. Katner.

PMID- 11236847
TI  - The role of craving in alcohol use, dependence, and treatment.
AB  - This article represents the proceedings of a symposium at the 2000 RSA Meeting in
      Denver, Colorado. The organizer and chair was Barbara A. Flannery, and the co
      chairs were Barbara A. Flannery and Helen Pettinati. The presentations were (1)
      Animal models of alcohol craving and relapse, by Amanda Roberts; (2) Real-time
      field assessment of alcohol craving, by Ned Cooney; (3) Medications and alcohol
      craving, by Robert Swift; (4) The assessment of craving: Insights from the clinic
      and clinical laboratory studies, by Raymond Anton; (5) A comparison of three
      alcohol craving questionnaires, by Barbara Flannery; (6) and Assessing
      posttreatment urge to drink, by Damaris Rohsenow.

PMID- 11236848
TI  - Innovative technologies for the diagnosis of alcohol abuse and monitoring
      abstinence.
AB  - This article summarizes the proceedings of a workshop presented at the 2000 RSA
      Meeting in Denver, Colorado. The aim of this workshop was to discuss the basic
      methodologies, diagnostic performance, and clinical utility of three
      technologies: carbohydrate-deficient transferrin, the "Early Detection of Alcohol
      Consumption" score, and whole blood associated acetaldehyde. Each method adopts a
      different strategy to identify heavy alcohol consumption and offers a unique
      approach to determine alcohol abstinence and relapses. Appropriate application of
      these technologies can lead to early intervention for alcohol problems before
      significant tissue damage occurs. To date these methodologies have yet to be
      formally contrasted and compared. Sensitivity, specificity, predictive value,
      availability, ease of use, and interpretation of tests results are important
      aspects to consider when selecting the most appropriate and cost-effective
      system. Critical evaluation of these methodologies can enable research and
      clinical laboratories to choose the system that best meets their particular needs
      in terms of assay feasibility, budget, and goals.

PMID- 11236849
TI  - Neurotoxicity and neurocognitive impairments with alcohol and drug-use disorders:
      potential roles in addiction and recovery.
AB  - This article represents the proceedings of a symposium at the 2000 RSA Meeting in
      Denver, Colorado. The organisers/chairs were Stephen C. Bowden and Fulton T.
      Crews. The presentations were (1) Age, genetic and other factors that increase
      risk of alcoholism also increase alcohol-induced neurotoxicity, by Fulton T.
      Crews; (2) A neurocognitive moderation model of addictions treatment response, by
      Marsha E. Bates; (3) The relationship of neurocognitive impairment and
      longitudinal treatment outcome among substance-abusing patients, by William Fals
      Stewart; and (4) Treatment of cognition in detoxifying alcohol-dependent
      participants, by Margaret L. Ambrose.

PMID- 11236851
TI  - Response shift in quality of life measurement in early-stage breast cancer
      patients undergoing radiotherapy.
AB  - In medicine, response shift refers to a change--as a result of an event such as a
      therapy--in the meaning of one's self-evaluation of quality of life. Due to
      response shift, estimates of side effects of radiotherapy may be attenuated if
      patients adapt to treatment toxicities. The purpose of our study was to assess to
      what extent two components of response shift, scale recalibration and changes in
      values, occur in early-stage breast cancer patients undergoing radiotherapy and
      to examine what the implications would be for treatment evaluation. In the week
      before start of post-operative radiotherapy, 46 patients filled out a
      questionnaire consisting of quality of life items of the SF-36 and the Rotterdam
      symptom checklist (RSCL) (pretest). During radiotherapy, patients were asked to
      fill out the questionnaire twice: a posttest (quality of life at that moment) and
      a thentest (quality of life before treatment, retrospectively), supposedly using
      the same internal standard. Changes in values were studied by asking the patients
      on the two occasions to rate the importance of seven attributes representing
      various domains of quality of life. Patients were also asked whether their
      quality of life with respect to the measured aspects had changed since the
      pretest (subjective transition scores). Significant scale recalibration effects
      were observed in the areas of fatigue and overall quality of life. When the
      groups were divided according to their subjective transition scores, significant
      scale recalibration effects were found in case of worsened quality of life for
      fatigue and overall quality of life, and in case of improved quality of life for
      fatigue and psychological well-being. The mean importance ratings remained fairly
      stable over time, except for 'skin reactions', which obtained less importance at
      the end of radiotherapy than before. In conclusion, effects of scale
      recalibration were observed that would have significantly affected quality of
      life evaluations, in that the impact of radiotherapy on fatigue and overall
      quality of life would have been underestimated. Changes in internal values were
      observed only for 'skin reactions'.

PMID- 11236850
TI  - Comparison of the Health Utilities Index Mark 3 (HUI3) and the EuroQol EQ-5D in
      patients treated for intermittent claudication.
AB  - The Health Utilities Index Mark 3 (HUI3) and the EuroQol EQ-5D (EQ-5D) were
      compared to each other and to other quality-of-life (QoL) measures in patients
      treated for intermittent claudication. A total of 88 patients with intermittent
      claudication completed the HUI3, EQ-5D, RAND 36-Item Health Survey 1.0, time
      tradeoff, standard gamble, and rating scale before revascularization and at
      follow-up at 1 month, 3 months, and 1 year. The effect of treatment on the HUI3
      and EQ-5D dimensions and the overall scores, calculated using published formulas
      based on societal preferences, were compared. After 1 month of treatment, the
      majority of patients showed improvement on the HUI3 dimensions ambulation and
      pain and on the EQ-5D dimensions mobility, usual activities, and pain/discomfort.
      The mean HUI3 score was significantly higher than the mean EQ-5D score (0.66 and
      0.57, respectively, p < 0.01) before treatment. After treatment, however, they
      were not significantly different from each other (e.g., 12 months after
      treatment: 0.77 and 0.75, respectively (p > 0.05). After 1 month, the scores did
      not change significantly over time (p > 0.05). The intraclass correlation
      coefficient between changes over time in the HUI3 and EQ-5D scores was 0.30, with
      other health-related quality-of-life (HRQoL) measures the correlations for HUI3
      and EQ-5D were very similar. In conclusion, both the HUI3 and EQ-5D demonstrated
      an effect of treatment in patients with intermittent claudication; in addition,
      they showed similar relationships with other (HRQoL) measures. To demonstrate the
      effect of revascularization in patients with intermittent claudication, however,
      clinicians and researchers should be aware of the differences in the mean HUI3
      and EQ-5D scores.

PMID- 11236852
TI  - Norm values for the Generic Children's Quality of Life Measure (GCQ) from a large
      school-based sample.
AB  - This study aimed to assess the quality of life of a population sample of
      schoolchildren. The Generic Children's Quality of Life Measure (GCQ) has been
      developed to allow comparison between chronically ill children and the general
      child population. The measure assesses how the child views his or her life and
      also how they would like it to be. Quality of life is measured as the discrepancy
      between the two viewpoints. This large community-based survey aimed to establish
      GCQ norm values for children aged 6-14 years. The children were from a sample of
      schools stratified by geographical location and social need: rural affluent,
      rural low affluence, urban affluent and urban low affluence. 720 completed
      questionnaires were analysed. The scores were normally distributed with a wide
      range. The GCQ showed an acceptable reliability with a Cronbach's alpha of 0.75.
      The quality of life score was not correlated with age (r = -0.02, p = 0.64) nor
      with the deprivation score of the area in which the children lived (r = -0.026, p
      = 0.49). There were no significant differences between the scores by gender (p =
      0.22) nor by rural/urban location (p = 0.60). Normative values were established.
      The GCQ is suitable for using with children over a large age range (6-14 years)
      without the scores being confounded by the age, gender, affluence or geographical
      location.

PMID- 11236854
TI  - Parental perception of the quality of life among children with epilepsy or
      diabetes with a new assessment questionnaire.
AB  - This paper describes the evaluation of a newly designed questionnaire to assess
      the quality of life among children with epilepsy or diabetes. Factor analysis
      identified one factor, the impact on the parents and the family, which was
      responsible for over a third of the variance in the two illness groups. Two other
      factors, impact on development and impact on health, were also found in the
      epilepsy group. The questionnaire discriminates well between children with
      epilepsy or diabetes, showing that the former is more affected than the latter.
      Children with more severe epilepsy are seen by parents to have a worse quality of
      life than children whose epilepsy is well controlled.

PMID- 11236853
TI  - Which source should we use to measure quality of life in children with asthma:
      the children themselves or their parents?
AB  - This study compares the reproducibility, construct validity and responsiveness of
      self-report and parent-report quality of life questionnaires How Are You (HAY)
      for 8-12-year-old children with asthma. A total of 228 Dutch children with asthma
      and their parents completed the HAY and daily recorded the child's asthma
      symptoms in a diary. Additionally 296 age- and -gender matched healthy children
      and their parents completed the generic part of the HAY. Reproducibility and
      responsiveness were examined in a sub-group of 80 children with asthma. In this
      group, three measurements were carried out, at baseline, after one week and once
      during the following 6 month when the clinical asthma status had changed. The
      within-subject standard deviations (SD) of three dimensions (physical activities,
      social activities, self-management) differed significantly (p < 0.05) in favour
      of the parent-version, indicating that the reproducibility of the parent version
      was better than that of the child version. The mean score-differences between
      children with asthma and healthy children as reported by parents did not
      significantly differ from those reported by children, except for cognitive
      activities (e.g. be able to concentrate on school work). The mean differences
      with regard to children with a different actual asthma status (symptom analysis),
      as reported by both informants, did not differ. Compared to the child-version,
      the parent-version showed greater ability to detect changes in children's quality
      of life over time for all but one dimension, indicating better responsiveness.
      The results indicate that in discriminative studies child and parents reports can
      be substituted on a group-level. In longitudinal studies data have to be obtained
      from parents. Consequently, caregivers collecting quality of life data for
      longitudinal purposes in daily practice should collect these data simply from
      parents.

PMID- 11236855
TI  - Assessing quality of life in men with clinically localized prostate cancer:
      development of a new instrument for use in multiple settings.
AB  - BACKGROUND: Quality of life in prostate cancer patients with clinically localized
      disease has become the focus of increasing attention over the past decade.
      However, few instruments have been developed and validated to assess quality of
      life specifically in this patient population. OBJECTIVE: The purpose of this
      investigation was to create a comprehensive, multi-scale quality of life
      instrument that can be tailored to the needs of the clinician/investigator in
      multiple settings. DESIGN, SUBJECTS, AND MEASURES: Patients diagnosed with
      clinically localized prostate cancer were mailed a questionnaire consisting of
      new and previously validated quality of life items and ancillary scales. Data
      from returned questionnaires were analyzed and used to create a multiscale
      instrument that assesses the effects of treatment and disease on urinary, sexual,
      and bowel domains, supplemented by a scale assessing anxiety over disease
      course/effectiveness of treatment. The instrument was then mailed to a second
      sample of prostate cancer patients once and then again two weeks later to assess
      test retest reliability. To assess feasibility in clinical settings, the
      instrument was self-administered to a third patient sample during a urology
      clinic visit. RESULTS: All scales exhibited good internal consistency and test
      retest reliability, convergent and discriminant validity, and significant
      correlations with disease specific, generic health-related, and global measures
      of quality of life. Men with greater physiologic impairment reported more
      limitations in role activities and more bother. Scales were also able to
      differentiate patients undergoing different therapies. All scales exhibited
      negligible correlations with a measure of socially desirable responding.
      Additionally, the instrument proved feasible when used as a self-administered
      questionnaire in a clinical setting. CONCLUSIONS: The current instrument
      possesses brief multi-item scales that can be successfully self-administered in
      multiple settings. The instrument is flexible, relatively quick, psychometrically
      reliable and valid, and permits a more comprehensive assessment of patients'
      quality of life.

PMID- 11236856
TI  - The health-related quality of life in eating disorders.
AB  - OBJECTIVE: This study investigated the perception of health-related quality of
      life (HRQoL) in ambulatory patients with eating disorders in relation to the
      severity of eating symptomatology and psychological comorbidity. METHODS: One
      hundred ninety-seven study patients were consecutively recruited at the Eating
      Disorders Outpatient Clinic. Short Form-36 items (SF-36), a generic HRQoL
      questionnaire, the Eating Attitudes Test (EAT-40), and the Hospital Anxiety and
      Depression Scale (HAD) were used to measure different aspects of HRQoL. The
      results of the SF-36 were compared with the norms of the Spanish general
      population for women 18-34 years of age. RESULTS: Patients with eating disorders
      were more dysfunctional in all areas of the SF-36 compared with women in the
      general population. There were no differences among the eating disorder
      diagnostic groups. Higher scores on the EAT-40 and the HAD were associated with a
      perception of greater impairment on all SF-36 subscales. CONCLUSION: The
      evaluation of HRQoL in these patients confirms the impact of these disorders on
      daily life in areas not directly related to eating disorders. The SF-36 is useful
      for discriminating among different levels of severity of eating disorders and
      other psychological comorbidities of these patients.

PMID- 11236857
TI  - Psychometric evaluation of a Chinese (Taiwanese) version of the SF-36 health
      survey amongst middle-aged women from a rural community.
AB  - To test the psychometric properties of the Chinese (Taiwanese) version of the
      short form 36 health survey (SF-36), 1,439 women, aged 40-54 years and living in
      Kinmen (a Taiwanese island reflecting a predominantly rural community) were
      recruited to participate in this survey. The rate of unavailable data points for
      the 36 tested items remained consistently low, and item-discriminate validity was
      high (95%) for all subscales. Cronbach's alpha coefficient remained above the
      0.70 threshold criterion for all scales except for social functioning and bodily
      pain. Principal components analysis supported the two major dimensions of health,
      physical and mental, in the internal structure of the SF-36 scales, although the
      dimensions did not match the hypothesized association very well. Poorer health
      profiles were associated with physical and mental conditions. The mental health
      subscores in the SF-36 test correlated highly with the associated hospital
      anxiety and depression score (Spearman rank correlation coefficient = -0.62). In
      conclusion, the reliability and validity tests performed on the data collected
      support the cross-cultural application of the Chinese (Taiwanese) version of the
      SF-36 test.

PMID- 11236858
TI  - An isonymic study of the population structure of early Kings County, NY.
AB  - Isonymy has proven a useful method for studying the genetic structure of
      historical populations. In the United States, the populations studied have been
      of predominantly British origin. Many of the early settlers in this country,
      however, came from different cultural backgrounds, which may have affected their
      settlement patterns and genetic structure. The first European settlers of Kings
      County, New York, were Dutch, and Dutch was still spoken there in the 19th
      century. In the early Colonial period, it was an isolated agricultural area, but
      it was increasingly drawn into the larger metropolis of New York City, a process
      that culminated at the end of the 19th century. This paper uses census data from
      1698, 1738, 1790, and 1810 to assess synchronic and diachronic isonymy patterns
      within the county. These censuses subdivide the county into six towns, five
      founded by the Dutch (Brooklyn, Bushwick, Flatbush, Flatlands, and New Utrecht)
      and one by the English (Gravesend). All were founded at least a generation before
      1698. Values of Iii, FST, and RST increased from 1698 to 1738, a period when
      Kings County received few immigrants, and decreased thereafter as the influence
      of the metropolis grew. Most new immigrants settled in Brooklyn, so the lowest
      levels of isonymy occurred there [Iii (1810) = 0.0029]. The highest levels
      occurred in Flatlands [Iii (1738) = 0.0838]. FST increased from 0.0050 to 0.0076,
      and then fell to 0.0052 and 0.0032; RST was approximately two-thirds as high, at
      0.0033, 0.0053, 0.0033, and 0.0022. These values are more than twice as high as
      those reported from 19th-century Massachusetts or Pennsylvania, and are
      comparable to those found in rural European populations. The towns can be divided
      into two groups: Brooklyn, Bushwick, and Flatbush, with an average Iii of
      0.01570, and Flatlands, Gravesend, and New Utrecht, with an average value of
      0.03963. The three latter towns were geographically more distant from New York
      City and remained more isolated both culturally and biologically.

PMID- 11236859
TI  - Cytochrome P4501A1 polymorphisms in South American Indians.
AB  - A total of 131 individuals from five Brazilian Indian tribes were studied for two
      CYP1A1 gene polymorphisms. The presence of the *val allele at codon 462 varied
      from 54% in the Surui to 97% in the Xavante, while the presence of the MspI
      restriction site (*m2 allele) at position T6235C ranged from 72% in the Gaviao to
      95% in the Xavante. The haplotypes derived from these two sites showed a highly
      heterogeneous distribution among the five populations. The most common haplotype
      in South Amerindians was *val/*m2 (54% to 94%). This prevalence is the highest
      that has been observed in any world population.

PMID- 11236860
TI  - Diversity of two short tandem repeat loci (CD4 and F13A1) in three Brazilian
      ethnic groups.
AB  - Two microsatellites (CD4 and F13A1) were investigated in seven Brazilian
      populations: one group each of European- and African-derived subjects from Porto
      Alegre, southern Brazil, and five Amerindian tribes (three Tupi-Monde speaking
      [Gaviao, Surui, and Zoro], one Macro-Ge [Xavante], and one Carib [Wai-Wai]). For
      both markers, neo-Brazilians presented with a high diversity, but Amerindians
      showed a low level of variability. Genotype frequency distributions were
      heterogeneous among populations, the only exception being similar CD4 frequencies
      in Afro- and Euro-Brazilians. Gene diversity analysis revealed that most of the
      total variation is due to intrapopulational diversity in all populations. Because
      of the high information content of these markers in Afro- and Euro-Brazilians,
      these systems are most appropriate for forensic analyses. The comparison among
      Brazilian and other world populations revealed high similarity among populations
      of the same ethnic group, indicating a high discriminative power for these
      markers.

PMID- 11236861
TI  - Von Willebrand factor gene polymorphisms in three Brazilian ethnic groups.
AB  - Von Willebrand factor gene polymorphisms were studied in three Brazilian ethnic
      groups: Euro-Brazilians, Afro-Brazilians, and Amerindians. Six polymorphic sites
      were analyzed: RsaI (exon 18), NlaIV (exon 20), HphI, KpnI, D1472H, and V1565L
      (all four in exon 28). The allele frequencies were significantly different
      between Euro- and Afro-Brazilians for RsaI, HphI, D1472H, and V1565L, while in
      Amerindians NlaIV and HphI showed significant differences among tribes. This is
      the first report of these allele frequencies in Amerindians. Eighteen haplotypes
      were observed, and they showed significant differences between Euro- and Afro
      Brazilians, among Amerindian tribes, and among the three ethnic groups. These
      results furnish important background data for evolutionary and anthropological
      investigations; in addition, they will be useful for establishing the origin and
      molecular characterization of the different forms of von Willebrand disease, as
      well as for detecting carriers and offering genetic counseling to those with this
      condition.

PMID- 11236862
TI  - Mitochondrial DNA variant 11719G is a marker for the mtDNA haplogroup cluster HV.
AB  - Based on sequencing data and results obtained from applying a tailored mismatch
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      analysis, we report that the G allele of the mitochondrial DNA (mtDNA)
      polymorphism at nucleotide position 11719 is associated with the European mtDNA
      haplogroup cluster HV, and that 11719A is therefore the ancestral allele.

PMID- 11236863
TI  - Long DOP-PCR of rare archival anthropological samples.
AB  - The application of molecular DNA technologies to anthropological questions has
      meant that rare or archival samples of human remains, including blood, hair, and
      bone, can now be used as a source of material for genetic analysis. Often, these
      samples are irreplaceable, and/or yield very small quantities of DNA, so methods
      for preamplifying as much of the whole genome as possible would greatly enhance
      their usefulness. DOP-PCR (degenerate oligonucleotide-primed polymerase chain
      reaction) is an amplification method that uses a degenerate primer and very low
      initial annealing temperatures to amplify the whole genome. We adapted a
      published DOP-PCR protocol to long PCR enzyme and amplification conditions. The
      effectiveness of these modifications was tested by PCR amplification of DOP-PCR
      products at a mixture of genomic targets including 66 different microsatellites,
      11 Alu insertion polymorphisms, and variable-length segments of the human
      lipoprotein lipase gene (LPL). The selected microsatellite markers were chosen to
      represent every chromosome, with expected product sizes ranging from 150 base
      pairs to 8,000 base pairs in length, while the 22 Alu insertion polymorphisms
      were selected to reveal biases in the recovery of alleles of different sizes. To
      determine nucleotide sequence variation, 2 kilobases (kb) of the LPL gene in 30
      Mongolian individuals were sequenced. All gene-specific targets from DOP-PCR
      product template were amplified. No unexpected polymorphisms in the sequence
      results attributable to the DOP-PCR step were found, and 93% to 95% of Alu
      genotypes that have been amplified from total genomic DNA were replicated. The
      incorrect typings were all due to the preferential amplification of the shorter
      of two possible alleles in individuals heterozygous for an Alu insertion and were
      all correctly typed on subsequent reamplification of the gene-specific PCR
      products. This method of whole-genome amplification promises to be an efficient
      way to maximize the genetic use of rare anthropological samples.

PMID- 11236864
TI  - Genetic analysis of the Utah population: a comparison of STR and VNTR loci.
AB  - Genetic data are reported for nine short tandem repeat (STR) loci (D3S1358, vWA,
      FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, and D7S820) and six variable
      number of tandem repeat (VNTR) loci (D2S44, D10S28, D4S139, D1S7, D5S110, and
      D17S79) in samples of Utah African Americans, European Americans, and Hispanics.
      Little evidence of departures from Hardy-Weinberg equilibrium or gametic
      equilibrium was found in these populations. Because of their relatively higher
      mutation rates, the VNTR loci exhibited higher average heterozygosity and lower
      FST levels than did the STR loci. Genetic distance analysis showed congruence
      between the two types of systems, and a genetic distance analysis of the STR data
      showed that the three Utah populations are genetically similar to the same ethnic
      groups in other parts of the United States. In addition, this analysis showed
      that the African American population is the most genetically divergent, with
      greater similarity between the Hispanic and European American populations. This
      analysis demonstrates a high degree of consistency for population designations
      commonly used in forensic analysis.

PMID- 11236865
TI  - Clinal variation of YAP+ Y-chromosome frequencies in Western Iberia.
AB  - The potential of Y-chromosome biallelic marker haplotypes to infer population
      affiliations and structures was exploited to analyze four populations from the
      southwestern edge of Europe, namely north, central, and south Portugal and
      Galicia. Three markers subdividing the YAP+ lineage were analyzed: the YAP Alu
      element insertion itself and the SRY8299 and sY81 base substitutions; these
      respectively define three haplotypes known as 4, 21, and 8. Only haplotype 21 was
      detected presenting an increasing north-to-south frequency gradient, from 9.6%
      (Galicia) to 24.5% (South Portugal). This clinal distribution most likely
      reflects the genetic input associated with the Neolithic spread of agriculture,
      but we cannot exclude other movements as potential contributors to the
      distribution. In this context, it is interesting to note the consistency between
      the clinal variation and the population movement associated with Islamic rule in
      Iberia. The absence of haplotype 8, a marker of sub-Saharan populations, suggests
      that, despite the massive introductions of African slaves in historical times,
      there was little admixture between the African males and Western Iberian
      populations.

PMID- 11236866
TI  - Mitochondrial DNA variation in two South Siberian Aboriginal populations:
      implications for the genetic history of North Asia.
AB  - The mtDNAs of 76 individuals representing the aboriginal populations of South
      Siberia, the Tuvinians and Buryats, were subjected to restriction fragment length
      polymorphism (RFLP) analysis and control region hypervariable segment I (HVS-I)
      sequencing, and the resulting data were combined with those available for other
      Siberian and East Asian populations and subjected to statistical and phylogenetic
      analysis. This analysis showed that the majority of the Tuvinian and Buryat
      mtDNAs (94.4% and 92.5%, respectively) belong to haplogroups A, B, C, D, E, F,
      and M*, which are characteristic of Mongoloid populations. Furthermore, the
      Tuvinians and Buryats harbor four Asian- and Native American-specific haplogroups
      (A-D) with frequencies (72.2% and 55%, respectively) exceeding those reported
      previously for Mongolians, Chinese, and Tibetans. They represent, therefore, the
      populations that are most closely related to New World indigenous groups. Despite
      their geographical proximity, the Tuvinians and Buryats shared no HVS-I sequences
      in common, although individually they shared such sequences with a variety of
      other Siberian and East Asian populations. In addition, phylogenetic and
      principal component analyses data of mtDNA sequences show that the Tuvinians
      clustered more closely with Turkic-speaking Yakuts, whereas the Mongolic-speaking
      Buryats clustered closer to Korean populations. Furthermore, HVS-I sequences,
      comprising one-fourth of the Buryat lineages and characterized by the only C-to-T
      transition at nucleotide position 16223, were identified as different RFLP
      haplotypes (B, C, D, E, M*, and H). This finding appears to indicate the putative
      ancestral state of the 16223T HVS-I sequences to Mongoloid macrohaplogroup M, at
      least. Finally, the results of nucleotide diversity analysis in East Asian and
      Siberian populations suggest that Central and East Asia were the source areas
      from which the genetically heterogeneous Tuvinians and Buryats first emerged.

PMID- 11236867
TI  - Apolipoprotein E polymorphism in the Indian and Mestizo populations of Mexico.
AB  - Apolipoprotein E (APOE) genotypes were determined in 75 Mazatecan Indians and 83
      Mexican mestizos. APOE allele and genotype frequencies in Mazatecans and mestizos
      were similar, with high frequencies of the APOE*3 allele (0.900 and 0.915,
      respectively) and the E3/3 genotype (0.813 and 0.831, respectively) and an
      absence in both samples of the APOE*2 allele. Our data are similar to those
      previously described for Mexican-American and Mayan populations, which show the
      highest frequency worldwide of the APOE*3 allele and the E3/3 genotype.
      Mazatecans and mestizos also show a decreased frequency of the APOE*4 allele when
      compared to other Amerindian groups. The absence of the APOE*2 allele has also
      been reported in other Amerindian groups such as Mayans and Cayapa, whereas in
      Caucasians the average frequency of this allele is about 8%. Our data are in
      agreement with previous reports showing absence of the APOE*2 allele in Native
      American groups. These findings suggest that the APOE*2 allele was absent in
      humans from northern Asia who settled in the Arctic and populated the American
      continent.

PMID- 11236868
TI  - Genetic variation among four Mexican populations (Huichol, Purepecha, Tarahumara,
      and Mestizo) revealed by two VNTRs and four STRs.
AB  - Allele distributions of two polymorphisms with variable number of tandem repeats
      (VNTR), D1S80 and APOB, and four polymorphisms with short tandem repeats (STR),
      VWA, TH01, CSF1PO, and HPRTB, were analyzed in three Mexican ethnic groups:
      Huichol, Purepecha, and Tarahumara. Genotype distribution was in agreement with
      Hardy-Weinberg expectations for each locus and ethnic group. Heterozygosity (H),
      power of discrimination, and probability of exclusion were estimated. The three
      groups presented some distinctive genetic features: (1) a diminished genetic
      diversity (H = 66.8% to 73.4%) and mean number of alleles by locus (5.8 to 6.3)
      in comparison with Mexican mestizos (H = 78.3%, 10.5 alleles/locus), and (2)
      uneven allele distributions as evidenced by "distinctive alleles" with high
      frequencies, especially in the Tarahumara and the Huichol. Genetic relatedness
      analysis included data from a previously typed mestizo population, the largest
      and most widely distributed population in Mexico. Allele distribution
      differentiation was observed among all four groups, except between mestizo and
      Purepecha (p > 0.05), which was interpreted as indicating a larger Spanish
      component in the Purepecha as a result of gene flow effects. Although
      intrapopulation inbreeding (FIS) was not significant, heterozygote deficiency in
      the total population (FIT) and divergence among populations (FST) were
      significant (p < 0.05). Genetic distances displayed a closer relationship among
      mestizos, Purepechas, and Huichols in relation to Tarahumaras. Correlation
      between the observed genetic features and the geographic isolation level points
      to genetic drift as the main cause of differentiation among these Mexican
      populations.

PMID- 11236869
TI  - The population structure of ten Newfoundland outports.
AB  - Island populations are most informative in the study of the genetic structure of
      human aggregates. These populations are often of small size, thus violating the
      Hardy-Weinberg assumption of infinite size. Some geographically isolated island
      populations are further subdivided by religion, ethnicity, and socioeconomic
      factors, reducing their effective sizes and facilitating genetic changes due to
      stochastic processes. Because of extreme geographic and social isolation, fishing
      communities or outports of Newfoundland have been investigated for genetic
      microdifferentiation through the founder effect and genetic drift (Crawford et
      al. 1995). The purpose of this paper is to examine the population structure of 10
      Newfoundland outports using the allelic frequencies derived from 12 red cell
      antigens. To achieve this goal, first we calculated gene frequencies using
      maximum-likelihood estimation procedures. Second, we used R-matrix methods to
      explore population differentiation. Third, we regressed mean per-locus
      heterozygosity on genetic distance from the gene frequency centroid to identify
      the most isolated populations. On the basis of this information, the three
      outports of Seal Cove, Island Harbor, and Tilting were found to be genetically
      differentiated from the other small populations. Moreover, religious and
      geographic subdivisions appear to explain the observed genetic variation.

PMID- 11236871
TI  - A MATLAB package for the EIDORS project to reconstruct two-dimensional EIT
      images.
AB  - The EIDORS (electrical impedance and diffuse optical reconstruction software)
      project aims to produce a software system for reconstructing images from
      electrical or diffuse optical data. MATLAB is a software that is used in the
      EIDORS project for rapid prototyping, graphical user interface construction and
      image display. We have written a MATLAB package (http://venda.uku.fi/ vauhkon/)
      which can be used for two-dimensional mesh generation, solving the forward
      problem and reconstructing and displaying the reconstructed images (resistivity
      or admittivity). In this paper we briefly describe the mathematical theory on
      which the codes are based on and also give some examples of the capabilities of
      the package.

PMID- 11236870
TI  - The T-SCAN technology: electrical impedance as a diagnostic tool for breast
      cancer detection.
AB  - In this paper we present the T-SCAN technology and its use as a diagnostic tool
      for breast cancer detection. We show, using theoretical models with simplified
      geometries, that displaying planar two-dimensional maps of the currents detected
      at the breast's surface relate to the electric field distribution within the
      breast. This distribution is a manifestation of the bulk spatial inhomogeneities
      in the complex dielectric constant that represent the various tissue types. These
      differences may be used to discriminate between various pathological states. We
      furthermore illustrate a useful classifier, based on admittance data measured up
      to 2 kHz, and we argue that low frequency impedance measurements can be used
      successfully in breast cancer diagnosis.

PMID- 11236872
TI  - A numerical model for magnetic induction tomographic measurements in biological
      tissues.
AB  - A finite-difference model has been developed for simulating measurements in
      magnetic induction tomography (MIT) for biological tissues. The model has three
      stages: (1) computation of the distribution of current induced in a volume of
      dielectric due to the magnetic field from an excitation coil; both the electrical
      conductivity and permittivity of the dielectric are taken into account: (2)
      computation of the e.m.f. induced in the sensing coil directly from the
      excitation coil; (3) computation of the e.m.f. induced in a sensing coil due to
      the current distribution in the dielectric. From the results of stages (2) and
      (3), the change in signal in the sensing coil due to the dielectric can be
      obtained, in magnitude and phase, as a fraction of the signal received in the
      absence of the dielectric. The peak values in the modelled curves agreed to
      within 14% of practical measurements at 10 MHz on volumes of saline solution with
      conductivities in the range 0.7 to 6 S m(-1).

PMID- 11236873
TI  - Sensitivity maps and system requirements for magnetic induction tomography using
      a planar gradiometer.
AB  - We evaluated analytically and experimentally the performance of a planar
      gradiometer as a sensing element in a system for magnetic induction tomography. A
      system using an excitation coil and a planar gradiometer was compared against a
      system with two coils. We constructed one excitation coil, two different sensing
      elements and a high-resolution phase detector. The first sensor was a PCB square
      spiral coil with seven turns. The second sensor was a PCB planar gradiometer with
      two opposite square spirals of seven turns, with a distance between centres of 8
      cm. Theoretical sensitivity maps were derived from basic equations and compared
      with experimental data obtained at 150 kHz. The experimental sensitivity maps
      were obtained measuring the perturbation produced by a brass sphere of 12 mm in
      empty space. The advantage of using a gradiometer is that it can be adjusted to
      give a minimum signal for homogeneous objects, while increasing the sensitivity
      to local perturbations of the conductivity. Results show that a system using a
      planar gradiometer as detector has less demanding requirements for the electronic
      system than a system using simple coils.

PMID- 11236874
TI  - Magnetic induction tomography: hardware for multi-frequency measurements in
      biological tissues.
AB  - Magnetic induction tomography (MIT) is a contactless method for mapping the
      electrical conductivity of tissue. MIT is based on the perturbation of an
      alternating magnetic field by a conducting object. The perturbation is detected
      by a voltage change in a receivercoil. At physiologically interesting frequencies
      (10 kHz-10 MHz) and conductivities (< 2 S m(-1)) the lower limit for the relative
      voltage change (signal/carrier ratio = SCR) to be resolved is 10(-7)-10(-10). A
      new MIT hardware has been developed consisting of a coil system with planar
      gradiometers and a high-resolution phase detector (PD). The gradiometer together
      with the PD resolves an SCR of 2.5 x 10(-5) (SNR = 20 dB at 150 kHz, acquisition
      speed: 100 ms). The system operates between 20 and 370 kHz with the possibility
      of extending the range up to 1 MHz. The feasibility of measuring conductivity
      spectra in the beta-dispersion range of biological tissues is experimentally
      demonstrated. An improvement of the resolution towards SCR = 10(-7) with an SNR
      of > or = 20 dB at frequencies > 100 kHz is possible. On-line spectroscopy of
      tissue conductivity with low spatial resolution appears feasible, thus enabling
      applications such as non-invasive monitoring of brain oedema.

PMID- 11236875
TI  - Time series of EIT chest images using singular value decomposition and Fourier
      transform.
AB  - The aim of this study is to propose a useful method for exploring regional
      ventilation and perfusion in the chest. The paper describes two methods based on
      singular value decomposition (SVD) and Fourier transform (FT) respectively. This
      work shows that power spectral density (PSD) and phase images (derived from the
      Fourier transform) are easier to interpret and more useful tools for exploiting
      in vivo EIT data in healthy volunteers in order to explore the cardiovascular and
      respiratory systems.

PMID- 11236876
TI  - Variability in the cardiac EIT image as a function of electrode position, lung
      volume and body position.
AB  - A study was conducted using the Sheffield electrical impedance tomography (EIT)
      portable system DAS-01 P to determine the change in the cardiac image with
      electrode position, lung volume and body position. Sixteen electrodes were
      positioned in three transverse planes around the thorax at the level of the
      second intercostal space, at the level of the xiphisternal joint, and midway
      between upper and lower locations. Data were collected at each electrode level
      with the breath held at end expiration and after inspiring 0.5, 1 and 1.5 l of
      air with the subject in both the supine and sitting position. These data were
      analysed using a Matlab developed program that calculates the average resistivity
      change in the cardiac region from automatically determined borders. Results show
      significant individual variability with electrode position and air volume. The
      middle electrode most consistently shows an increase in impedance in the region
      of the heart during systole. In some subjects the change in the ventricular
      volume-like curve showed a greater than 50% change as a function of lung volume.
      The pattern of variability with electrode position was not consistent among
      subjects. In one subject MRI images were obtained to compare actual structures
      with those seen in the EIT image. The results suggest that using these electrode
      locations reliable and consistent data, which could be used in clinical
      applications, cannot be obtained.

PMID- 11236877
TI  - Electrical impedance tomography of human brain activity with a two-dimensional
      ring of scalp electrodes.
AB  - Previously, electrical impedance tomography (EIT) has been used to image
      impedance decreases in the exposed cortex of rabbits during brain activity. These
      are due to increased blood volume at the site of the stimulated cortex; as blood
      has a lower impedance than brain, the impedance decreases. During human brain
      activity similar blood flow changes have been detected using positron emission
      tomography (PET) and functional magnetic resonance imaging (fMRI). If blood
      volume also changes then the impedance of human cortex will change during brain
      activity; this could theoretically be imaged with EIT. EIT data were recorded
      from a ring of 16 scalp electrodes in 34 recordings in 19 adult volunteers
      before, during and after stimulation with (1) a visual stimulus produced by an 8
      Hz oscillating checkerboard pattern or (2) sensory stimulation of the median
      nerve at the wrist by a 3 Hz electrical square wave stimulus. Reproducible
      impedance changes, with a similar timecourse to the stimulus, were seen in all
      experiments. Significant impedance changes were seen in 21 +/- 5% (n = 16, mean
      +/- SEM) and 19 +/- 3% (n = 18) of the electrode measurements for visual and
      somatosensory paradigms respectively. The reconstructed 2D EIT images showed
      reproducible impedance changes in the approximate region of the stimulated cortex
      in 7/16 visual and 5/18 somatosensory experiments. This demonstrates that
      reproducible impedance changes can be measured during human brain activity. The
      final images contained spatial noise; the reasons for this and strategies to
      reduce this in future are discussed.

PMID- 11236878
TI  - Validation of a 3D reconstruction algorithm for EIT of human brain function in a
      realistic head-shaped tank.
AB  - Previous work has demonstrated that electrical impedance tomography can be used
      to image human brain activity during evoked responses, but two-thirds of the
      reconstructed images fail to localize an impedance change to the expected
      stimulated cortical area. The localization failure may be caused by modelling the
      head as a homogenous sphere in the reconstruction algorithm. This assumption may
      lead to errors when used to reconstruct data obtained from the human head. In
      this study a 3D reconstruction algorithm, based on a model of the head as a
      homogenous sphere, was characterized by simulating the algorithm model, the head
      shape and the presence of the skull in saline-filled tanks. EIT images of a
      sponge, 14 cm3 volume with a resistivity contrast of 12%, were acquired in three
      different positions in tanks filled with 0.2% saline. In a hemispherical tank, 19
      cm in diameter, the sponge was localized to within 3.4-10.7% of the tank
      diameter. In a head-shaped tank, the errors were between 3.1 and 13.3% without a
      skull and between 10.3 and 18.7% when a real human skull was present. A
      significant increase in localization error therefore occurs if an algorithm based
      on a homogeneous sphere is used on data acquired from a head-shaped tank. The
      increased error is due to the presence of the skull, as no significant increase
      in error occurred if a head-shaped tank was used without the skull present,
      compared to the localization error within the hemispherical tank. The error due
      to the skull significantly shifted the impedance change within the skull towards
      the centre of the image. Although the increased localization error due to the
      skull is not sufficient to explain the localization errors of up to 50% of the
      image diameter present in the images of some human subjects, the future use of a
      realistic head model in the reconstruction algorithm is likely to reduce the
      localization error in the human images due to the presence of the skull.

PMID- 11236879
TI  - Observation of skin thermal inertia distribution during reactive hyperaemia using
      a single-hood measurement system.
AB  - An attempt was made to image the thermal inertia (defined as the square root of
      the product of thermal conductivity, specific heat and density) of the skin to
      observe the distribution of blood in the skin during post-occlusive reactive
      hyperaemia in normal healthy volunteers. The method was based on the ability to
      calculate thermal inertia by successive thermographic measurements of the skin
      after stepwise change in ambient radiation temperature surrounding the skin area.
      The stepwise change was achieved within 0.1 s through a single hood.
      Experimentation on the undisturbed volar forearm of normal subjects at the same
      site showed that the measurements thus achieved were reproducible. The thermal
      inertia values of forearm skin in normal subjects were scattered throughout the
      range 1.1 x 10(3) to 1.7 x 10(3) W s(1/2) m(-2) K(-1). Experiments on forearm
      skin subjected to arterial cuff occlusion indicated that thermal inertia can be
      detected at a low level of blood perfusion. A linear relationship was observed
      between thermal inertia and blood perfusion measured by laser Doppler imager
      before and during blood flow occlusion. During reactive hyperaemia, the thermal
      inertia image exhibited a non-uniform island-shaped pattern of distribution over
      the forearm, suggesting that, after release from occlusion, recovery of blood
      flow is non-uniform.

PMID- 11236880
TI  - Impedance analyser module for EIT and spectroscopy using undersampling.
AB  - In this paper we present the concept, the design and the test procedure for a DSP
      based high-precision and high-performance wide-band (up to 10 MHz) bioimpedance
      analyser module for application in EIT or bioimpedance spectroscopy. The module
      implements a digital concept with appropriate signal conditioning hardware for
      voltage and current measurement, early signal digitization and subsequent digital
      signal processing in order to calculate the components of impedance (or
      admittance). At low frequencies, the module utilizes the conventional direct
      conversion method, whereas at high frequencies the undersampling technique is
      used. The advantages of the described system are the following: (a) the frequency
      range is extended to higher frequencies, (b) the number of data sampled per time
      interval is significantly reduced, and (c) the current consumption and the costs
      of the ADCs can be significantly reduced. The validation procedure is performed
      by comparing the measured and theoretical values of the magnitude and the phase
      of the impedance for a commonly used tissue model. The module offers an accuracy
      of better than 0.012% for the magnitude of impedance and better than 0.02 degrees
      for the phase.

PMID- 11236881
TI  - Influence of overlying tissue and probe geometry on the sensitivity of a near
      infrared tissue oximeter.
AB  - In this paper, the influences of overlying tissue and detecting distance between
      the source and the detector on the measurement of a tissue oximeter were
      discussed. The signal-noise-ratio of the detector was also examined. A semi
      infinite multi-layer Monte Carlo model was induced to simulate the migration of
      the photons in the skin, adipose and muscle. The thickness of the adipose layer
      and the separation between the source and the detector in the muscle were changed
      to simulate the clinical application. Partial pathlength was introduced as a
      characteristic parameter to evaluate the sensitivity of the oximeter. A two
      wavelength (700 and 830 nm) tissue oximeter was developed to verify the results
      of the simulation. The Monte Carlo simulation results showed that the sensitivity
      of the near infrared spectroscopy (NIRS) oximeter declined greatly with
      increasing overlying tissue thickness. Increasing the distance between the light
      source and the detector improved the sensitivity. However, in order to achieve a
      sufficiently high signal-to-noise ratio, it was necessary to limit this distance.
      The results of a bicycle ergometer exercise verified the above results and showed
      that, for a special adipose thickness (AT), there may be a reasonable range of
      the emitter-detector separation.

PMID- 11236882
TI  - Analysis by mathematical model of haemodynamic data in the failing Fontan
      circulation.
AB  - Several late complications jeopardize the clinical performance of recipients of
      the Fontan operation. The underlying causes have been referred to disturbed flow
      dynamics in the cavopulmonary connections. Presumably, the large pressure drops
      occurring in the inferior and superior connections play a pivotal role in the
      pressure level of the entire circulation, especially in the venous. To address
      this issue, we retrospectively reviewed catheterization data of six patients with
      failing Fontan circulation and compared them with those of six patients with
      functioning Fontan circulation. The impact on the systemic and pulmonary pressure
      of the increase in the cavopulmonary connection resistances was studied through a
      steady-state mathematical model of the univentricular closed-loop circulation. In
      the patients with failing Fontan, pressure in the venae cavae was found to be
      significantly higher, especially at the inferior cava (19.3 +/- 2.2 versus 12.5
      +/- 2.3 mmHg) with the pressure drop at the inferior cavopulmonary connection
      significantly increased (4.7 +/- 3.1 versus 0.33 +/- 0.82 mmHg). The proposed
      mathematical model permits us to clearly relate the pressure increase in the
      venae cavae to an increased resistance in the cavopulmonary connections.
      Therefore, the present analysis confirms that, to avoid possible congestion of
      venous circulation, the definitive palliation of univentricular heart should not
      cause pressure drops at the cavopulmonary connections.

PMID- 11236883
TI  - Investigation of the human oesophagus as a new monitoring site for blood oxygen
      saturation.
AB  - Pulse oximeter probes placed peripherally may fail to give accurate values of
      arterial blood oxygen saturation (SpO2) when peripheral perfusion is poor. Since
      central blood flow may be preferentially preserved, the oesophagus was suggested
      as an alternative monitoring site. A reflectance oesophageal
      photoplethysmographic (PPG) probe and a multiplexed data acquisition system,
      operating simultaneously at two wavelengths and incorporating an external three
      lead electrocardiogram (ECG) reference channel, has been developed. It has been
      used to investigate the suitability of the oesophagus as a possible monitoring
      site for SpO2 in cases of compromised peripheral perfusion. Oesophageal PPG
      signals and standard ECG traces were obtained from 16 anaesthetized patients and
      displayed on a laptop computer. Measurable PPG signals with high signal-to-noise
      ratios at both infrared and red wavelengths were obtained from all five
      oesophageal depths investigated. The maximum PPG amplitude occurred at 25 cm from
      the upper incisors in the mid-oesophagus. The measured pulse transit times (PTTs)
      to the oesophagus were consistent with previous measurements at peripheral sites
      and had a minimum value of 67 +/- 30 ms at a depth of 30 cm. There was broad
      agreement between the calculated values of oesophageal SpO2 and those from a
      commercial finger pulse oximeter.

PMID- 11236884
TI  - Effect of changes in lung volume on acoustic transmission through the human
      respiratory system.
AB  - The variation of acoustic attenuation with lung density was determined in
      experimental studies on seven healthy human volunteers, using a change of lung
      volume as a means of varying lung density. White noise between 50 and 680 Hz was
      introduced into the mouth and the transmitted signals were recorded with four
      microphones on the posterior chest wall (left/right, top/base) at 24, 40, 60 and
      80% of total lung capacity. The change in lung volume had a frequency-dependent
      effect on acoustic attenuation in all subjects. A frequency between 177 and 243
      Hz was identified, where altering the lung volume between 24 and 80% of total
      lung capacity induced a change in attenuation of only 1.0 (+/-0.5) to 2.7 (+/
      1.8) dB, while at a frequency of 364-436 Hz marked variations in attenuation 8.9
      (+/-2.0) to 21.5 (+/-4.8) dB occurred with similar lung volume changes.

PMID- 11236885
TI  - Progress in non-invasive respiratory monitoring using uncalibrated breathing
      movement components.
AB  - The theory for optimal linear combination of uncalibrated breathing movements was
      developed and applied in non-invasive respiratory monitoring situations for
      assessment. 16 patients were monitored overnight for respiratory depression
      during postoperative pain treatment. Intranasal/extra-oral airway pressure
      monitoring and pulse oximetry signals were recorded at 50 Hz. Respiratory
      inductive plethysmography (RIP) provided guidance to nurses regarding sensitivity
      settings of the pressure device during slow, shallow breathing, and vital
      information about breathing movements to help distinguish central from
      obstructive apnoeas. Subsequent analysis showed that the principal components of
      the standardized RIP signals would be helpful in any automated identification of
      pressure indicator false alarms and could provide a simple means for
      supplementary breath classification. The sum and difference of the scaled RIP
      values tracked changes in tidal volume and indicated any breathing movement
      asynchrony or paradox associated with obstructions. A construction was developed
      for emulating RIP calibration predictions of relative changes in tidal volume to
      within about 1%, so that invasive or demanding monitoring preparations could be
      by-passed altogether. The necessary signal combination and linearcalibration
      model background is reviewed for this simple formulation, which arises from
      component analysis and least squares regression. The methods are illustrated for
      definitive non-invasive postoperative monitoring and calibration situations.
      Theoretical and physiological reasons for preferring the use of balanced ribcage
      and abdomen contributions to overall tidal volume are presented that also help
      clarify the greater limitations of traditional RIP monitoring practices.

PMID- 11236887
TI  - An improved data acquisition method for electrical impedance tomography.
AB  - Isaacson, Cheney and Seager have demonstrated that simultaneously applying
      trigonometric patterns of current to a circular electrode array optimizes the
      sensitivity of EIT to inner structure. We have found that it is less desirable to
      measure voltage at an electrode that also applies a current due to variable
      contact impedance. In order to preserve the optimum sensitivity while minimizing
      the effect of electrode artefacts, we have devised an approach where we
      sequentially apply a current between each individual electrode and a separate,
      fixed ground while measuring voltages at all other electrodes for each
      consecutive current impulse. By adding weighted sums of both the applied currents
      and corresponding measured voltages from individual passes, we can synthesize
      trigonometric patterns of any spatial frequency. Since only one of the electrodes
      in any given acquired data set is used as a source, this approach significantly
      dilutes the effect of contact impedance on the resulting voltage measurements. We
      present simulated data showing the equivalency between the synthesized and actual
      trigonometric excitation patterns. In addition, we report experimental data, both
      in vitro and in vivo, that show improved results using this data acquisition
      technique.

PMID- 11236886
TI  - Dartmouth's next generation EIS system: preliminary hardware considerations.
AB  - Our previous system covered the frequency range of 0 to 1 MHz. In this new design
      we propose to cover the range from 0 to 10 MHz. The higher frequencies have
      forced us to reconsider several design decisions in view of both the physics of
      the problem and the performance of available electronic components. In this
      presentation we examine in detail the constraints faced by the designer, starting
      from wiring consideration to measurement techniques. We will also present the
      solutions we selected to overcome the limitations we discovered. The problems
      include phase detection, amplitude measurements, system organization and layout
      and finally system calibration.

PMID- 11236888
TI  - Preliminary results from an EIT breast imaging simulation system.
AB  - An electrical impedance tomography (EIT) simulation system for breast imaging has
      been developed using impedance data from a previous study and a finite-element
      model (FEM). This system has the functionality to construct various models of the
      breast, image the boundary voltages developed from any injection schema and
      provide parametric Cole-Cole modelling. Simulations indicate that breast
      carcinoma can be imaged and multi-frequency Cole-Cole dispersion data can be
      extracted. This is intended as the first stage towards providing an artificial
      intelligence based system capable of producing clinically relevant analytical
      data.

PMID- 11236889
TI  - Mk3.5: a modular, multi-frequency successor to the Mk3a EIS/EIT system.
AB  - This paper describes the Sheffield Mk3.5 EIT/EIS system which measures both the
      real and imaginary part of impedance at 30 frequencies between 2 kHz and 1.6 MHz.
      The system uses eight electrodes with an adjacent drive/receive electrode data
      acquisition protocol. The system is modular, containing eight identical data
      acquisition boards, which contain DSPs to generate the drive frequencies and to
      perform the FFT used for demodulation. The current drive is in three sequentially
      applied packets, where each packet contains ten summed sine waves. The data
      acquisition system is interfaced to a host PC through an optically isolated high
      speed serial link (RS485) running at 2 Mbaud (2 Mbits s(-1)). Measurements on a
      saline filled tank show that the average signal to noise performance of the
      system is 40 dB measured across all frequencies and that this figure is
      independent of frequency of measurement. These results suggest that the current
      system is 10 dB better in absolute terms than the previous Sheffield (Mk3a)
      system.

PMID- 11236890
TI  - Solving the forward problem in electrical impedance tomography for the human head
      using IDEAS (integrated design engineering analysis software), a finite element
      modelling tool.
AB  - If electrical impedance tomography is to be used as a clinical tool, the image
      reconstruction algorithms must yield accurate images of impedance changes. One of
      the keys to producing an accurate reconstructed image is the inclusion of prior
      information regarding the physical geometry of the object. To achieve this, many
      researchers have created tools for solving the forward problem by means of finite
      element methods (FEMs). These tools are limited, allowing only a set number of
      meshes to be produced from the geometric information of the object. There is a
      clear need for geometrical accurate FEM models to improve the quality of the
      reconstructed images. We present a commercial tool called IDEAS, which can be
      used to create FEM meshes for these models. The application of this tool is
      demonstrated by using segmented data from the human head to model impedance
      changes inside the head.

PMID- 11236891
TI  - A realistic three dimensional FEM of the human head.
AB  - A realistic three-dimensional finite element model (FEM) of the human head has
      been developed. Separate layers for the scalp, skull, cerebrospinal fluid (CSF)
      and brain were modelled. Hexahedral elements, a special master matrix assembly
      technique and an iterative successive over-relaxation (SOR) solution scheme were
      employed. This approach enabled rapid modelling with minimal memory requirements,
      which makes this method practical if used for electrical impedance tomography
      (EIT) or source localization inverse problems. Compared to scalp electrodes,
      subdural voltage sensing electrodes were three to four times more sensitive close
      to an oedema or source region, if it was peripheral, but this decreased to 30%
      40% for central oedema or source regions. Scalp current injecting electrodes are
      preferable, since the maximum allowable current is 10 times larger than that of
      the subdural ones. The distance of voltage sensing electrodes from a region to be
      imaged highly affects sensitivity, so depth electrodes will be more sensitive,
      provided that they are close to the region of interest. Finally, the electrode
      size has significant effects on the input or transfer impedance.

PMID- 11236892
TI  - Realistic 2D human thorax modelling for EIT.
AB  - Electrical impedance tomography is a technique that permits estimation of
      resistivity within a subject by reconstructing from boundary measurements. Due to
      the ill conditioning of the problem, images are greatly affected by boundary
      errors. Reconstruction algorithms account for boundary shape and electrode
      position by using a forward solver. In this paper is presented the realization of
      a 2D realistic thoracic model as a better approach compared to circular meshing.
      Several meshes with different discretizations are compared in terms of accuracy
      with a complete electrode model forward solver. By comparing the different
      discretizations it is possible to choose an appropriate mesh density for the 2D
      EIT problem.

PMID- 11236893
TI  - Generalized optimal current patterns and electrical safety in EIT.
AB  - There are a number of constraints which limit the current and voltages which can
      be applied on a multiple drive electrical imaging system. One obvious constraint
      is to limit the maximum ohmic power dissipated in the body. Current patterns
      optimizing distinguishability with respect to this constraint are singular
      functions of the difference of transconductance matrices with respect to the
      power norm (the optimal currents of Isaacson). If one constrains the total
      current (L1 norm) the optimal patterns are pair drives. On the other hand if one
      constrains the maximum current on each drive electrode (an L(infinity) norm), the
      optimal patterns have each drive channel set to the maximum source or sink
      current value. In this paper we consider appropriate safety constraints and
      discuss how to find the optimal current patterns with those constraints.

PMID- 11236894
TI  - A 3D electrical impedance tomography (EIT) system for breast cancer detection.
AB  - A medical device which allows imaging of the distribution of conductivity in 3D
      in regions below the skin surface has been developed and tested. Its purpose is
      to enable early detection and preliminary diagnosis of breast tumours. Design of
      the measuring system and software are described. Results of clinical evaluation
      of the system are presented. EIT images of healthy and cancerous breasts are
      presented and discussed. The system is able to visualize various states of the
      breast and it may be possible to apply it to breast cancer detection.

PMID- 11236895
TI  - Adaptive mesh refinement techniques for electrical impedance tomography.
AB  - Adaptive mesh refinement techniques can be applied to increase the efficiency of
      electrical impedance tomography reconstruction algorithms by reducing
      computational and storage cost as well as providing problem-dependent solution
      structures. A self-adaptive refinement algorithm based on an a posteriori error
      estimate has been developed and its results are shown in comparison with uniform
      mesh refinement for a simple head model.

PMID- 11236896
TI  - Reconstruction of conductivity changes due to ventilation and perfusion from EIT
      data collected on a rectangular electrode array.
AB  - In this paper we demonstrate that conductivity changes caused by ventilation and
      perfusion in a human subject can be reconstructed from electrical impedance
      tomography data collected on a rectangular array of electrodes placed on a
      subject's chest. Currents are applied on the electrodes and the resulting
      voltages on the electrodes are measured. A 3D reconstruction algorithm is used to
      reconstruct the conductivity distribution in the region beneath the array. Time
      traces of the reconstructed conductivity distribution demonstrate the detected
      changes in conductivity due to ventilation and perfusion.

PMID- 11236897
TI  - Injury in the era of genomics.
AB  - The traditional approach to the study of biology employs small-scale
      experimentation that results in the description of a molecular sequence of known
      function or relevance. In the era of the genome the reverse is true, as large
      scale cloning and gene sequencing come first, followed by the use of
      computational methods to systematically determine gene function and regulation.
      The overarching goal of this new approach is to translate the knowledge learned
      from a systematic, global analysis of genomic data into a complete understanding
      of biology. For investigators who study shock, the specific goal is to increase
      understanding of the adaptive response to injury at the level of the entire
      genome. This review describes our initial experience using DNA microarrays to
      profile stress-induced changes in gene expression. We conclude that efforts to
      apply genomics to the study of injury are best coordinated by multi-disciplinary
      groups, because of the extensive expertise required.

PMID- 11236898
TI  - Plasma concentrations and clearance of procalcitonin during continuous veno
      venous hemofiltration in septic patients.
AB  - We determined the elimination characteristics of procalcitonin (PCT) during
      continuous veno-venous hemofiltration (CVVHF) and the resulting effect on PCT
      plasma levels. A prospective study was conducted in patients with sepsis and
      acute oliguric renal failure, treated with CVVHF using a polysulfone membrane
      (Baxter Renaflo II PSHF 1200). Patients had sepsis and PCT plasma levels > 4 ng
      ml(-1) (n = 26). PCT was measured in the pre- and post-filter plasma and the
      ultrafiltrate at 0, 5, 10, and 15 min and 1, 2, 4, 6, 12, and 24 h after setup of
      CVVHF. PCT sieving coefficient was 0.24. Elimination of PCT, however, depended on
      the duration of filtration, because filter adsorption was the main mechanism of
      PCT clearance during the first hour of hemofiltration, finally increasing to a
      clearance of PCT into the ultrafiltrate of 2.8-5.5 mL/min after 2 h. PCT plasma
      levels were not significantly altered during CVVHF (96% of the initial
      concentration after 24 h, P = 0.72). Similar to what has been observed with
      cytokines and other proteins of a comparable molecular weight, PCT is removed
      from the plasma during CVVHF, but plasma PCT levels are unchanged. Thus, PCT can
      be used as a diagnostic parameter even in patients with acute renal failure
      undergoing CVVHF.

PMID- 11236899
TI  - Chemokines and interleukin-18 are up-regulated in bronchoalveolar lavage fluid
      but not in serum of septic surgical ICU patients.
AB  - Our objective was to investigate the levels of chemokines (MIP1-alpha, MCP-1, and
      Gro-alpha), Interleukin-18 (IL-18), and Interleukin (IL-6) in bronchoalveolar
      lavage (BAL) fluid and serum at the onset and ongoing states of sepsis as defined
      by the American College of Chest Physicians/Society of Critical Care Medicine in
      septic surgical ICU patients. Our summary background data was to understand the
      significance of compartmentalized inflammatory mediator production in an
      immunologically active organ (lung) in comparison with levels in the systemic
      circulation. The study group consisted of 20 septic patients and 10 non-septic
      patients on surgical ICU. At the onset of sepsis, both BAL fluid and serum
      samples were taken and levels of MIP-1alpha, MCP-1, GRO-alpha, IL-18, and IL-6
      were measured by ELISA. Furthermore, over a subsequent 8-day period, levels of
      these mediators were determined in serum. In some experiments, IL-18 mRNA levels
      were determined in peripheral blood lymphocytes (PBL) of septic and non-septic
      patients. At the onset of sepsis, MIP-1alpha, MCP-1, GRO-alpha, IL-18, and IL-6
      levels were significantly up-regulated in BAL fluid as compared with non-septic
      controls. In marked contrast, with the exception of IL-18 mRNA and IL-6 peptide,
      there was no increase in serum levels of inflammatory mediators determined both
      at the onset and during the ongoing states of sepsis. Based on the present data,
      monitoring levels of serum chemokines and IL-18 protein as markers of sepsis
      might be misleading since despite their non-detection in serum, they were highly
      up-regulated in the lung tissue compartment. These data might underscore the role
      of MIP-1alpha, MCP-1, GRO-alpha, and IL-18 in the mediation of local tissue
      damage. Furthermore, these findings raise the notion that mediator measurement in
      immunologically active organs might serve as pivotal indicators of sepsis prior
      to the actual fulfillment of specific clinical criteria that defines the patient
      as being septic.

PMID- 11236900
TI  - Fetuin, a negative acute phase protein, attenuates TNF synthesis and the innate
      inflammatory response to carrageenan.
AB  - Activation of the innate immune system, even by relatively innocuous stimuli,
      stimulates the release of cytokines (e.g. TNF) that can injure or kill the host.
      To maintain homeostasis, mammals have evolved a counter-regulatory response that
      suppresses the development of excessively robust inflammation. Fetuin, a 66-kD
      negative acute phase glycoprotein, was first identified in 1944. We recently
      discovered an anti-inflammatory role for fetuin, because it suppressed the
      release of TNF from lipopolysaccharide- (LPS) stimulated macrophages. Here the
      anti-inflammatory effects of fetuin were studied in vivo in an LPS-independent
      model of acute inflammation caused by administration of carrageenan.
      Administration of fetuin (5-500 mg/kg intraperitoneally) dose-dependently
      attenuated the development of paw edema as compared to either asialofetuin (500
      mg/kg) or bovine albumin (500 mg/kg). TNF production in the carrageenan-injected
      paws was significantly inhibited by administration of fetuin (586+/-98 pg
      TNF/paw) as compared to either asialofetuin (1018+/-186 pg TNF/paw) or saline
      (1,005+/-172 pg TNF/paw). When specific anti-fetuin IgG was administered into the
      paw prior to the application of carrageenan, the development of edema formation
      was significantly increased as compared to irrelevant IgG, indicating that
      endogenous fetuin normally attenuates the inflammatory response. These results
      now reveal a previously unrecognized anti-inflammatory role of fetuin in counter
      regulating the innate immune response, and suggest that it may be possible to use
      fetuin as an experimental anti-inflammatory agent.

PMID- 11236901
TI  - In vivo assessment of endothelin-induced heterogeneity of hepatic tissue
      perfusion.
AB  - Specific vasoactive substances such as endothelin (ET) have been proposed to
      induce heterogeneity of tissue perfusion and thus the oxygen delivery at the
      sinusoidal level in the liver, but a direct method for testing this hypothesis
      has not been available. Our objective was to develop a method to test the
      hypothesis that functional heterogeneity of blood flow can be induced at the
      sinusoidal level by mediators such as endothelin-1, which act at the sinusoidal
      level. We constructed oxygen-sensitive membranes using tris (1,10-phenanthroline)
      ruthenium (II) chloral hydrate, a dye whose fluorescence is quenched by oxygen
      incorporated into a silicon rubber membrane. The membrane (less than 40 microm
      thick) was formed on a glass coverslip that served as the viewing window of the
      system for in vivo fluorescence microscopy and allowed determination of the PO2
      distribution in rat liver acini during intraportal infusion of ET or
      phenylephrine (PE) in vivo. Heterogeneity was quantified by comparing the
      coefficient of variation (CV) of the fluorescence intensity within the zone 1
      before, during, and after drug infusion. PE and ET doses were matched to produce
      a similar increase in portal pressure. PE caused a gradient of PO2 across zones,
      but within zone 1 no significant increase in CV was observed. In contrast, ET
      produced a patchy pattern of both an increase and decrease in PO2 resulting in
      doubling (P < 0.01) in CV of fluorescence intensities within zone 1. These
      results indicate that PE, which acts at presinusoidal sites, results in a
      homogeneous decrease in tissue PO2 within a zone, while ET, which additionally
      acts at sinusoidal sites, induces significant microheterogeneity of tissue PO2.
      The oxygen-sensitive membrane provides a useful tool for oxygen mapping in vivo.

PMID- 11236902
TI  - TGF-beta abrogates TCR-mediated signaling by upregulating tyrosine phosphatases
      in T cells.
AB  - TGF-beta is known to inhibit many of the immune cell functions including T cell
      proliferation and IL-2 production. The mechanism of such TGF-beta-mediated
      inhibition of T cell functions is poorly understood. The present study examined
      the effects of TGF-beta on the activation of protein tyrosine kinases (PTK)
      P56lck, P59fyn, and Zap-70, and protein tyrosine phosphatases (PTP) SHP-1 and SHP
      2. A balance between the actions of PTK and PTP is critical for appropriate T
      cell activation. These studies were carried out using nylon wool-purified splenic
      T cells from healthy Sprague-Dawley rats. Results from these studies showed that
      incubation of T cells with TGF-beta inhibited the activation of P56lck, P59fyn
      and Zap-70. The decrease in these three protein tyrosine kinases was accompanied
      by an increase in the activation of the protein tyrosine phosphatase SHP-1. There
      was no change in the phosphorylation of SHP-2 with and without pretreatment of T
      cells with TGF-beta. The decrease in P56lck, P59fyn kinase activity, and Zap-70
      phosphorylation was prevented when T cells were stimulated with anti-CD3 in the
      presence of pervanadate, an inhibitor of PTP. These results suggested that TGF
      beta-mediated inhibition of P56lck, P59fyn, and Zap-70 is likely due to an up
      regulation of protein tyrosine phosphatases such as SHP-1.

PMID- 11236903
TI  - Dantrolene reduces serum TNFalpha and corticosterone levels and muscle calcium,
      calpain gene expression, and protein breakdown in septic rats.
AB  - The effects of dantrolene on serum TNFalpha and corticosterone levels and on
      muscle calcium, calpain gene expression, and protein breakdown were studied in
      rats with abdominal sepsis induced by cecal ligation and puncture. Treatment of
      rats with 10 mg/kg of dantrolene 2 h before and 8 h after induction of sepsis
      reduced serum TNFalpha and corticosterone, muscle calcium levels, mRNA levels for
      m- and mu-calpain, and the muscle specific calpain p94, as well as total and
      myofibrillar protein breakdown rates, determined as release of tyrosine and 3
      methylhistidine, respectively, from incubated extensor digitorum longus muscles.
      The results support the concept that increased calcium concentrations may be an
      important mechanism of sepsis-induced muscle protein breakdown. The data also
      indicate that other mechanisms, in addition to reduced muscle calcium
      concentrations such as decreased levels of TNFalpha and glucocorticoids, may
      contribute to the anti-catabolic effects of dantrolene during sepsis. The
      observations are important from a clinical standpoint because they suggest that
      the catabolic response in skeletal muscle during sepsis may be prevented by
      treatment with a calcium antagonist.

PMID- 11236904
TI  - Effects of dobutamine on hepato-splanchnic hemodynamics in an experimental model
      of hyperdynamic endotoxic shock.
AB  - Dobutamine infusion has been proposed to increase splanchnic blood flow in septic
      conditions, but its' effects on liver blood flow and metabolism have not been
      well defined. We investigated the effects of dobutamine on liver blood flow,
      metabolism, and pathology in a canine hyperdynamic endotoxic shock model. Twenty
      one dogs were anesthetized and paralyzed. After the administration of 2 mg/kg
      endotoxin, normal saline was infused to restore the pulmonary artery-occluded
      pressure to 10 mmHg. The dogs were then randomized to receive fluids either alone
      (n = 7) or combined with a dobutamine infusion at a rate of 5 (n = 7) or 10
      microg/kg per min (n = 7). After initial fluid resuscitation, cardiac index (CI)
      increased from 152+/-48 to 386+/-97 mL/kg per min (P < 0.01) and then slightly
      decreased with time in the control group, but further increased to 458+/-54 mL/kg
      per min (P< 0.05) and remained elevated in the group treated with 5 microg/kg per
      min of dobutamine. Portal vein and hepatic arterial blood flows followed a
      similar course and increased with fluid resuscitation. Both decreased with time
      in the control group, but further increased in the dobutamine-treated animals.
      Liver oxygen delivery (DO2liv) increased with fluids from 2.2+/-2.4 to 3.8+/-1.9
      mL/kg per min (P < 0.01) and further increased in the dobutamine-treated animals
      to 4.1+/-1.2 mL/kg per min. This was associated with an increase in liver oxygen
      uptake from 1.6+/-1.6 to 2.9+/-1.1 mL/kg per min with fluid resuscitation and a
      further increase to 4.3+/-1.5 mL/kg per min with dobutamine administration.
      Lactate consumption and hepatic vein oxygen saturation increased with initial
      fluid resuscitation and then decreased with time in the control group, but not in
      the dobutamine-treated animals. Increasing the dose of dobutamine to 10 microg/kg
      per min did not alter this response. At the end of the experiment, liver tissue
      samples were obtained for microscopic studies. The histological lesions seen in
      the control group were unaffected by dobutamine. In conclusion, dobutamine
      increases liver blood flow and metabolism, but does not affect microscopic
      findings in this hyperdynamic endotoxic shock model.

PMID- 11236905
TI  - Alterations in arginine metabolic enzymes in trauma.
AB  - Arginine is the sole substrate for nitric oxide (NO) synthesis by NO synthases
      (NOS) and promotes the proliferation and maturation of human T-cells. Arginine is
      also metabolized by the enzyme arginase, producing urea and ornithine, the
      precursor for polyamine production. We sought to determine the molecular
      mechanisms regulating arginase and NOS in splenic immune cells after trauma.
      C3H/HeN mice underwent laparotomy as simulated moderate trauma or anesthesia
      alone (n = 24 per group). Six, 12, 24, or 48 h later, 6 animals from each group
      were sacrificed, and splenectomy was performed and plasma collected. Six separate
      animals had neither surgery nor anesthesia and were sacrificed to provide resting
      values (t = 0 h). Spleen arginase I and II and iNOS mRNA abundance, arginase I
      protein expression, and arginase activity were determined. Plasma NO metabolites
      (nitrite + nitrate) were also measured. Trauma increased spleen arginase I
      protein expression and activity (P = 0.01) within 12 and for at least 48 h after
      injury and coincided with up-regulated arginase I mRNA abundance at 24 h. Neither
      arginase II nor iNOS mRNA abundance in the spleen was significantly increased by
      trauma at 24 h. Plasma nitrite + nitrate was decreased in animals 48 h post
      injury compared to anesthesia controls (P < 0.05). Trauma induces up-regulation
      of arginase I gene expression in splenic immune cells within 24 h of injury.
      Arginase II is not significantly up-regulated at that time point. Arginase I,
      rather than iNOS appears to be the dominant route for arginine metabolism in
      splenic immune cells 24 h after trauma.

PMID- 11236906
TI  - Antithrombin reduces mesenteric venular leukocyte interactions and small
      intestine injury in endotoxemic rats.
AB  - We examined the hypothesis that recombinant human antithrombin would reduce
      mesenteric venule leukocyte adhesion and small intestine injury in endotoxemic
      rats. Endotoxemic (endotoxin 10 mg/kg, intravenously) rats were treated either
      with saline or recombinant human antithrombin (250 and 500 U/kg). In some rats,
      indomethacin (100 mg/kg, intraperitoneally) was injected 60 min prior to
      endotoxin and recominant human antithrombin (500 U/kg) treatment. Compared to
      controls, intravital videomicroscopy of the mesentric venule showed an increase
      of leukocyte rolling (55+/-17 versus 70+/-19 leukocytes/min; P < 0.05) and firm
      adhesion (1.1+/-0.3 versus 5.8+/-0.8 leukocytes/100 microm; P < 0.05) in
      endotoxemic rats. Recombinant human antithrombin attenuated endotoxin-induced
      venular endothelium leukocyte adhesive cascade. The beneficial effects of
      recombinant human antithrombin on leukocyte adhesion were inhibited by
      indomethacin (100 mg/kg, intraperitoneally) in endotoxemic rats. Endotoxin
      treatment increased fluorescein isothiocyanate (FITC)-labeled dextran 4,000 (FD4)
      gut lumen to plasma ratio and wet weight/dry weight ratio. Recombinant human
      antithrombin (500 U/kg) attenuated endotoxin-induced gut injury. These
      observations suggest that recombinant human antithrombin reduces endothelium
      leukocyte interactions in endotoxemic rats by interacting with local prostacyclin
      production.

PMID- 11236907
TI  - Methylene blue abolishes aortal tone impairment induced by liver ischemia
      reperfusion in a dose response manner: an isolated-perfused double-organ rat
      model study.
AB  - Liver ischemia-reperfusion (IR) generates remote organ reperfusion injury
      attributable to oxidative mediators. We tested the protective properties of
      methylene blue (MB) on aortal dysfunction. An ex vivo rat liver-aortal ring model
      was used to study the results of aortal exposure to post-ischemia (IR) hepatic
      effluent and its response to phenylephrine and isosorbide dinitrate in the
      absence or presence of increasing concentrations of MB in the effluent. Aortal
      incubation with IR effluents resulted in abnormal contraction. Ring's response to
      the vasoactive drugs was abnormally weak both during and following this exposure.
      Return to stabilization tone was irregular. MB (1.28 mM) best avoided overall
      dysfunction; 0.86 mM was partially effective, and 0.42 mM was ineffective.
      Nitrite/nitrate levels were similar to controls in the only IR 1.28 mM perfusate.
      Liver IR interferes with aortal tone and its response to vasoactive drugs,
      probably via oxidative interaction with nitric oxide. MB reverses these effects
      in a dose-dependent fashion.

PMID- 11236908
TI  - Role of fatty acids in the recovery of cardiac function during resuscitation from
      hemorrhagic shock.
AB  - This study tested the hypothesis that removal of fatty acids as a fuel source
      would improve cardiac efficiency at the expense of reduced cardiac contractile
      function in the isolated working heart after hemorrhage-retransfusion. Non
      heparinized male Sprague-Dawley rats were anesthetized with ketamine-xylazine and
      were hemorrhaged to a mean arterial blood pressure of 40 mmHg for 1 h. Two-thirds
      volume of shed blood was reinfused together with 0.9% NaCl in a volume equal to
      2.3 times the shed blood volume, followed by continuous infusion of 0.9% NaCl at
      10 mL/kg per h for 3 h. Hearts were removed and perfused in closed, recirculating
      working mode for 60 min to measure hydraulic work and cardiac efficiency. Rates
      of glycolysis and glucose oxidation were assessed with [5-3H/U-14C] glucose (11
      mM) in the absence or presence of 0.4 mM palmitate. Compared to baseline
      measurements, hemorrhage-retransfusion significantly reduced arterial blood
      glucose (228+/-7 versus 118+/-12 mg/dL) and non-esterified fatty acid
      concentrations (0.36+/-0.01 versus 0.30+/-0.02 mM), while elevating blood lactate
      (0.8+/-0.1 versus 2.5+/-0.4 mM). Perfusion of sham hearts with glucose-only did
      not alter cardiac work compared to shams perfused with glucose plus palmitate.
      However, shocked hearts perfused with glucose-only demonstrated a significant
      reduction in cardiac work compared to shocked hearts perfused with glucose plus
      palmitate and compared to sham hearts perfused with glucose only (P < 0.05,
      repeated measures ANOVA). Shocked hearts perfused with glucose plus palmitate
      showed no reduction in cardiac work compared to shams. Shocked hearts perfused
      with glucose-only had increased glucose oxidation rates compared to shams
      perfused with glucose plus palmitate. In sham hearts perfused with glucose-only,
      myocardial glycogen and triacylglycerol contents were significantly reduced
      compared to hearts freeze-clamped in situ. These endogenous fuels were not
      decreased in shocked hearts. These data indicate that hemorrhagic shock renders
      the heart unable to mobilize endogenous fuels, and suggest that withdrawal of
      fatty acid oxidation will impair myocardial energy metabolism during
      resuscitation.

PMID- 11236909
TI  - Quantitative assessment of a circulating depolarizing factor in shock.
AB  - Sustained depolarization of cell membranes and cellular edema are known to
      accompany various forms of circulatory shock and probably contribute to
      hypovolemia and cellular dysfunction. It has been proposed that a circulating
      protein is responsible for these effects. In the present study we have confirmed
      the existence of a circulating depolarizing factor (CDF) in hemorrhagic shock,
      burn shock, sepsis, and cardiopulmonary bypass. Plasma samples from pigs or sheep
      in shock were quantitatively assayed for depolarizing activity using a
      microelectrode method on rat diaphragm in vitro. The depolarizing effect of CDF
      in vitro was similar in magnitude to that of shock in situ. We conclude that CDF
      can entirely account for membrane depolarization during shock. The depolarizing
      effect of CDF was dose-dependent and saturable; it could be reversed by rinsing
      the diaphragm with Ringer's or control plasma. CDF activity was detectable in
      plasma within 5 min after a severe scald and gradually increased over the next 25
      min. Resuscitation of hemorrhaged pigs, but not burned sheep, eliminated plasma
      CDF activity.

PMID- 11236910
TI  - What's in a standard?

PMID- 11236911
TI  - Special needs dentistry.

PMID- 11236912
TI  - Evidence and opinion.

PMID- 11236913
TI  - Openness and change.

PMID- 11236914
TI  - The privatisation of NHS dentistry? A national snapshot of general dental
      practitioners.
AB  - There is a prevalent perception that NHS dental treatment is increasingly
      difficult to access. In order to access the validity of this perception data on
      the percentage of private and NHS patients treated by general dental
      practitioners (GDPs) were analysed. These data were derived from a national
      survey. The findings showed that GDPs can be divided into three broad groups on
      the basis of the proportion of patients treated privately or through the National
      Health Service (NHS). Approximately 50% of GDPs nationally concentrate on NHS
      dentistry (85% or more of their patients are treated under the NHS); 25% treat
      more than 70% of their patients privately; the remaining minority of
      practitioners fall between these two positions treating moderate proportions of
      both private and NHS patients. Regional differences also exist in the payment
      systems chosen by GDPs. The median percentage of private patients per dentist
      varies widely by area being around 50% in the South East and South West, 30% in
      London, 20% in the West Midlands and Eastern counties and less than 10%
      elsewhere. In a multivariate regression GDP characteristics were also significant
      in explaining the median percentage of private patients per GDP The findings add
      to widely held concerns about access to NHS dentistry, though suggest that
      problems may be limited to certain areas of the United Kingdom.

PMID- 11236915
TI  - The impact of oral health on people in the UK in 1998.
AB  - Knowledge of the extent of dental disease gives a clinical indication of the
      experience of dental problems but it does not necessarily reflect the problems
      that people experience as a result of their dentition. It is becoming
      increasingly appreciated that the way a disease affects people's lives is just as
      important as epidemiological measures of its prevalence or incidence. The 1998
      Adult Dental Health survey is the first of the decennial series of UK adult
      dental health surveys to use and report a measure of the self-perceived impact on
      people of the dental and periodontal diseases and other oral conditions. Over
      half (51%) of dentate adults said they had been affected in some way by their
      oral health, and in 8% of cases the impact was sufficient to have reduced their
      quality of life.

PMID- 11236916
TI  - Indirect retention.
AB  - This article explains the mechanism of indirect retention for RPDs and discusses
      the factors which determine its effectiveness. Examples are given of designs
      which incorporate indirect retention.

PMID- 11236917
TI  - The outcome of root canal treatment. A retrospective study within the armed
      forces (Royal Air Force).
AB  - OBJECTIVE: The objective of this study was to investigate the outcome of
      conventional root canal treatment in a general practice setting within the Royal
      Air Force dental service. Design Retrospective review. METHODS: Teeth that had
      been root-filled for 12 months or more by Royal Air Force dental practitioners in
      patients attending a large Royal Air Force dental centre were included in the
      study. Following clinical and radiographic review the root fillings were
      classified as 'definitely successful', 'probably successful' or 'failed' The
      effect on success of several variables on the outcome was investigated. RESULTS:
      Out of a total of 406 teeth, 59% were maxillary teeth and 41% were mandibular
      teeth. Sixty-nine per cent of the total sample had pre-existing periapical
      radiolucencies. Cold lateral condensation of gutta-percha was the most widely
      used filling technique (64% of all cases). Fifty per cent of the teeth had root
      fillings within 2 mm of the radiographic apex, 32% were greater than 2 mm from
      the radiographic apex and 18% were overfilled. Cold lateral condensation was the
      most successful (92% overall) filling technique. Maxillary anterior teeth had a
      better success rate (96%) than other tooth types. Teeth with pre-existing
      periapical radiolucencies had a higher success rate (87%) than those cases where
      there was no pre-existing periapical radiolucency (80%). Root fillings that were
      less than 2 mm from the radiographic apex of the tooth had a higher success rate
      (88% overall) than those that were greater than 2 mm from the radiographic apex
      (77% overall). Of the 406 cases, 57% (n=231) were classified as definitely
      successful, 28% (n=114) were classified as probably successful and 15% (n=62)
      were classified as failures. Thus, the overall success rate combining definitely
      successful and probably successful root fillings was 85% (n=344). CONCLUSIONS:
      Root fillings placed using cold lateral condensation of gutta-percha to within 2
      mm of the radiographic apex of the tooth were associated with the best outcome.

PMID- 11236918
TI  - Dental erosion in a group of British 14-year-old, school children. Part I:
      Prevalence and influence of differing socioeconomic backgrounds.
AB  - OBJECTIVES: To establish the prevalence of erosion in a cluster random sample of
      14- year-olds in Birmingham UK. To determine whether socioeconomic group
      influences the prevalence of erosion. METHODS: The study group consisted of a
      cluster random sample of 14-year-old school children in Birmingham UK: 418
      children were examined from 12 different schools; 209 were male and 209 female.
      The level of tooth wear was recorded using a modification of the (TWI) index of
      Smith and Knight (1984). The ACORN classification was used to assess the
      socioeconomic status of all children. RESULTS: Results showed that 48% of the
      children had low erosion, 51% had moderate erosion and only 1% had severe
      erosion. There were statistically significant differences between males and
      females; more males had buccal/labial and lingual/palatal tooth surface erosion
      than females (Chi-square analysis P < 0.001). There was also significantly more
      erosion observed in teenagers in the lowest socioeconomic categories. CONCLUSION:
      It was concluded that moderate levels of dental erosion are common in 14-year-old
      school children and this may lead to increasing clinical problems. There was
      significantly more erosion in children from low socioeconomic groups. Possible
      aetiological factors need to be investigated further.

PMID- 11236919
TI  - Prevalence, age of onset and demographic relationships of different areca nut
      habits amongst children in Tower Hamlets, London.
AB  - OBJECTIVE: To examine prevalence and demographic relationships of different areca
      nut habits amongst children. DESIGN: Self-administered questionnaire. SUBJECTS:
      Children aged between 11 and 15. Of 800 questionnaires distributed, 704 were
      fully completed (88%). SETTING: Two secondary schools in the London district of
      Tower Hamlets. MEASURES: Demographic, areca nut habits used, age first used,
      still using, frequency of use. RESULTS: Users of any areca nut habit were
      exclusively from the South Asian population. Of this population, 77% had engaged
      in a habit, and dependent upon habit between 54 and 92% of these still remained
      current users. The highest prevalence of current use for boys and girls
      respectively was for areca nut alone (36%, 43%), followed by mistee pan (35%,
      29%), betel-quid (27%, 26%) and pan masala (14%, 16%). Of the current users, 44%
      engaged in one habit only, 24% two, 20% three and 13% all four. The highest
      period of risk for starting to use areca nut alone, betel-quid and mistee pan was
      between ages 5 and 12, whilst for pan masala it was after 10. Boys had a
      significantly higher risk of beginning use before 10 (P < .001) and a higher
      frequency of use for pan masala (P< .01), areca nut alone (P< .05) and betel-quid
      (P = .06) than girls. The frequency of using each habit was between 3 and 5
      episodes per week, however boys use pan masala approximately 10 times per week.
      CONCLUSION: South Asian children may already be experienced users of areca nut.
      Greater attention should be directed towards identifying signs of oral submucous
      fibrosis, oral cancer and other potentially malignant lesions within the South
      Asian population.

PMID- 11236920
TI  - Training, re-training and getting back to practice.
AB  - Career breaks occur for many reasons and may well be the pattern for the future.
      In a recent survey, reasons given for career breaks included personal and family
      sickness, childrearing, travelling and study. Childrearing was the most common
      reason for women to have a break and personal sickness for men. Although these
      breaks may be short, they may be multiple and therefore have enormous
      implications for workforce planning.

PMID- 11236921
TI  - Development of a Monte Carlo track structure code for low-energy protons in
      water.
AB  - PURPOSE: The development of a new generation of Monte Carlo track structure code
      is described, which simulates full slowing down of low-energy proton history
      tracks (lephist) in the range 1 keV-1 MeV in water. MATERIAL AND METHODS: All
      primary protons are followed down to 1 keV and all electrons to 1 eV. All primary
      interactions, including elastic scattering, ionization, excitation and charge
      exchange processes by protons and neutral hydrogen were taken into account. Cross
      sections for proton and hydrogen impact were obtained from experimental data for
      water. Where data were lacking, the existing experimental data were fitted and
      extrapolated. The tracks of secondary electrons were generated using the electron
      track code kurbuc. The cross-sections and the energy transfer data were
      individually evaluated for the principal interactions induced by protons and
      hydrogen atoms in water. The analysis starts with the published cross-section
      data for water using a semi-empirical model including contributions from the
      neutral hydrogen atoms. For excitation cross-sections, the original Miller-Green
      analytical formula was used. For ionization by neutral hydrogen atoms, the same
      energy spectrum was assumed for secondary electrons as for protons. The total
      cross-sections were taken from the experiment of Blorizadeh and Rudd (1986b, c).
      For the stripping of charge by neutral hydrogen the data of Toburen et al. (1968)
      were used. RESULTS: Data are presented on total and differential elastic cross
      sections as a function of energy and scattering angle respectively; single and
      double differential cross-sections for secondary electrons ejected by various
      energy proton impact; total cross-sections due to proton and hydrogen impact on
      water; stopping power cross-sections; and fraction of stopping power for water
      for protons as a functions of proton energy. CONCLUSIONS: Tracks were analysed to
      provide confirmation on the reliability of the code and information on physical
      quantities, such as range, W, restricted stopping power, radial dose profiles and
      some microdosimetric parameters. Model calculations show good agreement with the
      experimental and calculated data.

PMID- 11236922
TI  - DNA strand break yields after post-high LET irradiation incubation with
      endonuclease-III and evidence for hydroxyl radical clustering.
AB  - PURPOSE: To determine the increase in single- (SSB) and double-strand break (DSB)
      yields after post-high LET irradiation incubation of plasmid DNA with the
      endonuclease-III (endo-III) of Escherichia coli. MATERIALS AND METHODS: Plasmid
      DNA in aerobic aqueous solution was irradiated with one of five radiation types:
      137Cs gamma-rays (LET approximately 0.3keV microm(-1)), 244Cm alpha-particles
      (140-190 keV microm(-1)), 4He ions (97 keV microm(-1)), 56Fe ions (143 keV
      microm(-1)) or 197Au ions (1,440 keV microm(-1)). The irradiated samples were
      then incubated with endo-III. SSB and DSB yields were quantified by agarose gel
      electrophoresis. RESULTS: Endo-III incubation produced an increase in the SSB and
      DSB yields. The increases were in general lower after the high LET irradiation
      than after gamma-irradiation. This may reflect inhibition of the activity of endo
      III by the nearby DNA damage expected from high LET radiation. It can be shown
      that even if the activity of endo remains unchanged, significantly lower
      increases in SSB and DSB yields would still be expected. CONCLUSION: The results
      provide evidence for clustered DNA damage after high LET irradiation.

PMID- 11236923
TI  - Dose--response of initial G2-chromatid breaks induced in normal human fibroblasts
      by heavy ions.
AB  - PURPOSE: To investigate initial chromatid breaks in prematurely condensed G2
      chromosomes following exposure to heavy ions of different LET. MATERIAL AND
      METHODS: Exponentially growing human fibroblast cells AG1522 were irradiated with
      gamma-rays, energetic carbon (13 keV/ microm, 80 keV/microm), silicon (55
      keV/microm) and iron (140 keV/microm, 185keV/microm, 440keV/microm) ions.
      Chromosomes were prematurely condensed using calyculin-A. Initial chromatid-type
      and isochromatid breaks in G2 cells were scored. RESULTS: The dose response
      curves for total chromatid breaks were linear regardless of radiation type. The
      relative biological effectiveness (RBE) showed a LET-dependent increase, peaking
      around 2.7 at 55-80keV/microm and decreasing at higher LET. The dose response
      curves for isochromatid-type breaks were linear for high-LET radiations, but
      linear-quadratic for gamma-rays and 13 keV/microm carbon ions. The RBE for the
      induction of isochromatid breaks obtained from linear components increased
      rapidly between 13keV/microm (about 7) and 80keV/microm carbon (about 71), and
      decreased gradually until 440 keV/microm iron ions (about 66). CONCLUSIONS: High
      LET radiations are more effective at inducing isochromatid breaks, while low-LET
      radiations are more effective at inducing chromatid-type breaks. The densely
      ionizing track structures of heavy ions and the proximity of sister chromatids in
      G2 cells result in an increase in isochromatid breaks.

PMID- 11236924
TI  - High- and low-LET induced chromosome damage in human lymphocytes: a time-course
      of aberrations in metaphase and interphase.
AB  - PURPOSE: To investigate how cell-cycle delays in human peripheral lymphocytes
      affect the expression of complex chromosome damage in metaphase following high-
      and low-LET radiation exposure. MATERIALS AND METHODS: Whole blood was irradiated
      in vitro with a low and a high dose of 1 GeV u(-1) iron particles, 400MeV u(-1)
      neon particles or y-rays. Lymphocytes were cultured and metaphase cells were
      collected at different time points after 48-84h in culture. Interphase
      chromosomes were prematurely condensed using calyculin-A, either 48 or 72 h after
      exposure to iron particles or gamma-rays. Cells in first division were analysed
      using a combination of FISH whole-chromosome painting and DAPI/ Hoechst 33258
      harlequin staining. RESULTS: There was a delay in expression of chromosome damage
      in metaphase that was LET- and dose-dependant. This delay was mostly related to
      the late emergence of complex-type damage into metaphase. Yields of damage in PCC
      collected 48 h after irradiation with iron particles were similar to values
      obtained from cells undergoing mitosis after prolonged incubation. CONCLUSION:
      The yield of high-LET radiation-induced complex chromosome damage could be
      underestimated when analysing metaphase cells collected at one time point after
      irradiation. Chemically induced PCC is a more accurate technique since problems
      with complicated cell-cycle delays are avoided.

PMID- 11236925
TI  - Adenovirus-mediated wild-type p53 gene expression radiosensitizes non-small cell
      lung cancer cells but not normal lung fibroblasts.
AB  - PURPOSE: We compared the ability of adenoviral-mediated wild-type p53
      RPR/INGN201(Ad5/CMV/p53) to radiosensitize non-small cell lung carcinoma (NSCLC)
      and normal lung fibroblast cells. MATERIALS AND METHODS: NSCLC cell lines (A549
      and H322) and human lung fibroblast cells (MRC-9 and CCD-16) were used in this
      study. Radiosensitivity was determined by clonogenic assay and tumor growth
      delay. Expression of p53, Bax, and p21WAF1 protein were evaluated by immunoblot.
      A FITC conjugate of annexin V was used for flow cytometric detection of
      apoptosis. RESULTS: Clonogenic and apoptotic assays indicated that Ad5/CMV/p53
      enhanced the radiosensitivity of both NSCLC cell lines. On the other hand, the
      two normal human fibroblast cell lines appeared to be resistant to the cytotoxic
      effects of Ad5/CMV/p53 and were not radiosensitized compared to the NSCLC cells.
      According to immunoblot analysis, Bax expression was increased in the NSCLC cells
      treated with the combination therapy; Bax expression, however, was unchanged in
      normal cells. In in vivo studies, tumor growth suppression was enhanced by this
      combination strategy in xenograft tumors growing in nude mice compared to
      Ad5/CMV/p53 or radiation therapy when used alone. CONCLUSIONS: Our data indicate
      that therapy using Ad5/CMV/p53 and irradiation in combination is more effective
      than either treatment when used alone on NSCLC cells, is not limited to cells
      with defective endogenous p53, and does not enhance the radiosensitivity of
      normal cells.

PMID- 11236926
TI  - Comparative effects of combretastatin A-4 disodium phosphate and 5,6
      dimethylxanthenone-4-acetic acid on blood perfusion in a murine tumour and normal
      tissues.
AB  - PURPOSE: To compare the ability of combretastatin A-4 disodium phosphate (CA4DP)
      and 5,6-dimethylxanthenone-4-acetic acid (DMXAA) to change tissue blood
      perfusion. MATERIALS AND METHODS: The tissues were a C3H mouse mammary carcinoma
      and various murine normal tissues, with perfusion measured using the 86RbCl
      extraction technique. RESULTS: CA4DP (250mg/kg; i.p.) reduced tumour perfusion to
      34% of that seen in controls within 1 h of injection. It was maintained at this
      for at least 6 h, returning to control levels by 24 h. This decrease was dose
      dependent. DMXAA (25mg/kg; i.p.) caused a 79% reduction in tumour perfusion 6h
      after injection; no recovery was observed even after 24 h. DMXAA showed no
      changes at doses below 10 mg/kg. Both CA4DP and DMXAA increased perfusion in the
      gut, kidney, bladder and lung, while decreasing splenic perfusion. CA4DP tended
      to decrease perfusion in muscle, while DMXAA increased liver perfusion. These
      changes in normal tissue perfusion were generally less than those changes seen in
      tumours. No significant changes were seen in skin. CONCLUSIONS: CA4DP and DMXAA
      produced a selective and significant reduction in tumour perfusion, but the
      pattern of change was different. These results suggest how these vascular
      targeting drugs should be combined with more conventional therapies.

PMID- 11236927
TI  - Distribution of the number of clonogens surviving fractionated radiotherapy: a
      long-standing problem revisited.
AB  - PURPOSE: A long-standing problem is addressed: what form of the probability
      distribution for the number of clonogenic tumor cells remaining after
      fractionated radiotherapy should be used in the analysis aimed at evaluating the
      efficacy of cancer treatment? Over a period of years, a lack of theoretical
      results leading to a closed-form analytic expression for this distribution, even
      under very simplistic models of cell kinetics in the course of fractionated
      radiotherapy, was the most critical deterrent to the development of relevant
      methods of data analysis. MATERIALS AND METHODS: Rigorous mathematical results
      associated with a model of fractionated irradiation of tumors based on the
      iterated birth and death stochastic process are discussed. RESULTS: A formula is
      presented for the exact distribution of the number of clonogenic tumor cells at
      the end of treatment. It is shown that, under certain conditions, this
      distribution can be approximated by a Poisson distribution. An explicit formula
      for the parameter of the limiting Poisson distribution is given and sample
      computations aimed at evaluation of the convergence rate are reported. Another
      useful limit that retains a dose-response relationship in the distribution of the
      number of clonogens has been found. Practical implications of the key theoretical
      findings are discussed in the context of survival data analysis. CONCLUSIONS:
      This study answers some challenging theoretical questions that have been under
      discussion over a number of years. The results presented in this work provide
      mechanistic motivation for parametric regression models designed to analyze data
      on the efficacy of radiation therapy.

PMID- 11236928
TI  - Different inducibility of radiation- or heat-induced p53-dependent apoptosis
      after acute or chronic irradiation in human cultured squamous cell carcinoma
      cells.
AB  - PURPOSE: This study was undertaken to clarify the effects of acute or chronic pre
      irradiation on the induction of p53-dependent apoptosis by X-rays or heat shock.
      MATERIALS AND METHODS: Having an identical genotype except for p53-status, the
      human cultured squamous cell carcinoma cells (SAS) were transfected with a mutant
      p53 gene (SAS/mp53) or neo alone (SAS/neo) as a control. After acute X
      irradiation (1 Gy min(-1)), chronic gamma-irradiation (0.001 Gy min(-1)) or heat
      shock (44 degrees C), the cells were for the incidence of apoptotic bodies and
      DNA ladders, cellular levels of p53 and bax, and caspase-3 activity. RESULTS: It
      was found that (1) a challenge treatment with X-rays (5.O Gy) or heat shock (30
      min) immediately after chronic pre-irradiation (1.5 Gy) but not acute pre
      irradiation (1.5 Gy) resulted in lower levels of apoptosis than those observed
      after challenge treatment only in SAS/neo cells; (2) a challenge treatment
      induced apoptosis was observed 48 h after cessation of chronic pre-irradiation in
      SAS/neo cells; (3) apoptosis was barely increased in SAS/mp53 cells; and (4) the
      levels of apoptosis-related proteins after challenge treatments were strongly
      correlated with the above phenomena. CONCLUSIONS: Chronic pre-irradiation at a
      low dose-rate suppressed induction of p53-dependent apoptosis via bax and caspase
      3. These findings suggest that chronic pre-irradiation suppressed p53 function
      through radiation-induced signalling and/or p53 stability.

PMID- 11236929
TI  - Overexpression of heat-shock protein 25 augments radiation-induced cell-cycle
      arrest in murine L929 cells.
AB  - PURPOSE: Protective effect of small heat-shock protein (sHSP) against gamma
      radiation, which associated with HSP25-induced cell-cycle delay and Bcl-2
      induction. We further extended our studies on the possible role of HSP25 on
      ionizing radiation-induced cell-cycle regulation. MATERIALS AND METHODS: Flow
      cytometric analyses were performed for cell-cycle distribution and Western
      blotting. Kinase or immunocomplex kinase assay were performed for detection of
      cell-cycle protein expression or activation. RESULTS: Pronounced arrest of G1, S
      and G2/M phase was observed by 4Gy radiation and these arrests were augmented by
      hsp25 overexpression. Inhibition of cyclin-D1, and cyclin-E and induction of
      p21Waf by radiation, which was more pronounced in hsp25 overexpressed cells than
      control cells, which is associated with increased binding activity of CDK2. S
      phase regulator, cyclin-A and its associated CDK2 and CDC2 kinase activities were
      also increased by irradiation and hsp25 overexpression attenuated these
      phenomena. In addition, cyclin-B1 expression and its associated kinase activity,
      which are responsible for the transition of G2 to M phase, were increased by
      radiation and hsp25 overexpression also decreased these phenomena. CONCLUSION:
      HSP25 augmented radiation-induced cell-cycle arrest (G1, S, and G2/M phase) may
      be caused by the HSP25-mediated cell-growth delay and is associated with
      radioresistance.

PMID- 11236930
TI  - Fullerenes as a new class of radioprotectors.
AB  - PURPOSE: To evaluate the radioprotective activity of C3, a regioisomer of water
      soluble carboxyfullerene and a potent free radical scavenger, on both normal and
      tumour cells. MATERIALS AND METHODS: The murine committed bone-marrow stem cells
      for both granulocytes and monocytes (GM-CFC) were used to represent normal cells.
      For tumour cells, murine Ehrlich ascites tumour cells grown in regular tissue
      culture (EAT-T) and in the peritoneal cavity of CD1 mice (EAT-PC) and human HeLa
      cells were used. Cells were preexposed to varying concentrations (1-100
      microg/ml) of C3 at 37 degrees C for 30 min before they were irradiated.
      Clonogenic assays were used to determine survival. The protection factor (PF),
      defined as the ratio of survival with and without C3, was then determined.
      RESULTS: C3 protected GM-CFC in a concentration-dependent manner up to 50
      microg/ml, and no additional protection was seen at 100 microg/ml. The PF was
      1.77 when bone-marrow cells were pre-exposed to 50 microg/ml of C3 before they
      were irradiated with 2 Gy. The value of PF increased to 2.38 when 4 Gy was used.
      In sharp contrast, C3 exerted less radioprotective effect on tumour cells. The PF
      values were 1.07, 1.43 and 1.07 for EAT-T, EAT-PC, and HeLa cells, respectively,
      when 2 Gy was given in the presence of 50 microg/ml of C3. These values increased
      to 1.40, 1.75 and 1.27, respectively, when 4Gy was given. The dose-modifying
      factors at 10% survival were 1.37 and 1.15 for GM-CFC and EAT-PC, respectively.
      CONCLUSION: C3 exhibits a radioprotective effect on a class of normal
      haemopoietic progenitor cells. It also protects tumour cells, but to a lesser
      degree. It appears that C3 and other water-soluble fullerenes have a potential to
      be a new class of cytoprotectors.

PMID- 11236931
TI  - Calcium spiking activity and baseline calcium levels in ROS 17/2.8 cells exposed
      to extremely low frequency electromagnetic fields (ELF EMF).
AB  - PURPOSE: To determine whether extremely low frequency electromagnetic fields can
      alter average free cytosolic calcium ion concentrations [Ca2+]i and transient
      increases in [Ca2+]i in populations of ROS 17/2.8 cells. MATERIALS AND METHODS:
      Cells loaded with the calcium-selective luminescent photoprotein, aequorin, were
      placed in the bottom of a sample chamber, which was inserted into the gap of a
      previously described air gap reactor system where they were exposed either to
      sinusoidal magnetic fields at a variety of frequencies and flux densities or to
      sham conditions. Real-time recordings of photon counts due to aequorin
      luminescence were obtained and data were analysed with the use of probit plots.
      RESULTS: Probit plots of data obtained from cells exposed to the various magnetic
      fields were virtually superimposable over the data obtained for the same cultures
      during pre- and post-exposure sham or no-field periods. CONCLUSION: These
      experiments provided no evidence for any effects of ELF EMF, either positive or
      negative, on either average [Ca2+]i or on transient increases in [Ca2+]i.

PMID- 11236932
TI  - Comments on 'Underestimation of the small residual damage when measuring DNA
      double-strand breaks (DSB): is the repair of radiation-induced DSB complete?'.

PMID- 11236933
TI  - International cooperation post-Chernobyl. Scientific Project Panel of the
      International Cooperation to Establish Post Chernobyl Thyroid Tissue, Nucleic
      Acid and Databanks.

PMID- 11236934
TI  - Biological features of the clone involved in primary amyloidosis (AL).
AB  - Primary light chain-associated amyloidosis (AL) is a plasma cell dyscrasia that
      causes morbidity via systemic tissue deposition of monoclonal light chains in the
      form of fibrils (amyloid). It is the most common form of systemic amyloidosis in
      Western countries and is rapidly fatal. Knowledge of the pathobiology of the
      underlying B cell clone is of primary importance for the design and optimization
      of therapeutic strategies.

PMID- 11236935
TI  - Clinical efficacy of granulocyte transfusion therapy in patients with neutropenia
      related infections.
AB  - Granulocyte transfusions have been advocated by some for the treatment of severe,
      progressive infections in neutropenic patients who fail to respond to
      antimicrobial agents and recombinant hematopoietic growth factors. We conducted
      the current study to determine an appropriate method of granulocyte mobilization
      in healthy donors, and to evaluate the safety and efficacy of granulocyte
      transfusion therapy in patients with neutropenia-related infections. To mobilize
      granulocytes (n=55), healthy normal donors were stimulated in one of the
      following ways: (1) dexamethasone, 3 mg/m2 intravenously 15 min prior to
      leukapheresis (n = 5); (2) granulocyte colony-stimulating factor (G-CSF), 5
      microg/kg subcutaneously 12 to 14 h prior to collection (n=37); or (3) G-CSF and
      dexamethasone (n= 13). The mean granulocyte yield from stimulation with G-CSF
      plus dexamethasone was significantly higher than from stimulation with
      dexamethasone or G-CSF alone. Twenty-five patients with severe neutropenia
      related infections unresponsive to appropriate antimicrobial agents received a
      total of 55 granulocyte transfusions. The patients from whom fungi or Gram
      negative organisms were isolated showed a more favorable response than those
      infected with Gram-positive organisms. However, the responses to the granulocyte
      transfusion therapy could not be correlated with the transfused dose,
      mobilization agents, or the 1 h or 24 h post-transfusion absolute neutrophil
      counts. We conclude that granulocyte transfusion therapy may be clinically useful
      for neutropenia-related infections by fungi or Gram-negative organisms.

PMID- 11236936
TI  - Comparison of the L10M consolidation regimen to an alternative regimen including
      escalating methotrexate/L-asparaginase for adult acute lymphoblastic leukemia: a
      Southwest Oncology Group Study.
AB  - The effectiveness of intensive post-remission chemotherapy regimens for adult
      patients with acute lymphoblastic leukemia (ALL) is limited by both a high rate
      of disease recurrence and a substantial incidence of treatment toxicity. To
      evaluate a potentially more effective and less toxic approach, we conducted a
      multicenter phase III trial of consolidation therapies comparing the standard
      L10M regimen with one combining the brief, intensive L17M regimen and escalating
      methotrexate (MTX) and L-asparaginase (L-asp). Patients over age 15 with
      previously untreated ALL were eligible. Induction therapy included vincristine,
      prednisone, doxorubicin, cyclophosphamide and intrathecal methotrexate
      administered over 36 days. Patients who achieved complete remission (CR) were
      randomized to receive consolidation with either the L10M regimen or with DAT
      (daunomycin, cytosine arabinoside, 6-thioguanine) and escalating MTX and L-asp.
      The randomization was stratified by age, WBC and Ph chromosome status.
      Maintenance therapy was the same in both arms. Of 353 eligible patients, 218
      (62%) achieved CR and 195 were randomized. The treatment arms did not differ
      significantly with respect to disease-free survival (DFS; P= 0.46) or overall
      survival (P= 0.39). Estimated DFS at 5 years was 32% (95% confidence interval
      (CI) 23-42%) in the L10M arm and 25% (95% CI 16-33%) in the DAT/MTX/L-asp arm. In
      each arm, 4% of patients died of toxicities (infection in all but one case).
      Infections and nausea/vomiting were somewhat more common in the L10M arm
      (occurring in 68% and 53% of patients respectively) than the DAT/MTX/L-asp arm
      (56% and 33%). The DAT/MTX/L-asp consolidation regimen was associated with some
      reduction in nonfatal toxicities, but no significant improvement in DFS, overall
      survival or non-relapse mortality when compared to the standard L10M regimen.

PMID- 11236937
TI  - Cytokine-induced restoration of differentiation and cell cycle arrest in v-Myc
      transformed U-937 monoblasts correlates with reduced Myc activity.
AB  - Deregulated expression of the myc-family of oncogenes in hematopoietic and other
      cell types plays an important role in tumorigenesis, and results in increased
      proliferative potential and block of cellular differentiation. We have previously
      shown that IFN-gamma restores phorbol ester-induced differentiation and cell
      cycle arrest in v-myc transformed human U-937 monoblasts. To investigate whether
      other cytokine signals could also abrogate such a block, IL-1, IL-3, IL-4, IL-6,
      IL-7, IL-10, IL-11, LIF, oncostatin M, M-CSF, G-CSF and GM-CSF, and TGFbeta1, TNF
      alpha, IFN-alpha were examined. We show that GM-CSF and IL-6, in combination with
      the phorbol ester 12-O-tetradecanoyl-phorbol acetate (TPA), restored
      differentiation and cell cycle arrest. In contrast, treatment by TGFbeta1 +/- TPA
      resulted in an efficient G1/G0 arrest, but did not appear to induce terminal
      differentiation. Restoration of differentiation and cell cycle arrest was
      accomplished despite maintained expression of the v-Myc protein. Our results show
      that the cytokine-induced signals reduced Myc-dependent transcription of an
      artificial target promoter/reporter gene construct, correlating in most, but not
      all, cases with decreased association of v- and c-Myc with its essential partner,
      Max. Thus, cytokine-induced signals may counteract the activity of deregulated
      Myc, and contribute to the normalization of differentiation, arrest in the G1/G0
      phase of the cell cycle, or both.

PMID- 11236938
TI  - FGF-2 abnormalities in B cell chronic lymphocytic and chronic myeloid leukemias.
AB  - An elevated level of fibroblast growth factor-2 (FGF-2) in peripheral blood is
      considered to play a role in regulating the growth of leukemia cells. Here, we
      show that the level of plasma FGF-2 is increased in 54% of B cell chronic
      lymphocytic leukemias (B-CLL) and in 44% of chronic myeloid leukemias (CML).
      Notably, white blood cells (WBCs) from B-CLL patients contain 18, 22 and 24 kDa
      isoforms of FGF-2 whereas WBCs from CML patients contain only the 24 kDa isoform.
      Furthermore, as cultured B-CLL WBCs release 18 kDa FGF-2 into the medium, they
      constitute a potential source of FGF-2 in the blood. In a receptor binding assay,
      125I-FGF-2 binds weakly to B-CLL WBCs, whereas the ligand binds more strongly to
      CML WBCs. Correspondingly, FGF-2 is unable to activate mitogen-activated protein
      kinase kinase (MEK) and its substrate, extracellular signal-regulated kinase
      (ERK), in B-CLL cells, whereas phosphorylation of both these cell growth-related
      kinases increases following treatment of CML WBCs. We conclude that B-CLL WBCs
      secrete FGF-2 with no apparent autocrine actions. In contrast, WBCs in CML bind
      FGF-2 provided by other FGF-2-hyperproducing cells and activate the MEK/ERK
      kinase cascade, possibly to modulate cell growth.

PMID- 11236939
TI  - CREB antisense oligonucleotides induce non-apoptotic cell death in proliferating
      leukemia cells, but not normal hematopoietic cells, by a bizarre non-antisense
      mechanism.
AB  - We report that antisense phosphorothioate oligodeoxyribonucleotides (PS-ODNs)
      against cyclic AMP response element-binding protein (CREB) induce the death of
      human leukemia cell lines including HL-60, Kasumi-1 and K562, OCI-AML1a and also
      primary leukemia cells isolated from patients with acute myelocytic leukemia and
      chronic myelocytic leukemia in blastic crisis. In contrast, normal human bone
      marrow CD34+ cells and normal peripheral blood lymphocytes were resistant to the
      antisense-mediated cell death. We found that antisense-treated HL-60 cells had
      prominent nuclear fragmentations but lacked apoptotic features including
      internucleosomal DNA cleavage and TUNEL positivity. Cell cycle analysis
      demonstrated a remarkable reduction in G1 phase population along with a mild
      accumulation of S phase and good preservation of G2/M phase, indicating cells
      died at G2/M without cycling into G1 phase. None of the sense-sequenced PS-ODNs
      induced cell death. Further, neither the expression nor the message of CREB
      protein was reduced by antisense treatment, indicating that cell death was
      mediated by a non-antisense mechanism. On the other hand, no consensus
      oligonucleotide sequence for cell death induction was detected. Rather, we found
      a good correlation between the melting temperatures and the anti-proliferative
      activities of the oligonucleotides. Thus, CREB antisense PS-ODNs selectively
      induce a non-apoptotic cell death in leukemic cells by an unknown hybridization
      dependent mechanism.

PMID- 11236940
TI  - Leukemic dendritic cells generated in the presence of FLT3 ligand have the
      capacity to stimulate an autologous leukemia-specific cytotoxic T cell response
      from patients with acute myeloid leukemia.
AB  - It has been proposed that adoptive immunotherapy, for the treatment of relapsed
      AML, with cytotoxic T lymphocytes which show a relative specificity for the
      leukemic cells may have the advantage of maximizing the beneficial anti-leukemic
      effect whilst minimizing the probability of graft-versus-host disease. In this
      study we differentiated peripheral blood AML cells in vitro into functional
      dendritic cells (DCs), as demonstrated by cell morphology, immunophenotype and
      functional activity, in the presence of GM-CSF, IL-4, TNF-alpha and FLT3 ligand.
      Such DCs could be differentiated from 77% of AML patients, irrespective of their
      FAB classification and clinical status and, in all cases tested, the DCs were
      shown to derive from the leukemic clone by FISH analysis. Importantly, from >60%
      of AML patients, autologous T lymphocytes stimulated with these in vitro
      generated leukemic DCs displayed specific cytotoxic activity against AML blasts
      but low reactivity against autologous non-leukemic targets and HLA-matched normal
      PBMNCs therefore suggesting that the CTLs were AML-specific. The use of FLT3
      ligand in our system resulted in a significantly higher number of leukemic DCs as
      compared to cultures from which FLT3 ligand was omitted which is obviously
      advantageous if large numbers of specific CTLs are to be generated in the
      shortest possible time.

PMID- 11236941
TI  - High-dose mitoxantrone + melphalan (MITO/L-PAM) as conditioning regimen supported
      by peripheral blood progenitor cell (PBPC) autograft in 113 lymphoma patients:
      high tolerability with reversible cardiotoxicity.
AB  - Hematological and extrahematological toxicity of high-dose (hd) mitoxantrone
      (MITO) and melphalan (L-PAM) as conditioning regimen prior to peripheral blood
      progenitor cell (PBPC) autograft was evaluated in 113 lymphoma patients (87 at
      disease onset). Autograft was the final part of a hd-sequential (HDS)
      chemotherapy program, including a debulkying phase (1-2 APO +/- 2 DHAP courses)
      and then sequential administration of hd-cyclophosphamide, methotrexate (or Ara
      C) and etoposide, at 10 to 30 day intervals. Autograft phase included: (1) hd
      MITO, given at 60 mg/m2 on day -5; (2) hd-L-PAM, given at 180 mg/m2 on day -2;
      (3) PBPC autograft, with a median of 11 x 10(6) CD34+/kg, or 70 x 10(4) CFU
      GM/kg, on day 0. A rapid hematological recovery was observed in most patients,
      with ANC >500/microL and Plt >20,000/microl values reached at a median of 11 and
      10 days since autograft, respectively. The good hemopoietic reconstitution
      allowed the delivery of consolidation radiotherapy (RT) to bulky sites in 53 out
      of 57 candidate patients, within 1 to 3 months following autograft; five of these
      patients required back-up PBPC re-infusion due to severe post-RT pancytopenia.
      Few severe infectious complications were recorded. There was one single fatal
      event due to severe pancytopenia following whole abdomen RT. Cardiac toxicity was
      evaluated as left ventricular ejection fraction (LVEF), monitored by cardiac
      radionuclide scan. LVEF prior to and after autograft was significantly reduced
      (median values: 55% vs 46%) in 58 evaluated patients; however, a significant
      increase to a median value of 50% was observed in 45 patients evaluated at 1 to 3
      years since autograft. At a median follow-up of 3.6 years, 92 patients are alive,
      with a 7-year overall survival projection and 6.7-year failure-free survival
      projection of 77% and 69%, respectively. We conclude that a conditioning regimen
      with hd-MITOIL-PAM fits well within the HDS program. It implies good tolerability
      and reversible cardiotoxicity and it may have contributed to the good long-term
      outcome observed in this series of patients.

PMID- 11236942
TI  - The bone marrow stromal microenvironment influences myeloma therapeutic response
      in vitro.
AB  - The bone marrow microenvironment supports growth and differentiation of normal
      hematopoietic cells and can contribute to malignant growth. Since myeloma cells
      localize and accumulate in bone marrow, it is important to understand the
      influence of the bone marrow microenvironment not only on the growth of the
      malignant cells, but also on the therapeutic response of myeloma cells. Growth
      factors such as interleukin-6 (IL-6) produced by bone marrow stromal cells can
      protect myeloma cells from glucocorticoid-induced apoptosis. We examined the
      effect of myeloma cells-bone marrow stromal cells interaction in vitro on several
      therapeutic treatments. An interleukin-6-dependent myeloma cell line ANBL6 was
      used and treated with dexamethasone, doxorubicin, and melphalan in the presence
      of bone marrow stromal cells. Stromal cells were able to protect ANBL6 from
      dexamethasone, but significantly enhanced the effect of doxorubicin and
      melphalan. IL-6-induced bcl-XL and cyclin D2 expression in ANBL6 cells, but
      dexamethasone was able to suppress both bcl-XL and cyclin D2 expression in ANBL6.
      Doxorubicin and melphalan were able to suppress bcl-XL expression only in the
      presence of IL-6. We also looked at the effect of activating mutations of N-ras
      in myeloma cells interacting with stromal cells on therapeutic responses.
      Surprisingly, ANBL6 N-ras shows significant resistance to all drugs used.
      Notably, the presence of stromal cells did not alter ANBL6 Nras cells' drug
      resistance. These results suggest both the bone marrow microenvironment and
      genetic alterations of myeloma cells can independently impact on therapeutic
      responses.

PMID- 11236943
TI  - Workshop on minimal residual disease.

PMID- 11236944
TI  - Unequivocal identification of disseminated tumor cells in the bone marrow by
      combining immunological and genetic approaches--functional and prognostic
      information.

PMID- 11236945
TI  - Detection of minimal residual disease in acute lymphoblastic leukemia: the St
      Jude experience.

PMID- 11236946
TI  - Treatment response and residual-disease monitoring in initial and relapsed TEL
      AML1 positive childhood ALL.

PMID- 11236948
TI  - Rapid isolation of chromosomal breakpoints from patients with t(4;11) acute
      lymphoblastic leukemia: implications for basic and clinical research.

PMID- 11236947
TI  - MRD at the end of induction therapy in childhood acute lymphoblastic leukemia:
      outcome prediction strongly depends on the therapeutic regimen.

PMID- 11236949
TI  - Tumor-related alterations in circulating DNA, potential for diagnosis, prognosis
      and detection of minimal residual disease.

PMID- 11236950
TI  - Sequential monitoring of chimerism and detection of minimal residual disease
      after allogeneic blood stem cell transplantation (BSCT) using multiplex PCR
      amplification of short tandem repeat-markers.
AB  - Sequential analysis of chimerism after allogeneic blood stem cell transplantation
      (BSCT) has been shown to be predictive for graft failure and relapse. We have
      explored the impact of a novel approach for the quantitative determination of
      chimerism using a commercial PCR assay with multiplex amplification of nine STR
      loci and fluorescence detection. The feasibility was studied in 121 patients
      transplanted from related or unrelated donors. Follow-up investigation was
      performed in 88 patients. Twenty-eight of these patients had received a
      transplantation after dose-reduced conditioning therapy. Results were compared to
      data obtained by FISH analysis in a subgroup of patients receiving grafts from
      sex-mismatched donors. The analysis was possible in all patients, the median
      number of informative alleles was 4 (range 1-8) compared to 7 (range 1-9) in the
      related and unrelated situation, respectively. A good correlation was seen in 84
      samples from 14 patients analyzed in parallel with STR-PCR and FISH. Decreasing
      values of donor chimerism were detected prior to or concomitantly with the
      occurrence of graft failure and relapse of disease in all patients investigated
      prospectively. Using FACS-sorted material, eg peripheral blood CD34+ cells, the
      assay permitted the detection of residual recipient cells with high sensitivity
      (down to one CD34+ Kasumi cell in 40,000 normal WBC). Evaluation of the inter
      laboratory reproducibility revealed that in 20 samples analyzed in three
      different centers, the median coefficient of variation was 2.1% (range 0.7-9.6%).
      Taken together, the results support the use of the test as a valuable tool in the
      follow-up of patients undergoing allogeneic BSCT. In cases lacking PCR-detectable
      disease-specific gene products, this assay may represent an alternative to
      recently established real-time PCR methods.

PMID- 11236951
TI  - Analysis of chimerism within specific leukocyte subsets for detection of residual
      or recurrent leukemia in pediatric patients after allogeneic stem cell
      transplantation.

PMID- 11236952
TI  - Autologous peripheral blood stem cell transplantation for adult patients with B
      cell lymphoma-associated hemophagocytic syndrome.

PMID- 11236953
TI  - Pathology and the internet.

PMID- 11236954
TI  - Schneiderian papillomas and carcinomas: a review.
AB  - The ectodermally derived Schneiderian mucosa gives rise to an extremely varied
      collection of benign and malignant neoplasms. Prototypical of these are the
      Schneiderian papillomas (inverted, fungiform, and cylindrical cell) and their
      malignant counterparts. Human papilloma virus (HPV) is currently the leading
      candidate as a cofactor in the pathogenesis of the papillomas. Carcinomas arise
      in association with the papillomas in about a 10% frequency. The carcinomas may
      be synchronous or metachronous. Recurrences of the papillomas are the bane of
      surgeons. The magnitude of the recurrences is directly proportional to the
      completeness of removal with the best results obtained by techniques that afford
      the best operative exposure. A comparison of results by different surgical
      procedures is presented. Histologic features sought to predict recurrences or
      malignant transformation have, by and large, not been helpful. Keratinization and
      hyperkeratosis in papillomas, however, are suggested to be sufficiently ominous
      as to warrant further study.

PMID- 11236955
TI  - Sentinel lymph node biopsy in breast cancer: creating controversy and defining
      new standards.
AB  - Sentinel lymph node (SLN) biopsy is an exciting and promising new addition to
      surgical management and pathologic evaluation of breast cancer. Sentinel nodes
      are more likely to contain metastases than nonsentinel nodes providing an
      opportunity to more accurately stage breast cancer patients. In the future,
      surgical management of the axilla may be approached as a staged procedure,
      perhaps eliminating axillary dissection in SLN-negative patients, should clinical
      trials demonstrate the safety of this approach. The advent of SLN biopsy has
      propelled an old question back to the forefront of clinical investigation: do
      occult metastases in lymph nodes have prognostic, predictive, and clinical
      significance? This article provides one opinion and a review on the pathology and
      future of SLN biopsy in breast cancer. Practicing pathologists will need to stay
      abreast of the issues and facts in order to participate in the debate and shape
      the future of pathologic management of sentinel nodes.

PMID- 11236956
TI  - Epithelioid vascular tumors of bone: a review and proposal of a classification
      scheme.
AB  - Skeletal vascular tumors composed of epithelioid endothelial cells commonly
      result in diagnostic difficulty. Although tumors with this morphology have been
      recognized for many years, there is a considerable degree of confusion regarding
      their nomenclature and classification. In this article what is believed to
      represent the morphologic features of this family of tumors is outlined, the
      historical context of epithelioid endothelial tumors is briefly discussed, and
      pertinent literature and texts pertaining to the subject is reviewed. It is
      proposed that the osseous epithelioid endothelial tumors should be classified in
      a similar manner to their soft tissue counterparts and it is suggested that this
      approach should help to clarify the confusion surrounding this subject of
      surgical pathology.

PMID- 11236957
TI  - Surrogate biomarkers of HPV infection in cervical neoplasia screening and
      diagnosis.
AB  - The current prevention of cervical cancer and elimination of its precursors is
      predicated on the identification of cervical cytologic abnormalities and their
      histologic confirmation. This strategy, although effective, depends on both
      sensitivity and specificity of cytology and precise histologic distinction
      between precursor lesions and their mimics during biopsy interpretation. The
      effective application of diagnostic criteria is operator dependent and varies as
      a function of experience and training. However, because human papilloma viruses
      (HPV) are causative agents and alter the cell cycle in cervical neoplasms, host
      genes interacting directly or indirectly with HPV oncoproteins have been
      identified in vitro. Recent research has centered on identifying the host genes
      upregulated in association with HPV infection, determining their suitability as
      "surrogate markers" for HPV infection, and using these markers to identify HPV
      associated epithelial lesions in tissue or cytologic specimens. This review
      surveys recent advances in this field, summarizing the advantages and limitations
      of several candidate biomarkers, including PCNA, Ki-67, cyclin E, p16ink4, MN
      antigen, carcinoembryonic antigen (CEA), and telomerase in the recognition of
      preinvasive cervical neoplasia, and discusses their future potential in cervical
      cancer screening. Based on current studies, the strongest candidates for
      diagnosis and screening are p16 and cyclin E (squamous) and MN (glandular)
      biomarkers. As new genes are identified and tested, the concept of biomarkers as
      tools in primary screening and lesion recognition will continue to mature.

PMID- 11236958
TI  - Can fine needle aspiration cytology adequately diagnose and predict the behavior
      of gastrointestinal stromal tumors?
AB  - The use of endoscopic ultrasound-guided fine needle aspiration is expanding
      rapidly in many centers. This method can be used to produce aspirate specimens
      from masses in the pancreas, liver, retroperitoneum, adrenals, and mediastinum,
      as well as mural nodules in the upper gastrointestinal tract. As application of
      this method continues to grow, it is reasonable to expect that the demand for
      cytologic diagnosis of gastrointestinal stromal tumors will increase. In this
      commentary, the cytologic presentation of one such case is offered. This is used
      to illustrate the clinical, immunohistochemical, and molecular biologic features
      that are used to suggest the prognosis of a given lesion.

PMID- 11236959
TI  - Clear cell sarcoma of the pediatric kidney: detailed description and analysis of
      variant histologic patterns of a tumor with many faces.
AB  - Clear cell sarcoma of the kidney is the most frequently misdiagnosed renal tumor
      in children. The majority of tumors present the classic histologic pattern, which
      allows a definitive diagnosis. However, there are unusual cases with lack of
      "clear" appearance of tumor cells, predominance or exclusive presence of variant
      histologic patterns, and presence of "neoplastic" appearing entrapped tubules.
      Furthermore, a small biopsy specimen may not show the classic histologic pattern.
      These tumors present a diagnostic challenge for the practicing pathologist who
      should be aware of the deviations from the classic histologic features in order
      to make a correct diagnosis.

PMID- 11236960
TI  - Human genomes, public and private.

PMID- 11236961
TI  - And now for the proteome...

PMID- 11236962
TI  - Publication of human genomes sparks fresh sequence debate.

PMID- 11236964
TI  - Physicists worried by grant reforms.

PMID- 11236963
TI  - Call for tighter controls on transgenic foods.

PMID- 11236965
TI  - Reforms woo scientists from mainland China.

PMID- 11236966
TI  - France and Spain join forces over synchrotron project.

PMID- 11236967
TI  - Indian company offers cheap anti-AIDS drugs.

PMID- 11236969
TI  - Fermilab's Tevatron. Back in business.

PMID- 11236968
TI  - Fears grow over melting permafrost.

PMID- 11236970
TI  - Genome timeline. What a long, strange trip it's been...

PMID- 11236971
TI  - Genomics. Are you ready for the revolution?

PMID- 11236973
TI  - Astronomy network will allow every site to shine.

PMID- 11236972
TI  - Skilled eyes are needed to go on studying the richness of the soil.

PMID- 11236974
TI  - Semmelweis and the battle against infection.

PMID- 11236975
TI  - Patents in a genetic age.

PMID- 11236976
TI  - Talking about the genome.

PMID- 11236977
TI  - The beanbag lives on.

PMID- 11236978
TI  - Polymer science. A material fix.

PMID- 11236979
TI  - Quantum physics. Count them all.

PMID- 11236980
TI  - The rising cost of bushmeat.

PMID- 11236981
TI  - Biochemistry. Single-handed cooperation.

PMID- 11236982
TI  - Growth of domesticated transgenic fish.

PMID- 11236983
TI  - Is there a simple theory of sonoluminescence?

PMID- 11236984
TI  - Urinary odour preferences in mice.

PMID- 11236985
TI  - Nuclear fission modes and fragment mass asymmetries in a five-dimensional
      deformation space.
AB  - Nuclei undergoing fission can be described by a multi-dimensional potential
      energy surface that guides the nuclear shape evolution--from the ground state,
      through intermediate saddle points and finally to the configurations of separated
      fission fragments. Until now, calculations have lacked adequate exploration of
      the shape parameterization of sufficient dimensionality to yield features in the
      potential-energy surface (such as multiple minima, valleys, saddle points and
      ridges) that correspond to characteristic observables of the fission process.
      Here we calculate and analyse five-dimensional potential-energy landscapes based
      on a grid of 2,610,885 deformation points. We find that observed fission features
      -such as the distributions of fission fragment mass and kinetic energy, and the
      different energy thresholds for symmetric and asymmetric fission--are very
      closely related to topological features in the calculated five-dimensional energy
      landscapes.

PMID- 11236986
TI  - Experimental violation of a Bell's inequality with efficient detection.
AB  - Local realism is the idea that objects have definite properties whether or not
      they are measured, and that measurements of these properties are not affected by
      events taking place sufficiently far away. Einstein, Podolsky and Rosen used
      these reasonable assumptions to conclude that quantum mechanics is incomplete.
      Starting in 1965, Bell and others constructed mathematical inequalities whereby
      experimental tests could distinguish between quantum mechanics and local
      realistic theories. Many experiments have since been done that are consistent
      with quantum mechanics and inconsistent with local realism. But these conclusions
      remain the subject of considerable interest and debate, and experiments are still
      being refined to overcome 'loopholes' that might allow a local realistic
      interpretation. Here we have measured correlations in the classical properties of
      massive entangled particles (9Be+ ions): these correlations violate a form of
      Bell's inequality. Our measured value of the appropriate Bell's 'signal' is 2.25
      +/- 0.03, whereas a value of 2 is the maximum allowed by local realistic theories
      of nature. In contrast to previous measurements with massive particles, this
      violation of Bell's inequality was obtained by use of a complete set of
      measurements. Moreover, the high detection efficiency of our apparatus eliminates
      the so-called 'detection' loophole.

PMID- 11236987
TI  - Autonomic healing of polymer composites.
AB  - Structural polymers are susceptible to damage in the form of cracks, which form
      deep within the structure where detection is difficult and repair is almost
      impossible. Cracking leads to mechanical degradation of fibre-reinforced polymer
      composites; in microelectronic polymeric components it can also lead to
      electrical failure. Microcracking induced by thermal and mechanical fatigue is
      also a long-standing problem in polymer adhesives. Regardless of the application,
      once cracks have formed within polymeric materials, the integrity of the
      structure is significantly compromised. Experiments exploring the concept of self
      repair have been previously reported, but the only successful crack-healing
      methods that have been reported so far require some form of manual intervention.
      Here we report a structural polymeric material with the ability to autonomically
      heal cracks. The material incorporates a microencapsulated healing agent that is
      released upon crack intrusion. Polymerization of the healing agent is then
      triggered by contact with an embedded catalyst, bonding the crack faces. Our
      fracture experiments yield as much as 75% recovery in toughness, and we expect
      that our approach will be applicable to other brittle materials systems
      (including ceramics and glasses).

PMID- 11236988
TI  - A chiroselective peptide replicator.
AB  - The origin of homochirality in living systems is often attributed to the
      generation of enantiomeric differences in a pool of chiral prebiotic molecules,
      but none of the possible physiochemical processes considered can produce the
      significant imbalance required if homochiral biopolymers are to result from
      simple coupling of suitable precursor molecules. This implies a central role
      either for additional processes that can selectively amplify an initially minute
      enantiomeric difference in the starting material, or for a nonenzymatic process
      by which biopolymers undergo chiroselective molecular replication. Given that
      molecular self-replication and the capacity for selection are necessary
      conditions for the emergence of life, chiroselective replication of biopolymers
      seems a particularly attractive process for explaining homochirality in nature.
      Here we report that a 32-residue peptide replicator, designed according to our
      earlier principles, is capable of efficiently amplifying homochiral products from
      a racemic mixture of peptide fragments through a chiroselective autocatalytic
      cycle. The chiroselective amplification process discriminates between structures
      possessing even single stereochemical mutations within otherwise homochiral
      sequences. Moreover, the system exhibits a dynamic stereochemical 'editing'
      function; in contrast to the previously observed error correction, it makes use
      of heterochiral sequences that arise through uncatalysed background reactions to
      catalyse the production of the homochiral product. These results support the idea
      that self-replicating polypeptides could have played a key role in the origin of
      homochirality on Earth.

PMID- 11236989
TI  - Evidence for non-selective preservation of organic matter in sinking marine
      particles.
AB  - The sinking of particulate organic matter from ocean surface waters transports
      carbon to the ocean interior, where almost all is then recycled. The unrecycled
      fraction of this organic matter can become buried in ocean sediments, thus
      sequestering carbon and so influencing atmospheric carbon dioxide concentrations.
      The processes controlling the extensive biodegradation of sinking particles
      remain unclear, partly because of the difficulty in resolving the composition of
      the residual organic matter at depth with existing chromatographic techniques.
      Here, using solid-state 13C NMR spectroscopy, we characterize the chemical
      structure of organic carbon in both surface plankton and sinking particulate
      matter from the Pacific Ocean and the Arabian Sea. We found that minimal changes
      occur in bulk organic composition, despite extensive (>98%) biodegradation, and
      that amino-acid-like material predominates throughout the water column in both
      regions. The compositional similarity between phytoplankton biomass and the small
      remnant of organic matter reaching the ocean interior indicates that the
      formation of unusual biochemicals, either by chemical recombination or microbial
      biosynthesis, is not the main process controlling the preservation of particulate
      organic carbon within the water column at these two sites. We suggest instead
      that organic matter might be protected from degradation by the inorganic matrix
      of sinking particles.

PMID- 11236990
TI  - Interhemispheric climate links revealed by late-glacial cooling episode in
      southern Chile.
AB  - Understanding the relative timings of climate events in the Northern and Southern
      hemispheres is a prerequisite for determining the causes of abrupt climate
      changes. But climate records from the Patagonian Andes and New Zealand for the
      period of transition from glacial to interglacial conditions--about 14.6-10 kyr
      before present, as determined by radiocarbon dating--show varying degrees of
      correlation with similar records from the Northern Hemisphere. It is necessary to
      resolve these apparent discrepancies in order to be able to assess the relative
      roles of Northern Hemisphere ice sheets and oceanic, atmospheric and astronomical
      influences in initiating climate change in the late-glacial period. Here we
      report pollen records from three sites in the Lake District of southern Chile (41
      degrees S) from which we infer conditions similar to modern climate between about
      13 and 12.2 14C kyr before present (BP), followed by cooling events at about 12.2
      and 11.4 14C kyr BP, and then by a warming at about 9.8 14C kyr BP. These events
      were nearly synchronous with important palaeoclimate changes recorded in the
      North Atlantic region, supporting the idea that interhemispheric linkage through
      the atmosphere was the primary control on climate during the last deglaciation.
      In other regions of the Southern Hemisphere, where climate events are not in
      phase with those in the Northern Hemisphere, local oceanic influences may have
      counteracted the effects that propagated through the atmosphere.

PMID- 11236991
TI  - Evidence of recent volcanic activity on the ultraslow-spreading Gakkel ridge.
AB  - Seafloor spreading is accommodated by volcanic and tectonic processes along the
      global mid-ocean ridge system. As spreading rate decreases the influence of
      volcanism also decreases, and it is unknown whether significant volcanism occurs
      at all at ultraslow spreading rates (<1.5 cm yr(-1)). Here we present three
      dimensional sonar maps of the Gakkel ridge, Earth's slowest-spreading mid-ocean
      ridge, located in the Arctic basin under the Arctic Ocean ice canopy. We acquired
      this data using hull-mounted sonars attached to a nuclear-powered submarine, the
      USS Hawkbill. Sidescan data for the ultraslow-spreading (approximately 1.0 cm yr(
      1)) eastern Gakkel ridge depict two young volcanoes covering approximately 720
      km2 of an otherwise heavily sedimented axial valley. The western volcano
      coincides with the average location of epicentres for more than 250 teleseismic
      events detected in 1999, suggesting that an axial eruption was imaged shortly
      after its occurrence. These findings demonstrate that eruptions along the
      ultraslow-spreading Gakkel ridge are focused at discrete locations and appear to
      be more voluminous and occur more frequently than was previously thought.

PMID- 11236992
TI  - Our genome unveiled.

PMID- 11236993
TI  - The maps. Clone by clone by clone.

PMID- 11236994
TI  - The draft sequences. Filling in the gaps.

PMID- 11236995
TI  - The draft sequences. Comparing species.

PMID- 11236996
TI  - Single nucleotide polymorphisms. From the evolutionary past...

PMID- 11236998
TI  - Guide to the draft human genome.
AB  - There are a number of ways to investigate the structure, function and evolution
      of the human genome. These include examining the morphology of normal and
      abnormal chromosomes, constructing maps of genomic landmarks, following the
      genetic transmission of phenotypes and DNA sequence variations, and
      characterizing thousands of individual genes. To this list we can now add the
      elucidation of the genomic DNA sequence, albeit at 'working draft' accuracy. The
      current challenge is to weave together these disparate types of data to produce
      the information infrastructure needed to support the next generation of
      biomedical research. Here we provide an overview of the different sources of
      information about the human genome and how modern information technology, in
      particular the internet, allows us to link them together.

PMID- 11236997
TI  - To a future of genetic medicine.

PMID- 11236999
TI  - Mining the draft human genome.
AB  - Now that the draft human genome sequence is available, everyone wants to be able
      to use it. However, we have perhaps become complacent about our ability to turn
      new genomes into lists of genes. The higher volume of data associated with a
      larger genome is accompanied by a much greater increase in complexity. We need to
      appreciate both the scale of the challenge of vertebrate genome analysis and the
      limitations of current gene prediction methods and understanding.

PMID- 11237000
TI  - Keeping time with the human genome.
AB  - The cloning and characterization of 'clock gene' families has advanced our
      understanding of the molecular control of the mammalian circadian clock. We have
      analysed the human genome for additional relatives, and identified new candidate
      genes that may expand our knowledge of the molecular workings of the circadian
      clock. This knowledge could lead to the development of therapies for treating jet
      lag and sleep disorders, and add to our understanding of the genetic contribution
      of clock gene alterations to sleep and neuropsychiatric disorders. The human
      genome will also aid in the identification of output genes that ultimately
      control circadian behaviours.

PMID- 11237002
TI  - Learning about addiction from the genome.
AB  - Drug addiction can be defined as the compulsive seeking and taking of a drug
      despite adverse consequences. Although addiction involves many psychological and
      social factors, it also represents a biological process: the effects of repeated
      drug exposure on a vulnerable brain. The sequencing of the human and other
      mammalian genomes will help us to understand the biology of addiction by enabling
      us to identify both genes that contribute to individual risk for addiction and
      those through which drugs cause addiction. We illustrate this potential impact by
      searching a draft sequence of the human genome for genes related to
      desensitization of receptors that mediate the actions of drugs of abuse on the
      nervous system.

PMID- 11237001
TI  - Expressing the human genome.
AB  - We have searched the human genome for genes encoding new proteins that may be
      involved in three nuclear gene expression processes: transcription, pre-messenger
      RNA splicing and polyadenylation. A plethora of potential new factors are
      implicated by sequence in nuclear gene expression, revealing a substantial but
      selective increase in complexity compared with Drosophila melanogaster and
      Caenorhabditis elegans. Although the raw genomic information has limitations, its
      availability offers new experimental approaches for studying gene expression.

PMID- 11237003
TI  - A genomic view of immunology.
AB  - The outstanding problems facing immunology are whole system issues: curing
      allergic and autoimmune disease and developing vaccines to stimulate stronger
      immune responses against pathogenic organisms and cancer. We hope that the human
      genome sequence will reveal the molecular checks and balances that ensure both an
      effective immunogenic response against pathogenic microorganisms and a suitably
      tolerogenic response to self antigens and innocuous environmental antigens. Three
      synergistic approaches--sequence homology searches, messenger RNA expression
      profiling on microarrays, and mutagenesis in mice--provide the best opportunities
      to reveal, in the genome sequence, key proteins and pathways for targeting by new
      immunomodulatory treatments.

PMID- 11237004
TI  - A genomic perspective on membrane compartment organization.
AB  - Now that whole genome sequences are available for many eukaryotic organisms from
      yeast to man, we can form broad hypotheses on the basis of the relative expansion
      of protein families. To investigate the molecular mechanisms responsible for the
      organization of membrane compartments, we identified members of the SNARE, coat
      complex, Rab and Sec1 protein families in four eukaryotic genomes. Of these
      families only the Rab family expanded from the unicellular yeast to the
      multicellular fly and worm. All families were expanded in humans, where we find
      35 SNAREs, 60 Rabs and 53 coat complex subunits. In addition, we were able to
      resolve the SNARE class of proteins into four distinct subfamilies.

PMID- 11237005
TI  - Genomics, the cytoskeleton and motility.
AB  - The draft human genome sequence is an important step in cataloguing the molecular
      hardware that supports the processes of life. Here I look at what we have learned
      from the draft sequence about our cytoskeletal and motility systems. Most
      cytoskeletal and motility proteins were discovered previously by biochemical
      isolation, traditional cloning methods or random sequences of complementary DNAs.
      The ongoing challenges of assembling and annotating genes for motor proteins with
      long, fragmented coding sequences emphasize the importance of expert knowledge of
      related proteins and confirmatory evidence from cDNA sequences.

PMID- 11237006
TI  - Can sequencing shed light on cell cycling?
AB  - Every organism must have cells that can replicate indefinitely. Can the draft
      human genome sequence tell us how the cell cycle works and how it evolved? We
      studied two protein families--the cyclins and their partners the cyclin-dependent
      kinases (Cdks)--and a conserved regulatory circuit, the spindle checkpoint.
      Disappointingly, we discovered a few novel cyclins and no new Cdks or components
      of the spindle checkpoint, and could shed little light on the organization of the
      cell cycle.

PMID- 11237007
TI  - Evolutionary analyses of the human genome.
AB  - The completion of the human genome will greatly accelerate the development of a
      new branch of science--evolutionary genomics. We can now directly address
      important questions about the evolutionary history of human genes and their
      regulatory sequences. Computational analyses of the human genome will reveal the
      number of genes and repetitive elements, the extent of gene duplication and
      compositional heterogeneity in the human genome, and the extent of domain
      shuffling and domain sharing among proteins. Here we present some first glimpses
      of these features.

PMID- 11237008
TI  - Cancer and genomics.
AB  - Identification of the genes that cause oncogenesis is a central aim of cancer
      research. We searched the proteins predicted from the draft human genome sequence
      for paralogues of known tumour suppressor genes, but no novel genes were
      identified. We then assessed whether it was possible to search directly for
      oncogenic sequence changes in cancer cells by comparing cancer genome sequences
      against the draft genome. Apparently chimaeric transcripts (from oncogenic fusion
      genes generated by chromosomal translocations, the ends of which mapped to
      different genomic locations) were detected to the same degree in both normal and
      neoplastic tissues, indicating a significant level of false positives. Our
      experiment underscores the limited amount and variable quality of DNA sequence
      from cancer cells that is currently available.

PMID- 11237009
TI  - Human disease genes.
AB  - The complete human genome sequence will facilitate the identification of all
      genes that contribute to disease. We propose that the functional classification
      of disease genes and their products will reveal general principles of human
      disease. We have determined functional categories for nearly 1,000 documented
      disease genes, and found striking correlations between the function of the gene
      product and features of disease, such as age of onset and mode of inheritance. As
      knowledge of disease genes grows, including those contributing to complex traits,
      more sophisticated analyses will be possible; their results will yield a deeper
      understanding of disease and an enhanced integration of medicine with biology.

PMID- 11237010
TI  - Computational comparison of two draft sequences of the human genome.
AB  - We are in the enviable position of having two distinct drafts of the human genome
      sequence. Although gaps, errors, redundancy and incomplete annotation mean that
      individually each falls short of the ideal, many of these problems can be
      assessed by comparison. Here we present some comparative analyses of these
      drafts. We look at a number of features of the sequences, including sequence
      gaps, continuity, consistency between the two sequences and patterns of DNA
      binding protein motifs.

PMID- 11237012
TI  - Experimental annotation of the human genome using microarray technology.
AB  - The most important product of the sequencing of a genome is a complete, accurate
      catalogue of genes and their products, primarily messenger RNA transcripts and
      their cognate proteins. Such a catalogue cannot be constructed by computational
      annotation alone; it requires experimental validation on a genome scale. Using
      'exon' and 'tiling' arrays fabricated by ink-jet oligonucleotide synthesis, we
      devised an experimental approach to validate and refine computational gene
      predictions and define full-length transcripts on the basis of co-regulated
      expression of their exons. These methods can provide more accurate gene numbers
      and allow the detection of mRNA splice variants and identification of the tissue-
      and disease-specific conditions under which genes are expressed. We apply our
      technique to chromosome 22q under 69 experimental condition pairs, and to the
      entire human genome under two experimental conditions. We discuss implications
      for more comprehensive, consistent and reliable genome annotation, more
      efficient, full-length complementary DNA cloning strategies and application to
      complex diseases.

PMID- 11237011
TI  - Initial sequencing and analysis of the human genome.
AB  - The human genome holds an extraordinary trove of information about human
      development, physiology, medicine and evolution. Here we report the results of an
      international collaboration to produce and make freely available a draft sequence
      of the human genome. We also present an initial analysis of the data, describing
      some of the insights that can be gleaned from the sequence.

PMID- 11237013
TI  - A map of human genome sequence variation containing 1.42 million single
      nucleotide polymorphisms.
AB  - We describe a map of 1.42 million single nucleotide polymorphisms (SNPs)
      distributed throughout the human genome, providing an average density on
      available sequence of one SNP every 1.9 kilobases. These SNPs were primarily
      discovered by two projects: The SNP Consortium and the analysis of clone overlaps
      by the International Human Genome Sequencing Consortium. The map integrates all
      publicly available SNPs with described genes and other genomic features. We
      estimate that 60,000 SNPs fall within exon (coding and untranslated regions), and
      85% of exons are within 5 kb of the nearest SNP. Nucleotide diversity varies
      greatly across the genome, in a manner broadly consistent with a standard
      population genetic model of human history. This high-density SNP map provides a
      public resource for defining haplotype variation across the genome, and should
      help to identify biomedically important genes for diagnosis and therapy.

PMID- 11237016
TI  - A physical map of the human Y chromosome.
AB  - The non-recombining region of the human Y chromosome (NRY), which comprises 95%
      of the chromosome, does not undergo sexual recombination and is present only in
      males. An understanding of its biological functions has begun to emerge from DNA
      studies of individuals with partial Y chromosomes, coupled with molecular
      characterization of genes implicated in gonadal sex reversal, Turner syndrome,
      graft rejection and spermatogenic failure. But mapping strategies applied
      successfully elsewhere in the genome have faltered in the NRY, where there is no
      meiotic recombination map and intrachromosomal repetitive sequences are abundant.
      Here we report a high-resolution physical map of the euchromatic, centromeric and
      heterochromatic regions of the NRY and its construction by unusual methods,
      including genomic clone subtraction and dissection of sequence family variants.
      Of the map's 758 DNA markers, 136 have multiple locations in the NRY, reflecting
      its unusually repetitive sequence composition. The markers anchor 1,038 bacterial
      artificial chromosome clones, 199 of which form a tiling path for sequencing.

PMID- 11237014
TI  - A physical map of the human genome.
AB  - The human genome is by far the largest genome to be sequenced, and its size and
      complexity present many challenges for sequence assembly. The International Human
      Genome Sequencing Consortium constructed a map of the whole genome to enable the
      selection of clones for sequencing and for the accurate assembly of the genome
      sequence. Here we report the construction of the whole-genome bacterial
      artificial chromosome (BAC) map and its integration with previous landmark maps
      and information from mapping efforts focused on specific chromosomal regions. We
      also describe the integration of sequence data with the map.

PMID- 11237015
TI  - The physical maps for sequencing human chromosomes 1, 6, 9, 10, 13, 20 and X.
AB  - We constructed maps for eight chromosomes (1, 6, 9, 10, 13, 20, X and
      (previously) 22), representing one-third of the genome, by building landmark
      maps, isolating bacterial clones and assembling contigs. By this approach, we
      could establish the long-range organization of the maps early in the project, and
      all contig extension, gap closure and problem-solving was simplified by
      containment within local regions. The maps currently represent more than 94% of
      the euchromatic (gene-containing) regions of these chromosomes in 176 contigs,
      and contain 96% of the chromosome-specific markers in the human gene map. By
      measuring the remaining gaps, we can assess chromosome length and coverage in
      sequenced clones.

PMID- 11237017
TI  - A high-resolution map of human chromosome 12.
AB  - Our sequence-tagged site-content map of chromosome 12 is now integrated with the
      whole-genome fingerprinting effort. It provides accurate and nearly complete
      bacterial clone coverage of chromosome 12. We propose that this integrated
      mapping protocol serves as a model for constructing physical maps for entire
      genomes.

PMID- 11237018
TI  - A physical map of human chromosome 14.
AB  - We report the construction of a tiling path of around 650 clones covering more
      than 99% of human chromosome 14. Clone overlap information to assemble the map
      was derived by comparing fully sequenced clones with a database of clone end
      sequences (sequence tag connector strategy). We selected homogeneously
      distributed seed points using an auxiliary high-resolution radiation hybrid map
      comprising 1,895 distinct positions. The high long-range continuity and low
      redundancy of the tiling path indicates that the sequence tag connector approach
      compares favourably with alternative mapping strategies.

PMID- 11237019
TI  - Integration of telomere sequences with the draft human genome sequence.
AB  - Telomeres are the ends of linear eukaryotic chromosomes. To ensure that no large
      stretches of uncharacterized DNA remain between the ends of the human working
      draft sequence and the ends of each chromosome, we would need to connect the
      sequences of the telomeres to the working draft sequence. But telomeres have an
      unusual DNA sequence composition and organization that makes them particularly
      difficult to isolate and analyse. Here we use specialized linear yeast artificial
      chromosome clones, each carrying a large telomere-terminal fragment of human DNA,
      to integrate most human telomeres with the working draft sequence. Subtelomeric
      sequence structure appears to vary widely, mainly as a result of large
      differences in subtelomeric repeat sequence abundance and organization at
      individual telomeres. Many subtelomeric regions appear to be gene-rich, matching
      both known and unknown expressed genes. This indicates that human subtelomeric
      regions are not simply buffers of nonfunctional 'junk DNA' next to the molecular
      telomere, but are instead functional parts of the expressed genome.

PMID- 11237020
TI  - Comparison of human genetic and sequence-based physical maps.
AB  - Recombination is the exchange of information between two homologous chromosomes
      during meiosis. The rate of recombination per nucleotide, which profoundly
      affects the evolution of chromosomal segments, is calculated by comparing genetic
      and physical maps. Human physical maps have been constructed using cytogenetics,
      overlapping DNA clones and radiation hybrids; but the ultimate and by far the
      most accurate physical map is the actual nucleotide sequence. The completion of
      the draft human genomic sequence provides us with the best opportunity yet to
      compare the genetic and physical maps. Here we describe our estimates of female,
      male and sex-average recombination rates for about 60% of the genome.
      Recombination rates varied greatly along each chromosome, from 0 to at least 9
      centiMorgans per megabase (cM Mb(-1)). Among several sequence and marker
      parameters tested, only relative marker position along the metacentric
      chromosomes in males correlated strongly with recombination rate. We identified
      several chromosomal regions up to 6 Mb in length with particularly low (deserts)
      or high (jungles) recombination rates. Linkage disequilibrium was much more
      common and extended for greater distances in the deserts than in the jungles.

PMID- 11237022
TI  - Labs and companies seek their niches as work continues after the draft.

PMID- 11237023
TI  - Current role suggests the shape of future work opportunities.

PMID- 11237024
TI  - Ultrasound effects on photochemical reactions, part 1: photochemical reactions of
      ketones with alkenes.
AB  - Ultrasound considerably enhances and simplifies photochemical reaction of
      cyclohexanone with cyclohexene. The Paterno-Buchi reaction of acetone with ethyl
      vinyl ether is enhanced by ultrasound and yields a different ratio of cis/trans
      oxetanes under sonication by comparison with the silent reaction. Sonication
      appears to affect the first reaction by homogenization of excited intermediates
      and by quenching the excited triplet state at the second reaction.

PMID- 11237021
TI  - Integration of cytogenetic landmarks into the draft sequence of the human genome.
AB  - We have placed 7,600 cytogenetically defined landmarks on the draft sequence of
      the human genome to help with the characterization of genes altered by gross
      chromosomal aberrations that cause human disease. The landmarks are large-insert
      clones mapped to chromosome bands by fluorescence in situ hybridization. Each
      clone contains a sequence tag that is positioned on the genomic sequence. This
      genome-wide set of sequence-anchored clones allows structural and functional
      analyses of the genome. This resource represents the first comprehensive
      integration of cytogenetic, radiation hybrid, linkage and sequence maps of the
      human genome; provides an independent validation of the sequence map and
      framework for contig order and orientation; surveys the genome for large-scale
      duplications, which are likely to require special attention during sequence
      assembly; and allows a stringent assessment of sequence differences between the
      dark and light bands of chromosomes. It also provides insight into large-scale
      chromatin structure and the evolution of chromosomes and gene families and will
      accelerate our understanding of the molecular bases of human disease and cancer.

PMID- 11237025
TI  - Influence of ultrasound on the kinetic parameters of electrochemical redox
      reactions.
AB  - The aim of this work is to determine the Tafel parameters with and without
      ultrasound. The total overvoltage has been corrected for diffusion by using
      rotating disk technique and potentiostatic extrapolation to infinite rotating
      speed. Three well known redox systems have been selected regardless to their
      different electrochemical behaviour: the quinone-hydroquinone, the Fe(II)Fe(III)
      chlorides and Fe(II)-Fe(III) cyanide systems. This work shows that the
      reversibility is higher with ultrasound only in the case of the quinone
      hydroquinone system.

PMID- 11237026
TI  - A study on the effect of ultrasound on electrochemical phenomena.
AB  - We have employed microelectrodes in order to resolve single transient cavitation
      events. High time resolution studies of individual current time transients were
      shown. Distance and temperature dependencies proved to be in agreement with both
      the acoustic pressure field generated by the ultrasonic horn and cavitation
      bubble collapse violence with decreasing vapour pressure within the bubble,
      respectively. Measurements of electrode kinetics at the point of impact of the
      transient events were shown for the first time by the employment of sampled
      voltammetry.

PMID- 11237027
TI  - Sonoelectrochemical analysis of trace metals.
AB  - Ultrasonically-enhanced mass transport was exploited to increase preconcentration
      efficiency in anodic stripping voltammetry. We developed a Nafion-coated mercury
      thin-film working electrode which is stable under ultrasonic irradiation, making
      it possible to achieve very low limits of detection for relatively short
      preconcentration times. This allows the investigation of a variety of biological
      and environmental samples.

PMID- 11237028
TI  - Sonoelectrochemical determination of nucleosides and nucleotides.
AB  - We summarize our recent work on sonovoltammetric studies of adenine, guanine,
      thymine, cytosine and their corresponding nucleosides and nucleotides. Ultrasound
      is found to be an excellent tool to enhance the reliability of determinations of
      purine and pyrimidine derivatives and can lead to improved analytical performance
      characteristics and lower detection limits.

PMID- 11237029
TI  - The influence of frequency on the mechanical and radical effects for the
      ultrasonic degradation of dextranes.
AB  - The ratio of mechanical and radical effects for the ultrasonic degradation of
      dextranes in aqueous solutions was studied in dependence of frequency and
      molecular weight of the dextranes. For low ultrasound frequency (35 kHz) a
      stronger increase of the polymer degradation with increasing molecular weight was
      found as expected on the basis of the radicals present. This is due to the
      mechanical effects of ultrasound. Applying higher frequencies (>500 kHz) only
      radical reactions are responsible for the degradation. Below a molecular weight
      limit of 40000 the mechanical effects vanish.

PMID- 11237032
TI  - Chrome tannage using high-intensity ultrasonic field.
AB  - The process time in chrome tannage in leather making, using an elastic
      compression cycle followed by irradiation by high-intensity ultrasound, is quite
      short lasting only a few minutes, compared with a process time of several hours
      in modern chrome tannage. After ultrasonic irradiation, samples were basified in
      17 h in chrome liquor at a pH of 4.0 and the shrinkage temperature was measured.
      The determination of the efficiency for the chrome liquor penetrating into the
      hides can be based on the steepness of the shrinkage temperature-processing time
      curve. An approximate value of 20 degrees C min(-1) can be evaluated for the
      initial slope of the curve when elastic compression and high-intensity ultrasonic
      irradiation is used, and a processing time of 2 min is required in chrome liquor
      (plus 17 h basification and 24 h storage time) to obtain leather stable to
      boiling. Usually, hides are kept in chrome liquor for 2 h.

PMID- 11237030
TI  - Comparison of conventional and ultrasonically assisted extractions of
      pharmaceutically active compounds from Salvia officinalis.
AB  - Conventional as well as ultrasonically assisted extractions of biologically
      active compounds from Salvia officinalis using 65% ethanol have been studied.
      Cineole, Thujone and Borneol were used as standards for the GLC-MS evaluation of
      the extracts. The effect of temperature, stirring and mode of sonication
      (ultrasonic bath or horn system) have been studied. The results indicate that
      ultrasonically assisted extraction with mechanical stirring at room temperature
      in a period of 12 h produces a substantial improvement over conventional
      methodology.

PMID- 11237031
TI  - The use of ultrasound for the extraction of bioactive principles from plant
      materials.
AB  - The paper presents our results concerning the ultrasonically assisted extraction
      of bioactive principles from plant material. A comparison with classical
      methodologies is presented and technological aspects of ultrasonically assisted
      extraction are discussed.

PMID- 11237033
TI  - Sonochemical degradation of ethylbenzene in aqueous solution: a product study.
AB  - The degradation of ethylbenzene in aqueous solution by 520 kHz ultrasound was
      investigated. The products formed were analysed using solid phase microextraction
      (SPME), a sampling technique that allows convenient GC-MS and GC-FID analysis in
      the micromolar range. A broad range of monosubstituted monocyclic and dicyclic
      aromatic hydrocarbons was found as well as some oxygenated products. The results
      clearly indicate that pyrolysis is an important pathway of ethylbenzene
      degradation. The side chain is dehydrogenated, forming styrene, or cleaved. The
      radicals formed upon cleavage are subsequently added to the double bond of the
      styrene side chain or recombined. This mechanism explains the formation of most
      of the products. Formation and breakdown of the reaction products follow first
      order kinetics in spite of the fact that the selectivity of the reactions depends
      on the initial ethylbenzene concentration considerably. Changes in the
      temperature and the pressure of cavitation are expected to cause this dependence.

PMID- 11237034
TI  - An investigation into the ultrasonic treatment of polluted solids.
AB  - Granular pieces of brick impregnated with copper oxide were used as a model for
      contaminated soil. Washing this model substrate by passing water across the
      substrate on an ultrasonically shaken tray irradiation afforded a 40% reduction
      in copper content. This was compared with only a 6% reduction when the sample was
      treated under otherwise identical conditions but using a tray shaken
      conventionally. The majority of the copper was removed as a result of the removal
      of surface materials which were more heavily contaminated with the copper oxide.

PMID- 11237035
TI  - The development and evaluation of ultrasound in the biocidal treatment of water.
AB  - The effect of ultrasound upon the destruction of micro-organisms has been studied
      and reported here. The results obtained from the work carried out has shown that
      ultrasound can be used effectively for water disinfection and has several
      advantages. When used in conjunction with chlorine it significantly reduces the
      number of bacteria present in water samples. Ultrasound also reduces the amount
      of chlorine required for disinfection. Increasing the power of ultrasound leads
      to greater efficiency in the destruction of bacterial cells. High frequency
      ultrasound is more beneficial than low frequency in the disinfection of water.

PMID- 11237036
TI  - Measurement of radical production as a result of cavitation in medical ultrasound
      fields.
AB  - This paper describes the use of the terephthalate dosimeter to measure the
      threshold and extent of cavitation arising from medical ultrasound sources at
      high frequencies. Significant hydroxyl radical production was noted from a
      physiotherapy source and low level activity was also detected when using a
      pulsed, diagnostic type transducer system. The effect of sound intensity and the
      type of field is described. The possibility of using polymer degradation to
      monitor the cavitation is also discussed.

PMID- 11237037
TI  - Development and investigation of ultrasound linear phased arrays for transrectal
      treatment of prostate.
AB  - We used the rectangular radiator method as a numerical solution to the Rayleigh
      Sommerfeld diffraction integral for calculating the acoustic fields produced by
      linear arrays. The appropriate phases and amplitudes of voltages applied to the
      elements were computed using the pseudo-inverse method. We have developed and
      acoustically evaluated several constructions of planar linear ultrasound phased
      arrays for transrectal thermotherapy of prostate diseases. The designs of the
      linear phased arrays used in this work were the result of compromise in terms of
      the choice of frequency and number and size of elements, in order to investigate
      a means of improving array performance which might lead to increased efficacy and
      safety of the thermal treatment. The results obtained are in agreement with the
      data of other studies and show that a linear plane phased array may be
      potentially useful for thermal therapy.

PMID- 11237038
TI  - Prostatic tissue ablation by transrectal high intensity focused ultrasound:
      histological impact and clinical application.
AB  - In a phase-I clinical trial the morphologic impact and safety of high-intensity
      focused ultrasound (HIFU) administered transrectally for tissue ablation in human
      prostates (n = 54) was evaluated. Location and size of the tissue lesions
      correlated well with the predefined target area and revealed sharply delineated
      coagulative necrosis in all cases. Intervening tissues, such as the rectal wall
      and posterior prostate capsule were invariably intact. In a subsequent phase-II
      clinical trial safety and efficacy of transrectal HIFU as a novel minimally
      invasive treatment modality for patients with symptomatic benign prostatic
      hyperplasia (BPH; n = 102) was determined. The maximum urinary flow rate (Qmax,
      ml/s) increased from 9.1+/-4.0 to 12.9+/-6.1 (3 months, n=86), 12.7+/-5.1 (6
      months, n=78) and 13.3+/-6.1 (12 months, n=56). In the same time period the post
      void residual volume (ml) decreased from 131+/-115 to 46+/-45, 57+/-46 and 48+/
      36 and the AUA symptom score decreased from 24.5+/-4.7 to 13.3+/-4.4, 13.4+/-4.7
      and 10.8+/-2.5. A subset of patients (n=30) underwent multichannel pressure flow
      studies, which demonstrated that transrectal HIFU reduces bladder outflow
      obstruction. These data demonstrate that transrectal HIFU is capable of inducing
      coagulative necrosis in the human prostate via a transrectal approach while
      preserving intervening and adjacent tissue. A 48% improvement of uroflow and a
      53% decrease of urinary symptoms 1 year after treatment prove that transrectal
      HIFU is an effective and safe minimally invasive treatment option for BPH.

PMID- 11237039
TI  - Targeted damage effects of high intensity focused ultrasound (HIFU) on liver
      tissues of Guizhou Province miniswine.
AB  - HIFU can pass through tissues and accurately damage target tissues inside
      organisms. This article reports on the oriented damage effects of HIFU upon
      miniswine internal and external liver tissues, and suggests a new conception of
      the 'biological focal field'. The results revealed that: (1) HIFU can be used to
      damage accurately liver tissues under the guide of a B-modal ultrasound device;
      (2) the scope of the injury is connected with sound intensity and irradiation
      time; and (3) the different layers of tissue through which the ultrasound has
      passed remain undamaged.

PMID- 11237040
TI  - Sonochemistry in China.
AB  - A comprehensive review of the studies on sonochemistry carried out in China over
      the last 10 years or so is presented and includes 71 references. The studies
      involve both the fundamentals and applications of ultrasound in a variety of
      areas which include polymer science, organic synthesis, chemical analysis,
      biochemistry, the extraction and isolation of natural materials, regeneration of
      waste ion-exchange resins and charcoal, plating and crystallization processes.

PMID- 11237041
TI  - Ultrasound and polar homogeneous reactions.
AB  - The effect of ultrasound on the rates of homogeneous heterolytic reactions not
      switched to a free radical pathway can be explained by the perturbation of the
      molecular organization of or the solvation in the reacting system. A quantitative
      analysis of the sonochemical acceleration on the basis of the microreactor
      concept was carried out. It was found that (1) the Diels-Alder reaction cannot be
      accelerated by ultrasound except when SET or free radical processes are promoted,
      (2) the rectified diffusion during cavitation cannot be responsible for the
      acceleration of reactions, and (3) the sonochemical acceleration of polar
      homogeneous reactions takes place in the bulk reaction medium. This implies the
      presence of a 'sound-field' sonochemistry besides the 'hot-spot' sonochemistry.
      The occurrence of a sonochemical deceleration effect can be predicted.

PMID- 11237042
TI  - Kinetics of nitrous acid formation in nitric acid solutions under the effect of
      power ultrasound.
AB  - Sonochemical nitrous acid formation was investigated in 0.1-4.0 mol dm(-3)
      aqueous nitric acid solutions under the effect of power ultrasound with 20 kHz
      frequency. HNO2 steady-state concentration was obtained under long-time
      sonication; the excess HNO2 formed is decomposed and evoluted from the solution
      as NO and NO2 gases. The HNO2 steady-state concentration and the HNO2 initial
      formation rate depend linearly on the HNO3 concentration and acoustic intensity
      (1.8-3.5 W cm(-2)) and decrease with rising temperature in the range 21-50
      degrees C. The HNO2 formation rate depends on the type of saturating gas as
      follows: Ar > N2 > He > air. NO and O2 are the major gaseous products of HNO3
      sonication. The NO2 accumulation of in the gas phase is observed only when the
      decomposition of HNO2 formed becomes noticeable. The gaseous products formation
      rates depend on the HNO3 concentration, acoustic intensity and the type of
      saturating gas. The mechanism of HNO2 sonochemical formation is assumed to be the
      thermal decomposition of HNO3 in the gaseous vicinity of collapsing bubbles or in
      the overheated liquid reaction zone surrounding the cavitational bubbles.

PMID- 11237043
TI  - On the frequency and isotope effect in sonochemistry.
AB  - In the first part of the work, it was observed, by a relative method, that the
      Weissler reaction and the Br2-catalysed isomerisation of maleic acid into fumaric
      acid are faster at 20 kHz than at 1.7 MHz. The difference between the relative
      reaction rates can be considered as small when the two order magnitude difference
      between the two frequencies is taking into account. In the second part of the
      work, the frequency effect associated to an isotope effect was studied. The
      Weissler reaction was performed in H2O and D2O at 20 kHz and 1.7 MHz. The isotope
      effect is not the same at the two frequencies.

PMID- 11237044
TI  - A few questions on the sonochemistry of solutions.
AB  - Sonochemical reactions in solution have an underexploited synthetic potential.
      Most of the obstacles to expand this attractive domain come from unanswered
      questions on, for example, the importance of the radiomimetic effect, the
      implication of the solvent as a relay in the reaction mechanism, the existence of
      redox processes, and concerning cavitation, the structure of the bubble interface
      and the pressure effects associated to the collapse.

PMID- 11237045
TI  - The heating phenomenon produced by an ultrasonic fountain.
AB  - When a piece of plastic sheet is placed in the path of an ultrasonic fountain
      generated using a medical nebulizer in water, temperatures of up to 250 degrees C
      can be produced on the face of the sheet opposite the fountain impact. This paper
      describes the experimental methodology and results, and suggests that this
      phenomenon is the combined result of both the heating and mechanical effect of
      ultrasonic cavitation within the fountain.

PMID- 11237046
TI  - Comparisons of sonoluminescence from single-bubbles and cavitation fields:
      bridging the gap.
AB  - Sonoluminescence (SL) refers to the generation of light through the energetic
      pulsations of acoustic cavitation bubbles in a liquid. For years, SL was observed
      primarily in cavitation fields. These bubbles are believed by many to undergo
      near-adiabatic compression, resulting in the heating of the bubble contents and
      the subsequent emission of light. Recently, researchers have discovered a 'new'
      form of sonoluminescence in which light is observed to emanate from a single
      bubble undergoing very large volume excursions. The mechanism for light
      production is unknown, but many believe it is due to a rapid heating of the
      central core by an imploding shock wave. Based in part on the emission time
      scales, there is a common belief that the two forms of SL are quite distinct. We
      address this issue by comparing the two phenomena with regards to their light
      flash durations and emission spectra--leading to some surprising differences and
      similarities.

PMID- 11237047
TI  - Cavitation bubble dynamics.
AB  - The dynamics of cavitation bubbles on water is investigated for bubbles produced
      optically and acoustically. Single bubble dynamics is studied with laser produced
      bubbles and high speed photography with framing rates up to 20.8 million frames
      per second. Examples for jet formation and shock wave emission are given.
      Acoustic cavitation is produced in water in the interior of piezoelectric
      cylinders of different sizes (up to 12 cm inner diameter). The filementary
      structure composed of bubbles is investigated and their light emission
      (sonoluminescence) studied for various driving strengths.

PMID- 11237048
TI  - Modelling of free radicals production in a collapsing gas-vapour bubble.
AB  - This paper deals with a model linking bubble dynamics under an acoustic pressure
      field and production of free radicals in the resulting collapses of this bubble.
      The bubble dynamics model includes interdiffusion of gas and vapour in the bubble
      as well as evaporation or condensation at the interface, and it assumes
      uniformity of the internal pressure and perfect gas law for the gas vapour
      mixture. At the maximum compression of the bubble, all the reactions of
      dissociation which can occur are assumed at thermodynamic equilibrium. The local
      composition (especially in free radicals) in the bubble is then calculated by an
      algorithm based on free energy minimization using the information concerning the
      maximum compression provided by the bubble dynamics model resolution. Using this
      model a comparison of free radicals production has been made for two different
      driving frequencies (20 kHz and 500 kHz), and at given bubble radius and acoustic
      pressure, an optimum of liquid bulk temperature has been derived for the
      production of free radicals very similar to the experimental one concerning
      oxidation reactions in aqueous phase.

PMID- 11237049
TI  - Some comments on the thermodynamics of sonoluminescence--a personal view.
AB  - The path of the gas in a sonoluminescent bubble must enclose an area in a P-V
      plot if the gas itself emits photons. Thermodynamic analysis thus delineates the
      playing field that may enable us to distinguish liquid-phase emissions from gas
      phase emissions. The apparent importance of the van der Waals a (which
      parameterizes mean-square induced dipole attractions) in light intensity supports
      collision-induced emission as a likely mechanism. The suggested emitting object,
      containing 10(10) molecules in picosecond-long van der Waals contact, is novel,
      being neither plasma, gas, liquid nor blackbody. The bubble pursues a unique
      thermodynamic path.

PMID- 11237050
TI  - Ultrasound promoted N-alkylation of pyrrole using potassium superoxide as base in
      crown ether.
AB  - Ultrasound accelerates the N-alkylation of pyrrole by alkylating reagents using
      potassium superoxide as base in the presence of 18-crown-6. A much lower yield of
      N-alkylated pyrrole was realized in the absence of ultrasound. N-alkylating
      reagents employed for pyrrole are methyl iodide, ethyl bromide, benzyl bromide,
      as well as acrylonitrile allyl cyanide and methyl acrylate. In an extension of
      this work, we have found that ultrasound was not necessary for the N-alkylation
      of indole and alkyl amine, such as diphenyl amine and piperidine with alkyl
      halides using our reagents. In all cases we observed that the 18-crown-6
      catalyzed N-alkylation reaction gives higher yields of N-alkylated products than
      that without crown ether, when potassium superoxide was used as base. These
      observations are probably due to the potassium-crown complex which can be
      released when the reaction goes to completion.

PMID- 11237051
TI  - Ultrasound in natural products synthesis: applications to the synthesis of
      histrionicotoxin via nitroalkanal acetals.
AB  - Ultrasound promoted the Kornblum reaction of silver nitrite or sodium nitrite
      with haloalkyl acetals to afford the corresponding C-nitro compounds. The
      acetalprotected nitro compounds were used as reactants in a 'double Henry'
      reaction to produce the key intermediate nitrocyclohexane diol with a masked
      aldehyde side chain. The nitrodiol was then subjected to an ultrasound-promoted
      one-pot/single operation sequence involving a reduction deprotection followed by
      a cyclization-reduction. The entire sequence provided the core spiropiperidine
      substructure of the histrionicotoxins.

PMID- 11237052
TI  - Molecular parasitology goes cellular.
AB  - Application of molecular genetics is an increasingly feasible undertaking in
      parasitology; however, an understanding of the phenotypes of various mutants
      generated by this approach will ultimately rely on cellular approaches to resolve
      the function of various proteins. In addition to the advances in understanding
      the biology of parasitism, such studies probably will uncover fundamental aspects
      of how eukaryotic cells communicate and regulate their responses to the
      environment. Thus, parasites may one day provide useful biological tools, just as
      viruses and bacterial toxins have done in the past, towards probing the biology
      of mammalian cells.

PMID- 11237053
TI  - Transcription factors and translocations in lymphoid and myeloid leukemia.
AB  - Chromosomal translocations involving transcription factors and aberrant
      expression of transcription factors are frequently associated with
      leukemogenesis. Transcription factors are essential in maintaining the regulation
      of cell growth, development, and differentiation in the hematopoietic system.
      Alterations in the mechanisms that normally control these functions can lead to
      hematological malignancies. Further characterization of the molecular biology of
      leukemia will enhance our ability to develop disease-specific treatment
      strategies, and to develop effective methods of diagnosis and prognosis.

PMID- 11237055
TI  - Synergistic activity of the new ABL-specific tyrosine kinase inhibitor STI571 and
      chemotherapeutic drugs on BCR-ABL-positive chronic myelogenous leukemia cells.
AB  - The ABL-specific tyrosine kinase inhibitor STI571 (formerly CGP57148B) induced
      cytogenetic remissions in 33% of chronic myelogenous leukemia (CML) patients in a
      phase I trial (Druker et al 1999). Combination therapy may increase this
      proportion. We tested whether combinations of STI571 and cytarabine or other
      chemotherapeutic agents such as hydroxyurea, mafosfamide or etoposide would
      display synergistic activity in BCR-ABL-positive chronic myelogenous leukemia
      (CML) cell lines derived from patients in blast crisis. In addition, the toxicity
      of these combinations on BCR-ABL-negative cells was investigated. A tetrazolium
      based MTT assay was used to quantity growth inhibition after 48 h of exposure to
      cytotoxic agents alone and in simultaneous combination with STI571. The drug
      interactions were analyzed using the median-effect method of Chou and Talalay.
      The combination index (CI) was calculated according to the classic isobologram
      equation. At growth inhibition levels of over 50%, STI571 + cytarabine as well as
      STI571 + etoposide were significantly synergistic (CI < 1, P < 0.05) in the BCR
      ABL-positive cell lines evaluated. At 60% inhibition or higher, a similar
      synergistic pattern became apparent for STI571 + mafosfamide (P < 0.05), while
      STI571 + hydroxyurea showed ambiguous, cell line-dependent synergism (BV173),
      additivity (EM-3) or antagonism (K562) in CML cell lines. Furthermore, the BCR
      ABL-negative HL-60, KG1a and normal CD34+ progenitor cells were not affected by
      0.8 microM STI571, a concentration which produced more than 50% growth inhibition
      in all BCR-ABL-positive cells tested, and no potentiation of growth inhibition
      was observed in these BCR-ABL-negative cells when STI571 was combined with
      chemotherapeutic agents. Our in vitro data with CML blast crisis cell lines
      strongly suggest that combinations of STI571 with cytarabine or etoposide be
      rapidly considered for clinical testing.

PMID- 11237056
TI  - Idarubicin improves blast cell clearance during induction therapy in children
      with AML: results of study AML-BFM 93. AML-BFM Study Group.
AB  - In the randomized trial AML-BFM 93 we compared 60 mg/m2/day daunorubicin with 12
      mg/m2/day idarubicin for 3 days each, combined with cytarabine and etoposide
      during induction. Results showed a significant better blast cell reduction in the
      bone marrow on day 15 in patients of the idarubicin arm (25 of 144 = 17% of
      patients with > or = 5% blasts compared to 46 of 149 = 31% of patients after
      daunorubicin, Pchi2 = 0.01). This was, however, mainly seen in high risk patients
      treated with idarubicin (19% vs 38%, Pchi2 = 0.007). Cardiotoxicity, WHO grade 1
      3 shortening fraction reduction after induction occurred in 6% patients in both
      arms. Bone marrow toxicity differed slightly with a median recovery time of
      neutrophils >500/microl of 25 days (daunorubicin) compared to 27 days
      (idarubicin), P = 0.05. In the total group of patients probabilities of 5 years
      event-free survival and disease-free survival were similar for patients treated
      with daunorubicin or idarubicin (49% +/- 4% vs 55% +/- 4% and 57% +/- 4% vs 64%
      +/- 4%, P logrank 0.29 and 0.15, respectively). However, in patients presenting
      with more than 5% blasts on day 15 there was a trend for a better outcome after
      treatment with idarubicin (P logrank 0.06). Together with the early effect seen
      for high risk patients these results indicate a better efficacy of idarubicin
      than of daunorubicin during induction with a similar rate of toxicity.

PMID- 11237057
TI  - Treatment of leukemic relapse after allogeneic stem cell transplantation with
      cytotoreductive chemotherapy and/or immunotherapy or second transplants.
AB  - We analyzed toxicity and efficacy of chemotherapy (CT) or second stem cell
      transplantation (SCT) and/or immunotherapy defined as stop of immunosuppression
      (IS) or donor leukocyte infusion (DLI) in 47 patients relapsing with acute
      leukemia. Ten patients received no treatment and 14 patients were treated with CT
      only. In 12 patients IS was stopped and three of them received additional CT.
      Five patients received DLI after CT as consolidation and one patient as frontline
      therapy. Five patients received a second SCT. Median overall survival after
      relapse was 2 months for the untreated patients, 2 months for patients receiving
      CT only, 2 months in patients after cessation of IS, 17 months in DLI treated
      patients and three months in patients receiving a second SCT. Fourteen patients
      achieved remission after relapse. Two with CT (2, 2 months), three with SI (3,
      19, 19+ months), six with DLI (3, 8, 9, 14, 20, 36 months) and three with second
      SCT (2, 4, 6 months). Conventional CT was able do re-establish donor
      hematopoiesis and patients achieving remission showed a significantly better
      survival than patients with refractory disease. Patients who were brought into
      remission by DLI or cessation of IS had a significantly better survival than
      patients who achieved remission with CT alone or a second SCT. We conclude that a
      selected group of patients achieving remission with regeneration of donor
      hematopoiesis following CT might benefit from immunotherapy as consolidation.

PMID- 11237054
TI  - Using death to one's advantage: HIV modulation of apoptosis.
AB  - Infection by human immunodeficiency virus (HIV) is associated with an early
      immune dysfunction and progressive destruction of CD4+ T lymphocytes. This
      progressive disappearance of T cells leads to a lack of immune control of HIV
      replication and to the development of immune deficiency resulting in the
      increased occurrence of opportunistic infections associated with acquired immune
      deficiency syndrome (AIDS). The HIV-induced, premature destruction of lymphocytes
      is associated with the continuous production of HIV viral proteins that modulate
      apoptotic pathways. The viral proteins, such as Tat, Env, and Nef, are associated
      with chronic immune activation and the continuous induction of apoptotic factors.
      Viral protein expression predisposes lymphocytes, particularly CD4+ T cells, CD8+
      T cells, and antigen-presenting cells, to evolve into effectors of apoptosis and
      as a result, to lead to the destruction of healthy, non-infected T cells. Tat and
      Nef, along with Vpu, can also protect HIV-infected cells from apoptosis by
      increasing anti-apoptotic proteins and down-regulating cell surface receptors
      recognized by immune system cells. This review will discuss the validity of the
      apoptosis hypothesis in HIV disease and the potential mechanism(s) that HIV
      proteins perform in the progressive T cell depletion observed in AIDS
      pathogenesis.

PMID- 11237058
TI  - The leukemogenic transcription factor E2a-Pbx1 induces expression of the putative
      N-myc and p53 target gene NDRG1 in Ba/F3 cells.
AB  - The chimeric transcription factor E2a-Pbx1 is expressed as a result of the 1;19
      chromosomal translocation in some 5% of cases of pediatric acute lymphoblastic
      leukemia. We investigated the biological and transcriptional consequences of
      forced expression of E2a-Pbx1 in the interleukin-3 (IL-3) dependent, bone marrow
      derived cell line Ba/F3. We show that forced expression of E2a-Pbx1 induces
      apoptosis in Ba/F3 cells without apparent effects on cell cycle progression. This
      pro-apoptotic effect is enhanced on cytokine deprivation. Furthermore, using cDNA
      representational difference analysis (RDA), we show that these cellular effects
      are associated with marked induction of the gene NDRG1, which was previously
      identified as a target of transcriptional repression by N-myc and induction by
      the tumor suppressor protein p53. We identify a portion of the NDRG1 promoter
      capable of mediating transcriptional induction by E2a-Pbx1 and show that NDRG1 is
      also induced on simple IL-3 deprivation of BaF3 cells. Although we show that E2a
      Pbx1 induction of NDRG1 is not impaired as a result of targeting p53 using HPV
      E6, and therefore does not appear to be p53-dependent, our results overall are
      consistent with the notion that induction of NDRG1 by E2a-Pbx1 may represent part
      of an apoptotic or cytostatic cellular response to oncogene activation.

PMID- 11237059
TI  - Deletion of chromosomal region 13q14.3 in childhood acute lymphoblastic leukemia.
AB  - Deletion of the 13q14 chromosomal region is frequent in B cell chronic
      lymphocytic leukemia (B-CLL) and is believed to inactivate a tumor supressor gene
      (TSG) next to RB1. We studied microsatellite markers spanning the 13q14
      chromosomal region in 138 children with acute lymphoblastic leukemia (ALL).
      Allelic loss was demonstrated in six cases (4.3%). Deletion did not include RB1
      in two cases. In five patients, the deleted region overlapped that described in B
      CLL. A sixth patient harbored a smaller deletion, slightly more telomeric than
      minimal deleted regions reported in B-CLL. Apparent differences in the
      delineation of the minimal deleted region could be due to the fact that the
      putative TSG is a very large gene, with some deletions affecting only a part of
      it. Our present findings suggest that at least some of its exons lie within a
      region of less than 100 kb more telomeric that previously thought.

PMID- 11237060
TI  - Cytogenetic subgroups in acute myeloid leukemia differ in proliferative activity
      and response to GM-CSF.
AB  - The current study was undertaken to search for differences in the biology of
      cytogenetic subgroups in patients with de novo acute myeloid leukemia (AML). In
      addition, factors influencing the metabolism of cytosine arabinoside (araC) as
      the key agent of antileukemic activity were assessed. Bone marrow aspirates from
      91 patients with newly diagnosed AML in whom karyotypes were successfully
      obtained were analyzed: (1) for spontaneous proliferative activity by 3H
      thymidine (3H-TdR) incorporation; (2) proliferative response to GM-CSF by in
      vitro incubation of blasts for 48 h with or without GM-CSF (100 U/ml) followed by
      an additional 4-h exposure to 3H-TdR (0.5 microCi/ml); and (3) parameters of araC
      metabolism comprising 3H-araC uptake in vitro and the activities of polymerase
      alpha (poly alpha), deoxycytidine kinase (DCK) and deoxycytidine deaminase (DCD).
      According to the results of chromosome analyses four cytogenetic subgroups were
      discriminated: (I) normal karyotypes (n = 38); (II) favorable karyotypes [t8;21),
      t(15;17), inv(16)] (n = 16); (III) unfavorable karyotypes [inv (3), -5, 5q-,
      t(6;9), +8, t (9;11), complex abnormalities] (n = 20); (IV) karyotypes of unknown
      prognostic significance (n = 17). Proliferative activity of leukemic blasts was
      significantly higher in favorable karyotypes (group II) as compared to cases with
      unfavorable cytogenetics (group III) with median values and range for 3H-TdR
      uptake in group II of 2.48 pmol/10(5) cells (0.28-25.8) and in group III of 0.51
      pmol/10(5) cells (0.04-7.6) (P = 0.0096). The respective values in group I and
      group IV were 0.7pmol/10(5) cells (0.0-6.7) and 0.98 pmol/10(5) cells (0.0-4.0),
      respectively. Inversely, response to GM-CSF, as defined by an increase in 3H-TdR
      incorporation >1.5- fold over control values after 48h of GM-CSF exposure, was
      significantly lower for patients with a favorable karyotype (group II) as
      compared to group I (P = 0.04) and group III (P = 0.013). No significant
      differences between karyotype groups I, II, III and IV were found for 3H-araC
      incorporation, nor for the activities of poly alpha, DCK and DCD. These data
      demonstrate differences in the biology of cytogenetic subgroups in AML which may
      partly explain the well established differences in clinical outcome.

PMID- 11237061
TI  - Comparison of methods for assessment of minimal residual disease in childhood B
      lineage acute lymphoblastic leukemia.
AB  - The level of minimal residual disease (MRD) early in treatment of acute
      lymphoblastic leukemia (ALL) strongly predicts the risk of marrow relapse. As a
      variety of methods of varying complexity have been separately used for detecting
      and quantifying MRD, we compared the prognostic utility of three methods
      measurement of blast percentage on day 14 of treatment, detection of
      monoclonality on day 14 or day 35, and measurement of MRD by PCR-based limiting
      dilution analysis on day 14 or day 35. The study group comprised 38 children aged
      1-15 with Philadelphia-negative B-lineage ALL who were uniformly treated and
      followed until relapse or for a minimum of 5 years. We also studied some of the
      technical factors which influence the ability to detect MRD. Measurement of blast
      percentage on day 14 by an expert morphologist, detection of monoclonality on day
      35, and PCR-based measurement of MRD levels on days 14 and 35 all showed
      significant ability to divide patients into prognostic groups. Measurement of
      blast percentage on day 14 by routine morphology or detection of monoclonality on
      day 14 were not useful. The quality of DNA samples varied greatly, as determined
      by amplifiability in the PCR. However, virtually all amplifiable leukemic targets
      in a sample were detectable which suggests that the level of detection achieved
      by limiting dilution analysis is essentially determined by the amount of DNA
      which it is practicable to study. We conclude that quantification of MRD at the
      end of induction provides the full range of prognostic information for marrow
      relapse but is complex; detection of monoclonality on day 35 is simple and has
      good positive predictive value; and quantification of MRD on day 14 merits
      further study. PCR-based methods for measurement of MRD levels should incorporate
      a correction for variation in DNA amplifiability.

PMID- 11237062
TI  - The role of AP-1 in glucocorticoid resistance in leukaemia.
AB  - Glucocorticoids are used in the treatment of acute lymphoblastic leukaemia (ALL)
      and chronic lymphocytic leukaemia (CLL) but many patients develop glucocorticoid
      resistance on relapse. The ligand-activated glucocorticoid receptor inhibits
      activity of the AP-1 transcription factor and the purpose of this study was to
      test the hypothesis that up-regulation or overexpression of AP1-binding activity
      may be an important mechanism of glucocorticoid resistance in ALL and CLL. In
      vitro sensitivity of patient blasts to prednisolone was measured using th

PMID- 11237063
TI  - MDR1 expression in poor-risk acute myeloid leukemia with partial or complete
      monosomy 7.
AB  - Expression of the multidrug resistance (MDR1) phenotype, encoded by the MDR1
      gene, is an adverse prognostic factor for CR and survival in acute myeloid
      leukemia (AML). Other prognostic factors, such as specific cytogenetic
      abnormalities, have been identified in AML. We have investigated the expression
      of the MDR1 gene in untreated AML patients with monosomy 7 (n = 12), and partial
      deletions (n = 7) of the long arm of chromosome 7 (respectively -7/7q-), because
      of the extremely bad prognosis associated with these cytogenetic abnormalities
      and because of the fact that the MDR1 gene is located on chromosome 7q21.1. The
      findings were compared with the level of MDR1 expression in a group of 42 other
      AML patients, matched for age with favourable, neutral or complex cytogenetic
      abberations. MDR1 mRNA expression, as measured by the RNase protection assay was
      significantly higher in the -7/7q- group vs other AML patients (median 1.3 vs 0.1
      arbitrary units, P = 0.02). Protein expression of MDR1 in the -7/7q- group, as
      determined with the monoclonal antibody MRK16, was found to be similar to the
      levels found in the control group. With a functional rhodamine retention assay
      using the modulator PSC833, increased MDR1 activity was observed in the -7/7q-
      group as compared to the control group of patients (P = 0.05). Considering the
      higher MDR1 mRNA expression and equal or slightly elevated level of protein
      expression of MDR1, we studied the presence of MDR1 genes in this group of -7/7q-
      patients. Fluorescence in situ hybridization (FISH) studies, using a specific
      MDR1 probe revealed no loss of an MDR1 allele in any of the deleted q- arms of
      the seven patients with 7q-, whereas all monosomy 7 patients lacked one MDR1 gene
      homologue. To determine whether there was selective loss of the MDR1 gene in the 
      7/7q- patients, the genetic polymorphism of the MDR1 gene was used. Both allelic
      variants (G and T) were represented in the -7/7q- and in the control group,
      showing a predominance for GT at position 2677 of the MDR1 gene in the control
      group. In the 12 monosomy 7 patients loss of the MDR1 allele was random.
      Methylation studies of the CpG island of the MDR1 gene revealed no
      hypermethylation in any of the -7/7q- patients. We conclude that MDR1 expression
      in -7/7q- AML patients is upregulated at transcriptional, but not at
      translational level, suggesting that mechanisms other than MDR1 are responsible
      for the poor prognosis in these patients.

PMID- 11237064
TI  - Adult precursor B-ALL with BCR/ABL gene rearrangements displays a unique
      immunophenotype based on the pattern of CD10, CD34, CD13 and CD38 expresssion.
AB  - The Philadelphia chromosome (Ph+) reflects a balanced reciprocal translocation
      between the long arms of chromosomes 9 and 22 [t(9;22)(q34;q11.2] involving the
      BCR and ABL genes. At present, detection of BCR/ABL gene rearrangements is
      mandatory in precursor-B-ALL patients at diagnosis for prognostic stratification
      and treatment decision. In spite of the clinical impact, no screening method,
      displaying a high sensitive and specificity, is available for the identification
      of BCR/ABL+ precursor-B-ALL cases. The aim of the present study was to explore
      the immunophenotypic characteristics of precursor B-ALL cases displaying BCR/ABL
      gene rearrangements using multiple stainings analyzed by quantitative flow
      cytometry in order to rapidly (<1 h) identify unique phenotypes associated with
      this translocation. From the 82 precursor-B-ALL cases included in the study 12
      displayed BCR/ABL gene rearragements, all corresponding to adult patients, four
      of which also displayed DNA aneuploidy. Our results show that BCR/ABL+ precursor
      B-ALL cases constantly displayed a homogeneous expression of CD10 and CD34 but
      low and relatively heterogeneous CD38 expression, together with an aberrant
      reactivity for CD13. In contrast, this unique phenotype was only detected in
      three out of 70 BCR/ABL cases. Therefore, the combined use of staining patterns
      for CD34, CD38 and CD13 expression within CD10-positive blast cells is highly
      suggestive of BCR/ABL gene rearrangements in adults with precursor B-ALL.

PMID- 11237065
TI  - Screening for herpesvirus genomes in common acute lymphoblastic leukemia.
AB  - There is epidemiological evidence that infection may play a role in the etiology
      of childhood leukemia in particular common B cell precursor acute lymphoblastic
      leukemia. A panel of 20 leukemic samples (panel 1) was examined for the presence
      of four lymphotropic herpesviruses using conventional molecular techniques. A
      second independent panel of 27 leukemic samples (panel 2), along with 28 control
      peripheral blood samples from children with other forms of cancer, was tested for
      the presence of the same four viruses using sensitive real-time quantitative PCR.
      While herpesvirus genomes were detected, they were present at very low levels;
      detection rates and levels were similar in the leukemic and control panels. In
      addition we surveyed 18 leukemic samples (five from panel 1, six from panel 2 and
      a further seven samples not previously analyzed) using a degenerate PCR assay
      capable of detecting the genomes of known herpesviruses plus putative new members
      of the family. No novel herpesvirus genomes were detected suggesting that a
      herpesvirus is unlikely to be etiologically involved as a transforming agent in
      common acute lymphoblastic leukemia.

PMID- 11237066
TI  - Growth advantage of chronic myeloid leukemia CFU-GM in vitro: survival to growth
      factor deprivation, possibly related to autocrine stimulation, is a more common
      feature than hypersensitivity to GM-CSF/IL3 and is efficiently counteracted by
      retinoids +- alpha-interferon.
AB  - Bcr/abl fusion gene, in experimental models, induces survival to growth factor
      deprivation and hypersensitivity to IL3. However, conflicting data were reported
      about chronic myeloid leukemia (CML) progenitors. We investigated the
      responsiveness of purified CML CFU-GM to GM-CSF/IL3 and their survival to growth
      factor deprivation. CFU-GM hypersensitivity to IL3 and/or GM-CSF was found in
      3/11 CML cases only. CML CFU-GM survived well in stroma-free 'mass' culture (5 x
      10(4) cells/ml) without cytokine addition, up to day 11, average recovery being
      around 95% in medium + 10% fetal bovine serum and 67-81% in serum-free medium.
      Conversely, normal progenitors declined steadily, particularly after extensive
      purification (18 +/- 10% recovery at the 7th day), and in serum-free medium (4 +/
      6% recovery). By contrast, normal and CML CFU-GM declined in a similar way in
      limiting dilution cultures (1-10 cells/50 microl). We also investigated the
      effects of retinoic acid and alpha-interferon on CFU-GM survival. Both all-trans-
      and 13-cis retinoic acid, particularly in combination with alpha-interferon,
      reduced CML CFU-GM recovery down to normal progenitors' values. In conclusion,
      hypersensitivity to CSFs is rare in CML, whereas resistance to growth factor
      deprivation has been confirmed in mass, but not in limiting, dilution cultures.
      Both stereoisomers of retinoic acid, at therapeutic concentrations and in
      combination with alpha-interferon, can overcome the survival advantage of CML
      progenitors.

PMID- 11237067
TI  - Sequential analysis of CD34+ and CD34- cell subsets in peripheral blood and
      leukapheresis products from breast cancer patients mobilized with SCF plus G-CSF
      and cyclophosphamide.
AB  - Administration of stem cell factor (SCF) has been proven to enhance cytokine
      induced mobilization of CD34+ hematopoietic progenitor cells (HPC) into the
      peripheral blood (PB). The aim of the present study was to explore in a
      homogeneous group of 22 uniformly treated breast cancer patients: (1) the
      kinetics of mobilization into PB of both CD34+ and CD34- cell subsets, including
      dendritic cells, in sequential samples obtained from day +7 up to day +12 after
      mobilization; and (2) the composition of the CD34+ and CD34- cell subsets present
      in the two leukapheresis products obtained for each patient. The following CD34+
      and CD34- subsets were analyzed: early CD34+ HPC, erythroid-, myeloid- and B
      lymphoid-committed CD34+ precursor cells, mature T, B and NK cells, monocytes,
      neutrophils, eosinophils, basophils, and dendritic cells (DC) including three
      subsets of lin-/HLADR+DC (CD16+, CD33high and CD123high). Our results show that
      the absolute number of PB CD34+ HPC progressively increases from day +7 onwards.
      As far as the CD34- PB leukocyte subsets are concerned, monocytes (CD14+)
      displayed the earliest recovery after mobilization predicting neutrophil recovery
      1 day in advance. The number of CD34+ HPC collected in a single leukapheresis
      product was always > or = 1.4 x 10(6) cells/kg body weight. No significant
      changes were observed between the two leukapheresis sessions either as regards
      their composition in CD34+ HPC subsets or their CD34- leukocyte populations
      except for a higher ratio of both CD34+ erythroid/CD34+ myeloid HPC (0.35 +/-
      0.13 vs 0.30 +/- 0.13; P = 0.04) and neutrophils/monocytes (1.58 +/- 2.1 vs 0.69
      +/- 0.27; P = 0.009) found for the first leukapheresis. Interestingly, the
      overall number of dendritic cells (DC) was higher in the second leukapheresis
      (1.06 +/- 0.56 vs 1.9 +/- 0.46; P = 0.02) due to a selective increase of the
      CD16+ antigen-presenting cells. In summary, our results show that the combination
      of cyclophosphamide, G-CSF and SCF is highly effective for stem cell
      mobilization, with differences observed in the mobilization kinetics of the
      different hematopoietic cell subsets analyzed.

PMID- 11237068
TI  - Reversible erythrocyte skeleton destabilization is modulated by beta-spectrin
      phosphorylation in childhood leukemia.
AB  - The erythrocyte skeleton plays an essential role in determining the shape and
      deformability of the red cell. Disruption of the interaction between components
      of the red cell membrane skeleton may cause loss of structural and functional
      integrity of the membrane. Several observations based on studies in vitro
      strongly suggest that phosphorylation may modify interactions between proteins,
      leading to a reduced affinity. In particular, increased phosphorylation of beta
      spectrin decreases membrane mechanical stability. In order to investigate the
      presence of membrane protein defects we investigated the erythrocyte membrane
      protein composition and phosphorylation in 22 children with leukemia at diagnosis
      and during the remission phase. Sixteen children had acute lymphoblastic leukemia
      (ALL), three had chronic myeloid leukemia (CML) and three had acute myeloid
      leukemia (AML). Ten patients (eight ALL and two CML) displayed elliptocytosis and
      poikilocytosis, an increase of spectrin dimers (41.8 +/- 15.6) and an enhanced
      phosphorylation of beta-spectrin (108 +/- 15%) at diagnosis. These alterations
      disappeared during the remission phase. This is the first demonstration of a
      reversible erythrocyte membrane alteration in leukemia. Since the beta-spectrin
      phosphate sites are located near the C-terminal region and close to the head of
      the beta-chain that is involved in dimer-dimer interaction, we supposed that the
      beta-chain phosphorylation has an effect upon the interactions between spectrin
      dimers, ie the tetramerization process. The weakening of this process should be
      responsible for the presence of elliptocytes and poikilocytes as reported in
      hereditary elliptocytosis and pyropoikilocytosis.

PMID- 11237069
TI  - Stem cell transplantation for chronic lymphocytic leukemia: different outcome
      after autologous and allogeneic transplantation and correlation with minimal
      residual disease status.
AB  - The clinical outcome and its correlation with the status of minimal residual
      disease (MRD) was analyzed in 26 patients with chronic lymphocytic leukemia (CLL)
      undergoing stem cell transplantation. All patients having received autotransplant
      (n = 14) achieved CR which was MRD(-) in nine patients (64%) and MRD(+) in five.
      With a median follow-up of 26.5 months (range, 12-52), four of the five MRD(+)
      patients relapsed at 9, 15, 17 and 18 months after transplant, respectively. In
      contrast, only two patients of the nine MRD(-) patients have relapsed at 15 and
      38 months (P = 0.02), and four became MRD(+) at 6, 12, 30, and 42 months after
      transplantation, respectively. Of the 12 patients that were allografted, three
      (25%) died in the early post-transplant period, one had resistant disease, and
      eight (67%) achieved CR. Among the latter, no evidence of MRD post
      transplantation was observed in five cases, while a delayed clearance of MRD (up
      to 22 months after transplantation) was seen in two, and a persistent positivity
      of MRD after transplant was detectable in another patient until last follow-up
      (12 months). After a median follow-up of 43 months (range, 15-106), none of the
      responding patients had clinical or MRD relapse. These results show that in CLL
      the probability of achieving sustained MRD(-) CR is higher with allogeneic than
      with autologous transplants, and confirm the value of MRD assessment in the
      follow-up of patients transplanted for CLL.

PMID- 11237070
TI  - Analysis of the immunoglobulin heavy chain gene variable region of CD5-positive
      and -negative diffuse large B cell lymphoma.
AB  - We analyzed nucleotide sequence and intraclonal diversity of the rearranged
      immunoglobulin heavy chain gene variable region (VH gene) of CD5+ and CD5-
      diffuse large B cell lymphoma (DLBCL) to clarify the cell origin of de novo CD5+
      DLBCL. Ten cases of CD5+ DLBCL and 29 cases of CD5- DLBCL were analyzed. The
      frequencies of somatic mutation were 0.7 to 12.9% (average, 6.2%) in CD5+ DLBCL
      and 2.0 to 25.9% (average, 11.1%) in CD5- DLBCL. The ongoing mutation rate was
      estimated from the number of further single base-substitutions, expressed as a
      percentage of the total number of nucleotides in 10 cloned PCR products for each
      case (%). The averages of the ongoing mutation rate of CD5+ DLBCL (four cases)
      and CD5 DLBCL (seven cases) were 0.051% and 0.197%, respectively. The rate of
      CD5+ DLBCL was significantly lower than that of CD5- DLBCL (t-test, P = 0.024).
      These data may indicate that the cell origin of CD5+ DLBCL is different from that
      of CD5- DLBCL. CD5 is not an activated antigen in DLBCL, but a specific marker of
      the B1 subset of the B cells, and de novo CD5+ DLBCL may therefore be derived
      from this unique subset.

PMID- 11237071
TI  - Percentage of activated cytotoxic T-lymphocytes in anaplastic large cell lymphoma
      and Hodgkin's disease: an independent biological prognostic marker.
AB  - Recently, we demonstrated that the presence of high percentages of activated
      cytotoxic T-lymphocytes (CTLs) in biopsy specimens of both Hodgkin's disease (HD)
      and ALK negative anaplastic large cell lymphoma (ALCL) is associated with a poor
      prognosis. To test whether this biological prognostic factor is more important in
      predicting clinical outcome than histological diagnosis or clinical factors, we
      compared the prognostic value of these parameters in an expanded group of
      classical HD and ALK negative ALCL. Tumor biopsies of classical HD (n = 83) and
      ALK negative systemic nodal ALCL (n = 43) were investigated for the presence of
      activated CTLs by immunohistochemistry, using a monoclonal antibody directed
      against granzyme B. Percentages of activated CTLs were quantified using Q-PRODIT,
      and their prognostic value was compared to that of histological diagnosis and
      clinical parameters, including age and stage. Both in classical HD and ALK
      negative ALCL, a high percentage of activated CTLs (ie > or = 15%) identified a
      group of patients with poor overall and progression-free survival time, even when
      adjusted for stage. In multivariate analysis, percentage of activated CTLs
      remained a strong independent prognostic marker, and was more sensitive than
      histological diagnosis or clinical factors in predicting overall survival time.
      We conclude that a high percentage of activated CTLs in the reactive infiltrate
      of ALK negative ALCL and classical HD is a strong indicator for an unfavorable
      clinical outcome, regardless of histological diagnosis or clinical parameters. As
      such, this biological parameter may be an especially helpful tool to determine
      therapeutic strategies in cases in which the differentiation between ALK negative
      ALCL and HD remains difficult.

PMID- 11237072
TI  - Pros and cons of splenectomy in patients with myelofibrosis undergoing stem cell
      transplantation.
AB  - During fetal development, the spleen is a major hemopoietic organ. In the adult
      human, this task is relinquished to the bone marrow. However, under the stress of
      certain pathologic conditions, extramedullary hemopoiesis may again occur in the
      spleen. This is especially true for diseases of the marrow, in particular,
      myeloproliferative disorders such as agnogenic myeloid metaplasia, which is
      associated with severe fibrosis of the marrow space. At the same time, the spleen
      sequesters blood cells and contributes to peripheral blood cytopenias, which may
      improve following splenectomy. However, success is unpredictable, and the
      operative mortality of splenectomy is on the order of 10%. As a growing number of
      patients undergo hemopoietic stem cell transplantation as definitive therapy for
      myelofibrosis, the decision on splenectomy has additional ramifications since the
      spleen plays an important role in the kinetics of engraftment of donor cells and
      in immune reconstitution. We conclude from our analysis of available information
      that the benefit of splenectomy is difficult to predict, although after
      transplantation splenectomized patients have faster hemopoietic recovery. It
      appears that the most important indication for splenectomy in these patients is
      the relief of symptoms from massive spleen enlargement.

PMID- 11237073
TI  - Multicolor spectral karyotyping identifies novel translocations in childhood
      acute lymphoblastic leukemia.
AB  - We used a recently described molecular cytogenetic method, spectral karyotyping
      (SKY), to analyze metaphase chromosomes from 30 pediatric patients with acute
      lymphoblastic leukemia (ALL). This group included 20 patients whose leukemic
      blast cells lacked chromosomal abnormalities detected by conventional
      cytogenetics and 10 patients whose blast cells had multiple chromosomal
      abnormalities that could not be completely identified by G-banding analysis. In
      two of the 20 patients (10%) with apparently normal karyotypes, SKY identified
      three cryptic translocations: a t(7;8)(q34-35;q24.1) in one patient and a
      t(13;17)(q22;q21) and a der(19)t(17;19)(q22;p13) in another. Fluorescence in situ
      hybridization using subtelomeric probes proved the latter translocation to be a
      t(17;19). SKY analysis was also successful in defining the nature of the
      chromosomal abnormalities in four of the 10 patients with marker and derivative
      chromosomes. The identified abnormalities in the latter group included three
      novel translocations: a der(X)t(X;5)(p11.4;q31), a der(21)t(X;21)(p11.4;p11.2)
      and a t(X;9)(p11.4;p13). The presence of the t(X;9) was suggested by conventional
      cytogenetics. The application of fluorescence in situ hybridization using
      chromosome-specific painting probes and locus-specific probes complemented the
      SKY analysis by confirming the nature of the chromosome rearrangements defined by
      SKY and by identifying the amplification of the AML1/CBFA2 gene in one patient
      with a duplicated 21q. Our study demonstrates the utility of SKY in identifying
      novel translocations and in refining the identity of chromosomal abnormalities in
      leukemias.

PMID- 11237074
TI  - Frequent allelic loss of the BCL10 gene in lymphomas with the t(11;14)(q13;q32).

PMID- 11237075
TI  - Mutations of the transcription factor AML1/CBFA2 are uncommon in blastic
      transformation of chronic myeloid leukaemia.

PMID- 11237076
TI  - Mild cognitive impairment in the elderly.

PMID- 11237078
TI  - Update on treatment of influenza A and B with tamiflu.

PMID- 11237077
TI  - Complying with AAP Lyme disease recommendations.

PMID- 11237079
TI  - Sildenafil-simvastatin interaction: possible cause of rhabdomyolysis?

PMID- 11237080
TI  - 'Generally safe' NSAIDs?

PMID- 11237082
TI  - Disability prevention principles in the primary care office.
AB  - The simple request for a sick note can disguise important medical, psychologic or
      social issues. Disability may be influenced by social and cultural factors as
      well as by patient expectations. Assessment of impairment and subsequent
      disability is best made on the basis of objective data by use of a
      biopsychosocial model to ensure that the expression of disability does not mask
      other unaddressed psychologic or social issues. Enabling prolonged disability in
      such a situation can be a dysfunctional physician response to a maladaptive
      process. The physician's role is to treat the condition, to fulfill the
      appropriate role of patient advocate, to facilitate health (including resumption
      of activity), to offer proactive advice on the basis of prognosis, to be familiar
      with the patient's social obligations and resources and to provide education
      about the therapeutic benefits of returning to optimal function. This factual,
      medical-based approach offers an effective preventive strategy that will save
      many patients from unnecessary disability and morbidity.

PMID- 11237081
TI  - Treating onychomycosis.
AB  - Onychomycosis accounts for one third of fungal skin infections. Because only
      about one half of nail dystrophies are caused by fungus, the diagnosis should be
      confirmed by potassium hydroxide preparation, culture or histology before
      treatment is started. Newer, more effective antifungal agents have made treating
      onychomycosis easier. Terbinafine and itraconazole are the therapeutic agents of
      choice. Although the U.S. Food and Drug Administration has not labeled
      fluconazole for the treatment of onychomycosis, early efficacy data are
      promising. Continuous oral terbinafine therapy is most effective against
      dermatophytes, which are responsible for the majority of onychomycosis cases.
      Intermittent pulse dosing with itraconazole is as safe and effective as short
      term continuous therapy but more economical and convenient. With careful
      monitoring, patients treated with the newer antifungal agents have a good chance
      of achieving relief from onychomycosis and its complications.

PMID- 11237083
TI  - Evaluation of acute headaches in adults.
AB  - Classifying headaches as primary (migraine, tension-type or cluster) or secondary
      can facilitate evaluation and management A detailed headache history helps to
      distinguish among the primary headache disorders. "Red flags" for secondary
      disorders include sudden onset of headache, onset of headache after 50 years of
      age, increased frequency or severity of headache, new onset of headache with an
      underlying medical condition, headache with concomitant systemic illness, focal
      neurologic signs or symptoms, papilledema and headache subsequent to head trauma.
      A thorough neurologic examination should be performed, with abnormal findings
      warranting neuroimaging to rule out intracranial pathology. The preferred imaging
      modality to rule out hemorrhage is noncontrast computed tomographic (CT) scanning
      followed by lumbar puncture if the CT scan is normal. Magnetic resonance imaging
      (MRI) is more expensive than CT scanning and less widely available; however, MRI
      reveals more detail and is necessary for imaging the posterior fossa.
      Cerebrospinal fluid (CSF) analysis can help to confirm or rule out hemorrhage,
      infection, tumor and disorders related to CSF hypertension or hypotension.
      Referral is appropriate for patients with headaches that are difficult to
      diagnose, or that worsen or fail to respond to management

PMID- 11237084
TI  - Chronic vulvovaginal candidiasis.
AB  - Frequently ignored by the medical community, chronic vulvovaginal symptoms are
      relatively common and can frustrating for patients and physicians. Establishing a
      proper diagnosis will lay the foundation for an effective therapeutic therapeutic
      plan. Fungal cultures are an important component of the work-up. The most common
      causes of chronic vaginal symptoms are recurrent vulvovaginal candidiasis (RVVC),
      vulvar vestibulitis syndrome and irritant dermatitis. In patients with RVVC
      caused by Candida albicans, host factors may play an important role. Long-term
      oral antifungal therapy will break the pattern of recurrence in many patients.
      Infections caused by other species of yeast may be more resistant to standard
      treatment approaches.

PMID- 11237087
TI  - Earaches in children.

PMID- 11237085
TI  - Early diagnosis of dementia.
AB  - Until recently, the most significant issue facing a family physician regarding
      the diagnosis and treatment of dementia was ruling out delirium and potentially
      treatable etiologies. However, as more treatment options become available, it
      will become increasingly important to diagnose dementia early. Dementia may be
      suspected if memory deficits are exhibited during the medical history and
      physical examination. Information from the patient's family members, friends and
      caregivers may also point to signs of dementia. Distinguishing among age-related
      cognitive decline, mild cognitive impairment and Alzheimer's disease may be
      difficult and requires evaluation of cognitive and functional status. Careful
      medical evaluation to exclude treatable causes of cognitive impairment is
      important. Patients with early dementia may benefit from formal neuropsychologic
      testing to aid in medical and social decision-making. Follow-up by the patient's
      family physician is appropriate in most patients. However, a subspecialist may be
      helpful in the diagnosis and management of patients with dementia with an unusual
      presentation or following an atypical course.

PMID- 11237086
TI  - Bronchiolitis and your child.

PMID- 11237088
TI  - Vomiting and diarrhea in children.

PMID- 11237089
TI  - Coronary heart disease: reducing your risk.

PMID- 11237090
TI  - Heart failure.

PMID- 11237091
TI  - AAP issues recommendations on infection control in physicians' offices. American
      Academy of Pediatrics.

PMID- 11237092
TI  - Free radicals in the 1900's: from in vitro to in vivo.
AB  - Remarkable progress has been achieved in the past 100 years in the field of free
      radical chemistry, biology and medicine since the discovery of free radicals in
      1900. Free radical-mediated processes play a major role in the present industrial
      chemistry, but they also cause deleterious effects on rubber, plastics, oil
      products and foods. The importance of free radicals in vivo has been recognized
      increasingly from both positive and negative sides. Free radicals play an
      important role in phagocytosis, the production of some biologically essential
      compounds and possibly cell signaling. At the same time, they may cause oxidative
      modification of biological molecules, which leads to oxidative damage and
      eventually to various diseases, cancer and aging. The role and beneficial effects
      of antioxidants against such oxidative stress support this view. Furthermore,
      novel issues have been continuously found in this fascinating and yet
      controversial field of free radicals in biology. In this short article, the past
      work, present problems and future perspectives of free radicals in life science
      will be briefly discussed.

PMID- 11237093
TI  - Design of unsymmetrical azo initiators to increase radical generation efficiency
      in low-density lipoproteins.
AB  - Lipid peroxidation studies often employ the use of azo initiators to produce a
      slow, steady source of free radicals, but the lack of initiators capable of
      efficiently generating radicals in lipid regions has created persistent problems
      in these investigations. For example, experiments with symmetrical lipophilic or
      symmetical hydrophilic azo initiators increasingly suggest that their initiation
      mechanisms in low-density lipoproteins (LDL) rely upon the presence of alpha
      tocopherol to mediate peroxidation. We report here the synthesis and study of the
      new unsymmetrical azo compounds SA-1, SA-2, C-16, C-12, and C-8 that decompose
      over a range of convenient temperatures and improve radical generation efficiency
      and access to lipid compartments. The half-life for decomposition (tau(1/2)) of
      the unsymmetrical initiators at 37 degrees C in methanol covered a range of 121
      hours for SA-1, 77 hours for SA-2, and approximately 25 hours for the series C
      16, C-12, and C-8. Agarose gel electrophoresis of LDL incubated with these
      unsymmetrical initiators supports the conclusion that the initiators associate
      with lipoprotein without disrupting integrity of the particle. The unsymmetical
      initiator C-8 when compared to symmetical hydrophilic initiator C-0 is capable of
      providing increased peroxidation of LDL, as monitored by formation of cholesteryl
      linoleate oxidation products and consumption of alpha-tocopherol. Efficiency of
      radical generation in lipophilic and hydrophilic compartments was found to be
      represented with the use of the radical scavenger combination alpha-tocopherol
      and uric acid, but not with the use of N,N'-Diphenyl-p-phenylenediamine (DPPD)
      and uric acid. These unsymmetrical initiators, when compared to the widely used
      symmetrical azo initiators, provide an advantage of free radical production,
      lipophilic access, and constant radical generation in the investigation of lipid
      peroxidation in low-density lipoproteins.

PMID- 11237094
TI  - Hypochlorite-induced oxidation of thiols: formation of thiyl radicals and the
      role of sulfenyl chlorides as intermediates.
AB  - Activated phagocytic cells generate hypochlorite (HOCl) via release of hydrogen
      peroxide and the enzyme myeloperoxidase. HOCl plays an important role in
      bacterial cell killing, but excessive or misplaced production of HOCI is also
      known to cause tissue damage. Studies have shown that low-molecular-weight thiols
      such as reduced glutathione (GSH), and sulfur-containing amino acids in proteins,
      are major targets for HOCl. Radicals have not generally been implicated as
      intermediates in thiol oxidation by HOCl, though there is considerable literature
      evidence for the involvement of radicals in the metal ion-, thermal- or UV light
      catalysed decomposition of sulfenyl or sulfonyl chlorides which are postulated
      intermediates in thiol oxidation. In this study we show that thiyl radicals are
      generated on reaction of a number of low-molecular-weight thiols with HOCl. With
      sub-stoichiometric amounts of HOCl, relative to the thiol, thiyl radicals are the
      major species detected by EPR spin trapping. When the HOCl is present in excess
      over the thiol, additional radicals are detected with compounds which contain
      amine functions; these additional radicals are assigned to nitrogen-centered
      species. Evidence is presented for the involvement of sulfenyl chlorides (RSCl)
      in the formation of these radicals, and studies with an authentic sulfenyl
      chloride have demonstrated that this compound readily decomposes in thermal-,
      metal-ion- or light-catalysed reactions to give thiyl radicals. The formation of
      thiyl radicals on oxidation of thiols with HOCl appears to compete with non
      radical reactions. The circumstances under which radical formation may be
      important are discussed.

PMID- 11237095
TI  - Cellular response to bioactive lipid peroxidation products.
AB  - Reactive aldehydes, such as 4-hydroxy-2-nonenal, have been implicated as inducers
      in generating intracellular reactive oxygen species and activation of stress
      signaling pathways, that integrate with other signaling pathways to control
      cellular responses to the extracellular stimuli. Here, I briefly summarize a
      novel signaling pathway in cellular response, in which aldehyde-stimulated
      detoxification response is mediated by cyclooxygenase metabolites. These findings
      argue that lipid mediators could induce a cellular process that represents a
      cellular defense program against toxic compounds.

PMID- 11237096
TI  - Aldehyde reductase gene expression by lipid peroxidation end products, MDA and
      HNE.
AB  - Membrane lipid peroxidation results in the production of a variety of aldehydic
      compounds that play a significant role in aging, drug toxicity and the
      pathogenesis of a number of human diseases, such as atherosclerosis and cancer.
      Increased lipid peroxidation and reduced antioxidant status may also contribute
      to the development of diabetic complications. This study reports that lipid
      peroxidation end products such as malondialdehyde (MDA) and 4-hydroxynonenal
      (HNE) induce aldehyde reductase (ALR) gene expression. MDA and HNE induce an
      increase in intracellular peroxide levels; N-Acetyl-L-cysteine (NAC) suppressed
      MDA- and HNE-induced ALR gene expression. These results indicate that increased
      levels of intracellular peroxides by MDA and HNE might be involved in the
      upregulation of ALR.

PMID- 11237097
TI  - Analysis of the pathways of nitric oxide utilization in mitochondria.
AB  - The regulatory role that mitochondria play in cell dysfunction and cell-death
      pathways involves the concept of a complex and multisite regulation of cellular
      respiration and energy production signaled by cellular and intercellular
      messengers. Hence, the role of nitric oxide, as a physiological regulator acting
      directly on the mitochondrial respiratory chain acquires further relevance. This
      article provides a survey of the major regulatory roles of nitric oxide on
      mitochondrial functions as an expression of two major metabolic pathways for
      nitric oxide consumption: a reductive pathway, involving mitochondrial ubiquinol
      and yielding nitroxyl anion and an oxidative pathway involving superoxide anion
      and yielding peroxynitrite. The modulation of the decay pathways for nitrogen-
      and oxygen-centered radicals is further analyzed as a function of the redox
      transitions of mitochondrial ubiquinol. The interplay among these redox processes
      and its implications for mitochondrial function is discussed in terms of the
      mitochondrial steady-state levels (and gradients) of nitric oxide and superoxide
      anion.

PMID- 11237098
TI  - Cross-talk between NO and oxyradicals, a supersystem that regulates energy
      metabolism and survival of animals.
AB  - Mammalian tissues have large amounts of available ATP which are generated by
      oxidative phosphorylation in mitochondria. For the maintenance of the human body,
      a large amount of oxygen is required to regenerate these ATP molecules. A small
      fraction of the inspired oxygen is converted to superoxide radical and related
      metabolites even under physiological conditions. Most reactive oxygen species
      react rapidly with a variety of molecules thereby interfering with cellular
      functions and induce various diseases. Nitric oxide (NO) is an unstable gaseous
      radical with high affinity for various molecules, such as hemeproteins, thiols,
      and related radicals. NO easily penetrates through cell membrane/lipid bilayers,
      forms dissociable complexes with these molecules and modulates cellular
      metabolism and functions. Because NO has an extremely high affinity for the
      superoxide radical, the occurrence of the latter might decrease the biological
      function of NO. Thus, superoxide radicals in and around vascular endothelial
      cells play critical roles in the pathogenesis of hypertension and vasogenic
      tissue injury. Because NO also reacts with molecular oxygen, it rapidly loses its
      biological activity, particularly under ambient atmospheric conditions where the
      oxygen tension is unphysiologically high. Thus, biological functions of NO are
      determined by the local concentrations of molecular oxygen and superoxide
      radicals.

PMID- 11237099
TI  - Nitrotyrosine formation and its role in various pathological conditions.
AB  - The formation of peroxynitrite and nitrotyrosine was examined in a variety of in
      vitro and in vivo animal models and its relation to cell or tissue damage was
      examined. polymorphonuclear leukocyte (PMN)-induced injury to cardiac myocytes
      endothelial cells, activated PMN produced peroxynitrite. Peroxynitrite appears to
      be responsible for the injury but it was not a major mediator of endothelial cell
      injury. In the experiment of ischemia-reperfusion injury of the rat brain
      nitrotyrosine was formed in the peri-infarct and core-of infarct regions. The
      degradation curve of nitrotyrosine revealed that its t(1/2) was about 2.2 hours.
      In the radiation-induced lung injury of rats, nitrotyrosine was also formed but
      it was not the sole mechanism for the injury. Levels of nitrotyrosine correlated
      with the severity of myocardial dysfunction in the canine model of cytokine
      induced cardiac injury. Inhibition of NO generation abolished the formation of
      peroxynitrite and nitrotyrosine in all experiments. In conclusion; although
      nitrotyrosine is formed in a variety of pathological conditions where the
      generation of NO is increased, its presence does not always correlate with the
      severity of injury.

PMID- 11237100
TI  - The role of neutrophils and inflammation in gastric mucosal injury.
AB  - Gastric inflammation is a highly complex biochemical protective response to
      cellular/tissue injury. When this process occurs in an uncontrolled manner, the
      result is excessive cellular/tissue damage that results chronic inflammation and
      destruction of normal tissue. Current evidence suggests that Helicobacter pylori
      (H. pylori) infection and nonsteroidal anti-inflammatory drug (NSAID) ingestion
      are major causative factors in the pathogenesis of gastric mucosal injury in
      humans. In response to H. pylori infection or NSAID, neutrophils are recruited to
      the site of inflammation and generate reactive oxygen and nitrogen species and
      proteases. However, neutrophils are not able to kill the bacteria that live in
      the gastric mucus, and compounds produced by activated neutrophils themselves may
      be potentially harmful for normal tissue. It has been shown that leukocyte
      vascular endothelial cell interaction is regulated by various cell adhesion
      molecules, and that this interaction is directly or indirectly modified by many
      factors, the origin of which is H. pylori and NSAIDs. This review describes the
      potential role of neutrophils and neutrophil-associated inflammation for gastric
      oxidative stress and injury induced by H. pylori and/or NSAID.

PMID- 11237101
TI  - Fate of lipid hydroperoxides in blood plasma.
AB  - Cholesteryl ester hydroperoxide (CE-OOH) and phosphatidylcholine hydroperoxide
      (PC-OOH) are the major primary oxidation products of lipoproteins. CE-OOH is
      present in human and rat plasmas while PC-OOH is undetectable. This is likely due
      to the enzymatic (plasma glutathione peroxidase) and the nonenzymatic
      (apolipoproteins A and B-100) reducing activities of PC-OOH in plasma, and to the
      enzymatic conversion of PC-OOH to CE-OOH by lecithin:cholesterol acyltransferase
      in high density lipoproteins. The regioisomeric distribution of CE-O(O)H in human
      plasma indicates that free radical-mediated chain oxidation is an ongoing
      process, even in healthy young individuals.

PMID- 11237103
TI  - Diverse functions of antioxidants.
AB  - All biological organisms have developed a defense system against oxidative
      stress, which is comprised of many kinds of antioxidants. Antioxidants are
      classified by function into four categories; preventive antioxidants; radical
      scavenging antioxidants; repair and de novo antioxidants; and adaptation. Radical
      scavenging antioxidants have the greatest advantage. Although the activities of
      radical scavenging antioxidant are determined by several factors, their chemical
      structure is of key importance. Furthermore, radical scavenging antioxidants have
      been explored to have a novel function by which they regulate gene expression of
      cell.

PMID- 11237102
TI  - Carotenoid-containing unilamellar liposomes loaded with glutathione: a model to
      study hydrophobic-hydrophilic antioxidant interaction.
AB  - Unilamellar liposomes are used as a simple two-compartment model to study the
      interaction of antioxidants. The vesicle membrane can be loaded with lipophilic
      compounds such as carotenoids or tocopherols, and the aqueous core space with
      hydrophilic substances like glutathione (GSH) ascorbate, mimicking the interphase
      between an aqueous compartment of a cell and its surrounding membrane.
      Unilamellar liposomes were used to investigate the interaction of GSH with the
      carotenoids lutein, beta-carotene and lycopene in preventing lipid peroxidation.
      Lipid peroxidation was initiated with 2,2'-azobis-[2,4-dimethylvaleronitrile]
      (AMVN). Malondialdehyde (MDA) formation was measured as an indicator of
      oxidation; additionally, the loss of GSH was followed. In liposomes without added
      antioxidant, MDA levels of 119 +/- 6 nmol/mg phospholipid were detected after
      incubation with AMVN for 2 h at 37 degrees C. Considerably lower levels of 57 +/-
      8 nmol MDA/mg phospholipid were found when the liposomal vesicles had been loaded
      with GSH. Upon incorporation of beta-carotene, lycopene or lutein, the resistance
      of unilamellar liposomes towards lipid peroxidation was further modified. An
      optimal further protection was observed with 0.02 nmol beta-carotene/mg
      phospholipid or 0.06 nmol lycopene/mg phospholipid. At higher levels both these
      carotenoids exhibited prooxidant effects. Lutein inhibited lipid peroxidation in
      a dose-dependent manner between 0.02 and 2.6 nmol/mg phospholipid. With
      increasing levels of lycopene and lutein the consumption of encapsulated GSH
      decreased moderately, and high levels of beta-carotene led to a more pronounced
      loss of GSH. The data demonstrate that interactions between GSH and carotenoids
      may improve resistance of biological membranes towards lipid peroxidation.
      Different carotenoids exhibit specific properties, and the level for optimal
      protection varies between the carotenoids.

PMID- 11237104
TI  - The gastrointestinal tract: a major site of antioxidant action?
AB  - Diets rich in fruits and vegetables delay the onset of many age-related diseases,
      and contain a complex mixture of antioxidants (including ascorbate, carotenoids,
      vitamin E and other phenolics such as the flavonoids). However, diet also
      contains pro-oxidants, including iron, copper, H2O2, haem, lipid peroxides and
      aldehydes. Nitrite is frequently present in diet, leading to generation of
      reactive nitrogen species in the stomach. In considering the biological
      importance of dietary antioxidants, attention has usually focussed on those that
      are absorbed through the gastrointestinal tract into the rest of the body. In the
      present paper we develop the argument that the high levels of antioxidants
      present in certain foods (fruits, vegetables, grains) and beverages (e.g. green
      tea) play an important role in protecting the gastrointestinal tract itself from
      oxidative damage, and in delaying the development of stomach, colon and rectal
      cancer. Indeed, carotenoids and flavonoids do not seem to be as well absorbed as
      vitamins C and E. Hence their concentrations can be much higher in the lumen of
      the GI tract than are ever achieved in plasma or other body tissues, making an
      antioxidant action in the GI tract more likely. Additional protective mechanisms
      of these dietary constituents (e.g. effects on intercellular communication,
      apoptosis, cyclooxygenases and telomerase) may also be important.

PMID- 11237105
TI  - mRNA expression profile of a human cancer cell line in response to Ginkgo biloba
      extract: induction of antioxidant response and the Golgi system.
AB  - Supplementation of diets with plant extracts for health and prevention of
      degenerative diseases is popular. However the molecular basis of their
      therapeutic potentials are poorly defined. We hypothesized that in vitro assays
      that enable quantitative analysis of the gene expression profiles combined with
      targeted biochemical analysis can identify the potential effects of
      phytochemicals. The hypothesis was tested by application of GeneChips to define
      mRNA expressions of a human bladder cancer cell line incubated with a flavonoid
      containing extract of Ginkgo biloba leaves. The analysis of the transcriptional
      response revealed a net activation of transcription. Functional classification of
      the affected mRNAs showed the largest changes in the abundance of mRNAs for
      intracellular vesicular transport, mitochondria, transcription and antioxidants.
      The transcripts for hemeoxygenase-1, mitochondrial superoxide dismutase and the
      regulatory subunit of gamma-glutamyl-cysteinyl synthetase and their encoded
      proteins were elevated. The extract also increased intracellular glutathione, the
      transcripts for DNA repair and synthesis, and decreased 3H-thymidine
      incorporation. These results demonstrate that a flavonoid containing extract
      initiates an adaptive transcriptional response that augments the "antioxidant
      status" of the cells and inhibits DNA damage. These in vitro studies using
      GeneChips demonstrated a promising strategy for identifying nutritional
      supplement induced cellular responses that may have a role in counteracting
      chronic human diseases.

PMID- 11237107
TI  - Oxidative stress and aging in Caenorhabditis elegans.
AB  - Much attention has been focused on the hypothesis that oxidative damage plays in
      cellular and organismal aging. A mev-1 (kn1) mutant of Caenorhabditis elegans,
      isolated on the basis of its methyl viologen (paraquat) hypersensitivity, is also
      hypersensitive to elevated oxygen levels. Unlike the wild type, its life span
      decreases dramatically as oxygen concentrations are increased from 1% to 60%.
      Strains, which bear this mutation, accumulate fluorescent materials and protein
      carbonyl groups, markers of aging, at faster rates than the wild type. We have
      cloned mev-1 gene by transformation rescue and found that it is, in fact, the
      previously sequenced gene (cyt-1) that encodes succinate dehydrogenase cytochrome
      b. A missense mutation abolishes complex II activity in the mitochondrial
      membrane but not succinate dehydrogenase enzyme activity per se. These data
      suggest that CYT-1 directly participates in electron transport from FADH2 to
      coenzyme Q. Moreover, mutational inactivation of this process renders animals
      susceptible to oxidative stress and, as a result, leads to premature aging.

PMID- 11237106
TI  - Redox regulation by thioredoxin superfamily; protection against oxidative stress
      and aging.
AB  - Thioredoxin (TRX) is a 12 kD protein with redox-active dithiol in the active
      site; -Cys-Gly-Pro-Cys-. We originally cloned human TRX as adult T cell leukemia
      derived factor (ADF) produced by HTLV-I transformed cells. TRX and related
      molecules maintain a cellular reducing enviroment, working in concert with the
      glutathione system. Physiologically, TRX has cytoprotective effects against
      oxidative stress. TRX promotes DNA binding of transcription factors such as NF
      kB, AP-1, p53, and PEBP-2. The TRX superfamily, including thioredoxin-2
      (mitochondrial thioredoxin) and glutaredoxin, are involved in biologically
      important phenomena via the redox-regulating system. Thioredoxin-binding protein
      2, which we recently identified by a yeast two-hybrid system, is a type of
      endogenous modulator of TRX activity. TRX is secreted from the cells and exhibits
      cytokine-like and chemokine-like activities. Redox regulation by TRX plays a
      crucial role in biological responses against oxidative stress.

PMID- 11237108
TI  - A comparison of recent trends in infant mortality among twins and singletons.
AB  - Overall infant mortality rates have steadily declined in recent years. The goal
      of this study was to examine whether recent declines in infant mortality were
      similar for twins and singletons, and to assess the impact of differing
      birthweight distributions on these relationships. Linked birth and infant death
      records for 1985-86 and 1995-96 were used to calculate infant mortality rates for
      twins and singletons for the two time periods. Bootstrap simulations were used to
      estimate rates of decrease between the two time periods and to determine whether
      these rates differed between twins and singletons. Between 1985-86 and 1995-96,
      infant mortality among twins declined significantly faster than among singletons
      (36% vs. 29%, P < 0.05). This difference was true for both black and white
      infants (black: 28% for twins vs. 22% for singletons; white: 38% for twins vs.
      31% for singletons). Within birthweight categories, infant mortality declined
      more rapidly among twins than among singletons, although differences were not
      always significant. Factors and circumstances that contributed to the infant
      mortality decline in the United States have benefited twins to a greater extent
      than singletons.

PMID- 11237109
TI  - Effect of maternal age, smoking and deprivation on birthweight.
AB  - Low birthweight is often used as a health indicator. This paper reports the
      findings of a cohort study, which were analysed to determine the relationship, if
      any, between the age of the mother and birthweight given the mother's smoking
      habits and the level of social deprivation of the mother's place of residence.
      The data used were extracted from those data routinely collected by the
      Information and Statistics Division of the National Health Service, Scotland.
      Information on 178,801 singleton live births occurring between 1992 and 1994 was
      used in the analysis. The factors considered were those available directly from
      the official records. The level of social deprivation was measured using
      Carstairs index based on the postcode sector. Although younger and older mothers
      have lighter babies, on average, it was found that this effect can be largely
      explained by differences in the smoking habits and level of deprivation of the
      mothers. Birthweight, adjusted for gestational age, sex of the baby and parity of
      the mother, was significantly lower for babies born to mothers who smoked during
      pregnancy. It is clear, however, that the detrimental effect of smoking increases
      with the age of the mother. Although adjusted birthweight was lower for those in
      areas of high deprivation, this effect is small compared with the effect of
      smoking. Any attempt to decrease the percentage of low-birthweight babies must
      focus on reducing the percentage of mothers who smoke.

PMID- 11237110
TI  - Making factual knowledge public.

PMID- 11237111
TI  - Cumulative impact of early maternal marital age during the childbearing period.
AB  - Early marriage of girls, close to age of menarche, is a widespread practice in
      Arab countries. Knowledge on the cumulative effect of early maternal marriage on
      maternal and infant health during the childbearing period is insufficient. The
      objectives of this study were to estimate the prevalence of early maternal
      marriage in Jeddah, identify its relation with other maternal risk factors, and
      investigate the cumulative impact of early maternal marriage on subsequent
      maternal health and pregnancy outcomes throughout the reproductive period. Data
      were collected from six randomly selected primary health care units in Jeddah
      City. Married women with an infant < or = 12 completed months of age were
      interviewed and information on sociodemographic characteristics, maternal health
      and previous pregnancy outcomes were collected. Early marriage of girls before
      the age of 16 years accounted for 26.5% of the study population and was reported
      by a third of mothers currently below the age of 20 years. Illiterate mothers,
      housewives, multiparae, smokers and those married to a relative reported the
      highest proportion of marriages before their sixteenth birthday. Those who
      married before the age of 16 were at about double the risk of developing chronic
      diseases and experiencing miscarriage, stillbirths and infant deaths. These
      results suggest that early maternal marriage still exists in our community and is
      intimately related to other maternal risk factors. Maternal marriage < 16 years
      appears to be fraught with insecurities for the mother and infant throughout the
      whole length of the childbearing period and not merely the first pregnancy. Thus,
      even if culture norms claim early marriage of girls, it should be discouraged
      before the age of 16 years. Moreover, it is recommended that future research on
      maternal and infant health considers the cumulative effect of the various risk
      factors during the whole reproductive period and not only a single pregnancy
      outcome.

PMID- 11237112
TI  - The effect of vaginal bleeding during pregnancy on preterm and small-for
      gestational-age births: US National Maternal and Infant Health Survey, 1988.
AB  - We examined the effects of vaginal bleeding during pregnancy on preterm and small
      for-gestational-age (SGA) births using data from the 1988 US National Maternal
      and Infant Health Survey. We examined the severity of vaginal bleeding and
      separated the preterm births into subsets by the degree of prematurity (< 32, 32
      33, 34-36 weeks' gestation). We also evaluated associations stratified by race.
      Multiple logistic regression analysis showed that vaginal bleeding was associated
      with an increased risk of preterm birth, with a more pronounced elevated risk for
      preterm birth before 34 weeks' gestation and a notably stronger association for
      more severe bleeding that occurred in both the first and the second half of
      pregnancy. Odds ratios, but not risk differences, for birth before 34 weeks'
      gestation were greater for white women with vaginal bleeding than for black
      women. There was no association between vaginal bleeding during pregnancy and SGA
      births.

PMID- 11237113
TI  - The epidemiological transition in maternal and child health in a Brazilian city,
      1982-93: a comparison of two population-based cohorts.
AB  - Two studies carried out in 1982 and 1993 in the city of Pelotas, Southern Brazil,
      provide a unique opportunity for assessing the impact on maternal and child
      health of the economic and health care changes, which took place in Brazil in
      this period. The cohorts of mothers and infants of 1982 and 1993 were studied
      from the time of delivery. In both years, all mothers identified in the city's
      maternity hospitals answered a standardised questionnaire and their infants were
      examined. Over 99% of all children born in the city in each of the 2 years were
      included in the cohorts. Deaths occurring among these children were monitored
      prospectively, as well as all hospital admissions in the 1993 cohort. In the 1982
      study, attempts were made to locate a 25% sample of the children at the mean age
      of 12 months using the addresses collected at the hospital (82% of the children
      were located), and all of the cohort children at the mean age of 20 months and 42
      months, through a city census (87% were located in both follow-ups). In the 1993
      study, 20% of all children plus all low birthweight infants were sought at 12
      months of age, using the addresses collected at the hospital, and 95% were
      successfully traced. There was a 12% fall in the number of births occurring in
      1993 (5,304 births), in comparison with 1982 (6,011 births), in spite of the
      increase in the population of reproductive age in the city during the decade.
      There was a marked difference in maternal height and weight at the beginning of
      pregnancy, with women giving birth in 1993 being, on average, 3.4 cm taller and
      2.5 kg heavier than those who gave birth in 1982. The proportion of preterm
      babies (<37 weeks), measured by the date of last menstrual period, increased from
      5.6% in 1982 to 7.5% in 1993. The median duration of breast feeding increased
      from 3.1 months in 1982 to 4.0 months in 1993. At 12 months of age, the
      prevalence of deficit of weight for age decreased from 5.4% in 1982 to 3.7% in
      1993. The prevalence of deficit of height for age, however, increased from 5.3%
      to 6.1%. The perinatal mortality rate dropped 31%, from 32.2 per 1,000 births in
      1982 to 22.1 deaths per 1,000 births in 1993. There was also a marked reduction
      in the infant mortality rate, from 36.4 per 1,000 livebirths in 1982 to 21.1 per
      1,000 livebirths in 1993. The findings of the study indicate that there were
      improvements in the decade for most of the indicators evaluated, with the
      exception of birthweight and gestational age. It appears that improvements in
      perinatal and infant mortality rates are largely due to improvements in the
      health care sector.

PMID- 11237114
TI  - Risk factors for pre-eclampsia/eclampsia among working women in Mexico City.
AB  - This study examined risk factors for pre-eclampsia/eclampsia in a population
      based sample of pregnant working women in Mexico City. Over a 3-month period, all
      women who gave birth at three major hospitals and who had worked for at least 3
      months during pregnancy were interviewed. After excluding mothers with multiple
      gestations or infants with birth defects, and previous diagnoses of hypertension,
      chronic renal disease or diabetes, 131 of 2,436 women (5.4%) had been diagnosed
      with pre-eclampsia and/or eclampsia. The frequency was much higher among women of
      low socio-economic status: 12% of uninsured women (SSA) compared with 4.2% of
      private sector employees (IMSS) and 1.3% of public sector employees (ISSSTE).
      After adjusting for education, women working in services (OR = 1.68, 95% CI =
      1.01, 2.81) and in retail (OR = 1.99, 95% CI = 1.18, 3.37), primiparae (OR =
      2.64, 95% CI = 1.65, 4.21) and women whose pregestational weight was > or = 55 kg
      (OR = 2.02, 95% CI = 1.34, 3.04) were at increased risk. Efforts to develop and
      evaluate intervention programmes should target hospitals serving the uninsured
      (SSA) if reduction in the number of preventable maternal deaths in Mexico is to
      be achieved. Such programmes should also target service and retail workers and
      identify women with poor glycaemic control early in pregnancy.

PMID- 11237115
TI  - Perinatal factors and risk of neuroblastoma.
AB  - Neuroblastoma is a malignancy commonly diagnosed during infancy or early
      childhood, raising speculation about the role of perinatal factors and risk of
      disease. Using a case-control design, cases included 155 infants and children
      aged 0-5 years with histologically confirmed neuroblastoma diagnosed and reported
      to the New York State Cancer Registry between 1976 and 1987. Controls were
      randomly selected from the State's Livebirth Registry and were frequency matched
      to cases on year of birth (n = 310). Medical records of cases were used to verify
      histology and stage of disease. Data on perinatal factors were ascertained from
      birth certificates and standardised telephone interviews with mothers.
      Unconditional logistic regression was used to estimate (un)adjusted odds ratios
      (OR) and 95% confidence intervals (CI). Both preterm (< 37 weeks) and post-term
      (> 42 weeks) birth were associated with a reduction in risk (OR = 0.4 [CI = 0.1,
      0.9] and OR = 0.3 [CI = 0.1, 0.7] respectively) after controlling for confounders
      in unconditional logistic regression analysis. Elevated risk factors included:
      smoking during pregnancy (OR = 1.6; CI = 0.9, 2.8), contracted pelvis (OR = 2.3;
      CI = 0.6, 9.8), birth injury (OR = 2.9; CI = 0.3, 24.9) and 1-min Apgar Score <
      or =3 (OR = 6.0; CI = 0.9, 38.6); all confidence intervals included one. These
      data suggest that extremes in gestation may be associated with a reduced risk,
      although aetiological mechanisms remain unknown.

PMID- 11237116
TI  - Fetal and neonatal death from maternally acquired infection.
AB  - Infection is a potentially preventable cause of perinatal mortality but there is
      only limited epidemiological information on which to develop prophylactic
      guidelines. The aim of this study was to determine the population incidence of
      perinatal death from maternally acquired infection and to describe the
      responsible organisms and antibiotic sensitivities, and also the associated risk
      factors. Fetal and neonatal deaths from perinatal infection in the former
      Northern Health Region, United Kingdom, were identified for the years 1981-96
      using data held by the Perinatal Mortality Survey, and the obstetric, paediatric
      and pathology case notes were reviewed. Maternally acquired bacterial infection
      of the baby was identified as responsible for 60 pre-delivery deaths and 142 post
      delivery deaths among babies of 24 or more weeks gestation at birth between 1981
      and 1996. There were 630,206 livebirths and 3,591 registered stillbirths in the
      survey area during this time. Bacterial infection was also considered the primary
      cause of death in 64 fetuses where delivery occurred at 20-23 weeks gestation
      between 1989 and 1996. Although group B streptococcus was the commonest single
      organism it was only responsible for 30% of all infectious deaths from 24 weeks
      gestation onwards. Ampicillin resistance was more common in the second half of
      the study. Infection remains an important cause of perinatal mortality but
      responsible organisms and antibiotic sensitivities have changed significantly
      over time. Although 80% of the post-delivery deaths would have received
      intrapartum antibiotics if current guidelines had been in place, the choice of
      antibiotics and identification of risk groups requires careful consideration.

PMID- 11237117
TI  - A prospective study of antibiotic use and associated infections in young
      children.
AB  - This study examines antibiotic usage and associated infections in infants and
      young children in Iowa. Longitudinal data were collected using a cohort recruited
      at birth from eight hospitals in eastern Iowa. Parents of recruited children were
      mailed questionnaires at 6 weeks, and 3, 6, 9, 12, 16, and 20 months of age. The
      cumulative incidence of antibiotic use and associated infections was determined
      using Kaplan-Meier survival analysis. There were data on 1,368 children.
      Antibiotic use was common in our cohort and increased with age. Beginning at age
      3 months, approximately 50% of the cohort was exposed to an antibiotic during
      each reporting period. Otitis media was the most common indication and was
      responsible for 67.3% of antibiotic use. Children were most frequently treated
      with amoxicillin, followed by the cephalosporins and sulphonamides. By 12 and 20
      months of age 79.0% and 92.5% of the children, respectively, had been treated
      with at least one course of antibiotics. Children received antibiotics for a
      median of 43 days by 20 months of age. Males were more likely to experience any
      antibiotic exposure than females (hazard ratio = 1.18) and showed a trend for
      more days of use (P = 0.052). There was a small but significant variation in
      antibiotic usage in the different recruitment communities (P = 0.02).

PMID- 11237118
TI  - Safety of the Canadian blood supply in 1980-85: using a paediatric cohort for
      risk assessment of human immunodeficiency virus (HIV) infection.
AB  - The risk of HIV from transfusions in Canada in the period 1980-85 was estimated,
      using the information from a transfused paediatric cohort. Children who were
      transfused between January 1980 and November 1985 at a tertiary care paediatric
      hospital were contacted by letter. With this notification, HIV testing for
      recipients was recommended. HIV testing histories were obtained. The number
      tested for HIV was estimated from the questionnaire responses and from data
      matching with the HIV-testing laboratory. Cases of HIV infection were identified
      through multiple sources. In this cohort, 11,028 children were transfused a mean
      of 21 units. Of the 10,220 living recipients, the estimated proportion tested for
      HIV was 86% to 91%. Thirty-one cases of HIV infection were identified,
      representing 0.28% of the cohort but 0.34% of those expected to have been tested.
      The estimated HIV incidence per 1,000 units transfused ranged from 0.028 [95% CI
      0.0007, 0.155] in 1980 to 0.445 [95% CI 0.2592, 0.712] in 1985. This suggests
      that the risk of HIV from transfusions in Canada continued to rise until the
      implementation of HIV testing of donors in November 1985.

PMID- 11237119
TI  - ALSPAC--the Avon Longitudinal Study of Parents and Children. I. Study
      methodology.
AB  - ALSPAC (The Avon Longitudinal Study of Parents and Children, formerly the Avon
      Longitudinal Study of Pregnancy and Childhood) was specifically designed to
      determine ways in which the individual's genotype combines with environmental
      pressures to influence health and development. To date, there are comprehensive
      data on approximately 10,000 children and their parents, from early pregnancy
      until the children are aged between 8 and 9. The study aims to continue to
      collect detailed data on the children as they go through puberty noting, in
      particular, changes in anthropometry, attitudes and behaviour, fitness and other
      cardiovascular risk factors, bone mineralisation, allergic symptoms and mental
      health. The study started early during pregnancy and collected very detailed data
      from the mother and her partner before the child was born. This not only provided
      accurate data on concurrent features, especially medication, symptoms, diet and
      lifestyle, attitudes and behaviour, social and environmental features, but was
      unbiased by parental knowledge of any problems that the child might develop. From
      the time of the child's birth many different aspects of the child's environment
      have been monitored and a wide range of phenotypic data collected. By virtue of
      being based in one geographic area, linkage to medical and educational records is
      relatively simple, and hands-on assessments of children and parents using local
      facilities has the advantage of high quality control. The comprehensiveness of
      the ALSPAC approach with a total population sample unselected by disease status,
      and the availability of parental genotypes, provides an adequate sample for
      statistical analysis and for avoiding spurious results. The study has an open
      policy in regard to collaboration within strict confidentiality rules.

PMID- 11237120
TI  - Performance of a new pubertal self-assessment questionnaire: a preliminary study.
AB  - We describe the performance of a new, self-assessment questionnaire that aims to
      measure pubertal status by using gender-specific line drawings of the Tanner
      puberty stages. The study was carried out on 103 children aged 12-16 years
      attending a paediatric endocrinology outpatient clinic and used physical
      examination by clinic doctors as the 'gold standard'. Of 133 consecutive,
      eligible children, 108 (81%) agreed to participate in the study. Data were
      collected from 62 (60%) males and 41 (40%) females. Mean age was 14.78 years (SD
      = 1.26 years, range 12.08-16.98 years). For the pubic hair distribution Tanner
      stage, there was agreement to within one Tanner stage for 90 children (88%),
      weighted kappa statistic for inter-rater agreement = 0.68 [95% CI 0.49,0.87]. For
      the female breast/male genitalia Tanner stage, there was agreement to within one
      Tanner stage for 75 children (76%), kappa = 0.48 [95% CI 0.31,0.64]. The children
      tended to underestimate their stage of pubertal development. Overall, the kappa
      statistics implied good agreement for the pubic hair question and moderate
      agreement for the breast/genitalia stage question in both girls and boys. The
      questionnaire may prove useful in situations such as large-scale epidemiological
      studies, in which direct examination of children to determine pubertal status is
      not possible, and further validation in normal adolescents is warranted.

PMID- 11237121
TI  - No constitutive defect in phagocytosis of apoptotic cells by resident peritoneal
      macrophages from pre-morbid lupus mice.
AB  - Antibodies against nucleosomes are a hallmark of systemic lupus erythematosus
      (SLE). Nucleosomes are uniquely formed during apoptosis, through cleavage of
      chromatin by nucleases. Increased exposure of nucleosomes to the immune system
      could play a role in the induction of the autoimmune repertoire in SLE. To
      determine whether there exists a constitutive defect in the clearance of
      apoptotic cells, resident peritoneal macrophages from pre-morbid SLE-prone MRL
      and New Zealand (NZ) mice were analysed for their efficacy to phagocytose
      apoptotic cells in vitro. Although differences in phagocytic efficacy of up to
      50% between different strains of mice were found, these were not related to SLE
      development. To evaluate whether macrophages from SLE-prone mice are more
      susceptible to phagocytic 'exhaustion', resident peritoneal macrophages were
      challenged by 20 h of additional culture in the presence of apoptotic cells. In
      both lupus and control strains this led to an increased capacity to phagocytose
      fresh apoptotic cells (increase between 15 and 92%). As a control, macrophages
      from all strains were also exposed to 20 h of additional culture without
      apoptotic cells. Under this condition resident peritoneal macrophages from all
      SLE-prone strains, and of the SLE-parental strain NZB, displayed a significant
      decrease in their efficacy to phagocytose apoptotic cells (decrease between 16
      and 55%). Together, these findings do not support the hypothesis that a
      constitutive defect in the clearance of apoptotic cells, as evaluated by testing
      resident peritoneal macrophages, plays an important role in the induction of SLE.

PMID- 11237122
TI  - Immunologic and hematologic properties of antibodies to prothrombin and
      plasminogen in a mouse model.
AB  - Antibodies to prothrombin have been associated with venous and arterial
      thrombosis, and they cross-react with a structurally closely related protein
      plasminogen. We immunised 16 mice with human prothrombin and 15 mice with human
      plasminogen. Mice immunised with prothrombin developed cross-reactive antibodies
      to plasminogen (12/16), beta2-glycoprotein I (4/16), tissue-type plasminogen
      activator (6/16) and cardiolipin (11/16). Mice immunised with plasminogen
      developed cross-reactive antibodies to prothrombin (8/15), tissue-type
      plasminogen activator (2/12) and cardiolipin (5/12). Functional effects of
      antibodies were examined. Immunisation with prothrombin induced lupus
      anticoagulant activity in 9/14 mice. In mice immunised with plasminogen, radial
      fibrinolysis was inhibited in 8/10 and plasminogen activation in the chromogenic
      assay was inhibited in 9/11. No cross-functionality was observed. In conclusion,
      antibodies to prothrombin and plasminogen cross-react in vivo. Antibodies to
      prothrombin and plasminogen have different functional profiles, immunisation with
      prothrombin leads to prolonged blood clotting time, and immunisation with
      plasminogen induces antibodies interfering with fibrinolysis.

PMID- 11237123
TI  - In vitro-activated human lupus T cells express normal estrogen receptor proteins
      which bind to the estrogen response element.
AB  - We have shown that estrogen receptor (ERalpha, ERbeta) transcripts are expressed
      in SLE and normal T cells. In this study, T cell nuclear extracts from female
      lupus patients and normal donors were tested for biologically active ER proteins
      capable of binding to the human estrogen response element (hERE) by
      electrophoretic mobility shift assays. When peripheral blood T cells were
      stimulated with 17beta-estradiol (E2), PMA and ionomycin, two major retarded
      bands in T cell nuclear extracts exhibited a migration pattern similar to slow
      migrating protein-ERE complexes in human breast cancer cell extracts. T cells
      cultured only with E2 did not have these complexes. The formation of the
      complexes was inhibited by competition with the hERE cold oligonucleotide and
      partially with anti-ERalpha antibodies. There was no notable difference in the
      migration pattern of ERE-binding proteins between the SLE and normal T cell
      extracts. Together, these results suggest that activated human T cells, whether
      lupus-derived or normal-derived, contain biologically active ERalpha proteins.
      Other factors may be responsible for differential sensitivity of lupus T cells to
      estrogen.

PMID- 11237124
TI  - Myocardial microangiopathy associated with antiphospholipid antibodies.
AB  - Myocardial thrombotic microangiopathy is a well described post-mortem finding in
      patients with the catastrophic antiphospholipid (APL) syndrome. However, it has
      been only very rarely imaged in living patients. Here, we report two patients
      with APL antibodies presenting with scintigraphic, electrocardiographic and/or
      echocardiographic evidence of (sub)acute myocardial ischaemia, despite a normal
      coronary angiography. Formal proof of a thrombotic microangiopathy was obtained
      by a kidney biopsy in one patient. We emphasize the value of 99mTc-MIBI (2
      methoxy isobutyl isonitrile) exercise stress myocardial scintigraphy for the
      detection of cardiac microangiopathy associated with the APL syndrome.

PMID- 11237126
TI  - A case of systemic lupus erythematosus complicated with multicentric
      reticulohistiocytosis (MRH): successful treatment of MRH and lupus nephritis with
      cyclosporin A.
AB  - We document the first case of a patient who manifested systemic lupus
      erythematosus (SLE) complicated with multicentric reticulohistiocytosis (MRH).
      Neither intravenous steroid nor cyclophosphamide (CY) pulse therapies were fully
      effective against multiple MRH-related tumors that appeared on the left ankle
      joint and interphalangeal joints of both hands. In contrast, treatment with
      cyclosporin A (CyA) resulted in a marked regression of these nodules within one
      month, together with a complete remission of both MRH and lupus nephritis. We
      propose CyA as an alternative choice for the treatment of MRH.

PMID- 11237125
TI  - Therapeutic response and long-term follow-up in a systemic lupus erythematosus
      patient presenting with Kikuchi's disease.
AB  - Kikuchi's disease (KD) can occur in association with systemic lupus erythematosus
      (SLE). The treatment of concomitant diseases, however, is unclear. We describe a
      case of a 45-y-old man who presented with generalized histiocytic necrotizing
      lymphadenitis, fever, malaise and weight loss. Ten months later he also developed
      arthritis, serositis, anemia, leukopenia and lymphopenia. ANA, anti-Smith, anti
      snRNP and anti-Ro antibodies were positive. He responded rapidly and favorably to
      mid-dose prednisone. Hydroxychloroquine, added 5 months later, allowed tapering
      down and discontinuation of prednisone treatment. He has remained in complete
      remission for 5 years.

PMID- 11237127
TI  - Living with lupus--a physician's perspective.

PMID- 11237128
TI  - Placentation, antiphospholipid syndrome and pregnancy outcome.
AB  - The antiphospholipid antibodies (aPLs) are a diverse group of autoantibodies
      associated with a pattern of disease known as antiphospholipid syndrome (APS).
      Pregnancy complications secondary to placental insufficiency are key features of
      this disease. The mechanisms underlying the placental pathology remain unclear.
      In this article the process of placentation in healthy and pathological
      pregnancies is reviewed. The evidence for defective placentation in APS
      pregnancies and involvement of aPLs in this process is summarized. Finally
      hypotheses based on the interpretation of these studies are discussed.

PMID- 11237129
TI  - Prevalence and isotype distribution of antiphospholipid antibodies in Chilean
      patients with systemic lupus erythematosus (SLE).
AB  - Previous studies have demonstrated that ethnicity plays a role in the prevalence,
      isotype distribution, and clinical significance of anticardiolipin (aCL) and anti
      beta2 glycoprotein I (abeta2-GPI) antibodies in systemic lupus erythematosus
      (SLE) patients. Few studies have been done in Latin American populations. Serum
      samples from 129 Chilean SLE patients were tested for IgG, IgM and IgA aCL and
      abeta2-GPI by ELISA. Clinical data were reviewed with the focus on clinical
      manifestations of antiphospholipid syndrome (APS). Positivity for at least one
      isotype of aCL was found in 30% of patients, while only 10% were positive for at
      least one isotype of abeta2-GPI. IgG was the most prevalent isotype for aCL
      (16%), and the isotype distribution was similar (4%) for abeta2-GPI. In general,
      the presence of aCL was significantly associated with the presence of abeta2-GPI,
      but a number of samples were positive for only one antibody, some of them
      associated with clinical manifestations of APS. ACL antibodies at medium-high
      titers were significantly correlated with thrombosis (P = 0.0007) and fetal loss
      (P = 0.009); however, the sensitivity of abeta2-GPI for detecting thrombosis and
      fetal loss was lower than aCL (19 and 17% vs 56 and 50%, respectively), and the
      specificity slightly higher (91 and 90% vs 84 and 82%). In Chilean SLE patients,
      aCL and abeta2-GPI antibodies are important in the evaluation of patients with
      APS. However, the utility of abeta2-GPI antibodies was limited by the low
      prevalence of these antibodies in comparison with other ethnic groups. Further
      studies are needed to define the basis of the observed differences among ethnic
      groups.

PMID- 11237131
TI  - Non-thyphoidal salmonellosis in patients with systemic lupus erythematosus. A
      study of fifty patients and a review of the literature.
AB  - The objective of this study was to characterize the clinical profile of lupus
      patients with non-typhoidal salmonellosis. A retrospective review of the clinical
      charts of lupus patients diagnosed with bacteriologically proven non-typhoidal
      salmonellosis over the last 20 y was undertaken, paying special attention to risk
      factors, clinical presentation and treatment outcome. Most episodes were
      bacteraemic without a localizing focus; and some patients were afebrile. They
      usually occurred in patients prone to opportunistic infections, and at times of
      increased immunosuppression given for lupus flares (especially nephritis).
      However, salmonellosis also occurred in some patients presenting with lupus. The
      C-reactive protein level was found to be significantly higher during the
      infective episodes compared to episodes of non-infective febrile lupus flare. All
      isolates were sensitive to the usual first-line antibiotics and eminently
      treatable with 3 weeks of appropriate antibiotics without recurrence/persistence
      or significant morbidity/mortality, the exceptions being spinal osteomyelitis and
      septic arthritis involving deformed joints requiring surgical debridement and
      prolonged antibiotic therapy for eradication. Mortality occurred in the setting
      of septic shock from mixed-microbial sepsis and major organ failure from active
      lupus. There is a high association of non-epidemic, non-typhoidal salmonellosis
      with SLE, especially in patients with active disease on intensified
      immunosuppression. The C-reactive protein value may be helpful in distinguishing
      between fever from a pure lupus flare and one complicated by infection.

PMID- 11237130
TI  - Anti-insulin antibodies and the natural autoimmune response in systemic lupus
      erythematosus.
AB  - Systemic lupus erythematosus (SLE) is characterized by the finding of ample serum
      autoantibodies. The role and the origin of many of these antibodies are still
      obscure. The aim of this work was to study the occurrence of anti-insulin
      antibodies (AIA) in SLE, and to postulate, based on AIA determination, on the
      mechanisms involved in the production of some autoantibodies in SLE. IgG and lgM
      AIA, anti-DNA antibodies (ADA) and anti-tetanus toxoid antibodies (ATA) were
      determined using ELISA in sera and B-lymphocytes culture media of 24 SLE
      patients, 10 healthy controls and 19 insulin-dependent diabetes mellitus (IDDM)
      patients. B- and T-lymphocytes were isolated using Ficoll gradient, depleted of T
      cells using cyclosporin A, EBV infected and grown in medium. The frequencies of
      IgM-AIA and IgG-ADA were higher in SLE patients than in healthy controls (P <
      0.02 and P < 0.05, respectively). The rate of IgM-AIA in SLE and IDDM was
      comparable, while IgG-AIA was significantly less common in SLE than in IDDM (P <
      0.05). The prevalence of ATA in SLE patients and healthy controls was similar.
      These findings increase the spectrum of the humoral autoimmune response in SLE
      and suggest that part of it (natural autoantibodies) is independent of antigen
      driven response.

PMID- 11237132
TI  - Early damage as measured by the SLICC/ACR damage index is a predictor of
      mortality in systemic lupus erythematosus.
AB  - The aim of this study was to determine whether early damage accrued in SLE as
      measured by the SLICC/ACR Damage Index predicts mortality in an inception cohort
      of lupus patients that have been followed prospectively in a single centre. SLE
      patients from the University of Toronto Lupus Clinic presenting within 1 y of
      their diagnosis prior to 1988 were included. This enabled all patients to be
      potentially followed for at least 10 y. Yearly SLICC/ACR Damage Index scores were
      determined for each patient. Early damage was defined as a score > or = 1 and no
      damage as a score of 0 at the initial assessment. Log rank test was used to
      compare the survival experience between those with and without damage, with all
      patients being censored at 10 y. Two-hundred and sixty-three patients were
      identified in this inception cohort who were followed for 10 y. One-hundred and
      ninety patients (72%) had a SLICC/ACR Damage Index score of 0 (no damage) while
      73 patients (28%) had at least one SLICC/ACR Damage Index item scored (early
      damage). Twenty-five percent of lupus patients who exhibited damage at their
      first SLICC/ACR Damage Index assessment died within 10 y of their illness as
      compared to only 7.3% who had no early damage (log rank P-value = 0.0002). SLE
      patients who died within 10 y were more likely to have renal damage (P = 0.013),
      and a trend toward more cardiovascular disease (P = 0.056), compared to patients
      who were alive. Early damage as reflected by the initial SLICC/ACR Damage Index
      is associated with a higher rate of mortality.

PMID- 11237133
TI  - FcgammaRIIa polymorphism in Japanese patients with systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is an immune complex-mediated disease and
      organ damage is caused by the deposition of immune complex. Receptors which
      recognize the Fc portion of immunoglobulin G (FcgammaR) play a key role in the
      phagocytosis of immune complexes. As the gene encoding for FcgammaR of class IIa
      (FcgammaRIIa) has two allelic forms, H131 and R131, which differ in their
      affinity to IgG2, this polymorphism might have implications in handling immune
      complex. We studied the distribution of the FcgammaRIIa polymorphism in 90
      Japanese patients with SLE. We also examined the association between FcgammaRIIa
      polymorphism and the disease activity of SLE and the histopathological findings
      of lupus nephritis. FcgammaRIIa polymorphism was determined by PCR and dot blot
      analysis. The allelic frequency of H131 in patients with SLE was significantly
      lower (H131/R131 = 0.44/0.56) than that of normal controls (H131/R131 =
      0.62/0.38; P < 0.05). No significant association was observed between FcgammaRIIa
      polymorphism and the clinical parameters for the activity of SLE. There was no
      association between FcgammaRIIa polymorphism and the histological findings in
      lupus nephritis. The difference in the distribution of FcgammaRIIa alleles
      between patients with SLE and normal subjects indicates that this polymorphism is
      a candidate of susceptibility gene for SLE in Japanese.

PMID- 11237134
TI  - The illness and death of a female hyena poisoned by zinc ingested as pennies.

PMID- 11237135
TI  - Evaluation of a multiple-antigen enzyme-linked immunosorbent assay for detection
      of Mycobacterium tuberculosis infection in captive elephants.
AB  - Mycobacterium tuberculosis has become an important agent of disease in the
      captive elephant population of the United States, although current detection
      methods appear to be inadequate for effective disease management. This
      investigation sought to validate a multiple-antigen enzyme-linked immunosorbent
      assay (ELISA) for screening of M. tuberculosis infection in captive elephants and
      to document the elephant's serologic response over time using a cross-sectional
      observational study design. Serum samples were collected from 51 Asian elephants
      (Elephas maximus) and 26 African elephants (Loxodonta africana) from 16 zoos and
      circuses throughout the United States. Infection status of each animal was
      determined by mycobacterial culture of trunk washes. Reactivity of each serum
      sample against six antigens was determined, and the linear combination of
      antigens that accurately predicted the infection status of the greatest number of
      animals was determined by discriminant analysis. The resulting classification
      functions were used to calculate the percentage of animals that were correctly
      classified (i.e., specificity and sensitivity). Of the 77 elephants sampled, 47
      fit the criteria for inclusion in discriminant analysis. Of these, seven Asian
      elephants were considered infected; 25 Asian elephants and 15 African elephants
      were considered noninfected. The remaining elephants had been exposed to one or
      more infected animals. The specificity and sensitivity of the multiple-antigen
      ELISA were both 100% (91.9-100% and 54.4-100%, respectively) with 95% confidence
      intervals. Mycobacterium bovis culture filtrate showed the highest individual
      antigen specificity (95%; 83.0-100%) and sensitivity (100%; 54.4-100%). Serum
      samples from 34 elephants were analyzed over time by the response to the culture
      filtrate antigen; four of these elephants were culture positive and had been used
      to calculate the discriminant function. Limitations such as sample size,
      compromised ability to ascertain each animal's true infection status, and absence
      of known-infected African elephants suggest that much additional research needs
      to be conducted regarding the use of this ELISA. However, the results indicate
      that this multiple-antigen ELISA would be a valuable screening test for detecting
      M. tuberculosis infection in elephant herds.

PMID- 11237136
TI  - Morbidity and mortality associated with a new mycoplasma species from captive
      American alligators (Alligator mississippiensis).
AB  - Nine of 74 American alligators (Alligator mississippiensis) from a captive
      Florida herd of 3-4-m-long, 200-350-kg, adult males greater than 30 yr of age
      died within a 10-day period during 1995. Nonspecific clinical signs included
      anorexia, lethargy, muscle weakness, paraparesis, bilateral white ocular
      discharge, and various degrees of periocular, facial, cervical, and limb edema.
      Pneumonia, pericarditis, and arthritis were found on postmortem evaluation of the
      spontaneously dead and euthanatized alligators. Rapidly growing mycoplasmas were
      identified by culture, and mycoplasma nucleotide sequences were identified by
      polymerase chain reaction testing of fresh lung and synovial fluid from an
      affected alligator. Culture of banked frozen lung from necropsy specimens and
      fresh lung and fresh synovial fluid from newly affected alligators confirmed the
      presence of a new mycoplasma species in seven of eight individuals.
      Oxytetracycline was administered, but related deaths continued for 6 mo until
      only 14 of the initial alligators remained. An enzyme-linked immunosorbent assay
      to detect antibody was developed, and the organism was transmitted experimentally
      to naive juvenile alligators, although the source of the organism, Mycoplasma sp.
      (ATCC 700619), has not been identified. The alligator isolate is a novel species
      in the mycoplasma family because its nucleotide sequence does not match those of
      over 75 characterized mycoplasma species. Such factors as population density,
      animal age, and mycoplasmal virulence likely contributed to the course of
      disease.

PMID- 11237137
TI  - Plasma fat-soluble vitamin and mineral concentrations in relation to diet in
      captive pteropodid bats.
AB  - Circulating plasma fat-soluble vitamin and mineral concentrations were compared
      in captive females of three species for fruit bats (Pteropus vampyrus, Pteropus
      hypomelanus, and Pteropus pumilus) fed the same diet. Daily total food intake
      averaged 28% of body weight on an as-fed basis or 7% on a dry matter basis.
      Dietary leftovers contained higher concentrations of phosphorus, magnesium, and
      zinc than the diet offered, suggesting some nutrient selectivity. Additionally,
      fecal mineral concentrations were two- to threefold higher than dietary
      concentrations of corresponding nutrients. Plasma concentrations of vitamin A
      (0.02-0.05 microg retinol/ml), vitamin D (1.50 ng 25-OH D3/ml; 93-108 pg 1,25
      diOH D3/ml), and vitamin E (0.49-1.05 microg alpha-tocopherol/ml) were lower than
      in other herbivorous mammals, whereas plasma mineral concentrations were within
      normal mammalian ranges. These data may help assess the nutritional status of
      fruit bats.

PMID- 11237138
TI  - Gastrointestinal parasites of mountain gorillas (Gorilla gorilla beringei) in the
      Parc National des Volcans, Rwanda.
AB  - Ninety-eight fecal samples were collected from 74 free-living mountain gorillas
      (Gorilla gorilla beringei) from the Parc National des Volcans, Rwanda, between
      July 1995 and January 1997 and examined for parasites by Sheather's sugar and
      zinc sulfate flotation methods, trichrome staining, and larval cultures. All
      samples contained at least one parasite. Seventeen endoparasites were identified,
      including eight protozoa, seven nematodes, one cestode, and one trematode. Two
      species of arthropod mite were also recovered from the fecal samples. Parasites
      observed on fecal examinations included strongyle/trichostrongyle-type eggs
      (72/74) (representing Oesphagostomum sp., Trichostrongylus sp., Hyostrongylus
      spp., and possibly Murshidia sp.), Strongyloides sp. (1/74), Trichuris trichiura
      (2/74), Probstmayria sp. (7/74), Anoplocephala sp. (63/74), Entamoeba hartmanni
      cysts and trophozoites (19/70), Endolimax nana cysts (31/70), Iodamoeba
      buetschlii cysts (11/70), Endolimax nana or Iodamoeba buetschlii trophozoites
      (63/70). Entamoeba coli cysts and trophozoites (14/70), Entamoeba histolytica
      trophozoite (1/70), Chilomastix sp. cysts and trophozoites (31/70), and Giardia
      sp. cysts (2/70). In addition, one ascarid and one trematode egg were seen. There
      were no significant differences in the prevalence of parasites between males and
      females and between age groups: however, infants and juveniles appeared to have a
      lower prevalence of Anoplocephala gorillae, and the silverbacked males appeared
      to have a higher prevalence of Probstmayria sp. Parasite prevalence was
      consistent among the five social groups studied except Susa group had a
      significantly lower prevalence of Anoplocephala gorillae. Trichuris trichiura,
      Strongyloides sp., Chilomastix sp., and Endolimax nana were identified for the
      first time in this population, and it is possible that these parasites were of
      human origin. Although there were no obvious clinical effects due to the presence
      of these parasites, six parasites identified (Trichuris trichiura, Strongyloides
      sp., Oesphagostomum sp., Trichostrongylus sp., Entamoeba histolytica, and Giardia
      sp.) could potentially be pathogenic. Some of the parasite products and cultured
      larvae could not be speciated.

PMID- 11237140
TI  - A survey of camel (Camelus dromedarius) diseases in Jordan.
AB  - Information on incidences of camel (Camelus dromedarius) diseases in Jordan is
      scarce. In this survey, 369 live and 156 slaughtered camels were examined in four
      Jordanian geographic regions and the proportion of diseased camels was
      calculated. Intestinal parasite ova were detected in 98% of camels; one or more
      species of external parasites were found on the skin of all camels; 33% had nasal
      myiasis; and hydatid cysts were identified in 44% of the slaughtered animals.
      Sarcoptic mange (Sarcoptes scabiei var. cameli) and trypanasomiasis, two diseases
      of economic importance, were also diagnosed in 83% and 33% of the 32 and 257
      examined camels, respectively. Rabies virus was detected in eight camels by use
      of fluorescent antibody examination of brain tissues. Foreign-body accumulation
      within the first and second stomach compartments was the predominant
      gastrointestinal disease of slaughtered adult camels (22%). Ten percent of
      slaughtered camels had bacterial pneumonia, with Pasteurella hemolytica most
      often isolated (56% of pneumonic lungs). Further investigation into the
      relationship between parasite burden and health in camels is required to assess
      the significance of the high prevalence of parasites.

PMID- 11237139
TI  - Cardiopulmonary and anesthetic effects of medetomidine-ketamine-butorphanol and
      antagonism with atipamezole in servals (Felis serval).
AB  - Seven (three male and four female) 4-7-yr old captive servals (Felis serval)
      weighing 13.7 +/- 2.3 kg were used to evaluate the cardiopulmonary and anesthetic
      effects of combined intramuscular injections of medetomidine (47.4 +/- 10.3
      microg/kg), ketamine (1.0 +/- 0.2 mg/kg), and butorphanol (0.2 +/- 0.03 mg/kg).
      Inductions were smooth and rapid (11.7 +/- 4.3 min) and resulted in good muscle
      relaxation. Significant decreases in heart rate (85 +/- 12 beats/min) at 10 min
      after injection and respiratory rate (27 +/- 10 breaths/min) at 5 min after
      injection continued throughout the immobilization period. Rectal temperature and
      arterial blood pressure did not change significantly. The PaO2 decreased
      significantly, and PaCO2 increased significantly during immobilization but
      remained within clinically acceptable limits. Hypoxemia (PaO2 < 60 mm Hg) was not
      noted, and arterial blood oxygen saturation (SaO2) was greater than 90% at all
      times. Relative arterial oxygen saturation (SpO2) values, indicated by pulse
      oximetry, were lower than SaO2 values. All animals could be safely handled while
      sedated. Administration of atipamezole (236.8 +/- 51.2 microg/kg half i.v. and
      half s.c.), an alpha2 antagonist, resulted in rapid (4.1 +/- 3 min to standing)
      and smooth recoveries.

PMID- 11237141
TI  - Hematology and blood biochemistry of captive mugger crocodiles (Crocodylus
      palustris).
AB  - Comprehensive hematologic and biochemical analyses were conducted on blood from
      23 male and 31 female clinically stable captive mugger crocodiles (Crocodylus
      palustris). Erythrocyte mean corpuscular volume (MCV), potassium, cholesterol,
      and calcium concentrations were significantly greater in juvenile males than in
      juvenile females, but no significant differences were determined between
      parameters of subadult males and subadult females. The mean WBC count and mean
      heterophil count were significantly higher in adult males than in adult females.
      Mean uric acid concentration was significantly greater in adult females than in
      males. Mean erythrocyte count was significantly higher in adults than in
      juveniles. Adult mean WBC and lymphocyte counts were significantly lower than
      those of both juveniles and subadults. Subadults had significantly lower mean
      eosinophil counts than both adults and juveniles. Subadults had significantly
      lower mean alkaline phosphatase activities than juveniles, whereas the adults had
      significantly lower aspartate aminotransferase and alanine aminotransferase
      activities than other groups. Lactate dehydrogenase activities were significantly
      lower for subadults than for juveniles and adults. Cholesterol concentrations
      were significantly higher for subadults and juveniles compared with adults.
      Triglyceride concentration was significantly lower for subadults and highest for
      juveniles. Glucose concentrations were significantly higher for adults. Blood
      urea nitrogen was significantly lower for subadults than for both adults and
      juveniles. Uric acid concentrations were significantly higher for juveniles than
      for the subadults and adults. The subadult animals also had a significantly lower
      potassium concentration. The results obtained were then compared with known
      values for other crocodilian species.

PMID- 11237142
TI  - Evaluation of anthelmintic activity in captive wild ruminants by fecal egg
      reduction tests and a larval development assay.
AB  - The effectiveness of anthelmintics was evaluated in four herds of captive
      ruminants, wapiti (Cervus elaphus), Armenian red sheep (Ovis orientalis), giraffe
      (Giraffa camelopardalis), and pronghorn (Antilocapra americana), by the use of
      fecal egg reduction tests (FERTs) and a commercial larval development assay (LDA)
      designed to evaluate susceptibility or resistance of nematodes to anthelmintics.
      Haemonchus sp. was the predominant nematode in the red sheep, giraffe, and
      pronghorn herds, whereas Ostertagia sp. and Trichostrongylus sp. were predominant
      in the wapiti. The LDA data indicated susceptibility by the worms to
      benzimidazoles except in the red sheep flock, which showed a high level of
      resistance. High levels of resistance to levamisole were seen in the worm
      populations from the wapiti and red sheep, moderate resistance in the pronghorn
      herd, and susceptibility in the giraffe herd. Worms were susceptible in all four
      herds to a combination of benzimidazole/levamisole. There was suspected
      avermectin resistance by Trichostrongylus sp. in the wapiti herd and by
      Haemonchus sp. in the giraffe. The FERTs agreed with the LDA in showing the
      Haemonchus in the giraffe was susceptible to fenbendazole and had suspected
      resistance to ivermectin, whereas Haemonchus in the red sheep and pronghorn were
      susceptible to ivermectin. There was correlation between the tests evaluating
      anthelmintics. The LDA is useful as a screening test in the selection of an
      anthelmintic for use in grazing ruminants, but the effectiveness of a drug in a
      host species may depend as much on the dose used, and the method of
      administration, as it does on the parasite's sensitivity to the anthelmintic.

PMID- 11237143
TI  - A longitudinal study of Escherichia coli strains isolated from captive mammals,
      birds, and reptiles in Trinidad.
AB  - A longitudinal study was conducted of the prevalence and characteristics of
      Escherichia coli in mammals, birds, and reptiles housed at the Emperor Valley
      Zoo, Trinidad. During a 6-mo study period, swabs were obtained from fecal samples
      that were randomly collected from the enclosures of animals from these three
      taxonomic groups every 3 wk. With snakes, both cloacal and fecal swabs were
      obtained. Fecal and cloacal swabs were cultured for E. coli on eosin methylene
      blue agar. The production of mucoid colonies and hemolytic colonies and non
      sorbitol fermenter status were identified. The occurrence of O157 strains was
      determined amongst E. coli isolates that were non-sorbitol fermenters, and the
      disc diffusion method was used to determine the antibiograms of isolates. The
      frequency of E. coli isolation was significantly higher in mammals compared with
      birds and reptiles. Overall, the frequencies of isolation of E. coli from
      omnivores. herbivores, and carnivores, 87.2%, 70.0%, and 57.3%, respectively,
      regardless of animal class, were significantly different. Most (99.6%) of the E.
      coli isolates tested for antibiotic sensitivity exhibited resistance to one or
      more of the eight antimicrobial agents used. The possession of phenotypic
      virulence markers by the E. coli isolates studied and the generally high
      resistance to antimicrobial agents may have health implications for the
      zoological collection.

PMID- 11237144
TI  - Management and prevention of vitamin D deficiency rickets in captive-born
      juvenile chimpanzees (Pan troglodytes).
AB  - Vitamin D deficiency rickets was diagnosed in three juvenile chimpanzees (Pan
      troglodytes) raised indoors under skylights and consuming only breast milk. Two
      cases detected early had mild but characteristic radiographic changes. More
      advanced disease presented with florid x-ray features of rickets and pathologic
      fractures, as well as hypocalcemia, hypophosphatemia, and low serum 25
      hydroxyvitamin D levels. Treatment by a single injection of vitamin D2 in sesame
      oil (slow release) followed by daily oral supplementation with vitamin D2
      corrected the condition. On the basis of experience with these cases and
      comparison with rickets in humans, a prevention protocol for mother-reared,
      inside-housed, chimpanzee juveniles was developed. Injection with slow release
      vitamin D2 (5,000 IU i.m. once) at 4 mo of age, followed by oral supplementation
      of 400 IU vitamin D2 daily until weaning, prevents rickets in juvenile
      chimpanzees raised indoors.

PMID- 11237145
TI  - An epizootic of adenovirus-induced hemorrhagic disease in captive black-tailed
      deer (Odocoileus hemionus).
AB  - Ten fawns and four adult black-tailed deer (Odocoileus hemionus) in a captive
      herd died as a result of adenovirus-induced hemorrhagic disease. Acute, systemic
      infections were characterized by hemorrhagic enteropathy, pulmonary edema, and
      occasional ulceration of the upper alimentary tract. Localized infections were
      limited to the upper alimentary tract and included stomatitis, pharyngitis,
      mandibular osteomyelitis, and rumenitis. In deer with acute, systemic infections,
      a diagnosis was made by histopathology and immunohistochemistry. The serum
      neutralization test was useful for confirming a diagnosis in animals with
      prolonged, localized infections. Deer originating from herds with a history of
      adenovirus infection should not be transferred to other captive herds or released
      into free-ranging populations because they may serve as carriers of adenovirus.

PMID- 11237146
TI  - Fungal dermatitis in captive pinnipeds.
AB  - Fungal dermatitis was diagnosed in two captive gray seals (Halichoerus grypus)
      and four harbor seals (Phoca vitulina) between 1992 and 1994. Trichophyton
      mentagrophytes, Malassezia spp., and Yarrowia (Candida) lipolytica were isolated.
      Erythematous, thickened, alopecic skin lesions were present on the face and on
      the flippers, particularly around the nail bed. The two most important
      environmental factors associated with development of fungal dermatitis appeared
      to be excessive chlorination of pool water and warm water temperature.

PMID- 11237147
TI  - Hiatal hernia and diaphragmatic eventration in a leopard (Panthera pardus).
AB  - A 1-yr-old male leopard (Panthera pardus) presented for intermittent anorexia,
      emaciation, and generalized muscle wasting. Plain radiographs, ultrasonography,
      and esophageal endoscopy led to a diagnosis of diaphragmatic eventration with
      probable concurrent hiatal hernia. An exploratory laparotomy confirmed both
      diagnoses, and surgical repair and stabilization were performed. After surgery,
      the leopard was maintained on small liquid meals for 4 days, with a gradual
      return to normal diet over 2 wk. By 4 wk after surgery, the leopard was eating
      well and gaining weight, and it showed no recurrence of clinical signs for 2 yr
      subsequently, becoming mildly obese.

PMID- 11237148
TI  - Sarcocystis neurona-like encephalitis in a Canada lynx (Felis lynx canadensis).
AB  - A 13-yr-old female Canada lynx (Felis lynx canadensis) died after a short
      clinical illness, and necropsy revealed multifocal, nonsuppurative encephalitis
      with protozoal schizonts present in cerebral vascular endothelial cells. The
      schizonts stained immunohistochemically with antiserum to Sarcocystis neurona.
      This is the first report of Sarcocystis encephalitis in the Canada lynx.

PMID- 11237149
TI  - Treatment of fibrosarcoma in a maned wolf (Chrysocyon brachyurus) by rostral
      maxillectomy.
AB  - A 12-yr-old captive intact male maned wolf (Chrysocyon brachyurus) was diagnosed
      with a fibrosarcoma of the incisive bones. The mass was excised by rostral
      maxillectomy, and the wolf remained normal and on display with good function and
      cosmetics for 7 mo. Subsequently, it became weak, ataxic, and dyspneic and was
      euthanatized. At necropsy, there was a small regrowth of the maxillary tumor, a
      metastatic mediastinal mass, and multiple metastatic lung masses, suggesting that
      oral fibrosarcoma in maned wolves behaves similarly to oral fibrosarcoma in
      domestic canines. Aggressive surgical treatment of oral fibrosarcoma in this
      species can achieve good functional and cosmetic results.

PMID- 11237150
TI  - Diagnosis and treatment of a fractured third phalanx in a Masai giraffe (Giraffe
      camelopardalis tippelskirchi).
AB  - A 10-yr-old male Masai giraffe (Giraffe camelopardalis tippelskirchi) presented
      with acute right forelimb lameness. Radiographs revealed a fracture of the medial
      claw of the distal phalanx penetrating into the distal interphalangeal joint. The
      giraffe was sedated while it was standing in a chute, and a wooden "hoof block"
      was applied to the lateral claw of the same limb. The animal was no longer lame 3
      days after the procedure. Subsequent treatments included vitamin E,
      phenylbutazone, and glycosaminoglycans. For 7 wk it was maintained in a small
      holding yard on packed sand during the day and on deep sand during the night. The
      hoof block slowly wore down, and at 7 wk, it was placed back on concrete in the
      evening. At 8 wk, the block had completely worn off and the animal was no longer
      lame, but radiographs indicated minimal fracture healing. Radiographs performed
      at 7 mo indicated that there was still a radiolucent zone at the fracture line
      but calcification was evident at the margins of the fracture.

PMID- 11237151
TI  - Caudal cervical disc protrusion in a Bengal tiger (Panthera tigris tigris).
AB  - A young adult male white Bengal tiger (Panthera tigris tigris) presented with
      hindlimb ataxia. Cervical and lumbar myelography revealed a compressive lesion of
      the cord at C(6-7). Corticosteroid therapy and confinement failed to provide
      lasting remission of signs. A modified, inverted cone ventral slot decompression
      was used to remove the fibrous material causing cord compression at C(6-7).
      Temporary Horner's syndrome and laryngeal paresis developed postsurgically
      because of excessive tissue retraction. The animal recovered normal ambulatory
      function 6 wk after surgery.

PMID- 11237152
TI  - Ventricular septal defect in a blue duiker (Cephalophus monticola).
AB  - A 9-mo-old female blue duiker (Cephalophus monticola) weighing 3.9 kg was
      diagnosed with a cardiac murmur during quarantine examination. Evaluation of the
      heart by auscultation, electrocardiography, two-dimensional echocardiography, and
      Doppler color-flow echocardiography revealed a restrictive outlet ventricular
      septal defect with left atrial and left ventricular dilation. Trivial mitral,
      tricuspid, and aortic regurgitation was also noted. Though the duiker was
      clinically asymptomatic at the time of cardiac evaluation, it was found dead 1 wk
      later. The cause of death was not determined.

PMID- 11237153
TI  - Clinical presentation and antiviral therapy for poxvirus infection in pudu (Pudu
      puda).
AB  - A severe poxvirus infection occurred in three pudu (Pudu puda), resulting in two
      fatalities. Cutaneous ulcers with mucopurulent exudate were present around the
      eyes and nose, at the lip margins, coronary bands, and teats. Mucosal ulcers were
      present in the oral cavity, esophagus, and forestomachs. In the two fatalities, a
      secondary disseminated fungal infection also occurred. Affected animals were
      leukopenic, hypocalcemic, and hyperphosphatemic and had elevated serum alkaline
      phosphatase, alanine aminotransferase, and aspartate aminotransferase levels.
      Electron microscopic examination of affected skin confirmed the presence of a
      poxvirus. Neutralizing antibody titers to this virus were present in the two pudu
      tested. One case was treated with cidofovir, 5 mg/kg i.v. q7d for four
      treatments. Complete recovery occurred in the treated animal. This is the second
      report of poxvirus infection in pudu and the first report describing clinical
      presentation, presence of secondary disseminated fungal infection, and successful
      treatment.

PMID- 11237154
TI  - Clinical challenge. Diagnosis: oral mass; compound odontoma.

PMID- 11237155
TI  - Research into the black box of rehabilitation: the risks of a Type III error.
AB  - Type I and Type II errors in the interpretation of data from clinical trials
      concern statistical matters, and the probability of drawing erroneous conclusions
      from inadequate data. However in rehabilitation research a third possible error
      may arise. Successful rehabilitation depends upon the co-ordinated work of an
      expert multidisciplinary team, and can be considered as a network involving a
      whole system. Demonstrating that one part of that system looked at in isolation
      does not have the expected effect does not prove that the specific part is not
      necessary to the success of the whole system. The isolated intervention may still
      have an important effect when interacting with other variables or interventions.
      Failure to consider the interactive effects of an intervention might constitute a
      Type III interpretation error.

PMID- 11237156
TI  - Adapting the Nottingham Health Profile for use in people with severe physical
      disabilities.
AB  - BACKGROUND: The Nottingham Health Profile (NHP) is a well-known quality of life
      questionnaire. However, wheelchair-bound patients might obtain misleading scores
      on the scales Physical mobility, Pain and Emotional reactions. We tested three
      possible adaptations of the Dutch NHP to overcome this problem. METHODS:
      Respondents were 111 wheelchair-using people (walking ability maximum 5 m) with
      spinal cord injury, rheumatic diseases and other diagnoses. Adaptation methods
      were formulation of new questions (Q-NHP), a recoding procedure (R-NHP) and
      deleting items (D-NHP). Internal consistency, correlations between original and
      adapted scales and correlations with upper and lower extremity function and
      social functioning (NHP part II) were computed. RESULTS: All adapted Pain and
      Emotional reactions scales were close to the original ones. The original Physical
      mobility scale proved invalid, resulting in better median scores for those
      patients who could not walk at all (38.7) than for patients who could walk a bit
      (50.0). The Q-NHP performed little better than the original one and suffered from
      greater complexity. The R-NHP showed better internal consistency (0.69 versus
      0.49) and construct validity than the D-NHP. CONCLUSION: An uncomplicated
      recoding procedure, scoring five questions about walking problems as 'yes' if
      respondents confirmed the question 'I cannot walk at all', improved reliability
      and validity of the Dutch NHP. Use of this recoding procedure in future research
      using the NHP is recommended, although its applicability in other language
      versions has to be proven in future research.

PMID- 11237157
TI  - The Bobath concept.

PMID- 11237158
TI  - Exercise therapy for arm function in stroke patients: a systematic review of
      randomized controlled trials.
AB  - OBJECTIVE: Assessment of the available evidence for the effectiveness of exercise
      therapy to improve arm function in patients who have suffered from a stroke.
      METHODS: A systematic search of bibliographical databases and reference checking
      were performed to identify publications on randomized controlled trials (RCTs)
      which evaluated the effect of exercise therapy on arm function in stroke
      patients. The methodological quality was assessed systematically by two raters,
      based on a standardized list of methodological criteria. Study characteristics,
      such as the chronicity and severity of impairment of the patient population, the
      amount and duration of interventions, and specific methodological criteria, were
      related to reported effects. RESULTS: Thirteen RCTs were identified, six of which
      reported positive results on an arm function test. In five of these six studies
      there was a contrast in amount or duration of exercise therapy between groups.
      Methodological scores ranged from 5 to 15 (maximum possible score: 19 points).
      CONCLUSION: Insufficient evidence made it impossible to draw definitive
      conclusions about the effectiveness of exercise therapy on arm function in stroke
      patients. The difference in results between studies with and without contrast in
      the amount or duration of exercise therapy between groups suggests that more
      exercise therapy may be beneficial.

PMID- 11237159
TI  - The COSTAR wheelchair study: a two-centre pilot study of self-propulsion in a
      wheelchair in early stroke rehabilitation. Collaborative Stroke Audit and
      Research.
AB  - OBJECTIVE: It is uncertain whether self-propulsion in a wheelchair should be
      encouraged or discouraged in the early stages of stroke rehabilitation. DESIGN: A
      two-centre pilot study to assess the feasibility of performing a multicentre
      randomized controlled trial on this subject. SETTING: Clatterbridge and Aintree
      Stroke Rehabilitation Units, Merseyside, UK. SUBJECTS: Forty early stroke
      patients (mean age 67 years) in whom it was uncertain whether self-propulsion in
      a wheelchair should be encouraged were studied. INTERVENTION: A central
      randomization service at Newcastle University was used to determine the policy
      about wheelchair provision and use for each patient. They were allocated to
      either an 'encouraged to self-propel' or a 'discouraged from self-propulsion
      group'. OUTCOME MEASURES USED: Independent outcome assessment was performed by
      postal questionnaire and telephone interview using the Barthel ADL Scale,
      Nottingham Extended ADL Scales and the shortened General Health Questionnaire
      (GHQ-12) at 3 and 12 months. Patient's length of stay and their Ashworth tone
      score were also measured either at three months or when they were discharged from
      hospital. RESULTS: After considerable preparation time it was possible to conduct
      a trial on self-propulsion in early stroke rehabilitation in the two-pilot
      centres. No major differences were found between the pilot groups for any of the
      outcome measures. CONCLUSIONS: A multicentre randomized controlled trial to
      assess this question is feasible but further work is being conducted before
      proceeding, to satisfy the concerns expressed to our group regarding the
      appropriateness of the intervention and the outcome measures.

PMID- 11237160
TI  - A multicentre randomized controlled trial of leisure therapy and conventional
      occupational therapy after stroke. TOTAL Study Group. Trial of Occupational
      Therapy and Leisure.
AB  - OBJECTIVE: To evaluate the effects of leisure therapy and conventional
      occupational therapy (OT) on the mood, leisure participation and independence in
      activities of daily living (ADL) of stroke patients 6 and 12 months after
      hospital discharge. DESIGN: Multicentre randomized controlled trial. SETTING AND
      PARTICIPANTS: Four hundred and sixty-six stroke patients from five UK centres.
      MAIN OUTCOME MEASURES: The General Health Questionnaire (12 item), the Nottingham
      Extended ADL Scale and the Nottingham Leisure Questionnaire, assessed by post,
      with telephone clarification. RESULTS: Four hundred and forty (94%) and 426 (91%)
      subjects were alive at 6 and 12 months, respectively. Three hundred and seventy
      four (85% of survivors) and 311 (78% of survivors) responded at 6 and 12 month
      follow-up respectively. At six months and compared to the control group, those
      allocated to leisure therapy had nonsignificantly better GHQ scores (-1.2: 95% CI
      -2.9, +0.5), leisure scores (+0.7, 95% CI -1.1, +2.5) and Extended ADL scores
      (+0.4: 95% CI -3.8, +4.5): the ADL group had nonsignificantly better GHQ scores (
      0.1: 95% CI -1.8, +1.7) and Extended ADL scores (+1.4: 95% CI -2.9, +5.6) and
      nonsignificantly worse leisure scores (-0.3: 95% CI -2.1, +1.6). The results at
      12 months were similar. CONCLUSION: In contrast to the findings of previous
      smaller trials, neither of the additional OT treatments showed a clear beneficial
      effect on mood, leisure activity or independence in ADL measured at 6 or 12
      months.

PMID- 11237161
TI  - Electrical stimulation for preventing and treating post-stroke shoulder pain: a
      systematic Cochrane review.
AB  - BACKGROUND: Shoulder pain after stroke is common and disabling. The optimal
      management is uncertain, but electrical stimulation (ES) is often used to treat
      and prevent pain. OBJECTIVES: The objective of this review was to determine the
      efficacy of any form of surface ES in the prevention and/or treatment of pain
      around the shoulder at any time after stroke. SEARCH STRATEGY: We searched the
      Cochrane Stroke Review Group trials register and undertook further searches of
      Medline, Embase and CINAHL. Contact was established with equipment manufacturers
      and centres that have published on the topic of ES. SELECTION CRITERIA: We
      considered all randomized trials that assessed any surface ES technique
      (functional electrical stimulation (FES), transcutaneous electrical nerve
      stimulation (TENS) or other), applied at any time since stroke for the purpose of
      prevention or treatment of shoulder pain. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently selected trials for inclusion, assessed trial quality and
      extracted the data. MAIN RESULTS: Four trials (a total of 170 subjects) fitted
      the inclusion criteria. Study design and ES technique varied considerably, often
      precluding the combination of studies. Population numbers were small. There was
      no significant change in pain incidence (odds ratio (OR) 0.64; 95% CI 0.19-2.14)
      or change in pain intensity (standardized mean difference (SMD) 0.13; 95% CI -1.0
      1.25) after ES treatment compared with control. There was a significant treatment
      effect in favour of ES for improvement in pain-free range of passive humeral
      lateral rotation (weighted mean difference (WMD) 9.17; 95% CI 1.43-16.91). In
      these studies ES reduced the severity of glenohumeral subluxation (SMD -1.13; 95%
      CI -1.66 to -0.60), but there was no significant effect on upper limb motor
      recovery (SMD 0.24; 95% CI -0.14-0.62) or upper limb spasticity (WMD 0.05; 95% CI
      -0.28-0.37). There did not appear to be any negative effects of electrical
      stimulation at the shoulder. REVIEWERS' CONCLUSIONS: The evidence from randomized
      controlled trials so far does not confirm or refute that ES around the shoulder
      after stroke influences reports of pain, but there do appear to be benefits for
      passive humeral lateral rotation. A possible mechanism is through the reduction
      of glenohumeral subluxation. Further studies are required.

PMID- 11237162
TI  - The effect of a hinged ankle foot orthosis on hemiplegic gait: objective measures
      and users' opinions.
AB  - OBJECTIVE: To assess the effect of a hinged ankle foot orthosis (AFO) on
      functional mobility and gait impairments in people with a severe hemiplegia
      undergoing rehabilitation, and to investigate the patients' views of the hinged
      AFO. DESIGN: With/without group comparison, and face-to-face questionnaire.
      SUBJECTS AND SETTING: Twenty-five subjects over 18 years, with a hemiplegia
      following cerebrovascular accident (CVA) undergoing rehabilitation in a regional
      rehabilitation unit. OUTCOME MEASURES: Functional Ambulation Categories as a
      measure of disability. Paper walkways to measure gait impairments--stride length,
      step length, symmetry, cadence and velocity. Face-to-face questionnaire to
      determine the users' opinion of the hinged AFO. RESULTS: Comparison of gait with
      and without the hinged AFO showed significant improvements in functional mobility
      (p = 0.000) and in some gait impairments; stride length of the weak (p < 0.005,
      95% CI -8.1, -1.6) and sound legs (p < 0.014, 95% CI -8, -1), velocity (p = 0.00,
      95% CI -0.1, -0.03) and cadence (p < 0.002, 95% CI -15.1, -3.8). No effect was
      found for step length in the weak or sound leg or symmetry. The subjects'
      response was positive, 24 (96%) felt they walked better with the AFO and found it
      comfortable. Twenty-three (92%) were unbothered by the appearance and 16 (64%)
      could doff and don it. CONCLUSION: The hinged AFO improved objective measures of
      gait impairments and disability and patients were positive about it.

PMID- 11237163
TI  - Patterns of hemiparesis recovery in lacunar and partial anterior circulation
      infarct stroke syndromes.
AB  - OBJECTIVE: To investigate patterns of hemiparesis recovery in lacunar (LACI) and
      partial anterior circulation infarct (PACI) stroke syndromes. DESIGN: Prospective
      observational study. SETTING: District general hospital and stroke rehabilitation
      ward. SUBJECTS: Forty-seven patients (25 LACI and 22 PACI) with a first-ever
      stroke causing a hemiplegia. Average age 76.4 years (range 59-88). MEASURES:
      Outcome measures assessed disability (Barthel Index), limb power (Motricity
      Index) and mobility (Rivermead Mobility Index) at baseline and 3, 6, 9, 12, 16
      and 24 weeks post stroke onset. RESULTS: The time to maximum recovery, time to
      50% recovery and area under the recovery curve was determined for each of the
      outcome measures. There were no statistical differences between these recovery
      parameters between the PACI and LACI stroke syndromes. CONCLUSION: Classification
      of hemiplegic stroke into PACI or LACI syndromes does not distinguish distinctive
      recovery patterns.

PMID- 11237164
TI  - Unpacking the black box of nursing and therapy practice for post-stroke shoulder
      pain: a precursor to evaluation.
AB  - OBJECTIVES: To describe current nursing and therapy interventions for the
      prevention and treatment of post-stroke shoulder pain and to explore the extent
      of their reported use in England. DESIGN: Semi-structured, the med interviews
      followed by a postal questionnaire. PARTICIPANTS: Six nurses, five occupational
      therapists (OTs) and six physiotherapists (PTs) were interviewed. Twelve nurses,
      12 OTs and 12 PTs were sent the pilot questionnaire and the main questionnaire
      was posted to 332 nurses, 332 OTs and 332 PTs. SETTING: NHS Trusts in England
      which provide acute stroke care/rehabilitation. PROCEDURE: Two researchers
      independently condensed the transcripts of the interviews into a list of
      interventions which were then transformed into a pilot postal questionnaire.
      Following the pilot small changes were made. Participants sent the main
      questionnaire were given three weeks to return it before being posted a reminder.
      After a further two weeks a researcher gave a telephone reminder. RESULTS: One
      hundred and seventy-five different types of interventions were identified. The
      main questionnaire (57.8% response rate) found that all of the interventions were
      used by at least one respondent and that only 22.9% of the interventions were
      used to the same extent by nurses, OTs and PTs. The data also suggest variation
      in reported use within professions. CONCLUSIONS: This study has found a large
      number of interventions for post-stroke shoulder pain which are reported to be
      used. This might reflect different causes of shoulder pain or variation between
      clinicians. Answers to these questions are expected to guide future evaluative
      research.

PMID- 11237165
TI  - Functional level of young adults with cerebral palsy.
AB  - OBJECTIVE: To acquire insight into the level of functioning of young adults with
      cerebral palsy (CP). DESIGN: Descriptive cross-sectional study. SETTING:
      Rehabilitation Centre Den Haag, The Netherlands. METHOD: A structured
      questionnaire, including the Barthel Index was mailed to 134 young adults (aged
      21-31 years) with cerebral palsy. RESULTS: Eighty subjects responded (60%). Of
      these, 60 (75%) were largely or fully independent in activities of daily living,
      72 (90%) moved independently indoors, 56 (70%) outdoors. In 67 (77.5%) of the
      group the level of communication was adequate for telephone conversation. Twenty
      four (30%) lived with their parents, 10 (12.5%) with a partner and 26 (32.5%)
      lived alone. Almost half lived in an unadapted house. Forty-two (53%) completed
      some form of secondary education and 29 (36.3%) had paid employment. CONCLUSION:
      Despite their considerable impairments, the large majority of this group of young
      adults with cerebral palsy are independent in activities of daily living,
      mobility and communication. Regarding the level of education, participation in
      paid employment and sports activities, however, young adults with CP are poorly
      integrated.

PMID- 11237166
TI  - Mobility of people with lower limb amputations: scales and questionnaires: a
      review.
AB  - OBJECTIVE AND DESIGN: A systematic literature review to compare mobility scales
      used for lower limb amputees. A literature search was carried out by computerized
      search of biomedical literature including Medline and Embase. The studies
      included were published between 1978 and 1998 and including the following
      keywords: amputation, artificial limbs, prosthesis, lower limb, activities of
      daily living, mobility. RESULTS: Thirty-five studies were identified; 19 had a
      measurement of separate levels of mobility comparable to each other. Sixteen
      studies used ordinal and ratio scales without separate levels of mobility. The
      widest range of measurement found was the scale from 'walking with prosthesis
      without a walking aid' to 'totally confined to bed'. The Stanmore Harold Wood
      mobility scale was published most frequently. None of the 35 studies presented
      give a continuous measurement of mobility. CONCLUSION: A multitude of measurement
      scales and questionnaires are available for differ in methods and measuring
      range. Measuring mobility by a scale has been shown to have limitations. Several
      authors did extensive research but they all measure only a number of aspects of
      mobility. Consensus about the measurement of mobility of lower limb amputees is
      not available in the recent literature.

PMID- 11237167
TI  - Carotenoids and retinoids as suppressors on adipocyte differentiation via nuclear
      receptors.
AB  - The adipocyte differentiation program is regulated by the sequential expression
      of transcriptional activators, mainly peroxisome proliferator activated receptor
      (PPAR) families. In the present study, we have decided to systematically examine
      the effects of vitamin A and its precursors, carotenoids and retinoids, on
      terminal differentiation from preadipocytes to adipocytes on the cellular and
      molecular aspects. The effects of active form of vitamin A, retinoic acid (RA),
      are believed to be mediated by specific nuclear receptor proteins [retinoic acid
      receptor (RAR)] which are members of the steroid and thyroid/retinoid receptor
      superfamily of ligand dependent transcriptional regulators, RARalpha, RARgamma,
      RXRalpha, and RXRbeta mRNA were abundant in adipose tissue and 3T3-L1 adipose
      cells. The autoregulated amplification of RARgamma mRNA was observed by these own
      ligands in 3T3-L1 cells. And, RA inhibited PPARgamma2 expression more effectively
      and caused concomitantly a greater inhibition of adipocyte differentiation. These
      results suggest that the inhibitory action of adipocyte differentiation by
      carotenoids and retinoids are exhibited through the RAR up-regulation and the
      suppression of PPARgamma2. The nature of the cross talk of vitamin A actions
      between the RARs, RXRs and PPARs via co-activator in adipose tissue will likely
      prove to be important for understanding the process of adipogenesis.

PMID- 11237168
TI  - Recent progress in carotenoid research on human diseases.

PMID- 11237169
TI  - Proanthocyanidins and human health: systemic effects and local effects in the
      gut.
AB  - Proanthocyanidins share common properties with other polyphenols, in particular
      their reducing capacity and ability to chelate metal ions. However, their
      polymeric nature clearly makes them different. They have a high affinity for
      proteins and their absorption through the gut barrier is likely limited to the
      molecules of low polymerization degree and to the metabolites formed by the
      colonic microflora, as suggested by in vitro experiments. The nutritional
      significance of proanthocyanidins is discussed in relation to their physico
      chemical properties and bioavailability.

PMID- 11237170
TI  - Chemistry and function of vegetable polyphenols with high molecular weights.
AB  - Structure and function of polypehnols with high molecular weights (tannins) were
      briefly reviewed to better understand the significance of polyphenol-rich foods
      and beverages. In a survey of bioactive ellagiannins with a macrocyclic structure
      and/or a gluconic acid core, some new oligomeric ellagitannins (eucarpanins and
      elaeagnatins) have been found in species of Myrtaceae and Elaeagnaceae, and their
      structures were elucidated by spectroscopic and chemical methods. Cytotoxic
      activity against human oral tumor cell lines and antibacterial activity against
      Helicobacter pylori have been evaluated for the ellagitannins obtained from both
      plants, and related compounds. The macrocyclic dimers, oentothein B, camelliin B
      and woodfordin C showed a remarkable cytotoxicity against human oral squamous
      cell carcinoma, but not against normal cells. These active tannins induced
      apoptosis of tumor cells. A potent antibacterial activity against Helicobacter
      pylori was exhibited by monomeric ellagitannins such as tellimagrandin I and
      stricitinin.

PMID- 11237171
TI  - Black and green tea and heart disease: a review.
AB  - Tea is the second most consumed beverage around the world behind water.
      Epidemiological evidence points to both green and black tea consumption being
      protective with respect to heart disease. However, epidemiological evidence does
      not prove cause and effect and is potentially flawed by confounding variables.
      The recent evidence with respect to teas' beneficial effects from in vitro and in
      vivo studies in both animals and humans will be covered in this review. The
      comparative benefits of green vs. black tea will be considered. Articles
      published through December, 1999 will be included.

PMID- 11237172
TI  - The role of anthocyanins as an antioxidant under oxidative stress in rats.
AB  - Cyanidin 3-O-beta-D-glucoside (C3G) is included in anthocyanins, and expected to
      have a potency to scavenge active oxygen species in vivo. Rats were fed a diet
      containing C3G (2 g/kg diet) for 14 days, and then subjected to hepatic ischemia
      reperfusion (I/R) as an oxidative stress model. I/R treatment elevated the liver
      thiobarbituric acid-reactive substance concentration and the serum activities of
      marker enzymes for liver injury, and lowered the liver reduced glutathione
      concentration. Feeding C3G significantly suppressed these changes caused by
      hepatic I/R. These results indicate that C3G functions as a potent antioxidant in
      vivo under oxidative stress. To clarify the mechanism of action of C3G, we
      investigated the absorption and metabolism of C3G in rats. C3G appeared in the
      plasma immediately after the oral administration of C3G. Protocatechuic acid,
      which seems to be produced by the degradation of cyanidin, was also present in
      the plasma. In the liver and kidneys, C3G was metabolized to methylated form.

PMID- 11237173
TI  - Phenolic antioxidants from herbs and spices.
AB  - Spices and herbs are recognized as sources of natural antioxidants and thus play
      an important role in the chemoprevention of diseases resulting from lipid
      peroxidation. Our studies on spices and herbs have given us over a hundred
      compounds, known and new, having high antioxidant activity. From the Labiatae
      family, Rosmarinus officinalis, Thymus vulgaris, Origanum vulgare and O. majorana
      gave 26 active comopounds. Over 40 antioxidative compounds from Zingiber
      officinale, 26 compounds from Curcuma domestica = C. longa, C. xanthorrhiza and
      Z. cassumunar were determined, these belonging to the family Zingiberaceae. From
      the family Myrtaceae, 25 compounds from the berries of Pimenta dioica were
      determined and 3 carbazoles were isolated from Murraya koenigii. Structure
      activity relationships of some of the isolated compounds were also discussed.

PMID- 11237174
TI  - Affinity of polyphenols for lipid bilayers.
AB  - Interaction of tea catechins with lipid bilayers has been investigated with
      liposome systems. Epicatechin gallate had the highest affinity for lipid
      bilayers, followed by epigallocatechin gallate, epicatechin, and
      epigallocatechin. Epicatechin gallate and epigallocatechin gallate in the surface
      of lipid bilayer perturbed the membrane structure.

PMID- 11237175
TI  - Dietary docosahexaenoic acid does not promote tissue lipid peroxide formation to
      the extent expected from the peroxidizability index of the lipids.
AB  - Changes in susceptibility of tissues to lipid peroxidation were investigated in
      rats after ingestion of oxidation-prone docosahexaenoic acid (C22:6n-3). Lipid
      peroxide levels in the liver, kidney and testis increased concomitant with
      increases in the peroxidizability indices calculated from the fatty acid
      composition of tissue total lipids. However, even in these cases, the lipid
      peroxides were not increased to the levels expected from the peroxidizability
      indices of these tissues, and thus no tissue injury was recognized. When low
      level of vitamin E was given to rats, the lipid peroxide levels of liver, kidney
      and testis nearly coincided with the peroxidizability indices of these tissues,
      where the cell injuries were observed as well. The mechanisms of defense to
      suppress lipid peroxide levels below the peroxidizability indices in normal
      vitamin E administration were presumed to be due to enhanced antioxidative
      function in the tissues mediated primarily by vitamin E, ascorbic acid and
      glutathione, and also to increased incorporation of docosahexaenoic acid into
      neutral lipids and phosphatidylethanolamine in the tissues, probably leading to
      acquiring stability against oxidative attack. Owing to these suppressive
      mechanisms, physiological efficacy of n-3 fatty acids may be exerted effectively.

PMID- 11237176
TI  - Recent studies on the biofunctions and biotransformations of curcumin.
AB  - Curcumin is a major component of Curcuma species, which is commonly used as a
      yellow coloring and flavoring agent in foods. Curcumin has shown anti
      carcinogenic activity in animals as indicated by its ability to block colon tumor
      initiation by azoxymethane and skin tumor promotion induced by phorbol ester TPA.
      Curcumin possesses anti-inflammatory activity and is a potent inhibitor of
      reactive oxygen-generating enzymes such as lipoxygenase/cyclooxygenase, xanthine
      dehydrogenase/oxidase and inducible nitric oxide synthase. Curcumin is also a
      potent inhibitor of protein kinase C, EGF-receptor tyrosine kinase and IkappaB
      kinase. Subsequently, curcumin inhibits the activation of NFkappaB and the
      expressions of c-jun, c-fos, c-myc and iNOS. It is proposed that curcumin may
      suppress tumor promotion through blocking signal transduction pathways in the
      target cells. Curcumin was first biotransformed to dihydrocurcumin and
      tetrahydrocurcumin and that these compounds subsequently were converted to
      monoglucuronide conjugates. These results suggest that curcumin-glucuronide,
      dihydro-curcumin-glucuronide, tetrahydrocurcumin-glucuronide and
      tetrahydrocurcumin are major metabolites of curcumin in mice.

PMID- 11237177
TI  - Chemistry and antioxidative factors in rosemary and sage.
AB  - Rosemary and sage are common spices used in food. In our recent search of cancer
      chemopreventive agents from spices, the alcohol extracts of rosemary and sage
      showed strong antumorigenic activities. Rosemary and sage extracts contain active
      antioxidative factors such as phenolic diterpenes, flavonoids and phenolic acids.
      Here we discuss chromatographic methods used to separate and purify compounds
      from these spices and MS and NMR spectrometry to identify the isolated compounds.
      Several new compounds isolated from sage were determined to be 6-O-caffeoyl-beta
      D-fructofuranosyl-(2-->1)-beta-glucopyranoside, 1-O-caffeoyl-beta-D-apiofuranosyl
      (1-->6)-beta-D-glucopyranoside, 1-O-p-hydroxybenzoyl-beta-D-apiofuranosyl-(1-->6)
      beta-D-glucopyranoside, 1-O-(3-methyl-2,3,4-trihydroxybutyl)-6-O-feruloyl-beta-D
      glucopyranoside, 4-hydroxyacetophenone 4-O-[5-O-(3,5-dimethoxy-4-hydroxybenzoyl)
      beta-D-apiofrunosyl]-(1-->2)-beta-D-glucopyranoside and 1-O-[2-hydroxy-5-(2
      hydroxyethyl)phenyl]-6-O-trans-caffeoyl-beta-D-glucopyranoside.

PMID- 11237178
TI  - Recent topics in anti-oxidative factors.
AB  - Lipids and anti-oxidative factors regulate immune functions such as
      immunoglobulin production and chemical mediator release. For example,
      polyunsaturated fatty acids (PUFA) enhance IgE production of isolated rat
      lymphocytes, but not in the presence of alpha-tocopherol. In addition, anti
      oxidative factors such as tea polyphenols and flavonoids exert inhibitory effect
      on chemical mediator release from rat peritoneal exudate cells (PEC). Some of
      these immunoregulatory activities of food components could be expressed in vivo.
      Oral administrations of perilla and fish oils or tea polyphenols led to a
      significant decrease of LTB4 releasing activity of rat PEC, but IgE production
      enhancing activity of PUFA was not expressed in vivo. On the other hand, alpha
      tocopherol feeding enhanced serum IgA level as well as IgA productivity of
      mesenteric lymph node lymphocytes. These results suggest that dietary fats and
      antioxidants are effective for the alleviation of allergic symptom and activation
      of immune functions.

PMID- 11237179
TI  - Antioxidative activities of aroma extracts isolated from natural plants.
AB  - Natural leaves and flowers containing numerous aroma chemicals are widely used in
      aromatherapy since ancient times. In addition to their pleasant smells, aroma
      chemicals might have some beneficial health effects. Aroma extracts, isolated
      from coffee beans, soybeans, and mung beans by steam distillation under mild
      conditions (55 degrees C and 85 mm Hg) were examined for their antioxidative
      activities. The inhibitory effect of these extracts toward hexanal/hexanoic acid
      conversion was measured in the testing solution over prolonged time periods. The
      inhibitory effects of these extracts toward malonaldehyde formation from lipids
      oxidized by Fenton's reagent were also measured. The antioxidative activity of
      these extracts, in particular coffee bean extract, was consistent with that of
      BHT or alpha-tocopherol (vitamin E). Soybeans and mung beans extract contained
      maltol, which inhibits hexanal oxidation significantly. Eugenol, which is one of
      the major constituents of mung bean extract, exhibited potent antioxidative
      activity in an aldehyde/carboxylic acid assay. Antioxidants such as eugenol and
      maltol may play an important role in the pharmaceutical activities of natural
      plant extracts used for aromatherapy.

PMID- 11237180
TI  - Antioxidant factors in plant foods and selected oilseeds.
AB  - The effect of dietary factors on health promotion and disease prevention has been
      an issue of interest since antiquity and has become a subject of renewed research
      activity in recent years. Many of the components involved are antioxidative in
      nature and include phenolic compounds. These phenolics exist in the free,
      esterified, glycosylated and polymeric forms. Scrutiny of the source materials,
      their subsequent extraction under optimized conditions and evaluation of
      activity, followed by fractionation and structure elucidation of active
      components is generally necessary. Meals obtained from oilseeds, such as canola,
      mustard, flax, borage, and evening primrose, after oil extraction, contained a
      variety of antioxidative factors. The antioxidative effect of source materials,
      their extracts or fractions thereof, depended on the seed type, the content and
      chemical nature of their active components.

PMID- 11237181
TI  - Generation of lipid peroxyl radicals from edible oils and their biological
      activities: a need for consideration for anti-radical components and purification
      processing.
AB  - Lipid hydroperoxides (LOOH or oxidized oils) are known as unfavorable food
      components. Molecular details of the fate and mechanisms of LOOH to exert adverse
      effects in vivo are, however, little understood. In the present study, we
      demonstrated that LOOH generated alkylperoxyl radical (LOO*) after reaction with
      various heme compounds such as myoglobin, cytochrome c, hemin, hematin, etc., but
      little formation of other radical species was noticed such as L* or LO*. It was
      also shown that LOO* thus formed exhibits cytotoxicity and caused DNA damages
      including strand breakage and abasic site formation. This highly toxic LOO* is
      effectively scavenged by hot water extracts of vegetable (soup), flavonoids,
      polyphenols as well as tocopherols. Another important finding is that crude
      vegetable oils are rich in potent-LOO* scavenging activity, which exhibits potent
      anti-oxidant activity as well; whereas highly purified oils are scanty in such
      components and LOO* scavenging activity. These findings imply that a considerate
      processing in the refining of oils should be needed to retain such potent
      endogenous anti-oxidative radical scavenging-components.

PMID- 11237182
TI  - The JaICA-genox oxidative stress profile--an overview on the profiling technique
      in the oxidative stress assessment and management.
AB  - It is widely accepted that oxidative stress (OS) is a major causative factor for
      many of the age-related dysfunctions and specific diseases. Since the oxidative
      stress state (OSS) of an individual depends on hereditary, dietary, and
      environmental factors, there is a large heterogeneity in the population that may
      be related to disease incidence and longevity. Hence there is a need to assess
      how well an individual is coping against OS. The Japan Institute for the Control
      of Aging (JaICA) and Genox have jointly developed a profiling technique to
      measure the "Oxidative Stress Profiles (JaICA-Genox OSP)" of individuals and
      laboratory test animals. The JaICA-Genox OSP consists of about 45 different
      assays measuring the levels of oxidative damage in lipids and nucleic acids, and
      the antioxidant defenses in the serum. In addition, several bio-markers for
      cardiovascular disease risk are also measured, and assays to measure specific age
      and sex-related hormones in the serum and urine, and race elements in serum,
      urine, and drinking water are also undertaken. This overview discusses the
      designing of the JaICA-Genox OSP and its application in the testing of human
      subjects.

PMID- 11237183
TI  - Cognitive impairment and oxidative stress in the elderly: results of
      epidemiological studies.
AB  - Cognitive impairment is a major component of age-related dementing diseases and
      it has been suggested that it could share the same pathological pathways with
      neurodegenerative processes and cerebrovascular lesions. The free radical theory
      of ageing could be one of these pathways. Implication of free radical damage in
      processes related to cerebral ageing is a good argument in favour of the
      hypothesis that antioxidants may protect against cognitive impairment.
      Observational studies (mostly cross-sectional) of relationships between cognitive
      impairment and antioxidant status are based on the evaluation of dietary intake
      or on the levels of carotenoids, selenium and vitamins A, C and E in plasma or
      red blood cells. More convincing results were obtained on vitamin C and
      carotenoids. Despite some limitations, the comparison between results obtained in
      various populations is becoming increasingly informative and these studies argue
      for a protective effect of antioxidants on cognitive performance.

PMID- 11237184
TI  - Citrus limonoids obacunone and limonin inhibit azoxymethane-induced colon
      carcinogenesis in rats.
AB  - Obacunone and limonin are bitter limonoids in citrus. Their modifying effects on
      the development of aberrant crypt foci (ACF), the activity of detoxification
      enzymes, glutathione S-transferase (GST) and quinone reductase (QR), and cell
      proliferation activity were investigated in male F344 rats treated with
      azoxymethane (AOM). Obacunone and limonin were administered in the diet, during
      the initiation (for 4 weeks) or postinitiation phase (for 4 weeks) of AOM-induced
      tumorigenesis. Feeding of obacunone and limonin (0.02% or 0.05%) caused
      significant reduction (55-65% by "initiation" feeding and 28-42% by
      "postinitiation" feeding) in the yield of ACF. The ability to reduce the
      proliferating cell nuclear antigen-labeling index in crypts and correlated well
      with the prevention of ACF. In a subsequent long-term experiment (38 weeks), in
      which rats were initiated with AOM and fed 0.05% obacunone or 0.05% limonin
      during the initiation or post-initiation phase, both compounds in diet caused
      significant reduction (65%-92% inhibition) in the incidence of colonic
      adenocarcinoma. Thus, citrus bitter limonoids obacunone and limonin possess
      chemopreventive effects on chemically induced rat colon carcinogenesis.

PMID- 11237185
TI  - The role of triterpenoid on reactive oxygen scavenging system: approach from the
      new chemiluminescence system (XYZ system).
AB  - We propose that the reactive oxygen species/hydrogen donor/mediator system (XYZ
      system) is a new chemiluminescence system for the measurement of reactive oxygen
      scavenging activity. By using this method, we demonstrated the role of
      triterpenoid on a reactive oxygen scavenging system. DDMP (2,3-dihydro-2,5
      dihydroxy-6-methyl-4H-pyran-4-one) conjugated saponin from soybean, produced a
      low level light emission in the presence of H202 (X) and gallic acid (Y). The
      soybean saponin acted as a mediator (Z) on the reactive oxygen scavenging system.
      When comparing the data of photon emission properties of saponin with that of
      cholic acids, it concludes that DDMP moiety of soybean saponin plays an important
      role rather than the aglycon moiety in the radical scavenging system.

PMID- 11237186
TI  - Anti-tumor and anti-carcinogenic activities of triterpenoid, beta-boswellic acid.
AB  - Boswellin (BE), a methanol extract of the gum resin exudate of Boswellia serrata,
      contains naturally occurring triterpenoids, beta-boswellic acid and its
      structural related derivatives, has been used as a traditional medicine for the
      treatment of inflammatory and arthritic diseases. Topical application of BE to
      the backs of mice markedly inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)
      induced increases in skin inflammation, epidermal proliferation, the number of
      epidermal cell layers, and tumor promotion in 7,12-dimethylbenz[a]anthracene
      (DMBA)-initiated mice. Feeding 0.2% of BE in the diet to CF-1 mice for 10-24
      weeks reduced the accumulation of parametrial fat pad weight under the abdomen,
      and inhibited azoxymethane (AOM)-induced formation of aberrant crypt foci (ACF)
      by 46%. Addition of pure beta-boswellic acid, 3-O-acetyl-beta-boswellic acid, 11
      keto-beta-boswellic acid or 3-O-acetyl-11-keto-beta-boswellic acid to human
      leukemia HL-60 cell culture inhibited DNA synthesis in HL-60 cells in a dose
      dependent manner with IC50 values ranging from 0.6 to 7.1 microM. These results
      indicate that beta-boswellic acid and its derivatives (the major constituents of
      Boswellin) have anti-carcinogenic, anti-tumor, and anti-hyperlipidemic
      activities.

PMID- 11237187
TI  - Antidiabetogenic activity of oleanolic acid glycosides from medicinal foodstuffs.
AB  - Oleanolic acid glycosides from several medicinal foodstuffs were found to show
      potent inhibitory activity on the increase of serum glucose levels in oral
      glucose-loaded rats. By examination of the structure-activity relationships, the
      3-O-glucuronide moiety and the 28-carboxyl group in oleanolic acid glycosides
      were required to exert the hypoglycemic activity. Oleanolic acid glycosides were
      found to have neither insulin-like nor insulin-releasing activity, but they
      inhibited gastric emptying and glucose-uptake in the small intestine.
      Investigation of the mode of action revealed that the inhibition of gastric
      emptying was mediated by capsaicin-sensitive sensory nerves and the central
      nervous system. Furthermore, oleanolic acid glycosides were suggested to suppress
      the gastric emptying by stimulating the release and/or production of dopamine to
      act through dopamine2 receptors, which in turn causes the release of
      prostaglandins.

PMID- 11237188
TI  - The determination of metabolites of garlic preparations in breath and human
      plasma.
AB  - Gas Chromatography-Mass Spectrometry (GC-MS) was the major technique used to
      determine various metabolites after consumption of dehydrated granular garlic and
      an enteric-coated garlic preparation, in breath, plasma, and simulated gastric
      fluids. A special short-path thermal desorption device was used as an
      introduction technique for the gas chromatograph for the determination of
      volatiles. These garlic preparations release allicin, which decomposes in stomach
      acid or with time in the intestine to release allyl sulfides, disulfides and
      other volatiles, some of which are postulated to be metabolized by glutathione
      and/or S-adenosylmethionine to form allyl methyl sulfide, the main sulfur
      containing volatile metabolite. S-Allylcysteine, a non-volatile bioactive
      component of aged garlic preparations, was determined in human plasma and urine
      by HPLC-MS using the negative ion atmospheric pressure chemical ionization mode
      (APcI)- MS. The technique of selected ion monitoring was used for quantitation. A
      synthetic internal standard of deuterated S-allylcysteine was added to the plasma
      or urine to ensure recovery and to obtain reliable quantitative data.

PMID- 11237189
TI  - Role of dietary lipids in arteriosclerosis in experimental animals.
AB  - Effects of dietary fats include the development of arteriosclerosis in humans and
      experimental animals, in addition to hypercholesterolemia. None of the preceding
      studies explicitly compared the effects of individual fatty acids. To address
      these issues, we chose exogenously hypercholesterolemic (ExHC) rats and
      apolipoprotein (apo) E deficient mice as a model for atherosclerosis and assessed
      the individual role of fatty acids in animals' susceptibility to atherosclerosis.
      The rats fed on the diet containing DHA or EPA, compared with those fed on the
      safflower oil (SO) diet, lowered serum cholesterol concentration, prevented
      platelet aggregation and slowed thickening in the ascending aorta. Apo E
      deficient mice developed hypercholesterolemia and severe lesion area in aortic
      root and arch, to a similar extent when they received DHA or SO. These results
      suggest a direct action of polyunsaturated fatty acids in the arterial wall, in
      addition to their effects on hypocholesterolemic and haemodynamic action.

PMID- 11237190
TI  - Antithrombotic and antineoplastic effects of phyto-organosulfur compounds.
AB  - The antiplatelet activity of methyl allyltrisulfide (MATS), a component commonly
      present in steam-distilled garlic oil, has been demonstrated by the authors. MATS
      inhibits arachidonic acid cascade at the reaction site with PGH synthase.
      However, this enzyme catalyzes two successive reactions, from arachidonic acid to
      PGG2, and from PGG2 to PGH2. The present study revealed that MATS inhibited the
      latter reaction. In addition, our recent findings that to a promyelocytic
      leukemia cell HL60, Allium oils shows marked anti-neoplastic effects representing
      both growth suppression and differentiation activities are described. The garlic
      oil and onion oil showed almost equal ability in inducing the proliferation,
      which measured either by nitroblue-tetrazolium reducing activity assay or by flow
      cytometry for detecting CD11b expression. The combination use of one of these
      oils with all-trans retinoic acid or with dimethyl sulfoxide lead to the marked
      differentiation of the cells, and their effects were estimated to be synergistic.

PMID- 11237191
TI  - Thermochemical transformation of sulfur compounds in Japanese domestic Allium,
      Allium victorialis L.
AB  - Sulfur compounds contributed to the health promotion in Allium species are
      produced via enzymic and thermal reactions. Potent antithrombotic agents which
      have been identified as allyl trisulfides, dithiins, and ajoene in garlic (A.
      sativum) and caucas (A. victorialis) are thermochemically transformed from
      allicin (allyl 2-propenethiosulfinate). The leaves and stems of Japanese domestic
      Allium plant, A. victorialis L. which is widely distributed in the northern part
      of Japan, under the name "Gyoja-ninniku" is a nutritious vegetable. The
      significant flavor compounds of caucas are methyl allyl disulfide (Chinese chive
      odor), diallyl disulfide (garlic-like odor), and dimethyl disulfide and methyl
      allyl trisulfide (pickles-like odor) among more than 85 peaks on the gas
      chromatogram. 2-Vinyl-4H-1,3-dithiin and 3,4-dihydro-3-vinyl-1,2-dithiin as
      platelet aggregation inhibitors were found eliminated in dichloromethane extract
      of caucas. The significant health promoting factors, allyl trisulfides and
      dithiins were relatively increased when caucas was cooked on a frying pan.

PMID- 11237192
TI  - Functional properties of wasabi and horseradish.
AB  - Wasabi (Wasabi japonica) and horseradish (Cholearia arnoracia) are used as spices
      of daily foodstuffs. Allylisothiocyanate (AIT) is a potent component in both
      plants and occurs by grating them. It is well known that AIT shows inhibitory
      effect on the growth of food poisoning bacteria and fungi. In this work, several
      functional properties of roots and leaves from wasabi and horseradish were
      examined in vitro. Each sample showed peroxidase activity. They also exhibited
      antioxidative and superoxide scavenging potency. Antimutagenic activity was
      observed toward 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline [MeIQx], a well
      known mutagen/carcinogen in broiled fish and meat. They also decreased His+
      revertant colonies of 3-chloro-4-dichloromethyl-5-hydroxy-2(5H)-furanone (MX) in
      the Ames test, a strong mutagen and carcinogen in chlorine disinfected tap water.
      Isolation of antimutagenic components in wasabi root was done. Three components
      including (-)-(R)-7-methylsulfinylheptyl isothiocyanate were identified. These
      data show that wasabi and horseradish might be potent functional foods for
      keeping human health.

PMID- 11237193
TI  - Antiplatelet and anticancer isothiocyanates in Japanese domestic horseradish,
      wasabi.
AB  - 6-Methylsulfinylhexyl isothiocyanate (MS-ITC) was isolated from wasabi (Wasabia
      japonica, Japanese domestic horseradish) as a potential inhibitor of human
      platelet aggregation in vitro through our extensive screening of vegetables and
      fruits. In the course of another screening for the induction of glutathione S
      transferase (GST) activity in RL34 cells. MS-ITC was inadvertently isolated from
      wasabi as a potential inducer of GST. MS-ITC administered to rats or mice also
      showed both activities in vivo. As a result from elucidation of the platelet
      aggregation inhibition and the GST induction mechanisms of MS-ITC, the
      isothiocyanate moiety of MS-ITC plays an important role for antiplatelet and
      anticancer activities because of its highly reactivity with sulfhydryl (-SH)
      groups in biomolecules (GSH, cysteine residue in a certain protein, etc.).

PMID- 11237195
TI  - Platelet-activating factor (PAF)-like oxidized phospholipids: relevance to
      atherosclerosis.
AB  - Lipid peroxidation is involved in the pathogenesis of chronic diseases including
      atherosclerosis. Oxidized lipoprotein has diverse biological activities and is
      believed to initiate atheroma formation and maturate fatty plaque. The active
      components of oxidized lipoproteins still remain to be clarified, but a likely
      candidate is the phosphatidylcholine (PC) having an sn-2-short-chain acyl group
      with a methyl, hydroxyl, aldehydic or carboxylic terminal. These unique PCs,
      formed by oxidative fragmentation of the polyunsaturated acyl group of the parent
      PC in liposomes, low density lipoproteins and blood plasma, induce platelet
      aggregation through the activation of the receptor for platelet-activating factor
      (PAF), due to their resemblance in structure with PAF. We have found that PAF
      like lipids regulate DNA synthesis and production of nitric oxide independently
      of the activation of the PAF receptor in vascular smooth muscle cells. Regulation
      of vascular cell function through two distinct signaling pathways mediated by PAF
      like lipids provides new insight into the mechanism of induction of
      atherosclerosis.

PMID- 11237194
TI  - Inhibitory effects of vitamin E on endothelial-dependent adhesive interactions
      with leukocytes induced by oxidized low density lipoprotein.
AB  - Leukocyte-endothelial cell interactions, which are mediated by various adhesion
      molecules, are a crucial event in inflammatory reactions including
      atherosclerosis. Alpha-tocopherol (alpha-Toc) has been used for protection and
      therapy of vascular diseases because of its antioxidant activity. The objective
      of the present study was to determine effect of alpha-Toc on endothelial
      dependent adhesive interactions with leukocytes elicited by oxidized low density
      lipoprotein (oxLDL). Incubation of HUVEC with oxLDL (100 microg/mL) increased
      expression of proteins and messenger RNA of intercellular adhesion molecule-1
      (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on enzyme immunoassay and
      northern blotting assay; pretreatment with alpha-Toc reduced in a dose dependent
      manner. Adherence of polymorphonuclear leukocytes (PMN) or mononuclear leukocytes
      (MNC) to oxLDL-activated HUVEC was much increased compared with that to
      unstimulated HUVEC. Treatment of HUVEC with alpha-Toc, monoclonal antibody to
      ICAM-1 or VCAM-1 inhibited adherence of PMN or MNC in a dose dependent manner.
      These results suggest that alpha-Toc works as anti-atherogenic agent through
      inhibiting endothelial-dependent adhesive interactions with leukocytes induced by
      oxLDL.

PMID- 11237196
TI  - Relationship between fatty acids and the endocrine system.
AB  - Significant interactions exist between fatty acids and the endocrine system.
      Hormones affect the metabolism of fatty acids and the fatty acid composition of
      tissue lipids. The principal hormones involved in lipid metabolism are insulin,
      glucagon, catecholamines, cortisol and growth hormone. The concentrations of
      these hormones are altered in chronic degenerative conditions such as diabetes
      and cardiovascular disease, which in turn lead to alterations in tissue lipids.
      Lipogenesis and lipolysis, which modulate fatty acid concentrations in plasma and
      tissues, are under hormonal control. Neuropeptides are involved in lipid
      metabolism in brain and other tissues. Polyunsaturated fatty acids (PUFA) are
      also precursors for eicosanoids including prostaglandins, leukotrienes, and
      thromboxanes, which have hormone-like activities. Fatty acids in turn alter both
      hormone and neuropeptide concentrations and their receptors. Saturated and trans
      fatty acids (TFA) decrease insulin concentration leading to insulin resistance.
      In contrast, PUFA increase plasma insulin concentration and decrease insulin
      resistance. In humans, omega-3 PUFA alter the levels of opioid peptides in
      plasma.

PMID- 11237198
TI  - Preventive effects of drinking green tea on cancer and cardiovascular disease:
      epidemiological evidence for multiple targeting prevention.
AB  - The significance of drinking green tea in prevention of two of the main lifestyle
      related diseases, cancer and cardiovascular disease, was demonstrated in terms of
      a prospective cohort study on a total of 8,552 general residents in Saitama
      Prefecture, Japan. On the basis of the follow-up study, we revealed decreased
      relative risk of cancer incidence for those consuming over 10 cups a day,
      compared with those consuming below 3 cups: 0.54 (95% confidence interval, 0.22
      1.34) for men, 0.57 (0.34-0.98) for women, and 0.59 (0.35-0.98) for both sexes.
      Furthermore, a significant delay in cancer onset was associated with increased
      consumption of green tea. Next, decreased relative risk of death from
      cardiovascular disease was 0.58 (0.34-0.99) for men, 0.82 (0.49-1.38) for women,
      and 0.72 (0.60-1.04) for members of both sexes consuming over 10 cups a day.
      Finally, we evaluated the life-prolonging effects of drinking green tea on
      cumulative survival, using the life table.

PMID- 11237197
TI  - Anti-stress effects of DHA.
AB  - DHA is abundant in the brain. Deficiency of DHA changes behavior in animals. The
      purpose of the present studies was to clarify the effect of DHA intake on
      hostility and plasma catecholamines. In study 1, forty-one students took either
      DHA-rich oil capsules containing 1.5-1.8 g DHA/d (17 females and 5 males) or
      control oil capsules containing 97% soybean oil plus 3% fish oil (12 females and
      7 males) for 3 mon in a double blind fashion. They took a psychological test (P-F
      Study) at the start and end of the study. Study I started at the end of summer
      vacation and ended in the middle of mental stress of final exams. In the control
      group, hostility measured by P-F Study was significantly increased at the end of
      the study as compared with that measured at the start (+58%), whereas it was not
      significantly changed in the DHA group (-14%). In a similar double blind two-mon
      study (study 2), we measured plasma catecholamines and cortisol of students (3
      females and 4 males for the DHA group and the same numbers for the control) at
      the start and end of the study. In study 2 the students were under a continuous
      stress of final exams that lasted for two mon throughout the whole study period.
      The plasma cortisol did not change in either group, but the norepinephrine
      concentration was significantly decreased in the DHA group (-31%), whereas it
      stayed at the same level in the control group. These effects of DHA intake may be
      applied to people under psychological stress.

PMID- 11237199
TI  - Metabolic effects of omega-3 fatty acids.
AB  - Some metabolic effects of dietary marine oils, or of dietary eicosapentaenoic or
      docosahexaenoic acid are reviewed. It is pointed out that docosahexaenoic acid
      appears more effective as regards induction of peroxisomal beta-oxidation.
      Similarly, docosahexaenoic appears more powerful in terms of suppression of
      hepatic delta9-desaturase activity and mRNA-levels. The potential inhibitory
      effect of polyunsaturated fatty acids, particularly docosahexaenoic acid, on
      mitochondrial beta-oxidation is discussed. Experiments with rats suggesting that
      the hypolipidaemic response of eicosapentaenoic acid is more marked when the
      fatty acid was given to fed rats, as compared to fasted rats, are discussed.

PMID- 11237200
TI  - Absorption, metabolism and antioxidative effects of tea catechin in humans.
AB  - Green tea is consumed as a popular beverage in Japan and throughout the world.
      During the past decade, epidemiological studies have shown that tea catechin
      intake is associated with lower risk of cardiovascular disease. In vitro
      biochemical studies have reported that catechins, particularly epigallocatechin-3
      gallate (EGCg), help to prevent oxidation of plasma low-density lipoprotein
      (LDL). LDL oxidation has been recognized to be an important step in the formation
      of atherosclerotic plaques and subsequent cardiovascular disease. Metabolic
      studies have shown that EGCg supplement is incorporated into human plasma at a
      maximum concentration of 4400 pmol/mL. Such concentrations would be enough to
      exert antioxidative activity in the blood stream. The potent antioxidant property
      of tea catechin may be beneficial in preventing the oxidation of LDL. It is of
      interest to examine the effect of green tea catechin supplementation on
      antioxidant capacity of plasma in humans by measuring plasma phosphatidylcholine
      hydroperoxide (PCOOH) as a marker of oxidized lipoproteins.

PMID- 11237201
TI  - Regulation of intestinal glucose transport by tea catechins.
AB  - Intestinal glucose uptake is mainly performed by its specific transporters, such
      as SGLT 1, GLUT 2 and 5 expressed in the intestinal epithelial cells. By using
      human intestinal epithelial Caco-2 cells we observed that intestinal glucose
      uptake was markedly inhibited by tea extracts. While several substances in green
      tea seem to be involved in this inhibition, catechins play the major role and
      epicatechin gallate (ECg) showed the highest inhibitory activity. Since our Caco
      2 cells did not express enough amount of SGLT 1, the most abundant intestinal
      glucose transporter, the effect of ECg on SGLT 1 was evaluated by using brush
      border membrane vesicles obtained from the rabbit small intestine. ECg inhibited
      SGLT 1 in a competitive manner, although ECg itself was not transported via the
      glucose transporters. These results suggest that tea catechins could play a role
      in controlling the dietary glucose uptake at the intestinal tract and possibly
      contribute to blood glucose homeostasis.

PMID- 11237202
TI  - Mechanisms of cancer prevention by tea polyphenols based on inhibition of TNF
      alpha expression.
AB  - Among various biochemical and biological activities of tea polyphenols, we
      believe inhibition of the expression and release of tumor necrosis factor-alpha
      (TNF-alpha) is crucial, since our study with TNF-alpha-deficient mice has
      revealed that TNF-alpha is an essential factor in tumor promotion. We found that
      EGCG dose-dependently inhibited AP-1 and NF-kappaB activation in BALB/3T3 cells
      treated with okadaic acid, resulting in inhibition of TNF-alpha gene expression.
      Furthermore, treatment with 0.1% green tea extract in drinking water reduced TNF
      alpha gene expression as well as TNF-alpha protein level in the lung of TNF-alpha
      transgenic mice; and IL-1beta and IL-10 gene expression in the lung was also
      inhibited by treatment with green tea extract, indicating that green tea inhibits
      both TNF-alpha and the cytokines induced by TNF-alpha in organs. We recently
      found synergistic effects of EGCG and cancer preventive agents such as tamoxifen
      and sulindac, on cancer preventive activity. Taken together, the results show
      that green tea is efficacious as a non-toxic cancer preventive for humans.

PMID- 11237203
TI  - Mechanisms of inhibition of carcinogenesis by tea.
AB  - Tea (Camellia sinensis) preparations have been shown to inhibit tumorigenesis at
      the initiation, promotion, and progression stages in different animal models. The
      anti-proliferative effects of tea polyphenols may be a key mechanism, especially
      in the NNK-induced lung tumorigenesis model with mice. Studies with cell lines
      have demonstrated that tea polyphenols inhibit cell proliferation and induce
      apoptosis. The effective concentrations used in these studies (20-100 microM) are
      usually higher than those observed in blood and tissues of humans and animals,
      which are in the low micromolar range. Glucuronide and sulfate conjugated and
      methylated catechins as well as ring fission products (due to intestinal
      microflora) have been observed in human plasma and urine. Purified green and
      black tea polyphenols inhibited the H-ras induced milogen-activated protein
      kinases, AP-1 activities, and the growth of 30.7b Ras 12 and BES21 cells. Among
      the catechins, both the galloyl structure on the B ring and the gallate moiety
      are important for the inhibition. Both (-)-epigallocatechin-3-gallate and
      theaflavin-3,3'-digallate inhibited the phosphorylation of c-jun and p44/42 (ERK
      1/2). More mechanistic and human studies in these areas will help us to
      understand the possible inhibitory action of tea against carcinogenesis in
      humans.

PMID- 11237204
TI  - Tea catechins and related polyphenols as anti-cancer agents.
AB  - Epigallocatechin gallate (EGCg) and theaflavins, a major constituent of green tea
      infusion and the constituents of black tea, respectively, were found to inhibit
      matrix metalloproteinases (MMPs) which are intimately associated with tumor
      invasion and metastasis. EGCg and related polyphenols exhibited apoptosis
      inducing activity for several cancer cell lines including human stomach and colon
      cancer cells. Comparison of the activity of these compounds revealed the
      importance of the number and the steric disposition of hydroxyl groups. A
      pyrogallol-type structure in a molecule is a minimum requirement for apoptosis
      induction of catechin compounds and that in the B ring has an important role in
      the activity. These data would provide useful information for designing anti
      cancer agents on the basis of anti-inhibitory activity for MMPs and/or apoptosis
      inducing activity.

PMID- 11237205
TI  - Cancer prevention by natural carotenoids.
AB  - Various natural carotenoids were proven to have anticarcinogenic activity.
      Epidemiological investigations have shown that cancer risk is inversely related
      to the consumption of green and yellow vegetables and fruits. Since beta-carotene
      is present in abundance in these vegetables and fruits, it has been investigated
      extensively as possible cancer preventive agent. However, various carotenoids
      which co-exist with beta-carotene in vegetables and fruits also have anti
      carcinogenic activity. And some of them, such as alpha-carotene, showed higher
      potency than beta-carotene to suppress experimental carcinogenesis. Thus, we have
      carried out more extensive studies on cancer preventive activities of natural
      carotenoids in foods; i.e., lutein, lycopene, zeaxanthin and beta-cryptoxanthin.
      Analysis of the action mechanism of these natural carotenoids is now in progress,
      and some interesting results have already obtained; for example, beta
      cryptoxanthin was suggested to stimulate the expression of RB gene, an anti
      oncogene, and p73 gene, which is known as one of the p53-related genes. Based on
      these results, multi-carotenoids (mixture of natural carotenoids) seems to be of
      interest to evaluate its usefulness for practice in human cancer prevention.

PMID- 11237206
TI  - Effect of dietary alpha-linolenic acid on the activity and gene expression of
      hepatic fatty acid oxidation enzymes.
AB  - The activities of hepatic fatty acid oxidation enzymes in rats fed linseed and
      perilla oils rich in alpha-linolenic acid (alpha-18:3) were compared with those
      in the animals fed safflower oil rich in linoleic acid (18:2) and saturated fats
      (coconut or palm oil). Mitochondrial and peroxisomal palmitoyl-CoA (16:0-CoA)
      oxidation rates in the liver homogenates were significantly higher in rats fed
      linseed and perilla oils than in those fed saturated fats and safflower oil. The
      fatty oxidation rates increased as dietary levels of alpha-18:3 increased.
      Dietary alpha-18:3 also increased the activity of fatty acid oxidation enzymes
      except for 3-hydroxyacyl-CoA dehydrogenase. Unexpectedly, dietary alpha-18:3
      caused great reduction in the activity of 3-hydroxyacyl-CoA dehydrogenase
      measured with short- and medium-chain substrates but not with long-chain
      substrate. Dietary alpha-18:3 significantly increased the mRNA levels of hepatic
      fatty acid oxidation enzymes including carnitine palmitoyltransferase I and II,
      mitochondrial trifunctional protein, acyl-CoA oxidase, peroxisomal bifunctional
      protein, mitochondrial and peroxisomal 3-ketoacyl-CoA thiolases, 2, 4-dienoyl-CoA
      reductase and delta3, delta2-enoyl-CoA isomerase. Fish oil rich in very long
      chain n-3 fatty acids caused similar changes in hepatic fatty acid oxidation.
      Regarding the substrate specificity of beta-oxidation pathway, mitochondrial and
      peroxisomal beta-oxidation rate of alpha-18:3-CoA, relative to 16:0- and 18:2
      CoAs, was higher irrespective of the substrate/albumin ratios in the assay
      mixture or dietary fat sources. The substrate specificity of carnitine
      palmitoyltransferase I appeared to be responsible for the differential
      mitochondrial oxidation rates of these acyl-CoA substrates. Dietary fats rich in
      alpha-18:3-CoA relative to safflower oil did not affect the hepatic activity of
      fatty acid synthase and glucose 6-phosphate dehydrogenase. It was suggested that
      both substrate specificities and alterations in the activities of the enzymes in
      beta-oxidation pathway play a significant role in the regulation of the serum
      lipid concentrations in rats fed alpha-18:3.

PMID- 11237207
TI  - Chemoprevention of lung cancer by lycopene.
AB  - An investigation was conducted to assess the chemopreventive potential of
      lycopene (LP), a naturally occurring hydrocarbon carotenoid found in tomatoes and
      their products, administered during the post-initiation stage in a multiorgan
      carcinogenesis model. One hundred eighteen B6C3F1 mice of both sexes were
      subjected to combined treatment with diethylnitrosamine (DEN), N-methyl-N
      nitrosourea (MNU) and 1,2-dimethylhydrazine (DMH) from day 11 after birth to week
      9 (DMD treatment) (groups 1 and 2) or given their vehicles (group 3). Then group
      1 received LP (25 or 50 ppm in drinking water) for 21 weeks from weeks 11 to 32.
      Group 2 served as a carcinogen alone control and group 3 was given only LP (25 or
      50 ppm). The incidences and multiplicities of lung adenomas plus carcinomas
      combined in male mice in group 1 receiving LP 50 ppm were significantly decreased
      as compared to the DMD alone or DMD and LP 25 ppm group values (75.0 vs 18.8%, P
      < 0.02; 0.94+/-0.17 v.s 0.25+/-0.14, P < 0.001). While hepatocellular carcinomas
      were lacking in the DMD and LP groups, two cases were found in the DMD alone
      group (not statistically significant). The values for aberrant crypt foci (ACF)
      and tumors in the colon and kidney did not show any significant variation among
      the carcinogen-treated subgroups. The results of this study provide evidence that
      the tomato carotenoid, lycopene, may have potential as a chemopreventive agent
      against carcinogenesis in the male lung.

PMID- 11237208
TI  - Protein glycation, diabetes, and aging.
AB  - Biological amines react with reducing sugars to form a complex family of
      rearranged and dehydrated covalent adducts that are often yellow-brown and/or
      fluorescent and include many cross-linked structures. Food chemists have long
      studied this process as a source of flavor, color, and texture changes in cooked,
      processed, and stored foods. During the 1970s and 1980s, it was realized that
      this process, called the Maillard reaction or advanced glycation, also occurs
      slowly in vivo. Advanced glycation endproducts (AGEs) that form are implicated,
      causing the complications of diabetes and aging, primarily via adventitious and
      crosslinking of proteins. Long-lived proteins such as structural collagen and
      lens crystallins particularly are implicated as pathogenic targets of AGE
      processes. AGE formation in vascular wall collagen appears to be an especially
      deleterious event, causing crosslinking of collagen molecules to each other and
      to circulating proteins. This leads to plaque formation, basement membrane
      thickening, and loss of vascular elasticity. The chemistry of these later-stage,
      glycation-derived crosslinks is still incompletely understood but, based on the
      hypothesis that AGE formation involves reactive carbonyl groups, the authors
      introduced the carbonyl reagent aminoguanidine hydrochloride as an inhibitor of
      AGE formation in vivo in the mid 1980s. Subsequent studies by many researchers
      have shown the effectiveness of aminoguanidine in slowing or preventing a wide
      range of complications of diabetes and aging in animals and, recently, in humans.
      Since, the authors have developed a new class of agents, exemplified by 4,5
      dimethyl-3-phenacylthiazolium chloride (DPTC), which can chemically break already
      formed AGE protein-protein crosslinks. These agents are based on a new theory of
      AGE crosslinking that postulates that alpha-dicarbonyl structures are present in
      AGE protein-protein crosslinks. In studies in aged animals, DPTC has been shown
      to be capable of reverting indices of vascular compliance to levels seen in
      younger animals. Human clinical trials are underway.

PMID- 11237210
TI  - Ras activation of the Raf kinase: tyrosine kinase recruitment of the MAP kinase
      cascade.
AB  - A continuing focus of our work has been an effort to understand the signal
      transduction pathways through which insulin achieves its cellular actions. In the
      mid-1970s, we and others observed that insulin promoted an increase in Ser/Thr
      phosphorylation of a subset of cellular proteins. This finding was unanticipated,
      inasmuch as nearly all of the actions of insulin then known appeared to result
      from protein dephosphorylation. In fact, nearly 15 years elapsed before any
      physiologic response to insulin attributable to stimulated (Ser/Thr)
      phosphorylation was established. Nevertheless, based on the hypothesis that
      insulin-stimulated Ser/Thr phosphorylation reflected the activation of protein
      (Ser/Thr) kinases downstream of the insulin receptor, we sought to detect and
      purify these putative, insulin-responsive protein (Ser/Thr) kinases. Our effort
      was based on the presumption that an understanding of the mechanism for their
      activation would provide an entry into the biochemical reactions through which
      the insulin receptor activated its downstream effectors. To a degree that, in
      retrospect, is surprising, this goal was accomplished, much in the way originally
      envisioned. It is now well known that receptor tyrosine kinases (RTKs) recruit a
      large network of protein (Ser/Thr) kinases to execute their cellular programs.
      The first of these insulin-activated protein kinase networks to be fully
      elucidated was the Ras-Raf-mitogen-activated protein kinase (MAPK) cascade. This
      pathway is a central effector of cellular differentiation in development;
      moreover, its inappropriate and continuous activation provides a potent
      promitogenic force and is a very common occurrence in human cancers. Conversely,
      this pathway contributes minimally, if at all, to insulin's program of metabolic
      regulation. Nevertheless, the importance of the Ras-MAPK pathway in metazoan
      biology and human malignancies has impelled us to an ongoing analysis of the
      functions and regulation of Ras and Raf. This chapter will summarize briefly the
      way in which work from this and other laboratories on insulin signaling led to
      the discovery of the mammalian MAP kinase cascade and, in turn, to the
      identification of unique role of the Raf kinases in RTK activation of this
      protein (Ser/Thr) kinase cascade. We will then review in more detail current
      understanding of the biochemical mechanism through which the Ras proto-oncogene,
      in collaboration with the 14-3-3 protein and other protein kinases, initiates
      activation of the Raf kinase.

PMID- 11237209
TI  - Discovery of a small molecule insulin receptor activator.
AB  - Insulin elicits diverse biological responses in many tissues and cell types by
      binding to its specific receptor. The insulin receptor (IR) is a tetramer
      consisting of two extracellular alpha subunits and two membrane-spanning beta
      subunits. The binding of insulin to the receptor causes conformational changes
      that lead to autophosphorylation and activation of the tyrosine kinase intrinsic
      to the beta subunits. Insulin receptor transphosphorylates several immediate
      substrates, resulting in modulation of a cascade of downstream signal
      transduction molecules. In order to discover small molecules that activate the
      human insulin receptor tyrosine kinase (IRTK), a cell-based assay was established
      and utilized to screen a collection of synthetic chemicals and natural product
      extracts. This effort led to the identification of a nonpeptidyl, small molecule,
      insulin-mimetic compound (demethylasterriquinone B-1, DMAQ-B1) that was isolated
      from a mixture of metabolites produced by a tropical endophytic fungus,
      Pseudomassaria sp. This compound induced human IRTK activation and increased
      tyrosine phosphorylation of IR beta subunit. It mediated insulin-like effects,
      including insulin receptor substrate-1 (IRS-1) phosphorylation and activation of
      phosphotidylinositide 3-kinase and Akt kinase. DMAQ-B1 also exhibited an insulin
      like effect on glucose uptake in adipocytes and skeletal muscle tissue.
      Furthermore, the compound was relatively selective for IR vs. insulin-like growth
      factor-I (IGF-I) receptor and other homologous receptor tyrosine kinases. In
      addition, it activated partially purified native IR or recombinant IR kinase,
      demonstrating the direct interaction of the small molecule with the IR. Oral
      administration of DMAQ-B1 resulted in significant glucose lowering in two mouse
      models of diabetes. Thus, DMAQ-B1 represents the first orally active insulin
      mimetic agent. Pharmaceutical intervention aimed at augmenting IR function
      ultimately may prove beneficial as a novel therapeutic option in patients with
      diabetes.

PMID- 11237211
TI  - The role of protein phosphatase-1 in insulin action.
AB  - Insulin is the most-potent physiological anabolic agent known, promoting the
      synthesis and storage of carbohydrates and lipids and inhibiting their
      degradation and release into the circulation. This action of the hormone is due
      in part to the acute regulation of metabolic enzymes through changes in their
      phosphorylation state. In fat, liver, and muscle, insulin stimulates the
      dephosphorylation of a number of enzymes involved in glycogen and lipid
      metabolism via activation of protein phosphatases. Numerous studies have
      indicated that protein phosphatase-1 (PP1) is the primary phosphatase involved in
      insulin action. Although PP1 is a cytosolic protein, the phosphatase is
      compartmentalized in cells by discrete targeting subunits. These proteins confer
      substrate specificity to PP1 and mediate the specific regulation of intracellular
      pools of PP1 by a variety of extracellular signals. Four proteins have been
      described that target the phosphatase to the glycogen particle. G(M) and GL are
      expressed exclusively in striated muscle and liver, while protein targeting to
      glycogen (PTG) and R6 are more widely expressed. Despite a common targeting
      function, these four proteins are not highly conserved, suggesting profound
      differences in the mechanisms by which they contribute to the hormonal regulation
      of PP1 activity. Overexpression studies in cell lines or animals have revealed
      major differences among these proteins regarding basal glycogen levels and
      hormonal responsiveness. Furthermore, alterations in the expression or function
      of PP1 glycogen-targeting subunits may contribute to the onset of insulin
      resistance and type 2 diabetes.

PMID- 11237212
TI  - Intracellular organization of insulin signaling and GLUT4 translocation.
AB  - Glucose is cleared from the bloodstream by a family of facilitative transporters
      (GLUTs), which catalyze the transport of glucose down its concentration gradient
      and into cells of target tissues, primarily striated muscle and adipose.
      Currently, there are five established functional facilitative glucose transporter
      isoforms (GLUT1-4 and GLUTX1), with GLUT5 being a fructose transporter. GLUT1 is
      ubiquitously expressed with particularly high levels in human erythrocytes and in
      the endothelial cells lining the blood vessels of the brain. GLUT3 is expressed
      primarily in neurons and, together, GLUT1 and GLUT3 allow glucose to cross the
      blood-brain barrier and enter neurons. GLUT2 is a low-affinity (high Km) glucose
      transporter present in liver, intestine, kidney, and pancreatic beta cells. This
      transporter functions as part of the glucose sensor system in beta cells and in
      the basolateral transport of intestinal epithelial cells that absorb glucose from
      the diet. A new facilitative glucose transporter protein, GLUTX1, has been
      identified and appears to be important in early blastocyst development. The GLUT4
      isoform is the major insulin-responsive transporter that is predominantly
      restricted to striated muscle and adipose tissue. In contrast to the other GLUT
      isoforms, which are primarily localized to the cell surface membrane, GLUT4
      transporter proteins are sequestered into specialized storage vesicles that
      remain within the cell's interior under basal conditions. As postprandial glucose
      levels rise, the subsequent increase in circulating insulin activates
      intracellular signaling cascades that ultimately result in the translocation of
      the GLUT4 storage compartments to the plasma membrane. Importantly, this process
      is readily reversible such that when circulating insulin levels decline, GLUT4
      transporters are removed from the plasma membrane by endocytosis and are recycled
      back to their intracellular storage compartments. Therefore, by establishing an
      internal membrane compartment as the default localization for the GLUT4
      transporters, insulin-responsive tissues are poised to respond rapidly and
      efficiently to fluctuations in circulating insulin levels. Unfortunately, the
      complexity of these regulatory processes provides numerous potential targets that
      may be defective and eventually result in peripheral tissue insulin resistance
      and possibly diabetes. As such, understanding the molecular details of GLUT4
      expression, GLUT4 vesicle compartment biogenesis, GLUT4 sequestration, vesicle
      trafficking, and fusion with the plasma membrane has become a major focus for
      many laboratories. This chapter will focus on recently elucidated insulin signal
      transduction pathways and GLUT4 vesicle trafficking components that are necessary
      for insulin-stimulated glucose uptake and GLUT4 translocation in adipocytes.

PMID- 11237213
TI  - Cell-specific roles of glucokinase in glucose homeostasis.
AB  - Mutations in the glucokinase (GK) gene cause two different diseases of blood
      glucose regulation: maturity onset diabetes of the young, type 2 (MODY-2) and
      persistent hyperinsulinemic hypoglycemia of infancy (PHHI). To gain further
      understanding of the pathophysiology of these disorders, we have used both
      transgenic and gene-targeting strategies to explore the relationship between GK
      gene expression in specific tissues and the blood glucose concentration. These
      studies, which have included the use of aCre/loxP gene-targeting strategy to
      perform both pancreatic beta-cell- and hepatocyte-specific knockouts of GK,
      clearly demonstrate multiple, cell-specific roles for this hexokinase that,
      together, contribute to the maintainance of euglycemia. In the pancreatic beta
      cell, GK functions as the glucose sensor, determining the threshold for insulin
      secretion. Mice lacking GK in the pancreatic beta cell die within 3 days of birth
      of profound hyperglycemia. In the liver, GK facilitates hepatic glucose uptake
      during hyperglycemia and is essential for the appropriate regulation of a network
      of glucose-responsive genes. While mice lacking hepatic GK are viable, and are
      only mildly hyperglycemic when fasted, they also have impaired insulin secretion
      in response to hyperglycemia. The mechanisms that enable hepatic GK to affect
      beta-cell function are not yet understood. Thus, the hyperglycemia that occurs in
      MODY-2 is due to impaired GK function in both the liver and pancreatic beta cell,
      although the defect in beta-cell function is clearly more dominant. Whether
      defects in GK gene expression also impair glucose sensing by neurons in the brain
      or enteroendocrine cells in gut, two other sites known to express GK, remains to
      be determined. Moreover, whether the pathophysiology of PHHI also involves
      multitissue dysfunction remains to be explored.

PMID- 11237214
TI  - Nuclear magnetic resonance studies of hepatic glucose metabolism in humans.
AB  - Nuclear magnetic resonance (NMR) spectroscopy has made noninvasive and repetitive
      measurements of human hepatic glycogen concentrations possible. Monitoring of
      liver glycogen in real-time mode has demonstrated that glycogen concentrations
      decrease linearly and that net hepatic glycogenolysis contributes only about 50
      percent to glucose production during the early period of a fast. Following a
      mixed meal, hepatic glycogen represents approximately 20 percent of the ingested
      carbohydrates, while only about 10 percent of an intravenous glucose load is
      retained by the liver as glycogen. During mixed-meal ingestion, poorly controlled
      type 1 diabetic patients synthesize only about 30 percent of the glycogen stored
      in livers of nondiabetic humans studied under similar conditions. Reduced net
      glycogen synthesis can be improved but not normalized by short-term, intensified
      insulin treatment. A decreased increment in liver glycogen content following
      meals was also found in patients with maturity-onset diabetes of the young due to
      glucokinase mutations (MODY-2). In patients with poorly controlled type 2
      diabetes, fasting hyperglycemia can be attributed mainly to increased rates of
      endogenous glucose production, which was found by 13C NMR to be due to increased
      rates of gluconeogenesis. Metformin treatment improved fasting hyperglycemia in
      these patients through a reduction in hepatic glucose production, which could be
      attributed to a decrease in gluconeogenesis. In conclusion, NMR spectroscopy has
      provided new insights into the pathogenesis of hyperglycemia in type 1, type 2,
      and MODY diabetes and offers the potential of providing new insights into the
      mechanism of action of novel antidabetic therapies.

PMID- 11237215
TI  - BETA2 and pancreatic islet development.
AB  - The pancreas is essential for digestion and glucose homeostasis. Diseases
      associated with the pancreas (e.g., pancreatitis, pancreatic cancer, diabetes)
      are generally debilitating for the patient. Diabetes is particularly prominent in
      the United States, affecting nearly 6 percent of the population, with associated
      annual health costs in the billions of dollars. Pancreas development is a complex
      process that requires the timely expression of numerous factors. Among them, a
      basic Helix-Loop-Helix factor, BETA2, was shown to be important for terminal
      differentiation of islet cells including insulin- and glucagon-producing cells.
      Expression studies demonstrated the presence of BETA2 in islet cells and specific
      neurons. Targeted deletion of the BETA2 gene in mice revealed its significance in
      pancreas development. In addition, BETA2 is important in granule cell development
      of the hippocampus and cerebellum. This chapter will focus on the role of BETA2
      in pancreas physiology, neuronal development, and its molecular biology.

PMID- 11237216
TI  - Peroxisome proliferator-activated receptors: from genes to physiology.
AB  - The peroxisome proliferator-activated receptors (PPARalpha, gamma, delta) are
      members of the nuclear receptor superfamily of ligand-activated transcription
      factors that have central roles in the storage and catabolism of fatty acids.
      Although the three PPAR subtypes are closely related and bind to similar DNA
      response elements as heterodimers with the 9-cis retinoic acid receptor RXR, each
      subserves a distinct physiology. PPARalpha (NR1C1) is the receptor for the
      fibrate drugs, which are widely used to lower triglycerides and raise high
      density lipoprotein cholesterol levels in the treatment and prevention of
      coronary artery disease. In rodents, PPARalpha agonists induce hepatomegaly and
      stimulate a dramatic proliferation of peroxisomes as part of a coordinated
      physiological response to lipid overload. PPARgamma (NR1C3) plays a critical role
      in adipocyte differentiation and serves as the receptor for the glitazone class
      of insulin-sensitizing drugs used in the treatment of type 2 diabetes. In
      contrast to PPARalpha and PPARgamma, relatively little is known about the biology
      of PPARdelta (NR1C2), although recent findings suggest that this subtype also has
      a role in lipid homeostasis. All three PPARs are activated by naturally occurring
      fatty acids and fatty acid metabolites, indicating that they function as the
      body's fatty acid sensors. Three-dimensional crystal structures reveal that the
      ligand-binding pockets of the PPARs are much larger and more accessible than
      those of other nuclear receptors, providing a molecular basis for the promiscuous
      ligand-binding properties of these receptors. Given the fundamental roles that
      the PPARs play in energy balance, drugs that modulate PPAR activity are likely to
      be useful for treating a wide range of metabolic disorders, including
      atherosclerosis, dyslipidemia, obesity, and type 2 diabetes.

PMID- 11237217
TI  - Insulin resistance and its treatment by thiazolidinediones.
AB  - Insulin resistance is a change in physiologic regulation such that a fixed dose
      of insulin causes less of an effect on glucose metabolism than occurs in normal
      individuals. The normal compensatory response to insulin resistance is an
      increase in insulin secretion that results in hyperinsulinemia. If the
      hyperinsulinemia is sufficient to overcome the insulin resistance, glucose
      regulation remains normal; if not, type 2 diabetes ensues. Associated with
      insulin resistance, however, is a cluster of other metabolic abnormalities
      involving body fat distribution, lipid metabolism, thrombosis and fibrinolysis,
      blood pressure regulation, and endothelial cell function. This cluster of
      abnormalities is referred to as the insulin resistance syndrome or the metabolic
      syndrome. It is causally related not only to the development of type 2 diabetes
      but also to cardiovascular disease. A major unresolved issue is whether there is
      a single underlying cause of this syndrome and, if so, what might it be? Several
      promising hypotheses have been proposed. There are some data to support the
      hypothesis that fetal malnutrition imprints on metabolic regulatory processes
      that, in later adult life, predispose to the development of the insulin
      resistance syndrome. Visceral obesity also has been a candidate for the cause of
      the syndrome. Whatever mechanism is ultimately found to be responsible, it will
      undoubtedly have both genetic and environmental components. Among the biochemical
      mediators that are likely to be responsible for the interference with insulin's
      effects on intermediary metabolism are free fatty acids and other products from
      adipose tissue. Recent data suggest that the substances stimulate serine
      phosphorylation of molecules involved in the initial steps of insulin action,
      thereby blocking the ability of these molecules to be tyrosine phosphorylated and
      initiate the subsequent steps of the insulin action cascade. The
      thiazolidinediones are a new class of agents that have been developed to treat
      type 2 diabetic patients. These drugs act as peroxisome proliferator-activated
      receptor gamma (PPARgamma) agonists. Following their binding to the receptor, the
      heterodimer molecule that contains the binding site is activated. The activated
      complex binds to the response elements of specific genes that regulate molecules
      that effect insulin action and lipid metabolism. These genes are either activated
      or inhibited. Specifically, the thiazolidinediones improve insulin action and
      decrease insulin resistance. The exact mechanism by which these agents decrease
      insulin resistance is not clear but they do decrease the elevated free fatty acid
      levels present in insulin-resistant patients and they appear to change the body
      distribution of adipose tissue. Treatment of insulin-resistant type 2 diabetic
      patients with thiazolidinediones not only improves glycemic control and decreases
      insulin resistance, it also improves many of the abnormalities that are part of
      the insulin resistance syndrome.

PMID- 11237218
TI  - Insulin resistance in polycystic ovary syndrome: progress and paradoxes.
AB  - Over the past 20 years, it has been clearly documented that 1) polycystic ovary
      syndrome (PCOS) has major metabolic sequelae related to insulin resistance and 2)
      insulin resistance plays an important role in the pathogenesis of the
      reproductive abnormalities of the disorder. Women with PCOS are at significantly
      increased risk of developing type 2 diabetes mellitus (DM). Studies in isolated
      adipocytes and in cultured skin fibroblasts from PCOS women have demonstrated
      intrinsic postbinding defects in insulin-mediated glucose metabolism. In
      fibroblasts, the mitogenic pathway of insulin action is intact, consistent with a
      selective defect in insulin signaling. While PCOS skeletal muscle is resistant to
      insulin in vivo, cultured muscle cells have normal insulin sensitivity,
      consistent with a major role of extrinsic factors in producing insulin resistance
      in this tissue. Excessive serine phosphorylation of the insulin receptor or
      downstream signaling proteins may be involved in the pathogenesis of insulin
      resistance in PCOS. The putative serine kinase is extrinsic to the insulin
      receptor but its identity is unknown. The explanations for tissue-specific and
      signaling pathway-specific differences in insulin action in PCOS are unknown but
      may involve differential roles of insulin receptor substrate (IRS)-1 and IRS-2 in
      insulin signal transduction.

PMID- 11237219
TI  - The beta-adrenergic receptors and the control of adipose tissue metabolism and
      thermogenesis.
AB  - The beta-adrenergic receptors (betaARs) are members of the large family of G
      protein-coupled receptors. There are three betaAR subtypes (beta1AR, beta2AR
      beta3AR), each of which is coupled to Galphas and the stimulation of
      intracellular cAMP levels. While beta1AR and beta2AR are broadly expressed
      throughout tissues of the body, beta3AR is found predominantly in adipocytes.
      Stimulation of the betaARs leads to lipolysis in white adipocytes and
      nonshivering thermogenesis in brown fat. However, in essentially all animal
      models of obesity, the betaAR system is dysfunctional and the ability to
      stimulate lipolysis and thermogenesis is impaired. Nevertheless, we and others
      have shown that selective beta3AR agonists are able to prevent or reverse obesity
      and the loss of betaAR expression and to stimulate thermogenesis. This chapter
      will review the current understanding of the role of the sympathetic nervous
      system and the adipocyte betaARs in models of obesity; the physiologic impact of
      changes in betaAR expression on body composition and thermogenesis; and the
      regulation and unique properties of betaAR subtypes in brown and white
      adipocytes. The latter includes our recent discovery of novel signal transduction
      mechanisms utilized by beta3AR to activate simultaneously the protein kinase A
      and MAP kinase pathways. The impact of understanding these pathways and their
      potential role in modulating adaptive thermogenesis is discussed.

PMID- 11237220
TI  - The adipocyte as a secretory organ: mechanisms of vesicle transport and secretory
      pathways.
AB  - Obesity is a common problem in western society that is directly linked to several
      disease processes and is associated with significant morbidity and mortality.
      Adipocytes--the primary site for energy storage (as triglycerides) and release-
      were long suspected to have an active role in regulating body weight homeostasis
      and energy balance. As a result, many studies have focused on finding
      abnormalities in adipocyte physiology and metabolism. An ever-increasing body of
      evidence indicates that, in addition to serving as a repository for energy
      reserves, adipocytes secrete a myriad of factors that comprise a complex network
      of endocrine, autocrine, and paracrine signals. Very little is known regarding
      the molecular mechanisms utilized by the adipocyte in regulating the biosynthesis
      and exocytosis of these secreted products. In order to gain a better
      understanding of these processes, we have examined the two classical secretory
      pathways: regulated and constitutive. Using leptin as a model adipocyte-secretory
      protein, this review focuses primarily on the latter pathway. This includes
      regulation of leptin synthesis and secretion by insulin and glucocorticoids and,
      more recently, the finding that the orexigenic neuropeptide, melanin
      concentrating hormone (MCH), can stimulate leptin synthesis and secretion. This
      chapter also incorporates new data describing the partial purification and effect
      of insulin on leptin-containing vesicles in rat adipocytes. These data indicate
      that the majority of leptin trafficking occurs via a constitutive secretory
      pathway and that the primary acute insulin effect on leptin secretion is to
      increase leptin protein content. In addition, we describe the identification and
      characterization of the vesicle-associated protein, pantophysin, which may play a
      multifunctional role in vesicle biogenesis and transport.

PMID- 11237221
TI  - Central melanocortins and the regulation of weight during acute and chronic
      disease.
AB  - Recent advances in our understanding of the regulation of body weight, appetite,
      and metabolic rate have highlighted the role of the adipose-derived hormone
      leptin and its receptor as fundamental modulators of these processes.
      Investigations of the neural targets for leptin action--as well as
      characterization of the agouti obesity syndrome--have, in turn, led to the
      discovery of fundamental neural pathways involved in the central regulation of
      energy homeostasis. In particular, the central melanocortin system has been shown
      to regulate appetite and metabolic rate in rodents; mutations in this system have
      been demonstrated to result in obesity in humans. Overall, the melanocortin
      system appears to function as a bidirectional rheostat in the regulation of
      energy intake and expenditure in rodents and potentially in humans. The first
      section of this chapter will focus on the development of our understanding of
      melanocortin physiology in the context of obesity. In particular, recent data
      regarding the interplay between melanocortin and neuropeptide Y (NPY) signaling
      at a cellular level will be discussed. The following section will discuss the
      hypothesis that melanocortin signaling plays a role in pathological weight loss
      and hypermetabolism observed in murine cachexia models. The potential role of
      this system in integrating a variety of anorexic and cachexic signals, as well as
      the potential for its pharmacological manipulation in the treatment of human
      cachexia, will be discussed.

PMID- 11237222
TI  - Glucagon-like peptide-1.
AB  - There is a progressive impairment in beta-cell function with age. As a result, 19
      percent of the U.S. population over the age of 65 is diagnosed with type 2
      diabetes mellitus (DM). Glucagon-like peptide-1 (GLP-1) is a potent insulin
      secretagogue that has multiple synergetic effects on the glucose-dependent
      insulin secretion pathways of the beta-cell. This peptide and its longer-acting
      analog exendin-4 are currently under review as treatments for type 2 DM. In our
      work on the rodent model of glucose intolerance in aging, we found that GLP-1 is
      capable of rescuing the age-related decline in beta-cell function. We have shown
      that this is due to the ability of GLP-1 to 1) recruit beta-cells into a
      secretory mode; 2) upregulate the genes of the beta-cell glucose-sensing
      machinery; and 3) cause beta-cell differentiation and neogenesis. Our
      investigations into the mechanisms of action of GLP-1 began by using the reverse
      hemolytic plaque assay to quantify insulin secretion from individual cells of the
      RIN 1046-38 insulinoma cell line in response to acute treatment with the peptide.
      GLP-1 increases both the number of cells secreting insulin and the amount
      secreted per cell. This response to GLP-1 is retained even in the beta cell of
      the old (i.e., 22-month), glucose-intolerant Wistar rat, which exhibits a normal,
      first-phase insulin response to glucose following an acute bolus of GLP-1.
      Preincubation with GLP-1 (24 hours) potentiates glucose- and GLP-1-dependent
      insulin secretion and increases insulin content in the insulinoma cells.
      Treatment of old Wistar rats for 48 hours with GLP-1 leads to normalization of
      the insulin response and an increase in islet insulin content and mRNA levels of
      GLUT 2 and glucokinase. PDX-1, a transcriptional factor activator of these three
      genes, also is upregulated in the insulinoma cell line in aged rats and diabetic
      mice following treatment with GLP-1. Administration of GLP-1 to old rats leads to
      pancreatic cell proliferation, insulin-positive clusters, and an increase in beta
      cell mass. This evidence led us to believe that GLP-1 is an endocrinotrophic
      factor. We used an acinar cell line to show that GLP-1 can directly cause the
      conversion of a putative pro-endocrine cell into an endocrine one. Thus, the
      actions of GLP-1 on the beta-cell are complex, with possible benefits to the
      diabetic patient that extend beyond a simple glucose-dependent increase in
      insulin secretion. The major limitation to GLP-1 as a clinical treatment is its
      short biological half-life. We have shown that the peptide exendin-4, originating
      in the saliva of the Gila monster, exhibits the same insulinotropic and
      endocrinotrophic properties as GLP-1 but is more potent and longer acting in
      rodents and humans.

PMID- 11237223
TI  - Leptin controls bone formation through a hypothalamic relay.
AB  - Menopause favors osteoporosis and obesity protects from it. In an attempt to
      decipher the molecular bases of these two well-known clinical observations, we
      hypothesized that they meant that bone remodeling, body weight, and reproduction
      are controlled by identical endocrine pathways. We used mouse genetics as a tool
      to translate these clinical observations into a molecular hypothesis. The ob/ob
      and db/db mice were valuable models, since two of the three functions thought to
      be co-regulated are affected in these mice: they are obese and hypogonadic.
      Surprisingly, given their hypogonadism, both mouse mutant strains have a high
      bone mass phenotype. Subsequent analysis of the mechanism leading to this high
      bone mass revealed that it was due to an increase of bone formation. All data
      collected indicate that, in vivo, leptin does not act directly on osteoblasts but
      rather through a central pathway following binding to its specific receptors
      located on hypothalamic nuclei. This result revealed that bone remodeling, like
      most other homeostatic functions, is under hypothalamic control. The nature of
      the signal downstream of the hypothalamus is unknown but current experiments are
      attempting to identify it.

PMID- 11237224
TI  - Mechanisms of inhibin signal transduction.
AB  - Inhibin was first identified as a gonadal hormone that potently inhibits
      pituitary follicle-stimulating hormone (FSH) synthesis and secretion. Although
      the notion of a nonsteroidal, gonadally derived inhibitory substance was realized
      in the early 1930s (McCullagh, 1932), identification of the hormone was not
      accomplished until more than 50 years later. At that time, inhibin was purified
      from bovine and porcine follicular fluid and was shown to be produced in two
      forms through dimeric assembly of an alpha subunit (18 kDa) and one of two
      closely related beta subunits (betaA and betaB, approximately 14 kDa) (Ling et
      al., 1985; Miyamoto et al., 1985; Rivier et al., 1985; Robertson et al., 1985).
      Dimers of alpha and betaA and alpha and betaB subunits form inhibin A and inhibin
      B, respectively. In the process of purifying inhibin, two groups also identified
      homo- and heterodimers of the inhibin beta subunits (Ling et al., 1986; Vale et
      al., 1986). These hormones, the activins, were shown to potently stimulate FSH
      secretion from primary pituitary cultures and are now known to play important
      roles in growth and development (Woodruff, 1998; Pangas and Woodruff, 2000).
      Inhibins and activins are considered members of the transforming growth factor
      beta (TGF-beta) superfamily of growth and differentiation factors, based on a
      pattern of conserved cysteine residues in the alpha and beta subunits, similar to
      other ligands in the family. Identification of the subunit proteins led to the
      cloning of their cDNAs and subsequently to their chromosomal mapping in several
      species (Mason et al, 1985,1986; Forage et al., 1986; Mayo et al., 1986; Esch et
      al., 1987; Woodruff et al., 1987; Barton et al., 1989; Hiendleder et al., 2000).
      Three additional activin-related beta subunits (betaC and betaE in mammals and
      betaD in Xenopus laevis) also have been identified but do not appear to play a
      role in FSH regulation (Hotten et al., 1995; Oda et al., 1995; Fang et al., 1996,
      1997; Loveland et al., 1996; Schmitt el al., 1996; O'Bryan et al., 2000; Lau et
      al., 2000). To date, only one alpha subunit has been reported. The inhibin
      subunits are expressed in various tissues (Meunier et al., 1988a, 1988b) but the
      gonads are clearly the primary source of circulating inhibins (Woodruff et al.,
      1996). While inhibins act in a paracrine role in some tissues (Hsueh et al.,
      1987), their best-understood roles are as endocrine regulators of pituitary FSH.
      Activins also were purified from follicular fluid but because circulating activin
      levels generally are low, most actions of the hormones are likely to be paracrine
      in nature (Woodruff, 1998). Several reviews in the past decade have clearly and
      thoroughly addressed the characterization and regulation of the inhibins and
      activins and their roles in reproductive function (Vale et al., 1988; Ying, 1988;
      Woodruff and Mayo, 1990; Mayo, 1994; Woodruff and Mather, 1995). In this chapter,
      we focus our attention on more-recent developments in inhibin research. First, we
      discuss differential regulation of inhibin isoforms. Specifically, we describe
      patterns of inhibin A and B secretion in the context of the female reproductive
      cycle. Second, we review molecular mechanisms of inhibin subunit regulation.
      Third, while inhibins are best known for their role in pituitary FSH regulation,
      other functions of the ligands are becoming better understood. We review the
      animal and human literature addressing the possible role of inhibins in gonadal
      cancers. While we know "what" inhibins do in various contexts, we have a very
      limited understanding of "how" the ligands have their effects on target cells.
      Recently, candidate inhibin receptor molecules have been identified (Draper et
      al., 1998; Hertan et al., 1999; Lewis et al., 2000; Chung et al., 2000). Next, we
      detail our current understanding of inhibin signal transduction. Finally, in
      light of the data reviewed here, we pose questions and outline future directions
      for inhibin research. While this review is concerned primarily with expression
      and function of inhibin, activin function and mechanisms of action are described
      where necessary to shed light on inhibin function. Several reviews of activin's
      role in reproductive and other processes can be found elsewhere (Woodruff, 1998;
      Pangas and Woodruff, 2000).

PMID- 11237225
TI  - Of mice and men: K(ATP) channels and insulin secretion.
AB  - K(ATP) channels are a unique, small family of potassium (K+)-selective ion
      channels assembled from four inward rectifier pore-forming subunits, K(IR)6.x,
      paired with four sulfonylurea receptors (SURs), members of the adenosine
      triphosphate (ATP)-binding cassette superfamily. The activity of these channels
      can be regulated by metabolically driven changes in the ratio of adenosine
      diphosphate (ADP) to ATP, providing a means to couple membrane electrical
      activity with metabolism. In pancreatic beta cells in the islets of Langerhans,
      K(ATP) channels are part of an ionic mechanism that couples glucose metabolism to
      insulin secretion. This chapter 1) briefly describes the properties of K(ATP)
      channels; 2) discusses data on a genetically recessive form of persistent
      hyperinsulinemic hypoglycemia of infancy (PHHI), caused by loss of beta-cell
      K(ATP) channel activity; and 3) compares the severe impairment of glucose
      homeostasis that characterizes the human phenotype with the near-normal phenotype
      observed in K(ATP) channel null mice.

PMID- 11237226
TI  - Genetics of type 1A diabetes.
AB  - Type 1A diabetes is an autoimmune disease with genetic and environmental factors
      contributing to its etiology. Twin studies, family studies, and animal models
      have helped to elucidate the genetics of autoimmune diabetes. Most of the genetic
      susceptibility is accounted for by human leukocyte antigen (HLA) alleles. The
      most-common susceptibility haplotypes are DQA1*0301-DQB1*0302 and DQA1*0501
      DQB1*0201. Less-common haplotypes such as DQA1*0401-DQB1*0402 and DQA1*0101
      DQB1*0501 are associated with high risk for diabetes; however, large study
      populations are needed to analyze their effect. The DQA1*0102-DQB1*0602 haplotype
      is associated with diabetes resistance. DR molecules, such as DRB1*1401, confer
      protection from diabetes. Monozygotic twins of patients with type 1A diabetes
      have a diabetes risk higher than that for HLA-identical ordinary siblings,
      suggesting that non-HLA genes contribute to diabetes risk. Polymorphisms in the
      regulatory region of the insulin gene (designated IDDM2), polymorphisms in
      cytotoxic T lymphocyte antigen-4 (CTLA-4) gene (IDDM12), and other genes are
      likely to contribute to diabetes risk and susceptibility in some individuals. In
      selected families, major diabetogenes (e.g., IDDM17, autoimmune regulator gene
      (AIRE)) are likely to be of importance. Other factors--either noninherited genes
      (i.e., somatic mutations and T-cell receptor or immunoglobulin rearrangements) or
      environment--may have a role in progression to diabetes. This is suggested by the
      finding that the risk for monozygotic twins of patients with type 1A diabetes is
      not 100 percent. Studying the genetics of type 1A diabetes will allow us to
      better define this disease, to improve our ability to identify individuals at
      risk, and to predict the risk of associated disorders.

PMID- 11237227
TI  - Genetic determinants of type 2 diabetes.
AB  - Hyperglycemia of type 2 diabetes mellitus (T2DM) results from a complex interplay
      of genetic and environmental factors that influence a number of intermediate
      traits (e.g., beta-cell mass, insulin secretion, insulin action, fat
      distribution, obesity). The primary biochemical events leading to diabetes are
      still unknown in most cases. Although several monogenic forms of diabetes have
      been identified, T2DM seems to be a polygenic disorder in the majority of cases.
      T2DM is probably also multigenic, meaning that many different combinations of
      gene defects may exist among diabetic patients. Significant results were obtained
      in the identification of the genetic determinants of monogenic forms of diabetes
      with young age of onset. However, despite the evidence for a strong genetic
      background, little of the genetic risk factors for the more-common forms of
      polygenic T2DM are known to date. The goal of this chapter is to summarize and
      discuss the significant results of recent literature on the genetics of both the
      monogenic and polygenic forms of T2DM.

PMID- 11237228
TI  - Treatment of attention-deficit hyperactivity disorder.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a common disorder among
      children and adolescents with reported prevalence rates of between 3 and 10%.
      Recent reports suggest that a multimodal treatment approach is preferable to
      address many symptoms of ADHD and its associated problems for the children, the
      family, and the school. Stimulant medications remain the mainstay of treatment
      and are highly effective in more than 75% of patients. Improvement in the core
      symptoms of inattention, impulsivity, and hyperactivity are most noticeable.
      Recently approved extended release preparation of methylphenidate will allow once
      a day dosing. Reports of effectiveness of some non-stimulant medications such as
      bupropion, especially for adolescents, appear promising. A number of behavioral
      and psychosocial interventions can be used effectively as part of multimodal
      approach to address many ADHD-related problems. This article provides an update
      on practical information on the treatment of children and adolescents with ADHD
      who do not have other associated psychiatric disorders.

PMID- 11237229
TI  - Postpneumonic empyema in childhood.
AB  - Fifty-six patients with postpneumonic empyema were treated by
      sulbactam/ampicillin or cephalothin and netilmicin. Dose of sulbactam/ampicillin
      was 200 mg/kg per day and of cephalothin was 200 mg/kg per day, and of netilmicin
      was 5 mg/kg per day. Sulbactam/ampicillin alone was used in 27 patients. Twenty
      nine patients were treated with cephalothin plus netilmicin. Days on intravenous
      antibiotics, days with chest tube, decortication rate, and duration of
      hospitalization were significantly shorter in sulbactam/ampicillin treatment
      group compared to cephalothin plus netilmicin group. This study shows that
      sulbactam/ampicillin is a safe and effective agent in the treatment of
      postpneumonic empyema in childhood.

PMID- 11237230
TI  - Meropenem in neonatal severe infections due to multiresistant gram-negative
      bacteria.
AB  - Recently, new broad spectrum carbapenem has been investigated on a world-wide
      scale for the treatment of moderate to severe infections. In the neonatal
      intensive care units the extensive use of third generation cephalosporins for
      therapy of neonatal sepsis may lead to rapid emergence of multiresistant gram
      negative organisms. We report the use of meropenem in 35 infants with severe
      infections due to Acinetobacter baumanii and Klebsiella pneumoniae. All gram
      negative bacteria were resistant to ampicillin, amoxicillin, ticarcilin,
      cefazoline, cefotaxime, ceftazidime, ceftriaxone and aminoglycosides. Eighty two
      percent of the cases (29/35) were born prematurely. Assisted ventilation was
      needed in 85.7% (30/35). All infants deteriorated during their conventional
      treatment and were changed to meropenem monotherapy. Six percent (2/35) died. The
      incidence of drug-related adverse events (mostly a slight increase in liver
      enzymes) was 8.5%. No adverse effects such as diarrhea, vomiting, rash,
      glossitis, oral or diaper area moniliasis, thrombocytosis, thrombocytopenia,
      eosinophilia and seizures were observed. At the end of therapy, overall
      satisfactory clinical and bacterial response was obtained in 33/35 (94.3%) of the
      newborns treated with meropenem. Clinical and bacterial response rates for
      meropenem were 100% for sepsis and 87.5% for nosocomial pneumonia. This report
      suggests that meropenem may be a useful antimicrobial agent in neonatal
      infections caused by multiresistant gram negative bacilli. Further studies are
      needed to confirm these results: Meropenem, newborn, sepsis and nosocomial
      infection.

PMID- 11237232
TI  - Fetal gastrointestinal malformations.
AB  - In an audit to evaluate fetal gastrointestinal (GIT) malformations, case sheets
      of all mothers who gave birth to newborns with GIT malformations were analysed
      regarding the maternal history, prenatal ultrasound and the postnatal structural
      malformations and perinatal management. In 1999, eleven babies were born with
      gastrointestinal malformations, one was a still birth. Nine had associated
      malformations of other systems, two had trisomy 21. Eight babies were operated in
      the immediate newborn period, 5 survived. Ultrasound was not very accurate in the
      diagnosis of GIT anomaly in this series. In view of associated chromosomal and
      structural anomaly a fetal ECHO and genetic amniocentesis is warranted. Most of
      these babies require immediate surgery after birth, so they need to be delivered
      in a centre which is equipped with good neonatal and pediatric surgery care.

PMID- 11237231
TI  - BCG revaccination and tuberculin reactivity.
AB  - Interpretation of tuberculin reactions in revaccinated children is somewhat
      controversial among paediatricians. In this study, the effect of the number of
      BCG vaccines on tuberculin reactivity is evaluated. In 2810 healthy children aged
      7 to 14 years with purified protein derivative (PPD) testing. Children were
      grouped according to the concordance of the number of the reported/documented
      vaccinations to the number of scars. Group 1 and 2 comprised of children 7 to 10
      years of age and 11 to 14 years of age respectively, who had non-concordant scar
      numbers, and Group 3 and 4 included 7 to 10 and 11 to 14 years old children with
      concordant scar numbers. Mean tuberculin induration sizes were 8.0 +/- 5.7 mm for
      Group 1, 10.6 +/- 4.9 mm for Group 2, 9.8 +/- 4.9 mm for Group 3 and 10.9 +/- 4
      mm for Group 4. As the time interval after the last dose of vaccination
      increased, mean induration sizes decreased in Group 1 and Group 3. In contrast,
      the mean reaction sizes of Group 2 and Group 4 showed a positive correlation with
      the period after the last dose of vaccine. It seems advisable that an induration
      size > or = 15 mm should not be attributed to BCG vaccination in countries with a
      high tuberculosis infection prevalence and routine BCG revaccination policies. A
      detailed investigation for tuberculosis infection and disease should be performed
      in those cases.

PMID- 11237233
TI  - Non-surgical closure of large ductus arteriosus using Amplatzer Duct Occluder
      feasibility and early follow-up results.
AB  - The aim of the study was the assess feasibility of closing large patent arterial
      ducts (PDA) in infants and children using the new Amplatzer Duct Occluder. All
      patients diagnosed to be having PDA were considered as potential candidates to
      undergo the device closure. 19 patients were diagnosed to be having PDA larger
      than 4 mm. There were 10 males and 9 females, their age ranged from 6 months to
      120 months with a mean of 45 months. Mean body weight was 14.5 kg with a range
      from 7 kg to 23 kg. The procedure was carried out under Ketamine sedation and
      local anesthesia. The device was implanted by the transvenous route in all. Mean
      PDA diameter was 5 mm (range 4 mm-6.7 mm). Complete closure was achieved in 16/18
      (88%) within 24 hours of the procedure. All patient have been followed for 3
      months, and have documented complete closure, there is no evidence of aortic or
      left pulmonary stenosis in any of our patients. The unsuccessful attempt was in a
      malnourished patient (weighing 4.7 kg) with an arterial duct measuring 6.7 mm on
      angiography. This duct was considered too big for device closure and the
      procedure was abandoned. This patient subsequently has undergone successful
      surgical ligation. Catheter closure of large PDA in small children is feasible,
      safe and efficacious. However, it may still not be possible to close large PDA in
      very small or underweight children, for the fear of causing obstruction to the
      descending aorta. Further long-term is follow-up required to show sustained
      benefits without any side effects.

PMID- 11237234
TI  - Efficacy of a home-made spacer with acute exacerbation of bronchial asthma: a
      randomized controlled trial.
AB  - Metered dose inhaler (MDI) with spacer is the preferred method for administration
      of aerosolized medications in pediatric asthma. The expense of commercial spacers
      limits their use and indigenous alternatives have therefore been developed.
      Information on the clinical efficacy of home-made spacers is limited. This study
      was conducted to compare the efficacy of a valve-less home-made spacer with a
      commercial spacer in delivering salbutamol via MDI in acute asthma. Asthmatic
      children aged 5-15 years who presented with an acute exacerbation to the
      pediatric chest clinic of a tertiary care hospital were enrolled in a single
      blinded randomized parallel group study. The study patients received 10 puffs of
      salbutamol (100 microg/puff) via MDI-home-made spacer or MDI-commercial spacer.
      Pre and post inhalation measurements of peak expiratory flow rate (PEFR), oxygen
      saturation (SaO2), respiratory rate (RR), pulse rate (PR) were made and compared.
      Sixty children were enrolled in the study, 31 were administered salbutamol via
      the home-made spacer and 29 via the commercial spacer. The median increase in
      PEFR was similar in both the groups (20.8% vs 22.2%, p=0.4), clinical improvement
      being satisfactory in all patients. The valve-less home-made spacer is equally
      efficacious and cheaper than the commercial spacer in administering
      bronchodilators in acute exacerbations of asthma. Further studies on the efficacy
      of home-made spacer in delivery of inhaled steroids are needed.

PMID- 11237235
TI  - Towards a better oral rehydration fluid.
AB  - Improvements in characteristics of solutions used for oral rehydration therapy,
      to provide significant reductions in amount and duration of diarrhea, are
      expected to contribute to wider use of these fluids. Recent studies suggest that
      these may come about from reducing the osmolality of the solution, and by
      providing short chain fatty acids for better fluid absorption from the colon.
      This article briefly reviews the physiology of intestinal and colonic absorption
      in diarrhea, and indicates the further studies that are needed to translate the
      above advances into universal practice for the treatment of diarrhea.

PMID- 11237236
TI  - Management of severe malnutrition and diarrhea.
AB  - Children with severe malnutrition and diarrhea have high mortality rates that
      have been attributed to faulty case-management. Health workers are often unaware
      of the unique treatment requirements of severely malnourished children resulting
      in improper case-management. Moreover, the lack of prescriptive guidelines
      promotes the exercise of discretion in case-management that is often detrimental.
      Appropriate feeding from the start of treatment, routine micronutrient
      supplementation, broad-spectrum antibiotic therapy, less use of intravenous
      fluids for rehydration, and careful management of complications are factors that
      can reduce death, morbidity and cost of treating children with severe
      malnutrition and acute illnesses including diarrhea. In this paper is discussed a
      standardized protocol based upon the above mentioned factors for the management
      of severely malnourished children with acute illnesses including diarrhea.
      Implementation of the protocol resulted in a 47% reduction in mortality in these
      children.

PMID- 11237238
TI  - Transfusion medicine in the new millennium.

PMID- 11237237
TI  - Tuberculin test.
AB  - Although tuberculin test is widely used for detection of tuberculous infection
      among children, there is no clear understanding about its performance and
      interpretation. This article has been written with the purpose of elucidating the
      performance and interpretation of standard tuberculin test, based on the
      experiences gained at the National Tuberculosis Institute, Bangalore and other
      centres. The standard tuberculin test involves intradermal injection of '1TU PPD
      RT23 with Tween 80' on the mid-volar aspect of forearm and measurement of the
      maximum transverse diameter of induration after 3 days. Larger the size of
      induration, higher is the probability of it being due to tuberculous infection.
      The majority of reactions with induration size of 15 mm and above are
      attributable to infection with tubercle bacilli, irrespective of BCG-vaccination
      status. While indurations of less than 5 mm indicate absence of any kind of
      tuberculin sensitivity, the majority of indurations in 5-9 mm range are usually
      of non-tuberculous nature. An induration of 10-14 mm requires more careful
      interpretation. It is more likely to be attributable to infection with tubercle
      bacilli in case of history of contact with smear positive case or among children
      with clinical findings of tuberculosis. However, the size of induration in an
      infected child may be diminished in the presence of immuno-suppressive
      conditions. One should also consider the purpose of the test while interpreting
      the test results.

PMID- 11237239
TI  - Therapeutic apheresis.
AB  - During the last 30 years in vivo blood cell separation, generally referred to
      apheresis, has established a central role in both blood donor programmes and
      therapeutics. The technological advances in apheresis equipment has made
      procedures safer, faster and more effective. This article will review the use of
      apheresis in clinical medicine with emphasis on plasma exchange and peripheral
      blood stem cell collection. Plasma exchange now has a pivotal role in the
      management of a range of disorders, specially those with autoimmune pathogenesis.
      However, Plasma exchange should be practised as one component of an integrated
      and frequently multidisciplinary approach to management. The harvesting of
      allogeneic or autologous of peripheral blood haemopoietic stem cells is increased
      and it has become the principle indication for apheresis in many haematology
      units. A well coordinated protocol approach to this procedure is important if
      adequate haemopoietic stems cells are to be collected and safely cyropreserved.
      This requires successful cooperation between medical, nursing and scientific
      personnel.

PMID- 11237240
TI  - Are our donors safe?
AB  - Blood is defined as a 'drug' under the Drugs and Cosmetics Act. The Standard of
      drugs is laid down in the Indian Pharmacopoeia. The first step towards blood
      safety is to encourage blood donations, which are voluntary, non-remunerated and
      obtained from low-risk and regular donors. A regular donor is one who donates
      blood two to three times a year and continues to donate at least once a year.
      Over the last 8 years, the Drug Control Authority has been taken up many steps to
      improve the quality of blood in circulation. As a result, blood centres are now
      equipped with minimum modern tests for making blood safer. The inspectors are
      also emphasising the need to employ uniform procedures for donor selection, donor
      deferral, validation of equipment, and so on. Over the last 5 years, quality
      control of diagnostic kits prior to their registration and marketing have been
      streamlined to ensure that blood centres use highly sensitive kits while testing
      for blood transmissible diseases. Therefore, current methods of donor screening
      and testing of donated blood have led to a remarkable decrease in the incidence
      of transfusion-transmitted infection and a blood supply that is very safe. The
      greatest threat to blood safety is donation by seronegative individuals during
      the infectious window period when they are undergoing seroconversion and
      infection cannot be detected by available laboratory tests. Look-backs is the
      process whereby blood collection facilities attempt to indentify prior recipients
      of blood donated by individuals who subsequently test positive TTD. This alone
      can assure safety.

PMID- 11237241
TI  - Leukocyte adhesion deficiency.
AB  - Leukocyte adhesion deficiency is a rare syndrome with autosomal recessive pattern
      of inheritance. An eleven-month-old boy, whose parents were first degree
      relatives, was referred to clinic with recurrent episodes of pneumonia, otitis
      and extensive necrotic wounds of perianal area since neonatal period. His
      umbilical cord had separated 30 days after birth. Laboratory findings included
      marked leukocytosis, chemotaxis abnormality, and very low levels of CD 11 (0.5%)
      and CD 18 (2%). Leukocyte Adhesion Defect (LAD) is rare genetic defect of a group
      of leukocyte membrane glycoproteins. LAD affects nearly one out of every million
      individuals and is characterized by recurrent bacterial and fungal infections of
      skin and mucous membranes, diminished pus formation, delayed umbilical cord
      separation, granulocytosis, poor wound healing and progressive periodontitis.
      This is the first report of a case of LAD in Isfahan of Iran.

PMID- 11237242
TI  - Acute pulmonary edema as a complication of anti-snake venom therapy.
AB  - Polyvalent Anti-snake Venom (ASV) is a life-saving antivenin for severe
      envenomation due to snake bite in India. ASV infusion is occasionally associated
      with severe allergic reactions, i.e. anaphylaxis and death. We report a rare
      instance of non-cardiogenic pulmonary edema due to ASV infusion in an eleven
      years old boy.

PMID- 11237243
TI  - Anterior urethral valves--a rare cause of urethral obstruction.
AB  - Anterior urethral valves is a very rare congenital anomaly of the anterior
      urethra. It produces symptoms of varied intensity with the most severe ones
      leading to Urosepsis and renal failure (similar to as in posterior urethral
      valves) to the milder ones which may not produce any obstruction at all. However
      unlike the Posterior urethral valves this anomaly has milder and reversible
      sequelae in majority of the cases. The clinical presentation is mainly in the
      form of obstructed stream of urine and UTI and the diagnosis depends essentially
      on Micturating Cystographic studies and on the awareness and a high level of
      suspicion of its existence among Paediatricians and General Practitioners.

PMID- 11237244
TI  - Hyperimmunoglobulin E syndrome.
AB  - Hyperimmunoglobulin E (HIE) syndrome is a primary immunodeficiency disorder
      characterized by recurrent bacterial infections in presence of very high serum Ig
      E levels. We are reporting a nine-year-old child with HIE syndrome and reviewing
      literature on this disease.

PMID- 11237245
TI  - Asymptomatic neonatal cholelithiasis.
AB  - Cholelithiasis in neonates and infants has been rarely reported. With the current
      widespread use of diagnostic ultrasonography, more neonates may be found with
      gallstones and common bile duct stones. We describe a case of asymptomatic
      gallstones detected incidentally at the age of four days who presented with early
      onset of neonatal sepsis and dehydration.

PMID- 11237246
TI  - Selective testosterone secreting adrenocortical carcinoma in an infant.
AB  - Adrenocortical carcinoma in children is a rare tumor of adrenal gland. An infant
      presented with signs of virilization due to selective testosterone
      hypersecretion. Diagnosis was established with the help of the computerized
      tomographic scan and histopathological examination. Following adrenalectomy
      patient made uneventful recovery and six months later does not have any clinical
      or laboratory evidence of recurrence or metastasis.

PMID- 11237247
TI  - False results of latex agglutination tests.

PMID- 11237248
TI  - Binding site of Fe3+ at purine of ATP as studied by NMR.
AB  - The binding site of Fe3+ in the purine base of adenosine 5'-triphosphate (ATP)
      was studied by nuclear magnetic resonance (NMR). The NMR relaxation rates (R1) of
      1H and 31P in ATP solutions free of and containing ferric ions were measured in
      the pH range of 3-10. It was found that Fe3+ selectively enhanced the relaxation
      rate of protons. In the presence of Fe3+, the R1 of H2 was much bigger than that
      of H8 at a lower pH (3-4.5), while at a higher pH (5.5-7.5) the R1 of H8 was more
      enhanced than H2. At a pH of around 5, both H2 and H8, as well as all three
      phosphorous, showed a sudden jump in R1. When pH>8, Fe3+ failed to show
      appreciable enhancement of R1 to all protons and phosphorous. The quantitative
      data of relaxation rate enhancements suggest that the binding site of Fe3+ in ATP
      is strongly dependent on pH. At lower pH values, Fe3+ binds N1 but at higher pH
      it binds to N7. When pH is around 5, the whole purine base donates the aromatic
      pi-electrons to the ferric ion, forming a ferrocene-like complex, while when
      pH>8, ATP could not form complexes with Fe3+.

PMID- 11237249
TI  - Interaction between iron(II) and hydroxamic acids: oxidation of iron(II) to
      iron(III) by desferrioxamine B under anaerobic conditions.
AB  - Interaction between iron(II) and acetohydroxamic acid (Aha), alpha
      alaninehydroxamic acid (alpha-Alaha), beta-alaninehydroxamic acid (beta-Alaha),
      hexanedioic acid bis(3-hydroxycarbamoyl-methyl)amide (Dha) or desferrioxamine B
      (DFB) under anaerobic conditions was studied by pH-metric and UV-Visible
      spectrophotometric methods. The stability constants of complexes formed with Aha,
      alpha-Alaha, beta-Alaha and Dha were calculated and turned out to be much lower
      than those of the corresponding iron(II) complexes. Stability constants of the
      iron(II)-hydroxamate complexes are compared with those of other divalent 3d-block
      metal ions and the Irving-Williams series of stabilities was found to be
      observed. Above pH 4, in the reactions between iron(II) and desferrioxamine B,
      the oxidation of the metal ion to iron(III) by the ligand was found. The overall
      reaction that resulted in the formation of the tris-hydroxamato complex
      [Fe(HDFB)]+ and monoamide derivative of DFB at pH 6 is: 2Fe2+ + 3H4DFB+ =
      2[Fe(HDFB)]+ + H3DFB-monoamide+ + H2O + 4H+. Based on these results, the
      conclusion is that desferrioxamine B can uptake iron in iron(III) form under
      anaerobic conditions.

PMID- 11237250
TI  - The EPR spectrum for CuB in cytochrome c oxidase.
AB  - Incubation of cytochrome c oxidase (CcO) in its resting state in saturated
      ammonium sulfate, at room temperature overnight, gave EPR signals characteristic
      of a single Cu(II) center. From the g// and A// values it is concluded that this
      is a square-planar type 2 copper center, and superhyperfine splitting shows the
      presence of three nearly equivalent 14N nuclei in the plane. It is suggested that
      this center, also formed by incubating the enzyme in 10% methanol followed by
      direct irradiation, must be the CuB center. This type 2 copper EPR spectrum is
      identical to the EPR spectrum of CuB reported for the isolated cytochrome bo3
      complex from Escherichia coli; and to the EPR spectrum reported for the
      sulfobetaine 12 heat-treated cytochrome c oxidase complex. It is argued that a
      small perturbation in the system causes decoupling of the magnetic coupling of
      the heme a3-CuB binuclear center and the appearance of the type 2 EPR signal.

PMID- 11237251
TI  - Molecular modeling of the mechanochemical triggering mechanism for catalysis of
      carbon-cobalt bond homolysis in coenzyme B12.
AB  - The possible contributions of the mechanochemical triggering effect to the
      enzymatic activation of the carbon-cobalt bond of coenzyme B12 (5'
      deoxyadenosylcobalamin, AdoCbl) for homolytic cleavage have been studied by
      molecular modeling and semiempirical molecular orbital calculations. Classically,
      this effect has envisioned enzymatic compression of the axial Co-N bond in the
      ground state to cause upward folding of the corrin ring and subsequent sterically
      induced distortion of the Co-C bond leading to its destabilization. The models of
      this process show that in both methylcobalamin (CH3Cbl) and AdoCbl, compression
      of the axial Co-N bond does engender upward folding of the corrin ring, and that
      the extent of such upward folding is smaller in an analog in which the normal 5,6
      dimethylbenzimidazole axial ligand is replaced by the sterically smaller ligand,
      imidazole (CH3(lm)Cbl and Ado(lm)Cbl). Furthermore, in AdoCbl, this upward
      folding of the corrin is accompanied by increases in the carbon-cobalt bond
      length and in the Co-C-C bond angle (which are also less pronounced in
      Ado(Im)Cbl), and which indicate that the Co-C bond is indeed destabilized by this
      mechanism. However, these effects on the Co-C bond are small, and destabilization
      of this bond by this mechanism is unlikely to contribute more than ca. 3 kcal
      mol(-1) towards the enzymatic catalysis of Co-C bond homolysis, far short of the
      observed ca. 14 kcal mol(-1). A second version of mechanochemical triggering, in
      which compression of the axial Co-N bond in the transition state for Co-C bond
      homolysis stabilizes the transition state by increased Co-N orbital overlap, has
      also been investigated. Stretching the Co-C bond to simulate the approach to the
      transition state was found to result in an upward folding of the corrin ring, a
      slight decrease in the axial Co-N bond length, a slight displacement of the metal
      atom from the plane of the equatorial nitrogens towards the "lower" axial ligand,
      and a decrease in strain energy amounting to about 8 kcal mol(-1) for both AdoCbl
      and Ado(Im)Cbl. In such modeled transition states, compression of the axial Co-N
      bond to just below 2.0 A (the distance subsequently found to provide maximal
      stabilization of the transition state by increased orbital overlap) required
      about 4 kcal mol(-1) for AdoCbl, and about 2.5 kcal mol(-1) for Ado(Im)Cbl.
      ZINDO/1 calculations on slightly simplified structures showed that maximal
      electronic stabilization of the transition state by about 10 kcal mol(-1)
      occurred at an axial Co-N bond distance of 1.96 A for both AdoCbl and Ado(Im)Cbl.
      The net result is that this type of transition state mechanochemical triggering
      can provide 14 kcal mol(-1) of transition state stabilization for AdoCbl, and
      about 15.5 kcal mol(-1) for the Ado(Im)Cbl, enough to completely explain the
      observed enzymatic catalysis. These results are discussed in the light of current
      knowledge about class I AdoCbl-dependent enzymes, in which the coenzyme is bound
      in its "base-off" conformation, with the lower axial ligand position occupied by
      the imidazole moiety of an active site histidine residue, and the class II
      enzymes, in which AdoCbl binds to the enzyme in its "base-on" conformation, and
      the pendent 5,6-dimethylbenzimidazole base remains coordinated to the metal
      during Co-C bond activation.

PMID- 11237252
TI  - Synthesis, structure and properties of 1,19-disubstituted tetradehydrocorrin
      cobalt complexes.
AB  - 1,19-Disubstituted tetradehydrocorrins have a ring structure that is closely
      related to the corrin ring found in vitamin B12. We herein report the isolation
      and full characterization of a Co(I)-TDHC species and X-ray crystal structures
      and full characterization of related Co(II) and Co(III) corrins as models for
      vitamin B12 complexes.

PMID- 11237254
TI  - Induction of aerobic peroxidation of liposomal membranes by bis(cyclopentadienyl)
      vanadium(IV) (acetylacetonate) complexes.
AB  - The ability of bis(cyclopentadienyl)-vanadium(IV) (acetylacetonate) (1) to
      initiate oxygen-dependent lipid peroxidation in zwitterionic liposomal membranes
      was examined in detail. A comparison of the rates of the lipid peroxidation
      reaction demonstrated that the electron-donating capacity of the substituted
      acetylacetonate ligand significantly influences the rate of reaction. An increase
      in the rate of lipid peroxidation correlated to a decrease in the V(IV)/V(V)
      redox potential. Notably, lipid peroxidation initiated with 1 proceeded without
      the formation of radicals as shown by EPR spin trap techniques. In contrast,
      lipid peroxidation initiated with non-chelated bis(cyclopentadienyl)-vanadium(IV)
      dichloride (6) was associated with the production of radicals under similar
      experimental conditions. There also was a significant pH effect on the extent of
      peroxidation initiated with 6 versus the reaction initiated with 1. The mode of
      action of 1 likely involves the activation of molecular oxygen by the
      vanadium(IV) center followed by allylic hydrogen atom abstraction from the lipid.

PMID- 11237253
TI  - Cellular effects of transferrin coordinated to.
AB  - Estimates of the net equilibrium binding constants for [(H2O)(NH3)5RuII]2+,
      [Cl(NH3)5RuIII]2+, cis-[(H2O)2(NH3)4RuII]2+ and cis-[Cl2(NH3)4RuIII]+ with
      apotransferrin (Tf) and holotransferrin (Fe2Tf) suggests that RuIII, but not RuII
      complexes bind with a higher affinity to the iron binding sites. Several other
      presumably histidyl imidazole sites bind with approximately the same affinity
      (Keff = 10(2) to 10(3) M(-1) to both RuII and RuIII. Compared to HeLa cells, an
      order of magnitude higher level of nuclear DNA binding ([Ru]DNA/[P]DNA) was
      required to achieve the same level of toxicity in Jurkat Tag cells, which
      probably relates to the substantially higher levels of cis-[Cl2(NH3)4Ru]+ needed
      to inhibit 50% of the cell growth in the Jurkat Tag cell line. Against Jurkat Tag
      cells, the toxicity of the pentaammineruthenium(III) group is enhanced by
      approximately two orders of magnitude upon binding primarily to the Fe-sites in
      apotransferrin, whereas the toxicity of the tetraammineruthenium(III) moiety is
      only marginally increased. Binding to Fe2Tf does not increase the toxicity of
      either group. Significant dissociation over 24 h of the ammineruthenium(III) ions
      from apotransferrin requires reduction to RuII.

PMID- 11237255
TI  - Sugar interaction with metal ions. The crystal structure and Raman spectra study
      of SmCl3-galactitol complex.
AB  - The crystal structure of 2SmCl3.galactitol.14H2O has been determined. The crystal
      system is triclinic, space group: P-1. The unit cell dimensions: a = 9.683(2) A,
      b = 10.341(2) A, c = 7.990(2) A; alpha = 108.01(3) degrees, beta = 92.71(3)
      degrees, gamma = 88.42(3) degrees. Each Sm atom is coordinated to nine oxygen
      atoms, three from the alditol and six from water molecules, with Sm-O distance
      from 2.417 to 2.520 A. The seventh water molecule is hydrogen-bonded by the
      hydroxy hydrogen on O-3 (O(3)-H(13)...O(10), 2.635 A). After forming complexes
      the peaks have shifted and the relative intensities have changed in the IR and
      Raman spectra, which are corresponding to the changes in bond distances and bond
      angles of the structures. The IR and Raman spectra of Pr-, Nd- and Sm-galactitol
      complexes are similar, which show that the three metal ions have the same
      coordination mode.

PMID- 11237256
TI  - Synthesis, characterisation, X-ray structure and biological activity of three new
      5-formyluracil thiosemicarbazone complexes.
AB  - Three new complexes of transition metals as copper, nickel and cobalt with 5
      formyluracil thiosemicarbazone (H3ut) have been synthesised and characterised by
      single-crystal X-ray diffraction. In all compounds the ligand behaves as SNO
      terdentate. In the copper complex the coordination geometry is square pyramidal
      with the ligand lying on the basal plane and two water molecules that complete
      the metal environment, the nickel compound is surrounded by six donor atoms
      (three of the ligand, two water oxygen atoms and a chlorine atom) in an
      octahedral fashion, and cobalt also shows an octahedral geometry but determined
      only by two terdentate ligand molecules. These three compounds have been tested
      on human leukemic cell lines K562 and CEM. The nickel and cobalt complexes have
      demonstrated low activity in cell growth, while the copper complex that is more
      active has been tested also on a third leukemic human cell line (U937), but it
      was not able to induce apoptosis on all cell lines.

PMID- 11237257
TI  - Capillary electrophoretic study of carboplatin and analogues with nucleoside
      monophosphates, di- and trinucleotides.
AB  - Carboplatin (cis-diammine-1,1-cyclobutane-dicarboxylatoplatinum(II)) is the only
      cisplatin (cis-diammine-dichloroplatinum(II)) derivative currently available for
      the treatment of cancer worldwide. The higher stability of the carboxylate ligand
      compared to the coordinated chloride in cisplatin results in a reduced reactivity
      of the molecule. Capillary electrophoresis has been applied for investigating the
      adduct formation of carboplatin and analogues with nucleoside monophosphates, di-
      and trinucleotides. Adduct formation results in a significant shift of the
      absorption maximum to lower energy compared to free nucleotides. Therefore,
      characterization of the analytes was performed by UV additionally to NMR
      spectroscopy. A preference for GMP- and AMP-coordination was found. The ability
      of separating all four common nucleotides and their major platinum adducts in a
      single run demonstrates the suitability of CE for this kind of investigations.

PMID- 11237258
TI  - Potentiometric and spectroscopic studies on the dimethyltin(IV) complexes of 2
      hydroxyhippuric acid.
AB  - Equilibrium and spectroscopic (1H, 13C NMR and 119Sn Mossbauer) studies in
      aqueous solution are reported for dimethyltin(IV) complexes of 2-hydroxyhippuric
      acid (Sal-Gly). Below pH 4, oxygen-coordinated complexes MLH and ML are formed.
      In the pH range 5-8.5, the species MLH(-1), predominates at any metal-to-ligand
      ratio. The ligand exchange of this species is slow on the NMR time scale, which
      allows its structural characterization by NMR spectroscopy: the coordination
      polyhedron around the tin atom is distorted trigonal bipyramidal, with tridentate
      [O-,N-,COO-] coordination of Sal-Gly, involving two equatorial methyl groups. The
      NMR results reveal that the main cause of the distortion of the polyhedron is the
      large CH3-Sn-CH3 angle of 136+/-4 degrees. The presented results supplement the
      data available on the dimethyltin(IV)-promoted amide deprotonation of peptides,
      and provide further arguments for the fundamental role of the carboxylate as an
      anchoring group in this process.

PMID- 11237259
TI  - Cloning, sequence analysis, and characterization of the 'lysyl oxidase' from
      Pichia pastoris.
AB  - Lysyl oxidase from Pichia pastoris has been successfully overexpressed. EPR and
      resonance Raman experiments have shown that copper and TPQ are present,
      respectively. Lysyl oxidase from P. pastoris has a similar substrate specificity
      to the mammalian enzyme (both have been shown to oxidize peptidyl lysine
      residues) and is 30% identical to the human kidney diamine oxidase (the highest
      of any non-mammalian source). This enzyme also has a relatively broad substrate
      specificity compared to other amine oxidases. Molecular modeling data suggest
      that the substrate channel in lysyl oxidase from P. pastoris permits greater
      active site access than observed in structurally-characterized amine oxidases.
      This larger channel may account for the diversity of substrates that are turned
      over by this enzyme.

PMID- 11237260
TI  - Inhibition of human topoisomerase II by the antitumor metallocenes.
AB  - The ability of antitumor active metallocenes Cp2MCl2, (M=Ti, V, Mo, Nb) and the
      biologically inactive derivative (MeCp)2TiCl2, to inhibit the relaxation of
      supercoiled plasmid DNA pBR322 by human topoisomerase II has been studied by gel
      electrophoresis. All metallocenes inhibit the enzyme with maximum inhibition
      observed at 2.0 mM (Cp2TiCl2), 3.0 mM (Cp2MoCl2), 0.2 mM (Cp2NbCl2), 0.25 mM
      (Cp2VCl2) and 2.0 mM (MeCpTiCl2). The implications for the mechanism of antitumor
      activity of the metallocene dihalides are discussed.

PMID- 11237261
TI  - Free radical activity of natural and heat treated amphibole asbestos.
AB  - The amphibole minerals amosite and crocidolite were subjected to calcination and
      to hydrothermal treatment in order to study the effect of these heat treatments
      on the ability of the minerals to trigger formation of free radicals, which is
      known to be a main factor causing asbestosis and other asbestos-induced diseases.
      Free radical activity of the natural and heat treated minerals was studied by
      using supercoiled DNA (pUC18 plasmid) as a target molecule, and also by means of
      EPR spectroscopy. It was shown that after calcination of the natural minerals at
      1073 K their free radical activity was strongly decreased These results, which
      may have relevant consequences for asbestos technology, were correlated with
      concomitant alteration of the structure and surface chemistry of the minerals
      during calcination.

PMID- 11237262
TI  - The in vitro antitumour profile of some 1,2-diaminocyclohexane organotin
      complexes.
AB  - Platinum compounds containing the ligand 1,2-diaminocyclohexane (DACH) such as
      tetraplatin [PtCl4(DACH)] have been found to be active in cisplatin-resistant
      tumour models. In an attempt to develop novel metal-based drugs with a different
      therapeutic profile to cisplatin, we have synthesised a series of tin compounds
      containing the DACH ligand, including the Sn analogue of tetraplatin
      [SnCl4(DACH)], and the di- and monoorganotin complexes [Ph2Sn(OAc)2(DACH)],
      [Bu2Sn(OAc)2(DACH)], [PhSnCl3(DACH)], [BuSn(OAc)3(DACH)], [BuSnCl3(DACH)], and
      [PhSn(OCOCF3)3(DACH)]. Mossbauer and IR spectroscopy indicates that the Sn(DACH)
      complexes are hexacoordinated with a molecular structure similar to that of
      tetraplatin. These compounds were tested for potential antitumour activity
      against a panel of human tumour cell lines, (SW620, SW1116 colon carcinoma, ZR-75
      1 breast carcinoma, HT1376 bladder carcinoma, SKOV-3, PA-1 ovarian carcinoma).
      [Ph2Sn(penicillinate)], [Ph2Sn(OCOCH2NCOCH2NH2)], [Ph2Sn(OAc)2] were included for
      comparison. The results show that whereas [SnCl4(DACH)] and the monoorganotin
      complexes had limited or no activity, the diorganotin DACH complexes were
      cytotoxic with an associated increase in potency on going from diphenyl to
      dibutyltin, with mean IC50 values of 7.26+/-4.09 micromol ml(-1) for
      [Ph2Sn(OAc)2(DACH)] and 2.58+/-0.83 micromol ml(-1) for [Bu2Sn(OAc)2(DACH)]
      across the cell line panel. Comparison with [Ph2Sn(OAc)2] (IC50 0.69-0.43
      micromol ml(-1)) indicated that addition of the DACH ligand resulted in a
      decrease in cytotoxicity but increased differential toxicity across the cell line
      panel. These results indicate that the diorganotin DACH complexes merit further
      investigation as potential metal-based antitumour drugs.

PMID- 11237263
TI  - Redox properties and acid-base equilibria of zucchini mavicyanin.
AB  - The reduction potential of mavicyanin isolated from zucchini peelings, which is a
      blue copper protein belonging to the subclass of the phytocyanins, has been
      determined through direct electrochemistry as a function of temperature and pH.
      The enthalpy and entropy changes accompanying protein reduction were found to be
      very similar with those determined previously for other phytocyanins and to
      differ remarkably from those of azurins and plastocyanins. This finding
      contributes to further characterize phytocyanins as a distinct cupredoxins family
      also on thermodynamic grounds and improves our understanding of how the reduction
      potential of these metal centers in proteins is modulated by coordinative and
      solvation properties. The E degrees' of mavicyanin is found to be sensitive to
      two acid-base equilibria at the extremes of pH. One occurs below pH 4, and is
      related to the protonation and detachment from the Cu(I) center of a histidine
      ligand. The other, observed above pH 8, causes a remarkable change in the
      electrostatic potential and/or the field strength around the copper.

PMID- 11237264
TI  - The interaction of tributyllead with lysosomes from rat liver.
AB  - The interactions of tributyllead with lysosomes from rat liver have been studied.
      It results that the organometal compound induces a fast alkalinization in
      energized lysosomes. The interpretation is that the compound is a potent proton
      carrier. This function could explain the toxicity, in particular at neurological
      level of the compound.

PMID- 11237265
TI  - Metals in Medicine: a review of the symposium.

PMID- 11237266
TI  - Solution equilibria and structural characterisation of the palladium(II) and
      mixed metal complexes of peptides containing methionyl residues.
AB  - Palladium(II) complexes of the peptides GlyMet, GlyMetGly and GlyGlyMet
      containing methionyl residues were studied by potentiometric and 1H NMR
      spectroscopic methods. The coordination of terminal amino and deprotonated amide
      nitrogen and thioether sulfur donor atoms was suggested in the mono complexes of
      GlyMet and GlyMetGly. The fourth coordination site of these complexes can be
      occupied by solvent molecule, chloride or hydroxide ions or by another ligand
      molecule in the bis or mixed ligand complexes. The second ligand coordinates
      monodentately via the thioether function in acidic media and the amino group
      under neutral or basic conditions. The stoichiometry of the major species formed
      in the palladium(II)-GlyGlyMet system is [PdH(-2) L]- and this is coordinated by
      the amino, two-amide and the thioether donor functions. Thioether bridged mixed
      metal complexes formed in the reaction of [Pd(dien)]2+ and [Cu(GlyMetH(-1))] or
      [Ni(GlyMetGlyH(-2))]- also have been detected by spectroscopic techniques.

PMID- 11237267
TI  - Synthesis and antitumour activity of platinum(II) and platinum(IV) complexes
      containing ethylenediamine-derived ligands having alcohol, carboxylic acid and
      acetate substituents. Crystal and molecular structure of [PtL4CL2].H20 where L4
      is ethylenediamine-N,N'-diacetate.
AB  - Several cisplatin analogues of ethylenediamine-derived ligands containing
      alcohol, carboxylic acid and acetate substituents have been prepared and
      characterised. Oxidation of some of these square planar platinum(II) complexes
      using aqueous hydrogen peroxide gave octahedral platinum(IV) complexes,
      containing trans hydroxo ligands. Acetylation of the hydroxo ligands was achieved
      by reaction with acetic anhydride, giving complexes which are analogues of the
      antitumour drug, JM-216. Oxidation of the complex [Pt(H2L4)Cl2], where H2L4 is
      ethylenediamine-N,N'-diacetic acid, with H2O2 gave the platinum(IV) complex
      [PtL4Cl2].H2O in which L4 is tetradentate as shown by a crystal and molecular
      structure. This complex was previously reported to be [Pt(HL4)(OH)Cl2] in which
      HL4 is tridentate. Several of the complexes were tested for antitumour activity
      against five human ovarian carcinoma cell lines. IC50 values range from 4.0
      microM for cis,trans-PtCl2(OH)2(NH2CH2CH2NHCH2CH2OH) against the CH1 cell line to
      >25 microM indicating moderate to low activity relative to other platinum
      complexes.

PMID- 11237268
TI  - Physiatric misnomers.

PMID- 11237269
TI  - Functional assessment in patients with chronic pain: can physicians predict
      performance?
AB  - OBJECTIVES: To determine the appropriateness of using physicians to estimate the
      functional abilities of patients with chronic pain. Specific objectives included
      the following: (1) to compare the physician's predicted performance on functional
      assessment with actual performance, and (2) to compare the physician's predicted
      effort during functional assessment with an objective measure of effort. DESIGN:
      A total of 201 outpatients with chronic pain completed this prospective,
      multicenter, cohort study. Fifteen physicians, who were trained to administer the
      standardized evaluation, performed the evaluations and predicted performance and
      effort on functional assessment. Therapists, blinded to the physician's
      evaluation, administered a functional assessment (maximal and sustained lifts [n
      = 3 types]; repetitive activities [n = 4 types]) and a grip dynamometry test
      (effort measure) on each subject. RESULTS: Pearson's correlation testing
      demonstrated significant correlations between the physician's predicted
      performance and the observed performance for all lifting items and repetitive
      activities in both men (0.52, 0.50, 0.55) and women (0.36, 0.40, 0.18). Analysis
      of variance and post hoc t tests showed agreement between the physician's
      predicted effort and the dynamometry effort measure in only a small subset of
      patients (men were predicted to put forth absolutely no effort; n = 4).
      CONCLUSIONS: A trained physician, performing a standardized evaluation, can
      estimate with reasonable accuracy the work-related functional ability in patients
      with chronic pain. The prediction of effort seems to be more problematic.

PMID- 11237270
TI  - Prevention of secondary osteoporosis postmenopause in hemiplegia.
AB  - OBJECTIVES: To study secondary osteoporosis postmenopause in women with
      hemiplegia and to show the therapeutic effects of etidronate and how osteoporotic
      conditions relate to the activities of daily living (ADL). DESIGN: Eighty-one
      postmenopausal women with hemiplegia were admitted within 6 mo of their first
      cerebrovascular accident. The bone mineral density (BMD) and biochemical markers
      of bone turnover were measured at the time of admission. Forty women (treatment
      group) received a 2-wk administration of etidronate. Forty-one women (control
      group) were not administered etidronate. RESULTS: After completing a 3-mo
      rehabilitation program, BMD levels were remeasured. ADL was evaluated by FIM. The
      low ADL group had a larger decrease in BMD than the high ADL group. For the
      control group, the BMD rate of change on the paretic side of the femoral neck was
      -9.6%/3 mo for the low ADL group. BMD loss was reduced significantly by the
      administration of etidronate for the low ADL group. CONCLUSIONS: Results indicate
      that ADL corresponds to the progression of osteoporosis in postmenopausal women
      with hemiplegia and that increasing the level of ADL will reduce the progression
      of osteoporosis. Use of etidronate has also been proven to have a suppressive
      effect on the BMD decrease in women.

PMID- 11237271
TI  - Myofiber injury and regeneration in a canine homologue of Duchenne muscular
      dystrophy.
AB  - OBJECTIVE: To test the hypothesis that differential skeletal muscle involvement,
      previously observed in dogs with a homologue of Duchenne muscular dystrophy,
      correlates with the histochemical markers of myofiber injury and regeneration.
      DESIGN: Evidence of injury (cellular penetration by Evans blue dye,
      immunoglobulin G expression, hematoxylin and eosin staining of necrotic figures),
      myofiber regeneration (fetal myosin heavy chain isoform expression), and
      morphologic indices in the cranial sartorius (CS), long digital extensor, and
      vastus lateralis muscles were examined in five dogs with dystrophy and five
      normal dogs. RESULTS: Only the CS muscle, at 1 mo, demonstrated significant
      differences in injury when compared with age-matched controls. By 6 mo, the long
      digital extensor and vastus lateralis also suffered greater than normal injury.
      Only the dystrophic CS tissue expressed a notable increase in mean myofiber
      diameter when compared with other muscles at 6 mo. Normal CS muscles revealed a
      distinct population of small myofibers at this age. CONCLUSION: The CS seems
      unique in its selective pathologic involvement. These differences may contribute
      to the marked regenerative response of this muscle in the dystrophic state. An
      improved understanding of mechanisms by which some dystrophin-deficient canine
      muscles remain spared from injury may provide clues to investigate and prevent
      the degenerative processes in humans.

PMID- 11237272
TI  - Therapeutic zygapophyseal joint injections for headaches emanating from the C2-3
      joint.
AB  - OBJECTIVE: To report our experience using fluoroscopically guided therapeutic
      intra-articular C2-3 zygapophyseal joint injections in patients with chronic
      headaches after a whiplash event. DESIGN: Restrospective study (n = 18 patients)
      with independent clinical review. Each patient experienced persistent daily
      headache symptoms which failed to improve after at least 3 mo of physical
      therapy, activity restriction, and the use of oral analgesics. Each patient
      demonstrated initially a positive response to a diagnostic intra-articular C2-3
      joint injection. Data collection and analysis were performed by an independent
      clinical reviewer. Outcome measures included headache frequency, medication
      usage, symptom response to medication, and employment status. RESULTS: Patients'
      symptom duration before diagnostic injection averaged 34 mo. Follow-up data
      collection transpired at an average of 19 mo after the final therapeutic
      injection. In 61% of patients, fewer than three headaches were experienced each
      week; these headaches were relieved with the use of oral analgesics. CONCLUSIONS:
      Although the inherent limitations of this study preclude a definitive statement
      regarding the efficacy of C2-3 injections, these initial findings suggest that
      therapeutic intra-articular zygapophyseal joint injections are effective in the
      treatment of headaches emanating from the C2-3 joint after a whiplash event.
      Future controlled, prospective studies are necessary to clarify the role of such
      injections in this challenging patient population.

PMID- 11237273
TI  - Consistency of performance on the functional capacity assessment: static strength
      and dynamic endurance.
AB  - OBJECTIVE: To explore the degree of consistency in a subject's performance in
      physical strength and endurance. DESIGN: Thirty healthy men, aged 19 to 26 yr,
      were recruited to participate in protocols to assess static strength and dynamic
      endurance tests on their upper limbs with the Baltimore Therapeutic Equipment
      Primus. Retests were conducted 7 days after the initial test. RESULTS: The
      intraclass correlation coefficients were 0.71 to 0.97 and 0.32 to 0.90 for static
      and dynamic endurance strengths, respectively. These results indicated that the
      consistency of the subjects' performance across occasions was high for testing
      static strength, although it was more varied for testing endurance strength.
      CONCLUSIONS: Higher consistency was observed among subjects in the assessment of
      static strength than dynamic endurance strength. The range of motion traveled by
      the limb, speed of performance, and ergonomic design of attachments seemed to
      confound the subjects' performance on the instrument. Stringent assessment
      protocols, ergonomically designed hardware, and clear instructions and practice
      trials before the formal testing were essential to maximize the subjects'
      consistency of performance. The results of this study were applicable and
      generalized to other performance-based instruments for physical and functional
      capacity evaluation and work simulators.

PMID- 11237274
TI  - Factor analysis of an outcome interview for use in clinical trials of
      traumatically brain-injured patients: a preliminary study.
AB  - OBJECTIVE: To study the factor structure, internal consistency, concurrent
      validity, and sensitivity to detect change in patient report of problems of a
      structured interview in relationship with accepted outcome measures. DESIGN:
      Outcome status of patients with severe traumatic brain injury participating in a
      randomized, phase III, multicenter clinical trial was assessed at 6 mo postinjury
      using the Glasgow Outcome Scale, the Disability Rating Scale, and the Severe
      Traumatic Brain Injury Outcome Interview. RESULTS: Exploratory factor analysis of
      the Severe Traumatic Brain Injury Outcome Interview produced a meaningful five
      factor model: (1) activities of daily living; (2) cognitive; (3) affective; (4)
      behavioral; and (5) instrumental activities of daily living. The internal
      consistency of the factors ranged from moderate (0.61 instrumental activities of
      daily living) to high (0.94 activities of daily living); the interfactor
      correlations were moderate. The summed factor scores were significantly
      correlated with measures of global outcome: the Glasgow Outcome Scale (r = 0.66;
      P < 0.0001) and the Disability Rating Scale (r = 0.61; P < 0.0001). Patient
      report of cognitive problems correlated moderately with the neuropsychological
      tests. The summed factor scores were sensitive to change over time. CONCLUSIONS:
      Overall, the interview assessed the major important features of outcome pertinent
      to traumatic brain injury and demonstrated greater sensitivity to subtle changes
      over time than the unidimensional approaches, such as the Glasgow Outcome Scale
      and Disability Rating Scale.

PMID- 11237275
TI  - Improvement of thigh muscles by neuromuscular electrical stimulation in patients
      with refractory heart failure: a single-blind, randomized, controlled trial.
AB  - OBJECTIVE: To determine the impact of an 8-wk neuromuscular stimulation program
      of thigh muscles on strength and cross-sectional area in patients with refractory
      heart failure listed for transplantation. DESIGN: Forty-two patients with a
      stable disease course were assigned randomly to a stimulation group (SG) or a
      control group (CG). The stimulation protocol consisted of biphasic symmetric
      impulses with a frequency of 50 Hz and an on/off regime of 2/6 sec. RESULTS:
      Primary outcome measures were isometric and isokinetic thigh muscle strength and
      muscle cross-sectional area. Our results showed an increase of muscle strength by
      mean 22.7 for knee extensor and by 35.4 for knee flexor muscles. The CG remained
      unchanged or decreased by -8.4 in extensor strength. Cross-sectional area
      increased in the SG by 15.5 and in the CG by 1.7. CONCLUSIONS: Activities of
      daily living as well as quality of life increased in the SG but not in the CG.
      Subscales of the SF-36 increased significantly in the SG, especially concerning
      physical functioning by +7.5 (1.3-30.0), emotional role by +33.3 (0-66.6), and
      social functioning by +18.8 (0-46.9), all P < 0.05. Neither a change nor a
      decrease was observed in the CG. Neuromuscular electrical stimulation of thigh
      muscles in patients with refractory heart failure is effective in increasing
      muscle strength and bulk and positively affects the perception of quality of life
      and activities of daily living.

PMID- 11237276
TI  - Roadmap to physical medicine and rehabilitation: answers to medical students'
      questions about the field.
AB  - Medical specialty training has undergone dramatic changes in the last 5 yr. This
      article was prepared by the Undergraduate Education Committee of the Association
      of Academic Physiatrists in an attempt to help guide medical students who are
      considering a career in physical medicine and rehabilitation. This report is an
      update of two previous articles addressing medical students' questions to assist
      them in making educated decisions about residency training and medical practice.

PMID- 11237277
TI  - Measuring professionalism in a physiatry residency training program.
AB  - A 12-item questionnaire modeled after the one prepared by the American Board of
      Internal Medicine dealing with professionalism was distributed to 122 physiatry
      residents representing six training programs, of whom 59% (72) responded. The
      mean item score on the survey was 7.7 (SD = 1.0) on a scale from 1 to 10, where
      10 represents the highest level of professionalism. The internal reliability of
      the questionnaire was found to be satisfactory (Cronbach's alpha = 0.75). A
      factor analysis of the questionnaire items resulted in three factors explaining
      64% of the variance. These factors were: excellence, honor/integrity, and
      altruism/respect; Eigen values were 3.35, 2.37, and 1.31, respectively. These
      factors are similar to those obtained in the American Board of Internal Medicine
      survey. This similarity is a positive feature in ongoing efforts to develop a
      reliable tool for measuring professionalism in physiatry residency training.

PMID- 11237278
TI  - Phlebotomy-related lateral antebrachial cutaneous nerve injury.
AB  - Although phlebotomy is a common and widespread procedure, the medical literature
      provides limited information in terms of the documented complications of
      venipuncture. Documentation of phlebotomy-related nerve injuries is even more
      limited. The authors present a case report of a phlebotomy-induced lesion of the
      lateral antebrachial cutaneous nerve. According to our literature search, this is
      the first case in which electrodiagnostic studies were used to document
      venipuncture-related injury of the lateral antebrachial cutaneous nerve. Specific
      electrodiagnostic testing is used to definitively diagnose this rare injury and
      to track recovery. Electrodiagnostic testing can be helpful in evaluating cases
      of sensory disturbance after phlebotomy.

PMID- 11237279
TI  - Stroke care: a method for measuring compliance with AHCPR guidelines.
AB  - The purpose of this article is to describe a method for converting practice
      guidelines to measurement criteria. To evaluate the processes of care received by
      patients with stroke at 11 Veteran's Administration hospital sites, we developed
      a measurement system based on Agency for Health Care Policy and Research (AHCPR)
      Post-Stroke Rehabilitation Clinical Practice Guidelines. Guideline
      recommendations were used as the framework for identifying important dimensions
      of care, and for developing chart abstraction instruments for both the acute and
      postacute settings. Using a modified Delphi technique to solicit opinions from an
      expert panel, a method was developed for aggregation of item-level chart
      abstraction components to overall guideline compliance scores. The measurement
      system was shown to have good-to-excellent intrarater and interrater reliability
      at the item, dimension, and overall compliance score levels. Abstraction of a
      sample of 100 medical records demonstrated the ability of the instruments to
      detect variability in processes of post-stroke care. This study provides the
      foundation for future research, which will evaluate associations between
      processes of post-stroke care, as measured by this medical chart abstraction
      system, and patient outcomes. (All abstraction instruments, criteria, and scoring
      algorithms described in this article are available for download at
      http://www2.kumc.edu/coa.)

PMID- 11237280
TI  - Predictive role of the three-month CD4 cell count in the long-term clinical
      outcome of the first HAART regimen.
AB  - The aim was to evaluate whether the three-month CD4 cell counts are a reliable
      predictor of the long-term clinical outcome of HAART-treated patients, by an
      observational study of 585 patients initiating HAART in a clinical setting.
      Clinical failure was defined as the occurrence of new or recurrent AIDS-defining
      events or death, and was analysed by means of intention-to-treat, univariate and
      multivariate analyses. An adjusted Cox regression model was used to evaluate the
      effect of three-month CD4+ counts on clinical outcome. Clinical failure occurred
      in 65 patients (11.1%) during a median follow-up of 31 months (1-65) as a result
      of new AIDS-defining events (ADEs) in 48 patients, ADE recurrence in six, and
      death in 11. The mean (median; range) CD4+ counts were 156/microL (155; 4--529)
      in patients with and 362/microL (326; 18--1162) in patients without clinical
      failure (P < .0001). Moreover, the proportion of patients with mean CD4+ counts <
      200 microL was higher in those experiencing subsequent clinical failure (chi2:
      41.11; P< .00001). Multivariate analysis showed that baseline CD4+ counts < 50
      microL, HIV-RNA > 100,000 copies/mL and AIDS at baseline predicted failure; after
      adjusting for three-month CD4+ counts, this marker was the only one independently
      associated with clinical failure (HR 2.93; 95% Cl: 1.16--7.38). The three-month
      immunologic response is a reliable predictor of long-term clinical outcome.

PMID- 11237282
TI  - Can Langerhans cell UV injury and dendritic cell infection by immunodepressive
      viruses induce immunologic tolerance? Second part: immunologic tolerance in AIDS.
AB  - In the first part of the present editorial [1], we recalled experimental and
      clinical data demonstrating that 1) UV, via their effects on Langerhans cells,
      and 2) some so-called immunodepressive viruses, such as measles, lymphocytic
      choriomeningitis agents, and some animal retroviruses, via their action on
      dendritic cells, can induce tolerance in some conditions concerning immunologic
      parameters and/or the antigen(s). We present in this second part of the editorial
      a commentary on patients treated at the AIDS phase of HIV-1 infection for 3.5 to
      8 years. Among them, one has been submitted before and at the beginning of our
      treatment, for a psoriasis, to a PUVA irradiation, at the dose of 214.5 J
      (spectrum 230-320). We were present at the end of this irradiation to see the
      disappearance of his blood CD4 and of his suppressor T cells. Comparing his data
      with those of other patients of the cohort similarly treated, we have found
      arguments to consider that this UV-victim patient has presented for the 6 years
      of his clinically excellent survival and still presents manifestations of
      immunologic tolerance towards a fraction of his HIV-1 population.

PMID- 11237281
TI  - Autoantibodies to TNFalpha in HIV-1 infection: prospects for anti-cytokine
      vaccine therapy.
AB  - Tumor necrosis factor alpha (TNFalpha) is a proinflammatory cytokine principally
      involved in the activation of lymphocytes in response to viral infection.
      TNFalpha also stimulates the production of other cytokines, activates NK cells
      and potentiates cell death and/or lysis in certain models of viral infection.
      Although TNFalpha might be expected to be a protective component of an antiviral
      immune response, several lines of evidence suggest that TNFalpha and other
      virally-induced cytokines actually may contribute to the pathogenesis of HIV
      infection. Based on the activation of HIV replication in response to TNFalpha,
      HIV appears to have evolved to take advantage of host cytokine activation
      pathways. Antibodies to TNFalpha are present in the serum of normal individuals
      as well as in certain autoimmune disorders, and may modulate disease progression
      in the setting of HIV infection. We examined TNFalpha-specific antibodies in HIV
      infected non-progressors and healthy seronegatives; anti-TNFalpha antibody levels
      are significantly higher in GRIV seropositive slow/non-progressors (N = 120, mean
      = 0.24), compared to seronegative controls (N= 12, mean = 0.11). TNFalpha
      antibodies correlated positively with viral load, (P = 0.013, r = 0.282), and
      CD8+ cell count (P = 0.03, r = 0.258), and inversely with CD4+ cell count (P =
      0.003, r = - 0.246), percent CD4+ cells (P = 0.008, r = -0.306), and CD4 :CD8
      ratio (P = 0.033, r = - 0.251). TNFalpha antibodies also correlated positively
      with antibodies to peptides corresponding to the CD4 binding site of gp160 (P =
      0.001, r = 0.384), the CD4 identity region (P = 0.016, r = 0.29), the V3 loop (P
      = 0.005, r = 0.34), and the amino terminus of Tat (P = 0.001, r = 0.395);
      TNFalpha antibodies also correlated positively with antibodies to Nef protein (P
      = 0.008, r = 0.302). The production of anti-TNFalpha antibodies appears to be an
      adaptive response to HIV infection and suggests the potential utility of modified
      cytokine vaccines in the treatment of HIV infections as well as AIDS-related and
      unrelated autoimmune and CNS disorders.

PMID- 11237283
TI  - The susceptibility of macrophages to human immunodeficiency virus type 1 X4
      isolates depends on their activation state.
AB  - The demonstration that macrophages express CXCR4 has led to a reexamination of
      their susceptibility to human immunodeficiency (HIV)-1 X4 strains. Here, we
      examined the susceptibility to X4 HIV-1Lai of two previously characterized
      macrophage populations, obtained either as 1) adherent cells of five-day cultures
      of blood mononuclear cells (PBMC), followed by two days without nonadherent PBMC
      nor added cytokines (MDM-5d); or 2) as adherent cells recovered from one-hour
      incubation of PBMC, which were cultured for seven days with macrophage colony
      stimulating factor (MDM-MCSF). Exposing MDM-5d or MDM-MCSF to HIV-1Lai did not
      lead to productive infection, as indicated by a lack of (MDM-MCSF) or low (MDM
      5d) viral p24 levels in culture supernatants. However, MDM-5d vigorously
      transmitted HIV-1 Lai to autologous T lymphocytes, which was not the case of HIV
      1Lai-exposed MDM-MCSF. PCR analysis of the LTR RU5 region showed that X4 HIV-1Lai
      entered into both types of macrophages in the same manner as R5 HIV-1 BaL.
      However, in contrast to MDM-5d, there was a block of HIV-1 Lai retrotransciption
      in MDM-MCSF. Cytokine profile analysis of the two types of macrophages showed
      that TNF-alpha, IL-6 and RANTES levels were higher in MDM-5d than in MDM-MSCF,
      while the IL10 level was higher in MDM-MCSF, both producing similar IL16 levels.
      Altogether, these data indicate that HIV-1 X4 strains enter into macrophages but
      that their replication is blocked thereafter in a different manner according to
      the activation status of the cells.

PMID- 11237284
TI  - Pathogenesis of thyroid nodules: histological classification?
AB  - Thyroid nodule genesis may be considered as an amplification of thyroid
      heterogeneity due to genetic and/or epigenetic mechanisms. We classified the
      thyroid nodules in five types with distinct histological features: hyperplastic,
      neoplastic, colloid, cystic and thyroiditic nodules. Hyperplastic: Thyrocyte
      proliferation is under the control of TSH but several other paracrine and
      autocrine factors are secreted by follicular cells, the stromal apparatus and the
      lymphocytes, which are implicated in initiation and perpetuation of thyroid
      hyperplasia. Growth occurs mainly through TSHR, cAMP and PKA. Constitutive cAMP
      overproduction has been shown to be due to point mutation of the TSHR or Gs
      protein, producing overgrowth and hyperfunction. Neoplastic: Several activated
      oncogenes have been identified in thyroid malignancies. Oncogenes relevant to the
      thyroid carcinogenesis are: mutated TSHR and gsp (constitutive activation of
      cAMP); TRK (receptor for NGF); RET/PTC (phosphorylation of tyrosine kinase
      receptor)--an isoform of this oncogene is induced by radiation: ras (it encodes
      Gs proteins transducing mitogenic signals); and c-MET (receptor for hepatocyte
      growth factor). The evolution of a differentiated thyroid cancer towards an
      undifferentiated cancer is due to a mutation of a family of proteins (i.e., p53),
      which acts as a brake, preventing the genomic instability of cancer. It is
      suggested that a tumor initiates by RET or ras and possibly progresses--as a
      result of additional mutations and by p53 mutation--to anaplastic carcinoma.
      Colloid: Flattening of the epithelium and dilatation of follicles containing
      viscous material--made up by a concentrated solution of thyroglobulin (hTg)--is
      the characteristic of the colloid nodule. A defect of intraluminal reabsorption
      of hTg has been suggested but not proven. Experimentally, a load of iodine is
      able to change thyroid hyperplasia to a colloid feature; however, a load of
      iodine is rarely found in the clinical history of patients. A new clue to the
      pathogenesis comes from the finding that a relevant part of the colloid (10-20%)
      is made up of insoluble globules, where hTg is compacted in a polymeric form. It
      is suggested that stocking hTg into globules is defective in colloid nodules,
      leading to enormous enlargement of the follicle. Cystic: It is estimated that
      between 15 and 40% of thyroid nodules are partly or entirely cystic. The 'true
      cyst' is rare; most of the so-called cystic nodules are 'pseudocysts', which
      follow necrosis and colliquation. Necrosis issues as an imbalance between growth
      and the precisely regulated process of angiogenesis. More recently, the VEGF/VPF
      has been found to be at the origin of recent and recurrent cysts. Immunotoxic and
      apoptotic mechanisms have also been suggested. Chemical analysis of cystic fluid
      showed a 'denatured' and 'serum-like' pattern suggesting different mechanisms in
      the pathogenesis of the pseudocystic thyroid nodules. Thyroiditic: Nodular
      lymphocytic thyroiditis (NLT) includes two different entities: 1) lymphocyte
      thyroiditis growing as a nodule in a hyperplastic or normal gland, and 2)
      lymphocyte thyroiditis associated in the same nodule with other nodular diseases
      of the thyroid: papillary thyroid carcinoma and lymphoma have been found to be
      associated to chronic lymphocytic thyroiditis.

PMID- 11237285
TI  - Effect of ethyl esterification of phenolic acids on low-density lipoprotein
      oxidation.
AB  - Inhibition of copper-induced low-density lipoprotein (LDL) oxidation by phenolic
      acids and their ethyl esters was investigated. LDL oxidation was evaluated by the
      hydroperoxide concentration and the chromatographic pattern of apoprotein
      fractions after fast protein liquid chromatography (FPLC). Antiradical properties
      against 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical and 2,2'-azobis(2
      amidinopropane)dihydrochloride (AAPH) were also investigated, and lipophilicity
      determined by thin-layer chromatography. Caffeic acid at 5 microM and sinapic
      acid at 10 microM protected LDL against oxidation, inhibiting both hydroperoxide
      formation and the increase of apoprotein negative charge. Ferulic, gallic and p
      hydroxy cinnamic acids were ineffective. Ethyl esterification increased the
      lipophilicity of the five acids, and enhanced the antioxidant properties of
      caffeic, sinapic and ferulic acids. Ethyl caffeate was protective at 1 microM. In
      contrast, gallic and p-hydroxy cinnamic ethyl esters were ineffective. Our
      results indicate that ethyl esterification of phenolic acids increases
      lipophilicity of their ethyl esters and may enable a better incorporation into
      the lipid layer of the LDL particle and the exertion of their antioxidant effect
      in the true site of lipoperoxidation. However, increasing lipophilicity is not
      the only mechanism able to potentiate preexisting antioxidant properties of
      molecules, and probably other mechanisms are implicated.

PMID- 11237286
TI  - Modulation of beta2 integrin phenotype, adhesion, chemotaxis, and oxidative burst
      of neutrophils by cyclosporine.
AB  - Cyclosporine (CsA) is an immunosuppressive drug widely used to prevent allograft
      rejection, but its action on neutrophil function is not well known. Neutrophils
      play an important role in tissue damage during allograft rejection; chemotactic
      recruitment, adhesion to endothelial cells and oxidative burst of neutrophils are
      early events during allograft rejection. The aim of this work was to evaluate the
      effect of CsA on beta2 integrins' surface expression, adhesion to human umbilical
      endothelial cells (HUVECs), chemotaxis and oxidative burst by neutrophils. For
      any neutrophil function studied, data obtained from activated neutrophils exposed
      to CsA were compared with those derived from untreated controls. Results show
      that CsA does not block neutrophil chemotaxis and does not reduce surface
      expression of CD11 complex and HUVECs' adhesion at all concentrations tested (15,
      100 and 500 ng/mL) and at incubation times of 1, 2 and 4 h as compared to
      controls. On the other hand, the drug affects significantly the CD18 phenotype
      after two hours of treatment at the maximum concentration (500 ng/mL) (P < 0.05;
      ANOVA) and the oxidative burst after four hours (P < 0.01; ANOVA). This study
      provides evidence that in addition to the well-known CsA effects on lymphocyte
      functions, the drug affects some neutrophil functions with dose- and time
      dependent modalities.

PMID- 11237287
TI  - Residual HIV-1 RNA in blood plasma of patients taking suppressive highly active
      antiretroviral therapy.
AB  - Residual HIV-1 disease remains in the vast majority of patients treated with even
      the most intensive highly active antiretroviral therapy (HAART). There are at
      least two well-described molecular mechanisms for HIV-1 persistence in these
      patients. These include proviral latency in resting CD4+ T-cells, as well as
      'cryptic' residual viral replication. As well, potential sanctuary sites,
      including the brain and testes, may be important areas which will hinder HIV-1
      eradication attempts. It is not clear whether other sites of HIV-1 persistence,
      including tissue-bound infected monocytes/macrophages, may also be involved in
      residual HIV-1 disease during virally-suppressive HAART.

PMID- 11237288
TI  - Effect of liquid manure on the mole fraction of nitrous oxide evolved from soil
      containing nitrate.
AB  - The same emission factor is applied to fertiliser N and manure N when calculating
      national N2O inventories. Manures and fertilisers are often applied together to
      meet the N needs of the crop, but little is known about potential interactions
      leading to an increase in denitrification rate or a change in the composition of
      the end-products of denitrification. We used the 15N gas-flux method in a
      laboratory experiment to quantify the effect of liquid manure (LM) application on
      the fluxes of N2 and N2O when the soil contained fertiliser 15NO3-. LM increased
      the mole fraction of N2O from 0.5 to 0.85 in the first 12 h after application.
      More than 94% of the N2O was from the reduction of NO3-, probably due to aerobic
      nitrate respiration as well as respiratory denitrification.

PMID- 11237289
TI  - Nitrous oxide and dinitrogen emissions from soil under different water regimes
      and straw amendment.
AB  - In a laboratory study, soil amended with and without wheat straw (2.8 g kg(-1)
      soil) was incubated under 70% water holding capacity (WHC), continuously flooded
      and flooded/drained cycle conditions at 30 degrees C for 51 days. Dinitrogen and
      N2O evolution and ammonia volatilisation were measured during the incubation.
      Extractable NH4+-N and NO3--N were determined at the end of the incubation.
      Entrapped N2, N2O, and dissolved NH4+-N and NO3--N in drainage water were
      measured in the flooded/drained cycle treatment when the floodwater was drained.
      The results indicated that N loss through ammonia volatilisation was undetected
      in all treatments due to the low soil pH value (pHH2O= 5.87) and no air movement.
      The recovery of urea-15N as N2 was lowest in the continuously flooded treatments
      (0.75% and 0.96% with and without straw amendment, respectively), highest in the
      70% WHC treatments (5.65% and 4.41%, respectively), and intermediate in the
      flooded/drained cycle treatments (1.79% and 2.65%, respectively). The recovery of
      urea-15N as N2O was in the same order as that of N2, negligible in the
      continuously flooded treatments, 0.01% and 0.07% in the flooded/drained cycle
      treatments, and 1.29% and 2.23% in the 70% WHC treatments, respectively. Peak N2O
      evolution rates were observed after the floodwater was drained but no substantial
      evolution was found after the soil was reflooded following drained periods.
      However, peak N2 evolution rates were observed after the onset of both drainage
      and re-flooding. Considerable quantities of N2 but no detectable N2O were
      entrapped in the flooded soil.

PMID- 11237291
TI  - Use of precision agriculture technology to investigate spatial variability in
      nitrogen yields in cut grassland.
AB  - Spatial variability in N uptake and utilisation by swards within uniformly
      managed field units could be responsible for a significant proportion of the NH3,
      N2O, NO3- and NOx (NO and NO2) 'pollutants' generated by agriculture and released
      to the environment. An investigation was commenced, therefore, to quantify, map
      and explain the spatial variability in sward N yield in a 'large' silage field
      and to assess the potential for managing this variability using some of the
      latest precision agriculture technology. Sward dry matter (DM) and N yields were
      predicted from the results of plant tissue analyses using mathematical models.
      Sward N yields were found to vary greatly across the field seemingly because of
      differences in net soil N mineralisation, but the pattern of variability appeared
      to remain constant with time. Conventional soil analysis of a range of soil
      chemical and physical properties, however, failed to explain this variability. It
      was concluded that the N-yield distribution map might be used in place of soil
      analysis as the basis for varying the rates of N application to different parts
      of the field with the twin objectives of maximising fertiliser use efficiency and
      minimising N emissions to air and water.

PMID- 11237290
TI  - Factors affecting ammonia volatilisation from a rice-wheat rotation system.
AB  - Some of the major factors influencing ammonia volatilisation in a rice wheat
      rotation system were studied. A continuous airflow enclosure method was used to
      measure NH3 volatilisation in a field experiment at an agricultural college in
      Jiangsu Province. The five treatments comprised application rates of 0, 100, 200
      or 300 kg N ha(-1) as urea, per growing season with rice straw amendment when
      wheat was sown, and 200 kg N ha(-1) without rice straw amendment. There were
      three replicates in a randomised block design. Ammonia volatilisation was
      measured immediately after urea application in the three consecutive years 1995
      to 1997. The results show that N losses through NH3 volatilisation accounted for
      4-19% of N applied during the wheat growing season and for 5-11% during the rice
      growing season. Ammonia volatilisation was affected significantly by soil
      moisture and temperature before and after fertiliser application during the wheat
      growing season. The ratio of volatilised NH3-N to applied N after urea
      application during the rice growing season was as follows: top-dressing at the
      onset of tillering > top-dressing at the start of the booting stage > basal
      fertilization. The results also show that the amount of N lost through NH3
      volatilisation increased with increasing N application rate, but the ratio to
      applied N was not affected significantly by N application rate. Amendment with
      rice straw had no significant effect on NH3 volatilisation.

PMID- 11237292
TI  - Changes in soil organic carbon storage under grassland as evidenced by changes in
      sulphur input-output budgets.
AB  - Information about temporal changes in soil organic carbon (C) pools may be
      obtained indirectly from changes in input-output budgets of organically combined
      nutrients such as sulphur (S). Sulphur budgets were therefore evaluated for
      Northern Ireland (NI) for the period 1940-1990, inclusive. These budgets
      indicated that the land or soil had acted first as a sink but then as a source
      for S, and that reserves of soil S built up between 1940 and 1965 were totally
      depleted by the mid-1980s. Pooled data from six long-term soil-monitoring sites
      on undisturbed grassland suggested that negative S budgets from the late-1970s
      onwards had been due to the net mineralization of soil organic matter and thus
      were indicative of net losses of organic C from surface soil horizons. There was
      some evidence that the decline in rainfall and fertiliser S inputs from the mid
      1960s may have precipitated the breakdown of soil organic matter.

PMID- 11237293
TI  - The role of arbuscular mycorrhizal fungi in the transfer of nutrients between
      white clover and perennial ryegrass.
AB  - A glasshouse experiment was conducted in which 15N was used as a tracer applied
      as (15NH4)2SO4 to donor plants of white clover and perennial ryegrass. Nitrogen
      transfer via hyphae of arbuscular mycorrhizal fungi (AMF) or by other routes was
      studied by separating the root systems of the two plant species, as donors and
      receivers, when growing in the same pot, with selective mesh barriers of varying
      pore sizes in the presence and absence of AMF. Inoculation with AMF increased DM
      production and nitrogen (N) yield of clover plants. Transfer of 15N occurred
      between white clover and grass plants but was independent of AMF. Pore size of
      the mesh barriers controlled the degree of 15N enrichment in the grass,
      suggesting that transfer was mediated by mass flow and/or diffusion. Additional
      experiments showed that grass roots could pass through pores of 60-microm
      diameter, and hyphal links could not be detected by autoradiography, thus
      supporting the conclusions of the tracer experiment.

PMID- 11237294
TI  - Phosphorus quantity-intensity relationships and agronomic measures of P in
      surface layers of soil from a long-term slurry experiment.
AB  - Soils from a long-term slurry experiment established in 1970 at Hillsborough,
      Northern Ireland, were used in the experiment. The site has a clay loam soil
      overlying Silurian shale. Seven treatments were used with three replicate plots
      per treatment. Control plots were treated with mineral fertiliser supplying 200
      kg N, 32 kg P and 160 kg K ha(-1) yr(-1). Slurry treatment plots were in two
      blocks and treated with either pig or cow slurry supplied at 50, 100 or 200 m3
      ha(-1) yr(-1). Agronomic measures of P determined on 10-cm soil cores were
      compared with measured P quantity/intensity (Q/I) parameters from fitted sorption
      and desorption isotherms. Phosphorus affinity constant was found to be
      significantly and negatively correlated with P loading of soils. Desorption rate
      coefficient also increased significantly with increase in P loading from slurry,
      although there was no significant difference between slurry types (cow vs. pig).
      In contrast, while agronomic measures of P (water-soluble P, Olsen P, calcium
      chloride-extractable P, degree of P saturation (DPS)) also correlated
      significantly with P loading and total P (TP) in the soils, there was a
      separation and significant differences between the cow and pig slurry treatment
      blocks, with the former being much lower. Phosphorus inputs to pig slurry treated
      plots were much higher than to equivalent cow slurry plots over the first 15
      years of the study but declined sharply over the most recent 10 years to more or
      less par. Conventional measures of agronomic P such as Olsen P and DPS, measure
      only P accumulation over the longer term and indicated only the higher content of
      P accumulating in soil of pig slurry treatments. Risk of P loss estimated by Q/I
      parameters appeared to show very similar behaviour between the two slurry types
      in line with more recent manurial additions but in contradiction of P
      accumulation statistics.

PMID- 11237295
TI  - Agronomic measures of P, Q/I parameters and lysimeter-collectable P in subsurface
      soil horizons of a long-term slurry experiment.
AB  - Soils from a long-term slurry experiment established in 1970 at Hillsborough,
      Northern Ireland, were used in the experiment. The site has a clay loam soil
      overlying Silurian shale. Seven treatments were used with three replicate plots
      per treatment under the following manurial regimes: (1) mineral fertiliser
      supplying 200 kg N, 32 kg P and 160 kg K ha(-1) yr(-1); (2)-(4) pig slurry
      applied at 50, 100 or 200 m3 ha(-1) yr(-1); (5)-(7) cow slurry applied at 50, 100
      or 200 m3 ha(-1) yr(-1). Agronomic measures of P determined on subsurface layers
      down to 90 cm were compared with sorption isotherm data and rates of desorption.
      Adsorption isotherms were fitted using a standard Langmuir model. Data were
      compared with soluble (molybdate-reactive) P levels in soil water collected at 35
      and 90 cm using PTFE suction cup lysimeters. Agronomically available P was
      concentrated in the top 30 cm of soil in all treatments. The accumulation of P in
      surface layers of the plots was significantly greater in the pig slurry
      treatments compared to the cow slurry, reflecting the history of P amendments.
      Nevertheless, over a period of a year, molybdate-reactive phosphorus (MRP)
      concentrations in lysimeter collections was consistently higher at 35 cm depth in
      the highest cow slurry treatment (7) compared to the equivalent pig slurry
      treatment (4). Either the movement of soluble P down the profile is facilitated
      by the higher organic content of cow slurry or P movement is not directly related
      to P accumulation in the soils. In addition, it is hypothesised that P movement
      down the soil profile depends upon two separate mechanisms. First, a 'break'
      point above which the accumulated P in the surface horizons is less strongly held
      and therefore amenable to dissolution and movement down the profile. Second, a
      mechanism by which some solute P from the surface horizons can travel rapidly
      through horizons of low P status to greater depth in the soil, i.e., by
      preferential flow.

PMID- 11237296
TI  - Soil solution dynamics of Cu and Zn in a Cu- and Zn-polluted soil as influenced
      by gamma-irradiation and Cu-Zn interaction.
AB  - A pot experiment was conducted to study soil solution dynamics of Cu and Zn in a
      Cu/Zn-polluted soil as influenced by gamma-irradiation and Cu-Zn interaction. A
      slightly acid sandy loam was amended with Cu and Zn (as nitrates) either singly
      or in combination (100 mg Cu and 150 mg Zn kg(-1) soil) and was then gamma
      irradiated (10 kGy). Unamended and unirradiated controls were included, and
      spring barley (Hordeum vulgare L. cv. Forrester) was grown for 50 days. Soil
      solution samples obtained using soil moisture samplers immediately before
      transplantation and every ten days thereafter were used directly for
      determination of Cu, Zn, pH and absorbance at 360 nm (A360). Cu and Zn
      concentrations in the solution of metal-polluted soil changed with time and were
      affected by gamma-irradiation and metal interaction. gamma-Irradiation raised
      soil solution Cu substantially but generally decreased soil solution Zn. These
      trends were consistent with increased dissolved organic matter (A360) and
      solution pH after gamma-irradiation. Combined addition of Cu and Zn usually gave
      higher soil solution concentrations of Cu or Zn compared with single addition of
      Cu or Zn in gamma-irradiated and non-irradiated soils, indicating an interaction
      between Cu and Zn. Cu would have been organically complexed and consequently
      maintained a relatively high concentration in the soil solution under higher pH
      conditions. Zn tends to occur mainly as free ion forms in the soil solution and
      is therefore sensitive to changes in pH. The extent to which gamma-irradiation
      and metal interaction affected solubility and bioavailability of Cu and Zn was a
      function of time during plant growth. Studies on soil solution metal dynamics
      provide very useful information for understanding metal mobility and
      bioavailability.

PMID- 11237297
TI  - A modified glass bead compartment cultivation system for studies on nutrient and
      trace metal uptake by arbuscular mycorrhiza.
AB  - A modified glass bead compartment cultivation system is described in which glass
      beads continue to be used in the hyphal compartment but are replaced by coarse
      river sand in the compartments for host plant roots and mycorrhizal hyphae.
      Arbuscular mycorrhizal (AM) associations were established using two host plant
      species, maize (Zea mays L.) and red clover (Trifolium pratense L.) and two AM
      fungi, Glomus mosseae and G. versiforme. When the standard and modified
      cultivation systems were compared, the new method yielded much more fungal tissue
      in the hyphal compartment. Using G. versiforme as the fungal symbiont, up to 30
      mg of fungal dry matter (DM) was recovered from the hyphal compartment of
      mycorrhizal maize and about 6 mg from red clover. Multi-element analysis was
      conducted on samples of host plant roots and shoots and on harvested fungal
      biomass. Concentrations of P, Cu and Zn were much higher in the fungal biomass
      than in the roots or shoots of the host plants but fungal concentrations of K,
      Ca, Mg, Fe and Mn were similar to or lower than those in the plants. There were
      also significant differences in nutrient concentrations between the two AM fungi
      and these may be related to differences in their proportions of extraradical
      mycelium to spores. The high affinity of the fungal mycelium for Zn was very
      striking and is discussed in relation to the potential use of arbuscular
      mycorrhiza in the phytoremediation of Zn-polluted soils.

PMID- 11237298
TI  - Uptake of Zn by arbuscular mycorrhizal white clover from Zn-contaminated soil.
AB  - A randomised block glasshouse pot experiment compared the growth and Zn uptake of
      mycorrhizal and nonmycorrhizal white clover plants grown in a sterile soil/sand
      mixture containing 25 mg Zn kg(-1) to which five application rates of Zn (as
      ZnSO4) from 0 to 400 mg kg(-1) were made. Two mycorrhizal inocula infected roots
      from the field and from clover trap cultures, were compared. Mycorrhizal
      infection (ranging from 33% to 46% of total root length) and Zn application had
      little effect on plant growth. Increasing Zn application rate led to increased
      uptake of Zn in roots and shoots (especially roots), but the increases were
      significantly greater in non-mycorrhizal controls than in mycorrhizal treatments.
      In contrast, P uptake was higher in mycorrhizal than in non-mycorrhizal plants.
      Plants that received trap culture inoculum had significantly lower Zn uptake than
      those that received field inoculum. The results indicate that mycorrhizal
      infection may have exerted some protective effect against plant Zn accumulation
      at the range of soil Zn concentrations studied and may have immobilised Zn in or
      near the roots to some extent. However, this mycorrhizal effect cannot be
      explained simply by tissue dilution, hyphal sequestration or root immobilisation
      of Zn.

PMID- 11237299
TI  - Changes in soil solution Zn and pH and uptake of Zn by arbuscular mycorrhizal red
      clover in Zn-contaminated soil.
AB  - Red clover plants inoculated with Glomus mosseae were grown in a sterile pasture
      soil containing 50 mg Zn kg(-1) in 'Plexiglas' (acrylic) containers with nylon
      net partitions (30 microm mesh) designed to separate the soil into a central root
      zone and two outer zones for hyphal growth with no root penetration. Two porous
      plastic soil moisture samplers were installed in each pot, one in the root
      compartment and the other in one of the hyphal compartments. The soil in the
      outer compartments was amended with one of the four application rates of Zn (as
      ZnSO4) ranging from 0 to 1000 mg kg(-1). Non-mycorrhizal controls were included,
      and there were five replicates of each treatment in a randomised block in a
      glasshouse. Uninoculated plants received supplementary P to avoid yield
      limitation due to low soil P status. Plants grew in the central compartment for
      nine weeks. Soil moisture samples were collected 4, 24 and 62 days after sowing
      to monitor changes in the Zn concentration and pH of the soil solution. At
      harvest, the mean mycorrhizal infection rate of inoculated plants ranged from 29%
      to 34% of total root length and was little affected by Zn application. Root and
      shoot yields were not affected by mycorrhizal infection. Plant Zn concentration
      and uptake were lower in mycorrhizal plants than non-mycorrhizal controls, and
      this effect was more pronounced with increasing Zn application rate to the soil.
      Soil solution Zn concentrations were lower and pH values were higher in
      mycorrhizal treatments than non-mycorrhizal controls and the mycorrhiza effect
      was more pronounced at higher Zn application rates. The protective effect of
      mycorrhiza against plant Zn uptake may have been associated with changes in Zn
      solubility mediated by changes in the soil solution pH, or by immobilisation of
      Zn in the extraradical mycelium.

PMID- 11237300
TI  - Surface water phosphorus dynamics in rice fields receiving fertiliser and manure
      phosphorus.
AB  - A long-term randomised block field experiment was established in 1997 to study
      the dynamics of total P and dissolved P in the surface waters of rice fields
      receiving two application rates of fertiliser P and one rate of combined
      fertiliser and manure P. Preliminary results from the first two crops show that
      concentrations of both total P and dissolved P in the surface waters increased
      significantly following P application, especially during the first 2 weeks after
      application. P concentrations subsequently declined sharply within about 10 days,
      then declined steadily and remained almost constant from about 1 month after
      application. The initial increase in P concentration of surface waters was higher
      with increasing rate of fertiliser P, and the P concentration at the highest
      fertiliser rate peaked within about 1 week of application. The elevated P
      concentrations following fertiliser P application declined more rapidly than
      those following the combined application of fertiliser and manure P. When
      fertiliser and manure P were applied together, about 7 days later the surface
      water P concentrations were significantly higher than when the same rate of P (or
      double) was applied as fertiliser only. Disturbance of the surface soil by hand
      harrowing further increased the P concentrations in surface waters, with a
      subsequent decline to a steady value after about 1 week. Application of P
      fertiliser to the high P status soil in this experiment gave no crop yield
      response and may have increased the risk of pollution of adjacent surface waters
      through drainage from heavy rainfall events during the rice growing season.
      Therefore, fertiliser P should not be applied to such soils. If, however,
      fertiliser or manure P is applied, the application should be made during the dry
      winter to reduce P losses. Manure should be applied with particular care because
      of the higher risk of P losses to surface water arising from the relatively long
      period of high P concentrations in surface waters and the potential for greater
      release of P to field surface waters from the soil. Hand harrowing should also be
      avoided during wet weather to protect water quality.

PMID- 11237301
TI  - The importance of catchment and lake processes in the phosphorus budget of a
      large lake.
AB  - Total phosphorus (P) river inputs and lake concentrations for the Neagh system in
      Northern Ireland are compared from the period 1974-1997. The main routes of P
      transfer between the lake water and the sediment are settlement of abiotic
      particles and planktonic diatoms, summer sediment release and re-sedimentation in
      the last months of the year. The annual river loading to the lake varied between
      0.7 and 1.8 g P m(-2), and sediment release can be as much as 1.4 g P m(-2). A
      simple model evaluated the effect of sediment-water exchanges on the phosphorus
      available for spring phytoplankton growth. It showed that re-sedimentation of
      released P and washout over the winter greatly mitigated its effect. Correlation
      analysis demonstrated that the very large summer releases of sediment P were not
      related directly to the spring inputs from diatom settlement. No long-term trends
      in P release were seen.

PMID- 11237302
TI  - Evaluation of phosphorus bioavailability in sediments of three contrasting lakes
      in China and the UK.
AB  - The bioavailability of phosphorus (P) in sediments from West Lake and Lake Tai
      (China) and Lough Erne (Northern Ireland) was evaluated using total P (TP), water
      soluble P (WSP), readily desorbable P (RDP), algal available P (AAP) and Olsen-P.
      The results indicated that the TP content, the amounts of phosphorus extracted by
      each method and their proportions to TP varied widely between sediments of the
      three lakes. TP and chemical extractable phosphorus in the sediments of Lough
      Erne were considerably higher than those of the two lakes in China. Although TP
      in the West Lake sediments was similar to that of Lake Tai, the extractable
      phosphorus data suggested that the bioavailability of P in West Lake sediments
      was higher than that in sediments from Lake Tai. Nevertheless, the rank order of
      extraction efficiency was the same in all lakes and the amount extracted was in
      the sequence AAP > Olsen-P > WSP > RDP. There was a good correlation between
      extracted and TP in all the methods examined.

PMID- 11237303
TI  - Canadian consensus conference on dementia: two years later.

PMID- 11237304
TI  - The use of medications for cognitive enhancement.
AB  - OBJECTIVE: To provide Canadian physicians and allied health care professionals
      with the evidence they need to help them make treatment decisions in the
      management of patients with Alzheimer's disease or other dementias. OPTIONS: The
      full range and quality of diagnostic and therapeutic modalities available to
      Canadian physicians for the management of dementia. OUTCOMES: Improvement in the
      treatment of dementias, leading to reduced suffering, increased functional
      capacity and decreased economic burden. EVIDENCE AND VALUES: The creation of
      these evidence-based consensus statements involved literature reviews of the
      subject by the authors; comparison of alternative clinical pathways and
      description of the methods whereby published data were analyzed; definition of
      the level of evidence for data in each case; evaluation and revision in a
      conference setting (involving primary care physicians, neurologists,
      psychiatrists, geriatricians, psychologists, consumers and other interested
      parties); insertion of tables showing key variables and data from various studies
      and tables of data with recommendations; and reassessment by all authors.
      BENEFITS, HARMS, AND COSTS: A rational plan for the therapy of dementias is
      likely to lead to substantial benefits in both human and economic terms.
      RECOMMENDATIONS: Treatment decisions should be made taking into account the
      severity or stage of the disease, the availability of caregivers, the presence of
      disease affecting other bodily systems and the ability of the subject to pay the
      cost of the medications. Donepezil is considered to have positive effects upon
      certain tests of neuropsychological function and may produce some improvement in
      Alzheimer's disease of mild to moderate severity as measured by rating scales.
      Its ability to improve quality of life remains uncertain. No other drug
      treatments (apart from symptomatic therapies) are at present approved for the
      treatment of Alzheimer's disease*. VALIDATION: These recommendations were created
      by a writing committee, evaluated and revised at a consensus conference and
      further reviewed and revised by the writing committee prior to publication.

PMID- 11237305
TI  - Recommendations of the Canadian Consensus Conference on Dementia--dissemination,
      implementation, and evaluation of impact.
AB  - BACKGROUND: Subsequent to the development of consensus statements on a clinical
      topic, it is vital to establish a plan for dissemination, implementation and
      evaluation of impact. Consensus statements can be used for both guiding
      continuing medical education (CME) and producing clinical practice guidelines
      (CPGs). Insufficient attention to dissemination can lead to a failure to change
      physician behaviour and improve patient outcomes. METHODS: A plan to disseminate
      the conclusions of the Canadian Consensus Conference on Dementia (CCCD) was
      developed. This plan was based on a literature review of CME and CPGs. A Medline
      search was performed on the dissemination and evaluation of the 1989 Canadian
      Consensus Conference on the Assessment of Dementia (CCCAD) and other published
      guides for physicians on dementia care. CCCD dissemination that has occurred to
      date (June, 2000) was reviewed in this paper. RESULTS: Lectures and unsolicited
      printed material are weak forms of CME. Small-group interactive CME that provides
      practice opportunities appears to be the most effective way to change physician
      behaviour. The ability of CPGs to change physician behaviour is uncertain. It
      appears that inadequate attention has been placed on CPG dissemination and
      implementation. The CCCAD had a modest impact on clinical practice in Canada.
      While dissemination of the conclusions of the CCCD has taken place, evaluation of
      the impact of the CCCD has yet to be done. Local initiatives utilizing the
      conclusions of the CCCD are on-going. CONCLUSIONS: Further work is needed on how
      to optimize the impact of consensus statements and CPGs. While dissemination of
      the CCCD has occurred, it is currently unknown whether it has led to any change
      in physician practices.

PMID- 11237306
TI  - Brief review: rivastigmine, a second cholinesterase inhibitor.

PMID- 11237307
TI  - Diagnosis, classification and natural history of degenerative dementias.
AB  - The release of the first approved medications for the treatment of Alzheimer's
      disease in Canada has highlighted the renewed need and importance of diagnostic
      accuracy and understanding of the spectrum of the dementias. The epidemiological
      scope of the problem of dementia in Canada including risk factors, caregiving
      patterns and costs of care have been well-characterized through the Canadian
      Study of Health and Aging (CSHA 1991-1996) with some of the key findings reviewed
      here. Beyond Alzheimer's disease the phenotypes and genotypes of the other
      degenerative dementias have been emerging with proposed operational diagnostic
      criteria that should facilitate their recognition in clinical practice. This
      paper reviews the clinical phenotypes of the most common causes of dementia with
      a proposed classification scheme and with discussion of their relevance from a
      differential treatment standpoint. This paper served as a background document for
      the working group of the Consensus Conference on Dementia (C3D) in February 1998
      and has been revised subsequently for this publication.

PMID- 11237308
TI  - Assessment of suspected dementia.
AB  - At the Second Canadian Consensus Conference on Dementia (CCCD) (February, 1998),
      a group of neurologists, geriatricians, and psychiatrists met to consider
      guidelines for evaluation of dementia in Canada. This review paper formed a
      background paper for their discussion of dementia diagnosis. These experts from
      across the country concluded that diagnosis of suspected dementia cases continued
      to rest on skilled clinical assessment. Mental status exam, preferably in some
      quantifiable form, has become an essential part of the assessment. Selected
      laboratory tests are advisable in all cases (CBC, TSH, electrolytes, calcium, and
      glucose), but the CCCD continued to advise that CT scanning was mandatory only in
      selected cases where clinical findings pointed to another possibility besides
      Alzheimer's disease. The growing list of other diagnostic measures with potential
      usefulness in diagnosis of Alzheimer's disease or dementia in general was
      reviewed, but the evidence was judged as insufficient to support routine use of
      these tests by physicians. As new treatments for Alzheimer's disease become
      available, neurologists face new diagnostic challenges--differentiating Mild
      Cognitive Impairment, Frontotemporal dementias and Mixed dementias, and Lewy Body
      Dementia. Guidelines to aid in differential diagnosis are presented.

PMID- 11237309
TI  - The recognition, assessment and management of dementing disorders: conclusions
      from the Canadian Consensus Conference on Dementia.
AB  - OBJECTIVE: i) To develop evidence based consensus statements on which to build
      clinical practice guidelines for primary care physicians towards the recognition,
      assessment and management of dementing disorders; ii) to disseminate and evaluate
      the impact of these statements and guidelines built on these statements. OPTIONS:
      Structured approach to assessment, including recommended laboratory tests,
      choices for neuroimaging and referral; management of complications (especially
      behaviour problems and depression) and use of cognitive enhancing agents.
      POTENTIAL OUTCOMES: Consistent and improved clinical care of persons with
      dementia; cost containment by more selective use of laboratory investigations,
      neuroimaging and referrals; appropriate use of cognitive enhancing agents.
      EVIDENCE: Authors of each background paper were entrusted to: perform a
      literature search, discover additional relevant material including references
      cited in retrieved articles; consult with other experts in the field and then
      synthesize information. Standard rules of evidence were applied. Based upon this
      evidence, consensus statements were developed by a group of experts, guided by a
      steering committee of eight individuals from the areas of Neurology, Geriatric
      Medicine, Psychiatry, Family Medicine, Preventive Health Care and Health Care
      Systems. VALUES: Recommendations have been developed with particular attention to
      the context of primary care and are intended to support family physicians in
      their ongoing assessment and care of patients with dementia. BENEFITS, HARMS AND
      COSTS: Potential for improved clinical care of individuals with dementia. A
      dissemination and evaluation strategy will attempt to measure the impact of the
      recommendations. RECOMMENDATIONS: See text. VALIDATION: Four other sets of
      consensus statements and/or guidelines have been published recently. These
      recommendations are generally congruent with our own consensus statements. The
      consensus statements have been endorsed by relevant bodies in Canada.

PMID- 11237310
TI  - Screening for cognitive impairment and dementia in the elderly.
AB  - OBJECTIVE: To review the evidence available to support or refute the
      recommendation to screen for cognitive impairment (cognitive deficits which do
      not affect daily function) and dementia in primary care. DATA SOURCES: Medline
      search using terms listed at the end of this article; consultation with experts
      in the field; review of other published recommendations. STUDY SELECTION: There
      were no articles which described a randomized controlled trial of screening
      versus no screening. Studies were therefore chosen which aided in the definition;
      natural history; interventions and outcomes including possible negative effects.
      DATA SYNTHESIS: No systematic synthesis was performed. Background papers were
      circulated to a panel of experts prior to the Canadian Consensus Conference on
      Dementia and conclusions endorsed by consensus. CONCLUSIONS: 1. There is
      insufficient evidence to recommend for or against screening for cognitive
      impairment or dementia. (C); 2. Memory complaints should be evaluated and the
      individual followed to assess progression. (B); 3. When caregivers or informants
      describe cognitive decline in an individual, these observations should be taken
      very seriously; cognitive assessment and careful follow-up are indicated. (A)
      (See Appendix).

PMID- 11237311
TI  - Genetic counselling and genetic screening for Alzheimer's disease and other
      dementias.
AB  - Genetic and nongenetic factors have been identified to have roles in the etiology
      of dementia. Etiologic heterogeneity and genetic heterogeneity are recognized,
      especially for Alzheimer's disease which is the most common form of dementia.
      Asymptomatic individuals are increasingly requesting genetic services such as
      genetic counselling, predictive testing and screening for genetic risk factors.
      This paper provides an overview of the current knowledge about genetic
      counselling and genetic screening for dementia as well as guidelines for the
      physician.

PMID- 11237312
TI  - Preventing dementia.
AB  - Primary prevention will become increasingly important as dementia prevalence
      increases and effective retardive therapies are developed. To date, only one
      randomized controlled trial (involving treatment of systolic hypertension) has
      demonstrated that the incidence of dementia can be reduced. Physicians should
      remain alert to possible secondary causes of dementia and correct these whenever
      possible. Primary and secondary prevention of stroke should reduce dementia
      related to cerebrovascular disease either directly or as a comorbid factor in
      Alzheimer's disease (AD). Epidemiological studies have revealed a number of risk
      factors for AD including genetic mutation, susceptibility genes, positive family
      history, Down's syndrome, age, sex, years of education, head trauma and
      neurotoxins. In case-control studies non-steroidal anti-inflammatory medication
      and estrogen replacement therapy appear to decrease the relative risk of
      developing AD. Further research to develop and test preventative therapies in AD
      and other dementias should be strongly encouraged.

PMID- 11237313
TI  - Disclosing a diagnosis of Alzheimer's disease: patient and family experiences.
AB  - BACKGROUND: Informing patients and families about the diagnosis of Alzheimer's
      disease (AD) is a complex ethical and practical issue. This qualitative study
      explores the psychosocial impact of disclosing a diagnosis of AD on patients and
      family members. METHODS: This study identified 14 patients and their accompanying
      family members undergoing a multidisciplinary assessment for dementia at an
      outpatient clinic for AD and related disorders. Of the group, three patients had
      probable AD and five had possible AD as per NINCDS-ADRDA criteria. Six patients
      were not demented as per DSM IIIR criteria. Disclosure of diagnosis occurred, in
      a family conference, within six to eight weeks of the assessment. Data collection
      methods included observation of the assessment and the family conference as well
      as in-depth home interviews with family members and with each patient whenever
      feasible. The interviews were transcribed verbatim and coded for recurrent
      themes. RESULTS: A total of 40 individuals across 14 families participated in
      this study. Only two families chose not to have the patient attend the family
      conference. The disclosure of a diagnosis of probable AD brought on an experience
      of relief in three families, marking the end of a lengthy period of confusion
      about the nature of memory problems. Patients diagnosed with possible AD and
      their families interpreted how indicative the diagnosis was of the presence of
      the disease with varying degrees of certainty depending on pre-assessment beliefs
      about the cause of memory problems. In the group diagnosed as not demented, four
      patients had complaints of forgetfulness likely related to minor depression. The
      disclosure of a diagnosis of no dementia did not produce the anticipated relief.
      Two patients continued to believe their memory problems were caused by the early
      onset of AD or some other "organic" problem. INTERPRETATION: This study reveals
      that disclosure of the diagnosis of AD to patients and family members is
      generally beneficial but that there are variations in the understanding of the
      diagnostic information, particularly in instances where the assessment results
      are ambiguous.

PMID- 11237314
TI  - Dementia caregiving: the role of the primary care physician.
AB  - BACKGROUND: Family and friends play an important role in caring for individuals
      with dementia living in the community. In preparation for the Canadian Consensus
      Conference on Dementia held in Montreal, Canada in February 1998, the subject of
      dementia caregiving was reviewed in order to provide primary care physicians with
      some guidelines for their practice. The review was updated in June 2000 in
      preparation for this article. METHOD: Pertinent English-language publications and
      resources from the Alzheimer Society of Canada were reviewed from 1985 onwards.
      Findings related to the consequences of caregiving, services for caregivers and
      recommendations regarding the role of the primary care physician were reviewed.
      FINDINGS: Dementia caregivers experience many positive and negative consequences
      of caregiving. Some comprehensive services for caregivers have been shown to
      delay institutionalization and reduce negative consequences of caregiving. The
      primary care physician has a role to play in working with families and should
      address the following issues: 1) education about dementia; 2) psychological
      support for caregivers; 3) assistance mobilizing caregiver social support
      networks. CONCLUSION: Primary care physicians have an important role to play in
      acknowledging and supporting the caregiving provided by family and friends to
      individuals with dementia.

PMID- 11237315
TI  - Cultural aspects of dementia.
AB  - This paper critically reviews current knowledge regarding culture and dementia in
      order to identify unanswered questions in the field. Medline was searched from
      1993-2000. One hundred nine articles were identified, of which 59 were critically
      reviewed, augmented by additional references from experts and by books. Limited
      research evidence was identified in four areas: 1) the recognition of dementia
      across cultures 2) cultural specificity of screening tools 3) identification of
      differences in risk factors, incidence, onset and prevalence across culture 4)
      culturally related issues in decision making about management. Implications for
      research and practice are described.

PMID- 11237316
TI  - Depressive syndromes in dementia.
AB  - BACKGROUND: Depressive syndromes in dementia are common, treatment is challenging
      and controlled intervention studies are small in number. The goal of this paper
      is to review known information about the etiology, epidemiology and treatment of
      these syndromes, as summarized at the recent Canadian Consensus Conference on
      Dementia. METHODS: A number of Medline searches were performed (most recently
      updated in October 2000) using the subject categories dementia and depression, or
      apathy or emotional lability and other relevant articles were also reviewed. The
      background article was edited and amended at the Consensus Conference on
      Dementia. Final recommendations appearing in the summary article by Patterson et
      al were accepted by the group consensus process. Clinical discussion and
      informational updates were added for the current text by the authors. RESULTS:
      Depressive syndromes, ranging in severity from isolated symptoms to full
      depressive disorders, increase in dementia. While clear-cut depressive disorder
      is increased in this population, sub-syndromal disorders are even more common and
      cause considerable distress. Antidepressant treatment may improve the quality of
      life in depressed, demented people, although it is less successful than in those
      without cognitive impairment and carries more risk of iatrogenic effects.
      CONCLUSIONS: Physicians should be alert to the presence of depressive syndromes
      in dementia. Depressive illness should be treated and, when necessary, referral
      should be made to an appropriate specialist. Treatment must minimize iatrogenic
      effects. Although there is some support for treatment of syndromes that do not
      meet criteria for depressive disorder or dysthymia, the first line of
      intervention in these situations should involve nonpharmacological approaches.

PMID- 11237317
TI  - Recommendations for the management of behavioral and psychological symptoms of
      dementia.
AB  - BACKGROUND: The behavioral and psychological symptoms of dementia (BPSD) are
      common, serious problems that impair the quality of life for both patient and
      caregiver. In order to provide recommendations based upon the best available
      evidence, a qualitative literature review was performed. METHODS: A search of the
      English language medical literature published between 1966 and 2000 was
      performed. The quality of the studies was assessed by considering the subjects,
      trial design, analysis and results. Final recommendations were based upon the
      quality of available evidence. RESULTS: The management of BPSD begins with a
      thorough assessment to search for underlying causes of behaviour change.
      Concomitant medical illness should be treated and sensory impairment ameliorated.
      Nonpharmacological approaches should be instituted prior to medication use. These
      interventions include music, light, changes in level of stimulation and specific
      behavioral techniques. Antipsychotics are the best studied pharmacological
      intervention for agitation and aggression and have demonstrated modest but
      consistent efficacy. Antidepressants such as trazodone and selective serotonin re
      uptake inhibitors, as well as anticonvulsants such as carbamazepine and valproic
      acid have also demonstrated efficacy. Benzodiazepines can be used for short-term
      treatment as p.r.n. agents when necessary. Pharmacotherapy must be monitored
      closely for both effectiveness and side effects, with consideration of medication
      withdrawal when appropriate. CONCLUSION: The management of BPSD can significantly
      improve the quality of life for the patient and caregiver. Their assessment and
      management are essential components of the treatment of dementia.

PMID- 11237318
TI  - DNA affinity chromatography of transcription factors.

PMID- 11237319
TI  - Use of the tape stripping technique for directly quantifying esterase activities
      in human stratum corneum.
AB  - The enzymes secreted in the intercellular spaces of stratum corneum (SC), the
      outermost layer of the epidermis, are thought to be involved in normal
      desquamation and skin barrier function. Their activity can barely be measured due
      to the difficulty in isolating enough biological material. Human SC layers were
      obtained from the forearm of healthy volunteers by the tape stripping technique.
      Assays for esterase activities were carried out in specially designed plates
      which contained the SC blotted on tape strips, using various fluorescent
      methylumbelliferone acyl esters as substrates. Triacylglycerol hydrolase
      activities were also studied by this method. By using radiolabeled triolein and
      fluorescent 4-methylumbelliferyl 7-oleate as substrates, true lipase activities
      could be detected and quantitated in SC at pH 5.5 and 7.5. These activities were
      shown to be strongly inhibited by tetrahydrolipstatin while this was not the case
      with 4-methylumbelliferyl 7-heptanoate. The method described here combines the
      painless tape stripping technique with a sensitive plate assay analysis. Since
      the whole process needs little manipulation, this method can permit rapid
      quantitation of multiple enzyme activities from a single strip. Therefore, it
      will permit the study of the involvement of enzyme activities in epidermis aging
      and skin pathologies.

PMID- 11237320
TI  - Recombinant phycobiliproteins. Recombinant C-phycocyanins equipped with affinity
      tags, oligomerization, and biospecific recognition domains.
AB  - A family of specific cloning vectors was constructed to express in the
      cyanobacterium Anabaena sp. PCC7120 recombinant C-phycocyanin subunits with one
      or more different tags, including the 6xHis tag, oligomerization domains, and the
      streptavidin-binding Strep2 tag. Such tagged alpha or beta subunits of Anabaena
      sp. PCC7120 C-phycocyanin formed stoichiometric complexes in vivo with
      appropriate wild-type subunits to give constructs with the appropriate
      oligomerization state and normal posttranslational modifications and with
      spectroscopic properties very similar to those of unmodified phycocyanin. All of
      these constructs were incorporated in vivo into the rod substructures of the
      light-harvesting complex, the phycobilisome. The C-terminal 114-residue portion
      of the Anabaena sp. PCC7120 biotin carboxyl carrier protein (BCCP114) was cloned
      and overexpressed and was biotinylated up to 20% in Escherichia coli and 40% in
      wild-type Anabaena sp. His-tagged phycocyanin beta--BCCP114 constructs expressed
      in Anabaena sp. were >30% biotinylated. In such recombinant phycocyanins equipped
      with stable trimerization domains, >75% of the fusion protein was specifically
      bound to streptavidin- or avidin-coated beads. Thus, the methods described here
      achieve in vivo production of stable oligomeric phycobiliprotein constructs
      equipped with affinity purification tags and biospecific recognition domains
      usable as fluorescent labels without further chemical manipulation.

PMID- 11237321
TI  - Isolation of Escherichia coli mRNA and comparison of expression using mRNA and
      total RNA on DNA microarrays.
AB  - Bacterial messenger RNA (mRNA) is not coherently polyadenylated, whereas mRNA of
      Eukarya can be separated from stable RNAs by virtue of polyadenylated 3'-termini.
      We have developed a method to isolate Escherichia coli mRNA by polyadenylating it
      in crude cell extracts with E. coli poly(A) polymerase I and purifying it by
      oligo(dT) chromatography. Differences in lacZRNA levels were similar with
      purified mRNA and total RNA in dot blot hydridizations for cultures grown with or
      without gratuitous induction of the lactose operon. More broadly, changes in gene
      expression upon induction were similar when cDNAs primed from mRNA or total RNA
      with random hexanucleotides were hydridized to DNA microarrays for the E. coli
      genome. Comparable signal intensities were obtained with only 1% as much
      oligo(dT)-purified mRNA as total RNA, and hence in vitro poly(A) tailing appears
      to be selective for mRNA. These and additional studies of genome-wide expression
      with DNA microarrays provide evidence that in vitro poly(A) tailing works
      universally for E. coli mRNAs.

PMID- 11237322
TI  - Miniaturization of a hepatitis C virus RNA polymerase assay using a -102 degrees
      C cooled CCD camera-based imaging system.
AB  - Innovations in detection technologies have allowed us to develop a novel assay in
      1536-well plate format and assess the advantages of screen miniaturization
      compared with conventional high-throughput compound screening in 96- or 384-well
      plates. An HCV RNA polymerase assay has been miniaturized in 1536-well plates by
      using a new detection technology known as LEADseeker homogeneous imaging system.
      It uses a -102 degrees C cooled charge-coupled device (CCD) camera and newly
      designed scintillation proximity microparticles. The miniaturized assay used
      europium-doped streptavidin-coated yttrium oxide (YO(x)) or polystyrene (PS)
      microspheres to capture biotin-labeled [(3)H]RNA product transcripts. Beads in
      proximity to the radioisotope convert the emitted beta(-) particles into photons
      having wavelengths in the red region of the visible spectrum, optimal for
      detection by the CCD camera. Because the camera collects light from all wells of
      the plate simultaneously, 1536-well plates are imaged as rapidly as 384-well
      plates, on the order of 10 min per plate. The assay has a signal to background of
      approximately 20-fold, satisfactory for high-throughput robotics screening. The
      enzyme kinetics and potency of a known inhibitor were similar to those obtained
      from the conventional assay using scintillation proximity assay (SPA) beads and a
      scintillation plate counter. Furthermore, the newly developed microbeads
      (emitting at 610 to 620 nm) are less prone to quenching effects caused by yellow
      colored compounds, than conventional SPA beads or scintillation fluid (emitting
      at 400 to 480 nm region). Thus, the LEADseeker imaging system is a useful new
      tool for miniaturization of assays for high-throughput screening.

PMID- 11237323
TI  - Mag-indo1 affinity for Ca(2+), compartmentalization and binding to proteins: the
      challenge of measuring Mg(2+) concentrations in living cells.
AB  - A physicochemical study of the Mag-indo1 binding to Ca(2+) in solution showed
      that: (i) the characteristic fluorescence spectra of Ca(2+)-bound and Mg(2+)
      bound Mag-indo1 are identical; (ii) two successive equilibria occur for
      increasing Ca(2+) concentrations; and (iii) the value of the dissociation
      constant of the first one, as determined by using a probe dilution protocol,
      amounts to 780 nM. In order to investigate the fluorescence level of Mag-indo1
      trapped in cell organelles, fluorescence spectra of Mag-indo1-loaded fibroblasts
      were recorded before and after a digitonin permeabilization. Their resolution
      into cation-bound, protein-bound, and free Mag-indo1 characteristic spectra
      allowed measurement of the fluorescence intensities of these species. The
      intensities emitted from whole cells were compared to those emitted from
      organelles (assumed to be endoplasmic reticulum according to a DiOC(6) loading).
      The cation-bound Mag-indo1 fluorescence resulted partially (20 to 50%) from the
      cytosol for 30% of the cells, and totally from compartments for 70% of the cells.
      We found a concentration value of 500 nM for compartmentalized Ca(2+) and
      concluded that the Mag-indo1 binding to Ca(2+) is likely to affect drastically
      the Mg(2+) concentration measurements in cells. Moreover, we showed that the
      amount variation of protein-bound Mag-indo1 also affects Mg(2+) measurements when
      using the two-wavelength ratio method.

PMID- 11237324
TI  - Controlled immobilization of DNA molecules using chemical modification of mica
      surfaces for atomic force microscopy: characterization in air.
AB  - Immobilization of biomolecules on surfaces while keeping the maximum
      conformational flexibility of the molecules is one of the most important
      techniques for atomic force microscopy imaging. We have developed two methods of
      controlling adsorption of DNA molecules on mica surfaces. The first method is the
      use of a mica surface modified with diluted 3-aminopropyltriethoxysilane (APS).
      Here we named this a "diluted APS-treated mica (AP-mica)" technique. The second
      method is the use of a mica surface modified with mixed self-assembled monolayers
      of organosilanes. In both of the techniques, the number of DNA molecules
      immobilized on a mica surface was controlled. Further, a conformational change of
      circular DNA, from a supercoiled to a relaxed form was observed for the molecules
      immobilized on a diluted AP-mica surface, when 254-nm UV light was irradiated.
      This observation demonstrated that flexibility of circular DNA molecules was kept
      on a diluted AP-mica surface.

PMID- 11237325
TI  - Measurement of succinylcholine concentration in human plasma by electrospray
      tandem mass spectrometry.
AB  - An electrospray mass spectrometric method for the quantification of the
      depolarizing neuromuscular blocking agent succinylcholine (SUX) is described. An
      extraction method compatible with direct infusion inlet was developed and leads
      to an analysis cycle time of 7--8 min instead of 25 min that would be required
      for HPLC inlet. SUX was extracted from human plasma on C1 solid-phase cartridges
      and was analyzed using positive ion electrospray tandem mass spectrometry (ESI
      MS/MS). SUX plasma concentrations were determined by a stable isotope dilution
      assay using hexadeuterosuccinylcholine diiodide (SUXd6) as the internal standard.
      The calibration curve was prepared using the ratio of intensities of the major
      product ions in the collision-induced dissociation spectrum for known
      concentration ratios of SUX and SUXd6 in plasma. Calibration curves for the
      quantification were linear from 25 to 4000 ng/ml. For intraday precision, CV were
      < or =6% and accuracy ranged from 98 to 103%. For the interday precision, CV were
      < or =10% and accuracy ranged from 90 to 102%. This method is specific,
      sensitive, reproducible, and practical in a clinical setting.

PMID- 11237326
TI  - An amperometric cellobiose dehydrogenase-based biosensor can be used for
      measurement of cellulase activity.
AB  - The hemoflavoenzyme cellobiose dehydrogenase (CDH, EC 1.1.99.18) from
      Phanerochaete chrysosporium has been used in an amperometric redox polymer-based
      biosensor. Used in conjugation with a FIA system this biosensor can replace
      colorimetric assays for measuring cellobiose liberated from cellulose in a series
      of cellulase-containing samples. The biosensor gave the same result as the
      Somogyi-Nelson method in a less time-consuming and laborious manner. The two
      methods showed about the same precision.

PMID- 11237327
TI  - Determination of reduced, protein-unbound, and total concentrations of N-acetyl-L
      cysteine and L-cysteine in rat plasma by postcolumn ligand substitution high
      performance liquid chromatography.
AB  - A high-performance liquid chromatographic assay was developed for the
      quantitative determination of the sulfur-containing amino acids N-acetyl-L
      cysteine (NAC) and L-cysteine (Cys) in rat plasma. The thiols were separated by
      reverse-phase ion-pair chromatography, and the column eluent was continuously
      mixed with an iodoplatinate-containing solution. The substitution of sulfur of
      the thiol compound with iodide was quantitatively determined by measuring changes
      in the absorption at 500 nm. The low-molecular-weight disulfides and mixed
      disulfide conjugates of thiols with proteins were entirely reduced to the
      original reduced compounds by dithiothreitol. By reducing these two types of
      disulfides separately during sample pretreatment, the reduced, protein-unbound,
      and total thiol concentrations could also be determined. Validation testing was
      performed, and no problems were encountered. The limit of detection was
      approximately 20 pmol of thiol on the column. The present method was used to
      measure the plasma concentrations of NAC and Cys in the rat after a bolus
      intravenous administration of NAC, focusing on disulfide formation. The binding
      of NAC to protein through mixed disulfide formation proceeds in a time-dependent
      and reversible manner. Moreover, this "stable" covalent binding might limit total
      drug elimination, while the unbound NAC is rapidly eliminated. Consequently, the
      analytical method described in this study is very useful for the determination of
      plasma NAC and Cys, including disulfide conjugates derived from them.

PMID- 11237328
TI  - Selection-marker-free modification of the murine beta-casein gene using a lox2272
      [correction of lox2722] site.
AB  - Gene targeting and site-specific recombination strategies allow the precise
      modification of the eukaryotic genome. Many of the recombination strategies
      currently used, however, will introduce a selection marker gene at the modified
      site. DNA sequences of prokaryotic origin like vector sequences, selection
      marker, and reporter genes have been shown to markedly influence the regulation
      of the modified genomic loci. In order to avoid the insertion of excess
      sequences, a biphasic recombination strategy involving homologous recombination
      and Cre-recombinase-mediated cassette exchange (RMCE) was devised and used to
      insert a foreign gene into the beta-casein gene in murine embryonic stem cells.
      The incompatibility of the heterospecific lox sites used for the recombinase
      mediated cassette exchange was found to be critical for the success of the
      strategy. The frequently used mutant site lox511, which differs from the natural
      loxP site by a single point mutation, proved unsuitable for this approach. A
      mutant lox site carrying two point mutations, however, was highly effective and
      90% of the selected cell clones carried the desired modification. This biphasic
      recombination strategy allows for the efficient and precise modification of gene
      loci without the concomitant introduction of a selectable marker gene.

PMID- 11237329
TI  - Expression of recombinant extracellular domain of the type II transforming growth
      factor-beta receptor: utilization in a modified enzyme-linked immunoabsorbent
      assay to screen TGF-beta agonists and antagonists.
AB  - TGF-beta is a ubiquitous protein that exhibits a broad spectrum of biological
      activity. The prokaryotic expression and purification of the extracellular domain
      of the type II TGF-beta receptor (T beta R-II-ED), without the need for fusion
      protein cleavage and refolding, is described. The recombinant T beta R-II-ED
      fusion protein bound commercially available TGF-beta 1 and displayed an affinity
      of 11.1 nM. In a modified ELISA, receptor binding to TGF-beta1 was inhibited by
      TGF-beta 3. The technique lends itself to high-throughput screening of
      combinatorial libraries for the identification of TGF-beta agonists and
      antagonists and this, in turn, may have important therapeutic implications.

PMID- 11237330
TI  - Iron(II) phthalocyanine-modified carbon-paste electrode for potentiometric
      detection of ascorbic acid.
AB  - A chemically modified electrode constructed by incorporating iron(II)
      phthalocyanine [Fe(II)Pc] into carbon-paste matrix was used as a sensitive
      potentiometric sensor for detection of ascorbic acid. The resulting electrode
      exhibits catalytic properties for the electrooxidation of ascorbic acid, and
      lowers the overpotential for the oxidation of this compound. The faster rate of
      electron transfer results in a near-Nernstian behavior of the modified electrode,
      and makes it a suitable potentiometric sensor for detection of ascorbic acid. A
      linear response in concentration range from 10(-6) to 10(-2) M (0.18--1800 microg
      ml(-1)) was obtained with a detection limit of 5 x 10(-7) M for the
      potentiometric detection of ascorbic acid. The modified electrode was used for
      the determination of ascorbic acid in vitamin preparations. The recovery was 97.2
      -102.4% for the vitamin added to the preparations with a relative standard
      deviation of less than 5%. The modified electrode exhibited a fast response time
      (<10 s),had good stability, and had an extended lifetime.

PMID- 11237331
TI  - Simultaneous detection of NOS-3 protein expression and nitric oxide production
      using a flow cytometer.
AB  - Nitric oxide (NO) is involved in the regulation of SMC proliferation during
      intimal hyperplasia as has been shown by the inhibitory effect on intimal
      hyperplasia of adenovirus-mediated ceNOS overexpression in injured arteries in
      pig. Good assays to quantify the NO-producing enzymes, i.e., NO synthases (NOS),
      are essential to analyze the mechanism of action of NO in this process. We have
      developed novel flow cytometric assays for the simultaneous detection of NOS-3
      protein, using NOS-3 specific antibodies, and NO production using 4,5
      diaminofluorescein-diacetate (DAF-2/DA). The presence of NOS-3 protein and NO
      production is demonstrated on human A549 and HepG2 cells infected with a NOS-3
      adenovirus (Ad.NOS-3). A comparative study showed that the flow cytometric assays
      are equally sensitive as Western blot analysis, the citrulline assay, or the
      Sievers assay. On human endothelial and SMC, NOS-3 protein and NO production were
      simultaneously detected with the assays, both under basal conditions and after
      Ad.NOS-3transduction. Simultaneous analysis of NOS-3 protein and NO production,
      made possible by the here-described novel flow cytometric assays, is of
      significant value to those investigating NOS-3 and NO.

PMID- 11237332
TI  - Formation and efficacy of vancomycin group glycopeptide antibiotic stereoisomers
      studied by capillary electrophoresis and bioaffinity mass spectrometry.
AB  - The conformational stability of vancomycin group antibiotics (i.e., vancomycin
      and avoparcin) in aqueous solution has been studied. These complex glycopeptide
      antibiotics contain many chiral centers allowing the potential formation of
      stereoisomers. Using capillary electrophoresis these stereoisomers could be
      separated and detected by UV and/or mass spectrometry. Fresh aqueous samples of
      both vancomycin and avoparcin already contained a plethora of stereoisomers.
      Thermal degradation of the antibiotics was studied as well. For vancomycin
      thermal degradation led primarily to the formation of CDP-I and aglycons. In the
      case of avoparcin thermal degradation led mainly to the interconversion between
      stereoisomers. These antibiotic stereoisomers may exhibit different antibacterial
      efficacy. Solution-phase association constants of fresh and heated samples of
      these antibiotics and their bacterial cell wall mimicking receptors were
      determined by bioaffinity mass spectrometry and revealed that the heated samples
      exhibited, in general, a lower affinity. Minimum inhibitory concentrations
      (Micrococcus flavus) were determined and confirmed the decrease in antibacterial
      efficacy upon heating.

PMID- 11237333
TI  - Electrospray ionization mass spectrometry analysis of lysophospholipids in human
      ascitic fluids: comparison of the lysophospholipid contents in malignant vs
      nonmalignant ascitic fluids.
AB  - Lysophospholipids (lyso-PLs), including various glycerol-based and sphingosine
      based lysophospholipids, play important roles in many biochemical, physiological,
      and pathological processes. The classical methods to analyze these lipids involve
      gas chromatography and/or high-performance liquid chromatography, which are time
      consuming, cumbersome, and sometimes inaccurate due to the incomplete separation
      of closely related lipid species. We now describe the quantitative analysis of
      lyso-PLs in ascites samples from patients with ovarian cancer using electrospray
      ionization spectrometry. Three new classes of lyso-PL molecules are detected:
      alkyl-LPA, alkenyl-LPA, and methylated lysophosphatidylethanolamine. Importantly,
      the following lysophospholipid species are significantly increased in ascites
      from patients with ovarian cancer, compared to patients with nonmalignant
      diseases (e.g., liver failure): LPA (including acyl-, alkyl-, and alkenyl-LPA
      species), lysophosphatidylinositol, and sphingosylphosphorylcholine.
      Lysophosphorylcholine contents are also significantly different among ascitic
      fluids from the two groups of patients. However, the total phosphate content in
      ascites samples from patients with ovarian cancer is not significantly different
      compared to that from patients with nonmalignant disease.

PMID- 11237334
TI  - Experimental and theoretical microdialysis studies of in situ metabolism.
AB  - Microdialysis sampling was performed to monitor localized metabolism in vivo and
      in vitro. A mathematical model that accounts for analyte mass transport during
      microdialysis sampling was used to predict metabolite concentrations in the
      microdialysis probe during localized metabolism experiments. The model predicts
      that metabolite concentrations obtained in the microdialysis probe are a function
      of different experimental parameters including membrane length, perfusion fluid
      flow rate, and sample diffusive and kinetic properties. Different microdialysis
      experimental parameters including membrane length and perfusion fluid flow rate
      were varied to affect substrate extraction efficiency (E(d)), or loss to the
      sample matrix, in vivo and in vitro. Local hepatic metabolism was studied in vivo
      in male Sprague-Dawley rats by infusing acetaminophen through the microdialysis
      probe. Acetaminophen sulfate concentrations increased linearly with respect to
      acetaminophen E(d) in contrast to modeling predictions. Xanthine oxidase was used
      as an in vitro model of localized metabolism. In vitro experimental results
      partially matched modeling predictions for 10-mm probes. These results suggest
      that monitoring local metabolism using microdialysis sampling is feasible. It is
      important to consider system parameters such as dialysis flow rate, membrane
      length, and sample properties because these factors will affect analyte
      concentrations obtained during local metabolism experiments.

PMID- 11237335
TI  - Mass-spectrometry-linked screening of protein fractions for enzymatic activities-
      a tool for functional genomics.
AB  - A simple and rapid strategy is described to screen protein fractions for defined
      enzymatic activity. A protein fraction from a porcine kidney extract was
      immobilized by covalent coupling to activated affinity beads. The immobilized
      proteins were incubated with probes specific for different enzyme activities. The
      reaction products were analyzed by matrix-assisted laser desorption/ionization
      (MALDI)-mass spectrometry. The MALDI spectra indicate the presence of 5'
      nucleotidase, phosphatase, kinase, glutathione reductase, and renin activities in
      the kidney protein extract. Furthermore, the method can be used to screen for
      inhibitors of enzymatic reactions. The method is adaptable to high-throughput
      sample handling and automated mass spectrometric analysis and therefore suited
      for functional genomics.

PMID- 11237336
TI  - Pseudomonas aeruginosa protease IV enzyme assays and comparison to other
      Pseudomonas proteases.
AB  - Pseudomonas aeruginosa secretes multiple proteases that have been implicated as
      virulence factors and the detection of each specific enzyme can be difficult to
      determine. Unlike the three Pseudomonas enzymes that have been well characterized
      (elastase A, elastase B, and alkaline protease), the activity of protease IV in
      multiple assays has yet to be described. This study defines new assays for
      Pseudomonas proteases and compares protease IV activity to the activities of
      elastase A, elastase B, and alkaline protease. Six in vitro assays were studied:
      zymography, elastin congo red assay, staphylolytic assay, colorimetric peptide
      assay, solid-phase colorimetric peptide assay, and poly-l-lysine degradation.
      Casein zymography distinguished protease IV from elastase B and alkaline
      protease, and gelatin zymography differentiated all four proteases. The elastin
      congo red assay detected mainly elastase B while the staphylolytic assay was
      specific for elastase A. Protease IV activity was assayed specifically by the
      colorimetric assay and two new assays, the solid-phase colorimetric assay and
      degradation of poly-L-lysine in the presence of EDTA. Alkaline protease could be
      specifically assayed by poly-L-lysine degradation in the presence of N-alpha-p
      tosyl-L-lysine chloromethyl ketone. The results identified three specific assays
      for protease IV, a new assay specific for alkaline protease, and showed that
      protease IV has a distinct enzymatic specificity relative to the three other
      Pseudomonas proteases.

PMID- 11237337
TI  - A fluorescence-based homogeneous assay for measuring activity of UDP-3-O-(R-3
      hydroxymyristoyl)-N-acetylglucosamine deacetylase.
AB  - UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) is one of
      the key enzymes of bacterial lipid A biosynthesis, catalyzing the removal of the
      N-acetyl group of UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine. The lpxC
      gene is essential in Gram-negative bacteria but absent from mammalian genomes,
      making it an attractive target for antibacterial drug discovery. Current assay
      methods for LpxC are not suitable for high throughput screening, since they
      require multiple product separation steps and the use of radioactively labeled
      material that is difficult to prepare. A homogeneous fluorescence-based assay was
      developed that uses UDP-3-O-(N-hexyl-propionamide)-N-acetylglucosamine as a
      surrogate substrate. This surrogate can be prepared from commercially available
      UDP-GlcNAc by enzymatic conversion to UDP-MurNAc, which is then chemically
      coupled to n-hexylamine. Following the LpxC reaction, the free amine of the
      deacetylation product can be derivatized by fluorescamine, thus generating a
      fluorescent signal. This surrogate substrate has a K(m) of 367 microM and k(cat)
      of 0.36 s(-1), compared to 2 microM and 1.5 s(-1) for the natural substrate.
      Since no separation is needed, the assay is easily adaptable to high throughput
      screening. IC(50)s of LpxC inhibitors determined using this assay method is
      similar to those measured by traditional method with the natural substrate.

PMID- 11237338
TI  - Improved oligonucleotide sequencing by alkaline phosphatase and exonuclease
      digestions with mass spectrometry.
AB  - The combination of exonuclease digestion and mass spectrometry has been widely
      used for sequencing oligonucleotides. During an exonuclease digestion, rapid
      buildup in the concentration of nucleotides produces strong signal of nucleotide
      cluster ions in electrospray ionization-mass spectrometry, especially for
      oligonucleotides with greater than 25 bases. This leads to poor signal/noise
      ratio in the reconstructed molecular weight spectra of late digestion products
      due to artifact peaks from nucleotide cluster ions. Here we report a procedure
      that eliminates the effect of the cluster ions. In this method, alkaline
      phosphatase is added with snake venom phosphodiesterase to the oligonucleotide
      solution to convert the interfering nucleotides into noninterfering nucleosides,
      and the collision-induced dissociation spectrum of the dimeric oligonucleotide at
      the end of the digestion is obtained to determine the sequence of the last two
      bases at the 5'-terminus of the oligonucleotide. With this approach, the
      signal/noise ratio of the reconstructed molecular weight spectrum is greatly
      improved for relatively large oligonucleotides, and only a single digestion is
      needed for sequencing.

PMID- 11237339
TI  - Chromatographic quantification of argpyrimidine, a methylglyoxal-derived product
      in tissue proteins: comparison with pentosidine.
AB  - Methylglyoxal (MG), an alpha-dicarbonyl compound, can be produced in vivo by
      several metabolic pathways and the Maillard reaction. It reacts rapidly with
      proteins to form advanced glycation end products or AGEs. We previously isolated
      and characterized a blue fluorescent product of the reaction between MG and
      arginine, which we named argpyrimidine. We found that argpyrimidine was stable to
      acid hydrolysis, which allowed us to hydrolyze tissue proteins with 6 N HCl and
      quantify argpyrimidine by high-performance liquid chromatography. Here we report
      argpyrimidine concentrations in human lens and serum proteins as determined by
      HPLC. We have also measured pentosidine, a fluorescent AGE derived from pentose
      sugars, and compared the concentrations of pentosidine and argpyrimidine. We
      found two- to threefold higher argpyrimidine concentrations in diabetic serum
      proteins than in nondiabetic controls (9.3 +/- 6.7 vs 4.4 +/- 3.4 pmol/mg). We
      found a significant correlation (P = 0.0001) between serum protein argpyrimidine
      and glycosylated hemoglobin. Argpyrimidine concentrations were approximately
      seven times greater in brunescent cataractous lenses than in aged noncataractous
      lenses. Pentosidine concentrations in serum and lens proteins were much lower
      than argpyrimidine concentrations; in general, argpyrimidine levels were 10--25
      times higher than pentosidine. Results from our study confirm that MG-mediated
      arginine modifications occur in vivo and provide a method for assessing protein
      arginine modification by MG in aging and diabetes.

PMID- 11237340
TI  - Enzymatic determination of homocysteine in cell extracts.
AB  - Determination of homocysteine levels in cells and serum is important because high
      homocysteine is a risk factor for cardiovascular disease. The currently used
      methods for homocysteine analysis either are time consuming or rely on the use of
      expensive equipment. Described in this study is an enzymatic assay that
      determines levels of homocysteine in multiple samples in less than 30 min at
      levels from 5 to 50 pmol using only a spectrophotometer. The reproducibility of
      the assay is consistent with the other methods currently used. A second assay,
      that is about 5-fold more sensitive, follows the enzymatic catalyzed solvent
      exchange of protons on glycine, which requires a scintillation counter. Both the
      spectrophotometric and the radiometric methods are based on the conversion of 5
      methyltetrahydrofolate to tetrahydrofolate by methionine synthase. The
      tetrahydrofolate is formed in stoichiometric amounts to the homocysteine in the
      sample. In the spectrophotometric method the tetrahydrofolate is used at
      catalytic levels by three enzymes to form a metabolic cycle that generates NADPH
      from NADP(+). In the radiometric assay tetrahydrofolate is required for the
      enzymatic exchange of the pro 2S proton of glycine with solvent. L-Cysteine, at
      levels more than 30-fold higher than the upper level of homocysteine used in
      these assays, does not give any measurable response.

PMID- 11237342
TI  - Synthesis of allicin and purification by solid-phase extraction.

PMID- 11237341
TI  - Monofunctional derivatives of coproporphyrins for phosphorescent labeling of
      proteins and binding assays.
AB  - p-Isothiocyanatophenyl derivatives of Pt(II)- and Pd(II)-coproporphyrin I are
      described as stable monofunctional reagents which enable simple covalent labeling
      of proteins and other biomolecules under mild conditions in aqueous solutions.
      Labeling procedure was optimized for antibodies, avidin, and neutravidin.
      Photophysical properties of resulting conjugates important for their use in
      binding assays based on time-resolved phosphorescence detection were studied. The
      functional activity and long-term storage stability of antibody conjugates were
      assessed in comparison with unmodified proteins. The new labels and their
      conjugates were evaluated in the solid-phase immunoassays using commercial time
      resolved phosphorescence readers Victor(2) and Arcus-1230 (Wallac). Potential
      applications of these reagents in in vitro diagnostics are discussed.

PMID- 11237343
TI  - A high-throughput microtiter plate-based calcium assay for the study of protease
      activated receptor 2 activation.

PMID- 11237344
TI  - An electrochemiluminescent method for the detection of beta-lactamases in
      microorganisms.

PMID- 11237345
TI  - Spectrophotometric analysis for determining the average number of poly(ethylene)
      glycol molecules on PEGylated proteins utilizing a protein digestion step.

PMID- 11237346
TI  - Impact of moods and social context on eating behavior.
AB  - The relationship of moods and social context to energy and nutrient intakes was
      examined to ascertain if these variables interact or function independently. The
      subjects were 78 predominantly white, obese women participating in weight-loss
      studies. Mean age was 36.7 (SD=7.6) and mean Body Mass Index was 32.1 (SD=3.6).
      Subjects completed 2-week baseline food diaries recording everything they ate,
      including moods and people present during the meals. Meals eaten in positive and
      negative moods were significantly larger than meals eaten in a neutral mood.
      Meals eaten with other people were significantly larger than meals eaten alone.
      There were no significant moods by social context interactions for total energy
      intake. Moods and social context functioned additively to increase the risk of
      over-eating. Macro nutrient analysis revealed only a main effect for social
      context. Percentage of calories from fat and protein were greater, whereas the
      percentage of carbohydrate was less in social context meals compared to meals
      eaten alone. Clinicians should conduct a functional analysis to assess exposure
      to the frequency and types of risky situations. Teaching people to cope more
      effectively with social situations and moods may increase the efficacy of weight
      loss and maintenance programs.

PMID- 11237347
TI  - Exercise-induced nausea is exaggerated by eating.
AB  - This study was conducted to determine whether and under what circumstances
      exercise causes nausea. Twelve healthy volunteers (20-37 years), including six
      athletes, participated in the study. Subjects were studied on seven occasions.
      Each subject performed low and high-intensity exercise without eating,
      immediately after eating a beef patty and 60 min after eating. Besides these
      exercise experiments, effect of meal on nausea was studied in each subject for
      180 min without exercise. Exercise was done on a bicycle ergometer for 60 min at
      40-50% maximal heart rate reserve and 20 min at 70-80% maximal heart rate
      reserve. Subjects were tested for nausea by visual analogue scales. Both low and
      high-intensity exercise caused nausea. Scores for nausea were greater during
      exercise at fasting state and immediately after eating than those without
      exercise (p<0.05 during low-intensity exercise, and p<0.01 during high-intensity
      exercise). Immediately after eating, scores for nausea were greater during high
      intensity exercise than during low-intensity exercise (p<0.05). During high
      intensity exercise, scores for nausea were greater immediately after eating than
      without eating (p<0.05). There were no differences in ratings for nausea between
      the sexes in any of the experimental conditions. Training did not decrease
      exercise-induced nausea. In conclusion, exercise causes nausea, the severity of
      which is related to exercise intensity and food intake, but not sex differences
      nor physical training.

PMID- 11237348
TI  - Influences on meat consumption in Australia.
AB  - In a study of influences on meat consumption, over 700 South Australians answered
      questions on frequency of meat consumption, beliefs about meat and nutrition,
      perceived difficulties with and benefits of vegetarian diets, personal values,
      number of vegetarian significant others, use in and trust of
      health/nutrition/food information sources, and demography. Perceived difficulties
      with vegetarian diets, the number of vegetarian significant others and beliefs
      about meat were important predictors of meat consumption. There were differences
      between men and women and members of different age groups, which should be taken
      into account when attempts are made to influence meat consumption. For example,
      health promotion campaigns that focus on whether or not meat is necessary in the
      diet may influence meat consumption, but would be most successful if directed
      predominantly at older people and men. In contrast, the meat consumption of women
      and younger people was strongly associated with more specific concerns about lack
      of iron and protein in the vegetarian diet. Some of the difficulties people find
      with vegetarian diets will also apply to plant-based diets generally, and such
      diets are becoming more widely acknowledged as providing health benefits.
      Therefore, the findings have important implications for public health.

PMID- 11237349
TI  - Mood and carbohydrate cravings.
AB  - The relationship between mood and carbohydrate cravings, and the possible role of
      gender in these associations, was investigated in a sample of 113 males and 138
      female college students. Participants completed a Cravings Questionnaire and
      several mood inventories (profile of mood states, Beck Depression Inventory, and
      the Vitality Inventory) in groups of 25. Individuals classifying themselves as
      "carbohydrate cravers" reported foods rich in carbohydrates, and "protein
      cravers" reported protein-rich foods as being the ones they most strongly craved.
      Carbohydrate cravers reported feeling distressed prior to their cravings and
      satisfied, happy/good and relaxed following carbohydrate consumption. Protein
      cravers reported feeling anxious or hungry prior to their cravings and happy,
      normal, bored, and energetic following protein-rich food consumption. A non
      significant correlation existed between "protein" cravers' ratings of craving
      intensity and mood, but a significant positive correlation existed between
      "carbohydrate" cravers' ratings of craving intensity and almost all mood scales
      assessed for both male and female "carbohydrate" cravers. The correlation between
      craving intensity and mood existed predominately with individuals who craved
      sweet carbohydrate-rich foods.

PMID- 11237350
TI  - The effect of weight-loss dieting on cognitive performance and psychological well
      being in overweight women.
AB  - This study investigated the effect of a weight reduction diet on cognitive
      performance and psychological well-being among overweight women. A total of 42
      women undertook a 12-week weight reduction diet while 21 women maintained their
      usual diet and exercise habits for 12 weeks. All women completed
      neuropsychologcial tests of speed of information processing, executive function,
      working memory, immediate and delayed recall and recognition, and verbal ability.
      They also completed measures of weight locus of control, dieting beliefs, self
      esteem, mood and dysfunctional attitudes, before and after the 12-week interval.
      Being on the diet had a minimal impact on cognitive performance and a positive
      effect on emotional eating, feelings of depression and dysfunctional attitudes. A
      sense of control over weight and eating behaviour increased among the dieters,
      but an internal locus of control was negatively related to self-esteem.

PMID- 11237351
TI  - Appetite is not influenced by a unique milk peptide: caseinomacropeptide (CMP).
AB  - The milk protein, caseinomacropeptide (CMP), is a predominant breakdown product
      of casein in the human stomach, and may aid in the regulation of food intake.
      Using a human feeding study design, this project assessed the effects of CMP on
      satiety and satiation by measuring the amount of food consumed at meal times and
      through subjective motivation to eat questionnaires. The following beverage
      treatments were prepared: 0.4% CMP solution, 2.0% CMP solution, vehicle alone,
      and water containing colorant and clouding agent. Twenty male and 32 female
      adults were enrolled into the study using a Latin Square randomization. Treatment
      beverages and ad libitum lunches were consumed on four separate occasions at the
      Study Center. After lunch, subjects left the Study Center, and completed a
      standardized questionnaire every hour throughout the afternoon and evening to
      assess hunger and stomach fullness, and kept track of all food and beverages
      consumed. Under these experimental conditions, CMP had no effect on energy intake
      or weight of food consumed at lunch or for the remainder of the day. CMP also had
      no effect on subjective indicators of satiety. Intake of CMP before a midday meal
      has no effect on regulation of food intake over a short-term period.

PMID- 11237352
TI  - Self-presentational conflict in social eating situations: a normative
      perspective.
AB  - This study explored the degree to which people adhere to norms for "appropriate"
      eating behavior in social situations. Of particular interest was how people
      determine what is appropriate behavior when they are faced with conflicting norms
      within a given situation. Participants tasted cookies while alone or while
      observed by the experimenter. Furthermore, participants were assigned to either a
      "no norm" condition in which they were given no indication of how much other
      people in the study had eaten, an "inhibition norm" condition in which they were
      led to believe that others had eaten minimally, or an "augmentation norm"
      condition in which they were led to believe that others in the study had eaten a
      lot. When they were alone, participants were influenced by the norms; but when
      they were observed, they ate minimally, regardless of the norms to which they
      were exposed. It seems that a norm for minimal eating superseded a matching norm
      which prescribes that people should use the intake of their peers as a guide for
      appropriate behavior. Implications of these findings and limitations of the study
      were discussed.

PMID- 11237353
TI  - Consumer involvement in seafood as family meals in Norway: an application of the
      expectancy-value approach.
AB  - A theoretical model of involvement in consumption of food products was tested in
      a representative survey of Norwegian households for the particular case of
      consuming seafood as a common family meal. The empirical study is based on using
      structural equation approach to test construct validity of measures and the
      empirical fit of the theoretical model. Attitudes, negative feelings, social
      norms and moral obligation were proved to be important, reliable and different
      constructs and explained 63% of the variation in seafood involvement. Negative
      feelings and moral obligation was the most important antecedents of involvement.
      Both our proposed model and modified model with seafood involvement as a mediator
      fit well with the data and proved our expectations in a promising way.

PMID- 11237354
TI  - Stress-induced eating: an alternative method for inducing ego-threatening stress.
AB  - This study was designed to assess the effectiveness of a modified Stroop test as
      a method of inducing ego-threatening stress in dieters. Twenty females completed
      a Stroop task and watched a fearful film, and then consumed ice cream, ad
      libitum, under the guise of a tasting-test. It was predicted that the Stroop task
      would trigger greater consumption of ice cream than a fearful film, and that this
      effect would be more pronounced for binge-eaters than non-binge-eaters. More ice
      cream was consumed following the Stroop task, however both binge-eaters and non
      binge-eaters consumed more ice cream after the Stroop task than the film-task.
      This data suggests that the ego-threatening Stroop test has potential as a
      standardized method for use in studies of stress-induced eating.

PMID- 11237356
TI  - Survival of Brucella abortus strain RB51 lyophilized and as liquid vaccine under
      different storage conditions.
AB  - Brucella abortus strain RB51 (SRB51) is a new cattle vaccine that is approved for
      use in the U.S. for prevention of brucellosis. At the present time, other
      countries are implementing or considering the use of SRB51 vaccine in their
      brucellosis control programs. In the current study, the effect of three
      stabilizing media, two fill volumes (1 and 3 ml), and three storage temperatures
      (-25, 4 and 25 degrees C) on the viability of lyophilized SRB51 over a 52 week
      period was determined. The effects of three concentrations of bacteria (5 x
      10(8), 1 x 10(9), or 5 x 10(9) cfu/ml) and two storage temperatures (4 or 25
      degrees C) on viability of liquid SRB51 vaccine were also determined. For
      lyophilized strain RB51 vaccine, fill volume did not influence viability (P>
      0.05) during lyophilization. Although fill volume did not influence viability
      during storage in World Health Organization (WHO) media or media containing both
      WHO and Lactose Salt (LS) media, 1 ml fill volumes of SRB51 in LS media had
      greater (P< 0.05) viability when compared to 3 ml fill volumes. Lyophilized SRB51
      vaccine stored at 25 degrees C had a more rapid decline in viability (P< 0.05)
      when compared to vaccine stored at -25 or 4 degrees C. With the exception of the
      3-ml fill volumes of LS media, all three stabilizing media were similar in
      maintaining viability of SRB51 at -25 degrees C storage temperatures. However,
      when compared to WHO or WHO/LS media, stabilization in LS media was associated
      with a more rapid decline in viability during storage at 4 or 25 degrees C (P<
      0.05). Initial SRB51 concentration in liquid vaccine did not influence (P> 0.05)
      viability during storage at 4 or 25 degrees C. When compared to liquid SRB51
      vaccine stored at 25 degrees C, storage at 4 degrees C was associated with a
      slower decline in viability (P< 0.05) during 12 weeks of storage. Biochemical and
      morphological characteristics of SRB51 were stable under the storage conditions
      utilized in the present study. This study suggests that viability of SRB51 can be
      readily maintained during storage as a lyophilized or liquid brucellosis vaccine.

PMID- 11237357
TI  - Key points for the development of mouse immunogenicity test as potency assay for
      acellular pertussis vaccines.
AB  - According to WHO and the European Pharmacopoeia, the current potency test for
      acellular pertussis vaccines is a mouse immunogenicity assay assessing
      consistency of production from batch to batch. The assay compares the batch under
      control with a reference vaccine of documented clinical efficacy. This study
      describes and illustrates critical aspects of the assay, based on our experience
      on a tricomponent vaccine: validation of immunoassay to quantify mouse antibody
      response, choice of vaccine immunising doses in the three-doses model, treatment
      of non-responder mice for calculations, establishment of assay validity criteria.

PMID- 11237358
TI  - The determination of phosphorus in Haemophilus influenzae type b conjugate
      vaccines by inductively coupled plasma-atomic emission spectrometry.
AB  - This study describes a method for the determination of phosphorus in lyophilized
      Haemophilus influenzae type b conjugate vaccines by inductively coupled plasma
      atomic emission spectroscopy (ICP-AES). The concentration of polysaccharide is
      directly related to the concentration of phosphorus as measured in the
      laboratory. Phosphorus is present in the polyribosyl-ribitol phosphate (PRP)
      group of the Haemophilus influenzae type b conjugate vaccine. The repeating unit
      of PRP is 3-B-D ribose[1-1]ribitol-5-phosphate. Phosphorus in the final container
      is measured in microg per dose. The amount of PRP is calculated from this and
      reported in microg per dose. The Haemophilus influenzae type b conjugate vaccine
      was analyzed for phosphorus content within the range of 1.34 to 2.02 microg
      phosphorus per ml. The relative difference of phosphorus concentrations
      determined by the ICP-AES method from the phosphorus concentrations determined by
      the traditional colorimetric molybdate method ranged from 2.2 to 10.6%.
      Phosphorus spike recovery for the vaccine ranged from 93 to 99% (1.93+/-0.13
      microg P/ml). The phosphorus determination of NIST SRM 3139 phosphorus
      spectrometric solution differed by 3.0% from the certified phosphorus value
      (10.00 mg P/ml).

PMID- 11237359
TI  - Hepatitis A immunoglobulin: an international collaborative study to establish the
      second international standard.
AB  - A collaborative study was carried out to assess the suitability of a candidate
      replacement material for the International Standard for hepatitis A
      immunoglobulin, which was found to be reactive for HCV RNA, and to calibrate it
      in International Units. The candidate standard, coded 97/646, was derived from a
      bulk of 16% immunoglobulin supplied by the Central Laboratory of the Netherlands
      Red Cross, Amsterdam, and diluted 1 in 2 in H2O resulting in a final
      immunoglobulin concentration of 8%. Sixteen laboratories from 11 countries
      participated in the study and contributed data from 64 assays performed using six
      commercial assay kits and four in-house methods. All assays were analysed as
      parallel line bioassays comparing assay response with log concentration. The
      overall mean potency of the candidate replacement immunoglobulin standard,
      97/646, relative to the International Standard for hepatitis A immunoglobulin,
      was 98.6 IU/ml. A freeze-dried serum preparation, 97/648, was also calibrated in
      this study and had a potency of 22.64 IU/ml. The Second International Standard
      for hepatitis A immunoglobulin, human, was established by the World Health
      Organisation Expert Committee on Biological Standardisation in 1998 with a
      potency of 49 IU per ampoule when reconstituted in 0.5 ml.

PMID- 11237360
TI  - Investigation of an aerosol challenge model as alternative to the intracerebral
      mouse protection test for potency assay of whole cell pertussis vaccines.
AB  - The current potency test for whole cell pertussis vaccines, the intracerebral
      mouse protection test, is still the only assay which has shown a correlation with
      protection in children. However, it has considerable disadvantages as it uses a
      severe challenge procedure and the results tend to show significant intra- and
      inter-laboratory variation. An alternative assay based on non-lethal aerosol
      challenge of mice has been investigated as a replacement for the current
      intracerebral mouse protection test. Evaluation of this indicated that the
      aerosol system allowed consistent inoculation of bacteria into mice and gave good
      reproducibility. The protective capacity of different vaccine preparations was
      distinguished by this assay. Furthermore, the viable counts of Bordetella
      pertussis in the lungs of challenged mice were immunisation dose-dependent, which
      allowed the relative potency of vaccines to be calculated. Comparison of potency
      of five batches of vaccine from different manufacturers assayed by both the
      intracerebral and the aerosol challenge methods ranked the vaccines in identical
      order. The results suggest that this method has potential for use as a potency
      test for whole cell pertussis vaccine which would result in a great reduction in
      the number of animals used. It would also replace the lethal challenge by a non
      lethal procedure and thereby avoid the use of the severe intracerebral challenge
      procedure.

PMID- 11237363
TI  - Probing spatial working memory with the Corsi Blocks task.
AB  - The Corsi Blocks task (CBT) measures spatial memory span, but methodological
      differences across previous studies prevent a clear appreciation of perceptual,
      memory, and motor contributions to spatial span. CBT performance in a standard
      condition was compared to performance with longer encoding intervals (3 vs 1 s),
      longer memory intervals (9 vs 1 s), or fewer response alternatives (all nine vs
      only the relevant positions). All experiments also contrasted ascending vs
      descending order of item difficulty and recorded response-initiation times.
      Performance improved with longer encoding and maintenance intervals and with
      fewer response alternatives. Item order had no reliable effects. Response
      initiation times were a useful additional measure of spatial span. Implications
      of these findings for research using the CBT are discussed.

PMID- 11237361
TI  - In vitro potency assay for hepatitis A vaccines: development of a unique
      economical test.
AB  - Prior to the official release of each Hepatitis A vaccine lot to the market, a
      quality control performed by a National Control Authority requires an in vivo or
      an in vitro potency assay. At the beginning of our work, no standardised in vitro
      test common to all hepatitis A vaccines was available for both manufacturers and
      National Control Laboratories. In this study, a unique polyvalent enzyme-linked
      immunosorbent assay (ELISA) method was developed to appraise all commercially
      available HAV vaccines. After comparing a direct and an indirect sandwich method
      with commercial antibodies, the indirect assay was selected and an evaluation of
      sensitivity, linearity, accuracy and precision was performed before being applied
      to HAV antigen determination from four different manufacturers. The results are
      satisfactory and incline us to use routinely this method to release Hepatitis A
      vaccines.

PMID- 11237364
TI  - Categorical and coordinate spatial processing: more on contributions of the
      transient/magnocellular visual system.
AB  - Observers were presented with stimuli consisting of a line and two horizontally
      separated dots. A categorical spatial task required observers to indicate whether
      the dots were above or below the line and a coordinate spatial task required
      observers to indicate whether the line could fit into the space between the two
      dots. Coordinate (but not categorical) spatial processing was less accurate and
      took longer with stimuli presented on a red background than with stimuli
      presented on a green background, even though the background color varied randomly
      from trial to trial and the viewing screen remained gray between trials. Because
      the color red attenuates processing in the transient/magnocellular visual system,
      these results suggest that coordinate spatial processing is dependent on that
      pathway. Furthermore, such effects do not involve mechanisms of perceptual
      adaptation that depend on the same color background being present throughout an
      experiment or for a prolonged period of time. As in earlier experiments, the
      effects of color condition were the same regardless of which visual field (and
      hemisphere) received the stimulus information. However, in contrast to the
      results of earlier experiments, there was no significant interaction of task and
      visual field.

PMID- 11237365
TI  - A developmental phonological short-term memory deficit: a case study.
AB  - A developmental case of phonological short-term memory deficit was studied in a
      highly educated subject. The subject, BS, who had obtained a Ph.D. in molecular
      biology, demonstrated striking deficits on some short-term memory tasks,
      particularly for auditorily presented nonword lists. With visual presentation and
      with meaningful words, he often scored at a normal level. The results indicate a
      deficit in retaining phonological information but an ability to use visual,
      lexical, and semantic information to boost recall. Despite this phonological
      short-term memory deficit, BS scored at a normal level on a syntactic
      comprehension test and on reading of nonwords. He was impaired, however, on
      repeated list learning, learning of foreign vocabulary, and transcribing dictated
      materials. The implications of these results for models of short-term memory and
      the uses of phonological retention in cognitive processing are discussed.

PMID- 11237366
TI  - Distinct contribution of the striatum and cerebellum to motor learning.
AB  - The striatum and cerebellum have been shown to be key structures of a distributed
      system for the control of skilled movements. However, the mechanisms under which
      they operate remain unclear. This study compared the performance of patients with
      Parkinson's disease (PD) or with cerebellar damage (CE) to that of age-matched
      controls. Each group performed two visuomotor paradigms: a random variant of the
      serial reaction time (SRT) task that tested the subject's ability to make
      efficient stimulus-response associations and an adapted version of the mirror
      tracing task that measured their capacity to combine simple movements into
      complex ones. PD patients with bilateral striatal damage showed an impaired
      learning profile on the SRT task and a normal facilitation effect in the tracing
      task, while CE patients showed the reverse pattern. Although further research is
      needed, the present findings suggest that the striatum and cerebellum are
      involved in distinct learning mechanisms.

PMID- 11237367
TI  - A biologically plausible model of associative memory which uses disinhibition
      rather than long-term potentiation.
AB  - Mammalian memory is commonly "explained" in terms of long-term potentiation (LTP)
      of excitatory synapses. However, depotentiation of inhibitory pathways
      (disinhibition) is also a known phenomenon in the brain. Artificial neural
      networks which are offered as partial models of the cerebrum traditionally encode
      memory by the potentiation of excitatory "synapses" in a manner which is thought
      of as analogous to LTP. Analysis shows that such models have seriously limited
      storage capacities. The models also depend on mechanisms which do not appear to
      be biologically plausible. This paper demonstrates that these difficulties are
      avoided by encoding memory by means of disinhibition rather than LTP. The
      resulting models are simple and plausible, though unconventional.

PMID- 11237368
TI  - Large individual differences in minor ear output during dichotic listening.
AB  - Using dichotic consonant-vowel (CV) stimuli, 150 highly educated adults were
      segregated into two groups. In the high-output group (n = 63), the mean number of
      CV syllables reported by the minor ear was more than half that of the major ear,
      while for the low-output group (n = 87), it was less than one-fourth. The low
      minor ear performance of the latter group immediately disappeared when CV
      syllables were separated by 90 ms. These subjects (44 male, 43 females) were
      unaware of their temporary minor ear incapacities. Although the mechanism and
      brain laterality significance of this phenomenon remain to be clarified,
      preliminary research indicates that members of each of these two groups have
      other differences in common.

PMID- 11237369
TI  - Significance of paradoxical leftward error of line bisection in left unilateral
      spatial neglect.
AB  - We intended to determine if leftward error of line bisection means "right" or
      "left" neglect in a patient with left unilateral spatial neglect. The patient
      placed the subjective midpoint to the left of the true center when bisecting
      lines without cueing. By contrast, when cued to the left endpoint, he showed
      typical rightward errors that became greater as longer lines were presented.
      Cueing to the right endpoint increased leftward errors compared with the
      bisections without cueing. The results suggest that paradoxical leftward error of
      line bisection is a form of "left" unilateral spatial neglect in that the
      shortness of the left extent is ignored.

PMID- 11237370
TI  - Animals and artifacts may not be treated equally: differentiating strong and weak
      forms of category-specific visual agnosia.
AB  - We examined a categorical dissociation hypothesis of category-specific agnosia
      using hierarchical regression to predict the naming responses of three agnosia
      patients while controlling a wide variety of perceptual and conceptual between
      category differences. The living-nonliving distinction remained a significant
      predictor for two of the patients after controlling for all the other factors.
      For one remaining patient, the categorical variable was not significant once the
      form-function correlation of different objects was controlled. We argue that the
      visual system may use various subprocesses at different stages, some of which
      reflect true categorical organization and some of which reflect a unitary feature
      based system that distinguishes kinds.

PMID- 11237371
TI  - A rule-based categorization deficit in Alzheimer's disease?
AB  - This study examined the categorization processes that Alzheimer's disease (AD)
      patients use during assessments of semantic memory. Rule-based categorization
      involves the careful, analytic processing of strict criteria to determine
      category membership, particularly for items from graded categories with ambiguous
      category membership; similarity-based categorization requires an overall
      comparison of a test stimulus with a prototype or remembered exemplar of the
      category and is relatively effective for the rapid categorization of items with
      unambiguous category membership. To assess these processes in AD, patients were
      asked to decide the category membership of test stimuli for categories with
      poorly defined or fuzzy boundaries (e.g., VEGETABLE) and for categories with well
      defined boundaries (e.g., FEMALE) and then to judge the representativeness of the
      test stimulus for its chosen category. A subgroup of AD patients demonstrated a
      typical pattern of impaired semantic memory compared to healthy control subjects;
      that is, difficulty deciding the category membership of test items from fuzzy
      categories. Among these patients, we found no deficit in category membership
      decisions about items taken from well-defined categories. We also found that AD
      patients and healthy controls do not differ in their representativeness judgments
      of items within a correctly judged category. These findings are most consistent
      with the hypothesis that rule-based categorization difficulty limits semantic
      memory in AD.

PMID- 11237372
TI  - Impaired perception of vocal emotions in Parkinson's disease: influence of speech
      time processing and executive functioning.
AB  - Little is known about the underlying dimensions of impaired recognition of
      emotional prosody that is frequently observed in patients with Parkinson's
      disease (PD). Because patients with PD also suffer from working memory deficits
      and impaired time perception, the present study examined the contribution of (a)
      working memory (frontal executive functioning) and (b) processing of the acoustic
      parameter speech rate to the perception of emotional prosody in PD. Two acoustic
      parameters known to be important for emotional classifications (speech duration
      and pitch variability) were systematically varied in prosodic utterances. Twenty
      patients with PD and 16 healthy controls (matched for age, sex, and IQ)
      participated in the study. The findings imply that (1) working memory
      dysfunctions and perception of emotional prosody are not independent in PD, (2)
      PD and healthy control subjects perceived vocal emotions categorically along two
      acoustic manipulation continua, and (3) patients with PD show impairments in
      processing of speech rate information.

PMID- 11237374
TI  - Serum vascular endothelial growth factor load and interleukin-6 in cancer
      patients - reply.

PMID- 11237375
TI  - Menstrual and reproductive factors in relation to ovarian cancer risk.
AB  - We assessed menstrual and reproductive factors in relation to ovarian cancer risk
      in a large, population-based, case-control study. 563 cases in Massachusetts and
      New Hampshire were ascertained from hospitals and statewide tumour registries;
      control women (n = 523) were selected through random digit dialing and matched to
      case women by age and telephone sampling unit. We used multivariate logistic
      regression to evaluate factors in relation to risk of ovarian cancer and the
      major tumour histologic subtypes. Ovarian cancer risk was reduced among parous
      women, relative to nulliparous women (OR = 0.4; 95% CI = 0.3-0.6). Among parous
      women, higher parity (P = 0.0006), increased age at first (P = 0.03) or last (P =
      0.05) birth, and time since last birth (P = 0.04) were associated with reduced
      risk. Early pregnancy losses, abortions, and stillbirths were unrelated to risk,
      but preterm, term, and twin births were protective. Risk was lower among women
      who had breast-fed, relative to those who had not (OR = 0.7; 95% CI = 0.5-1.0),
      but the average duration of breast-feeding per child was unrelated to risk (P for
      trend = 0.21). Age at menarche and age at menopause were unrelated to risk
      overall, although increasing menarcheal age was protective among premenopausal
      women (P = 0.02). Menstrual cycle characteristics and symptoms were generally
      unrelated to risk, although cycle-related insomnia was associated with decreased
      risk (OR = 0.5; 95% CI = 0.3-0.8). We found no association between the type of
      sanitary product used during menstruation and ovarian cancer risk. In analyses by
      histologic subtype, reproductive and menstrual factors had most effect on risk of
      endometrioid/clear cell tumours, and least influential with regard to risk of
      mucinous tumours. Overall, our findings offer some support to current hypotheses
      of ovarian pathogenesis, and show aetiologic differences among the tumour
      subtypes.

PMID- 11237376
TI  - Morphine and alternative opioids in cancer pain: the EAPC recommendations.
AB  - An expert working group of the European Association for Palliative Care has
      revised and updated its guidelines on the use of morphine in the management of
      cancer pain. The revised recommendations presented here give guidance on the use
      of morphine and the alternative strong opioid analgesics which have been
      introduced in many parts of the world in recent years. Practical strategies for
      dealing with difficult situations are described presenting a consensus view where
      supporting evidence is lacking. The strength of the evidence on which each
      recommendation is based is indicated.

PMID- 11237377
TI  - Cancer risk perceptions and distress among women attending a familial ovarian
      cancer clinic.
AB  - Of 230 women referred to a familial ovarian cancer clinic, 196 (85%) completed a
      questionnaire before they attended. The data collected included pre-counselling
      risk perceptions and an assessment of distress. Respondents were more likely to
      underestimate (44%) than overestimate (19%) their risk. Those with a family
      history of breast and ovarian cancer (HBOC) were particularly likely to
      underestimate their ovarian cancer risk. The variables assessed in this study -
      sociodemographic, family history, distress, anxiety proneness, coping style and
      beliefs about health control - explained little of the observed variation in
      accuracy of risk perception. On the General Health Questionnaire (GHQ-30) 30% of
      the sample obtained scores above the cut-off (>/= 6) recommended for screening
      for 'case-level' psychological distress. Women exhibiting case-level distress
      were more likely to overestimate their risk (OR = 2.3). On univariate analysis
      low internal locus of control was associated with 'case-level' distress (P =
      0.008). On multiple regression the best predictors of 'caseness' were high-trait
      anxiety, being a graduate and inaccurate risk perception. There was no difference
      in the level of distress shown by women with HBOC vs. those with a history of
      ovarian cancer only. Implications of these findings for the counselling needs of
      the women are discussed. The effectiveness of the clinic in improving the
      accuracy of risk perceptions and relieving distress is being assessed.

PMID- 11237378
TI  - 5-fluorouracil steady state pharmacokinetics and outcome in patients receiving
      protracted venous infusion for advanced colorectal cancer.
AB  - PVI 5FU gives increased response rates and reduced toxicity when compared to
      bolus 5FU (J Clin Oncol 1989, 425-432). PVI 5FU administration was reported to
      give highly variable (>1000-fold) plasma 5FU concentrations at steady state (FU
      Css) which correlated with toxicity (Ann Oncol 1996, 47-53); but only 19 patients
      were studied. Therefore, we performed a study of PVI 5FU in 61 patients with
      advanced colorectal cancer to assess the variability (inter- and intra-subject)
      in 5FU Css associated with PVI 5FU (300 mg m(-2)day(-1)) and to attempt to
      correlate pharmacodynamic end-points (anti-tumour activity, toxicity) with 5FU
      Css as a prelude to 'exposure-guided' 5FU administration. All 5FU sampling was
      performed between 10 am and noon. PVI 5FU administration continued to 26 weeks in
      patients with disease improvement or stabilization. The response rate was 26%
      (33% stable disease) and median survival was 11 months. Hand-foot syndrome was
      the most common dose limiting toxicity. Variability in 5FU(300)Css was
      considerably less than previously reported; 94 +/- 25 ng ml(-1)(CV = 27%). No
      relationships were demonstrated between subject mean 5FU(300)Css and PD end
      points such as response, mucositis, diarrhoea and hand-foot syndrome. The lack of
      correlation suggests that measurement of 5FU concentrations should not be used to
      individualize dosing in patients receiving PVI 5FU for advanced colorectal
      cancer.

PMID- 11237381
TI  - Telomerase activity in plasma cell dyscrasias.
AB  - Activation of telomerase is essential for in vitro cellular immortalization and
      tumorigenesis. In the present study, we investigated telomerase activation and
      its implications in plasma cell dyscrasias including monoclonal gammopathy of
      undetermined significance (MGUS), multiple myeloma (MM) and plasma cell leukaemia
      (PCL). All 5 patients with MGUS exhibited normal levels of telomerase activity in
      their plasma cells. Elevated telomerase activity was found in the samples from
      21/27 patients with MM and 4/4 with PCL. In addition, 4 myeloma cell lines all
      expressed high levels of telomerase activity. The expression of telomerase
      reverse transcriptase (hTERT) and telomerase RNA template (hTER) was positively
      associated with the levels of telomerase activity in MM/PCL. Tankyrase expression
      was upregulated, concomitant with the induction of hTERT and activation of
      telomerase in MM/PCL. The present findings indicate that MGUS cells may not be
      immortalized and that activation of telomerase plays a role in the malignant
      transformation from MGUS to MM.

PMID- 11237379
TI  - Phase I trial and pharmacological study of a 3-hour paclitaxel infusion in
      children with refractory solid tumours: a SFOP study.
AB  - The maximum tolerated dose of paclitaxel administered by 24-hour continuous
      infusion in children is known. Short infusion might offer equivalent antitumour
      efficacy and reduced haematological toxicity, without increasing the allergic
      risk. Our aims were to determine the maximum tolerated dose and the
      pharmacokinetics of paclitaxel in children when administered in 3-h infusion
      every 3 weeks. Patients older than 6 months, younger than 20 years with
      refractory malignant solid tumours were eligible when they satisfied standard
      haematological, renal, hepatic and cardiologic inclusion criteria with life
      expectancy exceeding 8 weeks. Paclitaxel was administered as a 3-hour infusion
      after premedication (dexamethasone, dexchlorpheniramine). Pharmacokinetic
      analysis and solvent assays (ethanol, cremophor) were performed during the first
      course. 20 courses were studied in 17 patients; 4 dosage levels were investigated
      (240 to 420 mg/m(2)). No dose-limiting haematological toxicity was observed.
      Severe acute neurological and allergic toxicity was encountered. One treatment
      related death occurred just after the infusion at the highest dosage. Delayed
      peripheral neurotoxicity and moderate allergic reactions were also encountered.
      Pharmacokinetic analysis showed dose-dependent clearance of paclitaxel and
      elevated blood ethanol and Cremophor EL levels. Although no limiting
      haematological toxicity was reached, we do not recommend this paclitaxel schedule
      in children because of its acute neurological toxicity.

PMID- 11237380
TI  - Alpha-interferon does not increase the efficacy of 5-fluorouracil in advanced
      colorectal cancer.
AB  - Two meta-analyses were conducted to quantify the benefit of combining alpha-IFN
      to 5FU in advanced colorectal cancer in terms of tumour response and survival.
      Analyses were based on a total of 3254 individual patient data provided by
      principal investigators of each trial. The meta-analysis of 5FU +/- LV vs. 5FU +/
      LV + alpha-IFN combined 12 trials and 1766 patients. The meta-analysis failed to
      show any statistically significant difference between the two treatment groups in
      terms of tumour response or survival. Overall tumour response rates were 25% for
      patients receiving no alpha-IFN vs. 24% for patients receiving alpha-IFN
      (relative risk, RR = 1.02), and median survivals were 11.4 months for patients
      receiving no alpha-IFN vs. 11.5 months for patients receiving alpha-IFN (hazard
      ratio, HR = 0.95). The meta-analysis of 5FU + LV vs. 5FU + alpha-IFN combined 7
      trials, and 1488 patients. This meta-analysis showed an advantage for 5FU + LV
      over 5FU + alpha-IFN which was statistically significant in terms of tumour
      response (23% vs. 18%; RR = 1.26;P = 0.042), and of a borderline significance for
      overall survival (HR = 1.11;P = 0.066). Metastases confined to the liver and
      primary rectal tumours were independent favourable prognostic factors for tumour
      response, whereas good performance status, metastases confined to the liver or
      confined to the lung, and primary tumour in the rectum were independent
      favourable prognostic factors for survival. We conclude that alpha-IFN does not
      increase the efficacy of 5FU or of 5FU + LV, and that 5FU + alpha-IFN is
      significantly inferior to 5FU + LV, for patients with advanced colorectal cancer.

PMID- 11237382
TI  - Proportion of infiltrating IgG-binding immune cells predict for tumour hypoxia.
AB  - Macrophages can account for up to 50% of tumour mass and secrete many angiogenic
      factors. Furthermore, tumour hypoxia is thought to play a major role in the
      activation of macrophages and the regulation of angiogenesis. In this paper, we
      demonstrate a strong correlation between hypoxia and the recruitment of immune
      cells binding to IgG in 8 experimental tumours. We provide evidence that IgG
      binding immune cells in 3 tumour lines are predominately composed of macrophages.
      Reduced oxygenation may act as a stimulus for recruitment of immune cells to the
      tumour mass, and the detection of either IgG-positive host cells or macrophages
      may offer an alternative method for monitoring tumour hypoxia.

PMID- 11237383
TI  - Detection of circulating carcinoma cells by telomerase activity.
AB  - Telomerase has been shown to be a marker of epithelial cancer cells. We developed
      a method that allows the detection of circulating carcinoma cells in the blood of
      cancer patients. Circulating epithelial cells are harvested from peripheral blood
      mononuclear cells by immunomagnetic separation using BerEP4-coated beads. A
      telomeric repeat amplification protocol (TRAP)-ELISA is then used to measure
      telomerase in harvested epithelial cells. This method is specific and sensitive
      as demonstrated by experiments using BerEP4-positive and negative cell lines.
      Whereas we never found telomerase activity in harvested epithelial cells (HEC)
      samples from 30/30 healthy donors, we have detected telomerase activity in HEC
      from 11/15 (73%) patients with stage IIIB or IV non-small cell lung cancer
      (NSCLC) patients and from 8/11 (72%) stage C or D (Dukes classification) colon
      cancer patients. This non-invasive method could be of great value as a diagnostic
      or prognostic marker, or for monitoring cancer progression.

PMID- 11237385
TI  - Human kallikrein gene 5 (KLK5) expression is an indicator of poor prognosis in
      ovarian cancer.
AB  - Kallikrein gene 5 (KLK5, also known as KLK-L2), located on chromosome 19q13.4, is
      one of the newly identified members of the kallikrein gene family, which is a
      subgroup of the serine protease enzyme family. In normal human tissues, KLK5 is
      highly expressed in skin, mammary gland and testis. Preliminary RT-PCR analysis
      has indicated that KLK5 is expressed in a subset of ovarian tumours. We have thus
      hypothesized that KLK5 may be a new prognostic indicator in ovarian cancer. We
      have examined the mRNA expression of KLK5 in 142 malignant ovarian tissues.
      Tumours were pulverized, total RNA was extracted, and cDNA was prepared by
      reverse transcription. KLK5 was amplified by PCR using gene specific primers, and
      the identity of the PCR product was verified by sequencing. Ovarian tissues were
      then classified as KLK5 positive or negative, based on ethidium bromide staining
      of the PCR product on agarose gels. KLK5 was found to be highly expressed in
      58/142 (41%) of ovarian cancer samples while its level of expression was very low
      in normal ovarian tissues. We found a strong positive relation between KLK5
      expression and tumour grade (P = 0.006) and disease stage (P = 0.027). Univariate
      survival analysis revealed that patients with ovarian tumours positive for KLK5
      expression had an increased risk for relapse and death (P = 0.018 and 0.022,
      respectively). In multivariate analysis, KLK5 expression showed independent
      prognostic value only in the subset of tumours with lower grade disease (grades I
      and II). We conclude that KLK5 expression is associated with more aggressive
      forms of epithelial ovarian carcinoma and has indepdent prognostic value in low
      grade tumours.

PMID- 11237384
TI  - A new human chromogranin 'A' immunoradiometric assay for the diagnosis of
      neuroendocrine tumours.
AB  - We investigated whether plasma chromogranin A (CgA), measured by a new
      immunoradiometric assay, may be a sensitive and specific marker of
      phaeochromocytoma and of other neuroendocrine tumours. This study involved 121
      patients of whom 20 with phaeochromocytoma, 28 with other neuroendocrine tumours
      (19 gastroenteropancreatic tumors, 3 medullary thyroid and 6 small cell lung
      carcinomas), 25 with solid nonfunctioning adrenocortical tumours and 48 with
      essential hypertension. In addition, 130 normal subjects were taken as controls.
      Plasma catecholamines were measured by using high-performance liquid
      chromatography, and CgA by a two-site sandwich immunoradiometric assay involving
      monoclonal antibodies raised against the unprocessed central domain (145-245) of
      human CgA. Plasma CgA in controls (49.0 +/- 3.1 ng ml(-1), mean +/- SE) and in
      essential hypertensives (50.8 +/- 3.5 ng ml(-1)) was lower (P< 0.0001) than in
      adrenocortical tumours (91.8 +/- 13.2 ng ml(-1)), in phaeochromocytomas (254 +/-
      49 ng ml(-1)) and in patients with other neuroendocrine tumours (469 +/- 84 ng
      ml(-1)). Plasma CgA and catecholamines identified 13 and 18 out of 20
      phaeochromocytomas with sensitivity of 65% and 90%, respectively. Combined
      measurement of both markers improved sensitivity up to 100%. In the other
      neuroendocrine tumours, CgA was abnormal in 23/28 cases (sensitivity 82%) and in
      6 it was the only circulating marker of disease. In gastroenteropancreatic
      tumours, CgA measurement identified all cases (sensitivity 100%). Specificity of
      CgA in patients with essential hypertension was 98%. In conclusion, CgA
      determination showed high sensitivity in identifying gastroenteropancreatic
      tumours and, in association with catecholamines, in detecting patients with
      phaeochromocytoma. CgA sometimes appeared to be the only circulating marker of
      disease. Since the specificity of CgA proved to be excellent, this assay may be
      useful for diagnosis both of functioning and non-functioning neuroendocrine
      tumours.

PMID- 11237386
TI  - Expression of apoptosis-related markers and clinical outcome in patients with
      advanced colorectal cancer.
AB  - The clinical relevance of bax and bcl-2 protein expression has been investigated
      in 84 patients with recurrent or metastatic colorectal cancer submitted to a
      chemotherapy regimen including methotrexate and fluorouracil/leucovorin.
      Cytoplasmic immunostaining of bax and bcl-2 was present in 65.5% and 38%,
      respectively, of the tumours. No association was found between bax and bcl-2 or
      between p53 and bax or bcl-2 protein expression. Moreover, the biomarkers were
      unrelated to patient and tumour characteristics known to affect the clinical
      outcome of colorectal cancer patients. In general, the apoptosis-related markers
      did not appear indicative of short- and long-term clinical response nor of
      prognosis. Bcl-2-negative lesions were more frequent among patients who reached
      an objective clinical response, which is in agreement with previously reported
      data regarding other tumour types. When the interrelationship between p53 and bax
      expression was examined, a better response rate (40%) was found for patients
      whose tumours did not express p53 and bax, and a better prognosis (2-year
      probability of overall survival 75%) for patients with p53-positive and bax
      negative tumours. In the present series of patients with advanced colorectal
      cancer submitted to systemic chemotherapy we did not find a clear association
      between expression of apoptosis-related markers and clinical outcome, even in the
      subset of patients in which the apoptotic index as determined by the TUNEL
      approach was investigated.

PMID- 11237387
TI  - Differential patterns of stromelysin-2 (MMP-10) and MT1-MMP (MMP-14) expression
      in epithelial skin cancers.
AB  - Co-expression of several members of the matrix metalloproteinase (MMP) family is
      characteristic of human malignant tumours. To investigate the role of stromelysin
      2 (MMP-10) in growth and invasion of skin tumours, we studied cutaneous
      carcinomas with high metastatic capacity (squamous cell carcinomas, SCCs), only
      locally destructive tumours (basal cell carcinomas, BCCs) and pre-malignant
      lesions (Bowen's disease and actinic keratosis) using in situ hybridization.
      Expression of MMP-10 was compared with that of stromelysin-1 (MMP-3) and of MT1
      MMP, the expression of which has been shown to correlate with tumour
      invasiveness. MMP-10 was expressed in 13/21 SSCs and 11/19 BCCs only in
      epithelial laminin-5 positive cancer cells, while premalignant lesions were
      entirely negative. MT1-MMP mRNA was detected in 19/21 SCCs both in epithelial
      cancer cells and stromal fibroblasts and in 14/18 BCCs only in fibroblasts. The
      level of MMP-10 was upregulated in a cutaneous SCC cell line (UT-SCC-7) by
      transforming growth factor-alpha and keratinocyte growth factor, and by
      interferon-gamma in combination with transforming growth factor-beta1 and tumour
      necrosis factor-alpha both in UT-SCC-7 and HaCaT cells. Our results show that MMP
      10 expression does not correlate with the invasive behaviour of tumours as
      assessed by their histology and MT1-MMP expression, but may be induced by the
      wound healing and inflammatory matrix remodelling events associated with skin
      tumours.

PMID- 11237388
TI  - Signal transduction activated by the cancer chemopreventive isothiocyanates:
      cleavage of BID protein, tyrosine phosphorylation and activation of JNK.
AB  - Phenethyl isothiocyanate and allyl isothiocyanate induce apoptosis of human
      leukaemia HL60 cells in vitro. Apoptosis was associated with cleavage of p22 BID
      protein to p15, p13 and p11 fragments and activation of JNK and tyrosine
      phosphorylation (18 kDa and 45 kDa proteins). All these effects and apoptosis
      were prevented by exogenous glutathione (15 mM). Protein tyrosine phosphatase
      activity was unchanged. The general caspase inhibitor Z-VAD-fmk prevented
      apoptosis but not JNK activation - excluding a role for caspases in JNK
      activation, whereas curcumin prevented JNK activation but only delayed apoptosis.
      This suggests that in isothiocyanate-induced apoptosis, the caspase pathway has
      an essential role, the JNK pathway a supporting role, and inhibition of protein
      tyrosine phosphatases is not involved.

PMID- 11237389
TI  - Direct evidence for a bystander effect of ionizing radiation in primary human
      fibroblasts.
AB  - Bystander responses underlie some of the current efforts to develop gene therapy
      approaches for cancer treatment. Similarly, they may have a role in strategies to
      treat tumours with targeted radioisotopes. In this study we show direct evidence
      for the production of a radiation-induced bystander response in primary human
      fibroblasts. We utilize a novel approach of using a charged-particle microbeam,
      which allows individual cells within a population to be selected and targeted
      with counted charged particles. Individual primary human fibroblasts within a
      population of 600-800 cells were targeted with between 1 and 15 helium ions
      (effectively, alpha-particles). The charged particles were delivered through the
      centre of the nucleus with an accuracy of +/- 2 micrometer and a detection and
      counting efficiency of greater than 99%. When scored 3 days later, even though
      only a single cell had been targeted, typically an additional 80-100 damaged
      cells were observed in the surviving population of about 5000 cells. The yield of
      damaged cells was independent of the number of charged particles delivered to the
      targeted cell. Similar results of a 2-3-fold increase in the background level of
      damage present in the population were observed whether 1 or 4 cells were targeted
      within the dish. Also, when 200 cells within one quadrant of the dish were
      exposed to radiation, there was a 2-3-fold increase in the damage level in an
      unexposed quadrant of the dish. This effect was independent of the presence of
      serum in the culture medium and was only observed when a cell was targeted, but
      not when only the medium was exposed, confirming that a cell-mediated response is
      involved.

PMID- 11237390
TI  - Circumvention of ara-C resistance by aphidicolin in blast cells from patients
      with AML.
AB  - Treatment failure in AML is often attributed to P-glycoprotein-associated
      multidrug resistance. However, the importance of increased DNA repair in
      resistant cells is becoming more apparent. In order to investigate the ability of
      the DNA repair inhibitor aphidicolin to modulate drug resistance, we continually
      exposed blasts cells, isolated from 22 patients with AML, to a variety of agents
      +/- 15 microM aphidicolin for 48 hours. Cell survival was measured using the MTT
      assay. Overall, there was no significant effect of aphidicolin on sensitivity to
      daunorubicin, doxorubicin, etoposide or fludarabine. However, there was a marked
      increase in sensitivity to ara-C with a median 4.75-fold increase overall (range
      0.8-80-fold;P< 0.005). The effect of aphidicolin was significantly greater in
      blast cells found resistant in vitro to ara-C (8.9-fold compared to 2.12-fold, P<
      0.01). This observation was further validated by the correlation between ara-C
      LC(50)and extent of modulation effect (P< 0.05). Cells isolated from 10 cord
      blood samples were also tested in order to establish the haematological toxicity
      of combining ara-C and aphidicolin. The therapeutic index (LC(50)normal
      cells/tumour cells) for ara-C + aphidicolin was higher than that for ara-C alone
      suggesting no increased myelotoxicity for the combination. Increased cytotoxicity
      without increased haematotoxicity makes the combination of ara-C plus aphidicolin
      ideal for inclusion in future clinical trials.

PMID- 11237391
TI  - Anti-oestrogen resistant human breast cancer cell lines are more sensitive
      towards treatment with the vitamin D analogue EB1089 than parent MCF-7 cells.
AB  - Most breast cancer patients treated with anti-oestrogens will eventually develop
      resistance towards treatment. Therefore it is important to find new therapeutic
      agents effective for treatment of patients relapsing on anti-oestrogen. The
      vitamin D analogue EB1089 (Seocalcitol(TM)) is a promising new agent for
      treatment of breast cancer patients with advanced disease, and in this study we
      show that two different anti-oestrogen-resistant human breast cancer cell lines
      are more sensitive towards treatment with EB1089, than the parent MCF-7 cell
      line. The two resistant cell lines both express a lower content of the anti
      apoptotic protein Bcl-2, and we suggest that this may explain the higher
      sensitivity towards EB1089. The importance of Bcl-2 for response to EB1089 is
      supported by our observation that oestradiol abrogates the effect of EB1089 in
      cell lines which increase Bcl-2 in response to oestradiol treatment. Overall
      these results indicate that treatment with Seocalcitol(TM)may prove effective
      when patients become refractory to anti-oestrogen therapy, and that Bcl-2 may be
      used as a predictive marker.

PMID- 11237392
TI  - Magnetic resonance detects changes in phosphocholine associated with Ras
      activation and inhibition in NIH 3T3 cells.
AB  - Ras is frequently mutated in cancer, and novel therapies are being developed to
      target Ras signalling. To identify non-invasive surrogate markers of Ras
      activation and inhibition, we used(31)P magnetic resonance spectroscopy (MRS) and
      investigated NIH 3T3 cells compared to a mutant ras transfected counterpart. The
      MR spectra indicated that phosphocholine (PC) levels increased significantly from
      3 +/- 2 fmol cell(-1)in NIH 3T3 cells to 13 +/- 4 fmol cell(-1)in the transfected
      cells. The PC/NTP ratio increased significantly from 0.3 +/- 0.1 to 0.7 +/- 0.3.
      This could not be explained by either a faster proliferation rate or by
      alterations in cell cycle distribution. Both cell lines were treated with
      simvastatin, 17-AAG and R115777, agents which inhibit Ras signalling. Cell
      proliferation was inhibited in both cell lines. The spectrum of NIH 3T3 cells was
      not affected by treatment. In contrast, in the ras transfected cells growth
      inhibition was associated with an average 35 +/- 5% drop in PC levels and a
      comparable drop in PC/NTP. Thus the MRS visible increase in phosphocholine is
      associated with Ras activation, and response to treatment is associated with
      partial reversal of phosphocholine increase in ras transfected cells. MRS might
      therefore be a useful tool in detecting Ras activation and its inhibition
      following targeted therapies.

PMID- 11237393
TI  - Childhood acute leukaemia and residential 16.7 Hz magnetic fields in Germany.
AB  - We observed a moderate but statistically non-significant association between
      magnetic fields (MF) and childhood leukaemia. This is the first such study to
      cover residential exposure to 16.7 Hz (railway frequency) MF though based on few
      exposed subjects. Our study does not exclude a small excess risk, but the
      attributable risk must be very low. It is reassuring that neglecting 16.7 Hz MF
      in childhood cancer studies appears to have little effect on findings.

PMID- 11237394
TI  - Excess mortality from breast cancer 20 years after diagnosis when life expectancy
      is normal.
AB  - In a population-based study, causes of death were traced of 418 deceased breast
      cancer patients diagnosed in 1960-1979 who survived at least 10 years after
      diagnosis. The pattern of causes of death in these patients was compared with the
      general female population using standardized mortality ratios (SMRs). Of 418
      patients surviving at least 10 years, 196 (47%) died from breast cancer and 50
      (12%) died from another cancer. The SMR for breast cancer was 15.8 (95% CI: 13.1
      18.8) 10-14 years after diagnosis; it was still 4.7 (95% CI: 2.6-7.8) after 20
      years. Overall mortality was higher than expected 10-14 years after diagnosis
      (SMR: 1.3; 95% CI: 1.1-1.5), but lower after more than 20 years (SMR: 0.6; 95%
      CI: 0.4-0.7). Despite a normal (or even improved) life expectancy for breast
      cancer patients 20 years after diagnosis the risk of dying from this disease
      remained elevated.

PMID- 11237395
TI  - A probability model for predicting BRCA1 and BRCA2 mutations in breast and breast
      ovarian cancer families.
AB  - Germline mutations in BRCA1 and BRCA2 genes predispose to hereditary breast and
      ovarian cancer. Our aim was to find associations between the clinical
      characteristics and positive mutation status in 148 breast cancer families in
      order to predict the probability of finding a BRCA mutation in a family. Several
      factors were associated with mutations in univariate analysis, whereas in
      multivariate analysis (logistic regression with backward selection) only the age
      of the youngest breast cancer patient and the number of ovarian cancer cases in a
      family were independent predictors of BRCA mutations. A logistic model was
      devised to estimate the probability for a family of harbouring a mutation in
      either BRCA1 or BRCA2. Altogether, 63 out of 148 families (43%) and 28 out of 29
      (97%) mutation carrier families obtained probabilities over 10%. The mean
      probability was 55% for mutation-positive families and 11% for mutation-negative
      families. The models by Couch et al (1997) and Shattuck-Eidens et al (1997)
      previously designed for BRCA1 were also tested for their applicability to
      distinguish carrier families with mutations in either gene. The probability model
      should be a useful tool in genetic counselling and focusing the mutation
      analyses, and thus increasing also the cost-effectiveness of the genetic
      screening.

PMID- 11237396
TI  - Betel quid chewing as a risk factor for hepatocellular carcinoma: a case-control
      study.
AB  - The role of betel quid chewing in the aetiology of hepatocellular carcinoma (HCC)
      was evaluated in a case-control study including 263 pairs of age- and sex-matched
      HCC patients and healthy controls. Serum hepatitis B surface antigen (HBsAg), and
      antibodies to hepatitis C virus (anti-HCV) were determined, and standardized
      personal interview conducted using a structured questionnaire. Multivariate
      analysis indicated that betel quid chewing (odds ratio (OR), 3.49; 95% confidence
      interval (CI), 1.74-6.96), HBsAg (OR, 16.69; 95% CI, 9.92-28.07), anti-HCV (OR,
      38.57; 95% CI, 18.15-81.96), and educational duration of less than 10 years (OR,
      1.71; 95% CI, 1.05-2.78) are independent risk factors of HCC. In addition, there
      was an additive interaction between betel quid chewing and chronic infection with
      either hepatitis B virus (synergy index, 5.37) or hepatitis C virus (synergy
      index, 1.66). Moreover, risk on HCC increased as duration of betel quid chewing
      increased, or amount of betel quid consumed (each P for trend < 0.0001).

PMID- 11237397
TI  - Oral contraceptives and colorectal cancer risk: a meta-analysis.
AB  - Several studies have suggested an inverse association between use of combined
      oral contraceptives (OC) and the risk of colorectal cancer and here we present a
      meta-analysis of published studies. Articles considered were epidemiological
      studies published as full papers in English up to June 2000 that included
      quantitative information on OC use. The pooled relative risks (RR) of colorectal
      cancer for ever OC use from the 8 case-control studies was 0.81 (95% confidence
      interval (CI): 0.69-0.94), and the pooled estimate from the 4 cohort studies was
      0.84 (95% CI: 0.72-0.97). The pooled estimate from all studies combined was 0.82
      (95% CI: 0.74-0.92), without apparent heterogeneity. Duration of use was not
      associated with a decrease in risk, but there was some indication that the
      apparent protection was stronger for women who had used OCs more recently (RR =
      0.46; 95% CI: 0.30-0.71). A better understanding of this potential relation may
      help informed choice of contraception.

PMID- 11237399
TI  - Unexpected increase in the bone marrow toxicity of mitomycin C (MMC).

PMID- 11237398
TI  - Diet, smoking and lung cancer: a case-control study of 1000 cases and 1500
      controls in South-West England.
AB  - We have examined the relationship between diet and lung cancer in a case-control
      study of 982 cases of lung cancer and 1486 population controls in south-west
      England in which subjects were interviewed personally about their smoking habits
      and their consumption of foods and supplements rich in retinol or carotene.
      Analyses were performed for 15 dietary variables, including intake of pre-formed
      retinol and carotene. There were significant associations (P< 0.01) with lung
      cancer risk for 13 of the variables, eight of which remained after adjustment for
      smoking. When the 15 variables were considered simultaneously, independent
      significant associations remained for 5: pre-formed retinol (increased risk), and
      fish liver oil, vitamin pills, carrots and tomato sauce (decreased risk). It is
      unlikely that all five associations represent biological effects, or that they
      can all be explained by residual confounding by smoking, or by biases. We
      conclude that there is at least one as yet unidentified factor that is causally
      related to lung cancer risk and of considerable importance in terms of
      attributable risk in this population.

PMID- 11237403
TI  - Cellular Ubuntu: 'umntu ngumntu ngabanye abantu', and other problems for cell
      biologists in the new millennium.

PMID- 11237404
TI  - Early development of the gut: new light on an old hypothesis.
AB  - This review deals with the early development of the gut. It draws largely on
      information provided from the study of avian embryos. Evidence that concerns the
      early determination of the regional fate of the endoderm and mesoderm of the gut
      is reviewed. Gut endoderm can undergo a limited degree of differentiation from a
      remarkably early age when cultured in the absence of mesoderm and there is
      evidence that points to the establishment of a pre-pattern in the early mesoderm
      before the genes responsible for patterning in gut are active. Initially, at
      least at cranial levels, those parts of the mesoderm and endoderm that are in
      contact are not those parts that will ultimately be in apposition; the
      consequence of this for any signalling between these layers is considered. In the
      light of the above information, the probable role of mesenchyme in gut
      development is re-examined.

PMID- 11237405
TI  - Regulation of gene expression by GC-rich DNA cis-elements.
AB  - GC-rich DNA cis elements are important transcriptional regulatory elements
      present in the promoter, enhancer and locus control regions of many eukaryotic
      genes from several species. This review attempts to examine the structure,
      function and biological significance of GC-rich cis -regulatory elements and
      their cognate binding proteins, with a view to understanding their role in
      regulation of gene expression.

PMID- 11237406
TI  - Thy-1 associated pp85--90 is a potential docking site for SH2 domain-containing
      signal transduction molecules.
AB  - Thy-1, a glycosylphosphatidylinositol (GPI)-anchored glycoprotein expressed at
      high levels on thymocytes, has been implicated in positive and negative signal
      transduction. We show that Thy-1 associates with a protein of 85--90 kDa, which
      is prominently phosphorylated in vitro as well as in vivo following the
      stimulation of thymocytes with pervanadate. pp85--90 is not identical to known
      proteins that are phosphorylated following T cell activation. The SH2 domains of
      fyn, csk, phosphatidylinositol 3'-kinase, rasGAP, vav and lck bind to pp85--90
      with varying affinities. The SH2 domains of ZAP70, SHP-1 and PLC gamma 1 and the
      SH3 domains of lck, vav and HS1 did not bind to pp85--90. The molecular weight,
      iso-electric point, efficient phosphorylation by fyn and lck and preferential
      binding to the SH2 domain of fyn compared to that of lck indicate that Thy-1
      associated pp85-90 may be identical to a recently cloned, fyn-associated
      transmembrane adaptor protein, PAG-85.

PMID- 11237407
TI  - Flow cytometric analysis of the Th1-Th2 balance in healthy individuals and
      patients infected with the human immunodeficiency virus (HIV) receiving a plant
      sterol/sterolin mixture.
AB  - The Th1--Th2 balance plays a pivotal role in determining the outcome of an immune
      response to an infectious organism. It is proposed that during HIV infection,
      disease progression is characterized by a loss of Th1 activity, a shift to a more
      'allergic' Th2-type response and hence loss of cytotoxic cell activity against
      infected host cells. This study was undertaken to investigate this balance in
      three groups of individuals: HIV-negative volunteers (n=10), a group of HIV
      infected patients on no therapy (n=10) as well as a group of patients managed
      with a mixture of plant sterols/sterolins (n=9). In parallel, their response to
      mitogens and the subsequent expression of the activation antigen CD69 was
      measured. This study was conducted by three-colour flow cytometry in order to
      obviate the less sensitive cytokine secretion assays that have yielded
      controversial results. The results indicate that HIV-infected patients on no
      therapy exhibit a pre-dominant Th2 response (IL-4 secretion), whereas those on
      the sterol/sterolin mixture exhibit a beneficial Th1 response (IFN-gamma).
      Surprisingly, in both patient groups, the expression of CD69 was abnormally low
      when compared to the uninfected volunteers, implying that chronic activation is
      already present in vivo. It appears that the detrimental Th2 driven response
      might be swung to the more beneficial Th1 response with the immune modulatory
      sterols/sterolin mixture. Clinical use of this mixture in HIV infection has
      yielded results which corroborate the above observations in that patients using
      the plant sterol/sterolin mixture maintain their CD4 cell numbers over an
      extended period of time in the absence of any anti-retroviral therapy.

PMID- 11237408
TI  - Assessment of the antitumour activity of targeted immunospecific albumin
      microspheres loaded with cisplatin and 5-fluorouracil: toxicity against a rodent
      ovarian carcinoma in vitro.
AB  - The 3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay is
      used successfully to estimate the number of viable cells in drug screening
      trials. We used the MTT assay to assess the viability of a rodent ovarian
      carcinoma cell line (DMBA-OC-1R) after exposure to combinations of cisplatin and
      5-fluorouracil as free drug and in encapsulated (conjugated and unconjugated)
      forms. After 48 h of exposure to free drugs, a significant trend towards cell
      cytotoxicity could be observed and this was well established by 120 h. Cells
      treated with drug-containing immuno-microspheres showed a similar initial
      decrease in cell viability after 96 h, and this was maintained for 128 h. These
      results suggest that immuno-microspheres loaded with chemotherapeutic drugs have
      the potential to be successfully used in the treatment of ovarian cancer.

PMID- 11237409
TI  - Environmental modulation of alpha(v), alpha(2) and beta(1) integrin subunit
      expression in human oesophageal squamous cell carcinomas.
AB  - Integrins are cell adhesion molecules pivotal in regulating normal cell
      behaviour. Ectopic expression of integrins, characteristic of transformed cells,
      is instrumental in differentiation, proliferation, apoptosis, angiogenesis,
      matrix degradation and migration. Oesophageal squamous cell carcinoma (SCC) has a
      propensity to metastasize and hence an extremely poor prognosis. It is shown here
      that oesophageal SCCs express alpha(v)strongly and that normal oesophageal tissue
      does not express alpha(v). This makes alpha(v)a significant indicator of the
      transformed phenotype. alpha(2)and beta(1)integrin subunits are down-regulated in
      oesophageal SCCs compared to normal oesophagus. Dominance of the
      alpha(2)beta(1)heterodimer is symptomatic of potential loss of other
      beta(1)binding integrins in oesophageal SCCs. These results suggest a decrease in
      rigid cell adhesion possibly increasing migratory potential, whilst
      simultaneously permitting the adhesion and migration of SCC cells on a large
      repertoire of ligands due to de novo alpha(v)expression.

PMID- 11237410
TI  - Mycobacterial growth in human macrophages: variation according to donor, inoculum
      and bacterial strain.
AB  - The microbicidal capacity of the macrophage is frequently evaded by mycobacteria,
      leading to tuberculosis (TB). We investigated a number of parameters affecting
      the rate of growth of mycobacteria in human monocyte-derived macrophages (MDM).
      The results show a great deal of variation in the growth of both Mycobacterium
      bovis BCG and M. tuberculosis H37Rv, using a large number of human macrophage
      donors, (132 and 40, respectively), but no correlation was seen with the TB
      status of the MDM donor. Clumping of the mycobacteria resulted in more vigorous
      growth in MDM, suggesting that inoculum size could affect disease progression.
      The growth rates of 17 clinical isolates of M. tuberculosis were measured in
      macrophages derived from three donors and no consistent or marked differences
      between isolates were observed over the 5-day period of growth measurement.
      However, all 17 clinical strains grew consistently faster than H37Rv in the same
      experiments.

PMID- 11237411
TI  - Diversity of in vitro cytokine responses by human macrophages to infection by
      mycobacterium tuberculosis strains.
AB  - Macrophages are an important component in the first line of defence of the innate
      immune system. They are capable of producing cytokines in response to bacterial
      challenge, as well as in response to cytokine stimuli from other cells in the
      immune system. The microbicidal response of human monocyte-derived macrophages in
      vitro, induced by exogenously added cytokines, is highly variable. We found that
      tumour necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony
      stimulating factor (GM-CSF) could have either stimulatory or inhibitory effects
      on intracellular BCG killing, depending on the macrophage donor. Macrophages
      infected in vitro by various clinical isolates of Mycobacterium tuberculosis or
      the laboratory strain H37Rv, produced varying levels of both TNF-alpha and IFN
      gamma. Certain M. tuberculosis strains tended to be associated with high cytokine
      production in each of three independent experiments, indicating that strains may
      differ in the host response elicited to infection.

PMID- 11237413
TI  - Effect of steroid hormones on membrane profiles of HeLa S3 cells.
AB  - The cervical carcinoma cell line, HeLa S3, was exposed to oestradiol and
      progesterone separately and combined in ratios similar to those of the luteal and
      follicular phases of the menstrual cycle. After 48 h of exposure, membrane
      proteins were extracted from the plasma membrane and analyzed. The lipid
      composition of the cells and lectin binding patterns to the cells were also
      assessed. The hormones had a profound effect on the HeLa S3 membrane protein
      profiles. Progesterone inhibited the synthesis of a wide variety of proteins
      while oestradiol negated this effect. Less variation between lipid profiles was
      noted although progesterone reduced the amount of cholesterol present.
      Differences in lectin binding profiles between the various treatments were noted,
      indicating an hormonal effect on glycosylation. Such hormonal effects on membrane
      composition may have implications in cervical susceptible to microbial
      infections.

PMID- 11237412
TI  - SV-40 large T antigen reversibly inhibits expression of tyrosinase, TRP-1, TRP-2
      and Mitf, but not Pax-3, in conditionally immortalized mouse melanocytes.
AB  - Transformation of mouse melanocytes with a variety of exogenous oncogenes or
      chemical carcinogens frequently results in irreversible loss of pigmentation. We
      have infected mouse melanocytes with a temperature-sensitive mutant of the simian
      virus 40 (SV40) large tumour antigen to study the molecular mechanisms underlying
      depigmentation during melanocyte transformation. The results show that, out of
      six cell lines analyzed at the permissive temperature of the oncoprotein, three
      epidermal and two dermal melanocyte clones remained pigmented and retained the
      ability to synthesize melanin and to express the melanocyte-specific genes,
      including tyrosinase, tyrosinase related protein-1, tyrosinase related protein-2
      and Mitf. In contrast, one dermal melanocyte clone (DMEL-3) gradually
      depigmented. This depigmentation was characterized by enhanced growth and down
      regulation of melanocyte-specific gene expression. When the oncogene was
      inactivated by culture at the non-permissive temperature, the pigmented phenotype
      in DMEL-3 cells could be rescued, and there was a corresponding time-dependent
      increase in melanocyte-specific gene expression. After extended passage, this
      rescue could not be achieved. Our results provide direct evidence for the role of
      the SV40 large T antigen in melanocyte de-differentiation. Expression of Pax-3, a
      transcription factor implicated in melanocyte differentiation, was unaltered
      during the SV40-initiated de-differentiation, and de-differentiated melanocytes
      expressed normal levels of Pax-3 message. We speculate on the mechanism by which
      the oncoprotein might be regulating Mitf gene expression and of the role of Pax-3
      in this process.

PMID- 11237414
TI  - Brief occlusion of the main pancreatic duct rapidly initiates signals which lead
      to increased duct cell proliferation in the rat.
AB  - In the course of investigating the signals associated with pancreas regeneration,
      we have developed a method to initiate pancreatic duct cell proliferation by
      brief occlusion of the main pancreatic duct. The resulting duct cell
      proliferation, induced by temporary partial main duct occlusion, was compared to
      that induced by firmly tying a cellophane strip around the head of the pancreas
      for longer periods of time. Both methods stimulated a biphasic increase in duct
      cell proliferation, with proliferation maxima at 3 and 14 days post operation.
      The short duration of temporary main duct occlusion (60 s) that was needed to
      stimulate duct cell proliferation, and the similar duct cell proliferation
      profiles that were observed after both the temporary and the longer term main
      duct occlusion, led us to conclude that the signals which initiate proliferation
      occur rapidly at the beginning of each procedure.

PMID- 11237415
TI  - Report of two international workshops on 'teaching and training in cell biology'.

PMID- 11237417
TI  - Fine structural modifications of liver, pancreas and brown adipose tissue
      mitochondria from hibernating, arousing and euthermic dormice.
AB  - An ultrastructural and morphometric study was performed on mitochondria of
      euthermic, hibernating and arousing hazel dormice (Muscardinus avellanarius), in
      order to investigate possible modifications during the seasonal cycle.
      Hepatocytes, pancreatic acinar cells and brown adipocytes were considered. Our
      results demonstrated that: (1) the general morphology of mitochondria of all cell
      types shows slight modifications during the seasonal cycle; (2) mitochondrial
      size and inner membrane length significantly increase from euthermia to
      hibernation and decrease upon arousal in all cell types; (3) mitochondrial matrix
      granules drastically increase in number during hibernation and decrease upon
      arousal in hepatocytes and pancreatic acinar cells, whereas they do not change in
      brown adipocytes. These structural modifications are probably related to the
      changes in cellular energy needs during the euthermia-hibernation-arousal cycle.

PMID- 11237418
TI  - Mosquito larvae proteins modulate luteinizing hormone and prolactin release in
      pituitary cells of normal and estrogenized rats.
AB  - Whilst looking for vertebrate growth factor homologues in insects, we found that
      a soluble fraction of a 12-80 kDa molecular weight band peaking at 25 kDa,
      isolated from mosquito larvae extracts by gel permeation chromatography, had a
      modulatory effect on mouse hepatocytes and adult human mononuclear cell
      proliferation. The effect disappeared after heating the extract at 90 degrees C
      for 30 min, suggesting that the active factor may be a protein. In order to
      determine the activity of the extract on cell function, we assessed the effect of
      the extract on pituitary hormone secretion in vitro. We assayed a dialyzed
      fraction (MW greater than 12 kDa) of mosquito larvae for its effect on the
      release of luteinizing hormone (LH) and prolactin (PRL) from dispersed rat
      pituitary cells. In normal anterior pituitary (AP) cells we found that the
      extract had a stimulatory effect on LH release but an inhibitory action on
      prolactin secretion. In AP cells obtained from estrogen-induced hyperplasia, the
      extract had an inhibitory effect on prolactin secretion. In all cases the effects
      were time- and dose-dependent. Interference of the mosquito proteins with the
      radioimmunoassay was checked and found to be negligible. After a 60 min
      incubation, cell viability was comparable in control and treated cells.
      Furthermore, the biological effect of the extract was thermally unstable. Our
      results suggest that mosquito larvae may share common factors with mammals,
      probably peptidic in nature, which are able to modulate cell function.

PMID- 11237416
TI  - Local regulation of anion secretion by pituitary adenylate cyclase-activating
      polypeptide in human colonic T84 cells.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a novel
      hypothalamic peptide, which has been shown to exert various functions in a number
      of tissues, including exocrine and endocrine tissues. The present study
      investigated the role of local PACAP in the control of anion secretion by the
      human colonic T84 cell. Both bioactive forms of PACAP-27 and PACAP-38 gave rise
      to a dose-dependent increase in the short-circuit current (I(SC)). However, there
      was a reversal in the order of potency observed at different concentration ranges
      for the two bioactive forms. PACAP-27 was greater than PACAP-38 when the peptide
      concentrations were below 10 n m; PACAP-38 was greater than PACAP-27 in the range
      of 10-80 n m. The effects of both PACAP forms were restricted to the apical
      aspect of the T84 cell. The I(SC)responses to both PACAP-27 and PACAP-38 were
      suppressed respectively by the non-selective Cl(-)channel blocker, diphenylamine
      dicarboxylic acid (DPC), by the Ca(2+)dependent Cl(-)channel blocker,
      diisothiocyanatostilbene-disulfonic acid (DIDS) and by the Ca(2+)chelator, BAPTA
      AM, indicating the involvement of Ca(2+). The expression of PACAP was
      demonstrated and localized specifically to the perinuclear cytoplasm of the T84
      cell using immunocytochemistry, indicating its epithelial origin. Thus, the
      present data suggest that, in addition to the well-known cAMP-dependent pathway,
      PACAP may play a role in regulating colonic Cl(-)secretion via a Ca(2+)-dependent
      pathway, perhaps through two distinct PACAP receptor subtypes. Moreover, the
      regulation of anion secretion by T84 cells may be mediated by locally formed
      PACAP in an autocrine or paracrine fashion.

PMID- 11237419
TI  - Giant vacuoles observed in Dictyostelium discoideum.
AB  - Large intracellular vacuoles, >4 microm in diameter and either round or oval
      shaped, were observed infrequently in Dictyostelium discoideum amoebae of
      axenically-grown strain AX2 (only 1 in 10(6)-10(8)cells). These previously
      unreported single or multiple 'giant' vacuoles were more common, however, in
      newly germinated KAX3 cells (0.55% of the population) and AT-K(neg), a strain
      that lacks an esterase (0.47% of the population). A vacuolar H(+)-ATPase was
      enriched in their membranes of intracellular giant vacuoles, indicating that the
      vacuoles were related possibly to both endosomes and the contractile vacuole
      compartment. When monitored over time, giant vacuoles protruded from, and
      retracted back into cells under hyperosmotic conditions, suggesting an
      osmoregulatory role for these vacuoles. Some of the intracellular and protruded
      giant vacuoles harbored a fluid-phase marker, fluorescein-labeled dextran,
      implying a pinocytotic origin for the vacuoles.

PMID- 11237420
TI  - Cytotoxicity of daunorubicin in trisomic (+21) human fibroblasts: relation to
      drug uptake and cell membrane fluidity.
AB  - The influence of daunorubicin (DNR) on survival of human normal (S-126) and
      trisomic, with respect to chromosome 21 (T-164; S-240), skin fibroblasts and some
      parameters related to it, such as intracellular drug accumulation, distribution
      and interaction with cell membrane, were studied. The in vitro growth-inhibition
      assay indicated that DNR was less cytotoxic for trisomic than for normal cells.
      Comparison of kinetic parameters and intracellular distribution of this compound
      showed that the uptake and the amount of intracellular free DNR were greater in
      normal than in trisomic cells. Contrary to this, there were no significant
      differences between the amount of DNA-bound drug in both types of cells. TMA-DPH
      and 12-AS fluorescence anisotropy measurements demonstrated that DNR decreased
      lipid fluidity in the inner hydrophobic region of plasma membrane in both cell
      types, but did not influence the fluidity of the outer surface of membrane. We
      conclude that fibroblasts derived from individuals affected with Down's syndrome
      are better protected from the damage induced by DNR than normal cells.

PMID- 11237421
TI  - Involvement of PI 3-kinase, PKA and PKC in PDGF- and TGF-beta-mediated prevention
      of 2-deoxy-D-ribose-induced apoptosis in the insect cell line, IPLB-LdFB.
AB  - Activation of phosphatidylinositol (PI) 3-kinase, protein kinase A (PKA) and
      protein kinase C (PKC) is associated with the survival effect elicited by PDGF-AB
      and TGF-beta1 against the apoptotic inducer 2-deoxy-D-ribose (dRib) in the fat
      body cell line, IPLB-LdFB, from the insect Lymantria dispar. dRib induces
      apoptosis and provokes mitochondrial membrane depolarization (MMD). The
      antioxidant N -acetyl-L-cysteine annuls only the first effect. These findings
      suggest that apoptosis and MMD are provoked by two different mechanisms, and that
      dRib induces apoptosis by oxidative stress.

PMID- 11237422
TI  - Circadian rhythm of DNA synthesis and mitotic activity in tongue keratinocytes.
AB  - Tongue keratinocytes have a high mitotic index (MI) with an evident circadian
      variation. Our study set out to compare and contrast two phases of the cell
      cycle: DNA synthesis (S-phase), with inmunocytochemical detection by
      bromodeoxyuridine (BrdU), and mitosis (M-phase), by the colchicine-arrest of
      metaphase method, exploring both the dorsal and ventral surfaces of the mouse
      tongue throughout a circadian period. Adult male mice standardized for light
      periodicity used for MI experiment were injected intraperitoneally with
      colchicine. Other animals were injected intraperitoneally with 5-BrdU for S-phase
      determination. Animals given both treatments were divided into six groups and
      killed at 4 h intervals until 20:00 h. Tongue samples were processed for
      histology and immuno-histochemistry. S and M indices were expressed as labelled
      nuclei or colchicine metaphases, respectively, per 1000 nuclei. Peak MI occurred
      at 12:00, with the minimum value at 20:00 on dorsal and ventral tongue surfaces.
      Peak S-phase was at 04:00, whereas the minimum value was at 16:00 for both
      surfaces. These results show that the proliferative activity of the tongue
      epithelium is of similar intensity and temporal distribution on both surfaces.

PMID- 11237423
TI  - Terminal differentiation of human promyelocytic leukaemia cells, HL-60, during
      the G1 period.
AB  - Human promyelocytic leukaemic cells, HL-60, arrested in mitosis by nocodazole
      were released in the presence of 1alpha,25-dihydroxyvitamin D3 and thymidine or
      hydroxyurea. Cells moved from early G1 period to the G1/S boundary and
      differentiated. Furthermore, cells arrested at the G1/S boundary by double
      thymidine block were released, with 1alpha,25-dihydroxyvitamin D3 being added at
      the end of DNA synthesis. Under the latter conditions, differentiated cells
      developed, indicating that DNA synthesis is not required for cell
      differentiation.

PMID- 11237426
TI  - Enhancement of T helper2 response in the absence of interleukin (IL-)6; an
      inhibition of IL-4-mediated T helper2 cell differentiation by IL-6.
AB  - Functional roles of interleukin (IL-)6 in T cell response were investigated. Mice
      deficient in IL-6 and wild mice were immunized with antigens (myelin
      oligodendrocyte glycoprotein or methylated BSA) and production of IL-4 and
      interferon (IFN)-gamma by regional lymph nodes was measured. IL-6 deficiency led
      to an enhancement of IL-4 and an inhibition of IFN-gamma production. Moreover,
      polyclonal stimulation of spleen T cells from unimmunized IL-6-deficient mice
      with anti-CD3 plus anti-CD28 antibodies (Abs) demonstrated an enhancement of T
      helper (Th)(2)responses. The presence of IL-6, however, augmented IL-4 production
      but it inhibited IFN-gamma expression by spleen T cells in response to polyclonal
      stimulation and by antigen-primed spleen T cells in response to re-challenge with
      the antigen. In contrast, the induction of spleen CD4-positive T cells into
      Th(2)cells in vitro by the anti-CD3 plus IL-4 was completely suppressed by
      exogenously added IL-6, whereas Th(1)differentiation of T cells by the anti-CD3
      plus IL-12 was not inhibited by the presence of IL-6. Thus, these results
      indicate that IL-6 physiologically could modulate qualitative T cell response and
      suggest that it augments Th(1)responses partly through its inhibitory capability
      of IL-4-induced Th(2)differentiation of naive T cells.

PMID- 11237427
TI  - Flt3 ligand pretreatment promotes protective immunity to Listeria monocytogenes.
AB  - Flt3 ligand (Flt3L) plays a critical role in the proliferation, differentiation
      and survival of haematopoietic progenitor cells. Its potential use in a clinical
      setting has been suggested. Here, we report that mice administered Flt3L
      displayed a nine-fold increase in size of their hepatic non-parenchymal cell
      population and an approximate 365-fold increase in number of mature dendritic
      cells within their livers. Such mice exhibited an elevated resistance to
      secondary infections with Listeria monocytogenes, an intracellular bacterial
      pathogen. More than 2.0 log(10)fewer listeriae were recovered in the livers of
      Flt3L-treated, than untreated, mice on day 2 following secondary challenge.
      Importantly, Flt3L-pretreated mice immunized with an avirulent (listeriolysin O
      negative) strain of Listeria harbored significantly fewer ( approximately 1.5
      log(10)) organisms in their spleens and livers than did control mice immunized
      with listeriolysin O-negative listeriae and challenged with a lethal dose of
      bacteria. The latter finding supports a potential role for Flt3L in strategies to
      develop vaccines to intracellular pathogens.

PMID- 11237428
TI  - Analysis of eosinophils and myeloid progenitor responses to modified forms of
      MPIF-2.
AB  - Myeloid progenitor inhibitory factor (MPIF)-2 is a beta-chemokine with select and
      potent activities on eosinophils and myeloid progenitors. In the beta-chemokine
      family, biological activity is modulated by differential processing of the amino
      terminus. Here, for MPIF-2, we describe the biological activities of NH(2)
      terminal deletion mutants and compare regions necessary for eosinophil and
      myeloid progenitor activities. Five MPIF-2 proteins with deletions at the amino
      terminus were produced in Escherichia coli and assayed for calcium mobilization,
      chemotaxis and receptor binding activities on eosinophils, and for their ability
      to inhibit colony formation of human myeloid bone marrow progenitors. For
      eosinophils, deletion of the first two amino acids did not markedly alter
      activity, while subsequent truncations result in a complete loss of activity. One
      of the MPIF-2 mutants, MPIF-2 (P30-R99) was converted from an agonist to an
      antagonist of eotaxin, MPIF-2 and MCP-4 functional responses in eosinophil
      calcium flux and chemotaxis assays. Surprisingly, while displaying a complete
      loss of agonist activity toward eosinophils, MPIF-2 (P30-R99) retains ability to
      inhibit human bone marrow myeloid progenitor cell colony formation. In addition,
      processing at the amino terminus of MPIF-2 in vivo, may result in a chemokine
      with altered biological activities.

PMID- 11237429
TI  - Establishment and characterization of a human B cell line from the lung tissue of
      a patient with scleroderma; extraordinary high level of IL-6 secretion by
      stimulated fibroblasts.
AB  - Progressive systemic sclerosis is a connective tissue disease of unknown
      aetiology. This is the first study to demonstrate induction by a human B cell
      line of IL-6 secretion from fibroblasts. The cell line was established from
      lesional lung tissue of a patient with progressive systemic sclerosis. These
      cells, referred to as kon-1 cells, showed characteristics of pro-B cell by flow
      cytometry. Although kon-1 cells alone secreted a small amount of IL-6, a co
      culture of kon-1 cells with normal lung fibroblasts significantly increased IL-6
      levels. Whereas IL-6 mRNA was weakly expressed in kon-1 cells alone, it was
      clearly expressed in cells from the co-culture. Immunocytochemical identification
      of IL-6 showed localization in the cytoplasm of fibroblasts. IL-6 is a
      pleiotropic cytokine, essential for B cell differentiation, which has been shown
      to stimulate the production of collagen and glycosaminoglycan. Thus, abnormally
      augmented B cell proliferation and the inflammatory response stimulated by these
      cells may cause the fibrotic changes in patients with progressive systemic
      sclerosis.

PMID- 11237430
TI  - Quantification and in situ localization of MCP-1 mRNA and its relation to the
      immune response of renal cell carcinoma.
AB  - Malignant tumours are usually accompanied by an immune response. Chemokines such
      as MCP-1 have been claimed to be potent inducers of such tumour-associated
      reactions. In the present study MCP-1 mRNA was quantified by competitive reverse
      transcription polymerase reaction and localised by in situ hybridisation in renal
      cell carcinoma tissue in comparison to tumour-free tissue of the same nephrectomy
      specimen. MCP-1 mRNA levels were correlated with the immune cell infiltrate, the
      density of CD31(+)microvessels, and the endothelial expression of ICAM-1, VCAM-1,
      E-, and P-selectin. In only seven of 19 cases, MCP-1 mRNA levels in carcinoma
      tissue were increased in comparison to tumour-free tissue. Within tumour tissue,
      mRNA transcripts could be localised in tumour cells, microvessel endothelia, and
      in tumour-associated macrophages. A correlation between MCP-1 mRNA levels and the
      density of immune cells, especially macrophages, the microvessel density, and the
      expression of adhesion molecules could not be observed. Therefore, MCP-1 seems to
      be of minor importance for the induction of an immune response in renal cell
      carcinomas regarding at least the parameters analysed in this study.

PMID- 11237431
TI  - Mediators of fetal inflammation in extremely low gestational age newborns.
AB  - To establish levels of mediators of inflammation in cord blood and postnatal
      serum from extremely low gestational age newborns (ELGANs, < or =28 weeks), we
      measured sixteen markers of inflammation by recycling immunoaffinity
      chromatography in 15 ELGANs who had serum sampled at days 2-5. Median levels of
      IL-1, IL-6, IL-8, IL-11, IL-13, TNF-alpha, G-CSF, M-CSF, GM-CSF, MIP-1alpha, and
      RANTES were considerably higher than published values of these inflammatory
      mediators from term newborns. In three of eight ELGANS who had serial
      measurements taken, levels of IL-1, IL-6, IL-8, IL-11, TNF-alpha, G-CSF, and MIP
      1alpha declined from initially very high levels to reach an apparent baseline
      towards the end of the first postnatal week. In these same three infants, GM-CSF
      and TGF-beta1 levels increased continuously during the first week. In the other
      five ELGANs, no consistent changes were observed. We speculate, that in some
      ELGANs, a fetal systemic inflammatory response is characterized by an antenatal
      wave of pro-inflammatory cytokines, followed by a second, postnatal wave of anti
      inflammatory cytokines. Large epidemiologic studies are needed to clarify
      relationships among inflammation markers and their expression in the fetal and
      neonatal circulation over time. Such studies would also add to our understanding
      of the possible role of inflammatory mediators in the pathophysiology of the
      major complications of extreme prematurity.

PMID- 11237432
TI  - GM-CSF binding to its receptor induces oligomerisation of the common beta
      subunit.
AB  - The stoichiometry of the granulocyte-macrophage colony-stimulating factor (GM
      CSF) receptor complex is still unresolved. We have utilised a sensitive,
      functional assay for receptor homodimerisation to show that GM-CSF induces
      dimerisation of the common signalling subunit, hbeta(c). We generated a chimeric
      cytokine receptor in which the extracellular and transmembrane domains of
      hbeta(c)are fused to the cytoplasmic domain of erythropoietin receptor (EPO-R).
      Given that to induce EPO-R activation and mitogenic signalling there is a
      requirement for formation of a specific homodimeric complex, we reasoned that the
      cytoplasmic domain of EPO-R could be utilised as a highly sensitive reporter for
      functional homodimer formation. We show that, in the presence of a
      cytoplasmically truncated GM-CSF alpha-subunit, the hbetac-EPO receptor chimera
      transduces a mitogenic signal in BaF-B03 in response to GM-CSF. This is
      consistent with formation of a hbeta(c)homodimer following GM-CSF binding and
      implies that ligand stimulation induces formation of a higher order complex that
      contains the hbeta(c)homodimer.

PMID- 11237433
TI  - Interleukin 15 stimulates production of matrix metalloproteinase-9 and tissue
      inhibitor of metalloproteinase-1 by human peripheral blood mononuclear cells.
AB  - In peripheral blood mononuclear cells (PBMC), matrix metalloproteinase (MMP)-9
      mediates the extravasation of immune cells and may be involved in tissue
      destruction during inflammation. We investigated the effect of the pro
      inflammatory cytokines interleukin (IL-)12 and 15 on the secretion of MMP-9 in
      PBMC. IL-15, but not IL-12, induces MMP-9 in PBMC and in T cells. Moreover, the
      combination of IL-15 and IL-2 had an additive effect. In contrast, both IL-12 and
      IL-15 induced the release of tissue inhibitor of metalloproteinases (TIMP)-1. IL
      15 led to a dose-dependent increase of the MMP-9/TIMP-1 ratio as a measure for
      increased proteolytic capacity. We conclude that IL-15 mediates its effects in
      inflammation in part through MMP-9.

PMID- 11237434
TI  - Imbalance of IL-2, IFN-gamma and IL-10 secretion in the immunosuppression
      associated with human paracoccidioidomycosis.
AB  - Patients with paracoccidioidomycosis (PCM) display a certain degree of
      immunecompromise characterized by lymphocyte hyporesponsiveness to the main
      Paracoccidioides brasiliensis antigen (gp43). To determine whether cytokines are
      involved in this state, we evaluated the secretion of IL-2, IL-10 and IFN-gamma
      by peripheral blood mononuclear cells (PBMC) from patients with the acute (AF)
      and chronic (CF) forms of PCM and from healthy, P. brasiliensis-sensitized
      subjects. gp43-stimulated PBMC from healthy subjects produced substantial amounts
      of IL-2, IFN-gamma and IL-10, whereas PBMC from AF and CF patients produced low
      levels of IL-2 and IFN-gamma but substantial amounts of IL-10.
      Phytohaemagglutinin-induced cytokine secretion was comparable among AF and CF
      patients and healthy subjects, suggesting integrity of non-specific cellular
      immune mechanisms in PCM. gp43-pulsed adherent cells, but not non-adherent cells,
      were the main source of IL-10. Moreover, IL-2 and IFN-gamma secretion correlated
      inversely with the amount of specific antibodies produced by patients and healthy
      subjects. Our results suggest that the imbalance in cytokine production of
      patients with PCM plays a role in the gp43-hyporesponsiveness and the marked (non
      protective) antibody production of these patients.

PMID- 11237435
TI  - C-reactive protein and interleukin 6 receptor in post-traumatic stress disorder:
      a pilot study.
AB  - BACKGROUND: it has been reported that psychological stress in humans is
      associated with a derangement of biological homeostasis. This pilot study aimed
      to examine the inflammatory response to post-traumatic stress disorder (PTSD)
      through measurements of the serum levels of the receptor to interleukin 6 (sIL
      6r) and C-reactive protein (CRP), in relation to measures of psychological
      disturbance. METHODS: 15 patients with established PTSD and eight control
      patients with musculoskeletal injuries were studied at least three months after
      their index trauma. All completed revised impact of events scale (RIES),
      Davidson's trauma scale (DTS) and the general health questionnaire (GHQ), and
      gave blood samples that were assayed for CRP and sIL-6r. Statistical analysis was
      by the Mann-Whitney U-Wilcoxon rank sum tests. RESULTS: positive relationships
      were found between sIL-6r and the RIES intrusion score (P=0.026), and between CRP
      and DTS intrusion scores (P=0.016), GHQ depression (P=0.028), and RIES intrusion
      (P=0.044) in the case group. DISCUSSION: we have demonstrated a relationship
      between post-traumatic psychological and biological disturbance, which provides
      the basis for further research on the effects of psychological disturbance on
      physical recovery after injury.

PMID- 11237436
TI  - Studies on the Binary Coalescence Model.
AB  - The jumping coalescence phenomenon between two separate water drops under
      microgravitation was observed for the first time. Two suspended water drops
      separated by quite a distance (0.558 mm) coalesce in a certain time (158 s)
      without any extra forces. The coalescence driving force within the water drops
      should be responsible for the jumping coalescence phenomenon. Copyright 2001
      Academic Press. 

PMID- 11237437
TI  - Nanocrystalline Domain Identification in Gold Films, by Backscattered Electron
      Imaging and Energy-Filtered Transmission Electron Microscopy.
AB  - Gold nanocrystallites dispersed in an inhomogeneous gold matrix are detected by
      high-resolution scanning electron microscopy using a field emission source and
      backscattered electron detection in the composition mode, as well as by energy
      filtered transmission electron microscopy in the plasmon energy region. The
      identity of the nanocrystalline domains was established by observing the same
      evaporated gold film samples but using bright-field, dark-field, electron
      diffractogram, and electron energy loss spectroscopy images in the transmission
      electron microscope. Comparison of these images shows that backscattered electron
      and plasmon energy detection can be used to identify crystalline domains in an
      otherwise chemically uniform sample. Copyright 2001 Academic Press. 

PMID- 11237438
TI  - Synthesis of Barium Ferrite Ultrafine Particles by Coprecipitation in the
      Presence of Polyacrylic Acid.
AB  - The barium ferrite ultrafine particles were synthesized by coprecipitation in an
      aqueous solution with polyacrylic acid (PAA) as a protective agent. Thermal
      analysis by TGA/DTA showed that the precursor could yield barium ferrite after
      calcination above 700 degrees C for 2 h. By analyses of the XRD and electron
      diffraction pattern, the formation of pure barium ferrite was confirmed and the
      appropriate molar ratio of Ba/Fe in aqueous solution was determined to be 1/11.
      The TEM measurements indicated that the average diameter of the precursor was 4.5
      nm, and the diameters of the particles calcined at 700 and 800 degrees C were 23
      34 and 49-82 nm, respectively. The magnetic properties characterized by a SQUID
      magnetometer showed that the barium ferrite ultrafine particles calcined at 700
      800 degrees C had a saturation magnetization of 36.9-60.8 emu/g, a remanent
      magnetization of 19.0-31.0 emu/g, a coercivity of 117.3-221.8 Oe, and a
      squareness ratio of 0.51. The magnetization was also observed to increase with a
      decrease of temperature at 5-400 K. These magnetic properties all reflected the
      nature of ultrafine particles and also were influenced by the morphology and
      microstructure of final products. Copyright 2001 Academic Press. 

PMID- 11237439
TI  - Surface Complexation Modeling and FTIR Study of Carbonate Adsorption to Goethite.
AB  - Experimental data for carbonate adsorption onto synthetic goethite, spanning 3
      orders of magnitude in carbonate concentrations, were simulated using the triple
      layer surface complexation model (TLM). A single set of TLM parameters
      successfully described the adsorption behavior versus pH over the concentration
      range obtained from closed and open CO(2) conditions. An optimization analysis
      was performed for all possible interfacial charge configurations using FITEQL3.2.
      The results yielded an optimum charge allocation of 0 and -1 in the 0- and beta
      planes, respectively, which suggests a monodentate complex most probably in an
      inner-sphere configuration (SOCOO(-beta)). Fourier transform infrared (FTIR)
      spectroscopic measurements on open systems at atmospheric P(CO(2)) confirmed this
      result by showing a clear peak split (155 cm(-1)) of the nu(3) C-O asymmetric
      stretching frequency of surface-bound carbonate, consistent with that reported
      for monodentate Co(III)-carbonato inner-sphere solution complexes. An additional
      Na(+)-ternary complex (SOCOONa) was invoked in the TLM construct to improve
      simulations of the enhanced carbonate adsorption occurring at high ionic strength
      and high pH. The model was successful in predicting carbonate adsorption behavior
      under diffferent conditions than it was calibrated for. Projections for
      equilibration at higher P(CO(2))'s (1-10%) than those used in this work show the
      potential for carbonate sorption densities of up to 2.5-3 umol/m(2). Copyright
      2001 Academic Press. 

PMID- 11237440
TI  - Vesicle Phases with Semipolar Additives.
AB  - We examined the influence of semipolar additives on the phase behavior of mixed
      zwitterionic surfactant/consurfactant systems. It is shown that in these systems
      with increasing concentration esters like hexylacetate (HA) and ketones like
      hexylmethylketone (HMK) can behave both like consurfactants and like
      hydrocarbons. In solutions of 200 mM tetradecyldimethylamineoxide
      (TDMAO)/cosurfactant the additives cause first a phase transformation from the
      micellar L(1) phase to a lamellar L(alpha) phase. Upon further increasing
      concentration, the L(alpha) phase is transformed into a microemulsion. The
      L(alpha) phase consists of densely packed multilamellar vesicles. The vesicles
      are shown by electron microscopy. The multilamellar character of the vesicles is
      also reflected in the conductivity of the phase. It is up to 10 times lower than
      the conductivity of the L(1) phase. In some systems the vesicles are transformed
      on rest into a multidomain stacked L(alpha) phase. It is furthermore demonstrated
      that the two-phase L(1)/L(alpha) region in these systems is very narrow. In
      situations where enough HA is added to be close to the boundary of the L(1)
      phase, it is shown that very small amounts of cosurfactant can transform the L(1)
      phase into the L(alpha) phase. In extreme situations 1 mM cosurfactant is
      sufficient for transforming the L(1) phase with 200 mM TDMAO into the L(alpha)
      phase. In the investigated systems the L(alpha) phase is a highly viscoelastic
      fluid in which the storage modulus is 1 order of magnitude larger than the loss
      modulus. Besides the conventional way to prepare samples by adding all
      ingredients and stirring the solution intensively, all investigated systems were
      additionally prepared without applying any shear forces. In a
      surfactant/cosurfactant solution the additive was brought into the sample by
      diffusion. The phase behavior of both types of samples showed fundamental
      differences in some cases, which give insight into the influence of shear forces
      on these systems. Copyright 2001 Academic Press. 

PMID- 11237441
TI  - On the Interfacial Deformation of a Magnetic Liquid Drop under the Simultaneous
      Action of Electric and Magnetic Fields.
AB  - The influence of uniform constant magnetic and electric fields, acting
      simultaneously, on a magnetic fluid drop is theoretically investigated. The drop
      is suspended in another magnetic fluid that is immiscible with the former. Both
      fluids are regarded as incompressible, viscous, weakly electrically conducting,
      polarizable, and magnetizable. The relative orientation of electric and magnetic
      intensity vectors is arbitrary. The equation for the surface of the drop is
      obtained in the approximation of small distortion of the drop. It is shown that
      the surface is an ellipsoid whose semiaxes can be expressed in terms of the
      intensity vectors of the electric and magnetic fields. The relations determining
      the orientation of its principal axes are also obtained. Copyright 2001 Academic
      Press. 

PMID- 11237442
TI  - Microstructure and Ion Exchange in Stearic Acid Langmuir-Blodgett Films Studied
      by Fourier Transform Infrared-Attenuated Total Reflection Spectroscopy.
AB  - Fourier transform infrared-attenuated total reflection (FTIR-ATR) spectra have
      been recorded of 11-layer Langmuir-Blodgett (LB) films of stearic acid deposited
      at various surface pressures (0.1, 15, and 35 mN/m), and the molecular
      orientation angles were evaluated quantitatively, which supplied insight into the
      molecular order with the alkyl chains tightly packed like crystal in the LB films
      deposited at the zero and higher surface pressures. These experimental results
      indicate that, in the Langmuir film as the precursor of LB films, stearic acid
      molecules self-aggregate to form two-dimensional crystalline domains already even
      at the zero surface pressure, which results in the inhomogeneity of monolayer.
      The analysis of dependence of nu(C=O) intensity on the surface pressure, surface
      density, and subphase temperature leads to the conclusion that the defects in LB
      films originate from the Langmuir film and be conserved upon deposition.
      Annealing below 50 degrees C and cooling could improve the monolayer homogeneity,
      and thus a defect-free or low-defect LB films can be deposited. Furthermore, ion
      exchange conducted in the LB films, on the other hand, confirms the existence of
      structure defects in LB films of stearic acid. The polar plane microstructure,
      lateral transport along the polar planes and the coordination types of stearic
      acid/cation system may be the rate-limiting process. The results have implication
      on the possible uses of stearic acid LB films as ion-exchange materials or
      sensors. Copyright 2001 Academic Press. 

PMID- 11237443
TI  - Preparation and Defluorination Performance of Activated Cerium(IV) Oxide/SiMCM-41
      Adsorbent in Water.
AB  - By using the wetness impregnation-coprecipitation method, a new adsorbent,
      cerium(IV) oxide coated on SiMCM-41 ((Ce)SiMCM-41), was prepared for removal of
      fluoride ions from water. Factors investigated were number of impregnations,
      Ce/Si ratios, concentrations of F(-) ions, pH values, and calcination
      temperatures. The dynamics, isotherms, and mechanism of adsorption of F(-) ions
      were discussed. Copyright 2001 Academic Press. 

PMID- 11237444
TI  - Protein Adsorption onto Zirconia Modified with Terminally Grafted
      Polyvinylpyrrolidone.
AB  - The potential effectiveness of poly(vinyl pyrrolidone) (PVP) as a zirconia
      surface modifier for protein adsorption reduction was investigated using lysozyme
      (LYS). The relatively small size of LYS (45 x 30 x 30 A) allowed for testing the
      adequacy of the graft polymerization method for producing a dense surface chain
      coverage to exclude LYS from direct interaction with the zirconia surface. The
      study demonstrated that a PVP brush layer is capable of reducing lysozyme
      adsorption. Overall, the maximum adsorption capacity decreased (by up to about
      76%) due to surface modification with increasing polymer/silane surface coverage
      ratio (mol/mol). Adsorption reduction, due to protein exclusion from the surface
      by the tethered polymer layer, increased significantly when the distance between
      surface chains was less than the large axis of LYS (i.e., 45 A). The present
      results are encouraging and suggest further consideration of polymer-modified
      ceramic surfaces for reducing fouling of ceramic membranes during protein
      ultrafiltration and producing ceramic biocompatible surfaces for biomedical
      applications. Copyright 2001 Academic Press. 

PMID- 11237445
TI  - X-ray Absorption Spectroscopic Investigation of Arsenite and Arsenate Adsorption
      at the Aluminum Oxide-Water Interface.
AB  - We investigated the As(III) and As(V) adsorption complexes forming at the gamma
      Al(2)O(3)/water interface as a function of pH and ionic strength (I), using a
      combination of adsorption envelopes, electrophoretic mobility (EM) measurements,
      and X-ray absorption spectroscopy (XAS). The As adsorption envelopes show that
      (1) As(III) adsorption increases with increasing pH and is insensitive to I
      changes (0.01 and 0.8 M NaNO(3)) at pH 3-4.5, while adsorption decreases with
      increasing I between pH 4.5 and 9.0, and (2) As(V) adsorption decreases with
      increasing pH and is insensitive to I changes at pH 3.5-10. The EM measurements
      show that As(III) adsorption does not significantly change the EM values of gamma
      Al(2)O(3) suspension in 0.1 M NaNO(3) at pH 4-8, whereas As(V) adsorption lowered
      the EM values at pH 4-10. The EXAFS data indicate that both As(III) and As(V)
      form inner-sphere complexes with a bidentate binuclear configuration, as
      evidenced by a As(III)-Al bond distance of congruent with3.22 A and a As(V)-Al
      bond distance of congruent with3.11 A. The As(III) XANES spectra, however, show
      that outer-sphere complexes are formed in addition to inner-sphere complexes and
      that the importance of outer-sphere As(III) complexes increases with increasing
      pH (5.5 to 8) and with decreasing I. In short, the data indicate for As(III) that
      inner- and outer-sphere adsorption coexist whereas for As(V) inner-sphere
      complexes are predominant under our experimental conditions. Copyright 2001
      Academic Press. 

PMID- 11237446
TI  - The Viscosity of Solutions of Poly(propylene imine) Dendrimers in Methanol.
AB  - The viscosity of solutions of poly(propylene imine) dendrimers in methanol has
      been determined. An Ubbelohde and a low-shear rotational viscometer have been
      used. The viscosity was Newtonian for every concentration and shear rate used.
      The value of the Huggins coefficient indicates soft sphere behavior. The
      viscosity of the lower generations as a function of the volume fraction can be
      described with a single exponent, where the exponent is comparable to the
      intrinsic viscosity. The viscosity of the 4th and 5th generation dendrimers shows
      a stronger increase from a volume fraction of about 0.15 to 0.30. This increase
      is much smaller than that expected, using the Krieger-Dougherty formula for hard
      spheres with the hydrodynamic radius determined from the intrinsic viscosity.
      This smaller increase and the small value of the Huggins coefficient are
      interpreted in terms of a breakdown of the solvation layer. At a volume fraction
      of 0.3 the dendrimers, using the radius of gyration as the radius, start to touch
      each other. From the dependence of the viscosity on the concentration and the
      dependence of the viscosity on the molar weight, it can be concluded that
      dendrimers do not interpenetrate. It is concluded that they deform (collapse).
      Copyright 2001 Academic Press. 

PMID- 11237447
TI  - Kaolin-Carbon Adsorbents for Carotene Removal of Red Palm Oil.
AB  - Kaolin-carbon adsorbents were prepared with and without sulfuric acid
      pretreatment followed by activation-carbonization at 500 degrees C. The total
      surface area of the resulting kaolin-carbon adsorbents was found to be decreased
      with the increase in kaolin loading. Sulfuric acid pretreatment of the precursor
      prior to the carbonization-activation processes resulted in the enhancement of
      total surface area but reduced the micropore surface area of the resulting
      adsorbents. At the same time, this improved carotene adsorption capacity from red
      palm oil. However, recovery of carotene from the carotene-adsorbed adsorbent is
      only improved when the acid pretreatment of the precursor was done at a high
      loading percentage of activated carbon. Similarly, the peroxide value (PV)
      increased. A maximum removal of carotene from red palm oil was obtained at 20%
      kaolin loading for both adsorbents prepared with and without sulfuric acid
      pretreatment with about 45 and 65% carotene removal, respectively, from a 30-ppm
      solution. This indicates that pretreatment with sulfuric acid, prior to the
      activation-carbonization process, increased the carotene uptake by the resulting
      adsorbent. However, a further increase in the kaolin loading resulted in the
      decrease of carotene removal. About 3-4% of carotene adsorbed can be recovered
      from both types of adsorbents under optimum condition, in which the percentage
      recovered decreased with the increase in kaolin loading. On the other hand, the
      PV increased with kaolin loading at around 54-64 mEq/kg for both types of
      adsorbents. It was also found that carotene uptake by the adsorbents is high if
      the adsorbent contains a high percentage of activated carbon. Similarly, carotene
      recovery is high and less oxidation can be observed, as indicated by the lower PV
      value. Copyright 2001 Academic Press. 

PMID- 11237448
TI  - Spontaneous Penetration of Liquids into Capillaries and Porous Membranes
      Revisited.
AB  - A critical review of the problem of spontaneous penetration of a wetting liquid
      into pore channels shows that no theory exists to quantitatively predict the
      initial stage of imbibition. Since C. H. Bosanquet (1923, Phil. Mag. 45, 525),
      the theory operates with an universal velocity U(Bosanquet)=(2gammacosstraight
      thetarhor(1/2), with gamma being the surface tension, straight theta the contact
      angle, r the capillary/pore radius, and rho the fluid density. It is assumed that
      the initial impulse of the liquid entering the pore is insignificant for the
      penetration dynamics. Though the importance of the outside flow pattern has been
      noted in many papers, a thorough mathematical analysis of this effect is lacking
      in the literature. We derived a generalized equation of the fluid front motion by
      averaging the Euler equations of flow inside and outside the pore space. This
      analysis shows the significance of the flow patterns at the pore entrance. The
      initial stage of liquid imbibition is studied in the inviscid approximation using
      the methods of dynamic systems. The phase portrait of the dynamic system reveals
      a multiplicity of penetration regimes. Remarkably, the Bosanquet solution
      represents a particular regime, with the apparent mass being set zero. The
      Bosanquet trajectory refers to a separatrix of the phase portrait. It is shown
      that the initial conditions affect the rate of uptake significantly. The initial
      conditions stem from the prehistory of the fluid motion outside the pores prior
      to the liquid-solid contact. The phase portrait method allows us to distinguish
      two groups of solutions for the capillary rise dynamics of an inviscid fluid. The
      first group of trajectories corresponds to the liquid front rebound; the second
      group includes cyclic trajectories which correspond to the periodic regimes with
      liquid front oscillations at the equilibrium position. The upper estimate of the
      oscillation amplitude is found. Copyright 2001 Academic Press. 

PMID- 11237449
TI  - Metallomicellar Catalysis Cleavage of p-Nitrophenyl Picolinate Catalyzed by
      Binuclear Metal Complexes Coordinating Tripeptide in CTAB Micellar Solution.
AB  - The catalytic hydrolysis of p-nitrophenyl picolinate (PNPP) by Cu(II) and Zn(II)
      complexes coordinating tripeptide were studied kinetically by observing the rates
      of release of p-nitrophenol in the buffered micellar solution at 25 degrees C and
      different pH values. The experimental results indicate that 1 : 2 ligand : metal
      ion complexes in CTAB micellar solution are the active species in the reaction,
      and the complexes, especially that with Cu(II), efficiently catalyze the
      hydrolysis of PNPP. As a result, a kinetic model of binuclear metal complex
      catalysis involving a ternary complex in CTAB micellar solution is proposed to
      analyze the kinetic behavior of catalysis, and thus, relative kinetic and
      thermodynamic parameters are obtained. The results predict that the catalytic
      reaction by metallomicelle with binuclear complex involves a bifunctional
      mechanism. Copyright 2001 Academic Press. 

PMID- 11237450
TI  - Mixed Micellization of Dimeric (Gemini) Surfactants and Conventional Surfactants.
AB  - The aqueous solutions of mixtures of various conventional surfactants and dimeric
      anionic and cationic surfactants have been investigated by electrical
      conductivity, spectrofluorometry, and time-resolved fluorescence quenching to
      determine the critical micelle concentrations and the micelle aggregation numbers
      in these mixtures. The following systems have been investigated: 12-2-12/DTAB, 12
      2-12/C(12)E(6), 12-2-12/C(12)E(8), 12-3-12/C(12)E(8), Dim3/C(12)E(8), and
      Dim4/C(12)E(8) (12-2-12 and 12-3-12=dimethylene-1,2- and trimethylene-1,3
      bis(dodecyldimethylammonium bromide), respectively; C(12)E(6) and C(12)E(8)=hexa-
      and octaethyleneglycol monododecylethers, respectively; Dim3 and Dim4=anionic
      dimeric surfactants of the disodium sulfonate type, Scheme 1;
      DTAB=dodecyltrimethylammonium bromide). For the sake of comparison the
      conventional surfactant mixtures DTAB/C(12)E(8) and SDS/C(12)E(8) (SDS=sodium
      dodecylsulfate) have also been investigated (reference systems). Synergism in
      micelle formation (presence of a minimum in the cmc vs composition plot) has been
      observed for the Dim4/C(12)E(8) mixture but not for other dimeric
      surfactant/nonionic surfactant mixtures investigated. The aggregation numbers of
      the mixed reference systems DTAB/C(12)E(8) and SDS/C(12)E(8) vary monotonously
      with composition from the value of the aggregation number of the pure C(12)E(8)
      to that of the pure ionic component. In contrast, the aggregation number of the
      dimeric surfactant/C(12)E(8) mixtures goes through a minimum at a low value of
      the dimeric surfactant mole fraction. This minimum does not appear to be
      correlated to the existence of synergism in micelle formation. The initial
      decrease of the aggregation number of the nonionic surfactant upon addition of
      ionic surfactant, up to a mole fraction of ionic surfactant of about 0.2 (in
      equivalent per total equivalent), depends little on the nature the surfactant,
      whether conventional or dimeric. The results also show that the microviscosity of
      the systems containing dimeric surfactants is larger than that of the reference
      systems. Copyright 2001 Academic Press. 

PMID- 11237451
TI  - Preparation of Water-Repellent Glass by Sol-Gel Process Using
      Perfluoroalkylsilane and Tetraethoxysilane.
AB  - Coating films on glass substrate were prepared by sol-gel process using alkoxide
      solutions containing perfluoroalkylsilane (PFAS) and tetraethoxysilane (TEOS).
      The physical properties of the coating films were characterized by SEM, FT-IR,
      and XRD. And their surface properties were investigated by measuring contact
      angles and atomic compositions. Transparent coating films with smooth surface and
      uniform thickness could be obtained. The contact angles of the coating films for
      water and methylene iodide are extremely high, at 118 degrees and 97 degrees,
      respectively, and their surface free energies are about 9.7 dyn/cm. It was found
      that the water-repellent glass prepared is very hydrophobic and exhibits
      excellent water-repellency. Hydrophobic perfluoroalkyl groups are preferentially
      enriched to the outermost layer at the coating film-air interface, and two layers
      probably exist in the coating film. The upper layer oriented toward the air is
      composed of mainly perfluoroalkyl groups originating from PFAS, and the lower
      layer is composed of mainly -OSiO- groups originating from TEOS. The heat
      treatment after drying step cannot influence the surface enrichment of the
      perfluoroalkyl group. The hydrolysis reaction should be more completely done
      before the dip coating step to obtain lower surface free energy. The burning
      temperature should be less than 300 degrees C because the perfluoroalkyl group
      begins to decompose from this temperature. Copyright 2001 Academic Press. 

PMID- 11237452
TI  - Adsorption Behavior of N(2), Water, C(6) Hydrocarbons, and Bulkier Benzene
      Derivative (TMB) on Na-X Zeolite and Its K(+)-, Rb(+)-, and Cs(+)-Exchanged
      Analogues.
AB  - The hydrothermal crystallization of X-type zeolite with a Si/Al ratio of 1.15 was
      achieved from the Na(2)O-Al(2)O(3)-SiO(2)-H(2)O system at 368 K under static
      conditions. The post-synthesis modification was carried out by a conventional ion
      exchange technique to obtain K(+)-, Rb(+)-, and Cs(+)-exchanged samples with
      different degrees of exchange. All the samples were characterized using chemical
      analysis, IR, SEM, powder XRD, low-temperature nitrogen adsorption, and
      equilibrium sorption uptakes of different probe molecules. The relative
      intensities of the XRD peaks of cation-exchanged zeolite were found to be
      affected to different extents, depending on the nature and the concentration of
      nonframework cationic size, without any shift in the positions of reflection. The
      sorptive properties of the K-, Rb-, and Cs-exchanged samples were studied using
      nitrogen, water, and different C(6) hydrocarbons including bulkier benzene
      derivative 1,3,5-trimethylbenzene (TMB) as probe molecules. The trend observed in
      chemical potential estimated as a function of nitrogen coverage indicates
      different sorption selectivity because of differences in the cationic size and
      population. Sorption uptake kinetics for probe molecules such as water, n-hexane,
      cyclohexane, benzene, and TMB were also studied. The samples with higher degrees
      of exchange and/or cationic size have shown a decrease in hydrophilic character
      due to the formation of irregular networks of water molecules connected with
      preadsorbed water molecules, framework oxygen ions, and nonframework cations.
      Among C(6) hydrocarbons including TMB, the benzene molecule is found to be the
      most promising probe for the estimation of openness of structure and surface
      heterogeneity as well. Copyright 2001 Academic Press. 

PMID- 11237453
TI  - On the Viscosity of Dilute Emulsions.
AB  - The slow motion of a liquid droplet in a shear flow in the presence of
      surfactants is studied. The effects of the interfacial viscosity, Gibbs
      elasticity, surface diffusion and bulk diffusion of surfactants in both phases
      are taken into account. The analytical solution of the problem for small Reynolds
      and Peclet numbers gives a simple criterion for estimation of the tangential
      mobility of the droplet interface. By applying the standard procedure for
      averaging of the stress tensor flux at an arbitrary surface of the dilute
      emulsion, an analytical formula for the viscosity of emulsions in the presence of
      surfactants is derived. The result is a natural generalization of the well-known
      formula of Einstein for the viscosity of monodisperse dilute suspensions and of
      the expressions derived by Taylor and Oldroyd for the viscosity of monodisperse
      dilute emulsions taking into account the Marangoni effect. Copyright 2001
      Academic Press. 

PMID- 11237454
TI  - The Significance of Interfacial Water Structure in Soluble Salt Flotation
      Systems.
AB  - Flotation of soluble salts with dodecyl amine hydrochloride (DAH) and sodium
      dodecyl sulfate (SDS) collectors has demonstrated that the interfacial water
      structure and hydration states of soluble salt surfaces together with the
      precipitation tendency of the corresponding collector salts are of considerable
      importance in explaining their flotation behavior. In particular, the high
      concentration of ions in these soluble salt brines and their hydration appear to
      modify the bulk and interfacial structure of water as revealed by contact angle
      measurements and this effect is shown to be an important feature in the flotation
      chemistry of soluble salt minerals including alkali halide and alkali oxyanion
      salts. Depending on characteristic chemical features (salt type), the salt can
      serve either as a structure maker, in which intermolecular hydrogen bonding
      between water molecules is facilitated, or as a structure breaker, in which
      intermolecular hydrogen bonding between water molecules is disrupted. For
      structure making salts the brine completely wets the salt surface and no contact
      angle can be measured. For structure breaking salts the brine does not completely
      wet the salt surface and a finite contact angle is measured. In this regard it
      has been found that soluble salt flotation either with the cationic DAH or
      anionic SDS collector is possible only if the salt is a structure breaker.
      Copyright 2001 Academic Press. 

PMID- 11237455
TI  - Quantitative Analysis of Fluid Interface-Atomic Force Microscopy.
AB  - Net repulsive interactions between n-hexadecane and a poly-styrene microsphere in
      aqueous solutions are measured with atomic force microscopy and interpreted using
      the augmented Young-Laplace equation. The true separation between probe and fluid
      interface is implicitly computed from the force-distance data, providing a more
      accurate description of drop or bubble deformation. Experiments and theoretical
      arguments demonstrate that a fluid interface stiffens with increasing deformation
      and is not accurately treated as a Hookean spring. The unexpected stability of
      the draining aqueous film between hydrophobic bodies in electrolyte solutions is
      explained primarily by the deformation of the oil drop in response to the applied
      normal force, as well as the increased hydrodynamic resistance due to the
      increased drainage area. Copyright 2001 Academic Press. 

PMID- 11237456
TI  - Mechanical Stability Criterion, Triple-Phase Condition, and Pressure Differences
      of Matter Condensed in a Porous Matrix.
AB  - In contrast to the triple-point condition of bulk material, condensed matter in
      porous media can coexist stably as liquid, solid, and vapor over a wide
      temperature range. The necessary conditions are found by a thermodynamic approach
      starting with the potential which reflects the grand canonical distribution and
      is characterized by heat and matter exchange. The other parameters are volume and
      surface. Therefore, it is designated the free mechanical potential. General
      expressions for mechanical stability are given. On condensation and melting the
      nonwetting phases vanish. These are thermodynamically stable phase transitions.
      For the opposing effects evaporation and fusion, an energy barrier must be
      transgressed either by nucleation or by intrusion as discussed here. These are
      metastable states. Phase transitions are the conditions which limit the triple
      phase region. Within this region high negative pressures are generated in the
      unfrozen liquid independent of the pore size where it exists. The findings are
      applied to water in the disperse matrix of hardened cement paste. They are the
      basis for "micro ice lens pumping". Copyright 2001 Academic Press. 

PMID- 11237457
TI  - Binding of Biotin to Gold Surfaces Functionalized by Self-Assembled Monolayers of
      Cystamine and Cysteamine: Combined FT-IRRAS and XPS Characterization.
AB  - As part of our project of developing a new IR-based immunosensor, we investigated
      the functionalization of gold substrates with thin organic films containing
      biotin ligands. A two-step procedure was developed consisting of the
      chemisorption of short amine-terminated organosulfur compounds, followed by their
      reaction at the solid liquid interface with an activated ester derivative of
      biotin. Covalent binding of biotin to these attachment layers was assessed by
      Fourier transform infrared reflection-absorption spectroscopy (FT-IRRAS) and X
      ray photoelectron spectroscopy (XPS). The interaction of activated biotin with
      alcohol- and carboxylic acid-terminated monolayers was also investigated, and, as
      expected, no binding occurred. Moreover, mixed layers of short alcohol- and amine
      terminated thiolates were successfully constructed at the gold surfaces and were
      shown to be the most efficient for the covalent binding of biotin thanks to the
      blocking effect of the thioalcohol, which prevented direct adsorption of biotin
      to the gold surface. Copyright 2001 Academic Press. 

PMID- 11237458
TI  - Static Method to Evaluate Interaction Forces by AFM.
AB  - An atomic force microscope (AFM) is a very powerful tool to evaluate interaction
      forces between surfaces in liquids on the molecular scale, but the apparatus was
      not designed to measure forces in equilibrium. Hence, data obtained by AFM are
      not in equilibrium in principle. Here we propose a static method to obtain
      interaction forces between stationary surfaces in aqueous solutions using AFM.
      The validity of the proposed method was confirmed by comparing interaction forces
      measured by this method with those by the normal dynamic method for the system of
      a mica plate and a silica particle in electrolyte solutions where an equilibrium
      was nearly achieved because water molecules and ions moved much faster than
      surfaces. The applicability of this method to the measurement of hydrophobic
      attraction was then examined, and important information on the attraction was
      obtained. Copyright 2001 Academic Press. 

PMID- 11237459
TI  - Frothing Behavior of Nonionic Surfactant Solutions in the Presence of Organic and
      Inorganic Electrolytes.
AB  - The influence of inorganic salts (KCl, KBr, NaI, KI) and organic salts,
      tetrapentyl ammonium bromide (TPeAB) and tetrabutyl ammonium bromide (TBuAB), on
      the decay of a foam column from aqueous solutions of octaethyleneglycol mono-n
      decylether (C(10)E(8)) has been investigated. The salt concentration in all cases
      was maintained constant (0.01 M). The results from the measurements of the foam
      decay rates indicate that, of the inorganic electrolytes, KBr is a foam
      destabilizer, KCl does not influence the froth stability, and NaI and KI act as
      foam stabilizers. Both TBuAB and TPeAB generate greater initial quantities of
      foam. Concurrently, both organic salts accelerate the destruction of the foam in
      the initial stage of drainage, the effect of TBuAB being stronger. It was
      established also that in the later stage of drainage, where black films form
      (here C(10)E(8) bulk concentration is 5 x 10(-4) M and its C(bl)=10(-4) M), TPeAB
      acts as foam destabilizer, while TBuAB does not influence the foam stability.
      Copyright 2001 Academic Press. 

PMID- 11237460
TI  - On the Spreading of Glycerol Trioleate.
AB  - Spreading of liquids can often successfully be described by either hydrodynamic
      or molecular kinetics theories. The natural wetting of small, sessile drops of
      glycerol trioleate on smooth, flat, solid surfaces may be expected to comply with
      the former model, yet nonnegligible differences are manifest, which apparently
      cannot be accounted for by the addition of a molecular kinetics term. We
      postulate that modifications to the spreading rate are due to an effect of time
      dependent molecular orientation occurring after liquid molecules have contacted
      the solid substrate. Copyright 2001 Academic Press. 

PMID- 11237461
TI  - Comparative aspects of animal oogenesis.

PMID- 11237462
TI  - Dermal fibroblast-derived growth factors restore the ability of beta(1) integrin
      deficient embryonal stem cells to differentiate into keratinocytes.
AB  - Embryonal stem (ES) cells that are homozygous null for the beta(1) integrin
      subunit fail to differentiate into keratinocytes in vitro but do differentiate in
      teratomas and wild-type/beta(1)-null chimeric mice. The failure of beta(1)-null
      ES cells to differentiate in culture might be the result of defective
      extracellular matrix assembly or reduced sensitivity to soluble inducing factors.
      By culturing embryoid bodies on dead, deepidermized human dermis (DED) we showed
      that epidermal basement membrane did not induce beta(1)-null ES cells to undergo
      keratinocyte differentiation and did not stimulate the differentiation of wild
      type ES cells. Coculture with epidermal keratinocytes also had no effect.
      However, when human dermal fibroblasts were incorporated into DED, the number of
      epidermal cysts formed by wild-type ES cells increased dramatically, and small
      groups of keratin 14-positive cells differentiated from beta(1)-null ES cells.
      Fibroblast-conditioned medium stimulated differentiation of K14-positive cells in
      wild-type and beta(1)-null embryoid bodies. Of a range of growth factors tested,
      KGF, FGF10, and TGFalpha all stimulated differentiation of keratin 14-positive
      beta(1)-null cells, and KGF and FGF10 were shown to be produced by the
      fibroblasts used in coculture experiments. The effects of the growth factors on
      wild-type ES cells were much less pronounced, suggesting that the concentrations
      of inducing factors already present in the medium were not limiting for wild-type
      cells. We conclude that the lack of beta(1) integrins decreases the sensitivity
      of ES cells to soluble factors that induce keratinocyte differentiation.

PMID- 11237463
TI  - Connexin31-deficiency in mice causes transient placental dysmorphogenesis but
      does not impair hearing and skin differentiation.
AB  - Mutations in the human GJB3 gene that codes for Connexin31 (Cx31), a protein
      subunit of gap junction channels, have recently been reported to cause deafness
      and the skin disorder erythrokeratodermia variabilis. To study the function of
      this gene in mice, we generated animals with targeted replacement of the Cx31
      gene (Gjb3) by a lacZ reporter gene. Although homozygous Cx31-deficient adult
      mice (Gjb3(-/-)) were found among the offspring of heterozygous Cx31-deficient
      parents (Gjb3(+/-)), 60% of the animals expected according to Mendelian
      inheritance were lost between ED 10.5 and 13.5. Placentas of Gjb3(-/-) embryos at
      ED 9.5 were smaller than controls as a result of severely reduced labyrinth and
      spongiotrophoblast size. From ED 10.5 onward, placentas of surviving Gjb3(-/-)
      embryos recovered progressively and reached normal size and morphology by ED
      18.5. This corresponds to a time period in which another connexin isoform,
      Connexin43, is upregulated in spongiotrophoblast cells of Cx31-deficient and
      control placentas. No morphological or functional defects of skin or inner ear
      were observed in surviving adult Gjb3(-/-) mice. We conclude that Cx31 is
      essential for early placentation but can be compensated for by other connexins in
      the embryo proper and adult mouse.

PMID- 11237464
TI  - Nerve-muscle interactions regulate motor terminal growth and myoblast
      distribution during muscle development.
AB  - Interactions between motoneurons and muscles influence many aspects of
      neuromuscular development in all animals. These interactions can be readily
      investigated during adult muscle development in holometabolous insects. In this
      study, the development of the dorsolongitudinal flight muscle (DLM) and its
      innervation is investigated in the moth, Manduca sexta, to address the
      specificity of neuromuscular interactions. The DLM develops from an anlage
      containing both regressed larval template fibers and imaginal myoblasts. In the
      adult, each fiber bundle (DLM1-5) is innervated by a single motoneuron (MN1-MN5),
      with the dorsal-most fiber bundle (DLM5) innervated by a mesothoracic motoneuron
      (MN5). The DLM failed to develop following complete denervation because myoblasts
      failed to accumulate in the DLM anlage. After lesioning MN1-4, MN5 retained its
      specificity for the DLM5 region of the anlage and failed to rescue DLM1-4. Thus
      specific innervation of the DLM fiber bundles does not depend on interactions
      among motoneurons. Myoblast accumulation, but not myonuclear proliferation,
      increased around the MN5 terminals, producing a hypertrophied adult DLM5.
      Therefore, motoneurons compete for uncommitted myoblasts. MN5 terminals
      subsequently grew more rapidly over the hypertrophied DLM5 anlage, indicating
      that motoneuron terminal expansion is regulated by the size of the target muscle
      anlage.

PMID- 11237465
TI  - The LAX1 and FRIZZY PANICLE 2 genes determine the inflorescence architecture of
      rice by controlling rachis-branch and spikelet development.
AB  - We have analyzed two mutants that exhibit altered panicle architecture in rice
      (Oryza sativa L.). In lax1-2, which is a new and stronger allele of the
      previously reported lax mutant, initiation and/or maintenance of rachis-branches,
      lateral spikelets, and terminal spikelets was severely prevented. In situ
      hybridization analysis using OSH1, a rice knotted1 (kn1) ortholog, confirmed the
      absence of lateral meristems in lax1-2 panicles. These defects indicate that the
      LAX1 gene is required for the initiation/maintenance of axillary meristems in the
      rice panicle. In addition to its role in forming lateral meristems, the wild-type
      LAX1 gene acts as a floral meristem identity gene which specifies the terminal
      spikelet meristem. A comparison of the defects in lax1-1 and lax1-2 plants
      suggested that the sensitivities to reduced LAX1 activity were not uniform among
      different types of meristems. In the fzp2 mutant panicle, the basic branching
      pattern of the panicle was indistinguishable from that of the wild type; however,
      specification of both terminal and lateral spikelet meristems was blocked, and
      sequential rounds of branching occurred at the point where the spikelet meristems
      are initiated in the wild-type panicle. This resulted in the generation of a
      panicle composed of excessive ramification of rachis-branches. The lax1-1 fzp2
      double mutants exhibited a novel, basically additive, phenotype, which suggests
      that LAX1 and FZP2 function in genetically independent pathways.

PMID- 11237466
TI  - Loss-of-function mutations reveal that the Drosophila nautilus gene is not
      essential for embryonic myogenesis or viability.
AB  - nautilus (nau), the single Drosophila member of the bHLH-containing myogenic
      regulatory family of genes, is expressed in a subset of muscle precursors and
      differentiated fibers. It is capable of inducing muscle-specific transcription as
      well as myogenic transformation, and plays a role in the differentiation of a
      subset of muscle precursors into mature muscle fibers. In previous studies, the
      nau zygotic loss-of-function phenotype was determined using genetic deficiencies
      in which the gene is deleted. We note that this genetic loss-of-function
      phenotype differs from the loss-of-function phenotype determined using RNA
      interference (L. Misquitta and B. M. Paterson, 1999, Proc. Natl. Acad. Sci. USA
      96, 1451-1456). The present study re-examines this loss-of-function phenotype
      using EMS-induced mutations that specifically alter the nau gene, and extends the
      genetic analysis to include the loss of both maternal and zygotic nau function.
      In brief, embryos lacking nau both maternally and zygotically are missing a
      distinct subset of muscle fibers, consistent with its apparent expression in a
      subset of muscle fibers. The muscle loss is tolerated, however, such that the
      loss of nau both maternally and zygotically does not result in lethality at any
      stage of development.

PMID- 11237467
TI  - Paternal chromosome incorporation into the zygote nucleus is controlled by
      maternal haploid in Drosophila.
AB  - maternal haploid (mh) is a strict maternal effect mutation that causes the
      production of haploid gynogenetic embryos (eggs are fertilized but only maternal
      chromosomes participate in development). We conducted a cytological analysis of
      fertilization and early development in mh eggs to elucidate the mechanism of
      paternal chromosome elimination. In mh eggs, as in wild-type eggs, male and
      female pronuclei migrate and appose, the first mitotic spindle forms, and both
      parental sets of chromosomes congress on the metaphase plate. In contrast to
      control eggs, mh paternal sister chromatids fail to separate in anaphase of the
      first division. As a consequence the paternal chromatin stretches and forms a
      bridge in telophase. During the first three embryonic divisions, damaged paternal
      chromosomes are progressively eliminated from the spindles that organize around
      maternal chromosomes. A majority of mh embryos do not survive the deleterious
      presence of aneuploid nuclei and rapidly arrest their development. The rest of mh
      embryos develop as haploid gynogenetic embryos and die before hatching. The mh
      phenotype is highly reminiscent of the early developmental defects observed in
      eggs fertilized by ms(3)K81 mutant males and in eggs produced in incompatible
      crosses of Drosophila harboring the endosymbiont bacteria Wolbachia.

PMID- 11237469
TI  - Formation of the middle ear: recent progress on the developmental and molecular
      mechanisms.
AB  - The middle ear allows animals to hear while moving in an aerial medium. It is
      composed of a cavity harbouring a chain of three ossicles that transmit
      vibrations produced by airborne sound in the tympanic membrane into the inner
      ear, where they are converted into neural impulses. The middle ear develops in
      the branchial arches, and this requires sequential interactions between the
      epithelia and the underlying mesenchyme. Gene-inactivation experiments have
      identified genes required for the formation of different middle ear components.
      Some encode for signalling molecules, including Endothelin1 and Fgf8, probable
      mediators of epithelial-mesenchymal interactions. Other genes, including Eya1,
      Prx1, Hoxa1, Hoxa2, Dlx1, Dlx2, Dlx5, and Gsc, are most likely involved in
      patterning and morphogenetic processes in the neural crest-derived mesenchyme.
      Mechanisms controlling formation of a functional tympanic membrane are also
      discussed. Basically, the tympanic ring, which serves as support for the tympanic
      membrane, directs invagination of the first pharyngeal cleft ectoderm to form the
      external acoustic meatus (EAM), which provides the outer layer of the membrane.
      Gsc and Prx1 are essential for tympanic ring development. While invaginating, the
      EAM controls skeletogenesis in the underlying mesenchyme to form the manubrium of
      the malleus, the link between the membrane and the middle ear ossicles.

PMID- 11237468
TI  - Regulation of dharma/bozozok by the Wnt pathway.
AB  - The zebrafish homeobox gene dharma/bozozok (boz) is required for the formation
      and/or function of the Nieuwkoop center and the subsequent induction of the
      Spemann organizer. dharma is expressed soon after the midblastula transition in
      the dorsal blastomeres and the dorsal yolk syncytial layer (YSL). We found that
      the expression of dharma was upregulated or ectopically induced by misexpression
      of a Wnt protein and cytoplasmic components of the Wnt signaling pathway and
      downregulated by the expression of dominant-negative Tcf3. A 1.4-kbp fragment of
      the dharma promoter region contains consensus sequences for Tcf/Lef binding
      sites. This promoter region recapitulated the Wnt-dependent and dorsal dharma
      expression pattern when it was fused to luciferase or GFP. Deletion and point
      mutant analyses revealed that the Tcf/Lef binding sites were required to drive
      this expression pattern. These data established that dharma/boz functions between
      the dorsal determinants-mediated Wnt signals and the formation of the Nieuwkoop
      center.

PMID- 11237471
TI  - Nerve-independence of limb regeneration in larval Xenopus laevis is correlated to
      the level of fgf-2 mRNA expression in limb tissues.
AB  - In both larval and adult urodele amphibians, limb blastema formation requires the
      presence of an adequate nerve supply. In previous research, we demonstrated that
      the hindlimb of early Xenopus laevis larvae formed a regeneration blastema even
      when denervated, while the denervated limb of late larvae did not. We
      hypothesized that the nerve-independence was due to the autonomous synthesis of a
      mitogenic neurotrophic-like factor by undifferentiated limb bud cells. In this
      paper, we demonstrate that fgf-2 mRNA is present in larval limb tissues and that
      its level is correlated to the extent of mesenchymal cells populating the limb:
      in early limbs, fgf-2 mRNA is present at high levels all over the limb, while, in
      late limbs, the fgf-2 expression is low and detectable only in the distal
      autopodium. After denervation, fgf-2 mRNA synthesis increases in amputated early
      limbs but not in amputated late limbs. The implantation of anti-FGF-2 beads into
      amputated early limbs hardly lowers the mitotic activity of blastema cells.
      However, FGF-2 beads implanted into the blastema of late limbs prevent the
      denervation-induced inhibition of mitosis and oppose blastema regression. Our
      data indicate that FGF-2 is a good candidate for the endogenous mitogenic factor
      responsible for blastema formation and growth in amputated and denervated early
      limbs. However, in amputated late limbs, the very limited fgf-2 expression is not
      sufficient to promote blastema formation in the absence of nerves.

PMID- 11237470
TI  - Functional analysis of zebrafish GDNF.
AB  - We have identified zebrafish orthologues of glial cell line-derived neurotrophic
      factor (GDNF) and the ligand-binding component of its receptor GFRalpha1. We
      examined the mRNA expression pattern of these genes in the developing spinal cord
      primary motor neurons (PMN), kidney, and enteric nervous systems (ENS) and have
      identified areas of correlated expression of the ligand and the receptor that
      suggest functional significance. Many aspects of zebrafish GDNF expression appear
      conserved with those reported in mouse, rat, and avian systems. In the zebrafish
      PMN, GFRalpha1 is only expressed in the CaP motor neuron while GDNF is expressed
      in the ventral somitic muscle that it innervates. To test the functional
      significance of this correlated expression pattern, we ectopically overexpressed
      GDNF in somitic muscle during the period of motor axon outgrowth and found
      specific perturbations in the pattern of CaP axon growth. We also depleted GDNF
      protein in zebrafish embryos using morpholino antisense oligos and found that
      GDNF protein is critical for the development of the zebrafish ENS but appears
      dispensable for the development of the kidney and PMN.

PMID- 11237472
TI  - CPEB degradation during Xenopus oocyte maturation requires a PEST domain and the
      26S proteasome.
AB  - Cytoplasmic poly(A) elongation is widely utilized during the early development of
      many organisms as a mechanism for translational activation. Targeting of mRNAs
      for this mechanism requires the presence of a U-rich element, the cytoplasmic
      polyadenylation element (CPE), and its binding protein, CPEB. Blocking
      cytoplasmic polyadenylation by interfering with the CPE or CPEB prevents the
      translational activation of mRNAs that are crucial for oocyte maturation. The CPE
      sequence and CPEB are also important for translational repression of mRNAs stored
      in the Xenopus oocyte during oogenesis. To understand the contribution of protein
      metabolism to these two roles for CPEB, we have examined the mechanisms
      influencing the expression of CPEB during oogenesis and oocyte maturation.
      Through a comparison of CPEB mRNA levels, protein synthesis, and accumulation, we
      find that CPEB is synthesized during oogenesis and stockpiled in the oocyte.
      Minimal synthesis of CPEB, <3.6%, occurs during oocyte maturation. In late oocyte
      maturation, 75% of CPEB is degraded coincident with germinal vesicle breakdown.
      Using proteasome and ubiquitination inhibitors, we demonstrate that CPEB
      degradation occurs via the proteasome pathway, most likely through ubiquitin
      conjugated intermediates. In addition, we demonstrate that degradation requires a
      14 amino acid PEST domain.

PMID- 11237473
TI  - Comparative studies on lipid peroxidation of microsomes and mitochondria obtained
      from different rat tissues: effect of retinyl palmitate.
AB  - The effect of retinyl palmitate on the polyunsaturated fatty-acid composition,
      chemiluminescence and peroxidizability index of microsomes and mitochondria
      obtained from rat liver, kidney, brain, lung and heart, was studied. After
      incubation of microsomes and mitochondria in an ascorbate Fe++ system (120 min at
      37 degrees C) it was observed that the total cpm/mg protein originated from light
      emission: chemiluminescence was lower in liver microsomes, mitochondria and
      kidney microsomes in the vitamin A group than in the control group. In
      mitochondria obtained from control rats, the most sensitive fatty acids for
      peroxidation were arachidonic acid C20:4 n6 in liver and docosahexaenoic acid
      C22:6 n3 in kidney and brain. In microsomes obtained from control rats, the most
      sensitive fatty acids for peroxidation were linoleic acid C18:2 n6 and C20:4 n6
      in liver and C22:6 n3 in kidney. Changes in the most polyunsaturated fatty acids
      were not observed in organelles obtained from lung and heart. As a consequence
      the peroxidizability index, a parameter based on the maximal rate of oxidation of
      fatty acids, showed significant changes in liver, kidney and brain mitochondria,
      while in microsomes changes were significant in liver and kidney. These changes
      were less pronounced in membranes derived from rats receiving vitamin A. Our
      results confirm and extend previous observations that indicated that vitamin A
      may act as an antioxidant protecting membranes from deleterious effects.

PMID- 11237474
TI  - A novel derivative pentacyclic triterpene and omega 3 fatty acid.
AB  - Adjuvant induced arthritis (AIA) is accompanied by marked changes in the levels
      of lysosomal enzymes, glycoproteins and metabolic turnover of collagen. The role
      of a pentacyclic triterpene and eicosapentaenoic acid (EPA) derivative--Lupeol
      EPA (50 mg/kg body weight--orally) was tested in vivo in rats. The increased
      activities of lysosomal enzymes and glycoproteins associated with decreased
      collagen in arthritic animals were significantly altered to nearly that of
      controls. Indomethacin (3 mg/kg body weight) was used as a reference compound.
      The therapeutic usefulness of Lupeol-EPA derivative in inflammatory conditions is
      attractive and deserves further work in this direction.

PMID- 11237475
TI  - Indomethacin increases 15-PGDH mRNA expression in HL60 cells differentiated by
      PMA.
AB  - We previously reported an induction of 15-hydroxyprostaglandin dehydrogenase type
      I mRNA (15-PGDH) expression accompanied by a decrease in prostaglandin E2(PGE2)
      levels during cord blood monocytes differentiation into preosteoclastic cells by
      1,25 dihydroxyvitamin D3 (1,25 (OH)2D3). These results suggested a role of
      prostaglandin (PG) enzymes in adhesion and/or differentiation of monocytes. In
      the present work, we studied modulation of gene expression of PG metabolism
      enzymes mRNAs in HL60 cells differentiated by phorbol myristate acetate (PMA)
      into the monocyte/macrophage lineage. We showed that adhesion of HL60 induced by
      PMA causes an increase of cyclooxygenase 2 (COX 2) and 15-PGDH mRNAs. When adding
      indomethacin, a non steroidal antiinflammatory drug known to inhibit COX
      activity, the cells remained attached and expressed large amounts of 15-PGDH mRNA
      while COX 2 mRNA expression remained unchanged. Indomethacin, in association with
      PMA can consequently exert a dual control on key enzymes of PGE2 metabolism
      without modifying adhesion of the cells.

PMID- 11237476
TI  - Volume-induced natriuresis in healthy women: renal metabolism of prostacyclin and
      thromboxane, and physiological role of prostanoids.
AB  - In healthy women submitted to a short-term expansion in extracellular fluid
      volume we have evaluated the urinary excretory profile of the stable metabolites
      of prostaglandin(PG) I2 and thromboxane(TX) A2, 6-keto-PGF1 alpha(6KPGF) and TXB2
      respectively, and assessed the physiological role played by the prostanoids in
      this experimental condition. Salt retention (SR group, n=9) was induced by
      repeated i.v. infusion of saline solution (0.9% NaCl). At the end of the
      treatment the body weight had increased by 0.7+/-0.2 kg (mean+/-SEM) (P<0.05).
      Renal functional exploration [clearance (cl.) method] was performed during
      hypotonic polyuria (induced by oral water load) and subsequent moderate
      antidiuresis (induced by low-dose infusion of an antidiuretic hormone analogue).
      Urinary 6KPGF and TXB2 concentrations were estimated by RIA method during
      polyuria (P cl. period), early and late antidiuresis (A1 and A2 cl. periods).
      Paired functional explorations were performed in absence (control study) and
      presence of indomethacin. Basal values of plasma sodium and potassium
      concentrations, plasma renin activity (PRA) and urinary aldosterone excretion
      were determined just before the control study. The results in salt retention were
      compared to those previously obtained in healthy women submitted to a moderate
      salt depletion (SD2 group, n=6), in absence and presence of the drug. Women in
      salt retention received 100 mg i.m. of the drug, whereas salt-depleted women
      received only a halved dose as in previous studies in salt depletion the full
      dose produced prolonged anuria. (I) Salt retention vs salt depletion. The basal
      values of PRA and urinary aldosterone excretion were significantly lower. During
      polyuria, urinary excretion of 6KPGF, 6KPGF/TXB2 ratio, urinary flow rate,
      creatinine cl. and absolute and fractional excretions of sodium and chloride were
      significantly higher. In salt retention during polyuria, significant positive
      correlations were found between 6KPGF excretion and functional excretory
      parameters. (II) Indomethacin in salt retention. The following effects were
      significant: (a) a reduction in prostanoid excretions in P and A1 cl. periods
      only; (b) during polyuria, an increase in arterial pressure, a reduction in
      urinary flow rate and creatinine cl. (saluresis showed not significant
      reduction). During polyuria significant positive correlations occurred between
      the absolute effects of indomethacin on 6KPGF excretion and those on functional
      excretory parameters. (III) Comparative effects of indomethacin in salt retention
      and salt depletion. Despite the double dosage of the drug, the significant
      reductions in urinary metabolite excretions were not significantly different
      during P cl. period and significantly lower in A1 cl. period compared to the
      corresponding significant reductions in salt depletion. During polyuria, the
      significant increase in arterial pressure was significantly different from the
      not significant effect in salt depletion; the not significant effect on saluresis
      was significantly different from the significant reduction in salt depletion. The
      results suggest the following conclusions: (1) The present model showed the
      functional pattern of the volume-natriuresis; (2) In salt retention, in contrast
      with salt depletion, indomethacin induced an increase in arterial pressure
      consistent with the inhibition of a PG-dependent vasodilator mechanism active at
      the systemic level; (3) In salt retention, in contrast with salt depletion,
      indomethacin failed to induce a significant reduction in saluresis. This failure
      can be attributed to the drug's blunted effectiveness in inhibiting the renal
      synthesis of saluretic PGs, and probably to the interference of the concurrent
      increase in arterial pressure in the renal treatment of sodium and chloride.

PMID- 11237477
TI  - Breastfeeding duration, milk fat composition and developmental indices at 1 year
      of life among breastfed infants.
AB  - The associations of breastfeeding duration and milk fat composition with the
      developmental outcome at 1 year of age were measured within 44 infants
      exclusively breastfed for 3 months, out of 95 recruited at birth. Pooled breast
      milk (hindmilk) of the mothers was analysed at colostrum, 1, 3, 6, 9, and 12
      months for total fat and fatty acid content. Infants were examined at 12 months
      by means of the Bayley test. There was a progressive reduction of the number of
      breastfed babies after the introduction of solids to 29 (6 months), 17 (9 months)
      and 10 (12 months). After adjusting for major confounders, infants breastfed for
      6 months or longer showed a trend to have an advantage at the Bayley psychomotor
      developmental index compared to those breastfed >3 and <6 months (95% CI for
      difference: - 0.6, 13.8; P= 0.07) while the Bayley mental developmental index
      (MDI) was just 2.1 points higher. Among the milk fat components considered for
      each time-point, the total fat content at 6 months showed the strongest
      association with the MDI at 12 months (r=0.59, P=0.001). Prolonging breastfeeding
      during the weaning process may result in a better developmental performance at 12
      months, possibly due to the supply of fats affecting brain composition.

PMID- 11237478
TI  - Biochemical effects of supplemented long-chain polyunsaturated fatty acids in
      hyperphenylalaninemia.
AB  - Hyperphenylalaninemic (HPA) children display low levels of long-chain
      polyunsaturated fatty acids (LCPUFA), particularly docosahexaenoic acid (DHA), in
      circulating lipids and erythrocytes. We have investigated the effects on the
      blood fatty acid status and lipid picture of a balanced supplementation with
      LCPUFA in HPA children through a double-blind, placebo-controlled trial. A total
      of 20 well-controlled HPA, school-age children were randomized to receive through
      a 12-month trial fat capsules supplying either 26% fatty acid as LCPUFA
      (including 4.6%gamma -linolenic acid, 7.4% arachidonic acid, AA, 5.5%
      eicosapentaenoic acid and 8% DHA) or placebo (olive oil). The study
      supplementation was administered in order to provide 0.3-0.5% of the individual
      daily energy requirements as LCPUFA. Reference data were obtained from healthy
      children of comparable age. Among HPA children (whose DHA status was poor at
      baseline), those supplemented with LCPUFA showed an increase of around 100% in
      the baseline DHA levels in plasma phospholipids and erythrocytes. No changes of
      AA levels were observed. Blood lipid levels did not significantly change. A
      balanced supplementation with LCPUFA in treated HPA children may improve the DHA
      status without adversely affecting the AA status.

PMID- 11237479
TI  - Mechanisms involved in prostaglandin-induced increase in bone resorption in
      neonatal mouse calvaria.
AB  - Prostaglandins (PG) E1, E2 and F2alpha induce bone resorption in isolated
      neonatal parietal bone cultures, and an associated increase in interleukin-6 (IL
      6) production. Indomethacin had little effect on the response to PGE2, or the
      relatively non-selective EP receptor agonists 11-deoxy PGE1 and misoprostol, but
      blocked the effects of PGF2alpha and the F receptor agonist fluprostenol,
      indicating an indirect action via release of other prostaglandins. It is more
      likely that there is positive autoregulation of prostaglandins production in this
      preparation mediated via stimulation of F receptors. The effects of selective EP
      receptor agonists sulprostone (EP1,3) and 17-phenyl trinor PGE2(EP1), indicated
      the involvement of EP2 and/or EP4 receptors, which signal via cAMP. The
      relatively weak increase in IL-6 production by misoprostol (with respect to
      resorption) suggests that these responses are controlled by different combination
      of EP2 and EP4 receptors. The PKA activator, forskolin, induced small increases
      in bone resorption at lower concentrations (50-500 ng/ml) but a reversal of this
      effect, and inhibition of resorption induced by other stimuli (PTH, PGE2), at
      higher concentrations (0.5-5 microg/ml). IL-6 production was markedly increased
      only at the higher concentrations. The inhibitory effect of forskolin may be a
      calcitonin-mimetic effect. PMA induced both resorption and IL-6 production which
      were both blocked by indomethacin, indicating a role for PKC in the control of
      prostaglandin production.

PMID- 11237480
TI  - Modulation of PGE2 generation in the diabetic embryo: effect of nitric oxide and
      superoxide dismutase.
AB  - In this work we assessed NO levels in the control and diabetic embryo during
      early organogenesis, and the ability of NO and SOD to modify embryonic PGE2
      levels. Rats were made diabetic by steptozotocin (60 mg/kg) before mating.
      Diabetic embryos (day 10 of gestation) show increased nitrate/nitrite levels and
      enhanced NOS activity. The diabetic embryos release to the incubation medium
      increased amounts of PGE2 and have diminished PGE2 content. In the control embryo
      NO modulates PGE2 levels, but this modulatory pathway is not observed in the
      diabetic embryos. The diminished PGE2 content and the enhanced PGE2 release is
      prevented by SOD additions, both in the diabetic embryos and in control embryos
      cultured in the presence of diabetic serum (24 h culture, explantation day 9).
      The present results show that SOD additions prevent the abnormalities in the
      accumulation, production and release of PGE2 in diabetic embryos, probably
      related to the decrease in malformations.

PMID- 11237481
TI  - Gestational age-dependent effects of lipopolysaccharide on prostaglandin
      production by murine decidual caps.
AB  - We sought to determine whether the gestational age of the pregnant mouse had any
      relationship with its lipopolysaccharide (LPS) responsiveness. Murine decidual
      caps from days 13, 15 and 17 of gestation (term is day 20) were dissected out,
      placed in inserts and equilibrated in media overnight. The following day, media
      were removed, replaced with fresh media (+/-LPS at 10 microg/mL). After LPS
      stimulation (24 h), prostaglandin (PG)E2 production by decidual caps from days 13
      and 15 increased by 80-fold and 5-fold, respectively. PGF2alpha, 6-keto-PGF1a and
      TxB2 production also increased. Day 17 decidual caps were unaffected by LPS,
      pregnant mice inoculated i.p. with LPS (50 microg) at day 13 of gestation induced
      100% delivery within 24 h. However, mice treated at days 15 and 17 had an equal
      occurrence of premature delivery or fetal resorption. This change in LPS
      responsiveness may indicate changes in the fetal-maternal immune system in late
      pregnancy.

PMID- 11237484
TI  - Sentinel node biopsy in breast cancer.

PMID- 11237485
TI  - Lessons from Japan--endoscopic management of early gastric and oesophageal
      cancer.
AB  - A significant proportion of gastric and oesophageal cancers are diagnosed at an
      early stage in Japan. Early cancer is not obvious to the untrained eye as the
      mucosal changes are subtle. Better awareness by endoscopists of the different
      appearances of early cancer probably contributes significantly to this high
      incidence in Japan. Routine use of chromoendoscopy in high risk patients is also
      helpful. Survival figures after open surgery for these early cancers are
      excellent. Although the mortality of open surgery for carcinoma of the stomach
      and oesophagus is low, the morbidity is still considerable. A stage of early
      cancer, when the lesion is limited to the mucosa has been demonstrated to have
      minimal risk of metastatic spread (even to the local lymph nodes). These lesions
      can be reliably diagnosed with the help of endoscopic ultrasound. Once diagnosed,
      endoscopic mucosal resection can be performed with low morbidity. This provides
      tissue for histological evaluation, which is a definite advantage over other
      ablative methods used to treat early gastric and oesophageal cancer. Gastric
      cancers which are difficult to resect endoscopically, can be dealt with
      laparoscopically with equally satisfactory results

PMID- 11237486
TI  - Detection of breast cancer after biopsy for false-positive screening mammography.
      An increased risk?
AB  - INTRODUCTION: After false-positive screening for breast cancer, women are still
      at risk of developing breast cancer. In this study the incidence of breast cancer
      in a group of women who had a false-positive outcome is compared with the
      expected breast cancer incidence. METHODS: Follow-up data of 188 women (mean age
      58 years) with a false-positive screening result were collected and analysed for
      breast cancer development. The mean length of follow-up in the study was 7.4
      years. The occurrence of breast cancer was compared to the expected incidence of
      breast cancer in an age-matched control population using figures from the local
      cancer registration. RESULTS: The occurrence of breast cancer in the study
      population (n=7) was not significantly different from the expected incidence of
      breast cancer in the age-matched control group (n=5). CONCLUSION: There is no
      relationship between false-positive findings during breast cancer screening and
      later development of breast cancer. Patients who do not have an increased risk of
      developing breast cancer (due to family history) should not be followed-up
      clinically, but should be returned to the screening programme.

PMID- 11237488
TI  - A comparison of 5-day and 8-day drainage following mastectomy and axillary
      clearance.
AB  - AIMS: Mastectomy and axillary clearance are standard operations for the treatment
      of breast carcinoma. Drainage of the mastectomy site and axilla is often required
      to allow accumulating blood and inflammatory fluids to escape. However, there is
      a lack of data relating to how long suction drains should stay in situ after
      major breast surgery. In our study we have tried to address this deficit by
      comparing the efficacy of 5-day post-operative drainage with 8-day post-operative
      drainage. METHODS: Patients requiring mastectomy and axillary clearance were
      randomized to having drains removed on day 5 or day 8 post-operatively. The
      number of lymphoceles, aspirations and total aspiration volumes in chest and
      axillary drains were compared. RESULTS: From a total of 121 patients enrolled
      into the study, 64 patients were randomized to the 5-day group and 57 to the 8
      day group. There were significant differences regarding the number of aspirations
      and total aspiration volumes in chest and axillary drains between the two groups,
      favouring 8-day drainage. However the number of lymphoceles drained in the 5-day
      group was significantly higher than the 8-day group. CONCLUSIONS: Five-day post
      operative drainage is as safe as 8-day post-operative drainage in the management
      of patients undergoing major breast surgery, but results in an increase in
      lymphocele aspiration and aspiration volume.

PMID- 11237487
TI  - Does intraductal breast cancer spread in a segmental distribution? An analysis of
      residual tumour burden following segmental mastectomy using tumour bed biopsies.
AB  - INTRODUCTION: Breast-conserving surgery for early breast cancer is now routinely
      used as an alternative to mastectomy. Despite post-operative radiotherapy, early
      local recurrence of tumour remains a concern. It has been reported that invasive
      and in-situ ductal carcinoma spread locally through the ductal tree in a
      segmental distribution, however, there is no consensus as to the best surgical
      method to maximize tumour clearance whilst leaving a good cosmetic result. AIM:
      We aimed to measure the effectiveness of segmental mastectomy (excision of tumour
      plus associated segmental ductal tissue) in the clearance of different tumour
      types. Bed biopsy of the excision cavity was employed to assess the rate of
      incomplete excision or the multifocality of certain breast cancers. METHODS: One
      hundred and one patients with breast cancers underwent segmental mastectomy and
      cavity bed biopsies. Specimens were assessed for tumour type and completeness of
      excision. An excision of the cancer was considered incomplete if the margins were
      involved or if any of the bed biopsies showed residual or multifocal tumour.
      RESULTS: A total of 24 patients had incomplete tumour excision. Invasive ductal
      carcinoma was more likely to be completely excised by segmental mastectomy than
      invasive lobular carcinoma (P<0.05). Incomplete excision was associated with
      multifocality and the presence of extensive DCIS. The report of clear
      pathological margins was significantly more likely to be accurate, as measured by
      negative bed biopsies, in invasive ductal carcinoma when compared to invasive
      lobular carcinoma (P<0.05). CONCLUSION: These results support the concept that
      ductal carcinomas spread locally in a segmental fashion. Patients with invasive
      ductal carcinomas are more likely to benefit from breast conserving surgery that
      is tailored to include the associated ductal tissue, in a segmental fashioned
      excision.

PMID- 11237489
TI  - Expression patterns of beta-catenin in in situ and invasive breast cancer.
AB  - BACKGROUND: beta-Catenin plays a central role in the E-cadherin/catenin cell-cell
      adhesion complex and is possibly involved in cellular signalling pathways. In
      this study, we evaluated the expression patterns of this molecule in in situ and
      invasive breast cancer. METHODS: The expression of beta-catenin was evaluated in
      121 breast cancer specimens by immunohistochemistry. Its relationship to
      clinicopathological features was also investigated. RESULTS: Altered beta-catenin
      expression was found in 68% of tumours. Lobular carcinomas showed abnormal beta
      catenin expression more frequently (77%) than ductal carcinomas (64%) with 46% of
      lobular cases showing complete absence of beta-catenin immunoreactivity.
      Cytoplasmic beta-catenin localization was seen only in ductal carcinomas.
      Aberrant beta-catenin expression was observed in 54% of ductal carcinomas in situ
      with highly concordant beta-catenin expression patterns in the nearby in situ and
      invasive components. CONCLUSIONS: Quantitative and qualitative changes in beta
      catenin expression occur in a considerable proportion of in situ and invasive
      ductal carcinomas and are more prominent in invasive lobular carcinomas.

PMID- 11237490
TI  - Vascular endothelial growth factor (VEGF)--a valuable serum tumour marker in
      patients with colorectal cancer?
AB  - INTRODUCTION: Neo-angiogenesis, of great importance for tumour growth and
      nutrition, is preferentially mediated by the cytokine vascular endothelial growth
      factor (VEGF), which has a direct effect on vascular endothelial cell
      proliferation and migration. This study was designed to clarify whether VEGF is a
      suitable tumour marker in sera of patients with a colorectal cancer, and whether
      VEGF concentrations in sera and tumour tissues are correlated with tumour
      extension (pTNM) and especially with tumour volume or size. Furthermore, the
      influence of VEGF levels on patients >> prognosis was examined. METHODS: VEGF
      serum concentrations of 122 patients with colorectal cancer and 65 controls were
      determined with an ELISA kit. Additionally, VEGF concentrations of tumour and
      normal tissue were measured in 38 patients using the same ELISA. RESULTS: Our
      results demonstrate that VEGF is not a suitable diagnostic tumour marker in
      patients with colorectal cancer due to its low sensitivity (36%). However, a
      combination of the serum tumour markers CEA and VEGF can significantly increase
      the pre-operative diagnostic sensitivity to 62%. VEGF serum levels differed
      significantly between patients (mean 438 pg/ml) and controls (mean 203 pg/ml),
      and also between tumour and normal tissue (984 vs 89 pg/mg protein). Serum
      concentration showed a significant correlation to tumour volume and size.
      Patients with VEGF serum levels greater than cut-off had a poorer prognosis than
      those less than or equal to cut-off. For this reason VEGF could be used as a
      predictor of patients >> outcome.

PMID- 11237491
TI  - CEA, CA 50 and CA 242 in patients surviving colorectal cancer without recurrent
      disease.
AB  - AIMS: To establish a baseline and intraindividual fluctuations of the tumour
      markers CEA, CA 50 and CA 242 in patients cured from colorectal cancer, and to
      test the hypothesis that serum concentrations and intraindividual fluctuations do
      not differ from the concentrations in cancer-free individuals. PATIENTS AND
      METHODS: Ninety patients with colorectal cancer, who had undergone surgery with
      curative intent, were still alive at least 5 years after surgery with no signs of
      recurrent disease. Serum levels of tumour markers CEA, CA 50 and CA 242 before
      and up to 2 years after surgery were analysed after the prospective study was
      terminated. RESULTS: The pre-operative serum levels of CEA, CA 50 and CEA 242
      were elevated in 36%, 16% and 20% of the patients. They were lowered after
      curative surgery. A small increase of CEA levels was found after the initial post
      operative decrease. The intraindividual fluctuations for CA 50 and CA 242 did not
      exceed 15% but in 24% of the patients the serum levels of CA 50 were high and
      oscillating. The patients cured from Dukes >> C cancer had higher serum
      concentrations of CEA than patients who had a Dukes >> B cancer, which were
      higher than in patients who had Dukes >> A cancer. Concentrations of CA 242 were
      higher in patients cured from Dukes >> A than patients cured from Dukes>> B or C
      cancers. CONCLUSIONS: During the first 2 years after curative surgery for
      colorectal cancer the serum levels of CEA did not differ from those levels in
      normal cancer-free subjects. The serum levels of CEA were related to Dukes >>
      staging whereas the levels of CA 242 were inversely related to Dukes >> staging.

PMID- 11237492
TI  - Pseudocontinent perineal colostomy following abdominoperineal resection:
      technique and findings in 49 patients.
AB  - AIM: This prospective study was designed to evaluate functional results following
      the creation of a pseudocontinent perineal colostomy (PCPC) using Schmidt's
      technique. METHODS: Functional results in 40 patients whose rectum was resected
      due to cancer and reconstructed by PCPC between 1989 and 1995 in our institution
      were evaluated. Anatomical and pathological features of cancers, surgical
      technique and post-operative care are described. Morbidity, functional results
      and degree of patient satisfaction are reported. Median follow-up was 45 months
      (18--87 months) and was completed in 100% of patients. RESULTS: There were no
      operative deaths. Twenty patients had post-operative complications and two
      patients had an early conversion to a definitive abdominal colostomy due to
      serious perineal complications. On a functional level, four patients had normal
      continence, 23 had gas incontinence, nine had occasional minimal soiling and two
      had incontinence requiring iliac colostomy. Eighty-six per cent of patients were
      either highly satisfied or satisfied with their continence. DISCUSSION: PCPC is a
      reliable technique that can be suggested as an alternative to a left iliac
      colostomy following amputation of the rectum due to cancer, provided that certain
      requirements are met: careful selection of patients, informed consent, flawless
      surgical technique and lifetime daily colic irrigation.

PMID- 11237493
TI  - Pseudomyxoma peritonei in a hernia sac: analysis of 20 patients in whom mucoid
      fluid was found during a hernia repair.
AB  - INTRODUCTION: Pseudomyxoma peritonei syndrome is a rare disease that causes
      extensive accumulation of non-invasive mucinous tumour and mucinous fluid
      throughout the abdomen and pelvis. The primary tumour is a perforated appendiceal
      adenoma or mucinous adenocarcinoma. In patients with an open processus vaginalis
      or other peritoneal defect, the adenomatous epithelial cells may accumulate
      within the hernia sac, causing mucoid fluid to be present at the time of hernia
      repair. MATERIALS AND METHODS: From February 1991 to September 1997, the
      diagnosis of pseudomyxoma peritonei syndrome was established in 20 patients in
      whom mucoid material was found in a hernia sac during a hernia repair. Clinical
      features of these patients were critically evaluated using the completeness of
      cytoreduction as an endpoint. RESULTS: The treatments delivered at the time of
      hernia repair had no impact on the outcome. A lack of interim events vs the use
      of interim treatments between hernia repair and definitive cytoreduction was
      significant in relation to a complete vs incomplete cytoreduction. Non-aggressive
      histology and an interval of less than 1 year was statistically significantly
      associated with a favourable outcome from surgical intervention. CONCLUSION: When
      mucoid fluid is encountered at the time of a hernia repair, recovery of that
      fluid and the hernia sac for histologic study is important. When adenomatous
      epithelial cells are present, a CT scan should be performed to look for the
      typical distribution of mucinous tumour and fluid that suggests the pseudomyxoma
      peritonei syndrome. If the diagnosis can be confirmed, referral to a centre
      experienced in the treatment of this rare disease is suggested.

PMID- 11237494
TI  - Pre-clinical study of the epinephrine-cisplatin association for the treatment of
      intraperitoneal carcinomatosis.
AB  - We have previously shown that intraperitoneal (i.p.) epinephrine enhances tumour
      penetration and anti-cancer activity of i.p.-administered cisplatin in rats with
      peritoneal carcinomatosis. Here, we show a direct correlation between the i.p.
      epinephrine concentration and cisplatin accumulation in rat peritoneal tumour
      nodules up to a concentration of 5 mg/l. This concentration leads to a maximal
      3.7-fold increase of tumour platinum content and a maximal vasoconstriction of
      the peritoneal and tumour superficial microcirculation when registered by a laser
      doppler probe. Further, epinephrine half-life was 20.8+/-3.6 min in the
      peritoneal cavity of two laparotomized pigs. In these animals, epinephrine plasma
      concentration, heart rate and systolic blood pressure were dependent on the
      intraperitoneal dose of epinephrine, and life-threatening signs were not observed
      in either animal. In conclusion, a 5 mg/l concentration of epinephrine could be
      safely maintained in peritoneal fluid by regular replacement. This concentration
      is sufficient to maintain a constant vasoconstriction of the peritoneal and
      tumoral microvascular bed, and enhance the slow diffusion of cisplatin into
      peritoneal tumour nodules in the course of per-operative intraperitoneal
      chemotherapy.

PMID- 11237495
TI  - Quality of life after intraperitoneal hyperthermic chemotherapy (IPHC) for
      peritoneal carcinomatosis.
AB  - AIMS: This study assessed the functional status and quality of life (QOL) of
      patients with disseminated peritoneal cancer (DPC) before and after cytoreductive
      surgery plus intraperitoneal hyperthermic chemotherapy (IPHC). METHODS: Patients
      with confirmed or suspected diagnosis of gastro-intestinal cancer including
      stomach, pancreas, hepatobiliary and colorectal cancer with peritoneal implants
      were enrolled in the study. Sixty-four patients completed the Functional
      Assessment of Cancer Therapy-Colon (FACT-C) scale and several other instruments
      at baseline. Forty-eight, 40, 39 and 31 patients were assessed at approximately 2
      weeks post-surgery, and 3, 6 and 12 months respectively. RESULTS: There was a
      significant overall effect on the physical (P=0.0025), emotional (P<0.0001) and
      functional well-being (P=0.0044) subscales and the FACT-C (P=0.0076). Physical
      and functional well-being scores decreased at post-surgery follow-up and
      increased relative to baseline at 3, 6 and 12 months. Nineteen per cent, 46%, 59%
      and 74% of patients resumed greater than 50% of their normal activities post
      operatively at 3, 6 and 12 months respectively. A percentage of patients reported
      depressive symptoms: baseline (28%), post-operatively (33%), 3 months (23%), 6
      months (21%) and 12 months (29%). CONCLUSIONS: Cytoreductive surgery followed by
      IPHC was well tolerated. Most patients returned to baseline or better levels of
      functioning within 3 months post-treatment.

PMID- 11237496
TI  - Relevance of Ki-67 antigen expression and K-ras mutation in colorectal liver
      metastases.
AB  - AIMS: The liver is a frequent site of metastases from colorectal cancer. While
      these lesions are potentially amenable to surgical resection, they are usually
      very aggressive, and recurrence is frequent. Mutations of the proto-oncogene K-
      ras are thought to impart a strong growth signal to tumour cells and are closely
      associated with the development of malignancies of the colon and rectum. Hepatic
      metastases from colorectal cancer have notably elevated proliferative rates. The
      present study was performed to investigate the relationship between proliferation
      or K- ras mutation and prognosis following curative resection of colorectal liver
      metastases. METHODS: Colorectal liver metastases from 41 patients undergoing
      curative hepatic resection were examined for proliferation status and presence of
      K- ras mutations. The proliferative activity was assessed by Ki-67
      immunohistochemistry. DNA from the same tissue samples was screened for point
      mutations in codon 12 of the K- ras gene using a novel microplate-based allelic
      specific hybridization assay. Ki-67 scores and K- ras status were then related
      with patient survival as determined through retrospective analysis. RESULTS:
      Median survival was 40 months. Patients with high Ki-67 scores (> or = 50%) had
      significantly shorter median survival compared with those with low scores (30 vs
      44 months, log-rank P=0.02). A high Ki-67 score was an independent negative
      prognostic factor by multivariate regression analysis (relative risk=3.04,
      P=0.036). K- ras point mutations were detected in 6/41 patients (15%), but
      mutational status did not correlate with Ki-67 score or survival. CONCLUSIONS:
      These findings suggest that the tumour proliferative index is a useful predictor
      of aggressive tumour behaviour and an indicator of patient survival. The presence
      of K- ras mutations does not appear to correlate with tumour proliferation status
      or patient survival.

PMID- 11237497
TI  - Long-term prognostic significance of HSP-70, c-myc and HLA-DR expression in
      patients with malignant melanoma.
AB  - AIM: Use of molecular markers indicative of the tumour oncogenic potential and
      host response may enhance our prognostic information for more effective treatment
      of melanoma patients. The roles of HSP-70 protein, c-myc oncogene and HLA-DR
      antigen expression were examined in melanoma patients and related to prognostic
      factors, recurrence rate and long-term survival. METHODS: Forty patients with
      tumours thicker than 1 mm were included in this study. All had elective node
      dissection and were followed for at least 7 years. Twenty-two had microscopic
      nodal metastases. Both primary melanoma tumour and lymph nodes were examined for
      the immunohistochemical expression of HSP-70 protein, c-myc oncogene and HLA-DR
      antigen. RESULTS: Eighteen patients had a recurrence (45%) and 23 patients
      survived overall (57.50%). Positive HSP-70 expression was observed in 52.50% of
      the primary melanomas and was associated with improved overall survival,
      especially in the patient group with tumours > or = 1.5 mm (70%vs 26.70%,
      P=0.0159). C-myc oncogene was overexpressed in 47.50% and HLA-DR antigen in
      42.50% of the primary melanomas, but no correlation with survival was observed.
      The expression profile of these molecular markers in the primary tumour did not
      predict the status of regional nodes. HLA-DR expression in lymph nodes was
      observed exclusively in the nodal tissue surrounding the metastatic melanoma
      tumour in five patients. CONCLUSIONS: The immunohistochemical expression profile
      of HSP-70 but not of c-myc oncogene or HLA-DR antigen in the primary melanoma
      tumour could be of certain value in the identification of patients with graver
      prognosis who may benefit from more aggressive therapeutic strategies.

PMID- 11237498
TI  - Percutaneous radiological gastrostomy in patients with head and neck cancer.
AB  - AIM: To evaluate the results of percutaneous radiological gastrostomy in patients
      with head and neck cancer. PATIENTS AND METHODS: This was a retrospective study
      design. One hundred and eighteen patients with head and neck cancer were referred
      130 times for gastrostomy tube placement between 1 April 1993 and 17 August 1998.
      Mean age was 60 years. All data were analysed by using the following parameters:
      success rate, complications and mortality. Complications were divided into major,
      minor (complication that needed only conservative treatment) and tube-related.
      RESULTS: The success rate of percutaneous radiological gastrostomy was 97%. Major
      complications occurred in 6% of patients after gastrostomy tube placement. Minor
      complications occurred in 15% of patients. There was one tube-related
      complication. Procedure-related mortality occurred in one patient. The results of
      this study show no difference from those known from the literature for the
      percutaneous method and confirm that radiological gastrostomy has significantly
      lower rates of major complications than other methods of gastrostomy placement.
      CONCLUSION: Percutaneous radiological gastrostomy tube placement is, in our
      opinion, an effective and reliable method for placing a feeding tube in patients
      with head and neck cancer.

PMID- 11237500
TI  - Techniques for improving the cosmetic outcome of breast conservation surgery.
AB  - This paper presents techniques to enhance the aesthetic results of conservative
      breast surgery. A number of methods are described to improve results of
      conservative surgery by limiting deformity, reducing scars and by immediate
      replacement of tissue. By application of the appropriate technique breast tumours
      may be excised from any quadrant in a large or small breast with a good cosmetic
      outcome. Attention to detail with pre-operative planning of the estimated tissue
      loss, placement of incisions, fish-tailing of quadrantectomy scars, utilization
      of reduction mammoplasty incisions and immediate replacement of defects after
      wide excision are useful in obtaining good aesthetic results.

PMID- 11237499
TI  - A comparison of methods of loco-regional chemotherapy combined with systemic
      chemotherapy as neo-adjuvant treatment of osteosarcoma of the extremity.
AB  - AIM: Our experience of pre-operative intraarterial (i.a.) vs intravenous (i.v.)
      infusion of cisplatinum (CDP) in a multiagent neo-adjuvant chemotherapy for
      osteosarcoma of the extremity is reported. METHODS: Two successive randomized
      studies were performed. In the first, pre-operatively, CDP i.a. vs CDP i.v. was
      applied in combination with high-dose methotrexate (HDMTX) and adriamycin (ADM)
      within a three-drug regimen. In the second, a combination of HDMTX, ADM and IFO,
      within a four-drug regimen was tested. RESULTS: The rate of responses to
      chemotherapy (tumour necrosis > or = 90%) was significantly higher (P<0.04) for
      the 142 patients treated with the four-drug regimen than in the 79 patients
      treated with a three-drug regimen (76%vs 62%). According to the route of CDP
      infusion, in the three-drug regimen the rate of responses was significantly
      higher (P=0.004) in patients treated with i.a. CDP (77%) than in patients treated
      i.v. (46%); with the four-drug regimen the rate of response was not significantly
      different in patients treated i.a. (81%) and in patients treated i.v. (71%). No
      significant differences in the rates of limb salvages, local recurrence and event
      free survival (EFS) were seen between the i.a. and the i.v. groups. CONCLUSION:
      In the treatment of osteosarcoma of the extremity, the i.a. infusion of CDP does
      not offer any significant advantage when this drug is used within an aggressive,
      multiagent, pre-operative four-drug regimen.

PMID- 11237501
TI  - The sentinel node in anal carcinoma.

PMID- 11237502
TI  - Primary pheochromocytoma extending into the right atrium: report of a case and
      review of the literature.
AB  - Pheochromocytoma rarely extends locally into the vena cava or the right atrium.
      We report a case of malignant pheochromocytoma with growth into the inferior vena
      cava, extending into the right atrium, address clinical aspects of this tumour
      and review the literature on this malignancy. Pre-operative work-up of this
      tumour should include measurements of urinary vanillyl mandelic acid and
      cathecholamine excretion, MRI and spiral CT of the abdomen and thorax. After the
      diagnosis is made the patient should be treated with catecholamine alpha-receptor
      blockade and if necessary with subsequent beta-receptor blockade. An aggressive
      surgical approach is always warranted, even in cases with very large localized
      tumours, because surgery has been shown to lead to relief of symptoms and to
      prolong survival in cases otherwise deemed irresectable. The optimal surgical
      exposure is obtained via a transsternal midline thoraco-laparotomy. If feasible,
      a combination of cardiopulmonary bypass, hypothermia, cardiac arrest and
      exsanguination procedures should be used. In case of local of tumour remnants
      after surgery or distant metastases treatment options are secondary surgery,
      tumour embolization, or treatment with radioactive labelled drugs,
      including(131)I-MIBG.

PMID- 11237503
TI  - Cervical lymphadenopathy as metastases from a scalp secondary: a 'double
      metastasis'.

PMID- 11237504
TI  - A rare tumour in the pelvis presenting with lower urinary symptoms: 'sclerosing
      epithelioid fibrosarcoma'.

PMID- 11237505
TI  - Delta-aminolevulinate dehydratase polymorphism and blood lead levels in Chinese
      children.
AB  - This study investigated the relationship between the delta-aminolevulinate
      dehydratase (ALAD) isozymes and the blood lead levels of Chinese children. The
      purpose of this study was to determine the precise ALAD genotyping in Chinese
      children and identify the contribution of the ALAD genotype to the body lead
      burden. Blood samples were obtained from 109 boys and 120 girls. These children
      were 6-10 years old and from a single primary school. Both the school and their
      homes were within a community in which a large smelter was located. An
      environmental questionnaire was obtained for each subject, and blood lead levels
      and ALAD isozyme phenotype were analyzed in a double-blinded fashion. The blood
      lead levels of 229 children ranged from 4.5 to 26.4 microg/dl; the mean was 10.3
      microg/dl and the standard deviation was 3.3 microg/dl. The gene distribution of
      the ALAD isozyme phenotypes in these environmentally exposed children was ALAD 1
      1 (92%), ALAD 1-2, (8%), and ALAD 2-2 (0%). The mean blood level of the
      environmentally exposed children, who were homozygous for the ALAD1 allele, was
      9.7 microg/dl; the mean for those who were heterozygous for the ALAD2 allele was
      11.7 microg/dl. Using the t test, the means of the groups were different at the
      level of t=2.2058, P<0.05. Step-wise regression and multiple analyses of
      covariance were employed to control the confounders to measuring the independent
      contribution of the ALAD genotype on blood lead levels. After controlling the
      confounders, the contribution of the ALAD genotype to the blood lead level was
      greater and still statistically significant (F=7.3201, P<0.01). These results
      indicate that individuals carrying the ALAD2 allele are more likely to have
      sustained increases in blood lead levels when exposed to a lead-contaminated
      environment.

PMID- 11237506
TI  - Seasonal variation in bone lead contribution to blood lead during pregnancy.
AB  - Population blood lead level (PbB) often shows seasonal variation, frequently
      being higher in summer and lower in winter. As vitamin D metabolites also show
      seasonal variability, and the metabolites are associated with bone metabolism,
      some authors have posited a role for bone lead release in seasonal PbB changes.
      We made third trimester and postdelivery PbB measurements on 414 immigrant women
      (98% Latina) in Los Angeles. We measured in vivo tibia and calcaneus (heel) lead
      concentration postdelivery via K-shell X-ray fluorescence. We saw evidence of
      seasonal variation in prenatal PbB, but not postnatal PbB. PbB was highest in
      spring and lowest in autumn. Tibia lead concentration was associated with
      prenatal PbB, as reported before. The contribution of tibia lead to prenatal PbB
      varied seasonally, with the greatest contribution occurring in the winter quarter
      and the least in the summer quarter. The temporal pattern of bone lead
      contribution to PbB follows the seasonal alteration of insolation. There was no
      seasonal component in prenatal PbB associated with calcaneus lead, nor were there
      seasonal variations in either calcaneus or tibia lead contributions to postnatal
      PbB. Bone turnover in the third trimester of pregnancy may be higher in winter
      months than in summer months, resulting in greater fetal lead exposure in spring
      than at other times of the year.

PMID- 11237507
TI  - Adverse health effects among household waste collectors in Taiwan.
AB  - Household waste collectors (HWCs) are potentially exposed to a variety of
      bioaerosols and toxic materials. Collection of household waste is also a job
      which requires repeated heavy physical activity such as lifting, carrying,
      pulling, and pushing. The object of this study was to assess whether there is an
      excess of adverse health outcomes among HWCs. The subjects were all current
      employees of the Household Waste Collection Department in the County of
      Kaohsiung, Taiwan. The survey questionnaire was completed by 533 HWCs and 320
      office workers. Our data indicate that household waste collection presents a risk
      for the development of chronic respiratory symptoms (cough, phlegm, wheezing, and
      chronic bronchitis), musculoskeletal symptoms (low back pain and elbow/wrist
      pain), and injuries caused by sharp objects.

PMID- 11237508
TI  - Environmental illness: fatigue and cholinesterase activity in patients reporting
      hypersensitivity to electricity.
AB  - The lack of a pathophysiological marker hinders studies on environmental
      illnesses of unknown origin. Hence, research focused on the identification of
      such a marker is a priority. This study investigated the nature and a possible
      etiology of fatigue in hypersensitivity to electricity (the most commonly
      reported environmental illness in Sweden). The aim was to test the hypothesis
      that perceived fatigue was due to alterations in cholinesterase activity. The
      study group consisted of 14 people who reported a hypersensitivity to
      electricity, including disabling fatigue. We assessed cholinesterase activity
      three times: twice based on current symptoms reported by the subjects (severe
      fatigue attributed to electromagnetic fields and absence of this symptom) and
      once at a randomly selected time. No significant reduction in
      acetylcholinesterase was identified in any subject. Examined on a group level, no
      significant reduction in activity was identified at the time of severe fatigue,
      and no correlation between reported degree of fatigue and cholinesterase activity
      was observed. Fatigue attributed to electromagnetic fields was nonphysical and
      showed a significant correlation to difficulties in concentrating. The results do
      not support the hypothesis that a change in cholinesterase activity mediates
      fatigue in people reporting hypersensitivity to electricity.

PMID- 11237509
TI  - Differential responses of rat alveolar and peritoneal macrophages to man-made
      vitreous fibers in vitro.
AB  - Different approaches, including inhalation and intraperitoneal injection assays,
      have been used to assess the potential health effects of man-made vitreous fibers
      (MMVF). The purpose of this study was to compare the phagocytic activity and the
      formation of reactive oxygen species by rat alveolar macrophages (AM) and
      peritoneal macrophages (PM) upon exposure to MMVF10 glass wool and MMVF21 rock
      wool fibers. Macrophage (Mphi) phagocytosis of mineral fibers was assessed by
      optical videomicroscopy and computer-aided image analysis. Mphi were classified
      as cells not associated with fibers, cells with attached fibers, cells with
      incompletely phagocytized fibers (an appearance known as "frustrated
      phagocytosis"), and cells with completely phagocytized fibers. The production of
      superoxide anions by AM and PM upon incubation with MMVF10 and MMVF21 fibers was
      determined by the superoxide dismutase-inhibitable reduction of ferricytochrome
      C. PM were found to have a lower phagocytic activity than AM. A significantly
      higher percentage of AM than of PM underwent frustrated phagocytosis of MMVF10
      and MMVF21 fibers. In line with these findings, AM generated higher levels of
      oxygen radicals than PM upon exposure to MMVF21 fibers. In contrast, MMVF10
      fibers failed to induce the generation of reactive oxygen species by both AM and
      PM. Our in vitro results show that the phagocytic activity, in particular the
      frustrated phagocytosis of mineral fibers, was significantly lower in PM than in
      AM. The data support the idea that the durability and biopersistence of mineral
      fibers are higher in the peritoneal cavity than in the lung.

PMID- 11237510
TI  - Mineral status of female rats affects the absorption and organ distribution of
      dietary cadmium derived from edible sunflower kernels (Helianthus annuus L.).
AB  - The intake of food cadmium (Cd) in microg/day over time can increase the body
      burden of this element. Some human populations that consume subsistence rice
      based diets low in calcium (Ca), iron (Fe), and zinc (Zn) are more susceptible to
      Cd poisoning than populations that consume more nutritious diets. This study
      determined the effects of marginal deficiencies of these essential elements on
      the absorption and organ retention of Cd from a natural food that contains Cd,
      edible sunflower kernels (Helianthus annuus L.; SFK). Weanling female rats were
      fed diets containing 20% SFK in a 2x2x2 factorial design with marginal and
      adequate amounts of Ca, Zn, and Fe. Marginal Zn (11 mg/kg) and Fe (13 mg/kg), and
      Cd (0.18 mg/kg) were derived solely from 20% SFK. These amounts of Fe and Zn
      represented 39 and 90% of the NRC requirement for the rat, respectively. The
      marginal dietary Ca concentration (2.5 g/kg) was one-half the NRC requirement.
      After 5 weeks on the experiment, rats were fed 1 g of their respective diets
      containing SFK extrinsically labeled with 37 kBq 109Cd, and absorption was
      determined by whole-body counting techniques. Rats were then killed and organs
      collected for 109Cd assays. No effect of treatment on weight gain was observed;
      however, when dietary Zn was low, feeding marginal Ca elevated Cd absorption by
      50% (P<0.05) over those fed adequate Ca and Zn. Feeding marginal Fe elevated Cd
      absorption >2.5-fold (P<0.001) over those fed adequate Fe. In contrast, the
      naturally occurring Zn in SFK that provided 90% of the rat's requirement was
      enough to deter excessive absorption of Cd and enough to alone prevent
      significant elevation of organ Cd. Organ content of 109Cd and Cd followed the
      same general pattern as whole-body absorption. These data show that marginal
      nutritional deficiencies of Ca and Fe can readily enhance the body burden of Cd
      that comes from the diet. Also, some natural competitors of Cd, such as Zn,
      contained in foods can independently minimize Cd absorption.

PMID- 11237511
TI  - Effect of the herbicide glyphosate on enzymatic activity in pregnant rats and
      their fetuses.
AB  - To prevent health risk from environmental chemicals, particularly for progeny, we
      have studied the effects of the herbicide glyphosate on several enzymes of
      pregnant rats. Glyphosate is an organophosphorated nonselective agrochemical
      widely used in many countries including Argentina and acts after the sprout in a
      systemic way. We have studied three cytosolic enzymes: isocitrate dehydrogenase
      NADP dependent, glucose-6-phosphate dehydrogenase, and malic dehydrogenase in
      liver, heart, and brain of pregnant Wistar rats. The treatment was administered
      during the 21 days of pregnancy, with 1 week as an acclimation period. The
      results suggest that maternal exposure to agrochemicals during pregnancy induces
      a variety of functional abnormalities in the specific activity of the enzymes in
      the studied organs of the pregnant rats and their fetuses.

PMID- 11237513
TI  - Preliminary description of antigenic components characteristic of Stachybotrys
      chartarum.
AB  - The objective of this study was to characterize preliminarily immunogenic
      components characteristic of Stachybotrys chartarum to be used later for the
      development of a detection method for the fungus in environmental samples. The
      procedure for S.chartarum extract preparation was first optimized related to the
      age of the culture, culture type, and growth medium, and the antigenic
      composition of S. chartarum cultured in two different media was then
      characterized by the sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE) and immunoblotting method. Cross-reactivity of S. chartarum antigenic
      components with 10 other fungal species was identified by the inhibition
      immunoblotting method. The 10-day-old S. chartarum culture extract cultured in
      malt extract broth revealed a wider selection of proteins and antigenic
      components than the 30-day-old culture extract or the culture medium extracts.
      When cultured in cellulose broth, S. chartarum produced a higher number of
      proteins and antigenic components than in malt extract broth. The most dominant
      immunogenic components of S. chartarum cultured in cellulose broth were those of
      65, 50, 37, and 27 kDa. The components of 65 and 50 kDa proved to be the most
      characteristic of this fungus according to the inhibition immunoblotting
      analyses. Several of the S. chartarum components were identified as
      glycoproteins. Carbohydrate moieties of the S. chartarum components also
      possessed an antibody binding activity.

PMID- 11237512
TI  - Longitudinal study of daily intake and excretion of lead in newly born infants.
AB  - As an adjunct to a study of lead mobilization during pregnancy and lactation, we
      have obtained estimates of the daily lead intake and excretion/intake for 15
      newly born infants monitored for at least 6 months postpartum. The longitudinal
      data presented reflect the far lower levels of environmental contribution to lead
      in blood in the 1990's than that in the earlier studies from the 1970's and early
      1980's, the last period for which such dietary information is available in newly
      born infants. Infants were breast-fed or formula-fed or both and, in the second
      quarter, were usually fed solid foods (beikost). Lead concentrations were as
      follows: lead in breast milk, ranged from 0.09 to 3.1 microg/kg with a geometric
      mean of 0.55 microg/kg, lead in infant formula ranged from 0.07 to 11.4 microg/kg
      with a geometric mean of 1.6 microg/kg, and lead in beikost ranged from 1.1 to 27
      microg/kg with a geometric mean of 2.9 microg/kg. Daily lead intakes ranged from
      0.04 to 0.83 microg/kg body weight/day with a geometric mean of 0.23 microg Pb/kg
      body weight/day, and excretion/intake ranged from 0.7 to 22 with a geometric mean
      of 2.6. There was no significant difference at the 5% level in lead concentration
      in daily intakes and excretion/intake for the first quarter versus the second
      quarter for this small number of subjects. Assuming that there was no
      contribution from environmental samples such as house dust and ambient air, the
      contribution of diet to blood has been estimated from lead isotopic measurements
      with the following ranges: for breast milk only as the dietary source, 40 to 65%;
      for breast milk and infant formula as the dietary sources, 15 to 70%; and for
      infant formula and beikost, 20 to 80%. The geometric mean value of the dietary
      contribution to blood over the 6-month period of approximately 35% is consistent
      with earlier estimates of uptake of lead in blood in newly born infants when
      environmental lead concentrations were much higher. Other sources such as air,
      soil, and dust are considered to contribute minimally to blood lead in these
      infants because of the low 206Pb/204Pb ratios in environmental media. Thus, we
      consider that the increased excretion over intake, along with other evidence,
      reflects mobilization of infant tissues arising especially from rapid bone
      turnover at this stage of life; the tissue lead has been identified isotopically
      in urine.

PMID- 11237514
TI  - Pesticide use by persons who reported a high pesticide exposure event in the
      agricultural health study.
AB  - Almost 16% of the pesticide applicators in the Agricultural Health Study (AHS)
      cohort (a cohort that includes 52,629 private applicators) reported having a high
      pesticide exposure event (i.e., an incident or experience while using a pesticide
      that caused an unusually high personal exposure). Pesticides involved in these
      events were compared to the frequency with which specific pesticides were ever
      used by the AHS cohort. Generally, pesticides with greater acute toxicity were
      more frequently involved with the high pesticide exposure event than were other
      pesticides. Whereas it is clear that the use of acutely toxic pesticides may be
      related to more frequent visits to health care facilities, the reason that the
      spills and immersions of the high pesticide exposure events are associated with
      the acute toxicity of the pesticide is not intuitively clear. This analysis
      suggests that current practices directed at minimizing pesticide exposures may
      not be sufficient for acutely toxic or irritating chemicals.

PMID- 11237515
TI  - Radioactive and conventional pollutants accumulated by edible mushrooms (Boletus
      sp.) are useful indicators of species origin.
AB  - Concentrations of artificial radionuclides and trace elements in Boletus samples
      collected in different areas of the world were detected, respectively, by gamma
      spectrometry and neutron activation analysis. The particular commercial value of
      Boletus edulis, B. aestivalis, and B. pinophilus from the Taro Valley (Parma,
      Italy) has often stimulated local factories to trade edible Boletus imported from
      several areas of the world as the real Taro Valley mushroom. Starting from this
      evidence, the calculation of the Chernobyl radioactive contamination in the
      mushrooms coupled with the presence of particular stable elements and their
      concentration factors has been demonstrated to be a potential useful tool for
      identifying the real origin of the samples. In fact, major differences in the
      radiocesium activity levels and trace element presence were observed even in
      mushrooms collected in nearby valleys. The radiometric data are supported by the
      statistical analysis. In particular, both the principal component analysis and
      the concentration distribution along a regression line support the idea of two
      different clusters: one referred to the "king boletus" of the Taro Valley and
      another one to the other conspecific samples from different ecosystems.

PMID- 11237516
TI  - Fine-scale tissue distribution of cadmium, inorganic mercury, and methylmercury
      in nymphs of the burrowing mayfly Hexagenia rigida studied by whole-body
      autoradiography.
AB  - The distribution of inorganic 109Cd(II), inorganic 203Hg(II), and [203Hg]
      methylmercury (MeHg) in nymphs of the burrowing mayfly Hexagenia rigida after
      exposure via water and sediments was studied. To better understand the mechanisms
      underlying the fate of Cd, Hg, and MeHg in this animal and to identify target
      organs, autoradiography of whole-body cryosections was used to obtain a detailed
      view of the distribution of the radiolabels. The gut and exoskeleton were the
      only structures labeled in nymphs exposed to Cd via water or sediments. After
      exposure to inorganic Hg via water, the Malpighian tubules exhibited a very high
      labeling, indicating that these organs may be a target for Hg toxicity. The
      distribution of Hg after exposure via sediments was similar, though the labeling
      of Malpighian tubules was less intense. Distribution of MeHg strongly differed
      between treatment groups. Nymphs were rather uniformly labeled after exposure via
      water, whereas in those exposed to MeHg in sediments, the intense labeling of all
      internal tissues contrasted with the very low labeling of the hemolymph,
      indicating that the translocation rate of the absorbed MeHg was faster in the
      latter group. This may be related to the complexation of MeHg by small thiol
      ligands in the gut as a result of the digestion process.

PMID- 11237518
TI  - Tumor suppressor perspective.

PMID- 11237519
TI  - The retinoblastoma gene: a prototypic and multifunctional tumor suppressor.
AB  - Genome instability has been implicated in the generation of multiple somatic
      mutations that underlie cancer. Germline mutation in the retinoblastoma (RB) gene
      leads to tumor formation in both human and experimental animal models, and
      reintroduction of wild-type RB is able to suppress neoplastic phenotypes. Rb
      governs the passage of cells through the G1 phase-restriction point and this
      control is lost in most cancer cells. Rb has also been shown to promote terminal
      differentiation and prevent cell cycle reentry. Recent studies implicate Rb in
      mitotic progression, faithful chromosome segregation, checkpoint control, and
      chromatin remodeling, suggesting that Rb may function in the maintenance of
      genome integrity. It is likely that Rb suppresses tumor formation by virtue of
      its multiple biological activities. A single protein capable of performing
      multiple antioncogenic functions may be a common characteristic of other tumor
      suppressors including p53 and BRCA1/2.

PMID- 11237520
TI  - Neurofibromin, a tumor suppressor in the nervous system.

PMID- 11237521
TI  - PTEN: life as a tumor suppressor.
AB  - PTEN, a tumor suppressor located at chromosome 10q23, is mutated in a variety of
      sporadic cancers and in two autosomal dominant hamartoma syndromes. PTEN is a
      phosphatase which dephosphorylates phosphatidylinositol (3,4,5)-triphosphate
      (PtdIns-3,4,5-P3), an important intracellular second messenger, lowering its
      level within the cell. By dephosphorylating PtdIns-3,4,5-P3, PTEN acts in
      opposition to phosphatidylinositol 3-kinase (PI3K), which has a pivotal role in
      the creation of PtdIns-3,4,5-P3. PtdIns-3,4,5-P3 is necessary for the activation
      of Akt, a serine/threonine kinase involved in cell growth and survival. By
      blocking the activation of Akt, PTEN regulates cellular processes such as cell
      cycling, translation, and apoptosis. In this review, we will discuss the
      identification of PTEN, its mutational status in cancer, its role as a regulator
      of PI3K, and its domain structure.

PMID- 11237522
TI  - p16(MTS-1/CDKN2/INK4a) in cancer progression.
AB  - Since its discovery as an inhibitor of cyclin-dependent kinases 4 and 6, the
      tumor suppressor p16 has continued to gain widespread importance in cancer. The
      high frequency of deletions of p16 in tumor cell lines first suggested an
      important role for p16 in carcinogenesis. This initial genetic evidence was
      subsequently strengthened by numerous studies documenting p16 inactivation in
      kindreds with familial melanoma. Moreover, a high frequency of p16 gene
      alterations was found in primary tumors, while recent studies have identified p16
      promoter methylation as a major mechanism of tumor-suppressor-gene silencing.
      Additional insight into p16's role in cancer has come from the genetic analysis
      of precancerous lesions and various tissue culture models. It is now believed
      that loss of p16 is an early and often critical event in tumor progression.
      Consequently, p16 is a major tumor-suppressor gene whose frequent loss occurs
      early in many human cancers.

PMID- 11237523
TI  - Regulation of p53 function.

PMID- 11237524
TI  - Interactions between BRCA proteins and DNA structure.

PMID- 11237525
TI  - Wilms tumor and the WT1 gene.
AB  - Wilms tumor or nephroblastoma is a pediatric kidney cancer arising from
      pluripotent embryonic renal precursors. Multiple genetic loci have been linked to
      Wilms tumorigenesis; positional cloning strategies have led to the identification
      of the WT1 tumor suppressor gene at chromosome 11p13. WT1 encodes a zinc finger
      transcription factor that is inactivated in the germline of children with genetic
      predisposition to Wilms tumor and in a subset of sporadic cancers. When present
      in the germline, specific heterozygous dominant-negative mutations are associated
      with severe abnormalities of renal and sexual differentiation, pointing to the
      essential role of WT1 for normal genitourinary development. The role of this
      tumor suppressor in normal organ-specific differentiation is also supported by
      the highly restricted temporal and spatial expression of WT1 in glomerular
      precursors of the developing kidney and by the failure of kidney development in
      wt1-null mice. Of two major alternative splicing products encoded by WT1, the (
      KTS) isoform appears to mediate transcriptional activation of genes implicated in
      cellular differentiation, possibly also repressing proliferation-associated
      genes. The (+KTS) isoform, whose DNA-binding domain is disrupted by the insertion
      of three amino acids, may be involved in some aspect of mRNA processing. In
      addition to its function in genitourinary development, a role for WT1 in
      hematopoiesis is suggested by its aberrant expression and/or mutation in a subset
      of acute human leukemias. WT1 is also expressed in mesothelial cells; a specific
      oncogenic chromosomal translocation fusing the N-terminal domain of the Ewing
      sarcoma gene EWS to the three C-terminal zinc fingers of WT1 underlies
      desmoplastic small round cell tumor, an abdominal tumor thought to arise from the
      peritoneal lining. Understanding the distinct functional properties of WT1
      isoforms and tumor-associated variants will provide unique insight into the link
      between normal organ-specific differentiation and malignancy.

PMID- 11237526
TI  - Mouse models for sporadic cancer.
AB  - Much of the advancement in mouse models for cancer during the past 2 decades can
      be attributed to our increasing capacity to specifically modify the mouse germ
      line. The first generations of oncomice and tumor-suppressor gene knockouts are
      now being succeeded by regulatable or conditional mouse tumor models, which can
      be utilized more effectively to establish correlations between distinct genetic
      lesions and specific tumor characteristics and to design and improve therapeutic
      intervention strategies. In this review we try to give the reader a flavor of how
      the latest reagents can be utilized.

PMID- 11237527
TI  - TGFbeta signaling and cancer.

PMID- 11237528
TI  - The von Hippel-Lindau tumor suppressor gene.
AB  - Germline mutations of the von Hippel-Lindau tumor suppressor gene (VHL) in humans
      causes a hereditary cancer syndrome characterized by the development of retinal
      and central nervous system hemangioblastomas. Other tumors associated with von
      Hippel-Lindau disease include clear cell renal carcinomas and pheochromocytomas.
      Tumor development in this setting is due to functional loss of the remaining wild
      type VHL allele. Biallelic VHL inactivation is also common in nonhereditary
      hemangioblastomas and clear cell renal carcinomas, in keeping with Knudson's 2
      Hit Model of carcinogenesis. The VHL gene product, pVHL, is a component of an E3
      ubiquitin ligase that targets the alpha subunits of the HIF (hypoxia-inducible
      factor) transcription factor for destruction in the presence of oxygen.
      Consequently, tumor cells lacking pVHL overproduce the products of HIF target
      genes such as vascular endothelial growth factor and transforming growth factor
      alpha. pVHL has been implicated in a variety of processes that are central to
      carcinogenesis including cell-cycle control, differentiation, extracellular
      matrix formation and turnover, and angiogenesis.

PMID- 11237529
TI  - The many faces of the tumor suppressor gene APC.
AB  - Inactivation of the tumor suppressor adenomatous polyposis coli (APC) protein is
      a critical early step in the development of familial and sporadic colon cancer.
      Close examination of the function of APC has shown that it is a multifunctional
      protein involved in a wide variety of processes, including regulation of cell
      proliferation, cell migration, cell adhesion, cytoskeletal reorganization, and
      chromosomal stability. Tantalizing clues to the different functions of APC have
      been provided by the identification of proteins interacting with several discrete
      motifs within APC. Each of these putative functions could link APC inactivation
      with tumorigenesis. Here, we will summarize recent findings regarding the diverse
      role of APC. We will emphasize the interaction of APC with different binding
      partners, the role of these complex interactions for normal functioning of the
      cell, and how disruption of these interactions may play a role in tumor
      development. The rapid progress made recently shows the many faces of APC,
      leading to a constant reappreciation of this multitasking tumor suppressor
      protein.

PMID- 11237530
TI  - p107 and p130: versatile proteins with interesting pockets.
AB  - p107 and p130 were originally identified as targets of the transforming domains
      of viral oncoproteins encoded by small DNA tumor viruses. Together with pRB, the
      protein product of the retinoblastoma gene (Rb), p107 and p130 represent a family
      of closely related proteins that play critical roles in the regulation of cell
      proliferation. p107, p130, and pRB are transcriptional regulators whose
      activities are coupled to the cell cycle. Each of these proteins associates with
      E2F and is directly regulated by phosphorylation by cyclin-dependent kinases. In
      vivo studies of p107 and p130 function have revealed that their roles overlap
      extensively with one another and with pRB. In addition, the analysis of mice (and
      cell lines derived from these animals) deficient in these proteins shows that the
      individual members of this family harbor distinct functions that, at present, are
      poorly understood. The characterization of tumor cells continues to emphasize the
      important and somewhat unique role of pRB in tumor suppression, and the evidence
      linking the specific inactivation of p107 or p130 to tumor development remains
      quite limited. In this review we summarize the biochemical and functional
      properties of p107 and p130, and we compare and contrast these properties to
      those of pRB.

PMID- 11237531
TI  - p27(Kip1): regulation and function of a haploinsufficient tumor suppressor and
      its misregulation in cancer.
AB  - A major function of p27, also known as Kip1, is to bind and inhibit cyclin/cyclin
      dependent kinase complexes, thereby blocking cell cycle progression. As p27
      operates at the heart of the cell cycle, it is perhaps not surprising that it is
      emerging as a key player in multiple cell fate decisions including proliferation,
      differentiation, and cell death. The central role of p27 makes it important in a
      variety of disease processes that involve aberrations in cellular proliferation
      and other cell fates. Most notable among these processes is neoplasia. A large
      number of studies have reported that p27 expression is frequently downregulated
      in human tumors. In most tumor types, reduced p27 expression correlates with poor
      prognosis, making p27 a novel and powerful prognostic marker. In addition to
      these practical implications, murine and tissue culture models have shown that
      p27 is a potent tumor suppressor gene for multiple epithelially derived
      neoplasias. Loss of p27 cooperates with mutations in several oncogenes and tumor
      suppressor genes to facilitate tumor growth, indicating that p27 may be a "nodal
      point" for tumor suppression. In contrast to most tumor suppressor genes studied
      to date, which are recessive at the cellular level, p27 is haploinsufficient for
      tumor suppression. The fact that tumor suppression by p27 is critically dependent
      on the absolute level of p27 expression indicates that p27 acts as a rheostat
      rather than as an on/off switch to control growth and neoplasia.

PMID- 11237532
TI  - Heterotypic signaling between epithelial tumor cells and fibroblasts in carcinoma
      formation.
AB  - Tumors arise from cells that have sustained genetic mutations resulting in
      deregulation of several of their normal growth-controlling mechanisms. Much of
      the research concerning the origins of cancer has focused on the genetic
      mutations within tumor cells, treating tumorigenesis as a cell-autonomous process
      governed by the genes carried by the tumor cells themselves. However, it is
      increasingly apparent that the stromal microenvironment in which the tumor cells
      develop profoundly influences many steps of tumor progression. In various
      experimental tumor models, the microenvironment affects the efficiency of tumor
      formation, the rate of tumor growth, the extent of invasiveness, and the ability
      of tumor cells to metastasize. In carcinomas, the influences of the
      microenvironment are mediated, in large part, by paracrine signaling between
      epithelial tumor cells and neighboring stromal fibroblasts. In this review, we
      summarize recent advances in understanding the paracrine signaling interactions
      between epithelial cancer cells and associated fibroblasts and examine the
      effects of these bidirectional interactions on various aspects of carcinoma
      formation. We note, however, that paracrine signaling between other cell types
      within the carcinomas, such as endothelial cells and inflammatory cells, may play
      equally important roles in tumor formation and we will refer to these heterotypic
      interactions where relevant.

PMID- 11237533
TI  - DAP kinase-a proapoptotic gene that functions as a tumor suppressor.

PMID- 11237534
TI  - Hormone replacement therapy: where we stand in Europe.

PMID- 11237535
TI  - Reverse cholestrol transport substantially influences the individual risk of
      coronary heart disease in hypercholesterolaemic patients.

PMID- 11237536
TI  - The management of cardiogenic shock: can anything be learnt from registries?

PMID- 11237537
TI  - The 6-minute walk test and prognosis in chronic heart failure--the available
      evidence.

PMID- 11237538
TI  - Early repolarization syndrome and the Brugada syndrome: forme frustes?

PMID- 11237539
TI  - How should we detect and manage failed thrombolysis?

PMID- 11237540
TI  - Treatment of tachyarrhythmias during pregnancy and lactation.

PMID- 11237541
TI  - Importance of HDL cholesterol levels and the total/ HDL cholesterol ratio as a
      risk factor for coronary heart disease in molecularly defined heterozygous
      familial hypercholesterolaemia.
AB  - AIMS: To assess the relationship of the lipid profile to coronary heart disease
      in a group of heterozygous familial hypercholesterolaemic subjects with similar
      age, sex, body mass index, prevalence of angiotensin converting enzyme DD
      genotype and type of low density lipoprotein receptor mutation. METHODS AND
      RESULTS: A total of 66 molecularly defined heterozygous familial
      hypercholesterolaemic subjects, 33 of whom had coronary heart disease, were
      studied. Clinical features, cardiovascular risk factors and lipid parameters were
      compared in both groups. Familial hypercholesterolaemic patients with coronary
      heart disease showed significantly lower values of mean plasma HDL cholesterol
      and a higher total/HDL cholesterol ratio as compared with familial
      hypercholesterolaemic subjects free of coronary heart disease. Total and LDL
      cholesterol concentrations were higher in patients with coronary heart disease,
      without reaching statistical significance. No differences in plasma
      lipoprotein(a) levels on absolute and log-transformed values were observed
      between the two groups. In the whole familial hypercholesterolaemia group, plasma
      HDL cholesterol levels were related to plasma triglyceride values and to LDL
      receptor gene 'null mutations'. CONCLUSIONS: In familial hypercholesterolaemic
      subjects of similar age, gender, body mass index, systolic and diastolic blood
      pressure, and genetic factors that could influence coronary heart disease risk,
      plasma HDL cholesterol values and total/HDL cholesterol ratios are two important
      coronary risk factors. Hence, treatment of familial hypercholesterolaemia should
      focus not only on lowering total and LDL cholesterol levels, but also on
      increasing HDL cholesterol values for coronary heart disease prevention. More
      prospective and intervention trials should be conducted to establish the
      relationship of HDL cholesterol levels and coronary heart disease in familial
      hypercholesterolaemia.

PMID- 11237542
TI  - Trends in cardiogenic shock: report from the SHOCK Study. The SHould we
      emergently revascularize Occluded Coronaries for cardiogenic shocK?
AB  - AIMS: We analysed time trends in patient characteristics, management, and
      outcomes of cardiogenic shock complicating acute myocardial infarction in the
      international, prospective SHOCK Trial Registry and pre-study Registry.
      BACKGROUND: Despite therapeutic advances in its management, the incidence and
      high mortality of this complication has remained unchanged for decades. However,
      in recent years mortality was reported to decrease in one community concomitant
      with increasing use of revascularization. METHODS: Thirty-six centres registered
      1380 patients with suspected cardiogenic shock complicating acute myocardial
      infarction from January 1992 to August 1997. Patient and myocardial infarction
      characteristics, haemodynamics, medications, procedure use, and vital status at
      discharge were recorded. RESULTS: In all, 79% of patients had shock due to
      predominant pump failure (non-mechanical aetiology). The aetiology, patient
      profile, and clinical characteristics of cardiogenic shock did not differ over
      time, except for increases in the incidence of prior bypass surgery (P=0.054) and
      transfers to tertiary centres (P=0.008). In all, 44% underwent revascularization
      (n=485), with angioplasty performed more often than bypass surgery (69% vs 31%).
      The revascularization rate increased over time (P=0.006) with a significant
      decrease in the time to revascularization (P=0.033). The use of Swan-Ganz
      catheterization decreased over time (P=0.018), as did the mean length of
      hospitalization (P=0.034). Overall in-hospital mortality was high (63%) but
      decreased over time in all patients (P=0.004) and those with pump failure
      (P=0.018). Mortality was lower for patients who underwent revascularization
      compared to those who were not revascularized (41% vs 79%, P<0.001). CONCLUSIONS:
      Cardiogenic shock complicating acute myocardial infarction is associated with a
      high mortality rate, but mortality decreased significantly from 1992 to 1997.
      This partly reflects the greater use of revascularization, which was associated
      with better outcomes. The reported international trend towards shorter admissions
      for myocardial infarction was also observed in this cohort.

PMID- 11237543
TI  - Coronary flow reserve in angiographically normal coronary arteries with one
      vessel coronary artery disease without traditional risk factors.
AB  - AIMS: Reduced coronary flow reserve has been reported in patients with
      traditional risk factors, in particular hyperlipidaemia, despite angiographically
      normal coronary arteries. However, it is recognized that traditional risk factors
      do not explain the presence of coronary atherosclerosis in a large proportion of
      patients. The aim of this study was to assess whether coronary flow reserve is
      preserved in the myocardium supplied by normal coronary arteries in patients with
      one-vessel coronary artery disease without traditional risk factors. METHODS AND
      RESULTS: Positron emission tomography using [13N]ammonia was performed at
      baseline and after intravenous dipyridamole administration (0.56 mg x dl(-1)over
      4 min) in 30 subjects: six patients with ischaemia on effort, no myocardial
      infarction, and isolated left anterior descending coronary artery stenosis
      without traditional risk factors (coronary artery disease patients without risk
      factors, aged 59+/-13), five patients with ischaemia on effort, no myocardial
      infarction, and isolated left anterior descending coronary artery stenosis with
      multiple risk factors (coronary artery disease patients with risk factors, aged
      69+/-7), 11 age-matched controls (aged 58+/-6), and eight healthy young
      volunteers (aged 34+/-4). Myocardial blood flow calculated in the myocardium
      supplied by normal coronary arteries in the coronary artery disease patients was
      compared with those of the two control groups. Coronary flow reserve was defined
      as the ratio of hyperaemic blood flow after dipyridamole infusion to baseline
      blood flow. Although coronary flow reserve in the coronary artery disease
      patients with risk factors was significantly lower than that in the age-matched
      controls (1.62+/-0.37, 2.58+/-0.71, P=0.0428), coronary flow reserve in the
      coronary artery disease patients without risk factors was similar to that in the
      age-matched controls (2.54+/-0.17 vs 2.58+/-0.71, P=ns). CONCLUSION: Coronary
      flow reserve is preserved in regions supplied by angiographically normal coronary
      arteries with one-vessel coronary artery disease without traditional risk
      factors.

PMID- 11237544
TI  - Six-minute walking performance in patients with moderate-to-severe heart failure;
      is it a useful indicator in clinical practice?
AB  - AIMS: The 6-min walk test has been incorporated into studies on the efficacy of
      new therapies and into prognostic stratification for chronic heart failure
      patients. Firm conclusions on the usefulness of the test in clinical practice are
      still lacking. The aim of this study was to investigate (1) the correlation
      between walk test performance and standard indices of cardiac function and
      exercise capacity, and (2) the prognostic value of the walk test with respect to
      peak VO2 and NYHA class. METHODS AND RESULTS: Three hundred and fifteen chronic
      heart failure patients (age: 53+/-9 years, NYHA class: II (182), III (133))
      underwent a functional evaluation and a 6-min walk test. Of these, 270 were
      followed-up for a minimum of 6 months (mean 387+/-177 days). Walked distance was
      396+/-92 m. There was no significant correlation between distance walked and
      central haemodynamic data. Functional capacity, as measured by ergometry,
      correlated moderately with distance walked (duration: r=0.48, peak VO2: r=0.59,
      anaerobic threshold: r=0.54; all P<0.001). During follow-up, 46 patients died
      from cardiovascular causes and 12 were urgently transplanted. Either of these
      events were considered end points of the study. Survival analysis was performed
      from a continuous walk test and peak VO2 measurements or after categorization of
      (a) quartile segmentation, (b) cut-off points from the literature and (c)
      thresholds from receiver operating characteristic curves. At univariate survival
      analysis (Cox regression), the association of the walk test with survival was of
      significance (P=0.03, continuous variable), or borderline significance (0.05< or
      =P< or =0.1, after categorization). Peak VO2 was always significant, independent
      of the scale used (0.005< or =P< or =0.03). The strongest association was found
      for NYHA class (P<0.001), which showed the highest sensitivity and specificity
      for the prediction of the event (0.64 and 0.65, respectively). When walk test
      performance, continuous or categorized, was entered into a multivariate model
      with NYHA class or peak VO2, it lost any significant association with survival
      (P>0.76 in all models with NYHA class and P>0.27 in all models with peak VO2).
      CONCLUSION: In moderate-to-severe chronic heart failure patients, the 6-min walk
      test is not related to cardiac function and only moderately related to exercise
      capacity. Walking performance does not provide prognostic information which can
      complement or substitute for that provided by peak VO2 or NYHA class. Hence the
      test is of limited usefulness as a decisional indicator in clinical practice.

PMID- 11237545
TI  - Comparison of provocative tests for unexplained syncope: isoprenaline and
      glyceryl trinitrate for diagnosing vasovagal syncope.
AB  - AIMS: To compare the sensitivity, specificity and adverse event profile of
      glyceryl trinitrate head-up tilt with isoprenaline head-up tilt in the diagnosis
      of vasovagal syncope in patients with unexplained syncope and healthy controls.
      METHODS AND RESULTS: Forty-eight patients with unexplained syncope and negative
      passive head-up tilt at 70 degrees for 40 min, and 14 healthy controls underwent
      glyceryl trinitrate head-up tilt and isoprenaline head-up tilt (maximum dose 5
      microg x min(-1)) one week apart in random order. Outcome measures were
      production of symptoms (syncope, pre-syncope) with development of hypotension. In
      those with negative passive head-up tilt, the sensitivity of glyceryl trinitrate
      for diagnosing vasovagal syncope was 48% and the specificity was 71%. Glyceryl
      trinitrate was well tolerated. Isoprenaline sensitivity was 21% with specificity
      64%. Side-effects prevented completion of the test in 68%. Commonest adverse
      events were the development of hypertension or tachycardia and intolerable
      flushing or nausea. CONCLUSIONS: Glyceryl trinitrate head-up tilt is as effective
      as isoprenaline head-up tilt as a provocative agent for vasovagal syncope and has
      a lower incidence of adverse events.

PMID- 11237546
TI  - Does early repolarization in the athlete have analogies with the Brugada
      syndrome?
AB  - AIMS: To re-examine the prevalence and presentation of early repolarization in
      athletes and to compare it with electrocardiographic abnormalities observed in
      patients with the Brugada syndrome. METHODS: Electrocardiograms of 155 male
      athletes and 50 sedentary controls were studied. Early repolarization was
      considered present if at least two adjacent precordial leads showed elevation of
      the ST segment > or =1 mm. Amplitude and morphology of ST elevation, the leads
      where it was present and the lead in which it showed its maximum value were
      analysed together with QRS duration, the presence of right ventricular activation
      delay, QT and QTc duration. Data were compared with those obtained by
      electrocardiograms of 23 patients with the Brugada syndrome. RESULTS: Early
      repolarization was found in 139 athletes (89%) and 18 controls (36%, P< or
      =0.025), being limited to right precordial leads in 42 (30%) athletes and 13
      (72%) controls (P< or =0.001). Only 12 (8.6%) athletes and one control (5.5%)
      with early repolarization had an ST elevation 'convex toward the top' in right
      precordial leads, similar to that seen in the Brugada syndrome. In athletes the
      maximum ST elevation was greater (2.3+/-0.6 mm) than in the controls (1.2+/-0.8
      mm; P< or =0.004) but significantly lower than in patients with the Brugada
      syndrome (4.4+/-0.7 mm; P< or =0.0001). Patients with the Brugada syndrome also
      had a greater QRS duration (0.11+/-0.02 s) than athletes (0.090+/-0.011 s; P< or
      =0.0001) with early repolarization. CONCLUSIONS: Early repolarization is almost
      always the rule in athletes but it is also frequent in sedentary males. Tracings
      somewhat simulating the Brugada syndrome were observed in only 8% of athletes
      without a history of syncope or familial sudden death. Significant differences
      exist between athletes with early repolarization and patients with the Brugada
      syndrome as regards the amplitude of ST elevation and QRS duration.

PMID- 11237547
TI  - Cardioversion of atrial fibrillation or flutter: a 'stunning' problem.

PMID- 11237548
TI  - Cardiac nomenclature.

PMID- 11237552
TI  - Alterations in CD30(+) T cells in monoclonal gammopathy of undetermined
      significance.
AB  - Monoclonal gammopathy of unknown significance (MGUS) is a monoclonal B cell
      expansion characterized by high levels of circulating monoclonal antibody that
      affects 3% of individuals over the age of 70. Although this is considered benign,
      a high percentage of MGUS patients develop a debilitating peripheral autoimmune
      neuropathy and have a significantly increased risk for progression to multiple
      myeloma. Here we show that the relative numbers of the CD30(+) T cell subset and
      levels of CD30 expression are elevated in activated lymphocytes from normal aged
      individuals (> or =60 years) and in MGUS patients, when compared to younger
      controls. PBL from MGUS patients and age-matched controls produced comparable
      levels of IL-6 when activated with anti-CD3 plus IL-2, and costimulation with a
      soluble form of CD30 ligand (sCD30L/CD8alpha) augmented anti-CD3 inducible IL-6
      production similarly in both groups. However, MGUS PBL also produced measurable
      IL-6 when activated with sCD30L/CD8alpha alone. This capability was associated
      with the unique presence of CD30(+) T cells in the peripheral blood of MGUS
      patients. Furthermore, a higher percentage of activated MGUS T cells express CD30
      when activated by incubation with idiotype-expressing autologous serum (68 +/-
      13) than those activated by anti-CD3 plus IL-2 (43 +/- 7). These results indicate
      that quantitative alterations in CD30(+) T cells accompany aging and MGUS and
      that these cells may contribute to the chronic activation of B cells though the
      production of IL-6.

PMID- 11237553
TI  - Differential kinetics of intracellular caspase-1-like and caspase-3-like enzyme
      activity in human alloreactive CD4(+) and CD8(+) T cells undergoing apoptosis.
AB  - The ICE-like families of serine proteases (caspases) have integral roles in
      apoptosis. These studies were performed to further understand the role of two
      critical caspases in relation to apoptotic regulation of the alloimmune response.
      A novel three-color cytofluorographic technique was utilized for measuring
      intracellular (in situ) caspase-1-like and caspase-3-like enzyme activity in
      responding CD4(+) and CD8(+) T cells over several time points of human mixed
      lymphocyte reactions (MLR). We found that activity levels of caspase 3 in both
      CD4(+) and CD8(+) responder cells began rising at day 10 of the MLR and peaked at
      day 14. By comparison, caspase 1 demonstrated the highest activity at day 7 in
      both cell subpopulations. These results coincided with the appearance of
      apoptotic cells among the alloreactive cells in the MLR. These findings
      demonstrate that intracellular caspase-1- and -3-like enzyme activity increases
      in both CD4(+) and CD8(+) alloreactive T cells as the primary response to
      allostimulatory cells progresses. While the kinetic profiles for these enzymes
      differed, both had a temporal association with the appearance of apoptosis in the
      MLR-generated cells. In all cases, the highest enzyme activity and presence of
      apoptosis was seen subsequent to the peak proliferative period. These results
      support the concept that changes in the rate and amount of apoptosis in
      alloreactive T cells is one mechanism by which the response to alloantigens is
      attenuated (i.e., tolerance) or sustained.

PMID- 11237554
TI  - Immunologic reconstitution following bone marrow transplantation for X-linked
      hyper IgM syndrome.
AB  - X-linked hyper IgM syndrome (XHIM), caused by mutations of the CD40 ligand
      (CD40L) gene, is characterized by recurrent bacterial and opportunistic
      infections, an increased incidence of autoimmunity and malignancies, and
      immunodeficiency due to abnormal T/B cell interaction. Because of poor long-term
      prognosis, bone marrow transplantation (BMT) has been proposed as an alternative
      treatment. An 8-month-old boy with XHIM and a splice site mutation of CD40L
      underwent BMT using a fully matched sibling donor. Markers of engraftment and
      immunologic reconstitution were measured serially. After BMT, activated T cells
      expressed functional CD40L, and genomic DNA obtained from circulating white cells
      contained predominantly wild-type CD40L sequences. Serum immunoglobulin levels
      including IgE and antibody responses to recall antigens normalized, and
      immunization with the T-cell-dependent neoantigen, bacteriophage &phi;X174,
      demonstrated amplification of the response and isotope switching. BMT provides a
      permanent cure for XHIM if a fully matched sibling donor is available and the
      procedure is performed before complications have occurred.

PMID- 11237555
TI  - Humanized antibody to human interleukin-6 receptor inhibits the development of
      collagen arthritis in cynomolgus monkeys.
AB  - In the present study, we demonstrated the anti-arthritic effect of humanized anti
      human IL-6 receptor (IL-6R) antibody, MRA, in cynomolgus monkey. MRA can react
      with monkey IL-6R and block signal transduction of IL-6. Collagen-induced
      arthritis (CIA) was induced by twice immunizing with bovine type II collagen
      (CII) emulsified with complete adjuvant. MRA was intravenously injected once a
      week, from the day of the first collagen immunization, for 13 weeks. The symptoms
      of arthritis were evaluated using a visual scoring system and radiography.
      Inflammatory parameters (C-reactive protein (CRP), fibrinogen, and erythrocyte
      sedimentation rate (ESR) and concentrations of anti-CII antibody, anti-MRA
      antibody, and MRA were monitored regularly. At the end of the study, histological
      evaluation was carried out. MRA, at a dose of 10 mg/kg, gave rise to
      statistically significant suppression. The elevation of serum CRP and fibrinogen
      levels and ESR were also inhibited. Furthermore, radiographic and histological
      examination showed that MRA treatment suppressed joint destruction. Our results
      demonstrate that IL-6 plays an important role in monkey CIA and that MRA may be
      an attractive agent for the treatment of rheumatoid arthritis.

PMID- 11237556
TI  - Purified recombinant A. fumigatus allergens induce different responses in mice.
AB  - Aspergillus fumigatus an opportunistic fungus is associated with a number of
      diseases in humans. Allergy resulting from exposure to the A. fumigatus allergens
      has been recognized frequently. The damage caused by the disease is very striking
      in patients with atopy and those with cystic fibrosis. Avoidance to exposure is
      not feasible because A. fumigatus spores are ubiquitously distributed in the
      environment. Hence, immunotherapeutic regimens in severe forms of A. fumigatus
      allergy may have a high potential. However, before such forms of therapy can be
      envisaged, it is essential to understand the immunopathogenesis. In the present
      study, we investigated the role of purified A. fumigatus allergens in the
      development of allergic asthma in mice. We have used four major recombinant A.
      fumigatus allergens in the murine model. Mice exposed to Asp f 1, f 3, and f 4
      showed inflammatory changes in the lungs and airway hyperreactivity. The immune
      responses, including elevated serum IgE, enhanced eosinophils, recruitment in the
      peripheral blood and lungs, and expression of regulatory cytokines, are
      characteristic of a Th2 response. Asp f 6 demonstrated only a reduced response in
      these animals. The results suggest that the pathology induced by crude A.
      fumigatus extract results from the cumulative effects of the allergens and the
      individual responses varied considerably with different purified antigens.

PMID- 11237557
TI  - Prostaglandin J(2) inhibition of mesangial cell iNOS expression.
AB  - Mesangial cells from MRL/lpr mice, a model of lupus, overproduce nitric oxide
      (NO) compared to controls. J series prostaglandins (PG) and thiazolidinediones
      block LPS stimulation of NO production via the activation of peroxisome
      proliferator-activator receptor-gamma (PPAR-gamma) in macrophages but utilize an
      alternative mechanism in microglial cells. We investigated the mechanism by which
      PGJ(2) inhibits NO production in LPS/IFN-gamma-stimulated MRL/lpr mesangial
      cells. Our results demonstrated that LPS/IFN-gamma addition to MRL/lpr mesangial
      cells stimulated iNOS activation, expression of p-38 kinase and p44/42 MAPK, and
      NF-kappaB translocation to the nucleus. Both pioglitazone, a specific PPAR-gamma
      agonist, and PGJ(2) blocked NO production, iNOS protein expression, and iNOS mRNA
      transcription. PGJ(2) failed to inhibit nuclear NF-kappaB translocation or p44/42
      MAPK or p-38 kinase induction in stimulated mesangial cells. These data suggest
      that PGJ(2) blocks iNOS expression and subsequent NO production in mesangial
      cells via a PPAR-gamma-mediated mechanism either by interfering with NF-kappaB
      transcriptional activity or by an NF-kappaB-independent mechanism.

PMID- 11237558
TI  - The tumor recall response of antitumor immunity primed by a live, recombinant
      Listeria monocytogenes vaccine comprises multiple effector mechanisms.
AB  - Listeria monocytogenes, a facultative intracellular bacterium, can induce a
      potent antitumor immune response if engineered to express a model tumor antigen
      also expressed by the tumor cells. The effectiveness of this approach is
      dependent on L. monocytogenes-induced tumor-specific CD4(+) and CD8(+) T-cells.
      CD8(+) T-cells may mediate tumor eradication largely through direct CTL activity,
      but the role of CD4(+) T-cells and other cells of the immune system is less
      clear. Here we investigate their role and the role of the cytokines they produce
      in the ability of L. monocytogenes-induced antitumor immunity to protect against
      tumor challenge. Our results suggest that a complex cytokine response, involving
      type 2 as well as type 1 cytokines, is responsible for the ability of Lm-NP
      immunized mice to resist tumor challenge, potentially mediating tumor cell
      killing through multiple effector pathways.

PMID- 11237559
TI  - Human gammadelta T cells express a higher TCR/CD3 complex density than alphabeta
      T cells.
AB  - The aim of our study was to compare CD3 expression on gammadelta T cells and
      alphabeta T cells in human patients. The antigen density of TCR and CD3 on both
      subsets was assessed by a quantitative method in eight patients. In parallel, we
      developed and validated a reliable direct tricolor staining protocol that we
      tested on samples from hospitalized and healthy individuals (n = 60). Our results
      demonstrate that human gammadelta T cells constitutively express approximately
      twofold more of the TCR/CD3 complex than alphabeta T cells. We suggest that this
      enhanced expression of the TCR/CD3 complex could contribute to the higher
      reactivity of gammadelta T cells compared to alphabeta T cells. These clinical
      laboratory results confirm the fundamental data described elsewhere. gammadelta T
      cells deserve further clinical investigations to understand their precise role in
      human immunity.

PMID- 11237560
TI  - Spontaneous inflammatory disease in HLA-B27 transgenic mice does not require
      transporter of antigenic peptides.
AB  - HLA-B27 is strongly linked with a group of human diseases called
      spondyloarthropathies. Even though HLA-B27 as an MHC class I molecule would be
      expected to present endogenously processed peptides such as cytosolic or viral
      proteins, many of the B27-linked diseases begin after an infection with an
      enterobacteria, an exogenous antigen. In our previous studies, we have described
      development of spontaneous inflammatory disease in HLA-B27 transgenic mice
      expressing beta(2)m free heavy chains on the cell surface. In order to address
      the role of endogenous versus exogenous antigens and a role for Tap genes in the
      development of spontaneous diseases, mice lacking Tap-1 (knockout) were mated to
      HLA-B27/human beta(2)m transgenic mice. B27(+)/human beta(2)m(+) double
      transgenic mice (without mouse beta(2)m) lacking the Tap-1 gene developed
      spontaneous inflammatory disease similar to wild-type Tap-1 gene-expressing
      counterparts. Our data demonstrate that peptide transporters (Tap) were not
      involved in the development of spontaneous inflammatory disease in B27(+)/human
      beta(2)m transgenic animals.

PMID- 11237561
TI  - Morphine modulation of the contact hypersensitivity response: characterization of
      immunological changes.
AB  - Previous investigations in our laboratory showed that systemic morphine
      administration 1 h prior to elicitation of the in vivo contact hypersensitivity
      (CHS) response produced a robust increase in inflammation at the site of antigen
      reexposure. The present study extended those findings by characterizing the
      effect of morphine on immunological processes important in the development of the
      CHS response. To induce contact hypersensitivity, the antigen 2,4
      dinitrofluorobenzene was applied to the pinnae of previously sensitized rats.
      Morphine administration produced an increase in inducible nitric oxide synthase
      mRNA and the proinflammatory cytokine interleukin-6, at the site of antigen
      reexposure. In contrast, morphine did not alter expression of the anti
      inflammatory cytokine interleukin-10. Morphine also produced an increase in the
      proliferation of lymphocytes from the peripheral (i.e., cervical) lymph nodes
      when assessed 72 h following challenge. These studies show that the morphine
      induced increase in the in vivo CHS response involves immunologically specific
      alterations.

PMID- 11237562
TI  - Tissue transglutaminase and endomysial antibodies-diagnostic markers of gluten
      sensitive enteropathy in dermatitis herpetiformis.
AB  - The association of Durhing's disease, commonly referred to as dermatitis
      herpetiformis (DH), with gluten-sensitive enteropathy (GSE) is supported by the
      presence of villous atrophy and endomysial antibodies (EMA). EMA are found to be
      a marker of GSE both in celiac disease (CD) and in DH. Since tissue
      transglutaminase (tTG) is believed to be the major autoantigen in GSE, the aim of
      our study was to determine the specificity and sensitivity of anti-tTG antibody
      ELISA compared to the EMA indirect immunofluorescence test. We studied 44 cases
      of DH, confirmed by the presence of IgA immune deposits in the dermal papillae,
      and 58 cases of CD conforming to the International Criteria of Diagnosing CD. The
      control group comprised 161 sera from patients with vesiculobullous disorders
      other than DH and 106 sera from normal healthy blood donors. Anti-tTG antibodies
      were detected in 36 of 44 DH (79%) and in 32 of 58 CD (55%) patients. EMA were
      positive in 33 of 44 DH (74%) and in 36 of 58 CD (62%) patients. Both the EMA and
      the antibodies to tTG were present in the majority of patients with DH and CD
      when they were on a normal gluten-containing diet and were absent when on a
      gluten-free diet for an extended period of time. There were, however, small
      discrepancies in positivity and negativity in tTG antibody-positive and EMA
      negative patients and vice versa. There seems to be a correlation between the EMA
      titers and the anti-tTG antibody levels. This study confirms the high specificity
      and sensitivity of anti-tTG antibody ELISA for GSE and its strong correlation
      with EMA both in CD and in DH. The results of anti-tTG antibody and EMA assays
      were comparable; however, in DH, tTG was somewhat more sensitive than the EMA
      test. For screening of DH, it is advisable to perform both EMA and anti-tTG
      antibody tests.

PMID- 11237563
TI  - Re: Duffy phenotype does not influence the clinical severity of sickle cell
      disease.

PMID- 11237565
TI  - A prediction on the sex ratios of piglets.

PMID- 11237566
TI  - Control of 92 kDa collagenase secretion in mammalian cells by modulation of AP-1
      activity: an experimentally based theoretical study.
AB  - Collagenolytic enzymes control cell migration through connective tissues. They
      appear to be of crucial importance for angiogenesis, tumor metastasis or wound
      repair. A well-documented stimulation pathway of collagenase secretion, either by
      natural (cytokines) or synthetic (phorbol esters) molecules, acts through
      activation of the proto-oncogene activating protein 1 (AP-1). Interestingly, this
      nuclear factor enhances its own synthesis. It also modulates the activity of
      different genes, including the one coding for 92 kDa gelatinase. We developed a
      mathematical model to describe this pathway. It led us to conjecture the
      existence of an hysteresis cycle for PMA-stimulated collagenase secretion, which
      was experimentally demonstrated later in MDBK cells in culture. We also modified
      our model to simulate the behavior of tumoral cells expressing AP-1. In this
      case, the system becomes highly unstable and, once stimulated, cannot be brought
      back to rest. This approach paved the way for the understanding and the control
      of mammalian cell processes, connective tissue maintenance or metastasis
      dissemination.

PMID- 11237567
TI  - Re-examination of the "3/4-law" of metabolism.
AB  - We examine the scaling law B is proportional to M(alpha)which connects organismal
      resting metabolic rate B with organismal mass M, where alpha is commonly held to
      be 3/4. Since simple dimensional analysis suggests alpha = 2/3, we consider this
      to be a null hypothesis testable by empirical studies. We re-analyse data sets
      for mammals and birds compiled by Heusner, Bennett and Harvey, Bartels,
      Hemmingsen, Brody, and Kleiber, and find little evidence for rejecting alpha =
      2/3 in favor of alpha = 3/4. For mammals, we find a possible breakdown in scaling
      for larger masses reflected in a systematic increase in alpha. We also review
      theoretical justifications of alpha = 3/4 based on dimensional analysis, nutrient
      supply networks, and four-dimensional biology. We find that present theories for
      alpha = 3/4 require assumptions that render them unconvincing for rejecting the
      null hypothesis that alpha = 2/3.

PMID- 11237568
TI  - The Goodwin model: simulating the effect of light pulses on the circadian
      sporulation rhythm of Neurospora crassa.
AB  - The Goodwin oscillator is a minimal model that describes the oscillatory negative
      feedback regulation of a translated protein which inhibits its own transcription.
      Now, over 30 years later this scheme provides a basic description of the central
      components in the circadian oscillators of Neurospora, Drosophila, and mammals.
      We showed previously that Neurospora's resetting behavior by pulses of
      temperature, cycloheximide or heat shock can be simulated by this model, in which
      degradation processes play an important role for determining the clock's period
      and its temperature-compensation. Another important environmental factor for the
      synchronization is light. In this work, we show that on the basis of a light
      induced transcription of the frequency (frq) gene phase response curves of light
      pulses as well as the influence of the light pulse length on phase shifts can be
      described by the Goodwin oscillator. A relaxation variant of the model predicts
      that directly after a light pulse inhibition in frq -transcription occurs, even
      when the inhibiting factor Z (FRQ) has not reached inhibitory concentrations.
      This has so far not been experimentally investigated for frq transcription, but
      it complies with a current model of light-induced transcription of other genes by
      a phosphorylated white-collar complex. During long light pulses, the relaxational
      model predicts that the sporulation rhythm is arrested in a steady state of high
      frq -mRNA levels. However, experimental results indicate the possibility of
      oscillations around this steady state and more in favor of the results by the
      original Goodwin model. In order to explain the resetting behavior by two light
      pulses, a biphasic first-order kinetics recovery period of the blue light
      receptor or of the light signal transduction pathway has to be assumed.

PMID- 11237569
TI  - The evolutionary dynamics of grammar acquisition.
AB  - Grammar is the computational system of language. It is a set of rules that
      specifies how to construct sentences out of words. Grammar is the basis of the
      unlimited expressibility of human language. Children acquire the grammar of their
      native language without formal education simply by hearing a number of sample
      sentences. Children could not solve this learning task if they did not have some
      pre-formed expectations. In other words, children have to evaluate the sample
      sentences and choose one grammar out of a limited set of candidate grammars. The
      restricted search space and the mechanism which allows to evaluate the sample
      sentences is called universal grammar. Universal grammar cannot be learned; it
      must be in place when the learning process starts. In this paper, we design a
      mathematical theory that places the problem of language acquisition into an
      evolutionary context. We formulate equations for the population dynamics of
      communication and grammar learning. We ask how accurate children have to learn
      the grammar of their parents' language for a population of individuals to evolve
      and maintain a coherent grammatical system. It turns out that there is a maximum
      error tolerance for which a predominant grammar is stable. We calculate the
      maximum size of the search space that is compatible with coherent communication
      in a population. Thus, we specify the conditions for the evolution of universal
      grammar.

PMID- 11237570
TI  - Balance between four types of synaptic input for the integrate-and-fire model.
AB  - We consider the integrate-and-fire model with AMPA, NMDA, GABA(A)and
      GABA(B)synaptic inputs, with model parameters based upon experimental data. An
      analytical approach is presented to determine when a post-synaptic balance
      between excitation and inhibition can be achieved. Secondly, we compare the model
      behaviour subject to these four types of input, with its behaviour subject to
      conventional point process inputs. We conclude that point processes are not a
      good approximation, even away from exact presynaptic balance. Thirdly, numerical
      simulations are presented which demonstrate that we can treat NMDA and GABA(B)as
      DC currents. Finally, we conclude that a balanced input is plausible neither pre
      synaptically nor post-synaptically for the model and parameters we employed.

PMID- 11237571
TI  - Inference of past population expansion from the timing of coalescence events in a
      gene genealogy.
AB  - We investigate the expected coalescent in populations growing exponentially. The
      distribution of expected times to coalescence events may show a linear
      relationship with a number of ancestral lineages, when the latter is subjected to
      the "epidemic transformation". However, in a number of viral populations, upward
      curves are created when the epidemically transformed number of ancestral lineages
      is plotted against time. We consider possible causes of such upward curves. These
      include the possibility that a curved line is created through a transformation
      failure due to a sample size that is too large. We suggest a new formula for
      predicting such failure. The second cause is a population size increasing at an
      accelerating rate. However, the combination of recent coalescent events and an
      upward curve is created by an accelerating population increase only under
      restricted conditions. Specifically, such a pattern is expected only when, were
      population growth not to have accelerated, the transformation would have failed
      anyway. The third cause of nonlinearity arises in the estimated coalescent, as
      distinct from the real coalescent, if the mutation rate is small. However,
      coalescence times estimated from data typically give a straight line following
      epidemic transformation, but the rate of exponential increase, or r value, will
      be underestimated.

PMID- 11237572
TI  - Heterogeneity stabilizes reciprocal altruism interactions.
AB  - In considering the phenomena of reciprocal altruism few would dispute that there
      are differences in individual quality-in particular, that for some individuals,
      at least on occasion, the cost of doing favors will exceed the potential of
      future benefits. That is, at any given time, a typical population is
      heterogeneous with respect to the affordability of reciprocal altruism. However,
      methodological limitations of the traditional analytical framework-Single Type
      (symmetric) Evolutionary Game Theory-have restricted previous analytical efforts
      to addressing populations idealized in terms of their averages. Here we use the
      methods of Multitype Evolutionary Game Theory to analyse the role of individual
      differences in direct reciprocity interactions. Multitype analysis shows that non
      idealized populations possess an ESS profile wherein individuals who cannot
      afford reciprocity (low-quality) defect, while individuals who derive net
      benefits from reciprocity (high-quality) cooperate. Furthermore, this cooperation
      is implemented via unmodified tit-for-tat (TfT) strategy. Hence, our results may
      help resolve a long-standing problem concerning the evolutionary stability of TfT
      in direct reciprocal altruism. Finally, this difference between idealized and
      real populations is not restricted to direct reciprocal cooperation. Previously
      (Lotem et al., 1999) we have demonstrated evolutionarily stable indirect
      reciprocal cooperation among high-quality individuals in heterogeneous
      populations.

PMID- 11237573
TI  - Hypothesis: gonadal hormones act as confounders in epidemiological studies of the
      associations between some behavioural risk factors and some pathological
      conditions.
AB  - There are grounds for suspecting that, to varying degrees, smoking, alcohol
      consumption, oral contraceptive use, vasectomy and induced abortion are markers
      for high steroid hormone levels. So in epidemiological studies, false inferences
      may be drawn that these markers (treated as risk factors) have causal or
      exacerbating effects on diseases which are truly partially caused by high levels
      of hormones (e.g. probably prostatic cancer and breast cancer). Analogously, such
      studies of conditions which are truly partially caused by low levels of hormones
      (e.g. bone fractures, poor sperm quality, and perhaps testicular cancer and
      rheumatoid arthritis) may yield spurious suggestions of an ameliorative effect.
      The results of epidemiological studies of the above five "risk factors" for the
      above six pathologies are-in many cases-in striking disarray. I suggest that this
      is, at least partially, because of this form of confounding. The point may be
      tested by contrasting the hormone levels of people who self-select for smoking,
      vasectomy, etc., at the time that self-selection is made with those of
      appropriately selected control subjects.

PMID- 11237574
TI  - A dynamical systems model to simulate the perturbation kinetics of gene
      expression by antisense oligonucleotides.
AB  - Antisense oligonucleotides owe their efficacy to an ability to induce RNase H
      dependent suppression of RNA translation, for sufficient time to allow
      physiological proteolysis. The magnitude and time delay preceding the protein
      nadir concentration determine the extent and timing of maximum antisense
      oligonucleotide activity. Antisense oligonucleotide degradation underlies
      reversal of RNA downregulation. The kinetics of protein downregulation is
      therefore determined by the complex interaction of both ligand chemistry
      (nuclease stability, affinity and RNase H activation), and gene expression
      kinetics. Optimization of antisense oligonucleotide efficacy and experimental
      design requires understanding of these interactions. The kinetics of protein and
      RNA downregulation have therefore been simulated by analysing a two-compartment
      kinetic model incorporating RNase H-dependent transcript degradation. The system
      of nonlinear differential equations describing this model was solved numerically
      using Runge-Kutte integration. The timecourse solutions corresponding to the four
      state variables (RNA, protein, antisense/RNA heteroduplex and antisense
      oligonucleotide), were determined simultaneously. This allowed systematic in
      silico examination of the consequences of altering variables such as
      oligonucleotide concentration, affinity, and stability, or the scheduling of
      multiple transfections on RNA and protein perturbations. By providing a tool for
      examining antisense oligonucleotide action theoretically, this heuristic model
      should facilitate both the rational design and interpretation of antisense
      experiments.

PMID- 11237575
TI  - Resonance in periodic chemotherapy: a case study of acute myelogenous leukemia.
AB  - The effects of periodic chemotherapy administration are evaluated within the
      context of a G(0)model of the cell cycle. Parameters are estimated for normal
      bone marrow cells and malignant cells in acute myelogenous leukemia (AML). This
      model explicitly includes the resting G(0)phase and the feedback mechanism that
      recruits the cells back into the cell cycle. Periodic chemotherapy administration
      can induce resonance within our model under high cell kill rate where the average
      cell cycle times may change during the course of treatment, and therapeutic
      benefits from these resonances cannot be solely based on cell cycle times in
      untreated tissue. The depletion rate under chemotherapy and the regrowth rate may
      differ between the cell populations, and our analysis suggests that this favors
      the tumour cells. We were able to distinguish between the effects of cycle-non
      specific, S -phase-specific and M -phase-specific drugs, and found that these can
      show differences in sharpness and location of the resonance phenomenon. We
      conclude that resonance chemotherapy (chronotherapy) is unlikely to be
      efficacious in the treatment of AML.

PMID- 11237589
TI  - NMR identification of the Tom20 binding segment in mitochondrial presequences.
AB  - Many mitochondrial proteins are synthesized in the cytosol as precursors with N
      terminal presequences, and are imported into mitochondria with the aid of
      translocator protein complexes containing presequence-binding proteins. Tom20, a
      receptor protein which functions in an early step of the mitochondrial protein
      import, recognizes presequences with divergent amino acid sequences. Here, we
      report the identification of the segments involved in binding to Tom20 in
      mitochondrial presequences. We monitored the chemical shift perturbation of the
      NMR signals of five different 15N-labeled presequence peptides by the addition of
      the cytosolic receptor domain of rat or yeast Tom20. The perturbed segments
      occupy different positions, either near the N terminus or at the C terminus, in
      the presequences. Spin label experiments revealed that this is not due to
      different orientations of the presequence peptides bound to Tom20. The results
      presented here will offer a starting point to perform detailed analyses of Tom20
      binding elements by systematic amino acid replacements.

PMID- 11237591
TI  - The in vivo conformation of the plastid DNA of Toxoplasma gondii: implications
      for replication.
AB  - The Phylum Apicomplexa comprises thousands of obligate intracellular parasites,
      some of which cause serious disease in man and other animals. Though not
      photosynthetic, some of them, including the malaria parasites (Plasmodium spp.)
      and the causative organism of Toxoplasmosis, Toxoplasma gondii, possess a remnant
      plastid partially determined by a highly derived residual genome encoded in 35 kb
      DNA. The genetic maps of the plastid genomes of these two organisms are extremely
      similar in nucleotide sequence, gene function and gene order. However, a study
      using pulsed field gel electrophoresis and electron microscopy has shown that in
      contrast to the malarial version, only a minority of the plastid DNA of
      Toxoplasma occurs as circular 35 kb molecules. The majority consists of a precise
      oligomeric series of linear tandem arrays of the genome, each oligomer
      terminating at the same site in the genetic map, i.e. in the centre of a large
      inverted repeat (IR) which encodes duplicated tRNA and rRNA genes. This overall
      topology strongly suggests that replication occurs by a rolling circle mechanism
      initiating at the centre of the IR, which is also the site at which the linear
      tails of the rolling circles are processed to yield the oligomers. A model is
      proposed which accounts for the quantitative structure of the molecular
      population. It is relevant that a somewhat similar structure has been reported
      for at least three land plant chloroplast genomes.

PMID- 11237590
TI  - Dissection of the promoter region of the inositol 1,4,5-trisphosphate receptor
      gene, itr-1, in C. elegans: a molecular basis for cell-specific expression of
      IP3R isoforms.
AB  - Inositol 1,4,5-trisphosphate receptors in Caenorhabditis elegans are encoded by a
      single gene, itr-1. This provides a powerful system in which to dissect the
      mechanisms that control the tissue-specific expression of molecules that
      determine the specificity of calcium signalling. We first identified the
      Caenorhabditis briggsae orthologue of itr-1, Cbitr-1. Comparison of the two itr-1
      genes revealed that the chromosomal organisation, gene structure and predicted
      cDNA and protein sequences were all conserved. The conserved gene structure
      supports the hypothesis that the itr-1 gene has three promoters, each of which
      gives rise to an alternative mRNA and hence unique protein. To test this and to
      identify the roles of the three putative promoters (pA, pB and pC) in regulating
      itr-1 expression we fused each promoter to the green fluorescent protein gene and
      identified their expression patterns. Introduction of these transgenes into C.
      elegans identified unique and defined patterns of green fluorescent protein
      expression directed by each promoter: pA directs expression in the pharyngeal
      terminal bulb, the rectal epithelial cells and vulva; pB directs expression in
      the motor neurone PDA, the amphid socket cells and the spermatheca; pC directs
      expression in the spermathecal valve, uterine sheath cells, pharyngeal isthmus
      and intestine. Thus tissue-specific expression of itr-1 variants is directed by
      three promoters and this results in adjacent cells in the same tissue containing
      different inositol trisphosphate receptor isoforms. Within pA, four short regions
      (pA-A to pA-D) of sequence conservation between C. elegans and C. briggsae were
      identified. Deletion analysis demonstrated that the region containing pA-C is
      required for expression in the terminal bulb and rectal epithelial cells and the
      region containing pA-D is required for expression in the vulva. pA-C includes
      sequences similar to the binding sites for transcription factors that have been
      demonstrated to be important in pharyngeal development and gene expression.

PMID- 11237592
TI  - Alkylating agent and chromatin structure determine sequence context-dependent
      formation of alkylpurines.
AB  - We determined the adduct maps of S(N)1 and S(N)2 alkylating agents in cultured
      human cells (in vivo) and in vitro to probe DNA-protein interactions along
      sequences of the promoter and exon 1 of the Fragile-X mental retardation 1 (FMR1)
      gene. Using ligation-mediated polymerase chain reaction (LMPCR), we compared the
      piperidine-sensitive alkylpurines sites generated by treating cultured cells (in
      vivo) and naked DNA (in vitro) with S(N)1 (N-methyl-N-nitrosourea, N
      nitroso(acetoxymethyl)methylamine and 1-methyl-3-nitro-1-nitrosoguanidine) and
      S(N)2 alkylating agents (dimethyl sulfate (DMS), methane sulfonic acid methyl
      ester, iodo methane, diethyl sulfate, methane sulfonic acid ethyl ester and iodo
      ethane). The FMR1 promoter has four sites where DNA-protein interactions are
      observed. In these regions, the S(N)1 methylating agent reactions produced only
      hypo-reactive sites. In contrast, iodoalkane S(N)2 alkylating agents (MeI and
      EtI) reactions generated only hyper-reactive sites. Although there are hyper
      reactive sites for the other S(N)2 reagents, the hyper-reactive site at +14 on
      the FMR1 map is more pronounced for the sulfate and sulfonate-derived alkylating
      agents than for the iodoalkanes. However, DMS modification in the presence of
      methyl sulfone, a compound that does not alkylate DNA, eliminates the hyper
      reactive site observed at +14. This suggests that the electron-rich oxygen atoms
      of the sulfate and sulfonate-derived S(N)2 alkylating agent structure position
      the alkylating moiety to the neighboring N-7-guanine position to favor alkyl
      transfer to the guanine. Using KMnO(4) to probe for single-strand DNA, an
      unpaired cytosine base was detected at the 5'-side of the hyper- reactive guanine
      base at position +14, consistent with the formation of a local DNA single-strand
      bulge. In conclusion, we show that the sequence context-dependent formation of
      alkylpurines is determined by the chemical nature of the alkylating agent, the
      DNA sequence context, chromatin structure, and the presence of other non-reactive
      molecules that can inhibit alkylation.

PMID- 11237593
TI  - Interaction of tyrosine 65 of RecA protein with the first and second DNA strands.
AB  - We investigated the structure of the active RecA-DNA complex by analyzing the
      environment of tyrosine residue 65, which is on the DNA-binding surface of the
      protein. We prepared a modified RecA protein in which the tyrosine residue was
      replaced by tryptophan, a natural fluorescent reporter, and measured the change
      in its fluorescence upon binding of DNA and cofactor. The fluorescence of the
      inserted tryptophan 65 (Trp65) was centered at 345 nm, indicating a partly
      exposed residue. Binding cofactor, adenosine 5'-O-3-thiotriphosphate (ATPgammaS),
      alone at a low salt concentration did not change the fluorescence of Trp65,
      confirming that the residue is not close to the nucleotide. In contrast, the
      binding of single-stranded DNA quenched the fluorescence of Trp65 in both the
      presence and absence of ATPgammaS. Trp65 fluorescence was also quenched upon
      binding a second DNA strand. The fluorescence change depended upon the presence
      and absence of ATPgammaS, reflecting the difference in the DNA binding. These
      results indicate that residue 65 is close to both the first and second DNA
      strands. The degree of quenching depended upon the base composition of DNA,
      suggesting that the residue 65 interacts with the DNA bases. Binding of DNA with
      ATPgammaS as well as binding of ATPgammaS alone at high salt concentration
      shifted the fluorescence emission peak from 345 to 330 nm, indicating a change
      from a polar to a non-polar environment. Therefore, the environment change around
      residue 65 would also be linked to a change in conformation and thus the
      activation of the protein.

PMID- 11237594
TI  - Modulation of Sp1 activity by a cyclin A/CDK complex.
AB  - Transcription factors of the Sp1 family are targets of several regulatory
      pathways and can induce or inhibit gene expression. Here we show that Sp1 is
      associated with a histone 1 kinase activity. This activity is growth regulated
      and correlates with the expression of cyclin A. Co-immunoprecipitation
      experiments demonstrate, that Sp1 interacts with cyclin A and can be
      phosphorylated by a cyclin A associated kinase. The interaction is direct and
      requires the zinc-finger region of Sp1 and the amino-terminal domain of cyclin A.
      Over-expression of cyclin A enhances the expression of a reporter gene controlled
      by an Sp1 responsive promoter. Addition of olomoucine, a specific inhibitor of
      CDK2 and CDC2 activity on the other hand reduces the expression of the reporter.
      Electrophoretic mobility shift assays suggest that this is due to a reduction of
      the DNA-binding ability of Sp1 family members. Our results indicate that
      phosphorylation of Sp1 and other members of the family by a cyclin A/CDK complex
      may play a role in the growth and cell cycle regulation of its transcriptional
      activity.

PMID- 11237595
TI  - Interaction of the C-terminal domain of the E. coli RNA polymerase alpha subunit
      with the UP element: recognizing the backbone structure in the minor groove
      surface.
AB  - The C-terminal domain of the alpha-subunit of Escherichia coli RNA polymerase
      (alphaCTD) is responsible for transcriptional activation through interaction with
      both activator proteins and UP element DNA. Previously, we determined the
      solution structure of alphaCTD. Here, we investigated the interaction between
      alphaCTD and UP element DNA by NMR. DNA titration curves and intermolecular NOE
      measurements indicate that alphaCTD can bind to multiple sites on the UP element
      DNA. Unlike many transcription factors, alphaCTD does not have a strict base
      sequence requirement for binding. There is a good correlation between the
      strength of the interaction and the extent of intrinsic bending of the DNA
      oligomer estimated from the gel retardation assay. We propose that alphaCTD
      recognizes the backbone structure of DNA oligomers responsible for the intrinsic
      bending. Moreover, NMR studies and drug competition experiments indicated that
      alphaCTD interacts with the UP element on the minor groove side of the DNA. The C
      terminal end of helix-1, the N-terminal end of helix-4, and the loop between
      helices 3 and 4 are used for the interaction. Based on these observations, we
      propose a model for the UP element-alphaCTD complex.

PMID- 11237596
TI  - Conformation and rigidity of DNA microcircles containing waf1 response element
      for p53 regulatory protein.
AB  - The tumor-suppressor activity of p53 is closely related to its DNA-binding
      properties. It binds a number of DNA response-elements and it is likely that
      these share a common structural feature. Here, we present a new, general method
      to determine the absolute twist of flexible DNA promoter sequences based on
      direct imaging of the topology of microcircles containing the sequences. We have
      used magnetically driven dynamic force microscopy ("MacMode" AFM) to observe, in
      solution, the conformation of 168 base-pair DNA microcircles, each containing
      four equally spaced copies of the waf1/cip1/p21 p53 response-element. Analysis of
      the images showed that the microcircles are markedly puckered with a small excess
      of negatively writhed molecules. The average measured values of writhe are
      0.109+/-0.013 (for 60 positively writhed molecules) and -0.098+/-0.011 (for 65
      negatively writhed molecules). These values lead directly to a difference in
      linking number for the positively and negatively writhed molecules prior to
      ligation, from which we derive a twist mismatch of 178 degrees (overtwist). This
      is 44.5 degrees for each 42-mer precursor containing a single waf1/cip1/p21 p53
      response-element, in good agreement with the range of values deduced by indirect
      biochemical techniques. The two values of writhe may also be used to determine
      the ratio of the bending (B) to twisting (C) rigidity, yielding B/C=0.23. This is
      about one-third of the value for long, random-sequence DNA, suggesting that the
      waf1/cip1/p21 p53 response-element is extremely flexible, a result that is also
      consistent with indirect biochemical experiments. These results support the idea,
      proposed by us earlier, that torsional stress may play a role in the regulation
      of p53 binding through modulation of twist at the binding site.

PMID- 11237597
TI  - Crystal structure of the NADP(H)-dependent ketose reductase from Bemisia
      argentifolii at 2.3 A resolution.
AB  - Polyhydric alcohols are widely found in nature and can be accumulated to high
      concentrations as a protection against a variety of environmental stresses. It is
      only recently, however, that these molecules have been shown to be active in
      protection against heat stress, specifically in the use of sorbitol by the
      silverleaf whitefly, Bemisia argentifolii. We have determined the structure of
      the enzyme responsible for production of sorbitol in Bemisia argentifolii,
      NADP(H)-dependent ketose reductase (BaKR), to 2.3 A resolution. The structure was
      solved by multiwavelength anomalous diffraction (MAD) using the anomalous
      scattering from two zinc atoms bound in the structure, and was refined to an R
      factor of 21.9 % (R(free)=25.1 %). BaKR belongs to the medium-chain dehydrogenase
      family and its structure is the first for the sorbitol dehydrogenase branch of
      this family. The enzyme is tetrameric, with the monomer having a very similar
      fold to the alcohol dehydrogenases (ADHs). Although the structure determined is
      for the apo form, a phosphate ion in the active site marks the likely position
      for the adenyl phosphate of NADP(H). The catalytic zinc ion is tetrahedrally
      coordinated to Cys41, His66, Glu67 and a water molecule, in a modification of the
      zinc site usually found in ADHs. This modified zinc site seems likely to be a
      conserved feature of the sorbitol dehydrogenase sub-family. Comparisons with
      other members of the ADH family have also enabled us to model a ternary complex
      of the enzyme, and suggest how structural differences may influence coenzyme
      binding and substrate specificity in the reduction of fructose to sorbitol.

PMID- 11237598
TI  - Crystal structure and site-directed mutagenesis studies of N-carbamoyl-D-amino
      acid amidohydrolase from Agrobacterium radiobacter reveals a homotetramer and
      insight into a catalytic cleft.
AB  - The N-carbamoyl-D-amino-acid amidohydrolase (D-NCAase) is used on an industrial
      scale for the production of D-amino acids. The crystal structure of D-NCAase was
      solved by multiple isomorphous replacement with anomalous scattering using xenon
      and gold derivatives, and refined to 1.95 A resolution, to an R-factor of 18.6 %.
      The crystal structure shows a four-layer alpha/beta fold with two six-stranded
      beta sheets packed on either side by two alpha helices. One exterior layer faces
      the solvent, whereas the other one is buried and involved in the tight
      intersubunit contacts. A long C-terminal fragment extends from a monomer to a
      site near a dyad axis, and associates with another monomer to form a small and
      hydrophobic cavity, where a xenon atom can bind. Site-directed mutagenesis of
      His129, His144 and His215 revealed strict geometric requirements of these
      conserved residues to maintain a stable conformation of a putative catalytic
      cleft. A region located within this cleft involving Cys172, Glu47, and Lys127 is
      proposed for D-NCAase catalysis and is similar to the Cys-Asp-Lys site of N
      carbamoylsarcosine amidohydrolase. The homologous active-site framework of these
      enzymes with distinct structures suggests convergent evolution of a common
      catalytic mechanism.

PMID- 11237600
TI  - Solution structure and dynamics of an open beta-sheet, glycolytic enzyme,
      monomeric 23.7 kDa phosphoglycerate mutase from Schizosaccharomyces pombe.
AB  - The structure and backbone dynamics of a double labelled (15N,13C) monomeric,
      23.7 kD phosphoglycerate mutase (PGAM) from Schizosaccharomyces pombe have been
      investigated in solution using NMR spectroscopy. A set of 3125 NOE-derived
      distance restraints, 148 restraints representing inferred hydrogen bonds and 149
      values of (3)J(HNHalpha) were used in the structure calculation. The mean rmsd
      from the average structure for all backbone atoms from residues 6-205 in the best
      21 calculated structures was 0.59 A. The core of the enzyme includes an open,
      twisted, six-stranded beta-sheet flanked by four alpha-helices and a short 3(10)
      helix. An additional smaller domain contains two short antiparallel beta-strands
      and a further pair of alpha-helices. The C(alpha) atoms of the S. pombe PGAM may
      be superimposed on their equivalents in one of the four identical subunits of
      Saccharomyces cerevisiae PGAM with an rmsd of 1.34 A (0.92 A if only the beta
      sheet is considered). Small differences between the two structures are
      attributable partly to the deletion in the S. pombe sequence of a 25 residue loop
      involved in stabilising the S. cerevisiae tetramer. Analysis of 15N relaxation
      parameters indicates that PGAM tumbles isotropically with a rotational
      correlation time of 8.7 ns and displays a range of dynamic features. Of 178
      residues analysed, only 77 could be fitted without invoking terms for fast
      internal motion or chemical exchange, and out of the remainder, 77 required a
      chemical exchange term. Significantly, 46 of the slowly exchanging (milli- to
      microsecond) residues lie in helices, and these account for two-thirds of all
      analysed helix residues. On the contrary, only one beta-sheet residue required an
      exchange term. In contrast to other analyses of backbone dynamics reported
      previously, residues in slow exchange appeared to correlate with architectural
      features of the enzyme rather than congregating close to ligand binding sites.

PMID- 11237599
TI  - Identification of the domain in the human interleukin-11 receptor that mediates
      ligand binding.
AB  - The interleukin-11 receptor (IL-11R) belongs to the hematopoietic receptor
      superfamily. The functional receptor complex comprises IL-11, IL-11R and the
      signal-transducing subunit gp130. The extracellular part of the IL-11R consists
      of three domains: an N-terminal immunoglobulin-like domain, D1, and two
      fibronectin-type III-like (FNIII) domains and D2 and D3. The two FNIII domains
      comprise the cytokine receptor-homology region defined by a set of four conserved
      cysteine residues in the N-terminal domain (D2) and a WSXWS sequence motif in the
      C-terminal domain (D3). We investigated the structural and functional role of the
      third extracellular receptor domain of IL-11R. A molecular model of the human IL
      11/IL-11R complex allowed the identification of amino acid residues in IL-11R to
      be involved in ligand binding. Most of them were located in the third
      extracellular domain, which therefore should be able to bind with high affinity
      to IL-11. To prove this prediction, domain D3 of the IL-11R was expressed in
      Escherichia coli, refolded and purified. For structural characterization,
      circular dichroism, fluorescence and NMR spectroscopy were used. By plasmon
      resonance experiments, we show that the ligand-binding capacity of this domain is
      as high as that one for the whole receptor. These results provide a basis for
      further structural investigations that could be used for the rational design of
      potential agonists and antagonists essential in human therapy.

PMID- 11237601
TI  - A repeated beta-turn structure in poly(Ala-Gly) as a model for silk I of Bombyx
      mori silk fibroin studied with two-dimensional spin-diffusion NMR under off magic
      angle spinning and rotational echo double resonance.
AB  - The structure of a crystalline form of Bombyx mori silk fibroin, commonly found
      before the spinning process (known as silk I), was proposed by combining data
      obtained from two-dimensional spin-diffusion nuclear magnetic resonance under off
      magic angle spinning, rotational-echo double-resonance (REDOR), previously
      reported X-ray diffraction analyses and 13C NMR chemical shifts. Instead of B.
      mori silk fibroin with silk I structure, we used the sequential model peptide
      (Ala-Gly)15. The structure of the sequential model peptide is characterized as
      silk I after dissolving the peptide in 9 M LiBr and then dialyzing against water.
      Moreover, 13C or 15N-labeled sites may be introduced easily at any position in
      (Ala-Gly)(15) by the solid phase synthesis method for these NMR experiments. The
      torsional angles of (Ala-Gly)15 with silk I structure were determined as (-60(+/
      5) degrees, 130(+/-5) degrees ) and (70(+/-5) degrees, 30(+/-5) degrees ) for Ala
      and Gly residues, respectively. The formation of the intra-molecular hydrogen
      bonding along the chain was confirmed from REDOR NMR by determination of the
      inter-atomic distance between the nitrogen and carbon atoms comprising the intra
      molecular hydrogen bonding. The structure is named a repeated beta-turn type II
      like structure.

PMID- 11237602
TI  - Binding free energies and free energy components from molecular dynamics and
      Poisson-Boltzmann calculations. Application to amino acid recognition by aspartyl
      tRNA synthetase.
AB  - Specific amino acid binding by aminoacyl-tRNA synthetases (aaRS) is necessary for
      correct translation of the genetic code. Engineering a modified specificity into
      aminoacyl-tRNA synthetases has been proposed as a means to incorporate artificial
      amino acid residues into proteins in vivo. In a previous paper, the binding to
      aspartyl-tRNA synthetase of the substrate Asp and the analogue Asn were compared
      by molecular dynamics free energy simulations. Molecular dynamics combined with
      Poisson-Boltzmann free energy calculations represent a less expensive approach,
      suitable for examining multiple active site mutations in an engineering effort.
      Here, Poisson-Boltzmann free energy calculations for aspartyl-tRNA synthetase are
      first validated by their ability to reproduce selected molecular dynamics binding
      free energy differences, then used to examine the possibility of Asn binding to
      native and mutant aspartyl-tRNA synthetase. A component analysis of the Poisson
      Boltzmann free energies is employed to identify specific interactions that
      determine the binding affinities. The combined use of molecular dynamics free
      energy simulations to study one binding process thoroughly, followed by molecular
      dynamics and Poisson-Boltzmann free energy calculations to study a series of
      related ligands or mutations is proposed as a paradigm for protein or ligand
      design. The binding of Asn in an alternate, "head-to-tail" orientation observed
      in the homologous asparagine synthetase is analyzed, and found to be more stable
      than the "Asp-like" orientation studied earlier. The new orientation is probably
      unsuitable for catalysis. A conserved active site lysine (Lys198 in Escherichia
      coli) that recognizes the Asp side-chain is changed to a leucine residue, found
      at the corresponding position in asparaginyl-tRNA synthetase. It is interesting
      that the binding of Asp is calculated to increase slightly (rather than to
      decrease), while that of Asn is calculated, as expected, to increase strongly, to
      the same level as Asp binding. Insight into the origin of these changes is
      provided by the component analyses. The double mutation (K198L,D233E) has a
      similar effect, while the triple mutation (K198L,Q199E,D233E) reduces Asp binding
      strongly. No binding measurements are available, but the three mutants are known
      to have no ability to adenylate Asn, despite the "Asp-like" binding affinities
      calculated here. In molecular dynamics simulations of all three mutants, the Asn
      ligand backbone shifts by 1-2 A compared to the experimental Asp:AspRS complex,
      and significant side-chain rearrangements occur around the pocket. These could
      reduce the ATP binding constant and/or the adenylation reaction rate, explaining
      the lack of catalytic activity in these complexes. Finally, Asn binding to AspRS
      with neutral K198 or charged H449 is considered, and shown to be less favorable
      than with the charged K198 and neutral H449 used in the analysis.

PMID- 11237603
TI  - Exploration of partially unfolded states of human alpha-lactalbumin by molecular
      dynamics simulation.
AB  - Molecular dynamics simulations are used to probe the properties of non-native
      states of the protein human alpha-lactalbumin (human alpha-LA) with a detailed
      atomistic model in an implicit aqueous solvent environment. To sample the
      conformational space, a biasing force is introduced that increases the radius of
      gyration relative to the native state and generates a large number of low-energy
      conformers that differ in terms of their root-mean-square deviation, for a given
      radius of gyration. The resulting structures are relaxed by unbiased simulations
      and used as models of the molten globule and partly denatured states of human
      alpha-LA, based on measured radii of gyration obtained from nuclear magnetic
      resonance experiments. The ensembles of structures agree in their overall
      properties with experimental data available for the human alpha-LA molten globule
      and its more denatured states. In particular, the simulation results show that
      the native-like fold of the alpha-domain is preserved in the molten globule.
      Further, a considerable proportion of the antiparallel beta-strand in the beta
      domain are present. This indicates that the lack of hydrogen exchange protection
      found experimentally for the beta-domain is due to rearrangement of the beta
      sheet involving transient populations of non-native beta-structures. The
      simulations also provide details concerning the ensemble of structures that
      contribute as the molten globule unfolds and shows, in accord with experimental
      data, that unfolding is not cooperative; i.e. the various structural elements do
      not unfold simultaneously.

PMID- 11237604
TI  - Non-alpha-helical elements modulate polytopic membrane protein architecture.
AB  - In "all alpha-fold" transmembrane proteins, including ion channels, G-protein
      coupled receptors (GPCRs), bacterial rhodopsins and photosynthetic reaction
      centers, relatively long alpha-helices, straight, curved or kinked, pack into
      compact elliptical or circular domains. Using both existing and newly developed
      tools to analyze transmembrane segments of all available membrane protein three
      dimensional structures, including that very recently elucidated for the GPCR,
      rhodopsin, we report here the finding of frequent non-alpha-helical components,
      i.e. 3(10)-helices ("tight turns"), pi-helices ("wide turns") and intrahelical
      kinks (often due to residues other than proline). Often, diverse helical types
      and kinks concatenate over long segments and produce complex inclinations of
      helical axis, and/or diverse frame shifts in the "canonical", alpha-helical side
      chain pattern. Marked differences in transmembrane architecture exist even
      between seemingly structurally related proteins, such as bacteriorhodopsin and
      rhodopsin. Deconvolution of these non-canonical features into their composite
      elements is essential for understanding the pleiotropy of polytopic protein
      structure and function, and must be considered in developing valid macromolecular
      models.

PMID- 11237605
TI  - Dissecting the interaction network of multiprotein complexes by pairwise
      coexpression of subunits in E. coli.
AB  - Using the human basal transcription factors TFIID and TFIIH as examples, we show
      that pairwise coexpression of polypeptides in Escherichia coli can be used as a
      tool for the identification of specifically interacting subunits within
      multiprotein complexes. We find that coexpression of appropriate combinations
      generally leads to an increase in the solubility and stability of the
      polypeptides involved, which means that large amounts of the resulting complexes
      can immediately be obtained for subsequent biochemical and structural analysis.
      Furthermore, we demonstrate that the solubilization and/or the proper folding of
      a protein by its natural partner can be used as a monitor for deletion mapping to
      determine precise interaction domains. Coexpression can be used as an alternative
      or complementary approach to conventional techniques for interaction studies such
      as yeast two-hybrid analysis, GST pulldown and immunoprecipitation.

PMID- 11237606
TI  - Apparent two-state tendamistat folding is a sequential process along a defined
      route.
AB  - The small all-beta-sheet protein tendamistat folds and unfolds rapidly in
      apparent two-state reactions. Kinetic measurements of two tendamistat variants
      under various solvent conditions reveal, however, that folding occurs in at least
      two sequential steps through a metastable obligatory intermediate. Depending on
      the solvent conditions either step can become rate limiting. The activation
      parameters indicate that the first step represents an enthalpic barrier whereas
      the second step is an entropic barrier at 25 degrees C. Our results suggest that
      initial non-specific collapse precedes formation of native secondary and tertiary
      structure in tendamistat folding. This points at a distinct route in tendamistat
      folding and indicates that partially folded metastable intermediates might play
      an important role in the mechanism of apparent two-state folding.

PMID- 11237608
TI  - A multipartite interaction between Salmonella transcription factor sigma28 and
      its anti-sigma factor FlgM: implications for sigma28 holoenzyme destabilization
      through stepwise binding.
AB  - Transcription of the late (Class 3) flagellar promoters in Salmonella typhimurium
      is dependent upon the flagellar specific sigma factor, sigma28, encoded by the
      fliA gene. sigma28-dependent transcription is inhibited by an anti-sigma factor,
      FlgM, through a direct interaction. FlgM can bind both to free sigma28 to prevent
      it from forming a complex with core RNA polymerase, and to sigma28 holoenzyme to
      destabilize the complex. A collection of fliA mutants defective for negative
      regulation by FlgM (fliA* mutants) were isolated. This collection included 27
      substitution mutations that conferred insensitivity to FlgM in vivo. The
      distribution of mutations defined three potential FlgM binding domains in
      conserved sigma factor regions 2.1, 3.1 and 4 of sigma28. A subset of mutants
      from each region was assayed for FlgM binding and transcriptional activity in
      vitro. The results strongly support a multipartite interaction between sigma28
      and FlgM. Region 4 mutations, but not region 2.1 or 3.1 mutations, interfered
      with the ability of FlgM to destabilize sigma28 from core RNA polymerase. We
      present refined models for FlgM inhibition of sigma28, and for FlgM
      destabilization of sigma28 holoenzyme.

PMID- 11237607
TI  - Specific interactions of the telomeric protein Rap1p with nucleosomal binding
      sites.
AB  - The telomeres of Saccharomyces cerevisiae are structurally and functionally well
      characterized. Their telomeric DNA is packaged by the protein Rap1p (repressor
      activator protein 1). Rap1p is a multifunctional, sequence-specific, DNA-binding
      protein which, besides participating in the regulation of telomeres structure and
      length, is also involved in transcriptional regulation of genes essential for
      cell growth and in silencing. Whereas the long tracts of telomeric DNA repeats of
      higher eukaryotes are mostly organized in closely spaced canonical nucleosomal
      arrays, it has been proposed that the 300 base-pairs of S. cerevisiae telomeric
      DNA are organized in a large non-nucleosomal structure that has been called the
      telosome. Recently, nucleosomes have been found also in Tetrahymena thermophila
      telomeres, suggesting that, in general, telomere structural differences between
      lower and higher eukaryotes could be quantitative, rather than qualitative. Using
      an in vitro model system, we have addressed the question of whether Rap1p can
      form a stable ternary complex with nucleosomes containing telomeric binding
      sites, or competes with nucleosome core formation. The approach we have taken is
      to place a single Rap1p-binding site at different positions within a nucleosome
      core and then test the binding of Rap1p and its DNA-binding domain (Rap1p-DBD).
      We show here that both proteins are able to specifically recognize their
      nucleosomal binding site, but that binding is dependent on the location of the
      site within the nucleosome core structure. These results show that a ternary
      complex between a nucleosome and Rap1p is stable and could be a possible
      intermediate between telomeric nucleosomes and telosomes in the dynamics of S.
      cerevisiae telomere organization.

PMID- 11237609
TI  - Structural alterations in the DNA ahead of the primer terminus during
      displacement synthesis by reverse transcriptases.
AB  - Unlike most DNA polymerases, reverse transcriptases can initiate DNA synthesis at
      a single-strand break and displace the downstream non- template strand
      simultaneously with extension of the primer. This reaction is important for
      generation of the long terminal repeat sequences in the duplex DNA product of
      retroviral reverse transcription. Oligonucleotide-based model displacement
      constructs were used to study the interaction of human immunodeficiency virus
      type 1 and Moloney murine leukemia virus reverse transcriptases with the DNA.
      Under conditions where the DNA is saturated with enzyme, there is no protection
      against DNase I cleavage of the 5' single-stranded extension that would
      correspond to the already-displaced strand. However, the DNase I footprint on the
      non-template strand extends from the +1 to the +9 position for the human
      immunodeficiency virus type 1 enzyme and from +1 to +7 or +8 for the Moloney
      enzyme. This extent of protection on the non-template strand is similar to what
      was observed previously for the template strand downstream from the primer
      terminus. Use of potassium permanganate as a probe for unpaired bases in the
      region ahead of the primer terminus reveals that the two base-pairs immediately
      in front of the enzyme are melted by the bound enzyme. These findings are
      consistent with a displacement mechanism in which the reverse transcriptase plays
      an active role in unpairing the DNA ahead of the translocating polymerase. The
      results are interpreted in light of a recent crystal structure showing the nature
      of the protein-DNA contacts with the template strand ahead of the primer
      terminus.

PMID- 11237610
TI  - Monomer/dimer ratios of replication protein modulate the DNA strand-opening in a
      replication origin.
AB  - DNA opening is an essential step in the initiation of replication via the Cairns
      mode of replication. The opening reaction was investigated in a gamma ori system
      by using hyperactive variants of plasmid R6K-encoded initiator protein, pi.
      Reactivity to KMnO4 (indicative of opening) within gamma ori DNA occurred in both
      strands of a superhelical template upon the combined addition of wt pi, DnaA and
      integration host factor (IHF), each protein known to specifically bind gamma ori.
      IHF, examined singly, enhanced reactivity to KMnO4. The IHF-dependent reactive
      residues, however, are distinct from those dependent on pi (wt and hyperactive
      variants). Remarkably, the DNA helix opening does not require IHF and/or DnaA
      when hyperactive variants of pi were used instead of wt protein. We present three
      lines of evidence consistent with the hypothesis that DNA strand separation is
      facilitated by pi monomers despite the fact that both monomers and dimers of the
      protein can bind to iterons (pi binding sites). Taken together, our data suggest
      that pi elicits its ability to modulate plasmid copy number at the DNA helix
      opening step.

PMID- 11237612
TI  - Locking the ATP-operated clamp of DNA gyrase: probing the mechanism of strand
      passage.
AB  - DNA gyrase catalyses DNA supercoiling by passing one segment of DNA (the T
      segment) through another (the G segment) in a reaction coupled to the binding and
      hydrolysis of ATP. The N-terminal domains of the gyrase B dimer constitute an ATP
      operated clamp that is proposed to capture the T segment during the DNA
      supercoiling reaction. We have locked this clamp in the closed conformation using
      the non-hydrolysable ATP analogue ADPNP (5'-adenylyl beta,gamma
      imidodiphosphate). The clamp-locked enzyme is able to bind and cleave DNA, albeit
      at a reduced level. Although the locked enzyme is not capable of carrying out DNA
      supercoiling, it can catalyse limited DNA relaxation, consistent with the ability
      to complete one strand passage event per enzyme molecule via entry of the T
      segment through the exit gate of the enzyme. The DNA-protein complex of the clamp
      locked enzyme has a conformation that differs from the normal positively wrapped
      conformation of the gyrase-DNA complex. These experiments confirm the role of the
      ATP-operated clamp in the strand-passage reactions of gyrase and suggest a model
      for the interaction of DNA with gyrase in which a conformation with the T segment
      in equilibrium across the DNA gate can be achieved via T-segment entry through
      the ATP-operated clamp or through the exit gate.

PMID- 11237611
TI  - MSH-MLH complexes formed at a DNA mismatch are disrupted by the PCNA sliding
      clamp.
AB  - In the yeast Saccharomyces cerevisiae, mismatch repair (MMR) is initiated by the
      binding of heterodimeric MutS homolog (MSH) complexes to mismatches that include
      single nucleotide and loop insertion/deletion mispairs. In in vitro experiments,
      the mismatch binding specificity of the MSH2-MSH6 heterodimer is eliminated if
      ATP is present. However, addition of the MutL homolog complex MLH1-PMS1 to
      binding reactions containing MSH2-MSH6, ATP, and mismatched substrate results in
      the formation of a stable ternary complex. The stability of this complex suggests
      that it represents an intermediate in MMR that is subsequently acted upon by
      other MMR factors. In support of this idea, we found that the replication
      processivity factor proliferating cell nuclear antigen (PCNA), which plays a
      critical role in MMR at step(s) prior to DNA resynthesis, disrupted preformed
      ternary complexes. These observations, in conjunction with experiments performed
      with streptavidin end-blocked mismatch substrates, suggested that PCNA interacts
      with an MSH-MLH complex formed on DNA mispairs.

PMID- 11237613
TI  - Sp1 and Sp3 physically interact and co-operate with GABP for the activation of
      the utrophin promoter.
AB  - The utrophin gene codes for a large cytoskeletal protein closely related to
      dystrophin which, in the absence of dystrophin, can functionally substitute it.
      Utrophin is transcribed by two independently regulated promoters about 50 kb
      apart. The upstream promoter is TATA-less and contains a functional GABP binding
      site which, in muscle, restricts the promoter activity to post-synaptic nuclei.
      Transient transfections analysis of mutant promoters in rhabdomyosarcoma cells
      showed that the upstream promoter contains three functional GC elements that are
      recognised by Sp1 and Sp3 factors in vitro. Co-transfections of the promoter with
      Sp1, Sp3 and GABP factors in Drosophila SL2 Schneider cells, which lack of
      endogenous Sp factors, demonstrated that both Sp1 and Sp3 are positive regulators
      of the utrophin promoter and that they activate transcription synergistically
      with GABP. Consistent with this result, we observed physical interaction of both
      Sp factors with the GABPalpha subunit in vitro. Functional domain interaction
      analysis of Sp1 and Sp3 revealed that both factors interact with GABPalpha
      through their DNA binding zinc finger domain. The modulation and correct
      interaction between Sp1, Sp3 and GABP in muscle cells may be critical for the
      regulation of the utrophin promoter, and provide new targets for therapies of
      Duchenne muscular dystrophy.

PMID- 11237614
TI  - Multi-site phosphorylation of Pho4 by the cyclin-CDK Pho80-Pho85 is semi
      processive with site preference.
AB  - As part of a nutrient-responsive signaling pathway, the budding yeast cyclin-CDK
      complex Pho80-Pho85 phosphorylates the transcription factor Pho4 on five sites
      and inactivates it. Here, we describe the kinetic reaction between Pho80-Pho85
      and Pho4. Through experimentation and computer modeling we have determined that
      Pho80-Pho85 phosphorylates Pho4 in a semi-processive fashion that results from a
      balance between kcat and k(off). In addition, we show that Pho80-Pho85
      phosphorylates certain sites preferentially. Phosphorylation of the site with the
      highest preference inhibits the transcriptional activity of Pho4 when it is in
      the nucleus, while phosphorylation of the lowest-preference sites is required for
      export of Pho4 from the nucleus. This method of phosphorylation may allow Pho80
      Pho85 to quickly inactivate Pho4 in the nucleus and efficiently phosphorylate
      Pho4 to completion.

PMID- 11237615
TI  - Axial structure of the heterotypic collagen fibrils of vitreous humour and
      cartilage.
AB  - We have compared the axial structures of negatively stained heterotypic, type II
      collagen-containing fibrils with computer-generated staining patterns.
      Theoretical negative-staining patterns were created based upon the "bulkiness" of
      the individual amino acid side-chains in the primary sequence and the D-staggered
      arrangement of the triple-helices. The theoretical staining pattern of type II
      collagen was compared and cross-correlated with the experimental staining pattern
      of both reconstituted type II collagen fibrils, and fibrils isolated from adult
      and foetal cartilage and vitreous humour. The isolated fibrils differ markedly in
      both diameter and composition. Correlations were significantly improved when a
      degree of theoretical hydroxylysine glycosylation was applied, showing for the
      first time that this type of glycosylation influences the negative-staining
      pattern of collagen fibrils. Increased correlations were obtained when
      contributions from types V/XI and IX collagen were included in the simulation
      model. The N-propeptide of collagen type V/XI and the NC2 domain of type IX
      collagen both contribute to prominent stain-excluding peaks in the gap region.
      With decreasing fibril diameter, an increase of these two peaks was observed.
      Simulations of the fibril-derived staining patterns with theoretical patterns
      composed of proportions of types II, V/XI and IX collagen confirmed that the
      thinnest fibrils (i.e. vitreous humour collagen fibrils) have the highest minor
      collagen content. Comparison of the staining patterns showed that the
      organisation of collagen molecules within vitreous humour and cartilage fibrils
      is identical. The simulation model for vitreous humour, however, did not account
      for all stain-excluding mass observed in the staining pattern; this additional
      mass may be accounted for by collagen-associated macromolecules.

PMID- 11237616
TI  - Structure of a eukaryotic decoding region A-site RNA.
AB  - The aminoglycoside antibiotics target a region of highly conserved nucleotides in
      the aminoacyl-tRNA site (A site) of 16 S RNA on the 30 S subunit. The structures
      of a prokaryotic decoding region A-site oligonucleotide free in solution and
      bound to the aminoglycosides paromomycin and gentamicin C1A have been determined.
      Here, the structure of a eukaryotic decoding region A-site oligonucleotide has
      been determined using homonuclear and heteronuclear NMR spectroscopy, and
      compared to the unbound prokaryotic rRNA structure. The two structures are
      similar, with a U1406-U1495 base-pair, a C1407-G1494 Watson-Crick base-pair, and
      a G1408-A1493 base-pair instead of the A1408-A1493 base-pair of the prokaryotic
      structure. The two structures differ in the orientation of the 1408 position with
      respect to A1493; G1408 is rotated toward the major groove, which is the binding
      pocket for aminoglycosides. The structures also differ in the stacking geometry
      of G1494 on A1493, which could have slight long-range conformational effects.

PMID- 11237617
TI  - Structural origins of aminoglycoside specificity for prokaryotic ribosomes.
AB  - Aminoglycoside antibiotics, including paromomycin, neomycin and gentamicin,
      target a region of highly conserved nucleotides in the decoding region aminoacyl
      tRNA site (A site) of 16 S rRNA on the 30 S subunit. Change of a single
      nucleotide, A1408 to G, reduces the affinity of many aminoglycosides for the
      ribosome; G1408 distinguishes between prokaryotic and eukaryotic ribosomes. The
      structures of a prokaryotic decoding region A-site oligonucleotide free in
      solution and bound to the aminoglycosides paromomycin and gentamicin C1a were
      determined previously. Here, the structure of a eukaryotic decoding region A-site
      oligonucleotide bound to paromomycin has been determined using NMR spectroscopy
      and compared to the prokaryotic A-site-paromomycin structure. A conformational
      change in three adenosine residues of an internal loop, critical for high
      affinity antibiotic binding, was observed in the prokaryotic RNA-paromomycin
      complex in comparison to its free form. This conformational change is not
      observed in the eukaryotic RNA-paromomycin complex, disrupting the binding pocket
      for ring I of the antibiotic. The lack of the conformational change supports
      footprinting and titration calorimetry data that demonstrate approximately 25-50
      fold weaker binding of paromomycin to the eukaryotic decoding-site
      oligonucleotide. Neomycin, which is much less active against Escherichia coli
      ribosomes with an A1408G mutation, binds non-specifically to the oligonucleotide.
      These results suggest that eukaryotic ribosomal RNA has a shallow binding pocket
      for aminoglycosides, which accommodates only certain antibiotics.

PMID- 11237618
TI  - Molecular topology of polycyclic aromatic carcinogens determines DNA adduct
      conformation: a link to tumorigenic activity.
AB  - We report below on the solution structures of stereoisomeric "fjord" region trans
      anti-benzo[c]phenanthrene-N2-guanine (designated (BPh)G) adducts positioned
      opposite cytosine within the (C-(BPh)G-C).(G-C-G) sequence context. We observe
      intercalation of the phenanthrenyl ring with stereoisomer-dependent
      directionality, without disruption of the modified (BPh)G.C base-pair.
      Intercalation occurs to the 5' side of the modified strand for the 1S
      stereoisomeric adduct and to the 3' side for the 1R stereoisomeric adduct, with
      the S and R-trans-isomers related to one another by inversion in a mirror plane
      at all four chiral carbon atoms on the benzylic ring. Intercalation of the fjord
      region BPh ring into the helix without disruption of the modified base-pair is
      achieved through buckling of the (BPh)G.C base-pair, displacement of the linkage
      bond from the plane of the (BPh)G base, adaptation of a chair pucker by the BPh
      benzylic ring and the propeller-like deviation from planarity of the BPh
      phenanthrenyl ring. It is noteworthy that intercalation without base-pair
      disruption occurs from the minor groove side for S and R-trans-anti BPh-N2
      guanine adducts opposite C, in contrast to our previous demonstration of
      intercalation without modified base-pair disruption from the major groove side
      for S and R-trans-anti BPh-N6-adenine adducts opposite T. Further, these results
      on fjord region 1S and 1R-trans-anti (BPh)G adducts positioned opposite C are in
      striking contrast to earlier research with "bay" region benzo[a]pyrene-N2-guanine
      (designated (BP)G) adducts positioned opposite cytosine, where 10S and 10R-trans
      anti stereoisomers were positioned with opposite directionality in the minor
      groove without modified base-pair disruption. They also are in contrast to the
      10S and 10R-cis-anti stereoisomers of (BP)G adducts opposite C, where the pyrenyl
      ring is intercalated into the helix with directionality, but the modified base
      and its partner on the opposite strand are displaced out of the helix. These
      results are especially significant given the known greater tumorigenic potential
      of fjord region compared to bay region polycyclic aromatic hydrocarbons. The
      tumorigenic potential has been linked to repair efficiency such that bay region
      adducts can be readily repaired while their fjord region counterparts are
      refractory to repair. Our structural results propose a link between DNA adduct
      conformation and repair-dependent mutagenic activity, which could ultimately
      translate into structure-dependent differences in tumorigenic activities. We
      propose that the fjord region minor groove-linked BPh-N2-guanine and major groove
      linked BPh-N6-adenine adducts are refractory to repair based on our observations
      that the phenanthrenyl ring intercalates into the helix without modified base
      pair disruption. The helix is therefore minimally perturbed and the phenanthrenyl
      ring is not available for recognition by the repair machinery. By contrast, the
      bay region BP-N2-G adducts are susceptible to repair, since the repair machinery
      can recognize either the pyrenyl ring positioned in the minor groove for the
      trans-anti groove-aligned stereoisomers, or the disrupted modified base-pair for
      the cis-anti base-displaced intercalated stereoisomers.

PMID- 11237619
TI  - Solution structure of an A-tract DNA bend.
AB  - The solution structure of a DNA dodecamer d(GGCAAAAAACGG)/d(CCGTTTTTTGCC)
      containing an A-tract has been determined by NMR spectroscopy with residual
      dipolar couplings. The structure shows an overall helix axis bend of 19 degrees
      in a geometry consistent with solution and gel electrophoresis experiments.
      Fourteen degrees of the bending occurs in the GC regions flanking the A-tract.
      The remaining 5 degrees is spread evenly over its six AT base-pairs. The A-tract
      is characterized by decreasing minor groove width from the 5' to the 3' direction
      along the A strand. This is a result of propeller twist in the AT pairs and the
      increasing negative inclination of the adenine bases at the 3' side of the run of
      adenine bases. The four central thymine bases all have negative inclination
      throughout the A-tract with an average value of -6.1 degrees. Although this
      negative inclination makes the geometry of the A-tract different from all X-ray
      structures, the proton on N6 of adenine and the O4 of thymine one step down the
      helix are within distance to form bifurcated hydrogen bonds. The 5' bend of 4
      degrees occurs at the junction between the GC flank and the A-tract through a
      combination of tilt and roll. The larger 3' bend, 10 degrees, occurs in two base
      steps: the first composed of tilt, -4.1 degrees, and the second a combination of
      tilt, -4.2 degrees, and roll, 6.0 degrees. This second step is a direct
      consequence of the change in inclination between an adjacent cytosine base, which
      has an inclination of -12 degrees, and the next base, a guanine, which has 3
      degrees inclination. This bend is a combination of tilt and roll. The large
      change in inclination allows the formation of a hydrogen bond between the protons
      of N4 of the 3' cytosine and the O6 of the next 3' base, a guanine, stabilizing
      the roll component in the bend. These structural features differ from existing
      models for A-tract bends.For comparison, we also determined the structure of the
      control sequence, d(GGCAAGAAACGG)/d(CCGTTTCTTGCC), with an AT to GC transition in
      the center of the A-tract. This structure has no negative inclination in most of
      the bases within the A-tract, resulting in a bend of only 9 degrees. When ligated
      in phase, the control sequence has nearly normal mobility in gel electrophoresis
      experiments.

PMID- 11237620
TI  - X-ray structure analysis and crystallographic refinement of lumazine synthase
      from the hyperthermophile Aquifex aeolicus at 1.6 A resolution: determinants of
      thermostability revealed from structural comparisons.
AB  - An open reading frame optimized for expression of 6,7-dimethyl-8-ribityl-lumazine
      synthase of the hyperthermophilic bacterium Aquifex aeolicus in Escherichia coli
      was synthesized and expressed in a recombinant E. coli strain to a level of
      around 15 %. The recombinant protein was purified by heat-treatment and gel
      filtration. The protein was crystallized in the cubic space group I23 with the
      cell dimensions a = b = c = 180.8 A, and diffraction data were collected to 1.6 A
      resolution. The structure was solved by molecular replacement using lumazine
      synthase from Bacillus subtilis as search model. The structure of the A. aeolicus
      enzyme was refined to a resolution of 1.6 A. The spherical protein consists of 60
      identical subunits with strict icosahedral 532 symmetry. The subunit fold is
      closely related to that of the B. subtilis enzyme (rmsd 0.80 A). The extremely
      thermostable lumazine synthase from A. aeolicus has a melting temperature of
      119.9 degrees C. Compared to other icosahedral and pentameric lumazine synthases,
      the A. aeolicus enzyme has the largest accessible surface presented by charged
      residues and the smallest surface presented by hydrophobic residues. It also has
      the largest number of ion-pairs per subunit. Two ion-pair networks involving two,
      respectively three, stacking arginine residues assume a distinct role in linking
      adjacent subunits. The findings indicate the influence of the optimization of
      hydrophobic and ionic contacts in gaining thermostability.

PMID- 11237621
TI  - Crystal structures of the maltodextrin/maltose-binding protein complexed with
      reduced oligosaccharides: flexibility of tertiary structure and ligand binding.
AB  - The structure of the maltodextrin or maltose-binding protein, an initial receptor
      for bacterial ABC-type active transport and chemotaxis, consists of two globular
      domains that are separated by a groove wherein the ligand is bound and enclosed
      by an inter-domain rotation. Here, we report the determination of the crystal
      structures of the protein complexed with reduced maltooligosaccharides
      (maltotriitol and maltotetraitol) in both the "closed" and "open" forms. Although
      these modified sugars bind to the receptor, they are not transported by the wild
      type transporter. In the closed structures, the reduced sugars are buried in the
      groove and bound by both domains, one domain mainly by hydrogen-bonding
      interactions and the other domain primarily by non-polar interactions with
      aromatic side-chains. In the open structures, which abrogate both cellular
      activities of active transport and chemotaxis because of the large separation
      between the two domains, the sugars are bound almost exclusively to the domain
      rich in aromatic residues. The binding site for the open chain glucitol residue
      extends to a subsite that is distinct from those for the glucose residues that
      were uncovered in prior structural studies of the binding of active linear
      maltooligosaccharides. Occupation of this subsite may also account for the
      inability of the reduced oligosaccharides to be transported. The structures
      reported here, combined with those previously determined for several other
      complexes with active oligosaccharides in the closed form and with cyclodextrin
      in the open form, revealed at least four distinct modes of ligand binding but
      with only one being functionally active. This versatility reflects the
      flexibility of the protein, from very large motions of interdomain rotation to
      more localized side-chain conformational changes, and adaptation by the
      oligosaccharides as well.

PMID- 11237622
TI  - Structural characterization of the N-terminal oligomerization domain of the
      bacterial chromatin-structuring protein, H-NS.
AB  - The H-NS protein plays a key role in condensing DNA and modulating gene
      expression in bacterial nucleoids. The mechanism by which this is achieved is
      dependent, at least in part, on the oligomerization of the protein. H-NS consists
      of two distinct domains; the N-terminal domain responsible for protein
      oligomerization, and the C-terminal DNA binding domain, which are separated by a
      flexible linker region. We present a multidimensional NMR study of the amino
      terminal 64 residues of H-NS (denoted H-NS1-64) from Salmonella typhimurium,
      which constitute the oligomerization domain. This domain exists as a homotrimer,
      which is predicted to be self-associated through a coiled-coil configuration. NMR
      spectra show an equivalent magnetic environment for each monomer indicating that
      the polypeptide chains are arranged in parallel with complete 3-fold symmetry.
      Despite the limited resonance dispersion, an almost complete backbone assignment
      for 1H(N), 1H(alpha), 15N, 13CO and 13C(alpha) NMR resonances was obtained using
      a suite of triple resonance experiments applied to uniformly 15N-, 13C/15N- and
      2H/13C/15N-labelled H-NS1-64 samples. The secondary structure of H-NS1-64 has
      been identified on the basis of the analysis of 1H(alpha), 13C(alpha), 13Cbeta
      and 13CO chemical shifts, NH/solvent exchange rates, intra-chain H(N)-H(N) and
      medium-range nuclear Overhauser enhancements (NOEs). Within the context of the
      homotrimer, each H-NS1-64 protomer consists of three alpha-helices spanning
      residues 2-8, 12-20 and 22-53, respectively. A topological model is presented for
      the symmetric H-NS1-64 trimer based upon the combined analysis of the helical
      elements and the pattern of backbone amide group 15N nuclear relaxation rates
      within the context of axially asymmetric diffusion tensor. In this model, the
      longest of the three helices (helix 3, residues 22-53) forms a coiled-coil
      interface with the other chains in the homotrimer. The two shorter N-terminal
      helices fold back onto the outer surface of the coiled-coil core and potentially
      act to stabilise this configuration.

PMID- 11237623
TI  - Protein-protein association: investigation of factors influencing association
      rates by brownian dynamics simulations.
AB  - The rate of protein-protein association limits the response time due to protein
      protein interactions. The bimolecular association rate may be diffusion
      controlled or influenced, and in such cases, Brownian dynamics simulations of
      protein-protein diffusional association may be used to compute association rates.
      Here, we report Brownian dynamics simulations of the diffusional association of
      five different protein-protein pairs: barnase and barstar, acetylcholinesterase
      and fasciculin-2, cytochrome c peroxidase and cytochrome c, the HyHEL-5 antibody
      and hen egg lysozyme (HEL), and the HyHEL-10 antibody and HEL. The same protocol
      was used to compute the diffusional association rates for all the protein pairs
      in order to assess, by comparison to experimentally measured rates, whether the
      association of these proteins can be explained solely on the basis of diffusional
      encounter. The simulation protocol is similar to those previously derived for
      simulation of the association of barnase and barstar, and of acetylcholinesterase
      and fasciculin-2; these produced results in excellent agreement with experimental
      data for these protein pairs, with changes in association rate due to mutations
      reproduced within the limits of expected computational and modeling errors. Here,
      we find that for all protein pairs, the effects of mutations can be well
      reproduced by the simulations, even though the degree of the electrostatic
      translational and orientational steering varies widely between the cases.
      However, the absolute values of association rates for the acetylcholinesterase:
      fasciculin-2 and HyHEL-10 antibody: HEL pairs are overestimated. Comparison of
      bound and unbound protein structures shows that this may be due to gating
      resulting from protein flexibility in some of the proteins. This may lower the
      association rates compared to their bimolecular diffusional encounter rates.

PMID- 11237624
TI  - Role of counterion condensation in folding of the Tetrahymena ribozyme. I.
      Equilibrium stabilization by cations.
AB  - Folding of RNA into an ordered, compact structure requires substantial
      neutralization of the negatively charged backbone by positively charged
      counterions. Using a native gel electrophoresis assay, we have examined the
      effects of counterion condensation upon the equilibrium folding of the
      Tetrahymena ribozyme. Incubation of the ribozyme in the presence of mono-, di-
      and trivalent ions induces a conformational state that is capable of rapidly
      forming the native structure upon brief exposure to Mg2+. The cation
      concentration dependence of this transition is directly correlated with the
      charge of the counterion used to induce folding. Substrate cleavage assays
      confirm the rapid onset of catalytic activity under these conditions. These
      results are discussed in terms of classical counterion condensation theory. A
      model for folding is proposed which predicts effects of charge, ionic radius and
      temperature on counterion-induced RNA folding transitions.

PMID- 11237625
TI  - Dynamic interaction of cAMP with the Rap guanine-nucleotide exchange factor
      Epac1.
AB  - Epac1 is a Rap-specific guanine-nucleotide exchange factor (GEF) which is
      activated by the binding of cAMP to a cyclic nucleotide monophosphate (cNMP)
      binding domain. We investigated the equilibrium and dynamics of the interaction
      of cAMP and Epac1 using a newly designed fluorescence analogue of cAMP, 8-MABA
      cAMP. We observed that the interaction of cAMP, measured by competition with 8
      MABA-cAMP, with an isolated cNMP binding domain of Epac1 has an overall
      equilibrium constant (Kd) of 4 microM and that the kinetics of the interaction
      are highly dynamic. The binding properties of cAMP are apparently not affected
      when the catalytic domain is present, despite the fact that binding of cAMP
      results in activation of Epac1. This indicates that for the activation process,
      no appreciable binding energy is required. However, when bound to Rap1b, the
      apparent Kd of Epac to cAMP was about fivefold lower, suggesting that substrate
      interaction stabilizes cAMP binding. Since the fluorescent analogues used here
      were either less able or unable to induce activation of Epac1, we concluded that
      the binding of nucleotide to Epac and the activation of GEF activity are
      uncoupled processes and that thus appropriate cAMP analogues can be used as
      inhibitors of the Epac1-mediated signal transduction pathway of Rap.

PMID- 11237626
TI  - Thermodynamics of the high-affinity interaction of TCF4 with beta-catenin.
AB  - The formation of a complex between beta-catenin and members of the TCF/LEF family
      of high-mobility group proteins is a key regulatory event in the wnt-signaling
      pathway, essential for embryonal development as well as the growth of normal and
      malignant colon epithelium. We have characterized the binding of TCF4 to human
      beta-catenin by steady-state intrinsic fluorescence quenching experiments,
      surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC).
      Binding studies in solution and in heterogeneous phase showed that TCF4 binds
      reversibly to beta-catenin with an affinity (KB) of 3(+/-1) 10(8) M(-1). Site
      directed mutagenesis, together with calorimetric measurements, revealed that
      residue D16 in TCF4 plays a crucial role in high-affinity binding. Mutation of
      this residue to alanine resulted in a decrease of KB by two orders of magnitude
      as well as a significant reduction in binding enthalpy. Binding of TCF4 to beta
      catenin gave rise to a large negative enthalpy change at 25 degrees C (-29.7
      kcal/mol). Binding enthalpies were strongly temperature dependent, which resulted
      in the determination of a large heat capacity change upon binding of -1.5
      kcal/(mol K). The molecular events that take place upon complex formation are
      discussed using the measured thermodynamic data together with the crystal
      structure of the beta-catenin arm repeat region/TCF complex.

PMID- 11237627
TI  - Prospects for ab initio protein structural genomics.
AB  - We present the results of a large-scale testing of the ROSETTA method for ab
      initio protein structure prediction. Models were generated for two independently
      generated lists of small proteins (up to 150 amino acid residues), and the
      results were evaluated using traditional rmsd based measures and a novel measure
      based on the structure-based comparison of the models to the structures in the
      PDB using DALI. For 111 of 136 all alpha and alpha/beta proteins 50 to 150
      residues in length, the method produced at least one model within 7 A rmsd of the
      native structure in 1000 attempts. For 60 of these proteins, the closest
      structure match in the PDB to at least one of the ten most frequently generated
      conformations was found to be structurally related (four standard deviations
      above background) to the native protein. These results suggest that ab initio
      structure prediction approaches may soon be useful for generating low resolution
      models and identifying distantly related proteins with similar structures and
      perhaps functions for these classes of proteins on the genome scale.

PMID- 11237628
TI  - Mechanism of relaxation enhancement of spin labels in membranes by paramagnetic
      ion salts: dependence on 3d and 4f ions and on the anions.
AB  - Progressive saturation EPR measurements and EPR linewidth determinations have
      been performed on spin-labeled lipids in fluid phospholipid bilayer membranes to
      elucidate the mechanisms of relaxation enhancement by different paramagnetic ion
      salts. Such paramagnetic relaxation agents are widely used for structural EPR
      studies in biological systems, particularly with membranes. Metal ions of the 3d
      and 4f series were used as their chloride, sulfate, and perchlorate salts. For a
      given anion, the efficiency of relaxation enhancement is in the order Mn(2+) > or
      = Cu(2+) > Ni(2+) > Co(2+) approximately Dy(3+). A pronounced dependence of the
      paramagnetic relaxation enhancement on the anion is found in the order ClO(-)(4)
      > Cl(-) > SO(2-)(4). This is in the order of the octanol partition coefficients
      multiplied by spin exchange rate constants that were determined for the different
      paramagnetic salts in methanol. Detailed studies coupled with theoretical
      estimates reveal that, for the chlorides and perchlorates of Ni(2+) (and Co(2+)),
      the relaxation enhancements are dominated by Heisenberg spin exchange
      interactions with paramagnetic ions dissolved in fluid membranes. The dependence
      on membrane composition of the relaxation enhancement by intramembrane Heisenberg
      exchange indicates that the diffusion of the ions within the membrane takes place
      via water-filled defects. For the corresponding Cu(2+) salts, additional
      relaxation enhancements arise from dipolar interactions with ions within the
      membrane. For the case of Mn(2+) salts, static dipolar interactions with
      paramagnetic ions in the aqueous phase also make a further appreciable
      contribution to the spin-label relaxation enhancement. On this basis, different
      paramagnetic agents may be chosen to optimize sensitivity to different
      structurally correlated interactions. These results therefore will aid further
      spin-label EPR studies in structural biology.

PMID- 11237629
TI  - Double-quantum excitation in the NMR of spinning solids by pulse-assisted
      rotational resonance.
AB  - We describe a new technique for double-quantum excitation in magic-angle-spinning
      NMR of powdered solids. The technique is designed to efficiently excite double
      quantum coherence in the vicinity of a rotational resonance condition. The offset
      from rotational resonance allows the double-quantum filtered signals to be
      observed with high resolution and sensitivity. The method uses rotational
      excitation of zero-quantum coherence, assisted by radiofrequency pulse cycles.
      The zero-quantum coherence is converted into double-quantum coherence by a
      frequency-selective inversion sequence. Experiments on [(13)C(2), (15)N]-glycine
      demonstrate a double-quantum filtering efficiency of approximately 41% at a
      sample rotation frequency of 8.300 kHz, which is 1.600 kHz away from the n = 1
      rotational resonance. We achieve 32% double-quantum filtering efficiency at a
      spinning frequency of 9.250 kHz, which is 2.550 kHz away from rotational
      resonance.

PMID- 11237630
TI  - Site-selective electron nuclear double resonance in the exchange-narrowed regime
      of the ESR in conducting solids.
AB  - Electron nuclear magnetic double resonance on conduction electrons reveals the
      hyperfine interaction hidden by the fast electron spin exchange. We used the
      Overhauser shift technique to investigate the electron spin density of the
      conduction band of gallium oxide, beta-Ga(2)O(3). Due to the monoclinic
      structure, the conduction band of beta-Ga(2)O(3) is anisotropic and it is
      dominated by contributions from the two nonequivalent Ga sites. The large
      quadrupole couplings of the two gallium isotopes (69)Ga and (71)Ga (both with I =
      3/2) are completely resolved in our double-resonance experiments. This resolved
      quadrupole interaction allows the determination of the electric field gradients
      at both gallium sites with high precision and high sensitivity. The resolved
      quadrupole splitting is the key to the site-selected determination of the
      hyperfine interaction. The concepts behind these double-resonance techniques are
      rather general and should be applicable in similar semiconductor systems.

PMID- 11237631
TI  - Computer simulation of the spin-echo spatial distribution in the case of
      restricted self-diffusion.
AB  - This article concerns the question of a proper stochastic treatment of the spin
      echo self-diffusion attenuation of confined particles that arises when short
      gradient pulse approximation fails. Diffusion is numerically simulated as a
      succession of random steps when motion is restricted between two perfectly
      reflecting parallel planes. With the magnetic field gradient perpendicular to the
      plane boundaries, the spatial distribution of the spin-echo signal is calculated
      from the simulated trajectories. The diffusion propagator approach (Callaghan,
      "Principles of Nuclear Magnetic Resonance Microscopy," Oxford Univ. Press,
      Oxford, 1991), which is just the same as the evaluation of the spin-echo
      attenuation by the method of cumulant expansion in the Gaussian approximation,
      with Einstein's approximation of the velocity correlation function (VCF) (delta
      function), agrees with the results of simulation only for the particle
      displacements that are much smaller than the size of the confinement. A strong
      deviation from the results of the simulation appears when the bouncing rate from
      the boundaries increases at intermediate and long gradient sequences. A better
      fit, at least for intermediate particle displacements, was obtained by replacing
      the VCF with the Oppenheim--Mazur solution of the Langevin equation (Oppenheim
      and Mazur, Physica 30, 1833--1845, 1964), which is modified in a way to allow for
      spatial dependence of particle displacements. Clearly, interplay of the
      correlation dynamics and the boundary conditions is taking place for large
      diffusion displacements. However, the deviation at long times demonstrates a
      deficiency of the Gaussian approximation for the spin echo of diffusion inside
      entirely closed pores. Here, the cumulants higher than the second one might not
      be negligible. The results are compared with the experiments on the edge
      enhancement by magnetic resonance imaging of a pore.

PMID- 11237632
TI  - NMR paramagnetic relaxation enhancement: test of the controlling influence of zfs
      rhombicity for S = 1.
AB  - Prior theoretical work has predicted that the NMR paramagnetic relaxation
      enhancement (NMR-PRE) produced by electron spin S = 1 ions is highly sensitive to
      orthorhombic terms in the static zero field splitting (zfs) tensor. Zfs
      orthorhombicity (which implies chemical inequivalence of the three principal
      directions of the zfs-principal axis system and is described by the zfs E
      parameter) is predicted to suppress the NMR-PRE profoundly relative to the
      reference cylindrical zfs-limit situation. This expectation was tested
      experimentally by a comparison of the zfs-limit NMR-PRE produced by
      [Ni(II)(en)(3)](2+) (en = ethylenediamine), a trigonal complex which lacks zfs
      rhombicity, with the zfs-limit NMR-PRE produced by two orthorhombic complexes,
      [Ni(II)(en)(2)(H(2)O)(2)](2+) and [Ni(II)(en)(H(2)O)(4)](2+). As predicted, the
      zfs-limit NMR-PRE produced by the orthorhombic complexes in the proton resonance
      of a dioxane probe species in the solvent was strongly suppressed (by factors of
      approximately 5 and 7, respectively) relative to the comparable measurement on
      the trigonal complex. The suppression of the NMR-PRE due to the orthorhombic zfs
      terms is counteracted by an applied Zeeman field, leading to a predicted rise in
      the NMR-PRE with increasing Zeeman field strength; this rise occurs when the
      Zeeman energy is comparable to the orthorhombic zfs splitting, 2E. This second
      prediction of theory was likewise confirmed: the expected rhombicity-induced
      magnetic field dependence in the NMR-PRE was observed for the orthorhombic
      complexes but not for the trigonal complex.

PMID- 11237633
TI  - Iterative lineshape analysis of quadrupolar echo spectra of a damped CD(3)
      quantum rotor: preliminary evidence of a novel mechanism of stochastic spin
      exchange.
AB  - It is demonstrated that the wealth of information about damped quantum rotation
      of CD(3) groups, contained in quadrupolar echo spectra, can be fully explored in
      a broad temperature range using a method of iterative analysis of the spectral
      lineshapes. The recently reported lineshape equation which, apart from the
      quantum tunneling and the dissipative Alexander--Binsch terms, contains an
      additional dissipative term having no classical analog is shown to be capable of
      describing even subtle details of the spectra of a crystal of acetylsalicylic
      acid--CD(3) oriented specifically in the magnetic field. Preliminary evidence of
      the occurrence of this novel dissipative mechanism in the system studied is
      reported. The results obtained seem to suggest that there is no "classical limit"
      in the dissipative behavior of this system.

PMID- 11237634
TI  - Continuous-wave magnetic resonance imaging of short T(2) materials.
AB  - There is growing interest in the use of magnetic resonance imaging (MRI) to
      examine solid materials where the restricted motion of the probed spins leads to
      broad lines and short T(2) values, rendering many interesting systems invisible
      to conventional 2DFT pulsed imaging methods. In EPR T(2) seldom exceeds 0.1 mus
      and continuous-wave methods are adopted for spectroscopy and imaging. In this
      paper we demonstrate the use of continuous-wave MRI to obtain 2-dimensional
      images of short T(2) samples. The prototype system can image samples up to 50 mm
      in diameter by 60 mm long and has been used to image polymers and water
      penetration in porous media. Typical acquisition times range between 10 and 40
      min. Resolution of 1 to 2 mm has been achieved for samples with T(2) values
      ranging from 38 to 750 mus. There is the possibility of producing image contrast
      that is determined by the material properties of the sample.

PMID- 11237635
TI  - (13)C chemical shift and (13)C-(14)N dipolar coupling tensors determined by (13)C
      rotary resonance solid-state NMR.
AB  - This work explores the utility of simple rotary resonance experiments for the
      determination of the magnitude and orientation of (13)C chemical shift tensors
      relative to one or more (13)C--(14)N internuclear axes from (13)C magic-angle
      spinning NMR experiments. The experiment relies on simultaneous recoupling of the
      anisotropic (13)C chemical shift and (13)C--(14)N dipole--dipole coupling
      interactions using 2D rotary resonance NMR with RF irradiation on the (13)C spins
      only. The method is demonstrated by experiments and numerical simulations for the
      (13)C(alpha) spins in powder samples of L-alanine and glycine with (13)C in
      natural abundance. To investigate the potential of the experiment for
      determination of relative/absolute tensor orientations and backbone dihedral
      angles in peptides, the influence from long-range dipolar coupling to sequential
      (14)N spins in a peptide chain ((14)N(i)--(13)C(alpha)(i)--(14)N(i+1) and
      (14)N(i+1)--(13)C'(i)--(14)N(i) three-spin systems) as well as residual
      quadrupolar-dipolar coupling cross-terms is analyzed numerically.

PMID- 11237636
TI  - NMR phase noise in bitter magnets.
AB  - We have studied the temporal instability of a high field resistive Bitter magnet
      through nuclear magnetic resonance (NMR). This instability leads to transverse
      spin decoherence in repeated and accumulated NMR experiments as is normally
      performed during signal averaging. We demonstrate this effect via Hahn echo and
      Carr--Purcell--Meiboom--Gill (CPMG) transverse relaxation experiments in a 23-T
      resistive magnet. Quantitative analysis was found to be consistent with separate
      measurements of the magnetic field frequency fluctuation spectrum, as well as
      with independent NMR experiments performed in a magnetic field with a controlled
      instability. Finally, the CPMG sequence with short pulse delays is shown to be
      successful in recovering the intrinsic spin--spin relaxation even in the presence
      of magnetic field temporal instability.

PMID- 11237638
TI  - Spectral editing in (13)C MAS NMR under moderately fast spinning conditions.
AB  - Novel procedures for the spectral assignment of peaks in high-resolution solid
      state (13)C NMR are discussed and demonstrated. These methods are based on the
      observation that at moderate and already widely available rates of magic-angle
      spinning (10--14 kHz MAS), CH and CH(2) moieties behave to a large extent as if
      they were effectively isolated from the surrounding proton reservoir. Dipolar
      based analogs of editing techniques that are commonly used in liquid-state NMR
      such as APT and INEPT can then be derived, while avoiding the need for periods of
      homonuclear (1)H--(1)H multipulse decoupling. The resulting experiments end up
      being very simple, essentially tuning-free, and capable of establishing
      unambiguous distinctions among CH, CH(2), and --C--/-CH(3) carbon sites. The
      principles underlying such sequences were explored using both numerical
      calculations and experimental measurements, and once validated their editing
      applications were illustrated on a number of compounds.

PMID- 11237637
TI  - Signal-to-noise ratio comparison of encoding methods for hyperpolarized noble gas
      MRI.
AB  - Some non-Fourier encoding methods such as wavelet and direct encoding use
      spatially localized bases. The spatial localization feature of these methods
      enables optimized encoding for improved spatial and temporal resolution during
      dynamically adaptive MR imaging. These spatially localized bases, however, have
      inherently reduced image signal-to-noise ratio compared with Fourier or Hadamad
      encoding for proton imaging. Hyperpolarized noble gases, on the other hand, have
      quite different MR properties compared to proton, primarily the nonrenewability
      of the signal. It could be expected, therefore, that the characteristics of image
      SNR with respect to encoding method will also be very different from
      hyperpolarized noble gas MRI compared to proton MRI. In this article,
      hyperpolarized noble gas image SNRs of different encoding methods are compared
      theoretically using a matrix description of the encoding process. It is shown
      that image SNR for hyperpolarized noble gas imaging is maximized for any
      orthonormal encoding method. Methods are then proposed for designing RF pulses to
      achieve normalized encoding profiles using Fourier, Hadamard, wavelet, and direct
      encoding methods for hyperpolarized noble gases. Theoretical results are
      confirmed with hyperpolarized noble gas MRI experiments.

PMID- 11237639
TI  - Resonance offset tailored composite pulses.
AB  - We describe novel composite pulse sequences which act as general rotors and thus
      are particularly suitable for nuclear magnetic resonance quantum computation. The
      resonance offset tailoring to enhance nutations approach permits perfect
      compensation of off-resonance errors at two selected frequencies placed
      symmetrically around the frequency of the radiofrequency source.

PMID- 11237640
TI  - Accurate measurement of translational diffusion coefficients: a practical method
      to account for nonlinear gradients.
AB  - For NMR probes equipped with pulsed field gradient coils, which are not optimized
      for gradient linearity, the precision and accuracy of experimentally measured
      translational diffusion coefficients are limited by the linearity of the gradient
      pulses over the sample volume. This study shows that the accuracy and precision
      of measured diffusion coefficients by the Stejskal--Tanner spin-echo pulsed field
      gradient experiment can be significantly improved by mapping the gradient z
      profile and by using the mapped calibration parameters in the data analysis. For
      practical applications the gradient distribution may be approximated by a
      truncated linear distribution defined by minimum and maximum values of the
      gradient. By including the truncated linear gradient distribution function in the
      Stejskal--Tanner equation, the systematic deviation between the fitted curve and
      the experimental attenuation curve decreases by an order of magnitude. The
      gradient distribution may be calibrated using an intense NMR signal from a sample
      with a known diffusion coefficient. The diffusion coefficient of an unknown
      sample may then be determined from a two-parameter fit, using the known gradient
      distribution function.

PMID- 11237641
TI  - One-shot velocimetry using echo planar imaging microscopy.
AB  - A rapid version of PEPI (pi-echo planar imaging) velocimetry has been
      implemented, enabling a velocity image, at microscopic resolution, to be acquired
      in less than 1 s. The velocity map was reconstructed using the phase information
      from the ratio of two PEPI images, one obtained with a velocity-encoding filter
      applied prior to the imaging sequence and the other image without. The
      acquisition time for each image was about 80 ms and the two complete image
      acquisitions were acquired in one shot in 500 ms. This rapid velocimetry sequence
      gave a good representation of laminar pipe flow. It has also been used to examine
      extensional flow in a biaxial extension in which the transient extension takes
      about 3 s.

PMID- 11237642
TI  - Circular polarization excitation and detection in (14)N NQR.
AB  - Circular polarization excitation and detection of (14)N NQR signal are reported.
      A theoretical model is presented in terms of fictitious spin-1/2 operators and is
      compared to experiments performed on a powder crystalline sample of RDX. It is
      shown that in spin-1 systems with finite asymmetry--unlike previously reported
      NMR and symmetric spin-3/2 NQR systems (Chen et al., J. Magn. Reson. 54, 324-
      327, 1983; Weber and Hahn, Phys. Rev. 120, 365--375, 1960)-the circular
      polarization nature of the signal is due to powder orientation effects in
      polycrystalline samples. Sensitivity improvements up to a factor of the square
      root of 2 are reported using the same hardware and switching modes from linear
      polarization to circular polarization; this also is shown to result from the
      polycrystalline nature of the samples.

PMID- 11237643
TI  - Diffusion measurements with the aid of nutation spin echoes appearing after two
      inhomogeneous radiofrequency pulses in inhomogeneous magnetic fields.
AB  - Nutation echoes are generated by radiofrequency (RF) pulses with an inhomogeneous
      amplitude, B(1) = B(1)(r), in inhomogeneous magnetic fields, B(0) = B(0)(r). The
      two gradients of strengths G(1) and G(0), respectively, must be aligned in
      parallel for a maximum echo signal. After two RF pulses, two echoes appear at
      times tau(a) = 2 tau(1) + tau(2) + (G(1)/G(0))tau(1) and tau(b) = 2 tau(1) +
      tau(2) + 2(G(1)/G(0))tau(1), where tau(1) is the RF pulse duration and tau(2) the
      interpulse interval. It is shown that these echoes can favorably be employed for
      the determination of self-diffusion coefficients even in the poor experimental
      situation one often faces in low-resolution or low-field NMR. The signal
      intensity is comparable to that of ordinary Hahn echoes. Diffusion coefficients
      and spin-lattice relaxation times can be evaluated from the same experimental
      data set if both nutation echoes are recorded. Test experiments are in good
      agreement with literature data. Applications of the technique to "inside out"
      NMR, well logging NMR, surface coil NMR, toroid cavity NMR, etc., are suggested.

PMID- 11237644
TI  - Diffusion and relaxation effects in general stray field NMR experiments.
AB  - We analyze the evolution of magnetization following any series of radiofrequency
      pulses in strongly inhomogeneous fields, with particular attention to diffusion
      and relaxation effects. When the inhomogeneity of the static magnetic field
      approaches or exceeds the strength of the RF field, the magnetization has
      contributions from different coherence pathways. The diffusion or relaxation
      induced decay of the signal amplitude is in general nonexponential, even if the
      sample has single relaxation times T(1), T(2) and a single diffusion coefficient
      D. In addition, the shape of the echo depends on diffusion and relaxation. It is
      possible to separate contributions from different coherence pathways by phase
      cycling of the RF pulses. The general analysis is tested on stray field
      measurements using two different pulse sequences. We find excellent agreement
      between measurements and calculations. The inversion recovery sequence is used to
      study the relaxation effects. We demonstrate two different approaches of data
      analysis to extract the relaxation time T(1). Finite pulse width effects on the
      timing of the echo formation are also studied. Diffusion effects are analyzed
      using the Carr--Purcell--Meiboom--Gill sequence. In a stray field of a constant
      gradient g, we find that unrestricted diffusion leads to nonexponential signal
      decay versus echo number N, but within experimental error the diffusion
      attenuation is still only a function of g(2)Dt(3)(E)N, where t(E) is the echo
      spacing.

PMID- 11237645
TI  - Properties of the HYSCORE spin echo signal.
AB  - In hyperfine sublevel correlation spectroscopy (HYSCORE), the finite duration of
      the microwave pulses leads to an incomplete inversion of the electron spin
      magnetization by the third pulse, which results in a significant admixture of
      stimulated ESEEM to HYSCORE ESEEM. This virtually unavoidable contribution of
      stimulated ESEEM seriously hampers the analysis of the modulation amplitudes in
      HYSCORE. In this work, we analyze the properties of the spin echo signals
      contributing to the composite HYSCORE signal. Based on this analysis, we propose
      the strategies of HYSCORE data acquisition and processing that allow one to
      practically eliminate the contribution of the stimulated echo and make the
      HYSCORE ESEEM analyzable in quantitative terms.

PMID- 11237646
TI  - The effect of spin relaxation on ENDOR spectra recorded at high magnetic fields
      and low temperatures.
AB  - A simple theoretical model that describes the pulsed Davies electron-nuclear
      double resonance (ENDOR) experiment for an electron spin S = (1/2) coupled to a
      nuclear spin I = (1/2) was developed to account for unusual W-band (95 GHz) ENDOR
      effects observed at low temperatures. This model takes into account the thermal
      polarization along with all internal relaxation processes in a four-level system
      represented by the electron- and nuclear-spin relaxation times T(1e) and T(1n),
      respectively, and the cross-relaxation time, T(1x). It is shown that under
      conditions of sufficiently high thermal spin polarization, nuclei can exhibit
      asymmetric ENDOR spectra in two cases: the first when t(mix) >> T(1e) and T(1n),
      T(1x) >> T(1e), where ENDOR signals from the alpha manifold are negative and
      those of the beta manifold positive, and the second when the cross- and/or
      nuclear-relaxation times are longer than the repetition time (t(mix) << T(1e) <<
      t(R) and T(1n), T(1x) > t(R)). In that case the polarization of the ENDOR signals
      becomes opposite to the previous case, the lines in the alpha manifolds are
      positive, and those of the beta manifold are negative. This case is more likely
      to be encountered experimentally because it does not require a very long mixing
      time and is a consequence of the saturation of the nuclear transitions. Using
      this model the experimental t(mix) and t(R) dependencies of the W-band (1)H ENDOR
      amplitudes of [Cu(imidazole)(4)]Cl(2) were reproduced and the values of T(1e) and
      T(1x) >> T(1e) were determined. The presence of asymmetry in the ENDOR spectrum
      is useful as it directly provides the sign of the hyperfine coupling. The
      presented model allows the experimentalist to adjust experimental parameters,
      such as t(mix) and t(R), in order to optimize the desired appearance of the
      spectrum.

PMID- 11237647
TI  - Recoupled polarization-transfer methods for solid-state (1)H--(13)C heteronuclear
      correlation in the limit of fast MAS.
AB  - An in-depth account of the effects of homonuclear couplings and multiple
      heteronuclear couplings is given for a recently published technique for (1)H-
      (13)C dipolar correlation in solids under very fast MAS, where the heteronuclear
      dipolar coupling is recoupled by means of REDOR pi-pulse trains. The method bears
      similarities to well-known solution-state NMR techniques, which form the
      framework of a heteronuclear multiple-quantum experiment. The so-called recoupled
      polarization-transfer (REPT) technique is versatile in that rotor-synchronized
      (1)H--(13)C shift correlation spectra can be recorded. In addition, weak
      heteronuclear dipolar coupling constants can be extracted by means of spinning
      sideband analysis in the indirect dimension of the experiment. These sidebands
      are generated by rotor encoding of the reconversion Hamiltonian. We present
      generalized variants of the initially described heteronuclear multiple-quantum
      correlation (HMQC) experiment, which are better suited for certain applications.
      Using these techniques, measurements on model compounds with (13)C in natural
      abundance, as well as simulations, confirm the very weak effect of (1)H--(1)H
      homonuclear couplings on the spectra recorded with spinning frequencies of 25--30
      kHz. The effect of remote heteronuclear couplings on the spinning-sideband
      patterns of CH(n) groups is discussed, and (13)C spectral editing of rigid
      organic solids is shown to be practicable with these techniques.

PMID- 11237648
TI  - Determination of relative triplet sublevel populating rates during optical
      pumping using ODMR.
AB  - A method is introduced, based on optical detection of triplet state magnetic
      resonance (ODMR), to determine the relative populating rates of photoexcited
      triplet state sublevels during optical pumping. Phosphorescence transients
      induced by microwave rapid passage during optical pumping are analyzed globally
      utilizing kinetic parameters obtained from separate microwave-induced delayed
      phosphorescence measurements to obtain relative sublevel populating rates.
      Results are unaffected by phosphorescence from triplet populations that do not
      yield an ODMR response. The method is applied to the triplet state of the indole
      chromophore in various environments to reveal the effects of local interactions
      on the pattern of intersystem crossing. Enhanced spin--orbit coupling effects are
      attributed to interactions that reduce the planar symmetry of the indole
      chromophore.

PMID- 11237649
TI  - On neglecting chemical exchange effects when correcting in vivo (31)P MRS data
      for partial saturation.
AB  - Signal acquisition in most MRS experiments requires a correction for partial
      saturation that is commonly based on a single exponential model for T(1) that
      ignores effects of chemical exchange. We evaluated the errors in (31)P MRS
      measurements introduced by this approximation in two-, three-, and four-site
      chemical exchange models under a range of flip-angles and pulse sequence
      repetition times (T(R)) that provide near-optimum signal-to-noise ratio (SNR). In
      two-site exchange, such as the creatine-kinase reaction involving phosphocreatine
      (PCr) and gamma-ATP in human skeletal and cardiac muscle, errors in saturation
      factors were determined for the progressive saturation method and the dual-angle
      method of measuring T(1). The analysis shows that these errors are negligible for
      the progressive saturation method if the observed T(1) is derived from a three
      parameter fit of the data. When T(1) is measured with the dual-angle method,
      errors in saturation factors are less than 5% for all conceivable values of the
      chemical exchange rate and flip-angles that deliver useful SNR per unit time over
      the range T(1)/5 < or = T(R) < or = 2T(1). Errors are also less than 5% for three
      and four-site exchange when T(R) > or = T(1)(*)/2, the so-called "intrinsic"
      T(1)'s of the metabolites. The effect of changing metabolite concentrations and
      chemical exchange rates on observed T(1)'s and saturation corrections was also
      examined with a three-site chemical exchange model involving ATP, PCr, and
      inorganic phosphate in skeletal muscle undergoing up to 95% PCr depletion.
      Although the observed T(1)'s were dependent on metabolite concentrations, errors
      in saturation corrections for T(R) = 2 s could be kept within 5% for all
      exchanging metabolites using a simple interpolation of two dual-angle T(1)
      measurements performed at the start and end of the experiment. Thus, the single
      exponential model appears to be reasonably accurate for correcting (31)P MRS data
      for partial saturation in the presence of chemical exchange. Even in systems
      where metabolite concentrations change, accurate saturation corrections are
      possible without much loss in SNR.

PMID- 11237650
TI  - Two-dimensional dynamic-director (13)C NMR of liquid crystals.
AB  - A novel nuclear magnetic resonance (NMR) experiment for facilitating the
      resolution and assignment of liquid crystalline (13)C NMR spectra is described.
      The method involves the motor-driven reorientation of the liquid crystalline
      director, in synchrony with the acquisition of a 2D chemical shift correlation
      spectrum. By monitoring in this fashion the (13)C NMR evolution of spins in the
      liquid crystal at two different director orientations with respect to the
      magnetic field, the method distinguishes anisotropic from isotropic displacements
      and can be utilized for assigning the resonances and estimating local degrees of
      order. Of various potential pairs of angles suitable for such a correlation, the
      (0 degrees, 90 degrees ) choice was found to be most convenient, as it avoids
      line broadening complications that may otherwise originate from heterogeneities
      of the oriented phase. The technique thus derived was employed in the analysis of
      a series of monomeric and polymeric liquid crystal systems.

PMID- 11237651
TI  - High-precision mapping of the magnetic field utilizing the harmonic function mean
      value property.
AB  - The spatial distributions of the static magnetic field components and MR phase
      maps in space with homogeneous magnetic susceptibility are shown to be harmonic
      functions satisfying Laplace's equation. A mean value property is derived and
      experimentally confirmed on phase maps: the mean value on a spherical surface in
      space is equal to the value at the center of the sphere. Based on this property,
      a method is implemented for significantly improving the precision of MR phase or
      field mapping. Three-dimensional mappings of the static magnetic field with a
      precision of 10(-11) approximately 10(-12) T are obtained in phantoms by a 1.5-T
      clinical MR scanner, with about three-orders-of-magnitude precision improvement
      over the conventional phase mapping technique. In vivo application of the method
      is also demonstrated on human leg phase maps.

PMID- 11237652
TI  - Through-bond heteronuclear single-quantum correlation spectroscopy in solid-state
      NMR, and comparison to other through-bond and through-space experiments.
AB  - A new through-bond carbon-proton correlation technique, the MAS-J-HSQC
      experiment, is described for solid-state NMR. This new pulse scheme is compared
      experimentally with the previously proposed MAS-J-HMQC experiment in terms of
      proton resolution on a model sample of powdered L-alanine. We show that for
      natural abundance compounds, the MAS-J-HMQC and MAS-J-HSQC experiments give about
      the same proton resolution, whereas, for (13)C-labeled materials, narrower proton
      linewidths are obtained with the MAS-J-HSQC experiment. In addition we show that
      in scalar as well as in dipolar heteronuclear shift correlation experiments, when
      the proton chemical shift is encoded by the evolution of a single-quantum
      coherence, the proton resolution can be enhanced by simply adding a 180 degrees
      carbon pulse in the middle of the t(1) evolution time.

PMID- 11237653
TI  - NMR spectra of a spin-1/2 nucleus scalar coupled to two equivalent spin-1 nuclei
      in the limit of slow quadrupolar relaxation.

PMID- 11237654
TI  - Fast MAS total through-bond correlation spectroscopy.
AB  - Mixing sequences for total through-bond correlation spectroscopy in solids
      (TOBSY) were developed. The motivation is the design of broadband, effective, and
      robust sequences adapted for "fast" MAS. Possible sequences with the desired
      Hamiltonian (the homonuclear isotropic J interaction) were identified using
      lowest order average Hamiltonian theory. Numerical simulations as a function of
      the MAS frequency were then employed to further characterize the performance. An
      experimental TOBSY spectrum of a uniformly (13)C-labeled decapeptide at 20 kHz
      MAS was obtained using one of the new sequences. The spectrum allows us to assign
      the (13)C resonances to the respective spin systems.

PMID- 11237655
TI  - The STR/ort mouse and its use as a model of osteoarthritis.

PMID- 11237656
TI  - Expression of type X collagen in young and old C57Bl/6 and Balb/c mice. Relation
      with articular cartilage degeneration.
AB  - OBJECTIVE: To investigate whether the development of osteoarthritic lesions in
      the knee joints of mice is associated with increased immunostaining of type X
      collagen. METHODS: Sections of total knee joints in combination with
      immunohistochemistry were used to study the distribution of type X collagen in
      the cartilage of young and old mice of two mouse strains, Balb/c and C57Bl/6,
      known to develop osteoarthritic lesions at different locations. Expression of
      type X collagen and PTH/PTHrP-receptor mRNA were studied by RT-PCR. RESULTS:
      Young adult Balb/c and C57Bl/6 mice both expressed type X collagen in the non
      calcified cartilage of the tibia-femoral joint. Old mice of both strains had a
      strongly increased deposition of type X collagen in the patella-femoral but not
      in the tibia-femoral joint. The locations in the murine knee joints prone to
      develop osteoarthritis (OA) did not preferentially express increased amounts of
      type X collagen. Thus, whereas increased type X was observed in both strains in
      the patella-femoral joints, only Balb/c mice preferentially developed
      osteoarthritic lesions in these joints. Also cartilage degeneration was usually
      seen only in the lateral compartment of the knee joints of C57Bl/6 mice but this
      was not accompanied by increased type X collagen immunostaining. Increased
      deposition of type X collagen was not associated with elevated levels of type X
      collagen mRNA or with decreased levels of PTH/PTHrP-receptor mRNA. CONCLUSION:
      Type X collagen expression and spontaneous OA in mice are not necessarily related
      since OA prone locations in the murine knee joint do not preferentially express
      type X collagen.

PMID- 11237657
TI  - Interindividual variability and correlation among morphological parameters of
      knee joint cartilage plates: analysis with three-dimensional MR imaging.
AB  - OBJECTIVE: To determine the range and variability of the cartilage volume,
      thickness, and articular surface areas in the knee joints of healthy male
      subjects, the association of these parameters within and between the knee joint
      cartilage plates, and their correlation with anthropometric variables. METHOD:
      The right knees of 27 individuals (age 23 to 64 years) without cartilage damage
      were examined. Sagittal magnetic resonance imaging was with a fat-suppressed
      gradient echo sequence (resolution 2 x 0.31 x 0.31 mm(3)), quantitative
      parameters being computed for all cartilage plates. RESULTS: The total knee joint
      cartilage volume ranged from 16.6 to 31.4 ml, the size of the articular surfaces
      from 102 to 163 cm(2), and the mean cartilage thickness from 1.57 to 2.43 mm. The
      mean and maximal cartilage thickness were highest in the patella (2.76 and 5.72
      mm). There was a significant correlation of the cartilage volume with the mean
      thickness (R=0.80) and with the joint surface areas (R=0.56), but not between the
      thickness and surface area (R=0.37). The association among the patella, tibia,
      and femur was 0.16 to 0.72 for volumes, 0.08 to 0.78 for thickness, and 0.24 to
      0.62 for surfaces. The knee joint cartilage volume and the surface areas were
      significantly associated with the body height (R=0.51 and 0.57), but not the
      cartilage thickness (R=0.22). CONCLUSION: There is a surprisingly high
      variability of the quantitative distribution of cartilage within the knee joint,
      with only moderate correlations between knee joint cartilage plates, and this
      variability cannot be adequately predicted based on anthropometric variables.

PMID- 11237658
TI  - Quantitative analysis of gene expression in human articular cartilage from normal
      and osteoarthritic joints.
AB  - OBJECTIVE: To quantify the expression of genes encoding extracellular matrix
      (ECM) proteins in human cartilage from normal and osteoarthritic (OA) joints.
      DESIGN: Human cartilage samples were classified as control (CTR) or OA according
      to clinical evaluation and assessed histologically and biochemically to confirm
      the diagnosis. mRNAs encoding collagen types I, II and X, aggrecan, versican,
      osteopontin and osteocalcin were quantified by real-time reverse transcription
      PCR assays and normalized to a reference mRNA (GAPDH). RESULTS: RNA from native
      cartilage could be reproducibly and efficiently amplified by real-time PCR only
      if isolated using purification membranes. Primers and fluorescent probes for real
      time PCR, endowed with comparable (<6% difference from GAPDH) and high (>91%)
      amplification efficiencies, were designed and validated for the selected ECM
      genes. The expression of most genes under investigation displayed large
      variations and was not significantly different in CTR and OA cartilage. Only
      osteopontin mRNA levels were significantly higher in OA than CTR specimens. mRNA
      ratios of collagen type II to I and of aggrecan to versican, defined as indexes
      of chondrocyte differentiation, were less variable within each population than
      the single genes and markedly higher (27.0 and 7.6-fold, respectively) in CTR
      than OA cartilage, with high statistical significance (P = 0.00013 and P =
      0.00007, respectively). CONCLUSIONS: Our results provide evidence that gene
      patterns related to chondrocyte differentiation discriminate between CTR and OA
      human cartilage with higher sensitivity than single ECM genes. The method
      described here has the potential to improve understanding of the progression of
      OA and could become a valuable diagnostic tool.

PMID- 11237659
TI  - Measurement of cartilage oligomeric matrix protein (COMP) in normal and diseased
      equine synovial fluids.
AB  - OBJECTIVE: This study was designed to assay cartilage oligomeric matrix protein
      (COMP) in equine synovial fluids and to compare the concentration in synovial
      fluids from normal horses with joint diseased horses. The relationship between
      the COMP degradation and the matrix metalloproteinase activity in synovial fluids
      was also investigated. DESIGN: Using COMP antigen prepared from equine articular
      cartilage and murine monoclonal antibody (12C4) raised against human COMP, an
      inhibition ELISA was developed. COMP in equine synovial fluids from normal and
      diseased joints was quantified. Metalloproteinase activities were evaluated in
      the same synovial fluids by a gelatin degradation ELISA. COMP fragments were
      evaluated qualitatively by Western blotting. RESULTS: The COMP inhibition ELISA
      was reliable at concentrations of equine COMP between 62.5 and 2000 ng/ml. COMP
      values in joint fluids in both aseptic and septic joint disease (19.7+/-15.3 and
      16.1+/-11.2 microg/ml, respectively) were significantly (P < 0.001) lower than
      normal (53.2+/-29.0 microg/ml). The molecular sizes of COMP on immunoblots were
      different between normal and diseased synovial fluids; more fragments were seen
      in diseased fluids. The aseptic (26.6 +/- 20.6%) and septic joint disease
      synovial fluids (36.1 +/- 37.5%) had significantly higher (P < 0.02 and 0.002,
      respectively) gelatinolytic activities than normal (13.6 +/- 13.7%). There was a
      negative correlation (R = -0.31, P < 0.002) between COMP level and gelatinase
      activity. Conclusions We conclude that the fragment pattern and the absolute COMP
      concentration maybe useful for monitoring joint disease, and that COMP
      degradation in synovial fluids from progressed joint disease may be due to MMP
      gelatinolytic activity.

PMID- 11237660
TI  - Overexpression of active TGF-beta-1 in the murine knee joint: evidence for
      synovial-layer-dependent chondro-osteophyte formation.
AB  - OBJECTIVE: To investigate the impact of a prolonged and constant active TGF-beta
      expression by the synovial lining cells on cartilage and ligamentous joint
      structures in vivo. DESIGN: An adenoviral vector (AdTGF-beta1(223,225)) was used
      for the overexpression of active TGF-beta1 in knee joints of C57Bl/6 mice.
      RESULTS: It was found that physiological relevant levels of active TGF-beta1
      produced by the synovial lining layer resulted in histopathological changes:
      hyperplasia of synovium and chondro-osteophyte formation at the so-called chondro
      synovial junctions. No histological changes were seen after intra-articular
      injection of an empty control vector (AdDL70-3) or by overexpression of latent
      TGF-beta1 (AdTGF-beta1). The predominant site of TGF-beta production in
      osteoarthritis (OA) and rheumatoid arthritis (RA) is the synovial lining layer.
      To address the question whether the TGF-beta-induced changes were related to the
      expression site in the synovial lining, the synovial lining layer was depleted by
      local treatment with liposomes encapsulating clodronate. Depletion of the lining
      resulted in a dramatic change of TGF-beta1-induced pathology: markedly reduced
      chondro-osteophyte formation and increased accumulation of extracellular matrix
      in the synovium. CONCLUSION: This study shows that overexpression of active TGF
      beta1 in the knee joint results in OA-like changes and suggests the synovial
      lining cells contribute to the chondro-osteophyte formation.

PMID- 11237661
TI  - Acridine orange induces binucleation in chondrocytes.
AB  - OBJECTIVE: Although it is well known that binuclear cells commonly appear among
      the chondrocytes of normal cartilages as well as among neoplastic chondrocytes of
      chondrosarcomas, the mechanism of binucleation is still unclear. Therefore, this
      study was undertaken to clarify the mechanism of binucleation in chondrocytes,
      using primary culture cells of growth plate cartilage. DESIGN: These chondrocytes
      were exposed to acridine orange (AO) which is a fluorescent dye for
      differentiating certain DNAs and RNAs in nuclei and cytoplasm, and which inhibits
      mitosis. After exposure to 0.5 microg/ml AO, for 0, 6, 24, 48, and 96 h, the
      following parameters were investigated: (1) cell growth rate (GR); (2) frequency
      of hyperdiploid cells (%HDC) by DNA cytofluorometry; (3) mitotic index (MI); (4)
      BrdU labeling index (LI); (5) frequency of binuclear cells (%BNC). RESULTS:
      Compared with the control cells, which were cultured in AO-free medium, the GR
      was remarkably inhibited at 24 h. MI was also decreased from 6 to 24 h, and LI
      decreased at 48 h. However, these parameters were recovered at 96 h. The %HDC was
      increased from 6 to 96 h, and the %BNC was also increased to a maximum of six
      times that of the control cells at 96 h. DISCUSSION: These results suggested that
      the binuclear cells observed among the cultured chondrocytes may be formed from
      G2 arrested cells by amitotic nuclear division, but not by mitosis without
      cytoplasmic division or cell fusion.

PMID- 11237662
TI  - More knee joint osteoarthritis (OA) in mice after inactivation of one allele of
      type II procollagen gene but less OA after lifelong voluntary wheel running
      exercise.
AB  - OBJECTIVE: To investigate the incidence and severity of osteoarthritis (OA) and
      the effects of voluntary wheel running in normal mice and mice carrying either a
      targeted inactivation of one allele, heterozygous 'knockout', of Col2a1 gene or
      both alleles, homozygous 'knockout', of Col11a2 gene. METHODS: Mice lived until
      15 months of age in individual cages. Running activity was recorded around the
      clock. OA changes were evaluated from serial knee joint sections by light
      microscopy. RESULTS: Heterozygous inactivation of Col2a1 gene coding for type II
      procollagen made the cartilage more susceptible to OA. At 15 months of age, OA
      prevalence was 60-90% in knockouts and 20-45% in normal controls (P < 0.01
      0.001). Unexpectedly, a reduction of OA due to wheel running was observed in both
      knockout strains (P< 0.05-0.01). This effect was most evident in the femoral
      condyles. Incidence of OA in runners was approximately 50-85% of that in
      sedentary littermates. OA prevalence was higher in normal control and runner mice
      with high body weight. Running did not affect OA development in normal mice.
      CONCLUSION: Heterozygous knockout of Col2a1 gene increased the OA prevalence in
      mice. Lifelong voluntary wheel running had a protective effect against OA in both
      knockout mice lines. The reason for this remains unknown. Reduction of OA may
      result from the reorganization and strengthening of the articular cartilage
      collagen network and/or adjacent muscles due to running, or lower body weight.
      Increased compliance of the articular cartilage and bones of the knockout mice
      may also contribute to the reduction of OA in exercised animals.

PMID- 11237663
TI  - Hyaluronan does not affect cytokine and chemokine expression in osteoarthritic
      chondrocytes and synoviocytes.
AB  - OBJECTIVE: Many studies have evidenced the clinical efficacy of hyaluronan (HA)
      in the treatment of osteoarthritis (OA). However, human and animal studies have
      described proinflammatory effects of HA on cells not involved in OA. We therefore
      investigated whether different molecular weight HA preparations can affect
      proinflammatory cytokine (IL1beta and TNFalpha) or chemokine (IL8, MCP-1 and
      RANTES) expression in human chondrocytes and synoviocytes isolated from OA
      patients. DESIGN: Human chondrocytes and synoviocytes were cultured in vitro in
      the presence or absence of three different purified HA pharmaceutical
      preparations (1x10(6) Kd, 5x10(5) Kd and 6.5x10(4) Kd) and assessed for the
      production of proinflammatory cytokines and chemokines and their mRNA expression.
      RESULTS: basal conditions, both chondrocytes and synoviocytes produce only MCP-1
      and IL8, along with low quantities of IL1beta and TNFalpha, but not RANTES. IL8
      production was generally about 100 times higher in chondrocytes than in
      synoviocytes, while MCP-1 was roughly twice as high in synoviocytes than in
      chondrocytes. At the mRNA level, expression of IL1beta, TNFalpha, IL8, MCP-1 and
      RANTES did not change in the presence of the three HA preparations either in
      synoviocytes or in chondrocytes with respect to basal condition. None of the
      three different HA preparations significantly affected production of IL8 or MCP
      1. CONCLUSIONS: These data demonstrate that preparations of HA of the same origin
      but with different MWs do not induce proinflammatory cytokines and chemokines
      expressed by chondrocytes and synoviocytes that are either directly or indirectly
      involved in OA progression.

PMID- 11237665
TI  - Assessment of rat articular cartilage maturation using 50-MHz quantitative
      ultrasonography.
AB  - OBJECTIVE: The objective was to assess the relationship between maturation
      related structural changes of articular cartilage and variations of acoustic
      parameters estimated using high frequency ultrasonography. DESIGN: Patellae taken
      from 48 immature Wistar male rats and divided into six age groups (from five to
      11 weeks old) were explored in vitro using 50-MHz scanning acoustic microscopy,
      then assessed by histology for the analysis of the cartilage cell distribution
      and fibrillar collagen organization. The variation of cartilage proteoglycan and
      collagen content with age was evaluated. Thickness measurements performed on both
      B-scan images and histologic sections were compared. Ultrasonic radiofrequency
      signals reflected by the cartilage surface and backscattered from its internal
      matrix were processed to estimate the integrated reflection coefficient (IRC) and
      apparent integrated backscatter (AIB). RESULTS: One-way ANOVA indicated that
      acoustic parameters and thickness change significantly (P < 0.05) as the animal
      matures because of age-related changes in cartilage composition and morphology. A
      moderate correlation was found between IRC and the animal age. The parameter
      decreased slightly but significantly over time. However, a good correlation was
      observed between the rat age and the AIB, which decreased significantly over
      time. The parameter variation was mostly related to the changes in collagen fiber
      orientation, and/or to a change in cell size, density and organization.
      CONCLUSIONS: Current results indicate that acoustic properties of cartilage are
      affected by maturation-related cartilage changes. This suggests that high
      frequency ultrasonography may serve as a useful means for the investigation of
      cartilage matrix structural changes occurring under various clinical
      circumstances, like those observed during osteoarthritis, and for the evaluation
      of the efficacy of specific therapeutics.

PMID- 11237666
TI  - Re: 'Neochondrogenesis in repair of full-thickness articular cartilage defects
      using free autogenous periosteal grafts in the rabbit. A follow-up in six months'
      by Carranza-Bencano et al.

PMID- 11237664
TI  - Characterization of a biomaterial with cartilage-like properties expressing type
      X collagen generated in vitro using neonatal porcine articular and growth plate
      chondrocytes.
AB  - OBJECTIVE: The availability of cartilage with or without the potential to ossify
      and suitable for surgical restoration and resurfacing of joints is an important
      clinical problem in arthritis-related pathology, trauma and reconstructive
      surgery. Here, we designed experiments to generate a biomaterial with cartilage
      like properties by culturing neonatal porcine articular and growth plate
      chondrocytes on a hydrogel substrate and to examine the biochemical and
      histological characteristics of the resulting tissue. DESIGN: Neonatal porcine
      epiphyseal and growth plate chondrocytes were cultured on poly(2-hydroxyethyl
      methacrylate) (polyHEMA)-coated dishes to prevent their adherence to plastic. We
      previously described that this procedure allows the maintenance of the
      chondrocyte-specific phenotype for > or = 8 months. Chondrocytes were isolated by
      successive enzymatic digestions and cultured at high density (>2.0 x 10(7)
      cells/ml) in DMEM with 10% FBS, 50 microg/ml ascorbic acid, glutamine, vitamins,
      and antibiotics for up to 10 weeks on 60 mm plastic culture dishes coated with
      polyHEMA. The tissues produced during culture were studied histologically and
      biochemically and were examined for cellular proliferation employing(3)H
      thymidine incorporation and for their collagen production employing biosynthetic
      labeling with(14)C-proline and Western blot with specific antibodies. The
      expression of relevant collagen genes was examined employing RT-PCR. RESULTS:
      Within 24 h of culture, isolated chondrocytes organized into well-formed clusters
      and in 2 weeks formed structures with gross appearance and consistency similar to
      those of natural cartilage. The wet weight of the tissue formed in vitro
      increased six-fold during the 10-week period of study. Cell proliferation
      measured by the incorporation of(3)H-thymidine increased during the first 3 weeks
      and reached a plateau in subsequent weeks. Histological examination showed that
      the cultures contained rounded chondrocytes embedded in an abundant cartilaginous
      extracellular matrix. The cartilage formed contained large amounts of collagen
      and sulfated proteoglycans as examined by staining with Masson's Trichrome and
      Alcian blue, respectively. Deposition of calcium in the deeper layers of the
      tissue was demonstrated with the von Kossa stain. Western analyses with specific
      antibodies showed that type II collagen was present from the first week and
      progressively increased in the cultures, whereas type X collagen was first
      detected at 4 weeks and increased with length of culture. When chondrocytes
      isolated from the growth plate were included, small amounts of type I collagen
      were detected in the medium of cultured biomaterial as expected. Type III
      collagen was not detected by Western blot over the 10-week period. High levels of
      type II and type X collagen gene expression were demonstrated by RT-PCR.
      CONCLUSION: These studies demonstrate the production in vitro of cartilage-like
      tissue with similar morphological, histochemical and biochemical characteristics
      to those of natural growth plate cartilage. The cartilage generated in vitro has
      the potential to be used in reconstructive surgery and in joint resurfacing and
      restoration of skeletal defects.

PMID- 11237668
TI  - Specific, substantial, and credible.

PMID- 11237669
TI  - Rhesus monkey model for fetal gene transfer: studies with retroviral- based
      vector systems.
AB  - Many life-threatening conditions that can be diagnosed early in gestation may be
      treatable in utero using gene therapy. In order to determine in utero gene
      transfer efficiency and safety, studies were conducted with fetal rhesus monkeys
      as a model for the human. Included in these studies were Moloney murine leukemia
      virus (MLV)-based amphotropic retrovirus, vesicular stomatitis virus-G (VSV-G)
      pseudotyped MLV, and a VSV-G pseudotyped HIV-1-based vector, all expressing the
      enhanced green fluorescent protein (EGFP) as a reporter gene and driven by a
      cytomegalovirus-immediate early promoter (N = 16). Rhesus monkey fetuses were
      administered viral vector supernatant preparations by the intraperitoneal (ip) (N
      = 14) or intrahepatic (ih) (N = 2) routes via ultrasound guidance at 55 +/- 5
      days gestation (late first trimester; term 165 +/- 10 days). Fetuses were
      monitored sonographically, specimens were collected prenatally and postnatally,
      and tissue harvests were performed at birth or 3 or 6 months postnatal age (3-10
      months post-gene transfer). PCR analyses demonstrated that transduced cells were
      present at approximately 1.2% in peripheral blood mononuclear cells from fetuses
      administered amphotropic MLV, <0.5% in fetuses receiving MLV/VSV-G, and
      approximately 4.2% for the lentiviral vector, which decreased to 2% at birth.
      Hematopoietic progenitors showed that overall (mean of all time points assessed),
      approximately 25% of the collected colonies were positive for the EGFP transgene
      with the lentiviral vector, which was significantly greater than results achieved
      with the MLV-based vector systems (4-9%; P < or = 0.001-0.016). At necropsy,
      0.001-10% of the total genomic DNA was positive for EGFP in most tissues for all
      groups. EGFP-positive fluorescent cells were found in cell suspensions of thymus,
      liver, spleen, lymph nodes, cerebral cortex, and bone marrow (0.5-6%). Overall,
      the results of these studies have shown: (1) healthy infants expressing vector
      sequences up to 10 months post-gene transfer, (2) fetal primate administration of
      retroviral vectors results in gene transfer to multiple organ systems, (3) the
      highest level of gene transfer to hematopoietic progenitors was observed with the
      lentiviral vector system, and (4) there was no evidence of transplacental
      transfer of vector sequences into the dams. The rhesus monkey is an important
      preclinical primate model system for exploring gene transfer approaches for
      future applications in humans.

PMID- 11237670
TI  - Engraftment of genetically engineered amniotic epithelial cells corrects
      lysosomal storage in multiple areas of the brain in mucopolysaccharidosis type
      VII mice.
AB  - Cell-mediated gene therapy for visceral lesions of lysosomal storage diseases is
      promising; however, the treatment of central nervous system (CNS) lesions remains
      a challenge. In this study, we generated rat amniotic epithelial cells (AEC) that
      overexpress and secrete human beta-glucuronidase (GUSB) following transduction
      with an adenoviral vector encoding human GUSB. The AEC were used as donor cells
      for cell-mediated gene therapy of CNS lesions in mice with mucopolysaccharidosis
      type VII (MPSVII), a lysosomal storage disorder caused by an inherited deficiency
      of GUSB activity. After confirmation that the secreted GUSB was taken up mainly
      via mannose 6-phosphate receptors in primary cultured neurons, the AEC were
      transplanted into the brains of adult MPSVII mice. Histochemical analysis showed
      extensive GUSB activity throughout the ipsilateral hemisphere of the recipient
      brains, and pathological improvement of the lysosomal storage was observed even
      in regions far from the site of injection. These results suggest that
      intracerebral transplantation of genetically engineered AEC has therapeutic
      potential for the treatment of CNS lesions in lysosomal storage disorders.

PMID- 11237671
TI  - Conditional abatement of tissue fibrosis using nucleoside analogs to selectively
      corrupt DNA replication in transgenic fibroblasts.
AB  - Progressive tissue fibrosis can compromise epithelial function resulting in organ
      failure. Appreciating evidence suggests that fibroblasts provide fibrogenic
      collagens during such injury. We further tested this notion by attempting to
      reduce the physiologic consequences of organ fibrosis through the selective
      killing of fibroblasts at sites of injury. Here, we report the conditional
      reduction of tissue fibroblasts using the coding sequence for herpesvirus
      thymidine kinase (DeltaTK) put under the control of a cell-specific promoter from
      the gene encoding fibroblast-specific protein 1 (FSP1). Transgenic fibroblasts
      from mice carrying FSP1.DeltaTK minigenes expressed thymidine kinase concordantly
      with native FSP1 and, compared to transgenic epithelium, were selectively
      susceptible to the lethal effects of nucleoside analogs either in culture or
      during experimental renal fibrosis. The numbers of fibroblasts in fibrogenic
      kidney tissue were reduced on exposure to nucleoside analogs as was the degree of
      type I collagen deposition and the extent of fibrosis. Fibroblast reduction
      following the stress of DNA chain termination highlights the important
      contribution of cell division during fibrogenesis. Our findings convey a proof of
      principle regarding the importance of FSP1(+) fibroblasts in fibrosis as well as
      providing a new approach to treating the relentless scarification of tissue.

PMID- 11237672
TI  - Development of a syngenic murine B16 cell line-derived melanoma susceptible to
      destruction by neuroattenuated HSV-1.
AB  - HSV-1 ICP34.5 mutants can slow progression of preformed tumors in rodent models.
      However, the current models available for study are limited due to the lack of a
      syngenic, low-immunogenic tumor model susceptible to HSV-1. Thus we have
      developed a new model to determine the role of the immune response in viral
      mediated tumor destruction. The human herpesvirus entry (Hve) receptors (HveA,
      HveB, and HveC) and a control plasmid were transfected into B78H1 murine melanoma
      cells. Transfection of HveA and HveC conferred sensitivity to HSV-1 to these
      cells. A10 (HveA), C10 (HveC), and control cells were able to form tumors
      reproducibly in vivo. The transfection of the receptors into B78H1 cells did not
      induce a detectable in vivo immunogenicity to the tumors. Finally, A10 and C10
      tumor-bearing mice treated with HSV-1 1716 had significant prolongation of
      survival compared to mock-treated mice. These data suggest that A10 and C10 will
      be useful as in vivo models for studying the role of the immune response in viral
      mediated tumor destruction.

PMID- 11237673
TI  - Specific down-regulation of HER-2/neu mediated by a chimeric U6 hammerhead
      ribozyme results in growth inhibition of human ovarian carcinoma.
AB  - The U6 expression system was explored for efficient expression of a ribozyme
      against the human proto-oncogene c-neu. A hammerhead ribozyme (neuRz) and the
      control mutant ribozyme (MRz) were targeted to cleave c-neu mRNA at the tyrosine
      kinase domain. In vitro cleavage showed that neuRz was very active while MRz was
      not. Near-maximal target cleavage observed at a low ribozyme:target ratio (0.1)
      suggests that neuRz has good activity and turnover capability under physiological
      conditions, i.e., <5 mM MgCl(2) and 37 degrees C. Chimeric U6 ribozyme was
      expressed at about 5 x 10(6) copies/cell at 48 h in the ovarian carcinoma cell
      line SKOV-3.ip1. Partial down-regulation of c-neu mRNA and protein was observed
      in a dose-dependent manner in cells transiently transfected with U6neuRz- but not
      with MRz-containing plasmid. Sorted transient transfectants demonstrated dramatic
      growth inhibition with the neuRz-expressing cells. Our results demonstrate that
      the U6 expression system is very efficient and suitable for the expression of a
      hammerhead ribozyme. Moreover, nonviral delivery of the neuRz-expressing plasmid
      resulted in specific down-regulation of c-neu and, subsequently, growth
      inhibition of ovarian cancer cells overexpressing c-neu.

PMID- 11237674
TI  - Targeted correction of a defective selectable marker gene in human epithelial
      cells by small DNA fragments.
AB  - A novel gene targeting strategy, small fragment homologous replacement (SFHR),
      has been used to correct specific genomic lesions in human epithelial cells. The
      frequency of targeting was estimated to be 1-10%. However, given the genomic
      target, the cystic fibrosis transmembrane conductance regulator (CFTR) gene, it
      is difficult to accurately quantify targeting frequency. As an alternative to
      targeting CFTR, targeted correction of a mutant selectable marker or reporter
      gene would be more amenable to accurate and rapid quantification of gene
      targeting efficiency. The present study evaluates the conditions that modulate
      SFHR-mediated correction of a defective Zeocin antibiotic resistance (Zeo(r))
      gene that has been inactivated by a 4-bp insertion. The conditions include
      delivery systems, plasmid-to-fragment ratio, fragment length, and fragment
      strandedness (single- or double-stranded DNA). Targeting fragments comprise the
      wild-type Zeo(r) gene sequence and were either 410 (Zeo1) or 458 bp (Zeo3).
      Expression vectors containing the corrected Zeo(r) gene were isolated as episomal
      plasmids or were allowed to stably integrate into cultured human airway
      epithelial cells. Correction of the Zeo(r) gene was phenotypically defined as
      restoration of resistance to Zeocin in either bacteria or epithelial cell clones.
      Extrachromosomal gene correction was assayed using polymerase chain reaction
      amplification, restriction enzyme digestion, DNA sequencing, and Southern blot
      hybridization analysis of DNA from isolated prokaryotic and eukaryotic clones.
      Neither random sequence alteration in the target episomal gene nor random
      integration of the small fragments was detected. Targeted correction efficiencies
      of up to 4% were attained. These studies provide insight into parameters that can
      be modulated for the optimization of SFHR-mediated targeting.

PMID- 11237676
TI  - Adenoviral delivery of osteoprotegerin ameliorates bone resorption in a mouse
      ovariectomy model of osteoporosis.
AB  - Osteoprotegerin (OPG) regulates bone resorption by inhibiting osteoclast
      formation, function, and survival. The current studies employed a mouse
      ovariectomy (OVX) model of estrogen deficiency to investigate gene therapy with
      OPG as a means of preventing osteoporosis. Young adult females injected with a
      recombinant adenoviral (Ad) vector carrying cDNA of either full-length OPG or a
      fusion protein combining the hOPG ligand-binding domain with the human
      immunoglobulin constant domain (Ad-hOPG-Fc) developed serum OPG concentrations
      exceeding the threshold needed for efficacy. However, elevated circulating OPG
      levels were sustained for up to 18 months only in mice given Ad-hOPG-Fc.
      Administration of Ad-hOPG-Fc titers between 10(7) and 10(9) pfu yielded dose
      dependent increases in serum OPG. Mice subjected to OVX or sham surgery followed
      by immediate treatment with Ad-hOPG-Fc had significantly more bone volume with
      reduced osteoclast numbers in axial and appendicular bones after 4 weeks. In
      contrast, animals given OVX and either a control vector or vehicle had
      significantly less bone than did comparably treated sham-operated mice. This
      study demonstrates that a single adenoviral gene transfer can produce persistent
      high-level OPG expression and shows that gene therapy to provide sustained
      delivery of OPG may prove useful in treating osteoporosis.

PMID- 11237675
TI  - Combination angiostatin and endostatin gene transfer induces synergistic
      antiangiogenic activity in vitro and antitumor efficacy in leukemia and solid
      tumors in mice.
AB  - Angiostatin and endostatin are potent endothelial cell growth inhibitors that
      have been shown to inhibit angiogenesis in vivo and tumor growth in mice.
      However, tumor shrinkage requires chronic delivery of large doses of these
      proteins. Here we report synergistic antitumor activity and survival of animals
      when these factors are delivered in combination to tumors by retroviral gene
      transfer. We have demonstrated this efficacy in both murine leukemia and melanoma
      models. Complete loss of tumorigenicity was seen in 40% of the animals receiving
      tumors transduced by the combination of angiostatin and endostatin in the
      leukemia model. The synergy was also demonstrated in vitro on human umbilical
      vein endothelial cell differentiation and this antiangiogenic activity may
      suggest a mechanism for the antitumor activity in vivo. These findings imply
      separate pathways by which angiostatin and endostatin mediate their
      antiangiogenic effects. Together, these data suggest that a combination of
      antiangiogenic factors delivered by retroviral gene transfer may produce
      synergistic antitumor effects in both leukemia and solid tumors, thus avoiding
      long-term administration of recombinant proteins. The data also suggest that
      novel combinations of antiangiogenic factors delivered into tumors require
      further investigation as therapeutic modalities.

PMID- 11237677
TI  - Host responses and persistence of vector genome following intrabronchial
      administration of an E1(-)E3(-) adenovirus gene transfer vector to normal
      individuals.
AB  - Adenovirus (Ad)-mediated gene transfer to the respiratory epithelium of
      experimental animals and to nasal and airway epithelium of individuals with
      cystic fibrosis is followed by transient gene expression. Extensive studies in
      experimental animals are consistent with the concept that local cellular host
      anti-vector immune responses account for this short-term expression, and systemic
      and local [lung epithelial lining fluid (ELF)] anti-Ad neutralizing antibodies
      are generated following Ad vector administration to the respiratory epithelial
      surface. To determine if this paradigm holds in normal humans, a first-generation
      Ad vector (Ad(GV)CD.10, an E1(-)E3(-) Ad serotype 5-based vector coding for the
      Escherichia coli cytosine deaminase gene) was sprayed locally in escalating doses
      (8 x 10(8)-8 x 10(10) particle units (pu), n = 2/group) into the lung airway
      epithelium of six normal individuals. Serum, ELF, and endobronchial biopsies were
      obtained at baseline and at various time points following vector administration.
      In contrast to the observations in experimental animals in which lung
      administration of first-generation Ad vectors is followed by strong systemic and
      local host response, bronchial spray administration of the Ad vector to normal
      humans showed: (1) minimal inflammation in bronchial biopsies, bronchial
      brushing, and bronchoalveolar lavage fluid; (2) no blood lymphocyte proliferation
      in five of six individuals in response to in vitro stimulation with Ad antigens;
      and (3) no significant increase from baseline in blood or lung ELF anti-Ad
      neutralizing antibodies. Despite this minimal normal human anti-Ad host response,
      dose-dependent levels of vector DNA in the airway epithelium were transient.
      Vector DNA in the targeted airway epithelial cells peaked in a dose-dependent
      fashion at 0.007 to 1.1 copies/cell at day 7 and declined thereafter, reducing to
      <10% of peak levels by 2 weeks. These observations demonstrate both the strengths
      and the limits of using experimental animals to predict human responses to gene
      transfer vectors. While the transient nature of Ad vector persistence in the
      airway epithelium is predicted by most experimental animal studies, respiratory
      epithelial administration of first-generation Ad vectors at doses up to 10(10) pu
      to airway epithelium of healthy individuals elicits minimal to no detectable
      systemic and mucosal humoral and cellular immune responses, an observation
      diametrically opposed to the host responses measured in experimental animals.
      These findings suggest that, while adaptive anti-Ad immune responses likely play
      some role in the disappearance of the vector DNA following vector administration
      to the human lung, other mechanisms may also be involved in the response of
      humans to Ad gene transfer vectors.

PMID- 11237678
TI  - Membrane macrophage colony-stimulating factor on MADB106 breast cancer cells does
      not activate cytotoxic macrophages but immunizes rats against breast cancer.
AB  - Weakly immunogenic, but highly malignant, rat MADB106 breast cancer cells were
      retrovirally transduced with the membrane form of macrophage colony-stimulating
      factor (mM-CSF). The cloned mM-CSF-transfected MADB106 cells physically
      conjugated with macrophages, but were not killed by the macrophages in 48-h
      cytotoxicity assays. Macrophages killed the mM-CSF-expressing tumors in the
      presence of noncytotoxic doses of either taxol or taxol plus cisplatin. This
      indicated that macrophages bind to the mM-CSF expressed on the tumor cells, but
      for successful macrophage cytotoxicity to occur against mM-CSF-transduced tumor
      cells other factors must be present. The mM-CSF-transfected tumor cells were
      rejected when inoculated subcutaneously into normal rats. Cloned MADB106 tumor
      cells which expressed high amount of mM-CSF were rejected, while tumor cells that
      displayed lower levels of mM-CSF grew in 60% of the inoculated rats. The mM-CSF
      transfected tumors that grew were smaller and had a greater amount of necrosis,
      compared to the viral vector tumors. Rats that spontaneously rejected the mM-CSF
      transfected MADB106 cells showed rechallenge resistance to unmodified parental
      MADB106 and R3230Ac breast cancers, but not to the F98 glioma. These observations
      suggest that breast cancer-specific immunity was induced by the inoculation of mM
      CSF-expressing MADB106 tumor cells.

PMID- 11237679
TI  - Combined injection of rAAV with mannitol enhances gene expression in the rat
      brain.
AB  - Recombinant adeno-associated viruses (rAAV) are highly efficient vectors for gene
      transfer into the central nervous system (CNS). However, a major hurdle for gene
      delivery to the mammalian brain is to achieve high-level transduction in target
      cells beyond the immediate injection site. Therefore, in addition to improvements
      in expression cassettes and viral titers, optimal injection parameters need to be
      defined. Here, we show that previous studies of somatic cell gene transfer to the
      mammalian brain have used suboptimal injection parameters, with even the lowest
      reported perfusion rates still excessively fast. Moreover, we evaluated the
      effect of local administration of mannitol to further enhance transgene
      expression and vector spread. Ultraslow microperfusion of rAAV, i.e., <33 nl/min,
      resulted in significantly higher gene expression and less injury of surrounding
      tissue than the previously reported rates of 100 nl/min or faster. Co-infusion of
      mannitol facilitated gene transfer to neurons, increasing both the total number
      and the distribution of transduced cells by 200-300%. Gene transfer studies in
      the CNS using rAAV should use very slow infusion rates and combined injection
      with mannitol to maximize transduction efficiency and spread.

PMID- 11237680
TI  - Combined adenovirus-mediated nitroreductase gene delivery and CB1954 treatment: a
      well-tolerated therapy for established solid tumors.
AB  - Gene-directed enzyme prodrug therapy (GDEPT) is a refinement of cancer
      chemotherapy that generates a potent cell-killing drug specifically in tumor
      cells by enzymatic activation of an inert prodrug. We describe in vivo studies
      that evaluate the efficacy and safety of intratumoral (i.t.) injection of an
      adenovirus vector (CTL102) expressing Escherichia coli nitroreductase (NTR)
      combined with systemic prodrug (CB1954) treatment. A single i.t. injection of
      CTL102 (7.5 x 10(9) to -2 x 10(10) particles) followed by CB1954 treatment
      produced clear anti-tumor effects in subcutaneous (s.c.) xenograft models of four
      cancers that are likely candidates for GDEPT (i.e., primary liver, head and neck,
      colorectal and prostate). Virus dose-response studies (s.c. liver model) revealed
      a steep increase and subsequent rapid plateauing of both NTR gene delivery and
      anti-tumor efficacy. Evidence of minor virus spread (toxicity) was observed in a
      s.c. head and neck xenograft model. This was eliminated by passive immunization
      with neutralizing anti-Ad5 antibodies prior to virus injection without reducing
      the magnitude of the anti-tumor effect. Preexisting anti-Ad5 neutralizing
      antibodies may therefore be an advantage rather than an issue in the clinical use
      of this new therapy.

PMID- 11237681
TI  - AAV-mediated delivery of ciliary neurotrophic factor prolongs photoreceptor
      survival in the rhodopsin knockout mouse.
AB  - Retinitis pigmentosa (RP), an inherited retinal degenerative disease causing
      blindness, is characterized by progressive apoptotic death of photoreceptors.
      Therapeutic modification of photoreceptor apoptosis may provide an effective
      therapy for this disorder. Ciliary neurotrophic factor (CNTF) has been shown to
      promote survival of a number of different neuronal cell types, including
      photoreceptors. The present study aimed to test whether adeno-associated virus
      (AAV)-mediated delivery of the gene encoding CNTF delays photoreceptor death in
      the rhodopsin knockout (opsin(-/-)) mouse, an animal model of RP. The vector was
      made to express a secretable form of CNTF in tandem with a marker GFP. Cultured
      293 cells transduced with this virus expressed both CNTF and GFP. The conditioned
      media from such cells supported the survival of chick dorsal root ganglion
      neurons in the same manner as recombinant CNTF. Subretinal administration of this
      virus led to efficient transduction of photoreceptors as indicated by GFP
      fluorescence and CNTF immunostaining. Histologic examination showed significant
      photoreceptor preservation in the injected quadrant of the retina. This
      protection lasted through termination of the experiment (3 months). AAV-mediated
      delivery of CNTF may have implications for the treatment of human retinal
      degeneration.

PMID- 11237682
TI  - Cutaneous transfection and immune responses to intradermal nucleic acid
      vaccination are significantly enhanced by in vivo electropermeabilization.
AB  - Naked DNA injection with electropermeabilization (EP) is a promising method for
      nucleic acid vaccination (NAV) and in vivo gene therapy. Skin is an ideal target
      for NAV due to ease of administration and the accessibility of large numbers of
      antigen-presenting cells within the tissue. This study demonstrates that in vivo
      skin EP may be used to increase transgene expression up to an average of 83-fold
      relative to naked DNA injection (50 microg DNA per dose, P < 0.005). Transfected
      cells were principally located in dermis and included adipocytes, fibroblasts,
      endothelial cells, and numerous mononuclear cells with dendritic processes in a
      porcine model. Transfected cells were also observed in lymph nodes draining
      electropermeabilized sites. A HBV sAg-coding plasmid was used to test skin EP
      mediated NAV in a murine model. Analysis of humoral immune responses including
      immunoglobulin subclass profiles revealed strong enhancement of EP-mediated NAV
      relative to naked DNA injection, with a Th1-dominant, mixed-response pattern
      compared to immunization with HBV sAg protein that was exclusively Th2 (P =
      0.02). Applications for these findings include NAV-based modulation of immune
      responses to pathogens, allergens, and tumor-associated antigens and the
      modification of tolerance.

PMID- 11237683
TI  - Quantitative analysis of transgene protein, mRNA, and vector DNA following
      injection of an adenoviral vector harboring glial cell line-derived neurotrophic
      factor into the primate caudate nucleus.
AB  - Gene therapy for neurodegenerative diseases relies on stable expression of a
      vector-mediated transgene in the human central nervous system (CNS). In nonhuman
      primate CNS, transgene expression has been primarily assessed using descriptive
      histological methods. Here, we quantified the expression of a human glial cell
      line-derived neurotrophic factor (hGDNF) transgene using an ELISA specific for
      hGDNF protein and real-time quantitative RT-PCR and PCR for hGDNF mRNA and vector
      DNA, respectively. Transgene expression was assessed 1 week after injection of an
      E1-, E3-deleted adenovirus harboring hGDNF into the caudate nucleus of St. Kitts
      green monkey. We found that 57-147 million and 116-771 million copies of hGDNF
      mRNA and vector DNA, respectively, were present per 10,000 copies of the beta
      actin gene. In the same sites, 40-152 pg of hGDNF protein per milligram of tissue
      was measured. Comparisons of these measures among monkeys demonstrated variable
      vector DNA and protein levels, but consistent mRNA levels at one-third of the
      level of vector DNA. This suggests that local responses to the vector play a role
      in the level of transgene expression and that high levels of vector DNA do not
      necessarily predict a high level of transgene protein. However, the results of
      this study do show that neuroprotective levels of GDNF transgene expression can
      be achieved following injection of an adenoviral vector into nonhuman primate
      caudate. Moreover, these assays provide quantitative methods for evaluating and
      comparing viral vectors in primate CNS.

PMID- 11237684
TI  - A versatile framework for the design of ligand-dependent, transgene-specific
      transcription factors.
AB  - The ability to regulate transgene expression will be essential for the safety and
      efficacy of many gene therapies. Various ligand-dependent transcription factors,
      including steroid hormone receptors, have been modified to enable transgene
      specific regulation. To minimize effects on cellular gene expression, chimeric
      steroid receptors have been constructed by replacing their native DNA binding
      domain (DBD) with a heterologous DBD, like that from the yeast transcription
      factor GAL4. This approach has limitations for human gene therapy, including the
      potential immunogenicity of the GAL4 domain and the inability to discriminate
      between different GAL4-linked transgenes in the same cell. To address this, we
      have constructed chimeric regulators containing the human estrogen receptor (ER)
      ligand binding domain (LBD) and a Cys(2)-His(2)-type zinc finger DBD. Cys(2)
      His(2) zinc finger domains are common among human DNA binding proteins and can be
      engineered to selectively bind different DNA sequences. We demonstrate over 500
      fold drug-dependent transgene induction with these chimeric regulators in vitro
      and the ability to regulate an adenovirus-delivered transgene in mice. Two
      chimeras containing different Cys(2)-His(2) domains displayed highly sequence
      specific binding and regulation. Incorporating a point mutation in the ER LBD
      that ablates estrogen binding enables selective in vivo regulation with the
      clinically useful anti-estrogen tamoxifen. These Cys(2)-His(2)-ER LBD chimeras
      represent a versatile framework for creating transgene-specific regulators
      potentially useful for human gene therapy applications.

PMID- 11237685
TI  - Primate in utero gene transfer comes of age.

PMID- 11237686
TI  - Expression and characterization of human recombinant and alpha-N
      acetylglucosaminidase.
AB  - Mucopolysaccharidosis type IIIB (MPS-IIIB, Sanfilippo type B Syndrome) is a
      heterosomal, recessive lysosomal storage disorder resulting from a deficiency of
      [alpha]-N-acetylglucosaminidase (NAGLU). To characterize this enzyme further and
      evaluate its potential for enzyme replacement studies we expressed the NAGLU
      encoding cDNA in Chinese hamster ovary cells (CHO-K1 cells) and purified the
      recombinant enzyme from the medium of stably transfected cells by a two-step
      affinity chromatography. Two isoforms of recombinant NAGLU with apparent
      molecular weights of 89 and 79 kDa were purified and shown to differ in their
      glycosylation pattern. The catalytic parameters of both forms of the recombinant
      enzyme were indistinguishable from each other and similar to those of NAGLU
      purified from various tissues. However, compared to other recombinant lysosomal
      enzymes expressed from CHO-K1 cells, the mannose-6-phosphate receptor mediated
      uptake of the secreted form of recombinant NAGLU into cultured skin fibroblasts
      was considerably reduced. A small amount of phosphorylated NAGLU present in
      purified enzyme preparations was shown to be endocytosed by MPS-IIIB fibroblasts
      via the mannose-6-phosphate receptor-mediated pathway and transported to the
      lysosomes, where they corrected the storage phenotype. Direct metabolic labeling
      experiments with Na(2) (32)PO(4) confirmed that the specific phosphorylation of
      recombinant NAGLU secreted from transfected CHO cells is significantly lower when
      compared with a control lysosomal enzyme. These results suggest that the use of
      secreted NAGLU in future enzyme and gene replacement therapy protocols will be
      severely limited due to its small degree of mannose-6-phosphorylation.

PMID- 11237687
TI  - Expression of recombinant zeta-crystallin in Escherichia coli with the help of
      GroEL/ES and its purification.
AB  - zeta-Crystallin is a taxon-specific crystallin found in the eye lens of guinea
      pig and other hystricomorph rodents and camelids. It is an NADPH:quinone
      oxidoreductase and is also present in low amounts in other tissues where it might
      act as a detoxifying enzyme. A lens-specific promoter confers lens-specific
      expression of the gene in high amounts where it is speculated to play a
      structural role in maintaining the transparency of the lens ensemble. A deletion
      mutation leads to autosomal dominant congenital cataract and also results in the
      loss of NADPH binding. In order to perform structural studies with the protein
      with an aim to delineate the cause of cataract in these mutant guinea pigs,
      recombinant zeta-crystallin was cloned and expressed in Escherichia coli. The
      overexpression of the protein in E. coli resulted in a major fraction of it
      partitioning into inclusion bodies. The co-overexpression of the bacterial
      chaperone system GroEL/ES along with zeta-crystallin could significantly enhance
      the yield of soluble protein. Active zeta-crystallin could then be purified from
      the E. coli using Mono Q anion exchange FPLC and was found to be identical to the
      native zeta-crystallin isolated from the guinea pig lens with respect to size,
      spectral properties, and activity.

PMID- 11237688
TI  - Cloning, expression, purification, and characterization of rat MMP-12.
AB  - Macrophage metalloelastase (MMP-12) is implicated in the pathology of many
      diseases such as emphysema, aortic lesions and cancer. Recently, MMP-12 was
      cloned and purified from mouse and human macrophages. We report here the
      expression of the full-length and catalytic domain of rat MMP-12 in Escherichia
      coli and characterization of the purified enzyme. Inclusion bodies of expressed
      rat MMP-12 catalytic domain were denatured and refolded using a new method, and
      then affinity purified to near homogeneity with zinc-chelating Sepharose. The
      purified rat MMP-12 catalytic domain was highly active in digesting substrates,
      having a K(m) of 12 microM and optimal pH of 7.5--8.5. During investigation of
      natural substrate specificity, we found that rat MMP-12 catalytic domain was able
      to completely degrade collagen-V, partially degrade collagen-I, but it was unable
      to digest collagen-IV. The enzyme could also degrade osteonectin, vitronectin,
      and fibronectin, but not laminin and albumin. The catalytic properties and
      natural substrate specificity of rat MMP-12 catalytic domain differed from those
      of human MMP-12 catalytic domain.

PMID- 11237690
TI  - Purification and some properties of human placental glucose-6-phosphate
      dehydrogenase.
AB  - Glucose-6-phosphate dehydrogenase was purified from human placenta using DEAE
      Sepharose fast flow, 2',5'-ADP Sepharose 4B column chromatography, and
      chromatofocusing on PBE 94 with PB 74. The enzyme was purified with 62% yield and
      had a specific activity of 87 units per milligram protein. The pH optimum was
      determined to be 7.8, using zero buffer extrapolation method. The purified
      placental glucose-6-phosphate dehydrogenase gave two activity bands on native
      PAGE: one band, constituting about 3--5% of total activity, moved slower than the
      remaining 95%. Among the activity bands only the faster moving band gave a band
      on protein staining. The slower moving band, which probably corresponded to the
      higher polymeric form of the G6PD with high specific activity, was not seen on
      native PAGE due to insufficient protein for Coomassie brilliant blue staining.
      The observation of one band on SDS--PAGE with an M(r) of 54 kDa and a specific
      activity lower than expected, suggests the presence of both forms of the G6PD,
      the high polymeric form at low concentration and the inactive form at high
      concentration, in our preparation. Measuring the activities of placental glucose
      6-phosphate dehydrogenase between 20 and 50 degrees C, the activation energy,
      activation enthalpy, and Q(10) were calculated to be 8.16 kcal/mol, 7.55
      kcal/mol, and 1.57, respectively. It was found that human placental G6PD obeys
      Michaelis-Menten kinetics. K(m) values were determined using the concentration
      ranges of 20--300 microM for G6P and 10--200 microM for NADP(+). The K(m) value
      for G6P was 40 microM; the K(m) value NADP(+) was found to be 20 microM. Double
      reciprocal plots of 1/Vm vs 1/G6P (at constant [NADP(+)]) and of 1/Vm vs
      1/NADP(+) (at constant [G6P]) intersected at the same point on the 1/V(m) axis to
      give V(m) = 87 U/mg protein.

PMID- 11237689
TI  - Expression and glycosylation studies of human FGF receptor 4.
AB  - Fibroblast growth factor receptor subtype 4 (FGFR4) has been shown to have
      special activation properties and just one splicing form, unlike the other FGFRs.
      FGFR4 overexpression is correlated with breast cancer and therefore FGFR4 is a
      target for drug design. Our aim is to overexpress high amounts of homogeneous
      FGFR4 extracellular domain (FGFR4(ed)) for structural studies. We show that
      baculovirus-insect cell-expressed FGFR4(ed) is glycosylated on three (N88, N234,
      and N266) of the six possible N-glycosylation sites but is not O-glycosylated.
      The deglycosylated triple mutant was expressed and had binding properties similar
      to those of glycosylated FGFR4(ed), but was still heterogeneous. Large amounts of
      FGFR4(ed) have been produced into inclusion bodies in Escherichia coli and
      refolded at least partly correctly but the refolded E. coli-produced FGFR4(ed)
      still aggregates.

PMID- 11237691
TI  - Molecular cloning, expression, purification, and characterization of fructose-1,6
      bisphosphate aldolase from Thermus aquaticus.
AB  - Fructose-1,6-bisphosphate aldolase from the thermophilic eubacteria, Thermus
      aquaticus YT-1, was cloned and sequenced. Nucleotide-sequence analysis revealed
      an open reading frame coding for a 33-kDa protein of 305 amino acids having amino
      acid sequence typical of thermophilic adaptation. Multiple sequence alignment
      classifies the enzyme as a class II B aldolase that shares similarity with
      aldolases from other extremophiles: Thermotoga maritima, Aquifex aeolicus, and
      Helicobacter pylori (49--54% identity, 76--81% homology). Taq FBP aldolase was
      overexpressed under tac promoter control in Escherichia coli and purified to
      homogeneity using heat treatment followed by two chromatographic steps. Yields of
      40--50 mg of monodisperse protein were obtained per liter of culture. The
      quaternary structure is that of a homotetramer stabilized by an apparent 21-amino
      acid insertion sequence. The recombinant protein is thermostable for at least 45
      min at 80 degrees C with little residual activity below 60 degrees C. Kinetic
      characterization at 70 degrees C, the optimal growth temperature for T.
      aquaticus, indicates extreme negative subunit cooperativity (h = 0.32) with a
      limiting K(m) of 305 microM. The maximal specific activity (V(max)) is 46 U/mg at
      70 degrees C.

PMID- 11237692
TI  - Overexpression and purification of the membrane-bound cytochrome P450 2B4.
AB  - Expression of the membrane-bound cytochrome P450 2B4 by the pLW01-P450 expression
      vector, which utilizes a T7 promoter, is markedly improved by employing
      Escherichia coli strain C41(DE3) [Miroux, B., and Walker, J. (1996) J. Mol. Biol
      260, 289--298; Bridges, A., Gruenke, L., Chang, Y.-T., Vasker, I., Loew, G., and
      Waskell, L. (1998) J. Biol. Chem. 273, 17036--17049]. Using this expression
      system, it was possible to routinely obtain an average of 50--60 mg and as high
      as 100 mg of cyt P450 2B4 per liter of cell culture in volumes of 500 ml. An
      improved purification procedure for cyt P450 2B4 is also described which allows
      recovery of 30% of the expressed protein. It was possible in one step using B-PER
      reagent and polyoxyethylene-9-lauryl ether to both lyse the E. coli and
      solubilize the expressed cyt P450. Cyt P450 2B4 with a specific content of 17
      nmol/mg protein and a single band on polyacrylamide gel electrophoresis was
      routinely isolated. The yield of cyt P450 from the improved purification
      procedure is twice that from the original procedure and the purity of the
      recovered protein typically has a specific content of 17 nmol cyt P450/mg of
      protein.

PMID- 11237693
TI  - Purification of phospholipase D from Dacus carota by three-phase partitioning and
      its characterization.
AB  - Phospholipase D from Dacus carota (carrot) was purified by subjecting it to three
      phase partitioning. The single step of three phase partitioning led to 13-fold
      purification with an activity recovery of 72%. SDS-PAGE analysis showed a single
      band with minimum molecular weight corresponding to nearly 60 kDa. The purified
      enzyme had a pH optimum in the range of 6.0--6.5 and was unstable above 30
      degrees C. Kinetic studies showed a K(m) value of 9.5 mM and a V(max) of 0.35 mL
      min(-1). The enzyme purified by three-phase partitioning was found to resolve
      into two isoenzymes on a DEAE-cellulose column.

PMID- 11237694
TI  - Expression, purification, and characterization of the active immunoglobulin-like
      domain of human granulocyte-colony-stimulating factor receptor in Escherichia
      coli.
AB  - We succeeded in the expression, purification, and refolding of the immunoglobulin
      like (Ig) domain of human granulocyte-colony-stimulating factor (G-CSF) receptor
      with amino-terminal His-tag in Escherichia coli. The refolded Ig domain bound to
      a G-CSF affinity column and could be eluted with free G-CSF as a receptor-ligand
      complex, demonstrating that the Ig domain has the information necessary for
      binding its ligand, G-CSF. The eluted His-Ig/G-CSF complex could be separated
      from excess G-CSF by Ni-NTA column chromatography. The yield of this active
      recombinant His-Ig protein is about 0.72 mg per liter of culture. Its small size
      and the ease of production make this receptor fragment a useful reagent for the
      structural analysis of its complex with G-CSF.

PMID- 11237695
TI  - Escherichia coli FtsH (HflB) degrades a membrane-associated TolAI-II-beta
      lactamase fusion protein under highly denaturing conditions.
AB  - TolAI--II--beta-lactamase, a fusion protein consisting of the inner membrane and
      transperiplasmic domains of TolA followed by TEM--beta-lactamase associated with
      the inner membrane but remained confined to the cytoplasm when expressed at high
      level in Escherichia coli. Although the fusion protein was resistant to
      proteolysis in vivo, it was hydrolyzed during preparative SDS-polyacrylamide
      electrophoresis and when insoluble cellular fractions unfolded with 5 M urea were
      subjected to microdialysis. Inhibitor profiling studies revealed that both a
      metallo- and serine protease were involved in TolAI--II--beta-lactamase
      degradation under denaturing conditions. The in vitro degradation rates of the
      fusion protein were not affected when insoluble fractions were harvested from a
      strain lacking protease IV, but were significantly reduced when microdialysis
      experiments were conducted with material isolated from an isogenic ftsH1 mutant.
      Adenine nucleotides were not required for degradation, and ATP supplementation
      did not accelerate the apparent rate of TolAI--II--beta-lactamase hydrolysis
      under denaturing conditions. Our results indicate that the metalloprotease active
      site of FtsH remains functional in the presence of 3--5 M urea and suggest that
      the ATPase and proteolytic activities of FtsH can be uncoupled if the substrate
      is sufficiently unstructured. Thus, a key role of the FtsH AAA module appears to
      be the net unfolding of bound substrates so that they can be efficiently engaged
      by the protease active site.

PMID- 11237696
TI  - Purification of eukaryotic MutL homologs from Saccharomyces cerevisiae using self
      affinity technology.
AB  - Self-cleaving affinity technology is an effective tool for rapid purification of
      native sequence recombinant proteins overproduced in Escherichia coli. In this
      report, we describe the adaptation of this technology to purify DNA mismatch
      repair proteins overproduced in the eukaryote Saccharomyces cerevisiae. Mlh1 and
      Pms1 are homologs of the E. coli MutL protein that participate in a variety of
      DNA transactions in cells, including correction of DNA replication errors,
      recombination, excision repair, and checkpoint control. Difficulties in preparing
      substantial quantities of highly purified MutL homologs have impeded descriptions
      of their biophysical and biochemical properties and mechanisms of action. To
      overcome this limitation, here we use self-cleaving affinity technology to purify
      to apparent homogeneity the yeast Mlh1--Pms1 heterodimer and the individual yeast
      and human Mlh1 subunit. The availability of these proteins should accelerate an
      understanding of their multiple functions in mismatch repair and other DNA
      transactions. The general approach is a valid alternative for simple, rapid
      purification of recombinant proteins in yeast when expression in bacteria is
      unsuitable.

PMID- 11237697
TI  - Purification and characterization of human cell--cell adhesion molecule 1 (C
      CAM1) expressed in insect cells.
AB  - The cell--cell adhesion molecule 1 (C-CAM1) plays an important role as a tumor
      suppressor for prostate cancer. Decreased expression of C-CAM1 was detected in
      prostate, breast, and colon carcinoma. Reexpression of C-CAM1 in prostate and
      breast cancer cell lines was able to suppress tumorigenicity in vivo. These
      observations suggest that C-CAM1 may be used as a marker for cancer detection or
      diagnosis. To generate monoclonal antibodies specific to C-CAM1, we have
      overexpressed full-length human C-CAM1 in Sf9 cells using a baculovirus
      expression system. The protein was purified 104-fold using nickel affinity
      chromatography. About 0.4 mg purified C-CAM1 was obtained from 200 mg of infected
      cells. When the purified protein was digested with peptidyl-N-glycosidase, the
      apparent mobility of the protein on SDS--PAGE changed from 90 to 58 kDa, which is
      close to the molecular weight predicted from the cloned cDNA sequence. This
      observation suggests that C-CAM1 was glycosylated on asparagine residues when
      expressed in Sf9 cells. Western blotting and internal protein sequencing analysis
      confirmed that the purified protein is human C-CAM1. Biochemical and functional
      assays indicate that this protein expressed in Sf9 cells displays characteristics
      similar to those of native protein, including adhesion function and glycosylation
      modification. Using this protocol, sufficient quantity of this protein can be
      produced with purity suitable for monoclonal antibody generation and biochemical
      study.

PMID- 11237698
TI  - Copurification of the Lac repressor with polyhistidine-tagged proteins in
      immobilized metal affinity chromatography.
AB  - One of the commonly used resins for immobilized metal affinity purification of
      polyhistidine-tagged recombinant proteins is TALON resin, a cobalt (II)-
      carboxymethylaspartate-based matrix linked to Sepharose CL-6B. Here, we show that
      TALON resin efficiently purifies the native form of Lac repressor, which
      represents the major contaminant when (His)(6)-tagged proteins are isolated from
      Escherichia coli host cells carrying the lacI(q) gene. Inspection of the crystal
      structure of the repressor suggests that three His residues (residues 163, 173,
      and 202) in each subunit of the tetramer are optimally spaced on an exposed face
      of the protein to allow interaction with Co(II). In addition to establishing a
      more efficient procedure for purification of the Lac repressor, these studies
      indicate that non-lacI(q)-based expression systems yield significantly purer
      preparations of recombinant polyhistidine-tagged proteins.

PMID- 11237699
TI  - Purification of a fragment of MDM2 for production of polyclonal antisera.
AB  - A histidine-tagged, carboxy-terminal fragment of the murine double minute 2 gene
      product, p90(MDM2), was purified by Ni--NTA chromatography and preparative gel
      electrophoresis. The purified MDM2 fragment was used to generate polyclonal
      antisera that recognize multiple species of MDM2 proteins, including the
      inhibitor of p53, p90(MDM2), as well as the activator of p53, p76(MDM2). The
      antibodies are useful for Western analysis, immunoprecipitation, and
      immunofluorescence.

PMID- 11237700
TI  - The Family of Yellow-Related Drosophila melanogaster Proteins.

PMID- 11237701
TI  - Involvement of TGF-beta in inhibitory effects of negatively charged liposomes on
      nitric oxide production by macrophages stimulated with lps.
AB  - We examined the role of TGF-beta in the inhibitory effects of negatively charged
      liposomes composed of phosphatidylserine (PS-liposomes) on nitric oxide (NO)
      production by macrophages stimulated with LPS. The expression of TGF-beta mRNA
      increased when mouse peritoneal macrophages were treated with PS-liposomes. The
      inhibitory effect of PS-liposomes on NO production was restored by treatment with
      anti-TGF-beta antibody. Furthermore, NO production, iNOS mRNA expression, and
      iNOS protein induction by LPS were inhibited by treatment of macrophages with TGF
      beta as well as PS-liposomes. These results indicated that PS-liposomes down
      regulate NO production by macrophages through the induction of TGF-beta and
      suggested that TGF-beta may suppress NO production upstream of the transcription
      of iNOS mRNA.

PMID- 11237702
TI  - Unusual role of Tyr588 of neuronal nitric oxide synthase in controlling substrate
      specificity and electron transfer.
AB  - Nitric oxide (NO) is synthesized from l-Arg via N(G)-hydroxyl-l-Arg (NHA) in the
      heme active site of nitric oxide synthase (NOS). According to the crystal
      structure of other NOS isoforms, the carboxylate group of l-Arg hydrogen bonds to
      the hydroxyl group of the conserved Tyr588 residue in the heme distal site of
      neuronal NOS (nNOS). Indeed, the nNOS mutations Tyr588His, Tyr588Ser, and
      Tyr588Phe markedly increased the dissociation constants for l-Arg and NHA by 2.2
      8.2-fold and 1.5-3.9-fold, respectively. Similarly, Tyr588His and Tyr588Ser
      mutations markedly decreased the l-Arg-driven NO formation rates by 50 and 30%
      than that of the wild type, respectively. However, the catalytic activities of
      the same mutants using NHA were higher than that of the wild type by up to 136%.
      As a result, the turnover ratio of NHA to l-Arg was 4.12 for the Tyr588Ser
      mutant, compared with 1.07 for the wild-type enzyme. Intriguingly, heme reduction
      rates for the Tyr588 mutants were much lower than for wild type by two orders of
      magnitude.

PMID- 11237703
TI  - The seventh transmembrane domain of cc chemokine receptor 5 is critical for MIP
      1beta binding and receptor activation: role of MET 287.
AB  - CC chemokine receptor 5 (CCR5) is a high-affinity receptor for macrophage
      inflammatory protein (MIP)-1beta and functions as the major coreceptor for entry
      of macrophage-tropic (M-tropic) human immunodeficiency virus type 1 (HIV-1). To
      evaluate the role of transmembrane domains (TM) in the receptor function of CCR5,
      the seventh transmembrane domain (TM7) was examined in a series of chimeric
      receptor constructs including CCR5TM (CCR5 backbone/CCR5 TM7 replaced with CCR1
      TM7) and mutants of CCR5TM. The CCR5TM chimera exhibited a dramatic reduction in
      receptor activation, as well as little or no MIP-1beta binding. Further
      mutational analysis revealed that Met 287 in TM7 of CCR5 is a critical molecular
      determinant for both MIP-1beta binding and receptor activation. Interestingly,
      all of the chimeric/mutated receptors were biologically active in an HIV-1
      coreceptor fusion assay, demonstrating that chemokine binding is independent of
      HIV-1 coreceptor activity.

PMID- 11237704
TI  - Expression of NAD(+)-dependent isocitrate dehydrogenase in brown adipose tissue.
AB  - cDNA clones significantly expressed in brown adipose tissue (BAT) but not in
      white adipose tissue (WAT) of rats were isolated by use of a PCR-select cDNA
      subtraction kit. Of the isolated clones, structural features of two of them, 2-58
      and 2-67, were studied in detail. The results indicated that these clones were
      cDNAs encoding alpha- and beta-subunits of rat NAD(+)-dependent isocitrate
      dehydrogenase (NAD(+)-ICDH). Previous biochemical study suggested the importance
      of NAD(+)-ICDH in metabolism in BAT; however, transcript levels of individual
      subunits of this enzyme in BAT had never been analyzed. In the present study,
      using these newly isolated cDNAs, we clearly demonstrate that the expression of
      three subunits of NAD(+)-ICDH was the most remarkable in BAT among the various
      tissues analyzed.

PMID- 11237705
TI  - A Novel mRNA-cDNA interference phenomenon for silencing bcl-2 expression in human
      LNCaP cells.
AB  - The templates required for inducing posttranscriptional gene silencing (PTGS)
      effects have been investigated in human prostate cancer LNCaP cells. Transfection
      of a mRNA-cDNA hybrid construct was found to result in a relatively long-term
      interference of specific gene expression. Androgen-stimulated expression of bcl-2
      has been reported to increase the tumorigenic and metastatic potentials of human
      prostate cancer LNCaP cells, as well as their resistance to many apoptotic
      stimuli. The addition of bcl-2 antisense oligonucleotides, however, restored
      apoptosis. Our studies demonstrate gene silencing effects of the mRNA-cDNA
      transfection that is similar to those of PTGS/RNAi in this in vitro prostate
      cancer cell model. A potential RNA-directed RNA polymerase activity was also
      detected which is alpha-amanitin-sensitive. These findings indicate that a novel
      gene silencing system may exist in mammalian cells.

PMID- 11237706
TI  - Myxothiazol induces H(2)O(2) production from mitochondrial respiratory chain.
AB  - Interruption of electron flow at the quinone-reducing center (Q(i)) of complex
      III of the mitochondrial respiratory chain results in superoxide production.
      Unstable semiquinone bound in quinol-oxidizing center (Q(o)) of complex III is
      thought to be the sole source of electrons for oxygen reduction; however, the
      unambiguous evidence is lacking. We investigated the effects of complex III
      inhibitors antimycin, myxothiazol, and stigmatellin on generation of H(2)O(2) in
      rat heart and brain mitochondria. In the absence of antimycin A, myxothiazol
      stimulated H(2)O(2) production by mitochondria oxidizing malate, succinate, or
      alpha-glycerophosphate. Stigmatellin inhibited H(2)O(2) production induced by
      myxothiazol. Myxothiazol-induced H(2)O(2) production was dependent on the
      succinate/fumarate ratio but in a manner different from H(2)O(2) generation
      induced by antimycin A. We conclude that myxothiazol-induced H(2)O(2) originates
      from a site located in the complex III Q(o) center but different from the site of
      H(2)O(2) production inducible by antimycin A.

PMID- 11237707
TI  - TNFalpha elicits association of PI 3-kinase with the p60TNFR and activation of PI
      3-kinase in adherent neutrophils.
AB  - Tumor necrosis factor (TNFalpha) is an incomplete secretagogue in neutrophils and
      requires the engagement of beta integrins to trigger secretion of superoxide
      anion (O(-)(2)). The p60 TNF receptor (p60TNFR) is responsible for signal
      transduction for activation of O(-)(2) generation. Activation of TNFalpha
      triggered O(-)(2) generation in neutrophils adherent to fibrinogen-coated
      surfaces involves the beta2 integrin receptor CD11b/CD18. Phosphoinositide 3
      kinase (PI 3-kinase) is essential for activation of O(-)(2) generation;
      wortmannin, an inhibitor of PI 3-kinase, inhibited TNFalpha-elicited O(-)(2)
      generation. p60TNFR immunoprecipitated from neutrophils was associated with
      immunoreactivity to PI 3-kinase in adherent neutrophils exposed to TNFalpha, but
      not in TNFalpha-treated neutrophils in suspension. In addition, PI 3-kinase
      immunoprecipitated from TNFalpha-activated neutrophils showed enhanced activity
      in adherent but not in nonadherent neutrophils. These findings suggest that
      synergism between CD11b/CD18 and p60TNFR in the presence of TNFalpha is required
      to elicit assembly of a signaling complex involving association of p60TNFR with
      PI 3-kinase, activation of PI 3-kinase, and generation of O(-)(2).

PMID- 11237708
TI  - Nondestructive quantification of neutral lipids by thin-layer chromatography and
      laser-fluorescent scanning: suitable methods for "lipidome" analysis.
AB  - A simple method for separation and quantification of neutral lipids was developed
      using thin-layer chromatography (TLC) and high-performance fluorescent scanning.
      Neutral lipid classes were separated using the double-developing TLC method and
      detected by rhodamine 6G and a laser-excited fluorescent scanner. The amount of
      lipids applied correlated with scanned intensity volume in a dose-dependent
      manner. The mass of each neutral lipid band was determined by comparing band
      intensities of unknown samples to dilution curves of authentic standards. After
      scanning the dye-sprayed TLC, acyl chain species of triglyceride (TG) extracted
      from TLC could be determined by gas chromatography. Using this method, we
      quantified the amounts of TG in mouse liver and found that the measured total
      mass of TG correlated with that obtained by enzymatic methods. Our method should
      provide the basic technique for "lipidome" analysis, designed to determine and
      compare total lipid classes and mass present in biological samples.

PMID- 11237709
TI  - Regulation of Pim-1 by Hsp90.
AB  - The protooncogene Pim-1 encodes serine/threonine protein kinases that are
      involved in cytokine-mediated cell proliferation and in lymphoma- and
      leukemogenesis. It is largely unknown how Pim-1 executes its biological effects.
      Here we show that Pim-1 physically interacts with heat shock protein 90 alpha and
      beta (Hsp90alpha and beta). The Hsp90-specific inhibitor geldanamycin (GA)
      induced a rapid degradation of Pim-1 and reduced its kinase activity. The
      expression of Hsp90alpha was regulated by a signal from the cytokine receptor
      gp130, as is Pim-1's expression. These results indicate that Hsp90 is
      coordinately regulated with Pim-1 and is involved in the stabilization and
      function of Pim-1.

PMID- 11237710
TI  - Radioligand binding properties of VV-hemorphin 7, an atypical opioid peptide.
AB  - Receptor binding properties of the hemoglobin-derived nonapeptide VV-hemorphin 7
      (Val-Val-Tyr-Pro-Trp-Thr-Gln-Arg-Phe-OH) were studied using both the unlabelled
      form and tritium-labelled derivative of the peptide. In binding studies using
      selective opioid radioligands, VV-hemorphin 7 exhibited a rank order of potency
      of mu > kappa >> delta. VV-hemorphin 7 was tritiated resulting in a compound with
      1.03 TBq/mmol (27.8 Ci/mmol) specific radioactivity. The maximal number of
      binding sites was found to be 66.5 pmol/mg protein with an affinity of 82.1 nM in
      rat brain membranes. In competition studies, marked similarity was observed to
      the binding profile of the naturally occurring opioid heptapeptide Met-enkephalin
      Arg-Phe (MERF) and its analogues to their naloxone-insensitive binding site. The
      common -Arg-Phe sequence at the carboxyl terminal end, which is similar to those
      of other endogenous peptides (-Arg-Phe-NH(2) in neuropeptide FF and FMRF-NH(2))
      brings attention to the C-terminal end of the molecule and points to the possible
      existence of a common nonopioid binding site in mammals.

PMID- 11237711
TI  - Overexpression of connective tissue growth factor/hypertrophic chondrocyte
      specific gene product 24 decreases bone density in adult mice and induces
      dwarfism.
AB  - Connective tissue growth factor/hypertrophic chondrocyte-specific gene product 24
      (CTGF/Hcs24) is a multifunctional growth factor for fibroblasts, chondrocytes,
      and vascular endothelial cells. In the present study, we established transgenic
      (Tg) mice that overproduce CTGF/Hcs24 under the control of mouse type XI collagen
      promoter. Tg mice could develop and their embryonic and neonatal growth occurred
      normally. But they showed dwarfism within a few months of birth. X-ray analysis
      revealed that their bone density was decreased compared with normal mice. The
      femurs in the hindlimbs in particular showed an apparent low density. These
      results indicated that overexpression of CTGF/Hcs24 affects certain steps of
      endochondral ossification. In addition, the testes were much smaller than normal
      and fertility was affected in Tg mice, indicating that CTGF/Hcs24 may also
      regulate the embryonic development of the testis.

PMID- 11237712
TI  - Activation of BMK1 via tyrosine 1062 in RET by GDNF and MEN2A mutation.
AB  - Big mitogen-activated protein kinase 1 (BMK1) is a new member of mitogen
      activated protein kinase (MAPK) family. In the present study, we investigated
      whether glial cell line-derived neurotrophic factor (GDNF) can induce activation
      of BMK1 through RET tyrosine kinase. Its activation reached a maximal level at 30
      min and continued at least for 120 min after GDNF stimulation. In addition, we
      detected BMK1 activation in NIH3T3 cells expressing RET with a multiple endocrine
      neoplasia (MEN) 2A mutation. The level of BMK1 activation markedly decreased by
      replacement of tyrosine 1062 with phenylalanine (designated Y1062F) in RET,
      indicating the importance of downstream signaling via tyrosine 1062. However,
      although both RAS/MAPK and phosphatidylinositol 3-kinase (PI3-K)/AKT signaling
      pathways are activated via tyrosine 1062, BMK1 activation by GDNF was not
      significantly impaired by treatment with an MEK1 inhibitor, PD98059, or two
      distinct PI3-K inhibitors, LY294002 and wortmannin, suggesting that the RAS and
      PI3-K signaling pathways are not crucial for BMK1 activation by GDNF. Moreover,
      luciferase reporter assays revealed that RET-MEN2A mutant proteins can activate
      the MEF2C transcription factor that is known to be a cellular target for BMK1,
      and that its activation is impaired by the Y1062F mutation or by expression of a
      dominant negative form of MEK5.

PMID- 11237713
TI  - Extension of juxtamembrane domain of diphtheria toxin receptor arrests
      translocation of diphtheria toxin fragment A into cytosol.
AB  - Diphtheria toxin (DT) binds to the EGF-like domain of the DT receptor (DTR),
      followed by internalization and translocation of the enzymatically active
      fragment A into the cytosol. The juxtamembrane domain (JM) of the DTR is the
      linker domain connecting the transmembrane and EGF-like domains. We constructed
      mutants of DTRs with altered JMs and studied their abilities for DT intoxication.
      Although DTR mutants with extended JMs showed normal DT binding activity, the
      cells expressing the mutants showed both reduced translocation of DT fragment A
      into the cytosol and reduced sensitivity to DT, when compared with cells
      expressing wild-type DTR. These results indicate that the JM contributes to DT
      intoxication by providing a space appropriate for the interaction of DT with the
      cell membrane. The present study also indicates that consideration of epitopes of
      an immunotoxins would be an important factor in the design of potent
      immunotoxins.

PMID- 11237715
TI  - A novel centrosomal ring-finger protein, dorfin, mediates ubiquitin ligase
      activity.
AB  - We cloned a novel gene, Dorfin (double ring-finger protein), from human spinal
      cord. The Dorfin mRNA transcript was 4.4 kb and expressed ubiquitously in many
      organs as well as in the central nervous system, including the spinal cord.
      Dorfin encoded 838 amino acid protein Dorfin, which contains two RING-finger
      motifs and an IBR (in between RING-fingers) motif at its N-terminus. Dorfin is a
      short-lived protein. Treatment with MG132, a potent proteasome inhibitor,
      resulted in the accumulation of ubiquitinated Dorfin and Dorfin-associated
      cellular proteins in cultured cells. Dorfin bound specifically with human
      ubiquitin-conjugating enzymes UbcH7 and UbcH8 through the RING-finger/IBR domain.
      Partial deletion of the RING-finger/IBR domain eliminated these interaction and
      ubiquitination activities. These results strongly suggest that Dorfin is a new
      member of RING-finger type ubiquitin ligase. Dorfin is localized in the
      centrosome and probably functions in the microtubule organizing centers.

PMID- 11237714
TI  - DSCAM, a highly conserved gene in mammals, expressed in differentiating mouse
      brain.
AB  - Down Syndrome Cell Adhesion molecule (DSCAM) is a member of the immunoglobulin
      superfamily, and represents a novel class of neuronal cell adhesion molecules. In
      order to understand the cellular functions of DSCAM, we isolated full-length
      mouse and human cDNA clones, and analysed its expression during mouse development
      and differentiation. Sequence analysis of the human DSCAM cDNA predicted at least
      33 exons that are distributed over 840 kb. When compared to human DSCAM, the
      mouse homologue showed 90 and 98% identity at the nucleotide and amino acid
      levels, respectively. In mouse, DSCAM is located on 16C, the syntenic region for
      human chromosome band 21q22 and also the region duplicated in mouse DS models.
      DSCAM gene is predicted to encode an approximately 220-kDa protein, and its
      expression shows dynamic changes that correlate with neuronal differentiation
      during mouse development. Our results suggest that DSCAM may play critical roles
      in the formation and maintenance of specific neuronal networks in brain.

PMID- 11237716
TI  - In synergy with noggin and follistatin, Xenopus nodal-related gene induces sonic
      hedgehog on notochord and floor plate.
AB  - In early development of vertebrates, sonic hedgehog functions in dorsal-ventral
      patterning of dorsal tissue (nervous system and somites). In Xenopus, sonic
      hedgehog (Xshh) is first expressed in the Spemann organizer/notochord and floor
      plate. We report here the mechanism governing Xshh mRNA induction in these
      regions. In animal cap assays, the antagonizing BMPs signal was not sufficient to
      induce Xshh mRNA expression; however, it could induce Xshh mRNA expression in the
      presence of Xnr-1. In whole embryos, when secondary axes were induced by
      coexpressing noggin and Xnr-1 or follistatin and Xnr-1, Xshh mRNA expression was
      observed in the notochord and floor plate within the induced axes. It seems
      apparent that spatially restricted Xshh mRNA expression is determined as
      intersection of the two signals.

PMID- 11237718
TI  - Homocysteine inhibits angiogenesis in vitro and in vivo.
AB  - Homocysteine has been reported to inhibit endothelial cell proliferation, which
      is closely related to angiogenesis. However, the relationship between
      homocysteine and angiogenesis is unknown. To clarify whether homocysteine would
      inhibit angiogenesis in vitro and in vivo, we examined the effect of homocysteine
      on tube formation by bovine aortic endothelial cells (BAECs) and by human
      microvessel endothelial cell-1 (HMEC-1) in vitro, and on angiogenesis in vivo
      using the chorioallantoic membrane (CAM) assay, as well as on BAEC proliferation
      and migration. Homocysteine, but not cysteine, inhibited BAEC proliferation,
      migration, and tube formation in a dose-dependent manner at concentrations from 0
      to 10 mM. Homocysteine also inhibited tube formation by HMEC-1s. In these assay,
      50% inhibition was induced by about 1 mM homocysteine. In the in vivo CAM assay,
      0, 10, 100, 500, and 1000 microgram homocysteine induced an avascular zone by 0,
      0, 16.7, 53.3 and 76.5%, respectively, also showing a dose-dependent effect. It
      was suggested that homocysteine inhibited angiogenesis by preventing
      proliferation and migration of endothelial cells.

PMID- 11237717
TI  - Redox-sensitive regulation of lox-1 gene expression in vascular endothelium.
AB  - Oxidative stress has been implicated in atherosclerosis and its underlying
      conditions. LOX-1 is a novel endothelial receptor for oxidized low-density
      lipoprotein which might mediate endothelial dysfunction and subsequent
      atherogenesis. In the present study, we examined LOX-1 gene regulation by
      oxidative stress. First, superoxide anions generated by hypoxanthine and xanthine
      oxidase as well as hydrogen peroxide increased LOX-1 mRNA expression in cultured
      aortic endothelial cells. Homocysteine, an atherogenic substance believed to
      exert its effects through oxidative stress, enhanced endothelial LOX-1 gene
      expression, which was suppressed by N-acetylcysteine. Second, rats receiving
      angiotensin II for 10 days manifested hypertension and LOX-1 upregulation in
      aortic endothelium via AT1 receptor. Tempo, a superoxide dismutase mimetic,
      alleviated LOX-1 augmentation induced by angiotensin II. These results indicated
      redox-sensitive upregulation of LOX-1 mRNA in both in vitro and in vivo systems,
      suggesting its potential role in atherosclerosis.

PMID- 11237720
TI  - A putative prokaryote voltage-gated Ca(2+) channel with only one 6TM motif per
      subunit.
AB  - Until now, voltage-gated Ca(2+) channel proteins have been found only in
      eukaryotes. Here we report that a gene recently discovered in the eubacterium
      Bacillus halodurans codes for a protein closely related to eukaryotic Ca(2+)
      channels, but that has only one 6-transmembrane-segement (6TM) motif, instead of
      four, in its pore-forming subunit. This is supported by the comparison of
      consensus sequences, which, along with the patterns of residue conservation,
      indicates a similar structure in the membrane to voltage-gated K(+) channels.
      From this we hypothesize that Ca(2+) channels originally evolved in bacteria, and
      that the specific eubacteria protein highlighted here is an ideal candidate for
      structure determination efforts.

PMID- 11237719
TI  - A human hepatoma cell line expressing hepatitis c virus nonstructural proteins
      tightly regulated by tetracycline.
AB  - Nonstructural (NS) proteins of hepatitis C virus (HCV) play major roles in viral
      replication and the pathogenesis of liver diseases. Current studies on antiviral
      strategies targeting these proteins have been hampered by the lack of efficient
      cell culture systems. Combining tetracycline-regulated gene expressing system and
      enhanced green fluorescent protein (EGFP), we generated a human hepatoma cell
      line inducibly expressing the HCV NS proteins. This cell line exhibited high
      induction of a full NS transcript ( approximately 7 kb). In the absence of
      tetracycline, NS proteins 3, 4A, and 5A of mature sizes were detected by
      immunoblot analysis and the induction of NS proteins 3 to 5B are confirmed by
      immunofluorescent staining. Using DNA microarray analysis, we characterized the
      changes in mRNA expression profile of 6416 genes and identified several genes,
      whose mRNAs are specifically upregulated by the induction of NS proteins. This
      cell line provides a unique in vitro hepatoma cell system for the investigation
      of structural and functional properties of HCV NS proteins.

PMID- 11237721
TI  - Expression of l-3-phosphoserine phosphatase is regulated by reconstituted
      basement membrane.
AB  - Reconstituted basement membrane (Matrigel) promotes differentiation of
      endometrial adenocarcinoma cells in vitro. However, little is known about the
      molecular basis of these in vitro differentiation processes. Using differential
      display RT-PCR to search for potential molecular markers we screened for genes
      which respond to contact to basement membrane by alteration of expression levels.
      Here we report that the cDNA MT32 represents an mRNA with a time dependent
      biphasic response pattern to contact to basement membrane. Characterizing MT32
      revealed that the sequence of MT32 is identical to l-3-phosphoserine phosphatase.
      PCR analysis of l-3-phosphoserine phosphatase expression surprisingly revealed at
      least three variants of this enzyme. In summary, and in view of the literature, l
      3-phosphoserine phosphatase and potential variants or family members represent
      molecular markers to study regulation of gene expression by components of the
      extracellular matrix. In conclusion, l-3-phosphoserine phosphatase(s) may be
      important in endometrial carcinogenesis since this enzyme synthesizes important
      metabolic intermediates which serve both as building blocks for peptide synthesis
      and for signal transducing molecules.

PMID- 11237723
TI  - Identification of active regions for neurite outgrowth activity of neurocrescin.
AB  - We previously identified and cloned a neurite outgrowth promoting protein,
      Neurocrescin (NC), from the extract of the chick denervated leg muscles. In this
      study, we explored the active region of NC for neurite outgrowth. Using the
      deletion mutants of NC, we tested their neurite outgrowth activity in the
      cultured telencephalic neurons of E5 chick embryos. We found three regions which
      independently had significant neurite outgrowth activity comparable with that of
      the extract of the chick denervated leg muscles. These regions were not
      homologous to any well-known active sites such as the laminin active region,
      IKVAV. In parallel, searching the endogenous deletion mutants of NC in the rat
      brain, we cloned a mutant in which the region including the larger part of one of
      the three active regions was deleted. The neurite outgrowth activity of the
      mutant was significantly lower than that of normal NC. These results suggest the
      physiological significance of these active regions.

PMID- 11237722
TI  - Etherphospholipid biosynthesis and dihydroxyactetone-phosphate acyltransferase:
      resolution of the genomic organization of the human gnpat gene and its use in the
      identification of novel mutations.
AB  - Etherphospholipids are characterised by the occurrence of an alkyl- or alkenyl
      group at the sn-1 position of the glycerol backbone. Peroxisomes play an
      essential role in the formation of etherphospholipids since the first two enzymes
      of the biosynthetic pathway are strictly peroxisomal. The function of
      plasmalogens is still an enigma but the recent identification of patients
      suffering from an isolated defect in either dihydroxyacetone phosphate
      acyltransferase (GNPAT) or alkyldihydroxyacetone phosphate synthase provides
      conclusive evidence that plasmalogens play an essential role for human survival
      and functioning. In this paper we report the complete genomic organisation of the
      GNPAT gene coding for the peroxisomal dihydroxyacetone phosphate acyltransferase.
      The gene is located on chromosome 1q42.12-43. It spans approximately 28 kb and
      consists of 16 exons and 15 introns. This information was used to analyse the
      GNPAT gene in 12 patients with GNPAT deficiency. All patients analysed were found
      to have mutations in their GNPAT gene. Of the 9 different mutations found, 2 were
      missense mutations, 2 small deletions, 1 insertion and 3 mutations were within
      splice donor/acceptor-sites. Another mutation created an alternative splice donor
      site causing the partial deletion of an exon. The data obtained provide
      conclusive evidence for the major role of GNPAT in etherphospholipid
      biosynthesis.

PMID- 11237724
TI  - Nitric oxide prevents gamma-radiation-induced cell cycle arrest by impairing p53
      function in MCF-7 cells.
AB  - We previously reported that nitric oxide (NO) released from S-nitrosoglutathione
      induces conformational change of the p53 tumor-suppressor protein that impairs
      its DNA-binding activity in vitro. We now demonstrate that MCF-7 cells
      preincubated in the presence of 0.5-1 mM S-nitrosoglutathione for 4 h before
      gamma-irradiation failed to arrest in the G1 phase of the cell cycle, whereas
      those gamma-irradiated without S-nitrosoglutathione exhibited a normal cell cycle
      arrest. The S-nitrosoglutathione-treated cells did not express the p53 target
      gene p21(waf-1) after gamma-irradiation, although p21(waf-1) was strongly
      expressed in cells irradiated in the absence of S-nitrosoglutathione. These
      results strongly suggest that NO impairs the function of p53 possibly via
      conformational change and/or amino acid modifications. On the other hand, cells
      incubated for 16 h in the presence of 1 mM S-nitrosoglutathione underwent
      apoptosis with accumulation of the pro-apoptotic protein Bax. This Bax
      accumulation, however, was shown to occur via a p53-independent pathway.

PMID- 11237725
TI  - Uncoupling protein 3 and peroxisome proliferator-activated receptor gamma2
      contribute to obesity and diabetes in palauans.
AB  - We examined the genetic contribution of single nucleotide polymorphisms (SNPs) of
      the energy metabolism-related genes, including beta 3 adrenergic receptor
      (beta3AR), apolipoprotein E (apo-E), promoter of uncoupling protein 3 (UCP3-p),
      peroxisome proliferator-activated receptor gamma 2 (PPARgamma2) and leptin
      receptor (LEPR) to metabolic disorders, in 118 inhabitants of Palau. The data
      were statistically analyzed and ethnically compared to correlate SNPs and their
      metabolic parameters. UCP3-p (P < 0.01) and PPARgamma2 (p = 0.05) correlated with
      plasma HbA1c, and UCP3-p correlated with fasting blood glucose (P < 0.01) in
      males, but not in females. UCP3-p correlated with body fat (%) (P < 0.01) in
      females, but not in males. Plasma leptin levels and apo-E were correlated in both
      groups. The frequency of SNPs for PPARgamma2, LEPR, and UCP3-p are significantly
      different between Palauans and Caucasians.

PMID- 11237726
TI  - Identification of a potent and nonpeptidyl ccr3 antagonist.
AB  - CCR3 is expressed in a variety of leukocyte subsets, especially eosinophils, and
      may be involved in allergic disorders such as atopic asthma. To clarify the
      pathophysiological roles of CCR3 in allergic disorders, we developed a
      nonpeptidyl CCR3 antagonist. This antagonist, which is referred to as "Compound
      X," that inhibited the binding of [(125)I]Eotaxin to CHO cells transfected with
      human CCR3 with an IC(50) value of 2.3 nM. In human eosinophils, Compound X also
      inhibited Eotaxin-induced increases in intracellular Ca(2+) concentrations and
      chemotaxis. Thus, Compound X appears to be a highly potent CCR3 antagonist. These
      findings suggest that Compound X may be a useful tool for elucidating the
      pathophysiological roles of CCR3 in a variety of allergic disorders.

PMID- 11237727
TI  - Investigation of subunit function in ADP-glucose pyrophosphorylase.
AB  - ADP-glucose pyrophosphorylase (AGPase), a key regulatory enzyme in higher plant
      starch biosynthesis, is composed of a pair of large and small subunits
      (alpha(2)beta(2)). Current evidence suggests that the large subunit has primarily
      a regulatory function, while the small subunit has both regulatory and catalytic
      roles. To define the structure-function relationship of the large subunit (LS),
      the LS of potato AGPase was subjected to chemical mutagenesis and coexpressed
      with the wild-type (WT) small subunit (SS) cDNA in an AGPase defective
      Escherichia coli strain. An LS mutant (M143) was isolated, which accumulated very
      low levels of glycogen compared to the WT recombinant AGPase, but maintained
      normal catalytic activity when assayed under saturating conditions. Sequence
      analysis revealed that M143 has a single amino acid change, V463I, which lies
      adjacent to the C-terminus. This single mutation had no effect on the Km for ATP
      and Mg(2+), which were similar to the WT enzyme. The K(m) for glucose 1-P,
      however, was sixfold higher than the WT enzyme. These results suggest that the LS
      plays a role in binding glucose 1-P through its interaction with the SS.

PMID- 11237728
TI  - The cytochrome c domain of dimeric cytochrome cd(1) of Paracoccus pantotrophus
      can be produced at high levels as a monomeric holoprotein using an improved c
      type cytochrome expression system in Escherichia coli.
AB  - Cytochrome cd(1) nitrite reductase from Paracoccus pantotrophus is a dimer;
      within each monomer there is a largely alpha-helical domain that contains the c
      type cytochrome centre. The structure of this domain changes significantly upon
      reduction of the heme iron, for which the ligands change from His17/His69 to
      Met106/His69. Overproduction, using an improved Escherichia coli expression
      system, of this c-type cytochrome domain as an independent monomer is reported
      here. The properties of the independent domain are compared with those when it is
      part of dimeric holo or semi-apo cytochrome cd(1).

PMID- 11237729
TI  - C7, a novel nucleolar protein, is the mouse homologue of the Drosophila late puff
      product L82 and an isoform of human OXR1.
AB  - The C7 gene was identified in a project aimed to characterize differential gene
      expression upon attachment of cells to extracellular matrix proteins in vitro. C7
      is the homologue of Drosophila L82, a late puff gene (Stowers et al. (1999) Dev.
      Biol. 213, 116-130) and human OXR1, a gene, which protects cells against
      oxidation (Volkert et al. (2000) Proc. Natl. Acad. Sci. USA 97, 14530-14535). All
      are transcribed into multiple splice forms with a common 3' domain. Additional
      members of this novel gene family are found in a number of eukaryotic species. In
      the mouse, the C7 gene is highly and broadly expressed during development in at
      least 4 splice forms, 3 of which were sequenced. In the adult, the C7 gene is
      most highly expressed in brain and testis. Antibodies to recombinant C7 protein
      localized to nucleoli in a variety of cell types, suggesting that C7 may be
      involved in the formation or function of this important organelle.

PMID- 11237730
TI  - Expression study of genes involved in iron metabolism in human tissues.
AB  - Iron is required in all organisms for crucial functions, as a number of proteins
      need iron for activity. Mutations of the genes encoding proteins involved in iron
      uptake, transport, and utilization result in various human disorders or animal
      models with very different clinical presentations and organ involvement. However,
      little is known concerning the expression of iron metabolism genes in various
      human tissues and their eventual concerted regulation. We therefore examined the
      expression levels of various genes involved in iron uptake, reduction, and
      storage, in Fe-S protein biogenesis, in mitochondrial electron transport chain,
      plus the two SOD genes, in human adult tissues by Northern blot analysis. We
      observed that most of these genes were ubiquitously expressed, but that their
      transcript showed strongly different levels in the various tissues investigated
      denoting different mechanisms for iron utilization in various organs. However,
      surprisingly, no correlation could be made between expression pattern of these
      genes and the clinical presentation resulting in their mutations.

PMID- 11237731
TI  - A novel single nucleotide polymorphism altering stability and activity of CYP2a6.
AB  - CYP2A6 is known as a major cytochrome P450 (CYP) responsible for the oxidation of
      nicotine and coumarin in humans. In this study, we explored genetic
      polymorphisms, which reduce CYP2A6 activity in Japanese. Two novel mutations in
      exon 9 of the CYP2A6 gene were found. A single nucleotide polymorphism of T1412C
      and G1454T resulted in Ile471Thr and Arg485Leu substitution, respectively. The
      frequency of the former variant allele was considerably high (15.7%), while the
      latter variant appeared to be a rare polymorphism. Heterologous expression of
      CYP2A6 using a cDNA possessing C instead of T-base at codon 471 in Escherichia
      coli caused remarkable reduction of the stability of holoenzyme at 37 degrees C.
      Furthermore, this variant enzyme almost lacked nicotine C-oxidase activity,
      although coumarin 7-hydroxylase activity was still observed. These data suggest
      that individuals homozygous for the T1412C variant allele or heterozygous for
      this and a defect allele such as the CYP2A6*4 may be poor metabolizer of
      nicotine, but not coumarin.

PMID- 11237732
TI  - Molecular cloning and characterization of FRAT2, encoding a positive regulator of
      the WNT signaling pathway.
AB  - FRAT1 positively regulates the WNT signaling pathway by stabilizing beta-catenin
      through the association with glycogen synthase kinase-3beta. Here, we have cloned
      FRAT2 cDNAs, spanning the complete coding sequence, from a human fetal lung cDNA
      library. FRAT2 encoded 233 amino-acid protein, which showed 77.3% total amino
      acid identity with FRAT1. FRAT2 and FRAT1 were more homologous in the acidic
      domain (96% identity), the proline-rich domain (92% identity), and the GSK-3beta
      binding domain (100% identity). The FRAT2 gene was mapped to human chromosome
      10q24.1. The FRAT2 mRNA of 2.4-kb in size was relatively highly expressed in
      MKN45 (gastric cancer), HeLa S3 (cervical cancer), and K-562 (chronic myelogenous
      leukemia). Xenopus axis duplication assay revealed that the wild-type FRAT2 mRNA,
      but not the mutant FRAT2 mRNA lacking the acidic domain and the proline-rich
      domain, has the capacity to induce the secondary axis. These results indicate
      that FRAT2, just like FRAT1, functions as a positive regulator of the WNT
      signaling pathway. Thus, up-regulation of FRAT2 in human cancer might be
      implicated in carcinogenesis through activation of the WNT signaling pathway.

PMID- 11237733
TI  - Polyphosphate:AMP phosphotransferase and polyphosphate:ADP phosphotransferase
      activities of Pseudomonas aeruginosa.
AB  - In Pseudomonas aeruginosa PAO1, we have found massive polyphosphate:AMP
      phosphotransferase activity and polyphosphate:ADP phosphotransferase activity
      known as the reverse catalytic activity of polyphosphate kinase which
      participates in polyphosphate synthesis in the bacterium. Biochemical analysis
      using the partially purified polyphosphate:ADP phosphotransferase has revealed
      that it is independent of polyphosphate kinase and can function as polyphosphate
      dependent nucleoside diphosphate kinase which most prefers GDP to the other three
      nucleoside diphosphates as a phospho-acceptor. It has been also demonstrated that
      polyphosphate:AMP phosphotransferase activity marked in the bacterium mainly
      originates from the combined action of the polyphosphate:ADP phosphotransferase
      described above and adenylate kinase. Both of the polyphosphate-utilizing
      activities require short polyP as a phospho-donor whose chain length is <75.

PMID- 11237734
TI  - Isolation of endothelial cells from brain, lung, and kidney: expression of the
      multidrug resistance P-glycoprotein isoforms.
AB  - Endothelial cells (EC) were isolated from brain, lung, and renal cortex using
      magnetic microbeads cross-linked to an antibody directed against the platelet
      endothelial cell adhesion molecule-1 (PECAM-1). Levels of endothelial nitric
      oxide synthase (eNOS) and PECAM-1 were measured by Western blots and both were
      enriched in the positively selected EC fractions. The multidrug resistance P
      glycoprotein (P-gp) was strongly enriched (59-fold) in the EC fraction from brain
      and was absent in the negative fraction, in which the glial fibrillary acidic
      protein (GFAP), an astrocyte marker, was present. Lower P-gp levels were detected
      in EC from renal cortex and lung. Reverse transcription-polymerase chain reaction
      analysis showed that the mdr1a gene was preferentially expressed in EC fraction
      from the brain. The mdr1b gene was found in EC from renal cortex whereas both
      mdr1 genes were detected in EC from lung. Our results indicate that EC can be
      isolated using microbeads and that the isoform of P-gp found in brain is mostly
      mdr1a, associated with EC.

PMID- 11237735
TI  - A mammalian radial spokehead-like gene, RSHL1, at the myotonic dystrophy-1 locus.
AB  - Ciliary function is essential for normal cellular activity in all species from
      simple protozoa upwards. In humans, ciliary dysmotility or complete immobility
      have been identified in autosomal recessive multisystemic diseases characterized
      by recurrent respiratory tract infections and male subfertility due to impaired
      sperm mobility. Linkage to human chromosome 19q13.3 has been published for some
      families but no candidate genes have been identified. We report the first
      identification of a mammalian homolog of a radial spokehead-like protein, with
      high homology to proteins of sea urchins and the protozoan Chlamydomonas
      reinhardtii, at the myotonic dystrophy-1 locus (chromosome19q13.3). In the lower
      organisms, these proteins are important in normal ciliary or flagellar action,
      including that of sea urchin spermatozoa. Expression of the mammalian homolog was
      detected in the adult testis. We suggest that this gene, which we have called
      Radial Spokehead-Like 1 (RSHL1), is a candidate gene for familial primary ciliary
      dyskinesia.

PMID- 11237736
TI  - T cell activation signals upregulate CBP-dependent transcriptional activity.
AB  - The transcriptional coactivator CREB-binding protein (CBP) is known to play an
      important role in coupling signal transduction pathways to changes in gene
      expression. In many cases, this is achieved by the stimulus-specific recruitment
      of CBP to promoter-bound transcription factors. However, a number of recent
      studies have suggested that signal transduction pathways can also directly
      influence CBP-mediated transcriptional activity. Here we show that in Jurkat
      cells the activity of the CBP C-terminal transactivation domain is strongly
      upregulated in response to either T cell receptor stimulation or the combination
      of ionomycin and phorbol ester. We further show that maximal stimulation of CBP
      mediated transcription requires the synergistic activation of both the
      calcineurin and Ras-MAPK signaling pathways. These results indicate that CBP can
      function as a T cell activation-inducible transcriptional coactivator and is
      therefore likely to play an important role in T cell activation-induced gene
      expression.

PMID- 11237737
TI  - Cysteine residues are involved in structure and function of melanocortin 1
      receptor: Substitution of a cysteine residue in transmembrane segment two
      converts an agonist to antagonist.
AB  - Reduction of disulfide bonds in human melanocortin 1 receptor (hMC1R) with
      increasing concentrations of DTT (dithiothreitol) resulted in a decrease in the
      binding of [125I]-ACTH (adrenocorticotropic hormone, L-isomer) in an uniphasic
      manner and a decrease in [125I]-NDP-MSH ([Nle(4),D-Phe(7)]-alpha-melanocyte
      stimulating hormone; D-isomer) binding in a biphasic manner. Pretreatment of
      hMC1R with 10 mM DTT resulted in a 36-fold loss of affinity for alpha-MSH (L
      isomer) without affecting the affinity of NDP-MSH (D-isomer). To characterize the
      role of individual cysteine residues, we employed site-directed mutagenesis to
      substitute cysteine by glycine at all fourteen positions in hMC1R and analysed
      wild-type and mutant receptors for ligand binding and cAMP signalling. Single
      point mutation of four cysteine residues in extracellular loops to glycine (C35G,
      C267G, C273G, and C275G) resulted in a complete loss of binding for [125I]-NDP
      MSH. Moreover, mutants with normal ligand binding, at positions C191G
      (transmembrane segment 5), C215G (third intracellular loop), and C315G (C
      terminal loop) failed to generate cAMP signal in response to both agonists alpha
      MSH and NDP-MSH. Mutant at position C78G (with wild-type binding to alpha-MSH as
      well as NDP-MSH) generated a cAMP signal in response to alpha-MSH (identical to
      wild-type hMC1R) but interestingly could not be stimulated by NDP-MSH. Moreover,
      this single amino acid substitution converted NDP-MSH from being an agonist to
      antagonist at the C78G mutant receptor. These findings demonstrate that (i) alpha
      MSH and ACTH (L-isomers) are different from D-isomer NDP-MSH in their sensitivity
      to DTT for receptor binding, (ii) cysteine residues in N-terminus and
      extracellular loop three make disulfide bridges and are needed for structural
      integrity of hMC1R, (iii) cysteine residues in transmembrane segments and
      intracellular loops are required for receptor-G-protein coupling, (iv) C78 in
      transmembrane segment two is required for generating a functional response by D
      isomer agonist (NDP-MSH) but not by L-isomer agonist (alpha-MSH), and (v) wild
      type receptor agonist NDP-MSH is an antagonist at the mutant C78G receptor.

PMID- 11237738
TI  - Anthranilate synthase without an LLES motif from a hyperthermophilic archaeon is
      inhibited by tryptophan.
AB  - Tk-trpE and Tk-trpG, the genes that encode the two subunits of anthranilate
      synthase from the hyperthermophilic archaeon Thermococcus kodakaraensis KOD1,
      have been expressed independently in Escherichia coli. The anthranilate synthase
      complex (Tk-AS complex) was obtained by heat-treatment of the mixture of cell
      free extracts containing each recombinant protein, Tk-TrpE (alpha subunit) and Tk
      TrpG (beta subunit), at 85 degrees C for 10 min. Further purification of Tk-AS
      complex was carried out by anion-exchange chromatography followed by gel
      filtration. Molecular mass estimations from gel-filtration chromatography
      indicated that Tk-AS complex was a heterodimer (alphabeta). The complex displayed
      both ammonia- and glutamine-dependent anthranilate synthase activities, and could
      not utilize asparagine as an ammonia donor. The optimal pH was pH 10.0 and the
      optimal temperature was 85 degrees C in both cases. Mg2+ was necessary for the
      anthranilate synthase activity. At 75 degrees C, the K(m) values of chorismate
      for ammonia- and glutamine-dependent activities were 13.8 and 3.4 microM,
      respectively. The K(m) value of Mg2+ was 20.5 microM. The K(m) values of
      glutamine and NH4Cl were 88 microM and 5.6 mM, respectively. Although Tk-TrpE
      displayed 47.6% similarity with TrpE of Salmonella typhimurium, conserved amino
      acid residues proven to be essential for inhibition of enzyme activity by L
      tryptophan were not present in Tk-TrpE. Namely, residues corresponding to Glu39,
      Met293, and Cys465 in the enzyme from S. typhimurium were replaced by Arg28,
      Thr221, and Ala384 in Tk-TrpE. Nevertheless, significant inhibition by L
      tryptophan was observed, with K(i) values of 5.25 and 74 microM for ammonia and
      glutamine-dependent activities, respectively. The inhibition was competitive with
      respect to chorismate. The results suggest that the amino acid residues involved
      in the feedback inhibition by L-tryptophan in the case of Tk-AS complex are
      distinct from previously reported anthranilate synthases.

PMID- 11237739
TI  - Transcriptional activation of p21(WAF1/CIP1) by apicidin, a novel histone
      deacetylase inhibitor.
AB  - Apicidin [cyclo(N-O-methyl-L-tryptophanyl-L-isoleucinyl-D-pipecolinyl-l-2-amino-8
      oxodecanoyl)], a novel histone deacetylase inhibitor, has been identified as an
      antiprotozoal and antiproliferative agent. In this study, we show apicidin
      induces transcriptional activation of p21(WAF1/CIP1) (p21) in human prostate
      carcinoma cells. Apicidin induces expression of p21 protein and mRNA and
      activation of p21 promoter-luciferase reporter constructs. Apicidin causes an
      accumulation of acetylated histones H3 and H4 in total cellular chromatin.
      Chromatin immunoprecipitation shows p21 promoter DNA is associated with
      hyperacetylated histones H3 and H4 after treatment with apicidin. Therefore, the
      data here demonstrate that apicidin activates p21 transcription associated with
      the acetylation of histones H3 and H4.

PMID- 11237740
TI  - Effect of benzo[a]pyrene diol epoxide on expression of retinoic acid receptor
      beta in immortalized esophageal epithelial cells and esophageal cancer cells.
AB  - Expression of retinoic acid receptor-beta (RAR-beta) is frequently lost in
      tobacco-related cancers. Benzo[a]pyrene diol epoxide (BPDE) is an active
      metabolite of tobacco procarcinogen benzo[a]pyrene and plays an important role in
      tobacco carcinogenesis. We therefore exposed SV-40 immortalized esophageal
      epithelial cells and esophageal cancer cells to BPDE to understand possible
      interactions between BPDE and RAR-beta expression. Our data showed that BPDE
      decreased RAR-beta mRNA and protein levels by suppression of transcription of RAR
      beta. Retinoic acid was able to partially block the inhibitory effect of BPDE on
      RAR-beta expression and to increase G1 phase of cell cycles. Furthermore,
      induction of COX-2 expression by BPDE was associated with RAR-beta inhibition.
      This study suggests that one way by which BPDE causes esophageal carcinogenesis
      may be through the inhibition of RAR-beta.

PMID- 11237741
TI  - Identification of a novel type I cytokine receptor CRL2 preferentially expressed
      by human dendritic cells and activated monocytes.
AB  - From a human dendritic cell (DC) cDNA library, we identified a novel type I
      cytokine receptor, designated as cytokine receptor-like molecule 2 (CRL2). CRL2
      cDNA encoded a 371-residue type I transmembrane protein with an extracellular
      domain of 210 residues and an intracellular domain of 119 residues. Its
      extracellular domain contains conserved cysteine residues and WAS-like motif in
      place of the hallmark of WSXWS motif present in other type I cytokine receptors.
      The intracellular domain contained a membrane-proximal "box 1" motif and
      conserved tyrosine residue potentially as a binding site for signal transducing
      molecules. CRL2 protein shares significant homology with common cytokine receptor
      (gammac) and interleukin-13 receptor alpha1 chain. Northern blot analysis showed
      that CRL2 was restrictedly expressed by spleen and peripheral blood leukocytes,
      and abundantly expressed by HL-60 cells. RT-PCR analysis demonstrated that CRL2
      was preferentially expressed by DC and monocytes. Interestingly, CRL2 expression
      was up-regulated when monocytes were activated by LPS. These indicate that CRL2
      may be involved in the biological functions of DC and monocytes. The Ba/F3
      transfectants of CRL2 was retrovirally established with the expressed FLAG-tagged
      CRL2 in the size of approximately 48 kD, which could be efficiently
      immunoprecipitated. We also prepared a CRL2Ig fusion protein. The identification
      of its ligand and involvement of signal transduction will help to elucidate its
      potential function.

PMID- 11237742
TI  - The F-box protein SKP2 binds to the phosphorylated threonine 380 in cyclin E and
      regulates ubiquitin-dependent degradation of cyclin E.
AB  - Cyclin E is required for S phase entry. The subsequent ubiquitin-dependent
      degradation of cyclin E contributes to an orderly progression of the S phase. It
      has been shown that phosphorylation of threonine 380 (Thr380) in cyclin E
      provides a signal for its ubiquitin-dependent proteolysis. We report that SKP2,
      an F-box protein and a substrate-targeting component of the SCF(SKP2) ubiquitin
      E3 ligase complex, mediates cyclin E degradation. In vitro, SKP2 specifically
      interacted with the cyclin E peptide containing the phosphorylated-Thr380 but not
      with a cognate nonphosphorylated peptide. In vivo, expression of SKP2 induced
      cyclin E polyubiquitination and degradation. Conversion of Thr380 into
      nonphosphorylatable amino acids caused significant resistance of cyclin E to
      SKP2. The presence of the CDK inhibitor p27(Kip1) also prevented the SKP2
      dependent degradation of cyclin E. Our findings suggest that SKP2 regulates
      cyclin E stability, thus contributing to the control of S phase progression.

PMID- 11237743
TI  - Glycated serum albumin-induced vascular smooth muscle cell proliferation through
      activation of the mitogen-activated protein kinase/extracellular signal-regulated
      kinase pathway by protein kinase C.
AB  - Proliferation of vascular smooth muscle cells (VSMC) contributes to the
      pathogenesis of atherosclerosis, and glycated serum albumin (GSA, Amadori adduct
      of albumin) might be a mitogen for VSMC proliferation, which may further be
      associated with diabetic vascular complications. In this study, we investigated
      the involvement of mitogen-activated protein kinase/extracellular signal
      regulated kinase (MAPK/ERK), and protein kinase C (PKC), in GSA-stimulated
      mitogenesis, as well as the functional relationship between these factors. VSMC
      stimulation with GSA resulted in a marked activation of ERK. The MAPK kinase
      (MEK) inhibitor, PD98059, blocked GSA-stimulated MAPK activation and resulted in
      an inhibition of GSA-stimulated VSMC proliferation. GSA also increased PKC
      activity in VSMC in a dose-dependent manner. The inhibition of PKC by the PKC
      inhibitors, GF109203X and Rottlerin (PKCdelta specific inhibitor), as well as PKC
      downregulation by phorbol 12-myristate 13-acetate (PMA), inhibited GSA-induced
      cell proliferation and blocked ERK activation. This indicates that phorbol ester
      sensitive PKC isoforms including PKCdelta are involved in MAPK activation. Thus,
      we show that the MAPK cascade is required for GSA-induced proliferation, and that
      phorbol ester-sensitive PKC isoforms contribute to cell activation and
      proliferation in GSA-stimulated VSMC.

PMID- 11237744
TI  - Synergistic activation of RSK correlates with c-fos induction in MO7e cells
      stimulated with GM-CSF plus Steel factor.
AB  - Steel factor (SLF) plus GM-CSF induces proliferative synergy in factor-dependent
      cell line MO7e and hematopoietic progenitor cells. We previously reported ERK1/2
      involvement in this synergy, but its downstream signaling molecules are not
      defined. Here, we investigated activation of the 90-kDa ribosomal S6 kinase (RSK)
      proteins by measuring the phosphorylation status and in vitro kinase activity in
      MO7e cells. Both GM-CSF and SLF induced activation of RSK, and the combined
      stimulation with these two cytokines induced synergistic and persistent
      activation of RSK. RSK activity was reduced by PI3 kinase inhibitor LY294002 or
      MEK1 inhibitor PD98059, suggesting that the ERK as well as the PI3 kinase
      pathways are involved in regulation of RSK activity. Sensitivities of RSK
      activity to inhibitory drugs correlated well with those of c-fos gene induction.
      Taken together, synergistic activation of RSK may contribute, at least in part,
      to the synergistic induction of c-fos after combined stimulation with GM-CSF plus
      SLF.

PMID- 11237745
TI  - Inhibition of preadipocyte differentiation by myostatin treatment in 3T3-L1
      cultures.
AB  - Myostatin, a new TGF-beta family member, is known as a muscle growth inhibitor,
      but its role in adipocyte development has not been studied. To test the role of
      Myostatin in 3T3-L1 preadipocyte differentiation, we treated cultured 3T3-L1
      preadipocytes with Myostatin dissolved in 0.1% trifluoroacetic acid (TFA) during
      differentiation after they had become confluent. Myostatin treatment
      significantly decreased glycerol-3-phosphate dehydrogenase (GPDH) activity and
      oil Red-O staining compared to controls that did not receive Myostatin. Western
      blot analysis showed that the expression levels of CCAAT/enhancer binding protein
      alpha (C/EBP alpha) and peroxisome proliferator-activated receptor gamma (PPAR
      gamma) were significantly decreased by Myostatin treatment (P < 0.05). However,
      the expression of C/EBP beta was not significantly changed by the treatment (P >
      0.05). From RT-PCR result, the relative level of leptin mRNA in Myostatin-treated
      cells was not significantly different (P > 0.1) from the level in cells without
      Myostatin treatment. Our data show that Myostatin, a secreted protein from
      muscle, inhibits preadipocyte differentiation in 3T3-L1 cells, which is mediated,
      in part, by altered regulation of C/EBP alpha and PPAR gamma.

PMID- 11237746
TI  - Differential expression of signal transducers and activators of transcription
      during human adipogenesis.
AB  - Signal Transducers and Activators of Transcription (STATs) display unique
      expression patterns upon induction of differentiation of murine 3T3-L1
      preadipocytes into adipocytes. During differentiation, expression of STAT1 and
      STAT5 increase, while STAT3 and STAT6 remain relatively unchanged. Here, we
      determined whether human subcutaneous preadipocytes expressed STATs and if the
      pattern of expression changed during adipogenesis. We found by Western blot
      analysis that freshly isolated preadipocytes expressed STAT1, STAT3, STAT5, and
      STAT6, but not STAT2 and STAT4. Induction of preadipocyte differentiation with 1
      methyl-3-isobutylxanthine, dexamethasone, insulin, and BRL49653 decreased
      expression of STAT1, and increased expression of STAT3 and STAT5. STAT6
      expression did not change during adipogenesis. Changes in expression of
      CCAAT/enhancer binding protein beta (C/EBPbeta), C/EBPdelta, C/EBPalpha, and
      peroxisome proliferator-activated receptor gamma were similar to murine cell
      lines. These results suggest that unlike the traditional adipogenic transcription
      factors, unique differences exist in STAT expression patterns between murine and
      human adipose cells.

PMID- 11237747
TI  - Regulation of the nuclear orphan receptor Nur77 in bone by parathyroid hormone.
AB  - Osteoblasts function under the control of several hormones and growth factors.
      Among them, parathyroid hormone (PTH) and steroid hormones have significant
      effects on bone metabolism. We show that PTH induced the expression of Nur77, a
      member of the NGFI-B subfamily of nuclear orphan receptors in bone. PTH rapidly
      and transiently induced Nur77 mRNA in primary mouse osteoblasts that peaked at 1
      h and at 10 nM of hormone. Cycloheximide did not affect the induction of Nur77
      mRNA, suggesting that protein synthesis is not required for the PTH effect. PTH
      also induced Nur77 mRNA in calvariae cultures. Finally Nur77 protein expression
      was induced in nuclear protein extracts of cells treated with PTH. NGFI-B nuclear
      receptors have been implicated in retinoic acid, vitamin D, and thyroid hormone
      signaling. We propose that induction of NGFI-B nuclear orphan receptors
      represents a potential cross-talk mechanism between PTH and steroid hormone
      signaling to regulate bone metabolism.

PMID- 11237748
TI  - Control of the cystic fibrosis transmembrane conductance regulator by alphaG(i)
      and RGS proteins.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) has been shown
      previously to be regulated by inhibitory G proteins. In the present study, we
      demonstrate inhibition of CFTR by alphaG(i2) and alphaG(i1), but not alphaG(0),
      in Xenopus oocytes. We further examined whether regulators of G protein signaling
      (RGS) proteins interfere with alphaG(i)-dependent inhibition of CFTR. Activation
      of CFTR by IBMX and forskolin was attenuated in the presence of alphaG(i2),
      indicating inhibition of CFTR by alphaG(i2) in Xenopus oocytes. Coexpression of
      the proteins RGS3 and RGS7 together with CFTR and alphaG(i2) partially recovered
      activation by IBMX/forskolin. 14-3-3, a protein that is known to interfere with
      RGS proteins, counteracted the effects of RGS3. These data demonstrate the
      regulation of CFTR by alphaG(i) in Xenopus oocytes. Because RGS proteins
      interfere with the G protein-dependent regulation of CFTR, this may offer new
      potential pathways for pharmacological intervention in cystic fibrosis.

PMID- 11237749
TI  - Interaction of the N-terminal part of the A1 essential light chain with the
      myosin heavy chain.
AB  - The kinetics of actin-dependent MgATPase activity of skeletal muscle myosin
      subfragment 1 (S1) isoform containing the A1 essential light chain differ from
      those of the S1 isoform containing the A2 essential light chain. The differences
      are due to the presence of the extra N-terminal peptide comprising 42 amino acid
      residues in the A1 light chain. This peptide can interact with actin; heretofore,
      there have no been reports of the direct interaction between this peptide and the
      heavy chain of S1. Here, using the zero-length cross-linker 1-ethyl-3-(3
      dimethylaminopropyl)carbodiimide (EDC) and S. aureus V8 protease, we show for the
      first time that the N-terminal part of the A1-light chain can interact with the
      22-kDa fragment of the S1 heavy chain. No such interaction has been observed for
      the S1(A2) isoenzyme. Localization of residues which can possibly react with the
      cross-linker suggests that the interaction might involve the N-terminal residues
      of the A1 light chain and the converter region of the heavy chain.

PMID- 11237750
TI  - Pilot study to determine the feasibility of producing protease-resistant prion
      protein fragments by random PCR mutagenesis.
AB  - We report the results of a pilot study to determine the feasibility of using PCR
      random mutagenesis and in vitro transcription/translation to produce protease
      resistant full-length or truncated ovine prion proteins (PrP). Using this
      approach, we show the novel production of protease resistant recombinant ovine
      prion protein fragments isolated from a panel of seventy randomly mutated ovine
      PrP protein molecules. Protease resistance of the proteinase K (PK) digested
      fragments was present de novo within physiological conditions without the need
      for template-assisted conversion to protease resistance or the requirement of
      reductants, denaturants or acid pH reported to date. Four of the mutant proteins
      were truncated at their C-termini and all of these gave rise to digestion
      products which were protease resistant at significant PK concentrations and
      exposure times. All other mutant proteins translated as full length molecules and
      gave rise to PK-resistant products which showed a variability in their proteinase
      digestion profiles. We discuss the relevance of these finding to current
      research.

PMID- 11237751
TI  - Gene cloning of immunogenic antigens overexpressed in pancreatic cancer.
AB  - The serological analysis of recombinant cDNA expression libraries (SEREX) by
      utilizing a library derived from a human pancreatic adenocarcinoma cell line and
      IgG antibodies from an allogeneic patient serum led to the identification of 18
      genes: 13 of these were known genes, and 5 were unknown genes. In Northern and RT
      PCR analyses, we found that the expression of mRNA of 14 genes was elevated in
      pancreatic cancer cell lines compared with the levels in normal pancreatic
      tissues. In addition, the expression of mRNA of hsp105 in colon cancer was
      greater than that in normal colon tissue. Immunohistochemical analysis using anti
      hsp105 antibody revealed that an increased expression of hsp105 is a
      characteristic feature of pancreatic ductal and colon adenocarcinoma.
      Furthermore, hsp105 immunoreactivity in some cases of gastric, esophageal, and
      hepatocellular carcinoma was much stronger than that in normal corresponding
      tissues. These molecules identified may provide good diagnostic markers for
      cancer cells.

PMID- 11237752
TI  - c-myc activation in early coronary lesions in experimental hypercholesterolemia.
AB  - This study tested the hypothesis that c-Myc activation, an oxidation-sensitive
      transcription factor, and its binding partner Max occurs in coronary arteries of
      hypercholesterolemic (HC) pigs, and can be attenuated by chronic antioxidant
      intervention. Coronary arteries were isolated from normal, HC pigs, or HC
      supplemented with antioxidant vitamins (HC + vitamins). The expression of the c
      Myc/Max complex, and its target genes GADD45 and p53, was studied in
      nonatherosclerotic, early lesions (LL), positively staining for oil-red-O, in
      adjacent lesion-prone regions (PL), and in healthy segments (HV). The expression
      of c-Myc and Max in HC was 2- to 3-fold greater in PL, and 4-fold in LL, compared
      to normal vessels (P < 0.01). The expression of GADD45 was down-regulated, and of
      p53 increased, in the same regions. These alterations were attenuated in the HC +
      vitamins. Thus, c-Myc activation is an early atherosclerosis, in both PL and LL
      coronary arterial regions, and can be blunted by chronic dietary antioxidant
      intervention.

PMID- 11237754
TI  - Streptococcus mutans lipoteichoic acid-induced apoptosis in cultured dental pulp
      cells from human deciduous teeth.
AB  - Herein, we suggest that Streptococcus mutans lipoteichoic acid-induced death of
      dental pulp cells on human deciduous teeth is caused by apoptosis. We provide
      evidence for the causal role of apoptosis in this process by demonstrating an
      increase in the proportion of fragmented DNA in such dental pulp cells, which
      results in a ladder pattern of DNA fragmentation. Additionally, Streptococcus
      mutans lipoteichoic acid-induced apoptotic cell death is suppressed by caspase
      inhibitor. Collectively, these findings suggest that Streptococcus mutans
      lipoteichoic acids may cause apoptosis in human dental pulp cells, and serve as
      an important factor in pulpitis.

PMID- 11237753
TI  - Fudenine, a C-terminal truncated rat homologue of mouse prominin, is blood
      glucose-regulated and can up-regulate the expression of GAPDH.
AB  - Messenger RNA differential display was applied to screen for the blood glucose
      regulated genes in SD rat skeletal muscle. The rat homologue of the mouse
      prominin was thus identified. Comparing to its mouse and human homologues,
      fudenine was C-terminal truncated due to a single nucleotide deletion. However,
      its mitochondrial energy transfer signature peptide PQDLVKKLI remained intact.
      Fudenine, an 592-amino acid containing, 66-kDa glycoprotein, is a novel plasma
      membrane protein with four transmembrane segments flanking by two large
      glycosylated extracellular domains. Although it is devoid of the last
      transmembrane domain comparing to its homologues, fudenine also locates in cell
      membrane by transfection of fusion plasmid pFudenine-EGFP into CBRH7919 cell and
      L-6TG cell. Overexpression of fudenine in CBRH7919 cell line up-regulated the
      mRNA level of GAPDH (3-phosphate glyceraldehyde dehydrogenase), while long-term
      glucose exposure resulted to reduced GAPDH expression. Since high blood glucose
      level induced the expression of fudenine in skeletal muscle, which in turn up
      regulated the expression of GAPDH, we propose that fudenine might be a candidate
      gene for diabetes mellitus.

PMID- 11237755
TI  - Assembly of truncated HCV core antigen into virus-like particles in Escherichia
      coli.
AB  - Core protein is one of the most conserved and immunogenic of the hepatitis C
      virus proteins. Several pieces of experimental evidence suggest its ability for
      formation of virus like particles alone or in association with other viral
      proteins in mammalian or yeast cells with great similarity to those detected in
      patient sera and liver extract. In this work we report an Escherichia coli
      derived truncated hepatitis C core protein that is able to aggregate. SDS-PAGE
      and size exclusion chromatography patterns bring to mind the aggregation of
      monomers of recombinant protein Co.120. The Co.120 protein migrated with buoyant
      density of 1.28 g/cm(3) when analyzed using CsCl density gradient centrifugation.
      Spherical structures with an average diameter of 30 nm were observed using
      electron microscopy. We report here that VLPs are generated when the first 120 aa
      of HCV core protein are expressed in E. coli.

PMID- 11237756
TI  - Functional studies on the Wilson copper P-type ATPase and toxic milk mouse
      mutant.
AB  - The Wilson protein (WND; ATP7B) is an essential component of copper homeostasis.
      Mutations in the ATP7B gene result in Wilson disease, which is characterised by
      hepatotoxicity and neurological disturbances. In this paper, we provide the first
      direct biochemical evidence that the WND protein functions as a copper
      translocating P-type ATPase in mammalian cells. Importantly, we have shown that
      the mutation of the conserved Met1386 to Val, in the Atp7B for the mouse model of
      Wilson disease, toxic milk (tx), caused a loss of Cu-translocating activity.
      These investigations provide strong evidence that the toxic milk mouse is a valid
      model for Wilson disease and demonstrate a link between the loss of catalytic
      function of WND and the Wilson disease phenotype.

PMID- 11237757
TI  - De novo synthesis and recycling pathways of sphingomyelin in rat Sertoli cells.
AB  - Sertoli cells from 19-day-old rats have two molecular species of sphingomyelin
      (SM1 and SM2) with different kinetic characteristics and fatty acid composition.
      Here, we have studied the incorporation of [14C]-choline and [14C]-palmitic acid
      into SM in presence or absence of fumonisin B1, an inhibitor of ceramide
      synthesis, and beta-chloroalanine, an inhibitor of sphinganine synthesis. The
      contributions of de novo synthesis and recycling pathways were estimated by
      analysis of the inhibition caused by these drugs. SM1 was synthesized more by
      sphingosine recycling, and SM2 was synthesized principally by ceramide recycling
      than SM1. De novo synthesis seems to be important for the two SM types, but our
      results showed that this pathway is more extensively utilized by SM2. In
      conclusion, using Sertoli cell cultures, we have shown for the first time that in
      the same cell different molecular species of SM are synthesized by different
      pathways.

PMID- 11237758
TI  - New method for analyzing the molecular weights of proteins by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis.
AB  - Previously the method for determining protein molecular weights from SDS-PAGE
      depended on the accidental, only partial linearity of protein movement with the
      logarithm of its molecular weight. A new, mathematically rigorous method with
      supporting data is now described demonstrating that such movement is dependent
      upon the reciprocal of protein size. Experimental data, therefore, follow most
      closely a hyperbolic curve when plotted directly; it becomes linear and passes
      through the origin when movement is plotted vs the reciprocal of protein
      molecular weight. In the earlier method determination of the error of a
      measurement of molecular weight is very complex and never determined. In the
      method presented here such error is easily estimated and it is identical in both
      the hyperbolic and linear forms of data presentation. This method may eventually
      also allow other less-significant forces controlling movement such as protein
      charge to be analyzed and understood.

PMID- 11237759
TI  - FKBP binding characteristics of cardiac microsomes from diverse vertebrates.
AB  - FK506 binding protein (FKBP) is a cytosolic receptor for the immunosuppressive
      drug FK-506. The common isoform, FKBP12, was found to be associated with the
      calcium release channel (ryanodine receptor 1) of different species of vertebrate
      skeletal muscle, whereas 12.6, a novel FKBP isoform was found to be associated
      with canine cardiac ryanodine receptor (ryanodine receptor 2). Until recently,
      canine cardiac sarcoplasmic reticulum was considered to be the prototype for
      studying heart RyR2 and its interactions with FKBP. In this study, cardiac
      microsomes were isolated from diverse vertebrates: human, rabbit, rat, mice, dog,
      chicken, frog, and fish and were analyzed for their ability to bind or exchange
      with FKBP isoforms 12 and 12.6. Our studies indicate that RyR2 from seven out of
      the eight animals contain both FKBP12 and 12.6. Dog is the exception. It can now
      be concluded that the association of FKBP isoforms with RyR2 is widely conserved
      in the hearts of different species of vertebrates.

PMID- 11237760
TI  - NF-kappaB blockade reduces the O2-evoked rise in Na+ conductance in fetal
      alveolar cells.
AB  - Electrophoretic mobility shift assays revealed minimal levels of NF-kappaB
      activity in rat distal lung epithelial cells cultured at fetal (23 mmHg) or adult
      alveolar (100 mmHg) P(O2), but revealed significant activation of this
      transcription factor in cells exposed to a rise in P(O2) mimicking that
      experienced at birth. This response was entirely abolished by pretreating cells
      with 5 mM sulfasalazine (SSA). This shift in P(O2) also evoked a rise in apical
      Na+ conductance (G(Na+)) that may underlie the O2-evoked stimulation of Na+
      transport seen in these cells. Pretreatment with SSA had no effect upon G(Na+) in
      cells cultured continually at adult or fetal P(O2) but did inhibit the increase
      in G(Na+) seen in cells that had experienced the rise in P(O2). O2-evoked
      activation of NF-kappaB may thus mediate the increased Na+ transport that occurs
      when the distal lung epithelial cells are exposed to a physiologically-relevant
      increase in P(O2).

PMID- 11237762
TI  - Species-specific interaction of transcription factor p70 with the rDNA core
      promoter.
AB  - p70 is a transcription factor that is involved in the initiation of transcription
      by RNA polymerase I and has been shown to cooperate with the selectivity factor
      SL1 for binding to the core promoter region of mammalian ribosomal RNA gene
      (rDNA). To examine a role of the p70-SL1 interaction in promoter recognition,
      mouse and human proteins were partially purified and analyzed by UV-cross
      linking. Mouse rDNA core promoter was recognized by any combination of p70 and
      SL1 prepared from either species. In contrast, human p70 no longer bound to the
      human core promoter when mouse SL1 was used. Thus, a species-specific interaction
      between p70 and SL1 may be involved in the promoter selection for rDNA
      transcription.

PMID- 11237761
TI  - Metabolic biotinylation of secreted and cell surface proteins from mammalian
      cells.
AB  - Due to its strength and specificity, the interaction between avidin and biotin
      has been used in a variety of medical and scientific applications ranging from
      drug targeting to immunohistochemistry. To maximize the application of this
      technology in mammalian systems, we recently demonstrated the ability to
      metabolically biotinylate tagged proteins in mammalian cells using the endogenous
      biotin ligase enzymes of the mammalian cell. This technology allows site-specific
      biotinylation without any exogenous reagents and eliminates possible inactivation
      of the protein of interest by nonspecific biotinylation. Here, we report further
      expansion of the mammalian metabolic biotinylation technology to enable
      biotinylation of proteins secreted from mammalian cells and expressed on their
      cell surface by cosecretion with BirA, the biotin ligase of E. coli. This
      technique can be used to biotinylate secreted proteins for purification or
      targeting and also for biotinylating the surfaces of mammalian cells to
      facilitate their labeling and purification from other nontagged cells.

PMID- 11237763
TI  - Human RNA helicase II/Gu gene: genomic organization and promoter analysis.
AB  - Human RNA helicase II/Gu (hRH II/Gu) protein unwinds double-stranded RNA, folds
      single-stranded RNA, and may play important roles in ribosomal RNA biogenesis,
      RNA editing, RNA transport, and general transcription. The genomic organization
      and the regulation of expression of the hRH II/Gu gene were analyzed. The hRH
      II/Gu gene is over 29 kb in length, and includes 15 exons. All intron-exon
      junctions contain consensus GT-AG sequences. An 85 bp basic promoter was
      identified which lacks a functional TATA box. In LNCaP cells, the hRH II/Gu
      promoter was up to 50 times as active as pGL2-control vector which has an SV 40
      early promoter. Mutation of a putative c-Myc/USF binding site in the region
      between -110 and -85 caused a decrease in the promoter activity by 2- to 3-fold.
      A negative regulatory region was also found between -324 and -264. Studies of
      transcriptional regulation of hRH II/Gu under different physiological and
      pathophysiological conditions may provide clues to its biological function.

PMID- 11237764
TI  - Fibrinogenolytic proteases isolated from the snake venom of Taiwan habu: serine
      proteases with kallikrein-like and angiotensin-degrading activities.
AB  - Two venom proteases with fibrinogenolytic activity were isolated from the venom
      of Taiwan habu (Trimeresurus mucrosquamatus), one major crotalid snake species in
      Taiwan. The purified enzymes showed a strong beta-fibrinogenolytic activity,
      cleaving the beta-chain of fibrinogen molecules specifically. They also showed
      strong kallikrein-like activity in vitro, releasing bradykinin from kininogen.
      The purified enzymes did not coagulate human plasma, yet decreasing fibrinogen
      levels in plasma and prolonging bleeding without formation of fibrin clots,
      indicating that both proteases have specificities different from thrombin and the
      thrombin-like proteases of snake venom reported previously. They also exhibit
      amidase activity against N-benzoyl-Pro-Phe-Arg-p-nitroanilide, which is a
      specific synthetic substrate for kallikrein-like proteases. Their stability at
      high temperatures was examined and found to be more stable when compared with
      ancrod and thrombin. Intravenous injection of either protease was shown to lower
      blood pressure in experimental rats. Most noteworthy is the observation that the
      proteases can cleave angiotensin I and release bradykinin from plasma kininogen
      in vitro, which is a strong vasodilator and probably responsible for the in vivo
      hypotensive effect of these venom proteases.

PMID- 11237766
TI  - Mutations affecting the calcium-binding site of myeloperoxidase and
      lactoperoxidase.
AB  - Both myeloperoxidase (MPO) and lactoperoxidase (LPO) contain high affinity bound
      calcium, which has been suggested to play a structural role. Asp-96 in MPO, a
      residue next to the histidine distal from the heme prosthetic group, has been
      assigned to the calcium-binding site of the enzyme by X-ray crystallography.
      Multiple sequence alignment of known animal peroxidases has revealed that the
      calcium-binding site is highly conserved. In this study, we replaced Asp-96 in
      MPO and the counterpart Asp-227 in LPO both with Ala by site-directed
      mutagenesis. The level of peroxidase activity in insect cells infected with
      recombinant baculoviruses and their culture supernatants was reduced to virtually
      zero as a result of these mutations. Immunoblotting revealed that these mutant
      peroxidases were expressed in the cells but not secreted as effectively as the
      wild-type enzymes. Our findings suggest that a functional calcium-binding site is
      essential for the biosynthesis of active animal peroxidases.

PMID- 11237765
TI  - Involvement of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase
      in alpha1B-adrenergic receptor/Galphaq-induced inhibition of cell proliferation.
AB  - Certain G protein-coupled receptors (GPCRs) stimulate the activities of c-Jun N
      terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), members of
      the MAPK family. We investigated the role of JNK and p38 MAPK activation induced
      by the alpha1B-adrenergic receptor in the proliferation of human embryonic kidney
      293T cells. Activation of the alpha1B-adrenergic receptor resulted in inhibition
      of cell proliferation. This receptor-induced inhibition of proliferation was
      blocked by a kinase-deficient MKK4 and by the p38 MAPK inhibitor SB203580.
      Additionally, transfection of constitutively activated Galphaq into cells also
      led to inhibition of proliferation in a JNK- and p38 MAPK-dependent manner. These
      results demonstrate that the alpha1B-adrenergic receptor/Galphaq signaling
      inhibits cell proliferation through pathways involving JNK and p38 MAPK.

PMID- 11237767
TI  - Identification of a novel inhibitor of LPS-induced TNF-alpha production with
      antiproliferative activity in monocyte/macrophages.
AB  - An isoquinoline derivative, 5-methyl-7,8-dimethoxy-1-phenylpyrazolo[5,4
      c]isoquinoline (compound 1), was identified as a novel inhibitor of LPS-induced
      TNF-alpha production by cell-based screening. Compound 1 suppressed LPS-induced
      TNF-alpha production in RAW264.7 cells and murine peritoneal macrophages in a
      dose-dependent manner similar to SB203580, known as a specific inhibitor of p38
      MAPK. It also inhibited an LPS-induced increase in serum TNF-alpha in a mouse
      endotoxic shock model with an ED(50) of approximately 10 mg/kg. Compound 1 had
      little effect on the incorporation of [3H]-leucine into the cells, while it
      suppressed LPS-induced TNF-alpha mRNA levels in RAW264.7 cells. The results
      indicate that suppression of TNF-alpha production was not a result of nonspecific
      inhibition of de novo translation but was based on the decreased TNF-alpha mRNA
      levels. The in vitro kinase assay revealed that compound 1 did not strongly
      inhibit p38 MAPK activity, its potency being much lower than that of SB203580,
      suggesting that the TNF-alpha-suppressive action of compound 1 cannot be
      attributed to the inhibition of p38 MAPK. Furthermore, in contrast to SB203580,
      it significantly inhibited the growth of RAW264.7 and THP-1 cells in a cytostatic
      manner. Compound 1 is likely to have antiinflammatory and antiproliferative
      effects by acting on some molecule other than p38 MAPK that contributes to both
      LPS-induced TNF-alpha production and the cell growth of monocyte/macrophages.

PMID- 11237768
TI  - Loss of calcineurin from the medial preoptic area of primiparous rats.
AB  - Western blot analyses reveal that calcineurin A (CNA), which is present in the
      hippocampus, basolateral amygdala, parietal cortex, and MPOA of virgin males and
      females, is undetectable only in the MPOA of primiparous females regardless of
      whether they had postpartum pup contact or not. In contrast, CNB was expressed at
      unchanging levels in the PC and MPOA. Similarly, G(alphao) and PKA(RI) were
      expressed at high levels in all of the brain regions of virgin males, virgin
      females, and primiparous females, supporting the concept that this loss of CNA is
      a specific event. Understanding how and why the expression of CNA, the sole
      neuronal Ca2+/CaM-dependent protein phosphatase, is down-regulated specifically
      in the MPOA of primiparous females may yield some insight into the signal
      transduction events that mediate the onset of mammalian maternal behavior.

PMID- 11237769
TI  - Expression of the Hoxa-13 gene correlates to hepatitis B and C virus associated
      HCC.
AB  - To study the Hoxa-13 gene in the liver, we examined its expression by RT-PCR in
      various liver cell lines, rat livers under different conditions, and human
      primary hepatocellular carcinomas (HCCs). The gene was found to be expressed in
      cell lines originating from liver stem-like cells, but not in cell lines
      originating from hepatocytes and bile duct epithelia. Expression was induced in
      rat livers after treatment with d-galactosamine, which is known to induce oval
      cell proliferation, but not after a two-thirds partial hepatectomy (2/3 PH) where
      induction of oval cell proliferation is thought not to occur. Expression of the
      gene correlated with human HCC samples associated with Hepatitis B or C virus
      infection in this small series. These results suggest that the Hoxa-13 gene may
      provide a potentially useful tool for elucidation of mechanisms involved in
      lineage-specific differentiation and carcinogenesis of liver stem cells.

PMID- 11237770
TI  - A new member of the sorting nexin family interacts with the C-terminus of P
      selectin.
AB  - P-selectin is a cell adhesion molecule found in platelets and endothelial cells
      mediating binding of leukocytes. It is stored in secretory granules and expressed
      at the plasma membrane after cell activation. After rapid internalisation P
      selectin recycles or is degraded. The 35 amino acid cytoplasmic domain of P
      selectin contains signals for sorting into secretory granules, for endocytosis
      and for delivery to lysosomes. To investigate protein-protein interactions, we
      performed two-hybrid screening using the cytoplasmic domain of P-selectin as
      bait. KIAA0064 was identified as a putative intracellular P-selectin binding
      protein. Because the protein contains a phox homology (PX) domain in the N
      terminus which is a characteristic feature of the sorting nexin (SNX) family, it
      was named SNX17. The PX domain is not required for binding of P-selectin in the
      two-hybrid system. Expression of a fusion protein between SNX17 and green
      fluorescent protein demonstrated localisation of SNX17 in the cytosol and to
      membranes.

PMID- 11237771
TI  - Amphiregulin is a vitamin D3 target gene in squamous cell and breast carcinoma.
AB  - 1alpha,25-Dihydroxyvitamin D(3) [1,25(OH)2D3] inhibits growth of cells derived
      from a variety of tumors in vitro and in vivo. Proliferation in vitro of human
      SCC25 cells, derived from a primary squamous cell carcinoma (SCC) of the tongue,
      was blocked by 1,25(OH)2D3 and its analog EB1089. A similar effect was observed
      with 13-cis retinoic acid (RA), which has been used in chemoprevention of SCC. We
      identified amphiregulin, a member of the epidermal growth factor family, as a
      1,25(OH)2D3 target gene in SCC25 cells. Induction of amphiregulin mRNA by
      1,25(OH)2D3 was rapid and sustained over 48 h, and was unaffected by
      cycloheximide. 1,25(OH)2D3 also induced amphiregulin mRNA in estrogen receptor
      positive and -negative human breast cancer cell lines, but not in LNCaP human
      prostate cancer cells. RAR- or RXR-specific retinoids did not affect amphiregulin
      mRNA levels in SCC25 cells; however, 13-cis RA partially blocked the response to
      1,25(OH)2D3. Amphiregulin partially inhibited growth of SCC25 cells in culture.
      Our data show that amphiregulin is a 1,25(OH)2D3 target gene, and suggest that
      its induction may contribute to the growth inhibitory effects of 1,25(OH)2D3.

PMID- 11237772
TI  - Cloning of hypoxia-inducible factor 1alpha cDNA from chick embryonic ventricular
      myocytes.
AB  - Hypoxia-inducible factor 1 (HIF-1) is composed of HIF-1alpha and arylhydrocarbon
      nuclear receptor translocator (ARNT), which belong to the basic-helix-loop-helix
      Per/ARNT/Sim (bHLH-PAS) family of transcription factors. HIF plays key roles in
      oxygen homeostasis and embryonic cardiovascular development. In this study, we
      have cloned cDNAs encoding the chick HIF-1alpha from cultured embryonic
      ventricular myocytes (CEVM) and then examined its expression in various embryonic
      tissues. The deduced amino acid sequence of the chick HIF-1alpha cDNA showed 79%
      identity with that of the human HIF-1alpha cDNA. In contrast, sequence homology
      between the chick HIF-1alpha and endothelial PAS protein 1 (EPAS1), another
      member of the bHLH-PAS proteins, was only low (49%). HIF-1alpha mRNA was
      expressed abundantly in CEVM, but scarcely in the liver, which was quite
      different from expression pattern of EPAS1 mRNA. These data suggest that HIF
      1alpha may be involved in embryonic cardiovascular development. HIF-1alpha and
      EPAS1 may play distinct roles during developmental stages.

PMID- 11237773
TI  - Pregnancy and radiation.
AB  - The risk of foetal irradiation during pregnancy is discussed. It seems that, due
      to the low level of X-ray exposure to the foetus, neither diagnostic radiography
      nor nuclear diagnostic examination justifies termination of pregnancy.
      Radiotherapy for breast cancer, Hodgkin's disease and cervical cancer in pregnant
      women is reviewed. Radiation therapy for breast cancer is not an absolute
      contraindication for pregnancy and the risk-benefit assessment should be
      discussed with the mother. The risk to the foetus during radiotherapy for
      supradiaphragmatic Hodgkin's disease appears to be minimal, provided special
      attention is paid to the treatment techniques and the foetus is adequately
      shielded. Radiotherapy for the treatment of cervical cancer may be necessary
      during pregnancy, but the timing should be adjusted taking into consideration
      gestational age. Offspring of cancer patients who were treated by radiotherapy
      appear to be at little risk of childhood cancer or birth defects. Cancer patients
      should not be discouraged from having children and can expect a good outcome of
      pregnancy. However, in the non-pregnant woman, to further reduce any risk it is
      advisable to delay pregnancy for 12 months following completion of radiation
      therapy.

PMID- 11237774
TI  - Paget's disease of the breast.
AB  - Paget's disease of the breast is a rare disorder of the nipple-areola complex
      that is often associated with an underlying in situ or invasive carcinoma. A
      change in sensation of the nipple-areola, such as itching and burning, is a
      common presenting symptom. Objectively, eczematoid changes of the nipple-areola
      complex are common. The later stages of Paget's disease of the breast are
      characterized by ulceration and destruction of the nipple-areola complex.
      Eczematoid changes of the nipple-areola complex and persisting soreness or
      itching, without obvious reason, is a suspicious symptom for Paget's disease of
      the breast and calls for thorough evaluation, including mammography. Exfoliative
      cytology with demonstration of Paget's cells may be useful, but a negative
      finding does not exclude Paget's disease of the breast. Surgical biopsy is the
      diagnostic standard and therefore the diagnosis should always be confirmed by
      open (surgical) biopsy. The histogenesis of Paget's disease of the breast
      continues to be debated. The epidermotropic theory holds that Paget's cells are
      ductal carcinoma cells that have migrated from the underlying breast parenchyma
      to the nipple epidermis. According to the in situ transformation theory, the
      Paget's cells arise as malignant cells in the nipple epidermis independent from
      any other pathologic process within the breast parenchyma. This theory has been
      proposed to explain those cases in which there is no underlying mammary carcinoma
      or when there is a carcinoma remote from the nipple-areola complex. Each of these
      theories is plausible; however, treatment approaches differ markedly depending on
      the theory of histogenesis. Mastectomy has been considered the standard of care
      in the management of patients with Paget's disease of the breast. Nowadays,
      however, some patients with Paget's disease of the breast are candidates for
      breast-conserving therapy. Patients must be selected carefully on an individual
      basis. Until there is a better understanding of the relationship of Paget's
      disease of the breast to the underlying cancer the surgeon should understand the
      natural history and behaviour of this lesion and be aware of both the risks of
      under- and over-treating patients with Paget's disease of the breast.

PMID- 11237775
TI  - Postoperative irradiation in endometrial cancer: still a matter of controversy.
AB  - Although endometrial cancer is the most common female malignancy, evidence-based
      uniform guidelines for postoperative therapy have not been established. The most
      logical management is adjuvant irradiation tailored to the extent of surgery, the
      tumour grade, depth of myometrial invasion, degree of lymph node involvement and
      age of the patient. Currently, the only widely accepted treatment recommendations
      are no further therapy in low-risk patients who underwent extensive surgical
      staging, and external beam radiotherapy (EBRT) in high-risk patients. Most
      authors recommend postoperative application of only one radiotherapy modality:
      either brachytherapy (BRT) or EBRT, as their routine combination does not clearly
      improve the outcome but does increase the risk of late complications. A
      combination of BRT and EBRT should however be considered in patients with stage
      II disease, for infiltration of the lower uterine segment, vaginal involvement,
      positive or close surgical margins, capillary space involvement or unfavourable
      histology. Two recent randomized studies including mostly intermediate-risk
      patients managed with either extensive surgical staging or total abdominal
      hysterectomy and bilateral salpingo-oophorectomy (TAH&BSO) with or without
      postoperative EBRT, showed better local control but no survival benefit from
      adjuvant irradiation. Two ongoing Gynecologic Oncology Group (GOG) studies
      compare adjuvant chemotherapy with pelvic or abdominal irradiation in patients
      with high risk of local relapse. The role of adjuvant radiotherapy (EBRT with or
      without BRT) in high-risk patients as well as the value of lymphadenectomy in
      patients fit for such surgery is being addressed in a trial co-ordinated by the
      Medical Research Council. Future studies are warranted to define whether any
      irradiation should be employed in intermediate-risk patients and which
      radiotherapy modality should be used in high-risk node-negative patients with
      stage I tumours (stage Ib grade 3 and all stage Ic). Other issues which should be
      addressed in future studies include the extent of surgery, the role of systemic
      therapies, the relevance of novel biologic prognostic factors, salvage therapies
      after recurrence, cost-benefit analysis and quality of life.

PMID- 11237776
TI  - Mitomycin C: a clinical update.
AB  - Mitomycin C was reviewed in this journal 25 years ago and an update of its
      clinical usefulness is appropriate. The current review is based on representative
      publications covering clinical trials performed throughout the world. Single
      agent activity in each of the major neoplastic diseases has been reassessed when
      possible and the most important combinations evaluated. It is concluded that
      mitomycin C has a definite place in the treatment of localized bladder cancer, is
      active, but needs to be redefined, in the context of newer regimens for breast,
      head and neck, and non-small cell lung cancers, is active in, but is being
      displaced by, other drugs in cervical, gastric and pancreatic cancers, and is
      probably no longer of therapeutic value in colon cancer. It is also recognized
      that as many newer treatments have clinical success, the therapeutic role of
      mitomycin C will require continuing re-investigation.

PMID- 11237777
TI  - The use of anti-inflammatory drugs in cancer pain.
AB  - The role of non-steroidal anti-inflammatory drugs (NSAIDs) in cancer pain has
      been well established in the treatment of mild pain and also alone or in
      association with opioids for the treatment of moderate to severe pain. Acutely,
      NSAIDs may be more than mild analgesics, and may provide additional analgesia
      when combined with opioids. However, NSAIDs have ceiling effects and there is no
      therapeutic gain from increasing dosages beyond those recommended. As there is no
      clearly superior NSAID, the choice should be based on experience and the toxicity
      profile that probably relates to the COX-1:COX-2 ratio. Among the older drugs,
      ibuprofen seems to have these properties.Non-steroidal anti-inflammatory drugs
      have been shown to have an opioid-sparing effect. Although the value of a simple
      narcotic-sparing effect may be questioned in cancer pain treatment, the use of
      NSAIDs may be useful when the increase in opioid dosage determine the occurrence
      of opioid toxicity. Like opioids, NSAIDs should not be considered analgesics for
      a specific type or cause of pain. There is a lack of evidence for any difference
      between different routes of NSAIDs administration. The long-term toxicity of
      NSAIDs in cancer pain is poorly defined due to a lack of studies. A variety of
      strategies have been used in an attempt to reduce the risks associated with NSAID
      therapy. Those NSAIDs that are weak COX-1 inhibitors may be preferred. In
      addition, concomitant administration of misoprostol is recommended in patients at
      increased risk for upper gastrointestinal complications.

PMID- 11237781
TI  - The results of spinal cord stimulation in critical limb ischaemia: a review.
AB  - OBJECTIVES: to determine which patients with unreconstructible critical limb
      ischaemia (CLI) might benefit from spinal cord stimulation (SCS). METHODS:
      literature review. RESULTS: limb salvage in patients with an intermediate
      transcutaneous oxygen pressure (TcpO2) was not significantly higher with SCS
      (76%) than with conservative therapy (p=0.08). However, a limb salvage of 88% was
      achieved with SCS if the difference between the supine and sitting TcpO2 baseline
      values (DeltaTcpO2) was > or =15 mmHg. A rise in TcpO2 after trial stimulation of
      at least 15% resulted in a limb salvage of 77% at 18 months (p<0.01). CONCLUSION:
      randomised studies show no benefit of SCS over conservative therapy in patients
      with non-reconstructible CLI. However, data from experimental and non-randomised
      studies suggest this may be due to sub-optimal patient selection for SCS. Further
      trials are needed to identify subgroups who may benefit from SCS.

PMID- 11237782
TI  - Duplex ultrasound for assessment of superior mesenteric artery blood flow.
AB  - Duplex ultrasound (DU) is recognised as a valuable tool for the assessment of
      blood flow in many vascular territories. The application of this technique to the
      superior mesenteric artery (SMA) has increased rapidly throughout the last
      decade. The purpose of this review is to collate currently available information
      on the utility of SMA DU, both in terms of research and clinical practice.
      Research investigations have revealed low intra- and interobserver variability in
      the estimation of Doppler variables, while reliable evaluation of B-mode
      dimensions requires repeated measurements. SMA blood flow velocity has been found
      to be dependent upon changes in central haemodynamics and in peripheral
      resistance, which was documented in studies with hypotension, medication and post
      prandially. Food intake induces mesenteric vasorelaxation reflected by a 10-fold
      increase in the diastolic velocity. This feature has been utilised in studies on
      mesenteric physiology, which confirmed parasympathetic activity during
      hypovolaemia, and showed that exercise increases splanchnic resistance and
      reduces its blood flow following a 50% reduction in the hepato-splenic and a 25%
      reduction in the mesenteric blood flow. Clinical studies have documented high
      sensitivity and specificity of DU in detection of disease in splanchnic arteries.
      Diastolic velocity was found to be the most accurate indicator of SMA stenosis,
      while an absent Doppler signal from a well visualised vessel has been found to be
      a reliable predictor of occlusion. The high predictive value of DU in the
      detection of mesenteric artery disease, together with its simplicity and non
      invasiveness, suggests that DU should take precedence over arteriography in both
      clinical practice and laboratory investigations.

PMID- 11237783
TI  - Quality of life in patients with intermittent claudication using the World Health
      Organisation (WHO) questionnaire.
AB  - OBJECTIVE: to assess quality of life (QOL) in patients with intermittent
      claudication. DESIGN: a prospective, open study. MATERIAL AND METHOD: one hundred
      and fifty-one consecutive claudicants (100 men, 51 women), and 161 healthy
      controls (70 men and 91 women) completed an adapted version of the World Health
      Organisation Quality of Life Assessment Instrument-100. RESULTS: patients scored
      significantly worse on the domains Physical health and Level of independence, as
      well as on the facets Pain and discomfort, Energy and fatigue, Mobility,
      Activities of daily living, Dependence on medication and treatments, Working
      capacity, Negative feelings, Recreation and leisure and Overall QOL and general
      health. Increasing disease to incapacitating claudication affected only the facet
      Mobility and the domain Level of independence. CONCLUSION: QOL in patients with
      intermittent claudication is reduced in many aspects. Where co-morbidity seems to
      affect QOL strongly, the effect of walking distance on QOL might be small. These
      findings may justify a reserved attitude towards invasive, even minimally
      invasive treatment of these patients.

PMID- 11237784
TI  - Trends in provision of distal arterial reconstruction in Scotland 1989-1999.
AB  - OBJECTIVES: to establish if access to distal arterial reconstructive surgery is
      equally distributed within the health boards of Scotland and to establish if any
      variations in practice are reflected in lower limb amputation. METHODS: a
      retrospective, descriptive study using hospital discharge data (Scottish
      Morbidity Record-1) from 1989 to 1999. RESULTS: the rate of distal arterial
      reconstruction in Scotland increased from 0.9 per 100 000 population in 1989,
      peaked at 2.6 per 100 000 in 1994 and has since declined steadily to 1.6 per 100
      000 in 1999. There was up to 17-fold variation in annual rates of distal
      reconstruction between the 12 mainland health boards. The variations in distal
      reconstruction between the health boards were not reflected in variations in
      amputation rate nor is the decline in distal reconstruction easily explained by
      increased angioplasty. CONCLUSIONS: rates of distal arterial reconstruction in
      Scotland fall well below those in other European countries. It is likely that
      insufficient distal operations are undertaken to sufficiently impact on
      amputation rates. The study recommends an increased provision of specialist
      vascular surgical expertise in Scotland.

PMID- 11237785
TI  - Variability in measurement of internal carotid artery stenosis by arch
      angiography and duplex ultrasonography--time for a reappraisal?
AB  - OBJECTIVES: to determine the inter- and intra-observer variability of ICA
      stenosis measurement using duplex, ECST and NASCET methods. DESIGN: a
      retrospective review of arch angiograms and carotid duplex scans in 50 patients.
      MATERIALS AND METHODS: carotid stenoses were calculated by three independent
      observers according to NASCET and ECST methods. Variation between observers for
      NASCET and ECST was determined. For each observer, the variation between NASCET
      and ECST was determined. The variation between duplex and both NASCET and ECST
      was determined. RESULTS: inter-observer agreement on the degree of ICA stenosis
      was clinically and statistically good for NASCET but was poorer for ECST. For
      each observer, comparison between NASCET and ECST showed 95% limits of agreement
      of around 50 percentage points. Comparison of duplex with NASCET and ECST showed
      similar 95% limits of agreement. CONCLUSIONS: arch angiography allows
      reproducible measurement of carotid stenosis by the NASCET method between
      different observers. For the ECST method, reproducibility is not so good.
      Variations in results between NASCET and ECST and between angiography and duplex
      are significant. In view of the similar results of the NASCET and ECST trials,
      this suggests that degree of stenosis may only be a surrogate marker for outcome
      following carotid endarterectomy.

PMID- 11237786
TI  - Redo bypass surgery to the infrapopliteal arteries for critical leg ischaemia.
AB  - OBJECTIVES: to evaluate the results of redo bypass surgery to the infrapopliteal
      artery and the value of adjuvant arteriovenous fistula (AVF) in this setting.
      DESIGN: retrospective study. MATERIALS: fifty-one redo reconstructions to the
      infrapopliteal arteries were done for critical leg ischaemia in 45 patients who
      have had primary infrainguinal reconstructions to the popliteal artery in 20
      cases (39%), the crural arteries in 18 (35%), and the pedal arteries in 13 (25%).
      METHODS: a PTFE prosthesis was used in 21 cases (41%). A Miller cuff was used in
      16 prosthetic grafts. Adjuvant AVF was added to three autogenous vein and 12
      prosthetic grafts. RESULTS: at 2 years, the primary patency rate was 42%, the
      secondary patency was 43%, the limb salvage was 67%, the survival was 77%, and
      53% of patients were alive with salvaged leg. The primary patency rate with a
      vein graft was 44% at 1 year, with prosthesis plus AVF 67%, but with prosthesis
      without AVF only 19%. Secondary patency rates were similar. Prosthetic graft with
      AVF and those without AVF achieved a 1-year leg salvage rate of 100% and 51%,
      respectively (p =0.01). Patients with adjuvant AVF had a worse 2-year survival
      rate that those without AVF (31% vs 89%) (p =0.007; RR: 8.87, CI 95%: 1.62
      48.42). CONCLUSIONS: redo bypass surgery using autogenous vein graft may achieve
      satisfactory long-term results. The use of adjuvant AVF may improve patency of
      redo infrapopliteal prosthetic bypass grafts.

PMID- 11237787
TI  - The lack of cardiovascular risk factor management in patients with critical limb
      ischaemia.
AB  - AIM: to define the level of management of cardiovascular risk factors in patients
      treated for critical limb ischaemia in a vascular surgical setting. MATERIALS AND
      METHODS: retrospective review of all (n =147) patients operated on for critical
      lower extremity ischaemia in 1998. We included pre- and postoperative cardiac
      events. RESULTS: only eight (5%) (95% CI; 2-9) were on lipid lowering treatment
      and 58 (39%) (95% CI; 31-47) using acetylsalicylic acid. CONCLUSIONS: only a
      minority of patients operated on for CLI were receiving adequate cardiovascular
      risk factor modification.

PMID- 11237788
TI  - Coagulation, fibrinolysis and platelet P-selectin expression in peripheral
      vascular disease.
AB  - OBJECTIVES: to examine coagulation, fibrinolysis, and platelet activity in
      patients with peripheral vascular disease (PVD). DESIGN: fifty consecutive PVD
      patients and 50 healthy volunteers. (Prospective comparative study.) MATERIALS
      AND METHODS: P-selectin expression in non-fixed, whole blood was measured flow
      cytometrically on non-stimulated and ADP- and TRAP-6-stimulated samples. Plasma
      fibrinogen, von Willebrand factor (vWF), tissue plasminogen activator (tPA), and
      plasminogen activator inhibitor-1 were determined using standard techniques.
      Disease severity was stratified on the basis of the ankle-brachial pressure index
      (ABPI) and the angiographic data were assessed using the Bollinger score.
      RESULTS: coagulation and fibrinolysis parameters as well as the P-selectin
      expression on both stimulated and non-stimulated platelets were significantly
      increased in patients vs controls (all p<0.01). The respective sensitivity and
      specificity were as follows: P-selectin expression (81%, 94%), vWF (72%, 86%),
      fibrinogen (64%, 98%), PAI-1 (44%, 90%), tPA (15%, 100%). P-selectin expression
      on TRAP-6-stimulated MP correlated with disease severity (r=0.40, p<0.01).
      CONCLUSIONS: these findings support the concept of ongoing thrombogenesis in the
      subclinical progression of PVD and demonstrate the high diagnostic sensitivity of
      flow cytometric analysis of platelet activation.

PMID- 11237789
TI  - Can ultrasound replace arteriography in the management of chronic arterial
      occlusive disease of the lower limb?
AB  - OBJECTIVES: to investigate whether colour duplex scanning can be used as the sole
      diagnostic investigation prior to lower limb revascularisation. PATIENTS AND
      METHODS: the results of angiography and duplex were compared in 80 limbs (69
      claudication, 11 critical limb ischaemia [CLI]) from 68 patients. RESULTS:
      excellent diagnostic agreement (kappa value 0.89, 95% CI 0.85-0.93) was achieved
      at the femoropopliteal segment. Agreement was good for the aorto-iliac segment
      (kappa value 0.69, 95% CI 0.61-0.77) and moderate for the infrapopliteal segment
      (kappa value 0.59, 95% CI 0.55-0.63). Similarly, in the decision-making process
      excellent agreement was achieved for the femoropopliteal segment (kappa value
      0.91, 95% CI 0.88-0.94), good for the aortoiliac segment (kappa value 0.62, 95%
      CI 0.56-0.68), and moderate for the infrapopliteal segment (kappa value 0.46, 95%
      CI 0.42-0.50). Duplex detected patent 12 tibial arteries in 10 limbs that were
      not opacified on arteriography. In four limbs duplex revealed significant disease
      in the above knee popliteal artery that was missed on arteriography. CONCLUSIONS:
      treatment of femoropopliteal disease can be based upon duplex alone in the great
      majority of cases. However, where there is disease in the aortoiliac segment, or
      where infrapopliteal revascularisation is long considered both duplex and
      angiography should be performed to maximise pre-operative information.

PMID- 11237790
TI  - Interobserver variation of colour duplex scanning of the popliteal,tibial and
      pedal arteries.
AB  - OBJECTIVES: to determine interobserver variation in the measurement of Peak
      Systolic Velocity (PSV) and grading of disease by means of Duplex scanning (DS)
      in the popliteal, tibial and pedal arteries. DESIGN: prospective validation
      study. MATERIALS: twenty-four consecutive patients with severe claudication
      (n=6), ischaemic rest pain (n=11) and tissue loss (n=7). METHODS: two vascular
      technologists independently examined the popliteal, tibial and pedal arteries.
      The PSV was recorded in 15 arterial segments that were graded with B-mode and
      Doppler parameters as fully patent, severely diseased or occluded. Concordance in
      PSV recordings was expressed as intraclass correlation coefficients (ICC).
      Agreement in artery assessment was expressed as weighted kappa-values. RESULTS:
      the ICC for PSV measurements was 0.90 (95% CI, 0.86 to 0.93) within the popliteal
      and tibial arteries and 0.64 (95% CI, 0.37 to 0.81) within the pedal arteries.
      Agreement for grading disease was good within the popliteal and tibial arteries
      (kappa 0.66, 95% CI, 0.58 to 0.74), and moderate within the pedal arteries (kappa
      0.54, 95% CI 0.33 to 0.74). The presence of diabetes or stage of disease did not
      influence interobserver agreement. CONCLUSION: interobserver agreement of DS is
      good within the popliteal and tibial arteries and moderate within the pedal
      arteries.

PMID- 11237791
TI  - The incidence of small abdominal aortic aneurysms and the change in normal
      infrarenal aortic diameter: implications for screening.
AB  - AIM: to study the incidence of small abdominal aortic aneurysms (AAA), and to
      investigate what proportion of normal infrarenal aortic diameters (IAD) expand
      with age. METHODS: longitudinal follow-up in a population-based aneurysm
      screening programme. The infrarenal aortic diameter (IAD) was measured by
      ultrasound. A second scan was performed in subjects with a normal aorta after an
      average of 5.5 years. RESULTS: data were analysed from 4072 subjects, 464 with a
      small AAA and 3608 with a normal aorta. The infrarenal aorta expanded in 15% of
      subjects, but significant growth (>5 mm) occurred in only 7%. Age and initial
      diameter were independent predictors for aortic dilatation. The effect of
      diameter at first screen was non-linear. The relative risk for expansion
      increased dramatically for IADs over 2.5 cm (test for departure of trend:
      chi2=52, p<0.0001). The effect of age was also non-linear, the risk of expansion
      was highest in the 60-69 year old age group; test for departure of trend
      (chi2=13, p=0.002). The incidence of new aneurysms was 3.5 per 1000 person-years
      (py) (95% CI: 2.8-4.4). The highest incidence of new aneurysms was found in the
      60 to 69 year old age group. CONCLUSION: only a small proportion of the
      population is prone to aortic dilatation. Patients over 70 with an IAD <2.5 cm
      can be discharged from follow-up.

PMID- 11237792
TI  - Differences in renal response between endovascular and open repair of abdominal
      aortic aneurysms.
AB  - OBJECTIVES: to determine the difference in renal and systemic response between
      open and endovascular aneurysm repair. MATERIALS AND METHODS: we studied
      prospectively 22 patients undergoing open repair (OR) and 15 patients undergoing
      endovascular repair (ER). Blood and urine samples were taken preoperatively (T0)
      and before clamping of the aorta or femoral artery (T1) and 5 min (T2), 1 h (T3),
      6 h (T4), 24 h (Day 1) and 48 h (Day 2) after declamping. Albumin/creatinin ratio
      (AC ratio) in urine, serum albumin, serum creatinin, serum C-reactive protein and
      serum lactate were determined. RESULTS: the urinary AC ratio in ER was
      significantly lower than in OR (p<0.001). In both groups the rise in urine
      albumin/creatinin ratio after declamping (T2, T3) was significant (p<0.001). C
      reactive protein was raised significantly at day 1 and 2 in both groups (p<0.001)
      with no difference between the groups. Serum lactate values were significantly
      higher in OR. There was a significant increase in serum lactate 6 h after
      declamping in the ER group. CONCLUSIONS: after endovascular repair renal damage
      is less compared to open repair. There is a significant systemic reaction to the
      endovascular repair causing mild, short-lasting damage to the kidney. This
      systemic response is most probably induced by a combination of ischaemia
      reperfusion injury and the surgical trauma of the procedure. Other possible
      explanations are discussed.

PMID- 11237793
TI  - The relationship between abdominal aortic aneurysm distensibility and serum
      markers of elastin and collagen metabolism.
AB  - BACKGROUND: abdominal aortic aneurysm (AAA) distensibility may be an independent
      predictor of growth and rupture, possibly because it reflects changes in aortic
      wall structure and composition. AIM: to determine whether AAA distensibility is
      related to circulating markers of elastin and collagen metabolism. METHODS: sixty
      two male patients of median age (IQR) 68 (65-72) years with asymptomatic AAA of
      median (IQR) diameter 42 (37-45) mm were prospectively studied. Pressure-strain
      elastic modulus (Ep) and stiffness (beta) were measured using an ultrasonic echo
      tracker (Diamove). Serum elastin peptides (SEP), plasma elastin-alpha1
      antitrypsin complex (E-AT), procollagen III-N-terminal propeptide (PIIINP) were
      measured by enzyme-linked immunoassay. RESULTS: age and smoking adjusted Ep and
      beta were significantly inversely related to SEP (r=-0.33 and r=-0.31
      respectively, both p<0.02) and E-AT (r=-0.27 and r=-0.27 respectively, both
      p<0.05) both of which indicate elastolysis. By contrast, there was a significant
      positive correlation between PIIINP, indicative of increased collagen turn-over,
      and both Ep and beta (both r=0.45, p<0.01 unadjusted correlations). CONCLUSION:
      increased elastolysis is associated with increased AAA wall distensibility;
      whereas increased collagen turn-over is associated with reduced distensibility.

PMID- 11237794
TI  - To compare general, epidural and local anaesthesia for endovascular aneurysm
      repair (EVAR).
AB  - OBJECTIVES: to compare general, epidural and local anaesthesia for endovascular
      aneurysm repair (EVAR). METHODS: retrospective analysis of 91 consecutive
      patients (age 43 to 89 years) who underwent EVAR under local (LA, 63 patients),
      epidural (EDA, 8 patients) and general (GA, 20 patients) anaesthesia. RESULTS:
      EVAR was successfully achieved in all patients without mortality or neurological,
      cardiac and respiratory complications. Vasopressive support as well as median
      fluid balance were significantly lessened in the LA group compared to GA group
      (p<0.0002). Stay in the Intensive Care Unit was necessary in 17 (27%), four (50%)
      and 14 (70%) patients, respectively, and median hospital stay was 3, 4.5, and 5.5
      days, with a statistically significant difference between LA and GA group
      (p<0.0005). CONCLUSION: LA is a safe anaesthetic method for the endovascular
      repair of infrarenal abdominal aneurysm, offering several advantages: simplicity,
      stable haemodynamics, and reduced consumption of ICU and hospital beds.

PMID- 11237795
TI  - Inferior vena cava reconstruction using internal jugular vein.

PMID- 11237796
TI  - A new collateral pathway in a patient with renal artery occlusion.

PMID- 11237797
TI  - Secondary haemorrhage complicating methicillin-resistant Staphylococcus aureus
      infection in a popliteal to posterior tibial bypass graft. A role for free flaps?

PMID- 11237798
TI  - CD8+ cytotoxic lymphocyte responses against cytomegalovirus after liver
      transplantation: correlation with time from transplant to receipt of tacrolimus.
AB  - The effects of the immunocompromised state after liver transplantation on the
      frequency of cytomegalovirus-specific cytotoxic T lymphocytes (CTL) were
      investigated in 93 patients by using HLA class I tetrameric complexes
      corresponding to HLA-A*0201, HLA-B*0702, HLA-B*0801, and HLA-B*3501 refolded with
      peptides from the ppUL83 matrix protein. ppUL83 CTL frequencies were suppressed
      during the first 6 months after transplantation. Patients with >1 HLA-restricted
      response detected had high correlation among ppUL83 CD8(+) CTL frequencies
      restricted by different HLA haplotypes (Spearman's rho=.67; P<.0001). There was
      an inverse correlation among levels of the calcineurin inhibitor, tacrolimus, and
      ppUL83 CD8(+) CTL frequencies (r=-.31; P=.005), which is consistent with the
      presence of a large proportion (70%) of activated (CD38(+)) ppUL83 CD8(+) CTL
      within the population of HLA class I tetramer-positive cells.

PMID- 11237799
TI  - Daily or weekly therapy with resiquimod (R-848) reduces genital recurrences in
      herpes simplex virus-infected guinea pigs during and after treatment.
AB  - The effect of resiquimod (R-848), an immune-response modifier that is similar to
      imiquimod, on recurrent herpes simplex virus (HSV) was evaluated using the guinea
      pig model of genital herpes. Guinea pigs were intravaginally infected with HSV-2
      and then were randomized on day 14 to receive nothing or 0.1 mL/kg per dose of
      subcutaneous resiquimod, given either daily, every other day, or weekly from days
      15-35. During a 3-week course of therapy, recurrences in all 3 treated groups
      were reduced by >80%, compared with the control group. After therapy, recurrences
      remained significantly (P<.05) decreased in all 3 groups for the next 3 weeks.
      The group treated weekly developed the fewest recurrences. Significant increases
      in interleukin-2 levels, produced by incubation of mononuclear cells with HSV-2
      antigens, but not in circulating antibody also were detected in the treated
      groups. Resiquimod treatment may offer significant advantages to present
      antiviral therapies for the control of recurrent genital herpes.

PMID- 11237800
TI  - Altered cellular but not humoral reactions in children with complicated
      enterovirus 71 infections in Taiwan.
AB  - Enterovirus 71 (EV 71) infections have high neurovirulence and fatality. Immune
      responses were assessed in 78 patients with EV 71 infection. EV 71
      meningoencephalitis occurred more frequently in younger children and in boys. C
      reactive protein levels were not elevated, although total leukocyte counts were
      increased in these patients. The CD40-ligand expression on T cells significantly
      decreased in children with meningoencephalitis (P=.041). Polymorphism of the
      cytotoxic T lymphocyte antigen-4 (CTLA-4) at position 49 of exon 1 showed a
      higher frequency of G/G genotype in patients with EV 71 meningoencephalitis than
      in those without meningoencephalitis (18/31 vs. 14/47; P=.045) and in control
      subjects (18/31 vs. 25/93l; P=.007). Specific EV 71 neutralizing antibody titers
      were detectable but did not differ in children with and without
      meningoencephalitis in the acute and convalescent stages. Results from this study
      suggest that younger children with a certain CTLA-4 polymorphism and altered
      cellular but not humoral response may be linked to EV 71 meningoencephalitis.

PMID- 11237802
TI  - Cervical ectopy in adolescent girls with and without human immunodeficiency virus
      infection.
AB  - The objective of this study was to examine factors, including human
      immunodeficiency virus (HIV) infection, associated with ectopy among adolescent
      girls aged 12-20 years who were participating in an ongoing study of HIV
      infection in adolescents. Samples for detection of bacterial vaginosis, Chlamydia
      trachomatis, and Neisseria gonorrhoeae and a high-resolution photograph of the
      cervix for ectopy measurement were collected. Ectopy data for 189 and 92 HIV
      positive and -negative adolescents, respectively, were examined. Although
      univariate analysis found HIV infection and oral contraceptive use to be
      associated with the amount of ectopy, multivariate logistic regression analysis
      showed that only number of lifetime sex partners was a significant predictor,
      with more partners associated with less ectopy (odds ratio, 0.47; 95% confidence
      interval, 0.22-1.00; P=.05). In summary, adolescent girls with greater numbers of
      lifetime sex partners were more likely to have mature cervixes (less ectopy). HIV
      infection was not independently associated with ectopy.

PMID- 11237801
TI  - Human T cell leukemia virus Type I (HTLV-I) infection induces greater expansions
      of CD8 T lymphocytes in persons with HTLV-I-associated myelopathy/tropical
      spastic paraparesis than in asymptomatic carriers.
AB  - A quantitative study of the T cell receptor repertoire was performed ex vivo on
      CD4 and CD8 T cell subsets of human T cell leukemia virus type I (HTLV-I)
      infected asymptomatic carriers and patients with HTLV-I-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP). Indexes of oligoclonality that
      compiled all repertoire modifications were calculated for peripheral blood
      mononuclear cells and for CD4 and CD8 T cell subsets. Both patients with HAM/TSP
      and asymptomatic carriers had greater T lymphocyte expansions than did uninfected
      donors, which was independent of age and at least twice higher in the CD8 than in
      the CD4 cell compartment. Some expanded CD8 T cells corresponded to cytotoxic T
      lymphocytes directed against various epitopes of the immunodominant Tax protein.
      Patients with HAM/TSP had significantly higher CD8 cell expansions than did
      asymptomatic carriers. These results highlight the prognostic value of measuring
      CD8 T cell expansions during follow-up of HTLV-I infection.

PMID- 11237804
TI  - Antibiotic treatment in acute Otitis Media promotes superinfection with resistant
      Streptococcus pneumoniae carried before initiation of treatment.
AB  - Antibiotic-resistant pneumococci are difficult to eradicate from middle ear fluid
      (MEF) and the nasopharynx (NP). Bacteriologic eradication from the NP and MEF
      during acute otitis media (AOM) by 3 common antibiotic drugs was prospectively
      evaluated. In 19 (16%) of 119 MEF culture-positive patients, an organism
      susceptible to the treatment drug (Haemophilus influenzae, Streptococcus
      pneumoniae, or both) was isolated from the initial MEF, whereas resistant S.
      pneumoniae was present in the NP; in 9 (47%) patients, the initial resistant NP
      organism (identified by serotyping, resistance to the administered drug, and
      pulsed-field gel electrophoresis) replaced the susceptible MEF organism within
      only a few days after initiation of treatment. In regions where resistant
      pneumococci are prevalent, antibiotics may not only fail to eradicate the
      organisms, but they may often induce MEF superinfection with resistant
      pneumococci initially carried in the NP. This is an important mechanism by which,
      in recently treated patients, AOM infections often become refractory to
      treatment.

PMID- 11237803
TI  - Targeting to Fcgamma receptors, but not CR3 (CD11b/CD18), increases clearance of
      Bordetella pertussis.
AB  - In the absence of opsonizing antibodies, Bordetella pertussis, the causative
      agent of pertussis, readily binds to phagocytes via complement receptor 3 (CR3).
      After opsonization with antibodies, binding is mediated by IgG receptors
      (FcgammaR). The effect of targeting B. pertussis to either FcgammaR or CR3 was
      studied. The fate of unopsonized B. pertussis, IgG-opsonized B. pertussis, and B.
      pertussis opsonized with bispecific antibodies (BsAbs) directed to CR3 or
      FcgammaRII/-III was compared. IgG antibodies mediated binding and phagocytosis of
      B. pertussis via FcgammaR by polymorphonuclear leukocytes (PMNL) in vitro.
      Opsonization of B. pertussis with BsAbs directed against either CR3 or
      FcgammaRII/-III facilitated PMNL phagocytosis; however, in vivo studies with BsAb
      revealed that FcgammaR-mediated uptake facilitates B. pertussis clearance, in
      contrast to uptake via CR3. Targeting of B. pertussis to FcgammaRII/-III in mice
      deficient in FcgammaRII or FcgammaRIII indicated that the protective effect is
      attributable to FcgammaRIII. Competition between uptake via CR3 or FcgammaR may
      determine the outcome of natural infection.

PMID- 11237805
TI  - Pneumococcal carriage and otitis media induce salivary antibodies to pneumococcal
      surface adhesin a, pneumolysin, and pneumococcal surface protein a in children.
AB  - Local antibodies probably contribute to defense against Streptococcus pneumoniae.
      This study examined whether pneumococcal carriage and acute otitis media (AOM)
      induce mucosal antibodies to potential vaccine candidates pneumococcal surface
      adhesin A (PsaA), pneumolysin (Ply), and pneumococcal surface protein A (PspA).
      IgA to all 3 proteins was detected by EIA in saliva of 329 children at ages 6,
      12, 18, and 24 months and of 17 adults. A higher proportion of IgA-positive
      samples and higher antibody concentrations were seen in children with pneumococci
      positive cultures of nasopharyngeal samples or middle ear fluid than in children
      with all cultures negative for pneumococci. The strong correlation between IgA
      and the presence of the secretory component suggests that the IgA was secretory.
      The findings indicate that pneumococcal carriage and AOM induce local production
      of anti-PsaA, anti-Ply, and anti-PspA antibodies early in life.

PMID- 11237806
TI  - Phylogenetic and pathotypic similarities between Escherichia coli isolates from
      urinary tract infections in dogs and extraintestinal infections in humans.
AB  - Seventeen Escherichia coli isolates from dogs with urinary tract infection (UTI)
      were characterized with respect to phylogenetic background and virulence genotype
      and were compared with the E. coli reference (ECOR) collection and with human
      clinical isolates with similar serotypes from patients with diverse
      extraintestinal infections. Most of the canine urine isolates were from
      (virulence-associated) E. coli phylogenetic groups B2 or D, expressed papG allele
      III, and exhibited numerous other putative virulence genes that are
      characteristic of human extraintestinal pathogenic E. coli (ExPEC). Close
      phylogenetic and pathotypic correspondence was documented within 5 clonal groups
      among individual canine and human isolates, including archetypal human ExPEC
      strains CFT073 (O6:K2:H1), 536 (O6:K15:H31), and J96 (O4:K-:H5). These findings
      suggest that canine UTI isolates, rather than being dog-specific pathogens, as
      previously suspected, may pose an infectious threat to humans. Commonality
      between canine and human ExPEC has potentially important implications for disease
      prevention, antibiotic resistance avoidance, and studies of pathogenesis.

PMID- 11237807
TI  - Azithromycin prophylaxis during a hospital outbreak of Mycoplasma pneumoniae
      pneumonia.
AB  - Outbreaks of Mycoplasma pneumoniae (MP) in closed communities can have a high
      attack rate and can last several months. Azithromycin chemoprophylaxis has not
      been evaluated as a means of limiting transmission. This randomized, double
      blinded placebo-controlled trial of azithromycin was conducted among asymptomatic
      hospital employees during an MP outbreak. Oropharyngeal swabs were obtained for
      detection of MP by polymerase chain reaction, and questionnaires were
      administered to assess clinical illness. Of the 147 employees who were enrolled,
      73 received azithromycin and 74 received placebo. Carriage was similar within and
      between groups at weeks 1 and 6 (9.6% vs. 6.7% and 10.3% vs. 13.2%,
      respectively). Four episodes of clinically significant respiratory illness
      occurred in the azithromycin group versus 16 episodes in the placebo group
      (protective efficacy, 75%; 95% confidence interval, 28%-91%). Use of azithromycin
      prophylaxis in asymptomatic persons during an MP outbreak in a closed setting may
      be of value in reducing clinical illness.

PMID- 11237808
TI  - Effects of vaginal intercourse with and without a condom on vaginal flora and
      vaginal epithelium.
AB  - Effects of a single episode of intercourse on vaginal flora and epithelium were
      examined in subjects randomly assigned to groups that used no condom or
      lubricated nonspermicide condoms. Subjects were evaluated at visits before (1
      month and 1-2 days) and after (8-12 h, 2-3 days, and 6-8 days) an index episode
      of sexual intercourse. The 22 subjects who used no condoms had significantly more
      Escherichia coli and a high concentration (> or =10(5) cfu/mL) of E. coli in the
      vagina (both, P<.001) and urine (all <10(5) cfu/mL; P=.004) at visit 3 than at
      visits 1 and 2. The 20 subjects who used condoms had a trend toward more vaginal
      E. coli (P=.06) and a significant increase in other enteric gram-negative rods
      (P=.001) after intercourse. Intercourse was not associated with gross,
      colposcopic, or histologic vaginal epithelial abnormalities.

PMID- 11237809
TI  - Pseudomonas aeruginosa infection of respiratory epithelium in a cystic fibrosis
      xenograft model.
AB  - Pulmonary infection with Pseudomonas aeruginosa in patients with cystic fibrosis
      (CF) causes a chronic destructive bronchitis. A xenograft model was used to study
      the susceptibility of the CF respiratory epithelium to P. aeruginosa strain PAK
      and the virulence of certain mutants. Despite an early trend toward increased
      susceptibility, colonization of CF xenografts (ID(95), 62 colony-forming units
      [cfu]) was not statistically different (P=.5) than in xenografts with normal
      respiratory cells (ID(95), 1.2x10(3) cfu). Infection severity in 12 CF xenografts
      (mean polymorphonuclear leukocyte [PMNL] density, 1.88x10(6)+/
      1.75x10(6)/xenograft) was similar to that in 16 non-CF xenografts (3.19x10(6)+/
      2.45x10(6) PMNL/xenograft; P=.38), despite slightly greater bacterial density in
      the CF xenografts (mean, 1.57+/-2.73x10(6) cfu/xenograft) versus xenografts with
      normal epithelium (mean, 1.03+/-1.3x10(6) cfu/xenograft). P. aeruginosa mutants
      pilA and fliF, but not rpoN, colonized normal respiratory xenografts, indicating
      that colonization and infection in this model depend on an uncharacterized RpoN
      controlled gene. This model appears to be suitable for genetic study of P.
      aeruginosa virulence but not of the CF respiratory tract's unique susceptibility.

PMID- 11237810
TI  - HLA-B*35-restricted CD8 T cell epitopes in the antigen 85 complex of
      Mycobacterium tuberculosis.
AB  - Few target epitopes have been described for human CD8 T lymphocytes in antigens
      of Mycobacterium tuberculosis. By use of a reverse immunogenetics approach, 23
      motif-bearing peptides of the Ag85 complex were tested for binding to HLA-B*35,
      one of the common B-types in West Africa. Three 9-mer peptides bound with high
      affinity to HLA-B*3501 and displayed low dissociation rates of peptide-major
      histocompatibility complexes (MHCs). IC(50) and half-life values of peptide-MHC
      class I complexes were in the same range as reported earlier for other
      immunogenic peptides. Immune responses against peptide Ag85C (aa 204-212)
      WPTLIGLAM were characterized in detail. Peptide-stimulated effector cells were
      able to kill macrophages infected with M. tuberculosis or bacille Calmette
      Guerin. Peptide-specific CD8 T cells could be visualized by using HLA-B*3501
      tetramers and were shown to produce interferon-gamma and tumor necrosis factor
      alpha. Together with other published epitopes, these peptides can be used to
      study more closely the role of CD8 T cells in mycobacterial infection and
      tuberculosis.

PMID- 11237811
TI  - Chloroquine antagonizes the proinflammatory cytokine response to opportunistic
      fungi by alkalizing the fungal phagolysosome.
AB  - Recent observations demonstrated that the antimalarial drug chloroquine (CQ) can
      kill the opportunistic fungus Cryptococcus neoformans. Since CQ blunts
      lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha release, it
      was hypothesized that this drug would also interfere with the inflammatory
      response to C. neoformans and Candida albicans, another fungal opportunist. CQ
      inhibited TNF-alpha release from peripheral blood mononuclear cells from healthy
      and human immunodeficiency virus-positive donors without affecting NF-kappaB
      activation. CQ reduced TNF-alpha mRNA levels by a pH-dependent mechanism in a
      manner similar to 2 unrelated alkalizing drugs (ammonium chloride and
      bafilomycin), which also inhibited TNF-alpha gene expression. Although CQ
      inhibited release of interleukin (IL)-1beta and IL-6, it did not affect IL-10 or
      macrophage inflammatory protein-1alpha production. Thus, CQ interferes with
      fungus-induced TNF-alpha expression by a mechanism that probably depends on the
      alkalization of endolysosomes. This contrasts with CQ's reported pH-independent
      inhibition of LPS-stimulated TNF-alpha release and suggests that the mechanism of
      CQ's anti-inflammatory effects is stimulus specific.

PMID- 11237812
TI  - Immunosuppressed surfactant protein A-deficient mice have increased
      susceptibility to Pneumocystis carinii infection.
AB  - Immunosuppressed Swiss Black mice deficient in surfactant protein A (SP-A(-/-))
      and wild-type control mice (SP-A(+/+)) were exposed to Pneumocystis carinii by
      environmental exposure, intratracheal inoculation, and direct exposure to other
      infected animals. The frequency and intensity of P. carinii infection were
      significantly greater in the SP-A(-/-) mice by all 3 methods of exposure. P.
      carinii free of SP-A and alveolar macrophages were isolated from SP-A(-/-) mice
      and were tested in an in vitro attachment assay. Pretreatment of P. carinii with
      human SP-A resulted in a significant dose-dependent increase of the adherence of
      P. carinii to the macrophages. Thus, SP-A plays a role in host defense against P.
      carinii in vivo, perhaps by functioning as a nonimmune opsonin.

PMID- 11237813
TI  - Interleukin (IL)-13 is the predominant Th2 cytokine in localized cutaneous
      leishmaniasis lesions and renders specific CD4+ T cells unresponsive to IL-12.
AB  - Semiquantitative reverse transcription-polymerase chain reaction analysis of
      leishmania lesion cytokine profile showed a Th2 cytokine expression pattern, as
      reflected by interleukin (IL)-4 and IL-13 mRNA expression. There was a
      predominance of IL-13 in most lesions from patients with American localized
      cutaneous leishmaniasis caused by Leishmania guyanensis. IL-13 production by
      peripheral blood mononuclear cells in response to specific leishmania antigens
      was confirmed in these patients. The absence of the second chain of the IL-12
      receptor (IL-12Rbeta2) mRNA expression in lesions and the presence of specific
      IgE and IgG4 in some serum samples demonstrated the functional role of these Th2
      cytokines. IL-13, unlike IL-4, rendered specific T cells unresponsive to IL-12 by
      inhibiting the expression of the IL-12Rbeta2 chain. These data establish the
      crucial role of IL-13 in human cutaneous leishmaniasis.

PMID- 11237814
TI  - Prevalence and familial aggregation of schistosomal liver morbidity in Kenya:
      evaluation by new ultrasound criteria.
AB  - Severe periportal fibrosis is not an inevitable consequence of infection with
      Schistosoma mansoni. Genetic predisposition may be a deciding factor in the
      development of disease. To assess the contribution of genetic factors in the
      severity of hepatic fibrosis, the degree of familial aggregation was determined
      in a Kenyan population. Schistosomal fibrosis was identified with hepatic
      ultrasound and newly proposed World Health Organization criteria, which include
      both qualitative and quantitative observations. These 2 aspects of the criteria
      correlated well with one another. The peak prevalence of ultrasound proven
      fibrosis trailed 5-10 years behind peak prevalence of infection and declined
      sharply after age 50 years. This pattern was consistent with either resolution of
      severe fibrosis over 10-20 years or early death of those severely affected.
      Genetic predisposition appears to be a weak factor in the development of severe
      disease in this population, since no household or familial aggregation could be
      identified.

PMID- 11237815
TI  - Malaria enhances expression of CC chemokine receptor 5 on placental macrophages.
AB  - Malaria and human immunodeficiency virus (HIV) coinfections are common in
      pregnant women in sub-Saharan Africa. The current study shows that placentas of
      malaria-infected women contain 3 times as much CC chemokine receptor 5 (CCR5) RNA
      as placentas of women without malaria. By immunohistochemistry, CCR5(+) maternal
      macrophages were seen in placentas from malaria-infected women but not in
      placentas from malaria-uninfected women. In addition, CCR5 also was found on
      fetal Hofbauer cells in placentas from both groups. Thus, malaria infections
      increase the potential reservoir for HIV in the placenta by increasing the number
      of HIV target cells.

PMID- 11237816
TI  - Multicenter evaluation of hepatitis C RNA levels among female injection drug
      users.
AB  - The purpose of this investigation was to identify factors that determine the
      blood level of hepatitis C virus (HCV) RNA. By use of a quantitative polymerase
      chain reaction assay, the level of HCV RNA was ascertained in stored serum
      samples from 676 women enrolled in a multicenter prospective investigation who
      were seropositive for anti-HCV antibodies. HCV RNA levels ranged from
      undetectable to 22.4x106 copies/mL in these women. Among the 520 women with
      detectable HCV RNA, levels were higher among those who were >41 years old and
      those who had human immunodeficiency virus (HIV) infection. After adjusting for
      age in a multivariate linear regression model, HCV RNA levels were more strongly
      associated with HIV RNA levels than with CD4(+) lymphocyte counts. However, <6%
      of person-to-person variance was explained by the factors evaluated. Additional
      research is needed to ascertain what determines the level of HCV RNA in blood.

PMID- 11237817
TI  - Human immunodeficiency virus-specific and CD3-redirected cytotoxic T lymphocyte
      activity in the human female reproductive tract: lack of correlation between
      mucosa and peripheral blood.
AB  - CD8(+) T cell phenotype and function were assessed in the female reproductive
      tracts (FRTs) of 3 human immunodeficiency virus (HIV)-positive patients who had
      undergone hysterectomy. FRT cytotoxic T lymphocyte (CTL) lytic activity from 1
      patient (patient 872) was detected by using CD3-dependent redirected-lysis assay
      and HIV-specific assay, concomitant with the presence of CD8(+) cells. In
      contrast, samples from the 2 other HIV-positive patients (patients 1356 and
      1364), who also were asymptomatic for HIV-associated illnesses, demonstrated no
      CTL activity in any solid tissue tested by either assay, despite activity by
      autologous peripheral blood mononuclear cells (PBMC). This absence of CTL
      activity was correlated with a relative absence of CD8(+) cells in the FRT,
      whereas CD8(+) cells were present in PBMC. Thus, CTL activity in PBMC may fail to
      correlate with mucosal activity. The finding of CTL activity in the FRT of
      patient 872 represents the first description of CTL in upper and lower FRT
      tissues of an HIV-positive woman.

PMID- 11237818
TI  - An outbreak of Salmonella serotype Thompson associated with fresh cilantro.
AB  - An outbreak of Salmonella serotype Thompson in California was identified through
      laboratory-based surveillance and investigated with case-control, traceback, and
      laboratory studies. There were 35 "sporadic" cases and a restaurant-associated
      outbreak of 41 cases with onset between 6 March and 31 March 1999. Three case
      patients were hospitalized. A case-control study found a significant association
      between illness and eating cilantro at a restaurant (63% of case patients vs. 34%
      of control subjects; odds ratio, 3.5; 95% confidence interval, 1.1-11.4).
      Although common distributors of cilantro were identified, inadequate records
      prohibited the identification of a single farm supplying cilantro. At room
      temperature, Salmonella Thompson grew more rapidly and to a higher concentration
      on chopped cilantro, compared with whole-leaf cilantro. Freshly made salsa (pH
      3.4) supported growth of Salmonella Thompson. Cilantro should be served promptly
      after chopping. Accurate records of the distribution of produce should be
      available, and bacterial contamination of produce should be prevented in retail
      and wholesale establishments, in packing sheds, and on farms.

PMID- 11237819
TI  - Human macrophage tumor necrosis factor (TNF)-alpha production induced by
      Trypanosoma brucei gambiense and the role of TNF-alpha in parasite control.
AB  - Trypanosoma brucei gambiense, a causative agent of sleeping sickness, induced a
      dose-dependent production of tumor necrosis factor (TNF)-alpha by human
      macrophages in vitro. TNF-alpha was also induced in the Mono Mac 6 cell line,
      which indicates a direct effect of parasite components on macrophages. Parasite
      soluble factors were also potent inducers of TNF-alpha. The addition of anti-TNF
      alpha to cocultures of macrophages and parasites increased the number of
      trypanosomes and their life span, whereas irrelevant antibodies had no effect.
      TNF-alpha may have a direct role (i.e., direct trypanolytic activity) and/or an
      indirect one, such as TNF-alpha-mediated induction of cytotoxic molecules. A
      direct dose-dependent lytic effect of TNF-alpha on purified parasites was
      observed. This lytic effect was inhibited by anti-TNF-alpha. These data suggest
      that, as in experimental trypanosomiasis, TNF-alpha is involved in parasite
      growth control in human African trypanosomiasis.

PMID- 11237820
TI  - Reliability of Cmin: inhibitory concentration ratios.

PMID- 11237822
TI  - Response of C-reactive protein and serum amyloid A to influenza A infection in
      older adults.
AB  - Influenza epidemics are associated with significant morbidity and mortality in
      the elderly, with a substantial proportion of deaths due to cardiovascular
      events. Elevations of acute-phase proteins have been associated with an increased
      risk of atherosclerotic events. Therefore, serum amyloid A (SAA) and C-reactive
      protein (CRP) were measured during influenza illness and 4 weeks later in 7 young
      persons, 15 elderly outpatients, and 36 hospitalized adults. Striking elevations
      were seen in mean acute SAA and CRP levels in all groups, but hospitalized
      patients had the highest levels (SAA, 503 vs. 310 microg/mL [P=.006]; CRP, 120
      vs. 34 microg/mL [P<.001]). The presence of dyspnea, wheezing, and fever was also
      associated with high CRP levels. Influenza infection is associated with
      significant elevations of SAA and CRP levels in elderly patients, especially
      those who require hospitalization. It is possible that direct effects of CRP may
      exacerbate preexisting atherosclerotic lesions and may help explain
      cardiovascular events associated with acute influenza.

PMID- 11237823
TI  - Influenza virus-stimulated generation of anti-human immunodeficiency virus (HIV)
      activity after influenza vaccination in HIV-infected individuals and healthy
      control subjects.
AB  - Influenza virus stimulation of leukocytes induces factors that suppress human
      immunodeficiency virus (HIV). The effect of influenza vaccination on influenza
      induced anti-HIV activity was investigated. Influenza vaccine was administered to
      25 control subjects and 20 HIV-infected patients. Antiviral activity, cytokine
      production, and influenza antibodies were assessed before and 2 and 6 weeks after
      vaccination. Immunization induced a statistically significant increase in
      antiviral activity in control subjects but not in HIV patients, although the
      number of patients who generated this activity increased. Pre- and
      postvaccination levels of anti-HIV activity were significantly lower in HIV
      patients. Vaccination of control subjects and HIV patients induced increases in
      production of interleukin-2 and interferon (IFN)-gamma, but not of IFN-alpha.
      Virus load and CD4 cell counts were not significantly altered. This study
      demonstrates impairment of antiviral activity in HIV patients, in addition to
      deficiencies in antibody responses and cytokine production. In summary, influenza
      vaccination can induce an increase in multiple immunologic components that
      remained impaired in HIV patients.

PMID- 11237824
TI  - Discordant increases in CD4+ T cells in human immunodeficiency virus-infected
      patients experiencing virologic treatment failure: role of changes in thymic
      output and T cell death.
AB  - Some patients infected with human immunodeficiency virus (HIV) who are
      experiencing antiretroviral treatment failure have persistent improvement in CD4+
      T cell counts despite high plasma viremia. To explore the mechanisms responsible
      for this phenomenon, 2 parameters influencing the dynamics of CD4+ T cells were
      evaluated: death of mature CD4+ T cells and replenishment of the CD4+ T cell pool
      by the thymus. The improvement in CD4+ T cells observed in patients with
      treatment failure was not correlated with spontaneous, Fas ligand-induced, or
      activation-induced T cell death. In contrast, a significant correlation between
      the improvement in CD4+ T cell counts and thymic output, as assessed by
      measurement of T cell receptor excision circles, was observed. These observations
      suggest that increased thymic output contributes to the dissociation between CD4+
      T cell counts and viremia in patients failing antiretroviral therapy and support
      a model in which drug-resistant HIV strains may have reduced replication rates
      and pathogenicity in the thymus.

PMID- 11237825
TI  - The effect of treatment of vaginal infections on shedding of human
      immunodeficiency virus type 1.
AB  - To assess the effect of treatment of vaginal infections on vaginal shedding of
      cell-free human immunodeficiency virus type 1 (HIV-1) and HIV-1-infected cells,
      HIV-1-seropositive women were examined before and after treatment of Candida
      vulvovaginitis, Trichomonas vaginitis, and bacterial vaginosis. For Candida
      (n=98), vaginal HIV-1 RNA decreased from 3.36 to 2.86 log(10) copies/swab
      (P<.001), as did the prevalence of HIV-1 DNA (36% to 17%; odds ratio [OR], 2.8;
      95% confidence interval [CI], 1.3-6.5). For Trichomonas vaginitis (n=55), HIV-1
      RNA decreased from 3.67 to 3.05 log(10) copies/swab (P<.001), but the prevalence
      of HIV-1 DNA remained unchanged (22%-25%; OR, 0.8; 95% CI, 0.3-2.2). For
      bacterial vaginosis (n=73), neither the shedding of HIV-1 RNA (from 3.11 to 2.90
      log(10) copies/swab; P=.14) nor the prevalence of DNA (from 21% to 23%; OR, 0.8;
      95% CI, 0.3-2.0) changed. Vaginal HIV-1 decreased 3.2- and 4.2-fold after
      treating Candida and Trichomonas, respectively. These data suggest that HIV-1
      transmission intervention strategies that incorporate diagnosis and treatment of
      these prevalent infections warrant evaluation.

PMID- 11237826
TI  - Pig-tailed macaques infected with human immunodeficiency virus (HIV) type 2GB122
      or simian/HIV89.6p express virus in semen during primary infection: new model for
      genital tract shedding and transmission.
AB  - Characterizing human immunodeficiency virus (HIV) expression in semen during
      primary infection remains essential to understanding the risk of sexual
      transmission. This investigation represents the first systematic evaluation of
      male genital tract shedding to use a nonhuman primate model, including the impact
      of exposure route and viral virulence. Male macaques were inoculated with either
      a chronic disease-causing virus (HIV-2(GB122); n=4 intravenous; n=4 intrarectal)
      or an acutely pathogenic simian/HIV strain (SHIV(89.6P); n=2 intravenous). All
      macaques were systemically infected, and seminal plasma virion-associated RNA
      (vRNA) levels were approximately 10-fold lower than those in blood. In HIV
      2(GB122) infection, seminal virus was delayed by 1-2 weeks compared with that in
      blood. Intrarectal inoculation resulted in a shorter duration of seminal vRNA
      expression and intermittent seminal cell provirus. No delays, higher peaks (
      approximately 50-fold), or longer durations in seminal virus expression were
      noted for SHIV(89.6P) infection. This novel model definitively establishes that
      virus dissemination results in early peak seminal levels and provides a basis for
      evaluating interventions targeting male genital tract expression.

PMID- 11237827
TI  - Sequential change of virus markers in seroconverters with community-acquired
      infection of human T lymphotropic virus type I.
AB  - Twenty-three human T lymphotropic virus type I (HTLV-I) seroconverters were
      identified among 1120 HTLV-I-seronegative adults followed up for 11 years in an
      area of Japan endemic for HTLV-I. The geometric mean titer of anti-HTLV-I was
      1:453 in the first year after seroconversion; the titer of each subject did not
      change significantly during 2-10 years of follow-up. HTLV-I proviral DNA load was
      quantified in 15 seroconverters, and a broad range of levels was observed-from
      <10 to >1000 copies/10(5) peripheral blood mononuclear cells. However, there was
      no obvious change in HTLV-I proviral DNA load over several years within
      individual subjects. Therefore, both proviral DNA load and humoral response in
      adult HTLV-I seroconverters were shown to stabilize within a few years after
      initial infection. In addition, 1 subject tested positive for HTLV-I proviral DNA
      before antibody seroconversion, which suggests the existence of a window period
      in community-acquired infection.

PMID- 11237828
TI  - Characterization of the importance of Staphylococcus epidermidis autolysin and
      polysaccharide intercellular adhesin in the pathogenesis of intravascular
      catheter-associated infection in a rat model.
AB  - A rat central venous catheter (CVC) infection model was used to assess the
      importance of the proteinacious autolysin (AtlE) and the polysaccharide
      intercellular adhesin (PIA) in the pathogenesis of Staphylococcus epidermidis CVC
      associated infection. Wild-type (wt) S. epidermidis O-47 was significantly more
      likely to cause a CVC infection than was either of the isogenic mutant strains
      (AtlE-negative [O-47mut1] or PIA-negative [O-47mut2]). Bacteria were retrieved
      from the explanted catheters of 87.5% of rats inoculated with S. epidermidis O
      47, compared with 25% of rats challenged with either S. epidermidis O-47mut1 or O
      47mut2 (P=.007). Peripheral bacteremia was documented in 75% of rats challenged
      with S. epidermidis O-47, compared with 12.5% and 25% challenged with O-47mut1
      and O-47mut2, respectively (P=.009). Metastatic disease was more common in rats
      inoculated with wt S. epidermidis, compared with AtlE- or PIA-deficient mutants.
      These results confirm the importance of initial adherence, associated with AtlE,
      and biofilm production, mediated by PIA, in the pathogenesis of S. epidermidis
      experimental CVC infection.

PMID- 11237829
TI  - Spontaneous mutations in the CsrRS two-component regulatory system of
      Streptococcus pyogenes result in enhanced virulence in a murine model of skin and
      soft tissue infection.
AB  - CsrS/CsrR is a 2-component system in Streptococcus pyogenes that negatively
      regulates hyaluronic capsule and several exotoxins. To detect spontaneous
      mutations in csrRS, mucoid and large colony variants of M1 strain MGAS166 were
      isolated from experimental murine skin infections. By use of complementation with
      a csrRS(+) plasmid, relevant mutations were also detected in 7 of 12 human
      clinical isolates. The presence of spontaneous mutants in mouse infection was
      associated with larger, more necrotic lesions. Most spontaneous changes in CsrR
      resulted from single amino acid substitutions, whereas most csrS mutations were
      frameshift or nonsense mutations. In 2 instances, IS1548 insertions were found in
      csrS. Experimental inoculation of mixtures of wild-type (wt) and csrRS(-)
      bacteria yielded larger, more necrotic lesions than did either strain at twice
      the inoculum, which suggests that these variants may exhibit pathogenic synergy.
      Spontaneous emergence of csrRS(-) mutants in vivo enhances the virulence of wt
      bacteria and increases severity of murine skin infection.

PMID- 11237830
TI  - Helicobacter pylori neutrophil-activating protein stimulates tissue factor and
      plasminogen activator inhibitor-2 production by human blood mononuclear cells.
AB  - Helicobacter pylori neutrophil-activating protein (HP-NAP) is a virulence factor
      that activates phagocytic NADPH-oxidase. The effect of HP-NAP on the production
      of tissue factor (TF), plasminogen activator inhibitor-2 (PAI-2), and urokinase
      type plasminogen activator (u-PA) by human blood mononuclear cells (MNC) was
      evaluated by using functional and immunological assays and mRNA analysis. HP-NAP
      induced time- and dose-dependent increases in TF and PAI-2, with a maximal effect
      at 300 nmol/L (>15-fold increase in antigens). No changes in u-PA were observed.
      When whole bacteria were used, an H. pylori mutant lacking HP-NAP was
      significantly less active than the wild-type strain. MNC from a patient with
      chronic granulomatous disease behaved as do normal cells, which indicates that HP
      NAP effects can occur independently of NADPH-oxidase. HP-NAP, by inducing the
      coordinate expression of cell procoagulant and antifibrinolytic activities, might
      favor fibrin deposition and contribute to the inflammatory reaction of gastric
      mucosa elicited by H. pylori.

PMID- 11237831
TI  - The United States National Prospective Hemolytic Uremic Syndrome Study:
      microbiologic, serologic, clinical, and epidemiologic findings.
AB  - The frequency of Shiga toxin-producing Escherichia coli (STEC) serotypes
      associated with postdiarrheal hemolytic uremic syndrome (HUS) cases among
      children and adults in the United States and the proportion with IgM or IgG
      lipopolysaccharide antibodies to E. coli O157 were determined by use of a
      nationwide sample from January 1987 through December 1991. Among 83 patients,
      STEC were isolated from 30 (43%) of 70 whose stool cultures yielded bacterial
      growth (25 E. coli O157 isolates and 5 non-O157 STEC isolates). Fifty-three (80%)
      of 66 patients with serum samples had positive O157 lipopolysaccharide antibody
      titers. Of the 83 patients, 60 (72%) had evidence of STEC infection, including 6
      of 8 adults whose illnesses also met criteria for thrombotic thrombocytopenic
      purpura. Data from a subset of patients suggest that E. coli O157 was the cause
      of > or = 80% of the STEC infections. All 3 women who were postpartum had
      evidence of E. coli O157 infection. STEC infection should be considered the
      likely cause for all persons with postdiarrheal HUS.

PMID- 11237832
TI  - Further characterization of Escherichia coli brain microvascular endothelial cell
      invasion gene ibeA by deletion, complementation, and protein expression.
AB  - The ibeA gene (ibe10) previously identified by TnphoA mutagenesis is part of a 50
      kDa full-length open-reading frame (ORF) encoded by a 1.37-kb DNA fragment. An
      isogenic in-frame deletion mutant of ibeA (ZD1) was constructed by chromosomal
      gene replacement with a suicide plasmid pCVD442 carrying a 2.1-kb DNA fragment
      with an ibeA deletion. Similar to the previously described TnphoA insertion
      mutant of ibeA, the isogenic ibeA deletion mutant ZD1 was significantly less
      invasive in human brain microvascular endothelial cells (BMECs) than the parent
      strain. The mutant ZD1 was fully complemented by the ibeA ORF. The ibeA gene was
      subcloned into pET28a(+) and was expressed as a recombinant protein with an N
      terminal histidine tag. The recombinant IbeA protein had much greater activity
      (50 times) in blocking the invasion of BMECs by Escherichia coli K1 than did the
      partial protein fragment, which provides further evidence that ibeA is an
      important determinant for E. coli K1 invasion of BMECs.

PMID- 11237833
TI  - Active immunization with a detoxified Escherichia coli J5 lipopolysaccharide
      group B meningococcal outer membrane protein complex vaccine protects animals
      from experimental sepsis.
AB  - The passive infusion of antibodies elicited in rabbits with a detoxified J5
      lipopolysaccharide (LPS)/group B meningococcal outer membrane protein complex
      vaccine protected neutropenic rats from heterologous lethal gram-negative
      bacterial infection. In this study, active immunization was studied in
      neutropenic rats infected with Pseudomonas aeruginosa, in the presence or absence
      of ceftazidime therapy, and with Klebsiella pneumoniae. This vaccine elicited a >
      200-fold increase in anti-J5 LPS antibody, which remained elevated throughout the
      duration of cyclophosphamide-induced neutropenia and for < or = 3 months. There
      was improved survival among immunized versus control animals: 48% (13/28) versus
      7% (2/29) in Pseudomonas-challenged rats; 61% (11/18) versus 0% (0/10) in
      Pseudomonas- and ceftazidime-treated rats; and 64% (9/14) versus 13% (2/15) in
      Klebsiella-challenged rats (P < 0.01 for each comparison). Immunized animals had
      lower levels of bacteria in organs and lower levels of circulating endotoxin at
      the onset of fever. In conclusion, active immunization with an anti-endotoxin
      vaccine improved survival after infection with > or = 2 heterologous, clinically
      relevant bacterial species in immunocompromised animals. Active immunization with
      this vaccine merits further investigation.

PMID- 11237834
TI  - Knock-knock: a population-based survey of risk behavior, health care access, and
      Chlamydia trachomatis infection among low-income women in the San Francisco Bay
      area.
AB  - To estimate the prevalence of urogenital chlamydial infection among young, low
      income women in northern California and to describe correlates of infection, a
      population-based door-to-door household cluster survey was conducted from 1996
      through 1998. The participants included 1439 women 18-29 years of age, with a
      mean age of 24 years, most of whom were African American (43%) or Latina (23%)
      and had a median income of $500-$999 per month. Most (94%) had received health
      care in the past year, and approximately 50% was covered by state insurance
      programs. Although more than half (62%) had had a recent pelvic examination, only
      42% had recently used a condom with a new partner. The prevalence of urogenital
      chlamydial infection was 3.2% (95% confidence interval, 2.2%-4.2%). Women with
      chlamydia were more likely to be younger (18-21 years of age) and nonwhite and to
      have lower socioeconomic status. These data demonstrated an approximately 2-3
      fold greater burden of infection than routine surveillance data have suggested.

PMID- 11237835
TI  - Glyphosate inhibits melanization of Cryptococcus neoformans and prolongs survival
      of mice after systemic infection.
AB  - Cryptococcus neoformans is a major fungal pathogen and is a relatively common
      cause of life-threatening meningoencephalitis. Glyphosate is a widely used
      herbicide that inhibits the synthesis of aromatic amino acids via the shikimate
      acid pathway. This study investigated the effects of glyphosate on C. neoformans
      growth, melanization, and murine infection. C. neoformans was relatively
      resistant to glyphosate, requiring concentrations >250 microg/mL for inhibition.
      Melanization of C. neoformans in the presence of L-dopa was inhibited by
      subinhibitory concentrations of glyphosate. Glyphosate inhibited
      autopolymerization of L-dopa and oxidation of L-epinephrine by cryptococcal
      cells, which is mediated by a laccase. Administration of glyphosate to mice
      infected with C. neoformans delayed melanization of yeast cells in vivo and
      prolonged average mouse survival. The results suggest that inhibition of
      melanization in vivo may facilitate control of C. neoformans infection.

PMID- 11237836
TI  - Placental malaria is associated with cell-mediated inflammatory responses with
      selective absence of natural killer cells.
AB  - Immunosuppression, particularly of cell-mediated responses, has classically been
      thought to play a major role in the increased susceptibility to malaria observed
      in pregnant women. An immunohistochemical characterization of the inflammatory
      infiltrate in a group of 41 placentas from women living in a Plasmodium
      falciparum-hyperendemic area in Tanzania revealed a marked increase in the number
      of monocytes and macrophages and cytotoxic T cells in the intervillous space of
      placentas with active malaria infection, compared with noninfected placentas,
      placentas from women with past infection, and a control group of placentas from
      Spain. This increase was associated with the severity of the infection. High
      numbers of monocytes and macrophages were associated with low birth weight. We
      also detected a complete absence of NK cells in the intervillous space in all
      placentas. This apparently physiological absence of NK cells may contribute to
      hindering the clearance of the parasite. These results indicate that placental
      malaria does not appear to be associated with cell-mediated immunosuppression.
      The role of the absence of NK cells in increased susceptibility to malaria needs
      to be further elucidated.

PMID- 11237837
TI  - Hypertrophy, hyperplasia, and infectious virus in gut-associated lymphoid tissue
      of mice after oral inoculation with simian-human or bovine-human reassortant
      rotaviruses.
AB  - Oral inoculation of infants with a vaccine that contains simian-human reassortant
      rotaviruses has been found to be a rare cause of intussusception. Because
      intussusception can be associated with enlargement of gut-associated lymphoid
      tissue, we studied the capacity of simian-human and bovine-human reassortant
      rotaviruses to cause lymphoid hypertrophy and hyperplasia of Peyer's patches (PP)
      of adult BALB/c mice. Neither hypertrophy nor hyperplasia was detected in PP
      after oral inoculation with simian-human or bovine-human reassortant rotaviruses.
      However, infectious virus was detected in PP and mesenteric lymph nodes after
      oral inoculation with simian, but not bovine, reassortant rotaviruses.
      Implications of these findings on the pathogenesis of intussusception are
      discussed.

PMID- 11237838
TI  - Impact of human immunodeficiency virus infection on progression to end-stage
      liver disease in individuals with hemophilia and hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) is the major cause of chronic liver disease in
      hemophiliacs. To determine the effect of human immunodeficiency virus (HIV) on
      the natural history of HCV infection, we evaluated end-stage liver disease (ESLD)
      in 157 hemophiliacs (85 HIV positive and 72 HIV negative) with HCV infection for
      an average of 24 years. After adjusting for age at HCV infection, past or current
      hepatitis B surface antigen positivity, and history of alcohol abuse, we
      determined that the rate of ESLD was significantly greater among HIV-positive
      than among HIV-negative hemophiliacs (relative risk [RR], 3.72; 95% confidence
      interval [CI], 1.25-11.09), as was the adjusted RR for death due to ESLD (RR,
      3.81; 95% CI, 1.19-12.16). Among HIV-positive hemophiliacs, crude RR for ESLD was
      lower, but not significantly so, with antiretroviral treatment (RR, 0.19; 95% CI,
      0.03-1.14; P=.069) and increased with each decade of HCV infection (RR, 2.26; 95%
      CI, 1.42-3.59; P=.0006) and HIV infection (RR, 2.18; 95% CI, 1.36-3.49; P=.0013).
      These findings suggest that HIV accelerates HCV disease progression.

PMID- 11237839
TI  - Long-term virologic and immunologic responses in human immunodeficiency virus
      type 1-infected children treated with indinavir, zidovudine, and lamivudine.
AB  - Virologic and immunologic responses were examined for 33 human immunodeficiency
      virus (HIV)-infected children who participated for > or = 96 weeks in a phase 1/2
      protocol of 16 weeks of indinavir monotherapy, followed by the addition of
      zidovudine and lamivudine. At week 96, a median increase of 199 CD4+ T
      cells/microL and a median decrease of 0.74 log(10) HIV RNA copies/mL were
      observed. The relationship between control of viral replication and CD4) T cell
      count was examined. Patients were categorized into 3 response groups on the basis
      of duration and extent of control of viral replication. Of 21 children with a
      transient decrease in virus load of > or = 0.7 log(10) HIV RNA copies/mL from
      baseline, 7 experienced sustained increases in CD4+, CD4+ CD45RA+, and CD4+
      CD45RO+ T cell counts. CD4+ CD45RA+ (naive) T cells were the major contributor to
      CD4+ T cell expansion. Continued long-term immunologic benefit may be experienced
      by a subset of children, despite only transient virologic suppression.

PMID- 11237840
TI  - Human immunodeficiency virus type 1 entry inhibitors PRO 542 and T-20 are
      potently synergistic in blocking virus-cell and cell-cell fusion.
AB  - Human immunodeficiency virus type 1 (HIV-1) entry proceeds via a cascade of
      events that afford promising targets for therapy. PRO 542 neutralizes HIV-1 by
      blocking its attachment to CD4 cells, and T-20 blocks gp41-mediated fusion. Both
      drugs have shown promise in phase 1/2 clinical trials. Here, the drugs were
      tested individually and in combination in preclinical models of HIV-1 infection,
      and inhibition data were analyzed for cooperativity by using the combination
      index method. Synergistic inhibition of virus-cell and cell-cell fusion was
      observed for phenotypically diverse viruses for a broad range of drug
      concentrations, often resulting in > or = 10-fold dose reductions in vitro.
      Additional mechanism-of-action studies probed the molecular basis of the
      synergies. The markedly enhanced activity observed for the PRO 542:T-20
      combination indicates that the multistep nature of HIV-1 entry leaves the virus
      particularly vulnerable to combinations of entry inhibitors. These findings
      provide a strong rationale for evaluating combinations of these promising agents
      for therapy in vivo.

PMID- 11237841
TI  - Hollow-fiber unit evaluation of a new human immunodeficiency virus type 1
      protease inhibitor, BMS-232632, for determination of the linked pharmacodynamic
      variable.
AB  - BMS-232632 is a potent human immunodeficiency type 1 (HIV-1) protease inhibitor
      with a half-life that allows for once-daily dosing. A concentration of 4 times
      the viral 50% effective concentration (EC(50) [i.e., approximately EC(95)])
      administered as a continuous infusion in vitro provides virtually complete
      suppression of viral replication. This exposure, modeled in vitro as once-daily
      administration with oral absorption, allows ongoing viral replication. An
      exposure 4 times as large was calculated to be necessary to provide virus
      suppression equivalent to the continuous-infusion exposure. These experiments
      demonstrated that concentration above a threshold (time > 4xEC50) is the
      pharmacodynamically linked variable for this HIV-1 protease inhibitor. Protein
      binding experiments demonstrated that the EC(50) was increased 13.4 times by the
      addition of human binding proteins. Monte Carlo simulation of protein binding
      adjusted pharmacokinetic data from volunteers demonstrated that 64%-70% of a
      simulated population (n = 3000) would achieve virus suppression with 400-600 mg
      of BMS-232632 given once daily, if the viral EC(50) were < or = 1 nM.

PMID- 11237842
TI  - Human herpesvirus 8 infection and Kaposi's sarcoma among human immunodeficiency
      virus-infected and -uninfected women.
AB  - Little is known about the epidemiology of human herpesvirus 8 (HHV-8) infections
      among women. A cross-sectional study was conducted of HHV-8 infection among human
      immunodeficiency virus (HIV)-infected and high-risk HIV-uninfected women.
      Serological tests with noninduced (latent) and induced (lytic) HHV-8 antigens
      were used to detect infection among 2483 participants of a multisite cohort.
      Reactivity to latent antigen was present in 4.1% and to induced antigens in 12.0%
      of women. Seven of 8 women who reported Kaposi's sarcoma had HHV-8 antibodies.
      Among HIV-positive women, HHV-8 infection was associated with use of crack,
      cocaine, or heroin (76% vs. 65%; P<.001), past syphilis (29% vs. 20%; P<.001), an
      injection drug-using male sex partner (61% vs. 53%; P=.014), black race (P=.010),
      and enrollment site (P=.015). In multivariate analysis, HIV infection, older age,
      past syphilis, black race, and enrollment site were independently associated with
      HHV-8 infection. In this cohort of North American women, HHV-8 infection was
      associated with HIV infection, drug use, and risky sexual behavior.

PMID- 11237843
TI  - False-positive rapid antigen detection test results: reduced specificity in the
      absence of group A streptococci in the upper respiratory tract.
AB  - Rapid antigen detection tests (ADTs) are promoted for identification of group A
      streptococci (GAS) in the upper respiratory tract. Although debate persists about
      their sensitivity, most investigators consider ADTs to be highly specific.
      Nevertheless, reports continue to describe false-positive ADT results (positive
      ADT result, negative culture result). This study examined culture results from
      522 adult patients with acute pharyngitis and a positive ADT result;
      unexpectedly, 15% had throat culture results negative for GAS. Normal bacterial
      flora from 30% of these "negative" culture results produced a positive ADT
      result. An ADT-reactive organism belonging to the Streptococcus milleri group was
      isolated from 1 culture; it carried group A carbohydrate antigen. Although S.
      milleri previously has been associated with false-positive ADT reactions, the
      frequency of this phenomenon is unknown. The present, large study suggests that
      false-positive ADT reactions may be more common than previously reported, an
      observation that must be precisely explained and epidemiologically and clinically
      defined.

PMID- 11237844
TI  - Invasive group B streptococcal disease in Maryland nursing home residents.
AB  - Between 1991 and 1995, among 999 nonpregnant adult Maryland residents with group
      B Streptococcus (GBS) isolated from a normally sterile site, 84 resided in
      nursing homes (NHs). The age-adjusted annual incidence of GBS infection (per
      100,000 population) among those > or = 65 years old was 72.3 for NH residents and
      17.5 for community residents (relative risk, 4.1; P < 0.001). Thirty-four case
      patients resided in 11 NHs with > or = 2 cases; 1 NH had 8 case patients within
      22 months. Six of 8 case patients from 3 NHs had serotype V GBS. Molecular
      subtyping of several isolates identified 2 case patients in 1 NH with identical
      subtype patterns. NH residents have a markedly higher incidence of invasive GBS
      than do community residents > or = 65 years old and may serve as a target group
      for immunization when GBS vaccines become available. Further evaluation of intra
      NH transmission of GBS is warranted.

PMID- 11237845
TI  - Experimental pneumococcal meningitis in mice: a model of intranasal infection.
AB  - Effective laboratory animal models of bacterial meningitis are needed to unravel
      the pathophysiology of this disease. Previous models have failed to simulate
      human meningitis by using a directly intracerebral route of infection.
      Hyaluronidase is a virulence factor of Streptococcus pneumoniae. In this study, a
      novel model of murine meningitis is described. Intranasal administration of S.
      pneumoniae with hyaluronidase induced meningitis in 50% of inoculated mice, as
      defined by a positive cerebrospinal fluid (CSF) culture and an inflammatory
      infiltrate in the meninges. None of the mice inoculated without hyaluronidase
      developed meningitis. Hyaluronidase was found to facilitate pneumococcal invasion
      of the bloodstream after colonization of the upper respiratory tract. Meningitis
      was characterized by pleocytosis of CSF and the induction of proinflammatory
      cytokines and CXC chemokines in brain tissue. These results indicate that this
      murine model mimics important features of human disease and allow for the use of
      this model for studying issues related to the pathophysiology and the treatment
      of pneumococcal meningitis.

PMID- 11237846
TI  - A comparison of Lewis x and Lewis y expression in Helicobacter pylori obtained
      from children and adults.
AB  - There are no reports, to our knowledge, on the expression of Lewis (Le) antigens
      in Helicobacter pylori isolates from children. The aim of this study was to
      compare the expression of Le antigens by H. pylori isolates from children and
      from adults. Totals of 278 clones from 22 children with recurrent abdominal pain
      and 293 clones from 22 adults with (n=10) or without (n=12) duodenal ulcer were
      studied. Expression of Le(x) and Le(y) antigens was determined by ELISA, using
      monoclonal anti-Le antibodies. The Le phenotype of the patients was determined in
      gastric juice with a hemagglutination assay. Clones expressing Le(x) were more
      common in children than in adults (55.4% vs. 33.4%, respectively; P<.001), and
      Le(y) was more common in adults than in children (81.6% vs. 66%, respectively;
      P<.01). A trend analysis showed a significant decline in frequency of clones
      expressing Le(x) with age (P=.021). In this community, expression of Le antigens
      differs in H. pylori isolates obtained from children versus adults.

PMID- 11237847
TI  - Sporadic Campylobacter jejuni infections in Hawaii: associations with prior
      antibiotic use and commercially prepared chicken.
AB  - Campylobacter is the most common cause of bacterial foodborne illness in the
      United States, and Hawaii has the highest rate of Campylobacter jejuni infections
      in the nation. A case-control study was conducted to determine indigenous
      exposures that contribute to the high incidence of sporadic C. jejuni infection
      in Hawaii. A total of 211 case patients with diarrhea and confirmed Campylobacter
      infection was enrolled, along with 1 age- and telephone exchange-matched control
      subject for each patient. Participants were interviewed about illness, medicines,
      food consumption, food-handling practices, and exposure to animals. In matched
      logistic regression analyses, eating chicken prepared by a commercial food
      establishment in the 7 days before case illness onset (adjusted odds ratio [AOR],
      1.8; P=.03) and consuming antibiotics during the 28 days before illness onset
      (AOR, 3.3; P=.03) were significant independent predictors of illness. Further
      study of the association of Campylobacter illness with commercially prepared
      chicken and prior antibiotic use is needed.

PMID- 11237849
TI  - Procalcitonin as a parameter of disease severity and risk of mortality in
      patients with Plasmodium falciparum malaria.
AB  - The serum levels of procalcitonin (PCT) in Plasmodium falciparum malaria were
      evaluated for clinical significance in 66 nonimmune and semi-immune patients. Of
      the 66 patients, 36 had uncomplicated malaria, 24 had severe and complicated
      malaria, and 6 had fatal malaria (5 from previous studies). Pretreatment PCT
      concentrations were closely correlated with parasitemia. Concentrations were
      lowest in semi-immune patients with uncomplicated malaria, compared with those in
      nonimmune patients (geometric mean concentrations [GMCs], 1.07 and 2.37 ng/mL,
      respectively), and were highest in severe and complicated cases (GMC, 10.67
      ng/mL; P<.001 among all subgroups). Six of 7 patients with PCT concentrations >25
      ng/mL died. PCT concentrations decreased on day 2 of treatment in survivors but
      not in patients with fatal outcome. Thus, repeated PCT measurements may provide
      useful prognostic information, especially in medical centers that are not
      experienced in parasite density determination.

PMID- 11237850
TI  - Variants of Plasmodium falciparum erythrocyte membrane protein 1 expressed by
      different placental parasites are closely related and adhere to chondroitin
      sulfate A.
AB  - Plasmodium falciparum-infected erythrocytes adhere to syncytiotrophoblast cells
      lining the placenta via glycosaminoglycans, such as chondroitin sulfate A (CSA)
      and hyaluronic acid. Adherence of infected erythrocytes to host receptors is
      mediated by P. falciparum erythrocyte membrane protein-1 (PfEMP-1). A single
      PfEMP-1 domain (duffy binding-like [DBL]-3, of the gamma sequence class) from
      laboratory-adapted strains is thought to be responsible for binding to CSA. In
      this study, DBL-gamma domains expressed by placental P. falciparum isolates were
      shown to have an affinity to CSA. All parasite populations accumulating in
      infected placentas express only 1 variant of PfEMP-1, each of which contains a
      DBL-gamma domain with CSA binding capacities. Furthermore, sequence analysis data
      provide evidence for antigenic conservation among the DBL-gamma sequences
      expressed by different placental parasites. This study offers a close reflection
      of the process of parasite adhesion in the placenta and is crucial to the
      understanding of the pathogenesis of malaria during pregnancy.

PMID- 11237848
TI  - Typhoid fever and genetic polymorphisms at the natural resistance-associated
      macrophage protein 1.
AB  - Control of Salmonella enterica serovar Typhimurium (S. typhimurium) infection in
      the mouse model of typhoid fever is critically dependent on the natural
      resistance-associated macrophage protein 1 (Nramp1). In this study, we examined
      the role of genetic polymorphisms in the human homologue, NRAMP1, in resistance
      to typhoid fever in southern Vietnam. Patients with blood-culture-confirmed
      typhoid fever and healthy control subjects were genotyped for 6 polymorphic
      markers within and near NRAMP1 on chromosome 2q35. Four single base-pair
      polymorphisms (274 C/T, 469+14 G/C, 1465-85 G/A, and D543N), a (GT)(n) repeat in
      the promoter region of NRAMP1 and D2S1471, and a microsatellite marker
      approximately 130-kb downstream of NRAMP1 were examined. The allelic and
      genotypic frequencies for each polymorphism were compared in case patients and
      control subjects. No allelic association was identified between the NRAMP1
      alleles and typhoid fever susceptibility. In addition, neither homozygotes nor
      heterozygotes for any NRAMP1 variants were at increased risk of typhoid fever.

PMID- 11237851
TI  - Stopped-flow kinetics of locked nucleic acid (LNA)-oligonucleotide duplex
      formation: studies of LNA-DNA and DNA-DNA interactions.
AB  - The locked nucleic acid (LNA) monomer is a conformationally restricted nucleotide
      analogue with an extra 2'-O,4'-C-methylene bridge added to the ribose ring.
      Oligonucleotides that contain LNA monomers have shown greatly enhanced thermal
      stability when hybridized to complementary DNA and RNA and are considered most
      promising candidates for efficient recognition of a given mixed sequence in a
      nucleic acid duplex and as an antisense molecule. Here the kinetics and
      thermodynamics of a series of oligonucleotide duplex formations of DNA-DNA and
      DNA-LNA octamers were studied using stopped-flow absorption measurements at 25
      degrees C and melting curves. The reactions of the DNA octamer 5'-CAGGAGCA-3'
      with its complementary DNA octamer 5'-TGCTCCTG-3', and with the LNA octamers 5'
      T(L)GCTCCTG-3' (LNA-1), 5'-T(L)GCT(L)CCTG-3' (LNA-2) and 5'-T(L)GCT(L)CCT(L)G
      3'(LNA-3), containing respectively one, two or three thymidine 2'-O,4'-C
      methylene-(D-ribofuranosyl) nucleotide monomers, designated T(L), were studied.
      In all cases were seen fast second-order association reactions with
      k(obs)=2x10(7) M(-1)s(-1). At 25 degrees C the dissociation constants of the
      duplexes obtained from melting curves were: DNA-DNA, 10 nM; DNA-LNA-1, 20 nM; DNA
      LNA-2, 2 nM; and DNA-LNA-3, 0.3 nM; thus the greatly enhanced duplex stability
      induced by LNA is confirmed. Since the association rates were all equal this
      increase in stability is due to slower rates of dissociation of the complexes.

PMID- 11237852
TI  - Tyr199 in transmembrane domain 5 of the beta2-adrenergic receptor interacts
      directly with the pharmacophore of a unique fluorenone-based antagonist.
AB  - Mutagenesis of the beta2-adrenergic receptor (beta2AR) has suggested that amino
      acids in transmembrane domain 5 (TMD 5) play an important role in the interaction
      of the receptor with the catechol end of adrenergic agonists. However, little
      direct biochemical evidence for the interaction of any beta2AR agonist or
      antagonist with TMD 5 has been reported. To identify receptor amino acids that
      contribute to the beta2AR antagonist binding site, we identified the precise
      amino acid photoinsertion site of a novel carazolol-like fluorenone antagonist
      photoaffinity label, [125I]iodoaminoflisopolol ([125I]IAmF). A unique property of
      this photolabel is that the photoreactive centre is also the binding
      pharmacophore, which corresponds to the catechol end of related beta2AR agonists.
      [125I]IAmF specifically photolabels membrane-bound and purified beta2AR from a
      baculovirus/Spodoptera frugiperda (fall armyworm) ('Sf9') expression system. When
      the photolabelled beta2AR was cleaved by trypsin or Factor Xa, 30 kDa labelled
      peptides were generated. On the basis of concanavalin A binding and amino acid
      sequencing, these contain the N-terminus of the beta2AR, including TMDs 1-5.
      Further cleavage of the 30 kDa peptides with endoproteinase Lys-C generated a 4
      kDa labelled peptide with an N-terminal amino acid sequence between TMDs 4 and 5.
      Radiosequencing of this peptide demonstrated that the precise [125I]IAmF
      photoinsertion site was Tyr(199) in TMD 5. Since the photoreactive centre and the
      binding pharmacophore of IAmF are the same, these data demonstrate that Tyr(199)
      interacts with the planar fluorenone moiety of a carazolol-like beta2AR
      antagonist, and contributes significant new information regarding the binding
      site for beta2AR antagonists.

PMID- 11237853
TI  - Epicatechin and its in vivo metabolite, 3'-O-methyl epicatechin, protect human
      fibroblasts from oxidative-stress-induced cell death involving caspase-3
      activation.
AB  - There is considerable current interest in the cytoprotective effects of natural
      antioxidants against oxidative stress. In particular, epicatechin, a major member
      of the flavanol family of polyphenols with powerful antioxidant properties in
      vitro, has been investigated to determine its ability to attenuate oxidative
      stress-induced cell damage and to understand the mechanism of its protective
      action. We have induced oxidative stress in cultured human fibroblasts using
      hydrogen peroxide and examined the cellular responses in the form of
      mitochondrial function, cell-membrane damage, annexin-V binding and caspase-3
      activation. Since one of the major metabolites of epicatechin in vivo is 3'-O
      methyl epicatechin, we have compared its protective effects with that of
      epicatechin. The results provide the first evidence that 3'-O-methyl epicatechin
      inhibits cell death induced by hydrogen peroxide and that the mechanism involves
      suppression of caspase-3 activity as a marker for apoptosis. Furthermore, the
      protection elicited by 3'-O-methyl epicatechin is not significantly different
      from that of epicatechin, suggesting that hydrogen-donating antioxidant activity
      is not the primary mechanism of protection.

PMID- 11237854
TI  - Human ornithine transcarbamylase: crystallographic insights into substrate
      recognition and conformational changes.
AB  - Two crystal structures of human ornithine transcarbamylase (OTCase) complexed
      with the substrate carbamoyl phosphate (CP) have been solved. One structure,
      whose crystals were prepared by substituting N-phosphonacetyl-L-ornithine (PALO)
      liganded crystals with CP, has been refined at 2.4 A (1 A=0.1 nm) resolution to a
      crystallographic R factor of 18.4%. The second structure, whose crystals were
      prepared by co-crystallization with CP, has been refined at 2.6 A resolution to a
      crystallographic R factor of 20.2%. These structures provide important new
      insights into substrate recognition and ligand-induced conformational changes.
      Comparison of these structures with the structures of OTCase complexed with the
      bisubstrate analogue PALO or CP and L-norvaline reveals that binding of the first
      substrate, CP, induces a global conformational change involving relative domain
      movement, whereas the binding of the second substrate brings the flexible SMG
      loop, which is equivalent to the 240s loop in aspartate transcarbamylase, into
      the active site. The model reveals structural features that define the substrate
      specificity of the enzyme and that regulate the order of binding and release of
      products.

PMID- 11237855
TI  - Natural-resistance-associated macrophage protein 1 is an H+/bivalent cation
      antiporter.
AB  - In mammals, natural-resistance-associated macrophage protein 1 (Nramp1) regulates
      macrophage activation and is associated with infectious and autoimmune diseases.
      Nramp2 is associated with anaemia. Both belong to a highly conserved
      eukaryote/prokaryote protein family. We used Xenopus oocytes to demonstrate that,
      like Nramp2, Nramp1 is a bivalent cation (Fe2+, Zn2+ and Mn2+) transporter.
      Strikingly, however, where Nramp2 is a symporter of H+ and metal ions, Nramp1 is
      a highly pH-dependent antiporter that fluxes metal ions in either direction
      against a proton gradient. At pH 9.0, oocytes injected with cRNA from wild-type
      murine Nramp1 with a glycine residue at position 169 (Nramp1(G169); P=3.22x10(
      6)) and human NRAMP1 (P=3.87x10(-5)) showed significantly enhanced uptake of
      radiolabelled Zn2+ compared with water-injected controls. At pH 5.5, Nramp1(G169)
      (P=1.34x10(-13)) and NRAMP1 (P=1.09x10(-6)) oocytes showed significant efflux of
      Zn2+. Zn2+ transport was abolished when the proton gradient was dissipated using
      carbonyl cyanide p-trifluoromethoxyphenylhydrazone. Using pre-acidified oocytes,
      currents of 130+/-57 nA were evoked by 100 microM Zn2+ at pH 7.5, and 139+/-47 nA
      by 100 microM Fe2+ at pH 7.0, in Nramp1(G169) oocytes; currents of 254+/-49 nA
      and 242+/-26 nA were evoked, respectively, in NRAMP1 oocytes. Steady-state
      currents evoked by increasing concentrations of Zn2+ were saturable, with
      apparent affinity constants of approx. 614 nM for Nramp1(G169) and approx. 562 nM
      for NRAMP1 oocytes, and a curvilinear voltage dependence of transporter activity
      (i.e. the data points approximate to a curve that approaches a linear asymptote).
      In the present study we propose a new model for metal ion homoeostasis in
      macrophages. Under normal physiological conditions, Nramp2, localized to early
      endosomal membranes, delivers extracellularly acquired bivalent cations into the
      cytosol. Nramp1, localized to late endosomal/lysosomal membranes, delivers
      bivalent cations from the cytosol into this acidic compartment where they may
      directly affect antimicrobial activity.

PMID- 11237856
TI  - Expression pattern and localization of beta,beta-carotene 15,15'-dioxygenase in
      different tissues.
AB  - Beta,beta-carotene 15,15'-dioxygenase cleaves beta,beta-carotene into two
      molecules of retinal, and is the key enzyme in the metabolism of beta,beta
      carotene to vitamin A. The enzyme has been known for more than 40 years, yet all
      attempts to purify the protein to homogeneity have failed. Recently, the
      successful cloning and sequencing of an enzyme with beta,beta-carotene 15,15'
      dioxygenase activity from chicken, as well as from Drosophila, has been reported.
      Here, we describe in detail our attempt to enrich the chicken beta,beta-carotene
      15,15'-dioxygenase to such an extent as to allow determination of partial amino
      acid sequences, which were then used to design degenerate oligonucleotides.
      Screening of a chicken duodenal expression library yielded a full-length clone
      containing a coding sequence of 1578 bp. Functional expression in Escherichia
      coli and in eukaryotic cell lines confirmed that we had cloned the first
      vertebrate dioxygenase that cleaves beta,beta-carotene at the central 15,15'
      double bond. By performing a sequence homology search, the cDNA sequence of the
      mouse homologue was found as an expressed sequence tag (EST) in the gene bank. At
      the amino-acid level, the degree of homology between the chicken and mouse
      sequences is 81%. Thus beta,beta-carotene 15,15'-dioxygenase can be considered as
      being an enzyme that is evolutionarily rather well conserved. We established the
      expression pattern of beta,beta-carotene 15,15'-dioxygenase in chicken and mouse
      tissues with a combination of Northern blots and in situ hybridization. The mRNA
      for beta,beta-carotene 15,15'-dioxygenase was localized primarily in duodenal
      villi, as well as in liver and in tubular structures of lung and kidney. These
      new findings demonstrate that beta,beta-carotene 15,15'-dioxygenase is also
      expressed in epithelial structures, where it serves to provide the tissue
      specific vitamin A supply.

PMID- 11237857
TI  - Perivenous expression of the mRNA of the three hypoxia-inducible factor alpha
      subunits, HIF1alpha, HIF2alpha and HIF3alpha, in rat liver.
AB  - The cDNAs of three hypoxia-inducible factor (HIF) alpha-subunits were cloned from
      RNA of primary rat hepatocytes by reverse transcriptase PCR. All three cDNAs
      encoded functionally active proteins, of 825, 874 and 662 amino acids. After
      transfection they were able to activate luciferase activity of a luciferase gene
      construct containing three HIF-responsive elements. The mRNAs of the rat HIF
      alpha-subunits were expressed predominantly in the perivenous zone of rat liver
      tissue; the nuclear HIFalpha proteins, however, did not appear to be zonated.

PMID- 11237859
TI  - The pancreas-specific protein disulphide-isomerase PDIp interacts with a
      hydroxyaryl group in ligands.
AB  - Using a cross-linking approach, we have recently demonstrated that radiolabelled
      model peptides or misfolded proteins specifically interact in vitro with two
      members of the protein disulphide- isomerase family, namely PDI and PDIp, in a
      crude extract from sheep pancreas microsomes. In addition, we have shown that
      tyrosine and tryptophan residues within a peptide are the recognition motifs for
      the binding to PDIp. Here we examine non-peptide ligands and present evidence
      that a hydroxyaryl group is a structural motif for the binding to PDIp; simple
      constructs containing this group and certain xenobiotics and phytoestrogens,
      which contain an unmodified hydroxyaryl group, can all efficiently inhibit
      peptide binding to PDIp. To our knowledge this is the first time that the
      recognition motif of a molecular chaperone or folding catalyst has been specified
      as a simple chemical structure.

PMID- 11237858
TI  - The effect of Mg2+ on cardiac muscle function: Is CaATP the substrate for priming
      myofibril cross-bridge formation and Ca2+ reuptake by the sarcoplasmic reticulum?
AB  - Kinetics are established for the activation of the myofibril from the relaxed
      state [Smith, Dixon, Kirschenlohr, Grace, Metcalfe and Vandenberg (2000) Biochem.
      J. 346, 393-402]. These require two troponin Ca2+-binding sites, one for each
      myosin head, to act as a single unit in initial cross-bridge formation. This
      defines the first, or activating, ATPase reaction, as distinct from the further
      activity of the enzyme that continues when a cross-bridge to actin is already
      established. The pairing of myosin heads to act as one unit suggests a possible
      alternating mechanism for muscle action. A large positive inotropic (contraction
      intensifying) effect of loading the Mg2+ chelator citrate, via its acetoxymethyl
      ester, into the heart has confirmed the competitive inhibition of the Ca2+
      activation by Mg2+, previously seen in vitro. In the absence of a recognized
      second Ca2+ binding site on the myofibril, with appropriate binding properties,
      the bound ATP is proposed as the second activating Ca2+-binding site. As ATP,
      free or bound to protein, can bind either Mg2+ or Ca2+, this leads to competitive
      inhibition by Mg2+. Published physico-chemical studies on skeletal muscle have
      shown that CaATP is potentially a more effective substrate than MgATP for cross
      bridge formation. The above considerations allow calculation of the observed
      variation of fractional activation by Ca2+ as a function of [Mg2+] and in turn
      reveal simple Michaelis-Menten kinetics for the activation of the ATPase by sub
      millimolar [Mg2+]. Furthermore the ability of bound ATP to bind either cation,
      and the much better promotion of cross-bridge formation by CaATP binding, give
      rise to the observed variation of the Hill coefficient for Ca2+ activation with
      altered [Mg2+]. The inclusion of CaADP within the initiating cross-bridge and
      replacement by MgADP during the second cycle is consistent with the observed fall
      in the rate of the myofibril ATPase that occurs after two phosphates are
      released. The similarity of the kinetics of the cardiac sarcoplasmic reticulum
      ATPase to those of the myofibril, in particular the positive co-operativity of
      both Mg2+ inhibition and Ca2+ activation, leads to the conclusion that this
      ATPase also has an initiation step that utilizes CaATP. The first-order
      activation by sub-millimolar [Mg2+], similar to that of the myofibril, may be
      explained by Mg2+ involvement in the phosphate-release step of the ATPase. The
      inhibition of both the myofibril and sarcoplasmic reticulum Ca2+ transporting
      ATPases by Mg2+ offers an explanation for the specific requirement for
      phosphocreatine (PCr) for full activity of both enzymes in situ and its effect on
      their apparent affinities for ATP. This explanation is based on the slow
      diffusion of Mg2+ within the myofibril and on the contrast of PCr with both ATP
      and phosphoenolpyruvate, in that PCr does not bind Mg2+ under physiological
      conditions, whereas both the other two bind it more tightly than the products of
      their hydrolysis do. The switch to supply of energy by diffusion of MgATP into
      the myofibril when depletion of PCr raises [ATP]/[PCr] greatly, e.g. during
      anoxia, results in a local [Mg2+] increase, which inhibits the ATPase. It is
      possible that mechanisms similar to those described above occur in skeletal
      muscle but the Ca2+ co-operativity involved would be masked by the presence of
      two Ca2+ binding sites on each troponin.

PMID- 11237861
TI  - Thyrotropin modifies activation of nuclear factor kappaB by tumour necrosis
      factor alpha in rat thyroid cell line.
AB  - We have recently demonstrated that nuclear factor kappaB (NF-kappaB) mediates the
      tumour necrosis factor alpha (TNF-alpha)-dependent expression of the gene
      encoding interleukin 6 (IL-6) in rat thyroid FRTL-5 cells cultured in the
      presence of thyrotropin (TSH). In the present study we investigated how TSH is
      involved in the activation of NF-kappaB by TNF-alpha in the cells.
      Electrophoretic mobility-shift assay revealed that, in the absence of TSH, TNF
      alpha activated a single protein-DNA complex containing the p50 subunit but not
      other NF-kappaB subunits such as p65. In contrast, two distinct protein-DNA
      complexes were activated in the presence of TSH: the faster-migrating complex
      contained only p50 subunit; the slower-migrating complex consisted of p65-p50
      heterodimer. This TSH effect was mimicked by forskolin and thyroid-stimulating
      antibodies obtained from patients with Graves's disease, suggesting that an
      increase in intracellular cAMP is responsible for the induction of different NF
      kappaBs by TNF-alpha. A transient transfection study with a luciferase reporter
      gene driven by multimerized NF-kappaB sites demonstrated that TNF-alpha increased
      the luciferase activities only in the presence of TSH, and that this increase was
      inhibited by the co-transfection of mutant p65, which prevented the function of
      wild-type p65 in a dominant-negative manner. Accordingly, TNF-alpha activated the
      expression of the IL-6 gene in the presence of TSH but not in its absence.
      Although the expression of the p105 gene, another known target for NF-kappaB, was
      increased by TNF-alpha in the absence of TSH, the presence of TSH further
      increased the mRNA level. Taken together, these observations indicate that the
      presence of TSH is crucial for the NF-kappaB-mediated actions of TNF-alpha on
      thyroid follicular cells.

PMID- 11237860
TI  - Multiple endocytic signals in the C-terminal tail of the cystic fibrosis
      transmembrane conductance regulator.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP
      dependent protein kinase (PKA)-activated chloride channel that is localized to
      the plasma membrane and endosomal compartment. Endosomal targeting of CFTR is
      attributed to the Tyr(1424)-based internalization signal, identified in the C
      terminal tail of the channel. Mutation of the Tyr(1424) residue could partly
      inhibit the endocytosis of CFTR and its association with the adapter protein AP
      2. To reveal additional endosomal targeting signals, site-directed mutagenesis of
      both a chimaera, composed of a truncated form of interleukin 2 receptor alpha
      chain (TacT) and the C-terminal tail of CFTR (Ct), and the full-length CFTR was
      performed. Morphological and functional assays revealed the presence of multiple
      internalization motifs at the C-terminus, consisting of a phenylalanine-based
      motif (Phe(1413)) and a bipartite endocytic signal, comprising a tyrosine
      (Tyr(1424)) and a di-Leu-based (Leu(1430)-Leu) motif. Whereas the replacement of
      any one of the three internalization motifs with alanine prevented the
      endocytosis of the TacT-Ct chimaera, mutagenesis of Phe(1413)-Leu impaired the
      biosynthetic processing of CFTR, indicating that Phe(1413) is indispensable for
      the native structure of CFTR. In contrast, replacement of Leu(1430)-Leu- and
      Tyr(1424)-based signals with alanine increased the cell-surface density of both
      the chimaeras and CFTR in an additive manner. These results suggest that the
      internalization of CFTR is regulated by multiple endocytic sorting signals.

PMID- 11237862
TI  - Comparative study of protein tyrosine phosphatase-epsilon isoforms: membrane
      localization confers specificity in cellular signalling.
AB  - To study the influence of subcellular localization as a determinant of signal
      transduction specificity, we assessed the effects of wild-type transmembrane and
      cytoplasmic protein tyrosine phosphatase (PTP) epsilon on tyrosine kinase
      signalling in baby hamster kidney (BHK) cells overexpressing the insulin receptor
      (BHK-IR). The efficiency by which differently localized PTPepsilon and PTPalpha
      variants attenuated insulin-induced cell rounding and detachment was determined
      in a functional clonal-selection assay and in stable cell lines. Compared with
      the corresponding receptor-type PTPs, the cytoplasmic PTPs (cytPTPs) were
      considerably less efficient in generating insulin-resistant clones, and
      exceptionally high compensatory expression levels were required to counteract
      phosphotyrosine-based signal transduction. Targeting of cytPTPepsilon to the
      plasma membrane via the Lck-tyrosine kinase dual acylation motif restored high
      rescue efficiency and abolished the need for high cytPTPepsilon levels.
      Consistent with these results, expression levels and subcellular localization of
      PTPepsilon were also found to determine the phosphorylation level of cellular
      proteins including focal adhesion kinase (FAK). Furthermore, PTPepsilon
      stabilized binding of phosphorylated FAK to Src, suggesting this complex as a
      possible mediator of the PTPepsilon inhibitory response to insulin-induced cell
      rounding and detachment in BHK-IR cells. Taken together, the present localization
      function study indicates that transcriptional control of the subcellular
      localization of PTPepsilon may provide a molecular mechanism that determines
      PTPepsilon substrate selectivity and isoform-specific function.

PMID- 11237863
TI  - Cyclosporin A reduces canalicular membrane fluidity and regulates transporter
      function in rats.
AB  - Changes of the biliary canalicular membrane lipid content can affect membrane
      fluidity and biliary lipid secretion in rats. The immunosuppressant cyclosporin A
      is known to cause intrahepatic cholestasis. This study investigated whether
      cyclosporin A influenced canalicular membrane fluidity by altering membrane
      phospholipids or transporter expression. In male Sprague-Dawley rats, a bile-duct
      cannula was inserted to collect bile, and sodium taurocholate was infused (100
      nmol/min per 100 g) for 60 min. During steady-state taurocholate infusion,
      cyclosporin A (20 mg/kg) or vehicle was injected intravenously and then bile was
      collected for 80 min. After killing the rats, canalicular membrane vesicles were
      prepared. Expression of canalicular membrane transporters was assessed by Western
      blotting and canalicular membrane vesicle fluidity was estimated by fluorescence
      polarization. Cyclosporin A reduced biliary lipid secretion along with a
      disproportionate reduction of lipids relative to bile acids. Cyclosporin A
      significantly decreased canalicular membrane fluidity along with an increase of
      the cholesterol/phospholipid molar ratio. Only expression of the transporter P
      glycoprotein was increased by cyclosporin A. Because canalicular membrane
      transporter expression was largely unchanged by cyclosporin A despite a marked
      decrease of biliary lipid secretion, transporter activity may partly depend upon
      canalicular membrane fluidity.

PMID- 11237864
TI  - Molecular interaction of dihydropyridine receptors with type-1 ryanodine
      receptors in rat brain.
AB  - In striated muscles, Ca2+ release from internal stores through ryanodine receptor
      (RyR) channels is triggered by functional coupling to voltage-activated Ca2+
      channels known as dihydropyridine receptors (DHPRs) located in the plasma
      membrane. In skeletal muscle, this occurs by a direct conformational link between
      the tissue-specific DHPR (Ca(v)1.1) and RyR(1), whereas in the heart the signal
      is carried from the cardiac-type DHPR (Ca(v)1.2) to RyR(2) by calcium ions acting
      as an activator. Subtypes of both channels are expressed in the central nervous
      system, but their functions and mechanisms of coupling are still poorly
      understood. We show here that complexes immunoprecipitated from solubilized rat
      brain membranes with antibodies against DHPR of the Ca(v)1.2 or Ca(v)1.3 subtypes
      contain RyR. Only type-1 RyR is co-precipitated, although the major brain isoform
      is RyR(2). This suggests that, in neurons, DHPRs could communicate with RyRs by
      way of a strong molecular interaction and, more generally, that the physical link
      between DHPR and RyR shown to exist in skeletal muscle can be extended to other
      tissues.

PMID- 11237865
TI  - Roles of the forkhead in rhabdomyosarcoma (FKHR) phosphorylation sites in
      regulating 14-3-3 binding, transactivation and nuclear targetting.
AB  - The transcription factor, forkhead in rhabdomyosarcoma (FKHR), is phosphorylated
      at three amino acid residues (Thr-24, Ser-256 and Ser-319) by protein kinase B
      (PKB)alpha. In the present study, mutagenesis has been used to study the roles of
      these phosphorylation events in regulating FKHR function in transfected HEK-293
      cells. We find that the overexpression of FKHR[S256A] (where Ser-256-->Ala)
      blocks PKB activity in cells, preventing phosphorylation of the endogenous
      substrates FKHRL1 and glycogen synthase kinase-3. Thus some reported effects of
      overexpression of this and other mutants may be indirect, and result from
      suppression of the phosphorylation of other sites on FKHR and/or other PKB
      substrates. For example, we have shown that Thr-24 phosphorylation alone is
      critical for interaction with 14-3-3 proteins, and that the substitution of Ser
      256 with an alanine residue indirectly blocks 14-3-3 protein binding by
      preventing the phosphorylation of Thr-24. We also found that insulin-like growth
      factor (IGF)-1 and serum-induced nuclear exclusion of FKHR[S256A] depends on the
      degree of overexpression of this mutant. Our results indicated that the
      interaction of FKHR with 14-3-3 proteins was not required for IGF-1-stimulated
      exclusion of FKHR from the nucleus. We present evidence in support of another
      mechanism, which depends on the phosphorylation of Ser-256 and may involve the
      masking of a nuclear localization signal. Finally, we have demonstrated that the
      failure of IGF-1 to suppress transactivation by FKHR[S256A] is not explained
      entirely by its failure to bind 14-3-3 proteins or to undergo nuclear exclusion.
      This result suggests that Ser-256 phosphorylation may also suppress
      transactivation by FKHR by yet another mechanism, perhaps by disrupting the
      interaction of FKHR with target DNA binding sites and/or the function of the
      transactivation domain.

PMID- 11237866
TI  - Effect of human acetylcholinesterase subunit assembly on its circulatory
      residence.
AB  - Sialylated recombinant human acetylcholinesterase (rHuAChE), produced by stably
      transfected cells, is composed of a mixed population of monomers, dimers and
      tetramers and manifests a time-dependent circulatory enrichment of the higher
      order oligomeric forms. To investigate this phenomenon further, homogeneous
      preparations of rHuAChE differing in their oligomerization statuses were
      generated: (1) monomers, represented by the oligomerization-impaired C580A
      rHuAChE mutant, (2) wild-type (WT) dimers and (3) tetramers of WT-rHuAChE
      generated in vitro by complexation with a synthetic ColQ-derived proline-rich
      attachment domain ('PRAD') peptide. Three different series of each of these three
      oligoform preparations were produced: (1) partly sialylated, derived from HEK-293
      cells; (2) fully sialylated, derived from engineered HEK-293 cells expressing
      high levels of sialyltransferase; and (3) desialylated, after treatment with
      sialidase to remove sialic acid termini quantitatively. The oligosaccharides
      associated with each of the various preparations were extensively analysed by
      matrix-assisted laser desorption ionization-time-of-flight MS. With the enzyme
      preparations comprising the fully sialylated series, a clear linear relationship
      between oligomerization and circulatory mean residence time (MRT) was observed.
      Thus monomers, dimers and tetramers exhibited MRTs of 110, 195 and 740 min
      respectively. As the level of sialylation decreased, this differential behaviour
      became less pronounced; eventually, after desialylation all oligoforms had the
      same MRT (5 min). These observations suggest that multiple removal systems
      contribute to the elimination of AChE from the circulation. Here we also
      demonstrate that by the combined modulation of sialylation and tetramerization it
      is possible to generate a rHuAChE displaying a circulatory residence exceeding
      that of all other known forms of native or recombinant human AChE.

PMID- 11237867
TI  - Affinity of mismatch-binding protein MutS for heteroduplexes containing different
      mismatches.
AB  - We have used bandshift analysis to measure the interaction between the
      Escherichia coli mismatch-binding protein MutS and synthetic DNA fragments
      containing all possible DNA mismatches as well as an unpaired T (DeltaT). The
      order of affinity is found to be DeltaT>GT>GG>AA approximately TT approximately
      TC>CA>GA>CC>GC. We find that the affinity for GT mismatches is affected by the
      flanking sequence and decreases in the order G(n)C(n)>(GC)(n)>A(n)T(n)>(AT)(n).
      Studies with base analogues show good binding to phiT (where phi represents 1',2'
      dideoxyribose), but much weaker binding to Gphi.

PMID- 11237868
TI  - Mitogen-stimulated TIS21 protein interacts with a protein-kinase-Calpha-binding
      protein rPICK1.
AB  - TIS21 is induced transiently by PMA and a number of extracellular stimuli. Yeast
      two-hybrid screening has identified three TIS21 interacting clones from a rat
      cDNA library [Lin, Gary, Yang, Clarke and Herschman (1996) J. Biol. Chem 271,
      15034-15044]. The amino acid sequence deduced from clone 5A shows 96.9% identity
      with the murine PICK1, a protein kinase Calpha (PKCalpha)-binding protein
      postulated to act as an intracellular receptor for PKC. A fusion protein of
      glutathione S-transferase and rPICK1 associates with the TIS21 translated in
      vitro, suggesting a direct physical interaction between these two proteins. TIS21
      and rPICK1 are co-immunoprecipitated from NIH 3T3 cells overexpressing these two
      proteins. This indicates that the interaction also occurs in mammalian cells.
      Deletion of the PDZ domain at the N-terminus of rPICK1 abolishes its interaction
      with TIS21. A putative carboxylate-binding loop required for PICK1 to bind
      PKCalpha [Staudinger, Lu and Olson (1997) J. Biol. Chem 272, 32019-32024] is
      within this deleted region. Our results suggest a potential competition between
      TIS21 and PKC for binding to PICK1. We show that recombinant TIS21 is
      phosphorylated by PKC in vitro. The catalytic activity of PKC towards TIS21 is
      significantly decreased in the presence of rPICK1, whereas phosphorylation of
      histone by PKC is not affected. rPICK1 seems to modulate the phosphorylation of
      TIS21 through specific interactions between these two proteins. TIS21 might have
      a role in PKC-mediated extracellular signal transduction through its interaction
      with rPICK1.

PMID- 11237869
TI  - Differential expression of chicken dimerization cofactor of hepatocyte nuclear
      factor-1 (DcoH) and its novel counterpart, DcoHalpha.
AB  - We have used differential display PCR to study altered gene expression in
      immortalized chicken embryo fibroblasts (CEFs) that have been established in our
      laboratory. This technique resulted in the cloning of a novel counterpart of the
      previously cloned chicken dimerization cofactor of hepatocyte nuclear factor
      (HNF)-1 (cDcoH), which was identified as cDcoHalpha. The steady-state mRNA levels
      of cDcoHalpha were up-regulated in all immortal CEFs tested compared with primary
      CEF cells. cDcoH and cDcoHalpha showed opposite patterns of mRNA expression due
      to differential regulation of transcription rates, but not mRNA half-lives, in
      primary and immortal CEFs. Expression of cDcoHalpha increased in the late G1 and
      early S phases of the cell cycle, while cDcoH mRNA increased in the late S and
      G2/M phases. In contrast with consistent expression of both genes in primary
      quiescent cells, cDcoH mRNA, but not cDcoHalpha mRNA, was dramatically decreased
      in primary senescent cells. The highest levels of cDcoHalpha mRNA were found in
      the kidney, liver, heart and ovarian follicles, while the major tissues
      expressing cDcoH were hypothalamus, kidney and liver. cDcoH and cDcoHalpha probes
      did not cross-hybridize to human hepatocyte mRNA. When transfected into human
      HepG2 cells, both cDcoH and cDcoHalpha showed similar functional activity as
      measured by increased expression of a reporter gene, as well as alpha-fetoprotein
      and albumin genes that both contain HNF-1 binding elements in their promoters.
      Our results suggest that the novel chicken DcoHalpha might function as a
      transcriptional cofactor for HNF-1 in specific cellular-environmental states.

PMID- 11237870
TI  - Identification of Cdc6 protein domains involved in interaction with Mcm2 protein
      and Cdc4 protein in budding yeast cells.
AB  - The Cdc6 protein (Cdc6p) has essential roles in regulating initiation of DNA
      replication. Cdc6p is recruited to origins of replication by the origin
      recognition complex (ORC) late in mitosis; Cdc6p in turn recruits minichromosome
      maintenance (Mcm) proteins to form the pre-replicative complex. Cdc6p is thought
      to interact with one or more Mcm proteins but this point has not yet been
      demonstrated. In the present study we observed that Cdc6p interacted
      significantly only with Mcm2p out of six Mcm proteins in yeast two-hybrid cells.
      Our results indicate that the interaction of Cdc6p with Mcm2p is specific,
      although we cannot exclude the possibility that the interaction might not be
      direct. In attempts to identify domains of Cdc6p important for interaction with
      Mcm2p, we tested interactions of various deleted versions of Cdc6p with Mcm2p and
      also with Cdc4p, which was previously known to interact with Cdc6p. The portion
      of Cdc6p from amino acid residues 51 to 394 was able to interact with Mcm2p.
      During the course of the studies we also discovered a previously undetected Cdc4p
      interaction domain between residues 51 and 394. Interestingly, when all six
      putative Cdc28 phosphorylation sites in Cdc6p were changed to alanine, a 6-7-fold
      increase in binding to Mcm2p was observed. This result suggests that
      unphosphorylated Cdc6p has higher affinity than phosphorylated Cdc6p for Mcm2p;
      this might partly explain the previous observation that Cdc6p failed to load Mcm
      proteins on replication origins during S phase when the cyclin-dependent protein
      kinase was active, thus helping to prevent the reinitiation of activated
      replicons.

PMID- 11237871
TI  - Substrate-binding characteristics of proteins in the 90 kDa heat shock protein
      family.
AB  - In the present study we investigated the substrate-binding characteristics of
      three members of the 90 kDa heat shock protein (HSP90) family, namely the alpha
      isoform of human HSP90 (HSP90alpha), human GRP94 (94 kDa glucose-regulated
      protein, a form of HSP90 from endoplasmic reticulum), and HtpG (the Escherichia
      coli homologue of HSP90) and the domain responsible for these characteristics.
      The recombinant forms of HSP90alpha, GRP94 and HtpG existed as dimers and became
      oligomerized at higher temperatures. Among the three family members, HtpG
      required the highest temperature (65 degrees C) for its transition to oligomeric
      forms. The precipitation of the substrate protein, glutathione S-transferase,
      which occurred at 55 degrees C, was efficiently prevented by the simultaneous
      presence of a sufficient amount of HSP90alpha or GRP94, but not by HtpG, which
      was still present as a dimer at that temperature. However, precipitation was
      stopped completely at 65-70 degrees C, at which temperature HtpG was
      oligomerized. Thus the transition of HSP90-family proteins to a state with self
      oligomerization ability is essential for preventing the precipitation of
      substrate proteins. We then investigated the domain responsible for the substrate
      binding of HtpG on the basis of the three domain structures. The self
      oligomerizing and substrate-binding activities towards glutathione S-transferase
      and citrate synthase were both located in a single domain, the N-terminal domain
      (residues 1-336) of HtpG. We therefore propose that the primary peptide-binding
      site is located in the N-terminal domain of HSP90-family proteins.

PMID- 11237872
TI  - Delivery of oligonucleotides into mammalian cells by anionic peptides: comparison
      between monomeric and dimeric peptides.
AB  - The use of antisense oligonucleotides as putative therapeutic agents is limited
      by their poor delivery into the cytosol and/or the nucleus because they are not
      able to efficiently cross lipid bilayers. To circumvent this pitfall, anionic
      amphipathic peptides derived from the influenza virus fusogenic peptide have been
      used to destabilize membranes in an acidic environment. In this paper, we compare
      the ability of a monomeric and a dimeric peptide to introduce oligonucleotides
      into the cytosol and nuclei of several types of cultured cells. Cells incubated
      at pH 6.2 or at a slightly lower pH in the presence of the monomeric peptide but
      not the dimeric peptide were efficiently permeabilized. The location of
      fluorescent derivatives of peptides and of oligonucleotides was assessed by
      confocal microscopy. Both the peptides and oligonucleotides remained entrapped in
      vesicular compartments at neutral pH; at acidic pH, oligonucleotides in the
      presence of the monomeric peptide were mainly in the nucleus, while in the
      presence of the dimeric peptide they co-localized with the peptide into vesicles.
      The data are interpreted on the basis of the spectroscopic behaviour of monomeric
      and dimeric peptides in relation to the environmental pH.

PMID- 11237873
TI  - Phosphatidic acid-phosphatidylethanolamine interaction and apocytochrome c
      translocation across model membranes.
AB  - The translocation of apocytochrome c (apocyt.c) across large unilamellar vesicles
      (LUVs) constructed from mixtures of anionic and zwitterionic phospholipids,
      phosphatidylethanolamine (PE) and phosphatidylcholine (PC), has been studied. It
      was shown that the import ratio of horse heart apocyt.c in LUVs composed of
      phosphatidic acid (PA) combined with PE and PC (62+/-10%) was much higher than
      that in LUVs made of PE and PC plus any other acidic phospholipid species (20+/
      5%). This feature was shared by tuna heart and chicken heart apocyt.c. In
      addition, the greater efficiency of the PA/PE/PC system versus others in
      facilitating apocyt.c translocation was maintained using synthetic anionic
      phospholipids with the same acyl chains. Besides, apocyt.c induces more leakage
      of entrapped fluorescein sulphonate (FS) from the interior of PA/PC/PE vesicles
      compared with phosphatidylglycerol (PG)/PC/PE ones. By measuring the intrinsic
      fluorescence emission spectrum and the accessibility of the preprotein to the
      fluorescence quencher, acrylamide, differences could be detected in the
      conformational changes of apocyt.c as a consequence of its interaction with
      PA/PE/PC and PG/PE/PC vesicles, respectively. Particularly notable is that PE is
      indispensable for the PA/PE/PC system to most efficiently facilitate apocyt.c
      translocation across the model membranes. With the fraction of PE increasing from
      0 to 30 mol%, the translocation efficiency of apocyt.c as well as its ability to
      induce FS efflux was significantly enhanced in PA-containing LUVs, whereas this
      was not observed in the case of replacement of PA by PG or phosphatidylserine. It
      is also interesting to note that in LUVs containing PA, dioleoyl-PE, but not
      dielaidoyl-PE, can exert such influences, indicative of the role of non-bilayer
      formation propensity. On the basis of these results it is postulated that PA
      might increase the bilayer-destabilizing effects of PE, and hence increase the
      translocation efficiency of apocyt.c and its leakage-induction ability.

PMID- 11237874
TI  - 'Shed' furin: mapping of the cleavage determinants and identification of its C
      terminus.
AB  - The human endoprotease furin is involved in the proteolytic maturation of the
      precursor molecules of a wide variety of bioactive proteins. Despite its
      localization in the membranes of the trans-Golgi system by means of a
      transmembrane domain, it has repeatedly been reported to form a C-terminally
      truncated, naturally secreted form referred to as 'shed' furin. In order to
      identify the cleavage site, internal deletion mutants of increasing size, N
      terminal to Leu(708), and subsequently individual amino acid substitutions were
      introduced, and Arg(683) was identified as the prime determinant for shedding. MS
      analysis determined Ser(682) as the C-terminus of shed furin, suggesting that
      monobasic cleavage may occur N-terminal to Arg(683). Alteration of Arg(683)
      directs the shedding mechanism to alternative cleaving sites previously unused.

PMID- 11237875
TI  - Guanylate cyclase in Dictyostelium discoideum with the topology of mammalian
      adenylate cyclase.
AB  - The core of adenylate and guanylate cyclases is formed by an intramolecular or
      intermolecular dimer of two cyclase domains arranged in an antiparallel fashion.
      Metazoan membrane-bound adenylate cyclases are composed of 12 transmembrane
      spanning regions, and two cyclase domains which function as a heterodimer and are
      activated by G-proteins. In contrast, membrane-bound guanylate cyclases have only
      one transmembrane spanning region and one cyclase domain, and are activated by
      extracellular ligands to form a homodimer. In the cellular slime mould,
      Dictyostelium discoideum, membrane-bound guanylate cyclase activity is induced
      after cAMP stimulation; a G-protein-coupled cAMP receptor and G-proteins are
      essential for this activation. We have cloned a Dictyostelium gene, DdGCA,
      encoding a protein with 12 transmembrane spanning regions and two cyclase
      domains. Sequence alignment demonstrates that the two cyclase domains are
      transposed, relative to these domains in adenylate cyclases. DdGCA expressed in
      Dictyostelium exhibits high guanylate cyclase activity and no detectable
      adenylate cyclase activity. Deletion of the gene indicates that DdGCA is not
      essential for chemotaxis or osmo-regulation. The knock-out strain still exhibits
      substantial guanylate cyclase activity, demonstrating that Dictyostelium contains
      at least one other guanylate cyclase.

PMID- 11237876
TI  - Biochemical characterization of the 2-ketoacid reductases encoded by ycdW and
      yiaE genes in Escherichia coli.
AB  - Glyoxylate is an important intermediate of the central microbial metabolism
      formed from acetate, allantoin or glycolate. Depending on the physiological
      conditions, glyoxylate is incorporated into the central metabolism by the
      combined actions of the activity of malate synthase and the D-glycerate pathway,
      or alternatively it can be reduced to glycolate by constitutive glyoxylate
      reductase activity. At present no information is available on this latter enzyme
      in Escherichia coli, although similar enzymes, classified as 2-hydroxyacid
      dehydrogenases, have been characterized in other organisms. A BLAST search using
      as the query sequence the hydroxypyruvate/glyoxylate reductase from Cucumis
      sativus identified as an orthologue the yiaE gene of E. coli encoding a
      ketoaldonate reductase. Use of this sequence in a subsequent BLAST search yielded
      the ycdW gene as a good candidate to encode glyoxylate reductase in this
      bacterium. Cloning and overexpression of the ycdW gene showed that its product
      displayed a high NADPH-linked glyoxylate reductase activity, and also catalysed
      the reduction of hydroxypyruvate with a lower efficiency. Disruption of the ycdW
      gene by a chloramphenicol acetyltransferase ('CAT') cassette did not totally
      abolish the glyoxylate reductase activity, indicating that another enzyme
      accomplished this function. The similarity with YiaE led us to test whether this
      protein was responsible for the remaining glyoxylate reductase activity.
      Purification of YcdW and YiaE proteins permitted their kinetic characterization
      and comparison. Analysis of the catalytic power (k(cat)/K(m)) disclosed a higher
      ratio of YcdW for glyoxylate and of YiaE for hydroxypyruvate.

PMID- 11237877
TI  - Increased inwardly rectifying potassium currents in HEK-293 cells expressing
      murine transient receptor potential 4.
AB  - Drosophila transient receptor potential (Trp) and its mammalian homologues are
      postulated to form capacitative Ca2+ entry or store-operated channels. Here we
      show that expression of murine Trp4 in HEK 293 cells also leads to an increase in
      inwardly rectifying K+ currents. No similar increase was found in cell lines
      expressing Trp1, Trp3 or Trp6. Consistent with typical characteristics of inward
      rectifiers, the K+ currents in Trp4-expressing cells were blocked by low
      millimolar concentrations of Cs+ and Ba2+, but not by 1.2 mM Ca2+, and were only
      slightly inhibited by 5 mM tetraethylammonium. Single channel recordings of
      excised inside-out patches revealed the presence of two conducting states of 51
      pS and 94 pS in Trp4-expressing cells. The outward current in the excised patches
      was blocked by 1 mM spermine, but not by 1 mM Mg2+. How Trp4 expression causes
      the increase in the K+ currents is not known. We propose that Trp4 either
      participates in the formation of a novel K+ channel or up-regulates the
      expression or activity of endogenous inwardly rectifying K+ channels.

PMID- 11237879
TI  - Biometric gonioscopy for measuring the anterior chamber angle.

PMID- 11237883
TI  - Interleukin-10 and intraocular-central nervous system lymphoma.

PMID- 11237884
TI  - Interleukin-10 and intraocular-central nervous system lymphoma.

PMID- 11237885
TI  - Changes in AC angle width and depth after IOL implantation in eyes with glaucoma.

PMID- 11237887
TI  - Simultaneous vs. bilateral LASIK.

PMID- 11237889
TI  - Pyramidal anterior polar cataracts.

PMID- 11237891
TI  - Management of posterior segment IOFBs.

PMID- 11237894
TI  - Removal of periocular veins by sclerotherapy.

PMID- 11237895
TI  - Are the submacular surgery trials still relevant in an era of photodynamic
      therapy?

PMID- 11237896
TI  - Lower eyelid CO(2) laser rejuvenation: a randomized, prospective clinical study.
AB  - PURPOSE: The effect of transconjunctival blepharoplasty alone compared with
      transconjunctival blepharoplasty and CO(2) laser skin resurfacing on lower lid
      bulging and wrinkles was examined. DESIGN: Randomized clinical trial.
      PARTICIPANTS: Forty-four subjects, including 13 men and 31 women. METHODS:
      Subjects were prospectively randomly assigned into two groups: (1)
      transconjunctival blepharoplasty with immediate CO(2) laser resurfacing or (2)
      transconjunctival blepharoplasty with CO(2) laser resurfacing 2 months later.
      Standardized photographs were taken before and 2 months after each procedure. A
      trained, masked observer graded the photographs. MAIN OUTCOME MEASURES: Bulging
      and wrinkles of the medial, central, and lateral portions of the lower lid were
      scored and compared at specified end points. RESULTS: Transconjunctival
      blepharoplasty alone resulted in an improvement in lower lid bulging in 92% of
      subjects, whereas lower lid wrinkling worsened in 46%. When transconjunctival
      blepharoplasty was performed with simultaneous CO(2) laser resurfacing, or with
      CO(2) laser resurfacing 2 months later, a statistically significant improvement
      in wrinkles occurred (chi square = 20.625; P < 0.0005). The timing of the
      procedures had no statistically significant effect on final outcome. No subject
      had lower lid retraction develop. CONCLUSIONS: Transconjunctival blepharoplasty
      and adjunctive CO(2) laser resurfacing represents an excellent alternative to
      transcutaneous lower blepharoplasty. The procedure addresses lower lid wrinkles,
      skin redundancy, and fat herniation without a scar and with little risk of lower
      lid retraction.

PMID- 11237897
TI  - Removal of periocular veins by sclerotherapy.
AB  - PURPOSE: Prominent periocular veins, especially of the lower eyelid, are not
      uncommon and patients often seek their removal. Sclerotherapy is a procedure that
      has been successfully used to permanently remove varicose and telangiectatic
      veins of the lower extremity and less frequently at other sites. Although it has
      been successfully used to remove dilated facial veins, it is seldom performed and
      often not recommended in the periocular region for fear of complications
      occurring in adjacent structures. The purpose of this study was to determine
      whether sclerotherapy could safely and effectively eradicate prominent periocular
      veins. DESIGN: Noncomparative case series. PARTICIPANTS: Fifty adult female
      patients with prominent periocular veins in the lower eyelid were treated
      unilaterally. PATIENTS AND METHODS: Sclerotherapy was performed with a 0.75%
      solution of sodium tetradecyl sulfate. All patients were followed for at least 12
      months after treatment. MAIN OUTCOME MEASURES: Complete clinical disappearance of
      the treated vein was the criterion for success. RESULTS: All 50 patients were
      successfully treated with uneventful resorption of their ectatic periocular
      veins. No patient required a second treatment and there was no evidence of
      treatment failure at 12 months. No new veins developed at the treated sites and
      no patient experienced any ophthalmologic or neurologic side effects or
      complications. CONCLUSIONS: Sclerotherapy appears to be a safe and effective
      means of permanently eradicating periocular veins.

PMID- 11237898
TI  - Amniotic membrane transplantation after extensive removal of primary and
      recurrent pterygia.
AB  - OBJECTIVE: To evaluate the postoperative outcome and the recurrence rate after
      extensive removal of primary and recurrent pterygia combined with amniotic
      membrane transplantation. DESIGN: A noncomparative interventional case series.
      PARTICIPANTS: Fifty-four eyes in 54 subjects with either primary (n = 33) or
      recurrent (n = 21) pterygia operated on by one surgeon (SCGT). INTERVENTION: All
      subjects were operated on for pterygia with an extensive excision of the lesion
      followed by amniotic membrane transplantation and intraoperative injection of a
      depot corticosteroid. MAIN OUTCOME MEASURES: Cumulative rates of conjunctival
      (grade 3) and corneal (grade 4) recurrence and incidence of complications.
      RESULTS: The mean follow-up was 12.8 +/- 4.3 months for primary and 14.3 +/- 4.9
      months for recurrent pterygia. The true recurrence rate (grade 4) was 3.0%, 9.5%,
      and 5.6% for primary, recurrent, and all pterygia, respectively. The cumulative
      proportion of recurrence-free eyes at 12 months was 0.90 +/- 0.06 for primary and
      0.69 +/- 0.11 for recurrent pterygia (P = 0.047, log-rank test). Removal of the
      semilunar fold was associated with longer survival times (P = 0.063) and
      decreased failure rate (P = 0.046). A similar success rate was achieved in double
      head pterygia (1 recurrence in 11 eyes). CONCLUSIONS: Amniotic membrane
      transplantation is an effective and safe procedure for pterygium surgery, with a
      relatively low recurrence rate for both primary and recurrent pterygia. It can be
      a useful alternative to conjunctival autograft when a large conjunctival defect
      has to be covered, such as in primary double-head pterygia and in large recurrent
      pterygia.

PMID- 11237899
TI  - The profile of repeated corneal transplantation.
AB  - PURPOSE: To evaluate the primary indications for corneal transplantation in
      patients with repeated keratoplasties, graft survival, the causes and risk
      factors for failure. SETTING: Tertiary referral care center. DESIGN:
      Retrospective, noncomparative case series. METHODS: Charts of all patients who
      underwent repeated corneal transplantation between 1985 and 1998 were reviewed.
      Eighty patients underwent repeated corneal transplantation, of which six
      underwent repeated corneal transplantation in both eyes, totaling 86 eyes. A
      total of 208 keratoplasties were performed in this group; 86 primary and 122
      repeated keratoplasties. The most common primary indications for corneal
      transplantation were vascularized corneal scar in 31 of the 86 eyes (36%),
      followed by pseudophakic and aphakic bullous keratopathy (PBK, ABK). Of the
      repeated transplants, 55 eyes (64%) had one repeated graft, 27 eyes (31.4%) had
      two repeated grafts, three (3.5%) had three repeated grafts, and one (1.2%) had
      four repeated transplants. MAIN OUTCOME MEASURES: Final visual outcome and
      clarity of corneal graft. RESULTS: At the end of the follow-up period, 44 of the
      86 eyes (51%) had clear grafts, but only 39.5% had good visual outcome. The mean
      survival periods of the repeated transplants decreased gradually with the number
      of regrafting procedures, from 14.3 to 8.7 months. The mean survival period was
      longer for patients with ABK, PBK, and secondary glaucoma, and shorter for
      patients who experienced graft ulcer or surface disorders. Graft failure was
      unrelated to graft size, but was associated with vascularization (P = 0.025),
      additional surgical procedures (P < 0.0001), and postoperative complications (P <
      0.0001). There was a constant tendency for decrease in visual acuity with time.
      Final visual acuity was 20/20 to 20/40 in 13 of the 86 eyes (15%), 20/80 to
      20/200 in 23 eyes (27%), and less than 20/200 in 50 eyes (58%). The most common
      complication was immune rejection, which occurred in 65 of the 208 transplants
      (31%), followed by secondary glaucoma in 48 eyes (23%) and cataract in 19 eyes
      (9%). Graft survival decreased remarkably after the third and forth regrafts, to
      25% and 0%, respectively, compared with the first and second regrafts, 37% and
      43%, respectively. CONCLUSIONS: "High-risk" preoperative conditions,
      postoperative complications, and the need for additional surgical interventions
      may decrease graft survival. Close follow-up, extended use of antiinflammatory,
      antiviral, and immunosuppressive drugs, and avoiding additional surgical
      interventions as much as possible may decrease graft failure and the need for
      repeated keratoplasties.

PMID- 11237901
TI  - Preschool vision screening: summary of a task force report.

PMID- 11237900
TI  - Antibiotic resistance pattern and visual outcome in experimentally-induced
      Staphylococcus epidermidis endophthalmitis in a rabbit model.
AB  - OBJECTIVE: To study whether the clinical outcome of Staphylococcus epidermidis
      induced endophthalmitis in rabbits is related to the antibiotic resistance
      pattern of the infecting strain. DESIGN: Experimental animal study. PARTICIPANTS:
      The right eyes of 36 New Zealand white albino rabbits were inoculated with
      strains of S. epidermidis that displayed various patterns of antibiotic
      resistance. METHODS: There were 12 rabbits in each of three study groups: fully
      antibiotic susceptible (FS), partially antibiotic resistant (PR), and
      multiresistant (MR). Five days after inoculation, the eyes were enucleated and
      prepared for histologic studies. MAIN OUTCOME MEASURES: Comparisons among the
      three groups were made based on electroretinographic (ERG) findings, histologic
      evaluation by a masked observer, and clinical examination. RESULTS:
      Electroretinographic findings on all rabbits were made by an unmasked observer.
      At 30 hours after inoculation, the ERG was diminished to 65% of normal for group
      FS, compared with a flat ERG waveform for groups PR (P < 0.05) and MR (P < 0.05).
      The ERG waveform was flat for all three groups at 72 hours after inoculation.
      Histologic evaluation by use of a histologic score revealed that the degree of
      inflammation and destruction of the retina was less for group FS (n = 10)
      compared with groups PR (n = 8) and MR (n = 8). Clinical examination revealed
      that there was a trend of less ocular inflammation for group FS compared with
      groups PR and MR. CONCLUSIONS: In a rabbit model of S. epidermidis-induced
      endophthalmitis, antibiotic-susceptible strains caused less inflammation and
      destruction of the infected retina than did antibiotic-resistant strains.

PMID- 11237902
TI  - Relationship of dissociated vertical deviation and the timing of initial surgery
      for congenital esotropia.
AB  - PURPOSE: To clarify the incidence of dissociated vertical deviation (DVD) among
      patients with congenital esotropia and to identify any relationship between the
      time when patients undergo their initial strabismus surgery and the time when
      they may subsequently have DVD develop. DESIGN: Noncomparative case series.
      PARTICIPANTS: One hundred five consecutive patients undergoing surgery for
      congenital esotropia over a 10-year period. METHODS: All patients underwent
      bimedial rectus recession before 24 months of age. MAIN OUTCOME MEASURES:
      Patients were followed postoperatively to note the age at onset of clinically
      evident DVD. RESULTS: By 6 years of age, 92% of available patients had DVD. The
      mean age at onset was 2.81 +/- 1.37 years. There was no significant difference
      between patients surgically aligned before 6 months of age compared with those
      aligned between 6 and 12 or 12 and 24 months of age. CONCLUSIONS: DVD occurs in
      almost all patients with surgically treated congenital esotropia, and its
      development is unrelated to the timing of surgical intervention during the first
      24 months of life.

PMID- 11237903
TI  - Micro syndrome in Muslim Pakistan children.
AB  - OBJECTIVE: To date, Micro syndrome has been reported in only three children from
      one family. We describe an additional 14 children from 11 families. DESIGN:
      Retrospective case series. PARTICIPANTS: Fourteen children from 11 families
      attending one of five British hospitals. MAIN OUTCOME MEASURES: The following
      features were documented: pre- and postoperative eye findings, electrophysiologic
      analysis, systemic abnormalities, development, neuroimaging, genealogy,
      geographic origin of family. RESULTS: We expand and modify the description of
      ocular and electrophysiologic findings in Micro syndrome. The eye findings of
      microphakia, microphthalmos, characteristic lens opacity, and atonic pupils were
      the presenting feature in all infants and were the most reliable diagnostic signs
      in the immediate postnatal period. Cortical visual impairment, microcephaly, and
      developmental delay were not always detectable initially; they developed in all
      children by 6 months of age. Microgenitalia were a useful diagnostic clue in
      affected males only. Therefore, eye features were more consistently useful in
      determining diagnosis than dysmorphology or brain imaging. The families of all
      the children originate from the Muslim population of Northern Pakistan.
      Inheritance is likely to be autosomal recessive. CONCLUSIONS: Micro syndrome
      usually presents to the ophthalmologist, who may be able to make the diagnosis on
      the basis of characteristic eye findings combined with ethnic origin. Initially,
      the nature and severity of nonophthalmic features are not apparent. Early
      diagnosis of the underlying condition is important to guide management of the
      cataracts, glaucoma, and developmental delay. It is helpful for the family and
      medical staff to be aware of the low level of vision that develops despite
      optimal ophthalmic intervention. Genetic counseling extending into the wider
      family is particularly important in view of the high rate of consanguinity.

PMID- 11237904
TI  - Lens opacities and mortality : the Barbados Eye Studies.
AB  - OBJECTIVE: To evaluate the association between cataract and mortality in a black
      population by type of opacity, which has not been documented previously. DESIGN:
      Population-based cohort study. PARTICIPANTS: The Barbados Incidence Study of Eye
      Diseases reexamined the Barbados Eye Study cohort, identified through a simple
      random sample of predominantly black Barbadian-born citizens, aged 40 to 84
      years. Of those eligible, 85% (3427 participants) had a 4-year follow-up visit.
      METHODS: Baseline and follow-up visits included an interview, blood pressure and
      other measurements, and a detailed ophthalmologic examination with slit-lamp lens
      gradings (Lens Opacities Classification System [LOCS] II protocol). Mortality at
      follow-up was verified from Ministry of Health records. MAIN OUTCOME MEASURES:
      Lens opacities were defined by a LOCS II score of 2 or more. Opacity types were
      classified in two ways: (1) single (cortical-only, nuclear-only, and posterior
      subcapsular-only) and mixed opacities; and (2) any cortical, any nuclear, or any
      posterior subcapsular opacities. Information on dates and causes of death was
      obtained from death certificates. RESULTS: Cardiovascular disease was the
      principal cause of death in black participants (3.6%), followed by malignant
      neoplasms (1.4%). The cumulative 4-year mortality varied with lens types,
      increasing from 3.2% for those without cataract to 6.0% for cortical-only, 8.8%
      for nuclear-only, and 20.9% for mixed opacities. Persons with mixed opacities had
      a 1.6-fold increase in mortality, while controlling for other factors (age, male
      gender, diabetes, hypertension, obesity, cigarette smoking, cardiovascular
      disease, and family history of diabetes) in Cox proportional-hazards regression
      analyses. Persons with any nuclear opacities also had increased mortality (death
      rate ratio, 1.5). The death rate ratios increased with age, but peaked at age 60
      to 69 years. Coexisting diabetes further increased mortality: people with mixed
      opacities and diabetes had a 2.7-fold increased risk of death. A trend toward
      increased mortality from neoplasms was observed for individuals with mixed
      opacities or with any nuclear opacities. CONCLUSIONS: Participants with mixed
      opacities or any nuclear opacities had increased 4-year mortality rates, with
      diabetes acting as an effect modifier. This study is the first to identify a
      relationship between type of cataract and mortality in an African-descent
      population.

PMID- 11237905
TI  - Eradication of posterior capsule opacification: documentation of a marked
      decrease in Nd:YAG laser posterior capsulotomy rates noted in an analysis of 5416
      pseudophakic human eyes obtained postmortem.
AB  - OBJECTIVE: (1) To report the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser
      posterior capsulotomy rate (%) of eight rigid and foldable intraocular lens (IOL)
      designs in a series of 5416 pseudophakic human eyes obtained postmortem,
      accessioned in our center between January 1988 and January 2000. (2) To identify
      factors that are instrumental in reducing the incidence of posterior capsule
      opacification, (PCO, secondary cataract) and hence the need for Nd:YAG laser
      posterior capsulotomy. DESIGN: Comparative autopsy tissue analysis. PARTICIPANTS:
      A total of 5416 globes with posterior chamber intraocular lens (PC-IOLs) obtained
      postmortem received from Lions Eye Banks between 1988 and 2000. METHODS: Miyake
      Apple posterior photographic technique. Special reference was given to the
      presence or absence of Nd:YAG laser posterior capsulotomy orifice on the
      posterior capsule of each eye. MAIN OUTCOME MEASURES: The Nd:YAG laser posterior
      capsulotomy rate (%) as of January 2000 was documented. In addition, the Nd:YAG
      laser posterior capsulotomy rate for each lens was plotted on a monthly basis for
      the same period, creating a computerized trend or "timeline" for each IOL style.
      RESULTS: Relatively high Nd:YAG laser posterior capsulotomy rates ranging from
      20.3% to 33.4% were noted with four relatively older designs (high incidence of
      implantation between 1988 and the early 1990s). Four modern foldable IOLs
      manufactured from silicone and acrylic materials had significantly lower Nd:YAG
      laser posterior capsulotomy rates ranging from 0.9% (Alcon Acrysof) to 17.1%. The
      difference in Nd:YAG rates among the eight IOL designs was found to be
      significant (P < 0.0001, chi-square test). Comparing foldable versus rigid
      designs, the foldable IOLs were associated with a much lower Nd:YAG laser
      posterior capsulotomy rate (14.1% vs. 31.1%). CONCLUSIONS: By use of the six
      factors regarding surgical technique and IOL choice described in this article, we
      strongly believe that the overall incidence of PCO and hence the incidence of
      Nd:YAG laser posterior capsulotomy is now rapidly decreasing from rates as high
      as 50% in the 1980s to early 1990s. Surgical tools and IOLs are now available to
      bring these rates down to single digits. Careful application and use of these
      tools by surgeons can genuinely lead in the direction of virtual eradication of
      secondary cataract, the second most common cause of visual loss worldwide.

PMID- 11237906
TI  - Synthesis of the literature on the effectiveness of regional anesthesia for
      cataract surgery.
AB  - OBJECTIVE: To synthesize the findings of the randomized trials of regional
      anesthesia management strategies for cataract surgery. DESIGN: Literature review
      and analysis. METHOD: The authors performed a systematic search of the literature
      to identify all articles pertaining to regional anesthesia during cataract
      surgery on adults. One investigator abstracted the content of each article onto a
      custom-designed form. A second investigator corroborated the findings. The
      evidence supporting the anesthesia approaches was graded by consensus as good,
      fair, poor, or insufficient. MAIN OUTCOME MEASURES: Evidence supporting the
      effectiveness of different forms of regional anesthesia. RESULTS: There was good
      evidence that retrobulbar and peribulbar blocks provide equivalent akinesia and
      pain control during cataract surgery. Additionally, sub-Tenon's blocks were at
      least as effective as retrobulbar and peribulbar blocks. There was good evidence
      that retrobulbar block provides better pain control during surgery than topical
      anesthesia, and there was fair evidence that peribulbar block provides better
      pain control than topical anesthesia. CONCLUSIONS: This synthesis of the
      literature demonstrates that currently used approaches to anesthesia management
      provide adequate pain control for successful cataract surgery, but there is some
      variation in the effectiveness of the most commonly used techniques. Data are
      needed on patient preferences to determine the optimal strategies for anesthesia
      management during cataract surgery.

PMID- 11237908
TI  - Refractive changes caused by hypoxia after laser in situ keratomileusis surgery.
AB  - OBJECTIVE: To determine whether hypoxia induces refractive changes in subjects
      who have had laser in situ keratomileusis (LASIK) refractive surgery. DESIGN:
      Prospective paired eye clinical trial. PARTICIPANTS: There were 20 LASIK subjects
      (40 eyes) and 20 myopic non-LASIK controls (40 eyes). INTERVENTION: Each subject
      had one eye exposed to ocular surface hypoxia (humidified nitrogen) by use of an
      airtight goggle system at sea level for 2 hours. The other eye was simultaneously
      exposed to humidified, compressed air (21% oxygen) with the same airtight goggle
      system. MAIN OUTCOME MEASURES: Keratometry, cycloplegic refraction, and
      pachymetry were compared before and after exposure by use of repeated measures
      analysis of variance. RESULTS: A significant myopic shift (P: < 0.01) occurred in
      LASIK corneas exposed to hypoxia compared with myopic control subjects. A
      significant increase in corneal thickening occurred symmetrically in both LASIK
      and control subjects exposed to hypoxia. There was a trend toward corneal
      steepening (keratometry) in LASIK subjects, but this was not statistically
      significant. CONCLUSIONS: These results suggest that ocular surface hypoxia
      induces a myopic shift in LASIK subjects.

PMID- 11237907
TI  - The methodologic quality of clinical trials on regional anesthesia for cataract
      surgery.
AB  - OBJECTIVE: To assess the methodologic quality of published randomized trials of
      regional anesthesia management strategies for cataract surgery. DESIGN:
      Literature review and analysis. METHOD: We performed a systematic search of the
      literature to identify all articles pertaining to regional anesthesia for
      cataract surgery on adults. Overall quality scores and scores for individual
      methodologic domains were based on the evaluations of two investigators
      experienced in methodologic research who independently reviewed all relevant
      articles using a quality abstraction form. MAIN OUTCOME MEASURES: Study quality
      in each of five domains: representativeness, bias and confounding, intervention
      description, outcomes and follow-up, and statistical quality and interpretation.
      RESULTS: Eighty-two randomized clinical trials were identified with a mean
      overall quality score of 44%. The mean domain scores ranged from 37% for
      representativeness to 58% for outcomes and follow-up. Forty percent or fewer
      studies received the maximum score for reporting the setting, the population, and
      the start and end dates; describing the inclusion and exclusion criteria;
      adequately randomizing subjects; and adequately masking individuals participating
      in the study. Key outcomes were often inadequately reported, including the
      distribution of patient-reported pain scores and the mean surgical time.
      CONCLUSIONS: Greater attention to methodologic quality and detailed reporting of
      study results will improve the ability of readers to interpret the results of
      clinical trials assessing regional anesthesia for cataract surgery.

PMID- 11237909
TI  - Phototherapeutic keratectomy for decentration and central islands after
      photorefractive keratectomy.
AB  - PURPOSE: To determine visual outcomes after treatment of decentration and central
      islands occurring after photorefractive keratectomy (PRK). DESIGN: Retrospective,
      noncomparative case series. PARTICIPANTS: Patients (n = 14) who exhibited
      decentration or central islands after PRK and photoastigmatic keratectomy (PARK).
      METHODS: Fourteen eyes with post-PRK decentration (group I) or central islands
      (group II) were treated by transepithelial phototherapeutic keratectomy guided by
      epithelial fluorescence without modulating agents, and subsequently were treated
      with PRK or PARK. Mean follow-up time was 9 months (range, 45 days-21 months).
      MAIN OUTCOME MEASURES: We analyzed pre- and postoperative keratometry, refractive
      errors, uncorrected visual acuity (UCVA), best-corrected visual acuity, and haze.
      In group I, we also measured pre- and postoperative decentration; in group II, we
      compared pre- and postoperative central island power. RESULTS: Group I showed
      improvement in centration (P = 0.003). Group II showed decreased central island
      power (P = 0.18). -LogMAR UCVA improved from 0.59 (20/80(+1)) to 0.17 (20/30) (P
      = 0.03) and from 0.74 (20/100(-1)) to 0.21 (20/30(-1)) (P = 0.01) after
      retreatment of groups I and II, respectively. CONCLUSIONS: Retreatment of
      patients having decentration and central islands after PRK results in improved
      visual outcomes.

PMID- 11237910
TI  - Sclerokeratitis: an unusual presentation of squamous cell carcinoma of the
      conjunctiva.
AB  - OBJECTIVE: To describe three cases of squamous cell carcinoma of the conjunctiva
      presenting with corneal and scleral inflammation, thinning, and perforation
      without any tumor formation. DESIGN: Three case reports. PARTICIPANTS: Three male
      subjects aged 76, 66, and 61 years. INTERVENTION: The subjects had symptoms of
      external ocular inflammation with focal corneal or scleral thinning and
      inflammation, as well as interstitial keratitis in two cases. Initial diagnosis
      of sclerokeratitis with limbal thinning was made in all three in addition to a
      pterygium in case 2. MAIN OUTCOME MEASURES: Diagnosis of the carcinoma was
      delayed for 2 to 24 months in two cases, whereas case 2 was diagnosed on excision
      of a pterygium from the involved area. RESULTS: All subjects developed
      intraocular extension after further scleral thinning and perforation without
      tumefaction. CONCLUSIONS: Squamous cell carcinoma of the conjunctiva may be seen
      without a distinct mass and can masquerade as sclerokeratitis, scleromalacia, or
      interstitial keratitis. It seems that diffuse growth with inflammation leads to
      thinning, necrosis, and perforation of the ocular wall with resultant intraocular
      spread. Squamous cell carcinoma should be considered in the differential
      diagnosis of corneal and scleral thinning, perforation, and inflammation of
      unknown cause, especially in the older male subject.

PMID- 11237911
TI  - Local chemotherapy with interferon-alpha for conjunctival mucosa-associated
      lymphoid tissue lymphoma: a preliminary report.
AB  - OBJECTIVE: To evaluate the efficacy of subconjunctival interferon-alpha for the
      treatment of conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma.
      DESIGN: Small, noncomparative, interventional case series. PARTICIPANTS: Five
      patients with histologically proven conjunctival MALT lymphoma were studied
      prospectively. METHODS: Patients were given 1,500,000 international units (IU) of
      interferon-alpha (IFN-alpha) (Roferon-A) subconjunctivally inside the lesion,
      three times a week for four weeks. If there was even a minimal response, a
      further cycle of 1,000,000 IU three times a week for four weeks was administered.
      Patients received a maintenance dose of 1 million IU, every 15 days for 4 times,
      after clinical resolution of the lesion. MAIN OUTCOME MEASURES: Patients were
      followed clinically, with slit lamp examination, for evidence of tumor
      disappearance or recurrence. RESULTS: Complete response was obtained in all
      patients. The lesion resolved completely by the eighth week. Four patients did
      not show any local recurrence with a median follow-up of 21 months (12-36
      months). One patient presented with a recurrence after 11 months, in association
      with systemic lymphoma progression. CONCLUSIONS: Local chemotherapy with IFN
      alpha seems to be an effective treatment modality, alternative to radiotherapy,
      for conjunctival MALT lymphomas.

PMID- 11237912
TI  - Patterns of adherence to diabetes vision care guidelines: baseline findings from
      the Diabetic Retinopathy Awareness Program.
AB  - OBJECTIVES: (1) To describe baseline patterns of adherence to American Diabetes
      Association and American Academy of Ophthalmology vision care guidelines for
      diabetes in the Diabetic Retinopathy Awareness Program, and (2) to evaluate
      factors associated with nonadherence. This paper describes the baseline
      characteristics of a population enrolled in a prospective, randomized clinical
      trial. DESIGN: Cross-sectional study. PARTICIPANTS: Between October 1993 and May
      1994, the study identified 2308 persons with diabetes, 18 years of age or older,
      who were residents of Suffolk County, New York, via a multimedia community-wide
      recruitment campaign. INTERVENTION AND METHODS: Eligibility for the trial was
      determined during a 20-minute phone interview, which included questions about
      vision care practices; diabetes management; and knowledge, attitudes, and beliefs
      about diabetes, vision, and diabetic retinopathy. This paper describes these
      patient characteristics at baseline. Eligible patients would be randomized
      subsequently to a 2-year diabetes educational intervention arm, which included
      mailed packets and newsletters focused on vision care, or to a control
      nonintervention arm. MAIN OUTCOME MEASURE: Nonadherence to guidelines at baseline
      was defined as the absence of a dilated eye examination during the year before
      recruitment into the study. RESULTS: Of the 2308 persons interviewed, 813 (35%)
      did not follow the vision care guidelines; two thirds of this group reported no
      eye examination in the year before the interview, and one third had an undilated
      examination. Ophthalmologists performed 49% of the examinations in the
      nonadherent group, versus 86% in the adherent group. In logistic regression
      analyses, factors related to nonadherence were: younger age (odds ratio [OR] =
      0.97), type 2 diabetes with or without insulin use (OR = 1.62 and 1.99,
      respectively), shorter diabetes duration (OR = 0.97), last eye examination
      performed by an optometrist (OR = 5.32) or other nonophthalmologist (OR = 4.29),
      less practical knowledge about diabetes (OR = 1.57), and no prior formal diabetes
      education (OR = 1.30). CONCLUSIONS: Within this population, more than one third
      of participants had not been following vision care guidelines. Nonadherence was
      linked to several potentially modifiable factors; changes in these factors could
      enhance the early detection of diabetic retinopathy.

PMID- 11237914
TI  - Tear function and ocular surface changes in noninsulin-dependent diabetes
      mellitus.
AB  - PURPOSE: To describe the ocular surface disorder in patients with diabetes.
      DESIGN: A prospective, case-controlled study. PARTICIPANTS: Eighty-eight eyes of
      50 noninsulin-dependent diabetes mellitus patients seen at the Department of
      Ophthalmology, Kobe University School of Medicine, from September 1998 through
      February 1999, and 40 eyes of 20 healthy control individuals were studied.
      INTERVENTION: All subjects underwent routine ophthalmic examinations, corneal
      sensitivity measurements, Schirmer test, tear film break-up time (BUT) analysis,
      and conjunctival impression cytologic analysis. MAIN OUTCOME MEASURES: Patients
      and control subjects were compared for corneal sensitivity, tear function
      parameters, goblet cell density, and squamous metaplasia grade. The relation of
      diabetic peripheral neuropathy, metabolic control, duration of disease, and
      status of retinopathy to the ocular surface disorder was also noted. RESULTS: The
      mean corneal sensitivity was significantly lower in diabetic patients, diabetic
      patients with peripheral neuropathy, and poorly controlled diabetes compared with
      control subjects (P < 0.001). The BUT and Schirmer test values were also
      significantly lower in the diabetic group, in patients with peripheral neuropathy
      and poor metabolic control. Impression cytologic analysis showed goblet cell loss
      and conjunctival squamous metaplasia, both of which again related to peripheral
      neuropathy, poor diabetic control, and decreased corneal sensitivity. The
      examined parameters did not relate to duration of disease or status of diabetic
      retinopathy. CONCLUSIONS: The ocular surface disease in diabetes is characterized
      by a disorder of tear quantity and quality, squamous metaplasia, and goblet cell
      loss, all of which seem to evolve in close proximity to the status of metabolic
      control and peripheral neuropathy.

PMID- 11237913
TI  - Stereo nonmydriatic digital-video color retinal imaging compared with Early
      Treatment Diabetic Retinopathy Study seven standard field 35-mm stereo color
      photos for determining level of diabetic retinopathy.
AB  - OBJECTIVE: To evaluate the ability to determine clinical levels of diabetic
      retinopathy, timing of next appropriate retinal evaluation, and necessity of
      referral to ophthalmology specialists using stereoscopic nonmydriatic digital
      video color retinal images as compared with Early Treatment Diabetic Retinopathy
      Study (ETDRS) seven standard field 35-mm stereoscopic color fundus photographs.
      DESIGN: Prospective, clinic-based, comparative instrument validation study.
      PARTICIPANTS: Fifty-four patients (108 eyes) with type 1 or type 2 diabetes
      mellitus selected after chart review from a single center to include the full
      spectrum of diabetic retinopathy. METHODS: Nonsimultaneous 45 degrees -field
      stereoscopic digital-video color images (JVN images) were obtained from three
      fields with the Joslin Vision Network (JVN) system before pupil dilation.
      Following pupil dilation, ETDRS seven standard field 35-mm stereoscopic color 30
      degrees fundus photographs (ETDRS photos) were obtained. Joslin Vision Network
      images and ETDRS photos were graded on a lesion-by-lesion basis by two
      independent, masked readers to assess ETDRS clinical level of diabetic
      retinopathy. An independent ophthalmology retina specialist adjudicated
      interreader disagreements in a masked fashion. MAIN OUTCOME MEASURES:
      Determination of ETDRS clinical level of diabetic retinopathy, timing of next
      ophthalmic evaluation of diabetic retinopathy, and need for prompt referral to
      ophthalmology specialist. RESULTS: There was substantial agreement (kappa = 0.65)
      between the clinical level of diabetic retinopathy assessed from the undilated
      JVN images and the dilated ETDRS photos. Agreement was excellent (kappa = 0.87)
      for suggested referral to ophthalmology specialists for eye examinations.
      Comparison of individual lesions between the JVN images and the ETDRS photos and
      for interreader comparisons were comparable to the prior ETDRS study.
      CONCLUSIONS: Undilated digital-video images using the JVN system were comparable
      photographs for the determination of diabetic retinopathy level. The results
      validate the agreement between nonmydriatic JVN images and dilated ETDRS
      photographs and suggest that this digital technique may be an effective
      telemedicine tool for remotely determining the level of diabetic retinopathy,
      suggesting timing of next retinal evaluation and identifying the need for prompt
      referral to ophthalmology specialists. Thus, the JVN system would be an
      appropriate tool for facilitating increased access of diabetic patients into
      recommended eye evaluations, but should not be construed as a paradigm that would
      replace the need for comprehensive eye examinations.

PMID- 11237915
TI  - The prevalence of cupping in end-stage arteritic and nonarteritic anterior
      ischemic optic neuropathy.
AB  - OBJECTIVE: To evaluate the prevalence of cupping in arteritic anterior ischemic
      optic neuropathy (AAION) and nonarteritic anterior ischemic optic neuropathy
      (NAION). DESIGN: Retrospective, observational case series. PARTICIPANTS: Three
      hundred one patients. METHODS: Review of clinical records and color fundus
      photographs. MAIN OUTCOME MEASURES: Photographic and clinical interpretation of
      optic nerve appearance. RESULTS: Ninety-two patients with AAION and 102 with
      NAION were included in the study. Disc photographs of 42 patients (48%) with
      AAION and 32 patients (31%) with NAION were available for reassessment. These
      were presented in a masked fashion along with a random sample of 27 disc pairs
      considered to be 'normal' and 27 disc pairs with 'established glaucoma' according
      to two examiners. Cupping was present in 92% of eyes with AAION secondary to
      giant cell arteritis and in 2% of eyes with NAION (kappa = 0.96; P < 0.001).
      CONCLUSIONS: The end-stage optic disc appearance in AAION secondary to giant cell
      arteritis is cupping, whereas segmental or diffuse pallor without cupping is the
      typical disc appearance after NAION.

PMID- 11237916
TI  - Relationship between Helicobacter pylori infection and glaucoma.
AB  - OBJECTIVE: To determine the frequency of Helicobacter pylori (H. pylori)
      infection in glaucoma patients and in anemic control participants. DESIGN:
      Prospective, nonrandomized, comparative study. PARTICIPANTS: The authors
      investigated 32 patients with chronic open-angle glaucoma (COAG), 9 patients with
      pseudoexfoliation glaucoma (PEG), and 30 age-matched anemic control participants.
      METHODS: Upper gastrointestinal endoscopy was performed to evaluate macroscopic
      abnormalities, and gastric mucosal biopsy specimens were obtained for the
      presence of H. pylori infection tested by rapid urease slide test (CLO test) and
      by Cresyl fast violet staining, Giemsa staining, or both. The presence of
      gastritis was classified in accordance with the Sydney system by using
      hematoxylin and eosin stain. In addition, intestinal metaplasia was evaluated
      with Alcian blue stain. Saliva samples were also tested by CLO. Serum was
      analyzed for the presence of H. pylori-specific IgG antibodies by enzyme-linked
      immunosorbent assay. MAIN OUTCOME MEASURE: Histologic examination for the
      presence of H. pylori. RESULTS: In 87.5% of the COAG patients, 88.9% of the PEG
      patients, and 46.7% of the anemic control participants, H. pylori infection was
      histologically confirmed (odds ratio, 8.00; chi-square, 11.81; P = 0.0006 and
      9.14; chi-square, 5.01; P = 0.02, respectively). H. pylori was detected by urease
      test: (1) in the gastric mucosa in 71.9% of the COAG patients, in 77.8% of the
      PEG patients, and in 46.7% of the anemic control participants (P = 0.03 and P >
      0.05, respectively); and (2) in the saliva in 37.5% of the COAG patients, in
      55.6% of the PEG patients, and in 30% of the anemic control participants (P >
      0.05). Sixty-eight percent of glaucoma patients and 30% of anemic control
      participants were seropositive for H. pylori (P = 0.002). When compared with
      anemic control participants, glaucoma patients exhibited less often endoscopic
      normal appearance of gastric mucosa (P = 0.01), and more often antral gastritis
      (P = 0.0004) or peptic ulcer disease (P = 0.01). Histologic grade 3 gastritis was
      observed only in the glaucoma patients (P = 0.03). CONCLUSIONS: H. pylori
      infection seems more frequent in glaucoma patients. If confirmed, this may
      indicate either a common factor that causes susceptibilities to both glaucoma and
      H. pylori infection or that H. pylori may be a causal factor for developing
      glaucoma.

PMID- 11237917
TI  - Otago glaucoma surgery outcome study : long-term results of uveitis with
      secondary glaucoma drained by Molteno implants.
AB  - OBJECTIVE: This study was undertaken in Otago, New Zealand, to provide data on
      the long-term results of cases of uveitis with secondary glaucoma drained by
      Molteno implants. DESIGN: A prospective, noncomparative case series of all cases
      of chronic uveitis with secondary glaucoma drained by Molteno implants from 1978
      through 1998. PARTICIPANTS: Forty eyes of 35 patients. INTERVENTION: Insertion of
      Molteno implant. MAIN OUTCOME MEASURES: Intraocular pressure, visual acuity, and
      progressive visual field loss. RESULTS: Insertion of a Molteno implant was
      effective in controlling the intraocular pressure at 21 mmHg or less with a
      probability of 0.87 (95% confidence interval [CI], 0.76, 0.98) and 0.77 (95% CI,
      0.60, 0.93) at 5 and 10 or more years after surgery. The mean visual acuity
      improved from 20/100 to 20/70 immediately after operation. This value declined to
      20/130 at 5 and 10 years after surgery and then improved slightly to 20/120 at 15
      years after surgery. In these eyes, the Kaplan-Meier estimated probability of
      retaining useful vision (visual acuity >20/400; visual field >5 degrees radius)
      was 0.75 (95% CI, 0.61, 0.89) and 0.71 (95% CI, 0.55, 0.87) at 5 and 7 or more
      years after surgery. CONCLUSIONS: The insertion of a Molteno implant controlled
      the intraocular pressure in 76% of cases over the follow-up period. Patients in
      whom the uveitis was well controlled maintained their visual acuity and visual
      fields, whereas the proportion of cases requiring steroids and the doses required
      fell progressively over the period of follow-up. Failures were related to
      complications of advanced disease, previous intraocular surgery, and failure to
      control the uveitis. The drainage system provided by the Molteno implant proved
      robust, continuing to function well despite continuous activity of the uveitis,
      acute exacerbations of the uveitis, and all subsequent intraocular surgery
      including cataract extraction, keratoplasty, and vitrectomy.

PMID- 11237918
TI  - Clinical evaluation and risk factors of time to failure of Ahmed Glaucoma Valve
      implant in pediatric patients.
AB  - PURPOSE: To evaluate the clinical results and the risk factors related to time to
      failure of the Ahmed Glaucoma Valve implant (New World Medical, Inc., Rancho
      Cucamonga, CA), an aqueous shunting device with a unidirectional valve mechanism,
      in pediatric patients. DESIGN: Retrospective, noncomparative, interventional case
      series. PARTICIPANTS: We studied 35 Ahmed Glaucoma Valve implants in 35 eyes of
      29 patients less than 15 years of age (median, 2.4 years; range, 0-14.8 years).
      METHODS: Thirty-five Ahmed Glaucoma Valve implants were placed in eyes of
      pediatric patients with refractory glaucoma between December 1994 and March 1999.
      MAIN OUTCOME MEASURES: Time after surgery without failure, intraocular pressure
      reduction, risk factors related to time to failure, and postoperative
      complications were evaluated. RESULTS: The cumulative probabilities of success
      according to Kaplan-Meier analysis 12 and 24 months after implantation were 70.1%
      +/- 8.5% and 63.7% +/- 9.9%, respectively. Intraocular pressure was reduced from
      a preoperative mean of 28.8 +/- 4.5 mmHg to 18.1 +/- 2.4 mmHg by postoperative
      month 18. Shallow anterior chambers of different grades developed in nine eyes
      (25.7%) on the first postoperative day; this was associated with choroidal
      detachment in four eyes. Nine eyes (25.7%) experienced malposition, causing
      failure in six eyes. In three other eyes (8.5%), the average intraocular pressure
      at the last two follow-up examinations was more than 22 mmHg. Congenital glaucoma
      and surgical experience were significantly associated with time to failure.
      CONCLUSIONS: The 12- and 24-month success rates of the Ahmed Glaucoma Valve
      implant in our study confirm its viability in the management of refractory
      infantile glaucoma. The complications related to overfiltration during the
      immediate postoperative period appear to be less severe than those associated
      with other drainage devices and resolve spontaneously. Diagnosis, number of
      previous glaucoma procedures, and the surgeon's experience seem to be related to
      the survival of the Ahmed Glaucoma Valve implant.

PMID- 11237919
TI  - Intermediate-term outcomes of 350-mm(2) Baerveldt glaucoma implants.
AB  - OBJECTIVE: To determine the intermediate-term outcome of 350-mm(2) Baerveldt
      glaucoma implants. DESIGN: Retrospective, noncomparative case series.
      PARTICIPANTS: Sixty-five patients (65 eyes). INTERVENTION: Implantation of 350
      mm(2) Baerveldt glaucoma drainage device. MAIN OUTCOME MEASURES: Intraocular
      pressure, number of glaucoma medications, best-corrected Snellen visual acuity,
      length of follow-up, risk factors for failure, and complications. RESULTS: Mean
      intraocular pressure was reduced from a preoperative value of 32 mmHg to a 2-year
      postoperative value of 14 mmHg (56% reduction, P < 0.001). Success rates at 2
      year follow-up were 71%, 81%, 78%, 60%, and 47% for the overall group, primary
      open-angle glaucoma group, neovascular group, uveitic group, and other group,
      respectively. After accounting for the effect of diagnosis group, significant
      risk factors in the overall group for failure at 2 years included younger age,
      high preoperative intraocular pressure, and more prior incisional surgeries.
      Glaucoma medication use in our overall study population was reduced from 2.5 mean
      preoperative medications to 0.8 postoperative medications (68%). Median change in
      Snellen visual acuity between preoperative and 2-year postoperative visits was
      not significant in the overall group. Postoperative complications included
      choroidal effusion in 15 patients (23%), tube obstruction by blood or vitreous in
      five patients (8%), phthisis in four patients (6%), aqueous misdirection in two
      patients (3%), strabismus in two patients (3%), tube-cornea touch in two patients
      (3%), endophthalmitis in two patients (3%), and retinal detachment in two
      patients (3%). No patients had suprachoroidal hemorrhage. CONCLUSIONS: The 350
      mm(2) Baerveldt glaucoma implants are a safe and effective treatment for
      intermediate-term intraocular pressure control in patients with refractory
      glaucoma.

PMID- 11237920
TI  - Optic nerve head circulation after intraocular pressure reduction achieved by
      trabeculectomy.
AB  - OBJECTIVE: To study the effects of trabeculectomy and needling revision of poorly
      functioning blebs on the optic nerve head (ONH) circulation in patients with
      primary open-angle glaucoma (POAG). DESIGN: Prospective, nonrandomized, self
      controlled trial. PARTICIPANTS: Nineteen POAG patients (age range, 52 +/- 12
      years; mean +/- standard deviation) undergoing trabeculectomy and six POAG
      patients (age range, 62 +/- 14 years) undergoing needling revision of the bleb.
      METHODS: Using the laser speckle method, the normalized blur (NB) value, a
      quantitative index of blood velocity, was determined every 0.125 seconds and
      averaged more than three cardiac pulses in the optic nerve head (NB(ONH)). MAIN
      OUTCOME MEASURES: The NB(ONH) and intraocular pressure (IOP) in both eyes, and
      blood pressure (BP) and pulse rate (PR) were measured before and 2 days and 1, 4,
      and 8 weeks after trabeculectomy, and also before and 10 and 40 min after
      needling procedures. RESULTS: Intraocular pressure in the operated eye was
      significantly decreased after trabeculectomy or needling procedures, and the
      ocular perfusion pressure was significantly increased by a maximum of 38%. The
      IOP in the unoperated eye, BP, and PR did not significantly change. The NB(ONH)
      did not significantly change in either the operated or unoperated eye.
      CONCLUSIONS: Trabeculectomy and needling procedures induced little change in the
      ONH circulation.

PMID- 11237921
TI  - Population determinants of homocysteine.

PMID- 11237922
TI  - Lifestyle effects on homocysteine and an alcohol paradox.

PMID- 11237923
TI  - Iron status of free-living elderly individuals.

PMID- 11237924
TI  - Lessons for search strategies from a systematic review, in The Cochrane Library,
      of nutritional supplementation trials in patients after hip fracture.
AB  - BACKGROUND: A key aim when conducting systematic reviews of randomized controlled
      trials (RCTs) is to include all of the evidence, if possible. Serious bias may
      result if trials are missed through inadequate search strategies. OBJECTIVE: The
      objective was to evaluate the search plan for identifying RCTs in nutrition as
      part of a systematic review, in The Cochrane Library, of nutritional
      supplementation trials in patients after hip fracture. DESIGN: We identified
      potential studies by searching the electronic databases BIOSIS, CABNAR, CINAHL,
      EMBASE, HEALTHSTAR, and MEDLINE; reference lists in trial reports; and other
      relevant articles. We also contacted investigators and other experts for
      information and searched 4 nutrition journals by hand. RESULTS: We identified 15
      RCTs that met the predefined inclusion criteria. The search plan identified 8
      trials each in EMBASE, HEALTHSTAR, and MEDLINE and 7 in BIOSIS and CABNAR. BIOSIS
      was the only electronic database source of 2 trials. Eleven trials were
      identified by searching electronic databases and 2 unpublished trials were
      identified via experts in the field. We found one trial, published only as a
      conference abstract, by searching nutrition journals by hand. After publication
      of the protocol for the review in The Cochrane Library, we were informed of
      another unpublished trial. CONCLUSIONS: We found that a limited search plan based
      on only MEDLINE or one of the other commonly available databases would have
      failed to locate nearly one-half of the studies. To protect against bias, the
      search plan for a systematic review of nutritional interventions should be
      comprehensive.

PMID- 11237925
TI  - The importance of clinical research: the role of thermogenesis in human obesity.
AB  - The hypothesis that human obesity is caused by deficient thermogenesis has been
      proposed by many investigators throughout the 20th century. Supporting evidence
      was obtained from epidemiologic studies of dietary intake, animal models with
      aberrant brown adipose tissue (BAT) function, and genetic studies of human
      polymorphisms of genes involved in BAT function. Supporting evidence was also
      obtained from clinical studies of the thermogenic effect of meals, but these
      measures capture only a short portion of the day and may miss some of the
      thermogenic effect. To capture the effects throughout the day and to move the
      studies out of the metabolic ward, investigators have used the doubly labeled
      water (DLW) method to measure total daily energy expenditure. DLW studies have
      not supported the above hypothesis. Increases in total energy expenditure (TEE)
      during overfeeding have been small (0.9 +/- 0.8 MJ/d) and account for an average
      of only 18 +/- 18% of the excess energy intake. Most of this increase is in the
      resting metabolic rate. Moreover, these studies showed little variation in the
      changes in resting metabolic rate or in thermogenesis from meals during
      overfeeding. Instead, the component that is most variable and that accounts for
      the variability in weight gain during overfeeding is the energy expended in
      physical activity. This component of TEE deserves greater attention in future
      studies. These studies of thermogenesis have shown the importance of clinical
      research as part of a comprehensive approach to understanding the etiology of
      human obesity.

PMID- 11237926
TI  - Whole-body and adipose tissue glucose metabolism in response to short-term
      fasting in lean and obese women.
AB  - BACKGROUND: Alterations in glucose metabolism during early fasting may be an
      important trigger of the hormonal and metabolic responses to fasting. OBJECTIVE:
      The purpose of this study was to determine whether glucose metabolism in response
      to brief starvation differs in lean and abdominally obese women. DESIGN: We
      evaluated whole-body glucose metabolism by use of stable-isotope tracer methods
      and glucose uptake in subcutaneous abdominal adipose tissue by use of
      arteriovenous balance in 7 lean [58 +/- 2 kg; body mass index (BMI; in kg/m(2)):
      21 +/- 5] and 6 abdominally obese (96 +/- 2 kg; BMI: 36 +/- 1) women after 14 and
      22 h of fasting. RESULTS: Between 14 and 22 h of fasting, whole-body glucose
      production and disposal declined in both groups (P < 0.05), but the reduction was
      50% greater in lean than in obese women (P < 0.05). The decline in glucose uptake
      at 22 h of fasting was also lower in obese (0.11 +/- 0.04 micromol*100 g(-1) x
      min(-1)) than in lean (0.26 +/- 0.03 micromol x 100 g(-1) x min(-1)) women (P <
      0.05). Decreases in plasma insulin and leptin concentrations between 14 and 22 h
      of fasting were also lower in obese than in lean women (insulin: 20 +/- 3% and 32
      +/- 5%; leptin: 18 +/- 3% and 37 +/- 6%; both P < 0.05). CONCLUSIONS: The normal
      decline in glucose production and uptake that occurs during early fasting is
      blunted in women with abdominal obesity. These alterations in glucose metabolism
      are associated with a blunted decline in circulating concentrations of both
      insulin and leptin, which may explain some of the differences in the metabolic
      response to fasting observed between lean and abdominally obese persons.

PMID- 11237927
TI  - Short-term effects of weight loss with or without low-intensity exercise training
      on fat metabolism in obese men.
AB  - BACKGROUND: Energy restriction is known to induce a decline in fat oxidation
      during the postdiet period. Reduced fat oxidation may contribute to weight
      regain. OBJECTIVE: The present study investigated the effect of the addition of
      low-intensity exercise training to energy restriction on postdiet fat oxidation
      and on the contribution of the sympathetic nervous system to fat oxidation.
      DESIGN: Forty obese men were divided randomly into 2 groups: diet (D) and diet
      plus exercise (DE). Both groups followed an energy restriction program for 10 wk.
      Subjects in the DE group also participated in a low-intensity exercise training
      program [40% maximal oxygen uptake (VO2max)] for 12 wk. Before the intervention
      and after 12 wk, with subjects at stable body weights, we measured body
      composition, VO2max, and substrate oxidation at rest, during exercise at 50%
      VO2max, and during recovery. Measurements were made with and without
      administration of the beta-adrenergic antagonist propranolol. RESULTS: Both
      interventions led to significant decreases in body weight, fat mass, and fat-free
      mass (P < 0.001); these decreases did not differ significantly between the D and
      DE groups. Neither intervention significantly affected VO2max. The effect of the
      intervention on the respiratory exchange ratio differed significantly between the
      D and DE groups [two-way analysis of variance (ANOVA), P < 0.05]. The effect on
      the beta-adrenergic-mediated respiratory exchange ratio tended to be different
      between the 2 groups (two-way ANOVA, P = 0.09). CONCLUSION: Addition of low
      intensity exercise training to energy restriction counteracts the decline in fat
      oxidation during the postdiet period.

PMID- 11237928
TI  - Consumption of high doses of chlorogenic acid, present in coffee, or of black tea
      increases plasma total homocysteine concentrations in humans.
AB  - BACKGROUND: In population studies, high intakes of coffee are associated with
      raised concentrations of plasma homocysteine, a predictor of risk of
      cardiovascular disease. Chlorogenic acid is a major polyphenol in coffee; coffee
      drinkers consume up to 1 g chlorogenic acid/d. OBJECTIVE: We studied whether
      chlorogenic acid affects plasma total homocysteine concentrations in humans. For
      comparison we also studied the effects of black tea rich in polyphenols and of
      quercetin-3-rutinoside, a major flavonol in tea and apples. DESIGN: In this
      crossover study, 20 healthy men and women ingested 2 g (5.5 mmol) chlorogenic
      acid, 4 g black tea solids containing approximately 4.3 mmol polyphenols and
      comparable to approximately 2 L strong black tea, 440 mg (0.7 mmol) quercetin-3
      rutinoside, or a placebo daily. Each subject received each of the 4 treatments
      for 7 d, in random order. RESULTS: Total homocysteine in plasma collected 4-5 h
      after supplement intake was 12% (1.2 micromol/L; 95% CI: 0.6, 1.7) higher after
      chlorogenic acid and 11% (1.1 micromol/L; 95% CI: 0.6, 1.5) higher after black
      tea than after placebo. Total homocysteine in fasting plasma collected 20 h after
      supplement intake was 4% (0.4 micromol/L; 95% CI: 0.0, 0.8) higher after
      chlorogenic acid and 5% (0.5 micromol/L; 95% CI: 0.0, 0.9) higher after black tea
      than after placebo. Quercetin-3-rutinoside did not significantly affect
      homocysteine concentrations. CONCLUSIONS: Chlorogenic acid, a compound in coffee,
      and black tea raise total homocysteine concentrations in plasma. Chlorogenic acid
      could be partly responsible for the higher homocysteine concentrations observed
      in coffee drinkers. Whether these effects on homocysteine influence
      cardiovascular disease risk remains to be established.

PMID- 11237929
TI  - Dietary supplementation with eicosapentaenoic acid, but not with other long-chain
      n-3 or n-6 polyunsaturated fatty acids, decreases natural killer cell activity in
      healthy subjects aged >55 y.
AB  - BACKGROUND: Animal studies showed that dietary flaxseed oil [rich in the n-3
      polyunsaturated fatty acid alpha-linolenic acid (ALA)], evening primrose oil
      [rich in the n-6 polyunsaturated fatty acid gamma-linolenic acid (GLA)], and fish
      oil [rich in the long-chain n-3 polyunsaturated fatty acids eicosapentaenoic acid
      (EPA) and docosahexaenoic acid (DHA)] can decrease natural killer (NK) cell
      activity. There have been no studies of the effect on NK cell activity of adding
      these oils to the diet of humans. OBJECTIVE: Our objective was to determine the
      effect of dietary supplementation with oil blends rich in ALA, GLA, arachidonic
      acid (AA), DHA, or EPA plus DHA (fish oil) on the NK cell activity of human
      peripheral blood mononuclear cells. DESIGN: A randomized, placebo-controlled,
      double-blind, parallel study was conducted. Healthy subjects aged 55-75 y
      consumed 9 capsules/d for 12 wk; the capsules contained placebo oil (an 80:20 mix
      of palm and sunflower seed oils) or blends of placebo oil and oils rich in ALA,
      GLA, AA, DHA, or EPA plus DHA. Subjects in these groups consumed 2 g ALA, 770 mg
      GLA, 680 mg AA, 720 mg DHA, or 1 g EPA plus DHA (720 mg EPA + 280 mg DHA) daily,
      respectively. Total fat intake from the capsules was 4 g/d. RESULTS: The fatty
      acid composition of plasma phospholipids changed significantly in the GLA, AA,
      DHA, and fish oil groups. NK cell activity was not significantly affected by the
      placebo, ALA, GLA, AA, or DHA treatment. Fish oil caused a significant reduction
      (mean decline: 48%) in NK cell activity that was fully reversed by 4 wk after
      supplementation had ceased. CONCLUSION: A moderate amount of EPA but not of other
      n-6 or n-3 polyunsaturated fatty acids can decrease NK cell activity in healthy
      subjects.

PMID- 11237930
TI  - Use of a triaxial accelerometer to validate reported food intakes.
AB  - BACKGROUND: An easy and cheap method for validating reported energy intake (EI)
      is needed. OBJECTIVE: Reported EI was compared with calculated energy expenditure
      (EE(calc)) and with energy expenditure measured by the doubly labeled water
      method (EE(DLW)). DESIGN: EE was calculated on the basis of basal metabolic rate
      (BMR) measured with the ventilated-hood technique and physical activity (PA)
      measured with a triaxial accelerometer (EE(VH+PA)) and on the basis of BMR
      estimated by using World Health Organization equations and PA (EE(WHO+PA)):
      EE(calc) = -1.259 + 1.55 x BMR + 0.076 x counts/min (r(2) = 0.90, P = 0.0001).
      Subjects [n = 12 men and 12 women aged 60 +/- 3 y; body mass index (in kg/m(2)):
      26 +/- 4] reported their food intakes for 7 d and EE(DLW), EE(VH+PA), and
      EE(WHO+PA) were assessed over the same 7 d. RESULTS: Reported EI (9.0 +/- 2.1
      MJ/d) was lower (P: < 0.0001) than were EE(DLW) (11.3 +/- 2.3 MJ/d), EE(VH+PA)
      (10.8 +/- 1.7 MJ/d), and EE(WHO+PA) (10.8 +/- 1.8 MJ/d). Underreporting was 19.4
      +/- 14.0%, 16.7 +/- 13.6%, and 16.4 +/- 15.5% on the basis of EE(DLW), EE(VH+PA),
      and EE(WHO+PA), respectively. The difference of 2.7 +/- 8.0% between EE(DLW) and
      EE(VH+PA) was not related to the average of both percentages and was not
      significantly different from zero. The percentage of underreporting calculated
      with EE(WHO+PA) was not significantly different from that calculated with
      EE(DLW). CONCLUSIONS: The use of a combination of BMR (measured or estimated) and
      PA is a good method for validating reported EI. There was no significant
      difference between the percentage of underreporting calculated with EE(VH+PA),
      EE(WHO+PA), or EE(DLW).

PMID- 11237931
TI  - Dietary fat content alters insulin-mediated glucose metabolism in healthy men.
AB  - BACKGROUND: A high dietary fat intake is involved in the pathogenesis of insulin
      resistance. OBJECTIVE: The aim was to compare the effect of different amounts of
      dietary fat on hepatic and peripheral insulin sensitivity. DESIGN: Six healthy
      men were studied on 3 occasions after consuming for 11 d diets with identical
      energy and protein contents but different percentages of energy as fat and
      carbohydrate as follows: 0% and 85% [low-fat, high-carbohydrate (LFHC) diet], 41%
      and 44% [intermediate-fat, intermediate-carbohydrate (IFIC) diet], and 83% and 2%
      [high-fat, low-carbohydrate (HFLC) diet]. Insulin sensitivity was quantified by
      using a hyperinsulinemic euglycemic clamp (plasma insulin concentration:
      approximately 190 pmol/L). RESULTS: During hyperinsulinemia, endogenous glucose
      production was higher after the HFLC diet (2.5 +/- 0.3 micromol x kg(-1) x min(
      1); P < 0.05) than after the IFIC and LFHC diets (1.7 +/- 0.3 and 1.2 +/- 0.4
      micromol x kg(-1) x min(-1), respectively). The ratio of dietary fat to
      carbohydrate had no unequivocal effects on insulin-stimulated glucose uptake. In
      contrast, insulin-stimulated, nonoxidative glucose disposal tended to increase in
      relation to an increase in the ratio of fat to carbohydrate, from 14.8 +/- 5.1 to
      20.6 +/- 1.9 to 26.2 +/- 2.9 micromol x kg(-1) x min(-1) (P < 0.074 between the 3
      diets). Insulin-stimulated glucose oxidation was significantly lower after the
      HFLC diet than after the IFIC and LFHC diets: 1.7 +/- 0.8 compared with 13.4 +/-
      2.1 and 19.0 +/- 2.1 micromol x kg(-1) x min(-1), respectively (P < 0.05). During
      the clamp study, plasma fatty acid concentrations were higher after the HFLC diet
      than after the IFIC and LFHC diets: 0.22 +/- 0.02 compared with 0.07 +/- 0.01 and
      0.05 +/- 0.01 mmol/L, respectively (P < 0.05). CONCLUSION: A high-fat, low
      carbohydrate intake reduces the ability of insulin to suppress endogenous glucose
      production and alters the relation between oxidative and nonoxidative glucose
      disposal in a way that favors storage of glucose.

PMID- 11237932
TI  - Dietary glycemic load assessed by food-frequency questionnaire in relation to
      plasma high-density-lipoprotein cholesterol and fasting plasma triacylglycerols
      in postmenopausal women.
AB  - BACKGROUND: In metabolic studies, both greater carbohydrate intakes and higher
      glycemic indexes (GIs) raise fasting triacylglycerol concentrations. In
      epidemiologic studies, dietary glycemic load (GL) is positively associated with
      risk of coronary artery disease and type 2 diabetes. OBJECTIVE: We examined both
      the physiologic relevance of GI and GL and the ability of dietary questionnaires
      to measure these variables. DESIGN: In the Nurses' Health Study, we measured
      plasma triacylglycerol concentrations in fasting blood samples from 185 healthy
      postmenopausal women and HDL-cholesterol concentrations in an additional 95
      nonfasting samples. Dietary carbohydrate, GI, and GL were assessed by use of
      semiquantitative food-frequency questionnaires. The cross-sectional associations
      between these 3 variables and plasma triacylglycerol and HDL were assessed, with
      adjustment for potential confounding factors. RESULTS: For the lowest and highest
      quintiles of GL, the multivariate-adjusted geometric mean triacylglycerol
      concentrations were 0.98 and 1.75 mmol/L (87 and 155 mg/dL; P for trend < 0.001).
      Both overall GI (P for trend = 0.03) and carbohydrate (P for trend < 0.01)
      contributed independently to the strong positive association between GL and
      fasting triacylglycerol concentrations. GL was also inversely associated with HDL
      cholesterol concentrations. For the lowest and highest quintiles of GL, the mean
      HDL-cholesterol concentrations were 1.50 and 1.34 micromol/L (58 and 52 mg/dL; P
      for trend = 0.03). The relation between GL and fasting triacylglycerol
      concentrations differed significantly by body mass index (BMI; in kg/m(2))
      categories (P < 0.001 for interaction). For the lowest to the highest quintiles
      of GL, the mean triacylglycerol concentrations were 0.92 and 2.24 mmol/L (81 and
      198 mg/dL) in women with BMIs > 25 (P for trend < 0.001) and 1.02 and 1.42 mmol/L
      (90 and 126 mg/dL) in women with BMIs < or = 25 (P for trend < 0.001).
      CONCLUSION: These data support the physiologic relevance of the GL as a potential
      risk factor for coronary artery disease in free-living women, particularly those
      prone to insulin resistance. These findings also document the ability of a
      semiquantitative food-frequency questionnaire to assess dietary GIs and GLs.

PMID- 11237933
TI  - Simple skinfold-thickness measurements complement conventional anthropometric
      assessments in predicting glucose tolerance.
AB  - BACKGROUND: Skinfold-thickness measurements are considered to have limited
      clinical utility. OBJECTIVE: To assess whether skinfold-thickness measurements
      may be a useful adjunct to conventional anthropometric assessments in predicting
      glucose and insulin regulation, we studied responses to replicate 75-g oral
      glucose-tolerance tests (OGTTs) and performed simple anthropometry in a cross
      section of subjects. DESIGN: Thirty-five subjects completed the study: 11 lean
      [mean (+/-SEM) age: 33 +/- 3.2 y; body mass index (BMI; in kg/m(2)): 24.1 +/-
      0.8; and percentage body fat (%BF): 11.5 +/- 1.5%], 12 normal-weight (age: 33 +/-
      2.9 y; BMI: 23.9 +/- 0.7; and %BF: 24.3.5 +/- 1.3%), and 12 obese (age: 41 +/-
      4.5 y; BMI: 34.5 +/- 1.7; and %BF: 34.2 +/- 1.5%) individuals. The lean and
      normal-weight groups were selected to have similar BMIs but different %BFs. We
      measured the participants' heights, weights, %BFs, waist circumferences, hip
      circumferences, and truncal and peripheral skinfold thicknesses. Subjects
      received nine 75-g OGTTs and blood samples were collected at 0, 15, 30, 45, 60,
      90, and 120 min. Mean plasma glucose and insulin values were used to calculate
      the insulin sensitivity index. RESULTS: The obese group had higher plasma glucose
      concentrations and areas under the curve (AUCs) than did the normal-weight or
      lean group and higher plasma insulin concentrations and AUCs than did the lean
      group (P < 0.05). Stepwise multiple regression, with adjustment for demographic
      and anthropometric measurements, identified the following predictors: waist
      circumference, peripheral skinfold thickness, and BMI for fasting plasma glucose
      (partial R(2) = 0.20, 0.13, and 0.13, P < 0.05); waist circumference and truncal
      skinfold thickness for plasma glucose AUC (partial R(2) = 0.20 and 0.13, P <
      0.05); age, waist-to-hip ratio, and peripheral skinfold thickness for fasting
      plasma insulin (partial R(2) = 0.26, 0.22, and 0.15, P < 0.05); truncal skinfold
      thickness for plasma insulin AUC (partial R(2) = 0.41, P < 0.001); and peripheral
      skinfold thickness for both 2-h plasma glucose (partial R(2) = 0.59, P < 0.001)
      and the insulin sensitivity index (partial R(2) = 0.49, P < 0.001). CONCLUSION:
      Skinfold-thickness measurements may complement other established measurements for
      predicting abnormal glucose and insulin regulation.

PMID- 11237934
TI  - Glycemic index in the diet of European outpatients with type 1 diabetes:
      relations to glycated hemoglobin and serum lipids.
AB  - BACKGROUND: Little is known about the variation of the glycemic index (GI) in the
      diet of European outpatients with type 1 diabetes and how the GI of a commonly
      consumed diet is associated with metabolic control. OBJECTIVE: The present study
      examined the calculated dietary GI of European outpatients with type 1 diabetes
      for possible relations to glycated hemoglobin (Hb A(1c)) and serum lipid
      concentrations. DESIGN: The relation of the GI (calculated from a 3-d dietary
      record) to Hb A(1c), serum cholesterol (total, LDL, and HDL), and fasting
      triacylglycerol was analyzed in 2810 people with type 1 diabetes from the
      EURODIAB Complications Study. RESULTS: The GI was independently related to Hb
      A(1c) (P = 0.0001). Compared with the highest GI quartile (median GI: 89),
      adjusted Hb A(1c) in the lowest GI quartile (median GI: 75) was 11% lower in
      patients from southern European centers and 6% lower in patients from northern,
      western, and eastern European centers. Of the serum lipids, only the HDL
      cholesterol in patients from these European centers was independently related to
      the GI (P = 0.002). In southern European centers, the consumption of pasta,
      temperate-climate fruit, white bread, and potatoes largely determined the
      patients' dietary GI, whereas in the northern, western, and eastern European
      centers, consumption of bread, potatoes, and temperate-climate fruit was most
      relevant. CONCLUSIONS: This study in European patients with type 1 diabetes
      showed that a lower dietary GI is related to lower Hb A(1c) concentrations,
      independently of fiber intake. The consumption of bread and pasta had the biggest
      effect on the overall dietary GI of European outpatients.

PMID- 11237935
TI  - High prevalence of lactose absorbers in Northern Sardinian patients with type 1
      and type 2 diabetes mellitus.
AB  - BACKGROUND: Increased intestinal lactase activity has been shown to occur in
      alloxan and streptozotocin diabetic rats. OBJECTIVE: The objective of this study
      was to determine whether increased intestinal lactase activity is present in
      humans with diabetes mellitus. DESIGN: We assessed the capacity to digest lactose
      by measuring breath-hydrogen production after oral administration of lactose in
      50 patients with type 1 diabetes, 50 patients with type 2 diabetes, and 50
      healthy control subjects from Sassari, Sardinia, Italy, a population
      characterized by a low prevalence of lactase persistence (lactose absorbers).
      RESULTS: Fourteen percent of control subjects were lactose absorbers, compared
      with 48% of patients with type 1 diabetes and 52% of patients with type 2
      diabetes (P < 0.005). The odds ratio of lactase persistence in patients with type
      1 diabetes was 5.3 (95% CI: 2.0, 14.0) and in patients with type 2 diabetes was
      5.5 (95% CI: 2.1, 14.5). CONCLUSIONS: Diabetes is associated with increased
      intestinal lactase activity in humans. Consequently, there is a greater exposure
      to glucose and galactose in diabetic patients with high lactose consumption. This
      may explain the association between diabetes and the risk of cataract.

PMID- 11237936
TI  - Serum retinol distributions in residents of the United States: third National
      Health and Nutrition Examination Survey, 1988-1994.
AB  - BACKGROUND: Inadequate vitamin A status has been a potential nutritional problem
      for some segments of the US population, particularly children and the poor.
      OBJECTIVE: We evaluated serum retinol concentration by using population
      representative data from 16058 participants aged 4 to >/=90 y in the third
      National Health and Nutrition Examination Survey, 1988-1994. DESIGN: We used
      multivariate regression to examine the simultaneous associations of
      sociodemographic, biologic, and behavioral factors with serum retinol
      concentration. RESULTS: In children, serum retinol concentrations were greater
      with greater age, body mass index, serum lipids, and the use of supplements
      containing vitamin A. In adults, male sex, serum lipids, alcohol consumption, and
      age were positively associated with serum retinol concentration in most
      racial/ethnic strata. Household income was not associated with serum retinol
      concentration in children; associations were inconsistent in adults. The
      prevalence of serum retinol <0.70 micromol/L was very low in all strata; the
      prevalence of serum retinol <1.05 micromol/L was 16.7-33.9% in children aged 4-8
      y and 3.6-14.2% in children aged 9-13 y, depending on sex and racial/ethnic
      group. The prevalence of serum retinol<1.05 micromol/L was higher in non-Hispanic
      black and Mexican American children than in non-Hispanic white children; these
      differences remained significant (P < 0.0001) after covariates were controlled
      for. Among adults, nonwhite women were significantly (P < 0.0001) more likely
      than white women to have serum retinol <1.05 micromol/L after covariates were
      controlled for. CONCLUSIONS: Clinically low serum retinol concentration is
      uncommon in US residents aged > or = 4 y, although racial/ethnic and
      socioeconomic differences in serum retinol concentration still exist.

PMID- 11237937
TI  - Retinol binding protein as a surrogate measure for serum retinol: studies in
      vitamin A-deficient children from the Republic of the Marshall Islands.
AB  - BACKGROUND: Serum retinol is transported by retinol binding protein (RBP), which
      has one high-affinity binding site for retinol; consequently, the molar ratio of
      retinol to RBP in the circulation is approximately 1 to 1. In vitamin A
      deficiency (VAD), both serum retinol and RBP decline. However, the retinol-RBP
      relation has not been well studied in populations with a high incidence of severe
      VAD. OBJECTIVE: The purpose of this study was to determine whether RBP is a good
      surrogate for serum retinol at the very low retinol concentrations encountered in
      VAD. DESIGN: The stoichiometric relation between retinol and RBP was studied in
      239 Marshallese children: 65 with severe VAD (< or = 0.35 micromol retinol/L), 94
      with moderate VAD (0.36-0.70 micromol retinol/L), and 80 with vitamin A
      sufficiency (> 0.70 micromol retinol/L). RESULTS: Excellent correlation between
      retinol and RBP (r = 0.94) was observed across all retinol concentrations. Severe
      VAD was predicted with 96% sensitivity and 91% specificity on the basis of an RBP
      cutoff of < or = 0.48 micromol/L, whereas moderate VAD was predicted with 87%
      sensitivity and 98% specificity on the basis of an RBP cutoff of < or = 0.70
      micromol/L. CONCLUSIONS: The use of RBP results in the classification of
      essentially the same children with VAD as does retinol, and RBP is an excellent
      surrogate for serum retinol. Considering the relative ease of measuring RBP with
      immunodiagnostic kits compared with that of serum retinol by HPLC, the use of RBP
      concentrations to assess VAD may be particularly advantageous in field settings.
      Consequently, measuring RBP concentrations may be a practical alternative to
      measuring serum retinol in population surveys assessing the prevalence of VAD.

PMID- 11237938
TI  - Diminished and erratic absorption of ergocalciferol in adult cystic fibrosis
      patients.
AB  - BACKGROUND: Osteoporosis diminishes the quality of life in adults with cystic
      fibrosis (CF). Vitamin D deficiency resulting from malabsorption may be a factor
      in the etiology of low bone mineral density (BMD) in patients with CF. OBJECTIVE:
      Absorption of oral ergocalciferol (vitamin D2) and the consequent response of 25
      hydroxyvitamin D in 10 adults with CF and exocrine pancreatic insufficiency was
      compared with that of 10 healthy control subjects. DESIGN: In this
      pharmacokinetic study, CF patients and control subjects were pair-matched on age,
      sex, and race. Each subject consumed 2500 microg oral vitamin D2 with a meal. The
      CF group also took pancreatic enzymes that provided > or = 80000 U lipase. Blood
      samples were obtained at baseline and at 5, 10, 24, 30, and 36 h after vitamin D2
      consumption to measure serum vitamin D2 and 25-hydroxyvitamin D concentrations.
      RESULTS: Vitamin D2 concentrations in all subjects were near zero at baseline. CF
      patients absorbed less than one-half the amount of oral vitamin D2 that was
      absorbed by control subjects (P < 0.001). Absorption by the CF patients varied
      greatly; 2 patients absorbed virtually no vitamin D2. The rise in 25
      hydroxyvitamin D in response to vitamin D2 absorption was significantly lower
      over time in the CF group than in the control group (P = 0.0012). CONCLUSIONS:
      Vitamin D2 absorption was significantly lower in CF patients than in control
      subjects. These results may help explain the etiology of vitamin D deficiency in
      CF patients, which may contribute to their low BMD.

PMID- 11237939
TI  - Green tea or rosemary extract added to foods reduces nonheme-iron absorption.
AB  - BACKGROUND: Phenolic compounds act as food antioxidants. One of the postulated
      mechanisms of action is chelation of prooxidant metals, such as iron. Although
      the antioxidative effect is desirable, this mechanism may impair the utilization
      of dietary iron. OBJECTIVE: We sought to determine the effect of phenolic-rich
      extracts obtained from green tea or rosemary on nonheme-iron absorption. DESIGN:
      Young women aged 19-39 y consumed test meals on 4 separate occasions. The meals
      were identical except for the absence (meal A) or presence (meal B) of a phenolic
      rich extract from green tea (study 1; n = 10) or rosemary (study 2; n = 14). The
      extracts (0.1 mmol) were added to the meat component of the test meals. The meals
      were extrinsically labeled with either 55Fe or 59Fe and were consumed on 4
      consecutive days in the order ABBA or BAAB. Iron absorption was determined by
      measuring whole-body retention of 59Fe and the ratio of 55Fe to 59Fe activity in
      blood samples. RESULTS: The presence of the phenolic-rich extracts resulted in
      decreased nonheme-iron absorption. Mean (+/-SD) iron absorption decreased from
      12.1 +/- 4.5% to 8.9 +/- 5.2% (P < 0.01) in the presence of green tea extract and
      from 7.5 +/- 4.0% to 6.4 +/- 4.7% (P < 0.05) in the presence of rosemary extract.
      CONCLUSION: Phenolic-rich extracts used as antioxidants in foods reduce the
      utilization of dietary iron.

PMID- 11237940
TI  - Determinants of plasma total homocysteine concentration in the Framingham
      Offspring cohort.
AB  - BACKGROUND: Established determinants of fasting total homocysteine (tHcy)
      concentration include folate and vitamin B-12 status, serum creatinine
      concentration, and renal function. OBJECTIVE: Our objective was to examine the
      relation between known and suspected determinants of fasting plasma tHcy in a
      population-based cohort. DESIGN: We examined the relations between fasting plasma
      tHcy concentrations and nutritional and other health factors in 1960 men and
      women, aged 28-82 y, from the fifth examination cycle of the Framingham Offspring
      Study between 1991 and 1994, before the implementation of folic acid
      fortification. RESULTS: Geometric mean tHcy was 11% higher in men than in women
      and 23% higher in persons aged > or = 65 y than in persons aged < 45 y (P <
      0.001). tHcy was associated with plasma folate, vitamin B-12, and pyridoxal
      phosphate (P for trend < 0.001). Dietary folate, vitamin B-6, and riboflavin were
      associated with tHcy among non-supplement users (P for trend < 0.01). The tHcy
      concentrations of persons who used vitamin B supplements were 18% lower than
      those of persons who did not (P < 0.001). tHcy was positively associated with
      alcohol intake (P for trend = 0.004), caffeine intake (P for trend < 0.001),
      serum creatinine (P for trend < 0.001), number of cigarettes smoked (P for trend
      < 0.001), and antihypertensive medication use (P < 0.001). CONCLUSIONS: Our study
      confirmed, in a population-based setting, the importance of the known
      determinants of fasting tHcy and suggested that other dietary and lifestyle
      factors, including vitamin B-6, riboflavin, alcohol, and caffeine intakes as well
      as smoking and hypertension, influence circulating tHcy concentrations.

PMID- 11237941
TI  - Evaluation of the relation between n-3 and n-6 fatty acid status and parity in
      nonpregnant women from the Netherlands.
AB  - BACKGROUND: We previously observed an inverse relation between parity and
      docosahexaenoic acid (DHA) status in pregnant women in the Netherlands. This
      implies that maternal DHA status may not fully normalize after a mature
      pregnancy. OBJECTIVE: The objective was to investigate the relation between the
      essential fatty acid status (in particular the DHA status) of nonpregnant women
      and the number of completed pregnancies and whether the number of previous
      pregnancies is associated with a lower DHA status in women from the Netherlands.
      DESIGN: This was a cross-sectional study of 129 healthy nonpregnant women who
      completed 0, 1, 2, 3, or 4 mature, uncomplicated, singleton pregnancies. RESULTS:
      The relative amount of DHA in the plasma phospholipids of nulliparous women and
      of mothers who completed 1-4 pregnancies (duration since last pregnancy: 3.9 +/-
      2.4 y) was not significantly different; a significant correlation between parity
      and the percentage of DHA in the phospholipids was not observed either. The
      percentage of DHA in the phospholipids of erythrocytes of mothers was
      significantly lower than the percentage in the erythrocytes of the nulliparas (P
      = 0.013), but no significant correlation between the percentage of DHA in the
      phospholipids of erythrocytes and parity was found. The time interval between the
      different pregnancies did not influence maternal DHA status. CONCLUSIONS: No
      relation was found between DHA status and parity in the nonpregnant Dutch women
      whose last pregnancy was completed > or = 1 y previously. Maternal DHA status, as
      reflected in plasma and erythrocyte phospholipids, probably normalized within 1 y
      after the last partus. Whether this is true for other tissues remains to be
      determined.

PMID- 11237942
TI  - Association of folate intake and serum homocysteine in elderly persons according
      to vitamin supplementation and alcohol use.
AB  - BACKGROUND: The serum total homocysteine concentration (tHcy), an indicator of
      folate status and a possible risk factor for vascular disease, is elevated with
      impaired renal function and poor vitamin B-12 status, which are common in the
      elderly. OBJECTIVE: Our objective was to determine the association between tHcy,
      folate intake, alcohol consumption, and other lifestyle factors in elderly
      persons. DESIGN: This cross-sectional study used linear regression to model
      changes in tHcy. Subjects were 278 men and women aged 66-94 y studied in 1993.
      RESULTS: Total folate intake was negatively associated with tHcy in models
      adjusted for age, sex, serum creatinine, and serum albumin. We found an
      interaction between food folate intake and supplement use. Food folate intake had
      an inverse dose-response relation with tHcy that was limited to nonusers of
      supplements. Predicted tHcy was 1.5 micromol/L lower in users of supplements
      containing folate and vitamin B-12 than in nonusers and was independent of food
      folate intake. We found a positive dose-response relation of coffee and tea
      intake with tHcy, a positive association for alcohol intake of > or = 60
      drinks/mo compared with low intake, and an interaction of alcohol use with folate
      intake and supplement use. Compared with alcohol users, nonusers had higher
      predicted tHcy and a lower inverse dose-response relation of food folate intake
      with tHcy. CONCLUSIONS: The inverse association between folate intake and tHcy
      was strongest among nonusers of supplements and among alcohol drinkers.
      Identifying modifiable factors related to tHcy, a possible risk factor for
      vascular disease, is especially important in elderly persons.

PMID- 11237943
TI  - Iron status of the free-living, elderly Framingham Heart Study cohort: an iron
      replete population with a high prevalence of elevated iron stores.
AB  - BACKGROUND: Although iron deficiency occurs commonly in vulnerable groups of
      women of reproductive age, infants, and children, less is known about the iron
      nutriture of the elderly. OBJECTIVE: Our objective was to evaluate the iron
      status of a noninstitutionalized, elderly US population, with a particular focus
      on 2 concerns unique to the elderly: 1) potential confounding effects of chronic
      disease on iron measures and 2) increased occurrence of elevated iron stores.
      DESIGN: Multiple iron measures, including serum ferritin (SF), transferrin
      saturation, mean cell volume, and hemoglobin, were used to evaluate the
      prevalence of iron deficiency (ID), iron deficiency anemia (IDA), and other
      measures of iron nutriture in 1016 elderly white Americans aged 67-96 y from the
      Framingham Heart Study. "Diseased" subjects were defined as those with possible
      pathologically altered iron measures due to inflammation, infection, elevated
      liver enzymes, hereditary hemochromatosis, or cancer. The effect of altered iron
      status on various prevalence estimates was assessed. RESULTS: The elderly
      subjects had a low prevalence of ID (2.7%), IDA (1.2%), and depleted iron stores
      (3%; SF < 12 microg/L). In contrast, 12.9% had elevated iron stores (SF > 300
      microg/L in men and SF > 200 microg/L in women), of which only 1% was
      attributable to chronic disease. The prevalence of ID, IDA, and depleted iron
      stores was unaffected by the presence of chronic disease. CONCLUSIONS: The
      Framingham Heart Study cohort is an iron-replete elderly population with a high
      prevalence of elevated iron stores in contrast with a low prevalence of iron
      deficiency, with insignificant effects of chronic disease on these iron status
      estimates. The likely liability in iron nutriture in free-living, elderly white
      Americans eating a Western diet is high iron stores, not iron deficiency.

PMID- 11237944
TI  - Plasma free amino acid concentrations in healthy Guatemalan adults and in
      patients with classic dengue.
AB  - BACKGROUND: Plasma free amino acid patterns in health and disease have been
      reported. However, amino acid concentrations in adult populations in developing
      countries and in patients with dengue, as a model for an acute infectious viral
      disease endemic to the tropics, have not been reported. OBJECTIVE: The purpose of
      this study was to determine the amino acid profile in both healthy Guatemalan
      adults from different socioeconomic backgrounds and at 3 time points during the
      course of classic dengue. DESIGN: The study was carried out in Guatemala and
      included measurement of plasma free amino acids in 22 healthy control subjects
      (14 low income, 8 middle class) and 17 febrile patients. Measurements of amino
      acids were repeated within a 48-h interval in 20 of the healthy Guatemalans. In 9
      patients with dengue, amino acids were assayed 3 times: on admission to a local
      hospital in the coastal plain of Guatemala, on hospital discharge, and 7 d after
      hospital discharge. RESULTS: Branched-chain amino acid concentrations in healthy
      adults and dengue patients in Guatemala were lower than normal values reported in
      the literature for healthy Swedish adults. With the exception of increased
      phenylalanine concentrations and an increased ratio of phenylalanine to tyrosine,
      all amino acids as well as the Fischer molar ratio were decreased in the acute
      phase of dengue. CONCLUSIONS: Healthy Guatemalans have different amino acid
      patterns than do Swedish subjects independent of socioeconomic status. The
      systemic viral disease dengue is associated with changes in the plasma free amino
      acid pattern, reflecting infection-related alterations in amino acid metabolism.

PMID- 11237946
TI  - Issues raised by psyllium meta-analysis.

PMID- 11237947
TI  - Ross Conference had too narrow a representation to speak about matters of the
      world.

PMID- 11237948
TI  - Metabolic response to weight loss.

PMID- 11237951
TI  - Fecal folate.

PMID- 11237953
TI  - Calcium and vitamin D intakes and blood pressure.

PMID- 11237955
TI  - Dairy consumption and bone health.

PMID- 11237956
TI  - Abnormal fatty acid status in patients with Crohn disease.

PMID- 11237957
TI  - The salt controversy at the turn of the century: no to prejudiced thinking, yes
      to concerted action.

PMID- 11237960
TI  - "He was never quite 'himself' after that accident": exploring the long-term
      consequences of mild traumatic brain injury.

PMID- 11237961
TI  - Retinoblastoma: clinical presentation and the role of neuroimaging.

PMID- 11237962
TI  - Reporting lumbar disk abnormalities: at last, consensus!

PMID- 11237963
TI  - Experimental MR imaging-guided interstitial cryotherapy of the brain.
AB  - BACKGROUND AND PURPOSE: Hyperthermal ablation techniques such as laser or RF
      ablation require dedicated heat-sensitive MR imaging sequences for monitoring MR
      imaging--guided interventions. Because cryotherapy does not have these
      limitations, the purpose of this study was to evaluate the feasibility of MR
      imaging--guided percutaneous cryotherapy of the brain. METHODS: An experimental
      cryoprobe with an outer diameter of 2.7 mm was inserted into the right frontal
      lobe of 11 healthy pigs under MR imaging control. Freezing procedures were
      monitored by using an interventional 1.5-T magnet and a gradient-echo sequence
      with radial k-space trajectories, a fast T2-weighted single-shot spin-echo
      sequence, and a T1-weighted single-shot gradient-echo sequence. In three animals,
      the procedure was also monitored by using dynamic CT. A freeze-thaw cycle with a
      duration of 3 minutes was repeated three times per animal. Follow-up MR images
      were obtained 3, 7, and 14 days after cryotherapy by using conventional MR
      sequences. Six animals were killed 7 days after intervention, and five animals
      were killed 14 days after intervention. The brains were sectioned, and the
      histologic findings of the lesions were compared with the MR imaging appearance.
      RESULTS: No artifacts due to the probe were observed on the MR images or CT
      scans. The ice formation (mean diameter, 12.5 mm) was very well delineated as a
      signal-free sphere. MR monitoring of the freezing procedure yielded a
      significantly higher ice:tissue contrast than did CT. The size of the ice ball as
      imaged by MR imaging and CT during the intervention correlated well with the MR
      imaging appearance of the lesions at the 14-day follow-up examination and with
      the histologic findings. Histologically, coagulation necrosis and gliosis were
      found, surrounded by a transition zone of edema and a disrupted blood-brain
      barrier, corresponding to a contrast-enhancing rim around the lesions on follow
      up MR images. CONCLUSION: MR imaging-guided cryotherapy of the brain is possible
      and allows a precise prediction of the resulting necrosis. MR imaging of the
      freezing process does not require heat-sensitive sequences and is superior to CT
      for monitoring of cryoablation.

PMID- 11237964
TI  - MR imaging, single-photon emission CT, and neurocognitive performance after mild
      traumatic brain injury.
AB  - BACKGROUND AND PURPOSE: Mild traumatic brain injury (mTBI) (Glasgow Coma Scale =
      14-15) is a common neurologic disorder and a common cause of neurocognitive
      deficits in the young population. Most patients recover fully from mTBI, but 15%
      to 29% of patients have persistent neurocognitive problems. Although a partially
      organic origin is considered likely, little brain imaging evidence exists for
      this assumption. The aims of the present study were to establish the prevalence
      of posttraumatic lesions in mTBI patients on MR images and to assess the relation
      between these imaging findings and posttraumatic symptoms. Secondly, we explored
      the value of early posttraumatic single-photon emission CT (SPECT) for the
      evaluation of mTBI. METHODS: Twenty-one consecutive patients were included in the
      study. Patients underwent MR examination, technetium-99m hexamethylpropylene
      amine oxime SPECT, and neurocognitive assessment within 5 days after injury.
      Neurocognitive follow-up was conducted 2 and 6 months after injury, and MR
      imaging was repeated after 6 months. Lesion size and brain atrophy were measured
      on the MR studies. RESULTS: Twelve (57%) of 21 patients had abnormal MR findings,
      and 11 (61%) of 18 had abnormal SPECT findings. Patients with abnormal MR or
      SPECT findings had brain atrophy at follow-up. The mean neurocognitive
      performance of all subjects was within normal range. There was no difference in
      neurocognitive performance between patients with normal and abnormal MR findings.
      Patients with abnormal MR findings only showed significantly slower reaction
      times during a reaction-time task. Seven patients had persistent neurocognitive
      complaints and one patient met the criteria for a postconcussional syndrome.
      CONCLUSION: Brain lesions are common after mTBI; up to 77% of patients may have
      abnormal findings either on MR images or SPECT scans, and these lesions may lead
      to brain atrophy. The association between hypoperfusion seen on acute SPECT and
      brain atrophy after 6 months suggests the possibility of (secondary) ischemic
      brain damage. There is only a weak correlation between neuroimaging findings and
      neurocognitive outcome.

PMID- 11237965
TI  - Evidence for cytotoxic edema in the pathogenesis of cerebral venous infarction.
AB  - BACKGROUND AND PURPOSE: The pathogenesis of cerebral venous infarction (CVI)
      remains controversial, with uncertainty over whether cytotoxic edema plays a
      role. Recent animal studies have shown that cytotoxic edema reliably occurs in
      acute CVI and precedes the onset of vasogenic edema. Our hypothesis was that
      cytotoxic edema would also occur in acute human CVI and would be detectable as an
      area of restricted diffusion on diffusion-weighted images. METHODS: Twelve
      subjects with acute cerebral venous thrombosis confirmed by MR venography
      underwent both conventional MR and echo-planar diffusion-weighted imaging
      (maximum diffusion sensitivity [b=1000 s/mm(2)]). Images were examined for areas
      of CVI that were identified as T2 hyperintensity, diffusion hyperintensity, or
      hemorrhage. The percent change in apparent diffusion coefficient (ADC) and T2
      signal as well as the T2/diffusion volume were calculated within areas of
      edematous CVI. Regression techniques were used to examine the relationship of
      these variables to symptom duration. RESULTS: Ten regions of CVI were detected in
      seven subjects, all showing T2 hyperintensity. Two of these regions were
      predominantly hemorrhagic and did not display diffusion hyperintensity. The
      remaining eight regions displayed diffusion hyperintensity that was associated
      with a decreased ADC. ADC values increased with symptom duration (r(2) = 0.96; P
      <.006). Both T2 hyperintensity and T2/diffusion volume peaked approximately 2
      days after symptom onset. CONCLUSION: Restricted water diffusion suggesting
      cytotoxic edema is commonly found in subjects with acute CVI and decreases over
      time. This supports an important etiologic role for cytotoxic edema in the
      pathogenesis of CVI.

PMID- 11237966
TI  - Diffusion anisotropy of the internal capsule and the corona radiata in
      association with stroke and tumors as measured by diffusion-weighted MR imaging.
AB  - BACKGROUND AND PURPOSE: Diffusion-weighted MR images have enabled measurement of
      directionality of diffusion (anisotropy) in white matter. To investigate
      differences in the anisotropy for various types of pathologic findings and the
      association between the anisotropy of tracts and neurologic dysfunction, we
      compared the anisotropy of the posterior limb of the internal capsule and the
      corona radiata between patients with stroke and those with tumors and between
      patients with and without hemiparesis. METHODS: Thirty-three patients consisting
      of 11 with tumors and 22 with ischemic disease (16 acute infarction, four old
      infarction, and two transient ischemic attack) and nine control patients were
      studied with a 1.5-T MR imager. Diffusion-weighted images were obtained with
      diffusion gradients applied in three orthogonal directions. The diffusion
      anisotropy measurements were obtained from regions of interests defined within
      the internal capsule and the corona radiata. RESULTS: The diffusion anisotropy
      was significantly reduced in all internal capsules and coronae radiata involved
      by infarcts, tumors, and peritumoral edema compared with that of the control
      patients (P <.0001). This reduction was most prominent in the tracts involved by
      tumors (P <.05). The anisotropy of the internal capsules and coronae radiata was
      significantly decreased in cases with moderate-to-severe hemiparesis as compared
      with those with no or mild hemiparesis (P <.0001). Diffusion anisotropy tended to
      be also reduced in normal-appearing internal capsules and coronae radiata that
      were remote from the involved segment of the corticospinal tract. CONCLUSION: The
      degree of impaired diffusion anisotropy may vary in different pathologic
      conditions and correlate with neurologic dysfunction. The measurement of
      diffusion anisotropy may provide additional information relating to neurologic
      function and transneuronal effects.

PMID- 11237967
TI  - Chordoid glioma: a neoplasm unique to the hypothalamus and anterior third
      ventricle.
AB  - BACKGROUND AND PURPOSE: Chordoid glioma is a new clinicopathologic entity that
      occurs in the region of the hypothalamus/anterior third ventricle. The aims of
      this study were to describe the characteristic radiographic features of chordoid
      glioma, identify specific imaging features that may enable differentiation of
      chordoid glioma from other suprasellar tumors, and increase neuroradiologists'
      awareness of this newly described tumor, facilitating prospective diagnosis.
      METHODS: CT scans and/or MR images of six patients with chordoid glioma were
      reviewed retrospectively to determine whether any characteristic radiographic
      features would emerge. Reports of the clinical presentation, pathologic findings,
      and radiographic findings of another six patients were reviewed and included, for
      a total patient population of 12 (mean age +/- SD, 46 +/- 13 years). RESULTS:
      Imaging features were strikingly similar for all tumors. In each case, the mass
      was ovoid, was well circumscribed, was located in the region of the
      hypothalamus/anterior third ventricle, and enhanced uniformly and intensely.
      Tumors were hyperdense to gray matter on CT scans and were isointense on T1
      weighted MR images and slightly hyperintense on long-TR MR images. In two
      patients, vasogenic edema extended into the optic tracts, and in three, there was
      hydrocephalus. CONCLUSION: Chordoid glioma is a recently described unique
      histopathologic entity that has been added to the World Health Organization
      glioma classification scheme and must be included in the differential diagnosis
      of a suprasellar mass. Distinctive imaging features are its location, ovoid
      shape, hyperdensity on CT scans, and uniform intense contrast enhancement.

PMID- 11237968
TI  - Magnetization transfer ratio histogram analysis of gray matter in relapsing
      remitting multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: Gray matter may be affected by multiple sclerosis (MS), a
      white matter disease. Magnetization transfer ratio (MTR) is a sensitive and
      quantitative marker for structural abnormalities, and has been used frequently in
      the imaging of MS. In this study, we evaluated the amount of MTR of gray matter
      among patients with relapsing-remitting MS and healthy control subjects as well
      as the correlation between gray matter MTR abnormality and neurologic disability
      associated with relapsing-remitting MS. METHODS: We obtained fast spin-echo dual
      echo and magnetization transfer (with and without MT saturation pulses) images
      from eighteen patients with relapsing-remitting MS and 18 age-matched healthy
      control subjects. Gray matter was segmented using a semiautomated system. Gray
      matter MTR histogram parameters, Kurtzke Expanded Disability Status Scale (EDSS),
      total T2 lesion volume, and gray matter volumes were obtained for statistical
      analysis. RESULTS: A significant difference was found in gray matter MTR between
      patients with relapsing-remitting MS and healthy subjects (mean and median). Gray
      matter MTR histogram normalized peak heights in patients inversely correlated
      with EDSS (r = -0.65, P =.01). There was also an inverse correlation between mean
      MTR of gray matter and total T2 lesion volume. CONCLUSION: The MTR of gray matter
      significantly differed between patients with relapsing-remitting MS and healthy
      control subjects, suggesting that MS is a more diffuse disease affecting the
      whole brain, and neuronal damage accumulates in step with T2 lesion volume. Our
      finding of the relationship between gray matter MTR and EDSS indicates that
      measurement of gray matter abnormality may be a potentially useful tool for
      assessing clinical disability in MS.

PMID- 11237969
TI  - Neurovascular contact of the brain stem in hypertensive and normotensive
      subjects: MR findings and clinical significance.
AB  - BACKGROUND AND PURPOSE: About 20 years ago, a theory was put forward that
      neurovascular contact of the root entry zone (REZ) of the ninth and 10th cranial
      nerve is responsible for elevated blood pressure in patients with essential
      hypertension. To test this hypothesis, we used MR tomography and MR angiography
      to evaluate the presence and degree of neurovascular contact of the REZ of the
      ninth and 10th cranial nerves in patients with essential hypertension as compared
      with patients with renal parenchymal hypertension and normotensive healthy
      volunteers. METHODS: Patients with essential hypertension (group 1; n = 33),
      renal parenchymal hypertension (group 2; n = 30), and normotensive healthy
      volunteers (group 3; n = 25) underwent high-resolution (axial and coronal) brain
      stem MR imaging and MR angiography. The images were interpreted consensually by
      two radiologists who were blinded to the patients' hypertensive status.
      Neurovascular contact was graded as vessel contact without associated brain stem
      deformity (grade I), vessel contact with associated brain stem deformity (grade
      II), or vessel contact with associated deformity and displacement of the brain
      stem (grade III). RESULTS: Neurovascular contact of the REZ of the ninth and 10th
      cranial nerve on the left side was found in 48.5% in group 1, in 26.7% in group
      2, and in 48.0% in group 3. The rate of neurovascular contact on the right side
      was 24.2%, 13.3%, and 40.0%, respectively. chi(2) analysis showed no statistical
      difference between the groups. CONCLUSION: Neurovascular contact is not more
      frequent in patients with essential hypertension than in normotensive control
      subjects or in those with secondary hypertension; therefore, MR imaging cannot
      aid patient selection for neurosurgical vascular decompression.

PMID- 11237971
TI  - Diffuse lesions in the CNS revealed by MR imaging in a case of Whipple disease.
AB  - SUMMARY: We report a case of Whipple disease involving the brain, optic chiasm,
      posterior fossa, and spinal cord. We evaluate the role of MR imaging for initial
      evaluation and for long-term follow-up of Whipple disease involving the CNS. We
      also discuss the semiologic characteristics of the lesions.

PMID- 11237970
TI  - Evaluation of the intracranial dural sinuses with a 3D contrast-enhanced MP-RAGE
      sequence: prospective comparison with 2D-TOF MR venography and digital
      subtraction angiography.
AB  - BACKGROUND AND PURPOSE: The diagnosis of dural sinus thrombosis is often
      difficult because of its variable and nonspecific clinical presentation and the
      overlapping signal intensities of thrombosis and venous flow on conventional MR
      images and MR venograms. We compared 3D contrast-enhanced magnetization-prepared
      rapid gradient-echo (MP-RAGE) sequences with 2D time-of-flight (TOF) MR
      venography, digital subtraction angiography (DSA), and conventional spin-echo
      (SE) MR imaging for the assessment of normal and abnormal dural sinuses. METHODS:
      In a phantom study, a plastic tube with pulsating flow was used to simulate the
      intracranial dural sinus. With 3D MP-RAGE, a variety of flow velocities, contrast
      material concentrations, and angulations between the phantom flow tube and the
      plane of acquisition were tested to measure their relationship to signal-to-noise
      ratio (SNR). In a clinical study, 35 patients, including 18 with suspected dural
      sinus thrombosis, were studied with both MR imaging and DSA. Receiver operating
      characteristic (ROC) analysis was performed in a blinded fashion using DSA as the
      reference standard. RESULTS: With the phantom, the SNR of flow increased with
      increasing contrast concentration, but was not affected by the angle between the
      tube and scan slab. There was no relationship between SNR and velocity when the
      contrast concentration was 1.0 mmol/L or greater. In the clinical study, dural
      sinus thrombosis as well as the normal anatomy of the dural sinuses were seen
      better with 3D contrast-enhanced MP-RAGE than with 2D-TOF MR venography. Three
      dimensional contrast-enhanced MP-RAGE showed the highest diagnostic confidence on
      ROC curves in the diagnosis of thrombosis. CONCLUSION: Three-dimensional contrast
      enhanced MP-RAGE is superior to 2D-TOF MR venography and conventional SE MR
      imaging in the depiction of normal venous structures and the diagnosis of dural
      sinus thrombosis, and is a potential alternative to DSA.

PMID- 11237972
TI  - Neurenteric cyst with alteration of signal intensity on follow-up MR images.
AB  - SUMMARY: Intracranial neurenteric cysts are uncommon and usually have low
      intensity on T1-weighted MR images and high intensity on T2-weighted MR images.
      We report a case of a neurenteric cyst that was situated in front of the medulla
      oblongata and the size of which increased with alteration of MR signal from high
      to isointense compared with that of brain on T1-weighted images obtained 33
      months after the initial MR images. We think that the signal change of the cyst
      was probably caused by a change of protein concentration.

PMID- 11237973
TI  - Sonographic, CT, and MR imaging findings in diffuse infiltrative retinoblastoma:
      report of two cases with histologic comparison.
AB  - SUMMARY: Diffuse infiltrating retinoblastoma is a rare form of retinoblastoma. We
      report two cases of this disease in which sonographic, CT, and MR imaging
      findings were compared with histologic studies obtained after enucleation.
      Although nonspecific, MR imaging provides valuable morphologic data for the
      diagnosis of diffuse infiltrating retinoblastoma and may help in decisions
      regarding enucleation.

PMID- 11237974
TI  - Malignant schwannoma of the trigeminal nerve.
AB  - SUMMARY: We present the MR imaging, CT, and clinical findings of a patient with
      malignant schwannoma of the trigeminal nerve. Local tumor recurrence is frequent
      and may be mistaken for lymphatic spread. In this report, we emphasize the
      natural history of this rare tumor and discuss the importance of imaging in
      diagnosis and surveillance.

PMID- 11237975
TI  - Unusual eustachian tube mass: glomus tympanicum.
AB  - SUMMARY: A case of recurrent glomus tympanicum presenting with epistaxis is
      described. CT and MR imaging revealed a homogeneously enhancing mass extending
      along the entire course of the eustachian tube, with a portion protruding into
      the nasopharynx. Glomus tumors tend to spread along the path of least resistance
      and may extend into the eustachian tube. The unique imaging appearance should
      place a glomus tumor high on the list of differential diagnoses.

PMID- 11237976
TI  - Parapharyngeal second branchial cyst manifesting as cranial nerve palsies: MR
      findings.
AB  - SUMMARY: We report the MR findings of parapharyngeal branchial cleft cyst
      manifesting as multiple, lower cranial nerve palsies in a 35-year-old woman. On
      MR images, a well-marginated cystic mass was detected in the right parapharyngeal
      space, with displacement of both the right internal carotid artery and the right
      internal jugular vein on the posterolateral side. The cyst contained a whitish
      fluid that was slightly hyperintense on T1-weighted images and slightly
      hypointense to CSF on T2-weighted images. No enhancement on contrast-enhanced T1
      weighted images was present. The right side of the tongue showed high signal
      intensity on T2-weighted images, suggesting denervation.

PMID- 11237977
TI  - Gray scale and power Doppler sonography in cases of Kimura disease.
AB  - SUMMARY: Kimura disease is a rare chronic inflammatory disorder mimicking
      malignancy. Nodes are present in the submental and submandibular regions, within
      the parotid gland, and in the upper cervical chain. On gray scale sonograms, they
      are hypoechoic and round, with normal hilar architecture and homogeneous internal
      echoes. On power Doppler sonograms, the nodes show prominent intranodal vessels
      with a hilar pattern and low intranodal resistance. The soft tissue and parotid
      lesions also show low-resistance vascularity within.

PMID- 11237978
TI  - Inflammatory myofibroblastic tumor involving the pterygopalatine fossa.
AB  - SUMMARY: Inflammatory myofibroblastic tumors (IMT) comprise a rare group of
      lesions characterized histologically by acute and chronic inflammatory cells with
      a variable degree of fibrous stroma. Occurrence in the extracranial head and neck
      in children is unusual, and involvement in the pterygopalatine fossa has not, to
      our knowledge, been reported as occurring in this age group. We present the CT
      findings of an IMT of the pterygopalatine fossa in a 6-year-old female patient
      with a 2-week history of fever and a painless swelling of the left cheek. The
      diagnosis of IMT should be included in the differential diagnosis of a child
      presenting with an aggressive mass associated with systemic features such as
      fever, elevated sedimentation rate, and leukocytosis.

PMID- 11237979
TI  - Bleeding complications after basilar artery fibrinolysis with tissue plasminogen
      activator.
AB  - BACKGROUND AND PURPOSE: Fibrinolysis with local intraarterial urokinase infusion
      for basilar artery thrombosis has been associated with a low rate of spontaneous
      symptomatic cerebral hemorrhage, even when patients have been treated late in the
      course of symptoms. Because urokinase is presently unavailable in the United
      States, this study was undertaken to determine the frequency of spontaneous
      cerebral hemorrhage in basilar artery fibrinolysis performed with tissue
      plasminogen activator (tPA). METHODS: In a retrospective review of our initial
      experience with cerebral fibrinolysis for acute stroke using intraarterial tPA,
      four cases of basilar thrombosis were identified. Doses of the fibrinolytic agent
      and heparin, angiographic findings, clinical courses, and bleeding complications
      for these patients were determined. These results were compared with those from a
      prior study of 20 similar consecutive patients treated with urokinase. RESULTS:
      Symptom duration before treatment was unlimited. Intraarterial doses of tPA were
      20 to 50 mg. Patients received full systemic anticoagulation with heparin.
      Complete basilar artery recanalization was achieved in 75% of patients. Two
      patients treated with tPA had angioplasty and stent placement for related high
      grade stenosis. Spontaneous symptomatic cerebral hemorrhage occurred in three
      (75%) of the four tPA-treated patients and in three (15%) of the 20 urokinase
      treated patients. CONCLUSION: The cerebral hemorrhage complication rate for
      intraarterial fibrinolysis with tPA was very high in cases of basilar artery
      thrombosis at the doses we used. Protocol adjustments should be considered.

PMID- 11237980
TI  - Rheolytic thrombectomy of the occluded internal carotid artery in the setting of
      acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Acute thromboembolic stroke complicated by ipsilateral
      carotid occlusion may present both mechanical and inflow-related barriers to
      effective intracranial thrombolysis. We sought to review our experience with a
      novel method of mechanical thrombectomy, in such cases, using the Possis AngioJet
      system, a rheolytic thrombectomy device. METHODS: A review of our interventional
      neuroradiology database revealed three patients in whom an occluded cervical
      internal carotid artery was encountered during endovascular treatment for acute
      stroke and in whom thrombectomy was attempted, using the 5F Possis AngioJet
      thrombectomy catheter. The medical records and radiographic studies of these
      patients were reviewed. RESULTS: Three patients were identified (ages, 52--84
      years). Two patients had isolated occlusion of the internal carotid artery; in
      one patient, thrombus extended down into the common carotid artery. Treatment was
      initiated within 190 to 360 minutes of stroke onset. Thrombectomy of the carotid
      artery was deemed necessary because of poor collateral flow to the affected
      hemisphere (chronic contralateral internal carotid artery occlusion [one patient]
      and thrombus extending to the carotid "T" [one patient]) or inability to pass a
      microcatheter through the occluded vessel (one patient). Adjunctive therapy
      included pharmacologic thrombolysis with tissue plasminogen activator (all
      patients), carotid angioplasty and stenting (two patients), and middle cerebral
      artery angioplasty (one patient). Patency of the carotid artery was reestablished
      in two patients, with some residual thrombus burden. In the third patient, the
      device was able to create a channel through the column of thrombus, allowing
      intracranial access. CONCLUSION: Rheolytic thrombectomy shows potential for
      rapid, large-burden thrombus removal in cases of internal carotid artery
      thrombosis, allowing expedient access to the intracranial circulation for
      additional thrombolytic therapy.

PMID- 11237981
TI  - Spontaneous obliteration of pial arteriovenous malformations: a review of 27
      cases.
AB  - BACKGROUND AND PURPOSE: Brain arteriovenous malformations (AVMs) occur in
      approximately 0.14% of the population. The most common presentations are
      hemorrhage (50%) and seizures (25%). Although they are congenital abnormalities,
      their angioarchitecture may vary over time. A rare but well-recognized phenomenon
      of AVMs is that of spontaneous obliteration. It is not known what factors
      predispose to spontaneous obliteration. The purpose of our study was to determine
      whether spontaneous thrombosis of AVMs can be predicted by their
      angioarchitecture and whether there is any risk of recurrence once obliteration
      has occurred. METHODS: We retrospectively reviewed the angiographic and cross
      sectional imaging data amassed over an 18-year period, including follow-up
      imaging studies and mail surveys of referring and family physicians. A control
      group was obtained from contemporaneous AVMs of a similar size. RESULTS: We
      identified 28 cases of spontaneous obliteration in a series of 2162 patients. The
      mean time between initial diagnostic angiography and angiographic obliteration
      was 10 months, during which time there was no intervention and no history of
      repeat hemorrhage; nor had hemorrhage recurred during the follow-up period (mean,
      53 months). Most of the AVMs were deep (22/27) with only one draining vein
      (21/27) and few feeding arteries. In more than half the cases (15/27) drainage
      was exclusively into the superficial venous system. CONCLUSION: Spontaneous
      obliteration is rare (1.3%). Common features include hemorrhagic presentation and
      few arterial feeding vessels. Although we found no instance of repeat hemorrhage
      during the follow-up period, AVMs can recanalize, and follow-up is therefore
      recommended.

PMID- 11237982
TI  - Transsphenoidal computer-navigation-assisted deflation of a balloon after
      endovascular occlusion of a direct carotid cavernous sinus fistula.
AB  - SUMMARY: A 49-year-old woman with a direct posttraumatic carotid cavernous
      fistula (CCF) was treated with detachable balloons via a transcarotid route.
      After the procedure, her intracranial bruit, conjunctival injection, and orbital
      congestion were cured, but the preexistent sixth nerve palsy deteriorated. CT
      showed one balloon positioned in the posterior portion of the right cavernous
      sinus and was regarded to be responsible for nerve compression. After surgical
      exposure by use of a transnasal-transsphenoidal approach under 3D navigation
      control, this balloon was deflated by puncture with a 22-gauge needle. The
      previously described symptoms resolved after balloon deflation. This report
      presents a rare complication of endovascular treatment of direct CCF and a new
      microsurgical approach to a balloon in a case of nerve compression.

PMID- 11237983
TI  - Alexander disease: diagnosis with MR imaging.
AB  - BACKGROUND AND PURPOSE: To date, the demonstration of Rosenthal fibers on brain
      biopsy or autopsy specimens is considered a prerequisite for a definitive
      diagnosis of Alexander disease. We initiated a multiinstitutional survey of MR
      abnormalities in both presumed and confirmed cases of Alexander disease to assess
      the possibility of an MR-based diagnosis. METHODS: MR imaging studies in three
      patients with an autopsy-based diagnosis of Alexander disease were analyzed to
      define MR criteria for the diagnosis. These criteria were then applied to 217
      children with leukoencephalopathy of unknown origin. RESULTS: Five MR imaging
      criteria were defined: extensive cerebral white matter changes with frontal
      predominance, a periventricular rim with high signal on T1-weighted images and
      low signal on T2-weighted images, abnormalities of basal ganglia and thalami,
      brain stem abnormalities, and contrast enhancement of particular gray and white
      matter structures. Four of the five criteria had to be met for an MR imaging
      based diagnosis. In a retrospective analysis of the MR studies of the 217
      patients, 19 were found who fulfilled these criteria. No other essentially new MR
      abnormalities were found in these patients. In four of the 19 patients,
      subsequent histologic confirmation was obtained. The clinical symptomatology was
      the same in the patients with and without histologic confirmation and correlated
      well with the MR abnormalities. MR abnormalities were in close agreement with the
      known histopathologic findings of Alexander disease. CONCLUSION: The defined
      criteria are sufficient for an in vivo MR imaging diagnosis of Alexander disease;
      only in atypical cases is a brain biopsy still necessary for a definitive
      diagnosis.

PMID- 11237984
TI  - Early-onset combined methylmalonic aciduria and homocystinuria: neuroradiologic
      findings.
AB  - BACKGROUND AND PURPOSE: Combined methylmalonic aciduria and homocystinuria (MMA
      HC) is caused by impaired hepatic conversion of dietary cobalamin to
      methylcobalamin and adenosylcobalamin, resulting in decreased activity of
      methylmalonyl-CoA mutase and methionine synthase. Patients with the early-onset
      variety present within 12 months of age with severe neurologic, hematologic, and
      gastrointestinal abnormalities. We describe the neuroradiologic features of early
      onset MMA-HC and discuss related pathophysiological mechanisms. METHODS: Twelve
      infants with hypotonia, failure to thrive, poor feeding, and hematologic
      abnormalities were diagnosed with MMA-HC on the basis of a typical plasmatic and
      urinary metabolic profile and enzyme activity in fibroblastic cultures.
      Complementation studies were performed in two cases, and yielded a CblC result.
      MR imaging was performed at presentation in four cases and later in the others.
      All patients showed prompt biochemical improvement with intramuscular
      hydroxocobalamin administration, and most had moderate neurologic improvement.
      RESULTS: Diffuse supratentorial white matter edema and dysmyelination was the
      typical MR picture at presentation, whereas white matter bulk loss characterized
      later stages of the disease. Nucleocapsular areas of gliosis were an additional
      finding in one case. One patient had tetraventricular hydrocephalus at
      presentation. CONCLUSION: White matter damage is probably caused by reduced
      methyl group availability and nonphysiological fatty acids toxicity, whereas
      focal gliosis results from homocysteine-induced toxicity to the endothelium.
      Hydrocephalus may result from diffuse intracranial extracerebral arterial
      stiffness, known as reduced arterial pulsation hydrocephalus. MR imaging features
      at presentation and at follow-up are nonspecific.

PMID- 11237985
TI  - Children with macrocrania: clinical and imaging predictors of disorders requiring
      surgery.
AB  - BACKGROUND AND PURPOSE: Macrocrania is a common pediatric clinical condition
      affecting up to 5% of the population. The purpose of this study was to determine
      clinical and imaging predictors that are useful in the differentiation of
      disorders requiring surgical treatment from those that can be treated medically
      in children with macrocrania. METHODS: In a 3-year 7-month retrospective study,
      88 patients (median age, 8 months; interquartile range, 5--13 months) with
      macrocrania and no known underlying neurologic disorder underwent imaging of the
      brain (sonography, n = 36; CT, n = 31; MR imaging = 21). The study was conducted
      in a pediatric tertiary care referral center. Clinical and imaging data were
      correlated to final diagnosis by means of logistic regression and receiver
      operating characteristic curves. RESULTS: Sixteen (18%) of the patients had
      disorders requiring surgery: communicating hydrocephalus, n = 7; noncommunicating
      hydrocephalus, n = 3; hemorrhagic subdural collections, n = 3; neoplasm, n = 1;
      encysted cavum septi pellucidi, n = 1; and vein of Galen malformation, n = 1.
      Clinical predictors of disorders requiring surgery included vomiting (P =.007),
      labor instrumentation (P =.026), developmental delay (P =.008), and abnormal
      neurologic findings (P =.028). Imaging predictors of disorders requiring surgery
      included a focal space-occupying lesion (P <.0001) and moderate-to-severe
      ventriculomegaly (P <.0001). The diagnostic sensitivity of the combination of
      independent clinical and imaging predictors was higher than that of independent
      clinical predictors alone, being 100% (95% confidence interval = 96.9%, 100%) and
      93.8% (95% confidence interval = 88.7%, 98.8%), respectively. A trend indicated
      that the area under the receiver operating characteristic curve for clinical plus
      imaging findings (0.95) was greater than that for clinical findings alone (0.85)
      (P =.09). An increase in the number of clinical and imaging predictors was highly
      correlated with an increased risk of a disorder requiring surgery (P <.0001).
      CONCLUSION: Baseline neuroimaging is indicated for children with macrocrania
      because the combination of clinical and imaging predictors has the best
      diagnostic performance in determining the need for surgical versus nonsurgical
      management.

PMID- 11237986
TI  - Fluoroscopy-guided lumbar puncture: decreased frequency of traumatic tap and
      implications for the assessment of CT-negative acute subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: In patients with suspected subarachnoid hemorrhage (SAH)
      and negative CT findings, the iatrogenic introduction of RBCs into the CSF during
      lumbar puncture may lead to a misdiagnosis. We tested the hypothesis that the
      risk of traumatic lumbar puncture is lower with the fluoroscopy-guided technique
      than with the standard bedside technique. METHODS: Data were collected
      retrospectively from two populations: adult inpatients undergoing standard
      bedside lumbar puncture for any reason and adult patients undergoing fluoroscopy
      guided lumbar puncture for myelography. Patients with SAH and CSF samples with
      significant abnormalities other than erythrocytosis (ie, CSF leukocytosis,
      xanthochromia, or elevated protein) were excluded. In all, 1489 bedside
      procedures and 723 fluoroscopy-guided procedures met the criteria. RESULTS: We
      found a significant difference in the level of iatrogenic CSF erythrocytosis
      produced by the two procedures. Using a cutoff of 1000 cells/mm(3), the frequency
      of traumatic lumbar puncture was 10.1% for bedside lumbar puncture and 3.5% for
      fluoroscopy-guided lumbar puncture. With fluoroscopic guidance, the frequency of
      a traumatic tap varied significantly with the operator, ranging from 0% to 24%.
      CONCLUSION: The use of fluoroscopy-guided lumbar puncture in patients with
      suspected SAH and negative CT findings should reduce the frequency of false
      positive diagnoses of acute SAH as well as the number of unnecessary angiograms
      for patients with suspected SAH but no underlying intracranial vascular
      malformation.

PMID- 11237987
TI  - Spinal cord involvement in primary angiitis of the central nervous system: a
      report of two cases.
AB  - SUMMARY: We report two patients with suspected primary angiitis of the CNS who
      underwent serial contrast-enhanced MR imaging of the spinal cord. MR
      abnormalities were multiple and enhancing, and located within the cervical and
      thoracic cord. Brain MR findings and brain biopsy specimens were positive for
      primary angiitis of the CNS. On follow-up MR studies, obtained after steroid and
      immunosuppressive therapy, a significant decrease in the number and size of the
      enhancing and nonenhancing abnormalities was observed, along with clinical
      improvement. Numerous small and enhancing abnormalities with a primarily
      posterior location, seen at the onset of the disease and resolved on follow-up
      studies, may be considered suggestive of a diagnosis of primary angiitis of the
      CNS.

PMID- 11237992
TI  - Vertebroplasty for osteoporotic compression fracture: effective treatment for a
      neglected disease.

PMID- 11237988
TI  - In re: Amundsen P. Cerebral angiography via the femoral artery with particular
      reference to cerebrovascular disease. Acta Neurol Scand 1967; Suppl. 31:115.

PMID- 11237993
TI  - Toward a better understanding of normal pressure hydrocephalus.

PMID- 11237994
TI  - Nitric oxide production in the hypoxic lung.
AB  - Nitric oxide (NO) is a potent vasodilator and inhibitor of vascular remodeling.
      Reduced NO production has been implicated in the pathophysiology of pulmonary
      hypertension, with endothelial NO synthase (NOS) knockout mice showing an
      increased risk for pulmonary hypertension. Because molecular oxygen (O2) is an
      essential substrate for NO synthesis by the NOSs and biochemical studies using
      purified NOS isoforms have estimated the Michaelis-Menten constant values for O2
      to be in the physiological range, it has been suggested that O2 substrate
      limitation may limit NO production in various pathophysiological conditions
      including hypoxia. This review summarizes numerous studies of the effects of
      acute and chronic hypoxia on NO production in the lungs of humans and animals as
      well as in cultured vascular cells. In addition, the effects of hypoxia on NOS
      expression and posttranslational regulation of NOS activity by other proteins are
      also discussed. Most studies found that hypoxia limits NO synthesis even when NOS
      expression is increased.

PMID- 11237995
TI  - Reactive species and signal transduction.

PMID- 11237996
TI  - Reactive oxygen species stimulate VEGF production from C(2)C(12) skeletal
      myotubes through a PI3K/Akt pathway.
AB  - Vascular endothelial growth factor (VEGF) is a potent angiogenic stimulus, the
      expression of which increases in skeletal muscle after exercise. Because exercise
      is also accompanied by increased intramuscular reactive oxygen species (ROS)
      generation, we tested the hypothesis that ROS stimulate VEGF production from
      skeletal myotubes. Differentiated C(2)C(12) skeletal myotubes exposed to ROS
      producing agents exhibited a concentration-dependent increase in VEGF production,
      whereas undifferentiated myoblasts did not respond to oxidants. Moreover,
      conditioned medium from ROS-treated myotubes increased the bovine lung
      microvascular cell proliferation rate. To study the mechanism(s) involved in the
      stimulation of VEGF production by ROS, myotubes were pretreated with a selective
      phosphatidylinositol 3-kinase (PI3K) inhibitor, LY-294002, before being exposed
      to hydrogen peroxide or pyrogallol. LY-294002 attenuated both Akt phosphorylation
      and VEGF production. In addition, oxidants increased nuclear factor-kappaB
      dependent promoter activity in transiently transfected myotubes; however,
      pretreatment with the pharmacological inhibitor of nuclear factor-kappaB,
      diethyldithiocarbamate, did not affect the oxidant-stimulated VEGF release. We
      conclude that ROS induce VEGF release from myotubes via a PI3K/Akt-dependent
      pathway.

PMID- 11237997
TI  - The stuff of life: an integrated inflammatory response.

PMID- 11237998
TI  - Changes in airway resistance by simultaneous exposure to TNF-alpha and IL-1beta
      in perfused rat lungs.
AB  - Tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta are formed
      simultaneously under inflammatory conditions such as asthma and acute respiratory
      distress syndrome. Here we investigated the effects of TNF-alpha (10 ng/ml)
      and/or IL-1beta (10 ng/ml) in isolated blood-free perfused rat lungs. In lungs
      precontracted with methacholine, IL-1beta alone and IL-1beta/TNF-alpha decreased
      airway resistance 10 min after administration, whereas TNF-alpha alone had no
      effect. In untreated lungs, airway resistance was unaltered by either cytokine
      alone but started to increase 40 min after treatment with both cytokines
      together, indicating bronchoconstriction. The bronchoconstriction was accompanied
      by a steroid-sensitive increase in cyclooxygenase (COX)-2 mRNA expression and
      thromboxane formation. The cytokine-induced bronchoconstriction was blocked by
      the thromboxane receptor antagonist SQ-29548, indomethacin, the selective COX-2
      inhibitor NS-398, and the steroid dexamethasone. We conclude that IL-1beta has an
      early bronchodilatory effect (after 10 min) that is unchanged by TNF-alpha.
      However, at later time points (after 40 min), IL-1beta and TNF-alpha in concert
      cause a COX-2- and thromboxane-dependent bronchoconstriction. Our findings show
      that TNF-alpha and IL-1beta exert complex and time-dependent effects on lung
      functions that cannot be predicted by studying each cytokine alone.

PMID- 11237999
TI  - Loss of liquid from the lung lumen in labor: more than a simple "squeeze".

PMID- 11238000
TI  - Alveolar fluid clearance in late-gestational guinea pigs after labor induction:
      mechanisms and regulation.
AB  - We tested the hypothesis that labor-induced epinephrine release would stimulate
      alveolar fluid clearance in preterm fetuses. Preterm fetuses were obtained by
      cesarean section from timed-pregnant guinea pigs at 61-69 days postconception.
      Fetal guinea pigs were euthanized and placed on continuous positive airway
      pressure oxygenation, and an isosmolar 5% albumin solution was instilled.
      Alveolar fluid clearance was measured over 1 h. The fetal lung began to absorb
      fluid at 64-66 days postconception, and at birth, alveolar fluid clearance
      quadrupled. Baseline alveolar fluid clearance when present was sensitive to
      propranolol inhibition and depended on beta-adrenergic stimulation. Measurements
      of plasma epinephrine in fetal animals confirmed high epinephrine levels in 66-
      to 69-day postconception fetuses. Prenatal alveolar fluid clearance when present
      was highly amiloride sensitive, suggesting that amiloride-sensitive Na+ channels
      were critical. Oxytocin-induced labor initiated an amiloride- and propranolol
      sensitive net alveolar fluid clearance in 61-day-gestation animals. Moreover,
      oxytocin induced significant epinephrine release in all fetuses. These results
      have clinical implications for infants delivered by cesarean section before the
      onset of labor. Use of pharmacological agents to induce labor may reduce the
      occurrence and severity of perinatal respiratory distress.

PMID- 11238001
TI  - The role of p21(CIP1/WAF1) in growth of epithelial cells exposed to hyperoxia.
AB  - Previous studies have shown that hyperoxia inhibits proliferation and increases
      the expression of the tumor suppressor p53 and its downstream target, the cyclin
      dependent kinase inhibitor p21(CIP1/WAF1), which inhibits proliferation in the G1
      phase of the cell cycle. To determine whether growth arrest was mediated through
      activation of the p21-dependent G1 checkpoint, the kinetics of cell cycle
      movement during exposure to 95% O2 were assessed in the Mv1Lu and A549 pulmonary
      adenocarcinoma cell lines. Cell counts, 5-bromo-2'-deoxyuridine incorporation,
      and cell cycle analyses revealed that growth arrest of both cell lines occurred
      in S phase, with A549 cells also showing evidence of a G1 arrest. Hyperoxia
      increased p21 in A549 but not in Mv1Lu cells, consistent with the activation of
      the p21-dependent G1 checkpoint. The ability of p21 to exert the G1 arrest was
      confirmed by showing that hyperoxia inhibited proliferation of HCT 116 colon
      carcinoma cells predominantly in G1, whereas an isogenic line lacking p21
      arrested in S phase. The cell cycle arrest in S phase appears to be a p21
      independent process caused by a gradual reduction in the rate of DNA strand
      elongation. Our data reveal that hyperoxia inhibits proliferation in G1 and S
      phase and demonstrate that p53 and p21 retain their ability to affect G1
      checkpoint control during exposure to elevated O2 levels.

PMID- 11238002
TI  - B-cell isotype control in atopy and asthma assessed with cDNA array technology.
AB  - B-cell isotype switching and the production of IgE is regulated by a variety of
      gene products through different mechanisms. A better understanding of these
      processes has the potential to identify markers of disease and new therapeutic
      targets. The aim of the study was to investigate human B-cell isotype control and
      IgE production in atopy and asthma with cDNA array technology. Eighteen atopic
      asthmatic, eight atopic nonasthmatic, and fourteen healthy control subjects were
      included. Peripheral blood mononuclear cells were separated by gradient
      centrifugation, mRNA was purified, and the reverse-transcribed probes were
      hybridized to cDNA membranes. Group differences were assessed with the Mann
      Whitney U-test. Twenty-three of seventy-eight tested IgE-related genes had
      significantly altered expression in atopy and asthma compared with that in the
      healthy subjects. The differentially expressed genes include surface molecules
      involved in T- and B-cell interaction and activation, cytokines, intracellular
      signaling products, and transcription factors. In conclusion, both atopic
      nonasthmatic and atopic asthmatic individuals had activated proinflammatory
      pathways, a minimal requirement for B-cell isotype switching, and a clear net pro
      IgE cytokine climate.

PMID- 11238003
TI  - NO and reactive oxygen species are involved in biphasic hypoxic vasoconstriction
      of isolated rabbit lungs.
AB  - Hypoxic pulmonary vasoconstriction (HPV) matches lung perfusion with ventilation
      but may also result in chronic pulmonary hypertension. It has not been clarified
      whether acute HPV and the response to prolonged alveolar hypoxia are triggered by
      identical mechanisms. We characterized the vascular response to sustained hypoxic
      ventilation (3% O(2) for 120-180 min) in isolated rabbit lungs. Hypoxia provoked
      a biphasic increase in pulmonary arterial pressure (PAP). Persistent PAP
      elevation was observed after termination of hypoxia. Total blockage of lung
      nitric oxide (NO) formation by N(G)-monomethyl-L-arginine caused a two- to
      threefold amplification of acute HPV, the sustained pressor response, and the
      loss of posthypoxic relaxation. This amplification was only moderate when NO
      formation was partially blocked by the inducible NO synthase inhibitor S
      methylisothiourea. The superoxide scavenger nitro blue tetrazolium and the
      superoxide dismutase inhibitor triethylenetetramine reduced the initial
      vasoconstrictor response, the prolonged PAP increase, and the loss of posthypoxic
      vasorelaxation to a similar extent. The NAD(P)H oxidase inhibitor
      diphenyleneiodonium nearly fully blocked the late vascular responses to hypoxia
      in a dose that effected a decrease to half of the acute HPV. In conclusion, as
      similarly suggested for acute HPV, lung NO synthesis and the superoxide-hydrogen
      peroxide axis appear to be implicated in the prolonged pressor response and the
      posthypoxic loss of vasorelaxation in perfused rabbit lungs undergoing 2-3 h of
      hypoxic ventilation.

PMID- 11238004
TI  - Expression of highly selective sodium channels in alveolar type II cells is
      determined by culture conditions.
AB  - Alveolar fluid clearance in the developing and mature lungs is believed to be
      mediated by some form of epithelial Na channels (ENaC). However, single-channel
      studies using isolated alveolar type II (ATII) cells have failed to demonstrate
      consistently the presence of highly selective Na+ channels that would be expected
      from ENaC expression. We postulated that in vitro culture conditions might be
      responsible for alterations in the biophysical properties of Na+ conductances
      observed in cultured ATII cells. When ATII cells were grown on glass plates
      submerged in media that lacked steroids, the predominant channel was a 21-pS
      nonselective cation channel (NSC) with a Na+-to-K+ selectivity of 1; however,
      when grown on permeable supports in the presence of steroids and air interface,
      the predominant channel was a low-conductance (6.6 +/- 3.4 pS, n = 94), highly
      Na+-selective channel (HSC) with a P(Na)/P(K) >80 that is inhibited by
      submicromolar concentrations of amiloride (K(0.5) = 37 nM) and is similar in
      biophysical properties to ENaC channels described in other epithelia. To
      establish the relationship of this HSC channel to the cloned ENaC, we employed
      antisense oligonucleotide methods to inhibit the individual subunit proteins of
      ENaC (alpha, beta, and gamma) and used patch-clamp techniques to determine the
      density of this channel in apical membrane patches of ATII cells. Overnight
      treatment of cells with antisense oligonucleotides to any of the three subunits
      of ENaC resulted in a significant decrease in the density of HSC channels in the
      apical membrane cell-attached patches. Taken together, these results show that
      when grown on permeable supports in the presence of steroids and air interface,
      the predominant channels expressed in ATII cells have single-channel
      characteristics resembling channels that are associated with the coexpression of
      the three cloned ENaC subunits alpha-, beta-, and gamma-ENaC.

PMID- 11238005
TI  - Effect of endothelin antagonism on the production of cytokines in eosinophilic
      airway inflammation.
AB  - Endothelin (ET)-1 has been launched as an important mediator in bronchial asthma,
      which is an eosinophilic airway inflammation. However, the interplay between ET-1
      and other proinflammatory mediators during the development of airway inflammation
      has not been elucidated. We wanted to study 1) whether the production of ET-1
      precedes the production of other proinflammatory mediators and 2) whether ET-1
      stimulates the production of these mediators within the airways. These hypotheses
      were studied during the development of an eosinophilic airway inflammation in
      rats. The increase in ET-1 mRNA level in lung tissue preceded the increase in
      mRNA levels of tumor necrosis factor-alpha, interleukin (IL)-1beta, and IL-8.
      Treatment of the animals with the ET receptor antagonist bosentan resulted in a
      substantial decrease in the concentrations of tumor necrosis factor-alpha, IL-4,
      IL-1beta, interferon-gamma, and ET-1 in bronchoalveolar lavage fluid. In
      conclusion, the synthesis of ET-1 as measured by increased mRNA level precedes
      the synthesis of other proinflammatory cytokines of importance for the
      development of an eosinophilic airway inflammation, and ET antagonism inhibits
      the production of these mediators within the airways. Whether treatment with ET
      antagonists will prove beneficial for patients with eosinophilic airway
      inflammations like bronchial asthma is not yet known.

PMID- 11238006
TI  - Excitation-contraction coupling in pulmonary vascular smooth muscle involves
      tyrosine kinase and Rho kinase.
AB  - We investigated the mechanisms that underlie the responses to norepinephrine (NE)
      and thromboxane (Tx) A(2) (TxA2) in the canine pulmonary vasculature with fura 2
      fluorimetric, intracellular microelectrode, and force transduction techniques.
      KCl, caffeine, and cyclopiazonic acid elevated intracellular Ca2+ concentration
      levels and tone, indicating that Ca2+ mobilization is sufficient to produce
      contraction. However, contractions evoked by NE or the TxA2 mimetic U-46619 were
      unaffected by nifedipine or by omitting external Ca2+ and were reduced only
      partially by depleting the internal Ca2+ store; furthermore, NE-evoked
      depolarization was subthreshold for voltage-dependent Ca2+ currents. Agonist
      evoked contractions were insensitive to inhibitors of protein kinase C
      (calphostin C and chelerythrine), mitogen-activated protein kinase kinase (PD
      98059), and p38 kinase (SB-203580) but were abolished by the tyrosine kinase
      inhibitor genistein and the Rho kinase inhibitor Y-27632. We conclude that,
      although Ca2+ influx and Ca2+ release are sufficient for contraction, they are
      not necessary for adrenergic or TxA2 contractions. Instead, excitation
      contraction coupling involves the activation of tyrosine kinase and Rho kinase,
      leading to enhanced Ca2+ sensitivity of the contractile apparatus.

PMID- 11238007
TI  - IL-1beta enhances beta2-adrenergic receptor expression in human airway epithelial
      cells by activating PKC.
AB  - Protein kinase C (PKC)-activated signal transduction pathways regulate cell
      growth and differentiation in many cell types. We have observed that interleukin
      (IL)-1beta upregulates beta2-adrenergic receptor (beta2-AR) density and beta2-AR
      mRNA in human airway epithelial cells (e.g., BEAS-2B). We therefore tested the
      hypothesis that PKC-activated pathways mediate IL-1beta-induced beta-AR
      upregulation. The role of PKC was assessed from the effects of 1) the PKC
      activator phorbol 12-myristate 13-acetate (PMA) on beta-AR density, 2) selective
      PKC inhibitors (calphostin C and Ro-31-8220) on beta-AR density, and 3) IL-1beta
      treatment on the cellular distribution of PKC isozymes. Recombinant human IL
      1beta (0.2 nM for 18 h) increased beta-AR density to 213% of control values (P <
      0.001). PMA (1 microM for 18 h) increased beta-AR density to 225% of control
      values (P < 0.005), whereas Ro-31-8220 and calphostin C inhibited the IL-1beta
      induced upregulation of beta-AR in dose-dependent fashion. PKC isozymes detected
      by Western blotting included alpha, betaII, epsilon, mu, zeta, and lambda/iota.
      IL-1beta increased PKC-mu immunoreactivity in the membrane fraction and had no
      effect on the distribution of the other PKC isozymes identified. These data
      indicate that IL-1beta-induced beta-AR upregulation is mimicked by PKC activators
      and blocked by PKC inhibitors and appears to involve selective activation of the
      PKC-mu isozyme. We conclude that signal transduction pathways activated by PKC-mu
      upregulate beta2-AR expression in human airway epithelial cells.

PMID- 11238008
TI  - Extracellular matrix fibronectin alters connexin43 expression by alveolar
      epithelial cells.
AB  - Alveolar type II epithelial cells undergo phenotypic changes and establish gap
      junction intercellular communication as they reach confluence in primary culture.
      The pattern of gap junction protein (connexin) expression changes in parallel.
      Although connexin (Cx)43 mRNA and protein increase significantly by culture day
      2, Cx26 and Cx32 expression decline. Along with increasing Cx43 expression, the
      cells assemble fibronectin derived both from serum in the culture medium and from
      de novo synthesis into the extracellular matrix (ECM). The present studies
      indicate that this ECM regulates Cx43 expression. Culture of type II cells in
      DMEM containing 8-10% fetal bovine serum (FBS) promotes assembly of a fibronectin
      rich ECM that stimulates expression of both Cx43 mRNA and protein. Although Cx43
      protein expression increased in response to FBS in a dose-dependent manner,
      fibronectin also elevated Cx43 protein in the absence of FBS. Anti-fibronectin
      antibody significantly reduced the serum-dependent increase in Cx43 expression.
      These results support the premise that fibronectin in the ECM contributes to the
      regulation of Cx43 expression by alveolar epithelial cells in primary culture.

PMID- 11238009
TI  - Exogenous surfactant changes the phenotype of alveolar macrophages in mice.
AB  - Alveolar macrophages are essential for the maintenance of surfactant homeostasis.
      We asked whether surfactant treatment would change alveolar macrophage number and
      whether the alveolar macrophage phenotype would become activated or apoptotic
      when challenged in vivo with exogenous surfactant. Surfactant pool size in mice
      was increased by repetitive surfactant treatments containing 120 mg/kg (110
      micromol/kg) saturated phosphatidylcholine. The number of alveolar macrophages
      recovered by alveolar lavage decreased after the first dose by 49% and slightly
      increased after the second and third doses. Up to 28.5% of the macrophages became
      large and foamy, and their appearance normalized within 12 h. Surfactant
      treatment did not increase the percent of apoptotic or necrotic cells. The
      alveolar macrophages were not activated as indicated by no change in expression
      of CD14, CD16, CD54, CD95, and scavenger receptor class A types I and II after
      surfactant treatment. Surfactant treatment in healthy mice transiently changed
      the phenotype of alveolar macrophages to large and foamy without indications of
      changes in the surface markers characteristic of activation.

PMID- 11238010
TI  - Differential expression of forkhead box transcription factors following butylated
      hydroxytoluene lung injury.
AB  - The forkhead box (Fox) proteins are a growing family of transcription factors
      that have important roles in cellular proliferation and differentiation and in
      organ morphogenesis. The Fox family members hepatocyte nuclear factor (HNF)-3beta
      (Foxa2) and HNF-3/forkhead homolog (HFH)-8 (FREAC-1, Foxf1) are expressed in
      adult pulmonary epithelial and mesenchymal cells, respectively, but these cells
      display only low expression levels of the proliferation-specific HFH-11B gene
      (Trident, Foxm1b). The regulation of these Fox transcription factors in response
      to acute lung injury, however, has yet to be determined. We report here on the
      use of butylated hydroxytoluene (BHT)-mediated lung injury to demonstrate that
      HFH-11 protein and RNA levels were markedly increased throughout the period of
      lung repair. The maximum levels of HFH-11 were observed by day 2 following BHT
      injury when both bronchiolar and alveolar epithelial cells were undergoing
      extensive proliferation. Although BHT lung injury did not alter epithelial cell
      expression of HNF-3beta, a 65% reduction in HFH-8 mRNA levels was observed during
      the period of mesenchymal cell proliferation. HFH-8-expressing cells were
      colocalized with platelet endothelial cell adhesion molecule-1-positive alveolar
      endothelial cells and with alpha-smooth muscle actin-positive peribronchiolar
      smooth muscle cells.

PMID- 11238012
TI  - A murine model of smoke inhalation.
AB  - The United States has one of the world's largest per capita fire death rates.
      House fires alone kill >9,000 Americans annually, and smoke inhalation is the
      leading cause of mortality from structural fires. Animal models are needed to
      develop therapies to combat this problem. We have developed a murine model of
      smoke inhalation through the design, construction, and use of a controlled
      environment smoke chamber. There is a direct relationship between the quantity of
      wood combusted and mortality in mice. As with human victims, the primary cause of
      death from smoke inhalation is an elevated blood carboxyhemoglobin level. Lethal
      (78%) and sublethal (50%) carboxyhemoglobin levels were obtained in mice
      subjected to varying amounts of smoke. Mice exposed to wood smoke demonstrated
      more dramatic pathology than mice exposed to cotton or polyurethane smoke. A CD-1
      model of wood smoke exposure was developed, demonstrating type II cell
      hypertrophy, cytoplasmic blebbing, cytoplasmic vacuolization, sloughing,
      hemorrhage, edema, macrophage infiltration, and lymphocyte infiltration. The
      bronchoalveolar lavage fluid of smoke-exposed mice demonstrated a significant
      increase in total cell counts compared with those in control mice. These findings
      are comparable to the lung tissue response observed in human victims of smoke
      inhalation.

PMID- 11238011
TI  - FGF-10 disrupts lung morphogenesis and causes pulmonary adenomas in vivo.
AB  - Transgenic mice in which fibroblast growth factor (FGF)-10 was expressed in the
      lungs of fetal and postnatal mice were generated with a doxycycline-inducible
      system controlled by surfactant protein (SP) C or Clara cell secretory protein
      (CCSP) promoter elements. Expression of FGF-10 mRNA in the fetal lung caused
      adenomatous malformations, perturbed branching morphogenesis, and caused
      respiratory failure at birth. When expressed after birth, FGF-10 caused
      multifocal pulmonary tumors. FGF-10-induced tumors were highly differentiated
      papillary and lepidic pulmonary adenomas. Epithelial cells lining the tumors
      stained intensely for thyroid transcription factor (TTF)-1 and SP-C but not CCSP,
      indicating that FGF-10 enhanced differentiation of cells to a peripheral alveolar
      type II cell phenotype. Withdrawal from doxycycline caused rapid regression of
      the tumors associated with rapid loss of the differentiation markers TTF-1, SP-B,
      and proSP-C. FGF-10 disrupted lung morphogenesis and induced multifocal pulmonary
      tumors in vivo and caused reversible type II cell differentiation of the
      respiratory epithelium.

PMID- 11238013
TI  - Cell-specific and developmental regulation of rabbit surfactant protein B
      promoter in transgenic mice.
AB  - Surfactant protein B (SP-B) is expressed tissue specifically in the lung and is
      developmentally regulated. To identify genomic regions that control SP-B
      expression, we analyzed SP-B promoter activity in transgenic mice containing
      rabbit SP-B 5'-flanking DNA fragments linked to the chloramphenicol
      acetyltransferase (CAT) reporter gene. Results showed that whereas the -2,176/+39
      bp fragment failed to express CAT, shorter fragments of -730/+39 and -236/+39 bp
      expressed CAT tissue specifically in the lung. Further deletion of 5'-flanking
      DNA to -136 bp resulted in no expression of CAT. Immunostaining demonstrated that
      both -730/+39- and -236/+39-bp regions expressed CAT specifically in alveolar
      type II and Clara cells. The -236/+39-bp region expressed CAT at a significantly
      lower level than the -730/+39-bp region. CAT expression in mice containing the 
      730/+39-bp region was detected in embryonic day 14 lung and attained maximum
      levels in day 18 lung, indicating that the developmental expression of CAT was
      similar to that of SP-B. These data show that the DNA elements necessary for cell
      type-specific expression are located within -236/+39 bp of the SP-B gene.
      Additionally, these data suggest that the -2,176/-730- and -730/-236-bp regions
      contain the DNA elements that repress and enhance SP-B gene transcription,
      respectively.

PMID- 11238014
TI  - Permeability of endothelial monolayers to albumin is increased by bradykinin and
      inhibited by prostaglandins.
AB  - Using monolayers of bovine aortic endothelial cells (BAEC) in modified Boyden
      chambers, we examined the role of prostaglandins (PGs) in the bradykinin (BK)
      induced increase of albumin permeability. BK induced a concentration-dependent
      increase of the permeability of BAEC, which reached 49.9 +/- 1% at the
      concentration of 10(-8) M. Two inhibitors of the prostaglandin G/H synthase,
      indomethacin (2.88 microM) and ibuprofen (10 microM), potentiated BK-induced
      permeability 1.8- and 3.9-fold, respectively. Exogenously administered PGE2 and
      iloprost, a stable analog of prostacyclin, attenuated the effect of BK in a
      concentration-dependent manner. Butaprost equally reduced the effect of BK,
      suggesting the participation of the EP2 receptor in this phenomenon. However, the
      EP4-selective antagonist AH-23848 did not significantly inhibit the protective
      effect of PGE2. The inhibitory effect of PGE2 was reversed by the adenylate
      cyclase inhibitor MDL-12330A (10 microM). These results suggest that BK-induced
      increase of permeability of BAEC monolayer to (125)I-labeled albumin is
      negatively regulated by PGs. This postulated autocrine activity of PGs may
      involve an increase in the intracellular level of cAMP.

PMID- 11238015
TI  - Differential regulation of Cl- transport proteins by PKC in Calu-3 cells.
AB  - Cl- transport proteins expressed in a Calu-3 airway epithelial cell line were
      differentiated by function and regulation by protein kinase C (PKC) isotypes.
      mRNA expression of Cl- transporters was semiquantitated by RT-PCR after
      transfection with a sense or antisense oligonucleotide to the PKC isotypes that
      modulate the activity of the cystic fibrosis transmembrane conductance regulator
      [CFTR (PKC-epsilon)] or of the Na/K/2Cl (NKCC1) cotransporter (PKC-delta).
      Expression of NKCC1 and CFTR mRNAs and proteins was independent of antisense
      oligonucleotide treatment. Transport function was measured in cell monolayers
      grown on a plastic surface or on filter inserts. With both culture methods, the
      antisense oligonucleotide to PKC-epsilon decreased the amount of PKC-epsilon and
      reduced cAMP-dependent activation of CFTR but not alpha(1)-adrenergic activation
      of NKCC1. The antisense oligonucleotide to PKC-delta did not affect CFTR function
      but did block alpha(1)-adrenergic activation of NKCC1 and reduce PKC-delta mass.
      These results provide the first evidence for mRNA and protein expression of NKCC1
      in Calu-3 cells and establish the differential regulation of CFTR and NKCC1
      function by specific PKC isotypes at a site distal to mRNA expression and
      translation in airway epithelial cells.

PMID- 11238017
TI  - Reduction of BCNU toxicity to lung cells by high-level expression of O(6)
      methylguanine-DNA methyltransferase.
AB  - 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) is an important cause of pulmonary
      toxicity. BCNU alkylates DNA at the O(6) position of guanine. O(6)-methylguanine
      DNA methyltransferase (MGMT) is a DNA repair protein that removes alkyl groups
      from the O(6) position of guanine. To determine whether overexpression of MGMT in
      a lung cell reduces BCNU toxicity, the MGMT gene was transfected into A549 cells,
      a lung epithelial cell line. Transfected A549 cell populations demonstrated high
      levels of MGMT RNA, MGMT protein, and DNA repair activity. The overexpression of
      MGMT in lung epithelial cells provided protection from the cytotoxic effects of
      BCNU. Control A549 cells incubated with 100 microM BCNU had a cell survival rate
      of 12.5 +/- 1.2%; however, A549 cells overexpressing MGMT had a survival rate of
      71.8 +/- 2.7% (P < 0.001). We also demonstrated successful transfection of MGMT
      into human pulmonary artery endothelial cells and a primary culture of rat type
      II alveolar epithelial cells with overexpression of MGMT, resulting in
      significant protection from BCNU toxicity. These data suggest that overexpression
      of DNA repair proteins such as MGMT in lung cells may protect the lung cells from
      cytotoxic effects of cancer chemotherapy drugs such as BCNU.

PMID- 11238016
TI  - Lysosomal-type PLA2 and turnover of alveolar DPPC.
AB  - This study evaluated the role of a lysosomal-type phospholipase A2 (aiPLA(2)) in
      the degradation of internalized dipalmitoylphosphatidylcholine (DPPC) and in
      phospholipid synthesis by the rat lung. Uptake and degradation of DPPC were
      measured in isolated perfused rat lungs over 3 h following endotracheal
      instillation of [(3)H]DPPC in mixed unilamellar liposomes plus or minus MJ33, a
      specific inhibitor of lung aiPLA(2). Uptake of DPPC was calculated from total
      tissue-associated radiolabel, and degradation was calculated from the sum of
      radiolabel in degradation products. Both uptake and degradation were markedly
      stimulated by addition of 8-bromo-cAMP to the perfusate. MJ33 had no effect on
      DPPC uptake but decreased DPPC degradation at 3 h by approximately 40-50%. The
      effect of MJ33 on lung synthesis of DPPC was evaluated with intact rats over a 12
      to 24-h period following intravenous injection of radiolabeled palmitate and
      choline. MJ33 treatment decreased palmitate incorporation into disaturated
      phosphatidylcholine of lamellar bodies and surfactant by approximately 65% at 24
      h but had no effect on choline incorporation. This result is compatible with
      inhibition of the deacylation/reacylation pathway for DPPC synthesis. These
      results obtained with intact rat lungs indicate that aiPLA(2) is a major enzyme
      for degradation of internalized DPPC and also has an important role in DPPC
      synthesis.

PMID- 11238019
TI  - Inhibition of LPS-induced airway hyperresponsiveness and airway inflammation by
      LPS antagonists.
AB  - To determine whether the inflammatory effects of inhaled endotoxin could be
      prevented, we pretreated mice with synthetic competitive antagonists (975, 1044,
      and 1287) for lipopolysaccharide (LPS) before a LPS inhalation challenge. In
      preliminary studies, we found that these LPS antagonists did not act as agonists
      in vitro (THP-1 cells) or in vivo (after intratracheal instillation of 10 microg)
      and that these compounds (at least 1 microg/ml) effectively antagonized the
      release of tumor necrosis factor-alpha by LPS-stimulated THP-1 cells.
      Pretreatment of mice with 10 microg of either 1044 or 1287 resulted in a decrease
      in the LPS-induced airway hyperreactivity. Moreover, pretreatment of mice with 10
      microg of 975, 1044, or 1287 resulted in significant reductions in LPS-induced
      lung lavage fluid concentrations of total cells, neutrophils, and specific
      proinflammatory cytokines compared with mice pretreated with sterile saline.
      Using residual oil fly ash to induce airway inflammation, we found that the
      action of the LPS antagonists was specific to LPS-induced airway disease. These
      results suggest that LPS antagonists may be an effective and potentially safe
      treatment for endotoxin-induced airway disease.

PMID- 11238018
TI  - Role of LPS-induced microfilament depolymerization in MIP-2 production from rat
      pneumocytes.
AB  - We have previously demonstrated that lipopolysaccharide (LPS) induces production
      of macrophage inflammatory protein-2 (MIP-2), a C-X-C chemokine for neutrophil
      recruitment and activation, in primary cultured rat lung alveolar epithelial
      cells. We have also demonstrated that LPS depolymerizes microfilaments in rat
      alveolar epithelial cells. To determine whether the polymerization status of
      microfilaments affects LPS-induced MIP-2 production, we treated rat alveolar
      epithelial cells with cytochalasin D (CytoD), a microfilament-disrupting agent,
      before and during LPS stimulation. A lower concentration (0.1 microM) of CytoD
      inhibited LPS-induced MIP-2 production without affecting microfilament
      polymerization. In contrast, LPS-induced MIP-2 production was enhanced by a
      higher concentration (10 microM) of CytoD, which disrupted the filamentous
      structure of actin. Jasplakinolide (1 nM to 1 microM), a polymerizing agent for
      microfilaments, decreased LPS-induced MIP-2 secretion. Jasplakinolide (1 microM)
      also blocked LPS-induced depolymerization of microfilaments. These results
      suggest that, in alveolar epithelial cells, LPS-induced MIP-2 production is at
      least partially regulated by microfilament depolymerization.

PMID- 11238020
TI  - Glutamine protects mitochondrial structure and function in oxygen toxicity.
AB  - Glutamine is an important mitochondrial substrate implicated in the protection of
      cells from oxidant injury, but the mechanisms of its action are incompletely
      understood. Human pulmonary epithelial-like (A549) cells were exposed to 95% O2
      for 4 days in the absence and presence of glutamine. Cell proliferation in
      normoxia was dependent on glutamine, and glutamine deprivation markedly
      accelerated cell death in hyperoxia. Glutamine significantly increased cellular
      ATP levels in normoxia and prevented the loss of ATP in hyperoxia seen in
      glutamine-deprived cells. Mitochondrial membrane potential as assessed by flow
      cytometry with chloromethyltetramethylrosamine was increased by glutamine in
      hyperoxia-exposed A549 cells, and a glutamine dose-dependent increase in
      mitochondrial membrane potential was detected. Glutamine-supplemented, hyperoxia
      exposed cells had a higher O2 consumption rate and GSH content. Electron and
      fluorescence microscopy revealed that, in hyperoxia, glutamine protected cellular
      structures, especially mitochondria, from damage. In hyperoxia, activity of the
      tricarboxylic acid cycle enzyme alpha-ketoglutarate dehydrogenase was partially
      protected by its indirect substrate, glutamine, indicating a mechanism of
      mitochondrial protection.

PMID- 11238021
TI  - Conebulization of surfactant and urokinase restores gas exchange in perfused
      lungs with alveolar fibrin formation.
AB  - Alveolar fibrin generation has been suggested to possess strong surfactant
      inhibitory potency. In perfused rabbit lungs, fibrin formation in the alveolar
      space was induced by sequential ultrasonic aerosolization of fibrinogen and
      thrombin, and the efficacy of rescue administration of surfactant and urokinase
      was investigated. Ventilation-perfusion (VA/Q) distribution was assessed by the
      multiple inert gas elimination technique. Aerosolization of fibrinogen
      (approximately 20 mg/kg body wt) increased shunt flow to approximately 7%.
      Sequential nebulization of fibrinogen and thrombin (1.3 U/kg body wt) caused
      alveolar fibrin deposition, documented immunohistologically, and provoked marked
      shunt flow, progressing to approximately 22% at the end of the experiments. The
      hemodynamics were virtually unchanged. Rescue aerosolization of natural bovine
      surfactant (15 mg/kg body wt) or urokinase-type plasminogen activator (4,500 U/kg
      body wt), undertaken after fibrin formation, improved gas exchange but
      progressive shunt flow still occurred (efficacy, surfactant > urokinase). In
      contrast, conebulization of surfactant and urokinase reversed shunt flow to
      approximately 7%, with an increased appearance of normal VA/Q matching. We
      conclude that alveolar fibrin formation is a potent surfactant-inhibitory
      mechanism in intact lungs, provoking severe VA/Q mismatch with a predominance of
      shunt flow, and that rescue aerosolization of surfactant plus urokinase may offer
      restoration of gas exchange under these conditions.

PMID- 11238022
TI  - Chronic hypoxia decreases K(V) channel expression and function in pulmonary
      artery myocytes.
AB  - Activity of voltage-gated K+ (KV) channels regulates membrane potential (E(m))
      and cytosolic free Ca2+ concentration ([Ca2+](cyt)). A rise in ([Ca2+](cyt))in
      pulmonary artery (PA) smooth muscle cells (SMCs) triggers pulmonary
      vasoconstriction and stimulates PASMC proliferation. Chronic hypoxia (PO(2) 30-35
      mmHg for 60-72 h) decreased mRNA expression of KV channel alpha-subunits (Kv1.1,
      Kv1.5, Kv2.1, Kv4.3, and Kv9.3) in PASMCs but not in mesenteric artery (MA) SMCs.
      Consistently, chronic hypoxia attenuated protein expression of Kv1.1, Kv1.5, and
      Kv2.1; reduced KV current [I(KV)]; caused E(m) depolarization; and increased
      ([Ca2+](cyt)) in PASMCs but negligibly affected KV channel expression, increased
      I(KV), and induced hyperpolarization in MASMCs. These results demonstrate that
      chronic hypoxia selectively downregulates KV channel expression, reduces I(KV),
      and induces E(m) depolarization in PASMCs. The subsequent rise in ([Ca2+](cyt))
      plays a critical role in the development of pulmonary vasoconstriction and medial
      hypertrophy. The divergent effects of hypoxia on KV channel alpha-subunit mRNA
      expression in PASMCs and MASMCs may result from different mechanisms involved in
      the regulation of KV channel gene expression.

PMID- 11238023
TI  - Blockade of CD49d inhibits allergic airway pathologies independent of effects on
      leukocyte recruitment.
AB  - Lymphocyte and/or eosinophil recruitment is dependent on the sequential
      interactions between adhesion molecules expressed on activated endothelial cells
      and both leukocyte subtypes. Endothelial P- and E-selectins mediate tethering and
      rolling of leukocytes through interactions with P-selectin glycoprotein ligand-1
      (PSGL-1), and diapedesis subsequently occurs by engagement of endothelial
      vascular cell adhesion molecule-1 and CD49d (alpha(4)-integrins). The anti
      inflammatory potential of interfering with these adhesive interactions was
      assessed with an ovalbumin challenge mouse model of asthma. Administration of a
      soluble form of PSGL-1 reduced eosinophils (80%) and lymphocytes (50%) in
      bronchoalveolar lavage fluid without affecting epithelial changes or airway
      hyperreactivity (AHR). In contrast, although administration of anti-CD49d
      monoclonal antibodies (PS/2) resulted in similar reductions in eosinophils (75%)
      and lymphocytes (50%), PS/2 reduced and abolished mucous cell metaplasia and AHR,
      respectively. Administration of both PSGL-1 and PS/2 had the additive effect of
      eliminating eosinophils from the airways (96% decrease), with few or no
      additional reductions (relative to PS/2 administration alone) in lymphocyte
      recruitment, mucous cell metaplasia, or AHR. These data show that eosinophils and
      lymphocytes differentially utilize adhesive interactions during recruitment and
      that the inhibition of AHR is independent of this recruitment.

PMID- 11238026
TI  - Glomeruloid microvascular proliferation orchestrated by VPF/VEGF: a new world of
      angiogenesis research.

PMID- 11238028
TI  - A comparative study of the expression of cytotoxic proteins in allergic contact
      dermatitis and psoriasis: spongiotic skin lesions in allergic contact dermatitis
      are highly infiltrated by T cells expressing perforin and granzyme B.
AB  - Recent reports indicate that cytotoxic T cells are critically involved in contact
      hypersensitivity reactions in animals. In this study we sought to investigate the
      in vivo expression of cytotoxic granule proteins in the elicitation phase of
      allergic contact dermatitis in humans. Skin biopsy specimens were obtained from
      patients with allergic contact dermatitis (n = 8) and psoriasis (n = 6) and from
      controls with normal skin (n = 6). Expression of perforin and granzyme B was
      investigated by in situ hybridization and immunohistochemistry. In contrast to
      normal skin and psoriasis, a significant enhancement of perforin and granzyme B
      gene expression and immunoreactivity was observed in the mononuclear cell
      infiltrate of allergic contact dermatitis. Immunoreactivity for perforin and
      granzyme B was mainly found in the cytoplasm of lymphocytic cells, which were
      located in the dense perivascular infiltrate as well as at sites of marked
      spongiosis in the epidermis. Double immunostaining revealed that both CD4+ and
      CD8+ T cells are capable of expressing perforin and granzyme B. In conclusion,
      our data suggest that T-cell-mediated mechanisms involving cytotoxic granule
      proteins may elicit epidermal cell injury in vivo and thereby strongly contribute
      to the development of allergic contact dermatitis in humans.

PMID- 11238029
TI  - Selective expression of murine prostate stem cell antigen in fetal and adult
      tissues and the transgenic adenocarcinoma of the mouse prostate model of prostate
      carcinogenesis.
AB  - Prostate stem cell antigen (PSCA) is a GPI-anchored membrane protein whose
      expression is reportedly up-regulated in a majority of human prostate cancers,
      including advanced stages and metastases. In this study, we investigate the
      expression pattern of the murine orthologue of PSCA by in situ hybridization in
      fetal and adult mouse tissues. Murine PSCA is expressed during fetal development
      in the urogenital sinus, skin, and gastrointestinal tract. The expression in
      these tissues is restricted to the most superficial cell layer. In the adult
      mouse, expression is highest in the mucosal lining of the urinary tract. In the
      normal adult prostate, expression of PSCA is detected exclusively in the
      secretory epithelium. Examination of PSCA during carcinogenesis of the murine
      prostate in the transgenic adenocarcinoma of the mouse prostate model showed a
      markedly increased expression in areas of neoplasia. The transgenic
      adenocarcinoma of the mouse prostate model may represent a valuable model for the
      study of PSCA as a potential target for immunotherapy of prostate cancer, despite
      potential differences in the pattern of expression between mice and humans.

PMID- 11238027
TI  - Alzheimer's disease in man and transgenic mice: females at higher risk.

PMID- 11238030
TI  - Expression of the intermediate filament nestin in gastrointestinal stromal tumors
      and interstitial cells of Cajal.
AB  - It has recently been proposed that gastrointestinal stromal tumors (GISTs)
      originate from stem cells that differentiate toward a phenotype of interstitial
      cells of Cajal (ICCs). Nestin is a newly identified intermediate filament
      protein, and is predominantly expressed in immature cells, such as
      neuroectodermal stem cells and skeletal muscle progenitor cells, and tumors
      originating from these cells. In this study, we examined, using
      immunohistochemistry, the nestin expression in GISTs and ICCs to clarify the
      origin of GISTs. Strong immunoreactivity for nestin was observed in all 18 GISTs,
      and its expression was confirmed by Western blot and Northern blot analyses. In
      contrast, three leiomyomas and a schwannoma that developed in the
      gastrointestinal tract showed no apparent immunoreactivity for nestin. Among 17
      mesenchymal tumors (seven leiomyosarcomas, five malignant peripheral nerve sheath
      tumors, and five fibrosarcomas) that occurred in sites other than the
      gastrointestinal tract, only two malignant peripheral nerve sheath tumors were
      moderately immunoreactive for nestin. Furthermore, with fluorescence double
      immunostaining of the normal small intestine, nestin expression was demonstrated
      in ICCs. These results show that nestin may be a useful marker for diagnosis of
      GISTs, and support the current hypothesis that GISTs are tumors of stem cells
      that differentiate toward an ICC phenotype.

PMID- 11238031
TI  - Expression of scavenger receptor class B, type I, by astrocytes and vascular
      smooth muscle cells in normal adult mouse and human brain and in Alzheimer's
      disease brain.
AB  - In Alzheimer's disease (AD), fibrillar beta-amyloid protein (fAbeta) accumulates
      in the walls of cerebral vessels associated with vascular smooth muscle cells
      (SMCs), endothelium, and pericytes, and with microglia and astrocytes in plaques
      in the brain parenchyma. Scavenger receptor class A (SR-A) and class B, type I
      (SR-BI) mediate binding and ingestion of fAbeta by cultured human fetal
      microglia, microglia from newborn mice, and by cultured SMCs. Our findings that
      SR-BI participates in the adhesion of cultured microglia from newborn SR-A knock
      out mice to fAbeta-coated surfaces, and that microglia secrete reactive oxygen
      species when they adhere to these surfaces prompted us to explore expression of
      SR-BI in vivo. We report here that astrocytes and SMCs in normal adult mouse and
      human brains and in AD brains express SR-BI. In contrast, microglia in normal
      adult mouse and human brains and in AD brains do not express SR-BI. These
      findings indicate that SR-BI may mediate interactions between astrocytes or SMCs
      and fAbeta, but not of microglia and fAbeta, in AD, and that expression of SR-BI
      by rodent microglia is developmentally regulated. They suggest that SR-BI
      expression also is developmentally regulated in human microglia.

PMID- 11238032
TI  - Down-regulation of caveolin-1, a candidate tumor suppressor gene, in sarcomas.
AB  - Caveolae are plasma membrane microdomains that have been implicated in the
      regulation of several intracellular signaling pathways. Previous studies suggest
      that caveolin-1, the main structural protein of caveolae, could function as a
      tumor suppressor. Caveolin-1 is highly expressed in terminally differentiated
      mesenchymal cells including adipocytes, endothelial cells, and smooth muscle
      cells. To study whether caveolin-1 is a possible tumor suppressor in human
      mesenchymal tumors, we have analyzed the expression using immunohistochemistry in
      normal mesenchymal tissues, 22 benign and 79 malignant mesenchymal tumors.
      Caveolin-1 was found to be expressed in fibromatoses, leiomyomas, hemangiomas,
      and lipomas at high levels comparable to normal mesenchymal tissues. The
      expression of caveolin-1 was slightly reduced in four of six well-differentiated
      liposarcomas and strongly reduced or lost in three of three fibrosarcomas, 17 of
      20 leiomyosarcomas, 16 of 16 myxoid/round cell/pleomorphic liposarcomas, five of
      eight angiosarcomas, 15 of 18 malignant fibrous histiocytomas, and eight of eight
      synovial sarcomas. The immunohistochemical findings were confirmed by Western
      blot analysis in a number of tumors. High levels of both the 24-kd [alpha]- and
      the 21-kd [beta]-isoform of caveolin-1 were detected in the nontumorigenic human
      fibroblast cell line IMR-90. In contrast, in HT-1080 human fibrosarcoma cells,
      caveolin-1 is strongly down-regulated. We show that the [alpha]-isoform of
      caveolin-1 is potently up-regulated in HT-1080 cells by inhibition of the mitogen
      activated protein kinase-signaling pathway with the specific inhibitor PD 98059,
      whereas the specific inhibitor of DNA methylation 5-aza-2'-deoxycytidine only
      marginally up-regulates caveolin-1. In addition, re-expression of caveolin-1 in
      HT-1080 fibrosarcoma cells potently inhibited colony formation. From these we
      conclude that caveolin-1 is likely to act as a tumor suppressor gene in human
      sarcomas.

PMID- 11238033
TI  - Endothelin receptor blockade inhibits proliferation of Kaposi's sarcoma cells.
AB  - Endothelin-1 (ET-1) has been shown to be mitogenic for endothelial and several
      tumor cells through an autocrine mechanism. In this study we evaluated whether
      the tumorigenic KS IMM cell line deriving from Kaposi's sarcoma (KS), a highly
      angiogenic tumor, is susceptible to ET-1 mitogenic activity. By reverse
      transcriptase-polymerase chain reaction, we detected ET-1 mRNA expression and
      both ET(A) receptor (ET(A)R) and ET(B)R mRNA transcripts in the KS IMM cells.
      High concentrations of ET-1 are released from the KS IMM cells and competition
      binding studies demonstrated that these cells also express functional ET(A)R and
      ET(B)R with high affinity for ET-1 and ET-1/ET-3, respectively. Expression of ET
      1 and cognate receptors could be detected by immunohistochemical method in vitro,
      in KS IMM xenograft, and in tissue sections of a human KS lesion. Furthermore ET
      1 induces a marked and dose-dependent increase in [3H]thymidine incorporation
      comparable to that elicited by vascular endothelial growth factor. Addition of
      both selective ET(B)R antagonist (BQ 788) and ET(A)R antagonist (BQ 123),
      completely blocked ET-1-induced mitogenic response and reduced the basal growth
      rate of unstimulated cells, suggesting that both receptors mediated the
      proliferative signal. Such findings demonstrate that ET-1 participates on KS
      pathogenesis acting as an autocrine growth factor and that ET-1 receptor
      antagonists may thus be novel candidates for therapeutic intervention.

PMID- 11238034
TI  - Expression of cyclooxygenase-2 in human transitional cell carcinoma of the
      urinary bladder.
AB  - Recent studies suggest that expression of cyclooxygenase-2 (Cox-2) is elevated in
      transitional cell carcinoma (TCC) of the urinary bladder and that inhibition of
      Cox-2 activity suppresses bladder cancer in experimental animal models. We have
      investigated the expression of Cox-2 protein in human TCCs (n = 85), in in situ
      carcinomas (Tis) of the urinary bladder (n = 17), and in nonneoplastic urinary
      bladder samples (n = 16) using immunohistochemistry. Cox-2 immunoreactivity was
      detected in 66% (67 of 102) of the carcinomas, whereas only 25% (4 of 16) of the
      nonneoplastic samples were positive (P: < 0.005). Cox-2 immunoreactivity
      localized to neoplastic cells in the carcinoma samples. The rate of positivity
      was the same in invasive (T1-3; 70%, n = 40) and in noninvasive (Tis and Ta; 65%,
      n = 62) carcinomas, but noninvasive tumors had a higher frequency (32%) of
      homogenous pattern of staining (>90% of the tumor cells positive) than the
      invasive carcinomas (10%) (P: < 0.05). However, several invasive TCCs exhibited
      the strongest intensity of Cox-2 staining in the invading cells, whereas other
      parts of the tumor were virtually negative. Finally, strong Cox-2 positivity was
      also found in nonneoplastic ulcerations (2 of 2) and in inflammatory pseudotumors
      (2 of 2), in which the immunoreactivity localized to the nonepithelial cells.
      Taken together, our data suggest that Cox-2 is highly expressed in noninvasive
      bladder carcinomas, whereas the highest expression of invasive tumors associated
      with the invading cells, and that Cox-2 may also have a pathophysiological role
      in nonneoplastic conditions of the urinary bladder, such as ulcerations and
      inflammatory pseudotumors.

PMID- 11238035
TI  - The transmembrane form of the CX3CL1 chemokine fractalkine is expressed
      predominantly by epithelial cells in vivo.
AB  - Fractalkine (CX3CL1) is synthesized as a type I transmembrane protein. Its unique
      CX(3)C chemokine domain is attached to a 241-amino acid mucin stalk, a 19-amino
      acid transmembrane domain, and a 37-amino acid intracellular domain of unknown
      function. A soluble form of fractalkine can be generated by proteolytic cleavage
      at the base of the mucin stalk. Novel monoclonal and polyclonal antibodies that
      specifically recognize only the amino- or carboxyl-terminal ends of the human
      fractalkine molecule have revealed that epithelial cells are the predominant cell
      type expressing transmembrane forms of fractalkine in human skin, the tonsil, and
      the large intestine. Using these specific anti-fractalkine reagents we do not
      detect high-level expression of fractalkine on endothelial cells in normal or
      inflamed colon samples obtained from patients with Crohn's disease or ulcerative
      colitis. In contrast to previous reports we do not detect fractalkine expression
      by Langerhans cells or immature dendritic cells in mucosal-associated lymphoid
      tissues in vivo. We show that the reagent used in previous studies, an anti
      fractalkine N-terminal peptide antisera, cross-reacts with human CD84. Finally we
      discuss potential roles for fractalkine in constitutive leukocyte trafficking
      based on its observed pattern of expression in epithelia.

PMID- 11238036
TI  - The beta-chemokine receptor D6 is expressed by lymphatic endothelium and a subset
      of vascular tumors.
AB  - The lymphatic vessels (lymphatics) play an important role in channeling fluid and
      leukocytes from the tissues to the secondary lymphoid organs. In addition to
      driving leukocyte egress from blood, chemokines have been suggested to contribute
      to leukocyte recirculation via the lymphatics. Previously, we have demonstrated
      that binding sites for several pro-inflammatory beta-chemokines are found on the
      endothelial cells (ECs) of lymphatics in human dermis. Here, using the MIP-1alpha
      isoform MIP-1alphaP, we have extended these studies to further support the
      contention that the in situ chemokine binding to afferent lymphatics exhibits
      specificity akin to that observed in vitro with the promiscuous beta-chemokine
      receptor D6. We have generated monoclonal antibodies to human D6 and showed D6
      immunoreactivity on the ECs lining afferent lymphatics, confirmed as such by
      staining serial skin sections with antibodies against podoplanin, a known
      lymphatic EC marker. In parallel, in situ hybridization on skin with antisense D6
      probes demonstrated the expression of D6 mRNA by lymphatic ECs. D6-immunoreactive
      lymphatics were also abundant in mucosa and submucosa of small and large
      intestine and appendix, but not observed in several other organs tested. In lymph
      nodes, D6 immunoreactivity was present on the afferent lymphatics and also in
      subcapsular and medullary sinuses. Tonsilar lymphatic sinuses were also D6
      positive. Peripheral blood cells and the ECs of blood vessels and high
      endothelial venules were consistently nonreactive with anti-D6 antibodies.
      Additionally, we have demonstrated that D6 immunoreactivity is detectable in some
      malignant vascular tumors suggesting they may be derived from, or phenotypically
      similar to, lymphatic ECs. This is the first demonstration of chemokine receptor
      expression by lymphatic ECs, and suggests that D6 may influence the chemokine
      driven recirculation of leukocytes through the lymphatics and modify the putative
      chemokine effects on the development and growth of vascular tumors.

PMID- 11238037
TI  - Macrophage myeloperoxidase regulation by granulocyte macrophage colony
      stimulating factor in human atherosclerosis and implications in acute coronary
      syndromes.
AB  - Inflammation and oxidative stress contribute to the pathogenesis of many human
      diseases including atherosclerosis. Advanced human atheroma contains high levels
      of the enzyme myeloperoxidase that produces the pro-oxidant species, hypochlorous
      acid (HOCl). This study documents increased numbers of myeloperoxidase-expressing
      macrophages in eroded or ruptured plaques causing acute coronary syndromes. In
      contrast, macrophages in human fatty streaks contain little or no
      myeloperoxidase. Granulocyte macrophage colony-stimulating factor, but not
      macrophage colony-stimulating factor, selectively regulates the ability of
      macrophages to express myeloperoxidase and produce HOCl in vitro. Moreover,
      myeloperoxidase-positive macrophages in plaques co-localized with granulocyte
      macrophage colony-stimulating factor. Pro-inflammatory stimuli known to be
      present in human atherosclerotic plaque, including CD40 ligand,
      lysophosphatidylcholine, or cholesterol crystals, could induce release of
      myeloperoxidase from HOCl production by macrophages in vitro. HOCl-modified
      proteins accumulated at ruptured or eroded sites of human coronary atheroma.
      These results identify granulocyte macrophage colony-stimulating factor as an
      endogenous regulator of macrophage myeloperoxidase expression in human
      atherosclerosis and support a particular role for the myeloperoxidase-expressing
      macrophages in atheroma complication and the acute coronary syndromes.

PMID- 11238038
TI  - Oxidative stress and induction of heme oxygenase-1 in the kidney in sickle cell
      disease.
AB  - Chronic nephropathy is a recognized complication of sickle cell disease. Using a
      transgenic sickle mouse, we examined whether oxidative stress occurs in the
      sickle kidney, the origins and functional significance of such oxidant stress,
      and the expression of the oxidant-inducible, potentially protective gene, heme
      oxygenase-1 (HO-1); we also examined the expression of HO-1 in the kidney and in
      circulating endothelial cells in sickle patients. We demonstrate that this
      transgenic sickle mouse exhibits renal enlargement, medullary congestion, and a
      reduced plasma creatinine concentration. Oxidative stress is present in the
      kidney as indicated by increased amounts of lipid peroxidation; heme content is
      markedly increased in the kidney. Exacerbation of oxidative stress by inhibiting
      glutathione synthesis with buthionine-sulfoximine dramatically increased red
      blood cell sickling in the sickle kidney: in buthionine-sulfoximine-treated
      sickle mice, red blood cell sickling extended from the medulla into the cortical
      capillaries and glomeruli. HO activity is increased in the sickle mouse kidney,
      and is due to induction of HO-1. In the human sickle kidney, HO-1 is induced in
      renal tubules, interstitial cells, and in the vasculature. Expression of HO-1 is
      increased in circulating endothelial cells in patients with sickle cell disease.
      These results provide the novel demonstration that oxidative stress occurs in the
      sickle kidney, and that acute exacerbation of oxidative stress in the sickle
      mouse precipitates acute vaso-occlusive disease. Additionally, the oxidant
      inducible, heme-degrading enzyme, HO-1, is induced regionally in the murine and
      human sickle kidney, and systemically, in circulating endothelial cells in sickle
      patients.

PMID- 11238039
TI  - Expression of hypoxia-inducible cell-surface transmembrane carbonic anhydrases in
      human cancer.
AB  - An acidic extracellular pH is a fundamental property of the malignant phenotype.
      In von Hippel-Lindau (VHL)-defective tumors the cell surface transmembrane
      carbonic anhydrase (CA) CA9 and CA12 genes are overexpressed because of the
      absence of pVHL. We hypothesized that these enzymes might be involved in
      maintaining the extracellular acidic pH in tumors, thereby providing a conducive
      environment for tumor growth and spread. Using Northern blot analysis and
      immunostaining with specific antibodies we analyzed the expression of CA9 and
      CA12 genes and their products in a large sample of cancer cell lines, fresh and
      archival tumor specimens, and normal human tissues. Expression was also analyzed
      in cultured cells under hypoxic conditions. Expression of CA IX and CA XII in
      normal adult tissues was detected only in highly specialized cells and for most
      tissues their expression did not overlap. Analysis of RNA samples isolated from
      87 cancer cell lines and 18 tumors revealed high-to-moderate levels of expression
      of CA9 and CA12 in multiple cancers. Immunohistochemistry revealed high-to
      moderate expression of these enzymes in various normal tissues and multiple
      common epithelial tumor types. The immunostaining was seen predominantly on the
      cell surface membrane. The expression of both genes was markedly induced under
      hypoxic conditions in tumors and cultured tumor cells. We conclude that the cell
      surface trans-membrane carbonic anhydrases CA IX and CA XII are overexpressed in
      many tumors suggesting that this is a common feature of cancer cells that may be
      required for tumor progression. These enzymes may contribute to the tumor
      microenvironment by maintaining extracellular acidic pH and helping cancer cells
      grow and metastasize. Our studies show an important causal link between hypoxia,
      extracellular acidification, and induction or enhanced expression of these
      enzymes in human tumors.

PMID- 11238040
TI  - Plasminogen activators direct reorganization of the liver lobule after acute
      injury.
AB  - Tissue repair requires an adequate cellular proliferation coordinated with the
      timely proteolysis of matrix elements. Based on the properties of plasminogen
      activators in liver cell proliferation and tissue proteolysis, we explored the
      regulatory role of tissue-type plasminogen activator (tPA) and urokinase-type
      plasminogen activator (uPA) in liver repair. Using carbon tetrachloride (CCl(4))
      intoxication as a model of acute liver injury, we found that tPA-deficient mice
      displayed a mild defect in hepatic repair, whereas livers of uPA-deficient mice
      had a more substantial delay in repair, with injury of centrilobular hepatocytes
      persisting up to 14 days after CCl(4). Notably, functional cooperativity between
      plasminogen activators was strongly inferred from the profound reparative defect
      in livers of mice lacking tPA and uPA simultaneously, with persistence of
      centrilobular injury as far out as 35 days. The defective repair was not because
      of increased susceptibility of experimental mice to the toxin or to inadequate
      cellular proliferation. Instead, lack of plasminogen activators led to the
      accumulation of fibrin and fibronectin within injured areas and poor removal of
      necrotic cells. These data demonstrate that tPA and uPA play a critical role in
      hepatic repair via proteolysis of matrix elements and clearance of cellular
      debris from the field of injury.

PMID- 11238042
TI  - Basic fibroblast growth factor and ultraviolet B transform melanocytes in human
      skin.
AB  - Ultraviolet (UV) light is an epidemiological risk factor for melanoma, but its
      specific contribution to melanoma induction is not known. The first critical step
      of melanoma development, ie, the uncontrolled proliferation of melanocytes, may
      be induced by a combination of UV damage and an imbalance of growth factor
      production by cells in the immediate area of the melanocyte. Among several
      candidates, basic fibroblast growth factor (bFGF) is the major autocrine growth
      factor in melanoma and associated with tumor progression. Overexpression of bFGF
      via adenoviral gene transfer in human skin xenografted to severe combined
      immunodeficiency mice led to black-pigmented macules within 3 weeks of treatment.
      Immunofluorescence analysis demonstrated pathological hyperpigmentation,
      proliferation and hyperplasia of activated melanocytes, but no malignant
      transformation. Similar changes were observed in skin reconstructs. When bFGF was
      combined with UVB, pigmented lesions with hyperplastic melanocytic cells were
      detected, including a lesion with high-grade atypia resembling lentiginous forms
      of malignant melanoma. Donor-matched control grafts revealed no melanocytic
      changes. bFGF was overexpressed in dermal fibroblasts demonstrating the co
      carcinogenic influence of paracrine-acting growth factors by cells of the
      microenvironment. This is the first report suggesting that an imbalance of
      physiological growth factor production in the skin may cause melanoma in
      combination with UVB.

PMID- 11238041
TI  - Inhibition of type I procollagen synthesis by damaged collagen in photoaged skin
      and by collagenase-degraded collagen in vitro.
AB  - Type I and type III procollagen are reduced in photodamaged human skin. This
      reduction could result from increased degradation by metalloproteinases and/or
      from reduced procollagen synthesis. In the present study, we investigated type I
      procollagen production in photodamaged and sun-protected human skin. Skin samples
      from severely sun-damaged forearm skin and matched sun-protected hip skin from
      the same individuals were assessed for type I procollagen gene expression by in
      situ hybridization and for type I procollagen protein by immunostaining. Both
      mRNA and protein were reduced ( approximately 65 and 57%, respectively) in
      photodamaged forearm skin compared to sun-protected hip skin. We next
      investigated whether reduced type I procollagen production was because of
      inherently reduced capacity of skin fibroblasts in severely photodamaged forearm
      skin to synthesize procollagen, or whether contextual influences within
      photodamaged skin act to down-regulate type I procollagen synthesis. For these
      studies, fibroblasts from photodamaged skin and matched sun-protected skin were
      established in culture. Equivalent numbers of fibroblasts were isolated from the
      two skin sites. Fibroblasts from the two sites had similar growth capacities and
      produced virtually identical amounts of type I procollagen protein. These
      findings indicate that the lack of type I procollagen synthesis in sun-damaged
      skin is not because of irreversible damage to fibroblast collagen-synthetic
      capacity. It follows, therefore, that factors within the severely photodamaged
      skin may act in some manner to inhibit procollagen production by cells that are
      inherently capable of doing so. Interactions between fibroblasts and the
      collagenous extracellular matrix regulate type I procollagen synthesis. In sun
      protected skin, collagen fibrils exist as a highly organized matrix. Fibroblasts
      are found within the matrix, in close apposition with collagen fibers. In
      photodamaged skin, collagen fibrils are shortened, thinned, and disorganized. The
      level of partially degraded collagen is approximately 3.6-fold greater in
      photodamaged skin than in sun-protected skin, and some fibroblasts are surrounded
      by debris. To model this situation, skin fibroblasts were cultured in vitro on
      intact collagen or on collagen that had been partially degraded by exposure to
      collagenolytic enzymes. Collagen that had been partially degraded by exposure to
      collagenolytic enzymes from either bacteria or human skin underwent contraction
      in the presence of dermal fibroblasts, whereas intact collagen did not.
      Fibroblasts cultured on collagen that had been exposed to either source of
      collagenolytic enzyme demonstrated reduced proliferative capacity (22 and 17%
      reduction on collagen degraded by bacterial collagenase or human skin
      collagenase, respectively) and synthesized less type I procollagen (36 and 88%
      reduction, respectively, on a per cell basis). Taken together, these findings
      indicate that 1) fibroblasts from photoaged and sun-protected skin are similar in
      their capacities for growth and type I procollagen production; and 2) the
      accumulation of partially degraded collagen observed in photodamaged skin may
      inhibit, by an as yet unidentified mechanism, type I procollagen synthesis.

PMID- 11238043
TI  - HOX genes in human lung: altered expression in primary pulmonary hypertension and
      emphysema.
AB  - HOX genes belong to the large family of homeodomain genes that function as
      transcription factors. Animal studies indicate that they play an essential role
      in lung development. We investigated the expression pattern of HOX genes in human
      lung tissue by using microarray and degenerate reverse transcriptase-polymerase
      chain reaction survey techniques. HOX genes predominantly from the 3' end of
      clusters A and B were expressed in normal human adult lung and among them HOXA5
      was the most abundant, followed by HOXB2 and HOXB6. In fetal (12 weeks old) and
      diseased lung specimens (emphysema, primary pulmonary hypertension) additional
      HOX genes from clusters C and D were expressed. Using in situ hybridization,
      transcripts for HOXA5 were predominantly found in alveolar septal and epithelial
      cells, both in normal and diseased lungs. A 2.5-fold increase in HOXA5 mRNA
      expression was demonstrated by quantitative reverse transcriptase-polymerase
      chain reaction in primary pulmonary hypertension lung specimens when compared to
      normal lung tissue. In conclusion, we demonstrate that HOX genes are selectively
      expressed in the human lung. Differences in the pattern of HOX gene expression
      exist among fetal, adult, and diseased lung specimens. The altered pattern of HOX
      gene expression may contribute to the development of pulmonary diseases.

PMID- 11238044
TI  - NF-kappaB is activated in cholestasis and functions to reduce liver injury.
AB  - Selected bile acids activate a nuclear factor-kappa B (NF-kappaB)-dependent
      survival signaling cascade in cultured hepatocytes. These data suggest that in
      cholestasis where liver tissue bile acid concentrations are increased, NF-kappaB
      should be activated and inhibition of NF-kappaB should potentiate liver injury.
      Our aims were to test these two predictions. Cholestasis was obtained by common
      bile duct ligation in mice. NF-kappaB activation was demonstrated in nuclear
      extracts by the electrophoretic mobility gel shift assay from 3-day bile duct
      ligated (BDL) mice but not in controls. Immunohistochemistry for NF-kappaB
      demonstrated nuclear localization in hepatocytes of BDL mice consistent with its
      activation in this liver cell type. Electrophoretic mobility gel shift assay and
      immunohistochemistry for NF-kappaB in BDL tumor necrosis factor-receptor 1
      knockout mice demonstrated hepatocyte NF-kappaB activation, suggesting that tumor
      necrosis factor-alpha was not responsible for the activation of this
      transcription factor. Liver injury was assessed in BDL mice after administration
      of the adenovirus 5 inhibitor of kappa B superrepressor (Ad5IkappaBsr) to inhibit
      NF-kappaB. TUNEL-positive cells and serum alanine aminotransferase values were
      increased at least threefold in mice treated with the Ad5IkappaBsr versus the
      empty virus. Liver histology also demonstrated increased liver injury in the BDL
      mice treated with the Ad5IkappaBsr. In conclusion, NF-kappaB is activated in
      hepatocytes during obstructive cholestasis and functions to reduce liver injury.

PMID- 11238045
TI  - CD28-B7-mediated T cell costimulation in chronic cardiac allograft rejection:
      differential role of B7-1 in initiation versus progression of graft
      arteriosclerosis.
AB  - Provision of adequate T cell costimulation is critical for the development of
      acute and chronic allograft rejection. We have previously reported that early
      blockade of CD28-B7 T cell costimulation prevents the development of graft
      arteriosclerosis, in the LEW into F344 rat cardiac transplant model. In this
      study, we used the same model to examine the requirement for CD28-B7-mediated T
      cell costimulation in the progression of established chronic rejection and
      examined the individual roles of B7-1 (CD80) and B7-2 (CD86) costimulatory
      molecules. Late blockade of CD28-B7 T cell costimulation by the fusion protein
      CTLA4Ig, which binds both CD80 and CD86, attenuated the development of transplant
      arteriosclerosis, mononuclear cell infiltration, and parenchymal fibrosis in this
      model. Selective blockade of CD80 using the mutant fusion protein Y100F was as
      effective as CTLA4Ig in this regard. In contrast to CTLA4Ig, blockade of CD80
      alone by Y100F was ineffective at preventing early graft loss and prolonging
      graft survival when given early after transplantation. This study is the first to
      demonstrate that late blockade of CD28-B7 T cell costimulation interrupts chronic
      cardiac allograft rejection, and it indicates the importance of continued T cell
      activation in this process. This study further defines functional differences
      between CD80 and CD86 costimulatory molecules in vivo.

PMID- 11238046
TI  - Beta-catenin dysregulation in thyroid neoplasms: down-regulation, aberrant
      nuclear expression, and CTNNB1 exon 3 mutations are markers for aggressive tumor
      phenotypes and poor prognosis.
AB  - beta-catenin has a role in cell adhesion and Wnt signaling. It is mutated or
      otherwise dysregulated in a variety of human cancers. In this study we assess
      beta-catenin alteration in 145 thyroid tumors samples from 127 patients. beta
      catenin was localized using immunofluorescence and mutational analysis was
      performed by single-strand conformational polymorphism. Membrane beta-catenin
      expression was decreased in eight of 12 (66%) adenomas and in all 115 carcinomas
      (P: < 0.0001). Among carcinomas, reduced membrane beta-catenin was associated
      with progressive loss of tumor differentiation (P: < 0.0001). CTNNB1 exon 3
      mutations and nuclear beta-catenin localization were restricted to poorly
      differentiated [7 of 28 (25%) and 6 of 28 cases (21.4%), respectively] or
      undifferentiated carcinomas [19 of 29 (65.5%) and 14 of 29 (48.3%) cases,
      respectively]. Poorly differentiated tumors always featured mutations involving
      Ser and Thr residues and were characterized by Thr to Ile amino acid
      substitutions (P: = 0.0283). The association between CTNNB1 exon 3 mutations and
      aberrant nuclear immunoreactivity (P: = 0.0020) is consistent with Wnt activation
      because of stabilizing beta-catenin mutations. Low membrane beta-catenin
      expression as well as its nuclear localization or CTNNB1 exon 3 mutations are
      significantly associated with poor prognosis, independent of conventional
      prognostic indicators for thyroid cancer but not of tumor differentiation.
      Analysis of beta-catenin dysregulation may be useful to objectively subtype
      thyroid neoplasms and more accurately predict outcomes.

PMID- 11238047
TI  - PG490-88, a derivative of triptolide, blocks bleomycin-induced lung fibrosis.
AB  - In this study we evaluate the antifibrotic properties of PG-490-88, a water
      soluble derivative of triptolide. Triptolide is an oxygenated diterpene that is
      derived from a traditional Chinese herb that has potent immunosuppressive and
      antitumor activity. We used the intratracheal bleomycin mouse model and found
      that PG490-88 inhibits fibrosis in the bleomycin group when given the same day or
      5 days after bleomycin. PG490-88 also markedly reduced the number of
      myofibroblasts in the bleomycin treatment group. An enzyme-linked immunosorbent
      assay of transforming growth factor (TGF)-beta in the bronchoalveolar lavage
      fluid showed a significant decrease in TGF-beta in the PG490-88-treated groups
      compared to the bleomycin-treated group. Additionally, triptolide blocked
      bleomycin-induced increase in TGF-beta mRNA in cultured normal human lung
      fibroblasts. The efficacy of PG490-88 when administered late after bleomycin
      installation suggests a potential role in the treatment of idiopathic pulmonary
      fibrosis.

PMID- 11238048
TI  - Sporadic fundic gland polyps: common gastric polyps arising through activating
      mutations in the beta-catenin gene.
AB  - Fundic gland polyps (FGPs) are the most common gastric polyps. FGPs traditionally
      have been regarded as nondysplastic hamartomatous or hyperplastic lesions, but
      their pathogenesis remains unclear. We have recently shown that somatic
      adenomatous polyposis coli (APC) gene alterations are frequently present in FGPs
      associated with familial adenomatous polyposis (FAP), raising the possibility
      that mutations of the beta-catenin gene affecting the APC/beta-catenin pathway
      might be involved in the pathogenesis of sporadic FGPs. We analyzed somatic beta
      catenin gene mutations in 57 sporadic FGPs from 40 patients without FAP and in 19
      FGPs from 13 FAP patients. Direct DNA sequencing of exon 3 encompassing the
      glycogen synthase kinase-3beta phosphorylation region for beta-catenin was used
      with confirmation by HIN:fI restriction endonuclease digestion. The foveolar
      epithelium and dilated fundic glands of the polyps were separately microdissected
      and analyzed in 22 of 57 sporadic FGPs. Activating beta-catenin gene mutations
      were present in 91% (52 of 57) of sporadic FGPs. Both the foveolar epithelium and
      the dilated fundic gland epithelium comprising the polyps were shown to have the
      same somatic beta-catenin mutation in 21 of 22 (95%) sporadic FGPs. In contrast,
      beta-catenin gene mutations were not present in any of the 19 FAP-associated FGPs
      (P: < 0.000001). The high frequency of beta-catenin mutations in sporadic FGPs
      indicates that these lesions arise through activating mutations of the beta
      catenin gene. Beta-catenin mutations in gastrointestinal tract polyps have
      previously only been demonstrated in a subset of adenomatous (dysplastic) or
      neoplastic polyps. Sporadic FGPs are therefore the only lesions of the
      gastrointestinal tract to demonstrate beta-catenin mutations while lacking
      dysplastic morphology.

PMID- 11238049
TI  - Expression of the hypoxia-inducible and tumor-associated carbonic anhydrases in
      ductal carcinoma in situ of the breast.
AB  - Carbonic anhydrases (CA) influence intra- and extracellular pH and ion transport
      in varied biological processes. We recently identified CA9 and CA12 as hypoxia
      inducible genes. In this study we examined the expression of these tumor
      associated CAs by immunohistochemistry in relation to necrosis and early breast
      tumor progression in 68 cases of ductal carcinoma in situ (DCIS) (39 pure DCIS
      and 29 DCIS associated with invasive carcinoma). CA IX expression was rare in
      normal epithelium and benign lesions, but was present focally in DCIS (50% of
      cases) and in associated invasive carcinomas (29%). In comparison, CA XII was
      frequently expressed in normal breast tissues (89%), in DCIS (84%), and in
      invasive breast lesions (71%). In DCIS, CA IX was associated with necrosis (P: =
      0.0053) and high grade (P: = 0.012). In contrast, CA XII was associated with the
      absence of necrosis (P: = 0.036) and low grade (P: = 0.012). Despite this,
      augmented CA XII expression was occasionally observed adjacent to necrosis within
      high-grade lesions. Neither CA IX nor CA XII expression was associated with
      regional or overall proliferation as determined by MIB1 staining. Assessment of
      mammographic calcification showed that CA XII expression was associated with the
      absence of calcification (n = 43, P: = 0.0083). Our results demonstrate that
      induction of CA IX and CA XII occurs in regions adjacent to necrosis in DCIS.
      Furthermore, these data suggest that proliferation status does not influence
      expression of either CA in breast tissues, that hypoxia may be a dominant factor
      in the regulation of CA IX, and that factors related to differentiation, as
      determined by tumor grade, dominate the regulation of CA XII. The existence of
      differential regulation and associations with an aggressive phenotype may be
      important in the development of selective inhibitors of CAs, because the latter
      have recently been shown to prevent tumor invasion.

PMID- 11238050
TI  - Protection of ATP-depleted cells by impermeant strychnine derivatives:
      implications for glycine cytoprotection.
AB  - Glycine and structurally related amino acids with activities at chloride channel
      receptors in the central nervous system also have robust protective effects
      against cell injury by ATP depletion. The glycine receptor antagonist strychnine
      shares this protective activity. An essential step toward identification of the
      molecular targets for these compounds is to determine whether they protect cells
      through interactions with intracellular targets or with molecules on the outer
      surface of plasma membranes. Here we report cytoprotection by a cell-impermeant
      derivative of strychnine. A strychnine-fluorescein conjugate (SF) was
      synthesized, and impermeability of plasma membranes to this compound was verified
      by fluorescence confocal microscopy. In an injury model of Madin-Darby canine
      kidney cells, ATP depletion led to lactate dehydrogenase release. SF prevented
      lactate dehydrogenase leakage without ameliorating ATP depletion. This was
      accompanied by preservation of cellular ultrastructure and exclusion of vital
      dyes. SF protection was also shown for ATP-depleted rat hepatocytes. On the other
      hand, when a key structural motif in the active site of strychnine was chemically
      blocked, the SF lost its protective effect, establishing strychnine-related
      specificity for SF protection. Cytoprotective effects of the cell-impermeant
      strychnine derivative provide compelling evidence suggesting that molecular
      targets on the outer surface of plasma membranes may mediate cytoprotection by
      strychnine and glycine.

PMID- 11238051
TI  - A putative role for cathepsin K in degradation of AA and AL amyloidosis.
AB  - The aims of this study were to investigate the role of cathepsin K in the
      pathology of amyloidosis by demonstrating its presence in multinucleated giant
      cells (MGCs) adjacent to amyloid deposits, and determining its ability to degrade
      amyloid fibril proteins in vitro. The study was performed using autopsy and
      biopsy specimens from patients with AA or AL amyloidosis. In six (55%) patients
      with AA amyloidosis and seven (58%) patients with AL amyloidosis, variable
      numbers of CD68-immunoreactive MGCs were found adjacent to amyloid deposits. In
      each case strong cytoplasmic immunostaining for cathepsin K was found in MGCs;
      immunostaining of amyloid deposits was present in five (45%) patients with AA
      amyloidosis and three (25%) patients with AL amyloidosis. In vitro degradation
      experiments showed that recombinant cathepsin K completely degraded AA amyloid
      fibril proteins at pH 5.5 as shown by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and Western blotting. Less effective degradation took place at pH
      7.4 and there was no degradation in the presence of a general cysteine protease
      inhibitor (E64) or in the absence of cathepsin K. This is the first study to show
      that cathepsin K is expressed in MGCs adjacent to amyloid deposits and to
      demonstrate its ability to degrade amyloid fibril proteins.

PMID- 11238052
TI  - Generation of C-reactive protein and complement components in atherosclerotic
      plaques.
AB  - C-reactive protein (CRP) and complement are hypothesized to be major mediators of
      inflammation in atherosclerotic plaques. We used the reverse transcriptase
      polymerase chain reaction technique to detect the mRNAs for CRP and the classical
      complement components C1 to C9 in both normal arterial and plaque tissue,
      establishing that they can be endogenously generated by arteries. When the CRP
      mRNA levels of plaque tissue, normal artery, and liver were compared in the same
      cases, plaque levels were 10.2-fold higher than normal artery and 7.2-fold higher
      than liver. By Western blotting, we showed that the protein levels of CRP and
      complement proteins were also up-regulated in plaque tissue and that there was
      full activation of the classical complement pathway. By in situ hybridization, we
      detected intense signals for CRP and C4 mRNAs in smooth muscle-like cells and
      macrophages in the thickened intima of plaques. By immunohistochemistry we showed
      co-localization of CRP and the membrane attack complex of complement. We also
      detected up-regulation in plaque tissue of the mRNAs for the macrophage markers
      CD11b and HLA-DR, as well as their protein products. We showed by
      immunohistochemistry macrophage infiltration of plaque tissue. Because CRP is a
      complement activator, and activated complement attacks cells in plaque tissue,
      these data provide evidence of a self-sustaining autotoxic mechanism operating
      within the plaques as a precursor to thrombotic events.

PMID- 11238054
TI  - Structural and functional disruption of vascular smooth muscle cells in a
      transgenic mouse model of amyloid angiopathy.
AB  - The deposition of amyloid Abeta peptide in the wall of cerebral vessels (cerebral
      amyloid angiopathy), can lead to weakness and rupture of the vessel wall,
      resulting in hemorrhagic stroke. The Tg2576 transgenic mouse line, overexpressing
      mutant amyloid precursor protein in an age-dependent manner, forms amyloid
      angiopathy morphologically similar to that seen in the human. We report here the
      structural and functional disruption of smooth muscle cells (SMCs) in the walls
      of pial vessels affected by amyloid deposition in the Tg2576 mouse. We
      demonstrate, using multiphoton imaging, that the arrangement of SMCs becomes
      disorganized before the onset of cell death, and that these disorganized SMCs are
      unable to respond appropriately to application of endothelial-dependent and
      endothelial-independent vasodilators in a closed-cranial window preparation.

PMID- 11238053
TI  - Chemokine-induced cutaneous inflammatory cell infiltration in a model of Hu-PBMC
      SCID mice grafted with human skin.
AB  - Recently, certain chemokines and chemokine receptors have been preferentially
      associated with the selective recruitment in vitro of type 1 T cells, such as IP
      10 and its receptor CXCR3, or type 2 T cells such as monocyte-derived chemokine
      (MDC) and eotaxin and their receptors CCR4 and CCR3. Very few models have
      provided confirmation of these findings in vivo. Taking advantage of the
      humanized SCID mouse model grafted with autologous human skin, the ability of the
      chemokines IP-10, MDC, eotaxin, and RANTES to stimulate cell recruitment was
      investigated. Intradermal IP-10 injection resulted in an influx of CD4+ T
      lymphocytes but also surprisingly in the recruitment of dendritic cells. MDC
      recruited mainly CD8+ T lymphocytes, and had little effect on eosinophils. As
      predicted, eotaxin was a potent inducer of eosinophil and basophil migration,
      also recruiting CD4+ T cells. RANTES, a ubiquitous chemokine associated with both
      type 1 and type 2 profiles, was able to recruit all cell types. CXCR3-positive
      cells were preferentially recruited by IP-10, whereas CCR3- and CCR4-positive
      cells were predominantly found after injection of eotaxin and MDC. Thus, in a
      human environment in vivo, some chemokines have the ability to recruit cells
      expressing chemokine receptors preferentially expressed on type 1 or type 2
      cells. Further investigations revealed that MDC and eotaxin induced the
      recruitment of type 2, but not type 1, cytokine-producing cells. RANTES, on the
      other hand, induced the migration of both type 1 and type 2 cytokine-secreting
      cells, whereas IP-10 did not induce the recruitment of either subtype. These
      studies provide detailed information on the properties of MDC, eotaxin, IP-10,
      and RANTES as chemotactic molecules in skin in vivo. The use of the humanized
      SCID mouse model grafted with human skin is validated as a useful model for the
      evaluation of chemokine function in the inflammatory reaction, and suggests that
      therapeutic targeting of certain chemokines might be of interest in diseases
      associated preferentially with a type 1 or type 2 profile.

PMID- 11238055
TI  - Frequent beta-catenin mutations in juvenile nasopharyngeal angiofibromas.
AB  - Juvenile nasopharyngeal angiofibromas (JNAs) are locally aggressive vascular
      tumors occurring predominantly in adolescent males. The pathogenesis of JNAs is
      unknown. Recently, JNAs have been reported to occur at increased frequency among
      patients with familial adenomatous polyposis, suggesting that alterations of the
      adenomatous polyposis coli (APC)/beta-catenin pathway might also be involved in
      the pathogenesis of sporadic JNAs. We analyzed somatic beta-catenin and APC gene
      mutations in 16 sporadic JNAs from nonfamilial adenomatous polyposis patients
      using immunohistochemistry for beta-catenin, and direct DNA sequencing for exon 3
      of the beta-catenin gene and the mutation cluster region of the APC gene. Nuclear
      accumulation of beta-catenin was diffusely present in the stromal cells but not
      in the endothelial cells of all 16 JNAs. Activating beta-catenin gene mutations
      were present in 75% (12 of 16) of JNAs. Six JNA patients also had recurrent
      tumors after surgery, and in all cases the beta-catenin gene status of the
      recurrent JNA was identical to the initial tumor. No mutations in the mutation
      cluster region of the APC gene were detected in the four JNAs without beta
      catenin mutations. The high frequency of beta-catenin mutations in sporadic JNAs
      and the presence of identical beta-catenin gene mutations in recurrent tumors
      indicates that activating beta-catenin gene mutations are important in the
      pathogenesis of JNAs. The immunohistochemical localization of beta-catenin only
      to the nuclei of stromal cells further suggests that the stromal cells, rather
      than endothelial cells, are the neoplastic cells of JNAs.

PMID- 11238056
TI  - Disruption of integrin function in the murine myocardium leads to perinatal
      lethality, fibrosis, and abnormal cardiac performance.
AB  - The molecular mechanisms that regulate the cardiac hypertrophic response and the
      progression from compensated hypertrophy to decompensated heart failure have not
      been thoroughly defined. Alteration in cardiac extracellular matrix is a
      distinguishing characteristic of these pathological processes. Integrins, cell
      surface receptors that mediate cellular adhesion to the extracellular matrix, are
      signaling molecules that possess mechanotransduction properties. Therefore, we
      hypothesized that integrins are likely candidates to play an important role in
      cardiac function. To test this hypothesis, transgenic mice were constructed in
      which normal integrin function was disrupted by expression of a chimeric molecule
      encoding the transmembrane and extracellular domains of the Tac subunit of the IL
      2 receptor, fused to the cytoplasmic domain of beta(1A) integrin (Tacbeta(1A)).
      Using the alpha myosin heavy chain promoter to target expression of this chimera
      to the cardiac myocyte, transgenic mice were generated that had varied levels of
      transgene expression. Multiple transgenic founders that expressed the transgene
      at high levels, died perinatally and exhibited replacement fibrosis. Lines that
      survived showed 1) hypertrophic changes concordant with reduction in endogenous
      beta(1) integrin levels, or 2) reduced basal contractility and relaxation as well
      as alterations in components of integrin signaling pathways. These data support
      an important role for beta(1) integrin in normal cardiac function.

PMID- 11238057
TI  - High glucose-induced hypertrophy of mesangial cells requires p27(Kip1), an
      inhibitor of cyclin-dependent kinases.
AB  - Hypertrophy of mesangial cells is one of the earliest morphological alterations
      in the kidney after the onset of diabetes mellitus. We have previously shown that
      cultured mesangial cells exposed to high ambient glucose arrest in the G1 phase
      of the cell cycle and that this is associated with an increased expression of
      inhibitors of the cyclin-dependent kinase (CDK)-inhibitors p21(Cip) and
      p27(Kip1). To further investigate a potential role of p27Kip1 in the development
      of glucose-induced hypertrophy, mesangial cells from p27Kip1 wild-type (+/+) and
      knockout (-/-) mice were established. High glucose medium (450 mg/dl) increased
      p21(Cip1) protein in p27Kip1+/+ and -/- mesangial cells, and increased p27Kip1
      protein levels in p27Kip1+/+ cells. In contrast to high glucose increasing de
      novo protein synthesis in p27Kip1+/+ cells, high glucose did not increase protein
      synthesis in p27Kip1-/- cells. High glucose also reduced DNA synthesis and caused
      cell cycle arrest in p27Kip1+/+ cells. In contrast, despite an increase in
      transforming growth factor (TGF)-beta mRNA and protein expression, DNA synthesis
      and cell cycle progression were increased by high glucose in p27Kip1-/- cells.
      Exogenous TGF-beta comparably induced fibronectin mRNA in p27Kip1+/+ and -/-
      cells suggesting intact TGF-beta receptor transduction. In addition, high glucose
      failed to increase the total protein/cell number ratio in p27Kip1-/- cells.
      However, in the presence of high glucose, reconstituting p27Kip1 expression by
      transient or stable transfection in p27Kip1-/- cells, using an inducible
      expression system, increased the de novo protein synthesis and restored G1-phase
      arrest. These results show that p27Kip1 is required for glucose-induced mesangial
      cell hypertrophy and cell cycle arrest.

PMID- 11238058
TI  - Monocyte/macrophage activation by normal bacteria and bacterial products:
      implications for altered epithelial function in Crohn's disease.
AB  - Intestinal immune cells are less reactive than those in the peripheral blood;
      however, such cells from patients with Crohn's disease may be more responsive to
      bacterial products. Our study examined if nonpathogenic bacteria or
      lipopolysaccharide (LPS), can affect epithelial function in the presence of
      monocytes/macrophages. Lamina propria mononuclear cells (LPMCs) and peripheral
      blood monocytes (PBMs) were obtained from patients with Crohn's disease and
      control patients. Filter-grown T84 epithelial monolayers were co-cultured with
      nonactivated or LPS-activated LPMCs or PBMs for 48 hours. Epithelial secretory
      [baseline short-circuit current (Isc) and DeltaIsc to forskolin] and barrier
      (transepithelial electrical resistance) parameters were measured in Ussing
      chambers. LPS-activated PBMs from both controls and patients with Crohn's disease
      significantly increased Isc ( approximately 300%) and reduced transepithelial
      electrical resistance ( approximately 40%). Epithelial function was not altered
      after co-culture with control LPMCs +/- LPS. However, LPMCs from patients with
      Crohn's disease spontaneously secreted tumor necrosis factor-alpha, and induced
      epithelial changes similar to those produced by LPS-activated PBMs. Co-culture
      with control Escherichia coli and PBMs induced comparable changes in epithelial
      physiology, which were abrogated by anti-tumor necrosis factor-alpha antibody. We
      conclude that LPMCs of patients with Crohn's disease are spontaneously activated,
      possibly by gram-negative luminal bacteria, and can directly cause significant
      alterations in epithelial ion transport and barrier functions.

PMID- 11238059
TI  - Hepatocyte growth factor enhances vascular endothelial growth factor-induced
      angiogenesis in vitro and in vivo.
AB  - Vascular endothelial growth factor (VEGF) is an important mediator of
      angiogenesis in both physiological and pathological processes. Hepatocyte growth
      factor (HGF) is a mesenchyme-derived mitogen that also stimulates cell migration,
      and branching and/or tubular morphogenesis of epithelial and endothelial cells.
      In the present study, we tested the hypothesis that simultaneous administration
      of HGF and VEGF would synergistically promote new blood vessel formation. HGF
      acted in concert with VEGF to promote human endothelial cell survival and
      tubulogenesis in 3-D type I collagen gels, a response that did not occur with
      either growth factor alone. The synergistic effects of VEGF and HGF on
      endothelial survival correlated with greatly augmented mRNA levels for the anti
      apoptotic genes Bcl-2 and A1. Co-culture experiments with human neonatal dermal
      fibroblasts and human umbilical vein endothelial cells demonstrated that neonatal
      dermal fibroblasts, in combination with VEGF, stimulated human umbilical vein
      endothelial cells tubulogenesis through the paracrine secretion of HGF. Finally,
      in vivo experiments demonstrated that the combination of HGF and VEGF increased
      neovascularization in the rat corneal assay greater than either growth factor
      alone. We suggest that combination therapy using HGF and VEGF co-administration
      may provide a more effective strategy to achieve therapeutic angiogenesis.

PMID- 11238060
TI  - Primary ovarian carcinomas display multiple methylator phenotypes involving known
      tumor suppressor genes.
AB  - Mounting evidence suggests that aberrant methylation of CpG islands is a major
      pathway leading to the inactivation of tumor suppressor genes and the development
      of cancer. Recent studies on colorectal and gastric cancer have defined a CpG
      island methylator phenotype (CIMP), which involves the targeting of multiple
      genes by promoter hypermethylation. To determine the role of methylation in
      ovarian cancer, we have investigated the methylation status of 93 primary ovarian
      tumors at ten loci using methylation-specific polymerase chain reaction (MSP).
      Seven of the loci (BRCA1, HIC1, MINT25, MINT31, MLH1, p73 and hTR) were found to
      be methylated in a significant proportion of the ovarian tumors, and methylation
      of at least one of these was found in the majority (71%) of samples. Although
      concurrent methylation of multiple genes was commonly seen, this did not seem to
      be due to a single CIMP phenotype. Instead the results suggest the presence of at
      least three groups of tumors, two CIMP-positive groups, each susceptible to
      methylation of a different subset of genes, and a further group of tumors not
      susceptible to CpG island methylation, at least at the loci studied.

PMID- 11238061
TI  - Investigation into the mechanism of the loss of laminin 5 (alpha3beta3gamma2)
      expression in prostate cancer.
AB  - Laminin 5 is a pivotal hemidesmosomal protein involved in cell stability,
      migration, and anchoring filament formation. Protein and gene expression of the
      alpha3, beta3, and gamma2 chains of laminin 5 were investigated in normal and
      invasive prostate carcinoma using immunohistochemistry, Northern analysis, and in
      situ hybridization. Laser capture microdissection of normal and carcinomatous
      glands, in conjunction with RNA amplification and reverse Northern analysis, were
      used to confirm the gene expression data. Protein and mRNA expression of all
      three laminin 5 chains were detected in the basal cells of normal glands. In
      contrast, invasive prostate carcinoma showed a loss of beta3 and gamma2 protein
      expression with variable expression of alpha3 chains. Despite the loss of protein
      expression, there was retention of beta3 and gamma2 mRNA expression as detected
      by in situ hybridization, Northern and reverse Northern analysis. Our findings
      imply that an altered mechanism of translation of beta3 or gamma2 mRNAs into
      functional proteins contributes to failure of anchoring filaments and
      hemidesmosomal formation. The resultant hemidesmosome instability or loss would
      suggest a less stable epithelial-stromal junction, increased invasion and
      migration of malignant cells, and disruption of normal integrin signaling
      pathways.

PMID- 11238062
TI  - Chromosomal abnormalities subdivide ependymal tumors into clinically relevant
      groups.
AB  - Ependymoma occurs most frequently within the central nervous system of children
      and young adults. We determined relative chromosomal copy-number aberrations in
      44 ependymomas using comparative genomic hybridization. The study included 24
      intracranial and 20 spinal cord tumors from pediatric and adult patients.
      Frequent chromosomal aberrations in intracranial tumors were gain of 1q and
      losses on 6q, 9, and 13. Gain of 1q and loss on 9 were preferentially associated
      with histological grade 3 tumors. On the other hand, gain on chromosome 7 was
      recognized almost exclusively in spinal cord tumors, and was associated with
      various other chromosomal aberrations including frequent loss of 22q. We conclude
      that cytogenetic analysis of ependymomas may help to classify these tumors and
      provide leads concerning their initiation and progression. The relationship of
      these aberrations to patient outcome needs to be addressed.

PMID- 11238064
TI  - Intrachoroidal neovascularization in transgenic mice overexpressing vascular
      endothelial growth factor in the retinal pigment epithelium.
AB  - Choroidal neovascularization in age-related macular degeneration is a frequent
      and poorly treatable cause of vision loss in elderly Caucasians. This choroidal
      neovascularization has been associated with the expression of vascular
      endothelial growth factor (VEGF). In current animal models choroidal
      neovascularization is induced by subretinal injection of growth factors or
      vectors encoding growth factors such as VEGF, or by disruption of the Bruch's
      membrane/retinal pigment epithelium complex with laser treatment. We wished to
      establish a transgenic murine model of age-related macular degeneration, in which
      the overexpression of VEGF by the retinal pigment epithelium induces choroidal
      neovascularization. A construct consisting of a tissue-specific murine retinal
      pigment epithelium promoter (RPE(65) promoter) coupled to murine VEGF(164) cDNA
      with a rabbit beta-globin-3' UTR was introduced into the genome of albino mice.
      Transgene mRNA was expressed in the retinal pigment epithelium at all ages
      peaking at 4 months. The expression of VEGF protein was increased in both the
      retinal pigment epithelium and choroid. An increase of intravascular adherent
      leukocytes and vessel leakage was observed. Histopathology revealed
      intrachoroidal neovascularization that did not penetrate through an intact
      Bruch's membrane. These results support the hypothesis that additional insults to
      the integrity of Bruch's membrane are required to induce growth of choroidal
      vessels into the subretinal space as seen in age-related macular degeneration.
      This model may be useful to screen for inhibitors of choroidal vessel growth.

PMID- 11238066
TI  - On the importance of standardisation in life sciences.

PMID- 11238065
TI  - Augmented senile plaque load in aged female beta-amyloid precursor protein
      transgenic mice.
AB  - Transgenic mice (Tg2576) overexpressing human beta-amyloid precursor protein with
      the Swedish mutation (APP695SWE) develop Alzheimer's disease-like amyloid beta
      protein (Abeta) deposits by 8 to 10 months of age. These mice show elevated
      levels of Abeta40 and Abeta42, as well as an age-related increase in diffuse and
      compact senile plaques in the brain. Senile plaque load was quantitated in the
      hippocampus and neocortex of 8- to 19-month-old male and female Tg2576 mice. In
      all mice, plaque burden increased markedly after the age of 12 months. At 15 and
      19 months of age, senile plaque load was significantly greater in females than in
      males; in 91 mice studied at 15 months of age, the area occupied by plaques in
      female Tg2576 mice was nearly three times that of males. By enzyme-linked
      immunosorbent assay, female mice also had more Abeta40 and Abeta42 in the brain
      than did males, although this difference was less pronounced than the difference
      in histological plaque load. These data show that senescent female Tg2576 mice
      deposit more amyloid in the brain than do male mice, and may provide an animal
      model in which the influence of sex differences on cerebral amyloid pathology can
      be evaluated.

PMID- 11238063
TI  - Glomeruloid microvascular proliferation follows adenoviral vascular permeability
      factor/vascular endothelial growth factor-164 gene delivery.
AB  - Glomeruloid bodies are a defining histological feature of glioblastoma multiforme
      and some other tumors and vascular malformations. Little is known about their
      pathogenesis. We injected a nonreplicating adenoviral vector engineered to
      express vascular permeability factor/vascular endothelial growth factor-164
      (VPF/VEGF(164)) into the ears of athymic mice. This vector infected local cells
      that strongly expressed VPF/VEGF(164) mRNA for 10 to 14 days, after which
      expression gradually declined. Locally expressed VPF/VEGF(164) induced an early
      increase in microvascular permeability, leading within 24 hours to edema and
      deposition of extravascular fibrin; in addition, many pre-existing microvessels
      enlarged to form thin-walled, pericyte-poor, "mother" vessels. Glomeruloid body
      precursors were first detected at 3 days as focal accumulations of rapidly
      proliferating cells in the endothelial lining of mother vessels, immediately
      adjacent to cells expressing VPF/VEGF(164). Initially, glomeruloid bodies were
      comprised of endothelial cells but subsequently pericytes and macrophages also
      participated. As they enlarged by endothelial cell and pericyte proliferation,
      glomeruloid bodies severely compromised mother vessel lumens and blood flow.
      Subsequently, as VPF/VEGF(164) expression declined, glomeruloid bodies devolved
      throughout a period of weeks by apoptosis and reorganization into normal
      appearing microvessels. These results provide the first animal model for inducing
      glomeruloid bodies and indicate that VPF/VEGF(164) is sufficient for their
      induction and necessary for their maintenance.

PMID- 11238067
TI  - XML, bioinformatics and data integration.
AB  - MOTIVATION: The eXtensible Markup Language (XML) is an emerging standard for
      structuring documents, notably for the World Wide Web. In this paper, the authors
      present XML and examine its use as a data language for bioinformatics. In
      particular, XML is compared to other languages, and some of the potential uses of
      XML in bioinformatics applications are presented. The authors propose to adopt
      XML for data interchange between databases and other sources of data. Finally the
      discussion is illustrated by a test case of a pedigree data model in XML.
      CONTACT: Emmanuel.Barillot@infobiogen.fr

PMID- 11238068
TI  - A hierarchical unsupervised growing neural network for clustering gene expression
      patterns.
AB  - MOTIVATION: We describe a new approach to the analysis of gene expression data
      coming from DNA array experiments, using an unsupervised neural network. DNA
      array technologies allow monitoring thousands of genes rapidly and efficiently.
      One of the interests of these studies is the search for correlated gene
      expression patterns, and this is usually achieved by clustering them. The Self
      Organising Tree Algorithm, (SOTA) (Dopazo,J. and Carazo,J.M. (1997) J. Mol.
      Evol., 44, 226-233), is a neural network that grows adopting the topology of a
      binary tree. The result of the algorithm is a hierarchical cluster obtained with
      the accuracy and robustness of a neural network. RESULTS: SOTA clustering confers
      several advantages over classical hierarchical clustering methods. SOTA is a
      divisive method: the clustering process is performed from top to bottom, i.e. the
      highest hierarchical levels are resolved before going to the details of the
      lowest levels. The growing can be stopped at the desired hierarchical level.
      Moreover, a criterion to stop the growing of the tree, based on the approximate
      distribution of probability obtained by randomisation of the original data set,
      is provided. By means of this criterion, a statistical support for the definition
      of clusters is proposed. In addition, obtaining average gene expression patterns
      is a built-in feature of the algorithm. Different neurons defining the different
      hierarchical levels represent the averages of the gene expression patterns
      contained in the clusters. Since SOTA runtimes are approximately linear with the
      number of items to be classified, it is especially suitable for dealing with huge
      amounts of data. The method proposed is very general and applies to any data
      providing that they can be coded as a series of numbers and that a computable
      measure of similarity between data items can be used. AVAILABILITY: A server
      running the program can be found at: http://bioinfo.cnio.es/sotarray.

PMID- 11238069
TI  - The massively parallel genetic algorithm for RNA folding: MIMD implementation and
      population variation.
AB  - A massively parallel Genetic Algorithm (GA) has been applied to RNA sequence
      folding on three different computer architectures. The GA, an evolution-like
      algorithm that is applied to a large population of RNA structures based on a pool
      of helical stems derived from an RNA sequence, evolves this population in
      parallel. The algorithm was originally designed and developed for a 16384
      processor SIMD (Single Instruction Multiple Data) MasPar MP-2. More recently it
      has been adapted to a 64 processor MIMD (Multiple Instruction Multiple Data) SGI
      ORIGIN 2000, and a 512 processor MIMD CRAY T3E. The MIMD version of the algorithm
      raises issues concerning RNA structure data-layout and processor communication.
      In addition, the effects of population variation on the predicted results are
      discussed. Also presented are the scaling properties of the algorithm from the
      perspective of the number of physical processors utilized and the number of
      virtual processors (RNA structures) operated upon.

PMID- 11238070
TI  - An information-based sequence distance and its application to whole mitochondrial
      genome phylogeny.
AB  - MOTIVATION: Traditional sequence distances require an alignment and therefore are
      not directly applicable to the problem of whole genome phylogeny where events
      such as rearrangements make full length alignments impossible. We present a
      sequence distance that works on unaligned sequences using the information
      theoretical concept of Kolmogorov complexity and a program to estimate this
      distance. RESULTS: We establish the mathematical foundations of our distance and
      illustrate its use by constructing a phylogeny of the Eutherian orders using
      complete unaligned mitochondrial genomes. This phylogeny is consistent with the
      commonly accepted one for the Eutherians. A second, larger mammalian dataset is
      also analyzed, yielding a phylogeny generally consistent with the commonly
      accepted one for the mammals. AVAILABILITY: The program to estimate our sequence
      distance, is available at
      http://www.cs.cityu.edu.hk/~cssamk/gencomp/GenCompress1.htm. The distance
      matrices used to generate our phylogenies are available at
      http://www.math.uwaterloo.ca/~mli/distance.html.

PMID- 11238071
TI  - Automated extraction of information on protein-protein interactions from the
      biological literature.
AB  - MOTIVATION: To understand biological process, we must clarify how proteins
      interact with each other. However, since information about protein-protein
      interactions still exists primarily in the scientific literature, it is not
      accessible in a computer-readable format. Efficient processing of large amounts
      of interactions therefore needs an intelligent information extraction method. Our
      aim is to develop an efficient method for extracting information on protein
      protein interaction from scientific literature. RESULTS: We present a method for
      extracting information on protein-protein interactions from the scientific
      literature. This method, which employs only a protein name dictionary, surface
      clues on word patterns and simple part-of-speech rules, achieved high recall and
      precision rates for yeast (recall = 86.8% and precision = 94.3%) and Escherichia
      coli (recall = 82.5% and precision = 93.5%). The result of extraction suggests
      that our method should be applicable to any species for which a protein name
      dictionary is constructed. AVAILABILITY: The program is available on request from
      the authors.

PMID- 11238072
TI  - GeneOrder: comparing the order of genes in small genomes.
AB  - MOTIVATION: The recent rapid rise in the availability of whole genome DNA
      sequence data has led to bottlenecks in their complete analysis. Specifically,
      there is a need for software tools that will allow mining of gene and putative
      gene data at a whole genome level. These new tools will complement the current
      set already in use for studying specific aspects of individual genes and putative
      genes in detail. A key software challenge is to make them user-friendly, without
      losing their flexibility and capability for use in research. RESULTS: The
      creation of GeneOrder-a web-based interactive, computational tool-allows
      researchers to compare the order of genes in two genomes. It has been tested on
      full genome sequence data for viruses, mitochondria and chloroplasts that were
      obtained from the NCBI GenBank database. It is accessible at
      http://www.bif.atcc.org/GENEOrder/index.html. GeneOrder prepares the comparison
      in table form, listing the order of similar genes. Hyperlinks are provided from
      this output; these lead to the 'Protein Coding Regions' in the NCBI database.

PMID- 11238074
TI  - The art of pedigree drawing: algorithmic aspects.
AB  - MOTIVATION: Giving a meaningful representation of a pedigree is not obvious when
      it includes consanguinity loops, individuals with multiple mates or several
      related families. RESULTS: We show that finding a perfectly meaningful
      representation of a pedigree is equivalent to the interval graph sandwich problem
      and we propose an algorithm for drawing pedigrees.

PMID- 11238073
TI  - ORI-GENE: gene classification based on the evolutionary tree.
AB  - MOTIVATION: Genome projects have produced large amounts of data on the sequences
      of new genes whose functions are as yet unknown. The functions of new genes are
      usually inferred by comparing their sequences with those of known genes, but
      evaluation of the sequence homology of individual genes does not make the most of
      the available sequence information. Therefore, new methods and tools for
      extracting more biological information from homology searches would be
      advantageous. RESULTS: We have developed a computational tool, ORI-GENE, to
      analyze the results of sequence homology searches from the perspective of the
      evolution of selected sets of new genes. ORI-GENE has a graphical interface and
      accomplishes two important tasks: first, based on the output of homology
      searches, it identifies species with similar genes and displays their pattern of
      distribution on the phylogenetic tree. This function enables one to infer the way
      in which a given gene may have propagated among species over time. Second, from
      the distribution patterns, it predicts the point at which a given gene may have
      been first acquired (i.e. its 'origin'), then classifies the gene on that basis.
      Because it makes use of available evolutionary information to show the way in
      which genes cluster among species, ORI-GENE should be an effective tool for the
      screening and classification of new genes revealed by genome analysis.
      AVAILABILITY: ORI-GENE is retrievable via the Internet at:
      http://www.rtc.riken.go.jp/jouhou/ORI-GENE.

PMID- 11238075
TI  - A classification of tasks in bioinformatics.
AB  - MOTIVATION: This paper reports on a survey of bioinformatics tasks currently
      undertaken by working biologists. The aim was to find the range of tasks that
      need to be supported and the components needed to do this in a general query
      system. This enabled a set of evaluation criteria to be used to assess both the
      biology and mechanical nature of general query systems. RESULTS: A classification
      of the biological content of the tasks gathered offers a checklist for those
      tasks (and their specialisations) that should be offered in a general
      bioinformatics query system. This semantic analysis was contrasted with a
      syntactic analysis that revealed the small number of components required to
      describe all bioinformatics questions. Both the range of biological tasks and
      syntactic task components can be seen to provide a set of bioinformatics
      requirements for general query systems. These requirements were used to evaluate
      two bioinformatics query systems.

PMID- 11238076
TI  - Distribution of genes for lysine biosynthesis through the aminoadipate pathway
      among prokaryotic genomes.
AB  - Deinococcus radioduranshas homologous genes to the genes which from the Thermus:
      thermophilus gene cluster for lysine biosynthesis. Interestingly, those genes are
      clustered in Thermus, nevertheless they are scattered in Deinococcus. A similar
      gene cluster has only been found in Pyrococcus However, the phylogenetic analyses
      indicated that the deduced gene products from Deinococcus were the most closely
      related to the proteins encoded in the Thermus gene cluster for lysine
      biosynthesis. Therefore, those genes had not been transferred horizontally
      between Pyrococcus and Thermus. It is strongly suggested that a common ancestor
      of Deinococcus and Thermus possessed the genes for lysine biosynthesis through
      the aminoadipate pathway. These had been clustered through the evolution of
      Thermus or had been scattered from the gene cluster through the evolution of
      Deinococcus. In addition, I showed that LysW and its homologues were specialized
      proteins for the prokaryotic lysine biosynthesis through the aminoadipate
      pathway.

PMID- 11238077
TI  - Virtual PCR.
AB  - We present an algorithm that uses public sequence data to predict PCR products.
      The algorithm is implemented as a CGI script. Output is compared to real-world
      PCR. AVAILABILITY: Perl code and instructions for installation are freely
      available over the internet at http://www.sci.muni.cz/LMFR/vpcr.html.

PMID- 11238078
TI  - Using clusters of computers for large QU-GENE simulation experiments.
AB  - The QU-GENE Computing Cluster (QCC) is a hardware and software solution to the
      automation and speedup of large QU-GENE (QUantitative GENEtics) simulation
      experiments that are designed to examine the properties of genetic models,
      particularly those that involve factorial combinations of treatment levels. QCC
      automates the management of the distribution of components of the simulation
      experiments among the networked single-processor computers to achieve the
      speedup.

PMID- 11238079
TI  - MOSAIC: segmenting multiple aligned DNA sequences.
AB  - MOSAIC is a set of tools for the segmentation of multiple aligned DNA sequences
      into homogeneous zones. The segmentation is based on the distribution of
      mutational events along the alignment. As an example, the analysis of one
      repeated sequence belonging to the subtelomeric regions of the yeast genome is
      presented. AVAILABILITY: Free access from
      ftp://ftp.biomath.jussieu.fr/pub/papers/MOSAIC

PMID- 11238080
TI  - COMBOSA3D: combining sequence alignments with three-dimensional structures.
AB  - COMBOSA3D is a program that allows sequence conservation to be viewed in its
      proper three-dimensional environment. It superimposes sequence alignment
      information onto a protein structure using a customizable color scheme, which is
      also applied to a textual sequence alignment for reference. AVAILABILITY: The
      program can be tested at http://www.bioinformatics.org/combosa3d/, and the source
      code is freely available.

PMID- 11238081
TI  - 3Dee: a database of protein structural domains.
AB  - The 3Dee database is a repository of protein structural domains. It stores
      alternative domain definitions for the same protein, organises domains into
      sequence and structural hierarchies, contains non-redundant set(s) of sequences
      and structures, multiple structure alignments for families of domains, and allows
      previous versions of the database to be regenerated. AVAILABILITY: 3Dee is
      accessible on the World Wide Web at the URL
      http://barton.ebi.ac.uk/servers/3Dee.html.

PMID- 11238082
TI  - RCNPRED: prediction of the residue co-ordination numbers in proteins.
AB  - The RCNPRED server implements a neural network-based method to predict the co
      ordination numbers of residues starting from the protein sequence. Using
      evolutionary information as input, RCNPRED predicts the residue states of the
      proteins in the database with 69% accuracy and scores 12 percentage points higher
      than a simple statistical method. Moreover the server implements a neural network
      to predict the relative solvent accessibility of each residue. A protein sequence
      can be directly submitted to RCNPRED: residue co-ordination numbers and solvent
      accessibility for each chain are returned via e-mail. AVAILABILITY: Freely
      available to non-commercial users at http://prion.biocomp.unibo.it/rcnpred.html.

PMID- 11238086
TI  - Interleukin-7 restores immunity in athymic T-cell-depleted hosts.
AB  - Thymic-deficient hosts rely primarily on antigen-driven expansion to restore the
      peripheral T-cell compartment following T-cell depletion (TCD). The degree to
      which this thymic-independent pathway can restore immune competence remains
      poorly understood but has important implications for a number of clinical
      conditions including stem cell transplantation and human immunodeficiency virus
      (HIV) infection. A model of HY-mediated skin graft rejection by athymic, TCD mice
      was used to show that restoration of naive and recall responses via peripheral
      expansion requires transfer of only 25 x 10(6) lymph node (LN) cells representing
      approximately 10% of the T-cell repertoire. Constitutive expression of bcl-2 in
      the expanding inocula restored recall responses to HY at a substantially lower LN
      cell dose (1 x 10(6)), which is normally insufficient to induce HY-mediated graft
      rejection in athymic hosts. Interestingly, bcl-2 had no effect on primary
      responses. Interleukin-7 (IL-7) potently enhanced thymic-independent peripheral
      expansion and led to HY graft rejection using an LN cell dose of 1 x 10(6) in
      both primary and recall models. The restoration of immune competence by IL-7
      appeared to be mediated through a combination of programmed cell death
      inhibition, improved costimulation, and modulation of antigen-presenting cell
      (APC) function. These results show that immune competence for even stringent
      antigens such as HY can be restored in the absence of thymic function and
      identify IL-7 as a potent modulator of thymic-independent T-cell regeneration.

PMID- 11238087
TI  - Rapid mobilization of murine hematopoietic stem cells with enhanced engraftment
      properties and evaluation of hematopoietic progenitor cell mobilization in rhesus
      monkeys by a single injection of SB-251353, a specific truncated form of the
      human CXC chemokine GRObeta.
AB  - SB-251353 is an N-terminal truncated form of the human CXC chemokine GRObeta.
      Recombinant SB-251353 was profiled in murine and rhesus monkey peripheral blood
      stem cell mobilization and transplantation models. SB-251353 rapidly and
      transiently mobilized hematopoietic stem cells and neutrophils into the
      peripheral blood after a single subcutaneous injection. Transplantation of
      equivalent numbers of hematopoietic stem cells mobilized by SB-251353 into
      lethally irradiated mice resulted in faster neutrophil and platelet recovery than
      stem cells mobilized by granulocyte colony-stimulating factor (G-CSF). A single
      injection of SB-251353 in combination with 4 days of G-CSF administration
      resulted in augmented stem and progenitor cell mobilization 5-fold greater than G
      CSF alone. Augmented stem cell mobilization could also be demonstrated in mice
      when a single injection of SB-251353 was administered with only one-day treatment
      with G-CSF. In addition, SB-251353, when used as a single agent or in combination
      with G-CSF, mobilized long-term repopulating stem cells capable of hematopoietic
      reconstitution of lethally irradiated mice. In rhesus monkeys, a single injection
      of SB-251353 induced rapid increases in peripheral blood hematopoietic progenitor
      cells at a 50-fold lower dose than in mice, which indicates a shift in potency.
      These studies provide evidence that the use of SB-251353 alone or in combination
      with G-CSF mobilizes hematopoietic stem cells with long-term repopulating
      ability. In addition, this treatment may (1) reduce the number of apheresis
      sessions and/or amount of G-CSF required to collect adequate numbers of
      hematopoietic stem cells for successful peripheral blood cell transplantation and
      (2) improve hematopoietic recovery after transplantation.

PMID- 11238088
TI  - CC chemokines and the receptors CCR3 and CCR5 are differentially expressed in the
      nonneoplastic leukocytic infiltrates of Hodgkin disease.
AB  - Lymph nodes with Hodgkin disease (HD) harbor few neoplastic cells in a marked
      leukocytic infiltrate. Since chemokines are likely to be involved in the
      recruitment of these leukocytes, the expression of potentially relevant
      chemokines and chemokine receptors were studied in lymph nodes from 24 patients
      with HD and in 5 control lymph nodes. The expression of regulated on activation,
      normal T cell expressed and secreted (RANTES), monocyte chemotactic protein (MCP)
      1, macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta was analyzed by in
      situ hybridization and that of CCR3 and CCR5 by immunohistochemistry and flow
      cytometry. It was found that, overall, the expression of all 4 chemokines was
      markedly enhanced, but the cellular source was different. RANTES was expressed
      almost exclusively by T cells whereas the expression of MCP-1, MIP-1alpha, and
      MIP-1beta was confined largely to macrophages. In control lymph nodes, chemokine
      expression was low, with the exception of MIP-1alpha in macrophages. CCR3 and
      CCR5 were highly expressed in T cells of HD involved but not of control lymph
      nodes. CCR3 was equally distributed in CD4+ and CD8+ cells, but CCR5 was
      associated largely with CD4+ cells. In HD lymph nodes, CCR3 and CCR5 were also
      expressed in B cells, which normally do not express these receptors. All these
      chemokines and receptors studied, by contrast, were absent in the neoplastic
      cells. It was concluded that chemokines are involved in the formation of the HD
      nonneoplastic leukocytic infiltrate. Expression of CCR3 and CCR5 appears to be
      characteristic of HD, but the roles of these receptors' up-regulation for the
      disease process remain unclear.

PMID- 11238089
TI  - Characterization of a novel autosomal dominant bleeding disorder in a large
      kindred from east Texas.
AB  - A large east Texas family with autosomal dominant inheritance of a novel bleeding
      disorder has been identified. The disorder is characterized clinically by easy
      bruising, life-threatening bleeding with trauma or surgery, and menorrhagia in
      affected women. Laboratory studies demonstrated prolongation of the prothrombin
      time and activated partial thromboplastin time in affected individuals.
      Paradoxically, assays of known coagulation factors are all within normal limits.
      To determine the molecular basis of this disease, a candidate gene linkage
      analysis in this kindred was done. Initially it was hypothesized that the cause
      of the disease in this family could be an antithrombin III (AT3) mutation that
      resulted in a constitutively active AT3 in the absence of heparin binding.
      Linkage studies using DNA from the family and an intragenic polymorphic marker
      within the AT3 gene showed that the disease mapped to this locus. The coding
      region and intron/exon junctions of AT3 were sequenced using the proband's DNA,
      but this analysis failed to identify a mutation. Additional family members were
      recruited for the study, and 16 polymorphic markers around the AT3 gene were
      analyzed. Using 2 recombinants, the critical interval for the defective gene was
      narrowed to approximately 1.5 Mb, centromeric to AT3. The factor V (FV) gene was
      mapped into the disease interval and sequenced; there were no mutations found.
      Elucidation of the genetic defect causing the bleeding disorder in this family
      may reveal a novel protein involved in the coagulation cascade.

PMID- 11238090
TI  - The effect of antiviral therapy on t(14;18) translocation and immunoglobulin gene
      rearrangement in patients with chronic hepatitis C virus infection.
AB  - The mechanism of lymphomagenesis of hepatitis C virus (HCV)-related B-cell
      lymphoma is unknown. Recently, it has been suggested that HCV may induce B-cell
      clonal proliferation and t(14;18) translocation in patients chronically infected
      with the virus. Thus, this study investigated the effect of antiviral treatment
      on immunoglobulin heavy-chain gene (IgH) rearrangement and t(14;18) translocation
      in HCV infected patients. Twenty-nine patients with chronic HCV infection were
      studied in whom IgH rearrangement and/or t(14;18) translocation were previously
      detected. The IgH rearrangement (FR3/JH) and t(14;18) translocation (MBR bcl2-JH)
      were detected in peripheral blood mononuclear cells by polymerase chain reaction.
      Fifteen of 29 patients (8 with IgH rearrangement, 6 with t(14;18) translocation,
      and 1 with both) were treated with either interferon-alpha or by combination
      therapy with interferon and ribavirin for 6 to 12 months. IgH rearrangement
      became negative in 7 of 9 treated patients compared with only 1 of 8 of
      nontreated patients (P <.02). The t(14;18) translocation became negative in 6 of
      7 treated patients compared with 1 of 6 nontreated patients (P =.03).
      Disappearance of IgH rearrangement or t(14;18) translocation was strongly
      associated with virologic response to treatment. Two t(14;18)+ patients developed
      B-cell lymphoma during follow-up. Antiviral treatment appears to be effective in
      eliminating the clonal proliferation of B cells in patients with chronic HCV
      infection and may prevent the subsequent development of lymphoma. The mechanism
      can be related to a direct effect of interferon-alpha on the proliferating clone
      or to an indirect effect by eradicating the antigenic stimulus.

PMID- 11238091
TI  - Early detection of BCR-ABL transcripts by quantitative reverse transcriptase
      polymerase chain reaction predicts outcome after allogeneic stem cell
      transplantation for chronic myeloid leukemia.
AB  - The reverse transcriptase-polymerase chain reaction (RT-PCR) has become widely
      used for monitoring minimal residual disease after allogeneic stem cell
      transplantation (SCT) for chronic myeloid leukemia (CML). However, most of these
      studies were performed using qualitative RT-PCR, and the interpretation of the
      results obtained has been conflicting. The correlation of a quantitative RT-PCR
      test performed early after SCT (at 3 to 5 months) and long-term outcome of CML
      patients surviving for more than 6 months was studied. Between January 1991 and
      June 1999, data from 138 CML patients who received allografts were evaluated.
      Early RT-PCR results were classified as (1) negative if there were no BCR-ABL
      transcripts detected (n = 61), (2) positive at low level if the total number of
      BCR-ABL transcripts was less than 100 per microg RNA and/or the BCR-ABL/ABL ratio
      was less than 0.02% (n = 14), or (3) positive at high level if transcript levels
      exceeded the thresholds defined above (n = 63). Three years after SCT the
      cumulative incidence of relapse was 16.7%, 42.9%, and 86.4%, respectively (P
      =.0001). The relationship between BCR-ABL transcript level and probability of
      relapse was apparent whether patients had received sibling or unrelated donor SCT
      and also whether or not the transplantation was T cell depleted. The results
      suggest that quantitative RT-PCR performed early after SCT is useful for
      predicting outcome and may help to define the need for further treatment.

PMID- 11238092
TI  - Chromosome 13 abnormalities identified by FISH analysis and serum beta2
      microglobulin produce a powerful myeloma staging system for patients receiving
      high-dose therapy.
AB  - A careful prognostic evaluation of patients referred for high-dose therapy (HDT)
      is warranted to identify those who maximally benefit from HDT as well as those
      who clearly fail current HDT and are candidates for more innovative treatments.
      In a series of 110 patients with myeloma who received HDT as first-line therapy,
      times to event (disease progression and death) were studied through proportional
      hazard models, in relation to different prognostic factors, including a
      chromosome 13 fluorescence in situ hybridization (FISH) analysis using a D13S319
      probe. Delta13 was detected in 42 patients (38%). Follow-up time among surviving
      patients and survival time were 48 +/- 3 and 51 +/- 7 months, respectively
      (median +/- SE). In the univariate analysis, Delta13 was the most powerful
      adverse prognostic factor for all times to event, especially for the survival
      time (P <.0001) and was followed by beta2-microglobulin (beta2m) levels 2.5 mg/L
      or higher (P =.0001). The comparison of survival prognostic models including
      beta2m 2.5 mg/L or greater and another factor favored the Delta13/beta2m
      combination. In 22 patients (20%) with no unfavorable factor, the median survival
      time was not reached at 111 months. In contrast, among 55 patients (50%) with one
      unfavorable factor and 33 patients (30%) with 2 unfavorable factors, median
      survival times were 47.3 +/- 4.6 months and 25.3 +/- 3.2 months, respectively (P
      <.0001). We conclude that delta13, adequately detected by FISH analysis, is a
      very strong factor related to poor survival, especially when associated with a
      beta2m level of 2.5 mg/L or higher. Routine FISH Delta13 assessment is strongly
      recommended for patients considered for HDT.

PMID- 11238093
TI  - Unrelated marrow transplantation for adult patients with poor-risk acute
      lymphoblastic leukemia: strong graft-versus-leukemia effect and risk factors
      determining outcome.
AB  - Between 1988 and 1999, 127 patients with poor-risk acute lymphoblastic leukemia
      (ALL) received a matched unrelated donor transplant using marrow procured by
      National Marrow Donor Program (NMDP) collection centers and sent out to 46
      transplant centers worldwide. Poor risk was defined by the presence of the
      translocations t(9;22) (n = 97), or t(4;11) (n = 25), or t(1;19) (n = 5). Sixty
      four patients underwent transplantation in first remission (CR1), 16 in CR2 or
      CR3, and 47 patients had relapsed ALL or primary induction failure (PIF). Overall
      survival at 2 years from transplant was 40% for patients in CR1, 17% in CR2/3,
      and 5% in PIF or relapse. Treatment-related mortality (TRM) and relapse
      mortality, estimated as competing risk factors, were 54% and 6%, respectively, in
      CR1, 75% and 8% in CR2/3, and 64% and 31% in PIF or relapse. Currently 23 CR1
      patients are alive and free of disease with a median follow-up of 24 months
      (range, 3-97). Multivariable analysis showed that CR1, shorter interval from
      diagnosis to transplantation, DRB1 match, negative cytomegalovirus (CMV) serology
      (patient and donor), and presence of the Philadelphia chromosome, t(9;22), were
      independently associated with better disease-free survival (DFS). Transplantation
      in CR and presence of t(9;22) were associated with lower risk of relapse. Shorter
      interval from diagnosis to transplantation, DRB1-match, negative CMV, higher
      marrow cell dose, and Karnofsky score of 90 or higher were associated with less
      TRM. These results indicate that, despite a relatively high TRM, the low relapse
      rate resulted in a 37% +/- 13% DFS for CR1 patients, comparing favorably to
      results obtained with chemotherapy alone and matching results following HLA
      identical sibling transplantation.

PMID- 11238094
TI  - Mechanisms of granulocytosis in the absence of CD18.
AB  - Genetic deficiency in CD18 leads to disease characterized by myeloid hyperplasia,
      including profound granulocytosis and splenomegaly. Myeloid hyperplasia could
      directly result from the disruption of CD18 functions essential to granulopoiesis
      or basal leukocyte trafficking. Alternatively, myeloid hyperplasia could be
      reactive in nature, due to disruption of essential roles of CD18 in leukocyte
      responses to microbial challenge. To distinguish between these mechanisms, the
      hematopoietic systems of lethally irradiated wild-type (WT) mice were
      reconstituted with either WT fetal liver cells or CD18-deficient fetal liver
      cells, or an equal mixture of both types of cells. Granulocytosis and
      splenomegaly developed in mice that received CD18-deficient fetal liver cells.
      Splenomegaly was prevented and granulocytosis was inhibited by more than 95% in
      mice that had received both CD18-deficient and WT fetal liver cells, suggesting
      that myeloid hyperplasia was largely reactive in nature. Consistent with this
      postulate, the circulating life spans in the blood and the fraction of
      neutrophils that incorporated BrdU in the bone marrow were not increased for CD18
      deficient neutrophils compared with the WT. However, these animals did develop
      mild granulocytosis compared with mice reconstituted with WT cells alone, and a
      higher percentage of CD18-deficient leukocytes were neutrophils compared with the
      WT leukocytes. These observations suggest that the granulocytosis observed in the
      absence of CD18 occurs through at least 2 mechanisms: one that is dramatically
      improved by the presence of WT cells, likely reactive in nature, and a second
      that is independent of the WT hematopoietic cells, involving an alteration in the
      lineage distribution of blood leukocytes.

PMID- 11238095
TI  - Endothelial dysfunction in patients with sickle cell disease is related to
      selective impairment of shear stress-mediated vasodilation.
AB  - Interactions between the endothelium and erythrocytes may contribute to the
      vascular complications of sickle cell disease (SCD). Endothelium-derived nitric
      oxide (NO) plays a major role in the regulation of vasomotor tone in response to
      wall shear stress (WSS) variations and pharmacologic stimuli. However, little is
      known about endothelial NO production in patients with steady-state SCD. We
      investigated endothelial NO production in response to flow or vasoactive agonists
      in 16 homozygous patients with steady-state SCD and 15 controls. Flow-mediated
      dilation (FMD), arterial diameter changes in response to 100% oxygen inhalation,
      blood viscosity, and calculated WSS were determined in all patients and controls.
      At baseline, WSS was higher in SCD patients than in controls, whereas arterial
      diameter was similar. In patients with SCD, FMD was impaired (1.73% +/- 0.44% vs
      3.97% +/- 0.24% in the controls, P <.001) and vasoconstriction in response to
      100% oxygen was abolished. Using venous occlusion plethysmography, forearm blood
      flow (FBF) was evaluated in response to acetylcholine, nitro-monomethyl-L
      arginine (L-NMMA), and sodium nitroprusside (SNP) in subgroups of 9 controls and
      7 patients with SCD. Acetylcholine induced a significantly greater FBF increase
      in the patients (9.7 +/- 2.9 mL/min/100 mL of forearm volume vs 2.5 +/- 1.5
      mL/min/100 mL in the controls, P <.001), whereas responses to L-NMMA and SNP were
      similar. These results suggest that endothelial dysfunction may prevent the
      arterial diameter of patients with SCD from adapting to chronic or acute shear
      stress elevations. This may contribute to the pathophysiology of vaso-occlusive
      crisis in patients with SCD.

PMID- 11238096
TI  - Treatment of B-lymphoproliferative disorder with a monoclonal anti-interleukin-6
      antibody in 12 patients: a multicenter phase 1-2 clinical trial.
AB  - Severe T-cell immunodeficiency after solid organ or bone marrow transplantation
      may result in the uncontrolled outgrowth of latently Epstein-Barr virus-infected
      B cells, leading to B-lymphoproliferative disorder (BLPD). Given the potentially
      important pathogenic role of IL-6 in BLPD, it was tested whether the in vivo
      neutralization of IL-6 by a monoclonal anti-IL-6 antibody could contribute to the
      control of BLPD. Safety and efficacy were assessed in 12 recipients of
      transplanted organs who had BLPD refractory to the reduction of immunosuppression
      over 8 days. Five patients received 0.4 mg/kg per day. The next 7 patients
      received 0.8 mg/kg per day. Treatment was scheduled to last 15 days. It was
      completed in 10 patients, and in the other 2 patients was discontinued early
      (days 10 and 13, respectively) because of disease progression. Treatment
      tolerance was good, and no major side effects were observed. High C-reactive
      protein levels were found in 9 patients before treatment but were normalized
      under treatment in all patients, demonstrating efficient IL-6 neutralization.
      Complete remission (CR) was observed in 5 patients and partial remission (PR) in
      3 patients. Relapse was observed in 1 of these 8 patients in whom remission was
      observed. This relapse was unresponsive to treatment. Disease was stable in 1
      patient, but it progressed in 3 patients. Seven patients are alive and well. Two
      patients died because of disease progression, and 3 patients died while in CR
      (chronic rejection in 2 patients and BLPD sequelae in 1 patient). These data
      suggest that the anti-IL-6 antibody is safe and should be further explored in the
      treatment of BLPD.

PMID- 11238097
TI  - Impact of donor type on outcome of bone marrow transplantation for Wiskott
      Aldrich syndrome: collaborative study of the International Bone Marrow Transplant
      Registry and the National Marrow Donor Program.
AB  - Human leukocyte antigen (HLA)-identical sibling bone marrow transplantation is an
      effective treatment for Wiskott-Aldrich syndrome. However, most children with
      this disease lack such donors and many patients receive transplants from
      alternative donors. This study compared outcomes of HLA-identical sibling, other
      related donor, and unrelated donor transplantation for Wiskott-Aldrich syndrome.
      The outcome of 170 transplantations for Wiskott-Aldrich syndrome, from 1968 to
      1996, reported to the International Bone Marrow Transplant Registry and/or
      National Marrow Donor Program were assessed. Fifty-five were from HLA-identical
      sibling donors, 48 from other relatives, and 67 from unrelated donors.
      Multivariate proportional hazards regression was used to compare outcome by donor
      type and identify other prognostic factors. Most transplant recipients were
      younger than 5 years (79%), had a pretransplantation performance score greater
      than or equal to 90% (63%), received pretransplantation preparative regimens
      without radiation (82%), and had non-T-cell-depleted grafts (77%). Eighty percent
      received their transplant after 1986. The 5-year probability of survival (95%
      confidence interval) for all subjects was 70% (63%-77%). Probabilities differed
      by donor type: 87% (74%-93%) with HLA-identical sibling donors, 52% (37%-65%)
      with other related donors, and 71% (58%-80%) with unrelated donors (P =.0006).
      Multivariate analysis indicated significantly lower survival using related donors
      other than HLA-identical siblings (P =.0004) or unrelated donors in boys older
      than 5 years (P =.0001), compared to HLA-identical sibling transplants. Boys
      receiving an unrelated donor transplant before age 5 had survivals similar to
      those receiving HLA-identical sibling transplants. The best transplantation
      outcomes in Wiskott-Aldrich syndrome are achieved with HLA-identical sibling
      donors. Equivalent survivals are possible with unrelated donors in young
      children.

PMID- 11238098
TI  - Screening for circulating galactomannan as a noninvasive diagnostic tool for
      invasive aspergillosis in prolonged neutropenic patients and stem cell
      transplantation recipients: a prospective validation.
AB  - The diagnosis of invasive aspergillosis (IA) in patients with hematologic
      disorders is not straightforward; lack of sensitive and specific noninvasive
      diagnostic tests remains a major obstacle for establishing a precise diagnosis.
      In a series of 362 consecutive high-risk treatment episodes that were stratified
      according to the probability of IA based on recently accepted case definition
      sets, the potential for diagnosis of serial screening for circulating
      galactomannan (GM), a major aspergillar cell wall constituent was validated.
      After incorporating postmortem findings to allow a more accurate final analysis,
      this approach proved to have a sensitivity of 89.7% and a specificity of 98.1%.
      The positive and negative predictive values equaled 87.5% and 98.4%,
      respectively. False-positive reactions occurred at a rate of 14%, although this
      figure might be overestimated due to diagnostic uncertainty. More or less
      stringent criteria of estimation could highly influence sensitivity, which ranged
      from 100% to 42%; the impact on other test statistics was far less dramatic. All
      proven cases of IA, including 23 cases confirmed after autopsy only, had been
      detected before death, although serial sampling appeared to be necessary to
      maximize detection. The excellent sensitivity and negative predictive value makes
      this approach suitable for clinical decision making. Unfortunately, given the
      species-specificity of the assay, some emerging non-Aspergillus mycoses were not
      detected. In conclusion, serial screening for GM, complemented by appropriate
      imaging techniques, is a sensitive and noninvasive tool for the early diagnosis
      of IA in high-risk adult hematology patients.

PMID- 11238099
TI  - Adenovirus-mediated expression of a mutant IkappaB kinase 2 inhibits the response
      of endothelial cells to inflammatory stimuli.
AB  - In a variety of cell types, the transcription factor nuclear factor kappaB (NF
      kappaB) functions as a mediator of stress and immune responses. In endothelial
      cells (ECs), it controls the expression of genes encoding, eg, cytokines, cell
      adhesion molecules, and procoagulatory proteins. This study investigates the
      effect of NF-kappaB suppression on several pathophysiologic functions of ECs,
      including inflammation, coagulation, and angiogenesis. A recombinant adenovirus
      was generated for expression of a dominant negative (dn) mutant of IkappaB kinase
      2 (IKK2), a kinase that acts as an upstream activator of NF-kappaB. dnIKK2
      inhibited NF-kappaB, resulting in strongly reduced nuclear translocation and DNA
      binding activity of the transcription factor and lack of expression of several
      proinflammatory markers, including E-selectin, intercellular adhesion molecule 1,
      vascular cell adhesion molecule 1, and interleukin-8. Concomitantly, inhibition
      of leukocyte binding to dnIKK2-expressing ECs could be demonstrated in a cell
      adhesion assay. Furthermore, expression of tissue factor as well as the ability
      to form capillary tubes in a matrigel assay was impaired in dnIKK2-expressing
      ECs. These data demonstrate that NF-kappaB is of central importance not only for
      the inflammatory response but also for a number of other EC functions. Therefore,
      this transcription factor as well as its upstream regulatory signaling molecules
      may represent favorable targets for therapeutic interference.

PMID- 11238100
TI  - Lack of dominant-negative effects of a truncated gamma(c) on retroviral-mediated
      gene correction of immunodeficient mice.
AB  - A recent clinical trial of gene therapy for X-linked severe combined
      immunodeficiency (XSCID) has shown that retroviral-mediated gene correction of
      bone marrow stem cells can lead to the development of normal immune function.
      These exciting results have been preceded by successful immune reconstitution in
      several XSCID mouse models, all carrying null mutations of the common gamma chain
      (gamma(c)). One question not formally addressed by these previous studies is that
      of possible dominant-negative effects of the endogenous mutant gamma(c) protein
      on the activity of the wild-type transferred gene product. The present work was
      therefore undertaken to study whether corrective gene transfer was applicable to
      an XSCID murine model with preserved expression of a truncated gammac molecule
      (Deltagamma(c+)-XSCID). Gene correction of Deltagamma(c+)-XSCID mice resulted in
      the reconstitution of lymphoid development, and preferential repopulation of
      lymphoid organs by gene-corrected cells demonstrated the selective advantage of
      gamma(c)-expressing cells in vivo. Newly developed B cells showed normalization
      of lipopolysaccharide-mediated proliferation and interleukin-4 (IL-4)-induced
      immunoglobulin G1 isotype switching. Splenic T cells and thymocytes of treated
      animals proliferated normally to mitogens and responded to the addition of IL-2,
      IL-4, and IL-7, indicating functional reconstitution of gammac-sharing receptors.
      Repopulated thymi showed a clear increase of CD4-/CD8- and CD8+ fractions, both
      dramatically reduced in untreated Deltagamma(c+)-XSCID mice. These improvements
      were associated with the restoration of Bcl-2 expression levels and enhanced cell
      survival. These data indicate that residual expression of the endogenous
      truncated gamma(c) did not lead to dominant-negative effects in this murine model
      and suggest that patient selection may not be strictly necessary for gene therapy
      of XSCID.

PMID- 11238101
TI  - In utero transplantation of fetal liver cells in the mucopolysaccharidosis type
      VII mouse results in low-level chimerism, but overexpression of beta
      glucuronidase can delay onset of clinical signs.
AB  - Mice with the lysosomal storage disease mucopolysaccharidosis (MPS) VII, caused
      by a deficiency of beta-glucuronidase (GUSB), have signs of disease present at
      birth. Bone marrow transplantation (BMT) or retroviral vector-mediated gene
      transfer into hematopoietic stem cells can partially correct the disease in adult
      mice, and BMT performed at birth results in a better clinical outcome. Thus,
      treatment in utero may result in further improvement. However, this must be done
      without cyto-ablation, and the donor cells do not have a competitive repopulating
      advantage over host cells. Transplantation in utero of either syngeneic fetal
      liver hematopoietic stem cells marked with a retroviral vector, or allogeneic
      donor cells that constitutively express high levels of human GUSB from a
      transgene, resulted in only about 0.1% engraftment in the adult. Immuno-affinity
      enrichment of stem and progenitor cells of 5- to 10-fold resulted in
      significantly higher GUSB activities at 2 months of age, but by 6 months
      engraftment was about 0.1%. Attempts to further increase the number of stem and
      progenitor cells were deleterious to the recipients. Nevertheless, GUSB expressed
      during the first 2 months of life in MPS VII fetuses could delay the onset of
      overt signs of disease. This suggests that the expression of some normal enzyme
      activity beginning in fetal life may offer the possibility of slowing the
      progression of the disease until more definitive postnatal transplantation or
      gene transfer to stem cells could be accomplished.

PMID- 11238102
TI  - Xenotransplantation of immunodeficient mice with mobilized human blood CD34+
      cells provides an in vivo model for human megakaryocytopoiesis and platelet
      production.
AB  - The study of megakaryocytopoiesis has been based largely on in vitro assays. We
      characterize an in vivo model of megakaryocyte and platelet development in which
      human peripheral blood stem cells (PBSCs) differentiate along megakaryocytic as
      well as myeloid/lymphoid lineages in sublethally irradiated nonobese
      diabetic/severe combined immunodeficient (NOD-SCID) mice. Human hematopoiesis
      preferentially occurs in the bone marrow of the murine recipients, and
      engraftment is independent of exogenous cytokines. Human colony-forming units
      megakaryocyte (CFU-MK) develop predominantly in the bone marrow, and their
      presence correlates with the overall degree of human cell engraftment. Using a
      sensitive and specific flow cytometric assay, human platelets are detected in the
      peripheral blood from weeks 1 to 8 after transplantation. The number of
      circulating human platelets peaks at week 3 with a mean of 20 x 10(9)/L. These
      human platelets are functional as assessed by CD62P expression in response to
      thrombin stimulation in vitro. Exogenous cytokines have a detrimental effect on
      CFU-MK production after 2 weeks, and animals treated with these cytokines have no
      circulating platelets 8 weeks after transplantation. Although cytokine
      stimulation of human PBSCs ex vivo led to a significant increase in CFU-MK,
      CD34+/41+, and CD41+ cells, these ex vivo expanded cells provided only delayed
      and transient platelet production in vivo, and no CFU-MK developed in vivo after
      transplantation. In conclusion, xenogeneic transplantation of human PBSCs into
      NOD/SCID mice provides an excellent in vivo model to study human
      megakaryocytopoiesis and platelet production.

PMID- 11238103
TI  - Role of double-stranded RNA-dependent protein kinase in mediating
      hypersensitivity of Fanconi anemia complementation group C cells to interferon
      gamma, tumor necrosis factor-alpha, and double-stranded RNA.
AB  - Hematopoietic cells bearing inactivating mutations of Fanconi anemia group C
      (FANCC) are excessively apoptotic and demonstrate hypersensitivity not only to
      cross-linking agents but also to interferon gamma (IFN-gamma) and tumor necrosis
      factor-alpha. Seeking essential signaling pathways for this phenotype, this study
      quantified constitutive and induced RNA-dependent protein kinase (PKR) activation
      in Fanconi anemia cells of the C complementation group (FA-C). PKR was
      constitutively phosphorylated and exhibited an increased binding affinity for
      double-stranded RNA (dsRNA) in FANCC(-/-) cells. FANCC(-/-) cells were
      hypersensitive to both dsRNA and the combination of dsRNA and IFN-gamma in that
      these agents induced a higher fraction of apoptosis in FANCC(-/-) cells than in
      normal cells. Overexpression of wild-type PKR-sensitized FANCC(-/-) cells to
      apoptosis induced by IFN-gamma and dsRNA. Conversely, inhibition of PKR function
      by enforced expression of a dominant-negative inhibitory mutant of PKR
      (PKRDelta6) substantially reduced the IFN and dsRNA hypersensitivity of FANCC(-/
      ) cells. Two PKR target molecules, IkappaB-alpha and IRF-1, were not
      differentially activated in FANCC(-/-) cells, but enforced expression of a
      nonphosphorylatable form of eukaryotic translation initiation factor-2alpha
      reversed the PKR-mediated block of messenger RNA translation and partially
      abrogated the PKR-mediated apoptosis in FANCC(-/-) cells. Because no evidence was
      found of a PKR/FANCC complex in normal cells, it was concluded that an essential
      function of FANCC is to suppress, indirectly, the activity of PKR and that FANCC
      inactivation results in IFN hypersensitivity, at least in part, because this
      function of FANCC is abrogated.

PMID- 11238104
TI  - Characterization of Mpl mutants using primary megakaryocyte-lineage cells from
      mpl(-/-) mice: a new system for Mpl structure-function studies.
AB  - Mpl is the thrombopoietin (TPO) receptor. The current molecular understanding of
      how Mpl activation stimulates proliferation of megakaryocyte-lineage cells is
      based largely on the engineered expression of Mpl in nonmegakaryocyte-lineage
      cell lines. However, the relevance of these findings to Mpl signaling in primary
      megakaryocyte-lineage cells remains largely unknown. Therefore, a system was
      developed to study Mpl function in primary mpl(-/-) megakaryocyte-lineage cells.
      Expressing avian retroviral receptors on the surfaces of mammalian cells
      overcomes their natural block to avian retroviral infection; 815 bp of human
      GPIIb regulatory sequence was used to generate transgenic mice with megakaryocyte
      lineage expression of the subgroup A avian leukosis virus receptor, TVA. Avian
      retroviral infection of unfractionated bone marrow from these mice is restricted
      to megakaryocyte-lineage cells. The transgenic mice were crossed to an mpl(-/-)
      background generating GPIIb-tva+mpl(-/-) mice. By using avian retroviruses to
      express wild-type or mutant Mpl on the surfaces of primary megakaryocyte-lineage
      cells, it was demonstrated that (1) the 10 membrane-proximal, cytoplasmic amino
      acids of Mpl are required for TPO-induced proliferation; (2) Y582F mutation
      confers a proliferative advantage over wild-type Mpl and imparts a constitutive
      anti-apoptotic signal; (3) truncating the 50 C-terminal Mpl amino acids reduces
      but does not eliminate TPO-induced mitogen-activated protein kinase activation,
      yet it does not alter the synergistic effect of stem cell factor on TPO-induced
      proliferation; and (4) TPO-induced proliferation of early, primary megakaryocyte
      lineage cells does not require Stat-5 phosphorylation. The system reported
      provides an improved approach for Mpl structure-function studies, and the method
      can be applied to any hematopoietic lineage.

PMID- 11238105
TI  - Distinct domains of the human granulocyte-macrophage colony-stimulating factor
      receptor alpha subunit mediate activation of Jak/Stat signaling and
      differentiation.
AB  - The alpha subunit of the human granulocyte-macrophage colony-stimulating factor
      (GM-CSF) receptor has several isoforms that result from alternative splicing
      events. Two forms, alpha-1 and alpha-2, have intracytoplasmic sequences that are
      identical within a membrane-proximal domain but differ completely distally.
      Variant and mutated GM-CSF receptor alpha subunits, along with the beta subunit
      (beta(c) protein) were expressed in M1 murine leukemia cells. and the ability of
      the receptors to signal for differentiation events and to activate Jak/Stat
      signaling pathways was examined. All cell lines expressing both alpha and beta(c)
      proteins exhibited high-affinity binding of radiolabeled human GM-CSF. Receptor
      alpha subunits with intact membrane-proximal intracellular domains could induce
      expression of the macrophage antigen F4/80 and down-regulate the expression of
      CD11b. Addition of recombinant human GM-CSF to cells expressing alpha-1 subunits
      induced the expression of CD86 and tyrosine phosphorylation of Jak-2 and its
      putative substrates SHPTP-2, Stat-5, and the GM-CSF receptor beta(c) subunit.
      Cells containing alpha subunits that lacked a distal domain (term-3) or had the
      alternatively spliced alpha-2 distal domain showed markedly decreased ability to
      support tyrosine phosphorylation of Jak-2 and its substrates or to up-regulate
      CD86. Ligand binding induced stable association of the alpha-1 subunit and
      beta(c) protein. In contrast, the alpha-2 subunit did not stably associate with
      the beta(c) subunit. These data identify potential molecular mechanisms for
      differential signaling of the alpha-1 and alpha-2 proteins. The association of
      unique signaling events with the 2 active GM-CSF alpha subunit isoforms offers a
      model for variable response phenotypes to the same ligand.

PMID- 11238106
TI  - Exogenous clustered neuropilin 1 enhances vasculogenesis and angiogenesis.
AB  - Neuropilin 1 (NP-1) is a receptor for vascular endothelial growth factor (VEGF)
      165 (VEGF165) and acts as a coreceptor that enhances VEGF165 function through
      tyrosine kinase VEGF receptor 2 (VEGFR-2). Transgenic overexpression of np-1
      results in an excess of capillaries and blood vessels and a malformed heart.
      Thus, NP-1 may have a key role in vascular development. However, how NP-1
      regulates vascular development is not well understood. This study demonstrates
      how NP-1 can regulate vasculogenesis and angiogenesis in vitro and in vivo. In
      homozygous np-1 mutant (np-1(-/-)) murine embryos, vascular sprouting was
      impaired in the central nervous system and pericardium. Para-aortic
      splanchnopleural mesoderm (P-Sp) explants from np-1(-/-) mice also had vascular
      defects in vitro. A monomer of soluble NP-1 (NP-1 tagged with Flag epitope)
      inhibited vascular development in cultured wild-type P-Sp explants by
      sequestering VEGF165. In contrast, a dimer of soluble NP-1 (NP-1 fused with the
      Fc part of human IgG) enhanced vascular development in cultured wild-type P-Sp
      explants. Moreover, the NP-1-Fc rescued the defective vascular development in
      cultured np-1(-/-) P-Sp explants. A low dose of VEGF alone did not promote
      phosphorylation of VEGFR-2 on endothelial cells from np-1(-/-) embryos, but
      simultaneous addition of a low dose of VEGF and NP-1-Fc phosphorylated VEGFR-2
      significantly. Moreover, NP-1-Fc rescued the defective vascularity of np-1(-/-)
      embryos in vivo. These results suggest that a dimer form of soluble NP-1 delivers
      VEGF165 to VEGFR-2-positive endothelial cells and promotes angiogenesis.

PMID- 11238107
TI  - Monoclonal antibodies directed to different regions of vascular endothelial
      cadherin extracellular domain affect adhesion and clustering of the protein and
      modulate endothelial permeability.
AB  - Vascular endothelial cadherin (VE-cadherin) is an endothelial cell-specific
      cadherin that plays an important role in the control of vascular organization.
      Blocking VE-cadherin antibodies strongly inhibit angiogenesis, and inactivation
      of VE-cadherin gene causes embryonic lethality due to a lack of correct
      organization and remodeling of the vasculature. Hence, inhibitors of VE-cadherin
      adhesive properties may constitute a tool to prevent tumor neovascularization. In
      this paper, we tested different monoclonal antibodies (mAbs) directed to human VE
      cadherin ectodomain for their functional activity. Three mAbs (Cad 5, BV6, BV9)
      were able to increase paracellular permeability, inhibit VE-cadherin
      reorganization, and block angiogenesis in vitro. These mAbs could also induce
      endothelial cell apoptosis in vitro. Two additional mAbs, TEA 1.31 and Hec 1.2,
      had an intermediate or undetectable activity, respectively, in these assays.
      Epitope mapping studies show that BV6, BV9, TEA 1.31, and Hec 1.2 bound to a
      recombinant fragment spanning the extracellular juxtamembrane domains EC3 through
      EC4. In contrast, Cad 5 bound to the aminoterminal domain EC1. By peptide
      scanning analysis and competition experiments, we defined the sequences TIDLRY
      located on EC3 and KVFRVDAETGDVFAI on EC1 as the binding domain of BV6 and Cad 5,
      respectively. Overall, these results support the concept that VE-cadherin plays a
      relevant role on human endothelial cell properties. Antibodies directed to the
      extracellular domains EC1 but also EC3-EC4 affect VE-cadherin adhesion and
      clustering and alter endothelial cell permeability, apoptosis, and vascular
      structure formation.

PMID- 11238108
TI  - Endothelial cell protein C receptor plays an important role in protein C
      activation in vivo.
AB  - Endothelial cell protein C receptor (EPCR) augments protein C activation by the
      thrombin-thrombomodulin complex about 5-fold in vitro. Augmentation is EPCR
      concentration dependent even when the EPCR concentration is in excess of the
      thrombomodulin. EPCR is expressed preferentially on large blood vessel
      endothelium, raising questions about the importance of protein C-EPCR interaction
      for augmenting systemic protein C activation. In these studies, this question was
      addressed directly by infusing thrombin into baboons in the presence or absence
      of a monoclonal antibody to EPCR that blocks protein C binding. Activated protein
      C levels were then measured directly by capturing the enzyme on a monoclonal
      antibody and assaying with chromogenic substrate. Blocking protein C-EPCR
      interaction resulted in about an 88% decrease in circulating activated protein C
      levels generated in response to thrombin infusion. Leukocyte changes, fibrinogen
      consumption, fibrin degradation products, and vital signs were similar between
      the animals infused with thrombin alone and those infused with thrombin and the
      anti-EPCR antibody. The results indicate that EPCR plays a major role in protein
      C activation and suggest that defects in the EPCR gene might contribute to
      increased risk of thrombosis.

PMID- 11238109
TI  - CD36 associates with CD9 and integrins on human blood platelets.
AB  - The membrane glycoprotein CD36 is involved in platelet aggregation, inhibition of
      angiogenesis, atherosclerosis, and sequestration of malaria-parasitized
      erythrocytes. In this study, immunoprecipitations with anti-CD36 antibodies were
      performed to identify proteins that associate with CD36 in the platelet membrane.
      Platelets were solubilized in 1% Triton X-100, 3-[(3
      cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS), Brij 96, or Brij 99,
      and the proteins that coprecipitated with CD36 were identified by peptide mass
      spectrometry and Western blotting. The tetraspanin protein CD9 and the integrins
      alphaII(b)beta3 and alpha6beta1 specifically coprecipitated with CD36 from
      platelets that were solubilized in CHAPS and Brij 99 but not from platelets that
      were solubilized in Triton X-100. Only CD9 is coprecipitated with CD36 from
      platelets that were solubilized in Brij 96. Reciprocal immunoprecipitations with
      antibodies to CD9, alpha6, alphaIIb, or beta3 from Brij 99-solubilized platelets
      coprecipitated CD36. Coprecipitation of CD36, CD9, and alpha6beta1 was also
      observed on platelets from a patient with Glanzmann thrombasthenia, indicating
      that alphaII(b)beta3 is not required for the other proteins to associate.
      Colocalization of alpha6 and CD36, of CD9 and CD36, and of alpha6 and CD9 was
      observed on intact platelets prior to solubilization, using double
      immunofluorescence microscopy. These data indicate that CD36 associates with CD9
      and integrins on human blood platelets. These associated proteins may mediate or
      participate in some of the diverse biological functions of CD36.

PMID- 11238110
TI  - Serotonin induces the expression of tissue factor and plasminogen activator
      inhibitor-1 in cultured rat aortic endothelial cells.
AB  - Serotonin (5-hydroxytryptamine, or 5-HT), released from activated platelets, not
      only accelerates aggregation of platelets but also is known to promote mitosis,
      migration, and contraction of vascular smooth muscle cells (VSMCs). These effects
      are considered to contribute to thrombus formation and atherosclerosis. The aim
      of this study was to investigate the effects of 5-HT on the expressions of
      coagulative and fibrinolytic factors in rat aortic endothelial cells. Endothelial
      cells were stimulated with various concentrations of 5-HT (0.1 approximately 10
      microM), and the expressions of tissue factor (TF), tissue factor pathway
      inhibitor (TFPI), plasminogen activator inhibitor-1 (PAI-1), and tissue-type
      plasminogen activator (TPA) messenger RNAs (mRNAs) were evaluated by Northern
      blot analysis. The activities of TF and PAI-1 were also measured. TF and PAI-1
      mRNA were increased significantly in a concentration- and time-dependent manner.
      However, TFPI and TPA mRNA expression did not change. The inductions of TF and
      PAI-1 mRNAs were inhibited by a 5-HT1/5-HT2 receptor antagonist (methiothepin)
      and a selective 5-HT2A receptor antagonist (MCI-9042). These results indicate
      that 5-HT increases procoagulant activity and reduces fibrinolytic activities of
      endothelial cells through the 5-HT2A receptor. It was concluded that the
      modulation of procoagulant and hypofibrinolytic activities of endothelial cells
      by 5-HT synergistically promotes thrombus formation at the site of vessel injury
      with the platelet aggregation, VSMC contraction, and VSMC proliferation.

PMID- 11238111
TI  - Urokinase-dependent plasminogen activation is required for efficient skeletal
      muscle regeneration in vivo.
AB  - Plasminogen activators urokinase-type plasminogen activator (uPA) and tissue-type
      plasminogen activator (tPA) are extracellular proteases involved in various
      tissue remodeling processes. A requirement for uPA activity in skeletal
      myogenesis was recently demonstrated in vitro. The role of plasminogen activators
      in skeletal muscle regeneration in vivo in wild-type, uPA-deficient, and tPA
      deficient mice is investigated here. Wild-type and tPA-/- mice completely
      repaired experimentally damaged skeletal muscle. In contrast, uPA-/- mice had a
      severe regeneration defect, with decreased recruitment of blood-derived monocytes
      to the site of injury and with persistent myotube degeneration. In addition, uPA
      deficient mice accumulated fibrin in the degenerating muscle fibers; however, the
      defibrinogenation of uPA-deficient mice resulted in a correction of the muscle
      regeneration defect. A similar severe regeneration deficit with persistent fibrin
      deposition was also reproducible in plasminogen-deficient mice after injury,
      suggesting that fibrinolysis by uPA-mediated plasminogen activation plays a
      fundamental role in skeletal muscle regeneration. In conclusion, the uPA-plasmin
      system is identified as a critical component of the mammalian skeletal muscle
      regeneration process, possibly because it prevents intramuscular fibrin
      accumulation and contributes to the adequate inflammatory response after injury.
      These studies demonstrate the requirement of an extracellular proteolytic cascade
      during muscle regeneration in vivo.

PMID- 11238112
TI  - Tissue factor-mediated endocytosis, recycling, and degradation of factor VIIa by
      a clathrin-independent mechanism not requiring the cytoplasmic domain of tissue
      factor.
AB  - Endocytosis and recycling of coagulation factor VIIa (VIIa) bound to tissue
      factor (TF) was investigated in baby hamster kidney (BHK) cells stably
      transfected with TF or TF derivatives. Cell surface expression of TF on BHK cells
      was required for VIIa internalization and degradation. Approximately 50% of cell
      surface-bound VIIa was internalized in one hour, and a majority of the
      internalized VIIa was degraded soon thereafter. Similar rates of VIIa
      internalization and degradation were obtained with BHK cells transfected with a
      cytoplasmic domain-deleted TF variant or with a substitution of serine for
      cysteine at amino acid residue 245 (C245S). Endocytosis of VIIa bound to TF was
      an active process. Acidification of the cytosol, known to inhibit the
      internalization via clathrin-coated pits, did not affect the internalization of
      VIIa. Furthermore, receptor-associated protein, known to block binding of all
      established ligands to members of the low-density lipoprotein receptor family,
      was without an effect on the internalization of VIIa. Addition of tissue factor
      pathway inhibitor/factor Xa complex did not affect the internalization rate
      significantly. A substantial portion (20% to 25%) of internalized VIIa was
      recycled back to the cell surface as an intact and functional protein. Although
      the recycled VIIa constitutes to only approximately 10% of available cell surface
      TF/VIIa sites, it accounts for 65% of the maximal activation of factor X by the
      cell surface TF/VIIa. In summary, the present data provide evidence that TF
      dependent internalization of VIIa in kidney cells occurs through a clathrin
      independent mechanism and does not require the cytoplasmic domain of TF.

PMID- 11238113
TI  - Allele-dependent transcriptional regulation of the human integrin alpha2 gene.
AB  - Genetically controlled variation in alpha2beta1 expression by human blood
      platelets was previously described. Sixty-two haplotype sequences corresponding
      to the proximal 5' regulatory region (-1096 to +1) of the alpha2 gene were
      compared, and a dimorphic sequence -52C>T was identified that is located
      precisely between 2 tandem Sp1/Sp3 binding elements previously shown to be
      absolutely required for transcriptional activity of this gene in epithelial cell
      lines and the erythroleukemic cell line K562. The gene frequency of -52T in a
      random Caucasian population is approximately 0.35, and the expression of -52T
      correlates directly with reduced densities of platelet alpha2beta1. In mobility
      shift analyses, the -52T substitution attenuates complex formation with both Sp1
      and Sp3. When transfected into the erythroleukemia cell line Dami, promoter
      luciferase constructs bearing the -52T sequence exhibit a 5-fold decrease in
      activity relative to the -52C construct. In transfected CHRF-288-11
      megakaryocytic cells, the corresponding activity decreases by 10-fold. The -52T
      sequence appears to be in linkage disequilibrium with the previously defined
      allele A3 (807C; HPA-5b), known to be associated with diminished expression of
      platelet alpha2beta1. In summary, a natural dimorphism has been identified within
      the proximal 5' regulatory region of the human integrin alpha2 gene that is
      responsible for decreased expression levels of the integrin alpha2beta1 on blood
      platelets through a mechanism that is probably mediated by the nuclear regulatory
      proteins Sp1 and Sp3.

PMID- 11238115
TI  - Human thymus contains 2 distinct dendritic cell populations.
AB  - In this study, 2 distinct populations of mature dendritic cells (DCs) were
      identified in the human thymus. The major population is CD11b-, CD11c+, and
      CD45RO(low) and does not express myeloid-related markers. It displays all the
      characteristics of mature DCs with a typical dendritic morphology, high surface
      levels of HLA-DR, CD40, CD83, and CD86, and expression of DC-lysosome-associated
      membrane glycoprotein messenger RNA (mRNA). In addition, CD11b- thymic DCs do not
      express macrophage inflammatory protein-1alpha (MIP-1alpha) mRNA, but express
      thymus-expressed chemokine (TECK) mRNA and are able to secrete bioactive
      interleukin 12 (IL-12) upon stimulation. In contrast, the minor and variable
      thymic DC population is CD11b+, CD11c(high), and CD45RO(high) and comprises
      CD83+CD14- mature and CD83- CD14+ immature DCs. It expresses macrophage-colony
      stimulating factor receptor, MIP-1alpha mRNA and high amounts of decysin mRNA
      after CD40 activation, but does not express TECK and is a weak bioactive IL-12
      producer. Also identified were the IL-3Ralpha(high) plasmacytoid cells, which are
      present in the thymic cortex and medulla. Upon culture with IL-3,
      granulocyte/macrophage-colony stimulating factor, and CD40 ligand, the
      plasmacytoid cells can adopt a phenotype resembling that of freshly isolated
      CD11b- thymic DCs. However, these plasmacytoid-derived DCs fail to secrete
      bioactive IL-12; therefore, conclusions cannot be made about a direct relation
      between thymic plasmacytoid cells and CD11b- DCs. Whereas CD11b+ thymic DCs
      appear to be related to tonsillar germinal-center DCs, the major CD11b- IL-12
      secreting human thymus DC population has similarities to mouse CD11b- CD8+ DCs.

PMID- 11238114
TI  - Platelet endothelial cell adhesion molecule-1 serves as an inhibitory receptor
      that modulates platelet responses to collagen.
AB  - Platelet responses to collagen are mediated by the combined actions of the
      integrin alpha2beta1, which serves as a major collagen-binding receptor, and the
      GPVI/FcRgamma-chain complex, which transmits collagen-specific activation signals
      into the cell interior through the action of an immunoreceptor tyrosine-based
      activation motif within the cytoplasmic domain of the FcRgamma-chain. Despite
      much progress in identifying components of the signaling pathway responsible for
      collagen-induced platelet activation, virtually nothing is known about the
      regulatory elements that modulate this important hemostatic event. PECAM-1, a
      recently recognized member of the inhibitory receptor family, contains a
      functional immunoreceptor tyrosine-based inhibitory motif within its cytoplasmic
      domain that, when tyrosine phosphorylated, recruits and activates the protein
      tyrosine phosphatase, SHP-2. To test the hypothesis that PECAM-1 functions to
      regulate GPVI/FcRgamma-chain-mediated platelet activation, the responses of wild
      type versus PECAM-1-deficient murine platelets to GPVI-specific agonists were
      compared. Four distinct GPVI/FcRgamma-chain-dependent responses were found to be
      significantly exaggerated in platelets derived from PECAM-1-deficient mice,
      including Mg++-independent adhesion to immobilized fibrillar collagen, collagen
      induced platelet aggregation, platelet aggregation induced by the GPVI-specific
      agonist collagen-related peptide, and GPVI/FcRgamma-chain-induced dense granule
      secretion. Together, these data provide compelling evidence that PECAM-1
      modulates platelet responses to collagen, and they implicate this novel member of
      the inhibitory receptor family in the regulation of primary hemostasis.

PMID- 11238116
TI  - Selective inhibition of interleukin-4 gene expression in human T cells by
      aspirin.
AB  - Previous studies indicated that aspirin (acetylsalicylic acid [ASA]) can have
      profound immunomodulatory effects by regulating cytokine gene expression in
      several types of cells. This study is the first in which concentrations of ASA in
      the therapeutic range were found to significantly reduce interleukin (IL)-4
      secretion and RNA expression in freshly isolated and mitogen-primed human CD4+ T
      cells. In contrast, ASA did not affect IL-13, interferon-gamma, and IL-2
      expression. ASA inhibited IL-4, but not IL-2, promoter-driven chloramphenicol
      acetyltransferase expression in transiently transfected Jurkat T cells. The
      structurally unrelated nonsteroidal anti-inflammatory drugs indomethacin and
      flurbiprofen did not affect cytokine gene expression in T cells, whereas the weak
      cyclo-oxygenase inhibitor salicylic acid was at least as effective as ASA in
      inhibiting IL-4 expression and promoter activity. The inhibitory effect of ASA on
      IL-4 transcription was not mediated by decreased nuclear expression of the known
      salicylate target nuclear factor (NF)-kappaB and was accompanied by reduced
      binding of an inducible factor to an IL-4 promoter region upstream of, but not
      overlapping, the NF of activated T cells- and NF-kappaB-binding P1 element. It is
      concluded that anti-inflammatory salicylates, by means of a previously
      unrecognized mechanism of action, can influence the nature of adaptive immune
      responses by selectively inhibiting the expression of IL-4, a critical effector
      of these responses, in CD4+ T cells.

PMID- 11238117
TI  - Idiotype-specific cytotoxic T lymphocytes in multiple myeloma: evidence for their
      capacity to lyse autologous primary tumor cells.
AB  - Multiple myeloma (MM) is a B-cell malignancy. The monoclonal immunoglobulin,
      secreted by myeloma plasma cells, carries unique antigenic determinants (idiotype
      [Id]) that can be regarded as a tumor-specific antigen. Id-based immunotherapy
      has been explored in myeloma patients for the purpose of enhancing or inducing Id
      specific immune responses that might lead to tumor destruction. However, despite
      some evidence obtained from mouse plasmacytoma models, it is still unclear
      whether Id-specific immunity may play a role in the regulation of tumor cells in
      MM. In the current study, using dendritic cells (DCs) as antigen-presenting
      cells, autologous Id-specific cytotoxic T lymphocyte (CTL) lines containing both
      CD4+ and CD8+ T cells were generated from myeloma patients. The results show that
      Id-specific CTLs not only recognized and lysed autologous Id-pulsed DCs but also
      significantly killed the autologous primary myeloma cells. The cytotoxicity
      against the primary tumor cells was major histocompatibility complex (MHC) class
      I- and, to a lesser extent, class II-restricted, indicating that myeloma cells
      could process Id protein and present Id peptides in the context of their surface
      MHC molecules. Furthermore, the CTLs lysed the target cells mainly through the
      perforin-mediated pathway because Concanamycin A, but not Brefeldin A-the
      selective inhibitors for perforin- or Fas-mediated pathways-abrogated the
      cytolytic activity of the cells. These CTLs secreted predominantly interferon
      gamma and tumor necrosis factor-alpha on antigen stimulation, indicating that
      they belong to the type-1 T-cell subsets. Taken together, these findings
      represent the first demonstration that Id-specific CTLs are able to lyse
      autologous tumor cells in MM and, thus, provide a rationale for Id-based
      immunotherapy in the disease.

PMID- 11238118
TI  - Abnormal intracellular kinetics of cell-cycle-dependent proteins in lymphocytes
      from patients infected with human immunodeficiency virus: a novel biologic link
      between immune activation, accelerated T-cell turnover, and high levels of
      apoptosis.
AB  - Human immunodeficiency virus (HIV)-infection is characterized by loss of CD4+ T
      cells associated with high levels of immune activation, T-cell proliferation, and
      lymphocyte apoptosis. To investigate the role of intrinsic perturbations of cell
      cycle control in the immunopathogenesis of acquired immunodeficiency syndrome
      (AIDS), we studied the expression of cell-cycle-dependent proteins in lymphocytes
      from HIV-infected patients. Cyclin B1 expression, Nucleolar Organizer Regions
      (NORs) number, and NORs area of distribution were all consistently increased in
      HIV-infected patients, but returned to normal after effective antiretroviral
      therapy, suggesting that viral replication is directly implicated in the genesis
      of the observed changes. Analysis of cyclin B1 intracellular turnover showed that
      the increased cyclin B1 expression is (1) caused by defective degradation in the
      presence of normal rates of synthesis, and (2) is temporally associated with
      decreased levels of ubiquitination. After in vitro activation of lymphocytes from
      healthy individuals, cyclin B1 and cdc25 expression and ubiquitination, p34 cdc2
      activity, NORs morphology, and C23/nucleolin localization showed a 72- to 96-hour
      cyclic pattern that led to a biologic state similar to baseline. On the contrary,
      complex but consistent changes of the same indices followed activation of T
      lymphocytes from HIV-infected patients, resulting in a 5-fold increase in
      apoptosis. Overall, our data indicate that a profound dysregulation of cell-cycle
      control is present in lymphocytes from HIV-infected patients. This finding may
      provide a novel biologic link between immune activation, accelerated lymphocyte
      turnover, and increased apoptosis during HIV infection.

PMID- 11238119
TI  - Defective development of NK1.1+ T-cell antigen receptor alphabeta+ cells in zeta
      associated protein 70 null mice with an accumulation of NK1.1+ CD3- NK-like cells
      in the thymus.
AB  - Development of natural killer 1.1+ (NK1.1+) CD3+ (NK1.1+ T) cells was analyzed in
      zeta-associated protein 70 (ZAP-70) null ((-/-)) mice. Both NK1.1+ TCRalphabeta+
      and NK1.1+ TCRgammadelta+ cell populations were absent in the thymus and spleen.
      By contrast, the number of NK1.1+ CD3- cells was increased in these tissues. The
      NK1.1+ CD3- thymocytes in ZAP-70(-/-) mice had surface phenotypes in common with
      NK or NK1.1+ T cells. However, some of them were discordant either with NK cells
      or with NK1.1+ T cells. The NK1.1+ CD3- cells produced interferon-gamma upon
      stimulation with NK1.1 cross-linking in the presence of interleukin-2 and
      exhibited a substantial cytotoxicity against YAC-1 cells. Moreover, the
      generation of NK1.1+ T cells with invariant Valpha14Jalpha281 chains was induced
      from the NK1.1+ CD3- thymocytes following stimulation with phorbol myristate
      acetate and ionomycin in a neonatal thymic organ culture. An introduction of
      TCRalpha and beta transgenes to the ZAP-70(-/-) mice resulted in generation of an
      NK1.1+ TCRalphabeta(dim) population, whereas no substantial CD4+ CD8- or CD4-
      CD8+ population that expressed the introduced TCRalphabeta was generated in the
      mainstream T lineage. These findings demonstrate that ZAP-70 kinase is
      indispensable for the development of NK1.1+ T cells and that the unique NK1.1+
      CD3- thymocytes in ZAP-70(-/-) mice contain immediate precursors of NK1.1+ T
      cells.

PMID- 11238120
TI  - Enhanced immune activity of cytotoxic T-lymphocyte epitope analogs derived from
      positional scanning synthetic combinatorial libraries.
AB  - The pp65(495-503) cytotoxic T-lymphocyte (CTL) epitope from cytomegalovirus (CMV)
      is universally recognized among CMV+ individuals who express an allele of the
      human leukocyte antigen A (HLA-A*0201). The relative binding affinity of the
      epitope to HLA-A*0201 is moderate, and its increased activity might prove
      beneficial in its use as a CTL epitope vaccine. A new approach to enhance the
      activity of T-cell epitopes is the use of positional scanning synthetic
      combinatorial libraries (PS-SCLs). Using a nonamer PS-SCL, the pp65(495-503)
      epitope was modified after screening a CMV-specific T-cell clone (TCC) (3-3F4)
      from which the native peptide sequence was derived. Two peptides with amino acid
      substitutions at P1, P3, P7, and P8 are between 10(3) and 10(4) more active than
      the native epitope. Although the native CTL epitope terminates as a free acid,
      both tetrasubstituted peptides only function as CTL epitopes when the carboxyl
      terminus is amidated. Selective substitution of the native sequence based on PS
      SCL screening results identified 3 amidated monosubstituted and disubstituted
      peptides that are better recognized than the native epitope by TCCs from a cohort
      expressing HLA-A*0201. In vitro stimulation of peripheral blood mononuclear cells
      with each of the peptide epitope analogs stimulated memory CTLs, which recognized
      CMV-infected targets among a high percentage of CMV+ individuals. Binding studies
      of peptide analogs with HLA-Ig (immunoglobulin) dimers and 2 different TCCs
      correlated with in vitro lysis results. These data suggest that increasing the
      activity of CTL epitopes while maintaining broad recognition is possible, which
      holds promise for vaccine development in infectious disease and cancer.

PMID- 11238121
TI  - Down-regulation of CD8+ T-cell expansions in patients with human immunodeficiency
      virus infection receiving highly active combination therapy.
AB  - Analysis of T-cell receptor (TCR) repertoire usage made by peripheral T
      lymphocytes during the chronic phase of HIV-1 infection has revealed the presence
      of clonal expansions of CD8 T cells that are also shown to be largely HIV
      specific. Yet, it remains unclear whether the global repertoire perturbation
      observed during the chronic phase of the infection is also HIV-related and
      reversible in the long term with the application of highly active antiretroviral
      therapy. Furthermore, the diversity and the stability of repertoire usage after a
      relapse of viral replication were never examined. Eight patients were observed
      longitudinally up to 31 months under triple-association therapy. When viral
      replication was steadily suppressed, CD8 repertoires were significantly
      stabilized. Conversely, in situations of incomplete or only transient viral
      suppression, persistence or rebound in repertoire perturbation was observed.
      Finally, a T-cell response remarkably different from baseline, as reflected by a
      repertoire switch, was generated after the discontinuation of highly active
      therapy. In conclusion, a sustained control of HIV replication correlated with
      profound modifications of the CD8 repertoire usage. These data also suggested
      that autovaccination by the withdrawal of antiviral drugs would result in the
      selection and expansion of T-cell clones that were not necessarily dominant
      before the onset of treatment.

PMID- 11238122
TI  - Tissue inhibitor of metalloproteinases 1 regulation of interleukin-10 in B-cell
      differentiation and lymphomagenesis.
AB  - Tissue inhibitors of metalloproteinases (TIMPs), first described as specific
      inhibitors of matrix metalloproteinases, have recently been shown to exert growth
      factor activities. It was previously demonstrated that TIMP-1 inhibits apoptosis
      in germinal center B cells and induces further differentiation. Interleukin-10
      (IL-10) is reported as a vital factor for the differentiation and survival of
      germinal center B cells and is also a negative prognostic factor in non-Hodgkin
      lymphoma (NHL). However, the mechanism of IL-10 activity in B cells and the
      regulation of its expression are not well understood. IL-10 has been shown to up
      regulate TIMP-1 in tissue macrophages, monocytes, and prostate cancer cell lines,
      but IL-10 modulation of TIMP-1 in B cells and the effect of TIMP-1 on IL-10
      expression has not been previously studied. It was found that TIMP-1 expression
      regulates IL-10 levels in B cells and that TIMP-1 mediates specific B-cell
      differentiation steps. TIMP-1 inhibition of apoptosis is not IL-10 dependent.
      TIMP-1 expression in B-cell NHL correlates closely with IL-10 expression and with
      high histologic grade. Thus, TIMP-1 regulates IL-10 expression in B-cell NHL and,
      through the inhibition of apoptosis, appears responsible for the negative
      prognosis associated with IL-10 expression in these tumors.

PMID- 11238123
TI  - UVB-induced apoptosis of human dendritic cells: contribution by caspase-dependent
      and caspase-independent pathways.
AB  - Dendritic cells (DCs) play a central role in the initiation and regulation of the
      immune response. The modalities by which DCs are committed to undergo apoptosis
      are poorly defined. Here it is shown that, unlike death receptor ligands, UVB
      radiation triggers apoptosis of human DCs very efficiently. UVB exposure is
      followed by the activation of caspases 8, 9, and 3, by the loss of mitochondrial
      transmembrane potential (deltaPsim), and by cellular and nuclear fragmentation.
      Caspase inhibitors substantially prevented the occurrence of cellular and nuclear
      fragmentation but had no effect on UVB-induced deltaPsim dissipation.
      Importantly, mature DCs (MDCs) displayed relative resistance to UVB; UVB-induced
      caspase activation and apoptosis were substantially delayed compared to immature
      DCs (IDCs). Resistance correlated with the strong up-regulation of cellular FLIP
      and bcl2 observed in MDCs compared to IDCs.

PMID- 11238124
TI  - B7-H1 costimulation preferentially enhances CD28-independent T-helper cell
      function.
AB  - B7-H1 is a recently described B7-like molecule that costimulates T-cell growth
      and cytokine secretion without binding to CD28, cytotoxic T-lymphocyte antigen-4
      (CTLA-4), and inducible costimulator (ICOS). In this report, a mouse homologue of
      human B7-H1 is identified, and its immunologic functions are studied in vitro and
      in vivo. Mouse B7-H1 shares 69% amino acid homology to the human counterpart.
      Similar to human B7-H1, mouse B7-H1 can be induced to express on macrophages, T
      cells, and B cells and to enhance T-cell proliferation and secretion of
      interleukin-10 (IL-10), interferon-gamma, and granulocyte-macrophage colony
      stimulating factor but not IL-2 and IL-4. Furthermore, B7-H1 preferentially
      costimulates CD4+ T cells independently of CD28 and enhances mixed lymphocyte
      responses to allogeneic antigens. In contrast to B7-1, expression of B7-H1 on
      murine P815 tumor cells by transfection fails to increase allogeneic and
      syngeneic cytolytic T-cell responses in vitro and in vivo. Administration of B7
      H1Ig fusion protein, however, enhances keyhole limpet hemocyanin- specific T-cell
      proliferation and 2,4,6-trinitrophenyl-specific immunoglobulin G2a antibody
      production. The study thus identifies a unique costimulatory pathway that
      preferentially affects T-helper cell functions.

PMID- 11238125
TI  - Interleukin-6 is a growth factor for nonmalignant human plasmablasts.
AB  - Interleukin-6 (IL-6), although often regarded as a B-cell differentiation factor,
      was recently described as the essential survival factor for human plasmablasts in
      vivo in reactive plasmacytosis. The present study reinvestigated the roles of IL
      6 and IL-2 in the generation of plasma cells from human memory B cells in vitro.
      The cells involved in this differentiation process were identified as
      preplasmablasts (CD20+/-CD38+/-CD138-), plasmablasts (CD20-CD38++CD138-), and
      early plasma cells (CD20-CD38+++CD138+++). IL-2 or IL-10 induced a strong
      generation of plasmablasts and early plasma cells (PCs). Compared to IL-2 or IL
      10, IL-6 alone was inefficient at PC generation. However, when combined with IL-2
      or IL-10, IL-6 enhanced generation of early PCs. Moreover, anti-IL-6 monoclonal
      antibody markedly reduced IL-2-induced generation of early plasma cells, but not
      of plasmablasts. These roles of IL-2 and IL-6 were consistent with the difference
      in the expression of their respective receptors (R). CD25 (IL-2Ralpha) was
      increased 72 +/- 10-fold on activated B cells, but decreased and then disappeared
      on plasmablasts. Conversely, CD126 (IL-6Ralpha) was barely expressed on activated
      B cells, but increased 18 +/- 2-fold on preplasmablasts. Finally, IL-6 enhanced
      the proliferation (2-fold increase) of IL-2-generated plasmablasts. In
      conclusion, the data indicate that IL-6 is a growth factor for nonmalignant human
      plasmablasts.

PMID- 11238126
TI  - Cell-cycle-dependent activation of mitogen-activated protein kinase kinase (MEK
      1/2) in myeloid leukemia cell lines and induction of growth inhibition and
      apoptosis by inhibitors of RAS signaling.
AB  - Disruption of the RAS-to-mitogen-activated protein kinase (MAPK/ERK) signaling
      pathway, either directly through activating RAS gene mutations or indirectly
      through other genetic aberrations, plays an important role in the molecular
      pathogenesis of myeloid leukemias. Constitutive activation of ERK-1/2 and MEK
      1/2, which elicit oncogenic transformation in fibroblasts, has recently been
      observed in acute myeloid leukemias (AML). In this study, the activation of the
      RAS-to-MAPK cascade in 14 AML and 5 chronic myeloid leukemia (CML) cell lines is
      examined and correlated with the effects of a panel of 9 RAS signaling inhibitors
      on cell viability, colony formation, cell-cycle progression, and induction of
      apoptosis. Activation of MEK, ERK, and the transcription factors CREB-1, ATF-1,
      and c-Myc is demonstrated in the majority of the cell lines (9 of 14 AML and 2 of
      5 CML cell lines). Although activation of the ERK cascade did not always
      correlate with the presence of activating RAS mutations or BCR-Abl, it is linked
      to the G0/G1 and the G2/M phase of the cell cycle. In contrast to most inhibitors
      (eg, B581, Cys-4-Abs-Met, FPT-2, FTI-276, and FTS), a significant growth
      inhibition was only observed for FTI-277 (19 of 19), FPT-3 (10 of 19), and the
      MEK inhibitors U0126 (19 of 19) and PD098059 (8 of 19). Treatment of NB-4 cells
      with FTI-277 primarily resulted in a G2/M block, whereas treatment with FPT-3 and
      U0126 led to induction of apoptosis. FTI-277 revealed strong toxicity toward
      normal purified CD34+ cells. The results suggest differences in the mechanisms of
      action and support a potential therapeutic usefulness of these inhibitors in the
      treatment of myeloid leukemias.

PMID- 11238127
TI  - Involvement of caspase-2 long isoform in Fas-mediated cell death of human
      leukemic cells.
AB  - Engagement of the plasma membrane receptor Fas can induce apoptosis of leukemic
      cells. Signaling through Fas requires the formation of a death-inducing signaling
      complex (DISC) that involves the cytoplasmic domain of Fas, the adaptor molecule
      FADD/MORT-1, and procaspase-8. The present study investigated whether another
      caspase, known as procaspase-2L, played a role in Fas-mediated cell death. A
      series of human leukemic variant cells was derived by stable transfection with a
      CASP2L antisense construct (CASP2L/AS). Specific down-regulation of procaspase-2L
      decreased the sensitivity of these cells to apoptosis induced by an agonistic
      anti-Fas antibody (Ab, clone CH11), as determined by studying DNA fragmentation,
      chromatin condensation, and externalization of phosphatidylserine on the plasma
      membrane. In leukemic cells transfected with an empty vector, anti-Fas Ab
      treatment activated caspase-8, decreased the expression of the BH3 domain-only
      protein Bid, triggered the release of cytochrome c from the mitochondria to the
      cytosol, and activated caspase-3. All these events could not be observed when
      CASP2L/AS cells were similarly treated with anti-Fas Abs. CASP2L/AS transfection
      did not inhibit the formation of the DISC and no direct interaction between
      procaspase-2L and either Fas or FADD or procaspase-8 was identified. Down
      regulation of procaspase-2L inhibited anti-Fas Ab-mediated cleavage of c-FLIP
      (FLICE-inhibitory protein), a protein that interferes with the formation of a
      functional DISC. These results suggest that the long isoform of caspase-2 plays a
      role in the Fas-mediated pathway to cell death by contributing to caspase-8
      activation at the DISC level.

PMID- 11238128
TI  - Lymphocyte predominance Hodgkin disease is characterized by recurrent genomic
      imbalances.
AB  - Single-cell polymerase chain reaction (PCR) has been used as a tool to
      demonstrate clonality and B-cell origin of Reed-Sternberg (RS) cells in Hodgkin
      disease (HD). An analogous approach was used to investigate genomic imbalances in
      a (cyto)genetically poorly characterized subentity: lymphocyte predominance
      Hodgkin disease (LPHD). Nineteen cases of LPHD were selected for a comparative
      genomic hybridization (CGH) study. CGH was performed with degenerate
      oligonucleotide primed-PCR (DOP-PCR)-amplified DNA from 4-5 microdissected CD20+
      malignant cells. All analyzed cases revealed a high number of genomic imbalances
      (average 10.8 per case), involving all chromosomes but the excluded 19, 22, and
      Y, indicating a high complexity of LPHD. The majority of detected aberrations
      were recurrent. Gain of 1, 2q, 3, 4q, 5q, 6, 8q, 11q, 12q, and X, and loss of
      chromosome 17 were identified in 36.8% to 68.4% of the analyzed cases. Some of
      them have also been found in non-Hodgkin lymphoma (NHL), and possibly represent
      secondary changes associated with disease progression. Gain of 2q, 4q, 5q, 6,
      11q, however, are much more rarely observed in NHL and could be more specifically
      associated with LPHD. Particularly interesting is a frequent overrepresentation
      of chromosome arm 6q, a region usually deleted in NHL. Rearrangement of the BCL6
      gene (3q27) demonstrated by cytogenetics and fluorescence in situ hybridization
      in 2 cases in this study suggests its contribution in pathogenesis of LPHD. In
      conclusion, the data show a consistent occurrence of genomic alterations in LPHD
      and highlight genomic regions that might be relevant for development and/or
      progression of this lymphoma entity.

PMID- 11238129
TI  - Platelet-endothelial cell adhesion molecule-1 (PECAM-1)-deficient mice
      demonstrate a transient and cytokine-specific role for PECAM-1 in leukocyte
      migration through the perivascular basement membrane.
AB  - Studies with neutralizing antibodies have indicated roles for platelet
      endothelial cell adhesion molecule-1 (PECAM-1) in leukocyte migration through the
      endothelium and the perivascular basement membrane. Because some of these
      findings have been contentious, this study aimed to explore the role of PECAM-1
      in leukocyte migration by analyzing leukocyte responses in interleukin 1beta (IL
      1beta)- and tumor necrosis factor-alpha (TNFalpha)-activated cremasteric venules
      of PECAM-1-deficient mice using intravital and electron microscopy. Although no
      differences in levels of leukocyte rolling flux or firm adhesion were observed, a
      delay in leukocyte transmigration in response to IL-1beta, but not TNFalpha, was
      detected in PECAM-1-deficient mice. Electron microscopy indicated that this delay
      occurred at the level of perivascular basement membrane. To address the cytokine
      specificity of PECAM-1 dependence, in vitro experiments demonstrated that
      TNFalpha, but not IL-1beta, could induce rapid adhesion of murine neutrophils to
      protein-coated surfaces, suggesting that TNFalpha elicited leukocyte
      transmigration in wild-type mice via direct stimulation of leukocytes. In
      summary, the results suggest a regulatory role for PECAM-1 in leukocyte migration
      through the perivascular basement membrane, a role that appears to be cytokine
      specific and associated with the ability of the cytokine to stimulate rapid
      neutrophil adhesion.

PMID- 11238130
TI  - Erythroid Kruppel-like factor (EKLF) coordinates erythroid cell proliferation and
      hemoglobinization in cell lines derived from EKLF null mice.
AB  - Erythroid Kruppel-like factor (EKLF) is a transcription factor of the C2H2 zinc
      finger class that is essential for definitive erythropoiesis. We generated
      immortal erythroid cell lines from EKLF(-/-) fetal liver progenitor cells that
      harbor a single copy of the entire human beta-globin locus and then reintroduced
      EKLF as a tamoxifen-inducible, EKLF-mutant estrogen receptor (EKLF-ER) fusion
      protein. Addition of tamoxifen resulted in enhanced differentiation and
      hemoglobinization, coupled with reduced proliferation. Human beta-globin gene
      expression increased significantly, whereas gamma-globin transcripts remained
      elevated at levels close to endogenous mouse alpha-globin transcript levels. We
      conclude that EKLF plays a role in regulation of the cell cycle and
      hemoglobinization in addition to its role in beta-globin gene expression. The
      cell lines we used will facilitate structural and functional analyses of EKLF in
      these processes and provide useful tools for the elucidation of nonglobin EKLF
      target genes.

PMID- 11238131
TI  - Membrane instability in late-stage erythropoiesis.
AB  - During maturation of the red blood cell (RBC) from the nucleated normoblast stage
      to the mature biconcave discocyte, both the structure and mechanical properties
      of the cell undergo radical changes. The development of the mechanical stability
      of the membrane reflects underlying changes in the organization of membrane
      associated cytoskeletal proteins, and so provides an assessment of the time
      course of the development of membrane structural organization. Membrane stability
      in maturing erythrocytes was assessed by measuring forces required to form thin,
      tubular, lipid strands (tethers) from the surfaces of mononuclear cells obtained
      from fresh human marrow samples, marrow reticulocytes, circulating reticulocytes,
      and mature erythrocytes. Cells were biotinylated and manipulated with a
      micropipette to form an adhesive contact with a glass microcantilever, which gave
      a measure of the tethering force. The cell was withdrawn at controlled velocity
      and aspiration pressure to form a tether from the cell surface. The mean force
      required to form tethers from marrow reticulocytes and normoblasts was 27 +/- 9
      pN, compared to 54 +/- 14 pN for mature cells. The energy of dissociation of the
      bilayer from the underlying skeleton increases 4-fold between the marrow
      reticulocyte stage and the mature cell, demonstrating that the mechanical
      stability of the membrane is not completely established until the very last
      stages of RBC maturation.

PMID- 11238132
TI  - Replicative stress after allogeneic bone marrow transplantation: changes in
      cycling of CD34+CD90+ and CD34+CD90- hematopoietic progenitors.
AB  - To further characterize hematopoietic "replicative stress" induced by bone marrow
      transplantation (BMT), the cell-cycle status of CD90+/- subsets of marrow CD34+
      cells obtained 2 to 6 months after transplantation from 11 fully chimeric
      recipients was examined. Cycling profiles, derived by flow cytometry after
      staining with Hoechst 33342 and pyronin Y, were compared with those of 14 healthy
      marrow donors. Primitive CD34+CD90+ cells represented a smaller proportion of
      CD34+ cells in recipients (10% +/- 4% versus 19.6% +/- 5.3% in donors; P <.0001)
      and were more mitotically active, with the proportion of cells in S/G2/M nearly 4
      fold higher than in donors (15.6% +/- 3% and 4.4% +/- 1.6%, respectively; P
      <.0001). By comparison, there was a modest increase in the proportion of
      CD34+CD90- progenitors in S/G2/M after BMT (10.9% +/- 1% vs 9.6% +/- 2% in
      donors; P =.04). Replicative stress after BMT is borne predominantly by cells in
      a diminished CD34+CD90+ population.

PMID- 11238133
TI  - Activation of multiple cryptic donor splice sites by the common congenital
      afibrinogenemia mutation, FGA IVS4 + 1 G-->T.
AB  - Our recent studies on the molecular basis of the autosomal recessive disorder
      congenital afibrinogenemia showed that the most common mutation is a donor splice
      mutation in FGA intron 4, IVS4 + 1 G-->T, accounting for approximately half of
      disease alleles. The effect of this mutation on messenger RNA (mRNA) splicing,
      however, remained unproven. COS-7 cells transfected with a normal plasmid
      construct produced 100% mRNA molecules with correct splicing, whereas cells
      transfected with a mutant construct produced multiple aberrant mRNAs, due to
      utilization of cryptic donor splice sites situated in exon 4 and intron 4. One
      particular site situated 4 base pairs (bp) downstream of the normal site was used
      in 85% of transcripts causing afibrinogenemia by a 4-bp insertion-frameshift,
      leading to premature alpha-chain truncation. Our results confirm the utility of
      transfecting COS-7 cells to study mRNA splice-site mutations and demonstrate that
      the common FGA IVS4 variant is a null mutation leading to afibrinogenemia.

PMID- 11238134
TI  - Time course of increasing numbers of mutations in the granulocyte colony
      stimulating factor receptor gene in a patient with congenital neutropenia who
      developed leukemia.
AB  - Point mutations in the granulocyte colony-stimulating factor receptor (G-CSFR)
      gene have been linked to the development of secondary leukemia in patients with
      congenital neutropenia (CN). This report presents data on a now 18-year-old
      patient with CN who has received G-CSF treatment since 1989 and who developed
      acute myeloid leukemia (AML) in 1998. To evaluate whether there is an association
      between the occurrence of point mutations of the G-CSFR gene and development of
      secondary AML, DNA/messenger RNA of neutrophils and mononuclear cells from this
      patient were analyzed at different time points by polymerase chain reaction and
      subsequent cloning by DNA sequencing of representative numbers of individual
      clones. Findings suggest an increasing instability of the G-CSFR gene in time as
      judged by increasing numbers of mutations proposed to be one important step in
      the development of AML in this patient.

PMID- 11238135
TI  - Acquired factor X deficiency in patients with amyloid light-chain amyloidosis:
      incidence, bleeding manifestations, and response to high-dose chemotherapy.
AB  - Acquired deficiency of factor X occurs in patients with systemic amyloid light
      chain (AL) amyloidosis, presumably due to adsorption of factor X to amyloid
      fibrils. Of 368 consecutive patients with systemic AL amyloidosis evaluated at
      Boston Medical Center, 32 patients (8.7%) had factor X levels below 50% of
      normal. Eighteen of these patients (56%) had bleeding complications, which were
      more frequent and severe in the 12 patients below 25% of normal; 2 episodes were
      fatal. Ten factor X-deficient patients received high-dose melphalan chemotherapy
      followed by autologous stem cell transplantation. Of 7 patients alive 1 year
      after treatment, 4 had a complete hematologic response, and all 4 experienced
      improvement in their factor X levels. One of 2 additional patients with partial
      hematologic responses had improvement in factor X. Thus, aggressive treatment of
      the underlying plasma cell dyscrasia in AL amyloidosis can lead to the
      amelioration of amyloid-related factor X deficiency.

PMID- 11238136
TI  - The effect of multidrug-resistance 1 gene versus neo transduction on ex vivo and
      in vivo expansion of rhesus macaque hematopoietic repopulating cells.
AB  - Transduction of murine stem cells with a multidrug-resistance 1 gene (MDR1)
      retrovirus results in dramatic ex vivo and in vivo expansion of repopulating
      cells accompanied by a myeloproliferative disorder. Given the use of MDR1
      containing vectors in human trials, investigations have been extended to nonhuman
      primates. Peripheral blood stem cells from 2 rhesus monkeys were collected, CD34
      enriched, split into 2 portions, and transduced with either MDR1 vectors or neo
      vectors and continued in culture for a total of 10 days before reinfusion. At
      engraftment, the copy number in granulocytes was extremely high from both MDR
      vectors and neo vectors, but the copy number fell to 0.01 to 0.05 for both. There
      were no perturbations of the leukocyte count or differential noted. After 3
      cycles of stem cell factor/granulocyte colony-stimulating factor, there were no
      changes in the levels of MDR1 vector- or neo vector-containing cells. There was
      no evidence for expansion of MDR1 vector-transduced cells. Long-term engraftment
      with MDR1 vector- and neo vector-transduced cells occurred despite prolonged
      culture.

PMID- 11238137
TI  - Foot and mouth disease: the human consequences. The health consequences are
      slight, the economic ones huge.

PMID- 11238138
TI  - HIV and infertility: time to treat. There's no justification for denying
      treatment to parents who are HIV positive.

PMID- 11238139
TI  - Practice based primary care research networks. They work and are ready for full
      development and support.

PMID- 11238140
TI  - Management of stage 1 endometrial carcinoma. Postoperative radiotherapy is not
      justified in women with medium risk disease.

PMID- 11238141
TI  - Societal responsibilities of clinical trial sponsors. Lack of commercial pay off
      is not a legitimate reason for stopping a trial.

PMID- 11238142
TI  - Wyeth suppresses research on pill, programme claims.

PMID- 11238148
TI  - WHO says tobacco industry "used" institute to undermine its policies.

PMID- 11238147
TI  - Surfactant trial in Latin American infants criticised.

PMID- 11238149
TI  - India invests heavily in genomics research.

PMID- 11238150
TI  - Comparison of elderly people's technique in using two dry powder inhalers to
      deliver zanamivir: randomised controlled trial.
AB  - OBJECTIVE: To determine whether elderly people can learn to use the inhaler used
      to deliver zanamivir (Relenza Diskhaler) as effectively as the Turbohaler and to
      identify which aspects of inhaler technique are most problematic. DESIGN:
      Randomised, controlled, intervention study. SETTING: Wards for acute elderly care
      in a large district general hospital. PARTICIPANTS: 73 patients who were
      unfamiliar with the use of an inhaler, aged 71 to 99 (mean 83) years. MAIN
      OUTCOME MEASURES: Initial scores and changes in scores 24 hours later using a 10
      point scoring system of five aspects of inhaler technique. RESULTS: 38 patients
      were allocated the Relenza Diskhaler and 35 the Turbohaler. The mean total score
      was significantly greater in the Turbohaler than Diskhaler groups both initially
      (8.74 v 7.05) and after 24 hours (8.28 v 5.43). The major difference between
      inhalers was in loading and priming. After tuition 50% (19 of 38) of patients
      allocated the Diskhaler were unable to load and prime the device and 65% (24 of
      37) were unable to do so 24 hours later. Of those allocated the Turbohaler, two
      patients were unable to load and prime the device after initial review and one
      after 24 hours. CONCLUSION: Most elderly people cannot use the inhaler device
      used to deliver the anti-influenza drug zanamivir. Treatment with this drug is
      unlikely to be effective in elderly people unless the delivery system is
      improved.

PMID- 11238152
TI  - Effect of peer led programme for asthma education in adolescents: cluster
      randomised controlled trial.
AB  - OBJECTIVE: To determine the effect of a peer led programme for asthma education
      on quality of life and related morbidity in adolescents with asthma. DESIGN:
      Cluster randomised controlled trial. SETTING: Six high schools in rural
      Australia. PARTICIPANTS: 272 students with recent wheeze, recruited from a cohort
      of 1515 students from two school years (mean age 12.5 and 15.5 years); 251
      (92.3%) completed the study. INTERVENTION: A structured education programme for
      peers comprising three steps (the "Triple A Program"). MAIN OUTCOME MEASURES:
      Quality of life, school absenteeism, asthma attacks, and lung function. RESULTS:
      When adjusted for year and sex, mean total quality of life scores showed
      significant improvement in the intervention than control group. Clinically
      important improvement in quality of life (>0.5 units) occurred in 25% of students
      with asthma in the intervention group compared with 12% in the control group
      (P=0.01). The number needed to treat was 8 (95% confidence interval 4.5 to 35.7).
      The effect of the intervention was greatest in students in year 10 and in
      females. Significant improvements occurred in the activities domain (41% v 28%)
      and in the emotions domain (39% v 19%) in males in the intervention group. School
      absenteeism significantly decreased in the intervention group only. Asthma
      attacks at school increased in the control group only. CONCLUSION: The triple A
      programme leads to a clinically relevant improvement in quality of life and
      related morbidity in students with asthma. Wider dissemination of this programme
      in schools could play an important part in reducing the burden of asthma in
      adolescents.

PMID- 11238153
TI  - Lifestyle, hormones, and risk of breast cancer.

PMID- 11238151
TI  - Comparison of effects of amphotericin B deoxycholate infused over 4 or 24 hours:
      randomised controlled trial.
AB  - OBJECTIVE: To test the hypothesis that amphotericin B deoxycholate is less toxic
      when given by continuous infusion than by conventional rapid infusion. DESIGN:
      Randomised, controlled, non-blinded, single centre study. SETTING: University
      hospital providing tertiary clinical care. PATIENTS: 80 mostly neutropenic
      patients with refractory fever and suspected or proved invasive fungal
      infections. INTERVENTION: Patients were randomised to receive 0.97 mg/kg
      amphotericin B by continuous infusion over 24 hours or 0.95 mg/kg by rapid
      infusion over four hours. MAIN OUTCOME MEASURES: Patients were evaluated for side
      effects related to infusion, nephrotoxicity, and mortality up to three months
      after treatment. Analysis was on an intention to treat basis. RESULTS: Patients
      in the continuous infusion group had fewer side effects and significantly reduced
      nephrotoxicity than those in the rapid infusion group. Overall mortality was
      higher during treatment and after three months' follow up in the rapid infusion
      than in the continuous infusion group. CONCLUSION: Continuous infusions of
      amphotericin B reduce nephrotoxicity and side effects related to infusion without
      increasing mortality.

PMID- 11238154
TI  - Light eye colour linked to deafness after meningitis.

PMID- 11238155
TI  - Networks for research in primary health care.

PMID- 11238156
TI  - Recent advances: International perspectives on health inequalities and policy.

PMID- 11238157
TI  - Raised cortisol excretion rate in urine and contamination by topical steroids.

PMID- 11238158
TI  - ABC of diseases of liver, pancreas, and biliary system. Acute pancreatitis.

PMID- 11238160
TI  - Is bigger better for primary care groups and trusts?

PMID- 11238162
TI  - Premature discontinuation of clinical trial for reasons not related to efficacy,
      safety, or feasibility.

PMID- 11238163
TI  - Asylum seekers and refugees in Britain. The health of survivors of torture and
      organised violence.

PMID- 11238171
TI  - Why have sex?

PMID- 11238174
TI  - Patterns of p53 G-->T transversions in lung cancers reflect the primary mutagenic
      signature of DNA-damage by tobacco smoke.
AB  - It is unquestionable that the major cause of lung cancer is cigarette smoking.
      p53 mutations are common in lung cancers from smokers but less common in non
      smokers. A large fraction of the p53 mutations in lung cancers are G-->T
      transversions, a type of mutation that is infrequent in other tumors aside from
      hepatocellular carcinoma. Previous studies have indicated that there is a good
      correlation between G-->T transversion hotspots in lung cancers and sites of
      preferential formation of polycyclic aromatic hydrocarbon (PAH) adducts along the
      p53 gene. The origin of p53 mutations in lung cancer has been questioned by
      recent reports suggesting that there are no significant differences in p53
      mutation spectra between smokers and non-smokers and between lung cancers and non
      lung cancers [S.N. Rodin and A.S. Rodin (2000) Human lung cancer and p53: The
      interplay between mutagenesis and selection. P:roc. Natl Acad. Sci. USA, 97,
      12244-12249]. We have re-assessed these issues by using the latest update of the
      p53 mutation database of the International Agency for Research on Cancer (14 051
      entries) as well as recent data from the primary literature on non-smokers. We
      come to the conclusion that the p53 mutation spectra are different between
      smokers and non-smokers and that this difference is highly statistically
      significant (G-->T transversions are 30 versus 10%; P < 0.0001, chi2 test). A
      similar difference is seen between lung cancers and non-lung cancers. At a number
      of mutational hotspots common to all cancers, a large fraction of the mutations
      are G-->T transversions in lung cancers but are almost exclusively G-->A
      transitions in non-lung cancers. Our data reinforce the notion that p53 mutations
      in lung cancers can be attributed to direct DNA damage from cigarette smoke
      carcinogens rather than to selection of pre-existing endogenous mutations.

PMID- 11238175
TI  - Modulation of apoptosis by cigarette smoke and cancer chemopreventive agents in
      the respiratory tract of rats.
AB  - Preclinical studies may elucidate the meaning of biomarkers applicable to
      epidemiologic studies and to clinical trials for cancer prevention. No study has
      explored so far the effect of cigarette smoke on apoptosis in vivo. We evaluated
      modulation of apoptosis in cells of the respiratory tract of smoke-exposed
      Sprague-Dawley rats both by morphological analysis and TUNEL method. In a first
      study, exposure of rats to mainstream cigarette smoke for either 18 or 100
      consecutive days produced a significant and time-dependent increase in the
      proportion of apoptotic cells in the bronchial and bronchiolar epithelium. Oral
      N:-acetylcysteine did not affect the background frequency of apoptosis but
      significantly and sharply decreased smoke-induced apoptosis. In a second study,
      exposure of rats to a mixture of sidestream and mainstream smoke for 28
      consecutive days resulted in a >10-fold increase in the frequency of pulmonary
      alveolar macrophages undergoing apoptosis. Dietary administration of either 5,6
      benzoflavone, 1,2-dithiole-3-thione or oltipraz did not affect the frequency of
      smoke-induced apoptosis, whereas phenethyl isothiocyanate produced a further
      significant enhancement. Again, N-acetylcysteine and its combination with
      oltipraz significantly decreased smoke-induced apoptosis. In both studies
      exposure to smoke resulted in a sharp increase of cells positive for
      proliferating cell nuclear antigen (PCNA), which was unaffected by the examined
      chemopreventive agents. These findings highlight the concept that modulation of
      apoptosis has diversified meanings. Different meanings (as explained in the
      following lines). First, the apoptotic process is triggered as a defense system
      against genotoxic agents, such as the components of cigarette smoke. The further
      induction produced by phenethyl isothiocyanate, favoring removal of damaged
      cells, represents an example of a detoxification mechanism. Inhibition of smoke
      induced apoptosis by N:-acetylcysteine should be interpreted as an epiphenomenon
      of antigenotoxic mechanisms, as shown in parallel studies evaluating modulation
      of DNA alterations in the respiratory tract of the same animals. Thus, it is
      important to discriminate between whether the opposite modulation of apoptosis is
      per se a protective mechanism or the beneficial outcome of other mechanisms
      inhibiting genotoxicity.

PMID- 11238176
TI  - Tumor necrosis factor alpha is not required for WY14,643-induced cell
      proliferation.
AB  - It has been proposed that the cytokine tumor necrosis factor alpha (TNFalpha)
      stimulates peroxisome proliferator-induced hepatic cell proliferation. To test
      this hypothesis, induction of peroxisome proliferation and hepatocyte
      proliferation were compared in wild-type C57Bl/6 and TNFalpha knockout mice.
      Animals were dosed with either vehicle or 100 mg/kg/day WY14,643 by oral gavage
      for 4 days. Liver to brain weight ratios increased in both wild-type and TNFalpha
      knockout animals after WY14,643 administration. In addition, WY14,643-treated
      wild-type C57Bl/6 and TNFalpha knockout mice displayed marked hepatic induction
      of fatty acyl-CoA oxidase activity (approximately 8-fold) and mRNA content
      (approximately 5-fold). Electron microscopic examination confirmed increased
      numbers of peroxisomes in hepatocytes in both mouse models. Moreover, WY14,643
      markedly induced hepatic cell proliferation (approximately 15-fold) in both wild
      type C57Bl/6 and TNFalpha knockout mice as measured by bromodeoxyuridine
      incorporation into hepatocyte nuclei. In addition, a 50% decrease in TNFalpha
      mRNA was observed in wild-type mice after treatment with WY14,643. These results
      suggest that the hepatocellular proliferation induced after peroxisome
      proliferator treatment occurs independently of TNFalpha signaling.

PMID- 11238177
TI  - Rates of base excision repair are not solely dependent on levels of initiating
      enzymes.
AB  - The oxidized base 8-oxo-7,8-dihydroguanine (8-oxoG), the product of deamination
      of cytosine uracil (U), and the sites of base loss [abasic (AP) sites] are among
      the most frequent mutagenic lesions formed in the human genome under
      physiological conditions. In human cells, the enzymatic activities initiating DNA
      base excision repair (BER) of 8-oxoG, U and AP sites are the 8-oxoG DNA
      glycosylase (hOGG1), the U-DNA glycosylase (UNG) and the major hydrolytic AP
      endonuclease (APE/HAP1), respectively. In recent work, we observed that BER of
      the three lesions occurs in human cell extracts with different efficacy. In
      particular, 8-oxoG is repaired on average 4-fold less efficiently than U, which,
      in turn, is repaired 7-fold slower than the natural AP site. To discriminate
      whether the different rates of repair may be linked to different expression of
      the initiating enzymes, we have determined the amount of hOGG1, UNG and APE/HAP1
      in normal human cell extracts by immunodetection techniques. Our results show
      that a single human fibroblast contains 123 000 +/- 22 000 hOGG1 molecules, 178
      000 +/- 20 000 UNG molecules and 297 000 +/- 50 000 APE/HAP1 molecules. These
      limited differences in enzyme expression levels cannot readily explain the
      different rates at which the three lesions are repaired in vitro. Addition to
      reaction mixtures of titrated amounts of purified hOGG1, UNG and APE/HAP1
      variably stimulated the in vitro repair replication of 8-oxoG, U and the AP site
      respectively and the increase was not always proportional to the amount of added
      enzyme. We conclude that the rates of BER depend only in part on cellular levels
      of initiating enzymes.

PMID- 11238178
TI  - A multi-biomarker approach to study the effects of smoking on oxidative DNA
      damage and repair and antioxidative defense mechanisms.
AB  - We investigated the effects of smoking-induced oxidative stress in healthy
      volunteers (21 smokers versus 24 non-smokers) by quantifying various markers of
      oxidative DNA damage and repair, and antioxidative defense mechanisms.
      Lymphocytic 7-hydroxy-8-oxo-2'-deoxyguanosine (8-oxo-dG) levels measured by high
      performance liquid chromatography with electrochemical detection, were
      significantly lower in smokers as compared with non-smokers (38.6 +/- 5.2 versus
      50.9 +/- 4.6/10(6) dG, P = 0.05). The levels of oxidized pyrimidine bases in
      lymphocytes of smokers quantified by the endonuclease III-modified comet assay
      were non-significantly lower than those of non-smokers (% DNA in tail: 13 +/- 3
      versus 14 +/- 2; tail length: 69 +/- 13 versus 96 +/- 10; tail moment: 6416 +/-
      1220 versus 7545 +/- 1234). Urinary excretion levels of 8-hydroxy-2'
      deoxyguanosine (8-OH-dG) assessed by enzyme-linked immunosorbent assay did not
      differ significantly between smokers and non-smokers (197 +/- 31 versus 240 +/-
      33 ng/body mass index, P = 0.3). Overall DNA repair activity expressed as
      unscheduled DNA synthesis in blood leukocytes, was not significantly different
      between smokers and non-smokers (2.9 +/- 0.3 versus 3.3 +/- 0.3, P = 0.4). Plasma
      antioxidative capacity measured by the Trolox equivalent antioxidant capacity
      assay was slightly higher in smokers as compared with non-smokers (440 +/- 16
      versus 400 +/- 15 microM Trolox equivalent, P = 0.09), and it was significantly
      related to lymphocytic 8-oxo-dG levels (r = 0.4, P = 0.001). Genotyping of human
      8-OH-dG glycosylase/apurinic lyase and glutathione S-transferase M1 showed that a
      polymorphism in either or both of the two genes does not affect any of the
      quantified biomarkers. We conclude that oxidative stress imposed by cigarette
      smoking has a low impact upon certain pathways involved in DNA damage and the
      antioxidative defense system.

PMID- 11238179
TI  - Nucleotide excision repair gene XPD polymorphisms and genetic predisposition to
      melanoma.
AB  - The nucleotide excision repair pathway has evolved to deal with UV light-induced
      DNA damage. Individuals with the rare inherited nucleotide excision repair
      deficiency disease xeroderma pigmentosum have a 1000-fold increased incidence of
      skin cancer. We are interested in the possibility that more subtle changes in
      nucleotide excision repair genes, resulting in either a reduced capacity for
      repair or in altered interactions between repair proteins and components of the
      cell cycle control machinery, might constitute important genetic risk factors for
      the development of skin cancer in the general population. To investigate this
      hypothesis we have compared the frequency of polymorphisms in exons 6, 22 and 23
      of the XPD gene in melanoma patients and a control group. For each of these two
      allele polymorphisms one of the alleles was over-represented in the melanoma
      group and there was a significant association with melanoma. Importantly, this
      association did not extend to markers immediately flanking the XPD gene, thus
      providing evidence that XPD gene polymorphisms might predispose to melanoma in
      the general population. There is a report that one of the polymorphic XPD alleles
      (exon 23 Lys), which is over-represented in the melanoma group, has reduced
      repair proficiency and we discuss the possibility that this is the causal change
      to the XPD gene that predisposes to melanoma.

PMID- 11238180
TI  - Quercetin inhibits the expression and function of the androgen receptor in LNCaP
      prostate cancer cells.
AB  - The androgen receptor (AR) is involved in the development and progression of
      prostate cancer. In order to find new compounds that may present novel mechanisms
      to attenuate the function of AR, we investigated the effect of a natural
      flavonoid chemical, quercetin, on androgen action in an androgen-responsive LNCaP
      prostate cancer cell line. Western blot analysis showed that AR protein
      expression was inhibited by quercetin in a dose-dependent manner. To demonstrate
      that the repression effects on AR expression can actually reduce its function, we
      found that quercetin inhibited the secretion of the prostate-specific, androgen
      regulated tumor markers, PSA and hK2. The mRNA levels of androgen-regulated genes
      such as PSA, NKX3.1 as well as ornithine decarboxylase (ODC) were down-regulated
      by quercetin. Transient transfections further showed that quercetin inhibited AR
      mediated PSA expression at the transcription level. Finally, it was demonstrated
      that quercetin could repress the expression of the AR gene at the transcription
      level. Our result suggests that quercetin can attenuate the function of AR by
      repressing its expression and has the potential to become a chemopreventive
      and/or chemotherapeutic agent for prostate cancer.

PMID- 11238181
TI  - Human sensitivity to 1,3-butadiene: role of microsomal epoxide hydrolase
      polymorphisms.
AB  - 1,3-Butadiene (BD) is a major commodity chemical used in the manufacture of
      synthetic rubber and various plastics and has been shown to be a potent animal
      carcinogen and a probable human carcinogen. The bioactivation of BD to reactive
      epoxides, and the balance between activation and detoxication of these reactive
      metabolites, is thought to play a critical role in the genotoxic and carcinogenic
      effects of BD. The detoxication of reactive BD metabolites involves enzymatic
      conjugation with glutathione by glutathione S-transferases (GSTs) and by
      hydrolysis, a reaction mediated by microsomal epoxide hydrolase (mEH). Since
      polymorphisms in genes of xenobiotic-metabolizing enzymes such as mEH may
      influence individual susceptibility to adverse health effects from BD exposure,
      we tested the hypothesis that the mEH Tyr113His polymorphism increases
      sensitivity to the genotoxic effects of BD in exposed workers. We used the
      autoradiographic hprt mutant lymphocyte assay as a biomarker of effect to
      identify genotoxicity associated with BD exposure in 49 workers from two
      styrene/butadiene polymer plants in Southeast Texas. Exposure to BD was assessed
      by collecting breathing zone air samples using passive badge dosimeters for three
      full 12 h work shifts 25, 20 and 14 days before blood was collected for
      genotyping and for the hprt assay. We genotyped the study participants for the
      Tyr113His polymorphism in the mEH gene and also for deletion polymorphisms in the
      glutathione S-transferase genes, GSTM1 and GSTT1, as potential biomarkers of
      susceptibility to BD. Our data indicate that the majority of the study subjects
      (67%) were exposed to very low levels of BD of <150 parts per billion (p.p.b.)
      time-weighted average (TWA). In some workers, however, we found levels of BD
      exposures that exceeded a TWA of 2000 p.p.b. Our data indicate a significant (P <
      0.05) 2-fold increase in frequencies of hprt variant (mutant) lymphocytes (Vf) in
      workers exposed to >150 p.p.b. BD, compared with workers exposed to <150 p.p.b.
      There was no significant effect from individual GSTM1, GSTT1 or mEH genotypes in
      workers exposed to <150 p.p.b. BD. In workers exposed to >150 p.p.b., individuals
      with at least one polymorphic mEH His allele (His/His or His/Tyr genotypes) had a
      significant (P < 0.001) 3-fold increase in Vf (mean Vf x 10(-6) +/- SE = 13.25 +/
      1.78) compared with individuals with the Tyr/Tyr genotype (mean Vf x 10(-6) +/-
      SE = 4.02 +/- 0.72). There was no significant effect from individual GSTM1 or
      GSTT1 polymorphisms, but combined polymorphism analysis showed that the genetic
      damage was highest in individuals who had at least one mEH His allele and either
      the GSTM1 and/or GSTT1 null genotypes (hprt Vf = 14.19 +/- 2.30 x10(-6)). In
      contrast, this response was not observed in individuals exposed to levels of BD <
      150 p.p.b. These results indicate that polymorphisms in the mEH gene may play a
      significant role in human sensitivity to the genotoxic effects of BD exposure,
      and that the hprt mutant lymphocyte assay can serve as a sensitive biomarker of
      genotoxicity for monitoring occupational exposure to BD in industrial settings.
      Additional investigations in larger populations of workers are needed to confirm
      our results and to characterize the possible role of additional mEH polymorphisms
      in the induction of genetic damage associated with occupational exposure to
      butadiene.

PMID- 11238182
TI  - Molecular mechanism of rapid cellular accumulation of anticarcinogenic
      isothiocyanates.
AB  - Isothiocyanates (ITCs) are abundant in foods derived from vegetables, and many
      ITCs are potent cancer chemoprotective agents in animal systems. We previously
      showed that many ITCs rapidly accumulated in cells to very high concentrations
      (up to millimolar levels), and the accumulations appeared to play a critical role
      in determining their activities in inducing anticarcinogenic Phase 2 enzymes.
      Subsequent studies showed that ITCs were principally accumulated as glutathione
      (GSH) conjugates in cells and that cellular GSH might be the major driving force
      for ITC accumulation by undergoing conjugation with the entering ITCs. To
      elucidate the molecular mechanism responsible for the accumulation, the
      dependence of cellular ITC uptake on conjugation with GSH, as well as the role of
      cellular GSH transferases (GSTs) known to promote the conjugation was
      investigated. In addition, the role of ITC lipophilicity in ITC uptake was also
      addressed. All experiments were conducted with four dietary ITCs: allyl-ITC,
      benzyl-ITC, phenethyl-ITC and sulforaphane [1-isothiocyanato-(4R,S)
      (methylsulfinyl)butane]. Initial uptake rates of the four ITCs in human breast
      cancer cells (MCF-7) closely correlated with the non-enzymatic second-order rate
      constants of GSH conjugation reaction with the ITCs. Moreover, elevating cellular
      GSH levels also resulted in nearly proportional increases in cellular ITC uptake.
      In MCF-7 cells that overexpress human GST P1-1, the initial uptake rates of ITCs
      also increased linearly with an increase in the specific GST activity.
      Interestingly, lipophilicity of ITCs did not seem to influence ITC uptake by
      cells. Taken together, it is concluded that ITCs are taken up by cells
      predominantly, if not entirely, through GSH conjugation reactions in cells, and
      that cellular GST promotes ITC uptake by enhancing the conjugation reaction.

PMID- 11238183
TI  - Alcohol and aldehyde dehydrogenase gene polymorphisms and oropharyngolaryngeal,
      esophageal and stomach cancers in Japanese alcoholics.
AB  - Alcohol dehydrogenase-2 (ADH2) and aldehyde dehydrogenase-2 (ALDH2) gene
      polymorphisms play roles in ethanol metabolism, drinking behavior and esophageal
      carcinogenesis in Japanese; however, the combined influence of ADH2 and ALDH2
      genotypes on other aerodigestive tract cancers have not been investigated.
      ADH2/ALDH2 genotyping was performed on lymphocyte DNA samples from Japanese
      alcoholic men (526 cancer-free; 159 with solitary or multiple aerodigestive tract
      cancers, including 33 oropharyngolaryngeal, 112 esophageal, 38 stomach and 22
      multiple primary cancers in two or three organs). After adjustment for age,
      drinking and smoking habits, and ADH2/ALDH2 genotypes, the presence of either
      ADH2*1/2*1 or ALDH2*1/2*2 significantly increased the risk for
      oropharyngolaryngeal cancer [odds ratios (ORs), 6.68 with ADH2*1/2*1 and 18.52
      with ALDH2*1/2*2] and esophageal cancer (ORs, 2.64 and 13.50, respectively). For
      patients with both ADH2*1/2*1 and ALDH2*1/2*2, the risks for oropharyngolaryngeal
      and esophageal cancers were enhanced in a multiplicative fashion (OR = 121.77 and
      40.40, respectively). A positive association with ALDH2*1/2*2 alone was observed
      for stomach cancer patients who also had oropharyngolaryngeal and/or esophageal
      cancer (OR = 110.58), but it was not observed for those with stomach cancer
      alone. Furthermore, in the presence of ALDH2*1/2*2, the risks for multiple intra
      esophageal cancers (OR = 3.43) and for esophageal cancer with
      oropharyngolaryngeal and/or stomach cancer (OR = 3.95) were higher than the risks
      for solitary intra-esophageal cancer and for esophageal cancer alone, but these
      tendencies were not observed for ADH2*1/2*1 genotype. Alcoholics' population
      attributable risks due to ADH2/ALDH2 polymorphisms were estimated to be 82.0% for
      oropharyngolaryngeal cancer and 63.9% for esophageal cancer.

PMID- 11238184
TI  - Inhibition of N-nitrosomethylbenzylamine-induced tumorigenesis in the rat
      esophagus by dietary freeze-dried strawberries.
AB  - In the present study, we examined the ability of dietary freeze-dried
      strawberries to inhibit N-nitrosomethylbenzylamine (NMBA)-induced tumorigenesis
      in the rat esophagus. Initially, we conducted a bioassay to determine the effects
      of dietary freeze-dried strawberries on esophageal tumor development. Two weeks
      prior to NMBA treatment, animals were placed on a control diet or diets
      containing 5 and 10% freeze-dried strawberries. NMBA treatment was once per week
      for 15 weeks. At 30 weeks, 5 and 10% freeze-dried strawberries in the diet caused
      significant reductions in esophageal tumor multiplicity of 24 and 56%,
      respectively. Based on these results, we conducted studies to determine potential
      mechanisms by which freeze-dried strawberries inhibit tumorigenesis. In a short
      term bioassay, we evaluated the effects of dietary freeze-dried strawberries on
      the formation of O6-methylguanine in the rat esophagus. Animals were placed on
      control diet or diets containing 5 and 10% freeze-dried strawberries for two
      weeks. At the end of this period, animals received a single subcutaneous dose of
      NMBA and were killed 24 h later. A significant decrease in O6-methylguanine
      levels was observed in the esophageal DNA of animals fed strawberries, suggesting
      that one or more components in strawberries influence the metabolism of NMBA to
      DNA-damaging species. Finally, in order to evaluate post-initiation effects, we
      conducted a study where freeze-dried strawberries were administered in the diet
      only following NMBA treatment. Animals were placed on control diet and dosed with
      NMBA three times per week for 5 weeks. Immediately following NMBA treatment,
      animals were placed on control diet or diets containing 5 and 10% freeze-dried
      strawberries. At 25 weeks, 5 and 10% freeze-dried strawberries in the diet
      significantly reduced tumor multiplicity by 38 and 31%, respectively. Our data
      suggest that dietary freeze-dried strawberries effectively inhibit NMBA-induced
      tumorigenesis in the rat esophagus.

PMID- 11238185
TI  - Transforming growth factor-beta1-induced Smad signaling, cell-cycle arrest and
      apoptosis in hepatoma cells.
AB  - Transforming growth factor-beta1 (TGFbeta) is involved in the regulation of liver
      cell proliferation and apoptosis, and escape of hepatoma cells from the growth
      restraining signals of TGFbeta has been suggested to contribute to tumor
      development. TGFbeta modulates gene transcription by receptor-mediated activation
      of Smad proteins which act as transcription factors. TGFbeta-mediated primary
      signaling responses as well as effects on the cell cycle and apoptosis were
      investigated in the human hepatoblastoma line HepG2, the rat hepatoma line FTO-2B
      and the mouse hepatoma line 55.1c. Activation of a Smad (Sma and Mad homolog)
      response-element-driven luciferase reporter by TGFbeta was very similar in all
      three cell lines, indicating functionality of the primary TGFbeta signaling
      pathway. Moreover, TGFbeta-inducible early gene was transiently activated by
      TGFbeta in all cell lines as shown by RT-PCR. HepG2 cells, however, were
      completely resistant to TGFbeta-induced growth arrest and apoptosis and 55.1c
      cells were only slightly susceptible to TGFbeta-induced apoptosis. By contrast,
      treatment of FTO-2B cells with TGFbeta led to a partial G0/G1 arrest and a strong
      induction of apoptosis. TGFbeta-induced apoptosis of FTO-2B cells was inhibited
      by dexamethasone, insulin, phenobarbital and dieldrin. Of these agents, only
      insulin led to a significant reduction of TGFbeta-stimulated Smad-reporter
      activity, suggesting that the other compounds interfere with TGFbeta-induced
      apoptosis downstream of Smad-mediated primary transcriptional responses at a
      level that may be constitutively altered in apoptosis-resistant hepatoma cell
      lines.

PMID- 11238186
TI  - Differential metabolism of benzo[a]pyrene and benzo[a]pyrene-7,8-dihydrodiol by
      human CYP1A1 variants.
AB  - Cytochrome P450 1A1 (CYP1A1) plays a key role in the metabolism of carcinogens,
      such as benzo[a]pyrene (B[a]P) and metabolites to ultimate carcinogens. Three
      human allelic variants, namely wild-type (CYP1A1.1), CYP1A1.2 (I462V) and
      CYP1A1.4 (T461N), were coexpressed by coinfection of baculovirus-infected insect
      cells with human NADPH-P450 reductase. These recombinant enzymes (in microsomal
      membranes) were used to analyze whether CYP1A1 polymorphisms affect catalytic
      activities towards B[a]P and B[a]P-7,8-dihydrodiol. The complete spectrum of
      phase I metabolites, including the tetrahydrotetrols resulting from hydrolysis of
      the ultimate carcinogen, B[a]P-7,8-dihydrodiol-9,10-epoxide, was examined by
      HPLC. Wild-type enzyme showed the highest total metabolism of B[a]P, CYP1A1.2 was
      approximately 50%, and CYP1A1.4 approximately 70%. Km values for all metabolites
      with CYP1A1.2 were generally significantly lower than with wild-type enzyme (e.g.
      B[a]P-7,8-diol formation: 13.8 microM for wild-type, 3.5 microM for CYP1A1.2 and
      7.7 microM for CYP1A1.4). Addition of epoxide hydrolase markedly increases the
      relative diol-to-phenol activities by all three variants. However, CYP1A1.4
      exhibits the greatest efficiency to produce diol species. Each variant produced
      the diol epoxides from B[a]P-7,8-dihydrodiol. CYP1A1.1 exhibited with 10.4
      pmol/min/pmol CYP1A1 the greatest total rate for 7,8-diol metabolites followed by
      CYP1A1.2 (7.2 pmol/min/pmol CYP1A1) and CYP1A1.4 (5.5 pmol/min/pmol CYP1A1). All
      enzyme variants produced about three times more diol epoxide 2-derived
      metabolites than diol epoxide 1-derived ones, whereby both rare allelic variants
      exhibited statistically significantly increased formation of diol epoxide 2. This
      study showed that the three CYP1A1 variants had different enzyme kinetics
      properties to produce both the diol metabolites from B[a]P and the ultimate
      mutagenic species diol epoxide 2 from B[a]P-7,8-dihydrodiol, which must be
      considered in the evaluation of individual susceptibility to cancer.

PMID- 11238187
TI  - p16INK4a and beta-catenin alterations in rat liver tumors induced by NNK.
AB  - Inactivation of the p16INK4a (p16) tumor suppressor gene by promoter
      hypermethylation and mutation within exon 3 of beta-catenin represent two of the
      more common gene alterations in human hepatocellular carcinoma (HCC). One
      exposure implicated in the development of liver cancer is hepatitis B or C viral
      infection, which causes chronic destruction and regeneration of liver parenchyma.
      Treatment of rats with high doses of the tobacco-specific nitrosamine 4
      methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) also causes liver toxicity and a
      high incidence of tumors. The purpose of the current investigation was to define
      the prevalence of genetic alterations in p16 and beta-catenin in NNK-induced rat
      liver cancer to determine if the molecular mechanisms seen in human tumors are
      the same in this animal model. DNA isolated from 15 adenomas and 14 carcinomas
      was examined for methylation of p16 by methylation-specific PCR. p16 methylation
      was detected in five of 15 adenomas and eight of 14 carcinomas (45% of all
      tumors). Methylation of p16 was extensive within the 5'-untranslated region and
      exon 1alpha, areas shown to correlate with loss of gene transcription. Liver
      tumors were also screened for mutations within exon 3 of beta-catenin. Single
      strand conformation polymorphism and DNA sequencing revealed five mutations in
      four of 29 tumors (14%). Mutations were present in three adenomas and one
      carcinoma and were located within codons 33, 36 or 37. All mutations resulted in
      amino acid substitutions; three of these mutations occurred at potential serine
      phosphorylation sites. Our results link two important regulatory pathways altered
      in human HCC to cancer induced in the rat NNK model. The fact that common genetic
      alterations are observed between rodent and human HCC suggests that the rat NNK
      model could be useful for identifying additional genetic alterations critical to
      the initiation of HCC.

PMID- 11238188
TI  - Lack of chemopreventive effects of lycopene and curcumin on experimental rat
      prostate carcinogenesis.
AB  - The chemopreventive efficacy of lycopene and curcumin with regard to prostate
      carcinogenesis was investigated using 3,2'-dimethyl-4-aminobiphenol (DMAB)- and 2
      amino-1-methylimidazo[4,5-b]pyridine (PhIP)-induced rat ventral prostate cancer
      models. Three 60 week experiments with male F344 rats were carried out. In the
      first DMAB was given for the first 20 weeks and lycopene or curcumin were
      administered concomitantly or subsequently at dietary doses of 15 and 500 p.p.m.,
      respectively. In the second experiment lycopene and curcumin were given to rats
      pretreated with DMAB at doses of 5, 15 or 45 p.p.m. or 100 or 500 p.p.m. In the
      third PhIP was selected as an initiator for prostate carcinogenesis and
      administered for 20 weeks. Rats were then fed a diet containing lycopene at a
      dose of 45 p.p.m. or curcumin at a dose of 500 p.p.m. or both together.
      Chemopreventive effects of lycopene and curcumin on development of DMAB-induced
      ventral prostate carcinomas were observed only in the first experiment and no
      confirmation of inhibition potential was obtained in the following studies.
      Neither summational nor synergistic chemoprevention was evident. It is concluded
      from the present data that, overall, neither lycopene nor curcumin can
      consistently prevent rat prostate carcinogenesis.

PMID- 11238189
TI  - Beta-adrenergic growth regulation of human cancer cell lines derived from
      pancreatic ductal carcinomas.
AB  - Exocrine ductal carcinoma of the pancreas has been associated with smoking, and
      the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
      (NNK) causes this cancer type in laboratory rodents. Current knowledge on the
      growth regulation of this malignancy is extremely limited. Recent studies have
      shown overexpression of cyclooxygenase 2 (COX 2) and 5-lipoxygenase (5-lipox) in
      exocrine pancreatic carcinomas, suggesting a potential role of the arachidonic
      acid (AA) cascade in the regulation of this cancer type. In support of this
      interpretation, our data show high basal levels of AA release in two human cell
      lines derived from exocrine ductal pancreatic carcinomas. Both cell lines
      expressed m-RNA for beta2-adrenergic receptors and beta1-adrenergic receptors.
      Radio-receptor assays showed that beta2-adrenergic receptors predominated over
      beta1-adrenergic receptors. beta2-Adrenergic antagonist ICI118,551 significantly
      reduced basal AA release and DNA synthesis when the cells were maintained in
      complete medium. DNA synthesis of the cell line (Panc-1) with an activating point
      mutation in codon 12 of the ki-ras gene was significantly stimulated by NNK when
      cells were maintained in complete medium and this response was inhibited by the
      beta-blocker ICI118,551, the COX-inhibitor aspirin, or the 5-lipox-inhibitor MK
      886. The cell line without ras mutations (BXPC-3) did not show a significant
      response to NNK in complete medium. When the assays were conducted in serum-free
      medium, both cell lines demonstrated increased DNA synthesis in response to NNK,
      an effect inhibited by the beta2-blocker, aspirin, or MK-886. Panc-1 cells were
      more sensitive to the stimulating effects of NNK and less responsive to the
      inhibitors than BXPC-3 cells. Our findings are in accord with a recent report
      which has identified NNK as a beta-adrenergic agonist and suggest beta
      adrenergic, AA-dependent regulatory pathways in pancreatic cancer as a novel
      target for cancer intervention strategies.

PMID- 11238190
TI  - Cytochrome P450 expression and related metabolism in human buccal mucosa.
AB  - Constituents in food and fluids, tobacco chemicals and many drugs are candidates
      for oral absorption and oxidative metabolism. On this basis, the expression of
      cytochrome P450 isozymes (CYPs) and the conversion of CYP substrates were
      analysed in reference to buccal mucosa. A RT-PCR based analysis of human buccal
      tissue from 13 individuals demonstrated consistent expression of mRNA for the
      CYPs 1A1, 1A2, 2C, 2E1, 3A4/7 and 3A5. CYP 2D6 was expressed in six out of the 13
      specimens, whereas all samples were negative for 2A6 and 2B6. Serum-free
      monolayer cultures of the Siman virus 40 large T-antigen-immortalized SVpgC2a and
      the carcinoma SqCC/Y1 buccal keratinocyte lines expressed the same CYPs as tissue
      except 3A4/7 and 3A5 (SVpgC2a), and 2C, 2D6 and 3A4/7 (SqCC/Y1). Dealkylation of
      ethoxyresorufin and methoxyresorufin in both normal and transformed cells
      indicated functional 1A1 and 1A2, respectively. SVpgC2a showed similar activity
      as normal keratinocytes for both substrates, whereas SqCC/Y1 showed about 2-fold
      lower 7-ethoxyresorufin O-deethylation and 7-methoxyresorufin O-demethylation
      activities. SVpgC2a showed detectable and many-fold higher activity than the
      other cell types towards chlorzoxazone, a substrate for 2E1. Absent or minute
      catalytic activity of 2C9, 2D6 and 3A4 in the various cell types was indicated by
      lack of detectable diclofenac, dextromethorphan and testosterone metabolism (<0.2
      0.5 pmol/min/mg). Metabolic activation of the tobacco-specific N-nitrosamine 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and the mycotoxin aflatoxin B1
      (AFB1) to covalently bound adducts was indicated by autoradiographic analysis of
      both monolayer and organotypic cultures of SVpgC2a. In contrast, SqCC/Y1 showed
      lower or absent metabolic activity for these substrates. Finally, measurements of
      various non-reactive AFB1 metabolites indicated rates of formation <0.1
      pmol/min/mg in both normal and transformed cells. The results indicate presence
      of several CYPs of which some may contribute to significant xenobiotic metabolism
      in human buccal epithelium. Notably, metabolic activation of AFB1 was not
      previously implicated for oral mucosa. Further, the results show that CYP
      dependent metabolism can be preserved or even activated in immortalized
      keratinocytes. Metabolic activity in SVpgC2a under both monolayer and organotypic
      culture conditions suggests that this cell line may be useful to pharmaco
      toxicological and carcinogenesis studies.

PMID- 11238192
TI  - Metabolism of the beta-oxidized intermediates of N-nitrosodi-n-propylamine: N
      nitroso-beta-hydroxypropylpropylamine and N-nitroso-beta-oxopropylpropylamine.
AB  - The rat liver carcinogen N-nitrosodi-n-propylamine (NDPA) is metabolized to a
      propylating and methylating species in vivo. Metabolism to a methylating species
      is believed to require an initial hydroxylation by cytochrome P450s (P450s) to N
      nitroso-beta-hydroxypropylpropylamine (NHPPA), which is oxidized to N-nitroso
      beta-oxopropylpropylamine (NOPPA), followed by a P450-mediated depropylation to
      beta-oxopropyldiazotate, which non-enzymatically breaks down to the methylating
      agent. Purified rat liver P450 2B1 and rabbit liver 2E1 in the reconstituted
      system and liver microsomes from phenobarbital (PB) and pyridine (Pyr) treated
      rats readily metabolized NOPPA to a methylating species as determined by the in
      vitro formation of 7-methylguanine (m7Gua) in DNA. Exposure of cells derived from
      the human liver epithelium transfected with human 2E1 (T5-2E1) to NOPPA resulted
      in the formation of m7Gua DNA adducts and a dose dependent toxicity. In vitro
      incubation of NHPPA with microsomes from PB, Pyr and non-treated (NT) rats and a
      human microsomal sample also resulted in m7Gua formation. P450s 2B1 and 2E1
      oxidized NHPPA to NOPPA, forming 16.5 +/- 3.1 and 20.0 +/- 4.4 pmol NOPPA/pmol
      P450 in 1 h, respectively. Rat liver cytosol, in the presence of NAD+, oxidized
      NHPPA to NOPPA at a rate of 13.7 +/- 3.0 pmol/min/mg protein while microsomes
      from NT rats catalyzed this reaction at 95.6 +/- 16.5 pmol/min/mg protein. Cells
      derived from hamster lung tissue (V79 control) and T5-neo cells oxidized NHPPA to
      NOPPA. This oxidation was about 15 fold higher in T5-2E1 or V79 cells transfected
      with human 2E1 or rat 2B1, respectively. The results are consistent with the
      putative sequential oxidation pathway and suggest that, at the concentrations
      tested, oxidation of NHPPA to NOPPA may be predominantly mediated by cytochrome
      P450s. In addition, it appears that rabbit, rat and human P450 2E1 can catalyze
      both oxidations.

PMID- 11238191
TI  - Catechol estrogen conjugates and DNA adducts in the kidney of male Syrian golden
      hamsters treated with 4-hydroxyestradiol: potential biomarkers for estrogen
      initiated cancer.
AB  - Formation of depurinating adducts by reaction of catechol estrogen-3,4-quinones
      with DNA was proposed to be a tumor initiating event by estrogens [E.L. Cavalieri
      et al. (1997) Proc. Natl Acad. Sci. USA, 94, 10937-10942]. Under estrogenic
      imbalance, oxidation of catechol estrogens to quinones may compete with their
      detoxification by protective enzymes. The quinones formed can be detoxified by
      reaction with glutathione (GSH) or can covalently bind to DNA. To provide more
      support for this hypothesis, we developed a method to identify and quantify GSH,
      cysteine (Cys) and N-acetylCys conjugates of 4-hydroxyestrogens (4-OHE) in the
      kidneys of male Syrian hamsters treated with 4-hydroxyestradiol (4-OHE2) by
      intraperitoneal injection. The highest level of conjugates was observed 1 h after
      treatment, and almost none was detected after 24 h. Dose-response studies
      indicated conjugate formation after treatment with 0.5 micromol of 4-OHE2/100 g
      body weight, and formation increased up to a treatment level of 12 micromol/100 g
      body weight. GSH, Cys and N-acetylCys conjugates of 4-OHE were identified in the
      picomole range by high-performance liquid chromatography (HPLC) with multichannel
      electrochemical detection and confirmed by HPLC/tandem mass spectrometry.
      Treatment of tissue homogenates with beta-glucuronidase/sulfatase at 37 degrees C
      for 6 h before extraction resulted in a 12- to 20-fold increase in Cys conjugates
      from picomole to nanomole levels. Similar enhancement was observed by just
      incubating the tissue at 37 degrees C for 6 h. Evidence for the 4-OHE-1-N7Gua
      depurinating adducts was obtained by mass spectrometry. We conclude that GSH and
      Cys conjugates of the 4-OHE and the 4-OHE-N7Gua adducts can be utilized as
      biomarkers to detect estrogenic imbalance and potential susceptibility to tumor
      initiation.

PMID- 11238193
TI  - Rat gap junction connexin-30 inhibits proliferation of glioma cell lines.
AB  - Connexins, the structural components of gap junctions, control cell growth and
      differentiation and are believed to belong to a family of tumour suppressor
      genes. Studies on connexin localization in brain showed that several of these
      proteins were expressed in distinct compartments of the brain in a cell-type
      specific manner, indicating that different gap junctions play specific roles in
      the physiology of the mammalian brain. In this report, we first cloned rat
      connexin-30 cDNA from brain and showed that it was expressed in long-term primary
      culture of rat astrocytes. In order to examine the potential role of connexin-30
      in tumour cell proliferation, we transfected the connexin-30 cDNA into two rat
      glioma cell lines (9L and C6) which have lost its expression. Transfected clones
      adequately expressed membrane-bound connexin-30 protein. Connexin-30-expressing
      clones showed slower growth, lower DNA synthesis and reduced proliferation in
      soft agar as compared with the parental and control cells. We concluded that
      connexin-30 may also probably be considered as a tumour suppressor in rat
      gliomas.

PMID- 11238194
TI  - Inactivate the remaining p53 allele or the alternate p73? Preferential selection
      of the Arg72 polymorphism in cancers with recessive p53 mutants but not
      transdominant mutants.
AB  - Several reports have noted epidemiological differences in the prevalence or
      prognostic significance of p53 mutants with arginine (R) or proline (P) at the
      codon 72 polymorphism (R72/P72) in certain cancer types, but the biological
      significance of these variants is unclear. The ability of p53 mutants to interact
      with and inactivate the p53 homolog p73 was recently reported to depend on the
      conformational state of the p53 protein and the residue at codon 72. Since the
      conformation of p53 mutants may influence their ability to transdominantly
      inhibit wild-type p53, we tested whether there was a correlation between the
      amino acid at codon 72 and the transdominance of p53 alleles found in tumors. The
      transdominance test was performed using a simple yeast transcription assay, and
      the amino acid at codon 72 was determined by sequencing. A total of 100 p53
      mutants were tested. Compared with the germline frequency (R:P = 427:297), an
      extreme bias in favor of the R72 allele was observed with recessive mutants (R:P
      = 50:7, P < 0.0002), whereas no selection for the R72 allele was seen with
      transdominant mutants (R:P = 23:20). p53 and p73 are known to transactivate
      overlapping sets of target genes. We interpret the R72 bias with recessive
      mutants as evidence that decreased activation of p53 target genes provides a
      selective growth advantage to tumor cells during the stage of tumorigenesis in
      which a wild-type and mutant p53 allele coexist. We suggest that transdominant
      p53 mutants achieve this by inactivation of the remaining wild-type p53 allele,
      whereas recessive p53 mutants achieve it through inactivation of p73.

PMID- 11238195
TI  - Peroxisome proliferators do not increase DNA synthesis in purified rat
      hepatocytes.
AB  - There have been numerous reports that chemicals which induce peroxisomes in
      rodent liver increase DNA synthesis in isolated hepatic parenchymal cells, but
      not as well in vitro as in vivo. It is also known that tumour necrosis factor
      alpha (TNFalpha) is mitogenic in isolated hepatocytes. Since Kupffer cells are a
      major source of TNFalpha in the liver and have recently been shown to be
      activated by peroxisome proliferators, the possibility exists that the effect of
      peroxisome proliferators on DNA synthesis in parenchymal cells is via Kupffer
      cell contamination of isolated hepatocyte preparations. The purpose of this study
      was to evaluate this hypothesis by studying the effect of model peroxisome
      proliferators on purified hepatocyte preparations. Hepatocytes were prepared from
      rat liver by standard calcium-free and collagenase perfusion. Subsequently, cells
      were centrifuged through Percoll to remove contaminating non-parenchymal cells.
      Cells were at least 99.9% pure as assessed by cell counting using specific
      markers for hepatocytes (resorufin O-glucoside) and Kupffer cells (FITC-labelled
      latex beads). Hepatocytes were cultured in Williams medium + 10% fetal bovine
      serum for 24 h followed by culture for 48 h in Williams medium plus or minus drug
      or mitogen additions. Under these conditions epidermal growth factor stimulated
      DNA synthesis assessed by incorporation of [3H]thymidine approximately 5-fold
      over control levels. The peroxisome proliferators WY,14-643 and nafenopin,
      however, had no effect on DNA synthesis, although they did increase acyl-CoA
      oxidase as expected. In contrast, TNFalpha increased cell proliferation nearly 10
      fold in purified hepatocytes, an effect nearly doubled by WY-14,643. Further,
      when conditioned medium from purified Kupffer cells incubated with WY-14,643 was
      added to pure hepatocytes, DNA synthesis was increased over 2-fold in a time
      dependent manner. Collectively, these data support the hypothesis that peroxisome
      proliferators do not influence DNA synthesis in isolated hepatocytes per se.
      Rather, they stimulate cytokine production by Kupffer cells which in turn
      increases DNA synthesis in parenchymal cells. An increase in mitogenic cytokine
      production by Kupffer cells is necessary for stimulation of DNA synthesis in
      purified rat parenchymal cells.

PMID- 11238196
TI  - Slow-release pellets of sodium butyrate do not modify azoxymethane (AOM)-induced
      intestinal carcinogenesis in F344 rats.
AB  - Butyrate exerts anti-tumour effects in vitro, but not consistently in vivo. We
      previously demonstrated that the administration of slow-release gastro-resistant
      pellets of sodium butyrate increases apoptosis in the colon mucosa of rats, an
      effect which may protect against carcinogenesis. Therefore, we studied whether
      the administration of butyrate pellets could protect rats against experimental
      colon carcinogenesis. Four to 5 week old male F344 rats were fed a high-fat (HF)
      diet (230 g/kg corn oil w/w) and treated s.c. with two injections (one week
      apart) of azoxymethane (AOM) at a dose rate of 15 mg/kg body weight or saline.
      Rats were then divided into two groups: one group received sodium butyrate
      pellets mixed into the diet (1.5% w/w) for 33 weeks (150 mg butyrate/day) and the
      second group received the high-fat diet with no butyrate. Administration of
      sodium butyrate pellets in the diet did not significantly affect colon
      carcinogenesis: the number of intestinal tumours/rat was 1.6 +/- 0.2 in controls
      and 2.1 +/- 0.2 in butyrate-fed rats (means +/- SE; P = 0.22, by ANOVA), while
      the incidence of intestinal tumours was 79 (23/29) and 90% (27/30) in controls
      and in butyrate-fed rats, respectively (P = 0.29 by Fisher's exact test). The
      level of apoptosis in the tumours was not affected by butyrate, nor was the
      expression of p21(CIP), a cell cycle-related protein. In conclusion, the current
      study indicates that butyrate does not protect against AOM-induced colon
      carcinogenesis in rats.

PMID- 11238197
TI  - Re: Henderson,B.E. and Feigelson,H.S. (2000) hormonal carcinogenesis.
      Carcinogenesis, 21, 427-433.

PMID- 11238199
TI  - PCR-based detection, restriction endonuclease analysis, and transcription of tonB
      in Haemophilus influenzae and Haemophilus parainfluenzae isolates obtained from
      children undergoing tonsillectomy and adenoidectomy.
AB  - We developed and evaluated a PCR-based-restriction endonuclease analysis method
      to detect and analyze the tonB gene of Haemophilus influenzae and Haemophilus
      parainfluenzae from pediatric patients undergoing tonsillectomy and
      adenoidectomy. Multiple sites from the same patient, including the surface of
      adenoids and tonsils, as well as the core of tonsils, were cultured on chocolate
      agar and identified using standard procedures and the API NH Kit. A total of 55
      H. influenzae isolates were recovered from different sites of 20 patients, and 32
      H. parainfluenzae isolates were recovered from various sites of 12 patients. DNA
      was extracted from American Type Culture Collection strains and test isolates by
      the PureGene kit. Two primers, G1 (21-mer) and G2 (23-mer), were designed by us
      to amplify by PCR the tonB gene that consists of an 813-bp fragment. A nested PCR
      using primers T1 (23-mer) and T2 (24-mer) that flank an internal sequence to the
      gene of the order of 257 bp and restriction endonuclease digestion using XhoI and
      BglII were done to detect whether heterogeneity within the gene exists between
      the two species. Reverse transcription-PCR (RT-PCR) was finally done to detect
      transcription of the gene in both species. Our data have shown that the tonB gene
      was detected in both species. It is known to encode a virulent protein, TonB, in
      H. influenzae; however, demonstration of its presence in H. parainfluenzae is
      novel. Nested-PCR and restriction endonuclease analysis have shown that the tonB
      gene is apparently structurally the same in both species, with possible
      differences that may exist in certain H. parainfluenzae isolates. RT-PCR done on
      selected numbers of H. influenzae and H. parainfluenzae have shown that the tonB
      gene was transcribed in both species. This shows that the TonB protein, if
      expressed, may play a different role in the virulence in H. parainfluenzae since
      it is not needed for heme or heme complexes uptake as with H. influenzae.

PMID- 11238200
TI  - Lyme borreliosis in rhesus macaques: effects of corticosteroids on spirochetal
      load and isotype switching of anti-borrelia burgdorferi antibody.
AB  - Experimental Borrelia burgdorferi infection of rhesus monkeys is an excellent
      model of Lyme disease and closely parallels the infection in humans. Little is
      known about the interaction of host immunity with the spirochete in patients with
      chronic infection. We hypothesized that rapid development of anti-B. burgdorferi
      antibody in immunocompetent nonhuman primates (NHPs) is the major determinant of
      the reduction of the spirochetal load in Lyme borreliosis. This hypothesis was
      tested by measurement of the spirochetal load by PCR in association with
      characterization of the anti-B. burgdorferi humoral immune response in
      immunocompetent NHPs versus that in corticosteroid-treated NHPs. Although anti-B.
      burgdorferi immunoglobulin G (IgG) antibody was effectively inhibited in
      dexamethasone (Dex)-treated NHPs, anti-B. burgdorferi IgM antibody levels
      continued to rise after the first month and reached levels in excess of IgM
      levels in immunocompetent NHPs. This vigorous production of anti-B. burgdorferi
      IgM antibodies was also studied in vitro by measurement of antibody produced by
      B. burgdorferi-stimulated peripheral blood mononuclear cells. Despite these high
      IgM antispirochetal antibodies in Dex-treated NHPs, spirochetal loads were much
      higher in these animals. These data indicate that Dex treatment results in
      interference with isotype switching in this model and provide evidence that anti
      B. burgdorferi IgG antibody is much more effective than IgM antibody in
      decreasing the spirochetal load in infected animals.

PMID- 11238201
TI  - Up-regulation of CD40 ligand and induction of a Th2 response in children
      immunized with pneumococcal polysaccharide vaccines.
AB  - We wished to determine whether pneumococcal polysaccharide antigens induce mRNA
      expression of CD40 ligand (CD40L) and Th1 or Th2 cytokines in unimmunized
      individuals in vitro and whether immunization with the 23-valent pneumococcal
      polysaccharide vaccine induces changes in CD40L and cytokine mRNA expression.
      Children with recurrent respiratory infections were studied before and 4 to 6
      weeks after receiving the pneumococcal vaccine. One patient who failed to respond
      to the polysaccharide vaccine subsequently received a single dose of the
      experimental 7-valent pneumococcal conjugate vaccine. Unimmunized healthy adults
      were included as controls. Quantification of mRNA expression of CD40L,
      interleukin-4 (IL-4), IL-12p40, and gamma interferon (IFN-gamma) was performed by
      reverse transcription-PCR and enzyme-linked immunosorbent assay (ELISA)-PCR with
      resting and stimulated peripheral blood mononuclear cells. Serum immunoglobulin G
      (IgG) anti pneumococcal antibody levels were measured by ELISA. The results
      showed a significant increase in the expression of mRNAs for CD40L and IL-4, but
      not IL-12p40 or IFN-gamma, in stimulated cultures from unimmunized individuals.
      CD40L and IL-4 mRNA expression was significantly higher in postimmunization than
      in preimmunization samples stimulated with the individual pneumococcal serotypes.
      These results suggest that pneumococcal polysaccharide antigens specifically up
      regulate CD40L expression and induce a Th2 response in vitro which parallels the
      increase in IgG antipneumococcal antibody levels in serum.

PMID- 11238198
TI  - Cell-mediated immune response to human papillomavirus infection.

PMID- 11238202
TI  - Analysis of the 16S rRNA gene sequence of Anaplasma centrale and its phylogenetic
      relatedness to other ehrlichiae.
AB  - The nucleotide sequence of the Anaplasma centrale 16S rRNA gene was determined
      and compared with the sequences of ehrlichial bacteria. The sequence of A.
      centrale was closely related to Anaplasma marginale by both level-of-similarity
      (98.08% identical) and distance analysis. A species-specific PCR was developed
      based upon the alignment data. The PCR can detect A. centrale DNA extracted from
      10 infected bovine red blood cells in a reaction mixture. A. centrale DNA was
      amplified in the reaction, but not other related ehrlichial species.

PMID- 11238203
TI  - Comparison of a classical phagocytosis assay and a flow cytometry assay for
      assessment of the phagocytic capacity of sera from adults vaccinated with a
      pneumococcal conjugate vaccine.
AB  - Antibody- and complement-mediated phagocytosis is the main defense mechanism
      against Streptococcus pneumoniae. A standardized, easy to perform phagocytosis
      assay for pneumococci would be a great asset for the evaluation of the potential
      efficacy of (experimental) pneumococcal vaccines. Such an assay could replace the
      laborious phagocytosis assay of viable pneumococci (classical killing assay).
      Therefore, a newly developed phagocytosis assay based on flow cytometry (flow
      assay) was compared with the conventional killing assay and enzyme-linked
      immunosorbent assay (ELISA), using sera obtained from adults pre- and
      postvaccination with either a bivalent conjugate, a tetravalent conjugate, or the
      23-valent polysaccharide vaccine. Highly significant correlations were observed
      between flow assay phagocytosis titers, killing assay phagocytosis titers, and
      ELISA antibody titers for serotype 6B and 23F as well. For serotype 19F, strong
      correlations were only observed between killing assay and ELISA titers. A
      potential drawback of the flow assay might be the low sensitivity compared with
      that of the killing assay. The choice of what assay to use, however, will depend
      on the objectives of the assay. When speed, easy performance, sample throughput,
      improved worker safety, absence of influence of antibiotics, and absence of false
      positives are the major criteria, the flow assay is the method of choice. When
      higher sensitivity is the major requirement, the classical killing assay should
      be used.

PMID- 11238204
TI  - Cloning and characterization of the gene encoding the glutamate dehydrogenase of
      Streptococcus suis serotype 2.
AB  - Given the lack of effective vaccines to control Streptococcus suis infection and
      the lack of a rapid and reliable molecular diagnostic assay to detect its
      infection, a polyclonal antibody was raised against the whole-cell protein of S.
      suis type 2 and used to screen an S. suis gene library in an effort to identify
      protective antigen(s) and antigens of diagnostic importance. A clone that
      produced a 45-kDa S. suis-specific protein was identified by Western blotting.
      Restriction analysis showed that the gene encoding the 45-kDa protein was present
      on a 1.6-kb pair DraI region on the cloned chromosomal fragment. The nucleotide
      sequence contained an open reading frame that encoded a polypeptide of 448 amino
      acid residues with a calculated molecular mass of 48.8 kDa, in close agreement
      with the size observed on Western blots. A GenBank database search revealed that
      the derived amino acid sequence is homologous to the sequence of glutamate
      dehydrogenase (GDH) protein isolated from various sources, including conserved
      motifs and functional domains typical of the family 1-type hexameric GDH
      proteins, thus placing it in that family. Because of these similarities, the
      protein was designated the GDH of S. suis. Hybridization studies showed that the
      gene is conserved among the S. suis type 2 strains tested. Antiserum raised
      against the purified recombinant protein was reactive with a protein of the same
      molecular size as the recombinant protein in S. suis strains, suggesting
      expression of the gene in all of the isolates and antigenic conservation of the
      protein. The recombinant protein was reactive with serum from pigs experimentally
      infected with a virulent strain of S. suis type 2, suggesting that the protein
      might serve as an antigen of diagnostic importance to detect S. suis infection.
      Activity staining showed that the S. suis GDH activity is NAD(P)H dependent but,
      unlike the NAD(P)H-dependent GDH from various other sources, that of S. suis
      utilizes L-glutamate rather than alpha-ketoglutarate as the substrate. Highly
      virulent strains of S. suis type 2 could be distinguished from moderately
      virulent and avirulent strains on the basis of their GDH protein profile
      following activity staining on a nondenaturing gel. We examined the cellular
      location of the protein using a whole-cell enzyme-linked immunosorbent assay and
      an immunogold-labeling technique. Results showed that the S. suis GDH protein is
      exposed at the surface of intact cells.

PMID- 11238206
TI  - Pneumococcal type 22f polysaccharide absorption improves the specificity of a
      pneumococcal-polysaccharide enzyme-linked immunosorbent assay.
AB  - The specificity of the immune response to the 23-valent pneumococcal
      polysaccharide (PS) vaccine in healthy adults and to a pneumococcal conjugate
      vaccine in infants was examined by measuring immunoglobulin G (IgG) antibody
      titers by enzyme-linked immunosorbent assay (ELISA) and the opsonophagocytosis
      assay. ELISA measures total antipneumococcal IgG titers including the titers of
      functional and nonfunctional antibodies, while the opsonophagocytosis assay
      measures only functional-antibody titers. Twenty-four pairs of pre- and post
      pneumococcal vaccination sera from adults were evaluated (ELISA) for levels of
      IgG antibodies against serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. Twelve of the
      pairs were also examined (opsonophagocytosis assay) for their functional
      activities. The correlation coefficients between assay results for most types
      ranged from 0.75 to 0.90, but the correlation coefficient was only about 0.6 for
      serotypes 4 and 19F. The specificities of these antibodies were further examined
      by the use of competitive ELISA inhibition. A number of heterologous
      polysaccharides (types 11A, 12F, 15B, 22F, and 33A) were used as inhibitors. Most
      of the sera tested showed cross-reacting antibodies, in addition to those removed
      by pneumococcal C PS absorption. Our data suggest the presence of a common
      epitope that is found on most pneumococcal PS but that is not absorbed by
      purified C PS. Use of a heterologous pneumococcal PS (22F) to adsorb the
      antibodies to the common epitope increased the correlation between the IgG ELISA
      results and the opsonophagocytosis assay results. The correlation coefficient
      improve from 0.66 to 0.92 for type 4 and from 0.63 to 0.80 for type 19F. These
      common-epitope antibodies were largely absent in infants at 7 months of age,
      suggesting the carbohydrate nature of the epitope.

PMID- 11238205
TI  - Adherence of Giardia lamblia trophozoites to Int-407 human intestinal cells.
AB  - Attachment of Giardia lamblia trophozoites to enterocytes is essential for
      colonization of the small intestine and is considered a prerequisite for parasite
      induced enterocyte dysfunction and clinical disease. In this work, coincubation
      of Giardia with Int-407 cells, was used as an in vitro model to study the role of
      cytoskeleton and surface lectins involved in the attachment of the parasite. This
      interaction was also studied by scanning and transmission electron microscopy.
      Adherence was dependent on temperature and was maximal at 37 degrees C. It was
      reduced by 2.5 mM colchicine (57%), mebendazole (10 microg/ml) (59%), 100 mM
      glucose (26%), 100 mM mannose (22%), 40 mM mannose-6-phosphate (18%), and
      concanavalin A (100 microg/ml) (21%). No significant modification was observed
      when Giardia was pretreated with cytochalasins B and D and with EDTA. Giardia
      attachment was also diminished by preincubating Int-407 cells with cytochalasin B
      and D (5 microg/ml) (16%) and by glutaraldehyde fixation of intestinal cells and
      of G. lamblia trophozoites (72 and 100%, respectively). Ultrastructural studies
      showed that Giardia attaches to the Int-407 monolayer predominantly by its
      ventral surface. Int-407 cells contact trophozoites with elongated microvilli,
      and both trophozoite imprints and interactions of Giardia flagella with
      intestinal cells were also observed. Transmission electron microscopy showed that
      Giardia lateral crest and ventrolateral flange were important structures in the
      adherence process. Our results suggest a combination of mechanical and
      hydrodynamic forces in trophozoite attachment; surface lectins also seem to
      mediate binding and may be involved in specific recognition of host cells.

PMID- 11238208
TI  - Quantification of bacterial transcripts during infection using competitive
      reverse transcription-PCR (RT-PCR) and LightCycler RT-PCR.
AB  - Bacteria have evolved sophisticated regulatory circuits to modulate their gene
      expression in response to disparate environments. In order to monitor bacterial
      gene expression and regulation in the host, methods for direct transcript
      analysis from clinical specimens are needed. For most bacterial infections,
      amplification of the mRNAs of interest is necessary due to the low numbers of
      cells present and the low levels of specific transcripts. Here we compare two
      methods of quantitative reverse transcription-PCR (RT-PCR)-competitive RT-PCR
      using a one-tube system followed by standard gel analysis and the real-time
      detection of PCR product formation by fluorescence resonance energy transfer
      technology using the LightCycler unit. We isolated Staphylococcus aureus RNA
      directly from clinical specimens obtained from cystic fibrosis patients with
      chronic S. aureus lung infection and from an animal model of foreign-body
      infection with no further cultivation of the bacteria. Competitive RT-PCR and
      LightCycler RT-PCR were tested for their ability to quantify the transcription of
      a constitutively expressed gyrase gene (gyr) and a highly regulated alpha-toxin
      gene (hla) of S. aureus. Reproducible results were obtained with both methods. A
      sensitivity of 10(4) (gyr) and 10(3) (hla) copies, respectively, was reached,
      which was sufficient for the quantification of transcripts during bacterial
      infection. Overall, the competitive RT-PCR is a robust technique which does not
      need special RNA purification. On the negative side, it is labor intensive and
      time consuming, thus limiting the numbers of samples which can be analyzed at a
      given time. LightCycler RT-PCR is very susceptible to even traces of inhibitors,
      but it allows high-throughput processing of samples.

PMID- 11238207
TI  - Performance of antigens used in detecting delayed-type hypersensitivity in
      adolescents infected with the human immunodeficiency virus.
AB  - We examined the performance of delayed-type hypersensitivity (DTH) antigens
      employing a new Candida albicans product in a human immunodeficiency virus (HIV)
      infected and nonanergic adolescent population. Diameters of induration (in
      millimeters) for three intradermally applied antigens (C. albicans, tetanus
      toxoid, and mumps) were compared in a population of HIV-infected 12 to 18 year
      olds at study entry in a national multicenter study of HIV disease progression.
      CD4+ T-cell counts were measured in quality-controlled laboratories. The
      influence of past immunization, gender, and clinical status on antigen reactivity
      was evaluated with contingency table comparisons and relative risk estimation.
      Nearly one-half of the 123 eligible subjects were untreated, and almost three
      quarters were early in HIV disease by clinical indicators. There was no
      statistically significant difference in reactivity by past immunization status.
      Candida antigen (CASTA; Greer Laboratories) evoked DTH response in a
      significantly higher number of males and females at every level of induration
      (largest P value, 0.049 for male comparisons; all P values, <0.001 for females)
      and in subjects with early and intermediate HIV disease at every level of
      induration (all P values, <0.0001) than either tetanus or mumps antigens. No two
      antigen combination was as useful as all three antigens across either gender or
      clinical categories, although candida and tetanus was the most useful two-antigen
      combination at indurations of <3 mm. The superior performance of a new C.
      albicans antigen may extend the utility of DTH assessment in monitoring immune
      function.

PMID- 11238209
TI  - Differentiation of two bovine lentiviruses by a monoclonal antibody on the basis
      of epitope specificity.
AB  - Bovine immunodeficiency virus (BIV) and Jembrana disease virus (JDV) are bovine
      lentiviruses that are closely related genetically. A recombinant fusion protein
      containing the capsid protein of BIV expressed in Escherichia coli was used to
      immunize mice and produce monoclonal antibodies. Six hybridomas specific for BIV
      capsid protein were identified, and one antibody, designated 10H1, was
      characterized further. Competitive binding assays were performed to analyze the
      topography of antigenic determinants by enzyme-linked immunosorbent assay and
      demonstrated the existence of at least three distinct antigenic determinants on
      capsid protein. The monoclonal antibody reacted specifically with both BIV capsid
      and the recombinant fusion protein in Western immunoblot analyses. However, it
      did not react with the recombinant capsid fusion protein of JDV, indicating that
      BIV contains at least one unique epitope in the capsid protein that is absent in
      JDV. Further mapping of the epitope by chemical cleavage analysis identified that
      the epitope is located at the 6.4-kDa N terminus of the 29-kDa capsid protein.
      This monoclonal antibody assay will be valuable for distinguishing the two
      closely related lentiviruses by Western blotting.

PMID- 11238210
TI  - Placental cellular immune response in women infected with human parvovirus B19
      during pregnancy.
AB  - Human parvovirus B19 can cause congenital infection with variable morbidity and
      mortality in the fetus and neonate. Although much information exists on the B19
      specific antibody response in pregnant women, little information is available
      describing the cell-mediated immune (CMI) response at the maternal-fetal
      interface. The focus of this study was to characterize the CMI response within
      placentas from women who seroconverted to B19 during their pregnancies and
      compare it to controls. Immunohistochemical techniques were used to identify the
      various immune cells and the inflammatory cytokine present within placental
      tissue sections. Group 1 consisted of placentas from 25 women whose pregnancies
      were complicated by B19 infection; 6 women with good outcome (near-term or term
      delivery), and 19 with poor outcome (spontaneous abortion, nonimmune hydrops
      fetalis, or fetal death). Group 2 consisted of placentas from 20 women whose
      pregnancies were complicated with nonimmune hydrops fetalis of known,
      noninfectious etiology. Group 3 consisted of placentas from eight women whose
      pregnancies ended in either term delivery or elective abortion. The results of
      the study revealed a statistically significant increase in the number of CD3
      positive T cells present within placentas from group 1 compared to group 2 or 3
      (13.3 versus 2 and 1, respectively) (P < 0.001). In addition, the inflammatory
      cytokine interleukin 2 was detected in every placenta within group 1 but was
      absent from all placentas evaluated from groups 2 and 3. Together, these findings
      demonstrate evidence for an inflammation-mediated cellular immune response within
      placentas from women whose pregnancies are complicated with B19 infection.

PMID- 11238211
TI  - Adherence of probiotic bacteria to human intestinal mucus in healthy infants and
      during rotavirus infection.
AB  - The concentration of fecal mucin and the adhesion of specific probiotics and
      their combinations in the intestinal mucus of infants during and after rotavirus
      diarrhea and in healthy children were determined. Mucus was prepared from fecal
      samples from 20 infants during and after rotavirus diarrhea and from 10 healthy
      age-matched children. Mucin concentration was determined, and the adhesion of
      five probiotics-Lactobacillus rhamnosus GG, Lactobacillus casei Shirota,
      Lactobacillus paracasei F19, Lactobacillus acidophilus LA5, and Bifidobacterium
      lactis Bb12-and their combinations was tested in vitro. The mean concentrations
      of fecal mucin during and after rotavirus diarrhea, 15.2 and 14.1 mg/g, were
      comparable to that in healthy children, 14.9 mg/g. The adherence of probiotics
      ranged from 1 to 34% in healthy subjects as indicated for the following strains:
      L. rhamnosus GG, 34%; B. lactis Bb12, 31%; L. acidophilus LA5, 4%; L. paracasei
      F19, 3%; and L. casei Shirota, 1% (P = 0.0001). The distinctive pattern of
      probiotic adherence was not influenced by rotavirus diarrhea. The adhesion of
      Bb12 in the presence of GG increased from 31 to 39% in healthy infants (P =
      0.018) and in episodes of diarrhea increased from 26 to 44% (P = 0.001).
      Rotavirus diarrhea does not decrease the production of fecal mucin or with
      respect to the adhesion of probiotic bacteria tested in vitro. Combination of
      specific probiotic strains may enhance adherence in a synergistic manner. Optimal
      clinical application of these interactions may offer novel therapeutic guidelines
      for the treatment and prevention of gastrointestinal infections.

PMID- 11238212
TI  - A single amino acid change within antigenic domain II of the spike protein of
      bovine coronavirus confers resistance to virus neutralization.
AB  - The spike glycoprotein is a major neutralizing antigen of bovine coronavirus
      (BCV). Conformational neutralizing epitopes of group A and group B monoclonal
      antibodies (MAbs) have previously been mapped to two domains at amino acids 351
      to 403 (domain I) and amino acids 517 to 621 (domain II). To further map
      antigenic sites, neutralization escape mutants of BCV were selected with a group
      A MAb which has both in vitro and in vivo virus-neutralizing ability. The escape
      mutants were demonstrated to be neutralization resistant to the selecting group A
      MAb and remained sensitive to neutralization by a group B MAb. In
      radioimmunoprecipitation assays, the spike proteins of neutralization escape
      mutants were shown to have lost their reactivities with the selecting group A
      MAb. Sequence analysis of the spike protein genes of the escape mutants
      identified a single nucleotide substitution of C to T at position 1583, resulting
      in the change of alanine to valine at amino acid position 528 (A528V). The
      mutation occurs in domain II and in a location which corresponds to the
      hypervariable region of the spike protein of the coronavirus mouse hepatitis
      virus. Experimental introduction of the A528V mutation into the wild-type spike
      protein resulted in the loss of MAb binding of the mutant protein, confirming
      that the single point mutation was responsible for the escape of BCV from
      immunological selective pressure.

PMID- 11238213
TI  - Three-color flow cytometry detection of intracellular cytokines in peripheral
      blood mononuclear cells: comparative analysis of phorbol myristate acetate
      ionomycin and phytohemagglutinin stimulation.
AB  - The assessment of intracellular cytokines at the single-cell level by flow
      cytometry has recently become a potent tool in many areas of cell biology and in
      defining the role of cytokines in various human diseases. Three-color flow
      cytometry for detection of intracellular cytokines combined with simultaneous
      determination of lymphocytes (CD3(+) and CD4(+)) or monocytes (CD33(+) and
      CD14(+)) was used for comparison of phytohemagglutinin (PHA)-and phorbol
      myristate acetate (PMA)-ionomycin-induced production of intracellular cytokines
      in peripheral blood mononuclear cells (PBMCs) of healthy donors. We found that
      the number of PBMCs stained for tumor necrosis factor alpha and gamma interferon
      after 6 h of activation was higher when PMA-ionomycin was used for stimulation,
      while the frequencies of cells positive for interleukin 4 (IL-4) were similar for
      both stimulators. However, PMA-ionomycin stimulation caused prominent alterations
      of cell morphology and membrane expression of CD4 and CD14. In contrast, PHA did
      not cause downregulation of surface markers and resulted in less pronounced
      alterations in both forward and side scatter signals during flow cytometry
      analysis. Moreover, during 48 h of culture PHA stimulated tumor necrosis factor
      beta and IL-10 production, which was not observed when PMA-ionomycin was used. We
      conclude that the use of PHA for cell activation may limit in vitro artifacts and
      allow more precise analysis of intracellular cytokine production in various
      disease states.

PMID- 11238214
TI  - Antibody responses to Campylobacter infections determined by an enzyme-linked
      immunosorbent assay: 2-year follow-up study of 210 patients.
AB  - An enzyme-linked immunosorbent assay (ELISA) was adapted to measure
      immunoglobulin G (IgG), IgM, and IgA classes of human serum antibody to
      Campylobacter jejuni and Campylobacter coli. Heat-stable antigen, a combination
      of C. jejuni serotype O:1,44 and O:53 in the ratio 1:1, was used as a coating
      antigen in the ELISA test. A total of 631 sera from 210 patients with verified
      Campylobacter enteritis were examined at various intervals after infection, and a
      control group of 164 sera were tested to determine the cut-off for negative
      results. With a 90th percentile of specificity, IgG, IgM, and IgA showed a
      sensitivity of 71, 60, and 80%, respectively. By combining all three antibody
      classes, the sensitivity was 92% within 35 days after infection, whereas within
      90 days after infection, a combined sensitivity of 90% was found (IgG 68%, IgM
      52%, and IgA 76%). At follow-up of the patients, IgG antibodies were elevated 4.5
      months after infection but exhibited a large degree of variation in antibody
      decay profiles. IgA and IgM antibodies were elevated during the acute phase of
      infection (up to 2 months from onset of infection). The antibody response did not
      depend on Campylobacter species or C. jejuni serotype, with the important
      exception of response to C. jejuni O:19, the serotype most frequently associated
      with Guillain-Barre syndrome. All of the patients infected with this serotype had
      higher levels of both IgM (P = 0.006) and IgA (P = 0.06) compared with other C.
      jejuni and C. coli serotypes.

PMID- 11238215
TI  - Association of Lactobacillus spp. with Peyer's patches in mice.
AB  - Sixteen strains of Lactobacillus isolated from humans, mice, and food products
      were screened for their capacity to associate with Peyer's patches in mice. In
      preliminary experiments, in vitro binding to tissue pieces was assessed by
      scanning electron microscopy, and it was demonstrated qualitatively that 5 of the
      16 strains showed some affinity for the Peyer's patches, irrespective of their
      association with the nonlymphoid intestinal tissue. Lactobacillus fermentum KLD
      was selected for further study, since, in addition to its intrinsically high
      adhesion rate, this organism was found to exhibit a preferential binding to the
      follicle-associated epithelium of the Peyer's patches compared with its level of
      binding to the mucus-secreting regions of the small intestine. Quantitative
      assessment of scanning electron micrographs of tissue sections which had been
      incubated with L. fermentum KLD or a nonbinding control strain, Lactobacillus
      delbruckii subsp. bulgaricus, supported these observations, since a marked
      difference in adhesion was noted (P < 0.05). This preferential association of
      strain KLD with the Peyer's patches was also confirmed with radiolabeled
      lactobacilli incubated with intestinal tissue in the in vitro adhesion assay.
      Direct recovery of L. fermentum KLD from washed tissue following oral dosing of
      mice revealed a distinct association (P < 0.05) between this organism and the
      Peyer's patch tissue. In contrast, L. delbruckii subsp. bulgaricus showed
      negligible binding to both tissue types in both in vitro and in vivo adhesion
      assays. It was concluded that L. fermentum KLD bound preferentially to Peyer's
      patches of BALB/c mice.

PMID- 11238216
TI  - Butyric acid-induced T-cell apoptosis is mediated by caspase-8 and -9 activation
      in a Fas-independent manner.
AB  - Our previous study demonstrated that butyric acid, an extracellular metabolite of
      periodontopathic bacteria, induced apoptosis in murine thymocytes, splenic T
      cells, and human Jurkat cells. In this study, we examined whether CD95 ligand
      receptor interaction is involved in butyric acid-induced T-cell apoptosis. Flow
      cytometry analysis indicated that expression of Fas in Jurkat and T cells from
      peripheral blood mononuclear cells was not affected by butyric acid treatment.
      Furthermore, the expression of Fas and FasL protein in Western blotting was not
      affected by butyric acid treatment. Coincubation with blocking anti-Fas
      antibodies prevented Fas-induced apoptosis but not butyric acid-induced
      apoptosis. Anti-FasL antibodies also did not prevent butyric acid-induced
      apoptosis at any dose examined. Although cytotoxic anti-Fas antibody affected
      butyric acid-induced apoptosis, a synergistic effect was not seen. Time-dependent
      activation of caspase-8 and -9 was recognized in butyric acid- as well as Fas
      mediated apoptosis. IETD-CHO and LEHD-CHO, specific inhibitors of caspase-8 and 
      9, respectively, completely blocked Fas-mediated apoptosis and partially
      prevented butyric acid-induced apoptosis. These results suggest that the Fas-FasL
      interaction is not involved in butyric acid-induced apoptosis and that caspase-8
      and -9-dependent apoptosis plays an important role in butyric acid-induced
      apoptosis, as well as Fas-induced apoptosis.

PMID- 11238217
TI  - Ageing is associated with a prolonged fever response in human endotoxemia.
AB  - The purpose of this study was to investigate whether an age-associated impaired
      acute-phase response exists. Nine healthy elderly volunteers (median, 66 years;
      range, 61 to 69 years) and eight young controls (median, 24 years; range, 20 to
      27 years) were given an intravenous bolus of endotoxin (2 ng/kg). The rectal
      temperature was monitored continuously, and blood samples for cytokine
      measurements were obtained before endotoxin administration as well as 0.5, 1,
      1.5, 2, 3, 4, 8, 12, and 24 h after the injection. The elderly subjects showed a
      more prolonged fever response compared to the young controls. Levels of tumor
      necrosis factor alpha (TNF-alpha), soluble TNF receptors (sTNFR-I), interleukin-6
      (IL-6), IL-8, IL-10, and IL-1 receptor antagonist (IL-1ra) in plasma increased
      markedly following endotoxin administration in both groups. The elderly group
      showed larger initial increases in TNF-alpha and sTNFR-I levels and prolonged
      increased levels of sTNFR-I. Monocyte concentrations decreased in both groups,
      with the elderly group showing a more rapid decrease and a slower subsequent
      increase than did the young group. Furthermore, the elderly group had a more
      rapid increase in C-reactive protein levels than did the young group. In
      conclusion, ageing is associated with an altered acute-phase response including
      initial hyperreactivity, prolonged inflammatory activity, and prolonged fever
      response.

PMID- 11238218
TI  - Cell-mediated immune response to tuberculosis antigens: comparison of skin
      testing and measurement of in vitro gamma interferon production in whole-blood
      culture.
AB  - Although delayed-type hypersensitivity skin testing with tuberculin purified
      protein derivative (PPD) is the standard for tuberculosis screening, its
      variability suggests the need for a more sensitive, noninvasive test. An in vitro
      whole-blood assay has been proposed as an alternative. Using health care worker
      volunteers, we confirmed the correlation between PPD skin test (PPD-ST) results
      (positive, induration of >15 mm) and a standardized gamma interferon (IFN-gamma)
      assay, QuantiFERON-TB (Q-IFN), manufactured by CSL Biosciences in Australia, and
      we evaluated Mycobacterium tuberculosis culture subfractions as potential
      substitutes for PPD. Twenty healthy volunteers with positive PPD-ST results and
      20 PPD-ST-negative controls were enrolled. Whole blood was cultured with human
      PPD antigens (HuPPD), Mycobacterium avium complex (MAC) PPD, phytohemagglutinin
      (PHA), and four M. tuberculosis culture subfractions: low-molecular-weight
      culture, filtrate, culture filtrate without lipoarabinomannan, soluble cell wall
      proteins, and cytosolic proteins, all developed from M. tuberculosis strain
      H(37)RV. Secretion of IFN-gamma (expressed as international units per milliliter)
      was measured by an enzyme immunoassay. The PPD or subculture fraction response as
      a percentage of the PHA response was used to determine positivity. Sixteen of 20
      PPD-ST-positive individuals were classified as M. tuberculosis positive by Q-IFN,
      and 1 was classified as MAC positive. Sixteen of 20 PPD-ST-negative individuals
      were M. tuberculosis negative by Q-IFN, 2 were MAC positive, and 2 were M.
      tuberculosis positive. The tuberculosis culture subfractions stimulated IFN-gamma
      production in PPD-ST-positive volunteers, and significant differences could be
      seen between the two PPD-ST groups with all subfractions except soluble cell wall
      protein; however, the response was variable and no better than the Q-IFN PPD. The
      agreement between the Q-IFN test and the PPD-ST was good (Cohen's kappa = 0.73).
      The Q-IFN assay can be a useful tool in further studies of immune responses to M.
      tuberculosis antigens.

PMID- 11238219
TI  - Validation of a modified commercial enzyme-linked immunoassay for detection of
      human immunodeficiency virus type 1 immunoglobulin G antibodies in saliva.
AB  - This study was performed to evaluate the performance of a saliva collection
      device (OmniSal) and an enzyme-linked immunoassay (EIA) designed for use on serum
      samples (Detect HIV1/2) to detect human immunodeficiency virus type 1 (HIV-1)
      antibodies in the saliva of high-risk women in Mombasa, Kenya. The results of the
      saliva assay were compared to a "gold standard" of a double-EIA testing algorithm
      performed on serum. Individuals were considered HIV-1 seropositive if their serum
      tested positive for antibodies to HIV-1 by two different EIAs. The commercial
      serum-based EIA was modified to test the saliva samples by altering the dilution
      and lowering the cutoff point of the assay. Using the saliva sample, the EIA
      correctly identified 102 of the 103 seropositive individuals, yielding a
      sensitivity of 99% (95% confidence interval [CI], 94 to 100%), and 96 of the 96
      seronegative individuals, yielding a specificity of 100% (95% CI, 95 to 100%). In
      this high-risk population, the positive predictive value of the assay was 100%
      and the negative predictive value was 99%. We conclude that HIV-1 antibody
      testing of saliva samples collected with this device and tested by this EIA is of
      sufficient sensitivity and specificity to make this protocol useful in
      epidemiological studies.

PMID- 11238220
TI  - Two methods for rapid serological diagnosis of acute leptospirosis.
AB  - Leptospirosis is a common and underdiagnosed zoonosis. Two rapid assays for
      serological diagnosis of acute leptospirosis in diagnostic laboratories, the
      immunoglobulin M (IgM)-dipstick assay and the indirect hemagglutination assay
      (IHA), were evaluated and compared with standard assays. Sera were examined from
      104 patients admitted to a hospital for investigation in a leptospirosis
      diagnostic protocol. Specimens for serology were taken on days 1 and 4 of the
      patients' hospital stay. Antibodies were detected using an IgM-enzyme-linked
      immunosorbent assay (ELISA), microscopic agglutination test (MAT), an IgM
      dipstick assay, and an IHA. Fifty-one patients were found to have leptospirosis.
      The sensitivity of the IgM-dipstick assay was 98%, its specificity was 90.6%, its
      positive predictive value was 90.9%, and its negative predictive value was 98%.
      The sensitivity of the IHA was 92.2%, its specificity was 94.4%, its positive
      predictive value was 95.9%, and its negative predictive value was 92.7%. The
      standard IgM-ELISA and MAT, were positive in the first samples tested from 67 and
      55% of the cases, respectively, and the rapid IgM-dipstick assay and IHA were
      positive in 71 and 49%, respectively, in the first sample tested. Both rapid
      assays are highly sensitive and specific. Neither requires specialized equipment,
      and both are suitable for use in diagnostic laboratories.

PMID- 11238221
TI  - Simple and rapid method for production of whole-virus antigen for serodiagnosis
      of caprine arthritis-encephalitis virus by enzyme-linked immunosorbent assay.
AB  - Polyethylene glycol (PEG) was used to produce whole-virus antigen derived from
      tissue culture cells infected with a Canadian strain of caprine arthritis
      encephalitis virus. PEG antigen batches were obtained after precipitation and
      concentration of infected tissue culture material with PEG 8000 and final
      treatment with sodium dodecyl sulfate. The optimum time of harvest of tissue
      culture extracted material to produce the maximum amount of viral proteins was
      determined in roller bottles, after cocultivation of infected and noninfected
      fetal lamb corneal cells. Samples from day 9 to day 25 postculture were collected
      and processed. By Western blotting, the optimum time of harvest was found to be
      day 25 following the coculture. Two large batches of PEG antigen were prepared at
      the optimum time of harvest. Both batches gave similar results when tested by
      Western blotting and enzyme-linked immunosorbent assay (ELISA), using reference
      control sera from infected and noninfected goats. For further testing in ELISA,
      cutoff values and ratios were determined for PEG batch 1, using 200 known serum
      samples from goats free of the disease. The PEG antigen batch was compared with
      an in-house ELISA antigen in a kinetic mode, using 498 serum samples from field
      goats. The in-house ELISA antigen was produced following two rounds of
      ultracentrifugation and treatment with sodium dodecyl sulfate (R. A. Heckert, W.
      B. McNab, S. M. Richardson, and M. R. Briscoe, Can. J. Vet. Res. 56:237-241,
      1992). The PEG antigen batch was found suitable for ELISA, with a relative
      specificity of 100% and a relative sensitivity of 99.4% compared to the in-house
      ELISA antigen. This method of antigen production for ELISA was found to be rapid,
      inexpensive, and reliable for the diagnosis of caprine-arthritis encephalitis,
      without requiring the use of sophisticated laboratory equipment.

PMID- 11238222
TI  - Infectivity-neutralizing and hemagglutinin-inhibiting antibody responses to
      respiratory coronavirus infections of cattle in pathogenesis of shipping fever
      pneumonia.
AB  - Respiratory bovine coronaviruses (RBCV) emerged as an infectious agent most
      frequently isolated from respiratory tract samples of cattle with acute
      respiratory tract diseases. Infectivity-neutralizing (IN) and hemagglutinin
      inhibiting (HAI) antibodies induced by RBCV infections were monitored in
      sequential serum samples collected from cattle during a naturally evolving and
      experimentally monitored epizootic of shipping fever pneumonia (SFP). Cattle
      nasally shedding RBCV at the beginning of the epizootic started with low levels
      of serum IN and HAI antibodies. An increase in serum IN antibody after day 7 led
      to reduction of virus shedding in nasal secretions by the majority of the cattle
      between days 7 and 14. A substantial rise in the serum HAI antibody was observed
      during the initial phase among the sick but not the clinically normal cattle
      which were infected with RBCV. The RBCV isolation-positive cattle that developed
      fatal SFP had minimal serum IN and HAI antibodies during the course of disease
      development. Cattle that remained negative in RBCV isolation tests entered this
      epizootic with high levels of serum IN and HAI antibodies, which dramatically
      increased during the next two weeks. Protection against SFP was apparently
      associated with significantly higher levels of serum IN antibodies at the
      beginning of the epizootic. The RBCV-neutralizing activity is associated with
      serum immunoglobulin G (IgG), particularly the IgG2 subclass, while RBCV-specific
      HAI antibody is related to both serum IgG and IgM fractions.

PMID- 11238223
TI  - Are the opsonophagocytic activities of antibodies in infant sera measured by
      different pneumococcal phagocytosis assays comparable?
AB  - Host protection against Streptococcus pneumoniae is mainly mediated by opsonin
      dependent phagocytosis. Several techniques for measuring opsonophagocytic
      activity (OPA) of antibodies to S. pneumoniae have been standardized and used.
      These include the viable cell-assay, flow-cytometric assays, and an assay
      utilizing radiolabeled bacteria. Using these different methods, we measured the
      OPA of antibodies to S. pneumoniae types 6B and 19F from the sera of infants
      immunized with a pneumococcal conjugate vaccine, PncCRM. Generally, the results
      obtained by the various techniques correlated well, although serotype-specific
      differences were found (6B, r = 0.78 to 0.95, P < 0.001; 19F, r = 0.50 to 0.84, P
      < 0.001). The same serotype-specific differences were observed for the
      relationship between the concentrations of specific immunoglobulin G antibodies
      measured by enzyme immunoassay and the OPA. Since the sensitivities of the OPA
      assays differed, the most prominent discrepancies between the techniques were
      found at low antibody concentrations.

PMID- 11238224
TI  - Rhesus monkey (Macaca mulatta) mucosal antimicrobial peptides are close
      homologues of human molecules.
AB  - One component of host defense at mucosal surfaces appears to be epithelium
      derived antimicrobial peptides. Molecules of the defensin and cathelicidin
      families have been studied in several species, including human and mouse. We
      describe in this report the identification and characterization of rhesus monkey
      homologues of human mucosal antimicrobial peptides. Using reverse transcriptase
      PCR methodology, we cloned the cDNAs of rhesus monkey beta-defensin 1 and 2 (rhBD
      1 and rhBD-2) and rhesus monkey LL-37/CAP-18 (rhLL-37/rhCAP-18). The predicted
      amino acid sequences showed a high degree of homology to the human molecules. The
      expression of the monkey antimicrobial peptides was analyzed using
      immunohistochemistry with three polyclonal antibodies to the human molecules. As
      in humans, rhesus monkey antimicrobial peptides are expressed in epithelia of
      various organs. The present study demonstrates that beta-defensins and
      cathelicidins of rhesus monkeys are close homologues to the human molecules and
      indicate that nonhuman primates represent valid model organisms to study innate
      immune functions.

PMID- 11238225
TI  - Specificities and sensitivities of four monoclonal antibodies for typing of
      Borrelia burgdorferi sensu lato isolates.
AB  - Borrelia burgdorferi, the agent of Lyme borreliosis, is genetically more
      heterogeneous than previously thought. In Europe five genospecies have been
      described from the original B. burgdorferi sensu lato (sl): B. burgdorferi sensu
      stricto (ss), B. garinii, B. afzelii, B. lusitaniae, and B. valaisiana. In the
      United States, B. burgdorferi ss as well as B. bissettii in California and B.
      andersonii on the East Coast were differentiated. In Asia, B. japonica has been
      identified along, with B. garinii, B. afzelii, and B. valaisiana. In order to
      evaluate sensitivity and specificity of four species-specific monoclonal
      antibodies, we analyzed 210 B. burgdorferi sl isolates belonging to eight
      genospecies by immunoblot and confirmed genospecies by restriction fragment
      length polymorphism (RFLP) of rrf (5S)-rrl (23S) intergenic spacer amplicon.
      Monoclonal antibody H3TS had 100% sensitivity for 55 B. burgdorferi ss isolates
      but showed reactivity with all four isolates belonging to B. bissetii. Monoclonal
      antibody I 17.3 showed 100% specificity and sensitivity for 45 B. afzelii
      isolates. Monoclonal antibody D6 was 100% specific for B. garinii but missed 1 of
      64 isolates (98.5% sensitivity). Monoclonal antibody A116k was 100% specific for
      B. valaisiana but was unreactive with 4 of 24 isolates (83.5% sensitivity).
      Genetic analysis correlated well with results of reactivity and confirmed
      efficacy of the phenotypic typing of these antibodies. Some isolates showed
      atypical RFLP. Therefore, both phenotypic and genotypic analyses are needed to
      characterize new Borrelia isolates.

PMID- 11238226
TI  - Field validation of the use of RB51 as antigen in a complement fixation test to
      identify calves vaccinated with Brucella abortus RB51.
AB  - In order to confirm the efficiency of an experimental RB51-based complement
      fixation (CF) test in identifying cattle vaccinated with Brucella abortus strain
      RB51, 831 sera from 110 vaccinated and 48 unvaccinated Hereford heifers of Iowa,
      collected for studies conducted in different years, were sent to Italy without
      coding to be tested in a CF test using RB51 as antigen. Most of the calves, aged
      from 3 to 10 months, were vaccinated subcutaneously with the recommended dosage
      of 10(10) CFU of RB51 commercial vaccine, while only six calves received 10(9)
      CFU of the same vaccine. Serum samples for serologic testing, collected until 16
      postinoculation weeks (PIW), were also tested by routine surveillance tests for
      brucellosis such as rose bengal plate and CF tests performed with B. abortus
      smooth strain 99 as control antigen. RB51 CF test results obtained by testing
      sera from cattle vaccinated in 1999 indicate that the sensitivity of the reaction
      is 97% at 2 to 3 PIW and 90% until 8 PIW and decreases to 65% at 12 PIW, the
      specificity remaining at 100%. Collectively, the results of this study confirm
      that serologic standard tests fail to detect antibodies to RB51 while the RB51
      based CF test is able to monitor antibody responses to RB51 until 15 to 16 PIW
      with a specificity of 100%. In addition, unlike the RB51-based dot blot assay,
      which is the only test currently used to monitor antibody responses to RB51, the
      CF test also detected specific responses following vaccination with 10(9) CFU of
      RB51, although seroconversion was only 50% at 8 PIW. In conclusion, because of
      high specificity and sensitivity, the CF test described here can be used to
      efficaciously monitor serologic responses following RB51 vaccination in cattle
      and could also be employed to detect RB51 infection in humans exposed to this
      strain.

PMID- 11238227
TI  - Antibody responses to MAP 1B and other Cowdria ruminantium antigens are down
      regulated in cattle challenged with tick-transmitted heartwater.
AB  - Serological diagnosis of heartwater or Cowdria ruminantium infection has been
      hampered by severe cross-reactions with antibody responses to related ehrlichial
      agents. A MAP 1B indirect enzyme-linked immunosorbent assay that has an improved
      specificity and sensitivity for detection of immunoglobulin G (IgG) antibodies
      has been developed to overcome this constraint (A. H. M. van Vliet, B. A. M. Van
      der Zeijst, E. Camus, S. M. Mahan, D. Martinez, and F. Jongejan, J. Clin.
      Microbiol. 33:2405-2410, 1995). When sera were tested from cattle in areas of
      endemic heartwater infection in Zimbabwe, only 33% of the samples tested positive
      in this assay despite a high infection pressure (S. M. Mahan, S. M. Samu, T. F.
      Peter, and F. Jongejan, Ann. N.Y. Acad. Sci 849:85-87, 1998). To determine
      underlying causes for this observation, the kinetics of MAP 1B-specific IgG
      antibodies in cattle after tick-transmitted C. ruminantium infection and
      following recovery were investigated. Sera collected weekly over a period of 52
      weeks from 37 cattle, which were naturally or experimentally infected with C.
      ruminantium via Amblyomma hebraeum ticks, were analyzed. MAP 1B-specific IgG
      antibody responses developed with similar kinetics in both field- and laboratory
      infected cattle. IgG levels peaked at 4 to 9 weeks after tick infestation and
      declined to baseline levels between 14 and 33 weeks, despite repeated exposure to
      infected ticks and the establishment of a carrier state as demonstrated by PCR
      and xenodiagnosis. Some of the serum samples from laboratory, and field-infected
      cattle were also analyzed by immunoblotting and an indirect fluorescent-antibody
      test (IFAT) to determine whether this observed seroreversion was specific to the
      MAP 1B antigen. Reciprocal IFAT and immunoblot MAP 1-specific antibody titres
      peaked at 5 to 9 weeks after tick infestation but also declined between 30 and 45
      weeks. This suggests that MAP 1B-specific IgG antibody responses and antibody
      responses to other C. ruminantium antigens are down regulated in cattle despite
      repeated exposure to C. ruminantium via ticks. Significantly, serological
      responses to the MAP 1B antigen may not be a reliable indicator of C. ruminantium
      exposure in cattle in areas of endemic heartwater infection.

PMID- 11238228
TI  - Use of formalin-fixed, propidium iodide-stained human leukocytes as a standard
      for enumerating CD4+ T lymphocytes in a single-platform assay.
AB  - A new, inexpensive method is described that enables lymphocytes to be enumerated
      very precisely. Normal leukocytes were simultaneously stained and fixed with a
      propidium iodide-paraformaldehyde solution. The preparation obtained (CellBeads)
      was used as an internal standard for cell enumeration by flow cytometry and was
      stable at 4 degrees C for at least 60 days. Unlike synthetic beads, the CellBeads
      behaved similarly to normal cells during red blood cell lysis and cell washing
      procedures. When known numbers of CellBeads were added to whole-blood samples and
      the numbers of CellBeads and lymphocytes were determined, highly reproducible and
      accurate enumerations were obtained-far more so than when synthetic beads were
      used. This inexpensive method is suitable for routine use.

PMID- 11238229
TI  - N-formyl-methionyl-leucyl-phenylalanine inhibits both gamma interferon- and
      interleukin-10-induced expression of FcgammaRI on human monocytes.
AB  - Three different classes of receptors for the Fc portion of immunoglobulin G
      (FcgammaRs), FcgammaRI, FcgammaRII, and FcgammaRIII, have been identified on
      human leukocytes. One of them, FcgammaRI, is a high-affinity receptor capable of
      induction of functions that include phagocytosis, respiratory burst, antibody
      dependent cell-mediated cytotoxicity (ADCC), and secretion of cytokines. This
      receptor is expressed on mononuclear phagocytes, and this expression is regulated
      by cytokines and hormones such as gamma interferon (IFN-gamma), IFN-beta,
      interleukin-10 (IL-10), and glucocorticoids. We have recently demonstrated that
      the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) is capable
      of inducing a time-dependent downregulation of both FcgammaRIIIB and FcgammaRII
      in human neutrophils, altering FcgammaR-dependent functions. Considering the
      biological relevance of the regulation of FcgammaRI, we investigated the effect
      of FMLP on the overexpression of FcgammaRI induced by both IFN-gamma and IL-10 on
      human monocytes. We demonstrate that FMLP significantly abrogated IFN-gamma- and
      IL-10-induced FcgammaRI expression, although its basal level of expression was
      not altered. However, other IFN-gamma-mediated effects such as the overexpression
      of the major histocompatibility complex class II antigens and the enhancement of
      lipopolysaccharide-induced secretion of tumor necrosis factor alpha were not
      affected by FMLP treatment. The formyl peptide completely inhibited the IFN-gamma
      and IL-10-induced enhancement of ADCC and phagocytosis carried out by adherent
      cells. The inhibitory effect of FMLP on FcgammaRI upregulation could exert an
      important regulatory effect during the evolution of bacterial infections.

PMID- 11238230
TI  - Early diagnosis of scrub typhus with a rapid flow assay using recombinant major
      outer membrane protein antigen (r56) of Orientia tsutsugamushi.
AB  - The variable 56-kDa major outer membrane protein of Orientia tsutsugamushi is the
      immunodominant antigen in human scrub typhus infections. We developed a rapid
      immunochromatographic flow assay (RFA) for the detection of immunoglobulin M
      (IgM) and IgG antibodies to O. tsutsugamushi. The RFA employs a truncated
      recombinant 56-kDa protein from the Karp strain as the antigen. The performance
      of the RFA was evaluated with a panel of 321 sera (serial bleedings of 85
      individuals suspected of scrub typhus) which were collected in the Pescadore
      Islands, Taiwan, from 1976 to 1977. Among these 85 individuals, IgM tests were
      negative for 7 cases by both RFA and indirect fluorescence assay (IFA) using Karp
      whole-cell antigen. In 29 cases specific responses were detected by the RFA
      earlier than by IFA, 44 cases had the same detection time, and 5 cases were
      detected earlier by IFA than by RFA. For IgG responses, 4 individuals were
      negative with both methods, 37 cases exhibited earlier detection by RFA than IFA,
      42 cases were detected at the same time, and 2 cases were detected earlier by IFA
      than by RFA. The sensitivities of RFA detection of antibody in sera from
      confirmed cases were 74 and 86% for IgM and IgG, respectively. When IgM and IgG
      results were combined, the sensitivity was 89%. A panel of 78 individual sera
      collected from patients with no evidence of scrub typhus was used to evaluate the
      specificity of the RFA. The specificities of the RFA were 99% for IgM and 97% for
      IgG. The sensitivities of IFA were 53 and 73% for IgM and IgG, respectively, and
      were 78% when the results of IgM and IgG were combined. The RFA test was
      significantly better than the IFA test for the early detection of antibody to
      scrub typhus in primary infections, while both tests were equally sensitive with
      reinfected individuals.

PMID- 11238231
TI  - Enzyme immunoassay detection of antigen-specific immunoglobulin g antibodies in
      longitudinal serum samples from patients with cryptosporidiosis.
AB  - Cryptosporidium parvum is a protozoan parasite that causes diarrheal illness in a
      wide range of mammalian hosts, including humans. Characteristic serum
      immunoglobulin G (IgG) antibody responses to antigens in the 27- and 17-kDa size
      ranges have been shown to develop after infection, and several enzyme-linked
      immunosorbent assay (ELISA) and Western blot assay formats have been used to
      measure these IgG levels in human serum. Using a collection of serial samples
      from laboratory-confirmed cryptosporidiosis patients, we compared the results
      obtained by using two new ELISAs with those obtained with two different Western
      blot assays. When assayed with the large-format Western blot, 97% of the 67
      patients had a demonstrable antibody response on at least one occasion. The Cp23
      ELISA correctly identified 93% of the samples that had a 27-kDa response by
      Western blot and 100% of the negative samples. The Triton antigen ELISA detected
      77% of the samples that had a 17-kDa response by Western blot and 88% of the
      negative samples. The sensitivity of the Triton antigen assay was higher for
      samples collected between 16 and 92 days after the onset of symptoms (96%). The
      minigel-format Western blot did not compare favorably with the large-format blot
      for the detection of antibodies to the 27-kDa antigen (71% sensitivity). A half
      life of about 12 weeks was estimated for antibodies to both the 27- and 17-kDa
      antigens. We believe the Cp23 and Triton antigen ELISAs will be useful in
      epidemiologic studies of the prevalence of Cryptosporidium infection in the
      population.

PMID- 11238232
TI  - Dose-dependent circulating immunoglobulin A antibody-secreting cell and serum
      antibody responses in Swedish volunteers to an oral inactivated enterotoxigenic
      Escherichia coli vaccine.
AB  - The immunogenicity of different preparations of an oral inactivated
      enterotoxigenic Escherichia coli (ETEC) vaccine was evaluated in Swedish
      volunteers previously unexposed to ETEC infection. The vaccine preparations
      consisted of recombinant cholera toxin B subunit (CTB) and various amounts of
      formalin-killed whole bacteria expressing the most prevalent colonization factor
      antigens (CFAs). Significant immunoglobulin A (IgA) antibody-secreting cell (ASC)
      responses against CTB and the various CFA components were seen in a majority of
      volunteers after two doses of ETEC vaccine independent of the vaccine lot given.
      The IgA ASC responses against CTB were significantly higher after the second than
      after the first immunization, whereas the CFA-specific IgA ASC responses were
      almost comparable after the first and second doses of ETEC vaccine. Two
      immunizations with one-third of a full dose of CFA-ETEC bacteria induced lower
      frequencies of IgA ASC responses against all the different CFAs than two full
      vaccine doses, i.e., 63 versus 80% for CFA/I, 56 versus 70% for CS1, 31 versus
      65% for CS2, and 56 versus 75% for CS4. The proportion of vaccinees responding
      with rises in the titer of serum IgA antibody against the various CFA antigens
      was also lower after immunization with the reduced dose of CFA-ETEC bacteria.
      These findings suggest that measurements of circulating IgA ASCs can be used not
      only for qualitative but also for quantitative assessments of the immunogenicity
      of individual fimbrial antigens in various preparations of ETEC vaccine.

PMID- 11238233
TI  - Multicenter evaluation of a rapid and convenient method for determination of
      cytomegalovirus immunoglobulin G avidity.
AB  - An easy, rapid, and reproducible test to distinguish residual cytomegalovirus
      (CMV) immunoglobulin M (IgM) antibodies from antibodies produced in primary
      infection could be useful, especially for pregnant women. The CMV avidity of IgG
      antibodies with the VIDAS automated enzyme-linked fluorescent assay and 6 M urea
      was evaluated in a multicenter study to differentiate between primary CMV
      infections and past infections or reactivations. A total of 416 serum specimens
      were tested: 159 specimens were from follow-up of primary infections, and 257
      were from past infections. All of the specimens from primary infections collected
      within 4 months (17 weeks) after the onset of the infection had an avidity index
      lower than 0.8. An avidity index higher than 0.8 excludes a recent primary
      infection of less than 4 months. However, an avidity index higher than 0.8 cannot
      confirm all past infections, since 48 specimens (18%) from past infections had an
      avidity index lower than 0.8 (between 0.5 and 0.8). The exclusion capacity could
      be improved (96.9%) by using a cutoff of 0.7, but this index would decrease the
      specificity of the technique, since the avidity index was found to be between 0.7
      and 0.8 in two patients with recent primary infection. All specimens from primary
      infections obtained more than 4 months after the onset of infection had an
      avidity index more than 0.2. In this study, an avidity index less than 0.2
      confirms the presence of a recent primary infection of less than 4 months. The
      VIDAS CMV IgG avidity test is a rapid, reproducible test with very good
      performance.

PMID- 11238234
TI  - Duration of sample storage dramatically alters expression of the human
      immunodeficiency virus coreceptors CXCR4 and CCR5.
AB  - Expression of the chemokine receptors CXCR4 and CCR5 was monitored using EDTA
      anticoagulated whole blood held for different time periods prior to fluorescent
      antibody staining. When left overnight CXCR4 expression on leukocytes was
      substantially increased, whereas CCR5 expression was reduced. The results were
      similar when heparin and acid-citrate-dextrose were used as anticoagulants.

PMID- 11238235
TI  - Development of a novel screen for protease inhibitors.
AB  - We have developed a novel plasmid-based, quantitative, in vitro screen to test
      the protease-inhibiting activities of existing and newly discovered agents.

PMID- 11238236
TI  - Human T-cell responses to the glucosyltransferases of Streptococcus mutans.
AB  - We previously reported differential humoral responses to glucosyltransferases
      (GTFs), with significantly higher saliva and serum antibody levels to GtfD than
      to GtfB or GtfC. To test the hypothesis that cellular immune responses to these
      molecules also may differ, peripheral blood mononuclear cell (PBMC) and T-cell
      proliferative responses in young adults and children with distinct genetic
      backgrounds were determined using purified recombinant GtfC and GtfD. PBMCs from
      all of the volunteers responded to GtfC and -D, but responses were directed
      predominantly towards GtfD and were major histocompatibility class II antigen
      dependent. A predominant T-cell response to GtfD, over GtfC, was detectable at
      various antigen concentrations ranging from 1 to 20 microg/ml and correlated with
      the differential serum immunoglobulin G (IgG) and salivary IgA antibody responses
      to the GTFs. Therefore, in naturally sensitized humans, Streptococcus mutans GTFs
      stimulate differential humoral and cellular immune responses, with the secreted
      form of GtfD eliciting a stronger response than the cell wall-associated form of
      GtfC.

PMID- 11238237
TI  - Cytokine expression in the mouse brain in response to immune activation by
      Corynebacterium parvum.
AB  - Cytokine expression in the brain has been suggested to mediate various sickness
      behaviors. Here we report that intraperitoneal injection of a Corynebacterium
      parvum antigen in C57BL/6 mice was followed by prolonged upregulation of
      cytokines in the cerebral cortex and subcortical structures in a time course that
      coincided with reduced spontaneous running activity.

PMID- 11238238
TI  - Suppression of endotoxin- and staphylococcal exotoxin-induced cytokines and
      chemokines by a phospholipase C inhibitor in human peripheral blood mononuclear
      cells.
AB  - Excessive release of proinflammatory cytokines from cells stimulated with
      lipopolysaccharide (LPS) or staphylococcal exotoxin (SE) mediates the
      pathophysiologic manifestations of septic shock. Tricyclodecan-9-yl (D609), an
      inhibitor of phosphatidylcholine-specific phospholipase C, suppressed LPS- or SE
      induced cytokines and chemokines in human peripheral blood mononuclear cells.
      These data suggest a potential role for D609 in the treatment of septic shock.

PMID- 11238239
TI  - Detection of serum thermolabile beta-2 macroglycoprotein (Hakata antigen) by
      enzyme-linked immunosorbent assay using polysaccharide produced by Aerococcus
      viridans.
AB  - Although a serum thermolabile beta-2 macroglycoprotein (TMG) may play a role in
      host defense as a lectin, little is known of its related physiological functions,
      mainly due to a lack of appropriate methods for tracing the functions of TMG. We
      identified a polysaccharide from Aerococcus viridans, PSA, which reacts with TMG,
      and based on this finding, we developed an enzyme-linked immunosorbent assay to
      trace the functions of TMG. Using ethanol precipitation and DEAE-Sepharose and
      Sephacryl S-400 column chromatographies, we isolated PSA from cultured medium of
      A. viridans, and it exhibited specific binding against TMG in blood samples. In
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), the
      isolated PSA showed ladder bands that implied the existence of repeating units
      composed of D-glucose, N-acetyl-D-glucosamine, D-mannose, and D-xylose, as
      confirmed by gas chromatography-mass spectrometry. SDS-PAGE and immunochemical
      analysis, using rabbit anti-TMG antibody, showed that PSA specifically binds
      solely to intact serum TMG but not to TMG heated at 56 degrees C for 30 min, a
      condition under which antigenicity is lost. TMG in serum samples bound to PSA in
      a dose-dependent manner, and this binding was clearly suppressed by addition of
      PSA. These observations indicate that PSA is a useful adsorbent to TMG and can be
      used to develop appropriate methods for tracing the functions of TMG.

PMID- 11238240
TI  - Use of Hoechst 33342 staining to detect apoptotic changes in bovine mononuclear
      phagocytes infected with Mycobacterium avium subsp. paratuberculosis.
AB  - Mycobacterium avium subsp. paratuberculosis is an intracellular pathogen of
      macrophages that causes a chronic enteritis (Johne's disease) in ruminants. The
      purpose of this study was to determine whether M. avium subsp. paratuberculosis
      infection causes apoptosis in bovine monocytes. Using Hoechst 33342 staining, we
      observed increased numbers of apoptotic monocytes within 6 h of infection with M.
      avium subsp. paratuberculosis, and these numbers increased further at 24 and 48
      h. This effect appeared to require viable bacilli, because monocytes infected
      with heat-killed M. avium subsp. paratuberculosis did not exhibit a significant
      increase in apoptosis. Preincubation of monocytes with bovine growth hormone
      prior to infection with M. avium subsp. paratuberculosis did not significantly
      alter the number of apoptotic cells.

PMID- 11238241
TI  - Receptor dissociation constants and the information entropy of membranes coding
      ligand concentration.
AB  - The binding of ligands to receptor proteins embedded in cell membranes drives
      cellular responses that involve either second messenger cascades or directly
      gated ion channels. It is known that a single class of receptor proteins
      expresses approximately 98% of its graded response to ligand concentrations over
      four orders of magnitude, where the response is measured by the equilibrium
      proportion of bound ligand-receptor complexes. This four-decadic concentration
      range is centered on a logarithmic scale around logK, where K is the dissociation
      constant defined by the ratio of ligand-receptor unbinding (k-) to binding (k+)
      rates. Remarkably, this four-decadic concentration range is intrinsic to all
      homogeneous ligand-receptor (or, equivalently, enzyme-substrate) systems. Thus,
      adapting the sensitivity of cell membranes to narrower or wider ranges of ligand
      concentrations, respectively, requires multivalent receptors or heterogeneous
      populations of receptors. Here we use a normalized Shannon-Weaver measure of
      information entropy to represent the efficiency of coding over given
      concentrations for membranes containing a population of univalent receptors with
      a specified distribution of dissociation constants, or a homogeneous population
      of strongly cooperative multivalent receptors. Assuming a specified level of
      resolution in the response of cellular or neural systems downstream from the
      membrane that 'read' the ligand concentration 'code', we calculate the range of
      concentrations over which the coding efficiency of the membrane itself is
      maximized. Our results can be used to hypothesize the number of receptor types
      associated with the membranes of particular cells. For example, from data in the
      literature, we conclude that the response of most general olfactory sensory
      neurons can be explained in terms of a homogeneous population of receptor
      proteins, while the response of pheromone sensory neurons is satisfactorily
      explained by the presence of two types of membrane receptor protein with
      pheromone-binding dissociation constants that have values at least one to two
      orders of magnitude apart.

PMID- 11238242
TI  - Reduction of saltiness and bitterness after a chlorhexidine rinse.
AB  - Chronic rinsing with chlorhexidine, an oral-antiseptic, has been shown to
      decrease the saltiness of NaCl and the bitterness of quinine. The effect of acute
      chlorhexidine on taste has not been investigated. The purpose of the present
      study was to examine the effect of acute chlorhexidine rinses on taste intensity
      and quality of 11 stimuli representing sweet, salt, sour, bitter and savory. All
      stimuli were first matched for overall intensity so the effects of chlorhexidine
      would be directly comparable across compounds. As a control treatment, the bitter
      taste of chlorhexidine digluconate (0.12%) was matched in intensity to quinine
      HCl, which was found to cross-adapt the bitterness of chlorhexidine. Subjects
      participated in four experimental conditions: a pre-test, a quinine treatment, a
      chlorhexidine treatment, and a post-test condition, while rating total taste
      intensity and taste qualities in separate test sessions. Relative to the quinine
      treatment, chlorhexidine was found to decrease the salty taste of NaCl, KCl and
      NH4Cl, and not to significantly affect the tastes of sucrose, monosodium
      glutamate (MSG), citric acid, HCl and the taste of water. The bitter taste of
      urea, sucrose octa-acetate and quinine were suppressed after chlorhexidine rinses
      relative to water rinses, but were only marginally suppressed relative to quinine
      rinses. Potential mechanisms are discussed.

PMID- 11238243
TI  - Evidence of odor priming: edibility judgements are primed differently between the
      hemispheres.
AB  - In olfaction, there is only weak evidence of repetition priming. Repetition
      priming was therefore investigated in two experiments using birhinal presentation
      of odors at study and monorhinal at test. Experiment 1 demonstrated repetition
      priming for repeated judgements of edibility in terms of response latency, but
      not in terms of correctness. No differences were found between the hemispheres
      (nostrils). Experiment 2 utilized a slightly different design, in which identity
      of odors was studied and judgement of edibility was tested. This time, only the
      right hemisphere (RH) was associated with priming. This persistence of RH priming
      should be seen in the light of a general tendency for superiority of the left
      hemisphere for correctly judging edibility. It is concluded that the olfactory
      system benefits from previous exposure/processing just as do vision, audition and
      touch. In line with previous research in vision, it is suggested that RH priming
      may be more associated with perceptual priming and left-hemisphere (LH) priming
      with conceptual priming.

PMID- 11238244
TI  - Olfactory perireceptor and receptor events in moths: a kinetic model.
AB  - A mathematical model of perireceptor and receptor events has been developed for
      olfactory sensilla on the antennae of the moth Antheraea polyphemus. The model
      includes the adsorptive uptake of pheromone molecules by the olfactory hair,
      their transport on and within the hair by diffusion, the formation of a complex
      of pheromone and the extracellular pheromone-binding protein (PBP), the
      interaction of the complex pheromone-PBP with the hypothetical receptor molecule
      on the plasma membrane of the olfactory cell, the deactivation of the pheromone
      and, finally, its enzymatic degradation. In the model the PBP with its reduced
      form (with one or two intramolecular disulfide bonds) first acts as a carrier of
      the odorant. Later, while the pheromone is bound, it changes to an oxidized form
      (three disulfide bonds) with a scavenger function (carrier-to-scavenger model).
      This process of pheromone deactivation rather than the enzymatic pheromone
      degradation is responsible for the fall of the receptor potential after stimulus
      offset. The model is based on morphometrical, radiometrical, electrophysiological
      and biochemical data reported by several authors. The study supports the idea
      that peripheral events rather than intracellular signalling processes govern the
      kinetics of the receptor potential in the unadapted receptor cell.

PMID- 11238245
TI  - Updating the str and srj (stl) families of chemoreceptors in Caenorhabditis
      nematodes reveals frequent gene movement within and between chromosomes.
AB  - The seven transmembrane receptor (str) and srj (renamed from stl) families of
      chemoreceptors have been updated and the genes formally named following
      completion of the Caenorhabditis elegans genome sequencing project. Analysis of
      gene locations revealed that 84% of the 320 genes and pseudogenes in these two
      families reside on the large chromosome V. Movements to other chromosomes,
      especially chromosome IV, have nevertheless been relatively common, but only one
      has led to further gene family diversification. Comparisons with homologs in C.
      briggsae indicated that 22.5% of these genes have been newly formed by gene
      duplication since the species split, while also showing that four have been lost
      by large deletions. These patterns of gene evolution are similar to those
      revealed by analysis of the equally large srh family of chemoreceptors, and are
      likely to reflect general features of nematode genome dynamics. Thus large random
      deletions presumably balance the rapid proliferation of genes and their
      degeneration into pseudogenes, while gene movement within and between chromosomes
      keeps these nematode genomes in flux.

PMID- 11238246
TI  - Immunocytochemical study of G(i)2alpha and G(o)alpha on the epithelium surface of
      the rat vomeronasal organ.
AB  - To investigate in detail the distribution of G protein subtypes G(i)2alpha and
      G(o)alpha along the surface of the vomeronasal epithelium, we used double
      labeling immunocytochemical methods and electron microscopy. We examined the
      immunoreactivity of these surface structures with antibodies against G(i)2alpha
      and G(o)alpha. G(i)2alpha- and G(o)alpha-positive cells were observed at the
      epithelial surface and were evenly distributed. Electron microscopy revealed that
      strong immunoreactivities to both antibodies were observed on the microvilli and
      knob-like surface structures of receptor cells. No immunoreactivity was found on
      the microvilli or surface membranes of supporting cells. This expression pattern
      is similar to that reported for putative pheromone receptors. These data confirm
      that there are two distinct classes of vomeronasal receptor cells expressed at
      the surface of the epithelium. These two classes of receptors correspond to the
      same G(i)2alpha- and G(o)alpha-positive cells distributed in cell body layers of
      the epithelium and in the axon terminals in the accessory olfactory bulb.

PMID- 11238247
TI  - Structure-sweetness relationship in thaumatin: importance of lysine residues.
AB  - To clarify the structural basis for the sweetness of thaumatin I, lysine-modified
      derivatives and carboxyl-group-modified derivatives were prepared by chemical
      modification followed by chromatographic purification. The sweetness of
      derivatives was evaluated by sensory analysis. Phosphopyridoxylation of lysine
      residues Lys78, Lys97, Lys106, Lys137 and Lys187 markedly reduced sweetness. The
      intensity of sweetness was returned to that of native thaumatin by
      dephosphorylation of these phosphopyridoxylated lysine residues except Lys106.
      Pyridoxamine modification of the carboxyl group of Asp21, Glu42, Asp60, Asp129 or
      Ala207 (C-terminal) did not markedly change sweetness. Analysis by far-UV
      circular dichroism spectroscopy indicated that the secondary structure of all
      derivatives remained unchanged, suggesting that the loss of sweetness was not a
      result of major disruption in protein structure. The five lysine residues,
      modification of which affected sweetness, are separate and spread over a broad
      surface region on one side of the thaumatin I molecule. These lysine residues
      exist in thaumatin, but not in non-sweet thaumatin-like proteins, suggesting that
      these lysine residues are required for sweetness. These lysine residues may play
      an important role in sweetness through a multipoint interaction with a putative
      thaumatin receptor.

PMID- 11238248
TI  - Immunocytochemistry of glutathione S-transferase in taste bud cells of rat
      circumvallate and foliate papillae.
AB  - Immunocytochemistry was used to investigate the distribution of cells reacting
      with specific antibodies against glutathione S-transferase (GST) mu and pi in rat
      circumvallate and foliate taste buds; the findings were confirmed by Western
      blotting. Double immunofluorescence staining for protein gene product (PGP) 9.5
      and GST subunits allowed the classification of taste bud cells of both papillae
      into: (i) cells immunoreactive to either PGP 9.5 or GST subunit antibody; (ii)
      cells immunoreactive to both antibodies; and (iii) cells that did not react with
      either of these antibodies. Immunoelectron microscopy revealed that most GST
      subunit-immunoreactive cells seemed to be either type II or type III cells based
      on their ultrastructure. Since PGP 9.5 is now widely used as a marker for type
      III cells in mammalian taste buds, it seems reasonable to believe that most GST
      subunit-immunoreactive cells are type II cells. Whether cells immunoreactive for
      both PGP 9.5 and GST subunits constitute a small subpopulation of type III cells
      or whether they are intermediate forms between type II and III cells is under
      investigation. No type I cells reacted with antibodies against GST subunits in
      the present study. GST subunits in taste bud cells may participate in xenobiotic
      metabolism of certain substances exposed to taste pits, as already shown for
      olfactory epithelium.

PMID- 11238251
TI  - The invertebrate odorant-binding protein LUSH is required for normal olfactory
      behavior in Drosophila.
AB  - The invertebrate odorant-binding proteins consist of a large family of low
      molecular-weight, highly divergent proteins expressed exclusively in the
      chemosensory sensilla of insects. Each member of this family studied to date is
      secreted into the sensillum lymph of a small subset of sensilla by non-neuronal
      support cells. These expression patterns suggests an odor-specific function for
      these proteins as opposed to a general role in sensillum biology. Consistent with
      this notion, mutants defective for LUSH, a Drosophila member of this family, have
      odor-specific defects in olfactory behavior. The Drosophila genome contains at
      least 32 members of this gene family, rivaling the number of odorant receptors in
      this species. The relationship between these two protein families and how they
      act to determine odor specificity of olfactory neurons will be the topic of
      future studies.

PMID- 11238252
TI  - Olfaction in Drosophila: coding, genetics and e-genetics.
AB  - Odor coding in Drosophila is examined at both the cellular and molecular levels.
      Functional analysis of individual olfactory receptor neurons (ORNs) by single
      unit electrophysiology has shown that ORNs divide into discrete classes, with
      each class exhibiting a characteristic odor response spectrum. Extensive analysis
      of ORNs in the maxillary palp has revealed six such classes, which are combined
      in sensilla according to a strict pairing rule. In order to identify the odor
      receptor genes that determine the odor specificity of these ORN classes, a new
      algorithm was designed to search DNA databases for proteins with a particular
      structure, as opposed to a particular sequence. The algorithm identified a large
      family of genes likely to encode odor receptors. The acj6 gene, originally
      identified in a screen for mutants defective in olfactory behavior, encodes a
      transcription factor that regulates a subset of these receptor genes, and is
      likely to play a critical role in the process by which ORNs select which
      receptors to express.

PMID- 11238254
TI  - Functional genomics of odor-guided behavior in Drosophila melanogaster.
AB  - The avoidance response to repellent odorants in Drosophila melanogaster, a
      response essential for survival, provides an advantageous model for studies on
      the genetic architecture of olfactory behavior. Transposon tagging in a highly
      inbred strain of flies in combination with a rapid and simple statistical
      behavioral assay enables the identification of not only large phenotypic effects,
      but also small aberrations from wild-type avoidance behavior. The recent
      completion of the sequence of the Drosophila genome facilitates the molecular
      characterization of transposon-tagged genes and correlation between gene
      expression and behavior in smell-impaired (smi) mutant lines. Quantitative
      genetic analyses of a collection of smi lines in a co-isogenic background
      revealed an extensive network of epistatic interactions among genes that shape
      the olfactory avoidance response. Candidate genes for several of these transposon
      tagged smi loci implicate genes that mediate odorant recognition, including a
      novel odorant binding protein; signal propagation, including a voltage-gated
      sodium channel; and a protein containing multiple leucine rich repeats and PDZ
      domains likely to be involved in postsynaptic organization in the olfactory
      pathway. Several novel genes of unknown function have also been implicated,
      including a novel tyrosine-regulated protein kinase. The discovery and
      characterization of novel gene products that have major, hitherto unappreciated
      effects on olfactory behavior will provide new insights in the generation and
      regulation of odor-guided behavior. The identification and functional
      characterization of proteins encoded by smi genes that form part of the olfactory
      subgenome and correlation of polymorphisms in these genes with variation in odor
      guided behavior in natural populations will advance our understanding of the
      genetic architecture of chemosensory behavior.

PMID- 11238253
TI  - The molecular logic of olfaction in Drosophila.
AB  - Drosophila fruit flies display robust olfactory-driven behaviors with an
      olfactory system far simpler than that of vertebrates. Endowed with 1300
      olfactory receptor neurons, these insects are able to recognize and discriminate
      between a large number of distinct odorants. Candidate odorant receptor molecules
      were identified by complimentary approaches of differential cloning and genome
      analysis. The Drosophila odorant receptor (DOR) genes encode a novel family of
      proteins with seven predicted membrane-spanning domains, unrelated to vertebrate
      or nematode chemosensory receptors. There are on the order of 60 or more members
      of this gene family in the Drosophila genome, far fewer than the hundreds to
      thousands of receptors found in vertebrates or nematodes. DOR genes are
      selectively expressed in small subsets of olfactory neurons, in expression
      domains that are spatially conserved between individuals, bilaterally symmetric
      and not sexually dimorphic. Double in situ RNA hybridization with a number of
      pairwise combinations of DOR genes fails to reveal any overlap in gene
      expression, suggesting that each olfactory neuron expresses one or a small number
      of receptor genes and is therefore functionally distinct. How is activation of
      such a subpopulation of olfactory receptor neurons in the periphery sensed by the
      brain? In the mouse, all neurons expressing a given receptor project with
      precision to two of 1800 olfactory bulb glomeruli, creating a spatial map of odor
      quality in the brain. We have employed DOR promoter transgenes that recapitulate
      expression of endogenous receptor to visualize the projections of individual
      populations of receptor neurons to subsets of the 43 glomeruli in the Drosophila
      antennal lobe. The results suggest functional conservation in the logic of
      olfactory discrimination from insects to mammals.

PMID- 11238255
TI  - Foraging behaviour in Drosophila larvae: mushroom body ablation.
AB  - Drosophila larvae and adults exhibit a naturally occurring genetically based
      behavioural polymorphism in locomotor activity while foraging. Larvae of the
      rover morph exhibit longer foraging trails than sitters and forage between food
      patches, while sitters have shorter foraging trails and forage within patches.
      This behaviour is influenced by levels of cGMP-dependent protein kinase (PGK)
      encoded by the foraging (for) gene. Rover larvae have higher expression levels
      and higher PGK activities than do sitters. Here we discuss the importance of the
      for gene for studies of the mechanistic and evolutionary significance of
      individual differences in behaviour. We also show how structure-function analysis
      can be used to investigate a role for mushroom bodies in larval behaviour both in
      the presence and in the absence of food. Hydroxyurea fed to newly hatched larvae
      prevents the development of all post-embryonically derived mushroom body (MB)
      neuropil. This method was used to ablate MBs in rover and sitter genetic variants
      of foraging to test whether these structures mediate expression of the foraging
      behavioural polymorphism. We found that locomotor activity levels during foraging
      of both the rover and sitter larval morphs were not significantly influenced by
      MB ablation. Alternative hypotheses that may explain how variation in foraging
      behaviour is generated are discussed.

PMID- 11238256
TI  - Workshop Executive Summary Report: Post-resuscitative and initial Utility in Life
      Saving Efforts (PULSE): June 29-30, 2000; Lansdowne Resort and Conference Center;
      Leesburg, VA.

PMID- 11238257
TI  - Acceleration of restenosis by diabetes: pathogenetic implications.

PMID- 11238258
TI  - Epidemiological findings imply that goals for drug treatment of hypertension need
      to be revised.

PMID- 11238259
TI  - Rapid reduction in C-reactive protein with cerivastatin among 785 patients with
      primary hypercholesterolemia.
AB  - BACKGROUND: Long-term therapy with hydroxymethylglutaryl coenzyme A reductase
      inhibitors (statins) has been shown to reduce levels of C-reactive protein (CRP).
      However, the generalizability, speed of onset, and dose-response characteristics
      of this effect are uncertain. METHODS AND RESULTS: We measured CRP, LDL
      cholesterol (LDL-C), and HDL cholesterol (HDL-C) levels among 785 patients with
      primary hypercholesterolemia at baseline and after 8 weeks of therapy with either
      0.4 or 0.8 mg of cerivastatin. Overall, cerivastatin resulted in a 13.3%
      reduction in median CRP levels (P:<0.001) and a 24.5% reduction in mean CRP
      levels (P:<0.001). Although LDL-C promptly decreased in a dose-dependent manner
      (mean LDL-C reduction, 37.3% for 0.4 mg and 42.2% for 0.8 mg of cerivastatin), no
      clear dose-response effect of cerivastatin on CRP was observed, nor was there any
      substantive correlation between the magnitude of change in CRP and the magnitude
      of change in LDL-C (r=-0.08) or the magnitude of change in HDL-C (r=-0.04). Thus,
      <2% of the variance in the percent change in CRP over 8 weeks could be attributed
      to the percent change in either of these lipid parameters. Further, there was no
      evidence of correlation between baseline CRP levels and baseline lipid levels or
      between end-of-study CRP levels and end-of-study lipid levels. CONCLUSIONS: Among
      785 patients with primary hypercholesterolemia, CRP levels were significantly
      reduced within 8 weeks of initiating cerivastatin therapy in a lipid-independent
      manner.

PMID- 11238260
TI  - C-reactive protein-mediated low density lipoprotein uptake by macrophages:
      implications for atherosclerosis.
AB  - BACKGROUND: LDL and C-reactive protein (CRP) are important cardiovascular risk
      factors. Both LDL and CRP deposit in the arterial wall during atherogenesis.
      Stranded LDL is taken up by macrophages, causing foam cell formation. Because
      native LDL does not induce foam cell formation, we hypothesized that CRP may
      opsonize native LDL for macrophages. METHODS AND RESULTS: Monocytes were isolated
      from human blood and transformed into macrophages. CRP/LDL uptake was assessed by
      immunofluorescent labeling and the use of confocal laser scanning microscopy.
      Native LDL coincubated with CRP was taken up by macrophages by macropinocytosis.
      Uptake of the CRP/LDL coincubate was mediated by the CRP receptor CD32.
      CONCLUSIONS: We conclude that foam cell formation in human atherogenesis may be
      caused in part by uptake of CRP-opsonized native LDL.

PMID- 11238261
TI  - Common genetic variation in ABCA1 is associated with altered lipoprotein levels
      and a modified risk for coronary artery disease.
AB  - BACKGROUND: Low plasma HDL cholesterol (HDL-C) is associated with an increased
      risk of coronary artery disease (CAD). We recently identified the ATP-binding
      cassette transporter 1 (ABCA1) as the major gene underlying the HDL deficiency
      associated with reduced cholesterol efflux. Mutations within the ABCA1 gene are
      associated with decreased HDL-C, increased triglycerides, and an increased risk
      of CAD. However, the extent to which common variation within this gene influences
      plasma lipid levels and CAD in the general population is unknown. METHODS AND
      RESULTS: We examined the phenotypic effects of single nucleotide polymorphisms in
      the coding region of ABCA1. The R219K variant has a carrier frequency of 46% in
      Europeans. Carriers have a reduced severity of CAD, decreased focal (minimum
      obstruction diameter 1.81+/-0.35 versus 1.73+/-0.35 mm in noncarriers, P:=0.001)
      and diffuse atherosclerosis (mean segment diameter 2.77+/-0.37 versus 2.70+/-0.37
      mm, P:=0.005), and fewer coronary events (50% versus 59%, P:=0.02).
      Atherosclerosis progresses more slowly in carriers of R219K than in noncarriers.
      Carriers have decreased triglyceride levels (1.42+/-0.49 versus 1.84+/-0.77
      mmol/L, P:=0.001) and a trend toward increased HDL-C (0.91+/-0.22 versus 0.88+/
      0.20 mmol/L, P:=0.12). Other single nucleotide polymorphisms in the coding region
      had milder effects on plasma lipids and atherosclerosis. CONCLUSIONS: These data
      suggest that common variation in ABCA1 significantly influences plasma lipid
      levels and the severity of CAD.

PMID- 11238262
TI  - Detection of fibrous cap in atherosclerotic plaque by intravascular ultrasound by
      use of color mapping of angle-dependent echo-intensity variation.
AB  - BACKGROUND: The thickness of the fibrous cap is a major determinant in the
      vulnerability of atherosclerotic plaque to rupture. It has been demonstrated that
      intravascular ultrasound (IVUS) backscatter from fibrous tissue is strongly
      dependent on the ultrasound beam angle of incidence. This study investigated the
      feasibility of using a new IVUS color mapping technique representing the angle
      dependent echo-intensity variation to determine the thickness of the fibrous cap
      in atherosclerotic plaque. METHODS AND RESULTS: Nineteen formalin-fixed
      noncalcified human atherosclerotic plaques from necropsy were imaged in vitro
      with a 30-MHz IVUS catheter. The IVUS catheter was moved coaxially relative to
      the plaque. The images showing maximum and minimum echo intensity of the plaque
      surface were selected to calculate the angle-dependent echo-intensity variation.
      A colorized representation of the echo-intensity variation in the plaque was
      obtained from the 2 IVUS images. A clearly bordered area with large variation in
      echo intensity was revealed for each plaque surface in the colorized IVUS image.
      The thickness (x, mm) of this area correlated significantly with that of fibrous
      cap (y, mm) measured from histologically prepared sections as y=1.05x-0.01
      (r=0.81, P:<0.0001). Bland-Altman analysis also supported the reliability of this
      method (mean difference, 0.00+/-0.10 mm). CONCLUSIONS: This novel technique for
      color mapping the echo-intensity variation in IVUS provided an accurate
      representation of the thickness of the fibrous cap in atherosclerotic plaque.
      This method may be useful in assessing plaque vulnerability to rupture in
      atherosclerosis.

PMID- 11238263
TI  - Intracoronary Doppler- and quantitative coronary angiography-derived predictors
      of major adverse cardiac events after stent implantation.
AB  - BACKGROUND: Distal coronary flow velocity reserve (CVR) is significantly improved
      after a successful balloon angioplasty (PTCA). Furthermore, a postinterventional
      CVR >2.5 and a percent diameter stenosis (%DS) </=35% are predictive for a low
      incidence of major adverse cardiac events (MACE) at 6 months of 16%. Similar
      results are lacking for coronary stenting. METHODS AND RESULTS: In 150 patients,
      baseline and hyperemic coronary flow velocities were recorded with a Doppler
      guidewire distal to the target lesion and in an unobstructed reference artery
      before and after PTCA, after stenting, and at 6 months. Distal CVR and relative
      CVR (CVR(rel)) were calculated. Logistic regression and receiver operating
      characteristic analyses were applied to determine prognostic cutoff values of
      CVR, CVR(rel), %DS, and minimal lumen diameter separately and in combination to
      predict MACE at 6 months. After stenting, CVR (2.96+/-0.87 versus 2.40+/-0.7;
      P:=0.001), CVR(rel) (1.02+/-0.24 versus 0.81+/-0.24; P:=0.001), and minimal lumen
      diameter (2.98+/-0.56 versus 2.11+/-0.74 mm; P:=0.001) were significantly higher
      than after PTCA. Thirty-three patients developed MACE. A postinterventional
      CVR(rel)>0.88 was the best single predictor of MACE, with an incidence of 6.8%,
      whereas the combination of a CVR(rel)>0.88 and a %DS </=11.2% predicted an
      incidence of MACE of 1.5%. CONCLUSIONS: Measurement of CVR(rel) and %DS after
      stent implantation are best suitable to predict MACE at 6 months.

PMID- 11238265
TI  - ABC stenosis morphology classification and outcome of coronary angioplasty:
      reassessment with computing techniques.
AB  - BACKGROUND: The American College of Cardiology/American Heart Association
      (ACC/AHA) stenosis morphology classification (MC) stratifies coronary lesions for
      probability of success and complications after coronary angioplasty (PTCA).
      Modern computing techniques were used to evaluate the individual predictive value
      of MC in random PTCA cases. METHODS AND RESULTS: MC was attributed to the target
      lesions by consensus of 2 observers. The predictive value regarding procedural
      success (PS) and major adverse cardiac events (MACE) of MC was analyzed by
      conventional logistic regression analyses and by inductive machine learning
      models. The study was adequately powered for the methods applied with 325 target
      lesions of 250 cases. Overall, PS decreased and MACE increased from type A to
      type C lesions. Regression analysis identified no single factor as predictive.
      Logistic regression showed an error rate of 42%. Machine learning techniques
      achieved an individual predictive error of only 10%, which could be further
      reduced to 2% by addition of parameters. For PS, MC parameters showed a high
      ranking for building the model. For MACE, variables of the medical history showed
      more impact. CONCLUSIONS: MC per se cannot individually predict PS or MACE.
      However, when all MC parameters are integrated together with additional lesion
      specific and history variables, a high individual predictive value can be
      achieved. This technique may be clinically helpful for risk stratification in the
      catheterization laboratory and improvement of classification systems in
      interventional cardiology.

PMID- 11238264
TI  - Patency of percutaneous transluminal coronary angioplasty sites at 6-month
      angiographic follow-up: A key determinant of survival in diabetics after coronary
      balloon angioplasty.
AB  - BACKGROUND: Several reports have demonstrated a high mortality rate in diabetic
      patients treated by standard coronary balloon angioplasty. No clear explanation
      has been provided for this finding. METHODS AND RESULTS: Consecutive diabetic
      patients successfully treated by standard coronary balloon angioplasty (n=604)
      were enrolled in a follow-up program including repeated angiography at 6 months
      and long-term clinical follow-up. Clinical follow-up was available in 603
      patients (99.8%). Twelve patients died, 2 underwent bypass surgery before
      scheduled repeated angiography, and 76 declined angiography. Determinants of long
      term mortality were analyzed in the 513 patients with angiography at 6 months and
      long-term clinical follow-up (mean follow-up, 6.5+/-2.4 years). On the basis of
      the results of repeated angiography, 3 groups of patients were defined: group 1,
      162 patients without restenosis (32%); group 2, 257 patients with nonocclusive
      restenosis (50%); and group 3, 94 patients with coronary occlusion (18%). Overall
      actuarial 10-year mortality rate was 36%. Actuarial 10-year mortality was 24% in
      group 1, 35% in group 2, and 59% in group 3 (P:<0.0001). Multivariate analysis
      demonstrated that coronary occlusion was a strong and independent correlate of
      long-term total mortality (hazard ratio, 2.16; 95% CI, 1.43 to 3.26; P:=0.0003)
      and cardiac mortality (hazard ratio, 2.38; 95% CI, 1.48 to 3.85; P:=0.0004).
      CONCLUSIONS: This study demonstrates that restenosis, especially in its occlusive
      form, is a major determinant of long-term mortality in diabetic patients after
      coronary balloon angioplasty.

PMID- 11238266
TI  - Deceleration time in ischemic cardiomyopathy: relation to echocardiographic and
      scintigraphic indices of myocardial viability and functional recovery after
      revascularization.
AB  - BACKGROUND: In patients with heart failure secondary to left ventricular (LV)
      systolic dysfunction, a short deceleration time (DT) successfully predicts
      clinical outcome. The impact of myocardial viability and revascularization on the
      mitral inflow velocities, however, is unknown. METHODS AND RESULTS: Forty
      patients with ischemic cardiomyopathy underwent (201)Tl scintigraphy (SPECT) and
      2D, Doppler, and dobutamine echocardiography (DE, to 40 microg. kg(-1). min(-1))
      2 days before CABG. Echocardiography was repeated 3 months after
      revascularization to determine recovery of function. Significant correlations
      were present between DT and LV contractile reserve by DE (r=0.72), scar perfusion
      defect by SPECT (r=-0.69), and the change in ejection fraction (DeltaEF) after
      surgery (r=0.77) (all P:<0.01). DT >150 ms effectively identified (sensitivity
      79%, specificity 81%) patients with DeltaEF >/=5%. The population was divided
      into 2 groups according to DT: group 1 (DT >150 ms, n=21) and group 2 (DT </=150
      ms, n=19). At baseline, NYHA class, LV EF, age, and use of cardiovascular drugs
      were similar between the 2 groups. The number of viable segments by both DE and
      SPECT, however, was higher in group 1 (both P:<0.01), and only patients in group
      1 had an increase in EF (29+/-4.8% to 40+/-8%, P:<0.01) after surgery. Death and
      heart transplantation occurred in 7 patients from group 2 and 1 patient from
      group 1 (P:=0.017). CONCLUSIONS: In patients with ischemic cardiomyopathy, the
      reduced amount of viable myocardium results in a restrictive mitral inflow
      pattern, which in turn predicts poor survival.

PMID- 11238268
TI  - Does the relation of blood pressure to coronary heart disease risk change with
      aging? The Framingham Heart Study.
AB  - BACKGROUND: We examined the relative importance of diastolic (DBP), systolic
      (SBP) and pulse pressure (PP) as predictors of coronary heart disease (CHD) risk
      in different age groups of Framingham Heart Study participants. METHODS AND
      RESULTS: We studied 3060 men and 3479 women between 20 and 79 years of age who
      were free of CHD and were not on antihypertensive drug therapy at baseline. Cox
      regression adjusted for age, sex, and other risk factors was used to assess the
      relations of BP indexes to CHD risk over a 20-year follow-up. In the group <50
      years of age, DBP was the strongest predictor of CHD risk (hazard ratio [HR] per
      10 mm Hg increment, 1.34; 95% CI, 1.18 to 1.51) rather than SBP (HR, 1.14; 95%
      CI, 1.06 to 1.24) or PP (HR, 1.02; 95% CI, 0.89 to 1.17). In the group 50 to 59
      years of age, risks were comparable for all 3 BP indexes. In the older age group,
      the strongest predictor of CHD risk was PP (HR, 1.24; 95% CI, 1.16 to 1.33). When
      both SBP and DBP were considered jointly, the former was directly and the latter
      was inversely related to CHD risk in the oldest age group CONCLUSIONS: With
      increasing age, there was a gradual shift from DBP to SBP and then to PP as
      predictors of CHD risk. In patients <50 years of age, DBP was the strongest
      predictor. Age 50 to 59 years was a transition period when all 3 BP indexes were
      comparable predictors, and from 60 years of age on, DBP was negatively related to
      CHD risk so that PP became superior to SBP.

PMID- 11238267
TI  - Structural alterations in subcutaneous small arteries of normotensive and
      hypertensive patients with non-insulin-dependent diabetes mellitus.
AB  - BACKGROUND: It is not presently known whether non-insulin-dependent diabetes
      mellitus (NIDDM) is associated with the presence of structural alterations in
      small arteries or whether the combination of hypertension and NIDDM may have an
      additive effect on endothelial dysfunction. Therefore, we investigated
      subcutaneous small arteries in 12 normotensive subjects (NT group), 18 patients
      with essential hypertension (EH group), 13 patients with NIDDM, and 11 patients
      with NIDDM and EH (NIDDM+EH group). METHODS AND RESULTS: Subcutaneous small
      arteries were evaluated by a micromyographic technique. The internal diameter,
      the media-to-lumen ratio, remodeling and growth indices, and the collagen-to
      elastin ratio were calculated. Concentration-response curves to acetylcholine,
      bradykinin, the endothelium-independent vasodilator sodium nitroprusside, and
      endothelin-1 were performed. The media-to-lumen ratio was higher in the EH,
      NIDDM, and NIDDM+EH groups compared with the NT group. EH patients showed the
      presence of eutrophic remodeling, whereas NIDDM and NIDDM+EH patients showed 40%
      to 46% cell growth. The collagen-to-elastin ratio was significantly increased in
      the EH and NIDDM+EH groups compared with the NT group. The vasodilatation to
      acetylcholine and bradykinin was similarly reduced in EH, NIDDM, and NIDDM+EH
      groups compared with the NT group. The contractile responses to endothelin-1 were
      similarly reduced in EH, NIDDM, and NIDDM+EH patients. CONCLUSIONS: Our data
      suggest that the effects of NIDDM and EH on small artery morphology are
      quantitatively similar but qualitatively different and that the presence of
      hypertension in diabetic patients has little additive effect on small artery
      morphology and none on endothelial dysfunction.

PMID- 11238269
TI  - Positive and negative feedback mechanisms in the neural regulation of
      cardiovascular function in healthy and spinal cord-injured humans.
AB  - BACKGROUND: We tested the hypothesis that in humans, hypertension/tachycardia and
      hypotension/bradycardia nonbaroreflex sequences that occur within spontaneous
      arterial pressure (AP) and R-R interval fluctuations are an expression of
      positive feedback mechanisms neurally regulating the cardiovascular system.
      METHODS AND RESULTS: We studied 15 spinal cord-injured (SCI) subjects (8
      tetraplegics and 7 paraplegics) and 8 healthy subjects. The occurrence of
      nonbaroreflex (NBseq) and baroreflex (Bseq) sequences, ie, hypertension
      bradycardia and hypotension-tachycardia sequences, was assessed during rest and
      head-up tilt (HUT). The ratio between Bseq and NBseq (B/NB ratio) was also
      calculated. In resting conditions, the occurrence of NBseq was significantly
      lower (P:<0.05) in tetraplegics (7.9+/-1.5) than in paraplegics (16.2+/-3.2) and
      normal subjects (19.0+/-3.5), whereas the occurrence of Bseq was not
      significantly different between the 3 groups (38.6+/-11.9 versus 45.4+/-6.0
      versus 47.0+/-11.9). In tetraplegics, the B/NB ratio showed a marked, significant
      decrease (from 8.4+/-4.2 to 1.9+/-0.8, P:<0.05) in response to HUT, whereas in
      normal subjects, it showed a significant increase (from 3.5+/-0.7 to 9.4+/-2.7,
      P:<0.05). In paraplegics, the B/NB ratio did not change significantly in response
      to HUT (from 4.5+/-1.6 to 4.8+/-1.1). CONCLUSIONS: Our data suggest that
      nonbaroreflex sequences occur in humans and might represent the expression of an
      integrated, neurally mediated, feed-forward type of short-term cardiovascular
      regulation that is able to interact dynamically with feedback mechanisms of
      baroreflex origin.

PMID- 11238270
TI  - Novel gene mutations in patients with left ventricular noncompaction or Barth
      syndrome.
AB  - BACKGROUND: Mutations in the gene G4.5 result in a wide spectrum of severe
      infantile cardiomyopathic phenotypes, including isolated left ventricular
      noncompaction (LVNC), as well as Barth syndrome (BTHS) with dilated
      cardiomyopathy (DCM). The purpose of this study was to investigate patients with
      LVNC or BTHS for mutations in G4.5 or other novel genes. METHODS AND RESULTS: DNA
      was isolated from 2 families and 3 individuals with isolated LVNC or LVNC with
      congenital heart disease (CHD), as well as 4 families with BTHS associated with
      LVNC or DCM, and screened for mutations by single-strand DNA conformation
      polymorphism analysis and DNA sequencing. In 1 family with LVNC and CHD, a C-->T
      mutation was identified at nucleotide 362 of alpha-dystrobrevin, changing a
      proline to leucine (P121L). Mutations in G4.5 were identified in 2 families with
      isolated LVNC: a missense mutation in exon 4 (C118R) in 1 and a splice donor
      mutation (IVS10+2T-->A) in intron 10 in the other. In a family with
      cardiomyopathies ranging from BTHS or fatal infantile cardiomyopathy to
      asymptomatic DCM, a splice acceptor mutation in exon 2 of G4.5 (398-2 A-->G) was
      identified, and a 1-bp deletion in exon 2 of G4.5, resulting in a stop codon
      after amino acid 41, was identified in a sporadic case of BTHS. CONCLUSIONS:
      These data demonstrate genetic heterogeneity in LVNC, with mutation of a novel
      gene, alpha-dystrobrevin, identified in LVNC associated with CHD. In addition,
      these results confirm that mutations in G4.5 result in a wide phenotypic spectrum
      of cardiomyopathies.

PMID- 11238271
TI  - Impact of low birth weight and cardiovascular risk factors on endothelial
      function in early adult life.
AB  - BACKGROUND: Low birth weight is related to increased risk of coronary heart
      disease in adults and recently has been associated with vascular endothelial
      dysfunction in children. We investigated whether the relation between birth
      weight and endothelial function was still present in early adult life and whether
      there was an interaction with emerging risk factors. METHODS AND RESULTS: In 315
      adults (165 women, 150 men, aged 20 to 28 years), high-resolution ultrasound was
      used to determine endothelium-dependent and -independent vascular responses of
      the brachial artery. Vascular measures were related to classic risk factors
      (smoking history, lipid profile, blood pressure, fasting insulin, exercise
      capacity, body mass index, and combined risk score) and birth weight. Low birth
      weight was associated with reduced flow-mediated dilation (coefficient=0.18 kg(
      1), 95% CI 0.004 to 0.35, P:=0.04) but not with endothelium-independent dilation.
      The difference in flow-mediated dilation between the top and bottom fifths of
      birth weight was the same as between smokers and nonsmokers. Increasing levels of
      acquired risk factors overwhelmed the association, and there was a significant
      interaction of risk score with the birth weight-endothelial function relation
      (coefficient of interaction term [birth weightxrisk score] = -0.12, 95% CI -0.22
      to -0.03, P:=0.01). CONCLUSIONS: Low birth weight is associated with endothelial
      dysfunction in young adults. This is most marked in individuals with lower risk
      factor profiles and may be relevant to the pathogenesis of atherosclerosis in
      later life.

PMID- 11238272
TI  - Improved surgical outcome after fetal diagnosis of hypoplastic left heart
      syndrome.
AB  - BACKGROUND: Hypoplastic left heart syndrome (HLHS) is frequently diagnosed
      prenatally, but this has not been shown to improve surgical outcome. METHODS AND
      RESULTS: We reviewed patients with HLHS between July 1992 and March 1999 to
      determine the influence of prenatal diagnosis on preoperative clinical status,
      outcomes of stage 1 surgery, and parental decisions regarding care. Of 88
      patients, 33 were diagnosed prenatally and 55 after birth. Of 33 prenatally
      diagnosed patients, 22 were live-born, and pregnancy was terminated in 11. Of 22
      prenatally diagnosed patients who were live-born, 14 underwent surgery, and
      parents elected to forego treatment in 8. Of 55 patients diagnosed postnatally,
      38 underwent surgery, and 17 did not because of parental decisions or clinical
      considerations. Prenatally diagnosed patients were less likely to undergo surgery
      than patients diagnosed after birth (P:=0.008). Among live-born infants, there
      was a similar rate of nonintervention. Among patients who underwent surgery,
      survival was 75% (39/52). All patients who had a prenatal diagnosis and underwent
      surgery survived, whereas only 25 of 38 postnatally diagnosed patients survived
      (P:=0.009). Patients diagnosed prenatally had a lower incidence of preoperative
      acidosis (P:=0.02), tricuspid regurgitation (P:=0.001), and ventricular
      dysfunction (P:=0.004). They were also less likely to need preoperative inotropic
      medications or bicarbonate (P:=0.005). Preoperative factors correlating with
      early mortality included postnatal diagnosis (P:=0.009), more severe acidosis
      (P:=0.03), need for bicarbonate or inotropes (P:=0.008 and 0.04), and ventricular
      dysfunction (P:=0.05). CONCLUSIONS: Prenatal diagnosis of HLHS was associated
      with improved preoperative clinical status and with improved survival after first
      stage palliation in comparison with patients diagnosed after birth.

PMID- 11238273
TI  - Long-term stable correction of low-density lipoprotein receptor-deficient mice
      with a helper-dependent adenoviral vector expressing the very low-density
      lipoprotein receptor.
AB  - BACKGROUND: Familial hypercholesterolemia (FH) that results from LDL receptor
      (LDLR) deficiency affects approximately 1 in 500 persons in the heterozygous
      state and approximately 1 in 1 million persons in the homozygous state. We tested
      a novel gene therapy strategy for the treatment of FH in a mouse model. METHODS
      AND RESULTS: We delivered the VLDL receptor (VLDLR) to the liver of LDLR
      deficient mice and compared the effect of a helper-dependent adenoviral vector
      with all viral coding sequences deleted (HD-Ad-mVLDLR) with a first-generation
      vector (FG-Ad-mVLDLR), an HD-Ad (HD-Ad-0) that contained no expression cassette,
      and dialysis buffer (DB). A single intravenous injection of HD-Ad-mVLDLR led to a
      lowering of plasma cholesterol that lasted >/=6 months. Acute liver toxicity (as
      measured with liver enzyme elevation) occurred after FG-Ad-mVLDLR but not after
      HD-Ad-mVLDLR, HD-Ad-0, or DB treatment. At 6 months, VLDLR was detected in the
      liver with Western blotting and with immunofluorescence staining only in HD-Ad
      mVLDLR-treated mice. Aortic atherosclerosis was almost completely prevented in
      these animals. CONCLUSIONS: HD-Ad-mediated intravenous delivery of VLDLR to
      hepatocytes is well tolerated. It produces long-term lowering of plasma
      cholesterol and prevents atherosclerosis development in LDLR-deficient mice.
      These data provide support for the feasibility and safety of this approach for
      therapy of human subjects.

PMID- 11238274
TI  - Endothelial regulation of vasomotion in apoE-deficient mice: implications for
      interactions between peroxynitrite and tetrahydrobiopterin.
AB  - BACKGROUND: Altered endothelial cell nitric oxide (NO(*)) production in
      atherosclerosis may be due to a reduction of intracellular tetrahydrobiopterin,
      which is a critical cofactor for NO synthase (NOS). In addition, previous
      literature suggests that inactivation of NO(*) by increased vascular production
      superoxide (O(2)(*-)) also reduces NO(*) bioactivity in several disease states.
      We sought to determine whether these 2 seemingly disparate mechanisms were
      related. METHODS AND RESULTS: Endothelium-dependent vasodilation was abnormal in
      aortas of apoE-deficient (apoE(-/-)) mice, whereas vascular superoxide production
      (assessed by 5 micromol/L lucigenin) was markedly increased. Treatment with
      either liposome-entrapped superoxide dismutase or sepiapterin, a precursor to
      tetrahydrobiopterin, improved endothelium-dependent vasodilation in aortas from
      apoE(-/-) mice. Hydrogen peroxide had no effect on the decay of
      tetrahydrobiopterin, as monitored spectrophotometrically. In contrast, superoxide
      modestly and peroxynitrite strikingly increased the decay of tetrahydrobiopterin
      over 500 seconds. Luminol chemiluminescence, inhibitable by the peroxynitrite
      scavengers ebselen and uric acid, was markedly increased in apoE(-/-) aortic
      rings. In vessels from apoE(-/-) mice, uric acid improved endothelium-dependent
      relaxation while having no effect in vessels from control mice. Treatment of
      normal aortas with exogenous peroxynitrite dramatically increased vascular O(2)(*
      ) production, seemingly from eNOS, because this effect was absent in vessels
      lacking endothelium, was blocked by NOS inhibition, and did not occur in vessels
      from mice lacking eNOS. CONCLUSIONS: Reactive oxygen species may alter
      endothelium-dependent vascular relaxation not only by the interaction of O(2)(*-)
      with NO(*) but also through interactions between peroxynitrite and
      tetrahydrobiopterin. Peroxynitrite oxidation of tetrahydrobiopterin may represent
      a pathogenic cause of "uncoupling" of NO synthase.

PMID- 11238275
TI  - Serotonin-induced hypercontraction through 5-hydroxytryptamine 1B receptors in
      atherosclerotic rabbit coronary arteries.
AB  - BACKGROUND: Augmented vasoconstriction to serotonin (5-hydroxytryptamine [5-HT])
      in atherosclerotic vessels plays a crucial role in the development of myocardial
      ischemia. We investigated mechanisms for serotonin-evoked hypercontraction in
      atherosclerotic rabbit coronary arteries. METHODS AND RESULTS: Contractile
      responses to serotonergic agents of endothelium-denuded coronary arteries from
      control and Watanabe heritable hyperlipidemic rabbits (WHHL) were examined. WHHL
      coronary arteries exhibited hypercontraction to 5-HT(1)-receptor agonists; the
      constrictor threshold concentrations and E:D(50) to serotonin, 5
      carboxamidotryptamine, and sumatriptan in WHHL were significantly lower, and the
      E:(max) in WHHL to these agents were increased 55% to 59% above those of the
      control. Serotonin-evoked contractions in both groups were inhibited by GR127935
      (5-HT(1B/1D) antagonist; 0.1 to 1 nmol/L) and pertussis toxin but not by
      ketanserin (5-HT(2) antagonist; 0.01 to 1 micromol/L), suggesting that the
      hypercontraction is most likely mediated by 5-HT(1B/1D) receptors through a
      pertussis toxin-sensitive pathway. Furthermore, simultaneous measurements of
      [Ca(2+)](i) and isometric tension of fura-2-loaded arteries revealed that the
      hypercontraction was concomitant with the augmented elevation of [Ca(2+)](i) in
      the smooth muscle. The 5-HT(1B) mRNA levels in WHHL coronary arteries increased
      to 2.5-fold over those in control arteries, whereas neither 5-HT(1D) nor 5-HT(2A)
      mRNA was detected in either group. CONCLUSIONS: Atherosclerotic rabbit coronary
      arteries exhibited the enhancement in contraction and Ca(2+) mobilization in
      response to serotonin. The 5-HT(1B) receptor, which is upregulated by
      atherosclerosis, most likely mediates the augmenting effects of serotonin.

PMID- 11238276
TI  - Functional significance of hemodynamic overload-induced expression of leukemia
      inhibitory factor in the adult mammalian heart.
AB  - BACKGROUND: Leukemia-inhibitory factor (LIF) is a member of the interleukin-6
      family of cytokines that utilize gp130 as a common signaling component. In the
      present study, we examined the mechanisms that govern LIF expression and
      functional effects in the adult heart. METHODS AND RESULTS: LIF mRNA and protein
      biosynthesis were examined in the adult feline heart after hemodynamic
      overloading ex vivo. Both LIF mRNA and protein expression were detected within 60
      to 90 minutes after hemodynamic overloading. Studies in isolated adult cardiac
      myocytes showed that these cells synthesized both LIF mRNA and protein. The
      functional effects of LIF in the heart were demonstrated by studies that showed
      that LIF stimulation led to a significant increase in general protein synthesis
      and an increase in sarcomeric protein synthesis. Pretreatment with LIF also
      protected the cells against hypoxia/reoxygenation-induced cardiac myocyte
      apoptosis and cellular injury. Finally, LIF had no effect on isolated cardiac
      myocyte cell motion. CONCLUSIONS: Hemodynamic overload is a sufficient stimulus
      for LIF expression in the adult mammalian heart. Given that LIF confers both
      hypertrophic and cytoprotective responses in adult cardiac myocytes, this study
      suggests that the expression of LIF within the heart may play an important role
      in mediating homeostatic responses within the myocardium.

PMID- 11238277
TI  - Characterization of sodium channel alpha- and beta-subunits in rat and mouse
      cardiac myocytes.
AB  - BACKGROUND: Sodium channels isolated from mammalian brain are composed of alpha-,
      beta(1)-, and beta(2)-subunits. The composition of sodium channels in cardiac
      muscle, however, has not been defined, and disagreement exists over which beta
      subunits are expressed in the myocytes. Some investigators have demonstrated
      beta(1) expression in heart. Others have not detected any auxiliary subunits. On
      the basis of Northern blot analysis of total RNA, beta(2) expression has been
      thought to be exclusive to neurons and absent from cardiac muscle. METHODS AND
      RESULTS: The goal of this study was to define the subunit composition of cardiac
      sodium channels in myocytes. We show that cardiac sodium channels are composed of
      alpha-, beta(1)-, and beta(2)-subunits. Nav1.5 and Nav1.1 are expressed in
      myocytes and are associated with beta(1)- and beta(2)-subunits.
      Immunocytochemical localization of Nav1.1, beta(1), and beta(2) in adult heart
      sections showed that these subunits are expressed at the Z lines, as shown
      previously for Nav1.5. Coexpression of Nav1.5 with beta(2) in transfected cells
      resulted in no detectable changes in sodium current. CONCLUSIONS: Cardiac sodium
      channels are composed of alpha- (Nav1.1 or Nav1.5), beta(1)-, and beta(2)
      subunits. Although beta(1)-subunits modulate cardiac sodium channel current,
      beta(2)-subunit function in heart may be limited to cell adhesion.

PMID- 11238279
TI  - Short- and long-term effects of amiodarone on the two components of cardiac
      delayed rectifier K(+) current.
AB  - BACKGROUND: Amiodarone is the most promising drug for the treatment of life
      threatening tachyarrhythmias in patients with structural heart disease. The
      pharmacological effects of amiodarone on cardiac ion channels are complex and may
      differ for short-term and long-term administration. METHODS AND RESULTS: The
      delayed rectifier K(+) current (I(K)) of ventricular myocytes isolated from
      rabbit hearts was recorded with the whole-cell voltage-clamp technique. I(K) was
      separated into 2 components by use of specific blockers for either I(Ks)
      (chromanol 293B, 30 micromol/L) or I(Kr) (E-4031, 10 micromol/L). Short-term
      application of amiodarone caused a concentration-dependent decrease in I(Kr) with
      an IC(50) of 2.8 micromol/L (n=8) but only a minimal reduction in I(Ks). The
      short-term effects of amiodarone were also determined in Xenopus oocytes
      expressing the cloned human channels that conduct I(Kr) and I(Ks) (HERG and
      KvLQT1/minK). HERG current in oocytes was reduced by amiodarone (IC(50)=38
      micromol/L), whereas KvLQT1/minK current was unaffected by 300 micromol/L
      amiodarone. To study the effects of long-term drug administration, rabbits were
      treated for 4 weeks with oral amiodarone (100 mg. kg(-1). d(-1)) before cell
      isolation. Long-term administration of amiodarone decreased I(K) to 55% (n=10) in
      control rabbits and altered the relative density of I(Kr) and I(Ks). The majority
      (92%) of current was I(Kr). mRNA levels of rabbit ERG,KVLQT1, and minK in left
      ventricular myocardium did not differ between control and long-term amiodarone.
      CONCLUSIONS: Amiodarone has differential effects on the 2 components of I(K),
      depending on the application period; short-term treatment inhibits primarily
      I(Kr), whereas long-term treatment reduces I(Ks).

PMID- 11238278
TI  - In vivo ventricular gene delivery of a beta-adrenergic receptor kinase inhibitor
      to the failing heart reverses cardiac dysfunction.
AB  - BACKGROUND: Genetic manipulation to reverse molecular abnormalities associated
      with dysfunctional myocardium may provide novel treatment. This study aimed to
      determine the feasibility and functional consequences of in vivo beta-adrenergic
      receptor kinase (betaARK1) inhibition in a model of chronic left ventricular (LV)
      dysfunction after myocardial infarction (MI). METHODS AND RESULTS: Rabbits
      underwent ligation of the left circumflex (LCx) marginal artery and implantation
      of sonomicrometric crystals. Baseline cardiac physiology was studied 3 weeks
      after MI; 5x10(11) viral particles of adenovirus was percutaneously delivered
      through the LCx. Animals received transgenes encoding a peptide inhibitor of
      betaARK1 (Adeno-betaARKct) or an empty virus (EV) as control. One week after gene
      delivery, global LV and regional systolic function were measured again to assess
      gene treatment. Adeno-betaARKct delivery to the failing heart through the LCx
      resulted in chamber-specific expression of the betaARKct. Baseline in vivo LV
      systolic performance was improved in Adeno-betaARKct-treated animals compared
      with their individual pre-gene delivery values and compared with EV-treated
      rabbits. Total beta-AR density and betaARK1 levels were unchanged between
      treatment groups; however, beta-AR-stimulated adenylyl cyclase activity in the LV
      was significantly higher in Adeno-betaARKct-treated rabbits compared with EV
      treated animals. CONCLUSIONS: In vivo delivery of Adeno-betaARKct is feasible in
      the infarcted/failing heart by coronary catheterization; expression of betaARKct
      results in marked reversal of ventricular dysfunction. Thus, inhibition of
      betaARK1 provides a novel treatment strategy for improving the cardiac
      performance of the post-MI heart.

PMID- 11238280
TI  - Adenosine enhances neuroexcitability by inhibiting a slow postspike
      afterhyperpolarization in rabbit vagal afferent neurons.
AB  - BACKGROUND: Electrophysiological mechanisms by which adenosine may activate
      cardiac afferent neurons are unknown. Slow afterhyperpolarizations (AHPs) follow
      action potentials in a subset of vagal C afferents, rendering them inexcitable.
      The purpose of this study was to test the hypothesis that adenosine increases
      vagal neuronal excitability by blocking slow AHPs and to determine the adenosine
      receptor subtype mediating these effects. METHODS AND RESULTS: Using the
      perforated patch-clamp technique, we identified cultured adult rabbit nodose
      ganglion cells with slow AHPs in current-clamp mode. Trains of 100 current pulses
      at 20% above threshold were injected, with an interspike interval of 100 ms, and
      the number of action potentials triggered were counted and reported as the action
      potential response rate. During adenosine (10 micromol/L), slow AHPs were
      suppressed and action potential response rate was augmented from 3.8+/-0.5% at
      baseline to 28+/-7% after adenosine (P:=0.0009). The selective A(2)-adenosine
      receptor agonist NECA but not the A(1)-adenosine agonist CCPA replicated the
      adenosine effect. The selective A(2A)-adenosine antagonist ZM 241385 (10 nmol/L)
      but not the A(1) adenosine antagonist DPCPX (5 micromol/L) abolished the
      adenosine effect. We considered two alternative hypotheses: (1) A(2)-receptor
      mediated suppression of I(Ca) leading to smaller increases in intracellular Ca
      during stimulation, resulting in less activation of I(K(Ca)) and consequent
      suppression of slow AHPs, or (2) A(2)-receptor-mediated elevation of cAMP
      directly suppressing slow AHPs. Under voltage-clamp conditions, adenosine did not
      significantly inhibit I(Ca), making the latter hypothesis more likely.
      CONCLUSIONS: Adenosine inhibits slow AHPs in vagal afferent neurons. This effect
      is most likely caused by A(2A)-receptor-mediated stimulation of cAMP production.

PMID- 11238282
TI  - Tissue rupture and bubble formation during radiofrequency catheter ablation:
      "echoes of a pop".

PMID- 11238281
TI  - Long-term efficacy of intracoronary irradiation in inhibiting in-stent
      restenosis.
AB  - BACKGROUND: Intracoronary irradiation is a promising modality for inhibition of
      in-stent restenosis. Results of randomized clinical trials at 6 months after
      gamma ray irradiation are highly encouraging. The first results at 3 years after
      irradiation, while still showing benefit, have shown significant late loss. The
      probable mechanism of the radiation is to inactivate (prevent from dividing) most
      cells that otherwise could proliferate to produce neointimal formation. We
      measured the proportion of cells that survive with their clonogenic potential
      intact after the doses and dose rates used in the randomized trials, and we then
      modeled the subsequent repopulation of the surviving cells that might cause late
      restenosis. METHODS AND RESULTS: Human aortic smooth muscle cells were irradiated
      with gamma rays, including the doses and dose rates used in current trials, and
      clonogenic surviving fractions were measured. The subsequent repopulation of the
      surviving cells was modeled with the assumption that the repopulation kinetics
      were similar to those in unirradiated cells. The radiation is expected to delay
      the time to restenosis by factors of approximately 6 to 8, depending on the dose,
      shifting the delay from a median of 6 months (for no irradiation) to median
      values from 36 months (for a nominal 13 Gy) to 43 months (for a nominal 15 Gy).
      CONCLUSIONS: These results and predictions are quantitatively consistent with
      clinical results and suggest that clonogenic inactivation (prevention of cellular
      division) is the dominant mechanism of radiation action in the delay of
      restenosis. Intracoronary radiotherapy is a very promising modality for
      significantly delaying, although probably not preventing, in-stent restenosis.

PMID- 11238283
TI  - Images in cardiovascular medicine: Pulmonary valve endocarditis.

PMID- 11238285
TI  - Myocardial infarction redefined: role of cardiac troponin testing.

PMID- 11238286
TI  - Signal amplification in time-resolved fluorometry.

PMID- 11238288
TI  - Miniaturization technologies for molecular diagnostics.
AB  - BACKGROUND: Molecular diagnostics devices are becoming smaller. With the
      advancement of miniaturization technologies, microchip-based systems will soon be
      available for genetic testing. The purpose of this review is to highlight the
      underlying principles in miniaturization, the strategies being developed for
      bioanalysis, and the potential impact on the practice of this rapidly growing
      medical discipline. APPROACH: The author discusses DNA microchips and their
      practical importation into the clinical laboratory, based on his background in
      medical device and microchip design and development. His discussion is supported
      by a body of literature covering both biomedical and electrical engineering and
      more recent publications in the field of molecular genetics and pathology.
      CONTENT: This review is descriptive and intended to outline the technologic and
      methodologic approaches to the creation of an integrated genetic analysis
      instrument based on miniature components. The review draws on published
      scientific evaluations of these devices without regard to the companies involved
      in their development. SUMMARY: The intent of this review is that the reader will
      better understand the variety of technical approaches toward the miniaturization
      of molecular genetic testing for the clinical laboratory. With insight into the
      principles underlying the operation of these chips and the integrated systems,
      the end user can better evaluate the value to the field in terms of making
      molecular genetics testing simpler, faster, and less expensive.

PMID- 11238289
TI  - High-sensitivity C-reactive protein: a novel and promising marker of coronary
      heart disease.
AB  - BACKGROUND: Coronary heart disease remains the leading cause of morbidity and
      mortality in the industrialized world. Clinical and laboratory studies have shown
      that inflammation plays a major role in the initiation, progression, and
      destabilization of atheromas. C-Reactive protein (CRP), an acute phase reactant
      that reflects low-grade systemic inflammation, has been studied in a variety of
      cardiovascular diseases. APPROACH: Findings from prospective clinical trials were
      examined to determine the prognostic utility of CRP in acute coronary syndromes,
      and observations from epidemiological studies were reviewed to determine the
      ability of CRP to predict future first coronary events. The analytical
      considerations of CRP measurement in these clinical applications were also
      examined. CONTENT: In patients with established coronary disease, CRP has been
      shown to predict adverse clinical events. In addition, prospective studies have
      consistently shown that CRP is a strong predictor of future coronary events in
      apparently healthy men and women. The relative risk associated with CRP is
      independent of other cardiovascular disease risk factors. High-sensitivity CRP
      (hs-CRP) assays are needed for risk assessment of cardiovascular disease. Such
      assays are currently available but may require further standardization because
      patients' results will be interpreted using population-based cutpoints.
      Preventive therapies to attenuate coronary risk in individuals with increased hs
      CRP concentrations include aspirin and statin-type drugs. SUMMARY: hs-CRP has
      prognostic utility in patients with acute coronary syndromes and is a strong
      independent predictor of future coronary events in apparently healthy subjects.

PMID- 11238290
TI  - Cardiac troponin T predicts long-term outcomes in hemodialysis patients.
AB  - BACKGROUND: Increased plasma troponin T (cTnT), but not troponin I (cTnI), is
      frequently observed in end-stage renal failure patients. Although generally
      considered spurious, we previously reported an associated increased mortality at
      12 months. METHODS: We studied long-term outcomes in 244 patients on chronic
      hemodialysis for up to 34 months, correlating the outcomes to plasma cTnT in
      routine predialysis samples. In addition, subsequent plasma samples at least 1
      year later and within 6 months of data analysis were available in 97 patients and
      were used to identify patients with increasing plasma cTnT. The endpoints used
      were death and new or worsening coronary, cerebro-, and peripheral vascular
      disease and neuropathy. RESULTS: Transplantation occurred more frequently in
      patients with low initial cTnT: 31%, 13%, and 3% in the groups with cTnT < 0.010,
      0.010-0.099, and > or = 0.100 microg/L, respectively. In the same groups, total
      deaths occurred in 6%, 43%, and 59% and cardiac deaths in 0%, 14%, and 24% of
      patients. In patients with follow-up samples, the group with increasing cTnT had
      a significantly increased death (relative risk, 2.0; P = 0.028). The increase was
      mainly in cardiac and sudden deaths. CONCLUSIONS: Higher plasma cTnT predicts
      long-term all-cause mortality in hemodialysis patients, even at concentrations <
      0.100 microg/L, as does an increasing cTnT concentration over time.

PMID- 11238291
TI  - Evaluation of nine automated high-sensitivity C-reactive protein methods:
      implications for clinical and epidemiological applications. Part 2.
AB  - BACKGROUND: C-Reactive protein (CRP) can provide prognostic information about
      risk of future coronary events in apparently healthy subjects. This application
      requires higher sensitivity assays than have traditionally been available in the
      clinical laboratory. METHODS: Nine high-sensitivity CRP (hs-CRP) methods from
      Dade Behring, Daiichi, Denka Seiken, Diagnostic Products Corporation, Iatron,
      Kamiya, Olympus, Roche, and Wako were evaluated for limit of detection,
      linearity, precision, prozone effect, and comparability with samples from 388
      apparently healthy individuals. RESULTS: All methods had limits of detection that
      were lower than the manufacturers' claimed limit of quantification except for the
      Kamiya, Roche, and Wako methods. All methods were linear at 0.3-10 mg/L. The
      Diagnostic Products Corporation, Kamiya, Olympus, and Wako methods had
      imprecision (CVs) >10% at 0.15 mg/L. The Iatron, Olympus, and Wako methods
      demonstrated prozone effects at hs-CRP concentrations of 12, 206, and 117 mg/L,
      respectively. hs-CRP concentrations demarcating each quartile in a healthy
      population were method-dependent. Ninety-two to 95% of subjects were classified
      into the same quartile of hs-CRP established by the Dade Behring method by the
      Denka Seiken, Diagnostic Products Corporation, Iatron, and Wako methods. In
      contrast, 68-77% of subjects were classified into the same quartile by the
      Daiichi, Kamiya, Olympus, and Roche methods. No subject varied by more than one
      quartile by any method. CONCLUSIONS: Four of the nine examined hs-CRP methods
      classified apparently healthy subjects into quartiles of hs-CRP similar to the
      classifications assigned by the comparison method. Additional standardization
      efforts are required because an individual patient's results will be interpreted
      using population-based cutpoints.

PMID- 11238293
TI  - Standardization of cardiac troponin I assays: round Robin of ten candidate
      reference materials.
AB  - BACKGROUND: Cardiac troponin I (cTnI) results vary 100-fold among assays. As a
      step toward standardization, we examined the performance of 10 candidate
      reference materials (cRMs) in dilution studies with 13 cTnI measurement systems.
      METHODS: Solutions of 10 cTnI cRMs, each characterized by NIST, were shipped to
      the manufacturers of 13 cTnI measurement systems. Manufacturers used their
      respective diluents to prepare each cRM in cTnI concentrations of 1, 10, 25, and
      50 microg/L. For the purpose of ranking the cRMs, the deviation of each cTnI
      measurement from the expected response was assessed after normalization with the
      10 microg/L cTnI solution. Normalized deviations were examined in five formats.
      Parameters from linear regression analysis of the measured cTnI vs expected
      values were also used to rank performance of the cRMs. RESULTS: The three cRMs
      demonstrating the best overall rankings were complexes of troponins C, I, and T.
      The matrices for these three cRMs values differed; one was reconstituted directly
      from the lyophilized form submitted by the supplier; one was submitted in liquid
      form, lyophilized at NIST, and subsequently reconstituted; and the third was
      evaluated in the liquid form received from the supplier. The cRM demonstrating
      the fourth best performance was a binary complex of troponins C and I supplied in
      lyophilized form and reconstituted before distribution. CONCLUSIONS: The cRMs
      demonstrating the best performance characteristics in 13 cTnI analytical systems
      will be included in subsequent activities of the cTnI Standardization Committee
      of the AACC.

PMID- 11238292
TI  - Absence of diurnal variation of C-reactive protein concentrations in healthy
      human subjects.
AB  - BACKGROUND: The concentration of C-reactive protein (CRP) in otherwise healthy
      subjects has been shown to predict future risk of myocardial infarction and
      stroke. CRP is synthesized by the liver in response to interleukin-6, the serum
      concentration of which is subject to diurnal variation. METHODS: To examine the
      existence of a time-of-day effect for baseline CRP values, we determined CRP
      concentrations in hourly blood samples drawn from healthy subjects (10 males, 3
      females; age range, 21-35 years) during a baseline day in a controlled
      environment (8 h of nighttime sleep). RESULTS: Overall CRP concentrations were
      low, with only three subjects having CRP concentrations >2 mg/L. Comparison of
      raw data showed stability of CRP concentrations throughout the 24 h studied. When
      compared with cutoff values of CRP quintile derived from population-based
      studies, misclassification of greater than one quintile did not occur as a result
      of diurnal variation in any of the subjects studied. Nonparametric ANOVA
      comparing different time points showed no significant differences for both raw
      and z-transformed data. Analysis for rhythmic diurnal variation using a method
      fitting a cosine curve to the group data was negative. CONCLUSIONS: Our data show
      that baseline CRP concentrations are not subject to time-of-day variation and
      thus help to explain why CRP concentrations are a better predictor of vascular
      risk than interleukin-6. Determination of CRP for cardiovascular risk prediction
      may be performed without concern for diurnal variation.

PMID- 11238294
TI  - Compound heterozygous familial hypercholesterolemia and familial defective
      apolipoprotein B-100 produce exaggerated hypercholesterolemia.
AB  - BACKGROUND: Familial hypercholesterolemia (FH) and familial defective
      apolipoprotein B-100 (FDB) represent ligand-receptor disorders that are
      complementary. Individuals with both FH and FDB are unusual. We report a family
      with both disorders and the impact of the mutations on the phenotypes of the
      family members. METHODS: We used single strand conformation polymorphism (SSCP)
      and denaturing gradient gel electrophoresis (DGGE) for genetic analysis of all 18
      exons and the promoter region of the LDL receptor and DGGE for genetic analysis
      of the apolipoprotein B-100 (apo B-100) gene. The functional significance of the
      apo B-100 mutation was studied using a U937 cell proliferation assay. Fasting
      serum lipid profiles were determined for the index case and seven first-degree
      relatives. RESULTS: One of the patient's sisters had a missense mutation
      (Asp(407)-->Lys) in exon 9 of the LDL receptor and a serum LDL-cholesterol
      concentration of 4.07 mmol/L. Four other first-degree relatives had
      hyperlipidemia but no LDL-receptor mutation. However, these subjects had a
      mutation of the apo B-100 gene (Arg(3500)-->Trp). The cell proliferation rate of
      U937 cells fed with LDL from other subjects with the same mutation was fourfold
      less than that of controls. The index case had both FH- and FDB-related
      mutations. Her serum LDL-cholesterol (9.47 mmol/L) was higher than all other
      relatives tested. CONCLUSIONS: Existence of both FH and FDB should be considered
      in families with LDL-receptor mutations in some but not all individuals with
      hypercholesterolemia or when some individuals in families with FH exhibit
      exaggerated hypercholesterolemia.

PMID- 11238295
TI  - Variability and classification accuracy of serial high-sensitivity C-reactive
      protein measurements in healthy adults.
AB  - BACKGROUND: Increased concentrations of high-sensitivity C-reactive protein (hs
      CRP), a marker of systemic inflammation, are associated with increased risk for
      coronary heart disease. Because of its relationship to inflammation, hs-CRP has
      considerable biologic variation. This study was carried out to characterize CRP
      variation and to compare it to another risk factor, total serum cholesterol.
      METHODS: One hundred thirteen individuals were scheduled to have five
      measurements each of hs-CRP and total cholesterol carried out at quarterly
      intervals over a 1-year period. Variations of hs-CRP and total cholesterol were
      characterized, and classification accuracy was described and compared for both.
      RESULTS: The relative variation was comparable for hs-CRP and total cholesterol.
      When classified by quartile, 63% of first and second hs-CRP measurements were in
      agreement; for total cholesterol it was 60%. Ninety percent of hs-CRP
      measurements were within one quartile of each other. This relationship was not
      altered by the use of log-transformed hs-CRP data. CONCLUSION: hs-CRP has a
      degree of measurement stability that is similar to that of total cholesterol.

PMID- 11238296
TI  - Clinical and experimental results on cardiac troponin expression in Duchenne
      muscular dystrophy.
AB  - BACKGROUND: Because of controversial earlier studies, the purpose of this study
      was to provide novel experimental and additional clinical data regarding the
      possible reexpression of cardiac troponin T (cTnT) in regenerating skeletal
      muscle in Duchenne muscular dystrophy (DMD). METHODS: Plasma from 14 patients
      (mean age, 7.5 years; range, 5.7-19.4 years) with DMD was investigated for
      creatine kinase (CK), the CK MB isoenzyme (CKMB), cTnT and cardiac troponin I
      (cTnI), and myoglobin. cTnT concentrations were measured by an ELISA (second
      generation assay; Roche) using the ES 300 Analyzer. cTnI, myoglobin, and CKMB
      were measured by an ELISA using the ACCESS System (Beckman Diagnostics). Troponin
      isoform expression was studied by Western blot analysis in remnants of skeletal
      muscle biopsies of three patients with DMD and in an animal model of DMD (mdx
      mice; n = 6). RESULTS: There was no relation of cTnT and cTnI to clinical
      evidence for cardiac failure. cTnI concentrations remained below the upper
      reference limit in all patients. cTnT was increased (median, 0.11 microg/L;
      range, 0.06-0.16 microg/L) in 50% of patients. The only significant correlation
      was found for CK (median, 3938 U/L; range, 2763-5030 U/L) with age (median, 7.5
      years; range, 6.8-10.9 years; r = -0.762; P = 0.042). Western blot analysis of
      human or mouse homogenized muscle specimens showed no evidence for cardiac TnT
      and cTnI expression, despite strong signals for skeletal muscle troponin
      isoforms. CONCLUSIONS: We found no evidence for cTnT reexpression in human early
      stage DMD and in mdx mouse skeletal muscle biopsies. Discrepancies of cTnT and
      cTnI in plasma samples of DMD patients were found, but neither cTnT nor cTnI
      plasma concentrations were related with other clinical evidence for cardiac
      involvement.

PMID- 11238297
TI  - Effects of implantable cardioverter defibrillator implantation and shock
      application on biochemical markers of myocardial damage.
AB  - BACKGROUND: Implantable cardioverter defibrillator (ICD) implantation is a common
      approach in patients at high risk of sudden cardiac death. To check for normal
      function, it is necessary to test the ICD. For this purpose, repetitive induction
      and termination of ventricular fibrillation by direct current shocks is required.
      This may lead to minor myocardial damage. Cardiac troponin T (cTnT) and I (cTnI)
      are specific markers for the detection of myocardial injury. Because these
      proteins usually are undetectable in healthy individuals, they are excellent
      markers for detecting minimal myocardial damage. The objective of this study was
      to evaluate the effect of defibrillation of induced ventricular fibrillation on
      markers of myocardial damage. METHODS: This study included 14 patients who
      underwent ICD implantation and intraoperative testing. We measured cTnT, cTnI,
      creatine kinase MB (CK-MB) mass, CK activity, and myoglobin before and at
      definite times after intraoperative shock application. RESULTS: Depending on the
      effectiveness of shocks and the energy applied, the cardiac-specific markers cTnT
      and cTnI, as well as CK-MB mass, showed a significant increase compared with the
      baseline value before testing and peaked for the most part 4 h after shock
      application. In contrast, the increases in CK activity and myoglobin were
      predominantly detectable in patients who received additional external shocks.
      CONCLUSIONS: ICD implantation and testing leads to a short release of cardiac
      markers into the circulation. This release seems to be of cytoplasmic origin and
      depends on the number and effectiveness of the shocks applied.

PMID- 11238298
TI  - Characteristics of an Albumin Cobalt Binding Test for assessment of acute
      coronary syndrome patients: a multicenter study.
AB  - BACKGROUND: The ability of the N-terminal region of human albumin to bind cobalt
      is diminished by myocardial ischemia. The characteristics of an assay based on
      albumin cobalt binding were assessed in suspected acute coronary syndrome
      patients and in a control reference population. The ability of the Albumin Cobalt
      Binding (ACB) Test measurement at presentation to predict troponin-positive or 
      negative results 6-24 h later was also examined. METHODS: We enrolled 256 acute
      coronary syndrome patients at four medical centers. Blood specimens were
      collected at presentation and then 6-24 h later. The dichotomous decision limit
      and performance characteristics of the ACB Test for predicting troponin-positive
      or -negative status 6 h-24 h later were determined using ROC curve analysis.
      Results for 32 patients could not be used because the time of onset of ischemia
      appeared to have been >3 h before presentation or was uncertain. The reference
      interval was determined by parametric analysis to estimate the upper 95th
      percentile of a reference population (n = 109) of ostensibly healthy individuals.
      RESULTS: Increased cTnI was found in 35 of 224 patients. The ROC curve area for
      the ACB Test was 0.78 [95% confidence interval (CI), 0.70-0.86]. At the optimum
      decision point of 75 units/mL, the sensitivity and specificity of the ACB Test
      were 83% (95% CI, 66-93%) and 69% (95% CI, 62-76%). The negative predictive value
      was 96% (95% CI, 91-98%), and the positive predictive value was 33% (95% CI, 24
      44%). The within-run CV of the ACB Test was 7.3%. Results for the reference
      population were normally distributed; the one-sided parametric 95th percentile
      was 80.2 units/mL. CONCLUSIONS: This exploratory study suggests that the ACB Test
      has high negative predictive value and sensitivity in the presentation sample for
      predicting troponin-negative or -positive results 6-24 h later.

PMID- 11238299
TI  - Production of recombinant human creatine kinase (r-hCK) isozymes by tandem repeat
      expression of M and B genes and characterization of r-hCK-MB.
AB  - BACKGROUND: Serum creatine kinase-MB isoenzyme (CK-MB) is widely used as a marker
      of myocardial injury. We prepared recombinant human CK (r-hCK) MB isoenzyme and
      examined its potential for use as a control material for assay of CK-MB in serum.
      METHODS: cDNAs encoding CK-M and CK-B subunits were inserted into the same
      plasmid vector, followed by transformation of Escherichia coli. The resulting
      three types of CK isoenzymes were purified by conventional chromatography.
      RESULTS: The ratio of MB to MM to BB was 50:40:10 on the basis of CK activity.
      Highly purified CK-MB with a specific activity of 533 U/mg was produced in a
      yield of 5.7 mg/g of packed cells. Purified r-hCK-MB had the isoelectric point
      (pI 5.3) and molecular size (46 kDa for the subunit) of native CK-MB. Its
      immunoreactivity in an ELISA using antibody against native heart enzyme was
      similar to that of cardiac CK-MB. The r-hCK-MB retained >90% activity for at
      least 4 months at 11 degrees C in a delipidated serum matrix in a liquid form at
      a concentration of 118 U/L. CONCLUSIONS: r-hCK-MB shows key properties of the
      native cardiac isoenzyme and may be useful as a control and calibrator for serum
      assays of CK-MB.

PMID- 11238300
TI  - Diagnosis of dopa-responsive dystonia and other tetrahydrobiopterin disorders by
      the study of biopterin metabolism in fibroblasts.
AB  - BACKGROUND: Dopa-responsive dystonia (DRD) and tetrahydrobiopterin (BH4) defects
      are inherited disorders characterized by monoamine neurotransmitter deficiency
      with decreased activity of one of the BH4-metabolizing enzymes. The aim of the
      study was to determine the utility of cultured skin fibroblasts for the diagnosis
      of these diseases. METHODS: Neopterin and biopterin production and GTP
      cyclohydrolase I (GTPCH) activity were measured in cytokine-stimulated
      fibroblasts; 6-pyruvoyltetrahydropterin synthase (PTPS), sepiapterin reductase
      (SR), and dihydropteridine reductase (DHPR) activities were measured in
      unstimulated fibroblasts. We examined 8 patients with DRD, 3 with autosomal
      recessive GTPCH deficiency, 7 with PTPS deficiency, 3 with DHPR deficiency, and
      49 controls (35 fibroblast and 14 amniocyte samples). RESULTS: Fibroblasts from
      patients with DRD and autosomal recessive GTPCH deficiency showed reduced GTPCH
      activity (15.4% and 30.7% of normal activity, respectively) compared with
      controls (P < 0.001). Neopterin production was very low and biopterin production
      was reduced in both disorders. PTPS- and DHPR-deficient cells showed no enzyme
      activities; in PTPS deficiency the pattern of pterin production was typical
      (neopterin, 334-734 pmol/mg; controls, 18-98 pmol/mg; biopterin, 0 pmol/mg;
      controls, 154-303 pmol/mg). Reference values of all enzyme activities and pterin
      production were measured in fibroblasts and also in amniocytes for prenatal
      diagnosis. CONCLUSIONS: Cultured skin fibroblasts are a useful tool in the
      diagnosis of BH4 deficiencies. Intracellular neopterin and biopterin
      concentrations and GTPCH activity in cytokine-stimulated fibroblasts are
      particularly helpful in diagnosing patients with DRD.

PMID- 11238301
TI  - Simultaneous absolute quantification of target and control templates by real-time
      fluorescence reverse transcription-PCR using 4-(4'-dimethylaminophenylazo)benzoic
      acid as a dark quencher dye.
AB  - BACKGROUND: Despite the many advantages of real-time fluorescence reverse
      transcription-PCR (RT-PCR) as a quantitative analytical tool, simultaneous
      quantification of target and reference templates within one reaction has not been
      reported. We developed such an assay with an internal reference template.
      METHODS: For quantification of target and reference sequences, we used two
      fluorescent probes in one reaction vessel on an ABI PRISM 7700 SDS instrument.
      Fluorescent probes were labeled with either 6-carboxy-fluorescein or hexachloro-6
      carboxy-fluorescein as reporter dye and 4-(4'-dimethylaminophenylazo)benzoic acid
      (DABCYL) as a dark quencher fluorophore. To test the sensitivity and specificity
      of this assay, serial dilutions of reference and target templates were analyzed
      in one PCR reaction. In the presence of 10 beta-actin molecules as control
      templates, 10(5) bcr/abl molecules were amplified, and 10(5) beta-actin molecules
      were amplified in the presence of 10 bcr/abl copies. We also performed single and
      duplex measurements on samples from five patients with documented Philadelphia
      chromosome-positive chronic myelogenous leukemia disease courses (72 samples) and
      three with minor bcr/abl+ acute myelogenous leukemias (26 samples). RESULTS: For
      M-bcr/abl duplex RT-PCR, the correlation coefficient (r) for starting template
      amounts and threshold cycle values was 0.99; for m-bcr/abl, r = 0.96, indicating
      a precise log-linear relation for 10-10(5) copies/100 ng of cDNA. In the same PCR
      reactions, r = 0.99 for beta-actin (coamplified with M-bcr/abl or m-bcr/abl) for
      10(3)-10(7) copies/100 ng cDNA. The linear correlation coefficient for single and
      duplex measurements was 0.98 for M- and m-bcr/abl in patient samples.
      CONCLUSIONS: DABCYL can be used as dark quencher fluorophore in real-time
      fluorescence PCR. The duplex fluorescence RT-PCR assay for bcr/abl and beta-actin
      transcripts allows monitoring of bcr/abl+ leukemias.

PMID- 11238302
TI  - Double-gradient denaturing gradient gel electrophoresis assay for identification
      of L-ferritin iron-responsive element mutations responsible for hereditary
      hyperferritinemia-cataract syndrome: identification of the new mutation C14G.
AB  - BACKGROUND: Hereditary hyperferritinemia-cataract syndrome is an autosomic
      dominant disorder caused by heterogeneous mutations on the iron-responsive
      element (IRE) of ferritin L-chain mRNA. The mutations described to date were
      identified by direct sequencing of DNA from probands with hyperferritinemia often
      associated to bilateral cataracts. A direct genetic approach on a large
      population is useful to recognize polymorphisms in the DNA region and the
      prevalence of mutations associated with minor increases in serum ferritin and
      subclinical cataracts. We developed a rapid DNA scanning technique to detect
      mutations in a single electrophoretic analysis. METHODS: The double-gradient
      denaturing gradient gel electrophoresis (DG-DGGE) method consisted of PCR
      amplification of the target genomic DNA with GC-clamped oligonucleotides. The
      sequence encoded the 5' untranslated flanking region of ferritin L-chain mRNA,
      which includes an IRE stem-loop structure. The product was subjected to DG-DGGE
      (8.5-15% polyacrylamide and 50-95% denaturant) to separate the homo- and
      heteroduplexes. RESULTS: The method clearly identified all eight accessible
      mutations, including C-G transversions, which are the most difficult to detect.
      The method was applied to scan DNA samples from 50 healthy subjects and from 230
      subjects with serum ferritin >400 microg/L. The new mutation G14C was identified.
      CONCLUSIONS: The DG-DGGE method detects all the mutations in the L-ferritin IRE
      sequence, is rapid and economical, and can be applied to scan large populations.
      The first population study indicated that the mutations are rare and may involve
      regions of the IRE structure not yet characterized.

PMID- 11238303
TI  - Solid-phase PCR with hybridization and time-resolved fluorometry for detection of
      HLA-B27.
AB  - BACKGROUND: Preactivated solid surfaces provide new possibilities for multiple
      consecutive reactions in a microtiter plate format. In this study, a combination
      of PCR and subsequent hybridization in the same microtiter well was applied for
      the detection of HLA-B27 alleles. METHODS: A multiplex solid-phase PCR to amplify
      the HLA-B27 alleles together with beta-actin as an amplification control gene was
      performed on the NucleoLink (Nunc) surface. PCR was followed by hybridization and
      detection with time-resolved fluorescence. For the covalent capture of the PCR
      primers onto the solid support via a 1-(3-dimethylamino-propyl)-3
      ethylcarbodiimide hydrochloride-mediated reaction, different 5'-end modifications
      of oligonucleotides were tested [amination, phosphorylation, and a poly(dT)10
      linker]. RESULTS: For covalent immobilization of the primers, amination of the 5'
      end combined with use of the poly(dT)10 linker was superior. At least 19.5% of
      the primer added per well was attached via a stable bond. When the standard time
      resolved, fluorescence-based HLA-B27 detection system was compared with the newly
      developed method in a sample series of 82 genomic DNAs and the corresponding
      dried-blood spots, all results were in full agreement. CONCLUSIONS: The new solid
      phase PCR approach can be applied for multiple-target DNA detection. PCR followed
      by hybridization can be accomplished in a few hours using precoated strips and
      dried-blood spot PCR templates.

PMID- 11238304
TI  - Molecular strategy for detecting metastatic cancers with use of multiple tumor
      specific MAGE-A genes.
AB  - BACKGROUND: The human melanoma-associated antigen family A (MAGE-A) has high
      specificity and expression in various malignancies, but individual family members
      are expressed at low frequency in any one particular type of cancer. We therefore
      developed a method to detect mRNAs from multiple MAGE-A genes in a single
      reaction. METHODS: Universal MAGE-A (uMAGE-A) primers and probe were designed to
      reverse-transcribe, amplify, and detect by electrochemiluminescence (ECL) MAGE-A
      mRNAs on the Origen Analyzer. The assay was performed on total RNA of melanoma (n
      = 9 cell lines and 24 tumors), breast cancer (n = 7 and 26), and colorectal
      cancer (CRC; n = 5 and 12). We also evaluated blood from melanoma (n = 50),
      breast cancer (n = 16), and CRC (n = 21) patients. RESULTS: The uMAGE-A mRNA was
      detectable in 0.01-1 ng of cell line RNA. The identity of the uMAGE-A cDNA
      products was confirmed by sequencing and polyacrylamide gel electrophoresis. The
      uMAGE-A assay increased detection of melanoma, breast cancer, and CRC tumor by
      13%, 31%, and 25%, respectively, compared with a MAGE-A1 assay, and by 17%, 19%,
      and 25%, respectively, compared with a MAGE-A3 assay. The uMAGE-A assay detected
      circulating tumor cells in the blood of melanoma (24%), breast cancer (25%), and
      CRC (29%) patients. CONCLUSIONS: The uMAGE-A reverse transcription-PCR/ECL assay
      provides a practical and sensitive approach for detection of various metastatic
      cancers in tissues and blood.

PMID- 11238305
TI  - Rapid determination of transferrin isoforms by immunoaffinity liquid
      chromatography and electrospray mass spectrometry.
AB  - BACKGROUND: Congenital disorders of glycosylation (CDG) are autosomal recessive
      disorders that produce increased serum carbohydrate-deficient transferrin (CDT)
      isoforms. Methods to resolve CDT from fully glycosylated transferrin (Trf) have
      been based on a neutral shift in the isoelectric focusing (IEF) pattern or on a
      reduction in the negative charge, allowing resolution by anion-exchange
      chromatography. Our purpose was to develop a method of resolution and relative
      quantification of Trf isoforms using online immunoaffinity liquid chromatography
      mass spectrometry (LC-MS). METHODS: Serum (25 microL) was diluted with 100 microL
      of water before application to an immunoaffinity column that sequestered Trf
      isoforms. Trf isoforms were eluted from the immunoaffinity column, concentrated
      on a C4 column, eluted from the C4 column, and introduced into the mass
      spectrometer. Analysis of the Trf isoforms was entirely automated and completed
      in <10 min per sample. RESULTS: The LC-MS method demonstrated that the major
      abnormal Trf isoforms in CDG lack one complete oligosaccharide structure (mono
      oligosaccharide) or both oligosaccharide structures (a-oligosaccharide), but not
      the sialic acids, as presumed on the basis of IEF methods. Calculation of
      relative ratios among three possible species (mono-/di-oligosaccharide and a-/di
      oligosaccharide) is reproducible [mean intra- and interassay CVs were 9.3% (n =
      10) and 10% (n = 5), respectively]. A reference range for patients <18 years was
      determined by analysis of 209 samples (for mono-/di-oligosaccharide, the median
      was 0.041 and the range was 0.018-0.083; for a-/di-oligosaccharide, the median
      was 0.007 and the range was 0.002-0.036). Comparison of data obtained with an
      affinity chromatography-IEF method and the LC-MS method demonstrated equivalence
      in the interpreted results (n = 170). CONCLUSIONS: Advantages of the LC-MS method
      include improved sensitivity, minimal sample preparation, and an analysis time of
      <10 min. The method was automated, which allowed high throughput, with >100
      samples analyzed in a single day. Moreover, the nature of the oligosaccharide
      defect in CDG is accurately reflected by mass resolution, and subtle
      oligosaccharide truncations may also be detected by this method.

PMID- 11238306
TI  - Real-time quantitative telomeric repeat amplification protocol assay for the
      detection of telomerase activity.
AB  - BACKGROUND: Telomerase is a ribonucleoprotein enzyme associated with
      immortalization and transformation of human cells. The telomeric repeat
      amplification protocol (TRAP) is widely used for the detection of telomerase
      activity. The TRAP method, although highly sensitive and specific because it
      includes PCR amplification, is laborious and does not provide precise
      quantitative information. METHODS: We developed a real-time quantitative TRAP
      (RTQ-TRAP) system by combining a real-time PCR technique with the conventional
      TRAP method. Telomerase activity in human tumor cell lines and in 13 lymphoma
      samples was measured using the RTQ-TRAP assay, and the results obtained from the
      samples using the RTQ-TRAP method were compared with the conventional TRAP
      method. RESULTS: The RTQ-TRAP method was both accurate and reproducible in
      measuring telomerase activity in a dilution series of protein extracts from HL60
      cells. Telomerase activity in 13 lymphoma samples, as determined by the RTQ-TRAP
      method, was ninefold lower than that measured by the conventional TRAP method.
      The half-life of telomerase activity in human tumor cells, as determined using
      RTQ-TRAP, was much shorter than the half-life reported previously. CONCLUSIONS:
      Our results suggest that the conventional TRAP assay frequently overestimates
      telomerase activity in tumor samples. The RTQ-TRAP method is thus a useful tool
      to rapidly and precisely quantify telomerase activity.

PMID- 11238307
TI  - Development of a stable-isotope dilution assay for gamma-aminobutyric acid (GABA)
      transaminase in isolated leukocytes and evidence that GABA and beta-alanine
      transaminases are identical.
AB  - BACKGROUND: Several methods have been published for measuring gamma-aminobutyric
      acid transaminase (GABA-T) activity, but these methods are either impracticable
      because of the use of radioisotopes or insufficiently sensitive to determine
      small enzyme activities in leukocyte extracts. We developed a direct and
      sensitive enzyme method. METHODS: We developed a stable-isotope dilution method
      for the measurement of [15N]glutamic acid derived from [15N]GABA and alpha
      ketoglutaric acid, catalyzed by GABA-T. The method for analysis of [15N]glutamic
      acid comprised a solid-phase extraction procedure to isolate this analyte from
      incubation samples. After derivatization, [15N]glutamic acid was quantified by
      gas chromatography-mass spectrometry relative to its 2H5-labeled internal
      standard. In addition to [15N]GABA, [15N]beta-alanine was a cosubstrate. RESULTS:
      GABA-T-deficient lymphoblasts showed diminished enzyme activity, with both
      [15N]GABA and [15N]beta-alanine as substrate. Vigabatrin inhibited the enzyme
      activity for both substrates. CONCLUSIONS: The activity of GABA-T can be
      accurately determined by our procedure using 15N-labeled substrate, measuring the
      formation of [15N]glutamic acid. Our results with [15N]beta-alanine indicate that
      GABA and beta-alanine transaminases are identical.

PMID- 11238308
TI  - Triple lipid screening test: a homogeneous sequential assay for HDL-cholesterol,
      total cholesterol, and triglycerides.
AB  - BACKGROUND: The analysis of lipids in serum lipoprotein fractions is useful in
      assessing the risk for coronary artery disease, but it typically involves
      performing multiple tests. An automated single-tube assay, referred to as the
      triple lipid screening (TLS) test, can be used for measuring HDL-cholesterol (HDL
      C), total cholesterol, and triglycerides (TGs) with no specimen pretreatment.
      METHODS: The first part of the assay is based on a homogeneous assay for HDL-C
      that uses either an anti-apolipoprotein B antibody (TLS-A test) or a polyanion
      (TLS-B test) that blocks the enzymatic measurement of cholesterol on the non-HDL
      fraction. After the addition of deoxycholate, which solubilizes the unreacted
      cholesterol from the non-HDL fraction, the remaining cholesterol in the sample is
      subsequently measured enzymatically. Using the same enzyme detection system as
      the cholesterol assay, TGs are measured in the last step, after the addition of
      the enzymes for the TG assay. RESULTS: The TLS assay (y) had acceptable analytic
      performance and compared favorably with standard tests (x) for each analyte: for
      HDL-C, TLS-A = 0.99x + 0.19 (R = 0.980); TLS-B = 1.00x - 0.15 (R = 0.974); for
      total cholesterol, TLS-A = 1.03x + 0.12 (R = 0.997); TLS-B = 1.07x - 0.30 (R =
      0.965); and for TGs, TLS-A = 1.02x + 0.02 (R = 0.988); TLS-B = 1.04x - 0.28 (R =
      0.980). CONCLUSIONS: The TLS test is a single-tube homogeneous assay for the
      analysis of all of the major serum lipoprotein fractions and can be used as a
      simple screening test for the detection of hyperlipidemia.

PMID- 11238309
TI  - Comparison of ELISAs for opiates, methamphetamine, cocaine metabolite,
      benzodiazepines, phencyclidine, and cannabinoids in whole blood and urine.
AB  - BACKGROUND: ELISAs are widely utilized in forensic drug analysis. A comparative
      assessment of microtiter plate assays for the detection of six common classes of
      drug in blood and urine is described. METHODS: ELISAs for opiates,
      methamphetamine, benzodiazepines, cocaine metabolite, phencyclidine (PCP), and
      tetrahydrocannabinol (THC) metabolite were evaluated in a side-by-side study. The
      analytical performance of 12 commercially available ELISAs was determined in
      terms of binding characteristics, dose-response curves, limits of detection,
      sensitivity, intra- and interassay imprecision, and lot-to-lot reproducibility.
      Assay performance was also compared using 855 forensic casework samples. RESULTS:
      Detection limits in whole blood for morphine, D-methamphetamine, nordiazepam,
      benzoylecgonine, nordiazepam, PCP, and L-11-nor-9-carboxy-delta9-THC were 3, 2,
      <4, 5, 25, and 3 microg/L, respectively, for the STC ELISAs. Corresponding
      detection limits for Immunalysis ELISAs were <1, <2, <4, 5, <1, and 1 microg/L,
      respectively. Intraassay CVs (n = 8) at the immunoassay cutoff concentrations
      were 4.1-5.6% and 3.5-11% for STC and Immunalysis ELISAs, respectively.
      Corresponding interassay CVs were 3.1-10% and 6.5-20%. Of the 855 casework
      samples, there were a total of 92 discordant results (44 cannabinoid, 15 opiate,
      15 methamphetamine, 11 benzodiazepine, and 7 cocaine metabolite). Gas
      chromatography-mass spectrometry analysis indicated a total of three unconfirmed
      positive results for Immunalysis assays and one unconfirmed positive for STC
      assays. CONCLUSIONS: A comparative assessment of drugs-of-abuse assays from two
      manufacturers indicated some key differences in analytical performance. Overall,
      Immunalysis assays offered superior binding characteristics and detection limits,
      whereas STC assays offered improved overall precision and lot-to-lot
      reproducibility.

PMID- 11238310
TI  - High-throughput genotyping of thiopurine S-methyltransferase by denaturing HPLC.
AB  - BACKGROUND: The thiopurine S:-methyltransferase (TPMT) genetic polymorphism has a
      significant clinical impact on the toxicity of thiopurine drugs, which are used
      in the treatment of leukemia and as immunosuppressants. To date, 10 mutant
      alleles are known that are associated with intermediate or low TPMT activity. To
      facilitate rapid screening of clinically relevant TPMT mutations, we developed a
      strategy of high-throughput genotyping by applying denaturing HPLC (DHPLC).
      METHODS: To test the specificity and efficiency of the DHPLC method, 98 DNA
      samples from a selected population of patients receiving thiopurine therapy or
      with previous thiopurine withdrawal were analyzed for the most frequent mutant
      TPMT alleles, *2 and *3A, which contain key mutations in exons 5, 7, and 10 to
      identify clearly different elution profiles. All fragments were examined by
      direct sequencing. Additionally, to test the sensitivity of DHPLC analysis,
      genotyping for the *2 and *3A alleles of all 98 DNA samples was performed by PCR
      based methods (PCR-restriction fragment polymorphism analysis and allele-specific
      PCR). RESULTS: The presence of mutations discriminating for alleles *2, *3A, *3C,
      and *3D, as well as various silent and intron mutations, were correctly predicted
      by DHPLC in 100% of the samples as confirmed by direct sequencing. Comparison
      with PCR-based methods for alleles *2 and *3 produced an agreement of 100% with
      no false-negative signals. CONCLUSIONS: DHPLC offers a highly sensitive, rapid,
      and efficient method for genotyping of the relevant TPMT mutations,
      discriminating at least for alleles *2 and *3, in clinical and laboratory
      practice. Additionally, DHPLC allows a simultaneous screening for novel genetic
      variability in the TPMT gene.

PMID- 11238311
TI  - Automated flow cytometric analysis of cerebrospinal fluid.
AB  - BACKGROUND: Recently, the UF-100 (Sysmex Corporation) flow cytometer was
      developed to automate urinalysis. We evaluated the use of flow cytometry in the
      analysis of cerebrospinal fluid (CSF). METHODS: UF-100 data were correlated with
      microscopy and biochemical data for 256 CSF samples. Microbiological analysis was
      performed in 144 suspected cases of meningitis. RESULTS: Good agreement was
      obtained between UF-100 and microscopy data for erythrocytes (r = 0.919) and
      leukocytes (r = 0.886). In some cases, however, incorrect classification of
      lymphocytes by the UF-100 led to underestimation of the leukocyte count. UF-100
      bacterial count positively correlated (P < 0.001) with UF-100 leukocyte count (r
      = 0.666), CSF total protein (r = 0.754), and CSF lactate concentrations (r =
      0.641), and negatively correlated with CSF glucose concentration (r = -0.405; P <
      0.001). UF-100 bacterial counts were unreliable in hemorrhagic samples and in
      samples collected by ventricular drainage where interference by blood platelets
      and cell debris was observed. Another major problem was the UF-100 "bacterial"
      background signal in sterile CSF samples. Cryptococcus neoformans yeast cells and
      cholesterol crystals in craniopharyngioma were detected by the flow cytometer.
      CONCLUSIONS: Flow cytometry of CSF with the UF-100 offers a rapid and reliable
      leukocytes and erythrocyte count. Additional settings offered by the instrument
      may be useful in the diagnosis of neurological disorders.

PMID- 11238313
TI  - Homogeneous enzyme immunoassay for triiodothyronine in serum.
AB  - BACKGROUND: The concentration of triiodothyronine (T3) in human serum is
      extremely low and can be determined only by very sensitive methods. We developed
      a homogeneous enzyme immunoassay for T3 analysis in unextracted serum. METHODS: A
      T(3) derivative was conjugated to the -SH groups of glycogen phosphorylase b
      (GPb) from rabbit muscle. Conjugation caused inhibition of enzyme activity, and
      the enzyme conjugate was reactivated upon binding of anti-T3 antibody. Activation
      was blocked by the presence of non-antibody-bound T3; this was the basis for the
      development of the homogeneous enzyme immunoassay for T3 by determining GPb
      activity fluorometrically. RESULTS: We used furosemide to block the interaction
      of T3 with serum proteins with T3-binding sites, avoiding any serum treatment
      step. T3 was measured in the range 0.3-8 microg/L. T3 values obtained by this
      assay correlated well with those obtained by a RIA (y = 0.97x - 0.07 microg/L; r
      = 0.96; n = 92). Within- and between-run imprecision (CV) was 5-9% for normal and
      high concentrations and 16-20% for low concentrations. CONCLUSIONS: Chemical
      modification of GPb with a T3 derivative allows the development of a simple
      homogeneous enzyme immunoassay for T3 in unextracted serum.

PMID- 11238312
TI  - Europium nanoparticles and time-resolved fluorescence for ultrasensitive
      detection of prostate-specific antigen.
AB  - BACKGROUND: Nanoparticle-based detection technologies have the potential to
      improve detection sensitivity in miniature as well as in conventional biochemical
      assays. We introduce a detection technology that relies on the use of
      europium(III) nanoparticles and time-resolved fluorometry to improve the
      detection limit of biochemical assays and to visualize individual molecules in a
      microtiter plate format. METHODS: Streptavidin was covalently coated on 107-nm
      nanoparticles containing >30 000 europium molecules entrapped with beta
      diketones. In a model assay system, these nanoparticles were used to trace
      biotinylated prostate-specific antigen (PSA) in a microtiter plate format.
      RESULTS: The detection limit (mean + 3 SD of the zero calibrator) of biotinylated
      PSA was 0.38 ng/L, corresponding to 10 fmol/L or 60 zeptomoles (60 x 10(-21)
      moles) of PSA. Moreover, single nanoparticles, representing individual PSA
      molecules, were visualized in the same microtiter wells with a time-resolved
      fluorescence microscope using a x10 objective. Single nanoparticles, possessing
      high specific activity, were also detected in solution by a standard time
      resolved plate fluorometer. CONCLUSIONS: The universal streptavidin-coated
      europium(III) nanoparticle label is suitable for detection of any biotinylated
      molecule either in solution or on a solid phase. The europium(III) nanoparticle
      labeling technology is applicable to many areas of modern biochemical analysis,
      such as immunochemical and multianalyte DNA-chip assays as well as histo- and
      cytochemistry to improve detection sensitivities.

PMID- 11238314
TI  - Year-long validation study and reference values for urinary amino acids using a
      reversed-phase HPLC method.
AB  - BACKGROUND: Reversed-phase HPLC (RP-HPLC) has become an alternative to ion
      exchange chromatography for amino acid analysis in biological fluids. However,
      validation studies for its urine application are limited, and the corresponding
      reference values have not been reported extensively. We studied the long-term
      performance of a commercial HPLC method for urine amino acid analysis and
      established specific age-related reference values for urine amino acid excretion.
      METHODS: Method performance was continuously assessed by recovery and precision
      studies with urine samples and controls, respectively. Healthy individuals were
      prospectively analyzed throughout a 5-year period. Excretion of individual amino
      acids, expressed as mmol/mol of creatinine, was included in six age-related
      groups for random urine samples (0-1 month, 1-12 months, 1-3 years, 3-8 years, 8
      16 years, and >16 years) and in two groups for 24-h urine collections (8-16 years
      and >16 years). RESULTS: Over a 1-year period, CVs for retention times were <0.5%
      and 3.3% for within- and between-run imprecision, respectively. For amino acid
      concentrations, within-run CVs were 2.9-17% and between-run CVs were 7.1-46% for
      the same period. Amino acid recoveries were 78-122%. Reference intervals for 35
      amino acids were calculated and compared with the concentrations observed in
      patients diagnosed with specific pathologies. A few statistically significant
      differences were found between the reference intervals derived using random and
      24-h urine collections. CONCLUSIONS: Long-term reliability of the RP-HPLC method
      for urine amino acid analysis has been demonstrated. Representative age-related
      reference intervals for the RP-HPLC method in both random urine and 24-h urine
      collections have been established, and their feasibility for diagnosis of
      aminoaciduria has been shown. These intervals could serve as a guide for
      laboratories changing to HPLC methods.

PMID- 11238315
TI  - Evaluation of a new, rapid bedside test for quantitative determination of B-type
      natriuretic peptide.

PMID- 11238317
TI  - International survey on the use of cardiac markers.

PMID- 11238316
TI  - Creatine kinase MB, troponin I, and troponin T release patterns after coronary
      artery bypass grafting with or without cardiopulmonary bypass and after aortic
      and mitral valve surgery.

PMID- 11238318
TI  - Laboratory-based calculation of coronary heart disease risk.

PMID- 11238320
TI  - Measurement of low apolipoprotein concentrations by optimized immunoturbidimetric
      applications.

PMID- 11238322
TI  - Comparative study of liquid-liquid extraction and solid-phase extraction methods
      for the separation of sufentanil from plasma before gas chromatographic-mass
      spectrometric analysis.

PMID- 11238321
TI  - Serum tartrate-resistant acid phosphatase 5b is a specific and sensitive marker
      of bone resorption.

PMID- 11238323
TI  - Elecsys insulin assay: free insulin determination and the absence of cross
      reactivity with insulin lispro.

PMID- 11238324
TI  - How accurate are references in clinical chemistry?

PMID- 11238325
TI  - Prostaglandin D synthase does not produce prostate-specific antigen cross
      reactivity in renal cell carcinoma.

PMID- 11238326
TI  - Plasma cardiac troponin concentrations after extreme exercise.

PMID- 11238331
TI  - Is it acceptable to discharge a heroin user with an intravenous line to complete
      his antibiotic therapy for cellulitis at home under a nurse's supervision? Yes:
      supervised home care ensures continued treatment at lower cost.

PMID- 11238332
TI  - Is it acceptable to discharge a heroin user with an intravenous line to complete
      his antibiotic therapy for cellulitis at home under a nurse's supervision? No: a
      home central line is too hazardous.

PMID- 11238333
TI  - How to practice evidence-based pediatrics.

PMID- 11238335
TI  - A new law to improve pain management and end-of-life care: learning how to treat
      patients in pain and near death must become a priority.

PMID- 11238337
TI  - US web site will publish list of "drug-free practitioners".

PMID- 11238338
TI  - Spider venom may prevent atrial fibrillation.

PMID- 11238339
TI  - CNA to hold town hall meetings on nurse ratio proposal.

PMID- 11238342
TI  - Severe caries in a child.

PMID- 11238345
TI  - Hospital overcrowding.

PMID- 11238343
TI  - Troublesome inconsistencies in the federal regulation of pyrethrin-based
      shampoos.

PMID- 11238347
TI  - What are the goals of patient education?

PMID- 11238348
TI  - A descriptive study of managed-care hassles in 26 practices.
AB  - OBJECTIVES: To explore the nature of managed-care hassles in primary care
      physicians' offices and to determine the feasibility of practice-based research
      methods to study the problem. METHODS: 16 internists and 10 family physicians
      volunteered to collect data about managed-care hassles during or shortly after
      the office visit for 15 consecutive patients using preprinted data cards. Outcome
      measures Number of hassles, time required for hassles, and interference with
      quality of care and doctor-patient relationship. RESULTS: Physicians adapted
      easily to using data cards. Before the pilot study, participants estimated a
      hassle rate of 10% and thought that interference with quality of care and the
      doctor-patient relationship was infrequent. Of 376 total visits for which the
      physicians completed data cards, 23% of visits generated 1 or more hassles. On
      average, a physician who saw 22 patients daily experienced 1 hassle lasting 10
      minutes for every 4 to 5 patients. More than 40% of hassles were reported as
      interfering with quality of care, the doctor-patient relationship, or both.
      CONCLUSIONS: The high hassle rate, in addition to the interference of hassles
      with quality of care and the doctor-patient relationship, suggests the need for
      further investigation into managed-care hassles using practice-based research
      methods.

PMID- 11238350
TI  - Resident overnight call--an idea past its time?

PMID- 11238353
TI  - How to assess new treatments.

PMID- 11238354
TI  - "What do we tell the children?": understanding childhood grief.

PMID- 11238356
TI  - Is the MMR vaccine safe?

PMID- 11238360
TI  - Complementary medicine use by Mexican migrants in the San Francisco Bay Area.

PMID- 11238362
TI  - Myth: corneal abrasions require routine patching.

PMID- 11238363
TI  - Japanese Americans and self-care: a lesson in cross-cultural care.

PMID- 11238364
TI  - Rural elders and long-term care.

PMID- 11238367
TI  - Call for help.

PMID- 11238369
TI  - Listening (for what is not said).

PMID- 11238371
TI  - RNA interference--2001.

PMID- 11238372
TI  - Fine structure of E. coli RNA polymerase-promoter interactions: alpha subunit
      binding to the UP element minor groove.
AB  - The alpha subunit of E. coli RNAP plays an important role in the recognition of
      many promoters by binding to the A+T-rich UP element, a DNA sequence located
      upstream of the recognition elements for the sigma subunit, the -35 and -10
      hexamers. We examined DNA-RNAP interactions using high resolution interference
      and protection footprinting methods and using the minor groove-binding drug
      distamycin. Our results suggest that alpha interacts with bases in the DNA minor
      groove and with the DNA backbone along the minor groove, but that UP element
      major groove surfaces do not make a significant contribution to alpha binding. On
      the basis of these and previous results, we propose a model in which alpha
      contacts UP element DNA through amino acid residues located in a pair of helix
      hairpin-helix motifs. Furthermore, our experiments extend existing information
      about recognition of the core promoter by sigma(70) by identifying functional
      groups in the major grooves of the -35 and -10 hexamers in which modifications
      interfere with RNAP binding. These studies greatly improve the resolution of our
      picture of the promoter-RNAP interaction.

PMID- 11238373
TI  - A multistep damage recognition mechanism for global genomic nucleotide excision
      repair.
AB  - A mammalian nucleotide excision repair (NER) factor, the XPC-HR23B complex, can
      specifically bind to certain DNA lesions and initiate the cell-free repair
      reaction. Here we describe a detailed analysis of its binding specificity using
      various DNA substrates, each containing a single defined lesion. A highly
      sensitive gel mobility shift assay revealed that XPC-HR23B specifically binds a
      small bubble structure with or without damaged bases, whereas dual incision takes
      place only when damage is present in the bubble. This is evidence that damage
      recognition for NER is accomplished through at least two steps; XPC-HR23B first
      binds to a site that has a DNA helix distortion, and then the presence of injured
      bases is verified prior to dual incision. Cyclobutane pyrimidine dimers (CPDs)
      were hardly recognized by XPC-HR23B, suggesting that additional factors may be
      required for CPD recognition. Although the presence of mismatched bases opposite
      a CPD potentiated XPC-HR23B binding, probably due to enhancement of the helix
      distortion, cell-free excision of such compound lesions was much more efficient
      than expected from the observed affinity for XPC-HR23B. This also suggests that
      additional factors and steps are required for the recognition of some types of
      lesions. A multistep mechanism of this sort may provide a molecular basis for
      ensuring the high level of damage discrimination that is required for global
      genomic NER.

PMID- 11238374
TI  - C. elegans mre-11 is required for meiotic recombination and DNA repair but is
      dispensable for the meiotic G(2) DNA damage checkpoint.
AB  - We investigated the roles of Caenorhabditis elegans MRE-11 in multiple cellular
      processes required to maintain genome integrity. Although yeast Mre11 is known to
      promote genome stability through several diverse pathways, inviability of
      vertebrate cells that lack Mre11 has hindered elucidation of the in vivo roles of
      this conserved protein in metazoan biology. Worms homozygous for an mre-11 null
      mutation are viable, allowing us to demonstrate in vivo requirements for MRE-11
      in meiotic recombination and DNA repair. In mre-11 mutants, meiotic crossovers
      are not detected, and oocyte chromosomes lack chiasmata but appear otherwise
      intact. gamma-irradiation of mre-11 mutant germ cells during meiotic prophase
      eliminates progeny survivorship and induces chromosome fragmentation and other
      cytologically visible abnormalities, indicating a defect in repair of radiation
      induced chromosome damage. Whereas mre-11 mutant germ cells are repair-deficient,
      they retain function of the meiotic G(2) DNA damage checkpoint that triggers germ
      cell apoptosis in response to ionizing radiation. Although mre-11/mre-11 animals
      derived from heterozygous parents are viable and produce many embryos, there is a
      marked drop both in the number and survivorship of embryos produced by succeeding
      generations. This progressive loss of fecundity and viability indicates that MRE
      11 performs a function essential for maintaining reproductive capacity in the
      species.

PMID- 11238376
TI  - Ataxia telangiectasia mutated is essential during adult neurogenesis.
AB  - Ataxia telangiectasia (A-T) is an autosomal recessive disease characterized by
      normal brain development followed by progressive neurodegeneration. The gene
      mutated in A-T (ATM) is a serine protein kinase implicated in cell cycle
      regulation and DNA repair. The role of ATM in the brain and the consequences of
      its loss on neuronal survival remain unclear. We studied the role of ATM in adult
      neural progenitor cells in vivo and in vitro to define the role of ATM in
      dividing and postmitotic neural cells from Atm-deficient (Atm(-/-)) mice in a
      physiologic context. We demonstrate that ATM is an abundant protein in dividing
      neural progenitor cells but is markedly down-regulated as cells differentiate. In
      the absence of ATM, neural progenitor cells of the dentate gyrus show abnormally
      high rates of proliferation and genomic instability. Atm(-/-) cells in vivo, and
      in cell culture, show a blunted response to environmental stimuli that promote
      neural progenitor cell proliferation, survival, and differentiation along a
      neuronal lineage. This study defines a role for ATM during the process of
      neurogenesis, demonstrates that ATM is required for normal cell fate
      determination and neuronal survival both in vitro and in vivo, and points to a
      mechanism for neuronal cell loss in progressive neurodegenerative diseases.

PMID- 11238377
TI  - Krox-20 patterns the hindbrain through both cell-autonomous and non cell
      autonomous mechanisms.
AB  - The Krox-20 gene encodes a zinc finger transcription factor, which has been shown
      previously, by targeted inactivation in the mouse, to be required for the
      development of rhombomeres (r) 3 and 5 in the segmented embryonic hindbrain. In
      the present work, Krox-20 was expressed ectopically in the developing chick
      hindbrain by use of electroporation. We demonstrate that Krox-20 expression is
      sufficient to confer odd-numbered rhombomere characteristics to r2, r4, and r6
      cells, presumably in a cell-autonomous manner. Therefore, Krox-20, appears as the
      major determinant of odd-numbered identity within the hindbrain. In addition, we
      provide evidence for the existence of a non cell-autonomous autoactivation
      mechanism allowing recruitment of Krox-20-positive cells from even-numbered
      territories by neighboring Krox-20-expressing cells. On the basis of these
      observations, we propose that Krox-20 regulates multiple, intertwined steps in
      segmental patterning: Initial activation of Krox-20 in a few cells leads to the
      segregation, homogenization, and possibly expansion of territories to which Krox
      20 in addition confers an odd-numbered identity.

PMID- 11238375
TI  - Regulation of gene expression by the small GTPase Rho through the ERK6 (p38
      gamma) MAP kinase pathway.
AB  - Small GTP-binding proteins of the Rho-family, Rho, Rac, and Cdc42, have been
      traditionally linked to the regulation of the cellular actin-based cytoskeleton.
      Rac and Cdc42 can also control the activity of JNK, thus acting in a molecular
      pathway transmitting extracellular signals to the nucleus. Interestingly, Rho can
      also regulate gene expression, albeit by a not fully understood mechanism. Here,
      we found that activated RhoA can stimulate c-jun expression and the activity of
      the c-jun promoter. As the complexity of the signaling pathways controlling the
      expression of c-jun has begun to be unraveled, this finding provided a unique
      opportunity to elucidate the biochemical routes whereby RhoA regulates nuclear
      events. We found that RhoA can initiate a linear kinase cascade leading to the
      activation of ERK6 (p38 gamma), a recently identified member of the p38 family of
      MAPKs. Furthermore, we present evidence that RhoA, PKN, MKK3/MKK6, and ERK6 (p38
      gamma) are components of a novel signal transduction pathway involved in the
      regulation of gene expression and cellular transformation.

PMID- 11238378
TI  - KNOX homeodomain protein directly suppresses the expression of a gibberellin
      biosynthetic gene in the tobacco shoot apical meristem.
AB  - To identify genes targeted by the tobacco KNOX homeodomain protein, Nicotiana
      tabacum homeobox 15 (NTH15), we have generated an inducible system using the
      human glucocorticoid receptor. In this system, steroid treatment strictly induced
      NTH15 function and immediately suppressed the expression of a gibberellin (GA)
      biosynthetic gene encoding GA 20-oxidase (Ntc12) and also resulted in a decrease
      in bioactive GA levels. The repression of Ntc12 was observed even when indirect
      effects were blocked by cycloheximide. NTH15 mRNA was present in corpus cells of
      the shoot apical meristem (SAM), whereas Ntc12 mRNA was observed in leaf
      primordia and rib meristem but not in the corpus. Recombinant NTH15 protein
      strongly bound to a 5-bp dyadsymmetric sequence, GTGAC, in the first intron of
      Ntc12 in vitro. Mutation of this sequence in the Ntc12 gene abolished the NTH15
      dependent suppression of Ntc12 in the corpus of the SAM. Our results indicate
      that NTH15 directly represses Ntc12 expression in the corpus of the wild-type SAM
      to maintain the indeterminate state of corpus cells. The suppression of NTH15
      within cells at the flanks of the SAM permits GA biosynthesis, which promotes
      organized cell proliferation and consequently induces the determination of cell
      fate.

PMID- 11238379
TI  - Robertson's Mutator transposons in A. thaliana are regulated by the chromatin
      remodeling gene Decrease in DNA Methylation (DDM1).
AB  - Robertson's Mutator transposable elements in maize undergo cycles of activity and
      then inactivity that correlate with changes in cytosine methylation. Mutator-like
      elements are present in the Arabidopsis genome but are heavily methylated and
      inactive. These elements become demethylated and active in the chromatin
      remodeling mutant ddm1 (Decrease in DNA Methylation), which leads to loss of
      heterochromatic DNA methylation. Thus, DNA transposons in plants appear to be
      regulated by chromatin remodeling. In inbred ddm1 strains, transposed elements
      may account, in part, for mutant phenotypes unlinked to ddm1. Gene silencing and
      paramutation are also regulated by DDM1, providing support for the proposition
      that epigenetic silencing is related to transposon regulation.

PMID- 11238381
TI  - In vivo chromatin remodeling by yeast ISWI homologs Isw1p and Isw2p.
AB  - Isw1p and Isw2p are budding yeast homologs of the Drosophila ISWI chromatin
      remodeling ATPase. Using indirect-end-label and chromatin immunoprecipitation
      analysis, we show both independent and cooperative Isw1p- and Isw2p-mediated
      positioning of short nucleosome arrays in gene-regulatory elements at a variety
      of transcription units in vivo. We present evidence that both yeast ISWI
      complexes regulate developmental responses to starvation and that for Isw2p,
      recruitment by different DNA-binding proteins controls meiosis and haploid
      invasive growth.

PMID- 11238380
TI  - Purification and characterization of mSin3A-containing Brg1 and hBrm chromatin
      remodeling complexes.
AB  - Alteration of nucleosomes by ATP-dependent remodeling complexes represents a
      critical step in the regulation of transcription. The human SWI/SNF (hSWI/SNF)
      family is composed of complexes that contain either Brg1 or hBrm as the central
      ATPase; however, these separate complexes have not been compared functionally.
      Here we describe the establishment of cell lines that express epitope-tagged Brg1
      and hBrm and a characterization of the complexes associated with these two
      ATPases. We show that Brg1 fractionates into two complexes that differ in
      activity and subunit composition, whereas hBrm is found in one complex with lower
      activity than the Brg1 complexes. These three complexes can remodel nucleosomal
      arrays, increase restriction enzyme accessibility, and hydrolyze ATP in a DNA
      dependent manner. The three complexes differ markedly in their ability to remodel
      mononucleosomal core particles. We also show that the hBrm complex and one of the
      Brg1 complexes contain components of the mammalian Sin3 (mSin3) complex. In
      addition, we have found that Brg1, hBrm, and BAF155 can interact specifically
      with mSin3A in vitro, showing a direct association of hSWI/SNF complexes with
      proteins involved in gene repression. These unexpected functional characteristics
      indicate that these hSWI/SNF complexes play diverse regulatory roles.

PMID- 11238383
TI  - Memories of a mentor: Charley Steinberg.

PMID- 11238382
TI  - The RssB response regulator directly targets sigma(S) for degradation by ClpXP.
AB  - The sigma(S) subunit of Escherichia coli RNA polymerase regulates the expression
      of stationary phase and stress response genes. Control over sigma(S) activity is
      exercised in part by regulated degradation of sigma(S). In vivo, degradation
      requires the ClpXP protease together with RssB, a protein homologous to response
      regulator proteins. Using purified components, we reconstructed the degradation
      of sigma(S) in vitro and demonstrate a direct role for RssB in delivering
      sigma(S) to ClpXP. RssB greatly stimulates sigma(S) degradation by ClpXP. Acetyl
      phosphate, which phosphorylates RssB, is required. RssB participates in multiple
      rounds of sigma(S) degradation, demonstrating its catalytic role. RssB promotes
      sigma(S) degradation specifically; it does not affect degradation of other ClpXP
      substrates or other proteins not normally degraded by ClpXP. sigma(S) and RssB
      form a stable complex in the presence of acetyl phosphate, and together they form
      a ternary complex with ClpX that is stabilized by ATP[gamma-S]. Alone, neither
      sigma(S) nor RssB binds ClpX with high affinity. When ClpP is present, a larger
      sigma(S)--RssB--ClpXP complex forms. The complex degrades sigma(S) and releases
      RssB from ClpXP in an ATP-dependent reaction. Our results illuminate an important
      mechanism for regulated protein turnover in which a unique targeting protein,
      whose own activity is regulated through specific signaling pathways, catalyzes
      the delivery of a specific substrate to a specific protease.

PMID- 11238384
TI  - Identification of virulence mutants of the fungal pathogen Cryptococcus
      neoformans using signature-tagged mutagenesis.
AB  - Cryptococcus neoformans var. neoformans is an important opportunistic fungal
      pathogen of patients whose immune system has been compromised due to viral
      infection, antineoplastic chemotherapy, or tissue transplantation. As many as 13%
      of all AIDS patients suffer a life-threatening cryptococcal infection at some
      time during the course of their HIV disease. To begin to understand the molecular
      basis for virulence in Cryptococcus neoformans var. neoformans serotype A, we
      have employed signature-tagged mutagenesis (STM) to identify mutants with altered
      virulence in a mouse model. The critical parameters of signature-tagged
      mutagenesis in C. neoformans are explored. Data are presented showing that at
      least 100 different strains can be mixed together in a single animal with each
      participating in the infection and that there is no apparent interaction between
      a virulent strain and an avirulent strain in our animal model. Using signature
      tagged mutagenesis, we identified 39 mutants with significantly altered growth in
      a competitive assay. Molecular analyses of these mutants indicated that 19 (49%)
      contained an insertion in the actin promoter by homologous recombination from a
      single crossover event, creating a duplication of the actin promoter and the
      integration of single or multiple copies of the vector. Analysis of the
      chromosomal insertion sites of those mutants that did not have an integration
      event in the actin promoter revealed an approximately random distribution among
      the chromosomes. Individual challenge of the putative mutants in a mouse model
      revealed five hypovirulent mutants and one hypervirulent mutant.

PMID- 11238385
TI  - Mapping of avirulence genes in Phytophthora infestans with amplified fragment
      length polymorphism markers selected by bulked segregant analysis.
AB  - In this study we investigated the genetic control of avirulence in the diploid
      oomycete pathogen Phytophthora infestans, the causal agent of late blight on
      potato. The dominant avirulence (Avr) genes matched six race-specific resistance
      genes introgressed in potato from a wild Solanum species. AFLP markers linked to
      Avr genes were selected by bulked segregant analysis and used to construct two
      high-density linkage maps, one containing Avr4 (located on linkage group A2-a)
      and the other containing a cluster of three tightly linked genes, Avr3, Avr10,
      and Avr11 (located on linkage group VIII). Bulked segregant analysis also
      resulted in a marker linked to Avr1 and this allowed positioning of Avr1 on
      linkage group IV. No bulked segregant analysis was performed for Avr2, but
      linkage to a set of random markers placed Avr2 on linkage group VI. Of the six
      Avr genes, five were located on the most distal part of the linkage group,
      possibly close to the telomere. The high-density mapping was initiated to
      facilitate future positional cloning of P. infestans Avr genes.

PMID- 11238386
TI  - Accumulation of stress and inducer-dependent plant-cell-wall-degrading enzymes
      during asexual development in Aspergillus nidulans.
AB  - Determination and interpretation of fungal gene expression profiles based on
      digital reconstruction of expressed sequenced tags (ESTs) are reported. A total
      of 51,524 DNA sequence files processed with PipeOnline resulted in 9775 single
      and 5660 contig unique ESTs, 31.2% of a typical fungal transcriptome. Half of the
      unique ESTs shared homology with genes in public databases, 35.8% of which are
      functionally defined and 64.2% are unclear or unknown. In Aspergillus nidulans
      86% of transcripts associate with intermediate metabolism functions, mainly
      related to carbohydrate, amino acid, protein, and peptide biosynthesis. During
      asexual development, A. nidulans unexpectedly accumulates stress response and
      inducer-dependent transcripts in the absence of an inducer. Stress response genes
      in A. nidulans ESTs total 1039 transcripts, contrasting with 117 in Neurospora
      crassa, a 14.3-fold difference. A total of 5.6% of A. nidulans ESTs implicate
      inducer-dependent cell wall degradation or amino acid acquisition, 3.5-fold
      higher than in N. crassa. Accumulation of stress response and inducer-dependent
      transcripts suggests general derepression of cis-regulation during terminal
      asexual development.

PMID- 11238387
TI  - Characterization of the Aspergillus nidulans septin (asp) gene family.
AB  - Members of the septin gene family are involved in cytokinesis and the
      organization of new growth in organisms as diverse as yeast, fruit fly, worm,
      mouse, and human. Five septin genes have been cloned and sequenced from the model
      filamentous fungus A. nidulans. As expected, the A. nidulans septins contain the
      highly conserved GTP binding and coiled-coil domains seen in other septins. On
      the basis of hybridization of clones to a chromosome-specific library and
      correlation with an A. nidulans physical map, the septins are not clustered but
      are scattered throughout the genome. In phylogenetic analysis most fungal septins
      could be grouped with one of the prototypical S. cerevisiae septins, Cdc3, Cdc10,
      Cdc11, and Cdc12. Intron-exon structure was conserved within septin classes. The
      results of this study suggest that most fungal septins belong to one of four
      orthologous classes.

PMID- 11238388
TI  - The Neurospora crassa genome: cosmid libraries sorted by chromosome.
AB  - A Neurospora crassa cosmid library of 12,000 clones (at least nine genome
      equivalents) has been created using an improved cosmid vector pLorist6Xh, which
      contains a bacteriophage lambda origin of replication for low-copy-number
      replication in bacteria and the hygromycin phosphotransferase marker for direct
      selection in fungi. The electrophoretic karyotype of the seven chromosomes
      comprising the 42.9-Mb N. crassa genome was resolved using two translocation
      strains. Using gel-purified chromosomal DNAs as probes against the new cosmid
      library and the commonly used medium-copy-number pMOcosX N. crassa cosmid library
      in two independent screenings, the cosmids were assigned to chromosomes.
      Assignments of cosmids to linkage groups on the basis of the genetic map vs. the
      electrophoretic karyotype are 93 +/- 3% concordant. The size of each chromosome
      specific subcollection of cosmids was found to be linearly proportional to the
      size of the particular chromosome. Sequencing of an entire cosmid containing the
      qa gene cluster indicated a gene density of 1 gene per 4 kbp; by extrapolation,
      11,000 genes would be expected to be present in the N. crassa genome. By
      hybridizing 79 nonoverlapping cosmids with an average insert size of 34 kbp
      against cDNA arrays, the density of previously characterized expressed sequence
      tags (ESTs) was found to be slightly <1 per cosmid (i.e., 1 per 40 kbp), and most
      cosmids, on average, contained an identified N. crassa gene sequence as a
      starting point for gene identification.

PMID- 11238389
TI  - The ste3 pheromone receptor gene of Pneumocystis carinii is surrounded by a
      cluster of signal transduction genes.
AB  - Although the clinical aspects of Pneumocystis carinii pneumonia are well
      characterized, the basic biology of the causative organism is poorly understood.
      Most proposed life cycles of P. carinii include both asexual and sexual
      replicative cycles. The two most prominent morphological forms are a trophic
      form, thought to undergo asexual replication by binary fission, and a cystic form
      or ascus containing intracystic bodies or ascospores, the products of sexual
      replication. To facilitate the Pneumocystis genome project, a P. carinii f. sp.
      carinii genomic cosmid library and an additional lambda cDNA library were
      generated. A partial expressed sequence tag database, created as part of the
      genome project, revealed the transcription of meiosis-specific genes and other
      genes related to sexual reproduction. The ortholog of Ste3, an a-factor pheromone
      receptor, was cloned and genes surrounding the ste3 locus were examined.
      Clustered around the ste3 gene are genes encoding elements functional in the
      pheromone response signal transduction cascade of model fungal organisms. These
      include the Ste20 protein kinase, the Ste12 homoeodomain transcriptional
      regulator, a potential pheromone mating factor, and other DNA-binding proteins.
      The genomic organization of the ste3 locus bears significant similarity to that
      of the mating locus recently described in Cryptococcus neoformans. The P. carinii
      genome contains much of the genetic machinery necessary for pheromone
      responsiveness, and these data support the existence of a sexual replication
      cycle.

PMID- 11238390
TI  - An STE12 homolog from the asexual, dimorphic fungus Penicillium marneffei
      complements the defect in sexual development of an Aspergillus nidulans steA
      mutant.
AB  - Penicillium marneffei is an opportunistic fungal pathogen of humans and the only
      dimorphic species identified in its genus. At 25 degrees P. marneffei exhibits
      true filamentous growth, while at 37 degrees P. marneffei undergoes a dimorphic
      transition to produce uninucleate yeast cells that divide by fission. Members of
      the STE12 family of regulators are involved in controlling mating and yeast
      hyphal transitions in a number of fungi. We have cloned a homolog of the S.
      cerevisiae STE12 gene from P. marneffei, stlA, which is highly conserved. The
      stlA gene, along with the A. nidulans steA and Cryptococcus neoformans STE12alpha
      genes, form a distinct subclass of STE12 homologs that have a C2H2 zinc-finger
      motif in addition to the homeobox domain that defines STE12 genes. To examine the
      function of stlA in P. marneffei, we isolated a number of mutants in the P.
      marneffei-type strain and, in combination with selectable markers, developed a
      highly efficient DNA-mediated transformation procedure and gene deletion
      strategy. Deletion of the stlA gene had no detectable effect on vegetative
      growth, asexual development, or dimorphic switching in P. marneffei. Despite the
      lack of a detectable function, the P. marneffei stlA gene complemented the sexual
      defect of an A. nidulans steA mutant. In addition, substitution rate estimates
      indicate that there is a significant bias against nonsynonymous substitutions.
      These data suggest that P. marneffei may have a previously unidentified cryptic
      sexual cycle.

PMID- 11238391
TI  - Hybridization-based mapping of Neurospora crassa linkage groups II and V.
AB  - As part of the German Neurospora crassa genome project, physical clone maps of
      linkage groups II and V of N. crassa were generated by hybridization-based
      mapping. To this end, two different types of clone library were used: (1) a
      bacterial artificial clone library of 15-fold genome coverage and an average
      insert size of 69 kb, and (2) three cosmid libraries--each cloned in a different
      vector--with 17-fold coverage and 34 kb average insert size. For analysis, the
      libraries were arrayed on filters. At the first stage, chromosome-specific
      sublibraries were selected by hybridization of the respective chromosomal DNA
      fragments isolated from pulsed-field electrophoresis gels. Subsequently, the
      sublibraries were exhaustively ordered by single clone hybridizations.
      Eventually, the global libraries were used again for gap filling. By this means,
      physical maps were generated that consist of 13 and 21 contigs, respectively, and
      form the basis of the current sequencing effort on the two chromosomes.

PMID- 11238392
TI  - Parallel computation of a maximum-likelihood estimator of a physical map.
AB  - Reconstructing a physical map of a chromosome from a genomic library presents a
      central computational problem in genetics. Physical map reconstruction in the
      presence of errors is a problem of high computational complexity that provides
      the motivation for parallel computing. Parallelization strategies for a maximum
      likelihood estimation-based approach to physical map reconstruction are
      presented. The estimation procedure entails a gradient descent search for
      determining the optimal spacings between probes for a given probe ordering. The
      optimal probe ordering is determined using a stochastic optimization algorithm
      such as simulated annealing or microcanonical annealing. A two-level
      parallelization strategy is proposed wherein the gradient descent search is
      parallelized at the lower level and the stochastic optimization algorithm is
      simultaneously parallelized at the higher level. Implementation and experimental
      results on a distributed-memory multiprocessor cluster running the parallel
      virtual machine (PVM) environment are presented using simulated and real
      hybridization data.

PMID- 11238393
TI  - ODS2: a multiplatform software application for creating integrated physical and
      genetic maps.
AB  - A contig map is a physical map that shows the native order of a library of
      overlapping genomic clones. One common method for creating such maps involves
      using hybridization to detect clone overlaps. False- positive and false-negative
      hybridization errors, the presence of chimeric clones, and gaps in library
      coverage lead to ambiguity and error in the clone order. Genomes with good
      genetic maps, such as Neurospora crassa, provide a means for reducing ambiguities
      and errors when constructing contig maps if clones can be anchored with genetic
      markers to the genetic map. A software application called ODS2 for creating
      contig maps based on clone-clone hybridization data is presented. This
      application is also designed to exploit partial ordering information provided by
      anchorage of clones to a genetic map. This information, along with clone-clone
      hybridization data, is used by a clone ordering algorithm and is represented
      graphically, allowing users to interactively align physical and genetic maps.
      ODS2 has a graphical user interface and is implemented entirely in Java, so it
      runs on multiple platforms. Other features include the flexibility of storing
      data in a local file or relational database and the ability to create full or
      minimum tiling contig maps.

PMID- 11238394
TI  - Analysis of expressed sequence tags from two starvation, time-of-day-specific
      libraries of Neurospora crassa reveals novel clock-controlled genes.
AB  - In an effort to determine genes that are expressed in mycelial cultures of
      Neurospora crassa over the course of the circadian day, we have sequenced 13,000
      cDNA clones from two time-of-day-specific libraries (morning and evening library)
      generating approximately 20,000 sequences. Contig analysis allowed the
      identification of 445 unique expressed sequence tags (ESTs) and 986 ESTs present
      in multiple cDNA clones. For approximately 50% of the sequences (710 of 1431),
      significant matches to sequences in the National Center for Biotechnology
      Information database (of known or unknown function) were detected. About 50% of
      the ESTs (721 of 1431) showed no similarity to previously identified genes. We
      hybridized Northern blots with probes derived from 26 clones chosen from contigs
      identified by multiple cDNA clones and EST sequences. Using these sequences, the
      representation of genes among the morning and evening sequences, respectively, in
      most cases does not reflect their expression patterns over the course of the day.
      Nevertheless, we were able to identify four new clock-controlled genes. On the
      basis of these data we predict that a significant proportion of the expressed
      Neurospora genes may be regulated by the circadian clock. The mRNA levels of all
      four genes peak in the subjective morning as is the case with previously
      identified ccgs.

PMID- 11238395
TI  - Analysis of the pdx-1 (snz-1/sno-1) region of the Neurospora crassa genome:
      correlation of pyridoxine-requiring phenotypes with mutations in two structural
      genes.
AB  - We report the analysis of a 36-kbp region of the Neurospora crassa genome, which
      contains homologs of two closely linked stationary phase genes, SNZ1 and SNO1,
      from Saccharomyces cerevisiae. Homologs of SNZ1 encode extremely highly conserved
      proteins that have been implicated in pyridoxine (vitamin B6) metabolism in the
      filamentous fungi Cercospora nicotianae and in Aspergillus nidulans. In N.
      crassa, SNZ and SNO homologs map to the region occupied by pdx-1 (pyridoxine
      requiring), a gene that has been known for several decades, but which was not
      sequenced previously. In this study, pyridoxine-requiring mutants of N. crassa
      were found to possess mutations that disrupt conserved regions in either the SNZ
      or SNO homolog. Previously, nearly all of these mutants were classified as pdx-1.
      However, one mutant with a disrupted SNO homolog was at one time designated pdx
      2. It now appears appropriate to reserve the pdx-1 designation for the N. crassa
      SNZ homolog and pdx-2 for the SNO homolog. We further report annotation of the
      entire 36,030-bp region, which contains at least 12 protein coding genes,
      supporting a previous conclusion of high gene densities (12,000-13,000 total
      genes) for N. crassa. Among genes in this region other than SNZ and SNO homologs,
      there was no evidence of shared function. Four of the genes in this region appear
      to have been lost from the S. cerevisiae lineage.

PMID- 11238396
TI  - Two types of recombination hotspots in bacteriophage T4: one requires DNA damage
      and a replication origin and the other does not.
AB  - Recombination hotspots have previously been discovered in bacteriophage T4 by two
      different approaches, marker rescue recombination from heavily damaged phage
      genomes and recombination during co-infection by two undamaged phage genomes. The
      phage replication origin ori(34) is located in a region that has a hotspot in
      both assays. To determine the relationship between the origin and the two kinds
      of hotspots, we generated phage carrying point mutations that should inactivate
      ori(34) but not affect the gene 34 reading frame (within which ori(34) is
      located). The mutations eliminated the function of the origin, as judged by both
      autonomous replication of plasmids during T4 infection and two-dimensional gel
      analysis of phage genomic replication intermediates. As expected from past
      studies, the ori(34) mutations also eliminated the hotspot for marker rescue
      recombination from UV-irradiated genomes. However, the origin mutations had no
      effect on the recombination hotspot that is observed with co-infecting undamaged
      phage genomes, demonstrating that some DNA sequence other than the origin is
      responsible for inflated recombination between undamaged genomes. The hotspots
      for marker rescue recombination may result from a replication fork restart
      process that acts upon origin-initiated replication forks that become blocked at
      nearby DNA damage. The two-dimensional gel analysis also revealed phage T4
      replication intermediates not previously detected by this method, including
      origin theta forms.

PMID- 11238397
TI  - Mutations in the YRB1 gene encoding yeast ran-binding-protein-1 that impair
      nucleocytoplasmic transport and suppress yeast mating defects.
AB  - We identified two temperature-sensitive (ts) mutations in the essential gene,
      YRB1, which encodes the yeast homolog of Ran-binding-protein-1 (RanBP1), a known
      coregulator of the Ran GTPase cycle. Both mutations result in single amino acid
      substitutions of evolutionarily conserved residues (A91D and R127K, respectively)
      in the Ran-binding domain of Yrb1. The altered proteins have reduced affinity for
      Ran (Gsp1) in vivo. After shift to restrictive temperature, both mutants display
      impaired nuclear protein import and one also reduces poly(A)+ RNA export,
      suggesting a primary defect in nucleocytoplasmic trafficking. Consistent with
      this conclusion, both yrb1ts mutations display deleterious genetic interactions
      with mutations in many other genes involved in nucleocytoplasmic transport,
      including SRP1 (alpha-importin) and several beta-importin family members. These
      yrb1ts alleles were isolated by their ability to suppress two different types of
      mating-defective mutants (respectively, fus1Delta and ste5ts), indicating that
      reduction in nucleocytoplasmic transport enhances mating proficiency. Indeed, in
      both yrb1ts mutants, Ste5 (scaffold protein for the pheromone response MAPK
      cascade) is mislocalized to the cytosol, even in the absence of pheromone. Also,
      both yrb1ts mutations suppress the mating defect of a null mutation in MSN5,
      which encodes the receptor for pheromone-stimulated nuclear export of Ste5. Our
      results suggest that reimport of Ste5 into the nucleus is important in
      downregulating mating response.

PMID- 11238398
TI  - Genes encoding ribosomal proteins Rps0A/B of Saccharomyces cerevisiae interact
      with TOM1 mutants defective in ribosome synthesis.
AB  - The Saccharomyces cerevisiae RPS0A/B genes encode proteins of the 40S ribosomal
      subunit that are required for the maturation of 18S rRNA. We show here that the
      RPS0 genes interact genetically with TOM1. TOM1 encodes a member of the hect
      domain-containing E3 ubiquitin-protein ligase family that is required for growth
      at elevated temperatures. Mutant alleles of the RPS0 and TOM1 genes have
      synergistic effects on cell growth at temperatures permissive for TOM1 mutants.
      Moreover, the growth arrest of TOM1 mutants at elevated temperatures is partially
      suppressed by overexpression of RPS0A/B. Strains with mutant alleles of TOM1 are
      defective in multiple steps in rRNA processing, and interactions between RPS0A/B
      and TOM1 stem, in part, from their roles in the maturation of ribosomal subunits.
      Ribosome synthesis is therefore included among the cellular processes governed by
      members of the hect-domain-containing E3 ubiquitin-protein ligase family.

PMID- 11238399
TI  - Overlapping functions of the yeast oxysterol-binding protein homologues.
AB  - The Saccharomyces cerevisiae genome encodes seven homologues of the mammalian
      oxysterol-binding protein (OSBP), a protein implicated in lipid trafficking and
      sterol homeostasis. To determine the functions of the yeast OSBP gene family
      (OSH1-OSH7), we used a combination of genetics, genomics, and sterol lipid
      analysis to characterize OSH deletion mutants. All 127 combinations and
      permutations of OSH deletion alleles were constructed. Individual OSH genes were
      not essential for yeast viability, but the elimination of the entire gene family
      was lethal. Thus, the family members shared an essential function. In addition,
      the in vivo depletion of all Osh proteins disrupted sterol homeostasis. Like
      mutants that affect ergosterol production, the viable combinations of OSH
      deletion alleles exhibited specific sterol-related defects. Although none of the
      single OSH deletion mutants was defective for growth, gene expression profiles
      revealed that each mutant had a characteristic molecular phenotype. Therefore,
      each gene performed distinct nonessential functions and contributed to a common
      essential function. Our findings indicated that OSH genes performed a multitude
      of nonessential roles defined by specific subsets of the genes and that most
      shared at least one essential role potentially linked to changes in sterol lipid
      levels.

PMID- 11238400
TI  - Yeast frameshift suppressor mutations in the genes coding for transcription
      factor Mbf1p and ribosomal protein S3: evidence for autoregulation of S3
      synthesis.
AB  - The SUF13 and SUF14 genes were identified among extragenic suppressors of +1
      frameshift mutations. SUF13 is synonymous with MBF1, a single-copy nonessential
      gene coding for a POLII transcription factor. The suf13-1 mutation is a two
      nucleotide deletion in the SUF13/MBF1 coding region. A suf13::TRP1 null mutant
      suppresses +1 frameshift mutations, indicating that suppression is caused by loss
      of SUF13 function. The suf13-1 suppressor alters sensitivity to aminoglycoside
      antibiotics and reduces the accumulation of his4-713 mRNA, suggesting that
      suppression is mediated at the translational level. The SUF14 gene is synonymous
      with RPS3, a single-copy essential gene that codes for the ribosomal protein S3.
      The suf14-1 mutation is a missense substitution in the coding region. Increased
      expression of S3 limits the accumulation of SUF14 mRNA, suggesting that
      expression is autoregulated. A frameshift mutation in SUF14 that prevents full
      length translation eliminated regulation, indicating that S3 is required for
      regulation. Using CUP1-SUF14 and SUF14-lacZ fusions, run-on transcription assays,
      and estimates of mRNA half-life, our results show that transcription plays a
      minor role if any in regulation and that the 5'-UTR is necessary but not
      sufficient for regulation. A change in mRNA decay rate may be the primary
      mechanism for regulation.

PMID- 11238401
TI  - The git5 Gbeta and git11 Ggamma form an atypical Gbetagamma dimer acting in the
      fission yeast glucose/cAMP pathway.
AB  - Fission yeast adenylate cyclase, like mammalian adenylate cyclases, is regulated
      by a heterotrimeric G protein. The gpa2 Galpha and git5 Gbeta are both required
      for glucose-triggered cAMP signaling. The git5 Gbeta is a unique member of the
      Gbeta family in that it lacks an amino-terminal coiled-coil domain shown to be
      essential for mammalian Gbeta folding and interaction with Ggamma subunits. Using
      a git5 bait in a two-hybrid screen, we identified the git11 Ggamma gene. Co
      immunoprecipitation studies confirm the composition of this Gbetagamma dimer.
      Cells deleted for git11 are defective in glucose repression of both fbp1
      transcription and sexual development, resembling cells lacking either the gpa2
      Galpha or the git5 Gbeta. Overexpression of the gpa2 Galpha partially suppresses
      loss of either the git5 Gbeta or the git11 Ggamma, while mutational activation of
      the Galpha fully suppresses loss of either Gbeta or Ggamma. Deletion of gpa2
      (Galpha), git5 (Gbeta), or git11 (Ggamma) confer quantitatively distinct effects
      on fbp1 repression, indicating that the gpa2 Galpha subunit remains partially
      active in the absence of the Gbetagamma dimer and that the git5 Gbeta subunit
      remains partially active in the absence of the git11 Ggamma subunit. The addition
      of the CAAX box from the git11 Ggamma to the carboxy-terminus of the git5 Gbeta
      partially suppresses the loss of the Ggamma. Thus the Ggamma in this system is
      presumably required for localization of the Gbetagamma dimer but not for folding
      of the Gbeta subunit. In mammalian cells, the essential roles of the Gbeta amino
      terminal coiled-coil domains and Ggamma partners in Gbeta folding may therefore
      reflect a mechanism used by cells that express multiple forms of both Gbeta and
      Ggamma subunits to regulate the composition and activity of its G proteins.

PMID- 11238402
TI  - Regulatory mechanisms controlling expression of the DAN/TIR mannoprotein genes
      during anaerobic remodeling of the cell wall in Saccharomyces cerevisiae.
AB  - The DAN/TIR genes of Saccharomyces cerevisiae encode homologous mannoproteins,
      some of which are essential for anaerobic growth. Expression of these genes is
      induced during anaerobiosis and in some cases during cold shock. We show that
      several heme-responsive mechanisms combine to regulate DAN/TIR gene expression.
      The first mechanism employs two repression factors, Mox1 and Mox2, and an
      activation factor, Mox4 (for mannoprotein regulation by oxygen). The genes
      encoding these proteins were identified by selecting for recessive mutants with
      altered regulation of a dan1::ura3 fusion. MOX4 is identical to UPC2, encoding a
      binucleate zinc cluster protein controlling expression of an anaerobic sterol
      transport system. Mox4/Upc2 is required for expression of all the DAN/TIR genes.
      It appears to act through a consensus sequence termed the AR1 site, as does Mox2.
      The noninducible mox4Delta allele was epistatic to the constitutive mox1 and mox2
      mutations, suggesting that Mox1 and Mox2 modulate activation by Mox4 in a heme
      dependent fashion. Mutations in a putative repression domain in Mox4 caused
      constitutive expression of the DAN/TIR genes, indicating a role for this domain
      in heme repression. MOX4 expression is induced both in anaerobic and cold-shocked
      cells, so heme may also regulate DAN/TIR expression through inhibition of
      expression of MOX4. Indeed, ectopic expression of MOX4 in aerobic cells resulted
      in partially constitutive expression of DAN1. Heme also regulates expression of
      some of the DAN/TIR genes through the Rox7 repressor, which also controls
      expression of the hypoxic gene ANB1. In addition Rox1, another heme-responsive
      repressor, and the global repressors Tup1 and Ssn6 are also required for full
      aerobic repression of these genes.

PMID- 11238403
TI  - The Saccharomyces cerevisiae MUM2 gene interacts with the DNA replication
      machinery and is required for meiotic levels of double strand breaks.
AB  - The Saccharomyces cerevisiae MUM2 gene is essential for meiotic, but not mitotic,
      DNA replication and thus sporulation. Genetic interactions between MUM2 and a
      component of the origin recognition complex and polymerase alpha-primase suggest
      that MUM2 influences the function of the DNA replication machinery. Early meiotic
      gene expression is induced to a much greater extent in mum2 cells than in meiotic
      cells treated with the DNA synthesis inhibitor hydroxyurea. This result indicates
      that the mum2 meiotic arrest is downstream of the arrest induced by hydroxyurea
      and suggests that DNA synthesis is initiated in the mutant. Genetic analyses
      indicate that the recombination that occurs in mum2 mutants is dependent on the
      normal recombination machinery and on synaptonemal complex components and
      therefore is not a consequence of lesions created by incompletely replicated DNA.
      Both meiotic ectopic and allelic recombination are similarly reduced in the mum2
      mutant, and the levels are consistent with the levels of meiosis-specific DSBs
      that are generated. Cytological analyses of mum2 mutants show that chromosome
      pairing and synapsis occur, although at reduced levels compared to wild type.
      Given the near-wild-type levels of meiotic gene expression, pairing, and
      synapsis, we suggest that the reduction in DNA replication is directly
      responsible for the reduced level of DSBs and meiotic recombination.

PMID- 11238404
TI  - Functional redundancies, distinct localizations and interactions among three
      fission yeast homologs of centromere protein-B.
AB  - Several members of protein families that are conserved in higher eukaryotes are
      known to play a role in centromere function in the fission yeast
      Schizosaccharomyces pombe, including two homologs of the mammalian centromere
      protein CENP-B, Abp1p and Cbh1p. Here we characterize a third S. pombe CENP-B
      homolog, Cbh2p (CENP-B homolog 2). cbh2Delta strains exhibited a modest elevation
      in minichromosome loss, similar to cbh1Delta or abp1Delta strains. cbh2Delta
      cbh1Delta strains showed little difference in growth or minichromosome loss rate
      when compared to single deletion strains. In contrast, cbh2Delta abp1Delta
      strains displayed dramatic morphological and chromosome segregation defects, as
      well as enhancement of the slow-growth phenotype of abp1Delta strains, indicating
      partial functional redundancy between these proteins. Both cbh2Delta abp1Delta
      and cbh1Delta abp1Delta strains also showed strongly enhanced sensitivity to a
      microtubule-destabilizing drug, consistent with a mitotic function for these
      proteins. Cbh2p was localized to the central core and core-associated repeat
      regions of centromeric heterochromatin, but not at several other centromeric and
      arm locations tested. Thus, like its mammalian counterpart, Cbh2p appeared to be
      localized exclusively to a portion of centromeric heterochromatin. In contrast,
      Abp1p was detected in both centromeric heterochromatin and in chromatin at two of
      three replication origins tested. Cbh2p and Abp1p homodimerized in the budding
      yeast two-hybrid assay, but did not interact with each other. These results
      suggest that indirect cooperation between different CENP-B-like DNA binding
      proteins with partially overlapping chromatin distributions helps to establish a
      functional centromere.

PMID- 11238406
TI  - Creation of low-copy integrated transgenic lines in Caenorhabditis elegans.
AB  - In Caenorhabditis elegans, transgenic lines are typically created by injecting
      DNA into the hermaphrodite germline to form multicopy extrachromosomal DNA
      arrays. This technique is a reliable means of expressing transgenes in C.
      elegans, but its use has limitations. Because extrachromosomal arrays are
      semistable, only a fraction of the animals in a transgenic extrachromosomal array
      line are transformed. In addition, because extrachromosomal arrays can contain
      hundreds of copies of the transforming DNA, transgenes may be overexpressed,
      misexpressed, or silenced. We have developed an alternative method for C. elegans
      transformation, using microparticle bombardment, that produces single- and low
      copy chromosomal insertions. Using this method, we find that it is possible to
      create integrated transgenic lines that reproducibly express GFP reporter
      constructs without the variations in expression level and pattern frequently
      exhibited by extrachromosomal array lines. In addition, we find that low-copy
      integrated lines can also be used to express transgenes in the C. elegans
      germline, where conventional extrachromosomal arrays typically fail to express
      due to germline silencing.

PMID- 11238405
TI  - Transcriptional regulators of the Schizosaccharomyces pombe fbp1 gene include two
      redundant Tup1p-like corepressors and the CCAAT binding factor activation
      complex.
AB  - The Schizosaccharomyces pombe fbp1 gene, which encodes fructose-1,6-bis
      phosphatase, is transcriptionally repressed by glucose through the activation of
      the cAMP-dependent protein kinase A (PKA) and transcriptionally activated by
      glucose starvation through the activation of a mitogen-activated protein kinase
      (MAPK). To identify transcriptional regulators acting downstream from or in
      parallel to PKA, we screened an adh-driven cDNA plasmid library for genes that
      increase fbp1 transcription in a strain with elevated PKA activity. Two such
      clones express amino-terminally truncated forms of the S. pombe tup12 protein
      that resembles the Saccharomyces cerevisiae Tup1p global corepressor. These
      clones appear to act as dominant negative alleles. Deletion of both tup12 and the
      closely related tup11 gene causes a 100-fold increase in fbp1-lacZ expression,
      indicating that tup11 and tup12 are redundant negative regulators of fbp1
      transcription. In strains lacking tup11 and tup12, the atf1-pcr1 transcriptional
      activator continues to play a central role in fbp1-lacZ expression; however, spc1
      MAPK phosphorylation of atf1 is no longer essential for its activation. We
      discuss possible models for the role of tup11- and tup12-mediated repression with
      respect to signaling from the MAPK and PKA pathways. A third clone identified in
      our screen expresses the php5 protein subunit of the CCAAT-binding factor (CBF).
      Deletion of php5 reduces fbp1 expression under both repressed and derepressed
      conditions. The CBF appears to act in parallel to atf1-pcr1, although it is
      unclear whether or not CBF activity is regulated by PKA.

PMID- 11238407
TI  - pitkin(D), a novel gain-of-function enhancer of position-effect variegation,
      affects chromatin regulation during oogenesis and early embryogenesis in
      Drosophila.
AB  - The vast majority of the >100 modifier genes of position-effect variegation (PEV)
      in Drosophila have been identified genetically as haplo-insufficient loci. Here,
      we describe pitkin(Dominant) (ptn(D)), a gain-of-function enhancer mutation of
      PEV. Its exceptionally strong enhancer effect is evident as elevated spreading of
      heterochromatin-induced gene silencing along euchromatic regions in variegating
      rearrangements. The ptn(D) mutation causes ectopic binding of the SU(VAR)3-9
      heterochromatin protein at many euchromatic sites and, unlike other modifiers of
      PEV, it also affects stable position effects. Specifically, it induces silencing
      of white+ transgenes inserted at a wide variety of euchromatic sites. ptn(D) is
      associated with dominant female sterility. +/+ embryos produced by ptn(D)/+
      females mated with wild-type males die at the end of embryogenesis, whereas the
      ptn(D)/+ sibling embryos arrest development at cleavage cycle 1-3, due to a
      combined effect of maternally provided mutant product and an early zygotic lethal
      effect of ptn(D). This is the earliest zygotic effect of a mutation so far
      reported in Drosophila. Germ-line mosaics show that ptn+ function is required for
      normal development in the female germ line. These results, together with effects
      on PEV and white+ transgenes, are consistent with the hypothesis that the ptn
      gene plays an important role in chromatin regulation during development of the
      female germ line and in early embryogenesis.

PMID- 11238408
TI  - Genomic organization and characterization of the white locus of the Mediterranean
      fruitfly, Ceratitis capitata.
AB  - An approximately 14-kb region of genomic DNA encoding the wild-type white eye
      (w+) color gene from the medfly, Ceratitis capitata has been cloned and
      characterized at the molecular level. Comparison of the intron-exon organization
      of this locus among several dipteran insects reveals distinct organizational
      patterns that are consistent with the phylogenetic relationships of these flies
      and the dendrogram of the predicted primary amino acid sequence of the white
      loci. An examination of w+ expression during medfly development has been carried
      out, displaying overall similarity to corresponding studies for white gene
      homologues in Drosophila melanogaster and other insects. Interestingly, we have
      detected two phenotypically neutral allelic forms of the locus that have arisen
      as the result of an apparently novel insertion or deletion event located in the
      large first intron of the medfly white locus. Cloning and sequencing of two
      mutant white alleles, w1 and w2, from the we,wp and M245 strains, respectively,
      indicate that the mutant conditions in these strains are the result of
      independent events--a frameshift mutation in exon 6 for w1 and a deletion
      including a large part of exon 2 in the case of w2.

PMID- 11238409
TI  - Whole-genome effects of ethyl methanesulfonate-induced mutation on nine
      quantitative traits in outbred Drosophila melanogaster.
AB  - We induced mutations in Drosophila melanogaster males by treating them with 21.2
      mm ethyl methanesulfonate (EMS). Nine quantitative traits (developmental time,
      viability, fecundity, longevity, metabolic rate, motility, body weight, and
      abdominal and sternopleural bristle numbers) were measured in outbred
      heterozygous F3 (viability) or F2 (all other traits) offspring from the treated
      males. The mean values of the first four traits, which are all directly related
      to the life history, were substantially affected by EMS mutagenesis: the
      developmental time increased while viability, fecundity, and longevity declined.
      In contrast, the mean values of the other five traits were not significantly
      affected. Rates of recessive X-linked lethals and of recessive mutations at
      several loci affecting eye color imply that our EMS treatment was equivalent to
      approximately 100 generations of spontaneous mutation. If so, our data imply that
      one generation of spontaneous mutation increases the developmental time by 0.09%
      at 20 degrees and by 0.04% at 25 degrees, and reduces viability under harsh
      conditions, fecundity, and longevity by 1.35, 0.21, and 0.08%, respectively.
      Comparison of flies with none, one, and two grandfathers (or greatgrandfathers,
      in the case of viability) treated with EMS did not reveal any significant
      epistasis among the induced mutations.

PMID- 11238410
TI  - fumble encodes a pantothenate kinase homolog required for proper mitosis and
      meiosis in Drosophila melanogaster.
AB  - A number of fundamental processes comprise the cell division cycle, including
      spindle formation, chromosome segregation, and cytokinesis. Our current
      understanding of these processes has benefited from the isolation and analysis of
      mutants, with the meiotic divisions in the male germline of Drosophila being
      particularly well suited to the identification of the required genes. We show
      here that the fumble (fbl) gene is required for cell division in Drosophila. We
      find that dividing cells in fbl-deficient testes exhibit abnormalities in bipolar
      spindle organization, chromosome segregation, and contractile ring formation.
      Cytological analysis of larval neuroblasts from null mutants reveals a reduced
      mitotic index and the presence of polyploid cells. Molecular analysis
      demonstrates that fbl encodes three protein isoforms, all of which contain a
      domain with high similarity to the pantothenate kinases of A. nidulans and mouse.
      The largest Fumble isoform is dispersed in the cytoplasm during interphase,
      concentrates around the spindle at metaphase, and localizes to the spindle
      midbody at telophase. During early embryonic development, the protein localizes
      to areas of membrane deposition and/or rearrangement, such as the metaphase and
      cellularization furrows. Given the role of pantothenate kinase in production of
      Coenzyme A and in phospholipid biosynthesis, this pattern of localization is
      suggestive of a role for fbl in membrane synthesis. We propose that abnormalities
      in synthesis and redistribution of membranous structures during the cell division
      cycle underlie the cell division defects in fbl mutant cells.

PMID- 11238411
TI  - An amplified fragment length polymorphism map of the silkworm.
AB  - The silkworm (Bombyx mori L.) is a lepidopteran insect with a long history of
      significant agricultural value. We have constructed the first amplified fragment
      length polymorphism (AFLP) genetic linkage map of the silkworm B. mori at a LOD
      score of 2.5. The mapping AFLP markers were genotyped in 47 progeny from a
      backcross population of the cross no. 782 x od100. A total of 1248 (60.7%)
      polymorphic AFLP markers were detected with 35 PstI/TaqI primer combinations.
      Each of the primer combinations generated an average of 35.7 polymorphic AFLP
      markers. A total of 545 (44%) polymorphic markers are consistent with the
      expected segregation ratio of 1:1 at the significance level of P = 0.05. Of the
      545 polymorphic markers, 356 were assigned to 30 linkage groups. The number of
      markers on linkage groups ranged from 4 to 36. There were 21 major linkage groups
      with 7-36 markers and 9 relatively small linkage groups with 4-6 markers. The 30
      linkage groups varied in length from 37.4 to 691.0 cM. The total length of this
      AFLP linkage map was 6512 cM. Genetic distances between two neighboring markers
      on the same linkage group ranged from 0.2 to 47 cM with an average of 18.2 cM.
      The sex-linked gene od was located between the markers P1T3B40 and P3T3B27 at the
      end of group 3, indicating that AFLP linkage group 3 was the Z (sex) chromosome.
      This work provides an essential basic map for constructing a denser linkage map
      and for mapping genes underlying agronomically important traits in the silkworm
      B. mori L.

PMID- 11238412
TI  - Molecular nature of 11 spontaneous de novo mutations in Drosophila melanogaster.
AB  - To investigate the molecular nature and rate of spontaneous mutation in
      Drosophila melanogaster, we screened 887,000 individuals for de novo recessive
      loss-of-function mutations at eight loci that affect eye color. In total, 28
      mutants were found in 16 independent events (13 singletons and three clusters).
      The molecular nature of the 13 events was analyzed. Coding exons of the locus
      were affected by insertions or deletions >100 nucleotides long (6 events), short
      frameshift insertions or deletions (4 events), and replacement nucleotide
      substitutions (1 event). In the case of 2 mutant alleles, coding regions were not
      affected. Because approximately 70% of spontaneous de novo loss-of-function
      mutations in Homo sapiens are due to nucleotide substitutions within coding
      regions, insertions and deletions appear to play a much larger role in
      spontaneous mutation in D. melanogaster than in H. sapiens. If so, the per
      nucleotide mutation rate in D. melanogaster may be lower than in H. sapiens, even
      if their per locus mutation rates are similar.

PMID- 11238413
TI  - Adaptive evolution of Cid, a centromere-specific histone in Drosophila.
AB  - Centromeric DNA is generally composed of large blocks of tandem satellite repeats
      that change rapidly due to loss of old arrays and expansion of new repeat
      classes. This extreme heterogeneity of centromeric DNA is difficult to reconcile
      with the conservation of the eukaryotic chromosome segregation machinery. Histone
      H3-like proteins, including Cid in Drosophila melanogaster, are a unique
      chromatin component of centromeres. In comparisons between closely related
      species of Drosophila, we find an excess of replacement changes that have been
      fixed since the separation of D. melanogaster and D. simulans, suggesting
      adaptive evolution. The last adaptive changes appear to have occurred recently,
      as evident from a reduction in polymorphism in the melanogaster lineage. Adaptive
      evolution has occurred both in the long N-terminal tail as well as in the histone
      fold of Cid. In the histone fold, the replacement changes have occurred in the
      region proposed to mediate binding to DNA. We propose that this rapid evolution
      of Cid is driven by a response to the changing satellite repeats at centromeres.
      Thus, centromeric H3-like proteins may act as adaptors between evolutionarily
      labile centromeric DNA and the conserved kinetochore machinery.

PMID- 11238414
TI  - Integration of the Aedes aegypti mosquito genetic linkage and physical maps.
AB  - Two approaches were used to correlate the Aedes aegypti genetic linkage map to
      the physical map. STS markers were developed for previously mapped RFLP-based
      genetic markers so that large genomic clones from cosmid libraries could be found
      and placed to the metaphase chromosome physical maps using standard FISH methods.
      Eight cosmids were identified that contained eight RFLP marker sequences, and
      these cosmids were located on the metaphase chromosomes. Twenty-one cDNAs were
      mapped directly to metaphase chromosomes using a FISH amplification procedure.
      The chromosome numbering schemes of the genetic linkage and physical maps
      corresponded directly and the orientations of the genetic linkage maps for
      chromosomes 2 and 3 were inverted relative to the physical maps. While the
      chromosome 2 linkage map represented essentially 100% of chromosome 2,
      approximately 65% of the chromosome 1 linkage map mapped to only 36% of the short
      p-arm and 83% of the chromosome 3 physical map contained the complete genetic
      linkage map. Since the genetic linkage map is a RFLP cDNA-based map, these data
      also provide a minimal estimate for the size of the euchromatic regions. The
      implications of these findings on positional cloning in A. aegypti are discussed.

PMID- 11238415
TI  - A targeted gene knockout in Drosophila.
AB  - We previously described a method for targeted homologous recombination at the
      yellow gene of Drosophila melanogaster. Because only a single gene was targeted,
      further work was required to show whether the method could be extended to become
      generally useful for gene modification in Drosophila. We have now used this
      method to produce a knockout of the autosomal pugilist gene by homologous
      recombination between the endogenous locus and a 2.5-kb DNA fragment. This was
      accomplished solely by tracking the altered genetic linkage of an arbitrary
      marker gene as the targeting DNA moved from chromosome X or 2 to chromosome 3.
      The results indicate that this method of homologous recombination is likely to be
      generally useful for Drosophila gene targeting.

PMID- 11238416
TI  - Ethylnitrosourea-induced mutation in mice leads to the expression of a novel
      protein in the eye and to dominant cataracts.
AB  - A novel ENU-induced mutation in the mouse leading to a nuclear and zonular
      opacity of the eye lens (Aey1) was mapped to chromosome 1 between the markers
      D1Mit303 and D1Mit332. On the basis of the chromosomal position, the gamma
      crystallin encoding gene cluster (Cryg) and the betaA2-crystallin encoding gene
      Cryba2 were tested as candidate genes. An A --> T mutation destroys the start
      codon of the Cryge gene in the mutants; this mutation was confirmed by the
      absence of a restriction site for NcoI in the corresponding genomic fragment of
      homozygous mutants. The next in-frame start codon is 129 bp downstream; this
      predicted truncated gammaE-crystallin consists of 131 amino acids, resulting in a
      molecular mass of 14 kD. However, another open reading frame was observed just 19
      bp downstream of the regular Cryge start codon, resulting in a protein of 119
      amino acids and a calculated molecular weight of 13 kD. Western blot analysis
      using polyclonal antibodies against gamma-crystallins or the novel Aey1-specific
      protein demonstrated the specific expression of the Aey1 protein in the
      cataractous lenses only; the truncated form of the gammaE-crystallin could not be
      detected. Therefore, it is concluded that the novel protein destroys the
      sensitive cellular structure of the eye lens.

PMID- 11238417
TI  - Arabidopsis and Brassica comparative genomics: sequence, structure and gene
      content in the ABI-Rps2-Ck1 chromosomal segment and related regions.
AB  - The region corresponding to the ABI1-Rps2-Ck1 segment on chromosome 4 of
      Arabidopsis thaliana was sequenced in Brassica oleracea. Similar to A. thaliana,
      the B. oleracea homolog BoRps2 is present in single copy. The B. oleracea
      orthologous segment was located on chromosome 4 and can be distinguished by the
      presence of an N-myristoyl transferase coding gene (N-myr) between the Rps2 and
      Ck1 (BoCk1a) genes. The N-myr homologs in Arabidopsis are on chromosomes 2 and 5.
      Additional homologs for Ck1 are located on these two chromosomes. A second Ck1
      homolog found on B. oleracea (BoCk1b) chromosome 7 served to define another
      orthologous segment located in Arabidopsis chromosome 1. The two segments
      displayed identical gene content and order in both species, namely BoCK1b, a gene
      encoding a hypothetical protein (BohypothA) and transcription factor eiF4A. High
      levels of sequence identity were observed for the coding sequences of all genes
      examined. Although in general larger spacers were found in Brassica than in A.
      thaliana, this was not always the case. Promoters were poorly conserved, except
      for several sequence stretches of a few nucleotides. Comparative sequencing
      revealed microsyntenic changes resulting from chromosomal structural
      rearrangements, which are often undetectable by genetic mapping.

PMID- 11238418
TI  - Network analysis provides insights into evolution of 5S rDNA arrays in Triticum
      and Aegilops.
AB  - We have used network analysis to study gene sequences of the Triticum and
      Aegilops 5S rDNA arrays, as well as the spacers of the 5S-DNA-A1 and 5S-DNA-2
      loci. Network analysis describes relationships between 5S rDNA sequences in a
      more realistic fashion than conventional tree building because it makes fewer
      assumptions about the direction of evolution, the extent of sexual isolation, and
      the pattern of ancestry and descent. The networks show that the 5S rDNA sequences
      of Triticum and Aegilops species are related in a reticulate manner around
      principal nodal sequences. The spacer networks have multiple principal nodes of
      considerable antiquity but the gene network has just one principal node,
      corresponding to the correct gene sequence. The networks enable orthologous
      groups of spacer sequences to be identified. When orthologs are compared it is
      seen that the patterns of intra- and interspecific diversity are similar for both
      genes and spacers. We propose that 5S rDNA arrays combine sequence conservation
      with a large store of mutant variations, the number of correct gene copies within
      an array being the result of neutral processes that act on gene and spacer
      regions together.

PMID- 11238419
TI  - The length of the intact donor chromosome segment around a target gene in marker
      assisted backcrossing.
AB  - Recurrent backcrossing is an established procedure to transfer target genes from
      a donor into the genetic background of a recipient genotype. By assessing the
      parental origin of alleles at markers flanking the target locus one can select
      individuals with a short intact donor chromosome segment around the target gene
      and thus reduce the linkage drag. We investigated the probability distribution of
      the length of the intact donor chromosome segment around the target gene in
      recurrent backcrossing with selection for heterozygosity at the target locus and
      homozygosity for the recurrent parent allele at flanking markers for a diploid
      species. Assuming no interference in crossover formation, we derived the
      cumulative density function, probability density function, expected value, and
      variance of the length of the intact chromosome segment for the following cases:
      (1) backcross generations prior to detection of a recombinant individual between
      the target gene and the flanking marker; (2) the backcross generation in which
      for the first time a recombinant individual is detected, which is selected for
      further backcrossing; and (3) subsequent backcross generations after selection of
      a recombinant. Examples are given of how these results can be applied to
      investigate the efficiency of marker-assisted backcrossing for reducing the
      length of the intact donor chromosome segment around the target gene under
      various situations relevant in breeding and genetic research.

PMID- 11238420
TI  - Biased estimation of the recombination fraction using half-sib families and
      informative offspring.
AB  - A maximum-likelihood method to estimate the recombination fraction and its
      sampling variance using informative and noninformative half-sib offspring is
      derived. Estimates of the recombination fraction are biased up to 20 cM when
      noninformative offspring are discarded. In certain scenarios, the sampling
      variance can be increased or reduced up to fivefold due to the bias in estimating
      the recombination fraction and the LOD score can be reduced up to 5 units when
      discarding noninformative offspring. Comparison of the estimates of recombination
      fraction, map distance, and LOD score when constructing a genetic map with 251
      two-point linkage analyses and six families of Norwegian cattle was carried out
      to evaluate the implications of discarding noninformative offspring in practical
      situations. The average discrepancies in absolute value (average difference when
      using and neglecting noninformative offspring) were 0.0146, 1.64 cM, and 2.61 for
      the recombination fraction, map distance, and the LOD score, respectively. A
      method for simultaneous estimation of allele frequencies in the dam population
      and a transmission disequilibrium parameter is proposed. This method might
      account for the bias in estimating allele frequencies in the dam population when
      the half-sib offspring is selected for production traits.

PMID- 11238421
TI  - Construction of a genetic linkage map in tetraploid species using molecular
      markers.
AB  - This article presents methodology for the construction of a linkage map in an
      autotetraploid species, using either codominant or dominant molecular markers
      scored on two parents and their full-sib progeny. The steps of the analysis are
      as follows: identification of parental genotypes from the parental and offspring
      phenotypes; testing for independent segregation of markers; partition of markers
      into linkage groups using cluster analysis; maximum-likelihood estimation of the
      phase, recombination frequency, and LOD score for all pairs of markers in the
      same linkage group using the EM algorithm; ordering the markers and estimating
      distances between them; and reconstructing their linkage phases. The information
      from different marker configurations about the recombination frequency is
      examined and found to vary considerably, depending on the number of different
      alleles, the number of alleles shared by the parents, and the phase of the
      markers. The methods are applied to a simulated data set and to a small set of
      SSR and AFLP markers scored in a full-sib population of tetraploid potato.

PMID- 11238422
TI  - Determination of the number of conserved chromosomal segments between species.
AB  - Genomic divergence between species can be quantified in terms of the number of
      chromosomal rearrangements that have occurred in the respective genomes following
      their divergence from a common ancestor. These rearrangements disrupt the
      structural similarity between genomes, with each rearrangement producing
      additional, albeit shorter, conserved segments. Here we propose a simple
      statistical approach on the basis of the distribution of the number of markers in
      contiguous sets of autosomal markers (CSAMs) to estimate the number of conserved
      segments. CSAM identification requires information on the relative locations of
      orthologous markers in one genome and only the chromosome number on which each
      marker resides in the other genome. We propose a simple mathematical model that
      can account for the effect of the nonuniformity of the breakpoints and markers on
      the observed distribution of the number of markers in different conserved
      segments. Computer simulations show that the number of CSAMs increases linearly
      with the number of chromosomal rearrangements under a variety of conditions.
      Using the CSAM approach, the estimate of the number of conserved segments between
      human and mouse genomes is 529 +/- 84, with a mean conserved segment length of
      2.8 cM. This length is <40% of that currently accepted for human and mouse
      genomes. This means that the mouse and human genomes have diverged at a rate of
      approximately 1.15 rearrangements per million years. By contrast, mouse and rat
      are diverging at a rate of only approximately 0.74 rearrangements per million
      years.

PMID- 11238424
TI  - The challenge of chloroquine-resistant malaria in sub-Saharan Africa.
AB  - For the last decade chloroquine-resistant Plasmodium falciparum (CRPF) has spread
      explosively in sub-Saharan Africa. In some areas of the continent, CRPF is so
      intense that chloroquine can hardly be said to have any efficacy. There is
      emerging evidence that CRPF is linked with increased incidence of mortality,
      severe disease and emergence of epidemics. Whereas the normal response to this
      trend of events would be replacing chloroquine with another effective drug, such
      a decision is hampered by the limited number of antimalarials currently
      available. There is a fear that changing too early would lead to depletion of
      available drugs. Yet a delay may be costly and catastrophic. Since the
      development of new antimalarials is deemed commercially unviable by high-income
      countries, there is need for a pan-African project aimed at the development of
      new antimalarials. Such a project could be jointly funded from African
      governments and the donor community under the coordination of either the World
      Health Organization or the Organization of African Unity. To delay the emergence
      and spread of resistance by P. falciparum to new and old drugs, there is need
      for: improving rational drugs use; limiting mass use of drugs as in
      chemoprophylaxis and in medicated salt; and increasing the use of impregnated bed
      nets.

PMID- 11238425
TI  - Ten recommendations to improve use of medicines in developing countries.
AB  - Inappropriate prescribing reduces the quality of medical care and leads to a
      waste of resources. To address these problems, a variety of educational and
      administrative approaches to improve prescribing have been tried. This article
      reviews the experiences of the last decade in order to identify which
      interventions have proven effective in developing countries, and suggests a range
      of policy options for health planners and managers. Considering the magnitude of
      resources that are wasted on inappropriately used drugs, many promising
      interventions are relatively inexpensive. Simple methods are available to monitor
      drug use in a standardized way and to identify inefficiencies. Intervention
      approaches that have proved effective in some settings are: standard treatment
      guidelines; essential drugs lists; pharmacy and therapeutics committees; problem
      based basic professional training; and targeted in-service training of health
      workers. Some other interventions, such as training of drug sellers, education
      based on group processes and public education, need further testing, but should
      be supported. Several simplistic approaches have proven ineffective, such as
      disseminating prescribing information or clinical guidelines in written form
      only. Two issues that will require a long-term strategic approach are improving
      prescribing in the private sector and monitoring the impacts of health sector
      reform. Sufficient evidence is now available to persuade policy-makers that it is
      possible to promote rational drug use. If such effective strategies are followed,
      the quality of health care can be improved and drug expenditures reduced.

PMID- 11238426
TI  - Early entrance to the job market and its effect on adult health: evidence from
      Brazil.
AB  - OBJECTIVE: To determine the effect of employment in childhood on self-reported
      health in adulthood. METHOD: A cross-sectional household survey, with households
      selected through two-stage sampling, in urban and rural areas in the northeast
      and southeast of Brazil. A total of 4940 individuals, aged between 18 and 65
      years, were included. The main outcome measure was self-reported health. RESULTS:
      There has been a marked reduction in the proportion of people starting work
      during childhood although, even in the youngest age group, nearly 20% of males
      began work when under 10. Early entrance into the labour market is strongly
      associated with low levels of both education and income, with income
      differentials remaining at later ages. Age starting work is also linked to
      current household income, with approximately 35% of those starting work when 15
      or over currently in the top quartile of household income, compared with 12% of
      those starting work when under 10. Males, those living in rural areas, and non
      whites are most likely to start work early. In univariate analyses, the younger a
      person started working, the greater the probability of reporting less than good
      health status as an adult. This persists through all ages, although the
      difference attenuates with increasing age. In multivariate analyses, adjustment
      for education or household income substantially reduces the effect but fails to
      eliminate it in several age bands up to the age of 48, indicating that age
      starting work has an independent effect on self-reported health in adulthood.
      CONCLUSIONS: The debate about the appropriate policy response to child labour is
      complex, requiring a balance between protecting the health of the child and
      safeguarding the income of the family. These findings indicate the need for more
      research on the long-term sequelae of beginning work at an early age.

PMID- 11238427
TI  - Antenatal syphilis in sub-Saharan Africa: missed opportunities for mortality
      reduction.
AB  - PURPOSE: Between 4-15% of pregnant women are believed to be infected with
      syphilis in sub-Saharan Africa. Active infection with syphilis in pregnant women
      results in foetal or infant death or disability for 50-80% of affected
      pregnancies, and is a major cause of adult morbidity as well. Antenatal syphilis
      screening is cheap and effective; however, it is often poorly implemented in
      countries with high syphilis risk. This study sought to estimate the missed
      opportunities for antenatal syphilis screening in sub-Saharan Africa. METHODS:
      Survey data were collected from 22 ministries of health in sub-Saharan Africa,
      complemented by data from published sources and key informants. Informants
      described their country's policies and experience with antenatal syphilis
      screening and estimated their national syphilis screening rates. FINDINGS:
      Seventy-three percent of women are reported by WHO to receive antenatal care in
      the study countries. Of women in antenatal care, 38% were estimated by survey
      respondents to be screened for syphilis. Costs and the organization of services
      were the principal reported obstacles to screening. With syphilis seroprevalence
      estimated at 8.3%, approximately 1 640 000 pregnant women with syphilis are
      undetected annually, including 1 030 000 women who attend antenatal care.
      DISCUSSION: Syphilis testing and treatment is a cost-effective intervention that
      deserves much greater attention, particularly in sub-Saharan Africa and other
      countries where syphilis infection is high.

PMID- 11238428
TI  - The quality of care by private practitioners for sexually transmitted diseases in
      Uganda.
AB  - One of the limited number of strategies available to reduce the spread of human
      immunodeficiency virus (HIV) infections in sub-Saharan Africa is the effective
      treatment of other, curable, sexually transmitted diseases (STDs). At present, a
      large proportion of people with STDs either treat themselves at home or seek
      treatment from private sector practitioners (PSPs) rather than use publicly
      funded services. A randomized controlled trial of the efficacy of a behavioural
      intervention with or without improved STD services is being carried out in
      Masaka, a rural area of south-western Uganda. The trial involves three groups,
      each covering six parishes. People living in one group of parishes receive
      information, education and communication activities (IEC) to increase public
      awareness regarding STDs and HIV/AIDS. The second group receives the same IEC
      interventions with improved treatment of STDs by both public and private service
      providers. The third group receives community development activities unrelated to
      HIV. In order to improve our understanding of how the quality of care provided by
      PSPs might be ameliorated, we interviewed 36 PSPs in the trial area, and made an
      assessment of the care they were providing. We also carried out six focus group
      discussions with patients to obtain their opinions on private services. PSPs in
      the intervention arm of the trial, who had attended meetings dealing with the
      syndromic management of STDs, referred to syndromes 82% of the time compared with
      12% in the control arms, a mean difference of 70% (p < 0.001); stocked locally
      appropriate antibiotics 76% of the time compared with 52%, a mean difference of
      24% (p < 0.001); and are more likely to prescribe appropriate drugs 82% of the
      time compared with 27%, a mean difference of 55% (p < 0.001). This small study
      suggests that PSPs can help improve the management of STDs.

PMID- 11238429
TI  - Prevalence of HIV infection among former commercial plasma donors in rural
      eastern China.
AB  - BACKGROUND: Sporadic reports of HIV-1 infection among commercial plasma donors in
      China between 1994 and 1995. OBJECTIVES: (1) To determine the prevalence of HIV
      infection among repeat plasma donors; (2) to identify factors associated with HIV
      infection; and (3) to describe characteristics associated with secondary
      transmission. METHODS: Plasma/blood donors who had a history of donating
      plasma/blood before March 1, 1995, their spouses, and their children under 5
      years were recruited for a cross-sectional study. A questionnaire and an HIV test
      were collected anonymously. Information collected included demographic
      characteristics, sexual behaviour, recreational drug use and history of medical
      care and blood/plasma donation. HIV antibody was identified by the Hema-Strip
      rapid test and confirmed by Western blot. The prevalence of HIV infection was
      calculated and risk factors associated with infection determined by univariate
      analyses followed by multivariate modelling. RESULTS: A total of 1517 individuals
      were interviewed and tested, of whom 1043 adults admitted to donating plasma. The
      prevalence of HIV infection among plasma donors was 12.5% and among their non
      donor spouses was 2.1%. Prevalence was inversely related to educational level and
      was higher in married participants, but was not associated with medical care,
      drug abuse or multiple sexual partners. A higher frequency of plasma donation was
      directly associated with a higher risk of HIV infection. Multivariate analyses
      demonstrated that being HIV-positive was associated with being 30 to 49 years old
      [odds ratio (OR) = 1.9], donating both plasma and blood (OR = 2.5), and the
      frequency of plasma donation (OR = 14 for >10 donations per month). CONCLUSION:
      The study demonstrated that the prevalence of HIV infection in the commercial
      plasma donor population was alarmingly high. Many married individuals and those
      getting married in the future will transmit the virus to their spouses and future
      children. Plasma donors need to be alerted to the risk of being infected with HIV
      and of transmitting HIV to their families and others. Other countries can benefit
      from the experience of China in reducing the risk of HIV transmission from plasma
      donating.

PMID- 11238430
TI  - Utilization of private and public health-care providers for tuberculosis symptoms
      in Ho Chi Minh City, Vietnam.
AB  - In Vietnam, as in many other countries, tuberculosis (TB) control has long been
      organized exclusively within the public health-care system. However, recently the
      private health-care sector has become more important and private health-care
      providers currently have a role in TB care delivery in Vietnam. Through a
      retrospective survey of patients at District Tuberculosis Units (DTUs) of the
      National Tuberculosis Programme in Ho Chi Minh City, we investigated utilization
      of private and public health-care providers among people with symptoms of TB.
      Eight hundred and one patients in eight DTUs were interviewed. For the current
      illness episode, about half of the patients had initially opted for a private
      health-care provider. Twenty-seven percent had been to a private physician and
      31% to a private pharmacy at some time during their current illness. We found no
      significant association between socioeconomic status and use of private health
      care providers. Utilization of private health-care providers among people with TB
      or symptoms of TB in Ho Chi Minh City seems to be similar to the general
      utilization of private providers in Vietnam, at least before TB is diagnosed.
      Since a large proportion of people with TB in Ho Chi Minh City across all
      economic and social strata consult private providers at some time during their
      illness, planners of TB control strategies need to consider both the health-care
      seeking behaviour of people with TB and the clinical behaviour of private
      providers, in order to secure early detection of TB, early initiation of
      appropriate treatment, and maintenance of appropriate treatment.

PMID- 11238431
TI  - Health-care seeking and expenditure by young Indian mothers in the public and
      private sectors.
AB  - A total of 421 young married mothers in Karnataka State, India, were followed up
      at monthly intervals for 1 year. Results are presented on self-reported
      morbidity, treatment-seeking behaviour and health expenditures. A total of 911
      completed illness episodes were reported, of which 58% resulted in consultations
      with practitioners, mostly working in the private sector. Amongst those who did
      consult physicians, an average of 1.76 visits was made per episode. The average
      cost per visit was 46 Rupees and 38 Rupees, for private and public-sector
      consultations respectively. The overall mean annual expenditure on treatment and
      associated costs for the entire sample was 172 Rupees, of which 104 Rupees was
      spent on private-sector treatment. Poorer women reported significantly more days
      of morbidity than richer women but spent significantly less per 100 days of
      illness.

PMID- 11238432
TI  - Caesarean sections in Mexico: are there too many?
AB  - This paper seeks to quantify the magnitude of caesarean sections in Mexican
      public health-care institutions in recent years, to characterize the evolution of
      caesarean section rates (CSR) during the last decade, and to estimate the
      possible economic cost caused by the excess of caesareans performed in these
      institutions. The study is based on data obtained from the health sector, both
      for Mexico in the 5-year period 1993-97 and for the Mexican State of Jalisco
      between 1983 and 1998. Linear regression analysis was used to evaluate time
      series, and "excess of caesareans" was considered the number of caesarean
      deliveries performed above the admissible 15% CSR. The results reflect that on
      the national level, more than one-quarter of the deliveries handled by public
      institutions ended in caesarean section for each analyzed year, and if the
      deliveries performed in private institutions are included, the national rate is
      around 30%. A marked increase in CSR can be observed in Jalisco between 1983 and
      1998 (almost 50%); and the cost for the nation of this CSR excess in financial
      terms is highly significant: several millions of dollars--obtained from public
      funds--are spent annually and unnecessarily by health services. The findings
      suggest that the increase in CSR is a public health problem that has not been
      satisfactorily faced by the health sector authorities. Many unnecessary
      caesareans would undoubtedly be avoided if the policies of these public health
      care institutions were to consider, as a priority, both the known higher risk
      implicit in a caesarean for the health of the mother and child, and the economic
      impact on the country and its health institutions of the excessive number of
      caesareans performed yearly.

PMID- 11238433
TI  - The impact of media-based health education on tuberculosis diagnosis in Cali,
      Colombia.
AB  - Tuberculosis (TB) is one of the most worrying infectious diseases facing less
      developed countries. Diagnosis and treatment of those who are transmitting
      Mycobacterium tuberculosis is considered a very effective control strategy.
      Within this strategy the priority is to achieve high cure rates before attempting
      to increase case finding. However, there is a dearth of research on how to
      increase case finding and diagnostic coverage in those settings where high cure
      rates are being achieved. This paper presents an evaluation of the impact on case
      finding of a mass media health education campaign for TB control in Cali,
      Colombia. The campaign aimed at increasing case finding and reducing levels of
      prejudice against people with TB. The impact assessment shows that the campaign
      produced an increase of 64% in the number of direct smears processed by the
      laboratories and an increase of 52% in the number of new cases of positive
      pulmonary TB, with respect to the previous period. Unfortunately, the effects of
      the campaign were short-lived. These findings have at least two important
      implications. First, passive case finding is likely to be an insufficient
      strategy to reach the operational targets of diagnostic coverage. Secondly,
      providing basic information about the earliest symptoms of TB and the procedures
      for diagnosis can increase diagnostic coverage, and thus strengthen the effect on
      infection risk of control programmes with high cure rates. Further research is
      required to identify other strategies that could, first, increase diagnostic
      coverage and, secondly, make the intervention effects sustainable.

PMID- 11238434
TI  - The influence of health sector reform and external assistance in Burkina Faso.
AB  - Despite health reform and increasing public investment in the health sector,
      utilization of curative health services, immunization coverage and patient
      satisfaction with the public health care system are steadily decreasing in
      Burkina Faso. It seems that the health care system itself is "ill". This paper
      examines the major symptoms associated with this illness. The central thesis
      suggests that any further improvement of health care performance in Burkina Faso
      will be subject to profound central reform in the area of human resources and
      financial management of the sector. Such a broad reform package cannot be
      achieved through the current project approach, but a sector-wide approach (SWAp)
      does not seem to be realistic at the present time. Policy discussions at a level
      higher than the Ministry of Health could be beneficial for achieving better donor
      coordination and increasing the commitment of the Ministry of Health to a sector
      wide approach. Health sector reform issues and priorities and the role of
      international cooperation are reviewed and discussed.

PMID- 11238435
TI  - Private initiatives and policy options: recent health system experience in India.
AB  - In the recent past the impact of structural adjustment in the Indian health care
      sector has been felt in the reduction in central grants to States for public
      health and disease control programmes. This falling share of central grants has
      had a more pronounced impact on the poorer states, which have found it more
      difficult to raise local resources to compensate for this loss of revenue. With
      the continued pace of reforms, the likelihood of increasing State expenditure on
      the health care sector is limited in the future. As a result, a number of notable
      trends are appearing in the Indian health care sector. These include an
      increasing investment by non-resident Indians (NRIs) in the hospital industry,
      leading to a spurt in corporatization in the States of their original domicile
      and an increasing participation by multinational companies in diagnostics aiming
      to capture the potential of the Indian health insurance market. The policy
      responses to these private initiatives are reflected in measures comprising
      strategies to attract private sector participation and management inputs into
      primary health care centres (PHCs), privatization or semi-privatization of public
      health facilities such as non-clinical services in public hospitals, innovating
      ways to finance public health facilities through non-budgetary measures, and tax
      incentives by the State governments to encourage private sector investment in the
      health sector. Bearing in mind the vital importance of such market forces and
      policy responses in shaping the future health care scenario in India, this paper
      examines in detail both of these aspects and their implications for the Indian
      health care sector. The analysis indicates that despite the promising newly
      emerging atmosphere, there are limits to market forces; appropriate refinement in
      the role of government should be attempted to avoid undesirable consequences of
      rising costs, increasing inequity and consumer exploitation. This may require
      opening the health insurance market to multinational companies, the proper
      channelling of tax incentives to set up medical institutions in backward areas,
      and reinforcing appropriate regulatory mechanisms.

PMID- 11238436
TI  - Revolving drug funds at front-line health facilities in Vientiane, Lao PDR.
AB  - Pharmaceutical cost recovery programmes, which have been mainly implemented in
      Africa, are gradually spreading to Southeast Asian countries that formerly
      belonged to the socialist bloc. This report describes the economic and
      operational realities of revolving drug funds (RDFs) at district hospitals and
      health centres in the capital of the Lao PDR by reviewing research conducted by
      the implementing department. People in the municipality spent an average of US$11
      on drugs in 1996. The RDFs comprised only 3% of the total yearly drug sales in
      the municipality, whereas private pharmacies accounted for 75%. The RDFs were
      forced to operate in conjunction with the remaining government drug endowment and
      the thriving private pharmacies. This scheme has provided a stable supply of
      essential drugs. The assurance of drug availability at the front-line health
      facilities has resulted in increased utilization of the facilities despite the
      introduction of a drug fee. The cost recovery rate was 107% at health centres and
      108% at district hospitals in two monitored districts during the 10 months from
      November 1997. Decentralized financial management was essential for cost
      recovery, allowing timely adjustment of selling prices as purchase prices rapidly
      inflated after the Asian economic crisis. The health staff observed that the
      people perceived drugs as everyday commodities that they should buy and take
      based on self-diagnosis and personal preference. Adaptation of the public health
      authorities to market-oriented thinking along with the establishment of
      pharmaceutical cost recovery occurred with few problems. However, both financial
      and operational management capacity at the municipal level pose a major challenge
      to policy clarification and scheme setting, especially in procurement, control of
      prescribing practices and the integration of drug dispensing with other
      components of quality clinical care.

PMID- 11238437
TI  - Sexual behaviour and sexually transmitted diseases among young men in Zambia.
AB  - Sexually transmitted diseases (STDs) are an increasing public health problem in
      Zambia. About 200 000 cases of STDs are treated annually in the formal health
      sector. Young people are the most affected by STDs. High-risk sexual behaviour
      has been identified as the major risk factor for STDs among young people. We
      conducted interviews and focus group discussions with a purposely selected sample
      of 126 young men aged between 16 and 26 in Chiawa, rural Zambia. The aim of the
      interviews and focus group discussions was to explore views about sexual
      practices and attitudes towards STD. Fifty-eight (59%) young men reported having
      had pre-marital or extra-marital sexual partners during the past year. The
      maximum number was five partners for six individuals. Forty-two (43%) had pre
      marital or extra-marital sexual partners at the time of the interviews. Focus
      group discussions revealed that perceptions of manhood encouraged multiple sexual
      relationships. Twenty-two (23%) reported having suffered from an STD in the past.
      Seventy-nine (81%) said they were likely to inform their sexual partners if they
      had an STD. Although condoms were believed to give protection against STDs by the
      majority (94%), only 6% said they always used condoms. The data suggest that
      condoms were perceived to affect male potency. These results show that STDs,
      multiple sexual relationships and unprotected sex are common among the young men
      of Chiawa. Perceptions that emphasize manhood are widespread and these may
      negatively affect efforts for positive behavioural change. Health messages that
      target the young men should take into account the local perceptions and values
      that seem to sustain risky sexual behaviour.

PMID- 11238438
TI  - Cost and cost-effectiveness guidelines: which ones to use?
AB  - Given the increased awareness of the importance of cost-effectiveness in health
      care, there has been a growth in the number of published economic evaluations in
      recent years. Partly in response to concerns about deficiencies in the
      methodology of published studies, there has been a growth of interest in
      guidelines for economic evaluation. This paper reviews the various objectives of
      economic analyses, and then summarizes the existing groups of guidelines for cost
      and cost-effectiveness analyses. Finally, it compares and discusses the
      appropriate uses and limitations of the guidelines, with particular emphasis on
      those developed for applications in developing countries.

PMID- 11238439
TI  - A process of change in first-line health services in Chad.

PMID- 11238440
TI  - Operational RNA code for amino acids in relation to genetic code in evolution.

PMID- 11238441
TI  - Physical and functional interactions between Zic and Gli proteins.
AB  - Zic and Gli family proteins are transcription factors that share similar zinc
      finger domains. Recent studies indicate that Zic and Gli collaborate in neural
      and skeletal development. We provide evidence that the Zic and Gli proteins
      physically and functionally interact through their zinc finger domains. Moreover,
      Gli proteins were translocated to cell nuclei by coexpressed Zic proteins, and
      both proteins regulated each other's transcriptional activity. Our result
      suggests that the physical interaction between Zic and Gli is the molecular basis
      of their antagonistic or synergistic features in developmental contexts and that
      Zic proteins are potential modulators of the hedgehog-mediated signaling pathway.

PMID- 11238442
TI  - The Venus's-flytrap and cysteine-rich domains of the human Ca2+ receptor are not
      linked by disulfide bonds.
AB  - The extracellular N-terminal domain of the human Ca(2+) receptor (hCaR) consists
      of a Venus's-flytrap (VFT) domain and a cysteine-rich (Cys-rich) domain. We have
      shown earlier that the Cys-rich domain is critical for signal transmission from
      the VFT domain to the seven-transmembrane domain. The VFT domain contains 10
      cysteines: two of them (Cys(129) and Cys(131)) were identified as involved in
      intermolecular disulfide bonds necessary for homodimerization, and six others
      (Cys(60)-Cys(101), Cys(358)-Cys(395), and Cys(437)-Cys(449)) are predicted to
      form three intramolecular disulfide bonds. The Cys-rich domain contains nine
      cysteines, the involvement of which in disulfide bond formation has not been
      defined. In this work, we asked whether the remaining cysteines in the hCaR VFT,
      namely Cys(236) and Cys(482), form disulfide bond(s) with cysteines in the Cys
      rich domain. We constructed mutant hCaRs with a unique tobacco etch virus (TEV)
      protease recognition site inserted between the VFT domain and the Cys-rich
      domain. These mutant hCaRs remain fully functional compared with the wild type
      hCaR. After TEV protease digestion of the mutant hCaR proteins, dimers of the VFT
      were identified on Western blot under nonreducing conditions. We concluded that
      there is no disulfide bond between the VFT and the Cys-rich domains in the hCaR.

PMID- 11238443
TI  - Stress-induced inhibition of ERK1 and ERK2 by direct interaction with p38 MAP
      kinase.
AB  - We have identified a direct physical interaction between the stress signaling
      p38alpha MAP kinase and the mitogen-activated protein kinases ERK1 and ERK2 by
      affinity chromatography and coimmunoprecipitation studies. Phosphorylation and
      activation of p38alpha enhanced its interaction with ERK1/2, and this correlated
      with inhibition of ERK1/2 phosphotransferase activity. The loss of epidermal
      growth factor-induced activation and phosphorylation of ERK1/2 but not of their
      direct activator MEK1 in HeLa cells transfected with the p38alpha activator
      MKK6(E) indicated that activated p38alpha may sequester ERK1/2 and sterically
      block their phosphorylation by MEK1.

PMID- 11238444
TI  - alpha(4)-integrin mediates neutrophil-induced free radical injury to cardiac
      myocytes.
AB  - Previous work has demonstrated that circulating neutrophils (polymorphonuclear
      leukocytes [PMNs]) adhere to cardiac myocytes via beta(2)-integrins and cause
      cellular injury via the nicotinamide adenine dinucleotide phosphate (NADPH)
      oxidase enzyme system. Since PMNs induced to leave the vasculature (emigrated
      PMNs) express the alpha(4)-integrin, we asked whether (a) these PMNs also induce
      myocyte injury via NADPH oxidase; (b) beta(2)-integrins (CD18) still signal
      oxidant production, or if this process is now coupled to the alpha(4)-integrin;
      and (c) dysfunction is superoxide dependent within the myocyte or at the myocyte
      PMN interface. Emigrated PMNs exposed to cardiac myocytes quickly induced
      significant changes in myocyte function. Myocyte shortening was decreased by 30
      50% and rates of contraction and relaxation were reduced by 30% within the first
      10 min. Both alpha(4)-integrin antibody (Ab)-treated PMNs and NADPH oxidase
      deficient PMNs were unable to reduce myocyte shortening. An increased level of
      oxidative stress was detected in myocytes within 5 min of PMN adhesion. Addition
      of an anti-alpha(4)-integrin Ab, but not an anti-CD18 Ab, prevented oxidant
      production, suggesting that in emigrated PMNs the NADPH oxidase system is
      uncoupled from CD18 and can be activated via the alpha(4)-integrin. Addition of
      exogenous superoxide dismutase (SOD) inhibited all parameters of dysfunction
      measured, whereas overexpression of intracellular SOD within the myocytes did not
      inhibit the oxidative stress or the myocyte dysfunction caused by the emigrated
      PMNs. These findings demonstrate that profound molecular changes occur within
      PMNs as they emigrate, such that CD18 and associated intracellular signaling
      pathways leading to oxidant production are uncoupled and newly expressed alpha(4)
      integrin functions as the ligand that signals oxidant production. The results
      also provide pathological relevance as the emigrated PMNs have the capacity to
      injure cardiac myocytes through the alpha(4)-integrin-coupled NADPH oxidase
      pathway that can be inhibited by extracellular, but not intracellular SOD.

PMID- 11238446
TI  - A novel interaction of the Golgi complex with the vimentin intermediate filament
      cytoskeleton.
AB  - The integration of the vimentin intermediate filament (IF) cytoskeleton and
      cellular organelles in vivo is an incompletely understood process, and the
      identities of proteins participating in such events are largely unknown. Here, we
      show that the Golgi complex interacts with the vimentin IF cytoskeleton, and that
      the Golgi protein formiminotransferase cyclodeaminase (FTCD) participates in this
      interaction. We show that the peripherally associated Golgi protein FTCD binds
      directly to vimentin subunits and to polymerized vimentin filaments in vivo and
      in vitro. Expression of FTCD in cultured cells results in the formation of
      extensive FTCD-containing fibers originating from the Golgi region, and is
      paralleled by a dramatic rearrangements of the vimentin IF cytoskeleton in a
      coordinate process in which vimentin filaments and FTCD integrate into chimeric
      fibers. Formation of the FTCD fibers is obligatorily coupled to vimentin assembly
      and does not occur in vim(-/-) cells. The FTCD-mediated regulation of vimentin IF
      is not a secondary effect of changes in the microtubule or the actin
      cytoskeletons, since those cytoskeletal systems appear unaffected by FTCD
      expression. The assembly of the FTCD/vimentin fibers causes a coordinate change
      in the structure of the Golgi complex and results in Golgi fragmentation into
      individual elements that are tethered to the FTCD/vimentin fibers. The observed
      interaction of Golgi elements with vimentin filaments and the ability of FTCD to
      specifically interacts with both Golgi membrane and vimentin filaments and
      promote their association suggest that FTCD might be a candidate protein
      integrating the Golgi compartment with the IF cytoskeleton.

PMID- 11238445
TI  - Phosphatidylinositol 4,5-bisphosphate induces actin stress-fiber formation and
      inhibits membrane ruffling in CV1 cells.
AB  - Phosphatidylinositol 4,5 bisphosphate (PIP(2)) is widely implicated in
      cytoskeleton regulation, but the mechanisms by which PIP(2) effect cytoskeletal
      changes are not defined. We used recombinant adenovirus to infect CV1 cells with
      the mouse type I phosphatidylinositol phosphate 5-kinase alpha (PIP5KI), and
      identified the players that modulate the cytoskeleton in response to PIP(2)
      signaling. PIP5KI overexpression increased PIP(2) and reduced
      phosphatidylinositol 4 phosphate (PI4P) levels. It promoted robust stress-fiber
      formation in CV1 cells and blocked PDGF-induced membrane ruffling and nucleated
      actin assembly. Y-27632, a Rho-dependent serine/threonine protein kinase (ROCK)
      inhibitor, blocked stress-fiber formation and inhibited PIP(2) and PI4P synthesis
      in cells. However, Y-27632 had no effect on PIP(2) synthesis in lysates, although
      it inhibited PI4P synthesis. Thus, ROCK may regulate PIP(2) synthesis by
      controlling PI4P availability. PIP5KI overexpression decreased gelsolin,
      profilin, and capping protein binding to actin and increased that of ezrin. These
      changes can potentially account for the increased stress fiber and nonruffling
      phenotype. Our results establish the physiological role of PIP(2) in cytoskeletal
      regulation, clarify the relation between Rho, ROCK, and PIP(2) in the activation
      of stress-fiber formation, and identify the key players that modulate the actin
      cytoskeleton in response to PIP(2).

PMID- 11238447
TI  - Cofactor requirements for nuclear export of Rev response element (RRE)- and
      constitutive transport element (CTE)-containing retroviral RNAs. An unexpected
      role for actin.
AB  - Nuclear export of proteins containing leucine-rich nuclear export signals (NESs)
      is mediated by the export receptor CRM1/exportin1. However, additional protein
      factors interacting with leucine-rich NESs have been described. Here, we
      investigate human immunodeficiency virus type 1 (HIV-1) Rev-mediated nuclear
      export and Mason-Pfizer monkey virus (MPMV) constitutive transport element (CTE)
      mediated nuclear export in microinjected Xenopus laevis oocytes. We show that
      eukaryotic initiation factor 5A (eIF-5A) is essential for Rev and Rev-mediated
      viral RNA export, but not for nuclear export of CTE RNA. In vitro binding studies
      demonstrate that eIF-5A is required for efficient interaction of Rev-NES with
      CRM1/exportin1 and that eIF-5A interacts with the nucleoporins CAN/nup214,
      nup153, nup98, and nup62. Quite unexpectedly, nuclear actin was also identified
      as an eIF-5A binding protein. We show that actin is associated with the
      nucleoplasmic filaments of nuclear pore complexes and is critically involved in
      export processes. Finally, actin- and energy-dependent nuclear export of HIV-1
      Rev is reconstituted by using a novel in vitro egg extract system. In summary,
      our data provide evidence that actin plays an important functional role in
      nuclear export not only of retroviral RNAs but also of host proteins such as
      protein kinase inhibitor (PKI).

PMID- 11238448
TI  - Autocrine stimulation of human pancreatic duct-like development by soluble
      isoforms of epimorphin in vitro.
AB  - Epimorphin was recently described as a mesenchymal factor modulating
      morphogenesis of murine mammary ducts, skin, liver, and lung in vitro. In this
      study epimorphin was analyzed in a human, pancreatic adenocarcinoma cell line
      (A818-6) which develops single layer epithelial hollow spheres resembling normal
      pancreatic ductal structures in vitro. Soluble 34- and 31-kD isoforms of
      epimorphin were found in the culture supernatant of A818-6 cells. In lysates of
      A818-6 cells we detected the 34-and 31-kD isoforms and the dimers, and in lysates
      of fibroblasts the 150-kD tetramers of epimorphin additionally. A neutralizing
      monoclonal antibody against epimorphin (MC-1) efficiently blocked the development
      of hollow sphere structures from A818-6 cells. Coculture of A818-6 cells with
      fibroblasts stimulated the development of hollow sphere structures in general and
      increased differentiation in 5-6-d-old hollow spheres. A818-6 hollow sphere
      development in the presence of fibroblasts was also blocked by MC-1. In this
      novel system for human duct-like differentiation of pancreatic epithelial cells,
      we provide evidence for an autocrine and paracrine function of epimorphin as a
      major mediator for morphogenesis.

PMID- 11238449
TI  - The Golgi-associated hook3 protein is a member of a novel family of microtubule
      binding proteins.
AB  - Microtubules are central to the spatial organization of diverse membrane
      trafficking systems. Here, we report that Hook proteins constitute a novel family
      of cytosolic coiled coil proteins that bind to organelles and to microtubules.
      The conserved NH(2)-terminal domains of Hook proteins mediate attachment to
      microtubules, whereas the more divergent COOH-terminal domains mediate the
      binding to organelles. Human Hook3 bound to Golgi membranes in vitro and was
      enriched in the cis-Golgi in vivo. Unlike other cis-Golgi-associated proteins,
      however, a large fraction of Hook3 maintained its juxtanuclear localization after
      Brefeldin A treatment, indicating a Golgi-independent mechanism for Hook3
      localization. Because overexpression of Hook3 caused fragmentation of the Golgi
      complex, we propose that Hook3 participates in defining the architecture and
      localization of the mammalian Golgi complex.

PMID- 11238450
TI  - Rer1p, a retrieval receptor for endoplasmic reticulum membrane proteins, is
      dynamically localized to the Golgi apparatus by coatomer.
AB  - Rer1p, a yeast Golgi membrane protein, is required for the retrieval of a set of
      endoplasmic reticulum (ER) membrane proteins. We present the first evidence that
      Rer1p directly interacts with the transmembrane domain (TMD) of Sec12p which
      contains a retrieval signal. A green fluorescent protein (GFP) fusion of Rer1p
      rapidly cycles between the Golgi and the ER. Either a lesion of coatomer or
      deletion of the COOH-terminal tail of Rer1p causes its mislocalization to the
      vacuole. The COOH-terminal Rer1p tail interacts in vitro with a coatomer complex
      containing alpha and gamma subunits. These findings not only give the proof that
      Rer1p is a novel type of retrieval receptor recognizing the TMD in the Golgi but
      also indicate that coatomer actively regulates the function and localization of
      Rer1p.

PMID- 11238451
TI  - The localization of human cyclins B1 and B2 determines CDK1 substrate specificity
      and neither enzyme requires MEK to disassemble the Golgi apparatus.
AB  - In this paper, we show that substrate specificity is primarily conferred on human
      mitotic cyclin-dependent kinases (CDKs) by their subcellular localization. The
      difference in localization of the B-type cyclin-CDKs underlies the ability of
      cyclin B1-CDK1 to cause chromosome condensation, reorganization of the
      microtubules, and disassembly of the nuclear lamina and of the Golgi apparatus,
      while it restricts cyclin B2-CDK1 to disassembly of the Golgi apparatus. We
      identify the region of cyclin B2 responsible for its localization and show that
      this will direct cyclin B1 to the Golgi apparatus and confer upon it the more
      limited properties of cyclin B2. Equally, directing cyclin B2 to the cytoplasm
      with the NH(2) terminus of cyclin B1 confers the broader properties of cyclin B1.
      Furthermore, we show that the disassembly of the Golgi apparatus initiated by
      either mitotic cyclin-CDK complex does not require mitogen-activated protein
      kinase kinase (MEK) activity.

PMID- 11238452
TI  - Cargo of kinesin identified as JIP scaffolding proteins and associated signaling
      molecules.
AB  - The cargo that the molecular motor kinesin moves along microtubules has been
      elusive. We searched for binding partners of the COOH terminus of kinesin light
      chain, which contains tetratricopeptide repeat (TPR) motifs. Three proteins were
      found, the c-jun NH(2)-terminal kinase (JNK)-interacting proteins (JIPs) JIP-1,
      JIP-2, and JIP-3, which are scaffolding proteins for the JNK signaling pathway.
      Concentration of JIPs in nerve terminals requires kinesin, as evident from the
      analysis of JIP COOH-terminal mutants and dominant negative kinesin constructs.
      Coprecipitation experiments suggest that kinesin carries the JIP scaffolds
      preloaded with cytoplasmic (dual leucine zipper-bearing kinase) and transmembrane
      signaling molecules (the Reelin receptor, ApoER2). These results demonstrate a
      direct interaction between conventional kinesin and a cargo, indicate that motor
      proteins are linked to their membranous cargo via scaffolding proteins, and
      support a role for motor proteins in spatial regulation of signal transduction
      pathways.

PMID- 11238453
TI  - Regulation of CDC42 GTPase by proline-rich tyrosine kinase 2 interacting with
      PSGAP, a novel pleckstrin homology and Src homology 3 domain containing rhoGAP
      protein.
AB  - Proline-rich tyrosine kinase 2 (PYK2), a tyrosine kinase structurally related to
      focal adhesion kinase (FAK), is implicated in regulating cytoskeletal
      organization. However, mechanisms by which PYK2 participates in and regulates
      cytoskeletal organization remain largely unknown. Here we report identification
      of PSGAP, a novel protein that interacts with PYK2 and FAK and contains multiple
      domains including a pleckstrin homology domain, a rhoGTPase-activating protein
      domain, and a Src homology 3 domain. PYK2 interacts with PSGAP Src homology 3
      domain via the carboxyl-terminal proline-rich sequence. PSGAP is able to increase
      GTPase activity of CDC42 and RhoA in vitro and in vivo. Remarkably, PYK2, but not
      FAK, can activate CDC42 via inhibition of PSGAP-mediated GTP hydrolysis of CDC42.
      Moreover, PSGAP is localized at cell periphery in fibroblasts in a pleckstrin
      homology domain-dependent manner. Over expression of PSGAP in fibroblasts results
      in reorganization of cytoskeletal structures and changes of cellular morphology,
      which requires rhoGTPase-activating activity. Taken together, our results suggest
      that PSGAP is a signaling protein essential for PYK2 regulation of cytoskeletal
      organization via Rho family GTPases.

PMID- 11238454
TI  - Evidence for a replication function of FFA-1, the Xenopus orthologue of Werner
      syndrome protein.
AB  - DNA replication in higher eukaryotic cells occurs at a large number of discrete
      sites called replication foci. We have previously purified a protein, focus
      forming activity 1 (FFA-1), which is involved in the assembly of putative
      prereplication foci in Xenopus egg extracts. FFA-1 is the orthologue of the
      Werner syndrome gene product (WRN), a member of the RecQ helicase family. In this
      paper we show that FFA-1 colocalizes with sites of DNA synthesis and the single
      stranded DNA binding protein, replication protein A (RPA), in nuclei
      reconstituted in the egg extract. In addition, we show that two glutathione S
      transferase FFA-1 fusion proteins can inhibit DNA replication in a dominant
      negative manner. The dominant negative effect correlates with the incorporation
      of the fusion proteins into replication foci to form "hybrid foci," which are
      unable to engage in DNA replication. At the biochemical level, RPA can interact
      with FFA-1 and specifically stimulates its DNA helicase activity. However, in the
      presence of the dominant negative mutant proteins, the stimulation is prevented.
      These results provide the first direct biochemical evidence of an important role
      for FFA-1 in DNA replication.

PMID- 11238455
TI  - Regulation of antioxidant metabolism by translation initiation factor 2alpha.
AB  - Oxidative stress and highly specific decreases in glutathione (GSH) are
      associated with nerve cell death in Parkinson's disease. Using an experimental
      nerve cell model for oxidative stress and an expression cloning strategy, a gene
      involved in oxidative stress-induced programmed cell death was identified which
      both mediates the cell death program and regulates GSH levels. Two stress
      resistant clones were isolated which contain antisense gene fragments of the
      translation initiation factor (eIF)2alpha and express a low amount of eIF2alpha.
      Sensitivity is restored when the clones are transfected with full-length
      eIF2alpha; transfection of wild-type cells with the truncated eIF2alpha gene
      confers resistance. The phosphorylation of eIF2alpha also results in resistance
      to oxidative stress. In wild-type cells, oxidative stress results in rapid GSH
      depletion, a large increase in peroxide levels, and an influx of Ca(2+). In
      contrast, the resistant clones maintain high GSH levels and show no elevation in
      peroxides or Ca(2+) when stressed, and the GSH synthetic enzyme gamma-glutamyl
      cysteine synthetase (gammaGCS) is elevated. The change in gammaGCS is regulated
      by a translational mechanism. Therefore, eIF2alpha is a critical regulatory
      factor in the response of nerve cells to oxidative stress and in the control of
      the major intracellular antioxidant, GSH, and may play a central role in the many
      neurodegenerative diseases associated with oxidative stress.

PMID- 11238456
TI  - Drosophila integrin-linked kinase is required at sites of integrin adhesion to
      link the cytoskeleton to the plasma membrane.
AB  - Integrin-linked kinase (ILK) was identified by its interaction with the
      cytoplasmic tail of human beta1 integrin and previous data suggest that ILK is a
      component of diverse signaling pathways, including integrin, Wnt, and protein
      kinase B. Here we show that the absence of ILK function in Drosophila causes
      defects similar to loss of integrin adhesion, but not similar to loss of these
      signaling pathways. ILK mutations cause embryonic lethality and defects in muscle
      attachment, and clones of cells lacking ILK in the adult wing fail to adhere,
      forming wing blisters. Consistent with this, an ILK-green fluorescent protein
      fusion protein colocalizes with the position-specific integrins at sites of
      integrin function: muscle attachment sites and the basal junctions of the wing
      epithelium. Surprisingly, mutations in the kinase domain shown to inactivate the
      kinase activity of human ILK do not show any phenotype in Drosophila, suggesting
      a kinase-independent function for ILK. The muscle detachment in ILK mutants is
      associated with detachment of the actin filaments from the muscle ends, unlike
      integrin mutants, in which the primary defect is detachment of the plasma
      membrane from the extracellular matrix. Our data suggest that ILK is a component
      of the structure linking the cytoskeleton and the plasma membrane at sites of
      integrin-mediated adhesion.

PMID- 11238457
TI  - Rop GTPase-dependent dynamics of tip-localized F-actin controls tip growth in
      pollen tubes.
AB  - Tip-growing pollen tubes provide a useful model system to study polar growth.
      Although roles for tip-focused calcium gradient and tip-localized Rho-family
      GTPase in pollen tube growth is established, the existence and function of tip
      localized F-actin have been controversial. Using the green fluorescent protein
      tagged actin-binding domain of mouse talin, we found a dynamic form of tip
      localized F-actin in tobacco pollen tubes, termed short actin bundles (SABs). The
      dynamics of SABs during polar growth in pollen tubes is regulated by Rop1At, a
      Rop GTPase belonging to the Rho family. When overexpressed, Rop1At transformed
      SAB into a network of fine filaments and induced a transverse actin band behind
      the tip, leading to depolarized growth. These changes were due to ectopic Rop1At
      localization to the apical region of the plasma membrane and were suppressed by
      guanine dissociation inhibitor overexpression, which removed ectopically
      localized Rop1At. Rop GTPase-activating protein (RopGAP1) overexpression, or
      Latrunculin B treatments, also recovered normal actin organization and tip growth
      in Rop1At-overexpressing tubes. Moreover, overexpression of RopGAP1 alone
      disrupted SABs and inhibited growth. Finally, SAB oscillates and appears at the
      tip before growth. Together, these results indicate that the dynamics of tip
      actin are essential for tip growth and provide the first direct evidence to link
      Rho GTPase to actin organization in controlling cell polarity and polar growth in
      plants.

PMID- 11238458
TI  - Protein kinase C activation promotes microtubule advance in neuronal growth cones
      by increasing average microtubule growth lifetimes.
AB  - We describe a novel mechanism for protein kinase C regulation of axonal
      microtubule invasion of growth cones. Activation of PKC by phorbol esters
      resulted in a rapid, robust advance of distal microtubules (MTs) into the F-actin
      rich peripheral domain of growth cones, where they are normally excluded. In
      contrast, inhibition of PKC activity by bisindolylmaleimide and related compounds
      had no perceptible effect on growth cone motility, but completely blocked phorbol
      ester effects. Significantly, MT advance occurred despite continued retrograde F
      actin flow-a process that normally inhibits MT advance. Polymer assembly was
      necessary for PKC-mediated MT advance since it was highly sensitive to a range of
      antagonists at concentrations that specifically interfere with microtubule
      dynamics. Biochemical evidence is presented that PKC activation promotes
      formation of a highly dynamic MT pool. Direct assessment of microtubule dynamics
      and translocation using the fluorescent speckle microscopy microtubule marking
      technique indicates PKC activation results in a nearly twofold increase in the
      typical lifetime of a MT growth episode, accompanied by a 1.7-fold increase and
      twofold decrease in rescue and catastrophe frequencies, respectively. No
      significant effects on instantaneous microtubule growth, shortening, or sliding
      rates (in either anterograde or retrograde directions) were observed. MTs also
      spent a greater percentage of time undergoing retrograde transport after PKC
      activation, despite overall MT advance. These results suggest that regulation of
      MT assembly by PKC may be an important factor in determining neurite outgrowth
      and regrowth rates and may play a role in other cellular processes dependent on
      directed MT advance.

PMID- 11238459
TI  - The supramolecular organization of fibrillin-rich microfibrils.
AB  - We propose a new model for the alignment of fibrillin molecules within fibrillin
      microfibrils. Automated electron tomography was used to generate three
      dimensional microfibril reconstructions to 18.6-A resolution, which revealed many
      new organizational details of untensioned microfibrils, including heart-shaped
      beads from which two arms emerge, and interbead diameter variation. Antibody
      epitope mapping of untensioned microfibrils revealed the juxtaposition of
      epitopes at the COOH terminus and near the proline-rich region, and of two
      internal epitopes that would be 42-nm apart in unfolded molecules, which infers
      intramolecular folding. Colloidal gold binds microfibrils in the absence of
      antibody. Comparison of colloidal gold and antibody binding sites in untensioned
      microfibrils and those extended in vitro, and immunofluorescence studies of
      fibrillin deposition in cell layers, indicate conformation changes and
      intramolecular folding. Mass mapping shows that, in solution, microfibrils with
      periodicities of <70 and >140 nm are stable, but periodicities of approximately
      100 nm are rare. Microfibrils comprise two in-register filaments with a
      longitudinal symmetry axis, with eight fibrillin molecules in cross section. We
      present a model of fibrillin alignment that fits all the data and indicates that
      microfibril extensibility follows conformation-dependent maturation from an
      initial head-to-tail alignment to a stable approximately one-third staggered
      arrangement.

PMID- 11238460
TI  - A caveolin dominant negative mutant associates with lipid bodies and induces
      intracellular cholesterol imbalance.
AB  - Recent studies have indicated a role for caveolin in regulating cholesterol
      dependent signaling events. In the present study we have analyzed the role of
      caveolins in intracellular cholesterol cycling using a dominant negative caveolin
      mutant. The mutant caveolin protein, cav-3(DGV), specifically associates with the
      membrane surrounding large lipid droplets. These structures contain neutral
      lipids, and are accessed by caveolin 1-3 upon overexpression. Fluorescence,
      electron, and video microscopy observations are consistent with formation of the
      membrane-enclosed lipid rich structures by maturation of subdomains of the ER.
      The caveolin mutant causes the intracellular accumulation of free cholesterol
      (FC) in late endosomes, a decrease in surface cholesterol and a decrease in
      cholesterol efflux and synthesis. The amphiphile U18666A acts synergistically
      with cav(DGV) to increase intracellular accumulation of FC. Incubation of cells
      with oleic acid induces a significant accumulation of full-length caveolins in
      the enlarged lipid droplets. We conclude that caveolin can associate with the
      membrane surrounding lipid droplets and is a key component involved in
      intracellular cholesterol balance and lipid transport in fibroblasts.

PMID- 11238461
TI  - Accumulation of caveolin in the endoplasmic reticulum redirects the protein to
      lipid storage droplets.
AB  - Caveolin-1 is normally localized in plasma membrane caveolae and the Golgi
      apparatus in mammalian cells. We found three treatments that redirected the
      protein to lipid storage droplets, identified by staining with the lipophilic dye
      Nile red and the marker protein ADRP. Caveolin-1 was targeted to the droplets
      when linked to the ER-retrieval sequence, KKSL, generating Cav-KKSL. Cav-DeltaN2,
      an internal deletion mutant, also accumulated in the droplets, as well as in a
      Golgi-like structure. Third, incubation of cells with brefeldin A caused caveolin
      1 to accumulate in the droplets. This localization persisted after drug washout,
      showing that caveolin-1 was transported out of the droplets slowly or not at all.
      Some overexpressed caveolin-2 was also present in lipid droplets. Experimental
      reduction of cellular cholesteryl ester by 80% did not prevent targeting of Cav
      KKSL to the droplets. Cav-KKSL expression did not grossly alter cellular
      triacylglyceride or cholesteryl levels, although droplet morphology was affected
      in some cells. These data suggest that accumulation of caveolin-1 to unusually
      high levels in the ER causes targeting to lipid droplets, and that mechanisms
      must exist to ensure the rapid exit of newly synthesized caveolin-1 from the ER
      to avoid this fate.

PMID- 11238462
TI  - Caveolin-2 is targeted to lipid droplets, a new "membrane domain" in the cell.
AB  - Caveolin-1 and -2 constitute a framework of caveolae in nonmuscle cells. In the
      present study, we showed that caveolin-2, especially its beta isoform, is
      targeted to the surface of lipid droplets (LD) by immunofluorescence and
      immunoelectron microscopy, and by subcellular fractionation. Brefeldin A
      treatment induced further accumulation of caveolin-2 along with caveolin-1 in LD.
      Analysis of mouse caveolin-2 deletion mutants revealed that the central
      hydrophobic domain (residues 87-119) and the NH(2)-terminal (residues 70-86) and
      COOH-terminal (residues 120-150) hydrophilic domains are all necessary for the
      localization in LD. The NH(2)- and COOH-terminal domains appeared to be related
      to membrane binding and exit from ER, respectively, implying that caveolin-2 is
      synthesized and transported to LD as a membrane protein. In conjunction with
      recent findings that LD contain unesterified cholesterol and raft proteins, the
      result implies that the LD surface may function as a membrane domain. It also
      suggests that LD is related to trafficking of lipid molecules mediated by
      caveolins.

PMID- 11238463
TI  - Mammalian sprouty-1 and -2 are membrane-anchored phosphoprotein inhibitors of
      growth factor signaling in endothelial cells.
AB  - Growth factor-induced signaling by receptor tyrosine kinases (RTKs) plays a
      central role in embryonic development and in pathogenesis and, hence, is tightly
      controlled by several regulatory proteins. Recently, Sprouty, an inhibitor of
      Drosophila development-associated RTK signaling, has been discovered.
      Subsequently, four mammalian Sprouty homologues (Spry-1-4) have been identified.
      Here, we report the functional characterization of two of them, Spry-1 and -2, in
      endothelial cells. Overexpressed Spry-1 and -2 inhibit fibroblast growth factor-
      and vascular endothelial growth factor-induced proliferation and differentiation
      by repressing pathways leading to p42/44 mitogen-activating protein (MAP) kinase
      activation. In contrast, although epidermal growth factor-induced proliferation
      of endothelial cells was also inhibited by Spry-1 and -2, activation of p42/44
      MAP kinase was not affected. Biochemical and immunofluorescence analysis of
      endogenous and overexpressed Spry-1 and -2 reveal that both Spry-1 and -2 are
      anchored to membranes by palmitoylation and associate with caveolin-1 in
      perinuclear and vesicular structures. They are phosphorylated on serine residues
      and, upon growth factor stimulation, a subset is recruited to the leading edge of
      the plasma membrane. The data indicate that mammalian Spry-1 and -2 are membrane
      anchored proteins that negatively regulate angiogenesis-associated RTK signaling,
      possibly in a RTK-specific fashion.

PMID- 11238464
TI  - The transcription coactivator CBP is a dynamic component of the promyelocytic
      leukemia nuclear body.
AB  - The transcription coactivator and histone acetyltransferase CAMP response element
      binding protein (CBP) has been demonstrated to accumulate in promyelocytic
      leukemia (PML) bodies. We show that this accumulation is cell type specific. In
      cells where CBP does not normally accumulate in PML bodies, it can be induced to
      accumulate in PML bodies through overexpression of either CBP or Pml, but not
      Sp100. Using fluorescence recovery after photobleaching, we demonstrate that CBP
      moves rapidly into and out of PML bodies. In contrast, Pml and Sp100 are
      relatively immobile in the nucleoplasm and within PML nuclear bodies. They
      possess the characteristics expected of proteins that would play a structural
      role in the integrity of these subnuclear domains. Our results are consistent
      with CBP being a dynamic component of PML bodies and that the steady-state level
      in these structures can be modulated by Pml.

PMID- 11238465
TI  - Deletion of murine SMN exon 7 directed to skeletal muscle leads to severe
      muscular dystrophy.
AB  - Spinal muscular atrophy (SMA) is characterized by degeneration of motor neurons
      of the spinal cord associated with muscle paralysis and caused by mutations of
      the survival motor neuron gene (SMN). To determine whether SMN gene defect in
      skeletal muscle might have a role in SMA pathogenesis, deletion of murine SMN
      exon 7, the most frequent mutation found in SMA, has been restricted to skeletal
      muscle by using the Cre-loxP system. Mutant mice display ongoing muscle necrosis
      with a dystrophic phenotype leading to muscle paralysis and death. The dystrophic
      phenotype is associated with elevated levels of creatine kinase activity, Evans
      blue dye uptake into muscle fibers, reduced amount of dystrophin and upregulation
      of utrophin expression suggesting a destabilization of the sarcolemma components.
      The mutant mice will be a valuable model for elucidating the underlying
      mechanism. Moreover, our results suggest a primary involvement of skeletal muscle
      in human SMA, which may contribute to motor defect in addition to muscle
      denervation caused by the motor neuron degeneration. These data may have
      important implications for the development of therapeutic strategies in SMA.

PMID- 11238466
TI  - Equine herpesvirus protein E10 induces membrane recruitment and phosphorylation
      of its cellular homologue, bcl-10.
AB  - v-E10, a caspase recruitment domain (CARD)-containing gene product of equine
      herpesvirus 2, is the viral homologue of the bcl-10 protein whose gene was found
      to be translocated in mucosa-associated lymphoid tissue (MALT) lymphomas. v-E10
      efficiently activates the c-jun NH(2)-terminal kinase (JNK), p38 stress kinase,
      and the nuclear factor (NF)-kappaB transcriptional pathway and interacts with its
      cellular homologue, bcl-10, via a CARD-mediated interaction. Here we demonstrate
      that v-E10 contains a COOH-terminal geranylgeranylation consensus site which is
      responsible for its plasma membrane localization. Expression of v-E10 induces
      hyperphosphorylation and redistribution of bcl-10 from the cytoplasm to the
      plasma membrane, a process which is dependent on the intactness of the v-E10 CARD
      motif. Both membrane localization and a functional CARD motif are important for v
      E10-mediated NF-kappaB induction, but not for JNK activation, which instead
      requires a functional v-E10 binding site for tumor necrosis factor receptor
      associated factor (TRAF)6. Moreover, v-E10-induced NF-kappaB activation is
      inhibited by a dominant negative version of the bcl-10 binding protein TRAF1,
      suggesting that v-E10-induced membrane recruitment of cellular bcl-10 induces
      constitutive TRAF-mediated NF-kappaB activation.

PMID- 11238467
TI  - Kinesin delivers: identifying receptors for motor proteins.

PMID- 11238468
TI  - Caveolin, cholesterol, and lipid droplets?

PMID- 11238469
TI  - Clinical review 123: Anabolic therapy for osteoporosis.
AB  - All currently available, approved therapies for osteoporosis inhibit bone
      resorption. By acting at this site in the bone remodeling cycle, estrogens,
      selective estrogen receptor modulators, calcitonin, and the bisphosphonates all
      have the capacity to increase bone mineral density and to reduce the risk of new
      fractures. There can be no doubt that these agents have had an enormous impact on
      our diagnostic and therapeutic approach to osteoporosis. Despite their great
      value, the antiresorptives are generally not associated with dramatic increases
      in bone mass, and their action to reduce fracture risk, although highly
      significant, is rarely more than 50% of the baseline risk. Another approach is
      anabolic therapy, in which bone formation is directly stimulated. In this review
      we will summarize the anabolic agents that have been studied and present a
      current view of their current standing. Fluoride, GH, insulin-like growth factor
      I, the statins, and PTH will be reviewed. Although still in development,
      approaches to combination therapy with antiresorptives and anabolic agents are
      also promising.

PMID- 11238470
TI  - Clinical review 124: Diabetic dyslipidemia: causes and consequences.

PMID- 11238471
TI  - Clinical review 125: The insulin receptor and its cellular targets.
AB  - The pleiotropic actions of insulin are mediated by a single receptor tyrosine
      kinase. Structure/function relationships of the insulin receptor have been
      conclusively established, and the early steps of insulin signaling are known in
      some detail. A generally accepted paradigm is that insulin receptors, acting
      through insulin receptor substrates, stimulate the lipid kinase activity of
      phosphatidylinositol 3-kinase. The rapid rise in Tris-phosphorylated inositol
      (PIP(3)) that ensues triggers a cascade of PIP(3)-dependent serine/threonine
      kinases. Among the latter, Akt (a product of the akt protooncogene) and atypical
      protein kinase C isoforms are thought to be involved in insulin regulation of
      glucose transport and oxidation; glycogen, lipid, and protein synthesis; and
      modulation of gene expression. The presence of multiple insulin-regulated, PIP(3)
      dependent kinases is consistent with the possibility that different pathways are
      required to regulate different biological actions of insulin. Additional work
      remains to be performed to understand the distal components of insulin signaling.
      Moreover, there exists substantial evidence for insulin receptor substrate-
      and/or phosphatidylinositol 3-kinase-independent pathways of insulin action. The
      ultimate goal of these investigations is to provide clues to the pathogenesis and
      treatment of the insulin resistant state that is characteristic of type 2
      diabetes.

PMID- 11238472
TI  - Is fat intake a risk factor for fat gain in children?

PMID- 11238473
TI  - Using beta-cell growth factors to enhance human pancreatic Islet transplantation.
AB  - This is a particularly exciting time in the field of pancreatic islet growth,
      development, and survival. The recent publication of a study demonstrating that
      human pancreatic islet transplantation is both technically and immunologically
      feasible has highlighted the need for large supplies of pancreatic islets or
      pancreatic beta cells for larger-scale islet transplantation in patients with
      diabetes. This, together with a rapid expansion in the past several years of the
      understanding of mechanisms of islet growth, development, and survival, has
      accelerated and invigorated efforts to therapeutically harness the cellular
      mechanisms responsible for pancreatic beta-cell proliferation, survival, and
      development and to take advantage of this new knowledge to enhance the
      availability, survival, and function of pancreatic beta cells in human islet
      transplantation for diabetes mellitus. Here, we briefly review the confluence of
      events that have provided optimism and energy to the islet transplant field, and
      we focus on peptide growth factors that eventually may be deployed in the effort
      to augment islet mass and function in patients with diabetes.

PMID- 11238474
TI  - Pancreatic B-cell defects in gestational diabetes: implications for the
      pathogenesis and prevention of type 2 diabetes.

PMID- 11238475
TI  - Evaluation and treatment of sporadic nontoxic goiter--some answers and more
      questions.

PMID- 11238476
TI  - A randomized trial comparing levothyroxine with radioactive iodine in the
      treatment of sporadic nontoxic goiter.
AB  - A randomized clinical trial was performed in consecutive patients with sporadic
      nontoxic nodular goiter to compare efficacy and side effects of iodine-131
      ((131)I) therapy with suppressive levothyroxine (L-thyroxine) treatment. Sixty
      four patients were randomized after stratification for sex and menopausal age to
      receive (131)I (4.44 MBq/g thyroid; group A) or suppressive L-thyroxine treatment
      aiming at TSH values between 0.01 and 0.1 mU/L (group B). The main outcome
      measurements after 2 yr were goiter size by ultrasound, serum thyroid function
      tests, markers of bone turnover, and bone mineral density (BMD). Fifty-seven
      patients completed the trial. Goiter size was reduced after 2 yr by 44% in group
      A and by 1% in group B (P< 0.001). Nonresponders (goiter reduction <13%) were 1
      of 29 patients in group A and 16 of 28 patients in group B (P = 0.00001). In
      responders, goiter reduction in group A (46%) was greater than in group B (22%;
      P< 0.005). In group A, 45% of patients developed hypothyroidism. In group B, 10
      patients experienced thyrotoxic symptoms, requiring discontinuation of treatment
      in 2 (in 1 because of atrial fibrillation). Markers of bone formation and bone
      resorption increased significantly in group B, related to a mean decrease of 3.6%
      of BMD at the lumbar spine after 2 yr (from 1.09 +/- 0.22 to 1.05 +/- 0.23
      g/cm(2); P< 0.001), both in pre- and postmenopausal women. No changes in BMD were
      observed in group A. In conclusion, (131)I therapy is more effective and better
      tolerated than L-thyroxine treatment in patients with sporadic nontoxic goiter.
      Suppressive L-thyroxine treatment results in significant bone loss.

PMID- 11238477
TI  - The role of androgens in women.

PMID- 11238478
TI  - Type 1 aldosterone synthase deficiency presenting in a middle-aged man.
AB  - Aldosterone synthase deficiency due to mutations in the CYP11B2 gene usually
      presents in infancy with electrolyte abnormalities and failure to thrive, whereas
      affected adults are usually asymptomatic. We describe a patient who first came to
      medical attention in middle age when he developed hyperkalemia after preparation
      for a barium enema. Past medical history was notable for failure to thrive in
      infancy. He had elevated PRA with low serum and urinary levels of aldosterone and
      its metabolites and normal or slightly elevated levels of 18
      hydroxycorticosterone. These findings suggested a diagnosis of type 1 aldosterone
      synthase deficiency. The patient had a homozygous duplication of six nucleotides
      at codon 143 in exon 3 of CYP11B2, leading to the insertion of two amino acid
      residues (Arg-Leu). When the corresponding mutant complementary DNA was expressed
      in cultured cells, the resulting enzyme was completely inactive, confirming the
      diagnosis. We conclude that aldosterone synthase deficiency represents an unusual
      cause of hyperreninemic hypoaldosteronism presenting in adult life, but it should
      be suspected if the past medical history is positive for failure to thrive in
      childhood or if the patient manifests no other recognized causes of
      hyperreninemic hypoaldosteronism.

PMID- 11238479
TI  - Increased pulsatility, process irregularity, and nocturnal trough concentrations
      of growth hormone in amenorrheic compared to eumenorrheic athletes.
AB  - Amenorrheic athletes exhibit a spectrum of neuroendocrine disturbances, including
      alterations in the GH-insulin-like growth factor I (IGF-I) axis. Whether these
      changes are due to exercise or amenorrhea is incompletely characterized. The
      present study investigates spontaneous (overnight) and exercise-stimulated GH
      secretion and associated IGF-binding proteins (IGFBPs) in amenorrheic (AA; n =
      5), and eumenorrheic athletes ( n = 5) matched for age, percent body fat (dual
      energy x-ray absorptiometry), training history, and maximal oxygen consumption.
      Each volunteer participated in two hospital admissions consisting of a 50-min
      submaximal exercise bout (70% maximal oxygen consumption) and an 8-h nocturnal
      sampling period. Deconvolution analysis of serum GH concentration time series
      revealed increases in the half-life of GH (60%) and the number of secretory
      bursts (85%) as well as a decrease in their half-duration (50%) and the mass of
      GH secreted per pulse (300%) in the AA cohort. Time occupancy at elevated trough
      GH concentrations was significantly increased, and GH pulsatility (approximate
      entropy) was more irregular in the AA group. During exercise, AA exhibited a
      reversal of the normal relationship between IGF-I and GH, and a 4- to 5-fold
      blunting of stimulated peak and integrated GH secretion. Fasting levels of plasma
      IGF-I, IGFBP-3, and IGFBP-1 appeared to be unaffected by menstrual status. In
      ensemble, this phenotype of GH release in amenorrheic athletes suggests disrupted
      neuroregulation of episodic GH secretion, possibly reflecting decreased
      somatostinergic inhibition basally, and reduced GHRH output in response to
      exercise compared with eumenorrheic athletes. Accordingly, we postulate that the
      amenorrheic state, beyond the exercise experience per se, alters the
      neuroendocrine control of GH output in amenorrheic athletes.

PMID- 11238480
TI  - What are the physical characteristics associated with a normal metabolic profile
      despite a high level of obesity in postmenopausal women?
AB  - Although obesity is often associated with insulin resistance and a cluster of
      metabolic disturbances, the existence of a subgroup of healthy but obese
      individuals has been postulated. It is unclear why some obese individuals fail to
      show traditional risk factors associated with the insulin resistance syndrome
      despite having a very high accumulation of body fat. To address this issue, we
      identified and studied a subgroup of metabolically normal but obese (MNO)
      postmenopausal women to gain insight into potential physiological factors that
      may protect them against the development of obesity-related comorbidities. We
      carefully examined the metabolic characteristics of 43 obese, sedentary
      postmenopausal women (mean +/- SD, 58.0 +/- 6.0 yr). Subjects were classified as
      MNO or as metabolically abnormal obese (MAO) based on an accepted cut-point for
      insulin sensitivity (measured by the hyperinsulinemic/euglycemic clamp
      technique). Thereafter, we determined 1) body composition (fat mass and lean body
      mass), 2) body fat distribution (abdominal visceral and sc adipose tissue areas,
      midthigh sc adipose tissue and muscle attenuation), 3) plasma lipid-lipoprotein
      levels, 4) plasma glucose and insulin concentrations, 5) resting blood pressure,
      6) peak oxygen consumption, 7) physical activity energy expenditure, and 8) age
      related onset of obesity with a questionnaire as potential modulators of
      differences in the risk profile. We identified 17 MNO subjects who displayed high
      insulin sensitivity (11.2 +/- 2.6 mg/min.kg lean body mass) and 26 MAO subjects
      with lower insulin sensitivity (5.7 +/- 1.1 mg/min.kg lean body mass). Despite
      comparable total body fatness between groups (45.2 +/- 5.3% vs. 44.8 +/- 6.6%; P:
      = NS), MNO individuals had 49% less visceral adipose tissue than MAO subjects
      (141 +/- 53 vs. 211 +/- 85 cm(2); P: < 0.01). No difference was noted between
      groups for abdominal sc adipose tissue (453 +/- 126 vs. 442 +/- 144 cm(2); P: =
      NS), total fat mass (38.1 +/- 10.6 vs. 40.0 +/- 11.8 kg), muscle attenuation
      (42.2 +/- 2.6 vs. 43.6 +/- 4.8 Houndsfield units), and physical activity energy
      expenditure (1060 +/- 323 vs. 1045 +/- 331 Cal/day). MNO subjects had lower
      fasting plasma glucose and insulin concentrations and lower insulin levels during
      the oral glucose tolerance test (P: values ranging between 0.01-0.001). No
      difference was observed between groups for 2-h glucose levels and glucose area
      during the oral glucose tolerance test. MNO subjects showed lower plasma
      triglycerides and higher high density lipoprotein cholesterol concentrations than
      MAO individuals (P: < 0.01 in both cases). Results from the questionnaire
      indicated that 48% of the MNO women presented an early onset of obesity (<20 yr
      old) compared with 29% of the MAO subjects (P: = 0.09). Stepwise regression
      analysis showed that visceral adipose tissue and the age-related onset of obesity
      explained 22% and 13%, respectively, of the variance observed in insulin
      sensitivity (total r(2) = 0.35; P: < 0.05 in both cases). Our results support the
      existence of a subgroup of obese but metabolically normal postmenopausal women
      who display high levels of insulin sensitivity despite having a high accumulation
      of body fat. This metabolically normal profile is associated with a lower
      accumulation of visceral adipose tissue and an earlier age-related onset of
      obesity.

PMID- 11238481
TI  - Interrelationships among lipoprotein levels, sex hormones, anthropometric
      parameters, and age in hypogonadal men treated for 1 year with a permeation
      enhanced testosterone transdermal system.
AB  - Serum lipoproteins and cardiovascular risk are affected by endogenous and
      exogenous sex hormones. As part of a multicenter evaluation of a permeation
      enhanced testosterone transdermal system (TTD), the interrelationships among
      serum lipoproteins, hormone levels, anthropometric parameters, and age were
      investigated in 29 hypogonadal men. Subjects (aged 21-65 yr) were first studied
      during prior treatment with im testosterone esters (IM-T), then during an 8-week
      period of androgen withdrawal resulting in a hypogonadal state (HG), and finally
      during a 1-yr treatment period with the TTD. Compared with treatment with IM-T,
      the HG period produced increases in high density lipoprotein [HDL; 12.0 +/- 1.6%
      (+/-SEM); P<0.001] and total cholesterol (4.2 +/- 1.9%; P: = 0.02) and a decrease
      in the cholesterol/HDL ratio (-9.7 +/- 2.8%; P = 0.02). Compared with the HG
      period, TTD treatment produced decreases in HDL (-7.6 +/- 2.5%; P = 0.002) and
      increases in the cholesterol/HDL ratio (9.0 +/- 2.5%; P = 0.01) and triglycerides
      (20.7 +/- 6.4%; P: = 0.03). Small decreases in total cholesterol (-1.2 +/- 1.8%;
      P: = 0.1) and low density lipoprotein (-0.8 +/- 2.6%; P = 0.07) were also
      observed during TTD, but did not reach statistical significance. Likewise, there
      were no significant differences between the IM-T and TTD treatments. Serum HDL
      levels showed a strong negative correlation with body mass index and other
      obesity parameters in all three study periods (r < -0.45; P < 0.02). During
      treatment with TTD, serum testosterone levels also correlated negatively with
      body mass index (r = -0.621; P < 0.001). As a consequence of these relationships,
      a positive trend was observed between HDL and testosterone levels during TTD
      treatment (r = 0.336; P = 0.07). Interestingly, the changes in lipoprotein levels
      during TTD treatment indicated a more favorable profile (decrease in cholesterol
      and low density lipoprotein levels) with increasing age of the patients. In
      hypogonadal men the effects of transdermal testosterone replacement on serum
      lipoproteins appear consistent with the physiological effects of testosterone in
      eugonadal men.

PMID- 11238482
TI  - Circadian rhythms of women with fibromyalgia.
AB  - Fibromyalgia syndrome is a chronic and debilitating disorder characterized by
      widespread nonarticular musculoskeletal pain whose etiology is unknown. Many of
      the symptoms of this syndrome, including difficulty sleeping, fatigue, malaise,
      myalgias, gastrointestinal complaints, and decreased cognitive function, are
      similar to those observed in individuals whose circadian pacemaker is abnormally
      aligned with their sleep-wake schedule or with local environmental time.
      Abnormalities in melatonin and cortisol, two hormones whose secretion is strongly
      influenced by the circadian pacemaker, have been reported in women with
      fibromyalgia. We studied the circadian rhythms of 10 women with fibromyalgia and
      12 control healthy women. The protocol controlled factors known to affect markers
      of the circadian system, including light levels, posture, sleep-wake state,
      meals, and activity. The timing of the events in the protocol were calculated
      relative to the habitual sleep-wake schedule of each individual subject. Under
      these conditions, we found no significant difference between the women with
      fibromyalgia and control women in the circadian amplitude or phase of rhythms of
      melatonin, cortisol, and core body temperature. The average circadian phases
      expressed in hours posthabitual bedtime for women with and without fibromyalgia
      were 3:43 +/- 0:19 and 3:46 +/- 0:13, respectively, for melatonin; 10:13 +/- 0:23
      and 10:32 +/- 0:20, respectively for cortisol; and 5:19 +/- 0:19 and 4:57 +/-
      0:33, respectively, for core body temperature phases. Both groups of women had
      similar circadian rhythms in self-reported alertness. Although pain and stiffness
      were significantly increased in women with fibromyalgia compared with healthy
      women, there were no circadian rhythms in either parameter. We suggest that
      abnormalities in circadian rhythmicity are not a primary cause of fibromyalgia or
      its symptoms.

PMID- 11238483
TI  - Effect of protein ingestion on the glucose appearance rate in people with type 2
      diabetes.
AB  - Amino acids derived from ingested protein are potential substrates for
      gluconeogenesis. However, several laboratories have reported that protein
      ingestion does not result in an increase in the circulating glucose concentration
      in people with or without type 2 diabetes. The reason for this has remained
      unclear. In people without diabetes it seems to be due to less glucose being
      produced and entering the circulation than the calculated theoretical amount.
      Therefore, we were interested in determining whether this also was the case in
      people with type 2 diabetes. Ten male subjects with untreated type 2 diabetes
      were given, in random sequence, 50 g protein in the form of very lean beef or
      only water at 0800 h and studied over the subsequent 8 h. Protein ingestion
      resulted in an increase in circulating insulin, C-peptide, glucagon, alpha amino
      and urea nitrogen, and triglycerides; a decrease in nonesterified fatty acids;
      and a modest increase in respiratory quotient. The total amount of protein
      deaminated and the amino groups incorporated into urea was calculated to be
      approximately 20-23 g. The net amount of glucose estimated to be produced, based
      on the quantity of amino acids deaminated, was approximately 11-13 g. However,
      the amount of glucose appearing in the circulation was only approximately 2 g.
      The peripheral plasma glucose concentration decreased by approximately 1 mM after
      ingestion of either protein or water, confirming that ingested protein does not
      result in a net increase in glucose concentration, and results in only a modest
      increase in the rate of glucose disappearance.

PMID- 11238484
TI  - The spectrum and significance of primary hypophysitis.
AB  - Hypophysitis can present clinically as a mass lesion of the sella turcica.
      Secondary hypophysitis occurs in cases where a definite etiologic agent or
      process inciting the inflammatory reaction can be identified. In contrast,
      primary hypophysitis refers to inflammation confined to the pituitary gland with
      no identifiable etiologic associations. We report three cases of primary
      hypophysitis to illustrate the spectrum of three clinicopathological entities
      that encompass this disease: lymphocytic hypophysitis, granulomatous
      hypophysitis, and xanthomatous hypophysitis. Our three patients underwent
      surgery, with variable response. However, conservative, supportive treatment with
      or without surgical decompression is generally favored over aggressive and
      extensive surgical resection that results in hypopituitarism. We conclude that
      the optimal management of patients with hyophysitis requires a high index of
      suspicion before extensive surgical resection. Histological confirmation of the
      diagnosis of hypophysitis can be obtained by performing a biopsy or by requesting
      an intraoperative frozen section consultation.

PMID- 11238485
TI  - Usefulness of thyrotropin (TSH)-releasing hormone test and nocturnal surge of TSH
      for diagnosis of isolated deficit of TSH secretion.
AB  - Six patients with idiopathic isolated deficit of TSH secretion were examined and
      reported on. Their clinical symptoms and routine biochemical data were unclear
      and were not specific for hypothyroidism. Serum triiodothyronine, free thyroxine
      and TSH levels were slightly low or low-normal. Basal metabolic rate and
      thyroidal (123)I-uptake were also slightly low or low-normal. The response of
      serum TSH to TRH stimulation was blunted in all patients. No nocturnal surge of
      serum TSH level could be seen in any of the patients. Empty sella was revealed in
      three patients, and pituitary microadenoma in one patient via magnetic resolution
      imaging. Antihuman pituitary cytosol antibody was seen in five patients.
      Autoimmunity may have played a role in the pathogenesis of idiopathic isolated
      TSH deficiency. Routine examination of thyroid function cannot easily detect this
      disease. TSH response to TRH stimulation and nocturnal surge of TSH should be
      examined when this disease is suspected.

PMID- 11238486
TI  - Cardiac mass and function, carotid artery intima-media thickness, and lipoprotein
      levels in growth hormone-deficient adolescents.
AB  - The objective of our study was to evaluate whether cardiac mass and function,
      carotid artery intima-media thickness, and serum lipid and lipoprotein(a) levels
      are abnormal in adolescents with GH deficiency. Young adults with childhood-onset
      and adulthood-onset GH deficiency have been found to have a higher cardiovascular
      risk, as manifested among other factors by reduced left ventricular mass,
      impaired systolic function, significant increase in arterial intima-media
      thickness, and dyslipidemia. Twelve adolescents (seven males and five females)
      with GH deficiency (10 idiopathic and 2 organic), with an age of 14.2 +/- 2.8 yr
      and a height of 140.6 +/- 17.9 cm (height SD score, -2.6 +/- 0.3), were studied.
      Six children had received GH in the past but were off therapy for several years,
      whereas six patients had never been treated with GH. Fasting blood samples were
      obtained for serum lipids and lipoprotein(a) analysis. Patients underwent
      transthoracic M-mode and two-dimensional echocardiographic evaluation for
      measurement of interventricular septal thickness, left ventricular posterior wall
      thickness, and left ventricular mass, as well as left ventricular ejection
      fraction at rest and pulmonary venous flow velocities; carotid artery intima
      media thickness was measured using high-resolution mode B ultrasound. Seven GH
      deficient (GHD) adolescents on GH at the time of the study and 19 healthy
      adolescents, all comparable for age, pubertal status, height, weight, blood
      pressure, and pulse, participated in this study as controls. Interventricular
      septal thickness (6.5 +/- 1.3 vs. 7.0 +/- 1.5 mm), left ventricular posterior
      wall thickness (7.0 +/- 1.8 vs. 7.5 +/- 2.0 mm), and left ventricular mass after
      correction for body surface area (71.2 +/- 21.8 vs. 70.7 +/- 18.0 g/m(2)) were
      similar in untreated GHD patients and healthy controls. Similarly, the left
      ventricular ejection fraction at rest was similar in untreated GHD subjects and
      controls (70.0 +/- 0.7 vs. 70.0 +/- 0.6%), as were the pulmonary venous flow
      velocities (0.54 +/- 0.16 vs. 0.55 +/- 0.10 m/s for diastolic peak velocity; 0.51
      +/- 0.16 vs. 0.50 +/- 0.09 m/s for systolic peak velocity; and 0.19 +/- 0.06 vs.
      0.19 +/- 0.05 m/s for atrial reversal filling). Carotid artery intima-media
      thickness (0.60 +/- 0.02 mm and 0.59 +/- 0.02 mm for the right and left carotid
      arteries, respectively) was also normal in our untreated GHD patients when
      compared with healthy controls. In addition, all echocardiographic measurements
      were similar in GHD subjects on or off GH at the time of the study. Low-density
      lipoprotein cholesterol levels were increased in untreated GHD patients when
      compared with healthy controls (3.17 +/- 0.70 vs. 2.33 +/- 0.36 mmol/L; P <
      0.01), whereas total cholesterol, high-density lipoprotein cholesterol, and
      triglyceride concentrations were similar to that of controls. Total cholesterol
      levels were increased in our untreated GHD adolescents when compared with GHD
      subjects receiving GH therapy at the time of the study, while low-density
      lipoprotein cholesterol and triglyceride levels were also elevated, although not
      significantly. Lipoprotein(a) levels were elevated in untreated GHD adolescents
      when compared with healthy controls, and untreated GHD subjects had higher
      lipoprotein(a) concentrations than GH-treated patients. GHD adolescents,
      regardless of whether or not they received GH therapy, do not seem to show
      alterations in cardiac mass and function or early atherosclerotic changes. They
      must, however, be followed carefully because they already present cardiovascular
      risk factors such as dyslipidemia, which may increase their cardiovascular
      morbidity over time.

PMID- 11238487
TI  - Comparison of adrenal vein sampling and computed tomography in the
      differentiation of primary aldosteronism.
AB  - Determination of the etiology of primary aldosteronism remains a diagnostic
      challenge. The most common types of primary aldosteronism are bilateral adrenal
      hyperplasia (BAH), aldosterone-producing adenomas (APA), and primary adrenal
      hyperplasia. Computed tomography (CT) and adrenal vein sampling (AVS) are the
      primary modalities used to differentiate these subtypes. The purpose of this
      study was to compare AVS and CT imaging of the adrenal glands in patients with
      hyperaldosteronism in whom CT imaging was normal or in whom focal unilateral or
      bilateral adrenal abnormalities were detected. The diagnosis of primary
      aldosteronism was made in 62 patients based on an elevated plasma aldosterone to
      PRA ratio and an elevated urinary aldosterone excretion rate. Thirty-eight
      patients had CT imaging and successful bilateral adrenal vein sampling and were
      included in the final analysis. AVS was considered the gold standard in
      determining the specific subtype of primary aldosteronism. There were 15 patients
      with APA, 21 patients with BAH, and 2 patients with primary adrenal hyperplasia.
      Plasma aldosterone was significantly higher in patients with APA (46.3 +/- 8.5
      ng/dL; 1284 +/- 235 pmol/L) than in those with BAH (29.3 +/- 2.4 ng/dL; 813 +/-
      11 pmol/L; P < 0.05). Plasma potassium was significantly lower in patients with
      APA (3.1 +/- 0.1 mmol/L) than in patients with BAH (3.5 +/- 0.1 mmol/L; P <
      0.02). There was considerable overlap in the other biochemical indices (e.g. PRA
      and urinary aldosterone) in patients with the different subtypes. In patients
      with APA proven by AVS, eight had concordant findings with CT imaging, four had
      discordant findings, and three had normal CT imaging. In patients with BAH proven
      by AVS, four had concordant findings with CT imaging, eight had discordant
      findings, and nine had normal CT imaging. Compared with AVS, CT imaging was
      either inaccurate or provided no additional information in 68% of the patients
      with primary aldosteronism. We conclude that adrenal CT imaging is not a reliable
      method to differentiate primary aldosteronism. Adrenal vein sampling is essential
      to establish the correct diagnosis of primary aldosteronism.

PMID- 11238488
TI  - Estrogen promotes growth of human thyroid tumor cells by different molecular
      mechanisms.
AB  - Thyroid tumors are about 3 times more frequent in females than in males.
      Epidemiological studies suggest that the use of estrogens may contribute to the
      pathogenesis of thyroid tumors. In a very recent study a direct growth
      stimulatory effect of 17beta-estradiol was demonstrated in FRTL-5 rat thyroid
      cells. In this work the presence of estrogen receptors alpha and beta in thyroid
      cells derived from human goiter nodules and in human thyroid carcinoma cell line
      HTC-TSHr was demonstrated. There was no difference between the expression levels
      of estrogen receptor alpha in males and females, but there was a significant
      increase in expression levels in response to 17beta-estradiol. Stimulation of
      benign and malignant thyroid cells with 17beta-estradiol resulted in an increased
      proliferation rate and an enhanced expression of cyclin D1 protein, which plays a
      key role in the regulation of G(1)/S transition in the cell cycle. In malignant
      tumor cells maximal cyclin D1 expression was observed after 3 h, whereas in
      benign cells the effect of 17beta-estradiol was delayed. ICI 182780, a pure
      estrogen antagonist, prevented the effects of 17beta-estradiol. In addition,
      17beta-estradiol was found to modulate activation of mitogen-activated protein
      (MAP) kinase, whose activity is mainly regulated by growth factors in thyroid
      carcinoma cells. In response to 17beta-estradiol, both MAP kinase isozymes,
      extracellular signal-regulated protein kinases 1 and 2, were strongly
      phosphorylated in benign and malignant thyroid cells. Treatment of the cells with
      17beta-estradiol and MAP kinase kinase 1 inhibitor, PD 098059, prevented the
      accumulation of cyclin D1 and estrogen-mediated mitogenesis. Our data indicate
      that 17beta-estradiol is a potent mitogen for benign and malignant thyroid tumor
      cells and that it exerts a growth-promoting effect not only by binding to nuclear
      estrogen receptors, but also by activation of the MAP kinase pathway.

PMID- 11238489
TI  - The BB-paraoxonase genotype is associated with impaired brachial reactivity after
      acute hypertriglyceridemia in healthy subjects.
AB  - The possible relationship between paraoxonase (PON) gene polymorphism and
      brachial reactivity in healthy adult subjects in the presence of acute
      hypertriglyceridemia (HT), as a prooxidant factor, was investigated. In 101
      healthy subjects the response to flow- induced vasodilatation was measured before
      and after Intralipid infusion. In the same subjects the A/B PON polymorphism was
      detected. The frequency was 0.545 for AA genotype, 0.356 for the AB genotype, and
      0.099 for the BB genotype. At baseline all genotype groups had a similar increase
      in brachial artery diameter and flow. After Intralipid infusion, subjects sharing
      the BB genotype had a significant decrease vs. baseline values in changes in
      brachial artery diameter (P for trend < 0.001 vs. the other genotypes), but not
      in flow. In a subgroup of 55 subjects distributed among the 3 PON genotypes the
      same study protocol was repeated by buccal nitroglycerine administration to study
      the endothelium-independent vasodilatation. Again, subjects with the BB genotype
      had the worse vasodilation (P for trend < 0.001). Furthermore, subjects sharing
      the BB genotype had the lowest endothelium-independent and -dependent changes in
      diameter (P for trend < 0.001 vs. the other genotypes) independently of gender
      ratio, basal plasma triglycerides concentrations, and changes in plasma
      triglycerides concentrations. In conclusion, our study demonstrates that
      transient HT decreases vascular reactivity more in subjects with the PON BB
      genotype than in those with the other PON genotypes.

PMID- 11238490
TI  - Identification of the etiology of primary aldosteronism with adrenal vein
      sampling in patients with equivocal computed tomography and magnetic resonance
      findings: results in 104 consecutive cases.
AB  - The objectives of this study were to investigate the usefulness of adrenal vein
      sampling in identifying the etiology of primary aldosteronism (PA) in patients
      with equivocal CT and MR findings. Between 1990 and 1999, 104 referred
      hypertensive patients (45 women and 59 men, aged 49.6 +/- 11.6 yr) were diagnosed
      to have PA with inconclusive computed tomography scan and magnetic resonance
      results, based on established criteria. Adrenal vein sampling (AVS) for
      measurement of plasma aldosterone (A) and cortisol (C) levels was performed in
      all. Selectivity of AVS was assessed by the ratio between C levels in each
      adrenal vein and in the infrarenal inferior vena cava plasma (C(side)/C(IVC)). A
      receiver operator characteristics analysis was carried out to establish 1) the
      best AVS-derived index, 2) the degree of selectivity that could provide an
      accurate diagnosis, and 3) whether a correct diagnosis could be made from a
      unilaterally selective AVS. An aldosterone-producing adenoma (average diameter,
      12.2 +/- 0.08 mm) was eventually diagnosed in 41 patients (39.4%) and was
      excluded in the rest. Adrenal vein rupture leading to partial adrenal loss
      occurred in 1 patient (0.9% complication rate). By assuming a cut-off value of
      C(side)/C(IVC) > or = 1.1, AVS was selective in 85.7% and 94.1% of cases on the
      right and left sides, respectively, and bilaterally in 80.6% of cases. Of all AVS
      derived indexes, the A/C of one over the A/C contralateral side
      [(A/C)(side)/(A/C)(contralateral side)] furnished the best diagnostic accuracy.
      With a bilaterally selective AVS, a value of (A/C)(side)/(A/C)(contralateral
      side) > or = 2 provided a conclusive etiological diagnosis of PA in 79.7% of
      cases. At variance, no accurate diagnosis could be made from unilaterally
      selective AVS. AVS was feasible and safe in most PA patients with inconclusive
      computed tomography and magnetic resonance scans. When bilaterally selective
      (i.e. C(side)/C(IVC) > or = 1.1) a ratio of (A/C)(side)/(A/C)(control) > or = 2
      provided the best compromise of sensitivity and false positive rate for
      lateralization of the etiology of PA.

PMID- 11238492
TI  - Endogenous sex hormone levels in postmenopausal women with Alzheimer's disease.
AB  - A cross-sectional study examined whether there was a difference in endogenous
      serum sex hormone levels between community-dwelling postmenopausal women with
      Alzheimer's disease (AD) and healthy controls. Total morning levels of serum
      estrone, estradiol, androstenedione, testosterone, and cortisol were measured in
      52 nondepressed women with AD and 60 postmenopausal women who were neither
      depressed nor cognitively impaired. Estradiol was undetectable in 35.7% of cases,
      but detectable hormone was found in 96-100% of cases otherwise. After adjustment
      for potential confounds, serum levels were significantly higher for estrone (P =
      0.0057) and androstenedione (P = 0.02), but not testosterone (P = 0.086) or
      estradiol (P = 0.59), in subjects with AD. Sex hormone levels did not correlate
      with cognitive scores in either group. Although the failure to detect estradiol
      in a third of cases limits the conclusions that can be drawn for this hormone,
      the possibility that AD is associated with abnormalities in certain serum sex
      hormone levels should be considered and warrants further research.

PMID- 11238491
TI  - Diagnostic value of the acid-labile subunit in acromegaly: evaluation in
      comparison with insulin-like growth factor (IGF) I, and IGF-binding protein-1, 
      2, and -3.
AB  - In normal subjects the main form of circulating insulin-like growth factor (IGF)
      is the 150-kDa complex. This complex is formed by the IGF peptide, the acid
      stable IGF-binding protein-3 (IGFBP-3), and the acid-labile subunit (ALS).
      Experimental and clinical data have demonstrated that ALS is primarily under the
      control of GH and plays a critical role in maintaining constant levels of
      circulating IGF-I. In this study we evaluated ALS, IGF-I, and IGFBP-1, -2, and -3
      in 45 acromegalic patients in basal conditions and, in 37 of these, twice after
      surgical therapy compared with 100 age- and sex-matched control subjects to
      estimate their value as parameter of GH secretory state. The results demonstrated
      that in acromegaly before treatment all parameters (ALS, 523 +/- 26; IGF-I, 129
      +/- 6; IGFBP-1, 0.7 +/- 0.1; IGFBP-3, 234 +/- 21; nmol/L; mean +/- SEM) but IGFBP
      2 were significantly different (P<0.0001) from those in healthy subjects (ALS,
      281 +/- 4; IGF-I, 22 +/- 1; IGFBP-1, 1.6 +/- 0.1; IGFBP-3, 91 +/- 3). IGF-I was
      more sensitive (100%) than ALS (89%), and both were more predictive of disease
      status than IGFBP-3, in that 27% of the patients had IGFBP-3 levels within the
      normal range. Considering the ALS/IGFBP-3 molar ratio, almost 55% of ALS
      circulated in a free form in active acromegaly. Before treatment, the IGF
      I/IGFBPs (-1 + -2 + -3) molar ratio, which can be regarded as free, biologically
      active, IGF-I, was greatly increased (0.77 +/- 0.06; P<0.0001) compared with that
      in control subjects (0.23 +/- 0.01). After surgery, all 10 patients with
      controlled disease showed normalization of ALS (100% sensitivity), whereas 9 of
      them had normal IGFBP-3; reevaluation after varying lengths of time showed all
      these parameters within the normal range. In the 27 patients with active disease,
      IGF-I and ALS were more predictive of disease status (91% and 83% negative
      predictive values, respectively) than IGFBP-3 (53%). The basal ALS concentration
      correlated only with IGFBP-3 (r = 0.70; P<0.001). In postsurgery samples (first
      control) a statistically significant (P<0.001) correlation was found between mean
      GH values as well as minimum GH after oral glucose tolerance test and ALS (r =
      0.72 and 0.83, respectively), IGF-I (r = 0.69 and 0.77), IGFBP-3 (r = 0.50 and
      0.72), and IGFBP-2 (r = -0.36 and -0.63). Similarly, IGF-I, IGFBP-3, and ALS were
      positively correlated among themselves and negatively correlated with IGFBP-2
      (P<0.001). In conclusion, in the diagnosis of acromegaly, the measurement of
      total IGF-I appears to be the most sensitive parameter among the subunits of the
      150K complex, and IGFBP-3 the least sensitive. For ALS, this subunit is quite
      sensitive and appears to be a useful parameter in reassessment after surgical
      treatment.

PMID- 11238493
TI  - Genotype-phenotype correlations in hereditary medullary thyroid carcinoma:
      oncological features and biochemical properties.
AB  - In hereditary medullary thyroid carcinoma (MTC), few genotype-phenotype
      correlations have been established. RET genotypes (exons 10, 11, 13, and 14) of
      63 patients with hereditary MTC (from November 1994 to October 1999) were
      correlated with age at diagnosis, sex, the TNM system, and basal calcitonin
      levels. Mutations in exons 10, 11, 13, and 14 were demonstrated in 22% (14 of
      63), 54% (34 of 63), 21% (13 of 63), and 3% (2 of 63). The median ages at
      diagnosis differed significantly (38, 27, 52, and 62 yr; P = 0.003). When grouped
      by cysteine codons (exons 10 and 11 vs. exons 13 and 14), this difference became
      even more evident (30 vs. 56 yr; P = 0.001). Apart from age at diagnosis, no
      other significant associations were noted. Based hereon, three MTC risk groups
      were devised according to genotype: a high risk group (codons 634 and 618) with
      the youngest ages of 3 and 7 yr at diagnosis; an intermediate risk group (codons
      790, 620, and 611) with ages of 12, 34, and 42 yr; and a low risk group (codons
      768 and 804) with ages of 47 and 60 yr, respectively. Age at diagnosis was
      unrelated to specific nucleotide and amino acid exchange within each codon. The
      current data demonstrate that there is a significant genotype-phenotype
      correlation, allowing for a more individualized approach to the timing and extent
      of prophylactic surgery.

PMID- 11238494
TI  - Effect of levothyroxine on cardiac function and structure in subclinical
      hypothyroidism: a double blind, placebo-controlled study.
AB  - Subclinical hypothyroidism (sHT) affects 5-15% of the general population;
      however, the need of lifelong L-T(4) therapy is still controversial. As
      myocardium is a main target of thyroid hormone action, we investigated whether
      sHT induces cardiovascular alterations. Twenty sHT patients were randomly
      assigned to receive placebo or L-T(4) therapy and were followed for 1 yr. Twenty
      sex- and age-matched normal subjects served as controls. Doppler echocardiography
      and videodensitometric analysis were performed in all subjects. Myocardium
      textural parameters were obtained as mean gray levels, which were then used to
      calculate the cyclic variation index (CVI; percent systolic/diastolic change in
      mean gray levels). Patients had a significantly higher isovolumic relaxation time
      (3.1 +/- 0.5 vs. 2.6 +/- 0.6; P < 0.03), peak A (0.77 +/- 0.16 vs. 0.56 +/- 0.13
      m/s; P < 0.01), and preejection/ejection time (PEP/ET) ratio (0.72 +/- 0.05 vs.
      0.57 +/- 0.06; P < 0.03) and a lower CVI (P < 0.0001) than controls. CVI was
      inversely related to TSH level (P < 0.0001) and PEP/ET ratio (P < 0.01). L-T(4)
      treated patients showed a significant reduction of the PEP/ET ratio (P < 0.05),
      peak A (P < 0.05), and isovolumic relaxation time (P < 0.05) along with a
      normalization of CVI. Conversely, no changes were observed in the placebo-treated
      group. In conclusion, sHT affects both myocardial structure and contractility.
      These alterations may be reversed by L-T(4) therapy.

PMID- 11238495
TI  - Effect of alendronate and MK-677 (a growth hormone secretagogue), individually
      and in combination, on markers of bone turnover and bone mineral density in
      postmenopausal osteoporotic women.
AB  - GH increases bone turnover and stimulates osteoblast activity. We hypothesized
      that administration of MK-677, an orally active GH secretagogue, together with
      alendronate, a potent inhibitor of bone resorption, would maintain a higher bone
      formation rate relative to that seen with alendronate alone, thereby generating
      greater enhancement of bone mineral density (BMD) in women with postmenopausal
      osteoporosis. We determined the individual and combined effects of MK-677 and
      alendronate administration on insulin-like growth factor I levels and biochemical
      markers of bone formation (osteocalcin and bone-specific alkaline phosphatase)
      and resorption [urinary N-telopeptide cross-links (NTx)] for 12 months and BMD
      for 18 months. In a multicenter, randomized, double blind, placebo-controlled, 18
      month study, 292 women (64-85 yr old) with low femoral neck BMD were randomly
      assigned in a 3:3:1:1 ratio to 1 of 4 daily treatment groups for 12 months: MK
      677 (25 mg) plus alendronate (10 mg); alendronate (10 mg); MK-677 (25 mg); or a
      double dummy placebo. Patients who received MK-677 alone or placebo through month
      12 received MK-677 (25 mg) plus alendronate (10 mg) from months 12-18. All other
      patients remained on their assigned therapy. All patients received 500 mg/day
      calcium. The primary results, except for BMD, are provided for month 12. MK-677,
      with or without alendronate, increased insulin-like growth factor I levels from
      baseline (39% and 45%; P < 0.05 vs. placebo). MK-677 increased osteocalcin and
      urinary NTx by 22% and 41%, on the average, respectively (P < 0.05 vs. placebo).
      MK-677 and alendronate mitigated the reduction in bone formation compared with
      alendronate alone based on mean relative changes in serum osteocalcin (-40% vs. 
      54%; P < 0.05, combination vs. alendronate) and reduced the effect of alendronate
      on resorption (NTx) as well (-52% vs. -61%; P < 0.05, combination vs.
      alendronate). MK-677 plus alendronate increased BMD at the femoral neck (4.2% vs.
      2.5% for alendronate; P < 0.05). However, similar enhancement was not seen with
      MK-677 plus alendronate in BMD of the lumbar spine, total hip, or total body
      compared with alendronate alone. GH-mediated side effects were noted in the
      groups receiving MK-677, although adverse events resulting in discontinuation
      from the study were relatively infrequent. In conclusion, the anabolic effect of
      GH, as produced through the GH secretagogue MK-677, attenuated the indirect
      suppressive effect of alendronate on bone formation, but did not translate into
      significant increases in BMD at sites other than the femoral neck. Although the
      femoral neck is an important site for fracture prevention, the lack of
      enhancement in bone mass at other sites compared with that seen with alendronate
      alone is a concern when weighed against the potential side effects of enhanced GH
      secretion.

PMID- 11238496
TI  - Insulin reduction with metformin increases luteal phase serum glycodelin and
      insulin-like growth factor-binding protein 1 concentrations and enhances uterine
      vascularity and blood flow in the polycystic ovary syndrome.
AB  - We hypothesized that hyperinsulinemia contributes to early pregnancy loss in the
      polycystic ovary syndrome by adversely affecting endometrial function and
      environment. Serum glycodelin, a putative biomarker of endometrial function, is
      decreased in women with early pregnancy loss. Insulin-like growth factor-binding
      protein-1 may also play an important role in pregnancy by facilitating adhesion
      processes at the feto-maternal interface. We studied 48 women with polycystic
      ovary syndrome before and after 4 weeks of administration of 500 mg metformin (n
      = 26) or placebo (n = 22) 3 times daily. Oral glucose tolerance tests were
      performed, and serum glycodelin and insulin-like growth factor-binding protein-1
      were measured during the follicular and clomiphene-induced luteal phases of
      menses. In the metformin group, the mean (+/-SE) area under the serum insulin
      curve after glucose administration decreased from 62 +/- 6 to 19 +/- 2 nmol/L.min
      (P < 0.001). Follicular phase serum glycodelin concentrations increased 20-fold
      from 150 +/- 46 to 2813 +/- 1192 pmol/L (P < 0.001), and serum insulin-like
      growth factor-binding protein-1 concentrations increased from 936 +/- 152 to 2396
      +/- 300 pmol/L (P < 0.001). Similarly, luteal phase serum glycodelin
      concentrations increased 3-fold from 3434 +/- 1299 to 10624 +/- 1803 pmol/L (P <
      0.001), and serum insulin-like growth factor-binding protein-1 concentrations
      increased from 1220 +/- 136 to 4916 +/- 596 pmol/L (P < 0.001). Uterine vascular
      penetration also increased in the metformin group, as did blood flow of spiral
      arteries, as demonstrated by a 20% decrease in the resistance index from 0.71 +/-
      0.02 to 0.57 +/- 0.03 (P < 0.001). These variables did not change in the placebo
      group. We conclude that insulin reduction with metformin increases follicular and
      luteal phase serum glycodelin and insulin-like growth factor-binding protein-1
      concentrations and enhances luteal phase uterine vascularity and blood flow in
      the polycystic ovary syndrome. These changes may reflect an improved endometrial
      milieu for the establishment and maintenance of pregnancy.

PMID- 11238497
TI  - Disruption of the nocturnal testosterone rhythm by sleep fragmentation in normal
      men.
AB  - Recently, we have demonstrated that in normal men the nocturnal testosterone rise
      antedated the first rapid eye movement (REM) sleep episode by about 90 min and
      was correlated with REM latency. To further elucidate whether the diurnal
      testosterone rhythm is a sleep-related phenomenon or controlled by the circadian
      clock, we determined serum testosterone levels in 10 men during the ultrashort
      7/13 sleep-wake cycle paradigm. Using this schedule, subjects experienced partial
      sleep deprivation and fragmented sleep for a 24-h period. Serum testosterone
      levels were determined every 20 min between 1900-0700 h with simultaneous sleep
      recordings during the 7-min sleep attempts. The results were compared with those
      obtained in men during continuous sleep. Although mean levels and area under the
      curve of testosterone were similar in both groups, fragmented sleep resulted in a
      significant delay in testosterone rise (03:24 h +/- 1:13 vs. 22:35 h +/- 0:22).
      During fragmented sleep, nocturnal testosterone rise was observed only in
      subjects who showed REM episodes (4/10). Our findings indicate that the sleep
      related rise in serum testosterone levels is linked with the appearance of first
      REM sleep. Fragmented sleep disrupted the testosterone rhythm with a considerable
      attenuation of the nocturnal rise only in subjects who did not show REM sleep.

PMID- 11238498
TI  - The effects of transdermal estradiol in combination with oral norethisterone on
      lipoproteins, coagulation, and endothelial markers in postmenopausal women with
      type 2 diabetes: a randomized, placebo-controlled study.
AB  - People with type 2 diabetes have a substantially increased risk of coronary heart
      disease (CHD). Short-term studies with unopposed oral estradiol in women with
      diabetes have suggested potentially beneficial effects on lipids, thrombotic
      factors, and insulin sensitivity. However, most (nonhysterectomized)
      postmenopausal women require combined estrogen-progesterone preparations. We
      randomized 43 women with type 2 diabetes either to continuous transdermal
      estradiol (80-microg patches) in combination with oral norethisterone (1 mg
      daily) or to identical placebos. Blood samples were taken before and after 6
      months for measurement of lipoproteins, coagulation factors, and endothelial
      markers. Total cholesterol and triglyceride concentrations decreased by 8% and
      22%, respectively, in those receiving hormone replacement therapy (P < 0.05
      relative to change in placebo group after adjustment for baseline
      concentrations). There was a trend toward a reduction in high density lipoprotein
      cholesterol concentration (P = 0.06). Factor VII activity decreased by 16% (P <
      0.001), and von Willebrand factor antigen decreased by 7% (P = 0.014) with active
      treatment. Levels of fibrinogen, tissue plasminogen activator, fibrin D dimer,
      very low density lipoprotein cholesterol, low density lipoprotein cholesterol,
      lipoprotein(a), and leptin were not significantly altered. No change in glycemic
      control was detected. Overall, lipid changes may be considered slightly
      beneficial with respect to CHD risk. The significant decrease in factor VII
      activity in this study is notable, because elevated factor VII activity has been
      associated with an increased risk of coronary thrombosis and normally increases
      with administration of oral estrogen-containing preparations. In addition, a
      reduction in von Willebrand factor antigen is consistent with an improvement in
      endothelial function. We suggest that the regimen used in this study may have the
      potential to reduce CHD risk in women with type 2 diabetes.

PMID- 11238499
TI  - The melanocortin melanocyte-stimulating hormone/adrenocorticotropin(4-10)
      decreases body fat in humans.
AB  - The control of body fat is a prominent factor in human health. Animal studies
      have indicated a homeostatic central nervous system regulation of body fat with
      particular involvement of the melanocortin receptor pathway. This study provides
      evidence for a similar role for melanocortins in the long-term control of fat
      stores in humans. Thirty-six normal weight humans were assigned to one of three
      experimental groups. After a 4-week baseline, one group was treated with
      MSH/ACTH(4-10) (MSH/ACTH(4-10)) representing the core sequence of all
      melanocortins. Another group received desacetyl-alphaMSH, a selective agonist of
      the brain melanocortin-4 receptor, which shares the 4-10 sequence with MSH/ACTH(4
      10). The third group received placebo. Treatments were given intranasally twice
      daily for 6 weeks, at equimolar doses (MSH/ACTH(4-10), 0.5 mg; desacetyl
      alphaMSH, 0.84 mg). Body weight, body composition, and plasma hormone
      concentrations were measured before and after treatment. MSH/ACTH(4-10) reduced
      body fat, on the average, by 1.68 kg (P < 0.05) and body weight by 0.79 kg (P <
      0.001). Concurrently, plasma leptin levels were decreased by 24% (P < 0.02), and
      insulin levels were decreased by 20% (P< 0.05) after MSH/ACTH(4-10). Changes
      after desacetyl-alphaMSH remained nonsignificant. The finding of reduced body
      adiposity after MSH/ACTH(4-10) confirms and extends to the human the findings of
      animal models indicating an essential role of the hypothalamic melanocortin
      system in body weight control.

PMID- 11238500
TI  - Elevated plasma cortisol in glucose-intolerant men: differences in responses to
      glucose and habituation to venepuncture.
AB  - Recent evidence suggests that variations in cortisol activity within the
      physiological range contribute to associations between multiple cardiovascular
      risk factors. Plasma cortisol measurements during a glucose tolerance test differ
      in men with hypertension, insulin resistance, and glucose intolerance, but it is
      unclear whether this reflects altered responses of cortisol to glucose, altered
      circadian rhythm, or altered habituation to multiple sampling. We performed a
      single-blind randomized cross-over study comparing 75 g oral glucose with placebo
      in 39 fasted men (22 glucose intolerant and 17 controls) aged 68-77 yr. In all
      subjects, plasma cortisol fell during the glucose tolerance test. Subjects with
      glucose intolerance had significantly higher plasma cortisol following placebo (P
      = 0.001), suggesting an altered circadian rhythm. Treatment with an oral glucose
      load blunted the circadian fall in plasma cortisol (P = 0.002), but this response
      was no different in controls or glucose intolerant subjects. In addition, 0900 h
      plasma cortisol was higher in the first study phase in controls (P = 0.01) but
      not in glucose-intolerant subjects (P = 0.18), who showed a lack of habituation
      to repeated plasma measurements. These data support the hypothesis that
      alterations in central regulation of the hypothalamic-pituitary-adrenal axis may
      be important in glucose intolerance.

PMID- 11238501
TI  - Circulating interleukin 6 levels, blood pressure, and insulin sensitivity in
      apparently healthy men and women.
AB  - There is increasing evidence that systemic inflammation and insulin resistance
      constitute interrelated events that contribute to atherosclerosis. We studied the
      effect of the association between circulating interleukin 6 (IL-6) levels, one of
      the major mediators of inflammation, and C-reactive protein on insulin resistance
      and blood pressure in 228 healthy volunteers. The plasma IL-6 concentration was
      significantly and similarly associated with systolic (SBP) and diastolic (DBP)
      blood pressure, fasting insulin, and the fasting insulin resistance index (FIRI)
      in all subjects. When smokers were excluded from the analysis, plasma IL-6 levels
      correlated with percent fat mass (r = 0.19; P = 0.02), absolute fat mass (r =
      0.17; P = 0.03), SBP, DBP, fasting insulin levels, and FIRI. The latter
      associations persisted after controlling for body mass index (r = 0.15 and r =
      0.19; P = 0.02 and P: = 0.0004 for SBP and DBP, respectively; r = 0.24 and r =
      0.19, P = 0.004 and P = 0.03, for fasting insulin and FIRI, respectively). Gender
      and smoking status significantly influenced the results. Although IL-6 levels
      were significantly associated with fasting insulin and FIRI in men, these
      significant correlations were not observed in women. Conversely, although IL-6
      levels were significantly associated with SBP and DBP in women, these
      coefficients were not statistically significant in men. All of these associations
      were lost among smokers and remained significant in nonsmokers. As IL-6 is the
      major mediator of the acute phase response by hepatocytes and induces the
      synthesis of C-reactive protein (CRP), we also controlled for the latter. Serum
      CRP levels correlated significantly with IL-6 in all the subjects, but mainly in
      nonsmokers and men. Of note was that this significant relationship was lost among
      smokers. CRP was associated with fasting insulin (r = 0.28; P < 0.0001) and FIRI
      (r = 0.25; P < 0.0001), but not with SBP or DBP (P = NS), in all subjects. Unlike
      IL-6, the associations between CRP and these parameters were similar in men and
      women and in smokers and nonsmokers. For insulin and FIRI they were stronger in
      women and in nonsmokers. CPR significantly correlated with the WHR only in men (r
      = 0.22; P = 0.01). Using multiple linear regression in a stepwise manner to
      predict circulating IL-6 levels, smoking status (P = 0.0059) and FIRI (P = 0.03),
      but not fat mass or SBP, independently contributed to 11% of its variance in men.
      When CRP was introduced into the model, the latter (P < 0.0001) and smoking
      status (P = 0.02), but not FIRI, fat mass, or SBP, contributed to 33% of the
      variance in IL-6 levels. In women, only SBP (P = 0.04) contributed to 5% of its
      variance. When CRP was introduced into the model, again only SBP (P = 0.01)
      contributed to 10% of the variance in IL-6 levels. In 25 of these subjects,
      insulin sensitivity was determined using the frequently sampled iv glucose
      tolerance test with minimal model analysis, and circulating IL-6 levels were
      strongly associated with the insulin sensitivity index (r = -0.65; P < 0.0001).
      Again, this relationship was even stronger in men (r = -0.75; P < 0.001) and was
      not significant in women (r = -0.26; P = NS). In all of these subjects, only
      insulin sensitivity (P = 0.0037), not fat mass, contributed to 21% of the
      variance of IL-6 levels in a multiple linear regression analysis. In summary,
      circulating IL-6 levels, by inducing either hypertension in women or insulin
      resistance in men, constitute a significant proatherogenic cytokine. The
      mechanisms of these associations should be further investigated.

PMID- 11238502
TI  - Selenium decreases thyroglobulin concentrations but does not affect the increased
      thyroxine-to-triiodothyronine ratio in children with congenital hypothyroidism.
AB  - Compared with euthyroid controls, patients with congenital hypothyroidism (CH)
      who are receiving L-T(4) treatment show elevated serum TSH relative to serum T(4)
      concentrations and increased T(4)/T(3) ratio. These abnormalities could be the
      consequence of impaired activity of the selenoenzymes deiodinases on which
      patients with CH rely to convert the ingested L-T(4) into active T(3). Eighteen
      patients (0.5-15.4 yr), diagnosed with CH in infancy, received selenomethionine
      (SeM, 20-60 microg selenium/day) for 3 months. The study took place in Belgium, a
      country where selenium intake is borderline. Compared with the values observed in
      age- and sex-matched euthyroid controls, patients with CH had decreased selenium,
      thyroglobulin and T(3) concentrations and increased TSH, reverse T(3), and T(4)
      concentrations and T(4)/T(3) ratio at baseline. Selenium supplementation caused a
      74% increase in plasma selenium values but did not affect the activity of the
      selenoenzyme glutathione peroxidase used as a marker of selenium status. SeM
      abolished the TSH difference observed between CH patients and euthyroid controls
      at baseline and caused a significant decrease in thyroglobulin values. Thyroid
      hormone concentrations were not affected by SeM. In conclusion, our data suggest
      that selenium is not a limiting factor for peripheral T(4)-to-T(3) conversion in
      CH patients. In contrast, we find indirect evidence that SeM improves thyroid
      hormones feedback at the hypothalamo-pituitary level and decreases stimulation of
      the residual thyroid tissue, possibly suggesting greater intracellular T(4)-to
      T(3) conversion.

PMID- 11238503
TI  - Maternal isodisomy for chromosome 2p causing severe congenital hypothyroidism.
AB  - Severe congenital hypothyroidism (CH) due to a total iodide organification defect
      (TIOD) is usually due to mutations in the thyroid peroxidase (TPO) gene located
      at chromosome 2p25. A homozygous deletion [DeltaT2512 (codon 808)] in exon 14 was
      identified in a patient with classical TIOD. The transmission pattern of the TPO
      gene in this family was anomalous; the mother was heterozygous for the deletion;
      and the mutation was absent in the father. Polymorphic short tandem repeat (STR)
      markers confirmed paternity and demonstrated on chromosome 2 that the propositus
      was homozygous for most markers on chromosome 2p and that these were identical to
      one of the maternal 2p homologs. A normal karyotype was found in the propositus,
      his parents and sister. We conclude that the homozygosity in the patient is due
      to partial maternal isodisomy of the short arm of chromosome 2, carrying a
      defective TPO gene. The patient, born small for gestational age, develops and
      grows well and appears healthy (while being treated with thyroxine) and has a
      normal phenotype except for a unilateral preauricular skin tag. This shows that
      partial maternal isodisomy for chromosome 2p (2pter - 2p12) is compatible with a
      minimal influence on normal development.

PMID- 11238504
TI  - Endocrine activities of ghrelin, a natural growth hormone secretagogue (GHS), in
      humans: comparison and interactions with hexarelin, a nonnatural peptidyl GHS,
      and GH-releasing hormone.
AB  - An endogenous ligand for the GH secretagogue-receptor (GHS-receptor) has recently
      been isolated, from both the rat and the human stomach, and named ghrelin. It is
      a 28-amino-acid peptide showing a unique structure with an n-octanoyl ester at
      its third serine residue, which is essential for its potent stimulatory activity
      on somatotroph secretion. In fact, it has been demonstrated that ghrelin
      specifically stimulates GH secretion from both rat pituitary cells in culture and
      rats in vivo. The aim of the present study was to test the GH-releasing activity
      of ghrelin in humans and to compare it with that of GHRH and hexarelin (HEX), a
      nonnatural peptidyl GHS, which possesses strong GH-releasing activity but also
      significantly stimulates PRL, ACTH, and cortisol secretion. To clarify the
      mechanisms of action underlying the GH-releasing activity of ghrelin in humans,
      its interaction with GHRH and HEX was also studied. Seven normal young volunteers
      (7 men; 24-32 yr old; body mass index, 20-24 kg/m(2)) were studied. All subjects
      underwent the administration of ghrelin, HEX, and GHRH-29 (1.0 microg/kg i.v. at
      0 min) as well as placebo (2 mL isotonic saline i.v. at 0 min). Six subjects also
      underwent the combined administration of ghrelin and GHRH or HEX. Blood samples
      were taken every 15 min from -15 up to +180 min. GH levels were assayed at each
      time point in all sessions; PRL, ACTH, cortisol, and aldosterone levels were also
      assayed after administration of ghrelin and/or HEX. Ghrelin administration
      induced a prompt and marked increase in circulating GH levels (Cmax, mean +/-
      SEM, 92.1 +/- 16.7 microg/L; area under the curve, 1894.9 +/- 347.8 microg/L.h).
      The GH response to ghrelin was clearly higher (P < 0.01) than the one recorded
      after GHRH (26.7 +/- 8.7 microg/L; 619.6 +/- 174.4 microg/L.h) and even
      significantly higher (P < 0.05) than after HEX (68.4 +/- 14.7 microg/L; 1546.9 +/
      380.0 microg/L x h). Ghrelin administration also induced an increase in PRL,
      ACTH, and cortisol levels; these responses were higher (P < 0.05) than those
      elicited by HEX. A significant increase in aldosterone levels was recorded after
      ghrelin but not after HEX. The endocrine responses to ghrelin were not modified
      by the coadministration of HEX. On the other hand, the coadministration of
      ghrelin and GHRH had a real synergistical effect (P < 0.05) on GH secretion
      (133.6 +/- 22.5 microg/L; 3374.3 +/- 617.3 microg/L x h). In conclusion, ghrelin,
      a natural ligand of GHS-receptor, exerts a strong stimulatory effect on GH
      secretion in humans, releasing more GH than GHRH and even more than a nonnatural
      GHS such as HEX. Ghrelin, as well as HEX, also stimulates lactotroph and
      corticotroph secretion. Ghrelin shows no interaction with HEX, whereas it has a
      synergistical effect with GHRH on GH secretion. Thus, ghrelin is a new hormone
      playing a major role in the control of somatotroph secretion in humans, and its
      effects are imitated by nonnatural GHS.

PMID- 11238505
TI  - Increased prevalence of obstructive sleep apnea syndrome in obese women with
      polycystic ovary syndrome.
AB  - Obstructive Sleep Apnea (OSA) is considerably more common in men than women.
      Preliminary data suggest that androgens may play a role in the male predominance
      of apnea. Polycystic Ovary Syndrome (PCOS) is characterized by menstrual
      disturbances, androgen excess, and frequently obesity. These features suggest
      that women with PCOS may be at increased risk for OSA. To determine whether obese
      women with PCOS have an increased prevalence of sleep apnea compared with age and
      weight-matched reproductively normal women, we performed overnight
      polysomnography for determination of the apnea-hypopnea index (AHI) in 18 obese
      women with PCOS and age and weight-matched control women. Additional measurements
      included waist, hip, and neck circumferences, serum total testosterone, unbound
      testosterone, and DHEAS. Women with PCOS had a higher AHI than controls (22.5 +/-
      6.0, vs. 6.7 +/- 1.0, P = 0.008). Women with PCOS were also more likely to suffer
      from symptomatic OSA syndrome (44.4% vs. 5.5%, P = 0.008). AHI correlated with
      waist-hip ratio (r = 0.51, P < 0.03), serum testosterone (r = 0.52, P < 0.03) and
      unbound testosterone (r = 0.50, P < 0.05) in women with PCOS. We conclude that
      obese women with PCOS are at increased risk of OSA when compared with matched
      reproductively normal women. Women with PCOS should be carefully questioned
      regarding symptoms of sleep apnea.

PMID- 11238506
TI  - Characterization of nocturnal ultradian rhythms of melatonin in children with
      growth hormone-dependent and independent growth delay.
AB  - To assess the existence of a possible nocturnal ultradian rhythm of melatonin in
      children, we analyzed 28 pediatric patients (mean age, 9.08 +/- 2.2 yr) with GH
      dependent and GH-independent growth delay. Plasma melatonin was measured by RIA
      in children sampled every 30 min between 2100-0900 h. Statistical analysis
      consisted of cluster analysis to examine the presence of peaks and troughs. The
      pattern of melatonin levels was related to the cause of growth delay, although
      the means of the nocturnal concentrations of melatonin were similar in all
      children. Interestingly, children with a GH deficit showed a nearly normal
      melatonin profile, whereas children with normal GH values but abnormal growth
      displayed atypical profiles of melatonin. The results also prove the existence of
      an ultradian rhythm of melatonin in most of the patients studied. The ultradian
      rhythm of melatonin in children was characterized by irregular interburst
      intervals, thus differing from the rhythm previously described in adults that had
      an almost constant pulse frequency. Moreover, the existence of low and high
      melatonin producers was revealed in the study, a feature unrelated to the cause
      of growth delay. The group of children with a GH deficit showed the lowest values
      of integrated melatonin production and of the area of peaks and troughs. These
      results prove that children exhibit an ultradian rhythm of melatonin like that in
      adults. Whereas it is not clear whether the episodic production of melatonin is
      required for its biological actions, the existence of irregular pulses may
      reflect endocrine influences at this age and/or the immaturity of the intrinsic
      pulse generator.

PMID- 11238507
TI  - Elevated leptin levels are associated with excess gains in fat mass in girls, but
      not boys, with type 1 diabetes: longitudinal study during adolescence.
AB  - Adolescents, in particular girls, with type 1 diabetes may gain excessive weight
      during puberty. We present the results of a longitudinal study aimed to determine
      the roles of leptin and insulin in changes in body composition in subjects with
      type 1 diabetes and controls. Forty-six children (23 boys) with type 1 diabetes
      and 40 controls (20 boys) were followed from 8-17 yr of age. Height, weight, and
      sc skinfolds were assessed every 6 months, and a blood sample taken for leptin
      determination. Throughout the age range, body mass index (mean +/- SEM) was
      greater by 1.45 +/- 0.69 kg/m(2) in girls and 1.46 +/- 0.55 kg/m(2) in boys with
      type 1 diabetes compared with control values. In girls with type 1 diabetes, this
      reflected greater percent body fat (3.2 +/- 1.0%; P = 0.002), whereas in boys it
      related to differences in fat-free mass. Both boys and girls with type 1 diabetes
      had higher leptin levels adjusted for percent body fat than controls; in the
      girls this was related to insulin dose (regression coefficient B = 0.006 +/-
      0.003; P = 0.04) and greater gains in fat mass. Hyperinsulinemia and raised
      leptin levels are associated with gains in fat mass throughout puberty in girls,
      but not boys, with type 1 diabetes.

PMID- 11238508
TI  - Analysis of the contribution of dydrogesterone to bone turnover changes in
      postmenopausal women commencing hormone replacement therapy.
AB  - Although gestagens have been reported to influence bone metabolism, whether these
      contribute to the beneficial effects of hormone replacement therapy (HRT) on the
      skeleton of postmenopausal women is currently unclear. To address this question,
      we compared changes in bone turnover markers after commencing HRT in 26
      postmenopausal women randomized to receive 8 weeks of treatment with 2 mg
      estradiol daily or 2 mg estradiol plus 10 mg dydrogesterone daily. Serum and
      second morning void urine samples were obtained at baseline (twice) and after 1,
      2, 4, and 8 weeks. Serum estradiol was measured by RIA, urinary total
      deoxypyridinoline (DPD) excretion by high pressure liquid chromatography, and
      serum osteocalcin and C-terminal procollagen peptide by enzyme-linked
      immunosorbent assay. The increase in serum estradiol after treatment with
      estradiol alone was slightly, but significantly, greater than that in the
      combination group (P = 0.04). Although estradiol suppressed urinary DPD excretion
      to a greater extent when given alone (P = 0.02), osteocalcin levels were
      significantly higher in this group than in women receiving combination therapy (P
      = 0.04). To assess the effect of dydrogesterone on the balance between formation
      and resorption in more detail, we subsequently compared the ratio between
      formation and resorption markers in the two treatment groups. We found that
      osteocalcin/DPD and C-terminal procollagen peptide/DPD ratios were significantly
      higher in women treated with estradiol alone (P < 0.0001 and P = 0.002,
      respectively), suggesting that dydrogesterone may reduce formation relative to
      resorption. These results suggest that gestagens may reduce estrogen's beneficial
      effects on the skeleton of postmenopausal women, as assessed over the first 8
      weeks of replacement therapy.

PMID- 11238509
TI  - Genome-wide scan of obesity in the Old Order Amish.
AB  - To identify the genetic determinants of typical obesity, we performed a genome
      wide scan of obesity-related traits using data from the Amish. Multipoint linkage
      analysis was performed using a variance components procedure on body mass index
      (BMI), waist circumference, percentage of body fat, and serum leptin
      concentrations. All 672 individuals were genotyped for 357 markers in 22
      autosomes. We observed modest evidence for linkage, with the maximum log odds
      (lod) scores for linkage for these traits occurring on chromosomes 3p (percentage
      of body fat: lod = 1.61, near the peroxisome proliferator-activated receptor
      alpha gene), 14q (waist: lod = 1.80), and 16p (leptin: lod = 1.72; BMI: lod =
      1.68). We also tested for linkage to BMI-adjusted leptin concentrations and
      observed suggestive evidence for linkage on chromosome 10p (lod = 2.73),
      approximately 10-20 cM telomeric from obesity loci previously reported in French
      and German Caucasians. Two additional linkage signals for this trait were
      observed on chromosomes 7q (lod = 1.77, approximately 20 cM from the leptin gene)
      and 14q (lod = 2.47). Follow-up studies may be warranted to pursue some of these
      linkage signals, especially those detected near known obesity candidate genes,
      and those in regions coinciding with linkage signals reported previously.

PMID- 11238510
TI  - The relationship between thyrotropin and low density lipoprotein cholesterol is
      modified by insulin sensitivity in healthy euthyroid subjects.
AB  - High levels of TSH are associated with an increased cardiovascular risk. Many
      cardiovascular risk factors cluster within the insulin resistance syndrome. It is
      not known whether levels of TSH cluster as well. We conducted this research to
      test the hypothesis that TSH, insulin sensitivity, and levels of low density
      lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C)
      are interdependent in euthyroid subjects. Levels of TSH, free thyroid hormone,
      and serum lipids were measured in fasting serum samples taken before performance
      of a hyperinsulinemic euglycemic clamp to assess insulin sensitivity in 46
      healthy euthyroid subjects with a mean TSH of 1.8 +/- 0.7 mU/L. Significant age-
      and sex-adjusted partial correlations of TSH with LDL-C (r = 0.48; P < 0.01) and
      HDL-C (r = -0.36; P < 0.05) were observed. TSH was not significantly correlated
      with insulin sensitivity or fasting triglyceride concentrations. In line with
      these results, we found the associations of TSH with LDL-C and HDL-C to be
      independent of insulin sensitivity. However, we observed significant effect
      modification of the association of TSH with LDL-C by insulin sensitivity (P =
      0.02). This effect-modification implies a range of associations of TSH with LDL-C
      that varies from absent in insulin-sensitive subjects to strongly positive in
      insulin-resistant subjects. We conclude that the increased cardiovascular risk
      associated with subclinical hypothyroidism seems to extend itself into the normal
      range of thyroid function. Importantly, the effect-modification of the
      association of TSH with LDL-C by insulin sensitivity suggests that insulin
      resistant subjects are most susceptible to this increased risk.

PMID- 11238511
TI  - A global study of vitamin D status and parathyroid function in postmenopausal
      women with osteoporosis: baseline data from the multiple outcomes of raloxifene
      evaluation clinical trial.
AB  - Vitamin D deficiency leads to secondary hyperparathyroidism, increased bone
      turnover, and bone loss and, when severe, to osteomalacia. Vitamin D deficiency
      is common in elderly people, especially the institutionalized. The definition of
      vitamin D deficiency is hampered by the fact that large interlaboratory
      differences exist in assays for serum 25-hydroxyvitamin D (25OHD), the main
      circulating metabolite. The international Multiple Outcomes of Raloxifene
      Evaluation study, a large prospective intervention trial in postmenopausal women
      with osteoporosis, offered the opportunity to compare vitamin D status and
      parathyroid function throughout many countries over the world. For this study,
      baseline data were available from 7564 postmenopausal women from 25 countries on
      5 continents. All women had osteoporosis, i.e. bone mineral density (BMD) at
      femoral neck or lumbar spine was lower than t-score -2.5, or they had 2 vertebral
      fractures. Serum 25OHD was measured by RIA, and serum PTH was measured by
      immunoradiometric assay. BMD was measured by dual x-ray absorptiometry. The mean
      (+/-SD) serum 25OHD was 70.8 +/- 30.9 nmol/L. A low serum 25OHD (<25 nmol/L) was
      observed in 4.1% of all women in the Multiple Outcomes of Raloxifene Evaluation
      study, ranging from 0% in south east Asia (very few patients) to 8.3% in southern
      Europe. Serum 25OHD was between 25-50 nmol/L in 24.3% of the women. Serum 25OHD
      showed a significant seasonal relationship, with lower values in all regions in
      winter. Serum PTH correlated negatively with serum 25OHD (r = -0.25; P < 0.001).
      This significant negative correlation was observed in all regions. When serum
      25OHD was less than 25, 25-50, or more than 50 nmol/L, respectively, mean serum
      PTH levels were 4.8, 4.1, and 3.5 pmol/L, respectively (by ANOVA, P < 0.001).
      Similarly, mean alkaline phosphatase levels were 83.7, 79.1, and 75.7 U/L (P <
      0.001), respectively, with increasing serum 25OHD. The effect of serum 25OHD on
      BMD was only significant for the BMD of the trochanter where a serum 25OHD level
      less than 25 nmol/L was associated with a 4% lower BMD. After 6 months of
      treatment with vitamin D(3) (400-600 IU/day) and calcium (500 mg/day), serum
      25OHD increased from 70.8 +/- 29.8 to 92.3 +/- 28.6 nmol/L. Serum PTH decreased
      significantly after 6 months of treatment, and this decrease depended on baseline
      serum 25OHD. When baseline serum 25OHD was less than 25, 25-50, or more than 50
      nmol/L, respectively, serum PTH decreased by 0.8, 0.5, or 0.2 pmol/L,
      respectively (P < 0.001). In conclusion, serum 25OHD was less than 25 nmol/L in
      4% of the women, and this was associated with a 30% higher serum PTH. In 24% of
      the women serum 25OHD was between 25-50 nmol/L, associated with a 15% higher
      level of serum PTH compared with women with a serum 25OHD greater than 50 nmol/L.
      A low serum 25OHD level was also associated with higher serum alkaline
      phosphatase and lower BMD of the trochanter. Treatment with vitamin D(3) and
      calcium increased serum 25OHD and decreased serum PTH significantly; the effect
      was greater for lower baseline serum 25OHD.

PMID- 11238512
TI  - Long-term effects of continuous subcutaneous infusion versus daily subcutaneous
      injections of growth hormone (GH) on the insulin-like growth factor system,
      insulin sensitivity, body composition, and bone and lipoprotein metabolism in GH
      deficient adults.
AB  - It remains uncertain whether close imitation of the physiological pulsatile GH
      pattern determines the effects of GH treatment in humans. However, human studies
      have reported comparable metabolic responses to short-term constant and
      intermittent GH exposure. The aim of the study was to compare the metabolic
      effects of GH after continuous and intermittent sc delivery. In a parallel
      design, 14 GH-treated GH-deficient patients (mean age, 37 yr; mean body mass
      index, 27.4 kg/m(2)) were studied during steady state at the start of the study
      and after 6 months. Seven patients received daily injections (inj) in the evening
      as usual, and 7 received a continuous infusion (inf) of GH by means of a portable
      pump. The GH dose was kept unchanged before and during the study. Serum levels of
      insulin-like growth factor I (IGF-I) tended to increase in the patients switched
      to constant infusion (from 175 +/- 36 to 209 +/- 50 microg/L), but the
      differences obtained during the two regimens [+34.3 (inf) vs. -11.9 (inj)] were
      not significant (P = 0.34). Serum levels of IGF-II (P = 0.71) and IGF-binding
      protein (IGFBP)-3 (P = 0.75) were identical during the two modes of treatment.
      Serum levels of IGFBP-1 (P = 0.72), IGFBP-2 (P = 0.34), and GH-binding protein (P
      = 0.75) were unaffected by treatment regimen. Serum levels of free fatty acids,
      reflecting lipolysis, decreased significantly (16%) in the group switched to GH
      infusion (difference, -99.8 vs. +5 micromol/L; P < 0.03). The GH pattern did not
      influence insulin sensitivity (P = 0.71) or glucose effectiveness (P = 0.15)
      derived from Bergman's minimal model. Similarly, the two treatment regimens had
      no differential impact on lipoprotein levels, bone metabolism, or body
      composition. In conclusion, continuous and intermittent administrations of GH for
      6 months are comparable with respect to the IGF-IGFBP axis, whereas intermittent
      exposure may be of importance for the lipolytic effect of GH. The data on insulin
      sensitivity and lipoproteins suggest that constant GH exposure is as safe as
      intermittent GH administration.

PMID- 11238513
TI  - Action of glucagon and glucagon-like peptide-1-(7-36) amide on lipolysis in human
      subcutaneous adipose tissue and skeletal muscle in vivo.
AB  - In vitro and animal studies have shown that glucagon and glucagon-like peptide-1
      (GLP-1)-(7-36) amide may participate in the regulation of lipolysis. However,
      results on human subjects in vivo are inconclusive. To avoid confounding effects,
      such as changes in insulin secretion when perfusing hormones iv, we used the in
      situ microdialysis to analyze the impact of human glucagon and GLP-1 on lipolysis
      rates and local blood flow. Nine healthy volunteers were given an 80-min local
      perfusion of each hormone (10(-6) mol/L), both in skeletal muscle (gastrocnemius)
      and in sc abdominal adipose tissue, after a basal period with perfusion of
      Ringer's solution. Variations in the lipolysis rate and blood flow, respectively,
      were assessed by measuring of the dialysate glycerol content and the ethanol
      ratio (outgoing-to-ingoing ethanol concentration). The in vitro relative recovery
      of the microdialysis probes was 5.2 +/- 1.2%. No significant effects of either
      GLP-1 or glucagon on either lipolysis rate or blood flow were detected in muscle
      or adipose tissue. Isoprenaline (10(-6) mol/L), which was perfused after glucagon
      or GLP-1 in the same catheters, significantly increased the lipolysis rate (a
      249% increase of dialysate glycerol in adipose tissue and a 72% increase in
      skeletal muscle). Furthermore, isoprenaline, but not glucagon or GLP-1,
      stimulated lipolysis in vitro in isolated human sc adipose tissue. We conclude
      that neither glucagon nor GLP-1 affect the lipolysis rate of human sc adipose
      tissue or skeletal muscle.

PMID- 11238514
TI  - Evidence against a rate-limiting role of proinsulin processing for maximal
      insulin secretion in subjects with impaired glucose tolerance and beta-cell
      dysfunction.
AB  - In subjects with impaired glucose tolerance (IGT) insulin secretion is impaired.
      Increased proinsulin/insulin (PI/I) ratios suggest that there is also reduced
      processing of proinsulin to insulin in this condition. The PI/I ratio in the
      insulin secretory granule is ideally assessed by plasma measurements in response
      to acute stimulation of insulin secretion. In the present study we tested the
      hypothesis that maximal stimulation of insulin secretion results in exhaustion of
      the proinsulin conversion pathway to insulin. We therefore determined the PI/I
      ratio in 11 normal glucose-tolerant subjects (NGT) and 11 subjects with IGT in
      response to glucose (squarewave hyperglycemic clamp, 10 mmol/L), glucagon-like
      peptide-1 (GLP-1; primed-continuous infusion), and arginine given during the
      continued GLP-1 infusion. In IGT, insulin levels were significantly lower during
      the first phase (144 +/- 20 vs. 397 +/- 119 pmol/L; P = 0.02), at the end of the
      GLP infusion (2142 +/- 350 vs. 5430 +/- 1091 pmol/L; P: = 0.002), and in response
      to arginine (3983 +/- 375 vs. 8663 +/- 1430 pmol/L; P = 0.005). In response to
      glucose, the minimum PI/I ratio was significantly higher in IGT (3.4 +/- 0.6%)
      than in NGT (1.4 +/- 0.5%; P = 0.02), suggesting defective proinsulin processing
      in this condition. In subjects with IGT, the PI/I ratio decreased significantly
      after GLP-1 priming (1.7 +/- 0.2%; P = 0.02) and after arginine given during GLP
      1 (1.4 +/- 0.2%; P = 0.007) and was not significantly different from those values
      in NGT (1.3 +/- 0.2% and 1.3 +/- 0.2%, respectively; both P = NS). In conclusion,
      during maximal stimulation of insulin secretion in subjects with IGT, the PI/I
      ratio in plasma decreased significantly and was not different from that in normal
      controls. This strongly argues against the hypothesis that defective processing
      of proinsulin to insulin represents a major component of the beta-cell
      dysfunction in IGT.

PMID- 11238515
TI  - Phenotypic variation in a family with partial androgen insensitivity syndrome
      explained by differences in 5alpha dihydrotestosterone availability.
AB  - Mutations in the androgen receptor (AR) gene result in a wide range of phenotypes
      of the androgen insensitivity syndrome (AIS). Inter- and intrafamilial
      differences in the phenotypic expression of identical AR mutations are known,
      suggesting modifying factors in establishing the phenotype. Two 46,XY siblings
      with partial AIS sharing the same AR gene mutation, R846H, but showing very
      different phenotypes are studied. Their parents are first cousins. One sibling
      with grade 5 AIS was raised as a girl; the other sibling with grade 3 AIS was
      raised as a boy. In both siblings serum levels of hormones were measured; a sex
      hormone-binding globulin (SHBG) suppression test was completed; and mutation
      analysis of the AR gene, Scatchard, and SDS-PAGE analysis of the AR protein was
      performed. Furthermore, 5alpha-reductase 2 expression and activity in genital
      skin fibroblasts were investigated, and the 5alpha-reductase 2 gene was
      sequenced. The decrease in SHBG serum levels in a SHBG suppression test did not
      suggest differences in androgen sensitivity as the cause of the phenotypic
      variation. Also, androgen binding characteristics of the AR, AR expression
      levels, and the phosphorylation pattern of the AR on hormone binding were
      identical in both siblings. However, 5alpha-reductase 2 activity was normal in
      genital skin fibroblasts from the phenotypic male patient but undetectable in
      genital skin fibroblasts from the phenotypic female patient. The lack of 5alpha
      reductase 2 activity was due to absent or reduced expression of 5alpha-reductase
      2 in genital skin fibroblasts from the phenotypic female patient. Exon and
      flanking intron sequences of the 5alpha-reductase 2 gene showed no mutations in
      either sibling. Additional intragenic polymorphic marker analysis gave no
      evidence for different inherited alleles for the 5alpha-reductase 2 gene in the
      two siblings. Therefore, the absent or reduced expression of 5alpha-reductase 2
      is likely to be additional to the AIS. Distinct phenotypic variation in this
      family was caused by 5alpha-reductase 2 deficiency, additional to AIS. This
      5alpha-reductase deficiency is due to absence of expression of the 5alpha
      reductase iso-enzyme 2 as shown by molecular studies. The distinct phenotypic
      variation in AIS here is explained by differences in the availability of 5alpha
      dihydrotestosterone during embryonic sex differentiation.

PMID- 11238516
TI  - A mutation in the cofactor-binding domain of 11beta-hydroxysteroid dehydrogenase
      type 2 associated with mineralocorticoid hypertension.
AB  - Renal 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) is an enzyme
      responsible for the peripheral inactivation of cortisol to cortisone in
      mineralocorticoid target tissues. Mutations in the gene encoding 11betaHSD2 cause
      the syndrome of apparent mineralocorticoid excess (AME), an autosomal recessive
      form of inherited hypertension, in which cortisol acts as a potent
      mineralocorticoid. The mutations reported to date have been confined to exons 3
      5. Here, we describe two siblings, 1 and 2 yr old, who were diagnosed with
      hypokalemic hypertension and low plasma aldosterone and renin levels, indicating
      mineralocorticoid hypertension. Analysis of urinary steroid metabolites showed a
      markedly impaired metabolism of cortisol, with (tetrahydrocortisol + 5alpha
      tetrahydrocortisol)/tetrahydrocortisone ratios of 40-60, and nearly absent
      urinary free cortisone. Although phenotypically normal, the heterozygous parents
      showed a disturbed cortisol metabolism. Genetic analysis of the HSD11B2 gene from
      the AME patients revealed the homozygous deletion of six nucleotides in exon 2
      with the resultant loss of amino acids Leu(114) and Glu(115), representing the
      first alteration found in the cofactor-binding domain. The deletion mutant,
      expressed in HEK-293 cells, showed an approximately 20-fold lower maximum
      velocity but increased apparent affinity for cortisol and corticosterone. In
      contrast, two additionally constructed substitutions, Glu(115) to Gln or Lys,
      showed increased maximal velocity and apparent affinity for 11beta
      hydroxyglucocorticoids. Functional analysis of wild-type and mutant proteins
      indicated that a disturbed conformation of the cofactor-binding domain, but not
      the missing negative charge of Glu(115), led to the observed decreased activity
      of the deletion mutant. Considered together, these findings provide evidence for
      a role of Glu(115) in determining cofactor-binding specificity of 11betaHSD2 and
      emphasize the importance of structure-function analysis to elucidate the
      molecular mechanism of AME.

PMID- 11238517
TI  - Activation of the parasympathetic nervous system is necessary for normal meal
      induced insulin secretion in rhesus macaques.
AB  - Meal-induced insulin secretion is thought to be regulated primarily by absorbed
      nutrients and incretin hormones released from the gastrointestinal tract. In
      addition, the parasympathetic nervous system (PNS) is known to mediate
      preabsorptive, or cephalic phase, insulin secretion. Despite evidence that the
      PNS remains activated during the absorptive phase of the meal, its role in
      mediating postprandial insulin secretion has not been established. To study the
      role of the PNS in absorptive phase insulin release, we measured plasma
      concentrations of glucose as well as islet hormones and incretins in six healthy
      rhesus monkeys before and for 60 min after meals while they were infused with
      saline (control), atropine (muscarinic blockade), or trimethaphan (nicotinic
      blockade). During the infusion of saline, plasma levels of glucose, pancreatic
      polypeptide (PP), insulin, glucose-dependent insulinotropic polypeptide, and
      glucagon-like peptide-1 increased promptly after meal ingestion and remained
      elevated throughout the 60 min of the study. The PP response was nearly abolished
      in animals treated with trimethaphan, indicating functional blockade of PNS input
      to the islet, and in contrast to the control study, there were minimal changes in
      plasma concentrations of glucose, incretin hormones, and insulin. Because
      trimethaphan inhibited glycemic and incretin stimuli in addition to blocking PNS
      input to the islet, it was not possible to discern the relative roles of these
      factors in the stimulation of insulin secretion. Atropine also significantly
      decreased PNS transmission to the islet, as reflected by PP levels similar to
      those observed with trimethaphan. Unlike the trimethaphan study, plasma glucose
      levels rose normally during atropine treatment and were similar to those in the
      control study over the course of the experiments (114 +/- 22 and 132 +/- 23
      mmol/L.60 min, respectively). In addition, the rise in plasma glucagon-like
      peptide-1 following the meal was not suppressed by atropine, and the glucose
      dependent insulinotropic polypeptide responses were only modestly decreased.
      Despite the significant increases in circulating glucose and incretins, plasma
      insulin levels were greatly attenuated by atropine, so that the 60 min responses
      were more comparable to those during trimethaphan treatment than to those in the
      control study (atropine, 3,576 +/- 1,284; trimethaphan, 4,128 +/- 2,616; control,
      15,834 +/- 5,586 pmol/L.60 min; P: < 0.05). Thus, muscarinic blockade markedly
      suppressed the meal-induced insulin response despite normal postprandial glycemia
      and significant elevations of incretins. These results indicate that activation
      of the PNS during the absorptive phase of meals contributes significantly to the
      postprandial insulin secretory response.

PMID- 11238518
TI  - Measurement of intact insulin-like growth factor-binding protein-3 in human
      plasma using a ligand immunofunctional assay.
AB  - Limited proteolysis of insulin-like growth factor binding protein-3 (IGFBP-3) is
      a fundamental mechanism in the regulation of IGF-I bioavailability in the
      bloodstream. Its measurement by Western immunoblotting provides only
      semiquantitative estimation. We have developed a ligand immunofunctional assay
      (LIFA) for quantifying human (h) intact IGFBP-3 in biological fluids. IGFBP-bound
      IGFs are dissociated and separated by acid pH ultrafiltration, and a monoclonal
      antibody specific to the first 160 amino acids of IGFBP-3 is used to capture
      hIGFBP-3 in a solid-phase assay. The complex is then incubated with (125)I-IGF-I,
      which binds to intact IGFBP-3 but not to its proteolytic fragments. Binding
      specificity was demonstrated in competition experiments with unlabeled IGF.
      Nonspecific binding was 1.4%. The fragments comprising residues 1-160 and 1-95 of
      recombinant hIGFBP-3 [corresponding to the major proteolytic fragments of
      approximately 30 kDa and (glycosylated) 20 or (nonglycosylated) 16 kDa detected
      in serum by Western immunoblotting, respectively] fail to bind (125)I-IGF-I when
      complexed with the monoclonal antibody. Similarly, no binding of (125)I-IGF-I was
      obtained in the LIFA when applied to plasmas from pregnant women during the final
      3 months of pregnancy, where the characteristic 42- to 39-kDa doublet of intact
      IGFBP-3 is undetectable. The standard curve was established using a pool of
      plasmas (EDTA) from healthy adults, for which standardization with glycosylated
      recombinant hIGFBP-3 yielded an intact IGFBP-3 content of 2 microg/mL. The
      dynamic range of the LIFA was 0.50-3.75 microL equivalent of the plasma pool in a
      total volume of 300 microL per assay tube, with a sensitivity threshold of
      approximately 1 ng intact IGFBP-3. Unknown plasma samples were studied at three
      concentrations. Intra- and interassay variations were 3.6% and 4%, respectively.
      In 31 healthy adults, the mean plasma concentration of intact IGFBP-3 was 2.24 +/
      0.08 (SEM) mg/L, and that of total IGFBP-3 measured by immunoradiometric assay
      was 3.27 +/- 0.14 mg/L. The calculated mean proportion of proteolysed IGFBP-3 was
      29.4 +/- 1.9%. In these subjects, a close correlation was found between intact
      and total IGFBP-3 (r = 0.71, P = 0.0001). The LIFA for IGFBP-3, therefore,
      provides accurate and sensitive measurement of intact IGFBP-3, the form with the
      functional capacity to sequester IGF-I in the bloodstream by association with the
      acid-labile subunit in 140-kDa complexes. In combination with total IGFBP-3 and
      IGF-I assays, the LIFA opens new perspectives in investigating the regulation of
      IGFBP-3 proteolysis and IGF-I bioavailability in man.

PMID- 11238519
TI  - Regulation of interleukin 8 production and gene expression in human adipose
      tissue in vitro.
AB  - A variety of cytokines and other compounds are produced in the human adipose
      tissue and may have autocrine functions in the adipose tissue as well as be
      involved in the complications seen in association with obesity. Because it
      recently has been reported that interleukin 8 (IL-8), through its effects on the
      macrophage and endothelial cell, may be involved in the pathogenesis of
      atherosclerosis, we found it of interest to investigate whether IL-8 is produced
      in human adipose tissue in vitro. Human sc adipose tissue was investigated both
      in incubations with whole adipose tissue fragments as well as with isolated
      mature adipocytes. In adipose tissue fragments, IL-1beta (3 nM) and tumor
      necrosis factor alpha (0.6 nM) were able to stimulate IL-8 production by 12-fold
      and 5-fold, respectively (P < 0.001), when incubated for 48 h. Incubations with
      isolated adipocytes were performed up to 6 h, and IL-1beta and tumor necrosis
      factor alpha significantly increased IL-8 production by 50-60% (P < 0.05).
      Dexamethasone (50 nM) decreased IL-8 production from adipose tissue fragments by
      57% (P < 0.01) and from adipocytes by 37% (P < 0.05). IL-8 messenger RNA
      expression in adipocytes incubated with IL-1beta was increased already after 2 h
      (P < 0.05). Thus, the effect of proinflammatory cytokines and dexamethasone on IL
      8 production in adipose tissue seems to be mediated at the transcriptional level.
      In conclusion, it is demonstrated for the first time that IL-8 is produced and
      released from human adipose tissue and from isolated adipocytes in vitro, which
      may indicate that IL-8 from adipose tissue could be involved in some of the
      obesity-related complications.

PMID- 11238520
TI  - Novel promoter polymorphism in insulin-like growth factor-binding protein-3:
      correlation with serum levels and interaction with known regulators.
AB  - Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) is a major
      determinant of circulating levels of the IGFs and is clinically useful for the
      evaluation of GH deficiency and for predicting the response to GH treatment.
      Recent studies provide evidence that the circulating level of IGFBP-3 is
      inversely related to the risk of several common cancers, and that
      antiproliferative agents such as antiestrogens and retinoids act in part by up
      regulating IGFBP-3 gene (IGFBP3) expression. Although approximately 50% of the
      substantial interindividual variability in circulating IGFBP-3 levels is known to
      have a genetic basis, the specific loci involved are unknown. Direct sequencing
      of genomic DNA specimens from a multiethnic population identified several single
      nucleotide polymorphisms in the promoter region of IGFBP3. For the most common
      single nucleotide polymorphism (nucleotide -202) found to be in Hardy-Weinberg
      equilibrium, genotype was highly correlated to circulating level of IGFBP-3 in
      478 men from the Physicians' Health Study. In vitro, we documented significantly
      higher promoter activity of the A allele at the -202 locus compared with the C
      allele, consistent with the relationship observed between genotype and
      circulating IGFBP-3 (AA > AC > CC). A positive correlation was observed between
      circulating retinol levels and circulating IGFBP-3 levels; subset analysis by
      genotype showed that this relationship was only present among individuals
      carrying an A allele at -202 (AA > AC > CC). Tall individuals or individuals with
      a body mass index of 27 or greater had levels of circulating IGFBP-3 that were
      significantly higher when they possessed at least one A allele (AA > AC > CC).
      The IGFBP3 promoter region deserves investigation as a locus where polymorphic
      variation occurs frequently and may influence GH responsiveness, somatic growth,
      and possibly cancer risk.

PMID- 11238521
TI  - The role of human chorionic gonadotropin on decidualization of endometrial
      stromal cells in vitro.
AB  - Although decidualization of endometrial stromal cells (ESC) is crucial for
      blastocyst implantation and maintenance of pregnancy, its complex mechanism still
      remains largely unknown. It has long been believed that hCG can directly induce
      in vitro decidualization of ESC via cAMP signaling. Recently, however, it has
      been reported that the LH/CG receptor is not present in human endometrium, and
      the direct effect of hCG on decidualization has become controversial. To
      reevaluate the exact effect of hCG on decidualization, human ESC were isolated
      and cultured with hCG and/or ovarian steroids. ESC treated with 17beta-estradiol
      plus progesterone (E(2)/P) transformed morphologically and produced significant
      PRL, whereas ESC treated with hCG alone showed no significant increase in PRL in
      culture medium and exhibited no morphological changes. Moreover, hCG did not
      promote E(2)/P-induced PRL production or intracellular cAMP accumulation, and
      protein kinase A inhibitor failed to block E(2)/P-induced PRL production. These
      results suggest that hCG does not directly affect in vitro decidualization of
      human ESC and that the process of E(2)/P-induced in vitro decidualization might
      consist of several pathways, including the intracellular cAMP signaling cascade.

PMID- 11238523
TI  - Accumulation of high-density lipoprotein-derived estradiol-17beta fatty acid
      esters in low-density lipoprotein particles.
AB  - Estrogens are known to be powerful antioxidants in lipid-aqueous systems, as
      demonstrated by their inhibition of low-density lipoprotein (LDL) oxidation in
      vitro. Studies reporting that endogenous human estrogens could be rendered fat
      soluble by esterification with fatty acids in vivo, and the subsequent detection
      of such esters in blood and fat tissue suggested a possible mechanism explaining
      how estrogens might protect LDL. Because of their lipophilicity, esterified
      estrogens may become incorporated in the lipoprotein structure, providing
      antioxidant potential for the particles. We incubated labeled 17beta-estradiol
      with ovarian follicular fluid and with plasma in the absence and presence of the
      LCAT inhibitor DTNB. This was followed by ultracentrifugal isolation of LDL and
      high-density lipoprotein and analysis of the radioactive label in the "ester" and
      "free" fractions purified from these lipoproteins. The results indicated that
      LCAT-mediated synthesis of esterified 17beta-estradiol occurred in high-density
      lipoprotein particles, and suggested a novel cholesterol ester transfer protein
      mediated mechanism for their transfer to LDL particles.

PMID- 11238522
TI  - A prion-like shift between two conformational forms of a recombinant thyrotropin
      receptor A-subunit module: purification and stabilization using chemical
      chaperones of the form reactive with Graves' autoantibodies.
AB  - A secreted recombinant TSH receptor (TSHR) ectodomain variant (TSHR-289)
      neutralizes TSHR autoantibodies in Graves' disease, but is heterogeneous in
      containing both immunologically active and inactive molecules and is also
      unstable. We have now purified each form of TSHR-289 using sequential affinity
      chromatography with a mouse mAb (3BD10) specific for the inactive form, and a mAb
      to C-terminal His residues that recognizes both forms. The immunological
      difference between active and inactive TSHR-289 was unrelated to primary amino
      acid sequence or carbohydrate content and was, therefore, attributable to its
      folded state. The epitopes for Graves' autoantibodies and 3BD10 overlap, and both
      are destroyed by denaturation. Therefore, reciprocal binding by autoantibodies
      and 3BD10 to conformational determinants involving the same TSHR segment suggests
      a prion-like shift between two folded states of the molecule. Despite
      purification, immunologically active TSHR-289 remained labile, as determined by
      loss of autoantibody, and gain of 3BD10, recognition. However, using chemical
      chaperones we have, for the first time, been able to stabilize purified TSHR
      antigen in immunologically intact form. In summary, purification of
      immunologically active and stable antigen in milligram quantities provides a
      powerful tool for future diagnostic and therapeutic studies in Graves' disease.

PMID- 11238524
TI  - Hyperglycemia acutely increases monocyte extracellular signal-regulated kinase
      activity in vivo in humans.
AB  - Glycemic spikes may negatively affect the long-term prognosis of patients with
      diabetes. Extracellular signal-regulated kinases (ERKs) are intracellular
      mediators of cell proliferation, and they can be activated in response to high
      glucose levels. However, the modifications of their activity in response to
      hyperglycemia have been poorly investigated, in vivo, in humans. Thus, we sought
      to determine in circulating monocytes: 1) the role of hyperglycemia in ERKs
      activity and phosphorylation, and 2) whether hyperglycemia affects mitogen
      activated protein kinase kinase (MEK) activity and mitogen-activated protein
      phosphatase-1 (MKP-1) expression. These goals were performed in five normal
      subjects. Baseline monocyte ERKs activity was 60 +/- 5 pmol/min.mg protein; when
      exogenous hyperglycemia was induced, both monocyte ERKs activity (81 +/- 11
      pmol/min.mg protein; P < 0.05) and phosphorylation significantly increased (P <
      0.01). MEK activity was significantly increased by hyperglycemia (1251 +/- 136
      vs. 2000 +/- 42 cpm; P = 0.0017), whereas no changes were observed in MKP-1
      expression. We conclude that hyperglycemia acutely stimulates ERKs activity and
      phosphorylation in human monocytes by the MEK pathway in vivo. These findings may
      be relevant in understanding the negative role of acute hyperglycemia on monocyte
      pathophysiology.

PMID- 11238525
TI  - Suppression of nuclear factor-kappaB and stimulation of inhibitor kappaB by
      troglitazone: evidence for an anti-inflammatory effect and a potential
      antiatherosclerotic effect in the obese.
AB  - To elucidate whether troglitazone exerts an antiinflammatory effect in humans, in
      vivo, we investigated the suppression of nuclear factor kappaB (NFkappaB) in
      mononuclear cells (MNC) by this drug. We measured intranuclear NFkappaB, total
      cellular NFkappaB, inhibitor kappaB (IkappaB)alpha, reactive oxygen species (ROS)
      generation, and p47(phox) subunit (a key component protein of nicotinamide
      adenine dinucleotide phosphate oxidase) in MNC. Plasma tumor necrosis factor
      (TNF)-alpha, soluble intercellular adhesion molecule-1 (sICAM-1), monocyte
      chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor type 1 (PAI
      1), C-reactive protein (CRP), and interleukin (IL)-10 (antiinflammatory cytokine)
      concentrations were also measured as mediators of inflammatory activity that are
      regulated by the proinflammatory transcription factor NFkappaB. Seven nondiabetic
      obese patients were given 400 mg troglitazone daily for 4 weeks. Blood samples
      were collected before and at weekly intervals thereafter. MNC were separated; and
      the levels of intranuclear NFkappaB, total cellular NFkappaB, IkappaBalpha, and
      p47 (phox) subunit and ROS generation were determined. Plasma was used to measure
      insulin glucose, TNFalpha, sICAM, MCP-1, PAI-1, CRP, and IL-10. Plasma insulin
      concentrations fell significantly at week 1, from 31.2 +/- 29.1 to 14.2 +/- 11.4
      mU/L (P < 0.01) and remained low throughout 4 weeks. Plasma glucose
      concentrations did not alter significantly. There was a fall in intranuclear
      NFkappaB, total cellular NFkappaB, and p47 (phox) subunit, with an increase in
      cellular IkappaBalpha at week 2, which persisted until week 4. There was a
      parallel fall in ROS generation by MNC at week 1; this progressed and persisted
      until week 4 (P < 0.001). Plasma TNF-alpha, sICAM-1, MCP-1, and PAI-1
      concentrations fell significantly at week 4. Plasma IL-10 concentration increased
      significantly, whereas plasma CRP concentrations decreased. We conclude that
      troglitazone has an antiinflammatory action that may contribute to its putative
      antiatherosclerotic effects.

PMID- 11238526
TI  - Decreased gene expression of 11beta-hydroxysteroid dehydrogenase type 2 and 15
      hydroxyprostaglandin dehydrogenase in human placenta of patients with
      preeclampsia.
AB  - Cortisol reduces the activity of the PG-inactivating enzyme 15
      hydroxyprostaglandin dehydrogenase (PGDH) in human placental cells. The objective
      was to investigate a possible relation between 11beta-hydroxysteroid
      dehydrogenase type 2 (11beta-HSD2), converting cortisol to cortisone, and PGDH
      gene expression in the placenta of patients with preeclampsia. In placental
      tissue taken from 20 healthy women with normal pregnancy, 20 premature babies
      born after labor before term, and 18 neonates after preeclamptic pregnancy,
      11beta-HSD2 and PGDH messenger RNA (mRNA) expression was determined using
      quantitative TaqMan real-time PCR and quantitative competitive PCR. When
      comparing matched pairs, there were 3-fold lower 11beta-HSD2/glyceraldehyde-3
      phosphate dehydrogenase (11beta-HSD2/GAPDH) mRNA levels in placentas of patients
      with preeclampsia than in controls [0.18 +/- 0.04 relative units (RU) and 0.61 +/
      0.10 RU, P = 0.0003]. We also found a 2-fold reduction in placental PGDH/GAPDH
      mRNA concentrations (0.28 +/- 0.15 RU and 0.50 +/- 0.18 RU, P = 0.0003). PGDH and
      11beta-HSD2 mRNA levels correlated significantly (r = 0.66, P < 0.0001). In term
      placenta, 11beta-HSD2/GAPDH, but not PGDH, showed a significant correlation to
      birth weight (r = 0.43, P = 0.01) and to placental weight (r = 0.47, P = 0.01).
      Results could be confirmed by competitive PCR. We conclude that, in preeclampsia,
      11beta-HSD2 mRNA expression is reduced, leading to the known decrease of 11beta
      HSD2 activity. By means of an autocrine or paracrine mechanism, the diminished
      conversion of placental cortisol may lead to reduced PGDH mRNA expression as
      found in the present study.

PMID- 11238527
TI  - Luteinizing hormone receptor, steroidogenesis acute regulatory protein, and
      steroidogenic enzyme messenger ribonucleic acids are overexpressed in thecal and
      granulosa cells from polycystic ovaries.
AB  - Recent data suggest that steroidogenic enzyme messenger ribonucleic acids (mRNAs)
      may be overexpressed in thecal cells, and LH receptors may be prematurely
      expressed in granulosa cells in women with polycystic ovaries. The purpose of
      this study was to determine whether there is abnormal gene expression in thecal
      and granulosa cells from polycystic ovaries. Ovarian tissue specimens were
      obtained from 12 women with PCOS and 24 regularly cycling control women. The
      granulosa cells and the theca interna were microdissected from individual
      follicles. LH receptor, steroidogenesis acute regulatory protein (StAR),
      cholesterol side-chain cleavage cytochrome P450 (CYP11A), and 17alpha
      hydroxylase/C(17-20) lyase cytochrome P450 (CYP17) mRNAs were measured by RT-PCR.
      There was no difference between 3- to 7-mm control follicles and dominant
      follicles with respect to LH receptor mRNA expression in either thecal or
      granulosa cells. CYP11A and CYP17 mRNAs were higher in thecal cells from 3- to 7
      mm follicles than in dominant follicles, but StAR expression was not different.
      In granulosa cells, StAR and CYP11A mRNA expression was higher in dominant
      follicles than in 3- to 7-mm follicles. The mean levels of LH receptor, StAR,
      CYP11A, and CYP17 mRNA expression were higher in thecal cells from PCOS follicles
      than in size-matched control follicles. In granulosa cells, the mean levels of LH
      receptor and CYP11A, but not StAR, mRNA expression were higher in PCOS than in
      control follicles. These data demonstrate that regulatory protein and
      steroidogenic enzyme mRNAs are overexpressed in thecal and granulosa cells from
      polycystic ovaries and support the conclusions that the thecal cells are
      hyperstimulated and the granulosa cells may be prematurely luteinizing.

PMID- 11238528
TI  - Characterization of the 5alpha-reductase-3alpha-hydroxysteroid dehydrogenase
      complex in the human brain.
AB  - Although androgen metabolism in the human brain was discovered almost 30 yr ago,
      conclusive studies on the enzymes involved are still lacking. We therefore
      investigated 5alpha-reductase and colocalized 3alpha-hydroxysteroid dehydrogenase
      (3alpha-HSD) activity in cerebral neocortex (CX) and subcortical white matter
      (SC) specimens neurosurgically removed from 44 patients suffering from epilepsy.
      We could demonstrate the presence of the 5alpha-reductase-3alpha-HSD complex in
      the biopsies of all patients under investigation. Inhibition experiments with
      specific inhibitors for 5alpha-reductase type 1 and type 2 revealed strong
      evidence for the exclusive activity of the type 1 isoform. We detected a
      significantly higher 5alpha-reductase activity in CX than in SC (P< 0.0001), but
      no sex-specific differences were observed. Furthermore, we found that, in
      contrast to liver, only 3alpha-HSD type 2 messenger RNA is expressed in the brain
      and that its expression is significantly higher in SC than in CX without sex
      specific differences. The present study is the first to systematically
      characterize the 5alpha-reductase-3alpha-HSD complex in the human brain. The lack
      of sex-specific differences and also the colocalization of both enzymes at all
      life stages suggest a more general purpose of the complex, e.g. the synthesis of
      neuroactive steroids or the catabolism of neurotoxic steroids, rather than
      control of reproductive functions.

PMID- 11238529
TI  - Interleukin-1beta regulates urokinase plasminogen activator (u-PA), u-PA
      receptor, soluble u-PA receptor, and plasminogen activator inhibitor-1 messenger
      ribonucleic acid expression in cultured human endometrial stromal cells.
AB  - The interleukin-1 (IL-1) system plays an integral role in local intercellular
      interactions during implantation. In addition, the plasminogen activator system,
      especially urokinase plasminogen activator (u-PA), plasminogen activator
      inhibitor (PAI-1), and u-PA receptor (u-PAR), are crucial during embryo
      implantation. Decidualization and implantation are complex processes dependent
      upon several proteases, including u-PA, and IL-1 is known to affect PA activity
      in several cell types. We investigated the role of IL-1beta in regulating u-PA,
      PAI-1, u-PAR, and soluble u-PAR messenger ribonucleic acid (mRNA) expression in
      cultured human endometrial stromal cells using quantitative competitive PCR. For
      confirmation of the mRNA data, we measured PAI-1 and u-PAR protein by enzyme
      linked immunosorbent assay. Confluent stromal cell cultures treated with
      progesterone and estradiol for 9 days were stimulated with IL-1beta, and IL-1beta
      plus IL-1beta antibody for an additional 24 h. Total RNA was extracted, reverse
      transcribed, and coamplified using quantitative and competitive PCR with internal
      standards. IL-1beta increased PAI-1, u-PAR, and soluble u-PAR expression in a
      dose-dependent manner, and this result was reversed by anti-IL-1beta antibody
      treatment. u-PA mRNA expression was not dependent on IL-1beta. These results
      suggest that IL-1 may be important in regulating PAI-1 and u-PAR during stromal
      cell decidualization before implantation.

PMID- 11238531
TI  - Infiltration of differentiated thyroid carcinoma by proliferating lymphocytes is
      associated with improved disease-free survival for children and young adults.
AB  - An immune response directed against thyroid cancer might be important in
      preventing metastasis and recurrence. This idea is supported by previous
      observations showing that adults with autoimmune thyroiditis or lymphocytic
      infiltration surrounding papillary thyroid carcinoma (PTC) have improved disease
      free survival. The long-term outcome for differentiated thyroid cancer is even
      more favorable for children and young adults. If the immune response is
      important, we hypothesized that tumor-associated lymphocytes with a high
      proliferation index would be found in thyroid cancers from children and young
      adults and would be associated with improved disease-free survival. Using
      immunohistochemistry, we examined 39 childhood PTC, 9 follicular thyroid
      carcinomas, 2 medullary thyroid carcinomas, 11 benign thyroid lesions, and 2
      normal thyroid glands for the presence of lymphocytes (leukocyte common antigen)
      and lymphocyte proliferation (proliferating cell nuclear antigen, Ki-67). The
      majority of PTC (65%) and follicular thyroid carcinomas (75%) from children and
      young adults contained lymphocytes in the immediate vicinity of thyroid cancers,
      but only 7 (18%) patients with PTC also had a diagnosis of autoimmune
      thyroiditis. Disease-free survival did not correlate with the presence or number
      of lymphocytes per high power field. In contrast, disease-free survival was
      significantly improved (P = 0.01) for thyroid cancers with the greatest number of
      Ki-67-positive lymphocytes per high power field. The number of lymphocytes per
      high powered field was greater for multifocal PTC (P: = 0.023), and the number of
      proliferating lymphocytes was greatest for PTC with regional lymph node
      involvement (30.5 +/- 12.3 vs. 6.8 +/- 5.0; P = 0.047). We conclude that
      proliferation of tumor-associated lymphocytes is associated with improved disease
      free survival for children and young adults with thyroid cancer.

PMID- 11238530
TI  - Leptin is associated with increased prostate cancer risk: a nested case-referent
      study.
AB  - A Western lifestyle has been implicated in the pathogenesis of prostate cancer.
      However, no clear association between obesity and prostate cancer has been shown.
      Leptin may stimulate prostate growth and angiogenesis, and receptors for leptin
      are present in the prostate. Leptin may, thus, be associated with increased risk
      of prostate cancer. One hundred forty-nine men with prostate cancer were
      identified (together with 298 matched referents) who, before diagnosis, had
      participated in population-based health surveys in Northern Sweden. Blood
      pressure, body mass index, and use of tobacco were recorded. Leptin, insulin,
      insulin-like growth factor I (IGF-I), IGF-I-binding proteins 1-3, testosterone,
      and sex hormone-binding globulin were analyzed in stored samples. Their
      influences on prostate cancer were estimated by conditional logistic regression
      analysis. Prostate cancer specimens were investigated for immunoreactivity for
      the leptin receptor. Relative risk (95% confidence intervals) estimates of
      prostate cancer over the quintiles of leptin were 1.0, 2.1 (1.1-4.1), 2.6 (1.4
      4.8), 1.4 (0.7-2.7), and 1.6 (0.8-3.2). Adjustments for metabolic variables,
      testosterone, and IGF-I and its binding proteins did not attenuate this increased
      risk. Immunoreactivity for the leptin receptor was detected in normal, high-grade
      prostatic intraepithelial neoplasia lesions and malignant prostatic epithelium.
      Moderately elevated plasma leptin concentrations are associated with later
      development of prostate cancer. This may be due to direct effects of leptin on
      prostatic intraepithelial neoplasia lesions, or to indirect actions through other
      mechanisms. A critical fat mass related to an interior milieu favorable for
      prostate cancer development seems to exist, because intermediate but not high
      leptin levels are related to prostate cancer risk.

PMID- 11238532
TI  - Multiple allelic deletions and intratumoral genetic heterogeneity in men1
      pancreatic tumors.
AB  - Multiple endocrine neoplasia type 1 (MEN1) is an inherited syndrome with multiple
      tumors of the endocrine pancreas, the parathyroid, the pituitary, and other
      tissues. The MEN1 gene at 11q13 is homozygously mutated in the majority of MEN1
      tumors. Here we present a genome-wide loss of heterozygosity (LOH) screening of
      23 pancreatic lesions, one duodenal tumor, and one thymic carcinoid from 13 MEN1
      patients. Multiple allelic deletions were found. Fractional allelic loss varied
      from 6-75%, mean 31%. All pancreatic tumors displayed LOH on chromosome 11,
      whereas the frequency of losses for chromosomes 3, 6, 8, 10, 18, and 21 was over
      30%. Different lesions from individual patients had discrepant patterns of LOH.
      Intratumoral heterogeneity was revealed, with chromosome 6 and 11 deletions in
      most tumor cells, whereas other chromosomal loci were deleted in portions of the
      analyzed tumor. Chromosome 6 deletions were mainly found in lesions from patients
      with malignant features. Fractional allelic loss did not correlate to malignancy
      or to tumor size. Our findings indicate that MEN1 pancreatic tumors fail to
      maintain DNA integrity and demonstrate signs of chromosomal instability.

PMID- 11238533
TI  - Urocortin and corticotropin-releasing factor receptor expression in normal
      cycling human ovaries.
AB  - Urocortin is a member of the CRF neuropeptide family and has a 43% homology to
      CRF in amino acid sequence. Urocortin has been found to bind with high affinity
      to CRF receptors. CRF has been detected in the human ovary and has been
      demonstrated to suppress ovarian steroidogenesis in vitro. In this study we
      examined urocortin and CRF receptor expression in normal cycling human ovaries,
      using immunohistochemistry and RT-PCR. Normal cycling human ovaries were obtained
      at oophorectomy and hysterectomy from patients who underwent surgery for cervical
      cancer or myoma uteri. Intense urocortin immunoreactivity was detected in
      luteinized thecal cells of regressing corpora lutea, in which only luteinized
      thecal cells have the capacity for steroidogenesis. Immunoreactive urocortin was
      also detected in luteinized granulosa and thecal cells of functioning corpora
      lutea, in which both cell components are capable of producing steroids. RT-PCR
      analyses revealed that messenger ribonucleic acid levels for urocortin, CRF, and
      CRF receptor type 1 and type 2alpha were significantly higher in the regressing
      corpus luteum than in the functioning corpus luteum. The spatial and temporal
      immunolocalization patterns of CRF receptor were similar to those of urocortin.
      These results suggest that urocortin is locally synthesized in steroidogenic
      luteal cells and acts on them as an autocrine and/or paracrine regulator of
      ovarian steroidogenesis, especially during luteal regression.

PMID- 11238534
TI  - Estrogen receptor beta, but not estrogen receptor alpha, is present in the
      vascular endothelium of the human and nonhuman primate endometrium.
AB  - Estrogen action is dependent upon the presence of specific ligand-activated
      receptors in target tissues. The aim of the present experiments was to compare
      the spatial and temporal pattern of expression of estrogen receptor beta (ERbeta)
      with that of ERalpha in full thickness endometrial samples (from the superficial
      to the basal zone) obtained from both women and rhesus macaques.
      Immunohistochemical localization with specific antibodies revealed that ERalpha
      and ERbeta were both expressed in nuclei of the glands and stroma. Consistent
      with previous studies, expression of ERalpha declined in the glands and stroma of
      the functionalis during the secretory phase. The luminal epithelium also
      displayed positive immunoreactivity for ERbeta. Expression of ERbeta declined in
      glandular cell nuclei, but not stroma, within the functionalis during the late
      secretory phase. Levels of expression of ERalpha and ERbeta in all cellular
      compartments remained unchanged in the basalis. Both receptor subtypes were
      detected on Western blots using proteins extracted from uterine samples obtained
      throughout the menstrual cycle. There was a striking contrast between the pattern
      of expression of ERalpha and ERbeta in the vascular endothelium and the
      perivascular cells surrounding endometrial blood vessels; only ERbeta was present
      in the endothelial cell population, although both forms of ER were expressed in
      perivascular cells. We conclude that estrogen action(s) within the vascular
      endothelium in the endometrium may be mediated via direct binding to the ERbeta
      isoform and that these cells could therefore be a target for agonists or
      antagonists that selectively target the beta form of the ER.

PMID- 11238535
TI  - Presence of estrogen receptor beta in the human endometrium through the cycle:
      expression in glandular, stromal, and vascular cells.
AB  - The recent discovery of a new isoform of estrogen receptor (ER) beta has prompted
      the reexamination of estrogen action on target organs. Here, we describe the
      endometrial expression of human ERbeta and compare its distribution with that of
      ERalpha in the endometrial functional zone. Using immunocytochemistry with well
      characterized polyclonal antibodies against ERbeta, we have detected specific
      ERbeta expression in all endometrial compartments (glandular, stromal, and
      vascular); the specificity of the immunostaining is confirmed by lack of staining
      of the uterine sections with anti-ERbeta antibodies previously incubated with
      peptide preparation. The highest levels of ERbeta expression are observed in
      epithelial cells during the periovulatory period (days 14 and 15), as well as in
      stromal cells and cells of the vascular wall in the late-secretory phase; both
      smooth muscle cells and endothelial cells express ERbeta, as deduced from
      immunocytochemistry and RT-PCR analysis. ERbeta staining is usually low compared
      with that of ERalpha, except at days 24-26. The presence of ERbeta in
      decidualized stromal cells is deduced from immunocytochemistry using antismooth
      alpha-actin and anti-ERbeta antibodies or from RT-PCR analysis of ERbeta and
      insulin-like growth factor-BP transcripts in the same cells; the presence of
      ERbeta-positive stromal cells located close to vascular smooth muscle cells
      during this period suggests some specific role of this receptor during
      decidualization. ERalpha is also present in the cells of the endometrial vascular
      wall, in addition to the nuclei of glandular epithelial and stromal cells.
      Vascular ERalpha expression is highest during the periovulatory period,
      suggesting a regulation by estradiol, and a role in vascular function. Moreover,
      different variations of ERbeta and ERalpha in arterioles might have implications
      for the modulation of vascular function, possibly of vascular tone, during the
      menstrual cycle. Finally, these data suggest that ERbeta may have important roles
      in endometrial function, in addition to the well known role of ERalpha in
      endometrial proliferation and differentiation.

PMID- 11238536
TI  - Interleukin (IL)-1beta regulation of IL-1beta and IL-1 receptor antagonist
      expression in cultured human endometrial stromal cells.
AB  - The interleukin (IL)-1 system is a major regulator of local cellular interactions
      during embryonic implantation. Because IL-1beta and IL receptor antagonist (IL
      1ra) are both expressed in human endometrium, we hypothesized that an appropriate
      ratio of IL-1beta to IL-1ra might favor the process of embryo implantation.
      Therefore, we investigated IL-1 regulation of the quantitative ratio of IL
      1beta/IL-1ra messenger RNA (mRNA) expression in human endometrial stromal cells
      using quantitative competitive PCR, as well as intracellular protein expression
      after stromal cell solubilization. Confluent stromal cell cultures were
      stimulated with human IL-1beta (0-1000 IU/mL) for 24 h. After 24 h, total RNA was
      extracted, reverse transcribed, and coamplified by PCR with a defined amount of
      internal standard. The quantitative ratio was determined by the density of target
      to the internal standard. After culture with IL-1beta for 24 and 48 h, stromal
      cells were solubilized, and the intracellular protein levels of IL-1beta and IL
      1ra were measured by enzyme-linked immunosorbent assay. The IL-1beta and IL-1ra
      mRNA were both up-regulated, and IL-1R tI mRNA was down-regulated, by IL-1beta in
      a dose-dependent manner. The quantitative ratio of IL-1beta to IL-1ra mRNA was
      constant with the presence of increasing concentrations of IL-1beta (1-1000
      IU/mL). IL-1beta and IL-1ra protein was not detected in conditioned media of
      cultures before addition of IL-1beta. IL-1beta and IL-1ra protein levels
      increased with increasing amounts of IL-1beta after solubilization of stromal
      cells. The IL-1beta was detectable after 12 h of culture, in comparison with IL
      1ra, which was detectable after 24 h of IL-1beta stimulation. These results
      suggest that IL-1 may play a crucial role in embryo-maternal interaction by
      regulating stromal cell expression of IL-1beta and IL-1ra, resulting in an
      appropriate ratio during the process of embryonic implantation.

PMID- 11238537
TI  - Analysis of the P3 promoter of the human parathyroid hormone (PTH)/PTH-related
      peptide receptor gene in pseudohypoparathyroidism type 1b.
AB  - Hypocalcemia and hyperphosphatemia caused by PTH resistance are the only
      discernible abnormalities in pseudohypoparathyroidism type 1b (PHP-1b). Because
      of the selective resistance toward PTH, inactivating mutations in its receptor,
      the PTH/PTH-related peptide receptor (PTHR1), were thought to be responsible for
      PHP-1b. However, gene abnormalities responsible for PHP-1b have not been
      identified in the coding region and well conserved promoters (P1 and P2) of the
      PTHR1 gene. The purpose of the present study was to analyze the structure of the
      P3 promoter, the main promoter of the human PTHR1 gene in kidney, in patients
      with PHP-1b. Southern analysis of genomic DNA from lymphoblastoid cell lines of
      eight nonfamilial patients with PHP-1b revealed neither gross rearrangements nor
      methylation abnormalities in the P3 promoter region of the PTHR1 gene. Sequencing
      revealed no abnormalities in the P3 promoter region, although one patient was
      homozygous for an (AAAG)n polymorphic variant. In conclusion, despite the
      selective resistance toward PTH in the kidney, which mainly uses the PTHR1 P3
      promoter, PHP-1b in eight cases is not associated with structural abnormalities
      in this promoter. This study also indicates that inactivation of the P3 promoter
      is not achieved by methylation as tested in patients' genomic DNA from
      lymphoblastoid cell lines. The influence of alterations in the polymorphic A-rich
      repeat sequence on promoter activity warrants further study.

PMID- 11238538
TI  - A prevalent polymorphism in the promoter of the UCP3 gene and its relationship to
      body mass index and long term body weight change in the Danish population.
AB  - Variability of the uncoupling protein 3 (UCP3) promoter has been associated with
      increased body mass index (BMI) and altered lipid profiles. Here we tested the
      hypothesis that variation of the UCP3 promoter is associated with either juvenile
      or maturity-onset obesity or body weight change over a 26-yr follow-up among
      Danish subjects. Mutation screening of approximately 1 kb 5' upstream of the UCP3
      gene revealed one previously described -55 C-->T variant. The frequency of the
      polymorphism was evaluated by restriction fragment length polymorphism analysis
      in four groups of subjects: 1) a group of 744 obese Danish men who at the draft
      board examinations had a body mass index (BMI) of at least 31 kg/m(2), 2) a
      randomly selected control group consisting of 857 draftees, 3) 258 middle-aged
      subjects, and 4) 409 60-yr-old subjects. The frequency of the T allele was 26.0%
      (95% confidence interval, 23.8-28.2%) among the obese draftees and 26.9% (24.8
      29.0%) in the control group (P = 0.6). The variant was not associated with BMI at
      a young age or with weight gain after a 26-yr follow-up. The frequency of the T
      allele was 29.5% (25.6-33.4%) in the middle-aged group and 25.8% (22.8-28.8%)
      among the 60-yr-old subjects. The polymorphism was not associated with increased
      BMI or percent body fat in these 2 groups. It is concluded that this variant does
      not play a major role in the development of common obesity among Danish subjects.

PMID- 11238539
TI  - Insulin sensitivity regulates autonomic control of heart rate variation
      independent of body weight in normal subjects.
AB  - It is unclear whether insulin sensitivity independent of body weight regulates
      control of heart rate variation (HRV) by the autonomic nervous system. Insulin
      action on whole-body glucose uptake (M-value) and heart rate variability were
      measured in 21 normal men. The subjects were divided into 2 groups [normally
      insulin sensitive (IS, 8.0 +/- 0.4 mg/kg.min) and less insulin sensitive (IR, 5.1
      +/- 0.3 mg/kg.min)] based on their median M-value (6.2 mg/kg x min). Spectral
      power analysis of heart rate variability was performed in the basal state and
      every 30 min during the insulin infusion. The IS and IR groups were comparable,
      with respect to age (27 +/- 2 vs. 26 +/- 2 yr), body mass index (22 +/- 1 vs. 23
      +/- 1 kg/m(2)), body fat (13 +/- 1 vs. 13 +/- 1%), systolic (121 +/- 16 vs. 117
      +/- 14 mm Hg) and diastolic (74 +/- 11 vs. 73 +/- 11 mm Hg) blood pressures, and
      fasting plasma glucose (5.4 +/- 0.1 vs. 5.5 +/- 0.1 mmol/L) concentrations.
      Fasting plasma insulin was significantly higher in the IR (30 +/- 4 pmol/L) than
      in the IS (17 +/- 3 pmol/L, P < 0.05) group. In the IS group, insulin
      significantly increased the normalized low-frequency (LFn) component, a measure
      of predominantly sympathetic nervous system activity, from 36 +/- 5 to 48 +/- 4
      normalized units (nu; 0 vs. 30-120 min, P < 0.001); whereas the normalized high
      frequency (HFn) component, a measure of vagal control of HRV, decreased from 66
      +/- 9 to 48 +/- 5 nu (P < 0.001). No changes were observed in either the
      normalized LF component [35 +/- 5 vs. 36 +/- 2 nu, not significant (NS)] or the
      normalized HF component (52 +/- 6 vs. 51 +/- 4 nu, NS) in the IR group. The ratio
      LF/HF, a measure of sympathovagal balance, increased significantly in the IS
      group (0.92 +/- 0.04 vs. 1.01 +/- 0.04, P < 0.01) but remained unchanged in the
      IR group (0.91 +/- 0.04 vs. 0.92 +/- 0.03, NS). Heart rate and systolic and
      diastolic blood pressures remained unchanged during the insulin infusion in both
      groups. We conclude that insulin acutely shifts sympathovagal control of HRV
      toward sympathetic dominance in insulin-sensitive, but not in resistant,
      subjects. These data suggest that sympathetic overactivity is not a consequence
      of hyperinsulinemia.

PMID- 11238540
TI  - Vanadyl sulfate improves hepatic and muscle insulin sensitivity in type 2
      diabetes.
AB  - Vanadyl sulfate (VOSO(4)) is an oxidative form of vanadium that in vitro and in
      animal models of diabetes has been shown to reduce hyperglycemia and insulin
      resistance. Small clinical studies of 2- to 4-week duration in type 2 diabetes
      (T2DM) have led to inconsistent results. To define its efficacy and mechanism of
      action, 11 type 2 diabetic patients were treated with VOSO(4) at a higher dose
      (150 mg/day) and for a longer period of time (6 weeks) than in previous studies.
      Before and after treatment we measured insulin secretion during an oral glucose
      tolerance test, and endogenous glucose production (EGP) and whole body insulin
      mediated glucose disposal using the euglycemic insulin clamp technique combined
      [3-(3)H]glucose infusion. Treatment significantly improved glycemic control:
      fasting plasma glucose (FPG) decreased from 194 +/- 16 to 155 +/- 15 mg/dL,
      hemoglobin A(1c) decreased from 8.1 +/- 0.4 to 7.6 +/- 0.4%, and fructosamine
      decreased from 348 +/- 26 to 293 +/- 12 micromol/L (all P < 0.01) without any
      change in body weight. Diabetics had an increased rate of EGP compared with
      nondiabetic controls (4.1 +/- 0.2 vs. 2.7 +/- 0.2 mg/kg lean body mass.min; P<
      0.001), which was closely correlated with FPG (r = 0.56; P< 0.006). Vanadyl
      sulfate reduced EGP by about 20% (P< 0.01), and the decline in EGP was correlated
      with the reduction in FPG (r = 0.60; P< 0.05). Vanadyl sulfate also caused a
      modest increase in insulin-mediated glucose disposal (from 4.3 +/- 0.4 to 5.1 +/-
      0.6 mg/kg lean body mass x min; P< 0.03), although the improvement in insulin
      sensitivity did not correlate with the decline in FPG after treatment (r = -0.16;
      P = NS). Vanadyl sulfate treatment lowered the plasma total cholesterol (223 +/-
      14 vs. 202 +/- 16 mg/dL; P < 0.01) and low density lipoprotein cholesterol (141
      +/- 14 vs. 129 +/- 14 mg/dL; P < 0.05), whereas 24-h ambulatory blood pressure
      was unaltered. We conclude that VOSO(4) at maximal tolerated doses for 6 weeks
      improves hepatic and muscle insulin sensitivity in T2DM. The glucose-lowering
      effect of VOSO(4) correlated well with the reduction in EGP, but not with insulin
      mediated glucose disposal, suggesting that liver, rather than muscle, is the
      primary target of VOSO(4) action at therapeutic doses in T2DM.

PMID- 11238541
TI  - Tissue-specific dysregulation of cortisol metabolism in human obesity.
AB  - Cortisol has been implicated as a pathophysiological mediator in idiopathic
      obesity, but circulating cortisol concentrations are not consistently elevated.
      The tissue-specific responses to cortisol may be influenced as much by local
      prereceptor metabolism as by circulating concentrations. For example, in liver
      and adipose tissue cortisol is regenerated from inactive cortisone by 11beta
      hydroxysteroid dehydrogenase type 1 (11beta-HSD1). In obese Zucker rats 11beta
      HSD1 activity is reduced in liver but enhanced in adipose tissue. This study
      addressed whether the same tissue-specific disruption of cortisol metabolism
      occurs in human obesity. 34 men were recruited from the MONICA population study
      in Northern Sweden to represent a wide range of body composition and insulin
      insensitivity. Plasma cortisol was measured at 0830h and 1230h, after overnight
      low-dose dexamethasone suppression, after intravenous corticotropin releasing
      hormone (CRH), and after oral cortisone administration. Urinary cortisol
      metabolites were measured in a 24 h sample. A subcutaneous fat biopsy was
      obtained from 16 participants to measure cortisol metabolism in vitro. Higher
      body mass index was associated with increased total cortisol metabolite excretion
      (r = 0.47, p < 0.01), but lower plasma cortisol at 1230 h and after
      dexamethasone, and no difference in response to CRH. Obese men excreted a greater
      proportion of glucocorticoid as metabolites of cortisone rather than cortisol (r
      = 0.43, p < 0.02), and converted less cortisone to cortisol after oral
      administration (r = 0.49, p < 0.01), suggesting impaired hepatic 11beta-HSD1
      activity. By contrast, in vitro 11beta-HSD1 activity in subcutaneous adipose
      tissue was markedly enhanced in obese men (r = 0.66, p < 0.01). We conclude that
      in obesity, reactivation of cortisone to cortisol by 11beta-HSD1 in liver is
      impaired, so that plasma cortisol levels tend to fall, and there may be a
      compensatory increase in cortisol secretion mediated by a normally functioning
      hypothalamic-pituitary-adrenal axis. However, changes in 11beta-HSD1 are tissue
      specific: strikingly enhanced reactivation of cortisone to cortisol in
      subcutaneous adipose tissue may exacerbate obesity; and it may be beneficial to
      inhibit this enzyme in adipose tissue in obese patients.

PMID- 11238542
TI  - Raloxifene affects brain activation patterns in postmenopausal women during
      visual encoding.
AB  - Recent brain imaging studies have shown that estrogens alter brain activation
      patterns upon working memory tasks in postmenopausal women. Estrogens, however,
      have many systemic side effects. We investigated the effect of the Selective
      estrogen receptor modulator (SERM) raloxifene on brain activation patterns during
      a memory task in postmenopausal women with functional magnetic resonance imaging
      (fMRI). Twenty postmenopausal and right handed women (mean age 65.7 years; SD
      3.0) were included in this double blind, placebo controlled and randomized study.
      Whole brain fMRI was performed before and after three months of daily treatment
      with raloxifene 60 mg or placebo. Each scanning session consisted of a visual
      encoding task, a recognition test and a simple photic simulation test. Data
      analyses was performed with SPM99b software. Specific regions of interest for the
      tasks were defined based in previous experiments. Visual encoding activated the
      ventral route, posterior medial temporal lobe and frontal cortex in both groups.
      Treatment interactions for raloxifene compared to placebo were a decrease in
      activation in the left parahippocampal gyrus and left lingual gyrus, an increase
      in activation in the right superior frontal gyrus. The mean recognition test and
      the simple photic stimulation test showed no treatment interactions. Our results
      show that raloxifene affects brain activation patterns upon visual encoding in
      postmenopausal women.

PMID- 11238543
TI  - Allopregnanolone assays.

PMID- 11238544
TI  - Defective cortisone 11-oxoreductase activity?

PMID- 11238548
TI  - Smell, taste, head trauma, and hypopituitarism.

PMID- 11238549
TI  - Chernobyl thyroid tumor bank.

PMID- 11238550
TI  - Different significance of ret/PTC(1) and ret/PTC(3) rearrangements in thyroid
      carcinogenesis: lesson from two subgroups of patients with papillary thyroid
      carcinomas showing the highest incidence of ret/PTC activation.

PMID- 11238551
TI  - Metformin and the polycystic ovary syndrome.

PMID- 11238552
TI  - The nature and consequence of genetic variability within Mycobacterium
      tuberculosis.

PMID- 11238553
TI  - Pathogenesis and evolution of virulence in enteropathogenic and enterohemorrhagic
      Escherichia coli.

PMID- 11238554
TI  - MHC class II genotype and the control of viremia in HIV-1-infected individuals on
      highly active antiretroviral therapy.

PMID- 11238555
TI  - How much help does a vaccine-induced T-cell response need?

PMID- 11238556
TI  - Self-antigen-presenting cells expressing diabetes-associated autoantigens exist
      in both thymus and peripheral lymphoid organs.
AB  - Recent reports indicate that genes with tissue-restricted expression, including
      those encoding the type 1 diabetes autoantigens insulin, glutamic acid
      decarboxylase (GAD), and the tyrosine-phosphatase-like protein IA-2 (or ICA512),
      are transcribed in the thymus. The reported modulation of diabetes susceptibility
      by genetically determined differences in thymic insulin levels and studies in
      transgenic mice provide correlative and functional evidence that thymic
      expression of peripheral proteins is crucial for immunological self-tolerance.
      However, there are no specific data about the existence, tissue distribution,
      phenotype, and function of those cells that express insulin and other self
      antigens in the human thymus. We find that the human thymus harbors specialized
      cells synthesizing (pro)insulin, GAD, and IA-2, mainly localized in the medulla,
      and we demonstrate such cells also in peripheral lymphoid organs (spleen and
      lymph nodes). Phenotypic analysis qualifies these cells as antigen-presenting
      cells (APCs), including both dendritic cells and macrophages. These cells often
      appear surrounded by apoptotic lymphocytes, both in thymus and spleen, and may
      therefore be involved in the deletion of autoreactive lymphocytes. Our findings
      demonstrate the existence of, and define the tissue distribution and phenotype
      of, a novel subset of APCs expressing self-antigens in human lymphoid organs that
      appear to be involved in the regulation of self-tolerance throughout life.

PMID- 11238557
TI  - Hepatic cholesterol metabolism and resistance to dietary cholesterol in LXRbeta
      deficient mice.
AB  - The nuclear oxysterol-receptor paralogues LXRalpha and LXRbeta share a high
      degree of amino acid identity and bind endogenous oxysterol ligands with similar
      affinities. While LXRalpha has been established as an important regulator of
      cholesterol catabolism in cholesterol-fed mice, little is known about the
      function of LXRbeta in vivo. We have generated mouse lines with targeted
      disruptions of each of these LXR receptors and have compared their responses to
      dietary cholesterol. Serum and hepatic cholesterol levels and lipoprotein
      profiles of cholesterol-fed animals revealed no significant differences between
      LXRbeta(-/-) and wild-type mice. Steady-state mRNA levels of 3-hydroxy-3
      methylglutaryl coenzyme A reductase, farnesyl diphosphate synthase, and squalene
      synthase were increased in LXRbeta(-/-) mice compared with LXRbeta(+/+) mice,
      when fed standard chow. The mRNA levels for cholesterol 7alpha-hydroxylase,
      oxysterol 7alpha-hydroxylase, sterol 12alpha-hydroxylase, and sterol 27
      hydroxylase, respectively, were comparable in these strains, both on standard and
      2% cholesterol chow. Our results indicate that LXRbeta(-/-) mice - in contrast to
      LXRalpha(-/-) mice - maintain their resistance to dietary cholesterol, despite
      subtle effects on the expression of genes coding for enzymes involved in lipid
      metabolism. Thus, our data indicate that LXRbeta has no complete overlapping
      function compared with LXRalpha in the liver.

PMID- 11238559
TI  - Increased sensitivity to dextran sodium sulfate colitis in IRE1beta-deficient
      mice.
AB  - The epithelial cells of the gastrointestinal tract are exposed to toxins and
      infectious agents that can adversely affect protein folding in the endoplasmic
      reticulum (ER) and cause ER stress. The IRE1 genes are implicated in sensing and
      responding to ER stress signals. We found that epithelial cells of the
      gastrointestinal tract express IRE1beta, a specific isoform of IRE1. BiP protein,
      a marker of ER stress, was elevated in the colonic mucosa of IRE1beta(-/-) mice,
      and, when exposed to dextran sodium sulfate (DSS) to induce inflammatory bowel
      disease, mutant mice developed colitis 3-5 days earlier than did wild-type or
      IRE1beta(+/-) mice. The inflammation marker ICAM-1 was also expressed earlier in
      the colonic mucosa of DSS-treated IRE1beta(-/-) mice, indicating that the
      mutation had its impact early in the inflammatory process, before the onset of
      mucosal ulceration. These findings are consistent with a model whereby
      perturbations in ER function, which are normally mitigated by the activity of
      IRE1beta, participate in the development of colitis.

PMID- 11238558
TI  - CD28-independent induction of experimental autoimmune encephalomyelitis.
AB  - Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated disease
      initiated by antigen-specific CD4(+) T cells. Signaling through CD28 is a
      critical second signal for activation of T cells, and CD28 knockout (CD28KO) mice
      have been reported to be resistant to induction of EAE. We now report that CD28KO
      mice have no intrinsic defect in mediating disease, because they developed EAE
      after passive transfer of primed T cells. After immunization, peripheral T cells
      from CD28KO mice were primed and developed memory phenotype, but had decreased
      antigen-specific IFN-gamma production as compared with cells from wild-type (WT)
      animals. Reimmunization of CD28KO mice brought out clinical disease and increased
      IFN-gamma production in vitro. Pathologically, there were cellular infiltrates in
      the central nervous system, in contrast to single-immunized mice. We show
      furthermore that blocking B7-1 or CTLA4, but not B7-2, in CD28KO mice induces
      disease after a single immunization. Thus, EAE can be induced in animals lacking
      CD28-dependent costimulation, suggesting that alternative costimulatory pathways
      were used. Blocking the OX40-OX40L costimulatory pathway differentially affected
      disease induction in CD28KO mice as compared with WT controls. Our data show that
      EAE may develop in the absence of CD28 T-cell costimulation. These findings have
      implications for therapies aimed at blocking costimulatory signals in autoimmune
      diseases.

PMID- 11238560
TI  - Bonzo/CXCR6 expression defines type 1-polarized T-cell subsets with extralymphoid
      tissue homing potential.
AB  - Chemokine receptor expression is finely controlled during T-cell development. We
      show that newly identified chemokine receptor Bonzo/CXCR6 is expressed by subsets
      of Th1 or T-cytotoxic 1 (Tc1) cells, but not by Th2 or Tc2 cells, establishing
      Bonzo as a differential marker of polarized type 1 T cells in vitro and in vivo.
      Priming of naive T cells by dendritic cells induces expression of Bonzo on T
      cells. IL-12 enhances this dendritic cell-dependent upregulation, while IL-4
      inhibits it. In blood, 35-56% of Bonzo+ CD4 T cells are Th1 cells, and 60-65% of
      Bonzo+ CD8 T cells are Tc1 cells, while few Bonzo+ cells are type 2 T cells.
      Almost all Bonzo+ Tc1 cells contain preformed granzyme A and display cytotoxic
      effector phenotype. Most Bonzo+ T cells lack L-selectin and/or CCR7, homing
      receptors for lymphoid tissues. Instead, Bonzo+ T cells are dramatically enriched
      among T cells in tissue sites of inflammation, such as rheumatoid joints and
      inflamed livers. Bonzo may be important in trafficking of effector T cells that
      mediate type 1 inflammation, making it a potential target for therapeutic
      modulation of inflammatory diseases.

PMID- 11238561
TI  - Activation of the murine EP3 receptor for PGE2 inhibits cAMP production and
      promotes platelet aggregation.
AB  - The importance of arachidonic acid metabolites (termed eicosanoids), particularly
      those derived from the COX-1 and COX-2 pathways (termed prostanoids), in platelet
      homeostasis has long been recognized. Thromboxane is a potent agonist, whereas
      prostacyclin is an inhibitor of platelet aggregation. In contrast, the effect of
      prostaglandin E2 (PGE2) on platelet aggregation varies significantly depending on
      its concentration. Low concentrations of PGE2 enhance platelet aggregation,
      whereas high PGE2 levels inhibit aggregation. The mechanism for this dual action
      of PGE2 is not clear. This study shows that among the four PGE2 receptors (EP1
      EP4), activation of EP3 is sufficient to mediate the proaggregatory actions of
      low PGE2 concentration. In contrast, the prostacyclin receptor (IP) mediates the
      inhibitory effect of higher PGE2 concentrations. Furthermore, the relative
      activation of these two receptors, EP3 and IP, regulates the intracellular level
      of cAMP and in this way conditions the response of the platelet to aggregating
      agents. Consistent with these findings, loss of the EP3 receptor in a model of
      venous inflammation protects against formation of intravascular clots. Our
      results suggest that local production of PGE2 during an inflammatory process can
      modulate ensuing platelet responses.

PMID- 11238562
TI  - Helicobacter pylori strain-specific differences in genetic content, identified by
      microarray, influence host inflammatory responses.
AB  - Helicobacter pylori enhances the risk for ulcer disease and gastric cancer, yet
      only a minority of H. pylori-colonized individuals develop disease. We examined
      the ability of two H. pylori isolates to induce differential host responses in
      vivo or in vitro, and then used an H. pylori whole genome microarray to identify
      bacterial determinants related to pathogenesis. Gastric ulcer strain B128 induced
      more severe gastritis, proliferation, and apoptosis in gerbil mucosa than did
      duodenal ulcer strain G1.1, and gastric ulceration and atrophy occurred only in
      B128+ gerbils. In vitro, gerbil-passaged B128 derivatives significantly increased
      IL-8 secretion and apoptosis compared with G1.1 strains. DNA hybridization to the
      microarray identified several strain-specific differences in gene composition
      including a large deletion of the cag pathogenicity island in strain G1.1.
      Partial and complete disruption of the cag island in strain B128 attenuated
      induction of IL-8 in vitro and significantly decreased gastric inflammation in
      vivo. These results indicate that the ability of H. pylori to regulate epithelial
      cell responses related to inflammation depends on the presence of an intact cag
      pathogenicity island. Use of an H pylori whole genome microarray is an effective
      method to identify differences in gene content between H. pylori strains that
      induce distinct pathological outcomes in a rodent model of H. pylori infection.

PMID- 11238563
TI  - Translocated EspF protein from enteropathogenic Escherichia coli disrupts host
      intestinal barrier function.
AB  - The mechanisms by which enteropathogenic Escherichia coli (EPEC), an important
      cause of diarrhea among infants in developing countries, induce symptoms are not
      defined. EPEC have a type III secretion system required for characteristic
      attaching and effacing changes that modify the cytoskeleton and apical surface of
      host cells. Infection of polarized intestinal epithelial cell monolayers by EPEC
      leads to a loss of transepithelial electrical resistance, which also requires the
      type III secretion system. We demonstrate here that EspF, a protein that is
      secreted by EPEC via the type III secretion system, is not required for
      quantitatively and qualitatively typical attaching and effacing lesion formation
      in intestinal epithelial cells. However, EspF is required in a dose-dependent
      fashion for the loss of transepithelial electrical resistance, for increased
      monolayer permeability, and for redistribution of the tight junction-associated
      protein occludin. Furthermore, the analysis of EPEC strains expressing EspF
      adenylate cyclase fusion proteins indicates that EspF is translocated via the
      type III secretion system to the cytoplasm of host cells, a result confirmed by
      immunofluorescence microscopy. These studies suggest a novel role for EspF as an
      effector protein that disrupts intestinal barrier function without involvement in
      attaching and effacing lesion formation.

PMID- 11238564
TI  - Amelioration of collagen-induced arthritis by thrombin inhibition.
AB  - The deleterious role of fibrin deposition in arthritic joints prompted us to
      explore the effect of the thrombin inhibition on the course of collagen-induced
      arthritis (CIA) in the mouse. CIA was induced in male DBA/1J mice using native
      chicken type II collagen. The thrombin inhibitor polyethyleneglycol-hirudin (PEG
      hirudin) was given for 16 days, starting 20 days after the first immunization
      (preventive treatment) or at the onset of clinical signs of arthritis (curative
      treatment). All the mice treated with PEG-hirudin had a significantly prolonged
      clotting time compared with control mice. PEG-hirudin, administered in a
      preventive way, led to significantly reduced incidence and severity of CIA during
      most of the treatment period, as assessed by clinical scoring. Accordingly,
      histological features showed a significant diminution of synovial hyperplasia in
      PEG-hirudin-treated mice compared with untreated mice. There was also a
      significant downmodulation of the synovial proinflammatory IL-1beta and IL-12p35
      cytokine mRNAs in treated mice. Intra-articular fibrin, evaluated by
      immunohistochemistry, was significantly reduced in treated mice compared with
      control mice and correlated with both clinical and histological scorings. Most
      importantly, once arthritis was established, PEG-hirudin also showed a curative
      effect. In conclusion, PEG-hirudin can both prevent the onset of CIA in a dose
      dependent manner and ameliorate established arthritis, suggesting that thrombin
      inhibition may offer a new therapeutic approach in arthritis.

PMID- 11238565
TI  - Human C-reactive protein does not bind to FcgammaRIIa on phagocytic cells.

PMID- 11238567
TI  - Modulation of MDR/MRP by wild-type and mutant p53.

PMID- 11238573
TI  - Health Impact Assessment--and beyond.

PMID- 11238569
TI  - Natural killer type 2 bias in remission of multiple sclerosis.
AB  - Multiple sclerosis (MS) is an autoimmune disease characterized by clinical
      relapse and remission. Because of the potential role of natural killer (NK) cells
      in the regulation of autoimmunity, we have examined cytokine profile and surface
      phenotype of NK cells in the peripheral blood of MS. Here we demonstrate that NK
      cells in the remission of MS are characterized by a remarkable elevation of IL-5
      mRNA and a decreased expression of IL-12Rbeta2 mRNA, as well as a higher
      expression of CD95. Moreover, the NK cells from MS in remission produced much
      larger amounts of IL-5 than did those from controls after stimulation with
      phorbol myristate acetate (PMA) and ionomycin. These features are reminiscent of
      those of NK type 2 (NK2) cells that can be induced in a condition favoring
      functional deviation of T cells toward Th2. Remarkably, the NK cells lose the NK2
      like property when relapse of MS occurs, but regain it after recovery. We also
      found that NK2 cells induced in vitro inhibit induction of Th1 cells, suggesting
      that the NK2-like cells in vivo may also prohibit autoimmune effector T cells.
      Taken together, it is possible that NK cells play an active role in maintaining
      the remission of MS.

PMID- 11238574
TI  - Household energy, health and development.

PMID- 11238575
TI  - Glossaries in public health: older people.

PMID- 11238577
TI  - Longitudinal study of associations between perceived health status and self
      reported diseases in the French Gazel cohort.
AB  - STUDY OBJECTIVE: Although perceived health status is an indicator widely used in
      epidemiological studies, its relation to various diseases is not well known. The
      objective of this study is to examine these relations in detail. DESIGN: Marginal
      models used for a longitudinal study of the association between three health
      scales and 47 diseases among 12 164 men and 44 diseases among 4415 women.
      SETTING: French Gazel cohort during the period from 1991 to 1996. MAIN RESULTS:
      The general health status scale was significantly associated with 43 diseases
      among men, and 31 among women. Some of these significantly associated diseases
      were physical (for example, cancer and cerebrovascular accident) and others,
      psychological (for example, depression). The mental fatigue scale was more
      specifically associated with psychological disorders, including sleep problems,
      depression, and nervous diseases. Moreover, modifications in subjects' assessment
      of their health from one year to the next were generally associated with
      modifications in reported diseases. CONCLUSION: Although the mechanism that
      relates the presence of a disease to perceived health status remains in question,
      these results show clearly that there is a close association between these two
      domains that justifies the use of perceived health as a proxy for self reported
      diseases.

PMID- 11238576
TI  - Self rated health and mortality: a long term prospective study in eastern
      Finland.
AB  - STUDY OBJECTIVE: To assess the relation between self rated health and mortality
      over a period of 23 years, taking into account medical history, cardiovascular
      risk factors, and education at the beginning of the follow up. DESIGN: A cohort
      of random population samples. The baseline studies included a self administered
      questionnaire and a health examination. Mortality data were collected from the
      national mortality register using personal identification numbers. SETTING: The
      provinces of North Karelia and Kuopio in eastern Finland. PARTICIPANTS: Random
      samples of working age people (n=21 302) from the population register. MAIN
      RESULTS: For self rated health, the age adjusted poor to good relative risk for
      all cause mortality was 2.36 (95% confidence intervals 2.10, 2.64) for men and
      1.90 (1.63, 2.22) for women, and for cardiovascular mortality 2.29 (1.96, 2.68)
      for men and 2.34 (1.84, 2.96) for women. Adjusted for selected potentially fatal
      diseases from the subjects' medical histories, cardiovascular disease risk
      factors, and education, the corresponding relative risks for all cause mortality
      were 1.66 (1.47, 1.88) for men and 1.50 (1.26, 1.78) for women, and for
      cardiovascular mortality 1.54 (1.29, 1.82) for men and 1.63 (1.26, 2.10) for
      women. The association between self rated health and mortality attributable to
      external causes was fairly strong. CONCLUSIONS: Poor self rated health is a
      strong predictor of mortality, and the association is only partly explained by
      medical history, cardiovascular disease risk factors, and education.

PMID- 11238578
TI  - Material deprivation and leading causes of death by gender: evidence from a
      nationwide small area study.
AB  - STUDY OBJECTIVE: To investigate the association between material deprivation and
      10 leading causes of death by gender. DESIGN: Small area cross sectional
      ecological study using two dimensions of material deprivation (Index 1 and Index
      2) drawn from 1991 census and cause specific mortality data aggregated for 1987
      1995. SETTING: 2218 small areas in Spain. MAIN RESULTS: Strong detrimental
      associations of two deprivation indices were found with top six leading causes of
      death for men and top seven leading causes of death for women, except breast
      cancer. For men, the highest percentages of excess mortality (between 40% and
      60%) were found for smoking and alcohol related causes of death such as lung
      cancer, chronic obstructive pulmonary diseases, and cirrhosis while for women the
      highest percentages of excess mortality (between 40% and 60%) were found for diet
      related causes such as diabetes and ischaemic heart disease. CONCLUSIONS: Health
      inequality is a widespread phenomenon in the majority of the top leading causes
      of deaths of the nation. Increasing levels of deprivation indices are associated
      with mortality risk differently by both cause and gender. Results suggest that
      deprivation effects mainly captured by Index 2 may manifest largely as
      unfavourable health behaviours leading to gender specific sets of causes of
      deaths. Findings of this study are consistent with the idea that material
      deprivation determines health inequality through both an increase of general
      susceptibility to ill health, leading to excess mortality in a wide range of
      causes, and a set of specific factors, resulting in an increased risk of death
      from a specific set of causes in each gender.

PMID- 11238579
TI  - Neighbourhood level and individual level SES effects on child problem behaviour:
      a multilevel analysis.
AB  - OBJECTIVE: This study examined whether neighbourhood level socioeconomic
      variables have an independent effect on reported child behaviour problems over
      and above the effect of individual level measures of socioeconomic status. DESIGN
      AND SETTING: Multilevel analysis of cross sectional survey data relating
      individual level child behavioural problems and parental measures of
      socioeconomic status with neighbourhood level measures of socioeconomic
      deprivation in the city of Maastricht, the Netherlands. PARTICIPANTS: Children
      born in the years 1990-1991 attending the second grade of normal kindergarten
      schools in the city of Maastricht, the Netherlands. Out of 1417 eligible 5-7 year
      olds, the parents of 734 children (51.8%) agreed to participate. MAIN RESULTS:
      Child behaviour problems were more frequent in families of low parental
      occupation and education (F=14.51, df 3, 721, p<0.001; F=12.20, df 3, 721,
      p<0.001, respectively) and in families living in deprived neighbourhoods
      (F=13.26, df 2, 722, p<0.001). Multilevel random effects regression analysis
      showed that the effect of neighbourhood level deprivation remained after
      adjustment for individual level socioeconomic status (B over three levels of
      deprivation: 1.36; 95%CI=0.28, 2.45). CONCLUSIONS: Living in a more deprived
      neighbourhood is associated with higher levels of child problem behaviour,
      irrespective of individual level socioeconomic status. The additional effect of
      the neighbourhood may be attributable to contextual variables such as the level
      of social cohesion among residents.

PMID- 11238580
TI  - Hepatitis A vaccination during an outbreak among gay men in Montreal, Canada,
      1995-1997.
AB  - STUDY OBJECTIVE: To evaluate an intervention designed to curtail an outbreak of
      hepatitis A among gay men, especially the young and sexually active, by promoting
      their free vaccination. DESIGN: The study analysed routine passive surveillance
      data, carried out questionnaire and serological surveys of vaccinees, and surveys
      among the target population in non-clinical venues. SETTING AND INTERVENTION: 15
      000 free doses of hepatitis A vaccine were made available through clinics with
      large gay clienteles, or at gay events, and advertised by various means, in
      Montreal, Canada, from August 1996 to November 1997. Simultaneous vaccination
      against hepatitis B (always free for gay men) was also encouraged. PARTICIPANTS:
      Information was obtained from persons with the disease during the epidemic
      period, a sample of men requesting vaccination, and five community samples of gay
      men. MAIN RESULTS: The outbreak involved 376 gay men and the vaccine was
      distributed to approximately 10 000. Vaccinees were older than cases, but had
      many sex partners and comprised more food handlers. Special vaccination clinics
      at gay events were well attended but did not reach more high risk men than
      regular medical venues. A self reported vaccine coverage of 49% was achieved, but
      26% of vaccinees already had anti-HAV antibodies. Disease incidence declined
      rapidly during the campaign. CONCLUSIONS: The intervention nearly tripled self
      reported hepatitis A vaccine coverage but its late start precludes proving that
      it caused the subsequent drop in incidence. However, it also increased hepatitis
      B vaccination and it is believed it improved links between gay men, public
      health, clinicians and community groups.

PMID- 11238581
TI  - Health promotion research: dilemmas and challenges.
AB  - OBJECTIVE: To analyse dilemmas and challenges in health promotion research, and
      to generate ideas for future development. METHOD: The analysis is based on
      authors' experiences in working in the field of research and action in health
      promotion and on experiences of others as found in literature. RESULTS: The
      assumptions underlying scientific research as based in the biomedical design are
      difficult to meet in community-based health promotion research. Dilemmas are
      identified in relation to the possibility of defining the independent and
      dependent variables beforehand and the intermingling of these variables (the
      intervention and outcome dilemma), the difficulty in quantifying the desired
      outcomes (the number dilemma), and the problem of diffusion of the programme to
      the control group (the control group dilemma). CONCLUSION: Research in health
      promotion has specific reasons to reconsider the approach towards research, the
      selection of outcome variables, and research techniques. Strategies and methods
      to make activities and their outcomes clear are discussed and criteria to judge
      confidence and applicability of research findings are presented.

PMID- 11238582
TI  - An analysis of health levels and various indicators of urban environments for
      Healthy Cities projects.
AB  - STUDY OBJECTIVES: (1) To identify and to categorise the various city indicators
      that are related to health levels; (2) to demonstrate the extent of the influence
      on health of these categorised health determinants; and (3) to demonstrate both
      the interactive associations among the health determinants and the magnitude of
      influence of each health determinant on the people's health. DESIGN: By using
      city statistics of study areas, the health index and health determinant indices
      were formulated. The extent of influence of health determinants on the health
      index was examined by regression analysis; the interrelations between the health
      determinants and the health index were examined by correlation analysis. SETTING:
      All the administrative units in Japan with populations more than 100 000 were
      selected as study areas to analyse the relation of health and health
      determinants. MAIN RESULTS: The nine health determinant indices used-healthcare
      resources, preventive health activities, environmental quality, housing, urban
      clutter, local economy, employment, income, and education-explained 51.6% of the
      variances of the health index as a whole in the cities studies. The health
      determinant indices showed interrelations with each other, in addition to
      individual health determinant indices having a high correlation with the health
      level index of the population. CONCLUSIONS: Both individually and collectively
      the health determinants are closely related to the health status of a population
      and individual determinants interact with each other. Simultaneous analysis of
      the interrelations among health determinants and health status would contribute
      to widen integration oriented perspective in policy interventions based on
      collaboration between different sectors of society.

PMID- 11238583
TI  - Non-communicable disease mortality rates using the verbal autopsy in a cohort of
      middle aged and older populations in Beirut during wartime, 1983-93.
AB  - STUDY OBJECTIVES: Health priorities in middle to low income countries, such as
      Lebanon, have traditionally been assumed to follow those of a "typical"
      developing country, with a focus on the young and on communicable diseases. This
      study was carried out to quantify the magnitude of communicable and non
      communicable disease mortality and to examine mortality pattern among middle aged
      and older populations in an urban setting in Lebanon. DESIGN AND PARTICIPANTS: A
      representative cohort of 1567 men and women (>/=50 years) who had participated in
      a cross sectional multi-dimensional health survey in Beirut, Lebanon in 1983 and
      were followed up 10 years later. Vital status was ascertained and causes of death
      were obtained through verbal autopsy. RESULTS: Total mortality rates were
      estimated at 33.7 and 25.2/1000 person years among men and women respectively. In
      both sexes, the leading causes of death were non-communicable, mainly circulatory
      diseases (60%) and cancer (15%). For all cause mortality, men had significantly
      higher risk than women (age adjusted rate ratio, RR=1.42, 95% confidence
      intervals (CI) = 1.16, 1.72) especially at younger ages. Except for
      cerebrovascular diseases, renal problems and injuries attributable to falls and
      fractures, men were also at higher cause specific mortality risk than women, in
      particular, for ischaemic heart disease (RR = 2.24, 95% CI = 1.62, 3.12).
      Comparison with earlier death certificate data in Lebanon and current estimates
      from other regions in the world showed the magnitude of cardiovascular disease
      over time. CONCLUSIONS: The results from this first cohort study in the Arab
      region show, in contrast with popular perception, a mortality pattern more like a
      developed country than a developing one. Strategies of public health activities,
      in particular for countries in transition, need to be continuously re-assessed in
      light of empirical epidemiological data and other health indicators for evidence
      based decision making.

PMID- 11238585
TI  - Dramatic decline of serogroup C meningococcal disease incidence in Catalonia
      (Spain) 24 months after a mass vaccination programme of children and young
      people.
AB  - STUDY OBJECTIVES: The objective of this study was to evaluate the effectiveness
      of a mass vaccination programme carried out in Catalonia (Spain) in the last
      quarter of 1997 in response to an upsurge of serogroup C meningococcal disease
      (SCMD). DESIGN: Vaccination coverage in the 18 month to 19 years age group was
      investigated by means of a specific vaccination register. Vaccination
      effectiveness was calculated using the prospective cohort method. Cases of SCMD
      were identified on the basis of compulsory reporting and microbiological
      notification by hospital laboratories. Vaccination histories were investigated in
      all cases. Unadjusted and age adjusted vaccination effectiveness referred to the
      time of vaccination and the corresponding 95% confidence intervals (CI) were
      estimated at 6, 12, 18 and 24 months of follow up. SETTING: All population aged
      18 months to 19 years of Catalonia. MAIN RESULTS: A total of seven cases of SCMD
      were detected at six months of follow up (one in the vaccinated cohort), 12 cases
      at 12 months (one in the vaccinated cohort), 19 cases at 18 months (two in the
      vaccinated cohort) and 24 at 24 months (two in the vaccinated cohort). The age
      adjusted effectiveness was 84% (95%CI 30, 97) at six months, 92% (95%CI 63, 98)
      at 12 months, 92% (95% CI 71, 98) at 18 months and 94% (95%CI 78, 98) at 24
      months. In the target population, cases have been reduced by more than two thirds
      (68%) two years after the vaccination programme. In the total population the
      reduction was 43%. CONCLUSION: Vaccination effectiveness has been high in
      Catalonia, with a dramatic reduction in disease incidence in the vaccinated
      cohort accompanied by a relevant reduction in the overall population. Given that
      vaccination coverage was only 54.6%, it may be supposed that this vaccination
      effectiveness is attributable, in part, to the herd immunity conferred by the
      vaccine.

PMID- 11238584
TI  - Evaluation of "Live for Life", a health promotion programme in the County of
      Skaraborg, Sweden.
AB  - STUDY OBJECTIVE: To evaluate a health promotion programme, combining a population
      and individual based strategy, in the County of Skaraborg, Sweden, with special
      attention to outcome. DESIGN: The evaluation was subdivided into structure,
      process and outcome. The evaluation procedure as a total is described here, but
      the results presented refer only to outcome. In order to study the potential
      effect of the individually based health examination, 35 year old subjects who had
      participated five years previously were in 1994-1996 compared with 35 year old
      subjects who had not participated before, and compared with their own values five
      years earlier. The results during 1995-1996 were compared with those of 1989-1990
      for corresponding ages in order to study the effect of, particularly, the
      population based strategy. SETTING: The County of Skaraborg in the south western
      part of Sweden with about 270 000 inhabitants. In addition to population
      strategy, involving the total county, men and women aged 30 and 35 years were
      invited to an individually based examination. MAIN RESULTS: Factors related to
      body weight increased during the study period, while other factors mostly changed
      in the direction wanted. As a whole the changes were rather modest. There were
      favourable changes in lifestyle variables, for example, concerning smoking and
      dietary habits. CONCLUSIONS: There were beneficial effects from the health
      promotion programme, but there is a need for continuous improvement of methods of
      intervention referred to lifestyle.

PMID- 11238586
TI  - Identification of a crucial energetic footprint on the alpha1 helix of human
      histocompatibility leukocyte antigen (HLA)-A2 that provides functional
      interactions for recognition by tax peptide/HLA-A2-specific T cell receptors.
AB  - Structural studies have shown that class I major histocompatibility complex (MHC)
      restricted peptide-specific T cell receptor (TCR)-alpha/betas make multiple
      contacts with the alpha1 and alpha2 helices of the MHC, but it is unclear which
      or how many of these interactions contribute to functional binding. We have
      addressed this question by performing single amino acid mutagenesis of the 15 TCR
      contact sites on the human histocompatibility leukocyte antigen (HLA)-A2 molecule
      recognized by the A6 TCR specific for the Tax peptide presented by HLA-A2. The
      results demonstrate that mutagenesis of only three amino acids (R65, K66, and
      A69) that are clustered on the alpha1 helix affected T cell recognition of the
      Tax/HLA-A2 complex. At least one of these three mutants affected T cell
      recognition by every member of a large panel of Tax/HLA-A2-specific T cell lines.
      Biacore measurements showed that these three HLA-A2 mutations also altered A6 TCR
      binding kinetics, reducing binding affinity. These results show that for Tax/HLA
      A2-specific TCRs, there is a location on the central portion of the alpha1 helix
      that provides interactions crucial to their function with the MHC molecule.

PMID- 11238587
TI  - Lyn is essential for fcgamma receptor III-mediated systemic anaphylaxis but not
      for the Arthus reaction.
AB  - The Src family kinase Lyn initiates intracellular signal transduction by
      associating with a variety of immune receptors such as antigen receptor on B
      cells and high-affinity Fc receptor (FcR) for immunoglobulin Ig(E) (FcepsilonRI)
      on mast cells. Involvement of Lyn in the IgE-mediated immediate-type
      hypersensitivity is well documented, but the physiological significance of Lyn in
      IgG-dependent, type III low-affinity FcR for IgG (FcgammaRIII)-mediated responses
      is largely unknown. In this study, we generated a double-mutant mouse strain
      deficient in both type II FcR for IgG (FcgammaRIIB) and Lyn to exclude any
      involvement of inhibitory signaling by FcgammaRIIB, which otherwise downregulates
      FcgammaRIII-mediated cellular responses. FcgammaRIIB-deficient but Lyn-sufficient
      mice served as controls. The Lyn deficiency attenuated IgG-mediated systemic
      anaphylaxis in vivo, and significantly reduced calcium mobilization and
      degranulation responses of bone marrow-derived mast cells (BMMCs) in vitro.
      However, we found that either interleukin 4 or tumor necrosis factor alpha
      release by BMMCs was comparable to that from Lyn-deficient and control mice, and
      the reverse-passive Arthus reaction was equally induced in both mutant mice,
      indicating that Lyn is not involved in the onset of the IgG-mediated, FcgammaRIII
      dependent late phase responses of mast cells. These findings provide us with
      insight into distinct signaling mechanisms in mast cells underlying the
      development of diverse pathologies as well as a therapeutic potential for
      selective treatment of allergic disorders.

PMID- 11238588
TI  - Aberrant in vivo T helper type 2 cell response and impaired eosinophil
      recruitment in CC chemokine receptor 8 knockout mice.
AB  - Chemokine receptors transduce signals important for the function and trafficking
      of leukocytes. Recently, it has been shown that CC chemokine receptor (CCR)8 is
      selectively expressed by Th2 subsets, but its functional relevance is unclear. To
      address the biological role of CCR8, we generated CCR8 deficient (-/-) mice. Here
      we report defective T helper type 2 (Th2) immune responses in vivo in CCR8(-/)-
      mice in models of Schistosoma mansoni soluble egg antigen (SEA)-induced granuloma
      formation as well as ovalbumin (OVA)- and cockroach antigen (CRA)-induced
      allergic airway inflammation. In these mice, the response to SEA, OVA, and CRA
      showed impaired Th2 cytokine production that was associated with aberrant type 2
      inflammation displaying a 50 to 80% reduction in eosinophils. In contrast, a
      prototypical Th1 immune response, elicited by Mycobacteria bovis purified protein
      derivative (PPD) was unaffected by CCR8 deficiency. Mechanistic analyses
      indicated that Th2 cells developed normally and that the reduction in eosinophil
      recruitment was likely due to systemic reduction in interleukin 5. These results
      indicate an important role for CCR8 in Th2 functional responses in vivo.

PMID- 11238589
TI  - High constitutive glucocorticoid receptor beta in human neutrophils enables them
      to reduce their spontaneous rate of cell death in response to corticosteroids.
AB  - Neutrophils are markedly less sensitive to glucocorticoids than T cells, making
      it difficult to control inflammation in neutrophil-mediated diseases. Development
      of new antiinflammatory strategies for such diseases would be aided by an
      understanding of mechanisms underlying differential steroid responsiveness. Two
      protein isoforms of the human glucocorticoid receptor (GR) exist, GRalpha and
      GRbeta, which arise from alternative splicing of the GR pre-mRNA primary
      transcripts. GRbeta does not bind glucocorticoids and is an inhibitor of GRalpha
      activity. Relative amounts of these two GRs can therefore determine the level of
      glucocorticoid sensitivity. In this study, human neutrophils and peripheral blood
      mononuclear cells (PBMCs) were studied to determine the relative amounts of each
      GR isoform. The mean fluorescence intensity (MFI) using immunofluorescence
      analysis for GRalpha was 475 +/- 62 and 985 +/- 107 for PBMCs and neutrophils,
      respectively. For GRbeta, the MFI was 350 +/- 60 and 1,389 +/- 143 for PBMCs and
      neutrophils, respectively (P < 0.05). After interleukin (IL)-8 stimulation of
      neutrophils, there was a statistically significant increase in intensity of
      GRbeta staining to 2,497 +/- 140 (P < 0.05). No change in GRalpha expression was
      observed. This inversion of the GRalpha/GRbeta ratio in human neutrophils
      compared with PBMCs was confirmed by quantitative Western analysis. Increased
      GRbeta mRNA expression in neutrophils at baseline, and after IL-8 exposure, was
      observed using RNA dot blot analysis. Increased levels of GRalpha/GRbeta
      heterodimers were found in neutrophils as compared with PBMCs using
      coimmunoprecipitation/Western analysis. Transfection of mouse neutrophils, which
      do not contain GRbeta, resulted in a significant reduction in the rate of cell
      death when treated with dexamethasone.We conclude that high constitutive
      expression of GRbeta by human neutrophils may provide a mechanism by which these
      cells escape glucocorticoid-induced cell death. Moreover, upregulation of this GR
      by proinflammatory cytokines such as IL-8 further enhances their survival in the
      presence of glucocorticoids during inflammation.

PMID- 11238590
TI  - Antiviral CD8+ T cell responses in neonatal mice: susceptibility to polyoma virus
      induced tumors is associated with lack of cytotoxic function by viral antigen
      specific T cells.
AB  - Polyoma virus is a potent oncogenic pathogen when inoculated into newborn mice of
      particular H-2(k) strains. Using D(k) tetramers containing the dominant
      antipolyoma CD8(+) T cell epitope, middle T protein (MT)389-397, and
      intracellular interferon gamma staining, we enumerated MT389-specific CD8(+) T
      cells in infected neonates having opposite susceptibilities to polyoma virus
      induced tumors. In resistant mice, MT389-specific CD8(+) T cells dramatically
      expanded during acute infection in neonates to a frequency rivaling that in
      adults; furthermore, in both neonatal and adult mice, this antipolyoma CD8(+) T
      cell response exhibited nearly identical T cell receptor (TCR) functional
      avidities and TCR functional fingerprints. Susceptible mice mounted an MT389
      specific CD8(+) T cell response of only fourfold lower magnitude than resistant
      mice; but, in clear contrast to resistant mice, these CD8(+) T cells lacked ex
      vivo MT389-specific cytotoxic activity. However, MT389-specific CD8(+) T cells in
      resistant and susceptible mice expressed similar TCR avidities, perforin levels,
      and surface type O-glycan levels indicative of mature CD8(+) T cell effectors.
      Upon in vitro restimulation with infected antigen-presenting cells, CD8(+) T
      cells from acutely infected susceptible neonates acquired strong MT389-specific
      cytotoxicity. These findings indicate that polyoma-specific CD8(+) T cells are
      armed with, but restrained from deploying, their cytotoxic effector function in
      mice susceptible to polyoma virus tumorigenesis.

PMID- 11238592
TI  - Molecular basis for hematopoietic/mesenchymal interaction during initiation of
      Peyer's patch organogenesis.
AB  - Mice deficient in lymphotoxin beta receptor (LTbetaR) or interleukin 7 receptor
      alpha (IL-7Ralpha) lack Peyer's patches (PPs). Deficiency in CXC chemokine
      receptor 5 (CXCR5) also severely affects the development of PPs. A molecular
      network involving these three signaling pathways has been implicated in PP
      organogenesis, but it remains unclear how they are connected during this process.
      We have shown that PP organogenesis is initiated at sites containing IL
      7Ralpha(+) lymphoid cells and vascular cell adhesion molecule (VCAM)
      1/intercellular adhesion molecule (ICAM)-1 expressing nonlymphoid elements. Here
      we characterize these lymphoid and nonlymphoid components in terms of chemokine
      signals. The lymphoid population expresses CXCR5 and has a strong chemotactic
      response to B lymphocyte chemoattractant (BLC). Importantly, chemokines produced
      by VCAM-1(+)ICAM-1(+) nonlymphoid cells mediate the recruitment of lymphoid
      cells. Furthermore, we show that these VCAM-1(+)ICAM-1(+) cells are mesenchymal
      cells that are activated by lymphoid cells through the LTbetaR to express
      adhesion molecules and chemokines. Thus, promotion of PP development relies on
      mutual interaction between mesenchymal and lymphoid cells.

PMID- 11238591
TI  - Selective inhibition of vascular endothelial growth factor-mediated angiogenesis
      by cyclosporin A: roles of the nuclear factor of activated T cells and
      cyclooxygenase 2.
AB  - Cyclosporin A (CsA) is an immunosuppressive drug that inhibits the activity of
      transcription factors of the nuclear factor of activated T cells (NFAT) family,
      interfering with the induction of cytokines and other inducible genes required
      for the immune response. Here we show that CsA inhibits migration of primary
      endothelial cells and angiogenesis induced by vascular endothelial growth factor
      (VEGF); this effect appears to be mediated through the inhibition of
      cyclooxygenase (Cox)-2, the transcription of which is activated by VEGF in
      primary endothelial cells. Consistent with this, we show that the induction of
      Cox-2 gene expression by VEGF requires NFAT activation. Most important, the CsA
      mediated inhibition of angiogenesis both in vitro and in vivo was comparable to
      the Cox-2 inhibitor NS-398, and reversed by prostaglandin E(2). Furthermore, the
      in vivo corneal angiogenesis induced by VEGF, but not by basic fibroblast growth
      factor, was selectively inhibited in mice treated with CsA systemically. These
      findings involve NFAT in the regulation of Cox-2 in endothelial cells, point to a
      role for this transcription factor in angiogenesis, and may provide a novel
      mechanism underlying the beneficial effects of CsA in angiogenesis-related
      diseases such as rheumatoid arthritis and psoriasis.

PMID- 11238593
TI  - Essential role of nuclear factor (NF)-kappaB-inducing kinase and inhibitor of
      kappaB (IkappaB) kinase alpha in NF-kappaB activation through lymphotoxin beta
      receptor, but not through tumor necrosis factor receptor I.
AB  - Both nuclear factor (NF)-kappaB-inducing kinase (NIK) and inhibitor of kappaB
      (IkappaB) kinase (IKK) have been implicated as essential components for NF-kappaB
      activation in response to many external stimuli. However, the exact roles of NIK
      and IKKalpha in cytokine signaling still remain controversial. With the use of in
      vivo mouse models, rather than with enforced gene-expression systems, we have
      investigated the role of NIK and IKKalpha in signaling through the type I tumor
      necrosis factor (TNF) receptor (TNFR-I) and the lymphotoxin beta receptor
      (LTbetaR), a receptor essential for lymphoid organogenesis. TNF stimulation
      induced similar levels of phosphorylation and degradation of IkappaBalpha in
      embryonic fibroblasts from either wild-type or NIK-mutant mice. In contrast,
      LTbetaR stimulation induced NF-kappaB activation in wild-type mice, but the
      response was impaired in embryonic fibroblasts from NIK-mutant and IKKalpha
      deficient mice. Consistent with the essential role of IKKalpha in LTbetaR
      signaling, we found that development of Peyer's patches was defective in IKKalpha
      deficient mice. These results demonstrate that both NIK and IKKalpha are
      essential for the induction of NF-kappaB through LTbetaR, whereas the NIK
      IKKalpha pathway is dispensable in TNFR-I signaling.

PMID- 11238594
TI  - Independence of herpesvirus-induced T cell lymphoma from viral cyclin D
      homologue.
AB  - Cyclin D family members are cellular protooncogenes, and their viral homologues
      in the Kaposi's sarcoma-associated herpesvirus (KSHV, human herpesvirus type 8
      [HHV-8]) and the closely related Herpesvirus saimiri have been implicated as
      putative cofactors of viral transformation and pathogenesis. KSHV is regularly
      found in Kaposi's sarcoma and in the primary effusion B cell lymphoma and
      Castleman's disease associated with immunosuppression and AIDS. H. saimiri strain
      C488 transforms human and marmoset T cells in vitro and causes polyclonal T cell
      lymphoma in New World monkeys. The viral cyclins stimulate cell cycle progression
      of quiescent fibroblasts, and they form active cyclin-dependent kinase (CDK)6
      complexes of broad substrate specificity that can resist and downregulate
      cellular CDK inhibitors. This study shows that the viral cyclin of H. saimiri
      strain C488 is not required for viral replication, T cell transformation, and
      pathogenicity in New World primates.

PMID- 11238595
TI  - An instructive component in T helper cell type 2 (Th2) development mediated by
      GATA-3.
AB  - Although interleukin (IL)-12 and IL-4 polarize naive CD4(+) T cells toward T
      helper cell type 1 (Th1) or Th2 phenotypes, it is not known whether cytokines
      instruct the developmental fate in uncommitted progenitors or select for
      outgrowth of cells that have stochastically committed to a particular fate. To
      distinguish these instructive and selective models, we used surface affinity
      matrix technology to isolate committed progenitors based on cytokine secretion
      phenotype and developed retroviral-based tagging approaches to directly monitor
      individual progenitor fate decisions at the clonal and population levels. We
      observe IL-4-dependent redirection of phenotype in cells that have already
      committed to a non-IL-4-producing fate, inconsistent with predictions of the
      selective model. Further, retroviral tagging of naive progenitors with the Th2
      specific transcription factor GATA-3 provided direct evidence for instructive
      differentiation, and no evidence for the selective outgrowth of cells committed
      to either the Th1 or Th2 fate. These data would seem to exclude selection as an
      exclusive mechanism in Th1/Th2 differentiation, and support an instructive model
      of cytokine-driven transcriptional programming of cell fate decisions.

PMID- 11238597
TI  - Assessing CD8 T cell number and dysfunction in the presence of antigen.

PMID- 11238598
TI  - In memoriam. Elvin Abraham Kabat, September 1, 1914-June 16, 2000.

PMID- 11238596
TI  - Critical contribution of tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL) to apoptosis of human CD4+ T cells in HIV-1-infected hu-PBL-NOD-SCID
      mice.
AB  - Apoptosis is a key for CD4+ T cell destruction in HIV-1-infected patients. In
      this study, human peripheral blood lymphocyte (PBL)-transplanted nonobese
      diabetic (NOD)-severe combined immunodeficient (SCID) (hu-PBL-NOD-SCID) mice were
      used to examine in vivo apoptosis after HIV-1 infection. As the hu-PBL-NOD-SCID
      mouse model allowed us to see extensive infection with HIV-1 and to analyze
      apoptosis in human cells in combination with immunohistological methods, we were
      able to quantify the number of apoptotic cells with HIV-1 infection. As
      demonstrated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end
      labeling (TUNEL), massive apoptosis was predominantly observed in virus
      uninfected CD4+ T cells in the spleens of HIV-1-infected mice. A combination of
      TUNEL and immunostaining for death-inducing tumor necrosis factor (TNF) family
      molecules indicated that the apoptotic cells were frequently found in conjugation
      with TNF-related apoptosis-inducing ligand (TRAIL)-expressing CD3+CD4+ human T
      cells. Administration of a neutralizing anti-TRAIL mAb in HIV-1-infected mice
      markedly inhibited the development of CD4+ T cell apoptosis. These results
      suggest that a large number of HIV-1-uninfected CD4+ T cells undergo TRAIL
      mediated apoptosis in HIV-infected lymphoid organs.

PMID- 11238599
TI  - Cutting edge: CD43 functions as a T cell counterreceptor for the macrophage
      adhesion receptor sialoadhesin (Siglec-1).
AB  - Sialoadhesin (Siglec-1) is a macrophage-restricted sialic acid-binding receptor
      that mediates interactions with hemopoietic cells, including lymphocytes. In this
      study, we identify sialoadhesin counterreceptors on T lymphocytes. Several major
      glycoproteins (85, 130, 240 kDa) were precipitated by sialoadhesin-Fc fusion
      proteins from a murine T cell line (TK-1). Binding of sialoadhesin to these
      glycoproteins was sialic acid dependent and was abolished by mutation of a
      critical residue (R97A) of the sialic acid binding site in the membrane distal Ig
      like domain of sialoadhesin. The 130- and 240-kDa sialoadhesin-binding
      glycoproteins were identified as the sialomucins CD43 and P-selectin glycoprotein
      ligand 1 (CD162), respectively. CD43 expressed in COS cells supported increased
      binding to immobilized sialoadhesin. Finally, sialoadhesin bound different
      glycoforms of CD43 expressed in Chinese hamster ovary cells, including unbranched
      (core 1) and branched (core 2) O:-linked glycans, that are normally found on CD43
      in resting and activated T cells, respectively. These results identify CD43 as a
      T cell counterreceptor for sialoadhesin and suggest that in addition to its anti
      adhesive role CD43 may promote cell-cell interactions.

PMID- 11238600
TI  - Cutting edge: regulation of uterine NKT cells by a fetal class I molecule other
      than CD1.
AB  - The peri-implantation uterus contains an expanded population of NK1.1(+) V alpha
      14(+) TCR(int) (NKT) lymphocytes. Although these cells bear the above features in
      common with other NKT cells populations in thymus, bone marrow, liver, and
      spleen, they differ from these other populations in terms of an altered V beta
      repertoire and absence of a CD4(+) component. In this study, we demonstrate that
      the uterine population also differs from other NKT cell populations because they
      recognize a class I/class I-like molecule other than CD1, whereas most previously
      described V alpha 14(+) NKT cells are CD1-restricted. Moreover, the class I/class
      I-like molecule leading to the uterine NKT cell expansion may be supplied by the
      fetus. These data demonstrate a novel mechanism whereby the fetus is capable of
      modulating the maternal immune system.

PMID- 11238601
TI  - Cutting edge: CTLs rapidly capture membrane fragments from target cells in a TCR
      signaling-dependent manner.
AB  - Upon encounter of a CTL with a target cell carrying foreign Ags, the TCR
      internalizes with its ligand, the peptide-MHC class I complex. However, it is
      unclear how this can happen mechanistically because MHC molecules are anchored to
      the target cell's surface via a transmembrane domain. By using antigenic peptides
      and lipids that were fluorescently labeled, we found that CTLs promptly capture
      target cell membranes together with the antigenic peptide as well as various
      other surface proteins. This efficient and specific capture process requires
      sustained TCR signaling. Our observations indicate that this process allows
      efficient acquisition of the Ag by CTL, which may in turn regulate lymphocyte
      activation or elimination.

PMID- 11238602
TI  - Cutting edge: nociceptin stimulates neutrophil chemotaxis and recruitment:
      inhibition by aspirin-triggered-15-epi-lipoxin A4.
AB  - The nociceptin receptor (Noci-R) is a G protein-coupled receptor present in
      neural tissues and its activation by nociceptin is involved in the processing of
      pain signals. Here, we report that Noci-R is present and functional on peripheral
      blood polymorphonuclear leukocytes (PMN). Human PMN express mRNA for Noci-R, its
      nucleotide sequence determined, and specific binding with [(125)I]-labeled
      nociceptin gave an apparent K(d) approximately 1.5 nM for this PMN opioid
      receptor. Nociceptin evoked PMN chemotaxis with maximal activity at 100 pM,
      without intracellular Ca(2+) mobilization. When injected in murine air pouches,
      nociceptin elicited leukocyte infiltration in a concentration-dependent fashion.
      Nociceptin-stimulated PMN infiltration was inhibited by treating mice with a
      synthetic analog of the aspirin-triggered lipid mediator 15-epi-lipoxin A(4). The
      present results identify nociceptin as a potent chemoattractant and provide a
      novel link between the neural and immune systems that are blocked by aspirin
      triggered lipid mediators and may be relevant in neurogenic inflammation.

PMID- 11238603
TI  - Cutting edge: human gamma delta T cells are activated by intermediates of the 2-C
      methyl-D-erythritol 4-phosphate pathway of isoprenoid biosynthesis.
AB  - Activation of V gamma 9/V delta 2 T cells by small nonprotein Ags is frequently
      observed after infection with various viruses, bacteria, and eukaryotic
      parasites. We suggested earlier that compounds synthesized by the 2-C:-methyl-D
      erythritol 4-phosphate (MEP) pathway of isopentenyl pyrophosphate synthesis are
      responsible for the V gamma 9/V delta 2 T cell reactivity of many pathogens.
      Using genetically engineered Escherichia coli knockout strains, we now
      demonstrate that the ability of E. coli extracts to stimulate gamma delta T cell
      proliferation is abrogated when genes coding for essential enzymes of the MEP
      pathway, dxr or gcpE, are disrupted or deleted from the bacterial genome.

PMID- 11238604
TI  - Cutting edge: critical role of inducible costimulator in germinal center
      reactions.
AB  - Inducible costimulator (ICOS) is a new member of the CD28/CTLA-4 family that is
      expressed on activated and germinal center (GC) T cells. Recently, we reported
      that ICOS-deficient mice exhibited profound defects in T cell activation and
      effector function. Ab responses in a T-dependent primary reaction and in a murine
      asthma model were also diminished. In the current study, we investigate the
      mechanism by which ICOS regulates humoral immunity and examine B cell GC
      reactions in the absence of ICOS. We found that ICOS(-/-) mice, when immunized
      with SRBC, had smaller GCs. Furthermore, IgG1 class switching in the GCs was
      impaired. Remarkably, GC formation in response to a secondary recall challenge
      was completely absent in ICOS knockout mice. These data establish a critical role
      of ICOS in regulation of humoral immunity.

PMID- 11238605
TI  - Testing time-, ignorance-, and danger-based models of tolerance.
AB  - In this study, we present data showing that tolerance to Ags in the periphery is
      not determined by the time at which the Ag appears, or by special properties of
      tissues in newborn mice or newly developing immune systems. We placed male grafts
      onto immunoincompetent female mice, allowed the grafts to heal for up to 5 mo,
      and then repopulated the recipients with fetal liver stem cells. We found that
      the newly arising T cells were neither tolerant nor ignorant of the grafts, but
      promptly rejected them, though they did not reject female grafts, nor show any
      signs of autoimmunity. We also found that the H-Y Ag was continuously cross
      presented on host APCs, that this presentation was immunogenic, not tolerogenic,
      and that it depended on the continuous presence of the graft. In searching for
      the stimulus that might activate the host APCs, we analyzed mRNA expression with
      a highly sensitive real-time quantitative PCR assay. By using two different
      "housekeeping" molecules for comparison, we analyzed the message levels for
      several stress and/or inflammatory molecules in the healed grafts. We found that
      the long-healed grafts were not equivalent to "normal" skin because the healed
      grafts expressed lower levels of GAPDH. Altogether, these data suggest that
      acceptance vs rejection of peripheral tissues is not attributable to ignorance,
      timing-based tolerance, or special circulation properties of naive T cells in
      neonatal tissues. It is more likely attributable to an aspect of the context of
      Ag presentation that remains to be identified.

PMID- 11238606
TI  - Functional caspase-1 is required for Langerhans cell migration and optimal
      contact sensitization in mice.
AB  - Langerhans cell (LC) migration from epidermis to draining lymph node is a
      critical first step in cutaneous immune responses. Both TNF-alpha and IL-1 beta
      are important signals governing this process, but the potential regulatory role
      of IL-1 alpha processing by caspase-1 is unknown. In wild-type (WT) mice,
      application of the contact allergens 2,4-dinitrofluorobenzine and oxazolone lead
      to a marked reduction in epidermal LC numbers, but in caspase-1-deficient mice
      this reduction was not observed. Moreover, although intradermal injection of TNF
      alpha (50 ng) induced epidermal LC migration in WT mice, this cytokine failed to
      induce LC migration in caspase-1-deficient mice. Intradermal IL-1 beta (50 ng)
      caused a similar reduction in epidermal LC numbers in both WT and caspase-1
      deficient mice, indicating that, given an appropriate signal, caspase-1-deficient
      epidermal LC are capable of migration. Contact hypersensitivity to both 2,4
      dinitrofluorobenzine and oxazolone was inhibited in caspase-1-deficient mice,
      indicating a functional consequence of the LC migration defect. In organ culture
      the caspase-1 inhibitor Ac-YVAD-cmk, but not control peptide, potently inhibited
      the epidermal LC migration that occurs in this system, and reduced spontaneous
      migration of LC was observed in skin derived from caspase-1-deficient mice.
      Moreover, Ac-YVAD-cmk applied to BALB/c mouse skin before application of contact
      sensitizers inhibited LC migration and contact hypersensitivity in vivo. Taken
      together, these data indicate that caspase-1 may play a central role in the
      regulation of LC migration and suggest that the activity of this enzyme is
      amenable to control by specific inhibitors both in vivo and in vitro.

PMID- 11238607
TI  - Rapid peptide turnover and inefficient presentation of exogenous antigen
      critically limit the activation of self-reactive CTL by dendritic cells.
AB  - This study evaluated to what extent presentation of exogenously acquired self-Ags
      via MHC class I molecules on DC might contribute to the activation of self
      reactive CTL and subsequent development of autoimmune disease. We show here by
      using the rat insulin promotor lymphocytic choriomeningitis virus glycoprotein
      model of autoimmune diabetes that the activation of self-reactive CTL by DC after
      uptake of exogenous Ag is very limited, first by the short half-life of MHC class
      I-associated peptides on DC in vitro and in vivo, and second by the rather
      inefficient MHC class I presentation of cell-associated self-Ags by DC. These two
      mechanisms are probably crucial in establishing high thresholds for the induction
      of self-reactive CTL that prevent autoimmune sequelae after release of
      sequestered and previously immunologically ignored tissue Ags.

PMID- 11238608
TI  - A mucosal IgA-mediated excretory immune system in vivo.
AB  - The capacity of mucosal IgA Abs to serve as an excretory immune system in vivo
      was investigated. Mice expressing a transgenic TCR were immunized
      intragastrically with the cognate Ag to elicit a vigorous mucosal IgA Ab
      response. Soon after i.v. challenge, Ag was detected within the epithelial cells
      of the small intestinal crypts and to a lesser degree within the epithelial cells
      higher up the villi, paralleling the gradient in expression of the polymeric Ig
      receptor and the transport of its ligand, oligomeric IgA. Uptake of Ag into the
      epithelial cells occurred only from the basolateral aspect and only when Ag
      complexed to IgA Ab could be present in the lamina propria. The results support
      the concept that local IgA Abs can excrete Ags from the body by transporting them
      directly through mucosal epithelial cells, using the same mechanism that
      transports free IgA into the mucosal secretions.

PMID- 11238609
TI  - Translocation of the B cell antigen receptor into lipid rafts reveals a novel
      step in signaling.
AB  - The cross-linking of the B cell Ag receptor (BCR) leads to the initiation of a
      signal transduction cascade in which the earliest events involve the
      phosphorylation of the immunoreceptor tyrosine-based activation motifs of Ig
      alpha and Ig beta by the Src family kinase Lyn and association of the BCR with
      the actin cytoskeleton. However, the mechanism by which BCR cross-linking
      initiates the cascade remains obscure. In this study, using various A20
      transfected cell lines, biochemical and genetic evidence is provided that BCR
      cross-linking leads to the translocation of the BCR into cholesterol- and
      sphingolipid-rich lipid rafts in a process that is independent of the initiation
      of BCR signaling and does not require the actin cytoskeleton. Translocation of
      the BCR into lipid rafts did not require the Ig alpha/Ig beta signaling complex,
      was not dependent on engagement of the FcR, and was not blocked by the Src family
      kinase inhibitor PP2 or the actin-depolymerizing agents cytochalasin D or
      latrunculin. Thus, cross-linking or oligomerization of the BCR induces the BCR
      translocation into lipid rafts, defining an event in B cell activation that
      precedes receptor phosphorylation and association with the actin cytoskeleton.

PMID- 11238610
TI  - Compartmentalization of Peyer's patch anlagen before lymphocyte entry.
AB  - We have shown that Peyer's patch (PP) first develops as a simple and even cell
      aggregation during embryogenesis. To investigate when and how such a simple cell
      aggregation forms the complex PP architecture, we analyzed the distribution of
      cells expressing IL-7R alpha (PP inducer cells), VCAM-1 (mesenchymal cells),
      CD11c (dendritic cells), and mature lymphocytes by whole-mount immunostaining of
      17.5 days post coitus to 2 days postpartum mouse gut. Our results show that
      compartmentalization of PP anlagen commences at day 18.5 of gestation by
      clustering and subsequent follicle formation of IL-7R alpha(+), VCAM-1(+), and
      CD11c(+) cells. This process adds the primitive architecture of PP anlage with
      several follicles in which IL-7R alpha(+) cells localize in the center, while
      VCAM-1(+) and CD11c(+) cells localize at the fringe. This follicle formation is
      accompanied by the establishment of PP-specific vascular network expressing
      mucosal addressin cellular adhesion molecule-1. Mature B and T lymphocytes
      entering in the PP anlage are distributed promptly to their own target zones; B
      cells to the follicle and T cells to nonfollicular zones. Our analysis of
      scid/scid mouse indicate that the initial processes including formation of PP
      specific vascular network occur in the absence of lymphocytes. These observations
      indicate that the basic architecture of PP is formed by a set of cell lineages
      assembled during the initial phase of induction of PP anlagen before entry of
      mature lymphocytes.

PMID- 11238611
TI  - Novel roles for Lyn in B cell migration and lipopolysaccharide responsiveness
      revealed using anti-double-stranded DNA Ig transgenic mice.
AB  - Lyn-deficient mice produce Abs against dsDNA, yet exhibit exaggerated tolerance
      to the model Ag hen-egg lysozyme. To investigate this apparent contradiction, and
      to further examine the function of Lyn in Ag-engaged cells, we have used an anti
      dsDNA Ig transgenic model. Previously, looking at these anti-dsDNA B cells in Lyn
      sufficient BALB/c mice, we showed that they are regulated by functional
      inactivation (anergy). In the absence of Lyn, these anti-dsDNA B cells remain
      unable to secrete Ab. This suggests that functional inactivation of anti-dsDNA B
      cells does not depend on Lyn, and that the anti-dsDNA Abs that are produced in
      lyn(-/-) mice arise from a defect in another mechanism of B cell tolerance.
      Although the anti-dsDNA B cells remain anergic, Lyn deficiency does restore their
      ability to proliferate to LPS. This reveals a novel role for Lyn in mediating the
      LPS unresponsiveness that normally follows surface Ig engagement. Furthermore,
      Lyn deficiency leads to an altered splenic localization and EBV-induced molecule
      1 ligand chemokine responsiveness of anti-dsDNA B cells, as well as an absence of
      marginal zone B cells, suggesting additional roles for Lyn in controlling the
      migration and development of specific B cell populations.

PMID- 11238612
TI  - Dendritic cells acquire antigens from live cells for cross-presentation to CTL.
AB  - Dendritic cells (DC) can readily capture Ag from dead and dying cells for
      presentation to MHC class I-restricted CTL. We now show by using a primate model
      that DC also acquire Ag from healthy cells, including other DC. Coculture assays
      showed that fluorescently labeled plasma membrane was rapidly and efficiently
      transferred between DC, and transfer of intracellular proteins was observed to a
      lesser extent. Acquisition of labeled plasma membrane and intracellular protein
      was cell contact-dependent and was primarily a function of immature DC, whereas
      both immature and CD40L-matured DC could serve as donors. Moreover, immature DC
      could acquire labeled plasma membrane and intracellular proteins from a wide
      range of hemopoietic cells, including macrophages, B cells, and activated T
      cells. Notably, macrophages, which readily phagocytose apoptotic bodies, were
      very inefficient at acquiring labeled plasma membrane and intracellular proteins
      from other live macrophages or DC. With live-cell imaging techniques, we
      demonstrate that individual DC physically extract plasma membrane from other DC,
      generating endocytic vesicles of up to 1 microm in diameter. Finally, DC but not
      macrophages acquired an endogenous melanoma Ag expressed by live DC and cross
      presented Ag to MHC class I-restricted CTL, demonstrating the immunological
      relevance of our finding. These data show for the first time that DC readily
      acquire Ag from other live cells. We suggest that Ag acquisition from live cells
      may provide a novel mechanism whereby DC can present Ag in the absence of direct
      infection, and may serve to expand and regulate the immune response in vivo.

PMID- 11238613
TI  - Concomitant inhibition of Janus kinase 3 and calcineurin-dependent signaling
      pathways synergistically prolongs the survival of rat heart allografts.
AB  - The cytoplasmic localized Janus tyrosine kinase 3 (Jak3) is activated by multiple
      cytokines, including IL-2, IL-4, and IL-7, through engagement of the IL-2R common
      gamma-chain. Genetic inactivation of Jak3 is manifested as SCID in humans and
      mice. These findings have suggested that Jak3 represents a pharmacological target
      to control certain lymphoid-derived diseases. Using the rat T cell line Nb2-11c,
      we document that tyrphostin AG-490 blocked in vitro IL-2-induced cell
      proliferation (IC(50) approximately 20 microM), Jak3 autophosphorylation, and
      activation of its key substrates, Stat5a and Stat5b, as measured by
      tyrosine/serine phosphorylation analysis and DNA-binding experiments. To test the
      notion that inhibition of Jak3 provides immunosuppressive potential, a 7-day
      course of i.v. therapy with 5-20 mg/kg AG-490 was used to inhibit rejection of
      heterotopically transplanted Lewis (RT1(l)) heart allografts in ACI (RT1(a))
      recipients. In this study, we report that AG-490 significantly prolonged
      allograft survival, but also acted synergistically when used in combination with
      the signal 1 inhibitor cyclosporin A, but not the signal 3 inhibitor, rapamycin.
      Finally, AG-490 treatment reduced graft infiltration of mononuclear cells and
      Stat5a/b DNA binding of ex vivo IL-2-stimulated graft infiltrating of mononuclear
      cells, but failed to affect IL2R alpha expression, as judged by RNase protection
      assays. Thus, inhibition of Jak3 prolongs allograft survival and also potentiates
      the immunosuppressive effects of cyclosporin A, but not rapamycin.

PMID- 11238615
TI  - Oligodeoxynucleotides containing CpG motifs induce low levels of TNF-alpha in
      human B lymphocytes: possible adjuvants for Th1 responses.
AB  - Oligodeoxynucleotides containing CpG motifs (CpG-ODN) represent potential
      adjuvants for specific immunotherapy of type I allergies because they foster Th1
      like immune responses. However, previous work has shown that CpG-ODN induce
      systemically active levels of TNF-alpha in murine macrophages. The goal of the
      present study was to evaluate the release of TNF-alpha in human cells by a CpG
      ODN proven to induce Th1 immune responses in cells from atopic individuals and in
      mice. CpG-ODN induced TNF-alpha in cells from atopic and healthy individuals.
      However, the amounts were low, as determined by comparison with commonly used
      Ags. Intracellular cytokine staining of PBMC revealed that CpG-ODN-induced TNF
      alpha derived exclusively from B lymphocytes. TNF-alpha contributed to the CpG
      ODN-augmented proliferation and Ig synthesis in PBMC, but was not involved in IFN
      gamma synthesis. In conclusion, our findings indicate that certain CpG-ODN induce
      low amounts of TNF-alpha in human B lymphocytes and may therefore be used to
      modulate Th2-biased immune responses in allergic patients.

PMID- 11238614
TI  - Normal cellular prion protein is preferentially expressed on subpopulations of
      murine hemopoietic cells.
AB  - We studied the expression of normal cellular prion protein (PrP(C)) in mouse
      lymphoid tissues with newly developed mAbs to PrP(C). Most of the mature T and B
      cells in the peripheral lymphoid organs do not express PrP(C). In contrast, most
      thymocytes are PrP(C+). In the bone marrow, erythroid cells and maturing
      granulocytes are PrP(C+). Approximately 50% of the cells in the region of small
      lymphocytes and progenitor cells also express PrP(C). Most of these PrP(C+) cells
      are CD43(+), but B220(-), surface IgM(-) (sIgM(-)), and IL-7R(-), a phenotype
      that belongs to cells not yet committed to the B cell lineage. Another small
      group of the PrP(C+) cell are B220(+), and some of these are also sIgM(+). The
      majority of the B220(+) cells, however, are PrP(C-). Therefore, PrP(C) is
      preferentially expressed in early bone marrow progenitor cells and subsets of
      maturing B cells. Supporting this interpretation is our observation that
      stimulation of bone marrow cells in vitro with PMA results in a decrease in the
      number of PrP(C+)B220(-) cells with a corresponding increase of sIgM(+)B220(high)
      mature B cells. This result suggests that the PrP(C+)B220(-) cells are potential
      progenitors. Furthermore, in the bone marrow of Rag-1(-/-) mice, there are an
      increased number of PrP(C+)B220(-) cells, and most of the developmentally
      arrested pro-B cells in these mice are PrP(C+). Collectively, these results
      suggest that PrP(C) is expressed preferentially in immature T cells in the thymus
      and early progenitor cells in the bone marrow, and the expression of PrP(C) is
      regulated during hemopoietic differentiation.

PMID- 11238617
TI  - Lymphocytes from autoimmune MRL lpr/lpr mice are hyperresponsive to IL-18 and
      overexpress the IL-18 receptor accessory chain.
AB  - MRL lpr/lpr mice spontaneously develop a severe autoimmune lupus syndrome
      characterized by strong autoantibody production and massive lymphoproliferation,
      in which IFN-gamma plays a major pathogenic effect. The role of the IFN-gamma
      inducing cytokine IL-18 in the autoimmune syndrome of lpr/lpr mice has been
      investigated. In response to IL-18, lymph node cells of lpr/lpr mice produce
      significant amounts of IFN-gamma and proliferate more potently as compared with
      cells from +/+ mice. Cells likely responsible for such hyperresponsiveness to IL
      18 include NK cells and the CD4(+)/CD8(+) self-reactive T lymphocytes
      characteristically present in lymph nodes of lpr/lpr mice. Analysis of the
      expression of IL-18R complex revealed that mRNA for the IL-18R alpha-chain is
      constitutively expressed at similar level both in +/+ and lpr/lpr lymphocytes. In
      contrast, the expression of the accessory receptor chain IL-18R beta is low in
      unstimulated +/+ cells but significantly high in lpr/lpr cells. Thus, the
      abnormally high expression of the IL-18R chain IL-18R beta could be one of the
      causes of the hyperresponsiveness of lpr/lpr cells to IL-18 at the basis of
      consequent enhancement of IFN-gamma production and development of IFN-gamma
      dependent autoimmune pathology.

PMID- 11238616
TI  - NK T cell-induced protection against diabetes in V alpha 14-J alpha 281
      transgenic nonobese diabetic mice is associated with a Th2 shift circumscribed
      regionally to the islets and functionally to islet autoantigen.
AB  - The onset of autoimmune diabetes is related to defective immune regulation.
      Recent studies have shown that NK T cells are deficient in number and function in
      both diabetic patients and nonobese diabetic (NOD) mice. NK T cells, which are
      CD1d restricted, express a TCR with an invariant V alpha 14-J alpha 281 chain and
      rapidly produce large amounts of cytokines. V alpha 14-J alpha 281 transgenic NOD
      mice have increased numbers of NK T cells and are protected against diabetes
      onset. In this study we analyzed where and how NK T cells interfere with the
      development of the anti-islet autoimmune response. NK T cells, which are usually
      rare in lymph nodes, are abundant in pancreatic lymph nodes and are also present
      in islets. IL-4 mRNA levels are increased and IFN-gamma mRNA levels decreased in
      islets from diabetes-free V alpha 14-J alpha 281 transgenic NOD mice; the
      IgG1/IgG2c ratio of autoantibodies against glutamic acid decarboxylase is also
      increased in these mice. Treatment with IL-12 (a pro-Th1 cytokine) or anti-IL-4
      Ab abolishes the diabetes protection in V alpha 14-J alpha 281 NOD mice. The
      protection from diabetes conferred by NK T cells is thus associated with a Th2
      shift within islets directed against autoantigen such as glutamic acid
      decarboxylase. Our findings also demonstrate the key role of IL-4.

PMID- 11238618
TI  - Primary hepatocytes from mice treated with IL-2/IL-12 produce T cell
      chemoattractant activity that is dependent on monokine induced by IFN-gamma (Mig)
      and chemokine responsive to gamma-2 (Crg-2).
AB  - The IFN-gamma-inducible proteins monokine induced by IFN-gamma (Mig) and
      chemokine responsive to gamma-2 (Crg-2) can contribute to IL-12-induced
      antiangiogenic and leukocyte-recruiting activities, but the extent to which
      leukocytes vs parenchymal cells in different organs contribute to the production
      of these molecules remains unclear. The results presented herein show that IFN
      gamma-dependent induction of Mig and Crg-2 gene expression can occur in many
      nonlymphoid organs, and these genes are rapidly induced in purified hepatocytes
      isolated from mice treated with IL-2 plus IL-12, or from Hepa 1-6 hepatoma cells
      treated in vitro with IFN-gamma. In addition to depending on IFN-gamma, the
      ability of IL-12 or IL-2/IL-12 to induce Mig and Crg-2 gene expression in
      purified hepatocytes also is accompanied by the coordinate up-regulation of the
      IFN-gamma R alpha and beta-chains, in the absence of IL-12R components.
      Supernatants of primary hepatocytes obtained from mice treated in vivo with IL
      2/IL-12 or from hepatocytes treated in vitro with IFN-gamma contain increased
      chemotactic activity for enriched human and mouse CD3(+) T cells, as well as
      mouse DX5(+) NK cells. The hepatocyte-derived chemotactic activity for mouse T
      cells but not NK cells was ablated by Abs specific for Mig and Crg-2. These
      results suggest that parenchymal cells in some organs may contribute
      substantially to initiation and/or amplification of inflammatory or antitumor
      responses.

PMID- 11238619
TI  - Mouse CD94 participates in Qa-1-mediated self recognition by NK cells and
      delivers inhibitory signals independent of Ly-49.
AB  - Inhibitory receptors expressed on NK cells recognize MHC class I molecules and
      transduce negative signals to prevent the lysis of healthy autologous cells. The
      lectin-like CD94/NKG2 heterodimer has been studied extensively as a human
      inhibitory receptor. In contrast, in mice, another lectin-like receptor, Ly-49,
      was the only known inhibitory receptor until the recent discovery of CD94/NKG2
      homologues in mice. Here we describe the expression and function of mouse CD94
      analyzed by a newly established mAb. CD94 was detected on essentially all NK and
      NK T cells as well as small fractions of T cells in all mouse strains tested. Two
      distinct populations were identified among NK and NK T cells, CD94(bright) and
      CD94(dull) cells, independent of Ly-49 expression. The anti-CD94 mAb completely
      abrogated the inhibition of target killing mediated by NK recognition of Qa-1/Qdm
      peptide on target cells. Importantly, CD94(bright) but not CD94(dull) cells were
      found to be functional in the Qa-1/Qdm-mediated inhibition. In the presence of
      the mAb, activated NK cells showed substantial cytotoxicity against autologous
      target cells as well as enhanced cytotoxicity against allogeneic and "missing
      self" target cells. These results suggest that mouse CD94 participates in the
      protection of self cells from NK cytotoxicity through the Qa-1 recognition,
      independent of inhibitory receptors for classical MHC class I such as Ly-49.

PMID- 11238620
TI  - The maturation of dendritic cells results in postintegration inhibition of HIV-1
      replication.
AB  - Maturation of dendritic cells (DC) is known to result in decreased capacity to
      produce HIV due to postentry block of its replicative cycle. In this study, we
      compared the early phases of this cycle in immature DC (iDC) and mature DC (mDC)
      generated from monocytes cultured with GM-CSF and IL-4, trimeric CD40 ligand
      (DC(CD40LT)), or monocyte-conditioned medium (DC(MCM)) being added or not from
      day 5. Culture day 8 cells exposed to X4 HIV-1(LAI) or R5 HIV-1(Ba-L) were
      analyzed by semiquantitative R-U5 PCR, which detects total HIV DNA. CXC chemokine
      receptor 4(low) (CXCR4(low)) CCR5(+) iDC harbored similar viral DNA amounts when
      exposed to either strain. HIV-1(LAI) entered more efficiently into DC(CD40LT) or
      DC(MCM) with up-regulated CXCR4. CCR5(low) DC(CD40LT) still allowed entry of HIV
      1(Ba-L), whereas CCR5(-) DC(MCM) displayed reduced permissivity to this virus.
      Comparing amounts of late (long terminal repeat (LTR)-gag PCR) and total (R-U5
      PCR) viral DNA products showed that HIV-1(Ba-L) reverse transcription was more
      efficient than that of HIV-1(LAI), but was not affected by DC maturation.
      Southern blot detection of linear, circular, and integrated HIV DNA showed that
      maturation affected neither HIV-1 nuclear import nor integration. When assessing
      virus transcription by exposing iDC to pNL4-3.GFP or pNL4-3.Luc viruses
      pseudotyped with the G protein of vesicular stomatitis virus (VSV-G), followed by
      culture with or without CD40LT or MCM, GFP and luciferase activities decreased by
      60-75% in mDC vs iDC. Thus, reduced HIV replication in mDC is primarily due to a
      postintegration block occurring mainly at the transcriptional level. We could not
      relate this block to altered expression and nuclear localization of NF-kappa B
      proteins and SP1 and SP3 transcription factors.

PMID- 11238621
TI  - IL-10 is required for regulatory T cells to mediate tolerance to alloantigens in
      vivo.
AB  - We present evidence that donor-reactive CD4(+) T cells present in mice tolerant
      to donor alloantigens are phenotypically and functionally heterogeneous. CD4(+) T
      cells contained within the CD45RB(high) fraction remained capable of mediating
      graft rejection when transferred to donor alloantigen-grafted T cell-depleted
      mice. In contrast, the CD45RB(low) CD4(+) and CD25(+)CD4(+) populations failed to
      induce rejection, but rather, were able to inhibit rejection initiated by naive
      CD45RB(high) CD4(+) T cells. Analysis of the mechanism of immunoregulation
      transferred by CD45RB(low) CD4(+) T cells in vivo revealed that it was donor Ag
      specific and could be inhibited by neutralizing Abs reactive with IL-10, but not
      IL-4. CD45RB(low) CD4(+) T cells from tolerant mice were also immune suppressive
      in vitro, as coculture of these cells with naive CD45RB(high) CD4(+) T cells
      inhibited proliferation and Th1 cytokine production in response to donor
      alloantigens presented via the indirect pathway. These results demonstrate that
      alloantigen-specific regulatory T cells contained within the CD45RB(low) CD4(+) T
      cell population are responsible for the maintenance of tolerance to donor
      alloantigens in vivo and require IL-10 for functional activity.

PMID- 11238622
TI  - Critical requirement for the membrane-proximal cytosolic tyrosine residue for
      CD28-mediated costimulation in vivo.
AB  - The YMNM motif that exists in the CD28 cytoplasmic domain is known as a binding
      site for phosphatidylinositol 3-kinase and Grb-2 and is considered to be
      important for CD28-mediated costimulation. To address the role of the YMNM motif
      in CD28 cosignaling in primary T cells, we generated transgenic mice on a CD28
      null background that express a CD28 mutant lacking binding ability to
      phosphatidylinositol 3-kinase and Grb-2. After anti-CD3 and anti-CD28 Ab
      stimulation in vitro, the initial proliferative response and IL-2 secretion in
      CD28 Y189F transgenic T cells were severely compromised, while later responses
      were intact. In contrast to anti-CD3 and anti-CD28 Ab stimulation, PMA and anti
      CD28 Ab stimulation failed to induce IL-2 production from CD28 Y189F transgenic T
      cells at any time point. Using the graft-vs-host reaction system, we assessed the
      role of the YMNM motif for CD28-mediated costimulation in vivo and found that
      CD28 Y189F transgenic spleen cells failed to engraft and could not induce acute
      graft-vs-host reaction. Together, these results suggest that the membrane
      proximal tyrosine of CD28 is required for costimulation in vivo. Furthermore,
      these results indicate that the results from in vitro assays of CD28-mediated
      costimulation may not always correlate with T cell activation in vivo.

PMID- 11238623
TI  - MHC-II-independent CD4+ T cells induce colitis in immunodeficient RAG-/- hosts.
AB  - CD4(+) alpha beta T cells from either normal C57BL/6 (B6) or MHC-II-deficient (A
      alpha(-/-) or A beta(-/-)) B6 donor mice engrafted into congenic immunodeficient
      RAG1(-/-) B6 hosts induced an aggressive inflammatory bowel disease (IBD).
      Furthermore, CD4(+) T cells from CD1d(-/-) knockout (KO) B6 donor mice but not
      those from MHC-I(-/-) (homozygous transgenic mice deficient for beta(2)
      microglobulin) KO B6 mice induced a colitis in RAG(-/-) hosts. Abundant numbers
      of in vivo activated (CD69(high)CD44(high)CD28(high)) NK1(+) and NK1(-) CD4(+) T
      cells were isolated from the inflamed colonic lamina propria (cLP) of
      transplanted mice with IBD that produced large amounts of TNF-alpha and IFN-gamma
      but low amounts of IL-4 and IL-10. IBD-associated cLP Th1 CD4(+) T cell
      populations were polyclonal and MHC-II-restricted when derived from normal B6
      donor mice, but oligoclonal and apparently MHC-I-restricted when derived from MHC
      II-deficient (A alpha(-/-) or A beta(-/-)) B6 donor mice. cLP CD4(+) T cell
      populations from homozygous transgenic mice deficient for beta(2)-microglobulin
      KO B6 donor mice engrafted into RAG(-/-) hosts were Th2 and MHC-II restricted.
      These data indicate that MHC-II-dependent as well as MHC-II-independent CD4(+) T
      cells can induce a severe and lethal IBD in congenic, immunodeficient hosts, but
      that the former need the latter to express its IBD-inducing potential.

PMID- 11238624
TI  - Endogenous glucocorticoids play a positive regulatory role in the anti-keyhole
      limpet hemocyanin in vivo antibody response.
AB  - Glucocorticoids (GCs) are commonly reported to be immunosuppressive. Studies that
      support this involve the administration of synthetic GCs such as dexamethasone at
      high pharmacological doses and using in vitro assay systems that may have limited
      relevance to the role of GCs during normal in vivo immune responses. Therefore,
      the following experiments tested the conclusion that GCs are generally
      immunosuppressive. Adult male Sprague Dawley rats received adrenalectomy (ADX) or
      sham surgery. ADX rats were given either basal corticosterone (CORT) replacement
      in their drinking water (25 microg/ml) or no CORT. Rats were immunized with
      keyhole limpet hemocyanin (KLH), and blood samples were taken. ADX rats with no
      CORT replacement had reduced anti-KLH IgM and IgG responses compared with sham
      operated controls. ADX rats that received basal CORT replacement had partially
      restored anti-KLH IgM, but still had suppressed anti-KLH IgG. Administration of
      GC receptor type I (RU28318) and type II (RU40555) receptor antagonists also
      reduced the anti-KLH IgM and IgG responses. ADX rats that received both basal
      CORT replacement and low dose injections of CORT on days 5 and 7 after KLH had
      anti-KLH IgG levels equal to those of sham-operated controls. Finally, the GC
      elevation 4-7 days after immunization may play a role in stimulating the IgM to
      IgG2a switch. GC receptor blockade reduced the anti-KLH IgG2a and splenic IFN
      gamma, but not the anti-KLH IgG1, response. Given that IFN-gamma is an important
      regulator of the IgM to IgG2a switch, it is possible that the small rise in GC
      found 4-7 days after KLH facilitates IgG2a isotype switching.

PMID- 11238625
TI  - Antiviral cytotoxic T cells cross-reactively recognize disparate peptide
      determinants from related viruses but ignore more similar self- and foreign
      determinants.
AB  - We have investigated the reactivities of cytotoxic T (Tc) cells against the two
      immunodominant, H-2K(k)-restricted determinants from the FLAVIVIRUS: Murray
      Valley encephalitis virus (MVE), MVE(1785) (REHSGNEI) and MVE(1971) (DEGEGRVI).
      The respective Tc cell populations cross-reactively lysed target cells pulsed
      with determinants from the MVE(1785)- and MVE(1971)-corresponding positions of
      six other flaviviruses, despite low sequence homology in some cases. Notably,
      anti-MVE(1785) Tc cells recognized a determinant (TDGEERVI) that shares with the
      determinant used for stimulation only the carboxyl-terminal amino acid residue,
      one of two H-2K(k) anchor residues. These reactivity patterns were also observed
      in peptide-dependent IFN-gamma production and the requirements for in vitro
      restimulation of memory Tc cells. However, the broad cross-reactivity appeared to
      be limited to flavivirus-derived determinants, as none of a range of determinants
      from endogenous mouse-derived sequences, similar to the MVE-determinants, were
      recognized. Neither were cells infected with a number of unrelated viruses
      recognized. These results raise the paradox that virus-immune Tc cell responses,
      which are mostly directed against only a few "immunodominant" viral determinants,
      are remarkably peptide cross-reactive.

PMID- 11238626
TI  - Human CD1d functions as a transplantation antigen and a restriction element in
      mice.
AB  - To study the potential functions of human CD1d (hCD1d), we developed transgenic
      (Tg) mice that ectopically express hCD1d under the control of H-2K(b) promoter.
      High levels of hCD1d expression were detected in all Tg tissues tested. Skin
      grafts from the K(b)/hCD1d Tg mice were rapidly rejected by MHC-matched non-Tg
      recipient mice, suggesting that hCD1d can act as transplantation Ags.
      Furthermore, we were able to elicit hCD1d-restricted CD8(+) CTLs from mice
      immunized with K(b)/hCD1d Tg splenocytes. These CTLs express TCR rearrangements
      that are distinct from invariant TCR of NK T cells, and secrete significant
      amounts of IFN-gamma upon Ag stimulation. Analysis with various hCD1d-expressing
      targets and use of Ag presentation inhibitors indicated the recognition of hCD1d
      by CTLs did not involve species or tissue-specific ligands nor require the
      processing pathways of endosomes or proteasomes. Additionally, the reactivity of
      hCD1d-specific CTLs was not affected by acid stripping followed by brefeldin A
      treatment, suggesting that CTLs may recognize a ligand/hCD1d complex that is
      resistant to acid denaturation, or empty hCD1d molecules. Our results show that
      hCD1d can function as an alloantigen for CD8(+) CTLs. The hCD1d Tg mice provide a
      versatile model for the study of hCD1d-restricted cytolytic responses to
      microbial Ags.

PMID- 11238627
TI  - A critical role for p38 mitogen-activated protein kinase in the maturation of
      human blood-derived dendritic cells induced by lipopolysaccharide, TNF-alpha, and
      contact sensitizers.
AB  - We investigated the involvement of mitogen-activated protein kinases (MAPKs) in
      the maturation of CD83(-) dendritic cells (DC) derived from human blood
      monocytes. Maturating agents such as LPS and TNF-alpha induced the
      phosphorylation of members of the three families of MAPK (extracellular signal
      regulated kinase l/2, p46/54 c-Jun N-terminal kinase, and p38 MAPK). SB203580, an
      inhibitor of the p38 MAPK, but not the extracellular signal-regulated kinase l/2
      pathway blocker PD98059, inhibited the up-regulation of CD1a, CD40, CD80, CD86,
      HLA-DR, and the DC maturation marker CD83 induced by LPS and TNF-alpha. In
      addition, SB203580 inhibited the enhancement of the allostimulatory capacity and
      partially prevented the down-regulation of FITC-dextran uptake induced by LPS and
      TNF-alpha. Likewise, SB203580 partially prevented the up-regulation of IL-1alpha,
      IL-1beta, IL-lRa, and TNF-alpha mRNA upon stimulation with LPS and TNF-alpha, as
      well as the release of bioactive TNF-alpha induced by LPS. DC maturation induced
      by the contact sensitizers 2,4-dinitrofluorobenzene and NiSO(4), as seen by the
      up-regulation of CD80, CD86, and CD83, was also coupled to the phosphorylation of
      p38 MAPK, and was inhibited by SB203580. The irritants SDS and benzalkonium
      chloride that do not induce DC maturation did not trigger p38 MAPK
      phosphorylation. Together, these data indicate that phosphorylation of p38 MAPK
      is critical for the maturation of immature DC. These results also suggest that
      p38 MAPK phosphorylation in DC may become useful for the identification of
      potential skin contact sensitizers.

PMID- 11238628
TI  - Human vascular endothelial cells stimulate a lower frequency of alloreactive CD8+
      pre-CTL and induce less clonal expansion than matching B lymphoblastoid cells:
      development of a novel limiting dilution analysis method based on CFSE labeling
      of lymphocytes.
AB  - We have previously shown that human endothelial cells (EC) are less efficient
      than professional APC, e.g., B lymphoblastoid cells (BLC), at stimulating
      allogeneic CD8(+) T cells to develop into CTL. In this study we describe FACS
      based limiting dilution analyses using the dilution of the intracellular dye CFSE
      as an indicator of CD8(+) T cell alloactivation and expansion with significantly
      increased sensitivity compared with conventional, cytotoxicity-based assays. In
      addition, this assay permits the relative size of clonal CTL populations that are
      generated in individual CD8(+) T cell cultures to be determined (clonal burst
      size). We have applied this method to quantitatively compare the generation of
      CTL at the clonal level following stimulation of allogeneic CD8(+) T cells by
      either BLC or HUVEC derived from the same donor. CD8(+) T cells expanded by
      allostimulation were identified as CD8(+), CFSE(low) cells and were categorized
      as CTL by the expression of intracellular perforin and IFN-gamma. Precursor
      frequencies for EC-stimulated CTL were 5- to 40-fold (mean, 7.5-fold) lower
      compared with BLC-stimulated CTL (p < 0.01). Concomitantly, the average clonal
      burst sizes in EC-stimulated CTL cultures were significantly smaller than those
      in conventional CTL cultures, primarily due to the occurrence of some very large
      clone sizes exclusively with BLC stimulation. Although EC-stimulated CTL were
      generated only from the memory subset of CD8(+) T cells, BLC-stimulated very
      large burst sizes of CTL were observed from both naive and memory CD8(+) T cell
      precursors. These data establish that both a lower frequency of reactive
      precursors and more limited clonal expansion, but not regulatory T cells,
      contribute to the reduced capacity of EC to promote alloreactive CTL
      differentiation compared with that of professional APC.

PMID- 11238629
TI  - Inhibition of the MEK/ERK signaling pathway blocks a subset of B cell responses
      to antigen.
AB  - Signal transduction initiated by B cell Ag receptor (BCR) cross-linking plays an
      important role in the development and activation of B cells. Therefore,
      considerable effort has gone into determining the biochemical signaling events
      initiated by the BCR and delineating which events participate in specific
      biological responses to Ag. We used two inhibitors of mitogen-activated protein
      kinase/extracellular signal-regulated kinase kinase (MEK) 1 and MEK2, PD98059,
      and U0126, to assess the role the Ras-mitogen-activated protein kinase pathway
      plays in several BCR-induced responses. PD98059 or U0126 treatment substantially
      inhibited the BCR-induced activation of the extracellular signal-regulated kinase
      (ERK) forms of mitogen-activated protein kinase in the immature B cell line WEHI
      231, in immature splenic B cells, and in mature splenic B cells. However, MEK-ERK
      inhibition did not block BCR-induced growth arrest or apoptosis of WEHI-231 cells
      or apoptosis of immature splenic B cells, indicating that the MEK-ERK pathway is
      not required for these events. In contrast, PD98059 and U0126 treatment did
      inhibit the up-regulation of specific BCR-induced proteins, including the
      transcription factor Egr-1 in WEHI-231 and mature splenic B cells, and the CD44
      adhesion molecule and CD69 activation marker in mature splenic B cells. Moreover,
      both inhibitors suppressed BCR-induced proliferation of mature splenic B cells,
      in the absence and in the presence of IL-4. Therefore, activation of the MEK-ERK
      pathway is necessary for a subset of B cell responses to Ag.

PMID- 11238630
TI  - CD83 is an I-type lectin adhesion receptor that binds monocytes and a subset of
      activated CD8+ T cells [corrected].
AB  - To help determine CD83 function, a cDNA encoding a soluble protein containing the
      CD83 extracellular domain was fused with a mutated human IgG1 constant region
      (CD83Ig) and expressed by stable transfection of Chinese hamster ovary cells.
      Purified CD83Ig bound to peripheral blood monocytes and a subset of activated
      CD3(+)CD8(+) lymphocytes but did not bind to FcR. Monocytes that had adhered to
      plastic lost their ability to bind to CD83Ig after 90 min of in vitro incubation.
      CD83Ig bound to two of five T cell lines tested, HPB-ALL and Jurkat. The binding
      to HPB-ALL cells significantly increased when they were grown at a low pH (pH
      6.5), whereas binding to Jurkat cells increased after apoptosis was induced with
      anti-Fas mAb. B cell and monocytic lines did not bind CD83Ig and neither did
      CD56(+) NK cells or granulocytes. Full-length CD83 expressed by a transfected
      carcinoma line mediated CD83-dependent adhesion to HPB-ALL cells. CD83Ig
      immunoprecipitated and immunoblotted a 72-kDa protein from HPB-ALL cells. Binding
      of CD83Ig to HPB-ALL cells was eliminated by neuraminidase treatment of the
      cells. We conclude that CD83 is an adhesion receptor with a counterreceptor
      expressed on monocytes and a subset of activated or stressed T lymphocytes, and
      that interaction between CD83 and its counterreceptor is dependent upon the state
      of glycosylation of a 72-kDa counterreceptor by sialic acid residues. In view of
      the selectivity of the expression of CD83 and its ligand, we postulate that the
      interaction between the two plays an important role in the induction and
      regulation of immune responses.

PMID- 11238631
TI  - Biphasic regulation of NF-kappa B activity underlies the pro- and anti
      inflammatory actions of nitric oxide.
AB  - Expression of inducible NO synthase (iNOS) by macrophages is a prerequisite for
      the production of high output NO, which mediates many bactericidal and
      tumoricidal actions of these immune cells. The expression of iNOS in mammalian
      cells is governed predominantly by the transcription factor, NF-kappa B, which
      regulates the expression of many host defense proteins. In the present study, we
      characterize a novel, biphasic effect of NO on NF-kappa B activity in murine
      macrophages. This mechanism depends on the local concentration of NO and enables
      it both to up- and down-regulate the expression of host defense proteins
      including iNOS, cyclooxygenase-2, and IL-6. This biphasic activity of NO appears
      to play a pivotal role in the time course of activation of these immune cells
      and, by inference, in facilitating the initiation of a defense response against
      pathogenic stimuli and in its termination to limit tissue damage. This mechanism
      may explain at least in part the reported ability of NO to act in both a pro- and
      anti-inflammatory manner.

PMID- 11238632
TI  - The Fc receptor for IgG expressed in the villus endothelium of human placenta is
      Fc gamma RIIb2.
AB  - To evaluate the potential role of human placental endothelial cells in the
      transport of IgG from maternal to fetal circulation, we studied Fc gamma receptor
      (Fc gamma R) expression by immunohistology and immunoblotting. Several pan-Fc
      gamma RII Abs that label the placental endothelium displayed a distribution
      pattern that correlated well with transport functions, being intense in the
      terminal villus and nil in the cord. In contrast, the MHC class 1-like IgG
      transporter, FcRn, and the classical Fc gamma RIIa were not expressed in
      transport-related endothelium of the placenta. Our inference, that Fc gamma RIIb
      was the likely receptor, we confirmed by analyzing purified placental villi,
      enriched in endothelium, by immunoblotting with a new Ab specific for the
      cytoplasmic tail of Fc gamma RIIb. These experiments showed that the Fc gamma RII
      expressed in villus endothelium was the b2 isoform whose cytoplasmic tail is
      known to include a phosphotyrosyl-based motif that inhibits a variety of immune
      responses. We suggest that this receptor is perfectly positioned to transport IgG
      although as well it may scavenge immune complexes.

PMID- 11238633
TI  - IL-12 inhibition of endothelial cell functions and angiogenesis depends on
      lymphocyte-endothelial cell cross-talk.
AB  - In vivo IL-12-dependent tumor inhibition rests on the ability of IL-12 to
      activate a CD8-mediated cytotoxicity, inhibit angiogenesis, and cause vascular
      injury. Although in vivo studies have shown that such inhibition stems from
      complex interactions of immune cells and the production of IFN-gamma and other
      downstream angiostatic chemokines, the mechanisms involved are still poorly
      defined. Here we show that IL-12 activates an anti-angiogenic program in Con A
      activated mouse spleen cells (activated spc) or human PBMC (activated PBMC). The
      soluble factors they release in its presence arrest the cycle of endothelial
      cells (EC), inhibit in vitro angiogenesis, negatively modulate the production of
      matrix metalloproteinase-9, and the ability of EC to adhere to vitronectin and up
      regulate ICAM-1 and VCAM-1 expression. These effects do not require direct cell
      cell contact, yet result from continuous interaction between activated lymphoid
      cells and EC. We used neutralizing Abs to show that the IFN-inducible protein-10
      and monokine-induced by IFN-gamma chemokines are pivotal in inducing these
      effects. Experiments with nu/nu mice, nonobese diabetic-SCID mice, or activated
      spc enriched in specific cell subpopulations demonstrated that CD4(+), CD8(+),
      and NK cells are all needed to mediate the full anti-angiogenetic effect of IL
      12.

PMID- 11238634
TI  - Absence of CTLA-4 lowers the activation threshold of primed CD8+ TCR-transgenic T
      cells: lack of correlation with Src homology domain 2-containing protein tyrosine
      phosphatase.
AB  - To examine the role of CTLA-4 in controlling Ag-specific CD8(+) T cell
      activation, TCR-transgenic/CTLA-4 wild-type or -deficient mice were generated in
      a recombination-activating gene 2-deficient background. Naive T cells from these
      mice responded comparably whether or not CTLA-4 was expressed. In contrast,
      primed T cells responded more vigorously if they lacked CTLA-4 expression. We
      took advantage of the difference between naive and primed T cell responses to
      approach the mechanism of CTLA-4 function. Single-cell analyses demonstrated that
      a greater fraction of CTLA-4-deficient cells responded to a fixed dose of Ag
      compared with CTLA-4-expressing cells, whereas the magnitude of response per cell
      was comparable. A shift in the dose-response curve to APCs was also observed such
      that fewer APCs were required to activate CTLA-4-deficient T cells to produce
      intracellular IFN-gamma and to proliferate. These results suggest that CTLA-4
      controls the threshold of productive TCR signaling. Biochemical analysis
      comparing stimulated naive and primed TCR-transgenic cells revealed no obvious
      differences in expression of total CTLA-4, tyrosine-phosphorylated CTLA-4, and
      associated Src homology domain 2-containing protein tyrosine phosphatase. Thus,
      the biochemical mechanism explaining the differential inhibitory effect of CTLA-4
      on naive and primed CD8(+) T cells remains unclear.

PMID- 11238635
TI  - CTLA-4 blockade enhances the CTL responses to the p53 self-tumor antigen.
AB  - p53 is an attractive target for cancer immunotherapy because it is overexpressed
      in a high proportion of many different types of tumors. However, it is also
      expressed in normal tissues and acts as a toleragen in vivo. Previously, detailed
      examination of the repertoire specific for the murine p53(261-269) epitope in
      conventional and p53-deficient mice demonstrated that because of expression of
      p53, the CD8(+) T cells that respond to this epitope express low-affinity TCRs.
      It has been reported that tolerance to tumor Ags can be broken by in vivo
      administration of anti-CTLA-4 mAb. With the goal of overriding tolerance and
      achieving optimal activation of p53-specific CTL, the current study has assessed
      the effect of anti-CTLA-4 mAb on the p53-specific repertoire. It was found that
      blockade of CTLA-4 engagement at the time of antigenic stimulation induced a
      vigorous amplification of the CTL responses to p53 as well as proportionate
      expansion of the memory T cell pool. This effect was dependent on the presence of
      CD4(+) T cell help and correlated with an enhancement of helper function.
      However, anti-CTLA-4 treatment did not enhance the avidity of the resultant p53
      specific CTL populations and, therefore, could not reverse this important
      consequence of tolerance.

PMID- 11238636
TI  - Novel single nucleotide polymorphisms in the distal IL-10 promoter affect IL-10
      production and enhance the risk of systemic lupus erythematosus.
AB  - Family studies of first-degree relatives and analysis of twins indicate that as
      much as 75% of the differences in quantitative IL-10 production in man derive
      from heritable genetic factors. Studies of single nucleotide polymorphisms (SNP)
      in the proximal 1.0 kb of the IL-10 promoter have yielded inconsistent
      association with IL-10 production and variable results in promoter-reporter
      studies. However, in normal donors, an association of quantitative production
      with certain alleles of the IL-10.R short tandem repeat polymorphism at -4.0 kb
      suggested that SNPs in the more distal promoter might be informative. We have
      identified seven novel SNP sites in the genomic sequence of the first 4 kb of the
      IL-10 promoter region 5' to the ATG start site from Caucasian individuals with
      either a high or a low IL-10 production phenotype. We have also identified eight
      SNP haplotypes in the distal promoter that segregate with significant differences
      in quantitative IL-10 production in normal donors. These SNPs are significantly
      associated with systemic lupus erythematosus in African-Americans and may define
      one component of the genetic susceptibility to systemic lupus erythematosus in
      this group.

PMID- 11238637
TI  - The repertoire of killer cell Ig-like receptor and CD94:NKG2A receptors in T
      cells: clones sharing identical alpha beta TCR rearrangement express highly
      diverse killer cell Ig-like receptor patterns.
AB  - Killer cell Ig-like receptor (KIR) and CD94:NKG2A molecules were first defined as
      human NK cell receptors (NKR), but now are known to be expressed and to function
      on subpopulations of T cells. Here the repertoires of KIR and CD94:NKG2A
      expression by T cells from two donors were examined and compared with their
      previously defined NK cell repertoires. T cell clones generated from peripheral
      blood of both donors expressed multiple NKR in different combinations and used
      the range of receptors expressed by NK cells. In both donors alpha beta T cells
      less frequently expressed the inhibitory receptors CD94:NKG2A and KIR2DL1 than
      either gamma delta T cells or NK cells. In contrast to NK cells, not all NKR(+) T
      cells expressed an inhibitory receptor for autologous HLA class I. This lack of
      specific inhibitory NKR was especially apparent on alpha beta T cells of one
      donor. Overall, alpha beta T cells exhibited a distinct pattern of NKR expression
      different from that of gamma delta T and NK cells, which expressed highly similar
      NKR repertoires. In one donor, analysis of TCR rearrangement revealed a dominant
      subset of NKR(+) T cells sharing identical TCR alpha- and beta-chains.
      Remarkably, among 55 T cell clones sharing the same TCR alpha beta rearrangement
      18 different KIR phenotypes were seen, suggesting that KIR expression was
      initiated subsequently to TCR rearrangement.

PMID- 11238638
TI  - Differential expression of leukocyte receptor complex-encoded Ig-like receptors
      correlates with the transition from effector to memory CTL.
AB  - The human leukocyte receptor complex (LRC) on chromosome 19q13.4 encodes Ig
      superfamily receptors expressed on hemopoietic cells. Killer Ig-like receptors
      (KIR) are expressed in cytotoxic lymphocytes but other LRC molecules (Ig-like
      transcript(ILT)/leukocyte Ig-like receptor (LIR)) are more ubiquitous. We
      investigated expression of the ILT2/LIR1 inhibitory receptor compared with the
      related KIR. Both ILT2/LIR1 and KIR were expressed by peripheral CD8(+) T cells
      with a memory/effector phenotype. ILT2/LIR1(+) T cells demonstrated diverse TCRBV
      repertoires in contrast to KIR(+) T cells, while numbers of peripheral
      ILT2/LIR1(+) T cells were greater than KIR(+) T cells and the majority of
      ILT2/LIR1(+) T cells did not coexpress KIR. Analysis of CD8(+) T cells with
      specific HLA class I tetramers confirmed this pattern of expression, indicating
      differential regulation of LRC gene expression in T lymphocytes. Only a minor
      proportion of ILT2/LIR1(+) KIR(-) clones survived in vitro cloning, were more
      susceptible to anti-CD3 or cognate peptide induced cell death than KIR(+) T cells
      and exhibited lower levels of the Bcl-2 survival molecule. Our results indicate a
      sequential program of LRC-encoded receptor expression with initial ILT2/LIR1
      expression in effector T cells and KIR gene transcription in the minor proportion
      of expanded clones which survives activation-induced cell death to become long
      term memory T cells.

PMID- 11238639
TI  - Organization and functional analysis of the mouse transporter associated with
      antigen processing 2 promoter.
AB  - In accordance with the key role of MHC class I molecules in the adaptive immune
      response against viruses, they are expressed by most cells, and their expression
      can be enhanced by cytokines. The assembly and cell surface expression of class I
      complexes depend on a continuous peptide supply. The peptides are generated
      mainly by the proteasome and are transported to the endoplasmic reticulum by a
      peptide transport pump consisting of two subunits, TAP1 and TAP2. The proteasome
      low molecular weight polypeptide (2 and 7), as well as TAP (1 and 2) genes, are
      coordinately regulated and are induced by IFNs. Despite this coordinate
      regulation, examination of tumors shows that these genes can be discordantly down
      regulated. In pursuing a molecular explanation for these observations, we have
      characterized the mouse TAP2 promoter region and 5'-flanking sequence. We show
      that the 5' untranslated regions of TAP2 genes have a characteristic genomic
      organization that is conserved in both the mouse and the human. The mouse TAP2
      promoter belongs to a class of promoters that lack TATA boxes but contain a MED1
      (multiple start site element downstream) sequence. Accordingly, transcription is
      initiated from multiple sites within a 100-nucleotide window. An IFN regulatory
      factor 1 (IRF1)/IRF2 binding site is located in this region and is involved in
      both basal and IRF1-induced TAP2 promoter activity. The implication of the
      extensive differences found among the promoters of class I heavy chain, low
      molecular weight polypeptide, and TAP genes, all encoding proteins involved in Ag
      presentation, is discussed.

PMID- 11238640
TI  - Anti-peptide antibody blocks peptide binding to MHC class I molecules in the
      endoplasmic reticulum.
AB  - The finding that MHC class I molecules are physically associated with the TAP
      transporter has suggested that peptides may be directly transported into the
      binding groove of the class I molecules rather than into the lumen of the
      endoplasmic reticulum (ER) where they subsequently would encounter class I
      molecules by diffusion. Such a mechanism would protect peptides from peptidases
      in the ER and/or escaping back into the cytoplasm. However, we find that an anti
      peptide Ab that is cotranslationally transported into the ER prevents TAP
      transported peptides from being presented on class I molecules. The Ab only
      blocks the binding of its cognate peptide (SIINFEKL) but not other peptides
      (KVVRFKDL, ASNENMETM, and FAPGNYPAL). Therefore, most TAP-transported peptides
      must diffuse through the lumen of the ER before binding stably to MHC class I
      molecules.

PMID- 11238641
TI  - Physical map and expression profile of genes of the telomeric class I gene region
      of the rat MHC.
AB  - The rat is an important model for studying organ graft rejection and
      susceptibility to certain complex diseases. The MHC, the RT1 complex, plays a
      decisive role in controlling these traits. We have cloned the telomeric class I
      region of the RT1 complex, RT1-C/E/M, of the BN inbred rat strain in a contig of
      overlapping P1-derived artificial chromosome clones encompassing approximately 2
      Mb, and present a physical map of this MHC region. Forty-five class I exon 4
      hybridizing BAM:HI fragments were detected, including the previously known rat
      class I genes RT1-E, RT-BM1, RT1-N, RT1-M2, RT1-M3, and RT1-M4. Twenty-six non
      class I genes known to map to the corresponding part of the human and mouse MHC
      were tested and could be fine mapped in the RT1-C/E/M region at orthologous
      position. Four previously known microsatellite markers were fine mapped in the
      RT1-C/E/M region and found to occur in multiple copies. In addition, a new,
      single-copy polymorphic microsatellite has been defined. The expression profiles
      of several class I genes and the 26 non-class I genes were determined in 13
      different tissues and exhibited restricted patterns in most cases. The data
      provide further molecular information on the MHC for analyzing disease
      susceptibility and underline the usefulness of the rat model.

PMID- 11238642
TI  - A 3'-transcribed region of the HLA-A2 gene mediates posttranscriptional
      stimulation by IFN-gamma.
AB  - The expression of several MHC class I genes is up-regulated at the
      transcriptional level by IFN-gamma. Posttranscriptional mechanisms also have been
      implicated, but not well characterized. To investigate the mechanism of IFN-gamma
      stimulation of the human MHC class I gene HLA-A2, several human tumor cell lines
      were transfected with reporter gene constructs driven by the HLA-A2 promoter. We
      have previously shown that the extended 525-bp HLA-A2 promoter alone, which
      includes a 5' IFN-stimulated response element consensus sequence, is not
      sufficient for IFN-gamma response in either K562 or Jurkat cells. In the current
      study, stable transfection of a genomic HLA-A2 gene construct, containing both 5'
      and 3'-flanking sequences, resulted in stimulation of the gene by IFN-gamma.
      Nuclear run-on assays revealed that, unlike other class I genes, IFN-gamma
      stimulation of HLA-A mRNA accumulation occurs almost entirely through
      posttranscriptional mechanisms. RNA stability assays showed that the effect is
      not mediated by alteration of the half-life of the HLA-A2 mRNA. Formation of the
      3' end was unaffected by IFN-gamma treatment. Sequences that mediate the majority
      of IFN-gamma induction of HLA-A2 mRNA reside in a 127-bp 3'-transcribed region of
      the gene. This region contains the terminal splice site, the usage of which is
      not affected by IFN-gamma treatment. These results demonstrate a novel
      posttranscriptional mechanism of regulation of MHC class I genes by IFN-gamma.

PMID- 11238643
TI  - Targeting Src homology 2 domain-containing tyrosine phosphatase (SHP-1) into
      lipid rafts inhibits CD3-induced T cell activation.
AB  - To study the mechanism by which protein tyrosine phosphatases (PTPs) regulate CD3
      induced tyrosine phosphorylation, we investigated the distribution of PTPs in
      subdomains of plasma membrane. We report here that the bulk PTP activity
      associated with T cell membrane is present outside the lipid rafts, as determined
      by sucrose density gradient sedimentation. In Jurkat T cells, approximately 5-
      10% of Src homology 2 domain-containing tyrosine phosphatase (SHP-1) is
      constitutively associated with plasma membrane, and nearly 50% of SHP-2 is
      translocated to plasma membrane after vanadate treatment. Similar to
      transmembrane PTP, CD45, the membrane-associated populations of SHP-1 and SHP-2
      are essentially excluded from lipid rafts, where other signaling molecules such
      as Lck, linker for activation of T cells, and CD3 zeta are enriched. We further
      demonstrated that CD3-induced tyrosine phosphorylation of these substrates is
      largely restricted to lipid rafts, unless PTPs are inhibited. It suggests that a
      restricted partition of PTPs among membrane subdomains may regulate protein
      tyrosine phosphorylation in T cell membrane. To test this hypothesis, we targeted
      SHP-1 into lipid rafts by using the N-terminal region of Lck (residues 1--14).
      The results indicate that the expression of Lck/SHP-1 chimera inside lipid rafts
      profoundly inhibits CD3-induced tyrosine phosphorylation of CD3 zeta/epsilon, IL
      2 generation, and nuclear mobilization of NF-AT. Collectively, these results
      suggest that the exclusion of PTPs from lipid rafts may be a mechanism that
      potentiates TCR/CD3 activation.

PMID- 11238644
TI  - Class I MHC expression in the yellow baboon.
AB  - MHC class I molecules play a crucial role in the immune response to pathogens and
      vaccines and in self/non-self recognition. Therefore, characterization of MHC
      class I gene expression of Papio subspecies is a prerequisite for studies of
      immunology and transplantation in the baboon (papio hamadryas). To elucidate MHC
      class I expression and variation within Papio subspecies and to further
      investigate the evolution of A and B loci in Old World primates, we have
      characterized the expressed class I repertoire of the yellow baboon (Papio
      hamadryas cynocephalus) by cDNA library screening. A total of nine distinct MHC
      class I cDNAs were isolated from a spleen cDNA library. The four A alleles and
      four B alleles obtained represent four distinct loci indicating that a
      duplication of the A and B loci has taken place in the lineage leading to these
      Old World primates. No HLA--C homologue/orthologue was found. In addition a
      single, nonclassical homologue of HLA--E was characterized. Examination of
      nucleotide and extrapolated protein sequences indicates that alleles at the two B
      loci are much more diversified than the alleles at the A loci. One of the A loci
      in particular appears to display very limited polymorphism in both Papio
      hamadryas cynocephalus and Papio hamadryas anubis subspecies. The failure to
      detect a homologue of HLA--C in the baboon provides additional evidence for the
      more recent origin of this locus in the pongidae and hominidae: Further
      comparative analysis with MHC sequences among the primate species reveals
      specific patterns of divergence and conservation within class I molecules of the
      yellow baboon.

PMID- 11238645
TI  - A structural difference limited to one residue of the antigenic peptide can
      profoundly alter the biological outcome of the TCR-peptide/MHC class I
      interaction.
AB  - The vesicular stomatitis virus (VSV) octapeptide RGYVYQGL binds to H-2K(b) and
      triggers a cytotoxic T cell response in mice. A variant peptide, RGYVYEGL (E6)
      with a glutamic acid for glutamine replacement at position 6 of the VSV peptide,
      elicits a T cell response with features that are quite different from those
      elicited by the wild-type VSV peptide. The differences found in the nature of the
      T cells responding to the E6 peptide include changes in both the V beta elements
      and the sequences of the complementarity-determining region 3 loops of their
      TCRs. Further experiments found that the E6 peptide can act as an antagonist for
      VSV-specific T cell hybridomas. To determine whether these differences in V beta
      usage, complementarity-determining region 3 sequences, and the switch from
      agonism to antagonism are caused by a conformational change on the MHC, the
      peptide, or both, we determined the crystal structure of the variant E6 peptide
      bound to H-2K(b). This structure shows that the only significant structural
      difference between H-2K(b)/E6 and the previously determined H-2K(b)/VSV is
      limited to the side chain of position 6 of the peptide, with no differences in
      the MHC molecule. Thus, a minor conformational change in the peptide can
      profoundly alter the biological outcome of the TCR-peptide/MHC interaction.

PMID- 11238646
TI  - Topology and structure of the C1q-binding site on C-reactive protein.
AB  - The host defense functions of human C-reactive protein (CRP) depend to a great
      extent on its ability to activate the classical complement pathway. The aim of
      this study was to define the topology and structure of the CRP site that binds
      C1q, the recognition protein of the classical pathway. We have previously
      reported that residue Asp(112) of CRP plays a major role in the formation of the
      C1q-binding site, while the neighboring Lys(114) hinders C1q binding. The three
      dimensional structure of CRP shows the presence of a deep, extended cleft in each
      protomer on the face of the pentamer opposite that containing the phosphocholine
      binding sites. Asp(112) is part of this marked cleft that is deep at its origin
      but becomes wider and shallower close to the inner edge of the protomer and the
      central pore of the pentamer. The shallow end of the pocket is bounded by the 112
      114 loop, residues 86-92 (the inner loop), the C terminus of the protomer, and
      the C terminus of the pentraxin alpha-helix 169-176, particularly Tyr(175).
      Mutational analysis of residues participating in the formation of this pocket
      demonstrates that Asp(112) and Tyr(175) are important contact residues for C1q
      binding, that Glu(88) influences the conformational change in C1q necessary for
      complement activation, and that Asn(158) and His(38) probably contribute to the
      correct geometry of the binding site. Thus, it appears that the pocket at the
      open end of the cleft is the C1q-binding site of CRP.

PMID- 11238647
TI  - Two MHC surface amino acid differences distinguish foreign peptide recognition
      from autoantigen specificity.
AB  - KRN T cells can recognize two self MHC alleles with differing biological
      consequences. They respond to the foreign peptide RN(42--56) bound to I-A(k) or
      alternatively initiate autoimmune arthritis by interacting with a self Ag,
      GPI(282--294), on I-A(g7). Five surface amino acid differences between the two
      MHC molecules collectively alter which peptide side chains are recognized by the
      KRN TCR. In this study, it is shown that mutation of only two of these residues,
      alpha 65 and beta 78, in I-A(k) to their I-A(g7) counterparts is sufficient to
      allow recognition of the TCR contacts from GPI(282--294). To provide a detailed
      mechanism for the specificity change, the distinct contributions of each of these
      two mutations to the global effect on peptide specificity were analyzed. The
      alpha65 mutation is shown to broaden the spectrum of amino acids permissible at
      P8 of the peptide. In contrast, the beta 78 mutation alone blocks KRN TCR
      interaction with I-A(k) and requires the simultaneous presence of the alpha 65
      mutation to preserve recognition. In the presence of the alpha 65 mutation, the
      beta 78 residue broadens peptide recognition at P3 and prevents recognition of
      the P8 L in RN(42--56), thus producing the observed specificity shift. These
      results localize the functionally relevant differences between the surfaces of
      two self-restricted MHC molecules to two residues that have counterbalanced
      positive and negative contributions to interaction with a single TCR. They
      highlight how subtle structural distinctions attributable to single amino acids
      can stand at the interface between foreign Ag responsiveness and pathogenic
      autoreactivity.

PMID- 11238648
TI  - Rapidly fatal leishmaniasis in resistant C57BL/6 mice lacking TNF.
AB  - The resolution of infections with the protozoan parasite Leishmania major in mice
      requires a Th1 response that is closely associated with the expression of IL-12,
      IFN-gamma, and inducible NO synthase. Previous Ab neutralization studies or the
      use of mice deficient for both TNF receptors suggested that TNF plays only a
      limited role in the control of parasite replication in vivo. In this study we
      demonstrate that resistant C57BL/6 (B6.WT) mice locally infected with L. major
      rapidly succumb to progressive visceral leishmaniasis after deletion of the TNF
      gene by homologous recombination. A reduction of the parasite inoculum to 3000
      promastigotes did not prevent the fatal outcome of the disease. An influence of
      the altered morphology of secondary lymphoid organs in C57BL/6-TNF(-/-) (B6.TNF(
      /-)) mice on the course of disease could be excluded by the generation of
      reciprocal bone marrow chimeras. Although infected B6.TNF(-/-) mice mounted an L.
      major-specific IFN-gamma response and expressed IL-12, the onset of the immune
      reaction was delayed. After in vitro stimulation, B6.TNF(-/-) inflammatory
      macrophages released 10-fold less NO in response to IFN-gamma than B6.WT cells.
      However, in the presence of a costimulus, e.g., L. major infection or LPS, the
      production of NO by B6.WT and B6.TNF(-/-) macrophages was comparable. In vivo,
      inducible NO synthase protein was readily detectable in skin lesions and draining
      lymph nodes of B6.TNF(-/-) mice, but its expression was more disperse and less
      focal in the absence of TNF. These are the first data to demonstrate that TNF is
      essential for the in vivo control of L. major.

PMID- 11238649
TI  - Successful therapy of lethal murine visceral leishmaniasis with cystatin involves
      up-regulation of nitric oxide and a favorable T cell response.
AB  - The virulence of Leishmania donovani in mammals depends at least in part on
      cysteine proteases because they play a key role in CD4(+) T cell differentiation.
      A 6-fold increase in NO production was observed with 0.5 microM chicken cystatin,
      a natural cysteine protease inhibitor, in IFN-gamma-activated macrophages. In a
      45-day BALB/c mouse model of visceral leishmaniasis, complete elimination of
      spleen parasite burden was achieved by cystatin in synergistic activation with a
      suboptimal dose of IFN-gamma. In contrast to the case with promastigotes,
      cystatin and IFN-gamma inhibited the growth of amastigotes in macrophages.
      Although in vitro cystatin treatment of macrophages did not induce any NO
      generation, significantly enhanced amounts of NO were generated by macrophages of
      cystatin-treated animals. Their splenocytes secreted soluble factors required for
      the induction of NO biosynthesis, and the increased NO production was paralleled
      by a concomitant increase in antileishmanial activity. Moreover, splenocyte
      supernatants treated with anti-IFN-gamma or anti-TNF-alpha Abs suppressed
      inducible NO generation, whereas i.v. administration of these anticytokine Abs
      along with combined therapy reversed protection against infection. mRNA
      expression and flow cytometric analysis of infected spleen cells suggested that
      cystatin and IFN-gamma treatment, in addition to greatly reducing parasite
      numbers, resulted in reduced levels of IL-4 but increased levels of IL-12 and
      inducible NO synthase. Not only was this treatment curative when administered 15
      days postinfection, but it also imparted resistance to reinfection. These studies
      provide a promising alternative for protection against leishmaniasis with a
      switch of CD4(+) differentiation from Th2 to Th1, indicative of long-term
      resistance.

PMID- 11238650
TI  - Bactericidal properties of group IIA and group V phospholipases A2.
AB  - Group V phospholipase A(2) (PLA(2)) is a recently characterized 14-kDa secretory
      PLA(2) of mammalian heart and macrophage-derived cells. Group IIA PLA(2), which
      is structurally close to group V PLA(2), has been shown to kill Gram-positive
      bacteria in vitro and to prevent symptoms of Gram-positive infection in vivo. We
      studied the antibacterial properties of fully active recombinant rat group IIA
      and V PLA(2)s. Both group IIA and V PLA(2)s were highly bactericidal against Gram
      positive bacteria, including methicillin-resistant staphylococci and vancomycin
      resistant enterococci. Only high concentrations of group IIA PLA(2) showed some
      bactericidal effect against the Gram-negative bacterium Escherichia coli. Our
      results confirm that group IIA PLA(2) is a potent antibacterial enzyme against
      Gram-positive bacteria. Moreover, we show here that group V PLA(2) is a novel
      antibacterial mammalian protein, but is less potent than group IIA PLA(2). Both
      enzymes may be considered as future therapeutic agents against bacterial
      infections.

PMID- 11238651
TI  - CXC chemokine receptor 2 but not C-C chemokine receptor 1 expression is essential
      for neutrophil recruitment to the cornea in helminth-mediated keratitis (river
      blindness).
AB  - Infiltration of neutrophils and eosinophils into the mammalian cornea can result
      in loss of corneal clarity and severe visual impairment. To identify mediators of
      granulocyte recruitment to the corneal stroma, we determined the relative
      contribution of chemokine receptors CXC chemokine receptor (CXCR)-2 (IL-8R
      homologue) and CCR1 using a murine model of ocular onchocerciasis (river
      blindness) in which neutrophils and eosinophils migrate from peripheral vessels
      to the central cornea. CXCR2(-/-) and CCR1(-/-) mice were immunized s.c. and
      injected into the corneal stroma with Ags from the parasitic helminth Onchocerca
      volvulus. We found that production of macrophage-inflammatory protein (MIP)-2,
      KC, and MIP-1 alpha was localized to the corneal stroma, rather than to the
      epithelium, which was consistent with the location of neutrophils in the cornea.
      CCR1 deficiency did not inhibit neutrophil or eosinophil infiltration to the
      cornea or development of corneal opacification. In marked contrast, neutrophil
      recruitment to the corneas of CXCR2(-/-) mice was significantly impaired (p <
      0.0001 compared with control, BALB/c mice) with only occasional neutrophils
      detected in the central cornea. Furthermore, CXCR2(-/-) mice developed only mild
      corneal opacification compared with BALB/c mice. These differences were not due
      to impaired KC and MIP-2 production in the corneal stroma of CXCR2(-/-) mice,
      which was similar to BALB/c mice. Furthermore, although MIP-1 alpha production
      was lower in CXCR2(-/-) mice than BALB/c mice, eosinophil recruitment to the
      cornea was not impaired. These observations demonstrate the critical role for
      CXCR2 expression in neutrophil infiltration to the cornea and may indicate a
      target for immune intervention in neutrophil-mediated corneal inflammation.

PMID- 11238652
TI  - Early response cytokines and innate immunity: essential roles for TNF receptor 1
      and type I IL-1 receptor during Escherichia coli pneumonia in mice.
AB  - The early response cytokines, TNF and IL-1, have overlapping biologic effects
      that may function to propagate, amplify, and coordinate host responses to
      microbial challenges. To determine whether signaling from these early response
      cytokines is essential to orchestrating innate immune responses to intrapulmonary
      bacteria, the early inflammatory events induced by instillation of Escherichia
      coli into the lungs were compared in wild-type (WT) mice and mice deficient in
      both TNF receptor 1 (TNFR1) and the type I IL-1 receptor (IL1R1). Neutrophil
      emigration and edema accumulation induced by E. coli were significantly
      compromised by TNFR1/IL1R1 deficiency. Neutrophil numbers in the circulation and
      within alveolar septae did not differ between WT and TNFR1/IL1R1 mice, suggesting
      that decreased neutrophil emigration did not result from decreased sequestration
      or delivery of intravascular neutrophils. The nuclear translocation of NF-kappa B
      and the expression of the chemokine macrophage inflammatory protein-2 did not
      differ between WT and TNFR1/IL1R1 lungs. However, the concentration of the
      chemokine KC was significantly decreased in the bronchoalveolar lavage fluids of
      TNFR1/IL1R1 mice compared with that in WT mice. Thus, while many of the molecular
      and cellular responses to E. coli in the lungs did not require signaling by
      either TNFR1 or IL1R1, early response cytokine signaling was critical to KC
      expression in the pulmonary air spaces and neutrophil emigration from the
      alveolar septae.

PMID- 11238653
TI  - CD8 CTL from genital herpes simplex lesions: recognition of viral tegument and
      immediate early proteins and lysis of infected cutaneous cells.
AB  - HSV-2 causes chronic infections. CD8 CTL may play several protective roles, and
      stimulation of a CD8 response is a rational element of vaccine design for this
      pathogen. The viral Ags recognized by CD8 T cells are largely unknown. It has
      been hypothesized that HSV inhibition of TAP may favor recognition of virion
      input proteins or viral immediate early proteins. We tested this prediction using
      HSV-specific CD8 CTL clones obtained from genital HSV-2 lesions. Drug and
      replication block experiments were consistent with specificity for the above
      named classes of viral proteins. Fine specificity was determined by expression
      cloning using molecular libraries of viral DNA, and peptide epitopes recognized
      at nanomolar concentrations were identified. Three of four clones recognized the
      viral tegument proteins encoded by genes UL47 and UL49. These proteins are
      transferred into the cytoplasm on virus entry. Processing of the tegument Ag
      derived epitopes was TAP dependent. The tegument-specific CTL were able to lyse
      HLA class I-appropriate fibroblasts after short times of infection. Lysis of
      keratinocytes required longer infection and pretreatment with IFN-gamma. Another
      clone recognized an immediate early protein, ICP0. Lymphocytes specific for these
      lesion-defined epitopes could be reactivated from the PBMC of additional
      subjects. These data are consistent with an influence of HSV immune evasion genes
      upon the selection of proteins recognized by CD8 CTL in lesions. Tegument
      proteins, identified for the first time as Ags recognized by HSV-specific CD8
      CTL, are rational candidate vaccine compounds.

PMID- 11238654
TI  - Mice lacking the multidrug resistance protein 1 are resistant to Streptococcus
      pneumoniae-induced pneumonia.
AB  - Leukotrienes (LTs) are considered important for antibacterial defense in the
      lung. Multidrug resistance protein 1 (mrp1) is a transmembrane protein
      responsible for the cellular extrusion of LTC(4). To determine the role of mrp1
      in host defense against pneumonia, mrp1(-/-) and wild-type mice were intranasally
      inoculated with Streptococcus pneumoniae. mrp1(-/-) mice displayed a diminished
      outgrowth of pneumococci in lungs and a strongly reduced mortality. These
      findings were related to an effect of mrp1 on LT metabolism, because survival was
      similar in mrp1(-/-) and wild-type mice treated with the 5-lipoxygenase
      activating protein inhibitor MK-886. Although LTC(4) levels remained low in the
      bronchoalveolar lavage fluid of mrp1(-/-) mice, LTB(4) concentrations were higher
      than in wild-type mice. These elevated LTB(4) concentrations were important for
      the relative protection of mrp1(-/-) mice, because the LTB(4) antagonist LTB(4)
      dimethyl amide abolished their survival advantage. In vitro experiments suggested
      that the intracellullar accumulation of LTC(4) in mrp1(-/-) mice results in
      product inhibition of LTC(4)-synthase, diminishing substrate competition between
      LTA(4)-hydrolase (which yields LTB(4)) and LTC(4)-synthase for the available
      LTA(4). We conclude that mrp1(-/-) mice are resistant against pneumococcal
      pneumonia by a mechanism that involves increased release of LTB(4). These results
      identify mrp1 as a novel target for adjunctive therapy in pneumonia.

PMID- 11238655
TI  - Intestinal and splenic T cell responses to enteric Listeria monocytogenes
      infection: distinct repertoires of responding CD8 T lymphocytes.
AB  - Listeria monocytogenes is an intracellular bacterium that causes systemic
      infections after traversing the intestinal mucosa. Clearance of infection and
      long term protective immunity are mediated by L. monocytogenes-specific CD8 T
      lymphocytes. In this report, we characterize the murine CD8 T cell response in
      the lamina propria and intestinal epithelium after enteric L. monocytogenes
      infection. We find that the frequency of MHC class Ia-restricted, L.
      monocytogenes-specific T cells is approximately 4- to 5-fold greater in the
      lamina propria than in the spleen of mice after oral or i.v. infection. Although
      the kinetics of T cell expansion and contraction are similar in spleen, lamina
      propria, and intestinal epithelium, high frequencies of Ag-specific T cells are
      detected only in the lamina propria 1 mo after infection. In contrast to MHC
      class Ia-restricted T cells, the frequency of H2-M3-restricted, L. monocytogenes
      specific T cells is decreased in the intestinal mucosa relative to that found in
      the spleen. In addition to this disparity, we find that MHC class Ia-restricted
      CD8 T cells specific for a dominant L. monocytogenes epitope have different TCR V
      beta repertoires in the spleen and intestinal mucosa of individual mice. These
      findings indicate that the intestinal mucosa is a depot where L. monocytogenes
      specific effector CD8 T cells accumulate during and after infection irrespective
      of immunization route. Furthermore, our results demonstrate that CD8 T cell
      populations in these two sites, although overlapping in Ag specificity, are
      distinct in terms of their repertoire.

PMID- 11238656
TI  - Differential effects of a Toll-like receptor antagonist on Mycobacterium
      tuberculosis-induced macrophage responses.
AB  - We previously showed that viable Mycobacterium tuberculosis (Mtb) bacilli contain
      distinct ligands that activate cells via the mammalian Toll-like receptor (TLR)
      proteins TLR2 and TLR4. We now demonstrate that expression of a dominant negative
      TLR2 or TLR4 proteins in RAW 264.7 macrophages partially blocked Mtb-induced NF
      kappa B activation. Coexpression of both dominant negative proteins blocked
      virtually all Mtb-induced NF-kappa B activation. The role of the TLR4 coreceptor
      MD-2 was also examined. Unlike LPS, Mtb-induced macrophage activation was not
      augmented by overexpression of ectopic MD-2. Moreover, cells expressing an LPS
      unresponsive MD-2 mutant responded normally to Mtb. We also observed that the
      lipid A-like antagonist E5531 specifically inhibited TLR4-dependent Mtb-induced
      cellular responses. E5531 could substantially block LPS- and Mtb-induced TNF
      alpha production in both RAW 264.7 cells and primary human alveolar macrophages
      (AM phi). E5531 inhibited Mtb-induced AM phi apoptosis in vitro, an effect that
      was a consequence of the inhibition of TNF-alpha production by E5531. In
      contrast, E5531 did not inhibit Mtb-induced NO production in RAW 264.7 cells and
      AM phi. Mtb-stimulated peritoneal macrophages from TLR2- and TLR4-deficient
      animals produced similar amounts of NO compared with control animals,
      demonstrating that these TLR proteins are not required for Mtb-induced NO
      production. Lastly, we demonstrated that a dominant negative MyD88 mutant could
      block Mtb-induced activation of the TNF-alpha promoter, but not the inducible NO
      synthase promoter, in murine macrophages. Together, these data suggest that Mtb
      induced TNF-alpha production is largely dependent on TLR signaling. In contrast,
      Mtb-induced NO production may be either TLR independent or mediated by TLR
      proteins in a MyD88-independent manner.

PMID- 11238657
TI  - Histamine induces exocytosis and IL-6 production from human lung macrophages
      through interaction with H1 receptors.
AB  - Increasing evidence suggests that a continuous release of histamine from mast
      cells occurs in the airways of asthmatic patients and that histamine may modulate
      functions of other inflammatory cells such as macrophages. In the present study
      histamine (10(-9)-10(-6) M) increased in a concentration-dependent fashion the
      basal release of beta-glucuronidase (EC(50) = 8.2 +/- 3.5 x 10(-9) M) and IL-6
      (EC(50) = 9.3 +/- 2.9 x 10(-8) M) from human lung macrophages. Enhancement of
      beta-glucuronidase release induced by histamine was evident after 30 min and
      peaked at 90 min, whereas that of IL-6 required 2-6 h of incubation. These
      effects were reproduced by the H(1) agonist (6-[2-(4-imidazolyl)ethylamino]-N-(4
      trifluoromethylphenyl)heptane carboxamide but not by the H(2) agonist dimaprit.
      Furthermore, histamine induced a concentration-dependent increase of
      intracellular Ca(2+) concentrations ([Ca(2+)](i)) that followed three types of
      response, one characterized by a rapid increase, a second in which [Ca(2+)](i)
      displays a slow but progressive increase, and a third characterized by an
      oscillatory pattern. Histamine-induced beta-glucuronidase and IL-6 release and
      [Ca(2+)](i) elevation were inhibited by the selective H(1) antagonist
      fexofenadine (10(-7)-10(-4) M), but not by the H(2) antagonist ranitidine.
      Inhibition of histamine-induced beta-glucuronidase and IL-6 release by
      fexofenadine was concentration dependent and displayed the characteristics of a
      competitive antagonism (K(d) = 89 nM). These data demonstrate that histamine
      induces exocytosis and IL-6 production from human macrophages by activating H(1)
      receptor and by increasing [Ca(2+)](i) and they suggest that histamine may play a
      relevant role in the long-term sustainment of allergic inflammation in the
      airways.

PMID- 11238658
TI  - Differential regulation of formyl peptide receptor-like 1 expression during the
      differentiation of monocytes to dendritic cells and macrophages.
AB  - Monocytes are the common precursors for myeloid dendritic cells (DC) and
      macrophages. Identification of chemotactic receptors expressed by myeloid DC,
      macrophages, and their precursors in the course of differentiation and maturation
      is important not only for elucidation of their in vivo trafficking, but also for
      understanding of the functional distinction between DC and macrophages. We chose
      to study formyl peptide receptor like-1 (FPRL1), a chemotactic receptor known to
      interact with several endogenous agonists that are involved in inflammatory and
      host defense responses. Here we show that FPRL1 is down-regulated as monocytes
      differentiate into DC. This down-regulation occurs at both mRNA and functional
      levels. Therefore, the interaction of FPRL1 with its agonists is more likely to
      regulate the in vivo trafficking of DC precursors than DC. In contrast, FPRL1
      expression is maintained at both mRNA and functional levels as monocytes
      differentiate into macrophages. Thus, our results demonstrate further
      distinctions between myeloid DC and macrophages, albeit they share a common
      precursor. The fact that macrophages rather than myeloid DC express functional
      FPRL1 suggests that this chemotactic receptor may be more involved in
      inflammatory reactions and innate host defense than in adaptive immune responses.

PMID- 11238659
TI  - Differential roles of the NPXXY motif in formyl peptide receptor signaling.
AB  - The NPXXY motif (X represents any amino acid) in the seventh transmembrane domain
      of the chemotactic formyl peptide receptor (FPR) is highly conserved among G
      protein-coupled receptors. Recent work suggested that this motif contributes to G
      protein-coupled receptor internalization and signal transduction; however, its
      role in FPR signaling remains unclear. In this study we replaced Asn(297) and
      Tyr(301) in the NPXXY motif of the human FPR with Ala (N297A) and Ala/Phe
      (Y301A/Y301F), respectively, and determined the effects of the substitutions on
      FPR functions in transfected rat basophilic leukemia cells. Whereas all the
      mutant receptors were expressed on the cell surface, the N297A receptor exhibited
      reduced binding affinity and was unable to mediate activation of phospholipase C
      beta and the p42/44 mitogen-activated protein kinase (MAP kinase). The Y301F
      receptor displayed significantly decreased ligand-stimulated internalization and
      MAP kinase activation, suggesting that the hydrogen bonding at Tyr(301) is
      critical for these functions. The Y301F receptor showed a chemotactic response
      similar to that of wild-type FPR, indicating that cell chemotaxis does not
      require receptor internalization and hydrogen bonding at the Tyr(301) position.
      In contrast, the Y301A receptor displayed a left-shifted, but overall reduced,
      chemotaxis response that peaked at 0.1-1 nM. Finally, using a specific MAP kinase
      kinase inhibitor, we found that activation of MAP kinase is required for
      efficient FPR internalization, but is not essential for chemotaxis. These
      findings demonstrate that residues within the NPXXY motif differentially regulate
      the functions of FPR.

PMID- 11238660
TI  - Effect of redox modulation on xenogeneic target cells: the combination of nitric
      oxide and thiol deprivation protects porcine endothelial cells from lysis by IL-2
      activated human NK cells.
AB  - Evidence suggests that NK cells contribute to the pathogenesis of delayed
      rejection of vascularized xenografts, and NK cells have been suggested to
      participate in hyperacute xenograft rejection. Endothelial cells have been shown
      to be the primary target of the recipient's immune responses that mediate both
      hyperacute and delayed xenograft rejection. Under conditions of oxidative stress
      induced by thiol deprivation, but not under normal conditions, pretreatment of
      porcine aortic endothelial cells (PAECs) with the NO donor, S-nitroso-N-acetyl
      penicillamine, dramatically inhibited killing of PAEC target cells by IL-2
      activated human NK cells. This same combined treatment reduced both surface
      expression and mRNA levels of E-selectin. Moreover, anti-E-selectin mAb, but not
      Ab to VCAM-1, protected PAEC from lysis by human IL-2-activated NK cells in a
      dose-dependent manner. These findings suggest that expression of porcine E
      selectin is important for the cytotoxicity of PAEC mediated by activated human NK
      cells and may be involved in the redox-mediated modulation of that cytotoxicity.
      It is known that NF-kappa B activation is required for transcription of E
      selectin, and the current data show that the suppression of E-selectin expression
      by S-nitroso-N-acetyl-penicillamine pretreatment and thiol deprivation was
      associated with reduced NF-kappa B DNA-binding activity in PAEC. These data
      suggest that the regulation of porcine E-selectin may be important for modulating
      delayed xenograft rejection and that manipulation of cellular redox systems may
      provide a means to protect xenogeneic endothelial cells from NK cell-mediated
      cytotoxicity.

PMID- 11238661
TI  - Resting murine neutrophils express functional alpha 4 integrins that signal
      through Src family kinases.
AB  - There is mounting evidence that alpha(4) (CD49d) integrins are involved in
      neutrophil recruitment and function during inflammatory responses. We report that
      all resting murine neutrophils derived from bone marrow or peripheral blood
      express easily detectable levels of alpha(4) integrins on their surface. These
      alpha(4) integrins were functional, as demonstrated by stimulation of respiratory
      burst when neutrophils adhered to surfaces coated with the murine vascular cell
      adhesion molecule-1 (mVCAM-1). Adhesion occurred via alpha(4) integrins, as
      preincubation of neutrophils with an anti-alpha(4)-specific Ab inhibited
      attachment to mVCAM-1. Direct cross-linking of the alpha(4) integrin subunit by
      surface-bound mAbs also elicited superoxide release and release of the secondary
      granule marker, lactoferrin. The functional responses that occurred downstream of
      alpha(4) integrin cross-linking required signaling by Src family kinases.
      Neutrophils derived from hck(-/-)fgr(-/-)lyn(-/-) triple-knockout or hck(-/-)fgr(
      /-) double-knockout mice failed to undergo respiratory burst when plated on mVCAM
      1. Triple mutant neutrophils were also defective in release of both superoxide
      and lactoferrin when plated on surfaces coated with mAbs directed against
      alpha(4). Correlated with impaired alpha(4)-induced functional responses, triple
      mutant neutrophils also failed to spread and tightly adhere to anti-alpha(4) mAb
      coated surfaces. This is the first direct evidence that functional alpha(4)
      integrins are expressed by murine PMNs, and that these surface molecules can
      mediate cellular responses such as tight adhesion, spreading, sustained
      respiratory burst, and specific granule release in vitro. Moreover the alpha(4)
      integrins, like all other integrins tested, use the Src family kinases to
      transduce intracellular signals.

PMID- 11238662
TI  - Different therapeutic outcomes in experimental allergic encephalomyelitis
      dependent upon the mode of delivery of IL-10: a comparison of the effects of
      protein, adenoviral or retroviral IL-10 delivery into the central nervous system.
AB  - Experimental allergic encephalomyelitis (EAE) is a CNS autoimmune disease
      mediated by the action of CD4(+) T cells, macrophages, and proinflammatory
      cytokines. IL-10 is a cytokine shown to have many anti-inflammatory properties.
      Studies have shown both inhibition and exacerbation of EAE after systemic IL-10
      protein administration. We have compared the inhibitory effect in EAE of Il10
      gene delivery in the CNS. Fibroblasts transduced with retroviral vectors
      expressing IL-10 could inhibit EAE. This was not associated with a prevention of
      cellular recruitment but an alteration in their phenotype, notably an increase in
      the numbers of CD8(+) T and B cells. In marked contrast, CNS delivery of
      adenovirus coding for mouse IL-10 or IL-10 protein performed over a wide dose
      range failed to inhibit disease, despite producing similar or greater amounts of
      IL-10 protein. Thus the action of IL-10 may differ depending on the local
      cytokine microenvironment produced by the gene-secreting cell types.

PMID- 11238663
TI  - The cutaneous response in humans to Treponema pallidum lipoprotein analogues
      involves cellular elements of both innate and adaptive immunity.
AB  - To extend prior studies implicating treponemal lipoproteins as major
      proinflammatory agonists of syphilitic infection, we examined the responses
      induced by intradermal injection of human subjects with synthetic lipoprotein
      analogues (lipopeptides) corresponding to the N termini of the 17- and 47-kDa
      lipoproteins of Treponema pallidum. Responses were assessed visually and by flow
      cytometric analysis of dermal leukocyte populations within fluids aspirated from
      suction blisters raised over the injection sites. Lipopeptides elicited dose
      dependent increases in erythema/induration and cellular infiltrates. Compared
      with peripheral blood, blister fluids were highly enriched for
      monocytes/macrophages, cutaneous lymphocyte Ag-positive memory T cells, and
      dendritic cells. PB and blister fluids contained highly similar ratios of CD123(
      )/CD11c(+) (DC1) and CD123(+)/CD11c(-) (DC2) dendritic cells. Staining for
      maturation/differentiation markers (CD83, CD1a) and costimulatory molecules
      (CD80/CD86) revealed that blister fluid DC1, but not DC2, cells were more
      developmentally advanced than their peripheral blood counterparts. Of particular
      relevance to the ability of syphilitic lesions to facilitate the transmission of
      M-tropic strains of HIV-1 was a marked enhancement of CCR5 positivity among
      mononuclear cells in the blister fluids. Treponemal lipopeptides have the
      capacity to induce an inflammatory milieu reminiscent of that found in early
      syphilis lesions. In contrast with in vitro studies, which have focused upon the
      ability of these agonists to stimulate isolated innate immune effector cells, in
      this study we show that in a complex tissue environment these molecules have the
      capacity to recruit cellular elements representing the adaptive as well as the
      innate arm of the cellular immune response.

PMID- 11238664
TI  - Functional IL-2 receptor beta (CD122) and gamma (CD132) chains are expressed by
      fibroblast-like synoviocytes: activation by IL-2 stimulates monocyte
      chemoattractant protein-1 production.
AB  - The expression of the IL-2R alpha-, beta-, and gamma-chains, CD25, CD122, and
      CD132, respectively, was investigated on fibroblast-like synoviocytes (FLS) and
      dermal fibroblasts (DF). Both protein and mRNA for CD122 and CD132 were observed
      but there was no evidence of CD25 expression. Quantification of the Ag binding
      sites for CD122 showed that FLS expressed 4 times more receptor molecules than
      DF. The functional capability of these receptors was confirmed by the production
      of monocyte chemoattractant protein-1 (MCP-1) in direct response to stimulation
      by IL-2, which could be inhibited by neutralizing anti-CD122 mAb. Both rheumatoid
      arthritis (RA) and osteoarthritis (OA) FLS and DF spontaneously produced MCP-1 in
      culture over a similar range of concentrations. However, RA and OA FLS produced
      significantly greater levels of MCP-1 following stimulation by IL-2 and IL-1
      beta; RA FLS produced significantly more MCP-1 than OA FLS. Addition of exogenous
      IL-2 caused a slight, but significant, decrease in MCP-1 production by DF. The
      addition of neutralizing anti-CD122 mAb to FLS cultures partially, but
      significantly, reduced the IL-2-induced MCP-1 secretion, but did not effect
      either the spontaneous or IL-1 beta-induced secretion of MCP-1. Increased
      tyrosine phosphorylation was observed in FLS lysates following 30-min incubation
      with IL-2. In conclusion, in the inflamed synovium, as activated T cells migrate
      through the sublining and lining layer, T cell-derived IL-2 may activate FLS to
      secrete MCP-1, thus recruiting macrophages into the rheumatoid synovium and
      perpetuating inflammation.

PMID- 11238665
TI  - A keratin peptide inhibits mannose-binding lectin.
AB  - Complement plays a significant role in mediating endothelial injury following
      oxidative stress. We have previously demonstrated that the lectin complement
      pathway (LCP), which is initiated by deposition of the mannose-binding lectin
      (MBL), is largely responsible for activating complement on endothelial cells
      following periods of oxidative stress. Identifying functional inhibitors that
      block MBL binding will be useful in characterizing the role of the LCP in disease
      models. The human cytokeratin peptide SFGSGFGGGY has been identified as a
      molecular mimic of N-acetyl-D-glucosamine (GlcNAc), a known ligand of MBL. Thus,
      we hypothesized that this peptide would specifically bind to MBL and functionally
      inhibit the LCP on endothelial cells following oxidative stress. Using a BIAcore
      3000 optical biosensor, competition experiments were performed to demonstrate
      that the peptide SFGSGFGGGY inhibits binding of purified recombinant human MBL to
      GlcNAc in a concentration-dependent manner. Solution affinity data generated by
      BIAcore indicate this peptide binds to MBL with an affinity (K(D)) of 5 x 10(-5)
      mol/L. Pretreatment of human serum (30%) with the GlcNAc-mimicking peptide (10-50
      microg/ml) significantly attenuated MBL and C3 deposition on human endothelial
      cells subjected to oxidative stress in a dose-dependent manner, as demonstrated
      by cell surface ELISA and confocal microscopy. Additionally, this decapeptide
      sequence attenuated complement-dependent VCAM-1 expression following oxidative
      stress. These data indicate that a short peptide sequence that mimics GlcNAc can
      specifically bind to MBL and functionally inhibit the proinflammatory action of
      the LCP on oxidatively stressed endothelial cells.

PMID- 11238666
TI  - Neuronal expression of a functional receptor for the C5a complement activation
      fragment.
AB  - The present studies were undertaken to determine whether neuronal subsets in
      normal brains constitutively express functionally competent C5a receptors. In
      situ hybridization studies coupled with immunohistochemical approaches revealed
      that most neurons in the hippocampal formation, many pyramidal cortical neurons,
      and cerebellar Purkinje neurons in normal human and murine brains constitutively
      express C5a receptors. Neuronal C5a receptors bound C5a-coated fluorescent
      microspheres, and primary rodent hippocampal neurons responded to C5a with
      increased calcium fluxes via a pertussis-sensitive, presumably Gi-coupled
      protein. Additional studies with human neuroblastoma cells conducted to address
      the functional role of C5a receptors revealed that C5a triggered rapid activation
      of protein kinase C and activation and nuclear translocation of the NF-kappa B
      transcription factor. In addition, C5a was found to be mitogenic for
      undifferentiated human neuroblastoma cells, a novel action for the C5aR. In
      contrast, C5a protected terminally differentiated human neuroblastoma cells from
      toxicity mediated by the amyloid A beta peptide. Thus, normal rodent hippocampal
      neurons as well as undifferentiated and differentiated human neuroblastoma cells
      express functional C5a receptors. These results have implications for
      understanding the role of neuronal C5aR receptors in normal neuronal development,
      neuronal homeostasis, and neuroinflammatory conditions such as Alzheimer's
      disease.

PMID- 11238667
TI  - Redirection of T cell effector function in vivo and enhanced collagen-induced
      arthritis mediated by an IL-2R beta/IL-4R alpha chimeric cytokine receptor
      transgene.
AB  - Chronic inflammatory autoimmune diseases such as diabetes, experimental
      autoimmune encephalomyelitis, and collagen-induced arthritis (CIA) are associated
      with type 1 (Th1, Tc1) T cell-dependent responses against autoantigens. Immune
      deviation toward type 2 (Th2, Tc2) response has been proposed as a potential
      means of gene therapy or immunomodulation to treat autoimmune diseases based on
      evidence that type 2 cytokines can prevent or alleviate these conditions. In this
      report we assessed the effects of elevated type 2 responses on CIA using
      transgenic mice expressing an IL-2R beta/IL-4R alpha chimeric cytokine receptor
      transgene specifically in T cells. In response to IL-2 binding, this chimeric
      receptor transduces IL-4-specific signals and dramatically enhances type 2
      responses. In contrast to published reports of Th2-mediated protection, CIA was
      exacerbated in IL-2R beta/IL-4R alpha chimeric receptor transgenic mice, with
      increased disease incidence, severity, and earlier disease onset. The aggravated
      disease in transgenic mice was associated with an increase in type 2 cytokines
      (IL-4, IL-5, IL-10) and an increase in collagen-specific IgG1 levels. However,
      IFN-gamma production is not affected significantly in the induction phase of the
      disease. There is also an extensive eosinophilic infiltration in the arthritic
      joints of the transgenic animal, suggesting a direct contribution of type 2
      response to joint inflammation. Taken together, our findings provide novel
      evidence that enhancement of a polyclonal type 2 response in immunocompetent
      hosts may exacerbate an autoimmune disease such as CIA, rather than serving a
      protective role. This finding raises significant caution with regard to the
      potential use of therapeutic approaches based on immune deviation toward type 2
      responses.

PMID- 11238668
TI  - Molecular dissection of the tissue transglutaminase autoantibody response in
      celiac disease.
AB  - Celiac disease (CD) is an intestinal malabsorption characterized by intolerance
      to cereal proteins accompanied by immunological responses to dietary gliadins and
      tissue transglutaminase, an autoantigen located in the endomysium. Tissue
      transglutaminase belongs to the family of enzymes that catalyze protein cross
      linking reactions and is constitutively expressed in many tissues as well as
      being activated during apoptosis. The role of gliadins in eliciting the immune
      response in CD and how transglutaminase is linked to the primary reaction are
      still unclear. In this work, we report the production and analysis of six phage
      Ab libraries from the peripheral and intestinal lymphocytes of three CD patients.
      We were able to isolate Abs to transglutaminase from all intestinal lymphocytes
      libraries but not from those obtained from peripheral lymphocytes. This is in
      contrast to Abs against gliadin, which could be obtained from all libraries,
      indicating that the humoral response against transglutaminase occurs at the local
      level, whereas that against gliadin occurs both peripherally and centrally. Abs
      from all three patients recognized the same transglutaminase epitopes with a bias
      toward the use of the V(H)5 Ab variable region family. The possible role of these
      anti-transglutaminase Abs in the onset of CD and associated autoimmune
      pathologies is discussed.

PMID- 11238669
TI  - The major synovial targets of the rheumatoid arthritis-specific antifilaggrin
      autoantibodies are deiminated forms of the alpha- and beta-chains of fibrin.
AB  - IgG antifilaggrin autoantibodies (AFA) are the most specific serological markers
      of rheumatoid arthritis. In epithelial tissues, they recognize citrulline-bearing
      epitopes present on various molecular forms of (pro)filaggrin. Histological
      analysis of rheumatoid synovial membranes with an Ab to citrulline showed
      labeling of interstitial amorphous deposits and mononuclear cells of various
      types. Immunochemical analysis of exhaustive sequential extracts of the same
      tissues showed that they contain several deiminated (citrulline containing)
      proteins. Among them, two proteins, p64--78 and p55--61, present in urea-DTT and
      guanidine extracts, were shown by immunoblotting to be specifically targeted by
      AFA. By amino-terminal sequencing the proteins were identified as deiminated
      forms of the alpha- and beta-chains of fibrin, respectively. Their identity was
      confirmed using several Abs specific for the A alpha- and/or to the B beta-chain
      of fibrin(ogen). Moreover, AFA-positive rheumatoid arthritis (RA) sera and
      purified AFA were highly reactive to the A alpha- and B beta-chains of human
      fibrinogen only after deimination of the molecules by a peptidylarginine
      deiminase. Autoantibodies affinity purified from a pool of RA sera onto
      deiminated fibrinogen were reactive toward all of the epithelial and synovial
      targets of AFA. This confirmed that the autoantibodies to the deiminated A alpha
      and B beta-chains of fibrinogen, the autoantibodies to the synovial proteins p64-
      78 and p55--61, and, lastly, AFA, constitute largely overlapping autoantibody
      populations. These results show that deiminated forms of fibrin deposited in the
      rheumatoid synovial membranes are the major target of AFA. They suggest that
      autoimmunization against deiminated fibrin is a critical step in RA pathogenesis.

PMID- 11238670
TI  - Carbon monoxide generated by heme oxygenase-1 suppresses the rejection of mouse
      to-rat cardiac transplants.
AB  - Mouse-to-rat cardiac transplants survive long term after transient complement
      depletion by cobra venom factor and T cell immunosuppression by cyclosporin A.
      Expression of heme oxygenase-1 (HO-1) by the graft vasculature is critical to
      achieve graft survival. In the present study, we asked whether this protective
      effect was attributable to the generation of one of the catabolic products of HO
      1, carbon monoxide (CO). Our present data suggests that this is the case. Under
      the same immunosuppressive regimen that allows mouse-to-rat cardiac transplants
      to survive long term (i.e., cobra venom factor plus cyclosporin A), inhibition of
      HO-1 activity by tin protoporphyrin, caused graft rejection in 3--7 days.
      Rejection was associated with widespread platelet sequestration, thrombosis of
      coronary arterioles, myocardial infarction, and apoptosis of endothelial cells as
      well as cardiac myocytes. Under inhibition of HO-1 activity by tin
      protoporphyrin, exogenous CO suppressed graft rejection and restored long-term
      graft survival. This effect of CO was associated with inhibition of platelet
      aggregation, thrombosis, myocardial infarction, and apoptosis. We also found that
      expression of HO-1 by endothelial cells in vitro inhibits platelet aggregation
      and protects endothelial cells from apoptosis. Both these actions of HO-1 are
      mediated through the generation of CO. These data suggests that HO-1 suppresses
      the rejection of mouse-to-rat cardiac transplants through a mechanism that
      involves the generation of CO. Presumably CO suppresses graft rejection by
      inhibiting platelet aggregation that facilitates vascular thrombosis and
      myocardial infarction. Additional mechanisms by which CO overcomes graft
      rejection may involve its ability to suppress endothelial cell apoptosis.

PMID- 11238671
TI  - Immune enhancing effect of a growth hormone secretagogue.
AB  - Growth hormone (GH) has been known to enhance immune responses, whether directly
      or through the insulin like growth factor-1, induced by GH. Recently a
      nonpeptidyl small m.w. compound, a GH secretagogue (GHS), was found to induce the
      production of GH by the pituitary gland. In this study, we examined the effect of
      GHS in immunological functions of 5- to 6-wk-old and 16- to 24-month-old mice. In
      young mice, we observed a significant increase in PBLs, but T and B cell
      proliferative responses were not consistently enhanced. The old mice, treated
      with GHS for 3 wk, did not show increases in peripheral lymphocytes, but they
      exhibited a statistically significant increase in thymic cellularity and
      differentiation. When inoculated with a transplantable lymphoma cell line, EL4,
      the treated old mice showed statistically significant resistance to the
      initiation of tumors and the subsequent metastases. Generation of CTL to EL4
      cells was also enhanced in the treated mice, suggesting that GHS has a
      considerable immune enhancing effect, particularly in the old mice. We have also
      found that GHS promoted better thymic engraftment in bone marrow transplant of
      SCID mice. We found more cycling cells in the spleens of treated mice, suggesting
      that GHS may exert its immune enhancing effect by promoting cell division in
      lymphoid cells. These observations ascribe to GHS a novel therapy possible for
      aging, AIDS, and transplant individuals, whose immune functions are compromised.

PMID- 11238672
TI  - Human monoclonal rheumatoid synovial B lymphocyte hybridoma with a new disease
      related specificity for cartilage oligomeric matrix protein.
AB  - Joint-specific self-Ags are considered to play an important role in the induction
      of synovial T and B cell expansion in human rheumatoid arthritis (RA). However,
      the nature of these autoantigens is still enigmatic. In this study a somatically
      mutated IgG2 lambda B cell hybridoma was established from the synovial membrane
      of an RA patient and analyzed for its Ag specificity. A heptameric peptide of
      cartilage oligomeric matrix protein (COMP) could be characterized as the target
      structure recognized by the human synovial B cell hybridoma. The clonotypic V(H)
      sequences of the COMP-specific hybridoma could also be detected in synovectomy
      material derived from five different RA patients but in none of the investigated
      osteoarthritis cases (n = 5), indicating a preferential usage of V(H) genes
      closely related to those coding for a COMP-specific Ag receptor in RA synovial B
      cells. Moreover, the COMP heptamer was preferentially recognized by circulating
      IgG in RA (n = 22) compared with osteoarthritis patients (n = 24) or age-matched
      healthy controls (n = 20; both p < 0.0001). Hence, the COMP-specific serum IgG is
      likely to reflect local immune responses toward a cartilage- and tendon
      restricted Ag that might be crucial to the induction of tissue damage in RA.

PMID- 11238673
TI  - Regulation of experimental autoimmune encephalomyelitis in the C57BL/6J mouse by
      NK1.1+, DX5+, alpha beta+ T cells.
AB  - C57BL/6 (B6) mice with targeted mutations of immune function genes were used to
      investigate the mechanism of recovery from experimental autoimmune
      encephalomyelitis (EAE). The acute phase of passive EAE in the B6 mouse is
      normally resolved by partial recovery followed by mild sporadic relapses. B6 TCR
      beta-chain knockout (KO) recipients of a myelin oligodendrocyte glycoprotein p35
      55 encephalitogenic T cell line failed to recover from the acute phase of passive
      EAE. In comparison with wild-type mice, active disease was more severe in beta(2)
      microglobulin KO mice. Reconstitution of TCR beta-chain KO mice with wild-type
      spleen cells halted progression of disease and favored recovery. Spleen cells
      from T cell-deficient mice, IL-7R KO mice, or IFN-gamma KO mice were ineffective
      in this regard. Irradiation or treatment of wild-type spleen cell population with
      anti-NK1.1 mAb before transfer abrogated the protective effect. Removal of DX5(+)
      cells from wild-type spleen cells by anti-DX5 Ab-coated magnetic beads before
      reconstitution abrogated the suppressive properties of the spleen cells. TCR
      deficient recipients of the enriched DX5(+) cell population recovered normally
      from passively induced acute disease. DX5(+) cells were sorted by FACS into
      DX5(+) alpha beta TCR(+) and DX5(+) alpha beta TCR(-) populations. Only
      recipients of the former recovered normally from clinical disease. These results
      indicate that recovery from acute EAE is an active process that requires
      NK1.1(+), DX5(+) alpha beta(+) TCR spleen cells and IFN-gamma.

PMID- 11238674
TI  - Molecular basis of deficient IL-2 production in T cells from patients with
      systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease
      characterized by diverse cellular and biochemical aberrations, including
      decreased production of IL-2. Here we show that nuclear extracts from
      unstimulated SLE T cells, unlike extracts from normal T cells, express increased
      amounts of phosphorylated cAMP-responsive element modulator (p-CREM) that binds
      the -180 site of the IL-2 promoter. Nuclear extracts from stimulated normal T
      cells display increased binding of phosphorylated cAMP-responsive element binding
      protein (p-CREB) to the -180 site of the IL-2 promoter, whereas nuclear extracts
      from stimulated SLE T cells display primarily p-CREM and decreased p-CREB
      binding. In SLE T cells, p-CREM bound to the transcriptional coactivators, CREB
      binding protein and p300. Increased expression of p-CREM correlated with
      decreased production of IL-2. The transcription of a reporter gene driven by the 
      180 site was enhanced in normal T cells, but was suppressed in SLE T cells. These
      experiments demonstrate that transcriptional repression is responsible for the
      decreased production of IL-2 by SLE T cells.

PMID- 11238675
TI  - Identification of a matrix-degrading phenotype in human tuberculosis in vitro and
      in vivo.
AB  - Tuberculous meningitis is characterized by cerebral tissue destruction.
      Monocytes, pivotal in immune responses to Mycobacterium tuberculosis, secrete
      matrix metalloproteinase-9 (MMP-9), which facilitates leukocyte migration across
      the blood-brain barrier, but may cause cerebral injury. In vitro, human monocytic
      (THP-1) cells infected by live, virulent M. tuberculosis secreted MMP-9 in a dose
      dependent manner. At 24 h, MMP-9 concentrations increased 10-fold to 239 +/- 75
      ng/ml (p = 0.001 vs controls). MMP-9 mRNA became detectable at 24--48 h. In
      contrast, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) gene expression
      and secretion were similar to constitutive levels from controls at 24 h and
      increased just 5-fold by 48 h. In vivo investigation revealed MMP-9 concentration
      per leukocyte in cerebrospinal fluid (CSF) from tuberculous meningitis patients
      (n = 23; median (range), 3.19 (0.19--31.00) ng/ml/cell) to be higher than that in
      bacterial (n = 12; 0.23 (0.01--18.37) ng/ml/cell) or viral meningitis (n = 20;
      0.20 (0.04--31.00) ng/ml/cell; p < 0.01). TIMP-1, which was constitutively
      secreted into CSF, was not elevated in tuberculous compared with bacterial
      meningitis or controls. Thus, a phenotype in which MMP-9 activity is relatively
      unrestricted by TIMP-1 developed both in vitro and in vivo. This is functionally
      significant, since MMP-9 concentrations per CSF leukocyte (but not TIMP-1
      concentrations) were elevated in fatal tuberculous meningitis and in patients
      with signs of cerebral tissue damage (unconsciousness, confusion, or neurological
      deficit; p < 0.05). However, MMP-9 activity was unrelated to the severity of
      systemic illness. In summary, M. tuberculosis-infected monocytic cells develop a
      matrix-degrading phenotype, which was observed in vivo and relates to clinical
      signs reflecting cerebral injury in tuberculous meningitis.

PMID- 11238676
TI  - A milk protein lactoferrin enhances human T cell leukemia virus type I and
      suppresses HIV-1 infection.
AB  - Human T cell leukemia virus type I (HTLV-I) and HIV-1, causative agents of adult
      T cell leukemia/lymphoma and AIDS, respectively, are transmitted vertically via
      breast milk. Here we demonstrate that lactoferrin, a milk protein that has a
      variety of antimicrobial and immunomodulatory activities, facilitates replication
      of HTLV-I in lymphocytes derived from asymptomatic HTLV-I carriers and
      transmission to cord blood lymphocytes in vitro. Transient expression assays
      revealed that lactoferrin can transactivate HTLV-I long terminal repeat promoter.
      In contrast, lactoferrin inhibits HIV-1 replication, at least in part, at the
      level of viral fusion/entry. These results suggest that lactoferrin may have
      different effects on vertical transmission of the two milk-borne retroviruses.

PMID- 11238677
TI  - Environmental modulation of autoimmune arthritis involves the spontaneous
      microbial induction of T cell responses to regulatory determinants within heat
      shock protein 65.
AB  - Both genetic and environmental factors are believed to be involved in the
      induction of autoimmune diseases. Adjuvant arthritis (AA) is inducible in
      susceptible rat strains by injection of Mycobacterium tuberculosis, and arthritic
      rats raise T cell responses to the 65-kDa mycobacterial heat-shock protein
      (Bhsp65). We observed that Fischer 344 (F344) rats raised in a barrier facility
      (BF-F344) are susceptible to AA, whereas F344 rats maintained in a conventional
      facility (CV-F344) show significantly reduced incidence and severity of AA,
      despite responding well to the arthritogenic determinant within Bhsp65. The
      acquisition of protection from AA can be circumvented if rats are maintained on
      neomycin/acidified water. Strikingly, naive unimmunized CV-F344 rats but not BF
      F344 rats raised T cell responses to Bhsp65 C-terminal determinants (BCTD) (we
      have previously shown that BCTD are involved in regulation of acute AA in the
      Lewis rat); however, T cells of naive CV-F344 and BF-F344 gave a comparable level
      of proliferative response to a mitogen, but no response at all to an irrelevant
      Ag. Furthermore, adoptive transfer into naive BF-F344 rats of splenic cells of
      naive CV-F344 rats (restimulated with BCTD in vitro) before induction of AA
      resulted in a considerably reduced severity of AA. These results suggest that
      spontaneous (inadvertent) priming of BCTD-reactive T cells, owing to determinant
      mimicry between Bhsp65 and its homologues in microbial agents in the conventional
      environment, is involved in modulating the severity of AA in CV-F344 rats. These
      results have important implications in broadening understanding of the host
      microbe interaction in human autoimmune diseases.

PMID- 11238678
TI  - Opposite effects of IL-10 on the ability of dendritic cells and macrophages to
      replicate primary CXCR4-dependent HIV-1 strains.
AB  - We investigated the effect of IL-10 on replication of primary CXCR4-dependent
      (X4) HIV-1 strains by monocyte-derived dendritic cells (DCs) and macrophages (M
      Phis). M Phis efficiently replicated CXCR4-dependent HIV-1 (X4 HIV-1) strains NDK
      and VN44, whereas low levels of p24 were detected in supernatants of infected
      DCs. IL-10 significantly increased X4 HIV-1 replication by DCs but blocked viral
      production by M Phis as determined by p24 levels and semiquantitative nested PCR.
      IL-10 up-regulated CXCR4 mRNA and protein expression on DCs and M Phis,
      suggesting that IL-10 enhances virus entry in DCs but blocks an entry and/or
      postentry step in M Phis. The effect of IL-10 on the ability of DCs and M Phis to
      transmit virus to autologous CD4(+) T lymphocytes was investigated in coculture
      experiments. DCs exhibited a greater ability than did M Phis to transmit a
      vigorous infection to CD4(+) T cells despite their very low replication capacity.
      IL-10 had no effect on HIV-1 replication in DC:T cell cocultures but markedly
      decreased viral production in M Phi:T cell cocultures. These results demonstrate
      that IL-10 has opposite effects on the replication of primary X4 HIV-1 strains by
      DCs and M Phis. IL-10 increases X4-HIV-1 replication in DCs but does not alter
      their capacity to transmit virus to CD4(+) T lymphocytes. These findings suggest
      that increased levels of IL-10 observed in HIV-1-infected patients with disease
      progression may favor the replication of X4 HIV-1 strains in vivo.

PMID- 11238679
TI  - Dendritic cells injected via different routes induce immunity in cancer patients.
AB  - Dendritic cells (DC) represent potent APCs that are capable of generating tumor
      specific immunity. We performed a pilot clinical trial using Ag-pulsed DC as a
      tumor vaccine. Twenty-one patients with metastatic prostate cancer received two
      monthly injections of DC enriched and activated from their PBMC. DC were
      cocultured ex vivo with recombinant mouse prostatic acid phosphatase as the
      target neoantigen. Following enrichment, DC developed an activated phenotype with
      up-regulation of CD80, CD86, and CD83 expression. During culture, the DC
      maintained their levels of various adhesion molecules, including CD44, LFA-1,
      cutaneous lymphocyte-associated Ag, and CD49d, up-regulated CCR7, but lost CD62
      ligand and CCR5. In the absence of CD62 ligand, such cells would not be expected
      to prime T cells efficiently if administered i.v. due to their inability to
      access lymphoid tissue via high endothelial venules. To assess this possibility,
      three patient cohorts were immunized with Ag-pulsed DC by i.v., intradermal
      (i.d.), or intralymphatic (i.l.) injection. All patients developed Ag-specific T
      cell immune responses following immunization, regardless of route. Induction of
      IFN-gamma production, however, was seen only with i.d. and i.l. routes of
      administration, and no IL-4 responses were seen regardless of route, consistent
      with the induction of Th1-type immunity. Five of nine patients who were immunized
      by the i.v. route developed Ag-specific Abs compared with one of six for i.d. and
      two of six for i.l. routes. These results suggest that while activated DC can
      prime T cell immunity regardless of route, the quality of this response and
      induction of Ag-specific Abs may be affected by the route of administration.

PMID- 11238680
TI  - Clinical studies on submicroscopic subtelomeric rearrangements: a checklist.
AB  - BACKGROUND: Submicroscopic subtelomeric chromosome defects have been found in
      7.4% of children with moderate to severe mental retardation and in 0.5% of
      children with mild retardation. Effective clinical preselection is essential
      because of the technical complexities and cost of screening for subtelomere
      deletions. METHODS: We studied 29 patients with a known subtelomeric defect and
      assessed clinical variables concerning birth history, facial dysmorphism,
      congenital malformations, and family history. Controls were 110 children with
      mental retardation of unknown aetiology with normal G banded karyotype and no
      detectable submicroscopic subtelomeric abnormalities. RESULTS: Prenatal onset of
      growth retardation was found in 37% compared to 9% of the controls (p<0.0005). A
      higher percentage of positive family history for mental retardation was reported
      in the study group than the controls (50% v 21%, p=0.002). Miscarriage(s) were
      observed in only 8% of the mothers of subtelomeric cases compared to 30% of
      controls (p=0.028) which was, however, not significant after a Bonferroni
      correction. Common features (>30%) among subtelomeric deletion cases were
      microcephaly, short stature, hypertelorism, nasal and ear anomalies, hand
      anomalies, and cryptorchidism. Two or more facial dysmorphic features were
      observed in 83% of the subtelomere patients. None of these features was
      significantly different from the controls. Using the results, a five item
      checklist was developed which allowed exclusion from further testing in 20% of
      the mentally retarded children (95% CI 13-28%) in our study without missing any
      subtelomere cases. As our control group was selected for the "chromosomal
      phenotype", the specificity of the checklist is likely to be higher in an
      unselected group of mentally retarded subjects. CONCLUSIONS: Our results suggest
      that good indicators for subtelomeric defects are prenatal onset of growth
      retardation and a positive family history for mental retardation. These clinical
      criteria, in addition to features suggestive of a chromosomal phenotype, resulted
      in the development of a five item checklist which will improve the diagnostic
      pick up rate of subtelomeric defects among mentally retarded subjects.

PMID- 11238681
TI  - Clinical and molecular characterisation of 80 patients with 5p deletion: genotype
      phenotype correlation.
AB  - The majority of deletions of the short arm of chromosome 5 are associated with
      cri du chat syndrome (CdCS) and patients show phenotypic and cytogenetic
      variability. To perform a genotype-phenotype correlation, 80 patients from the
      Italian CdCS Register were analysed. Molecular cytogenetic analysis showed that
      62 patients (77.50%) had a 5p terminal deletion characterised by breakpoint
      intervals ranging from p13 (D5S763) to p15.2 (D5S18). Seven patients (8.75%) had
      a 5p interstitial deletion, four (5%) a de novo translocation, and three (3.75%)
      a familial translocation. Of the remaining four patients, three (3.75%) had de
      novo 5p anomalies involving two rearranged cell lines and one (1.25%) had a 5p
      deletion originating from a paternal inversion. The origin of the deleted
      chromosome 5 was paternal in 55 out of 61 patients (90.2%). Genotype-phenotype
      correlation in 62 patients with terminal deletions highlighted a progressive
      severity of clinical manifestation and psychomotor retardation related to the
      size of the deletion. The analysis of seven patients with interstitial deletions
      and one with a small terminal deletion confirmed the existence of two critical
      regions, one for dysmorphism and mental retardation in p15.2 and the other for
      the cat cry in p15.3. Results from one patient permitted the cat cry region to be
      distally narrowed from D5S13 to D5S731. Furthermore, this study lends support to
      the hypothesis of a separate region in p15.3 for the speech delay.

PMID- 11238683
TI  - Association of a novel constitutional translocation t(1q;3q) with familial renal
      cell carcinoma.
AB  - Four cases of late onset clear cell renal cell carcinoma (RCC), a case of gastric
      cancer, and a case of exocrine pancreatic cancer were identified in a Japanese
      family. In order to elucidate the underlying mechanism for tumorigenesis in this
      family, extensive genetic studies were performed including routine and spectral
      karyotyping (SKY), fluorescence in situ hybridisation (FISH), comparative genomic
      hybridisation (CGH), loss of heterozygosity studies (LOH), and VHL mutation
      analysis. A germline translocation t(1;3)(q32-q41;q13-q21) was identified by
      karyotyping in five members of the family including all three RCC cases tested.
      The translocation was refined to t(1;3)(q32;q13.3) by FISH analysis using locus
      specific genomic clones, and the two breakpoints were mapped to a 5 cM region in
      3q13.3 and a 3.6 cM region in 1q32. Both CGH and allelotyping using
      microsatellite markers showed loss of the derivative chromosome 3 carrying a 1q
      segment in the three familial RCCs analysed. Additional chromosomal imbalances
      were identified by CGH, including amplifications of chromosomes 5 and 7 and loss
      of 8p and 9. No germline VHL mutation was found but two different somatic
      mutations, a splice (IVS1-2A>C) and a frameshift (726delG), were identified in
      two RCCs from the same patient confirming their distinct origin. Taken together,
      these results firmly support a three step model for tumorigenesis in this family.
      A constitutional translocation t(1q;3q) increased the susceptibility to loss of
      the derivative chromosome 3 which is then followed by somatic mutations of the
      RCC related tumour suppressor gene VHL located in the remaining copy of
      chromosome 3.

PMID- 11238682
TI  - Male breast cancer in Cowden syndrome patients with germline PTEN mutations.
AB  - Cowden syndrome (CS) (OMIM 158350) is a multiple hamartoma syndrome associated
      with germline mutations in the PTEN tumour suppressor gene. While CS is
      characterised most commonly by non-cancerous lesions (mucocutaneous
      trichilemmomas, acral and palmoplantar keratoses, and papillomatous papules), it
      is also associated with an increased susceptibility to breast cancer (in females)
      and thyroid cancer, as well as non-cancerous conditions of the breast and
      thyroid. Here we report two cases of male breast cancer occurring in patients
      with classical CS phenotypes and germline PTEN mutations. The first subject was
      diagnosed with CS indicated primarily by mucocutaneous papillomatosis, facial
      trichilemmomas, and macrocephaly with frontal bossing at the age of 31 years. He
      developed breast cancer at 41 years and subsequently died of the disease. A PTEN
      mutation, c.802delG, was identified in this subject, yet none of his family
      members showed evidence of a CS phenotype, suggesting that this PTEN mutation may
      be a de novo occurrence. The second subject had a CS phenotype including multiple
      trichilemmomas and thyroid adenoma, developed male breast cancer at 43 years, and
      died of the disease at 57 years. He was a carrier of a PTEN mutation c.347
      351delACAAT that cosegregated with the CS phenotype in affected family members.
      These two cases of male breast cancer associated with germline PTEN mutations and
      the CS phenotype suggest that CS may be associated with an increased risk of
      early onset male as well as female breast cancer.

PMID- 11238685
TI  - A new case of exomphalos, short limbs, and macrogonadism syndrome.

PMID- 11238684
TI  - MECP2 mutation in non-fatal, non-progressive encephalopathy in a male.
AB  - To study the clinical overlap between Rett (RTT) and Angelman syndromes (AS), we
      screened the MECP2 gene in a cohort of 78 patients diagnosed as possible AS but
      who showed a normal methylation pattern at the UBE3A locus. MECP2 missense
      (R106W, G428S), nonsense (R255X, R270X), and frameshift mutations (803 delG) were
      identified in 6/78 patients including 4/6 female cases consistent with RTT, one
      female case with progressive encephalopathy of neonatal onset, and one isolated
      male case with non-fatal, non-progressive encephalopathy of neonatal onset. This
      study shows that MECP2 mutations can account for a broad spectrum of clinical
      presentations and raises the difficult issue of the screening of the MECP2 gene
      in severe encephalopathy in both males and females.

PMID- 11238686
TI  - A partial deletion of the aspartoacylase gene is the cause of Canavan disease in
      a family from Mexico.

PMID- 11238687
TI  - Homoplasmic 3316G-->A in the ND1 gene of the mitochondrial genome: a pathogenic
      mutation or a neutral polymorphism?

PMID- 11238688
TI  - Validating and improving models for projecting the absolute risk of breast
      cancer.

PMID- 11238690
TI  - Despite efficacy of prophylactic mastectomy, procedure finds few enthusiasts.

PMID- 11238689
TI  - Sorting out mutations in human T-cell leukemia virus type 1 proviruses during in
      vivo clonal expansion.

PMID- 11238691
TI  - French National Ad Hoc Committee strongly resists prophylactic mastectomy.

PMID- 11238693
TI  - Stat bite: Average years of life lost from cancer.

PMID- 11238692
TI  - Preventive oncology recognizes 25 years of discoveries.

PMID- 11238694
TI  - African-Americans and prostate cancer: why the discrepancies?

PMID- 11238695
TI  - New gene finding may yield clues to prostate cancer complexity.

PMID- 11238696
TI  - Targeting ceramide metabolism--a strategy for overcoming drug resistance.
AB  - Inherent or acquired drug resistance, which frequently characterizes cancer
      cells, is caused by multiple mechanisms, including dysfunctional metabolism of
      the lipid second messenger ceramide. Ceramide, the basic structural unit of the
      sphingolipids, plays a role in activating cell death signals initiated by
      cytokines, chemotherapeutic agents, and ionizing radiation. Recent discoveries
      about the metabolism of ceramide suggest that this agent may have an important
      influence on the effectiveness of various cancer therapeutics. In particular, the
      cytotoxic effect of chemotherapy is decreased when generation of ceramide is
      impaired but is increased when the degradation of ceramide is blocked. Herein, we
      review the mechanisms of resistance to chemotherapeutic agents in terms of
      ceramide metabolism.

PMID- 11238697
TI  - Validation of the Gail et al. model of breast cancer risk prediction and
      implications for chemoprevention.
AB  - BACKGROUND: Women and their clinicians are increasingly encouraged to use risk
      estimates derived from statistical models, primarily that of Gail et al., to aid
      decision making regarding potential prevention options for breast cancer,
      including chemoprevention with tamoxifen. METHODS: We evaluated both the goodness
      of fit of the Gail et al. model 2 that predicts the risk of developing invasive
      breast cancer specifically and its discriminatory accuracy at the individual
      level in the Nurses' Health Study. We began with a cohort of 82 109 white women
      aged 45-71 years in 1992 and applied the model of Gail et al. to these women over
      a 5-year follow-up period to estimate a 5-year risk of invasive breast cancer.
      All statistical tests were two-sided. RESULTS: The model fit well in the total
      sample (ratio of expected [E] to observed [O] numbers of cases = 0.94; 95%
      confidence interval [CI] = 0.89 to 0.99). Underprediction was slightly greater
      for younger women (<60 years), but in most age and risk factor strata, E/O ratios
      were close to 1.0. The model fit equally well (E/O ratio = 0.93; 95% CI = 0.87 to
      0.99) in a subset of women reporting recent screening (i.e., within 1 year before
      the baseline); among women with an estimated 5-year risk of developing invasive
      breast cancer of 1.67% or greater, the E/O ratio was 1.04 (95% CI = 0.96 to
      1.12). The concordance statistic, which indicates discriminatory accuracy, for
      the Gail et al. model 2 when used to estimate 5-year risk was 0.58 (95% CI = 0.56
      to 0.60). Only 3.3% of the 1354 cases of breast cancer observed in the cohort
      arose among women who fell into age-risk strata expected to have statistically
      significant net health benefits from prophylactic tamoxifen use. CONCLUSIONS: The
      Gail et al. model 2 fit well in this sample in terms of predicting numbers of
      breast cancer cases in specific risk factor strata but had modest discriminatory
      accuracy at the individual level. This finding has implications for use of the
      model in clinical counseling of individual women.

PMID- 11238699
TI  - Metabolites of a tobacco-specific lung carcinogen in nonsmoking women exposed to
      environmental tobacco smoke.
AB  - BACKGROUND: Environmental tobacco smoke (ETS) is associated with lung cancer in
      nonsmokers. Most epidemiologic studies find a higher risk for lung cancer in
      nonsmoking women married to smokers than in those married to nonsmokers. We
      measured metabolites of a tobacco-specific lung carcinogen in urine from healthy,
      nonsmoking women exposed to ETS. METHODS: We recruited women and their partners
      through advertisements. Couples completed questionnaires on smoking history and
      demographics, and both partners provided 100 mL of urine; 23 women had male
      partners who smoked in the home (i.e., exposed women), and 22 women had male
      partners who did not smoke (i.e., unexposed women). Urine samples were analyzed
      for nicotine, for cotinine, for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol
      (NNAL) and its glucuronide (NNAL-Gluc), as well as for creatinine. NNAL and NNAL
      Gluc are metabolites of the tobacco-specific lung carcinogen 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Unpaired Student's t tests
      were conducted on log-transformed values. All statistical tests are two-sided.
      RESULTS: Urinary levels of nicotine, cotinine, NNAL, and NNAL-Gluc were
      statistically significantly higher in exposed women than in unexposed women.
      Geometric means for these compounds in exposed versus unexposed women,
      respectively, were as follows: nicotine, 0.050 nmol/mg of creatinine (95%
      confidence interval [CI] = 0.033 to 0.076) versus 0.008 nmol/mg of creatinine
      (95% CI = 0.004 to 0.014); cotinine, 0.037 nmol/mg of creatinine (95% CI = 0.022
      to 0.061) versus 0.007 nmol/mg of creatinine (95% CI = 0.004 to 0.011); NNAL,
      0.013 pmol/mg of creatinine (95% CI = 0.007 to 0.024) versus 0.004 pmol/mg of
      creatinine (95% CI = 0.002 to 0.007); and NNAL-Gluc, 0.027 pmol/mg of creatinine
      (95% CI = 0.016 to 0.045) versus 0.004 pmol/mg of creatinine (95% CI = 0.003 to
      0.006). CONCLUSIONS: Nonsmoking women exposed to ETS take up and metabolize the
      tobacco-specific lung carcinogen NNK, which could increase their risk of lung
      cancer. Within couples, the NNAL plus NNAL-Gluc level in exposed women compared
      with that of their smoking partners averaged 5.6%. Notably, epidemiologic studies
      have estimated the excess risk for lung cancer in nonsmoking women exposed to ETS
      as 1%-2% of that in smokers.

PMID- 11238698
TI  - Somatic mutation in human T-cell leukemia virus type 1 provirus and flanking
      cellular sequences during clonal expansion in vivo.
AB  - BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1), the causative agent of
      adult T-cell leukemia/lymphoma, shows intrapatient genetic variability. Although
      HTLV-1 can replicate via the reverse transcription of virion RNA to a double
      stranded DNA provirus (the conventional manner for retroviruses), its predominant
      mode of replication is via the clonal expansion (mitosis) of the infected cell.
      This expansion is achieved by the viral oncoprotein Tax, which keeps the infected
      CD4 T lymphocyte cycling. Because Tax also interferes with cellular DNA repair
      pathways, we investigated whether somatic mutations of the provirus that occur
      during the division of infected cells could account for HTLV-1 genetic
      variability. METHODS: An inverse polymerase chain reaction strategy was designed
      to distinguish somatic mutations from reverse transcription-associated
      substitutions. This strategy allows the proviral sequences to be isolated
      together with flanking cellular sequences. Using this method, we sequenced 208
      HTLV-1 provirus 3' segments, together with their integration sites, belonging to
      29 distinct circulating cellular clones from infected individuals. RESULTS: For
      60% of the clones, 8%-80% of infected cells harbored a mutated HTLV-1 provirus,
      without evidence of reverse transcription-associated mutations. Mutations within
      flanking cellular sequences were also identified at a frequency of 2.8 x 10(-4)
      substitution per base pair. Some of these clones carried multiple discrete
      substitutions or deletions, indicating progressive accumulation of mutations
      during clonal expansion. The overall frequency of somatic mutations increased
      with the degree of proliferation of infected T cells. CONCLUSIONS: These data
      indicate that, in vivo, HTLV-1 variation results mainly from postintegration
      events that consist of somatic mutations of the proviral sequence occurring
      during clonal expansion. The finding of substitutions in flanking sequences
      suggests that somatic mutations occurring after integration, presumably coupled
      with selection, help move the cellular clones toward a transformed phenotype, of
      which adult T-cell leukemia/lymphoma is the end point.

PMID- 11238700
TI  - Effect of antiangiogenic therapy on slowly growing, poorly vascularized tumors in
      mice.
AB  - BACKGROUND: Angiogenesis is essential for tumor growth and progression.
      Therefore, inhibition of angiogenesis is being studied as a new anticancer
      therapy. Because cytotoxic chemotherapy is more effective on rapidly growing
      tumors than on slowly growing tumors, it has been assumed that antiangiogenic
      therapy will also be effective only on rapidly growing, highly vascularized
      tumors. We compared the effects of two angiogenesis inhibitors, TNP-470 and
      angiostatin, on slowly growing, poorly vascularized and rapidly growing, highly
      vascularized human tumors in mice. METHODS: Slowly growing (RT-4) and rapidly
      growing (MGH-U1) human bladder carcinoma cell lines were grown in severe combined
      immunodeficiency mice. Established tumors were treated with one of the two
      angiogenesis inhibitors. Tumor volumes, vascularity, and proliferation indices
      were determined. The in vitro effects of TNP-470 and of angiostatin on the
      proliferation of RT-4 and MGH-U1 cells were also investigated. All statistical
      tests were two-sided. RESULTS: RT-4 and MGH-U1 tumor growth was statistically
      significantly inhibited by both angiogenesis inhibitors (P<.001). Both inhibitors
      decreased the blood vessel density in both tumor types but did not alter the in
      vivo proliferation indices of the tumors. TNP-470, but not angiostatin,
      marginally decreased the in vitro proliferation of MGH-U1 cells. CONCLUSION:
      Slowly growing, poorly vascularized tumors in animal models respond as well as
      rapidly growing, highly vascularized tumors to therapy with the angiogenesis
      inhibitors TNP-470 and angiostatin.

PMID- 11238701
TI  - Racial and ethnic differences in advanced-stage prostate cancer: the Prostate
      Cancer Outcomes Study.
AB  - BACKGROUND: African-Americans have twice the risk of non-Hispanic whites for
      presenting with advanced-stage prostate cancer. To investigate the reasons for
      this difference, we evaluated the association between race/ethnicity and advanced
      stage prostate cancer, adjusting for demographic, socioeconomic, clinical, and
      pathologic factors. METHODS: A population-based cohort of 3173 men diagnosed with
      prostate cancer between October 1, 1994, and October 31, 1995, was analyzed.
      Medical record abstracts and self-administered survey questionnaires were used to
      obtain information regarding race/ethnicity, age, marital status, insurance
      status, educational level, household income, employment status, comorbidity,
      urinary function, prostate-specific antigen level, tumor grade, and clinical
      stage. The odds ratio (OR) for advanced-stage prostate cancer was estimated with
      weighted logistic regression analysis. All P: values were two-sided. RESULTS:
      Clinically advanced-stage prostate cancers were detected more frequently in
      African-Americans (12.3%) and Hispanics (10.5%) than in non-Hispanic whites
      (6.3%). Socioeconomic, clinical, and pathologic factors each accounted for about
      15% of the increased relative risk. After adjusting for all covariates, the risk
      remained statistically significantly increased for African-Americans (OR = 2.26;
      95% confidence interval [CI] = 1.43 to 3.58) but not for Hispanics (OR = 1.23;
      95% CI = 0.73 to 2.08). CONCLUSION: Traditional socioeconomic, clinical, and
      pathologic factors accounted for the increased relative risk for presenting with
      advanced-stage prostate cancer in Hispanic but not in African-American men.

PMID- 11238702
TI  - Re: Canadian national breast screening study-2: 13-year results of a randomized
      trial in women aged 50-59 years.

PMID- 11238705
TI  - Re: Efforts aimed at risk communication flourish.

PMID- 11238704
TI  - Re: Causes of death in elderly prostate cancer patients and in a comparison
      nonprostate cancer cohort.

PMID- 11238707
TI  - Re: A model to select chemotherapy regimens for phase III trials for extensive
      stage small-cell lung cancer.

PMID- 11238710
TI  - Re: Health outcomes after prostatectomy or radiotherapy for prostate cancer:
      results from the Prostate Cancer Outcomes Study.

PMID- 11238711
TI  - The parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): a
      technical review of its utility and safety.

PMID- 11238712
TI  - Molecular cloning and characterization of hNP22: a gene up-regulated in human
      alcoholic brain.
AB  - An improved differential display technique was used to search for changes in gene
      expression in the superior frontal cortex of alcoholics. A cDNA fragment was
      retrieved and cloned. Further sequence of the cDNA was determined from 5' RACE
      and screening of a human brain cDNA library. The gene was named hNP22 (human
      neuronal protein 22). The deduced protein sequence of hNP22 has an estimated
      molecular mass of 22.4 kDa with a putative calcium-binding site, and
      phosphorylation sites for casein kinase II and protein kinase C. The deduced
      amino acid sequence of hNP22 shares homology (from 67% to 42%) with four other
      proteins, SM22alpha, calponin, myophilin and mp20. Sequence homology suggests a
      potential interaction of hNP22 with cytoskeletal elements. hNP22 mRNA was
      expressed in various brain regions but in alcoholics, greater mRNA expression
      occurred in the superior frontal cortex, but not in the primary motor cortex or
      cerebellum. The results suggest that hNP22 may have a role in alcohol-related
      adaptations and may mediate regulatory signal transduction pathways in neurones.

PMID- 11238713
TI  - Modulation of the neuronal dopamine transporter activity by the metabotropic
      glutamate receptor mGluR5 in rat striatal synaptosomes through phosphorylation
      mediated processes.
AB  - There is considerable evidence that the activity of the neuronal dopamine
      transporter (DAT) is dynamically regulated and a putative implication of its
      phosphorylation in this process has been proposed. However, there is little
      information available regarding the nature of physiological stimuli that
      contribute to the endogenous control of the DAT function. Based on the close
      relationship between glutamatergic and dopaminergic systems in the striatum, we
      investigated the modulation of the DAT activity by metabotropic glutamate
      receptors (mGluRs). Short-term incubations of rat striatal synaptosomes with
      micromolar concentrations of the group I mGluR selective agonist (S)-3,5
      dihydroxyphenylglycine were found to significantly decrease the DAT capacity and
      efficiency. This alteration was completely prevented by a highly selective mGluR5
      antagonist, 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP). The effect
      of (S)-3,5-dihydroxyphenylglycine was also inhibited by staurosporine and by
      selective inhibitors of protein kinase C and calcium calmodulin-dependent protein
      kinase II. Co-application of okadaic acid prolonged the transient effect of the
      agonist, supporting a critical role for phosphorylation in the modulation of the
      DAT activity by mGluRs. In conclusion, we propose that striatal mGluR5 contribute
      to the control of the DAT activity through concomitant activation of both protein
      kinase C and calcium calmodulin-dependent protein kinase II.

PMID- 11238714
TI  - Metabolic fate of AMP, IMP, GMP and XMP in the cytosol of rat brain: an
      experimental and theoretical analysis.
AB  - A systematic study of the metabolic fate of AMP, IMP, GMP and XMP (NMP) in the
      presence of cytosol from rat brain is here presented; the kinetics of both
      disappearance of NMP, and appearance of their degradation products was followed
      by HPLC. In the absence of ATP, AMP was preferentially degraded to adenosine with
      concomitant appearance of inosine and hypoxanthine. In the presence of ATP, AMP
      was preferentially degraded via IMP. The nucleosides generated in the course of
      the reactions are further degraded, almost exclusively, via nucleoside
      phosphorylase using as cofactor the P(i) generated in the reaction mixture. In
      order to quantify the effect of each one of the enzymes involved in the
      degradation of NMP, two complementary approaches were followed: (i) the V:(max)
      and K:(m) values of the enzymes acting in the intermediate steps of the reactions
      were determined; (ii) these data were introduced into differential equations
      describing the concentration of the nucleotides and their degradation products as
      a function of the time of incubation. Factors affecting kinetic parameters of the
      equation velocity as a function of ATP concentration were introduced when
      required. The differential equations were solved with the help of Mathematica
      3.0. The theoretical method can be used to simulate situations not feasible to be
      carried out, such as to measure the influence of nM-microM concentrations of ATP
      on the metabolism of AMP.

PMID- 11238715
TI  - A dinucleotide deletion in amyloid precursor protein (APP) mRNA associated with
      sporadic Alzheimer's disease results in efficient secretion of truncated APP
      isoforms from neuroblastoma cell cultures.
AB  - Recently, two dinucleotide deletions were detected in the mRNA of the amyloid
      precursor protein (APP) from cerebral cortex neurons of patients with sporadic
      Alzheimer's disease (AD) or Down's syndrome. These deletions resulted in
      truncation of APP, producing an APP isoform with a 38-kDa N-terminus and a novel
      carboxyl terminus (APP+1). We investigated the subcellular localization and the
      processing of APP+1 in the neuroblastoma cell line B103. cDNA constructs were
      generated encoding fusion proteins of APP+1 or full-length APP with the enhanced
      green fluorescent protein (eGFP). In transient transfection experiments using
      B103 cells, the APP+1-eGFP fusion protein showed a reticular localization with
      intense staining in the Golgi complex. Unlike full-length APP fused to eGFP, the
      APP+1-eGFP fusion protein did not localize to the perinuclear area or to the
      plasma membrane. Western blot analysis of cell extracts confirmed the translation
      of the expected fusion proteins. Analysis of the supernatant by western blot
      indicated that the APP+1-eGFP fusion protein was efficiently secreted from B103
      cells, whereas the secreted form of full-length APP fusion protein (APPs) was
      hardly detectable. Thus, both dinucleotide deletions in the APP mRNA result in
      truncated APP+1 that is not membrane associated and is readily secreted from
      neurons.

PMID- 11238716
TI  - Phosphorylation state of the native high-molecular-weight neurofilament subunit
      protein from cervical spinal cord in sporadic amyotrophic lateral sclerosis.
AB  - The intraneuronal aggregation of phosphorylated high-molecular-weight
      neurofilament protein (NFH) in spinal cord motor neurons is considered to be a
      key pathological marker of amyotrophic lateral sclerosis (ALS). In order to
      determine whether this observation is due to the aberrant or hyper
      phosphorylation of NFH, we have purified and characterized NFH from the cervical
      spinal cords of ALS patients and controls. We observed no differences between ALS
      and normal controls in the physicochemical properties of NFH in Triton X-100
      insoluble protein fractions, with respect to migration patterns on 2D-iso
      electrofocusing (IEF) gels, the rate of Escherichia coli alkaline phosphatase
      mediated dephosphorylation, or the rate of calpain-mediated proteolysis. The rate
      of calpain-mediated proteolysis was unaffected by either exhaustive NFH
      dephosphorylation or by the addition of calmodulin to the reaction.
      Phosphopeptides and the phosphorylated motifs characterized by liquid
      chromatography tandem mass spectroscopy (LC/MS/MS) analysis demonstrated that all
      the phosphorylated residues found in ALS NFH were also found to be phosphorylated
      in normal human NFH samples. Hence, we have observed no difference in the
      physicochemical properties of normal and ALS NFH extracted from cervical spinal
      cords, suggesting that the perikaryal aggregation of highly phosphorylated NF in
      ALS neurons reflects the aberrant somatotopic localization of normally
      phosphorylated NFH.

PMID- 11238717
TI  - Central beta-amyloid peptide-induced peripheral interleukin-6 responses in mice.
AB  - beta-Amyloid peptides (Abetas) share with lipopolysaccharide, a potent pro
      inflammatory agent, the property of stimulating glial cells or macrophages to
      induce various inflammatory mediators. We recently reported that central
      administration of lipopolysaccharide induces peripheral interleukin-6 responses
      via both the central and peripheral norepinephrine system. In this study, the
      effect of intracerebroventricular injection of various synthetic Abetas on plasma
      interleukin-6 levels was examined in mice. Abeta(1-42) dose-dependently increased
      plasma interleukin-6 levels: 'aged' Abeta(1-42) was more effective than fresh,
      whereas Abeta(42-1) had no effect. 'Aged' Abeta(1-42) (205 pmol/mouse i.c.v.)
      induced plasma interleukin-6 peaked at 2 h post injection, which is earlier than
      the peak time of the Abeta(1-42)-induced brain interleukin-6, tumor necrosis
      factor-alpha and interleukin-1beta levels, which was 4, 4 and 24 h, respectively.
      Among various peripheral organs, Abeta(1-42) (205 pmol/mouse i.c.v.)
      significantly increased interleukin-6 mRNA expression in lymph nodes and liver.
      Abeta(1-42) (205 pmol/mouse i.c.v.) significantly increased norepinephrine
      turnover in both hypothalamus and spleen. Either central or peripheral
      norepinephrine depletion effectively inhibited the Abeta(1-42)-induced peripheral
      interleukin-6 response. Pretreatment with prazosin (alpha(1)-adrenergic
      antagonist), yohimbine (alpha(2)-adrenergic antagonist), and ICI-118,551 (beta(2)
      adrenergic antagonist), but not with betaxolol (beta(1)-adrenergic antagonist),
      inhibited Abeta(1-42)-induced plasma interleukin-6 levels. These results
      demonstrate that centrally administered Abeta(1-42) effectively induces the
      systemic interleukin-6 response which is mediated, in part, by central Abeta(1
      42)-induced activation of the central and the peripheral norepinephrine systems.

PMID- 11238718
TI  - Superoxide dismutase activity in organotypic midbrain-striatum co-cultures is
      associated with resistance of dopaminergic neurons to excitotoxicity.
AB  - We have previously demonstrated that dopaminergic neurons in midbrain-striatum
      slice co-cultures are more resistant to NMDA cytotoxicity than the same neuronal
      population in single midbrain slice cultures. Here, we show that dopaminergic
      neurons in midbrain-striatum co-cultures also exhibit resistance to the
      cytotoxicity of nitric oxide donors, 2,2'-(hydroxynitrosohydrazono)bis-ethanamine
      (NOC-18) and 3-morpholinosydnonimine (SIN-1). The cytotoxicity of NMDA (30
      microM) in single cultures was significantly attenuated by the nitric oxide
      synthase (NOS) inhibitor N(omega)-nitro-L-arginine (100 microM), whereas the
      toxicity in co-cultures was not. The levels of tyrosine residue nitration of
      tyrosine hydroxylase, a hallmark of the occurence of peroxynitrite anion in
      dopaminergic neurons, were lower in co-cultures than those in single cultures.
      Single cultures and co-cultures did not show appreciable differences in the
      number or distribution of NOS-containing neurons as assessed by NADPH diaphorase
      histochemistry. On the other hand, midbrain slices cultured with striatal slices
      showed higher levels of superoxide dismutase (SOD) activity as well as increased
      protein levels of Cu,Zn-SOD, than midbrain slices cultured alone. These results
      suggested that the generation of NO is involved in NMDA cytotoxicity on
      dopaminergic neurons, and that increased activity of SOD in co-cultures renders
      dopaminergic neurons resistant to NMDA cytotoxicity by preventing the formation
      of peroxynitrite.

PMID- 11238719
TI  - Activation of 5-HT(1A) but not 5-HT(1B) receptors attenuates an increase in
      extracellular dopamine derived from exogenously administered L-DOPA in the
      striatum with nigrostriatal denervation.
AB  - In order to determine whether L-DOPA-derived extracellular dopamine (DA) in the
      striatum with dopaminergic denervation is affected by activation of serotonin
      autoreceptors (5-HT(1A) and 5-HT(1B) receptors), we applied in vivo brain
      microdialysis technique to 6-hydroxydopamine-lesioned rats and examined the
      effects of the selective 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n
      propylamino)tetralin (8-OH-DPAT) and the selective 5-HT(1B) receptor agonist CGS
      12066 A on L-DOPA-derived extracellular DA levels. Single L-DOPA injection (50
      mg/kg i.p.) caused a rapid increase and a following decrease of extracellular DA,
      with a peak value at 100 min after L-DOPA injection. Pretreatment with both 0.3
      mg/kg and 1 mg/kg 8-OH-DPAT (i.p.) significantly attenuated an increase in L-DOPA
      derived extracellular DA and the times of peak DA levels were prolonged to 150
      min and 225 min after L-DOPA injection, respectively. These 8-OH-DPAT-induced
      changes in L-DOPA-derived extracellular DA were antagonized by further
      pretreatment with WAY-100635, a selective 5-HT(1A) antagonist. In contrast,
      intrastriatal perfusion with the 5-HT(1B) agonist CGS-12066 A (10 nM and 100 nM)
      did not induce any changes in L-DOPA-derived extracellular DA. Thus, stimulation
      of 5-HT(1A) but not 5-HT(1B) receptors attenuated an increase in extracellular DA
      derived from exogenous L-DOPA. These results support the hypothesis that
      serotonergic neurons are primarily responsible for the storage and release of DA
      derived from exogenous L-DOPA in the absence of dopaminergic neurons.

PMID- 11238720
TI  - Differential effects of ethanol on the expression of cyclo-oxygenase in cultured
      cortical astrocytes and neurons.
AB  - The developing central nervous system is a primary target of ethanol toxicity.
      The teratogenic effect of ethanol may result from its action on prostaglandins.
      Prostaglandins are generated through the release of arachidonic acid (AA) by the
      action of cytosolic phospholipase A(2) (cPLA(2)) on membrane-bound phospholipids
      and the catalytic conversion of AA to prostaglandin E(2) (PGE(2)) by cyclo
      oxygenase (COX). COX is expressed in two isoforms, constitutive COX1 and
      inducible COX2. Cultured astrocytes and neurons from immature cerebral cortex
      were used as in vitro models to investigate the effect of ethanol on PGE(2)
      synthesis. In both cell types, neither the activity nor the expression of cPLA(2)
      was affected by ethanol. PGE(2) was synthesized by astrocytes and neurons.
      Ethanol (200-400 mg/dL for 24 h) significantly increased PGE(2) production in
      both cell types and the ethanol-induced increase in PGE(2) accumulation in
      astrocytes was significantly greater than in neurons. These increases resulted
      from the effects of ethanol on COX. Overall COX activity was up-regulated by
      ethanol in astrocytes and neurons, and indomethacin, a nonselective blocker for
      COX, eliminated the ethanol-induced increases of COX activity in both cell types.
      Increased COX activity in astrocytes resulted from an increase in COX2
      expression. NS-398, a selective COX2 blocker, completely inhibited ethanol
      induced alterations in COX activity. In neurons, however, ethanol had a direct
      effect on COX activity in the absence of a change in COX expression. NS-398 only
      partially blocked ethanol-induced increases in neuronal COX activity. Thus,
      astrocytes are a primary target of ethanol and ethanol-induced increases in glial
      PGE(2) synthesis are mediated by COX, principally COX2. Ethanol toxicity may be
      mediated through PGE(2) in immature cortical cells.

PMID- 11238721
TI  - Light scattering and transmission electron microscopy studies reveal a mechanism
      for calcium/calmodulin-dependent protein kinase II self-association.
AB  - Calmodulin (CaM)-kinase II holoenzymes composed of either alpha or beta subunits
      were analyzed using light scattering to determine a mechanism for self
      association. Under identical reaction conditions, only alphaCaM-kinase II
      holoenzymes self-associated. Self-association was detected at a remarkably low
      enzyme concentration (0.14 microM or 7 microg/mL). Light scattering revealed two
      phases of self-association: a rapid rise that peaked, followed by a slower
      decrease that stabilized after 2-3 min. Electron microscopy identified that the
      rapid rise in scattering was due to the formation of loosely packed clusters of
      holoenzymes that undergo further association into large complexes of several
      microns in diameter over time. Self-association required activation by Ca(2+)/CaM
      and was strongly dependent on pH. Self-association was not detected at pH 7.5,
      however, the extent of this process increased as reaction pH decreased below 7.0.
      A peptide substrate (autocamtide-2) and inhibitor (AIP) designed from the
      autoregulatory domain of CaM-kinase II potently prevented self-association,
      whereas the peptide substrate syntide-2 did not. Thus, CaM-kinase II self
      association is isoform specific, regulated by the conditions of activation, and
      is inhibited by peptides that bind to the catalytic domain likely via their
      autoregulatory-like sequence. A model for CaM-kinase II self-association is
      presented whereby catalytic domains in one holoenzyme interact with the
      regulatory domains in neighboring holoenzymes. These intersubunit-interholoenzyme
      autoinhibitory interactions could contribute to both the translocation and
      inactivation of CaM-kinase II previously reported in models of ischemia.

PMID- 11238722
TI  - The cAMP responsive element and CREB partially mediate the response of the
      tyrosine hydroxylase gene to phorbol ester.
AB  - Tyrosine hydroxylase (TH) gene promoter activity is increased in PC12 cells that
      are treated with the phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA).
      Mutagenesis of either the cAMP responsive element (CRE) or the activator protein
      1 element (AP1) within the TH gene proximal promoter leads to a dramatic
      inhibition of the TPA response. The TH CRE and TH AP1 sites are also
      independently responsive to TPA in minimal promoter constructs. TPA treatment
      results in phosphorylation of cAMP responsive element binding protein (CREB) and
      activation of cAMP-dependent protein kinase (PKA) in PC12 cells; hence, we tested
      whether CREB and/or PKA are essential for the TPA response. In CREB-deficient
      cells, the response of the full TH gene proximal promoter or the independent
      response of the TH CRE by itself to TPA is inhibited. The TPA-inducibility of TH
      mRNA is also blocked in CREB-deficient cells. Expression of the PKA inhibitor
      protein, PKI, also inhibits the independent response of the TH CRE to TPA. Our
      results support the hypothesis that TPA stimulates the TH gene promoter via
      signaling pathways that activate either the TH AP1 or TH CRE sites. Both
      signaling pathways are dependent on CREB and the TH CRE-mediated pathway is
      dependent on PKA.

PMID- 11238723
TI  - Reduction of functional N-methyl-D-aspartate receptors in neurons by RNase P
      mediated cleavage of the NR1 mRNA.
AB  - One approach to studying the functional role of individual NMDA receptor subunits
      involves the reduction in the abundance of the protein subunit in neurons. We
      have pursued a strategy to achieve this goal that involves the use of a small
      guide RNA which can lead to the destruction of the mRNA for a specific receptor
      subunit. We designed a small RNA molecule, termed 'external guide sequence'
      (EGS), which binds to the NR1 mRNA and directs the endonuclease RNase P to cleave
      the target message. This EGS has exquisite specificity and directed the RNase P
      dependent cleavage at the targeted location within the NR1 mRNA. To improve the
      efficiency of this EGS, an in vitro evolution strategy was employed which led to
      a second generation EGS that was 10 times more potent than the parent molecule.
      We constructed an expression cassette by flanking the EGS with self-cleaving
      ribozymes and this permitted generation of the specified EGS RNA sequence from
      any promoter. Using a recombinant Herpes simplex virus (HSV), we expressed the
      EGS in neurons and showed the potency of the EGS to reduce NR1 protein within
      neurons. In an excitotoxicity assay, we showed that expression of the EGS in
      cortical neurons is neuroprotective. Our results demonstrate the utility of EGSs
      to reduce the expression of any gene (and potentially any splice variant) in
      neurons.

PMID- 11238724
TI  - Nicotine protects against arachidonic-acid-induced caspase activation, cytochrome
      c release and apoptosis of cultured spinal cord neurons.
AB  - Hydrolysis of membrane phospholipids of spinal cord neurons is one of the first
      events initiated in spinal cord trauma. In this process, free fatty acids, and in
      particular arachidonic acid, are released. Exposure of spinal cord neurons to
      free arachidonic acid can compromise cell survival and initiate apoptotic cell
      death. In order to determine potential mechanisms of apoptosis induced by
      arachidonic acid, activation of caspases -3, -8, and -9, as well as the release
      of cytochrome c into the cytoplasm were measured in cultured spinal cord neurons
      exposed to 10 microM of this fatty acid. In addition, because nicotine can exert
      a variety of neuroprotective effects, we hypothesized that it can prevent
      arachidonic acid induced apoptosis of spinal cord neurons. To study this
      hypothesis, spinal cord neurons were pretreated with nicotine (10 microM for 2 h)
      before arachidonic acid exposure and caspase activation as well as markers of
      apoptotic cell death were studied. Treatment of spinal cord neurons with
      arachidonic acid for up to 24 h significantly increased cytoplasmic levels of
      cytochrome c, induced caspase activation and induced DNA laddering, a hallmark of
      apoptotic cell death. Nicotine pretreatment markedly attenuated all these
      effects. In addition, antagonist studies suggest that the alpha7 nicotinic
      receptor is primarily responsible for these anti-apoptotic effects of nicotine.
      These results indicate that nicotine can exert potent neuroprotective effects by
      inhibiting arachidonic acid induced apoptotic cascades of spinal cord neurons.

PMID- 11238725
TI  - Visualization of oxygen-concentration-dependent production of nitric oxide in rat
      hippocampal slices during aglycemia.
AB  - Our novel fluorescent indicator, DAF-FM, permits the bioimaging of nitric oxide
      (NO) in living cells with high resolution in space and time, with stable
      intensity above pH 5.8. A membrane-permeable derivative, DAF-FM DA, was applied
      to imaging of NO generated in rat hippocampal slices by exposure to an aglycemic
      medium. NO production was observed mainly in the CA1 area, and was dependent on
      the concentration of O(2). During exposure to an anoxic-aglycemic medium, NO was
      hardly produced, while marked elevation of intracellular Ca(2+) was observed.
      Production of NO increased sharply as soon as the perfusate was changed to the
      normal medium. These results suggest that NO synthase is activated after
      reperfusion rather than during ischemia.

PMID- 11238726
TI  - Fibulin-1 binds the amino-terminal head of beta-amyloid precursor protein and
      modulates its physiological function.
AB  - Genetic studies have implicated amyloid precursor protein (APP) in the
      pathogenesis of Alzheimer's disease. While accumulating lines of evidence
      indicate that APP has various functions in cells, little is known about the
      proteins that modulate its biological activity. Toward this end, we employed a
      two-hybrid system to identify potential interacting factors. We now report that
      fibulin-1, which contains repetitive Ca(2+)-binding EGF-like elements, binds to
      APP at its amino-terminal growth factor-like domain, the region that is
      responsible for its neurotrophic activities. Fibulin-1 expression in the brain is
      confined to neurons, and is not expressed significantly by astrocytes or
      microglia. Direct binding of fibulin-1 to the secreted form of APP (sAPP) was
      demonstrated with a pull-down assay using fragments of both fibulin-1 fused with
      glutathione-S transferase and sAPP, produced in bacteria and yeast, respectively.
      The fibulin-1/sAPP heteromer was shown to form in the conditioned medium of
      transfected COS-7 cells. Furthermore, fibulin-1 blocks sAPP-mediated
      proliferation of primary cultured rat neural stem cells. These results suggest
      that fibulin-1 may play a significant role in modulating the neurotrophic
      activities of APP.

PMID- 11238727
TI  - Soluble N-cadherin stimulates fibroblast growth factor receptor dependent neurite
      outgrowth and N-cadherin and the fibroblast growth factor receptor co-cluster in
      cells.
AB  - A chimeric molecule consisting of the extracellular domain of the adhesion
      molecule, N-cadherin, fused to the Fc region of human IgG (NCAD-Fc) supports
      calcium-dependent cell adhesion and promotes neurite outgrowth following affinity
      capture to a tissue culture substrate. When presented to cerebellar neurons as a
      soluble molecule, the NCAD-Fc stimulated neurite outgrowth in a manner equivalent
      to that seen for N-cadherin expressed as a cell surface glycoprotein. Neurons
      expressing a dominant-negative version of the fibroblast growth factor (FGF)
      receptor did not respond to soluble NCAD-Fc. In cells transfected with full
      length N-cadherin and the FGF receptor, antibody-clustering of N-cadherin
      resulted in a co-clustering of the FGF receptor to discrete patches in the cell
      membrane. The data demonstrate that the ability of N-cadherin to stimulate
      neurite outgrowth can be dissociated from its ability to function as a substrate
      associated adhesion molecule. The N-cadherin and the FGF receptor co-clustering
      in cells provides a basis for the neurite outgrowth response stimulated by N
      cadherin being dependent on FGF receptor function.

PMID- 11238728
TI  - Inhibition of tumour necrosis factor-alpha (TNFalpha)-induced NF-kappaB p52
      converts the metabolic effects of microglial-derived TNFalpha on mouse cerebellar
      neurones to neurotoxicity.
AB  - Activated microglia are implicated in the injury of neurones and macroglia both
      in vitro and in vivo. Here, we demonstrate that media conditioned by interferon
      gamma treated microglia initially impair the metabolism of mouse cerebellar
      neurones grown in serum-free conditions without inducing cell death. Metabolic
      effects include inhibition of the ability of mitochondria to reduce 3-[4,5
      dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and cytochrome
      oxidase activity. These effects are blocked by antibodies to tumour necrosis
      factor-alpha (TNFalpha), a cytokine produced by microglial activation, and they
      are not reproduced by media conditioned by resting microglia. The metabolic
      effects are evident for up to 24 h in vitro. More prolonged exposure, up to 48 h,
      results in TNFalpha dependent neuronal death as previously observed. Between 2
      and 48 h TNFalpha present in media conditioned by interferon-gamma treated but
      not resting microglia is associated with nuclear factor kappa B (NF-kappaB)
      consensus sequence binding in paired mouse cerebellar neuronal cultures without
      affecting activation of the signal transducer and activator of transcription
      (STAT) transcription factor. Neuronal death can be accelerated by peptide
      blockade of the nuclear transport of NF-kappaB p52 subunit during exposure of
      cerebellar neurones to medium from interferon-gamma treated microglia. This
      toxicity is blocked by anti-TNFalpha antibody. Soluble factors released by
      activated microglia therefore contribute to neuronal dysfunction that is
      initially reversible but may culminate in neurotoxicity. Characterizing and
      manipulating these events in vivo theoretically provides an opportunity for
      neuroprotection in selected diseases affecting the central nervous system.

PMID- 11238729
TI  - Direct inhibition of c-Jun N-terminal kinase in sympathetic neurones prevents c
      jun promoter activation and NGF withdrawal-induced death.
AB  - c-Jun N-terminal kinases (JNKs) regulate gene expression by phosphorylating
      transcription factors, such as c-Jun. Studies with JNK: knockout mice suggest
      that JNK activity may be required for excitotoxin-induced apoptosis in the adult
      hippocampus and for apoptosis in the developing embryonic neural tube. Here we
      investigate the role of JNKs in classical neurotrophin-regulated developmental
      neuronal death by using nerve growth factor (NGF)-dependent sympathetic neurones.
      In this system, NGF withdrawal leads to an increase in JNK activity, an increase
      in c-Jun protein levels and c-Jun N-terminal phosphorylation before the cell
      death commitment point, and c-Jun activity is required for cell death. To inhibit
      JNK activity in sympathetic neurones we have used two different JNK inhibitors
      that act by distinct mechanisms: the compound SB 203580 and the JNK binding
      domain (JBD) of JNK interacting protein 1 (JIP-1). We demonstrate that JNK
      activity is required for c-Jun phosphorylation, c-jun promoter activation and NGF
      withdrawal-induced apoptosis. We also show that ATF-2, a c-Jun dimerization
      partner that can regulate c-jun gene expression, is activated following NGF
      deprivation. Finally, by co-expressing the JBD and a regulatable c-Jun dominant
      negative mutant we demonstrate that JNK and AP-1 function in the same pro
      apoptotic signalling pathway after NGF withdrawal.

PMID- 11238731
TI  - Molecular cloning and functional characterization of a novel delayed rectifier
      potassium channel from channel catfish (Ictalurus punctatus): expression in taste
      buds.
AB  - The gustatory system of channel catfish is widely studied for its sensitivity to
      amino acids. As a first step in identifying the molecular components that play a
      role in taste transduction in catfish, we cloned the full-length cDNA for Kv2
      catfish, a novel K(+) channel that is expressed in taste buds. The deduced amino
      acid sequence is 816 residues, and shares a 56-59% sequence identity with Kv2.1
      and Kv2.2, the other members of the vertebrate Kv2 subfamily of voltage-gated
      K(+) channels. The Kv2-catfish RNA was expressed in taste buds, brain, skeletal
      muscle, kidney, intestine and gills, and its gene is represented as a single copy
      in the catfish genome. Recombinant channels expressed in Xenopus oocytes were
      selective for K(+), and were inhibited by tetraethylammonium applied to the
      extracellular side of the membrane during two-electrode voltage clamp analysis
      with a 50% inhibitory constant of 6.1 mM. The channels showed voltage-dependent
      activation, and did not inactivate within 200 ms. Functionally, Kv2-catfish is a
      voltage-gated, delayed rectifier K(+) channel, and its primary structure is the
      most divergent sequence identified among the vertebrate members of the Kv2
      subfamily of K(+) channels, being related equally well to Kv2.1 and Kv2.2.

PMID- 11238732
TI  - Microglial secreted cathepsin B induces neuronal apoptosis.
AB  - Activated microglia release a number of substances that can influence neuronal
      signalling and survival. Here we report that microglia stimulated with the
      peptide chromogranin A (CGA), secreted the cysteine protease, cathepsin B.
      Conditioned medium from CGA exposed microglia was neurotoxic to the HT22
      hippocampal cell line and to primary cultures of cerebellar granule neurones. In
      both neuronal cell types, the neurotoxicity could be significantly attenuated
      with z-FA-fmk or by depletion of microglial conditioned medium with cathepsin B
      antibody. Conditioned medium from activated microglia or cathepsin B alone
      induced neuronal apoptosis and caspase 3 activation. Our data indicate that CGA
      activated microglia can trigger neuronal apoptosis and that this may be mediated
      through the secretion of cathepsin B. Since cathepsins may also play a role in
      the amyloidogenic processing of amyloid precursor protein, these results may have
      significance for tissue damage and neuronal loss in the neuropathology of
      Alzheimer's disease.

PMID- 11238730
TI  - Growth/differentiation factor 7 is preferentially expressed in the primary motor
      area of the monkey neocortex.
AB  - We applied a differential display PCR technique to isolate molecules that are
      area-specific in expression in the primate neocortex, and found that
      growth/differentiation factor 7 (GDF7), a member of the bone morphogenetic
      protein (BMP)/transforming growth factor (TGF) beta super-family, is
      preferentially expressed in the primary motor area of African green monkeys
      (Cercopithecus aethiops). We proved that GDF7 is 10 times more abundant in the
      motor cortex than in the visual cortex by northern blotting and quantitative RT
      PCR. When we examined the neocortex of closely related rhesus monkeys (Macaca
      mulatta), GDF7 was also most abundant in the motor cortex, although the regional
      difference was reduced to 3-fold. This differential expression pattern was
      observed in both newborn and infant rhesus monkeys. We found that several type
      I/II receptors of BMP, candidates of the receptors for GDF7, are uniformly
      expressed in the mature neocortex. The unique expression pattern of GDF7 suggests
      that it may play an active role in the motor area of the primate neocortex.

PMID- 11238733
TI  - Integrin signaling via the PI3-kinase-Akt pathway increases neuronal resistance
      to glutamate-induced apoptosis.
AB  - Integrins are integral membrane proteins that mediate adhesive interactions of
      cells with the extracellular matrix and with other cells. Integrin engagement
      results in activation of intracellular signaling cascades that effect several
      different cellular responses including motility, proliferation and survival.
      Although integrins are known to provide cell survival signaling in various types
      of non-neuronal cells, the possibility that integrins modulate neuron survival
      has not been explored. We now report data demonstrating a neuroprotective
      function of integrins in embryonic hippocampal neurons. Neurons grown on laminin,
      an integrin ligand, exhibit increased resistance to glutamate-induced apoptosis
      compared with neurons grown on polylysine. Neurons expressed integrin beta1 and
      treatment of cultures with an antibody against integrin beta1 abolished the
      protective effect of laminin. Neurons maintained on laminin exhibited a sustained
      activation of the Akt signaling pathway demonstrated in immunoblot analyses using
      an antibody that selectively recognizes phosphorylated Akt. The neuroprotective
      effect of integrin engagement by laminin was mimicked by an IKLLI-containing
      integrin-binding peptide and was abolished by treatment of neurons with the PI3
      kinase inhibitor wortmanin. Levels of the anti-apoptotic protein Bcl-2 were
      increased in neurons grown on laminin and decreased by wortmanin, suggesting a
      mechanism for the neuroprotective effect of integrin-mediated signaling. The
      ability of integrin-mediated signaling to prevent glutamate-induced apoptosis
      suggests a mechanism whereby neuron-substrate interactions can promote neuron
      survival under conditions of glutamate receptor overactivation.

PMID- 11238734
TI  - Signaling pathways in the induction of c-met receptor expression by its ligand
      scatter factor/hepatocyte growth factor in human glioblastoma.
AB  - Scatter factor/hepatocyte growth factor (SF/HGF) and its tyrosine kinase receptor
      c-met are developmentally expressed, neuroprotective, and tumorigenic within the
      CNS. In the present study SF/HGF is shown to induce the expression of c-met in
      two human glioblastoma cell lines, U-373 MG and T98G, and the signaling pathways
      involved in this induction are dissected. SF/HGF activated mitogen-activated
      protein kinase (MAPK) and inhibition of either Ras or MAPK-kinase completely
      inhibited SF/HGF-mediated c-met induction. Inhibition of phospholipase-C (PLC)
      did not affect c-met induction in either cell line. Inhibition of
      phosphoinositide 3-kinase (PI3-kinase) substantially reduced c-met induction by
      SF/HGF in T98G cells but had no effect in U-373 MG cells. Protein kinase C (PKC)
      inhibition reduced c-met induction in T98G cells but not in U-373 MG cells.
      SF/HGF induced the expression of c-fos and c-jun mRNA and increased the levels of
      AP-1 transcription factor in both cells lines as determined by AP-1-luciferase
      reporter expression. Transfection of either cell line with TAM-67, a dominant
      negative for the jun transactivation domain, completely inhibited AP-1 and c-met
      induction by SF/HGF. These results support a model of c-met induction by SF/HGF
      in human glioma cells that uniformly involves Ras, MAPK, and AP-1 and
      additionally involves PI3-kinase and PKC in some cell lines.

PMID- 11238735
TI  - Homocysteine potentiates copper- and amyloid beta peptide-mediated toxicity in
      primary neuronal cultures: possible risk factors in the Alzheimer's-type
      neurodegenerative pathways.
AB  - Oxidative stress may have an important role in the progression of
      neurodegenerative disorders such as Alzheimer's disease (AD) and prion diseases.
      Oxidative damage could result from interactions between highly reactive
      transition metals such as copper (Cu) and endogenous reducing and/or oxidizing
      molecules in the brain. One such molecule, homocysteine, a thiol-containing amino
      acid, has previously been shown to modulate Cu toxicity in HeLa and endothelial
      cells in vitro. Due to a possible link between hyperhomocysteinemia and AD, we
      examined whether interaction between homocysteine and Cu could potentiate Cu
      neurotoxicity. Primary mouse neuronal cultures were treated with homocysteine and
      either Cu (II), Fe (II or III) or Zn (II). Homocysteine was shown to selectively
      potentiate toxicity from low micromolar concentrations of Cu. The toxicity of
      homocysteine/Cu coincubation was dependent on the ability of homocysteine to
      reduce Cu (II) as reflected by the inhibition of toxicity with the Cu (I)
      specific chelator, bathocuproine disulphonate. This was supported by data showing
      that homocysteine reduced Cu (II) more effectively than cysteine or methionine
      but did not reduce Fe (III) to Fe (II). Homocysteine also generated high levels
      of hydrogen peroxide in the presence of Cu (II) and promoted Abeta/Cu-mediated
      hydrogen peroxide production and neurotoxicity. The potentiation of metal
      toxicity did not involve excitotoxicity as ionotropic glutamate receptor
      antagonists had no effect on neurotoxicity. Homocysteine alone also had no effect
      on neuronal glutathione levels. These studies suggest that increased copper
      and/or homocysteine levels in the elderly could promote significant oxidant
      damage to neurons and may represent additional risk factor pathways which
      conspire to produce AD or related neurodegenerative conditions.

PMID- 11238736
TI  - 5-HT(2A) and D(2) receptor blockade increases cortical DA release via 5-HT(1A)
      receptor activation: a possible mechanism of atypical antipsychotic-induced
      cortical dopamine release.
AB  - Atypical antipsychotic drugs (APDs), all of which are relatively more potent as
      serotonin (5-HT)(2A) than dopamine D(2) antagonists, may improve negative
      symptoms and cognitive dysfunction in schizophrenia, in part, via increasing
      cortical dopamine release. 5-HT(1A) agonism has been also suggested to contribute
      to the ability to increase cortical dopamine release. The present study tested
      the hypothesis that clozapine, olanzapine, risperidone, and perhaps other
      atypical APDs, increase dopamine release in rat medial prefrontal cortex (mPFC)
      via 5-HT(1A) receptor activation, as a result of the blockade of 5-HT(2A) and
      D(2) receptors. M100907 (0.1 mg/kg), a 5-HT(2A) antagonist, significantly
      increased the ability of both S:(-)-sulpiride (10 mg/kg), a D(2) antagonist
      devoid of 5-HT(1A) affinity, and R:(+)-8-OH-DPAT (0.05 mg/kg), a 5-HT(1A)
      agonist, to increase mPFC dopamine release. These effects of M100907 were
      abolished by WAY100635 (0.05 mg/kg), a 5-HT(1A) antagonist, which by itself has
      no effect on mPFC dopamine release. WAY100635 (0.2 mg/kg) also reversed the
      ability of clozapine (20 mg/kg), olanzapine (1 mg/kg), risperidone (1 mg/kg), and
      the R:(+)-8-OH-DPAT (0.2 mg/kg) to increase mPFC dopamine release. Clozapine is a
      direct acting 5-HT(1A) partial agonist, whereas olanzapine and risperidone are
      not. These results suggest that the atypical APDs via 5-HT(2A) and D(2) receptor
      blockade, regardless of intrinsic 5-HT(1A) affinity, may promote the ability of 5
      HT(1A) receptor stimulation to increase mPFC DA release, and provide additional
      evidence that coadministration of 5-HT(2A) antagonists and typical APDs, which
      are D(2) antagonists, may facilitate 5-HT(1A) agonist activity.

PMID- 11238737
TI  - Constitutive alpha-secretase cleavage of the beta-amyloid precursor protein in
      the furin-deficient LoVo cell line: involvement of the pro-hormone convertase 7
      and the disintegrin metalloprotease ADAM10.
AB  - The beta-amyloid precursor protein (betaAPP) undergoes a physiological cleavage
      triggered by one or several proteolytic activities referred to as alpha
      secretases, leading to the secretion of sAPPalpha. Several lines of evidence
      indicate that the alpha-secretase cleavage is a highly regulated process. Thus,
      besides constitutive production of sAPPalpha, several studies have reported on
      protein kinase C-regulated sAPPalpha secretion. Studies aimed at identifying
      alpha-secretase(s) candidates suggest the involvement of enzymes belonging to the
      pro-hormone convertases and disintegrin families. The delineation of respective
      contributions of proteolytic activities in constitutive and regulated sAPPalpha
      secretion is rendered difficult by the fact that the overall regulated response
      always includes the basal constitutive counterpart that cannot be selectively
      abolished. Here we report on the fact that the furin-deficient LoVo cells are
      devoid of regulated PKC-dependent sAPPalpha secretion and therefore represent an
      interesting model to study exclusively the constitutive sAPPalpha secretion. We
      show here, by a pharmacological approach using selective inhibitors, that pro
      hormone convertases and proteases of the ADAM (disintegrin metalloproteases)
      family participate in the production/secretion of sAPPalphas in LoVo cells.
      Transfection analysis allowed us to further establish that the pro-hormone
      convertase 7 and ADAM10 but not ADAM17 (TACE, tumour necrosis factor alpha
      converting enzyme) likely contribute to constitutive sAPPalpha secretion by LoVo
      cells.

PMID- 11238738
TI  - Phosphoinositide 3-kinase regulates crosstalk between Trk A tyrosine kinase and
      p75(NTR)-dependent sphingolipid signaling pathways.
AB  - The mechanism of crosstalk between signaling pathways coupled to the Trk A and
      p75(NTR) neurotrophin receptors in PC12 cells was examined. In response to nerve
      growth factor (NGF), Trk A activation inhibited p75(NTR)-dependent sphingomyelin
      (SM) hydrolysis. The phosphoinositide 3-kinase (PI 3-kinase) inhibitor, LY294002,
      reversed this inhibition suggesting that Trk A activation of PI 3-kinase is
      necessary to inhibit sphingolipid signaling by p75(NTR). In contrast, SM
      hydrolysis induced by neurotrophin-3 (NT-3), which did not activate PI-3 kinase,
      was uneffected by LY294002. However, transient expression of a constituitively
      active PI 3-kinase inhibited p75(NTR)-dependent SM hydrolysis by both NGF and NT
      3. Intriguingly, NGF induced an association of activated PI 3-kinase with acid
      sphingomyelinase (SMase). This interaction localized to caveolae-related domains
      and correlated with a 50% decrease in immunoprecipitated acid SMase activity. NGF
      stimulated PI 3-kinase activity was necessary for inhibition of acid SMase but
      was not required for ligand-induced association of the p85 subunit of PI 3-kinase
      with the phospholipase. Finally, this interaction was specific for NGF since EGF
      did not induce an association of PI 3-kinase with acid SMase. In summary, our
      data suggest that PI 3-kinase regulates the inhibitory crosstalk between Trk A
      tyrosine kinase and p75(NTR)-dependent sphingolipid signaling pathways and that
      this interaction localizes to caveolae-related domains.

PMID- 11238739
TI  - PC12 cells utilize the homophilic binding site of L1 for cell-cell adhesion but
      L1-alphavbeta3 interaction for neurite outgrowth.
AB  - Treatment of PC12 cells with nerve growth factor induces their differentiation
      into sympathetic neuron-like cells and the concomitant expression of the neural
      cell adhesion molecule L1, a member of the Ig superfamily. To investigate the
      mechanism of L1-stimulated neurite outgrowth in PC12 cells, substrate-immobilized
      fusion proteins containing different extracellular domains of L1 were assayed for
      their neuritogenic activity. Surprisingly, domain Ig2 of L1, which was previously
      found to contain both homophilic binding and neuritogenic activities, failed to
      promote neurite outgrowth. In contrast, L1-Ig6 stimulated neurite outgrowth from
      PC12 cells. Despite this, homotypic binding of PC12 cells was significantly
      inhibited by antibodies against L1-Ig2, indicating that L1-L1 binding contributed
      to the intercellular adhesiveness of PC12 cells, but L1-stimulated neurite
      outgrowth depends on heterophilic interactions. Thus, PC12 cells provide a
      valuable model for the study of these two distinct functions of L1. Mutagenesis
      of L1-Ig6 highlighted the importance of the Arg-Gly-Asp motif in this domain for
      neuritogenesis. Inhibition studies using cyclic Arg-Gly-Asp-containing peptide
      and anti-integrin antibodies suggested the involvement of alphavbeta3 integrin.
      Furthermore, neurite outgrowth stimulated by L1-Ig6 was inhibited by lavendustin
      A and the MEK inhibitor PD98059, suggesting a signaling pathway that involves
      tyrosine kinase activation and the mitogen-activated protein kinase cascade.

PMID- 11238740
TI  - Nurr1 enhances transcription of the human dopamine transporter gene through a
      novel mechanism.
AB  - The importance of the nuclear receptor nurr1 for the appropriate development of
      mesencephalic dopamine-synthesizing neurons has been clearly demonstrated through
      the targeted disruption of the nurr1 gene. The persistence of nurr1 expression in
      adult tissue suggests a possible role for this transcription factor in the
      maintenance, as well as development, of the dopaminergic phenotype. To address
      this issue, we analyzed the effects of nurr1 on the transcriptional expression of
      the human dopamine transporter gene (hDAT), one of the most specific phenotypic
      markers for dopaminergic neurons. Nurr1 enhanced the transcriptional activity of
      hDAT gene constructs transiently transfected into a newly described cell line
      (SN4741) that expresses a dopaminergic phenotype, whereas other members of the
      NGFI-B subfamily of nuclear receptors had lesser or no effects. Nurr1 activation
      of hDAT was not dependent upon heterodimerization with the retinoid X receptor.
      Unexpectedly, functional analysis of a series of gene constructs revealed that a
      region of the hDAT 5'-flanking sequence devoid of NGFI-B response element (NBRE)
      like sites mediated nurr1 activation. Additional experiments using a nurr1 mutant
      construct suggest that nurr1 activates hDAT transcription via a novel NBRE
      independent mechanism.

PMID- 11238741
TI  - Sphingosine kinase expression regulates apoptosis and caspase activation in PC12
      cells.
AB  - Sphingosine-1-phosphate (SPP), a bioactive sphingolipid metabolite, suppresses
      apoptosis of many types of cells, including rat pheochromocytoma PC12 cells.
      Elucidating the molecular mechanism of action of SPP is complicated by many
      factors, including uptake and metabolism, as well as activation of specific G
      protein-coupled SPP receptors, known as the endothelial differentiation gene-1
      (EDG-1) family. In this study, we overexpressed type 1 sphingosine kinase
      (SPHK1), the enzyme that converts sphingosine to SPP, in order to examine more
      directly the role of intracellularly generated SPP in neuronal survival. Enforced
      expression of SPHK1 in PC12 cells resulted in significant increases in kinase
      activity, with corresponding increases in intracellular SPP levels and
      concomitant decreases in both sphingosine and ceramide, and marked suppression of
      apoptosis induced by trophic factor withdrawal or by C(2)-ceramide. NGF, which
      protects PC12 cells from serum withdrawal-induced apoptosis, also stimulated
      SPHK1 activity. Surprisingly, overexpression of SPHK1 had no effect on activation
      of two known NGF-stimulated survival pathways, extracellular signal regulated
      kinase ERK 1/2 and Akt. However, trophic withdrawal-induced activation of the
      stress activated protein kinase, c-Jun amino terminal kinase (SAPK/JNK), and
      activation of the executionary caspases 2, 3 and 7, were markedly suppressed.
      Moreover, this abrogation of caspase activation, which was prevented by the SPHK
      inhibitor N,N-dimethylsphingosine, was not affected by pertussis toxin treatment,
      indicating that the cytoprotective effect was likely not mediated by binding of
      SPP to cell surface G(i)-coupled SPP receptors. In agreement, there was no
      detectable release of SPP into the culture medium, even after substantially
      increasing cellular SPP levels by NGF or sphingosine treatment. In contrast to
      PC12 cells, C6 astroglioma cells secreted SPP, suggesting that SPP might be one
      of a multitude of known neurotrophic factors produced and secreted by glial
      cells. Collectively, our results indicate that SPHK/SPP may play an important
      role in neuronal survival by regulating activation of SAPKs and caspases.

PMID- 11238743
TI  - Complete inhibition of in vivo glioma growth by oncostatin M.
AB  - We describe here the oncostatin M (OSM)-dependent inhibition of in vivo tumour
      formation after intracerebral inoculation of glioblastoma cells in mice. We
      generated human glioblastoma cells transfected with the OSM gene under the
      control of a tetracycline-response promoter. Upon removal of tetracycline from
      the medium, cells exhibited a differentiated cell morphology, while proliferation
      was significantly inhibited. After implantation of these cells into nude mice
      brains, large tumours developed in animals lacking OSM expression, whereas no
      tumour formation was observed in mice with induced OSM expression. Our results
      suggest that OSM exerts pronounced antitumorigenic effects on glioblastoma cells
      in vivo and provide arguments for a therapeutic application of OSM in humans.

PMID- 11238744
TI  - Depletion of glutathione up-regulates mitochondrial complex I expression in glial
      cells.
AB  - Glutathione deficiency is commonly associated with mitochondrial complex I
      dysfunction and loss of viability in neurones, but not in glia. In order to
      address the possible mechanism responsible for this cellular difference, the
      regulation of mitochondrial complex I expression by glutathione depletion was
      investigated in glial cells. Incubation of rat-cultured astrocytes and C6 glioma
      cells with the specific gamma-glutamylcysteine synthetase inhibitor L-buthionine
      (S:,R:)-sulfoximine (L-BSO; 0.1-1 mM) decreased the total specific content of
      glutathione in a dose- and time-dependent fashion. Northern blot analyses
      revealed that glutathione deficiency caused by L-BSO (0.1 mM) was associated with
      a twofold enhancement in complex I regulatory subunit ND6 (mitochondrially
      encoded) mRNA expression after 24-72 h. This effect was accompanied by a twofold
      increase in complex-I activity at 72 h in L-BSO-treated cells, as compared with
      control cells, but complex II-III, complex IV and citrate synthase activities
      were unaltered. It is suggested that the oxidative stress caused by glutathione
      depletion in glial cells would up-regulate complex-I activity by enhancing the
      expression of the mitochondrially encoded regulatory subunit. These results could
      offer further insight into the different degree of cellular susceptibility
      observed in glial vs. neuronal cells against oxidative stress.

PMID- 11238742
TI  - Galpha(olf) is necessary for coupling D1 and A2a receptors to adenylyl cyclase in
      the striatum.
AB  - In the brain, dopamine and adenosine stimulate cyclic AMP (cAMP) production
      through D1 and A2a receptors, respectively. Using mutant mice deficient in the
      olfactory isoform of the stimulatory GTP-binding protein alpha subunit,
      Galpha(olf), we demonstrate here the obligatory role of this protein in the
      adenylyl cyclase responses to dopamine and adenosine in the caudate putamen.
      Responses to dopamine were also dramatically decreased in the nucleus accumbens
      but remained unaffected in the prefrontal cortex. Moreover, in the caudate
      putamen of mice heterozygous for the mutation, the amounts of Galpha(olf) were
      half of the normal levels, and the efficacy of dopamine- and CGS 21680 A(2)
      agonist-stimulated cAMP production was decreased. Together, these results
      identify Galpha(olf) as a critical parameter in the responses to dopamine and
      adenosine in the basal ganglia.

PMID- 11238745
TI  - Rapid transferrin efflux from brain to blood across the blood-brain barrier.
AB  - The brain efflux index method is used to examine the extent to which transferrin
      effluxes from brain to blood across the blood-brain barrier (BBB) following
      intracerebral injection. Whereas high-molecular-weight dextran is nearly 100%
      retained in brain for up to 90 min after intracerebral injection in the Par2
      region of the parietal cortex of brain, there is rapid efflux of transferrin from
      brain to blood across the BBB. The efflux of apotransferrin is 3.5-fold faster
      than the efflux of holo-transferrin. The brain to blood efflux of apotransferrin
      is completely saturable by unlabeled transferrin, but is not inhibited by other
      plasma proteins. These studies provide evidence for reverse transcytosis of
      transferrin from brain to blood across the BBB. As circulating transferrin is
      known to undergo transcytosis across the BBB in the blood-to-brain direction,
      these studies support the model of bidirectional transcytosis of transferrin
      through the BBB in vivo.

PMID- 11238746
TI  - Function of vitamin A in vertebrate embryonic development.
AB  - Advances in molecular biology and retinoic acid receptor research have
      significantly contributed to the understanding of the role of vitamin A during
      vertebrate development. Examination of the function of this vitamin during very
      early developmental stages using the completely vitamin A-depleted avian embryo
      has revealed that the vitamin A requirement begins at the time of formation of
      the primitive heart, circulation and specification of hindbrain. The lack of
      vitamin A at this critical time results in gross abnormalities and early
      embryonic death. In rodent models, vitamin A deficiency can be targeted to later
      gestational windows and documents the need for vitamin A for more advanced stages
      of development. Major target tissues of vitamin A deficiency include the heart,
      central nervous system and structures derived from it, the circulatory,
      urogenital and respiratory systems, and the development of skull, skeleton and
      limbs. These abnormalities are also evident in mice mutants from retinoid
      receptor knockouts; they have revealed both morphological and molecular aspects
      of vitamin A function during development. Retinoic acid receptors (RAR) in
      partnership with retinoid X receptor (RXR)alpha appear to be the important
      retinoid receptor transcription factors regulating vitamin A function at the gene
      level during development via the physiologic ligand all-trans-retinoic acid.
      Homeostasis of retinoic acid is maintained by developmentally regulated vitamin A
      metabolism enzyme systems. Inadequate vitamin A nutrition during early pregnancy
      may account for some pediatric congenital abnormalities.

PMID- 11238748
TI  - Franklin Church Bing (1902-1988).

PMID- 11238747
TI  - Glucagon-like peptide 2: a nutrient-responsive gut growth factor.
AB  - Glucagon-like peptide 2 (GLP-2) is a 33-amino acid peptide derived from the
      tissue-specific, post-translational processing of the proglucagon gene expressed
      in the intestinal enteroendocrine L-cell. The primary stimulus for GLP-2
      secretion is nutrient intake, and involves direct luminal stimulation of the L
      cell as well as indirect enteroendocrine and neural mechanisms. The biological
      activity of GLP-2 in circulation is regulated by the proteolytic cleavage of the
      N-terminus by dipeptidylpeptidase IV. Several studies have shown that GLP-2 has
      specific trophic effects on the small and large intestine, which are mediated by
      stimulation of cell proliferation and inhibition of apoptosis and proteolysis.
      GLP-2 also has been shown to suppress gastric motility and acid secretion,
      increase hexose transport activity and suppress food intake, specifically when
      infused centrally. The actions of GLP-2 are mediated by a G-protein-linked,
      membrane receptor (GLP-2R) that is localized largely to the gastrointestinal
      tract, but also is found in the brain. The secretion of GLP-2 and expression of
      the GLP-2R are present in the late gestation fetus. However, the developing
      intestine does not become responsive to the trophic effect of GLP-2 until after
      birth. Based on its efficacy in preventing atrophy and stimulating growth in the
      neonatal gut, GLP-2 may be a promising therapeutic adjuvant for treatment of
      infants with compromised gut function.

PMID- 11238749
TI  - Phosphatidylcholine inhibits and lysophosphatidylcholine enhances the lymphatic
      absorption of alpha-tocopherol in adult rats.
AB  - This study was conducted to compare the effects of enterally infused
      phosphatidylcholine (PC) and lysophosphatidylcholine (lysoPC) on the lymphatic
      absorption of alpha-tocopherol (alphaTP) in male rats. In expt. 1, bile-diverted
      rats with mesenteric lymph cannulas were infused at 3.0 mL/h for 8 h with a lipid
      emulsion containing 5.0 micromol alphaTP, 565 micromol 14C-triolein (14C-OA) and
      396 micromol Na+-taurocholate with 80 micromol 1,2-dipalmitoyl PC (DPPC) or 1,2
      dilinoleoyl PC (DLPC) or without PC (NoPC) in 24 mL phosphate-buffered saline (pH
      6.6). In expt. 2, the effects of 1,2-dioleoyl PC (DOPC) and 1-oleoyl-2-hydroxy-PC
      (lysoPC) on alphaTP and 14C-cholesterol absorption were compared in rats with
      lymph cannulas. When DPPC or DLPC was infused, the lymphatic absorption of
      alphaTP was lowered drastically. The cumulative absorptions of alphaTP in rats
      infused with DPPC and DLPC were 45 and 52%, respectively, of the control values
      (NoPC). No significant difference was noted between the PC groups. In contrast,
      the absorption of 14C-OA was increased by 42 to 43% in rats infused with DPPC or
      DLPC compared with that in NoPC rats. Phospholipid outputs also were
      significantly higher in DPPC (34.0 +/- 5.5 micromol /8 h) and DLPC (32.4 +/- 2.4
      micromol /8 h) rats than in NoPC rats (21.2 +/- 4.2 micromol /8 h). When lysoPC
      was infused, the absorptions of alphaTP and 14C-cholesterol were increased
      markedly compared with those for DOPC, with no significant difference in PL
      output between groups infused with DOPC and lysoPC. These observations provide
      clear evidence that PC present in a lipid emulsion inhibits alphaTP absorption,
      whereas it enhances the absorption of fat. The data also demonstrate that lysoPC
      simultaneously increases the absorption of alphaTP and cholesterol. The findings
      indicate that luminal PC inhibits the absorption of alphaTP and that hydrolysis
      of PC is critical to improving the intestinal absorption of the vitamin.

PMID- 11238750
TI  - Soybean isoflavones dose-dependently reduce bone turnover but do not reverse
      established osteopenia in adult ovariectomized rats.
AB  - We assessed the dose-dependent effects of daily soybean isoflavone (IF)
      consumption in reversing bone loss in adult ovariectomized rats. On d 0, female
      Wistar rats (7 mo old; n = 55) were either sham-operated (SH; n = 14) or
      ovariectomized (n = 41). On d 80, intermediate rats (SH: n = 5; ovariectomized: n
      = 5) were killed to confirm the ovariectomy-induced bone loss. The remaining
      ovariectomized rats were randomly assigned to one of four groups of nine rats
      each and fed soybean IF (mixed with a soy protein-free semipurified diet) at 0
      (OVX), 20 (IF20), 40 (IF40) or 80 (IF80) mg/(kg body. d) for 84 d.
      Simultaneously, SH rats were fed the semipurified diet without any additional
      compound and killed on d 164, as were the other rats. As expected, both bone
      mineral density in the total femur and in its diaphyseal and metaphyseal
      subregions and cancellous bone area/measured surface in the distal femur
      metaphysis were lower in OVX than in SH rats (P: < 0.05). OVX rats had higher
      plasma osteocalcin concentration and urinary deoxypyridinoline excretion than SH
      rats (P: < 0.05). On d 164, osteocalcin and deoxypyridinoline concentrations were
      lower in IF40 or IF80 rats than in OVX rats (P: < 0.05). Nevertheless, neither
      bone mineral density nor cancellous bone area was greater in IF-fed rats than in
      OVX rats. Therefore, in adult ovariectomized rats, daily soybean IF consumption
      decreased bone turnover but did not reverse established osteopenia.

PMID- 11238751
TI  - Secretion of trophic gut peptides is not different in bolus- and continuously fed
      piglets.
AB  - In neonates, bolus feeding is associated with greater rates of intestinal growth
      than is continuous feeding. We tested whether the concentrations and secretion
      rates of trophic gut peptides are higher in bolus-fed than in continuously fed
      piglets. Five 21-d-old piglets were surgically implanted with gastric, arterial
      and portal catheters and a portal blood flow probe. At postnatal d 30 and 31,
      pigs received an equal amount of primed continuous or bolus feeding of a cow's
      milk formula in a randomized, crossover design. During a 6-h period, portal blood
      flow and arterial and portal concentrations of glucagon-like peptide-2 (GLP-2),
      peptide YY (PYY) and gastric inhibitory polypeptide (GIP) were measured. All
      hormone levels were significantly increased within 1 h of the start of the
      experiment, independent of the feeding modality. There were no differences
      between bolus and continuous feeding in either the arterial concentrations or
      secretion rates of GLP-2, PYY and GIP. In both treatment groups, the increases in
      the plasma concentrations of GLP-2 and GIP after feeding were substantially
      greater than those for PYY. We conclude that the production or circulating
      concentrations of GLP-2, PYY and GIP are not significantly different in bolus-
      and primed continuously fed piglets.

PMID- 11238752
TI  - Folate status during pregnancy in women is improved by long-term high vegetable
      intake compared with the average western diet.
AB  - The effect of increasing dietary folate on folate status during pregnancy is
      controversial. The aim of this study was to compare folate intake and folate
      status during pregnancy of women with high long-term vegetable intake and those
      eating an average Western diet. In a prospective study that included 109
      participants, pregnant women adhering to a predominant vegetarian diet with high
      vegetable intake for 8 +/- 0.5 y with subgroups of ovo-lacto vegetarians (n = 27)
      and low meat eaters (n = 43) and women eating an average Western diet (control
      group, n = 39) were compared with regard to dietary intake and plasma and red
      blood cell (RBC) folate concentrations during wk 9-12, 20-22 and 36-38 of
      gestation. Plasma and RBC folate concentrations were highest in ovo-lacto
      vegetarians, followed by low meat eaters and lowest in the controls. Ovo-lacto
      vegetarians and low meat eaters showed a lower risk for folate deficiency, with
      RBC folate concentrations of <320 nmol/L resulting in odds ratios of 0.10 (95%
      confidence interval, 0.01-0.56) and 0.52 (95% confidence interval, 0.20-1.34),
      respectively. In ovo-lacto vegetarians, the RBC folate concentration was
      positively related to the intake of vitamin B-12 (r = 0.51, P: < 0.0001). The
      results of the study suggest that long-term high vegetable intake favorably
      affects plasma folate as well as RBC folate concentrations throughout pregnancy
      and reduces the risk of folate deficiency if an adequate vitamin B-12 supply is
      ensured.

PMID- 11238753
TI  - Wheat bran and soy protein feeding do not alter urinary excretion of the
      isoflavan equol in premenopausal women.
AB  - The capacity to convert the soy isoflavone daidzein to equol in vivo is
      presumably determined by an individual's intestinal microfloral populations;
      however, diet may also influence this conversion. The objectives of the present
      study were to determine whether a 1-mo supplementation of dietary fiber as wheat
      bran increases urinary equol excretion in equol excreters and stimulates equol
      production in nonexcreters and whether longer-term soy isoflavone intake
      increases equol production or alters overall urinary isoflavone excretion. First,
      we screened 74 women, ages 20-40 y, and determined their equol-excreter status.
      In these women, health and lifestyle patterns and habitual dietary intake did not
      differ according to equol-excreter status. Next, 26 of the women (13 equol
      excreters and 13 nonexcreters) were assigned (blocked on equol-excreter status)
      to either longer-term (1 mo) or short-term (4 d) soy protein supplementation.
      Within each soy treatment group, women participated in two 1-mo intervention
      periods (the exact length was determined by each woman's menstrual cycle) during
      which they consumed their usual diets supplemented daily with either 0 or 16 g
      dietary fiber in a randomized crossover design. A 1-mo washout period separated
      the two diet periods. Among the 19 women who completed both periods, fiber
      supplementation did not increase equol production in equol excreters or
      nonexcreters. In addition, isoflavonoid excretion did not differ by fiber dose or
      length of soy intervention. These results suggest that a daily 16 g-fiber dose as
      wheat bran and the addition of soy protein do not alter significantly the
      capacity of colonic microflora to produce equol.

PMID- 11238754
TI  - Red wine is a poor source of bioavailable flavonols in men.
AB  - Red wine is a source of polyphenolic antioxidants, of which flavonols such as
      quercetin are representatives. Red wine might therefore prevent LDL oxidation and
      atherosclerosis. However, data on the bioavailability of flavonols from wine are
      lacking. Therefore, we compared the bioavailability of flavonols, especially
      quercetin, from red wine with that from the major dietary sources, yellow onions
      and black tea. Twelve healthy men consumed 750 mL red wine, 50 g fried onions or
      375 mL of black tea, each for 4 d in random order. These supplements provided
      similar amounts of quercetin (14-16 mg). There was a washout period of 3 d
      between each period of supplementation. The plasma quercetin concentration after
      the consumption of wine was lower than that after onions (P: < 0.05) and not
      different from that after tea. Urinary excretion of quercetin after wine did not
      differ from that after onions and was higher than that after tea (P: < 0.05). We
      conclude that flavonols from red wine are absorbed. However, because one glass of
      red wine provides fewer available flavonols than one portion of onions or one
      glass of tea, red wine appears to be a poorer source of flavonols than these
      other two sources.

PMID- 11238755
TI  - An assessment of various household food security measures in Hawaii has
      implications for national food security research and monitoring.
AB  - The Core Food Security Module (CFSM), the national food security monitoring tool,
      requires three affirmative responses to categorize households as food insecure.
      If this tool is unreliable or inaccurate, vulnerable segments of our population
      may be adversely affected. The objectives of the present study were to assess the
      credibility of applying the CFSM categorical measure to a population sample from
      Hawaii and to assess the concurrent validity of the CFSM, the new face-valid
      measure and measures adapted from the Radimer/Cornell (RC) measure and Community
      Childhood Hunger Identification Project. The sample included 1469 respondents
      gathered through a statewide telephone sample and 144 food pantry recipients.
      Responses to the 18 CFSM questions were used to create all four measures. The
      credibility of the CFSM categorical measure was also assessed via comparisons
      with individual items and with the 1995 national modal CFSM response pattern.
      Categorical measures were compared across food security prevalence estimates and
      indices of income and vegetable intake and with the CFSM scale measure.
      Differences in the modal response pattern between samples affected CFSM
      categorization. Only 36% of households followed the Hawaii modal response
      pattern, and categorization was not consistent with the content of key items.
      Although 85% of the households were classified as food secure by the CFSM, only
      78% were classified as food secure with each of the other food security measures.
      Concurrent validity of all measures was confirmed. A reassessment of the national
      CFSM categorical measure appears warranted.

PMID- 11238756
TI  - Dietary intakes and socioeconomic factors are associated with the hemoglobin
      concentration of Bangladeshi women.
AB  - Iron deficiency anemia affects a large number of women in developing countries,
      especially during child-bearing years. The hemoglobin concentration is useful for
      identifying iron deficiency anemia. The main objectives of this study were,
      first, to extend algorithms for calculating bioavailable iron from mixed diets,
      taking into account the enhancers and inhibitors of iron absorption under
      alternative assumptions on body iron stores. Second, a comprehensive longitudinal
      model was developed for the proximate determinants of hemoglobin concentration
      that included the subjects' dietary intakes, nutritional status, morbidity and
      socioeconomic factors and the unobserved between-subject differences. The model
      for hemoglobin concentration was estimated using three repeated observations on
      514 free living women in Bangladesh. Socioeconomic factors affecting the iron
      intake from meat, fish and poultry and from all animal sources were also modeled.
      The main results were that bioavailable iron, women's height and mid upper arm
      circumference and intake of iron tablets were significant predictors of
      hemoglobin concentration. Increases in household incomes were associated with
      higher intake of iron from meat, fish and poultry and from all animal sources.
      The algorithms for estimating bioavailable iron showed the importance of
      assumptions regarding body iron stores and underscored the need to develop
      suitable algorithms for subjects in developing countries.

PMID- 11238757
TI  - Understanding needs is important for assessing the impact of food assistance
      program participation on nutritional and health status in U.S. elderly persons.
AB  - This study aimed to assess the impact of food assistance programs on nutritional
      and health status of nutritionally needy elderly persons. Two cross-sectional and
      one longitudinal data sets were used: Third National Health and Nutrition
      Examination Survey (1988-94), Nutrition Survey of the Elderly in New York State
      (1994) and Longitudinal Study of Aging (1984-1990). Multiple logistic and linear
      regression analyses were used to examine whether food assistance participants
      among food insecure elderly (i.e., those whose needs for food assistance programs
      are met) have better nutrient intake, skinfold thickness and self-reported health
      status and less nutritional risk, hospitalization and mortality than
      nonparticipants (i.e., those whose needs are unmet) and whether the benefit is
      larger than that among food secure elderly persons. Across three data sets, food
      insecure elderly persons had poorer nutritional and health status than food
      secure elderly persons. Contrary to the hypotheses, among food insecure elderly
      persons, food assistance participants had similar or poorer nutrient intakes,
      skinfold thickness, nutritional risk, self-reported health status,
      hospitalization and mortality than nonparticipants. Food secure participants had
      similar nutritional and health status as food secure nonparticipants. Lack of
      information on the dynamic nature and changes in needs with program participation
      in the three data sets likely did not allow accurate estimation of the impact of
      food assistance participation. Different study designs, as well as theory and
      knowledge of needs that clarifies need status and its change within each older
      individual across an appropriate time interval, are necessary to accurately
      assess impacts of food assistance programs.

PMID- 11238758
TI  - Serum albumin binds beta- and alpha-monoolein in vitro.
AB  - We investigated the interaction of bovine serum albumin (BSA) and monoolein (MO)
      and estimated the number of BSA binding sites for the alpha- and beta-isomers of
      MO. The turbidity of increasing concentrations of aqueous dispersions of alpha-MO
      and beta-MO in the presence and absence of BSA was measured in triplicate by
      absorption spectrophotometry. Aqueous dispersions of [13C(1)]MO and
      [13C(1)]MO/BSA mixtures at molar ratios of 1:1, 3:1 and 5:1 were analyzed in
      duplicate by [13C]nuclear magnetic resonance (NMR) at pH 7.4 and 36 degrees C.
      BSA bound significantly more beta-MO than alpha-MO at 15 min: 5.4 +/- 0.42 and
      3.3 +/- 0.60 mol MO/mol BSA, respectively (P: < 0.05). [13C]NMR spectra of the
      1:1 molar ratio of [13C(1)]MO /BSA exhibited a single carbonyl peak at 175.19
      ppm, whereas spectra of 3:1 and 5:1 molar ratios exhibited three peaks between
      172 and 174 (ppm), each distinct from carbonyl resonances of either [13C(1)]MO
      dispersed in water, 176.72 (ppm) or BSA alone. The intensities of individual
      peaks, but not their chemical shift values, varied between 3:1 and 5:1 molar
      ratios, indicating that BSA has at least three MO binding sites and may bind up
      to five molecules of MO per molecule. This study confirms that serum albumin
      binds MO in vitro and supports the theory that albumin transports monoglycerides
      produced by lipoprotein lipase hydrolysis of triglyceride.

PMID- 11238759
TI  - Chronic but not acute energy restriction increases intestinal nutrient transport
      in mice.
AB  - Chronic energy restriction (ER) dramatically enhances intestinal absorption of
      nutrients by aged mice. Do adaptations in nutrient absorption develop only after
      extended ER or immediately after its initiation? To determine the time course of
      adaptations, we measured rates of intestinal glucose, fructose and proline
      transport 1-270 d after initiation of ER (70% of ad libitum) in 3-mo old mice.
      Mice of the same age that consumed food ad libitum (AL) served as controls; a
      third group was starved for 1 or 2 d only, to distinguish the effects of acute ER
      from those of starvation. Acute ER of 1, 2 and 10 d had no effect on nutrient
      absorption. Starvation significantly decreased intestinal mass per centimeter,
      thereby reducing transport per centimeter and intestinal absorptive capacity
      without significantly altering transport per milligram of intestine. ER for 24 d
      enhanced only fructose uptake, whereas ER for 270 d enhanced uptake of all
      nutrients by 20-100%. Despite marked differences in body weights, the wet weights
      of the stomach, small intestine, cecum and large intestine were generally similar
      in AL and ER mice, suggesting that the gastrointestinal tract was spared during
      ER. In contrast, the wet weights of the lungs, kidneys, spleen, heart, pancreas
      and liver each differed by 40-120% between ER and AL mice. Intestinal transport
      adaptations develop gradually during ER, and the main mechanism underlying these
      adaptations is a dramatic increase in transport activity per milligram tissue.

PMID- 11238760
TI  - Dietary fructooligosaccharides modify intestinal bioavailability of a single dose
      of genistein and daidzein and affect their urinary excretion and kinetics in
      blood of rats.
AB  - The influence of dietary fructooligosaccharides (FOS) on bioavailability of
      genistein and daidzein in rats was estimated by measuring their concentrations in
      plasma collected from three different veins and in urine after a single
      intragastric administration of isoflavone conjugates. Sprague-Dawley male rats (6
      wk old, n = 22) were fed a purified control (AIN-93G) diet or a FOS diet (AIN-93G
      + 5% FOS) for 7 d. A single dose of soy isoflavone conjugates, i.e., 8.5 mg as
      genistein and 33 mg as daidzein/kg body, was administered via a stomach tube at d
      5. Blood samples were collected after administration via catheters in the portal
      and central veins and by puncture of the tail vein. The isoflavones in plasma and
      urine were analyzed by time-resolved fluoroimmunoassay. The genistein
      concentration in the portal blood increased rapidly, reaching a peak of 3.5
      micromol/L in both groups at 1 h after administration. The concentrations in the
      central and tail venous blood were approximately half of those in the portal
      blood. In the FOS-fed group, both genistein and daidzein remained detectable at
      24 and 48 h in the tail venous plasma. The urinary excretion of both isoflavones
      in the 24- to 48-h period after administration was significantly higher in the
      FOS-fed group than in the control group. The difference between the portal and
      central veins indicated hepatic uptake, probably leading to conjugation of
      aglycones and excretion into bile. FOS modified the absorption and enterohepatic
      recirculation of isoflavones.

PMID- 11238761
TI  - L-arabinose feeding prevents increases due to dietary sucrose in lipogenic
      enzymes and triacylglycerol levels in rats.
AB  - L-Arabinose is a natural, poorly absorbed pentose that selectively inhibits
      intestinal sucrase activity. To investigate the effects of L-arabinose feeding on
      lipogenesis due to its inhibition of sucrase, rats were fed 0-30 g sucrose/100 g
      diets containing 0-1 g L-arabinose/100 g for 10 d. Lipogenic enzyme activities
      and triacylglycerol concentrations in the liver were significantly increased by
      dietary sucrose, and arabinose significantly prevented these increases. Arabinose
      feeding reduced the weights of epididymal adipose tissue. Moreover, plasma
      insulin and triacylglycerol concentrations were significantly reduced by dietary
      L-arabinose. These findings suggest that L-arabinose inhibits intestinal sucrase
      activity, thereby reducing sucrose utilization, and consequently decreasing
      lipogenesis.

PMID- 11238762
TI  - Olive oil prevents the adverse effects of dietary conjugated linoleic acid on
      chick hatchability and egg quality.
AB  - Dietary conjugated linoleic acid (CLA) decreases yolk 18:1(n-9), induces chick
      embryonic mortality and alters egg quality. A study was conducted to determine
      whether olive oil would prevent these adverse effects of CLA. Hens (15 per
      treatment) were fed diets containing 0.5 g corn oil/100 g (CO), 0.5 g CLA/100 g
      (CLA), 0.5 g corn oil plus 10 g olive oil/100 g (CO + OO) or 0.5 g CLA plus 10 g
      olive oil/100 g (CLA + OO). After 74 d of feeding, hens were placed on CO for 10
      d. Hens were artificially inseminated weekly. For hatchability studies, fertile
      eggs were collected daily, stored at 15 degrees C for 24 h and then incubated.
      After 6 d of feeding, embryonic mortality rates were 15, 100, 8 and 16% in the
      CO, CLA, CO + OO and CLA + OO groups, respectively. When CLA-fed hens were fed
      the CO diet, hatchability improved to that of the CO group within 7 d. For fatty
      acid analysis, three eggs were obtained at the 7 d of feeding. Relative CLA
      levels of yolk from CO-, CLA-, CO + OO- and CLA + OO-fed hens were 0.11 +/- 0.01,
      1.91 +/- 0.16, 0.08 +/- 0.04 and 0.69 +/- 0.07 g/100 g fatty acids, respectively.
      The ratios of 16:0/16:1(n-7) and 18:0/18:1(n-9) of yolk from CLA-fed hens were
      approximately 1- and approximately 1.5-fold greater, respectively, compared with
      those fed CO. OO prevented CLA-induced increases in 16:0 and 18:0 and the
      decrease in 18:1(n-9) in yolk. Fertile eggs were stored at 4 degrees C for 2 or
      10 wk and analyzed for pH or mineral levels. Dietary CLA caused abnormal pH
      changes of albumen and yolk when eggs were stored at 4 degrees C. The pH of yolk
      and albumen from CO-fed hens after 10 wk of storage was 6.12 +/- 0.12 and 9.06 +/
      0.03, respectively, versus 7.89 +/- 0.25 and 8.32 +/- 0.16, respectively, in
      eggs from CLA-fed hens. OO prevented CLA-induced abnormal changes in the pH of
      albumen and yolks. Eggs from CLA-fed hens had greater iron, calcium and zinc
      concentrations and lower magnesium, sodium and chloride concentrations in albumen
      relative to those from hens fed CO. OO prevented CLA-induced mineral exchange
      between yolk and albumen, presumably by reducing the yolk saturated fatty acids,
      which are believed to disrupt the vitelline membrane during cold storage. This
      study suggests that the adverse effects of CLA may be due to the increased level
      of saturated fatty acids. However, because the addition of olive oil also lowered
      egg CLA content, the direct role of egg CLA on egg hatchability and quality
      cannot be ruled out.

PMID- 11238763
TI  - Kefir milk enhances intestinal immunity in young but not old rats.
AB  - The adjuvant effect of kefir fermented milk on the mucosal and systemic immune
      systems was examined in young (6 mo old) and old (26 mo old) rats. Kefir-fed rats
      consisted of young or old rats consuming kefir-fermented milk ad libitum on a
      daily basis in addition to the standard diet, for 28 d. Control rats consumed
      only the standard diet. The rats were immunized intraduodenally with cholera
      toxin (CT) on d 7 and 21 and killed on d 28. The nonspecific serum immunoglobulin
      (Ig)A titers in kefir-fed and control rats did not differ in either age group.
      The serum anti-CT IgA antibody concentrations were significantly higher in the
      kefir-fed young rats compared with their age-matched controls (+86%, P: < or =
      0.05). This difference was associated with enhanced in vitro antibody secretion
      by cultured lymphocytes isolated from the Peyer's patches and the intestinal
      lamina propria (+180%, P: < or = 0.05). These enhanced responses were found only
      in the young rats. However, the nonspecific serum IgG titer was higher (>120%, P:
      < or = 0.05) and the anti-CT IgG titer was lower (-80%, P: < or = 0.05), in both
      young and old kefir-fed rats compared with their respective controls.
      Nevertheless, these results demonstrate that a kefir-supplemented diet affects
      the intestinal mucosal and systemic immune responses to intraduodenal CT
      differently in young and old rats. Most importantly, our data suggest that orally
      administered kefir enhances the specific intestinal mucosal immune response
      against CT in young adult, but not in senescent rats.

PMID- 11238765
TI  - Energy restriction does not alter bone mineral metabolism or reproductive cycling
      and hormones in female rhesus monkeys.
AB  - Energy restriction (ER) extends the life span and slows aging and age-related
      diseases in short-lived mammalian species. Although a wide variety of
      physiological systems have been studied using this paradigm, little is known
      regarding the effects of ER on skeletal health and reproductive aging. Studies in
      rhesus monkeys have reported that ER delays sexual and skeletal maturation in
      young male monkeys and reduces bone mass in adult males. No studies have examined
      the chronic effects on bone health and reproductive aging in female rhesus
      monkeys. The present cross-sectional study examined the effects of chronic (6 y)
      ER on skeletal and reproductive indices in 40 premenopausal and perimenopausal (7
      27 y old) female rhesus macaques (Macaca mulatta). Although ER monkeys weighed
      less and had lower fat mass, ER did not alter bone mineral density, bone mineral
      content, osteocalcin, 25-hydroxyvitamin D, 1,25-hydroxyvitamin D or parathyroid
      hormone concentrations, menstrual cycling or reproductive hormone concentrations.
      Body weight and lean mass were significantly related to bone mineral density and
      bone mineral content at all skeletal sites (total body, lumbar spine, mid and
      distal radius; P: < or = 0.04). The number of total menstrual cycles over 2 y, as
      well as the percentage of normal-length cycles (24-31 d), was lower in older than
      in younger monkeys (P: < or = 0.05). Older monkeys also had lower estradiol (P: =
      0.02) and higher follicle-stimulating hormone (P: = 0.02) concentrations than did
      younger monkeys. We conclude that ER does not negatively affect these indices of
      skeletal or reproductive health and does not alter age-associated changes in the
      same variables.

PMID- 11238764
TI  - A pancreatic extract-enriched diet improves the nutritional status of aged rats.
AB  - Correction of the malnourished state, particularly common and severe in elderly
      people, is often unsuccessful. To improve the efficiency of realimentation, we
      evaluated the nutritional effect of a pancreatic extract (PE)-enriched diet in
      malnourished aged rats. Sprague-Dawley male rats were randomly assigned to 6
      groups as follows: 1 group of control rats had free access to the diet for 12 wk
      (C group) and 5 groups were 50% food restricted for the same period. One food
      restricted group was then killed (R group) and the 4 remaining groups were refed
      for 1 wk using a standard diet enriched either with two different doses of a
      pancreatic extract (2.4 or 4.8 g/d in PE1 and PE2 groups, respectively) or with
      an isonitrogenous casein hydrolysate (CH1 and CH2 groups, respectively). Profound
      alterations induced by food restriction (FR) were moderately corrected by
      refeeding, except nitrogen balance, which was reestablished in rats refed all
      diets (P: < 0.01 vs. R). Supplementation of the food ration with a pancreatic
      extract clearly improved recovery. Indeed, body weight gain, both jejunal and
      ileal trophicity [jejunum: total height, PE2: 849 +/- 45 microm vs. CH2: 768 +/-
      17 microm (P: < 0.05); protein content, PE2: 69.9 +/- 5.7 mg vs. CH2: 56.4 +/-
      4.8 mg (P: < 0.01)] and nonspecific immune response in terms of H2O2 production
      by polymorphonuclear neutrophils and tumor necrosis factor alpha (TNF-alpha) by
      macrophages (PE2, 20.7 +/- 4.7 vs. CH2, 8.7 +/- 2.3, P: < 0.05) were improved in
      rats fed PE2. A pancreatic extract could improve the efficiency of realimentation
      in malnourished aged rats.

PMID- 11238766
TI  - Fatty acid composition of adipose tissue and serum lipids are valid biological
      markers of dairy fat intake in men.
AB  - The fatty acid intake is in part reflected by the fatty acid composition of
      adipose tissue and serum lipids. We evaluated whether the proportions of myristic
      (14:0), pentadecanoic (15:0) and heptadecanoic (17:0) fatty acids in the adipose
      tissue triacylglycerols and serum cholesterol esters and phospholipids reflect
      long-term dairy fat consumption in free-living men. In 114 healthy men aged 40-76
      y, we compared the relative content of 14:0, 15:0 and 17:0 in subcutaneous
      adipose tissue and in serum lipids with relative intake (g/100 g of total fat)
      assessed by two 1-wk weighed food records made 6 mo apart and assessed by
      fourteen 24-h dietary recall interviews equally distributed during 1 y. According
      to food records, the mean +/- SD dairy fat intake was 24.9 +/- 13.1 g/d (29.6 +/-
      10.5 g/100 g total fat); intake of 14:0, 15:0 and 17:0 was 4.6, 0.23 and 0.16
      g/100 g total fat, and the content in adipose tissue was 3.6, 0.36 and 0.25 g/100
      g fatty acids, respectively. Pearson correlation coefficients between intake of
      dairy fat (based on 24-h recalls) and fatty acid composition of adipose tissue
      were 0.64 (P: < 0.001) for 14:0, 0.74 (P: < 0.001) for 15:0 and 0.60 (P: < 0.001)
      for 15:0 + 17:0. Corresponding correlations with serum cholesterol esters were
      0.34 (P: < 0.001) (14:0), 0.45 (P: < 0.001) (15:0) and 0.56 (P: < 0.001) (15:0 +
      17:0), and with serum phospholipids the values were 0.30 (P: < 0.01) (14:0), 0.50
      (P: < 0.001) (15:0) and 0.50 (P: < 0.001) (15:0 plus 17:0). In our study
      population, the relative content of 15:0 or 14:0 in adipose tissue is a valid
      biomarker for long-term dairy fat intake in free-living individuals. When adipose
      tissue is not available, 15:0 content in serum cholesterol esters or
      phospholipids might be used. Intake data based on repeated 24-h recalls are
      equally informative and may be an equivalent choice in nutritional studies.

PMID- 11238767
TI  - More antioxidants in cocoa.

PMID- 11238770
TI  - Introduction. Symposium: Leucine as a nutritional signal.

PMID- 11238771
TI  - Regulation of branched-chain alpha-keto acid dehydrogenase kinase expression in
      rat liver.
AB  - Branched-chain amino acids are toxic in excess but have to be conserved for
      protein synthesis. This is accomplished in large part by control of the activity
      of the branched-chain alpha-keto acid dehydrogenase complex by
      phosphorylation/dephosphorylation. Regulation of the activity of the hepatic
      enzyme appears particularly important, at least in rats, since an exceptional
      high activity of the complex in this tissue makes the liver the primary clearing
      house for excess branched-chain alpha-keto acids released by other tissues. The
      degree to which the branched-chain alpha-keto acid dehydrogenase complex is
      inactivated by phosphorylation is determined by the activity of the branched
      chain alpha-keto acid dehydrogenase kinase, which is itself regulated by
      allosteric effectors as well as factors that affect its level of expression. Well
      established among these are the alpha-keto acid produced by leucine
      transamination, which is a potent inhibitor of the kinase, and starvation for
      dietary protein, which causes increased expression of the branched-chain alpha
      keto acid dehydrogenase kinase. The latter finding resulted in the working
      hypothesis that nutrients and hormones regulate expression of the branched-chain
      alpha-keto acid dehydrogenase kinase. Evidence has been obtained for the
      involvement of thyroid hormone, glucocorticoids and ligands for peroxisome
      proliferator-activated receptor alpha. Thyroid hormone induces, whereas
      glucocorticoids and peroxisome proliferator-activated receptor alpha ligands
      repress, expression of the kinase. Increased blood levels of thyroid hormone are
      proposed to be responsible for increased expression of branched-chain alpha-keto
      acid dehydrogenase kinase in animals starved for protein.

PMID- 11238772
TI  - Function of leucine in excitatory neurotransmitter metabolism in the central
      nervous system.
AB  - A novel hypothesis for the role of branched-chain amino acids (BCAA) in
      regulating levels of the major excitatory neurotransmitter glutamate in the
      central nervous system is described. It is postulated that the branched-chain
      aminotransferase (BCAT) isoenzymes (mitochondrial BCATm and cytosolic BCATc) are
      localized in different cell types and operate in series to provide nitrogen for
      optimal rates of de novo glutamate synthesis. BCAA enter the astrocyte where
      transamination is catalyzed by BCATm, producing glutamate and branched-chain
      alpha-keto acids (BCKA). BCKA, which are poorly oxidized in astrocytes, exit and
      are taken up by neurons. Neuronal BCATc catalyzes transamination of the BCKA with
      glutamate. The products, BCAA, exit the neuron and return to the astrocyte. The
      alpha-ketoglutarate product in the neurons may undergo reductive amination to
      glutamate via neuronal glutamate dehydrogenase. Operation of the shuttle in the
      proposed direction provides a mechanism for efficient nitrogen transfer between
      astrocytes and neurons and synthesis of glutamate from astrocyte alpha
      ketoglutarate. Evidence in favor of the hypothesis is: 1) The two BCAT isoenzymes
      appear to be localized separately in the neurons (BCATc) or in the astroglia
      (BCATm). 2) Inhibition of the shuttle in the direction of glutamate synthesis can
      be achieved by inhibiting BCATc using the neuroactive drug gabapentin. Although
      gabapentin does not inhibit BCATm, it does block de novo glutamate synthesis from
      alpha-ketoglutarate. 3) Conversely, gabapentin stimulates oxidation of glutamate.
      Inhibition of BCATc may allow BCKA to accumulate in the astroglia, thus
      facilitating conversion of glutamate to alpha-ketoglutarate.

PMID- 11238773
TI  - Molecular mechanisms in the brain involved in the anorexia of branched-chain
      amino acid deficiency.
AB  - The anterior piriform cortex (APC) of the rat is thought to be the site of
      indispensable amino acid (IAA) chemosensation in the brain. The branched-chain
      amino acids, including leucine, are among the IAA that are recognized in the APC.
      The behavioral outcome of IAA deficiency is an anorectic response. The specific
      transduction mechanisms by which IAA deficiency and repletion activate the APC
      are not fully understood, but clearly phosphorylation of proteins, increases in
      intracellular calcium, and expression of the immediate early gene c-fos, which
      are among the earliest events occurring after the initial drop in the
      concentration of the limiting IAA, cause stimulation in the APC. Subsequently,
      several neurotransmitter systems, including those for norepinephrine, GABA,
      serotonin, dopamine and nitric oxide, are activated in the APC of rats that have
      consumed an IAA-imbalanced diet. These systems appear to modulate the output
      cells from the APC, glutamatergic pyramidal cells that send neural signals to
      activate subsequent relays in the brain. Ultimately, the feeding circuits of the
      brain carry out the anorectic response. Continued consumption of a diet
      containing an IAA imbalance causes a conditioned taste aversion to the diet in
      all animals that have been studied. Such learning involves synaptic
      reorganization, requiring both degradation and synthesis of protein, along with
      alterations in genomic activity.

PMID- 11238774
TI  - Signaling pathways involved in translational control of protein synthesis in
      skeletal muscle by leucine.
AB  - Numerous reports established that in skeletal muscle the indispensable branched
      chain amino acid leucine is unique in its ability to initiate signal transduction
      pathways that modulate translation initiation. Oral administration of leucine
      stimulates protein synthesis in association with hyperphosphorylation of the
      translational repressor, eukaryotic initiation factor (eIF) 4E binding protein 1
      (4E-BP1), resulting in enhanced availability of the mRNA cap-binding protein
      eIF4E, for binding eIF4G and forming the active eIF4F complex. In addition,
      leucine enhances phosphorylation of the 70-kDa ribosomal protein S6 kinase
      (S6K1). These results suggest that leucine upregulates protein synthesis in
      skeletal muscle by enhancing both the activity and synthesis of proteins involved
      in mRNA translation. The stimulatory effects of leucine on translation initiation
      are mediated in part through the protein kinase mammalian target of rapamycin
      (mTOR), where both insulin signaling and leucine signaling converge to promote a
      maximal response.

PMID- 11238775
TI  - Role of leucine in the regulation of mTOR by amino acids: revelations from
      structure-activity studies.
AB  - In this study an overview is presented of the mTOR signaling pathway and its
      regulation by amino acids, particularly L-leucine. Our laboratory is studying
      amino acid regulation of mTOR in adipocytes. Potential roles for mTOR in
      adipocytes that were previously posited include hypertrophic growth, leptin
      secretion, protein synthesis and adipose tissue morphogenesis. A current area of
      interest in the field is how amino acids regulate mTOR and which amino acids are
      regulatory. Revelations concerning mechanism and recognition are emerging from
      different laboratories that examined the structural requirements for stimulation
      and inhibition of the mTOR signaling pathway by leucine and amino acid analogs.
      In adipocytes and some other cell types, leucine appears to be the main
      regulatory amino acid. However, this is not uniformly the case. In those cells
      where mTOR is regulated by several amino acids, there is evidence that the
      mechanism of mTOR activation may be different from cells where mainly leucine is
      regulatory. Furthermore, in tissues where leucine regulates mTOR, the possible
      existence of different tissue-specific leucine recognition sites may be
      indicated.

PMID- 11238776
TI  - Introduction. Symposium: Obesity in developing countries: biological and
      ecological factors.
AB  - Over the past decade there has been an increasing concern about the impact of
      chronic, noncommunicable diseases on the health of developing world populations.
      Traditionally, major causes of illness and death in developing countries have
      been linked to infectious diseases and undernutrition, and these are still major
      public health problems in several regions of the world. But recent projections
      indicate that in 20 y noncommunicable diseases will account for over 60% of the
      disease burden and mortality in the developing world. Obesity is recognized as an
      underlying risk factor for many of these chronic conditions. As in developed
      societies, the risk for obesity in developing countries is also strongly
      influenced by diet and lifestyle, which are changing dramatically as a result of
      the economic and nutrition transition. This symposium discusses key aspects of
      the phenomenon of obesity in the developing world and provides some specific
      examples from countries facing increasing prevalence of that condition.

PMID- 11238777
TI  - The nutrition transition and obesity in the developing world.
AB  - Changes in diet and activity patterns are fueling the obesity epidemic. These
      rapid changes in the levels and composition of dietary and activity/inactivity
      patterns in transitional societies are related to a number of socioeconomic and
      demographic changes. Using data mainly from large nationally representative and
      nationwide surveys, such as the 1989, 1991, 1993 and 1997 China Health and
      Nutrition Surveys, in combination with comparative analysis across the regions of
      the world, we examine these factors. First, we show the shifts in diet and
      activity are consistent with the rapid changes in child and adult obesity and in
      some cases have been causally linked. We then provide a few examples of the rapid
      changes in the structure of diet and activity, in particular associated with
      increased income. Cross-country and in-depth analysis of the China study are used
      to explore these relationships. People living in urban areas consume diets
      distinctly different from those of their rural counterparts. One of the more
      profound effects is the accelerated change in the structure of diet, only
      partially explained by economic factors. A second is the emergence of a large
      proportion of families with both currently malnourished and overweight members as
      is shown by comparative analysis of a number of Asian and Latin American
      countries.

PMID- 11238778
TI  - Early nutrition and later adiposity.
AB  - The objective was to review whether nutrition during pregnancy and the first 3 y
      of life predisposes individuals to be fatter as adults. The roles of
      undernutrition, overnutrition and breastfeeding were considered. The evidence
      that poor nutrition in early life is a risk factor for increased fatness later in
      life is inconclusive. Overnutrition, as proxied by high birthweight or
      gestational diabetes, on the other hand, is associated with subsequent fatness.
      Two large, well-conducted studies in developed countries suggest that
      breastfeeding has a protective effect. Nutrition in early life has a demonstrable
      but small impact on adult obesity.

PMID- 11238779
TI  - Independent effects of income and education on the risk of obesity in the
      Brazilian adult population.
AB  - With a view to assess the independent effects of income and education on the risk
      of obesity we studied cross-sectional randomly selected samples of the adult
      population (20 y and over) living in 1996/97 in the less (northeastern) and the
      more (southeastern) developed region of Brazil (1971 and 2588 northeastern and
      2289 and 2549 southeastern men and women, respectively). Independent effects of
      income and education on obesity (BMI > or = 30 kg/m(2)) were assessed through
      logistic regression analyses that controlled for age, ethnicity, household
      setting (urban or rural) and either education or income. The risk of obesity in
      men strongly increased with income in the two regions. The level of education did
      not influence the risk of male obesity in the less developed region but, in the
      more developed one, better-educated men had slightly less chance to be obese. In
      the less developed region obesity in women was strongly associated with both
      income (direct association) and education (inverse association). In the more
      developed region only the women's education influenced the risk of obesity, and
      the association between the two variables was inverse and strong as in the less
      developed region. Findings from this study reveal a scenario that is far from
      what has been generally admitted for the social distribution of obesity in the
      developing countries. They indicate that in transition societies income tends to
      be a risk factor for obesity, whereas education tends to be protective and that
      both gender and level of economic development are relevant modifiers of the
      influence exerted by these variables.

PMID- 11238780
TI  - Diet culture and obesity in northern Africa.
AB  - The etiology of obesity in North Africa is not well understood and few studies
      shed any light on its development among women. This study compiles what is known
      about the prevalence of obesity and its determinants in Morocco and Tunisia.
      Results from the authors' two surveys on nutrition-related disease among
      reproductive-age women (sample size: 2800) and their children (1200 children
      under 5 y and 500 adolescents) were combined with data from four national income
      and expenditure surveys (dating from 1980) to assess obesity trends and
      development in Morocco and Tunisia. Overall levels of obesity, identified by body
      mass index (BMI) > or = 30 kg/m(2), were 12.2% in Morocco and 14.4% in Tunisia.
      Obesity is significantly higher among women than among men in both countries
      (22.7% vs. 6.7% in Tunisia and 18% vs. 5.7% in Morocco) and prevalence among
      women has tripled over the past 20 y. Half of all women are overweight or obese
      (BMI > 25) with 50.9% in Tunisia and 51.3% in Morocco. Overweight increases with
      age and seems to take hold in adolescence, particularly among girls. In Tunisia,
      9.1% of adolescent girls are at risk for being overweight (BMI/age > or = 85th
      percentile). Prevalence of overweight and obesity are greater for women in urban
      areas and with lower education levels. Obese women in both countries take in
      significantly more calories and macronutrients than normal-weight women. The
      percentage contribution to calories from fat, protein and carbohydrates seems to
      be within normal limits, whereas fat intake is high (31%) in Tunisia and
      carbohydrate intake (65-67%) is high in Morocco. These are alarming trends for
      public health professionals and policy makers in countries still grappling with
      the public health effects of malnutrition and micronutrient deficiencies. Health
      institutions in these countries have an enormous challenge to change cultural
      norms that do not recognize obesity, to prevent significant damage to the
      public's health from obesity.

PMID- 11238781
TI  - Obesity trends in Latin America: transiting from under- to overweight.
AB  - Latin America is undergoing a rapid demographic and nutritional transition. A
      recent WHO/PAHO survey on obesity in the region revealed an increasing trend in
      obesity as countries emerge from poverty, especially in urban areas. In contrast,
      in middle income countries, obesity tends to decline as income increases; this is
      especially so in women. Dietary changes and increasing inactivity are considered
      the crucial contributory factors that explain this rise. The end result is a
      progressive rise in overweight and obesity, especially in low income groups who
      improve their income and buy high fat/high carbohydrate energy-dense foods.
      Intake of these foods increases to the detriment of grains, fruits and
      vegetables. Most aboriginal populations of the Americas have changed their diet
      and physical activity patterns to fit an industrialized country model. They now
      derive most of their diet from Western foods and live sedentary and physically
      inactive lives. Under these circumstances they develop high rates of obesity,
      insulin resistance and type 2 diabetes. Supplementary feeding programs are common
      in the region; the number of beneficiaries significantly exceeds the
      malnourished. Weight-for-age definition of undernutrition without assessment of
      length will overestimate the dimension of malnutrition and neglect the
      identification of stunted overweight children. Providing food to low income
      stunted populations may be beneficial for some, although it may be detrimental
      for others, inducing obesity especially in urban areas. Defining the right
      combination of foods/nutrients, education and lifestyle interventions that are
      required to optimize nutrition and health is a present imperative.

PMID- 11238782
TI  - Introduction. Symposium: Calorie restriction: effects on body composition,
      insulin signaling and aging.
AB  - At this time of increasing attention to the worldwide problem of obesity and its
      negative consequences for health and well being, it is timely to present a
      symposium on the effects of calorie restriction and the potential for calorie
      restriction mimetic therapies. The present symposium "Calorie Restriction:
      Effects on Body Composition, Insulin Signaling and Aging" was included in the
      Experimental Biology 2000 meeting held April 15-18, 2000 in San Diego,
      California. It is now recognized that calorie restriction carries with it many
      heretofore unrecognized consequences in addition to the life span-extending
      properties first described in the 1930s. This symposium addresses some of the
      current issues in calorie restriction and demonstrates the widespread effects
      that may underlie recidivism after weight loss, as well as the metabolically
      positive consequences for health of long-term calorie restraint.

PMID- 11238783
TI  - The role of fat depletion in the biological benefits of caloric restriction.
AB  - One of the most robust observations in the biology of aging is that caloric
      restriction (CR) extends life in a variety of species. Although CR results in
      substantial decrease in fat mass, the role of fat in life extension was
      considered minimal. Indeed, in the fields of obesity and diabetes, the amount of
      fat has been directly implicated in the metabolic consequences. Since it became
      apparent that fat is a massive endocrine tissue, some of its roles have been
      recently revised. Many of the systemic effects of CR can now be explained by the
      chronic effects related to decreased plasma levels of peptides, cytokines,
      complement factors and substrates that are produced in fat. Most of the benefits
      of CR on the neuroendocrine system and those related to the improvement in
      glucose homeostasis can be attributed to a decrease in adipose cells and their
      products. If all or most of the life-extending benefits of CR can be attributed
      to decreased fat stores, the expression of specific candidate substrates and
      proteins may be explored and manipulated in searching for the most powerful
      adipose-dependent signals that modulate life expectancy.

PMID- 11238784
TI  - In vivo insulin regulation of skeletal muscle glycogen synthase in calorie
      restricted and in ad libitum-fed rhesus monkeys.
AB  - Chronic calorie restriction in primates has been shown to have profound and
      unexpected effects on basal and on in vivo insulin action on skeletal muscle
      glycogen synthase (GS) activity. The decreased ability of insulin to activate
      skeletal muscle GS is a hallmark of insulin resistance and type 2 diabetes. The
      mechanism and role of in vivo insulin regulation of skeletal muscle GS are not
      fully understood. Two pathways for the activation of GS by insulin have been
      described by Larner and others: 1) insulin activates glucose transport that
      results in an increase in glucose-6-phosphate (G6P), thereby activating protein
      phosphatase-1, which in turn dephosphorylates and activates GS, therefore,
      pushing substrate into glycogen; and 2) insulin activates GS (perhaps by forming
      low-molecular-weight mediators which may activate protein phosphatase-1 and 2C)
      and activated GS subsequently pulls intermediates (e.g., G6P and uridine 5'
      diphosphoglucose) into glycogen. To determine whether in vivo insulin regulates
      glycogen synthesis primarily via a push or pull mechanism and how this mechanism
      might be affected by long-term calorie restriction, skeletal muscle samples were
      obtained before and during a euglycemic hyperinsulinemic clamp from 41 rhesus
      monkeys. The monkeys varied widely in their degree of insulin sensitivity and age
      and included chronically calorie-restricted (CR) monkeys and ad libitum-fed
      monkeys. The ad libitum-fed monkeys included spontaneously type 2 diabetic,
      prediabetic and clinically normal animals. The apparent affinity of GS for the
      allosteric activator G6P (G6P Ka of GS) was measured and compared with G6P
      content in the muscle samples. Basal G6P Ka of GS was lower in the CR monkeys
      compared with the 3 ad libitum-fed groups (P: < or = 0.05). Only the normal ad
      libitum-fed monkeys had a decrease in the G6P Ka of GS with insulin (P: < 0.005).
      The insulin effect (insulin-stimulated minus basal) on the G6P Ka of GS was
      strongly positively related to the insulin effect on G6P content (r = 0.80, P: <
      0.0001) across the entire group of monkeys. This finding supports the hypothesis
      that activation/dephosphorylation of GS by insulin is related to a decrease in
      G6P content and that paradoxical inactivation/phosphorylation of GS by insulin is
      related to an increase in G6P content (as demonstrated in 4 of 6 CR monkeys).
      Therefore, during a euglycemic hyperinsulinemic clamp, insulin regulates skeletal
      muscle glycogen synthesis primarily via a pull mechanism in both CR and in ad
      libitum-fed rhesus monkeys.

PMID- 11238785
TI  - Calorie restriction in obesity: prevention of kidney disease in rodents.
AB  - The incidence of end-stage renal disease (ESRD) has risen considerably in the
      past two decades. This trend is partly due to the alarming rise in the incidence
      of type 2 diabetes over the same period, which in turn might be linked to the
      staggering increase in overweight and obesity. If these trends continue, ESRD can
      be expected not only to cause suffering of ever growing numbers of patients, but
      also to become an increasing financial as well as logistical burden on the health
      care system. Therefore, it is imperative not only to gain a better understanding
      of the molecular, cellular and metabolic mechanisms involved in renal pathology,
      but also to uncover treatment modalities, including lifestyle changes, that can
      help prevent and/or slow the progression of kidney pathogenesis. Insights into
      both of these aspects are provided by animal models of obesity and diabetes. It
      has long been known that food restriction, more so than restriction of any
      particular dietary component, can greatly enhance longevity in laboratory
      rodents. These findings are being extended into a variety of other mammals,
      including nonhuman primates. These studies have indicated that caloric
      restriction in nonobese laboratory animals does not primarily affect specific
      disease processes but rather nonspecifically slows the aging process. In
      contrast, a growing body of evidence suggests that in genetically obese animals,
      food restriction can prevent or greatly delay the onset of specific degenerative
      lesions, in particular glomerulonephritis associated with obesity and diabetes.

PMID- 11238786
TI  - Microarray profiling of gene expression in aging and its alteration by caloric
      restriction in mice.
AB  - An active research area in biological gerontology concerns the mechanisms by
      which caloric restriction (CR) retards the aging process in laboratory rodents.
      We used high density oligonucleotide arrays representing 6347 genes to determine
      the gene expression profile of the aging process in gastrocnemius muscle of male
      C57BL/6 mice. Aging resulted in a differential gene expression pattern indicative
      of a marked stress response and lower expression of metabolic and biosynthetic
      genes. Most alterations were completely or partially prevented by CR.
      Transcriptional patterns of muscle from calorie-restricted animals suggest that
      CR retards the aging process by causing a metabolic shift toward increased
      protein turnover and decreased macromolecular damage. The use of high density
      oligonucleotide microarrays provides a new tool to measure biological age on a
      tissue-specific basis and to evaluate at the molecular level the efficacy of
      nutritional interventions designed to retard the aging process.

PMID- 11238787
TI  - Characterization of diet-dependent metabolic serotypes: analytical and biological
      variability issues in rats.
AB  - This report, the first in a series on diet-dependent changes in the serum
      metabolome (metabolic serotype), describes validation of the use of high
      performance liquid chromatography (HPLC) separations coupled with Coulometric
      array detectors to characterize changes in the metabolome. The long-term aim of
      these studies is to improve understanding of the effects of significant variation
      in nutritive status on physiology and on disease processes. Initial studies focus
      on identifying the effects of dietary (or caloric) restriction on the redox
      active components of rat serum. Identification of compounds of interest is being
      carried out using HPLC separations coupled with coulometric array analysis, an
      approach allowing simultaneous examination of nearly 1200 serum compounds. The
      technical and practical issues discussed in this report are related to both
      analytical validity (HPLC running conditions, computer-automated peak
      identification, mathematical compensation for chromatographic drift, etc.) and
      biological variability (individual variability, cohort-cohort variability,
      outliers). Attention to these issues suggests approximately 250 compounds in
      serum are sufficiently reliable, both analytically and biologically, for
      potential use in building mathematical models of serotype.

PMID- 11238788
TI  - Introduction. Symposium: Pediatric pulmonary insufficiency: nutritional
      strategies for prevention and treatment.

PMID- 11238789
TI  - Energy expenditure in infants with pulmonary insufficiency: is there evidence for
      increased energy needs?
AB  - The observed growth failure in infants with pulmonary insufficiency is postulated
      to be a consequence of elevated rates of energy expenditure. Assessment of energy
      expenditure by the classical technique of indirect calorimetry has yielded
      conflicting results. The adoption of the newer, doubly labeled water technique
      has provided evidence to support increased rates of energy expenditure in infants
      with chronic lung disease, congenital heart disease and in minimally ill,
      extremely low birth weight infants. The doubly labeled water technique holds
      great promise for the detailed study of energy expenditure in a variety of
      clinical conditions, including very ill as well as free-living subjects.

PMID- 11238790
TI  - Chronic pulmonary insufficiency in children and its effects on growth and
      development.
AB  - Conditions leading to chronic pulmonary insufficiency can affect infants and
      children. These can lead to growth failure and delayed development. Among the
      most common and severe of these are bronchopulmonary dysplasia (BPD) and cystic
      fibrosis. In addition to the respiratory consequences of these diseases, there is
      ample evidence that they lead to decreased growth as a result of decreased energy
      intake and increased energy expenditure. Furthermore, there is evidence that
      infants with BPD may also have delayed development, independent of the effects of
      their prematurity. Enhancing the long-term outlook for these conditions may
      therefore require consideration of both improved pulmonary management and
      aggressive nutritional management to limit growth failure and potentially enhance
      developmental outcome. Specific micronutrient supplementation, such as
      antioxidant therapy, may also enhance pulmonary and nutritional status.

PMID- 11238791
TI  - Special nutritional needs of infants for prevention of and recovery from
      bronchopulmonary dysplasia.
AB  - Extremely low birth weight infants who develop severe respiratory disease may
      have special nutrient requirements imposed by a combination of enhanced
      utilization of nutrients or the need for epithelial cell repair resulting from
      the disease process, as well as to support catch-up growth. Inositol, free fatty
      acids, vitamin E and vitamin A are proposed as nutrients for which infants at
      risk of chronic pulmonary insufficiency may have special requirements. Of these
      nutrients, only for vitamin A does suggestive evidence exist that high doses when
      given intramuscularly may reduce the incidence of death or chronic lung disease.
      Exogenous steroid therapy (dexamethasone), which is often used to improve
      pulmonary compliance in ventilated premature infants, may compromise vitamin A
      status and induce restricted somatic and bone mineral growth. Supplemental
      nutrition by means of enriched infant formulas has provided benefits in growth
      and bone mass accretion to infants recovering from bronchopulmonary dysplasia up
      to 3-mo corrected age. This growth advantage was not sustained over the
      subsequent 9 mo, suggesting that prolonged nutritional support is required until
      catch-up growth is complete. Further studies are required to delineate the needs
      for specific nutrients such as antioxidant vitamins and minerals or vitamin A
      that may play a role in preventing severe chronic lung disease in premature
      infants. As well, the role of supplemental nutrition (beyond the requirements of
      term infants) to support catch-up growth and maintenance during the critical
      stages of early development requires further investigation before evidence-based
      nutrient recommendations can be developed for this special population of infants.

PMID- 11238792
TI  - Is there a role for antioxidant therapy in bronchopulmonary dysplasia?
AB  - Bronchopulmonary dysplasia (BPD) is a chronic lung disease first described in
      1967 as a complication of therapy for premature infants with hyaline membrane
      disease, and treatment with high concentrations of oxygen was thought to be a
      major contributor to its development. Thus, interventions to enhance lung
      antioxidants to prevent the development of BPD were considered appropriate
      therapeutic strategies. In the last decades, advances in the acute care of
      premature infants has reduced the reliance on therapy with high concentrations of
      supplemental oxygen. However, the incidence of BPD has not changed significantly.
      The changing clinical context in which BPD develops begs the question of whether
      oxidation is important in the development of BPD and, therefore, whether
      designing interventions enhancing lung antioxidants is still warranted. This
      review presents evidence that premature infants that will develop BPD have
      qualitative and quantitative differences in oxidation of lipids and proteins when
      compared to infants that do not develop BPD. Such differences in oxidation
      patterns are the most obvious in the first few days of life. The emerging
      evidence thus supports the concept that the lung injury process leading to the
      development of BPD occurs within hours to days of delivery and that oxidation is
      a major contributor to this pathological process. Unfortunately, early attempts
      at delivery of antioxidants to the lung have not been successful, perhaps because
      of an inability to deliver antioxidants in a timely manner to the areas in the
      lung in which deleterious oxidations are occurring. Further research is necessary
      to determine both the nature and the location of the oxidative events that lead
      to the development of early lung injury, so that more appropriate and specific
      antioxidant interventions can be designed.

PMID- 11238795
TI  - Historical perspective on the use of garlic.
AB  - The objective of this review is to examine briefly the medical uses of garlic
      throughout the ages and the role that it was considered to play in prevention and
      treatment of disease. Interest in the potential benefits of garlic has origins in
      antiquity and is one of the earliest documented examples of plants employed for
      treatment of disease and maintenance of health. Garlic was in use at the
      beginning of recorded history and was found in Egyptian pyramids and ancient
      Greek temples. There are Biblical references to garlic. Ancient medical texts
      from Egypt, Greece, Rome, China and India each prescribed medical applications
      for garlic. In many cultures, garlic was administered to provide strength and
      increase work capacity for laborers. Hippocrates, the revered physician,
      prescribed garlic for a variety of conditions. Garlic was given to the original
      Olympic athletes in Greece, as perhaps one of the earliest "performance
      enhancing" agents. It is of interest that cultures that developed without contact
      with one another came to similar conclusions about the efficacy of garlic. Modern
      science is tending to confirm many of the beliefs of ancient cultures regarding
      garlic, defining mechanisms of action and exploring garlic's potential for
      disease prevention and treatment.

PMID- 11238796
TI  - Intake of garlic and its bioactive components.
AB  - The health benefits of garlic likely arise from a wide variety of components,
      possibly working synergistically. The complex chemistry of garlic makes it
      plausible that variations in processing can yield quite different preparations.
      Highly unstable thiosulfinates, such as allicin, disappear during processing and
      are quickly transformed into a variety of organosulfur components. The efficacy
      and safety of these preparations in preparing dietary supplements based on garlic
      are also contingent on the processing methods employed. Although there are many
      garlic supplements commercially available, they fall into one of four categories,
      i.e., dehydrated garlic powder, garlic oil, garlic oil macerate and aged garlic
      extract (AGE). Garlic and garlic supplements are consumed in many cultures for
      their hypolipidemic, antiplatelet and procirculatory effects. In addition to
      these proclaimed beneficial effects, some garlic preparations also appear to
      possess hepatoprotective, immune-enhancing, anticancer and chemopreventive
      activities. Some preparations appear to be antioxidative, whereas others may
      stimulate oxidation. These additional biological effects attributed to AGE may be
      due to compounds, such as S-allylcysteine, S-allylmercaptocysteine, N(alpha)
      fructosyl arginine and others, formed during the extraction process. Although not
      all of the active ingredients are known, ample research suggests that several
      bioavailable components likely contribute to the observed beneficial effects of
      garlic.

PMID- 11238797
TI  - How to distinguish garlic from the other Allium vegetables.
AB  - The establishment of international monographs for herbs is in progress. Here, we
      propose both a marker compound and a method for its analysis for the
      identification of garlic bulbs and their products. The constituents in 26 kinds
      of fresh edible parts of Allium vegetables and three types of garlic preparations
      were analyzed. Sulfur compounds are the most characteristic constituents in
      garlic, but manufacturing processes of garlic products dramatically affect these
      constituents. Thus, no sulfur compound could be specified as a universal marker
      of identification applicable for any type of garlic. On the other hand, garlic
      contains other characteristic compounds, namely, saponins. After analyzing Allium
      vegetables and garlic preparations, we concluded that sapogenins, especially beta
      chlorogenin, may be a viable candidate for identifying and distinguishing garlic
      from other Allium vegetables.

PMID- 11238798
TI  - Determination of allicin, S-allylcysteine and volatile metabolites of garlic in
      breath, plasma or simulated gastric fluids.
AB  - Various components of garlic and aged garlic extract, including allicin, S
      allylcysteine (SAC) and volatile metabolites of allicin were determined in
      breath, plasma and simulated gastric fluids by HPLC, gas chromatography (GC) or
      HPLC- and GC-mass spectrometry (MS). Data indicate that allicin decomposes in
      stomach acid to release allyl sulfides, disulfides and other volatiles that are
      postulated to be metabolized by glutathione and/or S-adenosylmethionine to form
      allyl methyl sulfide. SAC can be absorbed by the body and can be determined in
      plasma by HPLC or HPLC-MS using atmospheric pressure chemical ionization (APCI)
      MS.

PMID- 11238799
TI  - N alpha-(1-deoxy-D-fructos-1-yl)-L-arginine, an antioxidant compound identified
      in aged garlic extract.
AB  - Aged garlic extract (AGE) has been shown to have antioxidant activity. The
      organosulfur compounds, S-allyl-L-cysteine and S-allylmercapto-L-cysteine, are
      responsible, at least in part, for the antioxidant activity of AGE. To identify
      major active components, we fractionated AGE, using hydrogen peroxide scavenging
      activity as an antioxidative index. Strong activity in the amino acid fraction
      was found and the major active compound was identified as N alpha-(1-deoxy-D
      fructos-1-yl)-L-arginine (Fru-Arg). Antioxidant activity of Fru-Arg was
      comparable to that of ascorbic acid, scavenging hydrogen peroxide completely at
      50 micromol/L and 37% at 10 micromol/L. Quantitative analysis using the
      established HPLC system revealed that AGE contained 2.1-2.4 mmol/L of Fru-Arg,
      but none was detected in either raw or heated garlic juice. Furthermore, it was
      shown that a minimum of 4 mo aging incubation was required for Fru-Arg to be
      generated. These findings indicate that the aging process is critical for the
      production of the antioxidant compound, Fru-Arg. These results may explain some
      of the variation in benefits among different commercially available garlic
      preparations.

PMID- 11238800
TI  - Historical perspective on garlic and cardiovascular disease.
AB  - Cardiovascular disease is a complex and multifactorial disease characterized by
      such factors as high cholesterol, hypertension, reduced fibrinolysis, increase in
      blood-clotting time and increased platelet aggregation. Dietary therapy is the
      first step in the treatment of hyperlipidemia; garlic has been used medicinally
      for centuries and is still included in the traditional medicine of many cultures.
      Historically, there has been great interest in the role of garlic in reducing
      cardiovascular risk factors. Evidence from numerous studies points to the fact
      that garlic can bring about the normalization of plasma lipids, enhancement of
      fibrinolytic activity, inhibition of platelet aggregation and reduction of blood
      pressure and glucose. However, some contradictory results have also emerged as a
      result of methodological shortcomings, the use of different
      formulations/preparations of garlic and different time scales of the studies.
      Accordingly, further clinical studies are required in which standardized
      formulations of garlic with known compositions can be used. Such formulations
      (e.g., Aged Garlic Extract) are now available and are being investigated.
      Evidence obtained from these studies indicates that garlic has potential in the
      prevention and control of cardiovascular disorders and is beneficial when taken
      as a dietary supplement.

PMID- 11238801
TI  - Aged garlic extract, a modulator of cardiovascular risk factors: a dose-finding
      study on the effects of AGE on platelet functions.
AB  - Aged garlic extract (AGE) has been shown previously to have moderate cholesterol
      lowering and blood pressure-reducing effects. We have now investigated whether
      platelet function, a potential risk factor for cardiovascular disease, can be
      inhibited by AGE administration. In a randomized, double-blind study of normal
      healthy individuals (n = 34), both men and women, the effect of AGE was evaluated
      in doses between 2.4 and 7.2 g/d vs. equal amounts of placebo. Platelet
      aggregation and adhesion were measured at 2-wk intervals throughout the study.
      Threshold concentrations for epinephrine and collagen increased moderately during
      AGE administration compared with the placebo and baseline periods. Only at the
      highest supplementation level did AGE show a slight increase in the threshold
      level of ADP-induced aggregation. Platelet adhesion to collagen, fibrinogen and
      von Willebrand factor was investigated by perfusing whole blood through a laminar
      flow chamber under controlled flow conditions. Adherence of platelets was
      inhibited by AGE in a dose-dependent manner when collagen was the adhesive
      surface perfused at low shear rates ( approximately 30 s(-1)). At high shear
      rates (1200 s(-1)), AGE also inhibited platelet adhesion to collagen but only at
      higher intake levels. Adhesion to von Willebrand factor was reduced only at 7.2
      g/d AGE, but adherence to fibrinogen was potently inhibited at all levels of
      supplementation. Thus, AGE exerts selective inhibition on platelet aggregation
      and adhesion, platelet functions that may be important for the development of
      cardiovascular events such as myocardial infarction and ischemic stroke. We
      briefly review the effect of garlic preparations in general on cardiovascular
      risk factors and point out differences between AGE and other garlic preparations
      that we feel are important to explain the efficacy of AGE.

PMID- 11238802
TI  - Suppression of LDL oxidation by garlic.
AB  - It has been known for several decades that hypercholesterolemia is a major risk
      factor for atherosclerosis and that lowering of cholesterol can significantly
      reduce risk for cardiovascular diseases. More recently, oxidation of LDL has been
      recognized as playing an important role in the initiation and progression of
      atherosclerosis. Oxidized LDL, but not native LDL, promotes vascular dysfunction
      by exerting direct cytotoxicity toward endothelial cells, by increasing
      chemotactic properties for monocytes, by transforming macrophages to foam cells
      via scavenger-receptors and by enhancing the proliferation of various cell types,
      e.g., endothelial cells, monocytes and smooth muscle cells; all of these events
      are recognized as contributing to atherogenesis. In this paper, experimental
      evidence is presented that shows that several garlic compounds can effectively
      suppress LDL oxidation in vitro. Short-term supplementation of garlic in human
      subjects has demonstrated an increased resistance of LDL to oxidation. These data
      suggest that suppressed LDL oxidation may be one of the powerful mechanisms
      accounting for the antiatherosclerotic properties of garlic.

PMID- 11238803
TI  - Cholesterol-lowering effect of garlic extracts and organosulfur compounds: human
      and animal studies.
AB  - The medicinal use of garlic dates back thousands of years, but there was little
      scientific support of its therapeutic and pharmacologic properties until
      recently. In the past decade, the cancer-protective effects of garlic have been
      well established by epidemiologic studies and animal experiments. However, the
      cardiovascular-protective properties of garlic are less well understood. In
      particular, despite the reported hypocholesterolemic effect of garlic, the
      mechanism of the effect is unclear. In a recent randomized, double-blind, placebo
      controlled intervention study, we showed that aged garlic extract (AGE)
      supplementation was effective in lowering plasma concentration of total
      cholesterol by 7% and LDL cholesterol by 10% in hypercholesterolemic men compared
      with subjects consuming a placebo. Supplementation of AGE in animal diets
      similarly reduced plasma concentrations of total cholesterol and triacylglycerol
      by 15 and 30%, respectively. In subsequent experiments using cultured rat
      hepatocytes, we found 44--87% inhibition of cholesterol synthesis by the water
      extractable fraction (WEF), methanol-extractable fraction (MEF) and petroleum
      ether-extractable fraction (PEF) of fresh garlic, and Kyolic (liquid form of
      AGE). These observations suggested that hydrophilic and hydrophobic compounds of
      garlic are inhibitory to cholesterol synthesis. Because S-allylcysteine (SAC)
      alone was less potent than Kyolic, which contains SAC and other sulfur compounds,
      a maximal inhibition appears to require a concerted action of multiple compounds
      of garlic. In a series of experiments, we further characterized the inhibitory
      potency of individual water-soluble and lipid-soluble compounds of garlic. Among
      water-soluble compounds, SAC, S-ethylcysteine (SEC), and S-propylcysteine (SPC)
      inhibited cholesterol synthesis by 40--60% compared with 20--35% by gamma
      glutamyl-S-allylcysteine (GSAC), gamma-glutamyl-S-methylcysteine (GSMC) and gamma
      glutamyl-S-propylcysteine (GSPC). Lipid-soluble sulfur compounds (i.e., diallyl
      sulfide, diallyl disulfide, diallyl trisulfide, dipropyl sulfide and dipropyl
      trisulfide) at low concentrations (0.05--0.5 mol/L) slightly (10--15%) inhibited
      cholesterol synthesis but became highly cytotoxic at high concentrations (1.0-
      4.0 mol/L). All water-soluble compounds, except S-allylmercaptocysteine, were not
      cytotoxic, judging from the release of cellular lactate dehydrogenase into the
      culture medium. Taken together, the results of our studies indicate that the
      cholesterol-lowering effects of garlic extract, such as AGE, stem in part from
      inhibition of hepatic cholesterol synthesis by water-soluble sulfur compounds,
      especially SAC.

PMID- 11238804
TI  - Study of garlic extracts and fractions on cholesterol plasma levels and vascular
      reactivity in cholesterol-fed rats.
AB  - Garlic is known for its pharmacologic and nutritional properties. In previous
      studies, garlic elicited a reduction in plasma levels of lipids by inhibiting
      hepatic cholesterol synthesis. The aim of this study was to investigate in an in
      vivo model the effects of garlic extract and some fractions on cholesterol levels
      and vascular reactivity in cholesterol-fed rats. Rats were fed a cholesterol
      enriched diet for 16 wk and were divided into 10 groups as follows: control and
      hypercholesterolemic diet groups, 4 groups fed frozen garlic fractions and 4
      groups fed raw garlic fractions with different doses. Blood samples were obtained
      to analyze HDL and LDL cholesterol levels. After treatment, rats were killed. The
      heart, liver and kidneys were weighed; the aorta was isolated, mounted in organ
      chambers and vascular reactivity was tested. Plasma concentration of cholesterol
      was 58 mg/dL (100%) at the beginning of the study and increased to 102 mg/dL
      (153%; hypercholesterolemic group) at the end of the treatment. Plasma total
      cholesterol decreased in all groups treated with garlic; moreover, this effect
      was higher in rats fed raw garlic fractions and extracts. LDL decreased
      significantly with respect to the hypercholesterolemic group in all groups
      treated with garlic fractions and extracts (P: < 0.01); however, an increase in
      HDL was found in those treated with frozen fractions and extracts. The liver:body
      weight ratio decreased in all treated groups. The relaxing effect of
      acetylcholine (ACh) was enhanced in arteries contracted with noradrenaline (NE).
      These data suggest that garlic fractions could prevent diet-induced
      hypercholesterolemia and vascular alterations in the endothelium-dependent
      relaxation associated with atherosclerosis.

PMID- 11238805
TI  - Saponins in garlic as modifiers of the risk of cardiovascular disease.
AB  - Most chemical and biological studies about garlic have been conducted using
      organosulfur compounds. However, a variety of steroid saponins from garlic and
      related Allium species are being increasingly recognized for their importance in
      biological processes. This report demonstrates the isolation and structure
      determination of steroid saponins from garlic and aged garlic extract (AGE). In
      addition, the in vitro antifungal antitumor cytotoxicity and blood coagulability
      effects of steroid saponins from garlic and related Allium species are provided.
      Animal studies on the cholesterol-lowering effects of the saponin fractions from
      garlic are also summarized.

PMID- 11238806
TI  - Molecular basis by which garlic suppresses atherosclerosis.
AB  - The aim of this study was to determine the mechanism by which the aged garlic
      extract "Kyolic" has a protective effect against atherosclerosis. Plasma
      cholesterol of rabbits fed a 1% cholesterol-enriched diet for 6 wk was not
      reduced by supplementation with 800 microL Kyolic/(kg body. d). In spite of this,
      Kyolic reduced by 64% (P < 0.05) the surface area of the thoracic aorta covered
      by fatty streaks and significantly reduced aortic arch cholesterol. Kyolic also
      significantly inhibited by approximately 50% the development of thickened, lipid
      filled lesions in preformed neointimas produced by Fogarty 2F balloon catheter
      injury of the right carotid artery in cholesterol-fed rabbits. In vitro studies
      found that Kyolic completely prevented vascular smooth muscle phenotypic change
      from the contractile, high volume fraction of filament (V(v)myo) state, and
      inhibited proliferation of smooth muscle cells in the synthetic state with a 50%
      effective dose (ED(50)) of 0.2%. Kyolic also slightly inhibited the accumulation
      of lipid in cultured macrophages but not smooth muscle, and had no effect on the
      expression of adhesion molecules on the surface of the endothelium or the
      adherence of leukocytes. It is concluded that Kyolic exerts antiatherogenic
      effects through inhibition of smooth muscle phenotypic change and proliferation,
      and by another (unclarified) effect on lipid accumulation in the artery wall.

PMID- 11238807
TI  - Antioxidant health effects of aged garlic extract.
AB  - Oxidative modification of DNA, proteins and lipids by reactive oxygen species
      (ROS) plays a role in aging and disease, including cardiovascular,
      neurodegenerative and inflammatory diseases and cancer. Extracts of fresh garlic
      that are aged over a prolonged period to produce aged garlic extract (AGE)
      contain antioxidant phytochemicals that prevent oxidant damage. These include
      unique water-soluble organosulfur compounds, lipid-soluble organosulfur
      components and flavonoids, notably allixin and selenium. Long-term extraction of
      garlic (up to 20 mo) ages the extract, creating antioxidant properties by
      modifying unstable molecules with antioxidant activity, such as allicin, and
      increasing stable and highly bioavailable water-soluble organosulfur compounds,
      such as S-allylcysteine and S-allylmercaptocysteine. AGE exerts antioxidant
      action by scavenging ROS, enhancing the cellular antioxidant enzymes superoxide
      dismutase, catalase and glutathione peroxidase, and increasing glutathione in the
      cells. AGE inhibits lipid peroxidation, reducing ischemic/reperfusion damage and
      inhibiting oxidative modification of LDL, thus protecting endothelial cells from
      the injury by the oxidized molecules, which contributes to atherosclerosis. AGE
      inhibits the activation of the oxidant-induced transcription factor, nuclear
      factor (NF)-kappa B, which has clinical significance in human immunodeficiency
      virus gene expression and atherogenesis. AGE protects DNA against free radical-
      mediated damage and mutations, inhibits multistep carcinogenesis and defends
      against ionizing radiation and UV-induced damage, including protection against
      some forms of UV-induced immunosuppression. AGE may have a role in protecting
      against loss of brain function in aging and possess other antiaging effects, as
      suggested by its ability to increase cognitive functions, memory and longevity in
      a senescence-accelerated mouse model. AGE has been shown to protect against the
      cardiotoxic effects of doxorubicin, an antineoplastic agent used in cancer
      therapy and against liver toxicity caused by carbon tetrachloride (an industrial
      chemical) and acetaminophen, an analgesic. Substantial experimental evidence
      shows the ability of AGE to protect against oxidant-induced disease, acute damage
      from aging, radiation and chemical exposure, and long-term toxic damage. Although
      additional observations are warranted in humans, compelling evidence supports the
      beneficial health effects attributed to AGE, i.e., reducing the risk of
      cardiovascular disease, stroke, cancer and aging, including the oxidant-mediated
      brain cell damage that is implicated in Alzheimer's disease.

PMID- 11238808
TI  - The effects of aged garlic extract on lipid peroxidation and the deformability of
      erythrocytes.
AB  - The effects of aged garlic extract (AGE) on lipid peroxidative damage and the
      deformability of erythrocytes were evaluated in rats. The deformability of
      erythrocytes was measured using the micropore filtration method. AGE
      significantly prevented the decrease of erythrocyte deformability induced by
      lipid peroxidation in a dose-dependent manner. The addition of AGE significantly
      inhibited an increase in thiobarbituric acid-reactive substances (TBARS) and
      hemolysis rate and prevented the loss of intraerythrocytic ATP and 2,3
      diphosphoglycerate (2,3-DPG) in oxidized erythrocytes. Moreover, AGE
      significantly suppressed not only the hemolysis rate induced by peroxidation but
      also hemolysis due to nonperoxidation. These results suggest the possibility that
      AGE improves microcirculation and rheological blood properties and preserves the
      structure and function of erythrocytes not only through an antioxidant process,
      but also via the glycolysis pathway and membrane stabilization of erythrocytes.

PMID- 11238809
TI  - Garlic compounds minimize intracellular oxidative stress and inhibit nuclear
      factor-kappa b activation.
AB  - Oxidative modification of LDL has been recognized as playing an important role in
      the initiation and progression of atherosclerosis. In this study, we determined
      the effects of aged garlic extract (AGE) and its major compound, S-allylcysteine
      (SAC), on oxidized LDL (Ox-LDL)-induced injury in endothelial cells (EC). Lactate
      dehydrogenase (LDH) release as an index of membrane damage, methylthiazol
      tetrazoium (MTT) assay for cell viability and thiobarbituric acid reactive
      substances (TBARS) indicating lipid peroxidation were measured. Ox-LDL caused an
      increase of LDH release, loss of cell viability and TBARS formation. Both AGE and
      SAC prevented all of these changes. To elucidate the mechanism, effects of AGE or
      SAC on intracellular glutathione (GSH) level in EC, and release of peroxide from
      EC and macrophages (M Phi) were determined. Ox-LDL depleted intracellular GSH and
      increased release of peroxides. Both AGE and SAC inhibited these changes. Effects
      of SAC on hydrogen peroxide (H(2)O(2)) or tumor necrosis factor (TNF)-alpha
      induced nuclear factor (NF)-kappa B activation were determined. Pretreatment of
      EC with SAC inhibited NF-kappa B activation. We demonstrated that both AGE and
      SAC can protect EC from Ox-LDL-induced injury by preventing intracellular GSH
      depletion in EC and by minimizing release of peroxides from EC and M Phi. SAC
      also inhibited H(2)O(2)- or TNF-alpha-induced NF-kappa B activation. Our data
      suggest that AGE and its main compound, SAC, may be useful for prevention of
      atherosclerosis.

PMID- 11238810
TI  - A historical perspective on garlic and cancer.
AB  - Epidemiological and laboratory studies provide insight into the anticarcinogenic
      potential of garlic and its constituent compounds. Both water- and lipid-soluble
      allyl sulfur compounds are effective in blocking a myriad of chemically induced
      tumors. Part of the protection from these compounds probably relates to a block
      in nitrosamine formation and metabolism. However, blockage in the initiation and
      promotion phases of the carcinogenicity of various compounds, including
      polycyclic hydrocarbons, provide evidence that garlic and its constituents can
      alter several phase I and II enzymes. Their ability to block experimentally
      induced tumors in a variety of sites including skin, mammary and colon, suggests
      a general mechanism of action. Changes in DNA repair and in immunocompetence may
      also account for some of this protection. Some, but not all, allyl sulfur
      compounds can also effectively retard tumor proliferation and induce apoptosis.
      Changes in cellular thiol and phosphorylation stains may account for some of
      these antitumorigenic properties. The anticarcinogenic potential of garlic can be
      influenced by several dietary components including specific fatty acids,
      selenium, and vitamin A. Since garlic and its constituents can suppress
      carcinogen formation, carcinogen bioactivation, and tumor proliferation it is
      imperative that biomarkers be established to identify which individuals might
      benefit most and what intakes can occur with ill consequences.

PMID- 11238811
TI  - Garlic and cancer: a critical review of the epidemiologic literature.
AB  - Animal and in vitro studies provide evidence of an anticarcinogenic effect of
      active ingredients in garlic. This review of the epidemiologic literature on
      garlic consumption addresses cancers of the stomach, colon, head and neck, lung,
      breast and prostate. Nineteen studies reported relative risk estimates for garlic
      consumption and cancer incidence. Site-specific case-control studies of stomach
      and colorectal cancer, in which multiple reports were available, suggest a
      protective effect of high intake of raw and/or cooked garlic. Cohort studies
      confirm this inverse association for colorectal cancer. Few cohort and case
      control studies for other sites of cancer exist. Garlic supplements, as analyzed
      in four cohort studies and one case-control report, from two distinct
      populations, do not appear to be related to risk. Low study power, lack of
      variability in garlic consumption categorization within studies and poor
      adjustment for potential cofounders may limit the reliability of any conclusions
      regarding garlic supplements. However, an indication of publication bias was also
      found by visual inspection of a funnel plot and in a log-rank test (P = 0.004).
      Evidence from available studies nevertheless suggests a preventive effect of
      garlic consumption in stomach and colorectal cancers. The study limitations
      indicate the need for more definitive research and improved nutritional
      epidemiologic analyses of dietary data.

PMID- 11238813
TI  - Impact of garlic organosulfides on p21(H-ras) processing.
AB  - This study describes the novel anticarcinogenic activity of diallyl disulfide, a
      naturally occurring organosulfide from garlic. Oral administration of diallyl
      disulfide resulted in a dose-dependent and significant inhibition of the growth
      of H-ras oncogene transformed NIH 3T3 cells implanted in nude mice. The effect of
      diallyl disulfide was apparent in terms of delay in the appearance of measurable
      tumors, tumor volume and tumor weight. On the other hand, the growth of H-ras
      oncogene transformed tumors was not inhibited by dipropyl disulfide, a naturally
      occurring saturated analog of diallyl disulfide. The diallyl disulfide-mediated
      inhibition of H-ras oncogene transformed tumor growth correlated with the
      inhibition of p21(H-ras) membrane association. The levels of membrane-associated
      p21(H-ras) were markedly lower in the tumors of diallyl disulfide-treated mice
      than in those of controls. An opposite trend, however, was evident for the
      cytosolic p21(H-ras). The results of this study indicate that diallyl disulfide
      inhibits the growth of H-ras oncogene transformed tumors in vivo by inhibiting
      the membrane association of p21(H-ras) and that the allyl group may be an
      important determinant in the inhibitory effect of this organosulfide on tumor
      growth.

PMID- 11238812
TI  - Mechanisms of inhibition of chemical toxicity and carcinogenesis by diallyl
      sulfide (DAS) and related compounds from garlic.
AB  - Diallyl sulfide (DAS) is a flavor compound derived from garlic and is
      sequentially converted to diallyl sulfoxide (DASO) and diallyl sulfone (DASO(2))
      by cytochrome P(450) 2E1 (CYP2E1). These compounds have been shown to reduce the
      incidence of a multitude of chemically induced tumors in animal models. The
      impediment of phase I activation of these carcinogens is hypothesized to be
      accountable for the reduction in tumor incidence. Indeed, DAS, DASO and DASO(2)
      are competitive inhibitors of CYP2E1. DASO(2), in addition, is a suicide
      inhibitor of CYP2E1. These compounds have been shown to reduce carbon
      tetrachloride-, N-nitrosodimethylamine- and acetaminophen-induced toxicity in
      rodents. All three chemicals are substrates for CYP2E1. The protective effect was
      observed when the organosulfur compounds were given before, during or soon after
      chemical treatment. DAS and DASO(2) inhibited the bioactivation of 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and related lung tumorigenesis
      in A/J mice. Because CYP2E1 does not play a key role in NNK activation, the
      inhibition of other CYP enzymes active in NNK metabolism is likely. DAS also has
      been shown to induce other CYP and phase II enzymes as well as decrease hepatic
      catalase activity. All of these effects are observed at concentrations much
      higher than what is normally ingested by humans. The biological activities of
      garlic and its related compounds at lower concentrations that mimic human
      consumption remain to be studied further.

PMID- 11238814
TI  - Suppression of chemical carcinogenesis by water-soluble organosulfur compounds.
AB  - The chemopreventive effects of five water-soluble organosulfur compounds, S
      methylcysteine (SMC) and four analogs, were examined on the promotion stage of
      diethylnitrosamine hepatocarcinogenesis in male F344 rats, using the medium-term
      bioassay (Ito test), which is based on the two-step model of
      hepatocarcinogenesis. In addition, we investigated the modifying effects of SMC
      and cysteine on the initiation stage of rat hepatocarcinogenesis. Carcinogenic
      potential was scored by comparing the numbers and areas of a putative neoplastic
      lesion, glutathione S-transferase placental form (GST-P)--positive hepatocellular
      foci. SMC and cysteine significantly decreased the number and area of GST-P-
      positive foci when given in the promotion stage of the Ito test. When given
      during the initiation stage, these two organosulfur compounds also significantly
      inhibited focus formation. Liver ornithine decarboxylase activity after two
      thirds partial hepatectomy and the proportion of hepatocytes positive for
      proliferating cell nuclear antigen significantly decreased the number of aberrant
      crypt foci in the colon in a multiorgan carcinogenesis bioassay of rats. These
      results support SMC and cysteine as chemopreventive agents for
      hepatocarcinogenesis and colon carcinogenesis. Their intake may be of importance
      for cancer.

PMID- 11238815
TI  - The influence of heating on the anticancer properties of garlic.
AB  - Allyl sulfur compounds are the major active constituents found in crushed garlic.
      Research has revealed that garlic and its lipid- or water-soluble components have
      many pharmacologic properties; however, studies also demonstrate that heating has
      a negative influence on these beneficial effects. We recently conducted several
      studies to investigate the influence of microwave or oven heating on the
      anticarcinogenesis property of garlic. Our studies showed that as little as 60 s
      of microwave heating or 45 min of oven heating can block garlic's ability to
      inhibit in vivo binding of mammary carcinogen [7,12-dimethylbenzene(a)anthracene
      (DMBA)] metabolites to rat mammary epithelial cell DNA. Allowing crushed garlic
      to "stand" for 10 min before microwave heating for 60 s prevented the total loss
      of anticarcinogenic activity. Our studies demonstrated that this blocking of the
      ability of garlic was consistent with inactivation of alliinase. These studies
      suggest that heating destroyed garlic's active allyl sulfur compound formation,
      which may relate to its anticancer properties.

PMID- 11238816
TI  - Antiproliferative effects of allium derivatives from garlic.
AB  - There is increasing evidence that allium derivatives from garlic have significant
      antiproliferative actions on human cancers. Both hormone-responsive and hormone
      unresponsive cells lines respond to these derivatives. The effects shown by
      allium derivatives include induction of apoptosis, regulation of cell cycle
      progression and modification of pathways of signal transduction. Allium
      derivatives appear to regulate nuclear factors involved in immune function and
      inflammation, as well as in cellular proliferation. Our own studies indicate that
      allium derivatives inhibit proliferation of the human prostate cancer cell line
      (LNCaP) and the human breast cancer cell line (MCF-7). Further research is
      required to clarify the mechanisms of inhibition of cellular proliferation by
      allium derivatives and to explore their potential application to cancer
      prevention and control.

PMID- 11238818
TI  - Enhanced immunocompetence by garlic: role in bladder cancer and other
      malignancies.
AB  - Of the many beneficial actions of garlic, inhibition of the growth of cancer is
      perhaps the most remarkable. Our previous animal studies demonstrated that aged
      garlic extract was highly effective, and unlike the approved immunotherapy for
      human bladder cancer, bacillus Calmette--Guerin (BCG), garlic was effective when
      added to the diet. To elucidate the mechanism of this antitumor effect, the
      literature describing antitumor and immune-enhancing effects of garlic is
      reviewed. Garlic can detoxify carcinogens by stimulation of cytochrome P(450)
      enzymes, antioxidant activity or sulfur compound binding. Studies demonstrate a
      direct toxic effect of garlic to sarcoma and gastric, colon, bladder and prostate
      cancer cells in tissue culture, but these effects cannot explain the inhibition
      of growth of transplanted cancer in animal models. The most likely explanation of
      this effect is immune stimulation. Comparison of the effects of garlic to BCG
      immunotherapy reveals many similarities. Both stimulate proliferation of
      lymphocytes and macrophage phagocytosis, induce the infiltration of macrophages
      and lymphocytes in transplanted tumors, induce splenic hypertrophy, stimulate
      release of interleukin-2, tumor necrosis factor-alpha and interferon-gamma,
      enhance natural killer cell, killer cell and lymphokine-activated killer cell
      activity. These activities represent effective stimulation of the immune
      response. Studies suggest that garlic may be useful in preventing the suppression
      of immune response that is associated with increased risk of malignancy. Data
      suggest that maintenance of immune stimulation can significantly reduce the risk
      of cancer. Clinical trials should be initiated to test the hypothesis that the
      immune stimulation and other beneficial effects of garlic are able to reduce the
      incidence of cancer.

PMID- 11238817
TI  - Possible mechanism by which allyl sulfides suppress neoplastic cell
      proliferation.
AB  - Both oil- and water-soluble allyl sulfur compounds from garlic have been found to
      possess antitumorigenic properties. These antitumorigenic properties increase as
      exposure increases both in vitro and in vivo. Generally, oil-soluble allyl sulfur
      compounds are more effective antiproliferative agents than their water-soluble
      counterparts. The ability of these compounds to suppress proliferation is
      associated with a depression in cell cycle progression and the induction of
      apoptosis. This depression in cell division coincides with an increase in the
      percentage of cells blocked in the G(2)/M phase of the cell cycle. A depression
      in p34(cdc2) kinase may account for this blockage in cell division.

PMID- 11238819
TI  - Alleviation by garlic of antitumor drug-induced damage to the intestine.
AB  - Antitumour drugs such as methotrexate (MTX) and 5-fluorouracil (5-FU) induce
      intestinal damage. This is a serious side effect of cancer chemotherapy. The
      present studies examined whether or not aged garlic extract (AGE) protects
      against damage from these antitumor drugs. Both drugs were administered orally
      for 4 or 5 d to rats fed a standard laboratory diet with and without 2% AGE. The
      small intestinal absorption of the poorly absorbable compound, fluorescein
      isothiocyanate--labeled dextran (FD-4; average molecular weight, 4400) was used
      to evaluate the damage to the intestine using the in vitro everted intestine
      technique and the in situ intestinal loop technique. FD-4 absorption increased in
      the antitumour drug-treated rats fed the diet without garlic. Interestingly, FD-4
      absorption was depressed in rats fed the diet containing AGE. These results
      suggest that AGE may protect the small intestine of rats from antitumour drug
      induced damage.

PMID- 11238820
TI  - Immunomodulatory effects of aged garlic extract.
AB  - Using various kinds of models, we examined the effects of aged garlic extract
      (AGE) on immune functions. In the immunoglobulin (Ig)E-mediated allergic mouse
      model, AGE significantly decreased the antigen-specific ear swelling induced by
      picryl chloride ointment to the ear and intravenous administration of
      antitrinitrophenyl antibody. In the transplanted carcinoma cell model, AGE
      significantly inhibited the growth of Sarcoma-180 (allogenic) and LL/2 lung
      carcinoma (syngenic) cells transplanted into mice. Concomitantly, increases in
      natural killer (NK) and killer activities of spleen cells were observed in
      Sarcoma-180--bearing mice administered AGE. In the psychological stress model,
      AGE significantly prevented the decrease in spleen weight and restored the
      reduction of anti-SRBC hemolytic plaque-forming cells caused by the electrical
      stress. These studies strongly suggest that AGE could be a promising candidate as
      an immune modifier, which maintains the homeostasis of immune functions; further
      studies are warranted to determine when it is most beneficial.

PMID- 11238821
TI  - Pharmacologic activities of aged garlic extract in comparison with other garlic
      preparations.
AB  - We investigated the pharmacologic activities of four garlic preparations, raw
      garlic juice (RGJ), heated garlic juice (HGJ), dehydrated garlic powder (DGP) and
      aged garlic extract (AGE). The study used three animal models, i.e., testicular
      hypogonadism (hypospermatogensis and impotence) induced by warm water treatment,
      intoxication of acetaldehyde and growth of inoculated tumor cells. RGJ was found
      to be effective only in recovery of testicular function. The efficacy of HGJ was
      observed in three models; however, it did not improve impotence. DGP was
      effective in recovery of spermatogenesis and stimulated acetaldehyde
      detoxification. Significant beneficial effects of AGE were found in all three
      models. Although all four garlic preparations significantly enhanced natural
      killer (NK) and killer cell activities of the spleen cells of tumor-bearing mice,
      only AGE and HGJ inhibited the growth of inoculated tumor cells. These results
      suggest that different types of garlic preparations have different pharmacologic
      properties, and among the four garlic preparations studied, AGE could be the most
      useful garlic preparation.

PMID- 11238822
TI  - In vitro effects of aged garlic extract and other nutritional supplements on
      sickle erythrocytes.
AB  - In the circulation of sickle cell anemia patients, a certain population of
      erythrocytes has an elevated density. These abnormally dense cells are believed
      to be at the root of the painful crisis and anemia of the patients. We have
      developed an in vitro method for the preparation of these heavier erythrocytes by
      a repeated deoxy-oxy cycling of erythrocytes from sickle cell anemia patients. By
      using this method, we studied whether certain nutritional supplements would
      inhibit the formation of dense cells in vitro. It was found that aged garlic
      extract (AGE) as well as its components with antioxidant activity, i.e., S
      allylcysteine and N alpha-(1-deoxy-D-fructos-1-yl)-L-arginine (fructosyl
      arginine), inhibited the formation of dense cells in vitro. Vitamin C, vitamin E
      and the spin-trapping agents, 5-diethoxyphophoryl-5-methyl-1-pyrroline-N-oxide
      and alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone were all found to inhibit the
      formation of dense cells in vitro. These results suggest that, when extremely
      stretched sickle-shaped cells are formed by the repeated deoxy-oxy cycling, the
      erythrocyte membrane becomes susceptible to oxidative injury by reactive oxygen
      species. The protection of the erythrocyte membrane from such an oxidative injury
      would prevent the membranes from becoming leaky to the calcium ion, thus
      inhibiting the activation of the calcium-activated potassium efflux channel and
      the formation of dense cells. We also developed a new ex vivo method of studying
      the possible efficacy of antioxidants taken orally on the dense cell formation in
      sickle cell patients. It involved the use of blood plasma taken from a healthy
      donor (with normal hemoglobin) of AB blood type who had consumed different types
      of antioxidants orally. By suspending sickle erythrocytes in such plasma and
      exposing them to the deoxy-oxy cycling, the degree of dense cell formation was
      determined. The degree of inhibition in vitro by antioxidants taken orally may be
      related to their efficacy in inhibiting dense cell formation in the patients. On
      the basis of these in vivo and ex vivo studies, we propose that a cocktail of
      antioxidants would have beneficial effects in lessening the incidence and
      severity of crisis and reducing anemia in sickle cell disease.

PMID- 11238823
TI  - Ameliorative effect of S-allylcysteine, a major thioallyl constituent in aged
      garlic extract, on learning deficits in senescence-accelerated mice.
AB  - This study examined the effect of S:-allylcysteine (SAC), a major thioallyl
      compound found in aged garlic extract, on the memory deficit and age-related
      changes of senescence-accelerated mice. Senescence-accelerated prone P8 mice fed
      a diet supplemented with 40 mg SAC/kg diet for 8 mo had a significantly
      attenuated decrease in the conditioned avoidance response compared with those not
      given SAC. In the elevated plus-maze test using senescence-accelerated prone P10
      mice, the percentage of time spent on the open arm was greater compared with the
      senescence-resistant control mice. Chronic dietary treatment with 40 mg SAC/kg
      diet decreased the time in the open arm in senescence-accelerated prone P10 mice.
      These studies suggest that diet supplementation with SAC may reduce age-related
      learning disabilities and cognitive disorders in senescence-accelerated mice.

PMID- 11238824
TI  - Isolation and characterization of the genes up-regulated in isolated neurons by
      aged garlic extract (AGE).
AB  - Aged garlic extract (AGE) produces neurotrophic effects on cultured fetal rat
      hippocampal neurons. These studies examined the molecular events triggered by AGE
      that might account for a suppression of neuronal cell death. Genes differentially
      expressed by the addition of AGE in primary cultured hippocampal neurons isolated
      from fetal rat brain were screened using mRNA differential display. Four cDNA
      clones were significantly enhanced at their transcriptional level; they were
      designated as #24, #110, #153 and #155. Quantitative reverse transcription
      polymerase chain reaction (RT-PCR), as well as dot-blot hybridization combined
      with RT-PCR, confirmed that the transcription from these four genes was elevated
      at least twofold, particularly the mRNA of #153, which was increased >20 times 72
      h after the addition of AGE. A homology search of the respective cDNA sequences
      in the DNA database revealed that #153 is an alpha 2-microglobulin-related
      protein (alpha 2MRP) gene. The others genes were not identified. Induction of the
      alpha 2MRP gene expression occurred within 24 h after addition of AGE. These
      findings suggest a possible mechanism by which AGE may regulate gene expression
      and bring about a neurotrophic effect. Further, our results suggest that alpha
      2MRP may function at the initial step of the molecular events triggered by AGE
      and play an important role in the survival of hippocampal neurons.

PMID- 11238825
TI  - S-allylcysteine inhibits free radical production, lipid peroxidation and neuronal
      damage in rat brain ischemia.
AB  - The efficacy of S-allylcysteine (SAC) as a free radical scavenger was studied
      using rat brain ischemia models. In a middle cerebral artery occlusion model,
      preischemic administration of SAC had the following effects: it improved motor
      performance and memory impairment and reduced water content and the infarct size.
      In a transient global ischemia model, the time course of free radical (alkoxyl
      radical) formation as studied by electron paramagnetic resonance (EPR)
      spectroscopy and alpha-phenyl-N-tert-butylnitrone (PBN) was biphasic; the first
      peak occurred at 5 min and the second at 20 min after reperfusion. Although SAC
      did not attenuate the first peak, it did affect the second peak, which is related
      to lipid peroxidation. The lipid peroxidation as estimated by thiobarbituric acid
      reactive substances (TBARS) increased significantly at 20 min after reperfusion.
      SAC decreased TBARS to the levels found without ischemia. These results suggest
      that SAC could have beneficial effects in brain ischemia and that the major
      protective mechanism may be the inhibition of free radical-mediated lipid
      peroxidation.

PMID- 11238826
TI  - Protection against Helicobacter pylori and other bacterial infections by garlic.
AB  - Louis Pasteur was the first to describe the antibacterial effect of onion and
      garlic juices. Historically, garlic has been used worldwide to fight bacterial
      infections. Allium vegetables, particularly garlic (Allium sativum L.) exhibit a
      broad antibiotic spectrum against both gram-positive and gram-negative bacteria.
      Noteworthy results published include the following: 1) raw juice of garlic was
      found to be effective against many common pathogenic bacteria-intestinal
      bacteria, which are responsible for diarrhea in humans and animals; 2) garlic is
      effective even against those strains that have become resistant to antibiotics;
      3) the combination of garlic with antibiotics leads to partial or total
      synergism; 4) complete lack of resistance has been observed repeatedly; 5) even
      toxin production by microorganisms is prevented by garlic. Helicobacter pylori
      (H. pylori) is a bacterium implicated in the etiology of stomach cancer and
      ulcers. The incidence of stomach cancer is lower in populations with a high
      intake of allium vegetables. We have demonstrated in vitro that H. pylori is
      susceptible to garlic extract at a fairly moderate concentration. Even some
      antibiotic-resistant H. pylori strains are susceptible to garlic. Clinical trials
      are necessary to explore the possibility of using garlic as a low-cost remedy for
      eradicating H. pylori.

PMID- 11238828
TI  - Dietary supplements: how they are used and regulated.
AB  - Overall use of nutrient and botanical dietary supplements (DS) has increased for
      years across all major categories. Many DS are simply taken as part of a healthy
      lifestyle, but some are used to reduce risk of or modulate risk factors for
      specific chronic diseases, such as heart disease (vitamin E, folic acid, garlic),
      cancer (selenium, vitamin E, garlic) and certain birth defects (folic acid).
      Other DS are used for short-term benefits such as sleep management (valerian,
      melatonin) and enhanced physical performance (pyruvate, creatine). DS are
      regulated under food law, but with certain provisions that apply only to DS.
      Thus, DS are eligible for Food and Drug Administration (FDA)-authorized health
      claims under the Nutrition and Labeling Education Act (NLEA). Health claims have
      already been authorized for folic acid and calcium, but not for several others.
      In 1994, when the Dietary Supplement Health and Education Act (DSHEA) was passed,
      it expanded and clarified the definition of DS, specified additional requirements
      for safety and provided for four types of claims of nutritional support. These
      include prevention of classic nutritional deficiencies, structure or function
      (S/F) effects, mechanisms for S/F effects and general well-being. Although S/F
      effects result from both foods and drugs, representation that a product will
      treat, cure, mitigate or diagnose a disease is reserved for drugs. Therefore, the
      wording of S/F claims for DS has become a difficult issue in the proposed DS
      labeling regulations.

PMID- 11238827
TI  - Effects of garlic preparations on the gastrointestinal mucosa.
AB  - The effects of garlic preparations, including dehydrated raw garlic powder (RGP),
      dehydrated boiled garlic powder (BGP) and aged garlic extract (AGE), on the
      gastric mucosa were determined using a newly established endoscopic air-powder
      delivery system, which can deliver solid materials directly into the stomach.
      Among the three preparations, RGP caused severe damage, including erosion. BGP
      also caused reddening of the mucosa, whereas AGE did not cause any undesirable
      effects. The safety of enteric-coated garlic products was also determined. Direct
      administration of pulverized enteric-coated products on the gastric mucosa caused
      reddening of the mucosa. When an enteric-coated tablet was administered orally,
      it caused loss of epithelial cells at the top of crypts in the ileum. These
      results suggest that caution be used with regard to safety and effectiveness when
      choosing a garlic preparation because some preparations may have undesirable
      effects, including gastrointestinal problems.

PMID- 11238829
TI  - A commentary on the effects of garlic extraction and formulation on product
      composition.
AB  - The garlic (Allium sativa L.) bulb has been used as a food and condiment for
      centuries throughout the entire world and in Egypt for perhaps 5000 years. Since
      the passage of the Dietary Supplement Health and Education Act (DSHEA) of 1994 by
      the U.S. Congress, it has been claimed that garlic dietary supplements possess
      health benefits. Support for this claim is not the primary objective of this
      publication. The primary objective of this article is to demonstrate that the
      prediction of a potential health benefit(s) from garlic is largely dependent on
      the process used to produce a product.

PMID- 11238830
TI  - Global harmonization of herbal health claims.
AB  - Over the past decade, herbal medicine has become a topic of increasing global
      importance, with both medical and economic implications. In developing countries,
      as much as 80% of the indigenous populations depends on traditional systems of
      medicine and medicinal plants as their primary source of healthcare. Within the
      European Community, herbal medicines represent an important share of the
      pharmaceutical market, with annual sales in the range of US$7 billion. In the
      United States, the sale of herbal products has skyrocketed from $200 million in
      1988 to >$3.3 billion in 1997. Such widespread use of botanicals throughout the
      world has raised serious questions concerning the quality, safety and efficacy of
      these products. Thus, accurate scientific assessment of herbal medicine is a
      prerequisite for global harmonization of herbal health claims. In 1995, as part
      of its overall global strategy of "Health for All" and due to numerous requests
      from the member states, the Traditional Medicine Program of the WHO began the
      extensive task of reviewing the world's scientific literature of commonly used
      herbal medicines and publishing this information in monographs. The WHO
      monographs are technical reviews of the quality, safety and efficacy of commonly
      used herbal medicines and are intended primarily to harmonize the proper use of
      herbal medicines throughout the world.

PMID- 11238832
TI  - Inhibition of major histocompatibility complex class II-dependent antigen
      presentation by neutralization of gamma interferon leads to breakdown of
      resistance against measles virus-induced encephalitis.
AB  - BALB/c mice are resistant to measles virus (MV)-induced encephalitis due to their
      strong MV-specific CD4(+) T-cell response. Resistance is broken by neutralization
      of gamma interferon with monoclonal antibodies, indicating an important role for
      this pleiotropic cytokine. Here, we demonstrate that mouse gamma interferon has
      no direct antiviral effect in vitro and in vivo. The breakdown of resistance is
      due neither to a switch in the T-helper response nor to an impaired migration of
      CD4(+) T cells. Neutralization of gamma interferon interferes with the major
      histocompatibility complex class II-dependent antigen presentation and subsequent
      proliferation of CD4(+) T cells in vitro and in vivo. In consequence, the
      reduction in numbers of CD4(+) T cells below a protective threshold leads to
      susceptibility to MV-induced encephalitis.

PMID- 11238833
TI  - African swine fever virus multigene family 360 and 530 genes are novel macrophage
      host range determinants.
AB  - Pathogenic African swine fever virus (ASFV) isolates primarily target cells of
      the mononuclear-phagocytic system in infected swine and replicate efficiently in
      primary macrophage cell cultures in vitro. ASFVs can, however, be adapted to grow
      in monkey cell lines. Characterization of two cell culture-adapted viruses, MS16
      and BA71V, revealed that neither virus replicated in macrophage cell cultures.
      Cell viability experiments and ultrastructural analysis showed that infection
      with these viruses resulted in early macrophage cell death, which occurred prior
      to viral progeny production. Genomic cosmid clones from pathogenic ASFV isolate
      E70 were used in marker rescue experiments to identify sequences capable of
      restoring MS16 and BA71V growth in macrophage cell cultures. A cosmid clone
      representing a 38-kbp region at the left terminus of the genome completely
      restored the growth of both viruses. In subsequent fine-mapping experiments, an
      11-kbp subclone from this region was sufficient for complete rescue of BA71V
      growth. Sequence analysis indicated that both MS16 and BA71V had significant
      deletions in the region containing members of multigene family 360 (MGF 360) and
      MGF530. Deletion of this same region from highly pathogenic ASFV isolate Pr4
      significantly reduced viral growth in macrophage cell cultures. These findings
      indicate that ASFV MGF360 and MGF530 genes perform an essential macrophage host
      range function(s) that involves promotion of infected-cell survival.

PMID- 11238834
TI  - Herpes simplex virus-induced keratitis: evaluation of the role of molecular
      mimicry in lesion pathogenesis.
AB  - Viruses are suspected but usually unproven triggering factors in autoimmunity.
      One favored mechanism to explain the role of viruses in the genesis of
      autoimmunity is molecular mimicry. An immunoinflammatory blinding lesion called
      herpetic stromal keratitis (HSK) that follows ocular infection with herpes
      simplex virus (HSV) is suggested to result from a CD4(+) T-cell response to a UL6
      peptide of HSV that cross-reacts with a corneal autopeptide shared with the
      immunoglobulin G2a(b) (IgG2a(b)) isotype. The present report reevaluates the
      molecular mimicry hypothesis to explain HSK pathogenesis. Our results failed to
      reveal cross-reactivity between the UL6 and IgG2a(b) peptides or between peptide
      reactive T cells and HSV antigens. More importantly, animals infected with HSV
      failed to develop responses that reacted with either peptide, and infection with
      a recombinant vaccinia UL6 vector failed to cause HSK, in spite of generating UL6
      reactivity. Other lines of evidence also failed to support the molecular mimicry
      hypothesis, such as the failure to affect HSK severity upon tolerization of
      susceptible BALB/c and B-cell-deficient mice with IgG2a(b) or UL6 peptides. An
      additional study system revealed that HSK could be induced in mouse strains, such
      as the OT2 x RAG1(-/-) mice (T cell receptor transgenic recognizing OVA(323-339))
      that were unable to produce CD4(+) T-cell responses to any detectable HSV
      antigens. Our results cast doubt on the molecular mimicry hypothesis as an
      explanation for the pathogenesis of HSK and indicate that if autoimmunity is
      involved its likely proceeds via a bystander activation mechanism.

PMID- 11238835
TI  - "Hit-and-run" transformation by adenovirus oncogenes.
AB  - According to classical concepts of viral oncogenesis, the persistence of virus
      specific oncogenes is required to maintain the transformed cellular phenotype. In
      contrast, the "hit-and-run" hypothesis claims that viruses can mediate cellular
      transformation through an initial "hit," while maintenance of the transformed
      state is compatible with the loss ("run") of viral molecules. It is well
      established that the adenovirus E1A and E1B gene products can cooperatively
      transform primary human and rodent cells to a tumorigenic phenotype and that
      these cells permanently express the viral oncogenes. Additionally, recent studies
      have shown that the adenovirus E4 region encodes two novel oncoproteins, the
      products of E4orf6 and E4orf3, which cooperate with the viral E1A proteins to
      transform primary rat cells in an E1B-like fashion. Unexpectedly, however, cells
      transformed by E1A and either E4orf6 or E4orf3 fail to express the viral E4 gene
      products, and only a subset contain E1A proteins. In fact, the majority of these
      cells lack E4- and E1A-specific DNA sequences, indicating that transformation
      occurred through a hit-and-run mechanism. We provide evidence that the unusual
      transforming activities of the adenoviral oncoproteins may be due to their
      mutagenic potential. Our results strongly support the possibility that even
      tumors that lack any detectable virus-specific molecules can be of viral origin,
      which could have a significant impact on the use of adenoviral vectors for gene
      therapy.

PMID- 11238836
TI  - Inhibitors of human immunodeficiency virus type 1 reverse transcriptase target
      distinct phases of early reverse transcription.
AB  - Early HIV-1 reverse transcription can be separated into initiation and elongation
      phases. Here we show, using PCR analysis of negative-strand strong-stop DNA [(
      )ssDNA] synthesis in intact virus, that different reverse transcriptase (RT)
      inhibitors affect distinct phases of early natural endogenous reverse
      transcription (NERT). The effects of nevirapine on NERT were consistent with a
      mechanism of action including both specific and nonspecific binding events. The
      nonspecific component of this inhibition targeted the elongation reaction,
      whereas the specific effect seemed principally to be directed at very early
      events (initiation or the initiation-elongation switch). In contrast, foscarnet
      and the nucleoside analog ddATP inhibited both early and late (-)ssDNA synthesis
      in a similar manner. We also examined compounds that targeted other viral
      proteins and found that Ro24-7429 (a Tat antagonist) and rosmarinic acid (an
      integrase inhibitor) also directly inhibited RT. Our results indicate that NERT
      can be used to identify and evaluate compounds that directly target the reverse
      transcription complex.

PMID- 11238837
TI  - Highly reliable heterologous system for evaluating resistance of clinical herpes
      simplex virus isolates to nucleoside analogues.
AB  - Clinical resistance of herpes simplex virus (HSV) types 1 and 2 to acyclovir
      (ACV) is usually caused by the presence of point mutations within the coding
      region of the viral thymidine kinase (TK) gene. The distinction between viral TK
      mutations involved in ACV resistance or part of viral polymorphism can be
      difficult to evaluate with current methodologies based on transfection and
      homologous recombination. We have developed and validated a new heterologous
      system based on the expression of the viral TK gene by the protozoan parasite
      Leishmania, normally devoid of TK activity. The viral TK genes from 5 ACV
      susceptible and 13 ACV-resistant clinical HSV isolates and from the reference
      strains MS2 (type 2) and KOS (type 1) were transfected as part of an episomal
      expression vector in Leishmania. The susceptibility of TK-recombinant parasites
      to ganciclovir (GCV), a closely related nucleoside analogue, was evaluated by a
      simple measurement of the absorbance of Leishmania cultures grown in the presence
      of the drug. Expression of the TK gene from ACV-susceptible clinical isolates
      resulted in Leishmania susceptibility to GCV, whereas expression of a TK gene
      with frameshift mutations or nucleotide substitutions from ACV-resistant isolates
      gave rise to parasites with high levels of GCV resistance. The expression of the
      HSV TK gene in Leishmania provides an easy, reliable, and sensitive assay for
      evaluating HSV susceptibility to nucleoside analogues and for assessing the role
      of specific viral TK mutations.

PMID- 11238838
TI  - Phenotypic characterization of three phylogenetically conserved stem-loop motifs
      in the mengovirus 3' untranslated region.
AB  - An alignment of cardiovirus sequences led to the prediction of three conserved
      stem-loops in the 3' untranslated region (UTR) of mengovirus. Deletions of each
      stem were engineered in mengovirus cDNAs and also in mengovirus replicons, in
      which part of the viral capsid sequences were replaced with the firefly
      luciferase gene. The effect of deletion on RNA infectivity and plaque phenotype
      was evaluated after transfection of viral transcripts into HeLa cells or by
      luciferase assays of cellular extracts after transfection with RNA replicons.
      Stem I (mengovirus bases 7666 to 7687) was found to be dispensable for viral
      growth or exponential luciferase expression. Deletion of stem III (bases 7711 to
      7721) was lethal to the virus, and the replicons were incapable of RNA synthesis.
      Deletion of stem II (DeltaII; bases 7692 to 7705) produced an intermediate
      phenotype, in that replicons had marginal RNA synthesis activity but transfection
      with genomic RNA usually failed to produce plaques after normal incubation times
      (31 h, 37 degrees C). In a few of the DeltaII transfections, however, plaques
      were observed after long incubation, especially if the cells received large
      amounts of RNA (3 microg per 3 x 10(6) cells). Viruses from two DeltaII-derived
      plaques were isolated and amplified. Their RNAs were converted into cDNA,
      sequenced, and mapped for genotype. Each maintained the DeltaII deletion and, in
      addition, had one or two reversion mutations, which were characterized by reverse
      genetics as responsible for the phenotypes. One reversion caused an amino acid
      change in the polymerase (3D(pol)), and the other was localized to the 3' UTR,
      upstream of stem I.

PMID- 11238839
TI  - Computational analysis of retrovirus-induced scid cell death.
AB  - It was shown recently that retroviral infection induces integrase-dependent
      apoptosis (programmed cell death) in DNA-dependent protein kinase (DNA-PK)
      deficient scid pre-B cell lines, and it has been proposed that retroviral DNA
      integration is perceived as DNA damage that is repairable by the DNA-PK-dependent
      nonhomologous end-joining pathway (R. Daniel, R. A. Katz, and A. M. Skalka,
      Science 284:644-647, 1999). Very few infectious virions seem to be necessary to
      induce scid cell death. In this study, we used a modeling approach to estimate
      the number of integration events necessary to induce cell death of DNA-PK
      deficient scid cells. Several models for integration-mediated cell killing were
      considered. Our analyses indicate that a single hit (integration event) is
      sufficient to kill a scid cell. Moreover, the closest fit between the
      experimental data and our computational simulations was achieved with a model in
      which the infected scid cell must pass through S phase to trigger apoptosis. This
      model is consistent with the findings that a single double-strand DNA break is
      sufficient to kill a cell deficient in DNA repair and illustrates the potential
      of a modeling approach to address quantitative aspects of virus-cell
      interactions.

PMID- 11238840
TI  - Transcription activation of polyadenylated nuclear rna by rta in human
      herpesvirus 8/Kaposi's sarcoma-associated herpesvirus.
AB  - Human herpesvirus 8 (HHV-8) (also known as Kaposi's sarcoma-associated
      herpesvirus) encodes a novel noncoding polyadenylated nuclear (PAN) RNA (also
      known as T1.1 or nut-1) during the early phase of lytic replication. PAN RNA is
      the most abundant transcript of HHV-8, comprising 80% of total poly(A)-selected
      transcripts in HHV-8-infected cells during lytic replication. We directly
      measured the abundance of PAN RNA by visualizing 1.1- to 1.2- kb PAN RNA in an
      ethidium bromide-stained gel from poly(A)-selected RNA. We further pursued the
      mechanisms by which PAN RNA expression is induced to such high levels. rta, an
      immediate-early gene of HHV-8, is a transactivator that is sufficient and
      necessary to activate lytic gene expression in latently infected cells. Ectopic
      expression of Rta was previously shown to induce PAN RNA expression from the
      endogenous viral genome and activate the PAN promoter in a reporter system. Here,
      we have identified the Rta-responsive element (RRE) in the PAN promoter. Deletion
      analysis revealed that the RRE is present in a region between nucleotides -69 and
      -38 of the PAN promoter. A promoter construct containing the 69 nucleotides
      upstream of the transcription start site of the PAN promoter was activated by Rta
      in the absence or presence of the HHV-8 genome. Rta activated the PAN promoter up
      to 7,000-fold in 293T cells and 2,000-fold in B cells. Electrophoretic mobility
      shift assays demonstrated that Rta formed a highly stable complex with the RRE of
      the PAN promoter. Our study suggests that Rta can induce PAN RNA expression by
      direct binding of Rta to the RRE of the PAN promoter. This study has highlighted
      an important mechanism controlling PAN RNA expression and also provides a model
      system for investigating how Rta transactivates gene expression during lytic
      replication.

PMID- 11238841
TI  - Mouse-human heterokaryons support efficient human immunodeficiency virus type 1
      assembly.
AB  - Murine cells do not support human immunodeficiency virus type 1 (HIV-1)
      replication because of blocks to virus entry, proviral expression, and virion
      assembly. In murine 3T3 fibroblasts, the block to HIV-1 entry is relieved by the
      introduction of human CD4 and CCR5 or CXCR4, and proviral expression is increased
      by the introduction of the Tat cofactor, human cyclin T1; however, because of the
      assembly block, virus fails to spread. A panel of rodent cell lines expressing
      human CD4, CCR5, and cyclin T1 was established and studied for the ability to
      support virus replication. Mus musculus lymphoid cell lines EL4 and L1-2 and Mus
      dunni fibroblasts supported only low levels of virus assembly and released small
      amounts of infectious virus. CHO and Rat2 cell lines produced more infectious
      virus, but this production was still 40-fold lower than production in human
      cells. Only CHO cells expressing the three human cofactors were partially
      permissive for HIV-1 replication. To investigate the basis of the block to HIV-1
      assembly, mouse-human heterokaryons were tested for ability to assemble and
      release virus. Fusion of human cells to HIV-1-infected mouse cells expressing
      CD4, CCR5, and cyclin T1 caused a 12-fold increase in virion release and a 700
      fold increase in infectious virus production. Fusion of HIV-1-infected M. dunni
      tail fibroblasts to uninfected human cells caused a similar increase in virus
      release. More efficient virus release was not caused by increased proviral
      transcription or increased synthesis of virion components. Analysis of reciprocal
      heterokaryons suggested the absence of an inhibitor of virus assembly. Taken
      together, the results suggested that murine fibroblasts lack a cofactor that is
      required for efficient virus assembly and release.

PMID- 11238842
TI  - Role of natural killer cells in resistance against friend retrovirus-induced
      leukemia.
AB  - We have previously shown that immunization with a synthetic peptide that contains
      a single CD4(+) T-cell epitope protects mice against immunosuppressive Friend
      retrovirus infection. Cells producing infectious Friend virus were rapidly
      eliminated from the spleens of mice that had been immunized with the single
      epitope peptide. However, actual effector mechanisms induced through T-helper
      cell responses after Friend virus inoculation were unknown. When cytotoxic
      effector cells detected in the early phase of Friend retrovirus infection were
      separated based on their expression of cell surface markers, those lacking CD4
      and CD8 but expressing natural killer cell markers were found to constitute the
      majority of effector cells that lysed Friend virus-induced leukemia cells.
      Depletion of natural killer cells by injecting anti-asialo-ganglio-N
      tetraosylceramide antibody did not affect the number of CD4(+) or CD8(+) T cells
      in the spleen, virus antigen-specific proliferative responses of CD4(+) T cells,
      or cytotoxic activity against Friend virus-induced leukemia cells exerted by
      CD8(+) effector cells. However, the same treatment markedly reduced the killing
      activity of CD4(-) CD8(-) effector cells and completely abolished the effect of
      peptide immunization. Although the above enhancement of natural killer cell
      activity in the early stage of Friend virus infection was also observed in mice
      given no peptide, these results have demonstrated the importance and requirement
      of natural killer cells in vaccine-induced resistance against the retroviral
      infection.

PMID- 11238843
TI  - Identification of T-cell epitopes in nonstructural proteins of foot-and-mouth
      disease virus.
AB  - Porcine T-cell recognition of foot-and-mouth disease virus (FMDV) nonstructural
      proteins (NSP) was tested using in vitro lymphoproliferative responses.
      Lymphocytes were obtained from outbred pigs experimentally infected with FMDV. Of
      the different NSP, polypeptides 3A, 3B, and 3C gave the highest stimulations in
      the in vitro assays. The use of overlapping synthetic peptides allowed the
      identification of amino acid regions within these proteins that were efficiently
      recognized by the lymphocytes. The sequences of some of these antigenic peptides
      were highly conserved among different FMDV serotypes. They elicited major
      histocompatibility complex-restricted responses with lymphocytes from pigs
      infected with either a type C virus or reinfected with a heterologous FMDV. A
      tandem peptide containing the T-cell peptide 3A[21-35] and the B-cell antigenic
      site VP1[137-156] also efficiently stimulated lymphocytes from infected animals
      in vitro. Furthermore, this tandem peptide elicited significant levels of
      serotype-specific antiviral activity, a result consistent with the induction of
      anti-FMDV antibodies. Thus, inclusion in the peptide formulation of a T-cell
      epitope derived from the NSP 3A possessing the capacity to induce T helper
      activity can allow cooperative induction of anti-FMDV antibodies by B cells.

PMID- 11238844
TI  - Kaposi's sarcoma-associated herpesvirus K-bZIP protein is phosphorylated by
      cyclin-dependent kinases.
AB  - The K8 locus in Kaposi's sarcoma-associated herpesvirus (KSHV) is syntenic with
      the Epstein-Barr virus (EBV) BZLF (Z) locus and expresses three alternatively
      spliced transcripts. The fully spliced transcript encodes K-bZIP, the KSHV
      homologue of the EBV immediate-early transcriptional transactivator Z. Here we
      show that despite the presence of alternatively spliced transcripts, the protein
      from the fully spliced RNA, K-bZIP, is the principal product detectable in KSHV
      infected B cells. The protein is detected only in lytically infected cells and is
      localized to the nucleus. We further characterized K-bZIP by determining its
      phosphorylation status. Phosphoamino acid analysis revealed phosphorylation on
      serine and threonine. Analysis of the sites of K-bZIP phosphorylation by tandem
      mass spectrometry revealed that K-bZIP was phosphorylated on Thr 111 and Ser 167.
      These phosphorylation sites are contained within cyclin-dependent kinase (CDK)
      recognition sites with the consensus sequence (S/T)PXR, suggesting that K-bZIP
      could be phosphorylated by CDKs. We tested this hypothesis using an in vitro
      kinase reaction performed in whole-cell extracts that resemble in vivo conditions
      more closely than standard in vitro kinase reactions. We found that the three CDK
      cyclin complexes we tested phosphorylated K-bZIP but not the control ORF 73
      protein, which contains four (S/T)PXR sites. Ectopic expression of K-bZIP cannot
      reactivate KSHV from latency, and single and double mutants of K-bZIP in which
      alanines replaced the phosphorylated serine and/or threonine also failed to
      induce lytic replication. These studies indicate that K-bZIP is a substrate for
      CDKs and should inform further functional analyses of the protein.

PMID- 11238845
TI  - Vaccinia virus blocks gamma interferon signal transduction: viral VH1 phosphatase
      reverses Stat1 activation.
AB  - We have analyzed the effects of vaccinia virus (VV) on gamma interferon (IFN
      gamma) signal transduction. Infection of cells with VV 1 to 2 h prior to
      treatment with IFN-gamma inhibits phosphorylation and nuclear translocation of
      Stat1 and consequently blocks accumulation of mRNAs normally induced by IFN
      gamma. While phosphorylation of other proteins in the IFN-gamma pathway was not
      affected, activation of Stat1 by other ligand-receptor systems was also blocked
      by VV. This block of Stat1 activation was dose dependent, and although viral
      protein synthesis was not required, entry and uncoating of viral cores appear to
      be needed to block the accumulation of phosphorylated Stat1. These results
      suggest that a virion component is responsible for the effect. VV virions contain
      a phosphatase (VH1) that is sensitive to the phosphatase inhibitor Na(3)VO(4) but
      not to okadaic acid. Addition of Na(3)VO(4) but not okadaic acid restored normal
      Stat1 phosphorylation levels in VV-infected cells. Moreover, virions containing
      reduced levels of VH1 were unable to block the IFN-gamma signaling pathway. In
      vitro studies show that the phosphatase can bind and dephosphorylate Stat1,
      indicating that this transcription factor can be a substrate for VH1. Our results
      reveal a novel mechanism by which VV interferes with the onset of host immune
      responses by blocking the IFN-gamma signal cascade through the dephosphorylating
      activity of the viral phosphatase VH1.

PMID- 11238846
TI  - Adaptation of reovirus to growth in the presence of protease inhibitor E64
      segregates with a mutation in the carboxy terminus of viral outer-capsid protein
      sigma3.
AB  - Reovirus virions are internalized into cells by receptor-mediated endocytosis.
      Within the endocytic compartment, the viral outer capsid undergoes acid-dependent
      proteolysis leading to degradation of sigma3 protein and proteolytic cleavage of
      micro1/micro1C protein. E64 is a specific inhibitor of cysteine-containing
      proteases that blocks disassembly of reovirus virions. To identify domains in
      reovirus proteins that influence susceptibility to E64-mediated inhibition of
      disassembly, we selected variant viruses by serial passage of strain type 3
      Dearing (T3D) in murine L929 cells treated with E64. E64-adapted variant viruses
      (D-EA viruses) produced 7- to 17-fold-greater yields than T3D did after infection
      of cells treated with 100 microM E64. Viral genes that segregate with growth of D
      EA viruses in the presence of E64 were identified by using reassortant viruses
      isolated from independent crosses of E64-sensitive strain type 1 Lang and two
      prototype D-EA viruses. Growth of reassortant viruses in the presence of E64
      segregated with the S4 gene, which encodes outer-capsid protein sigma3. Sequence
      analysis of S4 genes of three D-EA viruses isolated from independent passage
      series revealed a common tyrosine-to-histidine mutation at amino acid 354 in the
      deduced amino acid sequence of sigma3. Proteolysis of D-EA virions by endocytic
      protease cathepsin L occurred with faster kinetics than proteolysis of wild-type
      T3D virions. Treatment of D-EA virions, but not T3D virions, with cathepsin D
      resulted in proteolysis of sigma3, a property that also was found to segregate
      with the D-EA S4 gene. These results indicate that a region in sigma3 protein
      containing amino acid 354 influences susceptibility of sigma3 to proteolysis
      during reovirus disassembly.

PMID- 11238848
TI  - Purification and characterization of West Nile virus nucleoside triphosphatase
      (NTPase)/helicase: evidence for dissociation of the NTPase and helicase
      activities of the enzyme.
AB  - The nucleoside triphosphatase (NTPase)/helicase associated with nonstructural
      protein 3 of West Nile (WN) virus was purified from cell culture medium harvested
      from virus-infected Vero cells. The purification procedure included sequential
      chromatography on Superdex-200 and Reactive Red 120 columns, followed by a
      concentration step on an Ultrogel hydroxyapatite column. The nature of the
      purified protein was confirmed by immunoblot analysis using a WN virus-positive
      antiserum, determination of its NH(2) terminus by microsequencing, and a binding
      assay with 5'-[(14)C]fluorosulfonylbenzoyladenosine. Under optimized reaction
      conditions the enzyme catalyzed the hydrolysis of ATP and the unwinding of the
      DNA duplex with k(cat) values of 133 and 5.5 x 10(-3) s(-1), respectively.
      Characterization of the NTPase activity of the WN virus enzyme revealed that
      optimum conditions with respect to the Mg(2+) requirement and the monovalent salt
      or polynucleotide response differed from those of other flavivirus NTPases.
      Initial kinetic studies demonstrated that the inhibition (or activation) of
      ATPase activity by ribavirin-5'-triphosphate is not directly related to changes
      in the helicase activity of the enzyme. Further analysis using guanine and O(6)
      benzoylguanine derivatives revealed that the ATPase activity of WN virus
      NTPase/helicase may be modulated, i.e., increased or reduced, with no effect on
      the helicase activity of the enzyme. On the other hand the helicase activity
      could be modulated without changing the ATPase activity. Our observations show
      that the number of ATP hydrolysis events per unwinding cycle is not a constant
      value.

PMID- 11238847
TI  - Brome mosaic virus Protein 1a recruits viral RNA2 to RNA replication through a 5'
      proximal RNA2 signal.
AB  - Brome mosaic virus (BMV), a positive-strand RNA virus in the alphavirus-like
      superfamily, encodes two RNA replication factors. Membrane-associated 1a protein
      contains a helicase-like domain and RNA capping functions. 2a, which is targeted
      to membranes by 1a, contains a central polymerase-like domain. In the absence of
      2a and RNA replication, 1a acts through an intergenic replication signal in BMV
      genomic RNA3 to stabilize RNA3 and induce RNA3 to associate with cellular
      membrane. Multiple results imply that 1a-induced RNA3 stabilization reflects
      interactions involved in recruiting RNA3 templates into replication. To determine
      if 1a had similar effects on another BMV RNA replication template, we constructed
      a plasmid expressing BMV genomic RNA2 in vivo. In vivo-expressed RNA2 templates
      were replicated upon expression of 1a and 2a. In the absence of 2a, 1a stabilized
      RNA2 and induced RNA2 to associate with membrane. Deletion analysis demonstrated
      that 1a-induced membrane association of RNA2 was mediated by sequences in the 5'
      proximal third of RNA2. The RNA2 5' untranslated region was sufficient to confer
      1a-induced membrane association on a nonviral RNA. However, sequences in the N
      terminal region of the 2a open reading frame enhanced 1a responsiveness of RNA2
      and a chimeric RNA. A 5'-terminal RNA2 stem-loop important for RNA2 replication
      was essential for 1a-induced membrane association of RNA2 and, like the 1a
      responsive RNA3 intergenic region, contained a required box B motif corresponding
      to the TPsiC stem-loop of host tRNAs. The level of 1a-induced membrane
      association of various RNA2 mutants correlated well with their abilities to serve
      as replication templates. These results support and expand the conclusion that 1a
      induced BMV RNA stabilization and membrane association reflect early, 1a-mediated
      steps in viral RNA replication.

PMID- 11238849
TI  - Amino-terminal domain exchange redirects origin-specific interactions of adeno
      associated virus rep78 in vitro.
AB  - The unique ability of adeno-associated virus type 2 (AAV) to site-specifically
      integrate its genome into a defined sequence on human chromosome 19 (AAVS1) makes
      it of particular interest for use in targeted gene delivery. The objective
      underlying this study is to provide evidence for the feasibility of retargeting
      site-specific integration into selected loci within the human genome. Current
      models postulate that AAV DNA integration is initiated through the interactions
      of the products of a single viral open reading frame, REP, with sequences present
      in AAVS1 that resemble the minimal origin for AAV DNA replication. Here, we
      present a cell-free system designed to dissect the Rep functions required to
      target site-specific integration using functional chimeric Rep proteins derived
      from AAV Rep78 and Rep1 of the closely related goose parvovirus. We show that
      amino-terminal domain exchange efficiently redirects the specificity of Rep to
      the minimal origin of DNA replication. Furthermore, we establish that the amino
      terminal 208 amino acids of Rep78/68 constitute a catalytic domain of Rep
      sufficient to mediate site-specific endonuclease activity.

PMID- 11238850
TI  - ICP0 is required for efficient reactivation of herpes simplex virus type 1 from
      neuronal latency.
AB  - Relative to wild-type herpes simplex virus type 1 (HSV-1), ICP0-null mutant
      viruses reactivate inefficiently from explanted, latently infected mouse
      trigeminal ganglia (TG), indicating that ICP0 is not essential for reactivation
      but plays a central role in enhancing the efficiency of reactivation. The
      validity of these findings has been questioned, however, because the replication
      of ICP0-null mutants is impaired in animal models during the establishment of
      latency, such that fewer mutant genomes than wild-type genomes are present in
      latently infected mouse TG. Therefore, the reduced number of mutant viral genomes
      available to reactivate, rather than mutations in the ICP0 gene per se, may be
      responsible for the reduced reactivation efficiency of ICP0-null mutants. We have
      recently demonstrated that optimization of the size of the ICP0 mutant virus
      inoculum and transient immunosuppression of mutant-infected mice with
      cyclophosphamide can be used to establish wild-type levels of ICP0-null mutant
      genomes in latently infected TG (W. P. Halford and P. A. Schaffer, J. Virol.
      74:5957-5967, 2000). Using this procedure to equalize mutant and wild-type genome
      numbers, the goal of the present study was to determine if, relative to wild-type
      virus, the absence of ICP0 function in two ICP0-null mutants, n212 and 7134,
      affects reactivation efficiency from (i) explants of latently infected TG and
      (ii) primary cultures of latently infected TG cells. Although equivalent numbers
      of viral genomes were present in TG of mice latently infected with either wild
      type or mutant viruses, reactivation of n212 and 7134 from heat-stressed TG
      explants was inefficient (31 and 37% reactivation, respectively) relative to
      reactivation of wild-type virus (KOS) (95%). Similarly, n212 and 7134 reactivated
      inefficiently from primary cultures of dissociated TG cells plated directly after
      removal from the mouse (7 and 4% reactivation, respectively), relative to KOS
      (60% reactivation). The efficiency and kinetics of reactivation of KOS, n212, and
      7134 from cultured TG cells (treated with acyclovir to facilitate the
      establishment of latency) in response to heat stress or superinfection with a
      nonreplicating HSV-1 ICP4(-) mutant, n12, were compared. Whereas heat stress
      induced reactivation of KOS from 69% of latently infected TG cell cultures,
      reactivation of n212 and 7134 was detected in only 1 and 7% of cultures,
      respectively. In contrast, superinfection with the ICP4(-) virus, which expresses
      high levels of ICP0, resulted in the production of infectious virus in nearly
      100% of cultures latently infected with KOS, n212, or 7134 within 72 h. Thus,
      although latent mutant viral genome loads were equivalent to that of wild-type
      virus, in the absence of ICP0, n212 and 7134 reactivated inefficiently from
      latently infected TG cells during culture establishment and following heat
      stress. Collectively, these findings demonstrate that ICP0 is required to induce
      efficient reactivation of HSV-1 from neuronal latency.

PMID- 11238851
TI  - Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen 1
      mediates episome persistence through cis-acting terminal repeat (TR) sequence and
      specifically binds TR DNA.
AB  - Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) (also known as human
      herpesvirus 8) latently infects KS tumors, primary effusion lymphomas (PELs), and
      PEL cell lines. In latently infected cells, KSHV DNA is maintained as
      circularized, extrachromosomal episomes. To persist in proliferating cells, KSHV
      episomes must replicate and efficiently segregate to progeny nuclei. In
      uninfected B-lymphoblastoid cells, KSHV latency-associated nuclear antigen
      (LANA1) is necessary and sufficient for persistence of artificial episomes
      containing specific KSHV DNA. In previous work, the cis-acting sequence required
      for episome persistence contained KSHV terminal-repeat (TR) DNA and unique KSHV
      sequence. We now show that cis-acting KSHV TR DNA is necessary and sufficient for
      LANA1-mediated episome persistence. Furthermore, LANA1 binds TR DNA in mobility
      shift assays and a 20-nucleotide LANA1 binding sequence has been identified.
      Since LANA1 colocalizes with KSHV episomes along metaphase chromosomes, these
      results are consistent with a model in which LANA1 may bridge TR DNA to
      chromosomes during mitosis to efficiently segregate KSHV episomes to progeny
      nuclei.

PMID- 11238852
TI  - Human immunodeficiency virus seroconversion and evolution of the hepatitis C
      virus quasispecies.
AB  - When chronic hepatitis C virus (HCV) infections are complicated by acquisition of
      human immunodeficiency virus (HIV), liver disease appears to accelerate and serum
      levels of HCV RNA may rise. We hypothesized that HIV might affect the HCV
      quasispecies by decreasing both complexity (if HIV-induced immunosuppression
      lessens pressure for selecting HCV substitutions) and the ratio of nonsynonymous
      (d(N)) to synonymous (d(S)) substitutions, because d(N) may be lower (if there is
      less selective pressure). To test this hypothesis, we studied the evolution of
      HCV sequences in 10 persons with chronic HCV infection who seroconverted to HIV
      and, over the next 3 years, had slow or rapid progression of HIV-associated
      disease. From each subject, four serum specimens were selected with reference to
      HIV seroconversion: (i) more than 2 years prior, (ii) less than 2 years prior,
      (iii) less than 2 years after, and (iv) more than 2 years after. The HCV
      quasispecies in these specimens was characterized by generating clones containing
      1 kb of cDNA that spanned the E1 gene and the E2 hypervariable region 1 (HVR1),
      followed by analysis of clonal frequencies (via electrophoretic migration) and
      nucleotide sequences. We examined 1,320 cDNA clones (33 per time point) and 287
      sequences (median of 7 per time point). We observed a trend toward lower
      d(N)/d(S) after HIV seroconversion in 7 of 10 subjects and lower d(N)/d(S) in
      those with rapid HIV disease progression. However, the magnitude of these
      differences was small. These results are consistent with the hypothesis that HIV
      infection alters the HCV quasispecies, but the number of subjects and observation
      time may be too low to characterize the full effect.

PMID- 11238853
TI  - Evidence of two Lyssavirus phylogroups with distinct pathogenicity and
      immunogenicity.
AB  - The genetic diversity of representative members of the Lyssavirus genus (rabies
      and rabies-related viruses) was evaluated using the gene encoding the
      transmembrane glycoprotein involved in the virus-host interaction,
      immunogenicity, and pathogenicity. Phylogenetic analysis distinguished seven
      genotypes, which could be divided into two major phylogroups having the highest
      bootstrap values. Phylogroup I comprises the worldwide genotype 1 (classic Rabies
      virus), the European bat lyssavirus (EBL) genotypes 5 (EBL1) and 6 (EBL2), the
      African genotype 4 (Duvenhage virus), and the Australian bat lyssavirus genotype
      7. Phylogroup II comprises the divergent African genotypes 2 (Lagos bat virus)
      and 3 (Mokola virus). We studied immunogenic and pathogenic properties to
      investigate the biological significance of this phylogenetic grouping. Viruses
      from phylogroup I (Rabies virus and EBL1) were found to be pathogenic for mice
      when injected by the intracerebral or the intramuscular route, whereas viruses
      from phylogroup II (Mokola and Lagos bat viruses) were only pathogenic by the
      intracerebral route. We showed that the glycoprotein R333 residue essential for
      virulence was naturally replaced by a D333 in the phylogroup II viruses, likely
      resulting in their attenuated pathogenicity. Moreover, cross-neutralization
      distinguished the same phylogroups. Within each phylogroup, the amino acid
      sequence of the glycoprotein ectodomain was at least 74% identical, and
      antiglycoprotein virus-neutralizing antibodies displayed cross-neutralization.
      Between phylogroups, the identity was less than 64.5% and the cross
      neutralization was absent, explaining why the classical rabies vaccines
      (phylogroup I) cannot protect against lyssaviruses from phylogroup II. Our tree
      axial analysis divided lyssaviruses into two phylogroups that more closely
      reflect their biological characteristics than previous serotypes and genotypes.

PMID- 11238854
TI  - Epitope mapping porcine reproductive and respiratory syndrome virus by phage
      display: the nsp2 fragment of the replicase polyprotein contains a cluster of B
      cell epitopes.
AB  - We screened phage display libraries of porcine reproductive and respiratory
      syndrome virus (PRRSV) protein fragments with sera from experimentally infected
      pigs to identify linear B-cell epitopes that are commonly recognized during
      infection in vivo. We identified 10 linear epitope sites (ES) 11 to 53 amino
      acids in length. In the replicase polyprotein, a total of eight ES were
      identified, six of which localized to the Nsp2 replicase polyprotein processing
      end product. In the structural proteins, a total of two ES were identified, in
      the ORF3 and ORF4 minor envelope glycoproteins. The ORF4 ES was previously
      identified by monoclonal antibody mapping (J. J. M. Meulenberg, A. P. van
      Nieuwstadt, A. van Essen-Zandenbergen, and J. P. M. Langeveld, J. Virol. 71:6061
      6067, 1997), but its immunogenicity had not been examined in pigs. We found that
      six experimentally PRRSV-infected pigs consistently had very high antibody titers
      against the ORF4 ES. In some animals, sera diluted 1:62,500 still gave weak
      positive enzyme immunoassay reactivity against the ORF4 ES. This hitherto
      unrecognized immunodominance likely caused phages displaying the ORF4 ES to
      outcompete phages displaying other ES during library screening with porcine sera
      and accounted for our failure to identify more than two ES in the structural
      genes of PRRSV. Genetic analysis showed that variable ES were also the most
      immunogenic in vivo. Serological analysis indicated differences in the
      immunoglobulin A responses between short-term and longer-term viremic pigs
      towards some ES. The implications of these findings for PRRSV diagnostics and
      immunopathogenesis are discussed.

PMID- 11238855
TI  - Individual contributions of mutant protease and reverse transcriptase to viral
      infectivity, replication, and protein maturation of antiretroviral drug-resistant
      human immunodeficiency virus type 1.
AB  - Human immunodeficiency virus type 1 (HIV-1) variants resistant to protease (PR)
      and reverse transcriptase (RT) inhibitors may display impaired infectivity and
      replication capacity. The individual contributions of mutated HIV-1 PR and RT to
      infectivity, replication, RT activity, and protein maturation (herein referred to
      as "fitness") in recombinant viruses were investigated by separately cloning PR,
      RT, and PR-RT cassettes from drug-resistant mutant viral isolates into the wild
      type NL4-3 background. Both mutant PR and RT contributed to measurable deficits
      in fitness of viral constructs. In peripheral blood mononuclear cells,
      replication rates (means +/- standard deviations) of RT recombinants were 72.5%
      +/- 27.3% and replication rates of PR recombinants were 60.5% +/- 33.6% of the
      rates of NL4-3. PR mutant deficits were enhanced in CEM T cells, with relative
      replication rates of PR recombinants decreasing to 15.8% +/- 23.5% of NL4-3
      replication rates. Cloning of the cognate RT improved fitness of some PR mutant
      clones. For a multidrug-resistant virus transmitted through sexual contact, RT
      constructs displayed a marked infectivity and replication deficit and diminished
      packaging of Pol proteins (RT content in virions diminished by 56.3% +/- 10.7%,
      and integrase content diminished by 23.3% +/- 18.4%), a novel mechanism for a
      decreased-fitness phenotype. Despite the identified impairment of recombinant
      clones, fitness of two of the three drug-resistant isolates was comparable to
      that of wild-type, susceptible viruses, suggestive of extensive compensation by
      genomic regions away from PR and RT. Only limited reversion of mutated positions
      to wild-type amino acids was observed for the native isolates over 100 viral
      replication cycles in the absence of drug selective pressure. These data
      underscore the complex relationship between PR and RT adaptive changes and viral
      evolution in antiretroviral drug-resistant HIV-1.

PMID- 11238856
TI  - Human immunodeficiency virus type 1 central DNA flap: dynamic terminal product of
      plus-strand displacement dna synthesis catalyzed by reverse transcriptase
      assisted by nucleocapsid protein.
AB  - To terminate the reverse transcription of the human immunodeficiency virus type 1
      (HIV-1) genome, a final step occurs within the center of the proviral DNA
      generating a 99-nucleotide DNA flap (6). This step, catalyzed by reverse
      transcriptase (RT), is defined as a discrete strand displacement (SD) synthesis
      between the first nucleotide after the central priming (cPPT) site and the final
      position of the central termination sequence (CTS) site. Using recombinant HIV-1
      RT and a circular single-stranded DNA template harboring the cPPT-CTS sequence,
      we have developed an SD synthesis-directed in vitro termination assay.
      Elongation, strand displacement, and complete central flap behavior were analyzed
      using electrophoresis and electron microscopy approaches. Optimal conditions to
      obtain complete central flap, which ended at the CTS site, have been defined in
      using nucleocapsid protein (NCp), the main accessory protein of the reverse
      transcription complex. A full-length HIV-1 central DNA flap was then carried out
      in vitro. Its synthesis appears faster in the presence of the HIV-1 NCp or the T4
      encoded SSB protein (gp32). Finally, a high frequency of strand transfer was
      shown during the SD synthesis along the cPPT-CTS site with RT alone. This reveals
      a local and efficient 3'-5' branch migration which emphasizes some important
      structural fluctuations within the flap. These fluctuations may be stabilized by
      the NCp chaperone activity. The biological implications of the RT-directed NCp
      assisted flap synthesis are discussed within the context of reverse transcription
      complexes, assembly of the preintegration complexes, and nuclear import of the
      HIV-1 proviral DNA to the nucleus toward their chromatin targets.

PMID- 11238857
TI  - Tissue-specific, tumor-selective, replication-competent adenovirus vector for
      cancer gene therapy.
AB  - We have previously described two replication-competent adenovirus vectors, named
      KD1 and KD3, for potential use in cancer gene therapy. KD1 and KD3 have two small
      deletions in the E1A gene that restrict efficient replication of these vectors to
      human cancer cell lines. These vectors also have increased capacity to lyse cells
      and spread from cell to cell because they overexpress the adenovirus death
      protein, an adenovirus protein required for efficient cell lysis and release of
      adenovirus from the cell. We now describe a new vector, named KD1-SPB, which is
      the KD1 vector with the E4 promoter replaced by the promoter for surfactant
      protein B (SPB). SPB promoter activity is restricted in the adult to type II
      alveolar epithelial cells and bronchial epithelial cells. Because KD1-SPB has the
      E1A mutations, it should replicate within and destroy only alveolar and bronchial
      cancer cells. We show that KD1-SPB replicates, lyses cells, and spreads from cell
      to cell as well as does KD1 in H441 cells, a human cancer cell line where the SPB
      promoter is active. KD1-SPB replicates, lyses cells, and spreads only poorly in
      Hep3B liver cancer cells. Replication was determined by expression of the E4ORF3
      protein, viral DNA accumulation, fiber synthesis, and virus yield. Cell lysis and
      vector spread were measured by lactate dehydrogenase release and a "vector
      spread" assay. In addition to Hep3B cells, KD1-SPB also did not express E4ORF3 in
      HT29.14S (colon), HeLa (cervix), KB (nasopharynx), or LNCaP (prostate) cancer
      cell lines, in which the SPB promoter is not expected to be active. Following
      injection into H441 or Hep3B tumors growing in nude mice, KD1-SPB caused a three-
      to fourfold suppression of growth of H441 tumors, similar to that seen with KD1.
      KD1-SPB had only a minimal effect on the growth of Hep3B tumors, whereas KD1
      again caused a three- to fourfold suppression. These results establish that the
      adenovirus E4 promoter can be replaced by a tissue-specific promoter in a
      replication-competent vector. The vector has three engineered safety features:
      the tissue-specific promoter, the mutations in E1A that preclude efficient
      replication in nondividing cells, and a deletion of the E3 genes which shield the
      virus from attack by the immune system. KD1-SPB may have use in treating human
      lung cancers in which the SPB promoter is active.

PMID- 11238858
TI  - Detection of direct binding of human herpesvirus 8-encoded interleukin-6 (vIL-6)
      to both gp130 and IL-6 receptor (IL-6R) and identification of amino acid residues
      of vIL-6 important for IL-6R-dependent and -independent signaling.
AB  - Human herpesvirus 8 (HHV-8) is associated with Kaposi's sarcoma, primary effusion
      lymphoma, and multicentric Castleman's disease; in all of these diseases,
      interleukin-6 (IL-6) has been implicated as a likely mitogenic and/or angiogenic
      factor. HHV-8 encodes a homologue of IL-6 (viral IL-6 [vIL-6]) that has been
      shown to be biologically active in several assays and whose activities mirror
      those of its mammalian counterparts. Like these proteins, vIL-6 mediates its
      effects through the gp130 signal transducer, but signaling is not dependent on
      the structurally related IL-6 receptor (IL-6R; gp80) subunit of the receptor
      signal transducer complex. However, as we have shown previously, IL-6R can
      enhance vIL-6 signal transduction and can enable signaling through a gp130
      variant (gp130.PM5) that is itself unable to support vIL-6 activity, indicating
      that IL-6R can form part of the signaling complex. Also, our analysis of a panel
      of vIL-6 mutants in transfection experiments in Hep3B cells (that express IL-6R
      and gp130) showed that most were able to function normally in this system. Here,
      we have used in vitro vIL-6-receptor binding assays to demonstrate direct binding
      of vIL-6 to both gp130 and IL-6R and vIL-6-induced gp130-IL-6R complex formation,
      and we have extended our functional analyses of the vIL-6 variants to identify
      residues important for IL-6R-independent and IL-6R-dependent signaling through
      native gp130 and gp130.PM5, respectively. These studies have identified residues
      in vIL-6 that are important for IL-6R-independent and IL-6R-mediated functional
      complex formation between vIL-6 and gp130 and that may be involved directly in
      binding to gp130 and IL-6R.

PMID- 11238859
TI  - Improved adenovirus vectors for infection of cardiovascular tissues.
AB  - To identify improved adenovirus vectors for cardiovascular gene therapy, a
      library of adenovirus vectors based on adenovirus serotype 5 (Ad5) but carrying
      fiber molecules of other human serotypes, was generated. This library was tested
      for efficiency of infection of human primary vascular endothelial cells (ECs) and
      smooth muscle cells (SMCs). Based on luciferase, LacZ, or green fluorescent
      protein (GFP) marker gene expression, several fiber chimeric vectors were
      identified that displayed improved infection of these cell types. One of the
      viruses that performed particularly well is an Ad5 carrying the fiber of Ad16
      (Ad5.Fib16), a subgroup B virus. This virus showed, on average, 8- and 64-fold
      increased luciferase activities on umbilical vein ECs and SMCs, respectively,
      compared to the parent vector. GFP and lacZ markers showed that approximately 3
      fold (ECs) and 10-fold (SMCs) more cells were transduced. Experiments performed
      with both cultured SMCs and organ cultures derived from different vascular
      origins (saphenous vein, iliac artery, left interior mammary artery, and aorta)
      and from different species demonstrated that Ad5.Fib16 consistently displays
      improved infection in primates (humans and rhesus monkeys). SMCs of the same
      vessels of rodents and pigs were less infectable with Ad5.Fib16 than with Ad5.
      This suggests that either the receptor for human Ad16 is not conserved between
      different species or that differences in the expression levels of the putative
      receptor exist. In conclusion, our results show that an Ad5-based virus carrying
      the fiber of Ad16 is a potent vector for the transduction of primate
      cardiovascular cells and tissues.

PMID- 11238860
TI  - Roles of macrophages in measles virus infection of genetically modified mice.
AB  - Knowledge of the mechanisms of virus dissemination in acute measles is cursory,
      but cells of the monocyte/macrophage (MM) lineage appear to be early targets. We
      characterized the dissemination of the Edmonston B vaccine strain of measles
      virus (MV-Ed) in peripheral blood mononuclear cells (PBMC) of two mouse strains
      expressing the human MV-Ed receptor CD46 with human-like tissue specificity and
      efficiency. In one strain the alpha/beta interferon receptor is defective,
      allowing for efficient MV-Ed systemic spread. In both mouse strains the PBMC most
      efficiently infected were F4/80-positive MMs, regardless of the inoculation route
      used. Circulating B lymphocytes and CD4-positive T lymphocytes were infected at
      lower levels, but no infected CD8-positive T lymphocytes were detected. To
      elucidate the roles of MMs in infection, we depleted these cells by clodronate
      liposome treatment in vivo. MV-Ed infection of splenic MM-depleted mice caused
      strong activation and infection of splenic dendritic cells (DC), followed by
      enhanced virus replication in the spleen. Similarly, depletion of lung
      macrophages resulted in strong activation and infection of lung DC. Thus, in MV
      infections of genetically modified mice, blood monocytes and tissue macrophages
      provide functions beneficial for both the virus and the host: they support virus
      replication early after infection, but they also contribute to protecting other
      immune cells from infection. Human MM may have similar roles in acute measles.

PMID- 11238861
TI  - Mitochondrial aconitase binds to the 3' untranslated region of the mouse
      hepatitis virus genome.
AB  - Mouse hepatitis virus (MHV), a member of the Coronaviridae, contains a
      polyadenylated positive-sense single-stranded genomic RNA which is 31 kb long.
      MHV replication and transcription take place via the synthesis of negative-strand
      RNA intermediates from a positive-strand genomic template. A cis-acting element
      previously identified in the 3' untranslated region binds to trans-acting host
      factors from mouse fibroblasts and forms at least three RNA-protein complexes.
      The largest RNA-protein complex formed by the cis-acting element and the lysate
      from uninfected mouse fibroblasts has a molecular weight of about 200 kDa. The
      complex observed in gel shift assays has been resolved by second-dimension sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis into four proteins of
      approximately 90, 70, 58, and 40 kDa after RNase treatment. Specific RNA affinity
      chromatography also has revealed the presence of a 90-kDa protein associated with
      RNA containing the cis-acting element bound to magnetic beads. The 90-kDa protein
      has been purified from uninfected mouse fibroblast crude lysates. Protein
      microsequencing identified the 90-kDa protein as mitochondrial aconitase.
      Antibody raised against purified mitochondrial aconitase recognizes the RNA
      protein complex and the 90-kDa protein, which can be released from the complex by
      RNase digestion. Furthermore, UV cross-linking studies indicate that highly
      purified mitochondrial aconitase binds specifically to the MHV 3' protein-binding
      element. Increasing the intracellular level of mitochondrial aconitase by iron
      supplementation resulted in increased RNA-binding activity in cell extracts and
      increased virus production as well as viral protein synthesis at early hours of
      infection. These results are particularly interesting in terms of identification
      of an RNA target for mitochondrial aconitase, which has a cytoplasmic homolog,
      cytoplasmic aconitase, also known as iron regulatory protein 1, a well-recognized
      RNA-binding protein. The binding properties of mitochondrial aconitase and the
      functional relevance of RNA binding appear to parallel those of cytoplasmic
      aconitase.

PMID- 11238862
TI  - Single amino acid substitution in the V protein of simian virus 5 differentiates
      its ability to block interferon signaling in human and murine cells.
AB  - Previous work has demonstrated that the V protein of simian virus 5 (SV5) targets
      STAT1 for proteasome-mediated degradation (thereby blocking interferon [IFN]
      signaling) in human but not in murine cells. In murine BF cells, SV5 establishes
      a low-grade persistent infection in which the virus fluxes between active and
      repressed states in response to local production of IFN. Upon passage of
      persistently infected BF cells, virus mutants were selected that were better able
      to replicate in murine cells than the parental W3 strain of SV5 (wild type [wt]).
      Viruses with mutations in the Pk region of the N-terminal domain of the V protein
      came to predominate the population of viruses carried in the persistently
      infected cell cultures. One of these mutant viruses, termed SV5 mci-2, was
      isolated. Sequence analysis of the V/P gene of SV5 mci-2 revealed two nucleotide
      differences compared to wt SV5, only one of which resulted in an amino acid
      substitution (asparagine [N], residue 100, to aspartic acid [D]) in V. Unlike the
      protein of wt SV5, the V protein of SV5 mci-2 blocked IFN signaling in murine
      cells. Since the SV5 mci-2 virus had additional mutations in genes other than the
      V/P gene, a recombinant virus (termed rSV5-V/P N(100)D) was constructed that
      contained this substitution alone within the wt SV5 backbone to evaluate what
      effect the asparagine-to-aspartic-acid substitution in V had on the virus
      phenotype. In contrast to wt SV5, rSV5-V/P N(100)D blocked IFN signaling in
      murine cells. Furthermore, rSV5-V/P N(100)D virus protein synthesis in BF cells
      continued for significantly longer periods than that for wt SV5. However, even in
      cells infected with rSV5-V/P N(100)D, there was a late, but significant,
      inhibition in virus protein synthesis. Nevertheless, there was an increase in
      virus yield from BF cells infected with rSV5-V/P N(100)D compared to wt SV5,
      demonstrating a clear selective advantage to SV5 in being able to block IFN
      signaling in these cells.

PMID- 11238863
TI  - Construction and molecular analysis of gene transfer systems derived from bovine
      immunodeficiency virus.
AB  - Because lentiviruses are able to infect nondividing cells, these viruses might be
      utilized in gene therapy applications where the target cell does not divide.
      However, it has been suggested that the introduction of primate lentivirus
      sequences, particularly those of human immunodeficiency virus, into human cells
      may pose a health risk for the patient. To avoid this concern, we have
      constructed gene transfer systems based on a nonprimate lentivirus, bovine
      immunodeficiency virus. A panel of vectors and packaging constructs was generated
      and analyzed in a transient expression system for virion production and
      maturation, vector expression and encapsidation, and envelope protein
      pseudotyping. Virion preparations were also analyzed for transduction efficiency
      in a panel of human and nonhuman primary cells and immortalized cell lines. The
      virion preparations transduced most of the target cell types, with efficiencies
      up to 90% and with titers of unconcentrated virus up to 5 x 10(5) infectious
      doses/ml. In addition, infection of nondividing human cells, including
      unstimulated hematopoietic stem cells and irradiated endothelial cells, was
      observed.

PMID- 11238864
TI  - Viral regulation of RANTES expression during human cytomegalovirus infection of
      endothelial cells.
AB  - Human cytomegalovirus (HCMV) evades healthy immune responses during infection,
      and this evasion may allow HCMV to establish latency in the host. The human
      vasculature has been recognized as a site of HCMV infection and may also be a
      site of latent HCMV infection. As the interface between circulating cells and
      underlying parenchymal cells, the vascular endothelium provides signals for local
      reaction of inflammatory cells. We propose that HCMV down-regulates expression of
      the proinflammatory chemokine RANTES from the infected endothelium, which may
      result in reduced recruitment of mononuclear cells to the site of infection.
      Abortive HCMV infection of primary endothelial cells with the clinical isolate
      HCMV 4010, under conditions in which viral gene expression could not occur,
      induced high levels of RANTES expression. Replicative HCMV infection, however,
      induced cells in parallel cultures to express significantly lower levels of
      RANTES. Expression of the chemokines interleukin 8 and MCP-1 by endothelial cells
      was found to be unaffected by replicative HCMV infection and thus may not play an
      important role during early HCMV infection of the endothelium. HCMV may regulate
      RANTES expression from endothelial cells as a mechanism to evade the local immune
      response to infection.

PMID- 11238865
TI  - Efficient activation of viral genomes by levels of herpes simplex virus ICP0
      insufficient to affect cellular gene expression or cell survival.
AB  - Herpes simplex virus (HSV) ICP0 can effectively activate gene expression from
      otherwise silent promoters contained on persisting viral genomes. However, the
      expression of high levels of ICP0, as from ICP4(-) HSV type 1 (HSV-1) vectors,
      results in marked toxicity. We have analyzed the results of ICP0 expressed from
      an E1(-) E4(-) adenovirus vector (AdS.11E4ICP0) in which ICP0 expression is
      controlled from the endogenous adenoviral E4 promoter. In this system, the
      expression level of ICP0 was reduced more than 1,000-fold relative to the level
      of expression from HSV-1 vectors. This low level of ICP0 did not affect cellular
      division or greatly perturb cellular metabolism as assessed by gene expression
      array analysis comparing the effects of HSV and adenovirus vector strains.
      However, this amount of ICP0 was sufficient to quantitatively destroy ND10
      structures as measured by promyelocytic leukemia immunofluorescence. The levels
      of adenovirus-expressed ICP0 were sufficient to activate quiescent viral genomes
      in trans and promote persistent transgene expression in cis. Moreover, infection
      of complementing cells with AdS.11E4ICP0 promoted viral growth and resulted in a
      20-fold increase in the plaquing efficiency of d109, a virus defective for all
      five immediate-early genes. Thus, the low level expression of ICP0 from the E1(-)
      E4(-) adenovirus vector may increase the utility of adenovirus vectors and also
      provides a means to efficiently quantify and possibly propagate HSV vectors
      defective in ICP0. Importantly, the results demonstrate that the activation
      function of ICP0 may not result from changes in cellular gene expression, but
      possibly as a direct consequence of an enzymatic function inherent to the protein
      that may involve its action at ND10 resulting in the preferential activation of
      viral genomes.

PMID- 11238866
TI  - Borna disease virus nucleoprotein requires both nuclear localization and export
      activities for viral nucleocytoplasmic shuttling.
AB  - Nuclear transport of viral nucleic acids is crucial to the life cycle of many
      viruses. Borna disease virus (BDV) belongs to the order Mononegavirales and
      replicates its RNA genome in the nucleus. Previous studies have suggested that
      BDV nucleoprotein (N) and phosphoprotein (P) have important functions in the
      nuclear import of the viral ribonucleoprotein (RNP) complexes via their nuclear
      targeting activity. Here, we showed that BDV N has cytoplasmic localization
      activity, which is mediated by a nuclear export signal (NES) within the sequence.
      Our analysis using deletion and substitution mutants of N revealed that NES of
      BDV N consists of a canonical leucine-rich motif and that the nuclear export
      activity of the protein is mediated through the chromosome region maintenance
      protein-dependent pathway. Interspecies heterokaryon assay indicated that BDV N
      shuttles between the nucleus and cytoplasm as a nucleocytoplasmic shuttling
      protein. Furthermore, interestingly, the NES region overlaps a binding site to
      the BDV P protein, and nuclear export of a 38-kDa form of BDV N is prevented by
      coexpression of P. These results suggested that BDV N has two contrary
      activities, nuclear localization and export activity, and plays a critical role
      in the nucleocytoplasmic transport of BDV RNP by interaction with other viral
      proteins.

PMID- 11238867
TI  - Analysis of protein expression from within the region encoding the 2.0-kilobase
      latency-associated transcript of herpes simplex virus type 1.
AB  - During latent infections of sensory neurons, herpes simplex virus type 1 gene
      expression is restricted to the latency-associated transcripts (LATs). The
      association of the stable 2.0-kb LAT intron with polysomes has suggested that it
      might represent a novel mRNA. In this work, we investigated expression of 2.0-kb
      LAT open reading frames (ORFs) by inserting the gene for green fluorescent
      protein (GFP) within the 2.0-kb LAT sequence, both within a LAT expression
      plasmid and in the context of the virus. Upon transient transfection of cells of
      both neuronal and nonneuronal origin with LAT-GFP expression vectors, low-level
      GFP fluorescence was distributed over the cell cytoplasm and likely resulted from
      infrequent initiation at a GFP AUG codon, on either unspliced or alternately
      spliced LAT RNAs. A second nucleolar GFP expression pattern which resulted from
      fusion of GFP to a conserved ORF in exon 1 of the LAT gene was also observed.
      However, the abundant expression of this fusion protein was dependent upon an
      artificially added translation initiation codon. Expression was much reduced and
      restricted to a small subset of transfected cells when this initiator codon was
      removed. Neither the 2.0-kb LAT-GFP intron itself nor transcripts originating
      from the latency-associated promoter 2 (LAP2) were responsible for GFP
      expression. Abundant alternate splicing involving the 1.5-kb LAT splice acceptor
      and including splicing between the 1.5-kb LAT splice donor and acceptor, was
      observed in the nonneuronal Cos-1 cell line. Contrary to the results of our
      transfection studies, GFP expression could not be detected from a LAT-GFP virus
      at any stage of the infection cycle. Our results suggest that the inhibition of
      LAT ORF expression during viral infection occurred primarily at the level of
      translation.

PMID- 11238868
TI  - Rabies virus ocular disease: T-cell-dependent protection is under the control of
      signaling by the p55 tumor necrosis factor alpha receptor, p55TNFR.
AB  - Following brain infection, the Challenge Virus Standard strain of rabies virus
      infects the retina. Rabies virus ocular infection induces the infiltration of
      neutrophils and predominantly T cells into the eye. The role of tumor necrosis
      factor alpha (TNF-alpha)-lymphotoxin signaling in the control of rabies virus
      ocular infection and inflammatory cell infiltration was assessed using mice
      lacking the p55 TNF-alpha receptor (p55TNFR(-/-) mice). The incidence of ocular
      disease and the intensity of retinal infection were greater in p55TNFR(-/-) mice
      than in C57BL/6 mice: the aggravation correlated with less neutrophil and T-cell
      infiltration. This indicates that cellular infiltration is under the control of
      the p55 TNF-alpha receptor and suggests that inflammatory cells may protect the
      eye against rabies virus ocular infection. The role of T cells following rabies
      virus ocular disease was assessed by comparison of rabies virus infection in nude
      mice with their normal counterparts. Indeed, the incidence and severity of the
      rabies virus ocular disease were higher in athymic nude mice than in BALB/c mice,
      indicating that T lymphocytes are protective during rabies virus ocular
      infection. Moreover, few T cells and neutrophils underwent apoptosis in rabies
      virus-infected retina. Altogether, these data suggest that T lymphocytes and
      neutrophils are able to enter the eye, escape the immune privilege status, and
      limit rabies virus ocular disease. In conclusion, rabies virus-mediated eye
      disease provides a new model for studying mechanisms regulating immune privilege
      during viral infection.

PMID- 11238869
TI  - Loss of a single N-linked glycan allows CD4-independent human immunodeficiency
      virus type 1 infection by altering the position of the gp120 V1/V2 variable
      loops.
AB  - The gp120 envelope glycoprotein of primary human immunodeficiency virus type 1
      (HIV-1) promotes virus entry by sequentially binding CD4 and the CCR5 chemokine
      receptor on the target cell. Previously, we adapted a primary HIV-1 isolate, ADA,
      to replicate in CD4-negative canine cells expressing human CCR5. The gp120
      changes responsible for CD4-independent replication were limited to the V2 loop
      V1/V2 stem. Here we show that elimination of a single glycosylation site at
      asparagine 197 in the V1/V2 stem is sufficient for CD4-independent gp120 binding
      to CCR5 and for HIV-1 entry into CD4-negative cells expressing CCR5. Deletion of
      the V1/V2 loops also allowed CD4-independent viral entry and gp120 binding to
      CCR5. The binding of the wild-type ADA gp120 to CCR5 was less dependent upon CD4
      at 4 degrees C than at 37 degrees C. In the absence of the V1/V2 loops, neither
      removal of the N-linked carbohydrate at asparagine 197 nor lowering of the
      temperature increased the CD4-independent phenotypes. A CCR5-binding conformation
      of gp120, achieved by CD4 interaction or by modification of temperature,
      glycosylation, or variable loops, was preferentially recognized by the monoclonal
      antibody 48d. These results suggest that the CCR5-binding region of gp120 is
      occluded by the V1/V2 variable loops, the position of which can be modulated by
      temperature, CD4 binding, or an N-linked glycan in the V1/V2 stem.

PMID- 11238870
TI  - Inhibition of histone deacetylation induces constitutive derepression of the beta
      interferon promoter and confers antiviral activity.
AB  - The induction of alpha/beta interferon (IFN-alpha/beta) genes constitutes one of
      the first responses of the cell to virus infection. The IFN-beta gene is
      constitutively repressed in uninfected cells and is transiently activated after
      virus infection. In this work we demonstrate that histone deacetylation regulates
      the silent state of the murine IFN-beta gene. Using chromatin immunoprecipitation
      (ChIP) assays, we show a direct in vivo correlation between the transcriptionally
      silent state and a state of hypoacetylation of histone H4 on the IFN-beta
      promoter region. Trichostatin A (TSA), a specific inhibitor of histone
      deacetylases, induced strong, constitutive derepression of the murine IFN-beta
      promoter stably integrated into a chromatin context, as well as the
      hyperacetylation of histone H4, without requiring de novo protein synthesis. We
      also show in this work that TSA treatment strongly enhances the endogenous IFN
      level and confers an antiviral state to murine fibroblastic L929 cells.
      Inhibition of histone deacetylation with TSA protected the cells against the lost
      of viability induced by vesicular stomatitis virus (VSV) and inhibited VSV
      multiplication. Using antibodies neutralizing IFN-alpha/beta, we show that the
      antiviral state induced by TSA is due to TSA-induced IFN production. The
      demonstration of the predominant role of histone deacetylation during the
      regulation of the constitutive repressed state of the IFN-beta promoter
      constitutes an interesting advance on the understanding of the negative
      regulation of this gene and opens up the possibility of new therapeutic
      perspectives.

PMID- 11238871
TI  - Branched polyamines cure prion-infected neuroblastoma cells.
AB  - Branched polyamines, including polyamidoamine and polypropyleneimine (PPI)
      dendrimers, are able to purge PrP(Sc), the disease-causing isoform of the prion
      protein, from scrapie-infected neuroblastoma (ScN2a) cells in culture (S.
      Supattapone, H.-O. B. Nguyen, F. E. Cohen, S. B. Prusiner, and M. R. Scott, Proc.
      Natl. Acad. Sci. USA 96:14529-14534, 1999). We now demonstrate that exposure of
      ScN2a cells to 3 microg of PPI generation 4.0/ml for 4 weeks not only reduced
      PrP(Sc) to a level undetectable by Western blot but also eradicated prion
      infectivity as determined by a bioassay in mice. Exposure of purified RML prions
      to branched polyamines in vitro disaggregated the prion rods, reduced the beta
      sheet content of PrP 27-30, and rendered PrP 27-30 susceptible to proteolysis.
      The susceptibility of PrP(Sc) to proteolytic digestion induced by branched
      polyamines in vitro was strain dependent. Notably, PrP(Sc) from bovine spongiform
      encephalopathy-infected brain was susceptible to PPI-mediated denaturation in
      vitro, whereas PrP(Sc) from natural sheep scrapie-infected brain was resistant.
      Fluorescein-labeled PPI accumulated specifically in lysosomes, suggesting that
      branched polyamines act within this acidic compartment to mediate PrP(Sc)
      clearance. Branched polyamines are the first class of compounds shown to cure
      prion infection in living cells and may prove useful as therapeutic,
      disinfecting, and strain-typing reagents for prion diseases.

PMID- 11238872
TI  - Naturally occurring deletional mutation in the C-terminal cytoplasmic tail of
      CCR5 affects surface trafficking of CCR5.
AB  - CCR5 is an essential coreceptor for the cellular entry of R5 strains of human
      immunodeficiency virus type 1 (HIV-1). CCR5-893(-) is a single-nucleotide
      deletion mutation which is observed exclusively in Asians (M. A. Ansari-Lari, et
      al., Nat. Genet. 16:221-222, 1997). This mutant gene produces a CCR5 which lacks
      the entire C-terminal cytoplasmic tail. To assess the effect of CCR5-893(-) on
      HIV-1 infection, we generated a recombinant Sendai virus expressing the mutant
      CCR5 and compared its HIV-1 coreceptor activity with that of wild-type CCR5.
      Although the mutant CCR5 has intact extracellular domains, its coreceptor
      activity was much less than that of wild-type CCR5. Flow cytometric analyses and
      confocal microscopic observation of cells expressing the mutant CCR5 revealed
      that surface CCR5 levels were greatly reduced in these cells, while cytoplasmic
      CCR5 levels of the mutant CCR5 were comparable to that of the wild type.
      Peripheral blood CD4(+) T cells obtained from individuals heterozygous for this
      allele expressed very low levels of CCR5. These data suggest that the CCR5-893(-)
      mutation affects intracellular transport of CCR5 and raise the possibility that
      this mutation also affects HIV-1 transmission and disease progression.

PMID- 11238873
TI  - Replication of the human hepatitis delta virus genome Is initiated in mouse
      hepatocytes following intravenous injection of naked DNA or RNA sequences.
AB  - As early as 5 days after DNA copies of the hepatitis delta virus (HDV) genome or
      even in vitro-transcribed HDV RNA sequences were injected into the mouse tail
      vein using the hydrodynamics-based transfection procedure of F. Liu et al. (Gene
      Ther. 6:1258-1266, 1999), it was possible to detect in the liver by Northern
      analyses of RNA, immunoblots of protein, and immunostaining of liver sections
      what were considered typical features of HDV genome replication. This
      transfection strategy should have valuable applications for in vivo studies of
      HDV replication and pathogenesis and may also be useful for studies of other
      hepatotropic viruses.

PMID- 11238875
TI  - Regression of a murine gammaherpesvirus 68-positive b-cell lymphoma mediated by
      CD4 T lymphocytes.
AB  - Murine gammaherpesvirus 68-infected S11 cells were injected subcutaneously into
      nude mice. Adoptively transferred restimulated lymphocytes consistently elicited
      the regression of S11 tumors. CD4 T lymphocytes were most effective in preventing
      tumor formation, and immunohistochemistry highlighted populations of CD4 T cells
      in regressing tumors.

PMID- 11238874
TI  - Oncolytic activity of vesicular stomatitis virus is effective against tumors
      exhibiting aberrant p53, Ras, or myc function and involves the induction of
      apoptosis.
AB  - We have recently shown that vesicular stomatitis virus (VSV) exhibits potent
      oncolytic activity both in vitro and in vivo (S. Balachandran and G. N. Barber,
      IUBMB Life 50:135-138, 2000). In this study, we further demonstrated, in vivo,
      the efficacy of VSV antitumor action by showing that tumors that are defective in
      p53 function or transformed with myc or activated ras are also susceptible to
      viral cytolysis. The mechanism of viral oncolytic activity involved the induction
      of multiple caspase-dependent apoptotic pathways was effective in the absence of
      any significant cytotoxic T-lymphocyte response, and occurred despite normal PKR
      activity and eIF2alpha phosphorylation. In addition, VSV caused significant
      inhibition of tumor growth when administered intravenously in immunocompetent
      hosts. Our data indicate that VSV shows significant promise as an effective
      oncolytic agent against a wide variety of malignant diseases that harbor a
      diversity of genetic defects.

PMID- 11238876
TI  - JC virus-specific cytotoxic T lymphocytes in individuals with progressive
      multifocal leukoencephalopathy.
AB  - Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of
      the central nervous system caused by a reactivation of the polyomavirus JC (JCV)
      within a setting of immunosuppression. The nature of the immune response that
      contains replication of this virus is unknown. We have explored JCV-specific
      cellular immune responses in patients with PML and control subjects. JCV antigen
      stimulated peripheral blood mononuclear cells (PBMC) of four human
      immunodeficiency virus (HIV)-infected patients who were survivors of PML and one
      HIV-uninfected patient recently diagnosed with PML lysed autologous B
      lymphoblastoid cell lines expressing either the JCV T regulatory protein or the
      VP1 major capsid protein. This lysis was mediated by CD8(+) T lymphocytes and was
      major histocompatibility complex class I restricted. These cells were therefore
      cytotoxic T lymphocytes (CTL). JCV-specific CTL could not be detected in PBMC of
      three HIV-infected PML patients who had progressive neurologic disease and an
      eventual fatal outcome. These data suggest that the JCV-specific cellular immune
      response may play a crucial role in the containment of PML. This finding may also
      prove useful as a favorable prognostic marker in the clinical management of these
      patients.

PMID- 11238877
TI  - Envelope gene of the human endogenous retrovirus HERV-W encodes a functional
      retrovirus envelope.
AB  - A member of the human endogenous retrovirus (HERV) family termed HERV-W encodes a
      highly fusogenic membrane glycoprotein that appears to be expressed specifically
      in the placenta. It is unclear whether the glycoproteins of the HERVs can serve
      as functional retrovirus envelope proteins to confer infectivity on retrovirus
      particles. We found that the HERV-W envelope glycoprotein can form pseudotypes
      with human immunodeficiency virus type 1 virions and confers tropism for CD4
      negative cells. Thus, the HERV-W env gene represents the first HERV env gene
      demonstrated to encode the functional properties of a retrovirus envelope
      glycoprotein.

PMID- 11238878
TI  - Imported parakeets harbor H9N2 influenza A viruses that are genetically closely
      related to those transmitted to humans in Hong Kong.
AB  - In 1997 and 1998, H9N2 influenza A viruses were isolated from the respiratory
      organs of Indian ring-necked parakeets (Psittacula Krameri manillensis) that had
      been imported from Pakistan to Japan. The two isolates were closely related to
      each other (>99% as determined by nucleotide analysis of eight RNA segments),
      indicating that H9N2 viruses of the same lineage were maintained in these birds
      for at least 1 year. The hemagglutinins and neuraminidases of both isolates
      showed >97% nucleotide identity with those of H9N2 viruses isolated from humans
      in Hong Kong in 1999, while the six genes encoding internal proteins were >99%
      identical to the corresponding genes of H5N1 viruses recovered during the 1997
      outbreak in Hong Kong. These results suggest that the H9N2 parakeet viruses
      originating in Pakistan share an immediate ancestor with the H9N2 human viruses.
      Thus, influenza A viruses with the potential to be transmitted directly to humans
      may be circulating in captive birds worldwide.

PMID- 11238879
TI  - Repair of a Rev-minus human immunodeficiency virus type 1 mutant by activation of
      a cryptic splice site.
AB  - We isolated a revertant virus after prolonged culturing of a replication-impaired
      human immunodeficiency virus type 1 (HIV-1) mutant of which the Rev open reading
      frame was inactivated by mutation of the AUG translation initiation codon.
      Sequencing of the tat-rev region of this revertant virus identified a second-site
      mutation in tat that restored virus replication in the mutant background. This
      mutation activated a cryptic 5' splice site (ss) that, when used in conjunction
      with the regular HIV 3' ss #5, fuses the tat and rev reading frames to encode a
      novel T-Rev fusion protein that rescues Rev function. We also demonstrate an
      alternative route to indirectly activate this cryptic 5' ss by mutational
      inactivation of an adjacent exon splicing silencer element.

PMID- 11238880
TI  - A Ras by any other name.

PMID- 11238881
TI  - Targeted genomic disruption of H-ras and N-ras, individually or in combination,
      reveals the dispensability of both loci for mouse growth and development.
AB  - Mammalian cells harbor three highly homologous and widely expressed members of
      the ras family (H-ras, N-ras, and K-ras), but it remains unclear whether they
      play specific or overlapping cellular roles. To gain insight into such functional
      roles, here we generated and analyzed H-ras null mutant mice, which were then
      also bred with N-ras knockout animals to ascertain the viability and properties
      of potential double null mutations in both loci. Mating among heterozygous H
      ras(+/-) mice produced H-ras(-/-) offspring with a normal Mendelian pattern of
      inheritance, indicating that the loss of H-ras did not interfere with embryonic
      and fetal viability in the uterus. Homozygous mutant H-ras(-/-) mice reached
      sexual maturity at the same age as their littermates, and both males and females
      were fertile. Characterization of lymphocyte subsets in the spleen and thymus
      showed no significant differences between wild-type and H-ras(-/-) mice. Analysis
      of neuronal markers in the brains of knockout and wild-type H-ras mice showed
      that disruption of this locus did not impair or alter neuronal development.
      Breeding between our H-ras mutant animals and previously available N-ras null
      mutants gave rise to viable double knockout (H-ras(-/-)/N-ras(-/-)) offspring
      expressing only K-ras genes which grew normally, were fertile, and did not show
      any obvious phenotype. Interestingly, however, lower-than-expected numbers of
      adult, double knockout animals were consistently obtained in Mendelian crosses
      between heterozygous N-ras/H-ras mice. Our results indicate that, as for N-ras, H
      ras gene function is dispensable for normal mouse development, growth, fertility,
      and neuronal development. Additionally, of the three ras genes, K-ras appears to
      be not only essential but also sufficient for normal mouse development.

PMID- 11238882
TI  - The Saccharomyces cerevisiae TIF6 gene encoding translation initiation factor 6
      is required for 60S ribosomal subunit biogenesis.
AB  - Eukaryotic translation initiation factor 6 (eIF6), a monomeric protein of about
      26 kDa, can bind to the 60S ribosomal subunit and prevent its association with
      the 40S ribosomal subunit. In Saccharomyces cerevisiae, eIF6 is encoded by a
      single-copy essential gene. To understand the function of eIF6 in yeast cells, we
      constructed a conditional mutant haploid yeast strain in which a functional but a
      rapidly degradable form of eIF6 fusion protein was synthesized from a repressible
      GAL10 promoter. Depletion of eIF6 from yeast cells resulted in a selective
      reduction in the level of 60S ribosomal subunits, causing a stoichiometric
      imbalance in 60S-to-40S subunit ratio and inhibition of the rate of in vivo
      protein synthesis. Further analysis indicated that eIF6 is not required for the
      stability of 60S ribosomal subunits. Rather, eIF6-depleted cells showed defective
      pre-rRNA processing, resulting in accumulation of 35S pre-rRNA precursor,
      formation of a 23S aberrant pre-rRNA, decreased 20S pre-rRNA levels, and
      accumulation of 27SB pre-rRNA. The defect in the processing of 27S pre-rRNA
      resulted in the reduced formation of mature 25S and 5.8S rRNAs relative to 18S
      rRNA, which may account for the selective deficit of 60S ribosomal subunits in
      these cells. Cell fractionation as well as indirect immunofluorescence studies
      showed that c-Myc or hemagglutinin epitope-tagged eIF6 was distributed throughout
      the cytoplasm and the nuclei of yeast cells.

PMID- 11238883
TI  - Autoinhibition mechanism of proto-Dbl.
AB  - The dbl oncogene encodes a prototype member of the Rho GTPase guanine nucleotide
      exchange factor (GEF) family. Oncogenic activation of proto-Dbl occurs through
      truncation of the N-terminal 497 residues. The C-terminal half of proto-Dbl
      includes residues 498 to 680 and 710 to 815, which fold into the Dbl homology
      (DH) domain and the pleckstrin homology (PH) domain, respectively, both of which
      are essential for cell transformation via the Rho GEF activity or cytoskeletal
      targeting function. Here we have investigated the mechanism of the apparent
      negative regulation of proto-Dbl imposed by the N-terminal sequences. Deletion of
      the N-terminal 285 or C-terminal 100 residues of proto-Dbl did not significantly
      affect either its transforming activity or GEF activity, while removal of the N
      terminal 348 amino acids resulted in a significant increase in both
      transformation and GEF potential. Proto-Dbl displayed a mostly perinuclear
      distribution pattern, similar to a polypeptide derived from its N-terminal
      sequences, whereas onco-Dbl colocalized with actin stress fibers, like the PH
      domain. Coexpression of the N-terminal 482 residues with onco-Dbl resulted in
      disruption of its cytoskeletal localization and led to inhibition of onco-Dbl
      transforming activity. The apparent interference with the DH and PH functions by
      the N-terminal sequences can be rationalized by the observation that the N
      terminal 482 residues or a fragment containing residues 286 to 482 binds
      specifically to the PH domain, limiting the access of Rho GTPases to the
      catalytic DH domain and masking the intracellular targeting function of the PH
      domain. Taken together, our findings unveiled an autoinhibitory mode of
      regulation of proto-Dbl that is mediated by the intramolecular interaction
      between its N-terminal sequences and PH domain, directly impacting both the GEF
      function and intracellular distribution.

PMID- 11238884
TI  - Craniofacial dysmorphogenesis including cleft palate in mice with an insertional
      mutation in the discs large gene.
AB  - The discs large (Dlg) protein, or synapse-associated protein 97 (SAP97), is a
      member of the membrane-associated guanylate kinase family of multidomain
      scaffolding proteins which recruits transmembrane and signaling molecules to
      localized plasma membrane sites. Murine dlg is the homologue of the Drosophila
      dlg tumor suppressor gene. The loss of dlg function in Drosophila disrupts
      cellular growth control, apicobasal polarity, and cell adhesion of imaginal disc
      epithelial cells, resulting in embryonic lethality. In this study, we isolated a
      mutational insertion in the murine dlg locus by gene trapping in totipotent
      embryonic stem cells. This insertion results in a truncated protein product that
      contains the N-terminal three PSD-95/DLG/ZO-1 domains of Dlg fused to the LacZ
      reporter and subsequently lacks the src homology 3 (SH3), protein 4.1 binding,
      and guanylate kinase (GUK)-like domains. The Dlg-LacZ fusion protein is expressed
      in epithelial, mesenchymal, neuronal, endothelial, and hematopoietic cells during
      embryogenesis. Mice homozygous for the dlg mutation exhibit growth retardation in
      utero, have hypoplasia of the premaxilla and mandible, have a cleft secondary
      palate, and die perinatally. Consistent with this phenotype, Dlg-LacZ is
      expressed in mesenchymal and epithelial cells throughout palatal development. Our
      genetic and phenotypic analysis of dlg mutant mice suggests that protein-protein
      interactions involving the SH3, protein 4.1 binding, and/or GUK-like domains are
      essential to the normal function of murine Dlg within craniofacial and palatal
      morphogenesis.

PMID- 11238885
TI  - Dach1 mutant mice bear no gross abnormalities in eye, limb, and brain development
      and exhibit postnatal lethality.
AB  - Drosophila dachshund is necessary and sufficient for compound eye development and
      is required for normal leg and brain development. A mouse homologue of dachshund,
      Dach1, is expressed in the developing retina and limbs, suggesting functional
      conservation of this gene. We have generated a loss-of-function mutation in Dach1
      that results in the abrogation of the wild-type RNA and protein expression
      pattern in embryos. Homozygous mutants survive to birth but exhibit postnatal
      lethality associated with a failure to suckle, cyanosis, and respiratory
      distress. The heart, lungs, kidneys, liver, and skeleton were examined to
      identify factors involved in postnatal lethality, but these organs appeared to be
      normal. In addition, blood chemistry tests failed to reveal differences that
      might explain the lethal phenotype. Gross examination and histological analyses
      of newborn eyes, limbs, and brains revealed no detectable abnormalities. Since
      Dach1 mutants die shortly after birth, it remains possible that Dach1 is required
      for postnatal development of these structures. Alternatively, an additional Dach
      homologue may functionally compensate for Dach1 loss of function.

PMID- 11238886
TI  - Insight into mammalian selenocysteine insertion: domain structure and ribosome
      binding properties of Sec insertion sequence binding protein 2.
AB  - The cotranslational incorporation of the unusual amino acid selenocysteine (Sec)
      into both prokaryotic and eukaryotic proteins requires the recoding of a UGA stop
      codon as one specific for Sec. The recognition of UGA as Sec in mammalian
      selenoproteins requires a Sec insertion sequence (SECIS) element in the 3'
      untranslated region as well as the SECIS binding protein SBP2. Here we report a
      detailed analysis of SBP2 structure and function using truncation and site
      directed mutagenesis. We have localized the RNA binding domain to a conserved
      region shared with several ribosomal proteins and eukaryotic translation
      termination release factor 1. We also identified a separate and novel functional
      domain N-terminal to the RNA binding domain which was required for Sec insertion
      but not for SECIS binding. Conversely, we showed that the RNA binding domain was
      necessary but not sufficient for Sec insertion and that the conserved glycine
      residue within this domain was required for SECIS binding. Using glycerol
      gradient sedimentation, we found that SBP2 was stably associated with the
      ribosomal fraction of cell lysates and that this interaction was not dependent on
      its SECIS binding activity. This interaction also occurred with purified
      components in vitro, and we present data which suggest that the SBP2-ribosome
      interaction occurs via 28S rRNA. SBP2 may, therefore, have a distinct function in
      selecting the ribosomes to be used for Sec insertion.

PMID- 11238888
TI  - An upstream AG determines whether a downstream AG is selected during catalytic
      step II of splicing.
AB  - Specific mechanisms must exist to ensure fidelity in selecting the AG
      dinucleotide that functions as the 3' splice site during the second
      transesterification step of splicing. Here we show that the optimal location for
      this AG is within a narrow distance (19 to 23 nucleotides [nt]) downstream from
      the branch point sequence (BPS). Contrary to previous expectations, AGs located
      less than 23 nt from the BPS are always recognized, even when a second AG located
      more optimally downstream is used in the transesterification reaction. Indeed,
      the AG closest to the BPS actually dictates the precise location of the AG that
      engages in the reaction. This mechanism, in which the AG is identified by a
      general localization step followed by a precise localization step, may be used to
      achieve fidelity while allowing flexibility in the location of 3' splice sites.

PMID- 11238887
TI  - Roles of the mitotic inhibitors Wee1 and Mik1 in the G(2) DNA damage and
      replication checkpoints.
AB  - The G(2) DNA damage and DNA replication checkpoints in many organisms act through
      the inhibitory phosphorylation of Cdc2 on tyrosine-15. This phosphorylation is
      catalyzed by the Wee1/Mik1 family of kinases. However, the in vivo role of these
      kinases in checkpoint regulation has been unclear. We show that, in the fission
      yeast Schizosaccharomyces pombe, Mik1 is a target of both checkpoints and that
      the regulation of Mik1 is, on its own, sufficient to delay mitosis in response to
      the checkpoints. Mik1 appears to have two roles in the DNA damage checkpoint; one
      in the establishment of the checkpoint and another in its maintenance. In
      contrast, Wee1 does not appear to be involved in the establishment of either
      checkpoint.

PMID- 11238889
TI  - Upf1p, Nmd2p, and Upf3p regulate the decapping and exonucleolytic degradation of
      both nonsense-containing mRNAs and wild-type mRNAs.
AB  - In Saccharomyces cerevisiae, rapid degradation of nonsense-containing mRNAs
      requires the decapping enzyme Dcp1p, the 5'-to-3' exoribonuclease Xrn1p, and the
      three nonsense-mediated mRNA decay (NMD) factors, Upf1p, Nmd2p, and Upf3p. To
      identify specific functions for the NMD factors, we analyzed the mRNA decay
      phenotypes of yeast strains containing deletions of DCP1 or XRN1 and UPF1, NMD2,
      or UPF3. Our results indicate that Upf1p, Nmd2p, and Upf3p regulate decapping and
      exonucleolytic degradation of nonsense-containing mRNAs. In addition, we show
      that these factors also regulate the same processes in the degradation of wild
      type mRNAs. The participation of the NMD factors in general mRNA degradation
      suggests that they may regulate an aspect of translation termination common to
      all transcripts.

PMID- 11238890
TI  - The B lymphocyte-specific coactivator BOB.1/OBF.1 is required at multiple stages
      of B-cell development.
AB  - The transcriptional coactivator BOB.1/OBF.1 confers B-cell specificity on the
      transcription factors Oct1 and Oct2 at octamer site-containing promoters. A
      hallmark of the BOB.1/OBF.1 mutation in the mouse is the absence of germinal
      center development in secondary lymphoid organs, demonstrating the requirement
      for BOB.1/OBF.1 in antigen-dependent stages of B-cell differentiation. Here we
      analyzed earlier stages of B lymphopoiesis in BOB.1/OBF.1-deficient mice.
      Examination of B-cell development in the bone marrow revealed that the numbers of
      transitional immature (B220(+) IgM(hi)) B cells were reduced and that B-cell
      apoptosis was increased. When in competition with wild-type cells, BOB.1/OBF.1(-/
      ) bone marrow cells exhibited defects in repopulating the bone marrow B-cell
      compartment and were unable to establish a presence in the periphery of host
      mice. The defective bone marrow populations in BOB.1/OBF.1(-/-) mice were rescued
      by conditional expression of a BOB.1/OBF.1 transgene controlled by the
      tetracycline gene expression system. However, the restored populations did not
      restore the numbers of IgD(hi) B cells in the periphery, where the BOB.1/OBF.1
      transgene was not expressed. These results show that BOB.1/OBF.1(-/-) B cells
      exhibit multistage defects in B-cell development, including impaired production
      of transitional B cells and defective maturation of recirculating B cells.

PMID- 11238891
TI  - Grb2 and Shc adapter proteins play distinct roles in Neu (ErbB-2)-induced mammary
      tumorigenesis: implications for human breast cancer.
AB  - Amplification of the Neu (ErbB-2 or HER-2) receptor tyrosine kinase occurs in 20
      to 30% of human mammary carcinomas, correlating with a poor clinical prognosis.
      We have previously demonstrated that four (Y1144 Y1201, Y1227 and Y1253) of the
      five known Neu autophosphorylation sites can independently mediate transforming
      signals. The transforming potential of two of these mutants correlates with their
      capacity to recruit Grb2 directly to Y1144 (YB) or indirectly through Shc to
      Y1227 (YD). Here, we demonstrate that these transformation-competent neu mutants
      activate extracellular signal-regulated kinases and stimulate Ets-2-dependent
      transcription. Although the transforming potential of three of these mutants (YB,
      YD, and YE) was susceptible to inhibition by Rap1A, a genetic antagonist of Ras,
      the transforming potential of YC was resistant to inhibition by Rap1A. To further
      address the significance of these ErbB-2-coupled signaling molecules in induction
      of mammary cancers, transgenic mice expressing mutant Neu receptors lacking the
      known autophosphorylation sites (NYPD) or those coupled directly to either Grb2
      (YB) or Shc (YD) adapter molecules were derived. In contrast to the NYPD strains,
      which developed focal mammary tumors after a long latency period with low
      penetrance, all female mice derived from YB and YD strains rapidly developed
      mammary tumors. Although female mice from several independent YB or YD lines
      developed mammary tumors, the YB strains developed lung metastases at
      substantially higher rates than the YD strains. These observations argue that
      Grb2 and Shc play important and distinct roles in ErbB-2/Neu-induced mammary
      tumorigenesis and metastasis.

PMID- 11238893
TI  - Selective expression of an endogenous inhibitor of FAK regulates proliferation
      and migration of vascular smooth muscle cells.
AB  - Extracellular matrix signaling via integrin receptors is important for smooth
      muscle cell (SMC) differentiation during vasculogenesis and for phenotypic
      modulation of SMCs during atherosclerosis. We previously reported that the
      noncatalytic carboxyl-terminal protein binding domain of focal adhesion kinase
      (FAK) is expressed as a separate protein termed FAK-related nonkinase (FRNK) and
      that ectopic expression of FRNK can attenuate FAK activity and integrin-dependent
      signaling (A. Richardson and J. T. Parsons, Nature 380:538-540, 1996). Herein we
      report that in contrast to FAK, which is expressed ubiquitously, FRNK is
      expressed selectively in SMCs, with particularly high levels observed in conduit
      blood vessels. FRNK expression was low during embryonic development, was
      significantly upregulated in the postnatal period, and returned to low but
      detectable levels in adult tissues. FRNK expression was also dramatically
      upregulated following balloon-induced carotid artery injury. In cultured rat
      aortic smooth muscle cells, overexpression of FRNK attenuated platelet-derived
      growth factor (PDGF)-BB-induced migration and also dramatically inhibited
      [(3)H]thymidine incorporation upon stimulation with PDGF-BB or 10% serum. These
      effects were concomitant with a reduction in SMC proliferation. Taken together,
      these data indicate that FRNK acts as an endogenous inhibitor of FAK signaling in
      SMCs. Furthermore, increased FRNK expression following vascular injury or during
      development may alter the SMC phenotype by negatively regulating proliferative
      and migratory signals.

PMID- 11238892
TI  - Change of the death pathway in senescent human fibroblasts in response to DNA
      damage is caused by an inability to stabilize p53.
AB  - The cellular function of p53 is complex. It is well known that p53 plays a key
      role in cellular response to DNA damage. Moreover, p53 was implicated in cellular
      senescence, and it was demonstrated that p53 undergoes modification in senescent
      cells. However, it is not known how these modifications affect the ability of
      senescent cells to respond to DNA damage. To address this question, we studied
      the responses of cultured young and old normal diploid human fibroblasts to a
      variety of genotoxic stresses. Young fibroblasts were able to undergo p53
      dependent and p53-independent apoptosis. In contrast, senescent fibroblasts were
      unable to undergo p53-dependent apoptosis, whereas p53-independent apoptosis was
      only slightly reduced. Interestingly, instead of undergoing p53-dependent
      apoptosis, senescent fibroblasts underwent necrosis. Furthermore, we found that
      old cells were unable to stabilize p53 in response to DNA damage. Exogenous
      expression or stabilization of p53 with proteasome inhibitors in old fibroblasts
      restored their ability to undergo apoptosis. Our results suggest that
      stabilization of p53 in response to DNA damage is impaired in old fibroblasts,
      resulting in induction of necrosis. The role of this phenomenon in normal aging
      and anticancer therapy is discussed.

PMID- 11238894
TI  - VAMP3 null mice display normal constitutive, insulin- and exercise-regulated
      vesicle trafficking.
AB  - To investigate the physiological function of the VAMP3 vesicle SNARE (v-SNARE)
      isoform in the regulation of GLUT4 vesicle trafficking, we generated homozygotic
      VAMP3 null mice by targeted gene disruption. The VAMP3 null mice had typical
      growth rate and weight gain, with normal maintenance of fasting serum glucose and
      insulin levels. Analysis of glucose disposal and insulin sensitivity demonstrated
      normal insulin and glucose tolerance, with no evidence for insulin resistance.
      Insulin stimulation of glucose uptake in isolated primary adipocytes was
      essentially the same for the wild-type and VAMP3 null mice. Similarly, insulin-,
      hypoxia-, and exercise-stimulated glucose uptake in isolated skeletal muscle did
      not differ significantly. In addition, other general membrane trafficking events
      including phagocytosis, pinocytosis, and transferrin receptor recycling were also
      found to be unaffected in the VAMP3 null mice. Taken together, these data
      demonstrate that VAMP3 function is not necessary for either regulated GLUT4
      translocation or general constitutive membrane recycling.

PMID- 11238895
TI  - Interpretation of X chromosome dose at Sex-lethal requires non-E-box sites for
      the basic helix-loop-helix proteins SISB and daughterless.
AB  - For Drosophila melanogaster flies, sexual fate is determined by the X chromosome
      number. The basic helix-loop-helix protein product of the X-linked sisterlessB
      (sisB or scute) gene is a key indicator of the X dose and functions to activate
      the switch gene Sex-lethal (Sxl) in female (XX), but not in male (XY), embryos.
      Zygotically expressed sisB and maternal daughterless (da) proteins are known to
      form heterodimers that bind E-box sites and activate transcription. We examined
      SISB-Da binding at Sxl by using footprinting and gel mobility shift assays and
      found that SISB-Da binds numerous clustered sites in the establishment promoter
      Sxl(Pe). Surprisingly, most SISB-Da sites at Sxl(Pe) differ from the canonical
      CANNTG E-box motif. These noncanonical sites have 6-bp CA(G/C)CCG and 7-bp
      CA(G/C)CTTG cores and exhibit a range of binding affinities. We show that the
      noncanonical sites can mediate SISB-Da-activated transcription in cell culture. P
      element transformation experiments show that these noncanonical sites are
      essential for Sxl(Pe) activity in embryos. Together with previous deletion
      analysis, the data suggest that the number, affinity, and position of SISB-Da
      sites may all be important for the operation of the Sxl(Pe) switch. Comparisons
      with other dose-sensitive promoters suggest that threshold responses to diverse
      biological signals have common molecular mechanisms, with important variations
      tailored to suit particular functional requirements.

PMID- 11238896
TI  - Analysis of core promoter sequences located downstream from the TATA element in
      the hsp70 promoter from Drosophila melanogaster.
AB  - TFIID recognizes multiple sequence elements in the hsp70 promoter of Drosophila.
      Here, we investigate the function of sequences downstream from the TATA element.
      A mutation in the initiator was identified that caused an eightfold reduction in
      binding of TFIID and a fourfold reduction in transcription in vitro. Another
      mutation in the +24 to +29 region was somewhat less inhibitory, but a mutation in
      the +14 to +19 region had essentially no effect. The normal promoter and the
      mutants in the initiator and the +24 to +29 region were transformed into flies by
      P element-mediated transformation. The initiator mutation reduced expression an
      average of twofold in adult flies, whereas the mutation in the +24 to +29 region
      had essentially no effect. In contrast, a promoter combining the two mutations
      was expressed an average of sixfold less than the wild type. The results suggest
      that the initiator and the +24 to +29 region could serve overlapping functions in
      vivo. Protein-DNA cross-linking was used to identify which subunits of TFIID
      contact the +24 to +29 region and the initiator. No specific subunits were found
      to cross-link to the +24 to +29 region. In contrast, the initiator cross-linked
      exclusively to dTAF230. Remarkably, dTAF230 cross-links approximately 10 times
      more efficiently to the nontranscribed strand than to the transcribed strand at
      the initiator.

PMID- 11238897
TI  - A positive regulator of mitosis, Sok2, functions as a negative regulator of
      meiosis in Saccharomyces cerevisiae.
AB  - The choice between meiosis and alternative developmental pathways in budding
      yeast depends on the expression and activity of transcriptional activator Ime1.
      The transcription of IME1 is repressed in the presence of glucose, and a low
      basal level of IME1 RNA is observed in vegetative cultures with acetate as the
      sole carbon source. IREu, a 32-bp element in the IME1 promoter, exhibits upstream
      activation sequence activity depending on Msn2 and -4 and the presence of
      acetate. We show that in the presence of glucose IREu functions as a negative
      element and that Sok2 mediates this repression activity. We show that Sok2
      associates with Msn2. Sok2 functions as a general repressor whose availability
      and activity depend on glucose. The activity of Sok2 as a repressor depends on
      phosphorylation of T598 by protein kinase A (PKA). Relief of repression of Sok2
      depends on both the N-terminal domain of Sok2 and Ime1. In the absence of glucose
      and the presence of Ime1 Sok2 is converted to a weak activator. Overexpression of
      Sok2 or mild expression of Sok2 with its N-terminal domain deleted leads to a
      decrease in sporulation. Previously it was reported that overexpression of Sok2
      suppresses the growth defect resulting from a temperature-sensitive PKA; thus
      Sok2 has a positive role in mitosis. We show that Candida albicans Efg1, a
      homolog of Sok2, complements sok2 Delta in repressing IREu. Our results
      demonstrate that Sok2, a positive regulator of mitosis, and Efg1, a positive
      regulator of filamentation, function as negative regulators of meiosis. We
      suggest that cells use the same regulators with opposing effects to ensure that
      meiosis will be an alternative to mitosis.

PMID- 11238898
TI  - SH2-B and APS are multimeric adapters that augment TrkA signaling.
AB  - Neurotrophins influence growth and survival of sympathetic and sensory neurons
      through activation of their receptors, Trk receptor tyrosine kinases. Previously,
      we identified Src homology 2-B (SH2-B) and APS, which are structurally similar
      adapter proteins, as substrates of Trk kinases. In the present study, we
      demonstrate that both SH2-B and APS exist in cells as homopentamers and/or
      heteropentamers, independent of Trk receptor activation. Structure-function
      analyses revealed that the SH2-B multimerization domain resides within its amino
      terminus, which is necessary for SH2-B-mediated nerve growth factor (NGF)
      signaling. Overexpression of SH2-B enhances both the magnitude and duration of
      TrkA autophosphorylation following exposure of PC12 cells to NGF, and this effect
      requires the amino-terminal multimerization motif. Moreover, the amino terminus
      of SH2-B is necessary for TrkA/SH2-B-mediated morphological differentiation of
      PC12 cells. Together, these results indicate that the multimeric adapters SH2-B
      and APS influence neurotrophin signaling through direct modulation of Trk
      receptor autophosphorylation.

PMID- 11238899
TI  - Essential role of STAT3 in the control of the acute-phase response as revealed by
      inducible gene inactivation [correction of activation] in the liver.
AB  - We generated mice carrying a STAT3 allele amenable to Cre-mediated deletion and
      intercrossed them with Mx-Cre transgenic mice, in which the expression of Cre
      recombinase can be induced by type I interferon. Interferon-induced deletion of
      STAT3 occurred very efficiently (more than 90%) in the liver and slightly less
      efficiently (about 70%) in the bone marrow. Analysis of the induction of liver
      acute-phase genes in response to bacterial lipopolysaccharide unequivocally
      identifies STAT3 as a fundamental mediator of their induction. The different
      degrees of defectiveness displayed by the various genes allowed us to
      differentiate them into three separate groups according to their degree of
      dependence on STAT3. Induction was totally defective for group I genes, defective
      at 24 h but almost normal at earlier time points for group II genes, and only
      slightly defective for group III genes. This division was in good agreement with
      the known structures of the respective promoters. We also found that the overall
      induction of the transcription factors C/EBP beta and -delta was only minimally
      defective in the absence of STAT3. Finally, even though corticosterone levels and
      action were found to be normal in the conditional-mutant mice, production of both
      proinflammatory and antiinflammatory cytokines was increased and prolonged,
      probably as a result of STAT3 deletion in macrophages.

PMID- 11238900
TI  - Overexpression of SH2-containing inositol phosphatase 2 results in negative
      regulation of insulin-induced metabolic actions in 3T3-L1 adipocytes via its 5'
      phosphatase catalytic activity.
AB  - Phosphatidylinositol (PI) 3-kinase plays an important role in various metabolic
      actions of insulin including glucose uptake and glycogen synthesis. Although PI 3
      kinase primarily functions as a lipid kinase which preferentially phosphorylates
      the D-3 position of phospholipids, the effect of hydrolysis of the key PI 3
      kinase product PI 3,4,5-triphosphate [PI(3,4,5)P3] on these biological responses
      is unknown. We recently cloned rat SH2-containing inositol phosphatase 2 (SHIP2)
      cDNA which possesses the 5'-phosphatase activity to hydrolyze PI(3,4,5)P3 to PI
      3,4-bisphosphate [PI(3,4)P2] and which is mainly expressed in the target tissues
      of insulin. To study the role of SHIP2 in insulin signaling, wild-type SHIP2 (WT
      SHIP2) and 5'-phosphatase-defective SHIP2 (Delta IP-SHIP2) were overexpressed in
      3T3-L1 adipocytes by means of adenovirus-mediated gene transfer. Early events of
      insulin signaling including insulin-induced tyrosine phosphorylation of the
      insulin receptor beta subunit and IRS-1, IRS-1 association with the p85 subunit,
      and PI 3-kinase activity were not affected by expression of either WT-SHIP2 or
      Delta IP-SHIP2. Because WT-SHIP2 possesses the 5'-phosphatase catalytic region,
      its overexpression marked by decreased insulin-induced PI(3,4,5)P3 production, as
      expected. In contrast, the amount of PI(3,4,5)P3 was increased by the expression
      of Delta IP-SHIP2, indicating that Delta IP-SHIP2 functions in a dominant
      negative manner in 3T3-L1 adipocytes. Both PI(3,4,5)P3 and PI(3,4)P2 were known
      to possibly activate downstream targets Akt and protein kinase C lambda in vitro.
      Importantly, expression of WT-SHIP2 inhibited insulin-induced activation of Akt
      and protein kinase C lambda, whereas these activations were increased by
      expression of Delta IP-SHIP2 in vivo. Consistent with the regulation of
      downstream molecules of PI 3-kinase, insulin-induced 2-deoxyglucose uptake and
      Glut4 translocation were decreased by expression of WT-SHIP2 and increased by
      expression of Delta IP-SHIP2. In addition, insulin-induced phosphorylation of GSK
      3beta and activation of PP1 followed by activation of glycogen synthase and
      glycogen synthesis were decreased by expression of WT-SHIP2 and increased by the
      expression of Delta IP-SHIP2. These results indicate that SHIP2 negatively
      regulates metabolic signaling of insulin via the 5'-phosphatase activity and that
      PI(3,4,5)P3 rather than PI(3,4)P2 is important for in vivo regulation of insulin
      induced activation of downstream molecules of PI 3-kinase leading to glucose
      uptake and glycogen synthesis.

PMID- 11238902
TI  - 3'-phosphodiesterase and 3'-->5' exonuclease activities of yeast Apn2 protein and
      requirement of these activities for repair of oxidative DNA damage.
AB  - In Saccharomyces cerevisiae, the AP endonucleases encoded by the APN1 and APN2
      genes provide alternate pathways for the removal of abasic sites. Oxidative DNA
      damaging agents, such as H(2)O(2), produce DNA strand breaks which contain 3'
      phosphate or 3'-phosphoglycolate termini. Such 3' termini are inhibitory to
      synthesis by DNA polymerases. Here, we show that purified yeast Apn2 protein
      contains 3'-phosphodiesterase and 3'-->5' exonuclease activities, and mutation of
      the active-site residue Glu59 to Ala in Apn2 inactivates both these activities.
      Consistent with these biochemical observations, genetic studies indicate the
      involvement of APN2 in the repair of H(2)O(2)-induced DNA damage in a pathway
      alternate to APN1, and the Ala59 mutation inactivates this function of Apn2. From
      these results, we conclude that the ability of Apn2 to remove 3'-end groups from
      DNA is paramount for the repair of strand breaks arising from the reaction of DNA
      with reactive oxygen species.

PMID- 11238901
TI  - Pir1p mediates translocation of the yeast Apn1p endonuclease into the
      mitochondria to maintain genomic stability.
AB  - The mitochondrial genome is continuously subject to attack by reactive oxygen
      species generated through aerobic metabolism. This leads to the formation of a
      variety of highly genotoxic DNA lesions, including abasic sites. Yeast Apn1p is
      localized to the nucleus, where it functions to cleave abasic sites, and apn1
      Delta mutants are hypersensitive to agents such as methyl methanesulfonate (MMS)
      that induce abasic sites. Here we demonstrate for the first time that yeast Apn1p
      is also localized to the mitochondria. We found that Pir1p, initially isolated as
      a cell wall constituent of unknown function, interacts with the C-terminal end of
      Apn1p, which bears a bipartite nuclear localization signal. Further analysis
      revealed that Pir1p is required to cause Apn1p mitochondrial localization,
      presumably by competing with the nuclear transport machinery. pir1 Delta mutants
      displayed a striking (approximately 3-fold) increase of Apn1p in the nucleus,
      which coincided with drastically reduced levels in the mitochondria. To explore
      the functional consequences of the Apn1p-Pir1p interaction, we measured the rate
      of mitochondrial mutations in the wild type and pir1 Delta and apn1 Delta
      mutants. pir1 Delta and apn1 Delta mutants exposed to MMS exhibited 3.6- and 5.8
      fold increases, respectively, in the rate of mitochondrial mutations,
      underscoring the importance of Apn1p in repair of the mitochondrial genome. We
      conclude that Pir1p interacts with Apn1p, at the level of either the cytoplasm or
      nucleus, and facilitates Apn1p transport into the mitochondria to repair damaged
      DNA.

PMID- 11238903
TI  - Zygotic regulation of maternal cyclin A1 and B2 mRNAs.
AB  - At the midblastula transition, the Xenopus laevis embryonic cell cycle is
      remodeled from rapid alternations between S and M phases to become the complex
      adult cell cycle. Cell cycle remodeling occurs after zygotic transcription
      initiates and is accompanied by terminal downregulation of maternal cyclins A1
      and B2. We report here that the disappearance of both cyclin A1 and B2 proteins
      is preceded by the rapid deadenylation of their mRNAs. A specific mechanism
      triggers this deadenylation. This mechanism depends upon discrete regions of the
      3' untranslated regions and requires zygotic transcription. Together, these
      results strongly suggest that zygote-dependent deadenylation of cyclin A1 and
      cyclin B2 mRNAs is responsible for the downregulation of these proteins. These
      studies also raise the possibility that zygotic control of maternal cyclins plays
      a role in establishing the adult cell cycle.

PMID- 11238904
TI  - Functional analysis of the leukemia protein ELL: evidence for a role in the
      regulation of cell growth and survival.
AB  - The ELL gene encodes an RNA polymerase II transcription factor that frequently
      undergoes translocation with the MLL gene in acute human myeloid leukemia. Here,
      we report that ELL can regulate cell proliferation and survival. In order to
      better understand the physiological role of the ELL protein, we have developed an
      ELL-inducible cell line. Cells expressing ELL were uniformly inhibited for growth
      by a loss of the G(1) population and an increase in the G(2)/M population. This
      decrease in cell growth is followed by the condensation of chromosomal DNA,
      activation of caspase 3, poly(ADP ribose) polymerase cleavage, and an increase in
      sub-G(1) population, which are all indicators of the process of programmed cell
      death. In support of the role of ELL in induction of cell death, expression of an
      ELL antisense RNA or addition of the caspase inhibitor ZVAD-fmk results in a
      reversal of ELL-mediated death. We have also demonstrated that the C-terminal
      domain of ELL, which is conserved among the ELL family of proteins that we have
      cloned (ELL, ELL2, and ELL3), is required for ELL's activity in the regulation of
      cell growth. These novel results indicate that ELL can regulate cell growth and
      survival and may explain how ELL translocations result in the development of
      human malignancies.

PMID- 11238905
TI  - Actinin-associated LIM protein-deficient mice maintain normal development and
      structure of skeletal muscle.
AB  - The actinin-associated LIM protein, ALP, is the prototype of a large family of
      proteins containing an N-terminal PDZ domain and a C-terminal LIM domain. These
      PDZ-LIM proteins are components of the muscle cytoskeleton and occur along the Z
      lines owing to interaction of the PDZ domain with the spectrin-like repeats of
      alpha-actinin. Because PDZ and LIM domains are typically found in proteins that
      mediate cellular signaling, PDZ-LIM proteins are suspected to participate in
      muscle development. Interestingly the ALP gene occurs at 4q35 near the
      heterochromatic region mutated in facioscapulohumeral muscular dystrophy,
      indicating a possible role for ALP in this disease. Here, we describe the
      generation and analysis of mice lacking the ALP gene. Surprisingly, the ALP
      knockout mice show no gross histological abnormalities and maintain sarcolemmal
      integrity as determined by serum pyruvate kinase assays. The absence of a
      dystrophic phenotype in these mice suggests that down-regulation of ALP does not
      participate in facioscapulohumeral muscular dystrophy. These data suggest that
      ALP does not participate in muscle development or that an alternative PDZ-LIM
      protein can compensate for the lack of ALP.

PMID- 11238906
TI  - Ambient pH signaling regulates nuclear localization of the Aspergillus nidulans
      PacC transcription factor.
AB  - The Aspergillus nidulans zinc finger transcription factor PacC is activated by
      proteolytic processing in response to ambient alkaline pH. The pH-regulated step
      is the transition of full-length PacC from a closed to an open, protease
      accessible conformation. Here we show that in the absence of ambient pH
      signaling, the C-terminal negative-acting domain prevents the nuclear
      localization of full-length closed PacC. In contrast, the processed PacC form is
      almost exclusively nuclear at any ambient pH. In the presence of ambient pH
      signaling, the fraction of PacC that is in the open conformation but has not yet
      been processed localizes to the nucleus. Therefore, ambient alkaline pH leads to
      an increase in nuclear PacC by promoting the proteolytic elimination of the
      negative-acting domain to yield the processed form and by increasing the
      proportion of full-length protein that is in the open conformation. These
      findings explain why mutations resulting in commitment of PacC to processing
      irrespective of ambient pH lead to permanent PacC activation and alkalinity
      mimicry. A nuclear import signal that targets Escherichia coli beta-galactosidase
      to the nucleus has been located to the PacC zinc finger region. A mutation
      abolishing DNA binding does not prevent nuclear localization of the processed
      form, showing that PacC processing does not lead to nuclear localization by
      passive diffusion of the protein made possible by the reduction in size, followed
      by retention in the nucleus after DNA binding.

PMID- 11238907
TI  - Proteasome inhibition induces nuclear translocation and transcriptional
      activation of the dioxin receptor in mouse embryo primary fibroblasts in the
      absence of xenobiotics.
AB  - The aryl hydrocarbon receptor (AHR) is a transcription factor that is highly
      conserved during evolution and shares important structural features with the
      Drosophila developmental regulators Sim and Per. Although much is known about the
      mechanism of AHR activation by xenobiotics, little information is available
      regarding its activation by endogenous stimuli in the absence of exogenous
      ligand. In this study, using embryonic primary fibroblasts, we have analyzed the
      role of proteasome inhibition on AHR transcriptional activation in the absence of
      xenobiotics. Proteasome inhibition markedly reduced cytosolic AHR without
      affecting its total cellular content. Cytosolic AHR depletion was the result of
      receptor translocation into the nuclear compartment, as shown by transient
      transfection of a green fluorescent protein-tagged AHR and by immunoblot analysis
      of nuclear extracts. Gel retardation experiments showed that proteasome
      inhibition induced transcriptionally active AHR-ARNT heterodimers able to bind to
      a consensus xenobiotic-responsive element. Furthermore, nuclear AHR was
      transcriptionally active in vivo, as shown by the induction of the endogenous
      target gene CYP1A2. Synchronized to AHR activation, proteasome inhibition also
      induced a transient increase in AHR nuclear translocator (ARNT) at the protein
      and mRNA levels. Since nuclear levels of AHR and ARNT are relevant for AHR
      transcriptional activation, our data suggest that proteasome inhibition, through
      a transient increase in ARNT expression, could promote AHR stabilization and
      accumulation into the nuclear compartment. An elevated content of nuclear AHR
      could favor AHR-ARNT heterodimers able to bind to xenobiotic-responsive elements
      and to induce gene transcription in the absence of xenobiotics. Thus, depending
      on the cellular context, physiologically regulated proteasome activity could
      participate in the control of endogenous AHR functions.

PMID- 11238908
TI  - Checkpoint adaptation precedes spontaneous and damage-induced genomic instability
      in yeast.
AB  - Despite the fact that eukaryotic cells enlist checkpoints to block cell cycle
      progression when their DNA is damaged, cells still undergo frequent genetic
      rearrangements, both spontaneously and in response to genotoxic agents. We and
      others have previously characterized a phenomenon (adaptation) in which yeast
      cells that are arrested at a DNA damage checkpoint eventually override this
      arrest and reenter the cell cycle, despite the fact that they have not repaired
      the DNA damage that elicited the arrest. Here, we use mutants that are defective
      in checkpoint adaptation to show that adaptation is important for achieving the
      highest possible viability after exposure to DNA-damaging agents, but it also
      acts as an entree into some forms of genomic instability. Specifically, the
      spontaneous and X-ray-induced frequencies of chromosome loss, translocations, and
      a repair process called break-induced replication occur at significantly reduced
      rates in adaptation-defective mutants. This indicates that these events occur
      after a cell has first arrested at the checkpoint and then adapted to that
      arrest. Because malignant progression frequently involves loss of genes that
      function in DNA repair, adaptation may promote tumorigenesis by allowing genomic
      instability to occur in the absence of repair.

PMID- 11238909
TI  - Phosphorylation and rapid relocalization of 53BP1 to nuclear foci upon DNA
      damage.
AB  - 53BP1 is a human BRCT protein that was originally identified as a p53-interacting
      protein by the Saccharomyces cerevisiae two-hybrid screen. Although the carboxyl
      terminal BRCT domain shows similarity to Crb2, a DNA damage checkpoint protein in
      fission yeast, there is no evidence so far that implicates 53BP1 in the
      checkpoint. We have identified a Xenopus homologue of 53BP1 (XL53BP1). XL53BP1 is
      associated with chromatin and, in some cells, localized to a few large foci under
      normal conditions. Gamma-ray irradiation induces increased numbers of the nuclear
      foci in a dose-dependent manner. The damage-induced 53BP1 foci appear rapidly (in
      30 min) after irradiation, and de novo protein synthesis is not required for this
      response. In human cells, 53BP1 foci colocalize with Mrel1 foci at later stages
      of the postirradiation period. XL53BP1 is hyperphosphorylated after X-ray
      irradiation, and inhibitors of ATM-related kinases delay the relocalization and
      reduce the phosphorylation of XL53BP1 in response to X-irradiation. In AT cells,
      which lack ATM kinase, the irradiation-induced responses of 53BP1 are similarly
      affected. These results suggest a role for 53BP1 in the DNA damage response
      and/or checkpoint control which may involve signaling of damage to p53.

PMID- 11238910
TI  - Cardiomyopathy in Irx4-deficient mice is preceded by abnormal ventricular gene
      expression.
AB  - To define the role of Irx4, a member of the Iroquois family of homeobox
      transcription factors in mammalian heart development and function, we disrupted
      the murine Irx4 gene. Cardiac morphology in Irx4-deficient mice (designated
      Irx4(Delta ex2/Delta ex2)) was normal during embryogenesis and in early postnatal
      life. Adult Irx4(Delta ex2/Delta ex2) mice developed a cardiomyopathy
      characterized by cardiac hypertrophy and impaired contractile function. Prior to
      the development of cardiomyopathy, Irx4(Delta ex2/Delta ex2) hearts had abnormal
      ventricular gene expression: Irx4-deficient embryos exhibited reduced ventricular
      expression of the basic helix-loop-helix transcription factor eHand (Hand1),
      increased Irx2 expression, and ventricular induction of an atrial chamber
      specific transgene. In neonatal hearts, ventricular expression of atrial
      natriuretic factor and alpha-skeletal actin was markedly increased. Several weeks
      subsequent to these changes in embryonic and neonatal gene expression, increased
      expression of hypertrophic markers BNP and beta-myosin heavy chain accompanied
      adult-onset cardiac hypertrophy. Cardiac expression of Irx1, Irx2, and Irx5 may
      partially compensate for loss of Irx4 function. We conclude that Irx4 is not
      sufficient for ventricular chamber formation but is required for the
      establishment of some components of a ventricle-specific gene expression program.
      In the absence of genes under the control of Irx4, ventricular function
      deteriorates and cardiomyopathy ensues.

PMID- 11238911
TI  - TFIIA interacts with TFIID via association with TATA-binding protein and TAF40.
AB  - TFIIA and TATA-binding protein (TBP) associate directly at the TATA element of
      genes transcribed by RNA polymerase II. In vivo, TBP is complexed with
      approximately 14 TBP-associated factors (TAFs) to form the general transcription
      factor TFIID. How TFIIA and TFIID communicate is not well understood. We show
      that in addition to making direct contacts with TBP, yeast TAF40 interacts
      directly and specifically with TFIIA. Mutational analyses of the Toa2 subunit of
      TFIIA indicate that loss of functional interaction between TFIIA and TAF40
      results in conditional growth phenotypes and defects in transcription. These
      results demonstrate that the TFIIA-TAF40 interaction is important in vivo and
      indicate a functional role for TAF40 as a bridging factor between TFIIA and
      TFIID.

PMID- 11238912
TI  - Determinants of CoRNR-dependent repression complex assembly on nuclear hormone
      receptors.
AB  - Ligand-dependent exchange of coactivators and corepressors is the fundamental
      regulator of nuclear hormone receptor (NHR) function. The interaction surfaces of
      coactivators and corepressors are similar but distinct enough to allow the ligand
      to function as a switch. Multiple NHRs share features that allow corepressor
      binding, and each of two distinct corepressors (N-CoR and SMRT) contains two
      similar CoRNR motifs that interact with NHRs. Here we report that the specificity
      of corepressor-NHR interaction is determined by the individual NHR interacting
      with specific CoRNR boxes within a preferred corepressor. First, receptors have
      distinct preferences for CoRNR1 versus CoRNR2. For example, the retinoic acid
      receptor binds CoRNR1, while RXR interacts almost exclusively with CoRNR2.
      Second, the NHR preference for N-CoR or SMRT is due to differences in CoRNR1 but
      not CoRNR2. Moreover, within a single corepressor, affinity for different NHRs is
      determined by distinct regions flanking CoRNR1. The highly specific determinants
      of NHR-corepressor interaction and preference suggest that repression is
      regulated by the permissibility of selected receptor-CoRNR-corepressor
      combinations. Interestingly, different NHR surfaces contribute to binding of
      CoRNR1 and CoRNR2, suggesting a model to explain corepressor binding to NHR
      heterodimers.

PMID- 11238913
TI  - The balance of nuclear import and export determines the intracellular
      distribution and function of tomato heat stress transcription factor HsfA2.
AB  - Tomato heat stress transcription factor HsfA2 is a shuttling protein with
      dominant cytoplasmic localization as a result of a nuclear import combined with
      an efficient export. Besides the nuclear localization signal (NLS) adjacent to
      the oligomerization domain, a C-terminal leucine-rich motif functions as a
      nuclear export signal (NES). Mutant forms of HsfA2 with a defective or an absent
      NES are nuclear proteins. The same is true for the wild-type HsfA2 if coexpressed
      with HsfA1 or in the presence of export inhibitor leptomycin B (LMB). Fusion of
      the NES domain of HsfA2 to HsfB1, which is a nuclear protein, caused export of
      the HsfB1-A2NES hybrid protein, and this effect was reversed by the addition of
      LMB. Due to the lack of background problems, Chinese hamster ovary (CHO) cells
      represent an excellent system for expression and functional analysis of tomato
      Hsfs. The results faithfully reflect the situation found in plant cells (tobacco
      protoplasts). The intriguing role of NLS and NES accessibility for the
      intracellular distribution of HsfA2 is underlined by the results of heat stress
      treatments of CHO cells (41 degrees C). Despite the fact that nuclear import and
      export are not markedly affected, HsfA2 remains completely cytoplasmic at 41
      degrees C even in the presence of LMB. The temperature-dependent conformational
      transition of HsfA2 with shielding of the NLS evidently needs intramolecular
      interaction between the internal HR-A/B and the C-terminal HR-C regions. It is
      not observed with the HR oligomerization domain (HR-A/B region) deletion form of
      HsfA2 or in HsfA2-HsfA1 hetero-oligomers.

PMID- 11238914
TI  - Subtype-specific translocation of the delta subtype of protein kinase C and its
      activation by tyrosine phosphorylation induced by ceramide in HeLa cells.
AB  - We investigated the functional roles of ceramide, an intracellular lipid
      mediator, in cell signaling pathways by monitoring the intracellular movement of
      protein kinase C (PKC) subtypes fused to green fluorescent protein (GFP) in HeLa
      living cells. C(2)-ceramide but not C(2)-dihydroceramide induced translocation of
      delta PKC-GFP to the Golgi complex, while alpha PKC- and zeta PKC-GFP did not
      respond to ceramide. The Golgi-associated delta PKC-GFP induced by ceramide was
      further translocated to the plasma membrane by phorbol ester treatment. Ceramide
      itself accumulated to the Golgi complex where delta PKC was translocated by
      ceramide. Gamma interferon also induced the delta PKC-specific translocation from
      the cytoplasm to the Golgi complex via the activation of Janus kinase and Mg(2+)
      dependent neutral sphingomyelinase. Photobleaching studies showed that ceramide
      does not evoke tight binding of delta PKC-GFP to the Golgi complex but induces
      the continuous association and dissociation of delta PKC with the Golgi complex.
      Ceramide inhibited the kinase activity of delta PKC-GFP in the presence of
      phosphatidylserine and diolein in vitro, while the kinase activity of delta PKC
      GFP immunoprecipitated from ceramide-treated cells was increased. The
      immunoprecipitated delta PKC-GFP was tyrosine phosphorylated after ceramide
      treatment. Tyrosine kinase inhibitor abolished the ceramide-induced activation
      and tyrosine phosphorylation of delta PKC-GFP. These results suggested that gamma
      interferon stimulation followed by ceramide generation through Mg(2+)-dependent
      sphingomyelinase induced delta PKC-specific translocation to the Golgi complex
      and that translocation results in delta PKC activation through tyrosine
      phosphorylation of the enzyme.

PMID- 11238915
TI  - CAC3(MSI1) suppression of RAS2(G19V) is independent of chromatin assembly factor
      I and mediated by NPR1.
AB  - Cac3p/Msi1p, the Saccharomyces cerevisiae homolog of retinoblastoma-associated
      protein 48 (RbAp48), is a component of chromatin assembly factor I (CAF-I), a
      complex that assembles histones H3 and H4 onto replicated DNA. CAC3
      overexpression also suppresses the RAS/cyclic AMP (cAMP) signal transduction
      pathway by an unknown mechanism. We investigated this mechanism and found that
      CAC3 suppression of RAS/cAMP signal transduction was independent of either CAC1
      or CAC2, subunits required for CAF-I function. CAC3 suppression was also
      independent of other chromatin-modifying activities, indicating that Cac3p has at
      least two distinct, separable functions, one in chromatin assembly and one in
      regulating RAS function. Unlike Cac1p, which localizes primarily to the nucleus,
      Cac3p localizes to both the nucleus and the cytoplasm. In addition, Cac3p
      associates with Npr1p, a cytoplasmic kinase that stablizes several nutrient
      transporters by antagonizing a ubiquitin-mediated protein degradation pathway.
      Deletion of NPR1, like overexpression of Cac3p, suppressed the RAS/cAMP pathway.
      Furthermore, NPR1 overexpression interfered with the ability of CAC3 to suppress
      the RAS/cAMP pathway, indicating that extra Cac3p suppresses the RAS/cAMP pathway
      by sequestering Npr1p. Deletion of NPR1 did not affect the quantity,
      phosphorylation state, or localization of Ras2p. Consistent with the idea that
      Npr1p exerts its effect on the RAS/cAMP pathway by antagonizing a ubiquitin
      mediated process, excess ubiquitin suppressed both the heat shock sensitivity and
      the sporulation defects caused by constitutive activation of the RAS/cAMP
      pathway. Thus, CAC3/MSI1 regulates the RAS/cAMP pathway via a chromatin
      independent mechanism that involves the sequestration of Npr1p and may be due to
      the increased ubiquitination of an Npr1p substrate.

PMID- 11238916
TI  - Protein tyrosine phosphatase phi regulates paxillin tyrosine phosphorylation and
      mediates colony-stimulating factor 1-induced morphological changes in
      macrophages.
AB  - Removal of colony-stimulating factor 1 (CSF-1) causes macrophages to round up and
      to increase their expression of protein tyrosine phosphatase phi (PTP phi). This
      is accompanied by the disruption of focal complexes and the formation of ruffles.
      Here we have overexpressed wild-type (WT) PTP phi and a phosphatase-inactive
      (C325S) mutant in a macrophage cell line in the presence and absence of CSF-1. In
      the presence of CSF-1, WT PTP phi induces cell rounding and ruffle formation,
      while C325S PTP phi has no effect. In contrast, in CSF-1-starved cells, C325S PTP
      phi behaves in a dominant negative fashion, preventing rounding and ruffling.
      Furthermore, C325S PTP phi increases adhesion in cycling cells, while WT PTP phi
      enhances motility. In WT PTP phi-overexpressing cells, the focal contact protein
      paxillin is selectively depleted from focal complexes and specifically
      dephosphorylated on tyrosine. In contrast, paxillin is hyperphosphorylated in
      C325S PTP phi-expressing cells. Moreover, a complex containing PTP phi, paxillin,
      and a paxillin-associated tyrosine kinase, Pyk2, can be immunoprecipitated from
      macrophage lysates, and the catalytic domain of PTP phi selectively binds
      paxillin and Pyk2 in vitro. Although PTP phi and Pyk2 do not colocalize with
      paxillin in focal complexes, all three proteins are colocalized in dorsal
      ruffles. The results suggest that paxillin is dephosphorylated by PTP phi in
      dorsal ruffles, using Pyk2 as a bridging molecule, resulting in a reduced pool of
      tyrosine-phosphorylated paxillin available for incorporation into focal
      complexes, thereby mediating CSF-1 regulation of macrophage morphology, adhesion,
      and motility.

PMID- 11238917
TI  - Disruption of the Cockayne syndrome B gene impairs spontaneous tumorigenesis in
      cancer-predisposed Ink4a/ARF knockout mice.
AB  - Cells isolated from individuals with Cockayne syndrome (CS) have a defect in
      transcription-coupled DNA repair, which rapidly corrects certain DNA lesions
      located on the transcribed strand of active genes. Despite this DNA repair
      defect, individuals with CS group A (CSA) or group B (CSB) do not exhibit an
      increased spontaneous or UV-induced cancer rate. In order to investigate the
      effect of CSB deficiency on spontaneous carcinogenesis, we crossed CSB(-/-) mice
      with cancer-prone mice lacking the p16(Ink4a)/p19(ARF) tumor suppressor locus.
      CSB(-/-) mice are sensitive to UV-induced skin cancer but show no increased rate
      of spontaneous cancer. CSB(-/-) Ink4a/ARF(-/-) mice developed 60% fewer tumors
      than Ink4a/ARF(-/-) animals and demonstrated a longer tumor-free latency time
      (260 versus 150 days). Moreover, CSB(-/-) Ink4a/ARF(-/-) mouse embryo fibroblasts
      (MEFs) exhibited a lower colony formation rate after low-density seeding, a lower
      rate of H-Ras-induced transformation, slower proliferation, and a lower mRNA
      synthesis rate than Ink4a/ARF(-/-) MEFs. CSB(-/-) Ink4a/ARF(-/-) MEFs were also
      more sensitive to UV-induced p53 induction and UV-induced apoptosis than were
      Ink4a/ARF(-/-) MEFs. In order to investigate whether the apparent antineoplastic
      effect of CSB gene disruption was caused by sensitization to genotoxin-induced
      (p53-mediated) apoptosis or by p53-independent sequelae, we also generated p53(-/
      ) and CSB(-/-) p53(-/-) MEFs. The CSB(-/-) p53(-/-) MEFs demonstrated lower
      colony formation efficiency, a lower proliferation rate, a lower mRNA synthesis
      rate, and a higher rate of UV-induced cell death than p53(-/-) MEFs.
      Collectively, these results indicate that the antineoplastic effect of CSB gene
      disruption is at least partially p53 independent; it may result from impaired
      transcription or from apoptosis secondary to environmental or endogenous DNA
      damage.

PMID- 11238918
TI  - Two survivor pathways that allow growth in the absence of telomerase are
      generated by distinct telomere recombination events.
AB  - Yeast cells can survive in the absence of telomerase RNA, TLC1, by recombination
      mediated telomere elongation. Two types of survivors, type I and type II, can be
      distinguished by their characteristic telomere patterns. RAD52 is essential for
      the generation of both types of survivors. Deletion of both RAD50 and RAD51
      produces a phenotype similar to that produced by deletion of RAD52. Here we
      examined the effects of the RAD50 and the RAD51 epistasis groups as well as the
      RAD52 homologue, RAD59, on the types of survivors generated in the absence of
      telomerase. rad59 mutations completely abolished the ability to generate type II
      survivors, while rad50 mutations decreased the growth viability of type II
      survivors but did not completely eliminate their appearance. Mutations in RAD51,
      RAD54, and RAD57 had the converse affect: they eliminated the ability of cells to
      generate type I survivors in a tlc1 strain. The triple mutant, tlc1 rad51 rad59,
      was not able to generate survivors. Thus either type I or type II recombination
      pathways can allow cells to survive in the absence of telomerase; however,
      elimination of both pathways in a telomerase mutant leads to the inability to
      elongate telomeres and ultimately cell death.

PMID- 11238919
TI  - Early embryonic lethality in PARP-1 Atm double-mutant mice suggests a functional
      synergy in cell proliferation during development.
AB  - PARP-1 and ATM are both involved in the response to DNA strand breaks, resulting
      in induction of a signaling network responsible for DNA surveillance, cellular
      recovery, and cell survival. ATM interacts with double-strand break repair
      pathways and induces signals resulting in the control of the cell cycle-coupled
      checkpoints. PARP-1 acts as a DNA break sensor in the base excision repair
      pathway of DNA. Mice with mutations inactivating either protein show
      radiosensitivity and high radiation-induced chromosomal aberration frequencies.
      Embryos carrying double mutations of both PARP-1 and Atm genes were generated.
      These mutant embryos show apoptosis in the embryo but not in extraembryonic
      tissues and die at embryonic day 8.0, although extraembryonic tissues appear
      normal for up to 10.5 days of gestation. These results reveal a functional
      synergy between PARP-1 and ATM during a period of embryogenesis when cell cycle
      checkpoints are not active and the embryo is particularly sensitive to DNA
      damage. These results suggest that ATM and PARP-1 have synergistic phenotypes due
      to the effects of these proteins on signaling DNA damage and/or on distinct
      pathways of DNA repair.

PMID- 11238920
TI  - c-myc Internal ribosome entry site activity is developmentally controlled and
      subjected to a strong translational repression in adult transgenic mice.
AB  - The expression of c-myc proto-oncogene, a key regulator of cell proliferation and
      apoptosis, is controlled at different transcriptional and posttranscriptional
      levels. In particular, the c-myc mRNA contains an internal ribosome entry site
      (IRES) able to promote translation initiation independently from the classical
      cap-dependent mechanism. We analyzed the variations of c-myc IRES activity ex
      vivo in different proliferating cell types, and in vivo in transgenic mice
      expressing a bicistronic dual luciferase construct. c-myc IRES efficiency was
      compared to that of encephalomyocarditis virus (EMCV) IRES under the same
      conditions. The c-myc IRES was active but with variable efficiency in all
      transiently transfected cell types; it was also active in the 11-day- old (E11)
      embryo and in some tissues of the E16 embryo. Strikingly, its activity was
      undetected or very low in all adult organs tested. In contrast, EMCV IRES was
      very active in most cell types ex vivo, as well as in embryonic and adult
      tissues. These data suggest a crucial role of IRES in the control of c-myc gene
      expression throughout development, either during embryogenesis where its activity
      might participate in cell proliferation or later on, where its silencing could
      contribute to the downregulation of c-myc expression, whose deregulation leads to
      tumor formation.

PMID- 11238921
TI  - Histone folds mediate selective heterodimerization of yeast TAF(II)25 with TFIID
      components yTAF(II)47 and yTAF(II)65 and with SAGA component ySPT7.
AB  - We show that the yeast TFIID (yTFIID) component yTAF(II)47 contains a histone
      fold domain (HFD) with homology to that previously described for hTAF(II)135.
      Complementation in vivo indicates that the yTAF(II)47 HFD is necessary and
      sufficient for vegetative growth. Mutation of highly conserved residues in the
      alpha1 helix of the yTAF(II)47 HFD results in a temperature-sensitive phenotype
      which can be suppressed by overexpression of yTAF(II)25, as well as by
      yTAF(II)40, yTAF(II)19, and yTAF(II)60. In yeast two-hybrid and bacterial
      coexpression assays, the yTAF(II)47 HFD selectively heterodimerizes with
      yTAF(II)25, which we show contains an HFD with homology to the hTAF(II)28 family
      We additionally demonstrate that yTAF(II)65 contains a functional HFD which also
      selectively heterodimerizes with yTAF(II)25. These results reveal the existence
      of two novel histone-like pairs in yTFIID. The physical and genetic interactions
      described here show that the histone-like yTAF(II)s are organized in at least two
      substructures within TFIID rather than in a single octamer-like structure as
      previously suggested. Furthermore, our results indicate that ySPT7 has an HFD
      homologous to that of yTAF(II)47 which selectively heterodimerizes with
      yTAF(II)25, defining a novel histone-like pair in the SAGA complex.

PMID- 11238922
TI  - HIRA, the human homologue of yeast Hir1p and Hir2p, is a novel cyclin-cdk2
      substrate whose expression blocks S-phase progression.
AB  - Substrates of cyclin-cdk2 kinases contain two distinct primary sequence motifs: a
      cyclin-binding RXL motif and one or more phosphoacceptor sites (consensus
      S/TPXK/R or S/TP). To identify novel cyclin-cdk2 substrates, we searched the
      database for proteins containing both of these motifs. One such protein is human
      HIRA, the homologue of two cell cycle-regulated repressors of histone gene
      expression in Saccharomyces cerevisiae, Hir1p and Hir2p. Here we demonstrate that
      human HIRA is an in vivo substrate of a cyclin-cdk2 kinase. First, HIRA bound to
      and was phosphorylated by cyclin A- and E-cdk2 in vitro in an RXL-dependent
      manner. Second, HIRA was phosphorylated in vivo on two consensus cyclin-cdk2
      phosphoacceptor sites and at least one of these, threonine 555, was
      phosphorylated by cyclin A-cdk2 in vitro. Third, phosphorylation of HIRA in vivo
      was blocked by cyclin-cdk2 inhibitor p21(cip1). Fourth, HIRA became
      phosphorylated on threonine 555 in S phase when cyclin-cdk2 kinases are active.
      Fifth, HIRA was localized preferentially to the nucleus, where active cyclin A-
      and E-cdk2 are located. Finally, ectopic expression of HIRA in cells caused
      arrest in S phase and this is consistent with the notion that it is a cyclin-cdk2
      substrate that has a role in control of the cell cycle.

PMID- 11238923
TI  - Inhibition of Tcf3 binding by I-mfa domain proteins.
AB  - We have determined that I-mfa, an inhibitor of several basic helix-loop-helix
      (bHLH) proteins, and XIC, a Xenopus ortholog of human I-mf domain-containing
      protein that shares a highly conserved cysteine-rich C-terminal domain with I
      mfa, inhibit the activity and DNA binding of the HMG box transcription factor
      XTcf3. Ectopic expression of I-mfa or XIC in early Xenopus embryos inhibited
      dorsal axis specification, the expression of the Tcf3/beta-catenin-regulated
      genes siamois and Xnr3, and the ability of beta-catenin to activate reporter
      constructs driven by Lef/Tcf binding sites. I-mfa domain proteins can regulate
      both the Wnt signaling pathway and a subset of bHLH proteins, possibly
      coordinating the activities of these two critical developmental pathways.

PMID- 11238924
TI  - A subset of tumor-derived mutant forms of p53 down-regulate p63 and p73 through a
      direct interaction with the p53 core domain.
AB  - The p53 protein is related by sequence homology and function to the products of
      two other genes, p63 and p73, that each encode several isoforms. We and others
      have discovered previously that certain tumor-derived mutants of p53 can
      associate and inhibit transcriptional activation by the alpha and beta isoforms
      of p73. In this study we have extended these observations to show that in
      transfected cells a number of mutant p53 proteins could bind and down-regulate
      several isoforms not only of p73 (p73 alpha, -beta, -gamma, and -delta) but also
      of p63 (p63 alpha and -gamma; Delta Np63 alpha and -gamma). Moreover, a
      correlation existed between the efficiency of p53 binding and the inhibition of
      p63 or p73 function. We also found that wild-type p63 and p73 interact
      efficiently with each other when coexpressed in mammalian cells. The interaction
      between p53 mutants and p63 or p73 was confirmed in a physiological setting by
      examining tumor cell lines that endogenously express these proteins. We also
      demonstrated that purified p53 and p73 proteins interact directly and that the
      p53 core domain, but not the tetramerization domain, mediates this interaction.
      Using a monoclonal antibody (PAb240) that recognizes an epitope within the core
      domain of a subset of p53 mutants, we found a correlation between the ability of
      p53 proteins to be immunoprecipitated by this antibody and their ability to
      interact with p73 or p63 in vitro and in transfected cells. Based on these
      results and those of others, we propose that interactions between the members of
      the p53 family are likely to be widespread and may account in some cases for the
      ability of tumor-derived p53 mutants to promote tumorigenesis.

PMID- 11238926
TI  - New ways of initiating translation in eukaryotes?

PMID- 11238925
TI  - Functional regions of human telomerase reverse transcriptase and human telomerase
      RNA required for telomerase activity and RNA-protein interactions.
AB  - Telomerase is a specialized reverse transcriptase (RT) that is minimally composed
      of a protein catalytic subunit and an RNA component. The RNA subunit contains a
      short template sequence that directs the synthesis of DNA repeats at the ends of
      chromosomes. Human telomerase activity can be reconstituted in vitro by the
      expression of the human telomerase protein catalytic subunit (hTERT) in the
      presence of recombinant human telomerase RNA (hTR) in a rabbit reticulocyte
      lysate (RRL) system. We analyzed telomerase activity and binding of hTR to hTERT
      in RRL by expressing different hTERT and hTR variants. hTRs containing nucleotide
      substitutions that are predicted to disrupt base pairing in the P3 helix of the
      pseudoknot weakly reconstituted human telomerase activity yet retained their
      ability to bind hTERT. Our results also identified two distinct regions of hTR
      that can independently bind hTERT in vitro. Furthermore, sequences or structures
      between nucleotides 208 and 330 of hTR (which include the conserved CR4-CR5
      domain) were found to be important for hTERT-hTR interactions and for telomerase
      activity reconstitution. Human TERT carboxy-terminal amino acid deletions
      extending to motif E or the deletion of the first 280 amino acids abolished human
      telomerase activity without affecting the ability of hTERT to associate with hTR,
      suggesting that the RT and RNA binding functions of hTERT are separable. These
      results indicate that the reconstitution of human telomerase activity in vitro
      requires regions of hTERT that (i) are distinct from the conserved RT motifs and
      (ii) bind nucleotides distal to the hTR template sequence.

PMID- 11238927
TI  - Modular structure of PACT: distinct domains for binding and activating PKR.
AB  - PACT is a 35-kDa human protein that can directly bind and activate the latent
      protein kinase, PKR. Here we report that PKR activation by PACT causes cellular
      apoptosis in addition to PKR autophosphorylation and translation inhibition. We
      analyzed the structure-function relationship of PACT by measuring its ability to
      bind and activate PKR in vitro and in vivo. Our studies revealed that among three
      domains of PACT, the presence of either domain 1 or domain 2 was sufficient for
      high-affinity binding of PACT to PKR. On the other hand, domain 3, consisting of
      66 residues, was absolutely required for PKR activation in vitro and in vivo.
      When fused to maltose-binding protein, domain 3 was also sufficient for
      efficiently activating PKR in vitro. However, it bound poorly to PKR at the
      physiological salt concentration and consequently could not activate it properly
      in vivo. As anticipated, activation of PKR by domain 3 in vivo could be restored
      by attaching it to a heterologous PKR-binding domain. These results demonstrated
      that the structure of PACT is modular: it is composed of a distinct PKR
      activation domain and two mutually redundant PKR-interacting domains.

PMID- 11238928
TI  - Coordinated regulation of Rap1 and thyroid differentiation by cyclic AMP and
      protein kinase A.
AB  - Originally identified as an antagonist of Ras action, Rap1 exhibits many Ras
      independent effects, including a role in signaling pathways initiated by cyclic
      AMP (cAMP). Since cAMP is a critical mediator of the effects of thyrotropin (TSH)
      on cell proliferation and differentiation, we examined the regulation of Rap1 by
      TSH in a continuous line of rat thyroid-like cells. Both cAMP and protein kinase
      A (PKA) contribute to the regulation of Rap1 activity and signaling by TSH. TSH
      activates Rap1 through a cAMP-mediated and PKA-independent mechanism. TSH
      phosphorylates Rap1 in a PKA-dependent manner. Interference with PKA activity
      blocked phosphorylation but not the activation of Rap1. Rather, PKA inhibitors
      prolonged Rap1 activation, as did expression of a Rap1A mutant lacking a PKA
      phosphorylation site. These results indicate that PKA elicits negative feedback
      regulation on cAMP-stimulated Rap1 activity in some cells. The dual regulation of
      Rap1 by cAMP and PKA extends to downstream effectors. The ability of TSH to
      stimulate Akt phosphorylation was markedly enhanced by the expression of
      activated Rap1A and was repressed in cells expressing a putative dominant
      negative Rap1A mutant. Although the expression of activated Rap1A was sufficient
      to stimulate wortmannin-sensitive Akt phosphorylation, TSH further increased Akt
      phosphorylation in a phosphatidylinositol 3-kinase- and PKA-dependent manner. The
      ability of TSH to phosphorylate Akt was impaired in cells expressing a Rap1A
      mutant that could be activated but not phosphorylated. These findings indicate
      that dual signals, Rap1 activation and phosphorylation, contribute to TSH
      stimulated Akt phosphorylation. Rap1 plays an essential role in cAMP-regulated
      differentiation. TSH effects on thyroid-specific gene expression, but not its
      effects on proliferation, were markedly enhanced in cells expressing activated
      Rap1A and repressed in cells expressing a dominant-negative Rap1A mutant. These
      findings reveal complex regulation of Rap1 by cAMP including PKA-independent
      activation and PKA-dependent negative feedback regulation. Both signals appear to
      be required for TSH signaling to Akt.

PMID- 11238930
TI  - Role of the 3' splice site in U12-dependent intron splicing.
AB  - U12-dependent introns containing alterations of the 3' splice site AC
      dinucleotide or alterations in the spacing between the branch site and the 3'
      splice site were examined for their effects on splice site selection in vivo and
      in vitro. Using an intron with a 5' splice site AU dinucleotide, any nucleotide
      could serve as the 3'-terminal nucleotide, although a C residue was most active,
      while a U residue was least active. The penultimate A residue, by contrast, was
      essential for 3' splice site function. A branch site-to-3' splice site spacing of
      less than 10 or more than 20 nucleotides strongly activated alternative 3' splice
      sites. A strong preference for a spacing of about 12 nucleotides was observed.
      The combined in vivo and in vitro results suggest that the branch site is
      recognized in the absence of an active 3' splice site but that formation of the
      prespliceosomal complex A requires an active 3' splice site. Furthermore, the U12
      type spliceosome appears to be unable to scan for a distal 3' splice site.

PMID- 11238931
TI  - A truncated form of the human CAF-1 p150 subunit impairs the maintenance of
      transcriptional gene silencing in mammalian cells.
AB  - Chromatin assembly factor 1 (CAF-1) is a protein complex formed of three
      subunits, p150, p60, and p48, conserved from the yeast Saccharomyces cerevisiae
      to humans, which can promote nucleosome assembly onto newly replicated DNA. In S.
      cerevisiae, deletion of the genes encoding any of the three CAF-1 subunits
      (cacDelta mutants), although nonlethal, results in a silencing defect of genes
      packaged into heterochromatin. Here we report on a mammalian cell model that we
      devised to monitor gene silencing and its reversal in a quantitative manner. This
      model relies on the use of a cell line stably transfected with a reporter gene in
      a silenced state. Reversal of reporter gene silencing was achieved upon treatment
      of the cells with 5-azacytidine, which resulted in the demethylation of the
      reporter gene copies. We show that expression of a cDNA for the human p150 CAF-1
      subunit harboring 5' truncations, but not that of a cDNA encoding the full-length
      p150 CAF-1 subunit, increases by more than 500-fold the frequency at which
      transcriptional silencing of the reporter gene copies is reversed in these cells.
      Reversal of gene silencing is dependent upon expression of a truncated protein,
      possibly acting as a dominant negative mutant of the wild-type CAF-1, is
      associated with alterations in chromatin structure as measured by an endonuclease
      sensitivity assay and is not associated with detectable changes in the
      methylation status of the silenced genes. These results suggest that the role of
      CAF-1 in the epigenetic control of gene expression has been conserved between
      yeast and mammals, despite the lack of DNA methylation in yeast chromatin.

PMID- 11238929
TI  - IkappaB kinase-dependent chronic activation of NF-kappaB is necessary for
      p21(WAF1/Cip1) inhibition of differentiation-induced apoptosis of monocytes.
AB  - The molecular mechanisms regulating monocyte differentiation to macrophages
      remain unknown. Although the transcription factor NF-kappaB participates in
      multiple cell functions, its role in cell differentiation is ill defined. Since
      differentiated macrophages, in contrast to cycling monocytes, contain significant
      levels of NF-kappaB in the nuclei, we questioned whether this transcription
      factor is involved in macrophage differentiation. Phorbol 12-myristate 13-acetate
      (PMA)-induced differentiation of the promonocytic cell line U937 leads to
      persistent NF-kappaB nuclear translocation. We demonstrate here that an increased
      and persistent IKK activity correlates with monocyte differentiation leading to
      persistent NF-kappaB activation secondary to increased IkappaBalpha degradation
      via the IkappaB signal response domain (SRD). Promonocytic cells stably
      overexpressing an IkappaBalpha transgene containing SRD mutations fail to
      activate NF-kappaB and subsequently fail to survive the PMA-induced macrophage
      differentiation program. The differentiation-induced apoptosis was found to be
      dependent on tumor necrosis factor alpha. The protective effect of NF-kappaB is
      mediated through p21(WAF1/Cip1), since this protein was found to be regulated in
      an NF-kappaB-dependent manner and to confer survival features during macrophage
      differentiation. Therefore, NF-kappaB plays a key role in cell differentiation by
      conferring cell survival that in the case of macrophages is mediated through
      p21(WAF1/Cip1).

PMID- 11238932
TI  - The winged-helix protein brain factor 1 interacts with groucho and hes proteins
      to repress transcription.
AB  - Brain factor 1 (BF-1) is a winged-helix transcriptional repressor that plays
      important roles in both progenitor cell differentiation and regional patterning
      in the mammalian telencephalon. The aim of this study was to elucidate the
      molecular mechanisms underlying BF-1 functions. It is shown here that BF-1
      interacts in vivo with global transcriptional corepressors of the Groucho family
      and also associates with the histone deacetylase 1 protein. The ability of BF-1
      to mediate transcriptional repression is promoted by Groucho and inhibited by the
      histone deacetylase inhibitor trichostatin A, suggesting that BF-1 recruits
      Groucho and histone deacetylase activities to repress transcription. Our studies
      also provide the first demonstration that Groucho mediates a specific interaction
      between BF-1 and the basic helix-loop-helix protein Hes1 and that BF-1
      potentiates transcriptional repression by Hes1 in a Groucho-dependent manner.
      These findings suggest that Groucho participates in the transcriptional functions
      of BF-1 by acting as both a corepressor and an adapter between BF-1 and Hes1.
      Taken together with the demonstration that these proteins are coexpressed in
      telencephalic neural progenitor cells, these results also suggest that complexes
      of BF-1, Groucho, and Hes factors may be involved in the regulation of progenitor
      cell differentiation in the telencephalon.

PMID- 11238933
TI  - Antisense promoter of human L1 retrotransposon drives transcription of adjacent
      cellular genes.
AB  - In the human genome, retrotranspositionally competent long interspersed nuclear
      elements (L1Hs) are involved in the generation of processed pseudogenes and
      mobilization of unrelated sequences into existing genes. Transcription of each
      L1Hs is initiated from its internal promoter but may also be driven from the
      promoters of adjacent cellular genes. Here I show that a hitherto unknown L1Hs
      antisense promoter (ASP) drives the transcription of adjacent genes. The ASP is
      located in the L1Hs 5' untranslated region (5'UTR) and works in the opposite
      direction. Fifteen cDNAs, isolated from a human NTera2D1 cDNA library by a
      differential screening method, contained L1Hs 5'UTRs spliced to the sequences of
      known genes or non-proteincoding sequences. Four of these chimeric transcripts,
      selected for detailed analysis, were detected in total RNA of different cell
      lines. Their abundance accounted for roughly 1 to 500% of the transcripts of four
      known genes, suggesting a large variation in the efficiency of L1Hs ASP-driven
      transcription. ASP-directed transcription was also revealed from expressed
      sequence tag sequences and confirmed by using an RNA dot blot analysis. Nine of
      the 15 randomly selected genomic L1Hs 5'UTRs had ASP activities about 7- to 50
      fold higher than background in transient transfection assays. ASP was assigned to
      the L1Hs 5'UTR between nucleotides 400 to 600 by deletion and mutation analysis.
      These results indicate that many L1Hs contain active ASPs which are capable of
      interfering with normal gene expression, and this type of transcriptional control
      may be widespread.

PMID- 11238934
TI  - Switch in 3' splice site recognition between exon definition and splicing
      catalysis is important for sex-lethal autoregulation.
AB  - Maintenance of female sexual identity in Drosophila melanogaster involves an
      autoregulatory loop in which the protein Sex-lethal (SXL) promotes skipping of
      exon 3 from its own pre-mRNA. We have used transient transfection of Drosophila
      Schneider cells to analyze the role of exon 3 splice sites in regulation. Our
      results indicate that exon 3 repression requires competition between the 5'
      splice sites of exons 2 and 3 but is independent of their relative strength. Two
      3' splice site AG's precede exon 3. We report here that, while the distal site
      plays a critical role in defining the exon, the proximal site is preferentially
      used for the actual splicing reaction, arguing for a switch in 3' splice site
      recognition between exon definition and splicing catalysis. Remarkably, the
      presence of the two 3' splice sites is important for the efficient regulation by
      SXL, suggesting that SXL interferes with molecular events occurring between
      initial splice site communication across the exon and the splice site pairing
      that leads to intron removal.

PMID- 11238935
TI  - Dosage suppressors of pds1 implicate ubiquitin-associated domains in checkpoint
      control.
AB  - In budding yeast, anaphase initiation is controlled by ubiquitin-dependent
      degradation of Pds1p. Analysis of pds1 mutants implicated Pds1p in the DNA
      damage, spindle assembly, and S-phase checkpoints. Though some components of
      these pathways are known, others remain to be identified. Moreover, the essential
      function of Pds1p, independent of its role in checkpoint control, has not been
      elucidated. To identify loci that genetically interact with PDS1, we screened for
      dosage suppressors of a temperature-sensitive pds1 allele, pds1-128, defective
      for checkpoint control at the permissive temperature and essential for viability
      at 37 degrees C. Genetic and functional interactions of two suppressors are
      described. RAD23 and DDI1 suppress the temperature and hydroxyurea, but not
      radiation or nocodazole, sensitivity of pds1-128. rad23 and ddi1 mutants are
      partially defective in S-phase checkpoint control but are proficient in DNA
      damage and spindle assembly checkpoints. Therefore, Rad23p and Ddi1p participate
      in a subset of Pds1p-dependent cell cycle controls. Both Rad23p and Ddi1p contain
      ubiquitin-associated (UBA) domains which are required for dosage suppression of
      pds1-128. UBA domains are found in several proteins involved in ubiquitin
      dependent proteolysis, though no function has been assigned to them. Deletion of
      the UBA domains of Rad23p and Ddi1p renders cells defective in S-phase checkpoint
      control, implicating UBA domains in checkpoint signaling. Since Pds1p
      destruction, and thus checkpoint regulation of mitosis, depends on ubiquitin
      dependent proteolysis, we propose that the UBA domains functionally interact with
      the ubiquitin system to control Pds1p degradation in response to checkpoint
      activation.

PMID- 11238936
TI  - Mutations in the RNA binding domain of stem-loop binding protein define separable
      requirements for RNA binding and for histone pre-mRNA processing.
AB  - Expression of replication-dependent histone genes at the posttranscriptional
      level is controlled by stem-loop binding protein (SLBP). One function of SLBP is
      to bind the stem-loop structure in the 3' untranslated region of histone pre
      mRNAs and facilitate 3' end processing. Interaction of SLBP with the stem-loop is
      mediated by the centrally located RNA binding domain (RBD). Here we identify
      several highly conserved amino acids in the RBD mutation of which results in
      complete or substantial loss of SLBP binding activity. We also identify residues
      in the RBD which do not contribute to binding to the stem-loop RNA but instead
      are required for efficient recruitment of U7 snRNP to histone pre-mRNA.
      Recruitment of the U7 snRNP to the pre-mRNA also depends on the 20-amino-acid
      region located immediately downstream of the RBD. A critical region of the RBD
      contains the sequence YDRY. The tyrosines are required for RNA binding, and the
      DR dipeptide is essential for processing but not for RNA binding. It is likely
      that the RBD of SLBP interacts directly with both the stem-loop RNA and other
      processing factor(s), most likely the U7 snRNP, to facilitate histone pre-mRNA
      processing.

PMID- 11238937
TI  - Acidic residues critical for the activity and biological function of yeast DNA
      polymerase eta.
AB  - Rad30 is a member of the newly discovered UmuC/DinB/Rad30 family of DNA
      polymerases. The N-terminal regions of these proteins are highly homologous, and
      they contain five conserved motifs, I to V, while their C-terminal regions are
      quite divergent. We examined the contributions of the C-terminal and N-terminal
      regions of Rad30 to its activity and biological function. Although deletion of
      the last 54 amino acids has no effect on DNA polymerase or thymine-thymine (T-T)
      dimer bypass activity, this C-terminal deletion-containing protein is unable to
      perform its biological function in vivo. The presence of a bipartite nuclear
      targeting sequence within this region suggests that at least one function of this
      portion of Rad30 is nuclear targeting. To identify the active-site residues of
      Rad30 important for catalysis, we generated mutations of nine acidic residues
      that are invariant or highly conserved among Rad30 proteins from different
      eukaryotic species. Mutations of the Asp30 and Glu39 residues present in motif I
      and of the Asp155 residue present in motif III to alanine completely inactivated
      the DNA polymerase and T-T dimer bypass activities, and these mutations did not
      complement the UV sensitivity of the rad30Delta mutation. Mutation of Glu156 in
      motif III to alanine confers a large reduction in the efficiency of nucleotide
      incorporation, whereas the remaining five Rad30 mutant proteins retain wild-type
      levels of DNA polymerase and T-T dimer bypass activities. From these
      observations, we suggest a role for the Asp30, Glu39, and Asp155 residues in the
      binding of two metal ions required for the reaction of the incoming
      deoxynucleoside 5'-triphosphate with the 3'-hydroxyl in the primer terminus,
      while Glu156 may participate in nucleotide binding.

PMID- 11238938
TI  - Fip1 regulates the activity of Poly(A) polymerase through multiple interactions.
AB  - Fip1 is an essential component of the Saccharomyces cerevisiae polyadenylation
      machinery and the only protein known to interact directly with poly(A) polymerase
      (Pap1). Its association with Pap1 inhibits the extension of an oligo(A) primer by
      limiting access of the RNA substrate to the C-terminal RNA binding domain (C-RBD)
      of Pap1. We present here the identification of separate functional domains of
      Fip1. Amino acids 80 to 105 are required for binding to Pap1 and for the
      inhibition of Pap1 activity. This region is also essential for viability,
      suggesting that Fip1-mediated repression of Pap1 has a crucial physiological
      function. Amino acids 206 to 220 of Fip1 are needed for the interaction with the
      Yth1 subunit of the complex and for specific polyadenylation of the cleaved mRNA
      precursor. A third domain within amino acids 105 to 206 helps to limit RNA
      binding at the C-RBD of Pap1. Our data demonstrate that the C terminus of Fip1 is
      required to relieve the Fip1-mediated repression of Pap1 in specific
      polyadenylation. In the absence of this domain, Pap1 remains in an inhibited
      state. These findings show that Fip1 has a crucial regulatory function in the
      polyadenylation reaction by controlling the activity of poly(A) tail synthesis
      through multiple interactions within the polyadenylation complex.

PMID- 11238939
TI  - A C-terminal region of RAG1 contacts the coding DNA during V(D)J recombination.
AB  - The site-specific DNA rearrangement process, called V(D)J recombination, creates
      much of the diversity of immune receptor molecules in the adaptive immune system.
      Central to this reaction is the organization of the protein-DNA complex
      containing the proteins RAG1 and RAG2 and their DNA targets. A long-term goal is
      to appreciate the three-dimensional relationships between the proteins and DNA
      that allow the assembly of the appropriate reaction intermediates, resulting in
      concerted cleavage and directed rejoining of the DNA ends. Previous cross-linking
      approaches have mapped RAG1 contacts on the DNA. RAG1 protein contacts the DNA at
      the conserved heptamer and nonamer sequences as well as at the coding DNA
      adjacent to the heptamer. Here we subject RAG1, covalently cross-linked to DNA
      substrates, to partial cyanogen bromide degradation or trypsin proteolysis in
      order to map contacts on the protein. We find that coding-sequence contacts occur
      near the C terminus of RAG1, while contacts made within the recombination signal
      sequence occur nearer the N terminus of the core region of RAG1. A deletion
      protein lacking the C-terminal DNA-contacting region is still capable of making
      the N-terminal contacts. This suggests that the two binding interactions may
      exist on two separate domains of the protein. A trypsin cleavage pattern of the
      native protein supports this conclusion. A two-domain model for RAG1 is evaluated
      with respect to the larger recombination complex.

PMID- 11238940
TI  - Genetic requirements for RAD51- and RAD54-independent break-induced replication
      repair of a chromosomal double-strand break.
AB  - Broken chromosomes can be repaired by several homologous recombination
      mechanisms, including gene conversion and break-induced replication (BIR). In
      Saccharomyces cerevisiae, an HO endonuclease-induced double-strand break (DSB) is
      normally repaired by gene conversion. Previously, we have shown that in the
      absence of RAD52, repair is nearly absent and diploid cells lose the broken
      chromosome; however, in cells lacking RAD51, gene conversion is absent but cells
      can repair the DSB by BIR. We now report that gene conversion is also abolished
      when RAD54, RAD55, and RAD57 are deleted but BIR occurs, as with rad51Delta
      cells. DSB-induced gene conversion is not significantly affected when RAD50,
      RAD59, TID1 (RDH54), SRS2, or SGS1 is deleted. Various double mutations largely
      eliminate both gene conversion and BIR, including rad51Delta rad50Delta,
      rad51Delta rad59Delta, and rad54Delta tid1Delta. These results demonstrate that
      there is a RAD51- and RAD54-independent BIR pathway that requires RAD59, TID1,
      RAD50, and presumably MRE11 and XRS2. The similar genetic requirements for BIR
      and telomere maintenance in the absence of telomerase also suggest that these two
      processes proceed by similar mechanisms.

PMID- 11238941
TI  - Identification of the Sin3-binding site in Ume6 defines a two-step process for
      conversion of Ume6 from a transcriptional repressor to an activator in yeast.
AB  - The DNA-binding protein Ume6 is required for both repression and activation of
      meiosis-specific genes, through interaction with the Sin3 corepressor and Rpd3
      histone deacetylase and the meiotic activator Ime1. Here we show that fusion of a
      heterologous activation domain to Ume6 is unable to convert it into a
      constitutive activator of early meiotic gene transcription, indicating that an
      additional function is needed to overcome repression at these promoters.
      Mutations in UME6 allowing the fusion to activate lie in a predicted amphipathic
      alpha helix and specifically disrupt interaction with Sin3 but not with Teal, an
      activator of Ty transcription also found to interact with Ume6 in a two-hybrid
      screen. The mutations cause a loss of repression by Ume6 and precisely identify
      the Ume6 Sin3-binding domain, which we show interacts with the paired amphipathic
      helix 2 region of Sin3. Analysis of these mutants indicates that conversion of
      Ume6 to an activator involves two genetically distinct steps that act to relieve
      Sin3-mediated repression and provide an activation domain to Ume6. The mutants
      further demonstrate that premature expression and lack of subsequent rerepression
      of Ume6-Sin3-regulated genes are not deleterious to meiotic progression and
      suggest that the essential role of Sin3 in meiosis is independent of Ume6. The
      model for Ume6 function arising from these studies indicates that Ume6 is similar
      in many respects to metazoan regulators that utilize Sin3, such as the Myc-Mad
      Max system and nuclear hormone receptors, and provides new insights into the
      control of transcriptional repression and activation by the Ume6-URS1 regulatory
      complex in yeast.

PMID- 11238942
TI  - Identification of a novel AU-Rich element in the 3' untranslated region of
      epidermal growth factor receptor mRNA that is the target for regulated RNA
      binding proteins.
AB  - The epidermal growth factor receptor (EGF-R) plays an important role in the
      growth and progression of estrogen receptor-negative human breast cancers. EGF
      binds with high affinity to the EGF-R and activates a variety of second messenger
      pathways that affect cellular proliferation. However, the underlying mechanisms
      involved in the regulation of EGF-R expression in breast cancer cells are yet to
      be described. Here we show that the EGF-induced upregulation of EGF-R mRNA in two
      human breast cancer cell lines that overexpress EGF-R (MDA-MB-468 and BT-20) is
      accompanied by stabilization (>2-fold) of EGF-R mRNA. Transient transfections
      using a luciferase reporter identified a novel EGF-regulated approximately 260
      nucleotide (nt) cis-acting element in the 3' untranslated region (3'-UTR) of EGF
      R mRNA. This cis element contains two distinct AU-rich sequences (~75 nt), EGF
      R1A with two AUUUA pentamers and EGF-R2A with two AUUUUUA extended pentamers.
      Each independently regulated the mRNA stability of the heterologous reporter.
      Analysis of mutants of the EGF-R2A AU-rich sequence demonstrated a role for the
      3' extended pentamer in regulating basal turnover. RNA gel shift analysis
      identified cytoplasmic proteins (~55 to 80 kDa) from breast cancer cells that
      bound specifically to the EGF-R1A and EGF-R2A cis-acting elements and whose
      binding activity was rapidly downregulated by EGF and phorbol esters. RNA gel
      shift analysis of EGF-R2A mutants identified a role for the 3' extended AU
      pentamer, but not the 5' extended pentamer, in binding proteins. These EGF-R mRNA
      binding proteins were present in multiple human breast and prostate cancer cell
      lines. In summary, these data demonstrate a central role for mRNA stabilization
      in the control of EGF-R gene expression in breast cancer cells. EGF-R mRNA
      contains a novel complex AU-rich 260-nt cis-acting destabilizing element in the
      3'-UTR that is bound by specific and EGF-regulated trans-acting factors.
      Furthermore, the 3' extended AU pentamer of EGF-R2A plays a central role in
      regulating EGF-R mRNA stability and the binding of specific RNA-binding proteins.
      These findings suggest that regulated RNA-protein interactions involving this
      novel cis-acting element will be a major determinant of EGF-R mRNA stability.

PMID- 11238943
TI  - The neuron-restrictive silencer element-neuron-restrictive silencer factor system
      regulates basal and endothelin 1-inducible atrial natriuretic peptide gene
      expression in ventricular myocytes.
AB  - Induction of the atrial natriuretic peptide (ANP) gene is a common feature of
      ventricular hypertrophy. A number of cis-acting enhancer elements for several
      transcriptional activators have been shown to play central roles in the
      regulation of ANP gene expression, but much less is known about contributions
      made by transcriptional repressors. The neuron-restrictive silencer element
      (NRSE), also known as repressor element 1, mediates repression of neuronal gene
      expression in nonneuronal cells. We found that NRSE, which is located in the 3'
      untranslated region of the ANP gene, mediated repression of ANP promoter activity
      in ventricular myocytes and was also involved in the endothelin 1-induced
      increase in ANP gene transcription. The repression was conferred by a repressor
      protein, neuron-restrictive silencer factor (NRSF). NRSF associated with the
      transcriptional corepressor mSin3 and formed a complex with histone deacetylase
      (HDAC) in ventricular myocytes. Trichostatin A (TSA), a specific HDAC inhibitor,
      relieved NRSE-mediated repression of ANP promoter activity, and chromatin
      immunoprecipitation assays revealed the involvement of histone deacetylation in
      NRSE-mediated repression of ANP gene expression. Furthermore, in myocytes
      infected with recombinant adenovirus expressing a dominant-negative form of NRSF,
      the basal level of endogenous ANP gene expression was increased and a TSA-induced
      increase in ANP gene expression was apparently attenuated, compared with those in
      myocytes infected with control adenovirus. Our findings show that an NRSE-NRSF
      system plays a key role in the regulation of ANP gene expression by HDAC in
      ventricular myocytes and provide a new insight into the role of the NRSE-NRSF
      system outside the nervous system.

PMID- 11238944
TI  - Interactions of Isw2 chromatin remodeling complex with nucleosomal arrays:
      analyses using recombinant yeast histones and immobilized templates.
AB  - To facilitate the biochemical characterization of chromatin-associated proteins
      in the budding yeast Saccharomyces cerevisiae, we have developed a system to
      assemble nucleosomal arrays on immobilized templates using recombinant yeast core
      histones. This system enabled us to analyze the interaction of Isw2 ATP-dependent
      chromatin remodeling complex with nucleosomal arrays. We found that Isw2 complex
      interacts efficiently with both naked DNA and nucleosomal arrays in an ATP
      independent manner, suggesting that ATP is required at steps subsequent to this
      physical interaction. We identified the second subunit of Isw2 complex, encoded
      by open reading frame YGL 133w (herein named ITC1), and found that both subunits
      of the complex, Isw2p and Itc1p, are essential for efficient interaction with DNA
      and nucleosomal arrays. Both subunits are also required for nucleosome-stimulated
      ATPase activity and chromatin remodeling activity of the complex. Finally, we
      found that ITC1 is essential for function of Isw2 complex in vivo, since isw2 and
      itc1 deletion mutants exhibit virtually identical phenotypes. These results
      demonstrate the utility of our in vitro system in studying interactions between
      chromatin-associated proteins and nucleosomal arrays.

PMID- 11238945
TI  - Ras binding triggers ubiquitination of the Ras exchange factor Ras-GRF2.
AB  - Ras is a small GTPase that is activated by upstream guanine nucleotide exchange
      factors, one of which is Ras-GRF2. GRF2 is a widely expressed protein with
      several recognizable sequence motifs, including a Ras exchanger motif (REM), a
      PEST region containing a destruction box (DB), and a Cdc25 domain. The Cdc25
      domain possesses guanine nucleotide exchange factor activity and interacts with
      Ras. Herein we examine if the DB motif in GRF2 results in proteolysis via the
      ubiquitin pathway. Based on the solved structure of the REM and Cdc25 regions of
      the Son-of-sevenless (Sos) protein, the REM may stabilize the Cdc25 domain during
      Ras binding. The DB motif of GRF2 is situated between the REM and the Cdc25
      domains, tempting speculation that it may be exposed to ubiquitination machinery
      upon Ras binding. GRF2 protein levels decrease dramatically upon activation of
      GRF2, and dominant-negative Ras induces degradation of GRF2, demonstrating that
      signaling downstream of Ras is not required for the destruction of GRF2 and that
      binding to Ras is important for degradation. GRF2 is ubiquitinated in vivo, and
      this can be detected using mass spectrometry. In the presence of proteasome
      inhibitors, Ras-GRF2 accumulates as a high-molecular-weight conjugate, suggesting
      that GRF2 is destroyed by the 26S proteasome. Deleting the DB reduces the
      ubiquitination of GRF2. GRF2 lacking the Cdc25 domain is not ubiquitinated,
      suggesting that a protein that cannot bind Ras cannot be properly targeted for
      destruction. Point mutations within the Cdc25 domain that eliminate Ras binding
      also eliminate ubiquitination, demonstrating that binding to Ras is necessary for
      ubiquitination of GRF2. We conclude that conformational changes induced by GTPase
      binding expose the DB and thereby target GRF2 for destruction.

PMID- 11238946
TI  - beta(3)A-integrin downregulates the urokinase-type plasminogen activator receptor
      (u-PAR) through a PEA3/ets transcriptional silencing element in the u-PAR
      promoter.
AB  - Migration of cells requires interactions with the extracellular matrix mediated,
      in part, by integrins, proteases, and their receptors. Previous studies have
      shown that beta(3)-integrin interacts with the urokinase-type plasminogen
      activator receptor (u-PAR) at the cell surface. Since integrins mediate signaling
      into the cell, the current study was undertaken to determine if in addition
      beta(3)-integrin regulates u-PAR expression. Overexpression of beta(3)-integrin
      in CHO cells, which are avid expressers of the receptor, downregulated u-PAR
      protein and mRNA expression. The u-PAR promoter (-1,469 bp) that is normally
      constitutively active in CHO cells was downregulated by induced beta(3)-integrin
      expression. A region between -398 and -197 bp of the u-PAR promoter was critical
      for beta(3)-integrin-induced downregulation of u-PAR promoter activity. Deletion
      of the PEA3/ets motif at -248 bp substantially impaired the ability of beta(3)
      integrin to downregulate the u-PAR promoter, suggesting that the PEA3/ets site
      acts as a silencing element. An expression vector encoding the transcription
      factor PEA3 caused inhibition of the wild-type but not the PEA3/ets-deleted u-PAR
      promoter. The PEA3/ets site bound nuclear factors from CHO cells specifically,
      but binding was enhanced when beta(3)-integrin was overexpressed. A PEA3 antibody
      inhibited DNA-protein complex formation, indicating the presence of PEA3.
      Downregulation of the u-PAR promoter was achieved by the beta(3)A-integrin
      isoform but not by other beta(3)-integrin isoforms and required the cytoplasmic
      membrane NITY(759) motif. Moreover, overexpression of the short but not the long
      isoform of the beta(3)-integrin adapter protein beta(3)-endonexin blocked u-PAR
      promoter activity through the PEA3/ets binding site. Thus, besides the physical
      interaction of beta(3)-integrin and u-PAR at the cell surface, beta(3) signaling
      is implicated in the regulation of u-PAR gene transcription, suggesting a mutual
      regulation of adhesion and proteolysis receptors.

PMID- 11238947
TI  - RNA trafficking signals in human immunodeficiency virus type 1.
AB  - Intracellular trafficking of retroviral RNAs is a potential mechanism to target
      viral gene expression to specific regions of infected cells. Here we show that
      the human immunodeficiency virus type 1 (HIV-1) genome contains two sequences
      similar to the hnRNP A2 response element (A2RE), a cis-acting RNA trafficking
      sequence that binds to the trans-acting trafficking factor, hnRNP A2, and
      mediates a specific RNA trafficking pathway characterized extensively in
      oligodendrocytes. The two HIV-1 sequences, designated A2RE-1, within the major
      homology region of the gag gene, and A2RE-2, in a region of overlap between the
      vpr and tat genes, both bind to hnRNP A2 in vitro and are necessary and
      sufficient for RNA transport in oligodendrocytes in vivo. A single base change
      (A8G) in either sequence reduces hnRNP A2 binding and, in the case of A2RE-2,
      inhibits RNA transport. A2RE-mediated RNA transport is microtubule and hnRNP A2
      dependent. Differentially labelled gag and vpr RNAs, containing A2RE-1 and A2RE
      2, respectively, coassemble into the same RNA trafficking granules and are
      cotransported to the periphery of the cell. tat RNA, although it contains A2RE-2,
      is not transported as efficiently as vpr RNA. An A2RE/hnRNP A2-mediated
      trafficking pathway for HIV RNA is proposed, and the role of RNA trafficking in
      targeting HIV gene expression is discussed.

PMID- 11238949
TI  - Interaction with protein phosphatase 1 Is essential for bifocal function during
      the morphogenesis of the Drosophila compound eye.
AB  - The gene bifocal (bif), required for photoreceptor morphogenesis in the
      Drosophila compound eye, encodes a protein that is shown to interact with protein
      phosphatase 1 (PP1) using the yeast two-hybrid system. Complex formation between
      Bif and PP1 is supported by coprecipitation of the two proteins. Residues 992 to
      995 (RVQF) in the carboxy-terminal region of Bif, which conform to the consensus
      PP1-binding motif, are shown to be essential for the interaction of Bif with PP1.
      The interaction of PP1 with bacterially expressed and endogenous Bif can be
      disrupted by a synthetic peptide known to block interaction of other regulatory
      subunits with PP1. Null bif mutants exhibit a rough eye phenotype, disorganized
      rhabdomeres (light-gathering rhodopsin-rich microvillar membrane structures in
      the photoreceptor cells) and alterations in the actin cytoskeleton. Expression of
      wild-type bif transgenes resulted in significant rescue of these abnormalities.
      In contrast, expression of transgenes encoding the Bif F995A mutant, which
      disrupts binding to PP1, was unable to rescue any aspect of the bif phenotype.
      The results indicate that the PP1-Bif interaction is critical for the rescue and
      that a major function of Bif is to target PP1c to a specific subcellular
      location. The role of the PP1-Bif complex in modulating the organization of the
      actin cytoskeleton underlying the rhabdomeres is discussed.

PMID- 11238948
TI  - Dual inactivation of RB and p53 pathways in RAS-induced melanomas.
AB  - The frequent loss of both INK4a and ARF in melanoma raises the question of which
      INK4a-ARF gene product functions to suppress melanoma genesis in vivo. Moreover,
      the high incidence of INK4a-ARF inactivation in transformed melanocytes, along
      with the lack of p53 mutation, implies a cell type-specific role for INK4a-ARF
      that may not be complemented by other lesions of the RB and p53 pathways. A mouse
      model of cutaneous melanoma has been generated previously through the combined
      effects of INK4a(Delta2/3) deficiency (null for INK4a and ARF) and melanocyte
      specific expression of activated RAS (tyrosinase-driven H-RAS(V12G), Tyr-RAS). In
      this study, we made use of this Tyr-RAS allele to determine whether activated RAS
      can cooperate with p53 loss in melanoma genesis, whether such melanomas are
      biologically comparable to those arising in INK4a(Delta2/3-/-) mice, and whether
      tumor-associated mutations emerge in the p16(INK4a)-RB pathway in such melanomas.
      Here, we report that p53 inactivation can cooperate with activated RAS to promote
      the development of cutaneous melanomas that are clinically indistinguishable from
      those arisen on the INK4a(Delta2/3) null background. Genomewide analysis of RAS
      induced p53 mutant melanomas by comparative genomic hybridization and candidate
      gene surveys revealed alterations of key components governing RB-regulated G(1)/S
      transition, including c-Myc, cyclin D1, cdc25a, and p21(CIP1). Consistent with
      the profile of c-Myc dysregulation, the reintroduction of p16(INK4a) profoundly
      reduced the growth of Tyr-RAS INK4a(Delta2/3-/-) tumor cells but had no effect on
      tumor cells derived from Tyr-RAS p53(-/-) melanomas. Together, these data
      validate a role for p53 inactivation in melanomagenesis and suggest that both the
      RB and p53 pathways function to suppress melanocyte transformation in vivo in the
      mouse.

PMID- 11238950
TI  - Involvement of IQGAP1, an effector of Rac1 and Cdc42 GTPases, in cell-cell
      dissociation during cell scattering.
AB  - We have previously proposed that IQGAP1, an effector of Rac1 and Cdc42,
      negatively regulates cadherin-mediated cell-cell adhesion by interacting with
      beta-catenin and by causing the dissociation of alpha-catenin from cadherin-beta
      catenin-alpha-catenin complexes and that activated Rac1 and Cdc42 positively
      regulate cadherin-mediated cell-cell adhesion by inhibiting the interaction of
      IQGAP1 with beta-catenin. However, it remains to be clarified in which
      physiological processes the Rac1-Cdc42-IQGAP1 system is involved. We here
      examined whether the Rac1-IQGAP1 system is involved in the cell-cell dissociation
      of Madin-Darby canine kidney II cells during 12-O-tetradecanoylphorbol-13-acetate
      (TPA)- or hepatocyte growth factor (HGF)-induced cell scattering. By using
      enhanced green fluorescent protein (EGFP)-tagged alpha-catenin, we found that
      EGFP-alpha-catenin decreased prior to cell-cell dissociation during cell
      scattering. We also found that the Rac1-GTP level decreased after stimulation
      with TPA and that the Rac1-IQGAP1 complexes decreased, while the IQGAP1-beta
      catenin complexes increased during action of TPA. Constitutively active Rac1 and
      IQGAP1 carboxyl terminus, a putative dominant-negative mutant of IQGAP1,
      inhibited the disappearance of alpha-catenin from sites of cell-cell contact
      induced by TPA. Taken together, these results indicate that alpha-catenin is
      delocalized from cell-cell contact sites prior to cell-cell dissociation induced
      by TPA or HGF and suggest that the Rac1-IQGAP1 system is involved in cell-cell
      dissociation through alpha-catenin relocalization.

PMID- 11238951
TI  - Distinct functional domains of nibrin mediate Mre11 binding, focus formation, and
      nuclear localization.
AB  - The inherited chromosomal instability disorder Nijmegen breakage syndrome (NBS)
      results from truncating mutations in the NBS1 gene, which encodes the protein
      nibrin. Nibrin is part of a nuclear multiprotein complex that also contains the
      DNA repair proteins Mre11 and Rad50. Upon irradiation, this complex redistributes
      within the nucleus, forming distinct foci that have been implicated as sites of
      DNA repair. In NBS cells, nibrin is absent and Mre11 and Rad50 are cytoplasmic.
      In this study, the interacting domains on nibrin and Mre11 were mapped using the
      yeast two-hybrid system and expression of epitope-tagged constructs in NBS
      fibroblasts. Deletion of the carboxy-terminal 101 amino acids of nibrin
      eliminated its ability to interact with Mre11 and to complement the radiation
      sensitivity of NBS cells. However, this truncated form of nibrin could localize
      to the nucleus and form radiation-inducible foci. Expression of a carboxy
      terminal 354-amino-acid fragment of nibrin was sufficient to direct the nuclear
      localization of nibrin, as well as that of Mre11 and Rad50. Despite providing
      some partial complementation of the radiation-sensitive phenotype, the nibrin
      Mre11-Rad50 complexes in these cells were unable to form foci. These results
      indicate that nibrin directs not only the nuclear localization of the nibrin
      Mre11-Rad50 complexes but also radiation-induced focus formation. However, direct
      interaction between nibrin and Mre11 is required for normal cellular survival
      postirradiation. Distinct domains of nibrin are required for each of these
      functions, focus formation, nuclear localization, and Mre11 interaction.

PMID- 11238952
TI  - ATF4 degradation relies on a phosphorylation-dependent interaction with the
      SCF(betaTrCP) ubiquitin ligase.
AB  - The ubiquitin-proteasome pathway regulates gene expression through protein
      degradation. Here we show that the F-box protein betaTrCP, the receptor component
      of the SCF E3 ubiquitin ligase responsible for IkappaBalpha and beta-catenin
      degradation, is colocalized in the nucleus with ATF4, a member of the ATF-CREB
      bZIP family of transcription factors, and controls its stability. Association
      between the two proteins depends on ATF4 phosphorylation and on ATF4 serine
      residue 219 present in the context of DSGXXXS, which is similar but not identical
      to the motif found in other substrates of betaTrCP. ATF4 ubiquitination in HeLa
      cells is enhanced in the presence of betaTrCP. The F-box-deleted betaTrCP protein
      behaves as a negative transdominant mutant that inhibits ATF4 ubiquitination and
      degradation and, subsequently, enhances its activity in cyclic AMP-mediated
      transcription. ATF4 represents a novel substrate for the SCF(betaTrCP) complex,
      which is the first mammalian E3 ubiquitin ligase identified so far for the
      control of the degradation of a bZIP transcription factor.

PMID- 11238953
TI  - Activation of Akt (protein kinase B) in mammary epithelium provides a critical
      cell survival signal required for tumor progression.
AB  - Activation of Akt by the phosphatidylinositol 3'-OH kinase (PI3K) results in the
      inhibition of proapoptotic signals and the promotion of survival signals (L. P.
      Kane et al., Curr. Biol. 9:601-604, 1999; G. J. Kops et al., Nature 398:630-634,
      1999). Evidence supporting the importance of the PI3K/Akt signaling pathway in
      tumorigenesis stems from experiments with transgenic mice bearing polyomavirus
      middle T antigen under the control of the mouse mammary tumor virus long terminal
      repeat promoter. Mammary epithelium-specific expression of polyomavirus middle T
      antigen results in the rapid development of multifocal metastatic mammary tumors,
      whereas transgenic mice expressing a mutant middle T antigen decoupled from the
      phosphatidylinositol 3'-OH kinase (MTY315/322F) develop extensive mammary gland
      hyperplasias that are highly apoptotic. To directly assess the role of Akt in
      mammary epithelial development and tumorigenesis, we generated transgenic mice
      expressing constitutively active Akt (HAPKB308D473D or Akt-DD). Although
      expression of Akt-DD interferes with normal mammary gland involution, tumors were
      not observed in these strains. However, coexpression of Akt-DD with MTY315/322F
      resulted in a dramatic acceleration of mammary tumorigenesis correlated with
      reduced apoptotic cell death. Furthermore, coexpression of Akt-DD with
      MTY315/322F resulted in phosphorylation of the FKHR forkhead transcription factor
      and translational upregulation of cyclin D1 levels. Importantly, we did not
      observe an associated restoration of wild-type metastasis levels in the
      bitransgenic strain. Taken together these observations indicate that activation
      of Akt can contribute to tumor progression by providing an important cell
      survival signal but does not promote metastatic progression.

PMID- 11238954
TI  - Disruption of the mouse mu-calpain gene reveals an essential role in platelet
      function.
AB  - Conventional calpains are ubiquitous calcium-regulated cysteine proteases that
      have been implicated in cytoskeletal organization, cell proliferation, apoptosis,
      cell motility, and hemostasis. There are two forms of conventional calpains: the
      mu-calpain, or calpain I, which requires micromolar calcium for half-maximal
      activation, and the m-calpain, or calpain II, which functions at millimolar
      calcium concentrations. We evaluated the functional role of the 80-kDa catalytic
      subunit of mu-calpain by genetic inactivation using homologous recombination in
      embryonic stem cells. The mu-calpain-deficient mice are viable and fertile. The
      complete deficiency of mu-calpain causes significant reduction in platelet
      aggregation and clot retraction but surprisingly the mutant mice display normal
      bleeding times. No detectable differences were observed in the cleavage pattern
      and kinetics of calpain substrates such as the beta3 subunit of alphaIIbbeta3
      integrin, talin, and ABP-280 (filamin). However, mu-calpain null platelets
      exhibit impaired tyrosine phosphorylation of several proteins including the beta3
      subunit of alphaIIbbeta3 integrin, correlating with the agonist-induced reduction
      in platelet aggregation. These results provide the first direct evidence that mu
      calpain is essential for normal platelet function, not by affecting the cleavage
      of cytoskeletal proteins but by potentially regulating the state of tyrosine
      phosphorylation of the platelet proteins.

PMID- 11238955
TI  - Functional phosphorylation sites in the C-terminal region of the multivalent
      multifunctional transcriptional factor CTCF.
AB  - CTCF is a widely expressed and highly conserved multi-Zn-finger (ZF) nuclear
      factor. Binding to various CTCF target sites (CTSs) is mediated by combinatorial
      contributions of different ZFs. Different CTSs mediate distinct CTCF functions in
      transcriptional regulation, including promoter repression or activation and
      hormone-responsive gene silencing. In addition, the necessary and sufficient core
      sequences of diverse enhancer-blocking (insulator) elements, including CpG
      methylation-sensitive ones, have recently been pinpointed to CTSs. To determine
      whether a posttranslational modification may modulate CTCF functions, we studied
      CTCF phosphorylation. We demonstrated that most of the modifications that occur
      at the carboxy terminus in vivo can be reproduced in vitro with casein kinase II
      (CKII). Major modification sites map to four serines within the
      S(604)KKEDS(609)S(610)DS(612)E motif that is highly conserved in vertebrates.
      Specific mutations of these serines abrogate phosphorylation of CTCF in vivo and
      CKII-induced phosphorylation in vitro. In addition, we showed that completely
      preventing phosphorylation by substituting all serines within this site resulted
      in markedly enhanced repression of the CTS-bearing vertebrate c-myc promoters,
      but did not alter CTCF nuclear localization or in vitro DNA-binding
      characteristics assayed with c-myc CTSs. Moreover, these substitutions manifested
      a profound effect on negative cell growth regulation by wild-type CTCF. CKII may
      thus be responsible for attenuation of CTCF activity, either acting on its own or
      by providing the signal for phosphorylation by other kinases and for CTCF
      interacting protein partners.

PMID- 11238956
TI  - A novel mitogen-activated protein kinase is responsive to Raf and mediates growth
      factor specificity.
AB  - The proto-oncogene Raf is a major regulator of growth and differentiation.
      Previous studies from a number of laboratories indicate that Raf activates a
      signaling pathway that is independent of the classic MEK1,2-ERK1,2 cascade.
      However, no other signaling cascade downstream of Raf has been identified. We
      describe a new member of the mitogen-activated protein kinase family, p97, an
      ERK5-related kinase that is activated and Raf associated when cells are
      stimulated by Raf. Furthermore, p97 is selectively responsive to different growth
      factors, providing a mechanism for specificity in cellular signaling. Thus, p97
      is activated by the neurogenic factor fibroblast growth factor (FGF) but not the
      mitogenic factor epidermal growth factor (EGF) in neuronal cells. Conversely, the
      related kinase ERK5 is activated by EGF but not FGF. p97 phosphorylates
      transcription factors such as Elk-1 and Ets-2 but not MEF2C at transactivating
      sites, whereas ERK5 phosphorylates MEF2C but not Elk-1 or Ets-2. Finally, p97 is
      expressed in a number of cell types including primary neural and NIH 3T3 cells.
      Taken together, these results identify a new signaling pathway that is distinct
      from the classic Raf-MEK1,2-ERK1,2 kinase cascade and can be selectively
      stimulated by growth factors that produce discrete biological outcomes.

PMID- 11238957
TI  - A new chlamydia-like 16S rDNA sequence from a clinical sample.

PMID- 11238958
TI  - Bacterial cell division protein FtsZ is a specific substrate for the AAA family
      protease FtsH.

PMID- 11238959
TI  - Bacterial chromosome segregation.
AB  - Recent years have witnessed a resurgence of interest in how the bacterial
      chromosome is organized and how newly replicated chromosomes are faithfully
      segregated into daughter cells on cell division. In the past, the problem with
      studying bacterial chromosomes was their lack of any obvious morphology, combined
      with the lack of ability to readily separate DNA replication and segregation
      functions into distinct stages like those observed in eukaryotic cells. This was
      due to the overlapping nature of these events in most bacterial systems used in
      the laboratory. The situation has now changed as new tools have become available
      that enable chromosomes and specific chromosomal sites to be labelled and
      monitored throughout the cell cycle, and this has led to rapid progress and the
      discovery of many unexpected results. Historically, chromosome segregation was
      thought to be achieved through passive processes where chromosomes were separated
      through some kind of membrane/cell wall attachment and were moved apart as the
      cell grew (Jacob et al., 1963). We now know that this is not the case and that
      there are specific mechanisms to actively partition chromosomes. This review will
      focus principally on the Gram-positive sporulating bacterium Bacillus subtilis,
      but will also cover work carried out on Escherichia coli, in which valuable
      information has been obtained, and will cover the events that occur on
      termination of chromosome replication, chromosome decatenation and chromosome
      separation.

PMID- 11238960
TI  - Phenotypic consequences of red-white colony type variation in Mycobacterium
      avium.
AB  - Mycobacterium avium undergoes reversible morphotypic switching between the
      virulent transparent colony type and the less virulent opaque colony type. A new
      morphotypic switch in M. avium, termed red-white, that becomes visible when
      opaque colonies of clinical isolates are grown on agar media containing Congo
      red, was recently described. White opaque (WO) variants were found to be more
      resistant to multiple antibiotics than were red opaque (RO) variants. The present
      paper reports that transparent derivatives of RO and WO clones retain the
      differential Congo red binding properties of their opaque parents, indicating
      that the opaque-transparent switch operates independently of the red-white
      switch. White transparent variants were more resistant to clarithromycin and
      rifampin in vitro, and better able to survive within human macrophages, than
      their red transparent counterparts. Neither red nor white variants were markedly
      favoured during growth in vitro; however, red variants were better able to spread
      on soft agar (sliding motility), a potential selective advantage under some
      environmental circumstances. White-to-red switching was frequently observed in
      vitro and was accompanied by decreased antibiotic resistance and increased
      motility. Red-to-white switching has yet to be observed in vitro, indicating that
      the red morphotype is very stable. Significantly, some widely studied laboratory
      reference strains of M. avium, including strain 2151 and the genome sequence
      strain 104, are stable red clones. These strains are intrinsically antibiotic
      resistant and virulent in animal models, but they may not express genes encoding
      the elevated levels of antibiotic resistance and intracellular survival observed
      in white variants.

PMID- 11238961
TI  - Regulation of the switch from early to late bacteriophage lambda DNA replication.
AB  - There are two modes of bacteriophage lambda DNA replication following infection
      of its host, Escherichia coli. Early after infection, replication occurs
      according to the theta (theta or circle-to-circle) mode, and is later switched to
      the sigma (sigma or rolling-circle) mode. It is not known how this switch,
      occurring at a specific time in the infection cycle, is regulated. Here it is
      demonstrated that in wild-type cells the replication starting from orilambda
      proceeds both bidirectionally and unidirectionally, whereas in bacteria devoid of
      a functional DnaA protein, replication from orilambda is predominantly
      unidirectional. The regulation of directionality of replication from orilambda is
      mediated by positive control of lambda p(R) promoter activity by DnaA, since the
      mode of replication of an artificial lambda replicon bearing the p(tet) promoter
      instead of p(R) was found to be independent of DnaA function. These findings and
      results of density-shift experiments suggest that in dnaA mutants infected with
      lambda, phage DNA replication proceeds predominantly according to the
      unidirectional theta mechanism and is switched early after infection to the sigma
      mode. It is proposed that in wild-type E. coli cells infected with lambda, phage
      DNA replication proceeds according to a bidirectional theta mechanism early after
      infection due to efficient transcriptional activation of orilambda, stimulated by
      the host DnaA protein. After a few rounds of this type of replication, the
      resulting increased copy number of lambda genomic DNA may cause a depletion of
      free DnaA protein because of its interaction with the multiple DnaA-binding sites
      in lambda DNA. It is proposed that this may lead to inefficient transcriptional
      activation of orilambda resulting in unidirectional theta replication followed by
      sigma type replication.

PMID- 11238962
TI  - A unipolarly located, cell-surface-associated agglutinin, RapA, belongs to a
      family of Rhizobium-adhering proteins (Rap) in Rhizobium leguminosarum bv.
      trifolii.
AB  - The phage-display cloning technique was used to find rhizobial proteins that bind
      to receptors located on the bacterial cell surface. The aim was to clone the
      gene(s) encoding rhicadhesin, a universal rhizobial adhesion protein, and/or
      other cell-surface-binding proteins. Four such Rhizobium-adhering proteins (Rap)
      were revealed in Rhizobium leguminosarum bv. trifolii strain R200. The binding is
      mediated by homologous Ra domains in these proteins. One member of the Rap
      protein family, named RapA1, is a secreted calcium-binding protein, which are
      also properties expected for rhicadhesin. However, the size of the protein (24
      kDa instead of 14 kDa) and its distribution among different rhizobia (present in
      only Rhizobium leguminosarum biovars and R. etli instead of all members of
      Rhizobiaceae argue against RapA1 being rhicadhesin. Protein RapA1 consists of two
      homologous Ra domains and agglutinates R200 cells by binding to specific
      receptors located at one cell pole during exponential growth. Expression of these
      cell-surface receptors was detected only in rhizobia that produce the RapA
      proteins. The authors propose that the homologous Ra domains, found to be present
      also in other proteins with different structure, represent lectin domains, which
      confer upon these proteins the ability to recognize their cognate carbohydrate
      structures.

PMID- 11238964
TI  - An immunodominant membrane protein gene from the Western X-disease phytoplasma is
      distinct from those of other phytoplasmas.
AB  - Membrane proteins mediate several important processes, including attachment, in
      several Mollicute species. Phytoplasmas are non-culturable plant pathogenic
      mollicutes that are transmitted in a specific manner by certain phloem-feeding
      insect vectors. Because it is likely that phytoplasma membrane proteins are
      involved with some aspect of the transmission process, their identification,
      isolation and characterization are important first steps in understanding
      phytoplasma transmission. A 32 kDa immunodominant protein (IDP) from the Western
      X-disease (WX) phytoplasma was purified from infected plants by
      immunoprecipitation using monoclonal antibodies, and two peptides from a tryptic
      digest were sequenced. PCR primers designed from these sequences amplified a 145
      bp product which hybridized with WX-related phytoplasmas in Southern blots. This
      PCR product was used to identify a 2.5 kbp ECO:RI-HIN:dIII fragment that was
      cloned and sequenced. A complete 864 bp ORF (idpA) was identified for which the
      putative translation product contained both of the tryptic digest peptide
      sequences that were used to design the PCR primers. Analysis of the predicted
      IdpA sequence indicated two transmembrane domains but no cleavage point. The
      amino acid sequence had no significant homology with other known phytoplasma IDP
      genes. The idpA ORF was cloned into an Escherichia coli expression vector and a
      fusion protein of the predicted size was identified in Western blots using a WX
      specific antiserum. A rabbit polyclonal antiserum was prepared to the purified
      expression protein and this reacted with both the E. coli-expressed and native WX
      phytoplasma proteins. This newly identified WX IDP (IdpA) is distinct from other
      known mollicute membrane proteins.

PMID- 11238963
TI  - NAD(P)H:menadione oxidoreductase of the amitochondriate eukaryote Giardia
      lamblia: a simpler homologue of the vertebrate enzyme.
AB  - The amitochondriate eukaryote Giardia lamblia contains an NAD(P)H:menadione
      oxidoreductase (EC 1.6.99.2) (glQR) that catalyses the two-electron transfer
      oxidation of NAD(P)H with a quinone as acceptor. The gene encoding this protein
      in G. lamblia was expressed in Escherichia coli. The purified recombinant protein
      had an NAD(P)H oxidoreductase activity, with NADPH being a more efficient
      electron donor than NADH. Menadione, naphthoquinone and several artificial
      electron acceptors served as substrate for the enzyme. glQR shows high amino acid
      similarity to its homologues in vertebrates and also to a series of hypothetical
      proteins from bacteria. Although glQR is considerably smaller than the mammalian
      enzymes, three-dimensional modelling shows similar arrangement of the secondary
      structural elements. Most amino acid residues of the mammalian enzymes that
      participate in substrate binding or catalysis are conserved. Conservation of
      these features and the similarity in substrate specificity and in susceptibility
      to inhibitors establish glQR as an authentic member of this protein family.

PMID- 11238965
TI  - Development of a genetic system for the transfer of DNA into Flavobacterium
      heparinum.
AB  - Flavobacterium heparinum (now Pedobacter heparinus) is a Gram-negative soil
      bacterium which can produce yellow pigments. It synthesizes five enzymes that
      degrade glycosoaminoglycan molecules. The study of this unique bacterium has been
      limited by the absence of a genetic manipulation system. In this paper, the
      construction of a conjugation/integration plasmid system and a broad-host-range
      plasmid, both of which contain a F. heparinum functional selective marker created
      by placing the trimethoprim resistance gene, dhfrII, under the control of the
      hepA regulatory region is described. Both plasmids were introduced into F.
      heparinum by conjugation and/or electroporation, and trimethoprim resistant
      colonies were obtained. Fifty electroporants were obtained per microgram
      covalently closed circular plasmid DNA. The existence of integrated plasmid DNA
      was confirmed by Southern hybridization and PCR. The existence of a derivative of
      the broad-host-range plasmid pBBR1 in F. heparinum was demonstrated by plasmid
      digestion and Southern hybridization, and by transformation of Escherichia coli.

PMID- 11238966
TI  - A role for DNA supercoiling in the regulation of the cytochrome bd oxidase of
      Escherichia coli.
AB  - The cydAB operon of Escherichia coli encodes cytochrome bd, a terminal oxidase in
      the aerobic respiratory chain. The high oxygen affinity of this oxidase explains
      its increased synthesis under low-oxygen conditions. Expression of the cydAB
      operon is controlled by the ArcA/ArcB two-component system and the oxygen-sensing
      transcriptional regulator Fnr. However, cydAB expression is still induced upon
      entry into stationary phase or following a shift to anaerobic conditions in a
      mutant deleted for arcA and fnr [Cotter, P. A. & Gunsalus, R. P. (1992), FEMS
      Microbiol Lett 91, 31-36]. Indeed, such a mutant contains 60% of the wild-type
      levels of spectrally detectable cytochrome bd. A possible mechanism to account
      for this regulation is that changes in negative supercoiling, which occur during
      a shift to low-oxygen or anaerobic conditions, may contribute to the regulation
      of the cydAB operon. This paper reports several lines of evidence in support of
      this idea. Firstly, the expression of cydAB, and the final level of spectrally
      detectable cytochrome bd, is sensitive to inhibitors of DNA gyrase, the enzyme
      responsible for introducing negative supercoils into DNA. Both nalidixic acid and
      novobiocin reduce cydA-lacZ expression in a concentration-dependent manner.
      Secondly, in a gyrA mutant, defective in DNA gyrase activity, expression of cydAB
      is reduced to a basal level that is no longer sensitive to the oxygen status.
      Both gyrase inhibitors and the gyrA mutation reduce cydAB expression in a strain
      deleted for arcA and fnr, indicating that their effects are not mediated
      indirectly through ArcA or Fnr, but rather that they are likely to be direct
      effects on cydAB expression. In conclusion, the authors have shown that changes
      in DNA supercoiling play a role in the induction of cydAB expression and may
      provide a general way of increasing cytochrome bd levels in the cell in response
      to environmental stress.

PMID- 11238967
TI  - Molecular evolution of the GDP-mannose pathway genes (manB and manC) in
      Salmonella enterica.
AB  - The evolutionary history of the GDP-mannose pathway in Salmonella enterica was
      studied via sequencing manB and manC genes from 13 representative strains for O
      antigens containing mannose and/or sugar derivatives of GDP-D-mannose. In
      addition, colanic acid (CA) manB and manC genes were sequenced from selected
      strains, as the basis for a detailed comparison. Interestingly, including the
      eight previously characterized O antigen gene clusters, 12 of the 21 S. enterica
      strains studied in total (each representing a different O antigen structure)
      possess a manB gene which displays DNA identity, ranging from 93 to 99%, to the
      CA manB gene of S. enterica LT2. Furthermore, the CA-like manB genes (as well as
      the CA manB and manC genes) display subspecies specificity, and the CA and CA
      like manB genes (for individual strains) appear to be evolving in concert via
      gene conversion events. In comparison, the manC genes were generally not CA-like,
      a situation also apparent in Escherichia coli,and therefore most strongly
      reflected the evolutionary history of the S. enterica O antigen GDP-mannose
      pathway. It appears that, in relatively recent times, gene capture from a distant
      source has occurred infrequently, and that groups of manB and manC genes have
      been maintained and are continuing to evolve within S. enterica and more closely
      related species.

PMID- 11238968
TI  - Sequence variation in dichloromethane dehalogenases/glutathione S-transferases.
AB  - Dichloromethane dehalogenase/glutathione S-transferase allows methylotrophic
      bacteria to grow with dichloromethane (DCM), a predominantly man-made compound.
      Bacteria growing with DCM by virtue of this enzyme have been readily isolated in
      the past. So far, the sequence of the dcmA gene encoding DCM dehalogenase has
      been determined for Methylobacterium dichloromethanicum DM4 and Methylophilus sp.
      DM11. DCM dehalogenase genes closely related to that of strain DM4 were amplified
      by PCR and cloned from total DNA from 14 different DCM-degrading strains,
      enrichment cultures and sludge samples from wastewater treatment plants. In
      total, eight different sequences encoding seven different protein sequences were
      obtained. Sequences of different origin were identical in several instances.
      Sequence variation was limited to base substitutions; strikingly, 16 of the 19
      substitutions in the dcmA gene itself encoded amino acids that were different
      from those of the DM4 sequence. The kinetic parameters k(cat) and K:(m), the pH
      optimum and the stability of representative DCM dehalogenase variants were
      investigated, revealing minor differences between the properties of DCM
      dehalogenases related to that from strain DM4.

PMID- 11238969
TI  - The binding pattern of two carbohydrate-binding modules of laminarinase Lam16A
      from Thermotoga neapolitana: differences in beta-glucan binding within family
      CBM4.
AB  - Carbohydrate-binding modules (CBMs) are often part of the complex hydrolytic
      extracellular enzymes from bacteria and may modulate their catalytic activity.
      The thermostable catalytic domain of laminarinase Lam16A from Thermotoga
      neapolitana (glycosyl hydrolase family 16) is flanked by two CBMs, 148 and 161 aa
      long. They share a sequence identity of 30%, are homologous to family CBM4 and
      are thus called CBM4-1 and CBM4-2 respectively. Recombinant Lam16A proteins
      deleted for one or both binding modules and the isolated module CBM4-1 were
      characterized. Proteins containing the N-terminal module CBM4-1 bound to the
      soluble polysaccharides laminarin (1,3-beta-glucan) and barley 1,3/1,4-beta
      glucan, and proteins containing the C-terminal module CBM4-2 bound additionally
      to curdlan (1,3-beta-glucan) and pustulan (1,6-beta-glucan), and to insoluble
      yeast cell wall beta-glucan. The activity of the catalytic domain on soluble 1,3
      beta-glucans was stimulated by the presence of CBM4-1, whereas the presence of
      CBM4-2 enhanced the Lam16A activity towards gelatinized and insoluble or mixed
      linkage 1,3-beta-glucan. Thermostability of the catalytic domain was not affected
      by the truncations. Members of family CBM4 can be divided into four subfamilies,
      members of which show different polysaccharide-binding specificities
      corresponding to the catalytic specificities of the associated hydrolytic
      domains.

PMID- 11238970
TI  - A multifunctional polyketide-peptide synthetase essential for albicidin
      biosynthesis in Xanthomonas albilineans.
AB  - Albicidins, a family of potent antibiotics and phytotoxins produced by the
      sugarcane leaf scald pathogen Xanthomonas albilineans, inhibit DNA replication in
      bacteria and plastids. A gene located by Tn5-tagging was confirmed by
      complementation to participate in albicidin biosynthesis. The gene (xabB) encodes
      a large protein (predicted M:(r) 525695), with a modular architecture indicative
      of a multifunctional polyketide synthase (PKS) linked to a non-ribosomal peptide
      synthetase (NRPS). At 4801 amino acids in length, XabB is the largest reported
      PKS-NRPS. Twelve catalytic domains in this multifunctional enzyme are arranged in
      the order N terminus-acyl-CoA ligase (AL)-acyl carrier protein (ACP)-beta
      ketoacyl synthase (KS)-beta-ketoacyl reductase (KR)-ACP-ACP-KS-peptidyl carrier
      protein (PCP)-condensation (C)-adenylation-PCP-C. The modular architecture of
      XabB indicates likely steps in albicidin biosynthesis and approaches to enhance
      antibiotic yield. The novel pattern of domains, in comparison with known PKS-NRPS
      enzymes for antibiotic production, also contributes to the knowledge base for
      rational design of enzymes producing novel antibiotics.

PMID- 11238971
TI  - Plantaricin W from Lactobacillus plantarum belongs to a new family of two-peptide
      lantibiotics.
AB  - Plantaricin W (Plw) is a new two-peptide bacteriocin, from Lactobacillus
      plantarum, which inhibits a large number of Gram-positive bacteria. The two
      peptides, Plwalpha (comprising 29 residues) and Plwbeta (comprising 32 residues),
      were isolated from the culture supernatants and characterized. The individual
      peptides had low antimicrobial activity but acted synergistically, and synergism
      was seen at all mixing ratios tested. The data indicate that the two peptides
      work in a 1:1 ratio. Chemical analyses showed that both peptides are
      lantibiotics, but two unmodified cysteines and one serine residue were present in
      Plwalpha, and Plwbeta contained one cysteine residue. The Plw structural genes
      were sequenced and shown to encode prepeptides with sequence similarities to two
      other two-peptide lantibiotics, namely staphylococcin C55 and lacticin 3147. The
      conserved residues are mainly serines, threonines and cysteines that can be
      involved in intramolecular thioether bond formation in the C-terminal parts of
      the molecules. This indicates that these bacteriocins are members of a new family
      of lantibiotics with common bridging patterns, and that the ring structures play
      an important functional role. Based on the data a structural model is presented
      in which each peptide has a central lanthionine and two overlapping thioether
      bridges close to their C-termini.

PMID- 11238972
TI  - Characterization of a copper-transport operon, copYAZ, from Streptococcus mutans.
AB  - A copper-transport (copYAZ) operon was cloned from the oral bacterium
      Streptococcus mutans JH1005. DNA sequencing showed that the operon contained
      three genes (copY, copA and copZ), which were flanked by a single promoter and a
      factor-independent terminator. copY encoded a small protein of 147 aa with a
      heavy-metal-binding motif (CXCX(4)CXC) at the C-terminus. CopY shared extensive
      homology with other bacterial negative transcriptional regulators. copA encoded a
      742 aa protein that shared extensive homology with P-type ATPases. copZ encoded a
      67 aa protein that also contained a heavy-metal-binding motif (CXXC) at the N
      terminus. Northern blotting showed that a 3.2 kb transcript was produced by Cu2+
      induced Strep. mutans cells, suggesting that the genes were synthesized as a
      polycistronic message. The transcriptional start site of the cop operon was
      mapped and shown to lie within the inverted repeats of the promoter-operator
      region. Strep. mutans wild-type cells were resistant to 800 microM Cu2+, whereas
      cells of a cop knock-out mutant were killed by 200 microM Cu2+. Complementation
      of the cop knock-out mutant with the cop operon restored Cu2+ resistance to wild
      type level. The wild-type and the mutant did not show any differences in
      susceptibility to other heavy metals, suggesting that the operon was specific for
      copper. By using a chloramphenicol acetyltransferase reporter gene fusion, the
      cop operon was shown to be negatively regulated by CopY and could be derepressed
      by Cu2+.

PMID- 11238973
TI  - Supply of O2 regulates demand for O2 and uptake of malate by N2-fixing bacteroids
      from soybean nodules.
AB  - Bacteroids, prepared anaerobically from soybean root nodules by fractional
      centrifugation or by sucrose or Percoll density-gradient methods, were retained
      within a stirred, flow-through reaction chamber and used to determine rates of
      respiration and N2 fixation at various rates of O2 supply. Liquid reaction
      solutions containing malate, oxyleghaemoglobin, dissolved N2 and various levels
      of dissolved O2 were passed through the reaction chamber at measured rates of
      flow. The relative oxygenation of leghaemoglobin in the chamber was determined
      automatically by spectrophotometry of the effluent solution, and the
      concentrations of free, dissolved O2 ([O2(free)]) and the rates of O2 consumption
      were calculated. N2 fixation was measured by analysis of fractions of effluent.
      The principal finding was that stepwise increases in the flow rate (increasing
      the supply of O2 and malate) induced an increase in O2 demand (respiration)
      resulting in a decrease in [O2(free)] and increased N2 fixation. In some
      experiments, samples of bacteroids were withdrawn from the flow chamber during
      steady states and the rates of malate uptake were measured in standard,
      microaerobic assays. Progressive taking of samples from the flow chamber whilst
      maintaining constant flow rates (increasing the supply of O2 and malate per
      bacteroid) also resulted in increased O2 demand and declines in [O2(free)]. With
      increased bacteroid respiration, transport of malate into bacteroids (linear with
      time between 1 and 5 min after starting each assay) increased proportionally.
      This suggests that the rate of malate transport is tightly coupled with bacteroid
      respiration. Thus, bacteroid respiration, coupled with malate uptake, must be
      regulated by the rate of O2 supply, rather than by the [O2(free)] prevailing in
      the stirred chamber as found or assumed in previous work. These features are
      discussed in relation to N2 fixation by anaerobically isolated bacteroids.

PMID- 11238974
TI  - Contribution of the phosphoenolpyruvate:mannose phosphotransferase system to
      carbon catabolite repression in Lactobacillus pentosus.
AB  - The role of the Lactobacillus pentosus phosphoenolpyruvate:mannose
      phosphotransferase system (mannose PTS) in sugar transport and control of sugar
      utilization was investigated. Growth experiments and measurements of PEP
      dependent phosphorylation of sugars, of sugar transport and of catabolic enzyme
      activity were performed, to compare a wild-type strain with an EIIB(Man) mutant,
      LPE6, and a ccpA mutant, LPE4. Fructose uptake in wild-type bacteria demonstrated
      the presence of two fructose-specific PTSs: a high-affinity system, EII(Fru)
      (K:(m)=52 microM) which is inducible by fructose, and a low-affinity system
      (K:(m)=300 microM). The latter system was lacking in LPE6 and therefore
      corresponds to EII(Man). LPE6 was unable to phosphorylate glucose, mannose, N:
      acetylglucosamine and 2-deoxyglucose in a PEP-dependent reaction, indicating that
      these sugars are substrates of EII(Man). Transport and phosphorylation of these
      compounds was the same in LPE4 and in wild-type bacteria, although growth of LPE4
      on these sugars was impaired. In wild-type bacteria and in LPE4 the activity of
      EII(Fru) was lowered by the presence of EII(Man) substrates in the growth medium,
      but this decrease was not observed in LPE6. These results indicate that EII(Man)
      but not CcpA regulates the synthesis of EII(Fru). Mutations in EII(Man) or CcpA
      resulted in a relief of catabolite repression exerted by EII(Man) substrates on
      the activity of beta-galactosidase and beta-glucosidase, indicating that EII(Man)
      and CcpA are important components in catabolite repression in L. pentosus.
      Fructose-mediated repression of these two enzymes appeared to be correlated with
      the activity of EII(Fru).

PMID- 11238975
TI  - Molecular characterization, enzyme properties and transcriptional regulation of
      phosphoenolpyruvate carboxykinase and pyruvate kinase in a ruminal bacterium,
      Selenomonas ruminantium.
AB  - To elucidate the regulatory mechanism for propionate production in Selenomonas
      ruminantium, the molecular properties and gene expression of phosphoenolpyruvate
      carboxykinase (Pck) and pyruvate kinase (Pyk) were investigated. The Pck was
      deduced to consist of 538 aa with a molecular mass of 59.6 kDa, and appeared to
      exist as a monomer. The Pyk was revealed to consist of four identical subunits
      consisting of 469 aa with a molecular mass of 51.3 kDa. Both Mg(2+) and Mn(2+)
      were required for the maximal activity of Pck, and Pck utilized ADP, not GDP or
      IDP, as a substrate. Either Mg(2+) or Mn(2+) was required for Pyk activity, and
      the enzyme was activated by phosphoenolpyruvate (PEP) and fructose 1,6
      bisphosphate (FBP). Pyk activity was severely inhibited by P(i), but restored by
      the addition of FBP. The K:(m) value of Pck for PEP (0.55 mM) was nearly equal to
      the K:(m) value of Pyk for PEP, suggesting that the partition of the flow from
      PEP in the fermentation pathways is determined by the activity ratio of Pck to
      Pyk. Both pck and pyk genes were monocistronic, although two transcriptional
      start sites were found in pyk. The level of pyk mRNA was not different whether
      glucose or lactate was the energy substrate. However, the pck mRNA level was 12
      fold higher when grown on lactate than on glucose. The level of pck mRNA was
      inversely related to the sufficiency of energy, suggesting that Pck synthesis is
      regulated at the transcriptional level when energy supply is altered. It was
      conceivable that the transcription of pck in S. ruminantium is triggered by PEP
      and suppressed by ATP.

PMID- 11238976
TI  - A Corynebacterium glutamicum mutant with a defined deletion within the rplK gene
      is impaired in (p)ppGpp accumulation upon amino acid starvation.
AB  - The rplK gene of Corynebacterium glutamicum ATCC13032 comprises 438 nucleotides
      and encodes a protein of 145 amino acids with a molecular mass of 15.3 kDa. The
      amino acid sequence revealed extensive similarities to the large ribosomal
      subunit protein L11 from several Gram-positive and Gram-negative bacteria. The C.
      glutamicum rplK gene is located downstream of secE, representing part of the
      protein export apparatus, and of nusG, encoding a transcription antiterminator
      protein. The rplK gene is followed by an ORF homologous to rplA encoding the 50S
      ribosomal protein L1. Northern analysis revealed that transcription of the rplK
      rplA cluster resulted in two different transcripts of 1.5 and 0.6 kb. The 1.5 kb
      transcript corresponds to the entire rplK-rplA cluster and the short transcript
      originates from the rplK gene. A C. glutamicum rplK mutant strain carrying a 12
      bp in-frame deletion within rplK, which resulted in the loss of the tetrapeptide
      Pro-Ala-Leu-Gly in the L11 protein, was constructed. The mutant failed to
      accumulate (p)ppGpp in response to amino acid starvation and exhibited an
      increased tolerance to the antibiotic thiostrepton. Evidently, the C. glutamicum
      rplK gene is required for (p)ppGpp accumulation upon nutritional starvation.

PMID- 11238977
TI  - Transcription of arcA and rpoS during growth of Salmonella typhimurium under
      aerobic and microaerobic conditions.
AB  - Physiology of the exponential and stationary phase of growth, under both aerobic
      and microaerobic conditions, of Salmonella typhimurium and its isogenic mutants
      nuoG::Km, cydA::TnphoA, DeltaarcA and DeltarpoS was studied using luxAB
      transcriptional fusions with the rpoS and arcA genes. In the wild-type strain,
      rpoS transcription was greater under aerobic than under microaerobic conditions,
      whereas transcription of arcA was suppressed by aerobiosis. Under aerobic
      conditions, no interaction between NuoG, CydA, ArcA and RpoS was detected. Under
      microaerobic conditions, rpoS was suppressed in the nuoG mutant as compared with
      the wild-type strain, but it was overexpressed in the cydA and arcA mutants. A
      deletion in the rpoS gene, on the other hand, resulted in non-restricted,
      increased arcA expression in stationary-phase cultures under microaerobic
      conditions. Based on the rpoS transcription in the nuoG mutant the authors
      propose that the decrease in the NADH:NAD ratio that occurs when carbon sources
      become limiting serves as a signal for increased rpoS transcription, while active
      respiration catalysed by CydA and controlled by ArcA downregulates rpoS
      transcription. When, finally, the RpoS-controlled stationary phase of growth is
      reached, arcA is suppressed in an RpoS-dependent fashion. Transition into
      stationary phase under microaerobic conditions is thus controlled by coordinated
      action of the RpoS and ArcA regulators, depending on subtle changes in the
      environment.

PMID- 11238978
TI  - Escherichia coli acid resistance: cAMP receptor protein and a 20 bp cis-acting
      sequence control pH and stationary phase expression of the gadA and gadBC
      glutamate decarboxylase genes.
AB  - Acid resistance is an important feature of both pathogenic and non-pathogenic
      Escherichia coli. It enables survival in the acidic regions of mammalian
      gastrointestinal tracts and is largely responsible for the small number of
      bacteria required for infection/colonization. Three systems of acid resistance
      have been identified, the most efficient of which requires glutamic acid during
      pH 2 acid challenge. Three proteins associated with glutamate-dependent acid
      resistance have been identified. They are glutamate decarboxylase (encompassing
      two isozymes encoded by gadA and gadB) and a putative glutamate:gamma-amino
      butyric acid antiporter (encoded by gadC). The results confirm that the GadA and
      GadB proteins increase in response to stationary phase and low environmental pH.
      The levels of these proteins correspond to concomitant changes in gadA and gadBC
      mRNA levels. Fusions between lacZ and the gadA and gadBC operons indicate that
      this control occurs at the transcriptional level. Western blot, Northern blot and
      fusion analyses reveal that regulation of these genes is complex. Expression in
      rich media is restricted to stationary phase. However, in minimal media, acid pH
      alone can trigger induction in exponential or stationary phase cells. Despite
      this differential control, there is only one transcriptional start site for each
      gene. Expression in rich media is largely dependent on the alternate sigma factor
      sigma(S) and is repressed by the cAMP receptor protein (CRP). In contrast,
      sigma(S) has only a minor role in gad transcription in cells grown in minimal
      media. Deletions of the regulatory region upstream of gadA provided evidence that
      a 20 bp conserved region located 50 bp from the transcriptional start of both
      operons is required for expression.

PMID- 11238979
TI  - Regulation of acp1, encoding a non-aspartyl acid protease expressed during
      pathogenesis of Sclerotinia sclerotiorum.
AB  - When grown in the presence of sunflower cell walls, Sclerotinia sclerotiorum, an
      ubiquitous necrotrophic fungus, secretes several acid proteases including a non
      aspartyl protease. The gene acp1, encoding an acid protease, has been cloned and
      sequenced. The intronless ORF encodes a preproprotein of 252 aa and a mature
      protein of 200 residues. In vitro expression of acp1 is subject to several
      transcriptional regulatory mechanisms. Expression induced by plant cell-wall
      proteins is controlled by both carbon and nitrogen catabolite repression. Glucose
      on its own represses acp1 expression while ammonium repression requires the
      simultaneous presence of a carbon source. Ambient pH higher than pH 5 overrides
      induction resulting in full repression of acp1. These transcriptional regulatory
      mechanisms and the presence of several motifs in the promoter of acp1 that may
      encode binding sites for the regulators CREA, AREA and PacC suggest the
      involvement of these regulators in the control of acp1 expression. acp1 is
      expressed in planta during sunflower cotyledon infection. Expression is low at
      the beginning of infection but increases suddenly at the stage of necrosis
      spreading. Comparison of in vitro and in planta acp1 expression suggests that
      glucose and nitrogen starvation together with acidification can be considered as
      key factors controlling Scl. sclerotiorum gene expression during pathogenesis.

PMID- 11238980
TI  - Salmonella typhimurium thyA mutants fail to grow intracellularly in vitro and are
      attenuated in mice.
AB  - Salmonella typhimurium ATCC14028 readily multiplies in professional phagocytes in
      vitro and is highly virulent in mice. Mutants lacking thymidylate synthase
      activity (thyA) were isolated and shown to be strictly dependent on thymidine
      monophosphate precursors in the growth medium. The thyA mutants were found to be
      virtually incapable of intracellular growth and survival in vitro, both in
      macrophage-like cell line P338D(1) and in the human epithelial cell line Hep-2,
      and their virulence was impaired in BALB/c mice. Intraperitoneal immunization of
      mice with two doses of live S. typhimurium thyA provided protection against a
      challenge with 10(3) times the 50% lethal dose of the virulent parent strain.

PMID- 11238981
TI  - Campylobacter upsaliensis exerts a cytolethal distending toxin effect on HeLa
      cells and T lymphocytes.
AB  - Campylobacter upsaliensis is an emerging human enteropathogen. However, little is
      known about the pathogenesis of C. upsaliensis infection. In this study the
      authors demonstrate that C. upsaliensis whole-cell preparations and extracts
      produce a cytolethal distending toxin (CDT)-like effect on HeLa cells
      characterized by progressive distension and nuclear fragmentation culminating in
      cell death over 5 d. To further delineate the nature of this toxic effect in
      relation to CDT from other pathogens, the effect of C. upsaliensis on cellular
      events in epithelial cells and immunocytes was investigated. C. upsaliensis
      lysate-treated HeLa cells subjected to FACScan analysis using carboxyfluorescein
      diacetete succinimidyl ester (CFDA-SE) as a cell tracer demonstrated cell
      division arrest. Propidium iodide (PI) staining of HeLa cells revealed that cell
      cycle arrest occurred in G(2)/M. Human T lymphocytes exposed to C. upsaliensis
      lysates also showed cell cycle arrest in G(2)/M. Using a combination of Annexin
      V/PI staining and TUNEL assay, cytodistended HeLa cells were shown to undergo
      apoptotic cell death. These data provide the first insights into the virulence
      mechanisms of this novel enteropathogen.

PMID- 11238982
TI  - An inducible 1-butanol dehydrogenase, a quinohaemoprotein, is involved in the
      oxidation of butane by "Pseudomonas butanovora".
AB  - Butane-grown "Pseudomonas butanovora" expressed two soluble alcohol
      dehydrogenases (ADHs), an NAD(+)-dependent secondary ADH and an NAD(+)
      independent primary ADH. Two additional NAD(+)-dependent secondary ADHs could be
      detected when cells were grown on 2-butanol and lactate. The inducible NAD(+)
      independent 1-butanol dehydrogenase (BDH) of butane-grown cells was primarily
      responsible for 1-butanol oxidation in the butane metabolism pathway. BDH was
      purified to near homogeneity and identified as a quinohaemoprotein, containing,
      per mol enzyme, 1.0 mol pyrroloquinoline quinone (PQQ) and 0.25 mol haem c as
      prosthetic groups. BDH was synthesized as a monomer of approximately 66 kDa. It
      has a broad substrate range, including primary alcohols, secondary alcohols,
      aldehydes, C(4) diols and aromatic alcohols. It exhibited the lowest K:(m) (7+/-1
      microM) and highest k(cat)/K:(m) (72x10(4) M(-1) s(-1)) value towards 1-butanol.
      BDH exhibited ferricyanide-dependent ADH activity. Calcium ions (up to 10 mM)
      increased BDH activity substantially. Two BDH internal amino acid sequences
      showed 73 and 62% identity and 83 and 66% similarity, respectively, when compared
      with an amino acid sequence of ethanol dehydrogenase from Comamonas testosteroni.
      The presence of the inducible BDH and secondary ADH may indicate that the
      terminal and subterminal oxidation pathways are involved in butane degradation of
      butane-grown "P. butanovora".

PMID- 11238983
TI  - The electrophoretic softness of the surface of Staphylococcus epidermidis cells
      grown in a liquid medium and on a solid agar.
AB  - Many Staphylococcus epidermidis strains possess capsule or slime layers and
      consequently the staphylococcal cell surface should be regarded as a soft,
      polyelectrolyte layer allowing electrophoretic fluid flow through a layer of
      fixed charges. The presence of such a soft layer decreases the energy barrier due
      to electrostatic repulsion in the interaction of the organisms with negatively
      charged substrata [Morisaki, H., Nagai, S., Ohshima, H., Ikemoto, E. & Kogure, K.
      (1999), MICROBIOLOGY: 145, 2797-2802] and hence plays an important role in their
      adhesion. In this paper, the authors compare the electrophoretic softness and
      amount of fixed charge in the outer cell surface layers of 20 S. epidermidis
      strains, grown in a liquid medium or on a solid agar, as determined from the
      dependencies of their electrophoretic mobilities upon the ionic strength of a
      suspending fluid. Most of the staphylococcal cell surfaces were relatively soft,
      with a mean cell surface softness (1/lambda) for strains grown in liquid medium
      of 1.7+/-0.6 nm (standard deviation over all 20 strains) which is soft by
      comparison with a completely bald, peptidoglycan-rich streptococcal cell surface
      (1/lambda=0.7 nm). When the staphylococcal strains were grown on solid agar, the
      cell surface softness of 17 of the 20 strains increased, sometimes by a factor of
      two. On average for 20 strains, the cell surface softness increased significantly
      (P:<0.05, Student's t-test) to 2.8+/-1.8 nm. The amount of fixed charge in the
      outer cell surface layer was -28+/-9 mM for bacteria grown in liquid medium and 
      24+/-12 mM for bacteria grown on agar. A soft, highly negatively charged
      polyelectrolyte layer was inferred by microelectrophoresis for all the
      staphylococcal cell surfaces, regardless of whether staining had indicated the
      presence of a capsule or slime layer.

PMID- 11238987
TI  - Biosynthesis of polyketides in heterologous hosts.
AB  - Polyketide natural products show great promise as medicinal agents. Typically the
      products of microbial secondary biosynthesis, polyketides are synthesized by an
      evolutionarily related but architecturally diverse family of multifunctional
      enzymes called polyketide synthases. A principal limitation for fundamental
      biochemical studies of these modular megasynthases, as well as for their
      applications in biotechnology, is the challenge associated with manipulating the
      natural microorganism that produces a polyketide of interest. To ameliorate this
      limitation, over the past decade several genetically amenable microbes have been
      developed as heterologous hosts for polyketide biosynthesis. Here we review the
      state of the art as well as the difficulties associated with heterologous
      polyketide production. In particular, we focus on two model hosts, Streptomyces
      coelicolor and Escherichia coli. Future directions for this relatively new but
      growing technological opportunity are also discussed.

PMID- 11238988
TI  - Escherichia coli and Salmonella 2000: the view from here.
AB  - Five years after the publication of the second edition of the reference book
      Escherichia coli and Salmonella: Cellular and Molecular Biology, and on the eve
      of launching a successor venture, the editors and colleagues examine where we
      stand in our quest for an understanding of these organisms. The main areas
      selected for this brief inquiry are genomics, evolution, molecular
      multifunctionality, functional backups, regulation of gene expression, cell
      biology, sensing of the environment, and ecology.

PMID- 11238985
TI  - Genome of the extremely radiation-resistant bacterium Deinococcus radiodurans
      viewed from the perspective of comparative genomics.
AB  - The bacterium Deinococcus radiodurans shows remarkable resistance to a range of
      damage caused by ionizing radiation, desiccation, UV radiation, oxidizing agents,
      and electrophilic mutagens. D. radiodurans is best known for its extreme
      resistance to ionizing radiation; not only can it grow continuously in the
      presence of chronic radiation (6 kilorads/h), but also it can survive acute
      exposures to gamma radiation exceeding 1,500 kilorads without dying or undergoing
      induced mutation. These characteristics were the impetus for sequencing the
      genome of D. radiodurans and the ongoing development of its use for
      bioremediation of radioactive wastes. Although it is known that these multiple
      resistance phenotypes stem from efficient DNA repair processes, the mechanisms
      underlying these extraordinary repair capabilities remain poorly understood. In
      this work we present an extensive comparative sequence analysis of the
      Deinococcus genome. Deinococcus is the first representative with a completely
      sequenced genome from a distinct bacterial lineage of extremophiles, the Thermus
      Deinococcus group. Phylogenetic tree analysis, combined with the identification
      of several synapomorphies between Thermus and Deinococcus, supports the
      hypothesis that it is an ancient group with no clear affinities to any of the
      other known bacterial lineages. Distinctive features of the Deinococcus genome as
      well as features shared with other free-living bacteria were revealed by
      comparison of its proteome to the collection of clusters of orthologous groups of
      proteins. Analysis of paralogs in Deinococcus has revealed several unique protein
      families. In addition, specific expansions of several other families including
      phosphatases, proteases, acyltransferases, and Nudix family pyrophosphohydrolases
      were detected. Genes that potentially affect DNA repair and recombination and
      stress responses were investigated in detail. Some proteins appear to have been
      horizontally transferred from eukaryotes and are not present in other bacteria.
      For example, three proteins homologous to plant desiccation resistance proteins
      were identified, and these are particularly interesting because of the
      correlation between desiccation and radiation resistance. Compared to other
      bacteria, the D. radiodurans genome is enriched in repetitive sequences, namely,
      IS-like transposons and small intergenic repeats. In combination, these
      observations suggest that several different biological mechanisms contribute to
      the multiple DNA repair-dependent phenotypes of this organism.

PMID- 11238984
TI  - Hyperthermophilic enzymes: sources, uses, and molecular mechanisms for
      thermostability.
AB  - Enzymes synthesized by hyperthermophiles (bacteria and archaea with optimal
      growth temperatures of > 80 degrees C), also called hyperthermophilic enzymes,
      are typically thermostable (i.e., resistant to irreversible inactivation at high
      temperatures) and are optimally active at high temperatures. These enzymes share
      the same catalytic mechanisms with their mesophilic counterparts. When cloned and
      expressed in mesophilic hosts, hyperthermophilic enzymes usually retain their
      thermal properties, indicating that these properties are genetically encoded.
      Sequence alignments, amino acid content comparisons, crystal structure
      comparisons, and mutagenesis experiments indicate that hyperthermophilic enzymes
      are, indeed, very similar to their mesophilic homologues. No single mechanism is
      responsible for the remarkable stability of hyperthermophilic enzymes. Increased
      thermostability must be found, instead, in a small number of highly specific
      alterations that often do not obey any obvious traffic rules. After briefly
      discussing the diversity of hyperthermophilic organisms, this review concentrates
      on the remarkable thermostability of their enzymes. The biochemical and molecular
      properties of hyperthermophilic enzymes are described. Mechanisms responsible for
      protein inactivation are reviewed. The molecular mechanisms involved in protein
      thermostabilization are discussed, including ion pairs, hydrogen bonds,
      hydrophobic interactions, disulfide bridges, packing, decrease of the entropy of
      unfolding, and intersubunit interactions. Finally, current uses and potential
      applications of thermophilic and hyperthermophilic enzymes as research reagents
      and as catalysts for industrial processes are described.

PMID- 11238990
TI  - Transition between stochastic evolution and deterministic evolution in the
      presence of selection: general theory and application to virology.
AB  - We present here a self-contained analytic review of the role of stochastic
      factors acting on a virus population. We develop a simple one-locus, two-allele
      model of a haploid population of constant size including the factors of random
      drift, purifying selection, and random mutation. We consider different
      virological experiments: accumulation and reversion of deleterious mutations,
      competition between mutant and wild-type viruses, gene fixation, mutation
      frequencies at the steady state, divergence of two populations split from one
      population, and genetic turnover within a single population. In the first part of
      the review, we present all principal results in qualitative terms and illustrate
      them with examples obtained by computer simulation. In the second part, we derive
      the results formally from a diffusion equation of the Wright-Fisher type and
      boundary conditions, all derived from the first principles for the virus
      population model. We show that the leading factors and observable behavior of
      evolution differ significantly in three broad intervals of population size, N.
      The "neutral limit" is reached when N is smaller than the inverse selection
      coefficient. When N is larger than the inverse mutation rate per base, selection
      dominates and evolution is "almost" deterministic. If the selection coefficient
      is much larger than the mutation rate, there exists a broad interval of
      population sizes, in which weakly diverse populations are almost neutral while
      highly diverse populations are controlled by selection pressure. We discuss in
      detail the application of our results to human immunodeficiency virus population
      in vivo, sampling effects, and limitations of the model.

PMID- 11238986
TI  - P(II) signal transduction proteins, pivotal players in microbial nitrogen
      control.
AB  - The P(II) family of signal transduction proteins are among the most widely
      distributed signal proteins in the bacterial world. First identified in 1969 as a
      component of the glutamine synthetase regulatory apparatus, P(II) proteins have
      since been recognized as playing a pivotal role in control of prokaryotic
      nitrogen metabolism. More recently, members of the family have been found in
      higher plants, where they also potentially play a role in nitrogen control. The
      P(II) proteins can function in the regulation of both gene transcription, by
      modulating the activity of regulatory proteins, and the catalytic activity of
      enzymes involved in nitrogen metabolism. There is also emerging evidence that
      they may regulate the activity of proteins required for transport of nitrogen
      compounds into the cell. In this review we discuss the history of the P(II)
      proteins, their structures and biochemistry, and their distribution and functions
      in prokaryotes. We survey data emerging from bacterial genome sequences and
      consider other likely or potential targets for control by P(II) proteins.

PMID- 11238992
TI  - Gene2EST: a BLAST2 server for searching expressed sequence tag (EST) databases
      with eukaryotic gene-sized queries.
AB  - Expressed sequence tags (ESTs) are randomly sequenced cDNA clones. Currently,
      nearly 3 million human and 2 million mouse ESTs provide valuable resources that
      enable researchers to investigate the products of gene expression. The EST
      databases have proven to be useful tools for detecting homologous genes, for exon
      mapping, revealing differential splicing, etc. With the increasing availability
      of large amounts of poorly characterised eukaryotic (notably human) genomic
      sequence, ESTs have now become a vital tool for gene identification, sometimes
      yielding the only unambiguous evidence for the existence of a gene expression
      product. However, BLAST-based Web servers available to the general user have not
      kept pace with these developments and do not provide appropriate tools for
      querying EST databases with large highly spliced genes, often spanning 50 000-100
      000 bases or more. Here we describe Gene2EST (http://woody.embl
      heidelberg.de/gene2est/), a server that brings together a set of tools enabling
      efficient retrieval of ESTs matching large DNA queries and their subsequent
      analysis. RepeatMasker is used to mask dispersed repetitive sequences (such as
      Alu elements) in the query, BLAST2 for searching EST databases and Artemis for
      graphical display of the findings. Gene2EST combines these components into a Web
      resource targeted at the researcher who wishes to study one or a few genes to a
      high level of detail.

PMID- 11238991
TI  - A link between DNA methylation and epigenetic silencing in transgenic Volvox
      carteri.
AB  - Epigenetic silencing of foreign genes introduced into plants poses an unsolved
      problem for transgenic technology. Here we have used the simple multicellular
      green alga VOLVOX: carteri as a model to analyse the relation of DNA methylation
      to transgenic silencing. VOLVOX: DNA contains on average 1.1% 5-methylcytosine
      and 0.3% N6-methyladenine, as revealed by electrospray mass spectrometry and
      phosphoimaging of chromatographically separated (32)P-labelled nucleotides. In
      two nuclear transformants of V.carteri, produced in 1993 by biolistic bombardment
      with a foreign arylsulphatase gene (C-ars), the transgene is still expressed in
      one (Hill 181), but not in the other (Hill 183), after an estimated 500-1000
      generations. Each transformant clone contains multiple intact copies of C-ars,
      most of them integrated into the genome as tandem repeats. When the bisulphite
      genomic sequencing protocol was applied to examine two select regions of
      transgenic C-ars, we found that the inactivated copies (Hill 183) exhibited a
      high-level methylation (40%) of CpG dinucleotides, whereas the active copies
      (Hill 181) displayed low-level (7%) CpG methylation. These are average values
      from 40 PCR clones sequenced from each DNA strand in the two portions of C-ars.
      The observed correlation of CpG methylation and transgene inactivation in a green
      alga will be discussed in the light of transcriptional silencing.

PMID- 11238993
TI  - Methylation is not the main force repressing the retrotransposon MAGGY in
      Magnaporthe grisea.
AB  - We have introduced the LTR-retrotransposon MAGGY into a naive genome of
      Magnaporthe grisea and estimated the copy number of MAGGY in a cell by serial
      isolation of fungal protoplasts at certain time intervals. The number of MAGGY
      elements rapidly increased for a short period following introduction. However, it
      did not increase geometrically and reached equilibrium at 20-30 copies per
      genome, indicating that MAGGY was repressed or silenced during proliferation. De
      novo methylation of MAGGY occurred immediately following invasion into the genome
      but the degree of methylation was constant and did not correlate with the
      repression of MAGGY. 5-Azacytidine treatment demethylated and transcriptionally
      activated the MAGGY element in regenerants but did not affect transpositional
      frequency, suggesting that post-transcriptional suppression, not methylation, is
      the main force that represses MAGGY proliferation in M.grisea. Support for this
      conclusion was also obtained by examining the methylation status of MAGGY
      sequences in field isolates of M.grisea with active or inactive MAGGY elements.
      Methylation of the MAGGY sequences was detected in some isolates but not in
      others. However, the methylation status did not correlate with the copy numbers
      and activity of the elements.

PMID- 11238989
TI  - Molecular pathways in virus-induced cytokine production.
AB  - Virus infections induce a proinflammatory response including expression of
      cytokines and chemokines. The subsequent leukocyte recruitment and antiviral
      effector functions contribute to the first line of defense against viruses. The
      molecular virus-cell interactions initiating these events have been studied
      intensively, and it appears that viral surface glycoproteins, double-stranded
      RNA, and intracellular viral proteins all have the capacity to activate signal
      transduction pathways leading to the expression of cytokines and chemokines. The
      signaling pathways activated by viral infections include the major
      proinflammatory pathways, with the transcription factor NF-kappaB having received
      special attention. These transcription factors in turn promote the expression of
      specific inducible host proteins and participate in the expression of some viral
      genes. Here we review the current knowledge of virus-induced signal transduction
      by seven human pathogenic viruses and the most widely used experimental models
      for viral infections. The molecular mechanisms of virus-induced expression of
      cytokines and chemokines is also analyzed.

PMID- 11238994
TI  - Mechanism of stimulation of the DNA glycosylase activity of hOGG1 by the major
      human AP endonuclease: bypass of the AP lyase activity step.
AB  - The generation of reactive oxygen species in the cell provokes, among other
      lesions, the formation of 8-oxo-7,8-dihydroguanine (8-oxoG) in DNA. Due to
      mispairing with adenine during replication, 8-oxoG is highly mutagenic. To
      minimise the mutagenic potential of this oxidised purine, human cells have a
      specific 8-oxoG DNA glycosylase/AP lyase (hOGG1) that initiates the base excision
      repair (BER) of 8-oxoG. We show here that in vitro this first enzyme of the BER
      pathway is relatively inefficient because of a high affinity for the product of
      the reaction it catalyses (half-life of the complex is >2 h), leading to a lack
      of hOGG1 turnover. However, the glycosylase activity of hOGG1 is stimulated by
      the major human AP endonuclease, HAP1 (APE1), the enzyme that performs the
      subsequent step in BER, as well as by a catalytically inactive mutant (HAP1
      D210N). In the presence of HAP1, the AP sites generated by the hOGG1 DNA
      glycosylase can be occupied by the endonuclease, avoiding the re-association of
      hOGG1. Moreover, the glycosylase has a higher affinity for a non-cleaved AP site
      than for the cleaved DNA product generated by HAP1. This would shift the
      equilibrium towards the free glycosylase, making it available to initiate new
      catalytic cycles. In contrast, HAP1 does not affect the AP lyase activity of
      hOGG1. This stimulation of only the hOGG1 glycosylase reaction accentuates the
      uncoupling of its glycosylase and AP lyase activities. These data indicate that,
      in the presence of HAP1, the BER of 8-oxoG residues can be highly efficient by
      bypassing the AP lyase activity of hOGG1 and thus excluding a potentially rate
      limiting step.

PMID- 11238995
TI  - Fully modified 2' MOE oligonucleotides redirect polyadenylation.
AB  - Many genes have been described and characterized that have alternative
      polyadenylation signals at the 3'-end of their pre-mRNAs. Many of these same
      messages also contain destabilization motifs responsible for rapid degradation of
      the mRNA. Polyadenylation site selection can thus determine the stability of an
      mRNA. Fully modified 2'-O:-methoxy ethyl/phosphorothioate oligonucleotides that
      hybridize to the 3'-most polyadenylation site or signal of E-selectin were able
      to inhibit polyadenylation at this site and redirect it to one of two upstream
      cryptic sites. The shorter transcripts produced after antisense treatment have
      fewer destabilization sequences, increased mRNA stability and altered protein
      expression. This study demonstrates that antisense oligonucleotides can be
      successfully employed to redirect polyadenylation. This is the first
      demonstration of the use of oligonucleotides to increase, rather than decrease,
      abundance of a message.

PMID- 11238997
TI  - Molecular cloning of Ian4: a BCR/ABL-induced gene that encodes an outer membrane
      mitochondrial protein with GTP-binding activity.
AB  - Using the representation difference analysis technique, we have identified a
      novel gene, Ian4, which is preferentially expressed in hematopoietic precursor
      32D cells transfected with wild-type versus mutant forms of the Bcr/Abl oncogene.
      Ian4 expression was undetectable in 32D cells transfected with v-src, oncogenic
      Ha-ras or v-Abl. Murine Ian4 maps to chromosome 6, 25 cM from the centromere. The
      Ian4 mRNA contains two open reading frames (ORFs) separated by 5 nt. The first
      ORF has the potential to encode for a polypeptide of 67 amino acids without
      apparent homology to known proteins. The second ORF encodes a protein of 301
      amino acids with a GTP/ATP-binding site in the N-terminus and a hydrophobic
      domain in the extreme C-terminus. The IAN-4 protein resides in the mitochondrial
      outer membrane and the last 20 amino acids are necessary for this localization.
      The IAN-4 protein has GTP-binding activity and shares sequence homology with a
      novel family of putative GTP-binding proteins: the immuno-associated nucleotide
      (IAN) family.

PMID- 11238996
TI  - Human securin, hPTTG, is associated with Ku heterodimer, the regulatory subunit
      of the DNA-dependent protein kinase.
AB  - We have previously isolated the hpttg proto-oncogene, which is expressed in
      normal tissues containing proliferating cells and in several kinds of tumors. In
      fact, expression of hPTTG correlates with cell proliferation in a cell cycle
      dependent manner. Recently it was reported that PTTG is a vertebrate analog of
      the yeast securins Pds1 and Cut2, which are involved in sister chromatid
      separation. Here we show that hPTTG binds to Ku, the regulatory subunit of the
      DNA-dependent protein kinase (DNA-PK). hPTTG and Ku associate both in vitro and
      in vivo and the DNA-PK catalytic subunit phosphorylates hPTTG in vitro.
      Furthermore, DNA double-strand breaks prevent hPTTG-Ku association and disrupt
      the hPTTG-Ku complexes, indicating that genome damaging events, which result in
      the induction of pathways that activate DNA repair mechanisms and halt cell cycle
      progression, might inhibit hPTTG-Ku interaction in vivo. We propose that hPTTG
      might connect DNA damage-response pathways with sister chromatid separation,
      delaying the onset of mitosis while DNA repair occurs.

PMID- 11238998
TI  - DNA-binding and strand-annealing activities of human Mre11: implications for its
      roles in DNA double-strand break repair pathways.
AB  - DNA double-strand breaks (DSBs) in eukaryotic cells can be repaired by non
      homologous end-joining or homologous recombination. The complex containing the
      Mre11, Rad50 and Nbs1 proteins has been implicated in both DSB repair pathways,
      even though they are mechanistically different. To get a better understanding of
      the properties of the human Mre11 (hMre11) protein, we investigated some of its
      biochemical activities. We found that hMre11 binds both double- and single
      stranded (ss)DNA, with a preference for ssDNA. hMre11 does not require DNA ends
      for efficient binding. Interestingly, hMre11 mediates the annealing of
      complementary ssDNA molecules. In contrast to the annealing activity of the
      homologous recombination protein hRad52, the activity of hMre11 is abrogated by
      the ssDNA binding protein hRPA. We discuss the possible implications of the
      results for the role(s) of hMre11 in both DSB repair pathways.

PMID- 11238999
TI  - The dhp1(+) gene, encoding a putative nuclear 5'-->3' exoribonuclease, is
      required for proper chromosome segregation in fission yeast.
AB  - The Schizosaccharomyces pombe dhp1(+) gene is an ortholog of the Saccharomyces
      cerevisiae RAT1 gene, which encodes a nuclear 5'-->3' exoribonuclease, and is
      essential for cell viability. To clarify the cellular functions of the nuclear 5'
      ->3' exoribonuclease, we isolated and characterized a temperature-sensitive
      mutant of dhp1 (dhp1-1 mutant). The dhp1-1 mutant showed nuclear accumulation of
      poly(A)(+) RNA at the restrictive temperature, as was already reported for the
      rat1 mutant. Interestingly, the dhp1-1 mutant exhibited aberrant chromosome
      segregation at the restrictive temperature. The dhp1-1 cells frequently contained
      condensed chromosomes, most of whose sister chromatids failed to separate during
      mitosis despite normal mitotic spindle elongation. Finally, chromosomes were
      displaced or unequally segregated. As similar mitotic defects were also observed
      in Dhp1p-depleted cells, we concluded that dhp1(+) is required for proper
      chromosome segregation as well as for poly(A)(+) RNA metabolism in fission yeast.
      Furthermore, we isolated a multicopy suppressor of the dhp1-1 mutant, referred to
      as din1(+). We found that the gene product of dhp1-1 was unstable at high
      temperatures, but that reduced levels of Dhp1-1p could be suppressed by
      overexpressing Din1p at the restrictive temperature. Thus, Din1p may physically
      interact with Dhp1p and stabilize Dhp1p and/or restore its activity.

PMID- 11239000
TI  - Branched co-polymers of histidine and lysine are efficient carriers of plasmids.
AB  - We previously determined that a linear co-polymer of histidine and lysine (HK) in
      combination with liposomes enhanced the transfection efficiency of cationic
      liposomes. In the current study, we designed a series of HK polymers with
      increased branching and/or histidine/lysine ratio to determine if either variable
      affects transfection efficiency. In the presence of liposomes, the branched
      polymer with the highest number of histidines, HHK4b, was the most effective at
      enhancing gene expression. Furthermore, when serum was added to the medium during
      transfection, the combination of HHK4b and liposomes as a gene-delivery vehicle
      increased luciferase expression 400-fold compared to liposomes alone. In contrast
      to linear HK polymers, the higher branched HHK polymers were effective carriers
      of plasmids in the absence of liposomes. Without liposomes, the HHK4b carrier
      enhanced luciferase expression 15-fold in comparison with the lesser branched
      HHK2b carrier and increased expression by 5-logs in comparison with the HHK or HK
      carrier. The interplay of several parameters including increased condensation of
      DNA, buffering of acidic endosomes and differential binding affinities of polymer
      with DNA have a role in the enhancement of transfection by the HK polymers. In
      addition to suggesting that branched HK polymers are promising gene-delivery
      vehicles, this study provides a framework for the development of more efficient
      peptide-bond-based polymers of histidine and lysine.

PMID- 11239001
TI  - Chromatin-bound PCNA complex formation triggered by DNA damage occurs independent
      of the ATM gene product in human cells.
AB  - Proliferating cell nuclear antigen (PCNA), a processivity factor for DNA
      polymerases delta and epsilon, is involved in DNA replication as well as in
      diverse DNA repair pathways. In quiescent cells, UV light-induced bulky DNA
      damage triggers the transition of PCNA from a soluble to an insoluble chromatin
      bound form, which is intimately associated with the repair synthesis by
      polymerases delta and epsilon. In this study, we investigated the efficiency of
      PCNA complex formation in response to ionizing radiation-induced DNA strand
      breaks in normal and radiation-sensitive Ataxia telangiectasia (AT) cells by
      immunofluorescence and western blot techniques. Exposure of normal cells to gamma
      rays rapidly triggered the formation of PCNA foci in a dose-dependent manner in
      the nuclei and the PCNA foci (40-45%) co-localized with sites of repair synthesis
      detected by bromodeoxyuridine labeling. The chromatin-bound PCNA gradually
      declined with increasing post-irradiation times and almost reached the level of
      unirradiated cells by 6 h. The PCNA foci formed after gamma-irradiation was
      resistant to high salt extraction and the chromatin association of PCNA was lost
      after DNase I digestion. Interestingly, two radiosensitive primary fibroblast
      cell lines, derived from AT patients harboring homozygous mutations in the ATM
      gene, displayed an efficient PCNA redistribution after gamma-irradiation. We also
      analyzed the PCNA complex induced by a radiomimetic agent, Bleomycin (BLM), which
      produces predominantly single- and double-strand DNA breaks. The efficiency and
      the time course of PCNA complex induced by BLM were identical in both normal and
      AT cells. Our study demonstrates for the first time that the ATM gene product is
      not required for PCNA complex assembly in response to DNA strand breaks.
      Additionally, we observed an increased interaction of PCNA with the Ku70 and Ku80
      heterodimer after DNA damage, suggestive of a role for PCNA in the non-homologous
      end-joining repair pathway of DNA strand breaks.

PMID- 11239002
TI  - Comparative analysis of the gene-dense ACHE/TFR2 region on human chromosome 7q22
      with the orthologous region on mouse chromosome 5.
AB  - Chromosome 7q22 has been the focus of many cytogenetic and molecular studies
      aimed at delineating regions commonly deleted in myeloid leukemias and
      myelodysplastic syndromes. We have compared a gene-dense, GC-rich sub-region of
      7q22 with the orthologous region on mouse chromosome 5. A physical map of 640 kb
      of genomic DNA from mouse chromosome 5 was derived from a series of overlapping
      bacterial artificial chromosomes. A 296 kb segment from the physical map,
      spanning ACHE: to Tfr2, was compared with 267 kb of human sequence. We identified
      a conserved linkage of 12 genes including an open reading frame flanked by ACHE:
      and Asr2, a novel cation-chloride cotransporter interacting protein Cip1, Ephb4,
      Zan and Perq1. While some of these genes have been previously described, in each
      case we present new data derived from our comparative sequence analysis. Adjacent
      unfinished sequence data from the mouse contains an orthologous block of 10
      additional genes including three novel cDNA sequences that we subsequently mapped
      to human 7q22. Methods for displaying comparative genomic information, including
      unfinished sequence data, are becoming increasingly important. We supplement our
      printed comparative analysis with a new, Web-based program called Laj (local
      alignments with java). Laj provides interactive access to archived pairwise
      sequence alignments via the WWW. It displays synchronized views of a dot-plot, a
      percent identity plot, a nucleotide-level local alignment and a variety of
      relevant annotations. Our mouse-human comparison can be viewed at
      http://web.uvic.ca/~bioweb/laj.html. Laj is available at http://bio.cse.psu.edu/,
      along with online documentation and additional examples of annotated genomic
      regions.

PMID- 11239003
TI  - Mixed spermatogenic germ cell nuclear extracts exhibit high base excision repair
      activity.
AB  - Spermatogenic cells exhibit a lower spontaneous mutation frequency than somatic
      tissues in a lacI transgene and many base excision repair (BER) genes display the
      highest observed level of expression in the testis. In this study, uracil-DNA
      glycosylase-initiated BER activity was measured in nuclear extracts prepared from
      tissues obtained from each of three mouse strains. Extracts from mixed
      spermatogenic germ cells displayed the greatest activity followed by liver then
      brain for all three strains, and the activity for a given tissue was consistent
      among the three strains. Levels of various BER proteins were examined by western
      blot analyses and found to be consistent with activity levels. Nuclear extracts
      prepared from purified Sertoli cells, a somatic component of the seminiferous
      epithelium, exhibited significantly lower activity than mixed spermatogenic cell
      type nuclear extracts, thereby suggesting that the high BER activity observed in
      mixed germ cell nuclear extracts was not a characteristic of all testicular cell
      types. Nuclear extracts from thymocytes and small intestines were assayed to
      assess activity in a mitotically active cell type and tissue. Overall, the order
      of tissues/cells exhibiting the greatest to lowest activity was mixed germ cells
      > Sertoli cells > thymocytes > small intestine > liver > brain.

PMID- 11239004
TI  - The N- and C-terminal regions of RBP-J interact with the ankyrin repeats of
      Notch1 RAMIC to activate transcription.
AB  - The evolutionarily-conserved DNA-binding protein RBP-J directly interacts with
      the RAM domain and the ankyrin (ANK) repeats of the Notch intracellular region
      (RAMIC), and activates transcription of downstream target genes that regulate
      cell differentiation. In vitro binding assays demonstrate that the truncated N-
      and C-terminal regions of RBP-J bind to the ANK repeats but not to the RAM
      domain. Using an OT11 mouse cell line, in which the RBP-J locus is disrupted, we
      showed that RBP-J constructs mutated in the N- and C-terminal regions were
      defective in their transcriptional activation induced by either RAMIC or IC (the
      Notch intracellular region without the RAM domain) although they had normal
      levels of binding activity to DNA and the RAM domain. The studies using chimeric
      molecules between RBP-J and its homolog RBP-L showed that the N- and C-terminal
      regions of RBP-J conferred the IC- as well as RAMIC-induced transactivation
      potential on RBP-L, which binds to the same DNA sequence as RBP-J but fails to
      interact with RAMIC. Taken together, these results indicate that the interactions
      between the N- and C-terminal regions of RBP-J and the ANK repeats of RAMIC are
      important for transactivation of RBP-J by RAMIC.

PMID- 11239005
TI  - Inactivation of Saccharomyces cerevisiae OGG1 DNA repair gene leads to an
      increased frequency of mitochondrial mutants.
AB  - The OGG1 gene encodes a highly conserved DNA glycosylase that repairs oxidized
      guanines in DNA. We have investigated the in vivo function of the Ogg1 protein in
      yeast mitochondria. We demonstrate that inactivation of ogg1 leads to at least a
      2-fold increase in production of spontaneous mitochondrial mutants compared with
      wild-type. Using green fluorescent protein (GFP) we show that a GFP-Ogg1 fusion
      protein is transported to mitochondria. However, deletion of the first 11 amino
      acids from the N-terminus abolishes the transport of the GFP-Ogg1 fusion protein
      into the mitochondria. This analysis indicates that the N-terminus of Ogg1
      contains the mitochondrial localization signal. We provide evidence that both
      yeast and human Ogg1 proteins protect the mitochondrial genome from spontaneous,
      as well as induced, oxidative damage. Genetic analyses revealed that the combined
      inactivation of OGG1 and OGG2 [encoding an isoform of the Ogg1 protein, also
      known as endonuclease three-like glycosylase I (Ntg1)] leads to suppression of
      spontaneously arising mutations in the mitochondrial genome when compared with
      the ogg1 single mutant or the wild-type. Together, these studies provide in vivo
      evidence for the repair of oxidative lesions in the mitochondrial genome by human
      and yeast Ogg1 proteins. Our study also identifies Ogg2 as a suppressor of
      oxidative mutagenesis in mitochondria.

PMID- 11239007
TI  - OliI, a unique restriction endonuclease that recognizes the discontinuous
      sequence 5'-CACNN NGTG-3'.
AB  - A new type II restriction endonuclease designated OLI:I has been partially
      purified from the halophilic bacterium Oceanospirillum linum 4-5D. OLI:I
      recognizes the interrupted hexanucleotide palindrome 5'-CACNN NNGTG-3' and
      cleaves it in the center generating blunt-ended DNA fragments.

PMID- 11239006
TI  - Topological testing of the mechanism of homology search promoted by RecA protein.
AB  - To initiate homologous recombination, sequence similarity between two DNA
      molecules must be searched for and homology recognized. How the search for and
      recognition of homology occurs remains unproven. We have examined the influences
      of DNA topology and the polarity of RecA-single-stranded (ss)DNA filaments on the
      formation of synaptic complexes promoted by RecA. Using two complementary methods
      and various ssDNA and duplex DNA molecules as substrates, we demonstrate that
      topological constraints on a small circular RecA-ssDNA filament prevent it from
      interwinding with its duplex DNA target at the homologous region. We were unable
      to detect homologous pairing between a circular RecA-ssDNA filament and its
      relaxed or supercoiled circular duplex DNA targets. However, the formation of
      synaptic complexes between an invading linear RecA-ssDNA filament and covalently
      closed circular duplex DNAs is promoted by supercoiling of the duplex DNA. The
      results imply that a triplex structure formed by non-Watson-Crick hydrogen
      bonding is unlikely to be an intermediate in homology searching promoted by RecA.
      Rather, a model in which RecA-mediated homology searching requires unwinding of
      the duplex DNA coupled with local strand exchange is the likely mechanism.
      Furthermore, we show that polarity of the invading RecA-ssDNA does not affect its
      ability to pair and interwind with its circular target duplex DNA.

PMID- 11239008
TI  - RNA: a method to specifically inhibit PCR amplification of known members of a
      multigene family by degenerate primers.
AB  - The polymerase chain reaction (PCR) is a versatile method to amplify specific DNA
      with oligonucleotide primers. By designing degenerate PCR primers based on amino
      acid sequences that are highly conserved among all known gene family members, new
      members of a multigene family can be identified. The inherent weakness of this
      approach is that the degenerate primers will amplify previously identified, in
      addition to new, family members. To specifically address this problem, we
      synthesized a specific RNA for each known family member so that it hybridized to
      one strand of the template, adjacent to the 3'-end of the primer, allowing the
      degenerate primer to bind yet preventing extension by DNA polymerase. To test our
      strategy, we used known members of the soluble, nitric oxide-sensitive guanylyl
      cyclase family as our templates and degenerate primers that discriminate this
      family from other guanylyl cyclases. We demonstrate that amplification of known
      members of this family is effectively and specifically inhibited by the
      corresponding RNAs, alone or in combination. This robust method can be adapted to
      any application where multiple PCR products are amplified, as long as the
      sequence of the desired and the undesired PCR product(s) is sufficiently distinct
      between the primers.

PMID- 11239009
TI  - Defining the minimal length of sequence homology required for selective gene
      isolation by TAR cloning.
AB  - The transformation-associated recombination (TAR) cloning technique allows
      selective and accurate isolation of chromosomal regions and genes from complex
      genomes. The technique is based on in vivo recombination between genomic DNA and
      a linearized vector containing homologous sequences, or hooks, to the gene of
      interest. The recombination occurs during transformation of yeast spheroplasts
      that results in the generation of a yeast artificial chromosome (YAC) containing
      the gene of interest. To further enhance and refine the TAR cloning technology,
      we determined the minimal size of a specific hook required for gene isolation
      utilizing the Tg.AC mouse transgene as a targeted region. For this purpose a set
      of vectors containing a B1 repeat hook and a Tg.AC-specific hook of variable
      sizes (from 20 to 800 bp) was constructed and checked for efficiency of transgene
      isolation by a radial TAR cloning. When vectors with a specific hook that was
      >/=60 bp were utilized, approximately 2% of transformants contained circular YACs
      with the Tg.AC transgene sequences. Efficiency of cloning dramatically decreased
      when the TAR vector contained a hook of 40 bp or less. Thus, the minimal length
      of a unique sequence required for gene isolation by TAR is approximately 60 bp.
      No transgene-positive YAC clones were detected when an ARS element was
      incorporated into a vector, demonstrating that the absence of a yeast origin of
      replication in a vector is a prerequisite for efficient gene isolation by TAR
      cloning.

PMID- 11239010
TI  - Breaksite batch mapping, a rapid method for assay and identification of DNA
      breaksites in mammalian cells.
AB  - DNA breaks occur during many processes in mammalian cells, including
      recombination, repair, mutagenesis and apoptosis. Here we report a simple and
      rapid method for assaying DNA breaks and identifying DNA breaksites. Breaksites
      are first tagged and amplified by ligation-mediated PCR (LM-PCR), using nested
      PCR primers to increase the specificity and sensitivity of amplification.
      Breaksites are then mapped by batch sequencing LM-PCR products. This allows easy
      identification of multiple breaksites per reaction without tedious fractionation
      of PCR products by gel electrophoresis or cloning. Breaksite batch mapping
      requires little starting material and can be used to identify either single- or
      double-strand breaks.

PMID- 11239012
TI  - Potential role of retinoids in the therapy of renal disease.

PMID- 11239011
TI  - Fluorescent quenching-based quantitative detection of specific DNA/RNA using a
      BODIPY((R)) FL-labeled probe or primer.
AB  - We have developed a simple method for the quantitative detection of specific DNA
      or RNA molecules based on the finding that BODIPY((R)) FL fluorescence was
      quenched by its interaction with a uniquely positioned guanine. This approach
      makes use of an oligonucleotide probe or primer containing a BODIPY((R)) FL
      modified cytosine at its 5'-end. When such a probe was hybridized with a target
      DNA, its fluorescence was quenched by the guanine in the target, complementary to
      the modified cytosine, and the quench rate was proportional to the amount of
      target DNA. This widely applicable technique will be used directly with larger
      samples or in conjunction with the polymerase chain reaction to quantify small
      DNA samples.

PMID- 11239014
TI  - The evolving pattern of calciphylaxis: therapeutic considerations.

PMID- 11239013
TI  - A heart price to pay for anaemia.

PMID- 11239015
TI  - Renal determinants of the salt sensitivity of blood pressure.

PMID- 11239016
TI  - Cardiovascular disease determinants in chronic renal failure: clinical approach
      and treatment.
AB  - INTRODUCTION: Cardiovascular disease (CVD), as the leading cause of morbidity and
      mortality in patients on renal replacement therapy (RRT), has a central role in
      everyday nephrological practice. METHODS: Consensus was reached on key points
      relating to the clinical approach and treatment of the main cardiovascular risk
      factors in RRT patients (hypertension, anaemia, hyperparathyroidism,
      dyslipidaemia, new emerging risk factors). In addition, the role of convective
      treatments on cardiovascular outcomes was examined. RESULTS: Hypertension should
      be managed by aiming at blood pressure values of < or =140/90 mmHg (< or =160/90
      mmHg in the elderly), firstly by ensuring target dry body weight is achieved. No
      single class of drug has proved superior to others in RRT patients, provided that
      the blood pressure target is achieved, although ACE inhibitors have shown
      specific organ protection in high-risk patients (HOPE study) and are well
      tolerated. Anaemia should be managed by using erythropoietin and iron
      supplements, aiming at haemoglobin levels of 12 g/dl and keeping serum ferritin
      levels < 500 ng/ml. The management of hyperparathyroidism is currently
      unsatisfactory, as calcium supplements have the potential to increase
      cardiovascular calcification. While awaiting new calcium- and aluminium-free
      phosphate binders, it is essential to ensure dialysis adequacy. Clinical studies
      are in progress to assess the real impact of lipid-lowering drugs in RRT. In the
      meantime, serum LDL-cholesterol < 160 mg/dl and triglycerides < 500 mg/dl may be
      desirable targets. The impact of new emerging risk factors (inflammation and
      chronic infection, hyperhomocysteinaemia, metabolic waste-product accumulation)
      and their proper management are still under research. Convective dialysis
      treatments may confer some degree of protection from dialysis-related amyloidosis
      and mortality, but clinical data on this important issue are still controversial
      and no definitive conclusions can be drawn at present. CONCLUSION: CVD prevention
      and treatment is a great challenge for the nephrologist. Achieving evidence-based
      consensus can help in encouraging the implementation of best clinical practice in
      line with the progress of current knowledge.

PMID- 11239017
TI  - Controversy on optimal blood pressure on haemodialysis: normotensive blood
      pressure values are essential for survival.

PMID- 11239018
TI  - Controversy on optimal blood pressure on haemodialysis: lower is not always
      better.

PMID- 11239019
TI  - Glucocorticoid decreases circulating osteoprotegerin (OPG): possible mechanism
      for glucocorticoid induced osteoporosis.
AB  - BACKGROUND: Osteoporosis is a well known side-effect of long-term treatment with
      glucocorticoids. However, the precise mechanism of this disorder is unclear.
      Recently, osteoprotegerin (OPG) [osteoclastogenesis inhibitory factor (OCIF)] has
      been identified as a novel cytokine, which inhibits differentiation and
      activation of osteoclast. In the present study, in order to clarify the roles of
      OPG in the development of glucocorticoid-induced osteoporosis, we measured
      circulating OPG before and after glucocorticoid therapy. METHODS: The study
      subjects were 12 patients (five males, seven females, 53.4 +/- 4.8 [SE] years)
      with various renal diseases that required glucocorticoid therapy. All patients
      received glucocorticoids for the first time. Treatment was initiated at an
      average dose of 32.5 +/- 3.0 mg per day. Serum OPG was measured using enzyme
      linked immunosorbent assay (ELISA). Laboratory data, markers of bone metabolism
      and circulating OPG were compared before and after treatment for 4 weeks.
      RESULTS: Serum OPG prior to glucocorticoid therapy was positively and
      independently correlated with serum creatinine. Serum OPG decreased significantly
      (P: < 0.0001) from 1.03 +/- 0.14 to 0.77 +/- 0.12 ng/ml after short-term
      administration of glucocorticoids. Furthermore, serum osteocalcin as a marker of
      bone formation was also reduced markedly (P: = 0.001). On the other hand, there
      were no remarkable changes in serum calcium, total alkaline phosphatases,
      creatinine and intact parathyroid hormone in response to glucocorticoid
      administration. CONCLUSION: These findings indicate that short-term
      administration of glucocorticoids significantly suppresses serum OPG and
      osteocalcin. It might participate in the development of glucocorticoid-induced
      osteoporosis via an enhancement of bone resorption and suppression of bone
      formation.

PMID- 11239020
TI  - Apoptosis induced by hypertonicity in Madin Darley canine kidney cells:
      protective effect of betaine.
AB  - BACKGROUND: In mammals, the renal medulla is in a hypertonic environment related
      to the renal concentrating mechanism. Renal cells accumulate osmolytes such as
      betaine to protect cells from the perturbing effect of high concentration of
      electrolytes. Hypertonicity-induced cell death and the effect of betaine were
      investigated in Madin Darby canine kidney (MDCK) cells. METHODS: Cell viability
      was detected by 3-(4,5-dimethylthiazo-2-yl)-2,5-diphenyl tetrazolium bromide
      assay. DNA fragmentation was determined by FACS analysis, terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) staining
      and agarose gel electrophoresis. Activities of caspase-1, -3, -8, and -9 were
      measured. RESULT: When the cells were exposed to 700 mOsm medium for 24 h, 40% of
      the cells were detached. TUNEL staining showed that about 20% of detached cells
      were apoptotic, indicating that both necrosis and apoptosis contributed to the
      hypertonicity-induced cell death in MDCK cells. DNA laddering was demonstrated in
      hypertonic cells. Caspase-3, -8, and -9 activities of the adherent cells exposed
      to 700 mOsm for 24 h increased approximately 20-, 3-, and 4-fold the value of
      isotonic cells, respectively. However, there was no significant change in caspase
      1 activity. Addition of 1 mM betaine into the medium protected the cells against
      the hypertonicity-induced cytotoxicity and apoptosis. Betaine prevented the
      induction of caspase-3, -8, and -9 activities after hypertonic exposure to about
      50%. CONCLUSIONS: The present study demonstrates that (i) apoptosis is involved
      in the hypertonicity-induced cell death in MDCK cells; (ii) caspase-3, -8, and -9
      may contribute to the apoptosis; and (iii) betaine has protective effect on the
      hypertonicity-induced apoptosis.

PMID- 11239021
TI  - Erythropoietin modulates angiotensin II- or noradrenaline-induced Ca(2+)
      mobilization in cultured rat vascular smooth-muscle cells.
AB  - BACKGROUND: It has been reported that human recombinant erythropoietin (rHuEpo)
      modulates the sensitivity of the cardiovascular system to angiotensin II (Ang II)
      or noradrenaline (NA). In the present study, we explored the effect of rHuEpo on
      the responsiveness of Ang II- or NA-induced cytosolic free calcium ([Ca(2+)]i)
      mobilization in cultured rat vascular smooth-muscle cells (VSMC). METHODS:
      [Ca(2+)]i concentrations in VSMC were measured by using the calcium-sensitive
      fluorescent dye fura-2. RESULTS: The addition of rHuEpo (250 U/ml) alone induced
      elevation in [Ca(2+)]i, which remained significantly elevated above basal level
      for at least 60 min in the presence of extracellular Ca(2+). Pre-incubation with
      specific protein kinase C (PKC) inhibitor calphostin C (1 micromol/l)
      significantly reduced the peak and the sustained elevations of [Ca(2+)]i. Pre
      treatment with rHuEpo for 60 min increased both basal [Ca(2+)]i and the changes
      in [Ca(2+)]i by Ang II or NA in a dose-dependent manner in the presence of
      extracellular Ca(2+). The synergistic effects of rHuEpo with Ang II or NA were
      also retained when VSMC were bathed in the Ca(2+)-free medium after the pre
      incubation of rHuEpo. Conversely, they were diminished in the presence of
      extracellular Ca(2+) combined with intracellular Ca(2+) release inhibitor 8-(NN
      diethylamino)octyl-1,3,4,5-trimethoxybenzoate (TMB-8). The synergistic effects of
      rHuEpo were also diminished by PKC depletion or by PKC inhibitor. CONCLUSIONS:
      These observations suggest that rHuEpo has synergistic effects on Ang II- or NA
      induced [Ca(2+)]i mobilization, particularly on intracellular Ca(2+) release, in
      VSMC. This may be a potential mechanism contributing to hypertension associated
      with rHuEpo therapy.

PMID- 11239022
TI  - Cyclosporin A affects extracellular matrix synthesis and degradation by mouse
      MC3T3-E1 osteoblasts in vitro.
AB  - BACKGROUND: Immunosuppressant therapy is thought to be a major contributor to
      post-transplant bone disease. Histological data and serum parameters suggest that
      Cyclosporin A (CsA) treatment causes osteopenia as a result of an altered bone
      turnover, but the pathogenic mechanisms of this process remain unclear. We
      investigate if CsA affects cell turnover and extracellular matrix (ECM) synthesis
      and degradation in MC3T3-E1 osteoblasts, as a surrogate model for in vivo events.
      METHODS: Cells were exposed to increasing doses of CsA (0, 0.5, 1 and 5
      microg/ml). Proliferation was evaluated by bromodeoxyuridine (BrdU)
      incorporation, viability by Trypan Blue exclusion and apoptosis by ELISA. Type I
      collagen was measured by ELISA and reverse transcription-polymerase chain
      reaction (RT-PCR), matrix metalloproteinases (MMP) by zymography and RT-PCR, and
      tissue inhibitors of MMP (TIMP) by reverse zymography. RESULTS: CsA exposure for
      48 h decreased osteoblast number in a dose-dependent manner in the absence of
      apoptosis or cytotoxicity. CsA at a dose of 5 microg/ml for 72 h caused decreased
      collagen type I mRNA expression and protein accumulation. While MMP-2 remained
      unaffected, MMP-9 activity increased. TIMP-1 activity was unaffected, while a
      dose-dependent increase of TIMP-2 was observed. CONCLUSIONS: These data suggest
      that CsA alters ECM synthesis and degradation in MC3T3-E1 osteoblasts by
      decreasing type I collagen production and increasing MMP-9 activity. The
      combination of increased MMP-9 with unchanged TIMP-1 activity could reduce the
      osteoid matrix available for mineralization. In addition, decreased proliferation
      could further reduce the number of cells synthesizing new osteoid matrix and thus
      contribute to the process of bone loss.

PMID- 11239023
TI  - Failure of high doses of calcitriol and hypercalcaemia to induce apoptosis in
      hyperplastic parathyroid glands of azotaemic rats.
AB  - BACKGROUND: Whether calcitriol administration, which is used to treat secondary
      hyperparathyroidism in dialysis patients, induces regression of parathyroid-gland
      hyperplasia remains a subject of interest and debate. If regression of the
      parathyroid gland were to occur, the presumed mechanism would be apoptosis.
      However, information on whether high doses of calcitriol can induce apoptosis of
      parathyroid cells in hyperplastic parathyroid glands is lacking. Consequently,
      high doses of calcitriol were given to azotaemic rats and the parathyroid glands
      were evaluated for apoptosis. METHODS: Rats were either sham-operated (two
      groups) or underwent a two-stage 5/6 nephrectomy (three groups). For the first 4
      weeks, all rats were given a high (1.2%) phosphorus (P) diet to stimulate
      parathyroid gland growth and then were changed to a normal (0.6%) P diet for 2
      weeks. At week 7, three of the five groups were given high doses of calcitriol
      (500 pmol/100 g body weight) intraperitoneally every 24 h during 72 h before
      sacrifice. The five groups during week 7 were: (i) normal renal function
      (NRF)+0.6% P diet; (ii) NRF+0.6% P+calcitriol; (iii) renal failure (RF)+0.6% P;
      (iv) RF+1.2% P+calcitriol; and (v) RF+0.6% P+calcitriol. Parathyroid glands were
      removed at sacrifice and the TUNEL stain was performed to detect apoptosis.
      RESULTS: At sacrifice, the respective serum calcium values in calcitriol-treated
      groups (groups 2, 4, and 5) were 15.52+/-0.26, 13.41+/-0.39 and 15.12+/-0.32
      mg/dl. In group 3, PTH was 178+/-42 pg/ml, but in calcitriol-treated groups, PTH
      values were suppressed, 8+/-1 (group 2), 12+/-2 (group 4), and 7+/-1 pg/ml (group
      5). Despite, the severe hypercalcaemia and marked PTH suppression in calcitriol
      treated groups, the percentage of apoptotic cells in the parathyroid glands was
      very low (range 0.08+/-0.04 to 0.25+/-0.20%) and not different among the five
      groups. CONCLUSIONS: We found no evidence in hyperplastic parathyroid glands that
      apoptosis could be induced in azotaemic rats by the combination of high doses of
      calcitriol and severe hypercalcaemia despite the marked reduction in PTH levels
      that was observed.

PMID- 11239024
TI  - Increased intestinal intra-epithelial T lymphocytes in primary
      glomerulonephritis: a role of oral tolerance breakdown in the pathophysiology of
      human primary glomerulonephritides?
AB  - BACKGROUND: There is increasing evidence that some organ-specific and generalized
      autoimmune diseases in humans might be related to a breakdown of oral tolerance.
      We explored this hypothesis in human primary glomerulonephritides. We
      prospectively counted intraepithelial T lymphocytes in the duodenal mucosa (as a
      marker of rupture of oral tolerance), together with IgA1 and IgA2 mucosal plasma
      cells, in patients with primary glomerulonephritides. METHODS: We investigated
      eight adults with immune-complex glomerulopathy (membranous
      nephropathy+membranoproliferative glomerulonephritis), 16 adults with an
      idiopathic nephrotic syndrome, and 25 adults with IgA nephropathy. Patients with
      glomerulonephritides were compared to two control groups: group 1 consisted of
      nine healthy adults; group 2 comprised five adults with coeliac disease before
      dietary gluten withdrawal or during a clinical relapse related to gluten
      ingestion. (The latter disease is associated with increased numbers of
      intraepithelial T lymphocytes, and a breakdown of oral tolerance to gliadins is
      involved in the pathogenesis of coeliac disease). Duodenal fibroscopy was
      performed under neuroleptanalgesia. Four to six endoscopic biopsy specimens were
      taken from the second duodenum. Intraepithelial T lymphocytes were blindly
      counted on paraffin sections stained with haematein-eosin-saffron (HES), within
      the epithelium of a villus in a zone with at least 100 cells. Mucosal IgA1 and
      IgA2 plasma cells were blindly counted in a mucosal tissue unit by using specific
      mouse monoclonal antibodies directed against IgA1 and IgA2, with alkaline
      phosphatase anti-alkaline phosphatase (APAAP) revelation. As values were not
      normally distributed, we used non-parametric analysis of variance with the
      Kruskal-Wallis test, and compared median values by using the non-parametric Mann
      Whitney test. RESULTS: Intraepithelial T lymphocytes were significantly more
      abundant in patients with primary glomerulonephritides and coeliac disease than
      in healthy controls (P < 0.0001 in the Kruskal-Wallis test): healthy controls,
      median 11 (range 4.65-16); immune complex glomerulopathy, 27.45*** (15-93);
      idiopathic nephrotic syndrome, 16.5** (9-26.5); IgA nephropathy, 26.10*** (11.3
      47.5); coeliac disease, 55*** (20-80) (*P <0.05; **P <0.01; ***P < 0.005, Mann
      Whitney test). No difference was found in the number of duodenal IgA1 and IgA2
      plasma cells between controls and patients with primary glomerulonephritides.
      IgA1 and IgA2 plasma cells were increased in patients with coeliac disease.
      CONCLUSION: The significant increase in intestinal intraepithelial T lymphocytes
      in primary glomerulonephritides suggests a pathophysiological role of oral
      tolerance breakdown.

PMID- 11239025
TI  - Prevention and treatment of experimental crescentic glomerulonephritis by
      blocking tumour necrosis factor-alpha.
AB  - BACKGROUND: The mechanisms controlling progression of glomerulonephritis are
      poorly understood, but there is increasing evidence that tumour necrosis factor
      alpha (TNF-alpha) plays a central role in many aspects of glomerular inflammation
      and scarring. We investigated the role of TNF-alpha in an experimental model of
      crescentic glomerulonephritis in Wistar Kyoto (WKY) rats by continuously blocking
      endogenous TNF-alpha, using its soluble receptor sTNFr p55, both before and after
      establishment of nephritis. METHODS: Glomerulonephritis was induced by a single
      intravenous injection of 0.1 ml nephrotoxic serum. In the first experiment, rats
      were pre-treated with sTNFr p55 2 mg/kg intraperitoneally 1 hour before induction
      of nephritis and on a daily basis thereafter until day 4. In the second
      experiment, a similar protocol was followed, but treatment with sTNFr p55 was
      continued until day 10. In the third experiment, treatment with sTNFr p55 was
      delayed until 4 days after induction of nephritis and continued until day 10. The
      effects of treatment on renal function, renal histology, cellular infiltration,
      activation and proliferation, and IL-1beta expression were assessed by standard
      methods. RESULTS: In the first experiment, short-term treatment with sTNFr p55
      caused a marked reduction in albuminuria and fibrinoid necrosis. It also reduced
      glomerular cell infiltration, activation and proliferation. In the second
      experiment, prolonged treatment with sTNFr p55 caused a sustained reduction in
      albuminuria and all histological and cellular parameters of glomerular
      inflammation; in particular it completely prevented the development of crescents.
      In the third experiment, delayed therapy of established nephritis with sTNFr p55
      significantly reduced albuminuria and glomerular inflammation, including the
      prevalence of crescent formation. In both long-term experiments, there was less
      glomerular expression of IL-1beta and lower serum concentrations of IL-beta in
      sTNFr p55-treated rats. CONCLUSIONS: This study shows that neutralization of
      endogenous TNF-alpha is effective in preventing acute glomerular inflammation and
      crescent formation, and in treating established disease, in a rat model of
      crescentic nephritis. These results may have therapeutic implications for human
      glomerulonephritis.

PMID- 11239026
TI  - Adult height and proteinuria in type 2 diabetes.
AB  - BACKGROUND: Short stature has been shown to be associated with proteinuria in
      type 1 diabetes, but no data exist with respect to type 2 diabetes. The objective
      of the study was to investigate the relationship between final adult height and
      macroproteinuria in type 2 diabetic patients. METHODS: One hundred and forty-four
      consecutive type 2 diabetic patients (84 males, 60 females) with macroproteinuria
      were recruited into the study. For every patient, three diabetic controls matched
      for age, gender, and duration of diabetes were randomly selected. Height was
      measured in patients and controls to the nearest 0.5 cm. RESULTS: The mean height
      in men with macroproteinuria (n = 84) was 164.4 cm (SD 6.74) compared to 166.6 cm
      (SD 6.64) in controls (n = 252) (P < 0.01). The mean height in women with
      macroproteinuria (n = 60) was 150.6 cm (SD 5.20) compared to 152.5 cm (SD 5.78)
      in controls (n = 180) (P < 0.02). CONCLUSION: Short stature is associated with an
      increased risk of macroproteinuria in type 2 diabetic patients. We postulate that
      common genetic or environmental factors that affect final adult height might also
      predispose to the development of nephropathy.

PMID- 11239027
TI  - Prognostic implications of retinopathy and a high plasma von Willebrand factor
      concentration in type 2 diabetic subjects with microalbuminuria.
AB  - BACKGROUND: Microalbuminuria in subjects with type 2 diabetes may be
      heterogeneous with respect to clinical features, renal histology, and prognosis.
      There may be at least two types of microalbuminuria in diabetes, namely with and
      without generalized endothelial dysfunction. We investigated whether, among
      microalbuminuric subjects with type 2 diabetes, the presence of generalized
      endothelial dysfunction, as indicated by the presence of retinopathy or a high
      plasma von Willebrand factor (vWf) level, has prognostic implications. METHODS:
      In 173 type 2 diabetic subjects of a population-based cohort, we assessed the
      urinary albumin-to-creatinine ratio, the plasma vWf level, and the presence of
      retinopathy. The main outcome was cardiovascular mortality. RESULTS: The absolute
      difference in 7 years' cardiovascular mortality between microalbuminuric (albumin
      to-creatinine ratio 2.0-30.0 mg/mmol) and normoalbuminuric subjects was higher in
      the presence as compared to the absence of retinopathy (55.6 vs 11.1%). The age-
      and sex-adjusted relative risk (95% confidence interval) of cardiovascular
      mortality, as compared to normoalbuminuric subjects without retinopathy, was 1.1
      (0.1-9.2) for normoalbuminuric subjects with retinopathy, 1.8 (0.5-6.7) for
      microalbuminuric subjects without retinopathy, and 9.8 (3.1-30.9) for
      microalbuminuric subjects with retinopathy. The absolute difference in risk of 7
      years' cardiovascular mortality between microalbuminuric and normoalbuminuric
      subjects was higher in the presence as compared to the absence of a high (>1.89
      IU/ml) vWf level (49.8 vs 16.4%). The age- and sex-adjusted relative risk of
      cardiovascular mortality, as compared to normoalbuminuric subjects without a high
      vWf level, was 1.5 (0.4-5.5) for normoalbuminuric subjects with a high vWf level,
      2.6 (0.7-9.6) for microalbuminuric subjects without a high vWf level, and 12.0
      (2.9-49.5) for microalbuminuric subjects with a high vWf level. These differences
      in risk of cardiovascular mortality did not change materially after further
      adjustment for known duration of diabetes, hypertension, creatinine clearance,
      level of glycated haemoglobin and high-density lipoprotein cholesterol, and
      presence of cardiovascular disease. Analysis of all-cause instead of
      cardiovascular mortality showed a similar difference in risk of mortality between
      microalbuminuric subjects with or without retinopathy or a high vWf level.
      CONCLUSIONS: Among type 2 diabetic subjects with microalbuminuria, the presence
      of retinopathy or a high plasma vWf level affects the risk of cardiovascular
      death. Although larger studies are necessary, these findings support the concept
      that microalbuminuria in type 2 diabetes can occur in the absence or the presence
      of generalized endothelial dysfunction, and that the latter is a much more
      'malignant' condition than the former.

PMID- 11239028
TI  - Renal vascular changes in renal disease independent of hypertension.
AB  - INTRODUCTION: Cardiovascular disease is common in patients with renal disease,
      but little is known about the effect of renal disease and loss of renal function
      on vascular morphology. Intima proliferation of small renal arteries, which
      correlates with atherosclerosis in the aorta, is sometimes present in renal
      disease and has been shown to increase with age and hypertension. We studied the
      effect of chronic renal disease and renal function, independent of hypertension,
      on intima proliferation. METHODS: We retrospectively selected renal biopsies of
      subjects in whom a glomerular filtration rate (GFR) measurement with [(125)I]
      iothalamate had been performed. To separate the effects of renal disease and
      renal function, we selected biopsies from (A) normotensive controls undergoing
      nephrectomy because of renal carcinomas; (B) normotensive patients with renal
      disease and GFR > 90 ml/min; (C) normotensive patients with GFR 30-90 ml/min, and
      (D) hypertensive patients with a GFR < 90 ml/min. The area of the arteriolar
      lumen, intima, and media were measured. RESULTS: No significant changes from
      control subjects were observed in group B. Intima proliferation was observed when
      renal function declined (intima/total vessel surface ratio was 0.262 +/- 0.071 in
      group C, 0.192 +/- 0.032 in group A, and 0.205 +/- 0.035 in group B, P < 0.05).
      The intima proliferation was aggravated in patients with renal insufficiency and
      hypertension (0.333 +/- 0.121, P < 0.05). Media surface area was not different
      between groups. CONCLUSION: Renal disease with preserved GFR does not cause
      significant intima proliferation of small renal arteries. Loss of renal function
      is accompanied by intima proliferation, even in the absence of systemic
      hypertension.

PMID- 11239029
TI  - Mesna: a novel renoprotective antioxidant in ischaemic acute renal failure.
AB  - BACKGROUND: Reactive oxygen species (ROS) play a key role in renal ischaemia
      reperfusion injury. After establishing the in vitro anti-oxidative potential of
      mesna, a sulfhydryl-containing compound, its effect on kidney function and
      morphology in a rat model of ischaemic acute renal failure (ARF) was examined.
      METHODS: Mesna (180 mg/kg) was administered at different time points relative to
      ischaemia and/or reperfusion onset. Kidney function was assessed by glomerular
      filtration rate (GFR) and fractional sodium excretion (FE(Na)) before a 45-min
      period of unilateral renal artery clamping and following 90 min of reperfusion.
      Mesna was administered by bolus, 30 min before the induction of ischaemia, 5 min
      before ischaemia, 5 min before reperfusion, and 5 min after the onset of
      reperfusion. RESULTS: Mesna improved function of the ischaemic kidney at each
      administration. When mesna was administered 5 min before the onset of
      reperfusion, GFR reached 90-100% of its pre ischaemic value and FE(Na) was
      improved by 75%. The beneficial effect of mesna was also demonstrated by light
      and electron microscopy. Kidneys treated with mesna 5 min before reperfusion
      resembled ischaemic non-reperfused kidneys and showed subtle morphological and
      ultrastructural changes compared with ischaemic-reperfused kidneys. Mesna had no
      haemodynamic effect on renal blood flow and did not induce any osmotic diuresis.
      CONCLUSIONS: We suggest that mesna acts as an antioxidant. Its antioxidant
      potential together with optimal protection achieved when administered 5 min
      before reperfusion, supports the conclusion that mesna scavenges ROS generated at
      the onset of reperfusion, thus diminishing reperfusion injury and organ damage.

PMID- 11239030
TI  - Intraplatelet calcium levels in patients with acute renal failure before and
      after the administration of loop diuretics.
AB  - BACKGROUND: Intracellular calcium [Ca](i) has been found to be elevated in
      hypoxic cells in vitro and in erythrocytes and lymphocytes from patients who are
      septic. Loop diuretics decrease [Ca](i) in platelets from patients with
      hypertension and in red blood cells from normal volunteers. We report the results
      of a study designed to measure [Ca](i) in platelets from patients with acute
      renal failure (ARF) before and after the administration of loop diuretics.
      METHODS: Sixteen healthy adults and seven patients with ARF were enrolled into
      the study. Intraplatelet calcium was measured using a fluorescent probe (quin2).
      Patients with ARF all received intravenous (i.v.) dopamine, 2 microg/kg body
      weight, and 20% mannitol, 100 ml every 6 h and, in double-blind manner, either
      torasemide, frusemide, or placebo, 3 mg/kg body weight i.v. every 6 h. Data from
      subjects given either frusemide or torasemide have been considered together and
      termed the diuretic group. RESULTS: Basal levels of [Ca](i) in platelets from
      patients with ARF were significantly higher than in controls (126.9 +/-3 5.7
      nmol/l vs 85.7 +/- 22.2 nmol/l, P = 0.02), but were not affected by the
      administration of loop diuretic (126.9 +/- 35.7 nmol/l vs 165.9 +/- 49.7 nmol/l,
      P = 0.09, pre- vs post-diuretic). CONCLUSIONS: Intraplatelet calcium is raised in
      patients with ARF. Loop diuretics have no significant effect on intraplatelet
      calcium in these patients.

PMID- 11239031
TI  - Resting energy expenditure in pre-dialysis diabetic patients.
AB  - BACKGROUND: The metabolic derangements of diabetes mellitus (DM) associated with
      those of chronic renal failure (CRF) may interfere with the energy and protein
      balance of patients with both diseases. The aim of this study was to verify
      whether the resting energy expenditure (REE) of non-dialysis chronic renal
      failure diabetic patients differs from that of chronic renal failure patients
      without DM. METHODS: REE was measured by indirect calorimetry in 24 CRF diabetic
      patients (CRF diabetes group), matched for age, gender, and degree of renal
      impairment to 24 CRF patients without DM (CRF control group). RESULTS: The CRF
      diabetes group had a significantly higher REE (1538+/-230 kcal/day) than the CRF
      control group (1339+/-315 kcal/day, P = 0.009). This difference was maintained
      even when the REE was adjusted for lean body mass (LBM; 30.3+/-4.3 vs 26.3+/-5.4
      kcal/kg LBM/day, P = 0.004). Mean protein intake was significantly higher in the
      CRF diabetes than in the CRF control group (0.89+/-0.20 vs 0.76+/-0.25 g/kg/day,
      P = 0.02). Mean protein equivalent of nitrogen appearance (PNA) was also
      significantly higher in the CRF diabetes patients (1.21+/-0.31 vs 1.03+/-0.22
      g/kg/day, P = 0.02), reflecting a higher protein intake and/or elevated protein
      breakdown. Accordingly, REE was directly correlated with PNA mainly in the CRF
      diabetes group (r = 0.57, P < 0.003). CONCLUSION: Metabolic disturbances of
      poorly controlled DM may account for the higher REE observed in the CRF diabetes
      group. The role of the apparently higher protein breakdown in this increased REE
      remains to be clarified.

PMID- 11239032
TI  - Biomarkers of DNA damage in patients with end-stage renal disease: mitochondrial
      DNA mutation in hair follicles.
AB  - BACKGROUND: DNA damage was noted in patients with end-stage renal disease (ESRD).
      Mitochondrial DNA (mtDNA) mutations have been proposed as a genomic biomarker in
      the process of human ageing, degenerative diseases and carcinogenesis. METHODS:
      Polymerase chain reaction (PCR) techniques were applied to detect mtDNA deletions
      in hair follicles, an appendage of skin, from 162 patients with ESRD. RESULTS:
      The incidences of the 4977 bp deletion of mtDNA in hair follicles were found to
      increase with age in normal control and ESRD patients. As compared with normal
      subjects, ESRD patients had 3.5, 2.3, 2.7, 2.3 and 1.4 times higher incidences of
      the 4977 bp deletion of mtDNA in the age groups of 20-30, 31-40, 41-50, 51-60 and
      61-70 years, respectively. Moreover, the difference in the proportion of mtDNA
      with the 4977 bp deletion was statistically significant between ESRD patients and
      normal subjects >50 years of age. CONCLUSION: We suggest that the 4977 bp
      deletion of mtDNA in hair follicles may serve as one of the tissue biomarkers of
      genetic instability of the mitochondrial genome in ESRD patients.

PMID- 11239033
TI  - Differences in heart rate variability parameters during the post-dialytic period
      in type II diabetic and non-diabetic ESRD patients.
AB  - BACKGROUND: Heart rate variability parameters were evaluated in 10 healthy
      subjects, 10 type II diabetic patients and 20 end-stage renal disease (ESRD)
      patients (11 non-diabetic and nine type II diabetic) undergoing chronic
      haemodialysis. The study was divided in two phases. METHODS: In the first phase
      all subjects underwent electrocardiograph (ECG) recording under baseline
      conditions. In the second phase only ESRD patients underwent haemodialysis and
      ECG recording. On the day of dialysis and ECG recording the ECG recording was
      started 1 h before the haemodialysis session (pre-dialytic period), and continued
      throughout the dialysis (dialytic period), until the morning after (post-dialytic
      period). RESULTS: Compared with ESRD patients, non-ESRD patients showed the
      lowest cardiac sympathetic activity. Diabetic patients compared to non-diabetic
      patients showed a prevalence of cardiac sympathetic activity in the pre-dialytic
      period (P < 0.01). During the dialytic period in comparison with the pre-dialytic
      one, a further increase in cardiac sympathetic activity was observed in both
      diabetic and non-diabetic ESRD patients (P < 0.001). However, in the post
      dialysis period the cardiac autonomic nervous system activity remained at the pre
      dialytic condition in the diabetic group. In contrast, in the non-diabetic group
      the cardiac autonomic balance shifted towards a parasympathetic prevalence in the
      post-dialytic period (P < 0.01). In addition, a significant correlation was found
      between changes in heart rate variability and changes in plasma urea
      concentration in the non-diabetic group only (r = 0.65; P < 0.03). CONCLUSIONS:
      Non-insulin-dependent diabetic uraemic patients undergoing a chronic
      haemodialysis programme have a severe impairment of heart rate variability. This
      is probably due to autonomic neuropathy related to the effects of both diabetes
      and chronic uraemic conditions. In non-diabetic haemodialysis patients uraemia
      causes similar but reversible changes in heart rate variability compared with the
      changes caused by diabetes.

PMID- 11239034
TI  - Dehydroascorbic acid and oxidative stress in haemodialysis patients.
AB  - BACKGROUND: The amount of dehydroascorbic acid contained within total ascorbic
      acid (oxidized as well as non-oxidized forms) in plasma, hereafter referred to as
      the dehydroascorbic acid fraction, may be a measure of oxidative stress during
      haemodialysis. In the present study, we determined this fraction in chronic
      haemodialysis patients. METHODS: Using high performance liquid chromatography,
      dehydroascorbic acid and total ascorbic acid levels were measured in 80
      maintenance haemodialysis patients for a period of > 2 years as well as in 49
      controls, to examine a possible association of these compounds with clinical
      parameters and/or drugs taken by the patients. RESULTS: Dialysis patients who had
      an increased plasma urate level (P < 0.05) and had been taking allopurinol (P <
      0.05) or NSAID (non-steroid anti-inflammatory drugs) (P < 0.01), and dialysis
      patients who were younger (< or = 55 years), as compared with older dialysis
      patients (P < 0.01), were found to have a lower dehydroascorbic acid fraction by
      multivariate analysis. Mean plasma dehydroascorbic acid levels and
      dehydroascorbic acid fractions were significantly lower in the younger
      haemodialysis patients (4.8 +/- 0.7 micromol/l and 28.4 +/- 3.9%) than in healthy
      younger controls (13.3 +/- 1.1 micromol/l and 41.1 +/- 1.8%) (P < 0.0001 and P <
      0.01, respectively). Moreover, a correlation was found between plasma
      dehydroascorbic acid fraction and plasma lipid peroxide (r = 0.66, P < 0.01) in
      patients who had not been taking allopurinol and/or NSAID. CONCLUSION: We found
      that dehydroascorbic acid fraction was related to patients' age, plasma urate
      level and to taking allopurinol or NSAID. Dehydroascorbic acid fraction may be
      another indirect index of oxidative stress.

PMID- 11239035
TI  - Effect of 6 weeks of vitamin E administration on renal haemodynamic alterations
      following a single dose of neoral in healthy volunteers.
AB  - BACKGROUND: A single oral dose of cyclosporin-A (CsA) transiently reduces renal
      plasma flow (RPF) and glomerular filtration rate (GFR) in transplant patients
      and, in some patients, chronic administration of CsA leads to renal impairment
      and fibrosis. Based on experimental studies, several mediators including free
      radicals have been proposed to account for CsA-nephrotoxicity. We have previously
      reported that administration of the antioxidant vitamin E in a rat model of
      chronic CsA-nephrotoxicity reduces renal fibrosis and maintains renal function.
      METHODS: In the present study, the effect on renal haemodynamics of a single dose
      of the new oral formulation of CsA (neoral) was assessed before and after 6 weeks
      of vitamin E (800 IU/day, 2-fold increase in serum vitamin E). GFR (inulin
      clearance) and RPF (para-amino hippuric acid clearance) were measured before and
      after a single dose of 5 mg/kg of neoral in 12 healthy subjects under
      standardised conditions. RESULTS: Although the mean area under the curve of the
      CsA levels was 21% lower after the vitamin E period, the peak CsA level at 120
      min after neoral was similar both before and after vitamin E administration. At
      120 min after neoral, a transient reduction in RPF and GFR was noted both before
      and after vitamin E administration. The nadir of the reductions in RPF (-81 +/-27
      ml/min) and GFR (-14 +/- 6 ml/min) at 120 min compared with baseline tended to be
      lower before than after the treatment with vitamin E (-51 +/- 33 ml/min of RPF
      and -12 +/- 8, ml/min of GFR, respectively). Plasma and urine levels of F2
      isoprostanes (free radical-catalysed vasoconstrictive prostanoids (F2-iso) at 120
      min after the administration of neoral were not different from the pre-neoral
      levels. CONCLUSION: The findings demonstrate that a single oral dose of neoral
      causes transient, yet significant, reductions in RPF and GFR, and suggest that F2
      iso might not be involved in the CsA-induced acute renal vasoconstriction. The
      tendency for a lower reduction in RPF and GFR following CsA during the vitamin E
      period in healthy humans warrants additional studies in transplant patients.

PMID- 11239036
TI  - Difference in the homocysteine-lowering effect of folic acid in haemodialysis
      patients with and without occlusive vascular disease.
AB  - BACKGROUND: Hyperhomocysteinaemia has been identified as an independent
      cardiovascular risk factor and is found in more than 85% of patients on
      maintenance haemodialysis. Previous studies have shown that folic acid can lower
      circulating homocysteine in dialysis patients. We evaluated prospectively the
      effect of increasing the folic acid dosage from 1 to 6 mg per dialysis on plasma
      total homocysteine levels of haemodialysis patients with and without a history of
      occlusive vascular artery disease (OVD). METHODS: Thirty-nine stable patients on
      high-flux dialysis were studied. Their mean age was 63 +/-11 years and 17 (43%)
      had a history of OVD, either coronary and/or cerebral and/or peripheral occlusive
      disease. For several years prior to the study, the patients had received an oral
      post-dialysis multivitamin supplement including 1 mg of folic acid per dialysis.
      After baseline determinations, the folic acid dose was increased from 1 to 6
      mg/dialysis for 3 months. RESULTS: After 3 months, plasma homocysteine had
      decreased significantly by approximately 23% from 31.1 +/- 12.7 to 24.5 +/- 9
      micromol/l (P = 0.0005), while folic acid concentrations had increased from 6.5
      +/- 2.5 to 14.4+/-2.5 microg/l (P < 0.0001). However, the decrease of
      homocysteine was quite different in patients with and in those without OVD. In
      patients with OVD, homocysteine decreased only marginally by approximately 2.5%
      (from 29.0 +/- 10.3 to 28.3 +/- 8.4 micromol/l, P = 0.74), whereas in patients
      without OVD there was a significant reduction of approximately 34% (from 32.7+/
      14.4 to 21.6+/-8.6 micromol/l, P = 0.0008). Plasma homocysteine levels were
      reduced by > 15% in three patients (18%) in the group with OVD compared with 19
      (86%) in the group without OVD (P = 0.001), and by > 30% in none of the patients
      (0%) in the former group compared with 13 (59%) in the latter (P = 0.001).
      CONCLUSIONS: These results indicate that the homocysteine-lowering effect of
      folic acid administration appears to be less effective in haemodialysis patients
      having occlusive vascular disease than in those without evidence of such disease.

PMID- 11239037
TI  - Haemodialysis with the biocompatible high permeability AN-69 membrane does not
      alter plasma insulin-like growth factor-I and insulin-like growth factor binding
      protein-3.
AB  - BACKGROUND: Insulin-like growth factor-I (IGF-I) bioactivity has been reported to
      be decreased in maintenance haemodialysis patients and this may affect their
      nutritional status. Clearances of IGF-I and its binding proteins (IGFBPs) during
      haemodialysis sessions using a high permeability biocompatible membrane are
      unknown. METHODS: Five well nourished, non-diabetic adult patients were studied
      during one 4-h morning haemodialysis treatment using the high permeability
      biocompatible AN-69 dialyser. Blood was collected at the arterial and venous
      ports of the dialyser at 0, 1, 2 and 4 h of dialysis for haematocrit, plasma IGF
      I, IGFBP-3 and insulin measurements. IGF-I, IGFBP-3 and insulin concentrations
      were adjusted for haemoconcentration before comparisons were made. RESULTS: At
      the beginning of the dialysis session, plasma IGF-I, IGFBP-3 and insulin levels
      were within the normal range (297 +/- 47 ng/ml (mean+/-SEM), 4.3 +/- 0.6
      microg/ml and 11.8 +/- 3.4 microIU/ml, respectively). During the session, insulin
      tended to be cleared through the dialyser, whereas plasma IGF-I and IGFBP-3
      values did not vary significantly. CONCLUSION: Dialysis with the high
      permeability AN69 membrane did not alter the main blood compounds of the IGF
      system in well nourished chronic haemodialysis patients, and it is unlikely that
      the malnutrition frequently observed in such patients would result from
      alterations of the IGF system during haemodialysis.

PMID- 11239038
TI  - Prevention of haemodialysis-induced hypotension by biofeedback control of
      ultrafiltration and infusion.
AB  - BACKGROUND: Haemodialysis-induced hypotension is still a severe complication in
      spite of all the progress in haemodialysis treatment. Because of its
      multifactorial causes, haemodialysis-induced hypotension cannot be reliably
      prevented by conventional ultrafiltration and sodium profiling in open-loop
      systems, as they are unable to adapt themselves to actual decreases in blood
      pressure. METHODS: A blood-pressure-guided closed-loop system, for prevention of
      haemodialysis-induced hypotension by biofeedback-driven computer control of both
      ultrafiltration and saline infusion was clinically tested in 237 treatments of
      seven patients prone to hypotension. As medical knowledge on multifactorial
      causes of hypotension is characterized by a lack in deterministic knowledge,
      fuzzy logic and linguistic variables were used to involve clinical experience on
      hypotension phenomena in terms of fuzzy knowledge. Biofeedback control is based
      on frequent measurements of blood pressure at 5 min intervals. Blood pressure
      behaviour is described by linguistic variables and fuzzy sets. Adaptive rule
      bases were used for the simultaneous fuzzy control of both the ultrafiltration
      and infusion of hypertonic saline (20% NaCl). Proper adaptation of control
      features to patient's conditions was provided by the critical borderline
      pressure, which was set by the physician individually at the beginning of each
      treatment. During the initial and medium phases of the sessions, ultrafiltration
      rates up to 150% of the average rates were applied as long as decreases in blood
      pressure could be compensated by saline infusion. The surplus of ultrafiltrate
      volume was used for blood pressure stabilization in the final phase in most
      instances by low ultrafiltration rates. RESULTS: The advantages of biofeedback
      controlled haemodialysis were demonstrated by both decreasing the frequency of
      hypotonic episodes and by increasing or maintaining constant levels of systolic
      blood pressure during the final phase in 88% of treatments. As saline infusion
      was applied mainly in the initial and medium phases, blood sodium levels were not
      significantly higher at the end of the sessions, and interdialytic weight gain
      was not elevated. CONCLUSION: The application of fuzzy logic in the blood
      pressure-guided biofeedback control of ultrafiltration and sodium infusion during
      haemodialysis is able to minimize haemodialysis-induced hypotension.

PMID- 11239039
TI  - Comparison of infectious complications in peritoneal dialysis patients using
      either a twin-bag system or automated peritoneal dialysis.
AB  - BACKGROUND: Automated peritoneal dialysis (APD) and twin-bag (TB) systems are two
      major peritoneal dialysis (PD) modalities. Published data comparing the
      infectious complications of these modalities is limited. Subjects and methods.
      Ninety-five patients using APD (the APD group) and 117 patients using TB system
      (the TB group) were recruited. Among them, 35 patients used both modalities. The
      two groups' clinical characteristics, incidences of infectious complications, and
      the time intervals to first PD-related infection were compared. RESULTS: Clinical
      characteristics, incidence of exit-site infection (ESI), and time intervals to
      first ESI were similar in the TB and APD groups. The incidence of peritonitis in
      the APD group (1.22 episodes/100 patient-months) was significantly (P < 0.001)
      lower than that of the TB group (2.28 episodes/100 patient-months). Using the Cox
      proportional hazard model, APD was found to have a lower risk of peritonitis
      relative to TB systems, with marginal significance (RR 0.58, P = 0.051).
      CONCLUSION: APD was found to have a lower peritonitis rate than the TB system.
      Since reducing the peritonitis rate helps to maintain technical survival during
      PD, from this viewpoint, APD may be preferred for patients undergoing PD, unless
      contraindicated.

PMID- 11239040
TI  - Short-term efficiency and safety of gene delivery into canine kidneys.
AB  - BACKGROUND: Gene delivery of biologically active molecules to the kidney may have
      potential therapeutic applications in renal and cardiovascular diseases.
      Recombinant adenovirus is one of the most efficient vectors for in vivo gene
      delivery. However, in vivo toxicity at the site of administration has to be
      evaluated for the successful use of adenovirus-mediated gene transfer. The aim of
      this study was to document precisely the short-term safety of different routes of
      intra-renal adenoviral administration and to compare their transduction
      efficiency. METHODS: Dog puppies were injected with an adenoviral vector
      expressing the beta-galactosidase reporter gene in both kidneys via three
      different routes, i.e. intra-renal-ureteral route (IU) and intra-renal-arterial
      route with (IAC) or without (IA) clamping of the renal vein. Toxicity of viral
      administration was assayed on day 4 at both physiological and histological
      levels. Renal samples were monitored for the presence of nuclear beta
      galactosidase-expressing cells. RESULTS: All renal physiological parameters
      (glomerular filtration rate, effective renal plasma flow, and electrolyte
      excretion fractions) remained stable whatever the route of viral administration.
      No histological lesion was detected in any of the haematoxylin-eosin-stained
      kidney sections, and there was no evidence of ischaemia-reperfusion injury in the
      kidneys subjected to venous clamping. Efficient transgene expression was obtained
      in dog kidneys following IAC and IU injection of adenoviral vectors. Gene
      transfer via the IAC route induced gene expression predominantly in the cortical
      interstitial cells. Retrograde IU adenoviral injection resulted in reduced
      transduction efficiency compared with the IAC route, with transgene expression
      occurring mainly in the distal tubular and pyelic epithelial cells. CONCLUSIONS:
      The two major findings of this study were (i) the absence of acute histological
      and functional renal alteration following intra-arterial and intra-ureteral
      injections of adenoviral vectors in both kidneys of healthy dogs, and (ii) the
      efficiency of transgene expression with specific cellular targeting according to
      the route of administration.

PMID- 11239041
TI  - Premature ageing and glomerulonephritis.

PMID- 11239042
TI  - Controversies in organ donation: the altruistic living donor.

PMID- 11239043
TI  - Tumour-like calcinosis causing reversible tetraparesis in a patient on continuous
      ambulatory peritoneal dialysis.

PMID- 11239044
TI  - Acute graft dysfunction due to Kaposi sarcoma involving the bladder in a renal
      transplant recipient.

PMID- 11239045
TI  - Acute renal failure after an unusual mode of infection with falciparum malaria
      ('baggage malaria').

PMID- 11239046
TI  - A patient with neurological deficits and seizures after renal transplantation.

PMID- 11239047
TI  - Medullary sponge kidney--part of a congenital syndrome.

PMID- 11239048
TI  - Candidal endophthalmitis in a renal transplant patient.

PMID- 11239049
TI  - Bilateral venous thoracic outlet syndrome in a haemodialysis patient with long
      standing body building activities.

PMID- 11239050
TI  - Hypertriglyceridaemia and hyperuricaemia in IgA nephropathy.

PMID- 11239051
TI  - The impact of Trp64Arg mutation in the beta3-adrenergic receptor gene on
      haemodialysis patients.

PMID- 11239052
TI  - Lack of removal of nelfinavir during a haemodialysis session in an HIV-1 infected
      patient with hepatic and renal insufficiency.

PMID- 11239053
TI  - Immunological response to influenza vaccination in children with renal failure.

PMID- 11239054
TI  - Pharmacokinetics of ritonavir and nevirapine in peritoneal dialysis.

PMID- 11239055
TI  - Low-dose warfarin fails to prolong survival of dual lumen venous dialysis
      catheters.

PMID- 11239059
TI  - Ultrastructure of basement membranes of peritoneal capillaries in a chronic
      peritoneal infusion model in the rat.
AB  - BACKGROUND: Long-term peritoneal dialysis with glucose- based dialysis solutions
      has been associated with diabetiform alterations of peritoneal tissue. A
      peritoneal infusion model in the rat was developed to study the effect of chronic
      infusion of a glucose-based dialysis solution and an isotonic non-glucose
      solution on the ultrastructure of the basement membranes of peritoneal
      capillaries. The effect of ageing was also studied in an untreated control group.
      METHODS: A vascular access port (Rat-o-Port) with attached peritoneal catheter
      was implanted subcutaneously in the neck of nine male Wistar rats. The rats were
      divided randomly into three groups: the glucose group (n = 3) was infused daily
      for 20 weeks with 60 ml/kg body weight 3.86% glucose solution. A control group (n
      = 2) was infused daily for 20 weeks with 60 ml/kg body weight Ringer's lactate.
      The untreated control group (n = 4) was studied at the onset of the experiment
      and after 20 weeks. Omental tissue was obtained from each rat at the end of the
      experimental period for ultrastructural examination. RESULTS: Extensive
      lamination of basement membranes of omental capillaries was found in the glucose
      group. This was in contrast to the untreated control group where clear, single
      basement membranes were seen at the onset of the experiment and after 20 weeks.
      These latter findings were similar to those in the Ringer's lactate group.
      CONCLUSIONS: The chronic infusion model in the rat is suitable for the
      investigation of the effects on the ultrastructure of peritoneal capillaries of
      chronic exposure to dialysis fluids. The duplications of basement membranes of
      omental capillaries found in the glucose group show a striking resemblance to
      those found in long-term peritoneal dialysis patients. This suggests a role for
      glucose in the development of peritoneal ultrastructural alterations found in
      long-term peritoneal dialysis.

PMID- 11239060
TI  - Multidirectional approach to study peritoneal dialysis fluid biocompatibility in
      a chronic peritoneal dialysis model in the rat.
AB  - BACKGROUND: Peritoneal dialysis causes the functional and morphological changes
      in the peritoneum that result from the bioincompatibility of dialysis solutions.
      We present a model of chronic peritoneal dialysis in the rat that can be used for
      testing the biocompatibility of dialysis fluids. Methods and Results. Long-term
      exposure of the peritoneum to dialysis solutions can be performed in rats with
      implanted peritoneal catheters. Sampling of the dialysate allows the evaluation
      of intraperitoneal inflammation by examining cell differential and dialysate
      cytokine levels. Peritoneal permeability can be evaluated at designed time
      intervals with the peritoneal equilibration test (PET). At the end of dialysis,
      peritoneal histology is studied with light and electron microscopy. CONCLUSIONS:
      Such a multidirectional approach is an effective way to test biocompatibility of
      dialysis solutions.

PMID- 11239061
TI  - Intravital microscopy: an integrated evaluation of peritoneal function and
      structure.
AB  - Peritoneal dialysis (PD) solutions may affect various aspects of peritoneal
      function and structure. The present communication describes the application of an
      intravital microscopy technique for the study of peritoneal pathophysiology. The
      technique allows the in vivo measurement of peritoneal blood flow rate,
      microvascular permeability to macromolecules, leukocyte-endothelial interactions,
      microvascular density and lymph vessel kinetics. The off-line coupling to a
      computer-assisted image analysis system permits the rapid quantitation and
      integrated evaluation of these different parameters. The model may be an
      attractive tool for the study of the pathophysiological consequences of acute or
      long-term dialysate exposure, as well as for the development and evaluation of
      novel PD solutions.

PMID- 11239062
TI  - Nitric oxide-related experiments on peritoneal solute transport in the rabbit.
AB  - BACKGROUND: It is unclear whether nitric oxide (NO) is important in regulating
      peritoneal transport during non-infected peritoneal dialysis. METHODS: In 13
      rabbits, 250 mg/l L-arginine, a substrate for NO synthesis, was added to a 3.86%
      glucose dialysis solution. N:(G)-monomethyl-L-arginine (L-NMMA) 25 mg/1, an
      inhibitor of NO synthase, was added to the dialysate in 10 rabbits. Standard
      peritoneal permeability analyses in rabbits were used to analyse the effects of
      these interventions on solute transport during 1-h dwells. The addition of 4.5
      mg/l nitroprusside to the dialysate in five rabbits was used for validation of
      this model. RESULTS: Nitroprusside caused an 86% (48-233%) increase in albumin
      clearance, which is similar to the nitroprusside-induced increase found in humans
      (70%). Contrary to human studies, no effect was found on the mass transfer area
      coefficient (MTAC) of urea and creatinine, or on glucose absorption. L-Arginine
      did not affect either the MTAC of urea and creatinine, or the absorption of
      glucose. Peritoneal albumin clearance increased 18% (-24 to 609%). This resembles
      the NO-mediated effects of nitroprusside. Addition of L-NMMA caused no change in
      the solute transport rate. CONCLUSION: The rabbit dialysis model can be used for
      analysing the effects of interventions on peritoneal permeability
      characteristics, although the rabbit peritoneal membrane is probably less
      sensitive to NO compared with that of humans. L-Arginine-induced effects are
      similar to those of nitroprusside, which suggests that these effects possibly are
      mediated by NO. As L-NMMA did not affect peritoneal transport, it is unlikely
      that NO is involved in the regulation of peritoneal permeability in rabbits.

PMID- 11239063
TI  - The rabbit model in evaluating the biocompatibility in peritoneal dialysis.
AB  - Rat and rabbit are the most common animal models for peritoneal dialysis. Rats
      are cheap and easy to keep. Rabbits allow dialysis to be performed for longer
      periods and in a way very similar to that used in human patients. Recent progress
      in histomorphometry enables accurate comparison of the biocompatibility of
      different peritoneal dialysis solutions. Preliminary data in the rabbit indicate
      that peritoneal dialysis is associated with a change in both the number and size
      of milky spots, which are peritoneal corpuscles involved in peritoneal defence.

PMID- 11239064
TI  - Ex vivo and in vivo gene transfer to the peritoneal membrane in a rat model.
AB  - The efficacy of peritoneal dialysis (PD) depends on preserving the structural
      integrity and dialysing capacity of the peritoneal membrane. Membrane structure
      and function can change on PD, resulting in decreased membrane performance and
      possible discontinuation of PD as a treatment modality. We hypothesized that a
      gene therapy strategy might be an innovative and promising approach to
      maintaining membrane integrity and dialysing capacity in the PD population. We
      have characterized two methods of genetic modification of the peritoneal membrane
      in a rat model to test the feasibility of this approach. In ex vivo gene
      transfer, mesothelial cells are isolated from the peritoneal membrane,
      genetically modified in culture and subsequently re-implanted back onto the
      peritoneal membrane of syngeneic recipients. In in vivo gene transfer, genetic
      modification of the membrane is accomplished in situ through adenovirus-mediated
      delivery of the genetic material into the peritoneal cavity. The peritoneal
      membrane can be genetically modified to produce factors that may be of
      therapeutic value in maintaining the fibrinolytic balance in the peritoneal
      cavity, moderating peritoneal inflammation, and studying the development of
      peritoneal fibrosis. These models provide a basis for studying the contribution
      of specific molecules to peritoneal membrane physiology. Optimally, they will be
      paired with other PD-relevant model systems to understand peritoneal physiology,
      identify ways to prevent membrane damage, and maintain dialysing performance.
      While gene transfer can be used as a tool to understand the individual roles of
      factors or pathways in peritoneal membrane physiology, it can also be developed
      as a therapy platform for improving membrane characteristics and enhancing the
      therapy of peritoneal dialysis.

PMID- 11239065
TI  - Effects of intraperitoneal heparin on peritoneal transport in a chronic animal
      model of peritoneal dialysis.
AB  - BACKGROUND: Heparin has anti-inflammatory effects and is often added to the
      peritoneal dialysis fluid to prevent fibrin formation. Conjugation of heparin to
      the surface of biomaterials has been shown to improve its biocompatibility. In
      this study, we describe for the first time an experimental chronic peritoneal
      dialysis model with repeated dwell studies in non-uraemic rats and evaluate the
      effect of addition of heparin to glucose-based peritoneal dialysis fluid on
      peritoneal fluid and solute transport. METHODS: Wistar male rats, weighing 340+/
      15 g, with implanted peritoneal catheters were infused during 1 month, twice per
      day with 20 ml of Dianeal 1.36%+antibiotics (AB; n = 10) or Dianeal
      1.36%+antibiotics+heparin 2500 U/l (HAB; n = 9). After 10 (DS 1) and 30 days (DS
      2), a dwell study was performed in rats with free access to drinking water, by
      infusing 30 ml of Dianeal 3.86%. Dialysate samples were obtained at 0, 2, 30, 60,
      120 and 240 min. Blood samples were drawn before and at the end of the dwell.
      Radiolabelled serum albumin was used as macromolecular volume marker. RESULTS:
      Peritoneal volumes during DS 1 were significantly greater for the HAB group as
      compared with the AB group. No differences in ultrafiltration were found during
      DS 2 for HAB vs AB. However, peritoneal volumes were significantly higher for DS
      2 compared with DS 1 in the AB group. The amount of glucose absorbed over time
      did not differ between the solutions, while fluid absorption tended to be lower
      in the HAB group. CONCLUSIONS: Heparin may improve peritoneal fluid transport
      possibly due to better healing and reduced peritoneal inflammation as shown in
      this novel animal model of chronic peritoneal dialysis with repeated dwell
      studies.

PMID- 11239066
TI  - Rat models in peritoneal dialysis.
AB  - BACKGROUND: It is widely accepted that the currently used dialysis solutions are
      not biocompatible with the peritoneal membrane. Therefore, animal studies have
      been performed to study different aspects of peritoneal dialysis. However,
      representative models mimicking the human situation are not yet available.
      METHODS: The effect of a single injection of peritoneal dialysis (PD) fluid on
      the cellular composition was studied. Thereafter, the effect of a single
      injection of PD fluid on bacterial clearing was tested over time. Finally, an in
      vivo rat model was established to study the effects of long-term exposure to PD
      fluid on the peritoneal membrane and the local host defence (peritoneal cells).
      RESULTS: In the rat model, long-term daily exposure is possible. The 'drop-out'
      after 9-10 weeks on the most commonly used PD fluid Dianeal 3.86%, however, is
      approximately 50% due to omental wrapping. In the remaining study group, large
      differences were observed (as compared with controls), especially with respect to
      morphological parameters. CONCLUSIONS: The rat peritoneal continuous exposure
      model seems to have potential for intervention studies, since it uses no
      additions, no antibiotics and no omentomectomy, and gives continuous long-term
      exposure to PD fluid. However, problems still remain: 'drop-out' is quite often
      seen and this non-uraemic exposure model does not totally mimic the situation
      present in continuous ambulatory PD patients.

PMID- 11239067
TI  - Regulation of NO synthase isoforms in the peritoneum: implications for
      ultrafiltration failure in peritoneal dialysis.
AB  - BACKGROUND: Ultrafiltration (UF) failure often complicates peritoneal dialysis
      (PD). At least two molecules might be involved in UF failure: aquaporin-1 (AQP1),
      a water channel thought to be the ultra small pore of the peritoneal membrane
      (PM), and nitric oxide (NO), which might regulate effective peritoneal surface
      area and microvascular permeability. METHODS: The contributions of AQP1 and NO in
      UF failure were evaluated by combining different experimental approaches.
      Specific antibodies were used to investigate the expression (immunoblotting) and
      localization (immunostaining) of AQP1 and NO synthase (NOS) isoforms in the
      peritoneum, in correlation with: (i) morphometric analyses; (ii) the l-citrulline
      assay, which specifically measures NOS enzymatic activities; and (iii)
      permeability parameters across the PM. RESULTS: AQP1 is located in the
      endothelium lining peritoneal capillaries, and its expression is remarkably
      stable in samples ranging from normal to highly inflamed peritoneum and even when
      transcellular water permeability is absent (loss of sodium sieving). A
      significant NOS activity, mediated by specific NOS isoforms, can be assayed in
      the peritoneum. The NOS activity significantly increases in conditions such as
      peritonitis and long-term PD, and this increase is mirrored by up-regulation of
      NOS isoforms, as well as angiogenesis and increased endothelial area.
      CONCLUSIONS: These data suggest that the NO-mediated increase in effective
      peritoneal surface area, followed by a dissipation of the osmotic gradient, is a
      major mechanism accounting for the loss of UF in PD. Other biological
      consequences of increased NO levels in the peritoneum might include initiation of
      angiogenesis or modification of functionally important proteins such as AQP1.

PMID- 11239068
TI  - Effect of PD fluid instillation on the peritonitis-induced influx and bacterial
      clearing capacity of peritoneal cells.
AB  - BACKGROUND: The commonly used peritoneal dialysis fluids contain glucose as the
      osmotic agent. Heat sterilization leads to the formation of glucose degradation
      products which contribute, together with glucose, to the formation of advanced
      glycation end-products (AGEs). AGEs have been shown to be present in the
      peritoneal cavity. Methods have been developed to minimize the amount of glucose
      degradation products in peritoneal dialysis fluids. In a rat peritoneal dialysis
      model, we compare the effect of a commonly used peritoneal dialysis fluid,
      Gambrosol, with a newly developed peritoneal dialysis fluid, PD-Bio, on the
      influx and functional capacity of the peritoneal cells after 2 weeks of
      peritoneal dialysis fluid instillation. METHODS: Three groups of animals were
      used: rats received daily infusion with 15 ml of either 4% Gambrosol (group 1) or
      4% PD-Bio (group 2), and a control group of animals did not receive fluid (group
      3). After 2 weeks of PD fluid instillation, all the animals were injected with a
      0.5 ml suspension containing 3x10(8) colony-forming units of Staphylococcus
      aureus. The in vivo bacterial clearing capacity was determined after 15 h.
      RESULTS: A statistically significant higher leukocyte influx was found in the
      control group compared with both PD fluid-injected groups. No statistical
      differences in bacterial clearing were observed among the three groups, although
      the number of bacteria recovered from the PD-Bio group tended to be lower than
      that from the Gambrosol group. Moreover, in both PD fluid instillation groups,
      the bacteria tended to be cleared more slowly compared with the control group.
      The number of mesothelial cells in the PD fluid groups was significantly greater
      than in the control group. CONCLUSION: No differences were observed in bacterial
      clearing capacity, leukocyte influx and mesothelial cell number after a 2 week
      exposure of the peritoneal cavity to Gambrosol vs PD-Bio.

PMID- 11239072
TI  - Serial order effects in spelling errors: evidence from two dysgraphic patients.
AB  - This study reports data from two dysgraphic patients, TH and PB, whose errors in
      spelling most often occurred in the final part of words. The probability of
      making an error increased monotonically towards the end of words. Long words were
      affected more than short words, and performance was similar across different
      output modalities (writing, typing and oral spelling). This error performance was
      found despite the fact that both patients showed normal ability to repeat the
      same words orally and to access their full spelling in tasks that minimized the
      involvement of working memory. This pattern of performance locates their deficit
      to the mechanism that keeps graphemic representations active for further
      processing, and shows that the functioning of this mechanism is not controlled or
      "refreshed" by phonological (or articulatory) processes. Although the overall
      performance pattern is most consistent with a deficit to the graphemic buffer,
      the strong tendency for errors to occur at the ends of words is unlike many
      classic "graphemic buffer patients" whose errors predominantly occur at word
      medial positions. The contrasting patterns are discussed in terms of different
      types of impairment to the graphemic buffer.

PMID- 11239073
TI  - Developmental prosopagnosia: should it be taken at face value?
AB  - This study presents a rare case of developmental prosopagnosia. Structural
      magnetic resonance imaging (MRI) revealed no overt brain abnormalities. EP's
      basic visual skills and visual memory were intact, as was his ability to judge
      age, sex and expression from faces, identify facial parts, and make face/non-face
      decisions. EP was impaired at recognizing famous and very familiar faces and
      describing visual images of famous faces. He also displayed an anterograde memory
      impairment for recently studied faces, and performed poorly on tests of
      unfamiliar face matching, most notably for chimeric faces. It is suggested that
      EP may be deficient at encoding configural representations of faces. EP appears
      to have a "pure" (i.e. specific to faces) prosopagnosia, as he shows normal
      object recognition from unusual viewpoints, good gestalt completion for objects,
      but not for faces, normal visual imagery for objects but not for faces, a
      disruption of the inversion effect for faces but not for houses, and performs
      within the normal range on tests of within-category discriminations, even with
      unique exemplars of object categories such as famous buildings.

PMID- 11239074
TI  - The classification, genetics and neuropathology of frontotemporal dementia.
      Introduction to the special topic papers: Part I.
AB  - Interest in the neuropsychology and neuropsychiatry of frontotemporal dementia
      (FTD) has escalated in the past decade, as evidenced by the accompanying 10
      special topic papers from research groups in the UK, France, North America and
      Australia addressing a wide range of theoretical and clinical issues. The first
      part of this review deals with the confusing terminologies that have been used in
      the area and argues for the retention of the term FTD as the general clinical
      label, with further subcategorization into the three principal clinical syndromes
      seen at presentation: frontal variant FTD (often called dementia of frontal
      type), semantic dementia and progressive non-fluent aphasia. Each of these
      syndromes has a characteristic profile of presenting clinical features, but may
      be accompanied by any one of five types of non-Alzheimer pathological change.
      There have also been significant advances in the genetics of FTD with the
      identification of tau gene mutations on chromosome 17 in some familial cases. The
      remarkable story of the discovery of these, the tau gene mutations, is briefly
      described. Part II of this review (Hodges and Miller, 2001) sets the special
      issue papers within the context of advances in the neuropsychology of frontal
      variant FTD and semantic dementia.

PMID- 11239075
TI  - Different patterns of autobiographical memory loss in semantic dementia and
      medial temporal lobe amnesia: a challenge to consolidation theory.
AB  - Temporally graded retrograde memory loss, with a disproportionate impairment of
      recent relative to remote memories, is considered a hallmark of medial temporal
      lobe amnesia. According to consolidation theory, the hippocampal complex, which
      includes the hippocampal formation, parahippocampal gyrus, the entorhinal and
      perirhinal cortex, plays a time-limited role in memory, needed only until
      consolidation in the neocortex is complete (Squire, Psychological Review 1992;
      99: 195-231). Recent support for this theory comes from findings of a reverse
      gradient in people with semantic dementia with neocortical degeneration but a
      relatively preserved hippocampal complex (Hodges and Graham, Neuropsychologia
      1998; 36: 803-25). Consolidation theory is challenged by evidence that remote
      autobiographical memory is not always spared in amnesia (Nadel and Moscovitch,
      Current Opinion in Neurobiology 1997; 7: 217-27) and that semantic memory becomes
      highly personalized in semantic dementia (Snowden et al., Memory 1995; 3: 225
      46). According to Nadel and Moscovitch, the hippocampal complex is needed to
      retain and retrieve detailed memories of autobiographical episodes no matter how
      old they are. To test consolidation theory against the opposing view, we
      investigated the role of the hippocampal complex in recent and remote
      autobiographical and personal semantic memory by contrasting the memory of a
      semantic dementia patient, EL, with that of an amnesic patient, KC, using family
      photographs as recall cues. KC demonstrated a complete loss of autobiographical
      episodes with a sparing of autobiographical facts; EL demonstrated well-preserved
      memory for episodes with a reverse gradient for personally relevant names. The
      influence of autobiographical significance on memory for names of public figures
      was examined further by comparing the effect that familiarity and recollection
      had on recognition of names of famous people and famous places. EL's memory was
      influenced by autobiographical significance, whereas KC's was not. We propose
      that the hippocampal complex plays a permanent role in the storage and retrieval
      of autobiographical episodes and that autobiographical significance may affect
      semantic representations.

PMID- 11239076
TI  - Severe anterograde amnesia with extensive hippocampal degeneration in a case of
      rapidly progressive frontotemporal dementia.
AB  - Frontotemporal dementia (FTD) is usually characterized as a spectrum of
      relatively slowly progressive disorders with largely focal frontal or temporal
      presentations. The development of clinical and research criteria for
      discriminating FTD from Alzheimer's disease has relied, in part, on the relative
      preservation of episodic memory in FTD. We present a patient with FTD who, in
      addition to the more typical behavioural and language deficits, had a profound
      anterograde amnesia at the time of diagnosis. Neuroimaging confirmed atrophy of
      frontal and temporal lobes bilaterally, most marked in the anterior left temporal
      region. At post-mortem, non-Alzheimer pathology resulting in devastating cell
      loss was revealed in the hippocampi, as well as in the frontal and temporal
      cortex, thus providing neuroanatomical corroboration of the episodic memory
      deficit. Progression of the disease was extraordinarily rapid, with just 2 years
      between reported onset and time of death. This case demonstrates that the pattern
      of FTD may include severe anterograde amnesia as a prominent and early
      consequence of the disease.

PMID- 11239077
TI  - The selective preservation of colour naming in semantic dementia.
AB  - This paper documents a series of seven patients with semantic dementia who showed
      a selective preservation in colour naming. This was in the context of a pervasive
      impairment in naming nouns across a wide range of other semantic categories. To
      our knowledge, this is the first series of patients with semantic dementia
      documenting a selective preservation of colour naming. These findings are
      discussed in the light of current theoretical accounts of category-specific
      effects and the possible contribution of imageability to this selective
      preservation of colours.

PMID- 11239078
TI  - Repeating without semantics: surface dysphasia?
AB  - We describe our investigations of MNA, who had a progressive, severe and global
      loss of semantic knowledge (semantic dementia). Her verbal vocabulary was
      restricted to a few common words and she was also unable to recognize common
      objects from sight. By contrast, she had a well-preserved digit span (7-8
      digits). In this series of experiments, we focused on her ability to repeat lists
      and sentences in which familiarity, meaningfulness, morphology and syntactic
      structure were manipulated. In list repetition tasks, we found that MNA showed a
      reliable effect of phonological similarity, word frequency and stimulus
      lexicality, but was unaffected by linguistic complexity, word length, semantic
      coherence or the status of individual stimuli as "known" or "unknown". In
      sentence repetition, her performance was not influenced by any semantic
      variables. However, there was a substantial effect of the frequency of the
      constituent vocabulary, even for words outside the range of her retained
      vocabulary. The influence of syntax was restricted to minor effects of
      morphology. The phonemes of syllables and the syllables of words are bound by
      their co-occurrence rather than their meaning. We conclude that the phonological
      representation of words is functionally independent of the semantic system.

PMID- 11239079
TI  - Superior written over spoken picture naming in a case of frontotemporal dementia.
AB  - Two main hypotheses have been proposed regarding the role of phonology in written
      word production. According to the phonological mediation hypothesis, the
      retrieval of the lexical phonological representation of a word is an obligatory
      prerequisite to the retrieval of its spelling. Therefore, deficits to the
      phonological lexicon should affect both spoken and written picture naming. In
      contrast, the orthographic autonomy hypothesis posits that the lexical
      orthographic representations of words can be accessed without any necessary
      phonological mediation. In support of this view, cases of preserved written
      naming despite impaired lexical phonology have been reported following brain
      damage. In this report, we replicate this basic pattern of performance in case
      YP, a 60-year-old woman with a pattern of frontotemporal dementia. As her disease
      progressed, YP's ability to write down the names of pictures remained very good
      despite a severe decline in oral naming. Further testing indicated that this
      deficit was not primarily due to an articulatory or post-lexical phonological
      deficit. YP's case provides strong additional support for the orthographic
      autonomy hypothesis. The significance of this case with respect to the
      characterization of dementia syndromes is discussed.

PMID- 11239080
TI  - WAM: an improved algorithm for modelling antibodies on the WEB.
AB  - An improved antibody modelling algorithm has been developed which incorporates
      significant improvements to the earlier versions developed by Martin et al.
      (1989, 1991), Pedersen et al. (1992) and Rees et al. (1996) and known as AbM
      (Oxford Molecular). The new algorithm, WAM (for Web Antibody Modelling), has been
      launched as an online modelling service and is located at URL
      http://antibody.bath.ac.uk. Here we provide a summary only of the important
      features of WAM. Readers interested in further details are directed to the
      website, which gives extensive background information on the methods employed. A
      brief description of the rationale behind some of the newer methodology
      (specifically, the knowledge-based screens) is also given.

PMID- 11239081
TI  - Experimental evidence for the correlation of bond distances in peptide groups
      detected in ultrahigh-resolution protein structures.
AB  - The structural analysis of a deamidated derivative of ribonuclease A, determined
      at 0.87 A resolution, reveals a highly significant negative correlation between
      CN and CO bond distances in peptide groups. This trend, i.e. the CO bond
      lengthens when the CN bond shortens, is also found in seven out of eight protein
      structures, determined at ultrahigh resolution (<0.95 A). In five of them the
      linear correlation is statistically significant at the 95% confidence level. The
      present findings are consistent with the traditional view of amide resonance and,
      although already found in small peptide structures, they represent a new and
      important result. In fact, in a protein structure the fine details of the peptide
      geometry are only marginally affected by the crystal field and they are mostly
      produced by intramolecular and solvent interactions. The analysis of very high
      resolution protein structures can reveal subtle information about local
      electronic features of proteins which may be critical to folding, function or
      ligand binding.

PMID- 11239082
TI  - The ups and downs of protein topology; rapid comparison of protein structure.
AB  - Protein topology can be described at different levels. At the most fundamental
      level, it is a sequence of secondary structure elements (a "primary topology
      string"). Searching predicted primary topology strings against a library of
      strings from known protein structures is the basis of some protein fold
      recognition methods. Here a method known as TOPSCAN is presented for rapid
      comparison of protein structures. Rather than a simple two-letter alphabet
      (encoding strand and helix), more complex alphabets are used encoding direction,
      proximity, accessibility and length of secondary elements and loops in addition
      to secondary structure. Comparisons are made between the structural information
      content of primary topology strings and encodings which contain additional
      information ("secondary topology strings"). The algorithm is extremely fast, with
      a scan of a large domain against a library of more than 2000 secondary structure
      strings completing in approximately 30 s. Analysis of protein fold similarity
      using TOPSCAN at primary and secondary topology levels is presented.

PMID- 11239083
TI  - Evolutionary trace analysis of TGF-beta and related growth factors: implications
      for site-directed mutagenesis.
AB  - The TGF-beta family of growth factors contains a large number of homologous
      proteins, grouped in several subfamilies on the basis of sequence identity. These
      subgroups can be combined into three broader groups of related cytokines, with
      marked specificities for their cellular receptors: the TGF-betas, the activins
      and the BMPs/GDFs. Although structural information is available for some members
      of the TGF-beta family, very little is known about the way in which these growth
      factors interact with the extra-cellular domains of their multiple cell surface
      receptors or with the specific protein inhibitors thought to modulate their
      activity. In this paper, we use the evolutionary trace method [Lichtarge et al.
      (1996) J. Mol. Biol., 257, 342-358] to locate two functional patches on the
      surface of TGF-beta-like growth factors. The first of these is centred on a
      conserved proline (P(36) in TGF-betas 1-3) and contains two amino acids which
      could account for the receptor specificity of TGF-betas (H(34) and E(35)). The
      second patch is located on the other side of the growth factor protomer and
      surrounds a hydrophobic cavity, large enough to accommodate the side chain of an
      aromatic residue. In addition to two conserved tryptophans at positions 30 and
      32, the main protagonists in this potential binding interface are found at
      positions 31, 92, 93 and 98. Several mutagenesis studies have highlighted the
      importance of the C-terminal region of the growth factor molecule in TGF-betas
      and of residues in activin A equivalent to positions 31 and 94 of the TGF-betas
      for the binding of type II receptors to these ligands. These data, together with
      our improved knowledge of possible functional residues, can be used in future
      structure-function analysis experiments.

PMID- 11239084
TI  - PoPMuSiC, an algorithm for predicting protein mutant stability changes:
      application to prion proteins.
AB  - A novel tool for computer-aided design of single-site mutations in proteins and
      peptides is presented. It proceeds by performing in silico all possible point
      mutations in a given protein or protein region and estimating the stability
      changes with linear combinations of database-derived potentials, whose
      coefficients depend on the solvent accessibility of the mutated residues. Upon
      completion, it yields a list of the most stabilizing, destabilizing or neutral
      mutations. This tool is applied to mouse, hamster and human prion proteins to
      identify the point mutations that are the most likely to stabilize their cellular
      form. The selected mutations are essentially located in the second helix, which
      presents an intrinsic preference to form beta-structures, with the best mutations
      being T183-->F, T192-->A and Q186-->A. The T183 mutation is predicted to be by
      far the most stabilizing one, but should be considered with care as it blocks the
      glycosylation of N181 and this blockade is known to favor the cellular to scrapie
      conversion. Furthermore, following the hypothesis that the first helix might
      induce the formation of hydrophilic beta-aggregates, several mutations that are
      neutral with respect to the structure's stability but improve the helix
      hydrophobicity are selected, among which is E146-->L. These mutations are
      intended as good candidates to undergo experimental tests.

PMID- 11239085
TI  - Characterization of the beta-lactam binding site of penicillin acylase of
      Escherichia coli by structural and site-directed mutagenesis studies.
AB  - The binding of penicillin to penicillin acylase was studied by X-ray
      crystallography. The structure of the enzyme-substrate complex was determined
      after soaking crystals of an inactive betaN241A penicillin acylase mutant with
      penicillin G. Binding of the substrate induces a conformational change, in which
      the side chains of alphaF146 and alphaR145 move away from the active site, which
      allows the enzyme to accommodate penicillin G. In the resulting structure, the
      beta-lactam binding site is formed by the side chains of alphaF146 and betaF71,
      which have van der Waals interactions with the thiazolidine ring of penicillin G
      and the side chain of alphaR145 that is connected to the carboxylate group of the
      ligand by means of hydrogen bonding via two water molecules. The backbone oxygen
      of betaQ23 forms a hydrogen bond with the carbonyl oxygen of the phenylacetic
      acid moiety through a bridging water molecule. Kinetic studies revealed that the
      site-directed mutants alphaF146Y, alphaF146A and alphaF146L all show significant
      changes in their interaction with the beta-lactam substrates as compared with the
      wild type. The alphaF146Y mutant had the same affinity for 6-aminopenicillanic
      acid as the wild-type enzyme, but was not able to synthesize penicillin G from
      phenylacetamide and 6-aminopenicillanic acid. The alphaF146L and alphaF146A
      enzymes had a 3-5-fold decreased affinity for 6-aminopenicillanic acid, but
      synthesized penicillin G more efficiently than the wild type. The combined
      results of the structural and kinetic studies show the importance of alphaF146 in
      the beta-lactam binding site and provide leads for engineering mutants with
      improved synthetic properties.

PMID- 11239086
TI  - The functional implications of the dimerization of the catalytic subunits of the
      mammalian brain platelet-activating factor acetylhydrolase (Ib).
AB  - The mammalian brain contains significant amounts of the cytosolic isoform Ib of
      the platelet-activating factor acetylhydrolase (PAF-AH), a unique type of PLA2.
      This oligomeric protein complex contains three types of subunits: two homologous
      (63% identity) 26 kDa catalytic subunits (alpha(1) and alpha(2)) which harbor all
      the PAF-AH activity, and the 45 kDa beta-subunit (LIS1), a product of the causal
      gene for Miller-Dieker lissencephaly. During fetal development, the
      preferentially expressed alpha(1)-subunit forms a homodimer, which binds to a
      homodimer of LIS1, whereas in adult organisms alpha(1)/alpha(2) and
      alpha(2)/alpha(2) dimers, also bound to dimeric LIS1, are the prevailing species.
      The consequences of this "switching" are not understood, but appear to be of
      physiological significance. The alpha(1)- and alpha(2)-subunits readily associate
      with very high affinity to form homodimers. The nature of the interface has been
      elucidated by the 1.7 A resolution crystal structure of the alpha(1)/alpha(1)
      homodimer (Ho et al., 1997). Here, we examined the functional consequences of the
      dimerization in both types of alpha-subunits. We obtained monomeric protein in
      the presence of high concentrations (>50 mM) of Ca2+ ions, and we show that it is
      catalytically inactive and less stable than the wild type. We further show that
      Arg29 and Arg22 in one monomer contribute to the catalytic competence of the
      active site across the dimer interface, and complement the catalytic triad of
      Ser47, Asp192 and His195, in the second monomer. These results indicate that the
      brain PAF-acetylhydrolase is a unique PLA2 in which dimerization is essential for
      both stability and catalytic activity.

PMID- 11239087
TI  - Module shuffling of a family F/10 xylanase: replacement of modules M4 and M5 of
      the FXYN of Streptomyces olivaceoviridis E-86 with those of the Cex of
      Cellulomonas fimi.
AB  - To facilitate an understanding of structure-function relationships, chimeric
      xylanases were constructed by module shuffling between the catalytic domains of
      the FXYN from Streptomyces olivaceoviridis E-86 and the Cex from Cellulomonas
      fimi. In the family F/10 xylanases, the modules M4 and M5 relate to substrate
      binding so that modules M4 and M5 of the FXYN were replaced with those of the Cex
      and the chimeric enzymes denoted FCF-C4, FCF-C5 and FCF-C4,5 were constructed.
      The k(cat) value of FCF-C5 for p-nitrophenyl-beta-D-cellobioside was similar to
      that of the FXYN (2.2 s(-1)); however, the k(cat) value of FCF-C4 for p
      nitrophenyl-beta-D-cellobioside was significantly higher (7.0 s(-1)). The loss of
      the hydrogen bond between E46 and S22 or the presence of the I49W mutation would
      be expected to change the position of Q88, which plays a pivotal role in
      discriminating between glucose and xylose, resulting in the increased k(cat)
      value observed for FCF-C4 acting on p-nitrophenyl-beta-D-cellobioside since
      module M4 directly interacts with Q88. To investigate the synergistic effects of
      the different modules, module M10 of the FCF-C4 chimera was replaced with that of
      the Cex. The effects of replacement of module M4 and M10 were almost additive
      with regard to the K:(m) and k(cat) values.

PMID- 11239088
TI  - Efficient cleavage of RNA at high temperatures by a thermostable DNA-linked
      ribonuclease H.
AB  - To construct a DNA-linked RNase H, which cleaves RNA site-specifically at high
      temperatures, the 15-mer DNA, which is complementary to the polypurine-tract
      sequence of human immunodeficiency virus-1 RNA (PPT-RNA), was cross-linked to the
      unique thiol group of Cys135 in the Thermus thermophilus RNase HI variant. The
      resultant DNA-linked enzyme (d15-C135/TRNH), as well as the d15-C135/ERNH, in
      which the RNase H portion of the d15-C135/TRNH is replaced by the Escherichia
      coli RNase HI variant, cleaved the 15-mer PPT-RNA site-specifically. The mixture
      of the unmodified enzyme and the unlinked 15-mer DNA also cleaved the PPT-RNA but
      in a less strict manner. In addition, this mixture cleaved the PPT-RNA much less
      effectively than the DNA-linked enzyme. These results indicate that the cross
      linking limits but accelerates the interaction between the enzyme and the DNA/RNA
      substrate. The d15-C135/TRNH cleaved the PPT-RNA more effectively than the d15
      C135/ERNH at temperatures higher than 50 degrees C. The d15-C135/TRNH showed the
      highest activity at 65 degrees C, at which the d15-C135/ERNH showed little
      activity. Such a thermostable DNA-linked RNase H may be useful to cleave RNA
      molecules with highly ordered structures in a sequence-specific manner.

PMID- 11239089
TI  - Non-ionic detergent affects the conformation of a functionally active mutant of
      Bcl-X(L).
AB  - We found that a mutant, Bcl-X(L)(F131V), which was previously reported to have
      impaired binding capacity, can bind to Bax almost as strongly as wild-type Bcl
      X(L). In the absence of detergent, the Bcl-X(L)(F131V) mutant adopts the same
      conformation as wild-type Bcl-X(L), as determined by circular dichroism
      spectroscopy and size-exclusion chromatography. However, non-ionic detergent
      induces a conformational change in the Bcl-X(L)(F131V) mutant and causes it to
      lose Bax-binding capacity. Wild-type Bcl-X(L), on the other hand, is more
      resistant to detergent-induced effects and retains its ability to bind Bax in the
      presence of detergent. Since it has been shown that the Bcl-X(L)(F131V) mutant
      has nearly the same anti-apoptotic activity as wild-type Bcl-X(L), it would be
      likely that the Bcl-X(L)(F131V) mutant can adopt the wild-type conformation,
      rather than the detergent-induced conformational state and can bind to Bax in
      vivo. Therefore, our data demonstrated that non-ionic detergent can have
      unpredicted effects on protein conformation, differential effects on wild-type
      and mutant Bcl-X(L) proteins in this case and may cause complications in the
      interpretation of in vitro binding studies.

PMID- 11239092
TI  - Consumer & family information. Panic disorder.

PMID- 11239093
TI  - Depression and satisfaction with health plans.

PMID- 11239094
TI  - Emergency assessments of domestic violence, sexual dangerousness, and elder and
      child abuse.

PMID- 11239095
TI  - Men's sexual health after midlife.

PMID- 11239096
TI  - Electroconvulsive therapy in rehabilitation: the Hong Kong experience.
AB  - Persistent psychotic symptoms can intrude on an individual's cognitive and
      psychosocial functioning and interfere with that person's active and constructive
      participation in social and vocational rehabilitation. Amelioration or
      elimination of intrusive positive and negative symptoms of psychosis is the major
      task for clinicians during the acute phase of schizophrenia. Successful treatment
      permits the patient to transition into stabilization and recovery phases, when
      psychosocial rehabilitation can take primacy (1). The introduction of clozapine
      has enlarged the proportion of individuals with schizophrenia whose psychotic
      symptoms can be controlled (2), but symptoms remain refractory in a large number
      of patients. One largely unexplored alternative for treating individuals who are
      chronically disabled is electroconvulsive therapy (ECT). Already known for its
      efficacy in treating affective disorders, its effectiveness in treating
      schizophrenia--although more limited--has been documented over more than five
      decades (3,4). ECT has been found to be particularly effective in treating first
      episode cases in which affective and catatonic symptoms are manifested and in 20
      to 50 percent of treatment-resistant cases, including those in which the patient
      was nonresponsive to clozapine (5,6,7,8). Without continuation and maintenance
      ECT, however, results are usually short-lived (4,7,9). Tang and Ungvari have used
      ECT in an attempt to increase the responsiveness to psychosocial rehabilitation
      of patients who have treatment-refractory schizophrenia. They describe their
      experiences with ECT at a facility in Hong Kong, where long-term hospitalization
      is still the norm for a sizable proportion of patients with chronic
      schizophrenia. ECT is more compatible with the biological view of schizophrenia
      that is prevalent in Asian countries; hence it has greater cultural congruence
      and acceptability among consumers and families in China than in the United
      States.

PMID- 11239097
TI  - Implementing supported employment as an evidence-based practice.
AB  - Supported employment for people with severe mental illness is an evidence-based
      practice, based on converging findings from eight randomized controlled trials
      and three quasi-experimental studies. The critical ingredients of supported
      employment have been well described, and a fidelity scale differentiates
      supported employment programs from other types of vocational services. The
      effectiveness of supported employment appears to be generalizable across a broad
      range of client characteristics and community settings. More research is needed
      on long-term outcomes and on cost-effectiveness. Access to supported employment
      programs remains a problem, despite their increasing use throughout the United
      States. The authors discuss barriers to implementation and strategies for
      overcoming them based on successful experiences in several states.

PMID- 11239098
TI  - Special section on involuntary outpatient commitment: introduction.

PMID- 11239099
TI  - A randomized controlled trial of outpatient commitment in North Carolina.
AB  - OBJECTIVE: A randomized controlled trial of outpatient commitment was conducted
      in North Carolina to provide empirical data on involuntary outpatient commitment
      and to evaluate its effectiveness in improving outcomes among persons with severe
      mental illnesses. METHODS: A total of 331 involuntarily hospitalized patients
      awaiting discharge under outpatient commitment were randomly assigned to be
      released or to undergo outpatient commitment. Each received case management
      services and outpatient treatment. Participants in both groups were monitored for
      one year. After the initial 90-day outpatient commitment order, a patient could
      receive a renewable 180-day extension. Patients in the control group were immune
      from outpatient commitment for one year. Information was obtained from self
      reports and reports of several informants as well as from outpatient treatment,
      hospital, and arrest records. RESULTS: In most bivariate analyses, outcomes for
      the outpatient commitment group and the control group did not differ
      significantly when the duration of outpatient commitment was not taken into
      account. However, patients who underwent sustained outpatient commitment and who
      received relatively intensive outpatient treatment had fewer hospital admissions
      and fewer days in the hospital, were more likely to adhere to community
      treatment, and were less likely to be violent or to be victimized. Extended
      outpatient commitment was also associated with fewer arrests of participants with
      a combined history of multiple rehospitalizations and previous arrests. The
      intervention was particularly effective among individuals with psychotic
      disorders. CONCLUSIONS: Outpatient commitment can improve treatment outcomes when
      the court order is sustained and combined with relatively intensive community
      treatment. A court order alone cannot substitute for effective treatment in
      improving outcomes.

PMID- 11239100
TI  - Assessing the New York City involuntary outpatient commitment pilot program.
AB  - OBJECTIVE: The study evaluated the effectiveness of a three-year outpatient
      commitment pilot program established in 1994 at Bellevue Hospital in New York
      City. METHODS: A total of 142 participants were randomly assigned; 78 received
      court-ordered treatment, which included enhanced services, and 64 received the
      enhanced-service package only. Between 57 and 68 percent of the subjects
      completed interviews at one, five, and 11 months after hospital discharge.
      Outcome measures included rehospitalization, arrest, quality of life,
      symptomatology, treatment noncompliance, and perceived level of coercion.
      RESULTS: On all major outcome measures, no statistically significant differences
      were found between the two groups. No subject was arrested for a violent crime.
      Eighteen percent of the court-ordered group and 16 percent of the control group
      were arrested at least once. The percentage rehospitalized during follow-up was
      about the same for both groups-51 percent and 42 percent, respectively. The
      groups did not differ significantly in the total number of days hospitalized
      during the follow-up period. Participants' perceptions of their quality of life
      and level of coercion were about the same. From the community service providers'
      perspective, patients in the two groups were similarly adherent to their required
      treatments. CONCLUSIONS: All results must be qualified by the fact that no pick
      up order procedures for noncompliant subjects in the court-ordered group were
      implemented during the study, which compromised the differences between the
      conditions for the two groups, and that persons with a history of violence were
      excluded from the program.

PMID- 11239101
TI  - Outpatient commitment: what, why, and for whom.
AB  - The authors describe studies showing the effectiveness of involuntary outpatient
      commitment in improving treatment compliance, reducing hospital readmission, and
      reducing episodes of violence among persons with severe psychiatric illnesses.
      They point out that because of its role in enhancing compliance with treatment,
      outpatient commitment can be regarded as a form of assisted treatment, such as
      assertive case management, representative payeeship, and mental health courts.
      The authors argue that such assisted treatment is necessary for persons with
      severe psychiatric illnesses who are noncompliant with their medication regimens
      because many lack awareness of their illnesses because of biologically based
      cognitive deficits. They recommend outpatient commitment for any individual with
      a severe psychiatric disorder who has impaired awareness of his or her illness
      and is at risk of becoming homeless, incarcerated, or violent or of committing
      suicide, and they provide case examples. The authors conclude by addressing eight
      of the most common objections to outpatient commitment by mental health
      professionals and civil liberties groups that oppose outpatient commitment.

PMID- 11239102
TI  - Opening pandora's box: the practical and legal dangers of involuntary outpatient
      commitment.
AB  - Policy makers have recently begun to reconsider involuntary outpatient commitment
      as a means of enhancing public safety and providing mental health services to
      people deemed to be noncompliant with treatment. The authors review the
      therapeutic claims for outpatient commitment and take the position that there is
      insufficient evidence that it is effective. They offer arguments that outpatient
      commitment may not improve public safety and may not be more effective than
      voluntary services. The authors further point out that outpatient commitment may
      undermine the delivery of voluntary services and may drive consumers away from
      the mental health system. The authors conclude that outpatient commitment
      programs are vulnerable to legal challenge because they may depart from
      established constitutional standards for involuntary treatment.

PMID- 11239103
TI  - Thinking carefully about outpatient commitment.
AB  - We are witnessing an unprecedented wave of interest in outpatient commitment. In
      part, enthusiasm for outpatient commitment stems from concerns about highly
      publicized acts of violence by persons with mental disorders, although this is
      one of the weaker justifications for new laws. Provision of involuntary
      outpatient treatment may be an important component of a system of care for
      persons with schizophrenia, bipolar disorder, and other serious mental illnesses
      for reasons entirely unrelated to the prevention of headline-grabbing acts of
      violence. The existing data, all imperfect, tend to favor the efficacy of
      outpatient commitment as a means of stabilizing patients in the community, and
      many clinicians who have been involved in the process share this view.
      Acknowledging limitations in the empirical evidence favoring outpatient
      commitment, the author reviews key issues for policy makers to address in
      considering or revising these statutes.

PMID- 11239104
TI  - Converting day treatment centers to supported employment programs in Rhode
      Island.
AB  - OBJECTIVE: The purpose of the study was to compare vocational and nonvocational
      outcomes of clients of two community mental health centers that underwent
      conversion from day treatment programs to supported employment programs with
      outcomes of clients of a center that delayed conversion until after the study was
      completed. METHODS: As part of a statewide effort in Rhode Island to convert day
      treatment programs to supported employment programs, the authors assessed 127 day
      treatment clients with severe mental illness in three community mental health
      centers. Two of the centers converted to supported employment, and one continued
      its rehabilitative day program. Participants were assessed prospectively for 30
      to 36 months, with special attention to vocational and social outcomes. RESULTS:
      Former day treatment clients in the converted centers attained higher rates of
      competitive employment than those in the comparison group (44.2 percent and 56.7
      percent versus 19.5 percent). Other employment outcomes also improved, and
      hospitalization rates and overall social functioning were unchanged. CONCLUSIONS:
      This study supports findings of previous studies suggesting that replacing
      rehabilitative day treatment programs with supported employment programs yields
      improvements in employment outcomes without adverse effects.

PMID- 11239105
TI  - Bipolar II disorder: symptoms, course, and response to treatment.
AB  - The authors provide an overview of the diagnosis, course, and treatment of
      bipolar II disorder, a distinct subtype that is often misdiagnosed as unipolar
      depression or bipolar I disorder. They discuss research suggesting that
      underdiagnosis of bipolar II disorder reflects a failure to identify subthreshold
      expression of mania (hypomania). The course of bipolar II disorder is different
      from that of bipolar I disorder or unipolar depression, with distinct differences
      in rates of recovery, clinical features, and number of episodes. The risk of
      suicide appears to be particularly elevated. High rates of comorbid disorders
      have been reported, including substance abuse or dependence, anxiety disorders,
      and personality disorders. Few definitive studies exist on which to base
      conclusions about the differential efficacy of various treatment strategies in
      bipolar II disorder and bipolar I disorder. Preliminary studies suggest that the
      newer anticonvulsants may be of benefit for patients with bipolar II disorder,
      while other data suggest that there may be a greater role for antidepressant
      medications.

PMID- 11239106
TI  - Screening the public for depression through the Internet.
AB  - OBJECTIVE: Despite increased public screening, many individuals with depression
      remain undetected or untreated. This study explored the performance of an
      Internet-based program in screening for depression. METHODS: The Centers for
      Epidemiological Studies Depression (CES-D) scale was adapted as an online
      screening test. The program advised persons whose score indicated a high
      probability of depression to seek treatment and asked them to complete a survey
      of attitudes and preferences that could be printed and taken to a health
      professional. Responses were collected anonymously for epidemiologic research.
      Demographic characteristics of participants were compared with those of the U.S.
      population and participants in previous community screenings. The costs of the
      program were calculated. RESULTS: The CES-D scale was completed 24,479 times
      during the eight-month study period. The respondents' median age category was 30
      to 45 years, and almost 30 percent were male; 58 percent (N=14,185) screened
      positive for depression, and fewer than half of those had never been treated for
      depression. The proportion of younger individuals was larger than in previous
      public screenings, but was still lower than that in the U.S. population. Our
      sample contained a lower proportion of minorities than the U.S. population (16.6
      percent versus 28.3 percent). Sunk costs totaled $9,000, and additional marginal
      costs to maintain the system totaled $3,750. CONCLUSIONS: The Internet provides a
      continuously available, inexpensive, easily maintained platform to anonymously
      screen a large number of individuals from a broad geographic area. However, older
      adults and minorities may visit screening sites less frequently than other
      populations.

PMID- 11239107
TI  - A review of the literature on the epidemiology of parasuicide in the general
      population.
AB  - OBJECTIVE: The author reviewed recent literature on the epidemiology of
      parasuicide in the general population. Major risk factors are also discussed.
      METHODS: Parasuicide was defined as suicide attempts and deliberate self-harm
      inflicted with no intent to die. Articles in English on rates of parasuicide in
      the general population from 1970 through June 2000 were identified by keyword
      searches of the PsycINFO and MEDLINE databases. Studies that provided data from a
      representative population sample and provided incidence or prevalence rates were
      included in the review. Articles focusing on subsamples such as adolescents or
      psychiatric patients were excluded. RESULTS AND CONCLUSIONS: Twenty studies were
      analyzed. Although methodological problems constitute a major limitation in
      interpretation of the results, the literature indicates that parasuicide is a
      serious public health problem. Reported annual rates of parasuicide in recent
      decades range from 2.6 to 1,100 per 100,000, and lifetime prevalence rates range
      from 720 to 5,930 per 100,000. The most important risk factors identified were
      younger age and female gender. Others included being single or divorced, being
      unemployed, having a recent change in living situation, having a mental disorder,
      and having a previous parasuicide incident.

PMID- 11239108
TI  - Outcomes of decreased length of hospital stay among geriatric patients with
      dementia.
AB  - This study examined the outcomes associated with shortening hospital stays for
      geriatric inpatients with dementia at a Veterans Administration medical center.
      Thirty-three patients who were admitted after January 1997, when the hospital
      decided to reduce patients' lengths of stay, were matched with 33 patients who
      were admitted before January 1997. Despite significant differences in lengths of
      stay, no differences were found between the groups on measures of agitation or
      overall functioning. Despite significantly shorter stays since January 1997, the
      results of our study indicate that the cognitive and emotional status of patients
      discharged since that time are equivalent to those of patients discharged after
      longer hospital stays.

PMID- 11239109
TI  - Factors associated with noncompliance with psychiatric outpatient visits.
AB  - Adherence to recommended services is essential for long-term effectiveness of
      ambulatory treatment programs, but factors associated with such adherence are not
      securely established. We evaluated attendance at 896 scheduled psychiatric clinic
      visits for 62 patients at a major psychiatric teaching hospital. Visit adherence
      was found to be significantly higher among patients in an acute stage of illness,
      those with a personality disorder, those with a post-high-school education, and
      those living alone. Adherence was also higher when visits were routinely
      scheduled, when the intervisit interval was shorter, and when the visit entailed
      psychotherapy rather than pharmacotherapy.

PMID- 11239110
TI  - Self-reported needs for care among persons who have suicidal ideation or who have
      attempted suicide.
AB  - This study examined the self-reported needs of suicidal users of mental health
      services and the extent to which needs were met. Data on 10,641 adults were
      available from the Australian National Survey of Mental Health and Wellbeing. In
      the year before the survey, 245 persons with suicidal ideation used services, 37
      of whom had attempted suicide. Suicidal persons reported a range of needs,
      especially for counseling, medication, and information. More than half of those
      with suicidal ideation and those who had attempted suicide who reported any needs
      felt that their needs had not been fully met. Suicidal persons were significantly
      more likely to perceive that they had needs.

PMID- 11239111
TI  - Schizophrenia is not contagious.

PMID- 11239112
TI  - The paradox of command hallucinations.

PMID- 11239114
TI  - Implementing family-friendly services.

PMID- 11239115
TI  - Insight and moderating variables.

PMID- 11239117
TI  - Psychiatric disorders and their management in general practice.

PMID- 11239118
TI  - Psychiatric residents as CME presenters.

PMID- 11239120
TI  - George L. Engel, M.D., 1913-1999: remembering his life and work; rediscovering
      his soul.

PMID- 11239121
TI  - Coping with grim news from genetic tests.
AB  - Clinicians need to recognize and respond to stress response syndromes that may
      occur after patients have received genetic testing for inherited susceptibility
      to serious diseases. For patients whose test results convey high risk, increased
      attention to prevention, surveillance, and early medical treatment may be
      possible, but the grim news may also lead to a formation of symptoms ranging from
      extreme denial to unwelcomed intrusive ideas and feelings. Genetic counseling
      alone may be insufficient for some people, and evaluation and psychotherapy for
      stress response syndromes may be indicated for them.

PMID- 11239122
TI  - INTERMED--a clinical instrument for biopsychosocial assessment.
AB  - Using the INTERMED, a system for classifying case complexity, the authors
      evaluated patients admitted to a general internal medicine ward on length of stay
      (LOS), number of medicines prescribed during the hospital stay, and whether they
      had received specialist medical consults. Using the patients' INTERMED scores,
      the authors divided the patients into three clusters of patients: standard
      (n=41), chronic (n=26), and complex (n=18). A comparison of the three clusters
      indicated that patients who had scored within the complex cluster were at risk of
      requiring complex care and an increased LOS. The findings suggest that the
      INTERMED detects complex patients at admission and may, therefore, be used for
      early integral case management.

PMID- 11239123
TI  - Alcoholism treatment after liver transplantation: lessons learned from a clinical
      trial that failed.
AB  - Alcoholic liver disease is the second most common indication for liver
      transplantation in the United States. The lack of alcoholism treatment studies
      led us to study motivational enhancement therapy (MET) plus naltrexone after
      transplant. The authors could not complete this study. Sixty alcoholic patients
      were to receive MET plus naltrexone or placebo for 6 months. Fifty men and 5
      women were screened. Nine died and 15 were not approached. Of 31 approached, 20
      were ineligible, 11 refused, and 5 entered but dropped out before completion.
      Barriers to posttransplant alcoholism included infirmity, intensive medical
      management, and denial for alcoholism treatment. Because 30%-50% of alcoholic
      patients drink after transplant, the authors suggest using MET alone
      pretransplant.

PMID- 11239124
TI  - Quality of life in breast cancer patients--not enough attention for long-term
      survivors?
AB  - In a study of breast cancer survivors, the authors used the European Organization
      for Research and Treatment of Cancer core questionnaire + breast module (EORTC
      QLQ-C30/+BR23) and the Functional Assessment of Cancer Therapy-Breast (FACT-B)for
      the assessment of quality of life (QoL). The main focus of this study was to look
      at the effect of time elapsed since initial treatment on the patients' QoL.
      Eighty-seven female patients (average age of 53.9 +/- 8.7 years) were included in
      the study. All women had received curative cancer therapy. The average time
      elapsed since start of initial treatment was 4.7 +/- 4.3 years. Reduced QoL,
      especially in the areas of emotional, social, and sexual functioning, was found
      not only after initial treatment (1-2 years) but also after long posttreatment
      survival (> 5 years). From these findings, needs for specific psycho-oncological
      interventions are derived. The findings imply that besides recovering from the
      acute consequences of cancer therapy, long-term survivors of breast cancer (> 5
      years after initial treatment) still may have a special need for psycho
      oncological support.

PMID- 11239125
TI  - Psychosocial effects of enhanced external counterpulsation in the angina patient:
      a second study.
AB  - Enhanced external counterpulsation (EECP) is a noninvasive technique that has
      shown promise in the treatment of ischemic coronary artery disease. Patients
      undergoing EECP were tested for alterations in psychosocial state associated with
      treatment. Overall perception of health and quality of life improved with EECP.
      There was also significant improvement in levels of depression, anxiety, and
      somatization but no change in levels of anger or hostility. On most measures,
      change was more significant for subjects who showed objective evidence of
      resolution of ischemia. Given the known predictive relationship between
      depression and mortality from cardiac disease, the improvement in depression
      scores through EECP indicates a finding of potential importance that may warrant
      further study in future research.

PMID- 11239126
TI  - Psychophysiologic assessment of posttraumatic stress disorder in breast cancer
      patients.
AB  - The authors performed psychodiagnostic, psychometric, and psychophysiologic
      evaluations on 37 patients referred by local surgeons approximately 2 years after
      tissue diagnosis of Stage I to III breast cancer. The Clinician-Administered
      Posttraumatic Stress Disorder (PTSD) Scale (CAPS) was used to classify patients
      into the following groups: "Current PTSD" (n = 5) "Past PTSD" (n = 7), and "Never
      had PTSD" (n = 25). Individualized "scripts" portraying personal life events were
      tape recorded and played back to the patients in the laboratory. Current PTSD
      patients showed significantly higher heart rate, skin conductance, and corrugator
      electromyogram responses during imagery of their personal breast cancer
      experiences than Past and Never patients. Physiologic responses were
      significantly and positively correlated with CAPS scores. These results provide
      psychophysiologic support for the proposition that a diagnosis of with a life
      threatening illness can cause PTSD.

PMID- 11239127
TI  - Why do some cancer patients with depression desire an early death and others do
      not?
AB  - Major depression is a well-documented risk factor for suicide in cancer patients
      as well as in the general population. However, there are no data explaining why
      some cancer patients suffering from major depression have suicidal ideation,
      while others do not. The authors investigated the background differences among
      cancer patients suffering from major depression with and without suicidal
      ideation by analyzing the consultation data of patients referred to the
      psychiatry division. Among the 1,721 referred patients, 220 (12.8%) were
      diagnosed with major depression, and of these 113 (51.4%) had suicidal ideation.
      Logistic regression analysis indicated that poor physical functioning and severe
      depression were significant risk factors. These preliminary findings suggest that
      the severity of major depression and physical functioning are important
      indicators of suicidal ideation among cancer patients.

PMID- 11239128
TI  - The construct validity and clinical utility of the Frank Jones story as a brief
      screening measure of cognitive dysfunction.
AB  - The use of quick and easily administered screening measures of cognitive
      functioning has become increasingly important in clinical settings. A number of
      brief screening instruments are available, but few have been thoroughly examined
      for their validity and clinical utility. The Frank Jones Story is a 2-minute
      screening procedure proposed to measure problem solving by asking patients to
      explain an absurd proposition. The authors used this screen to help them classify
      155 patients as cognitively impaired or unimpaired based on a full
      neuropsychological evaluation. Overall, the total score on the Frank Jones Story
      was a good predictor of intact functioning for patients that were unimpaired but
      was poor at predicting cognitive dysfunction. However, various subscores of the
      test reflected differing patterns of sensitivity and specificity for cognitive
      impairment. These data suggest that the Frank Jones Story might have some utility
      for initial screening for cognitive dysfunction.

PMID- 11239129
TI  - Factitious hypertension by pseudoephedrine.

PMID- 11239130
TI  - Metoclopramide-induced akathisia during the second trimester of a 37-year-old
      woman's first pregnancy.

PMID- 11239131
TI  - Consultation-liaison psychiatry drug-drug interactions update.

PMID- 11239132
TI  - Can sertraline induce parkinson's disease?

PMID- 11239133
TI  - "Paradoxical psychiatric syndrome" of the recipient after child-to-parent living
      related liver transplantation.

PMID- 11239135
TI  - Decision analysis and the evaluation of decision technologies.

PMID- 11239136
TI  - Preparation and training: the key to better patient involvement.

PMID- 11239137
TI  - Improving the quality of surgeons' treatment decisions: a comparison of clinical
      decision making with a computerised evidence based decision analytical model.
AB  - OBJECTIVES: The purpose of this study is to demonstrate to what extent an
      evidence based decision model can improve physicians' decisions and whether a
      selective use of the decision model is feasible. METHODS: Four experienced
      vascular surgeons were asked to make a treatment decision for 137 "paper patient"
      cases with asymptomatic abdominal aneurysms. Their decisions were compared with
      the optimal treatment as calculated by a computerised evidence based decision
      analytical model. RESULTS: Surgeons agreed with the model's advice based on life
      expectancy in 81% of the cases, and decided to operate in only 12% of the cases
      for which there was no agreement. Surgeons' decisions differed from the decision
      model's calculated optimal treatment, in particular, for older patients with
      aneurysms of intermediate size and with many risk factors, and for younger
      patients with small aneurysms and few risk factors. Not all these decisions,
      however, were reported to be more difficult. CONCLUSION: Use of a decision
      analytical model might lead to more appropriate decisions and a better quality of
      care. Selective use of the decision tool for difficult decisions only would be
      more efficient but is not yet feasible because reported decision difficulty is
      not strongly related to disagreement with the decision tool.

PMID- 11239138
TI  - Involvement of consumers in the development of evidence based clinical
      guidelines: practical experiences from the North of England evidence based
      guideline development programme.
AB  - BACKGROUND: Consumer involvement in clinical guidelines has long been advocated
      although there are few empirical accounts of attempts to do so. It is therefore
      not surprising that there is a lack of clarity about how and when to involve
      consumers and what to expect from them within the process of guideline
      development. METHODS: The North of England evidence based guideline development
      programme has used four different methods of consumer involvement. RESULTS: When
      individual patients were included in a guideline development group they
      contributed infrequently and had problems with the use of technical language.
      Although they contributed most in discussions of patient education, their
      contributions were not subsequently acted on. In a "one off" meeting with a group
      of patients there were again reported problems with medical terminology and the
      group were most interested in sections on patient education and self management.
      However, their understanding of the use of scientific evidence in order to
      contribute to a more cost effective health care remained unclear. In a workshop
      it was possible to explain the technical elements of guideline development to
      patients who could then engage with such a process and make relevant suggestions
      as a consequence. However, this was relatively resource intensive. A patient
      advocate within a guideline development group felt confidence to speak, was used
      to having discussions with health professionals, and was familiar with the
      medical terminology. CONCLUSIONS: Consumers should be involved in all stages of
      guideline development. While this is possible, it is not straightforward. There
      is no one right way to accomplish this and there is a clear need for further work
      on how best to achieve it.

PMID- 11239139
TI  - Development of a multidimensional labour satisfaction questionnaire: dimensions,
      validity, and internal reliability.
AB  - BACKGROUND: No published quantitative instrument exists to measure maternal
      satisfaction with the quality of different models of labour care in the UK.
      METHODS: A quantitative psychometric multidimensional maternal satisfaction
      questionnaire, the Women's Views of Birth Labour Satisfaction Questionnaire
      (WOMBLSQ), was developed using principal components analysis with varimax
      rotation of successive versions. Internal reliability and content and construct
      validity were assessed. RESULTS: Of 300 women sent the first version (WOMBLSQ1),
      120 (40%) replied; of 300 sent WOMBLSQ2, 188 (62.7%) replied; of 500 women sent
      WOMBLSQ3, 319 (63.8%) replied; and of 2400 women sent WOMBLSQ4, 1683 (70.1%)
      replied. The latter two versions consisted of 10 dimensions in addition to
      general satisfaction. These were (Cronbach's alpha): professional support in
      labour (0.91), expectations of labour (0.90), home assessment in early labour
      (0.90), holding the baby (0.87), support from husband/partner (0.83), pain relief
      in labour (0.83), pain relief immediately after labour (0.65), knowing labour
      carers (0.82), labour environment (0.80), and control in labour (0.62). There
      were moderate correlations (range 0.16-0.73) between individual dimensions and
      the general satisfaction scale (0.75). Scores on individual dimensions were
      significantly related to a range of clinical and demographic variables.
      CONCLUSION: This multidimensional labour satisfaction instrument has good
      validity and internal reliability. It could be used to assess care in labour
      across different models of maternity care, or as a prelude to in depth
      exploration of specific areas of concern. Its external reliability and
      transferability to care outside the South West region needs further evaluation,
      particularly in terms of ethnicity and social class.

PMID- 11239140
TI  - Patient satisfaction with out of hours primary medical care.
AB  - OBJECTIVES: To describe the relationship between patient satisfaction with out of
      hours care provided by deputising and practice doctors in four urban areas in
      England and characteristics of the service provided and patients, the care given,
      and health outcomes. SETTING: -Fourteen general practices in four urban areas in
      England. PARTICIPANTS: People who requested out of hours care. DESIGN: Analysis
      of data from a study of out of hours care. Patients were interviewed within 5
      days of their request for out of hours care. Data on the service provided were
      obtained from medical records and all other data were collected at interview.
      Satisfaction was measured using a valid reliable instrument. RESULTS: 2152
      patients were recruited to the study and 1466 were interviewed. Satisfaction data
      were available on 1402 patients. "Overall satisfaction" was associated with age,
      doctor type, lack of access to a car at the time of the request, and health
      outcome. The relationships between satisfaction subscales and patient
      characteristics (age, sex, ethnicity, and access to a car at the time of the
      request), service characteristics (doctor type and delay between the request and
      visit), whether a prescription was given, and health outcome were variable. If an
      expected home visit was not received, "overall satisfaction" and satisfaction
      with "communication and management", "doctor's attitude", and "initial contact
      person" were reduced. CONCLUSION: Patient satisfaction is dependent on many
      factors. Mismatch between patient expectation and the service received is related
      to decreased satisfaction. This may increase as general practitioners delegate
      more out of hours care to cooperatives and deputising services.

PMID- 11239141
TI  - Institutional resilience in healthcare systems.

PMID- 11239142
TI  - Improving the interface between primary and secondary care: a statement from the
      European Working Party on Quality in Family Practice (EQuiP).
AB  - A group from the European Working Party on Quality in Family Practice (EQuiP),
      working with over 20 European colleges of primary care, has assessed what, in
      their view, is needed to improve the quality of care at the interface between
      general practice and specialists. Experiences and ideas from a wide range of
      people were gathered through focused group discussions. From these it was clear
      that, for real improvement at the interface of care, changes are needed in the
      system of care and in the ways that doctors view their roles and their
      performance. All providers of care need to be able to see the care system from
      the patients' perspective if they are to help their patients make sense of and
      benefit from an increasingly complex system. This paper outlines the EQuiP
      recommendations on how cooperation between general practitioners and specialists
      might be improved. This includes strategic perspectives and both targets for
      improvement and methods for teaching, training and development that are all
      independent of country and health care system. The 10 targets for development
      identified by the group are: leadership, initial shared care approaches, task
      division, mutual guidelines, patient perspective, informatics, education, team
      building, quality monitoring systems, and cost effectiveness. Working towards
      these targets could provide an effective approach to improving the cooperation
      between the interfaces of care. Getting effective leadership is a necessary first
      step as implementation of such a strategy will involve significant change.
      Responsibility lies primarily with the medical profession.

PMID- 11239143
TI  - Management matters: the link between hospital organisation and quality of patient
      care.
AB  - Some hospital trusts and health authorities consistently outperform others on
      different dimensions of performance. Why? There is some evidence that "management
      matters", as well as the combined efforts of individual clinicians and teams.
      However, studies that have been conducted on the link between the organisation
      and management of services and quality of patient care can be criticised both
      theoretically and methodologically. A larger, and arguably more rigorous, body of
      work exists on the performance of firms in the private sector, often conducted
      within the disciplines of organisational behaviour or human resource management.
      Studies in these traditions have focused on the effects of decentralisation,
      participation, innovative work practices, and "complementarities" on outcome
      variables such as job satisfaction and performance. The aim of this paper is to
      identify a number of reviews and research traditions that might bring new ideas
      into future work on the determinants of hospital performance. Ideally, future
      research should be more theoretically informed and should use longitudinal rather
      than cross sectional research designs. The use of statistical methods such as
      multilevel modelling, which allow for the inclusion of variables at different
      levels of analysis, would enable estimation of the separate contribution that
      structure and process make to hospital outcomes.

PMID- 11239145
TI  - Examining evidence of reproductive isolation in sockeye salmon.

PMID- 11239144
TI  - Management of upper gastrointestinal cancers.

PMID- 11239146
TI  - X-ray pulses approaching the attosecond frontier.
AB  - Single soft-x-ray pulses of approximately 90-electron volt (eV) photon energy are
      produced by high-order harmonic generation with 7-femtosecond (fs), 770-nanometer
      (1.6 eV) laser pulses and are characterized by photoionizing krypton in the
      presence of the driver laser pulse. By detecting photoelectrons ejected
      perpendicularly to the laser polarization, broadening of the photoelectron
      spectrum due to absorption and emission of laser photons is suppressed,
      permitting the observation of a laser-induced downshift of the energy spectrum
      with sub-laser-cycle resolution in a cross correlation measurement. We measure
      isolated x-ray pulses of 1.8 (+0.7/-1.2) fs in duration, which are shorter than
      the oscillation cycle of the driving laser light (2.6 fs). Our techniques for
      generation and measurement offer sub-femtosecond resolution over a wide range of
      x-ray wavelengths, paving the way to experimental attosecond science. Tracing
      atomic processes evolving faster than the exciting light field is within reach.

PMID- 11239147
TI  - Hierarchical organization of guidance receptors: silencing of netrin attraction
      by slit through a Robo/DCC receptor complex.
AB  - Axonal growth cones that cross the nervous system midline change their
      responsiveness to midline guidance cues: They become repelled by the repellent
      Slit and simultaneously lose responsiveness to the attractant netrin. These
      mutually reinforcing changes help to expel growth cones from the midline by
      making a once-attractive environment appear repulsive. Here, we provide evidence
      that these two changes are causally linked: In the growth cones of embryonic
      Xenopus spinal axons, activation of the Slit receptor Roundabout (Robo) silences
      the attractive effect of netrin-1, but not its growth-stimulatory effect, through
      direct binding of the cytoplasmic domain of Robo to that of the netrin receptor
      DCC. Biologically, this hierarchical silencing mechanism helps to prevent a tug
      of-war between attractive and repulsive signals in the growth cone that might
      cause confusion. Molecularly, silencing is enabled by a modular and interlocking
      design of the cytoplasmic domains of these potentially antagonistic receptors
      that predetermines the outcome of their simultaneous activation.

PMID- 11239148
TI  - On atmospheric loss of oxygen ions from earth through magnetospheric processes.
AB  - In Earth's environment, the observed polar outflow rate for O(+) ions, the main
      source of oxygen above gravitational escape energy, corresponds to the loss of
      approximately 18% of the present-day atmospheric oxygen over 3 billion years.
      However, part of this apparent loss can actually be returned to the atmosphere.
      Examining loss rates of four escape routes with high-altitude spacecraft
      observations, we show that the total oxygen loss rate inferred from current
      knowledge is about one order of magnitude smaller than the polar O(+) outflow
      rate. This disagreement suggests that there may be a substantial return flux from
      the magnetosphere to the low-latitude ionosphere. Then the net oxygen loss over 3
      billion years drops to approximately 2% of the current atmospheric oxygen
      content.

PMID- 11239149
TI  - Quantum mechanical actuation of microelectromechanical systems by the Casimir
      force.
AB  - The Casimir force is the attraction between uncharged metallic surfaces as a
      result of quantum mechanical vacuum fluctuations of the electromagnetic field. We
      demonstrate the Casimir effect in microelectromechanical systems using a
      micromachined torsional device. Attraction between a polysilicon plate and a
      spherical metallic surface results in a torque that rotates the plate about two
      thin torsional rods. The dependence of the rotation angle on the separation
      between the surfaces is in agreement with calculations of the Casimir force. Our
      results show that quantum electrodynamical effects play a significant role in
      such microelectromechanical systems when the separation between components is in
      the nanometer range.

PMID- 11239150
TI  - Spherical bilayer vesicles of fullerene-based surfactants in water: a laser light
      scattering study.
AB  - The low solubility of fullerenes in aqueous solution limits their applications in
      biology. By appropriate substitution, the fullerenes can be transformed into
      stabilized anions that are water soluble and can form large aggregated
      structures. A laser light scattering study of the association behavior of the
      potassium salt of pentaphenyl fullerene (Ph5C60K) in water revealed that the
      hydrocarbon anions Ph5C60- associate into bilayers, forming stable spherical
      vesicles with an average hydrodynamic radius and a radius of gyration of about 17
      nanometers at a very low critical aggregation concentration of less than 10(-7)
      moles per liter. The average aggregation number of associated particles in these
      large spherical vesicles is about 1.2 x 10(4).

PMID- 11239151
TI  - Nanobelts of semiconducting oxides.
AB  - Ultralong beltlike (or ribbonlike) nanostructures (so-called nanobelts) were
      successfully synthesized for semiconducting oxides of zinc, tin, indium, cadmium,
      and gallium by simply evaporating the desired commercial metal oxide powders at
      high temperatures. The as-synthesized oxide nanobelts are pure, structurally
      uniform, and single crystalline, and most of them are free from defects and
      dislocations. They have a rectanglelike cross section with typical widths of 30
      to 300 nanometers, width-to-thickness ratios of 5 to 10, and lengths of up to a
      few millimeters. The beltlike morphology appears to be a distinctive and common
      structural characteristic for the family of semiconducting oxides with cations of
      different valence states and materials of distinct crystallographic structures.
      The nanobelts could be an ideal system for fully understanding dimensionally
      confined transport phenomena in functional oxides and building functional devices
      along individual nanobelts.

PMID- 11239152
TI  - High macromolecular synthesis with low metabolic cost in Antarctic sea urchin
      embryos.
AB  - Assessing the energy costs of development in extreme environments is important
      for understanding how organisms can exist at the margins of the biosphere.
      Macromolecular turnover rates of RNA and protein were measured at -1.5 degrees C
      during early development of an Antarctic sea urchin. Contrary to expectations of
      low synthesis with low metabolism at low temperatures, protein and RNA synthesis
      rates exhibited temperature compensation and were equivalent to rates in
      temperate sea urchin embryos. High protein metabolism with a low metabolic rate
      is energetically possible in this Antarctic sea urchin because the energy cost of
      protein turnover, 0.45 joules per milligram of protein, is 1/25th the values
      reported for other animals.

PMID- 11239153
TI  - A short duration of the Cretaceous-Tertiary boundary event: evidence from
      extraterrestrial helium-3.
AB  - Analyses of marine carbonates through the interval 63.9 to 65.4 million years ago
      indicate a near-constant flux of extraterrestrial helium-3, a tracer of the
      accretion rate of interplanetary dust to Earth. This observation indicates that
      the bolide associated with the Cretaceous-Tertiary (K-T) extinction event was not
      accompanied by enhanced solar system dustiness and so could not have been a
      member of a comet shower. The use of helium-3 as a constant-flux proxy of
      sedimentation rate implies deposition of the K-T boundary clay in (10 +/- 2) x
      10(3) years, precluding the possibility of a long hiatus at the boundary and
      requiring extremely rapid faunal turnover.

PMID- 11239154
TI  - Continuous mantle melt supply beneath an overlapping spreading center on the East
      Pacific Rise.
AB  - Tomographic images of upper mantle velocity structure beneath an overlapping
      spreading center (OSC) on the East Pacific Rise indicate that this ridge axis
      discontinuity is underlain by a continuous region of low P-wave velocities. The
      anomalous structure can be explained by an approximately 16-kilometer-wide region
      of high temperatures and melt fractions of a few percent by volume. Our results
      show that OSCs are not necessarily associated with a discontinuity in melt supply
      and that both OSC limbs are supplied with melt from a mantle source located
      beneath the OSC. We conclude that tectonic segmentation of the ridge by OSCs is
      not the direct result of magmatic segmentation at mantle depths.

PMID- 11239155
TI  - Hepatitis C virus IRES RNA-induced changes in the conformation of the 40s
      ribosomal subunit.
AB  - Initiation of protein synthesis in eukaryotes requires recruitment of the 40S
      ribosomal subunit to the messenger RNA (mRNA). In most cases, this depends on
      recognition of a modified nucleotide cap on the 5' end of the mRNA. However, an
      alternate pathway uses a structured RNA element in the 5' untranslated region of
      the messenger or viral RNA called an internal ribosomal entry site (IRES). Here,
      we present a cryo-electron microscopy map of the hepatitis C virus (HCV) IRES
      bound to the 40S ribosomal subunit at about 20 A resolution. IRES binding induces
      a pronounced conformational change in the 40S subunit and closes the mRNA binding
      cleft, suggesting a mechanism for IRES-mediated positioning of mRNA in the
      ribosomal decoding center.

PMID- 11239156
TI  - A proteolytic transmembrane signaling pathway and resistance to beta-lactams in
      staphylococci.
AB  - beta-Lactamase and penicillin-binding protein 2a mediate staphylococcal
      resistance to beta-lactam antibiotics, which are otherwise highly clinically
      effective. Production of these inducible proteins is regulated by a signal
      transducing integral membrane protein and a transcriptional repressor. The signal
      transducer is a fusion protein with penicillin-binding and zinc metalloprotease
      domains. The signal for protein expression is transmitted by site-specific
      proteolytic cleavage of both the transducer, which autoactivates, and the
      repressor, which is inactivated, unblocking gene transcription. Compounds that
      disrupt this regulatory pathway could restore the activity of beta-lactam
      antibiotics against drug-resistant strains of staphylococci.

PMID- 11239157
TI  - Recovery of infectious Ebola virus from complementary DNA: RNA editing of the GP
      gene and viral cytotoxicity.
AB  - To study the mechanisms underlying the high pathogenicity of Ebola virus, we have
      established a system that allows the recovery of infectious virus from cloned
      cDNA and thus permits genetic manipulation. We created a mutant in which the
      editing site of the gene encoding envelope glycoprotein (GP) was eliminated. This
      mutant no longer expressed the nonstructural glycoprotein sGP. Synthesis of GP
      increased, but most of it accumulated in the endoplasmic reticulum as immature
      precursor. The mutant was significantly more cytotoxic than wild-type virus,
      indicating that cytotoxicity caused by GP is down-regulated by the virus through
      transcriptional RNA editing and expression of sGP.

PMID- 11239158
TI  - Genetic correlates of musical pitch recognition in humans.
AB  - We used a twin study to investigate the genetic and environmental contributions
      to differences in musical pitch perception abilities in humans. We administered a
      Distorted Tunes Test (DTT), which requires subjects to judge whether simple
      popular melodies contain notes with incorrect pitch, to 136 monozygotic twin
      pairs and 148 dizygotic twin pairs. The correlation of DTT scores between twins
      was estimated at 0.67 for monozygotic pairs and 0.44 for dizygotic pairs. Genetic
      model-fitting techniques supported an additive genetic model, with heritability
      estimated at 0.71 to 0.80, depending on how subjects were categorized, and with
      no effect of shared environment. DTT scores were only weakly correlated with
      measures of peripheral hearing. This suggests that variation in musical pitch
      recognition is primarily due to highly heritable differences in auditory
      functions not tested by conventional audiologic methods.

PMID- 11239159
TI  - Presynaptic kainate receptor mediation of frequency facilitation at hippocampal
      mossy fiber synapses.
AB  - Inhibition of transmitter release by presynaptic receptors is widespread in the
      central nervous system and is typically mediated via metabotropic receptors. In
      contrast, very little is known about facilitatory receptors, and synaptic
      activation of a facilitatory autoreceptor has not been established. Here we show
      that activation of presynaptic kainate receptors can facilitate transmitter
      release from hippocampal mossy fiber synapses. Synaptic activation of these
      presumed ionotropic kainate receptors is very fast (<10 ms) and lasts for
      seconds. Thus, these presynaptic kainate receptors contribute to the short-term
      plasticity characteristics of mossy fiber synapses, which were previously thought
      to be an intrinsic property of the synapse.

PMID- 11239160
TI  - Binding of DCC by netrin-1 to mediate axon guidance independent of adenosine A2B
      receptor activation.
AB  - Netrins stimulate and orient axon growth through a mechanism requiring receptors
      of the DCC family. It has been unclear, however, whether DCC proteins are
      involved directly in signaling or are mere accessory proteins in a receptor
      complex. Further, although netrins bind cells expressing DCC, direct binding to
      DCC has not been demonstrated. Here we show that netrin-1 binds DCC and that the
      DCC cytoplasmic domain fused to a heterologous receptor ectodomain can mediate
      guidance through a mechanism involving derepression of cytoplasmic domain
      multimerization. Activation of the adenosine A2B receptor, proposed to contribute
      to netrin effects on axons, is not required for rat commissural axon outgrowth or
      Xenopus spinal axon attraction to netrin-1. Thus, DCC plays a central role in
      netrin signaling of axon growth and guidance independent of A2B receptor
      activation.

PMID- 11239161
TI  - Filopodial calcium transients promote substrate-dependent growth cone turning.
AB  - Filopodia that extend from neuronal growth cones sample the environment for
      extracellular guidance cues, but the signals they transmit to growth cones are
      unknown. Filopodia were observed generating localized transient elevations of
      intracellular calcium ([Ca2+]i) that propagate back to the growth cone and
      stimulate global Ca2+ elevations. The frequency of filopodial Ca2+ transients was
      substrate-dependent and may be due in part to influx of Ca2+ through channels
      activated by integrin receptors. These transients slowed neurite outgrowth by
      reducing filopodial motility and promoted turning when stimulated differentially
      within filopodia on one side of the growth cone. These rapid signals appear to
      serve both as autonomous regulators of filopodial movement and as frequency-coded
      signals integrated within the growth cone and could be a common signaling process
      for many motile cells.

PMID- 11239162
TI  - Requirement for the SLP-76 adaptor GADS in T cell development.
AB  - GADS is an adaptor protein implicated in CD3 signaling because of its ability to
      link SLP-76 to LAT. A GADS-deficient mouse was generated by gene targeting, and
      the function of GADS in T cell development and activation was examined. GADS- CD4
      CD8- thymocytes exhibited a severe block in proliferation but still
      differentiated into mature T cells. GADS- thymocytes failed to respond to CD3
      cross-linking in vivo and were impaired in positive and negative selection.
      Immunoprecipitation experiments revealed that the association between SLP-76 and
      LAT was uncoupled in GADS- thymocytes. These observations indicate that GADS is a
      critical adaptor for CD3 signaling.

PMID- 11239165
TI  - Peripheral blood stem cells for allogeneic transplantation: a review.
AB  - Peripheral blood stem cells (PBSCs) have become increasingly popular for use in
      hematopoietic stem cell transplantation. PBSCs are readily collected by
      continuous-flow apheresis from patients and healthy donors after the
      administration of s.c. recombinant colony-stimulating factors with only minimal
      morbidity and discomfort. Although the precise identification of PBSCs remains
      elusive, they can be phenotypically identified as a subset of all circulating
      CD34(+) cells. There are important phenotypic and biologic distinctions between
      PBSCs and bone marrow (BM)-derived progenitor cells. PBSCs express more lineage
      specific antigens but are less metabolically active than their BM-derived
      counterparts. The use of PBSCs for allogeneic transplantation has been compared
      to BM in several randomized trials and cohort studies. The use of PBSCs in
      leukemia, myeloma, non-Hodgkin's lymphoma, and myelodysplasia has resulted in
      shorter times to neutrophil and platelet engraftment at the expense of increased
      rates of chronic graft-versus-host disease. The increase in graft-versus-host
      disease is mainly due to a log-fold increase in donor T cells transferred with
      the graft. Relapse rates after transplantation may be lower after PBSC
      transplantation but a convincing survival advantage has not been demonstrated
      overall. It is possible that a stronger graft-versus-tumor effect may exist with
      PBSCs when compared with BM although the mechanisms leading to this effect are
      not clear.

PMID- 11239164
TI  - Autocrine/paracrine mechanisms in human hematopoiesis.
AB  - Autocrine/paracrine regulatory mechanisms are believed to play a role in the
      pathophysiology of several hematologic malignancies. Evidence is accumulating
      that various growth factors, cytokines, and chemokines are expressed and secreted
      by normal early and differentiated hematopoietic cells and thus could also
      regulate normal hematopoiesis in an autocrine/paracrine manner. In this review we
      summarize recent advances in identification and understanding of the role of
      autocrine/paracrine axes in the growth of both malignant and normal human
      hematopoietic cells. Better understanding of intercellular crosstalk operating in
      normal and pathological states and the mechanisms regulating synthesis of these
      endogenously produced factors (potential targets for various pharmacological
      approaches) may allow us to improve antileukemia treatments, undertake more
      efficient ex vivo stem cell expansion, and develop other therapeutic strategies.

PMID- 11239166
TI  - "Rainbow" reporters for multispectral marking and lineage analysis of
      hematopoietic stem cells.
AB  - Hematologic diseases potentially benefiting from gene-based therapies involving
      hematopoietic stem cells (HSCs) include hereditary hemoglobinopathies,
      immunodeficiency syndromes, and congenital bleeding disorders such as hemophilia
      A, as well as acquired diseases like AIDS. Successful treatment of these blood
      diseases with gene-modified HSCs requires high efficiency gene delivery to the
      target cell population and persistence of transgene expression following
      differentiation. We review flow cytometric procedures that permit simultaneous,
      noninvasive measurements of transgene expression and phenotypic discrimination of
      hematopoietic cell subsets. Central to this approach has been the recent
      development of a spectrum of blue, cyan, and yellowish-green fluorescent
      reporters based on the jellyfish Aequorea victoria green fluorescent protein and
      the discovery of a red fluorescent protein in DISCOSOMA: coral. This methodology
      should facilitate the optimization of oncoretroviral and lentiviral vectorology
      and HSC transduction protocols for the ultimate purpose of HSC-directed gene
      therapy.

PMID- 11239167
TI  - The role of C/EBP(epsilon) in the terminal stages of granulocyte differentiation.
AB  - As a consequence of its characterization using both in vitro and knockout mouse
      models, the myeloid-specific transcription factor, CCAAT/enhancer binding protein
      (C/EBP)epsilon, has been identified as a critical regulator of terminal
      granulopoiesis and one of the causative mutations in the human disease,
      neutrophil-specific granule deficiency. C/EBPs are a family of transcription
      factors sharing numerous structural and functional features and to date include
      C/EBPalpha, -beta, -gamma, -delta, -epsilon, and -zeta. C/EBPalpha was the first
      family member isolated and characterized, its essential role in hepatocyte and
      adipocyte differentiation demonstrated in knockout mouse models. Subsequent
      analysis of the hematopoietic elements in fetal mouse liver revealed its critical
      role in myelopoiesis. Understanding the role of C/EBPepsilon in terminal
      granulopoiesis in the context of other known transcription factors is ongoing
      with analysis of deficient and conditionally expressing cell lines and knockout
      models. Mouse models with targeted gene disruptions have contributed greatly to
      our understanding of the transcriptional regulation of granulopoiesis. Further
      manipulation of these models and other conditional expression systems have
      bypassed some of the limitations of knockout models and helped delineate the
      interactions of different transcription factors in affecting granulocyte
      development. Phenotypic expression of the loss of C/EBPepsilon in mice is
      extreme, resembling absolute neutropenia with systemic infection with P.
      aeruginosa. Future work will need to explore the regulation of C/EBPepsilon
      expression, its functional interactions with other transcriptional regulators
      such as PU.1, and its role in monocyte differentiation and function in the mouse.

PMID- 11239168
TI  - Expression of adhesion molecules on CD34(+) cells in peripheral blood of non
      hodgkin's lymphoma patients mobilized with different growth factors.
AB  - Adhesion molecules on CD34(+) cells were implicated in the process of peripheral
      blood stem cell (PBSC) mobilization and homing. We studied the mobilization of
      CD34(+)Thy1(+) cells, CD34(+) very late-acting antigen (VLA)4(+) cells, and
      CD34(+)L-selectin(+) cells in non-Hodgkin's lymphoma patients mobilized with
      cyclophosphamide plus G-CSF, GM-CSF, or GM-CSF followed by G-CSF. The mean
      percentage of CD34(+) cells in the bone marrow (BM) expressing Thy1 was 23.6% +/-
      11% and 17.8% +/- 8% in the PB before mobilization, and was markedly decreased to
      4.5% +/- 3.3% in the apheresis collections. Similarly, the mean percentage of
      CD34(+) cells expressing L-selectin was 35.8% +/- 4.3% in the BM, 21.6% +/- 4.1%
      in the PB before mobilization and was markedly decreased to 9.1% +/- 2.5% in the
      apheresis collections. Patients in the three arms of the study had a similar
      pattern of CD34(+)Thy1(+) and CD34(+)L-selectin(+) cell mobilization. Also, a
      similar pattern of coexpression of CD34(+)Thy1(+) and CD34(+)L-selectin(+) cells
      was observed when the patients were regrouped as "good mobilizers" (> or =2 x
      10(6) CD34(+)CD45(dim) cells/kg, in four collections) and "poor mobilizers" (<0.4
      x 10(6) CD34(+)CD45(dim) cells/kg, in two collections). The mean percentage of
      CD34(+) cells expressing VLA-4 in the BM and PB was relatively high (73.4% +/-
      12% and 65.4% +/- 6.6%, respectively) and dropped considerably in the PBSC
      collections to 43.5% +/- 7.1% with a similar pattern observed for patients in
      arms A, B, and C. However, when the patients were regrouped as "good mobilizers"
      and "poor mobilizers," a higher percentage of CD34(+) cells expressing VLA-4 was
      observed in the PBSC of the pooled "good mobilizers" (50.5% +/- 9% versus 36.3%
      +/- 6.4%; p = 0.01). We conclude that release of CD34(+) cells to the PB involves
      a general downregulation of Thy1, L-selectin and VLA-4 on CD34(+) cells,
      irrespective of the growth factor used for mobilization. However, good mobilizers
      had a relatively higher percentage of CD34(+) cells expressing the VLA-4 antigen.

PMID- 11239169
TI  - Successful allogeneic bone marrow transplantation (BMT) by injection of bone
      marrow cells via portal vein: stromal cells as BMT-facilitating cells.
AB  - We examined the importance of the coadministration of bone marrow (BM) stromal
      cells with BM cells via the portal vein. A significant increase in the number of
      day-14 colony-forming unit-spleen (CFU-S) was observed in the recipient mice
      injected with hemopoietic stem cells (HSCs) along with donor BM stromal cells
      obtained after three to four weeks of culture. Histological examination revealed
      that hematopoietic colonies composed of both donor hemopoietic cells and stromal
      cells coexist in the liver of these mice. However, when donor HSCs plus BM
      stromal cells were administered i.v., neither the stimulatory effects on CFU-S
      formation nor the hemopoietic colonies in the recipient liver were observed.
      These findings suggest that the interaction of HSCs with stromal cells in the
      liver is the first crucial step for successful engraftment of allogeneic HSCs. It
      is likely that donor stromal cells and HSCs trapped in the liver migrate into the
      recipient BM and spleen, where they form CFU-BM and CFU-S, respectively.

PMID- 11239171
TI  - The molecular perspective: targeted toxins.

PMID- 11239170
TI  - Comparison of double and triple high-dose chemotherapy with autologous blood stem
      cell transplantation in patients with metastatic breast cancer.
AB  - In patients with metastatic breast cancer (MBC), early dose intensification with
      multiple cycles of peripheral blood stem cell-supported high-dose chemotherapy
      (HDCT) seems superior to a late dose-intensification strategy. We compared the
      progression-free survival (PFS) and overall survival (OS) of 20 patients treated
      with a double (D)-HDCT regimen to 20 patients who received a triple (T)-HDCT,
      matched by age, estrogen receptor (ER) status, adjuvant chemotherapy, initial
      disease-free interval, predominant metastatic site, and number of metastatic
      sites. At a median follow-up of 41.5 months (range, 14-88 months) an intent-to
      treat analysis showed no difference in PFS (p = 0.72) and OS (p = 0.93) between
      the matched patients. For all 76 patients treated within the D- or T-HDCT trial,
      median PFS and OS was 13 months (range, 2-78 months) and 24.5 months (range, 7-78
      months), respectively. In multivariate analysis independent predictors of shorter
      OS included negative ER (relative risk [RR] = 3.0 [95% confidence interval (CI)
      1.5-5.9]; p = 0.002), more than two metastatic sites (RR = 2.4 [95% CI 1.0-5.7];
      p = 0.049) and failure to achieve complete remission/no evidence of disease
      (CR/NED) after HDCT (RR = 4.5 [95% CI 2.0-10.1]; p < 0.0001). These data show
      that early dose intensification with T-HDCT is not superior to a D-HDCT regimen
      in patients with MBC. ER-negative tumors, more than two metastatic sites and no
      CR/NED after HDCT, are associated with inferior outcome.

PMID- 11239172
TI  - Visual cloning 2000.

PMID- 11239173
TI  - Stroke: 30 years of progress: 1977-1981.

PMID- 11239174
TI  - Treatment of unruptured cerebral aneurysms in California.
AB  - BACKGROUND AND PURPOSE: The impact of endovascular therapy on treatment outcomes
      of unruptured cerebral aneurysms has not been studied in a defined geographic
      area. METHODS: All primary diagnoses of unruptured aneurysms were retrieved from
      a statewide database of hospital discharges in California from January 1990
      through December 1998. Admissions for initial treatment and all follow-up care
      were combined to reflect the entire course of therapy. An adverse outcome was
      defined as an in-hospital death or discharge to nursing home or rehabilitation
      hospital at any point during the treatment course. Multivariable analyses were
      performed with generalized estimating equations with adjustment for age, sex,
      ethnicity, source of admission, year of treatment, hospital volume, and
      clustering of observations at institutions. RESULTS: A total of 2069 patients
      were treated for unruptured aneurysms. Adverse outcomes were more frequent in the
      1699 patients treated with surgery (25%) than in those treated with endovascular
      therapy (10%; P:<0.001). The difference persisted after multivariable adjustment
      (surgery versus endovascular therapy: odds ratio for adverse outcomes, 3.1; 95%
      CI, 2.5 to 4.0; P:<0.001). Adverse outcomes declined from 1991 to 1998 in
      patients treated with endovascular therapy (P:<0.005) but not for surgery. In
      hospital deaths occurred in 3.5% of surgical cases and 0.5% of endovascular cases
      (P:=0.003), and the difference remained significant after adjustment (odds ratio,
      6.3; 95% CI, 3.5 to 11.4; P:<0.001). Total length of stay and hospital charges
      were greater in surgical cases (both P:<0.001). Results were similar in a
      confirmatory analysis focusing on treatment differences between institutions.
      Institutional treatment volume was also associated with outcome but did not
      account for the differences between surgery and endovascular therapy.
      CONCLUSIONS: In California, endovascular therapy of unruptured aneurysms is
      associated with less risk of adverse outcomes and in-hospital death, lower
      hospital charges, and shorter hospital stays compared with surgery. Differences
      between therapies became more distinct through the years. Uncontrolled
      differences in prognosis of patients receiving endovascular therapy and surgery
      cannot be ruled out in this study of discharge abstracts.

PMID- 11239175
TI  - Hormonal factors and risk of aneurysmal subarachnoid hemorrhage: an international
      population-based, case-control study.
AB  - BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) is more common in women
      than in men, but the role of hormonal factors in its etiology remains uncertain.
      The aim of this study was to examine the relationship between hormonal factors
      and risk of SAH in women. METHODS: This was a prospective, multicenter,
      population-based, case-control study performed in 4 major urban centers in
      Australia and New Zealand. Two hundred sixty-eight female cases of first-ever
      aneurysmal SAH occurred during 1995-1998. Controls were 286 frequency-matched
      women from the general population of each center. Outcome measures included risk
      of SAH associated with use of oral contraceptive pills (OCPs), hormone
      replacement therapy (HRT), and various endogenous hormonal factors including
      menstrual patterns, parity, age at birth of first child, and breast-feeding
      practices. RESULTS: Cases and controls did not differ with regard to menstrual
      and reproductive history except in age at birth of first child, where older age
      was associated with reduced risk of SAH (odds ratio [OR], 0.63; 95% CI, 0.43,
      0.91). Relative to never use of HRT, the adjusted OR for ever use of HRT was 0.64
      (95% CI, 0.41, 0.98), which did not alter significantly after further adjustment
      for possible confounding factors. Borderline evidence of an inverse association
      was detected for past use of HRT (adjusted OR, 0.59; 95% CI, 0.30, 1.13) and
      current use of HRT (adjusted OR, 0.67; 95% CI, 0.40, 1.13), but there was no
      evidence of an association for use of OCPs (adjusted OR, 0.97; 95% CI, 0.58,
      1.60). CONCLUSIONS: The risks of SAH are lower in women whose first pregnancy is
      at an older age and women who have ever used HRT but not OCPs. The findings
      suggest an independent etiologic role for hormonal factors in the pathogenesis of
      aneurysmal SAH and provide support for a protective role for HRT on risk of SAH
      in postmenopausal women.

PMID- 11239176
TI  - Is there a temporal pattern in the occurrence of subarachnoid hemorrhage in the
      southern hemisphere? Pooled data from 3 large, population-based incidence studies
      in Australasia, 1981 to 1997.
AB  - BACKGROUND AND PURPOSE: Publications on the temporal pattern of the occurrence of
      subarachnoid hemorrhage (SAH) have produced conflicting results. Variations
      between studies may relate to the relatively small numbers of SAH cases analyzed,
      including those in meta-analyses. METHODS: We identified all cases of SAH from 3
      well-designed population-based studies in Australia (Adelaide, Hobart, and Perth)
      and New Zealand (Auckland) during 3 periods between 1981 and 1997. The diagnosis
      of SAH was confirmed with CT, cerebral angiography, cerebrospinal fluid analysis,
      or autopsy in all cases. Information on the time of occurrence of each event was
      obtained. Risk ratios (RRs) and 95% CIs were calculated using Poisson regression,
      with age, sex, smoking status, and history of hypertension entered in the model
      as covariates. RESULTS: A total of 783 cases of SAH were registered. Age- and sex
      adjusted RRs of SAH occurrence were highest in the period between 6 AM and 12
      MIDNIGHT (RR 3.2, 95% CI 2.4-4.3) and in winter and spring (RR 1.3, 95% CI 1.1
      1.5; RR 1.3, 95% CI 1.1-1.5; respectively). No particular pattern of SAH
      occurrence was observed according to the day of the week. Restriction of the
      analyses to proved aneurysmal SAH did not substantially change the point
      estimates. CONCLUSIONS: Circadian and circaseptan (weekly) fluctuations of SAH
      occurrence in the southern hemisphere are similar to those in the northern
      hemisphere, but the occurrence of SAH in Australasia exhibits clear seasonal
      (winter and spring) peaks.

PMID- 11239177
TI  - Effects of aging on cerebral vasospasm after subarachnoid hemorrhage in rabbits.
AB  - BACKGROUND AND PURPOSE: The effects of aging on cerebral vasospasm after
      subarachnoid hemorrhage (SAH) remain to be elucidated. The aim of this study was
      to clarify age-related differences of vasospasm and of papaverine reactivity in
      the responses of basilar arteries after SAH in rabbits. METHODS: Rabbits
      receiving a single injection of arterial blood into the cisterna magna were
      divided into 3 groups: young (2 to 3 months old), adult (6 to 9 months old), and
      old (20 to 40 months old). Vertebrobasilar angiograms were obtained before SAH
      and 1, 2, 4, and 7 days after SAH. Papaverine was administrated selectively via
      the vertebral artery on day 2, and serial angiography was performed for up to 2
      hours. Vessel structures were assessed with light microscopy on days 1, 2, 4, and
      7 after SAH and at 10, 30, and 60 minutes after papaverine infusion. RESULTS:
      Mortality from SAH in old rabbits was 40%, whereas that of young and adult
      rabbits was 0%. Angiograms revealed that SAH induced maximal constriction of the
      basilar arteries on day 2 in all age groups, and the constrictions were
      significantly increased with age at all time points investigated. The degree of
      dilatation of spastic basilar arteries after intra-arterial papaverine
      administration significantly decreased with age. Duration of the efficacy of
      papaverine became significantly shorter with age. Vessel diameter returned to the
      preinfusion value approximately 120, 60, and 30 minutes after infusion in young,
      adult, and old rabbits, respectively. Light microscopy in old rabbits showed
      luminal narrowing and corrugation of the internal elastic lamina not only in the
      basilar arteries but also in small arteries and intraparenchymal arterioles.
      CONCLUSIONS: This study suggests that aging increases the degree of vasospasm in
      rabbits. The impaired reactivity to papaverine with aging might imply the early
      transition of the aged vessel to the papaverine-resistant chronic stage.

PMID- 11239178
TI  - Hemodynamic consequences of cerebral vasospasm on perforating arteries: a phantom
      model study.
AB  - BACKGROUND AND PURPOSE: Hemodynamics of cerebral vasospasm after subarachnoid
      hemorrhage remain unclear, and the discrepancy between ultrasonographic or
      angiographic evidence of arterial narrowing and neurological ischemic deficit is
      still debated. Most blood flow studies have been involved with large arteries,
      and thus, very little is known regarding the hemodynamic behavior of small
      perforating vessels. Patients with symptomatic vasospasm, however, often present
      with neurological signs suggesting involvement of deep-sited areas of the brain
      supplied by perforating arteries. METHODS: A pulsatile pump was set to provide an
      outflow of 350 mL/min through a 10-mm-diameter C-flex tube at a perfusion
      pressure of 130/80 mm Hg. The perfusion fluid used was prepared to approximate
      blood viscosity. Perforating arteries were simulated by a 1-mm tube connected to
      the parent tube at a 90 degrees angle. Cylindrical stenotic devices of decreasing
      diameters were then introduced into the parent tube at the level of the aperture
      of the secondary tube and 1.5 diameters upstream of it. Velocity profiles both
      proximal and distal to the stenosis in the parent tube were obtained with a newly
      developed ultrasonographic flowmeter that allows for high spatial resolution.
      RESULTS: Increasing stenosis resulted in decreased outflow in the main tube,
      although it was significant only with severe stenosis. Whenever the simulated
      stenosis was placed upstream of the secondary tube, flow reduction was associated
      with a progressive change in the velocity profile, which gradually changed from
      laminar conditions to a jet stream limited to the center of the lumen. Further
      diameter reduction was responsible for the occurrence of flow separation with
      retrograde flow velocities in the periphery of the lumen. In the secondary tube,
      flow reduction was much more pronounced and began at a lesser degree of stenosis.
      Increasing fluid viscosity and decreasing perfusion pressure enhanced flow
      separation and prominently affected the outflow in the secondary tube.
      Conversely, whenever the simulated stenosis involved the branching area of the
      secondary tube, there was a slightly progressive decrease in the relative flow in
      the main tube as the stenosis became tighter. When the stenosis equaled the
      diameter of the secondary tube, the relative contribution of the secondary tube
      increased markedly at the expense of the main tube outflow. CONCLUSIONS: The
      present results show that local cerebral vasospasm induces changes in
      postvasospastic velocity profile affecting the shear rate and may eventually lead
      to flow separation. This phenomenon may, in turn, result in a venturi-like effect
      over the aperture of perforating arteries branching out of the postvasospastic
      portion of the affected parent artery. These alterations of cerebral hemodynamics
      may account for at least part of the vasospasm symptomatology, especially in the
      vertebrobasilar system, where vasospasm is commonly focal rather than diffuse.
      Furthermore, these changes proved to be affected significantly by manipulations
      of pressure and viscosity, supporting the use of hyperdynamic therapy in the
      management of cerebral vasospasm.

PMID- 11239179
TI  - Intracisternal increase of superoxide anion production in a canine subarachnoid
      hemorrhage model.
AB  - BACKGROUND AND PURPOSE: Reactive oxygen species (ROS) are thought to be primary
      in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH).
      However, as direct evidence of ROS has not yet been demonstrated in cerebral
      vasospasm, we sought to substantiate superoxide anion (.O(2)(-)) generation in
      the subarachnoid space after SAH using a modification of Karnovsky's
      manganese/diaminobenzidine (Mn(2+)/DAB) technique. METHODS: SAH or sham operation
      was induced according to a 2-hemorrhage model in a total of 24 beagle dogs. On
      day 2 or 7 after SAH or sham operation, dogs were intrathecally infused with
      buffer containing Mn(2+) and DAB, and the brain stem was prepared for light and
      electron microscopy. Possible colocalization of ferrous (Fe(2+)) or ferric
      (Fe(3+)) iron ions with.O(2)(-) was also examined with the use of Turnbull blue
      or Berlin blue staining, respectively. RESULTS: Light microscopy revealed
      amorphous, amber deposits within the subarachnoid hematoma, the periarterial
      space, and the tunica adventitia of the basilar artery on days 2 and 7 after
      SAH.O(2)(-) deposits were eliminated by addition of superoxide dismutase or
      exclusion of either Mn(2+) or DAB from the perfusate, confirming the specificity
      of the reaction. These deposits were colocalized with blue reaction deposits
      indicating Fe(2+) and Fe(3+). Within the subarachnoid space,.O(2)(-) indicating
      electron-dense fine granules were preferentially located around degenerated
      erythrocytes and, secondarily, infiltrating macrophages and neutrophils.
      CONCLUSIONS: We show direct evidence for enhanced production of.O(2)(-) and
      Fe(2+)/Fe(3+) iron ions in the subarachnoid space after SAH, lending further
      support to the pathogenic role of ROS in cerebral vasospasm after SAH.

PMID- 11239180
TI  - Correlations between clinical findings and magnetization transfer imaging metrics
      of tissue damage in individuals with cerebral autosomal dominant arteriopathy
      with subcortical infarcts and leukoencephalopathy.
AB  - BACKGROUND AND PURPOSE: We obtained magnetization transfer imaging (MTI) scans
      from individuals with cerebral autosomal-dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy (CADASIL) (1) to investigate the presence,
      extent, and nature of pathology in white and gray matter outside proton density
      (PD)-visible lesions; (2) to quantify the degree of tissue damage occurring in
      lesions seen on PD-weighted scans; and (3) to correlate MTI-derived measures of
      disease burden with age, physical disability, and cognitive performance. METHODS:
      Dual-echo, T1-weighted, and MTI scans of the brain were obtained from 33
      individuals with CADASIL and 12 control subjects. Magnetization transfer ratio
      (MTR) values from PD-visible lesions, normal-appearing white matter (NAWM), and
      normal-appearing gray matter (NAGM) were measured. Histograms of MTR from the
      whole brain and normal-appearing brain tissue were also produced. RESULTS: All
      MTR values from NAWM and NAGM regions studied were significantly lower for
      individuals with CADASIL than for control subjects, with the exception of those
      obtained from the NAWM of the infratentorial structures and the NAGM of the
      occipital cortex. The average MTR from PD lesions in individuals with CADASIL was
      significantly lower than that from all the NAWM regions. Average MTR and peak
      location from whole-brain and normal-appearing brain tissue histograms were
      significantly lower for individuals with CADASIL than for control subjects. MTR
      values from NAWM were strongly correlated with the extent of macroscopic lesions
      and their average MTR. Apart from NAGM, average MTR from all other tissues
      studied significantly decreased with increasing age, physical disability, and
      cognitive impairment. CONCLUSIONS: PD lesions of individuals with CADASIL have
      variable degrees of tissue damage. Brain tissue outside PD abnormalities is also
      damaged. This study suggests that the extent and the severity of the brain tissue
      damage are critical factors in determining clinical status in CADASIL.

PMID- 11239181
TI  - Transtentorial herniation after unilateral infarction of the anterior cerebral
      artery.
AB  - BACKGROUND: Fatal cerebral herniation is a common complication of large
      ("malignant") middle cerebral artery infarcts but has not been reported in
      unilateral anterior cerebral artery (ACA) infarction. CASE DESCRIPTION: We report
      a 47-year-old woman who developed an acute left hemiparesis during an attack of
      migraine. Cranial CT (CCT) was normal but demonstrated narrow external
      cerebrospinal fluid compartments. Transcranial Doppler sonography was compatible
      with occlusion of the right ACA. Systemic thrombolytic therapy with tissue
      plasminogen activator was initiated 105 minutes after symptom onset. Follow-up
      CCT 24 hours after treatment revealed subtotal ACA infarction with hemorrhagic
      conversion. Two days later, the patient suddenly deteriorated with clinical signs
      of cerebral herniation, as confirmed by CCT. An extended right hemicraniectomy
      was immediately performed. Within 6 months, the patient regained her ability to
      walk but remained moderately disabled. CONCLUSIONS: This is the first reported
      case of unilateral ACA infarct leading to almost fatal cerebral herniation.
      Narrow external cerebrospinal fluid compartments in combination with early
      reperfusion, hemorrhagic transformation, and additional dysfunction of the blood
      brain barrier promoted by tissue plasminogen activator and migraine may have
      contributed to this unusual course.

PMID- 11239182
TI  - Regional access to acute ischemic stroke intervention.
AB  - BACKGROUND AND PURPOSE: Benefit-risk ratios from recombinant tissue plasminogen
      activator (rtPA) therapy for acute ischemic stroke demonstrate lack of efficacy
      if intravenous administration is commenced beyond 3 hours of symptom onset. We
      undertook to enhance therapeutic effectiveness by ensuring equitable access to
      rtPA for patients affected by acute ischemic stroke within a 20 000 km(2)
      population referral base served by a tertiary facility. METHODS: Representatives
      of all provider groups involved in emergency medical services developed a
      Regional Acute Stroke Protocol (RASP), a coordinated regional system response by
      dispatch personnel, paramedics, physicians, community service providers,
      emergency and inpatient staff in community hospitals, and the tertiary facility
      acute stroke team. RESULTS: As of July 26, 1999, all ambulance services in
      Southeastern Ontario began bypassing the closest hospital to deliver patients
      meeting the criteria for the RASP to the Kingston General Hospital. At 12 months,
      approximately 403 ischemic strokes have occurred in the region, the RASP has been
      activated 191 times, and 42 patients have received rtPA. CONCLUSIONS: We conclude
      that (1) acute stroke patients in Southeastern Ontario have improved access to
      interventions for stroke care; (2) geography of the region is not a barrier to
      access to interventions for patients with acute stroke; and (3) acute ischemic
      stroke patients treated with rtPA account for 5% of all acute strokes and 10% of
      all ischemic strokes in this region.

PMID- 11239183
TI  - Retrospective assessment of initial stroke severity: comparison of the NIH Stroke
      Scale and the Canadian Neurological Scale.
AB  - BACKGROUND AND PURPOSE: The NIH Stroke Scale (NIHSS) and the Canadian
      Neurological Scale (CNS) have been reported to be useful for the retrospective
      assessment of initial stroke severity. However, unlike the CNS, the NIHSS
      requires detailed neurological assessments that may not be reflected in all
      patient records, potentially limiting its applicability. We assessed the
      reliability of the retrospective algorithms and the proportions of missing items
      for the NIHSS and CNS in stroke patients admitted to an academic medical center
      (AMC) and 2 community hospitals. METHODS: Randomly selected records of patients
      with ischemic stroke admitted to an AMC (n=20) and community hospitals with (CH1,
      n=19) and without (CH2, n=20) acute neurological consultative services were
      reviewed. NIHSS and CNS scores were assigned independently by 2 neurologists
      using published algorithms. Interrater reliability of the scores was determined
      with the intraclass correlation coefficient, and the numbers of missing items
      were tabulated. RESULTS: The intraclass correlation coefficient for NIHSS and
      CNS, respectively, were 0.93 (95% CI, 0.82 to 1.00) and 0.97 (95% CI, 0.90 to
      1.00) for the AMC, 0.89 (95% CI, 0.75 to 1.00) and 0.88 (95%, 0.73 to 1.00) for
      the CH1, and 0.48 (95% CI, 0.26 to 0.70) and 0.78 (95% CI, 0.60 to 0.96) for the
      CH2. More NIHSS items were missing at the CH2 (62%) versus the AMC (27%) and the
      CH1 (23%, P:=0.0001). In comparison, 33%, 0%, and 8% of CNS items were missing
      from records from CH2, AMC, and CH1, respectively (P:=0.0001). CONCLUSIONS: The
      levels of interrater agreement were almost perfect for retrospectively assigned
      NIHSS and CNS scores for patients initially evaluated by a neurologist at both an
      AMC and a CH. Levels of agreement for the CNS were substantial at a CH2, but
      interrater agreement for the NIHSS was only moderate in this setting. The
      proportions of missing items are higher for the NIHSS than the CNS in each
      setting, particularly limiting its application in the hospital without acute
      neurological consultative services.

PMID- 11239184
TI  - Clinical deterioration following improvement in the NINDS rt-PA Stroke Trial.
AB  - BACKGROUND AND PURPOSE: Little is known in regard to cerebral arterial
      reocclusion after successful thrombolysis. In the absence of arteriographic
      information, the National Institute of Neurological Disorders and Stroke (NINDS)
      rt-PA Stroke Trial investigators prospectively identified clinical deterioration
      following improvement (DFI) as a possible surrogate marker of cerebral arterial
      reocclusion after rt-PA-induced recanalization. Also, we identified any
      significant clinical deterioration (CD) even if not preceded by improvement. This
      observational analysis was designed to determine the incidence of DFI and CD in
      each treatment group, to identify baseline or posttreatment variables predictive
      of DFI or CD, and to determine any relationship between DFI, CD, and clinical
      outcome. METHODS: DFI was defined as any 2-point deterioration on the NIH Stroke
      Scale after an initial 2-point improvement after treatment. CD was defined as any
      4-point worsening after treatment compared with baseline. All data were collected
      prospectively by investigators blinded to treatment allocation. A noncontrast
      brain CT was mandated when a 2-point deterioration occurred. All cases were
      validated by a central review committee. RESULTS: DFI was identified in 81 of the
      624 patients (13%); 44 were treated with rt-PA and 37 were treated with placebo
      (P:=0.48). DFI occurred more often in patients with a higher baseline NIH Stroke
      Scale score. CD within the first 24 hours occurred in 98 patients (16% of all
      patients); 43 were given rt-PA and 55 were given placebo (P:=0.19). Baseline
      variables associated with CD included a less frequent use of prestroke aspirin
      and a higher incidence of early CT changes of edema or mass effect or dense
      middle cerebral artery sign. Patients with CD had higher rates of increased serum
      glucose and fibrin degradation products, and they also had higher rates of
      symptomatic intracranial hemorrhage and death. Patients who experienced either
      DFI or CD were less likely to have a 3-month favorable outcome. CONCLUSIONS: We
      found no association between DFI, CD, and rt-PA treatment, and no clinical
      evidence to suggest reocclusion. Deterioration was strongly associated with
      stroke severity and poor outcome and was less frequent in patients whose stroke
      occurred while they were on aspirin.

PMID- 11239185
TI  - Have randomized controlled trials of neuroprotective drugs been underpowered? An
      illustration of three statistical principles.
AB  - BACKGROUND AND PURPOSE: The results of phase III trials of neuroprotective drugs
      for acute ischemic stroke have been disappointing. We examine the question of
      whether these trials may have been underpowered. METHODS: Computer simulations
      were based on the binomial distribution. RESULTS: We illustrate that even small
      overestimates of the efficacy of an intervention can lead to a serious reduction
      in statistical power, that the use of data from phase II studies tends to lead to
      such overestimation, and that a minimum clinically important difference derived
      with cost-effectiveness modeling techniques is considerably smaller than might be
      suggested by intuition. CONCLUSIONS: We recommend placing more emphasis on
      minimum clinically important differences when planning stroke trials, with these
      differences being derived from an assessment of the public health impact obtained
      in conjunction with the use of epidemiological and cost-effectiveness models.
      Even small benefits, when averaged over a sufficiently large number of cases,
      will, in total, accrue to a large positive impact on the public health.

PMID- 11239186
TI  - Tolerability and pharmacokinetics of the nitrone NXY-059 in patients with acute
      stroke.
AB  - BACKGROUND AND PURPOSE: Increased free radical formation contributes to the
      damage caused to the brain by acute ischemia. NXY-059 is a nitrone-based free
      radical trapping agent in development for acute stroke. NXY-059 has
      neuroprotective efficacy when given 5 hours after onset of transient focal
      ischemia in the rat. METHODS: This was a randomized, double-blind, placebo
      controlled, parallel group, multicenter study that evaluated the safety and
      tolerability of 2 NXY-059 dosing regimens compared with placebo within 24 hours
      of acute stroke. NXY-059 was administered as either 250 mg over 1 hour followed
      by 85 mg/h for 71 hours or 500 mg over 1 hour followed by 170 mg/h for 71 hours;
      plasma concentrations were monitored. Neurological and functional outcomes were
      recorded up to 30 days. RESULTS: One hundred fifty patients were recruited, of
      whom 147 received study treatments and completed assessments (50 placebo, 48
      lower-dose NXY-059, 49 higher-dose NXY-059). Mean (+/-SD) age was 68 (+/-10)
      years, and baseline National Institutes of Health Stroke Scale score was 7.9 (+/
      6.2). Serious adverse events occurred in 16%, 23%, and 16% of patients,
      respectively, with deaths in 0%, 10%, and 4%, largely following the proportions
      with primary intracerebral hemorrhage (6%, 16%, and 8%). Hyperglycemia, headache,
      and fever were common but not related to treatment. The mean unbound steady state
      NXY-059 plasma concentrations were 25 and 45 micromol/L, respectively. Population
      pharmacokinetic analysis estimated clearance to be 4.6 L/h. CONCLUSIONS: NXY-059
      was well tolerated in patients with an acute stroke. The testing of higher doses
      in future trials may be justified.

PMID- 11239187
TI  - Two simple questions to assess outcome after stroke: a European study.
AB  - BACKGROUND AND PURPOSE: The "2 simple questions" were designed as an efficient
      way of measuring outcome after stroke. We assessed the sensitivity and
      specificity of this tool, adapted for use in 8 European centers, and used it to
      compare outcomes across centers. METHODS: Data were taken from the Biomed II
      prospective study of stroke care and outcomes. Three-month poststroke data from 8
      European centers were analyzed. Sensitivity and specificity were assessed by
      comparing responses to the 2 simple questions with Barthel Index and modified
      Rankin scale scores. Adjusting for case mix, logistic regression was used to
      compare patients in each center with "good" outcome (not dependent and fully
      recovered) at 3 months. RESULTS: Data for 793 patients were analyzed. For the
      total sample, the dependency question had a sensitivity of 88% and a specificity
      of 77%; the recovery question had a sensitivity of 78% and a specificity of 90%.
      Dependency data from Riga had much lower sensitivity. There was variation in good
      outcome between centers (P:=0.0015). Compared with the reference center (Kaunas),
      patients in Dijon, Florence, and Menorca were more likely to have good outcome,
      after adjusting for case mix. CONCLUSIONS: Dependency and recovery questions
      showed generally high sensitivity and specificity. There were significant
      differences across centers in outcome, but reasons for these are unclear. Such
      differences raise particular questions about how patients interpreted and
      answered the simple questions and the extent to which expectations of recovery
      and perceived needs for assistance vary cross-culturally.

PMID- 11239188
TI  - A quality-of-life instrument for young hemorrhagic stroke patients.
AB  - BACKGROUND AND PURPOSE: Hemorrhagic stroke has a high initial mortality rate.
      While survivors often recover motor function, many experience significant changes
      in their quality of life (QOL). Available outcome measures assess neurological
      impairment, disability, or handicap, yet often inadequately characterize the full
      impact of a stroke on patients' lives. In this study, we develop and validate a
      QOL instrument specific for young patients with hemorrhagic strokes. METHODS:
      Methodological guidelines for instrument development were initially established.
      Based on the content of 40 open-ended patient interviews, a 54-item instrument
      (HSQuale) was developed. The reliability (test-retest and internal consistency)
      and validity (content and construct) of HSQuale were assessed in another 71
      patients (18 to 49 years of age, 63% women, 77% white), at 1 year after their
      hemorrhagic stroke. Comparisons were made between HSQuale and other commonly used
      outcome measures. RESULTS: HSQuale demonstrated reproducibility (test-retest
      kappa, 0.40 to 0.96) and internal consistency (Cronbach alpha >/=0.80 for 5 of 7
      domains). HSQuale scores had broad frequency distributions (</=33% of subjects
      scored in any single score decile), avoided ceiling effects found for other
      outcome measures (Barthel Index and Short Form-36), and discriminated among
      clinically distinct subject groups (eg, intracerebral versus subarachnoid
      hemorrhage patients). CONCLUSIONS: HSQuale is a reliable and valid QOL
      instrument. Compared with other outcome measures, it assesses a broader range of
      deficits and is better able to discriminate among subgroups of hemorrhagic stroke
      survivors.

PMID- 11239189
TI  - Mortality at 12 and 24 months after stroke may be associated with depressive
      symptoms at 1 month.
AB  - BACKGROUND AND PURPOSE: Previous studies have reported mood symptoms after stroke
      to be a risk factor for later mortality. The purpose of the study was to examine
      whether mood symptoms at 1 month after stroke may be a risk factor for mortality
      at 12 and 24 months. METHODS: As a cohort within a randomized controlled trial,
      448 hospital patients were seen at 1 month after stroke and were randomized into
      a trial of psychological therapy. Follow-up was at 12 and 24 months. Mood
      symptoms were assessed by the Present State Examination and the General Health
      Questionnaire (GHQ)-28. Measures of disability before and after stroke and of
      cognitive impairment after stroke were also taken at 1 month. Mortality was
      determined at 12 and 24 months after stroke. RESULTS: In logistic regression
      analyses, mortality at 12 months was associated unifactorally with scoring on the
      GHQ-D subscale (odds ratio [OR] 2.4, 95% CI 1.3 to 4.5) and scoring in the
      highest quartile of the GHQ (OR 3.1, 95% CI 1.1 to 8.8). In multiple logistic
      regression analyses, only GHQ-D remained a significant predictor after
      controlling for other known predictors. At 24 months, scoring on GHQ-D (OR 2.4,
      95% CI 1.4 to 4.1) and in the highest GHQ quartile (OR 2.2, 95% CI 1.0 to 4.8)
      was significantly associated with mortality in unifactoral analyses. Scoring on
      the GHQ-D remained a predictor of mortality after controlling for other
      variables. Psychiatric disorder, such as major depression (according to
      International Classification of Diseases, 10th Revision), was not statistically
      significantly associated with increased mortality at 12 or 24 months.
      CONCLUSIONS: Mood symptoms on a self-reported rating scale were associated with
      12- and 24-month mortality after stroke, after adjustment for factors associated
      with stroke severity. The result is in keeping with other evidence that
      depressive symptoms are a risk factor for death from vascular disease.

PMID- 11239190
TI  - Acute and long-term increase in fracture risk after hospitalization for stroke.
AB  - BACKGROUND AND PURPOSE: The aims of this study were to determine the magnitude of
      the increase in fracture risk after hospitalization for stroke, and in particular
      to determine the time course of this risk. METHODS: The records of the Swedish
      register of patients admitted during 1987-1996 were examined to identify all
      patients who were admitted to the hospital for stroke. Patients were followed for
      subsequent hospitalizations for hip and all fractures combined. We analyzed 16.3
      million hospitalizations, from which 273 288 individuals with stroke were
      identified. A Poisson model was used to determine the absolute risk of subsequent
      fractures and the risk compared with that of the general population. RESULTS:
      After hospitalization for stroke, there was a >7-fold increase in fracture risk,
      including that for hip fracture within the first year after hospitalization for
      stroke. Thereafter, fracture risk declined toward, but did not attain, the
      baseline risk except in men and women aged >/=80 years. CONCLUSIONS: The high
      incidence of new fractures within the first year of hospitalization for stroke
      suggests that such patients should be preferentially targeted for treatment. It
      is possible that short courses of treatment at the time of stroke would provide
      important therapeutic dividends.

PMID- 11239191
TI  - Acupuncture and transcutaneous nerve stimulation in stroke rehabilitation: a
      randomized, controlled trial.
AB  - BACKGROUND AND PURPOSE: In small trials with control groups that receive no
      intervention, acupuncture has been reported to improve functional outcome after
      stroke. We studied effects of acupuncture and transcutaneous electrical nerve
      stimulation on functional outcome and quality of life after stroke versus a
      control group that received subliminal electrostimulation. METHODS: In a
      multicenter randomized controlled trial involving 7 university and district
      hospitals in Sweden, 150 patients with moderate or severe functional impairment
      were included. At days 5 to 10 after acute stroke, patients were randomized to 1
      of 3 intervention groups: (a) acupuncture, including electroacupuncture; (b)
      sensory stimulation with high-intensity, low-frequency transcutaneous electrical
      nerve stimulation that induces muscle contractions; and (c) low-intensity
      (subliminal) high-frequency electrostimulation (control group). A total of 20
      treatment sessions were performed over a 10-week period. Outcome variables
      included motor function, activities of daily living function, walking ability,
      social activities, and life satisfaction at 3-month and 1-year follow-up.
      RESULTS: At baseline, patients in each group were closely similar in all
      important prognostic variables. At 3-month and 1-year follow-ups, no clinically
      important or statistically significant differences were observed between groups
      for any of the outcome variables. The 3 treatment modalities were all conducted
      without major adverse effects. CONCLUSIONS: When compared with a control group
      that received subliminal electrostimulation, treatment during the subacute phase
      of stroke with acupuncture or transcutaneous electrical nerve stimulation with
      muscle contractions had no beneficial effects on functional outcome or life
      satisfaction.

PMID- 11239192
TI  - Mild hyperhomocyst(e)inemia: a possible risk factor for cervical artery
      dissection.
AB  - BACKGROUND AND PURPOSE: The pathogenesis of cervical artery dissection (CAD)
      remains unknown in most cases. Hyperhomocyst(e)inemia [hyperH(e)], an independent
      risk factor for cerebrovascular disease, induces damage in endothelial cells in
      animal cell culture. Consecutive patients with CAD and age-matched control
      subjects have been studied by serum levels of homocyst(e)ine and the genotype of
      5,10-methylenetetrahydrofolate reductase (MTHFR). METHODS: Twenty-six patients
      with CAD, admitted to our Stroke Unit (15 men and 11 women; 16 vertebral
      arteries, 10 internal carotid arteries), were compared with age-matched control
      subjects. All patients underwent duplex ultrasound, MR angiography, and/or
      conventional angiography. RESULTS: Mean plasma homocyst(e)ine level was 17.88
      micromol/L (range 5.95 to 40.0 micromol/L) for patients with CAD and 6.0+/-0.99
      micromol/L for controls (P:<0.001). The genetic analysis for the thermolabile
      form of MTHFR in CAD patients showed heterozygosity in 54% and homozygosity in
      27%; comparable figures for controls were 40% (P:=0.4) and 10% (P:=0.1),
      respectively. CONCLUSIONS: Mild hyperH(e) might represent a risk factor for
      cervical artery dissection. The MTHFR mutation is not significantly associated
      with CAD. An interaction between different genetic and environmental factors
      probably takes place in the cascade of pathogenetic events leading to arterial
      wall damage.

PMID- 11239193
TI  - 111In platelet scintigraphy for the noninvasive detection of carotid plaque
      thrombosis.
AB  - BACKGROUND AND PURPOSE: Thrombosis on atherosclerotic lesions in the large
      extracranial arteries is the main cause of embolization in the distal cerebral
      circulation and thus is involved in the pathogenesis of ischemic stroke. The
      assessment of biological characteristics of lesions that are predictive of
      thrombotic complications might help in stratification of the risk for stroke but
      is currently imperfect. METHODS: We compared the performance of (111)In-platelet
      scintigraphy with blood pool subtraction, ultrasound-based tissue texture
      analyses, and transcranial Doppler techniques in their ability to predict the
      occurrence of superficial thrombosis or the presence of a lipid pool in carotid
      artery plaque specimens removed at the time of carotid endarterectomy in 22
      patients with unilateral carotid artery stenosis of >70%. RESULTS: Positivity at
      (111)In-platelet scintigraphy was present in 8 patients and correctly identified
      the presence of thrombosis superimposed on a complicated plaque. Neither tissue
      texture analysis nor emboli detection by transcranial Doppler, performed in 12
      patients, significantly identified plaque thrombosis. None of the techniques used
      were able to detect the presence of a significant lipid pool inside the plaque.
      CONCLUSIONS: Indium-platelet scintigraphy is an accurate noninvasive diagnostic
      tool to detect thrombotic complications in carotid plaques. Prospective studies
      should assess its ultimate value in risk stratification, possibly to guide the
      decision of whether to perform endarterectomy in selected patient categories.

PMID- 11239194
TI  - Sustained bilateral hemodynamic benefit of contralateral carotid endarterectomy
      in patients with symptomatic internal carotid artery occlusion.
AB  - BACKGROUND AND PURPOSE: We sought to investigate whether in patients with a
      symptomatic internal carotid artery (ICA) occlusion, endarterectomy of a severe
      stenosis of the contralateral carotid artery can establish long-term cerebral
      hemodynamic improvement. METHODS: Nineteen patients were studied on average 1
      month before and 6 months after contralateral carotid endarterectomy (CEA).
      Volume flow in the main extracranial and intracranial arteries was measured with
      MR angiography. Collateral flow via the circle of Willis and the ophthalmic
      arteries was studied with MR angiography and transcranial Doppler sonography,
      respectively. Cerebral metabolism and CO(2) vasoreactivity were investigated with
      MR spectroscopy and transcranial Doppler sonography, respectively. Twelve
      nonoperated patients with a symptomatic ICA occlusion and contralateral ICA
      stenosis, who were matched for age and sex, served as control patients. RESULTS:
      In patients who underwent surgery, flow in the operated ICA increased
      significantly (P:<0.05) and flow in the basilar artery decreased significantly
      (P:<0.01) after CEA. On the occlusion side, mean flow in the middle cerebral
      artery increased significantly from 71 to 85 mL/min (P:<0.05) after CEA. The
      prevalence of collateral flow via the anterior communicating artery to the
      occlusion side increased significantly (47% before and 84% after CEA; P:<0.05),
      while the prevalence of reversed ophthalmic artery flow on the operation side
      decreased significantly (42% before and 5% after CEA; P:<0.05). In the hemisphere
      on the side of the ICA occlusion, lactate was no longer detected after CEA in 80%
      of operated patients, whereas it was no longer detected over time in 14% of
      nonoperated patients (P:<0.05). CO(2) reactivity increased significantly in
      operated patients in both hemispheres (P:<0.01). CONCLUSIONS: Contralateral CEA
      in patients with a symptomatic ICA occlusion induces cerebral hemodynamic
      improvement not only on the side of surgery but also on the side of the ICA
      occlusion.

PMID- 11239195
TI  - A common variant of endothelial nitric oxide synthase (Glu298Asp) is an
      independent risk factor for carotid atherosclerosis.
AB  - BACKGROUND AND PURPOSE: Endothelium-derived NO is formed from L-arginine by
      endothelial NO synthase (eNOS) encoded by the NOS 3 gene on chromosome 7. Because
      several studies have indicated that NO plays a key role in the development of the
      atherosclerotic process, we investigated whether common variants in the eNOS gene
      are associated with an increased risk of plaque on carotid arteries. METHODS: We
      studied 375 subjects attending the hypertension center of our institution to be
      screened for arterial hypertension. The examined subjects were classified
      according to the presence of carotid plaques (intima-media thickness >/=1.5 mm),
      and 2 intronic (CA and 27-bp repeats) polymorphisms and 1 exonic (Glu298Asp)
      polymorphism of the eNOS gene were explored. RESULTS: Only the Glu298Asp
      polymorphism of eNOS was associated with the presence of carotid plaques
      (P:<0.05). In particular, there was an excess of homozygotes for the Asp298
      variant among subjects with carotid plaques, whereas the number of subjects who
      had the Glu298 allele in exon 7 of the eNOS gene was equally distributed in both
      study groups. Interestingly, the risk of having carotid plaques was increased
      approximately 3 times in subjects who were homozygotic for the Asp298 variant
      compared with subjects who were homozygotic for the Glu298 variant and was
      independent of the other common risk factors (age, blood pressure, and smoking).
      CONCLUSIONS: Homozygosity for Asp298, a common variant of the eNOS gene, is an
      independent risk factor for carotid atherosclerosis in this study population.

PMID- 11239196
TI  - Overexpression of copper-zinc superoxide dismutase attenuates acute activation of
      activator protein-1 after transient focal cerebral ischemia in mice.
AB  - BACKGROUND AND PURPOSE: Reactive oxygen species (ROS) have been implicated in
      reperfusion injury after focal cerebral ischemia (FCI). ROS are known to regulate
      the activity of transcription factors such as activator protein-1 (AP-1), which
      is a dimer consisting of members of the Jun and Fos families. We investigated the
      role of ROS in AP-1 activity after FCI using transgenic mice that overexpressed
      copper-zinc superoxide dismutase (SOD1) and that had reduced infarction volume
      after FCI. METHODS: The SOD1 transgenic mice and their wild-type littermates were
      subjected to middle cerebral artery occlusion and reperfusion by intraluminal
      suture blockade. After 60 minutes of middle cerebral artery occlusion, mice were
      allowed to recover for 1, 2, and 4 hours before euthanasia. Protein expression of
      c-Jun and c-Fos was examined by immunohistochemistry and Western blotting. AP-1
      DNA-protein binding activity was assessed by electrophoretic mobility shift
      assays. RESULTS: In wild-type mice, immunohistochemistry demonstrated acute c-Jun
      and c-Fos activation in ischemic cortex and its outer boundary. Expression of
      both was reduced in SOD1 transgenic mice. Western blotting confirmed that SOD1
      overexpression was associated with reduced c-Jun and c-Fos protein levels in
      ischemic brain. Electrophoretic mobility shift assays revealed that the ischemia
      enhanced DNA binding activity observed in wild-type mice was reduced in SOD1
      transgenic mice. Supershift assays indicated that c-Jun participated in the bound
      AP-1 complex. CONCLUSIONS: SOD1 overexpression prevents early activation of AP-1
      after transient FCI in mice. This may block the expression of downstream target
      genes that are injurious, thereby reducing the infarction volume after transient
      FCI in mice.

PMID- 11239197
TI  - Comparison of TNK with wild-type tissue plasminogen activator in a rabbit embolic
      stroke model.
AB  - BACKGROUND AND PURPOSE: Tissue plasminogen activator (tPA) is an effective
      treatment for stroke, but its utility is limited by fear of cerebral hemorrhage.
      Tenecteplase (TNK), a genetically modified form of wild-type tPA, exhibits a
      longer biological half-life and greater fibrin specificity, features that could
      lead to fewer cerebral hemorrhages than wild-type tPA in stroke patients.
      METHODS: We injected radiolabeled blood clots into the cerebral circulation of
      New Zealand White rabbits. One hour later, we administered tPA (n=57), 0.6 mg/kg
      TNK (n=43), 1.5 mg/kg TNK (n=27), or vehicle control (n=37). A blinded observer
      examined the brains for macroscopic hemorrhage using a semiquantitative score. We
      estimated thrombolysis by assessing the amount of radiolabel remaining in the
      cerebral vessels postmortem. RESULTS: Both wild-type tPA and TNK caused
      thrombolysis in most subjects. Hemorrhage was detected in 26% (6/23) of the
      control group, 66% (27/41) of the wild-type tPA group, 55% (16/29) in the 0.6
      mg/kg TNK group, and 53% (9/17) in the 1.5-mg/kg TNK group (P:<0.05, chi(2)
      test). The tPA group was statistically significantly different from the control
      group, but the TNK and tPA groups did not differ from each other. Neither TNK nor
      tPA affected the size of the hemorrhages. CONCLUSIONS: TNK shows comparable rates
      of recanalization compared with wild-type tPA in a model of embolic stroke. While
      tPA increases hemorrhage rate, the hemorrhage associated with TNK treatment is
      not statistically different compared with controls or the tPA group. These
      findings suggest that TNK shows promise as an alternative thrombolytic treatment
      for stroke, but we could not demonstrate improved safety compared with wild-type
      tPA.

PMID- 11239198
TI  - Acute-phase proteins before cerebral ischemia in stroke-prone rats:
      identification by proteomics.
AB  - BACKGROUND AND PURPOSE: A high degree of proteinuria has been reported in stroke
      prone spontaneously hypertensive rats (SHRSP). We studied the effect of salt
      loading on the detailed protein pattern of serum and urine in 3 rat strains:
      Wistar-Kyoto, spontaneously hypertensive rats, and SHRSP, an inbred animal model
      for a complex form of cerebrovascular disorder resembling the human disease.
      METHODS: Rats were given a permissive diet and received 1% NaCl in drinking
      water. The protein pattern in body fluids was assessed over time by 2-dimensional
      electrophoretic analysis. Brain alterations were monitored by MRI and histology.
      RESULTS: Several proteins were excreted in urine after weeks of treatment and in
      advance of stroke: transferrin, hemopexin, albumin, alpha(2)-HS-glycoprotein,
      kallikrein-binding protein, alpha(1)-antitrypsin, Gc-globulin, and transthyretin.
      Markers of an inflammatory response, including very high levels of thiostatin,
      were detected in the serum of SHRSP at least 4 weeks before a stroke occurred.
      CONCLUSIONS: In SHRSP subjected to salt loading, an atypical inflammatory
      condition and widespread alterations of vascular permeability developed before
      the appearance of anomalous features in the brain detected by MRI. Urinary
      concentrations of each of the excreted serum proteins correlated positively with
      time before stroke occurred.

PMID- 11239199
TI  - Mechanisms that produce nitric oxide-mediated relaxation of cerebral arteries
      during atherosclerosis.
AB  - BACKGROUND AND PURPOSE: The first goal of the present study was to examine the
      hypothesis that relaxation of cerebral arteries to nitric oxide in primates is
      dependent on activation of soluble guanylate cyclase (sGC). The second goal was
      to determine whether the role of sGC in mediating responses to nitric oxide is
      altered in atherosclerosis. METHODS: Basilar arteries from normal and
      atherosclerotic monkeys were studied in vitro. After precontraction with
      prostaglandin F(2alpha) (0.1 to 1 micromol/L), concentration-response curves to
      authentic nitric oxide (1 nmol/L to 1 micromol/L), sodium nitroprusside (10
      nmol/L to 10 micromol/L; a nitric oxide donor), and papaverine (10 nmol/L to 10
      micromol/L; a non-nitric oxide, non-sGC-dependent stimulus) were generated in the
      presence and absence of 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 1 and
      10 micromol/L; an inhibitor of sGC). The effect of ODQ on basal tone of basilar
      arteries from normal and atherosclerotic monkeys was also examined. RESULTS:
      Nitric oxide, sodium nitroprusside, and papaverine produced relaxation that was
      similar (P:>0.05) in normal and atherosclerotic monkeys. ODQ produced marked
      inhibition (P:<0.05) of vasorelaxation in response to nitric oxide and
      nitroprusside but not papaverine. For example, relaxation of the basilar artery
      in response to nitric oxide (0.1 micromol/L) was inhibited by approximately 85%
      and 73% by ODQ (1 micromol/L) in normal and atherosclerotic monkeys,
      respectively. ODQ produced contraction of the basilar arteries, and the increase
      in tension to ODQ was greater in normal (2.7+/-0.3 g; mean+/-SE) than in
      atherosclerotic monkeys (1.4+/-0.4 g; P:<0.05). In contrast, contraction to
      prostaglandin F(2alpha) was similar in the basilar artery from normal and
      atherosclerotic monkeys. CONCLUSIONS: These findings suggest that (1) relaxation
      of cerebral arteries in primates in response to nitric oxide is normally
      dependent, in large part, on activation of sGC and (2) the influence of sGC (via
      reduced production and/or activity of basal nitric oxide) on cerebral vascular
      tone is reduced in atherosclerosis.

PMID- 11239200
TI  - Cardioprotection in pigs by exogenous norepinephrine but not by cerebral ischemia
      induced release of endogenous norepinephrine.
AB  - BACKGROUND AND PURPOSE: Endogenous norepinephrine release induced by cerebral
      ischemia may lead to small areas of necrosis in normal hearts. Conversely,
      norepinephrine may be one of the mediators that limit myocardial infarct size by
      ischemic preconditioning. Because brief ischemia in kidneys or skeletal muscle
      limits infarct size produced by coronary artery occlusion, we investigated
      whether cardiac norepinephrine release during transient cerebral ischemia also
      elicits remote myocardial preconditioning. METHODS: Forty-one crossbred pigs of
      either sex were assigned to 1 of 7 experimental groups, of which in 6 groups
      myocardial infarct size was determined after a 60-minute coronary occlusion and
      120 minutes of reperfusion. One group served as control (no pretreatment), while
      the other groups were pretreated with either cerebral ischemia or an
      intracoronary infusion of norepinephrine. RESULTS: In 10 anesthetized control
      pigs, infarct size was 84+/-3% (mean+/-SEM) of the area at risk after a 60-minute
      coronary occlusion and 120 minutes of reperfusion. Intracoronary infusion of 0.03
      nmol/kg. min(-)(1) norepinephrine for 10 minutes before coronary occlusion did
      not affect infarct size (80+/-3%; n=6), whereas infusion of 0.12 nmol/kg. min(
      )(1) limited infarct size (65+/-2%; n=7; P:<0.05). Neither 10-minute (n=5) nor 30
      minute (n=6) cerebral ischemia produced by elevation of intracranial pressure
      before coronary occlusion affected infarct size (83+/-4% and 82+/-3%,
      respectively). Myocardial interstitial norepinephrine levels tripled during
      cerebral ischemia and during low-dose norepinephrine but increased 10-fold during
      high-dose norepinephrine. Norepinephrine levels increased progressively up to 500
      fold in the area at risk during the 60-minute coronary occlusion, independent of
      the pretreatment, while norepinephrine levels remained unchanged in adjacent
      nonischemic myocardium and arterial plasma. CONCLUSIONS: Cerebral ischemia
      preceding a coronary occlusion did not modify infarct size, which is likely
      related to the modest increase in myocardial norepinephrine levels during
      cerebral ischemia. The infarct size limitation by high-dose exogenous
      norepinephrine is not associated with blunting of the ischemia-induced increase
      in myocardial interstitial norepinephrine levels.

PMID- 11239201
TI  - Methamphetamine potentiates ischemia/reperfusion insults after transient middle
      cerebral artery ligation.
AB  - BACKGROUND AND PURPOSE: Previous studies have indicated that both methamphetamine
      (MA) and ischemia/reperfusion injuries involve reactive oxygen species formation
      and activation of apoptotic mechanism. That MA could have a synergistic or
      additive effect with stroke-induced brain damage is possible. The purpose of the
      present study was to investigate whether administration of MA in vivo would
      potentiate ischemic brain injury. METHODS: Adult CD-1 mice were pretreated with
      MA or saline. Each animal later was anesthetized with chloral hydrate and placed
      in a stereotaxic frame. A subset of animals received intracerebral administration
      of glial cell line-derived neurotrophic factor (GDNF). The right middle cerebral
      artery and bilateral carotids were transiently occluded for 45 minutes. Regional
      cerebral blood flow was measured by laser Doppler. Animals were sacrificed for
      triphenyltetrazolium chloride staining and p53 mRNA Northern blot assay after 24
      hours of reperfusion. Cortical and striatal GDNF levels were assayed by ELISA.
      RESULTS: We found that pretreatment with MA increased ischemia-induced cerebral
      infarction. Ischemia or MA alone enhanced p53 mRNA expression. Moreover, MA
      potentiated expression of p53 mRNA in the ischemic mouse brain. MA pretreatment
      decreased GDNF levels in ischemic striatum. Intracerebral administration of GDNF
      before ischemia reduced MA-facilitated infarction. CONCLUSIONS: Our data indicate
      that MA exacerbates ischemic insults in brain, perhaps through the inhibition of
      GDNF-mediated pathways and suggest that MA may antagonize endogenous
      neuroprotective pathways as part of its mechanism of action.

PMID- 11239202
TI  - Anticonvulsant lamotrigine administered on reperfusion fails to improve
      experimental stroke outcomes.
AB  - BACKGROUND AND PURPOSE: Recent results suggest that selective inhibitors of
      presynaptic neuronal ion channels can diminish glutamate release during cerebral
      ischemia and modulate excitotoxic cell death. The aim of the present study was to
      evaluate lamotrigine (LTG), an antiepileptic that inhibits presynaptic sodium and
      voltage-sensitive calcium channels, as a potential stroke resuscitation agent in
      the rat. Three dosages of LTG were examined for effect on infarction volume and
      sensorimotor behavioral recovery after middle cerebral artery (MCA) occlusion.
      METHODS: Halothane-anesthetized male Wistar rats were subjected to 2 hours of MCA
      occlusion by the intraluminal occlusion technique. Physiological variables were
      controlled, and ipsilateral cortical perfusion was monitored by laser Doppler
      flowmetry throughout ischemia. At onset of reperfusion, rats received intravenous
      LTG 5, 10, or 20 mg/kg or PBS (n=9 to 11 per group) during 15 minutes. Behavioral
      assessment was completed at 3 and 7 days after stroke, and the brain was
      harvested for histology (triphenyltetrazolium chloride staining). RESULTS: Values
      are mean+/-SE. Cortical infarction volumes were unchanged in LTG-treated animals:
      14+/-6% of contralateral cortex at 5 mg/kg LTG, 17+/-7% at 10 mg/kg, and 30+/-6%
      at 20 mg/kg, versus saline-treated cohorts (12+/-3%; P:=0.19; n=9). Caudate
      putamen infarction injury was also unchanged (37+/-11% of contralateral caudate
      putamen at 5 mg/kg LTG, 44+/-8% at 10 mg/kg, and 65+/-9% at 20 mg/kg versus
      saline (38+/-11%; P:=0.18). Total infarction was not different among groups
      (P:=0.15). Consistent with histology, behavioral outcomes were unimproved by
      treatment. CONCLUSIONS: Histological damage and behavioral recovery at 7 days
      after MCA occlusion was not altered by LTG treatment over the dosage range used
      in the present study.

PMID- 11239203
TI  - Electrophysiological properties of CA1 neurons protected by postischemic
      hypothermia in gerbils.
AB  - BACKGROUND AND PURPOSE: Recent studies show that prolonged (eg, 24-hour)
      postischemic hypothermia confers lasting histological and behavioral protection
      against severe global cerebral ischemia. However, functional abnormalities may be
      compensated for by undamaged brain regions and thus not detected by behavioral
      tests. To determine whether hypothermia preserves CA1 functional integrity, we
      measured synaptic and membrane properties of CA1 neurons in ischemic gerbils
      treated with postischemic hypothermia. METHODS: Gerbils were subjected to 5
      minutes of forebrain ischemia and were either left untreated or exposed to 2 days
      of hypothermia (32 degrees C for 24 hours and then 34 degrees C for 24 hours).
      Sham animals were operated on but not made ischemic, then either allowed to
      recover at room temperature or subjected to hypothermia for 2 days. Approximately
      5 weeks after ischemia or sham surgery, patch-clamp recordings were obtained from
      the CA1 region of hippocampal slices. RESULTS: There was approximately 95% CA1
      cell loss in untreated ischemic animals, whereas ischemic gerbils treated with
      hypothermia had cell counts similar to sham animals. Resting membrane potential,
      action potential amplitude and duration, input resistance, and synaptic currents
      evoked by Schaffer collateral stimulation were similar between pyramidal cells
      obtained from ischemic gerbils treated with hypothermia and sham-operated animals
      (P:>0.05). CONCLUSIONS: These data demonstrate that postischemic hypothermia
      preserves the measured electrophysiological properties of CA1 neurons in the
      absence of any apparent functional abnormalities. This study provides further
      support for the use of hypothermia as a treatment for cerebral ischemia.

PMID- 11239204
TI  - Postischemic estrogen reduces hypoperfusion and secondary ischemia after
      experimental stroke.
AB  - BACKGROUND AND PURPOSE: Estrogen is a known neuroprotective and vasoprotective
      agent in experimental cerebral ischemia. Preischemic steroid treatment protects
      animals of both sexes from focal cerebral ischemia. This study determined whether
      intravenous estrogen acts as a vasodilator when administered on reperfusion and
      whether the resulting increase in cerebral blood flow (CBF) provides tissue
      protection from middle cerebral artery occlusion. METHODS: Adult male Wistar rats
      were treated with reversible middle cerebral artery occlusion (2 hours), then
      infused with intravenous estrogen (Premarin; 1 mg/kg) or vehicle during the first
      minutes of reperfusion (n=15 per group). Cortical laser-Doppler flowmetry was
      used to assess adequacy of occlusion. Ischemic lesion volume was determined at 22
      hours after occlusion by 2,3,5-triphenyltetrazolium chloride staining and image
      analysis. Cortical and striatal CBF was measured by (14)[C]iodoantipyrine
      autoradiography at 10 (n=10) or 90 (n=11) minutes of reperfusion. RESULTS: As
      expected, supraphysiological plasma estrogen levels were achieved during
      reperfusion (estrogen, 198+/-45 pg/mL; vehicle, 6+/-5; P:=0.001). Physiological
      variables were controlled and not different between groups. Total hemispheric
      infarction was reduced in estrogen-treated rats (estrogen, 49+/-4% of ipsilateral
      structure; vehicle, 33+/-5%; P:=0.02), which was most pronounced in striatum
      (estrogen, 40+/-6% of ipsilateral striatum; vehicle, 60+/-3%; P:=0.01). CBF
      recovery was strikingly increased by estrogen infusion at 10 minutes in frontal
      (estrogen, 102+/-12 mL/100 g per minute; vehicle, 45+/-15; P:=0.01) and parietal
      cortex (estrogen, 74+/-15 mL/100 g per minute; vehicle, 22+/-13; P:=0.028) and
      throughout striatum (estrogen, 87+/-13 mL/100 g per minute; vehicle, 25+/-20;
      P:=0.02). Hemispheric volume with low CBF recovery (eg, <20 mL/100 g per minute)
      was smaller in estrogen-treated animals (estrogen, 73+/-18 mm(3); vehicle, 257+/
      46; P:=0.002). However, differences in CBF recovery could not be appreciated
      between groups by 90 minutes of reperfusion. CONCLUSIONS: Acute estrogen therapy
      during reperfusion improves tissue outcome from experimental stroke. The steroid
      rapidly promotes CBF recovery and reduces hemispheric no-reflow zones. This
      beneficial effect appears only during early reperfusion and likely complements
      other known mechanisms by which estrogen salvages brain from focal necrosis.

PMID- 11239205
TI  - Atrial fibrillation and stroke : concepts and controversies.

PMID- 11239206
TI  - Life-threatening complications of spinal manipulation.

PMID- 11239207
TI  - Osmotherapy: a call to arms.

PMID- 11239208
TI  - Association of intraoperative transcranial Doppler monitoring variables with
      stroke from carotid endarterectomy.

PMID- 11239209
TI  - Decompressive craniectomy for early therapy and secondary prevention of cerebral
      infarction.

PMID- 11239210
TI  - Recommendations for the management of patients with unruptured intracranial
      aneurysms.

PMID- 11239211
TI  - Guidelines for stroke center development.

PMID- 11239212
TI  - Cerebral infarction throughout both internal carotid arteries detected by
      diffusion-weighted MRI.

PMID- 11239213
TI  - Impact of cerebral microcirculatory changes on cerebral blood flow during
      cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

PMID- 11239214
TI  - Transfusion Medicine Illustrated. RBC rosetting and erythrophagocytosis in adult
      paroxysmal cold hemoglobinuria.

PMID- 11239216
TI  - Blood donations, safety, and incentives.

PMID- 11239217
TI  - Mobilized PBPC concentrates: a maturing blood component.

PMID- 11239218
TI  - The potential impact of incentives on future blood donation behavior.
AB  - BACKGROUND: It is important to assess the potential efficacy and safety of
      offering donation incentives as part of recruitment and retention programs. STUDY
      DESIGN AND METHODS: In 1995, 7489 allogeneic donors responded to an anonymous
      mail survey that inquired about demographics, donation history, infectious
      disease risks, and the potential appeal of incentives. RESULTS: The projected net
      effect of offering blood credits and medical testing would be to motivate,
      respectively, 58 percent and 46 percent of donors to return, whereas offering an
      item of limited value would motivate 20 percent to do so. First-time and younger
      donors reported more frequently than repeat or older donors that incentives would
      appeal to them. Donors attracted by cash were 60 percent more likely to have a
      risk for transfusion-transmissible infections (p = 0.03). Although not
      statistically significant, the odds of being an at-risk donor were higher among
      individuals attracted by tickets to events (OR 1.5) and extra time off work (OR
      1.2). CONCLUSION: These findings suggest that offering blood credits and (though
      to a lesser extent) items of limited value could be safe and effective strategies
      for retaining donors. Although medical tests were found to have broad appeal,
      studies are needed to identify tests in which donors would be most interested.

PMID- 11239219
TI  - The variability of compensatory erythropoiesis in repeated autologous blood
      donation.
AB  - BACKGROUND: Compensatory RBC production during repeated preoperative autologous
      blood donation (PABD) shows marked interindividual variability. This study was
      performed to reveal variables that might be useful to predict the amount of the
      erythropoietic response to PABD in an individual patient who was not iron
      deficient. STUDY DESIGN AND METHODS: In a retrospective study, 104 adult
      patients, 48 women and 56 men (mean age, 59.9 years; range, 18-82 years) who
      donated 3 units (450 mL) of autologous blood at weekly intervals for major
      surgery were investigated. Blood counts, ferritin, and net preoperative RBC
      production (net RBC production) were determined in all patients, and soluble
      transferrin receptor and endogenous levels of EPO, SCF, and IL-1beta were
      measured in 63 patients. Multiple linear regression analysis was used to
      determine whether the variance of net RBC production was attributable to baseline
      values of these variables. RESULTS: Net RBC production was not different in
      patients who received oral iron and patients who did not (384 +/- 222 mL vs. 356
      +/- 158 mL). In both groups, the same two variables consistently showed a
      significant relationship to net RBC production: the length of the period between
      the third donation and the last visit was positively related (p = 0.00001 vs. p =
      0.0002) and the Hct at baseline was negatively related (p = 0.0002 vs. p = 0.02)
      with net RBC production. The proportion of variance in net RBC production that
      was attributable to these two variables was 48.1 percent (r(2) = 0.481) and 34.9
      percent (r(2) = 0.349), respectively. CONCLUSION: RBC production after PABD
      increases with increasing interval from last donation to surgery. This suggests
      that the interval from last donation to surgery should be maximized. This can be
      achieved by organizational measures in combination with the preparation of RBC
      concentrates in additive solution with a maximum shelf life.

PMID- 11239220
TI  - Spleen enlargement in healthy donors during G-CSF mobilization of PBPCs.
AB  - BACKGROUND: Recombinant human G-CSF is widely used to mobilize PBPCs in healthy
      donors for allogeneic transplantation. There have been concerns about donor
      safety because of splenic ruptures during G-CSF application. To address this
      problem, changes in splenic size in 91 healthy donors during G-CSF mobilization
      of allogeneic PBPCs were investigated. STUDY DESIGN AND METHODS: For
      mobilization, G-CSF in a dosage of 7.5 microg per kg per day was administered for
      5 days and PBPC collection started Day 5. Splenic size was determined by
      ultrasound before G-CSF application was started and on the day of the first
      apheresis. RESULTS: The mean increase in splenic length was 11 mm (range, 0-28
      mm; p<0.0001), whereas a mean increase of 5 mm in width (range, 0-14 mm;
      p<0.0001) was measured. No major side effects could be observed. There was no
      significant correlation between the increase in splenic size and the hematologic
      values, or the age and body-mass index. In a multivariant analysis, no
      independent risk factor for the development of a spleen enlargement over 19 mm in
      length and 9 mm in thickness was found in 20 percent of investigated donors.
      CONCLUSION: In this prospective trial, a significant spleen enlargement was
      observed in healthy donors during G-CSF mobilization of allogeneic PBPCs. Further
      investigations are needed to define the degree of spleen enlargement with higher
      G-CSF dosages to improve donor safety.

PMID- 11239221
TI  - CD34+ cell mobilization for allogeneic progenitor cell transplantation: efficacy
      of a short course of G-CSF.
AB  - BACKGROUND: G-CSF-mobilized PBPCs are considered the richest source of HPCs for
      both autologous and allogeneic transplantation, but, despite their wide use, the
      best dose and schedule for G-CSF administration have not been definitively
      established. STUDY DESIGN AND METHODS: With a target of collecting from the
      peripheral blood > or = 4 x 10(6) CD34+ cells per kg of body weight of the
      recipient, the short-course administration of glycosylated G-CSF (gly-G-CSF) in
      30 healthy donors for an allogeneic transplantation was investigated. Gly-G-CSF
      was given subcutaneously at a dose of 10 microg per kg per day in two divided
      doses over 3 days and was followed by a leukapheresis (on the 4th day) 12 hours
      after the last dose. RESULTS: A median of 53.5 circulating CD34+ cells per microL
      (range, 19-190) was found in the 30 donors on the day of first leukapheresis,
      which allowed a median CD34+ cell collection of 6.0 x 10(6) per kg of body weight
      of the donor and 6.5 x 10(6) per kg of body weight of the recipient. In 25 (83%)
      of 30 donors, a single procedure was sufficient to collect the target CD34+
      cells, while in the other 5, two leukapheresis procedures were required.
      Hematologic reconstitution was observed in all patients at a median of 14 days
      (range, 10-23) for neutrophils and 14.5 days (range, 11-46) for platelets. With a
      median infusion of 3.9 x 10(8) CD3+ T-lymphocytes per kg of body weight of the
      recipient (range, 1.3-7.8), acute and chronic GVHD occurred in 13 (43%) of 30 and
      15 (60%) of 25 evaluable patients, respectively. After a median follow-up of 337
      days from transplant, 22 (73%) of 30 patients are alive in complete remission.
      CONCLUSION: A schedule consisting of 3-day administration of gly-G-CSF followed
      by a single leukapheresis can be proposed and widely accepted by healthy donors,
      as 84 percent of them reach the target in the estimated time with a reduced drug
      exposure. The cost of the procedure is reduced, in terms of both the growth
      factor administration and the number of leukapheresis procedures. The search for
      the optimum methods of donor management may improve the acceptability of this
      procedure and increase the number of allogeneic transplantations from PBPCs.

PMID- 11239222
TI  - PBPC mobilization with paclitaxel, ifosfamide, and G-CSF with or without
      amifostine: results of a prospective randomized trial.
AB  - BACKGROUND: The impact of amifostine on PBPC mobilization with paclitaxel and
      ifosfamide plus G-CSF was assessed. STUDY DESIGN AND METHODS: Forty patients with
      a median age of 34 years (range, 19-53) who had germ cell tumor were evaluated
      for high-dose chemotherapy. Patients were randomly assigned to receive either a
      single 500-mg dose of amifostine (Group A, n = 20) or no amifostine (Group B, n =
      20) before mobilization chemotherapy with paclitaxel (175 mg/m(2)) given over 3
      hours and ifosfamide (5 g/m(2)) given over 24 hours (TI) on Day 1. G-CSF at 10
      microg per kg per day was given subsequent to TI with or without amifostine from
      Day 3 until the end of leukapheresis procedures. RESULTS: In 2 (10%) of 20
      patients receiving amifostine and 3 (15%) of 20 patients not receiving it, no
      PBPC separation was performed because of mobilization failure. No significant
      differences were observed in the study arms with regard to the time from
      chemotherapy until first PBPC collection or the number of apheresis procedures
      needed to harvest more than 2.5 x 10(6) CD34+ cells per kg. Furthermore,
      leukapheresis procedures yielded comparable doses of CD34+ cells per kg (3.4 x
      10(6) vs. 3.6 x 10(6); p = 0.82), MNCs per kg (2.7 x 10(8) vs. 2.6 x 10(8); p =
      0.18), and CFU-GM per kg (15.9 x 10(4) vs. 19.3 x 10(4); p = 0.20). Patients in
      Group A had higher numbers of circulating CD34+ cells on Day 10 (103.0/microL vs.
      46.8/microL; p = 0.10) and on Day 11 (63.0/microL vs.14.3/microL; p = 0.04) than
      did patients in Group B. CONCLUSION: Administration of a single dose of
      amifostine before chemotherapy with TI mobilized higher numbers of CD34 cells in
      the circulation, but did not enhance the overall collection efficiency in the
      present trial.

PMID- 11239223
TI  - Donor age-related differences in PBPC mobilization with rHuG-CSF.
AB  - BACKGROUND: Data on the administration of rHuG-CSF to normal donors <18 years old
      are very limited. STUDY DESIGN AND METHODS: The results of rHuG-CSF
      administration to 61 donors <18 years old (Group A) were retrospectively
      evaluated and compared with results from 353 donors > or = 18 years old (Group B)
      who are included in the Spanish National Donor Registry. The mean age (range) in
      Group A and B was 14 (1-17) and 38 (18-71) years, respectively (p<0.001). The
      mean dose of rHuG-CSF was 10 microg per kg per day (range, 9-16) during a mean of
      5 days (range, 4-6). Central venous access was placed more frequently in younger
      donors (25% vs. 6%; p<0.001). RESULTS: The mean number of CD34+ cells collected
      was 7.6 and 6.9 x 10(6) per kg of donor's body weight in Group A and B,
      respectively. Fifty-six percent of Group A donors needed only one apheresis to
      achieve > or = 4 x 10(6) CD34+ cells per kg versus 39 percent of Group B donors
      (p = 0.01). Side effects were more common in Group B (71% vs. 41%; p<0.001).
      CONCLUSION: The administration of rHuG-CSF to donors <18 years old leads to CD34+
      cell mobilization in a pattern similar to that observed in adults. Greater age
      was associated with a more frequent requirement for more than one apheresis to
      achieve a similar number of CD34+ cells.

PMID- 11239224
TI  - Cytokines and vascular cell adhesion molecule-1 in the blood of patients
      undergoing HPC mobilization.
AB  - BACKGROUND: The mechanism of HPC mobilization in humans is unclear. In this
      study, the relationship between PBPC mobilization and blood levels of G-CSF,
      endogenous cytokines (IL-8, SCF, thrombopoietin [TPO]), and the vascular cell
      adhesion molecule-1 (VCAM-1) was analyzed in patients with malignancy who were
      undergoing a PBPC mobilization regimen. STUDY DESIGN AND METHODS: Fifty-four
      patients with multiple myeloma (MM) and 29 with breast cancer (BC) underwent a
      mobilization regimen combining conventional chemotherapy and G-CSF up to the last
      day of PBPC collection. The CD34+ cell count was determined on each day when
      leukapheresis was scheduled. Venous blood samples (n = 117) were drawn before
      apheresis for CD34+ cell count (flow cytometry) and cytokine (G-CSF, IL-8, SCF,
      TPO) and VCAM-1 measurements (ELISA). RESULTS: In multiple regression analysis,
      SCF was a significant determinant of CD34+ cell levels in BC patients (R = 0.50,
      p = 0.03) and of VCAM-1 levels in MM patients (R = 0.32, p = 0.02). SCF was
      negatively correlated with CD34+ cell count in patients with BC. SCF and VCAM-1
      blood levels were correlated in MM and BC patients. CONCLUSION: SCF and VCAM-1
      could play a role in PBPC mobilization in patients and could be useful measures
      by which to study patients undergoing a mobilization regimen.

PMID- 11239225
TI  - Umbilical cord blood progeny cells that retain a CD34+ phenotype after ex vivo
      expansion have less engraftment potential than unexpanded CD34+ cells.
AB  - BACKGROUND: Because of the limitation of cell numbers associated with cord blood
      harvests, there is a need to determine the efficacy of using ex vivo-expanded
      cord blood cells in a transplantation setting. In this study, limiting-dilution
      analysis was used in nonobese diabetic mice with severe combined immunodeficiency
      (NOD/SCID) to compare the engraftment potential of progeny cells expressing the
      CD34+ phenotype after expansion with that of uncultured CD34+ cells. STUDY DESIGN
      AND METHODS: Cord blood CD34+ cells were cultured in Iscove's modified Dulbecco
      medium supplemented with 10-percent fetal calf serum (FCS) and IL-6, SCF,
      megakaryocyte growth and development factor, and Flt3 ligand. The resulting ex
      vivo-expanded products were assessed for total numbers of nucleated cells, CD34+
      cells, and CFUs and long-term culture-initiating cell activity. The engraftment
      potentials of cultured progeny CD34+ cells and uncultured CD34+ cells were
      determined by using NOD/SCID mice. RESULTS: After 14 days of culture, total
      nucleated cell counts increased over input values by 180 +/- 59-fold, CD34+ cell
      numbers by 44 +/- 13-fold, CFU activity by 23 +/- 5-fold, and long-term culture
      initiating cell activity by 20 +/- 6-fold (mean +/- SD; n = 6). The frequency of
      SCID-repopulating cells (SRC) in mice transplanted with uncultured products was 1
      per 20,000 CD34+ cells (95% CI, 1:10,000-1:38,000) and that in mice receiving ex
      vivo-expanded products was 1 per 418,000 progeny CD34+ cells (95% CI, 1:158,000
      1:1,100,000). Taken together, these data indicated that, after 2 weeks of
      culture, there was a modest twofold increase in the total number of SRCs.
      However, the levels of human CD45 cell engraftment in NOD/SCID recipients of
      progeny CD34+ cells were significantly lower than those in mice receiving
      equivalent numbers of uncultured CD34+ cells (p<0.05). CONCLUSION: Umbilical cord
      blood progeny cells retaining a CD34+ phenotype after ex vivo expansion have less
      engraftment potential than do unexpanded CD34+ cells.

PMID- 11239226
TI  - Absence of immunopathology associated with repeated IV administration of bovine
      Hb-based oxygen carrier in dogs.
AB  - BACKGROUND: A Hb-based oxygen carrier, HBOC-301, is licensed by the FDA for use
      as a single-dose product to treat anemia in canines. The objective of this study
      was to investigate the immunopathologic consequences of multiple doses of HBOC
      301. STUDY DESIGN AND METHODS: HBOC-301 was administered intravenously at 1.3 g
      per kg (10 mL/kg) nine times over 50 weeks to each of eight splenectomized
      beagles. During interim weeks, HBOC-301-specific IgG antibody was quantified in
      serum by immunoassay. Immunofluorescence studies were performed on thin sections
      of control and test dog livers and kidneys to detect any IgG, IgM, IgA, or C3
      deposition. Physiology (p50) studies evaluated the capacity of circulating HBOC
      301-specific IgG antibody to competitively block the binding of oxygen to HBOC
      301. RESULTS: HBOC-301-specific IgG antibody was detected in seven of eight HBOC
      301-treated dogs by Week 6. Peak antibody levels occurred by Week 10 (after the
      third dose). Immunofluorescence studies detected comparable IgG, IgA, IgM, or C3
      deposition patterns in the kidneys and livers of both control and test dogs,
      which indicated no selective antibody-mediated deposition from multiple HBOC-301
      administrations. Moreover, HBOC-301-specific IgG antibody in serum was unable to
      inhibit oxygen binding to the HBOC-301 in vitro, which indicated that circulating
      antibody did not diminish the oxygen-binding capacity of HBOC-301. CONCLUSION:
      The immunologic, histologic, and physiologic data support the safety of multidose
      administration of HBOC-301 in canines.

PMID- 11239227
TI  - Effects of three Hb-based oxygen-carrying solutions on neutrophil activation in
      vitro: quantitative measurement of the expression of adherence receptors.
AB  - BACKGROUND: Hb-based oxygen carriers (HbOCs) are currently under investigation as
      RBC substitutes. These solutions have vasoactive properties and may modify the
      behavior of the RBC in vitro. The effects of these agents on other blood cells
      have not been extensively investigated. The aim of this study was to evaluate the
      potential effect(s) of three differently modified HbOCs on the activation of
      PMNs. STUDY DESIGN AND METHODS: Whole blood from humans was incubated with Hb
      dextran-benzene-tetracarboxylate, alphaalpha-Hb, or o-raffinose-poly-Hb for 15,
      30, and 60 minutes. The expression of adherence receptors CD62L, CD18, and CD11b,
      which reflects the activation state of the neutrophils, was assessed in vitro by
      a direct immunofluorescence method using calibration beads measured by flow
      cytometry. RESULTS: The observed expression of each of the three adherence
      receptors for each solution at each time point was similar to that noted with the
      RPMI control. Decreases in CD62L and increases in CD18 expression were noted at
      15 minutes of incubation but, when those values were compared to the values
      obtained with TNFalpha as the positive control of PMN activation, the profile of
      expression of adherence receptors obtained with HbOC solutions did not conform to
      the expected activation profile of PMNs. CONCLUSION: Hb solutions modified by a
      variety of methods, as obtained and employed in this study, did not appear to
      activate neutrophils in vitro.

PMID- 11239228
TI  - A novel, automated method of temperature cycling to produce cryoprecipitate.
AB  - BACKGROUND: Cryoprecipitate continues to find wide application in transfusion
      practice. Current AABB standards call for a minimum of 80 units (U) of factor
      VIII and 150 mg of fibrinogen per bag of cryoprecipitate. However, individual
      cryoprecipitates can vary greatly in content, with as many as 20 different
      factors known to affect the yield. STUDY DESIGN AND METHODS: Plasma was processed
      in a new, rapid, automated device (CryoSeal, Thermogenesis) with computer
      controlled temperature cycling to produce cryoprecipitate. RESULTS: In repeat
      runs (n = 20), the automated procedure yielded a product containing 184 mg of
      fibrinogen and 158 U of factor VIII in 55 minutes. Additional studies using
      plasma pools to compare the quality of the machine-generated products to those of
      traditionally prepared cryoprecipitate showed comparative recoveries of 182 and
      187 mg of fibrinogen and 172.1 and 129.7 U of factor VIII and no significant
      difference in the levels of plasminogen, protein C, or protein S. CONCLUSION: The
      new system offers an automated method of cryoprecipitate production in which the
      steps involved in temperature cycling are initiated sequentially, producing
      within 1 hour a preparation that is equivalent to standard cryoprecipitate.

PMID- 11239229
TI  - Effect of gamma radiation on the in vitro aggregability of WBC-reduced apheresis
      platelets.
AB  - BACKGROUND: The effect of gamma radiation on single-donor apheresis platelet
      concentrates (SDPs) has been elucidated only incompletely. The only existing
      report on the function of SDPs stored in the irradiated state found a
      deterioration in the in vitro aggregability at the end of shelf life in SDPs
      divided before irradiation with 1500 cGy. STUDY DESIGN AND METHODS: The in vitro
      properties of platelets were examined in four series of irradiated and control
      platelets, each obtained from the same 15 donors. Irradiation with 3000 cGy was
      performed on Days 0, 3, and 5. Cellular content, aggregability by ADP alone or
      ADP and epinephrine, spontaneous and induced CD62 expression, beta
      thromboglobulin release, glucose consumption, lactate production, and pH were
      measured immediately after preparation and on Days 3 and 5 after donation.
      RESULTS: Comparable in vitro properties were measured in irradiated and control
      platelets, whether irradiation was performed on Day 3 or Day 5. However, in
      platelets irradiated on Day 0, we found a significantly better in vitro
      aggregability by 20 microM: ADP immediately after irradiation and by 10 microM:
      ADP and 2 microM: epinephrine at the end of shelf life than was found in the
      other groups (Day 5 results: Day 0 irradiation: 75 +/- 32%; Day 3 irradiation: 45
      +/- 45%; Day 5 irradiation: 47 +/- 41%; control: 40 +/- 24%; p<0.05). CONCLUSION:
      Gamma radiation had no adverse effect on platelet quality in extremely WBC
      reduced SDPs. On the contrary, a slight, but significantly better in vitro
      aggregability was found in SDPs irradiated before storage than in platelets
      irradiated later during storage and in unirradiated platelets. This increased in
      vitro aggregability persisted until the end of shelf life.

PMID- 11239230
TI  - Platelet storage lesion of WBC-reduced, pooled, buffy coat-derived platelet
      concentrates prepared in three in-process filter/storage bag combinations.
AB  - BACKGROUND: With the implementation of universal WBC reduction in the United
      Kingdom, in-process WBC-reduction filters for pooled buffy coat (BC)-derived
      platelet concentrates (PCs) are used in routine production. The effects of three
      filter/storage bag combinations on platelet activation and microvesiculation and
      on the activation of coagulation were investigated. STUDY DESIGN AND METHODS:
      Using pooled BCs from the same donors, three filter/storage bag combinations
      (Autostop BC/CLX, Pall Biomedical; Sepacell PLX5/PL2410, Asahi Medical; and
      Imugard III-PL 4P/Teruflex, Terumo) were compared with unfiltered controls for
      their effects on microvesiculation and other storage-induced changes in
      platelets. Process efficiency was measured by platelet yield and residual WBC
      count. The storage changes were assessed: pH, activation of platelets measured by
      CD62P on the platelet surface and in supernatant plasma, quantitation of platelet
      derived and RBC-derived microvesicles, cellular injury measured by annexin V in
      the supernatant plasma, and activation of the coagulation system measured by
      kallikrein-like and thrombin-like activities, prothrombin fragment 1+2, and
      thrombin-antithrombin complex. RESULTS: All three filters were comparable in
      terms of platelet recovery and WBC removal, and none induced immediate platelet
      activation or microvesiculation. With storage, platelet activation or
      microvesiculation increased in platelets prepared by all three filters and in
      unfiltered controls, but these effects were significantly less in the Imugard PCs
      than in controls. These findings were consistent with those for annexin V in the
      supernatant plasma, which were lower in Imugard PCs than in other products.
      Sepacell and Imugard filters reduced RBC-derived microvesicles to 50 percent of
      control levels, but the Autostop filter had no effect. On storage, levels of RBC
      derived microvesicles in filtered products remained static, but levels in the
      unfiltered control doubled. Kallikrein- and thrombin-like activities were
      generated only by the Autostop filter without any further increment on storage.
      CONCLUSION: WBC-reduced pooled BC-PCs prepared by various filter/bag combinations
      were equivalent on Day 1 but differed during storage in terms of platelet
      activation or microvesiculation.

PMID- 11239231
TI  - Long-term survival in transfusion recipients in Sweden, 1993.
AB  - BACKGROUND: Survival and characteristics of transfusion recipients have not been
      studied enough, although they represent key measures in cost-effectiveness
      analyses of various donor screening procedures. STUDY DESIGN AND METHODS:
      Hospital and blood bank records were collected on all patients in Orebro County,
      Sweden, from March through May 1993 (1111 transfusion episodes) and a random
      sample from Stockholm County during April 1993 (793 transfusion episodes). All
      patients were then matched with the national register of deaths in Sweden during
      a follow-up period of 40 months. RESULTS: The median patient age was 71 years and
      the median transfusion total was 2 units. Only 35 percent of the patients were
      under the age of 65, 9 percent under 40, and 1.6 percent under 1 year. About half
      (56%) were women. Among the Orebro patients, 47 percent were surgical and 29
      percent internal medicine patients. Of 1720 patients whose survival could be
      investigated, 66 percent were alive after 1 year and 51 percent after 40 months.
      The survival rates were rather similar in patients receiving RBCs and plasma but
      lower in those receiving platelets. CONCLUSION: The survival of patients
      transfused in Sweden in 1993 differered significantly from estimations based on
      studies from the 1980s. This difference has major implications for the
      estimations of cost-effectiveness of blood donor screening for infectious agents.

PMID- 11239232
TI  - Mathematical modeling and computer simulation of erythrocytapheresis for SCD.
AB  - BACKGROUND: Erythrocytapheresis is used to prevent acute chest syndrome and
      stroke in patients with sickle cell disease (SCD). However, such regimens are
      associated with significant risks, such as iron overload and potential exposure
      to transfusion-transmitted infectious diseases. Computer modeling of
      erythrocytapheresis procedures may help optimize treatments and minimize risks.
      STUDY DESIGN AND METHODS: Mathematical models based upon material balance
      equations and patient-specific statistical analyses were developed to estimate
      HbS levels immediately after erythrocytapheresis and immediately before the next
      treatment. The equations were incorporated into a software application that was
      used to model the effects of various treatment values on four patients treated
      with 90 erythrocytapheresis procedures. RESULTS: Immediate postprocedure HbS
      values were accurately estimated with correlations between measured and
      calculated values ranging from R(2) = 0.83 to 0.96. Estimates of HbS just before
      the next treatment correlated well in three patients (R(2) = 0.71 to 0.83) but
      poorly in one (R(2) = 0.28 to 0.46). Varying the treatment values by computer
      simulation led to a wide variation in the number of RBC units and the net RBC
      volume transfused. CONCLUSION: Computer modeling of erythrocytapheresis can be
      used to optimize chronic treatment regimens for SCD patients and potentially to
      minimize the risks of overtransfusion.

PMID- 11239233
TI  - Transfusion-related acute lung injury after the infusion of IVIG.
AB  - BACKGROUND: Transfusion-related acute lung injury (TRALI) is a well
      characterized, serious complication of blood component therapy in hospitalized
      patients. The signs and symptoms are often attributed to other clinical aspects
      of a patient's condition, and therefore TRALI may go unrecognized. IVIG is a
      pooled plasma derivative commonly used in the outpatient setting. Respiratory
      complications of IVIG infusion have typically been attributed to volume overload
      or allergic and vasomotor reactions. TRALI has never been documented to occur
      after IVIG infusion. CASE REPORT: A 23-year-old man with multifocal motor
      neuropathy developed noncardiogenic pulmonary edema 6 hours after receiving 90 g
      of IVIG by a rapid-infusion protocol. He fully recovered in 5 days with nasal
      oxygen and bed rest. Granulocyte-associated IgG was detected in his blood 14 and
      27 weeks after the event. The lots of IVIG that he received were found to contain
      a low-titer, panreactive, granulocyte antibody, mostly IgG. CONCLUSION: This is
      the first documented case of TRALI after IVIG infusion. An autoimmune syndrome,
      including autoantibody-coated granulocytes, may have been a priming stimulus for
      granulocyte interaction with pulmonary capillary endothelium. Rapid infusion of a
      large quantity of granulocyte antibody may have precipitated TRALI. A pooled
      plasma product or derivative may result in TRALI.

PMID- 11239234
TI  - The low-incidence MNS antigens M(v), s(D), and Mit arise from single amino acid
      substitutions on GPB.
AB  - BACKGROUND: GPB carries 'N' at its N:-terminus and S and s, determined by a
      polymorphism at amino acid position 29 (Met29Thr). The low-incidence antigens
      M(v), s(D), and Mit are associated with weakened expression of S and/or s, and
      the purpose of this study was to define their molecular bases. METHODS: The GPB
      gene (GYPB) was sequenced after RT-PCR of RNA from four samples: two M(v)+, one
      s(D)+, and one Mit+. The point mutations observed were confirmed by sequencing of
      genomic DNA from these and other examples of s(D)+ and Mit+ samples. RESULTS: A
      point mutation of 65C>G observed in the M(v)+ samples predicted a change of
      Thr3Ser. A mutation of C>G at nucleotide 173 of the GYPB coding sequence,
      observed in two s(D)+ samples, predicted a change of Pro39Arg. Three Mit+ samples
      showed a nucleotide substitution of 161G>A, which predicted a change of Arg35His.
      Altered expression of S or s was confirmed by serologic tests. CONCLUSION: These
      results confirm that Arg35 is important for full expression of S. Pro39 and,
      surprisingly, Thr3 are also important for full expression of s. Furthermore, Thr3
      must be essential for expression of 'N,' as M(v)+ RBCs lack 'N.'

PMID- 11239235
TI  - Quantitation of genomic DNA in plasma and serum samples: higher concentrations of
      genomic DNA found in serum than in plasma.
AB  - BACKGROUND: Plasma and serum samples have been used to detect cell-free genomic
      DNA in serum or plasma in certain pathologic conditions such as systemic lupus
      erythematosus, pulmonary embolism, and malignancies, as well as in fetal cell
      chimerisms in maternal serum and/or plasma. In this study, baseline
      concentrations of cell-free DNA in serum and plasma samples were evaluated for
      the study of posttransfusion chimerism. STUDY DESIGN AND METHODS: DNA was
      extracted from fresh or stored (4 degrees C for 1-6 days) normal donor serum or
      plasma samples (ACD; EDTA) by using reagents from an HIV assay kit. After
      incubation and washing of samples, purified DNA was amplified with HLA DQ-alpha
      primers (GH26 and 27) or human Y-chromosome primers (SA and SD) to quantitate the
      concentration of genomic DNA. RESULTS: Fresh serum samples had concentrations of
      cell-free DNA that were about 20-fold higher than the concentrations in fresh
      plasma samples. The concentration of cell-free genomic DNA in serum samples
      increased daily, to a level more than 100 times baseline after clotted blood
      tubes were stored at 4 degrees C for 4 to 5 days. There was a small increase in
      cell-free plasma DNA in stored ACD whole blood samples. Male WBCs, spiked into
      fresh nonanticoagulated female blood, were lysed during the process of clotting,
      with male DNA liberated into the serum samples. CONCLUSION: Most cell-free DNA in
      serum samples is generated during the process of clotting in the original
      collection tube. The concentration of cell-free genomic DNA in fresh plasma is
      probably the same as that in circulation. Consequently, while serum samples
      should not be used to monitor the concentration of cell-free DNA in a patient's
      circulation, serum collected from sample tubes containing clots (i.e., without
      anticoagulant), 3 to 5 days after the date of phlebotomy, could be useful as a
      source of DNA with which to screen for posttransfusion microchimerism.

PMID- 11239236
TI  - Canada's transfusion medicine pioneer: Lawrence Bruce Robertson.

PMID- 11239237
TI  - Progress in the development of RBC substitutes.

PMID- 11239238
TI  - Effect of storage time on filter performance.

PMID- 11239239
TI  - Is airport malaria a transfusion-transmitted malaria risk?

PMID- 11239240
TI  - Relationship between gestational age and cord blood quality.

PMID- 11239241
TI  - NAT and blood safety.

PMID- 11239242
TI  - Detection of HCV core antigen in HCV RNA positive, anti-HCV negative blood
      donations from Polish blood donors.

PMID- 11239243
TI  - Lactose supports Muller cell protein expression patterns in the absence of the
      retinal pigment epithelium.
AB  - PURPOSE: We have previously shown that lactose, but not mannose, promotes the
      assembly of nascent photoreceptor outer segments in the absence of the retinal
      pigment epithelium (RPE). The purpose of the present study was to determine if,
      in addition to the improved outer segment assembly observed in the presence of
      lactose, biosynthetic changes in Muller cells could also be detected. METHODS:
      The RPE was removed from intact isolated Xenopus embryonic eyes that were allowed
      to complete differentiation in Niu-Twitty medium, Niu-Twitty with mannose, or Niu
      Twitty with lactose. Control retinas matured in vitro with an adherent RPE.
      Retinal morphology was evaluated for organized folding of outer segment membranes
      and cell loss. In addition, the expression of three Muller cell proteins, glial
      fibrillary acidic protein (GFAP), cellular retinaldehyde-binding protein
      (CRALBP), and glutamine synthetase, was examined. RESULTS: In control retinas,
      GFAP is undetectable, CRALBP heavily immunolabels Muller cells, and radial
      patterns of glutamine synthetase immunoreactivity are present. In the absence of
      the RPE, Muller cells upregulate GFAP expression, CRALBP labeling is present at a
      slightly reduced level, and glutamine synthetase immunolabeling is negligible.
      Neither mannose nor lactose modify significantly the expression of CRALBP.
      Similarly, both compounds completely prevent the upregulation of GFAP. However,
      normal glutamine synthetase expression was observed only in the presence of
      lactose, but not in the presence of mannose. Statistical analyses of slot blot
      based protein quantification confirmed our immunochemical results. CONCLUSIONS:
      In RPE-deprived retinas supplemented with lactose, Muller cells were
      morphologically normal. The proper photoreceptor outer segment morphogenesis
      observed under these conditions was uniquely associated with normal levels of
      glutamine synthetase expression. The exact significance of this finding with
      respect to photoreceptor outer segment morphogenesis is unknown. We suggest that
      glutamine synthetase may be a marker of Muller cell metabolic or structural
      integrity that may reflect the enhanced ability of these cells, in the presence
      of lactose, to support photoreceptor outer segment morphogenesis.

PMID- 11239244
TI  - Epitope-tagged recombinant AAV vectors for expressing neurturin and its receptor
      in retinal cells.
AB  - PURPOSE: Neurturin (NTN) is a potent neuronal survival factor in the central and
      peripheral nervous systems. We previously described altered expression of mRNAs
      for NTN and one of its receptor components, GFRa-2 in degenerative retinas of
      rd/rd mice. Towards assessing the potential for transfer of these genes to
      counteract retinal degeneration, we examined recombinant adeno-associated virus
      (rAAV) constructs for expression of NTN and GFRa-2 transgenes in retinal cells in
      vitro and for the effect of transgene expression on retinal function following
      intraocular delivery in rd/rd mice. METHODS: The rAAV constructs incorporated
      epitope tags to facilitate discrimination between transgenic and endogenous
      expression. Expression of murine NTN was driven by a CMV promoter and a partial
      murine opsin promoter was used to drive expression of human GFRa-2. rAAV
      preparations were used to infect mouse retinal cell cultures and for intraocular
      injection of predegenerative rd/rd mice. Endogenous and transgene expression was
      analyzed by immunofluorescence. Photoreceptor function in treated mice was
      assessed by electroretinography. RESULTS: Both vectors delivered and expressed
      their transgenes in vitro and in vivo. Differential targeting was achieved in
      vivo through the use of alternative promoters. Under the conditions examined, no
      functional rescue of rd photoreceptors was observed. CONCLUSIONS: Therapeutic
      treatment of the rd model of retinal degeneration does not appear to be effected
      by simple modulation of the expression of NTN or GFRa-2, and may therefore depend
      on additional synergistic factors. Our AAV constructs will facilitate the
      development of combinatorial approaches to the treatment of central and
      peripheral neurodegenerations.

PMID- 11239245
TI  - Calcium channel blocker D-cis-diltiazem does not slow retinal degeneration in the
      PDE6B mutant rcd1 canine model of retinitis pigmentosa.
AB  - PURPOSE: D-cis-diltiazem, a calcium channel blocker, has been reported to enhance
      photoreceptor survival in the rd mouse, a model of retinitis pigmentosa (RP)
      resulting from mutation of the PDE6B gene. We tested the hypothesis that
      diltiazem treatment would similarly rescue the canine rcd1 model of RP, which is
      also caused by a null mutation in the PDE6B gene. METHODS: D-cis-diltiazem was
      delivered orally twice daily to rcd1 affected dogs beginning at 4 weeks of age;
      untreated age-matched rcd1 dogs served as controls. At 14 weeks,
      electroretinograms (ERG) were performed on all animals; 14 dogs were euthanized
      at this age, and 2 dogs at 25 weeks of age. Eyes were enucleated, fixed, and
      processed for routine histological examination. RESULTS: No significant
      differences were found in ERG or histopathologic parameters between diltiazem
      treated and untreated rcd1 dogs. Neither rcd1 group showed a rod b-wave; ERGs
      evoked by single white flashes (dark- or light-adapted) and flicker were also
      identical between groups. Similarly, treated and untreated animals did not differ
      in the degree of preservation of the photoreceptor layer, confirmed in cell
      counts within the outer nuclear layer. CONCLUSIONS: Treatment of rcd1 affected
      dogs with D-cis-diltiazem did not modify the photoreceptor disease when results
      were assessed using either ERG or histopathologic criteria. The positive
      photoreceptor-rescue effect of calcium channel blockers reported in the rd mouse
      was thus not generalizable to another species with retinal degeneration due to
      mutation in the PDE6B gene. Caution needs to be exerted in extrapolation to the
      comparable human forms of RP.

PMID- 11239246
TI  - Retinal uptake of intravitreally injected Hsc/Hsp70 and its effect on
      susceptibility to light damage.
AB  - PURPOSE: To evaluate the uptake by the rat retina of an intravitreally injected
      mixture of the constitutive and inducible forms of the 70 kD heat shock protein
      (Hsc/Hsp70) and test its potential to protect photoreceptors from light damage.
      METHODS: Hsc/Hsp70 and actin (control protein) were labeled with fluorescein
      (referred to as fl-Hsc/Hsp70 and fl-actin). The labeled proteins were
      microinjected intravitreally into the normal or light damaged rat eye and each
      eye collected at three intervals after the injections. Retinal uptake of
      Hsc/Hsp70 or actin was studied in frozen sections using epifluorescence
      microscopy and in western blots of retinal homogenates using an anti-fluorescein
      antibody. Additionally, the cytoprotective effects of Hsc/Hsp70 were tested in
      rats that first were exposed to bright light (170 ft-c) for 24 h and then given
      an intravitreal injection of the protein immediately thereafter. Ten days later,
      photoreceptor damage was evaluated by measuring the area of the outer nuclear
      layer at fixed locations along the circumference of the retina. RESULTS: The
      fluorescein-labeled proteins were detected in the retina one h after
      administration and were retained there for more than 6 h. They were diffusely
      distributed, primarily in the nerve fiber layer, ganglion cell layer, and
      plexiform layers. Fl-Hsc/Hsp70 was also found in the outer nuclear layer (ONL) at
      6 h after injection. At 24 h post-injection, the proteins were undetectable by
      epifluorescence microscopy of retinal sections, but could still be detected in
      western blots of retinal homogenates. The pattern of protein uptake was similar
      in light-damaged retinas. Ten days after light damage, the retinas in those eyes
      that received injections of Hsc/Hsp70 had greater ONL areas compared to either
      the light-damaged retinas of uninjected eyes or those that had received actin.
      The difference was statistically significant (p<0.05). CONCLUSIONS:
      Intravitreally injected Hsc/Hsp70 is taken up by retinal cells and, when
      administered after an acute injury like light damage, increased the number of
      surviving photoreceptors.

PMID- 11239247
TI  - Protein kinase C alpha and gamma in N/N 1003A rabbit lens epithelial cell
      differentiation.
AB  - PURPOSE: To determine if Protein Kinase C (PKC) plays a role in the initiation of
      lens epithelial cell differentiation into a lens fiber cell. METHODS: PKCalpha or
      PKCgamma was overexpressed in N/N 1003A lens epithelial cells for up to 7 days.
      Phase contrast microscopy was used to observe morphological changes associated
      with PKCalpha or PKCgamma overexpression. Cell cycle changes in cells
      overexpressing PKCalpha or PKCgamma were measured using acridine orange staining
      and flow cytometry. Crystallin levels in cells overexpressing PKCalpha or
      PKCgamma were measured using Western blots and RT-PCR. RESULTS: Significant
      differences in cell cycling were observed between untransfected cells and those
      overexpressing PKCalpha or PKCgamma. Overexpression of PKCalpha and PKCgamma
      caused the cells to lose their epithelial-like appearance and elongate. alphaB
      crystallin expression was detected in all the samples while alphaA-crystallin was
      detected only in cells after 7 days of PKCalpha or PKCgamma overexpression.
      CONCLUSIONS: The observations that alphaA-crystallin is only found in N/N 1003A
      cells overexpressing PKCalpha or PKCgamma for 7 days along with the finding that
      a block in the G0/G1 phase of the cell cycle and the consequent morphological
      changes are observed, indicate that PKCalpha and PKCgamma may have a role in the
      initiation of differentiation in lens epithelial cells.

PMID- 11239248
TI  - Correction: Case 23-2000: Osteomyelitis in HIV-Infected Patients. 

PMID- 11239249
TI  - Factors affecting injury severity to rear-seated occupants in rural motor vehicle
      crashes.
AB  - Injury to rear-seat occupants (RSOs) has received little systematic study in the
      literature. Past studies have focused on patterns of injury presented to the
      emergency department, various aspects of restraint usage and injury, or specific
      populations of RSOs. This is the first systematic analysis of injury severity to
      RSOs. RSOs involved in motor vehicle crashes (MVCs) sustain injuries of equal
      severity as do front-seated occupants (FSOs) involved in the same crash. The
      setting was a rural North Carolina emergency department where patients were
      evaluated at the sole hospital for the county. The design was a 2-year
      retrospective review of all MVCs with RSOs occurring in Pitt County North
      Carolina in calendar years 1988 and 1989. The Wilcoxon Rank-Sum Test and Logistic
      Regression Analysis with Injury Severity Score (ISS) as the dependent variable
      were performed. Three hundred forty-six crashes involving 367 vehicles with RSOs
      and 1,273 occupants that sent 222 patients to the hospital. ISS was higher for
      unrestrained occupants (1.87 versus 0.51), occupants of vehicles driven by
      legally intoxicated drivers (4.04 versus 0.73), occupants between the ages of 30
      and 59 years (1.06 versus 0.65) and FSOs (1.04 versus 0.85) (Wilcoxon Rank-Sum
      test P <.0002). Logistic regression analysis confirmed these findings with the
      exception of more severe injuries for the 30 to 59 age range and impact speed.
      The analysis failed in these 2 cases. Restraint usage offered the greatest
      protective effect (OR 0.37). Lesser protective effects were noted with rear seat
      occupancy (OR 0.43) and age < 13 years (OR 0.77). More severe injuries were
      predicted by driver intoxication (OR 2.5), and age > 60 years (OR 1.25). In our
      rural population, RSOs sustain less severe injuries than FSOs. Restraint usage
      and sober drivers provide a greater protective effect however. Seat location does
      not replace restraint usage or sobriety.

PMID- 11239250
TI  - Hazardous materials events: evaluation of transport to health care facility and
      evacuation decisions.
AB  - The study objective was to analyze hazardous materials event and victim factors
      associated with transportation of victims to a health care facility, and
      evacuation or shelter-in-place of nearby populations. A retrospective review was
      conducted on hazardous materials events in Washington State from 1993 to 1997.
      Bivariate and multiple logistic regression were used to identify risk factors for
      transportation, evacuation, and shelter-in-place. Over five years, 2,654 victims
      from 457 events were reported, with 1,859 (70%) transported to a health care
      facility. Evacuation occurred in 279 (61%) events and shelter-in-place in 14 (3%)
      events. After excluding 14 deaths, regression analysis indicated that victims
      with trauma (OR 5.87, 95% CI 1.41-24.5), thermal burns (6.90, 1.15-41.3),
      dizziness/other CNS symptoms (1.59, 1.00-2.54), and headache (1.54, 1.01-2.35)
      were most likely to be transported. Chemical releases inside buildings (2.09,
      1.06-4.10, compared with transportation events), and involving 3-5 victims (2.86,
      1.54-5.31, compared to 1 victim) or > or =6 victims (8.74, 4.01-19.0), were most
      likely to involve evacuation or shelter-in-place. Events involving sulfuric acid
      (0.15, 0.05-0.49) and sodium hydroxide (0.19, 0.04-0.94) were least likely to
      involve evacuation or shelter-in-place. Prehospital decisions to transport
      victims to a health care facility and evacuate or shelter-in-place nearby
      populations are associated with event and victim factors. Further research is
      needed to determine if these factors also predict need for medical care or
      removal from exposure, and to develop evidence-based prehospital care protocols
      for hazardous materials exposure victims.

PMID- 11239251
TI  - Surveillance for carbon monoxide poisoning using a national media clipping
      service.
AB  - Using a novel method to review carbon monoxide (CO) exposures in the US, the role
      of CO detectors in prevention of CO-related deaths was studied. Using a national
      media clipping service, CO poisonings reported in the US were analyzed. The
      impact of CO detectors was investigated through nonfatal outcomes attributable to
      the presence of CO detectors and case fatality rate comparison among cities with
      and without CO detector ordinances. There were 4,564 CO exposures resulting in
      406 (8.9%) fatalities. Of the exposures 2,617 (57.3%) occurred in the home,
      accounting for 374 (92.1%) deaths. Faulty heating systems constituted 2,540
      (55.6%) exposures and 186 (45.8%) deaths, with alternate heating sources
      responsible for 389 (8.5%) exposures and 104 (25.6%) deaths. Cities with CO
      detector ordinances showed lower case fatality rates as reported in the media
      than those cities without ordinances (P <.001). There were 1,008 (24.2%)
      survivors who attributed their survival to the presence of a CO detector. A media
      clipping service provided insight into CO poisoning demographics. Despite its
      limitations, this tool may calibrate the positive impact of CO detectors on the
      prevention of CO-related deaths.

PMID- 11239252
TI  - Diagnosis of appendicitis in the ED: comparison of surgical and nonsurgical
      residents.
AB  - The purpose of this study was to evaluate the impact of a surgery-based (SB)
      versus nonsurgery-based (NSB) training background of residents on the diagnosis
      of acute appendicitis in the emergency department (ED). The medical records of
      641 adult patients who had undergone an appendectomy during a 3-year period (July
      1996 to June 1999) were reviewed. All the patients were divided into NSB-in
      charge (n = 367) and SB-in charge (n = 274) groups, and demographic and clinical
      data recorded. Both groups' patients showed no differences in either negative
      appendectomy or perforation rates. However, NSB group patients had longer in
      hospital delays in comparison with SB group patients (12.0 +/- 0.7 versus 9.6 +/-
      0.4 hours, P <.05). This longer stay time mainly occurred in the patients with
      negative exploration and uncomplicated appendicitis P <.05). In both groups,
      patients with complicated appendicitis had longer prehospital delay of
      presentation than those with uncomplicated appendicitis. (2.0 +/- 0.2 versus 1.2
      +/- 0.1 days in NSB group; 2.5 +/- 0.5 versus 1.3 +/- 0.2 days in SB group, P
      <.01). The NSB residents tended to order more computed tomography (CT) scans than
      SB residents (12% versus 5.1%, P <.05). With the application of a CT scan, the
      negative appendectomy rate was reduced significantly from 23% to 12%. We
      concluded that under the supervision of board-certified emergency physicians, the
      NSB residents had capabilities similar to SB residents in making correct
      diagnoses of acute appendicitis. In addition, close observation of equivocal
      cases in the ED did not necessarily increase the perforation rate.

PMID- 11239253
TI  - Quality assurance of nurse triage: consistency of results over three years.
AB  - The study objective was to evaluate the capability and the consistency of the
      triage nurse to categorize correctly emergency patients and its impact on the
      waiting time for physician examination over a period of 3 years. The study was
      performed at the emergency department of the Barzilai Medical Center, Ashkelon,
      Israel. A retrospective review of the medical records was performed. All patients
      who were examined by a triage nurse during 2 randomly chosen consecutive weeks
      during the years 1995 and 1998 participated. All the medical records were
      reviewed by the authors and the following information was extracted from the
      medical records: nurse triage category, time of initial evaluation by a triage
      nurse, duration of employment of the nurse in the ED, and her experience as a
      triage nurse, time of initial examination by a physician, the total length of
      stay in the ED, the history taken by the triage nurse and the physician, and the
      physician's urgency category. Patient in urgency category 1 is a patient whose
      condition may deteriorate if not examined within 1 hour; patient in category 2 is
      a patient whose condition may deteriorate if not examined within 2 hours;
      category 3 is all the rest. Any deterioration and or delay of treatment of the
      patients were also recorded. Data concerning patients with an initial complaint
      of chest pain were extracted separately. The data were analyzed using the SPSS
      software and the results were tested by the student t test and chi square test.
      Interobserver agreement was measured using the kappa value. A total of 2,886
      completely full medical records were reviewed by the authors: 1,310 records from
      period I (1995) and 1576 from period II (1998). Of the patients 92% and 88.2%
      were classified by the triage nurse as category 3 in periods I and II
      respectively, 7% and 9.8% as category 2, and 1% and 2% as category 1
      respectively. Full agreement of triage category between nurse and physician was
      found in 90.5% of the cases in period I and 93% in period II (kappa = 0.90 and
      kappa = 0.93 respectively). In period I, 70% of the patients in category 1 were
      examined by a physician in 1 hour versus 100% in period II. Almost all the
      patients in category 2 were examined within 2 hours (98%, 97%), and 98% of those
      in category 3 were examined within 3 hours. The average waiting time for
      physician examination in category 1 patients dropped from 43.1 minutes in period
      I to 18.2 minutes in period II. The average waiting time for the triage nurse was
      9 minutes in period I, and 7.42 minutes in period II. The average length of stay
      in the ED in period I was 1 hour and 24 minutes and 1 hour and 30 minutes in
      period II. Of the anamneses taken by the triage nurse 91.8% were fully identical
      with the physicians' anamneses, but in period II this percentage jumped to 98%.
      Patients with chest pain were categorized correctly by the triage nurse in 76.8%
      of the cases in period I and 72.4% in period II, with an overtriage of 18.6% and
      20.7% respectively (kappa = 0.75, kappa = 0.70 respectively). In our study, nurse
      triage was safe and effective in classifying patients to urgency categories. The
      results are consistent and even improved over a 3-year period. The rates of
      incorrect classification, deterioration, and delay of treatment of patients
      because of incorrect triage are very low. Most of the patients were examined by
      the physician within the expected time. Triage nurse predicted correctly the
      urgency category of patients with chest in most of the cases and the rate of
      missing acute coronary events was very low.

PMID- 11239254
TI  - Coronary artery disease in patients with chest pain who have low-risk clinical
      characteristics and negative cardiac troponin I.
AB  - Patients who have low-risk clinical features and negative cardiac troponin levels
      may be suitable for early discharge after a brief period of observation in the
      emergency department (ED). Little is known about the prevalence and severity of
      coronary artery disease in such patients, although this has implications for
      follow-up. Subjects included 570 patients who were at < or =7% risk of acute
      myocardial infarction (AMI), remained clinically stable (defined as the absence
      of new ischemic changes on their electrocardiograph, signs or symptoms of heart
      failure, the development of a cardiac arrhythmia or hypotension requiring either
      inotropes or volume repletion) and had cardiac troponin I (cTnI) levels <0.2
      microgl(-1) during the initial 12 hours of hospitalization. Clinical features
      were documented and those undergoing stress tests and/or coronary angiograms had
      these graded by 2 independent observers. Overall, 190 (33.3%) of this population,
      who might be considered suitable for early discharge, had objective evidence of
      coronary artery disease. Patients with chest pain who are at low risk of AMI,
      remain clinically stable and have negative cTnI over the initial 12 hours of
      observation are a heterogeneous population, some of who have threatening coronary
      disease. This does not preclude early discharge from the ED but emphasizes the
      need for careful assessment and follow-up.

PMID- 11239255
TI  - Use of the skeletal survey in the evaluation of child maltreatment.
AB  - The radiologic skeletal survey is an important tool for evaluating occult trauma
      in suspected child abuse. The purposes of this study were: (1) to determine the
      incidence of clinically unsuspected fractures detected by skeletal survey, and
      (2) to identify high-risk groups of children who would benefit from skeletal
      surveys. We retrospectively reviewed the medical records of 203 children admitted
      over a 30-month period to Children's National Medical Center for alleged physical
      abuse. Skeletal surveys were ordered based on the treating physicians' clinical
      suspicions. Patients in whom skeletal surveys were positive for an occult
      fracture were studied in more detail. There were 96 skeletal surveys performed;
      of these, 25 were positive for at least 1 clinically unsuspected fracture. Eighty
      percent of occult fractures were found in children younger than 1 year old.
      Presenting with a new fracture or an intracranial injury placed the child at
      higher risk of occult fracture. In contrast, patients with burn injuries had a
      very low yield of occult fractures. The patient's age and type of suspicious
      injury can help guide the physician as to when to obtain a skeletal survey.

PMID- 11239256
TI  - Early revisit, hospitalization, or death among older persons discharged from the
      ED.
AB  - The purpose of this study to determine predictors of revisit, hospital admission,
      or death among older patients discharged from the emergency department (ED). We
      performed a prospective study of patients aged 65 or older in an urban ED. The
      primary outcomes were ED revisit, hospital admission, or death 30 or 90 days
      after discharge from an index ED visit. Of the 463 eligible patients, 75 (16%)
      experienced ED revisit, hospitalization, or death within 30 days, and 125 (27%)
      within 90 days. In multivariate proportional hazards models, physical functioning
      and mental health in the lowest tertile, and lack of supplemental insurance
      predicted revisit, hospitalization, or death within 30 days after ED discharge.
      Poor physical functioning, missing mini-mental state examination, comorbidity,
      and ambulance transport to the initial ED visit predicted 90-day outcome.
      Problems with physical functioning, mental health and supplemental insurance are
      potentially remediable precursors of early morbidity among older patients after
      ED discharge. Future research should examine whether addressing these issues
      among the elderly population will lessen ED return visits, hospitalization, and
      mortality.

PMID- 11239257
TI  - Effectiveness and safety of prehospital urapidil for hypertensive emergencies.
AB  - The objective was to evaluate both the effectiveness and safety of urapidil in
      management of hypertensive emergencies (HE) in the prehospital setting. This was
      an open, prospective study for 6 months. We evaluated systolic (SBP), diastolic
      (DBP), and mean blood pressure (MBP), and heart rate (HR) with continuous
      noninvasive hemodynamic monitoring in 16 consecutive cases of HE. We used
      urapidil at different doses (25 to 100 mg) at 5 minute intervals, according to
      the blood pressure response. The basal DBP was 127 +/- 16 mmHg. Urapidil was
      effective in 15 patients. ANOVA test showed a significant drop out in DBP (P
      <.0001) and HR (P <.004). The highest decrease was obtained in the first 10
      minutes. The decrease in DBP and HR values were significant at 5 minutes versus
      basal (P <.05) and at 10 versus 5 minutes (P <.01). All adverse effects had
      little relevance. Urapidil is effective and safe in management of HE when used by
      a medical team in the prehospital setting.

PMID- 11239258
TI  - The utility of ultrasound to determine ventricular capture in external cardiac
      pacing.
AB  - Determining electrical capture when using an external cardiac pacemaker is often
      difficult and confusing, especially when the resulting clinical signs of an
      effective blood pressure and pulse are inadequate or nondetectable. The objective
      of this study was to determine the efficacy of using 2-dimensional ultrasound
      (US) in determining the presence of ventricular capture of an external cardiac
      pacemaker in a swine model. Five anesthetized swine underwent external cardiac
      pacing (ECP) at variable levels of energy output while concurrent US images and
      electrocardiograph monitoring were recorded on videotape. Determinations of
      capture/no capture were made in the laboratory. Segments of videotape were
      selected to be reviewed by 2 physicians blinded to these laboratory
      determinations of capture and to each other. Kappa levels of agreement were
      determined among the 3 pairs of comparisons. Seventeen segments were reviewed.
      Kappa levels of agreement were 0.76 for Reviewer A versus Laboratory
      determination, 0.88 for Reviewer B versus Laboratory determination, and 0.88 for
      Reviewer A versus Reviewer B. All P values were <.001. These excellent levels of
      agreement show that 2D US in this animal model is highly effective in determining
      the presence of ventricular capture in ECP.

PMID- 11239259
TI  - Prehospital midthigh trauma and traction splint use: recommendations for
      treatment protocols.
AB  - The present study was completed to establish an epidemiologic database defining
      the prehospital occurrence of midthigh trauma/suspected femoral shaft fractures,
      and the use of/need for traction splints (TS) in hope of developing
      recommendations for further treatment protocols. On review of 4,513 paramedic run
      reports for the 12-month period from January 1999 through December 1999, from a
      low-volume urban emergency medical services (EMS) system, 16 persons (0.35% total
      patients) presented with midthigh injuries. Data collected included patient chief
      complaint/injury, mechanism of injury, clinical findings, splint application,
      additional interventions, iatrogenic complications, patient age, and ambulance
      field time. Paramedics noted injuries suspicious for femoral shaft fractures in 5
      patients (31.25% study patients, 0.11% total patients). TSs were applied
      successfully only twice (12.50% study patients, 0.04% total patients). Fourteen
      patients (87.50% study patients) were managed with long backboard immobilization,
      rigid splinting, and/or patient transportation in a position of comfort. No
      sequelae as a result of such care occurred. No inappropriate use, point estimate
      (PE) [(0)/(16) (0.00% to 20.60%)] or unmet need, PE [(0)/(4), 497) (0.00% to
      0.08%)] of care was noted. The data presented in this study suggest that given
      similar EMS system characteristics, prehospital midthigh injuries/suspected
      femoral shaft fractures occur on an extremely rare basis, and treatment with long
      backboard immobilization, rigid splinting, and/or patient transportation in a
      position of comfort may constitute an acceptable course of care. Including TSs as
      essential ambulance equipment may be unnecessary.

PMID- 11239260
TI  - Noninvasive monitoring of oxygen and carbon dioxide.
AB  - Pulse oximetry and capnography are widely used in clinical practice. They provide
      quick and noninvasive methods to estimate arterial oxygen saturation and carbon
      dioxide tension in different situations including emergency departments,
      intensive care units, and during procedures. This article reviews the principles
      of surgery, accuracy, limitations, and clinical applications of these
      instruments.

PMID- 11239261
TI  - The diagnosis and management of orbital blowout fractures: update 2001.
AB  - A cogent update of orbital blowout history, anatomy, and management are included
      with a retrospective study of 59 pure orbital blowout fractures which occurred
      between 1994 and 1998. Our goal is to provide a better understanding of this
      frequently encountered entity and to help augment the confidence of
      nonophthalmologists who will often evaluate patients with suspected orbital
      blowout fractures.

PMID- 11239262
TI  - Cases in electrocardiography.

PMID- 11239263
TI  - Orthopedic pitfalls in the ED: lunate and perilunate injuries.
AB  - Occult dislocations at and around the lunate can accompany wrist trauma. When
      left unrecognized and untreated, these injuries lead to a high incidence of long
      term functional disability and chronic pain. Emergency medicine practitioners
      need to be vigilant for both lunate and perilunate dislocations. This review
      article examines the clinical presentation, diagnostic techniques, and management
      options applicable to the emergency practitioner.

PMID- 11239264
TI  - A comparison of two new devices for emergency airway management: laryngeal tube
      and airway management device.

PMID- 11239265
TI  - Bony prominence pain caused by elevated wheelchair seating pressures.

PMID- 11239266
TI  - Idiopathic dissection of vertebral artery.

PMID- 11239267
TI  - Traumatic intraventricular hemorrhage causing talk and deteriorate syndrome.

PMID- 11239268
TI  - Long-term recurrent infection of tetanus in an elderly patient.

PMID- 11239269
TI  - Millennium bug or electrocardiogram interferences?

PMID- 11239270
TI  - Serious circulatory deficiency during external chest compression for asthma
      attack.

PMID- 11239271
TI  - Vertebral artery dissection and pontine infarct after chiropractic manipulation.

PMID- 11239272
TI  - Inadvertent administration of nebulized acetic acid.

PMID- 11239273
TI  - Lingual tonsillitis: an unusual presentation of mononucleosis.

PMID- 11239274
TI  - Frequency of adverse reactions to prochlorperazine in the ED: a response.

PMID- 11239275
TI  - Acute barium poisoning treated with hemodialysis.

PMID- 11239276
TI  - Intramedullary abscess of the spinal cord.

PMID- 11239278
TI  - Mobility status after inpatient stroke rehabilitation: 1-year follow-up and
      prognostic factors.
AB  - OBJECTIVES: To evaluate the stability of mobility status achieved by stroke
      patients during hospital rehabilitation treatment over time and to identify
      reliable prognostic factors associated with mobility changes. DESIGN: Follow-up
      evaluation in consecutive first-ever stroke patients 1 year after hospital
      discharge. Multiple logistic regressions were used to analyze increases and
      decreases in Rivermead Mobility Index (RMI) scores (dependent variables) between
      discharge and follow-up. Independent variables were medical, demographic, and
      social factors. SETTING: Rehabilitation hospital. PATIENTS: A cohort of 155
      patients with sequelae of first stroke, with a final sample of 141. MAIN OUTCOME
      MEASURES: Mobility status at 1-year follow-up, as measured by the RMI, and odds
      ratios (OR) for improvement and decline in mobility. RESULTS: Functionally, 19.9%
      improved the mobility levels achieved during the inpatient rehabilitation
      treatment; levels of 42.6% worsened. Patients with global aphasia (OR = 5.66; 95%
      confidence interval [CI], 1.50-21.33), unilateral neglect (OR = 3.01; 95% CI,
      1.21-7.50), and age 75 years or older (OR = 5.77; 95% CI, 1.42-23.34) had a
      higher probability of mobility decline than the remaining patients. Postdischarge
      rehabilitation treatment (PDT), received by 52.5% of the final sample, was
      significantly and positively associated with mobility improvement (OR = 5.86; 95%
      CI, 2.02-17.00). Absence of PDT was associated with a decline in mobility (OR =
      3.73; 95% CI, 1.73-8.04). CONCLUSIONS: In most cases, mobility status had not yet
      stabilized at hospital discharge. PDT was useful in preventing a deterioration in
      mobility improvement achieved during inpatient treatment and in helping increase
      the likelihood of further mobility improvement.

PMID- 11239279
TI  - Validity and reliability comparison of 4 mobility measures in patients presenting
      with neurologic impairment.
AB  - OBJECTIVE: To establish the reliability and validity of 4 mobility measures in
      neurologically impaired adults undergoing rehabilitation. DESIGN: Repeated
      assessment of same patients. SETTING: Two specialized neurologic centers in
      England. PATIENTS: Forty-six patients with neurologic disabilities selected from
      inpatient and outpatient rehabilitation centers who were able to stand and walk
      at least 10 meters, with some aid if needed. INTERVENTIONS: Patients were
      assessed twice, at an interval of 7 days, by the same person at the same
      location. Validity and reliability of each measure were compared by means of
      scatterplots, Bland-Altman method, and correlation coefficients. Validity was
      also established by comparing groups of patients expected to differ in mobility.
      MAIN OUTCOME MEASURES: The Rivermead Mobility Index (RMI) standard version and a
      version with 4 levels of answer, the 10-meter timed walk, and the 2-minute walk
      test. RESULTS: The measures showed significant intercorrelation, suggesting that
      all were valid mobility measures. Each was reasonably reliable, with no evidence
      of systematic bias. The revised RMI was less sensitive to differences. The
      distance covered in the 2-minute walk test was significantly decreased for
      patients using aids (p <.0005) and those with impaired leg sensation (p =.02).
      CONCLUSIONS: All 4 measures tested (2 RMI versions, 1-meter timed walk, 2-minute
      walk test) showed similar validity and reliability, and the 4-level RMI version
      failed to show an increased ability to detect differences. All measures showed
      more disability in patients using aids and those with sensory impairment.

PMID- 11239280
TI  - The intra- and interrater reliability of the action research arm test: a
      practical test of upper extremity function in patients with stroke.
AB  - OBJECTIVES: To determine the intra- and interrater reliability of the Action
      Research Arm (ARA) test, to assess its ability to detect a minimal clinically
      important difference (MCID) of 5.7 points, and to identify less reliable test
      items. DESIGN: Intrarater reliability of the sum scores and of individual items
      was assessed by comparing (1) the ratings of the laboratory measurements of 20
      patients with the ratings of the same measurements recorded on videotape by the
      original rater, and (2) the repeated ratings of videotaped measurements by the
      same rater. Interrater reliability was assessed by comparing the ratings of the
      videotaped measurements of 2 raters. The resulting limits of agreement were
      compared with the MCID. PATIENTS: Stratified sample, based on the intake ARA
      score, of 20 chronic stroke patients (median age, 62yr; median time since stroke
      onset, 3.6yr; mean intake ARA score, 29.2). MAIN OUTCOME MEASURES: Spearman's
      rank-order correlation coefficient (Spearman's rho); intraclass correlation
      coefficient (ICC); mean difference and limits of agreement, based on ARA sum
      scores; and weighted kappa, based on individual items. RESULTS: All intra- and
      interrater Spearman's rho and ICC values were higher than .98. The mean
      difference between ratings was highest for the interrater pair (.75; 95%
      confidence interval, .02-1.48), suggesting a small systematic difference between
      raters. Intrarater limits of agreement were -1.66 to 2.26; interrater limits of
      agreement were -2.35 to 3.85. Median weighted kappas exceeded .92. CONCLUSION:
      The high intra- and interrater reliability of the ARA test was confirmed, as was
      its ability to detect a clinically relevant difference of 5.7 points.

PMID- 11239281
TI  - Percutaneous intramuscular neuromuscular electric stimulation for the treatment
      of shoulder subluxation and pain in patients with chronic hemiplegia: a pilot
      study.
AB  - OBJECTIVE: To investigate the feasibility of percutaneous intramuscular
      neuromuscular electric stimulation (perc-NMES) for treating shoulder subluxation
      and pain in patients with chronic hemiplegia. DESIGN: Before-after trial.
      SETTING: University-affiliated tertiary care hospital. PARTICIPANTS: A
      convenience sample of 8 neurologically stable subjects with chronic hemiplegia
      and shoulder subluxation. INTERVENTION: Six weeks of perc-NMES to the subluxated
      shoulder. MAIN OUTCOME MEASURES: Shoulder subluxation (radiograph), shoulder pain
      (Brief Pain Inventory), motor impairment (Fugl-Meyer score), shoulder pain-free
      external rotation (handheld goniometer), and disability (FIM instrument) were
      assessed before treatment (T1), after 6 weeks of neuromuscular stimulation (T2),
      and at 3-month follow-up (T3). A 1-way, repeated-measures analysis of variance
      using the generalized estimating equation approach was used to evaluate
      differences from T1 to T2 and from T1 to T3 for all outcome measures. RESULTS:
      Subluxation (p =.0117), pain (p =.0115), shoulder pain-free external rotation (p
      <.0001), and disability (p =.0044) improved significantly from T1 to T2.
      Subluxation (p =.0066), pain (p =.0136), motor impairment (p <.0001), shoulder
      pain-free external rotation (p =.0234), and disability (p =.0152) improved
      significantly from T1 to T3. CONCLUSIONS: Perc-NMES is feasible for treating
      shoulder dysfunction in hemiplegia and may reduce shoulder subluxation, reduce
      pain, improve range of motion, enhance motor recovery, and reduce disability in
      patients with chronic hemiplegia and shoulder subluxation. Further investigation
      is warranted.

PMID- 11239282
TI  - Reduced hip extension during walking: healthy elderly and fallers versus young
      adults.
AB  - OBJECTIVES: To test the hypothesis that reduced hip extension range during
      walking, representing a limiting impairment of hip tightness, is a consistent
      dynamic finding that (1) occurs with increased age and (2) is exaggerated in
      elderly people who fall. DESIGN: Using a 3-dimensional optoelectronic motion
      analysis system, we compared full sagittal plane kinematic (lower extremity joint
      motion, pelvic motion) data during walking between elderly and young adults and
      between elderly fallers and nonfallers. Comparisons were also performed between
      comfortable and fast walking speeds within each elderly group. SETTING: A gait
      laboratory. PARTICIPANTS: Twenty-three healthy elderly subjects, 16 elderly
      fallers (otherwise healthy elderly subjects with a history of recurrent falls),
      and 30 healthy young adult subjects. MAIN OUTCOME MEASURES: All major peak joint
      angle and pelvic position values. RESULTS: Peak hip extension was the only leg
      joint parameter measured during walking that was both significantly lower in
      elderly nonfallers and fallers than in young adult subjects and was even lower in
      elderly fallers compared with nonfallers (all p <.05). Peak hip extension +/-
      standard deviation during comfortable walking speed averaged 20.4 degrees +/- 4.0
      degrees for young adults, 14.3 degrees +/- 4.4 degrees for elderly nonfallers,
      and 11.1 degrees +/- 4.8 degrees for elderly fallers. Peak hip extension did not
      significantly improve when elderly subjects walked fast. CONCLUSION: An isolated
      and consistent reduction in hip extension during walking in the elderly, which is
      exaggerated in fallers, implies the presence of functionally significant hip
      tightness, which may limit walking performance. Overcoming hip tightness with
      specific stretching exercises is worthy of investigation as a simple intervention
      to improve walking performance and to prevent falls in the elderly.

PMID- 11239283
TI  - Age-related changes in spatial and temporal gait variables.
AB  - OBJECTIVE: To extend recent findings describing the effect of age on spatial and
      temporal gait variables. DESIGN: Experimental. SETTING: A gait analysis
      laboratory. PARTICIPANTS: Two experiments with healthy nonfallers were conducted.
      Experiment 1 included 33 subjects (n = 15, 72.13 +/- 3.96yr; n = 18, 25.06 +/-
      4.02yr); and experiment 2 included 24 subjects (n = 14, 75.57 +/- 6.15yr; n = 10;
      28.10 +/- 3.48yr). INTERVENTIONS: The effect of age, walking velocity, shoe
      condition, and performance of an attention-splitting task on gait variables was
      investigated. MAIN OUTCOME MEASURES: Temporal and spatial gait variables were
      quantified using an instrumented surface across which subjects walked. The
      independent variables were walking velocity variability, stride length
      variability, stride width variability, and stride time variability. RESULTS:
      Stride width variability of older adults was significantly larger than that of
      younger adults in both experiments. The remaining gait variables demonstrated
      nonsystematic or no age-related differences. CONCLUSIONS: With the exception of
      stride width variability, the variability of the remaining gait variables of
      interest were insensitive to the speed at which subjects walked, whether the
      subjects were wearing shoes or not, and performing an attention-splitting task
      while walking. These findings contribute to an emerging interpretive framework
      established by similar work published by others regarding gait variability.

PMID- 11239284
TI  - Comparing stepping-in-place and gait ability in adults with and without
      hemiplegia.
AB  - OBJECTIVE: To determine and compare select temporal-distance measures of stepping
      in-place with gait ability in 2 age-matched groups. DESIGN: Repeated measures,
      matched research design. SETTING: Gait laboratory and hospital outpatient unit.
      PARTICIPANTS: Convenience sample recruited from within the community and the
      outpatient unit of a local rehabilitation hospital included 30 healthy adults
      (age range, 58.1 +/- 10.8yr) and 30 age-matched adults with hemiplegia (age
      range, 58.6 +/- 10.3yr), secondary to a cerebrovascular accident. INTERVENTIONS:
      Subjects were videotaped in the sagittal plane performing stepping-in-place and
      while walking. Select temporal-distance measures obtained by manual calculations
      from the video recordings were determined for 3 20-second trials of each
      activity. MAIN OUTCOME MEASURES: Single limb support duration (SLSD) of the lower
      extremities (LEs) and step frequency during stepping-in-place and during gait.
      RESULTS: A significant difference was found between the step frequency of each
      activity for the adults with hemiplegia (p <.05), but not for the healthy adults.
      A significant difference was also found between SLSD of the same LE across
      activities for each group (p <.05). SLSD of each LE during each individual
      activity, stepping-in-place, or gait, was not significantly different for the
      healthy adults, indicating LE symmetry; but it was significantly different for
      the adults with hemiplegia (p <.05), indicating LE asymmetry. CONCLUSIONS:
      Stepping-in-place incorporates reciprocal, rhythmic LE movement patterns similar
      to gait. And, although SLSD of the LEs was different between the activities in
      both groups, each group showed similar LE movement patterns during each
      individual activity. In addition, step frequency was consistent between the
      activities for the healthy adults. These results seem to indicate that the
      reciprocal, rhythmic LE movement patterns, which are invoked during gait, may
      also be invoked during stepping-in-place. However, further research is needed to
      enhance the data related to stepping-in-place and gait ability in clinical
      populations.

PMID- 11239285
TI  - Temporal stride and force analysis of cane-assisted gait in people with
      hemiplegic stroke.
AB  - OBJECTIVE: To understand the underlying biomechanics of temporal stride and force
      in people with hemiplegic stroke during cane-assisted walking. DESIGN: Three
      forceplates, 6 cameras, and an instrumented cane were integrated to analyze the
      cane-assisted gait of people with hemiplegic stroke. Temporal-stride parameters,
      and peak vertical, anterior (propulsive), posterior (braking), and lateral shear
      forces, as well as propulsive-breaking impulses were analyzed. SETTING: Chang
      Gung Memorial Hospital, Medical Center, Taiwan. PARTICIPANTS: Twenty people with
      hemiplegic stroke. MAIN OUTCOME MEASURES: Temporal-stride and force parameters.
      RESULTS: All patients walked at a relatively slow speed, ranging from 4.2 to
      35.8cm/s. The triple and double support occupied most of the gait cycle (GC),
      whereas the single support occupied only 10% of GC. The applied vertical,
      propulsive, braking, and lateral shear forces on either foot and the cane were
      89.7% to 97.6%, 2.2% to 4.8%, 2.9% to 3.9%, and 5.5% to 6.7% body weight (BW),
      respectively. Patients applied less than 25% BW of peak vertical forces on the
      cane. They applied greater peak propulsive forces and impulses on the sound foot,
      while applying greater peak braking forces and impulses on the affected foot and
      cane. CONCLUSIONS: The cane provided support and a braking function for people
      with hemiplegic stroke. People with stroke walking with cane assistance rely
      mostly on the sound limb for propulsion, while using the affected limb and cane
      for braking. Data provided could be useful in assessing the nature of cane
      assistance and in planning therapeutic strategies for people with stroke.

PMID- 11239286
TI  - Levels of self-awareness after acute brain injury: how patients' and
      rehabilitation specialists' perceptions compare.
AB  - OBJECTIVE: To examine self-awareness regarding performance on 4 daily living
      tasks and to test theoretical predictions for a model of self-awareness in
      persons with acquired brain injury. DESIGN: A comparative design examining the
      level of self-awareness recorded by patients and actual patient performance as
      judged by rehabilitation clinicians. SETTING: A community-based residential
      center providing comprehensive rehabilitation services to persons with acquired
      brain injury. PARTICIPANTS: Fifty-five persons with acquired brain injury and the
      identified potential to return to independent function in the community. Ten
      subjects without brain injury provided comparison data. INTERVENTION: Information
      was collected by using patient self-report, clinician rating of patient
      performance, patient rating of non-brain-injured subjects, and clinician rating
      of non-brain-injured subjects. MAIN OUTCOME MEASURES: Three self-awareness
      criteria were examined: intellectual, emergent, and anticipatory. Self-awareness
      was rated for 3 tasks: dressing, meal planning, and money management. RESULTS:
      Statistically significant differences (p <.05) were found for all levels of self
      awareness across the 3 tasks. Persons with brain injury judged their abilities
      higher than clinician ratings of actual performance. No statistical support was
      found for a hierarchy among intellectual, emergent, and anticipatory self
      awareness. CONCLUSIONS: No evidence was found supporting a hierarchy among levels
      of self-awareness as defined and measured in the present study. New methods for
      operationally defining intellectual, emergent, and anticipatory self-awareness
      are necessary to examine the relationship between self-awareness and performance.

PMID- 11239287
TI  - Long-latency auditory-evoked potentials in severe traumatic brain injury.
AB  - OBJECTIVE: To detect the effects of different deviant stimuli on long-latency
      auditory-evoked potentials (LLAEPs) in patients with severe impairment of
      consciousness from traumatic brain injury (TBI) and to define their prognostic
      value for late functional outcome. DESIGN: Correlational study on a prospective
      cohort. SETTING: Brain injury rehabilitation center. PATIENTS: Eleven volunteers
      and 21 consecutively sampled patients with severe TBI referred to the inpatient
      intensive rehabilitation unit of primary care in a university-based system. MAIN
      OUTCOME MEASURES: The LLAEPs recorded with different paradigms; and the Glasgow
      Outcome Scale (GOS), Disability Rating Scale (DRS), FIMtrade mark instrument, and
      Neurobehavioural Rating Scale (NBHRS). RESULTS: N100-P150 complex showed high
      reliability. Patients with good outcomes showed N100 and P150 mean latencies
      similar to those of unimpaired patients and shorter than patients with
      unfavorable outcomes. When the deviant stimulus was the patient's name, N100
      latency showed high correlations with DRS (p <.007), FIM (p <.01), and NBHRS (p
      <.009). P250 and P300 showed a low percentage of occurrence with passive
      paradigms in both patients and controls. Their scores were inversely correlated
      to the Glasgow Coma Scale (p <.03) and the Innsbruck Coma Scale (p <.003), but no
      significant correlations were found with functional and behavioral outcomes.
      Patients with GOS score 1-2 1 year posttrauma had significantly longer latency
      and lower amplitude of N100 and P150 than those with GOS score 4-5. CONCLUSIONS:
      LLAEPs can be recorded in patients with severe impairment of consciousness by
      means of passive paradigms. The use of a stimulus that is relevant for the
      patient can enhance the accuracy of the test and its relationship with functional
      outcome.

PMID- 11239288
TI  - Dynamic water exercise in individuals with late poliomyelitis.
AB  - OBJECTIVE: To evaluate the specific effects of general dynamic water exercise in
      individuals with late effects of poliomyelitis. DESIGN: Before-after tests.
      SETTING: A university hospital department. PARTICIPANTS: Twenty-eight individuals
      with late effects of polio, 15 assigned to the training group (TG) and 13 to the
      control group (CG). INTERVENTION: The TG completed a 40-minute general fitness
      training session in warm water twice weekly. Assessment instruments included the
      bicycle ergometer test, isokinetic muscle strength, a 30-meter walk indoors, Berg
      balance scale, a pain drawing, a visual analog scale, the Physical Activity Scale
      for the Elderly, and the Nottingham Health Profile (NHP). MAIN OUTCOME MEASURES:
      Peak load, peak work load, peak oxygen uptake, peak heart rate (HR), muscle
      function in knee extensors and flexors, and pain dimension of the NHP. RESULTS:
      The average training period was 5 months; compliance was 75% (range, 55-98). No
      negative effects were seen. The exercise did not influence the peak work load,
      peak oxygen uptake, or muscle function in knee extensors compared with the
      controls. However, a decreased HR at the same individual work load was seen, as
      well as a significantly lower distress in the dimension pain of the NHP.
      Qualitative aspects such as increased well-being, pain relief, and increased
      physical fitness were reported. CONCLUSIONS: A program of nonswimming dynamic
      exercises in heated water has a positive impact on individuals with late effects
      of polio, with a decreased HR at exercise, less pain, and a subjective positive
      experience. The program was well tolerated (no adverse effects were reported) and
      can be recommended for this group of individuals.

PMID- 11239289
TI  - Preoperative expectations and postoperative quality of life in liver transplant
      survivors.
AB  - OBJECTIVE: To assess normalization in the lives of liver transplant patients and
      the impact of preoperative expectations on postoperative quality of life (QOL).
      DESIGN: A semistructured interview, 2 QOL questionnaires, and chart reviews of
      medical histories. SETTING: Internal medicine department at Innsbruck university
      hospital, Austria. PARTICIPANTS: Fifty-five patients (32 men, 23 women) with
      liver transplants. INTERVENTIONS: The Sickness Impact Profile (SIP) and
      Functional Assessment of Cancer Therapy-General. RESULTS: Patients' preoperative
      expectations of a normal life style posttransplantation were predominantly
      optimistic (60%), but postoperatively only 40% thought that their expectations
      had been realized. The patients' SIP values showed significant impairments in
      nearly every area of life when compared with the values of a healthy control
      group. Only "complications during the hospitalized phase" had a statistically
      significant impact among the sociodemographic and clinical parameters on
      postoperative QOL. The lowest QOL scores were found among patients whose
      expectations of a return to normal life style had not been realized. CONCLUSION:
      Unmet life-style expectations after liver transplantation may lead to increased
      stress, which affects QOL long term. This finding is of clinical relevance;
      therapeutic measures, particularly professional pretransplant counseling, are
      indicated.

PMID- 11239290
TI  - Postural control in the elderly: an analysis of test-retest and interrater
      reliability of the COP-COM variable.
AB  - OBJECTIVES: To estimate the test-retest and interrater reliability of the center
      of pressure-center of mass (COP-COM) variable of postural control in the elderly.
      DESIGN: The biomechanic variable COP-COM, which represents the distance between
      the COP and the COM, was determined from 2 AMTI force platforms and 3 OPTOTRAK
      position sensors. Measurements were taken in quiet position, double leg stance,
      and eyes open and eyes closed conditions. SETTING: Laboratory environment.
      PARTICIPANTS: Forty-five healthy subjects, 8 patients with diabetes neuropathy,
      and 7 stroke survivors, all of whom were at least 60 years old. INTERVENTIONS:
      Subjects were evaluated on 2 separate occasions within 7 days by the same
      evaluator to determine test-retest reliability. Interrater reliability was
      determined the same day. MAIN OUTCOME MEASURES: The biomechanic variable COP-COM,
      which represents the distance between the COP and the COM in terms of root mean
      square. The mean of 4 trials of the COP-COM variable for each condition was used
      for statistical analysis. Intraclass correlation coefficients (ICCs) were used.
      RESULTS: The COP-COM variable has good reliability for both the test-retest and
      interrater studies, but its reliability varies according to the direction of the
      COP-COM. For the test-retest and interrater studies, the ICC ranged from.89 to.93
      in the anteroposterior direction and from.74 to.79 in the mediolateral direction.
      CONCLUSION: The equivalence of the test-retest and interrater coefficients
      obtained suggests that the measurement error of the COP-COM variable is mainly
      linked to the biologic variability of this measure over a short period of time.
      Using the mean of 4 trials stabilizes the COP-COM variable enough to be
      potentially used to evaluate clinical change.

PMID- 11239291
TI  - Three-point gait crutch walking: variability in ground reaction force during
      weight bearing.
AB  - OBJECTIVE: To investigate variability in ground reaction force (GRF) and
      kinematics on both sides during 3-point partial weight-bearing (PWB) crutch
      walking. DESIGN: Within-subject comparisons of kinematic and kinetic data
      collected at different levels of 3-point crutch walking: 10%, 50%, and 90% PWB at
      comfortable speeds. SETTING: An applied biomechanics lab in a university setting.
      An applied biomechanics lab in a university setting. PARTICIPANTS: Twelve healthy
      college students (9 women, 3 men). MAIN OUTCOME MEASURES: Spatial and temporal
      variables, major peak kinematic data, and peak GRFs from force platforms during
      the gait cycle. RESULTS: Large variations were found in replicating the target
      levels of PWB, particularly at 10% and 90% PWB. Subjects had a shorter stance
      phase and longer swing phase during the crutch walking gait cycle. Velocity
      significantly decreased (p =.006) because of decreased cadence (p =.002).
      Slightly greater hip abduction and external rotation on the noninvolved side and
      slightly less hip adduction and internal rotation on the involved side indicated
      that the center of gravity shifted slightly from the involved side toward the
      noninvolved side. There was no increase in vertical GRF, and there was a
      relatively constant loading pattern on the noninvolved side. CONCLUSIONS:
      Subjects have difficulty replicating a prescribed weight-bearing restriction. A
      shift of the center of gravity toward the noninvolved side may reduce the weight
      distribution on the involved side.

PMID- 11239292
TI  - Gonadectomy and reduced physical activity: effects on skeletal muscle.
AB  - OBJECTIVES: To examine the effects of testosterone (TST) loss on skeletal muscle
      contractile function and the potential interactive effects of TST loss and
      physical inactivity. DESIGN: Randomized control trial. ANIMALS: Forty-eight male
      rats (age, 6mo) were placed into control (Con) or gonadectomized (Orx) groups.
      INTERVENTION: Two weeks after Orx or sham surgery, half the Con and Orx rats were
      hind-limb unloaded (HLU) to reduce muscle activity for 2 weeks. Subsequently, in
      situ contractile function tests were performed on the soleus (SOL), plantaris
      (PLAN), peroneus longus (PER), and extensor digitorum longus (EDL). These 4
      muscles and gastrocnemius (GAST) then were removed, weighed, sectioned, and
      stained with adenosine triphosphatase for fiber typing and fiber area measures.
      MAIN OUTCOME MEASURES: Peak tetanic tension (P(0)), time to peak twitch
      contraction (TPT), half relaxation time (RT(1/2)), muscle mass, fiber area, and
      specific tension (ratio of P(0)/muscle mass). RESULTS: Body weight and muscle
      mass were similar in the Con and Orx groups. The ratio of P(0) to muscle mass was
      significantly (p <.05) reduced with Orx in SOL (20%), PLAN (18%), PER (28%), and
      EDL (20%). TPT and RT(1/2) were significantly faster after Orx in PLAN, PER, and
      EDL. HLU significantly reduced muscle mass in SOL, PLAN, and GAST in Orx and
      intact groups. HLU also caused a significant decline in SOL and PLAN P(0). The
      loss in P(0) in the Orx-HLU rats was no greater than the decline in P(0) with HLU
      alone. CONCLUSIONS: Gonadectomy results in a loss of P(0) regardless of muscle
      fiber type or function, it is likely to speed up TPT and RT(1/2), and it does not
      exacerbate HLU-related atrophy and P(0) loss. Findings may have implications for
      men with reduced TST levels, as in aging, for instance.

PMID- 11239293
TI  - Wheelchair use by patients with amyotrophic lateral sclerosis: a survey of user
      characteristics and selection preferences.
AB  - OBJECTIVES: To determine wheelchair types and features that are most beneficial
      to patients with amyotrophic lateral sclerosis (ALS), to ascertain at what stage
      of disease and disability patients benefit from wheelchair use, and to pinpoint
      the differences in patient characteristics between the users of manual and
      motorized wheelchairs. DESIGN: Internally generated questionnaire. SETTING: A
      neuromuscular clinic. PATIENTS: Forty-two patients (28 men, 14 women) with ALS
      who used wheelchairs and whose mean age was 53.9 years (range, 32-75yr). MAIN
      OUTCOME MEASURE: Wheelchair users completed a 39-item survey. RESULTS: At the
      time of the survey, the patients' mean Appel ALS rating scale total score was
      84.5 (range, 48-138), indicating moderate disability. Forty-one patients reported
      that wheelchairs permitted them greater interaction in their communities; 33 were
      "very satisfied" with the positive impact of wheelchair use on their activity
      levels. Most users did not work and needed caregiver assistance for activities of
      daily living. The most desirable wheelchair features provide extra comfort
      (supports for the head, neck, trunk, extremities) and have improved
      maneuverability (lightweight frame, smaller wheelbase). Undesirable features are
      low sling backs and sling seats, nonremovable static leg rests, and large frames.
      No significant differences were reported between manual wheelchair users and
      motorized wheelchair users in terms of overall disease symptom severity, arm and
      leg strength, and bulbar function. However, motorized wheelchairs offer patients
      a greater sense of independence and an improved sense of well-being. CONCLUSION:
      Information obtained directly from wheelchair users with ALS provided first-hand
      experience concerning the most and least desirable features of wheelchairs and
      may help other ALS patients make informed decisions when purchasing a wheelchair.

PMID- 11239294
TI  - Use of sonography and radioisotope renography to diagnose hydronephrosis in
      patients with spinal cord injury.
AB  - OBJECTIVE: To study the accuracy of sonography and radioisotope renography in
      detecting hydronephrosis in patients with spinal cord injury (SCI). DESIGN:
      Prospective, blinded comparison study. SETTING: Rehabilitation hospital
      affiliated with a medical college. PARTICIPANTS: One hundred and nine patients
      with SCI (21 women, 88 men) participated. INTERVENTIONS: Comprehensive urologic
      examinations including clinical evaluation, laboratory tests, intravenous
      urography (IVU), sonography, radioisotope renography (renal scan), voiding
      cystourethrography, and cystometry. The findings at sonography and renal scan
      were separately compared with the final diagnosis interpreted by IVU and clinical
      findings. MAIN OUTCOME MEASURES: Effective renal plasma flow, pyelocaliectasis,
      and positive and negative predictive value. RESULTS: A total of 235 kidneys were
      analyzed. Sonography correctly excluded the presence of hydronephrosis in 173 of
      192 nonobstructed kidneys. Sonograms were interpreted as positive in 41 of 43
      kidneys with documented hydronephrosis. Renal scan correctly excluded 161
      nonobstructed kidneys. The renal scan detected 39 of 43 kidneys with
      hydronephrosis. The sensitivity of sonography was.96 with a specificity of.90.
      Renal scan reached a sensitivity of.91 with a specificity of.84. CONCLUSION:
      Sonography and renal scan are safe, sensitive, and specific for detecting
      hydronephrosis. Combined use of both methods appears to be a reliable alternative
      to IVU in the long-term follow-up for patients with SCI with neurogenic bladder
      dysfunction.

PMID- 11239295
TI  - An exploratory study of pressure ulcers after spinal cord injury: relationship to
      protective behaviors and risk factors.
AB  - OBJECTIVES: To identify protective behaviors and risk factors associated with the
      development of pressure ulcers (PUs) after spinal cord injury (SCI). DESIGN: A
      cross-sectional study to evaluate the relationship between protective behaviors
      and risk factors and 3 PU outcomes: a current PU, PUs within the past year, and
      ever hospitalized for a PU. Logistic regression was then used to identify the
      variables most strongly associated with PU outcomes. SETTING: Data were collected
      by case managers employed by the Arkansas Spinal Cord Commission, an agency that
      provides services to persons with SCI. PARTICIPANTS: A total of 650 of 991
      eligible individuals with SCI from a statewide population-based SCI registry
      participated. All ambulatory participants were eliminated, leaving 560 patients.
      Average age of the respondents was 27.2 years at injury (median age, 25yr) and
      43.6 years at the time of the survey (median age, 42yr). MAIN OUTCOME MEASURES: A
      200-item interview was developed to measure a broad range of outcomes associated
      with SCI (including secondary conditions such as PUs), as well as risk and
      protective behaviors related to these outcomes. RESULTS: Several characteristics
      and behaviors were related to PU outcomes. Being underweight (odds ratio [OR] =
      2.18), having used medications to treat pain (OR = 1.33) or spasticity (OR =
      1.31), having smoked at least 100 cigarettes over a lifetime (OR = 1.31), and
      being a current smoker (OR = 1.21) were associated with having a PU in the past
      year. Having completed a college degree (OR = 0.23), being married (OR = 0.49),
      and being currently employed (OR = 0.54) were associated with a lower risk of
      having a PU in the past year. Being underweight (OR = 1.94), having a history of
      incarceration (OR = 1.78), having attempted suicide (OR = 1.71), and reporting
      alcohol or drug treatment (OR = 1.65) were associated with having been
      hospitalized for a PU since injury. This study was unable to evaluate the
      efficacy of traditional health maintenance or protective behaviors for PUs, such
      as weight shifts or skin checks. CONCLUSIONS: PUs are least likely to occur among
      individuals who maintain normal weight, return to a work and family role, and who
      do not have a history of tobacco use, suicidal behaviors, or self-reported
      incarcerations, or alcohol or drug abuse. Additional research is needed to
      identify better the risk factors for the occurrence of PUs.

PMID- 11239296
TI  - Predicting "charge outliers" after spinal cord injury: a multicenter analysis of
      demographics, injury characteristics, outcomes, and rehabilitation charges.
AB  - OBJECTIVE: To describe the distribution of charges, to distinguish between
      "charge outliers" and nonoutliers, and to identify a model that uses demographics
      and injury characteristics to predict charge outlier status in individuals with
      spinal cord injury (SCI). DESIGN: Retrospective data analysis of patients
      admitted to 24 acute inpatient rehabilitation national Spinal Cord Injury Model
      Systems centers. Statistical analysis, including proportions, means, and standard
      deviations (SDs), were compiled for the following variables: demographic and
      injury information, rehabilitation charges, medical complications, associated
      injuries, and surgical procedures. SETTING: Tertiary, university medical centers
      participating in the National Institute on Disability and Rehabilitation
      Research's SCI Model Systems project. PARTICIPANTS: A total of 13,392 patients
      who were admitted to 24 acute, intensive, interdisciplinary rehabilitation
      settings after traumatic SCI between November 1972 and August 1996. MAIN OUTCOME
      MEASURES: Statistical data analysis was used to determine significance between
      charge outliers and nonoutliers on the basis of demographic, injury
      characteristics, and clinical factors. Outliers, under the current diagnostic
      related group system, are defined as cases in which lengths of stay exceed the
      mean by the lesser of 20 days or 1.94 SDs. RESULTS: Statistically significant
      differences were found between SCI charge outliers and nonoutliers based on
      ethnicity, education, employment, level of injury, American Spinal Injury
      Association impairment classification, and sponsor of hospitalization. On
      average, outliers were 4 years older than nonoutliers, and tended to have more
      associated injuries, pressure ulcers, surgical procedures, and medical
      complications. A forward-conditional stepwise multiple logistic regression
      analysis was used to confirm univariate analysis and to predict the presence or
      absence of outliers based on the predictor variables. A model for the prediction
      of SCI charge outlier status was defined. CONCLUSIONS: SCI charge outliers are
      most likely to be retired, insured, have high cervical level injuries, and be
      educated beyond high school. Improved treatment efficiency serves as a means of
      cost reduction and is a reason to identify outlier characteristics.

PMID- 11239298
TI  - Supine fall in lung volumes in the assessment of diaphragmatic weakness in
      neuromuscular disorders.
AB  - OBJECTIVE: To determine whether diaphragmatic function can be determined by
      noninvasive respiratory indices in neuromuscular disease. DESIGN: Vital capacity
      (VC) and mouth pressure generated during a maximal static inspiratory effort (Pi
      max) were measured with patients in both sitting and supine positions. SETTING:
      Rehabilitation hospital. PATIENTS: Twenty-four patients with generalized
      neuromuscular disease. MAIN OUTCOME MEASURES: Changes in indices from sitting to
      supine position were compared with invasive diaphragmatic function indices
      consisting of transdiaphragmatic pressures during maximal sniff (Pdi sniff) and
      the ratio of gastric pressure (Pga) increases over transdiaphragmatic pressure
      (DeltaPga/DeltaPdi) during quiet breathing. RESULTS: The fall in VC in the supine
      position was greater in the 15 patients who had spontaneous paradoxical
      diaphragmatic motion (DeltaPga/DeltaPdi < 0) than in the 9 patients who did not.
      Specificity and sensitivity of a greater than 25% supine fall in VC for the
      diagnosis of diaphragmatic weakness (DeltaPga/DeltaPdi < 0 and/or Pdi sniff <
      30cmH2O) were 90% and 79%, respectively. Stepwise multiple regression analysis of
      Pdi sniff showed that both the supine fall in VC and Pi max were associated with
      diaphragmatic weakness (R(2) =.66; p <.0001). These factors contributed 52% and
      14% of the Pdi sniff variance, respectively. CONCLUSIONS: Simple VC measurement
      in the sitting and supine positions may be helpful in detecting severe or
      predominant diaphragmatic weakness.

PMID- 11239297
TI  - Stability of the lumbar spine after intradiscal electrothermal therapy.
AB  - OBJECTIVE: To assess the stability of the human lumbar cadaveric spinal motion
      segment before and after treatment with intradiscal electrothermal therapy
      (IDET). DESIGN: An in vitro biomechanic analysis of 5 human cadaveric spinal
      motion segments by using nondestructive biomechanic testing in flexion/extension,
      lateral bending, and axial rotation with loads of 0N, 600N, and 1200N. SETTING:
      University-based hospital research center. CADAVERS: Spinal unit specimens (upper
      and middle lumbar) from 5 human cadavers (age range, 39-79yr). INTERVENTIONS: A
      spinal catheter consisting of a thermal-resistive heating coil was placed
      circumferentially into the outer annulus by using the standard extrapedicular
      discographic technique through a 17-gauge introducer needle. The disc was then
      heated in a saline bath (37 degrees C) from 65 degrees C up to 90 degrees C for a
      total of 17 minutes. MAIN OUTCOME MEASURE: The stability of the spinal segments
      was measured before and shortly after IDET. Stability of the spine was measured
      as the compliance of the spine (the angular deformation afforded by the spine
      under applied bending moments). RESULTS: With increasing preloads, there is a
      decrease in motion of the spinal segment in all planes of testing. However, there
      was no significant difference (p >.05) in the stability of the lumbar spine
      before and after treatment with IDET. CONCLUSIONS: IDET does not destabilize the
      spinal motion segment in vitro.

PMID- 11239299
TI  - Inpatient interdisciplinary rehabilitation after total hip arthroplasty surgery:
      a comparison of revision and primary total hip arthroplasty.
AB  - OBJECTIVES: To describe outcomes of revision total hip arthroplasty (THA)
      patients who underwent interdisciplinary inpatient rehabilitation, and to compare
      them with primary THA patients. DESIGN: Descriptive and case-control study.
      SETTING: Forty-bed, community-based, freestanding rehabilitation hospital.
      PATIENTS: Thirty-nine revision THA subjects, gender- and age-matched with 39
      primary THA controls. INTERVENTION: Inpatient interdisciplinary rehabilitation.
      MAIN OUTCOME MEASURES: FIM instrument, length of stay, hospital charges, and
      disposition location. RESULTS: The average revision THA patient stayed 10.5 days,
      improved from an admission FIM score of 89 to a discharge FIM score of 110, and
      incurred a hospital charge of $10,600. Of the revision THA patients, 98% were
      discharged home, and orthopedic-related complications were uncommon. No
      significant differences existed between revision and primary THA patients in any
      outcome measures. A trend toward higher rehabilitation charges ($12,400 vs $9500,
      p =.07) was found in revision THA patients who wore a hip orthosis. Otherwise, no
      differences were found in outcome measures based on the type of revision surgery,
      the presence of weight-bearing restrictions, or the presence of orthopedic
      complications. CONCLUSIONS: THA patients selected for inpatient rehabilitation
      have favorable short-term functional outcomes. The type of THA (primary vs
      revision) is not an independent differentiating factor.

PMID- 11239300
TI  - Diagnosis and management of urinary incontinence in the older patient.
AB  - OBJECTIVES: To review the various causes of urinary incontinence (UI) in elderly
      patients and to outline a therapeutic approach to the clinical management of UI.
      DATA SOURCES: Online search of MEDLINE and additional references selected from
      the articles found during the search. STUDY SELECTION: All peer-reviewed articles
      and review articles listed on MEDLINE published between 1966 and 1999. Key search
      terms included urinary incontinence, geriatric, aging, pelvic floor
      rehabilitation, and indwelling catheter. DATA EXTRACTION: Articles with clinical
      relevance to the geriatric population were selected based on the robustness of
      the studies and reviews. If applicable, data from studies of healthier or younger
      populations was extrapolated to the elderly population examined in this review.
      DATA SYNTHESIS: UI is a common occurrence among older adults treated in
      rehabilitation settings. The causes of UI in the elderly vary, including
      transient causes, established pathologic states of the urinary tract, and
      systemic multifactorial influences. Both behavioral and pharmacologic management
      strategies can successfully be implemented for UI, even in the frail elderly.
      CONCLUSION: UI can be effectively investigated and treated by rehabilitation
      practitioners by following a simple, stepwise approach.

PMID- 11239302
TI  - ACRM: rebirth and renewal.

PMID- 11239301
TI  - Effects of bromocriptine in a patient with crossed nonfluent aphasia: a case
      report.
AB  - OBJECTIVE: Because studies have shown some positive effects of the dopaminergic
      agent bromocriptine for improving verbal production in patients with nonfluent
      aphasia, we examined its effect in a patient with an atypical form of crossed
      nonfluent aphasia from a right hemisphere lesion. DESIGN: Open-label single
      subject experimental ABAB withdrawal design. PATIENT: A right-handed man who,
      after a right frontal stroke, developed nonfluent aphasia, emotional aprosodia,
      and limb apraxia. INTERVENTION: Escalating doses up to 20mg of bromocriptine in 2
      separate phases. MAIN OUTCOME MEASURES: We measured verbal fluency (words/min in
      discourse, Thurstone letter fluency), expression of emotional prosody, and
      gesture production. RESULTS: The patient showed substantial improvement in both
      verbal fluency measures and no significant improvement in gesture or emotional
      prosody. Verbal fluency improvements continued in withdrawal phases. CONCLUSIONS:
      Our results are less likely caused by practice or spontaneous recovery because we
      observed little improvement in emotional prosody and gesture tasks. Verbal
      fluency improvements during treatment and withdrawal phases suggest that the
      effects of bromocriptine may be long-lasting in its influence on the neural
      networks subserving verbal initiation.

PMID- 11239303
TI  - The John Stanley Coulter lecture. The power of compassion and caring in
      rehabilitation healing.
AB  - Rehabilitation of persons with catastrophic illnesses or injuries is a complex,
      labor-intensive interaction between patients and caregivers. Experiences of
      overwhelming loss and suffering evoke strong emotions that shape the behavior of
      both patients and staff during the rehabilitation process. In response to each
      patient's unique experience, compassion, caring, and other humanistic qualities
      of the effective caregiver help create a healing environment. Although these
      qualities are universally accepted as important, they have not been widely
      studied or critically examined. In recent years, however, there has been a
      growing interest in use of scientific methods to investigate the impact of
      "humanistic elements" (ie, complementary and alternative medicine) as therapeutic
      agents. A review of 7 articles from this literature provides examples of research
      based interventions with potential for enhancing outcomes in traditional
      rehabilitation populations. In today's high-tech impersonal health care system,
      the use of scientific methods to show that humanistic treatments are effective
      may represent an important new frontier and opportunity for rehabilitation
      research.

PMID- 11239304
TI  - Continuously infused intrathecal baclofen over 12 months for spastic hypertonia
      in adolescents and adults with cerebral palsy.
AB  - OBJECTIVE: To determine if the continuous intrathecal delivery of baclofen will
      control spastic hypertonia caused by long-standing cerebral palsy (CP). DESIGN:
      Case series. SETTING: Tertiary care outpatient and inpatient rehabilitation
      center directly attached to a university hospital. PATIENTS: Thirteen CP patients
      (average age, 25yr; range, 13--43yr) with intractable spastic hypertonia and
      quadriparesis (one of whom had predominate diplegia) who had not responded to
      oral medications including baclofen. INTERVENTION: Patients were screened via a
      bolus injection of baclofen intrathecally. Those who dropped an average of 2
      points on their lower extremity (LE) Ashworth scores were offered computer
      controlled pump implantation for 12 months of continuous delivery of intrathecal
      baclofen (ITB). MAIN OUTCOME MEASURES: Ashworth rigidity scores, spasm scores,
      and deep tendon reflex scores were collected for both the upper extremities (UEs)
      and LEs. Differences over time were assessed via descriptive statistics and
      Wilcoxon's signed-rank test. RESULTS: After 1 year of continuous ITB treatment,
      the average LE Ashworth score +/- standard deviation decreased from 3.4 +/- 1.2
      to 1.5 +/- 0.7 (p <.0001), spasm score from 1.4 +/- 1.6 to 0.6 +/- 1.2 (p
      =.1024), and reflex score from 2.5 +/- 1.2 to 0.7 +/- 1.1 (p <.0001). The average
      UE Ashworth score decreased from 3.0 +/- 1.2 to 1.7 +/- 1.0 (p <.0001), spasm
      score from 1.2 +/- 1.6 to 0.2 +/- 0.6 (p =.0135), and reflex score from 2.3 +/-
      0.7 to 0.5 +/- 0.9 (p <.0001). The average ITB dose required to attain these
      effects at 1 year was 263 +/- 91microg continuously infused per day. CONCLUSION:
      Continuously infused ITB can reduce spastic hypertonia in the UEs and LEs
      associated with long-standing CP. This reduction in tone will allow more freedom
      of movement and the potential for improved function.

PMID- 11239305
TI  - Functional magnetic stimulation for conditioning of expiratory muscles in
      patients with spinal cord injury.
AB  - OBJECTIVE: To evaluate the effectiveness of functional magnetic stimulation (FMS)
      in conditioning expiratory muscles patients with spinal cord injury (SCI).
      DESIGN: A prospective before-after trial. SETTING: The Functional Magnetic
      Stimulation Laboratory of the SCI Health Care Group, VA Long Beach Health Care
      System, and the Spinal Cord Injury Services, Department of Veterans Affairs, Palo
      Alto Health Care System. PARTICIPANTS: Eight men with tetraplegia. INTERVENTION:
      Expiratory muscle training was achieved by placing a magnetic stimulator with a
      round magnetic coil along subjects' lower thoracic spine. MAIN OUTCOME MEASURES:
      Measures taken were the maximal expired pressure at total lung capacity (MEP-TLC)
      and at functional residual capacity (MEP-FRC), expiratory reserve volume (ERV),
      and the forced expiratory flow rate at TLC (FEF-TLC) and at FRC (FEF-FRC) by
      subjects' voluntary maximal efforts. RESULTS: After 4 weeks of conditioning, the
      mean +/- standard error of the mean values were: MEP-TLC, 55.3 +/- 8.6cmH(2)O;
      MEP-FRC, 29.6 +/- 5.6cmH(2)O; ERV,.57 +/-.08L; FEF-TLC, 4.3 +/- 0.5L/s; and FEF
      FRC, 1.9 +/- 0.2L/s. These values correspond to, respectively, 129%, 137%, 162%,
      109%, and 127% of pre-FMS conditioning values. When FMS was discontinued for 2
      weeks, the MEP-TLC returned to its pre-FMS training value. CONCLUSION: A 4-week
      protocol of FMS of the expiratory muscles improves voluntary expiratory muscle
      strength significantly, indicating that FMS can be a noninvasive therapeutic
      technology in respiratory muscle training for persons with tetraplegia.

PMID- 11239306
TI  - Functional magnetic stimulation of the colon in persons with spinal cord injury.
AB  - OBJECTIVE: To evaluate the usefulness of functional magnetic stimulation (FMS) as
      a noninvasive method to stimulate the colon in individuals with spinal cord
      injury (SCI). DESIGN: A prospective before-after trial consisting of 2 protocols.
      SETTING: FMS laboratories of 2 SCI centers. PARTICIPANTS: Two able-bodied men and
      13 men with SCI levels ranging from C3 to L1. Protocol 1 consisted of 9 subjects,
      2 of whom were excluded from the analysis. Protocol 2 consisted of 4 subjects.
      INTERVENTION: Commercially available magnetic stimulators with round magnetic
      coils (MCs) were used. Protocol 1 measured the effects of FMS on rectal pressure
      by placing the MC on the transabdominal and lumbosacral regions. Protocol 2
      consisted of a 5-week stimulation period to investigate the effects of FMS on
      total and segmental colonic transit times (CTTs). MAIN OUTCOME MEASURE: An
      increase in rectal pressure and a decrease in CTT by magnetic stimulation.
      RESULTS: Data were averaged and the standard error of the mean was calculated.
      Statistically significant changes in rectal pressure and CTT were also measured.
      Rectal pressures increased from 26.7 +/- 7.44cmH(2)O to 48.0 +/- 9.91cmH(2)O, p
      =.0037, with lumbosacral stimulation, and from 30.0 +/- 6.35cmH(2)O to 42.7 +/-
      7.95cmH(2)O, p =.0015, with transabdominal stimulation. With FMS, the mean CTT
      decreased from 105.2 to 89.4 hours, p =.02. CONCLUSION: FMS is able to stimulate
      the colon and reduce CTT. FMS is a noninvasive, technological advancement for
      managing neurogenic bowel in patients with SCI.

PMID- 11239307
TI  - The effect of aerobic training on rehabilitation outcomes after recent severe
      brain injury: a randomized controlled evaluation.
AB  - OBJECTIVE: To examine the impact of fitness training with recently brain-injured
      inpatients on exercise capacity and functional and psychologic outcome measures.
      DESIGN: A randomized controlled trial of exercise versus relaxation training for
      3 months. Blind assessments were conducted before and after the end of a 12-week
      training program, as well as at follow-up assessment 12 weeks posttraining.
      SETTING: Four regional neurologic inpatient rehabilitation units. PATIENTS: Of
      157 patients recruited 24 +/- 14 weeks after single-incident brain injury, 142
      patients were assessed at week 12, and 128 patients at follow-up. INTERVENTIONS:
      Patients were randomized between cycle ergometer aerobic training and a
      relaxation training control condition, which was theoretically inert with respect
      to cardiovascular fitness. MAIN OUTCOME MEASURES: Validation of exercise training
      (peak work rate, peak heart rate, body mass index); mobility and physical
      function (modified Ashworth scale, Berg balance scale, Rivermead Mobility Index,
      10-m walk velocity); disability and dependency (Barthel index, FIMtrade mark
      instrument, Nottingham Extended Activities of Daily Living); and psychologic
      function (fatigue questionnaire, Hospital Anxiety and Depression Scale). RESULTS:
      Significant improvements in exercise capacity (p <.05) in the exercise training
      group (n = 70) relative to the control group (n = 72) were not matched by greater
      improvements in functional independence, mobility, or psychologic function, at
      either 12 weeks or follow-up. CONCLUSIONS: The benefits of improved
      cardiovascular fitness did not appear to extend to measurable change in function
      or psychologic state.

PMID- 11239308
TI  - Delayed onset of electromyographic activity of vastus medialis obliquus relative
      to vastus lateralis in subjects with patellofemoral pain syndrome.
AB  - OBJECTIVE: To determine whether electromyographic (EMG) onsets of vastus medialis
      obliquus (VMO) and vastus lateralis (VL) are altered in the presence of
      patellofemoral pain syndrome (PFPS) during the functional task of stair stepping.
      DESIGN: Cross-sectional. SETTING: University laboratory. PATIENTS: Thirty-three
      subjects with PFPS and 33 asymptomatic controls. INTERVENTIONS: Subjects ascended
      and descended a set of stairs-2 steps, each 20-cm high-at usual stair-stepping
      pace. EMG readings of VMO and VL taken on middle stair during step up (concentric
      contraction) and step down (eccentric contraction). MAIN OUTCOME MEASURES:
      Relative difference in onset of surface EMG activity of VMO compared with VL
      during a stair-stepping task. EMG onsets were determined by using a computer
      algorithm and were verified visually. RESULTS: In the PFPS population, the EMG
      onset of VL occurred before that of VMO in both the step up and step down phases
      of the stair-stepping task (p <.05). In contrast, no such differences occurred in
      the onsets of EMG activity of VMO and VL in either phase of the task for the
      control subjects. CONCLUSION: This finding supports the hypothesized relationship
      between changes in the timing of activity of the vastimuscles and PFPS. This
      finding provides theoretical rationale to support physiotherapy treatment
      commonly used in the management of PFPS.

PMID- 11239309
TI  - Median "pseudoneurapraxia" at the wrist: reassessment of palmar stimulation of
      the recurrent median nerve.
AB  - OBJECTIVE: To determine the occurrence and effect of incidental deep ulnar nerve
      (DUN) costimulation during palmar stimulation of the recurrent median nerve
      (RMN). DESIGN: Observational. SETTING: Electromyography laboratory. PARTICIPANTS:
      Seventeen asymptomatic adult volunteers (34 hands) and 4 fresh cadaver hands.
      MAIN OUTCOME MEASURES: Median nerve stimulation at the wrist and careful
      incremental surface and subcutaneous (needle) palmar stimulation were performed
      while recording thenar and first dorsal interosseous manus compound muscle action
      potentials. Thenar palm-to-wrist amplitude difference (P -- W Delta) and palm-to
      wrist amplitude ratio (P/W) were compared with published values. Correlation of
      DUN costimulation with falsely elevated P -- W Delta and P/W values was assessed.
      Multiplanar magnetic resonance imaging (MRI) and subsequent dissection of 4 fresh
      cadaver hands was done to measure the distance between the RMN and DUN at the
      palmar stimulation site. RESULTS: Two groups emerged: Group I (63%), with DUN
      stimulation, and II (37%), with no DUN stimulation. When DUN costimulation
      occurred (Group I), there was a statistically significant increase in P -- W
      Delta (p =.002 percutaneous, p =.02 subcutaneous) and P/W (p =.004 percutaneous,
      p =.007 subcutaneous) when compared with previously published data. Combining all
      trials on all hands, 53% and 25% had P -- W Delta values and P/W values that
      exceeded previously published normative data, respectively. The mean distance
      between the DUN and RMN at the palmar stimulation site was determined by
      dissection (1.2cm) and MRI (1.5cm). CONCLUSIONS: Close proximity of the DUN to
      the RMN causes frequent and often unavoidable DUN activation during palmar
      stimulation of the RMN. This inadvertent stimulation may cause a false diagnosis
      of median neurapraxia at the wrist.

PMID- 11239310
TI  - Unipedal stance testing in the assessment of peripheral neuropathy.
AB  - OBJECTIVE: To define further the relation between unipedal stance testing and
      peripheral neuropathy. DESIGN: Prospective cohort. SETTING: Electroneuromyography
      laboratory of a Veterans Affairs medical center and a university hospital.
      PATIENTS: Ninety-two patients referred for lower extremity electrodiagnostic
      studies. MAIN OUTCOME MEASURES: A standardized history and physical examination
      designed to detect peripheral neuropathy, 3 trials of unipedal stance, and
      electrodiagnostic studies. RESULTS: Peripheral neuropathy was identified by
      electrodiagnostic testing in 32%. These subjects had a significantly shorter (p
      <.001) unipedal stance time (15.7s, longest of 3 trials) than the patients
      without peripheral neuropathy (37.1s). Abnormal unipedal stance time (<45s)
      identified peripheral neuropathy with a sensitivity of 83% and a specificity of
      71%, whereas a normal unipedal stance time had a negative predictive value of
      90%. Abnormal unipedal stance time was associated with an increased risk of
      having peripheral neuropathy on univariate analysis (odds ratio = 8.8, 95%
      confidence interval = 2.5--31), and was the only significant predictor of
      peripheral neuropathy in the regression model. Aspects of the neurologic
      examination did not add to the regression model compared with abnormal unipedal
      stance time. CONCLUSIONS: Unipedal stance testing is useful in the clinical
      setting both to identify and to exclude the presence of peripheral neuropathy.

PMID- 11239311
TI  - A focused exercise regimen improves clinical measures of balance in patients with
      peripheral neuropathy.
AB  - OBJECTIVE: To determine the effect of a specific exercise regimen on clinical
      measures of postural stability and confidence in a population with peripheral
      neuropathy (PN). DESIGN: Prospective, controlled, single blind study. SETTING:
      Outpatient clinic of a university hospital. PARTICIPANTS: Twenty subjects with
      diabetes mellitus and electrodiagnostically confirmed PN. INTERVENTION: Ten
      subjects underwent a 3-week intervention exercise regimen designed to increase
      rapidly available distal strength and balance. The other 10 subjects performed a
      control exercise regimen. MAIN OUTCOME MEASURES: Unipedal stance time, functional
      reach, tandem stance time, and score on the activities-specific balance and
      confidence (ABC) scale. RESULTS: The intervention subjects, but not the control
      subjects, showed significant improvement in all 3 clinical measures of balance
      and nonsignificant improvement on the ABC scale. CONCLUSION: A brief, specific
      exercise regimen improved clinical measures of balance in patients with diabetic
      PN. Further studies are needed to determine if this result translates into a
      lower fall frequency in this high-risk population.

PMID- 11239312
TI  - Psychometric properties of the Impact on Participation and Autonomy
      Questionnaire.
AB  - OBJECTIVE: To examine the homogeneity, test-retest reliability, construct
      validity, and concurrent validity of the Impact on Participation and Autonomy
      Questionnaire (IPAQ). DESIGN: Cross-sectional study with a test-retest subsample.
      PATIENTS: One hundred twenty-six persons from 5 diagnostic groups recruited from
      the outpatients clinics of 2 rehabilitation centers and the rehabilitation
      department of an academic hospital. INTERVENTIONS: The IPAQ and 3 other self
      administered questionnaires (Sickness Impact Profile [68-item version], London
      Handicap Scale [LHS], Medical Outcome Study Short-Form Health Survey). The IPAQ
      was completed twice by 75 respondents within approximately 2 weeks. RESULTS: The
      IPAQ addresses autonomy and participation in 5 domains: autonomy indoors, family
      role, autonomy outdoors, social relations, and work and educational
      opportunities. Cronbach's alpha for the several domains ranged between.81 and.91,
      indicating good homogeneity. On item level, weighted kappas ranged between.56
      and.90. On domain level, the test-retest reliability of the IPAQ was good:
      intraclass correlation coefficients ranged between.83 and.91. Convergent validity
      was largely supported by the correlations between 4 domains of the LHS and the
      IPAQ. Discriminant validity was best demonstrated by low correlations between the
      IPAQ and 2 domains of the LHS representing theoretically different constructs.
      CONCLUSION: The IPAQ is a reliable and valid instrument for assessing autonomy
      and participation in chronic disorders. Its responsiveness requires further
      study.

PMID- 11239313
TI  - Quantification of pelvic rotation as a determinant of gait.
AB  - OBJECTIVE: To evaluate the effect of pelvic rotation, originally described as the
      first determinant of gait, on reducing the vertical displacement of the center of
      mass (COM) during comfortable speed walking. DESIGN: Pelvic and lower extremity
      kinematic data during walking were collected. A modified compass gait model
      incorporating measured inputs was used to estimate the effect of pelvic rotation
      on reducing the vertical displacement of the COM. The actual reduction in
      vertical displacement was also calculated. SETTING: A gait laboratory.
      PARTICIPANTS: Thirty able-bodied subjects. MAIN OUTCOME MEASURE: The estimated
      reduction in COM vertical displacement caused by pelvic rotation was compared
      with the actual reduction in COM displacement. RESULTS: The estimated effect of
      pelvic rotation in reducing COM displacement was 2.5 +/- 1.1mm, accounting for
      only 12% of the actual reduction. CONCLUSION: During normal comfortable speed
      walking by able-bodied subjects, pelvic rotation contributes only a small portion
      of the actual reduction in the vertical displacement of the COM compared with a
      compass gait model. Other primary gait factors or determinants are needed to
      explain the actual reduction in vertical displacement of the COM.

PMID- 11239314
TI  - Pelvic mobility when bending forward in standing position: validity and
      reliability of 2 motion analysis devices.
AB  - OBJECTIVE: To evaluate the validity and reliability of 2 measurement devices that
      assess pelvic mobility in persons bending forward while in a standing position.
      DESIGN: Validity and reliability studies. PATIENTS: The validity study included
      10 patients (4 men, 6 women) aged 42 (range, 33--51yr). The reliability study
      included 50 subjects (25 men, 25 women) aged 30 (range, 18--49yr). INTERVENTIONS:
      A 3-dimensional ultrasound motion analyzer (CMS 50) and a spine motion analyzer
      using potentiometers (Rachimetre). METHODS: Two lateral radiographs of the
      patients' lumbosacral junction were taken, the first in neutral position, the
      second in full trunk flexion. Correlations between mobilities assessed by
      radiographs and both devices were evaluated by Spearman's rank correlation
      coefficient. Reliability was studied in healthy volunteers using the intraclass
      coefficient correlation (ICC) and the Bland and Altman plot. RESULTS: Spearman's
      coefficient between radiographic measures and the Rachimetre and the CMS 50
      evaluations were.89 and.81, respectively. For the Rachimetre, ICC was.65 and
      increased with a better standardization of the measurement procedures. For the
      CMS 50, ICC was.85, and the Bland and Altman plot revealed no systematic trend.
      CONCLUSIONS: The Rachimetre and the CMS 50 have acceptable metric properties.
      Because few simple clinical measurements are available to evaluate pelvic
      mobility during trunk flexion in standing position, these 2 devices could be
      useful in the clinical evaluation of low back pain.

PMID- 11239315
TI  - Self-reports and clinician-measured physical function among patients with low
      back pain: a comparison.
AB  - OBJECTIVE: To determine the relationships among self-reported activity limitation
      and clinician-measured functional performance tests. DESIGN: Case series survey.
      SETTING: A referral-based orthopedic spine clinic in Houston, TX. PATIENTS:
      Eighty-three patients (48 women, 35 men) with low back pain (LBP). INTERVENTIONS:
      The Roland-Morris Disability Questionnaire (RMDQ) and a physical performance test
      (PPT) battery. MAIN OUTCOME MEASURES: Self-reported activity limitation (eg,
      walking, bending, getting out of chair, putting on sock, doing heavy jobs) was
      assessed by the RMDQ. Clinician-measured functional performance was assessed with
      the PPT, a battery comprised 6 tests: lumbar flexion range of motion, a 50-foot
      walk at fastest speed, a 5-minute walk, 5 repetitions of sit-to-stand, 10
      repetitions of trunk flexion, and loaded reach task (patients reached forward
      while holding a weight weighing 5% of their body weight). RESULTS: Pearson's
      product-moment correlations between total RMDQ score and each of the performance
      tests ranged from.29 to.41. Point biserial correlations between individual RMDQ
      items and their corresponding performance tests were slightly lower, ranging
      from.20 to.33. CONCLUSION: There were moderate correlations between self-reported
      activity limitation and corresponding clinician-measured performance tests. The
      unique perspective each method provides appears to be useful for a comprehensive
      understanding of physical function in patients with LBP.

PMID- 11239316
TI  - Extensibility and stiffness of the hamstrings in patients with nonspecific low
      back pain.
AB  - OBJECTIVE: To investigate the extensibility and stiffness of the hamstrings in
      patients with nonspecific low back pain (LBP). DESIGN: An experimental design.
      SETTING: A university laboratory for human movement analysis in a department of
      rehabilitation medicine. PARTICIPANTS: Forty subjects, a patient group (20) and a
      healthy control group (20). INTERVENTIONS: Subjects laid supine on an examination
      table with a lift frame, with left leg placed in a sling at the ankle. Straight
      leg raising, pulling force, and activity of hamstring and back muscles were
      recorded with electrodes. Patients indicated when they experienced tension or
      pain. MAIN OUTCOME MEASURES: The lift force, leg excursion, pelvic-femoral angle,
      first sensation of pain, and the electromyogram of the hamstrings and back
      muscles measured in an experimental straight-leg raising set-up. RESULTS: The
      patient group showed a significant restriction in range of motion (ROM) and
      extensibility of the hamstrings compared with the control group. No significant
      difference in hamstring muscle stiffness can be assessed between both groups.
      CONCLUSION: The restricted ROM and the decreased extensibility of the hamstrings
      in patients with nonspecific LBP is not caused by increased muscle stiffness of
      the hamstrings, but determined by the stretch tolerance of the patients.

PMID- 11239317
TI  - Employment status, job characteristics, and work-related health experience of
      people with a lower limb amputation in The Netherlands.
AB  - OBJECTIVES: To describe the occupational situation of people with lower limb
      amputations in The Netherlands and to compare the health experience of working
      and nonworking amputee patients with a nonimpaired reference population. DESIGN:
      Cross-sectional study in which patients completed a questionnaire about their job
      participation, type of job, workplace adjustments to their limb loss, their
      position in the company, and a general health questionnaire. SETTING: Orthopedic
      workshops in The Netherlands with a population of lower limb amputees. PATIENTS:
      Subjects were recruited from orthopedic workshops in the Netherlands. They ranged
      in age from 18 to 60 years (mean, 44.5yr) and had a lower limb amputated at least
      2 years (mean, 19.6yr) before this study. MAIN OUTCOME MEASURES: A self-report
      questionnaire, with 1 part concerning patient characteristics and amputation
      related factors, and the other concerning job characteristics, vocational
      handicaps, work adjustments, and working conditions; and a general health
      questionnaire (RAND-36) to measure health status. RESULTS: Responses were
      received from 652 of the 687 patients (response rate, 95%) who were sent the
      questionnaire. Sixty-four percent of the respondents were working at the time of
      the study (comparable with the employment rate of the general Dutch population),
      31% had work experience but were not presently working, and 5% had no work
      experience. After their amputations, people shifted to less physically demanding
      work. The mean delay between the amputation and the return to work was 2.3 years.
      Many people wished their work was better adjusted to the limitations presented by
      their disability and they mentioned having problems concerning possibilities for
      promotion. Seventy-eight percent of those who stopped working within 2 years
      after the amputation said that amputation-related factors played a role in their
      decision. Thirty-four percent said that they might have worked longer if certain
      adjustments had been made. The health experience of people who were no longer
      working was significantly worse than that of the working people with amputations.
      CONCLUSIONS: Although amputee patients had a relatively good rate of job
      participation, they reported problems concerning the long delay between
      amputation and return to work, problems in finding suitable jobs, fewer
      possibilities for promotion, and problems in obtaining needed workplace
      modifications. People who had to stop working because of the amputation showed a
      worse health experience than working people.

PMID- 11239318
TI  - Acute hypothalamic instability in traumatic brain injury: a case report.
AB  - . Acute hypothalamic instability occurs in patients with traumatic brain injury
      (TBI). It usually occurs in the form of autonomic dysfunction syndrome (also
      known as diencephalic seizures or paroxysmal sympathetic storms); however, there
      are other causes of acute hypothalamic instability of which the clinician must be
      aware. Neuroleptic malignant syndrome, malignant hyperthermia, autonomic
      dysfunction syndrome, and lethal catatonia are all syndromes that clinically
      present as signs and symptoms of acute hypothalamic instability. Because of the
      lethal potential of these syndromes, clinicians who care for patients with TBI
      must be aware of the various syndromes, their clinical presentation, and their
      treatment. We present a case of life-threatening acute hypothalamic instability
      in a patient with TBI.

PMID- 11239319
TI  - Baastrup's disease correlating with diffuse lumbar paraspinal atrophy: a case
      report.
AB  - Baastrup's disease ("kissing spine") is an x-ray finding that has been considered
      a possible cause of low back pain (LBP) since the 1930s. Its etiology is unknown,
      and there are no reports of muscle or soft tissue changes associated with it.
      This case report concerns a 57-year-old man with chronic LBP, stiffness, and
      indurated skin over the back. He had classic sclerotic changes between the
      spinous processes on x-ray, which is consistent with Baastrup's disease. Computed
      tomography (CT) and electromyography were performed. CT showed profound fatty
      replacement of the paraspinal musculature. An electromyography report showed
      severe isolated paraspinal denervation. This case suggests that diffuse fatty
      replacement of the paraspinal muscles, perhaps due to a compartment syndrome or
      other vascular event, may have a role in the pathogenesis of Baastrup's disease.

PMID- 11239320
TI  - Sciatic neuropathy caused by disorder of a nutrient artery: a case report of
      thromboembolism secondary to profunda femoral artery aneurysm.
AB  - This report describes a case of sciatic neuropathy caused by an obstruction of
      the nutrient artery of the nerve. The patient was a 76-year-old man who had an
      aneurysm in his right thigh and suddenly complained of pain and weakness in his
      right leg. Computed tomography scan and ultrasonography of the right thigh showed
      an aneurysm with a thrombus in the lumen of the profunda femoral artery. His
      symptoms did not immediately improve after the aneurysm had been resected, and
      were consistent with right sciatic neuropathy. Recovery of strength of the right
      tibialis anterior muscle from 0/5 to 3/5 required 12 months. In this case,
      thromboemboli from the aneurysm were thought to have obstructed the profunda
      femoral artery, which supplied the sciatic nerve via perforating arteries.

PMID- 11239321
TI  - Functional changes and adverse reactions after successful treatment of hereditary
      myokymia: a case report.
AB  - Myokymia is a vermiform motion of muscle that can be found in conditions in which
      there is pathology to the peripheral nerve to that muscle. There are inherited
      syndromes that can present with muscle cramping and myokymia that have been
      described, but little information exists on long-term follow-up. In this case
      study, a 12-year-old girl had an inherited form of myokymia, as determined by
      clinical examination, electromyographic findings, and family history. The mode of
      inheritance appeared to be autosomal dominant with reduced penetrance.
      Carbamazepine was used successfully to treat this disorder. Measurements were
      made of strength and endurance before and after treatment; significant
      improvement was seen in endurance with little effect on strength. The patient was
      able to discontinue carbamazepine without return of symptoms and subsequently was
      not limited in her activities. Return of symptoms was seen with prednisone
      treatment for exacerbated asthma. The symptoms resolved with restarting the
      carbamazepine and weaning of the prednisone. Discussion is presented on the
      possible mechanism by which anticonvulsant and steroid therapy exert their
      effects on myokymia.

PMID- 11239322
TI  - Solitary rectal ulcer syndrome (colitis cystica profunda) in spinal cord injury
      patients: 3 case reports.
AB  - Clinically indicated endoscopic examinations of 56 patients with spinal cord
      injury (SCI) (31 for bleeding) were performed over a 3-year period, of which 3
      (6%) showed solitary rectal ulcer syndrome (SRUS). The presentation was rectal
      bleeding or mucoid discharge. The endoscopic appearance was multiple pseudopolyps
      and occasional mucosal ulcers extending proximally 8 to 40cm from the anus.
      Mucosal biopsy specimens showed distorted mucosal glands and displaced smooth
      muscle fibers wrapping around the glands, the hallmark of SRUS. The affected
      patients had routinely used suppositories and digital stimulation for bowel care
      and had been paralyzed 7 to 50 years. None had rectal prolapse. These cases show
      that SRUS (colitis cystica profunda) can be found among patients with SCI.

PMID- 11239323
TI  - Focal intense brief transcutaneous electric nerve stimulation for treatment of
      radicular and postthoracotomy pain.
AB  - OBJECTIVE: To assess the efficacy of focal intense brief transcutaneous electric
      nerve stimulation in 2 groups of patients with neuropathic pain. DESIGN: Electric
      stimulation was delivered with a small stylus electrode pressed against the skin
      paravertebrally in the radiculopathy group and along the surgical incision in the
      postthoracotomy neuralgia group. A before-after treatment design was conducted
      with a verbal pain rating scale. SETTING: Outpatient multidisciplinary pain
      clinic at a Midwestern Veterans Affairs medical center. PARTICIPANTS: Fourteen
      consecutive patients with well-documented radiculopathy and 4 consecutive
      patients with postthoracotomy neuralgia. RESULTS: Statistically significant
      differences were found in both patient groups, with posttreatment scores
      reflecting less pain than pretreatment scores for every patient. CONCLUSIONS:
      Patients reported reduced pain ratings following this stimulation technique.
      Further study of this inexpensive, noninvasive, outpatient technique is needed.

PMID- 11239324
TI  - Energy expenditure of wheeling and walking during prosthetic rehabilitation in a
      woman with bilateral transfemoral amputations.
AB  - OBJECTIVE: To compare the energy expenditure of locomotion by wheelchair with
      that required for prosthetic ambulation in a person with bilateral transfemoral
      (TF) amputations. DESIGN: Observational, single patient, descriptive. SETTING: An
      80-meter long rectangular hallway in a rehabilitation unit. PATIENT: A 41-year
      old woman with bilateral TF amputations that were performed 79 days before her
      admission to the rehabilitation unit. MAIN OUTCOME MEASURES: The oxygen uptake,
      oxygen cost, heart rate, speed, cadence, and stride length of walking measured
      during a 4-month course of prosthetic rehabilitation. Five locomotion conditions
      were evaluated: (1) wheelchair propulsion, (2) walking with short-leg prostheses
      (stubbies) and a walker, (3) long-leg prostheses and a walker, (4) long-leg
      prostheses without knee mechanism and axillary crutches, and (5) long-leg
      prostheses with right polycentric knee and left locked knee and axillary
      crutches. A portable and telemetric system was used to measure the metabolic
      parameters. An arm ergometry graded exercise test was performed at the end of
      rehabilitation. RESULTS: Oxygen cost (range, 466%--707% of that of wheeling) and
      heart rate (range, 106%--116% of that of wheeling) were higher during walking
      with various combinations of prostheses and walking aids. The speed of prosthetic
      walking was only 24% to 33% of that of wheeling. Our patient preferred using a
      wheelchair to prosthetic walking after discharge. CONCLUSIONS: People with
      bilateral TF amputations require very high cardiorespiratory endurance to fulfill
      the energy demand during prosthetic rehabilitation. The high energy cost of
      prosthetic walking will limit its application in daily activities.

PMID- 11239325
TI  - Treatment of upper motoneuron plantarflexion contractures by using an adjustable
      ankle-foot orthosis.
AB  - OBJECTIVE: To assess the effectiveness of an adjustable ankle-foot orthosis in
      the treatment of plantarflexion contractures after central nervous system injury
      or disease. DESIGN: Prospective, nonrandomized, interventional trial. SETTING:
      University medical center's acute inpatient rehabilitation hospital.
      PARTICIPANTS: Nine ankles with plantarflexion contractures that could not be
      passively reduced to less than neutral position occurring in 6 patients with
      stroke or other acquired brain injury. INTERVENTION: To assure differentiation
      between spastic deformity and true contracture, patients received a 2% lidocaine
      block of the posterior tibial nerve. The adjustable ankle-foot orthosis was then
      applied on the affected ankle for 23 hours per day for 14 days. Adjustments to
      increase dorsiflexion passive range of motion (PROM) ranged from 0 degrees to 4.5
      degrees and were attempted every 48 to 72 hours. MAIN OUTCOME MEASURES:
      Dorsiflexion PROM at the ankle with the knee extended. RESULTS: Increased PROM
      (average, 20.1 degrees; range, 6 degrees--36 degrees ) was statistically
      significant (p =.0078). Complications related to pressure with erythema or
      blister formation associated with pain occurred in 44% of treated ankles at some
      time during the 2-week trial period. CONCLUSION: Plantarflexion contractures can
      be significantly reduced by using the adjustable ankle-foot orthosis with minimal
      complications.

PMID- 11239326
TI  - Effect of seat cushion on dynamic stability in sitting during a reaching task in
      wheelchair users with paraplegia.
AB  - OBJECTIVES: To examine the effects of seat cushions on dynamic stability in
      sitting during a controlled reaching task by wheelchair users with paraplegia.
      DESIGN: A randomized, controlled test. SETTING: Rehabilitation center.
      PARTICIPANTS: Nine wheelchair users with paraplegia. INTERVENTIONS: Three types
      of cushions--an air flotation, a generic contoured, and a flat polyurethane foam-
      were tested during a controlled reaching task in ipsilateral and contralateral
      directions, at 45 degrees from the sagittal plane in the anterolateral direction.
      Center of pressure (COP) coordinates were monitored by using a pressure
      measurement system as well as a force platform under seat. MAIN OUTCOME MEASURES:
      Trajectory of COP, maximal distance covered by COP, maximal velocity of COP; and
      the index of asymmetry between right and left maximal pressure under ischial
      tuberosities. RESULTS: The generic contoured cushion allowed the COP to cover
      significantly (p <.02) a larger distance (81 +/- 28mm) when compared with the air
      flotation (63 +/- 25mm) or the flat foam (61 +/- 29mm) cushions. The COP velocity
      was significant (p <.05) for the generic contoured cushion (.14 +/-.05m/s) versus
      the air flotation (.10 +/-.04m/s) or the flat-foam (.10 +/-.03m/s) cushions. The
      index of asymmetry was higher for the generic contoured and the flat foam
      cushions. During reaching, maximal pressure under ipsilateral ischial tuberosity
      was significantly higher for the flat foam (275 +/- 70mmHg) and the generic
      contoured (235 +/- 81mmHg) cushions, when compared with the air flotation cushion
      (143 +/- 51mmHg). CONCLUSION: Seat cushions can significantly affect sitting
      balance during reaching tasks. This study provided an objective method to assess
      the dynamic stability of wheelchair users when they perform activities of daily
      living requiring reaching. These findings have implications for wheelchair
      seating recommendations, especially seat cushion selection.

PMID- 11239327
TI  - Effects of knee bracing on the functional performance of patients with anterior
      cruciate ligament reconstruction.
AB  - OBJECTIVE: To compare the functional performance of subjects with unilateral
      anterior cruciate ligament (ACL) reconstruction. DESIGN: Cross-sectional
      comparative clinical trial. SETTING: A physical therapy outpatient department.
      SUBJECTS: Thirty-one subjects with unilateral ACL reconstruction for more than 5
      months. INTERVENTION: Patients under 3 bracing conditions: (1) DonJoy Brace, (2)
      mechanical placebo brace, or (3) no brace. Running and turning 10 times on a 22
      meter figure-8 runway, and running and jumping (and landing) on a semicircular
      path. MAIN OUTCOME MEASURES: Speed of running and turning, speed of running and
      jumping, and accuracy of landing after the jump. RESULTS: Subjects performed
      similarly in conditions 1 and 2 in all the tests, but the speeds of running and
      turning were significantly slower in conditions 1 and 2 than condition 3 (p =.008
      -.000). Results of the run and jump tests were not different among all
      conditions. CONCLUSION: Knee bracing may not improve functional performance of
      subjects 5 months after ACL reconstruction. The use of such a brace could
      actually slow down running and turning, irrespective of the mechanical
      constraints of the brace. These functional outcomes need to be noted when such a
      brace is used on this group of subjects.

PMID- 11239328
TI  - The platform transfer splint: 2 case reports of a mobility aide for persons with
      arm injuries or conditions.
AB  - Limited or impaired mobility is a major obstacle to maximizing length of stay
      efficiency for inpatient rehabilitation. Trauma patients and others with multiple
      limb impairments present a mobility challenge to all rehabilitation centers. Of
      particular concern are patients with forearm fractures who are nonambulatory.
      With shorter inpatient stays, patients are being discharged home or to other
      settings with continued weight-bearing restrictions. These patients put great
      demands on their caregivers as a result of their limited mobility. The Platform
      Transfer Splint (PTS) has been developed to overcome limitations seen in this
      patient population. It is an upper extremity splint that allows weight bearing
      through the humerus for patients with impairments of the forearm or hand. With
      use of the PTS, patients can become independent in transfers and wheelchair
      propulsion. Two case studies are presented to show the impact of the PTS on
      patient mobility and discharge disposition. Fabrication of the splint is also
      discussed.

PMID- 11239330
TI  - Acquired limb deficiencies. 1. Acquired limb deficiencies in children and young
      adults.
AB  - This self-directed learning module highlights prosthetic treatment considerations
      and challenges in children and young adults. It is part of the chapter on
      acquired limb deficiencies in the Self-Directed Physiatric Education Program for
      practitioners and trainees in physical medicine and rehabilitation. This article
      specifically focuses on prosthetic considerations for a child experiencing a
      mutilating traumatic amputation, examines the rationale for limb salvage versus
      surgical amputation for malignant bone tumors, discusses the unique management
      options available for patients undergoing hip disarticulation due to a tumor, and
      highlights the complications associated with amputations resulting from trauma
      and malignancies. OVERALL ARTICLE OBJECTIVE: To summarize prosthetic treatment
      considerations and challenges in children and young adults.

PMID- 11239331
TI  - Acquired limb deficiencies. 2. Perioperative management.
AB  - This self-directed learning module highlights recent advances in the evaluation
      and management of complications arising from diabetes and peripheral vascular
      disease leading to amputation. It is part of the chapter on acquired limb
      deficiencies in the Self-Directed Physiatric Education Program for practitioners
      and trainees in physical medicine and rehabilitation. This article includes
      discussion of comorbid conditions that may have an impact on the prosthetic
      rehabilitation of a transtibial amputee. It also offers essential information
      regarding perioperative management of an upper extremity amputee. OVERALL ARTICLE
      OBJECTIVE: To review recent advances in the evaluation and management of
      complications arising from diabetes and peripheral vascular disease leading to
      amputation.

PMID- 11239332
TI  - Acquired limb deficiencies. 3. Prosthetic components, prescriptions, and
      indications.
AB  - This self-directed learning module highlights indications for prosthetic
      components and prescription formulation for adults with acquired limb deficiency.
      It is part of the chapter on acquired limb deficiencies in the Self-Directed
      Physiatric Education Program for practitioners and trainees in physical medicine
      and rehabilitation. Advantages and disadvantages of specific components of upper
      and lower limb prostheses are discussed, and a sample prescription sheet for
      upper limb devices is included. Recent innovations in terminal devices for upper
      limb prostheses are reviewed. Special considerations for the adult with acquired
      multilimb deficiency are also examined. OVERALL ARTICLE OBJECTIVE: To describe
      indications for prosthetic components and prescription formulation for adults
      with acquired limb deficiency.

PMID- 11239333
TI  - Acquired limb deficiencies. 4. Troubleshooting.
AB  - This self-directed learning module offers practical analyses of and solutions for
      common clinical problems of amputees. It is part of the chapter on acquired limb
      deficiencies in the Self-Directed Physiatric Education Program for practitioners
      and trainees in physical medicine and rehabilitation. The information presented
      here has been designed to be useful also to other interested professionals,
      including prosthetists, physical therapists, occupational therapists, and nurses.
      Topics covered include the management of typical obstacles encountered in upper
      limb amputees, and the diagnosis and treatment of phantom and residual limb pain.
      Diagnostic and treatment approaches to skin breakdown in the transtibial amputee
      and to knee instability in the transfemoral amputee are also presented. OVERALL
      ARTICLE OBJECTIVE: To analyze common clinical problems of amputees.

PMID- 11239334
TI  - Sports and recreation for persons with limb deficiency.
AB  - Opportunities for persons with limb deficiency to participate in sport and
      recreational activities have increased dramatically over the past 20 years.
      Various factors have contributed to this phenomenon, including an increased
      public interest in sports and fitness as well as improvements in disability
      awareness. An even more essential element has been a consumer-driven demand for
      advances in prosthetic technology and design. Whether the activity is a music
      performance, a friendly round of golf, or a high-level track-and-field
      competition, the benefits of participation in sports and recreation are numerous
      both at the individual and at the societal level. This article provides an
      overview of the development and scope of sport and recreational opportunities
      available to persons with limb deficiency. In addition, specific prosthetic
      considerations for several common sport and recreational activities are presented
      in a case-discussion format. OVERALL ARTICLE OBJECTIVE: To review the development
      and scope of sport and recreational opportunities available to persons with limb
      deficiency.

PMID- 11239335
TI  - Cardiopulmonary rehabilitation and cancer rehabilitation. 1. Cardiac
      rehabilitation.
AB  - This self-directed learning module highlights cardiac rehabilitation issues
      facing able-bodied populations. It is part of the chapter on cardiovascular,
      pulmonary, and cancer rehabilitation in the Self-Directed Physiatric Education
      Program for practitioners and trainees in physical medicine and rehabilitation.
      This article focuses on various aspects of the management of cardiac disease and
      rehabilitation, including medication, exercise, risk-factor modification,
      secondary prevention, and surgery. Topics discussed include myocardial
      infarction, coronary artery disease, cardiomyopathy, and angina. New advances
      covered in this article include the various phases of cardiac rehabilitation,
      data on lifestyle adaptations for cardiac disease, and recent surgical advances
      for the treatment of severe heart failure. OVERALL ARTICLE OBJECTIVE: To review
      aspects of the management of cardiac disease and rehabilitation, including
      medication, exercise, risk-factor modification, secondary prevention, and
      surgery.

PMID- 11239336
TI  - Cardiopulmonary rehabilitation and cancer rehabilitation. 2. Cardiac
      rehabilitation in disabled populations.
AB  - This self-directed learning module highlights the clinical characteristics,
      medical treatment, and rehabilitation interventions of several cardiac scenarios
      encountered in physiatric practice. It is part of the chapter on cardiac
      rehabilitation in the Self-Directed Physiatric Education Program for
      practitioners and trainees in physical medicine and rehabilitation. This article
      discusses myocardial infarction during amputation, stroke as a result of cardiac
      surgery, myocardial perfusion defects in spinal cord injury, and heart murmur in
      Down syndrome. It also covers current medical management and the benefits of
      comprehensive rehabilitation and interventions for specific impairments seen in
      these conditions. OVERALL ARTICLE OBJECTIVE: To describe the clinical
      characteristics, medical treatment, and rehabilitation interventions of 4 cardiac
      scenarios encountered in physiatric practice.

PMID- 11239338
TI  - Cardiopulmonary rehabilitation and cancer rehabilitation. 4. Oncologic
      rehabilitation.
AB  - This self-directed learning module highlights the treatment and rehabilitation of
      patients with cancer by means of a case study format. It is part of the chapter
      on cardiac, pulmonary, and cancer rehabilitation in the Self-Directed Physiatric
      Education Program for practitioners and trainees in physical medicine and
      rehabilitation. This article reviews medical and rehabilitation issues in
      patients with various types of cancer. Cases were selected to cover problems seen
      in both younger and older patient populations. Identification of common sequelae
      of cancer and cancer treatments, associated rehabilitation challenges, and
      appropriate interventions are included. OVERALL ARTICLE OBJECTIVE: To summarize
      the medical and rehabilitation issues in patients with various types of cancer.

PMID- 11239337
TI  - Cardiopulmonary rehabilitation and cancer rehabilitation. 3. Pulmonary
      rehabilitation.
AB  - This self-directed learning module highlights assessment and therapeutic options
      in the rehabilitation of patients with pulmonary diseases and in the pulmonary
      management of neurologic disorders. It is part of the chapter on cardiovascular,
      pulmonary, and cancer rehabilitation in the Self-Directed Physiatric Education
      Program for practitioners and trainees in physical medicine and rehabilitation.
      Topics reviewed in the rehabilitation of pulmonary diseases include
      interdisciplinary programming for patients with chronic obstructive pulmonary
      disease, the role of rehabilitation in lung transplantation and lung volume
      reduction surgery, and chest physiotherapy and other rehabilitation strategies
      for patients with cystic fibrosis. The pulmonary management of several
      neuromuscular disorders is discussed, with attention to the recognition of early
      pulmonary dysfunction, the role of ventilatory muscle training, and the
      indications and options for assisted ventilation. OVERALL ARTICLE OBJECTIVE: (a)
      To review the assessment and therapeutic options in the rehabilitation of
      patients with pulmonary diseases and (b) to describe the pulmonary management of
      neurologic disorders.

PMID- 11239339
TI  - Exercise, cardiovascular disease, and chronic heart failure.
AB  - In addition to patients with coronary artery disease, high-risk patients with
      severe congestive heart failure can benefit from rehabilitation. Traditionally,
      such patients were excluded from rehabilitation, but resistive exercise, higher
      intensity programs, and interval training have now been safely conducted.
      Emerging data indicate that exercise training results in a number of improved
      physiologic and psychologic indices, including neural control, quality of life,
      exercise tolerance, ventricular function, skeletal muscle physiology, peripheral
      blood flow, and endothelial function. This review explores these beneficial
      outcomes through an assessment of therapeutic approaches, with special emphasis
      on the unique clinical characteristics of patients with congestive heart failure.
      OVERALL ARTICLE OBJECTIVE: To describe the benefits and the evolving role of
      cardiac rehabilitation for patients with congestive heart failure.

PMID- 11239340
TI  - Pain management in cancer rehabilitation.
AB  - Significant pain is experienced by the majority of cancer patients during the
      course of their illness. Despite the widespread availability of effective
      therapy, undertreatment remains common. Opioid pharmacotherapy has emerged as the
      mainstay of cancer pain management. Coanalgesic administration, disease-modifying
      therapies, and interventional strategies may be used concurrently to augment pain
      relief. Adequate pain management is a requisite condition for successful
      rehabilitation of patients with neoplasms. OVERALL ARTICLE OBJECTIVE: To describe
      common cancer- and treatment-related pain syndromes and the analgesic approaches
      commonly utilized in the management of cancer pain.

PMID- 11239341
TI  - Straight anterior instability: Lesions of the middle glenohumeral ligament.
AB  - PURPOSE: Thirty-three patients with avulsions of the middle glenohumeral ligament
      repaired using arthroscopic techniques were evaluated to determine the mechanism
      of injury, physical examination findings, and efficiency of repair techniques in
      this patient cohort. Type of Study: In a retrospective consecutive case series,
      33 patients with symptomatic anterior subluxation of the glenohumeral joint were
      found to have a history, physical examination, and diagnostic arthroscopy
      consistent with isolated avulsions of a type I middle glenohumeral ligament.
      METHODS: The mechanism of injury was either repetitive overhead activity (17
      patients) or a forced hyperextension in neutral rotations (16 patients). Physical
      examination was positive for a load and shift (fulcrum) testing of the middle
      glenohumeral ligament and "Whipple" testing of the anterior supraspinatus tendon.
      Magnetic resonance imaging with or without gadolinium was positive for anterior
      labral tearing in all 20 patients in which the test was performed. RESULTS:
      Arthroscopic repair of the detached labrum resulted in decreased pain and
      improved function in all patients. Thirty-one of the patients were well
      satisfied, 1 was improved, and 1 was dissatisfied with the repair. CONCLUSIONS:
      Thirty-one of 33 patients graded as excellent, 1 good, and 1 poor in this study.
      Surgical repair of avulsions of the middle glenohumeral ligament provides
      satisfactory results in a majority of patients.

PMID- 11239342
TI  - Arthroscopic treatment of multidirectional glenohumeral instability: 2- to 5-year
      follow-up.
AB  - PURPOSE: We present the results of a prospective study evaluating arthroscopic
      technique in repairing multidirectional glenohumeral instability. Type of Study:
      Case series. METHODS: The 47 patient study group consisted of 26 men and 21
      women. Inclusion criteria were multidirectional glenohumeral instability
      diagnosed on physical examination and at arthroscopy. Exclusion criteria were
      unidirectional anterior or posterior instability and prior instability operation.
      Four patients declined to participate in the study. The average age at the time
      of operation was 30 years (range, 15 to 56 years). The average interval from
      operation to final evaluation was 35 months (range 26 to 67 months). The American
      Shoulder and Elbow Surgeons (ASES) Shoulder Index, Constant, Rowe, and UCLA
      scores were recorded preoperatively and at final evaluation. RESULTS:
      Preoperatively, no patients were rated overall as good to excellent according to
      the Rowe scale; at final follow-up 94% (44 of 47 patients) were rated as good to
      excellent. One patient was considered a failure of the index operation due to
      persistent instability and underwent a second operative procedure. One patient
      noted a loss of strength during sports, and 2 patients had pain that limited
      their throwing ability. The ASES Shoulder Index improved to 94.7 from 45.4 (P
      =.001). The absolute Constant score improved to 91.7 from 60 (P =.001). The Rowe
      score improved to 93.7 from 14.2 (P =.001). The UCLA total score improved to 33.1
      from 17.4 (P =.001). Average passive external rotation at 90 degrees abduction
      measured 88.2 degrees. Twenty-two of 26 patients (85%) returned to their desired
      levels of sports following the operations. CONCLUSIONS: Patients with
      multidirectional glenohumeral instability have multiple lesions within the
      shoulder and the surgeon must individualize the operative treatment. Arthroscopic
      surgery produced successful results in 44 of 47 patients.

PMID- 11239343
TI  - Neurovascular risk of bicortical tibial drilling for screw and spiked washer
      fixation of soft-tissue anterior cruciate ligament graft.
AB  - PURPOSE: As the use of soft-tissue anterior cruciate ligament (ACL) grafts,
      including hamstring grafts, has become more prominent and the benefits of
      aggressive rehabilitation have become clear, maximizing fixation with screw and
      spiked washers is important. Bicortical fixation may be superior. We were
      concerned about potential neurovascular risks and designed this study to define
      the posterior neurovasculature structures at risk when drilling for bicortical
      tibial screw fixation during ACL reconstruction. Type of Study: Consecutive
      sample. METHODS: We placed the tibial tunnel arthroscopically in 10 cadaveric
      knees using a standard tibial drill guide. Accurate tibial tunnel position was
      documented in each knee by lateral radiograph. A 4.5-mm bicortical drill hole was
      placed perpendicular to the tibial surface 1 cm distal to the tibial tunnel. The
      distances from the posterior tibial drill exit point to nearby neurovascular
      structures were measured with a caliper. RESULTS: The closest structure to the
      exit point was the bifurcation of the popliteal artery/vein (11.4 +/- 0.6 mm;
      range, 8.4 to 14.0 mm). The next closest was the anterior tibial vein (11.7 +/-
      1.6 mm; range, 3.5 to 22.8 mm). The closest any individual hole came to a
      neurovascular structure was 3.5 mm from the anterior tibial vein. CONCLUSIONS:
      Bicortical drilling for fixation of soft tissue grafts appears reasonably safe.
      The structures at greatest risk for injury are the bifurcation of the popliteal
      artery/vein and the anterior tibial vein.

PMID- 11239344
TI  - Patellar versus hamstring tendons in anterior cruciate ligament reconstruction: A
      meta-analysis.
AB  - PURPOSE: To compare the outcome of ACL reconstuction using patellar tendon (PAT)
      to that when using hamstring tendons. Type of Study: Meta-analysis of controlled
      trials of patellar tendon versus hamstring tendons for ACL reconstruction.
      METHODS: Meta-analysis is a systematic method for statistical analyses that
      allows compilation of combined data from various independent studies. This allows
      one to assess the potential benefits of various treatments when conclusions based
      on individual studies are difficult to assess. We conducted a meta-analyses (M-A)
      using controlled trials (CTs) to determine if there are differences between the 2
      methods. Although both surgical techniques have potential for good results, we
      hypothesized that there are differences in outcomes between these techniques. We
      included CTs that used standard evaluation techniques with a minimum 2-year
      follow-up. Outcomes evaluated included: return to preinjury level of activity, KT
      testing, Lachman scores, pivot shift scores, range of motion (ROM) loss in
      flexion and extension, complications, and failures. Relative risks for each
      outcome were calculated for each study and pooled across studies using a fixed
      effects method. RESULTS: Four studies fulfilled our inclusion criteria. Relative
      risks with 95% confidence intervals and P values were obtained for each of the
      outcomes listed above. The results show significant differences between PAT and
      semitendinosus and gracilis tendon (ST&G) reconstructions. PAT patients have a
      greater chance of attaining a statically stable knee (as measured by KT) and
      nearly a 20% greater chance of returning to preinjury activity levels.
      CONCLUSIONS: Although both techniques, as performed in the late 1980s and early
      1990s, yielded good results, PAT reconstuction led to higher postoperative
      activity levels and greater static stability than hamstring reconstruction. This
      is statistically significant based on this meta-analysis.

PMID- 11239345
TI  - A new endoscopic posterior cruciate ligament reconstruction: Minimization of
      graft angulation.
AB  - PURPOSE: The purpose of this report is to present a new surgical technique for
      endoscopic posterior cruciate ligament (PCL) reconstruction and to elucidate the
      preliminary results. Surgical Technique: The concept of this surgical technique
      is to minimize the graft angulation at the inner edge of the bone tunnel. The
      tibial entry point of the guide pin is under the tibial lateral subcondylar flare
      approximately 1 to 2 cm anterior to the posterior cortex and 4 cm distal to the
      joint surface. This creates less graft angulation on the posterior aspect of the
      tibia. A new drill system has been devised to allow antegrade femoral drilling
      starting from inside the notch. This method also allows better femoral tunnel
      orientation. As a substitute graft material, we use autogenous hamstring tendons,
      and we secure them with an EndoButton (Smith & Nephew, Mansfield, MA) and post
      screw. METHODS: Since 1995, 40 knees have undergone endoscopic PCL
      reconstruction. Twenty-one patients were evaluated after a minimum follow-up of 1
      year (17.9 +/- 7.7 mo). The clinical evaluation was performed using the
      International Knee Documentation Committee (IKDC) form. RESULTS: The range of
      motion was rated as A for 17 cases, B in 3 cases, and C in one case. The total
      anteroposterior translation (KT-1000, manual-maximum) showed a range of 1.0 to
      5.5 mm (mean, 2.8 mm). The ratings of the ligament examination were A in 9 cases
      and B in 12 cases. The final IKDC evaluation was A (normal) in 3 cases, B (nearly
      normal) in 17 cases, and C (abnormal) in 1 case. CONCLUSIONS: A good clinical
      outcome was achieved with our endoscopic PCL reconstruction. The reduction of the
      graft angulation may contribute to the good results for PCL reconstruction.

PMID- 11239346
TI  - Evaluation of healing of the injured posterior cruciate ligament: Analysis of
      instability and magnetic resonance imaging.
AB  - PURPOSE: Knees with an acute posterior cruciate ligament (PCL) injury and soft
      endpoint on posterior drawer test often develop less instability and a firm
      endpoint at later follow-up. This type of healing is rarely seen in the acutely
      injured anterior cruciate ligament (ACL) and seems to be a unique feature of
      healing for PCL injury. The purpose of this study was to explore the healing
      process of the injured PCL by means of instability measurement and magnetic
      resonance imaging (MRI). Type of study: Consecutive sample. METHODS: Forty-eight
      acute PCL deficient knees were followed up and evaluated. We evaluated the
      detection of a so-called firm endpoint using a posterior drawer test. We also
      determined the degree of posterior sag and categorized them as 3 grades.
      Quantitative assessment of total anteroposterior (AP) translation of the tibia
      with a KT-1000 knee arthrometer (MedMetric, San Diego, California) was performed
      by manual maximum AP drawer test with the knee flexed 70 degrees. The continuity
      of the PCL was evaluated with sagittal and coronal T1- and T2-weighted MRIs.
      RESULTS: Thirty-three (69%) cases exhibited a so-called firm endpoint with a
      posterior drawer test. These cases showed statistically less total AP translation
      (mean, 7.0 mm) in KT-1000 evaluation, compared with 15 cases without an endpoint
      (mean, 11.9 mm). In addition, 36 cases (75%) with continuous low-intensity MRI
      showed statistically less AP translation (mean 7.6 mm), compared with 12 cases
      (mean 11.4 mm) with disrupted PCL image. CONCLUSIONS: These results suggest that
      a high percentage of acutely injured PCLs are likely to develop somewhat slack
      but continuous ligament-like tissue, and this continuous PCL-like tissue might
      function as a posterior restraint of the tibia to certain extent. The elongated
      but continuous PCL might partly explain the relatively favorable prognosis of
      this injury.

PMID- 11239347
TI  - The sequelae of salvaged nondegenerative peripheral vertical medial meniscus
      tears with anterior cruciate ligament reconstruction.
AB  - PURPOSE: To determine the clinical sequelae of nondegenerative peripheral
      vertical medial meniscus tears treated with abrasion and trephination alone
      (stable tears) or suture repair (unstable tears). Type of Study: Cohort follow
      up. METHODS: At the time of anterior cruciate ligament reconstruction, 548
      patients had nondegenerative peripheral vertical medial meniscus tears that were
      either left unsutured or repaired. Of 548 menisci, 233 were stable and were
      abraded and trephined (AT group), 139 were stable and left in situ (Situ group),
      and 176 were unstable and were repaired with sutures (Suture group). An unstable
      tear was defined as a torn meniscus that could be displaced into the
      intercondylar notch with a probe. Patients who had no medial or lateral meniscal
      tears at the time of ACL reconstruction served as a control population (No Tear
      group, n = 526). Subjective follow-up was obtained with a modified Noyes
      questionnaire. RESULTS: Objective follow-up was obtained at a mean of 4.8 +/- 1.7
      years postoperatively. Subjective follow-up was obtained at a mean of 7.3 +/- 3.4
      years postoperatively. At a mean of 3.7 years (range, 4 months to 10.7 years)
      after the reconstruction, a subsequent arthroscopy was required for 14 patients
      (6.0%) in the AT group, 15 patients (10.8%) in the Situ group, 24 patients
      (13.6%) in the Suture group, and 15 patients (2.9%) in the No Tear group; these
      numbers were not statistically significant. The mean total subjective score was
      not statistically significantly different between groups. CONCLUSIONS: Repaired
      unstable peripheral vertical medial meniscus tears have a failure rate of 13.6%,
      most retears occurring more than 2 years after repair. Of stable peripheral
      vertical medial meniscus tears treated with abrasion and trephination, most (94%)
      remain asymptomatic without stabilization.

PMID- 11239348
TI  - Clinical, radiologic, and arthroscopic assessment of discoid lateral meniscus.
AB  - PURPOSE: To establish the common clinical and radiologic features of discoid
      lateral meniscus in a setting where magnetic resonance imaging was not routinely
      possible because of cost and access. Arthroscopy was used to confirm the
      diagnosis. Type of Study: Retrospective study of group of patients with discoid
      lateral meniscus as the diagnosis. METHODS: Of 1,643 arthroscopies of the knee
      performed between January 1993 and January 1999, 87 patients (95 knees) with
      discoid lateral meniscus were studied with regard to their clinical presentation
      and radiologic features. Arthroscopy was used for confirmation of diagnosis,
      classification of types of discoid lateral meniscus and pattern of tears, and for
      treatment. RESULTS: Of all the knee arthroscopies, 5.8% involved patients with
      discoid lateral meniscus. The average age of patients at presentation (24.7
      years), contributed to a 67.3% incidence of associated tears. Tears were more
      frequently associated with patients older than 15 years, which was statistically
      significant (P =.0005). The most common clinical features were pain and joint
      line tenderness. In this series, the incidence of radiologic findings was high
      (53.9%). CONCLUSIONS: The high incidence of tears is attributable to the late
      presentation. The incidence of radiologic findings in this series is high.

PMID- 11239349
TI  - Histopathologic assessment of healed osteochondral fractures.
AB  - PURPOSE: To assess the histopathologic features of healed tissue to define its
      biological and biomechanical properties after internal fixation of osteochondral
      fractures. Type of Study: Cohort study. METHODS: The general principle of
      management of detached acute osteochondral fractures is reattachment of the
      fragment by internal fixation, but the opinions on the quality and structure of
      the healed tissue that will be obtained after treatment is controversial. This
      study included 13 patients with acute osteochondral fractures who were treated
      arthroscopically and had surgical fixation providing joint-surface congruity.
      Patients with osteochondral fractures too small for fixation or with the
      overlying cartilage frayed, and patients with associated injuries were excluded
      from the study. The mean age of patients was 17 years (9 to 24 years). In 2 cases
      the fractures were localized at medial, in 7 at lateral femoral condyles, and in
      4 at the patella. Internal fixation materials were K-wires for 1 case, Herbert
      screws for 3, and mini cancellous screws for 9 cases. The mean follow-up period
      was 6.3 years (3 to 13 years). On second-look arthroscopy, congruity of the joint
      surfaces and healed fractures was observed in all cases. Beside removal of the
      implant, punch biopsies were performed extending to the osteochondral junction;
      biopsy specimens were taken from the junction of the articular margin of the
      fragment and the edge of the remainder of the articular surface. RESULTS: On
      histologic examination of the specimens, scarce mature chondrocytes among
      regenerative stroma, which dyed more eosinophilic than the basophilic chondral
      stroma and which had a chondrocyte-like appearance, were seen. Maturation of
      histologic architecture to hyaline or articular cartilage was not recorded in any
      of these cases. CONCLUSIONS: The clinical results did not correlate with the
      histologic findings. Despite the protected joint surface congruence, restoration
      of the hyaline cartilage at the chondral junctions could not be obtained.

PMID- 11239350
TI  - Evaluation of arthroscopic articular cartilage biopsy for osteoarthritis of the
      knee.
AB  - PURPOSE: Arthroscopic evaluation of the articular surface by visualization and
      palpation has proved to be unreliable; therefore, we investigated
      arthroscopically procured biopsy specimens and conventional sections by using the
      same histopathomorphologic techniques and compared the results for possible
      differences. METHODS: Cartilage biopsy specimens of 1.7 mm in diameter and
      conventional cartilage sections (pieces of 8 x 2 mm) were removed from the
      lateral femoral condyle of 53 osteoarthritis patients undergoing total knee
      arthroplasty. Biopsies and conventional sections were evaluated histologically by
      using Mankin's grading system and immunohistochemically by assessing the
      immunoreactivity of the chondrocytes to MMP-1 and MMP-3. RESULTS: The comparison
      between the biopsies and conventional sections revealed that there were no
      differences between these forms of obtaining specimens. Moreover, the expression
      of MMP-1 and MMP-3 in biopsy specimens showed a strong correlation with that in
      conventional sections. CONCLUSIONS: We conclude that in small biopsy specimens
      taken (e.g., during arthoscopy), the histological grading of osteoarthritis
      severity and the evaluation of MMP expression yield results similar to those
      obtained in conventional sections.

PMID- 11239351
TI  - Arthroscopic surgery for septic arthritis of the hip joint in 4 adults.
AB  - PURPOSE: Arthroscopic surgery for septic coxarthritis has not become a well
      established technique despite its minimally invasive nature. The authors
      performed arthroscopic surgery and intraoperative high-volume irrigation on 4
      adult patients with septic coxarthritis. This minimally invasive procedure was
      successful in treating these patients, and there was no recurrence of arthritis
      or other complications. The purpose of this article is to introduce this 3
      directional-approach method of arthroscopic surgery for septic coxarthritis. Type
      of Study: Case study of arthroscopic surgery for septic arthritis of the hip
      joint in 4 adults. METHODS: There were 3 women and 1 man with an average age of
      58 years. The length of time from onset of symptoms to surgery averaged 36 days.
      One patient had diabetes; another had subarachnoid hemorrhage and was being
      treated with steroidal drugs. The etiologic agent was found to be Staphylococcus
      aureus infection in 2 patients, Serratia sp. in 1 patient, and group-B
      Streptococcus in 1 patient. Three-directional-approach arthroscopic surgery and
      intraoperative high-volume irrigation were performed using 20 to 25 L of
      physiologic saline on the 4 patients. Continuous postoperative intra-articular
      irrigation was not performed. RESULTS: Inflammatory reactions subsided within 4
      weeks of surgery in 3 of the 4 patients and within 6 weeks in the other patient.
      At the time of the final examination, the postoperative follow-up period ranged
      from 1 to 6 years and none of the patients had ankylosis of the hip joint.
      CONCLUSIONS: Three-directional-approach arthroscopic surgery in combination with
      intraoperative large-volume irrigation is an effective technique for treating
      septic arthritis of the hip joint because the joint can be preserved and it is
      less invasive than other open arthrotomy techniques.

PMID- 11239352
TI  - Results of medial patellofemoral ligament reconstruction in the treatment of
      patellar dislocation.
AB  - PURPOSE: The purpose of this study is to describe the technique of medial
      patellofemoral ligament reconstruction using autogenous hamstrings or autogenous
      fascia lata and report the results at a minimum 2-year follow-up. Type of Study:
      This study represents a case series. Patients with patellofemoral instability
      following patellar dislocation were restrospectively reviewed after being treated
      with medial patellofemoral ligament reconstruction. No concurrent control group
      was used. METHODS: Nineteen consecutive patients underwent medial patellofemoral
      repair or reconstruction in the treatment of patellar instability after patellar
      dislocation. The reconstructions were performed using autogenous gracilis and/or
      semitendinosus tendons or a strip of autogenous fascia lata. Fifteen patients
      were available for interview, examination, and radiographic evaluation, with a
      mean follow-up of 31.5 months. RESULTS: Subjectively, 10 knees had excellent
      results, 3 knees obtained good results, 1 knee had a fair result, and 1 knee had
      a poor result, for a total of 93% improvement overall. Using Fulkerson's
      functional knee score, 93% had good or excellent results. The average
      postoperative result on Kujala's score for anterior knee symptoms was 88 (range,
      80-100). The Tegner activity level averaged 6.8 preinjury and 6.7
      postoperatively. Radiographic evaluation showed significant improvements in the
      congruence angle by an average of 20 degrees (P =.0006), and in the lateral
      patellofemoral angle by an average of 10 degrees (P =.0003). CONCLUSIONS:
      Surgical reconstruction or repair of the medial patellofemoral ligament provides
      favorable results for the treatment of recurrent patellofemoral dislocations with
      regard to radiographic findings, patient satisfaction, and functional outcome.

PMID- 11239353
TI  - Poor correlation of clinical signs with patellar cartilaginous changes.
AB  - PURPOSE: There is controversy between the symptoms and signs of chondromalacia.
      Patellar chondromalacia has several clinical tests, whose reliability as a
      parameter of chondral damage is unclear. The purpose of this prospective study
      was to correlate the sensitivity, specificity, predictive values and accuracy of
      clinical patellar tests with the findings at arthroscopy. Type of Study: In this
      prospective study, 100 consecutive knees that were subjected to arthroscopy were
      examined. METHODS: Because of missing data, 85 of the 100 knees were included in
      the final analysis. There were 41 male and 44 female patients with an average age
      of 39 and 44 years, respectively. The clinical tests were the tracking test, the
      apprehension test, the patellar inhibition test, and the flexion test. These
      tests were compared with the arthroscopic findings of the patellar cartilage. The
      classification of Outerbridge was used for evaluation of the condition of the
      patellar cartilage. RESULTS: At arthroscopy, there were no patellar cartilage
      changes in 33 knees. Patellar chondromalacia was seen in 52 knees. Grade I
      changes were found in 9 knees, grade II in 21 knees, grade III in 17 knees, and
      grade IV in 5 knees. Among the 4 clinical tests, the sensitivity was best for the
      tracking test (56%). The flexion test had the greatest specificity (85%), but a
      low sensitivity (35%). None of the tests showed acceptable results in terms of
      both sensitivity and specificity. The predictive values and the accuracy of a
      test were low, too. CONCLUSIONS: The sensitivity and specificity, predictive
      values, and accuracy of a test were generally low, except perhaps the specificity
      of the flexion test. The current clinical tests seem to have little value as
      indicators of patellar chondral pathology.

PMID- 11239354
TI  - Inhibiting the inflammatory response in joint sepsis.
AB  - PURPOSE: We created a rabbit model of infectious arthritis to test the effects of
      WRC-0470 (2-cyclohexylmethylidenehydarazinoadenosine), an adenosine analogue, and
      rolipram, a type IV phosphodiesterase inhibitor, on intra-articular white blood
      cell recruitment. Type of Study: Randomized trial involving mature rabbits.
      METHODS: Intra-articular injections ranging from 0 to 2,000 ng of Escherichia
      coli lipopolysaccharide (LPS) were tested as the infectious stimulus. The optimal
      LPS amount was determined based on synovial fluid analysis for white blood cell
      counts. A separate cohort of rabbits then received various intravenous
      concentrations of either rolipram, WRC-0470, or a combination of the 2
      medications. Synovial fluid aspirations after a 6-hour incubation were analyzed
      for white blood cell counts. RESULTS: Intra-articular injections of 200 ng of LPS
      reproducibly generated an inflammatory response of 4,000 cells/mL of synovial
      fluid, establishing the use of this dose of LPS for our septic arthritis model.
      Following infusions of 10 ug/kg/min, the average white blood cell count dropped
      to 800 cells/mL for WRC-0470 (P <.01) and 1,225 cells/mL for rolipram (P <.05). A
      synergistic effect was seen with the combination of both medications at just 1.0
      ug/kg/min, with a mean white blood cell count of 1,090 cells/mL (P <.01).
      CONCLUSIONS: Septic arthritis is a common clinical entity that frequently results
      in major long-term morbidity. Although bacteria can directly damage the articular
      surface, the cytokine-mediated immune response to the infection can exacerbate
      the insult by promoting the release of proteolytic enzymes by white blood cells.
      Currently, no established intervention exists that will decrease the inflammatory
      response to infectious challenges. Our study shows that WRC-0470 and rolipram
      effectively reduce the intra-articular recruitment of white blood cells in a
      septic arthritis model. Future investigations of these drugs will determine their
      ultimate degree of efficacy at limiting the joint destruction associated with
      septic arthritis.

PMID- 11239355
TI  - Irreducible knee dislocation treated by arthroscopic debridement.
AB  - This case report introduces arthroscopic debridement as a new method of treating
      an irreducible knee dislocation. The clinical presentation of 2 patients with
      irreducible knee dislocations, including history, physical examination, a
      clinical photograph, radiographs, and magnetic resonance images, is presented. As
      well, intraoperative arthroscopic photographs are included that show the
      effectiveness of the treatment. A review of the literature reveals that
      irreducible knee dislocations are rare. The finding of a skin furrow along the
      joint line was present in all cases. Past treatment usually involved an open
      procedure to remove the capsuloligamentous structures from the joint. We show
      that arthroscopy with debridement of these structures resulted in reduction of
      the joint. Follow-up arthroscopy in 1 patient showed healing of the previously
      debrided ligament. The ability to debride the interposed soft tissue through the
      arthroscope allows for reduction of the joint without the need for an open
      procedure.

PMID- 11239356
TI  - Arthroscopic treatment of tumor-like lesions of the knee joint: Localized
      pigmented villonodular synovitis and ganglion cyst of the anterior cruciate
      ligament.
AB  - We present the arthroscopic treatment of a case of localized pigmented
      villonodular synovitis that led to increasing restriction of knee flexion and the
      case of a ganglion cyst within the anterior cruciate ligament causing unspecific
      pain. Both pathologies could be resected arthroscopically with complete relief of
      symptoms and no recurrence. In cases with unspecific clinical signs and intra
      articular masses shown on magnetic resonance imaging, arthroscopy is the next
      therapeutic step. Localized tumor-like lesions can often be excised without
      recurrence in the same session.

PMID- 11239357
TI  - Modified cross-pin femoral fixation using long needles, polydioxanone suture, and
      traction suture for hamstring anterior cruciate ligament reconstruction.
AB  - The use of cross-pin femoral fixation in anterior cruciate ligament (ACL)
      reconstruction using semitendinosus and gracilis (ST/G) tendons has been shown to
      be biomechanically sound. As a result of some technical problems that we
      encountered, we modified the technique of the DePuy OrthoTech Xact ACL Graft
      Fixation System (DePuy, Warsaw, IN) using No. 2/0 polydioxanone suture (PDS) with
      long needles normally used for inside-out meniscal repair. In addition, a No. 5
      Ethibond suture loop (Ethicon, Somerville, NJ) is used for traction of the ST/G
      graft up the femoral tunnel. Using a 2-suture loops technique, the traction
      suture loop offers a more effective in-line pull for the graft and it pulls the
      ST/G loops slightly higher than the alignment PDS. By so doing, it lessens the
      chance of kinking the alignment guidewire or even amputating the graft. Although
      not reported in literature, this type of graft complication is possible in other
      single-alignment suture or guidewire techniques.

PMID- 11239358
TI  - One-incision endoscopic technique for posterior cruciate ligament reconstruction
      with quadriceps tendon-patellar bone autograft.
AB  - Quadriceps tendon-patellar bone autograft is an alternative graft choice for
      posterior cruciate ligament (PCL) reconstruction. A 2-incision technique with
      outside-in fixation at the femoral condyle is generally used. In this article, we
      describe a 1-incision endoscopic technique for PCL reconstruction with quadriceps
      tendon-patellar bone autograft. The graft consists of a proximal patellar bone
      plug and central quadriceps tendon. The bone plug is trapezoidal, 20 mm long, 10
      mm wide, and 8 mm thick. The tendon portion is 80 mm long, 10 mm wide, and 6 mm
      thick, including the full-thickness of the rectus femoris and partial thickness
      of the vastus intermedius. Three arthroscopic portals, including anteromedial,
      anterolateral, and posteromedial, are used. All procedures are performed in an
      endoscopic manner with only 1 incision at the proximal tibia. At the femoral
      side, the bone plug is fixed by an interference screw. At the tibial side, the
      tendon portion is fixed by a suture to a screw on the anterior cortex and an
      interference bioscrew in the posterior tibial tunnel opening. Quadriceps tendon
      autograft has the advantages of being self-available, allowing for easier
      arthroscopic technique, and providing comparable graft size. The 1-incision
      technique provides a simple reconstruction method for PCL insufficiency without a
      second incision at the medial femoral condyle.

PMID- 11239359
TI  - High portal: Practical philosophy for positioning portals in knee arthroscopy.
AB  - The purpose of this article is to present the suitable location of portals during
      knee arthroscopy in various situations. It includes universal portal, meniscal
      lesions, discoid meniscus, 1-incision technique of posterior and of anterior
      cruciate ligament reconstructions, stiff knee, transseptal posterior portal, and
      far midpatellar portal. These specific descriptions in each situation are drawn
      from the accumulated experience of more than 4,000 cases of arthroscopy. Our
      philosophy on the positioning of knee portals can be emphasized from 2
      perspectives: first, the location of portals should flexibly suit the surgeon's
      need rather than a fixed location; second, the higher the portal position is in
      knee arthroscopy, the wider view it generally provides inside the joint.

PMID- 11239361
TI  - Capsular disruption as a complication of thermal alteration of the glenohumeral
      capsule.
AB  - Thermal energy, delivered through various means, has been used to alter the
      length of collagen in the unstable shoulder. Laboratory studies have shown that
      the collagen, following thermal alteration, has reduced strength. We present a
      case of radiofrequency capsulorrhaphy of the shoulder for symptomatic posterior
      instability in a multidirectionally lax patient that led to early catastrophic
      failure of the capsule, with complete capsular disruption and hyaline
      degeneration of the treated tissue.

PMID- 11239362
TI  - Delayed degradation of bioabsorbable meniscal fixators.
AB  - A greater understanding of the functional importance of the meniscus has prompted
      a more aggressive approach to conserving meniscal tissue. Multiple treatment
      options exist when dealing with a tear of the meniscus. As the popularity of
      bioabsorbable implants in the orthopaedic armamentarium grows, concern exists as
      to the potential associated complications. We describe a case of the failure of a
      bioabsorbable meniscal fixator appropriately applied to a posterior medial
      meniscal tear with an associated injury of the anterior cruciate ligament.
      Moreover, the concern of implant retention secondary to delayed degradation and
      resultant potential for articular cartilage damage was present.

PMID- 11239363
TI  - Technical note: Resterilizable noninvasive ankle distraction device.
AB  - Arthroscopic ankle surgery can be performed effectively and satisfactorily in the
      majority of procedures without distraction. However, there are cases in which
      joint distraction eases access to the pathology and, therefore, improves
      execution of the surgical procedure. We developed a simple resterilizable
      noninvasive distraction device that is cheap, gives reproducible results, and is
      easy to apply. The main advantage of the device is that the choice to perform
      distraction can be made at any moment during the arthroscopic procedure. Thus,
      the operation can start without distraction in the dorsiflexed position and, if
      needed at any time, the distraction device can be applied and vice versa. The
      effectiveness was assessed in a consecutive series of 25 patients. The average
      force of distraction was 115 N, while the average joint distraction was 4.5 mm on
      the medial and 4.3 mm on the lateral side.

PMID- 11239364
TI  - Technical note: The quadrant technique for arthroscopic treatment of rotator cuff
      calcifications.
AB  - Reliable intraoperative localization of the calcium deposit is the most demanding
      and often time-consuming part of arthroscopic surgery for calcifying tendinitis
      of the rotator cuff. A new technique is described to intraoperatively localize
      calcium deposits based on preoperative ultrasonographic identification and
      subsequent assignment to a defined quadrant lateral of the acromion edge. The
      technique requires only a partial subacromial bursectomy, making the procedure
      less invasive and faster to perform.

PMID- 11239365
TI  - Electrical conduits within the inferior atrial region exhibit preferential roles
      in interatrial activation.
AB  - Differences between conduction properties of interatrial conduits and their roles
      in initiation and maintenance of supraventricular arrhythmias remain unclear. Our
      objective was to determine details of interatrial activation in inferior atrial
      region and to correlate intra-atrial and interatrial activation patterns with the
      site of origin of atrial ectopic activation. In 9 dogs, basket-catheters carrying
      64 electrodes were deployed into both the right atrium (RA) and left atrium (LA).
      A 10-electrode catheter was inserted into the coronary sinus (CS). Activation
      patterns of the RA, LA, and CS were compared during pacing in the CS, in RA
      inferoparaseptum posterior to Eustachian ridge-tendon of Todaro (TT), and in
      inferior RA near the CS ostium (anterior to TT). We found that pacing in proximal
      and middle CS resulted in a RA breakthrough invariably at the CS ostium,
      consistent with conduction through a CS-RA connection. Meanwhile, LA breakthrough
      emerged in inferoposterior region (inferior to mitral annulus), suggesting
      conduction through a CS-LA connection. While pacing in distal CS, LA breakthrough
      shifted to middle posterolateral wall. Whereas, the RA was activated by the LA
      directly through the septum. During pacing in RA inferoparaseptum posterior to
      TT, the LA was activated directly through the septum at 22 +/- 4 ms. Whereas,
      during pacing anterior to TT, the LA was activated through both the CS and the
      septum while earliest activation was delayed by 38 +/- 5 ms. In conclusion, both
      the interatrial septum and CS musculature form electrical conduits in inferior
      atrial region in canine. Differences in activation properties between the
      conduits in inferior interatrial region result in selective interatrial
      activation patterns during ectopic activation.

PMID- 11239366
TI  - Spectral analysis of epicardial 60-lead electrograms in dogs with 4-week-old
      myocardial infarction.
AB  - There were few studies on the spectral analysis of multiple-lead epicardial
      electrograms in chronic myocardial infarction. Spectral analysis of multi-lead
      epicardial electrograms was performed in 6 sham-operated dogs (N group) and 8
      dogs with 4-week-old myocardial infarction (MI group). Four weeks after the
      ligation of left anterior descending coronary artery, fast Fourier transform was
      performed on 60-lead epicardial electrograms, and then inverse transform was
      performed on 5 frequency ranges from 0 to 250 Hz. From the QRS onset to QRS
      offset, the time integration of unsigned value of reconstructed waveform was
      calculated and displayed as AQRS maps. On 0-25 Hz AQRS map, there was no
      significant difference between the 2 groups. In the frequency ranges of 25-250
      Hz, MI group had significantly smaller AQRS values than N group solely in the
      infarct zone. It was shown that high frequency potentials (25-250 Hz) within QRS
      complex were reduced in the infarct zone.

PMID- 11239367
TI  - A placebo controlled evaluation of the antifibrillatory effects of carvedilol.
AB  - This article evaluates the antifibrillatory effects of carvedilol 5 mg/kg and
      vehicle (dimethyl-formamide) over time. Sprague-Dawley rats were anesthetized and
      intubated. They underwent baseline ventricular fibrillation threshold (VFT)
      determination and then received 1 of the 2 treatments (n = 10/group) over 8
      minutes. VFT and determinations were performed at 2, 7, 15, 30, 45, and 60
      minutes postinfusion. Carvedilol significantly increased the VFT at 2, 7, 15, 30
      minutes versus baseline and the vehicle control group. Carvedilol significantly
      reduced the heart rate and the mean arterial pressure at every evaluable time
      point versus baseline and vehicle control. Carvedilol showed significant
      antifibrillatory effects versus baseline and vehicle for the first 30 minutes but
      not thereafter, even though the heart rate and mean arterial pressure remain
      significantly reduced.

PMID- 11239368
TI  - Paradoxical behavior of PR interval dynamics during exercise and recovery and its
      relationship to cardiac memory at the atrioventricular node.
AB  - This preliminary study deals with the dynamics of the PR interval during exercise
      testing by using a Bruce protocol in 31 nonmedicated, normal patients with ages
      of 33 +/- 14 years. The behavior of the PR interval permitted its categorization
      into 2 groups. In Group I (27 of 31, 87.1% of patients) the PR interval showed
      the expected biphasic behavior with a gradual shortening with increasing exercise
      and a gradual lengthening during recovery. In contrast, the PR interval in Group
      II (4 of 31, 12.9% of patients) showed a triphasic behavior since, toward the end
      of recovery, there was a second decrease in duration. Because of this temporal
      relation to the phases of exercise, this paradoxical response, in analogy to what
      happened to the QT interval during exercise, could have been caused by a form of
      short-term memory or to varying, but normal, intergroup differences in autonomic
      function. However, further studies involving a greater number of patients are
      required to reach definite conclusions.

PMID- 11239369
TI  - Autonomic influences on ventricular repolarization in congestive heart failure.
AB  - We studied the QT interval rate-dependence in patients with congestive heart
      failure (CHF). The long-term autonomic nervous function was investigated by
      separate analysis of diurnal and nocturnal periods. For this purpose, QTm rate
      dependence was determined from Holter recordings. Twelve patients with stable CHF
      (mean age 63 +/- 2 years) and 15 healthy subjects (mean age 59 +/- 4 years) were
      included in the study. CHF patients showed an increased nocturnal QTm rate
      dependence when compared to normal subjects (0.150 [95% confidence interval (CI)
      0.114 to 0.186] versus 0.106 [95% CI 0.080 to 0.133], P < .05). In contrast, QTm
      rate-dependence was not significantly different between the 2 groups during the
      day (0.177 [95% CI 0.149 to 0.210] in the CHF group versus 0.194 [95% CI 0.158 to
      0.231] in the control group). It was also not significantly different between day
      and night for the CHF group, thus showing a loss of the circadian modulation in
      these patients. Thus, ventricular myocardial properties are altered by changes in
      the autonomic nervous system in CHF, as observed at the atrial level. These
      modifications may be related to the increased susceptibility to ventricular
      arrhythmias.

PMID- 11239370
TI  - Standards for the function of an academic 12-lead electrocardiographic core
      laboratory.
AB  - An academic 12-lead electrocardiogram (ECG) core laboratory aims to provide the
      highest possible quality ECG recording, measurement, and storage to aid
      clinicians in research into important cardiovascular outcomes and to maximize the
      credibility of scientific results based solely, or in part, on ECG data. This
      position paper presents a guide for the structure and function of an academic ECG
      core laboratory. The key functional aspects are: 1) Data collection, 2) Staff
      composition, 3) Diagnostic measurement and definition standards, 4) Data
      management, 5) Academic considerations, 6) Economic consideration, and 7)
      Accreditation. An ECG Core Laboratory has the responsibility for rapid and
      accurate analysis and responsible management of the electrocardiographic data in
      multicenter clinical trials. Academic Laboratories, in addition, provide
      leadership in research protocol generation and production of research manuscripts
      for submission to the appropriate peer-review journals.

PMID- 11239371
TI  - Prevention of atrial fibrillation by multisite atrial pacing.

PMID- 11239372
TI  - Patterns of acute inferior wall myocardial infarction caused by hyperkalemia.
AB  - This is one of the first published articles dealing with two patients with
      hyperkalemia showing, not only a pattern of acute anteroseptal myocardial
      infarction, but of inferior myocardial infarction as well. This was attributed to
      uneven effects of high potassium in different regions of the heart. Marked
      reduction of resting potential of a large group of cells from the most affected
      regions could produce areas of inexcitability, capable of generating abnormal q
      waves. Likewise, ST-segment elevation could be attributed to a hyperkalemic
      diastolic current of injury (due to depolarization of resting potential) and to a
      combination of diastolic and systolic current of injury (due to a reduction of
      action potential amplitude). In addition, current flowing down voltage gradients
      on either side (epicardial and endocardial) of the M cell region could be
      responsible for the T wave, and even, to some extent, to the ST-segment changes.
      However, it cannot be excluded that the previously described changes may have
      resulted from coronary spasm without chest pain. In fact, an intriguing
      possibility, namely that hyperkalemia could trigger coronary spasm has to be
      considered also.

PMID- 11239373
TI  - Double ventricular response via dual atrioventricular nodal pathways resulting
      with nonreentrant supraventricular tachycardia and successfully treated with
      radiofrequency catheter ablation.
AB  - We report a patient with a complex nonreentrant supraventricular tachycardia
      because of double ventricular response resulting from antegrade dual
      atrioventricular (AV) nodal pathways. We could induce double ventricular response
      and confirm dual AV nodal pathways by AV simultaneous pacing during basic
      stimulation proceeding with programmed atrial single extrastimulation. As far as
      we know, it is the first report about the application of the AV simultaneous
      basic stimulation to prove the sustained nonreentrant tachycardia because of
      simultaneous conduction over dual AV nodal pathways. This was also confirmed by
      absence of the arrhythmia immediately after the elimination of the slow pathway
      conduction by radiofrequency ablation.

PMID- 11239374
TI  - Syncope in patients with atrial flutter during treatment with class Ic
      antiarrhythmic drugs.
AB  - We describe 2 atrial flutter (AFL) patients with syncope during treatment with
      class Ic antiarrhythmic drugs. During the syncope, 1:1 atrioventricular (AV)
      conduction during AFL preceded a wide QRS tachycardia. The class Ic drugs,
      flecainide and pilsicainide, slowed the atrial rate, resulting in AFL with 1:1 AV
      conduction, and the width of the QRS complexes became wider during the
      tachycardia. Syncope was abolished after successful radiofrequency catheter
      ablation of the AFL. These potential proarrhythmic effects of the class Ic drugs
      should be taken into account in AFL patients, and concomitant use of beta
      blocking agents would be critical to prevent proarrhythmias.

PMID- 11239375
TI  - Mental stress-induced myocardial ischemia in association with a myocardial
      bridge.

PMID- 11239376
TI  - Reverse use-dependent QT prolongation during infusion of nifekalant in a case of
      recurrent ventricular tachycardia with old myocardial infarction.
AB  - Pure class III antiarrhythmic agents cause reverse use-dependent QT prolongation.
      Nifekalant is a new class III antiarrhythmic agent and blocks rapid component of
      the delayed rectifier K+ current (Ikr) selectively. To prevent recurrent
      ventricular tachycardia in a patient with old myocardial infarction, nifekalant
      was administered by continuous intravenous infusion. There was little variation
      in the blood level of nifekalant during the 1-day period, but the QTc interval
      became shorter with an increase of the heart rate early in the morning. It is
      therefore considered advisable to monitor the heart rate and QTc interval during
      administration of nifekalant by continuous intravenous infusion.

PMID- 11239377
TI  - Apparent bradycardia-dependent right bundle branch block associated with atrial
      fibrillation: concealed electrotonic conduction as a possible mechanism.
AB  - A 79-year-old woman with atrial fibrillation was reported in whom apparent
      bradycardia-dependent right bundle branch block was suggested. When a conducted
      supraventricular impulse occurred within a critical period after the preceding
      conducted impulse, the impulse was blocked in the right bundle branch except when
      it fell in the supernormal period of the right bundle branch. When the conducted
      impulse occurred between the critical period and another longer period, it was
      conducted without bundle branch block. When the impulse occurred beyond that
      longer period, it was usually blocked in the bundle branch again. However, when
      the impulse occurred beyond a still longer period, it was conducted without
      bundle branch block again. These findings suggest that when impulses fell in the
      right bundle branch shortly after the preceding conducted impulses, they were
      blocked in both bundle branches; however, it seemed that concealed electrotonic
      conduction of the blocked impulses affected conduction of the subsequent
      impulses.

PMID- 11239378
TI  - Strategies for the economic survival of vascular surgeons: an overview.

PMID- 11239379
TI  - Key success factors in a vascular surgery practice.
AB  - The practice of medicine is becoming more complex. Physicians need to rely on
      others or to change their focus to include business management. Key success
      factors exist that may be used by the vascular surgeon to develop a paradigm
      appropriate for the business side of the practice. These factors include a
      vision, a systematic approach, teamwork, communications, time management,
      marketing, financial analysis, and to be innovative in business matters. The
      reader should be able to review their practice and implement the various
      activities discussed to achieve overall efficiency and effectiveness in the
      business aspect and the practice of vascular surgery.

PMID- 11239380
TI  - Development and utilization of paperless medical records: a unique approach.
AB  - The purpose of this article is to describe the development and utilization of a
      unique paperless medical record system in a large multispeciality group practice
      setting. The Scott and White integrated health care delivery system provides care
      over a 34-county area in Central Texas. Since 1988, clinicians at Scott and White
      have developed a text-based, content-searchable electronic medical record system
      known as EMRx. This system provides a single clinical data repository that allows
      patient care activities and aggregate data analyses to occur by using the same
      set of data on a daily basis. Use of this approach has led to the aggregation of
      over 9.8 million clinical documents since 1994. Over 1,845 health care providers
      used the system during May 2000 for direct patient care; 866,114 patient records
      have been accessed since January 1, 1999 to answer questions related to patient
      care, quality assurance, outcomes research, and accreditation.

PMID- 11239381
TI  - Cost-effectiveness and cost-efficiency in vascular surgery.
AB  - Medical costs have been an increasing focus of attention in medicine in general,
      particularly in the United States health care environment. Because vascular
      disease is most prevalent in the elderly, the forecasted growth of this
      population over the next several decades will put increasing strains on health
      care financing. Costs will undoubtedly be a major component of any system of
      outcomes measurement, and it is important for vascular surgeons and others who
      specialize in vascular disease to be familiar with the definitions and
      methodology and cost-effectiveness analysis. Similarly, improving cost efficiency
      within the practice of vascular surgery will be mandated. The purpose of this
      article is to review systems of cost-effectiveness analysis as they pertain to
      vascular surgery, as well as to define critical pathway models that have been
      used to improve cost-efficiency in vascular surgery.

PMID- 11239382
TI  - Determination and importance of clinical and patient-based measures in outcome
      assessment of peripheral arterial occlusive disease.
AB  - Therapeutic effectiveness is the overall effect of an intervention on clinical
      and quality-of-life measures. Traditionally, in peripheral arterial disease, this
      has been evaluated in terms of clinical outcomes only. The lack of correlation
      between quality-of-life and clinical measures means that these cannot adequately
      describe overall patient benefit or adverse effects from an intervention.
      Therefore, patient-based measures such as changes in disease-specific
      questionnaire scores must be included in the evaluation of therapeutic
      effectiveness.

PMID- 11239383
TI  - The use of a resource-based relative value scale (RBRVS) to determine practice
      expense costs: a novel technique of practice management for the vascular surgeon.
AB  - Vascular surgeons have had to contend with rising costs while their
      reimbursements have undergone steady reductions. The use of newer accounting
      techniques can help vascular surgeons better manage their practices, plan for
      future expansion, and control costs. This article reviews traditional accounting
      methods, together with activity-based costing (ABC) principles that have been
      used in the past for practice expense analysis. The main focus is on a new
      technique-resource-based costing (RBC)-which uses the widely available Resource
      Based Relative Value Scale (RBRVS) as its basis. The RBC technique promises
      easier implementation as well as more flexibility in determining true costs of
      performing various procedures, as opposed to more traditional accounting methods.
      It is hoped that RBC will assist vascular surgeons in coping with decreasing
      reimbursement.

PMID- 11239384
TI  - Income statement management in a turbulent health care environment.
AB  - This article considers the role of accounting information embedded in the income
      statement of health care providers in their increasingly difficult economic
      environment. This turbulent economic environment has resulted from the dramatic
      shift in power from the seller to the buyer of health care services, with a
      consequential shift of risks that will mandate that health care providers obtain
      access to better cost and utilization information. This article looks at the 2
      critical components of the income statement--the revenue function and the cost
      structure-in terms of their importance in the management of enhanced economic
      performance in both the fee-for-service and the prepaid provision of health care
      services.

PMID- 11239385
TI  - Regulation of vascular surgery by the federal government.
AB  - Governmental regulation of medicine seeks to protect patients and employees
      providing health care and to insure fair reimbursement for services. This report
      outlines workplace regulation of bloodborne pathogens and ergonomics. The
      investigation of potential Medicare fraud and abuse is reviewed. Mechanisms that
      control physician payment policy, including the Relative Base Resource Value
      System, the Correct Coding Initiative, and Current Procedural Terminology, are
      described.

PMID- 11239386
TI  - Predicting the future of vascular health care: the impact of the baby boom
      generation.
AB  - With the aging of the "Baby Boomers," the need for vascular care will be
      substantial. Three things predominate: (1) variability in distribution of the
      work force, (2) increasing use of all vascular procedures, and (3) marked
      geographic variation as to who receives vascular therapy. The mandate to
      standardize therapy with the least resource utilization and the best results will
      only strengthen with time.

PMID- 11239387
TI  - The multidisciplinary approach to prevention and treatment of cardiovascular
      disease: creation of a vascular care network.
AB  - Vascular care, diagnosis, and intervention can be very complex. Multiple
      specialists commonly are involved in dealing with patients with systemic
      atherosclerotic disease. Although each specialist may provide state-of-the-art
      care with good result, it would be advantageous to minimize duplication of effort
      and thereby improve cost efficiency. Patients still could reap the benefit of all
      these disciplines if evaluated for their vascular complaint in a coordinated
      system. In doing so, atherosclerosis prevention with risk factor modification, as
      well as diagnosis and therapy for the presenting problem all can be
      simultaneously managed. This is the concept that has motivated groups such as our
      own to form a comprehensive vascular center. We describe our experience with
      establishing a vascular center and outline its benefits and limitations.

PMID- 11239388
TI  - Running on Ran: nuclear transport and the mitotic spindle.

PMID- 11239389
TI  - Apoptosis: corralling the corpses.

PMID- 11239390
TI  - Spontaneous DNA damage, genome instability, and cancer--when DNA replication
      escapes control.

PMID- 11239391
TI  - A biological atlas of functional maps.

PMID- 11239392
TI  - Wnt-14 plays a pivotal role in inducing synovial joint formation in the
      developing appendicular skeleton.
AB  - The long bones of the vertebrate appendicular skeleton arise from initially
      continuous condensations of mesenchymal cells that subsequently segment and
      cavitate to form discrete elements separated by synovial joints. Little is known,
      however, about the molecular mechanisms of joint formation. We present evidence
      that Wnt-14 plays a central role in initiating synovial joint formation in the
      chick limb. Wnt-14 is expressed in joint-forming regions prior to the
      segmentation of the cartilage elements, and local misexpression of Wnt-14 induces
      morphological and molecular changes characteristic of the first steps of joint
      formation. Induction of an ectopic joint-like region by Wnt-14 suppresses the
      formation of the immediately adjacent endogenous joint, potentially providing
      insight into the spacing of joints.

PMID- 11239393
TI  - Defective interplay of activators and repressors with TFIH in xeroderma
      pigmentosum.
AB  - Inherited mutations of the TFIIH helicase subunits xeroderma pigmentosum (XP) B
      or XPD yield overlapping DNA repair and transcription syndromes. The high risk of
      cancer in these patients is not fully explained by the repair defect. The
      transcription defect is subtle and has proven more difficult to evaluate. Here,
      XPB and XPD mutations are shown to block transcription activation by the FUSE
      Binding Protein (FBP), a regulator of c-myc expression, and repression by the FBP
      Interacting Repressor (FIR). Through TFIIH, FBP facilitates transcription until
      promoter escape, whereas after initiation, FIR uses TFIIH to delay promoter
      escape. Mutations in TFIIH that impair regulation by FBP and FIR affect proper
      regulation of c-myc expression and have implications in the development of
      malignancy.

PMID- 11239394
TI  - Neurogenin promotes neurogenesis and inhibits glial differentiation by
      independent mechanisms.
AB  - The mechanisms by which neural stem cells give rise to neurons, astrocytes, or
      oligodendrocytes are beginning to be elucidated. However, it is not known how the
      specification of one cell lineage results in the suppression of alternative
      fates. We find that in addition to inducing neurogenesis, the bHLH transcription
      factor neurogenin (Ngn1) inhibits the differentiation of neural stem cells into
      astrocytes. While Ngn1 promotes neurogenesis by functioning as a transcriptional
      activator, Ngn1 inhibits astrocyte differentiation by sequestering the CBP-Smad1
      transcription complex away from astrocyte differentiation genes, and by
      inhibiting the activation of STAT transcription factors that are necessary for
      gliogenesis. Thus, two distinct mechanisms are involved in the activation and
      suppression of gene expression during cell-fate specification by neurogenin.

PMID- 11239395
TI  - The transcription factor associated Ccr4 and Caf1 proteins are components of the
      major cytoplasmic mRNA deadenylase in Saccharomyces cerevisiae.
AB  - The major pathways of mRNA turnover in eukaryotes initiate with shortening of the
      poly(A) tail. We demonstrate by several criteria that CCR4 and CAF1 encode
      critical components of the major cytoplasmic deadenylase in yeast. First, both
      Ccr4p and Caf1p are required for normal mRNA deadenylation in vivo. Second, both
      proteins localize to the cytoplasm. Third, purification of Caf1p copurifies with
      a Ccr4p-dependent poly(A)-specific exonuclease activity. We also provide evidence
      that the Pan2p/Pan3p nuclease complex encodes the predominant alternative
      deadenylase. These results, and previous work on Pan2p/Pan3p, define the mRNA
      deadenylases in yeast. The strong conservation of Ccr4p, Caf1p, Pan2p, and Pan3p
      indicates that they will function as deadenylases in other eukaryotes.
      Interestingly, because Ccr4p and Caf1p interact with transcription factors, these
      results suggest an unexpected link between mRNA synthesis and turnover.

PMID- 11239396
TI  - Cdc13 delivers separate complexes to the telomere for end protection and
      replication.
AB  - In Saccharomyces cerevisiae, the telomere binding protein Cdc13 mediates telomere
      replication by recruiting telomerase, and also performs an essential function in
      chromosome end protection. We show here that delivery of the Stn1 protein to the
      telomere, by fusing the DNA binding domain of Cdc13 (DBD(CDC13)) to Stn1, is
      sufficient to rescue the lethality of a cdc13 null strain and, hence, provide end
      protection. Telomere replication is still defective in this strain, but can be
      restored by delivering telomerase to the telomere as a DBD(CDC13)-telomerase
      fusion. These results establish Stn1 as the primary effector of chromosome end
      protection, whereas the principal function of Cdc13 is to provide a loading
      platform to recruit complexes that provide end protection and telomere
      replication.

PMID- 11239397
TI  - Suppression of spontaneous chromosomal rearrangements by S phase checkpoint
      functions in Saccharomyces cerevisiae.
AB  - Cancer cells show increased genome rearrangements, although it is unclear what
      defects cause these rearrangements. Mutations in Saccharomyces cerevisiae RFC5,
      DPB11, MEC1, DDC2 MEC3, RAD53, CHK1, PDS1, and DUN1 increased the rate of genome
      rearrangements up to 200-fold whereas mutations in RAD9, RAD17, RAD24, BUB3, and
      MAD3 had little effect. The rearrangements were primarily deletion of a portion
      of a chromosome arm along with TEL1-dependent addition of a new telomere. tel1
      mutations increased the proportion of translocations observed, and in some cases
      showed synergistic interactions when combined with mutations that increased the
      genome rearrangement rate. These data suggest that one role of S phase checkpoint
      functions in normal cells is to suppress spontaneous genome rearrangements
      resulting from DNA replication errors.

PMID- 11239398
TI  - Protein kinase D regulates the fission of cell surface destined transport
      carriers from the trans-Golgi network.
AB  - When a kinase inactive form of Protein Kinase D (PKD-K618N) was expressed in HeLa
      cells, it localized to the trans-Golgi network (TGN) and caused extensive
      tubulation. Cargo that was destined for the plasma membrane was found in PKD
      K618N-containing tubes but the tubes did not detach from the TGN. As a result,
      the transfer of cargo from TGN to the plasma membrane was inhibited. We have also
      demonstrated the formation and subsequent detachment of cargo-containing tubes
      from the TGN in cells stably expressing low levels of PKD-K618N. Our results
      suggest that PKD regulates the fission from the TGN of transport carriers that
      are en route to the cell surface.

PMID- 11239399
TI  - SNARE complex oligomerization by synaphin/complexin is essential for synaptic
      vesicle exocytosis.
AB  - Synaphin/complexin is a cytosolic protein that preferentially binds to syntaxin
      within the SNARE complex. We find that synaphin promotes SNAREs to form
      precomplexes that oligomerize into higher order structures. A peptide from the
      central, syntaxin binding domain of synaphin competitively inhibits these two
      proteins from interacting and prevents SNARE complexes from oligomerizing.
      Injection of this peptide into squid giant presynaptic terminals inhibited
      neurotransmitter release at a late prefusion step of synaptic vesicle exocytosis.
      We propose that oligomerization of SNARE complexes into a higher order structure
      creates a SNARE scaffold for efficient, regulated fusion of synaptic vesicles.

PMID- 11239400
TI  - A novel all helix fold of the AP180 amino-terminal domain for phosphoinositide
      binding and clathrin assembly in synaptic vesicle endocytosis.
AB  - Clathrin-mediated endocytosis plays a major role in retrieving synaptic vesicles
      from the plasma membrane following exocytosis. This endocytic process requires
      AP180 (or a homolog), which promotes the assembly and restricts the size of
      clathrin-coated vesicles. The highly conserved 33 kDa amino-terminal domain of
      AP180 plays a critical role in binding to phosphoinositides and in regulating the
      clathrin assembly activity of AP180. The crystal structure of the amino-terminal
      domain reported herein reveals a novel fold consisting of a large double layer of
      sheets of ten alpha helices and a unique site for binding phosphoinositides. The
      finding that the clathrin-box motif is mostly buried and lies in a helix
      indicates a different site and mechanism for binding of the domain to clathrins
      than previously assumed.

PMID- 11239401
TI  - Junction adhesion molecule is a receptor for reovirus.
AB  - Virus attachment to cells plays an essential role in viral tropism and disease.
      Reovirus serotypes 1 and 3 differ in the capacity to target distinct cell types
      in the murine nervous system and in the efficiency to induce apoptosis. The
      binding of viral attachment protein sigma1 to unidentified receptors controls
      these phenotypes. We used expression cloning to identify junction adhesion
      molecule (JAM), an integral tight junction protein, as a reovirus receptor. JAM
      binds directly to sigma1 and permits reovirus infection of nonpermissive cells.
      Ligation of JAM is required for reovirus-induced activation of NF-kappaB and
      apoptosis. Thus, reovirus interaction with cell-surface receptors is a critical
      determinant of both cell-type specific tropism and virus-induced intracellular
      signaling events that culminate in cell death.

PMID- 11239402
TI  - The PAS protein VIVID defines a clock-associated feedback loop that represses
      light input, modulates gating, and regulates clock resetting.
AB  - vvd, a gene regulating light responses in Neurospora, encodes a novel member of
      the PAS/LOV protein superfamily. VVD defines a circadian clock-associated
      autoregulatory feedback loop that influences light resetting, modulates circadian
      gating of input by connecting output and input, and regulates light adaptation.
      Rapidly light induced, vvd is an early repressor of light-regulated processes.
      Further, vvd is clock controlled; the clock gates light induction of vvd and the
      clock gene frq so identical signals yield greater induction in the morning.
      Mutation of vvd severely dampens gating, especially of frq, consistent with VVD
      modulating gating and phasing light-resetting responses. vvd null strains display
      distinct alterations in the phase-response curve to light. Thus VVD, although not
      part of the clock, contributes significantly to regulation within the Neurospora
      circadian system.

PMID- 11239403
TI  - After the genome: DNA and human disease.

PMID- 11239404
TI  - HIV-1 sequence variation: drift, shift, and attenuation.

PMID- 11239405
TI  - New insights into host factors in HIV-1 pathogenesis.

PMID- 11239406
TI  - Microbial pathogenesis of Mycobacterium tuberculosis: dawn of a discipline.

PMID- 11239407
TI  - The TNF and TNF receptor superfamilies: integrating mammalian biology.

PMID- 11239408
TI  - Atherosclerosis. the road ahead.

PMID- 11239409
TI  - New perspectives into the molecular pathogenesis and treatment of type 2
      diabetes.

PMID- 11239410
TI  - Obesity and the regulation of energy balance.

PMID- 11239411
TI  - Molecular mechanisms of human hypertension.

PMID- 11239412
TI  - The genetic basis for cardiomyopathy: from mutation identification to mechanistic
      paradigms.

PMID- 11239413
TI  - Molecular and cellular mechanisms of cardiac arrhythmias.

PMID- 11239414
TI  - Amyotrophic lateral sclerosis. unfolding the toxicity of the misfolded.

PMID- 11239415
TI  - NF1 tumor suppressor gene function: narrowing the GAP.

PMID- 11239416
TI  - Hyperproliferation and defects in epithelial polarity upon conditional ablation
      of alpha-catenin in skin.
AB  - When surface epithelium was conditionally targeted for ablation of alpha-catenin,
      hair follicle development was blocked and epidermal morphogenesis was
      dramatically affected, with defects in adherens junction formation, intercellular
      adhesion, and epithelial polarity. Differentiation occurred, but epidermis
      displayed hyperproliferation, suprabasal mitoses, and multinucleated cells. In
      vitro, alpha-catenin null keratinocytes were poorly contact inhibited and grew
      rapidly. These differences were not dependent upon intercellular adhesion and
      were in marked contrast to keratinocytes conditionally null for another essential
      intercellular adhesion protein, desmoplakin (DP). KO keratinocytes exhibited
      sustained activation of the Ras-MAPK cascade due to aberrations in growth factor
      responses. Thus, remarkably, features of precancerous lesions often attributed to
      defects in cell cycle regulatory genes can be generated by compromising the
      function of alpha-catenin.

PMID- 11239418
TI  - The future of Neuron and the challenges for biomedical research in neuroscience.

PMID- 11239417
TI  - TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge
      syndrome.
AB  - Velo-cardio-facial syndrome (VCFS)/DiGeorge syndrome (DGS) is a human disorder
      characterized by a number of phenotypic features including cardiovascular
      defects. Most VCFS/DGS patients are hemizygous for a 1.5-3.0 Mb region of 22q11.
      To investigate the etiology of this disorder, we used a cre-loxP strategy to
      generate mice that are hemizygous for a 1.5 Mb deletion corresponding to that on
      22q11. These mice exhibit significant perinatal lethality and have conotruncal
      and parathyroid defects. The conotruncal defects can be partially rescued by a
      human BAC containing the TBX1 gene. Mice heterozygous for a null mutation in Tbx1
      develop conotruncal defects. These results together with the expression patterns
      of Tbx1 suggest a major role for this gene in the molecular etiology of VCFS/DGS.

PMID- 11239419
TI  - Tbr1 conducts the orchestration of early cortical development.

PMID- 11239420
TI  - Stimulating new turns.

PMID- 11239421
TI  - CAKbeta/Pyk2 activates Src: another piece in the puzzle of LTP induction.

PMID- 11239422
TI  - Hearing and looking.

PMID- 11239423
TI  - Keeping the wires short: a singularly difficult problem.

PMID- 11239424
TI  - Turning the dial on object perception.

PMID- 11239425
TI  - Spinal motor circuits: merging development and function.

PMID- 11239426
TI  - A genetic analysis of neural progenitor differentiation.
AB  - Genetic mechanisms regulating CNS progenitor function and differentiation are not
      well understood. We have used microarrays derived from a representational
      difference analysis (RDA) subtraction in a heterogeneous stem cell culture system
      to systematically study the gene expression patterns of CNS progenitors. This
      analysis identified both known and novel genes enriched in progenitor cultures.
      In situ hybridization in a subset of clones demonstrated that many of these genes
      were expressed preferentially in germinal zones, some showing distinct
      ventricular or subventricular zone labeling. Several genes were also enriched in
      hematopoietic stem cells, suggesting an overlap of gene expression in neural and
      hematopoietic progenitors. This combination of methods demonstrates the power of
      using custom microarrays derived from RDA-subtracted libraries for both gene
      discovery and gene expression analysis in the central nervous system.

PMID- 11239427
TI  - The nodal pathway acts upstream of hedgehog signaling to specify ventral
      telencephalic identity.
AB  - The Nodal and Hedgehog signaling pathways influence dorsoventral patterning at
      all axial levels of the CNS, but it remains largely unclear how these pathways
      interact to mediate patterning. Here we show that, in zebrafish, Nodal signaling
      is required for induction of the homeobox genes nk2.1a in the ventral
      diencephalon and nk2.1b in the ventral telencephalon. Hedgehog signaling is also
      required for telencephalic nk2.1b expression but may not be essential to
      establish diencephalic nk2.1a expression. Furthermore, Shh does not restore
      ventral diencephalic development in embryos lacking Nodal activity. In contrast,
      Shh does restore telencephalic nk2.1b expression in the absence of Nodal
      activity, suggesting that Hedgehog signaling acts downstream of Nodal activity to
      pattern the ventral telencephalon. Thus, the Nodal pathway regulates ventral
      forebrain patterning through both Hedgehog signaling-dependent and -independent
      mechanisms.

PMID- 11239428
TI  - Tbr1 regulates differentiation of the preplate and layer 6.
AB  - During corticogenesis, early-born neurons of the preplate and layer 6 are
      important for guiding subsequent neuronal migrations and axonal projections. Tbr1
      is a putative transcription factor that is highly expressed in glutamatergic
      early-born cortical neurons. In Tbr1-deficient mice, these early-born neurons had
      molecular and functional defects. Cajal-Retzius cells expressed decreased levels
      of Reelin, resulting in a reeler-like cortical migration disorder. Impaired
      subplate differentiation was associated with ectopic projection of
      thalamocortical fibers into the basal telencephalon. Layer 6 defects contributed
      to errors in the thalamocortical, corticothalamic, and callosal projections.
      These results show that Tbr1 is a common genetic determinant for the
      differentiation of early-born glutamatergic neocortical neurons and provide
      insights into the functions of these neurons as regulators of cortical
      development.

PMID- 11239429
TI  - Control of interneuron fate in the developing spinal cord by the progenitor
      homeodomain protein Dbx1.
AB  - Spinal interneurons help to coordinate motor behavior. During spinal cord
      development, distinct classes of interneurons are generated from progenitor cells
      located at different positions within the ventral neural tube. V0 and V1
      interneurons derive from adjacent progenitor domains that are distinguished by
      expression of the homeodomain proteins Dbx1 and Dbx2. The spatially restricted
      expression of Dbx1 has a critical role in establishing the distinction in V0 and
      V1 neuronal fate. In Dbx1 mutant mice, neural progenitors fail to generate V0
      neurons and instead give rise to interneurons that express many characteristics
      of V1 neurons-their transcription factor profile, neurotransmitter phenotype,
      migratory pattern, and aspects of their axonal trajectory. Thus, a single
      progenitor homeodomain transcription factor coordinates many of the
      differentiated properties of one class of interneurons generated in the ventral
      spinal cord.

PMID- 11239430
TI  - Evx1 is a postmitotic determinant of v0 interneuron identity in the spinal cord.
AB  - Interneurons in the ventral spinal cord are essential for coordinated locomotion
      in vertebrates. During embryogenesis, the V0 and V1 classes of ventral
      interneurons are defined by expression of the homeodomain transcription factors
      Evx1/2 and En1, respectively. In this study, we show that Evx1 V0 interneurons
      are locally projecting intersegmental commissural neurons. In Evx1 mutant
      embryos, the majority of V0 interneurons fail to extend commissural axons.
      Instead, they adopt an En1-like ipsilateral axonal projection and ectopically
      express En1, indicating that V0 interneurons are transfated to a V1 identity.
      Conversely, misexpression of Evx1 represses En1, suggesting that Evx1 may
      suppress the V1 interneuron differentiation program. Our findings demonstrate
      that Evx1 is a postmitotic determinant of V0 interneuron identity and reveal a
      critical postmitotic phase for neuronal determination in the developing spinal
      cord.

PMID- 11239431
TI  - Neural bHLH genes control the neuronal versus glial fate decision in cortical
      progenitors.
AB  - We have addressed the role of the proneural bHLH genes Neurogenin2 (Ngn2) and
      Mash1 in the selection of neuronal and glial fates by neural stem cells. We show
      that mice mutant for both genes present severe defects in development of the
      cerebral cortex, including a reduction of neurogenesis and a premature and
      excessive generation of astrocytic precursors. An analysis of wild-type and
      mutant cortical progenitors in culture showed that a large fraction of Ngn2;
      Mash1 double-mutant progenitors failed to adopt a neuronal fate, instead
      remaining pluripotent or entering an astrocytic differentiation pathway.
      Together, these results demonstrate that proneural genes are involved in lineage
      restriction of cortical progenitors, promoting the acquisition of the neuronal
      fate and inhibiting the astrocytic fate.

PMID- 11239432
TI  - nompA encodes a PNS-specific, ZP domain protein required to connect
      mechanosensory dendrites to sensory structures.
AB  - Mutations in the no-mechanoreceptor-potential A (nompA) gene, which eliminate
      transduction in Drosophila mechanosensory organs, disrupt contacts between
      neuronal sensory endings and cuticular structures. nompA encodes a transmembrane
      protein with a large, modular extracellular segment that includes a zona
      pellucida (ZP) domain and several plasminogen N-terminal (PAN) modules. It is
      specifically expressed in type I sense organs of the peripheral nervous system by
      the support cells that ensheath the neuronal sensory process. A green fluorescent
      protein (GFP)-NompA fusion protein is localized to the dendritic cap, an
      extracellular matrix that covers the ciliary outer segment of the sensory process
      and that shows organizational defects in nompA mutants. The structure and
      location of NompA suggest that it forms part of a mechanical linkage required to
      transmit mechanical stimuli to the transduction apparatus.

PMID- 11239433
TI  - Plexina1 autoinhibition by the plexin sema domain.
AB  - Semaphorin 3A (Sema3A) binds to neuropilin-1 (NP1) and activates the
      transmembrane Plexin to transduce a repulsive axon guidance signal. Here, we show
      that Sema3 signals are transduced equally effectively by PlexinA1 or PlexinA2,
      but not by PlexinA3. Deletion analysis of the PlexinA1 ectodomain demonstrates
      that the sema domain prevents PlexinA1 activation in the basal state. Sema
      deleted PlexinA1 is constitutively active, producing cell contraction, growth
      cone collapse, and inhibition of neurite outgrowth. The sema domain of PlexinA1
      physically associates with the remainder of the PlexinA1 ectodomain and can
      reverse constitutive activation. Both the sema portion and the remainder of the
      ectodomain of PlexinA1 associate with NP1 in a Sema3A-independent fashion. Plexin
      A1 is autoinhibited by its sema domain, and Sema3A/NP1 releases this inhibition.

PMID- 11239434
TI  - Electrical activity modulates growth cone guidance by diffusible factors.
AB  - Brief periods of electrical stimulation of cultured Xenopus spinal neurons
      resulted in a marked alteration in the turning responses of the growth cone
      induced by gradients of attractive or repulsive guidance cues. Netrin-1-induced
      attraction was enhanced, and the repulsion induced by myelin-associated
      glycoprotein (MAG) or myelin membrane fragments was converted to attraction. The
      effect required the presence of extracellular Ca(2+) during electrical
      stimulation and appeared to be mediated by an elevation of both cytoplasmic
      Ca(2+) and cAMP. Thus, electrical activity may influence the axonal path finding
      of developing neurons, and intermittent electrical stimulation may be effective
      in promoting nerve regeneration after injury.

PMID- 11239435
TI  - Role of molecular oscillations in generating behavioral rhythms in Drosophila.
AB  - Circadian oscillations of clock gene products are thought to provide time-of-day
      signals that drive overt rhythms. In Drosophila, RNA and protein levels of the
      period and timeless genes oscillate and the proteins autoregulate their
      transcription. To test the relevance of these oscillations, we expressed period
      and timeless under control of constitutively active promoters. Constitutive
      expression of either RNA supported protein cycling and behavioral rhythms in the
      respective null mutant, although constitutive timeless was less effective than
      constitutive period. Constitutive expression of both genes restored behavioral
      rhythms that showed deficits in photic resetting and drove cyclic expression of
      the clock-controlled RNA, vrille. Overexpression of either period or timeless,
      but especially timeless, attenuated behavioral rhythmicity and protein cycling in
      lateral neurons. We propose that the two proteins must cycle to drive rhythmic
      expression of downstream genes.

PMID- 11239436
TI  - A developmental switch in neurotransmitter flux enhances synaptic efficacy by
      affecting AMPA receptor activation.
AB  - Formation of glutamatergic synapses entails development of "silent" immature
      contacts into mature functional synapses. To determine how this transformation
      occurs, we investigated the development of neurotransmission at single synapses
      in vitro. Maturation of presynaptic function, assayed with endocytotic markers,
      followed accumulation of synapsin I. During this period, synaptic transmission
      was primarily mediated by activation of NMDA receptors, suggesting that most
      synapses were functionally silent. However, local glutamate application to silent
      synapses indicated that these synapses contained functional AMPA receptors,
      suggesting a possible presynaptic locus for silent transmission. Interference
      with presynaptic vesicle fusion by exposure to tetanus toxin reverted functional
      to silent transmission, implicating SNARE-mediated fusion as a determinant of the
      ratio of NMDA:AMPA receptor activation. This work reveals that functional
      maturation of synaptic transmission involves transformation of presynaptic silent
      secretion into mature synaptic transmitter release.

PMID- 11239437
TI  - CAKbeta/Pyk2 kinase is a signaling link for induction of long-term potentiation
      in CA1 hippocampus.
AB  - Long-term potentiation (LTP) is an activity-dependent enhancement of synaptic
      efficacy, considered a model of learning and memory. The biochemical cascade
      producing LTP requires activation of Src, which upregulates the function of NMDA
      receptors (NMDARs), but how Src becomes activated is unknown. Here, we show that
      the focal adhesion kinase CAKbeta/Pyk2 upregulated NMDAR function by activating
      Src in CA1 hippocampal neurons. Induction of LTP was prevented by blocking
      CAKbeta/Pyk2, and administering CAKbeta/Pyk2 intracellularly mimicked and
      occluded LTP. Tyrosine phosphorylation of CAKbeta/Pyk2 and its association with
      Src was increased by stimulation that produced LTP. Finally, CAKbeta/Pyk2
      stimulated enhancement of synaptic AMPA responses was prevented by blocking
      NMDARS, chelating intracellular Ca(2+), or blocking Src. Thus, activating
      CAKbeta/Pyk2 is required for inducing LTP and may depend upon downstream
      activation of Src to upregulate NMDA receptors.

PMID- 11239439
TI  - Eye position influences auditory responses in primate inferior colliculus.
AB  - We examined the frame of reference of auditory responses in the inferior
      colliculus in monkeys fixating visual stimuli at different locations. Eye
      position modulated the level of auditory responses in 33% of the neurons we
      encountered, but it did not appear to shift their spatial tuning. The effect of
      eye position on auditory responses was substantial-comparable in magnitude to
      that of sound location. The eye position signal appeared to interact with the
      auditory responses in at least a partly multiplicative fashion. We conclude that
      the representation of sound location in primate IC is distributed and that the
      frame of reference is intermediate between head- and eye-centered coordinates.
      The information contained in these neurons appears to be sufficient for later
      neural stages to calculate the positions of sounds with respect to the eyes.

PMID- 11239438
TI  - Presynaptic kainate receptors that enhance the release of GABA on CA1 hippocampal
      interneurons.
AB  - We report that kainate receptors are present on presynaptic GABAergic terminals
      contacting interneurons and that their activation increases GABA release.
      Application of kainate increased the frequency of miniature inhibitory
      postsynaptic currents recorded in CA1 interneurons. Local applications of
      glutamate but not of AMPA or NMDA also increased GABA quantal release.
      Application of kainate as well as synaptically released glutamate reduced the
      number of failures of GABAergic neurotransmission between interneurons. Thus,
      activation of presynaptic kainate receptors increases the probability of GABA
      release at interneuron-interneuron synapses. Glutamate may selectively control
      the communication between interneurons by increasing their mutual inhibition.

PMID- 11239440
TI  - Orientation preference patterns in mammalian visual cortex: a wire length
      minimization approach.
AB  - In the visual cortex of many mammals, orientation preference changes smoothly
      along the cortical surface, with the exception of singularities such as pinwheels
      and fractures. The reason for the existence of these singularities has remained
      elusive, suggesting that they are developmental artifacts. We show that
      singularities reduce the length of intracortical neuronal connections for some
      connection rules. Therefore, pinwheels and fractures could be evolutionary
      adaptations keeping cortical volume to a minimum. Wire length minimization
      approach suggests that interspecies differences in orientation preference maps
      reflect differences in intracortical neuronal circuits, thus leading to
      experimentally testable predictions. We discuss application of our model to
      direction preference maps.

PMID- 11239441
TI  - Cortical mechanisms specific to explicit visual object recognition.
AB  - The cortical mechanisms associated with conscious object recognition were studied
      using functional magnetic resonance imaging (fMRI). Participants were required to
      recognize pictures of masked objects that were presented very briefly, randomly
      and repeatedly. This design yielded a gradual accomplishment of successful
      recognition. Cortical activity in a ventrotemporal visual region was linearly
      correlated with perception of object identity. Therefore, although object
      recognition is rapid, awareness of an object's identity is not a discrete
      phenomenon but rather associated with gradually increasing cortical activity.
      Furthermore, the focus of the activity in the temporal cortex shifted anteriorly
      as subjects reported an increased knowledge regarding identity. The results
      presented here provide new insights into the processes underlying explicit object
      recognition, as well as the analysis that takes place immediately before and
      after recognition is possible.

PMID- 11239442
TI  - Neural activity in the human brain relating to uncertainty and arousal during
      anticipation.
AB  - We used functional magnetic resonance neuroimaging to measure brain activity
      during delay between reward-related decisions and their outcomes, and the
      modulation of this delay activity by uncertainty and arousal. Feedback,
      indicating financial gain or loss, was given following a fixed delay.
      Anticipatory arousal was indexed by galvanic skin conductance. Delay-period
      activity was associated with bilateral activation in orbital and medial
      prefrontal, temporal, and right parietal cortices. During delay, activity in
      anterior cingulate and orbitofrontal cortices was modulated by outcome
      uncertainty, whereas anterior cingulate, dorsolateral prefrontal, and parietal
      cortices activity was modulated by degree of anticipatory arousal. A distinct
      region of anterior cingulate was commonly activated by both uncertainty and
      arousal. Our findings highlight distinct contributions of cognitive uncertainty
      and autonomic arousal to anticipatory neural activity in prefrontal cortex.

PMID- 11239443
TI  - Contrasting roles of IL-2 and IL-15 in the life and death of lymphocytes:
      implications for immunotherapy.

PMID- 11239444
TI  - Targeting of lymphotoxin-alpha to the tumor elicits an efficient immune response
      associated with induction of peripheral lymphoid-like tissue.
AB  - A recombinant antibody-lymphotoxin-alpha fusion protein induced an adaptive
      immune response protecting mice from melanoma. Importantly, this fusion protein
      elicited the formation of a lymphoid-like tissue in the tumor microenvironment
      containing L-selectin+ T cells and MHC class II+ antigen-presenting cells, as
      well as B and T cell aggregates. Furthermore, PNAd+/TCA4+ high endothelial
      venules were observed within the tumor, suggesting entry channels for naive T
      cell infiltrates. Over the course of therapy, a marked clonal expansion of
      certain TCR specificities occurred among tumor-infiltrating lymphocytes that
      displayed reactivity against melanoma cells and the TRP-2(180-188) peptide.
      Consequently, naive T cells may have been recruited to as well as primed and
      expanded in the lymphoid-like tissue induced by the lymphotoxin-alpha fusion
      protein at the tumor site.

PMID- 11239445
TI  - ULBPs, novel MHC class I-related molecules, bind to CMV glycoprotein UL16 and
      stimulate NK cytotoxicity through the NKG2D receptor.
AB  - The human cytomegalovirus glycoprotein, UL16, binds to two members of a novel
      family of molecules, the ULBPs, and to the MHC class I homolog, MICB. The ULBPs
      are GPI-linked glycoproteins belonging to the extended MHC class I family but are
      only distantly related to MICB. The ULBP and MICB molecules are ligands for the
      activating receptor, NKG2D/DAP10, and this interaction is blocked by a soluble
      form of UL16. The ULBPs stimulate cytokine and chemokine production from NK
      cells, and expression of ULBPs in NK cell-resistant target cells confers
      susceptibility to NK cell cytotoxicity. Masking of NK cell recognition of ULBP or
      MIC antigens by UL16 provides a potential mechanism by which human
      cytomegalovirus-infected cells might evade attack by the immune system.

PMID- 11239446
TI  - Increased TCR avidity after T cell activation: a mechanism for sensing low
      density antigen.
AB  - While activated T cells are known to have enhanced biological responses to
      antigen stimulation, the biophysical basis of this increased sensitivity remains
      unknown. Here, we show that, on activated T cells, the TCR avidity for peptide
      MHC complexes is 20- to 50-fold higher than the TCR avidity of naive T cells.
      This increased avidity for peptide-MHC depends on TCR reorganization and is
      sensitive to the cholesterol content of the T cell membrane. Analysis of the
      binding data indicates the enhanced avidity is due to increases in cross-linking
      of TCR on activated T cells. Activation-induced membrane (AIM) changes in TCR
      avidity represent a previously unrecognized means of increasing the sensitivity
      of activated T cells to small amounts of antigen in the periphery.

PMID- 11239447
TI  - CTLA-4 regulates induction of anergy in vivo.
AB  - The requirement for CTLA-4 during the induction of peripheral T cell tolerance in
      vivo was investigated using naive TCR transgenic T cells lacking CTLA-4. CTLA-4(
      /-) T cells are resistant to tolerance induction, as demonstrated by their
      proliferative responses, IL-2 production, and progression into the cell cycle.
      Following exposure to a tolerogenic stimulus in vivo and restimulation in vitro,
      wild-type T cells are blocked at the late G1 to S restriction point of the cell
      cycle. In contrast, CTLA-4(-/-) T cells enter into the S phase of the cell cycle,
      as shown by downregulation of p27(kip1), elevated cdk2 kinase activity, and Rb
      hyperphosphorylation. Thus, CTLA-4 has an essential role in determining the
      outcome of T cell encounter with a tolerogenic stimulus.

PMID- 11239448
TI  - Identification and characterization of a novel OCA-B isoform. implications for a
      role in B cell signaling pathways.
AB  - OCA-B is a B lymphocyte-specific transcription coactivator that mediates tissue-
      and stage-restricted transcription of immunoglobulin genes. Earlier genetic
      studies revealed that OCA-B is essential for germinal center formation and
      production of secondary immunoglobulin isotypes. Biochemically purified OCA-B
      contains p35 and p34 isoforms, and a further analysis has now revealed that p35
      is derived from a newly found isoform, p40. More importantly, it has been found
      that p35 is myristoylated in vivo and that this leads to dramatic changes
      (including localization to membrane compartments) in its properties. These
      results suggest that the p35 isoform of OCA-B has functions distinct from those
      of the nuclear p34 and that it might be a component of a signaling pathway that
      is required for late-stage B cell development.

PMID- 11239449
TI  - The CD19/CD21 complex functions to prolong B cell antigen receptor signaling from
      lipid rafts.
AB  - The CD19/CD21 complex functions to significantly enhance B cell antigen receptor
      (BCR) signaling in response to complement-tagged antigens. Recent studies showed
      that following antigen binding the BCR translocates into plasma membrane lipid
      rafts that serve as platforms for BCR signaling. Here, we show that the binding
      of complement-tagged antigens stimulates the translocation of both the BCR and
      the CD19/CD21 complex into lipid rafts, resulting in prolonged residency in and
      signaling from the rafts, as compared to BCR cross-linking alone. When coligated
      to the BCR, the CD19/CD21 complex retards the internalization and degradation of
      the BCR. The colocalization and stabilization of the BCR and the CD19/CD21
      complex in plasma membrane lipid rafts represents a novel mechanism by which a
      coreceptor enhances BCR signaling.

PMID- 11239451
TI  - STAT-3 activation is required for normal G-CSF-dependent proliferation and
      granulocytic differentiation.
AB  - To investigate the role of signal transducer and activator of transcription
      (STAT) proteins in granulocyte colony-stimulating factor (G-CSF)-regulated
      biological responses, we generated transgenic mice with a targeted mutation of
      their G-CSF receptor (termed d715F) that abolishes G-CSF-dependent STAT-3
      activation and attenuates STAT-5 activation. Homozygous mutant mice are severely
      neutropenic with an accumulation of immature myeloid precursors in their bone
      marrow. G-CSF-induced proliferation and granulocytic differentiation of
      hematopoietic progenitors is severely impaired. Expression of a constitutively
      active form of STAT-3 in d715F progenitors nearly completely rescued these
      defects. Conversely, expression of a dominant-negative form of STAT-3 in wild
      type progenitors results in impaired G-CSF-induced proliferation and
      differentiation. These data suggest that STAT-3 activation by the G-CSFR is
      critical for the transduction of normal proliferative signals and contributes to
      differentiative signals.

PMID- 11239452
TI  - Selective export of MHC class I molecules from the ER after their dissociation
      from TAP.

PMID- 11239450
TI  - Fas is required for clonal selection in germinal centers and the subsequent
      establishment of the memory B cell repertoire.
AB  - In T cell-dependent immune responses, high-affinity B cells are selected and
      differentiate into memory cells; however, the mechanism behind this process
      remains largely unknown. Here, we report that the selection of high-affinity B
      cells within germinal centers (GCs) is impaired in Fas-deficient lpr mice in the
      primary response, probably owing to inefficient negative selection. The memory
      compartment in control mice is mostly established by precursors generated from
      the early GCs, whereas the lpr defect expands the memory compartment by the
      increased recruitment of newly generated precursors from the late GCs, resulting
      in the accumulation of heavily mutated memory B cells at high frequency. These
      results suggest that Fas is required for clonal selection within GCs and the
      establishment of the memory B cell repertoire.

PMID- 11239453
TI  - Positional cloning of a novel Fanconi anemia gene, FANCD2.
AB  - Fanconi anemia (FA) is a genetic disease with birth defects, bone marrow failure,
      and cancer susceptibility. To date, genes for five of the seven known
      complementation groups have been cloned. Complementation group D is
      heterogeneous, consisting of two distinct genes, FANCD1 and FANCD2. Here we
      report the positional cloning of FANCD2. The gene consists of 44 exons, encodes a
      novel 1451 amino acid nuclear protein, and has two protein isoforms. Similar to
      other FA proteins, the FANCD2 protein has no known functional domains, but unlike
      other known FA genes, FANCD2 is highly conserved in A. thaliana, C. elegans, and
      Drosophila. Retroviral transduction of the cloned FANCD2 cDNA into FA-D2 cells
      resulted in functional complementation of MMC sensitivity.

PMID- 11239454
TI  - Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway.
AB  - Fanconi anemia (FA) is a human autosomal recessive cancer susceptibility disorder
      characterized by cellular sensitivity to mitomycin C and ionizing radiation.
      Although six FA genes (for subtypes A, C, D2, E, F, and G) have been cloned,
      their relationship to DNA repair remains unknown. In the current study, we show
      that a nuclear complex containing the FANCA, FANCC, FANCF, and FANCG proteins is
      required for the activation of the FANCD2 protein to a monoubiquitinated isoform.
      In normal (non-FA) cells, FANCD2 is monoubiquitinated in response to DNA damage
      and is targeted to nuclear foci (dots). Activated FANCD2 protein colocalizes with
      the breast cancer susceptibility protein, BRCA1, in ionizing radiation-induced
      foci and in synaptonemal complexes of meiotic chromosomes. The FANCD2 protein,
      therefore, provides the missing link between the FA protein complex and the
      cellular BRCA1 repair machinery. Disruption of this pathway results in the
      cellular and clinical phenotype common to all FA subtypes.

PMID- 11239455
TI  - BRCA2 is required for homology-directed repair of chromosomal breaks.
AB  - The BRCA2 tumor suppressor has been implicated in the maintenance of chromosomal
      stability through a function in DNA repair. In this report, we examine human and
      mouse cell lines containing different BRCA2 mutations for their ability to repair
      chromosomal breaks by homologous recombination. Using the I-SceI endonuclease to
      introduce a double-strand break at a specific chromosomal locus, we find that
      BRCA2 mutant cell lines are recombination deficient, such that homology-directed
      repair is reduced 6- to >100-fold, depending on the cell line. Thus, BRCA2 is
      essential for efficient homology-directed repair, presumably in conjunction with
      the Rad51 recombinase. We propose that impaired homology-directed repair caused
      by BRCA2 deficiency leads to chromosomal instability and, possibly,
      tumorigenesis, through lack of repair or misrepair of DNA damage.

PMID- 11239456
TI  - Role of BRCA2 in control of the RAD51 recombination and DNA repair protein.
AB  - Individuals carrying BRCA2 mutations are predisposed to breast and ovarian
      cancers. Here, we show that BRCA2 plays a dual role in regulating the actions of
      RAD51, a protein essential for homologous recombination and DNA repair. First,
      interactions between RAD51 and the BRC3 or BRC4 regions of BRCA2 block
      nucleoprotein filament formation by RAD51. Alterations to the BRC3 region that
      mimic cancer-associated BRCA2 mutations fail to exhibit this effect. Second,
      transport of RAD51 to the nucleus is defective in cells carrying a cancer
      associated BRCA2 truncation. Thus, BRCA2 regulates both the intracellular
      localization and DNA binding ability of RAD51. Loss of these controls following
      BRCA2 inactivation may be a key event leading to genomic instability and
      tumorigenesis.

PMID- 11239457
TI  - A DNA damage-induced p53 serine 392 kinase complex contains CK2, hSpt16, and
      SSRP1.
AB  - Phosphorylation of the human p53 protein at Ser-392 has been shown to be
      responsive to UV but not gamma irradiation. Here we describe identification and
      purification of a mammalian UV-activated protein kinase complex that
      phosphorylates Ser-392 of p53 in vitro. This kinase complex contains casein
      kinase 2 (CK2) and the chromatin transcriptional elongation factor FACT (a
      heterodimer of hSpt16 and SSRP1). In vitro studies show that FACT alters the
      specificity of CK2 in the complex such that it selectively phosphorylates p53
      over other substrates including casein. In addition, phosphorylation by the
      kinase complex enhances p53 activity. These results thus provide a potential
      mechanism for p53 activation by UV irradiation.

PMID- 11239458
TI  - Regulation of Saccharomyces Rad53 checkpoint kinase during adaptation from DNA
      damage-induced G2/M arrest.
AB  - Saccharomyces cells with one unrepaired double-strand break (DSB) adapt after
      checkpoint-mediated G2/M arrest. Adaptation is accompanied by loss of Rad53p
      checkpoint kinase activity and Chk1p phosphorylation. Rad53p kinase remains
      elevated in yku70delta and cdc5-ad cells that fail to adapt. Permanent G2/M
      arrest in cells with increased single-stranded DNA is suppressed by the rfa1-t11
      mutation, but this RPA mutation does not suppress permanent arrest in cdc5-ad
      cells. Checkpoint kinase activation and inactivation can be followed in G2
      arrested cells, but there is no kinase activation in G1-arrested cells. We
      conclude that activation of the checkpoint kinases in response to a single DNA
      break is cell cycle regulated and that adaptation is an active process by which
      these kinases are inactivated.

PMID- 11239459
TI  - The mechanism of type IA topoisomerase-mediated DNA topological transformations.
AB  - Type IA DNA topoisomerases possess several domains forming a toroidal molecule
      with a central hole large enough to accommodate single- or double-stranded DNA.
      The sign inversion model predicts several protein-DNA intermediates, including
      those in which DNA is trapped within the hole. Opposing cysteine residues were
      incorporated into two independent domains surrounding the putative DNA binding
      cavity of E. coli topoisomerase III, creating a molecule that can be covalently
      closed or opened by oxidizing or reducing the disulfide bond. The formation of
      the disulfide bond allowed the trapping of single- and double-stranded DNA within
      the cavity of the enzyme and the identification of other intermediates proposed
      by the sign inversion model.

PMID- 11239460
TI  - Nhp6, an HMG1 protein, functions in SNR6 transcription by RNA polymerase III in
      S. cerevisiae.
AB  - Nhp6A and Nhp6B are HMG1-like proteins required for the growth of S. cerevisiae
      at elevated temperatures. We show that the conditional lethality of an nhp6
      strain results from defective transcription of SNR6 (U6 snRNA) by RNA polymerase
      III. Overexpression of U6 snRNA or Brf1, a limiting component of TFIIIB, and an
      activating mutation (PCF1-1) in TFIIIC were each found to suppress the nhp6
      growth defect. Additionally, U6 snRNA levels, which are reduced over 10-fold in
      nhp6 cells at 37 degrees C, were restored by Brf1 overexpression and by PCF1-1.
      Nhp6A protein specifically enhanced TFIIIC-dependent, but not TATA box-dependent,
      SNR6 transcription in vitro by facilitating TFIIIC binding to the SNR6 promoter.
      Thus, Nhp6 has a direct role in transcription complex assembly at SNR6.

PMID- 11239461
TI  - A biochemical function for the Sm complex.
AB  - Within the yeast commitment complex, SmB, SmD1, and SmD3 make direct contact with
      the pre-mRNA substrate, close to the 5' splice site. Only these three Sm proteins
      have long and highly charged C-terminal tails, in metazoa as well as in yeast. We
      replaced these proteins with tail-truncated versions. Genetic assays demonstrate
      that the tails contribute to similar and overlapping functions, and cross-linking
      assays show that the tails make direct contact with the pre-mRNA in a largely
      sequence-independent manner. Other biochemical assays indicate that they function
      at least in part to stabilize the U1 snRNP-pre-mRNA interaction. We speculate
      that this role may be general, and may have even evolved to aid weak
      intermolecular nucleic acid interactions of only a few base pairs.

PMID- 11239462
TI  - SC35 plays a role in T cell development and alternative splicing of CD45.
AB  - Molecular diversity via alternative splicing is important for cellular function
      and development. SR proteins are strong candidate regulators of alternative
      splicing because they can modulate splice site selection. However, endogenous
      substrates for SR proteins are largely unknown, and their roles as splicing
      regulators in vertebrate development are unclear. Here we report that Cre
      mediated conditional deletion of the prototypical SR protein SC35 in the thymus
      causes a defect in T cell maturation. Deletion of SC35 alters alternative
      splicing of CD45, a receptor tyrosine phosphatase known to be regulated by
      differential splicing during thymocyte development and activation. This study
      establishes a model to address the function of SR proteins in physiological
      settings and reveals a critical role of SC35 in a T cell-specific regulated
      splicing pathway.

PMID- 11239463
TI  - The two PDGF receptors maintain conserved signaling in vivo despite divergent
      embryological functions.
AB  - Gene targeting studies have indicated that the two receptors for PDGF, alpha and
      beta, direct unique functions during development. Distinct ligand affinities,
      patterns of gene expression, and/or mechanisms of signal relay may account for
      functional specificity of the two PDGF receptor isoforms. To distinguish between
      these factors, we have created two complementary lines of knockin mice in which
      the intracellular signaling domains of one PDGFR have been removed and replaced
      by those of the other PDGFR. While both lines demonstrated substantial rescue of
      normal development, substitution of the PDGFbetaR signaling domains with those of
      the PDGFalphaR resulted in varying degrees of vascular disease. This observation
      provides a framework for discussing the evolution of receptor tyrosine kinase
      functional specificity.

PMID- 11239464
TI  - RING finger mutations that abolish c-Cbl-directed polyubiquitination and
      downregulation of the EGF receptor are insufficient for cell transformation.
AB  - The c-Cbl protooncogene can function as a negative regulator of receptor protein
      tyrosine kinases (RPTKs) by targeting activated receptors for polyubiquitination
      and downregulation. This function requires its tyrosine kinase binding (TKB)
      domain for targeting RPTKs and RING finger domain to recruit E2 ubiquitin
      conjugating enzymes. It has therefore been proposed that oncogenic Cbl proteins
      act in a dominant-negative manner to block this c-Cbl activity. In testing this
      hypothesis, we found that although mutations spanning the RING finger abolish c
      Cbl-directed polyubiquitination and downregulation of RPTKs, they do not induce
      transformation. In contrast, it is mutations within a highly conserved alpha
      helical structure linking the SH2 and RING finger domains that render Cbl
      proteins oncogenic. Thus, Cbl transformation involves effects additional to
      polyubiquitination of RPTKs that are independent of the RING finger and its
      ability to recruit E2-conjugating enzymes.

PMID- 11239465
TI  - Asymmetric localization of frizzled and the establishment of cell polarity in the
      Drosophila wing.
AB  - The frizzled gene of Drosophila encodes a transmembrane receptor molecule
      required for cell polarity decisions in the adult cuticle. In the wing, a single
      trichome is produced by each cell, which normally points distally. In the absence
      of frizzled function, the trichomes no longer point uniformly distalward. We
      report that during cell polarization, the Frizzled receptor is localized to the
      distal cell edge, probably resulting in asymmetric Frizzled activity across the
      axis of the cell. Furthermore, Frizzled localization correlates with subsequent
      trichome polarity, suggesting that it may be an instructive cue in the
      determination of cell polarity. This differential receptor distribution may
      represent a novel mechanism for amplifying small differences in signaling
      activity across the axis of a cell.

PMID- 11239466
TI  - The erythropoietin receptor cytosolic juxtamembrane domain contains an essential,
      precisely oriented, hydrophobic motif.
AB  - We report that the erythropoietin receptor cytosolic juxtamembrane region is
      conformationally rigid and contains a hydrophobic motif, composed of residues
      L253, I257, and W258, that is crucial for Janus kinase 2 (JAK2) activation and
      receptor signaling. Alanine insertion mutagenesis shows that the orientation of
      this motif and not its distance from the membrane bilayer is critical. Intragenic
      complementation studies suggest that L253 is contained within an alpha helix
      functionally continuous to the transmembrane alpha helix. The alpha-helical
      orientation of L53 is required not for JAK2 activation but for activated JAK2 to
      induce phosphorylation of the erythropoietin receptor. This motif is highly
      conserved among cytokine receptors and couples ligand-induced conformational
      changes in the receptor to intracellular activation of JAK2.

PMID- 11239467
TI  - Solution structure of ERK2 binding domain of MAPK phosphatase MKP-3: structural
      insights into MKP-3 activation by ERK2.
AB  - MAP kinases (MAPKs), which control mitogenic signal transduction in all
      eukaryotic organisms, are inactivated by dual specificity MAPK phosphatases
      (MKPs). MKP-3, a prototypical MKP, achieves substrate specificity through its N
      terminal domain binding to the MAPK ERK2, resulting in the activation of its C
      terminal phosphatase domain. The solution structure and biochemical analysis of
      the ERK2 binding (EB) domain of MKP-3 show that regions that are essential for
      ERK2 binding partly overlap with its sites that interact with the C-terminal
      catalytic domain, and that these interactions are functionally coupled to the
      active site residues of MKP-3. Our findings suggest a novel mechanism by which
      the EB domain binding to ERK2 is transduced to cause a conformational change of
      the C-terminal catalytic domain, resulting in the enzymatic activation of MKP-3.

PMID- 11239468
TI  - NF-kappaB-inducing kinase regulates the processing of NF-kappaB2 p100.
AB  - Processing of the nf(kappa)b2 gene product p100 to generate p52 is an important
      step in NF-kappaB regulation. We show that this step is negatively regulated by a
      processing-inhibitory domain (PID) within p100 and positively regulated by the NF
      kappaB-inducing kinase (NIK). While the PID suppresses the constitutive
      processing of p100, NIK induces p100 processing by stimulating site-specific
      phosphorylation and ubiquitination of this precursor protein. Further, a natural
      mutation of the gene encoding NIK in alymphoplasia (aly) mice cripples the
      function of NIK in p100 processing, causing a severe defect in p52 production.
      These data suggest that NIK is a specific kinase regulating p100 processing and
      explain why the aly and nf(kappa)b2 knockout mice exhibit similar immune
      deficiencies.

PMID- 11239469
TI  - Lack of proteasome active site allostery as revealed by subunit-specific
      inhibitors.
AB  - The chymotrypsin-like (CT-L) activity of the proteasome is downregulated by
      substrates of the peptidyl-glutamyl peptide hydrolyzing (PGPH) activity. To
      investigate the nature of such interactions, we synthesized selective
      alpha',beta'-epoxyketone inhibitors of the PGPH activity. In cellular
      proliferation and protein degradation assays, these inhibitors revealed that
      selective PGPH inhibition was insufficient to inhibit protein degradation,
      indicating that the CT-L and PGPH sites function independently. We also
      demonstrated that CT-L inhibition by a PGPH substrate does not require the
      occupancy of the PGPH site or hydrolysis of the PGPH substrate. Thus, these
      results support a model in which a substrate of one subunit regulates the
      activity of another via binding to a noncatalytic site(s) rather than through
      binding to an active site.

PMID- 11239470
TI  - The stress-induced MAP kinase p38 regulates endocytic trafficking via the
      GDI:Rab5 complex.
AB  - Early endocytic membrane traffic is regulated by the small GTPase Rab5, which
      cycles between GTP- and GDP-bound states as well as between membrane and cytosol.
      The latter cycle depends on GDI, which functions as a Rab vehicle in the aqueous
      environment of the cytosol. Here, we report that formation of the GDI:Rab5
      complex is stimulated by a cytosolic factor that we purified and then identified
      as p38 MAPK. We find that p38 regulates GDI in the cytosolic cycle of Rab5 and
      modulates endocytosis in vivo. Our observations reveal the existence of a cross
      talk between endocytosis and the p38-dependent stress response, thus providing
      molecular evidence that endocytosis can be regulated by the environment.

PMID- 11239471
TI  - TRAPP I implicated in the specificity of tethering in ER-to-Golgi transport.
AB  - TRAPP is a conserved protein complex required early in the secretory pathway.
      Here, we report two forms of TRAPP, TRAPP I and TRAPP II, that mediate different
      transport events. Using chemically pure TRAPP I and COPII vesicles, we have
      reconstituted vesicle targeting in vitro. The binding of COPII vesicles to TRAPP
      I is specific, blocked by GTPgammaS, and, surprisingly, does not require other
      tethering factors. Our findings imply that TRAPP I is the receptor on the Golgi
      for COPII vesicles. Once the vesicle binds to TRAPP I, the small GTP binding
      protein Ypt1p is activated and other tethering factors are recruited.

PMID- 11239472
TI  - The class II phosphoinositide 3-kinase C2alpha is activated by clathrin and
      regulates clathrin-mediated membrane trafficking.
AB  - Phosphoinositides play key regulatory roles in vesicular transport pathways in
      eukaryotic cells. Clathrin-mediated membrane trafficking has been shown to
      require phosphoinositides, but little is known about the enzyme(s) responsible
      for their formation. Here we report that clathrin functions as an adaptor for the
      class II PI 3-kinase C2alpha (PI3K-C2alpha), binding to its N-terminal region and
      stimulating its catalytic activity, especially toward phosphorylated inositide
      substrates. Further, we show that endogenous PI3K-C2alpha is localized in coated
      pits and that exogenous expression affects clathrin-mediated endocytosis and
      sorting in the trans-Golgi network. These findings provide a mechanistic basis
      for localized inositide generation at sites of clathrin-coated bud formation,
      which, with recruitment of inositide binding proteins and subsequent synaptojanin
      mediated phosphoinositide hydrolysis, may regulate coated vesicle formation and
      uncoating.

PMID- 11239480
TI  - How understanding the control of energy metabolism can help investigation of
      mitochondrial dysfunction, regulation and pharmacology.
AB  - Understanding the control of mitochondrial energy metabolism is central to
      knowing how mitochondria function within cells. Metabolic control analysis is the
      best approach available for studying the control of mitochondrial energy
      metabolism. Here I outline how metabolic control analysis has been used to help
      understand mitochondrial regulation, damage and pharmacology.

PMID- 11239481
TI  - Control of oxidative phosphorylation in skeletal muscle.
AB  - The classical concept of ATP-demand control of energy metabolism in skeletal
      muscle has to be modified on the basis of studies showing the influence of
      additional controlling parameters (reducing equivalent supply, oxygen
      availability, proton leak, diffusion restrictions and the creatine kinase system)
      and on the basis of applications of metabolic control analysis showing very
      clearly multistep control. This concept of multistep control allows to quantify
      the individual influence of any parameter on mitochondrial oxidative
      phosphorylation and is extremely helpful to analyze the metabolic consequences of
      enzyme deficiencies in skeletal muscle occurring in mitochondrial myopathies.

PMID- 11239482
TI  - What do mitochondrial diseases teach us about normal mitochondrial
      functions...that we already knew: threshold expression of mitochondrial defects.
AB  - This paper shows how metabolic control analysis (MCA) can help to explain two
      important features of mitochondrial diseases: (i) the existence of a threshold in
      the expression of the complex deficiencies on the respiratory flux or on ATP
      synthesis, i.e. the fact that it is necessary to have a large complex deficiency
      in order to observe a substantial decrease in these fluxes; (ii) the tissue
      specificity, i.e. the fact that all tissues are not affected, even if the complex
      deficiency is present in all of them. We also show the limits of MCA,
      particularly when considering the in vivo situation. However, MCA offers a new
      way to consider mitochondrial diseases. The fact that fluxes only slightly
      change, when a complex is affected, is done at the expense of great changes in
      intermediate metabolite concentrations; intermediate metabolites situated
      upstream from the deficient complex are more reduced, leading to a greater
      generation of free radicals. This could bring an explanation for the diseases
      observed in conditions where the mitochondrial rate of ATP synthesis is only
      slightly affected.

PMID- 11239483
TI  - Theoretical studies on the regulation of oxidative phosphorylation in intact
      tissues.
AB  - The theoretical studies on the regulation of oxidative phosphorylation that were
      performed with the aid of kinetic models of this process are overviewed. A
      definition of the regulation of the flux through a metabolic pathway is proposed
      and opposed to the control exerted by particular enzymes over this flux.
      Different kinetic models of oxidative phosphorylation proposed in the literature
      are presented, of which only the model proposed by myself and co-workers was
      extensively used in theoretical studies on the regulation and compensation in the
      oxidative phosphorylation system. These theoretical studies have led to the
      following conclusions: (1) in isolated mitochondria, an increase in the activity
      of an artificial ATP-using system stimulates mitochondria mainly via changes in
      [ADP], while changes in [ATP] and [P(i)] play only a minor role; (2) in non
      excitable tissues (e.g. liver), hormones (acting via some cytosolic factor(s))
      activate directly both ATP usage and at least some enzymes of the ATP-producing
      block; (3) in excitable tissues (e.g. skeletal muscle), neural signals stimulate
      (via some cytosolic factor(s)) in parallel all the steps of oxidative
      phosphorylation together with ATP usage and substrate dehydrogenation; (4) the
      decrease in the flux through cytochrome oxidase caused by a decrease in oxygen
      concentration is, at least partially, compensated by a decrease in Delta p and
      increase in the reduction level of cytochrome c. A theoretical prediction is
      formulated that there should exist and be observable a universal cytosolic
      factor/regulatory mechanism which directly activates (at least in excitable
      tissues) all complexes of oxidative phosphorylation during an increased energy
      demand.

PMID- 11239484
TI  - Regulation of mitochondrial respiration by nitric oxide inhibition of cytochrome
      c oxidase.
AB  - Nitric oxide (NO) and its derivatives inhibit mitochondrial respiration by a
      variety of means. Nanomolar concentrations of NO immediately, specifically and
      reversibly inhibit cytochrome oxidase in competition with oxygen, in isolated
      cytochrome oxidase, mitochondria, nerve terminals, cultured cells and tissues.
      Higher concentrations of NO and its derivatives (peroxynitrite, nitrogen dioxide
      or nitrosothiols) can cause irreversible inhibition of the respiratory chain,
      uncoupling, permeability transition, and/or cell death. Isolated mitochondria,
      cultured cells, isolated tissues and animals in vivo display respiratory
      inhibition by endogenously produced NO from constitutive isoforms of NO synthase
      (NOS), which may be largely mediated by NO inhibition of cytochrome oxidase.
      Cultured cells expressing the inducible isoform of NOS (iNOS) can acutely and
      reversibly inhibit their own cellular respiration and that of co-incubated cells
      due to NO inhibition of cytochrome oxidase, but after longer-term incubation
      result in irreversible inhibition of cellular respiration due to NO or its
      derivatives. Thus the NO inhibition of cytochrome oxidase may be involved in the
      physiological and/or pathological regulation of respiration rate, and its
      affinity for oxygen.

PMID- 11239485
TI  - Control of plant mitochondrial respiration.
AB  - Plant mitochondria are characterised by the presence of both phosphorylating
      (cytochrome) and non-phosphorylating (alternative) respiratory pathways, the
      relative activities of which directly affect the efficiency of mitochondrial
      energy conservation. Different approaches to study the regulation of the
      partitioning of reducing equivalents between these routes are critically
      reviewed. Furthermore, an updated view is provided regarding the understanding of
      plant mitochondrial respiration in terms of metabolic control. We emphasise the
      extent to which kinetic modelling and 'top-down' metabolic control analysis
      improve the insight in phenomena related to plant mitochondrial respiration. This
      is illustrated with an example regarding the affinity of the plant alternative
      oxidase for oxygen.

PMID- 11239486
TI  - Physiological regulation of the transport activity in the uncoupling proteins
      UCP1 and UCP2.
AB  - Brown fat is a thermogenic organ that allows newborns and small mammals to
      maintain a stable body temperature when exposed to cold. The heat generation
      capacity is based on the uncoupling of respiration from ATP synthesis mediated by
      the uncoupling protein UCP1. The first studies on the properties of these
      mitochondria revealed that fatty acid removal was an absolute prerequisite for
      respiratory control. Thus fatty acids, that are substrate for oxidation, were
      proposed as regulators of respiration. However, their ability to uncouple all
      types of mitochondria and the demonstration that several mitochondrial carriers
      catalyze the translocation of the fatty acid anion have made them unlikely
      candidates for a specific role in brown fat. Nevertheless, data strongly argue
      for a physiological function. First, fatty acids mimic the noradrenaline effects
      on adipocytes. Second, there exists a precise correlation between fatty acid
      sensitivity and the levels of UCP1. Finally, fatty acids increase the conductance
      by facilitating proton translocation, a mechanism that is distinct from the fatty
      acid uncoupling mediated by other mitochondrial carriers. The regulation of UCP1
      and UCP2 by retinoids and the lack of effects of fatty acids on UCP2 or UCP3 are
      starting to set differences among the new uncoupling proteins.

PMID- 11239487
TI  - UCP1: the only protein able to mediate adaptive non-shivering thermogenesis and
      metabolic inefficiency.
AB  - The uniqueness of UCP1 (as compared to UCP2/UCP3) is evident from expression
      analysis and ablation studies. UCP1 expression is positively correlated with
      metabolic inefficiency, being increased by cold acclimation (in adults or
      perinatally) and overfeeding, and reduced in fasting and genetic obesity. Such a
      simple relationship is not observable for UCP2/UCP3. Studies with UCP1-ablated
      animals substantiate the unique role of UCP1: the phenomenon of adaptive
      adrenergic non-shivering thermogenesis in the intact animal is fully dependent on
      the presence of UCP1, and so is any kind of cold acclimation-recruited non
      shivering thermogenesis; thus UCP2/UCP3 (or any other proteins or metabolic
      processes) cannot substitute for UCP1 physiologically, irrespective of their
      demonstrated ability to show uncoupling in reconstituted systems or when
      ectopically expressed. Norepinephrine-induced thermogenesis in brown-fat cells is
      absolutely dependent on UCP1, as is the uncoupled state and the recoupling by
      purine nucleotides in isolated brown-fat mitochondria. Although very high
      UCP2/UCP3 mRNA levels are observed in brown adipose tissue of UCP1-ablated mice,
      there is no indication that the isolated brown-fat mitochondria are uncoupled;
      thus, high expression of UCP2/UCP3 does not necessarily confer to the
      mitochondria of a tissue a propensity for being innately uncoupled. Whereas the
      thermogenic effect of fatty acids in brown-fat cells is fully UCP1-dependent,
      this is not the case in brown-fat mitochondria; this adds complexity to the
      issues concerning the mechanisms of UCP1 function and the pathway from beta(3)
      adrenoceptor stimulation to UCP1 activation and thermogenesis. In addition to
      amino acid sequences conserved in all UCPs as part of the tripartite structure,
      all UCPs contain certain residues associated with nucleotide binding. However,
      conserved amongst all UCP1s so far sequenced, and without parallel in all
      UCP2/UCP3, are two sequences: 144SHLHGIKP and the C-terminal sequence
      RQTVDC(A/T)T; these sequences may therefore be essential for the unique
      thermogenic function of UCP1. The level of UCP1 in the organism is basically
      regulated at the transcriptional level (physiologically probably mainly through
      the beta(3)-adrenoceptor/CREB pathway), with influences from UCP1 mRNA stability
      and from the delay caused by translation. It is concluded that UCP1 is unique
      amongst the uncoupling proteins and is the only protein able to mediate adaptive
      non-shivering thermogenesis and the ensuing metabolic inefficiency.

PMID- 11239488
TI  - Homologues of the uncoupling protein from brown adipose tissue (UCP1): UCP2,
      UCP3, BMCP1 and UCP4.

PMID- 11239489
TI  - Mitochondrial proton leak: a role for uncoupling proteins 2 and 3?
AB  - In mitochondria ATP synthesis is not perfectly coupled to oxygen consumption due
      to proton leak across the mitochondrial inner membrane. Quantitative studies have
      shown that proton leak contributes to approximately 25% of the resting oxygen
      consumption of mammals. Proton leak plays a role in accounting for differences in
      basal metabolic rate. Thyroid studies, body mass studies, phylogenic studies and
      obesity studies have all shown that increased mass-specific metabolic rate is
      linked to increased mitochondrial proton leak. The mechanism of the proton leak
      is unclear. Evidence suggests that proton leak occurs by a non-specific diffusion
      process across the mitochondrial inner membrane. However, the high degree of
      sequence homology of the recently cloned uncoupling proteins UCP 2 and UCP 3 to
      brown adipose tissue UCP 1, and their extensive tissue distribution, suggest that
      these novel uncoupling proteins play a role in proton leak. Early indications
      from reconstitution experiments and several in vitro expression studies suggest
      that the novel uncoupling proteins uncouple mitochondria. Furthermore, mice
      overexpressing UCP 3 certainly show a phenotype consistent with increased
      metabolism. The evidence for a role for these novel UCPs in mitochondrial proton
      leak is reviewed.

PMID- 11239490
TI  - Uncoupling proteins: the issues from a biochemist point of view.
AB  - The functional characteristics of uncoupling proteins (UCP) are reviewed, with
      the main focus on the results with isolated and reconstituted proteins. UCP1 from
      brown adipose tissue, the paradigm of the UCP subfamily, is treated in more
      detail. The issues addressed are the role and mechanism of fatty acids, the
      nucleotide binding, the regulation by pH and the identification by mutagenesis of
      residues involved in these functions. The transport and regulatory functions of
      UCP2 and 3 are reviewed in comparison to UCP1. The inconsistencies of a proposed
      nucleotide insensitive H(+) transport by these UCPs as concluded from the
      expression in yeast and Escherichia coli are elucidated. In both expression
      system UCP 2 and 3 are not in or cannot be converted to a functionally native
      state and thus also for these UCPs a nucleotide regulated H (+) transport is
      postulated.

PMID- 11239491
TI  - Mitochondrial proton leak and the uncoupling protein 1 homologues.
AB  - Mitochondrial proton leak is the largest single contributor to the standard
      metabolic rate (SMR) of a rat, accounting for about 20% of SMR. Yet the
      mechanisms by which proton leak occurs are incompletely understood. The available
      evidence suggests that both phospholipids and proteins in the mitochondrial inner
      membrane are important determinants of proton conductance. The uncoupling protein
      1 homologues (e.g. UCP2, UCP3) may play a role in mediating proton leak, but it
      is unlikely they account for all of the observed proton conductance. Experimental
      data regarding the functions of these proteins include important ambiguities and
      contradictions which must be addressed before their function can be confirmed.
      The physiological role of the proton leak, and of the uncoupling protein 1
      homologues, remains similarly unclear.

PMID- 11239492
TI  - Mitochondrial efficiency: lessons learned from transgenic mice.
AB  - Metabolic research has, like most areas of research in the life sciences, been
      affected dramatically by the application of transgenic technologies. Within the
      specific area of bioenergetics it has been thought that transgenic approaches in
      mice would provide definitive proof for some longstanding metabolic theories and
      assumptions. Here we review a number of transgenic approaches that have been used
      in mice to address theories of mitochondrial efficiency. The focus is largely on
      genes that affect the coupling of energy substrate oxidation to ATP synthesis,
      and thus, mice in which the uncoupling protein (Ucp) genes are modified are
      discussed extensively. Transgenic approaches have indeed provided proof-of
      concept in some instances, but in many other instances they have yielded results
      that are in contrast to initial hypotheses. Many studies have also shown that
      genetic background can affect phenotypic outcomes, and that the upregulated
      expression of genes that are related to the modified gene often complicates the
      interpretation of findings.

PMID- 11239493
TI  - Repression of cytochrome P450 1A1 gene expression by oxidative stress: mechanisms
      and biological implications.
AB  - Cytochrome P450 1A1 (CYP1A1) is a member of a multigenic family of xenobiotic
      metabolizing enzymes. Beyond its usual role in the detoxification of polycyclic
      aromatic compounds, the activity of this enzyme can be deleterious since it can
      generate mutagenic metabolites and oxidative stress. The CYP1A1 gene is highly
      inducible by the environmental contaminants dioxin and benzo[a]pyrene. We discuss
      here the regulatory mechanisms that limit this induction. Several feedback loops
      control the activation of this gene and the subsequent potential toxicity. The
      oxidative repression of the CYP1A1 gene seems to play a central role in these
      regulations. The transcription factor Nuclear Factor I/CCAAT Transcription Factor
      (NFI/CTF), which is important for the transactivation of the CYP1A1 gene
      promoter, is particularly sensitive to oxidative stress. A critical cysteine
      within the transactivating domain of NFI/CTF appears to be the target of
      H(2)O(2). The DNA-binding domains of several transcription factors have been
      described as targets of oxidative stress. However, recent studies described here
      suggest that more attention should be given to transactivating domains that may
      represent biologically relevant redox targets of cellular signaling.

PMID- 11239494
TI  - Ca(2+)-dependent production of reactive oxygen metabolites by human neutrophils
      in response to fluorinated propranolol analogues.
AB  - Fluorinated analogues of propranolol, namely trifluoroethyl propranolol (F3),
      pentafluoropropyl propranolol (F5), and heptafluorobutyl propranolol (F7), were
      found to induce reactive oxygen metabolite (ROM) production in human neutrophils
      in a dose-dependent manner. Preincubation of neutrophils with the calcium
      chelator BAPTA-AM or the tyrosine kinase inhibitor genistein inhibited this ROM
      production. Direct measurements of intracellular calcium revealed that these
      analogues caused a transient increase in intracellular calcium. In addition,
      these fluorinated analogues of propranolol caused a transient increase in actin
      polymerization. The effects of these compounds were found to be dependent upon
      the degree of fluorination of the parent compound. Propranolol, on the other
      hand, had no direct effect on ROM, calcium, or actin polymerization when added
      alone to neutrophils, although it did modify responses of cells to various
      stimuli. Whereas ROM production induced by the chemotactic peptide formyl
      methionyl-leucyl-phenylalanine was enhanced in a dose-dependent manner, the
      response to the particulate stimulus, latex beads, was abolished.

PMID- 11239495
TI  - Specific desensitization of sulfonylurea- but not imidazoline-induced insulin
      release after prolonged tolbutamide exposure.
AB  - Functional effects of prolonged exposure to the sulfonylurea, tolbutamide, were
      examined in the clonal electrofusion-derived BRIN-BD11 cell line. In acute 20-min
      incubations, 50-400 microM tolbutamide stimulated a dose-dependent increase (P <
      0.01) in insulin release at both non-stimulatory (1.1 mM) and stimulatory (8.4
      mM) glucose. Culture with 100 microM tolbutamide (18 hr) caused a marked (67%)
      decrease in subsequent insulin-secretory responsiveness to acute challenge with
      200 microM tolbutamide, though notably, tolbutamide culture exerted no influence
      on 200 microM efaroxan-induced insulin secretion. Duration of exposure (3-18 hr)
      to 100 microM tolbutamide in culture also time-dependently influenced subsequent
      responsiveness to acute tolbutamide challenge, with progressive 47-58% decreases
      from 6-18 hr (P < 0.001). Similarly, 6- to 18-hr culture with 100 microM efaroxan
      specifically desensitized efaroxan-induced insulin release. Tolbutamide- and
      efaroxan-induced desensitization exhibited a time-dependent reversibility, with a
      sustained return to full insulin-secretory responsiveness by 12 hr. Notably, 18
      hr culture with tolbutamide or efaroxan did not significantly affect
      insulinotropic responses to 16.7 mM glucose, 10 mM 2-ketoisocaproic acid, 10 mM
      alanine, 10 mM arginine, or 30 mM KCl. Diverse inhibitory actions of tolbutamide
      or efaroxan culture on late events in stimulus-secretion coupling reveal that
      drug desensitization is both a specific and important phenomenon. As such, the
      model system described could prove an important tool in determining the complex
      modes of action of established and novel clinically useful insulinotropic
      compounds.

PMID- 11239496
TI  - Determination of in vivo adducts of disulfiram with mitochondrial aldehyde
      dehydrogenase.
AB  - Extensive use for disulfiram (DSF) has been found in the aversion therapy
      treatment of recovering alcoholics. Although it is known to irreversibly inhibit
      hepatic aldehyde dehydrogenase (ALDH), the specific mechanism of in vivo
      inhibition of the enzyme by the drug has not been determined yet. We have
      demonstrated in this report a novel, but simple and rapid method for structurally
      characterizing in vivo derived protein-drug adducts by linking on-line sample
      processing to HPLC-electrospray ionization mass spectrometry (HPLC-MS) and HPLC
      tandem mass spectrometry (HPLC-MS/MS). Employing this approach, rats were
      administered DSF, and their liver mitochondria were isolated and solubilized.
      Both native and in vivo DSF-treated mitochondrial ALDH (mALDH) were purified in
      one step with an affinity cartridge. The in vivo DSF-treated mALDH showed 77%
      inhibition in enzyme activity as compared with that of the control. Subsequently,
      the control and DSF-inhibited mALDH were both subjected to HPLC-MS analyses. We
      were able to detect two adducts on DSF-inhibited mALDH, as indicated by the mass
      increases of approximately 71 and approximately 100 Da. To unequivocally
      determine the site and structure of these adducts, on-line pepsin digestion-HPLC
      MS and HPLC-MS/MS were performed. We observed two new peptides at MH(+) = 973.7
      and MH(+) = 1001.8 in the pepsin digestion of DSF-inhibited enzyme. These two
      peptides were subsequently subjected to HPLC-MS/MS for sequence determination.
      Both peptides possessed the sequence FNQGQC(301)C(302)C(303), derived from the
      enzyme active site region, and were modified at Cys(302) by N-ethylcarbamoyl (+71
      Da) and N-diethylcarbamoyl (+99 Da) adducts. These findings indicated that N
      dealkylation may be an important step in DSF metabolism, and that the inhibition
      of ALDH occurred by carbamoylation caused by one of the DSF metabolites, most
      likely S-methyl-N,N-diethylthiocarbamoyl sulfoxide (MeDTC-SO). Finally, there was
      no evidence of the presence of an intramolecule disulfide bridge modification on
      the peptide FNQGQCCC.

PMID- 11239497
TI  - Inhibitory effect of alpha-lipoic acid and its positively charged amide analogue
      on nitric oxide production in RAW 264.7 macrophages.
AB  - The aim of this study was to investigate the effect of the mitochondrial cofactor
      alpha-lipoic acid [R (+) LA] or its lipoamide analogue, 2-(N,N-dimethylamine)
      ethylamido lipoate [R (+) LA-plus], on nitric oxide (NO) production in RAW 264.7
      macrophages. NO production from RAW 264.7 cells stimulated with 10 microg/mL of
      lipopolysaccharide and 50 U/mL of interferon-gamma was measured directly by
      electron spin resonance using spin-trapping techniques. R (+) LA or R (+) LA-plus
      was found to inhibit NO production at pharmacologically relevant concentrations.
      However, in a cell-free chemical system, neither R (+) LA nor R (+) LA-plus was
      able to directly scavenge NO. Furthermore, in the presence of 2.5 or 25 mM
      glucose, the inhibitory effects of R (+) LA and R (+) LA-plus on NO production
      were decreased markedly, while they showed more potent inhibitory effects in the
      presence of 2 microM rotenone or 5 microg/mL of antimycin A, inhibitors of
      mitochondrial complex I and complex III, respectively. Glucose, rotenone, or
      antimycin A alone resulted in an increase of NO production. These results suggest
      that NO production in macrophages can be regulated by glucose and mitochondrial
      respiration, and that modulation of NO production by lipoic acid or lipoamide
      analogues in inflammatory situations is attributed not to their radical
      scavenging activity but to their redox properties.

PMID- 11239498
TI  - Differential sensitivities of the MRP gene family and gamma-glutamylcysteine
      synthetase to prooxidants in human colorectal carcinoma cell lines with different
      p53 status.
AB  - 1Recent molecular cloning studies have identified six members in the multidrug
      resistance protein (MRP) gene family. However, the regulation of expression of
      these genes is largely unknown. We previously reported that expression of MRP1,
      encoding multidrug-resistance associated protein, and gamma-GCSh, which encodes
      the heavy subunit of gamma-glutamylcysteine synthetase (gamma-GCS), could be up
      regulated by prooxidants [Yamane et al., J Biol Chem 1998;273:31075-85]. In the
      present study, we investigated whether different members of the MRP family
      exhibit different responses to induction by prooxidants, and whether p53 status
      influences the levels of induction. A panel of colorectal cancer cell lines with
      different p53 status, i.e. HCT116 containing wild-type p53, and HT29, SW480, and
      Caco2 containing mutant p53, was treated with tert-butylhydroquinone (t-BHQ) and
      pyrrolidinedithiocarbamate (PDTC). MRP1 and gamma-GCSh mRNA levels were
      determined by the RNase protection assay, using gene-specific probes. We report
      here that induction of MRP1 and gamma-GCSh expression by these prooxidants varied
      among the different cell lines, and p53 mutations were not always associated with
      elevated levels of induction. These results suggest that the effects of p53 on
      the induced expression of MRP1 and gamma-GCSh depend on the environment of the
      cell and/or nature of p53 mutations. In an isogenic HCT116 cell line containing
      p53(-/-) alleles, we demonstrated that, as for MRP1, expression of MRP2 and MRP3
      was induced by the prooxidants, whereas expression of MRP4 and MRP5 was not. MRP6
      mRNA was not detectable. Induction of MRP2 expression by prooxidants seemed to be
      independent of p53 status. Our results demonstrated the differential regulation
      of the MRP gene family by p53 mutation under oxidative stress.

PMID- 11239499
TI  - Comparative effects of indomethacin on cell proliferation and cell cycle
      progression in tumor cells grown in vitro and in vivo.
AB  - Considerable research effort is currently being directed towards understanding
      the mechanisms mediating the antiproliferative effects of non-steroidal anti
      inflammatory drugs (NSAIDs) and, more recently, of cyclooxygenase (COX)-2
      inhibitors as well. A key question is whether NSAIDs (excluding sulindac) exert
      their anticarcinogenic effects in vivo by a mechanism that is dependent on their
      capacity to inhibit COX activity. Some studies with cultured tumor cells in vitro
      have argued against such a linkage, showing that NSAIDs inhibit cell replication
      and/or augment apoptosis only at concentrations that exceed those required to
      inhibit COX activities 10- to 100-fold. The significance of these results for the
      observed anticarcinogenic effects of NSAIDs in vivo has not yet been evaluated.
      We addressed this question by comparing, for the same tumor cells, the effects of
      the NSAID indomethacin on cell growth parameters when the cells were grown in
      culture to the effects seen in the in vivo growing tumor in the mouse.
      Indomethacin added to cultured Lewis lung carcinoma cells exerted a potent
      antiproliferative effect ((3)H thymidine assay) and reduced cell viability (MTT[3
      (4,5-dimethyl(thiazol-2-yl)-2,5 diphenyl tetrazolium bromide] assay) at low doses
      (10-20 microM) in parallel with its inhibitory effect on cellular cyclooxygenase.
      These effects of indomethacin appeared to arise from a clear antiproliferative
      shift in the profile of the cell cycle parameters towards a reduced percentage of
      cells at the S and G(2)/M phases, together with an increased percentage of cells
      at the G(1) phase. Significantly, similar results were seen when indomethacin was
      given in vivo at the low dose of 2 mg per kg/day, which blocked blood platelet
      COX activity and at the same time produced a delay in tumor growth initiation and
      attenuation of apparent primary tumor growth as well as growth of lung
      metastases. These results thus provide strong support for the notion that COX
      inhibition is a major determinant in the antitumorigenic effect of indomethacin
      in vivo.

PMID- 11239500
TI  - Ultrastructural morphology and localisation of cisplatin-induced platinum-DNA
      adducts in a cisplatin-sensitive and -resistant human small cell lung cancer cell
      line using electron microscopy.
AB  - Ultrastructural morphology (transmission electron microscopy) and localisation of
      cisplatin-induced platinum (Pt)-DNA adducts (immunoelectron microscopy) were
      analysed in the human small cell lung cancer cell line GLC(4) and its 40-fold in
      vitro acquired cisplatin-resistant subline GLC(4)-CDDP, which is characterised
      by, among other things, a decreased DNA platination. Immunolabelling of Pt-DNA
      adducts was performed with the polyclonal antibody GPt, known to detect the main
      Pt-containing intrastrand and interstrand DNA adducts. Morphological analysis of
      GLC(4) and GLC(4)-CDDP at the ultrastructural level showed cells with a high
      nucleus/cytoplasm ratio with the majority of nuclei containing one or more
      nucleoli. GLC(4)-CDDP showed, in contrast to GLC(4), an extensive Golgi apparatus
      and an increased number of mitochondria. DNA platination was detectable in both
      GLC(4) and GLC(4)-CDDP. Immunoelectron microscopy showed Pt-DNA adducts primarily
      in the nucleus, preferentially at loci with high-density chromatin (e.g.
      heterochromatin, pars granulosa around nucleoli, condensed DNA in proliferating
      and apoptotic cells), and in mitochondria. The level of detectable Pt-DNA adducts
      was cell cycle status-dependent. In both cell lines, Pt-DNA adduct levels
      increased from non-dividing interphase cells to dividing cells and were highest
      in cells undergoing apoptosis. Overall localisation of Pt-DNA adducts was
      comparable in GLC(4) and GLC(4)-CDDP cells.

PMID- 11239502
TI  - Ajoene, a natural product with non-steroidal anti-inflammatory drug (NSAID)-like
      properties?
AB  - The inducible isoform of cyclooxygenase (COX-2) is implicated in the pathogenesis
      of various inflammatory diseases as well as in carcinogenesis, especially of
      gastrointestinal tumors. Epidemiological as well as experimental data support a
      role for constituents of allium vegetables, such as garlic and onions, in the
      prevention of gastrointestinal cancer. Therefore, the aim of the present study
      was to examine whether the garlic-derived natural product ajoene interferes with
      the COX-2 pathway by using lipopolysaccharide (LPS)-activated RAW 264.7 cells as
      in vitro model. Ajoene was shown to dose-dependently inhibit the release of LPS
      (1 microg/mL)-induced prostaglandin E(2) in RAW 264.7 macrophages (IC(50) value:
      2.4 microM). This effect was found to be due to an inhibition of COX-2 enzyme
      activity by ajoene (IC(50) value: 3.4 microM). Ajoene did not reduce COX-2
      expression, but rather increased LPS-induced COX-2 protein and mRNA expression
      compared to LPS-stimulated cells only. In the absence of LPS, however, ajoene was
      unable to induce COX-2. The non-steroidal anti-inflammatory drug indomethacin was
      shown to act similarly in LPS-activated RAW 264.7 cells. These data suggest that
      ajoene works by a mechanism of action similar to that attributed to non-steroidal
      anti-inflammatory drugs. This finding may add a novel aspect to the biological
      profile of the garlic-derived natural product ajoene which might be important for
      understanding the usefulness of garlic for chemoprevention of gastrointestinal
      carcinomas.

PMID- 11239501
TI  - Adrenergic stimulation of osteoclastogenesis mediated by expression of osteoclast
      differentiation factor in MC3T3-E1 osteoblast-like cells.
AB  - It is well known that adrenergic agonists efficiently activate beta-adrenoceptors
      on osteoblastic cells and can stimulate bone resorption in intact mouse calvaria.
      Recently, an osteoclastogenic factor of osteoblastic origin was found to be a
      novel tumor necrosis factor ligand family member and was termed osteoclast
      differentiation factor (ODF). Using a reverse transcription-polymerase chain
      reaction approach, we investigated the effect of epinephrine on mRNA levels of
      ODF and its decoy receptor, osteoclastogenesis inhibitory factor (OCIF), in MC3T3
      E1 cells. Treatment with epinephrine (1 microM) rapidly increased ODF and OCIF
      mRNA levels, which peaked after 0.5 hr of treatment. Epinephrine (1 microM) also
      increased interleukin (IL)-6, IL-11, and cyclooxygenase (COX)-II mRNA levels, as
      well as increased prostaglandin E(2) (PGE(2)) accumulation in the culture medium.
      Treatment of the cells with IL-11 (10 ng/mL) or PGE(2) (1 microM) increased ODF
      and OCIF mRNA levels as observed with epinephrine. However, increases in ODF and
      OCIF mRNA levels by epinephrine were more rapid than those by IL-11, and were not
      influenced by NS-398 (100 microM; an inhibitor of COX-II), suggesting a direct
      effect of epinephrine on ODF and OCIF mRNA expressions as well as an indirect
      effect mediated by IL-11 and PGE(2) production. Epinephrine-induced increases in
      ODF and OCIF mRNA levels were inhibited by pretreatment with timolol (1 microM;
      beta-antagonist) and phentolamine (1 microM; alpha-antagonist), respectively.
      Furthermore, the formation of tartrate-resistant acid phosphatase-positive
      multinucleated cells from mouse bone marrow cells was stimulated by isoproterenol
      (0.1 to 10 microM) or epinephrine (0.1 to 10 microM). The action of
      isoproterenol, a beta-agonist, was clearly stronger than that of epinephrine,
      suggesting the importance of the physiological balance between ODF and OCIF
      productions for osteoclastogenesis. These findings suggest that beta-adrenergic
      stimulation induces not only IL-6, IL-11, and PGE(2) but also ODF expression in
      osteoblastic cells, leading to a stimulation of osteoclastogenesis.

PMID- 11239503
TI  - Conjugative metabolism of 1,2-dibromoethane in mitochondria: disruption of
      oxidative phosphorylation and alkylation of mitochondrial DNA.
AB  - 1,2-Dibromoethane (DBE) is an environmental contaminant that is metabolized by
      glutathione S-transferases to a haloethane-glutathione conjugate. Since
      haloethane-glutathione conjugates are known to alkylate nuclear DNA and
      cytoplasmic proteins, these effects were investigated in isolated rat liver
      mitochondria exposed to DBE by measuring guanine adducts and several aspects of
      oxidative phosphorylation including respiratory control ratios, respiratory
      enzyme activity, and ATP levels. Mitochondrial large-amplitude swelling and
      glutathione status were assessed to evaluate mitochondrial membrane integrity and
      function. When exposed to DBE, mitochondria became uncoupled rapidly, yet no
      large-amplitude swelling or extramitochondrial glutathione was observed.
      Mitochondrial GSH was depleted to 2-53% of controls after a 60-min exposure to
      micromolar quantities of DBE; however, no extramitochondrial GSH or GSSG was
      detected. The depletion of mitochondrial glutathione corresponded to an increase
      of an intramitochondrial GSH-conjugate which, based on HPLC elution profiles and
      retention times, appeared to be S,S'-(1,2-ethanediyl)bis(glutathione). Activities
      of the NADH oxidase and succinate oxidase respiratory enzyme systems were
      inhibited 10-74% at micromolar levels of DBE, with succinate oxidase inactivation
      occurring at lower doses. ATP concentrations in DBE-exposed mitochondria in the
      presence of succinate were 5-90% lower than in the controls. The DNA adduct S-[2
      (N(7)-guanyl)ethyl]glutathione was detected by HPLC in mtDNA isolated from DBE
      exposed mitochondria. The results suggest that respiratory enzyme inhibition,
      glutathione depletion, decreased ATP levels, and DNA alkylation in DBE-exposed
      mitochondria occur via the formation of an S-(2-bromoethyl)glutathione conjugate,
      the precursor of the episulfonium ion alkylating species of DBE.

PMID- 11239504
TI  - Regulation of transcription of the glutathione S-transferase P1 gene by
      methylation of the minimal promoter in human leukemia cells.
AB  - To study the relationship between methylation and the transcriptional activity of
      the minimal promoter of the glutathione S-transferase GSTP1 gene encoding
      glutathione S-transferase P1-1, GSTP1 mRNA levels as well as basal promoter
      activity were compared in human leukemia cell lines. The K562 erythroleukemia
      cell line presented a strong GSTP1 promoter activity, as measured in transient
      transfection assays using a luciferase reporter plasmid, and correlated with a
      high mRNA whereas in Raji cells no mRNA was expressed. In order to establish a
      relationship between the expression and the methylation status, we used in vitro
      bisulfite sequencing which indicated that both methylated and unmethylated GSTP1
      promoter alleles coexisted in K562 cells, whereas Raji lymphoma cells showed a
      nearly uniform hypermethylation of the promoter region. To determine the impact
      of methylation, we used in vitro SssI methylation of the minimal GSTP1 promoter,
      which led to the silencing of the promoter activity in transient transfection
      assays in expressing K562 as well as in non-expressing Raji cells. These data are
      in good agreement with previously obtained results and indicate that methylation
      of CpG sites of the basal promoter is an essential mechanism in the control of
      GSTP1 gene expression in human leukemia.

PMID- 11239505
TI  - Effects of melanocortin peptides on lipopolysaccharide/interferon-gamma-induced
      NF-kappaB DNA binding and nitric oxide production in macrophage-like RAW 264.7
      cells: evidence for dual mechanisms of action.
AB  - The pro-opiomelanocortin-derived peptide alpha-melanocyte-stimulating hormone
      (alpha-MSH) mediates broad anti-inflammatory and immunomodulatory effects, which
      include inhibition of the production and release of proinflammatory cytokines and
      nitric oxide (NO) from macrophages. We investigated the effects of alpha-MSH,
      alpha-MSH(1-10), and alpha-MSH(11-13) on NO production and nuclear factor-kappaB
      (NF-kappaB) translocation in RAW 264.7 macrophages. After stimulation of the
      cells with bacterial lipopolysaccharide/interferon-gamma (LPS/IFN-gamma), all
      three peptides inhibited NO production with an order of potency alpha-MSH > or =
      alpha-MSH(11-13) > alpha-MSH(1-10). All three MSH peptides inhibited NF-kappaB
      nuclear translocation with the maximal effect of alpha-MSH and alpha-MSH(11-13)
      being seen in the range 1 nM-1 microM, and that of alpha-MSH(1-10) at 1 microM.
      By use of (125)I-(Nle(4),D-Phe(7))alpha-MSH(NDP-MSH) radioligand binding, MC(1)
      receptor-binding sites were demonstrated on RAW 264.7 cells. alpha-MSH and alpha
      MSH(1-10) competed with the (125)I-NDP-MSH binding at these MC(1) receptor
      binding sites, but alpha-MSH(11-13) even in concentrations up to 1 mM did not.
      Moreover, alpha-MSH and alpha-MSH(1-10) caused powerful stimulation of cyclic
      3',5'-adenosine monophosphate (cAMP) in the RAW 264.7 cell, whereas alpha-MSH(11
      13) was ineffective. Forskolin stimulated cAMP and inhibited NO production to the
      same extent as alpha-MSH and alpha-MSH(1-10), but did not modify the
      translocation of NF-kappaB. Whereas the protein kinase A inhibitor H89 did not
      modify the effect of alpha-MSH on NF-kappaB translocation, H89 caused a partial
      inhibition of the inhibitory effect of alpha-MSH, alpha-MSH(1-10), alpha-MSH(11
      13), and forskolin on NO production. In addition alpha-MSH, alpha-MSH(1-10),
      alpha-MSH(11-13), and forskolin also inhibited the activity of an NF-kappaB
      dependent luciferase reporter and these effects were partially counteracted by
      H89. We suggest that melanocortin peptides act via dual mechanisms of action: one
      cAMP-independent and causing inhibition of NF-kappaB translocation and the other
      dependent on MC(1) receptor/cAMP activation.

PMID- 11239506
TI  - Physiological evidence for a P2Y receptor responsive to diadenosine
      polyphosphates in human lung via Ca(2+) release studies in bronchial epithelial
      cells.
AB  - P2Y(2) receptors that are activated by the extracellular nucleotides ATP or UTP
      mediate Cl(-) secretion via an increase in [Ca(2+)](i) (intracellular calcium
      concentration). Therefore, in the lung of patients suffering from cystic
      fibrosis, inhalation of aerosolized UTP offers a way to circumvent the defect in
      Cl(-) secretion by the cystic fibrosis transmembrane conductance regulator. A
      possible alternative for the relatively unstable UTP in inhalation therapy is the
      more resistant diadenosine tetraphosphate (Ap(4)A). In human and rat lung
      membranes, Ap(4)A binds to P2 receptor sites coupled to G proteins. Here, we
      showed that Ap(4)A caused an increase in [Ca(2+)](i) with an EC(50) of 17 microM
      in human bronchial epithelial cells (HBE1). The [Ca(2+)](i) rise evoked by ATP
      and UTP was completely, but that induced by Ap(4)A only partially, caused by
      release of Ca(2+) from internal stores. Moreover, the potency of Ap(4)A to
      mobilize Ca(2+) was lower than that of ATP and UTP (EC(50) 1.5 and 1.8 microM,
      respectively), and the maximal increase in [Ca(2+)](i) was considerably smaller
      than that after ATP or UTP. In accordance with our previous results providing
      evidence for a common binding site for various diadenosine polyphosphates in lung
      membranes, all Ap(n)A analogues tested (n = 3 to 6) caused a comparable
      [Ca(2+)](i) increase. Homologous or heterologous prestimulation largely
      diminished the increase in [Ca(2+)](i) found after a second pulse of either UTP
      or Ap(4)A. Although specific binding characteristics and functional responses of
      Ap(4)A on lung cells are in favor of a distinct receptor for Ap(4)A, the cross
      talk between UTP and Ap(4)A in HBE1 cells and the only slight differences in
      Ca(2+) mobilization by ATP or UTP and Ap(4)A render it impossible at this point
      to state unequivocally whether there exists a distinct P2Y receptor specific for
      diadenosine polyphosphates in lung epithelia or whether Ap(4)A activates one of
      the nucleotide receptors already described.

PMID- 11239508
TI  - The clinical validation of novel strategies for monitoring transplant recipients.
AB  - In the early postoperative period after solid organ transplantation, the patient
      is monitored intensively to detect the early development of surgical and
      infectious complications or allograft rejection. Laboratory tests form an
      essential component of the routine monitoring protocol-particularly those that
      are of diagnostic value in assessing graft function. In this paper, we illustrate
      how a new liver-function test, alpha-glutathione S-transferase immunoassay, was
      subjected to systematic technical and clinical evaluation in the liver-transplant
      population, including a randomized, controlled trial that provided the evidence
      for its introduction into the routine laboratory. We also illustrate how the
      carefully controlled monitoring in a clinical trial is difficult to reproduce
      under routine circumstances and the crucial role of audit in ensuring that
      recommendations governing the use of a new diagnostic test are adhered to in
      clinical practice. Finally, we describe an "equivalence study," whereby our
      rigorous validation of the alpha-glutathione S-transferase assay has enabled us
      to fast-track the development of a simpler and cheaper liver function test
      (fructose 1,6-bisphosphatase), which shares similar diagnostic characteristic to
      alpha-glutathione S-transferase, without the requirement for a further clinical
      trial.

PMID- 11239509
TI  - New developments in the immunosuppressive drug monitoring of cyclosporine,
      tacrolimus, and azathioprine.
AB  - The calcineurin inhibitors cyclosporine and tacrolimus form the cornerstones of
      most immunosuppression protocols. Because of their variable pharmacokinetics, and
      their narrow therapeutic indices, post-transplant immunosuppressive drug
      monitoring is an essential part of patient care to minimize the risks of toxicity
      or acute rejection. Furthermore, a reduction in the rate of acute rejection has
      been shown to result in a lower rate of graft loss due to chronic rejection. The
      introduction of the microemulsion formulation of cyclosporine with its more
      consistent bioavailability has renewed interest in the use of alternative
      sampling strategies to the trough cyclosporine concentration. Both
      pharmacokinetic and pharmacodynamic considerations support the concept that
      determination of cyclosporine during the absorption phase (0-4 h) might offer a
      better prediction of cyclosporine immunosuppressive efficacy. Initial
      investigations suggest that monitoring a 2-h postdose concentration C(2) may
      provide a more efficacious alternative to trough monitoring for optimizing
      therapy with Neoral. Tacrolimus has a 10- to 100-fold greater in vitro
      immunosuppressive activity compared with cyclosporine. Consistent with its
      greater potency, therapeutic whole blood trough concentrations for tacrolimus are
      around 20-fold lower than the corresponding cyclosporine concentrations. The
      correlation between toxicity and tacrolimus trough concentrations appears to be
      stronger than that for acute rejection. The results from a concentration-ranging
      trial in primary kidney-transplantation and liver-transplantation trials all
      found a significant relationship between toxicity and tacrolimus trough levels.
      Azathioprine is converted in vivo to 6-mercaptopurine, which is subsequently
      metabolized to the pharmacologically active 6-thioguanine nucleotides. The latter
      are also responsible for the cytotoxic side effects. Reliance on blood counts to
      monitor azathioprine therapy can be misleading, and they do not provide
      information on immunosuppresive efficacy. More pertinent information can be
      obtained through the measurement of thiopurine S-methyltransferase activity and
      the quantification of intracellular 6-thioguanine nucleotides concentrations in
      red blood cells. Prospective studies have demonstrated the clinical utility of
      determining 6-thioguanine nucleotides to individualise immunosuppressive therapy
      with azathioprine not only in the field of transplantation, but also in
      inflammatory bowel disease.

PMID- 11239510
TI  - Pharmacokinetic, pharmacodynamic, and outcome investigations as the basis for
      mycophenolic acid therapeutic drug monitoring in renal and heart transplant
      patients.
AB  - Mycophenolate mofetil is widely used in combination with either cyclosporine or
      tacrolimus for rejection prophylaxis in renal and heart transplant patients.
      Although not monitored routinely nearly to the degree that other agents such as
      cyclosporine or tacrolimus, there is an expanding body of experimental evidence
      for the utility of monitoring mycophenolic acid, the primary active metabolite of
      mycophenolate mofetil, plasma concentration as an index of risk for the
      development of acute rejection. The following are important experimentally-based
      reasons for recommending the incorporation of target therapeutic concentration
      monitoring of mycophenolic acid: (1) the MPA dose-interval area-under-the
      concentration-time curve, and less precisely, MPA predose concentrations predict
      the risk for development of acute rejection; (2) the strong correlation between
      mycophenolic acid plasma concentrations and expression of important cell surface
      activation antigens, whole blood pharmacodynamic assays of lymphocyte
      proliferation and median graft rejection scores in a heart transplant animal
      model; (3) the greater than 10-fold interindividual variation of MPA area under
      the concentration time curve values in heart and renal transplant patients
      receiving a fixed dose of the parent drug; (4) drug-drug interactions involving
      other immunosuppressives are such that when switching from one to another (eg,
      from cyclosporine to tacrolimus or vice-versa) substantial changes in MPA
      concentrations can occur in patients receiving a fixed dose of the parent drug;
      (5) significant effects of liver and kidney diseases on the steady-state total
      and free mycophenolic acid area under the concentration time curve values; (6)
      the need to closely monitor mycophenolic acid when a major change in
      immunosuppression is planned such as steroid withdrawal. Current investigations
      are focused on determination of the most optimal sampling time and for
      mycophenolic acid target therapeutic concentration monitoring. Further
      investigations are needed to evaluate the pharmacologic activity of the newly
      described acyl glucuronide metabolite of mycophenolic acid which has been shown
      to inhibit, in vitro, inosine monophosphate dehydrogenase.

PMID- 11239511
TI  - Monitoring xenotransplant recipients for infection by PERV.
AB  - OBJECTIVES: Concerns have been raised over the possibility of transmission of
      porcine endogenous retrovirus (PERV) to porcine xenograft recipients. METHODS: To
      help assess this risk, diagnostic assays capable of detection of an active,
      latent or cleared PERV infection, and the presence of pig cell microchimerism
      have been developed by a number of groups. Retrospective studies of patients
      exposed to living pig tissues have been performed using these assays to look for
      evidence of cross species transmission. RESULTS: To date no evidence of PERV
      infection has been found in studies of humans exposed to pig tissues, despite
      evidence of long lived microchimerism. CONCLUSIONS: These data suggest that PERV
      infection has not occurred in a clinical setting. However, as infection has been
      seen in a small animal model further investigation of the risk from PERV is
      warranted.

PMID- 11239512
TI  - Cellular and molecular parameters in human renal allograft rejection.
AB  - Acute rejection of human renal allografts is frequent postransplantation
      complication. In addition, it is a risk factor for chronic rejection, the most
      common cause of failure of long-term allografts. Renal allografts are rejected as
      a result of an immune response directed against alloantigens on the graft that
      are absent from the host, and the most important of these are the HLA antigens.
      The application of molecular diagnostic methods has revealed a differential intra
      renal gene expression of cytokines, chemokines and their receptors, and cytotoxic
      attack molecules in acute and chronic rejection processes. Differential
      expression of T cell costimulatory molecules B7 and CD40/CD40L, and endothelium
      adhesion molecules ICAM-1 and VCAM-1 has also been reported during acute
      rejection. These molecules play an important role in mediating the recruitment of
      lymphocytes into rejecting allografts and costimulation of T cell activation.
      Based on experimental data, it seems that it is likely that the blockade of T
      cell costimulatory pathways can be used in human in the future to selectively
      prevent transplant rejection without generally suppressing the immune system.

PMID- 11239513
TI  - Hypersialylated macromolecular serum immunoglobulin A1 in type 2 diabetes
      mellitus.
AB  - OBJECTIVES: The origin of the elevation of serum immunoglobulin A1 (IgA1) in Type
      2 diabetes mellitus (DM) is unsettled. The aim of this study was to address the
      carbohydrate changes of serum IgA1 from patients with Type 2 diabetes mellitus,
      as a possible cause of the elevation. DESIGN AND METHODS: IgA1 was purified from
      sera of 6 DM patients and 4 healthy matched controls by using highly acetylated
      Sepharose 6B, anti-IgA-agarose, and jacalin-agarose columns, and further
      separated into jacalin low-affinity, medium, and high-affinity fractions. Hinge
      and Fc fragments from native IgA1 were obtained and analyzed by using Sambucus
      nigra, Maackia amurensis, Arachis hypogaea, Erythrina cristagalli, and Ricinus
      communis lectins. RESULTS: The jacalin high-affinity fraction, mostly constituted
      by macromolecular IgA1, was more abundant in DM patients than in controls and
      also more reactive to Sambucus nigra, and Maackia amurensis lectins. CONCLUSIONS:
      Macromolecular serum IgA1 from DM patients is hypersialylated and this probably
      contributes to the high level of IgA1 in DM patients.

PMID- 11239514
TI  - Sensitive method for nontransferrin-bound iron quantification by graphite furnace
      atomic absorption spectrometry.
AB  - OBJECTIVE: To establish a sensitive method for measuring nontransferrin-bound
      iron (NTBI) in serum samples using graphite furnace atomic absorption
      spectrometry (GFAAS). DESIGN AND METHODS: Nontransferrin-bound iron (NTBI) was
      chelated using nitrilotriacetic acid (NTA) and then ultrafiltered according to
      the method employed by Singh et al. [1]. Serum ultrafiltrates were diluted
      eightfold with distilled water. NTBI from the Fe-NTA complex present in the serum
      ultrafiltrate was measured using GFAAS. RESULTS: Nontransferrin-bound iron (NTBI)
      and other parameters were measured in seven patients diagnosed with hereditary
      hemochromatosis by liver biopsy. Total serum iron, NTBI and transferrin
      saturation values (ranging from 87% to 90%) were elevated for three of the seven
      hemochromatosis patients tested before therapeutic phlebotomy. Six of the seven
      hemochromatosis patients had undergone phlebotomy and revealed normal total serum
      iron, NTBI and transferrin saturation values. Nine test subjects (not diagnosed
      with hemochromatosis) with abnormally high total serum iron and/or ferritin
      concentrations exhibited normal NTBI values (< or =0.14 micromol/L to 0.29
      micromol/L). The detection limit was 0.1 micromol/L for a 25 microL injection
      volume. CONCLUSIONS: The GFAAS method presented here provides a sensitive assay
      to quantitate NTBI in serum samples. The method developed is 4 to 5 times more
      sensitive than the only other GFAAS method [2] and more than an order of
      magnitude more sensitive than other colorimetric methods [1,3]. Improvement in
      sensitivity over the other GFAAS method [2] may be accounted for by differences
      in sample preparation between this method and that of Nielsen et al. [2]. Serum
      ultrafiltrates in this study were diluted eightfold with distilled water and
      mixed with a magnesium nitrate matrix modifier before GFAAS analysis. NTBI
      results obtained from this study indicate that the plasma iron pool in
      hemochromatosis patients awaiting phlebotomy increases to a level at which
      transferrin's ability to bind iron becomes exhausted and elevated NTBI levels
      appear in the serum. NTBI can mediate the production of reactive oxygen species
      and may cause organ damage associated with iron overload.

PMID- 11239515
TI  - Short-term variability in the measurement of plasma homocysteine, fasting and
      post-methionine loading.
AB  - OBJECTIVES: Hyperhomocysteinemia is associated with premature cerebral,
      peripheral and coronary vascular disease. Evaluation of the significance of
      changes in plasma total homocysteine (tHcy) results obtained by analysis of
      serial specimens may be accomplished only by taking into account biologic
      (between-person and within-person) as well as analytical variation. Since the
      repeatability of a measurement significantly determines our ability to associate
      tHcy level with the presence of disease, this study was performed to evaluate
      various components of variation in tHcy values. DESIGN AND METHODS: We report the
      within-person, between-person, and methodological variability of tHcy, both
      fasting and postmethionine load (PML) values, in 20 healthy volunteers from whom
      samples were drawn weekly for 4 weeks. RESULTS: The short-term reliability
      coefficient (R) was 0.72 for fasting tHcy and 0.83 for PML tHcy. CONCLUSIONS: The
      current study demonstrates for the first time that the short-term reliability
      coefficient for PML tHcy is relatively high (0.83), suggesting that an
      individual's PML tHcy, like fasting tHcy, is relatively constant over at least
      one month, and that a single measurement should provide a reasonable
      characterization of an individual's PML tHcy concentration.

PMID- 11239516
TI  - Preliminary report on the effect of xenoperfusion with human blood on cyclosporin
      A metabolism and cytochrome-P-4503A4-mRNA expression in a pig liver perfusion
      model.
AB  - OBJECTIVES: Little is known about the effect of ischemia/reperfusion with
      xenogenic blood on function and gene expression of CYP3A4, the enzyme largely
      responsible for the metabolism of the immunosuppressants Cyclosporin A (CsA) and
      Tacrolimus. DESIGN AND METHODS: In a pig liver perfusion model, we have compared
      the effect of perfusion (3 h) after 20 h cold storage, with either pig or human
      blood on CsA metabolism and CYP3A4-mRNA expression. mCYP3A4-mRNA was quantified
      by RT-PCR, CsA and its major metabolites AM1, AM9, AM4N by RP-HPLC. IL-6 served
      as inflammation marker, GLDH and ALT to estimate tissue damage. RESULTS:
      Inflammatory response and tissue damage were more extensive during xenoperfusion.
      CYP3A4 expression decreased similarly during xenogenic and allogenic perfusion.
      CsA conversion to its metabolites was also comparable during xeno- and
      alloperfusion. CONCLUSION: There is no evidence that during the early reperfusion
      period pig liver CYP3A4 is severely affected if the organ is xenoperfused with
      human blood in comparison with alloperfusion.

PMID- 11239517
TI  - The HLA-DQB alleles and amino acid variants of the vitamin D-binding protein in
      diabetic patients in Alsace.
AB  - BACKGROUND: The HLA-DQB1 chain, in particular the amino acid in position 57, and
      genetic variants of the vitamin D-binding protein (DBP) have been reported to be
      associated with type 1 diabetes. There are two known polymorphisms in exon 11 of
      the DBP gene resulting in amino acid variants: codons 416 GAT --> GAG (Asp -->
      Glu) and 420 ACG --> AAG (Thr --> Lys). We compared distribution of DQB1 alleles
      and amino acid variants of DBP in type 1 diabetic patients (n = 44) in the
      Alsacian population and in healthy controls (n = 58). METHODS: The second exon of
      the DQB1 gene and exon 11 of DBP were analyzed by restriction mapping after
      polymerase chain reaction. RESULTS: A significant enrichment in DQB1 alleles
      encoding for an amino acid different from Asp in position 57 (NA) was observed in
      diabetic subjects as compared to controls (94.3 vs. 32.8%; p < 0.001).
      Combinations other than Ala/Ala carried the highest relative risk (OR = 52; p <
      0.001). The analysis of the polymorphism in exon 11 of DBP showed a significant
      difference in the allele frequency of the HaeIII site, but not of the StyI site
      between patients and controls. Allele frequencies of HaeIII in diabetic subjects
      were 36% and 64% for Asp and Glu respectively (p < 0.001; chi(2) = 29.5). The
      frequency of Asp/Asp and Glu/Glu genotypes was increased in controls and diabetic
      subjects respectively. DBP alleles in individuals carrying the DQB1 NA
      combination revealed that 46.6% of diabetics were DBP Asp/Glu, but this was not
      statistically significant using the Fisher exact test (16/31 vs. 0/3; p = 0.23).
      CONCLUSIONS: The study of the DQB1 chain confirmed the value of alleles encoding
      for an amino acid different from Asp in position 57 (NA) in the susceptibility to
      type 1 diabetes. The allele frequency of the HaeIII site, but not of the StyI
      site, differed between patients and controls (HaeIII p < 0.001; StyI p > 0.05).

PMID- 11239518
TI  - Oxidative stress and nitric oxide related parameters in type II diabetes
      mellitus: effects of glycemic control.
AB  - OBJECTIVES: The aim of this study is to investigate the status of oxidative
      stress and nitric oxide related parameters in type II diabetes mellitus (DM)
      patients in which heart disease, atherosclerosis, retinopathy, and nephropathy
      commonly occur, and also to determine the effect of glycemic control on these
      parameters. DESIGN AND METHODS: Erythrocyte copper zinc-superoxide dismutase
      (CuZn-SOD), erythrocyte and plasma selenium dependent glutathione peroxidase (Se
      GPx), erythrocyte catalase (CAT) activities, erythrocyte and plasma
      thiobarbituric acid reactive substances (TBARS) levels; nitrite/nitrate (NO(2)(
      )/NO(3)(-)), cyclic guanosine monophosphate (cGMP) and nitrotyrosine levels in
      plasma of type II DM patients were measured. RESULTS: Erythrocyte CuZn-SOD
      activities in type II DM were significantly higher than those of the control
      subjects (p < 0.05). TBARS levels in type II DM were significantly higher than
      the control subjects (p < 0.001). Plasma NO(2)(-)/NO(3)(-) levels in type II DM
      patients both during poor glycemic control and after three months of oral
      antidiabetic treatment were significantly higher than those of the control
      subjects (p < 0.001). Plasma cGMP levels in type II DM patients during poor
      glycemic control were significantly lower than those of control subjects (p <
      0.001). CONCLUSION: These results indicate that oxidative status and nitric oxide
      metabolism are affected in type II DM patients. We found high CuZn-SOD activity
      in type II DM patients. This increased activity could not protect the patients
      against the reactive oxygen species (ROS), since lipid peroxidation (defined by
      erythrocyte and plasma TBARS levels) still occurs in DM patients. After the
      therapy with oral antidiabetic agents for three months, erythrocyte SE-GPx and
      CAT activities were found to be decreased below the control values. Our results
      suggested that the low cGMP levels in the study may be a good marker of
      endothelium dysfunction in DM.

PMID- 11239519
TI  - Role of lipids, lipoproteins and vitamins in women with breast cancer.
AB  - OBJECTIVES: Improper balance between the production of reactive oxygen
      metabolites (ROMs), and antioxidative defense system have been defined as
      oxidative stress in various pathologic conditions. Lipids, lipoproteins and
      antioxidative vitamins have been associated with the risk of breast cancer. The
      present case-control study was conducted to investigate the status of
      antioxidative vitamins (A, C and E), lipids (total cholesterol; TC and
      triglycerides; TG), lipoproteins (high-density lipoprotein cholesterol; HDL-C and
      low-density lipoprotein cholesterol; LDL-C) and retinol-binding protein (RBP) in
      breast cancer patients. The aim of the study was to find out oxidative stress in
      breast cancer. DESIGN AND METHODS: Plasma lipids, lipoproteins and vitamins were
      estimated in 54 untreated breast cancer patients of different clinical stages and
      in 42 age- and sex-matched controls. RESULTS: Plasma TC (p < 0.05), and LDL-C and
      TG (p < 0.01) were found to be significantly elevated among breast cancer
      patients as compared to the controls. On the other hand, plasma HDL-C
      concentration (p < 0.001) and vitamin C and E (p < 0.01) were observed
      significantly decreased in breast cancer patients than in the controls. The
      maximum changes in plasma TC, and vitamin C and E concentrations were observed in
      breast cancer patients with stage IV when compared with controls. CONCLUSION: The
      study suggests that higher levels of TC and TG may play important role in
      carcinogenesis. Furthermore, the elevated plasma LDL-C concentration, which is
      more susceptible to oxidation, may result in higher lipid peroxidation in breast
      cancer patients. However, decreased concentrations of HDL-C and vitamin C and E
      are not likely to be sufficient enough to counter higher ROMs production reported
      earlier in breast cancer patients that may cause oxidative stress leading to
      cellular and molecular damage thereby resulting in cell proliferation and
      malignant conversions.

PMID- 11239520
TI  - A retrospective analysis of mycophenolic acid and cyclosporin concentrations with
      acute rejection in renal transplant recipients.
AB  - OBJECTIVES: Although monitoring of cyclosporin (CsA) is standard clinical
      practice postrenal transplantation, mycophenolic acid (MPA) concentrations are
      not routinely measured. There is evidence that a relationship exists between MPA
      area under the concentration-time curve (AUC) and rejection. In this study, a
      retrospective analysis was undertaken of 27 adult renal transplant recipients.
      METHODS: Patients received CsA and MPA therapy and had a four-point MPA AUC
      investigation. The relationship between MPA AUC performed in the first week after
      transplantation, as well as median trough cyclosporin concentrations, and
      clinical outcomes in the first month posttransplant were evaluated. RESULTS: A
      total of 12 patients experienced biopsy proven rejection (44.4%) and 4 patients
      had gastrointestinal adverse events (14.8%). A statistically significant
      relationship was observed between the incidence of biopsy proven rejection and
      both MPA AUC (p = 0.02) and median trough CsA concentration (p = 0.008). No
      relationship between trough MPA concentration and rejection was observed (p =
      0.21). Only 3 of 11 (27%) patients with an MPA AUC > 30 mg x h/L and a median
      trough CsA > 175 microg/L experienced acute rejection, compared with a 56%
      incidence of rejection for the remaining 16 patients. Patients who experienced
      adverse gastrointestinal events had significantly lower MPA AUC (p = 0.04), but
      median trough CsA concentrations were not significantly different (p = 0.24).
      Further, 3 of these 4 patients had rejection episodes. CONCLUSIONS: In addition
      to standard CsA monitoring, we propose further investigation of the use of a 4
      point sampling strategy to predict MPA AUC in the first week posttransplant,
      which may facilitate optimization of mycophenolate mofetil dose at a time when
      patients are most vulnerable to acute rejection.

PMID- 11239521
TI  - Urinary transferrin and albumin concentrations in patients with type 1 diabetes
      and normal controls: the search for the first protein lost.

PMID- 11239522
TI  - ACE gene polymorphism and long-term renal graft function.
AB  - OBJECTIVES: The long-term outcome of transplanted kidneys has not changed
      substantially and only a minority of grafts survives more than 15 yr. The aim of
      this study was to determine the influence of ACE gene polymorphism on long-term
      outcome after renal transplantation. DESIGN AND METHODS: Using PCR, we evaluated
      ACE I/D gene polymorphism in a group of patients with long-term graft function
      (LTF) over 15 yr and compared it with control groups of transplant recipients and
      population sample. RESULTS: The distribution of genotypes in the LTF group
      differed from transplant controls (p < 0.05). Moreover, DD homozygotes in the LTF
      group had better creatinine clearance (DD: 1.1 +/- 0.3, ID: 0.96 +/- 0.3, II:
      0.76 +/- 0.3 mL/s; p < 0.05). There were no differences in genotype distribution
      between transplant and population samples. CONCLUSIONS: Results of our study have
      demonstrated a possible connection between the DD variant of ACE I/D gene
      polymorphism and excellent long-term graft function.

PMID- 11239523
TI  - The emerging use of the 20-microg oral contraceptive.
AB  - OBJECTIVE: To highlight studies that investigated the efficacy, safety, and
      tolerability of low-dose oral contraceptives (OCs) containing 20 microg of
      ethinyl estradiol (EE) and to discuss the use of these low-dose contraceptives in
      women from adolescence to menopause and the noncontraceptive health benefits
      likely to be afforded by low-dose contraceptives. DESIGN: Relevant literature was
      identified by searching MEDLINE and EMBASE. Other sources were located by
      consulting the bibliographies of the material collected from Medline and EMBASE.
      Sources for additional information included documents from the United States Food
      and Drug Administration and the Physicians' Desk Reference (54th ed.).
      CONCLUSION(S): The current lowest available dose of EE used for OCs in the United
      States is 20 microg. Formulations with 20 microg of EE are efficacious and have a
      low incidence of estrogen-related side effects. Since this lowest effective EE
      dose inhibits ovarian activity, 20 microg of EE should also provide the
      noncontraceptive health benefits of OCs. Both contraceptive and noncontraceptive
      benefits of OCs are available to most women from adolescence to menopause without
      complications.

PMID- 11239524
TI  - Poor embryo quality: The answer lies (mostly) in the egg.

PMID- 11239525
TI  - DNA damage in patients with untreated cancer as measured by the sperm chromatin
      structure assay.
AB  - OBJECTIVE: To examine the relationship between sperm chromatin defects, evaluated
      by sperm chromatin structure assay (SCSA) and semen characteristics in
      cryopreserved semen specimens from patients diagnosed with various types of
      cancer. DESIGN: Prospective study. SETTING: Andrology laboratory at a tertiary
      care hospital. PATIENT(S): Cryopreserved semen samples from 12 healthy fertile
      men and 37 men diagnosed with cancer: testicular cancer (n = 20), Hodgkin's
      disease (n = 11), non-Hodgkin's disease (n = 4), and other neoplasm (n = 2).
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The shift of green (native DNA)
      to red (denatured, single-stranded DNA) fluorescence in acridine orange-stained
      nuclei was measured and quantified using the expression alpha(t)(red
      fluorescence/[red + green fluorescence] per cell). Sperm DNA damage was
      correlated with classical semen characteristics. RESULT(S): Cancer patients as a
      group had significantly higher DNA damage when compared with controls. Specimens
      with high COMPalpha(t) values (percentage of sperm with denatured DNA) were
      present in all groups of cancer patients. No meaningful correlation was seen
      between the extent of DNA damage and classical semen measures. CONCLUSION(S): DNA
      damage in spermatozoa is prevalent in the majority of cancer patients. SCSA
      provides important information about the biochemical integrity of sperm DNA in
      men with cancer before their treatment.

PMID- 11239526
TI  - Absence of deleted in azoospermia (DAZ) genes in spermatozoa of infertile men
      with somatic DAZ deletions.
AB  - OBJECTIVE: To determine the presence or absence of the deleted in azoospermia
      (DAZ) gene clusters in the Y-bearing spermatozoa in semen of severely
      oligozoospermic men or in testicular biopsy samples of azoospermic men with
      somatic DAZ deletions. DESIGN: Prospective study. SETTING: Academic hospital.
      PATIENT(S): Nineteen patients attending our clinics for therapeutic
      intracytoplasmic injection of sperm. INTERVENTION(S): Peripheral blood
      lymphocytes were used to obtain somatic DNA for analysis using the polymerase
      chain reaction. Analysis of chromosomes X and Y and the detection of the DAZ gene
      clusters were carried out with the fluorescence in situ hybridization technique
      in spermatozoa remaining after intracytoplasmic sperm injection. MAIN OUTCOME
      MEASURE(S): Presence or absence of the DAZ gene clusters in matched somatic DNA
      and Y-bearing spermatozoa. RESULT(S): Seven patients appeared to have a somatic
      DAZ deletion. Three-color fluorescence in situ hybridization showed that all Y
      bearing spermatozoa examined from these men carried the same deletion.
      CONCLUSION(S): The DAZ deletions present in the seven men would all have been
      transmitted if they had fathered sons through artificial fertilization techniques
      using the sperm cells examined in this study.

PMID- 11239527
TI  - Effects of the hypo-osmotic swelling test on the outcome of intracytoplasmic
      sperm injection for patients with only nonmotile spermatozoa available for
      injection: a prospective randomized trial.
AB  - OBJECTIVE: Hypo-osmotic swelling test (HOST) has been shown to be an effective
      method for the selection of live sperm. On-going pregnancies were obtained by
      using HOST-selected sperm. The aim of this study was to evaluate the effect of
      using HOST-selected "live" sperm versus nonselected sperm on the outcome of
      intracytoplasmic sperm injection cycles when only nonmotile sperm were available
      for injection. DESIGN: Prospective randomized study. SETTING: Governmental
      tertiary care hospital. PATIENT(S): Thirty ICSI cycles with no motile sperm were
      included in this study. INTERVENTION(S): For the HOST group, potentially live
      spermatozoa detected by hypo-osmotic reaction of the tail were injected into
      oocytes. For the No-HOST group, the sperm were randomly injected into the oocytes
      without checking the viability. MAIN OUTCOME MEASURE(S): The fertilization,
      cleavage, embryo quality, pregnancy, and implantation rates were assessed for the
      two groups. RESULT(S): Among 30 cycles, 15 fall into each group. Fertilization,
      cleavage rates, and the number of good quality embryos were similar between two
      groups. CONCLUSION(S): HOST-selected live spermatozoa can be safely used for
      intracytoplasmic sperm injection to establish pregnancies. There is a tendency
      for higher pregnancy and implantation rates to result, but it does not reach
      statistical significance.

PMID- 11239528
TI  - Use of a levonorgestrel-releasing intrauterine device in the treatment of
      rectovaginal endometriosis.
AB  - OBJECTIVE: To evaluate the effectiveness of a levonorgestrel-releasing IUD as
      therapy for endometriosis of the rectovaginal septum. DESIGN: Prospective
      therapeutic non-randomized, self-controlled clinical trial analyzing changes in
      pain symptoms and size of lesions induced by the levonorgestrel-releasing IUD
      over 12 months. SETTING: Tertiary referral center for treatment of deep
      endometriosis. PATIENT(S): Eleven symptomatic patients with rectovaginal
      endometriosis. INTERVENTION(S): A levonorgestrel-releasing IUD was inserted and
      maintained for 12 months. MAIN OUTCOME MEASURE(S): Severity of dysmenorrhea,
      pelvic pain, and deep dyspareunia were assessed before insertion of the IUD and
      throughout treatment. The size of rectovaginal endometriotic lesions were
      evaluated by using transrectal and transvaginal ultrasonography. RESULT(S):
      Dysmenorrhea, pelvic pain, and deep dyspareunia greatly improved and the size of
      the endometriotic lesions was significantly reduced by treatment. CONCLUSION(S):
      Insertion of a levonorgestrel-releasing IUD alleviates pain and reduces the size
      of lesions in patients with endometriosis of the rectovaginal septum.

PMID- 11239529
TI  - Interleukin 1beta, interleukin-6, and tumor necrosis factor-alpha in
      endometriotic tissue and in endometrium.
AB  - OBJECTIVE: To compare the levels of IL-1beta, IL-6, and TNFalpha in endometriotic
      tissue and in endometrium from women with endometriosis and healthy controls.
      DESIGN: Open. SETTING: Department of Obstetrics and Gynecology at a university
      hospital. PATIENT(S): Twenty-six women with endometriosis and 22 controls
      operated on for clinical indications. INTERVENTION(S): ELISA in homogenized
      tissue samples collected during surgery. MAIN OUTCOME MEASURE(S): Levels of IL
      1beta, IL-6, and TNFalpha in tissue homogenates. RESULT(S): The three types of
      tissue differed significantly with respect to all three cytokines. Endometriotic
      tissue had significantly higher concentrations of IL-1beta than endometrium from
      both patients with endometriosis and healthy controls. Both endometriotic tissue
      and endometrium from patients had significantly higher concentrations of IL-6,
      and endometriotic tissue had significantly lower concentration of TNFalpha than
      did endometrium from controls. IL-1beta showed a cycle phase dependence that was
      significant in endometrium from patients, being higher in the secretory than in
      the follicular phase. IL-1beta was significantly higher in endometrioma than in
      lesions of other localizations. Concentrations of IL-1beta and IL-6 were
      positively correlated in endometriotic tissue and in endometrium from controls.
      No other significant correlations were found. CONCLUSION(S): This study has shown
      a significant production of IL-1beta, IL-6, and TNFalpha in endometriotic tissue
      and endometrium, with significant differences between the tissue types,
      indicating a deviating cytokine pattern in both endometriotic tissue and
      endometrium from women with endometriosis compared with that from healthy
      controls.

PMID- 11239530
TI  - Comparison of Diane 35 and Diane 35 plus finasteride in the treatment of
      hirsutism.
AB  - OBJECTIVE: To compare the clinical efficacy and safety of the combination of
      Diane 35 (2 mg of cyproterone acetate, and 35 microg of ethinyl estradiol) plus
      finasteride (5 mg), and Diane 35 alone in the treatment of hirsutism. DESIGN:
      Prospective randomized clinical study. SETTING: Outpatients in Erciyes University
      Medical School. PATIENT(S): Forty women with hirsutism were selected.
      INTERVENTION(S): For 1 year, group 1 patients (n = 20) were treated with Diane 35
      alone (2 mg of cyproterone acetate and 35 microg of ethinyl estradiol) daily on
      days 5 to 25 of the menstrual cycle and group 2 patients (n = 20) with Diane 35
      plus finasteride (5 mg daily). MAIN OUTCOME MEASURE(S): Hirsutism was graded at 6
      month intervals using the Ferriman-Gallwey method. The basal hormone levels of
      total and free testosterone (T), androstenedione, DHEAS, and sex-hormone-binding
      globulin (SHBG) were measured by radioimmunoassay before the study. Total T, free
      T, SHBG, and DHEAS were also measured at 6-month intervals for 1 year.
      Multiscreen blood chemistry and side effects were evaluated during the treatment.
      RESULT(S): Thirty-four patients completed the 12-month study period. A
      significant decrease in the hirsutism score as compared to baseline was observed
      after 12 months with both Diane 35 treatment (mean +/- SD, 15.62 +/- 4.89 vs.
      9.75 +/- 3.97) and Diane 35 plus finasteride treatment (16.27 +/- 6.90 vs. 8.38
      +/- 4.44). The percentage decreases in the hirsutism score (mean percent +/- SD)
      were 30.26 +/- 14.56 vs. 34.70 +/- 11.60 at 6 months, 38.09 +/- 11.46 vs. 48.14
      +/- 14.27 at 12 months in the Diane 35 and the Diane 35 plus finasteride groups,
      respectively. The percentage reduction in the hirsutism score in the Diane 35
      plus finasteride group at 12 months was greater than in the Diane 35 group (P
      <.05). CONCLUSION(S): The percentage decrease in the hirsutism score at 12 months
      was higher in the Diane 35 plus finasteride group than in the Diane 35 group. We
      believe that Diane 35 plus finasteride is an effective and safe combination for
      the treatment of hirsutism.

PMID- 11239531
TI  - Effects of laparoscopic ovarian drilling on adrenal steroids in polycystic ovary
      syndrome patients with and without hyperinsulinemia.
AB  - OBJECTIVE: To evaluate adrenal steroid responses to ACTH stimulation and insulin
      responses to oral glucose tolerance test (OGTT) in clomiphene-citrate-resistant
      anovulatory women with polycystic ovary syndrome (PCOS) before and after
      laparoscopic ovarian drilling. DESIGN: Prospective study. SETTING: Healthy
      participants in a university teaching hospital. PATIENT(S): Twenty clomiphene
      citrate-resistant anovulatory women with PCOS. INTERVENTION(S): Laparoscopic
      ovarian drilling. MAIN OUTCOME MEASURE(S): Adrenal steroid responses to ACTH
      stimulation and insulin responses to OGTT before and after ovarian drilling.
      RESULT(S): Fourteen of 20 women completed the study. There was a correlation
      between body mass index and basal insulin levels before ovarian drilling. This
      correlation was lost after surgery. Area-under-the-curve glucose and insulin
      values before surgery in women with hyperinsulinemia (1,033.3 +/- 112.7 mmol/L
      and 141,919 +/- 26,177 pmol/L, respectively) were significantly higher than in
      those with normoinsulinemia (777.1 +/- 77.2 mmol/L and 69,867 +/- 19,390 pmol/L
      respectively, P<.05). There was a significant difference in insulin and glucose
      responses before and after ovarian drilling in women with hyperinsulinemia. No
      difference was found in women with normoinsulinemia. There was no significant
      difference in adrenal steroid responses to ACTH stimulation before and after
      ovarian drilling. CONCLUSION(S): PCOS women with hyperinsulinemia respond
      differently to laparoscopic ovarian drilling than do those with normoinsulinemia.
      Among women with hyperinsulinemia, surgery decreases glucose and insulin
      responses to OGTT. Regardless of the insulin level, laparoscopic ovarian drilling
      does not influence adrenal steroid dynamics.

PMID- 11239532
TI  - Metformin treatment of patients with polycystic ovary syndrome undergoing in
      vitro fertilization improves outcomes and is associated with modulation of the
      insulin-like growth factors.
AB  - OBJECTIVE: To determine if metformin therapy improves in vitro fertilization
      (IVF) outcomes in patients with clomiphene-resistant polycystic ovarian syndrome
      (PCOS). DESIGN: Retrospective data analysis of selective groups of patients.
      SETTING: A private IVF unit. PATIENT(S): Forty-six women with clomiphene citrate
      resistant PCOS underwent 60 cycles of IVF embryo transfer with intracytoplasmic
      sperm injection. INTERVENTION(S): In half of the cycles, patients received
      metformin (1000 to 1500 mg) daily, starting the cycle prior to gonadotropin
      treatment. MAIN OUTCOME MEASURE(S): Total number of follicles; serum estradiol
      (E2) on the day of hCG administration and the cycle's E2 maximum; total number of
      oocytes, mature oocytes, embryos, fertilization, and pregnancy rates; and
      follicular fluid levels of insulin-like growth factors (IGF-I, IGF-II) and IGF
      binding proteins (IGFBP-1, IGFBP-3). RESULT(S): In patients treated with
      metformin, the total number of follicles on the day of hCG treatment was
      decreased (23 +/- 1.2 vs. 33 +/- 2.6) with no change in follicles > or = 14 mm in
      diameter (21 +/- 1.2 vs. 25 +/- 1.7). Metformin treatment did not affect the mean
      number of oocytes retrieved (22 +/- 1.9 vs. 20.3 +/- 1.5). However, the mean
      number of mature oocytes (18.4 +/- 1.5 vs. 13 +/- 1.5) and embryos cleaved (12.5
      +/- 1.5 vs. 5.9 +/- 0.9) were increased after metformin treatment. Fertilization
      rates (64% vs. 43%) and clinical pregnancy rates (70% vs.30%) were also
      increased. Metformin led to modulation of preovulatory of follicular fluid IGF
      levels with increases of IGF-I (140 +/- 8 vs. 109 +/- 7ng/mL) and decreased of
      IGFBP-1 (133 +/- 8 vs.153 +/- 9ng/mL). CONCLUSION(S): Metformin use appears to
      improve IVF outcomes in patients with clomiphene citrate-resistant PCOS.

PMID- 11239533
TI  - A two- versus three-embryo transfer: the oocyte donation model.
AB  - OBJECTIVE: To compare implantation and pregnancy rates in oocyte recipients
      undergoing a two-embryo versus three-embryo transfer, 3 days after retrieval.
      DESIGN: Retrospective comparative analysis. SETTING: University-based in vitro
      fertilization center. PATIENT(S): All oocyte recipients undergoing embryo
      transfer from January 1, 1997 through August 31, 1999. INTERVENTION(S):
      Recipients received two or three embryos. MAIN OUTCOME MEASURE(S): Implantation,
      and clinical and multiple pregnancy rates. RESULT(S): Seventy-three recipients
      underwent a two-embryo transfer, and 376 had three embryos replaced. The numbers
      of oocytes retrieved (12.7 +/- 0.89 vs. 13.1 +/- 0.36) and embryos obtained (8.05
      +/- 0.65 vs. 8.77 +/- 0.27) did not differ between the two-embryo and three
      embryo transfer groups, nor did the proportion of patients with embryo
      cryopreservation (54.3% vs. 42.6%, respectively). There was no significant
      difference in pregnancy or implantation rates when comparing those patients with
      a two-embryo transfer to those with a three-embryo transfer. Significantly, 13.8%
      of the pregnancies in the three-embryo transfer group were triplet.
      CONCLUSION(S): Reducing the number of embryos transferred in an oocyte donation
      cycle can lower the incidence of triplet pregnancies without significantly
      lowering the overall pregnancy rate.

PMID- 11239534
TI  - Blastocyst-stage transfer of poor-quality cleavage-stage embryos results in
      higher implantation rates.
AB  - OBJECTIVE: To determine the feasibility and success of blastocyst-stage embryo
      transfers in patients having only fair and poor quality cleavage-stage embryos on
      day 3. DESIGN: Prospective case study with historic controls. SETTING: Tertiary
      care private hospital IVF center. PATIENT(S): A total of 158 day 5 embryo
      transfer cycles in patients with grade 3 and grade 4 cleavage-stage embryos.
      Control group consisted of 162 day 3 transfer cycles performed with embryos of
      similar quality. INTERVENTION(S): In vitro culture of embryos up to the
      blastocyst stage. MAIN OUTCOME MEASURE(S): The percentage of cycles that
      culminated in the transfer of at least one blastocyst and implantation and
      pregnancy rate related to the day of transfer. RESULT(S): In the day 3 transfer
      group, a mean of 5.2 embryos were replaced per patient. This was significantly
      more than the mean of 2.4 embryos that could be replaced on day 5 (P <.001). The
      clinical pregnancy rate per embryo transfer was 27.2% and 33.5% in the two
      groups, respectively (P >.05). The implantation rate per embryo was significantly
      higher in the day 5 transfer group (15% vs. 5.9%). The multiple pregnancy and
      abortion rates were similar between the groups. CONCLUSION(S): Transfer of fair
      and poor quality embryos at the blastocyst stage is feasible and is associated
      with higher implantation rates as compared to transfer of similar quality embryos
      on day 3.

PMID- 11239535
TI  - Role of periovulatory luteinizing hormone concentrations during assisted
      reproductive technology cycles stimulated exclusively with recombinant follicle
      stimulating hormone.
AB  - OBJECTIVE: To study the effect of endogenous luteinizing hormone (LH)
      concentration on fertilization, pregnancy, and early pregnancy loss rates.
      DESIGN: Retrospective cohort study. SETTING: Tertiary-care university center.
      PATIENT(S): One hundred sixty-six normogonadotropic patients undergoing IVF.
      INTERVENTION(S): Luteal phase pituitary down-regulation and recombinant FSH
      (Gonal-F) were used for ovarian stimulation. The mean of 4-5 serum LH
      concentrations, from stimulation days 5-12, was computed for analysis. MAIN
      OUTCOME MEASURE(S): Fertilization, pregnancy, and early pregnancy loss rates
      according to periovulatory levels of LH. RESULT(S): Data were analyzed by
      stratifying patients according to a mean periovulatory LH value of 3 mIU/mL.
      After controlling for confounding variables with logistic regression, results
      showed that the fertilization rate was significantly lower in patients with a
      periovulatory LH <3 mIU/mL versus > or = 3 mIU/mL (52% and 58%, respectively;
      P=.03). Pregnancy rates and spontaneous abortion rates were similar in both
      groups. There were seven biochemical pregnancies, all in patients with an LH <3
      mIU/mL (P=.07). CONCLUSION(S): Low endogenous LH concentrations (<3 mIU/mL) in
      the late follicular phase of an IVF cycle are associated with significantly lower
      fertilization rates and a trend toward higher biochemical pregnancy rates. It may
      be of clinical benefit, when exclusively using r-hFSH in ART cycles, to add LH in
      the late follicular phase or to further reduce the dose of GnRH agonist.

PMID- 11239536
TI  - Embryo score is a better predictor of pregnancy than the number of transferred
      embryos or female age.
AB  - OBJECTIVE: To compare the value of 17 IVF variables, including a new mean score
      of transferred embryos (MSTE), in predicting pregnancy rate. DESIGN:
      Retrospective study. SETTING: Private IVF unit. PATIENT(S): Women who underwent
      10,000 embryo transfers. MAIN OUTCOME MEASURE(S): Duration of infertility, type
      of infertility, female age, rank of IVF attempt, type of ovarian treatment,
      progesterone level, sperm count, sperm motility, sperm morphology, number of
      retrieved oocytes, number of mature oocytes, maturation rate, number of embryos
      obtained, fertilization rate, number of transferred embryos, cumulative embryo
      score (CES), mean score of transferred embryos (MSTE), and pregnancy rate.
      RESULT(S): Outcome of IVF-ET was significantly correlated with female age, type
      of infertility, number of retrieved oocytes, number of mature oocytes, maturation
      rate, embryos obtained, fertilization rate, transferred embryos, CES, and MSTE.
      Multivariate analysis demonstrated that MSTE was a better predictor of pregnancy
      than the number of transferred embryos and female age. CONCLUSION(S): Embryo
      quality is the best predictor of pregnancy. The embryo score described herein
      should be used in IVF-ET programs to choose the best embryos for transfer.

PMID- 11239537
TI  - Membrane permeability of human oocytes in the presence of the cryoprotectant
      propane-1,2-diol.
AB  - OBJECTIVE: To determine the permeability of unfertilized human oocytes to water
      and the cryoprotectant propane-1,2-diol over a range of temperatures and to use
      these data to predict osmotic responses under given conditions. DESIGN:
      Laboratory-based study. SETTING: Teaching hospital. PATIENT(S): Infertility
      patients donating unfertilized oocytes in excess of those required for treatment.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Water and cryoprotectant
      permeability were determined from measurements of oocyte volume excursions on
      exposure to 1.5 M propane-1,2-diol at 30 degrees C, 24 degrees C, and 10 degrees
      C. RESULT(S): Permeability of human oocytes to water and cryoprotectant increased
      as temperature increased. The predicted response of oocytes, based on these data,
      closely matched the measured response of an oocyte on exposure to a widely used
      method for addition of cryoprotectant before freezing. CONCLUSION(S): Commonly
      used cryopreservation protocols involving slow cooling in the presence of propane
      1,2-diol cause potentially damaging excursions in cell volume on exposure to
      cryoprotectant. Modifications that can be expected to reduce cell volume
      excursions, based on oocyte permeability data, are suggested.

PMID- 11239538
TI  - Value of the serum estradiol level on the day of human chorionic gonadotropin
      injection and on the day after in predicting the outcome in natural in vitro
      fertilization/intracytoplasmic sperm injection cycles.
AB  - OBJECTIVE: To predict the risk of premature ovulation and possibility of
      pregnancy in natural IVF/ICSI cycles on the basis of the estradiol (E2) level on
      the day of hCG injection and on the day after. DESIGN: A prospective study.
      SETTING: Hospital research program. PATIENT(S): One hundred sixty-four women
      undergoing 305 IVF/ICSI natural cycles. INTERVENTION(S): Serum E2 levels were
      measured approximately 12 h before (day 0) and 12-17 h after hCG administration
      (day 1). MAIN OUTCOME MEASURE(S): E2 levels on day 0 and day 1, the ratio of the
      day 1 to day 0 levels, and cycle outcome. RESULT(S): In cycles with premature
      ovulation and in conception cycles, the average E2 level on day 0 was
      statistically significantly higher than in other cycles, whereas the E2 ratio was
      statistically significantly lower. Multiple logistic regression was used to
      determine the connection of the E2 level on day 0 (B0 = -0.742, B = 2.147, P
      =.01) and the E2 ratio (B0 = -0.742, B = -3.135, P<.001) with premature
      ovulation. Only the E2 ratio (B0 = 0.659, B = -2.209, P =.0068) was significantly
      connected with conception. CONCLUSION(S): In predicting the outcome of natural
      IVF/ICSI cycles, the importance lies not in the E2 level on the day of hCG
      administration or on the day after, but rather in the E2 ratio.

PMID- 11239539
TI  - Psychological correlates of vasectomy.
AB  - OBJECTIVE: To examine the thoughts and concerns of men contemplating vasectomy
      before speaking to a physician as well as their partner's role in reaching this
      decision. DESIGN: A questionnaire analysis using response rates, ANOVA, and
      regression analyses. SETTING: A large Midwestern teaching hospital. PATIENT(S):
      Visitors to the urology clinic of the hospital. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): [1] Questionnaire designed by authors. [2] Measures of self
      concept, relationship satisfaction, and problem-solving abilities. RESULT(S): [1]
      Subjects had been considering vasectomy for an average of 1 year and were fairly
      certain of their decision. [2] Anxiety about vasectomy surgery was mostly driven
      by fear about pain and fear of the unknown. [3] Concerns about the finality of
      the procedure did not emerge as a big concern. [4] There is confusion about the
      reversibility of the procedure. [5] Subjects are better problem solvers and have
      a higher self-concept than people in general. CONCLUSION(S): Our findings
      demonstrate the need for adequate prevasectomy counseling, particularly in the
      area of postoperative expectations, as well as reversibility of the procedure.

PMID- 11239540
TI  - Differences in hormonal characteristics of conceptive versus nonconceptive
      menstrual cycles.
AB  - OBJECTIVE: To determine the hormonal characteristics of a fecund menstrual cycle.
      DESIGN: Prospective observational study. SETTING: Clinical research center.
      PATIENT(S): Fourteen patients having artificial insemination with donor semen
      provided daily blood and urine samples in a nonconceptive cycle and the
      consecutive conceptive cycle. INTERVENTION(S): Concentrations of E2, luteinizing
      hormone, follicle-stimulating hormone (FSH), and P4 were measured in serum. Urine
      samples were analyzed for metabolites of E2, P4, and FSH. MAIN OUTCOME
      MEASURE(S): The serum and urinary hormone profiles of the periovulatory period
      were compared in conceptive and nonconceptive cycles. RESULT(S): The mean peak
      value of periovulatory urinary FSH was significantly higher in conceptive cycles
      than in nonconceptive cycles. The mean serum E2 concentration was significantly
      higher on day 0 (day of peak urinary FSH concentration) in conceptive cycles than
      in nonconceptive cycles, but mean peak values of serum E2 did not differ
      significantly. No other significant differences were observed in serum and
      urinary hormone profiles between conceptive and nonconceptive cycles.
      CONCLUSION(S): A lower, broader peak of FSH in urine was observed in
      nonconceptive cycles compared with conceptive cycles. Urinary FSH measurements
      may be useful in predicting less fecund ovulatory cycles and may identify some
      types of reduced female fertility.

PMID- 11239541
TI  - Differential effects on the androgen status of postmenopausal women treated with
      tibolone and continuous combined estradiol and norethindrone acetate replacement
      therapy.
AB  - OBJECTIVE: To determine serum parameters reflective of androgen status in
      postmenopausal women using two types of hormone replacement therapy (HRT).
      DESIGN: Randomized, double-blind, prospective 1-year trial of two oral HRT
      regimens. SETTING: University hospital, department of obstetrics and gynecology,
      menopause clinic. PATIENT(S): 100 postmenopausal women > or = 45 years.
      INTERVENTION(S): Daily use of the progestogen tibolone (2.5 mg; n = 50) or
      continuous combined 17-beta-estradiol (2 mg) and norethindrone acetate (E+NA, 1
      mg; n = 50). MAIN OUTCOME MEASURE(S): Measurements of total testosterone (total
      T), dehydroepiandrosterone sulfate (DHEAS), androstenedione (A), FSH, and sex
      hormone-binding globulin (SHBG), and calculations of free testosterone (free T).
      Assessment of changes from baseline within and between groups after 6 and 12
      months. RESULT(S): We found significant differences (% changes) in the tibolone
      group compared to baseline within the groups after both 6 and 12 months,
      respectively. Levels of free T doubled, total T decreased slightly, and SHBG
      decreased by half; DHEAS increased by approximately 20%; and FSH decreased. In
      the E+NA group, levels of free T, total T, androstenedione, and FSH all
      decreased, and SHBG increased. Pre-trial levels of DHEAS, A, and total T were
      significantly higher in the E+NA group. Between groups throughout the study, the
      changes from baseline were significant due to the different extent of FSH
      reduction, and opposite changes of free T, SHBG, and DHEAS. CONCLUSION(S): Both
      regimens modify plasma androgens, DHEAS, and SHBG differently. Tibolone decreased
      the levels of SHBG, and substantially increased free T and to a lesser extent
      increased DHEAS; this may reflect a modification of adrenal androgen production.
      Continuous combined estradiol and norethindrone acetate HRT suppressed the
      peripheral plasma androgens mediated by increased levels of SHBG.

PMID- 11239542
TI  - Survival analysis of fertility after ectopic pregnancy.
AB  - OBJECTIVE: To evaluate the reproductive outcome after ectopic pregnancy and to
      assess the contribution of risk factors to future fertility. DESIGN: Prospective
      follow-up in a population-based sample. SETTING: Register of ectopic pregnancies
      established in an urban area around Lille, France. PATIENT(S): Three hundred and
      twenty-eight women treated between April 1994 and March 1997 who had not been
      using an IUCD at the time of the ectopic pregnancy and were trying to become
      pregnant. INTERVENTION(S): Interviews by telephone every 6 months for 2 years and
      once yearly thereafter. MAIN OUTCOME MEASURE(S): Cumulative pregnancy rate.
      RESULT(S): Two hundred fifteen (65.5%) women became pregnant after a mean of 5
      months. One hundred eighty-two (84.7%) pregnancies were intrauterine; 22 (10.2%)
      were recurrent ectopic pregnancies; and in 11 women (5.1%), it was too early to
      define implantation. The cumulative intrauterine pregnancy rate was 56% at 1 year
      and 67% at 2 years. After applying Cox regression, three factors associated with
      fertility seemed to decrease reproductive performance: age > 35 years, history of
      infertility, and anterior tubal damage . CONCLUSION(S): More than half of the
      women treated for ectopic pregnancy spontaneously conceived and had a normally
      progressive pregnancy at 1 year. Fertility depends more on established patient
      characteristics than characteristics of ectopic pregnancy itself or treatment
      thereof.

PMID- 11239543
TI  - Genotype distribution of estrogen receptor-alpha gene polymorphisms in Italian
      women with surgical uterine leiomyomas.
AB  - OBJECTIVE: To explore a possible association between estrogen receptor-alpha (ER
      alpha) gene polymorphisms and development of uterine leiomyomas. DESIGN: Case
      control study. SETTING: University teaching hospital. PATIENT(S): 119 women with
      clinically and surgically diagnosed uterine leiomyomas. INTERVENTION(S):
      Therapeutic hysterectomy. MAIN OUTCOME MEASURE(S): Frequency and distribution of
      ER-alpha gene polymorphisms. RESULT(S): No statistically significant differences
      between controls and patients in the allele frequency and genotype distribution
      were found when Pvu II and Xba I restriction polymorphism sites were analyzed
      separately. When the two ER-alpha gene polymorphisms were analyzed in
      combination, five major genotypes were recognized in controls or patients; the
      frequency differed slightly but not significantly between groups. CONCLUSION(S):
      The Pvu II and Xba I polymorphisms in the ER-alpha gene do not produce different
      risks of developing uterine leiomyomas.

PMID- 11239544
TI  - Cost-effectiveness of hysterosalpingography, laparoscopy, and Chlamydia antibody
      testing in subfertile couples.
AB  - OBJECTIVE: To evaluate the cost-effectiveness analysis of hysterosalpingography
      (HSG), laparoscopy, and Chlamydia antibody testing (CAT) in subfertile couples.
      DESIGN: Cost-effectiveness analysis. SETTING: Decision analytic framework.
      PATIENT(S): Data of >2,000 subfertile couples in the Canadian Infertility
      Treatment Evaluation Study. Results of CA-125 measurement and CAT were simulated
      from baseline characteristics. INTERVENTION(S): Expectant management was
      considered to be the reference strategy (strategy 1). In strategy 2 and 3, IVF
      was offered either immediately or after 2.5 years. In strategy 4, the decision to
      offer or delay treatment was based on the couple's chance of spontaneous
      conception. Nine strategies incorporated combinations of CAT, CA-125 measurement,
      HSG, and laparoscopy. MAIN OUTCOME MEASURE(S): Expected live birth rates,
      expected number of IVF cycles, and expected total costs. RESULT(S): The strategy
      starting with CAT was the most cost-effective in couples whose 3-year chance of
      conception was >14%, whereas the strategy starting with HSG was the most cost
      effective in couples with worse fertility prospects. CONCLUSION(S): The
      diagnostic work-up to detect tubal pathology in subfertile couples should start
      with CAT in couples with relatively good fertility prospects and immediate HSG in
      couples with relatively poor fertility prospects.

PMID- 11239545
TI  - Decreased suppression of antibody-dependent cellular cytotoxicity by seminal
      plasma in unexplained infertility.
AB  - OBJECTIVE: To determine whether seminal plasma (SP) from unexplained infertile
      males has different suppressive activity on antibody-dependent cellular
      cytotoxicity (ADCC) than SP from fertile males or SP from males of couples with
      known infertility factor. DESIGN: Comparative clinical/experimental study.
      SETTING: In vitro fertilization program in a university hospital and a hospital
      research laboratory. PATIENT(S): A total of 245 SP samples from 174 infertile and
      16 fertile couples were compared. INTERVENTION(S): SP suppression of ADCC was
      measured by using human 51chromium-labeled red blood cells (RBC), sensitized with
      IgG-rabbit-anti-human-RBC as targets and peripheral blood lymphocytes as effector
      cells. MAIN OUTCOME MEASURE(S): Suppressive activity of each sample was
      determined by calculating 51Cr-release in the presence and absence of SP.
      RESULT(S): When analyzed with respect to sperm number, motility, and morphology,
      suppressive activities of samples with normal semen analyses (n = 142) were
      significantly higher (x = 37% +/- 14%) than suppressive activities of abnormal
      samples (n = 103; x = 32% +/- 13%). There was no strong correlation of
      suppressive activity to other semen parameters. Within the andrologically normal
      males, SP from the unexplained infertile couples (n = 15) showed significantly
      lower suppressive activity (x = 24% +/- 11%) compared with the SP from fertile
      males (n = 16; x = 35% +/- 13%) and from couples with female infertility factor
      (n = 65; x = 39% +/- 14%). CONCLUSION(S): Loss of suppressive activity is
      associated with unexplained infertility, even in male patients who previously
      were considered normal by traditional methods of semen analysis.

PMID- 11239546
TI  - Fluorescent probes allow rapid and precise recording of follicle density and
      staging in human ovarian cortical biopsy samples.
AB  - OBJECTIVE: To develop rapid and reliable techniques for determining follicle
      content, viability, and morphologic features in an ovarian cortical biopsy
      specimen. DESIGN: Prospective laboratory study. SETTING: Academic research
      institution. PATIENT(S): Consenting patients undergoing laparoscopic surgery for
      nonovarian disease. INTERVENTION(S): Ovarian cortical biopsy specimens were
      stained by using fluorescent probes and conventional histologic stains.
      Observations were made by using light, fluorescent, and confocal laser
      microscopy. MAIN OUTCOME MEASURE(S): Density, cellular viability, and morphologic
      features of ovarian follicles. RESULT(S): After 45 minutes of incubation of
      ovarian cortical tissue with calcein AM, follicles were visualized by fluorescent
      microscopy and counted. Ten minutes of exposure is sufficient to stain all cell
      nuclei with the PicoGreen probe. Subsequent confocal microscopy allows
      quantification of follicle density and reveals follicle morphology in the optical
      sections. Follicle density as assessed by using these rapid methods was
      concordant with the number of units counted in conventionally stained histologic
      sections. CONCLUSION(S): Use of fluoroprobes for mitochondrial and DNA staining
      allows rapid evaluation of follicle density in ovarian tissue.

PMID- 11239547
TI  - Role of laparoscopic salpingostomy in the treatment of hydrosalpinx.
AB  - OBJECTIVE: To determine pregnancy rates after laparoscopic salpingostomy in
      occlusive distal tubal disease. To evaluate the relative impact of various
      historical, physical, and operative factors on pregnancy outcome using a
      multivariate statistical analysis. DESIGN: Prospective cohort. SETTING:
      University-affiliated tertiary care infertility clinic. PATIENT(S): One hundred
      thirty-nine infertile women with occlusive distal tube disease. INTERVENTION(S):
      Laparoscopic salpingostomy. MAIN OUTCOME MEASURE(S): The occurrence of
      intrauterine (IUP) and ectopic pregnancy (EP). RESULT(S): The overall IUP and EP
      rates were 24.5% and 16.5%, respectively. Analysis of historical variables,
      assessed independently, demonstrated a significantly higher IUP rate with a
      positive history of gonorrhea and a significantly higher EP rate with a positive
      history of pelvic inflammatory disease, lack of history of intrauterine device
      (IUD) usage, or the performance of a bilateral procedure. The logistic regression
      model to predict intrauterine pregnancy had an overall predictive value of 77.5%
      and included the following significant variables: secondary infertility, positive
      history of gonorrhea, and the operative finding of moderate periadnexal
      adhesions. The logistic regression model to predict ectopic pregnancy had an
      overall predictive value of 89.0% and included the following significant
      variables: previous ectopic pregnancy, negative history of IUD use, positive
      history of PID, a bilateral procedure, and perihepatic adhesions. CONCLUSION(S):
      Operative laparoscopy may be effective for the correction of hydrosalpinges in
      selected patients. The probability of achieving an intrauterine or an ectopic
      pregnancy can be predicted based on combinations of significant variables.

PMID- 11239548
TI  - Pressure lavage under ultrasound guidance: a new approach for outpatient
      treatment of intrauterine adhesions.
AB  - OBJECTIVE: To present pressure lavage under ultrasound guidance (PLUG) as a new
      therapeutic procedure for selected cases of intrauterine adhesions (IUA). DESIGN:
      An open clinical investigation with no control group. SETTING: Teaching hospital.
      PATIENT(S): Seven consecutive patients referred to our department for secondary
      amenorrhea due to IUA. INTERVENTION(S): A newly developed technique based on
      sonohysterography was used to monitor the effects of intrauterine injections of
      saline solution on the continuous accumulation of saline in the uterine cavity
      for the mechanical disruption of IUA. MAIN OUTCOME MEASURE(S): Lysis of
      intrauterine adhesions, restoration of menses, and increased pregnancy rate in
      infertile patients. RESULT(S): Five patients with mild IUA obtained satisfactory
      lysis of adhesions by the use of the PLUG technique. A second-look hysteroscopy
      after 1 month showed that filmy adhesions persisted in two patients with moderate
      IUA. These adhesions were removed successfully during hysteroscopy. Restoration
      of menses was obtained and has continued in all patients. Two of the three
      infertile patients became pregnant. CONCLUSION(S): This technique is safe and
      ideal as an in-office procedure. PLUG allows complete lysis in mild IUA cases,
      and the need for therapeutic, and possibly follow-up hysteroscopy, can be
      avoided. In moderate IUA cases, the procedure may represent a useful initial step
      in reducing the need for operative hysteroscopy.

PMID- 11239549
TI  - Operative transvaginal hydrolaparoscopy for treatment of polycystic ovary
      syndrome: a new minimally invasive surgery.
AB  - OBJECTIVE: To evaluate a new minimally invasive surgery for treatment of the
      polycystic ovary syndrome (PCOS) in clomiphene-resistant infertile women. DESIGN:
      Prospective study. SETTING: University teaching hospital. PATIENT(S): Thirteen
      clomiphene citrate-resistant anovulatory women with PCOS. INTERVENTION(S):
      Operative transvaginal hydrolaparoscopy (THL) using a coaxial bipolar electrode.
      MAIN OUTCOME MEASURE(S): Feasability, ovulation rate, and pregnancy rate.
      RESULT(S): Ovarian drilling was performed by THL in all patients; no surgical
      complications occurred. Mean (+/-SD) duration of follow-up time was 6.3 +/- 3.3
      months. Six patients recovered to have regular ovulatory cycles. Six pregnancies
      occurred; three were spontaneous, two occurred after stimulation and intrauterine
      insemination, and one occurred after IVF. The cumulative pregnancy rate was 33%
      at 3 months after THL and 71% at 6 months after THL. No miscarriages occurred.
      CONCLUSION(S): Transvaginal hydrolaparoscopy with ovarian drilling using bipolar
      electrosurgery appears to be an alternative minimally invasive in patients with
      PCOS who are resistant to clomiphene therapy.

PMID- 11239550
TI  - Laparoscopic management of hydrosalpinges before in vitro fertilization-embryo
      transfer: salpingectomy versus proximal tubal occlusion.
AB  - OBJECTIVE: To compare ovarian response and IVF-ET cycle outcome in patients with
      hydrosalpinges managed by either laparoscopic salpingectomy or proximal tubal
      occlusion. DESIGN: Retrospective analysis. SETTING: Tertiary-care assisted
      reproductive technology program. PATIENT(S): One hundred four consecutive fresh
      IVF-ET cycles in 94 patients with tubal-factor infertility. INTERVENTION(S):
      Laparoscopic salpingectomy (group 1: 35 cycles) or bipolar proximal tubal
      occlusion (group 2: 17 cycles), controlled ovarian hyperstimulation, and IVF-ET.
      Control groups consisted of both tubal-factor patients without hydrosalpinges
      (group 3: 37 cycles) and those with prior bilateral tubal ligation for
      sterilization (group 4: 15 cycles). MAIN OUTCOME MEASURE(S): Uterine artery
      Doppler flow, controlled ovarian hyperstimulation response, and implantation and
      clinical pregnancy rates. RESULT(S): There were no differences in mean uterine
      artery pulsatility indices or ovarian response among any of the groups. A trend
      toward a higher cycle cancellation rate in group 1 did not approach statistical
      significance. Clinical pregnancy and implantation rates were not significantly
      different between group 1 (57.1%, 29.2 +/- 5.9%, respectively) and group 2
      (46.7%, 19.4 +/- 6.1%, respectively) or compared with those of controls.
      CONCLUSION(S): [1] Management of hydrosalpinges by laparoscopic salpingectomy or
      bipolar proximal tubal occlusion yielded statistically similar responses to
      controlled ovarian hyperstimulation and IVF-ET cycle outcome. [2] The latter
      approach may be preferable in patients who present with dense pelvic adhesions
      and easy access only to the proximal fallopian tube.

PMID- 11239551
TI  - Multiple globules in a cystic ovarian teratoma.
AB  - OBJECTIVE: To describe the characteristic imaging findings of multiple globules
      and globules-fluid level in a cystic ovarian teratoma. DESIGN: Descriptive case
      study. SETTING: Mackay Memorial Hospital and National Yang-Ming University,
      Taipei, Taiwan, Republic of China. PATIENT(S): A 20-year-old woman with left
      abdominal discomfort and a palpable mass on the left side of the distended
      abdomen. INTERVENTION(S): Surgical removal of a 10-cm cystic ovarian teratoma
      that contained chocolate-like fluid and multiple spheroid mobile globules
      consisting of yellowish sebaceous debris and fine hair shafts. MAIN OUTCOME
      MEASURE(S): Plain abdominal radiography, ultrasonography, and computed tomography
      (CT). RESULT(S): Plain abdominal radiography revealed no calcification in the
      mass. The first sonographic examination showed no movement by positional change
      of multiple rounded echogenic masses ranging from 0.5 cm to 2 cm in diameter, but
      the second CT examination done after the patient had spent some time lying down
      showed that the rounded masses arrayed in the upper portion of the cyst and
      displayed the characteristic level of globules-fluid. Thus, the differential
      diagnosis was multiple mobile globules in a cystic ovarian tumor. CONCLUSION(S):
      This case indicates that fatty masses need time to float upward in the fluid
      matrix of a cystic ovarian teratoma. This delayed effect should be considered
      when an ovarian cyst with multiple rounded echogenic masses is diagnosed by
      ultrasonography, CT, or magnetic resonance imaging.

PMID- 11239552
TI  - Goserelin acetate (Zoladex) plus endometrial ablation for dysfunctional uterine
      bleeding: a 3-year follow-up evaluation.
AB  - OBJECTIVE: To report the results of a 3-year follow-up evaluation of a trial
      comparing goserelin acetate depot injections with sham injections before
      endometrial ablation for the treatment of dysfunctional uterine bleeding (DUB).
      DESIGN: Prospective, randomized, double-blind, parallel-group study. SETTING:
      Thirty-seven centers in 12 countries. PATIENT(S): Three-hundred and fifty-eight
      premenopausal women aged over 30 years with DUB. INTERVENTION(S): Goserelin
      acetate (3.6 mg depot) every 28 days for 8 weeks, or sham depot every 28 days for
      8 weeks, with endometrial ablation 6 weeks +/- 3 days after the first depot
      injection (i.e., when the endometrium is at its thinnest). The follow-up
      continued for 3 years. MAIN OUTCOME MEASURE(S): At the 3-year follow-up, bleeding
      in the previous 3 months and need for surgical intervention were recorded.
      RESULT(S): At 3 years, amenorrhea rates were 21% in the goserelin acetate group
      and 14% in the control group (estimated odds ratio, 1.8; 95% CI, 0.98-3.25;
      P=.0571). The surgical intervention rate (since the original procedure) was low
      and did not differ significantly between groups. For hysterectomy, it was 21% for
      the goserelin acetate group and 15% for the control group. For repeat ablations,
      it was 5.6% for the goserelin acetate group and 2.1% for the control group.
      CONCLUSION(S): Prethinning with goserelin acetate before endometrial ablation
      resulted in higher long-term amenorrhea rates than ablation without prethinning.

PMID- 11239553
TI  - Spontaneous conception in the presence of stage IIIC endometrioid ovarian cancer.
AB  - OBJECTIVE: To describe a rare case of spontaneous conception in a patient with a
      preexisting metastatic ovarian cancer. DESIGN: Case report. SETTING: University
      hospital. PATIENT(S): A 39-year-old Asian woman who conceived while undergoing an
      evaluation for primary infertility and newly detected bilateral adnexal masses.
      INTERVENTION(S): Staging laparotomy and total abdominal hysterectomy and
      bilateral salpingo-oophorectomy. MAIN OUTCOME MEASURE(S): Anatomic pathology
      diagnosis. RESULT(S): Blighted ovum and stage IIIC endometrioid adenocarcinoma of
      ovary. CONCLUSION(S): Metastatic ovarian cancer does not prevent either
      spontaneous ovulation or spontaneous conception.

PMID- 11239555
TI  - Pregnancies achieved after transferring frozen morula/compact stage embryos.
AB  - OBJECTIVE: To report two cases of frozen embryo transfers in which embryos were
      frozen at the morula/compact stage and pregnancies were achieved after transfer.
      DESIGN: Case report. SETTING: Private assisted reproductive program. PATIENT(S):
      Two women had transfer of embryos that were frozen at the morula/compact stage.
      INTERVENTION(S): Human morula/compact embryos were cryopreserved and transferred
      after subsequent thaw. MAIN OUTCOME MEASURE(S): Embryo survival after thawing and
      subsequent pregnancy outcome. RESULT(S): Three and five compact embryos were
      frozen on day 4 for two patients, respectively. In the first case, all three
      embryos survived after thawing, and all were transferred. In the second patient,
      three of five embryos survived after thawing, and those three surviving embryos
      were transferred. Pregnancies were achieved in both patients. The first woman
      became pregnant with twins and delivered two girls weighing 2,270 g and 2,071 g,
      respectively. The second patient became pregnant with a singleton and delivered a
      boy weighing 2,837 g. CONCLUSION(S): Human embryos can be frozen and thawed in
      the morula/compact stage and achieve normal pregnancy. Advantages of embryo
      freezing/thawing at the morula/compact stage include the following: [1] compared
      with earlier embryonic stage freezing, morula/compact-stage embryos provide
      better embryo selection and [2] it is easier and safer to perform assisted
      hatching on compact-stage embryos when compared with those from other
      preimplantation stages.

PMID- 11239554
TI  - Altered autophosphorylation of the insulin receptor in the ovary of a woman with
      polycystic ovary syndrome.
AB  - OBJECTIVE: To determine whether the tyrosine autophosphorylation of the insulin
      receptor (IR) in the ovary of a woman with polycystic ovary syndrome (PCOS) was
      reduced compared to normal. DESIGN: Experimental study. SETTING: Tertiary care
      medical center. PATIENT(S): One woman with PCOS and one healthy control, both of
      whom underwent a hysterectomy and bilateral salpingo-oophorectomy.
      INTERVENTION(S): Plasma membrane fraction of ovarian tissue was isolated, and the
      IR was purified and concentrated. MAIN OUTCOME MEASURE(S): Western blots of the
      IR, which had been incubated with and without insulin, were prepared.
      Colorimetric and chemiluminescent methods were used to detect the presence of the
      IR beta-subunit and IR tyrosine autophosphorylation, respectively. RESULT(S): The
      presence of the beta-subunit of the IR was identified in both ovarian samples.
      The degree of insulin-stimulated IR tyrosine autophosphorylation, reflected by
      the mean (+/-SD) relative optical density of the 95 kd band, was 4.3-fold higher
      in the normal ovary compared to the PCOS ovary (0.56 +/- 0.18 optical density vs.
      0.13 +/- 0.10 optical density, respectively). CONCLUSION(S): Tyrosine
      autophosphorylation of the IR may be decreased in the ovaries of women with PCOS,
      similar to the findings in other tissues. The mechanisms through which insulin
      acts to produce an excess in ovarian androgen production in the face of a
      decrease in ovarian IR autophosphorylation remain to be determined.

PMID- 11239556
TI  - Administration of somatostatin analogue reduces uterine and myoma volume in women
      with uterine leiomyomata.

PMID- 11239557
TI  - In vitro fertilization cycles converted to intrauterine insemination because of
      poor follicular response have low success rates.

PMID- 11239558
TI  - Impact of intracytoplasmic sperm injection on embryo cryopreservation and
      clinical outcome.

PMID- 11239559
TI  - Relationship between gonadotropin-releasing hormone agonist and myoma cellular
      activity: preliminary findings on positron emission tomography.

PMID- 11239560
TI  - Successful treatment of embryo implantation failure in patients with the Sjogren
      syndrome with low-dose prednisolone.

PMID- 11239561
TI  - Gene therapy to the rescue in Parkinson's disease.

PMID- 11239562
TI  - Gene therapy to the rescue in Parkinson's disease. Response from Kordower and
      Aebischer.

PMID- 11239563
TI  - Vasopeptidase inhibitors: an emerging class of cardiovascular drugs.

PMID- 11239564
TI  - To kill two birds with one stone: a general concept in gene regulation?

PMID- 11239565
TI  - Cannabis: a pot of cellular actions in the mesolimbic system.

PMID- 11239566
TI  - P2Y(12) - the hare catches up with the tortoise!

PMID- 11239569
TI  - Carnosine as a modulator of endogenous Zn(2+) effects.

PMID- 11239574
TI  - Molecular determinants of metabotropic glutamate receptor signaling.
AB  - Metabotropic glutamate (mglu) receptors are implicated in the regulation of many
      physiological and pathological processes in the CNS, including synaptic
      plasticity, learning and memory, motor coordination, pain transmission and
      neurodegeneration. Several recent studies have elucidated the molecular
      determinants of mglu receptor signaling and show that several mechanisms acting
      at different steps in signal propagation are involved. We attempt to offer an
      integrated view on how homologous and heterologous mechanisms regulate the
      initial steps of signal propagation, mainly at the level of mglu-receptor-G
      protein coupling. Particular emphasis is placed on the role of phosphorylation
      mechanisms mediated by protein kinase C and G-protein-coupled receptor kinases,
      and on the emerging importance of some members of the regulators of G-protein
      signaling family, such as RGS2 and RGS4, which facilitate the GTPase activity
      that is intrinsic to the alpha-subunits of G(q) and G(i).

PMID- 11239575
TI  - Structure and function of GABA(C) receptors: a comparison of native versus
      recombinant receptors.
AB  - In less than a decade our knowledge of the GABA(C) receptor, a new type of Cl(-)
      permeable ionotropic GABA receptor, has greatly increased based on studies of
      both native and recombinant receptors. Careful comparison of properties of native
      and recombinant receptors has provided compelling evidence that GABA receptor rho
      subunits are the major molecular components of GABA(C) receptors. Three distinct
      rho-subunits from various species have been cloned and the pattern of their
      expression in the retina, as well as in various brain regions, has been
      established. The pharmacological profile of GABA(C) receptors has been refined
      and more specific drugs have been developed. Molecular determinants that underlie
      functional properties of the receptors have been assigned to specific amino acid
      residues in rho-subunits. This information has helped determine the subunit
      composition of native receptors, as well as the molecular basis underlying subtle
      variations among GABA(C) receptors in different species. Finally, GABA(C)
      receptors play a unique functional role in retinal signal processing via three
      mechanisms: (1) slow activation; (2) segregation from other inhibitory receptors;
      and (3) contribution to multi-neuronal pathways.

PMID- 11239576
TI  - Orphan G-protein-coupled receptors and natural ligand discovery.
AB  - The superfamily of seven-transmembrane-domain G-protein-coupled receptors (GPCRs)
      is the largest and most diverse group of transmembrane proteins involved in
      signal transduction. Each of the approximately 1000 family members found in
      vertebrates responds to stimuli as diverse as hormones, neurotransmitters,
      odorants and light, which selectively activate intracellular signaling events
      mediated by heterotrimeric G proteins. Because GPCRs are centrally positioned in
      the plasma membrane to initiate a cascade of cellular responses by diverse
      extracellular mediators, it is not surprising that modulation of GPCR function
      has been successful in the development of many marketed therapeutic agents. It
      has become clear that GPCRs for which a natural activating ligand has not yet
      been identified (orphan GPCRs) might provide a path to discovering new cellular
      substances that are important in human physiology. The process of 'de
      orphanizing' these novel proteins has accelerated significantly and opened up new
      avenues for research in human physiology and pharmacology.

PMID- 11239577
TI  - Arylamine N-acetyltransferases - of mice, men and microorganisms.
AB  - Arylamine N-acetyltransferases (NATs) catalyse the transfer of an acetyl group
      from acetyl CoA to the terminal nitrogen of hydrazine and arylamine drugs and
      carcinogens. These enzymes are polymorphic and have an important place in the
      history of pharmacogenetics, being first identified as responsible for the
      polymorphic inactivation of the anti-tubercular drug isoniazid. NAT has recently
      been identified within Mycobacterium tuberculosis itself and is an important
      candidate for modulating the response of mycobacteria to isoniazid. The first
      three-dimensional structure of the unique NAT family shows the active-site
      cysteine to be aligned with conserved histidine and aspartate residues to form a
      catalytic triad, thus providing an activation mechanism for transfer of the
      acetyl group from acetyl CoA to cysteine. The unique fold could allow different
      members of the NAT family to play a variety of roles in endogenous and xenobiotic
      metabolism.

PMID- 11239578
TI  - Protease-activated receptors in inflammation, neuronal signaling and pain.
AB  - The ability of proteases to regulate cell function via protease-activated
      receptors (PARs) has led to new insights about the potential physiological
      functions of these enzymes. Several studies suggest that PARs play roles in both
      inflammation and tissue repair, depending on the cellular environment in which
      they act. The recent detection of PARs on peripheral and central neurons suggests
      that neuronal PARs might be involved not only in neurogenic inflammation and
      neurodegenerative processes, but also in nociception. Thus, the list of potential
      roles for PARs has lengthened considerably and their physiological course of
      action might be much broader than initially anticipated.

PMID- 11239579
TI  - Oestrogen and the cardiovascular system: the good, the bad and the puzzling.
AB  - The concept that oestrogen replacement therapy is cardioprotective has been
      challenged recently by the negative results of randomized clinical trials in
      coronary heart disease. These data have come at a time of rapid advances in our
      understanding of the cellular mechanisms of oestrogen. In particular, the cloning
      of the classical oestrogen receptor (ERalpha), the identification of a novel ER
      isoform (ERbeta), the availability of specific ERalpha and ERbeta knockout mice
      models, and the elucidation of receptor functions and signalling pathways linked
      to non-genomic actions of oestrogen are helping to unravel this complex biology.
      In this article, these advances will be discussed with particular emphasis on the
      regulation of nitric oxide synthesis by oestrogen. Furthermore, the puzzling
      issues that have emerged and the potential for development of novel and specific
      therapeutic approaches will be highlighted.

PMID- 11239581
TI  - Dental caries-protective agents in milk and milk products: investigations in
      vitro.
AB  - OBJECTIVES: To characterise and identify the anti-dental caries components that
      exist in milk and milk products. METHODS: Standard enamel or hydroxyapatite
      demineralisation tests were devised to simulate the action of acid on tooth
      mineral, and they were used to show which constituents of milk possessed a
      potential protective action against acid attack. RESULTS: Milk and milk products
      were fractionated and tested, revealing that minerals, including calcium and
      phosphorus, played a part in this protective process. The findings also drew
      attention to the effectiveness of minor milk protein or protein-associated
      components, the structures of which are mostly known, which were separated and
      characterised by gel electrophoresis as proteose-peptone fractions 3 and 5. The
      strength of adsorption of the protein or polypeptides in these fractions to
      dental enamel was measured and found to be sufficient to reduce the extent of
      demineralisation of enamel by acid buffer solutions. CONCLUSIONS: The removal of
      lactose, fat, casein and other proteins had little influence on the protective
      effect of the milk fractions. Besides calcium and phosphorus, milk contains other
      more powerful protective factors, which were identified as proteose-peptone
      fractions 3 and 5. Details of their composition and the strength of their
      adherence to the surface of dental mineral are given.

PMID- 11239582
TI  - The relationship between headache and symptoms of temporomandibular disorder in
      the general population.
AB  - OBJECTIVES: To describe the relationship between headache and symptoms of
      temporomandibular disorder (TMD) in a general population, and to assess whether
      there are specific symptoms associated with headache. METHODS: A personal
      interview survey conducted in 1995 on 483 adult subjects from the metropolitan
      community of Segrate, northern Italy. RESULTS: The overall prevalence of headache
      in the past year was 21.2%. The prevalence of temporomandibular symptoms was
      54.3%. Headache occurred significantly more in females than males (26.5 vs
      15.4%), and in subjects with, rather than without, symptoms of TMD (27.4 vs
      15.2%). Among symptoms, temporomandibular pain, temporomandibular joint sounds,
      and pain on movements of the jaw were associated with headache using a univariate
      analysis. After adjustment for confounding variables, a multiple logistic
      regression confirmed a significant relationship of headache with
      temporomandibular pain (OR 1.83, 95% CI, 1.07-3.15). CONCLUSIONS: In the general
      adult population there is an association between headache and symptoms of TMD. A
      functional evaluation of the stomatognathic system should be therefore considered
      in subjects with unexplained headache, even if chronic conditions and mechanical
      symptoms of temporomandibular disorder are absent.

PMID- 11239583
TI  - The propensity of individual saliva to cause extrinsic staining in vitro--a
      developmental method.
AB  - OBJECTIVES: To detect any differences in the propensity of individual saliva to
      cause in vitro staining by chlorhexidine and tea. METHODS: Unstimulated human
      saliva was collected on a daily basis and used to coat optically clear Perspex
      specimens. Specimens were subjected to the original chlorhexidine/tea staining
      model described by Prayitno and Addy (Journal of Periodontal Research 1979;14:397
      402), and cycles repeated until a maximum optical density of two was reached.
      RESULTS: Stain development increased incrementally with increasing cycles.
      Differences in chlorhexidine/tea staining between subjects were obvious by cycle
      3 where the lowest 'stainer' had 56% less stain than the highest 'stainer'.
      Highly significant differences between subjects were seen during staining cycles
      3-6, but not at cycles 7 and 8. CONCLUSIONS: In vitro stain formation using
      saliva from different individuals occurred at differing rates when all other
      variables were standardised. The properties of saliva accounting for this are
      still unknown, and warrant further study.

PMID- 11239584
TI  - Investigation of an index to measure tooth wear in primary teeth.
AB  - Tooth wear, in particular erosion, has been reported to be widespread in children
      in the UK. Wear may affect either dentition, but epidemiological measurement has
      proved difficult. OBJECTIVES: The objectives of this study were: (a) to
      investigate use of a simple index of wear in primary teeth; and (b) to compare
      findings from visual examination and from photographs with those at histological
      examination of the same teeth. SAMPLE AND METHODS: Forty-one exfoliated or
      extracted primary anterior teeth were assessed visually and using photographs.
      Ground sections of the teeth were prepared and examined using polarised light
      microscopy. RESULTS: On visual examination, 31 of the 41 teeth had evidence of
      wear. In 14 teeth, tissue loss was confined to enamel and in 17 it extended into
      dentine. Findings on photographs were very similar to those on visual
      examination. Of the 10 teeth without erosion visually, two had evidence of loss
      on histological examination. Of the 14 with visual evidence of erosion confined
      to enamel, dentine was exposed in 11 cases. Diffuse demineralisation was evident
      histologically in 11 of the 31 teeth with evidence of erosion. CONCLUSIONS: It
      was concluded that clinical assessment of erosion may underestimate the extent of
      the condition. Under the conditions of the study, photographs gave results
      similar to those on visual examination.

PMID- 11239585
TI  - The effect of cavity restoration variables on odontoblast cell numbers and dental
      repair.
AB  - OBJECTIVES: Dentinal repair following cavity restoration is dependent on several
      parameters including the numbers of surviving odontoblasts. The purpose of this
      study was to examine the effects of cavity cutting and restoration treatments on
      post-operative odontoblast numbers. METHODS: 353 Standardised non-exposed
      rectangular Class V cavities, were cut into the buccal dentin of intact 1st or
      2nd premolar teeth of 165 patients, aged between nine and 25 years of age.
      Composite cavity restorations with various etching treatments were compared with
      resin-modified glass ionomer cements, enamel bonding resins, as well as
      polycarboxylate, calcium hydroxide, and zinc oxide eugenol materials. Following
      tooth extraction (20-381 days) for orthodontic reasons, the area of the
      reactionary dentine and the area of the odontoblasts was measured
      histomorphometrically. RESULTS: Odontoblast numbers and dentine repair activity
      were found to be influenced more by cavity restoration variables, than the choice
      of cavity filling materials or patient factors. The most important cavity
      preparation variable was the cavity remaining dentine thickness (RDT); below
      0.25mm the numbers of odontoblasts decreased by 23%, and minimal reactionary
      dentine repair was observed. CONCLUSIONS: Odontoblast injury increased as the
      cavity RDT decreased. In rank order of maintaining odontoblast numbers beneath
      restored cavities with a RDT below 0.5mm, and using calcium hydroxide for
      comparison; calcium hydroxide (100%), polycarboxylate (82.4%), zinc oxide eugenol
      (81.3%), composite (75.5%), enamel bonding resin (49.5%) and RMGIC (42.8%). The
      vitality and dentine repair capacity of the pulp is dependent on odontoblast
      survival. Variations in the extent of odontoblast injury caused during operative
      procedures, may be the major underlying reason for the success or failure of
      restorative treatments.

PMID- 11239586
TI  - Inhibition of bacterial and glucan adherence to various light-cured fluoride
      releasing restorative materials.
AB  - OBJECTIVES: This study investigated the potential plaque adhesion properties of
      various light-cured fluoride-releasing restorative materials by measuring the
      amount of adhering radiolabeled bacteria and glucan. METHODS: Three resin
      modified glass ionomer cements (RMGI) and two polyacid-modified resin composites
      (compomer) were used in this study. As a control, one light-cured resin composite
      was added. Disk-shaped specimens were made following the manufacturers'
      recommendations and the respective surfaces were finished with a 600-grit
      abrasive paper. Streptococcus sobrinus B13 was selected as a cariogenic bacterial
      strain. The amount of bacteria and glucan adhered to these specimens were
      measured after 3, 8 and 24h incubations with radiolabeled cariogenic bacteria and
      sucrose. RESULTS: After 3 and 8h incubations, the amount of adhered bacteria and
      glucan was small and there were no significant differences among the restorative
      materials except in the resin composite. Although after 24h incubation the
      amounts of adhered bacteria and glucan, significantly increased on the RMGIs and
      compomers, these were still significantly less than the resin composite except
      one compomer. Although at 3h no good correlation was found between the contact
      angles and the amount of bacteria and glucans, the correlation coefficients were
      high at 8 or 24h. In addition, the coefficients for bacteria were always higher
      than those for glucan irrespective of the incubation times. CONCLUSIONS: After
      24h resin-modified glass ionomer cements and compomers showed significantly
      smaller amounts of adhered bacteria and glucans compared to resin composite with
      an exception of glucan adherence on one compomer.

PMID- 11239587
TI  - Marginal quality and microleakage of adhesive class V restorations.
AB  - OBJECTIVES: The aim of this in vitro study was to determine the marginal quality
      and microleakage of composite resin class V restorations. METHODS: Standardized
      mixed class V cavities (diameter: 4mm, depth: 2mm) with half of the finish lines
      limited within dentin were cut in 90 freshly extracted human molars and randomly
      assigned to nine groups (n=10). After etching enamel and dentin, the cavities
      were restored with nine different restorative systems (Syntac Sprint/Tetric
      Ceram=SS, Syntac Single-Component/Tetric Ceram=SC, Onestep/Aeliteflo=OS,
      Aquaprep+Onestep/Aeliteflo=OA, Prime & Bond 2.1/TPH=PB, Optibond Solo/Prodigy=OP,
      Singlebond/Z100=SB, Tenure Quik/Marathon=TQ, Solobond M/Arabesk=SM) using a wet
      bonding procedure. After finishing and polishing, the teeth were stored for 24h
      in distilled water at 37 degrees C before they were subjected to thermocycling
      (5/55 degrees C, 1000x). Epoxy replicas were made for margin analysis in the SEM.
      Specimens were stained in methylene blue, sectioned, and evaluated for
      microleakage. Dye penetration was scored on a 0-3 ordinal scale. RESULTS:
      Statistical analysis (Kruskal-Wallis H-test, Mann-Whitney U-test) revealed
      significant differences (P<0.05) among the groups at dentin and enamel margins
      for the microleakage scores as well as for the results of the quantitative SEM
      margin analysis. SC revealed a significantly higher percentage of perfect margins
      in the SEM than OS and SM in enamel and dentin, respectively. OA exhibited
      significantly more leakage in enamel than all other groups. CONCLUSIONS: None of
      the tested restorative systems achieved a perfect seal in dentin and enamel of
      mixed class V cavities. Marginal quality and sealing ability of adhesive systems
      to dentin, using a wet-bonding procedure, is still inferior compared with enamel
      margins.

PMID- 11239588
TI  - The evaluation of four conditioners for glass ionomer cements using field
      emission scanning electron microscopy.
AB  - OBJECTIVES: The purpose of this study was to evaluate the GIC-dentine interface
      morphology using FE-SEM after four different conditioners (Ketac Conditioner,
      Dentin Conditioner, Cavity Conditioner, and an experimental conditioner K-930),
      used with two RM-GICs and one self-cured GIC, and to observe the effect with an
      AFM of the four different conditioners on the surface of polished human dentine.
      MATERIALS AND METHODS: SAMPLE PREPARATION FOR FE-SEM: Twenty-four 1-mm thick
      dentine discs were obtained from superficial occlusal dentine of extracted human
      third molars, and finished with wet 600-grit SiC paper. The discs were treated
      for each of the GICs using the conditioners according to the manufacturers'
      instructions. The specimens were kept in tap water for 24 h at 37 degrees C, and
      then assigned for one of two observational techniques; a fractured technique and
      an acid-base technique. Specimens were mounted on aluminium stubs, gold sputter
      coated and observed using a FE-SEM. SAMPLE PREPARATION FOR AFM: Four rectangular
      dentine blocks approximately 2mm(3) were prepared from two extracted human third
      molars, polished and finished with diamond paste down to 0.25 microm particle
      size. One half of each sample was treated with one of the conditioners according
      to the manufacturers' instructions, and the other half was not conditioned. The
      samples were stored in distilled water prior to AFM contact mode observation.
      RESULTS: FE-SEM: All specimens of all materials demonstrated good adaptation to
      the underlying dentine. However, the specimens conditioned with K-930 showed
      increased demineralization and a thicker acid-base resistant layer (2.8-3.4
      microm) compared with the others (1-2 microm). AFM: The images of conditioned
      specimens showed demineralization of peritubular dentine. Funneling of dentinal
      tubule orifices of specimens conditioned with K-930 was observed, and was also
      seen for the FE-SEM specimens. SIGNIFICANCE: The use of surface conditioners
      resulted in similar adaptation to the non-conditioned specimens at the GIC
      dentine interface. All of the GICs demonstrated intimate adaptation to the
      dentine surface whether it was conditioned or not.

PMID- 11239589
TI  - Shear bond strengths of three resin cements to dentine over 3 years in vitro.
AB  - OBJECTIVES: This study was conducted to evaluate the bond durability of three
      resin cements bonded to bovine dentine over a period of 3 years. METHODS: Ten
      bovine dentine specimens were tested for shear bond strengths with each of the
      following materials: Panavia 21, BISTITE resin cement, and MASA Bond
      (experimental resin cement) at 1 day, 6 months, 1 and 3 years after cementation
      of a composite rod. All specimens were stressed in shear at a crosshead speed of
      1mm min(-1) until failure. The means of the bond strengths were compared
      statistically by two-way ANOVA and Fisher's PLSD test (P<0.05). The mode of
      failure was classified after fracture of the bonds by SEM observation. Results
      for the mode of fracture were analyzed using the Mann-Whitney U-test. RESULTS:
      The shear bond strengths (MPa+/-SD) for different times (1 day, 6 months, 1 and 3
      years) were: Panavia 21 (15.2+/-3.6, 9.3+/-3.2, 8.5+/-2.1, 6.8+/-2.4), BISTITE
      (15.6+/-2.8, 11.0+/-1.4, 10.4+/-2.2, 9.0+/-2.7) and MASA Bond (29.6+/-9.5, 17.5+/
      4.6, 19.6+/-4.5, 16.1+/-5.4). Panavia 21 and BISTITE strengths were significantly
      lower (P<0.05) at all times compared with MASA Bond, and 1 day strengths for all
      three materials were significantly higher (P<0.05) than 3 year strengths.
      Regarding the fracture modes after bond testing, there were statistical
      differences between the 1 day and the 1 year results for all cements (P<0.05).
      Although no Panavia 21 specimen showed complete cohesive failure in the
      demineralized dentine during the experiment, several BISTITE and MASA Bond
      specimens showed cohesive fracture in the demineralized dentine. For BISTITE,
      partially or complete demineralized dentine cohesive failures increased over
      time. CONCLUSIONS: The type of resin cement seemed to have an influence on the
      long-term durability of bonding to dentine.

PMID- 11239590
TI  - Association between microtensile bond strength and leakage in the indirect resin
      composite/dentin adhesively bonded joint.
AB  - PURPOSE: Develop a methodology to correlate microtensile bond strength (microTBS)
      and leakage within the same site of a specimen and evaluate the predominate
      debond and leakage pathways. MATERIALS AND METHODS: A Class II (MO) slot cavity
      was prepared in 37 extracted human molars and restored with indirect resin
      composite restorations. The restored teeth were thermocycled 300X between 5 and
      55 degrees C and then stained with silver. Two specimens per tooth were obtained
      by diamond saw sectioning for measurement of leakage (microm) and microtensile
      bond strength (MPa) at the gingival wall and then tested for association with
      regression analysis. Scanning electron microscopy techniques and energy
      dispersive spectroscopy (EDS) were used to evaluate the debond and leakage
      pathways. RESULTS: Association between leakage and bond strength was not
      significant (t=1.31, p=0.198). All 74 samples debonded within the joint,
      predominantly at the hybrid layer-adhesive resin region with only one specimen
      including a small portion of resin cement in the debond pathway. Secondary and
      backscatter imaging and EDS analysis showed leakage in all samples that involved
      the hybrid layer. CONCLUSION: This study demonstrates a feasible method for
      evaluating leakage and bond strength at the joint interface within the same
      specimen.

PMID- 11239592
TI  - Quest for antimicrobial genes to engineer disease-resistant crops.
AB  - Antimicrobial peptides are ancient mediators of the innate defenses of all
      species of life. These small lytic peptides are being exploited to genetically
      engineer disease-resistant crop plants. It is anticipated that certain
      (combinations of) potent antimicrobial peptides will provide agronomically
      relevant levels of disease control and should contribute to more sustainable
      agricultural practices.

PMID- 11239591
TI  - RNA polymerase I holoenzymes.
AB  - In eukaryotes, holoenzymes are large preassembled complexes containing RNA
      polymerases and variable sets of general transcription initiation factors and
      cofactors that are important for the regulation of gene expression. Recent
      advances in purification and characterization of RNA polymerase I holoenzyme from
      plants provide experimental data suggesting that it plays a key role in
      transcriptional regulation. These findings have a significant implication on our
      understanding of the mechanisms of promoter recognition, assembly of
      transcription initiation complexes, RNA chain elongation and transcription
      termination.

PMID- 11239594
TI  - Three defensive openings: AtCNGC2 and plant responses to pathogens.

PMID- 11239595
TI  - Circadian maestro leads plant gene expression symphony.

PMID- 11239596
TI  - Zipping between transcription factors: the ABA transduction pathway.

PMID- 11239607
TI  - Vacuolar H+/Ca2+ transport: who's directing the traffic?
AB  - Physiological studies have established the role of plant high-capacity vacuolar
      H+/Ca2+ exchange activity in ion homeostasis and signal transduction. The
      molecular characterization and structure-function analyses of these transporters
      are just beginning to emerge. In yeast, Ca2+ signaling molecules regulate
      vacuolar H+/Ca2+ exchange. Recently, some of the Ca2+ dependent "molecular relay"
      molecules have been characterized in plants; however, the regulation of plant
      vacuolar H+/Ca2+ exchange remains an open question.

PMID- 11239608
TI  - Motile plant cell body: a "bug" within a "cage".
AB  - Analysis of the cytoskeleton in morphogenetically active plant cells allows us to
      propose a unified concept for the structural organization of eukaryotic cells.
      Their cytoarchitecture is determined by two principal structural complexes:
      nucleus-microtubule-based cell bodies ("bugs") and plasma-membrane-F-actin-based
      cell periphery complexes ("cages"). There are dynamic interactions between each
      of these entities in response to extracellular and intracellular signals. In the
      case of the cell body, these signals determine its polarization, rotation and
      migration. Interactions between cell body and cell periphery complexes determine
      cell growth polarity and morphogenesis throughout the eukaryotic kingdom.

PMID- 11239609
TI  - Significance of epidermal fusion and intercalary growth for angiosperm evolution.
AB  - The ancestral angiosperm flower probably had many separate elements in each
      floral whorl (sepals, petals, stamens and carpels). Derived character states
      include "fusion" of elements within a whorl (cohesion) and fusion between whorls
      (adhesion), as well as epigyny and the emergence of the other floral elements
      from the apex of the fused carpels. This article considers the roles of epidermal
      fusion and intercalary growth in the phylogeny and ontogeny of fused floral
      elements, and the importance of fusion for angiosperm evolution.

PMID- 11239610
TI  - Plant meiosis: the means to 1N.
AB  - Meiosis is pivotal in the life history of plants. In addition to providing an
      opportunity for genetic reassortment, it marks the transition from diploid
      sporophyte to haploid gametophyte. Recent molecular data suggest that, like
      animals, plants possess a common set of genes (also conserved in eukaryotic
      microorganisms) responsible for meiotic recombination and chromosome segregation.
      However, unlike animals, plant meiocytes do not differentiate from a pool of
      primordial germ cells, but rather arise de novo from a germline formed from sub
      epidermal cells in the anthers and ovules. Mutants defective in the specification
      of these reproductive cell lines and disrupted in different aspects of the
      meiotic process are beginning to reveal many features unique to plant meiosis.

PMID- 11239611
TI  - Physiological mechanisms influencing plant nitrogen isotope composition.
AB  - Whole-plant and leaf nitrogen isotope composition are determined by the isotope
      ratio of the external nitrogen source and physiological mechanisms within the
      plant. Whole-plant isotope composition can reflect that of the nitrogen source
      when plant demand exceeds nitrogen supply. Uptake by mycorrhizae can cause the
      isotope ratio of the plant to deviate from the source. Intra-plant variation in
      isotope composition can be caused by multiple assimilation events, organ-specific
      loss of nitrogen, and resorption and reallocation of nitrogen. Future work must
      address acquisition of organic nitrogen from the soil solution, the role of
      mycorrhizae, and internal transformations within the plant.

PMID- 11239612
TI  - Applications of retrotransposons as genetic tools in plant biology.
AB  - Retrotransposons are mobile genetic elements that accomplish transposition via an
      RNA intermediate that is reverse transcribed before integration into a new
      location within the host genome. They are ubiquitous in eukaryotic organisms and
      constitute a major portion of the nuclear genome (often more than half of the
      total DNA) in plants. Furthermore, they are dispersed as interspersed repetitive
      sequences throughout most of the length of all host chromosomes. These unique
      properties of retrotransposons have been exploited as genetic tools for plant
      genome analysis. Major applications are in determining phylogeny and genetic
      diversity and in the functional analyses of genes in plants. Here, recent
      advances in molecular markers, gene tagging and functional genomics technologies
      using plant retrotransposons are described.

PMID- 11239613
TI  - Menstruation: choosing whether...and when.
AB  - For many women in the United States, menstruation is a major health concern
      because menstrual disorders and other conditions that may be aggravated during
      menses (e.g., migraine headaches, epilepsy) carry substantial morbidity. Women
      today menstruate nearly 3 times as often as in primitive societies, and evidence
      suggests that frequent, repetitive menstrual cycles may increase health risks.
      Because the conventional 21/7 combination oral contraceptive (OC) regimen
      provides only limited relief for women with menstrual disorders, alternative OC
      regimens that reduce menstrual frequency have been proposed. A new OC formulation
      specifically designed to decrease menstrual bleeding to 4 times per year is
      currently under investigation. Most women welcome less frequent menses or even
      amenorrhea. Women who may derive particular benefit from reduced menstrual
      frequency include not only those with medical conditions directly caused or
      aggravated by menses, but also those serving in the military, female athletes,
      mentally-retarded women with menstrual hygiene problems, young teens, and
      perimenopausal women.

PMID- 11239614
TI  - Low-dose oral contraceptives: health consequences of discontinuation.
AB  - Presently, the lowest effective estrogen dose available as a combination oral
      contraceptive (OC) in the United States is 20 microg of ethinyl estradiol (EE)
      with different progestins. Twenty micrograms of EE coupled with levonorgestrel
      results in fewer side effects and cycle control comparable with higher-dose
      pills. Differences between therapeutically equivalent and brand-name, low-dose
      oral contraceptives, with respect to the bioavailability of hormones, may
      interfere with contraceptive efficacy and increase breakthrough bleeding. One of
      the most common reasons why women discontinue OCs is increased breakthrough
      bleeding. Because after OC discontinuation most women switch to a less-effective
      method, or no method, of contraception, an increase in breakthrough bleeding
      could ultimately result in an increase in unintended pregnancy. Thus,
      substituting a therapeutically equivalent for a brand-name low-dose oral
      contraceptive may have significant clinical and economic effects on individual
      and public health.

PMID- 11239615
TI  - Bleeding patterns of women using Lunelle monthly contraceptive injections
      (medroxyprogesterone acetate and estradiol cypionate injectable suspension)
      compared with those of women using Ortho-Novum 7/7/7 (norethindrone/ethinyl
      estradiol triphasic) or other oral contraceptives.
AB  - Persistent and/or unpredictable bleeding is a common reason for discontinuation
      of hormonal contraceptive methods. An open-label, nonrandomized, parallel,
      controlled study compared the efficacy, safety, and cycle control of the new,
      highly efficacious monthly injectable contraceptive containing 25 mg
      medroxyprogesterone acetate (MPA) and 5 mg estradiol cypionate (E(2)C)
      (MPA/E(2)C) (Lunelle Monthly Contraceptive Injection) with that of the frequently
      used norethindrone 0.5, 0.75, 1.0 mg/0.035 mg ethinyl estradiol (NET/EE)
      triphasic oral contraceptive (Ortho-Novum 7/7/7). This report directly compares
      the bleeding patterns of women on MPA/E(2)C to those of women on NET/EE and
      untreated women. Overall, breakthrough bleeding occurred less frequently in women
      using MPA/E(2)C than in women using NET/EE (p < or =0.01). However, more women
      using MPA/E(2)C experienced amenorrhea/missed periods than those on NET/EE (p <
      or =0.01). In addition, the percentage of women experiencing breakthrough
      bleeding or amenorrhea while using other oral contraceptives is compared to that
      of women using MPA/E(2)C. A rapidly reversible method, MPA/E(2)C, combines the
      high contraceptive efficacy of surgical sterilization with the convenience of
      monthly administration. These data suggest that, for a large proportion of women,
      MPA/E(2)C offers predictability in bleeding patterns comparable to or greater
      than that experienced by ovulatory untreated women or those using combination
      oral contraceptives.

PMID- 11239616
TI  - Parity is a major determinant of success rate in medical abortion: a
      retrospective analysis of 3161 consecutive cases of early medical abortion
      treated with reduced doses of mifepristone and vaginal gemeprost.
AB  - The antiprogesterone mifepristone in combination with a suitable prostaglandin
      provides an effective method for induction of abortion in early pregnancy up to
      63 days of gestation. The combination of 600 mg mifepristone followed by 1 mg of
      gemeprost vaginal pessary 48 h later is one of the standard regimens in practice,
      which is registered in several countries in Europe. In 1995, we reduced the doses
      for both mifepristone and gemeprost to 200 mg and 0.5 mg respectively, as this
      was shown to decrease significantly the incidence of side effects whilst
      maintaining a high efficacy. In this article, we report our experience with this
      regimen in routine clinical practice by analysing 3161 consecutive medical
      abortions retrospectively. Twelve case notes (0.4%) were not available, and for
      310 (9.8%) women, the outcome was not known with certainty as they did not return
      for their follow up visit. Of the remaining 2839 women, 2732 (96.2%) had a
      complete abortion following their treatment. One-hundred-two (3.6%) women
      required an evacuation of the uterus: for incomplete abortion in 63 (2.2%) and
      ongoing pregnancy in 39 (1.4%). Three women had to undergo surgery for ectopic
      pregnancies. The surgical intervention rate was significantly higher at gestation
      of >49 days compared to < or = 49 days (5.7% vs. 2.6%, p = 0.002) and at >56 days
      than among those at < or = 56 days (6.7% vs. 3.1%; p <0.001). However, for
      incomplete abortion a significant increase was only seen at gestation >49 days
      compared to < or = 49 days (3% vs. 1.6%, p = 0.017). The incidence of ongoing
      pregnancies increased significantly only after 56 days of gestation compared to <
      or = 56 days (3.8% vs. 0.9%; p <0.001). Parity was related to the outcome with
      parous women having significantly more incomplete/ongoing abortions compared to
      nulliparous women (5.4% vs. 2.0%; p <0.001), although parous women did present
      earlier in pregnancy for termination than nulliparous women (p = 0.01). The
      incidence of complications was low: 165 (5.8%) women were given antibiotics for
      presumed genital infection and severe haemorrhage occurred in 11 (0.4%) women, of
      whom only two required blood transfusion. In summary, the recommended regimen
      with the reduced doses of mifepristone and gemeprost is highly effective, meeting
      the anticipated efficacy with a complete abortion rate of >95%. We have concluded
      from the data that gestation and parity are strong predictors for clinicians to
      anticipate the probability of a successful medical termination of pregnancy.

PMID- 11239617
TI  - Timing of pain and bleeding after mifepristone-induced abortion.
AB  - Previous studies of medical abortion with mifepristone and a prostaglandin have
      reported percentages of subjects who experience cramping and/or bleeding relative
      to prostaglandin use. This is the first analysis of cramping and bleeding onset
      patterns in subjects treated with low-dose (200 mg) mifepristone and 800 microg
      vaginal misoprostol at 24, 48, or 72 h after mifepristone. We analyzed the
      cramping and bleeding onset patterns in subjects up to 8 weeks pregnant who used
      800 microg vaginal misoprostol at 24, 48, or 72 h after 200 mg of oral
      mifepristone. We collected data from subjects' symptom diaries and divided
      symptom onset into 3 categories: before misoprostol use, 0--12 h following
      misoprostol, and more than 12 h after misoprostol. Of the 2,302 subjects,
      cramping and bleeding onset data were available for 2,030 (88%) and 2,123 (92%),
      respectively. Across all groups, 230 (11%) experienced cramping and 445 (21%)
      experienced bleeding before misoprostol use. There was a significantly higher
      percentage of subjects who experienced early cramping and/or early bleeding
      between the three treatment groups, and this was related to the interval between
      mifepristone and misoprostol. In the 12 h following misoprostol administration,
      cramping and bleeding patterns were similar in the three groups. The longer
      subjects waited to insert misoprostol, the more likely they were to experience
      early cramping and/or bleeding. After misoprostol insertion, cramping and
      bleeding patterns are similar regardless of treatment group. Patients and
      providers cannot rely on symptom onset to predict treatment success.

PMID- 11239622
TI  - Effect of delayed metamorphosis on larval competence, and post-larval survival
      and growth, in the abalone Haliotis iris Gmelin.
AB  - Marine invertebrate species vary in their ability to delay metamorphosis, and in
      the degree to which delayed metamorphosis compromises juvenile performance.
      Abalone (Haliotis iris) larvae were deprived of metamorphosis cues and the
      effects of delayed metamorphosis on larval competence, and post-larval growth and
      survival were quantified. Larvae were exposed to a metamorphosis inducer (the
      coralline alga Phymatolithon repandum (Foslie) Wilks and Woelkerling) on Days 11,
      18, 22, 26, 30 and 34 post-fertilisation (temperature 16-17 degrees C). Post
      larvae were reared on diatoms (Nitzschia longissima Grunow) for 3-4 weeks post
      metamorphosis. Delayed metamorphosis caused progressive negative effects on post
      larval performance. Virtually all larvae initiated metamorphosis in response to
      P. repandum, regardless of larval age. The proportion of post-larvae that
      developed post-larval shell growth within 2 days of metamorphosis induction
      dropped only approximately 20% from Day 11 to Day 26 (P>0.05), but was
      significantly lower by Day 30 and Day 34 (P<0.001). Larvae that metamorphosed on
      Days 11, 18 and 22 showed high survival (>80%) and growth rates (means of 20-22
      um shell length per day). In contrast, larvae that metamorphosed on Day 26 and
      Day 30 had poor survival (30-40%) and lower (P<0.05) growth rates (15-16 um/day).
      Of the larvae that metamorphosed on Day 34, only 7 (30%) survived their first
      week post-metamorphosis, and they grew only 2 um/day on average. Only one of
      these post-larvae (4%) survived the second week. The visible yolk supply
      diminished over the life of the larvae and was near zero by Day 34. Nearly all
      larvae had died by Day 38. H. iris larvae remained competent to metamorphose for
      at least 3 weeks after they attained competence. Post-larval growth and survival
      were not reduced if metamorphosis occurred within 3 weeks of fertilisation. This
      extended period of larval competence implies that H. iris larvae can potentially
      disperse for up to several weeks before successful metamorphosis.

PMID- 11239620
TI  - Rheological properties of contraceptive gels.
AB  - The rheological properties of 4 commercially available contraceptive drug
      delivery gels and their dilutions with a vaginal fluid simulant were measured.
      These properties govern the critical functions of spreading and retention of
      these gels over the vaginal surfaces. Measurements made on Conceptrol, KY Plus,
      Gynol II, and Advantage-S included stress growth, stress relaxation and residual
      stress, and the shear rate dependence of viscosity. All gels exhibited non
      Newtonian behavior including shear thinning and viscoelasticity. Conceptrol and
      Gynol II had no residual stress, while both KY Plus and Advantage-S did. The gels
      differed in their response to dilution with vaginal fluid simulant.

PMID- 11239618
TI  - Analgesia during at-home use of misoprostol as part of a medical abortion
      regimen.
AB  - The objective of this study was to identify predictors of narcotic analgesic use
      during medical abortion. Two-thousand-seven-hundred-forty-seven women with
      pregnancies of 63 days gestational age or less received 200 mg mifepristone
      followed by at-home use of 800 microg vaginal misoprostol in two consecutive
      clinical trials in the United States, and also reported their use of analgesics.
      Overall, 79% of these subjects used narcotic analgesics. Women in the 2nd of the
      two studies were randomized to use misoprostol 24, 48, or 72 h after
      mifepristone. Those who were randomized to 24 h were more likely to use narcotic
      analgesics than those who were randomized to 48 or 72 h. In both studies, the use
      of narcotic analgesia during medical abortion was less prevalent among parous
      women and Asian women, and among those with a gestational age of 56 days or less.
      The clinic providing care for the patient was the most important determinant of
      narcotic analgesia use, even though the analgesia was used at home. Use of
      narcotic analgesics in these women undergoing medical abortion at home was more
      prevalent than use reported in previous studies where women underwent medical
      abortion in a clinical setting.

PMID- 11239619
TI  - How well do male latex condoms work? Pregnancy outcome during one menstrual cycle
      of use.
AB  - To evaluate the contraceptive effectiveness of male latex condoms, we assembled a
      cohort of 300 women relying on male latex condoms for contraception and followed
      them prospectively for one menstrual cycle. None of the 234 women who completed
      the study and reported at least one act of intercourse conceived (one cycle
      pregnancy rate 0%; 95% CI 0%--2%). Given the pattern of intercourse during the
      cycle and 3 different sets of conception probabilities for different days of the
      cycle, we would have expected between 32 and 36 pregnancies if no condoms had
      been used. Thus, the prevented fraction due to condom use (effectiveness) is 100%
      and the lower bounds of the 95% CI are between 89% and 90%. For this cohort, male
      latex condoms were an effective method of contraception. This cost-efficient
      approach of evaluating contraceptive effectiveness shows promise for post
      marketing studies.

PMID- 11239621
TI  - Effect of oral contraceptive steroid hormones on metabolic parameters of
      streptozotocin-induced diabetic rat.
AB  - This study examined the effect of 0.05 mg norgestrel + 0.01 ethinyl estradiol
      (NEE) Kg x body wt(-1) on body weight, random blood glucose, glycosylated
      hemoglobin, and plasma insulin levels in streptozotocin-induced diabetic rats.
      Weight loss, blood glucose, glycosylated hemoglobin, and plasma insulin values of
      rats treated with NEE before and after the onset of diabetes were not
      significantly different from that of untreated diabetic rats. In conclusion, oral
      administration of these contraceptive steroid hormones does not significantly
      alter the metabolic parameters of diabetic rats.

PMID- 11239623
TI  - Fish fauna of the Severn Estuary. Are there long-term changes in abundance and
      species composition and are the recruitment patterns of the main marine species
      correlated?
AB  - Fish were collected from the intake screens of the Oldbury Power Station in the
      Severn Estuary in each week between early July 1972 and late June 1977 and at
      least twice monthly between early January 1996 and late June 1999. The annual
      catches, after adjustment to a common sampling effort, demonstrate that the
      abundance of fish at Oldbury was far greater in the 1990s than 1970s, mainly due
      to marked increases in the numbers of certain marine species, such as sand goby,
      whiting, bass, thin-lipped grey mullet, herring, sprat and Norway pout. These
      increases may reflect the great improvement that occurred in the water quality of
      the Severn Estuary between these decades. The only species that declined markedly
      in abundance was poor cod. Modest declines in flounder and River lamprey
      paralleled those occurring elsewhere in the UK. The species composition in the
      two decades also differed, reflecting changes not only in the relative abundances
      of the various marine estuarine-opportunistic species, which dominated the
      ichthyofauna, but also in those of the suite of less abundant species in the
      estuary. The cyclical changes undergone each year by the species composition of
      the fish fauna of the Severn Estuary reflect sequential intra-annual changes in
      the relative abundances of species representing each of the marine, diadromous
      and freshwater categories. New approaches have been developed to test whether or
      not large sets of correlations between patterns of recruitment amongst abundant
      marine species (internal correlations), and between those patterns and salinity
      and water temperature within the estuary (cross-correlations), were significant.
      The correlation profile analyses found no evidence that the annual recruitment
      strengths of these species were either intercorrelated, or correlated with either
      one or a combination of both of the above environmental variables. Yet, the
      timings of the recruitment of these species into the estuary were
      intercorrelated, i.e. a slightly earlier or later than normal immigration by one
      species in a given year was paralleled by the same trend in other species.
      However, this association in recruitment times could be linked neither to
      salinity nor water temperature within the estuary, nor to a combination of these
      two variables. These results indicate that, while the factors that influence the
      annual recruitment strengths of the juveniles of different marine species vary,
      inter-annual differences in the phasing of events that regulate spawning times
      and/or larval dispersal influence, in the same direction, the times when marine
      species are recruited into the estuary.

PMID- 11239624
TI  - The competitive and predatory impacts of the nonindigenous crab Carcinus maenas
      (L.) on early benthic phase Dungeness crab Cancer magister Dana.
AB  - We evaluate the potential competitive and predatory impacts of nonindigenous
      European green crab Carcinus maenas on native Dungeness crab Cancer magister in
      the northeast Pacific. The coastal estuaries of Washington State, USA, provide
      appropriate habitat for recently introduced green crab, yet these areas are
      important nursery grounds for Dungeness crab and contribute greatly to the
      coastal crab fishery. Juvenile Dungeness crabs are dependent on limited
      intertidal epibenthic shell for refuge habitat during early benthic life and
      experience increased mortality on open sand and mud as a result of predation by
      fish and birds. Early juveniles throughout the subtidal are similarly at risk due
      to predation by fish and especially adult conspecifics. Laboratory experiments
      and infrared video observations revealed that juvenile green crab displace
      Dungeness crab of equal size from shelters during one-on-one competition. Green
      crab also consistently win nocturnal foraging trials in which the species compete
      for fresh, damaged clams. Field and laboratory enclosure experiments show that
      juvenile Dungeness crab emigrate from oyster shell habitat as a result of
      competition and predation by adult green crab. Depending on the extent to which
      the two species overlap, interactions with the dominant nonindigenous species
      could have a negative influence on juvenile Dungeness crab survival and could
      conceivably impact recruitment to the fishery. However, current evidence
      indicates that the distribution of green crab in Washington State is far removed
      from nursery areas of Dungeness crab.

PMID- 11239625
TI  - Effects of salinity, temperature and food level on the demographic
      characteristics of the seawater rotifer Synchaeta littoralis Rousselet.
AB  - A strain of the seawater species Synchaeta littoralis, isolated from a Spanish
      Mediterranean coastal salt marsh, was cultured in the laboratory and fed with the
      alga Tetraselmis sp. The effect of three salinities (25 per thousand, 30 per
      thousand and 35 per thousand), two temperatures (20 degrees C and 25 degrees C)
      and two food levels (75,000 and 150,000 cells ml(-1)) on demographic parameters
      was studied using a life table approach. Average lifespan (LS) ranged between 4.0
      and 7.3 days, net reproductive rate (R(0)) between 4.2 and 9.1 offspring per
      female, and intrinsic growth rate (r) between 0.50 and 0.95 day(-1). Salinity and
      temperature had a significant negative effect (***p<0.001) on both average
      lifespan (LS) and net reproductive rate (R(0)). Nevertheless, S. littoralis grew
      adequately at 35 per thousand (average value of r=0.67 day(-1)). Intrinsic growth
      rate also increased with temperature due to the lower value of the generation
      time (ranged between 2.3 and 3.8 days in all assays). Food level only had a
      significant negative effect (***p<0.001) on R(0). The experiments designed
      allowed us to know the basic demographic parameters of S. littoralis.

PMID- 11239626
TI  - The role of leaf nitrogen content in determining turtlegrass (Thalassia
      testudinum) grazing by a generalized herbivore in the northeastern Gulf of
      Mexico.
AB  - In shallow marine environments the variability in grazing on seagrasses has been
      hypothesized to be controlled, in part, by the nutritive quality (i.e., nitrogen
      content) of their leaves. The few existing studies of the relationship between
      leaf nitrogen content and seagrass grazing have all found a positive relationship
      between leaf nitrogen content and preference by selective vertebrate grazers
      (i.e., the bucktooth parrotfish, green sea turtles, and dugongs). However, most
      marine herbivores (both vertebrate and invertebrate) are thought to be extreme
      generalists with broad diets of variable nutritive quality (e.g., detritus,
      living plants, and animals), suggesting the currently held view on the role leaf
      nutrient content in explaining the variability of seagrass grazing is an
      oversimplification.In this study, we evaluated how leaf nitrogen content
      influenced grazing on turtlegrass by a generalist invertebrate herbivore (the
      pink sea urchin Lytechinus variegatus) in the northeastern Gulf of Mexico. Using
      a short-term laboratory test and a longer-term field experiment, we tested the
      hypothesis that leaf nitrogen content controls sea-urchin grazing on seagrass
      leaves. We hypothesized that if poor nutritive value of seagrasses is responsible
      for reduced rates of feeding, then increasing leaf nitrogen concentrations should
      lead to increased rates of seagrass consumption by sea urchins.In the field
      experiment, we significantly enriched seagrass leaf nitrogen concentrations (some
      10-20% depending on month) in experimental plots with a commercial fertilizer and
      we manipulated grazing intensity by enclosing adult sea urchins at densities that
      bracketed the range of average densities observed in the region (i.e., 0, 10 and
      20 individuals/m(2)). Comparisons of changes in aboveground seagrass production
      and biomass showed no evidence that sea urchins grazed significantly more in
      treatments where leaf nitrogen was enriched. Because the statistical power of our
      test to detect such differences was low and aboveground seagrass production
      varied significantly among treatments, we also used a mass balance equation to
      estimate sea urchin consumption of nitrogen-enriched and unenriched leaves. This
      showed that sea urchins compensated for low nitrogen levels in our unenriched
      treatments by eating more leaves than in treatments where leaf nitrogen was
      elevated. Using a laboratory test, we also found that sea urchins ate less
      nitrogen-enriched seagrass than unenriched seagrass. In combination, these
      results show that, in contrast to findings reported for vertebrate herbivores,
      sea urchins feed at higher rates when offered seagrass leaves of lower leaf
      nitrogen content, and that low levels of leaf nitrogen are not always an
      effective defense against herbivores.

PMID- 11239627
TI  - The relative influence of temperature and food on the metabolism of a marine
      invertebrate.
AB  - Many benthic marine invertebrates exhibit a seasonal cycle in activities such as
      feeding, growth and reproduction. In temperate regions, this seasonality is
      typically correlated with coincident cycles in photoperiod, temperature and food
      availability and it can be difficult to determine which of these environmental
      factors is the key driver. Polar regions are characterised by greatly reduced
      seasonal variation in temperature, and an enhanced seasonality of food
      availability; they therefore form a natural laboratory for distinguishing the
      ecological effects of food from those of temperature. Here, we report a study of
      the common shallow water urchin Sterechinus neumayeri from Rothera Point,
      Antarctica. This species exhibits a marked seasonal variation in metabolic rate
      and feeding activity (which ceases completely in winter). In this study the
      metabolic rate of urchins collected in late winter and held in the laboratory
      without food was compared with that of wild urchins undertaking the transition to
      summer feeding and growth. Starved urchins showed a small rise in metabolic rate
      in summer which could be explained entirely by the small increase in temperature
      (Q(10)=2.5). At the same time, the wild population showed a much larger increase
      in metabolic rate related largely to the costs of feeding and growth. Rates of
      nitrogen excretion were also much larger in wild urchins, and the O:N atomic
      ratio indicated that starved urchins were depending to a greater extent on lipid
      and carbohydrate. Gut mass and test organic content showed no change in starved
      urchins, indicating that metabolic substrate was being provided by the gonad. The
      data suggest that in wild S. neumayeri only 15-20% of the summer increase in
      metabolism is caused directly by the temperature rise whereas 80-85% is caused by
      increased physiological activity associated with feeding, growth and spawning.

PMID- 11239628
TI  - Small scale variability of benthic assemblages: biogenic neighborhood effects.
AB  - In this study, patterns of community development were investigated within vs.
      outside 'habitats'. These habitats represented five different monospecific
      assemblages of one of the following species: the brown alga Fucus serratus, the
      red alga Delesseria sanguinea, the green alga Enteromorpha intestinalis, the
      seagrass Zostera marina and the blue mussel Mytilus edulis. Natural assemblages
      were allowed to develop on paired artificial substrata-separated by ca. 1 m
      within (treatment) vs. outside (control) of habitats. The same colonizer species
      settled on treatment and control substrata for given habitats. However, after 5
      months of settlement and post-settlement dynamics, their proportional abundance
      and the structure of treatment and control assemblages differed in many
      instances. Variability among replicates of a given treatment, seperated by up to
      50 m, was large, indicating a patchy spatial distribution of organisms. Despite
      this spatial heterogeneity among within-treatment replicates, analysis of
      similarity revealed that in most instances significantly different assemblages
      developed between treatments on a small spatial scale depending on whether
      substrata were positioned within as compared to outside a given
      habitat.Consequently, the algae, seagrass or mussels constituting a habitat seem
      to control the structure of the benthic assemblage developing in their vicinity
      by one or more possible mechanisms: reduction of larval advection, exudation of
      metabolites that influence settlement and/or post-settlement survival, and/or-in
      the case of mussel assemblages-predation on larvae.In addition to spatial
      variability in larval supply, stochasticity in succession, substratum
      heterogeneity, competition and predation effects, this investigation reveals the
      potential of a further assemblage structuring factor: the impact of neighboring
      organisms.

PMID- 11239629
TI  - External and internal tags for the green sea urchin.
AB  - Two internal and three external tags were tested on the green sea urchin.
      Desirable qualities of a tag were high sea urchin survival, retention for at
      least a few months, detection on the sea floor by divers, identification of
      individuals, quick application, and low cost. These objectives were met by an
      external nylon screw tag visible to divers and two internal aluminum tags
      detectable with an underwater metal detector. Successful tags were inserted
      through a hole drilled in the test and were tested in the laboratory and field.
      All internal tags were retained for the full duration of the 4-month trial and
      did not retard growth or affect survival. Divers could identify individual
      urchins with nylon screw tags, but the tag retention rate was lower.

PMID- 11239630
TI  - Food supply, grazing activity and growth rate in the limpet Patella vulgata L.: a
      comparison between exposed and sheltered shores.
AB  - The limpet Patella vulgata L. is an important microphagous grazer on intertidal
      rocky shores of north-west Europe, occurring across the wave exposure gradient.
      Groups of P. vulgata were selected at mid-tide level of two exposed shores and
      two sheltered, fucoid dominated shores on the Isle of Man, British Isles, and
      manipulated to equivalent densities and population structure. The level of
      grazing activity and growth rate were determined over a 1-year period. At the
      same time, the abundance of epilithic microalgae, measured as the concentration
      of chlorophyll a, was determined as an estimate of food supply. Microagal
      abundance showed a seasonal pattern in both exposed and sheltered conditions,
      with higher levels in winter compared to summer. In both seasons, the microalgal
      resource was more abundant on the sheltered shore studied. The level of grazing
      activity in P. vulgata showed a seasonal pattern on the exposed but not the
      sheltered shores. Averaged over the year, grazing activity on the exposed shores
      was over double that on sheltered shores. Thus, in sheltered conditions, food
      supply for limpets was high and grazing activity low; in exposed conditions, food
      supply was low and grazing activity high. The growth rate of P. vulgata, measured
      as increase in shell length, showed no significant difference between exposed and
      sheltered shores. Growth rate was also determined in P. vulgata at natural
      densities. Although the overall density declined with decreasing exposure to wave
      action, the density per unit area of grazeable substance was higher in shelter.
      In these populations, the mean growth rate was over twice as high on exposed
      compared to sheltered shores.

PMID- 11239631
TI  - Carotid vascular resistance in long-term estrogen users.
AB  - OBJECTIVE: To compare carotid vascular resistance in long-term estrogen users
      with that of age-matched nonusers. METHODS: Pairwise comparisons between 18 long
      term users of 17beta-estradiol (E2) implants (mean age 67.8 years, mean duration
      of treatment 18.8 years, range 5.8-33.9 years) and 18 age-matched (+/- 2 years)
      nonusers. We used color Doppler ultrasound to assess pulsatility index (PI) and
      resistance index (RI) in common, external, and internal carotid arteries.
      RESULTS: Estrogen users compared with age-matched nonusers had significantly
      lower mean values for common carotid RI, -4%; -0.04 (95% confidence interval [CI]
      -0.07, -0.03, P =.036) and marginally significant for PI, -12%; -0.25 (95% CI 
      0.54, 0.04, P =.087). Differences in external and internal carotids were smaller
      and insignificant. Age was a determinant of internal carotid vascular resistance
      in estrogen users and nonusers. Increasing pairwise differences in external
      carotid vascular resistance with advancing age (r = 0.55; P =.02), with
      magnitudes of mean group differences indicate a modest but true effect of long
      term estrogen therapy on vascular resistance in common carotids, less in
      external, and negligible in internal carotid arteries. The study had an 80% power
      to detect a 10% mean difference (0.08 units) in common carotid RI at the 5%
      level. The standard deviation was considerably lower for estimates of RI than for
      PI. CONCLUSION: Long-term estrogen therapy was associated with minor reduction of
      vascular resistance in common carotid, less in external, and negligible in
      internal carotid arteries. Effects on carotid vascular resistance do not seem to
      be a major mechanism in the long-term protective effect of estrogen therapy on
      cardiovascular risk.

PMID- 11239632
TI  - Lipolytic enzyme effect on small low-density lipoprotein particles in women
      treated with estrogen.
AB  - OBJECTIVE: To test whether hydrolysis of low-density lipoprotein (LDL)
      triglyceride by lipolytic enzymes decreases the size of LDL particles in women
      treated with estrogen replacement. METHODS: Fifteen postmenopausal women received
      0.625 mg conjugated equine estrogens daily for 3 months. Plasma concentrations of
      total cholesterol, triglyceride, and high-density lipoprotein (HDL) cholesterol
      were measured before and after therapy. We also assayed levels of total, free,
      and esterified cholesterol, triglyceride, and protein in LDL. Plasma samples were
      incubated at 37C for 24 hours and LDL fractions were isolated by
      ultracentrifugation. After LDL samples were further incubated with or without
      lipoprotein lipase (500, 700, and 1000 ng/mL) at 37C for 24 hours, LDL
      triglyceride, LDL protein, and the diameter of LDL particles were measured.
      RESULTS: Estrogen decreased total cholesterol and increased triglyceride and HDL
      cholesterol in plasma. Estrogen treatment decreased the ratio of cholesteryl
      ester/protein, whereas the ratio of triglyceride/protein increased. Estrogen
      decreased LDL particle diameter. Incubation of plasma increased the ratio of LDL
      triglyceride/protein from 0.40 +/- 0.14 to 0.48 +/- 0.15 (P <.05) and decreased
      the ratio of LDL cholesteryl ester/protein from 1.17 +/- 0.25 to 1.09 +/- 0.22 (P
      <.05), but LDL particle diameter did not change. Incubation of LDL with
      lipoprotein lipase reduced the LDL triglyceride/protein ratio, and decreased the
      diameter of LDL particles from 25.61 +/- 0.87 nm to 24.89 +/- 0.88 nm (500 ng/mL,
      P <.05), 24.62 +/- 1.20 nm (700 ng/mL, P <.05), and 24.67 +/- 1.19 nm (1000
      ng/mL, P <.05). CONCLUSION: In women treated with estrogen, hydrolysis of
      triglyceride in LDL particles might be accompanied by reduced particle size.

PMID- 11239633
TI  - Body fat distribution and body composition during GnRH agonist therapy.
AB  - OBJECTIVE: To identify the effects of GnRH agonist therapy on body composition
      (lean and fat mass components) and body fat distribution. METHODS: Fifteen women
      with uterine leiomyomas were given a GnRH agonist (leuprorelin acetate, 3.75 mg)
      monthly for 4 months. Weight, height, and body mass index (BMI, weight/height)
      were recorded. Regional and total body composition, trunk-leg fat ratio, bone
      mineral density of the lumbar spine (L2-L4), and total body were assessed by
      whole-body scanning with dual-energy x-ray absorptiometry before and after
      treatment. Uterine volume was measured by transabdominal ultrasonography.
      RESULTS: The mean (+/- standard deviation [SD]) lean mass of total body, trunk,
      and leg decreased significantly (36.3 +/- 4.9 to 35.4 +/- 4.4 kg, P <.01; 18.8 +/
      2.8 to 18.1 +/- 2.8 kg, P <.05; and 11.4 +/- 1.8 to 11.1 +/- 1.6 kg, P <.05;
      respectively), whereas body fat mass, percentage of body fat, and trunk fat mass
      increased significantly (20.8 +/- 4.8 to 21.8 +/- 4.6 kg, P <.01; 34.9 +/- 5.9 to
      36.5 +/- 5.2%, P <.01; and 8.6 +/- 3.0 to 9.3 +/- 3.0 kg, P <.01; respectively).
      Trunk-leg fat ratio increased significantly (1.03 +/- 0.32 to 1.12 +/- 0.33, P
      <.05). Weight, BMI, arm tissue composition (lean and fat mass components), and
      leg fat mass did not change during 4 months of GnRH agonist therapy. Bone mineral
      density and uterine volume decreased significantly. CONCLUSION: Hypogonadism by
      GnRH agonist therapy induces lean mass loss, increased adiposity overall, and
      upper body fat accumulation.

PMID- 11239634
TI  - Continuous low-level topical heat in the treatment of dysmenorrhea.
AB  - OBJECTIVE: To compare the efficacy of topically applied heat for menstrual pain
      with oral ibuprofen and placebo treatment. METHODS: We conducted a randomized
      placebo and active controlled (double dummy), parallel study using an abdominal
      patch (heated or unheated) for approximately 12 consecutive hours per day and
      oral medication (placebo or ibuprofen 400 mg) three times daily, approximately 6
      hours apart for 2 consecutive days. Pain relief and pain intensity were recorded
      at 17 time points. There was at least 85% power to detect a true one-unit
      difference in the 2-day pain relief treatment means for comparisons with the
      unheated patch plus oral placebo group using a one-tailed test at the.05 level of
      significance, based on an observed within-group standard deviation of 1.147.
      RESULTS: Eighty-four patients were enrolled and 81 completed the study protocol.
      Over the 2 days of treatment, the heated patch plus placebo tablet group (mean
      3.27, P <.001), the unheated patch plus ibuprofen group (mean 3.07, P =.001), and
      the combination heated patch plus ibuprofen group (mean 3.55, P <.001) had
      significantly greater pain relief than the unheated patch plus placebo group
      (mean 1.95). Greater pain relief was not observed for the combination heated
      patch plus ibuprofen group compared with the unheated patch plus ibuprofen group
      (P =.096); however, the time to noticeable pain relief was statistically
      significantly shorter for the heated patch plus ibuprofen group (median 1.5
      hours) compared with the unheated patch plus ibuprofen group (median 2.79 hours,
      P =.01). CONCLUSION: Continuous low-level topical heat therapy was as effective
      as ibuprofen for the treatment of dysmenorrhea.

PMID- 11239635
TI  - Parturition and urinary incontinence in primiparas.
AB  - OBJECTIVE: To estimate the incidence and relative risk of postpartum urinary
      incontinence in primiparas. METHODS: Over 3 years (1996-1998), healthy nulliparas
      with no significant history of urinary tract abnormalities were prospectively
      enrolled. Power analysis indicated that 452 women must complete the study.
      Participants completed a questionnaire about urinary, fecal, and flatal
      incontinence. At 6 weeks' and 6 months' postpartum, the same questionnaire was
      mailed to participants. Statistical analysis consisted of chi-square and Fisher
      exact tests for nominal variables and analysis of variance and Kruskal-Wallis
      tests for interval variables. Logistic regression tested independence of
      variables. RESULTS: A total of 690 primiparas were enrolled in the study and 595
      delivered at our hospital: 147 (25%) cesareans, 333 (56%) spontaneous vaginal
      deliveries, and 115 (19%) instrumental vaginal deliveries. Median birth weight
      was 3489 g. Urinary incontinence rate at 6 months was 26%. Vaginal delivery was
      associated with a higher incidence of urinary incontinence (relative risk, 2.8)
      compared with cesarean. Forceps delivery increased the risk of urinary
      incontinence (relative risk, 1.5) compared with spontaneous vaginal delivery.
      There was no significant difference between cesareans done before and during
      labor. None of the obstetric risk factors were independently significant.
      CONCLUSION: Cesarean delivery at any stage of labor reduces postpartum urinary
      incontinence. With multivariable analysis, obstetric risk factors are not
      significant.

PMID- 11239636
TI  - Human papillomavirus DNA detection in sperm using polymerase chain reaction.
AB  - OBJECTIVE: To detect human papillomavirus (HPV) in semen and find if sperm
      washing removes HPV DNA. METHODS: Amplification by nested polymerase chain
      reaction (PCR) was used to detect viral DNA sequences in semen samples from 85
      volunteers. Forty-five men had historical or clinical evidence of genital HPV
      infection (study group) and 40 were healthy, clinically HPV-negative semen
      donors. RESULTS: We detected HPV DNA in the sperm cells of 24 of 45 subjects
      (53%) with past or current HPV infections in contrast to three of 40 healthy
      subjects (8%) (P <.001). Overall, PCR detected HPV in 21 of 32 subjects (66%)
      with identifiable lesions and six of 53 (11%) without them (P <.001). Swim-up
      washings of all 27 prewash sperm cells with HPV reduced cellular HPV DNA below
      detectable levels in only two cases. CONCLUSION: HPV is present in sperm cells
      from infected and apparently healthy subjects, and sperm washing does not
      eliminate the risk of HPV transmission to recipients. We suggest that HPV DNA
      testing should be done on the semen of prospective donors, and those with
      positive tests should be excluded from donation.

PMID- 11239637
TI  - Blood pressure in late pregnancy and work outside the home.
AB  - OBJECTIVE: To assess maternal blood pressure (BP) responses to working outside
      the home in late pregnancy, using 24-hour ambulatory BP monitoring. METHODS: Our
      paired observational study involved 24-hour ambulatory BP monitoring of 100
      normotensive women (51 primiparas, 49 multiparas) on work and nonwork days. Mean
      BP differences were calculated for working, postworking, sleeping, and 24-hour
      periods on both days. Main outcome measures were BP differences between work and
      nonwork days and subsequent pregnancy hypertension. Comparisons in BP between
      work and nonwork days were done with Student paired t test. Comparisons between
      study subgroups were done with unpaired t test. Potential predictors of change in
      BP were examined using multiple linear regression. RESULTS: During job time, BP
      was significantly higher on work days than on nonwork days. The mean increase in
      BP associated with work was 2.6 mmHg (systolic BP, P <.001), 2.8 mmHg (diastolic
      BP, P <.001), and 2.9 mmHg (mean arterial BP, P <.001). Those observations were
      independent of parity. More than 10% of our subjects had increased mean arterial
      BP of 10 mmHg or more during job time on work days compared with nonwork days.
      Higher absolute BP levels (regression coefficient 0.21, P =.04) and greater
      perceived job stress (regression coefficient 1.34, P =.04) correlated positively
      with BP increases at work. Twelve women developed hypertension. Those women had a
      larger increase on work days in mean systolic (6.6 mmHg compared with 2.1 mmHg, P
      =.013), mean diastolic (6.4 mmHg compared with 2.3 mmHg, P =.014), and mean
      arterial (7.4 mmHg compared with 2.3 mmHg, P =.002) BP compared with normotensive
      women. The magnitude of BP responses to work was a significant predictor of
      pregnancy hypertension, independent of absolute BP level. CONCLUSION: Blood
      pressure increased in women when they worked outside the home. The effect of
      maternal work is important when treating pregnancy hypertension. Ambulatory BP
      monitoring makes assessment of maternal BP responses to work a practical clinical
      option.

PMID- 11239638
TI  - Plasma adenosine levels and P-selectin expression on platelets in preeclampsia.
AB  - OBJECTIVE: To measure the correlation of plasma adenosine levels with platelet
      activation in women with preeclampsia. METHODS: Plasma adenosine concentration
      and expression of P-selectin, a marker for platelet activation, were measured in
      18 normal pregnant women and 18 preeclamptic women. The effect of 8
      sulfophenyltheophylline, an adenosine receptor blocker, on expression of P
      selectin on platelets also was measured. RESULTS: Plasma adenosine level averaged
      0.77 +/- 0.11 microM (standard error of the mean [SEM]) in women with
      preeclampsia, significantly higher than the mean level of 0.47 +/- 0.08 microM in
      women with normal pregnancies (P <.05). Expression of P-selectin on platelets
      averaged 7.8 +/- 1.2% in women with preeclampsia, also significantly higher than
      the mean level of 4.7 +/- 0.7% in normal pregnancy (P <.05). Adenosine receptor
      blockade significantly increased expression of P-selectin on platelets in women
      with preeclampsia by 26% (P <.05), which was significantly higher than the 13%
      increase of activation in those with normal pregnancies (P <.05). CONCLUSION:
      Adenosine is an established platelet activation suppressor. Increased plasma
      levels of adenosine in preeclampsia might partially compensate and tend to
      prevent further excessive platelet activation in women with preeclampsia.

PMID- 11239639
TI  - Increased systemic activation of neutrophils but not complement in preeclampsia.
AB  - OBJECTIVE: To investigate whether neutrophils and systemic complement are
      activated in pregnancies complicated by preeclampsia more than in normal
      pregnancies. METHODS: We measured native complement components and activation
      products in plasma by enzyme immunoassays in 19 women with uncomplicated
      pregnancies, 15 with preeclampsia before cesarean deliveries, and 16 nonpregnant
      women. Neutrophil activation was measured by specific enzyme immunoassays for
      myeloperoxidase and lactoferrin. RESULTS: Myeloperoxidase was significantly
      higher in women with preeclampsia (197 microg/L, 95% confidence interval [CI] 94,
      646) than in women with uncomplicated pregnancies (124 microg/L, 95% CI 70, 289;
      P =.009), whereas lactoferrin did not differ between groups. C4 was decreased in
      preeclamptic women (0.16 g/L, 95% CI 0.07, 0.48) compared with women with
      uncomplicated pregnancies (0.21, 95% CI 0.10, 0.30, P <.001). There were no
      differences for the other native complement components. There was a significant
      decrease in C1rs-C1 inhibitor, 13 AU/mL (95% CI 9, 34) versus 19 (95% CI 13, 38)
      (P < or =.001) in normal pregnant women compared with nonpregnant women. There
      also was an increase in C3, C4, C9 (data not shown), C4bp, 132% (95% CI 94%,
      161%) versus 91% (95% CI 57%, 128%); C3bc (7.4 AU/mL, 95% CI 4.2, 10.7) versus
      4.8 AU/mL (95% CI 3.2, 7.3) and C4bc (8.6 AU/mL, 95% CI 5.7, 14.0) versus 3.5
      AU/mL (95% CI 2.2, 6.7) in normal pregnant women compared with nonpregnant women
      (P < or =.001). CONCLUSION: Neutrophil activation in preeclampsia was shown by
      systemic increases in myeloperoxidase. Except for a decrease in C4, systemic
      complement activation could not be detected in preeclampsia.

PMID- 11239640
TI  - Balloon cervical ripening with extra-amniotic infusion of saline or prostaglandin
      E2: a double-blind, randomized controlled study.
AB  - OBJECTIVE: To compare extra-amniotic infusion of diluted prostaglandin (PG) E2
      solution with saline infusion in balloon cervical ripening and labor induction.
      METHODS: Women with pregnancy complications and Bishop scores of 3 or lower (n =
      116) were assigned randomly to receive extra-amniotic infusion (1 mL/minute) of
      normal saline or PGE2 in saline (0.5 microg/mL) through a Foley catheter with a
      30-mL inflated balloon. We induced labor using intravenous oxytocin only when
      labor had not developed by 6 hours after balloon expulsion. Analysis was by
      intent-to-treat. We assessed ripening efficiency and course of labor in women who
      had spontaneous balloon expulsion (n = 110) and trial of labor (n = 107),
      respectively. RESULTS: Ripening with PGE2 was associated with significantly
      shorter mean (+/- standard error of the mean [SEM]) time for balloon expulsion
      (4.7 +/- 0.4 versus 6.5 +/- 0.6 hours) and with significantly higher Bishop
      scores (P <.002), compared with ripening with saline. In the PGE2 group, rates of
      labor induction (15%) and oxytocin use (37%) were significantly lower than in the
      saline group (51% and 72%, respectively). The groups did not differ significantly
      in other labor abnormalities, labor duration, mode of delivery, birth weight,
      Apgar scores, and puerperal morbidity. CONCLUSION: Cervical ripening by extra
      amniotic balloon and PGE2 infusion is faster and more effective than by balloon
      and saline infusion, resulting in a higher rate of spontaneous labor and a lower
      rate of oxytocin use.

PMID- 11239641
TI  - Oxytocin dose and the risk of uterine rupture in trial of labor after cesarean.
AB  - OBJECTIVE: To examine the association between uterine rupture and oxytocin use in
      trial of labor after cesarean. METHODS: A case-control study was performed. Cases
      were all women with uterine ruptures who received oxytocin during a trial of
      labor after a single cesarean delivery within a 12-year period (n = 24). Four
      controls undergoing trial of labor after a single cesarean delivery were matched
      to each case by 500 g birth weight category, year of birth, and by induction or
      augmentation (n = 96). The study had an 80% power to detect a 40% increase in
      oxytocin duration or a 65% increase in total oxytocin dose. RESULTS: No
      significant differences were seen in initial oxytocin dose, maximum dose, or time
      to maximum dose. Although women with uterine ruptures had higher exposure to
      oxytocin as measured by mean total oxytocin dose (544 mU higher) and oxytocin
      duration (54 minutes longer), these differences were not statistically
      significant. Women with uterine rupture who received oxytocin were more likely to
      have experienced an episode of uterine hyperstimulation (37.5% compared with
      20.8%, P =.05). However, the positive predictive value of hyperstimulation for
      uterine rupture was only 2.8%. CONCLUSION: Although no significant differences in
      exposure to oxytocin were detected between cases of uterine rupture and controls,
      the rarity of uterine rupture limited our power to detect small differences in
      exposure. In women receiving oxytocin, uterine rupture is associated with an
      increase in uterine hyperstimulation, but the clinical value of hyperstimulation
      for predicting uterine rupture is limited.

PMID- 11239642
TI  - Variation in vaginal breech delivery rates by hospital type.
AB  - OBJECTIVE: To relate vaginal breech delivery rates to the following hospital
      types: public, health maintenance organization, private teaching, or private
      nonteaching. METHODS: In a retrospective study using administrative discharge
      data from Los Angeles County, California, we calculated the vaginal breech
      delivery rates of singleton breech deliveries during calendar years 1988 and
      1991. RESULTS: Ten thousand four hundred breech deliveries were identified, 8988
      (86.4%) term and 1412 (13.6%) preterm. Twelve percent (1252 of 10,400) were
      vaginal deliveries (10.1% term and 24.5% preterm). Term vaginal breech deliveries
      varied by hospital type and were more frequent in public hospitals (28.4%, 95%
      confidence interval [CI] 26.1%, 30.7%) and less frequent in private nonteaching
      hospitals (5.4%, 95% CI 4.8%, 5.9%). Term vaginal deliveries were 2.4 to 11.3
      times more likely among black women and 1.3 to 6.3 times more likely for Hispanic
      women across all hospital types, compared with white women in private nonteaching
      hospitals. There was no difference in the proportion of preterm vaginal breech
      deliveries by hospital type (mean 24.5%). However, with the exception of public
      hospitals, the proportion of vaginal breech deliveries for both term and preterm
      deliveries varied significantly by ethnicity. CONCLUSION: The use of vaginal
      breech delivery varied by hospital type and patient ethnicity. Within private
      teaching and nonteaching hospitals, vaginal breech delivery was more likely for
      black women than for women of other ethnic groups. Further study is needed to
      understand the hospital policies or organizational factors, as well as the
      patient-related sociocultural and clinical factors, that contribute to those
      differences.

PMID- 11239643
TI  - Trial of labor after 40 weeks' gestation in women with prior cesarean.
AB  - OBJECTIVE: To compare outcomes in women with prior cesareans delivering at or
      before 40 weeks' gestation with those delivering after 40 weeks. METHODS: We
      reviewed labor outcomes over 12 years at one institution for women with one prior
      cesarean and no other deliveries who had a trial of labor at term. We analyzed
      the rates of symptomatic uterine rupture and cesarean for term deliveries before
      or after 40 weeks and stratified for spontaneous and induced labor. Potential
      confounding by birth weight was controlled using logistic regression. Adjusted
      odds ratios (OR) and 95% confidence intervals (CI) were calculated. RESULTS: Of
      2775 women with one prior scar and no other deliveries, 1504 delivered at or
      before 40 weeks and 1271 delivered after 40 weeks. For spontaneous labor, rupture
      rate at or before 40 weeks was 0.5% compared with 1.0% after 40 weeks (P =.2,
      adjusted OR 2.1, CI 0.7, 5.7). For induced labor, uterine rupture rates were 2.1%
      at or before 40 weeks and 2.6% after 40 weeks (P =.7, adjusted OR 1.1, CI 0.4,
      3.4). For spontaneous labor, rate of cesareans during subsequent trials of labor
      at or before 40 weeks was 25% compared with 33.5% after 40 weeks (P =.001,
      adjusted OR 1.5, CI 1.2, 1.8). For induced labor, rate of cesareans during
      subsequent trials of labor at or before 40 weeks was 33.8% compared with 43%
      after 40 weeks (P =.03, adjusted OR 1.5, CI 1.1, 2.2). CONCLUSION: The risk of
      uterine rupture does not increase substantially after 40 weeks but is increased
      with induction of labor regardless of gestational age. Because spontaneous labor
      after 40 weeks is associated with a cesarean rate similar to that following
      induced labor before 40 weeks, awaiting spontaneous labor after 40 weeks does not
      decrease the likelihood of successful vaginal delivery.

PMID- 11239644
TI  - Clearance of antiphospholipid antibodies in pregnancies treated with heparin.
AB  - OBJECTIVE: To describe the natural history of serum antiphospholipid antibodies
      (lupus anticoagulant and anticardiolipin antibodies) in pregnant women treated
      with heparin, and to identify a possible association between changes in antibody
      status and outcomes of subsequent pregnancies. METHODS: Thirty-six women with
      antiphospholipid antibodies who had three or more repeated miscarriages were
      enrolled. Intravenous heparin was used for each of the first pregnancies after
      referral. Changes in antibody status were investigated with relation to outcomes
      of the index and subsequent pregnancies. RESULTS: Eighteen of 23 pregnancies in
      36 antibody-positive women treated with heparin resulted in term or preterm
      deliveries with live-born infants, and five ended in abortions. Antibodies
      cleared in ten of 12 term pregnancies, in five of six preterm pregnancies, and in
      one of five abortions. There was a statistically significant difference between
      the term pregnancy and abortion groups (P <.05). Eleven second and third
      pregnancies in nine women in whom antibodies cleared resulted in term or preterm
      deliveries of live-born infants, without heparin therapy. The second and third
      pregnancies in one woman whose antibodies persisted ended in miscarriages despite
      repeated heparin administration. CONCLUSION: Antiphospholipid antibodies cleared
      spontaneously in some pregnant women treated with heparin. Subsequent pregnancies
      among women in whom antibodies cleared were managed successfully without
      medication, whereas pregnancies in women with persistent antibodies required
      treatment.

PMID- 11239645
TI  - Cervical stroma apoptosis in pregnancy.
AB  - OBJECTIVE: To determine whether the percentage of apoptotic nuclei is different
      in cervical stroma of pregnant laboring women compared with nonpregnant women and
      pregnant nonlaboring women. METHODS: We took cervical stromal biopsies during
      cesarean delivery at the level of the lower uterine segment from ten women in
      active labor and 13 women before labor. In addition, we took biopsies of cervical
      stroma at the level of the internal cervical os from hysterectomy specimens in
      ten reproductive-aged women. Cryosections were then analyzed using terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling
      staining. Tissue specimens were analyzed with ligation-mediated polymerase chain
      reaction to visualize nucleosomal ladders characteristic of apoptosis. To detect
      a 10% difference in the percentage of apoptotic cells per subject between study
      groups assuming a power of 0.90, an alpha of.05 in approximately ten subjects per
      group was needed. RESULTS: The median percentage of apoptotic nuclei was 0.7
      (interquartile range 0.4, 1.4) for the nonpregnant group, 7.5 (interquartile
      range 6.6, 11.2) for the pregnant nonlaboring group, and 11.6 (interquartile
      range 8.3, 16.7) for the pregnant laboring group (P <.001). The percentage of
      apoptotic nuclei differed significantly across the three study groups. Using
      ligation-mediated polymerase chain reaction, nucleosomal ladders were seen in the
      specimens from pregnant women but not in the specimens from nonpregnant women,
      confirming the increase in stromal apoptosis seen with pregnancy. CONCLUSION:
      Apoptosis of cervical stromal cells may play a role in the remodeling of the
      cervix during pregnancy and contribute to cervical changes during labor.

PMID- 11239646
TI  - Plasminogen activator system in serum and amniotic fluid of euploid and aneuploid
      pregnancies.
AB  - OBJECTIVE: To compare euploid and aneuploid pregnancies with respect to maternal
      serum and amniotic fluid (AF) levels of the components of the plasminogen system.
      METHODS: The study population consisted of 123 single pregnancies at the 17th
      gestational week, 16 with minor chromosomal abnormalities, 15 aneuploid, and 92
      euploid. RESULTS: Both groups with chromosomal abnormalities had significantly
      higher serum levels of urokinase plasminogen activator and its complexed form
      with its type-1 inhibitor compared with euploid pregnancies. In AF, tissue
      plasminogen activator was significantly lower in the aneuploid than the euploid
      group, whereas type-1 inhibitor of plasminogen activator was significantly higher
      in the cases with minor chromosomal abnormalities compared with euploid. At
      cutoff levels set at 100% sensitivity, the complexed form of urokinase
      plasminogen activator with its type-1 inhibitor had the strongest specificity
      (66.3%); after logarithmic transformation, its serum level was 7.53 times higher
      in aneuploidies than euploidies. CONCLUSION: Aneuploid pregnancies appear to be
      accompanied by abnormalities of the plasminogen activation system, which could
      lead to impaired placental perfusion and thus to abortion, fetal death, and fetal
      growth restriction.

PMID- 11239647
TI  - Prognostic value of DNA quantification in early epithelial ovarian carcinoma.
AB  - OBJECTIVE: To evaluate the prognostic value of flow cytometric DNA quantification
      and immunohistochemical expression of c-erbB-2 and p53, and traditional
      clinicopathologic variables in stages I-II invasive epithelial ovarian cancer.
      METHODS: We retrospectively reviewed 77 cases of stages I-II ovarian cancer after
      comprehensive surgical staging. We recorded anthropometric data (age, menopausal
      status, weight loss, Karnofsky index) and pathologic variables (tumor size,
      bilaterality, capsular status, ascites, peritoneal cytology, histologic type, and
      grade). In 72 cases representative paraffin-embedded samples were available for
      DNA quantification and immunohistochemical evaluation of c-erbB-2 and p53
      overexpression. Most women (87%) had received cisplatin-based adjuvant
      chemotherapy. RESULTS: The median follow-up was 90 months (range 50-148 months).
      The 6-year overall disease-free survival rate was 70% (95% confidence interval
      [CI] 60%, 81%), and overall global survival was 77% (95% CI 67%, 87%).
      Multivariable analysis using Cox stepwise regression identified DNA content (odds
      ratio [OR] 12.3; P <.001) and stage (OR 1.4, P =.09) as independent poor
      prognosis factors for relapse, and DNA content (OR 9.8, P <.001) as the main
      independent factor for survival. In stepwise discriminant analysis the
      combination of DNA content and stage provided a correct prediction of relapse in
      78% of women. CONCLUSION: Flow cytometric DNA quantification was the main
      independent prognostic factor of relapse and survival in these women with stages
      I-II epithelial ovarian cancer.

PMID- 11239648
TI  - Favorable survival associated with microsatellite instability in endometrioid
      endometrial cancers.
AB  - OBJECTIVE: To determine whether microsatellite instability in endometrioid
      endometrial cancer is associated with favorable survival. METHODS: Microsatellite
      instability analysis was performed in 131 patients with endometrioid endometrial
      cancer using three polymorphic markers in paired cancer and normal DNA. Logistic
      regression and multivariable analyses calculated the relation between
      microsatellite instability, clinical features, and survival. RESULTS:
      Microsatellite instability was detected in 29 of 131 (22%) endometrioid
      endometrial cancers. There was no correlation between microsatellite instability
      and age, race, grade, stage, or depth of myometrial invasion. Microsatellite
      instability was associated with better survival in univariate and multivariable
      analyses after controlling for confounding influences (P =.03). The 5-year
      survival rate of those with microsatellite instability was 77% (95% confidence
      interval 55%, 90%) compared with only 48% (95% confidence interval 39%, 57%) in
      other cases. Microsatellite instability was associated with other molecular
      features that predict favorable outcome including PTEN mutation (P =.002) and the
      absence of p53 overexpression (P =.01). CONCLUSION: Microsatellite instability is
      a molecular alteration associated with favorable outcome in endometrioid
      endometrial cancers, even when accounting for other prognostic factors. This
      association might be explained by the finding that the pathway of molecular
      carcinogenesis characterized by loss of DNA mismatch repair favors alteration of
      genes that result in a less virulent clinical phenotype.

PMID- 11239649
TI  - Aspirin effects on endometrial cancer cell growth.
AB  - OBJECTIVE: To find whether aspirin (acetylsalicylic acid, ASA) inhibits the
      growth of endometrial cancer cells in vitro in a way similar to that in
      colorectal cancer cells and to investigate the mechanisms by which aspirin might
      lead to growth inhibition. METHODS: Ishikawa human endometrial tumor cells were
      grown in the presence of ASA (1-5 mM) for 96 hours. Controls were treated with
      vehicle (absolute ethanol). Cell proliferation was assessed by 3-(4,5
      dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide assay. Apoptosis was
      determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end
      labeling assay. Analysis of cell-cycle distribution and bcl-2 expression was
      assessed by flow cytometry. RESULTS: Acetylsalicylic acid induced a dose
      dependent inhibition of Ishikawa cells in vitro. The percentage of growth
      inhibition was 21-88% at concentrations of 1-5 mM. It also induced apoptosis and
      reduced bcl-2 expression in Ishikawa cells in a dose-dependent manner. Control
      cells and cells treated with the lowest concentration of ASA exhibited 2%
      apoptosis and more than 60% of the population expressed bcl-2. Apoptosis levels
      increased as levels of ASA increased from 2 to 5 mM (7-58%) with a concommitant
      decrease in bcl-2 expression from 46% at 2 mM to 2% at 5 mM. Acetylsalicylic acid
      concentrations of 3 mM or greater induced a shift from the resting phase (G0/G1)
      to S phase of the cell cycle. CONCLUSION: Acetylsalicylic acid inhibited Ishikawa
      cell growth in vitro in a dose-dependent manner. Apoptosis is one of the
      mechanisms involved in the response, which can be mediated in part by
      downregulation of bcl-2.

PMID- 11239651
TI  - Adjuvant hysterectomy in low-risk gestational trophoblastic disease.
AB  - OBJECTIVE: To evaluate the efficacy of adjuvant hysterectomy with chemotherapy
      for women with low-risk gestational trophoblastic disease. METHODS: One hundred
      fifteen consecutive Japanese women (16-52 years old) with low-risk gestational
      trophoblastic disease (46 with metastatic disease and 69 without) were treated
      initially with single-agent chemotherapy (etoposide in 85, methotrexate in 27,
      and actinomycin D in three) with or without adjuvant hysterectomy, and 97
      patients (84.3%) achieved primary remission with those treatments. Eight women
      (9.4%) treated with etoposide required other regimens because of drug resistance
      or toxicities. The total dose of etoposide given to achieve primary remission was
      analyzed in 77 women who received etoposide alone or with adjuvant hysterectomy.
      RESULTS: In 34 women with metastatic disease, the mean (+/- standard deviation
      [SD]) total dose of etoposide was not significantly different with and without
      adjuvant hysterectomy (2857 +/- 842 mg versus 2815 +/- 815 mg; P =.957; Mann
      Whitney U test). However, in 43 women without metastases, the total dose of
      etoposide was significantly less in those who had adjuvant hysterectomies than in
      those who did not (1750 +/- 635 mg versus 2545 +/- 938 mg; P <.05; Mann-Whitney U
      test). CONCLUSION: Adjuvant hysterectomy decreased the total dose of etoposide
      given to achieve primary remission in women with nonmetastatic, low-risk
      gestational trophoblastic disease. If the lesions of gestational trophoblastic
      disease are confined to the uterus and the woman has no desire to preserve
      fertility, she should be informed of adjuvant hysterectomy as a treatment option.

PMID- 11239650
TI  - Cervical intraepithelial neoplasia III: long-term outcome after cold-knife
      conization with clear margins.
AB  - OBJECTIVE: To evaluate the long-term outcome of patients with severe cervical
      intraepithelial neoplasia or squamous cell carcinoma in situ (CIN III) after cold
      knife conization with clear margins. METHODS: A total of 4417 women (mean age 36,
      range 18-72 years) with histologically confirmed CIN III had cold-knife
      conization with clear margins at our institution between 1970 and 1994. All
      patients were followed up with colposcopy, cytology, and pelvic examination for a
      mean of 18 years (range 5-30years). RESULTS: New high-grade squamous
      intraepithelial lesions (SILs) (CIN II and III) developed in 15 (0.35%) patients
      (mean age 35, range 25-65 years) after a median of 107 (range 40-201) months. A
      total of 4402 (99.65%) patients (mean age 36, range 18-72 years) were free of
      high-grade SILs after a mean follow-up of 18 (range 5-30) years. High-grade
      glandular intraepithelial lesions developed in two (0.05%) patients 14 and 17
      years after conization. Twelve (0.3%) patients had metachronous vulvar
      intraepithelial neoplasia (VIN) grade III or vaginal intraepithelial neoplasia
      (VAIN) grade III, and one (0.02%) patient had invasive vaginal carcinoma 10 years
      after conization. CONCLUSION: Cold-knife conization with clear margins was an
      adequate method to definitively treat CIN III.

PMID- 11239652
TI  - Randomized double-masked comparison of radially expanding access device and
      conventional cutting tip trocar in laparoscopy.
AB  - OBJECTIVE: To compare postoperative wound pain associated with the radially
      expanding access device and the conventional disposable cutting-tip trocar.
      METHODS: Our randomized, double-masked, self-controlled study involved 34 women
      scheduled for laparoscopic adnexal surgery. In each, a 10-mm radially expanding
      access device was inserted laterally on one side of the lower abdomen and a size
      matched disposable cutting-tip trocar was placed on the other side, using random
      assignment. Postoperative pain for each studied wound and patient satisfaction
      toward the wounds were assessed using a visual analog scale. Any bleeding
      complication associated with insertion of the trocar was also recorded. RESULTS:
      The radially expanding access device was associated with significant reduction in
      severity (median 1.4 versus 5.0, P <.001) and duration (median 11 versus 21 days,
      P <.001) of postoperative wound pain, shorter wound scars (14 versus 17 mm, P
      <.001), a lower incidence of wound induration (0 versus 9, P <.01), and a higher
      patient satisfaction (median 9.7 versus 6.2, P <.001). There were four inferior
      epigastric artery injuries, all at the conventional trocar wound. CONCLUSION: The
      radially expanding access device was associated with less postoperative wound
      pain and more patient satisfaction than the conventional cutting-tip trocar.

PMID- 11239654
TI  - Prenatal diagnosis of congenital cytomegalovirus infection.
AB  - OBJECTIVE: To assess prospectively the diagnostic reliability and prognostic
      significance of prenatal diagnosis of cytomegalovirus (CMV) infection. METHODS:
      One hundred ten pregnant women (four with twin pregnancies) with a risk of
      congenital CMV infection were investigated. Prenatal diagnosis was carried out by
      amniocentesis and fetal blood sampling (n = 75) or amniocentesis alone (n = 35).
      Serial ultrasonographic examinations were performed from time of referral until
      pregnancy end. All infected neonates were given long-term follow-up. Autopsy was
      performed in all cases of termination of pregnancy. RESULTS: Nearly 23% (26 of
      114) of fetuses were infected and prenatal diagnosis was positive in 20 cases.
      Sensitivity of prenatal diagnosis was 77% and specificity 100%. In eight cases,
      parents requested termination of pregnancy on the basis of abnormal
      ultrasonographic findings and/or biologic abnormalities in fetal blood. In 12
      cases, parents decided to proceed with the pregnancy. In this group, one
      intrauterine and one neonatal death were observed. In one case, prenatal
      diagnosis revealed an abnormal cerebral sonography and the infant had bilateral
      hearing loss at birth. In 15 cases (nine positive and six false-negative prenatal
      diagnoses), no apparent lesion was present at birth, nor did it develop during
      the follow-up period (mean 31 months). In 88 (77.2%) of 114 infants, no evidence
      of vertical transmission was found during the pre- or postnatal period.
      CONCLUSION: Prenatal diagnosis provides the optimal means for both diagnosing
      fetal infection (amniocentesis) and identifying fetuses at risk of severe
      sequelae (ultrasound examination, fetal blood sampling), thus allowing proper
      counseling.

PMID- 11239653
TI  - Mode of delivery and risk of respiratory diseases in newborns.
AB  - OBJECTIVE: To determine whether there is an increased incidence of persistent
      pulmonary hypertension in neonates delivered by cesarean, with or without labor,
      compared with those delivered vaginally. METHODS: We did a computerized
      retrospective review of 29,669 consecutive deliveries over 7 years (1992-1999).
      The incidences of persistent pulmonary hypertension of the newborn, transient
      tachypnea of the newborn, and respiratory distress syndrome (RDS) were tabulated
      for each delivery mode. Cases of persistent pulmonary hypertension were reviewed
      individually to determine delivery method and whether labor had occurred. The
      three groups defined were all cesarean deliveries, all elective cesareans, and
      all vaginal deliveries. RESULTS: Among 4301 cesareans done, 17 neonates had
      persistent pulmonary hypertension (four per 1000 live births). Among 1889
      elective cesarean deliveries, seven neonates had persistent pulmonary
      hypertension (3.7 per 1000 live births). Among 21,017 vaginal deliveries, 17
      neonates had persistent pulmonary hypertension (0.8 per 1000 live births). chi2
      analysis showed an odds ratio 4.6 and P <.001 for comparison of elective cesarean
      and vaginal delivery for that outcome. CONCLUSION: The incidence of persistent
      pulmonary hypertension of the newborn was approximately 0.37% among neonates
      delivered by elective cesarean, almost fivefold higher than those delivered
      vaginally. The findings have implications for informed consent before cesarean
      and increased surveillance of neonates after cesarean.

PMID- 11239655
TI  - Intrauterine blood flow and long-term intellectual, neurologic, and social
      development.
AB  - OBJECTIVE: To study the long-term effects of severely abnormal (absent or
      reversed diastolic) blood flow in the umbilical artery associated with fetal
      growth restriction on postnatal intellectual, neurologic, and social development.
      METHODS: Absence or reversal of diastolic blood flow in the umbilical artery was
      found in 38 consecutive growth-restricted fetuses as determined by biometry and
      Doppler ultrasound between 1988 and 1992. The 23 infants surviving the prenatal
      and perinatal period who could be tested were compared at school age with a group
      of children born at the same gestational age after normal intrauterine growth.
      They were tested for intellectual, neurologic, and social development by a test
      battery including the Kaufmann Assessment Battery for Children, Man-Drawing Test,
      Child Behavior Checklist, Zurich Neuromotor Test, and neuropediatric testing.
      RESULTS: Intellectual development was significantly better in the control group
      compared with the study group. In addition, Zurich Neuromotor testing and
      neuropediatric testing showed significantly better development of control
      children compared with the study group in 20% of the items tested. There was no
      detectable difference in social development as measured by the Child Behavior
      Checklist. CONCLUSION: Severely reduced blood flow to the fetus associated with
      growth restriction was followed by long-term impairment of intellectual
      development and partial neurodevelopmental delay.

PMID- 11239656
TI  - Fetal heart rate overshoot during repeated umbilical cord occlusion in sheep.
AB  - OBJECTIVE: To assess the clinical utility of overshoot fetal heart rate (FHR)
      decelerations by examining their occurrence after umbilical cord occlusions of
      varying frequency and length in near-term fetal sheep. METHODS: Fetuses were
      allocated to the following three groups: 1-minute umbilical cord occlusion
      repeated every 5 minutes (1:5 group, n = 8) or every 2.5 minutes (1:2.5 group, n
      = 8) or 2-minute occlusions repeated every 5 minutes (2:5 group, n = 4).
      Occlusions were continued for 4 hours or until fetal mean arterial pressure
      decreased below 20 mmHg during two successive occlusions. RESULTS: In the 1:5
      group, fetuses tolerated 4 hours of occlusion without hypotension or clinically
      significant acidosis and overshoot never occurred. In the 2:5 group, fetuses
      rapidly became hypotensive and acidotic, and occlusions were terminated at 116.3
      +/- 22.9 min (mean +/- standard deviation). Overshoot was seen after every
      occlusion, starting with the first occlusion. In the 1:2.5 group, fetuses became
      progressively acidotic and hypotensive and occlusions were stopped at 183.1 +/-
      42.8 min. Overshoot occurred after 91.6 +/- 42.5 minutes, at a pH of 7.17 +/-
      0.06, base deficit 9.3 +/- 4.5 mmol/L. After the appearance of overshoot there
      was a more rapid decrease in fetal mean arterial pressure (0.25 [0.21, 0.35, 25
      75th percentile] mmHg/minute versus 0.11 [0.03, 0.15] mmHg/minute before
      overshoot appeared, P <.01). CONCLUSION: These data suggest that overshoot is
      related to longer (2-minute) occlusions or to developing fetal acidosis and
      hypotension during 1-minute occlusions. This pattern could have clinical utility,
      as 1-minute contractions are typical of active labor.

PMID- 11239657
TI  - Fetal DNA in maternal circulation of first-trimester spontaneous abortions.
AB  - OBJECTIVE: To establish whether fetal DNA can be identified in the maternal
      circulation in first-trimester spontaneous abortions. METHODS: Women with
      confirmed spontaneous abortions and no histories of previous pregnancy were
      recruited. Peripheral venous blood samples were obtained and DNA extracted. Real
      time quantitative polymerase chain reaction was done using SRY and beta-actin
      systems for calculating fetal and total DNA, respectively. RESULTS: Of 25 women,
      SRY-specific signals were detected in 11 indicating that the abortions were male.
      The remaining 14 were negative for the SRY gene. Women with positive results were
      of similar gestational age to those who were negative (mean 68.4 and 69.0 days).
      Fetal:total DNA ratio was calculated for positive samples and ranged from 15.8 to
      360.1 x 10(+3). Mean ratio was 99.4 x 10(+3) and median was 67.5 x 10(+3).
      CONCLUSION: Fetal DNA is present in the maternal circulation of first-trimester
      spontaneous abortions.

PMID- 11239658
TI  - Diagnosing ectopic pregnancy: decision analysis comparing six strategies.
AB  - OBJECTIVE: To compare six published methods of diagnosing ectopic pregnancy.
      METHODS: Decision analysis compared six diagnostic algorithms involving
      combinations of clinical examination, transvaginal ultrasound, serum
      progesterone, serum hCG, and D&C. The population was composed of hemodynamically
      stable women who presented to a tertiary care university emergency department
      with abdominal pain or bleeding in their first trimesters. Outcome measures
      included number of missed ectopic pregnancies, potentially interrupted
      intrauterine pregnancies, surgical and diagnostic procedures, time until
      diagnosis, and cost. RESULTS: Ultrasound followed by serum hCG in women with
      nondiagnostic scans yielded the most favorable outcomes; no ectopic pregnancy was
      missed, only 1% of all potential intrauterine pregnancies were interrupted, and
      time to diagnosis averaged 1.46 days. Quantitative hCG measurement followed by
      ultrasound only in women with hCG levels above the discriminatory zone was
      optimal if sensitivity of ultrasound to diagnose intrauterine pregnancy was less
      than 93%. Serum progesterone measurement was not favored because it was
      associated with missed ectopic pregnancies (2.6%). CONCLUSION: Given the current
      accuracy of tests for diagnosing ectopic pregnancy, algorithms using a
      combination of ultrasound and hCG resulted in the best outcomes. Ultrasound as
      the first step was the most efficient and accurate method of diagnosing ectopic
      pregnancies.

PMID- 11239659
TI  - Digoxin to facilitate late second-trimester abortion: a randomized, masked,
      placebo-controlled trial.
AB  - OBJECTIVE: To examine the efficacy of digoxin for decreasing operative time,
      difficulty, and pain of late second-trimester surgical abortions. METHODS: We
      performed a randomized, double-masked, placebo-controlled trial of intra-amniotic
      digoxin for second-trimester dilation and evacuation (D&E) involving 126
      consecutive women at an inner-city public hospital. Eligible women had
      gestational ages of 20-23.1 weeks, spoke English or Spanish, and were at least 16
      years old. Digoxin (1 mg) or saline was injected intra-amniotically 24 hours
      before the procedure, at cervical laminaria insertion. The primary outcome was
      procedure duration. Sample size was based on 80% power to detect a difference of
      3.5 minutes between groups. RESULTS: The two groups were similar in demographic
      factors, obstetric histories, and gestational duration. The average gestational
      length was 22.5 weeks. There was no difference in procedure duration (mean +/-
      standard deviation) between groups (placebo 14.7 +/- 7.0, digoxin 15.4 +/- 8.0).
      There were no differences in blood loss estimated by surgeons, pain scores,
      procedure difficulty scores, or complications between groups. Vomiting was
      significantly more common in those who received digoxin (placebo 3.1%, digoxin
      16.1%). Most subjects (91%) reported that they preferred their fetuses were dead
      before the abortions. CONCLUSION: Although digoxin did not increase efficacy of
      late second-trimester abortion, patient preference might justify its use.

PMID- 11239660
TI  - Androsterone sulfate increases dentate gyrus population spike amplitude following
      tetanic stimulation.
AB  - We studied the effects of the androgenic hormone, androsterone sulfate, a 17
      ketosteroid, on long term potentiation in the dentate gyrus (DG) of urethane
      anesthesized rats. Intravenous injection of 10 mg of the hormone dissolved in
      Nutralipid produced a significant increase of the population spike (PS), but not
      of the excitatory post-synaptic potentials (EPSP). The results are discussed in
      terms of the potential enhancement that androsterone sulfate may have on memory
      as was described for one of its parent compounds, dehydroepiandrosterone (DHEA)
      and its potential use as an antidepressant.

PMID- 11239661
TI  - Persistent stress-induced elevations of urinary corticosterone in rats.
AB  - Exposure of rats to inescapable stressors (IS) results in persistent elevations
      in plasma corticosterone (CORT), which are selective to the trough of the
      circadian rhythm. Although affective disorders (depression, anxiety) in humans
      are also characterized by persistent hypothalamic-pituitary-adrenal axis (HPAA)
      activation, the predominant measure of HPAA activation in clinical studies is 24
      h urinary cortisol. To facilitate interspecies comparisons regarding the
      persistent effects of stress on HPAA activity, we compared the effects of IS on
      plasma and urinary CORT in rats. Male Sprague-Dawley rats were exposed to three 2
      h sessions of IS (40, 2.0 mA tailshocks) or remained in their home cages. The 24
      h urine samples were collected daily from 2 days prior to stress to 5 days after
      stressor cessation, then weekly for 3 weeks. In addition, plasma samples were
      obtained at 08:00 (trough) and 20:00 hours (peak) for the first 3 days after
      stressor cessation and weekly for 3 weeks thereafter. Consistent with our earlier
      work, plasma CORT elevations were apparent in the trough, but not the peak
      samples for 3 days after stressor cessation. The 24-h urinary CORT levels were
      elevated during stressor exposure, and remained elevated for 3 days after
      stressor cessation. Persistent stress-induced urinary CORT elevations in rats are
      reminiscent of the clinical HPAA abnormalities described for major depression and
      affective disorders.

PMID- 11239662
TI  - Food availability affects behavior but not circulating gonadal hormones in
      maternal Belding's ground squirrels.
AB  - We tested predictions of hypotheses suggesting that the steroid hormones,
      testosterone (T), progesterone (P), and estradiol (E2), contribute to the
      energetic regulation of behaviors associated with rearing young in free-living
      female Belding's ground squirrels (Spermophilus beldingi). We provisioned some
      female S. beldingi with food rich in fat and calories, and used unprovisioned
      females as controls. We observed the behavior of females throughout the
      reproductive cycle, and regularly collected blood samples to measure plasma
      hormone concentrations. Circulating concentrations of T, P, and E2 were similar
      in provisioned and unprovisioned females, as were temporal patterns of variation
      in these hormones. Peaks in rates of nest maintenance and aggressive behavior
      occurred during gestation and were associated with elevated concentrations of
      circulating T, P, and E2, raising the possibility that one or more of these
      hormones mediates behaviors that help females establish maternal nest sites and
      territories after mating. Temporal patterns of variation in behavior were similar
      among provisioned and unprovisioned females; however, rates of resting,
      vigilance, and aggression were higher among provisioned females, whereas
      unprovisioned females devoted significantly more time to feeding and locomotion.
      Thus, our data suggest that in maternal S. beldingi, gonadal steroids play a role
      in mediating behavior associated with raising offspring, but do not facilitate
      changes in rates of behavior associated with increased energy availability.

PMID- 11239663
TI  - Taste preference and acceptance in thirsty and rehydrated [correction of
      dehydrated] rats.
AB  - Experiments were designed to determine whether water deprivation affects taste
      preferences and/or taste acceptance. In experiment 1, both five- and two-bottle
      preference tests were performed in normally hydrated rats to permit the selection
      of five groups of rats showing the same taste preference for one of four
      prototypical tastes. Subsequently, in the same groups of rats, taste preferences
      were determined by a two-bottle test (experiment 2), and taste acceptance by a
      one-bottle test (experiment 3), following 12, 24, 36, and 48 h of water
      deprivation. After both 12 and 24 h of dehydration, during the first 10 min of
      the tests of experiment 2, all rats ingested greater volumes of either NaCl or
      sucrose solution than water, but more water than either HCl or quinine solution,
      and the differences were very significant (P<.0001). After 36 or 48 h of
      dehydration, the differences became very small and, in some cases, the P-values
      were at the lowest or borderline level of the significance, suggesting that
      dehydrated rats poorly discriminate the nature of the fluid drunk. During the 11
      60 min interval, all rats preferred either sucrose or NaCl to water, but water to
      either HCl or quinine. Experiment 3 was performed to ascertain whether the need
      for fluid might overcome the palatability of solutions. All rats, dehydrated for
      36 or 48 h, after 10 min of exposure, drank equal amounts of fluid, independent
      of its palatability. During the 11-20 and 21-60 min interval, the fluid intake of
      rats changed in accordance with the palatability of the solution available. In
      conclusion, severe thirst in rats may override the palatability of the solutions,
      and the thirst drive may be so strong that they do not reject fluids because body
      fluid balance would be severely compromised.

PMID- 11239664
TI  - Relationships between mood states and performances in reaction time, psychomotor
      ability, and mental efficiency during a 31-day gradual decompression in a
      hypobaric chamber from sea level to 8848 m equivalent altitude.
AB  - High altitude is characterized by hypoxic environmental conditions that may
      induce a set of pathological disorders, known as acute mountain sickness. In
      addition to the physiological symptoms, exposure to high altitude may also
      produce adverse changes in motor skills, mental efficiency, and mood states,
      including anxiety. In the present study, we investigated the relationships
      between mood states, including anxiety, and performance changes in reaction time,
      psychomotor ability and mental efficiency in eight climbers participating in the
      'Everest-Comex 97', a 31-day gradual decompression in a hypobaric chamber from
      sea level to 8848 m equivalent altitude. Tests of visual reaction time, manual
      dexterity, and number ordination were used; anxiety responses and mood states
      were assessed using the Spielberger State-Trait Anxiety Inventory (STAI) and the
      'Profile of Mood States' (POMS), respectively. A significant positive correlation
      was found between the climbers' performance in reaction time and changes in state
      type anxiety levels, suggesting that anxiety could lead to an improved reaction
      time. In addition, significant negative correlations were also found between the
      climbers' performance in psychomotor ability, mental efficiency, and reaction
      time, and several POMS factors, including Tension, Hostility, Confusion, and
      Fatigue. Overall, these data indicate, in agreement with previous studies, that
      anxiety may favour, or at least not alter, the processes of information of
      relatively simple tasks, such as reaction time, and further suggest that adverse
      changes in moods could modulate performance negatively.

PMID- 11239665
TI  - Effects of restricted food access on circadian fluctuation of serotonin N
      acetyltransferase activities in hereditary microphthalmic rats.
AB  - The characteristics in diurnal fluctuation of serotonin N-acetyltransferase
      activity were examined in normal and microphthalmic mutant rats of the Donryu
      strain under ad lib or restricted feeding conditions. Under a 12:12-h light:dark
      (12-h LD) cycle with free access to food, normal-sighted rats exhibited typical
      nocturnal increases in the activity of pineal serotonin N-acetyltransferase,
      being more than 50-fold higher in the dark period than that in the light period,
      but hereditary blind rats showed nonperiodic change in the pineal enzyme activity
      in the average, suggesting that the rhythms in individuals have become free
      running, asynchronous. When the subjective night or subjective day of the mutants
      was discerned by active or inactive in the locomotor activity, the pineal enzyme
      activities in the mutants increased at the subjective night but depressed at the
      subjective daytime. When food access was restricted only for 6 h in the light
      period of the LD cycle, normal rats still showed the nocturnal increases in the
      pineal enzyme activity, but hereditary blind rats manifested a blunt peak in the
      activity of the pineal enzyme at eating time in the light period. The results
      suggest that microphthalmic mutant rats maintain the ability to shift and to
      synchronize their circadian phases induced by restricted access to food, even if
      they completely lack their optic nerve and visual input to the circadian clock.

PMID- 11239666
TI  - The impact of music upon sleep tendency as measured by the multiple sleep latency
      test and maintenance of wakefulness test.
AB  - Previous work has shown that background noise or music has a small positive
      impact on performance during sleep deprivation. The current study examined the
      effect of background music on the ability to fall asleep or remain awake. Twelve
      normal-sleeping young adults took multiple sleep latency tests (MSLT) and
      maintenance of wakefulness tests (MWT) after baseline sleep and one night of
      total sleep deprivation either with background music or under standard (quiet)
      conditions. It was hypothesized that the music would help maintain wakefulness
      both under baseline and sleep deprivation conditions. The results of the study
      showed that sleep latencies were increased in both MSLT and MWT when music was
      presented, but that this effect occurred primarily before subjects were sleep
      deprived (a significant Music by Sleep Deprivation interaction). Sleep latencies
      were 15 and 11 min on the MSLT (33 and 26 min on the MWT) with Music as compared
      to Quiet after baseline sleep. Heart rate, used as a measure of physiological
      arousal, was significantly elevated in MWT and MSLT trials where music was
      presented. These data support previous work showing that level of arousal has an
      impact on measured sleep tendency which is independent of that of the sleep
      system. On a practical level, these data indicate that music may play a small
      beneficial role in helping to maintain arousal.

PMID- 11239667
TI  - Photoperiod and gender affect adipose tissue growth and cellularity in juvenile
      Syrian hamsters.
AB  - Adult Syrian hamsters are reproductively active and at their annual body and
      lipid mass nadirs in long 'summer-like' days (LDs), whereas they are
      reproductively quiescent and at their annual body and lipid mass peaks in short
      'winter-like' days (SDs). Because hamsters are born in the SDs of fall in the
      wild, the development of the reproductive system of juvenile Syrian hamsters
      exposed to SDs has been studied in the laboratory, but not the development of
      body and lipid mass. Therefore, we tested the effect of SDs on white adipose
      tissue (WAT) growth and cellularity (fat cell number, FCN; fat cell volume, FCV)
      in 3-15-week-old male and female Syrian hamsters. SDs increased body fat in both
      genders. This effect was partially independent of the decline in gonadal steroids
      because gonadal regression was only beginning in males (Week 11) and females
      (Week 15) when carcass lipid content was significantly increased in males, and
      nearly so in females. This SD-induced increased adiposity was reflected in few
      regional differences in WAT growth, and then only in males (increased mesenteric
      and inguinal WAT masses). SDs increased FCV for all non-gonadal WAT and increased
      FCN only in retroperitoneal WAT. SDs blunted the LD-induced increased FCV and FCN
      of parametrial and epididymal WAT, respectively. For nearly all conditions and
      pads, FCV peaked first, followed by increased FCN, the latter accounting for
      nearly all WAT growth. These data appear to support the view that adipocyte
      proliferation is stimulated once a 'critical' FCV is reached.

PMID- 11239668
TI  - Sexual behavior of Zebu cattle (Bos indicus) following estrous induction by
      Syncro-Mate B, with or without estrogen injection.
AB  - The effect of estrogen administered with norgestomet implants in the expression
      of behavioral estrous of Zebu cattle was studied in a herd of 18 cycling Brahman
      cows, in two trials. In the first and second trials, six different cows were
      treated with progestagen on successive days. In addition, in the first trial,
      estrogen injection was applied with the treatment. With the purpose of enhancing
      mounting behavior in treated and/or non-treated animals, on the third day of each
      trial, three other cows with an active CL were injected with 25 mg of PGF2alpha.
      All animals were examined three times a week by rectal ultrasound, and a blood
      sample was also taken for progesterone analysis. Sexual activity was monitored by
      a closed-circuit TV from 1500 to 0600 h. Direct observation was carried out from
      0900 to 1200 h. A total of 15 cows displayed 36 mounting periods (11 with
      ovulation). Twenty-five annovulatory estrous periods were observed, 77% supported
      by large follicles. More cows (66% vs. 16%) showed mounting activity when
      estradiol valerate was used as part of the progestagen treatment (P=.03).
      Ovulation rate in response to the effect of norgestomet implant was 16%,
      independent of treatment. It is concluded that estrogen administered with
      norgestomet implants increases the expression of behavioral estrous in Bos
      indicus cattle but does not improve ovulation rate.

PMID- 11239669
TI  - Behavioral profile of wild mice in the elevated plus-maze test for anxiety.
AB  - Systematic observations of the defensive behavior of wild rodents have greatly
      informed the experimental study of anxiety and its neural substrates in
      laboratory animals. However, as the former work has been almost exclusively
      carried out in rats, few data are available concerning the reactivity of wild
      mice to standardized tests of anxiety-related behavior. In the present
      experiments, we employed ethological measures to examine the behavioral responses
      of a wild-derived population of house mice (Mus musculus) in the elevated plus
      maze. In direct comparisons with laboratory Swiss mice, male wild mice exhibited
      substantially elevated levels of exploratory activities and an overall
      "preference" for the open arms of the plus-maze. On re-exposure to the plus-maze,
      male wild mice showed further increases in open arm exploration, while Swiss mice
      showed a marked shift to the enclosed parts of the plus-maze. Tested over a
      single session, female wild mice also exhibited a profile of high open arm
      exploration, but showed levels of exploratory behaviors and locomotor activity
      similar to female Swiss counterparts. While exploratory patterns in wild mice
      show similarities to profiles seen in certain laboratory strains (e.g., BALB/c),
      wild mice displayed a number of additional behaviors that are unprecedented in
      plus-maze studies with laboratory mice. These included actual and attempted jumps
      from the maze, spontaneous freezing, and exploration of the upper ledges of the
      closed arms. Thus, while in conventional terms the behavior of wild mice was
      consistent with one of low anxiety-like behavior, the presence of these unique
      elements instead indicates a profile more accurately characterized by high
      reactivity and escape motivation. We discuss how the use of an ethological
      approach to measuring plus-maze behavior can support accurate interpretation of
      other exceptional profiles in this test, such as those possibly arising from
      phenotyping of transgenic and gene knockout mice.

PMID- 11239670
TI  - Divergent levels of anxiety in mice selected for differences in sensitivity to a
      convulsant agent.
AB  - Spontaneous behavior patterns were assessed in eight different behavioral
      situations in two lines of mice, BR and BS, previously selected for their
      sensitivity to an anxiogenic benzodiazepine (BZ) receptor inverse agonist, Methyl
      beta-carboline-3-carboxylate (beta-CCM). BR is highly resistant, and BS, highly
      sensitive to beta-CCM-induced seizures. Tests used included an assessment of
      general locomotor activity, several situations classically used for measuring
      fear-motivated behaviors (open field, thigmotaxis, elevated plus-maze, light-dark
      discrimination, staircase), a test for measuring exploration (holeboard), and a
      test for measuring nociception (hot-plate). In the absence of beta-CCM, the
      results provide evidence of reduced motor activity and higher levels of anxiety
      in the BR line as compared to the BS line.

PMID- 11239671
TI  - Differential basis of strain and rearing effects on open-field behavior in Fawn
      Hooded and Wistar rats.
AB  - Open-field behavior was examined under several conditions in isolation-reared,
      and socially reared, Fawn Hooded (FH) and Wistar rats. Lighting conditions (red
      or white light) and complexity (object or no object) were varied: Experiment 1,
      white light, no object; Experiment 2, red light, no object; Experiment 3, white
      light, object; Experiment 4, red light, object. The plasma corticosterone (CORT)
      response to open-field exposure was examined two further experiments. Observation
      of differences in open-field behavior, resulting from strain or rearing
      condition, was dependent on both lighting condition and complexity. Differences
      in exploratory behavior exhibited by isolation-reared rats were best explained by
      changes in response to novelty, while those in FH, relative to Wistar, rats were
      primarily due to increased anxiety. Supporting these conclusions, FH rats had
      enhanced stimulated CORT levels, while isolation rearing was without effect.

PMID- 11239672
TI  - Basolateral and central amygdaloid lesions leave aversion to dietary amino acid
      imbalance intact.
AB  - Expression of c-fos is increased in the central amygdaloid nucleus (CE) of rats
      ingesting a diet with a severely imbalanced essential amino acid profile (IMB),
      at a time associated with development of a conditioned taste aversion (CTA). The
      CE and the basolateral amygdaloid nucleus (BL) both are reported to be involved
      in the development of CTA. Large amygdaloid lesions involving CE and BL mitigate
      the normal decrease in intake of IMB; this treatment also impairs CTA to a flavor
      cue associated with gastrointestinal discomfort. To differentiate their potential
      roles in aversive responses to IMB, we electrolytically lesioned CE and BL
      separately. Neither lesion attenuated IMB-induced anorexia, or prevented the
      avoidance of flavored solutions previously paired with IMB. In contrast, after
      saccharin-LiCl pairing, CE-lesioned animals showed attenuated CTA to saccharin
      solution in a two-bottle test. We conclude that neither the CE nor the BL is
      essential for the reduction of IMB intake, or for CTA associated with IMB.
      Furthermore, these results suggest that the aversive consequences of IMB intake
      do not involve gastrointestinal malaise-evoked neurotransmission involving the
      CE.

PMID- 11239673
TI  - Effects of prenatal stress on development in mice: maturation and learning.
AB  - Female CD-1 mice were stressed during the final week of gestation. Beginning 3
      days after birth, until weaning, their pups were examined for eye opening,
      startle response, tooth eruption, surface righting, ability to cling to and climb
      an incline, tail pull reflex, rotation, linear movement and exploration. At 3
      months of age, they were tested in a Morris Water Maze. Stressed animals were
      significantly lighter and shorter than non-stressed animals the first week after
      birth. By 3 days after birth, significantly fewer stressed animals could rotate
      or right themselves. By 6 days after birth, significantly fewer stressed animals
      could cling to or climb an inclined screen, or show the tail pull reflex. By 9
      days of age, significantly fewer stressed animals had teeth. In contrast, by day
      12 of age, significantly more stressed animals demonstrated exploratory behavior
      than did non-stressed animals. There were no sex differences in the ability of
      animals to perform these tasks at the same age. Stressed animals were
      significantly slower than non-stressed animals to reach the hidden platform in
      the water maze on all trials, and this difference was due to stressed females
      being slower to find the platform than non-stressed females, with no main effect
      of stress on males. This study supports and expands previous findings in rodents
      that prenatal stress can cause deficiencies in some early indices of physical
      maturation and also that these deficiencies can be continued into adulthood.

PMID- 11239674
TI  - High social anxiety and low aggression in Fawn-Hooded rats.
AB  - The Fawn-Hooded (FH) rat strain, with well-documented changes in their
      serotonergic and noradrenergic systems, is a putative genetic model for some
      neuropsychiatric disorders like depression, alcohol abuse, and anxiety. Because
      social phobia frequently occurs in combination with these disorders and there are
      no social anxiety-related data in FH rats in the literature, we measured the
      behavior of FH rats in the social interaction test. In addition, the effects of
      the anxiogenic Serotonin-2C (5-HT2C) receptor agonist, m-chlorophenylpiperazine
      (m-CPP), were studied. Male FH, Wistar (W), and Sprague-Dawley (SD) rats were
      used in two different test conditions of the social interaction test: the high
      light, unfamiliar arena, associated with high anxiety, and the low light,
      familiar arena, associated with low anxiety-like behavior. All social behaviors
      were markedly diminished in FH rats that suggested higher anxiety in these
      animals. Total social interaction time was reduced by 60-70% in FH rats compared
      either to W or SD rats under high light, unfamiliar or low light, familiar
      conditions, respectively. Aggressive behavior was reduced at least by 85% in FH
      rats. Locomotor activity and exploratory behavior were only minimally, in most
      comparisons, not significantly affected in FH rats. Total social interaction
      time, aggression, and locomotor activity were decreased, and self-grooming
      increased by m-CPP (0.5 mg/kg, ip) in all three strains. m-CPP decreased total
      social interaction time thus, caused anxiety most efficiently in FH rats (reduced
      by 69%, 50%, and 55% in FH, W, and SD rats, respectively), but other effects of
      the drug were similar in the three strains. Our studies provide evidence that the
      FH rat strain may be a genetic model of social phobia or other anxiety disorders
      with impaired social behavior.

PMID- 11239675
TI  - Frustrative nonreward and pituitary-adrenal activity in squirrel monkeys.
AB  - Little is known about frustration-induced changes in stress physiology in humans
      and nonhuman primates. Here we assess in two experiments with squirrel monkeys
      plasma levels of pituitary-adrenal stress hormones in conditions designed to
      provoke frustrative nonreward. In the first experiment 18 prepubertal monkeys
      were trained to feed from one of eight sites, and then tested without food at any
      of the sites. These monkeys responded with significant increases in cortisol and
      adrenocorticotropic hormone (ACTH). In the second experiment 18 adult monkeys
      were trained to feed from one of eight sites, and then tested after food was
      moved to a different foraging site. Nine monkeys found food at the relocated
      site, discontinued foraging at the previously baited site, and responded with
      decreases in cortisol. The other nine monkeys failed to find the relocated site,
      initially increased their visits to the previously baited site, and responded
      with elevations in cortisol and ACTH. In keeping with comparable findings in
      rats, our observations indicate that frustrative nonreward elicits ACTH
      stimulated secretion of cortisol in primates.

PMID- 11239676
TI  - The nicotinic antagonist mecamylamine preferentially inhibits cocaine vs. food
      self-administration in rats.
AB  - Nicotinic acetylcholine systems play important roles in addiction, and nicotinic
      receptor stimulation stimulates dopamine release while the nicotinic antagonist
      mecamylamine reduces it. Reid et al. [Neuropsychopharmacology 20 (1999) 297.]
      recently found in human cocaine addicts that mecamylamine reduced cue-elicited
      cocaine craving. The current study assessed the impact of mecamylamine on cocaine
      self-administration in rats. Female Sprague-Dawley rats (N=7) were implanted with
      intravenous (iv) catheters and trained to lever press for cocaine (0.32
      mg/kg/infusion FR-1 with a 60-s timeout) in 45-min sessions. After 2 weeks of
      training, the rats were injected with saline or mecamylamine (1, 2, or 4 mg/kg
      sc) 10 min before the session. They received the same dose for 1 week with 1 week
      of uninjected testing between doses. Mecamylamine, compared to saline,
      significantly (P<.05) reduced the number of cocaine infusions per session with
      each of these doses. This effect did not appear to be due to a generalized
      reduction in behavioral activity. Another set of female Sprague-Dawley rats (N=8)
      were trained to lever press for food reinforcement. In these rats, the 1 and 2
      mg/kg mecamylamine doses had no effect on food self-administration. Significant
      reductions in food self-administration were not seen unless the high dose of 4
      mg/kg mecamylamine was used. Nicotinic antagonist treatment reduces cocaine self
      administration in rats at doses that do not cause generalized effects on food
      reinforced responding. Nicotinic antagonistic treatment may be a useful new
      approach to treat cocaine addiction.

PMID- 11239677
TI  - Lithium-induced context aversion in rats as a model of anticipatory nausea in
      humans.
AB  - In three experiments, rats received injections of lithium chloride (LiCl) before
      being exposed to a distinctive context. In a subsequent test, rats given access
      to sucrose solution in this context consumed less than control subjects given
      sucrose in another context that had been paired with a saline injection
      (Experiment 1), or was quite novel (Experiment 2). Experiment 3 demonstrated that
      a context that had been associated with LiCl would serve to block the acquisition
      of a conditioned flavor aversion when it was presented immediately after the
      injection on a flavor-LiCl trial. These results show that a procedure in which
      rats experience the adverse effects of a lithium injection in the presence of
      contextual cues is effective in endowing those cues with aversive properties. It
      is argued that the context evokes a state of conditioned nausea, and the parallel
      with the clinical phenomenon of anticipatory nausea and vomiting (ANV) in human
      patients is outlined.

PMID- 11239679
TI  - A GPS logger and software for analysis of homing in pigeons and small mammals.
AB  - A detailed analysis of homing in pigeons and small mammals has remained difficult
      because the paths of the animals could not be reconstructed precisely. Here, we
      describe a lightweight global position system (GPS) data logger (35 g including
      battery and casing; 40 x 68 x 18 mm) that records the flight of pigeons and the
      path of dogs with an accuracy of +/-12 m. With one battery, the logger runs in
      continuous mode (1 fix/s) for 3.5 h and in power-saving mode (1 fix/5 s) for
      about 16 h, and stores a maximum of 100,000 data points that are downloaded to a
      PC. A module of our public domain software WINTRACK permits a detailed numerical
      and graphical analysis of path geometry, phases of resting and moving, and path
      similarity. The device can be adapted to different species provided that
      satellite signals can be received reliably and that the loggers can be recovered.
      We expect it to be useful for testing hypotheses about pigeon homing, assessing
      natural spatial behavior and orientation of many species, and anticipate further
      miniaturization.

PMID- 11239678
TI  - Slow cortical DC-potential responses to sweet and bitter tastes in humans.
AB  - Processing of hedonic stimulus quality is assumed to be accompanied by a tuning
      of cortical arousal and excitability. In this pilot study in 11 healthy humans
      scalp-recorded DC potentials were assessed during application of a sweet
      (sucrose) and bitter (quinine hydrochloride) taste, i.e., primary reinforcers of
      positive and negative quality. Muscular, ocular, and skin potential activity were
      controlled. Application of sucrose induced a widespread positive DC-potential
      shift with an amplitude of 40-50 microV and persisting for more than 120-s post
      stimulus onset. Following administration of quinine hydrochloride, this positive
      shift was reduced, most distinctly between 48- and 88-s post-stimulus onset. The
      reduction appeared to be most consistent at anterior midline recording sites (Fz,
      Cz). It is assumed that the higher DC-potential positivity during sweetness than
      during bitterness points to a differential tuning of cortical excitability by a
      widespread decrease in depolarization of apical dendrites.

PMID- 11239680
TI  - Methyltestosterone pharmacokinetics and oral bioavailability in rainbow trout
      (Oncorhynchus mykiss).
AB  - 14C-methyltestosterone pharmacokinetics after intraarterial (2 and 20 mg/kg) and
      oral (30 mg/kg) administration were investigated in rainbow trout at 15 degrees
      C. Plasma concentrations of methyltestosterone were determined by reverse phase
      high performance liquid chromatography (HPLC) in combination with reverse isotope
      dilution for up to 6 and 12 days after oral and intraarterial administration,
      respectively. Methyltestosterone pharmacokinetic parameter values after
      intraarterial administration were determined using a two compartment model
      (WinNonlin). For the 2 and 20 mg/kg doses, respectively, the parameter values
      were, area under the plasma concentration-time curve (11.2 and 82.3 micromol
      h/l), total body clearance (0.640 and 0.903 l/h per kg), distribution half-life
      (4.13 and 8.23 h), elimination half-life (54.9 and 58.6 h), volume of the central
      compartment (3.83 and 13.9 l/kg), volume of distribution at steady state (6.06
      and 26.8 l/kg), and the mean residence time (9.57 and 22.7 h). After oral
      administration, the following parameter values were assessed using a model
      independent method, peak concentration (3.03 micromol/l), time of concentration
      peak (8.80 h), mean absorption time (13.8 h), and area under curve (AUC)(0-
      >infinity) (90.2 micromol h/l). A two compartment model analysis of the average
      plasma concentration-time profile after oral administration showed that
      absorption followed first-order kinetics with a half-life of 4.7 h. The oral
      bioavailability of methyltestosterone from food was about 70%.

PMID- 11239681
TI  - Relationships between tissue concentrations of polycyclic aromatic hydrocarbons
      and antioxidative responses of marine mussels, Perna viridis.
AB  - Local mussels, Perna viridis, were transplanted from a relatively clean site to
      various polluted sites in Hong Kong. After a 30-day field exposure, different
      antioxidant parameters including glutathione S transferase (GST), superoxide
      dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione
      reductase (GR), NADPH DT-diaphorase (DT-d), glutathione (GSH) and lipid
      peroxidation were quantified, and tissue concentrations of benzo[a]pyrene (B[a]P)
      as well as a total of five polycyclic aromatic hydrocarbons (PAHs) with potential
      carcinogenicity were determined for individual mussels. Results indicated that:
      (1) tissue concentrations of B[a]P and total PAHs from the same site were highly
      variable; (2) gill SOD, DT-d and lipid peroxidation showed no response to tissue
      pollutants; (3) the majority of the antioxidant parameters were induced by
      increasing tissue pollutant concentrations; and (4) amongst the various
      parameters, oxyradical scavenger GSH best correlated with tissue concentrations
      of pollutants.

PMID- 11239682
TI  - Relationship between allozyme genotype and sensitivity to stressors in the
      western mosquitofish Gambusia affinis detected for elevated temperature but not
      mercury.
AB  - Previous studies with Gambusia holbrooki have found associations of allozyme
      genotype with tolerance to metals, pesticides, heat, and salinity. To examine the
      generality of these relationships, we looked for similar associations of mercury
      and heat tolerance with allozyme genotype at the GPI-2, MDH-1 and MDH-2 loci in
      its sister species Gambusia affinis. This was done to assess if the loci
      themselves or closely linked loci were associated with mercury tolerance, because
      weaker linkage associations would be unlikely to persist across species
      boundaries. Moreover, the use of two very different types of stress allowed us to
      determine if the higher tolerance of particular allozyme genotypes is specific to
      a certain stress or reflects a higher tolerance to stress in general.
      Associations between genotype and tolerance to mercury and heat were determined
      in laboratory exposures of about 875 fish in each of two exposures where
      tolerance was measured as time-to-death, followed by electrophoresis on cellulose
      acetate gels. For none of the three loci did we find an association of genotype
      with tolerance to mercury. This contrasts with reports of such an association for
      GPI-2 and MDH-1 in G. holbrooki, so our results do not support the hypothesis
      that observed associations between allozyme genotypes and mercury tolerance are
      due to the allozymes or closely linked loci. However, our comparison was weakened
      by a scarcity of the GPI-2 genotypes reported to be mercury sensitive in G.
      holbrooki. Furthermore, rapid mortality in our mercury exposure may have affected
      the ability to detect genotypic differences in survival. The MDH-1 heterozygote
      showed higher tolerance to heat stress compared to homozygotes, although this
      difference was only significant for the most common homozygous genotype. No such
      relationship between MDH-1 and heat stress has been reported in G. holbrooki. We
      found no evidence that associations between allozyme genotype and tolerance are
      similar for different types of stresses, which could be an advantage for using
      allozymes as an indicator of exposure history to a stressor. Our study also
      showed that G. affinis sex and weight influence tolerance to mercury and heat.

PMID- 11239683
TI  - Impairment of mysid (Neomysis integer) swimming ability: an environmentally
      realistic assessment of the impact of cadmium exposure.
AB  - Neomysis integer (Crustacea: Mysidacea), a euryhaline member of the hyperbenthos
      of the upper reaches of European estuaries, has been identified as a suitable
      animal for assessing the impacts of chemical pollutants on these estuarine
      regions. In this study, the effect of a 7 day pre-exposure to environmentally
      relevant concentrations of cadmium (0.5 and 1.0 microg l(-1)) on the swimming
      behaviour of N. integer was examined using an annular flume. Cadmium speciation
      at two salinities (1 and 10 per thousand) that dominate these upper estuarine
      regions was modelled to ensure mysids were exposed to the same concentration of
      the toxic free-ion at each salinity. There was no significant difference in the
      swimming behaviour of mysids exposed to the same free-ion cadmium concentration
      at the two different salinities. At each salinity, exposure to 0.5 microg Cd2+
      (aq) l(-1)resulted in fewer mysids moving forward into the current (normal
      behaviour) at free stream velocities typical of their natural habitat (e.g. 3-9
      cm s(-1)) than non cadmium-exposed mysids. At these low current speeds, cadmium
      exposed mysids were either able to maintain position or were swept by the
      current. The same general responses were recorded for mysids exposed to 1.0
      microg Cd2+ (aq) l(-1)except that more mysids showed disrupted swimming ability
      compared with 0.5 microg Cd2+ (aq) l(-1). At higher current speeds (>12 cm s(
      1)), current velocity was the dominant factor affecting mysid swimming behaviour
      and there was no effect of cadmium on mysids maintaining position. Exposure to
      cadmium also caused significant disruption of the hyperbenthic behaviour of N.
      integer and more cadmium-exposed individuals were in the water column than
      control mysids; this result was more variable at 10 per thousand than 1 per
      thousand. Results indicate that exposure to cadmium concentrations of 0.5 microg
      Cd2+(aq) l(-1)would result in displacement of N. integer from its optimum region
      within the estuarine environment. This conclusion would not be achieved from
      standard LC(50) tests (e.g. 7 day LC50 = 2.95 microg Cd2+ (aq) l(-1)),
      highlighting the value of behavioural disruption as a sensitive indicator of
      environmental chemical contamination.

PMID- 11239684
TI  - The use of thiamine and thiamine antagonists to investigate the etiology of early
      mortality syndrome in lake trout (Salvelinus namaycush).
AB  - Early mortality syndrome (EMS) is a non-infectious disease affecting lake trout
      and other salmonids in the Great Lakes and in inland lakes. It is characterised
      by loss of equilibrium, hyperexcitability, anorexia, and eventually death. EMS is
      associated with low thiamine and treatment of eggs or fry with thiamine-HCl
      eliminates symptoms and mortality. To verify the role of the active form of the
      vitamin as the prophylactic agent, we used thiamine pyrophosphate (TPP) to
      reverse EMS symptoms. We also investigated the ability of specific thiamine
      antagonists that either block TPP production or interfere with its function to
      induce EMS. When graded doses of TPP were administered to EMS-susceptible sac
      fry, there was a dose-dependent reduction in EMS. The egg concentration of TPP
      that was associated with reduced EMS was similar to the threshold thiamine
      concentration found in feral lake trout stocks where EMS occurs. A thiamine
      deficient stock from Lake Ontario was very sensitive to the thiamine antagonist
      oxythiamine (OXY) with total mortality associated with developmental arrest
      occurring at an antagonist to thiamine molar ratio (ATR) above 7:1. The threshold
      ATR with OXY for development of EMS-like neurological signs in this stock was
      1.6:1. In addition to EMS-like neurological signs, OXY caused dose-dependent
      increases in hydrocephalus, developmental arrest, and vitelline congestion in the
      Lake Ontario stock. These signs are consistent with those observed in feral fish
      exhibiting EMS. Much higher doses of antagonists were required (both pyrithiamine
      (PT) and OXY) to induce EMS-like clinical signs in the thiamine replete Lake
      Manitou stock. PT was a more potent inducer in this stock as the ATR associated
      with development of clinical signs was 111:1 for PT compared with 892:1 for OXY.
      These data provide experimental evidence supporting the hypothesis that a
      thiamine deficiency in the natural environment is the cause of EMS.

PMID- 11239685
TI  - Phytochelatin production in freshwater algae Stigeoclonium in response to heavy
      metals contained in mining water; effects of some environmental factors.
AB  - Production of phytochelatins (PC) in two freshwater, filamentous green algae of
      the genus Stigeoclonium, in response to heavy metals contained in mining water
      was studied. Stigeoclonium sp. grown abundantly in ditches with the mining water
      (southern Poland) accumulated high amounts of heavy metals. The other studied
      alga Stigeoclonium tenue Kutz. was isolated from unpolluted lake water in the
      Netherlands. Both algae exposed to the heavy metal mixture (17 microM; mainly
      zinc) contained in the hard, alkaline (pH 8.2) mining water produced similar
      amounts of phytochelatins (PC2 and PC3): 500-600 nmol SH g(-1) dry weight. After
      water acidification to pH 6.8, a > 2-fold increase of the total phytochelatin
      level as well as the appearance of longer chain peptide PC4 in the cells of both
      algae was observed. The concentration of labile forms of zinc in the acidified
      mining water was four times as high as that in the alkaline water. The heavy
      metal mixture (17 microM) in non-complexing solution of pH 6.8 caused a
      comparable phytochelatin production in both Stigeoclonium strains as the same
      mixture present in the acidified mining water. However, in the non-complexing
      solution of pH 8.2, the metal mixture induced in algae more PCs than at pH 6.8. A
      positive effect of bicarbonate enrichment in the solution on the PC production in
      S. tenue was also observed. Stigeoclonium sp. exposed to high concentrations (10
      microM) of individual metals (Zn, Pb and Cd available as free cations)
      synthesised much higher amounts of phytochelatins (PC2-PC4) than in response to
      the metal mixture contained in the mining water. The order of PC induction by the
      studied metals in the Stigeoclonium sp. was Cd > Pb > Zn. Addition of suspended
      solid matter to the heavy metal solution resulted in essential quantitative
      changes in phytochelatins in algal cells; a considerable decrease of PC2, PC3 and
      PC4 levels was observed. The PC production in algae of the genus Stigeoclonium
      exposed to the heavy metal mixture is discussed in the context of various metal
      bioavailability and the algal adaptation to complex aquatic environment.

PMID- 11239686
TI  - Identifying body residues of HCBP associated with 10-d mortality and partial life
      cycle effects in the midge, Chironomus riparius.
AB  - The relationship between the body residue of 2,2',4,4',5,5'-hexachlorobiphenyl
      (HCBP) and its effects, including 10-d mortality and chronic sublethal effects on
      the midge, Chironomus riparius, are examined in a partial life cycle assessment.
      The alga, Chlorella vulgaris, was loaded with 14C-labeled HCBP and fed to midges
      as the method for delivery of the toxicant. In a 10-d bioassay, median lethal
      body residue (LR50) was 0.57 (95% CI: 0.49-0.66) mmol/kg. In the partial life
      cycle test, midges were fed a mixture of 12C- and 14C-HCBP-laden algae and
      exposed in four separate tests to assess the different developmental stages
      representing 2nd to 3rd instar, 2nd to 4th, 2nd to pupa, and 2nd to adult stages.
      A variety of sublethal endpoints were monitored, including developmental time
      within a stadium, body concentration at the end of each stadium, body weight, and
      fecundity (the number of ova) for the female pupae and adults. Overall, midge
      body concentrations of HCBP increased with increasing exposure concentration.
      Body weight was not significantly affected by HCBP except during the 4th instar.
      Body residue also increased with each successive stadium. Developmental time
      increased significantly with increasing body concentration in 2nd to 4th, 2nd to
      pupa, and 2nd to adult tests, while there was no statistical significance in
      developmental time for the 2nd to 3rd instar test. The number of ova decreased
      significantly in adults with increasing body concentration of HCBP, with an
      average of 345 ova in controls, 289 ova at 0.028 mmol/kg of HCBP, and 258 ova at
      0.250 mmol/kg. These data, which relate chronic endpoints to body residues,
      suggest that sublethal endpoints in invertebrates are useful for defining
      sublethal hazards of PCBs. These data also suggest that ecological consequences
      may result from relatively low body burdens of PCBs.

PMID- 11239687
TI  - Dynamics of (Cd,Zn)-metallothioneins in gills, liver and kidney of common carp
      Cyprinus carpio during cadmium exposure.
AB  - Cadmium concentrations, (Cd,Zn)-metallothionein (MT) concentrations, MT synthesis
      and the relative amounts of cadmium bound to (Cd,Zn)-MTs were determined in
      gills, liver and kidney of common carp Cyprinus carpio exposed to 0, 0.5 microM
      (0.06 mg.l(-1)), 2.5 microM (0.28 mg.l(-1)) and 7 microM (0.79 mg.l(-1)) Cd for
      up to 29 days. Cadmium accumulation was in the order kidney > liver > gills.
      Control levels of hepatic (Cd,Zn)-MT were four times higher compared to those of
      gills and kidney. No increases in (Cd,Zn)-MT concentrations were observed in
      liver during the exposure period. In comparison with control carp, (Cd,Zn)-MT
      concentrations increased up to 4.5 times in kidney and two times in gills. In
      both these organs, (Cd,Zn)-MT concentrations were linearly related with cadmium
      tissue levels and with the de novo synthesis of MTs. Hepatic cadmium was almost
      completely bound to (Cd,Zn)-MT, while percentages of non-MT-bound cadmium were at
      least 40% in gills and 25% in kidney. This corresponded with a total saturation
      of (Cd,Zn)-MT by cadmium in kidney and a saturation of approximately 50 and 60%
      in gills and liver, respectively. The final order of non-MT-bound cadmium was
      kidney > gills > liver. Our results indicate that cadmium exposure causes toxic
      effects, which cannot be correlated with the accumulated levels of the metal in
      tissues. Although cadmium clearly leads to the de novo synthesis of MT and higher
      (Cd,Zn)-MT concentrations, the role of this protein in the detoxification process
      is clearly organ-specific and its synthesis does not keep track with cadmium
      accumulation.

PMID- 11239688
TI  - Further considerations of the skeletal system as a biomarker of episodic
      chlorpyrifos exposure.
AB  - The mummichog, Fundulus heteroclitus, is a common inhabitant of eastern seaboard
      estuaries. As such, it can be affected by coastal agricultural and other nonpoint
      source runoff. We examined the effects of short-term episodic exposures to an
      agricultural pesticide, chlorpyrifos, on brain acetylcholinesterase (AChE)
      activity and vertebral yield strength in lab-reared and wild-caught fish. Brain
      AChE activity was chosen as an indicator because it is the target system for
      organophosphate action. Vertebral yield strength was chosen as an indicator
      because previous research warranted further investigation (Karen et al., 1998).
      Four daily or weekly 6 h exposures (2.5, 5.0, and 10.0 microg/l chlorpyrifos) in
      decreased salinity seawater (5 g/kg) significantly reduced brain AChE activity.
      The lowest concentration was within the range of reported environmental
      chlorpyrifos concentrations; thus inhibition of brain AChE from environmental
      chlorpyrifos exposures may pose a hazard to estuarine organisms. Yield strength
      measured in lab-reared fish appeared to be more sensitive to episodic
      chlorpyrifos exposures, because chlorpyrifos was a significant factor in 75% (3
      out of 4) of tests performed with lab-reared fish. Chlorpyrifos exposure was a
      significant factor in only 25% (1 out of 4) tests performed with wild fish. These
      results suggested that changes in the responses of bone to load testing,
      following several short exposures to an organophosphate, could be sensitive
      indicators in lab-reared organisms.

PMID- 11239689
TI  - Immunochemical and catalytic characterization of hepatic microsomal cytochrome
      P450 in the sperm whale (Physeter macrocephalus).
AB  - Liver samples from three live-stranded adult male sperm whales, that could be
      sampled and frozen in liquid nitrogen within 18 h post mortem, provided an
      opportunity to learn more about the basic properties of their cytochrome P450
      (CYP) system. All samples were catalytically active and showed sharp bands of the
      different CYP enzymes after Western blotting, indicating that degradation of the
      proteins was negligible. All three sperm whales showed a similar immunochemical
      CYP pattern: bands of CYP1A1/2, CYP3A and CYP4A were present, but CYP2B1/2 was
      not detected. Significant biotransformation of the polychlorinated aromatic
      hydrocarbons 4, 4'-dichlorobiphenyl (CB-15), 2,7-dichlorodibenzodioxin and
      1,2,3,4,8-pentadibenzofuran was measured in an in vitro biotransformation assay.
      In contrast, 3,3',4,4'-tetrachlorobiphenyl (CB-77) and two chlorobornanes (CHB-32
      and CHB-62) occurring in the insectide toxaphene(R), were not metabolised.

PMID- 11239690
TI  - Are metal mining effluent regulations adequate: identification of a novel
      bleached fish syndrome in association with iron-ore mining effluents in Labrador,
      Newfoundland.
AB  - Water quality guidelines for industrial effluents are in place in many countries
      but they have generally evolved within a limited ecotoxicological framework.
      Effluents from iron-ore mines have traditionally been viewed by regulatory bodies
      as posing little or no risk to the aquatic environment. However, it was recently
      reported that lake trout taken from a large iron-ore contaminated Lake in
      Labrador (Wabush Lake) had elevated levels of DNA oxidative damage and were
      markedly depleted in levels of vitamin A (Payne et al., 1998) in comparison with
      fish from a Lake (Shabogamo Lake) receiving lesser levels of effluents. Through
      further observations, it has now been established that the lake trout in Wabush
      Lake are commonly affected with a marked skin bleaching syndrome in comparison
      with fish in Shabogamo Lake and a nearby Lake (Ashuanipi) which does not receive
      effluents. To the authors' knowledge such a syndrome which is characterized by
      marked reduction in skin pigmentation and overall increase in skin whitening has
      not been reported before in any fish population in association with
      contamination. Preliminary information for liver histopathological and blood cell
      differences have also been obtained in fish in Wabush Lake in comparison with
      Ashuanipi Lake. It has also been observed through studies on phosphatidyl
      liposomes that iron-ore leachate contains redox-active material (iron but
      possibly other transition metals) that has considerable potential for causing
      oxidative damage to cellular constituents. Using the weight of evidence approach
      it is indicated that iron-ore effluents may pose more of a risk to the aquatic
      environment than traditionally considered by regulatory agencies.

PMID- 11239691
TI  - Persistence of benzo[a]pyrene--DNA adducts in hematopoietic tissues and blood of
      the mummichog, Fundulus heteroclitus.
AB  - The formation and persistence of benzo[a]pyrene (B[a]P)-DNA adducts were
      investigated in blood, liver and two hematopoietic tissues (anterior kidney and
      spleen) of the mummichog (Fundulus heteroclitus). Fish were injected with a
      single, sublethal dose of B[a]P (12 mg/kg body weight) and sampled from 8 to 96
      days post-injection. 32P-Postlabeling analysis and storage phosphor imaging were
      used to resolve and quantify hydrophobic DNA adducts. One major DNA adduct was
      present in each of the examined tissues at all sampling times. This adduct had
      similar chromatographic characteristics to those of the adduct standard, 7R,8S,9S
      trihydroxy-10S-(N(2)-deoxyguanosyl-3'-phosphate)-7,8,9,10-tetrahydro
      benzo[a]pyrene (B[a]PDE-dG). Minor DNA adduct spots, representing less than 2% of
      the total DNA adducts, were observed in some liver, anterior kidney and spleen
      samples for up to 32 days post-injection. The B[a]P-DNA adducts reached maximal
      levels at 32 days post-injection and persisted for at least 96 days in all
      examined tissues. B[a]P-DNA adduct levels were significantly higher in the liver
      and anterior kidney than in the spleen from 16 to 96 days (P<0.001), although
      liver and anterior kidney DNA adduct levels were not significantly different at
      any time. This is the first controlled study to demonstrate the formation and
      persistence of B[a]P-DNA adducts in hematopoietic tissues and blood of fishes
      exposed to the prototypical polycyclic aromatic hydrocarbon, B[a]P. Although
      persistent DNA adducts are generally recognized as potential initiators of
      carcinogenic processes, adducts in these vital tissues may also lead to
      disruption of physiological functions such defense mechanisms and hematopoiesis.

PMID- 11239692
TI  - Normalized pulse volume (NPV) derived photo-plethysmographically as a more valid
      measure of the finger vascular tone.
AB  - Normalized pulse volume (NPV) was advocated as a more valid measure for the
      assessment of finger vascular tone. Based on the optical model in the finger tip
      expressed by Lambert--Beer's law, NPV is expressed as Delta I(a)/I. Here, Delta
      I(a) is the intensity of pulsatile component superimposed on the transmitted
      light (I). Theoretically, NPV seems to be superior to the conventional pulse
      volume (PV; corresponding to Delta I(a)). Firstly, NPV is in direct proportion to
      Delta V(a), which is the pulsatile component of the arterial blood volume, in a
      more exact manner. Relatedly, NPV can be processed as if it is an absolute value.
      Secondly, the sensitivity of NPV during stressful stimulations is expected to be
      higher. These expectations were supported experimentally using 13 male students.
      Firstly, the correlation between cutaneous vascular resistance in the finger tip
      (CVR) and NPV was higher than that between CVR and PV among all the subjects,
      although there was not much difference between these correlations within each
      subject. Secondly, NPV decreased much more than PV during mental stress. Some
      limitations of the present study were addressed, including the point that certain
      factors can violate the direct proportional relationship of NPV and PV to Delta
      V(a).

PMID- 11239693
TI  - Emotional memories: the relationship between age of memory and the corresponding
      psychophysiological responses.
AB  - The recollection of emotional memories has been used as a method of emotion
      induction for much of the research concerning the psychophysiological sequelae of
      emotions. The instructions used in most of these investigations have simply
      required the participants to recollect or imagine an emotional memory, with no
      constraint being placed on the age of the memory. Research has indicated that the
      specific instructions for inducing emotions can have a profound effect on the
      resulting patterns of psychophysiological arousal. The present investigation
      concerned whether the age of the emotional memory has an influence on the
      resulting psychophysiological arousal. Heart rate and skin conductance was
      recorded from 10 female graduate students while they recollected emotional
      memories concerning mirth and anger. The results indicated a significant positive
      correlation between skin conductance and age of both the angry (0.6395) and the
      mirthful (0.8460) memories. The results are discussed and explained within the
      framework of the somatic marker hypothesis and the spreading activation model of
      memories.

PMID- 11239694
TI  - Elite pistol shooters: physiological patterning of best vs. worst shots.
AB  - This study examined patterns of physiological activity in elite pistol shooters
      and compared them with novice shooters. Heart rate and electrodermal activity
      were recorded for three 150-s epochs. Participants performed part of the Standard
      Pistol Shooting Protocol, firing five rounds at a target 25 m distant within the
      first 150 s epoch. In the second epoch, baseline data were recorded with the
      participant standing at rest. The third epoch was a repetition of the first
      epoch. For each shot, values of heart rate and skin conductance were calculated
      at half-second intervals from 20 s before to 10 s after the shot. In experts
      there was a slow reduction in skin conductance and heart rate levels prior to the
      shot, and a 'rebound' increase immediately following the shot, which were not
      apparent in the novice shooters. Pre-shot electrodermal levels for the expert
      shooters were lower for the best compared with the worst shots, and the duration
      of the pre-shot cardiac deceleration was longer and more systematic for best than
      for worst shots. The physiological profiles supported interpretation in terms of
      two separate state processes, arousal and vigilance, rather than a single
      construct. These physiological differences are discussed in terms of differential
      engagement with the task and its associated attentional narrowing in expert
      pistol shooters.

PMID- 11239695
TI  - Does a warning signal accelerate the processing of sensory information? Evidence
      from recognition potential responses to high and low frequency words.
AB  - Electrophysiological and behavioral data were obtained in 12 subjects who
      detected valid words in a background stream of random letter strings. Behavioral
      reaction time (RT) showed significant effects of warning signal presentation and
      the frequency of word usage in printed literature. Cross-correlation functions
      were used to estimate delays of electrophysiological responses. The critical
      response was the recognition potential (RP). The RP is a response of the brain
      that occurs when a person views recognizable images, such as words, pictures, or
      faces. Its latency is usually less than 300 ms. Both the RP and longer latency
      activity occurring at approximately 400--600 ms were delayed more for low than
      for high frequency words. The longer latency responses showed shorter delay if a
      warning signal was presented, but the RP did not. The results supported the idea
      that a non-informative warning signal decreases RT by altering response-related
      processes without facilitating sensory processes.

PMID- 11239696
TI  - Effect of the relevance and position of the target stimuli on P300 and reaction
      time.
AB  - The relationships among stimulus relevance and the position of target stimuli in
      a sequence with the P300 component of event related brain potentials and reaction
      time were investigated. An auditory oddball series was presented to 42 healthy,
      young, right-handed female participants. In the series, participants were to
      ignore the standard stimuli and count the deviants from 1 to 6. When reaching the
      count of 6, they had to restart their count from 1 again. While counting, half of
      the sample had to press a key after the deviants, numbers 1, 2 and 3, but not
      after the numbers 4, 5 and 6. The other half of the sample had to press the key
      when numbers 4, 5 and 6 rather than when numbers 1, 2, 3 appeared. The P300
      amplitude of the more relevant (count and press) stimuli was higher than that of
      the P300 amplitude of the less relevant (count only) stimuli. This is associated
      with a greater allocation of cognitive resources to the more relevant stimuli. An
      interaction was also found between the position of the target stimuli in a
      sequence and the stimulus relevance, which is attributed to the cognitive
      preparation. Furthermore, the reaction time tended to increase along the sequence
      of the more relevant stimuli, due perhaps to an increase in physical fatigue.

PMID- 11239697
TI  - Facial and autonomic activity in depression: social context differences during
      imagery.
AB  - Previous research indicates that depressed patients show reduced facial
      expression as well as a lack of social context differences in frowning in
      response to sad imagery. The present study examined social context differences in
      facial electromyogram (EMG), self-reported emotion, skin conductance level and
      heart rate in 21 depressed and 22 non-depressed women assessed by the Beck
      Depression Inventory. Subjects were asked to imagine happy and sad situations
      both with and without visualizing other people. Depressed subjects showed a lack
      of social context differences in EMG-brow activity during sad imagery while heart
      rate was increased during sad-social compared to sad-solitary imagery. In
      contrast, non-depressed subjects showed increased EMG-brow activity during sad
      social compared to sad-solitary imagery but no social context differences in
      heart rate. EMG-cheek activity and heart rate were increased during happy-social
      compared to happy-solitary imagery in depressed and non-depressed subjects. Skin
      conductance level was reduced in depressed compared to non-depressed subjects
      during baseline but failed to respond to imagery. Social context differences in
      heart rate and a lack thereof of frowning during sad imagery may indicate an
      altered psychosocial functioning in depression.

PMID- 11239698
TI  - Cardiovascular (CV) responsivity and recovery to acute stress and future CV
      functioning in youth with family histories of CV disease: a 4-year longitudinal
      study.
AB  - Blood pressure (BP) and heart rate (HR) data obtained during supine rest, in
      response to and recovery from four laboratory stressors in a baseline year were
      used to predict supine resting BP and HR values obtained during each of four
      consecutive annual follow-up evaluations. Subjects were 385 normotensive youth
      [95 African American (AA) males, 106 AA females, 92 European American (EA) males,
      92 EA females] (mean age 12.7+/-2.6 at baseline year) with a positive family
      history of cardiovascular disease (CVD). During the baseline evaluation subjects
      were presented with four laboratory stressors (namely, postural change, video
      game challenge, social competence interview, and parent--child conflict
      discussion). The BP and HR values taken during each of the laboratory stressors
      and during the post stressor recovery periods were converted to z-scores which
      were averaged to yield aggregate measures for systolic and diastolic BP and HR
      responsivity and recovery. The data obtained during the baseline evaluation were
      subsequently used to predict the follow-up values of supine resting BP and HR.
      The prediction models were fairly consistent across each of the 4 follow-up
      years. Responsivity or recovery accounted for up to 6% of the total variance
      after accounting for baseline values. Within the prediction models responsivity
      or recovery accounted for 4--56% of the variance. The predictive value of the
      derived models did not decline from one annual evaluation to the next over the
      length of the study. CV recovery may supplement resting and responsivity in the
      prediction of future development of CVD

PMID- 11239700
TI  - Psychophysiological correlates of the NEO PI-R openness, agreeableness and
      conscientiousness: preliminary results.
AB  - Eysenck (1983) has previously proposed biological mechanisms for his three
      personality dimensions. From a psychometric perspective there has been a growing
      acceptance of a five-factor model of personality incorporating two of Eysenck's
      dimensions Extraversion (E) and Neuroticism (N) together with Openness to
      Experience (O), Agreeableness (A) and Conscientiousness (C). Despite the growing
      acceptance of the 'Big 5' model of personality there has been very few studies
      that have examined the biological basis of O, A and C. In an exploratory study we
      report the correlations between photic driving at alpha, beta-1, beta-2, delta
      and theta bands and O, A and C from the NEO PI-R in 16 participants. Significant
      correlations between the EEG at frontal, occipital-parietal and central-temporal
      areas at different driving frequencies with O, A and C are discussed.

PMID- 11239699
TI  - Emotion, attention, and the 'negativity bias', studied through event-related
      potentials.
AB  - Behavioral studies indicate that there exists a 'negativity bias' in the way
      surrounding events are processed. Particularly, it has been indicated that
      negative events elicit more rapid and more prominent responses than non-negative
      events. The objective of the present study was to explore the role of attention
      in relation to this negativity bias. Three groups of emotional pictures were used
      as stimuli: positive, negative and neutral. Event-related potentials were
      recorded from 35 subjects at F5, Fz, F6, C5, Cz, C6, P5, Pz and P6. Valence and
      arousal content of the stimulation was measured via a questionnaire. The
      experimental design ensured that subjects whose data were finally analyzed
      attended to the stimuli. ANOVAs showed that P200, an attention-related component,
      showed higher amplitudes and shorter latencies in response to negative stimuli
      than in response to positive stimuli. Additional partial correlation analyses
      indicated that P200 amplitude, but not latency, significantly associates (at
      frontal and central sites) with valence content of the stimulation. Therefore,
      due to the valence-related nature of the bias, it is concluded that intensity
      aspects (more than timing aspects) of the P200-related attentional processes are
      particularly involved in the negativity bias.

PMID- 11239701
TI  - The effect of a short-term mental stressor on neutrophil activation.
AB  - Twenty-five undergraduates and university staff (15 females, 10 males)
      volunteered to take part in a study examining the effects of a short-term mental
      stressor on the activation of neutrophils in peripheral blood, as determined by
      the oxidative capacity to reduced Nitro-blue Tetrazolium (NBT). Participants were
      assigned to one of two groups, an experimental group (n=17) and a control group
      (n=8). Subjects in the experimental group were subjected to a time-constrained
      mental stressor and finger-stick blood samples were taken on four occasions.
      Those in the control group did not complete a stressor task and only experienced
      the four finger-stick blood samples. Heart rate was recorded at 5-min intervals
      as a general indicator of arousal. Examination of the stained blood samples
      showed that a short-term stressor resulted in significant increased activation of
      neutrophils, which returned almost to baseline levels on completion of the
      experiment. In contrast, the control group's neutrophils showed no significant
      change in activation throughout. The results support the hypothesis that short
      term, acute stressors may activate neutrophils.

PMID- 11239702
TI  - Acetyl-L-carnitine enhances Na(+), K(+)-ATPase glutathione-S-transferase and
      multiple unit activity and reduces lipid peroxidation and lipofuscin
      concentration in aged rat brain regions.
AB  - This study investigated the effects of chronically administered acetyl-L
      carnitine (ALC) on sodium potassium adenosine triphosphatase (Na(+), K(+)
      ATPase), glutathione-S-transferase (GST), glutathione peroxidase (GPx), multiple
      unit activity (MUA) and lipid peroxidation (LP) and lipofuscin (LF) concentration
      in brain regions: cerebral cortex, hippocampus, striatum and thalamus, of 24
      month-old rats. The activity of Na(+), K(+)-ATPase and GST was enhanced; that of
      GPx was unaffected. The MUA was increased while the levels of LP and LF were
      decreased. These novel data provide new additional evidence concerning the
      antiaging attributes of ALC.

PMID- 11239704
TI  - An electrophysiological test of the effect of the temporal pattern of light
      adaptation on teleost H1 type horizontal cell plasticity.
AB  - The possible importance of the temporal pattern of photon delivery in light
      adaptation-induced physiological plasticity in the outer retina of carp was
      tested by intracellular recording. Steady and flicker (3 Hz) background
      adaptation was applied whilst recording chromatic voltage responses of H1 type
      horizontal cells (HCs) to 680 and 440 nm full-field test flashes (generating
      response amplitudes of V(r) and V(b), respectively). A third parameter V(b)/V(r)
      (B/R) was calculated as an indicator of the cells' short/long wavelength relative
      spectral contrast. Steady light adaptation increased V(r) and to a lesser extent
      V(b), and reduced B/R. Flicker adaptation also increased V(r) (by a similar
      amount), but, unlike steady adaptation, consistently decreased V(b). The
      reduction in B/R was statistically greater for flicker than for steady
      adaptation, although the former delivered half as many photons to the retina.
      These results suggest that the temporal pattern of light adaptation is indeed an
      important determinant of qualitative and quantitative aspects of plasticity
      induced in the outer retina, and complement earlier morphological findings. The
      effects are discussed in terms of dopamine and nitric oxide as underlying
      possible neurochemical control mechanisms.

PMID- 11239703
TI  - Deafferentation of the hippocampus results in the induction of AT8 positive
      'granules' in the rat.
AB  - Hyperphosphorylated tau is a pathological hallmark of Alzheimer's disease, but
      the mechanisms that lead to its formation are poorly understood. To investigate
      what effect deafferentation of the hippocampus has on the phosphorylation state
      of tau, we lesioned the entorhinal cortex in rats and looked for
      hyperphosphorylated tau in the hippocampus at various days post lesioning. After
      7 and 21 days, small AT8-positive 'granules' appeared in the molecular layer of
      the dentate gyrus on the lesioned side. No such staining was seen in the animals
      injected with saline. This study shows that deafferentation leads to induction of
      hyperphosphorylated tau. The AT8 positive 'granules' seen resemble the
      argyrophilic grains that characterize Argyrophilic Grain disease suggesting that
      lesioning the perforant pathway may serve as a useful model for inducing
      argyrophilic grains in vivo.

PMID- 11239705
TI  - Differential coupling of voltage-gated Ca(2+) channels to catecholamine secretion
      from separate PC12 cell batches.
AB  - Amperometric recordings were employed to investigate the coupling of Ca(2+)
      channels to catecholamine secretion in two batches of pheochromocytoma (PC12)
      cells. In 'new' (freshly obtained) cells (PC12n cells), secretion was dependent
      on Ca(2+) influx through L-type and N-type Ca(2+) channels. By contrast, in
      'aged' cells (maintained in liquid nitrogen for 6-8 years; PC12a cells),
      secretion was mostly dependent on Ca(2+) influx through N-type channels. Patch
      clamp recordings revealed that L-type channels accounted for only ca. 26% of
      total whole-cell current in PC12a cells (determined by blockade caused by 2
      microM nifedipine). In contrast, nifedipine suppressed currents by ca. 59% in
      PC12n cells. Thus important differences in fundamental physiological properties
      can be observed in PC12 cell batches even when obtained from the same source and
      maintained under identical conditions.

PMID- 11239706
TI  - Differential antinociceptive effect of transcutaneous electrical stimulation on
      pain behavior sensitive or insensitive to phentolamine in neuropathic rats.
AB  - The effects of transcutaneous electrical stimulation and systemic injection of
      phentolamine, a non-specific alpha-adrenergic antagonist, on the behavioral signs
      of mechanical allodynia and cold hyperalgesia in rats with nerve injury were
      investigated. Mechanical allodynia and cold hyperalgesia were evaluated by
      measuring the paw withdrawal frequency (PWF) resulting from repetitive
      application of a von Frey hair and the paw lift duration (PLD) at a cold
      temperature, respectively. After a unilateral nerve injury, both PWF and PLD
      increased in the injured hind paw. Application of low-frequency, high-intensity
      transcutaneous electrical stimulation (LFHI-TES) to the injured hind paw
      depressed the injury-induced increased PWF, whereas it had no effect on the
      injury-induced increased PLD. Naloxone reversed the LFHI-TES produced depression
      of PWF. Intraperitoneal administration of phentolamine depressed the injury
      induced increased PLD without affecting the injury-induced increased PWF. Our
      results suggest that LFHI-TES, which activates the endogenous opioid systems,
      produces an antinociceptive effect that appears to be related to whether or not
      the pain is mediated by sympathetic activity.

PMID- 11239707
TI  - Heterogeneous responses of aquaporin-4 in oedema formation in a replicated severe
      traumatic brain injury model in rats.
AB  - Aquaporin-4 (AQP4) is the most abundant water channel in the rat brain. In this
      study, the distribution pattern and mRNA expression levels of AQP4 were examined
      in a severe traumatic brain injury model by immunohistochemistry and reverse
      transcription-polymerase chain reaction. Oedema formation and blood-brain barrier
      (BBB) integrity were assessed by wet-dry weight measurements and immunostaining
      of endogenous IgG respectively. In the oedematous contusional cortex with
      impaired BBB integrity, negative immunostaining of AQP4 and down-regulation of
      its mRNA level were identified (P<0.05) at 1 day post-injury, while in other
      oedematous regions of the injured brain where BBB was intact, there was no
      significant change in the AQP4 expression level. This heterogeneous pattern of
      AQP4 responses can be interpreted as follows: focal brain injury (such as a
      contusion) with impaired BBB resulting in vasogenic oedema is associated with
      reduction of AQP4 expression, whereas, in cytotoxic oedema, associated with
      diffuse brain injury with intact BBB, changes in AQP4 expression are not
      significant. This study provides basic information for investigating new
      treatments for traumatic brain oedema.

PMID- 11239708
TI  - Visual feedback of the moving arm allows complete adaptation of pointing
      movements to centrifugal and Coriolis forces in human subjects.
AB  - A classical visuo-manual adaptation protocol carried out on a rotating platform
      was used to test the ability of subjects to adapt to centrifugal and Coriolis
      forces when visual feedback of the arm is manipulated. Three main results emerge:
      (a) an early modification of the initial trajectory of the movements takes place
      even without visual feedback of the arm; (b) despite the change in the initial
      trajectory, the new external force decreases the accuracy of the pointing
      movements when vision is precluded; (c) a visual adaptive phase allows complete
      adaptation of the pointing movements performed in a modified gravitoinertial
      field. Therefore vision would be essential for subjects to completely adapt to
      centrifugal and Coriolis forces. However, other sensory signals (i.e. vestibular
      and proprioceptive) may constitute the basis for early but partial correction of
      the pointing movements.

PMID- 11239709
TI  - The imidazoline receptor ligand 2-(2-benzofuranyl)-2-imidazoline is a dopamine
      releasing agent in the rat striatum in vivo.
AB  - 2-BFI (2-(2-benzofuranyl)-2-imidazoline) is a prototypical I2-imidazoline
      receptor ligand. In vivo, however, 2-BFI (1-20 mg/kg) decreased the synthesis of
      dopa/dopamine (DA) in rat striatum through mechanisms not related to interaction
      with I2-imidazoline receptors or to inhibition of the enzyme monoamine oxidase.
      The aim of this study was to unravel the mechanism underlying this potent effect
      of 2-BFI in brain. In vitro 2-BFI showed very low affinity for D2-dopamine
      receptors (K(i)=47 microM), and in vivo the drug (7 mg/kg) decreased the
      synthesis of striatal dopa/DA similarly in control rats (43%) and in rats pre
      treated with alpha-methyl-para-tyrosine (50%) or cocaine (51%), indicating that
      this effect was not the result of D2-dopamine autoreceptor direct stimulation,
      inhibition of the enzyme tyrosine hydroxylase or blockade of neuronal DA
      reuptake. In DA-depleted (reserpine-treated) rats, however, 2-BFI did not inhibit
      significantly (11%), the synthesis of dopa/DA in the striatum, indicating that
      the effect of 2-BFI was indirectly mediated by endogenous DA through the
      activation of D2-dopamine autoreceptors. In conclusion, the I2-imidazoline
      receptor ligand 2-BFI is also a DA releasing agent in brain, and consequently a
      DA indirect agonist in vivo.

PMID- 11239710
TI  - Adhesion of adenosine diphosphate-activated platelets to human brain
      microvascular endothelial cells under flow in vitro is mediated via GPIIb/IIIa.
AB  - Employing video-enhanced contrast (VEC) microscopy, we examined whether TAK-029
      (GPIIb/IIIa antagonist) inhibits the adhesion of activated platelets to human
      brain microvascular endothelial cells (HBEC) in vitro. HBECs were cultured on a
      coverglass and put in the observation chamber of VEC microscopy. Then, activated
      platelets by adenosine diphosphate (ADP) (2 microM) were perfused over HBEC at a
      low shear rate of 10 s(-1) for 30 min and washed out. Platelets adhered directly
      to HBEC. However, platelet adhesion to HBEC was suppressed when platelet rich
      plasma with ADP (2 microM) plus TAK-029 (GPIIb/IIIa antagonist; 1 microM) was
      perfused over HBEC for 30 min and washed out. Anti-GPIbalpha antibody (GUR20-5)
      did not inhibit adhesion of ADP-activated platelets to HBEC. The above results
      showed adhesion of ADP-activated platelets to HBEC under flow in vitro is
      mediated via GPIIb/IIIa

PMID- 11239711
TI  - Brain potentials in human patients with extremely severe diffuse brain damage.
AB  - To test higher cortical functions of neurological patients, oddball tasks are
      often used in which a frequent and a rare stimulus are randomly presented and a
      P3 brain wave is recorded to the rare stimulus. We examined 33 patients with
      extremely severe brain injury. Three oddball conditions were used: with two sine
      tones (ST), with two complex tones (CT) and with vowels 'o' and 'i'. Across all
      patients, CT elicited P3 more often than ST, and the occurrence of the P3 after
      vowels was intermediate. However, among patients who showed a distinct P3 wave,
      its amplitude in the subgroup with traumatic brain injury was larger to vowels
      than to CT. In patients with non-traumatic etiology, CT and vowels elicited a P3
      of a nearly equal amplitude. Stimuli of sufficient complexity should be used when
      the P3 technique is applied for assessment of cortical functions in severely
      impaired patients.

PMID- 11239712
TI  - NOTCH4 gene polymorphism and susceptibility to schizophrenia and schizoaffective
      disorder.
AB  - The NOTCH4 gene is located at 6p21.3, a site which several studies have shown to
      have significant linkage with schizophrenia. Recently, an exceptionally strong
      association was reported between NOTCH4 gene polymorphisms and schizophrenia in
      British patients. We re-examined their findings using a Japanese population. We
      genotyped three kinds of polymorphisms, SNP1 in the 5' flanking region, SNP2 in
      the promoter region and CTG repeats in exon 1 of the NOTCH4 gene of
      schizophrenics (N=188), patients with schizoaffective disorder (N=39) and
      controls (N=143). Genotypic distributions and allelic frequencies of SNP1, SNP2
      and CTG repeats of the NOTCH4 gene did not show significant associations with
      schizophrenia or schizoaffective disorder. Neither they showed association with
      schizophrenia subcategories, hebephrenic and paranoid type schizophrenia, nor
      with subgroups of schizophrenia with and without positive family history of
      psychoses. The present study found that the NOTCH4 gene does not confer
      susceptibility to schizophrenia and schizoaffective disorders, at least in
      Japanese subjects, in contrast to the findings in British subjects.

PMID- 11239713
TI  - The transfer of a timing pattern to the untrained human hand investigated with
      functional magnetic resonance imaging.
AB  - The study investigates cortical hemodynamic responses during continuation tapping
      using auditory pacing stimuli in five healthy right-handed subjects using
      functional magnetic resonance imaging. The tasks required the use of either the
      same finger for synchronization of the tapping movement and for continuation, or
      to use the contralateral finger for continuation. Results show, that using the
      contralateral finger increases regional cerebral blood flow in motor areas such
      as the anterior cerebellar hemispheres and vermis, in the cingulate motor area,
      but also in the posterior cingulum, when compared to using the same finger. The
      complementary comparison shows increased regional blood flow in the left
      hippocampus. The results suggest that in addition to pure executive functions,
      higher cognitive functions localized in these areas are involved in the transfer
      of interval timing.

PMID- 11239714
TI  - Melatonin modulates gamma-aminobutyric acid(A) receptor-mediated currents on
      isolated carp retinal neurons.
AB  - Modulation by melatonin of gamma-aminobutyric acid(A) (GABA(A)) receptor-mediated
      responses was studied in bipolar and amacrine-like cells acutely isolated from
      carp retina, using the whole-cell patch-clamp technique. Melatonin of 1 mM
      accelerated desensitization of the GABA(A) receptors at both bipolar and amacrine
      like cells. In addition, 1 mM melatonin hardly changed the GABA(A) receptor
      mediated response amplitude of bipolar cells, while it increased or decreased
      that of amacrine-like cells, depending on the concentration of GABA applied.
      These modulatory effects, which can not be blocked by luzindole, a melatonin
      receptor antagonist, may be due to the allosteric action caused by melatonin
      bound to a site of the GABA(A) receptors.

PMID- 11239715
TI  - Early induction of interleukin-6 mRNA in the hippocampus and cortex of APPsw
      transgenic mice Tg2576.
AB  - The neuropathological changes in Alzheimer's disease (AD) include the occurrence
      of activated microglia and astrocytes. Activated microglia expressing interleukin
      1beta (IL-1beta) and interleukin-6 (IL-6) immunoreactivity have been observed in
      close vicinity of the amyloid plaques in post-mortem tissue from AD patients. In
      order to further analyze the inflammatory process in relation to amyloidosis, we
      have studied the levels of markers for inflammation in the brain of
      Tg(HuAPP695K670N/M671L)2576 transgenic mice (Tg2576) that express high levels of
      human beta-amyloid precursor protein with the Swedish double mutation and develop
      prominent AD type neuropathology. The mRNA levels for IL-1beta, IL-1beta
      converting enzyme (ICE/caspase-1) and IL-6 were analyzed by semi-quantitative
      reverse transcription-polymerase chain reaction in the cerebral cortex,
      hippocampus and cerebellum from Tg2576 and wild type (wt) mice. The levels of
      mRNA for IL-1beta and caspase-1 were not significantly increased in either young
      (4 months) or aged (18 months) Tg2576 mice as compared to the age-matched wt
      mice. However, we observed an increase in IL-6 mRNA levels in the hippocampus and
      cortex of both 4- and 18-month-old transgenic mice as compared to wt mice. The
      increase in IL-6 mRNA levels in Tg2576 animals thus occurs before amyloid plaques
      can be detected (9-10 months). This would indicate that IL-6 mRNA induction is an
      early event in a beta-amyloid-induced immune response cascade or that it may be
      involved in the amyloidosis.

PMID- 11239716
TI  - Dual role of glutamatergic neurotransmission on amyloid beta(1-42) aggregation
      and neurotoxicity in embryonic avian retina.
AB  - The effects of glutamate receptor antagonists on the toxicity of the beta-amyloid
      peptide (Abeta(1-42)) in embryonic chick retina were investigated. When used
      alone or in combination, the N-methyl-D-asparate antagonist, MK-801, the (+/-)
      alphaamino-3-hydroxyl-5-methylisoxazole-4-propionic acid/kainate antagonist,
      DNQX, and the metabotropic receptor antagonist, (RS)-1-aminoindan-1,5
      dicarboxylic acid, blocked the neurotoxicity of Abeta(1-42). Aggregation of
      Abeta(1-42) was significantly increased in the presence of acidic glutamate
      solutions, but not in the presence of other neurotransmitters. These results
      point to a dual role of glutamatergic transmission in Alzheimer's disease (AD):
      (i) Abeta neurotoxicity requires activation of glutamate receptors and its
      blockade prevents cell death; (ii) high concentrations of glutamate in the
      synaptic cleft indirectly enhance Abeta aggregation through acidification of the
      medium, resulting in increased amounts of neurotoxic amyloid fibrils. These
      results suggest that glutamatergic neurotransmission may represent a novel target
      for therapeutic approaches in AD.

PMID- 11239717
TI  - Plantar stimulation can affect subjective straight-ahead in neglect patients.
AB  - The rightward orientation bias of neglect patients has been shown to be decreased
      by postural changes, suggesting that afferences coding the posture relative to
      gravity might influence the body-centred spatial reference frame. In order to
      test this hypothesis, we evaluated the effects of plantar stimulations on the
      subjective straight-ahead (SSA) of two neglect patients presenting with a strong
      rightward shift, as well as two non-neglect patients and three normal subjects.
      Vibratory or electrical stimulations were applied to the left or right plantar
      sole. Data showed that these manipulations influenced the SSA position in neglect
      patients only. The observed improvement could be explained by a direction
      specific effect of vibration, in addition to a non-specific activation induced by
      both stimulations.

PMID- 11239718
TI  - Activation of CB1 cannabinoid receptors in rat hippocampal slices inhibits
      potassium-evoked cholecystokinin release, a possible mechanism contributing to
      the spatial memory defects produced by cannabinoids.
AB  - Cannabinoid use is known to disrupt learning and memory in a number of species.
      cholecystokinin (CCK) release and CCK receptors have been implicated in spatial
      memory processes in rodents. Rat hippocampal CCK interneurons express cannabinoid
      1 receptors (CB1). The CB1 agonist R(+)WIN 55,212-2 (WIN+), at 1 and 10 micromol,
      strongly inhibited potassium-evoked CCK release from rat hippocampal slices,
      while the inactive isomer S(-)WIN,55,212-3 (WIN-) had no effect. CCK release from
      cerebral cortical slices was not altered by WIN+.

PMID- 11239720
TI  - Feeling vibrations: enhanced tactile sensitivity in congenitally deaf humans.
AB  - The human nervous system displays remarkable functional plasticity following long
      term sensory deprivation. For example, the auditory cortex of congenitally deaf
      humans may start to process tactile information. To further explore this type of
      cross-modal plasticity, we examined the tactile accuracy of congenitally deaf and
      normal hearing subjects in frequency discrimination and in detection of random
      suprathreshold frequency changes within a monotonous sequence of vibratory
      stimuli. We found that congenital deafness can enhance the accuracy of
      suprathreshold tactile change detection while tactile frequency discrimination is
      not significantly changed, although there is a trend toward reduced thresholds.
      The enhanced tactile sensitivity in the deaf probably reflects both neural
      plasticity and increased attention directed to the stimuli. Whatever the
      underlying neural mechanisms might be, functional compensation following early
      sensory loss apparently leads the remaining sensory modalities to develop
      capacities exceeding those of the normal functional systems.

PMID- 11239719
TI  - Changes in cortical and hippocampal ectonucleotidase activities in mice lacking
      cellular prion protein.
AB  - Animals lacking cellular prion protein (PrP(c)) expression are more susceptible
      to seizures. Adenosine is an endogenous anticonvulsant agent and it levels in the
      synaptic cleft are regulated by ectonucleotidases. We evaluated ectonucleotidase
      activities in synaptosomes from hippocampus and cerebral cortex of adult PrP(c)
      null mice and wild-type mice (genetic background 129/Sv X C57BL/6J). There was an
      increase (47%) in adenosine triphosphate (ATP) hydrolysis in hippocampal
      synaptosomes of PrP(c) knockout mice as compared with the wild-type animals. In
      cortical synaptosomes, ATP hydrolysis was similar in both PrP(c) mice and
      controls. However, there was a significant decrease in adenosine diphosphate
      (ADP) hydrolysis in both hippocampal (-39%) and cortical (-25%) synaptosomes in
      PrP(c) null animals compared to wild-type mice. Changes in brain
      ectonucleotidases activities related to modifications in the PrP(c) expression
      may contribute, at least in part, to the higher sensitivity to seizures of PrP(c)
      null mice.

PMID- 11239722
TI  - Social reinforcement of substance abuse aftercare group therapy attendance.
AB  - Although adherence to aftercare therapy in substance abuse treatment is
      associated with improved treatment outcome, relatively little research has
      explored methods of improving aftercare adherence. To improve on established
      methods of promoting aftercare adherence, 43 graduates of the 28-day intensive
      substance abuse treatment program at the Salem Veteran's Affairs Medical Center
      who received standard aftercare orientation are compared to 38 graduates who
      received the standard intervention plus social reinforcement of aftercare group
      therapy attendance. Clients who received social reinforcement attended more
      aftercare group sessions than did clients who received the standard treatment
      during the 8-week intervention (68.8% vs. 49.4% of sessions attended), and during
      the 4-week follow-up period (41.5% vs. 31.4% of sessions). These findings are
      noteworthy since the standard treatment had been shown to be effective in
      increasing aftercare adherence in prior studies (Lash, 1998; Lash & Blosser,
      1999). Areas for future research are discussed.

PMID- 11239723
TI  - Substance abuse counselors' experiences with victims of incest.
AB  - Counselors delivering substance abuse treatment from within 39 treatment
      facilities throughout the United States were surveyed using the Substance Abuse
      Counselor Survey on Clients with Incest Histories (SACSCIH). The sample of 114
      participants reported upon experiences and perceptions related to their incest
      related training, identification of incest victims, prevalence of incest victims
      on their caseloads, and referral and treatment practices. Additionally, group
      comparisons provided information on differences based upon participants' gender,
      educational degree, recovery status, and experience with incest counseling.

PMID- 11239724
TI  - Relapse outcomes in a randomized trial of residential and day drug abuse
      treatment.
AB  - Relapse outcomes at 6-, 12-, and 18-month intervals were compared between clients
      randomly assigned to day (n=114) versus residential (n=147) drug abuse treatment.
      Day clients were more likely than residential clients to relapse 6 months post
      admission (OR=3.06, p<0.001); however, no setting differences at 12 or 18 months
      were found. Few baseline predictors were prospectively related to relapse at 12
      and 18 months. These predictors were usual employment status (part-time OR=17.47,
      p<0.001; full-time OR=2.54, p<0.001), history of drug injecting (OR=5.39,
      p<0.01), multiple sex partners (OR=1.16, p<0.01), and not having a gay sexual
      partner (OR=0.05, p<0.03) during 6 months prior to admission. Still, these
      baseline predictors, together with the existing literature, could be used by drug
      treatment professionals to identify individuals who may be at high risk for
      relapse over time, and to offer specialized treatment and aftercare resources as
      intervention and prevention measures.

PMID- 11239725
TI  - Self-help group participation among substance use disorder patients with
      posttraumatic stress disorder.
AB  - Debate has ensued about whether substance use disorder (SUD) patients with
      comorbid posttraumatic stress disorder (PTSD) participate in and benefit from 12
      step groups. One hundred fifty-nine SUD-PTSD and 1,429 SUD-only male patients
      were compared on participation in 12-step activities following an index episode
      of treatment. Twelve-step participation was similar for SUD patients with and
      without PTSD. PTSD patients with worldviews (e.g., holding disease model beliefs)
      that more closely matched 12-step philosophy participated more in 12-step
      activities. Although greater participation was associated with better concurrent
      functioning, participation did not prospectively predict outcomes after case mix
      adjustment. An exception was that greater participation predicted decreased
      distress among PTSD patients whose identity was more consistent with 12-step
      philosophy. In summary, PTSD patients participate in and benefit from 12-step
      participation; continuing involvement may be necessary to maintain positive
      benefits.

PMID- 11239726
TI  - Reinforcing compliance with non-drug-related activities.
AB  - Contingency management (CM) procedures, that provide incentives for specific
      behaviors, are efficacious in treating substance use disorders. Typically, CM
      interventions reinforce submission of urine specimens negative for the targeted
      drug(s) of abuse, but other behaviors can be reinforced as well, such as
      compliance with non-drug-related activities. This article describes 1,059
      activities chosen by 46 subjects participating in one of two CM studies. The most
      frequently chosen activities were related to recreational activities (going to
      movies, library, or church) and sobriety (attending Alcoholics Anonymous
      meetings, completing worksheets). Over 95% of subjects participated in at least
      one of these types of activities, and together they accounted for over 70% of the
      activities selected. Over half the subjects participated in at least one activity
      related to employment, health, family, and personal improvement, such as applying
      for a job, attending a medical appointment, taking their child to an event, or
      creating weekly to-do lists. A detailed description of activity selection and
      verification procedures may assist in developing consistent approaches across
      treatment settings, and future research may evaluate further the efficacy of this
      contingency management approach in treating substance abusers.

PMID- 11239727
TI  - Clinical profile of participants in a brief intervention program for cannabis use
      disorder.
AB  - The increasing demand for cannabis dependence treatment has led to the
      identification of significant gaps in the knowledge of effective interventions. A
      randomized controlled trial of brief cognitive-behavioral interventions (CBT) for
      cannabis dependence was undertaken to address this issue. A total of 229
      participants were assessed and allocated to either a 6-session CBT program, a
      single-session brief intervention, or a delayed-treatment control group. This
      paper demonstrates that individuals with cannabis use disorder will present for a
      brief intervention program. While they report similar patterns of cannabis use to
      nontreatment samples, they report a range of serious health and psychosocial
      consequences. While they appear relatively socially stable, they typically
      demonstrated severe cannabis dependence and significantly elevated levels of
      psychological distress, with the most commonly cited reason for cannabis use
      being stress relief. There were clinically relevant gender differences among the
      sample. This study provides more evidence of the demand for, and nature of issues
      relevant to, interventions for cannabis use disorders, and supports the need for
      further research into how best to assist individuals with these disorders.

PMID- 11239728
TI  - Gender differences in problem severity at assessment and treatment retention.
AB  - Women in treatment for substance abuse have been reported to have more severe
      problems at assessment than men but not to differ in treatment retention. To
      examine gender differences in problems at assessment, 30-day retention, and
      treatment completion, data from Detroit's publicly funded substance abuse
      treatment system were used. Women had significantly more severe problems at
      assessment, lower 30-day retention, and lower treatment completion rates than
      men. These gender differences in retention remained significant even after
      controlling for problem severity, primary drug of abuse, and referred treatment
      setting. There was no evidence of improvements in women's problems at assessment
      or retention over time during this period. Women presented with more severe
      problems at assessment and were less likely to stay in treatment for 30 days or
      to complete treatment than men. Monitoring gender differences in problems at
      presentation and retention outcomes is recommended to assess local need for
      interventions.

PMID- 11239729
TI  - Development of a skill training program for parents of substance-abusing
      adolescents.
AB  - This report discusses the development of a coping skill training program for
      parents of substance-abusing adolescents and presents preliminary data on the
      effects of the program on parent functioning and adolescent substance use. The
      behavioral-analytic model of program development was used to sample
      representative problematic situations experienced by parents of substance-abusing
      adolescents, obtain an effectiveness-scaling of responses to these situations,
      and derive alternate forms of a situational role-play measure of parental coping.
      These situations and scoring guidelines were then used to create the skill
      training program. Parents of substance-abusing adolescents not in treatment
      subsequently were randomly assigned in a pilot investigation to either a skill
      training or delayed treatment condition. Skill training resulted in significant
      improvement in parental coping skills relative to delayed treatment. Moderate to
      large improvement in the parent's report of their own functioning, family
      communication, and the teen's marijuana use also favored the skill training
      group.

PMID- 11239730
TI  - Positive by-products of the struggle with chemical dependency.
AB  - Focus groups were conducted to identify ways persons in recovery from chemical
      dependence think they have benefited from their struggles with addiction.
      Categories of positive by-products were identified independently by two sets of
      readers. Several of the positive by-products discussed by the focus group
      participants are commonly reported from other kinds of challenging life
      experiences. These include increases in self-efficacy, family closeness,
      closeness with others, compassion and spirituality, and changes in life
      priorities. Additional positive by-products were discussed by the focus group
      participants that may be more unique to substance abuse and other similar
      stressors, including increased self-knowledge, enhanced ability to help offspring
      with substance abuse-related issues, and decreased naivete. Ways to incorporate
      knowledge about these positive by-products into substance abuse treatment
      programs are introduced.

PMID- 11239731
TI  - The role of laboratory tests in alcoholism treatment.
AB  - Although assessment in the field of alcoholism treatment is generally verbal in
      nature, biological tests can also provide counselors and program evaluators
      useful and unique information. Five such laboratory measures are briefly
      described, with particular emphasis on carbohydrate deficient transferrin, a
      biomarker recently approved by the FDA. Applications for laboratory tests in
      alcohol screening, motivating patients, and monitoring treatment progress are
      also proposed.

PMID- 11239732
TI  - A commentary on "The role of laboratory tests for alcoholism treatment".

PMID- 11239733
TI  - Early findings from a disciplinary program to reduce problem drinking by college
      students.
AB  - This article describes an intervention for college students cited for alcohol
      related infractions of the student code of conduct. First-time offenders are
      required to attend a three-hour class that includes educational, attitudinal and
      skills-based activities. Students also complete self-report measures of
      quantity/frequency of consumption and are mailed personalized drinking feedback
      one week following the group session. A preliminary evaluation of the program is
      described and the intervention is discussed in relation to other programs
      available on campus.

PMID- 11239734
TI  - Reinforcement-based outpatient treatment for opiate and cocaine abusers.
AB  - A reinforcement-based intensive outpatient treatment was delivered to 37 recently
      detoxified, inner city, heroin and/or cocaine abusers who did not want methadone
      treatment. Attendance was scheduled and urine collected daily for the first 2
      weeks, four times weekly for the next 2 weeks, and then thrice weekly for the
      final 8 weeks. As attendance incentives, patients received transportation
      assistance (bus tokens), and $28-$30 per week in vouchers to be spent on
      activities/items chosen and agreed upon with their counselor. As abstinence
      incentives, patients received weekend supported recreational activities, lunches,
      $42-$45 per week in vouchers, and rent or utilities payment ($150 over 4 weeks).
      Total potential earnings was $1,435 per patient; actual mean earnings was $583.
      Forty-three percent (n=16) completed 10 or more weeks of treatment. These 16 long
      stay patients submitted 92% (SD=19) opiate- and cocaine-negative urines during
      their enrollment compared with 56% (SD=42) drug-negative urines submitted by 21
      drop-outs, F(1,35)=9.99, p=0.003. Overall, 32% of clients became employed during
      their treatment episode; 94% of long-stay patients were employed at the end of
      their treatment episode. Patients who were drug-positive at intake were highly
      likely to drop out. Treatment outcomes compare favorably with those reported in
      the literature for outpatient nonmethadone treatment of opiate and cocaine
      abusers. Continued evaluation of this new treatment appears warranted.

PMID- 11239735
TI  - Reducing resistance and denial by exercising ambivalence during the treatment of
      addiction.
AB  - Stage change models and motivational enhancement therapies have significantly
      influenced the therapeutic tactics clinicians employ in the treatment of
      addictive behaviors. While motivational enhancement strategies have addressed
      client ambivalence to increase motivation to change, this article suggests that
      focusing on ambivalence during treatment has even wider clinical utility than
      previously thought. Resistance reduction concentrates on exercising ambivalence
      without an investment in clients changing, thereby strengthening client tolerance
      for ambivalent thoughts and feelings. Exercising ambivalence reduces resistance
      to treatment and change by validating a wide array of possible outcomes through
      detailed exploration of how a behavior pattern works for a client. Since
      resistance reduction does not require clients to want to change for therapy to
      progress, exploring the decision-making process becomes paramount. A general
      discussion of the resistance reduction model, ambivalence, and how clients
      present for treatment precedes clinical case examples.

PMID- 11239736
TI  - Quality of life assessment and outcome of palliative care.
AB  - Quality of life (QoL) assessment is crucial for the evaluation of palliative care
      outcome. In this paper, our methodological approach was based on the creation of
      summary measures. Fifty-eight Palliative Care Units (PCUs) in Italy participated
      in the study. Each PCU randomly selected patients to be 'evaluated' among the
      consecutively 'registered' patients. At baseline (first visit) and each week the
      patient was asked to fill in a QoL questionnaire, the Therapy Impact
      Questionnaire (TIQ). Short-survivors (<7 days) were not included in the QoL
      study. The random sample of patients (n = 601) was highly representative of the
      general patient population cared for by the PCUs in Italy. The median survival
      was 37.9 days. We collected 3546 TIQ, 71.4 % completed by the patients. A Summary
      Measure Outcome score was calculated for 409 patients (81% of the patients
      included in the QoL study). The results of this national study showed that
      cooperative clinical research in palliative care is possible and QoL measures can
      be used to assess the outcome.

PMID- 11239737
TI  - Does the medical record cover the symptoms experienced by cancer patients
      receiving palliative care? A comparison of the record and patient self-rating.
AB  - The aim of this study was to investigate the extent to which the symptoms
      experienced by advanced cancer patients were covered by the medical records.
      Fifty-eight patients participated in the study. On the day of first encounter
      with our palliative care department, a medical history was taken, and on this or
      the following day, the patients completed the EORTC Quality of Life Questionnaire
      (EORTC QLQ-C30), Edmonton Symptom Assessment System (ESAS), and Hospital Anxiety
      and Depression Scale (HADS). The symptomatology reported in the patient-completed
      questionnaires was compared with the symptomatology mentioned by the physician in
      the medical record. The analysis revealed good concordance concerning pain, but
      most other symptoms or problems were reported much more often by patients than by
      their doctors. Reasons for these discrepancies are discussed. It is suggested
      that the doctor's knowledge of the patient's symptomatology might gain from more
      systematic screening and transfer of information from patient self-assessment
      questionnaires to the medical records.

PMID- 11239738
TI  - Differences between patients referred to hospice from academic vs. non-academic
      settings.
AB  - Hospice is designed to provide end-of-life care to patients who are terminally
      ill. Increasingly, hospices are developing affiliations with academic medical
      centers. However, little is known about this group of patients, and how their
      needs may differ from those of the general population of hospice patients. To
      identify differences between patients referred to an urban, non-profit hospice
      from academic vs. non-academic medical centers, a retrospective cohort study of
      1,691 patients admitted to an inpatient and outpatient hospice program was
      conducted. Admission dates were between January 1997 and January 1999, and data
      were gathered until discharge or death. The major outcome of interest was the
      need for nursing interventions at the time of entry into hospice. Patients
      referred from academic medical centers were younger, had higher incomes, and were
      less likely to have Medicare or Medicaid. Patients referred from academic medical
      centers were less likely to have a Do Not Resuscitate order or a living will, and
      had more medical and nursing needs. Survival analysis revealed no difference in
      length of stay between patients referred from academic and non-academic medical
      centers. Patients referred to hospice from academic medical centers have greater
      needs for nursing and medical care than do patients referred from non-academic
      medical centers. The implications of these findings for policy are discussed.

PMID- 11239739
TI  - A phase II study to establish the efficacy and toxicity of sodium valproate in
      patients with cancer-related neuropathic pain.
AB  - The efficacy and toxicity of sodium valproate for cancer-related neuropathic pain
      was evaluated in a phase II study at this cancer center. Twenty-five patients
      entered the study over a 13 month period. Pain was assessed using a pain scale
      based on the Brief Pain Inventory at days 0, 8 and 15. Nineteen patients
      completed the two week study period, one patient discontinued treatment because
      of toxicity, and five discontinued because of progressive disease. The most
      frequently observed side effects were drowsiness, unsteadiness, nausea, and
      decreased appetite. Response was defined as a decrease in pain score in the
      absence of increased need for analgesic medication. The response rate for average
      pain at day 15 in assessable patients was 55.6% (30.8-78.5%, 95% CI), but
      response rates varied considerably depending on the mode of analysis. Baseline
      efficacy data have been gained on which to base future comparative studies
      against antidepressants.

PMID- 11239741
TI  - Pain management program follow-ups. a national survey of current practice in the
      United Kingdom.
AB  - In the United Kingdom (UK), the number of multidisciplinary pain management
      programs (PMP) has sharply increased in the last decade. Treatment aims to effect
      long-term changes, yet arrangements for evaluating long-term treatment outcome in
      routine practice remain unknown. All PMPs identified in the UK were invited to
      provide information by mailed questionnaire on aspects of follow-up evaluation.
      Sixty-six of 70 PMPs identified were successfully contacted (94% response rate).
      Ten of 48 PMPs (21%) provided complete data and met suggested criteria for
      adequate length and rates of follow-up, and outcome measurement. Levels of
      staffing and content explained only a proportion of the variability seen. A
      general commitment to follow-up outcome evaluation by PMPs was identified but
      there was substantial variability among programs in length of follow-up,
      attendance rates, and outcome measurement. These findings raise issues about the
      consistency of follow-up evaluation across the UK and the ability of current
      arrangements in some PMPs to accurately determine the longer-term outcome of
      chronic pain patients. Incorporating follow-ups into existing desirable criteria
      and agreeing on core outcome measures are two options available to service
      providers.

PMID- 11239740
TI  - Impact of experimentally-induced expectancy on the analgesic efficacy of tramadol
      in chronic pain patients: a 2 x 2 factorial, randomized, placebo-controlled,
      double-blind trial.
AB  - Variations in treatment effects between drug trials are usually attributed to
      different patient characteristics, variations in outcome assessment, and random
      error. We have previously hypothesized that part of the variation in treatment
      effects between drug trials might be caused by differences in nonspecific
      factors. In a randomized clinical trial, we aimed to investigate whether
      experimentally induced expectancy can modify the analgesic effect of tramadol
      relative to placebo in chronic pain patients. In a 2 x 2 factorial, randomized,
      placebo-controlled, double-blind trial, chronic pain patients attending a chronic
      pain outpatient clinic were randomized to receive a single oral dose of 50 mg
      tramadol or placebo, and they were further randomized to receive positive or
      neutral information, verbally expressed by the physician, regarding the expected
      analgesic effect of the drug. Pain intensity was measured using a 10 centimeter
      visual analogue scale at baseline, and 0.5, 1, 2, 4, 6, and 8 hours after
      baseline. The one-hour pain intensity difference, calculated as the sum of pain
      intensity differences between baseline and 0.5 and 1 hour, was taken as main
      outcome measure. The one-hour sum of pain intensity differences of 28 patients
      treated after positive expectation and randomized to tramadol was 1.4 cm, while
      in 27 patients randomized to placebo, it was 0.8 cm. This corresponds with an
      analgesic effect of tramadol relative to placebo of 0.6 cm (95% confidence
      interval [CI], -0.5 cm to 1.8 cm). The 28 patients in the neutral expectancy
      group who were randomized to tramadol reported a 1.4 cm decrease on the sum of
      pain intensity differences, while 28 patients in the placebo group reported a 0.9
      cm decrease. This corresponds with an analgesic effect of tramadol relative to
      placebo of 0.5 cm (95% CI, -0.9 cm to 1.8 cm). The 0.1 cm difference (0.6 cm -
      0.5 cm) in analgesic effect between positive and neutral expectancy group was not
      statistically significant (95% CI, -0.7 cm to 1.0 cm). This trial did not discern
      a significant difference in the analgesic effect of tramadol between a positive
      and neutral expectancy group. This means that the phenomenon either does not
      exist, or we had an inappropriate model to demonstrate it. Regardless, this study
      demonstrates the type of quality trial that should be done to find out which non
      specific factors, such as information regarding the expected effect, can modify
      treatment effects.

PMID- 11239742
TI  - Controlled substances and pain management: changes in knowledge and attitudes of
      state medical regulators.
AB  - Physicians report that concern about regulatory investigation negatively
      influences their prescribing of opioid analgesics. The views of medical
      regulators about the legality of prescribing controlled substances for pain
      management were studied in 1991. However, little is known about whether these
      views have changed in light of increased emphasis on pain management and
      educational programs for state medical boards. Two studies that examined this
      issue are described. In Study 1, a 1997 survey of state medical board members was
      compared to results obtained in 1991 to evaluate differences in knowledge and
      perceptions about opioid analgesics. Important changes were observed over time,
      particularly regarding characteristics of "addiction" and the legality of
      prolonged prescribing of opioids. For Study 2, a longitudinal survey was
      conducted of medical board members who participated in five workshops about pain
      management and regulatory policy. Results revealed significant and sustained
      changes in attitudes about the incidence of iatrogenic addiction when using
      opioids to treat pain, the analgesic and side-effect properties of opioids, and
      the perceived legality of prescribing opioids. Recommendations for reducing
      concerns about regulatory scrutiny are presented, including the need for a more
      intensive education program, increasing the rate of adoption of new state medical
      board policies, and improving communication between regulators and clinicians.

PMID- 11239743
TI  - Prospective investigations into the safety of spinal manipulation.
AB  - Spinal manipulation (SM) is a popular form of treatment of back and neck pain, as
      well as of other conditions. Uncertainty exists as to its safety. The aim of this
      systematic review was to summarize the data of all prospective investigations
      into the safety of SM. Five independent literature searches were carried out to
      identify all such studies. Data were extracted and validated according to pre
      defined criteria. Five investigations met the inclusion criteria. The most valid
      studies suggest that about half of all patients will experience adverse events
      after chiropractic SM. These events are usually mild and transient. No reliable
      data exist about the incidence of serious adverse events. These data indicate
      that mild and transient adverse events seem to be frequent. Serious adverse
      events are probably rare but their incidence can only be estimated at present.
      Further prospective investigations are needed to define their incidence more
      closely.

PMID- 11239744
TI  - Liza's death: a personal recollection.

PMID- 11239745
TI  - Improving end-of-life care: listening to voices from the trenches.

PMID- 11239746
TI  - Learning from Liza.

PMID- 11239747
TI  - A child's legacy.

PMID- 11239748
TI  - Opioid poorly-responsive cancer pain. Part 2: basic mechanisms that could shift
      dose response for analgesia.
AB  - Basic research in experimental pain models may illuminate the phenomenon of
      cancer pain that is poorly responsive to opioid drugs. Research findings can be
      valuable in formulating new strategies in clinical practice. This review
      evaluated experimental observations in terms of the events that occur in cancer
      patients receiving opioid therapy for pain.

PMID- 11239750
TI  - Abstracts of the 2nd European College of Neuropsychopharmacology workshop. Nice,
      France, March 15-18, 2001.

PMID- 11239751
TI  - Can improved communication increase patient participation in randomised clinical
      trials?

PMID- 11239752
TI  - Germ line mutations associated with breast cancer susceptibility.
AB  - Laboratory-based research in germ line mutations associated with breast cancer
      susceptibility is rapidly being integrated into clinical practice with profound
      implications. A Medline search was performed for all relevant articles published
      since 1990. Where appropriate, historical articles referenced in those identified
      were also reviewed. The results suggested that while mutations in the BRCA1 and
      BRCA2 genes are the most clinically relevant, much of the data on which clinical
      decisions are based must be interpreted with wide confidence intervals. Between 1
      in 152 and 1 in 833 individuals carry such mutations. They account for less than
      5% of all breast cancer, but up to 10% of cancers in those under the age of 40
      years. Founder mutations are responsible for a larger proportion of breast cancer
      cases within certain inbred communities. Phenotypic expression and penetrance of
      different mutations is not currently predictable and estimates of penetrance are
      largely based on highly selected populations. BRCA1 mutations are more commonly
      associated with ovarian cancer than BRCA2 mutations. BRCA1 cancers tend to have
      more distinct pathological features and are usually oestrogen receptor (ER)
      negative. To conclude, the evidence in this review suggests that caution should
      be exercised when translating scientific progress in breast cancer germ line
      genetics into clinical practice. Most of the available data are derived from
      studies on highly selected populations. The importance of other less penetrant,
      but more prevalent, germ line mutations may be realised in the future.

PMID- 11239753
TI  - Results of an intervention study to improve communication about randomised
      clinical trials of cancer therapy.
AB  - We report results from an intervention study to improve communication during
      consultations about randomised clinical trials of cancer therapy. Patients,
      eligible for a trial, completed questionnaires about information preferences and
      attitudes to trials prior to seeing their doctors, who were either shown these
      questionnaires (intervention) or not (control). Fifteen doctors participated and
      invited 265 patients to join one of 40 different randomised clinical trials. Most
      patients (77.4%) agreed to trial entry and this was predicted by the Patient's
      Attitudes to Trials questionnaire with an 80.4% accuracy. Accrual, length of
      consultation, doctor and patient satisfaction were not associated with the
      intervention. Further research to explore the potential use of written
      interventions to facilitate communication and accrual to randomised clinical
      trials is recommended.

PMID- 11239754
TI  - Sociodemographic factors and quality of life as prognostic indicators in head and
      neck cancer.
AB  - Pre-treatment quality of life (QOL) has been found to be an independent
      prognostic factor for survival in cancer patients, in particular in patients with
      advanced cancer. Sociodemographic factors such as marital and socioeconomic
      status have also been recognised as prognostic factors. We studied the influence
      of QOL and mood (measured with the European Organization for Research and
      Treatment of Cancer Core Questionnaire (EORTC QLQ-C30) and the Head and Neck
      Cancer Questionnaire (EORTC QLQ-H&N35), and with the Center for Epidemiologic
      Studies-Depression Scale (CES-D)) as measured before treatment, the use of
      cigarettes and alcohol and sociodemographic factors (age, gender, marital status,
      income and occupation) on recurrence and survival in 208 patients with head and
      neck cancer prior to treatment with surgery and/or radiotherapy, using Kaplan
      Meier and Cox regression analyses. Cognitive functioning and, to a lesser degree,
      marital status were independent predictors of recurrence and survival, along with
      medical factors (stage and radicality). Patients with less than optimal cognitive
      functioning and unmarried patients had a relative risk (RR) of recurrence of 1.72
      (95% confidence interval (95% CI) 1.01-2.93) and 1.85 (95% CI 1.06-3.33),
      respectively, and a RR of dying of 1.90 (95% CI 1.10-3.26) and 1.82 (95% CI 1.03
      3.23), respectively. Performance status, physical functioning, mood and global
      QOL and smoking and drinking did not predict for recurrence and survival. The
      influence of cognitive functioning might be related to the use of alcohol.
      Marital status may influence prognosis through mechanisms of health behaviour
      and/or social support mechanisms.

PMID- 11239755
TI  - Genetic changes of hOGG1 and the activity of oh8Gua glycosylase in colon cancer.
AB  - oh8Gua glycosylase repairs DNA by removing oh8Gua, a highly mutagenic oxidative
      DNA adduct. Recently, the gene for human oh8Gua glycosylase (hOGG1) was cloned
      and several mutational types have been reported. However, the implications of
      such mutations in human cancer have not been clearly demonstrated. To test the
      involvement of hOGG1 mutation in colon carcinogenesis, we analysed the genetic
      changes of hOGG1 and the activity of oh8Gua glycosylase in 15 paired normal and
      tumorous colon specimens. The activity of antioxidant enzymes (catalase and
      superoxide dismutase (SOD)) and extent of oxidative cellular damage (oh8Gua and
      malondialdehyde) were also assessed to compare the oxidative status of normal and
      tumour tissues. An Arg 154 to His mutation was detected in two tumour samples,
      but not in the corresponding normal tissues. A Ser 326 to Cys mutation
      (polymorphism) was found in both the normal and tumour tissues of 3 patients.
      However, neither the Arg 154 to His mutation nor the polymorphism at codon 326
      significantly decreased the oh8Gua glycosylase activity. The mean activity of
      oh8Gua glycosylase was significantly higher in the tumours than in normal tissues
      (P=0.022). Antioxidant enzyme activities were decreased (catalase; P=0.004 and
      SOD; P=0.002), and the extent of oxidative damage correspondingly increased in
      the tumour tissues (oh8Gua; P=0.007 and malondialdehyde; P=0.046). Although the
      sample size was limited, these results suggest that the somatic mutation or the
      polymorphism of hOGG1 is less likely to be involved in colon carcinogenesis.
      Nevertheless, the greater oxidative DNA damage in the tumour tissues, as a
      possible result of impaired antioxidant activity, implies an important role for
      oxygen free-radicals in colon carcinogenesis.

PMID- 11239756
TI  - c-erbB-2 positivity is a factor for poor prognosis in breast cancer and poor
      response to hormonal or chemotherapy treatment in advanced disease.
AB  - The aim of this work was to evaluate the prognostic and predictive values of c
      erbB-2 in breast cancer. 650 patients were enrolled. The
      amplification/overexpression of c-erbB-2 from fresh frozen or paraffin-embedded
      breast tumour tissue samples was analysed by polymerase chain reaction (PCR)
      technique (75%), immunohistochemically (17%) or by Southern blot analysis (8%).
      126 patients (19%) were positive for c-erbB-2. 148 patients developed metastatic
      disease, but only 35 were positive for c-erbB-2. Positivity for c-erbB-2 was
      significantly associated with node positivity, large tumour size, high grade of
      malignancy, low receptor status, postmenopausal status, and with a shorter
      overall survival. In multivariate regression analysis, only tumour size and nodal
      involvement were risk factors for poor survival when analysed separately together
      with c-erbB-2 and receptor status. Metastatic patients with c-erbB-2 positivity
      had a significantly shorter survival and disease-free survival (DFS) than the c
      erbB-2-negative patients. 29 advanced patients with c-erbB-2 positivity showed a
      poor response rate to hormonal, non-anthracycline-based and anthracycline-based
      therapies. Positivity for the c-erbB-2 is a poor prognostic factor in breast
      cancer, but it also emerges as predictive of the response to hormonal or
      chemotherapy treatment once the disease has recurred.

PMID- 11239757
TI  - CA27.29: a valuable marker for breast cancer management. A confirmatory
      multicentric study on 603 cases.
AB  - Recently, a fully automated method has become commercially available to measure
      the MUC-1-associated antigen CA27.29. The present investigation was performed in
      order to compare CA27.29 and CA15.3 in a wide series of patients affected with
      breast cancer. Overall, 603 cases with breast cancer and 194 healthy controls
      were investigated. Patients were enrolled in 4 institutions, while assays were
      performed in one laboratory. CA27.29 was measured by the ACS:180 BR assay (Bayer
      Diagnostics) and CA15.3 by the AxSYM (Abbott Laboratories). An excellent
      correlation was found between the results obtained by the two methods. The two
      markers showed comparable results in healthy controls, with higher levels in post
      menopausal than in pre-menopausal subjects. The markers were significantly higher
      in primary breast cancer than in controls. The areas under the receiver operating
      characteristics (ROC) curves of the two tests were comparable, but CA27.29 showed
      better sensitivity in cases with low antigen concentrations (below the cut-off
      point). Accordingly, when comparing each test in different stage categories,
      significance levels of the differences were higher for CA27.29 than for CA15.3
      for all T categories versus healthy controls, for pT1 versus pT2, for all N
      categories versus healthy controls and for node-negative versus N1-3 patients.
      From the results of the present study, that has been performed on samples taken
      at diagnosis and prior to any treatment from the widest series of patients with
      primary breast cancer reported so far, we can draw the following conclusions:
      CA27.29 provides comparable results to CA15.3; CA27.29 seems more sensitive than
      CA15.3 to limited variations of tumour extension; however, it cannot help
      clinicians in distinguishing stage I patients from stage II patients. However,
      from the point of view of clinical decision making, CA27.29 provides comparable
      results to CA15.3. CA27.29 is therefore suitable for routine use in the
      management of patients with breast cancer.

PMID- 11239758
TI  - Paclitaxel, cisplatin and lonidamine in advanced ovarian cancer. A phase II
      study.
AB  - A potential way to improve the results obtained with the standard
      carboplatin/cisplatin (CDDP)-paclitaxel treatment regimen in advanced ovarian
      cancer is to incorporate a modulating agent such as lonidamine (LND). In fact,
      LND has been shown to revert the resistance to cisplatin and to potentiate
      cisplatin activity experimental models and in clinical studies. 35 consecutive
      patients with advanced ovarian cancer, not previously treated with chemotherapy
      were treated with paclitaxel at a dose of 135 mg/m(2) intravenously (i.v.) on day
      1 (in a 3 h infusion) and cisplatin at a dose of 75 mg/m(2) iv on day 2 plus LND
      orally (p.o.) at a dose of 450 mg/die for 6 consecutive days starting two days
      before chemotherapy, every 3 weeks for six cycles. Complete plus partial
      responses were observed in 8 (80%) out of the 10 women with measurable disease.
      In the 25 patients with evaluable disease, only four clinical progressions were
      observed (16%). Median progression-free survival (PFS) and overall survival (OS)
      were 28.5 (95% confidence interval (CI) 22.2-34.8) and 46.5 (95% CI 32.4-60.00)
      months respectively. Grade 3-4 neutropenia was observed in 9 (26%) patients.
      Alopecia, nausea and vomiting (Grade 3) were observed in 33 (94%) and 5 (14%)
      patients, respectively. In conclusion, the combination of CDDP/paclitaxel plus
      LND is active and tolerable in the treatment of advanced ovarian cancer.

PMID- 11239759
TI  - Economic analysis of adjuvant therapy with interferon alpha-2a in stage II
      malignant melanoma.
AB  - Using the trial demonstrating that interferonalpha-2a (IFNalpha-2a) is
      efficacious as adjuvant therapy in stage II melanoma, we evaluate its outcomes
      and economic consequences. Using rates observed in the 5-year trial and published
      figures, survival and Q-TWIST (Time Without Symptoms and Toxicity) were
      extrapolated to a 10-year and lifetime horizon. Cost analysis was performed using
      the trial's data, published literature and experts' opinions from the perspective
      of the French Sickness Funds. Patients in the IFNalpha-2a-group have an
      additional 0.26 years in life-expectancy over a 5-year time period (P=0.046),
      0.67 years over a 10-year period and 2.59 years over a lifetime. Cost per life
      year-gained was estimated at approximately 14400 after 5 years, 6635 after 10
      years and 1716 over a lifetime. Assuming that there is an improvement in disease
      free survival only, cost is 26147 per Q-TWIST. Cost-effectiveness of IFNalpha-2a
      in stage II melanoma compares favourably with estimates for widely used therapies
      in the oncological field.

PMID- 11239760
TI  - Predicting anxiety and depression among cancer patients: a clinical model.
AB  - The aim of this study was to investigate the possibility of predicting anxiety
      and depression 6 months after the cancer diagnosis on the basis of measures of
      anxiety, depression (Hospital Anxiety and Depression, HAD scale), subjective
      distress (Impact of Event, IES scale) and some aspects of social support in
      connection with the diagnosis. A further purpose was to attempt identification of
      individual patients at risk of prolonged psychological distress, and to develop
      an easily applicable clinical tool for such detection. A consecutive population
      based series of 522 newly diagnosed patients with breast, colorectal, gastric and
      prostate cancer were interviewed in connection with the diagnosis and 6 months
      later. Anxiety and depression close to the diagnosis explained 39% of the
      variance in anxiety and depression 6 months later. Patients scoring as doubtful
      cases/cases for HAD anxiety and/or depression were more than 11 times more likely
      than non-cases to score as doubtful cases/cases at 6 months. Additional risk
      factors were having an advanced disease and nobody in addition to the family to
      rely on in case of difficulties. Levels of anxiety and depression at diagnosis
      predict a similar status 6 months later. The results also indicate that the HAD
      scale in combination with a single question about social support may be a
      suitable screening tool for clinical use.

PMID- 11239761
TI  - Does nephroblastomatosis influence the natural history and relapse rate in Wilms'
      tumour? A single centre experience over 11 years.
AB  - The presence of multifocal or diffuse nephrogenic rests (NRs) in one or both
      kidneys is termed nephroblastomatosis (Nbm). Nbm may be a predisposing factor for
      Wilms' tumour (WT). The aim of this retrospective study was to evaluate the
      impact of Nbm on the outcome of WT in children. We assessed the outcome of 81
      children with Wilms tumours and practical implications of Nbm in the treatment
      and follow-up. All the pathology slides have been reviewed in 1997. 63 had WT
      without Nbm (group A) and 18 had WT associated with Nbm (group B). There was no
      statistical difference between the two groups according to the age at diagnosis
      and histology. Clinical abnormalities were more frequent in group B (33 versus
      8%). There was no statistical difference between the percentage of stage IV in
      both groups, but bilaterality (stage V) was present only in the group B. Relapse
      was observed in 20/81 patients (25%): 11 (17%) in group A and 9 (50%) in group B.
      Mean delay of relapse was longer (25 months) in group B than in group A (10
      months). For the whole population, with a median follow-up of 9 years, the event
      free survival (EFS) and the overall survival (OS) probabilities were respectively
      74%+/-10 and 83%+/-9 at 120 months. The difference in EFS between groups A (82+/
      9%) and B (38%+/-29) was significant (P=0.004). The discovery of Nbm in the non
      tumoral part of the kidney with WT can be an adverse factor and in particular
      favours the subsequent development of a new Wilms tumour. It justifies separate
      follow-up guidelines.

PMID- 11239762
TI  - Are alcohol intake and smoking associated with mycosis fungoides? A European
      multicentre case-control study.
AB  - The incidence of mycosis fungoides (MF) is low, and the aetiology of the disease
      is unknown. The aim of this study was to investigate whether wine consumption
      protects against the disease and whether smoking constitutes a risk factor. This
      paper is part of the European Rare Cancers Study that tries to determine the risk
      factors for seven selective rare cancers, including mycosis fungoides, involved
      in the development of cancer. A multicentre case-control study was conducted in
      six European countries. Only incident cases with confirmed histology were
      included in the analysis which include a total of 76 cases of MF and 2899
      controls. Wine intake had no protective effect; on the contrary the consumption
      of more than 24 g of alcohol per day was associated with a high risk of MF (odds
      ratio (OR)=3.02, 95% confidence interval (CI), 1.34-6.79), after adjusting for
      centre, country, age, sex and education. There was a dose-dependent increase in
      the risk of MF with increased smoking habits, albeit the observed trend was not
      statistically significant. A combined exposure to high tobacco and alcohol use
      yielded a significantly increased risk factor for MF (P=0.0073). Alcohol intake
      was associated with MF.

PMID- 11239763
TI  - Evaluation of the optimum cut-off point in immunochemical occult blood testing in
      screening for colorectal cancer.
AB  - This study was carried out to assess, from the aspects of cost-effectiveness and
      diagnostic validity, the optimum cut-off point for immunochemical occult blood
      testing using a 2-day method as a means of screening for colorectal cancer. Four
      thousand, two hundred and sixty asymptomatic individuals were subjects of this
      study. They gave samples for an immunochemical fecal occult blood test, and
      colonoscopy was carried out during a medical check-up. For evaluation of the
      optimum cut-off point, three cut-off levels of fecal haemoglobin, 50, 150 and 300
      ng/ml, were used. A total of 27 patients with colorectal cancer were diagnosed.
      The average costs to detect one patient with colorectal cancer and the
      sensitivity and specificity of these three cut-off points of fecal haemoglobin
      were evaluated. The average costs for the detection of one cancer case were
      calculated as $2870.45 for cut-off level of 50 ng/ml, $2492.98 for that of 150
      ng/ml and $3329.09 for that of 300 ng/ml, respectively. The sensitivity and
      specificity were calculated as 89 and 94% for the 50 ng/ml cut-off level, 81% and
      96% for the 150 ng/ml cut-off level and 56 and 97% for the 300 ng/ml cut-off
      level, respectively, indicating a significant difference in the sensitivity
      between the 50 and 300 ng/ml levels (P<0.05), as well as between the 150 and 300
      ng/ml levels (P<0.05), and a significant difference in the specificity between
      the 50 and 300 ng/ml levels (P<0.05). However, no significant difference was
      observed in the specificity between the 50 and 150 ng/ml levels. The findings
      show that 150 ng/ml of fecal haemoglobin is the optimal cut-off point when
      carrying out the OC-Hemodia test as a means of screening for colorectal cancer.

PMID- 11239765
TI  - Effects of electrochemotherapy with bleomycin on normal liver tissue in a rat
      model.
AB  - Preliminary studies that used electric pulses in vivo to facilitate entry of
      chemotherapeutic agents into tumour cells resulted in a 69% complete response
      rate for hepatocellular carcinoma in rats. This success motivated a focused
      investigation to define the adverse effects of this treatment on normal liver
      tissue. Bleomycin doses ranging from 0.5 to 2.5 U and electric fields from 500 to
      2250 V/cm were investigated. Electrical treatment was administered using an array
      of six needles arranged in a circular pattern. Necrosis and four other
      histological parameters were examined 14 and 56 days after treatment. Results
      indicated that treatment effects were localised to the volume of treated tissue.
      These parameters, at both time points, were not significantly altered for liver
      tissue that was treated with all drug doses and electric fields of 1250 V/cm and
      below. Only the combination of more intense electric pulses with bleomycin
      produced adverse histological events in the form of localised liver necrosis at
      day 14. These effects were not visible at day 56. Liver function was normal
      through all of the treatment except for an elevation of several enzymes 1 day
      post-treatment.

PMID- 11239764
TI  - Effects of gamma-linolenic acid and oleic acid on paclitaxel cytotoxicity in
      human breast cancer cells.
AB  - It has been suggested that dietary interventions may improve the effectiveness of
      cancer chemotherapy. We have examined the combined in vitro cytotoxicity of
      paclitaxel and the fatty acids gamma-linolenic acid (GLA, 18:3n-6) and oleic acid
      (OA, 18:1n-9) in human breast carcinoma MDA-MB-231 cells. The effect of fatty
      acids on paclitaxel chemosensitivity was determined by comparing IC(50) and
      IC(70) (50 and 70% inhibitory concentrations, respectively) obtained when the
      cells were exposed to IC(50) and IC(70) levels of paclitaxel alone and fatty
      acids were supplemented either before or during the exposure to paclitaxel. The 3
      4,5-dimethylthiazol-2-yl-2,5-diphenyl-tetrazolium bromide (MTT) assay was used to
      determine cell growth inhibition. GLA by itself showed antiproliferative effects,
      and a possible GLA-paclitaxel interaction at the cellular level was assessed by
      the isobologram and the combination-index (CI) methods. Isobole analysis at the
      isoeffect levels of 50 and 70% revealed that drug interaction was predominantly
      synergistic when GLA and paclitaxel were added concurrently for 24 h to the cell
      cultures. Interaction assessment using the median-effect principle and the
      combination-index (CI) method showed that exposure of MDA-MB-231 cells to an
      equimolar combination of concurrent GLA plus paclitaxel for 24 h resulted in a
      moderate synergism at all effect levels, consistent with the results of the
      isobologram analysis. When exposure to GLA (24 h) was followed sequentially by
      paclitaxel (24 h) only an additive effect was observed. The GLA-mediated increase
      in paclitaxel chemosensitivity was only partially abolished by Vitamin E, a lipid
      peroxidation inhibitor, suggesting a limited influence of the oxidative status of
      GLA in achieving potentiation of paclitaxel toxicity. When OA (a non
      peroxidisable fatty acid) was combined with paclitaxel, an enhancement of
      chemosensitivity was found when OA was used concurrently with paclitaxel,
      although less markedly than with GLA. Pretreatment of MDA-MB-231 cells with OA
      for 24 h prior to a 24 h paclitaxel exposure produced greater enhancement of
      paclitaxel sensitivity at high OA concentrations than the concurrent exposure to
      OA and paclitaxel. The OA-induced sensitisation to paclitaxel was not due to the
      cytoxicity of the fatty acid itself. When these observations were extended to
      three additional breast carcinoma cell lines (SK-Br3, T47D and MCF-7),
      simultaneous exposure to GLA and paclitaxel also resulted in synergism. GLA
      preincubation followed by paclitaxel resulted in additivity for all cell lines.
      Simultaneous exposure to paclitaxel and OA enhanced paclitaxel cytotoxicity in
      T47D and MCF-7 cells, but not in SK-Br3 cells, whereas preincubation with OA
      failed to increase paclitaxel effectiveness in all three cell lines. For
      comparison, the effects of other fatty acids on paclitaxel chemosensitivity were
      examined: GLA was the most potent at enhancing paclitaxel cytotoxicity, followed
      by alpha-linolenic acid (ALA; 18:3n.3), eicosapentaenoic acid (EPA; 20:5n-3) and
      docosahexaenoic acid (DHA; 22:6n-3), whereas linoleic acid (LA; 18:2n-6) did not
      increase paclitaxel toxicity. These findings provide experimental support for the
      use of fatty acids as modulators of tumour cell chemosensitivity in paclitaxel
      based therapy.

PMID- 11239766
TI  - Treatment of hepatocellular carcinoma in a rat model using electrochemotherapy.
AB  - The effectiveness of antineoplastic agents has been augmented by applying pulsed
      electric fields directly to tumours after the administration of the drug. This
      treatment, known as electrochemotherapy (ECT), has been successful for cutaneous
      malignancies in animal models and in recent clinical trials. This study was aimed
      at investigating the applicability of ECT in a surgical setting for
      hepatocellular carcinomas induced in the livers of rats. Established tumours were
      injected with bleomycin, and electric pulses were then administered locally.
      Animals were followed based on tumour volumes and histological samples. Dose
      response data were obtained for both electric field intensity and bleomycin.
      Complete response rates for animals treated with electrochemotherapy ranged from
      26.67% to 93.33 and were durable. In contrast, tumours that received no
      treatment, pulses only or drug only responded minimally. This supports the
      feasibility of using a ECT as a modality for treating hepatocellular carcinoma.

PMID- 11239767
TI  - Tissue distribution, antitumour activity and in vivo apoptosis induction by
      MEN10755 in nude mice.
AB  - MEN10755 is a disaccharide analogue of doxorubicin (DXR) endowed with a broader
      spectrum of activity compared with DXR in a panel of human tumour xenografts. In
      an attempt to investigate the pharmacological basis of the improvement of
      therapeutic efficacy of the analogue, a comparative pharmacokinetic (tissue and
      tumour distribution) and pharmacodynamic (antitumoral activity and ability to
      induce apoptosis) study of MEN10755 and DXR was performed in athymic nude mice
      bearing a human ovarian carcinoma xenograft (A2780). Drug level was quantified by
      high performance liquid chromatography (HPLC) with fluorimetric detection after a
      single intravenous (i.v.) injection of 7 mg/kg of MEN10755 or DXR. The results
      indicated a reduced accumulation of MEN10755 compared with DXR in all tissues
      investigated (tumour, heart, kidney and liver). The reduction was more marked in
      normal than tumour tissues. Moreover, in spite of the reduced drug uptake by
      tumour tissues, the new disaccharide anthracycline given in its optimal regimen
      showed an enhanced antitumour efficacy, compared with DXR. The drug effects on
      tumour growth paralleled a marked activation of apoptosis. In conclusion, the
      pattern of tissue distribution and the pharmacokinetic behaviour were consistent
      with a better tolerability of the novel analogue which allowed a higher
      cumulative dose to be delivered. The superior therapeutic efficacy of the
      analogue over DXR, in spite of a reduced tumour accumulation, supports an
      increased tumour selectivity.

PMID- 11239770
TI  - The three faces of paramyxovirus attachment proteins.
AB  - Enveloped viruses encode membrane-associated glycoproteins that direct the
      initial stages of virus infection. These usually oligomeric structures bind
      virions to cell surface receptors and, subsequently, direct fusion of viral
      membranes with cellular membranes. These structures are also the primary targets
      of neutralizing antibody as well as potential targets for antiviral agents. In
      several systems, solving the structure of a virus surface glycoprotein has been
      enormously valuable to our understanding of virus entry and the mechanisms of
      entry inhibition. The recent report of the structure of a paramyxovirus
      attachment protein should clarify the mechanism of cell entry by these viruses.

PMID- 11239768
TI  - An embarrassment of sortases - a richness of substrates?
AB  - A range of surface proteins is anchored to the cell walls of Gram-positive
      pathogens such as Staphylococcus aureus by the transpeptidase sortase. Until now,
      sortase-like proteins and their substrates appeared to be limited mainly to such
      pathogens. However, by searching for sortase homologues among complete and
      incomplete genome sequences, we have found them to be present in almost all Gram
      positives, a single Gram-negative bacterium and an archaean. There is usually
      more than one sortase-like protein encoded in each Gram-positive genome, and the
      genes encoding the sortase-like proteins are often clustered with genes encoding
      their likely substrates.

PMID- 11239771
TI  - Met, the HGF-SF receptor: another receptor for Listeria monocytogenes.
AB  - The bacterium Listeria monocytogenes invades a variety of cells in vitro and in
      vivo. Two proteins are crucial in this process: internalin, which interacts with
      E-cadherin, and InlB. The first identified ligand for InlB was gC1qR, which has
      no cytoplasmic domain. The newly discovered InlB receptor, Met, fits with the
      known InlB-induced signals.

PMID- 11239772
TI  - Necrotizing bacteria and protein targeting.

PMID- 11239773
TI  - Caspian seal die-off is caused by canine distemper virus.

PMID- 11239774
TI  - Sensitization to sand fly bite prevents cutaneous leishmaniasis.

PMID- 11239777
TI  - Microbial genomics.

PMID- 11239775
TI  - For whom the bug tolls.

PMID- 11239779
TI  - Sex and retrotransposons.

PMID- 11239780
TI  - New protein blocks HIV.

PMID- 11239788
TI  - Tuberculosis vaccine development: recent progress.
AB  - Recent years have seen a renewed effort to develop new vaccines against
      tuberculosis. As a result, several promising avenues of research have developed,
      including the production of recombinant vaccines, auxotrophic vaccines, DNA
      vaccines and subunit vaccines. In this article we briefly review this work, as
      well as consider the pros and cons of the animal models needed to test these new
      vaccines. Screening to date has been carried out in mouse and guinea pig models,
      which have been used to obtain basic information such as the effect of the
      vaccine on bacterial load, and whether the vaccine can prevent or reduce lung
      pathology. The results to date lead us to be optimistic that new candidate
      vaccines could soon be considered for evaluation in clinical trials.

PMID- 11239789
TI  - Is there a role for CEA in innate immunity in the colon?
AB  - Carcinoembryonic antigen (CEA) is a well known tumor marker associated with the
      progression of colorectal tumors. The CEA family of glycoproteins has been fully
      characterized and the function of some of its members is now beginning to be
      understood. Here, we advance the hypothesis that, rather than functioning in cell
      adhesion as has been suggested previously, CEA plays a role in protecting the
      colonic mucosa from microbial invasion. This hypothesis is based on new
      microscopic, molecular, phylogenetic and microbiological evidence.

PMID- 11239790
TI  - Lipid chemotaxis and signal transduction in Myxococcus xanthus.
AB  - The lipid phosphatidylethanolamine (PE) is the first chemoattractant to be
      described for a surface-motile bacterium. In Myxococcus xanthus, the specific
      activity of PE is determined by its fatty acid components. Two active species
      have been identified: dilauroyl PE and dioleoyl PE. Excitation to dilauroyl PE
      requires fibril appendages and the presence of two cytoplasmic chemotaxis
      systems, of which one (Dif) appears to mediate excitation and the other (Frz)
      appears to mediate adaptation. A possible mechanism for fibril-mediated signal
      transduction is discussed, along with the potential roles for PE chemotaxis in
      the context of the M. xanthus life cycle.

PMID- 11239791
TI  - The signal recognition particle of Archaea.
AB  - It is becoming increasingly clear that similarities exist in the manner in which
      extracytoplasmic proteins are targeted to complexes responsible for translocating
      these proteins across membranes in each of the three domains of life. In Eukarya
      and Bacteria, the signal recognition particle (SRP) directs nascent polypeptides
      to membrane-embedded translocation sites. In Archaea, the SRP protein targeting
      pathway apparently represents an intermediate between the bacterial and eukaryal
      systems. Understanding the archaeal SRP pathway could therefore reveal universal
      aspects of targeting not detected in current comparisons of the eukaryal and
      bacterial systems while possibly identifying aspects of the process either not
      previously reported or unique to Archaea.

PMID- 11239792
TI  - Tissue factor, the blood, and the arterial wall.
AB  - Thrombogenic tissue factor (TF) on cell-derived microparticles is present in the
      circulating blood of patients with acute coronary syndromes. Recently, we
      reported that leukocytes transfer TF-positive particles to platelet thrombi,
      making them capable of triggering and propagating thrombus growth. This
      observation changes the original dogma that vessel-wall injury and exposure of
      tissue factor within the vasculature to blood is sufficient for the occurrence of
      arterial thrombosis. The transfer of TF-positive leukocyte particles is dependent
      on the interaction of CD15 and TF with platelet thrombi. The inhibition of TF
      transfer and TF activity suggests a novel therapeutic approach to the prevention
      of thrombosis that may prove to be effective in disorders associated with
      increased blood TF.

PMID- 11239793
TI  - Direct vascular effects of HMG-CoA reductase inhibitors.
AB  - The 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors, or statins, are
      potent inhibitors of cholesterol synthesis and large clinical trials have
      demonstrated that these agents reduce cholesterol and the incidence of
      cardiovascular diseases. Recent evidence, however, suggests that the beneficial
      effects of statins may extend beyond their effects on serum cholesterol levels.
      Because statins also inhibit the synthesis of isoprenoid intermediates in the
      cholesterol biosynthetic pathway, they may have pleiotropic effects on vascular
      wall cells. In particular, the small GTP-binding protein, Rho, whose membrane
      localization and activity are affected by post-translational isoprenylation, may
      play an important role in mediating the direct vascular effects of statins.

PMID- 11239794
TI  - Role of rap in the biogenesis of lipoprotein receptors.
AB  - The LDL receptor gene family is composed of several endocytic receptors that
      share structural homology and function in cellular uptake of various ligands
      including lipoprotein particles. The complex structure of these lipoprotein
      receptors is highlighted by the presence of clusters of cysteine-rich ligand
      binding repeats. An important feature that is shared by all these receptors is
      the inhibition of ligand interaction by a 39-kDa receptor-associated protein
      (RAP). Recent studies have shown that under physiological conditions RAP serves
      as a molecular chaperone to assist the folding of lipoprotein receptors and their
      safe passage through the secretory pathway. Several non-exclusive models have
      been proposed regarding the molecular mechanisms of RAP function as an antagonist
      for ligand interaction with the receptors and as a molecular chaperone within the
      early secretory pathway. Elucidation of these mechanisms may provide insights
      into how biogenesis of lipoprotein receptors can be regulated via the expression
      of RAP under physiological and pathological conditions.

PMID- 11239795
TI  - Mapping of the cryptic integrin-binding site in osteopontin suggests a new
      mechanism by which thrombin can regulate inflammation and tissue repair.
AB  - The integrin alpha9beta1 mediates neutrophil migration across several ligands
      that are enriched at sites of inflammation. In one of these ligands, the acidic
      phosphoprotein osteopontin, the alpha9beta1 binding site is cryptic, but is
      revealed after thrombin cleavage. We have recently mapped the alpha9beta1 binding
      site in osteopontin to the linear peptide sequence, SVVYGLR, immediately adjacent
      to the thrombin cleavage site. Interestingly, this site is also adjacent to a
      sequence (RGD) through which five other integrins bind to osteopontin. These
      findings suggest a novel mechanism by which thrombin can modulate integrin
      signaling at sites of tissue injury.

PMID- 11239796
TI  - Signaling of G(alpha)(12) family of G proteins through a tyrosine kinase and a
      Ras-GAP.
AB  - G(12) heterotrimeric G proteins transduce signals from a number of receptors
      involved in the regulation of cardiovascular function. Recently, it has been
      discovered that these G proteins regulate the activity of Bruton's tyrosine
      kinase and Ras-GAP1(m) through a conserved PH-BM domain. These findings provide
      new insights into the signaling pathways initiated by G(12), which regulate
      cytoskeletal organization, cell proliferation and cardiovascular function.

PMID- 11239797
TI  - Cytochrome P450 2C is an EDHF synthase in coronary arteries.
AB  - Studies designed to elucidate the identity of the potent vasodilator autacoid
      endothelium-derived hyperpolarizing factor (EDHF) in the coronary vascular bed
      have highlighted a role for vascular cytochrome P450 (CYP) enzymes in
      cardiovascular homeostasis. Not only is there strong evidence suggesting that the
      putative coronary EDHF synthase is an endothelially expressed CYP epoxygenase,
      but CYP products such as epoxyeicosatrienoic acids and reactive oxygen species
      have been implicated in the regulation of intracellular signalling cascades and
      vascular cell proliferation.

PMID- 11239798
TI  - Sequence determinants of function and evolution in serine proteases.
AB  - Serine proteases of the chymotrypsin family have maintained a common fold over an
      evolutionary span of more than one billion years. Notwithstanding modest changes
      in sequence, this class of enzymes has developed a wide variety of substrate
      specificities and important biological functions such as fibrinolysis, blood
      coagulation, and complement activation. Recently it has become apparent that the
      protease domain, especially its C-terminal sequence, accounts fully for this
      functional diversity and is the most important element in shaping serine protease
      evolution.

PMID- 11239799
TI  - Contractile dysfunction in hypertrophic cardiomyopathy: elucidating primary
      defects of mutant contractile proteins by gene transfer.
AB  - Hypertrophic cardiomyopathy (HCM) is an inherited disorder of cardiac muscle that
      has been linked to mutations in the contractile proteins that make up the cardiac
      muscle sarcomere. Recent advances in cardiovascular molecular biology, including
      gene targeting and transgenesis in mice, and gene transfer technology to adult
      cardiac myocytes in primary culture, have provided new insights into how these
      mutations alter the structure-function of the cardiac muscle pump and the
      molecular mechanisms of HCM pathogenesis. In this review, we highlight the
      contributions of the application of gene transfer technology to adult cardiac
      myocytes in vitro that aim at sorting the primary effects of HCM mutant
      contractile proteins on the structure and function of cardiac muscle cells from
      the compensatory and secondary phenomenon that occur during HCM pathogenesis in
      vivo. The elucidation of the primary molecular mechanisms underlying the
      development of HCM forms a foundation by which to identify the key targets for
      disease treatment or prevention.

PMID- 11239800
TI  - What boundaries tell us about binding.

PMID- 11239801
TI  - Contextual modulation and dynamic grouping in perception.

PMID- 11239802
TI  - Sex differences in throwing: monkeys having a fling.
AB  - Fast and accurate throwing was undoubtedly important to ancestral hominids, and
      was subject to sexual-selection pressures that generated a male advantage in
      throwing accuracy that persists in modern humans. The balance of evidence,
      including that from a recent comparative study of throwing in humans and capuchin
      monkeys, suggests that high-performance throwing involves unique adaptations in
      the domains of spatial targeting, precision timing, and multi-joint motor
      control.

PMID- 11239803
TI  - Getting a grip on yourself.

PMID- 11239804
TI  - Searching for actions.

PMID- 11239806
TI  - Illusions in action.

PMID- 11239805
TI  - The psychology cyberlab.

PMID- 11239807
TI  - Judging the true potential?

PMID- 11239808
TI  - Lost for words.

PMID- 11239809
TI  - The semantics of syntactic structures.
AB  - Over the past 15 years, both linguists and psycholinguists have shown a growing
      interest in the idea that syntactic structures can carry meanings that are
      independent of the meanings of specific words. This article considers how this
      idea relates to traditional notions of compositionality in generative grammar,
      and examines two modern theories that, although based on different starting
      assumptions, both readily allow syntactic structures to bear independent meaning.
      We review work from psycholinguistics suggesting that observation alone is often
      insufficient to support the efficient learning of word meanings, and that some of
      the 'slack' left by observation can be picked up by the semantics of the
      syntactic structures in which words appear. We argue that this convergence
      between linguistic theory and psycholinguistic experimentation should be no
      surprise, because language must be learnable.

PMID- 11239810
TI  - Do action systems resist visual illusions?
AB  - Arguments about the relative independence of visual modules in the primate brain
      are not new. Recently, though, these debates have resurfaced in the form of
      arguments about the extent to which visuomotor reaching and grasping systems are
      insensitive to visual illusions that dramatically bias visual perception. The
      first wave of studies of illusory effects on perception and action have supported
      the idea of independence of motor systems, but recent findings have been more
      critical. In this article, I review several of these studies, most of which (but
      not all) can be reconciled with the two-visual-systems model.

PMID- 11239811
TI  - Neural-network models of learning and memory: leading questions and an emerging
      framework.
AB  - Real-time neural-network models provide a conceptual framework for formulating
      questions about the nature of cognition, an architectural framework for mapping
      cognitive functions to brain regions, a semantic framework for defining terms,
      and a computational framework for testing hypotheses. This article considers key
      questions about how a physical system might simultaneously support one-trial
      learning and lifetime memories, in the context of neural models that test
      possible solutions to the problems posed. Model properties point to partial
      answers, and model limitations lead to new questions. Placing individual system
      components in the context of a unified real-time network allows analysis to move
      from the level of neural processes, including learning laws and rules of synaptic
      transmission, to cognitive processes, including attention and consciousness.

PMID- 11239812
TI  - Overlapping mechanisms of attention and spatial working memory.
AB  - Spatial selective attention and spatial working memory have largely been studied
      in isolation. Studies of spatial attention have provided clear evidence that
      observers can bias visual processing towards specific locations, enabling faster
      and better processing of information at those locations than at unattended
      locations. We present evidence supporting the view that this process of visual
      selection is a key component of rehearsal in spatial working memory. Thus,
      although working memory has sometimes been depicted as a storage system that
      emerges 'downstream' of early sensory processing, current evidence suggests that
      spatial rehearsal recruits top-down processes that modulate the earliest stages
      of visual analysis.

PMID- 11239813
TI  - Human intelligence differences: a recent history.

PMID- 11239814
TI  - Erratum.

PMID- 11239815
TI  - Naegleria fowleri amoebae express a membrane-associated calcium-independent
      phospholipase A(2).
AB  - Naegleria fowleri, a free-living amoeba, is the causative agent of primary
      amoebic meningoencephalitis. Previous reports have demonstrated that N. fowleri
      expresses one or more forms of phospholipase A(2) (PLA(2)) and that a secreted
      form of this enzyme is involved in pathogenesis. However, the molecular nature of
      these phospholipases remains largely unknown. This study was initiated to
      determine whether N. fowleri expresses analogs of the well-characterized PLA(2)s
      that are expressed by mammalian macrophages. Amoeba cell homogenates contain a
      PLA(2) activity that hydrolyzes the substrate that is preferred by the 85 kDa
      calcium-dependent cytosolic PLA(2), cPLA(2). However, unlike the cPLA(2) enzyme
      in macrophages, this activity is largely calcium-independent, is constitutively
      associated with membranes and shows only a modest preference for phospholipids
      that contain arachidonate. The amoeba PLA(2) activity is sensitive to inhibitors
      that block the activities of cPLA(2)-alpha and the 80 kDa calcium-independent
      PLA(2), iPLA(2), that are expressed by mammalian cells. One of these compounds,
      methylarachidonyl fluorophosphonate, partially inhibits the constitutive release
      of [(3)H]arachidonic acid from pre-labeled amoebae. Together, these data suggest
      that N. fowleri expresses a constitutively active calcium-independent PLA(2) that
      may play a role in the basal phospholipid metabolism of these cells.

PMID- 11239816
TI  - Liposomes as sustained release system for human interferon-gamma:
      biopharmaceutical aspects.
AB  - Interferon-gamma (IFNgamma) has proven to be a promising adjuvant in vaccines
      against cancer and infectious diseases. However, due to its rapid biodegradation
      and clearance, its efficacy is severely reduced. Liposomal association might
      prolong the residence time of IFNgamma, but no efforts have been made to optimize
      the biopharmaceutical characteristics of liposomal IFNgamma for its application
      in therapy or as vaccine immunoadjuvant. In the present study, various liposomal
      formulations of recombinant human IFNgamma (hIFNgamma), differing in lipid
      composition, were prepared via the film hydration method and characterized in
      vitro regarding association efficiency and bioactivity, and in vivo regarding
      cytokine release kinetics after subcutaneous (s.c.) administration into mice.
      Human IFNgamma can be formulated in large, multilamellar liposomes with high
      association efficiency (>80%) and preservation of bioactivity. A critical
      parameter is the inclusion of negatively charged phospholipids to obtain a high
      liposome association efficiency, which is dominated by electrostatic
      interactions. The fraction of externally adsorbed protein compared to the total
      associated protein can be minimized from 74+/-9% to 8+/-3% by increasing the
      ionic strength of the dispersion medium. After injection of free (125)I
      hIFNgamma, the radiolabel was detectable up to 48 h at the injection site.
      Liposomal encapsulation of (125)I-hIFNgamma increased the local area under the
      curve 4-fold, and the presence of the radiolabeled hIFNgamma at the injection
      site was prolonged to 7 days. The release kinetics and overall residence time of
      the cytokine at the s.c. administration site was influenced by depletion of the
      externally adsorbed IFNgamma, reducing the initial burst release. Increasing the
      rigidity of the liposome bilayer also resulted in a more pronounced reduction of
      the burst release and a 19-fold increase in the residence time of the protein at
      the s.c. administration site, compared to the free cytokine. As adjuvanticity of
      liposomal IFNgamma may strongly depend on the release kinetics of cytokines in
      vivo, the findings in this paper may contribute to a rational design of liposomal
      cytokine adjuvants in vaccines against cancer and infectious diseases.

PMID- 11239817
TI  - Retinoylation of proteins in cell-free fractions of rat tissues in vitro.
AB  - all-trans-Retinoic acid, a highly active form of vitamin A in inducing cellular
      differentiation, is incorporated covalently into proteins both in vivo and in
      vitro. The relative rates of incorporation of all-trans-11,12-(3)H-retinoic acid
      into rat tissue homogenates in the presence of ATP and coenzyme A were
      testes>>lung> or =brain> or =kidney>liver. Although all studied cellular
      organelles of the testes incorporated (3)H-retinoic acid into protein,
      mitochondria were by far the most active; indeed, up to 25% of the added
      tritiated retinoic acid (RA) became covalently bound to protein in a 90 min
      incubation period. In the absence of ATP, coenzyme A, or both cofactors, the
      amount of RA incorporated into the proteins of testes mitochondria fell to 37%,
      16%, and 11%, respectively, of that incorporated in their presence. N
      Ethylmaleimide (5 mM) strongly inhibited the reaction. Boiled mitochondria were
      inactive. After extensive extraction with CHCl(3)-CH(3)OH, the protein-bound
      radioactivity, which proved largely to be retinoic acid, was released by
      treatment with proteinase K, hydroxylamine, and dilute base. Thus, retinoic acid
      is most probably linked to protein as a thiol ester. By SDS-polyacrylamide gel
      electrophoresis, four protein fractions with molecular masses of approx. 20, 24,
      29, and 45 kDa, as well as smaller amounts of larger entities, were labeled in
      testes mitochondria. The possible identities and roles of these retinoylated
      proteins are currently being explored.

PMID- 11239818
TI  - Primary cultures of human hepatocytes but not HepG2 hepatoblastoma cells are
      suitable for the study of glycosidic conjugation of bile acids.
AB  - To define the role of glycosidic conjugation of bile acids in humans, an in vitro
      model system is desirable. We studied the formation of glycosidic conjugates of
      bile acids in primary cultures of human hepatocytes, isolated from organ donor
      liver, and the human hepatoblastoma cell line, HepG2. Cells were incubated with
      100 microM bile acids (chenodeoxycholic, CDCA; hyodeoxycholic, HDCA; and
      isoursodeoxycholic acids, isoUDCA) and 1-2 mM uridine diphosphoglycosides (UDP
      glucose, UDP-Glc; UDP-glucuronic acid, UDP-GlcA, and UDP-N-acetylglucosamine, UDP
      GlcNAc), and octyl glucoside. Media were analysed by electrospray-/gas
      chromatography-mass spectrometry and electrospray with collision induced
      dissociation. Primary cultures of human hepatocytes formed glycosidic bile acid
      conjugates with UDP-sugars (6alpha-Glc-HDCA, 6alpha-GlcA-HDCA, and 7beta-GlcNAc
      isoUDCA) and octyl glucoside as sugar donors (3alpha-Glc-CDCA). HDCA was
      completely metabolised to either Glc-HDCA, a compound yet not found in vivo, or
      GlcA-HDCA. No glycosidic bile acid conjugate was found in media from experiments
      with HepG2. Thus, primary cultures of human hepatocytes, but not HepG2, are
      suitable in vitro systems for the study of glycosidic bile acid conjugation
      reactions.

PMID- 11239819
TI  - The growth inhibitory effect of conjugated linoleic acid on a human hepatoma cell
      line, HepG2, is induced by a change in fatty acid metabolism, but not the
      facilitation of lipid peroxidation in the cells.
AB  - We investigated the growth inhibitory effect of conjugated linoleic acid (CLA) on
      HepG2 (human hepatoma cell line), exploring whether the inhibitory action occurs
      via lipid peroxidation in the cells. When the cells were incubated up to 72 h
      with 5-40 microM of CLA (a mixture of 9c,11t-18:2 and 10t,12c-18:2), cell
      proliferation was clearly inhibited in a dose and time dependent manner but such
      an inhibition was not confirmed with linoleic acid (LA). In order to evaluate the
      possible contribution of lipid peroxidation exerted by CLA to cell growth
      inhibition, alpha-tocopherol (5-20 microM) and BHT (1-10 microM) as potent
      antioxidants were added to the medium with CLA (20 microM), which did not restore
      cell growth at all. Furthermore, after 72 h incubation, the membranous
      phospholipid hydroperoxide formation in the CLA-supplemented cells was suppressed
      respectively to 25% and 50% of that in LA-supplemented cells and control cells.
      No difference was observed by a conventional lipid peroxide assay, the TBA test,
      between CLA-supplemented cells and LA-supplemented cells. Although the cellular
      lipid peroxidation was not stimulated, lipid contents (triacylglycerol, total
      cholesterol and free cholesterol) and fatty acid contents (palmitic acid,
      palmitoleic acid and stearic acid) markedly increased in CLA-supplemented cells
      compared with LA-supplemented and control cells. Moreover, supplementation with
      20 microM LA and 20 microM arachidonic acid profoundly interfered with the
      inhibitory effect of CLA in HepG2. These results suggest that the growth
      inhibitory effect of CLA on HepG2 is due to changes in fatty acid metabolism but
      not to lipid peroxidation.

PMID- 11239820
TI  - Cloning and direct G-protein regulation of phospholipase D from tobacco.
AB  - Phospholipase D (PLD) and heterotrimeric G-proteins are involved in plant signal
      transduction pathways at the plasma membrane. There is evidence suggesting that
      PLD acts downstream from G-proteins, but a direct interaction of specific members
      has not been shown. In the present paper, a PLD cDNA clone was isolated from
      tobacco, expressed as a GST fusion in bacteria, and the recombinant protein was
      purified by glutathione affinity. Its enzymatic properties identified it as an
      alpha-type PLD. The alpha-subunit of a G-protein from tobacco was isolated in a
      similar way. Both proteins were functional in biochemical assays. When the G
      protein was included in the PLD assay, a strong dosage-dependent inhibition of
      the PLD activity was observed. Different control proteins did not exhibit this
      inhibitory effect. When GST-NtGPalpha1 was activated by incubation with GTPgammaS
      the inhibitory activity was greatly reduced. These results provide a first
      indication for a direct regulation of PLDalpha by a heterotrimeric G-protein
      alpha-subunit in plants.

PMID- 11239821
TI  - Impairment of bile salt-dependent lipase secretion in AR4-2J rat pancreatic cells
      induces its degradation by the proteasome.
AB  - Bile salt-dependent lipase (BSDL, EC 3.1.1.13) is a lipolytic enzyme normally
      secreted by the pancreatic acinar cell. Co- and post-translational modifications,
      such as N- and O-linked glycosylation, regulate the secretion of this enzyme;
      therefore it was of first importance to determine the behaviour of BSDL under
      conditions that impaired its secretion. Using AR4-2J pancreatic cells as model,
      we showed, particularly when BSDL secretion is impaired, that proteasome
      inhibitors increased the amount of intracellular BSDL, suggesting that the
      proteasome is involved in the degradation of this protein. This was strengthened
      by the detection of ubiquitinated BSDL and of degradation product. Our results
      suggested that both ubiquitination and degradation of the enzyme occurred at the
      level of the cytosolic side of microsome membranes. ATP hydrolysis appears
      essential in ubiquitinated BSDL association with membranes and degradation.
      Furthermore, under normal secretory conditions, we have shown that a fraction of
      ubiquitinated BSDL is neither O-glycosylated nor N-glycosylated, suggesting that
      the N-glycosylation-deficient proteasome substrate does not reach the Golgi and
      could be degraded by the ER-associated degradation machinery. However, another
      fraction of ubiquitinated BSDL that is deficient in O-glycosylation, carries out
      endoglycosidase H-insensitive N-linked glycans, meaning that a second system,
      that detects abnormal BSDL molecules, could also operate at the level of the
      Golgi compartment. Consequently, it appears that impairment of BSDL secretion
      consecutive to secretion inhibition or to a deficient glycosylation leads to the
      proteasome-ubiquitin-dependent degradation of the protein. Therefore, this
      pathway is part of the quality control involved in BSDL secretion.

PMID- 11239822
TI  - Effects of bile salts on cholestan-3beta,5alpha,6beta-triol-induced apoptosis in
      dog gallbladder epithelial cells.
AB  - Oxysterols are cytotoxic agents. The gallbladder epithelium is exposed to high
      concentrations of oxysterols, and so elucidating the mechanisms of cytotoxicity
      in this organ may enhance our understanding of the pathogenesis of biliary tract
      disorders. We investigated the cytotoxic effects of the oxysterol cholestan
      3beta,5alpha,6beta-triol (TriolC) on dog gallbladder epithelial cells. Apoptosis
      was the major form of cytotoxicity, as determined by analysis of nuclear
      morphologic changes and by multiparameter flow cytometry. Hydrophobic bile salts
      are known to have cytotoxic effects, whereas hydrophilic bile salts have
      cytoprotective effects. We therefore examined whether the hydrophobic bile acid
      taurodeoxycholic acid (TDC) and the hydrophilic bile acid tauroursodeoxycholic
      acid (TUDC) had modifying effects on oxysterol-induced cytotoxicity. TriolC
      caused an increase in the number of apoptotic cells from 14+/-11% (control) to
      48+/-12% of total cells (P<0.01). After combining TriolC with TDC, cell apoptosis
      increased to 63+/-16% (P<0.05), whereas after addition of TUDC, the number of
      apoptotic cells decreased to 31+/-12% (P<0.05) of total cells. In summary,
      oxysterols such as TriolC induce apoptosis. Hydrophobic bile salts enhance TriolC
      induced apoptosis, whereas hydrophilic bile salts diminish TriolC-induced
      apoptosis. These results suggest that interactions between oxysterols and bile
      salts play a role in the pathophysiology of biliary tract disorders.

PMID- 11239823
TI  - 7-Ketocholesterol delivered to mice in chylomicron remnant-like particles is
      rapidly metabolised, excreted and does not accumulate in aorta.
AB  - Cholesterol oxidation products (oxysterols) have been implicated in atherogenesis
      due to their presence in atherosclerotic tissue and their potent effects in
      vitro. One of the major oxysterols currently of interest is 7-ketocholesterol
      (7K) and it has been suggested that the diet is an important source of this
      oxysterol. This investigation tested the hypothesis that 7K, delivered in a
      physiologically relevant vehicle, chylomicron remnant-like emulsion (CMR), would
      be metabolised and excreted by mice in a similar manner and to a similar extent
      as previously observed in rats when delivered in a chemically modified
      lipoprotein, acetylated low-density lipoprotein (acLDL). Indeed, the metabolism
      of 14C-7K delivered in CMR mirrored that of acLDL and was much more rapid than
      (3)H-cholesterol delivered simultaneously. The 7K-derived (14)C was cleared from
      the liver, appeared in the intestine and was excreted in the faeces. A
      substantial proportion of the 7K-derived (14)C in the intestine and faeces was
      aqueous-soluble, indicating metabolism to polar products, presumably bile acids.
      Moreover, while cholesterol-derived (3)H increased in the aorta, (14)C appeared
      transiently and there was no observable accumulation within 24 h. The data
      confirm our previous findings of rapid hepatic metabolism of 7K when delivered in
      acLDL and demonstrate that 7K delivered in a vehicle of dietary significance is
      similarly metabolised and excreted. Indeed, the data encourage further
      investigation into the contribution that dietary oxysterols may or may not make
      to atherogenesis.

PMID- 11239824
TI  - Comparison of the metabolism of L-erythro- and L-threo-sphinganines and ceramides
      in cultured cells and in subcellular fractions.
AB  - Ceramide (Cer) is a key intermediate in the synthetic and degradative pathways of
      sphingolipid metabolism, and is also an important second messenger. Natural Cer
      exists in the D-erythro configuration. Three additional, non-natural
      stereoisomers exist, but conflicting reports have appeared concerning their
      metabolism. We now compare the stereospecificity of three enzymes in the
      sphingolipid biosynthetic pathway, namely dihydroceramide (dihydroCer),
      sphingomyelin (SM) and glucosylceramide synthases, in subcellular fractions and
      in cultured cells. The L-erythro enantiomers of sphinganine, dihydroCer and Cer
      do not act as substrates for any of the three enzymes. In contrast, the
      diastereoisomer, L-threo-sphinganine, is acylated by dihydroCer synthase, and L
      threo-dihydroCer and L-threo-Cer are both metabolized to dihydroSM and SM,
      respectively, but not to dihydroglucosylceramide and glucosylceramide. No
      significant difference was detected in the ability of SM synthase to metabolize
      Cer containing a short (hexanoyl) versus long acyl chain (palmitoyl),
      demonstrating that short-acyl chain Cers mimic their natural counterparts, at
      least in the sphingolipid biosynthetic pathway.

PMID- 11239825
TI  - Desferrioxamine, an iron chelator, upregulates cyclooxygenase-2 expression and
      prostaglandin production in a human macrophage cell line.
AB  - Prostaglandins (PGs) play regulatory roles in a variety of physiological and
      pathological processes, including the immune response, cytoprotection and
      inflammation. Desferrioxamine (DFX), an iron chelator, is known to reduce free
      radical-mediated cell injury and to upregulate certain inflammatory mediators. We
      investigated the effects of DFX on the production of PGs and the expression of
      cyclooxygenase-2 (COX-2), the rate-limiting enzyme in the synthesis of PGs, using
      a human macrophage cell line, U937. Our results showed that COX-2 expression and
      PGE(2) production are upregulated by DFX treatment and that this upregulation is
      dependent on both COX-2 promoter activity and alteration of mRNA stability. COX-2
      promoter activity may be, at least in part, mediated by activation of the
      extracellular signal-regulated kinase pathway. These findings suggest that iron
      metabolism may regulate inflammatory processes by modulating PGs as well as other
      inflammatory mediators.

PMID- 11239826
TI  - In vivo substrates and the contribution of the common phospholipase D, PLDalpha,
      to wound-induced metabolism of lipids in Arabidopsis.
AB  - The common plant phospholipase D (PLD), PLDalpha, has been proposed to be
      involved in wound-induced production of jasmonic acid. To better understand the
      role(s) of PLDalpha in the wound response, detailed lipid analysis was carried
      out to determine the in vivo substrates and the contribution of PLDalpha in wound
      induced lipid metabolism in Arabidopsis thaliana. Mechanical wounding of
      Arabidopsis leaves resulted in significantly less hydrolysis of
      phosphatidylcholine (PC) in PLDalpha-deficient than in wild-type plants.
      Hydrolysis of phosphatidylethanolamine, phosphatidylglycerol (PG), and
      phosphatidylinositol within 30 min of wounding was not significantly different in
      PLDalpha-deficient and wild-type leaves. Phosphatidic acid (PA) levels increased
      rapidly in wild-type and, to a lesser extent, in PLDalpha-deficient plants. The
      acyl composition of the PA generated by wounding suggests that the major in vivo
      substrate of PLD in wild-type leaves was PC, and that PG hydrolysis accounted for
      10-15% of the wound-induced PA in wild-type leaves. Comparison of the acyl
      compositions of the wound-induced PA of wild-type and PLDalpha-deficient leaves
      indicated that PLDalpha hydrolyzed PG more readily than other PLD isoforms did.
      Wounding produced substantial increases in free linoleic and linolenic acids in
      wild-type plants, whereas PLDalpha-deficient plants showed only a slight increase
      in linoleic acid and no significant increase in linolenic acid. These results
      demonstrate that PLDalpha and at least one other PLD isoform, as well as other
      hydrolytic enzymes, are active in mechanically wounded Arabidopsis leaves, and
      PLDalpha is involved in wound-induced metabolism of polyunsaturated fatty acids.

PMID- 11239827
TI  - The genetic regulation of liver microsomal CYP2E1 activity among strains of the
      viviparous fish Poeciliopsis.
AB  - CYP2E1 expression was examined within, among, and in F(1) and backcross progeny
      of strains (P. monacha S68-5; P. viriosa M65-23) of the viviparous fish
      Poeciliopsis. CYP 2E1 activity varied dramatically in P. monacha, and P. viriosa
      (3.9+/-0.8 and 9.6+/-1.3 microg/min/mg) as well as the temperature which gave
      maximal activity (T(0)=25 degrees C and 31 degrees C). F(1) individuals from a
      crosses between P. monacha and P. viriosa, produced progeny whose CYP2E1 activity
      segregated into three different groups: (1) phenotypically the same as P.
      viriosa; (2) intermediate between the two parental strains; and (3)
      phenotypically the same as P. monacha. When a male P. monacha was crossed with a
      female P. viriosa 25% of the offspring had an intermediate phenotype and 65% the
      maternal P. viriosa phenotype. From the same cross, 85% of the females progeny
      had the maternal phenotype, while 80% of male progeny had the intermediate and
      paternal phenotype, suggesting an effect of the maternal genome on the F(1)
      phenotype. Among F(1) fish the T(0) was evenly distributed between parental
      values. In the backcross of a F(1) female to a male P. viriosa, CZX-6-hydroxylase
      activity segregated into the same three phenotypes with 60% of the progeny
      expressing the P. monacha phenotype. From the same cross, 70% of females and 40%
      of males expressed the P. monacha phenotype. The T(0) in the backcross were
      evenly distributed between the two parental values and the sex ratio among
      progeny was different than expected.

PMID- 11239828
TI  - Tea catechins inhibit cholesterol oxidation accompanying oxidation of low density
      lipoprotein in vitro.
AB  - Endogenous oxidized cholesterols are potent atherogenic agents. Therefore, the
      antioxidative effects of green tea catechins (GTC) against cholesterol oxidation
      were examined in an in vitro lipoprotein oxidation system. The antioxidative
      potency of GTC against copper catalyzed LDL oxidation was in the decreasing order
      (-)-epigalocatechin gallate (EGCG)=(-)-epicatechin gallate (ECG)>(-)-epicatechin
      (EC)=(+)-catechin (C)>(-)-epigallocatechin (EGC). Reflecting these activities,
      both EGCG (74%) and ECG (70%) inhibited the formation of oxidized cholesterol, as
      well as the decrease of linoleic and arachidonic acids, in copper catalyzed LDL
      oxidation. The formation of oxidized cholesterol in 2,2'-azobis(2-amidinopropane)
      hydrochloride (AAPH)-mediated oxidation of rat plasma was also inhibited when the
      rats were given diets containing 0.5% ECG or EGCG. In addition, EGCG and ECG
      highly inhibited oxygen consumption and formation of conjugated dienes in AAPH
      mediated linoleic acid peroxidative reaction. These two species of catechin also
      markedly lowered the generation of hydroxyl radical and superoxide anion. Thus,
      GTC, especially ECG and EGCG, seem to inhibit cholesterol oxidation in LDL by
      combination of interference with PUFA oxidation, the reduction and scavenging of
      copper ion, hydroxyl radical generated from peroxidation of PUFA and superoxide
      anion.

PMID- 11239829
TI  - The influence of zinc on apical uptake of cadmium in the gills and cadmium influx
      to the circulatory system in zebrafish (Danio rerio).
AB  - Zn (0-16 microM) effects on apical Cd uptake from the water into the branchial
      epithelium and influx of Cd from the water to the circulatory system in zebrafish
      (Danio rerio) were studied in three experiments. Apical Cd uptake was decreased
      by Zn in all three experiments. In fish exposed to 1-600 nM Cd (experiment 1),
      apical Cd uptake showed saturation kinetics at 2 and 4 microM Zn, and a
      competitive interaction was indicated. At 16 microMZn, Cd uptake increased
      linearly. Cadmium influx did not show saturation kinetics, but was inhibited by
      16 microM Zn at low Cd exposure concentrations. In fish exposed to 0.1-600 nM Cd
      (experiment 2), Cd uptake was inhibited by 16 microM Zn, whereas at 30 nM Cd
      uptake was inhibited by 2 microM Zn. Similarly, 2 microM Zn did not influence Cd
      uptake in fish exposed to 0.1-2 nM Cd (experiment 3), whereas 2 microM Zn
      inhibited uptake at 8-30 nM Cd. Zinc also inhibited Cd influx at higher Cd
      concentrations. However, at lower Cd exposures, a Zn-induced increased influx was
      indicated. Zinc influences the Cd uptake and influx processes at several sites in
      the branchial epithelial cells, indicating that influx of Zn2+ and Cd2+ occurs
      through common pathways.

PMID- 11239830
TI  - Normobaric hyperoxic stress in budgerigars: enzymic antioxidants and lipid
      peroxidation.
AB  - The effects of acute (3 h), repeated acute (3 exposures each of 3 h) and chronic
      (72 h) normobaric hyperoxic exposure in budgerigars (Melopsittacus undulatus)
      were evaluated by monitoring the effects on pulmonary enzymic antioxidants, and
      indicators of lipid peroxidation. All durations of oxygen exposure resulted in
      significant respiratory alkalosis and elevated pulmonary and blood glutathione
      peroxidase concentrations. The concentrations of other pulmonary enzymic
      antioxidants including glutathione reductase and superoxide dismutase were not
      significantly altered by oxygen exposure. Pulmonary concentrations of the lipid
      peroxidation markers malonaldehyde and 4-hydroxyalkenal were not significantly
      elevated following oxygen exposure. Plasma concentrations of 8-epi isoprostane
      F(2alpha) were significantly elevated following both acute and repeated acute
      exposure. The results indicate that in budgerigars, both acute and chronic oxygen
      exposure can result in significant alteration in respiratory function and
      increased production of reactive oxygen species.

PMID- 11239831
TI  - Normobaric hyperoxic stress in budgerigars: non-enzymic antioxidants.
AB  - The effects of oxygen exposure on pulmonary and blood non-enzymic antioxidant
      concentrations was evaluated in budgerigars (Melopsittacus undulatus).
      Budgerigars were exposed to acute (3 h), repeated acute (3 exposures each of 3 h)
      or chronic (72 h) normobaric hyperoxic environments and the pulmonary and plasma
      concentrations of selected non-enzymic antioxidants, namely glutathione, uric
      acid, alpha- and gamma-tocopherol and carotenoids were assayed. With increasing
      duration of oxygen exposure, the ratio of oxidised to reduced glutathione was
      significantly increased, while the concentrations of uric acid, alpha- and gamma
      tocopherol and carotenoids were significantly reduced, especially following
      chronic oxygen exposure. Following acute and repeated acute exposure, alteration
      in glutathione concentrations and reduction in alpha-tocopherol concentrations
      indicated oxygen stress. Following chronic exposure, depletion of non-enzymic
      antioxidants indicated exhaustion of these protective mechanisms and progression
      from oxygen stress to oxygen toxicity.

PMID- 11239832
TI  - Metal accumulation and metallothionein in brown trout, Salmo trutta, from two
      Norwegian rivers differently contaminated with Cd, Cu and Zn.
AB  - In this work we have studied the accumulation of heavy metals in two brown trout
      (Salmo trutta) populations in their natural environment and the participation of
      metal binding to metallothionein (MT) in this process. Cd, Cu and Zn
      concentrations, total MT (including Cu MT) and Cd/Zn MT were measured in the
      gills, liver and kidney of trout inhabiting two rivers, one Cu-contaminated and
      the other Cd/Zn-contaminated, located at Roros, Central Norway. In both
      populations, high levels of Cu were found in the liver, whereas Cd was
      accumulated in liver and particularly in the kidney. The proportions of Cd/Zn MT
      and Cu MT in liver and kidney, but not in gills, reflected the accumulated and
      the environmental concentrations of these metals. The total Cu MT concentrations
      in the investigated tissues, however, were highest in trout from the river with
      the lowest ambient Cu concentration. It is suggested that MTs are of less
      importance in Cu-acclimated trout. The data also suggest that acclimation to a Cu
      rich environment involves reduced Cu accumulation or increased Cu elimination. In
      trout from the Cd-rich environment, this metal was mainly bound to MT, whereas in
      trout from the Cu-rich environment Cd was also associated with non-MT proteins.
      These findings emphasize the importance to determine both Cd/Zn MT and Cu MT
      levels, when the participation of this protein in metal handling in trout tissues
      is investigated.

PMID- 11239833
TI  - Exogenous melatonin affects lipids and enzyme activities in mink (Mustela vison)
      liver.
AB  - Exogenous melatonin as subcutaneous 2.7-mg implants was given to eight female and
      male minks in late July with an equal number of animals in the control groups.
      The liver enzyme activities and major lipids of liver and plasma were measured in
      October-November. Melatonin had very pronounced effects on the lipid and
      carbohydrate metabolism of the minks and there was also a clear sexual
      dimorphism. In the males, melatonin decreased the lipase esterase activity of the
      liver. In the liver of the females, however, melatonin increased the glucose-6
      phosphatase activity. Due to melatonin treatment the liver triacylglycerol
      contents diminished in both sexes. At the same time, in the females the liver
      cholesterol levels were decreased. In the plasma lipids, the only change was a
      fall in the polar lipids of the melatonin-treated females. Melatonin seems to be
      responsible for the metabolic changes associated with the onset of wintering,
      especially for the acceleration of the deposition of subcutaneous fat reserves.
      The smaller females experience the effects of exogenous melatonin more rapidly
      than the males. Perhaps the smaller body size requires an earlier onset of
      metabolic preparation for the winter.

PMID- 11239834
TI  - Evaluation of estrogenic effects of municipal effluents to the freshwater mussel
      Elliptio complanata.
AB  - Municipal effluents are an important source of estrogens to the aquatic
      environment. The purpose of this study was to examine the estrogenicity of
      municipal effluents to the indigenous freshwater mussel, Elliptio complanata.
      First, estradiol-binding sites in gonad homogenates were characterized to
      determine the binding affinity and specificity of estrogens. Mussels were exposed
      to increasing concentrations of a municipal effluent for 96 h at 15 degrees C. In
      another experiment, mussels were placed in cages and submerged for 62 days at 1.5
      km upstream and 5 km downstream of a municipal effluent plume in the St. Lawrence
      River. Mussels were harvested for assessment of vitellogenin-like proteins in the
      hemolymph and determination of total lipid, carbohydrate and protein in the
      gonad. The presence of specific estrogen-binding sites was found in both male and
      female gonads. Binding of estradiol to cytosol proteins reached saturation,
      yielding a dissociation constant of 0.4 nM. Vitellogenin (Vg) levels increased
      significantly in both the hemolymph and the gonad after exposure to the effluent.
      Moreover, females appeared to be more sensitive than males to producing Vg.
      Mussels exposed in situ to contaminated surface waters had higher levels of Vg at
      the downstream site, again, females had higher levels of Vg than did males. On
      the other hand, lipid and sugar levels in male gonads were significantly
      increased at the downstream site. Moreover, mussels at the downstream site had
      decreased shell growth length and increased total and soft tissue weights. We
      conclude that municipal effluents contain bio-available xenoestrogens at levels
      sufficient to elicit effects in freshwater mussels.

PMID- 11239836
TI  - Mosquitofish (Gambusia affinis) vitellogenin: identification, purification, and
      immunoassay.
AB  - Vitellogenin is a phospholipoglycoprotein precursor of egg yolk. In mature female
      fish, vitellogenin is synthesized and secreted by the liver in response to
      circulating estrogens. Vitellogenin is normally undetectable in the blood of male
      fish, but can be induced by exposure to compounds possessing estrogenic activity.
      Thus, the presence of vitellogenin in blood of male fish can serve as a useful
      biomarker for assessing previous exposure to estrogenic compounds. In the present
      study, we report identification and purification of vitellogenin in the
      mosquitofish (Gambusia affinis). Anti-vitellogenin immune serum was generated and
      used to develop an immunoblot assay for detection of vitellogenin. A combination
      of immunoblotting and densitometric scanning was used to assess the time- and
      dose-dependent effects of 17alpha-ethynylestradiol on vitellogenesis in male G.
      affinis. The results indicate that changes in the level of vitellogenin in
      mosquitofish blood can be reliably detected by the immunoblot assay, and that the
      mosquitofish may be a useful bioindicator organism for detecting estrogenic
      contamination of the aquatic environment.

PMID- 11239835
TI  - Glutathione S-transferases from rainbow trout liver and freshly isolated
      hepatocytes: purification and characterization.
AB  - Glutathione S-transferases (GST) form an important family of biotransformation
      enzymes catalyzing the conjugation of glutathione to a great variety of
      xenobiotic compounds. The objective of this study was to compare the different
      characteristics of GST from freshly isolated rainbow trout hepatocytes with those
      corresponding to the total liver of the same fish, in order to establish the
      similarities. GST was purified by affinity chromatography and enzymatic activity
      was determined towards two substrates, 1-chloro-2,4-dinitrobenzene (CDNB) and
      ethacrynic acid (ETHA). The different isoenzymes were determined by HPLC
      associated with SDS-PAGE. Slight differences between the samples were obtained
      when the results corresponding to the enzyme activity were compared. HPLC results
      showed that all GST isoforms present in the total liver samples were represented
      in the isolated cells too, corresponding to isoforms with molecular masses of
      approximately 25.5 and 23.0 kDa.

PMID- 11239837
TI  - Interaction of cysteine proteases with calciotropic hormone receptors.
AB  - The effect of two cysteine proteases: papain and a cathepsin L-like enzyme
      purified from the oesophagus of Nephrops norvegicus (NCP) was studied on the
      specific binding of calcitonin (CT) and calcitonin gene related peptide (CGRP) to
      rat kidney and liver membranes, respectively. In addition, the response of
      adenylyl cyclase to increasing concentrations of these two enzymes was
      investigated. Each protease inhibited the initial CGRP and CT binding to rat
      liver and kidney membranes, respectively, in a manner not significantly different
      from that obtained in the presence of the unlabeled standard. The adenylyl
      cyclase activity in rat liver membranes was increased by the addition of each
      enzyme. The response was higher with papain that induced a fivefold increase of
      enzyme activity at a 4-microg/ml enzyme concentration. In rat kidney membranes,
      the magnitude of the response was identical with both enzymes. In contrast with
      NCP, papain induced a biphasic response. Leupeptin and E(64), two specific
      inhibitors of cysteine proteases, reversed the observed effects. Trypsin induced
      an inhibition of the liver membrane adenylyl cyclase activity and an activation
      in rat kidney membranes at low protease concentration. Thus, cysteine proteases
      are able to act, in vitro, at the receptor level in target organs specific for
      calciotropic hormones.

PMID- 11239838
TI  - The acute phase response in Japanese quail (Coturnix coturnix japonica).
AB  - Experiments were conducted to determine the effect of injection of
      lipopolysaccharide (LPS, from S. typhimurium) or muramyl dipeptide (MDP, N
      acetylmuramyl-L-ala-isoglutamine) in Japanese quail. Doses of MDP between 0.3 and
      10 mg/kg body wt. had no effect on body temperature. In contrast, doses of 1.0
      22.5 mg LPS/kg body wt. caused significant increases in body temperature. None of
      the doses of LPS or MDP resulted in mortality. The febrile response to LPS was
      diminished following a second injection 48 h after the first, and was absent
      following a third injection. Plasma zinc, an indicator of the acute phase
      response, was significantly reduced by either LPS or MDP after the first
      injection (P<0.001), but not after the second or third injection. Splenic
      interleukin 1-beta (IL-1beta) mRNA expression was increased after the first and
      last injection of LPS (P<0.001), but only after the first injection of MDP
      (P<0.005). Hepatic IL-1beta mRNA expression was increased after the first, but
      not the third injection of LPS (P<0.001), while MDP had no effect. These data
      indicate that Japanese quail are less sensitive to MDP than LPS, and that quail
      demonstrate tolerance to LPS following repeated injections.

PMID- 11239839
TI  - Do ATP and UTP involve cGMP in positive inotropism on rat atria?
AB  - ATP and UTP induced a dual inotropic effect in rat left atria: first a decrease
      and then an increase in contractile tension were observed. PPADS, an antagonist
      of P2X receptors, inhibited positive inotropism induced by ATP and alpha,beta
      meATP. Chiefly, we investigated intracellular mechanisms responsible for the
      positive inotropism. We tested cromakalim and glibenclamide, an activator and an
      inhibitor, respectively, of ATP-sensitive K(+) channels. These compounds did not
      influence the effects of ATP. IBMX, a phosphodiesterase inhibitor, and H-7, an
      inhibitor of protein kinase C and cAMP-dependent protein kinase, did not modify
      the inotropic effects of ATP. Instead, H-8, an inhibitor of cAMP- and cGMP
      dependent protein kinases, strongly inhibited the positive effects of both ATP
      and UTP, suggesting the possible involvement of cGMP in the inotropism. Also, LY
      83583, an inhibitor of cGMP production, reduced positive inotropism by alpha,beta
      meATP, ATP and UTP. Moreover, 8-Br-cGMP (50 microM), a stable analogue of cGMP,
      inhibited positive inotropism by all nucleotides. Lastly, we determined
      intracellular cGMP levels by RIA; the cyclic nucleotide increased during positive
      inotropism induced by ATP and UTP. The results regarding positive inotropism
      suggest that: (a) ATP acts through P2X receptors, while UTP may act by P2X, but
      also through PPADS-insensitive receptors; and (b) changes in intracellular cGMP
      concentration are involved in this inotropic effect.

PMID- 11239840
TI  - The nootropic drug vinpocetine modulates different types of potassium currents in
      molluscan neurons.
AB  - Three types of high-threshold K+ currents were recorded in isolated neurons of
      the snail Helix pomatia using a two-microelectrode voltage clamp technique:
      transient K+ current (I(A)), delayed rectifier (I(KD)) and Ca2+-dependent K+
      current (I(K(Ca))). Vinpocetine (1-100 microM) applied to the bath affected
      different types of K+ current in different ways: I(A) was increased (35+/-14%),
      I(KD) was moderately inhibited (20+/-9%) and I(K(Ca)) was strongly suppressed
      (45+/-15%). When I(A) and I(K(Ca)) were present in the same cell, vinpocetine
      exerted a dual effect on the total K+ current, depending on the amplitude of the
      test stimulus. In the presence of vinpocetine, the I-V curve crossed the control
      I-V curve. The inhibition of I(K(Ca)) by vinpocetine between 1 and 100 microM is
      unlikely to be a result of Ca2+ current (I(Ca)) suppression, as the latter was
      inhibited only at vinpocetine concentrations exceeding 300 microM. Dibutyryl
      cyclic GMP (dbcGMP) (but not dbcAMP) mimicked the effects of vinpocetine in the
      majority of cells tested (coefficient of correlation r=0.60, P<0.05, n=22). The
      data suggest that modulation of different types of K+ current in neuronal
      membrane can contribute, at least partially, to the nootropic effect of
      vinpocetine through the regulation of intracellular Ca2+ concentration.

PMID- 11239841
TI  - Induced CYP1A mRNA, protein and catalytic activity in the liver of feral fish,
      leaping mullet, Liza saliens.
AB  - In this study, we examined whether levels of P4501A mRNA expression were
      naturally induced in feral fish, Liza saliens, and whether CYP1A protein levels
      and associated enzyme activity, EROD, were also increased. Induction of mRNA was
      measured using a nucleic acid hybridization technique. For the hybridization
      studies, a new 33-mer oligonucleotide probe 5'-dCTC ATC CAG CTT CCT GTC CTC GCA
      GTG ATC AAT-3' was designed, which corresponded to the totally conserved amino
      acid motif of CYP1A protein from positions 291 to 301 among the various fish
      species. Results of Northern blot analysis revealed that RNA isolated from the
      liver of mullet collected from the highly contaminated region of Izmir Bay with a
      dissolved and dispersed petroleum hydrocarbon content of 12.45 microg l(-1) gave
      a strong hybridization signal, whereas only a weak hybridization signal was
      detected in the liver RNA of fish caught from the reference site containing less
      than 1 microg l(-1) of petroleum hydrocarbons. Similarly, fish from the
      contaminated site had approximately 80 times more EROD activity than the feral
      fish captured from the reference site. Studies using polyclonal antibodies
      produced against purified mullet CYP1A also showed the similar trend. In
      conclusion, feral leaping mullet caught from contaminated water displayed
      induction of CYP1A at three levels of expression, namely, mRNA, apoprotein and
      catalytic activity.

PMID- 11239842
TI  - Complete bundle branch block as an independent predictor of all-cause mortality:
      report of 7,073 patients referred for nuclear exercise testing.
AB  - PURPOSE: Complete left bundle branch block is a well-established independent risk
      factor for mortality, but the prognostic importance of right bundle branch block
      is unclear. We determined whether left and right bundle branch block was
      associated with all-cause mortality risk after adjustment for potential
      confounders, including clinical, exercise, and nuclear scintigraphic variables.
      SUBJECTS AND METHODS: We studied 7,073 adults who were referred for symptom
      limited nuclear exercise testing. Patients with heart failure or pacemakers were
      excluded. The presence or absence of bundle branch block was determined from
      resting electrocardiograms. The main outcome measure was all-cause mortality
      during a mean of 6.7 years of follow-up. RESULTS: One hundred ninety patients
      (3%) had complete right bundle branch block, and 150 (2%) had complete left
      bundle branch block. There were 825 deaths (12%). Mortality was greater in
      patients with complete right bundle branch block (24% [46 of 190]) or left bundle
      branch block (24% [36 of 150]) than in those without these findings (11% [779 of
      6,883 and 789 of 6,923, respectively]; both P <0.0001). After adjustment for
      potential confounders, right bundle branch block was as strong an independent
      predictor of mortality (hazard ratio [HR] 1.5; 95% confidence interval [CI]: 1.1
      to 2.1; P = 0.007) as left bundle branch block (HR 1.5; 95% CI: 1.0 to 2.0; P =
      0.017). Incomplete right bundle branch block was not associated with mortality.
      CONCLUSION: Complete right and left bundle branch block are independent
      predictors of all-cause mortality risk even after adjustment for exercise
      capacity, nuclear perfusion defects, and other risk factors.

PMID- 11239843
TI  - Outcomes of noncardiac surgery after coronary bypass surgery or coronary
      angioplasty in the Bypass Angioplasty Revascularization Investigation (BARI).
AB  - PURPOSE: Previous studies have shown that coronary artery bypass surgery reduces
      the risk of cardiac complications after noncardiac surgery. Whether coronary
      angioplasty provides equivalent protection is not known. SUBJECTS AND METHODS:
      Patients were randomly assigned to undergo cardiac artery bypass surgery or
      angioplasty as part of the Bypass Angioplasty Revascularization Investigation
      trial. All subsequent noncardiac surgeries during a mean (+/- SD) follow-up of
      7.7 years were recorded among participants in the ancillary Study of Economics
      and Quality of Life. Rates of mortality and nonfatal myocardial infarction,
      length of stay, and hospital costs were compared by the original randomized
      assignment. RESULTS: A total of 501 patients had noncardiac surgery at a median
      of 29 months after their most recent coronary revascularization procedure.
      Mortality and nonfatal myocardial infarction within 30 days of the first
      noncardiac surgery occurred in 4 of the 250 of the surgery-assigned patients and
      in 4 of the 251 of the angioplasty-assigned patients (P = 1.0). There were no
      significant differences in the mean length of hospital stay (6.3 +/- 6.7 versus
      6.2 +/- 6.8 days; P = 0.47) or hospital cost ($8,920 +/- $11,511 versus $7,785 +/
      $7,643; P = 0.33) between the surgery and angioplasty groups. Similar results
      were obtained when subsequent noncardiac procedures were included in the
      analysis. CONCLUSION: Rates of myocardial infarction and death after noncardiac
      surgery are similarly low after contemporary bypass surgery or angioplasty in
      patients with multivessel coronary artery disease.

PMID- 11239844
TI  - Time trends in the prevalence of atherosclerosis: a population-based autopsy
      study.
AB  - PURPOSE: Mortality from coronary heart disease is declining but little is known
      about trends in the prevalence of atherosclerosis. Autopsy rates in Olmsted
      County, Minnesota, are higher than the national average, offering an opportunity
      to address this matter. In this study, we determined the prevalence of anatomic
      coronary disease among autopsied Olmsted County residents and examined the
      generalizability of these findings. SUBJECTS AND METHODS: Reports of the 2,562
      autopsies performed between 1979 and 1994 on Olmsted County residents > or =20
      years of age were reviewed for the presence of coronary disease. RESULTS: Among
      autopsied decedents less than 60 years old at death and among coroner's cases,
      the prevalence of anatomic coronary disease declined with time (P for trend =
      0.05); no trend was detected among older persons or noncoroner's cases. By
      logistic regression analysis, the crude odds ratio ([OR] per 5 years) for the
      association between time and anatomic coronary disease was 0.94 (95% confidence
      interval [CI]: 0.86 to 1.03; P = 0.18]. Age, sex, and antemortem diagnosis of
      heart disease were also strongly related to the presence of disease. After
      adjustment for sex and antemortem diagnosis of heart disease, the prevalence of
      anatomic coronary disease decreased more in younger people than in older people
      (age 40 years: OR 0.43 [95% CI: 0.24 to 0.80]; age 60 years: OR 0.62 [95% CI:
      0.45 to 0.87]; age 80 years: OR 0.89 [95% CI: 0.64 to 1.23]). CONCLUSION: The
      prevalence of anatomic coronary disease at autopsy decreased between 1979 and
      1994, particularly among younger people, supporting the notion that the burden of
      coronary disease has shifted toward the elderly. These results suggest that the
      decreased incidence of coronary artery disease has contributed to the recent
      decrease in coronary mortality, particularly among younger people.

PMID- 11239845
TI  - The observation unit: a new interface between inpatient and outpatient care.
AB  - PURPOSE: Observation units for patients who present to emergency departments with
      chest pain have become common. We describe our 3-year experience with a
      multipurpose observation unit in which chest pain accounts for only a minority of
      patients' presenting clinical syndromes. SUBJECTS AND METHODS: We analyzed the
      effects of a 12-bed observation unit on inpatient admissions for common clinical
      syndromes, as well as its overall effects on inpatient medical admissions during
      its first 3 years of operation (1996 to 1998) compared with the 3 years preceding
      its creation (1993 to 1995). RESULTS: Among 7,507 patients admitted to the
      observation unit in 1996 to 1998, 6,334 (85%) were discharged home within 23
      hours. Total inpatient medical admissions fell by a similar number (n = 5,366)
      during the 3 years of operation of the observation unit when compared with the 3
      preceding years (39,569 admissions in 1996 to1998 versus 44,935 in 1993 to 1995).
      Analysis of local area trends suggested that the use of the observation unit
      contributed to reduced hospital admissions, rather than vice versa. CONCLUSION:
      Observation units can serve patients with diverse clinical syndromes and may
      reduce inpatient admissions. This novel "point of care" deserves further
      evaluation.

PMID- 11239847
TI  - Lymphedema.
AB  - Lymphedema is a set of pathologic conditions that are characterized by the
      regional accumulation of excessive amounts of interstitial protein-rich fluid.
      These occur as a result of an imbalance between the demand for lymphatic flow and
      the capacity of the lymphatic circulation. Lymphedema can result from either
      primary or acquired (secondary) disorders. In this review, the pathophysiology,
      classification, natural history, differential diagnosis, and treatment of
      lymphedema are discussed.

PMID- 11239846
TI  - Steroids in idiopathic pulmonary fibrosis: a prospective assessment of adverse
      reactions, response to therapy, and survival.
AB  - PURPOSE: We evaluated the risk and potential benefit of high-dose corticosteroid
      therapy in patients with idiopathic pulmonary fibrosis. SUBJECTS AND METHODS: We
      prospectively studied 41 patients with previously untreated, biopsy-proven
      idiopathic pulmonary fibrosis. Before treatment, we calculated clinical,
      radiographic, and physiologic severity-of-illness scores for each patient. We
      scored high-resolution computerized tomographic (CT) scans for ground glass and
      interstitial opacity. We determined the extent of cellular infiltration,
      interstitial fibrosis, desquamation, and granulation in open lung biopsy samples.
      Patients were monitored monthly for steroid-related side effects, response to
      therapy at 3 months, and mortality. RESULTS: All patients experienced at least
      one steroid-induced side effect. Eleven (27%) patients were nonresponders, 11
      (27%) were responders, and 19 (46%) remained stable. Of the 19 patients who died
      during a mean (+/- SD) follow-up of 3.3 +/- 2.3 years, 8 (42%) lost weight during
      the initial 3 months of steroid therapy; only 3 (14%) of the 22 patients still
      living (P = 0.08) experienced weight loss. In a multivariate analysis, greater
      fibrosis (hazard ratio [HR] = 1.4 per unit increase; 95% confidence interval
      [CI]: 1.0 to 1.9; P = 0.03) and cellularity (RR = 1.9 per unit increase; 95% CI:
      1.3 to 2.8; 3, P <0.001) in the biopsy sample and whether a patient was
      classified as a responder (RR = 0.4 versus nonresponder; 95% CI: 0.2 to 1.0; P =
      0.05) or stable (RR = 0.2 versus nonresponder; 95% CI: 0.1 to 0.6, P <0.001)
      after steroid therapy were associated with mortality. CONCLUSION: Corticosteroid
      treatment for idiopathic pulmonary fibrosis is associated with substantial
      morbidity. Patients who remain stable or respond to corticosteroid therapy have
      better survival than those who fail to respond. Whether this difference reflects
      an effect of treatment or less severe disease can be determined only in a
      randomized trial.

PMID- 11239848
TI  - Molecular biology of sodium channels and their role in cardiac arrhythmias.
AB  - The sodium channel is an integral membrane protein that plays a central role in
      conduction of the cardiac impulse in working cardiac myocytes and cells of the
      His-Purkinje system. The channel has two fundamental properties, ion conduction
      and gating. Specific domains of the channel protein control each of these
      functions. Ion conduction describes the mechanisms of the selective movement of
      sodium ion across the pore in the cell membrane. The selectivity of the channel
      for sodium ions is at least 10 times greater than that for other monovalent
      cations; the channel does not normally conduct divalent cations. Gating describes
      the opening and closing of the sodium channel pore. Sodium channels open
      transiently during membrane depolarization and close by a process termed
      inactivation. The cardiac sodium channel protein is a multimeric complex
      consisting of an alpha and an auxiliary beta-subunit. The genes encoding the
      sodium channel have been cloned and sequenced. The alpha subunit gene, SCN5A is
      sufficient to express a functional channel. However, beta subunit co-expression
      increases the level of channel expression and alters the voltage dependence of
      inactivation. Mutations of the sodium channel may result in incomplete
      inactivation during maintained depolarization, a decrease in the level of channel
      expression or acceleration of inactivation. The resulting clinical phenotypes
      include long QT syndrome, type III (LQT III), Brugada syndrome, and heart block.
      LQT III and Brugada syndromes have a high case fatality rate and are best treated
      with an implantable defibrillator.

PMID- 11239849
TI  - Effects of a practice guideline for community-acquired pneumonia in an outpatient
      setting.

PMID- 11239850
TI  - The benefits of, controversies surrounding, and professional recommendations for
      routine PSA testing: what do men believe?

PMID- 11239851
TI  - Familial periodic fever and amyloidosis due to a new mutation in the TNFRSF1A
      gene.

PMID- 11239854
TI  - Are right and left bundle branch block similarly associated with increased risk
      of mortality?

PMID- 11239855
TI  - Assessing and reducing cardiac risks of noncardiac surgery.

PMID- 11239856
TI  - Observation services--past, present, and future.

PMID- 11239858
TI  - Documentation guidelines: evolution, future direction, and compliance.

PMID- 11239857
TI  - Treatment of idiopathic pulmonary fibrosis: the rise and fall of corticosteroids.

PMID- 11239859
TI  - The effect of topical povidone-iodine, intraocular vancomycin, or both on aqueous
      humor cultures at the time of cataract surgery.
AB  - PURPOSE: To investigate whether the use of topical povidone-iodine before
      surgery, the addition of vancomycin to the irrigating solutions during
      phacoemulsification, or both reduces the frequency of positive intraocular
      cultures at the end of surgery. METHODS: A two-part, clinical study was
      performed. In the preliminary study, intracameral antibiotic concentrations were
      measured immediately after surgery (in 11 eyes) and 2 hours after surgery (in 11
      eyes) in patients treated with vancomycin. In the primary study, 400(1) patients
      were divided into four groups composed of 100 eyes each. The first and the second
      groups received vancomycin (20 microg/ml) in the irrigating fluid. The third and
      the fourth groups received irrigating fluid only without antibiotics. The first
      and third groups received a topical 5% povidone-iodine solution 10 and 5 minutes
      before surgery; a topical placebo solution was used in the second and the fourth
      groups. All patients in the primary study underwent anterior chamber aspiration
      after surgery, and culturing was performed 2 hours later. Identification and
      quantification of positive cultures in thioglycolate broth and chocolate agar
      were performed. RESULTS: In the preliminary study, the half-life of intraocular
      vancomycin was less than 2 hours. In the primary study, intraocular aspirates
      yielded positive cultures in two (2%), five (5%), 11 (11%), and 13 (13%)
      specimens from the first, second, third, and fourth groups, respectively.
      CONCLUSIONS: We found a lower rate of positive cultures in the group that
      received vancomycin in the irrigating fluid; 2 hours of contact between the
      antibiotic solution and bacteria produced results that reached statistical
      significance (P = 0.032).

PMID- 11239860
TI  - Glycemic control and lens transparency in patients with type 1 diabetes mellitus.
AB  - PURPOSE: To assess quantitatively the cumulative effect of hyperglycemia on lens
      transparency in patients with juvenile type 1 diabetes mellitus. METHODS:
      Subjects were 30 patients (30 eyes) with type 1 diabetes mellitus who had well
      documented records on the duration of diabetes mellitus and condition of glycemic
      control from the onset. They were 35 years of age or younger (mean, 26.0 years),
      had a history of type 1 diabetes mellitus at least 5 years (mean, 8.4 years), had
      corrected visual acuity of 20/20 or better, and showed no clinically apparent
      cataract on slit-lamp examination. Twenty-one eyes of 21 subjects served as age
      matched normal controls. They were 35 years of age or younger (mean, 25.7 years),
      had no diabetes mellitus, had corrected visual acuity of 20/20 or better, and
      showed no signs of cataract on slit-lamp examination. The degree of lens opacity
      was quantified using the anterior eye segment analysis system based on the
      Scheimpflug principle. An index was created to represent the cumulative effect of
      long-term glycemic control (hyperglycemic accumulation) by multiplying the
      average hemoglobin A(1c) value and the number of months from the onset. RESULTS:
      The patients with diabetes mellitus exhibited significantly greater degree of
      lens opacity than the normal controls (P =.017, Mann-Whitney U-test). Among the
      patients with diabetes mellitus, the lens opacity was greater in eyes with
      retinopathy than those without retinopathy (P =.011). Multiple regression
      analysis revealed that only the index of hyperglycemic accumulation significantly
      correlated with the degree of lens opacity (P =.042). CONCLUSION: Accumulated
      effect of hyperglycemia is related to the lens transparency in patients with
      diabetes.

PMID- 11239861
TI  - A description of human T-lymphotropic virus type I-related chronic interstitial
      keratitis in 20 patients.
AB  - OBJECTIVE: This study aimed to describe a syndrome that the authors call human T
      lymphotropic virus type I-related chronic interstitial keratitis. METHODS: A
      consecutive series of 194 human T-lymphotropic virus type I-infected patients
      (divided into 119 patients with human T-lymphotropic virus type I-associated
      myelopathy/tropical spastic paraparesis and 75 asymptomatic human T-lymphotropic
      virus type I carriers) was systematically examined. RESULTS: Twenty patients
      (10.3%) had bilateral anterior stromal lesions made up of approximately 10
      elevated, rounded or cloudy whitish opacities that were more or less confluent.
      The opacities were characteristically situated at the periphery of the anterior
      stroma, and the visual axis remained unaffected. The interstitial keratitis was
      chronic and unresponsive to topical administration of corticosteroids. It was
      mainly observed in patients affected by human T-lymphotropic virus type I
      associated myelopathy/tropical spastic paraparesis among whom there were 18 cases
      (15.1%), as opposed to two cases (2.7%) in asymptomatic carriers. CONCLUSION: A
      new cause of interstitial keratitis is reported. Human T-lymphotropic virus type
      I infection may have a much broader spectrum of ocular manifestations than
      previously described. As with the other manifestations of human T-lymphotropic
      virus type I infection, corneal lesions could be linked to a lymphoplasmocytic
      infiltration of the stroma leading to corneal opacities.

PMID- 11239862
TI  - New corneal findings in human T-cell lymphotrophic virus type 1 infection.
AB  - PURPOSE: Human T-cell lymphotrophic virus type 1 is a RNA retrovirus that
      primarily affects CD4+ T-cells. Human T-cell lymphotrophic virus type 1 infection
      is the established cause of adult T-cell leukemia/lymphoma, an aggressive
      malignancy of CD4+ T-cells, and two nonneoplastic conditions: human T-cell
      lymphotrophic virus type 1-associated myelopathy/tropical spastic paraparesis and
      human T-cell lymphotrophic virus type 1 uveitis. Other reported ophthalmic
      manifestations of human T-cell lymphotrophic virus type 1 infection include
      lymphomatous and leukemic infiltrates in the eye and ocular adnexa in patients
      with adult T-cell leukemia/lymphoma, retinal pigmentary degeneration, and neuro
      ophthalmic disorders in patients with human T-cell lymphotrophic virus type 1
      associated myelopathy/tropical spastic paraparesis and keratoconjunctivitis
      sicca, episcleritis, and sclerouveitis in asymptomatic human T-cell lymphotrophic
      virus type 1 carriers. This report describes the ocular findings in three
      Jamaican patients with human T-cell lymphotrophic virus type 1 infection and
      adult T-cell leukemia/lymphoma. METHODS: The clinical records of three patients
      with human T-cell lymphotrophic virus type 1 infection and adult T-cell
      leukemia/lymphoma examined at the National Eye Institute were reviewed. Each
      patient had one or more complete ophthalmic evaluations. RESULTS: All three
      patients had corneal abnormalities, including corneal haze and central opacities
      with thinning; bilateral immunoprotein keratopathy; and peripheral corneal
      thinning, scarring, and neovascularization. All three patients had elevated serum
      immunoglobulin levels. CONCLUSIONS: We believe that the novel corneal findings in
      these patients are most likely a consequence of the hypergammaglobulinemia
      induced by the human T-cell lymphotrophic virus type 1 infection or the T-cell
      malignancy.

PMID- 11239863
TI  - The effect of punctal occlusion on tear production, tear clearance, and ocular
      surface sensation in normal subjects.
AB  - PURPOSE: To evaluate the effect of temporary punctal occlusion on tear
      production, tear clearance, and ocular surface sensation in normal subjects.
      METHODS: Noncomparative interventional case series. Punctal occlusion with
      silicone punctal plugs was performed on nine normal subjects without complaints
      of ocular irritation and no known history of ocular surface disease. The lower
      punctum of both eyes was occluded in five subjects. The upper and lower puncta of
      only one eye were occluded in four subjects. Corneal and conjunctival sensations
      were measured with the Cochet-Bonnet anesthesiometer. Tear fluorescein clearance
      was evaluated with a CytoFluor II fluorophotometer by measuring the fluorescein
      concentration in minimally stimulated tear samples collected from the inferior
      tear meniscus 15 minutes after instillation of fluorescein. Schirmer test was
      performed without anesthesia. The tests were performed at days 0, 1, 3, 7, and 14
      to 17 after punctal occlusion. Relationships were analyzed with linear
      regressions, and a quadratic term was used to model a return to preocclusion
      levels. Paired t test was used to study the change in tear fluorescein
      concentration. RESULTS: In subjects who had the lower puncta of both eyes
      occluded, conjunctival sensation decreased in both eyes (right eye, P =.008; left
      eye, P =.003), but there was no change in corneal sensation. Their tear
      fluorescein clearance did not show a significant change from baseline (P =.90).
      However, a decrease in Schirmer test scores approached statistical significance
      (P =.056). In subjects with both puncta of only one eye occluded, we noted a
      decrease in corneal sensation (occluded eye, P =.042; nonoccluded eye, P =.036),
      conjunctival sensation (occluded, P =.001; nonoccluded, P =.060), and Schirmer
      scores (occluded, P =.022; nonoccluded, P =.011). Linear regression did not show
      a significant change in tear fluorescein clearance for either eye (occluded, P
      =.28; nonoccluded, P =.44). However, paired t test showed a significant worsening
      of tear clearance in the occluded eye from day 0 to day 3 (P =.001) followed by a
      subsequent improvement in tear clearance from day 3 to the end of the study
      period (P =.045). Paired t test did not reveal any significant changes in tear
      clearance in the nonoccluded eye. The quadratic term of the linear regression
      model demonstrated an increase toward preocclusion levels that approached
      statistical significance for corneal sensation (occluded, P =.053; nonoccluded, P
      =.099). It was statistically significant for conjunctival sensation (occluded, P
      =.001; nonoccluded, P =.045) and Schirmer scores (occluded, P =.047; nonoccluded,
      P =.044). CONCLUSIONS: Temporary punctal occlusion in normal subjects decreases
      tear production and ocular surface sensation. Our findings suggest that in
      addition to blocking tear drainage, punctal occlusion may affect the ocular
      surface/lacrimal gland interaction. These effects were more pronounced in
      subjects with both upper and lower puncta occluded. In normal subjects, there
      appears to be an autoregulatory mechanism to return tear production, tear
      clearance, and ocular surface sensation to preocclusion levels 14 to 17 days
      after punctal occlusion.

PMID- 11239864
TI  - Multilayered amniotic membrane transplantation for severe ulceration of the
      cornea and sclera.
AB  - PURPOSE: To examine the efficacy of amniotic membrane transplantation in the
      treatment of deep corneal and scleral ulcers. PATIENTS: A total of 11 patients
      were recruited for this study: four patients (four eyes) with corneal
      perforation, five patients (five eyes) with a deep corneal ulcer and
      descemetocele, and two patients (two eyes) with a scleral ulcer. METHODS: Ulcers
      were treated by amniotic membrane transplantation. Separate amniotic membranes
      were transplanted as material to fill the stromal layer (amniotic membrane
      filling), as a basement membrane (amniotic membrane graft), and as a wound cover
      (amniotic membrane patch). After surgery, all cases were treated with artificial
      tears, autologous serum drops, antibiotic eyedrops, topical corticosteroids, and
      sodium hyaluronate eyedrops. RESULTS: Eight eyes (72.7%) healed with
      epithelialization in 16.5 +/- 8.0 days (range, 7 to 29 days), with five and three
      eyes showing corneal epithelialization and conjunctival epithelialization,
      respectively. A persistent epithelial defect was noted in one eye with corneal
      ulcer after limbal allograft transplantation for a chemical burn and in two eyes
      with corneal ulcers as a complication of rheumatoid arthritis. CONCLUSION:
      Multilayered amniotic membrane transplantation may be effective for the treatment
      of deep ulceration of the cornea and sclera. In some eyes with total corneal
      limbal dysfunction or autoimmune disorders, amniotic membrane transplantation
      alone is not effective.

PMID- 11239865
TI  - Frequency doubling perimetry using a liquid crystal display.
AB  - PURPOSE: To compare frequency doubling contrast thresholds using a new liquid
      crystal window display with those obtained with the commercial video-based
      Frequency Doubling Technology perimeter. METHODS: One eye of 49 glaucoma patients
      and one eye of 49 normal controls were tested with the liquid crystal window and
      Frequency Doubling Technology systems. Both displays employed identical stimulus
      conditions and test strategies, although the dynamic range of the liquid crystal
      window-based display was approximately 30% smaller than that of the Frequency
      Doubling Technology system. Measurements were repeated using the video-based
      Frequency Doubling Technology perimeter in a subset of 21 eyes. Relationships
      between and within displays were assessed using a chance-corrected agreement
      measure (quadratic weighted kappa) and paired measurement differences.
      Variability was quantified using standard deviation from the mean paired
      measurement difference. RESULTS: Over the restricted operating range of the
      liquid crystal display system, between-display and within-video display
      variability was 2.3 dB and 3.2 dB, respectively, between-display agreement was
      0.66, and within-display agreement (test-retest for Frequency Doubling
      Technology) was 0.65. CONCLUSIONS: Levels of agreement and variability between
      the two frequency doubling displays were of similar magnitude to repeated (test
      retest) Frequency Doubling Technology measures, suggesting that contrast
      threshold measurements made using the two displays may be used interchangeably.
      However, the operating range of the current liquid crystal window-based display
      is smaller.

PMID- 11239866
TI  - Additive efficacy of unoprostone isopropyl 0.12% (rescula) to latanoprost 0.005%.
AB  - PURPOSE: To evaluate the safety and efficacy of adding unoprostone isopropyl
      0.12% vs placebo both given twice daily to latanoprost 0.005% given every
      evening. METHODS: We treated 41 patients with primary open-angle glaucoma or
      ocular hypertension with latanoprost 0.005% for 1 month and then randomized each
      to either placebo or unoprostone isopropyl 0.12% for 8 weeks. Diurnal intraocular
      pressures were measured at 08:00, 10:00, 12:00, 18:00, and 20:00 hours, both at
      baseline (time of randomization) and after 8 weeks of treatment. RESULTS: Twenty
      patients were treated in the placebo group and 21 in the unoprostone isopropyl
      group. After 8 weeks of treatment in the placebo group, the trough intraocular
      pressure at 08:00 and the diurnal pressure were 20.4 +/- 3.2 and 19.1 +/- 2.2 mm
      Hg, respectively. In the unoprostone isopropyl group the pressures were 19.4 +/-
      3.3 and 18.0 +/- 1.7 mm Hg (P =.22 and P =.042), respectively. However, eyes with
      a baseline pressure of 22 mm Hg or greater on latanoprost had an average 3.3 mm
      Hg greater reduction at trough (P <.01) and a 2.1 mm Hg greater decrease in
      diurnal pressure (P =.030) after adding unoprostone isopropyl (n = 14 eyes)
      compared with placebo (n = 16 eyes; P <.001). In addition, the range of the
      pressures throughout the diurnal curve was reduced from 2.7 mm Hg on latanoprost
      alone to 1.4 mm Hg after adding unoprostone isopropyl. Adverse events were
      similar between groups, and no patients were discontinued because of safety
      reasons. CONCLUSIONS: This study suggests that unoprostone isopropyl can safely
      improve the diurnal curve characteristics in patients who continue to have an
      elevated pressure on latanoprost 0.005% alone.

PMID- 11239867
TI  - Cytochrome P450 1B1 gene mutations in Japanese patients with primary congenital
      glaucoma(1).
AB  - PURPOSE: To report a novel missense mutation and DNA polymorphism of the
      CYP1B1gene in Japanese patients with primary congenital glaucoma. METHODS: A
      series of 11 unrelated patients with primary congenital glaucoma was examined.
      Patients were followed in the Kagoshima University Hospital between 1979 and
      1998. DNA was extracted from leukocytes of the patients, their families, and
      unrelated healthy individuals. Amplicons spanning the coding regions of the
      CYP1B1 gene were examined by direct sequencing and enzyme-restriction detection.
      RESULTS: In the 11 unrelated patients, besides the previously reported
      insertional mutation (1620 ins G), a novel missense mutation was identified at
      codons 444 to replace arginine with glutamine (R444Q) in one patient. The novel
      missense mutation cosegregated in the relevant family as an autosomal recessive
      pattern and was not found in other patients or control individuals. In addition,
      five polymorphic sites were found at codons 48, 119, 330, 432, and 449. These
      polymorphic alleles did not cosegregate with the disease, and they were found in
      healthy individuals as well. CONCLUSIONS: Approximately 20% of Japanese patients
      with primary congenital glaucoma may be affected by mutations in the CYP1B1 gene.
      Further studies are justified to explore whether a relationship exists between
      the phenotypic expressivity of the disease and the type of mutation.

PMID- 11239868
TI  - A follow-up study of Toxoplasma gondii infection in southern Brazil.
AB  - PURPOSE: To understand better the natural history of ocular toxoplasmosis by
      reexamining a well-characterized population in Southern Brazil. METHODS:
      Ophthalmological examination and serologic tests for Toxoplasma gondii infection
      were performed in 1997 on 383 individuals who had undergone the same evaluation
      in 1990. RESULTS: Of 109 seronegative subjects in 1990, 21 (19.3%) became
      seropositive by 1997, and 2 (1.5% of previously seronegative patients; 9.5% of
      those known to have seroconverted) developed ocular toxoplasmosis. Seroconversion
      occurred more frequently in individuals under 17 years of age (16 of 46 patients,
      34.8%) than in those greater than 17 years of age (5 of 63 patients, 7.9%; p =
      0.002). Of 131 seropositive individuals who did not have ocular lesions in 1990,
      11 (8.3%) had typical toxoplasmic lesions in 1997. Of the 13 individuals with non
      specific hyperpigmented small retinal lesions in 1990, 3 (23%) presented with
      typical lesions in 1997. CONCLUSIONS: Acquired T. gondii infection can result in
      late development of ocular lesions. Small, non-specific hyperpigmented retinal
      lesions may represent sites of T. gondii infection in seropositive individuals.

PMID- 11239869
TI  - Two families from New England with usher syndrome type IC with distinct
      haplotypes.
AB  - PURPOSE: To search for patients with Usher syndrome type IC among those with
      Usher syndrome type I who reside in New England. METHODS: Genotype analysis of
      microsatellite markers closely linked to the USH1C locus was done using the
      polymerase chain reaction. We compared the haplotype of our patients who were
      homozygous in the USH1C region with the haplotypes found in previously reported
      USH1C Acadian families who reside in southwestern Louisiana and from a single
      family residing in Lebanon. RESULTS: Of 46 unrelated cases of Usher syndrome type
      I residing in New England, two were homozygous at genetic markers in the USH1C
      region. Of these, one carried the Acadian USH1C haplotype and had Acadian
      ancestors (that is, from Nova Scotia) who did not participate in the 1755
      migration of Acadians to Louisiana. The second family had a haplotype that proved
      to be the same as that of a family with USH1C residing in Lebanon. Each of the
      two families had haplotypes distinct from the other. CONCLUSION: This is the
      first report that some patients residing in New England have Usher syndrome type
      IC. Patients with Usher syndrome type IC can have the Acadian haplotype or the
      Lebanese haplotype compatible with the idea that at least two independently
      arising pathogenic mutations have occurred in the yet-to-be identified USH1C
      gene.

PMID- 11239870
TI  - Modified transposition procedure of the vertical recti in sixth nerve palsy.
AB  - PURPOSE: To report a modified transposition procedure of the vertical recti for
      severely limited abduction of the globe caused by sixth nerve palsy and to
      compare this with the Hummelsheim transposition procedure. METHODS: Retrospective
      study of 13 eyes of 12 patients that had Hummelsheim transposition procedure and
      19 eyes of 17 patients that had modified transposition procedure of the vertical
      recti for severely limited abduction of the globe caused by sixth nerve palsy.
      The modified transposition procedure joins lateral strips of the vertical recti
      and sutures this junction to the lateral rectus muscle. Functional results of the
      Hummelsheim procedure are compared with functional results of the modified
      transposition procedure. RESULTS: Abductive capacity improved by 4.19 +/- 1.67 mm
      in the Hummelsheim group and 4.08 +/- 1.7 mm in the modification. The angle of
      squint changed from +22.33 +/- 6.74 degrees to -0.20 +/- 2.61 degrees in the
      Hummelsheim group and from +25.54 +/- 5.66 degrees to +0.95 +/- 5.26 degrees in
      the modification group. The functional results as to abductive capacity and
      postoperative angle of squint showed no significant difference between the two
      methods (P >.05, t test). The modification was less time consuming. CONCLUSIONS:
      A modification of the transposition techniques of eye muscles in sixth nerve
      palsy is introduced. Its functional results are comparable to the classic
      technique of Hummelsheim. Operative risk and trauma are reduced, because the
      technique avoids scleral stitches and was found to be less time consuming than
      the Hummelsheim procedure.

PMID- 11239871
TI  - Orbital venous-lymphatic malformations (lymphangiomas) mimicking cavernous
      hemangiomas.
AB  - PURPOSE: To illustrate that orbital venous-lymphatic malformations
      (lymphangiomas) may rarely simulate cavernous hemangiomas. METHODS: Retrospective
      case review. RESULTS: Five patients were identified from a series of 85 patients
      with venous-lymphatic malformations. The age range was 21 to 69 years, and all
      cases presented with a history of slowly progressive or long-standing proptosis.
      Computerized tomography revealed relatively homogeneous intraconal masses that
      were well defined anteriorly. Two of the cases had expansion of the orbit, and
      one had focal calcification. The three who had magnetic resonance imaging showed
      heterogeneous contrast enhancement. The preoperative diagnosis in every case was
      cavernous hemangioma, and intraoperatively the lesions resembled cavernous
      hemangiomas. However, posterior dissection was difficult in all patients because
      of dense adhesions and, in one case, led to a central retinal artery occlusion.
      The histology was characteristic of orbital venous-lymphatic malformations in all
      five cases. CONCLUSIONS: Deep orbital venous-lymphatic malformations presenting
      in adulthood may be rarely confused with cavernous hemangiomas. In doubtful
      cases, significant intralesional heterogeneity, best seen on magnetic resonance
      imaging, and focal calcification may help distinguish the two entities. This
      differentiation is important, because dissection of venous-lymphatic
      malformations is fraught with more complications than surgical excision of a
      cavernous hemangioma.

PMID- 11239872
TI  - Vancomycin prophylaxis and emerging resistance: are ophthalmologists the
      villains? The heroes?
AB  - PURPOSE: To determine whether the routine use of vancomycin prophylaxis in
      elective cataract surgery promotes emerging resistance and provides effective
      protection against post-operative endophthalmitis. METHODS: Critical review of
      the current scientific and clinical literature was undertaken including
      appropriate statistical analyses of published data. RESULTS: Public health
      concerns for emergent vancomycin-resistant life-threatening "super bugs" are
      legitimate. Evaluation of the risk factors that are known to promote emerging
      vancomycin resistance (sick patients, hospital intensive care unit setting,
      methicillin-resistant Staphylococcus aureus (MRSA) clonal infections, prolonged
      systemic therapy, sub-therapeutic dosing, indwelling intravascular and drainage
      catheters, total kilogram usage and agricultural use) suggest that ophthalmic
      usage in routine cataract surgery is unlikely to be a significant factor in
      promoting emerging worldwide resistance. Clinical and scientific studies
      purporting to prove the value of vancomycin prophylaxis in cataract surgery
      contain substantial biases and design flaws that seriously undermine their
      validity. Issues of potential intraocular toxicity, increased costs, absence of
      medical-legal protection, and compliance with current Centers for Disease Control
      and Prevention (CDC) and American Academy of Ophthalmology guidelines (in
      hospital) mitigate against this practice. CONCLUSIONS: Ophthalmologists who use
      vancomycin prophylaxis in routine cataract surgery are neither the villains nor
      heroes according to my interpretation of the currently available scientific data.
      Personal conscience and an ongoing critical review of the literature should guide
      each ophthalmologist's choice in this controversy.

PMID- 11239873
TI  - Microkeratome-based limbal harvester for limbal stem cell transplantation:
      preliminary studies.
AB  - PURPOSE: To develop a mechanical device to perform limbal transplantation. This
      procedure is a valuable surgical technique for management of limbal stem cell
      deficiency. However, the freehand dissection to obtain donor tissue is laborious
      and time-consuming. METHODS: A manual microkeratome (LSK One; Moria/Microtech,
      Doylestown, Pennsylvania) using a redesigned head (200 microm thickness, 16-mm
      blade) was used to create partial thickness corneoscleral caps from human donor
      globes. RESULTS: Corneoscleral caps obtained from human donor globes included a
      ring of approximately 1 mm of perilimbal sclera in contiguity to the cornea.
      Scanning electron microscopy showed a smooth cut surface with some chatter at the
      margins. CONCLUSION: This instrument ensures an effective and straightforward
      method to dissect the area where stem cells have been indirectly localized.

PMID- 11239874
TI  - Resolution of microsporidial keratoconjunctivitis in an AIDS patient treated with
      highly active antiretroviral therapy.
AB  - PURPOSE: To report the outcome of microsporidial keratoconjunctivitis in a
      patient with acquired immunodeficiency syndrome (AIDS) after highly active
      antiretroviral therapy without any specific treatment for microsporidiosis.
      METHODS: Case report. A 42-year-old woman diagnosed with AIDS and severe
      immunodepression (CD4+ of 9 cells/mm(3) and viral load of 460,000/mm(3)),
      antiretroviral naive, presented with cerebral toxoplasmosis and microsporidial
      keratoconjunctivitis in the right eye documented by conjunctival scraping and
      electron microscopy. RESULTS: The patient was treated with a combination of
      indinavir, stavudine, and lamivudine, besides sulfadiazine and pyrimethamine. No
      specific treatment for the microsporidial keratoconjunctivitis was attempted. One
      month later, the keratoconjunctivitis had disappeared. CONCLUSION: This case
      suggests that microsporidial keratoconjunctivitis in the setting of AIDS and
      severe immunodepression can be effectively managed with highly active
      antiretroviral therapy alone.

PMID- 11239875
TI  - Gastric signet ring cell adenocarcinoma metastatic to the iris.
AB  - PURPOSE: To report a case of gastric signet ring cell adenocarcinoma metastatic
      to the iris. METHODS: Case report. A 38-year-old man with a history of gastric
      signet ring cell adenocarcinoma presented with a white lacework-like mass on the
      iris of the left eye. RESULTS: Systemic medical evaluation demonstrated no other
      metastasis. Because of increased intraocular pressure, trabeculectomy and
      peripheral iridectomy were performed. Histology of the iris specimen demonstrated
      metastasis of gastric signet ring cell adenocarcinoma to the iris. CONCLUSION:
      Gastric signet ring cell carcinoma can metastasize to the iris. Ophthalmologists
      should include this possibility in the differential diagnosis when encountering a
      patient with a history of gastric adenocarcinoma and an iris mass.

PMID- 11239876
TI  - Conjunctival T-cell lymphoma caused by human T-cell lymphotrophic virus
      infection.
AB  - PURPOSE: To examine the cause of adult T-cell leukemia/lymphoma. METHODS: We
      examined a conjunctival biopsy from a 29-year-old Jamaican man who developed
      bilateral conjunctival masses. Adult T-cell leukemia/lymphoma was diagnosed using
      routine histology, immunohistochemistry, electron microscopy, microdissection,
      and the polymerase chain reaction. RESULTS: Histopathologic examination revealed
      a conjunctival lymphoma. Clonality of the T-cell receptor gamma gene and human T
      cell lymphotrophic virus gag gene were detected in the malignant cells. The
      demonstration of the human T-cell lymphotrophic virus gene and the rearrangement
      of the T-cell receptor gene in this neoplasm provide proof that human T-cell
      lymphotrophic virus is the cause of this conjunctival T-cell lymphoma.
      CONCLUSION: Human T-cell lymphotrophic virus is the cause of adult T-cell
      leukemia/lymphoma, an aggressive malignancy of CD4+ lymphocytes.

PMID- 11239877
TI  - Horner syndrome associated with implantation of a vagus nerve stimulator.
AB  - PURPOSE: To report a case of Horner syndrome that occurred after implantation of
      a vagus nerve stimulator. METHODS: Case report. RESULTS: A 6-year-old female with
      cerebral dysgenesis and intractable partial seizures presented with Horner
      syndrome after vagus nerve stimulator implantation. CONCLUSION: Horner syndrome
      can occur as a result of the vagus nerve stimulator implant procedure and should
      be included as one of its possible surgical complications.

PMID- 11239878
TI  - Serous retinal detachment and cystoid macular edema in hypotony maculopathy.
AB  - PURPOSE: To report the foveal structural findings of hypotony maculopathy imaged
      with optical coherence tomography. METHODS: Case report of a 39-year-old white
      woman with a 20 year history of uveitis, who underwent pars plana vitrectomy and
      pars plana Baerveldt implant for intractable glaucoma. Four months
      postoperatively, decreased vision and hypotony maculopathy ensued. Optical
      coherence tomographic (OCT) images were taken horizontally through the macula.
      RESULTS: OCT demonstrated large intraretinal cysts, serous macular detachment,
      and choroidal folds, which resolved upon resolution of hypotony. CONCLUSION:
      Cystic macular changes and serous macular detachment can be prominent features of
      hypotony maculopathy.

PMID- 11239879
TI  - Tamoxifen retinopathy in a male patient.
AB  - PURPOSE: To report a case of tamoxifen retinopathy in a male patient. METHODS:
      Case report. A 68-year-old man, who had received a cumulative tamoxifen dose of
      60 g over 33 months for unresectable hepatocellular carcinoma, was evaluated.
      RESULTS: A peculiar, bilateral, symmetric, inner retinal crystalline deposition
      associated with mild macular edema was discovered. No other ocular toxicity of
      tamoxifen was observed. CONCLUSION: To our knowledge, this is the first report of
      tamoxifen retinopathy in a male.

PMID- 11239880
TI  - Indocyanine green selectively stains the internal limiting membrane.
AB  - PURPOSE: To demonstrate whether indocyanine green stains the inner limiting
      membrane of the retina or residual vitreous cortex. METHODS: We report on the
      intraoperative staining patterns of the vitreomacular interface in 10 eyes of 10
      consecutive patients who underwent vitrectomy with indocyanine green staining for
      macular hole formation and diffuse diabetic macular edema. RESULTS: In five eyes
      of five patients with macular holes, indocyanine green staining of the macula
      after posterior vitreous detachment resulted in an immediate visibility of a
      discernable membrane that was not previously seen. In five eyes of five patients
      with diffuse diabetic macular edema and adherent cortical vitreous, indocyanine
      green failed to stain the vitreomacular interface. After peeling off the residual
      vitreous cortex, however, a discernable membrane could be identified using
      indocyanine green dye again. Light and transmission electron microscopy revealed
      the inner limiting membrane as the membrane that had been stained and removed in
      all specimens. CONCLUSION: Indocyanine green selectively stains the inner
      limiting membrane. Staining of the vitreomacular interface using indocyanine
      green as a vital dye enables the surgeon to distinguish between the residual
      vitreous cortex and the inner limiting membrane, and it allows safer and easier
      removal of the inner limiting membrane.

PMID- 11239881
TI  - Indocyanine green facilitates removal of epiretinal and internal limiting
      membranes in myopic eyes with retinal detachment.
AB  - PURPOSE: To describe the use of intravitreal indocyanine green as an aid to
      identifying epiretinal membranes and internal-limiting membranes during surgery
      for a retinal detachment resulting from a macular hole. METHODS: A 62-year-old
      man who had a retinal detachment resulting from a macular hole underwent
      vitrectomy. During the surgery, intravitreal indocyanine green was injected
      intravitreally. RESULTS: The internal-limiting membrane was stained green, but
      the epiretinal membrane was unstained. Because the epiretinal membrane and
      internal-limiting membrane were clearly identified, they could be completely
      removed. The clinical observations of the epiretinal membrane and internal
      limiting membrane excised were confirmed by electron microscopy. Successful
      reattachment was obtained without damage to the retina. CONCLUSION: Removal of
      epiretinal membrane and internal-limiting membrane can be facilitated by using
      intravitreal indocyanine green during vitrectomy. We recommend further studies to
      confirm the benefit of this technique.

PMID- 11239882
TI  - Macular translocation for subfoveal choroidal neovascularization in angioid
      streaks.
AB  - PURPOSE: To report a case of visual improvement after macular translocation
      performed for a subfoveal choroidal neovascular membrane in a patient with
      pseudoxanthoma elasticum and angioid streaks. METHODS: The fovea was translocated
      inferiorly by scleral imbrication, intentional retinal detachment with a small
      posterior retinotomy, and partial fluid-air exchange. The choroidal neovascular
      membrane was photocoagulated 1 week later. RESULTS: The visual acuity of the
      patient improved from 20/125 to 20/40. The center of the foveal avascular zone
      was moved inferiorly 844 microm. The choroidal neovascular membrane was
      extrafoveal after translocation and was treated with laser photocoagulation.
      CONCLUSION: Macular translocation may be considered in the management of
      subfoveal choroidal neovascular membrane in patients with pseudoxanthoma
      elasticum and angioid streaks.

PMID- 11239883
TI  - Silicone oil-associated optic nerve degeneration.
AB  - PURPOSE: To report the frequency and extent of silicone oil migration into the
      optic nerve during silicone oil endotamponade. METHODS: Histopathologic analysis
      of 74 eyes enucleated after silicone oil endotamponade. RESULTS: In 14 of 74
      enucleated eyes (24%), optically empty vacuoles regarded as silicone oil vacuoles
      were observed in the retrolaminar optic nerve. In three eyes, silicone oil in the
      optic nerve was surrounded by a granulomatous inflammatory reaction. In serial
      cross sections, the vacuoles extended up to the line of surgical transsection (up
      to 9 mm) of the optic nerve and constituted up to 40% of the total cross
      sectional area. CONCLUSIONS: After silicone oil endotamponade, silicone oil may
      replace a considerable amount of tissue of the retrolaminar optic nerve. A
      granulomatous inflammatory reaction surrounding silicone oil may add to optic
      nerve damage.

PMID- 11239884
TI  - Frosted branch angiitis in a child with HIV infection.
AB  - PURPOSE: In adults with human immunodeficiency virus (HIV) infection, frosted
      branch angiitis is commonly associated with cytomegalovirus retinitis and
      responds to anti-cytomegalovirus therapy. We describe the first pediatric case of
      HIV-associated frosted branch angiitis. METHODS: Case report. RESULTS: A 7-year
      old HIV-infected male with frosted branch angiitis was refractory to induction
      doses of intravenous ganciclovir and foscarnet over a 2-month period. Although
      cytomegalovirus antigenemia resolved, the angiitis only improved after subsequent
      treatment with systemic corticosteroids. CONCLUSION: Frosted branch angiitis in
      this patient was not attributed to cytomegalovirus. The pathogenesis of HIV
      associated frosted branch angiitis may differ between children and adults.

PMID- 11239885
TI  - High-dose intravitreal ganciclovir and foscarnet for cytomegalovirus retinitis.
AB  - PURPOSE: To describe the chronic use of high doses of intravitreal ganciclovir,
      in combination with foscarnet, for the treatment of cytomegalovirus retinitis.
      METHODS: A 31-year-old man with human immunodeficiency virus (HIV) infection and
      unilateral active cytomegalovirus retinitis was treated with escalating
      intravitreal injections of ganciclovir (up to 3.0 mg twice a week) in combination
      with foscarnet (up to 2.4 mg twice a week) over the course of approximately 1
      year. RESULTS: Complete regression of the retinitis was obtained with high doses
      of intravitreal ganciclovir and foscarnet. Visual acuity in the affected eye
      remained 20/20 throughout the course of therapy. No ganciclovir retinal toxicity
      was identified. CONCLUSION: High doses of intravitreal ganciclovir in combination
      with foscarnet can be well tolerated and may be required to successfully control
      cytomegalovirus retinitis in some patients.

PMID- 11239886
TI  - Bilateral optic nerve atrophy in myotonic dystrophy.
AB  - PURPOSE: To document a case of bilateral optic atrophy in a patient with myotonic
      dystrophy. Myotonic dystrophy is an autosomal dominant disorder, genetically
      resulting from an expansion of an unstable CTG repeat in the 3'-untranslated
      region of a protein kinase gene (DMPK) on chromosome 19q13.3. METHODS: Case
      report, clinical examination, fundus photographs, visual fields, visual evoked
      potentials, electroretinograms, and genetic studies of a 56-year-old woman
      clinically diagnosed with myotonic dystrophy. RESULTS: The patient experienced
      decreased vision consisting of light perception with the right eye and 20/25 with
      the left. Fundus examination showed bilateral pallor of the optic disks.
      Intraocular pressure was normal. Visual field testing, visual evoked potentials,
      and electroretinogram were abnormal. A pathologic CTG expansion in the myotonic
      dystrophy gene was found. CONCLUSIONS: In a patient with myotonic dystrophy,
      confirmed with genetic molecular diagnosis, bilateral optic atrophy was present.
      Optic atrophy should be considered a possible complication of myotonic dystrophy.

PMID- 11239887
TI  - Ectopic chordoma with orbital invasion.
AB  - PURPOSE: To report a rare ectopic chordoma within the orbital wall. METHODS: Case
      report. RESULTS: A 63-year-old woman developed swelling of the eyelid, tearing,
      blurred vision, and progressive proptosis RE of 1 month's duration. Neuroimaging
      studies revealed an osteolytic mass with epicenter at the sphenozygomatic suture
      that eroded intracranially, invaded into the orbit, and compressed orbital soft
      tissues. Surgical debulking was done followed by radiation treatment. The
      pathologic findings of physaliphorous epithelial cells with multiple vacuoles
      containing mucin, prominent nuclei, and positive immunohistochemical staining for
      S-100, Vimentin, epithelial membrane antigen, and pancytokeratin were diagnostic
      for chordoma. CONCLUSION: Orbital wall ectopic localization of a chordoma distant
      from the clivus is a rare occurrence.

PMID- 11239888
TI  - Effect of corneal polarization axis on assessment of retinal nerve fiber layer
      thickness by scanning laser polarimetry.

PMID- 11239901
TI  - Amygdala response to facial expressions in children and adults.
AB  - BACKGROUND: The amygdala plays a central role in the human response to affective
      or emotionally charged stimuli, particularly fear-producing stimuli. We examined
      the specificity of the amygdala response to facial expressions in adults and
      children. METHODS: Six adults and 12 children were scanned in a 1.5-T scanner
      during passive viewing of fearful and neutral faces using an EPI BOLD sequence.
      All scans were registered to a reference brain, and analyses of variance were
      conducted on the pooled data to examine interactions with age and gender.
      RESULTS: Overall, we observed predominantly left amygdala and substantia
      innominata activity during the presentation of nonmasked fearful faces relative
      to fixation, and a decrease in activation in these regions with repeated exposure
      to the faces. Adults showed increased left amygdala activity for fearful faces
      relative to neutral faces. This pattern was not observed in the children who
      showed greater amygdala activity with neutral faces than with fearful faces. For
      the children, there was an interaction of gender and condition whereby boys but
      not girls showed less activity with repeated exposure to the fearful faces.
      CONCLUSIONS: This is the first study to examine developmental differences in the
      amygdala response to facial expressions using functional magnetic resonance
      imaging.

PMID- 11239902
TI  - Noradrenergic dysfunction in the prefrontal cortex in depression: an [15O] H2O
      PET study of the neuromodulatory effects of clonidine.
AB  - BACKGROUND: Noradrenergic dysfunction has been consistently implicated in
      depression. Much of the evidence, though, has been indirect, such as an
      attenuated growth hormone response to the alpha2-adrenoceptor agonist clonidine.
      To more directly examine central functioning of the noradrenergic system in
      depression, we have used [15O] H2O positron emission tomography (PET) to measure
      cerebral blood flow (rCBF) in combination with clonidine as a neuromodulatory
      probe. METHODS: Subjects were six depressed and six healthy women, medication
      free and matched for age and phase of menstrual cycle. Two PET scans were
      acquired at baseline and two scans at 20 and 35 min following an intravenous
      clonidine infusion of 1.4 microg/kg while subjects performed a sustained
      attention task. RESULTS: The growth hormone response did not show a significant
      difference between groups. However, PET results revealed a difference in the
      right superior prefrontal cortex that was resolved as an interaction from
      decreased rCBF in healthy control subjects but increased rCBF in the depressed
      group, which was not accounted for by differences in task performance.
      CONCLUSIONS: This differential effect of clonidine in the right prefrontal cortex
      provides in vivo evidence of noradrenergic dysfunction in depression, which we
      postulate arises from functionally impaired presynaptic alpha2-adrenoceptors as
      well as regionally "supersensitive" postsynaptic cortical alpha2-adrenoceptors.

PMID- 11239903
TI  - [123I] beta-CIT and single photon emission computed tomography reveal reduced
      brain serotonin transporter availability in bulimia nervosa.
AB  - BACKGROUND: Impaired serotonin transmission has been implicated in the
      pathophysiology of eating disorders. We investigated the in vivo availability of
      brain serotonin transporters and dopamine transporters in bulimia nervosa
      patients. METHODS: Approximately 24 hours after injection of [123I]-2beta
      carbomethoxy-3beta-(4-iodophenyl)tropane ([123I] beta-CIT), single photon
      emission computed tomography scans were performed in 10 medication-free, female
      bulimic patients and 10 age-matched, healthy females. For quantification of brain
      serotonin transporter and dopamine transporter availability, a ratio of specific
      to nonspecific [123I] beta-CIT brain binding was used (V(3)" = target region -
      cerebellum/cerebellum). RESULTS: Drug-free bulimia nervosa patients showed a 17%
      reduced brain serotonin transporter availability in the hypothalamus and
      thalamus, as compared with healthy control subjects (2.4 +/- 0.4 vs. 2.9 +/- 0.4,
      p =.026), and a similar reduction in striatal dopamine transporter availability.
      There was a negative correlation of illness duration and serotonin transporter
      availability (r = -.65; p =.042) and a strong positive correlation between
      hypothalamic/thalamic and striatal V(3)" (r =.80, p <.001). CONCLUSIONS: This
      first report of reduced [123I] beta-CIT binding in a relatively small group of
      patients with bulimia nervosa suggests a reduced hypothalamic and thalamic
      serotonin transporter availability in bulimia, which is more pronounced with
      longer duration of illness.

PMID- 11239904
TI  - Haplotype study of three polymorphisms at the dopamine transporter locus confirm
      linkage to attention-deficit/hyperactivity disorder.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is often treated
      using methylphenidate, a psychostimulant that inhibits the dopamine transporter.
      This led E.H. Cook and colleagues to consider the dopamine transporter locus
      (DAT1) as a primary candidate gene for ADHD. That group reported a significant
      association between ADHD and the 480-base pair (bp) allele of the variable number
      of tandem repeats (VNTR) polymorphism located in the 3' untranslated region of
      the DAT1 gene. This association was later replicated in additional studies.
      METHODS: The DAT1 gene has additional common polymorphisms in intron 9 and exon
      9. We investigated the possibility of linkage of DAT1 and ADHD using the VNTR
      polymorphism and two additional common polymorphisms in 102 nuclear families with
      an ADHD proband. Using the transmission disequilibrium test, we examined the
      transmission of the alleles of each of these polymorphisms, as well as the
      haplotypes of the polymorphisms. RESULTS: We did not observe significant evidence
      for the biased transmission of the alleles of either the VNTR or the additional
      two polymorphisms when examined individually, although there was a trend for the
      biased transmission of the 480-bp allele of the VNTR. When we examined the
      haplotypes of the three polymorphisms we found significant evidence for biased
      transmission of one of the haplotypes containing the 480-bp VNTR allele. We also
      genotyped six additional DNA sequence variants of the DAT1 gene. However, these
      variants were not sufficiently polymorphic in our sample to be informative. Two
      of the DNA variants that result in an amino acid change, Ala559Val and Glu602Gly,
      were not observed in our sample. CONCLUSIONS: Our results support previous
      findings of an association between the DAT1 gene and ADHD.

PMID- 11239905
TI  - Drugs used in the treatment of attention-deficit/hyperactivity disorder affect
      postsynaptic firing rate and oscillation without preferential dopamine
      autoreceptor action.
AB  - BACKGROUND: Current theories propose that low doses of catecholaminergic
      stimulants reduce symptoms in patients with attention-deficit/hyperactivity
      disorder by acting on autoreceptors to reduce catecholaminergic transmission; few
      data are available that directly address this hypothesis. METHODS: We
      investigated the autoreceptor and postsynaptic receptor actions of systemically
      administered stimulants on dopaminergic systems in rats with single-unit
      recording in the substantia nigra pars compacta and globus pallidus,
      respectively. RESULTS: Dose-response curves for rate indicated that the potencies
      of the indirect-acting agonists methylphenidate and D-amphetamine at dopaminergic
      autoreceptors were not greater than at postsynaptic receptors; in fact, D
      amphetamine was more potent postsynaptically. In addition to effects on firing
      rate, spectral/wavelet analyses indicated that these drugs had prominent effects
      on postsynaptic multisecond oscillations. These oscillations were shifted by
      stimulants from baseline periods of approximately 30 sec to periods of 5-10 sec.
      Effects on pattern were found at doses as low as 1.0 mg/kg (methylphenidate) and
      0.2 mg/kg (D-amphetamine). At this latter dose, D-amphetamine had little effect
      presynaptically. CONCLUSIONS: These and prior results demonstrate that there is
      no autoreceptor-preferring dose range of catecholaminergic stimulants; these
      drugs at low doses are unlikely to reduce motor activity by this mechanism.
      Nonetheless, they might affect attentive and cognitive processes by modulating
      multisecond temporal patterns of central activity.

PMID- 11239906
TI  - Chronic cold exposure potentiates CRH-evoked increases in electrophysiologic
      activity of locus coeruleus neurons.
AB  - BACKGROUND: Chronic stress exposure can produce sensitization of norepinephrine
      release in the forebrain in response to subsequent stressors. Furthermore, the
      increase in norepinephrine release in response to the stress-related peptide
      corticotropin-releasing hormone (CRH) is potentiated by prior chronic stress
      exposure. To explore possible mechanisms underlying these alterations in
      norepinephrine release, we examined the effect of chronic stress on the
      electrophysiologic activity of locus coeruleus (LC) neurons in response to
      centrally applied CRH. METHODS: Single-unit recordings of LC neurons in halothane
      anesthetized rats were used to compare the effect of intraventricular
      administration of CRH (0.3-3.0 microg) in control and previously cold-exposed (2
      weeks at 5 degrees C) rats. RESULTS: The CRH-evoked increase in LC neuron
      activity was enhanced following chronic cold exposure, without alteration in
      basal activity of LC neurons. The enhanced CRH-evoked activation was apparent at
      higher doses of CRH but not at lower ones, resulting in an increased slope of the
      dose-response curve for CRH in previously cold-exposed rats. CONCLUSIONS: These
      data, in combination with previous data, suggest that the sensitivity of LC
      neurons to excitatory inputs is increased following chronic cold exposure. The
      altered functional capacity of LC neurons in rats after continuous cold exposure
      may represent an experimental model to examine the role of central noradrenergic
      neurons in anxiety and mood disorders.

PMID- 11239907
TI  - Reactivity of serotonin in whole blood: relationship with drug response in
      obsessive-compulsive disorder.
AB  - BACKGROUND: Obsessive-compulsive disorder responds almost only to potent
      serotonin reuptake inhibitors. Previous studies have suggested a relation between
      serotonergic function and clinical outcome in serotonin reuptake inhibitor
      treatment of obsessive-compulsive disorder. METHODS: In a randomized, double
      blind trial, comparing clomipramine, paroxetine, and a placebo in obsessive
      compulsive disorder, serotonin levels in whole blood (WB-5-HT) were measured at
      baseline, after 1 week, and after 4 weeks of treatment and related to clinical
      outcome in 36 patients. RESULTS: In patients treated with serotonin reuptake
      inhibitors there was a pronounced decrease of WB-5-HT, variable after 1 week and
      uniformly maximal after 4 weeks. The decrease of WB-5-HT after 1 week of
      serotonin reuptake inhibitor treatment correlated negatively with clinical
      outcome after 12 weeks (r = -.61, p =.0006); hence, patients with slower WB-5-HT
      reactivity eventually responded better to treatment. Baseline WB-5-HT, but not WB
      5-HT reactivity, was related to season. Depression, autistic traits, and previous
      serotonin reuptake inhibitor treatment predicted nonresponse. CONCLUSIONS: A fast
      decrease of WB-5-HT was associated with poor clinical outcome. This may be
      related to faster serotonin efflux from platelets, which has previously been
      linked to autism. Further studies are necessary to identify the underlying
      mechanism and discern whether serotonin reuptake inhibitor-induced WB-5-HT
      decrease is clinically useful.

PMID- 11239908
TI  - Elevated motor threshold in drug-free, cocaine-dependent patients assessed with
      transcranial magnetic stimulation.
AB  - BACKGROUND: Transcranial magnetic stimulation (TMS) provides a noninvasive method
      of examining cortical inhibitory and excitatory processes and cortical
      excitability in awake subjects. There is evidence from clinical and
      electroencephalographic (EEG) data that cortical excitability may be abnormal in
      some psychiatric populations. Chronic cocaine abuse influences a number of
      neurotransmitters that are involved in the excitatory/inhibitory balance of the
      cerebral cortex. This pilot study was conducted to ascertain the possible utility
      of TMS in examining cortical excitability in a population of chronic cocaine
      abusers. METHODS: The right and left motor thresholds of ten cocaine-dependent
      subjects, according to DSM-IV, and ten normal control subjects were examined
      using single pulse TMS. RESULTS: The resting motor thresholds resulting from
      stimulation of the right or the left motor cortical regions were significantly
      elevated in cocaine-dependent subjects compared with matched control subjects.
      CONCLUSIONS: These pilot data suggest that chronic cocaine use significantly
      alters cortical excitability in the direction of increased inhibition or
      decreased excitability. We hypothesize that this observation reflects adaptation
      to those effects of cocaine intoxication that promote cortical excitability and
      seizures.

PMID- 11239909
TI  - Translating the basic and clinical cognitive neuroscience of schizophrenia to
      drug development and clinical trials of antipsychotic medications.
AB  - Neurocognitive deficits have become increasingly important defining features of
      schizophrenia and its treatment. Multiple domains of neurocognitive functions are
      impaired in schizophrenia patients, and these impairments are considered to be
      core features of the disorder. Many recent reports support the importance of the
      relationship of these neurocognitive deficits to measures of "functional outcome"
      such as social skills acquisition, social problem solving, and community outcome.
      Neurocognitive deficits appear to be improved with newer (atypical) antipsychotic
      medications across a broad range of domains in schizophrenia patients. Together
      with clinical neuroscience advances, basic research in cognitive neuroscience
      ranging from animal models of gating functions to early gene expression induced
      by antipsychotic medications has illuminated the specific neural basis of
      neurocognitive deficits in schizophrenia and the neurobiology of antipsychotic
      actions. These translational basic and clinical studies provide powerful
      screening tools and strategies for drug development and the subsequent assessment
      of the clinical efficacy of new antipsychotic medications. These interlocking
      clinical and basic research findings have substantial implications for improving
      both drug development and improving clinical trials methodology for antipsychotic
      medications. Thus, there is an informed translation and cross-fertilization
      between basic and clinical research focused on the development and assessment of
      putative new antipsychotic compounds.

PMID- 11239910
TI  - Sexually dimorphic relationship of a 5-HT2A promoter polymorphism with obsessive
      compulsive disorder.
AB  - BACKGROUND: In an earlier analysis of 73 subjects from this study, the reduced
      activity catechol O-methyltransferase variant was shown to be associated with
      obsessive-compulsive disorder in men only. We hypothesized that the 5-HT2A
      promoter polymorphism, -1438G>A, previously associated with anorexia nervosa,
      would be more abundant in women with obsessive-compulsive disorder. METHODS: One
      hundred and one Caucasian obsessive-compulsive disorder patients (48 women, 53
      men) and 138 control subjects (77 women, 61 men), were genotyped. DSM-III-R
      psychiatric diagnoses were assigned based on the SCID-I. RESULTS: As
      hypothesized, the -1438A allele frequency was higher in obsessive-compulsive
      disorder women (.57) than female control subjects (.42) (p =.015). The genotype
      frequencies were also significantly different (p =.020). Allele frequencies did
      not differ between male obsessive-compulsive disorder patients (.44) and male
      control subjects (.41). CCONSLUSIONS: We have found that a 5-HT2A promoter
      polymorphism is associated with obsessive-compulsive disorder in women but not in
      men, strengthening the argument that there may be fundamental gender differences
      in the genetic susceptibility to obsessive-compulsive disorder.

PMID- 11239911
TI  - 5-Hydroxytryptamine and atropine inhibit nicotinic receptors in submucosal
      neurons.
AB  - The whole-cell recording technique was used to investigate the pharmacological
      properties of acetylcholine-activated ion channels of cultured submucosal neurons
      from guinea-pig small intestine. Acetylcholine induced whole-cell membrane
      currents (I(ACh)) in a concentration-dependent manner (EC(50)=79 microM). I(ACh)
      exhibited strong inward rectification, had a reversal potential of +19+/-2 mV
      (Na(+) outside, Cs(+) inside), was reversibly inhibited in a concentration
      dependent manner by hexamethonium (EC(50)=5 microM) and atropine (EC(50)=1.6
      microM), and was unaffected by alpha-bungarotoxin (30 nM). Atropine was less
      potent in inhibiting the currents induced by 30 microM acetylcholine than those
      induced by 1 mM acetylcholine. I(ACh) was mimicked by the current induced by
      nicotine (I(Nic); EC(50)=52 microM). I(Nic) was also blocked by atropine
      (EC(50)=1.7 microM) and hexamethonium (EC(50)=3.6 microM). 5-Hydroxytryptamine (5
      HT) also inhibited I(ACh) in a concentration-dependent manner (EC(50)=180 microM)
      in the experiments carried out in the presence of a 5-HT(3) receptor antagonist.
      5-HT had a similar inhibitory effect after the desensitization of 5-HT(3)
      receptors or in neurons with relative small 5-HT(3)-mediated currents. The
      inhibitory actions of hexamethonium, atropine, and 5-HT on I(ACh) were voltage
      dependent. Thus, inhibition was significantly smaller for outward currents
      (recorded at +40 mV) than for inward currents (recorded at -60 mV). Our
      observations indicate that the I(ACh) of submucosal neurons are mediated by
      activation of nicotinic channels, which are blocked by atropine, 5-HT, and
      hexamethonium. The possibility that one of the 5-HT roles in the gastrointestinal
      tract might be to directly modulate nicotinic channels is discussed.

PMID- 11239912
TI  - Effects of simple aromatic compounds and flavonoids on Ca2+ fluxes in rat
      pituitary GH(4)C(1) cells.
AB  - The biological activity of phenolic compounds from plants is well documented in
      vitro, but little is known about the possible effect of simple aromatic compounds
      and flavonoids on voltage-operated Ca2+ channels (VOCCs). In pituitary cells,
      several intracellular pathways may regulate the activity of VOCCs. In this study,
      we investigated the effect of nine phenylpropanes and metanes, and 20 flavonoids
      on high K(+)-induced 45Ca2+ entry in clonal rat pituitary GH(4)C(1) cells. At the
      highest dose tested (20 microg/ml), flavone (a flavone) inhibited 45Ca2+ entry by
      63.5%, naringenin (a flavanone) by 56.3% and genistein (an isoflavone) by 54.6%.
      The phenylmetane derivative octyl gallate was the most potent compound tested,
      with an IC(50) value of 15.0 microg/ml. The IC(50) value for the reference
      compound verapamil hydrochloride was 3.0 microg/ml. In sharp contrast to the
      above, the flavonols quercetin and morin potentiated 45Ca2+ entry. At 20
      microg/ml, quercetin increased 45Ca2+ entry by 54.1% and morin by 48.0%.
      Quercetin increased the cellular cAMP content in a concentration-dependent
      manner. H 89, an inhibitor of protein kinase A, inhibited the effect of quercetin
      on 45Ca2+ entry. The results thus suggest that the effect of quercetin is the
      result of a protein kinase A-mediated activation of VOCCs. Quercetin induced a
      rapid and marked increase in both the transient (143.1+/-4.2%) and delayed
      (198.8+/-10.0%) Ca2+ currents, measured by the whole cell patch clamp technique.
      The onset of the inhibitory effect of octyl gallate was slow, but resulted in an
      almost complete inhibition of both Ca2+ currents.

PMID- 11239913
TI  - Inhibitory effects of SR141716A on G-protein activation in rat brain.
AB  - N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole
      3-carboxamide hydrochloride (SR141716A), a cannabinoid CB(1) receptor antagonist,
      has inverse agonist effects in cannabinoid CB(1) receptor-expressing cell lines,
      brain and peripheral organs. These studies characterized SR141716A-inhibited G
      protein activity by measuring [35S]GTPgammaS binding. Maximal inhibition of basal
      [35S]GTPgammaS binding in cerebellar membranes was 50%. The EC(50) value for
      inhibition of [35S]GTPgammaS binding was 4.4 microM, whereas the K(e) for
      inhibition of R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]
      1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate (WIN 55,212-2)-stimulated
      [35S]GTPgammaS binding was 0.6 nM. [35S]GTPgammaS autoradiography was used to
      examine the regional specificity of SR141716A inhibition. SR141716A inhibited
      basal [35S]GTPgammaS binding in all regions examined, with inhibition ranging
      from approximately 20% in caudate-putamen to 40% in hippocampus. These studies
      demonstrate that SR141716A is a competitive antagonist at nanomolar
      concentrations, whereas it inhibits basal receptor-mediated G-protein activity at
      micromolar concentrations. These data suggest that the apparent inverse agonist
      effect is either not cannabinoid CB(1) receptor-specific or that SR141716A is
      binding to different sites on the cannabinoid CB(1) receptor to produce inverse
      agonist versus competitive antagonist effects.

PMID- 11239914
TI  - Stimulation of intracellular sphingosine-1-phosphate production by G-protein
      coupled sphingosine-1-phosphate receptors.
AB  - Recently, a family of G-protein-coupled receptors named endothelial
      differentiation gene (Edg) receptor family has been identified, which are
      specifically activated by the two serum lipids, sphingosine-1-phosphate and
      lysophosphatidic acid. Sphingosine-1-phosphate can also act intracellularly to
      release Ca2+ from intracellular stores. Since in several cell types, G-protein
      coupled lysophosphatidic acid or sphingosine-1-phosphate receptors mobilize Ca2+
      in the absence of a measurable phospholipase C stimulation, it was analysed here
      whether intracellular sphingosine-1-phosphate production was the signalling
      mechanism used by extracellular sphingosine-1-phosphate for mobilization of
      stored Ca2+. Sphingosine-1-phosphate and the low affinity sphingosine-1-phosphate
      receptor agonist, sphingosylphosphorylcholine, induced a rapid, transient and
      nearly complete pertussis toxin-sensitive Ca2+ mobilization in human embryonic
      kidney (HEK-293) cells. The G-protein-coupled sphingosine-1-phosphate receptors,
      Edg-1, Edg-3 and Edg-5, were found to be endogenously expressed in these cells.
      Most interestingly, sphingosine-1-phosphate and sphingosylphosphorylcholine did
      not induce a measurable production of inositol-1,4,5-trisphosphate or
      accumulation of inositol phosphates. Instead, sphingosine-1-phosphate and
      sphingosylphosphorylcholine induced a rapid and transient increase in production
      of intracellular sphingosine-1-phosphate with a maximum of about 1.4-fold at 30
      s. Stimulation of sphingosine-1-phosphate formation by sphingosine-1-phosphate
      and sphingosylphosphorylcholine was fully blocked by pertussis toxin, indicating
      that extracellular sphingosine-1-phosphate via endogenously expressed G(i)
      coupled receptors induces a stimulation of intracellular sphingosine-1-phosphate
      production. As sphingosine-1-phosphate- and sphingosylphosphorylcholine-induced
      increases in intracellular Ca2+ were blunted by sphingosine kinase inhibitors,
      this sphingosine-1-phosphate production appears to mediate Ca2+ signalling by
      extracellular sphingosine-1-phosphate and sphingosylphosphorylcholine in HEK-293
      cells.

PMID- 11239915
TI  - Anti-mitogenic action of opioid peptides on epidermal growth factor-stimulated
      uterine cells.
AB  - Endogenous opioid peptides are negative regulators of estradiol-induced uterine
      cell proliferation. To investigate the possible molecular target site(s) of their
      anti-mitogenic action, we examined the effect of opioid peptides on epidermal
      growth factor-induced cell proliferation both in uterine primary cell cultures
      prepared from adult rats and in human myometrial smooth muscle cell lines.
      Epidermal growth factor (EGF) significantly increased cell density in both types
      of cultured monolayers. This EGF-induced stimulation of cell proliferation was
      blocked by [D-Met(2)-Pro(5)]enkephalinamide in a time-dependent, receptor
      mediated manner. The effective concentrations were within the physiological
      nanomolar range. Enkephalinamide did not have any effect on the basal rate of
      proliferation of the uterine cells. Our results on this novel physiological cross
      talk suggest that shared step(s) of the mechanism of action of estradiol and EGF
      might be targeted by opioid peptides and not the general machinery of cell
      proliferation.

PMID- 11239916
TI  - Effects of angiotensin IV and angiotensin-(1-7) on basal and angiotensin II
      stimulated cytosolic Ca2+ in mesangial cells.
AB  - This study analyzed the influence of two main metabolites of angiotensin II,
      angiotensin IV and angiotensin-(1-7), on basal and angiotensin II-dependent
      [Ca2+](i) in rat mesangial cells. Angiotensin IV behaved as a weak agonist. Its
      effects were abolished by angiotensin AT(1) receptor antagonists. Treatment with
      angiotensin II abolished the effect of a subsequent treatment with angiotensin IV
      whereas two successive angiotensin IV-dependent [Ca2+](i) peaks were obtained.
      Angiotensin II increased [Ca2+](i) in a Ca2+-free medium whereas angiotensin IV
      was inactive. Leucine-valine-valine-hemorphin 7, a hemorphin specific for the
      angiotensin AT(4) receptor, was devoid of any agonistic or antagonistic effect.
      In contrast, angiotensin-(1-7), if without influence on basal [Ca2+](i),
      inhibited angiotensin II- and angiotensin IV-dependent [Ca2+](i) increases. Total
      inhibition of the angiotensin IV effect was obtained whereas association of
      angiotensin-(1-7) to 8-(NN-diethylamino)-octyl-3,4,5-trimethoxybenzoate, an
      inhibitor of inositol phosphate-mediated Ca2+ release, was necessary to suppress
      the effect of angiotensin II. These results provide evidence that angiotensin II
      metabolites may participate in the control of [Ca2+](i) in mesangial cells at the
      initial stage of binding to the angiotensin AT(1) receptors.

PMID- 11239918
TI  - Analysis of [3H]bremazocine binding in single and combinatorial opioid receptor
      knockout mice.
AB  - Despite ample pharmacological evidence for the existence of multiple mu-, delta-
      and kappa-opioid receptor subtypes, only three genes encoding mu-(MOR), delta
      (DOR) and kappa-(KOR) opioid receptor have been cloned. The KOR gene encodes
      kappa(1)-sites, which specifically bind arylacetamide compounds, and the possible
      existence of kappa-opioid receptor subtypes derived from another kappa-opioid
      receptor gene, yet to be characterized, remains a very contentious issue.
      kappa(2)-Opioid receptors are described as binding sites typically labelled by
      the non-selective benzomorphan ligand [3H]bremazocine in the presence of mu-,
      delta- and kappa(1)-opioid receptor blocking ligands. To investigate the genetic
      origin of kappa(2)-opioid receptors, we have carried out homogenate binding
      experiments with [3H]bremazocine in brains of single MOR-, DOR-, KOR- and double
      MOR/DOR-deficient mice. Scatchard analysis showed that 68+/-12% of the binding
      sites arise from the MOR gene, 27+/-1% from the DOR gene and 14.5+/-0.2% from the
      KOR gene, indicating that the three known genes account for total [3H]bremazocine
      binding. Experiments in the presence of mu-, delta- and kappa(1)-opioid receptor
      suppressor ligands further showed that non-kappa(1)-opioid receptor labelling can
      be accounted for by binding to both the mu- and delta-opioid receptors. Finally,
      [3H]bremazocine binding experiments performed on brain membranes from the triple
      MOR/DOR/KOR-deficient mice revealed a complete absence of binding sites,
      confirming definitively that no additional gene is required to explain the total
      population of [3H]bremazocine binding sites. Altogether the data show that the
      putative kappa(2)-opioid receptors are in fact a mixed population of KOR, DOR and
      predominantly MOR gene products.

PMID- 11239917
TI  - Oxidative stress and c-Jun-amino-terminal kinase activation involved in apoptosis
      of primary astrocytes induced by disulfiram-Cu(2+) complex.
AB  - Disulfiram is frequently used in the treatment of alcoholism. In this study, we
      found that CuCl(2) (1-10 microM), but not other metal ions (Fe(2+), Zn(2+),
      Pb(2+)), markedly potentiated disulfiram-induced cytotoxicity by 440-fold in
      primary astrocytes. Thus, the molecular mechanisms of the cytotoxic effects
      induced by the disulfiram-Cu(2+) complex were explored. The changes in morphology
      (nuclear condensation and apoptotic body formation) and hypodiploidy of DNA
      suggested that the disulfiram-Cu(2+) complex induced an apoptotic process. Our
      studies of the death-signaling pathway reveal that decreased mitochondrial
      membrane potential, increased free radical production, and depletion of non
      protein-thiols (glutathione) were involved. The disulfiram-Cu(2+) complex
      activated c-Jun-amino-terminal kinase (JNK) and caspase-3 followed by poly (ADP
      ribose) polymerase degradation in a time-dependent manner. Moreover, the cellular
      Cu content was markedly increased and the copper chelator bathocuproine
      disulfonate abolished all of these cellular events, suggesting that Cu(2+) is
      essential for death signaling. The antioxidants N-acetylcysteine and vitamin C
      also inhibited the cytotoxic effect. Thus, we conclude that the disulfiram-Cu(2+)
      complex induces apoptosis and perhaps necrosis at a late stage mediated by
      oxidative stress followed by sequential activation of JNK, caspase-3 and poly
      (ADP-ribose) polymerase degradation. These findings imply that the axonal
      degeneration and neurotoxicity observed after the chronic administration of
      disulfiram are perhaps, at least in part, due to the cytotoxic effect of the
      disulfiram-Cu(2+) complex formed endogenously.

PMID- 11239919
TI  - Inhibition by L-3,4-dihydroxyphenylalanine of hippocampal CA1 neurons with
      facilitation of noradrenaline and gamma-aminobutyric acid release.
AB  - Electrophysiological studies were performed to elucidate whether L-3,4
      dihydroxyphenylalanine (L-DOPA) acted on hippocampal CA1 neurons, since this drug
      has been reported to act as a neurotransmitter in the hypothalamus and striatum.
      Hippocampal slices (450 microM thick) obtained from male Wistar rats (4-7 weeks
      of age) were placed in a bath (maintained at 30+/-1 degrees C) continuously
      perfused with artificial cerebrospinal fluid. The population spikes elicited by
      electrical stimuli applied to the Schaffer collateral/commissural fibers were
      recorded in the hippocampal CA1 region, using a glass micropipette filled with 3
      M NaCl. Drugs were applied in the bath through a perfusion system. The population
      spikes were inhibited by L-DOPA (1 nM-10 microM) with a bell-shaped concentration
      response curve (n=7-15). Maximum inhibitory effects were obtained at 100 nM. L
      DOPA cyclohexyl ester, a putative L-DOPA recognition site antagonist, antagonized
      the L-DOPA-induced inhibition of population spike. However, the inhibition
      remained unaffected in the presence of 3-hydroxybenzylhydrazine, an aromatic
      amino acid decarboxylase inhibitor. Furthermore, bath application of either
      phentolamine, an alpha-adrenoceptor antagonist, or bicuculline, a GABA(A)
      receptor antagonist, antagonized the inhibitory effects of L-DOPA on population
      spikes. In addition, bicuculline (1 microM) antagonized the inhibition of
      population spike induced by 6-fluoronorepinephrine (10 microM), an alpha
      adrenoceptor agonist, while phentolamine (10 microM) did not affect the muscimol
      (1 microM)-induced inhibition. These results suggested that L-DOPA itself acted
      on L-DOPA recognition sites to release noradrenaline, and that the latter
      facilitates gamma-aminobutyric acid (GABA) release via alpha-adrenoceptors
      located on the GABA-containing cells and/or their nerve terminals, thereby
      inhibiting the population spikes in the hippocampal CA1 field.

PMID- 11239921
TI  - Perinatal opioids reduce striatal nerve growth factor content in rat striatum.
AB  - Both human and animal models indicate that perinatal methadone exposure produces
      a variety of short- and long-term neurobehavioral consequences, including
      disruption of normal development of striatal cholinergic neurons. Despite this,
      methadone maintenance is a standard method of managing pregnant heroin addicts,
      and the opioid receptor partial agonist buprenorphine is under evaluation for the
      same use. We now report that perinatal administration of either methadone or
      buprenorphine reduces the content of the neurotrophic factor nerve growth factor
      (NGF) in rat striatum, which may explain the behavioral deficits observed.
      Furthermore, although NGF content is reduced, there are no corresponding
      reductions in striatal NGF mRNA.

PMID- 11239920
TI  - GABAergic blockade of cocaine-associated cue-induced increases in nucleus
      accumbens dopamine.
AB  - Environments previously associated with drug use can become one of the most
      common factors triggering relapse to drug-seeking behavior. To better understand
      the neurochemical mechanisms potentially mediating these cues, we measured
      nucleus accumbens dopamine levels in animals exposed to environmental cues
      previously paired with cocaine administration. In animals exposed to a cocaine
      paired environment nucleus accumbens dopamine increased by 25%. When administered
      2.5 h prior to presentation of the environmental trigger, racemic vigabatrin (an
      irreversible inhibitor of gamma-aminobutyric acid (GABA)-transaminase) abolished
      this cue-induced increase. Conversely, R-(-)-vigabatrin, the inactive enantiomer,
      had no effect. Combined with our earlier findings, these studies support the
      potential therapeutic benefit of this enzyme-based GABAergic strategy to modulate
      brain dopamine and the subsequent treatment of drug addiction.

PMID- 11239922
TI  - Neuropeptide Y Y(5) receptor antagonist CGP71683A: the effects on food intake and
      anxiety-related behavior in the rat.
AB  - The effects of neuropeptide Y Y(5) receptor antagonist (trans-naphtalene-1
      sulphonic acid [4-[(4-amino-quinazolin-2-ylamino)-methyl]-cyclohexylmethyl]-amide
      hydrochloride; CGP71683A), on food intake, anxiety and locomotor activity were
      studied. CGP71683A (1-10 mg/kg, i.p.) dose-dependently decreased nocturnal and
      fasting-induced food intake. CGP71683A did not have an anxiogenic-like effect in
      the rat social interaction test. In the elevated plus-maze test, where novel
      neuropeptide Y Y(1) receptor antagonist (2R)-5-([amino(imino)methyl)amino)-2
      [(2.2-diphenylacetyl)-amino]-N-[(1R)-1-(4-hydroxyphenyl)ethyl-pentanamide (H
      409/22) had anxiogenic-like effect, CGP71683A was inactive. In the open-field
      test, carried out immediately after the elevated plus-maze test, CGP71683A
      inhibited horizontal and vertical activity. CGP71683A did modify the habituation
      of locomotor response in novel environment. These data show that the inhibition
      of food intake induced by CGP71683A could not be explained by increased
      fearfulness, a state that is induced by neuropeptide Y Y(1) receptor antagonists.
      Thus, our data, obtained with first neuropeptide Y Y(5) receptor antagonist
      CGP71683A, suggest that in contrast to the neuropeptide Y Y(1) receptor, Y(5)
      receptor is not involved in tonic neuropeptide Y-induced anxiolysis.

PMID- 11239923
TI  - The octadecaneuropeptide [diazepam-binding inhibitor (33-50)] exerts potent
      anorexigenic effects in rodents.
AB  - The effects of intracerebroventricular administration of the octadecaneuropeptide
      ODN on food intake have been investigated in rat and mouse. In rats deprived of
      food from 9:00 a.m. to 7:00 p.m., i.c.v. injection of ODN (30 to 100 ng) provoked
      a dose-dependent reduction of food consumption during the following 12-h
      nocturnal period. At a dose of 100 ng, ODN almost completely suppressed food
      intake. Treatment of rats with diazepam (2 mg/kg s.c.; 15 min before ODN
      administration) did not affect the anorexigenic response evoked by 100 ng ODN.
      Continuous i.c.v. infusion of ODN (10 ng/h during 15 days) using osmotic
      minipumps, significantly reduced food intake during the 2nd, 3rd and 4th days of
      treatment. The decrease in food consumption was associated with a significant
      reduction in body weight, which persisted during the 15-day duration of the
      experiment. In mice deprived of food for 18 h, i.c.v. administration of a low
      dose of ODN (5 ng) significantly reduced food intake. Treatment of mice with
      diazepam (1 mg/kg s.c.; 10 min before ODN administration) did not prevent the
      inhibitory effect of ODN (100 ng) on food intake. The C-terminal octapeptide
      fragment of ODN mimicked the anorexigenic effect of the intact peptide. Taken
      together, the present data demonstrate that i.c.v. injection of ODN causes, in
      both rat and mouse, a long-lasting anorexigenic effect that is not mediated
      through central-type benzodiazepine receptors. The biologically active region of
      ODN appears to be located in the C-terminal domain of the peptide.

PMID- 11239924
TI  - Population pharmacokinetic-pharmacodynamic modelling of S 15535, a 5-HT(1A)
      receptor agonist, using a behavioural model in rats.
AB  - The pharmacokinetic-pharmacodynamic relationship of S 15535 (1-(benzodioxan-5-yl)
      4-(indan-2-yl)piperazine) and its active 5-hydroxy metabolite S 32784 (1
      (benzodioxan-5-yl) 4-(5-hydroxyindan-2-yl)piperazine), and buspirone as a
      reference, were studied in male Wistar rats using a behavioural model of anxiety
      by determining the reduction in the number of fear-induced ultrasonic
      vocalisations. S 15535 and buspirone were administered p.o. and i.v. S 32784,
      present in man but not in rat, was administered i.v. The pharmacokinetics and
      pharmacokinetic-pharmacodynamic relationships were described using non-linear
      mixed effects modelling. The no-drug effect was constant and all compounds were
      active in the model, reducing ultrasonic vocalisations immediately after
      administration. The sigmoid E(max) model was used to describe the pharmacokinetic
      pharmacodynamic relationships, with E(max) values of a 90% decrease in baseline
      ultrasonic vocalisations. Corrected for plasma protein binding, all compounds
      showed similar potency. The study shows that ultrasonic vocalisations can be
      considered a suitable endpoint for the anxiolytic effect when used in conjunction
      with non-linear mixed effects modelling to overcome the limited sampling and
      effect measurements.

PMID- 11239925
TI  - Systemic EMD 68843 injections reduce anxiety in the shock-probe, but not the plus
      maze test.
AB  - Selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors and 5-HT(1A)
      receptor agonists are believed to reduce anxiety. In the present study we
      examined the effects of injections of 5-(4-[4-(5-cyano-3-indolyl)-butyl]-1
      piperazinyl)-benzofuran-2-carboxamide hydrochloride salt (EMD 68843), a 5-HT(1A)
      receptor agonist and selective 5-HT reuptake inhibitor, in two animal models of
      anxiety, plus-maze and shock-probe. Rats received intraperitoneal injections of
      vehicle, diazepam (2.5 mg/kg), or EMD 68843 (10, 20, or 40 mg/kg) 1 h prior to
      testing. Diazepam at the single dose tested and EMD 68843 dose-dependently
      (significantly at 20 and 40 mg/kg) reduced burying in shock-probe. However, only
      diazepam significantly increased open arm exploration in the plus-maze.
      Therefore, EMD 68843 has task specific anxiolytic properties.

PMID- 11239926
TI  - Characterization of CGRP(1) receptors in the guinea pig basilar artery.
AB  - The purpose of the present study was to characterise receptors mediating
      calcitonin gene-related peptide (CGRP)-induced relaxation of guinea pig basilar
      artery. This was done by investigating vasomotor responses in vitro and
      performing autoradiographic binding studies. We also intended to study the
      importance of an intact endothelium. Agonist studies showed that peptides of the
      CGRP family induced relaxation of the guinea pig basilar artery with the
      following order of potency: human beta-CGRP=human alpha
      CGRP>>adrenomedullin=[acetamidomethyl-Cys(2,7)]alpha-human CGRP
      ([Cys(ACM)(2,7)]CGRP)=amylin. These data are in concord with those of the
      autoradiographic binding studies that showed displacement of [125I] human alpha
      CGRP binding with the following order of potency: human alpha-CGRP=human beta
      CGRP>>adrenomedullin=human alpha-CGRP-(8-37)>>Cys(ACM)(2,7)]CGRP. In blockade
      experiments, the relaxant responses to human alpha- and human beta-CGRP were
      competitively blocked by the CGRP(1) receptor antagonist human alpha-CGRP-(8-37),
      while those of adrenomedullin and amylin were blocked non-competitively. In order
      to examine whether amylin induced relaxation via amylin or CGRP receptors, we
      studied the antagonistic effect of amylin-(8-37) on the weak relaxant response to
      amylin and found that it was not blocked by amylin-(8-37). These findings,
      together with the finding that the CGRP(2) receptor agonist [Cys(ACM)(2,7)]CGRP
      only induced a weak relaxation in the highest concentrations examined, suggest
      that the CGRP family of peptides mediate relaxation by CGRP(1)-type receptors.
      Removal of the endothelium, the addition of N(G)-nitro-L-arginine methyl ester (L
      NAME), methylene blue or indomethacin did not affect the concentration-response
      curves of the CGRP analogues, neither in the presence nor in the absence of human
      CGRP-(8-37). The study shows the presence of a relaxant CGRP(1) receptor on the
      smooth muscle cells of guinea pig basilar artery. Various endothelial factors did
      not influence relaxant responses.

PMID- 11239927
TI  - Cardiovascular effects of SL65.0472, a 5-HT receptor antagonist.
AB  - In this study, we describe the cardiovascular effects of SL65.0472 (7-fluoro-2
      oxo-4-[2-[4-(thieno[3,2-c] pyridin-4-yl) piperazin-l-yl] ethyl]-1, 2
      dihydroquinoline-1-acetamide), a novel 5-hydroxytryptamine (5-HT) receptor
      antagonist developed for the treatment of cardiovascular disease, in several in
      vivo models. The haemodynamic profile of SL65.0472 was evaluated in anaesthetised
      dogs. Following i.v. bolus doses of 0.03 mg/kg i.v. and 0.3 mg/kg, no significant
      changes in cardiac output, contractility or rate, systemic and pulmonary
      pressures, regional blood flows and vascular resistances or electrocardiogram
      were noted. After 1 mg/kg i.v. SL65.0472 significantly reduced arterial blood
      pressure. In conscious spontaneously hypertensive rats administration of
      SL65.0472 0.5 mg/kg p.o. had no effect on mean arterial blood pressure or heart
      rate. Vasoconstriction produced by 5-HT results primarily from the stimulation of
      two receptor subtypes, 5-HT(1B) and 5-HT(2A) receptors. In anaesthetised dogs
      SL65.0472 antagonised sumatriptan-induced decreases in saphenous vein diameter (5
      HT(1B)-receptor mediated) with an ID(50) of 10.1 microg/kg i.v. (95% c.l. 8.3
      12.4). In anaesthetised pithed rats SL65.0472 inhibited 5-HT pressor responses
      (5HT(2A)-receptor mediated) with ID(50) values of 1.38 microg/kg i.v. (95% c.l.
      1.15-1.64) and 31.1 microg/kg p.o. (95% c.l. 22.6-42.6). The duration of the 5
      HT(2A)-receptor antagonist effect of SL65.0472 following oral administration was
      evaluated in conscious rats. SL65.0472 (0.1 mg/kg p.o.) markedly inhibited 5-HT
      pressor responses 1 and 6 h after administration. Therefore, in vivo, SL65.0472
      potently antagonises vasoconstriction mediated by 5-HT(1B) and 5-HT(2A) receptors
      but has minimal direct haemodynamic effects.

PMID- 11239928
TI  - Preventive effect of ebselen on acute gastric mucosal lesion development in rats
      treated with compound 48/80.
AB  - The preventive effect of ebselen, a seleno-organic compound, which is known to
      possess glutathione peroxidase-like activity and antioxidative and anti
      inflammatory properties, on the development of acute gastric mucosal lesions was
      examined in rats with a single injection of compound 48/80 (0.75 mg/kg, i.p.), a
      mast cell degranulator. Pre-administration of ebselen (p.o.) at a dose of 50 or
      100 mg/kg, but not 10 mg/kg, prevented gastric mucosal lesion development at 3 h,
      but not gastric mucosal lesion formation at 0.5 h, after compound 48/80
      injection, although any dose of pre-administered ebselen did not affect decreased
      gastric mucosal blood flow and increased serum serotonin and histamine
      concentrations found at 0.5 and 3 h after compound 48/80 injection. A decrease in
      Se-glutathione peroxidase activity and increases in the activities of
      myeloperoxidase, an index of tissue neutrophil infiltration, and xanthine oxidase
      and the concentration of thiobarbituric acid reactive substances, an index of
      lipid peroxidation, were found in gastric mucosal tissues at 0.5 h after compound
      48/80 injection and these changes were further enhanced at 3 h. Pre
      administration of ebselen (p.o.) at a dose of 50 or 100 mg/kg, but not 10 mg/kg,
      attenuated all these changes found at 3 h after compound 48/80 injection. These
      preventive effects of ebselen occurred in a dose-dependent manner. The present
      results indicate that pre-administered ebselen prevents the development of
      compound 48/80-induced acute gastric mucosal lesions in rats, and suggest that
      this preventive effect of ebselen could be due to its glutathione peroxidase-like
      activity and antioxidative and anti-inflammatory properties.

PMID- 11239929
TI  - The timing of endothelin and nitric oxide inhibition affects survival in a mice
      model of septic shock.
AB  - The effect of endothelin and nitric oxide (NO) inhibition on survival from septic
      shock was investigated in male Swiss albino mice (20-40 g), with particular
      emphasis on the timing of the administration of their blockers after Escherichia
      coli endotoxin (lipopolysaccharide, O55:B5, 60 mg kg(-1), i.p.) challenge. Mice
      were injected with the endothelin receptor antagonist bosentan (30 mg kg(-1),
      i.p., either 2 or 12 h after endotoxin) alone or in addition to the NO synthase
      blockers L-canavanine (100 mg kg(-1), i.p.), N(G)-nitro-L-arginine methyl ester
      (L-NAME, 3 mg kg(-1), i.p.) or aminoguanidine (15 mg kg(-1), i.p.), which were
      also given twice at 2 and 6 h after endotoxin. Control animals received saline,
      and survival rates in each group (n=10) were recorded over 24 h at 6-h intervals.
      At 24 h, the survival rate was 10% in controls, but 30% (n.s.) and 70% (P<0.05)
      in animals that received only bosentan at 2 and 12 h, respectively, indicating a
      relatively late involvement of endothelin in comparison to NO. In contrast, these
      figures were 70% (P<0.05) and 80% (P<0.05) at 12 h for L-NAME and L-canavanine,
      respectively, and 10% (n.s.) at 24 h, implying a relatively early involvement of
      NO compared to endothelin. Interestingly, survival in the aminoguanidine group
      (75% at 24 h, P<0.05 vs. controls) was markedly higher than that in the L-NAME
      and L-canavanine groups, an effect that was attributed to mechanisms other than
      NO inhibition. Survival was better (60%, P<0.05 vs. endotoxin alone) when
      bosentan was given at 2 h in combination with L-NAME, but the best outcome (90%
      survival, P<0.05) was observed in animals when bosentan was given at 12 h and L
      NAME was injected twice at 2 and 6 h. However, the statistical analysis revealed
      no significant additional beneficial effect of L-NAME coadministered with
      bosentan. Therefore, we conclude that NO is involved during the earlier phases of
      septic shock in comparison to a relatively late involvement of endothelin
      peptides, and that bosentan alone appears to be beneficial when administered at
      least 12 h after the endotoxin challenge in our mice model of septic shock.

PMID- 11239930
TI  - Opioid receptors on bone marrow neutrophils modulate chemotaxis and CD11b/CD18
      expression.
AB  - Opiates impair neutrophil-mediated host defense, but the involvement of kappa
      opioid receptors in this action has not been defined. The selective kappa-opioid
      receptor agonist [trans-(+)3,4-dichloro-N-methyl-N[2-(1-pyrrolidinyl)
      cyclohexyl]benzeneacetamide methanesulfonate inhibited macrophage inflammatory
      protein-2-induced chemotaxis of bone marrow neutrophils from C57BL/6 mice. Its
      effects were concentration-dependent (pIC(50)=10.40+/-0.61) and inhibited by
      naloxone (K(e)=0.27 nM). The kappa-opioid receptor agonists bremazocine and ICI
      204, 488 also inhibited chemotaxis, as did the respective mu- and delta-opioid
      receptor agonists [D-Ala(2), N-methyl-Phe(4), Gly(5)-ol]enkephalin and [D
      Pen(2,5)]enkephalin albeit with lower potencies. U-50,488H also decreased
      neutrophil expression of the beta(2) integrin CD11b/CD18 (Mac-1) and adhesion to
      plastic in a naloxone-reversible manner. The results indicate that kappa-opioid
      receptors expressed by neutrophils rapidly modulate chemotaxis and adhesion in
      vitro.

PMID- 11239931
TI  - Immunologically induced histamine release from rat peritoneal mast cells is
      enhanced by low levels of substance P.
AB  - Although direct activation of mast cells by high concentrations (>10(-6) M) of
      substance P is well established, the effect of sub-micromolar concentrations of
      the neuropeptide on mast cell activation has not been reported. We hence
      investigated if substance P would modulate immunologic activation of mast cells
      by studying the effect of the neuropeptide on anti-rat immunologlobulin E
      antibody (anti-IgE)-induced histamine release from purified rat peritoneal mast
      cells. We observed that substance P could dose-dependently potentiate anti-IgE
      induced histamine release from rat peritoneal mast cells at concentrations (3x10(
      9) M to 3x10(-7) M) which alone induced insignificant or low level of histamine
      release. While the potentiating effect of substance P was not suppressed by any
      of the non-peptide tachykinin receptor antagonists CP99994 ((2S,3S)-3-(2
      methoxybenzylamino)-2-phenylpiperidine), SR48968 ((S)-N-methyl-N-(4-acetylamino-4
      phenylpiperidino)-2-(3,4-dichlorophenyl) butyl-benzamide) and SR142801 ((S)-(N)
      (1-[3-(1-benzoyl-3(3,4-dichlorophenyl)piperidine-3-yl)propyl]-4-phenylpiperidin-4
      yl)-N-methyl-acetamide), it was mimicked by compound 48/80 and suppressed by
      benzalkonium chloride. Hence, substance P enhanced anti-IgE-induced histamine
      release through a similar receptor-independent mechanism as the direct mast cell
      activating action of polybasic compounds. Since high concentrations of substance
      P required for directly activating mast cells may not be achievable
      physiologically, the enhancing actions of the neuropeptide on the immunologic
      activation of mast cells may be more clinically relevant in the pathogenesis of
      various inflammatory conditions.

PMID- 11239933
TI  - Recent trends in research on congenital toxoplasmosis.

PMID- 11239932
TI  - Triclosan inhibits the growth of Plasmodium falciparum and Toxoplasma gondii by
      inhibition of apicomplexan Fab I.
AB  - Fab I, enoyl acyl carrier protein reductase (ENR), is an enzyme used in fatty
      acid synthesis. It is a single chain polypeptide in plants, bacteria, and
      mycobacteria, but is part of a complex polypeptide in animals and fungi. Certain
      other enzymes in fatty acid synthesis in apicomplexan parasites appear to have
      multiple forms, homologous to either a plastid, plant-like single chain enzyme or
      more like the animal complex polypeptide chain. We identified a plant-like Fab I
      in Plasmodium falciparum and modelled the structure on the Brassica napus and
      Escherichia coli structures, alone and complexed to triclosan (5-chloro-2-[2,4
      dichlorophenoxy] phenol]), which confirmed all the requisite features of an ENR
      and its interactions with triclosan. Like the remarkable effect of triclosan on a
      wide variety of bacteria, this compound markedly inhibits growth and survival of
      the apicomplexan parasites P. falciparum and Toxoplasma gondii at low (i.e. IC50
      congruent with150-2000 and 62 ng/ml, respectively) concentrations. Discovery and
      characterisation of an apicomplexan Fab I and discovery of triclosan as lead
      compound provide means to rationally design novel inhibitory compounds.

PMID- 11239934
TI  - Differential adhesion of major surface proteins 1a and 1b of the ehrlichial
      cattle pathogen Anaplasma marginale to bovine erythrocytes and tick cells.
AB  - Anaplasma marginale is a tick-borne ehrlichial pathogen of cattle for which six
      major surface proteins (MSPs) have been described. The MSP1 complex, a
      heterodimer composed of MSP1a and MSP1b, was shown to induce a protective immune
      response in cattle and both proteins have been identified as putative adhesins
      for bovine erythrocytes. In this study the role of MSP1a and MSP1b as adhesins
      for bovine erythrocytes and tick cells was defined. msp1alpha and msp1beta1 genes
      from the Oklahoma isolate of A. marginale were cloned and expressed in
      Escherichia coli K-12 under the control of endogenous and tac promoters for both
      low and high level protein expression. Expression of the recombinant polypeptides
      was confirmed and localised on the surface of transformed E. coli. The adhesion
      properties of MSP1a and MSP1b were determined by allowing recombinant E. coli
      expressing these surface polypetides to react with bovine erythrocytes,
      Dermacentor variabilis gut cells and cultured tick cells derived from embryonic
      Ixodes scapularis. Adhesion of the recombinant E. coli to the three cell types
      was determined using recovery adhesion and microtiter haemagglutination assays,
      and by light and electron microscopy. MSP1a was shown by all methods tested to be
      an adhesin for bovine erythrocytes and both native and cultured tick cells. In
      contrast, recombinant E. coli expressing MSP1b adhered only to bovine
      erythrocytes and not to tick cells. When low expression vectors were used, single
      E. coli expressing MSP1a was seen adhered to individual tick cells while reaction
      of tick cells with the E. coli/MSP1a/high expression vector resulted in adhesion
      of multiple bacteria per cell. With electron microscopy, fusion of E. coli cell
      membranes expressing MSP1a or MSP1b with erythrocyte membranes was observed, as
      well as fusion of tick cell membranes with E. coli membranes expressing MSP1a.
      These studies demonstrated differential adhesion for MSP1a and MSP1b for which
      MSP1a is an A. marginale adhesin for both bovine erythrocytes and tick cells
      while MSP1b is an adhesin only for bovine erythrocytes. The role of the MSP1
      complex, therefore, appears to vary among vertebrate and invertebrate hosts.

PMID- 11239935
TI  - MGE-PCR: a novel approach to the analysis of Toxoplasma gondii strain
      differentiation using mobile genetic elements.
AB  - The position of mobile genetic elements (MGE) within eukaryotic genomes is often
      highly variable and we have exploited this phenomenon to develop a novel approach
      to strain differentiation in Toxoplasma gondii. Two PCR based strategies were
      designed in which specific primers were used to amplify T. gondii MGE's revealing
      information on element size and positional variation. The first PCR strategy
      involved the use of a standard two primer PCR while the second strategy used a
      single specific primer in a step-up PCR protocol. This approach was applied to T.
      gondii reference strains which were either acute virulent or avirulent to mice.
      The use of a standard two primer PCR reaction revealed the presence of a
      virulence related marker in which all avirulent strains possessed an additional
      688 bp band. The single primer PCR strategy demonstrated that all virulent
      strains had identical banding patterns suggesting invariance within this group of
      strains. However, all avirulent strains had different banding patterns indicating
      the presence of a number of individual lineages within this group. The
      applicability and sensitivity of MGE-PCR in epidemiological studies was
      demonstrated by direct amplification of T. gondii from sheep tissue samples. All
      sheep isolates, tested in this way, gave identical banding patterns suggesting
      the presence of an endemic Toxoplasma strain on this farm.

PMID- 11239936
TI  - Immunological inter-strain crossreactivity correlated to 18S rDNA sequence types
      in Acanthamoeba spp.
AB  - Various species of the genus Acanthamoeba have been described as potential
      pathogens; however, differentiation of acanthamoebae remains problematic. The
      genus has been divided into 12 18S rDNA sequence types, most keratitis causing
      strains exhibiting sequence type T4. We recently isolated a keratitis causing
      Acanthamoeba strain showing sequence type T6, but being morphologically identical
      to a T4 strain. The aim of our study was to find out, whether the 18S rDNA
      sequence based identification correlates to immunological differentiation. The
      protein and antigen profiles of the T6 isolate and three reference Acanthamoeba
      strains were investigated using two sera from Acanthamoeba keratitis patients and
      one serum from an asymptomatic individual. It was shown, that the T6 strain
      produces a distinctly different immunological pattern, while patterns within T4
      were identical. Affinity purified antibodies were used to further explore
      immunological cross-reactivity between sequence types. Altogether, the results of
      our study support the Acanthamoeba 18S rDNA sequence type classification in the
      investigated strains.

PMID- 11239938
TI  - Identification of antigenic differences that discriminate between cattle
      vaccinated with Anaplasma centrale and cattle naturally infected with Anaplasma
      marginale.
AB  - Monoclonal antibodies were raised against the vaccine strain of Anaplasma
      centrale used in Australia. A monoclonal antibody that reacted with an 80 kDa
      antigen was used to develop an A. centrale-specific fluorescent antibody test
      that will be useful for confirming species identity in patent infections. Another
      monoclonal antibody that reacted with a 116 kDa antigen was used to develop an A.
      centrale-specific competitive inhibition enzyme-linked immunosorbent assay
      (ELISA) for the serological identification of vaccinated cattle. The sensitivity
      of the ELISA was 100% in cattle experimentally infected with A. centrale, 97.1%
      in a vaccinated beef herd and 98.3% in a vaccinated dairy herd. The specificity
      of the ELISA was 98.6% in non-vaccinated cattle outside the Anaplasma marginale
      endemic area, 97.9% in non-vaccinated cattle within the A. marginale-endemic area
      and 100% in cattle experimentally infected with A. marginale. The ELISA detected
      antibodies to A. centrale in cattle up to 9 years after vaccination with no
      apparent decrease in sensitivity. The assay has proved extremely valuable in
      Australia for investigating reported failures of multivalent live vaccines used
      to protect cattle against anaplasmosis and babesiosis, and should be similarly
      useful elsewhere in the world where these types of vaccines are used, e.g. Israel
      and South America.

PMID- 11239937
TI  - Characterisation of nuclear ribosomal DNA sequences from Onchocerca volvulus and
      Mansonella ozzardi (Nematoda: Filarioidea) and development of a PCR-based method
      for their detection in skin biopsies.
AB  - The internal transcribed spacer region (ITS1, 5.8S gene and ITS2) of the two
      filarial nematodes Onchocerca volvulus and Mansonella ozzardi was sequenced, and
      two species-specific primers designed in the ITS2 to develop a PCR-based method
      for their specific detection and differentiation. When used with a universal
      reverse primer, the two species-specific primers gave amplification products of
      different size, which were readily separated in an agarose gel. The PCR was
      tested on skin biopsies from 51 people from three localities in Brazil where M.
      ozzardi is present, and results have been compared with those of parasitological
      examination of blood. The species-specific PCR gave a higher percentage of
      detection of infection by M. ozzardi than the parasitological examination of
      blood. No infection with O. volvulus was detected by PCR. This PCR-based assay
      may assist in determining the nature of infection in areas where both filarial
      species exist in sympatry.

PMID- 11239939
TI  - Cytokine and lymphocyte profiles in miniature swine after oral infection with
      Toxoplasma gondii oocysts.
AB  - Pigs are considered an important source of Toxoplasma gondii infection for
      humans. A major strategy for immune prophylaxis of toxoplasmosis in swine is the
      understanding of the immune response against T. gondii infection. The phenotype
      of peripheral blood mononuclear cells (PBMC) and the kinetics of interferon-gamma
      (IFN-gamma), interleukin-12 (IL-12) and interleukin-10 (IL-10) transcriptional
      changes were characterised in miniature swine following infection. A total of 66,
      4-9-month-old miniature swine were used for three experiments performed over a
      period of 2 years. All pigs were fed iota1000 oocysts of the VEG strain of T.
      gondii and blood samples were obtained on the day of inoculation and at days 3,
      6, 10, 17, 25, 32 and 40 after infection. An increase in expression of activation
      markers CD25 and SLA-DQ was detected in the first week of infection. A
      significant increase in the percentage of CD8+cells was observed in the second
      week of infection. Relative competitive RT-PCR analysis indicated an increase in
      IFN-gamma mRNA as well as a reduction in IL-10 mRNA during the second week post
      infection. Increase in IL-12 transcription was not observed until the fourth week
      of infection. The ability of the pigs to respond to T. gondii infection by
      simultaneously inducing pro-inflammatory cytokines early and anti-inflammatory
      cytokines later is a likely indication of the requirement to strike a balance
      between controlling parasite growth and avoiding cytokine toxicity.

PMID- 11239940
TI  - Evaluation of the specificity of five oligoprobes for identification of
      cyathostomin species from horses.
AB  - Here, we report evaluation of five oligoprobes designed from intergenic spacer
      (IGS) region sequences for identification of cyathostomin species. Oligoprobes
      were designed for identification of Cylicocyclus ashworthi, Cylicocyclus
      nassatus, Cylicostephanus longibursatus, Cylicostephanus goldi and a fifth probe
      designed to identify all members of this tribe. PCR amplification of IGS DNA from
      16 cyathostomin species allowed sequence comparison and identification of four
      putative species-specific probes. Southern blotting of amplified products from 16
      species showed that all probes were species-specific. The fifth probe recognised
      all 16 cyathostomin species but did not bind to members of the genus Strongylus.
      Furthermore, these probes were used to identify individual infective L3, eggs and
      L4 indicating that they will be invaluable to furthering the study of the
      epidemiology and pathogenesis of these important equine nematodes.

PMID- 11239941
TI  - The phylogenetic position of Furnestinia echeneis (Monogenea, Diplectanidae)
      based on molecular data: a case of morphological adaptation?
AB  - The genus Furnestinia (Diplectanidae) contains only one species, Furnestinia
      echeneis. However, its close morphological similarity with the genus
      Lamellodiscus (Diplectanidae) raises doubt concerning its placement in a separate
      genus. These two genera differ only by their number of lamellodiscs: one for
      Furnestinia, two for Lamellodiscus. Here, the taxonomic position of F. echeneis
      is investigated via a phylogenetic reconstruction based on partial 18S rDNA for
      F. echeneis and several Lamellodiscus species. Furnestinia echeneis appears to be
      clearly nested into the Lamellodiscus genus, these two genera should then be
      synonymised. The hypertrophy of its unique lamellodisc is hypothesised to be a
      morphological adaptation for attachment to the host.

PMID- 11239942
TI  - Evidence of post-natal transmission of Neospora caninum in Dutch dairy herds.
AB  - Eighteen dairy herds with neosporosis-associated abortions were analysed for
      antibodies against Neospora caninum. Blood samples of all cows, heifers and
      calves were collected on the same day for each farm. A total of 2430 heads of
      cattle were examined. For each herd, the seropositive and seronegative animals
      were plotted against month of birth. Analysis of seroprevalence in relation to
      age showed an equal distribution of seropositives in all age-groups in 10 herds.
      In contrast, in eight herds an age-group could be identified which had a
      significantly higher seroprevalence than the other animals in the herd. Most
      seropositive animals in the high seroprevalence age-groups had either
      seronegative dams or seronegative offspring, whereas there was a strong
      relationship between the serostatus of dams and offspring in the other animals in
      the herd. Aborting animals were mainly part of the high seroprevalence age-group.
      These findings strongly indicate a post-natal infection of the animals in the
      high seroprevalence age-groups, probably due to a point source exposure to N.
      caninum.

PMID- 11239944
TI  - Cerebrospinal fluid analysis: disease-related data patterns and evaluation
      programs.
AB  - Cerebrospinal fluid (CSF) analysis is a basic tool for diagnosis of neurological
      diseases. Knowledge regarding blood-CSF barrier function (molecular flux/CSF flow
      theory) and neuroimmunology is reviewed to aid understanding and evaluation of
      CSF data. Disease-related immunoglobulin patterns (IgG, IgA, IgM with reference
      to albumin) are described in CSF/serum quotient diagrams with the hyperbolic
      reference range for blood-derived protein fractions in CSF. Clinical relevance of
      complementary analyses (cytology, PCR, oligoclonal IgG, antibody detection and
      brain-derived proteins) is briefly discussed. Integrated CSF data reports are
      shown with numerical and graphical data representation, reference range-related
      interpretation and diagnosis-related comments. The principles and rationale of
      general CSF analysis reported in this review should enable the reader to
      accurately interpret CSF data profiles, and to plan a proper evaluation of new
      brain- or blood-derived analytes in CSF.

PMID- 11239946
TI  - Antibody types and IgG subclasses in paraneoplastic neurological syndromes.
AB  - Three major patterns of antineuronal antibody response have been identified in
      patients with paraneoplastic neurological syndromes: Type I ('Anti-Yo'),
      associated with cerebellar degeneration in the setting of breast or gynecological
      cancer, Type IIa ('anti-Hu') associated with encephalomyeloneuritis in patients
      with small cell carcinoma of the lung, and Type IIb ('anti-Ri') associated with
      breast cancer. We have employed immunofluorescence methods to determine the
      antibody classes and the IgG subclasses which react with neurons in each of these
      patterns of paraneoplastic antibody response. In this study, IgG was the only
      antibody class identified; IgM and IgA antibodies were not found. IgG1 was the
      major subclass represented and was found in 9/9 patients with Type I antibody
      response, 26/27 patients with Type IIa antibody response, and 3/3 patients with
      Type IIb antibody response. Many patients also exhibited positive staining for
      IgG2 and IgG3. Trace amounts of IgG4 antineuronal antibodies were detected in a
      single patient with Type I antibody response; IgG4 antibodies were not found in
      other patients. Patients with paraneoplastic neurological syndromes exhibit an
      antibody response which is overwhelmingly IgG and is comprised predominantly of
      IgG subclasses capable of fixing complement. The role of these antibodies in the
      pathogenesis of paraneoplastic neurological disease remains uncertain.

PMID- 11239945
TI  - Dopamine supports sentence comprehension in Parkinson's Disease.
AB  - OBJECTIVE: To determine the role of dopamine in the executive resource component
      of sentence comprehension. METHODS: We studied sentence-picture matching in 20
      right-handed, non-demented, native English speakers with mild Parkinson's disease
      (PD) when 'on' and 'off' their levodopa, taking into account disease duration to
      control for endogenous dopamine metabolism. We also administered a verbal working
      memory measure that does not involve specific grammatical manipulations. RESULTS:
      PD patients 'off' levodopa demonstrated a significant discrepancy in their
      comprehension of grammatically complex sentences compared to grammatically
      simpler sentences that was not evident when PD patients were 'on' levodopa. An
      error analysis demonstrated that impaired comprehension of grammatically complex
      sentences when 'off' levodopa was associated with poorer performance on foils
      requiring working memory resources. Performance on an independent measure of
      verbal working memory correlated only with comprehension of grammatically complex
      sentences during levodopa supplementation, but working memory according to this
      measure did not differ during 'on' and 'off' states. CONCLUSION: Dopamine
      supports the executive resources contributing to sentence comprehension in PD.

PMID- 11239947
TI  - Visual evoked potential changes in migraine. Influence of migraine attack and
      aura.
AB  - OBJECTIVE: To assess the visual evoked potential (VEP) changes in migraines with
      and without aura. STUDY DESIGN: A clinical study in which the VEP results of 45
      migraineurs (study group) and 22 healthy volunteers (control group) were
      compared. Of 45 migraineurs, 29 had migraine with aura (MA) and 16 had migraine
      without aura (MOA), and they were examined both during and between the migraine
      attacks. METHODS: The patients and healthy controls underwent VEP assessment. On
      VEP recording, mono-ocular stimulation was performed by means of the pattern
      reversal check board. The latencies of N1, P1 and N2, and the N1--P1 amplitude
      were noted. The following comparisons were made between NI, P1 and N2 latencies
      and N1--P1 amplitudes of the migraine and control groups; during and between
      attack the VEP results of the patients with MA and MOA. RESULTS: The VEP results
      of the migraineurs and healthy controls were similar (P>0.05). The during attack
      results of MA, during and between attack results of MOA, and the results of the
      control group were also similar (P>0.05). N2 latency significantly elongated in
      patients with MA in the attack free period than it was during the attack
      (P=0.01), and was also longer than it was in the control group (P=0.01).
      CONCLUSIONS: There is involvement of the visual pathway in MA rather than MOA,
      and differentiation between these subtypes of the migraine disease may be
      performed on the basis of VEP findings manifesting by the prolongation of the N2
      wave latency. This contention should be confirmed by further studies.

PMID- 11239948
TI  - CTLA4 in multiple sclerosis. Lack of genetic association in a European Caucasian
      population but evidence of interaction with HLA-DR2 among Shanghai Chinese.
AB  - In the present study we searched for an association between multiple sclerosis
      (MS) and the gene encoding the cytotoxic T lymphocyte antigen 4 (CTLA4). Our
      experimental approach involved amplification of DNA fragments of the promoter and
      exon 1 of this gene containing single nucleotide polymorphisms followed by
      treatment of the amplified fragments with restriction enzymes for allele
      determination. Included in the study were 84 MS patients and 125 healthy control
      subjects from a population of white Caucasians. We also examined 42 MS patients
      and 86 healthy control subjects of Shanghai Chinese origin. Significant
      differences in the distribution of genotypes or haplotypes of the CTLA4 gene were
      not observed between MS patients and control subjects in either of the two
      populations (P>0.05). Moreover, we were not able to confirm a previous finding of
      an association between relapsing-remitting MS and the heterozygous genotype A/G
      of CTLA4 exon 1. There was no evidence to suggest that interaction between HLA
      DR2 and CTLA4 is involved in the development of MS among European Caucasians
      (P>0.05). Opposed to this, analysis of the Shanghai Chinese suggested presence of
      such interaction (P=0.02). Our results do not support the assumption that CTLA4
      influences susceptibility to MS in European Caucasians. On the other hand, they
      raise the possibility that the development of MS in other ethnic groups involves
      interaction between CTLA4 and DR2.

PMID- 11239949
TI  - A novel missense mutation in the early growth response 2 gene associated with
      late-onset Charcot--Marie--Tooth disease type 1.
AB  - A novel mutation (Arg381Cys) in the second zinc-finger domain of early growth
      response 2 (EGR2) was identified in a late-onset Charcot--Marie--Tooth disease
      type 1 (CMT1) patient. This patient had initial symptoms of numbness and weakness
      in the leg at age 59, and a median nerve motor conduction velocity of 27 m/s. A
      sural nerve biopsy showed a severe loss of myelinated fibers with numerous onion
      bulbs. This is the first report of the EGR2 mutation presenting a late onset of
      CMT1 phenotype. Its mutation was a different amino acid substitution at codon 381
      (Arg381His) which demonstrated congenital hypomyelinating neuropathy or early
      onset CMT1. This report suggests that the EGR2 mutation represents divergent
      phenotypes at codon 381, which may be a mutation hotspot.

PMID- 11239950
TI  - Magnetization transfer histogram parameters reflect all dimensions of MS
      pathology, including atrophy.
AB  - INTRODUCTION: Magnetization transfer ratio (MTR) histogram analysis can be used
      as a method for quantifying overall disease burden in MS. We studied correlations
      between MTR histogram and clinical parameters in MS subgroups. Contrary to
      earlier studies we placed special emphasis on the lower MTR range, to explore the
      effect of partial volume averaging effects with CSF. METHODS: Seventy-nine
      patients with MS [26 primary progressive (PP), and 53 'relapse-onset', including
      26 secondary progressive (SP)], and 23 healthy individuals were studied. MR
      imaging included 3 mm 2D gradient-echo images with and without an off-resonance
      MT pulse. According to the visually determined cut-off, histogram parameters were
      classified as parenchymal or CSF-related variables. Clinical measurements
      included the Expanded Disability Status Scale (EDSS) as a measure of global
      impairment/disability and the Paced Auditory Serial Addition Test (PASAT) as a
      measure of cognition. RESULTS: SP MS patients differed from the other subgroups
      on many MTR variables, originating from both the lower and the higher MTR range.
      CSF-related low MTRs were clearly over-represented in SP patients, and showed a
      significant distinction between the SP and PP MS group. In the total group, as
      well as in the relapse-onset patients, significant correlations were found
      between MTR parameters and clinical parameters. No associations were found in the
      PP group. CONCLUSION: This explorative study suggests that MTR histogram analysis
      can distinguish between MS patients and controls, and best identifies the SP
      phenotype, partly as a result of increased CSF volume (atrophy). In addition, we
      show that MTR histogram analysis gives information about the level of impairment
      and disability in patients with a 'relapse-onset' course of MS, and therefore
      provides a useful tool to monitor the evolution of the disease in these patients.

PMID- 11239952
TI  - Acute encephalitis from 1967 to 1991.
AB  - We studied all the adult patients with acute encephalitis, 322 in all, in the
      Helsinki area, Finland, during the years 1967--1991. The average incidence was
      1.4/100000 adults/year. The proportion of known and suggested etiologies in 5
      year periods has risen from 36 (1967--71) to 59% (1987--91). Herpes simplex virus
      was identified most often (16%), followed by varicella-zoster (5%), mumps (4%),
      and influenza A viruses (4%). In addition, 20 other agents were identified. The
      leading cause of encephalitis in patients aged 65 years or more was varicella
      zoster virus. Eighteen patients (5.6%) died. It appears that the etiology of
      encephalitis changes with age and with time. It is important to establish the
      etiological pattern, as this assists in prompt diagnosis, which is a prerequisite
      for successful therapy.

PMID- 11239951
TI  - Diffusion-weighted MRI in two cases of familial Creutzfeldt--Jakob disease.
AB  - Diffusion-weighted magnetic resonance imaging (DWI) has been described as a
      useful tool for the diagnosis of sporadic Creutzfeldt--Jakob disease (CJD). To
      our knowledge, DWI abnormalities have not previously been reported in familial
      CJD. In two patients with familial CJD associated with distinct mutations at
      codon 183 and at codon 210 of the prion protein gene, DWI showed a high signal in
      the basal ganglia and in the cerebral cortex. These abnormalities are similar to
      those described in sporadic CJD. This observation expands the value of DWI for
      the diagnosis of some forms of familial CJD. It remains to be investigated
      whether this finding also holds for CJD associated with other mutations of the
      prion protein gene.

PMID- 11239953
TI  - Paraoxonase 1 Met--Leu 54 polymorphism is associated with Parkinson's disease.
AB  - Two up-to-date known paraoxonase 1 (PON1) polymorphisms (Gln--Arg 191 and Leu-
      Met 54) affect the hydrolysis of toxic oxons and might intensify effects of
      pollutants, organophosphates and other environmental chemicals in development of
      Parkinson's disease (PD). We reported previously that PON1 G1n--Arg 191
      polymorphism did not influence on the susceptibility to PD. In the present study
      we have investigated the PON1 Leu--Met 54 polymorphism in 117 patients with
      sporadic idiopathic PD. A new approach for Leu--Met 54 polymorphism genotyping
      has been developed. We have showed the frequency of the Met 54 allele of PON1 to
      be significantly increased in patients with PD compared with the controls
      (chi(2)=8.63, df=1, P<0.003). The relative risk of PD in the Met 54 allele
      carriers has been estimated to be 2.3 fold higher than in homozygotes for the L
      allele. Moreover it appeared to be even 5.15 higher in the subgroup of patients
      with early-onset PD. We suggest that the Met 54 allele may be considered to be an
      independent risk factor for PD. This mutation could probably cause PON1 impaired
      metabolism of environmental neurotoxins and might be responsible for
      neurodegeneration.

PMID- 11239954
TI  - Autonomic dysfunction in experimental autoimmune neuritis: heart rate.
AB  - Autonomic nervous system (ANS) dysfunction occurs in more than half of Guillain-
      Barre syndrome (GBS) patients and is an important cause of death in the disease.
      In this study we examined heart rate (HR) changes in an animal model of GBS,
      experimental autoimmune neuritis (EAN), induced by immunization with myelin
      extracted from bovine spinal roots. The animals developed progressive motor
      weakness accompanied by significant weight loss and hypothermia. HR was measured
      in 33 EAN rats at rest (rHR) and followings stressful stimulation (sHR). Average
      pre-immunization rHR was 341+/-28 beats per minute (b.p.m.) and sHR was 486+/-21
      bpm. Although the mean rHR in rats with EAN was not significantly different
      compared to that at baseline, there was a significant increase of variation of
      rHR with six rats demonstrating bradycardia (<280 b.p.m.) and 10 tachycardia
      (>400 b.p.m.) (P<0.01, F-test). sHR in EAN rats was significantly lower (P<0.01),
      suggesting sympathetic system impairment. These findings may serve as a basis for
      testing treatments of ANS dysfunction in EAN.

PMID- 11239955
TI  - Multiple sclerosis with secondary syringomyelia. An autopsy report.
AB  - We report an elderly woman with multiple sclerosis who showed an extensive cavity
      formation in the midthoracic cord in addition to multiple abnormal intensity
      signals in the central nervous system on magnetic resonance imaging (MRI). The
      cavity decreased in size in response to corticosteroid therapy with an
      improvement in neurological symptoms. The autopsy demonstrated a slit-like cavity
      lined with no ependymal cells on the luminal surface in the lower cervical to
      midthoracic cord, with circumferentially distributed demyelinative lesions,
      leading to the pathological diagnosis of secondary syringomyelia. In this patient
      a limited necrosis formed in the spinal cord might have developed into a cavity
      formation with edematous fluid leading to subsequent episodes of neurological
      exacerbation.

PMID- 11239956
TI  - Increased anaerobic glycolysis in mitochondrial trifunctional protein-deficient
      brain.
AB  - Deficiency of mitochondrial trifunctional protein (TP), beta-oxidation enzyme, is
      characterized by recurrent rhabdomyolysis in adult patients. Positron emission
      tomography was used to measure brain oxygen (CMRO(2)) and glucose (CMRGlc)
      metabolisms in an adult patient with TP deficiency who had a homozygous G1331A
      transition of the beta-subunit gene. The molar ratio of oxygen to glucose
      consumption showed diffuse reduction; CMRO(2) was markedly decreased, whereas
      CMRGlc increased. Oxidative metabolism may be impaired and anaerobic glycolysis
      stimulated in the brain of this patient with TP deficiency.

PMID- 11239957
TI  - Spontaneous carotid dissection presenting lower cranial nerve palsies.
AB  - Cranial nerve palsy in internal carotid artery (ICA) dissection occurs in 3--12%
      of all patients, but in 3% of these a syndrome of hemicranias and ipsilateral
      cranial nerve palsy is the sole manifestation of ICA dissection, and in 0.5% of
      cases there is only cranial nerve palsy without headache. We present two cases of
      lower cranial nerve palsy. The first patient, a 49-year-old woman, developed left
      eleventh and twelfth cranial nerve palsies and ipsilateral neck pain. The angio
      RM showed an ICA dissection with stenosis of 50%, beginning about 2 cm before the
      carotid channel. The patient was treated with oral anticoagulant therapy and
      gradually improved, until complete clinical recovery. The second patient, a 38
      year-old woman, presented right hemiparesis and neck pain. The left ICA
      dissection, beginning 2 cm distal to the bulb, was shown by ultrasound scanning
      of the carotid and confirmed by MR angiogram and angiography with lumen stenosis
      of 90%. Following hospitalisation, 20 days from the onset of symptoms, paresis of
      the left trapezius and sternocleidomastoideus muscles became evident. The patient
      was treated with oral anticoagulant therapy and only a slight right arm paresis
      was present at 10 months follow-up. Cranial nerve palsy is not rare in ICA
      dissection, and the lower cranial nerve palsies in various combinations
      constitute the main syndrome, but in most cases these are present with the motor
      or sensory deficit due to cerebral ischemia, along with headache or Horner's
      syndrome. In the diagnosis of the first case, there was further difficulty
      because the cranial nerve palsy was isolated without hemiparesis, and the second
      case presented a rare association of hemiparesis and palsy of the eleventh
      cranial nerve alone. Compression or stretching of the nerve by the expanded
      artery may explain the palsies, but an alternative cause is also possible, namely
      the interruption of the nutrient vessels supplying the nerve, which in our
      patients is more likely.

PMID- 11239958
TI  - Fidelity of replication of repetitive DNA in mutS and repair proficient
      Escherichia coli.
AB  - Replication fidelity is not constant among strains within a species or at all
      genetic loci within a genome. Altered fidelity of replication may affect patterns
      of pathogenesis and the evolution of these strains. We have been studying
      replication fidelity in Escherichia coli, both in laboratory attenuated strains
      and in food-borne pathogens. To understand the altered patterns of mutagenesis at
      the molecular level, we used a shuttle vector plasmid with a tRNA mutational
      marker gene which had been altered to include homopolymeric runs of five, seven
      and nine [G:C] pairs, as well as non-repetitive DNA. Replication of the plasmid
      in mutS strains resulted in a 20-fold increase in mutant progeny plasmids. The
      mutations were almost all (>90%) frameshift mutations, while base substitution
      mutations were rare. Most mutations were insertions or deletions of one or two
      [G:C] pairs in the longest homopolymeric runs. Larger deletions (5 to >70bp),
      also targeted to the repetitive sequence, were likewise common. Mutations
      increased exponentially with the length of the homopolymeric run. These patterns
      of mutation, including unexpectedly high levels in repair proficient strains, led
      to an examination of the E. coli K-12 genome for homopolymeric DNA. This sequence
      motif was found to be rare, particularly in genes and open reading frames. Amino
      acid homotrimers were found to avoid usage of homopolymeric codons, even when
      they are preferred among synonymous codons in E. coli. There appears to be active
      selection against tandem direct nucleotide repeats in the E. coli genome,
      correlated with the inability of the organism to accurately replicate such
      sequence.

PMID- 11239959
TI  - Chromosomal instability in BRCA1- or BRCA2-defective human cancer cells detected
      by spontaneous micronucleus assay.
AB  - The BRCA1 and BRCA2 gene products are believed to play an important part in the
      onset and/or development of many sporadic mammary cancers. Recently, it has been
      reported that these two proteins contribute to a centrosome function which is
      believed to help maintain the integrity of the chromosome segregation process.
      This may mean a reduced level of the BRCA1 or BRCA2 protein in mammary cells will
      occasionally lead to nondisjunctional chromosomal loss or gain. We now report
      that spontaneous micronuclei arising from chromosome(s) which fail to be
      incorporated into the relevant daughter nuclei during mitosis tend to occur more
      frequently in BRCA1- or BRCA2-defective human cancer cells than in BRCA-positive
      cancer cells. Some cases of mammary carcinogenesis may therefore stem from the
      loss of integrity of chromosome segregation in cells which have a reduced
      capacity to express either BRCA1 or BRCA2.

PMID- 11239960
TI  - Salsolinol, a naturally occurring tetrahydroisoquinoline alkaloid, induces DNA
      damage and chromosomal aberrations in cultured Chinese hamster lung fibroblast
      cells.
AB  - Salsolinol (SAL) is a tetrahydroisoquinoline neurotoxin that has been speculated
      to contribute to pathophysiology of Parkinson's disease and chronic alcoholism.
      The compound is also found in certain beverages and food stuffs, including soy
      sauce, beer and bananas. Despite potential human exposure to SAL and its
      endogenous formation, little is known about the genotoxic or carcinogenic
      potential of this substance. In the present investigation, SAL induced DNA damage
      in cultured Chinese hamster lung (CHL) fibroblasts as assessed by single cell gel
      electrophoresis (Comet). CHL cells treated with SAL also exhibited higher
      frequencies of chromosomal aberrations than did vehicle-treated controls. Our
      recent study has revealed that SAL in combination with Cu(II) causes the strand
      scission in phiX174 supercoiled DNA [Neurosci. Lett. 238 (1997) 95]. In line with
      this notion, addition of cupric ion potentiated the DNA damaging and clastogenic
      activity of SAL. Antioxidant vitamins, such as Vitamin C and Vitamin E, and
      reduced glutathione inhibited clastogenicity of SAL, suggesting the involvement
      of reactive oxygen species (ROS) in SAL-induced DNA damage and genotoxicity in
      CHL cells.

PMID- 11239961
TI  - Oxidative stress is not an obligate mediator of disease provoked by mitochondrial
      DNA mutations.
AB  - With age, mitochondrial DNA mutations and oxidative stress increase, leading to
      the hypothesis that the production of reactive oxygen species causes the
      pathogenic effects of mitochondrial DNA mutations. We tested this hypothesis
      using transgenic mice that develop cardiomyopathy due to the accumulation of
      mitochondrial DNA mutations specifically in the heart. Surprisingly, the
      mechanism of pathogenesis does not involve increased oxidative stress. The
      amounts of DNA and protein oxidative adducts are not elevated in the transgenic
      heart. Neither are signs of increased oxidative stress detected by measurements
      of enzyme function or oxidative defense systems. Rather, we find that the
      mitochondrial DNA mutations induce a cytoprotective response including increases
      in the levels of Bcl-2 and Bfl-1, pro-survival proteins that inhibit apoptosis,
      and atrial natriuretic factor. Bcl-2 is elevated in nearly all cardiomyocytes
      before the onset of dilated cardiomyopathy. These results raise the possibility
      that a signaling pathway between the mitochondrion and the nucleus mediates the
      pathogenic effect of mitochondrial DNA mutations.

PMID- 11239962
TI  - A comparison of mutations induced by accelerated iron particles versus those
      induced by low earth orbit space radiation in the FEM-3 gene of Caenorhabditis
      elegans.
AB  - The fem-3 gene of Caenorhabditis elegans was employed to determine the mutation
      frequency as well as the nature of mutations induced by low earth orbit space
      radiation ambient to Space Shuttle flight STS-76. Recovered mutations were
      compared to those induced by accelerated iron ions generated by the AGS
      synchrotron accelerator at Brookhaven National Laboratory. For logistical
      reasons, dauer larvae were prepared at TCU, transported to either Kennedy Space
      Center or Brookhaven National Laboratory, flown in space or irradiated, returned
      to TCU and screened for mutants. A total of 25 fem-3 mutants were recovered after
      the shuttle flight and yielded a mutation frequency of 2.1x10(-5), roughly 3.3
      fold higher than the spontaneous rate of 6.3x10(-6). Four of the mutations were
      homozygous inviable, suggesting that they were large deletions encompassing fem-3
      as well as neighboring, essential genes. Southern blot analyses revealed that one
      of the 25 contained a polymorphism in fem-3, further evidence that space
      radiation can induce deletions. While no polymorphisms were detected among the
      iron ion-induced mutations, three of the 15 mutants were homozygous inviable,
      which is in keeping with previous observations that high LET iron particles
      generate deficiencies. These data provide evidence, albeit indirect, that an
      important mutagenic component of ambient space radiation is high LET charged
      particles such as iron ions.

PMID- 11239963
TI  - Relative biological efficiency for the induction of various gene mutations in
      normal and enriched with 10B Tradescantia cells by neutrons from 252Cf source.
AB  - The effectiveness of neutrons from a Californium-252 source in the induction of
      various abnormalities in the Tradescantia clone 4430 stamen hair cells (Trad-SH
      assay) were studied. A special attention was paid to check whether any
      enhancement in effects is visible in the cells enriched with boron ions.
      Inflorescences, normal or pretreated with chemicals containing boron, were
      irradiated in the air with neutrons from a 252Cf source at KAERI, Taejon, Korea.
      To estimate the relative biological effectiveness (RBE) of the beam under the
      study, numbers of Tradescantia inflorescence without chemical pretreatment were
      irradiated with various doses of X-rays. The ranges of radiation doses used for
      neutrons were 0-1.0Gy and for X-rays 0-0.5Gy. Following the culturing according
      to standard procedures screening of gene and lethal mutations in somatic cells of
      stamen hairs was done in the extended period, between days 7 and 19 after
      exposures. Maximal RBE values for the induction of pink, colorless and lethal
      mutations were evaluated from comparison of the slopes in linear parts of the
      dose response curves obtained after irradiation with X-rays and californium
      source. The RBE(max) value or the induction of gene mutation was estimated as 7.2
      comparing the value 5.6 in the studies reported earlier. The comparison of dose
      response curves and its alteration, due to changes in the cells and plants
      environment during and after irradiation, explains the observed differences.
      Inflorescence pretreated with borax responded to neutrons differently depending
      on the biological end points. Although, for the induction of pink mutations no
      significant difference was observed, though, in the case of cell lethality,
      pretreated with boron ion plants have shoved a statistically significant increase
      of the RBE value from 5.5 to 34.7, and in the case of colorless mutations from
      1.6 to 5.6.

PMID- 11239964
TI  - Antimutagenic activity of green tea and black tea extracts studied in a dynamic
      in vitro gastrointestinal model.
AB  - An in vitro gastrointestinal model, which simulates the conditions in the human
      digestive tract, was used to determine potential antimutagenic activity of
      extracts of black tea and green tea. In this paper, results are presented on the
      availability for absorption of potential antimutagenic compounds present in tea
      and on the influence of the food matrix on this activity. Between 60 and 180min
      after the tea was introduced into the model, antimutagenic activity was recovered
      from the jejunal compartment by means of dialysis: the dialysate appeared to
      inhibit the mutagenicity of the food mutagen MeIQx in the direct plate assay with
      Salmonella typhimurium (Ames test). The maximum inhibition was measured at 2h
      after the start of the experiment and was comparable for black tea and green tea
      extract. To determine the influence of food matrices on the antimutagenic
      activity of tea, the model was loaded with black tea together with milk or a
      homogenized standard breakfast. The maximum inhibition observed with black tea
      was reduced by 22, 42 and 78% in the presence of whole milk, semi-skimmed milk,
      and skimmed milk, respectively. Whole milk and skimmed milk abolished the
      antimutagenic activity of green tea by more than 90%; for semi-skimmed milk the
      inhibition was more than 60%. When a homogenized breakfast was added into the
      model together with the black tea extract, the antimutagenic activity was
      completely eliminated. When tea and MeIQx were added together into the digestion
      model, MeIQx mutagenicity was efficiently inhibited, with green tea showing a
      slightly stronger antimutagenic activity than black tea. In this case, the
      addition of milk had only a small inhibiting effect on the antimutagenicity.
      Antioxidant capacity and the concentration of catechins were also measured in the
      jejunal dialysates. The reduction in antimutagenic activity corresponded with
      reduction in antioxidant capacity and with a decrease of concentration of three
      catechins, viz. catechin, epigallocatechin gallate and epigallocatechin. The in
      vitro gastrointestinal model appears to be a useful tool to study the
      antimutagenicity of food components.

PMID- 11239965
TI  - Comparison of the protective effect of melatonin with other antioxidants in the
      hamster kidney model of estradiol-induced DNA damage.
AB  - 17beta-Estradiol (E(2)) is a known carcinogen. Estrogen induction of tumors in
      hamster kidney is a model of estrogen-related carcinogenesis. Melatonin is a well
      known antioxidant, free radical scavenger and oncostatic agent. Changes in the
      levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), an index of DNA
      damage, were measured in kidneys, liver and testes from hamsters treated with
      E(2) (75mg/kg b.w.) and collected 5h later. Potential protective effects of
      melatonin, N-acetylserotonin (NAS), indole-3-propionic acid (IPA) and ascorbic
      acid (AA) against E(2)-induced DNA damage were tested. The antioxidants were
      applied in equimolar doses of 64.5 micromol/kg b.w., 2 and 0.5h before and 2 and
      4h after E(2) treatment. E(2) treatment caused a significant increase in 8
      oxodGuo levels in kidneys, but did not influence significantly the oxidation of
      guanine bases in liver and testes. Melatonin, IPA and AA, but not NAS, completely
      prevented E(2)-induced DNA damage in hamster kidneys. It is concluded that
      melatonin, IPA and AA may be effective in protecting against E(2)-related DNA
      damage and, consequently, carcinogenesis.

PMID- 11239966
TI  - Activation of Ty transposition by mutagens.
AB  - The induction of Ty1 transposition by mutagens (MMS and 4NQO) in asynchronous
      cultures and cells blocked in G1 and G2/M suggested G1 dependence of activation
      of Ty1 element by DNA damage. Northern blot analysis revealed immediate five-fold
      increase in levels of Ty1 transcript after 20min incubation of cells with 1
      microg/ml 4NQO and four-fold increase in Ty1 RNA after treatment the cells with
      0.1% MMS. Western blot analysis showed no difference in TyA protein in treated
      and untreated with mutagen cells. Quantitative mutagenicity assay and Northern
      blot analysis demonstrated dependence of induction of Ty1 element by DNA-damaging
      agents on the function of RAD9 gene and independence on DUN1 gene.

PMID- 11239967
TI  - Differential sensitivity of murine myeloid FDC-P1 cells and apoptosis resistant
      mutant(s) to anticancer drugs.
AB  - There is growing evidence which suggests that dysregulation of apoptosis may lead
      to several disease states including cancer. To investigate the mechanism
      controlling the induction of cell death, apoptosis defective/resistant (Apt-)
      mutants were isolated and characterized in this study. FDC-P1, a mouse myeloid
      cell line that depends upon IL-3 for survival and growth but undergoes apoptosis
      when deprived of growth factor, was mutagenized by treatment with ethyl methane
      sulfonate. We selected cells that survived the growth factor deprivation but did
      not grow without the factor. Surviving cells were cloned by limiting dilution and
      four clones that showed the least morphological characteristics and biochemical
      changes of apoptosis were chosen. Unlike the parent FDC-P1, these mutants were
      cross resistant to apoptosis induced by a variety of antitumor drugs such as
      Adriamycin, Dexamethasone, VP-16, as well as reactive oxygen species (ROS)
      generated by xanthine/xanthine oxidase (X/XO). We used one of these Apt- mutant
      to test candidate death genes. Our findings suggest that the preferential
      increase in Bax/Bcl-2 ratio, p53, c-Myc, Caspase-3 and decrease in AP-1 on
      treatment with various anticancer drugs may contribute to the preferential
      apoptotic response in FDC-P1 cells but to varying degrees. Whereas, the higher
      constitutive level of antioxidant enzymes superoxide dismutase and catalase in
      the Apt- mutant may contribute at least in part to its resistance.

PMID- 11239968
TI  - Structure-antimutagenic activity relationships of benzalacetone derivatives
      against UV-induced mutagenesis in E. coli WP2uvrA and gamma-induced mutagenesis
      in Salmonella typhimurium TA2638.
AB  - The antimutagenic activities of benzalacetone (4-phenyl-3-buten-2-one) and its
      structurally-related compounds were evaluated through their use as post
      treatments for the UV-induced mutagenesis in Escherichia coli WP2s (uvrA) and the
      gamma-induced mutagenesis in Salmonella typhimurium TA2638, the latter of which
      is sensitive to oxidants. Structure-activity relationships were studied between
      IC(50) activity values, i.e. the dose (micromol/ml) at which the mutation
      frequency is reduced to 50% of the control, and electronic and hydrophobicity
      properties of the studied molecules. Benzalacetone and benzalacetone analogs,
      cinnamaldehyde and trans-1,1,1-trifluoro-4-phenyl-3-buten-2-one (TF), inhibited
      both forms of mutagenesis, but methyl cinnamate, cinnamic acid and cinnamamide
      did not. The IC(50) values of TF, for UV-induced mutagenesis and gamma-induced
      mutagenesis, were 0.028 and 0.045 micromol/ml, respectively, and one order of
      magnitude lower than those of cinnamaldehyde and benzalacetone. The three
      antimutagenic analogs listed in order of decreasing activity are:
      TF>>cinnamaldehyde>benzalacetone. This order is proportional to the electron
      withdrawing property of the terminal group attached to an alpha,beta-unsaturated
      carbonyl moiety in the side chain that is known to play an important role in the
      antimutagenicities of benzalacetone and related compounds. In UV-induced
      mutagenesis in E. coli WP2s, mono-substituted benzalacetones - the ring
      substituents of which have electron-withdrawing properties - showed antimutagenic
      activity that correlated with their electronic property. In gamma-induced
      mutagenesis in S. typhimurium TA2638, the antimutagenic activities of mono
      substituted benzalacetones were proportional to the substituent hydrophobicities
      (pi). The different effects on both the mutation-induced systems is suggested to
      be related to the relative permeability of the cell membranes and the different
      sensitivities to mutagens between E. coli WP2s and S. typhimurium TA2638. In
      addition, the antimutagenic activity against gamma-induced mutagenesis could be
      due to the ability of parent compounds or their derivatives to scavenge long
      lived organic radicals; the radicals have been described to be generated as a
      result of the X-irradiation of cells by Koyama et al. [Mutat. Res. 421 (1998)
      45].

PMID- 11239969
TI  - The effect of smoking and eating habits on DNA damage in Indian population as
      measured in the Comet assay.
AB  - This study was undertaken with the aim of assessing the status of DNA damage in a
      normal healthy Indian population. The 62 male volunteers in this study belonged
      to the smoking, non-smoking, vegetarian and non-vegetarian categories, were well
      educated and aged between 23 and 57 years. The data revealed significant
      differences in the extent of DNA damage in the smokers versus non-smokers as well
      as between the vegetarians and non-vegetarians. A significant difference was also
      observed amongst the different groups of smokers depending on the extent of
      smoking. An age-dependent effect in DNA damage was also observed. This
      preliminary study has, for the first time, revealed differences in the extent of
      DNA damage in the normal Indian population depending on their eating and smoking
      habits as well as age.

PMID- 11239970
TI  - Evaluation of the genotoxicity of the phytoestrogen, coumestrol, in AHH-1 TK(+/-)
      human lymphoblastoid cells.
AB  - Coumestrol, a phytoestrogen found in high levels in alfalfa and red clover, is of
      concern since endocrine disorders have been observed in farm animals exposed to
      high levels of phytoestrogens. Previous studies found that coumestrol was an
      effective inducer of DNA strand breaks, micronuclei, and mutations in the
      Hypoxanthine phosphoribosyl transferase (HPRT) gene of Chinese hamster ovary
      cells. In the experiments presented here, we extended the previous studies to
      examine the effect of coumestrol exposure on AHH-1 TK(+/-) human lymphoblastoid
      cells. Micronuclei were induced with the highest frequency occurring at day 2
      after exposure. Flow cytometric analysis of annexin V-FITC-7-aminoactinomycin D
      stained cells indicated that the primary pathway of cell death was by apoptosis.
      Mutations were induced in the Thymidine Kinase (TK) gene and were due primarily
      to the induction of clones with the slow-growth phenotype. Subsequent molecular
      analysis revealed the loss of exon 4 in the coumestrol-induced clones, indicative
      of loss-of heterozygosity and consistent with a proposed inhibition of
      topoisomerase-II activity as a mechanism of action for coumestrol. Taken
      together, these results suggest that coumestrol exhibits both mutagenic and
      clastogenic properties in cultured human lymphoblastoid cells.

PMID- 11239971
TI  - In vitro transmission of chromosomal aberrations through mitosis in human
      lymphocytes.
AB  - Stable and unstable chromosome aberrations in human lymphocytes exposed to 2 and
      4Gy of X-rays in G(0) were analyzed in M1 and M2 cells harvested at 72h to
      investigate how the scoring protocol influences the yields of aberrations
      transmitted through one mitosis. Metaphase chromosomes 2, 3, and 5 were painted
      using fluorescence in situ hybridization (FISH) whole chromosome probes, together
      with a pan-centromeric probe and stained by the harlequin-FISH method, to allow
      the cell cycle status of each cell to be determined as it was scored. A strict
      scoring criterion was adopted so that each metaphase had to contain 46
      centromeres and each dicentric/centric ring had to have an acentric present. In
      addition to scoring the painted material, unstable aberrations in the whole
      genome were also recorded. The yield of complete dicentrics decreased by more
      than a factor of 2 in going from M1 to M2. The decrease was greater at the lower
      dose. Two-way translocations appeared stable, but one-way translocations
      decreased. This suggests that if translocation yields are to be used for
      biological dosimetry purposes, then the two-way type should be used.

PMID- 11239973
TI  - Polar alteration of short tandem repeats (STRs) in mammalian cells.
AB  - Instability of short tandem repeats (STRs) in DNA during replication is observed
      in all organisms examined, and is causatively involved in various human diseases.
      We explore the mechanisms involved in instability by examining length changes
      occurring during the replication of [(CA)(20)TA](n) and [(CAG)(20)TAG](n), in
      human cells. We show that the majority of alterations consist of an insertion or
      deletion of one repeat unit, and base substitutions or length changes involving
      many repeat units are rare. We also show that length changes of two-tract STRs
      are biased toward the 3'-end of the repeat tract, in reference to lagging strand
      synthesis. There are some differences between our observations and previous
      observations in microbes, e.g. the orientation effect was not observed in this
      study. The results of this study are discussed in terms of the molecular
      mechanisms leading to alterations in repeat tracts.

PMID- 11239972
TI  - Analysis of mutational effects at the HPRT locus in human G(0) phase lymphocytes
      irradiated in vitro with gamma rays.
AB  - The mutational effects of ionising radiation at the hypoxanthine-guanine
      phosphoribosyl transferase (HPRT) locus were studied in human peripheral blood
      G(0) phase lymphocytes irradiated in vitro with gamma rays. The presence of
      radiation induced mutants was assessed by selecting the HPRT mutants every week
      on the basis of 6-thioguanine resistance up to 1 month after irradiation. A dose
      related increase of 14.25x10(-6) mutants/Gy was measured after an expression time
      of 7 days. After 2 weeks from culture starting the fraction of clonable cells in
      irradiated and control cell populations decreased, limiting the measurements of
      mutant frequency. The mutational spectrum of the HPRT gene was determined by PCR
      analyses in a total of 99 mutant clones derived from irradiated lymphocytes. The
      independent origin of mutant clones carrying the same mutation was assessed by
      analysing the TCR gamma gene rearrangements. The results showed a dose-related
      increase of deletion mutants up to 3Gy, whereas point mutation frequency
      increased only up to 2Gy. Two preferentially deleted regions were identified; one
      involving the HPRT exon 3, and another one the 3'-terminal and the 3'-flanking
      region of the gene. One complex mutation involving a non-contiguous deletion of
      exons 2-5 and 7/8 was observed among the mutants isolated after 3Gy irradiation.

PMID- 11239974
TI  - Release of endogenous cholecystokinin in response to gastric preloads in rats on
      postnatal days 9--12.
AB  - Release of endogenous cholecystokinin (CCK) from the small intestine by gastric
      loads was investigated in rats on postnatal days 9--12 (P9--P12). After 5--6 h of
      deprivation, pups received 5% b.wt. loads of water, 0.9% NaCl, 20% glucose, 20%
      maltose, 200 mg soybean trypsin inhibitor (SBTI) in 0.9% saline or sham load.
      Plasma was collected 15 min after the loads, and the concentration of bioactive
      CCK was measured by a specific and sensitive bioassay. Loads of SBTI and water
      significantly increased plasma CCK compared to sham loads, but loads of saline,
      glucose, and maltose did not. The efficacy of the water load was not demonstrated
      in adult rats. The results suggest that the previously reported reduction of
      intake during independent ingestion by hypertonic preloads of glucose and maltose
      was not mediated by the release of CCK sufficient to be detected in the plasma
      under these conditions.

PMID- 11239975
TI  - Meal palatability, substrate oxidation and blood glucose in young and older men.
AB  - We investigated the effects of food palatability on the thermic effect of feeding
      (TEF), substrate oxidation and circulating glucose and insulin. Healthy young men
      (23.4+/-1.0, SD, years, n=10) and older men (69.4+/-1.3, years, n=9) were
      resident in a metabolic unit for two 2-day study periods. On the second day of
      each period, they consumed in random order either a palatable test meal
      containing 2.93 MJ or a nonpalatable control meal containing the same foods in
      identical amounts but blended and freeze-dried into biscuit form. TEF and
      respiratory quotient (RQ) were measured over 6 h and blood samples were taken for
      measurement of glucose and insulin. Age group had no effect on TEF, RQ or
      circulating glucose other than to delay the time of peak TEF (P<0.002 for both
      meals). There was no significant effect of meal type on TEF, but RQ and
      circulating glucose were higher following consumption of the palatable meal
      (P<0.001 for both parameters). These results suggest that over 6 h postprandial,
      consumption of palatable foods does not increase TEF, but is instead associated
      with increased glycemic response and increased carbohydrate oxidation. These
      changes, combined with previous work on the glycemic index, predict an
      accelerated return of hunger and increased energy intake at subsequent meals
      following consumption of palatable vs. control foods. Further studies are needed
      to examine the possible mechanism for this previously suggested "second meal"
      effect of diet palatability on energy intake.

PMID- 11239976
TI  - Selectively bred male rat lines differ in naive and experienced sexual behavior.
AB  - Ejaculatory behavior is facilitated by activating 5-hydroxytryptamine(1A) (5
      HT(1A)) receptors. The present study examined male sexual behavior in rat lines
      that were selectively bred for their different hypothermic responses to 8-hydroxy
      2-(di-n-propylamino)tetralin (8-OH-DPAT). Sexual behavior was examined in naive
      and experienced HDS (high 8-OH-DPAT sensitive), LDS (low 8-OH-DPAT sensitive),
      and RDS (randomly bred) rats lines. In addition, the effects of 8-OH-DPAT (0.05
      mg/kg) and N-(2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-(2-pyridinyl)
      cyclohexane-carboxamide (WAY 100,635; 1 mg/kg) were examined. Naive HDS animals
      had diminished ejaculatory behavior (as indicated by a decreased number of
      intromissions, mounts and ejaculations, increased ejaculation and intromission
      latency, and longer inter-copulatory interval), compared to the LDS and RDS
      groups. In addition, the post-ejaculatory interval (PEI) was longer in the HDS
      group. With experience, the HDS group improved its ejaculatory behavior.
      Experienced HDS animals had a lower number of intromissions and a longer PEI
      compared to the LDS group. 8-OH-DPAT facilitated ejaculatory behavior in both HDS
      and LDS groups. This effect was more pronounced in the LDS group. WAY 100,635 did
      not alter sexual behavior in either group. In summary, alteration in forebrain 5
      HT(1A) receptors in HDS animals may be involved in the ability of naive rats to
      achieve ejaculation. 5-HT(1A) receptors are involved in the regulation of
      resumption of sexual behavior after ejaculation.

PMID- 11239977
TI  - Sleep detection with an accelerometer actigraph: comparisons with
      polysomnography.
AB  - Two validation studies were conducted to optimize the sleep-detection algorithm
      of the Actillume. The first study used home recordings of postmenopausal women
      (age range: 51 to 77 years), which were analyzed to derive the optimal algorithm
      for detecting sleep and wakefulness from wrist activity data, both for nocturnal
      in-bed recordings and considering the entire 24 h. The second study explored the
      optimal algorithm to score in-bed recordings of healthy young adults (age range:
      19 to 34 years) monitored in the laboratory. In Study I, the algorithm for in-bed
      recordings (n=39) showed a minute-by-minute agreement of 85% between Actillume
      and polysomnography (PSG), a correlation of.98, and a mean measurement error (ME)
      of 21 min for estimates of sleep duration. Using the same algorithm to score 24-h
      recordings with Webster's rules, an agreement of 89%, a correlation of.90, and 1
      min ME were observed. A different algorithm proved optimal to score in-bed
      recordings (n=31) of young adults, yielding an agreement of 91%, a correlation
      of.92, and an ME of 5 min. The strong correlations and agreements between sleep
      estimates from Actillume and PSG in both studies suggest that the Actillume can
      reliably monitor sleep and wakefulness both in community-residing elderly and
      healthy young adults in the laboratory. However, different algorithms are optimal
      for individuals with different characteristics.

PMID- 11239978
TI  - The effects of acute and chronic stress on motor and sensory performance in male
      Lewis rats.
AB  - Any behavioral testing induces stress to some degree. A meaningful interpretation
      of behavioral results can be difficult if stress, caused by handling or the
      testing situation, modifies the experimental outcome. Especially for neurological
      animal models, it is important to know how stress affects motor and sensory
      performance. Therefore, we investigated the effects of varying degrees of stress
      on several motor and sensory tasks that are frequently used to assess functional
      recovery after lesion-induced impairments in adult rats. Acute, subchronic, and
      chronic stress impaired ladder walking and prolonged the duration of grasping a
      bar. Stress also altered walking patterns by increasing the base of support and
      foot rotation and reducing stride length. Furthermore, chronic stress induced
      hypersensitivity to painful stimuli, but did not significantly influence the
      latency to remove sticky papers from the hindpaws (sticky paper test). In the
      light--dark (L/D) test, stress reduced the latency to enter the dark compartment
      and enhanced the number of transitions supporting that cold swim stress modifies
      the animal's level of anxiety. These data point towards a critical influence of
      acute or chronic stress on motor control and sensory performance of rats,
      suggesting that stress might be a critical intervening variable of the outcome of
      behavioral tests.

PMID- 11239979
TI  - Taste, intake rate, and food choice in rats.
AB  - The contribution of taste to the food choices of foraging rats was examined. Rats
      in a laboratory foraging paradigm searched for sequential opportunities to eat at
      two feeders containing chow-based food pellets that were plain or flavored with
      saccharin or citric acid. Pellets cost the same number of bar presses at both
      feeders. Saccharin adulteration had no effect on intake parameters. Citric-acid
      flavored pellets were eaten more slowly and in smaller meals. If there was no
      alternative food, daily intake was slightly reduced. When the alternative food
      was plain, fewer meals and fewer pellets were taken of the citric-acid-flavored
      than plain pellets. When we gradually increased the price of the plain pellets at
      one feeder, while the price at the alternative feeder (which contained either
      plain or citric-acid-flavored pellets) remained low, the rate of eating
      (profitability) decreased at the higher-price feeder, and the rats shifted their
      intake toward the less-costly, more profitable pellets. We compared the
      relationship between the relative eating rate at each feeder and the relative
      meal size (or daily intake) at each feeder when the low-priced food was plain and
      when it was flavored with citric acid, and found no differences. This indicates
      that taste may influence choice via its effect on rate of intake.

PMID- 11239980
TI  - Alarm pheromone enhances stress-induced hyperthermia in rats.
AB  - Behavioral and physiological effects of alarm pheromones emanating from stressed
      conspecific animals were investigated. Experimentally naive male Wistar rats were
      exposed to the test chambers containing alarm pheromones, which had been released
      by other rats receiving foot shocks in the same chamber beforehand. Along with
      behavioral analysis, the heart rate (HR) and core body temperature (cBT) were
      measured simultaneously using a biotelemetory system. Exposure to the alarm
      pheromones increased freezing, sniffing and walking and decreased resting as
      compared with rats exposed to control odors. In addition, these pheromone-exposed
      animals showed consistent increases in body temperature, i.e., stress-induced
      hyperthermia. After exposure to the alarm substances, immunoreactivity to nuclear
      Fos protein in the mitral cell layer in the accessory olfactory bulb (AOB) also
      increased compared with the reaction to control odors. These results suggest that
      an alarm pheromone enhances stress responses of conspecific animals both
      behaviorally and physiologically, and that these effects are mediated via
      activation of the AOB.

PMID- 11239981
TI  - The analysis of odor mixtures by humans: evidence for a configurational process.
AB  - Humans have a limited capacity to analyze odor mixtures with three to four being
      the maximum [Physiol Behav 46 (1989) 809.]. This study investigates the large
      loss of information about odor identity that occurs in mixtures and aims to
      determine the information on which identification and failure to identify is
      based. In Experiment 1, 14 subjects used a selective attention procedure to
      identify odorants in stimuli consisting of one to four components. As expected,
      substantial difficulties were encountered in identifying more than two odorants,
      and chance level scores were obtained for the group for each of the odorants in
      the quaternary mixture. In Experiment 2, 21 subjects used a profiling procedure
      consisting of 146 descriptors to describe the odor qualities perceived in the
      same stimuli used in Experiment 1. The results indicated that for some odorants,
      loss of a major characteristic quality occurred even in binary mixtures, but that
      many of the features of some odorants remained in the quaternary mixture.
      Comparison of the data from the two experiments indicated that identification of
      most of the prominent qualities of an odorant was not necessarily sufficient for
      identification of the odorant in a mixture. In contrast, the loss of some
      prominent features did not always result in non-identification. A configurational
      hypothesis of olfaction, analogous to that for facial and object recognition, is
      proposed to account for the data and the processes underlying odor identification
      in mixtures.

PMID- 11239982
TI  - The inhibition of nitric oxide synthase suppresses LPS- and psychological-stress
      induced fever in rats.
AB  - The purpose of this study was to assess the effects of a non-selective nitric
      oxide synthase (NOS) inhibitor on changes in fever response due to injection of
      lipopolysaccharide (LPS) or on stress fever caused by exposure to an open field
      in freely moving biotelemetered rats. N(omega)-nitro-L-arginine methyl ester (L
      NAME), an inhibitor of all NOS-isoforms, was injected intraperitoneally (ip) at a
      dose of 50 mg/kg just before intraperitoneal injection of LPS at a dose of 50
      microg/kg or exposure to open field. L-NAME at a dose of 50 mg/kg had no effect
      on normal day-time body temperature (T(b)) and normal night-time T(b). The same
      dose of L-NAME administered intraperitoneally caused a significant attenuation of
      LPS-induced fever. The thermal index calculated for rats pretreated with L-NAME
      and injected with LPS was reduced by approximately 75% compared to that
      calculated for saline-pretreated and LPS-injected rats. To examine the effect of
      NOS inhibition on psychological-stress-induced elevation in T(b), rats were
      injected intraperitoneally with L-NAME and then immediately exposed to open field
      for 60 min. After exposure to the open field, rats not treated with NOS inhibitor
      responded with a rapid rise in T(b), and it was accompanied with an increase of
      motor activity. L-NAME significantly suppressed the stress fever without any
      effect on changes in motor activity. Presented data provide clear evidence that
      NO formation is involved in LPS- and psychological-stress-induced fevers in rats.

PMID- 11239983
TI  - Plasma oxytocin and cortisol concentrations in dairy cows in relation to feeding
      duration and rumen fill.
AB  - The aim of this study was to investigate if the release of oxytocin and cortisol
      were different depending on levels of oral manipulation with feed or rumen fill
      in dairy cows. Blood samples and behavior of 12 rumen-fistulated cows were
      analyzed in 2 consecutive years during morning and afternoon periods when the
      cows were subjected to either (A) long duration of oral manipulation of feed with
      low rumen fill or (B) short duration of oral manipulation of feed but with filled
      rumen. The response areas under the curve for oxytocin in both years were larger
      in A than in B in the afternoons. There were peaks in oxytocin release at milking
      in the afternoon in both treatments. In B, the oxytocin concentration was higher
      after than before feeding, higher in B than in A after the non-oral rumen
      filling, and higher in B after than before the non-oral rumen filling in Year 1.
      The level of cortisol was higher in B than in A in the morning, lower in both
      treatments before than after milking in the afternoon, and there was a tendency
      for the cortisol level to be higher in A than in B after oral feeding. The B cows
      spent a shorter time eating and the A cows spent a shorter time ruminating. This
      study indicates that a long duration of oral manipulation of feed in cows, may,
      per se be linked to higher oxytocin but lower cortisol levels, compared with
      shorter oral feeding time and filled rumen.

PMID- 11239984
TI  - Acute hypoglycemia impairs the functioning of the central but not peripheral
      nervous system.
AB  - Acute hypoglycemia impairs functions of the central nervous system, but few
      controlled studies have assessed the impact of hypoglycemia on the function of
      the peripheral nervous system. Sixteen non-diabetic humans underwent two separate
      hyperinsulinemic glucose clamp procedures on different study days, in a counter
      balanced fashion. On one occasion, euglycemia was maintained (blood glucose, 5.0
      mmol l(-1)), and on the other occasion, hypoglycemia (blood glucose, 2.6 mmol l(
      1)) was induced. During each condition, subjects performed a combined
      psychometric, cognitive-experimental and psychophysical test battery, and
      measures were made (in the dominant median and common peroneal nerves) of the
      motor nerve conduction velocities and the amplitudes of the motor action
      potentials. Hypoglycemia caused impaired performance of general cognitive and
      information processing tasks (P<.05), but nerve conduction velocities and the
      amplitudes of motor action potentials were unaffected. Conduction velocities of
      the common peroneal nerve decreased from baseline within each experimental
      condition, perhaps due to hyperinsulinemia. Overall, these results demonstrate
      that multiple levels of information processing in the brain may alter while
      peripheral nerve function remains intact, and imply that peripheral neurons do
      not have the same obligate requirement for glucose as a metabolic fuel as neurons
      of the central nervous system.

PMID- 11239985
TI  - Dexamethasone suppression test using saliva cortisol measurement in bulimia
      nervosa.
AB  - The assessment of cortisol in saliva has been proven a valid and reliable
      reflection of the respective unbound hormone in blood. In the present study, a
      standard dexamethasone suppression test (DST) with measures of salivary cortisol
      levels was performed in bulimic women without depression (DSM-IV; N=48) and
      healthy controls (N=24) matched for age. Feedback sensitivity was assessed using
      the standard DST with pre- and post-measures of salivary cortisol. Subjects were
      divided into suppressors and nonsuppressors according to their post-DST levels.
      Bulimic suppressors and nonsuppressors were compared for their basal cortisol
      levels, body weight (body mass index, BMI), previous episodes of anorexia
      nervosa, and their results in psychometric tests. A total of 16 (33.3%) out of 48
      women with bulimia nervosa (BN) failed to suppress in the DST. Basal salivary
      cortisol levels were elevated in bulimic nonsuppressors. Significant differences
      between suppressors and nonsuppressors were found for body weight and previous
      episodes of anorexia nervosa. The results are in accordance with recent findings.
      They support the hypothesized association between low body weight and DST
      nonsuppression. Using saliva cortisol in the standard DST could be advantageous
      for studying bulimic patients. Furthermore, the results show the importance of
      determining HPA reagibility when measuring cortisol in bulimic patients.

PMID- 11239986
TI  - Influence of circadian phase and test illumination on pre-clinical models of
      anxiety.
AB  - Pre-clinical models of anxiety, particularly the elevated plus-maze (EPM), have
      been shown to be sensitive to a variety of methodological variations. Recent
      research has implicated circadian phase of testing in influencing the behavioural
      profile of 5-HT(1A) ligands on the EPM. The present study investigated the
      effects of testing animals during the dark and light phases and in light and
      subjective dark test conditions on baseline behaviour in animal models of
      anxiety. Eighty singly housed male Sprague-Dawley rats were exposed to a battery
      of unconditioned, exploratory tests (EPM, open field arena, holeboard) and a new
      model of extreme anxiety, the unstable elevated exposed plus-maze (UEEPM).
      Circadian phase of testing failed to consistently alter behaviour on any model.
      Level of test illumination had no effect on subjects' response to the open field
      arena, holeboard or UEEPM. Dark testing increased locomotor activity on the EPM
      (total arm entries, closed arm entries and distance moved) without decreasing
      open-arm avoidance. The construct of anxiety as measured by a number of different
      paradigms withstood major intra-laboratory manipulation of circadian phase of
      testing and illumination of apparatus. It is suggested that the effects of
      circadian rhythmicity may be confined to the behavioural profiles of
      serotonergic, particularly 5-HT(1A), ligands on the EPM.

PMID- 11239987
TI  - Allogeneic recombinant soluble MHC class I molecules modify urinary odor cues in
      rats.
AB  - The highly polymorphic genes of the major histocompatibility complex (MHC)
      determine, in part, the odor cues and behavior of an individual. In animal
      models, MHC-associated odors that regulate distinct behavior have been identified
      mainly in urine. However, the underlying mechanism is still not clear. Here, we
      show that injected recombinant soluble (rs) MHC class I molecules (DA, rsRT1.A(a)
      and Lewis, rsRT1.A(l)) temporarily alter urine odor of Lewis test rats
      (RT1.A(l)). This change in urinary signals was observed in behavioral assays
      using the habituation/dishabituation test and in odor signals analysed by gas
      chromatography (GC) and mass spectrometry (MS). Gas chromatographic analysis
      revealed that these altered odor signals are caused by quantitative changes of at
      least two nitrogen-containing urinary compounds. The results suggest that urinary
      olfactory cues are directly or indirectly influenced by MHC class I gene
      products.

PMID- 11239988
TI  - Hippocampal AgNOR activity after chronic alcohol consumption and alcohol
      deprivation in rats.
AB  - Chronic alcohol consumption induces morphological changes in the central nervous
      system and withdrawal does not reverse these changes. It is well known that the
      hippocampal formation is one of the brain regions most sensitive to prolonged
      alcohol ingestion. The aim of our study was to evaluate the transcriptional
      neuronal activity by measuring the argyrophilic nucleolar organizer regions
      (AgNORs) in the dentate gyrus, CA3, and CA1 hippocampal areas from adult male
      rats receiving chronic administration of ethanol (ALC) and after withdrawal
      (WDL). The parameters evaluated were the number and area of AgNORs, together with
      the area of nucleus and the proportion between AgNOR and nuclear areas (ratio).
      The animals from ALC and WDL groups showed a reduction in the number of AgNOR per
      cell as compared to the control group. CA3 was the hippocampal area most affected
      by chronic alcohol intake. No improvement was observed in animals after
      withdrawal. Our data support the idea that the chronic intake of alcohol
      decreases protein synthesis in hippocampal neurons at an early age. This decrease
      may explain the memory impairment showed by rats receiving chronic treatment with
      alcohol because, both in humans and rats, it is associated with a reduction in
      the number of cholinergic neurons in the basal forebrain that would in turn
      affect the hippocampal function.

PMID- 11239989
TI  - Leptin amplifies the feeding inhibition and neural activation arising from a
      gastric nutrient preload.
AB  - Leptin affects food intake by reducing meal size, suggesting that it may modulate
      the efficacy of within-meal satiety signals. To assess whether leptin would
      amplify the feeding inhibitory actions of a nutrient gastric preload, we compared
      liquid diet food intake and patterns of c-Fos activation in response to
      intraventricular leptin (3.5 microg), intragastric Ensure (10 ml over 10 min), or
      their combination. Leptin alone did not affect Ensure intake but significantly
      increased the suppression of intake produced by the intragastric preload. Within
      the nucleus of the solitary tract (NTS), leptin alone did not stimulate c-Fos but
      significantly elevated the number of c-Fos positive cells in response to
      intragastric Ensure at medial and rostral levels. Within the paraventricular
      nucleus (PVN), both leptin and the gastric load stimulated c-Fos expression, but
      the combination resulted in significantly greater number of c-Fos positive cells.
      These data demonstrate that leptin modulates the feeding inhibition produced by
      meal-related signals and suggest that this modulation occurs at the levels of the
      NTS and PVN.

PMID- 11239990
TI  - Do Norway rats (Rattus norvegicus) synchronize their estrous cycles?
AB  - Estrous synchrony was tested using 10 pairs of sibling female rats (Rattus
      norvegicus). A Monte Carlo bootstrap simulation was used to construct random
      control groups to avoid previous statistical errors and to test for significance
      when there are irregular cycles. The 10 pairs of females did not exhibit estrous
      synchrony. The effect of cycle irregularity on the limits of synchrony was
      analyzed using an equation that the related degree of cycle regularity to the
      degree of synchrony. This equation significantly predicted the limits of
      synchrony: cycle irregularity limits both the maximum and minimum degree of
      synchrony that can occur between two females. Finally, simulations of the
      expected levels of synchrony in groups of five rats were compared to the original
      study on estrous synchrony. The simulations indicated that the results of the
      original study were consistent with chance levels of synchrony. It is concluded
      that there is no evidence that Norway rats synchronize their estrous cycles.
      Evolutionary implications are discussed.

PMID- 11239991
TI  - Catecholamine levels in practitioners of the transcendental meditation technique.
AB  - With the aim of evaluating the sympathetic-adrenal medulla system in subjects
      practicing transcendental meditation (TM), their plasma catecholamine levels were
      determined at two different times of day. The study group consisted of 19
      subjects who regularly practice either TM or Sidhi-TM technique, with a control
      group made up of 16 healthy subjects who had not previously used any relaxation
      technique. Catecholamine plasma levels were determined by high performance liquid
      chromatography, at 0900 and 2000 h. Morning and evening norepinephrine (NE)
      levels and morning epinephrine (E) levels were significantly lower in the TM
      group than in the control subjects (morning NE levels, pg/ml, mean+/-S.E.: TM
      group 136.6+/-13.0, control 236.8+/-21.0, P=.0001; evening NE levels: TM group
      119.7+/-10.8, control 175.6+/-17.4, P=.009; morning E levels, pg/ml: TM group
      140.2+/-10.6, control 196.7+/-23.8, P=.019). No differences were recorded for
      evening E levels and dopamine (DA) levels. No significant differences were found
      for catecholamine levels measured at different times of day in the TM group,
      demonstrating a lack of daily hormonal rhythm. Anxiety levels were similar in
      both groups. Based on the results obtained, it can be considered that the regular
      practice of TM has a significant effect on the sympathetic-adrenal medulla
      system. A low hormonal response to daily stress caused by sympathetic tone
      regulation through regular TM could explain our results, as well as the
      physiological and other effects related to the field of health described in those
      who practice meditation.

PMID- 11239992
TI  - Metabolic and behavioral responses in pre-weanling rats following alteration of
      maternal diet.
AB  - In rat pups, blockade of fatty acid oxidation by administration of 2
      mercaptoacetate (MA) produces an increase in independent ingestion by 12 days of
      age. In contrast, administration of methyl palmoxirate (MP) fails to increase
      intake or to alter oxidation of fatty acids in young rats due to the high
      proportion of medium chain triglycerides (MCT) in rat milk. In the present
      experiments, the composition of rat milk was altered by placing dams on a high
      fat (HF) diet to examine the development of ingestive responding in rat pups
      following administration of MP. Following delivery of MP (0.5--10 mg/kg), pups
      were placed in a cage inside an incubator for 1, 3, or 6 h, and then received an
      intake test consuming a commercial half-and-half milk diet from the floor of test
      containers. Blood was collected from additional groups of pups for measurement of
      beta-hydroxybutyrate (beta HBA) and glucose levels. The results demonstrated that
      administration of MP produced significant reductions in beta HBA levels after 3 h
      in 12- and 15-day-old pups, but behavioral responses were noted only in pups aged
      15 days. Similar results were obtained following administration of MA to pups
      reared by dams on HF diets; physiological responses were observed at 12 and 15
      days of age, but behavioral responses were not observed after administration of
      MA until 15 days of age. Taken together, these results suggest that (1) changes
      in fatty acid oxidation may represent an early metabolic signal that can
      influence intake in rat pups and (2) alteration of the dam's diet produces
      physiological and behavioral changes in the pups.

PMID- 11239993
TI  - Olfactory discrimination conditioning in the moth Spodoptera littoralis.
AB  - We used a proboscis extension reflex (PER) to study the olfactory discrimination
      capability in the moth Spodoptera littoralis. Already after a single experience,
      moths were capable to discriminate a rewarded from an unrewarded odor. In the
      first experiment, when rewarded and unrewarded odors were substituted for each
      other, moths were able to undergo reversal conditioning already after two
      experiences. Both shorter and longer inter-trial intervals (ITIs) supported high
      degrees of learning. In a second experiment, moths could solve both feature
      positive and -negative discrimination tasks. Two hypotheses for the way in which
      these associations exert their discrimination performance are considered. The
      moth's olfactory physiology has been extensively studied. This animal thus
      provides a powerful system in which to study the neurobiology of olfactory
      discrimination and odor recognition.

PMID- 11239994
TI  - Tickling induces reward in adolescent rats.
AB  - In adolescent rats, 50-kHz vocalizations are most evident during tickling and
      rough-and-tumble play. The following experiments evaluated whether 50-kHz
      vocalizations reflect positive social affect by determining (1) if tickling is a
      rewarding event, (2) if social or isolate housing conditions differentially
      influence the response (since housing condition has been found to effect the
      reward magnitude of social encounters), and (3) if drugs that work on mu-opiate
      receptors, which has been hypothesized to control positive social affect,
      modulate tickling. Tickling was positively reinforcing as demonstrated by
      elevated operant behavior, conditioned place preference, and approach measures. A
      significant negative correlation between vocalization rate and approach latency
      measures was found. Social housing reduced tickle-induced vocalizations and
      approach speeds compared to isolate housing. Naloxone (1 mg/kg) increased
      vocalization in the socially housed rats and decreased it in isolated Subjects
      (Ss). These findings suggest that tickling can be used to induce positive social
      affect in rodents, and that it is modulated by endogenous opioids.

PMID- 11239995
TI  - Centrally injected atropine reduces hyperglycemia caused by 2-DG or
      immobilization stress in awake rats.
AB  - The physiological significance of central cholinergic neurons was investigated by
      verifying the effect of previous intracerebroventricular administration of
      atropine on the hyperglycemia induced by 2-deoxyglucose (2-DG) or by
      immobilization stress in unrestrained, nonanesthetized rats. Intravenous 2-DG
      induced a marked increase in plasma glucose that was not affected by atropine
      injected intracerebroventricularly 30 min before. However, the hyperglycemia
      induced by intracerebroventricular 2-DG was significantly reduced by previous
      intracerebroventricular injection of atropine. Immobilization induced a rapid
      increase of plasma glucose levels that was reduced by about 50% by
      intracerebroventricular injection of atropine. The increase in plasma lactate
      induced by intravenous 2-DG, or immobilization, was not significantly affected by
      previous intracerebroventricular injection of atropine. The data suggest that
      central cholinergic neurons participate in the complex neural events responsible
      for the hyperglycemic response to neurocytoglucopenia and to stressful
      situations.

PMID- 11239996
TI  - Altered responsiveness to stress and NMDA following prenatal exposure to cocaine.
AB  - Pregnant Sprague--Dawley rats were treated once daily with 40-mg/kg cocaine or
      saline from gestation days (GD) 12 to 21. A third group of pregnant dams was used
      as a pairfed control. Male and female offspring were examined for stress
      endurance response as determined by the cold-water swim test on postnatal days
      (PND) 21, 30, 40, and 60. Male and female offspring exposed to cocaine in utero
      were found to have diminished tolerance and altered hormonal response to stress.
      Moreover, prenatal cocaine exposure has been associated with significant
      increases in severity of N-methyl-D-aspartate (NMDA; 35 mg/kg) behavioral
      responses (tail twitches, wetdog shaking, and convulsion) as compared to control.
      Examining the experimental groups for pain sensitivity using the tail-flick and
      the hot-plate methods indicated that prenatal cocaine exposure altered pain
      sensitivity. NMDA receptor binding studies showed an increase in receptor density
      in the hippocampus and hypothalamus of the cocaine-treated group. These results
      indicate that gestational cocaine exposure is associated with long-term
      alterations in response to stress, NMDA receptor, and pain sensitivity in the rat
      offspring.

PMID- 11239997
TI  - A behavioral characterization of the effects of food deprivation on food and
      nonfood object interaction: an investigation of the information-gathering
      functions of exploratory behavior.
AB  - Previous research has shown that exploratory behavior serves not only to procure
      food, but also as a means of general information gathering. The purpose of this
      experiment was to investigate the function of exploratory behavior in rats by
      measuring behavior as they interacted with food and nonfood stimuli under
      different levels of food deprivation. Rats were food-deprived (0, 24, and 48 h),
      given free access to an open-field arena, and videotaped for a 20-min test
      session. The rats' behavior was assessed in a manner that isolated locomotor-,
      object-, and nonobject-related components. Deprivation did not affect locomotor
      activity levels; however, a decrease in rearing and propping against the test
      arena was shown. Rats distinguished between the food and nonfood objects because
      they attempted to ingest the food but not the nonfood object. Deprivation did
      result in increased contact with food objects; however, nonfood object
      interactions were maintained throughout the test session. These results suggest
      that exploratory behavior is separable from food seeking and functions in
      acquisition of information relating to multiple aspects of the environment.

PMID- 11239998
TI  - Hypertonic glucose preloads act preabsorptively to decrease intake in rats on
      postnatal day 18.
AB  - To determine if preloads of glucose act preabsorptively or postabsorptively to
      inhibit intake, 18-day-old rat pups were deprived for 24 h and then provided with
      sweet milk during a 30-min independent ingestion test. Five minutes before the
      test, gastric preloads (5% body weight, BW) or intraperitoneal injections (4
      ml/kg BW) of isotonic, hypotonic, and hypertonic solutions of glucose or 2-deoxy
      D-glucose (2-DG) were administered. There were two major results: First, preloads
      of 20% glucose decreased intake much more than intraperitoneal injections of 20%
      glucose. Second, a preload of 20% 2-DG, which decreases, rather than increases
      glucose utilization, was as effective as a preload of 20% glucose in decreasing
      intake. These results are consistent with a preabsorptive osmotic mechanism, but
      not with a postabsorptive metabolic mechanism, for mediating most, if not all, of
      the inhibition of intake 5 min after preloads of 20% glucose in rats on postnatal
      day 18 (P18).

PMID- 11239999
TI  - Adaptation to capsaicin burn: effects of concentration and individual
      differences.
AB  - Human subjects rated the time course of the burn produced by three concentrations
      of capsaicin applied to the tongue via filter papers. Data were fit to a dynamic
      model composed of a level detector, a change detector, and a double integrator.
      These three processes responded differently to concentration. 6-n-Propyl-2
      thiouracil (PROP) taster status correlated positively with the integrator
      process. Although a minority of subjects showed evidence of the integrator
      process, any subject with an integrator process at a given concentration also
      showed it at any higher concentration.

PMID- 11240001
TI  - Food-anticipatory activity persists after olfactory bulb ablation in the rat.
AB  - Restricted daily food access acts as an entraining stimulus (zeitgeber) for a
      circadian clock, the feeding-entrainable oscillator (FEO). There are many
      properties of a daily meal that could potentially convey timing information to
      the FEO. Olfactory cues associated with feeding are one such property. In order
      to rule out olfaction as a necessary entraining stimulus, olfactory bulbectomized
      and sham-operated male Sprague--Dawley rats had access to food for 2 h each day.
      Food bin approach behavior was monitored as an index of food-anticipatory
      activity (FAA). Both groups entrained to the daily meal with an increase in
      feeder approach time several hours before meal onset. There were no significant
      differences in the timing or the amount of FAA between groups. Furthermore, FAA
      was maintained during 3 days of food deprivation in both groups. In accordance
      with previous studies, the results show that olfactory cues are not necessary for
      the entrainment of FAA.

PMID- 11240000
TI  - Ethanol perception and ingestion.
AB  - Ethanol is a common dietary constituent, but knowledge of its chemosensory
      properties and their relationship to its ingestion is limited. Twenty-five male
      and 25 female, light-regular ethanol consumers participated in five test
      sessions. Sessions involved determination of taste, olfactory and nasal
      irritation thresholds for ethanol, taste thresholds for tetralone, suprathreshold
      intensity and quality judgements, determination of phenylthiocarbamide (PTC)
      taster status, acute oral exposure effect of ethanol on ratings for sucrose,
      NaCl, citric acid and quinine hydrochloride and hedonic judgments of beers.
      Questionnaires on personality traits, diet and health were also completed and
      body composition determined. Diet histories were obtained on three random days. A
      randomized subset of sensory tests and questionnaires were administered each
      session. The rank order of ethanol thresholds was taste>nasal irritancy>olfaction
      and the predominant taste near threshold was bitter. Except for a lower taste
      threshold in females, no other effects of gender, PTC taster status, ethanol use
      or body composition were observed. Acute exposure to ethanol suppressed the
      bitterness of quinine, but enhanced its bitter aftertaste. Ethanol use was not
      associated with differences in dietary, sensory or textural characteristics.
      Thus, among light to regular ethanol consumers, no substantive association was
      observed between sensory responses to ethanol and diet.

PMID- 11240002
TI  - Individual differences in rat locomotor activity are diminished by nicotine
      through stimulation of central nicotinic acetylcholine receptors.
AB  - An increasing body of research has focused on isolating factors that predict or
      alter individual differences in the behavioral and neural processes mediating the
      effects of abused drugs. Within this framework, the current report assessed
      individual differences and the locomotor effect of nicotine. Rats were screened
      for activity induced by a novel environment. Rats, which were more active to
      initial environment exposure, remained more active even after seven additional 30
      min exposures to the same environment. Treatment with nicotine-di-D tartrate (1
      mg/kg, sc) disrupted this effect. This nicotine disruption of individual
      differences occurred whether nicotine suppressed locomotor activity (initial
      administration) or stimulated locomotor activity (seventh and eighth
      administration). Mecamylamine (1 mg/kg), but not hexamethonium (10 mg/kg),
      completely blocked the suppressant and stimulant effects of nicotine. Further,
      mecamylamine restored the nicotine-induced disruption of individual differences;
      hexamethonium had no effect. This data pattern suggests that the disruptive
      effects of acute and chronic nicotine on individual differences were mediated by
      neural nicotinic acetylcholine (nACh) receptors.

PMID- 11240004
TI  - Novelty seeking in periadolescent mice: sex differences and influence of
      intrauterine position.
AB  - In rodents, beside basic sex differences, a certain degree of within-gender
      phenotypic variation can also be provided in utero by hormones from adjacent
      fetuses. We investigated novelty-seeking behavior in two groups of male and
      female mice from know intrauterine position: 2M (between males) and 0M (between
      females). Subjects were assessed during periadolescence (postnatal days 33--43),
      an ontogenetic phase, which is characterized by an elevated expression of this
      novelty-seeking behavior. Periadolescent mice underwent a familiarization session
      for 3 consecutive training days with one side of a two-chamber apparatus. On
      testing day 4, the opening of a partition, which allowed mice to freely move from
      the familiar compartment to a novel one, produced an increased behavioral arousal
      in all animals. Marked sex differences were found, with females being in general
      more active than males, whereas the latter showed significantly higher levels of
      novelty seeking than females. Uterine position failed to affect the profile of
      novelty preference in females, whereas within the male group 2M subjects
      expressed a marked profile of novelty seeking. The differential titers of sex
      hormones reported to characterize the 0M and 2M condition early in fetal
      development are suggested to account for the individual variability in the
      seeking for novelty within the male group during puberty.

PMID- 11240003
TI  - Sexual and aggressive interactions in a visible burrow system with provisioned
      burrows.
AB  - The visible burrow system (VBS) is a habitat providing burrows and an open area
      for mixed-set rat colonies. Provisioning of food and water in the burrows makes
      it unnecessary for potentially defensive animals to leave the burrows to
      eat/drink on the surface, and enables evaluation of new types of agonistic
      interactions that may emerge when this necessity is removed. In such colonies,
      subordinate males showed high magnitude tunnel guarding behavior, occupying a
      tunnel opening onto the surface and confronting the dominant. Dominants, in
      response, made lunges into the tunnels, but quickly retreated without gaining
      entry, apparently stopped by contact with the defender's vibrissae. Dominants
      also made and continued to make lateral attacks to the wall adjacent to the
      tunnels guarded by subordinates, although these were useless in terms of
      affording contact with the subordinate. Dominant-female agonistic interactions
      were more frequent than those of dominants and subordinates. These were largely
      initiated by the male, and involved female defensive behavior. Nonetheless,
      females, unlike subordinates, failed to show tunnel guarding and continued to
      utilize the surface freely. They also spent more time in the vicinity of the
      dominant over days of colony formation. This apparent paradox may reflect that
      females were seldom wounded, and that the initial site of male contact with
      females was the female's anogenital area, findings suggesting that interactions
      of males and females often reflect male sexual advances, countered by female
      defenses that effectively protect nonestrus females from mounting and copulation.

PMID- 11240005
TI  - Neuroendocrine consequences of very early weaning in swine.
AB  - An experiment was conducted to investigate the consequences of very early weaning
      of piglets on neuroendocrine variables and growth. Sixty piglets from eight
      litters were either weaned on Postnatal Day 6 (early weaning, or EW piglets) or
      left with their dam until normal weaning at Day 28 (control piglets, or C). At
      Days 5, 7, 11, 14, and 19, urine was collected between 7:00 and 8:00 a.m. for the
      measurement of catecholamines, glucocorticoids, and creatinine. Compared with C,
      EW piglets displayed a transient increase in urinary cortisol on the day
      following separation from their dam (Day 7) (P<.05). Urinary norepinephrine (NE)
      was three times lower in EW compared to C piglets from Day 7 until Day 14 (P<.01)
      but there was no difference between the two groups on Day 19. Urinary epinephrine
      (EPI) did not differ between C and EW piglets on the day after weaning.
      Thereafter, EW piglets displayed a three times drop in urinary EPI as compared to
      C piglets until the end of the period (P<.01). Weaning induced an immediate
      reduction in food intake and growth rate and at Day 28, the body weight of EW
      piglets was 1.60 kg lower than that of C piglets (P<.0001). In conclusion,
      weaning of 6-day-old piglets results in a marked and prolonged suppression of the
      release of catecholamines. This result likely reflects physiological responses to
      insufficient energy intake after weaning, as reflected also by changes in
      thermoregulatory behavior. The transient increase in cortisol excretion in
      weanlings may be caused by both emotional distress and acute food deprivation.

PMID- 11240006
TI  - Strain and gender differences in the behavior of mouse lines commonly used in
      transgenic studies.
AB  - The present study was aimed at establishing behavioral differences between three
      inbred mouse strains (129S2/SvHsd, C57BL/6JOlaHsd, FVB/NHsd) and two F1 hybrid
      lines derived from them (129 x C57BL/6 and 129 x FVB). The choice of the given
      strains was based on the frequent use of these mice in transgenic research. For
      the behavioral phenotyping, we employed a test battery consisting of the
      following models: elevated plus-maze (EPM), open field (OF), light-dark
      exploration, spontaneous locomotor activity, rota-rod (RR), Porsolt's forced
      swimming test (FST), and Morris water task. Significant variations between the
      strains were established in all tests. Anxiety-like behavior was more pronounced
      in the 129S2/Sv and 129 x C57BL/6 mice, the FVB/N mice were spontaneously
      hyperactive, the best coordination ability was demonstrated by the C57BL/6 and
      129 x C57BL/6 groups. A good performance in the learning test was established in
      both hybrid lines and the 129S2/Sv mice, whereas the well-known visual impairment
      of the FVB strain was confirmed by low performance in spatial and non-spatial
      tasks. Differences related to the gender were revealed occasionally; most
      importantly, 129 x C57BL/6 males had a higher anxiety level than their female
      counterparts in the EPM. Several other gender dissociations suggest the strain
      and task specificity. In conclusion, we would like to highlight the importance of
      the genetic background and gender of mice for the molecular biological and
      pharmacological studies and also the need for well-established testing protocols
      to obtain wide information at the first stage of behavioral screening of
      genetically modified mice.

PMID- 11240007
TI  - Near-field visual acuity in Japanese jungle crows (Corvus macrorhynchos).
AB  - The near-field visual acuity of three Japanese jungle crows (Corvus
      macrorhynchos) was determined by means of operant conditioning. The task was
      discrimination of grating stimuli, and the threshold was measured by up-and-down
      method between sessions. To keep observing distance constant, a photo sensor was
      used and the head position was behaviorally fixed. The average visual acuity was
      8.4 cycles/degree. When compared with other birds, this result is better than
      that of pigeons, and worse than that of predators.

PMID- 11240008
TI  - Relationships between feeding and locomotion behaviors after central
      administration of CRF in chicks.
AB  - The effect of intracerebroventricular injection of corticotropin-releasing factor
      (CRF) on various behaviors in chicks was determined at 15-min intervals over a 30
      min period. Food intake of chicks was significantly decreased, and pecking rhythm
      was significantly delayed by CRF during the first 15-min post-injection. The
      similar tendencies were observed in the second 15-min post-injection, but not
      significantly different. Stepping, as an indicator of locomotion, was not
      different at 15-min post-injection, but was increased by CRF, thereafter. These
      results suggest that CRF acts within the central nervous system to decrease food
      intake and increase locomotion in the chick.

PMID- 11240009
TI  - Vaccination with autologous dendritic cells: from experimental autoimmune
      encephalomyelitis to multiple sclerosis.
AB  - Autoimmune diseases such as multiple sclerosis (MS) are characterized by the loss
      of tolerance to self-determinants, activation of autoreactive lymphocytes and
      subsequent damage to single or multiple organs. The mechanisms by which
      autoimmune responses are triggered, and how activation of autoreactive
      lymphocytes is initiated and maintained, are not fully understood. Therapeutic
      approaches in autoimmune diseases have so far concentrated on antigens and T
      cells. Given the exceptional capacity of dendritic cells (DCs) to induce immunity
      in vivo, recent reports of the first successful clinical trials based on
      vaccination of tumor patients with autologous blood DCs pulsed in vitro with
      tumor antigen come as no surprise. The recent identification of tolerogenic
      subsets of DCs and their generation in culture may allow a novel approach to
      induce tolerance in autoimmune diseases. By selective in vitro manipulation of
      DCs and their subsequent reinfusion, DC-mediated tolerance has been achieved in
      animal models of human autoimmune diseases, including experimental autoimmune
      encephalomyelitis in Lewis rats and SJL/J mice and spontaneous diabetes in NOD
      mice. In vitro observations of human blood DCs are promising for DC-based
      treatment of MS and other diseases with an autoimmune component. Data from animal
      models and human materials suggest that DC-based immunotherapy could be
      beneficial at least as a complement to conventional therapy. Molecular-biological
      approaches to tolerogenic DCs could provide a rationale for designing
      immunotherapeutic strategies in autoimmune diseases.

PMID- 11240010
TI  - Expression and function of inducible nitric oxide synthase in neurons.
AB  - Enzymatically derived nitric oxide (NO) has been implicated in numerous
      physiological and pathological processes in the brain. Whereas during development
      NO participates in developmental and maturation processes, excess NO production
      in the adult in response to inflammation, injury, or trauma participates in both
      cell death and repair. The expression and activity of the inducible isoform of NO
      synthase (iNOS) play a pivotal role in sustained and elevated NO release. Recent
      evidence suggests that neurons can respond to proinflammatory stimuli and take
      part in brain inflammation. Neuronal iNOS expression has been described in
      different experimental settings, including cytokine stimulation of neuronal cell
      lines and primary neurons in vitro as well as in animal models of stroke and
      neurodegeneration. This article outlines different conditions leading to iNOS
      gene transcription and expression in neurons and neuronal cells and highlights
      the potential impact on human brain inflammation and neurodegeneration.

PMID- 11240012
TI  - EMAP cytokine expression in developing retinas of normal and retinal degeneration
      (rd) mutant mice.
AB  - Endothelial-monocyte-activating polypeptide (EMAP) is a proinflammatory cytokine
      and a mediator of programmed endothelial cell death. To gain insight into its
      possible functions during retinal development and degeneration, the cellular
      distribution of EMAP protein was compared in control and retinal degeneration
      (rd) mice. EMAP immunoreactivity was confined to the ganglion cell layer (GCL)
      and the inner nuclear layer (INL). There were significant differences in the
      intensity of EMAP labeling in the GCL and the INL when comparing control and rd
      mouse retinas. Rd retinas contain much more EMAP immunoreactivity in the GCL and
      the INL than the control retinas at postnatal day 14, which is the time point
      immediately after the onset of the degeneration of the rd retina. Histopathologic
      examination showed no significant abnormalities in the GCL and INL in the rd
      mouse, despite a great degree of photoreceptor cell death from P12 to P18. Light
      and electron microscopic studies immunolocalize EMAP protein to the cytoplasm of
      retinal ganglion cells, amacrine cells, and horizontal cells. The data suggests
      that EMAP is synthesized and accumulated as an intracellular precursor protein
      that has a functional role in translation and protein synthesis as a cofactor for
      tRNA synthetase. The increased expression of EMAP precursor levels in rd mouse
      retina may reflect the enhanced rate of translation and protein synthesis in the
      production of endogenous factors that promote survival in the GCL and INL.

PMID- 11240011
TI  - Chemical sympathectomy increases the innate immune response and decreases the
      specific immune response in the spleen to infection with Listeria monocytogenes.
AB  - Many investigators have shown that ablation of the sympathetic nervous system
      (SNS) with 6-hydroxydopamine (6-OHDA) can alter cell-mediated and humoral immune
      responses to antigenic challenge. Fewer studies have examined 6-OHDA-induced
      changes in natural immunity. In this study, we have examined the effect of
      chemical sympathectomy on the nonspecific and specific phases of the response to
      infection with Listeria monocytogenes. Sympathectomy decreased splenic bacterial
      loads 3 and 5 days post-infection and increased splenic neutrophils 3 days post
      infection. Sympathectomy decreased splenocyte numbers and antigen-stimulated
      cytokine secretion from splenocytes. These results suggest that the SNS
      influences specific responses by modulating innate responses.

PMID- 11240013
TI  - An experimental model of stress-induced immunosuppression produced by electrical
      stimulation of the brain in the rat.
AB  - The present paper reports a model of stress induction, based on electrical
      stimulation of the brain in normal Wistar rats. Stress-related stimulation of the
      hypothalamic-pituitary-adrenal axis produced a rise in circulating corticosterone
      levels that correlated significantly with the impairment of some immunological
      parameters, such as delayed hypersensitivity reactions to dinitrofluorobenzene
      and to sheep red blood cells, together with changes in splenocyte proliferation
      and phagocytic activity of peritoneal macrophages. This experimentally elicited
      stress in the rat is proposed as a suitable model of immunosuppression that could
      be used for the evaluation of drugs with potential immunomodulatory properties.

PMID- 11240014
TI  - STAT expression and localization in the central nervous system during autoimmune
      encephalomyelitis in Lewis rats.
AB  - Autoimmune inflammation in the central nervous system (CNS) is maintained by
      secretion of a large number of cytokines. To elucidate its molecular mechanisms,
      we examined the expression and localization of STAT1, STAT3, STAT4 and STAT6
      molecules, which are the downstream molecules of the cytokine signal transduction
      pathway, in the CNS during acute experimental autoimmune encephalomyelitis (EAE)
      induced in Lewis rats. Western blot analysis demonstrated that STAT1 protein
      increased gradually till the recovery stage, whereas STAT4 protein showed abrupt
      increase at the early stage followed by gradual decrease. STAT3 and STAT6 showed
      stable expression throughout the course of the disease. The kinetics of the
      phosphorylated form of STAT1 and STAT4 roughly paralleled that of the total
      protein although the peak of STAT3 phosphorylation was recognized at the
      preclinical stage. Immunohistochemical examinations revealed that STAT3 and
      STAT4, but not STAT1 and STAT6, immunoreactivities were mainly expressed in
      astrocytes and microglia, respectively, and were closely associated with
      inflammatory lesions. Taken together, these findings suggest that STAT3 and STAT4
      play an important role in the formation of, and recovery from, autoimmune
      inflammation in the CNS.

PMID- 11240015
TI  - Axonal transport of TNF-alpha in painful neuropathy: distribution of ligand
      tracer and TNF receptors.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a key player in peripheral nerve
      injury. In the inflammatory chronic constriction injury (CCI) model of sciatic
      neuropathy, upregulation of TNF-alpha mRNA and protein at the site of nerve
      injury has been associated with pain. We now report the distribution of
      endogenous TNF-alpha protein and its receptors along normal and CCI-injured
      sciatic nerves, and within the corresponding lumbar dorsal root ganglia (DRG).
      Using Western blotting, TNF-alpha was found to be distinctly increased at the
      injury site, as well as in the axons just distal to the corresponding DRG. The
      TNF-alpha signal between the injury site and DRG (midaxonal) was induced between
      2 and 5 days post-CCI, suggesting activation of TNF-alpha axonal transport.
      Endogenous TNF-alpha was localized in small-diameter, presumably nociceptive, and
      large-diameter, presumably mechanoceptive, DRG sensory neurons in both normal and
      CCI animals. Intraneural microinjection of biotin-labeled TNF-alpha showed
      specific axonal uptake at the injection site, as detected by avidin-biotin
      peroxidase histochemistry, and confirmed by co-localization with neurobiotin
      tracer. In control animals, fast retrograde transport of biotinylated TNF-alpha
      to both L4 and L5 DRG neurons was apparent 6 h following injection. TNF receptors
      TNFRI and TNFRII co-localized with biotinylated TNF-alpha tracer along the nerve
      trunk, suggesting that TNF-alpha transport may be receptor-mediated. In animals
      with CCI neuropathy, uptake of biotinylated TNF-alpha by neuronal soma was
      inhibited. Instead, there was signal accumulation in the axons immediately distal
      to the DRG, and TNFRI and RII were increased at this same anatomic location.
      These findings highlight a dynamic process of TNF-alpha protein and receptor
      regulation throughout the peripheral neural axis that bears on both the normal
      function of DRG neurons and the pathogenesis of painful neuropathies.

PMID- 11240017
TI  - Inhibition of CD40 signaling pathway by tyrphostin A1 reduces secretion of IL-12
      in macrophage, Th1 cell development and experimental allergic encephalomyelitis
      in SJL/J mice.
AB  - Activation of antigen presenting cells through the interaction of CD40 with its
      ligand is a critical co-stimulatory signal for IL-12 production and Th1
      differentiation. Tyrphostins are organic molecules that inhibit the
      phosphorylation of protein tyrosine kinases. We show that tyrphostin A1 inhibits
      CD40L-stimulated IL-12 production in macrophage cultures and antigen-induced
      generation of Th1 cells. Our data also show that tyrphostin A1 blocks CD40L
      induced translocation of NF-kappaB to the nucleus, and reduces the activation of
      IL-12 p40 gene. In vivo therapy with A1 leads to decrease in generation of myelin
      basic protein (MBP) specific encephalitogenic T cells. In addition, treatment of
      SJL/J mice with A1 results in attenuation of experimental allergic
      encephalomyelitis (EAE).

PMID- 11240016
TI  - Reduction in glial immunity and neuropathology by a PAF antagonist and an MMP and
      TNFalpha inhibitor in SCID mice with HIV-1 encephalitis.
AB  - The effects of anti-inflammatory drugs on glial immunity and neuropathology were
      determined in a severe combined immune deficiency (SCID) mouse model of HIV-1
      encephalitis. HIV-1-infected human monocyte-derived macrophages (MDM) are
      stereotactically inoculated into basal ganglia resulting in a multinucleated
      giant cell encephalitis. A platelet activating factor antagonist and a matrix
      metalloproteinase inhibitor, which also inhibits tumor necrosis factor alpha
      release, were administered to animals at the time of the MDM inoculation. The
      drugs administered in combination markedly reduced brain inflammation,
      astrogliosis and microglia activation. These findings demonstrate that reduction
      of brain inflammatory responses, independent of viral replication, can affect
      HIVE pathology in an animal model system of disease.

PMID- 11240018
TI  - Behavioral characterization of a mouse model of premature immunosenescence.
AB  - In previous studies we have shown that differences in life span among members of
      Swiss mouse populations appear to be related to their performance in a T-maze,
      with a slow performance ("slow" mice) being linked to an impaired immune function
      and a shorter life span when compared to "fast" mice, which led us to propose the
      slow mice as a model of immunosenescence. In the present study we demonstrate
      that in a tightrope test of neuromuscular vigor and coordination the slow mice
      show a worse performance, needing more time to complete the task. Moreover, these
      animals show a decreased locomotor activity and an increased level of
      emotionality/anxiety in three standard behavioral tests (the holeboard, the open
      field and the plus-maze) when compared to fast mice. All these behavioral
      features were most marked in the slow females. The results also indicate that
      slow animals show a decreased chemotaxis of macrophages and lymphocytes, as well
      as a reduced lymphoproliferative response to mitogens. The data supports our
      claim that slow or hyperemotional mice, in which immune and neurobehavioural
      functions appear to be impaired, may be a useful model of premature aging.

PMID- 11240019
TI  - Characterization of T cells that are activated after depletion of major
      encephalitogenic T cells in rat autoimmune encephalomyelitis.
AB  - In rat experimental autoimmune encephalomyelitis (EAE), encephalitogenic T cells
      mainly use Vbeta8.2 of TCR, but it is not clear whether Vbeta8.2 is the sole
      encephalitogenic TCR. To address this issue, we examined the immunological status
      of Lewis rats that had been treated with anti-Vbeta8.2 mAb and immunized with
      myelin basic protein (MBP). It was demonstrated that rats in which the majority
      of Vbeta8.2+ T cells had been depleted developed clinical EAE and possessed newly
      expanded Vbeta10. Analysis of T cell lines established from these animals
      revealed that T line cells responded to a minor epitope in the MBP molecule.
      However, treatment with a mixture of anti-Vbeta8.2 and anti-Vbeta10 mAbs reduced
      the clinical severity of EAE but did not induce complete suppression of the
      disease due to new activation of Vbeta6. These findings suggest that rapid and
      frequent examination of the TCR repertoire is essential to identify pathogenic
      TCRs and to establish TCR-based immunotherapy for autoimmune diseases.

PMID- 11240020
TI  - P0 glycoprotein peptides 56-71 and 180-199 dose-dependently induce acute and
      chronic experimental autoimmune neuritis in Lewis rats associated with epitope
      spreading.
AB  - Two synthetic peripheral nerve myelin P0 protein peptides, an immunodominant
      (amino acids 180-199) and a cryptic (amino acids 56-71) one, induced an acute or
      chronic course of experimental autoimmune neuritis (EAN) in Lewis rats, when
      given at low dose (50-100 microg/rat) or high dose (250 microg/rat),
      respectively. Corresponding to the different clinical course, pathological
      changes and immune responses were found: (1) Onset of clinical signs of P0
      peptide 56-71 (P0 56-71) induced EAN was 1-3 days later than in P0 peptide 180
      199 (P0 180-199) induced EAN at all immunizing doses, whereas the peak of the
      disease occurred at a similar time point post immunization (p.i.), i.e. at days
      14-16 p.i. in P0 56-71 induced EAN and at day 16 p.i. in P0 180-199 induced EAN.
      (2) Intramolecular epitope spreading as assessed by delayed type hypersensitivity
      response occurred in P0 56-71 induced EAN at both low and high antigen doses and
      in P0 180-199 induced EAN at high antigen dose (250 microg/rat) only. (3) P0 180
      199 stimulated higher levels of interferon-gamma production in P0 180-199 induced
      EAN than in P0 56-71 induced EAN and vice versa. (4) Histopathologic evaluation
      revealed a similar grade of mononuclear cell infiltration in the sciatic nerves
      of both types of EAN, but more severe demyelination was found in P0 180-199
      induced EAN compared to P0 56-71 induced EAN. The results support the hypothesis
      that high dose autoantigen immunization induces extensive determinant spreading
      and chronic course of autoimmune diseases.

PMID- 11240021
TI  - Apolipoprotein E modulates glial activation and the endogenous central nervous
      system inflammatory response.
AB  - Apolipoprotein E (apoE) is a 299 amino acid protein that is associated with risk
      of developing Alzheimer's Disease (AD) and outcome after acute brain injury. To
      investigate the possibility that apoE modulates glial activation we studied the
      effect of endogenous apoE on inflammatory gene regulation in vitro and in vivo.
      Our results indicate that apoE downregulates CNS production of TNFalpha, Il
      1beta, and Il-6 mRNA following stimulation with lipopolysaccharide (LPS). This
      effect of endogenous apoE on inflammatory gene regulation appears to be specific,
      and may account for the biological role that apoE plays in acute and chronic
      human neurological disease.

PMID- 11240022
TI  - CD28-B7 costimulation: a critical role for initiation and development of
      experimental autoimmune neuritis in C57BL/6 mice.
AB  - CD28 provides a critical costimulatory signal for antigen-specific T cell
      activation. Because CD28 is an important factor in the development of autoimmune
      diseases, we investigated its role in T cell-mediated experimental autoimmune
      neuritis (EAN), an animal model of Guillain-Barre syndrome in humans. CD28
      deficient mutant (CD28-/-) C57BL/6 mice and corresponding wild-type mice were
      immunized with P0 peptide 180-199, a purified component of peripheral nerve
      myelin, and Freund's complete adjuvant. As a result, all wild-type mice developed
      severe EAN, in contrast, none of the CD28-/- mice manifested clinical signs of
      disease. Additionally, CD28-/- mice had fewer IL-12 producing cells in sciatic
      nerve sections and fewer IFN-gamma secreting splenic cells than wild-type mice on
      day 24 post immunization, i.e., at the peak of clinical EAN. At that time point,
      CD28-/- mice had milder infiltration of such inflammatory cells as macrophages,
      CD4+ T cells and monocytes into sciatic nerve tissues and less demyelination than
      wild-type mice. Moreover, the CD28-deficiency led to reduced production of
      specific anti-P0 peptide 180-199 antibodies compared with wild-type mice.
      Evidently, CD28 is required for interaction with B7 to regulate the activation of
      T and B cells that initiates development of EAN.

PMID- 11240023
TI  - Long-term colony housing in Long Evans rats: immunological, hormonal, and
      behavioral consequences.
AB  - The distribution pattern and the function of blood immune cells were investigated
      for 10 weeks in three mixed-sex colonies of Long Evans rats. After colony
      formation, a despotic dominance system was established between the males. This
      paper focuses on differences between subdominant colony and pair-housed control
      males. A reduced body mass development and hormonal status in subdominant males
      indicate stressful colony conditions. Subdominant males had lower numbers of CD4
      and CD8 T cells, pronounced granulocytosis and reduced lymphocyte proliferation
      rates as compared with controls. The persistency of changes in subdominant males
      offers the opportunity to investigate the effects of long-term immuno-modulation
      on health.

PMID- 11240024
TI  - Expression of authentic substance P receptors in murine and human dendritic
      cells.
AB  - Recent studies from our laboratory have shown that substance P can elicit
      transcription factor activation in dendritic cells. In the present study, we
      extend these findings by demonstrating the presence of authentic substance P (NK
      1) receptors on both normal murine and human dendritic cells. Specifically, we
      demonstrate the presence of mRNA encoding NK-1 tachykinin receptors and have
      utilized specific antibodies to detect the expression of NK-1 receptor protein in
      dendritic cells by Western blot analysis and flow cytometry. These data provide a
      crucial first step in determining the potential of substance P to modulate
      dendritic cell function.

PMID- 11240025
TI  - Scavenger receptor class B type I (SR-BI) mediates adhesion of neonatal murine
      microglia to fibrillar beta-amyloid.
AB  - Class A scavenger receptors (SR-A) mediate microglial interaction with fibrillar
      beta-amyloid (fAbeta). We report here that neonatal microglia from SR-A knockout
      mice (SR-A-/-) adhere to surface-bound fAbeta, and produce reactive oxygen
      species (ROS) as efficiently as wildtype microglia; that both wildtype and SR-A-/
      microglia express SR-BI; that antibodies against SR-BI do not affect adhesion or
      ROS production by wildtype microglia, but inhibit adhesion and ROS production of
      SR-A-/- microglia to immobilized fAbeta by approximately 40%. Adhesion to fAbeta
      coated surfaces, and uptake of fAbeta by both wildtype and SR-A-/- microglia was
      almost completely inhibited by incubation with fucoidan. Thus SR-BI and SR-A
      mediate similar effector functions in neonatal microglia, which suggests that SR
      BI plays as important a role as SR-A, and can maintain the wildtype phenotype in
      SR-A-/- microglia.

PMID- 11240026
TI  - CD81 and microglial activation in vitro: proliferation, phagocytosis and nitric
      oxide production.
AB  - CD81 (TAPA), a member of the tetraspanin family of proteins, is upregulated by
      astrocytes and microglia after traumatic injury to the rat central nervous system
      (CNS). To further understand the role of CD81 in the microglial response to
      injury, we analysed the functional effects of a CD81 antibody, AMP1, on cultured
      rat microglia. We found that AMP1 suppressed microglial proliferation in a dose
      dependent manner. Furthermore, AMP1 stimulated myelin phagocytosis, probably by
      opsonizing the myelin. The phagocytosis of latex beads, as well as the production
      of nitric oxide, were not significantly influenced by AMP1. These data indicate
      that CD81 is involved in an important subset of microglial effector functions
      after CNS injury.

PMID- 11240027
TI  - Polyspecific immunoglobulins (IVIg) suppress proliferation of human (auto)antigen
      specific T cells without inducing apoptosis.
AB  - Polyspecific immunoglobulins (IVIg) have been shown to reduce disease activity in
      multiple sclerosis (MS). To investigate the mechanisms of action of IVIg, we
      studied the impact of IVIg on growth and death (apoptosis) of human (auto)antigen
      specific T cells. We observed a substantial suppression of proliferation of
      specifically activated T cells, in absence of caspase activation or DNA
      fragmentation. Further, neither susceptibility of T cells to undergo CD95
      mediated apoptosis nor expression of apoptosis-blocking bcl-2 was modulated by
      IVIg. We conclude that IVIg may inhibit the reactivity of antigen-specific T
      cells in MS through suppression of proliferation rather than modulation of
      apoptosis.

PMID- 11240028
TI  - Mediated efflux of IgG molecules from brain to blood across the blood-brain
      barrier.
AB  - Dextrans and albumin exit brain from blood following intra-cerebral injection by
      a slow process of convection with a halftime of 10-12 h in the rat. The present
      studies show that immunoglobulin G (IgG) molecules rapidly efflux from brain to
      blood across the blood-brain barrier (BBB) following intracerebral injection. The
      IgG efflux is rapid with a halftime of 48 min in the rat. The efflux of [3H]mouse
      IgG(2a) from brain to blood is competitively inhibited by intracerebral injection
      of unlabeled mouse IgG molecules, but is not inhibited by intracerebral injection
      of comparable doses of unlabeled rat albumin. The IgG efflux system has
      characteristics of an Fc receptor, as the efflux from brain is competitively
      inhibited by Fc fragments but is not blocked by F(ab')(2) fragments.
      Precipitation of brain homogenate by trichloroacetic acid indicates there is no
      significant metabolism of the IgG molecules during the experimental time period.
      In conclusion, these studies provide evidence for a BBB Fc receptor that mediates
      the reverse transcytosis of IgG molecules in the direction of brain to blood.

PMID- 11240029
TI  - Expression of functional mu-opioid receptors during T cell development.
AB  - We have examined the chemotactic responsiveness of thymocytes to selective mu-,
      kappa-, and delta-opioid agonists. Our results show that developing T cells
      migrate in response to mu-, but not kappa- or delta-opioids. The mu-opioid
      response appears to be dependent on the classical mu-opioid receptor (MOR-1)
      since the chemotactic response is blocked by a selective mu-opioid antagonist,
      and is absent in thymocytes from MOR-1-deficient mice. Flow cytometric analysis
      of the mu-opioid responsive cells shows that these cells consist predominantly of
      highly immature CD4- CD8- T cells. These results represent the first
      demonstration of the functional expression of mu-opioid receptors by developing T
      cells.

PMID- 11240030
TI  - Parental genes do not codominantly confer susceptibility to experimental
      autoimmune encephalomyelitis in F1 rats.
AB  - Lewis (LEW) and DA rats are highly susceptible to experimental autoimmune
      encephalomyelitis (EAE) induced with guinea pig myelin basic protein (MBP), but
      respond to different epitopes. The dominant epitope for LEW rats is MBP73-86, and
      disease is mediated primarily by Vbeta8.2 Th1 cells. DA rats lack conventional
      Vbeta8.2 T cells and do not respond to MBP73-86. Rather, DA rats respond to the
      cryptic epitope MBP63-81, which is not encephalitogenic for LEW rats. Responses
      to these neuroantigens were investigated in (DAxLEW) F1 hybrids to determine if
      experimental findings in inbred rats remain valid in more genetically complex
      models. Surprisingly, MBP63-81, a cryptic epitope for DA rats, induced moderate
      to-severe EAE in F1 hosts, whereas MBP73-86, the dominant LEW epitope, was only
      weakly encephalitogenic in F1 hosts. The poor clinical response to MBP73-86
      appears to be a consequence of an inability to expand Vbeta8.2 T cells. These
      results suggest that parental responses to neuroantigens are poor predictors for
      determining encephalitogenicity in F1 progeny.

PMID- 11240031
TI  - Inhibition of the adhesion step of leukodiapedesis: a critical event in the
      recovery of Guillain-Barre syndrome associated with accumulation of
      proteolytically active lymphocytes in blood.
AB  - Intraneural inflammation, that reflects emigration of immune cells from blood to
      nerve tissue, is a critical event in Guillain-Barre syndrome pathogenesis. To
      investigate the adhesion and transmigration phases of leukodiapedesis, we
      determined in a series of patients with GBS: (1) circulating levels of soluble
      forms of adhesion molecules (sICAM-1 and sVCAM-1); (2) attachment capacities of
      circulating lymphocytes to rICAM-1 and rVCAM-1; (3) fibronectin-penetrating
      capacities of circulating lymphocytes; and (4) lymphocyte intracellular
      concentrations of MMP-9 at the different phases of GBS and in healthy controls.
      Circulating levels of sVCAM-1 and sICAM-1 were above normal values at the time of
      progression, markedly increased at the time of plateau (sVCAM-1: P<0.03; sICAM-1:
      P<0.02), and tended to normalize during recovery. The percentage of cells with
      attachment capacities to rVCAM-1 and to rICAM-1 decreased from progression to
      recovery by 30 and 31%, respectively (P<0.02). The number of circulating
      lymphocytes with fibronectin penetrating capacities was lower than controls at
      the time of progression (P<0.01), then progressively increased to reach values
      higher than controls at the time of late recovery (P<0.02). Cellular
      concentrations of MMP-9 in circulating lymphocytes paralleled their fibronectin
      penetrating capacities. These results suggest early emigration of lymphocytes
      into nerve, followed by shedding of adhesion molecules from endothelium, and late
      decrease of lymphocyte adhesion capacities. Plateau and recovery are associated
      with accumulation in the vascular compartment of still proteolytically active
      lymphocytes that can no longer adhere to endothelial cells. Modulation of the
      adhesion step of leukodiapedesis may be crucially involved in the switch from
      progression to plateau of GBS.

PMID- 11240032
TI  - Elevated levels of soluble Fas and Fas ligand in cerebrospinal fluid of patients
      with AIDS dementia complex.
AB  - We measured the levels of sFas and sFasL in CSF and serum of HIV-1 infected
      patients and related them to AIDS dementia complex (ADC). Specimens were obtained
      from 51 HIV-1 infected individuals (29 with ADC) and 39 HIV negative individuals.
      The sFas was detectable in all sera and 98% of CSF specimens. Measurable levels
      of sFasL were found in 79% of the CSF and 98% of sera samples. According to the
      presence or absence of ADC, we observed significant differences in CSF sFas
      (median and IQR 116, 132 vs. 30, 23 pg/ml, P<0.001) and sFasL (median and IQR
      127, 290 vs. 15, 73 pg/ml, P<0.001) levels. The sFas in serum differed
      significantly between HIV-1 infected subjects and non-infected controls
      (P<0.001), with no correlation to ADC. On the contrary, sFasL in serum differed
      among HIV-1 infected subjects according to clinical signs of ADC. In the cross
      sectional study, the number of cells present in CSF and CD4+ T cell counts in
      blood did not correlate to the levels of CSF sFas and sFasL. Interestingly, the
      number of HIV RNA copies in CSF correlated significantly to the levels of CSF
      sFasL (P=0.001) but not to sFas in the same compartment. Antiretroviral therapy
      reduced viral load and sFas levels in CSF in the majority of patients. sFas is a
      useful marker for ADC diagnosis and follow-up during antiviral treatment.

PMID- 11240033
TI  - Chemokine receptor expression on T cells in blood and cerebrospinal fluid at
      relapse and remission of multiple sclerosis: imbalance of Th1/Th2-associated
      chemokine signaling.
AB  - The expression of chemokine receptors on lymphocytes in the blood and CSF of
      multiple sclerosis (MS) patients was analyzed at relapse and remission. Both CD4+
      and CD8+ cells in CSF at relapse were enriched for Th1-type receptors CXCR3 and
      CCR5 expression, and were reduced for Th2-type receptors CCR3 and CCR4 expression
      compared with those of the blood. CCR1 and CCR2 expressions on T cells were
      increased in CSF and blood, respectively. At remission, CCR5 expression, but not
      CXCR3 expression, was reduced in CSF CD4+ cells. A biased Th1/Th2 balance may
      play a critical role in active inflammation and CCR5 on CSF CD4+ cells is a good
      marker of the disease activity.

PMID- 11240034
TI  - Human IgM anti-GM1 autoantibodies modulate intracellular calcium homeostasis in
      neuroblastoma cells.
AB  - Increased titers of IgM anti-GM1 antibodies are present in some patients with
      Lower Motor Neuron Disease (LMND) or Motor Neuropathy (MN), but their pathogenic
      role and the mechanism of action are unclear. Previous studies have shown that
      the B subunit of Cholera Toxin (CT), which binds and crosslinks ganglioside GM1,
      modulate intracellular calcium in murine neuroblastoma cells via the activation
      of L-type voltage-dependent calcium channels (VGCC). Therefore, using a
      fluorimetric approach, we have examined the hypothesis that the pentameric IgM
      anti-GM1 antibodies, could similarly alter calcium concentration in N18
      neuroblastoma cells. Sera with human IgM anti-GM1 antibodies were obtained from 5
      patients with LMND and 2 patients with MN. Human IgG anti-GM1, IgM anti-Myelin
      Associated Glycoprotein (MAG), IgM anti-sulfatide antibodies and lectin peanut
      agglutinin (PNA), that recognizes specifically the Gal(betal-3)GalNAc epitope,
      were used as control sera. Direct application of either human IgM anti-GM1
      antibodies or the B subunit of CT to N18 neuroblastoma cells induced a sustained
      influx of manganese ions, as indicated by a quench of the intracellular fura-2
      fluorescence. Furthermore, the dihydropyridine L-type channel antagonists
      completely inhibited the manganese influx, suggesting that it is due to
      activation of an L-type VGCC. The magnitude of the influx was correlated with
      antibody titers. None of human IgG anti-GM1, IgM anti-MAG, IgM anti-sulfatide
      antibodies or PNA induce an ion influx, pointing to the selective participation
      of the pentameric IgM isotype of anti-GM1 in the modulation of L-type calcium
      channels opening. Given that L-type calcium channels are present on motor
      neurons, the modulation of L-type calcium channels by IgM GM1 antisera may have
      important implications in diseases such as LMND and MN.

PMID- 11240035
TI  - The fine specificity of the myelin oligodendrocyte glycoprotein autoantibody
      response in patients with multiple sclerosis and normal healthy controls.
AB  - Antibodies directed against the extracellular immunoglobulin (Ig)-like domain of
      the myelin oligodendrocyte glycoprotein (MOG(Igd)) mediate demyelination in
      experimental autoimmune encephalomyelitis (EAE) and are implicated in the
      immunopathogenesis of multiple sclerosis (MS). In this study we investigated the
      epitope specificity of MOG(Igd)-specific autoantibodies immunopurified from MS
      patients (n=17) and normal healthy controls (HD; n=9). ELISA, using a panel of
      synthetic MOG(Igd) peptides, revealed that the epitope specificity of this
      response was heterogeneous in both groups. The most frequently recognised
      epitopes were located in amino acid sequences (a.a.) 1-26 (13/17) and 63-87
      (15/17) in MS patients, and 14-39 (6/9) and 63-87 (6/9) in HDs, but there was no
      association between MS and any particular peptide specificity. We therefore
      investigated the ability of the immunopurified antibodies to recognise native
      MOG(Igd) expressed on at the membrane surface by FACS. Unexpectedly, antibodies
      fulfilling this essential criterion for a demyelinating antibody response were
      detected only in one of the MS samples. These results indicate that the epitope
      specificity of the human B cell response to MOG is not only heterogeneous, but
      may only mediate demyelination in a limited subset of MS patients.

PMID- 11240036
TI  - Anti-GM(2) IgM antibody-induced complement-mediated cytotoxicity in patients with
      dysimmune neuropathies.
AB  - Anti-GM2 IgM antibodies have been reported in some patients with dysimmune
      neuropathy or lower motor neuron syndrome. To determine whether these antibodies
      can induce complement-dependent cytolysis we performed a cytotoxicity assay on
      neuroblastoma cells with sera from seven patients with demyelinating dysimmune
      neuropathies and high titers of anti-GM2 IgM. As controls we used sera from seven
      patients with other anti-neural reactivities, six with the same neuropathies but
      no anti-GM2 or other anti-neural reactivity and from eight normal subjects. Of
      the seven positive sera tested, six induced complement-mediated cytotoxicity,
      while none of the controls had any relevant effect on neuroblastoma cells.
      Preincubation of positive sera with purified GM2 removed cytotoxic activity.
      Affinity purified anti-GM2 IgM had the same cytotoxic anti-GM2 effect of whole
      serum while serum or complement alone did not have any effect. In four anti-GM2
      positive patients the percentage of cell lysis correlated with anti-GM2 titers
      and with IgM staining of neuroblastoma cells while in two the cytotoxic effect
      was higher than expected from antibody titers. Complement-mediated cell lysis
      induced by anti-GM2 IgM antibodies may be a possible mechanism of neural damage
      in patients with dysimmune neuropathy and high titers of anti-GM2 IgM antibodies.

PMID- 11240037
TI  - Human focal cerebral infarctions induce differential lesional interleukin-16 (IL
      16) expression confined to infiltrating granulocytes, CD8+ T-lymphocytes and
      activated microglia/macrophages.
AB  - Focal cerebral ischemia elicits a strong inflammatory response which readily
      participates in lipid oxygenation, edema formation, apoptotic cell death and
      tissue remodeling. Within these conditions, cytokines are key players of cell
      activation and are crucial for delayed mechanisms of ischemic damage. Mature IL
      16 is an immunomodulatory cytokine, exerting CD4 dependent and independent
      effects and is characterized by chemotactic activity, induction of early gene
      phosphorylation, stimulation of pro-inflammatory IL-1beta, IL-6, TNFalpha
      expression in monocytic cells and also modulates apoptosis. We have now analyzed
      expression of IL-16 in 20 brains of patients following focal cerebral infarctions
      (FCI, n=20). Compared to normal control brains (n=3), IL-16 was expressed by
      infiltrating immune cells such as neutrophils, CD8+ lymphocytes and activated
      CD68+ microglia/macrophages accumulating in lesion associated reactive zones and
      in peri-vascular regions. IL-16+ cells accumulated significantly (P<0.0001) in
      the necrotic lesion and at bordering peri-lesional areas at day 1-2 reaching
      maximum levels at day 3-4 (P<0.0001). Also, peri-vascular IL-16+ cells reached
      maximum levels at day 3-4 (P<0.0001) following infarction and decreased after
      several weeks. During the early microglial activation period, IL-16+
      microglia/macrophages coexpress the activation antigen MRP-8. The accumulation of
      IL-16+ granulocytes, IL-16+, CD8+ lymphocytes and activated IL-16+, CD68+, CD4-
      microglia/macrophages, early after infarction suggest a CD4 independent,
      paracrine role of IL-16 in the postinjury inflammatory response, such as
      recruitment and activation of immune cells leading to microvessel clustering and
      blood-brain barrier disturbance resulting in secondary damage.

PMID- 11240038
TI  - IL-12/IL-12R system in multiple sclerosis.
AB  - IL-12/IL-12 receptor (IL-12R) system orchestrates the Th1 pathway of the immune
      system by maintaining one of the major bridges between innate and adaptive immune
      responses. Here, we studied both sides of this system in patients with multiple
      sclerosis (MS) and in controls. MS patients displayed elevated IL-12Rbeta1 and IL
      12Rbeta2 expression on PHA-activated T cells compared to healthy subjects. Higher
      percentages of IL-12Rbeta1 and IL-12Rbeta2 positive T cells in cerebrospinal
      fluid (CSF) compared to blood were observed both in MS and other neurological
      diseases (OND). In contrast, numbers of IL-12 secreting blood mononuclear cells
      (MNC) were similar in MS and controls. The functional importance of high IL
      12Rbeta2 in MS was underlined by the finding that IL-12 stimulated IFN-gamma
      production and proliferation of PHA-activated T cells correlated with levels of
      IL-12Rbeta2 expression. Our data indicates a dysregulation of the IL-12/IL-12R
      system in MS. It is suggested that even in the absence of increased IL-12 levels,
      the net effect of IL-12 might be augmented in MS by elevated expression of its
      receptor.

PMID- 11240039
TI  - Interleukin-18 is induced in acute inflammatory demyelinating polyneuropathy.
AB  - T lymphocytes of the Th1 subset producing the proinflammatory cytokine interferon
      gamma (IFN-gamma) have been implicated in the pathogenesis of immune-mediated
      diseases of the peripheral nervous system (PNS) such as the acute Guillain-Barre
      syndrome (GBS) and its animal model experimental autoimmune neuritis (EAN).
      Interleukin-18 (IL-18) is a potent IFN-gamma-inducing cytokine that is
      synthesized as an inactive precursor molecule and cleaved by caspase-1 into its
      mature active form. In our present study we analyzed the expression of IL-18 and
      caspase-1 in the nerve roots of EAN rats using reverse transcriptase-polymerase
      chain reaction and immunocytochemistry. Using an enzyme-linked immunosorbent
      assay, we furthermore determined IL-18 protein levels in paired serum and
      cerebrospinal fluid (CSF) samples from patients with GBS as well as from
      noninflammatory neurologic disease (NIND) controls. In EAN, IL-18 and caspase-1
      mRNA levels in the nerve roots increased during the stage of active disease
      progression. Immunocytochemically, both perivascular and parenchymal IL-18
      protein expression was increased in the roots of EAN rats and mainly associated
      with ED1+ macrophages stained on serial sections. IL-18 serum levels were
      significantly higher in GBS patients than in NIND controls (238+/-71 vs. 42+/-7
      pg/ml, P<0.001). Our data implicate the Th1-inducing cytokine IL-18 in the
      pathogenesis of acute immune-mediated PNS demyelination.

PMID- 11240040
TI  - Restricted IgG1 subclass of anti-Yo antibodies in paraneoplastic cerebellar
      degeneration.
AB  - Paraneoplastic cerebellar degeneration (PCD) occurs as a non-metastatic
      manifestation of cancer in a small proportion of patients with certain breast or
      gynaecological tumours, and is characterised by widespread Purkinje cell loss.
      Antibodies against a Purkinje cell cytoplasmic antigen, called Yo, that is
      expressed by the tumours, are present in the majority of these patients, but the
      pathogenic role of the antibodies is not clear. To characterise further the
      immune response in these cases, 13 anti-Yo positive sera were tested for IgG
      subclasses by immunohistochemistry and western blotting and, in four cases, PHA
      stimulated cytokine secretion by peripheral blood lymphocytes was measured.
      Surprisingly, anti-Yo antibodies were entirely restricted to the IgG1 subclass,
      whereas antibodies against the small cell cancer-associated antigen, Hu, were
      found in all four IgG subclasses. There was a trend towards raised IgG1 levels in
      the total IgG of the anti-Yo positive patients and, in two, PHA-stimulated
      peripheral blood lymphocytes secreted raised levels of IFN-gamma. By contrast, in
      the other two cases tested, raised levels of IL-4 were secreted. Patients with
      PCD associated with anti-Yo antibodies appear to have strong immune responses
      that are polarised with respect to the IgG subclass and Th cytokine profiles.

PMID- 11240041
TI  - Distribution and abundance of Gram-positive bacteria in the environment:
      development of a group-specific probe.
AB  - We developed a 16S rRNA-targeted oligonucleotide probe (S-P-GPos-1200-a-A-13) for
      the Gram-positive bacteria, confirmed its specificity by database searches and
      hybridization studies, and investigated the effects of humic acids on membrane
      hybridizations with this probe. S-P-GPos-1200-a-A-13 was used to estimate the
      abundance of Gram-positive populations in the bovine rumen and Lake Michigan
      sediments. This probe should be useful for studies of the environmental
      distribution of Gram-positive bacteria and the detection of uncultured,
      phylogenetically Gram-positive bacteria with variable or negative Gram staining
      reactions, and could serve for Gram staining in some diagnostic settings.

PMID- 11240042
TI  - Rapid detection of Bacillus stearothermophilus using impedance-splitting.
AB  - An impedance splitting method was used to detect Bacillus stearothermophilus in
      suspension and attached to stainless steel surfaces. The effects of bacterial
      metabolism on the impedance of the culture medium and the ionic layers of the
      measuring electrodes were recorded using the BacTrac 4000 microorganism growth
      analyser. Impedance changes were measured at 55 degrees C. Seven of the eight
      media produced changes in the electrode impedance (E-value) and all media
      produced negligible changes in the impedance of the culture medium (M-value).
      Good correlations were obtained between cell numbers and the E-value measured
      over 18 h (r > 0.9) for the two strains of B. stearothermophilus tested in
      trypticase soy broth. The E-value correlations were used to estimate the numbers
      of both vegetative and spore forms of B. stearothermophilus as either planktonic
      or adhered cells. For the detection of B. stearothermophilus using impedance,
      only methods where the E-value impedance is recorded, can be used.

PMID- 11240043
TI  - Improved preparation of high molecular weight DNA for pulsed-field gel
      electrophoresis from mycobacteria.
AB  - Molecular typing is now widely used to aid and supplement conventional
      epidemiological studies of mycobacterial diseases. Pulsed-field gel
      electrophoresis (PFGE), in which the entire genome can be represented as a
      distinct pattern of DNA restriction fragments, is a particularly powerful tool in
      epidemiology for the determination of clonal identity of bacteria providing
      information for understanding and controlling the spread of disease. Application
      of PFGE to the study of mycobacterial diseases has been limited because isolation
      of high-quality genomic DNA from mycobacterial sources has proved problematic.
      Here we report a simple, highly effective method for the preparation of high
      molecular weight DNA from a range of mycobacterial species. Cultures are
      continuously stirred and are homogeneous. This enables accurate quantification.
      The presence of detergent in buffers keeps the cells in suspension throughout
      preparation enabling efficient lysis. In addition, it is compatible with heat
      inactivation of pathogenic mycobacteria and all of the preparation procedures can
      be carried out with a category III facility. This standardised method of
      preparation of DNA from mycobacteria means that PFGE should now be evaluated as a
      method for typing these organisms and it may be particularly important as a means
      of typing less well-characterised mycobacteria for which other techniques are not
      available.

PMID- 11240044
TI  - Identification of novel Mycoplasma hyorhinis gene fragments by differential
      display analysis of co-cultures.
AB  - Mycoplasmas are a diverse group of wall-less prokaryotes that have evolved an
      unusually small genome by adopting a parasitic mode of life. Recently, intense
      efforts have been made to sequence mycoplasma genomes and to define a minimal
      genome using mycoplasma as a model. Due to their parasitic nature, mycoplasma
      species are often difficult to cultivate, making it challenging to identify and
      sequence mycoplasma genes. In this report, we describe a method for identifying
      mycoplasma gene fragments from co-cultures using differential display analysis.
      Using this technique, we have identified fragments of seven putative genes from
      Mycoplasma hyorhinis. Sequence similarities suggest that four of these genes are
      members of the proposed minimal mycoplasma genome. The application of
      differential display analysis to co-cultures should be useful in the
      identification of genes from a variety of pathogenic organisms that are difficult
      to cultivate without a host.

PMID- 11240045
TI  - Optimization of a fluorescent-based phosphor imaging dot blot DNA hybridization
      assay to assess E. coli virulence gene profiles.
AB  - To increase the efficiency and consistency in screening Escherichia coli for
      virulence genes, a Phosphor Imager was adopted for signal detection in Dot Blot
      DNA hybridization replacing X-ray film read by eye. We assessed not only the
      reliability of the instrument-based procedure, but the impact of going from an
      outcome measured by visualization on a semi-quantitative scale to a digitized
      readout on an interval scale. We analyzed technical and biological variability of
      the assay and the factors contributing to the variability. In spite of high
      variability both within and between membranes in the Phosphor Imager readings, we
      were able to define classification rules for gene presence that were remarkably
      consistent. Using the X-ray film signal detection procedure with Southern
      confirmation as a gold standard, we obtained a sensitivity and specificity of 87
      99% for a rule requiring no retesting for all but one gene probe.

PMID- 11240046
TI  - Efficient isolation of total RNA from Clostridium without DNA contamination.
AB  - Several molecular techniques require high-quality RNA, free from DNA. Various
      methods have been described to obtain RNA to be used in expression studies or as
      starting material in differential display-reverse transcriptase (dd-RT-PCR), for
      which high-quality RNA free from DNA is an essential requirement. In this report,
      we compare three different methods to isolate RNA from Gram-positive bacteria:
      (1) An acid-phenol extraction protocol. (2) The "RNeasy mini kit" from QIAGEN
      (Valencia, CA, USA). (3) The "SV Total RNA Isolation System" from Promega
      (Madison, WI, USA).The QIAGEN-kit delivers the highest amount of RNA with the
      highest purity. Slot blot analysis and dd-RT-PCR confirm the absence of DNA
      contamination and Northern blot analysis and dd-RT-PCR show high quality of the
      extracted RNA. This RNA extraction method thus addresses current problems by
      permitting rapid and safe isolation with high yields of intact RNA for subsequent
      analysis.

PMID- 11240047
TI  - Methods for detecting acylated homoserine lactones produced by Gram-negative
      bacteria and their application in studies of AHL-production kinetics.
AB  - In the process of evaluating the role of acylated homoserine lactones (AHLs) in
      food-spoiling Gram-negative bacteria, we have combined a range of bacterial AHL
      monitor systems to determine the AHL-profile and the kinetics of AHL-production.
      AHL production from 148 strains of Enterobacteriaceae isolated from foods was
      tested using Escherichia coli pSB403 (LuxR), Agrobacterium tumefaciens A136
      (TraR) and both induction and inhibition of Chromobacterium violaceum CV026
      (CviR). All strains except one was found to produce AHL(s). In no case could a
      single monitor system identify more than 64% of the Enterobacteriaceae as AHL
      producers, showing that the simultaneous use of monitor strains is required in
      the process of screening bacterial populations for AHL-production. AHLs from 20
      selected strains were profiled by thin layer chromatography. Most strains
      produced more than one AHL with 3-N-oxo-hexanoyl homoserine lactone being the
      most prominent. It was found that the simultaneous use of monitor strains in the
      top-layer was necessary for the detection of (presumably) all the AHLs. An agar
      well-diffusion assay based on A. tumefaciens pDZLR4 was used for quantifying AHLs
      from bacterial supernatants and enabled an assessment of the kinetics of AHL
      production of 3 strains (Serratia proteamaculans strain B5a, Erwinia carotovora
      ATCC 39048 and V. fischeri strain MJ-1). As expected, the production of AHL
      (OHHL) and luminescence in Vibrio fischeri strain MJ-1 increased faster than
      growth indicating up-regulation of the AHL regulated phenotype and auto-induction
      of AHL production. In contrast, production kinetics of AHL (OHHL) in the two
      Enterobacteriaceae indicated lack of auto-induction.

PMID- 11240048
TI  - Design and evaluation of PCR primers to amplify bacterial 16S ribosomal DNA
      fragments used for community fingerprinting.
AB  - Denaturing gradient gel electrophoresis of PCR-amplified 16S ribosomal DNA (rDNA)
      fragments has frequently been applied to the fingerprinting of natural bacterial
      populations (PCR/DGGE). In this study, sequences of bacterial universal primers
      frequently used in PCR/DGGE were compared with 16S rDNA sequences that represent
      recently proposed divisions in the domain Bacteria. We found mismatches in 16S
      rDNA sequences from some groups of bacteria. Inosine residues were then
      introduced into the bacterial universal primers to reduce amplification biases
      caused by these mismatches. Using the improved primers, phylotypes affiliated
      with Verrucomicrobia and candidate division OP11, were detected in DGGE
      fingerprints of groundwater populations, which have not been detected by PCR/DGGE
      with conventional universal primers.

PMID- 11240050
TI  - Utility of high performance liquid chromatography/electrospray/mass spectrometry
      of polar lipids in specifically Per-13C labeled Gram-negative bacteria DA001 as a
      tracer for acceleration of bioremediation in the subsurface.
AB  - Specific fatty acids from phosphatidylglycerol (PG) and phosphatidylethanolamine
      (PE) recovered from a per 13C-labeled bacteria can be detected in environmental
      samples and used as measures of bacterial transport in the subsurface. Detection
      of palmitic acid (16:0) and oleic acid (18:1) at m/z 271 (255+16) and 299
      (281+18) as negative ions in PG and PE separated by high performance liquid
      chromatography (HPLC) and detected after up-front collisionally induced
      dissociation (CID) utilizing electrospray (ES) mass spectrometry (MS) provided
      sufficient sensitivity and specificity for detection in the presence of the
      indigenous microbiota. Application of tandem mass spectrometry (MS/MS) in the
      multiple reaction monitoring (MRM) was use to monitor selected transitions. MRM
      can increase the sensitivity so that polar lipids recovered from cell densities
      currently at about 10(4) cells/sample can be detected. This technology provides a
      non-intrusive mechanism for monitoring the distribution of bacteria added to
      accelerate in situ bioremediation of subsurface sediments.

PMID- 11240049
TI  - Development of two real-time quantitative TaqMan PCR assays to detect circulating
      Aspergillus fumigatus DNA in serum.
AB  - Several PCR assays have been developed for detecting Aspergillus fumigatus DNA in
      blood of patients with invasive aspergillosis. However, the best blood fraction
      to be assayed has not been defined and the multicopy genes used as the DNA
      targets for amplification not characterized. Firstly, we developed a real-time
      PCR assays based on the TaqMan technology targeted to a single copy gene. To
      compare serum, white cell pellet, and plasma for effectiveness as blood assay
      fractions, we spiked whole blood with A. fumigatus DNA and processed these
      fractions similarly. The difference between white cell pellet and serum was not
      significant. In contrast, the yield from plasma was 10 times lower than from
      serum. Then, we compared serum processed immediately or after 24 h at room
      temperature and observed a lower yield after 24 h. Secondly, a real-time PCR
      assay targeted to a mitochondrial gene was also developed. The copy number was
      estimated between 9 and 10 mitochondrial genes per single copy gene. Therefore,
      we recommend serum, stored and frozen as soon as possible, to be used for
      detecting circulating A. fumigatus DNA for diagnosis. Moreover, the mitochondrial
      multicopy gene was characterized in order to compare results from different
      patients.

PMID- 11240051
TI  - Disorders in trunk rotation during walking in patients with low back pain: a
      dynamical systems approach.
AB  - OBJECTIVE: (1) To introduce an evaluation tool for the assessment of walking
      disorders in low back pain patients. (2) To investigate whether walking patterns
      in low back pain patients are different from those of control subjects. DESIGN:
      Relative phase measures of movement coordination are applied in the assessment of
      trunk function in a small group of patients with non-specific low back pain and
      in control subjects. BACKGROUND: Normal subjects change the coordination of
      pelvic and thoracic rotations from an in-phase to an out-of-phase pattern with
      increasing walking speed. Low back pain patients may have a reduced ability to
      counter rotate pelvis and thorax at higher walking speeds (from 1.0 m/s onwards)
      as a result of hyperstable coordination patterns. METHODS: Six patients with non
      specific low back pain and six healthy control subjects walked on a treadmill at
      comfortable walking speeds and during a systematic variation of the treadmill
      velocity. Coordination of arm and leg movements as well as of pelvic and thoracic
      rotations was analyzed using a relative phase algorithm. RESULTS AND CONCLUSIONS:
      The comfortable walking speed was reduced in the patient group. In contrast to
      the control subjects, four of the six patients were not able to establish an out
      of-phase coordination pattern between thorax and pelvis at higher walking speeds.
      This coincided with an increased stability of movement coordination, indicating
      guarded behavior. In addition, an increased asymmetry between the phase-relations
      of left and right side of the body was found in some of the patients.

PMID- 11240052
TI  - MRI-derived moment-arms of the female and male spine loading muscles.
AB  - OBJECTIVE: Develop a comprehensive gender-specific database of trunk muscle
      moment-arms across multiple levels of the lower thoracic and lumbar spine,
      determine if gender differences exist across the different vertebral levels, and
      develop prediction equations for the moment-arms as a function of external
      anthropometric measures. DESIGN: This study quantified trunk muscle moment-arms
      relative to the spine from T(8) to S(1) of male and female spine loading muscles.
      BACKGROUND: Knowledge of trunk muscle geometry is important for biomechanical
      modeling of the low back and for understanding of spinal loading. However, there
      currently is a lack of comprehensive data regarding the moment-arms of the female
      spine loading muscles. Additionally, little is known regarding gender differences
      in moment-arms for the same muscles. METHODS: Magnetic resonance imaging scans
      through the vertebral bodies from T(8) through S(1) were performed on 20 females
      and 10 males. Moment-arms in the coronal and sagittal plane between the muscle
      centroid and vertebral body centroid were recorded at each vertebral level.
      Linear regression techniques taking into account anthropometric measures were
      utilized to develop prediction equations for the moment-arms for each muscle.
      RESULTS: Anthropometric measures were better predictors of coronal plane moment
      arms than sagittal plane moment-arms for both genders. Measures consisting of
      height and weight were consistent predictors of female moment-arms. Measures
      about the xyphoid process and combinations of height and weight were consistent
      predictors of coronal plane moment-arms for males at several lower lumbar levels.
      Males exhibited larger moment-arms than for females, for most muscles at most
      levels. CONCLUSIONS: Trunk muscle moment-arms of females and males are different,
      and should be considered in the development of biomechanical models of the torso.
      Similar to other studies, external anthropometric measures were better predictors
      of coronal plane moment-arms than sagittal plane moment-arms.

PMID- 11240053
TI  - Sit-to-stand at different periods of pregnancy.
AB  - OBJECTIVE: This study was performed to determine the biomechanics of chair rising
      by pregnant women. DESIGN: Relative body joint position and ground reaction
      forces were measured by a motion analysis system and one force plate. BACKGROUND:
      Physiological and psychological changes during pregnancy impose postural demands
      and limit the performance of daily living activities such as rising from sitting
      to standing position. METHODS: Twenty-four pregnant women, divided into three
      groups, were studied performing sit-to-stand transition from an armless and
      adjustable chair. By kinematic and kinetic analysis, the angles and moments of
      hip, knee and ankle joints were investigated. RESULTS: The chair height has great
      influence on knee joint and hip joint moments, but less on ankle joints. In the
      third trimester for all chair heights, because of a marked increase in abdominal
      depth, the maximum hip moment is significantly less than that in first trimester,
      while the maximum knee moment is significantly larger. Pregnant women in third
      trimester produced larger knee moment during sit-to-stand transition from lower
      chair height. CONCLUSIONS: The mechanism of sit-to-stand is affected by the
      physical changes of pregnant women at different periods of pregnancy, e.g.
      increased loading of knee joint and decreased hip joint moment, especially in the
      last trimester period of pregnancy.

PMID- 11240054
TI  - Head movement during sudden base translations as a measure of risks for falls in
      the elderly.
AB  - OBJECTIVE: To determine whether head movement in response to a sudden platform
      translation differs between healthy young subjects and healthy elderly with and
      without, bipedal sensory loss. DESIGN: A cross-sectional study with four-way
      comparison on subject grouping and three test conditions. BACKGROUND: Head
      movement has been used as a measure of balance in the elderly during voluntary
      movements. Studies during involuntary movement, however, are limited. Moreover,
      it is not clear how head movement during involuntary activities relates to
      postural balance and susceptibility to falls. METHODS: Head movement during a
      sudden base translation was measured in three subject groups: 9 healthy young, 10
      healthy elderly adults and 10 elderly adults with vibratory sensation loss under
      the feet. The surface compliance of the supporting base, the direction of the
      base translation and the visual condition were all varied. RESULTS: There were
      significant differences among the three groups in head range of excursion (5
      degrees, 9 degrees, 13 degrees for the young, elderly, and elderly with severe
      vibratory sensation loss, respectively), onset time (120, 150, 180 ms), and the
      time from peak to peak (38, 29, 25 ms). A backward base movement increased the
      head movement more than a forward base movement. CONCLUSIONS: During sudden base
      translation balance tasks, head movement is significantly increased in the
      elderly, especially in those elderly adults who are susceptible to falls. The
      results suggest that an increased head movement in the elderly might be an
      indication of increased risks for falls.

PMID- 11240055
TI  - Fatigue-induced changes in decline running.
AB  - OBJECTIVE: Study the relation between muscle fatigue during eccentric muscle
      contractions and kinematics of the legs in downhill running. DESIGN: Decline
      running on a treadmill was used to acquire data on shock accelerations, muscle
      activity and kinematics, for comparison with level running. BACKGROUND: In
      downhill running, local muscle fatigue is the cause of morphological muscle
      damage which leads to reduced attenuation of shock accelerations. METHODS:
      Fourteen subjects ran on a treadmill above level-running anaerobic threshold
      speed for 30 min, in level and -4 degrees decline running. The following were
      monitored: metabolic fatigue by means of respiratory parameters; muscle fatigue
      of the quadriceps by means of elevation in myoelectric activity; and kinematic
      parameters including knee and ankle angles and hip vertical excursion by means of
      computerized videography. Data on shock transmission reported in previous studies
      were also used. RESULTS: Quadriceps fatigue develops in parallel to an increasing
      vertical excursion of the hip in the stance phase of running, enabled by larger
      dorsi flexion of the ankle rather than by increased flexion of the knee.
      CONCLUSIONS: The decrease in shock attenuation can be attributed to quadriceps
      muscle fatigue in parallel to increased vertical excursion of the hips.

PMID- 11240056
TI  - A dynamical systems investigation of lower extremity coordination during running
      over obstacles.
AB  - OBJECTIVE: To investigate intralimb coordination during running over a level
      surface and over obstacles of three different heights. DESIGN: The phasing
      relationships between the foot and leg motions in the frontal plane, and the
      shank and thigh motions in the sagittal plane were used to compare patterns of
      coordination. BACKGROUND: The coordinated actions of lower extremity segments are
      necessary to absorb the impact forces generated during running. The behavioral
      patterns of these segments can be studied under changing task demands using
      analysis techniques from the Dynamical Systems Theory. METHODS: Ten subjects ran
      at their self-selected pace under four conditions: over a level surface and over
      obstacles of different heights (5%, 10%, 15% of their standing height). A force
      platform was used to record impact forces during landing after obstacle
      clearance, while kinematics were collected using a two-camera system. RESULTS:
      The increases in obstacle height resulted in significant changes in impact forces
      (34% increase between the two extreme conditions) and more in-phase relationships
      between the segments during early stance. No changes were observed in the
      variability of the phasing relationships. CONCLUSIONS: The coordination changes
      observed might be compensatory strategies aimed to reduce forces and potential
      injury. However, since the impact forces still increased significantly, it is
      also possible that the observed changes might be at-risk movement patterns
      predisposing runners to injury.

PMID- 11240057
TI  - Augmentation of a ruptured posterior cruciate ligament provides normal knee joint
      stability during ligament healing.
AB  - OBJECTIVE: To identify an augmentation technique which would provide mechanical
      protection for the healing posterior cruciate ligament. DESIGN: Six human knee
      specimens were tested in vitro for posterior knee joint stability after
      augmenting the cut posterior cruciate ligament by six different techniques using
      a resorbable double strand Polydioxanone augmentation device. BACKGROUND: A fresh
      isolated rupture of the posterior cruciate ligament is often treated
      conservatively. Results have shown that it can heal, but ligament elongations
      occur frequently. Therefore a method is needed to provide posterior knee joint
      stability during ligament healing. METHODS: The effect of different femoral
      augmentation insertions on posterior knee stability was tested by recording the
      antero-posterior (AP) position of the tibia and the augmentation force. Testing
      was performed during flexion--extension cycles and under posterior shear loads.
      RESULTS: The insertion combination that proved to stabilize the joints best
      consisted of one augmentation strand leading along the antero-lateral posterior
      cruciate ligament fibres and inserting at the distal end of the Blumensaat line
      and one strand leading along the posteriormedial fibres and inserting in the
      middle of the Blumensaat line. AP translations similar to those occurring in
      healthy knee joints could be achieved. CONCLUSIONS: It is possible to restore
      normal posterior knee joint stability by implanting a double strand augmentation
      device. This can help a posterior cruciate ligament to heal under non-elongated
      conditions.

PMID- 11240058
TI  - Tibiofemoral joint forces during maximal isokinetic eccentric and concentric
      efforts of the knee flexors.
AB  - OBJECTIVE: The examination of muscular and tibiofemoral joint forces during
      maximal efforts of the knee flexors. DESIGN: The muscular and tibiofemoral joint
      knee forces during eccentric and concentric isokinetic efforts of the knee
      flexors were determined using a two-dimensional mathematical model. BACKGROUND:
      The examination of joint and muscle loading during isokinetic movements is
      important for the determination of safety of this exercise. METHODS: Ten healthy
      males performed three maximal isokinetic concentric and eccentric efforts of the
      knee flexors at angular velocities of 30 degrees s(-1), 90 degrees s(-1), 120
      degrees s(-1) and 150 degrees s(-1). The muscular, tibiofemoral shear and
      compressive joint forces were determined using a two-dimensional model. RESULTS:
      The maximum muscular force ranged from 3.44 (Standard deviation, 1.32) times body
      weight to 6.19 (1.78) times body weight. The tibiofemoral compressive force
      ranged from 2.62 (1.17) times body weight to 5.89 (1.99) times body weight
      occurring at angles ranging from 0 degrees to 40 degrees of knee flexion. The
      posterior shear force ranged from 2.61 (1.33) times body weight to 3.89 (1.62)
      times body weight and was observed at angles ranging from 50 degrees to 80
      degrees of knee flexion. Two-way analysis of variance designs indicated
      significant effects of type of muscle action and angular velocity on muscle and
      compressive forces (P<0.05). In contrast, the shear force was not affected by the
      type of muscle action or the angular velocity (P>0.05). CONCLUSIONS: Isokinetic
      efforts of the knee flexors induce high tibiofemoral joint forces, especially
      during high-speed eccentric tests.

PMID- 11240059
TI  - Quantitative measurement of ankle passive flexibility using an arthrometer on
      sprained ankles.
AB  - OBJECTIVE: The purpose of this study was to quantitatively examine the
      flexibility of sprained ankles using an arthrometer device and compare the
      differences in flexibility between ankles following the first sprains and ankles
      with repeated severe sprains and chronic symptoms. DESIGN: A retrospective in
      vivo study was used. BACKGROUND: Many in vitro studies have demonstrated a
      significant role of joint flexibility in determining mechanical laxity of human
      cadaveric ankles after sectioning of the lateral ligaments, but few in vivo
      studies have used the technique to provide objective measurement on the sprained
      ankles. Furthermore, there is a lack of extensive studies that compared the
      difference in the ankle flexibility between ankles following the first sprain and
      ankles with multiple repeated severe sprains and chronic symptoms. METHODS: A
      total of 27 subjects with unilateral ankle sprains participated in this study.
      The subjects were divided into a first injury group (group A, n=12) and a chronic
      symptom group (group B, n=15) based on the history of their ankle injuries. The
      ankle flexibility in anterior drawer and inversion/eversion tests was measured in
      both ankles of the subjects using an arthrometer device, the ankle flexibility
      tester -- a six-degree-of-freedom instrumented linkage used for measurements of
      applied forces/moments and resultant rotations and/or translations of the ankle
      joint complex. The difference in ankle flexibility between the injured ankle and
      the contralateral intact side was analyzed. RESULTS: The flexibility in anterior
      drawer test of the injured ankles significantly increased compared to the intact
      ankles of the same individual in group B, but the same difference was not
      significant in group A. There were more subjects in group B (46.6%) than in group
      A (33.3%) who showed a sign of mechanical laxity in their injured ankles.
      CONCLUSIONS: The results indicated that the approach with measurement of ankle
      flexibility may be a potential tool used to detect the mechanical laxity in the
      sprained ankles. A tendency was found that patients with multiple ankle sprains
      and chronic symptoms had a higher occurrence rate of mechanical laxity. The
      result of the present study may also be interpreted that the ankles with
      mechanical laxity had higher risk of re-injury and leading to chronic symptoms.

PMID- 11240060
TI  - Mechanical properties of the human achilles tendon.
AB  - OBJECTIVE: To determine whether the human Achilles tendon has higher material
      properties than other tendons and to test for strain rate sensitivity of the
      tendon. DESIGN: Mechanical testing of excised tendons. BACKGROUND: While the
      human Achilles tendon appears to experience higher in vivo stresses than other
      tendons, it is not known how the Achilles tendon's material properties compare
      with the properties of other tendons. METHODS: Modulus, failure stress, and
      failure strain were measured for excised human Achilles tendons loaded at strain
      rates of 1% s(-1) and 10% s(-1). Paired t-tests were used to examine strain rate
      effects, and average properties from grouped data were used to compare the
      Achilles tendon's properties with properties reported in the literature for other
      tendons. RESULTS: Failure stress and failure strain were higher at the faster
      strain rate, but no significant difference in modulus was observed. At the 1% s(
      1)rate, the mean modulus and failure stress were 816 MPa (SD, 218) and 71 MPa
      (SD, 17), respectively. The failure strain was 12.8% (SD, 1.7) for the bone
      tendon complex and 7.5% (SD, 1.1) for the tendon substance. At the 10% s(-1)
      rate, the mean modulus and failure stress were 822 MPa (SD, 211) and 86 MPa (SD,
      24), respectively. The mean failure strain was 16.1% (SD, 3.6) for the bone
      tendon complex and 9.9% (SD, 1.9) for the tendon substance. These properties fall
      within the range of properties reported in the literature for other tendons.
      CONCLUSIONS: The material properties of the human Achilles tendon measured in
      this study are similar to the properties of other tendons reported in the
      literature despite higher stresses imposed on the Achilles tendon in vivo.

PMID- 11240061
TI  - Prediction of strength of cortical bone in vitro by microcomputed tomography.
AB  - OBJECTIVE: The aim of this study was to evaluate the predictive value of bone
      mineral density and intracortical porosity measured by microcomputed tomography
      for the strength of cortical bone biopsies. DESIGN: Experimental study comparing
      the predictive value of bone mineral density and of intracortical porosity
      determined in vitro by microcomputed tomography for the mechanical properties of
      cortical bone cylinders. BACKGROUND: The assessment of cortical bone strength
      might be relevant for the prediction of fracture risk or the choice of suitable
      therapy strategies in orthopaedic surgery. The predictive value of cortical
      density for the mechanical properties is discussed controversially. The relevance
      of intracortical porosity measured by histomorphometry has been established, but
      the predictive value of porosity determined by microcomputed tomography remains
      to be explored. METHODS: Femoral cortical bone specimens from the mid diaphysis
      of 24 patients were harvested during total hip replacement procedure at the
      location, where a diaphyseal hole (diameter 4.5 mm) was drilled in order to
      reduce the intramedullary pressure. In vitro intracortical porosity and bone
      mineral density measurements by microcomputed tomography were compared with
      strength and elastic modulus assessed by a compression test transverse to the
      Haversian systems of the same specimens. RESULTS: Significant negative
      correlations were found between porosity measured by microcomputed tomography
      scans and yield stress, stiffness and elastic modulus (P<0.001), however, the
      positive correlations between bone mineral density and mechanical parameters were
      stronger (P<0.0001). The mechanical parameter best predicted by mineral density
      as well as by porosity was yield stress (r=0.72,P<0.0001;r=-0.64,P<0.001).
      CONCLUSIONS: Bone mineral density determined by microcomputed tomography imaging
      in vitro may be a potent method to predict mechanical properties of cortical bone
      non-destructively. The application in vivo remains to be explored.

PMID- 11240062
TI  - Predictive value of Singh index and bone mineral density measured by quantitative
      computed tomography in determining the local cancellous bone quality of the
      proximal femur.
AB  - OBJECTIVE: The purpose of this study was to assess the predictive value of the
      Singh index as well as quantitative computed tomography for the in vitro local
      mechanical competence of the cancellous bone of the proximal femur. DESIGN: An
      experimental study examining the relation between mechanical properties and bone
      mineral density of the femoral neck determined in vitro and the clinical
      estimated Singh index on X-rays. BACKGROUND: Evaluation of the predictive value
      of the Singh index, an inexpensive and simple technique for the mechanical
      properties of the cancellous bone of the proximal femur. METHODS: The bone
      quality of the proximal femur of 34 patients undergoing total hip replacement was
      estimated by roentgenography using the Singh index. Bone mineral density was
      quantified by quantitative computed tomography using cylindrical cancellous bone
      biopsies harvested during the total hip replacement procedure by a new biopsy
      method. The mechanical properties of the bone specimens (Young's modulus,
      strength and maximum energy absorption E(max)) were measured by mechanical
      testing of the bone biopsies. RESULTS: A strong correlation of the Singh index
      versus material properties of cancellous bone was noted (r=0.66 for Young's
      modulus, r=0.73 for strength and r=0.69 for E(max), P<0.0001). The correlations
      of bone mineral density measured by quantitative computed tomography versus
      Young's modulus, strength and energy absorption E(max) were significant. Strength
      was predicted best (r=0.82; P<0.0001), followed by E(max) (r=0.79; P<0.0001) and
      Young's Modulus (r=0.73; P<0.0001). CONCLUSIONS: We conclude, that assessment of
      bone mineral density by quantitative computed tomography is a reliable and
      precise method for the estimation of cancellous bone material properties. The
      Singh index provides a rough estimate for the mechanical competence of the
      proximal femur. It is inexpensive, simply to assess and can in some cases replace
      the measurement of bone mineral density, notably in cases of marked decrease in
      bone density.

PMID- 11240063
TI  - Paraspinal muscle EMG fatigue testing with two methods in healthy volunteers.
      Reliability in the context of clinical applications.
AB  - OBJECTIVE: Comparison of the accuracy of surface electromyogram for back muscle
      endurance assessment with two different tests. DESIGN: Test-retest measurements
      in 16 healthy volunteers on two separate occasions for each test under controlled
      conditions. BACKGROUND: Back muscle endurance is considered important in low back
      pain rehabilitation. Reliability of paraspinal muscle endurance assessment is a
      pre-requisite for accurate and meaningful clinical applications of the technique.
      METHODS: All participants performed each test twice. A direct comparison was made
      between two popular fatigue testing methods, the modified Biering-Sorensen and a
      60% maximum voluntary isometric contraction in the upright position during which
      time fatigue was assessed from the electromyogram spectral and amplitude
      analysis. RESULTS: Reproducibility of initial median frequency was excellent for
      both tests. Normalised median frequency slope values were more reliable with the
      60% maximum voluntary contraction upright test. The clinical applicability of
      these measures in detecting significant differences after patient rehabilitation
      is recommended. Root mean square had very large between-day error for both tests.

PMID- 11240064
TI  - Heavy metal speciation and leaching behaviors in cement based
      solidified/stabilized waste materials.
AB  - A circuit board printing factory sludge containing high concentrations of copper,
      zinc and lead was stabilized and solidified (S/S) with different portions of
      ordinary Portland cement (OPC) and pulverized fly ash (PFA). The chemical
      speciation and leaching behavior of heavy metals in these cement-based waste
      materials were studied by different sequential extraction procedures, standard
      toxicity characteristic leaching procedure (TCLP) and progressive TCLP tests. The
      sequential extraction results showed that more than 80% of Cu, Pb and Zn were
      associated with Fraction 2 (weak acid soluble, extracted with 1M NaOAc at pH 5.0
      with a solid to liquid ratio of 1:60). This indicated that the heavy metals could
      exist in the S/S matrix as metal hydrated phases or metal hydroxides
      precipitating on the surface of calcium silicate hydrates (C-S-H), PFA and sludge
      particles. The progressive TCLP test results and MINTEQA2 calculation also showed
      the importance of Cu and Zn oxides during the leaching process. The leaching
      behaviors of these metals in the S/S waste materials were mainly controlled by
      the alkaline nature and acid buffering capacity of the S/S matrix. During the
      progressive TCLP tests, the alkaline conditions and acid buffering capacity of
      the matrix decreased with the dissolution of calcium hydroxide and C-S-H,
      therefore, the leaching of heavy metals in the S/S waste materials increased. The
      leaching of heavy metals in the S/S materials can be considered as a pH dependent
      and corresponding metal hydroxide solubility controlled process.

PMID- 11240065
TI  - Removal of styrene vapor from waste gases by a trickle-bed air biofilter.
AB  - The trickle-bed air biofilter (TBAB) performance for the removal of high-strength
      styrene was evaluated under different gas flow rates and influent concentrations.
      Under pseudo-steady-state conditions, the elimination capacity increased but the
      removal efficiency decreased with the increase of styrene loading. More than 90
      and 80% removal efficiencies were achieved for influent styrene loadings below 32
      and 55g/m(3)/h, respectively. The TBAB appears to be an effective treatment
      process for controlling high-strength styrene emission under low-to-medium
      loading conditions, and the effectiveness could be maintained over 140 days of
      laboratory operation.

PMID- 11240066
TI  - Pollutants in incineration flue gas.
AB  - Previous studies have shown that pollutants from incineration include heavy
      metals, organic compounds, particulate and acid gas. However, most studies on a
      single pollutant, it is rare for a study to concentrate on all possible
      pollutants and the relations between these pollutants under various incineration
      conditions. The objective of this work was to experimentally study the effect of
      different operating conditions on the pollutants emitted during incineration and
      the relations between these pollutants. The operating conditions of the
      experiments included the temperature of the combustion chamber and the species of
      organics. The findings indicated that the concentration of hydrogen chloride
      (HCl) in the presence of polyvinyl chloride (PVC) was higher than that of sodium
      chloride (NaCl). Regardless of what Cl-containing feedstock was added, the
      concentration of chromium (Cr) was constant. When organic chloride was added, Cr
      was the main metallic element which influenced the formation of polycyclic
      aromatic hydrocarbons (PAHs). On the other hand, when inorganic chloride (NaCl)
      was added, lead (Pb) was the major element.

PMID- 11240067
TI  - Migration of lead from unplasticized polyvinyl chloride pipes.
AB  - The effect of water quality parameters, such as water pH, temperature, and total
      dissolved solids (TDS), and direct exposure to UV-radiation on the migration of
      lead, tin and other metal stabilizers, such as calcium, cadmium, and barium from
      unplasticized polyvinyl chloride (uPVC) pipes were investigated using locally
      manufactured pipes. Specimens of 1m were used to investigate the effect of water
      quality parameters using the circulatory method. To investigate the effect of UV
      radiation, specimens of 33cm long were used throughout the research. The
      investigation was carried out, using the static method at different times of
      exposure to the UV-radiation. The concentrations of lead, tin, and other metal
      stabilizers in the water were evaluated using the inductively coupled argon
      plasma (ICAP) technique. The results on the effect of water quality parameters
      showed that water pH, temperature, TDS, and time of water circulation were all
      having an effect on the migration of lead, tin, and other metal stabilizers. On
      the other hand, exposure to UV-radiation was seen to promote the migration of
      lead, tin, and other metal stabilizers. A lead concentration of about 0.8mg/l
      (ppm) was detected after 14 days of exposure to the UV-radiation.

PMID- 11240068
TI  - Evaluation of natural attenuation rate at a gasoline spill site.
AB  - Contamination of groundwater by gasoline and other petroleum-derived hydrocarbons
      released from underground storage tanks (USTs) is a serious and widespread
      environmental problem. Natural attenuation is a passive remedial approach that
      depends upon natural processes to degrade and dissipate contaminants in soil and
      groundwater. Currently, in situ column technique, microcosm, and computer
      modeling have been applied for the natural attenuation rate calculation. However,
      the subsurface heterogeneity reduces the applicability of these techniques. In
      this study, a mass flux approach was used to calculate the contaminant mass
      reduction and field-scale decay rate at a gasoline spill site. The mass flux
      technique is a simplified mass balance procedure, which is accomplished using the
      differences in total contaminant mass flux across two cross-sections of the
      contaminant plume. The mass flux calculation shows that up to 87% of the
      dissolved total benzene, toluene, ethylbenzene, and xylene (BTEX) isomers removal
      was observed via natural attenuation at this site. The efficiency of natural
      biodegradation was evaluated by the in situ tracer method, and the first-order
      decay model was applied for the natural attenuation/biodegradation rate
      calculation. Results reveal that natural biodegradation was the major cause of
      the BTEX mass reduction among the natural attenuation processes, and
      approximately 88% of the BTEX removal was due to the natural biodegradation
      process. The calculated total BTEX first-order attenuation and biodegradation
      rates were 0.036 and 0.025% per day, respectively. Results suggest that the
      natural attenuation mechanisms can effectively contain the plume, and the mass
      flux method is useful in assessing the occurrence and efficiency of the natural
      attenuation process.

PMID- 11240069
TI  - Impact of thermal treatment on metal in sewage sludge from the Psittalias
      wastewater treatment plant, Athens, Greece.
AB  - This paper describes a laboratory study that examined the effect of thermal
      treatment at four different temperatures on the behavior of heavy metals in the
      anaerobically treated primary sludge from the Psittalias wastewater treatment
      plant. The sewage sludge was found to contain significant amounts of heavy metals
      (Cr, Cu, Fe, Ni, Pb and Zn). The metal form distribution in the sludge samples
      which was determining by the application of a sequential extraction procedure
      revealed that a significant portion of metals was embodied in the organic and
      reducible fractions. Treatment at 105, 250, 650 and 900 degrees C demonstrated
      significant conversions of the metals to a less mobile form as well as removal by
      vaporization. By applying sequential analysis, it was found that most of the
      metals were removed from the initial mobile phases to more stable ones. Also,
      significant amounts were transformed to the gaseous phase.

PMID- 11240071
TI  - Moisture effect on the transport of organic vapors in sand.
AB  - Vapor-phase affects the transport, lifetime, and fate of volatile organic
      contaminants in soils. Furthermore, it has an effect on the assessment and the
      selection of a remediation approach. The diffusion of dichloromethane (DCM),
      1,1,1-trichloroethane (TCE) and carbon tetrachloride (CTC) in dry and wet sand
      media were investigated using a packed column at room temperature. The apparent
      diffusion coefficients, D(app), which accounts for effective diffusion and
      sorption of DCM, TCE and CTC were determined by fitting the experimental data to
      a diffusion model. The apparent diffusion coefficients of DCM, TCE and CTC for
      wet sand were found to be larger than the corresponding values for dry sand. The
      presence of water reduced retardation factors expressed in terms of the sorption
      capacity for each compound. The results indicated that dry mineral surface
      provided dominant sorption sites. This is reflected in greater amounts of organic
      vapors adsorbed under dry conditions. On the other hand, lower sorption
      capacities for organic compounds on vapor-water interface than on vapor-mineral
      interface and their low solubilities resulted in smaller retardation factors in
      wet sand. The experiments clearly demonstrate the role of humidity in sorption
      and transport of vapors in sand.

PMID- 11240070
TI  - Dechlorination of polychlorobiphenyls using NaBH(4) and NaBH(4)/LiCl at 120-310
      degrees C in glyme solvents.
AB  - High temperature PCB dechlorination (Aroclor 1016) occurred using NaBH(4) alone
      in tetraglyme at 290-310 degrees C within 2h in a sealed tube. Aroclor 1016
      dechlorination was also quantitatively achieved using NaBH(4)/LiCl/glyme solvents
      (di-, tri-, or tetraglyme) at 125-135 degrees C. The best results were obtained
      by prestirring NaBH(4), LiCl and the glyme solvent at room temperature before
      heating at 125-135 degrees C. At equivalent conditions, PCB dechlorination rates
      were found to depend on solvent in the order: tetraglyme>triglyme>diglyme. At 130
      degrees C, Aroclor 1016 can be dechlorinated in NaBH(4)/LiCl/tetraglyme in 4h. 2
      Chlorobiphenyl and 2,2'-dichlorobiphenyl were the least reactive congeners in
      dechlorinations with NaBH(4)/LiCl in diglyme. Competitive dechlorinations with
      NaBH(4)/LiCl in diglyme showed 3-chloro- and 4-chlorobiphenyl reacted faster than
      2-chlorobiphenyl at 130 degrees C. The reactions were clean with no solvent
      decomposition in the range of 120-162 degrees C.

PMID- 11240072
TI  - Animal models of cancer pain may reveal novel approaches to palliative care.

PMID- 11240073
TI  - The effect of genotype on sensitivity to electroacupuncture analgesia.
AB  - Individual differences in sensitivity to pain and analgesia are well appreciated,
      and increasing evidence has pointed towards a role of inherited genetic factors
      in explaining some proportion of such variability. It has long been known by
      practitioners of acupuncture, an ancient modality of analgesia, that some
      patients are 'responders' and others 'non-responders.' The present research was
      aimed at defining the inherited genetic influence on acupuncture analgesia in the
      mouse, using 10 common inbred strains. Two pairs of metallic needles were
      inserted into acupoints ST 36 and SP 6, fixed in situ and then connected to the
      output channel of an electric pulse generator. Electroacupuncture (EA) parameters
      were set as constant current output (intensity: 1.0-1.5-2.0 mA, 10 min each;
      frequency: 2 or 100 Hz) with alteration of a positive and negative square wave,
      0.3 ms in pulse width. Tail-flick latencies evoked by radiant heat were measured
      before, during and after EA stimulation. Narrow-sense heritability estimates of 2
      and 100 Hz EA were 0.37 and 0.16, respectively. We found that the C57BL/10 strain
      was the most sensitive, and the SM strain was the least sensitive to both 2 and
      100 Hz EA. However, the relative sensitivities of other strains to these two EA
      frequencies suggested some genetic dissociation between them as well. These
      results demonstrate a role of inherited genetic factors in EA sensitivity in the
      mouse, although the low-to-moderate heritability estimates suggest that
      environmental factors may be of greater importance in predicting who will benefit
      from this analgesic modality.

PMID- 11240074
TI  - Influences on the fusimotor-muscle spindle system from chemosensitive nerve
      endings in cervical facet joints in the cat: possible implications for whiplash
      induced disorders.
AB  - The aim of the present study was to establish if there exists reflex connections
      from ligamentous structures in cervical facet joints and the fusimotor system of
      dorsal neck muscles. In seven cats, anaesthetized with alpha-chloralose,
      bradykinin (BK) of concentrations between 12 and 50 microg was injected into the
      facet joint between C1 and C2. Recordings were made from single muscle spindle
      afferents (MSA) originating in contralateral trapezius and splenius muscles
      (TrSp). Fusimotor induced changes in the sensitivity of the muscle spindle
      afferents were assessed by recording the responses to sinusoidal stretches of the
      TrSp muscles. The mean rate of discharge and the depth of modulation of a fitted
      sine were taken as quantitative estimates of the response. A total of 25 MSAs
      were recorded, and 21 of these showed clear-cut alterations in their responses to
      the sinusoidal stretches following Bk. injections into contralateral facet joint.
      The majority of the responding afferents (13/21) showed changes in their
      responses indicating an increased activity of static fusimotoneurones, although
      responses of dynamic and mixed static and dynamic nature were also seen. Local
      anaesthetics applied to the intraarticular receptors abolished the effects.
      Injection (i.v.) of a general anaesthetic (pentobarbital) abolished the effects.
      The results show that there exist reflex connections between receptors in
      cervical facet joints and fusimotoneurones of dorsal neck muscles, and this might
      be of importance in the pathophysiology behind whiplash associated disorders
      (WAD).

PMID- 11240075
TI  - Treatment of severe pain from osteoarthritis with slow-release tramadol or
      dihydrocodeine in combination with NSAID's: a randomised study comparing
      analgesia, antinociception and gastrointestinal effects.
AB  - Opioids are increasingly used in the treatment of chronic non-malignant pain. The
      aim of this open-label, randomised, parallel group study was to compare analgesia
      and side-effects of two commonly used opioid analgesics, tramadol and
      dihydrocodeine, in long-acting formulations in 60 osteoarthritis patients with
      strong pain despite NSAID's. Dose titration based on effect was performed with
      the respective immediate release solutions given additionally to tramadol 100 mg
      bid and dihydrocodeine 60 mg bid during the first 4 days of the 1 month
      treatment. Electrical sensation and pain thresholds over the osteoarthritic joint
      and at a distant location and gastrointestinal transit times were performed
      before and during treatment. Thirty patients with pain controlled by NSAID's
      alone formed the comparator group. Pain intensities at rest and during movement
      decreased highly significantly with tramadol and dihydrocodeine from median pre
      treatment verbal ratings of over 3 (0=none, 4=unbearable) to 1 and below from the
      second treatment day onwards (ANOVA P<0.0001). Pain at rest was significantly
      lower with tramadol (ANOVA P=0.04), but ratings were similar during movement.
      Mean (95% CI) daily doses on days 1 and 28 were 209 (198-220) mg and 203 (191
      206) mg of tramadol, and 129 (122-136) mg and 130 (121-134) mg of dihydrocodeine,
      respectively. Minor side-effects were more common with tramadol (P=0.04). Changes
      in bowel functions and symptoms were minor with both treatments, but the
      frequency of defaecation was lower and stools were harder with dihydrocodeine.
      Orocaecal transit time remained unchanged and similar to controls with both
      analgesics. Colonic transit times only increased significantly during treatment
      with dihydrocodeine. Sensation and pain thresholds were lower pre-treatment in
      both groups than in controls and increased during treatment. These
      antinociceptive effects were more marked in the tramadol group and distant from
      the osteoarthritic joint. We conclude rapid pain relief was achieved with both
      long-acting tramadol and dihydrocodeine with NSAID's in strong osteoarthritis
      pain. Minimal dose titration was required and side-effects were minor. Tramadol
      interfered less with intestinal function and showed greater antinociceptive
      action.

PMID- 11240076
TI  - Opiate self-administration as a measure of chronic nociceptive pain in arthritic
      rats.
AB  - The study examined the validity of oral fentanyl self-administration (FSA) as a
      measure of the chronic nociceptive pain that develops in rats with adjuvant
      arthritis independently of acute noxious challenges. Arthritic rats self
      administered more of a 0.008 mg/ml fentanyl solution (up to 3.4 g/rat per day)
      than non-arthritic controls (0.5 g/rat per day) and did so with a biphasic time
      course that reached peak during weeks 3 and 4 after inoculation with
      Mycobacterium butyricum. The time course paralleled both the disease process and
      the chronic pain. Continuous infusion of dexamethasone during weeks 3 and 4 via
      subcutaneous osmotic pumps at 0.0025-0.04 mg/rat per day disrupted the arthritic
      disease and decreased FSA to a level (i.e. by 65%) similar to that observed in
      non-arthritic rats. Continuous naloxone (2.5 mg/rat per day) decreased FSA (by
      55%) in arthritic but not in non-arthritic animals. Continuous, subcutaneous
      infusion of fentanyl also decreased arthritic FSA in a manner that varied with
      dose at 0.04-0.16 mg/rat per day doses, but leveled off at 47% of controls with
      0.31 mg/rat per day. The effects of continuous fentanyl on arthritic FSA occurred
      only with those doses and dose-dependent dynamics with which fentanyl also
      induced dependence in non-arthritic rats. The findings indicate that pain, rather
      than the rewarding or dependence-inducing action of fentanyl mediates FSA in
      arthritic rats. Paralleling patient-controlled analgesic drug intake, FSA offers
      a specific measure allowing the dynamic effects of neurobiological agents to be
      studied in this unique animal model of persistent nociceptive pain.

PMID- 11240077
TI  - Work injury management of refractory low back pain: relations with ethnicity,
      legal representation and diagnosis.
AB  - While psychosocial factors are known to influence treatment outcomes in low back
      pain patients, relatively little is known about how they may influence work
      injury management of low back pain. This study examined medical and psychosocial
      factors associated with work injury management decisions relative to patients
      with occupational low back pain. A retrospective review of 132 patients who had
      settled their injury claims showed that two psychosocial factors, ethnicity and
      litigation status, were associated with work injury management. Temporary total
      disability costs and impairment ratings were lower for African Americans than for
      Caucasians, but only in the absence of legal representation. Similarly, patients
      with specific pathology underwent more treatment, especially diagnostic testing,
      than patients with non-specific back pain, but only in the presence of legal
      representation. Having evidence of a specific lesion and legal representation
      were also associated with claimants' final disability ratings. Results are
      discussed in terms of a model of social judgment in which properties of the
      judge, target, and context influence judgments. Implications for work injury
      management and disability determination, as well as future research are
      discussed.

PMID- 11240078
TI  - Habituation of the early pain-specific respiratory response in sustained pain.
AB  - Neurokinin-1 receptor and mu-opioid receptor agonists affect respiratory rhythm
      when injected directly into the preBotzinger brainstem complex, which is the
      hypothesized site for respiratory rhythmogenesis in mammals (Science 286 (1999)
      1566). Early stress-induced analgesia (SIA) is naloxone-insensitive and as such
      considered independent of the activation of the mu-opioid system. Prolonged
      application of electrical shocks, however, produces analgesia that is mediated by
      the mu-opioid system (Science 208 (1980) 623). Together these findings suggest
      that any early pain-specific increased respiration should be attenuated in the
      tonic state of pain. Ten healthy, pain-free female volunteer subjects
      participated in this experimental study involving deep acute and tonic pain. The
      experimental design included three conditions: (1) baseline; (2) pain; and (3) a
      placebo control stimulus. Experimental pain was induced by the infusion of
      hypertonic saline into the masseter muscle. Infusion of isotonic saline in the
      contralateral masseter was used as a control. Blinded subjects were randomly
      assigned to a particular sequential order of the experimental stages, i.e.
      hypertonic saline infusion preceded the isotonic saline infusion or vice versa.
      Respiration rate, mean peak inspiratory and expiratory flow rates, and the minute
      ventilation volume quantified breathing. Results indicate that effects on
      respiration were pain-specific and that the early effects on respiration were
      significantly attenuated in sustained pain. In the early stage of pain, all
      monitored variables (respiration rate, minute ventilation volume, and inspiratory
      and expiratory flow rates) were elevated to statistically significant degrees
      when compared to measurements taken at baseline or during control infusion. Only
      respiration rate continued to be significantly elevated in sustained pain. We
      concluded that rhythmogenic neurons in the preBotzinger brainstem complex appear
      as the likely target for pro-nociceptive and anti-nociceptive input, explaining
      both the observed initial facilitation and subsequent habituation of respiration
      in early and sustained pain.

PMID- 11240079
TI  - A randomized controlled component analysis of a behavioral medicine
      rehabilitation program for chronic spinal pain: are the effects dependent on
      gender?
AB  - The aim of the present study was to evaluate the outcome of a behavioral medicine
      (BM) rehabilitation program and the outcome of its two main components, compared
      to a 'treatment-as-usual' control group (CG). The study employed a 4x4 repeated
      measures design with four groups and four assessment periods (pre-treatment, post
      treatment, 6-month follow-up, and 18-month follow-up). The group studied
      consisted of subjects on sick leave identified in a nationwide health insurance
      scheme in Sweden. After inclusion, the subjects were randomized to one of four
      conditions, which were: (1) behavior-oriented physical therapy (PT); (2)
      cognitive behavioral therapy (CBT); (3) BM rehabilitation consisting of PT+CBT
      (BM); (4) a 'treatment-as-usual' CG. The treatments were given over a period of 4
      weeks, PT and CBT on a part-time basis and BM on a full-time basis. Outcome
      variables were sick leave, early retirement, and health-related quality of life
      (measured using the Short Form Health Survey, SF-36). The results showed that the
      risk of being granted full-time early retirement was significantly lower for
      females in PT and CBT compared to the CG during the 18-month follow-up period.
      However, the total absence from work (sick listing plus early retirement) in days
      over the 18-month follow-up period was not significantly different in the CG
      compared to the treatments. On the SF-36, women in CBT and BM reported a
      significantly better health-related quality of life than women in the CG at the
      18-month follow-up. No significant differences for men were found on the SF-36
      scales. In conclusion, the results revealed gender differences in the outcome of
      the treatments and that the components of this BM program yielded as good results
      as the whole program.

PMID- 11240080
TI  - Spiritual healing as a therapy for chronic pain: a randomized, clinical trial.
AB  - Spiritual healing is a popular complementary and alternative therapy; in the UK
      almost 13000 members are registered in nine separate healing organisations. The
      present randomized clinical trial was designed to investigate the efficacy of
      healing in the treatment of chronic pain. One hundred and twenty patients
      suffering from chronic pain, predominantly of neuropathic and nociceptive origin
      resistant to conventional treatments, were recruited from a Pain Management
      Clinic. The trial had two parts: face-to-face healing or simulated face-to-face
      healing for 30 min per week for 8 weeks (part I); and distant healing or no
      healing for 30 min per week for 8 weeks (part II). The McGill Pain Questionnaire
      was pre-defined as the primary outcome measure, and sample size was calculated to
      detect a difference of 8 units on the total pain rating index of this instrument
      after 8 weeks of healing. VASs for pain, SF36, HAD scale, MYMOP and patient
      subjective experiences at week 8 were employed as secondary outcome measures.
      Data from all patients who reached the pre-defined mid-point of 4 weeks (50
      subjects in part I and 55 subjects in part II) were included in the analysis. Two
      baseline measurements of outcome measures were made, 3 weeks apart, and no
      significant differences were observed between them. After eight sessions there
      were significant decreases from baseline in McGill Pain Questionnaire total pain
      rating index score for both groups in part I and for the control group in part
      II. However, there were no statistically significant differences between healing
      and control groups in either part. In part I the primary outcome measure
      decreased from 32.8 (95% CI 28.5-37.0) to 23.3 (16.8-29.7) in the healing group
      and from 33.1 (27.2-38.9) to 26.1 (19.3-32.9) in the simulated healing group. In
      part II it changed from 29.6 (24.8-34.4) to 24.0 (18.7-29.4) in the distant
      healing group and from 31.0 (25.8-36.2) to 21.0 (15.7-26.2) in the no healing
      group. Subjects in healing groups in both parts I and II reported significantly
      more 'unusual experiences' during the sessions, but the clinical relevance of
      this is unclear. It was concluded that a specific effect of face-to-face or
      distant healing on chronic pain could not be demonstrated over eight treatment
      sessions in these patients.

PMID- 11240081
TI  - Selective attentional bias for pain-related stimuli amongst pain fearful
      individuals.
AB  - Recent research indicates that people who are fearful of pain tend to report more
      negative pain experiences. It also seems that attentional mechanisms may be
      particularly important in the perception of painful stimuli, especially amongst
      pain fearful individuals. Drawing on a paradigm used to examine biased cognitive
      processes in the emotional disorders, the current study investigated whether the
      fear of pain would be related to a greater selective attentional bias in favour
      of pain-related stimuli. In order to determine the nature of this bias, stimuli
      material were varied in terms of whether they were related to pain sensations,
      were related to socially threatening situations or were relatively positive.
      Those with a high fear of pain exhibited a selective attentional bias towards
      pain-related information, compared to those classified as low in the fear of
      pain. No group differences were found for either social threat or positive
      stimuli. These results indicate that one reason why those with a high fear of
      pain are particularly susceptible to negative pain experiences could be due to
      biased attentional processes. Suggestions for cognitive interventions designed to
      reduce such biases are discussed, as are directions for future research.

PMID- 11240082
TI  - Comparison of the effects of MK-801, ketamine and memantine on responses of
      spinal dorsal horn neurones in a rat model of mononeuropathy.
AB  - Selective ligation of the L5/L6 spinal nerves produces a partial denervation of
      the hindpaw and has proved to be a useful model for studying the mechanisms
      underlying neuropathic pain. Two weeks after surgery, in vivo
      electrophysiological studies were performed in sham operated and nerve injured
      rats and the responses of spinal dorsal horn neurones to controlled electrical
      and natural (mechanical and heat) stimuli were recorded. The systemic effects of
      three N-methyl-D-aspartate receptor (NMDA) antagonists, ketamine (1-10 mg/kg),
      memantine (1-20 mg/kg) and MK-801 (0.1-5 mg/kg) were compared. Ketamine a
      clinically available NMDA receptor antagonist, produced greater reductions of the
      postdischarge, thermal (10 mg/kg, P=0.02), and mechanical evoked responses in
      spinal nerve ligated (SNL) rats (von Frey 9 g, 1 mg/kg, P=0.04; 5 mg/kg, P=0.01;
      10 mg/kg, P=0.05; von Frey 50 g, 5 mg/kg, P=0.02; 10 mg/kg, P=0.003). The
      inhibition of wind-up was comparable in both animal groups. Memantine produced
      powerful inhibitions of wind-up after nerve injury with little effect in sham
      controls (5 mg/kg, P=0.02). The postdischarge, mechanical and thermal evoked
      responses were reduced to similar extents by memantine in both experimental
      groups. The effects of MK-801 were comparable between SNL and sham operated rats
      for all neuronal measures (wind-up, postdischarge, thermal and noxious mechanical
      evoked responses). The differential blocking abilities of these antagonists on
      the various neuronal responses may relate to the characteristics of their voltage
      dependent blockage of the channel associated with the receptor. The favourable
      side effect profile of memantine supports its potential use for the treatment of
      neuropathic pain.

PMID- 11240083
TI  - Neuropeptide Y in trigeminal ganglion following chronic constriction injury of
      the rat infraorbital nerve: is there correlation to somatosensory parameters?
AB  - The aim of this study was to investigate neuropeptide Y (NPY) levels in
      trigeminal ganglia following infraorbital nerve injury. Two experimental
      procedures were performed in three groups of rats: a unilateral chronic
      constriction injury (CCI) to the infraorbital nerve (n=13), nerve manipulation
      without CCI (n=13) and unoperated controls (n=8). All rats underwent baseline and
      regular assessment of mechanical withdrawal threshold (Von Frey) and reaction to
      pin prick as well as free behavior evaluations. CCI to the infraorbital nerve
      induced significant hyperalgesia and allodynia within 9-12 days. At 6 days seven
      rats were euthanized and trigeminal ganglia harvested for immunocytochemical
      (ICC) studies. The study was ended at 14 days when all rats were euthanized and
      their ganglia harvested for ICC and radioimmunoassay (RIA) studies. An increase
      in NPY levels was seen in the ipsilateral ganglia of manipulated and CCI rats at
      6 days, when rats displayed no pain-related behavior. At 14 days, ICC and RIA
      both detected significant increases in NPY levels in the ipsilateral ganglia of
      CCI and manipulated rats but not in unoperated controls. The possible roles of
      NPY in pain modulation and nerve injury are discussed in light of these findings.

PMID- 11240084
TI  - Breakthrough cancer pain: a randomized trial comparing oral transmucosal fentanyl
      citrate (OTFC) and morphine sulfate immediate release (MSIR).
AB  - Oral transmucosal fentanyl citrate (OTFC); Actiq) is a drug delivery formulation
      used for management of breakthrough cancer pain. Previous studies with open-label
      comparisons indicated OTFC was more effective than patients' usual opioid for
      breakthrough pain. The objective of this study was to compare OTFC and morphine
      sulfate immediate release (MSIR) for management of breakthrough pain in patients
      receiving a fixed scheduled opioid regimen. This double-blind, double-dummy,
      randomized, multiple crossover study was conducted at 19 US university- and
      community-based hospitals and clinics and comprised 134 adult ambulatory cancer
      patients. Patients were receiving a fixed scheduled opioid regimen equivalent to
      60-1000 mg/day oral morphine or 50-300 microg/h transdermal fentanyl, were using
      a 'successful' MSIR dose (15-60 mg) as defined by entry criteria, and were
      experiencing 1-4 episodes of breakthrough pain per day. In open-label fashion,
      OTFC was titrated such that a single unit (200-1600 microg) provided adequate
      pain relief with acceptable side effects. Successfully titrated patients entered
      the double-blind phase of the study and received ten prenumbered sets of
      randomized capsules and oral transmucosal units. Five sets were the successful
      OTFC dose paired with placebo capsules, and five sets were placebo OTFC paired
      with capsules containing the successful MSIR dose. Patients took one set of study
      medication for each episode of target breakthrough pain. Pain intensity (PI),
      pain relief (PR) and global performance of medication (GP) scores were recorded.
      Pain intensity differences (PID) were calculated and 15-min PID was the primary
      efficacy variable. Adverse events were recorded. Sixty-nine percent of patients
      (93/134) found a successful dose of OTFC. OTFC yielded outcomes (PI, PID, and PR)
      at all time points that were significantly better than MSIR. GP also favored OTFC
      and more patients opted to continue with OTFC than MSIR following the study.
      Somnolence, nausea, constipation, and dizziness were the most common drug
      associated side effects. In conclusion, OTFC was more effective than MSIR in
      treating breakthrough cancer pain.

PMID- 11240085
TI  - The antinociceptive effect of intrathecal administration of epibatidine with
      clonidine or neostigmine in the formalin test in rats.
AB  - The analgesic effect of intrathecal injection of epibatidine, clonidine and
      neostigmine, compounds that elevate ACh, was examined in the formalin test, a
      model of post-injury central sensitization in the rat. The compounds were
      injected alone and in combination. Intrathecal injection of epibatidine alone did
      not alter pain behaviors, compared to vehicle-treated rats. Intrathecal injection
      of clonidine dose-dependently reduced tonic pain behaviors (ED(50)+/-95%
      confidence limits=6.7+/-4.8 microg). The combination of clonidine and epibatidine
      (C:E), in the ratio of 26:1, dose-dependently reduced tonic pain behaviors; and
      the ED(50) of C:E was 1.1+/-0.98 microg a significant 6-fold leftward shift of
      the dose response curve, compared with clonidine alone. The antinociceptive
      effect of C:E (26:1) was attenuated by pre-treatment with the nAChR antagonist
      mecamylamine. Neostigmine dose-dependently reduced tonic pain behaviors
      (ED(50)=1.5+/-1.3 microg). The combination of neostigmine and epibatidine, in a
      ratio of 8:1, significantly shifted the dose response curve 4-fold to the left
      (ED(50)=0.4+/-0.3 microg). The effect is mediated in part by the activation of
      the nAChR and possibly by the enhanced release of ACh. These data demonstrate
      significant enhancement of the antinociceptive effects of spinally delivered
      analgesics by a nAChR agonist, suggesting that this class of compounds may have
      utility as adjuvants when combined with conventional therapeutics.

PMID- 11240086
TI  - Morphine-induced spinal cholinergic activation: in vivo imaging with positron
      emission tomography.
AB  - Positron emission tomography (PET) imaging of spinal cord in monkeys with a
      cholinergic tracer demonstrates increased spinal cholinergic activity in response
      to an analgesic dose of morphine, and this PET result correlates with measurement
      of acetylcholine spillover into spinal cord extracellular space induced by
      morphine, as measured by microdialysis. Previous studies in rats, mice, and sheep
      demonstrate activation of spinal cholinergic neurons by systemic opioid
      administration, and participation of this cholinergic activity in opioid-induced
      analgesia. Testing the relevance of this observation in humans has been limited
      to measurement of acetylcholine spillover into lumbar cerebrospinal fluid. The
      purpose of this study was to apply a recently developed method to image spinal
      cholinergic terminals non-invasively via PET and to test the hypothesis that the
      tracer utilized would reflect changes in local cholinergic activity. Following
      Animal Care and Use Committee approval, seven adult male rhesus monkeys were
      anesthetized on three separate occasions. On two of the occasions PET scans were
      performed using [(18)F] (+)-4-fluorobenzyltrozamicol ([(18)F]FBT), which
      selectively binds to the vesicular acetylcholine (ACh) transporter in the
      presynaptic cholinergic terminals. PET scans were preceded by injection of either
      saline or an analgesic dose of IV morphine (10 mg/kg). On the third occasion,
      microdialysis catheters were inserted in the spinal cord dorsal horn and
      acetylcholine concentrations in dialysates determined before and after IV
      morphine injection. Morphine increased cholinergic activity in the spinal cord,
      as determined by blood flow corrected distribution volume of [(18)F]FBT in the
      cervical cord compared to the cerebellum. Morphine also increased acetylcholine
      concentrations in microdialysates from the cervical cord dorsal horn. The one
      animal which did not show increased spinal cholinergic activity by PET from this
      dose of morphine also did not show increased acetylcholine from this morphine
      dose in the microdialysis experiment. These data confirm the ability to use PET
      to image spinal cholinergic terminals in the monkey spinal cord and suggest that
      acute changes in cholinergic activity can be imaged with this non-invasive
      technique. Following preclinical screening, PET scanning with [(18)F]FBT may be
      useful to investigate mechanisms of analgesic action in normal humans and in
      those with pain.

PMID- 11240087
TI  - Catastrophizing, depression and expectancies for pain and emotional distress.
AB  - The present research addressed the relation between catastrophizing, depression
      and response expectancies in anticipation of an experimental pain procedure. One
      hundred and twenty undergraduates (48 men, 72 women) participated in exchange for
      course credit. Prior to immersing one arm in a container of ice water,
      participants were asked to complete measures of catastrophizing and depression,
      and to estimate the degree of pain and emotional distress they expected to
      experience. After a 1-min immersion, participants rated their actual experience.
      Pain expectancies partially mediated the relation between catastrophizing and
      pain experience. Pain expectancies also mediated the relation between depression
      and pain experience. Catastrophizing, but not depression, was associated with a
      tendency to underestimate pain and emotional distress. The implications of these
      findings for the conceptual distinctiveness of catastrophizing and depression are
      discussed. Discussion also examines the potential implications of the present
      findings for pain management interventions.

PMID- 11240088
TI  - A cognitive-behavioral return-to-work program: effects on pain patients with a
      history of long-term versus short-term sick leave.
AB  - A cognitive-behavioral return-to-work focused program was evaluated in a
      randomized controlled design, and the effects were compared between two groups of
      women with musculoskeletal pain. One group of patients (n=36) had a history of
      long-term sick leave (>12 months) at the start of the program and the other
      (n=36) had a history of short-term sick leave (2-6 months). The outpatient
      treatment program, conducted by a psychologist, included 12 sessions with the
      primary aim to help the patients return-to-work. The treatment first included
      teaching of coping strategies such as applied relaxation, stress management,
      graded activity training and pacing. Thereafter the patients were taught how to
      manage difficulties at their return-to-work and how to generalize coping
      strategies to different risk factors at their work places. The control condition
      received treatment-as-usual. The results showed that the cognitive-behavioral
      return-to-work program was more effective than the treatment-as-usual control
      condition in reducing the number of days on sick leave for patients on short-term
      sick leave, but not for patients on long-term sick leave. The treatment program
      also helped the patients on short-term sick leave to increase their ability to
      control and decrease pain and to increase their general activity level compared
      to the control condition. These results underscore the need for an early return
      to-work focused rehabilitation to prevent long-term sick leave and disability.

PMID- 11240089
TI  - Abnormal sensitization and temporal summation of second pain (wind-up) in
      patients with fibromyalgia syndrome.
AB  - Although individuals with fibromyalgia syndrome (FMS) consistently report wide
      spread pain, clear evidence of structural abnormalities or other sources of
      chronic stimulation of pain afferents in the involved body areas is lacking.
      Without convincing evidence for peripheral tissue abnormalities in FMS patients,
      it seems likely that a central pathophysiological process is at least partly
      responsible for FMS, as is the case for many chronic pain conditions. Therefore,
      the present study sought to obtain psychophysical evidence for the possibility
      that input to central nociceptive pathways is abnormally processed in individuals
      with long standing FMS. In particular, temporal summation of pain (wind-up) was
      assessed, using series of repetitive thermal stimulation of the glabrous skin of
      the hands. Although wind-up was evoked both in control and FMS subjects, clear
      differences were observed. The perceived magnitude of the sensory response to the
      first stimulus within a series was greater for FMS subjects compared to controls,
      as was the amount of temporal summation within a series. Within series of
      stimuli, FMS subjects reported increases in sensory magnitude to painful levels
      for interstimulus intervals of 2-5 s, but pain was evoked infrequently at
      intervals greater than 2 s for control subjects. Following the last stimulus in a
      series, after-sensations were greater in magnitude, lasted longer and were more
      frequently painful in FMS subjects. These results have multiple implications for
      the general characterization of pain in FMS and for an understanding of the
      underlying pathophysiological basis.

PMID- 11240090
TI  - Concentration-effect relationship of intravenous alfentanil and ketamine on
      peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic
      pain.
AB  - Both mu opioid agonists and N-methyl-D-aspartate (NMDA) receptor antagonists are
      implicated in the regulation of neuropathic pain in post-nerve injury preclinical
      pain models. This study characterizes the effects of intravenously infused
      alfentanil (a mu-receptor agonist) and ketamine (an NMDA-receptor antagonist) on
      human neuropathic pain states, characterized by allodynia and hyperalgesia. Using
      diphenhydramine as the placebo, alfentanil and ketamine infusions were given in a
      randomized double-blind fashion 1 week apart via a computer-controlled infusion
      (CCI) pump that was programmed to target plasma levels of alfentanil at 25, 50
      and 75 ng/ml and ketamine at 50, 100 and 150 ng/ml. At the beginning of each
      infusion and each targeted plasma level, baseline vital signs, neurosensory
      testing that included thermal thresholds, thermal pain and von Frey filament
      thresholds, and spontaneous and evoked pain scores were obtained. Moreover, the
      areas of allodynia or hyperalgesia to stroking and a 5.18 von Frey filament were
      mapped at the beginning and the end of each infusion. A total of seven males and
      five females with post-nerve injury allodynia and hyperalgesia were enrolled in
      the study. Elevations of cold, warm, hot pain and von Frey tactile thresholds
      were noted. Dose-dependent increases in cold and cold pain thresholds, and
      reductions in stroking pain scores were noted in both the alfentanil and the
      ketamine infusions. In addition, alfentanil showed a statistically significant
      dose-dependent reduction in both spontaneous and von Frey pain scores. Both the
      alfentanil and ketamine infusions showed a reduction in the stroking hyperalgesic
      area and ketamine showed a significant reduction in the von Frey hyperalgesia
      area. No significant CNS side effects and changes in vital signs were noted. A
      partial deafferentation state was found in the post-nerve injury patients who
      presented with allodynia and hyperalgesia. The effects of alfentanil on cold and
      cold pain thresholds and spontaneous pain scores correlates with previous studies
      suggesting an opiate central analgesic effect. In addition, the reduction of the
      hyperalgesic area and evoked pain scores with the alfentanil infusion suggests
      that opioids may have some peripheral effects in the post-nerve injury patients.
      Therefore, clinical utilization of opioids with careful titration may be
      beneficial in post-nerve injury patients with partial deafferentation. With the
      absence of significant CNS side effects, the ketamine infusion not only
      demonstrated the well-documented spinal cord mechanism of the NMDA receptor, but
      the result of the current study also suggests that a peripheral mechanism of NMDA
      receptor may exist. The relationship between central sensitization and regulation
      of peripheral NMDA-receptor expression requires further investigation.

PMID- 11240091
TI  - Seeking a simple measure of analgesia for mega-trials: is a single global
      assessment good enough?
AB  - We sought to investigate the potential of using a simple global estimation ('How
      effective do you think the treatment was?') as a measure of efficacy by comparing
      it with at least 50%maxTOTPAR (at least 50% of the maximum possible pain relief)
      in acute pain studies. One hundred and fifty randomized, double-blind trials
      included in 11 systematic reviews of single dose, oral analgesics for
      postoperative pain were used as a source of data. The relationship between the
      proportion of patients reporting the top two or three values on a five-point
      global scale and the proportion with at least 50%maxTOTPAR was investigated.
      Twenty-six trials provided data on the proportion reporting the top two
      categories (very good or excellent) and 27 gave data on the top three categories
      (good, very good or excellent). The relationship between the percentage of
      patients recording the top two categories on a five-point global scale and the
      proportion with at least 50%maxTOTPAR was fair (r(2)=0.67). That for the top
      three categories was less good (r(2)=0.57). Similar numbers-needed-to-treat were
      calculated for aspirin 600/650 mg and ibuprofen 400 mg using at least
      50%maxTOTPAR and the top two categories. No real difference was seen in the
      correlation for standard wording compared to non-standard wording. Individual
      patient data were also used from four randomized, placebo-controlled, double
      blind trials in postoperative pain. The frequency distribution for %maxTOTPAR was
      plotted for patients reporting each of the five categories on the global scale. A
      global assessment provides similar measures of analgesic efficacy as TOTPAR
      derived from hourly measurements, but the effects of adverse effects have yet to
      be understood.

PMID- 11240092
TI  - International harmonisation of anthelmintic efficacy guidelines.
AB  - The "International Co-operation on Harmonisation of Technical Requirements for
      Registration of Veterinary Medicinal Products (VICH)" is an international
      programme of co-operation between regulatory authorities and the animal health
      industries of the European Union, Japan, and the United States of America which
      aims to harmonise the technical requirements for the registration of veterinary
      medicinal products. Australia and New Zealand participate as active observers.
      The objective of the present paper is to present the guidelines established by
      the working group on Anthelmintic Efficacy Guidelines: (1) efficacy of
      anthelmintics: general requirements (VICH GL7); (2) efficacy of anthelmintics:
      specific recommendations for bovines (VICH GL12); (3) efficacy of anthelmintics:
      specific recommendations for ovines (VICH GL13); (4) efficacy of anthelmintics:
      specific recommendations for caprines (VICH GL14). These guidelines do not
      consist of rigid stipulations, but make clear recommendations on the minimal
      standards needed. To the veterinary profession, livestock producers and animal
      owners, harmonisation should mean quicker access to safer and more effective
      veterinary anthelmintics. In general, products should be relatively more
      affordable because of the reduction in registration costs and efficient use of
      resources by the regulatory authorities.

PMID- 11240093
TI  - The effect of the ovine host parasitaemia on the development of Babesia ovis
      (Babes, 1892) in the tick Rhipicephalus bursa (Canestrini and Fanzago, 1877).
AB  - Batches of Rhipicephalus bursa adult ticks were fed on two lambs with 10.0%
      (batch 1) and 0.3% (batch 2) Babesia ovis parasitaemia, respectively. Haemolymph
      and eggs were checked for parasites daily after detachment, before and after
      appearance of B. ovis in the lamb's blood.B. ovis kinetes were found in the
      haemolymph and eggs earlier in the engorged ticks detached before appearance of
      the parasite in the host blood. Rates of haemolymph and egg infection with B.
      ovis as well as the percentage of infected eggs were much higher in batch 1 (10%
      lamb parasitaemia) than in batch 2 ticks (0.3% lamb parasitaemia). In eggs
      incubated at 28 degrees C the optimal period to look for kinetes seems to be days
      4-9. Heavily infected ticks laid fewer less eggs within a shorter oviposition
      period. Pre-oviposition, pre-hatching periods and egg hatchability were not
      affected. Various parasitic forms are described in the haemolymph and the eggs.

PMID- 11240094
TI  - Canine visceral leishmaniosis: a remarkable histopathological picture of one case
      reported from Brazil.
AB  - This report describes a remarkable histopathological presentation of a
      symptomatic dog naturally infected with Leishmania (Leishmania) chagasi from
      Brazil. An intense inflammatory granulomatous reaction was observed in the liver
      and spleen associated with hypertrophy and hyperplasia of the mononuclear system
      (the classical histopathological picture of the disease). In addition, a spectrum
      of vascular lesions was observed in many organs. However, we did not find
      parasites (amastigotes of Leishmania) in any skin fragments of the ear, nose and
      or abdominal tissue. In fact, this animal had severe clinical signs, showed
      parasites in many organs, but no parasites in the skin. It appears that the
      presence or absence of parasites in the skin is not a good indicator of parasites
      in other organs or vice versa.

PMID- 11240096
TI  - Effects of previous suppressive anthelmintic treatments on subsequent nematode
      infection in fattening cattle in Argentina.
AB  - The effect of previous suppressive anthelmintic treatments after weaning on
      parasitological parameters and weight gain of cattle was studied in the Pampeana
      region of Argentina. The study was carried out at two grazing fattening periods:
      April 1995/July 1996 and April 1997/July 1998. During both periods, 60 weaned
      calves that grazed contaminated pastures, were divided into three groups during
      the first part of the periods: GY1 group was treated every 2 weeks with
      doramectin while GY2 and GY3 groups remained untreated. During the second part of
      the periods, from October onwards GY1 and GY2 remained untreated and GY3 was
      treated every 2 weeks. In this second period two new groups of 20 weaning young
      calves were added: TG (treated every 2 weeks) and UG (untreated). Egg counts
      (EPG), larval cultures, pasture larval counts, serum pepsinogen (Pep) and live
      weight gain (LWG) were recorded monthly. Ostertagia, Cooperia, Trichostrongylus
      and Haemonchus were the predominant genera. Despite low levels of previous
      infection during the first part of the period, slight differences of EPG between
      GY1 (P<0.09) or UG (P<0.05) and GY2 were detected in the second part of the
      fattening period in 1995/1996. In 1997/1998 moderate infection levels during the
      first part of the period were observed. During the second part of this period,
      GY1 and UG showed higher (P<0.001) EPG than GY2, and only GY3 and TG had (P<0.05)
      lower Pep levels. Also, during the second part of 1997/1998, LWG responses of GY3
      were higher (P<0.001) than those of GY1 and GY2. Live weight gain of GY2 exceeded
      GY1 by 10.7kg (P<0.006). Higher EPG and lower LWG of GY1 suggest that suppressive
      treatments negatively affected the level of resistance to infection of yearlings,
      but these effects were influenced by previous levels of nematode infection. The
      lack of differences between yearling (GY1) and calves (UG) groups suggest that,
      under the conditions of this study, there was no evidence that resistance to
      infection and the related parameters are influenced by the age.

PMID- 11240095
TI  - Specific IgA antibody response to coproantigens of Cryptosporidium parvum in
      serum and saliva of calves after experimental infection.
AB  - The antibody response to coproantigens of Cryptosporidium parvum was examined in
      saliva and sera of calves experimentally infected with C. parvum. Coproantigens
      of C. parvum with approximate molecular masses of 17, 15 and less than 14kDa were
      found in the feces of infected calves on day 3 or later, and 60 and 23kDa
      coproantigens observed between days 4 and 9 post-infection, respectively. The
      antibody reactivity to the coproantigens was mainly attributable to IgA class
      antibodies in saliva and was detectable during the convalescent phase of
      infection. A 15kDa protein isolated from the feces of infected calves by
      immunoaffinity adsorption using a monoclonal anti C. parvum antibody was
      recognized by IgA antibodies present in the saliva during the convalescent phase
      of infection. These results suggest that this coproantigen may be released from
      C. parvum sporozoites and may induce IgA antibody production in the mucosal
      immune system of infected calves.

PMID- 11240097
TI  - Diagnosis of psoroptic sheep scab with an improved enzyme-linked immunosorbent
      assay.
AB  - An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of
      specific antibodies against crude Psoroptes antigen. The diagnostic sensitivity
      was 93.7% in 191 sheep with clinical signs associated with mange. These animals
      originated from 29 flocks in which psoroptic mites were detected. All of 59 sheep
      infested with Psoroptes ovis were seropositive. Additionally, in 49% of 70
      clinically unaffected sheep originating from P. ovis-infested flocks, specific
      antibodies could be detected, suggesting that asymptomatic infestations can be
      diagnosed by serology. The specificity of the ELISA was 96.5% as determined with
      254 sheep originating from 44 flocks without clinical mange. Cross-reactivity in
      a low range was detected with selected sera of sheep with clinical chorioptic or
      forage mite infestations. Four sheep seroconverted 2 weeks after experimental P.
      ovis infestation, i.e. 2 weeks before clinical signs became obvious. After
      successful doramectin treatment of 14 sheep with naturally acquired P. ovis
      infestation, the ELISA values declined slowly but remained positive in seven
      cases beyond 17 weeks.

PMID- 11240098
TI  - Horn fly (Diptera: Muscidae) resistance to organophosphate insecticides.
AB  - Insecticidal ear tags impregnated with organophosphate (OP) insecticides were
      used each year from 1989 to 1998 at Rosepine, LA. Weekly fly counts were
      conducted to evaluate control efficacy of the treatments, and bioassays were
      conducted at least twice per year to measure fly susceptibility to OP and
      pyrethroid insecticides. Between 1989 and 1992, the efficacy of 20% diazinon
      impregnated ear tags was reduced from >20 to just 1 week of control. A high risk
      of control failure was observed when a resistance frequency of approximately 5%
      was measured in pre-season bioassays. Resistance to diazinon, fenthion, ethion,
      pirimiphos-methyl, and tetrachlorvinphos was observed. Esterase activity toward
      alpha-naphthyl acetate was significantly higher in flies collected at Rosepine in
      1997 than in flies from a laboratory colony and from a susceptible field
      population.

PMID- 11240099
TI  - Modelling the effect of surveillance programmes on spread of bovine herpesvirus 1
      between certified cattle herds.
AB  - For the eradication of an infectious agent, like bovine herpesvirus 1 (BHV-1),
      surveillance and certification can be used to reduce the transmission between
      herds. The goal of surveillance is that a certified herd that becomes infected is
      detected timely so that infection of several other certified herds is prevented.
      What counts is whether the reproduction ratio R, i.e. the average number of
      certified herds infected by one infected certified herd can be kept below 1. To
      support policy makers in making decisions about the minimal demands for a
      surveillance programme in an eradication campaign of BHV-1 in cattle, two
      mathematical models were investigated. With these models, the basic reproduction
      ratio between herds was calculated. The surveillance programmes were
      characterised with sample size, sampling frequency, test sensitivity, herd size,
      vaccination status, and contacts between herds. When R between herds is below 1,
      then the surveillance programme is sufficiently good to prevent spread of
      infection, provided that R is estimated well. In the model based on bulk milk
      testing sample size was replaced by a threshold at which bulk milk can be found
      positive. The R between herds was mainly influenced by the vaccination status,
      sampling frequency, and contacts between herds. Herd size moderately affected the
      outcome. Test sensitivity and sample size, however, were of minor importance. If
      herds of 50 cows became free of BHV-1 without vaccination, then spread of
      infection between herds might be prevented when animals within herds are sampled
      once a year (milk or blood samples). This frequency needs to be intensified,
      being twice a year, for larger herds and/or herds with extensive contacts with
      other herds. When bulk milk is sampled instead, sampling should be done at least
      every 5 months and more intensively, being each month, with larger herd sizes and
      more contacts between herds.

PMID- 11240100
TI  - In vitro evidence for a bacterial pathogenesis of equine laminitis.
AB  - Utilizing an in vitro laminitis explant model, we have investigated how bacterial
      broth cultures and purified bacterial proteases activate matrix
      metalloproteinases (MMPs) and alter structural integrity of cultured equine
      lamellar hoof explants. Four Gram-positive Streptococcus spp. and three Gram
      negative bacteria all induced a dose-dependent activation of MMP-2 and MMP-9 and
      caused lamellar explants to separate. MMP activation was deemed to have occurred
      if a specific MMP inhibitor, batimastat, blocked MMP activity and prevented
      lamellar separation. Thermolysin and streptococcal pyrogenic exotoxin B (SpeB)
      both separated explants dose-dependently but only thermolysin was inhibitable by
      batimastat or induced MMP activation equivalent to that seen with bacterial
      broths. Additionally, thermolysin and broth MMP activation appeared to be cell
      dependent as MMP activation did not occur in isolation. These results suggest the
      rapid increase in streptococcal species in the caecum and colon observed in
      parallel with carbohydrate induced equine laminitis may directly cause laminitis
      via production of exotoxin(s) capable of activating resident MMPs within the
      lamellar structure. Once activated, these MMPs can degrade key components of the
      basement membrane (BM) hemidesmosome complex, ultimately separating the BM from
      the epidermal basal cells resulting in the characteristic laminitis
      histopathology of hoof lamellae. While many different causative agents have been
      evaluated in the past, the results of this study provide a unifying aetiological
      mechanism for the development of carbohydrate induced equine laminitis.

PMID- 11240101
TI  - Serum antibody responses of cats to soluble whole cell antigens and isolated
      fimbriae of feline Porphyromonas salivosa (macacae) and associations with
      periodontal disease.
AB  - The whole cell soluble antigens of two strains (NCTC 11632 and VPB 3313) of
      feline Porphyromonas salivosa (macacae) were analyzed by Western blotting using
      serum taken from 40 domestic cats with various grades of periodontal disease.
      Nine strongly immunogenic protein bands (66, 52, 42, 29, 27, 23, 22, 21 and
      19kDa) were selected from both strains for further study. Both strains showed a
      significant association between overall periodontal grade and serum responses to
      the 66 and 21kDa bands with significant responses across both strains to all
      other bands except the 52kDa band. Similarly, both strains showed a significant
      association between the total colony forming units and serum responses to the 66
      and 42kDa bands with significant responses across both strains to all other bands
      except the 19kDa band. When sera from 25 of these cats were tested by Western
      blotting against the isolated fimbriae of VPB 3313, there was a significant
      association between the grade of response of cats to the 42kDa fimbrial
      preparation and (1) the total reactivity of the mouth (the sum of the responses
      to all individual whole cell antigens), (2) the total colony forming units of P.
      salivosa (macacae) at the premolar site, and (3) to their responsiveness to the
      42kDa band in the soluble whole cell antigen preparations. These findings suggest
      that P. salivosa (macacae) is a strong immunogen in the mouths of cats and those
      cats with more severe periodontal disease have a greater serum antibody
      reactivity to various soluble whole cell antigens, specifically including the
      fimbriae of this organism, than those with less severe periodontal disease.
      Overall, the findings suggest that this organism may be a contributor to
      periodontal disease in cats.

PMID- 11240102
TI  - Occurrence of Escherichia coli O157 in Finnish cattle.
AB  - Bovine faecal samples were collected during June-December 1997 at 14 major
      abattoirs slaughtering cattle in Finland. Escherichia coli O157 was isolated from
      19 of the 1448 samples (1.31%) after enrichment and immunomagnetic separation
      (IMS). The positive faecal isolates originated from 16 farms and eight abattoirs.
      The occurrence of E. coli O157 was highest in July (8/204; 3.92%) and September
      (6/244; 2.46%). No E. coli O157 was detected in November and December, nor from
      the faecal samples from the northernmost region where cattle density is low. All
      of the isolates carried the eae gene and showed the enterohaemolytic phenotype.
      All except one were motile and had the flagella antigen H7. Seventeen of the
      isolates were positive for stx(2) gene and one carried both the stx(1) and stx(2)
      genes. Of the 17 isolates with stx genes, 16 were verocytotoxin-positive in a
      reversed passive latex agglutination test after polymyxin extraction but only
      eight without extraction. The isolates belonged to 10 different pulsed-field gel
      electrophoresis (PFGE) patterns. The most common PFGE pattern (1.42) was detected
      in eight isolates (42.1%). Four PFGE patterns (1.1; 1.6; 1.12; 1.14) were
      identical with those isolated from humans in Finland, suggesting that at least
      some human E. coli O157 infections may be of bovine origin.

PMID- 11240103
TI  - Helicobacter spp. infection in cats: evaluation of the humoral immune response
      and prevalence of gastric Helicobacter spp.
AB  - The principal aims of this study were to evaluate the humoral immune response
      (IgG) of cats with gastric Helicobacter spp. infection, and to determine the
      prevalence of different types of Helicobacter spp. in the stomachs of cats. The
      Helicobacter infection status of 45 cats (12 healthy spay/neuter cats, 9 sick
      cats, 24 colony cats) was determined by evaluating endoscopic gastric biopsies
      for urease activity, presence of Helicobacter-like organisms (HLO) on
      histopathology, and genus and species-specific PCR. Serum samples were evaluated
      with a kinetic enzyme linked immunosorbent assay (ELISA) utilizing the high
      molecular cell-associated protein (HM-CAP) fraction of H. felis ATCC
      49179.Seventeen of 45 cats were infected with Helicobacter spp.: "H. heilmannii"
      9/17, H. felis 4/17, mixed "H. heilmannii" and H. felis 3/17, unclassified
      Helicobacter spp. 7/17. H. pylori was not detected in any cat. Kinetic ELISA
      results were significantly higher for infected cats, than for uninfected cats.
      Cats infected with different Helicobacter spp. showed similar distribution of
      OD/min values. There were no effects of age or clinical signs on the results of
      kinetic ELISA. No correlation between colonization density and seroconversion was
      observed. There were statistically significant, but weak correlations between the
      degree of seroconversion and the degree of inflammation, and the number of
      lymphoid follicles. Infected cats had more severe inflammation in the pylorus and
      fundus than uninfected cats. Infected sick cats had a higher degree of pyloric,
      but not fundic inflammation, than healthy infected cats and uninfected sick cats.
      The results indicate that naturally acquired infection with gastric Helicobacter
      spp. is associated with seroconversion (IgG) in cats. The similar ELISA values in
      cats infected with a variety of Helicobacter spp. suggests substantial antigenic
      homology between different Helicobacter spp. The higher degree of inflammation in
      infected than uninfected cats, supports a role for Helicobacter as a cause of
      gastritis in cats.

PMID- 11240104
TI  - Variation of the agr locus in Staphylococcus aureus isolates from cows with
      mastitis.
AB  - Staphylococcus aureus isolates from mastitic cow's milk were examined for
      production of alpha-hemolysin and protein A and their accessory gene regulator
      (agr locus) was analyzed. An inverse relationship between alpha-hemolysin and
      protein A production was found in most of the 76 isolates, suggesting that the
      isolates tested may be classified into group I (high alpha-hemolysin/low protein
      A), II (low alpha-hemolysin/high protein A), or III (low alpha-hemolysin/low
      protein A). The agr locus, which consists of hld, agrB, agrD, agrC, and agrA, was
      detected in most of the 78 isolates including two reference strains (Wood 46 and
      Cowan I) by polymerase chain reaction (PCR). When the PCR products for agr locus
      of 22 isolates from groups I and II were digested with restriction enzyme MboI,
      seven bands of the expected lengths were recognized in strain Wood 46, but not in
      the other isolates tested. Nucleotide sequence analysis of PCR products from six
      isolates revealed that the agr locus sequence of strain Wood 46 corresponded to
      that of the published sequence data, but the other five isolates from groups I
      and II diverged at agrB and agrD sequences and thus the deduced amino acid
      sequences. These variations of agr locus in S. aureus bovine isolates differed
      from those reported by Ji et al. [Science 276 (1997) 2027].

PMID- 11240105
TI  - Identification and sub-typing of Mycobacterium avium subsp. paratuberculosis and
      Mycobacterium avium subsp. avium by randomly amplified polymorphic DNA.
AB  - A commercially available kit consisting of twenty 10-mer random primers was
      evaluated to allow selection of a suitable primer that would permit
      identification and sub-typing of Mycobacterium avium subsp. paratuberculosis and
      Mycobacterium avium subsp. avium by randomly amplified polymorphic DNA (RAPD). A
      primer OPE-20 (5'-AAC-GGT-GAC-C-3') was identified to be the most suitable primer
      when tested with four ATCC reference strains of M. paratuberculosis and eight
      well characterized field strains each of M. paratuberculosis and M. avium. Primer
      OPE-20 was further tested for its ability to identify and subtype 200 field
      isolates of M. paratuberculosis. The fingerprint patterns of M. paratuberculosis
      (n=212) consisted of five unique common fragments (620, 450, 310, 230, 180bp) and
      nine variable fragments resulting in six distinct genotypes. The DNA fingerprints
      of M. avium (n=8) consisted of a single common fragment of 620bp, and 15 variable
      fragments resulting in six different genotypes. The cattle, human and goat
      isolates of M. paratuberculosis were genetically similar, but a sheep isolate had
      a different RAPD profile as compared to RAPD profiles from other species. RAPD
      was observed to be a rapid, reproducible and reliable technique for
      identification and sub-typing of M. paratuberculosis.

PMID- 11240106
TI  - An fMRI study of the functional neuroanatomy of picture encoding in younger and
      older adults.
AB  - Age-related changes in the neural mechanisms of picture encoding were
      investigated using functional magnetic resonance imaging (fMRI). Seven younger
      and seven older adults were studied while they were encoding pairs of concrete
      related, concrete-unrelated, and abstract pictures. Functional (T2*-weighted) and
      anatomical (T1-weighted) images of the brain were obtained using a 1.5 T MRI
      scanner. The results in the younger adults showed that the left dorsal prefrontal
      cortex (PFC) was activated during associative learning of the concrete-unrelated
      or abstract pictures. The results also suggest that both ventral and dorsal
      visual pathways are involved in the encoding of abstract pictures, and that the
      right superior parietal lobule likely mediates spatial information of the
      abstract pictures. The older adults showed significant activation in the left
      dorsal PFC under concrete-unrelated and abstract conditions. However, the older
      adults failed to activate either the left ventral and right dorsal PFC under the
      concrete-unrelated condition, or the parietal areas under abstract condition. A
      direct comparison between the two age groups demonstrates that the older adults
      had a reduced activation in the bilateral parieto-temporo-occipital areas under
      abstract condition, and in the right temporo-occipital area extending to the
      fusiform gyrus under the concrete-unrelated condition. Finally, age difference
      was found in correlation between memory performance and amplitude of signal
      change in the parahippocampal gyrus and fusiform gyrus under the concrete
      unrelated and abstract conditions. These changes in neural response likely
      underlie the age-related memory decline in relation to pictorial information.

PMID- 11240107
TI  - Neuroanatomical discrimination between manipulating and maintaining processes
      involved in verbal working memory; a functional MRI study.
AB  - We used functional magnetic resonance imaging (fMRI) to investigate neural
      correlates of processes concerning store and manipulation in verbal working
      memory. We prepared a revised lag 1 digit span, digit span and a simple number
      detection task. Specific activities in association with manipulating process were
      identified in the right middle (BA 9/46) and left precentral gyrus (BA 6).
      Activated areas specific to maintaining process were detected in the right middle
      (right BA 11/10) and medial (BA 6) frontal gyri, the right inferior parietal
      lobule (BA 40), and the left middle (BA 9) and inferior frontal gyri (BA 44). The
      process-nonspecific activated areas common to two processes were identified in
      the right inferior frontal gyrus (BA 47) and the left superior parietal lobule
      (BA 7). Using the signal percent change of each subject, we calculated the
      correlation coefficients among each activated area. The results of this analysis
      showed that two processes of verbal working memory were clearly discriminated.
      The two essential processes of manipulation and maintenance in working memory
      seem to activate process-specific and overlapping (process-nonspecific) areas,
      but the patterns of combination were definitely different.

PMID- 11240108
TI  - Recognition memory in normal aging and Parkinson's disease: behavioral and
      electrophysiologic measures.
AB  - To assess effects of normal aging and Parkinson's disease (PD) on recognition
      memory, we examined the N400 component of event-related potentials (ERPs) and
      behavioral measures during a recognition memory task in 17 normal young subjects,
      17 normal elderly subjects, and 17 patients with PD. To elicit ERPs, some words
      were repeated immediately after initial presentation (at lag 0), while others
      were repeated after one intervening word (at lag 1) or at lag 6. Subjects were
      requested to push a button with the right thumb upon first presentation of a word
      and with the left thumb upon repeat presentation. Compared to the normal young
      subjects, normal elderly subjects showed reduced accuracy in recognizing repeated
      words at lags 1 and 6. Compared to the normal elderly group, PD patients showed
      decreased accuracy in recognizing lag 6 repetition. N400 amplitude did not differ
      between the two normal groups, while PD patients showed lower N400 amplitudes
      than normal elderly subjects. The N400 in the young group showed attenuation for
      lags 0, 1 and 6 repetitions, while attenuations in the elderly group and the PD
      group were noted only for lags 0 and 1 repetitions. These data suggest intact
      immediate but impaired delayed recognition memory in aging and in PD. In
      addition, recognition memory deficits in PD may result, at least partly from the
      impairment of context integration process.

PMID- 11240109
TI  - Theta power in the EEG of humans during ongoing processing in a haptic object
      recognition task.
AB  - Dynamic changes in spectral theta power (TP) in the EEG over frontal regions were
      reported previously during the processing of visually presented spatial and
      verbal tasks [Cereb. Cortex, 7 (1997) 374-385]. Lower TP was found at the
      beginning compared to the end of processing. In order to test another modality,
      we examined theta power during the exploration of haptic stimuli with different
      complexity. A linear correlation between theta power and mean exploration time
      (as a measure of stimulus complexity) was found at the end of exploration but not
      at its beginning. These data are in line with our hypothesis since one could
      expect minimal load of working memory independent of stimulus complexity at the
      beginning of exploration whereas working memory would have integrated the stimuli
      of differing complexity into a perceptual model at the end of exploration.

PMID- 11240110
TI  - Heterotopic painful stimulation decreases the late component of somatosensory
      evoked potentials induced by electrical tooth stimulation.
AB  - The purpose of this study was to determine the relationship between the late
      component of somatosensory evoked potentials (SEP) induced by electrical tooth
      stimulation and subjective pain estimation when heterotopically painful
      stimulation was delivered to humans. The noxious electrical conditioning stimuli
      were applied to the left median nerve in noxious session I and the right median
      nerve in noxious session II for 10 min. The amplitude of the late component and
      visual analogue scale (VAS) value were both decreased significantly by
      conditioning stimuli in both sessions. The maximum decreases in SEP amplitude and
      VAS value induced by conditioning stimuli were respectively 40.2 and 37.2% in
      noxious session I and 49.3 and 42.3% in noxious session II. After-effect was
      observed 5 min after removal of the conditioning stimuli. The rates of decrease
      were thus nearly the same and independent of the site of conditioning stimulation
      in noxious sessions I and II. The SEP amplitude was significantly correlated with
      VAS values. The present study revealed that SEP amplitude and subjective pain
      intensity estimated by VAS following electrical tooth stimulation can be
      decreased by noxious stimuli to hand. This finding that heterotopic painful
      stimulation attenuates experimentally-induced tooth pain suggests a triggering of
      diffuse noxious inhibitory control (DNIC) with after-effect in trigeminal region.

PMID- 11240111
TI  - Event-related brain responses to morphological violations in Catalan.
AB  - The ERP (event-related potential) violation paradigm was used to investigate
      brain responses to morphologically correct and incorrect verb forms of Catalan.
      Violations of stem formation and inflectional processes were examined in separate
      experimental conditions. Our most interesting finding is that misapplications of
      stem formation rules elicit an early left preponderant negativity. This
      complements our previous ERP results on morphological violations in other
      languages in which misapplications of inflectional rules were shown to produce
      such effects. We make use of the linguistic distinction between lexically stored
      and rule-based word forms and suggest a unified interpretation of the
      experimental results, arguing that these negativities vary as a function of
      processes involved in morpho-syntactic structure building.

PMID- 11240112
TI  - ERP time course of perceptual and post-perceptual mechanisms of spatial
      selection.
AB  - Event-related potentials (ERPs) were recorded from volunteers performing a task
      requiring simple judgements about the spatial location of a single target that
      could appear with equal probability to the left or right of fixation. A robust
      finding in the ERP literature is a dichotomy between attentional selection for
      spatial and non-spatial features. Visual spatial selection is manifest as a
      modulation of early components (P1, N1) that reveal exogenous processes, while
      non-spatial selection is revealed by the presence of longer latency endogenous
      components (N2). We present an analysis of several conditions that require
      different degrees of visual analysis to confirm the location of the single
      target, and show that spatial selection can be manifest at early (N1) or later
      (N2) stages. Observers identified the location of targets that were more salient
      (2D line drawings with abrupt onset) or less salient (2D line drawings without
      abrupt onset or 3D objects embedded in random-dot stereograms). We examined
      differences in amplitude, latency, and topography of early ERP components (P1,
      N1, P2, N2), and compared responses measured over the left and right hemispheres
      in response to left and right targets. The results support the hypothesis that
      the processes involved in spatial selection can be manifest at early or late
      stages, dependent on the quality of the incoming data. Moreover, the iterative
      process by which the percept is established benefits from a change in the visual
      input that is specific to the target.

PMID- 11240113
TI  - Attention and successful episodic encoding: an event-related potential study.
AB  - Event-related potentials (ERPs) were used to delineate the cerebral processes
      occurring when information is encoded into episodic memory and to determine how
      these processes are affected by divided attention. ERPs were recorded during
      encoding under focused or divided attention, and were selectively averaged on the
      basis of their retrieval during later free recall and recognition tests (with
      remember-know judgments). Items retrieved with conscious recollection of the
      encoding episode (remembered, recalled) were distinguished at encoding from later
      missed items by an enhanced left fronto-temporal negative wave (N340), a negative
      posterior sustained potential and a positive frontal sustained potential. These
      effects occurred independently of the level of attention. Items later retrieved
      on the basis of familiarity (known) elicited a larger N340 than missed items, but
      did not demonstrate the increased sustained potentials. We suggest that item
      specific conceptual processing (N340) is sufficient to produce familiarity-based
      recognition, but additional elaborative processing (sustained interaction of
      frontal and posterior regions) is necessary for conscious recollection. The
      effect of divided attention on these processes was related to the difficulty of
      the secondary task, with the more difficult task causing greater and earlier
      interference.

PMID- 11240114
TI  - Functional organization of the lateral premotor cortex: fMRI reveals different
      regions activated by anticipation of object properties, location and speed.
AB  - Previous studies have provided evidence that the lateral premotor cortex (PMC) is
      involved in representations triggered by attended sensory events. However, while
      the functional specificity of subregions of this large cortical structure has
      been intensively investigated in the monkey, little is known about functional
      differences within human lateral premotor areas. In the present study, functional
      magnetic resonance imaging was used to investigate if attending to object
      specific (O), spatial (S), or temporal (T) properties of the same sensory event,
      i.e. moving objects, involves different premotor areas. We found a frontoparietal
      'prehension network' comprising the pre-supplementary motor area (preSMA), the
      ventral PMC, and the left anterior intraparietal sulcus (aIPS) to be activated
      independently of the attended stimulus property, but most intensively during
      object-related attention. Moreover, several areas were exclusively activated
      according to the attended stimulus property. Particularly, different PMC regions
      responded to the Object (O) task (left superior ventrolateral PMC), the Spatial
      (S) task (dorsolateral PMC), and the Timing (T) task (frontal opercular cortex
      (FOP)). These results indicate that the representation of different stimulus
      dimensions engage distinct premotor areas and, therefore, that there is a
      functional specificity of lateral premotor subregions.

PMID- 11240115
TI  - Dissociating memory processes involved in direct and indirect tests with ERPs to
      unfamiliar faces.
AB  - Event-related potentials (ERPs) were recorded during indirect and direct memory
      tests for unfamiliar faces. In both tests, ERPs displayed the usual positive
      shift known as the ERP repetition effect. In the indirect test, this effect
      includes parietal effect (the usual N400 effect) and a right fronto-central
      effect. Both effects are also present in the direct test. Two additional effects
      are present only in the direct test. These effects are an early fronto-polar
      effect and a late posterior effect (the usual P600 effect). These findings are
      taken as support for the distinction between 'associative' processes elicited in
      both the direct and indirect tests, and 'episodic' processes elicited only in the
      direct test. This task dissociation could well provide a scalp correlate of the
      distinction between the neocortical and cortico-limbic systems that have been
      shown to contribute respectively to associative and episodic processing. In
      addition, it is proposed that the dissociation between the two frontal effects
      could be accounted for by a distinction between the processing of intrinsic vs.
      extrinsic contextual attributes as a function of the task requirements.

PMID- 11240117
TI  - Frontal evaluation and posterior representation in target detection.
AB  - This study examined the topography of the event-related potential in visual
      spatial compared to visual-object target detection. The initial index of target
      detection in the ERP was an inferior anterior P2a accompanied by a posterior N2b.
      Single unit studies in the monkey indicate that the detection of task-relevant
      stimuli requires interaction between prefrontal cortex and perceptual
      representation areas in the posterior brain. The posterior brain processes the
      physical features of stimuli while frontal cortex performs higher-order
      operations, such as evaluating the task-relevance of a stimulus. Target detection
      requires an interaction between feature representations and relevance
      representations. We hypothesize that the P2a and N2b ERP indices of target
      detection reflect this frontal/posterior interaction. Visual-spatial feature
      information is processed in the dorsal posterior brain (posterior parietal
      cortex) and visual-object information is processed in the ventral posterior brain
      (inferior occipito-temporal cortex). We observed that at the peak of the P2a the
      N2b was located over posterior dorsal leads in visual-spatial target detection
      and over posterior ventral leads in visual-object target detection. The P2a was
      largest over inferior prefrontal leads in both tasks. We suggest that this
      distribution is consistent with interaction between orbitofrontal cortical areas
      of salience representation and posterior cortical areas of stimulus feature
      representation.

PMID- 11240116
TI  - Event-related brain response abnormalities in autism: evidence for impaired
      cerebello-frontal spatial attention networks.
AB  - Although under some conditions the attention-related late positive event-related
      potential (ERP) response (LPC) is apparently normal in autism during visual
      processing, the LPC elicited by visuospatial processing may be compromised.
      Results from this study provide evidence for abnormalities in autism in two
      components of the LPC generated during spatial processing. The early frontal
      distribution of the LPC which may reflect attention orienting was delayed or
      missing in autistic subjects during conditions in which attention was to
      peripheral visual fields. The later parietal distribution of the LPC which may be
      associated with context updating was smaller in amplitude in autistic subjects
      regardless of attention location. Both abnormalities suggest disruption of
      function in spatial attention networks in autism. Evidence that the cerebellar
      abnormalities in autism may underlie these deficits comes from: (1) similar
      results in ERP responses and spatial attention deficits in patients with
      cerebellar lesions; (2) brain-behavior correlations in normally functioning
      individuals associating the size of the posterior cerebellar vermis and the
      latency of the frontal LPC; and (3) a previously reported complementary
      correlation between the size of the posterior vermal lobules and spatial
      orienting speed. Although the scalp-recorded LPC is thought to be cortically
      generated, it may be modulated by subcortical neural activity. The cerebellum may
      serve as a modulating influence by affecting the task-related antecedent
      attentional process. The electrophysiological abnormalities reported here index
      spatial attention deficits in autism that may reflect cerebellar influence on
      both frontal and parietal spatial attention function.

PMID- 11240118
TI  - Shifting attention between objects.
AB  - Experiment 1 used a modified spatial cueing paradigm that was introduced by Egly
      et al. [J. Exp. Psychol. Gen. 123 (1994) 161] to investigate the cost incurred in
      shifting attention within an object as opposed to shifting attention between
      objects. Subjects were presented with two outline rectangles and had to detect a
      target (a luminance increment) that could appear in the cued location (valid
      trials), in an uncued location inside the cued rectangle (inside-invalid trials),
      or in an uncued location inside the uncued rectangle (outside-invalid trials).
      Valid trials were faster than invalid trials, and inside-invalid trials were
      faster than outside-invalid trials. In Experiment 2, the two rectangles were
      joined to form a unitary object. Here, no difference was found between outside
      invalid trials and inside-invalid trials. Experiment 3 showed that the delayed
      response on outside-invalid trials in Experiment 1 was not due to attention
      needing to cross the figural borders in order to re-orient to the uncued
      rectangle. The results were interpreted as showing that an extra cost is incurred
      for shifting attention between different objects.

PMID- 11240119
TI  - Visually based path-planning by Japanese monkeys.
AB  - To construct an animal model of strategy formation, we designed a maze path
      finding task. First, we asked monkeys to capture a goal in the maze by moving a
      cursor on the screen. Cursor movement was linked to movements of each wrist. When
      the animals learned the association between cursor movement and wrist movement,
      we established a start and a goal in the maze, and asked them to find a path
      between them. We found that the animals took the shortest pathway, rather than
      approaching the goal randomly. We further found that the animals adopted a
      strategy of selecting a fixed intermediate point in the visually presented maze
      to select one of the shortest pathways, suggesting a visually based path
      planning. To examine their capacity to use that strategy flexibly, we transformed
      the task by blocking pathways in the maze, providing a problem to solve. The
      animals then developed a strategy of solving the problem by planning a novel
      shortest path from the start to the goal and rerouting the path to bypass the
      obstacle.

PMID- 11240120
TI  - Visual contrast sensitivity in deaf versus hearing populations: exploring the
      perceptual consequences of auditory deprivation and experience with a visual
      language.
AB  - Early deafness in humans provides a unique opportunity to examine the perceptual
      consequences of altered sensory experience. In particular, visual perception in
      the deaf may be altered as a result of their auditory deprivation and/or because
      the deaf rely heavily upon a visual language (American Sign Language, or ASL, in
      the US). Recently, we found that deaf, but not hearing, subjects exhibit a right
      visual field/left hemisphere advantage on a low-level direction of motion task, a
      finding that has been attributed to the deaf's experience with ASL [Psychol. Sci.
      10 (1999) 256; Brain Res. 405 (1987) 268]. In order to determine whether this
      visual field asymmetry generalizes to other low-level visual functions, in this
      study we measured contrast sensitivity in deaf and hearing subjects to moving
      stimuli over a range of speeds (0.125-64 degrees /s). We hypothesized that if ASL
      use drives differences between hearing and deaf subjects, such differences may
      occur over a restricted range of speeds most commonly found in ASL. In addition,
      we tested a third group, hearing native signers who learned ASL early from their
      deaf parents, to further assess whether potential differences between groups
      results from ASL use. These experiments reveal no overall differences in contrast
      sensitivity, nor differences in visual field asymmetries, across subject groups
      at any speed tested. Thus, differences previously observed between deaf and
      hearing subjects for discriminating the direction of moving stimuli do not
      generalize to contrast sensitivity for moving stimuli, a result that has
      implications for the neural level at which plastic changes occur in the visual
      system of deaf subjects.

PMID- 11240121
TI  - Expression and characterization of a magnetosome-associated protein, TPR
      containing MAM22, in Escherichia coli.
AB  - A magnetosome-associated protein, MAM22, contains a TPR domain (five TPR motifs
      and one putative TPR motif) that has been known to mediate protein-protein
      interactions. We expressed the mam22 gene in Escherichia coli and found that the
      purified MAM22 was reversibly self-aggregated by NaCl. The structural model of
      MAM22 which has been proposed on the basis of the crystal structure of the N
      terminal TPR domain of a human Ser/Thr protein phosphatase suggests the novel
      hydrophobic colloidal features of MAM22 with TPR motifs.

PMID- 11240122
TI  - Crystal structure of the oxidized cytochrome c(2) from Blastochloris viridis.
AB  - The crystal structure of the oxidized cytochrome c(2) from Blastochloris
      (formerly Rhodopseudomonas) viridis was determined at 1.9 A resolution.
      Structural comparison with the reduced form revealed significant structural
      changes according to the oxidation state of the heme iron. Slight perturbation of
      the polypeptide chain backbone was observed, and the secondary structure and the
      hydrogen patterns between main-chain atoms were retained. The oxidation state
      dependent conformational shifts were localized in the vicinity of the methionine
      ligand side and the propionate group of the heme. The conserved segment of the
      polypeptide chain in cytochrome c and cytochrome c(2) exhibited some degree of
      mobility, interacting with the heme iron atom by the hydrogen bond network. These
      results indicate that the movement of the internal water molecule conserved in
      various c-type cytochromes drives the adjustments of side-chain atoms of nearby
      residue, and the segmental temperature factor changes along the polypeptide
      chain.

PMID- 11240123
TI  - Stimulation of p38 MAP kinase reduces acidosis and Na(+) overload in
      preconditioned hepatocytes.
AB  - Ischemic preconditioning has been shown to improve liver resistance to
      hypoxia/reperfusion damage. A signal pathway involving A(2A)-adenosine receptor,
      G(i)-proteins, protein kinase C and p38 MAP kinase is responsible for the
      development of hypoxic preconditioning in hepatocytes. However, the coupling of
      this signal pathway with the mechanisms responsible for cytoprotection is still
      unknown. We have observed that stimulation of A(2A)-adenosine receptors or of p38
      MAPK by CGS21680 or anisomycin, respectively, appreciably reduced intracellular
      acidosis and Na(+) accumulation developing during hypoxia. These effects were
      reverted by p38 MAPK inhibitor SB203580 as well as by blocking vacuolar proton
      ATPase with bafilomycin A(1). SB203580 and bafilomycin A(1) also abolished the
      cytoprotective action exerted by both CGS21680 and anisomycin. We propose that
      the stimulation of p38 MAPK by preconditioning might increase hepatocyte
      resistance to hypoxia by activating proton extrusion through vacuolar proton
      ATPase, thus limiting Na(+) overload promoted by Na(+)-dependent acid buffering
      systems.

PMID- 11240124
TI  - Tetraplex formation by the progressive myoclonus epilepsy type-1 repeat:
      implications for instability in the repeat expansion diseases.
AB  - The repeat expansion diseases are a group of genetic disorders resulting from an
      increase in size or expansion of a specific array of tandem repeats. It has been
      suggested that DNA secondary structures are responsible for this expansion. If
      this is so, we would expect that all unstable repeats should form such
      structures. We show here that the unstable repeat that causes progressive
      myoclonus epilepsy type-1 (EPM1), like the repeats associated with other diseases
      in this category, forms a variety of secondary structures. However, EPM1 is
      unique in that tetraplexes are the only structures likely to form in long
      unpaired repeat tracts under physiological conditions.

PMID- 11240125
TI  - A novel patatin-like gene stimulated by drought stress encodes a galactolipid
      acyl hydrolase.
AB  - A cDNA (Vupat1) encoding a predicted 43 kDa protein was isolated from drought
      stressed cowpea (Vigna unguiculata) leaves. It has homology with patatin, a
      potato tuber storage protein with lipolytic acyl hydrolase activity. The
      recombinant protein VUPAT1 expressed in the baculovirus system displays
      preferentially galactolipid acyl hydrolase activity. Phospholipids are very
      slowly hydrolyzed and apparently triacylglycerols are not deacylated. Vupat1
      promoter contains putative drought-inducible sequences. Northern blots showed
      that gene expression is stimulated by drought stress and is more pronounced in a
      drought-sensitive cultivar than in a drought-tolerant one. An involvement in
      drought-induced galactolipid degradation is proposed for VUPAT1.

PMID- 11240126
TI  - Identification and kinetic analysis of the interaction between Nck-2 and DOCK180.
AB  - Nck-2 is a newly identified adapter protein comprising three N-terminal SH3
      domains and one C-terminal SH2 domain. We have identified in a yeast two-hybrid
      screen DOCK180, a signaling protein implicated in the regulation of membrane
      ruffling and migration, as a binding protein for Nck-2. Surface plasmon resonance
      analyses reveal that the second and the third SH3 domains interact with the C
      terminal region of DOCK180. The interactions mediated by the individual SH3
      domains, however, are much weaker than that of the full length Nck-2.
      Furthermore, a point mutation that inactivates the second or the third SH3 domain
      dramatically reduced the interaction of Nck-2 with DOCK180, suggesting that both
      SH3 domains contribute to the DOCK180 binding. A major Nck-2 binding site, which
      is recognized primarily by the third SH3 domain, has been mapped to residues 1819
      1836 of DOCK180. Two additional, albeit much weaker, Nck-2 SH3 binding sites are
      located to DOCK180 residues 1793-1810 and 1835-1852 respectively. Consistent with
      the mutational studies, kinetic analyses by surface plasmon resonance suggest
      that two binding events with equilibrium dissociation constants of 4.15+/-1.9x10(
      7) M and 3.24+/-1.9x10(-9) M mediate the binding of GST-Nck-2 to GST fusion
      protein containing the C-terminal region of DOCK180. These studies identify a
      novel interaction between Nck-2 and DOCK180. Furthermore, they provide a detailed
      analysis of a protein complex formation mediated by multiple SH3 domains
      revealing that tandem SH3 domains significantly enhance the weak interactions
      mediated by each individual SH3 domain.

PMID- 11240127
TI  - Inhibition of gap junctional intercellular communication in rat liver epithelial
      cells with transforming RNA.
AB  - Previous studies indicated that transforming RNA, derived from the 3' half of the
      U5 small nuclear RNA first stem structure, suppressed the secretory protein
      translation in vitro. Gap junctions facilitate homeostatic control of cell growth
      and differentiation and their dysfunction has been correlated with
      carcinogenesis. Here, we reported that transforming RNA directly suppressed the
      gap junction protein, connexin 43, translation and thereby inhibited functional
      gap junction function in rat epithelial cells. Together with previous data, this
      implies that altered expression of transforming RNA itself is a potential
      mechanism in inhibiting gap junction function during carcinogenesis.

PMID- 11240128
TI  - Interactions of the XylS regulators with the C-terminal domain of the RNA
      polymerase alpha subunit influence the expression level from the cognate Pm
      promoter.
AB  - The Pseudomonas putida meta-cleavage operon encodes the enzymes for the
      catabolism of alkylbenzoates. Activation of meta-operon transcription is mediated
      by the XylS protein which, upon activation by effectors, binds two sites between 
      70 and -35 with respect to the main transcription initiation point at the Pm
      promoter. Two naturally occurring regulators, XylS and XylS1, that differ by only
      five amino acids, have been analyzed with regard to potential interactions of
      these positive regulators with the C-terminal domain of the alpha subunit of RNA
      polymerase (alpha-CTD). For these studies we expressed a derivative of alpha
      deprived of the entire C-terminal domain (alpha-Delta235) and found that
      expression from Pm with XylS or XylS1 was significantly decreased. To discern
      whether alpha-CTD activation depended on interactions with DNA and/or XylS
      proteins we tested a large collection of alanine substitutions within alpha-CTD.
      Most substitutions that had an effect on XylS and XylS1-dependent transcription
      were located in or adjacent to helix 1 and 4, which are known to be involved in
      alpha-CTD interactions with DNA. Two alanine substitutions in helix 3 (residues
      287 and 291) identified a putative region of alpha-CTD/XylS regulator
      interactions.

PMID- 11240129
TI  - Differential skeletal muscle expression of myostatin across teleost species, and
      the isolation of multiple myostatin isoforms.
AB  - Two myostatin (MSTN) isoforms were isolated from brook trout with 92% identity in
      corresponding regions at the nucleotide level. One isoform was isolated from
      muscle and brain and the second from ovarian tissue. To our knowledge this is the
      first time two MSTN isoforms have been isolated from a given vertebrate species.
      Within the brain, MSTN transcripts were localized to the optic lobes, hindbrain,
      and hypothalamus. In the trout ovary, MSTN transcripts were upregulated at
      ovulation in several females. MSTN cDNA fragments were also isolated from several
      other fish species and differential expression of MSTN among muscle fiber types
      was observed.

PMID- 11240130
TI  - New polypeptide components purified from mamba venom.
AB  - New polypeptide components have been isolated from Dendroaspis angusticeps venom
      using chromatography. Two polypeptides containing 59 and 57 amino acids, called
      'DaE1' and 'DaE2' respectively, have been purified to homogeneity and fully
      sequenced. Spectrometric analysis yielded masses of 6631.5 and 6389.0 Da,
      respectively. The polypeptides share 98 and 95% identity, respectively, with
      trypsin inhibitor E (DpE) of Dendroaspis polylepis polylepis. 'DaE' polypeptides
      inhibit Kv1.1 channels with an IC(50) value in the range of 300 nM. They can be
      considered as new dendrotoxins, albeit with fairly low affinity as compared to
      alpha-DTX. 'DaE' polypeptides do not affect Kir2.1 channels.

PMID- 11240131
TI  - Membrane type 1 matrix metalloproteinase and gelatinase A synergistically degrade
      type 1 collagen in a cell model.
AB  - A fibrosarcoma cell line transfected with the matrix metalloproteinase MT1 MMP
      showed an enhanced ability to degrade 14C-labelled collagen films. As previously
      shown for proMMP 2 activation, TIMP 1 was an ineffective inhibitor of the process
      of collagenolysis whereas TIMP 2 was efficient and completely prevented collagen
      degradation. In the presence of the calcium ionophore, ionomycin, proteolytic
      processing of MT1 MMP was restricted and collagenolysis did not occur indicating
      that the 63 kDa form of the enzyme is not a functional collagenase. The
      collagenolytic activity of MT1 MMP was shown to be enhanced by the addition of
      proMMP 2, but TIMP 1 inhibition remained poor relative to that of TIMP 2. The
      study demonstrated that synergy between two non-conventional collagenases
      effectively degrades insoluble pericellular collagen. Due to the membrane
      localisation of MT1 MMP, this could potentially occur in a highly localised
      manner.

PMID- 11240132
TI  - Photoactivation and calcium sensitivity of the fluorescent NO indicator 4,5
      diaminofluorescein (DAF-2): implications for cellular NO imaging.
AB  - The fluorescent indicator of nitric oxide (NO), 4,5-diaminofluorescein (DAF-2),
      and its membrane-permeable derivative (DAF-2 diacetate) have been recently
      developed to perform real-time biological imaging of NO. In this study, we show
      that DAF-2 is strongly influenced by factors other than the concentration of NO
      itself. Using measurements with a fluorimeter as well as fluorescence microscopy,
      we found that the divalent cation concentration in the medium, as well as the
      incident light, strongly affects the ability of DAF-2 to detect NO. Calcium, in
      particular, enhanced the signal detection of NO released by NO donors by up to
      200 times. With multiple and longer exposures to light, no bleaching of the dye
      was observed but, instead, a potentiation of the fluorescence response could be
      measured. While these two properties will affect the use and interpretation of
      the hitherto acquired data with this fluorescent compound, they may also open up
      new possibilities for its application.

PMID- 11240133
TI  - Desialylation of extracellular GD1a-neoganglioprotein suggests cell surface
      orientation of the plasma membrane-bound ganglioside sialidase activity in human
      neuroblastoma cells.
AB  - The orientation of the catalytic site of a ganglioside-specific sialidase in the
      plasma membrane of SK-N-MC neuroblastoma cells was probed using water-soluble
      GD1a-neoganglioprotein substrate on intact cells and GM1-product detection by
      cholera toxin B. Desialylation of substrate was readily observed, whereas
      specific sialidase inhibitors prevented the reaction, and conditioned medium was
      inactive. Inhibitors of endocytosis and acidification had no effect on substrate
      degradation, and lowering temperature to 18 degrees C reduced activity but did
      not abolish it. We conclude that the ganglioside sialidase activity is cell
      surface-orientated and displays an in situ specificity that mirrors enzyme
      preparations in vitro.

PMID- 11240134
TI  - Homeobox gene clusters and the human paralogy map.
AB  - Homeobox genes encode important developmental control proteins. In vertebrates,
      those encoding the proteins of the HOX class and their most closely related
      families, including paraHOX and metaHOX classes, are clustered in paralogous
      regions (or paralogons). We show that the majority of the other homeobox genes
      (we called contraHOX) can also be clustered and belong to paralogons in humans.
      This suggests that they duplicated during vertebrate evolution along the same
      processes as the HOX genes. We tentatively assembled several paralogons in
      superparalogons. One of the superparalogons contains the contraHOX genes. These
      observations were extended to hundreds of genes, and allowed to describe a
      primary human genome paralogy map.

PMID- 11240135
TI  - Multiple Holliday junction resolving enzyme activities in the Crenarchaeota and
      Euryarchaeota.
AB  - Holliday junction resolving enzymes are required by all life forms that catalyse
      homologous recombination, including all cellular organisms and many bacterial and
      eukaryotic viruses. Here we report the identification of three distinct Holliday
      junction resolving enzyme activities present in two highly divergent archaeal
      species. Both Sulfolobus and Pyrococcus share the Hjc activity, and in addition
      possess unique secondary activities (Hje and Hjr). We propose by analogy with the
      two other domains of life that the latter enzymes are viral in origin, suggesting
      the widespread existence of archaeal viruses that rely on homologous
      recombination as part of their life cycle.

PMID- 11240136
TI  - Activity and mRNA abundance of Delta-5 and Delta-6 fatty acid desaturases in two
      human cell lines.
AB  - We analyzed fatty acid biosynthesis in Chang and ZR-75-1 cells. Both cell lines
      could desaturate and further elongate substrates for Delta-5 desaturase. ZR-75-1
      but not Chang cells showed Delta-6 desaturation of 18:2n-6, 18:3n-3, 24:4n-6 and
      24:5n-3. In both cell lines, the mRNA abundance can be related to Delta-5 or
      Delta-6 fatty acid desaturase activities. These results suggest that desaturase
      genes could have, at least in part, independent control mechanisms and that Delta
      6 desaturase impairment is not specific to any particular step of the fatty acid
      metabolic pathways, which may diminish the rationale for the existence of at
      least two distinct enzymes.

PMID- 11240137
TI  - In vitro glucuronidation of xanthohumol, a flavonoid in hop and beer, by rat and
      human liver microsomes.
AB  - Xanthohumol (XN) is the major prenylated flavonoid of hop plants and has been
      detected in beer. Previous studies suggest a variety of potential cancer
      chemopreventive effects for XN, but there is no information on its metabolism.
      The aim of this study was to investigate in vitro glucuronidation of XN by rat
      and human liver microsomes. Using high-performance liquid chromatography, two
      major glucuronides of XN were found with either rat or human liver microsomes.
      Release of the aglycone by enzymatic hydrolysis with beta-glucuronidase followed
      by liquid chromatography/mass spectrometry and nuclear magnetic resonance
      analysis revealed that these were C-4' and C-4 monoglucuronides of XN.

PMID- 11240138
TI  - Conserved amino acids near the carboxy terminus of bacterial tyrosyl-tRNA
      synthetase are involved in tRNA and Tyr-AMP binding.
AB  - Bacterial tyrosyl-tRNA synthetases occur in two large subfamilies, TyrRS and
      TyrRZ, that possess about 25% amino acid identity. Their amino-terminal region,
      the active site domain, is more conserved (>36% identity). The carboxy-terminal
      segment of these enzymes includes the tRNA binding domain and contains only few
      conserved residues. Replacement of three of these residues in Acidithiobacillus
      ferrooxidans TyrRZ revealed that S356 and K395 play roles in tRNA binding, while
      H306, a residue at the junction of the catalytic and tRNA binding domains,
      stabilizes the Tyr-AMP:TyrRZ complex. The replacement data suggest that conserved
      amino acids in A. ferrooxidans TyrRZ and Bacillus stearothermophilus TyrRS play
      equivalent roles in enzyme function.

PMID- 11240139
TI  - Study of the cytolethal distending toxin (CDT)-activated cell cycle checkpoint.
      Involvement of the CHK2 kinase.
AB  - The bacterial cytolethal distending toxin (CDT) triggers a G2/M cell cycle arrest
      in eukaryotic cells by inhibiting the CDC25C phosphatase-dependent CDK1
      dephosphorylation and activation. We report that upon CDT treatment CDC25C is
      fully sequestered in the cytoplasmic compartment, an effect that is reminiscent
      of DNA damage-dependent checkpoint activation. We show that the checkpoint kinase
      CHK2, an upstream regulator of CDC25C, is phosphorylated and activated after CDT
      treatment. In contrast to what is observed with other DNA damaging agents, we
      demonstrate that the activation of CHK2 can only take place during S-phase. Use
      of wortmannin and caffeine suggests that this effect is not dependent on ATM but
      rather on another as yet unidentified PI3 kinase family member. These results
      confirm that the CDT is therefore responsible for specific genomic injuries that
      block cell proliferation by activating a cell cycle checkpoint.

PMID- 11240140
TI  - Retinol binding protein expression is induced in HepG2 cells by zinc deficiency.
AB  - Zinc (Zn) deficiency is often associated with low plasma vitamin A (retinol)
      concentrations. It has been suggested that the reduction in plasma retinol is
      secondary to reduced liver retinol binding protein (RBP) synthesis. In the
      present study, RBP expression was determined in HepG2 cells cultured in either Zn
      adequate media or chelated media containing varying concentrations of Zn. Levels
      of RBP mRNA increased in a time- and Zn concentration-dependent manner such that
      0.5 microM Zn-treated cells exhibited a >7.5-fold increase while cells treated
      with 15 microM Zn were increased 2.9-fold at 72 h compared to controls. RBP
      protein also progressively increased by 72 h to levels >8-fold and 3-fold higher
      than controls, in 0.5 microM and 15 microM Zn-treated cells, respectively. The
      increase in RBP occurred without any change in DNA concentration between groups
      through 72 h. The Zn deficiency-induced elevations in RBP transcript levels could
      be reversed within 24-48 h of repletion in Zn adequate media. Thus, the
      reductions in plasma retinol observed in Zn deficiency are in part a direct
      consequence of the deficiency.

PMID- 11240141
TI  - Hematopoietic cell-specific adapter proteins, SLP-76 and BLNK, effectively
      activate NF-AT as well as NF-kappaB by Syk and Tec PTKs in non-lymphoid cell
      lines.
AB  - To investigate the roles of various hematopoietic cell-specific adapter proteins
      in T cell receptor (TCR)-signaling leading to nuclear factor of activated T cell
      (NF-AT) and nuclear factor of kappaB (NF-kappaB) activation, we reconstituted TCR
      signaling with CD8/zeta, various protein tyrosine kinases (PTKs), and adapter
      proteins in a non-lymphoid cell line, 293T. We show that SLP-76 and BLNK, but not
      LAT, effectively co-operated with Syk and Tec family PTKs to activate NF-AT and
      NF-kappaB. We also show that Tec family PTKs enhanced endogenous phospholipase C
      (PLC)-gamma1 phosphorylation induced by CD8/zeta and Syk in 293T cells. These
      results imply that PLC-gamma1 may play a critical role in a hematopoietic cell
      specific adapter protein-mediated NF-AT and NF-kappaB activation in a non
      lymphoid cell.

PMID- 11240142
TI  - Nuclear localization of protein phosphatase 5 is dependent on the carboxy
      terminal region.
AB  - Endogenous and overexpressed protein phosphatase 5 (PP5) localizes to the nucleus
      and cytoplasm of HeLa cells, while the overexpressed TPR domain of PP5 is
      restricted to the cytoplasm. Deletion and mutational analysis of human PP5
      demonstrates that the C-terminal amino acids 420-499 are essential for nuclear
      localization and PP5 activity is not required. Since the phosphatase domain
      terminates at 473, these studies suggest that the highly conserved section (476
      491) with the eukaryotic consensus FXAVPHPXPhiXPMAYAN is required for nuclear
      localization of PP5. Bacterially expressed PP5 is inhibited by several tumor
      promoters but not by the anticancer drug fostriecin.

PMID- 11240143
TI  - Hydrophobic analogues of the winter flounder 'antifreeze' protein.
AB  - The synthesis, solution conformation and ice-growth inhibition properties of four
      new analogues of the type I 37-residue winter flounder 'antifreeze' protein are
      reported. All four analogues contain two extra salt bridges to facilitate
      comparison of results with previously published data. In two analogues, all four
      threonine residues in the native polypeptide were mutated to 2-amino butyric acid
      (an unnatural amino acid) and isoleucine, respectively. The butyric acid analogue
      was approximately 85% helical at 3 degrees C, modified the shape of ice growth,
      and exhibited reduced hysteresis compared to the native protein (9% at 4 mM).
      These results show that the gamma-methyl group of threonine, which is present in
      the sidechain of 2-amino butyric acid, is not sufficient for activity. The
      isoleucine analogue, in which the threonine hydroxyl group is replaced by an
      ethyl group, was 100% helical at 3 degrees C, showed no hysteresis but was able
      to modify the shape of ice crystal growth. In the third and fourth analogues,
      mutations of the aspartic acids 1 and 5 to alanine, and asparagines 16 and 27 to
      leucine in the threonine- and valine-substituted analogues did not affect the
      helicity of the polypeptides, but removed the ability to inhibit ice growth.

PMID- 11240144
TI  - Real time fluorescence analysis of the RecA filament: implications of base pair
      fluidity in repeat realignment.
AB  - During recombination, when Escherichia coli RecA mediates annealing across DNA
      repeats, Watson-Crick chemistry can only specify the complementarity of pairing,
      but not the most optimal frame of alignment. We describe that although stochastic
      alignments across poly(dA) and poly(dT) can lead to sub-optimally annealed
      duplexes containing ssDNA gaps/overhangs, the same are realigned into an optimal
      frame by a putative motor activity of RecA [Sen et al. (2000) Biochemistry 39,
      10196-10206]. In the present study, we analyze the nature of realignment
      intermediates in real time, by employing a fluorescent probe, 2-aminopurine
      (2AP), which can not only report the status of RecA on the unstacked duplex, but
      also the fluidity of bases in such a filament. Although known to display a lower
      affinity for duplex DNA, RecA seems to remain functionally associated with these
      sub-optimally aligned repeat duplexes, until the realignment approaches
      completion. Moreover, a comparison of 2AP fluorescence in repeat versus mixed
      sequences indicates that bases in a RecA repetitive DNA filament exhibit higher
      degrees of freedom that might mediate a 'non-planar hydrogen bonding cross talk'
      across the bases on either strand. We discuss a model to explain the mechanistic
      basis of realignment and its implications in signaling the end of homology
      maximization, which triggers RecA fall off.

PMID- 11240145
TI  - Structure determination and by-product profile of the NK(2) receptor antagonist
      nepadutant, a bicyclic glycopeptide.
AB  - We have synthesized and fully characterized the NK(2) receptor antagonist
      nepadutant and its by-products using nuclear magnetic resonance (NMR) and
      restrained molecular dynamics. The agent consists of an active bicyclic
      hexapeptide combined with a sugar residue. Analysis of the high-performance
      liquid chromatogram and the mass spectroscopy spectra yields traces of three by
      products with the same molecular weight as the main product. The conformation of
      the molecules in the bicyclic hexapeptide segment, the active region, is well
      defined, whereas the sugar moiety is disordered. For the peptide region of
      nepadutant and all of its by-products, the NMR observables can be described by a
      single backbone conformation, more specifically a betaI, betaII-turn arrangement.
      The active dipeptide unit Trp-Phe occupies the i+1 and i+2 position of a betaI
      turn. The by-product profile is characterized by different forms of sugars which
      are caused mainly by isomerization in the process of ring opening.

PMID- 11240146
TI  - Genetic and functional linkage of Kir5.1 and Kir2.1 channel subunits.
AB  - We have identified several cDNAs for the human Kir5.1 subunit of inwardly
      rectifying K(+) channels. Alternative splicing of exon 3 and the usage of two
      alternative polyadenylation sites contribute to cDNA diversity. The hKir5.1 gene
      KCNJ16 is assigned to chromosomal region 17q23.1-24.2, and is separated by only
      34 kb from the hKir2.1 gene (KCNJ2). In the brain, Kir5.1 mRNA is restricted to
      the evolutionary older parts of the hindbrain, midbrain and diencephalon and
      overlaps with Kir2.1 in the superior/inferior colliculus and the pontine region.
      In the kidney Kir5.1 and Kir2.1 are colocalized in the proximal tubule. When
      expressed in Xenopus oocytes, Kir5.1 is efficiently targeted to the cell surface
      and forms electrically silent channels together with Kir2.1, thus negatively
      controlling Kir2.1 channel activity in native cells.

PMID- 11240148
TI  - Innervation of the airways: introduction.

PMID- 11240149
TI  - Airway receptors.
AB  - There are many types of afferent receptor in the airways; at least five in the
      larynx: pressure, drive, cold, irritant and C-fibre; and at least four in the
      trachea and bronchi: slowly and rapidly adapting stretch receptors (SARs and
      RARs), C-fibre receptors, and those in neuroepithelial bodies (NEBs).
      Histologically enough sensory structures have been identified to account for the
      various patterns of afferent activity, but most correlations are poor. For the
      larynx, four or more sensory structures have not definitively been identified
      with afferent discharges and reflex responses. For the trachea and bronchi, only
      SARs have been clearly identified morphologically and physiologically. The
      reflexes and afferent discharges from RARs and C-fibre receptors are fairly
      clear, some at least of the sensory terminals lie in the epithelium, but receptor
      complexes have not been mapped out. Nerves in NEBs have been identified, but not
      their local and central reflex actions.

PMID- 11240150
TI  - An overview of the anatomy and physiology of slowly adapting pulmonary stretch
      receptors.
AB  - Since the original work of by Hering and Breuer in 1868 numerous studies have
      demonstrated that slowly adapting pulmonary stretch receptors (SARs) are the lung
      vagal afferents responsible for eliciting the reflexes evoked by moderate lung
      inflation. SARs play a role in controlling breathing pattern, airway smooth
      muscle tone, systemic vascular resistance and heart rate. Both anatomical and
      physiological studies support the contention that SARs, by their close
      association with airway smooth muscle, continuously sense the tension within the
      myoelastic components of the airways caused by lung inflation, smooth muscle
      contraction and/or tethering of small intrapulmonary airways to the lung
      parenchyma. In addition, intrapulmonary SAR discharge activity is sensitive to
      changes in P(CO2) within the physiological range. Despite this extensive
      characterization of SARs, their role in determining breathing pattern and airway
      tone in individuals with respiratory diseases is only recently being appreciated.

PMID- 11240152
TI  - Afferent properties and reflex functions of bronchopulmonary C-fibers.
AB  - Bronchopulmonary C-fiber afferents are characterized by their distinct
      sensitivity to chemical stimuli in the airways or pulmonary circulation.
      Responses evoked by activating these afferents are mediated by both central
      reflex pathways and by local or axon reflexes involving the release of
      tachykinins from sensory endings. Bronchopulmonary C-fiber stimulation reflexly
      reduces tidal volume and increases respiratory rate, constricts the airways,
      increases mucus secretion in the airways, and is associated with coughing.
      Cardiovascular effects include bradycardia, a fall in cardiac output, and
      bronchial vasodilation that increases airway blood flow despite systemic
      hypotension. In animals, C-fiber stimulation inhibits skeletal muscle activity,
      and in humans, is accompanied by burning and choking sensations in the throat and
      upper chest. Recent studies have identified additional physiologic and
      pharmacologic stimuli to these afferents, such as hydrogen ions, adenosine,
      reactive oxygen species, and hyperosmotic solutions. Furthermore, increasing
      evidence indicates that the excitability of these afferents is enhanced by the
      local release of certain autocoids (e.g. PGE2) during airway inflammation. These
      findings further indicate that vagal C-fiber endings in the lungs and airways
      play an important role in regulating the cardiopulmonary functions under both
      normal and abnormal physiologic conditions.

PMID- 11240151
TI  - Reflexes from airway rapidly adapting receptors.
AB  - Rapidly adapting receptors (RARs) occur throughout the respiratory tract from the
      nose to the bronchi. They have thin myelinated nerve fibres, an irregular
      discharge and adapt rapidly to a maintained volume stimulus, but often slowly to
      a chemical stimulus. They are polymodal, responding to mechanical and chemical
      irritant stimuli, and to many inflammatory and immunological mediators. RARs show
      very varied sensitivities to different stimuli, and diverse reflex responses.
      Those in the larynx are usually called 'irritant' receptors. They probably cause
      cough, the expiration reflex and other laryngeal reflexes: cardiovascular, mucus
      secretion, bronchoconstrictor and laryngoconstrictor. Those in the trachea and
      larger bronchi are very mechanosensitive; they cause cough, bronchoconstriction
      and airway mucus secretion. Those in the larger bronchi are more chemosensitive;
      they may cause cough, but also stimulate hyperventilation, augmented breaths,
      mucus secretion, bronchoconstriction and laryngeal closure. Most of the stimuli
      to RARs also affect other airway receptors, especially those with C-fibre
      afferents, and the total reflex response will be the additive affect of all these
      reflexes.

PMID- 11240153
TI  - Central nervous pathways and control of the airways.
AB  - Neural control of airway muscles and secretions is predominantly by excitatory
      parasympathetic and non-adrenergic, non-cholinergic innervations (excitatory
      and/or inhibitory depending on the species). Functionally distinct afferents
      effecting airway reflexes terminate in different but overlapping parts of the
      nucleus tractus solitarius, where integration of simultaneously evoked reflex
      responses occurs. Parasympathetic preganglionic neurones are located in the
      dorsal vagal nucleus and nucleus ambiguus, which also contains upper airway
      motoneurones. These output neurones receive inputs from the central respiratory
      network which modify the effectiveness of reflex activity. This is particularly
      important since many afferents evoking airway reflexes concurrently modify
      respiratory drive. Thus, their effect on the outflow is twofold, a direct reflex
      effect and an indirect respiratory action and these may facilitate or antagonise
      one another. Although there is reflex control of individual motor outflows, in
      some defined situations, e.g. swallowing and coughing a stereotypical pattern of
      motor outflow is evoked. The neural mechanisms underlying these aspects of airway
      control are discussed.

PMID- 11240154
TI  - Ion channels in airway afferent neurons.
AB  - Action potentials initiated at the peripheral terminal of an afferent nerve are
      conducted to the central nervous system therein causing release of
      neurotransmitters that excite secondary neurons in the brain stem or spinal cord.
      Various chemicals, extremes in osmolarity and pH as well as mechanical stimuli
      are sensed by primary afferent nerves that innervate the airways. The processes
      leading to excitation of afferent nerve endings, conduction of action potentials
      along axons, transmitter secretion, and neuronal excitability are regulated by
      ions flowing through channels in the nerve membrane. Voltage-gated ion channels
      selective for K+ and Na+ ions allow the generation and conduction of action
      potentials and along with families of ion channels selective for other ions such
      as Ca2+ or Cl- are thought to play distinctive roles in regulating neuronal
      excitability and transmitter secretion. Here we discuss, in general terms, the
      roles played by various classes of ion channels in the activation,
      neurotransmitter secretion and excitability of primary afferent neurons.

PMID- 11240155
TI  - Transmission in autonomic ganglia.
AB  - The activity of airway smooth muscle, glands and vasculature is under tonic
      control by the autonomic nervous system. Information regarding the function and
      state of the airway (e.g. blood flow, temperature, oxygen levels, movement,
      irritants, inflammation, etc.) is relayed to the central nervous system (CNS) in
      the form of action potentials carried by sensory nerves. This input is integrated
      at many levels in the CNS and this information is ultimately transformed into
      coded action potentials carried by various preganglionic nerve pathways from the
      CNS to peripheral clusters of neurons referred to as autonomic ganglia. In the
      autonomic ganglia the CNS-derived action potentials cause the release of
      neurotransmitter(s) at a synapse between the preganglionic nerve terminal and the
      principal ganglion neuron. The fact that synaptic transmission exists makes the
      ganglion neuron the final site of integration in this complex reflex pathway.
      Whether this transmission of information from the CNS occurs, by activating the
      autonomic ganglion neuron and consequently the effector organ, depends on
      neurochemical, anatomical, and electrophysiological factors within the ganglion
      that is the subject of this review.

PMID- 11240156
TI  - Neural regulation of airway smooth muscle tone.
AB  - Airway smooth muscle is innervated by sympathetic and parasympathetic nerves.
      When activated, airway nerves can markedly constrict bronchi either in vivo or in
      vitro, or can completely dilate a precontracted airway. The nervous system
      therefore plays a primary role in regulating airway caliber and its dysfunction
      is likely to contribute to the pathogenesis of airways diseases. The predominant
      contractile innervation of airway smooth muscle is parasympathetic and
      cholinergic in nature, while the primary relaxant innervation of the airways is
      comprised of noncholinergic (nitric oxide synthase- and vasoactive intestinal
      peptide-containing) parasympathetic nerves. These parasympathetic nerves are
      anatomically and physiologically distinct from one another and differentially
      regulated by reflexes. Sympathetic-adrenergic nerves play little if any role in
      directly regulating smooth muscle tone in the human airways. Activation of airway
      afferent nerves (rapidly adapting receptors, C-fibers) can evoke increases in
      airway smooth muscle parasympathetic nerve activity, or decreases in
      parasympathetic nerve activity (through activation of slowly adapting receptors).
      Extrapulmonary afferents can also modulate nerve mediated regulation of airway
      smooth muscle tone. In guinea pigs and rats, peripheral activation of tachykinin
      containing airway afferent nerves evokes bronchospasm via release of substance P
      and neurokinin A. This effect of airway afferent nerve activation appears to be
      unique to guinea pigs and rats. The actions and interactions between the
      components of airway innervation are discussed.

PMID- 11240157
TI  - Motor control of airway goblet cells and glands.
AB  - Activation of nerves increases airway mucus secretion. The mucus derives from
      submucosal glands and epithelial goblet cells. Depending upon species and airway
      level, innervation comprises parasympathetic (cholinergic), sympathetic
      (adrenergic) and 'sensory-efferent' pathways. In all species studied, cholinergic
      mechanisms predominate, particularly in human airways. Muscarinic M3 receptors on
      the secretory cells mediate the cholinergic response. Tachykinins (substance P
      and neurokinin A) mediate the sensory-efferent response, acting via tachykinin
      NK1 receptors. Endogenous mechanisms regulate the magnitude of neurogenic
      secretion, including enzymes (degrade neurotransmitters), nitric oxide (NO) and
      vasoactive intestinal peptide (VIP) (regulate stimulated secretion), and
      muscarinic M2 autoreceptors (inhibit acetylcholine release). Exogenous opioids
      also inhibit neurogenic secretion prejunctionally. Both VIP and opioids act by
      opening large conductance, calcium-activated potassium (BK(Ca)) channels. Present
      understanding of neural control of mucus secretion in animal airways requires
      translation into human data. This information should lead to rational development
      of drugs for bronchial diseases in which neurogenic mucus hypersecretion
      contributes to pathophysiology, including chronic bronchitis and asthma.

PMID- 11240158
TI  - Neurogenic inflammation in the airways.
AB  - Release of neuropeptides, including tachykinins and calcitonin gene-related
      peptide, from sensory nerves via an axon or local reflex may have inflammatory
      effects in the airways. This neurogenic inflammation may be initiated by
      activation of sensory nerves by inflammatory mediators and irritants. Neurogenic
      inflammation is well developed in rodents and may contribute to the inflammatory
      response to allergens, infections and irritants in animal models. However, the
      role of neurogenic inflammation in airway inflammatory diseases, such as asthma
      and COPD is still uncertain as there is little direct evidence for the
      involvement of sensory neuropeptides in human airways. Initial clinical studies
      using strategies to block neurogenic inflammation have not been encouraging, but
      it is important to study more severe forms of airway disease in more prolonged
      studies in the future to explore the role of neurogenic inflammation.

PMID- 11240159
TI  - Age-associated changes in gene expression patterns in the duodenum and colon of
      rats.
AB  - In humans, decreased intestinal motility, compromised nutritional status and
      increased risk of colon cancer are commonly associated with aging. Here, we used
      the cDNA microarray analysis to detect age-associated changes in duodenal and
      colonic gene expression in male Fischer 344 rats. The primary finding of this
      study is that the magnitude and direction of age-associated changes in gene
      expression differs in the colon and duodenum. In the colon, 56 genes showed
      altered expression, whereas expression of only 25 genes was altered in the
      duodenum. The magnitude of change was greater in the colon than in the duodenum.
      The direction of change also differed; in the aged colon, expression of 51 genes
      increased and only five genes decreased. In contrast, in the aged duodenum, only
      seven genes increased, whereas 18 genes decreased in expression. In the duodenum
      of aged rats, expression of genes involved in ATP-generating pathways is
      decreased. In contrast, in the colon of aged rats, expression of genes involved
      in energy generating pathways and in lipid oxidation is increased. In addition,
      in the aging colon, an increased expression of genes that show an aberrant
      regulation in colon cancer, including CD44, ras, and maspin is observed.
      Collectively, these findings provide clues to molecular events that may be
      related to compromised intestinal function and the high incidence of colon cancer
      in the aged population.

PMID- 11240160
TI  - Age-dependent IGF-1 regulation of gene transcription of Ca2+ channels in skeletal
      muscle.
AB  - In the present work, we investigated whether IGF-1 regulates the transcription of
      the genes encoding the L-type Ca2+ channel (DHPR) channel and RyR1 in young adult
      and senescent mice. To this end, a transgenic mouse model overexpressing IGF-1
      exclusively in skeletal muscle (S1S2) was studied at different ages and the
      results were compared with wild type age-matched mice (FVB). We found that
      ribosomal RNA expression did not change significantly either with age or IGF-1
      according to ribonuclease protection and nuclear run-on transcription assays.
      Transgenic overexpression of IGF-1 resulted in marked increases in skeletal
      muscle DHPR alpha(1S) and RyR1 mRNA in young and old mice and in enhanced DHPR
      alpha(1S) nuclear transcription in skeletal muscles from young mice when
      normalized to 28S ribosomal RNA. These results support the concept that IGF-1
      regulates the expression of DHPR by modulating DHPR alpha(1S) nuclear
      transcription.

PMID- 11240161
TI  - Glucagon and vasopressin V1a receptor signaling in hepatocytes from aging rats.
AB  - Glucose tolerance is reduced with age. The relationship between this change in
      glucose homeostasis and signaling of glucagon and vasopressin V1a receptors was
      investigated in hepatocytes isolated from 10- and 30-month-old female WAG/Rij
      rats. Binding capacity of hepatocytes for 125I glucagon and 3H vasopressin
      increased 2- and 1.8-fold, respectively, between 10 and 30 months. Intracellular
      cAMP accumulation induced by glucagon was 40% greater in hepatocytes of aging
      rats than of adults, although EC(50) were similar in the two groups. Conversely,
      phosphodiesterases activity and nucleotides leakage out of the cells were
      unchanged with age. The rise in intracellular calcium consecutive to the
      stimulation of V1a receptor was comparable in adult and senescent animals.
      Finally, glucose release by hepatocyte suspensions was greater in senescent than
      in adult animals in absence as in presence of glucagon. These experiments suggest
      that increase in glucagon receptor expression and cAMP generation would
      contribute to the impaired glucose tolerance characteristic of the aging process.

PMID- 11240162
TI  - Endogenous glutamate-taurine interaction in striatum and nucleus accumbens of the
      freely moving rat: studies during the normal process of aging.
AB  - Using microdialysis, the effects of endogenous glutamate on extracellular
      concentrations of taurine, in striatum and nucleus accumbens of the awake rat
      during the normal process of aging were investigated. The glutamate uptake
      inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) was perfused through
      the microdialysis probe to increase the endogenous concentration of glutamate.
      Young (2-4 months), middle aged (12-14 months), aged (27-32 months) and very aged
      (37 months) male Wistar rats were used. PDC (1, 2 and 4 mM) produced a dose
      related increase of extracellular concentrations of glutamate and taurine in
      striatum and nucleus accumbens in all groups of age. Increases of glutamate, but
      not of taurine, decreased during aging in striatum. In nucleus accumbens there
      were no age-related changes in the increases of glutamate and taurine induced by
      PDC. In all age groups, increases of extracellular taurine were significantly
      correlated with increases of extracellular glutamate. However, when these taurine
      glutamate correlations for all groups of age were compared, no statistical
      differences were found. These results show first that a decrease in the increases
      of glutamate produced by the glutamate reuptake inhibitor in striatum, but not in
      nucleus accumbens, is produced by age; second that glutamate-taurine interaction
      in striatum and nucleus accumbens does not change during the normal process of
      aging.

PMID- 11240163
TI  - Age-related changes in oxidative damage to lipids and DNA in rat skin.
AB  - Skin is a tissue exposed most frequently to oxidative stress from the environment
      in daily life. Age-related changes of oxidative damage and antioxidant enzyme
      activity in the skin were examined in male Fischer 344 rats aged 6 to 30 months.
      The contents of phosphatidylcholine hydroperoxide (PCOOH) and thiobarbituric acid
      reacting substances (TBARS) increased linearly with age. The content of
      cholesterol hydroperoxide increased until 24 months of age and then decreased.
      The content of 8-oxo-2'-deoxyguanosine (8-oxodG) increased gradually with age,
      and was significantly higher at 30 months of age than at 6 months of age.
      Superoxide dismutase activity tended to decrease with age. The activities of
      catalase and glutathione peroxidase showed no changes with age. We examined the
      effect of dietary restriction on the accumulation of oxidative damage in rat
      skin. The increase in PCOOH content in the skin of dietary-restricted rats was
      suppressed until 30 months of age. The TBARS and cholesterol hydroperoxide
      contents in the skin of dietary-restricted rats were significantly lower than in
      the skin of ad libitum-fed rats, while the 8-oxodG content was somewhat lower in
      the dietary-restricted rats than the ad libitum-fed rats. These results indicate
      that oxidative damage to the lipids and DNA in rat skin increases with age and
      that dietary restriction delays the accumulation of oxidative damage in skin.

PMID- 11240166
TI  - The future of radiosurgery: radiobiology, technology, and applications.

PMID- 11240164
TI  - Effect of the degree of fatty acid unsaturation of rat heart mitochondria on
      their rates of H2O2 production and lipid and protein oxidative damage.
AB  - Previous comparative studies have shown that long-lived animals have lower fatty
      acid double bond content in their mitochondrial membranes than short-lived ones.
      In order to ascertain whether this trait protects mitochondria by decreasing
      lipid and protein oxidation and oxygen radical generation, the double bond
      content of rat heart mitochondrial membranes was manipulated by chronic feeding
      with semi-purified AIN-93G diets rich in highly unsaturated (UNSAT) or saturated
      (SAT) oils. UNSAT rat heart mitochondria had significantly higher double bond
      content and lipid peroxidation than SAT mitochondria. They also showed increased
      levels of the markers of protein oxidative damage malondialdehyde-lysine, protein
      carbonyls, and N(e)-(carboxymethyl)lysine adducts. Basal rates of mitochondrial
      oxygen radical generation were not modified by the degree of fatty acid
      unsaturation, but the rates of H2O2 generation stimulated by antimycin A were
      higher in UNSAT than in SAT mitochondria. These results demonstrate that
      increasing the degree of fatty acid unsaturation of heart mitochondria increases
      oxidative damage to their lipids and proteins, and can also increase their rates
      of mitochondrial oxygen radical generation in situations in which the degree of
      reduction of Complex III is higher than normal. These observations strengthen the
      notion that the relatively low double bond content of the membranes of long-lived
      animals could have evolved to protect them from oxidative damage.

PMID- 11240167
TI  - Olfactory groove meningioma: surgical techniques and pitfalls.

PMID- 11240168
TI  - History of the extradural neural axis compartment.

PMID- 11240169
TI  - Brain tissue PO(2), PCO(2), and pH during cerebral vasospasm.
AB  - BACKGROUND: The purpose of the present study was to assess brain tissue
      monitoring for detection of ischemia due to vasospasm in aneurysmal subarachnoid
      hemorrhage (SAH) patients. METHODS: After obtaining informed consent, a burr hole
      was made in 10 patients and a Neurotrend 7 probe was inserted ipsilateral to the
      region of SAH. In eight patients the probe was inserted during surgery for
      clipping the aneurysm and in two patients the probe was inserted in the
      neurosurgery ICU. Brain tissue gases and pH were collected over 6-hour periods
      for 7 to 10 days until the termination of monitoring. The onset of vasospasm was
      confirmed by angiography and xenon computed tomography (Xe/CT) cerebral blood
      flow studies. RESULTS: Seven patients did not develop vasospasm during monitoring
      and were considered as controls. In this group, brain tissue oxygen pressure
      (PO(2)) remained above 20 mmHg, carbon dioxide pressure (PCO(2)) stabilized at 40
      mmHg and pH remained between 7.1 and 7.2. In three patients who developed
      vasospasm during monitoring, PO(2) was not different from the control group.
      However, PCO(2) increased to 60 mmHg and pH decreased to 6.7 (p < 0.001).
      CONCLUSION: In this study, patients with SAH who developed vasospasm had
      significantly lower brain tissue pH and higher PCO(2) compared to controls.
      However, there was no significant change in PO(2) levels associated with
      vasospasm. Brain tissue monitoring can provide an indication of ischemia during
      vasospasm.

PMID- 11240172
TI  - Horner's syndrome after carotid artery stenting: case report.
AB  - BACKGROUND: Angioplasty and stenting of various lesions of the carotid artery is
      gaining in popularity. Our knowledge of the efficacy and limitations of this
      promising technology is incomplete. Although Horner's syndrome and its variants
      have been described after traumatic, spontaneous, or surgical carotid dissection,
      it has not been reported after carotid artery stenting. CASE DESCRIPTION: A 36
      year-old woman presented with left neck and ear pain and a 3-year history of
      rushing noises in her left ear. Angiography demonstrated evidence of dissection
      of the left internal carotid artery at the skull base with a pseudoaneurysm. The
      pseudoaneurysm was treated with a 6-mm diameter self-expanding stent in a 4-mm
      diameter left internal carotid artery. A few hours later, she developed partial
      Horner's syndrome with a subtle ipsilateral ptosis and miosis without anhidrosis.
      Angiography performed on the next day did not demonstrate further dissection or
      aneurysm growth but did show distention of the artery wall because of the stent.
      She did not develop any further sequelae. CONCLUSION: This case suggests that
      stretching of the artery wall may result in stretching of surrounding structures.
      The sympathetic fibers surrounding the internal carotid artery are clearly
      sensitive to this degree of stretch. Possible complications associated with
      stretch injury must be considered when choosing the stent diameter.

PMID- 11240173
TI  - Iatrogenic acute subdural hematoma due to drainage catheter.
AB  - BACKGROUND: Insertion of a catheter for drainage of a cavity is a routine step in
      many surgical practices. In neurosurgery, catheters are commonly placed in the
      subdural, subgaleal, or epidural spaces to prevent haematoma formation. CASE
      DESCRIPTION: We present three cases of iatrogenic acute subdural hematoma. These
      were all related to the drainage catheters. In the first case, a subgaleal
      redivac suction catheter was used after craniotomy for brain abscess. The other
      two patients had ordinary ventricular catheters placed in the subdural space
      after burr hole drainage of chronic subdural hematoma. The drainage catheter was
      removed on postoperative day 5 in the first case and two days after the initial
      operation in the other two cases. Shortly after the removal of the drains, the
      conditions of the patients deteriorated rapidly due to the development of acute
      subdural hematoma. CONCLUSION: Although they are extremely uncommon, life
      threatening complications related to a drainage catheter are a real possibility.
      Therefore, the procedure should not be taken lightly.

PMID- 11240175
TI  - Ophthalmoplegia resulting from an intraorbital hematoma.
AB  - BACKGROUND: A case is described in which an intraorbital hematoma was found to
      complicate recovery from attempted aneurysm clipping 5 days into the
      postoperative period. The etiology, management, and complication avoidance are
      discussed. CASE DESCRIPTION: Five days after attempted surgical clipping of an
      internal carotid artery aneurysm via a frontotemporal craniotomy with orbital
      osteotomy, a patient underwent coiling of the aneurysm. Shortly after the
      endovascular procedure, the patient developed exophthalmos and ophthalmoplegia
      involving the right side followed by decline in her level of consciousness. An
      emergency computed tomography (CT) scan revealed an epidural hematoma with
      intraorbital extension. After evacuation of the hematoma, the patient recovered
      extraocular function and returned to her baseline mental status. CONCLUSION:
      Exophthalmos and ophthalmoplegia in a patient recovering from cranial surgery
      using skull base techniques warrants immediate attention, especially after
      endovascular procedures. Delay in intervention may result in loss of neurologic
      function or life. The authors discuss the relevant literature and management of
      this uncommon complication.

PMID- 11240177
TI  - Intracranial extension of a dermatofibrosarcoma protuberans of the scalp: a case
      report with brief review of literature.

PMID- 11240178
TI  - Migration of an intraspinal schwannoma documented by intraoperative ultrasound:
      case report.
AB  - BACKGROUND: Tumors of the cauda equina may shift with positioning on the
      operating table. Accurate localization at surgery is important to facilitate
      appropriate laminectomy and durotomy. CASE DESCRIPTION: We report a case of a 28
      year-old man with a schwannoma of the cauda equina at L4 on preoperative MRI.
      Intraoperative ultrasound revealed that the tumor had migrated cephalad, and was
      now located at L3. CONCLUSION: Intraoperative ultrasound is a valuable technique
      in localization of tumors of the cauda equina.

PMID- 11240179
TI  - Syringe needle located deep in the brain: image-guided removal.
AB  - BACKGROUND: Removal of a thin but long foreign body lodged in the deep brain
      tissue may need special technique to remove it without causing major injury. We
      report a special technique for the safe, elective removal of such objects. CASE
      DESCRIPTION: A 5-year-old boy presented following mild head trauma; he was
      asymptomatic and physical examination revealed an intact scalp and no
      neurological deficit. The incidental presence of a 3.4 cm-long syringe needle in
      the right frontal region was noted on the skull radiographs. Cranial computed
      tomography (CT) scan showed the deeper end of the needle in the right caudate
      head and the superficial end at a depth of 3.5 cm from the cortical surface. Burr
      hole surgery was performed under general anesthesia employing a Fisher
      stereotactic frame and continuous biplanar guidance from the image intensifiers.
      The superficial end of the needle was clasped with an endoscopy biopsy forceps,
      allowing removal of the needle via the least traumatic route. The child had an
      uneventful recovery. Follow-up magnetic resonance imaging at 6 months did not
      reveal any abnormality. CONCLUSIONS: The two-dimensional biplanar image-guided
      stereotactic technique allowed safe removal of a long foreign body from a deep
      brain location with minimal trauma to the brain.

PMID- 11240181
TI  - A visit to Hungary: a solemn occasion.

PMID- 11240182
TI  - Effect of reaction conditions on phenol removal by polymerization and
      precipitation using Coprinus cinereus peroxidase.
AB  - The quantitative relationships between removal efficiency of phenol and reaction
      conditions were investigated using Coprinus cinereus peroxidase. The most
      effective ratio of hydrogen peroxide to phenol was nearly 1/1 (mol/mol) at an
      adequate enzyme dose. 12.2 U of the enzyme was needed to remove 1 mg of phenol
      when our peroxidase preparation was used. At an insufficient peroxidase dose, the
      optimum pH value was 9.0, and lowering the reaction temperature led to the
      improvement of removal efficiency. At an excess peroxidase dose, almost 100%
      removal of phenol was obtained over a wide range of pH (5-9) and temperature (0
      60 degrees C). Despite the presence of culture medium components, it was shown
      that Coprinus cinereus peroxidase had the same phenol polymerization performance
      as horseradish peroxidase or Arthromyces ramosus peroxidase.

PMID- 11240183
TI  - Investigation of the role of 3-hydroxyanthranilic acid in the degradation of
      lignin by white-rot fungus Pycnoporus cinnabarinus.
AB  - An aminophenol, 3-hydroxyanthranilic acid (3-HAA), has been proposed to play
      important roles in lignin degradation. Production of 3-HAA in Pycnoporus
      cinnabarinus was completely inhibited by a combination of tryptophan and S-(2
      aminophenyl)-L-cysteine S,S-dioxide (APCD) while the fungus grew well and
      produced high amounts of laccase. The biosynthesis of 3-HAA is mainly through the
      metabolism of tryptophan in the kynurenine pathway. A minor pathway for 3-HAA
      synthesis is through the hydroxylation of anthranilic acid during the
      biosynthesis of tryptophan in the shikimic acid pathway. Through UV irradiation
      of wild-type P. cinnabarinus (WT-Pc) spores, a 3-HAA-less mutant was produced.
      Both WT-Pc, under the inhibitory culture condition, and the 3-HAA-less mutant
      were found to degrade lignin in unbleached kraft pulp as efficiently as the WT
      Pc, which unambiguously demonstrated that 3-HAA does not play an important role
      in the fungal degradation of lignin.

PMID- 11240184
TI  - Molecular weight distribution and structural characteristics of polymers obtained
      from acid soluble lignin treated by oxidative enzymes.
AB  - Brown precipitates were obtained by polymerization of low molecular weight lignin
      fragments contained in a model effluent. Polymerization reactions were initiated
      by potato-polyphenoloxidase (PPO) or horseradish peroxidase/H(2)O(2) system
      (HRP/H(2)O(2)). The insolubilization processes occurred after a molecular weight
      increase of the lignin, as shown by gel permeation chromatography (GPC). The
      effect of reaction time, pH and amount of soluble lignin per unit of enzyme
      activity on the molecular weight distribution was evaluated for PPO-initiated
      reactions. For HRP-initiated system the amount of H(2)O(2) per unit of enzyme
      activity was also evaluated. Chemical characterization of the macromolecules
      obtained under optimized conditions and the soluble lignin fragments present in
      the effluent suggests that the polymerization reactions occur by oxidative
      cleavage of alpha-beta unsaturated bonds of the soluble lignin fragments.
      Methoxyl group analysis showed that p-hydroxycoumaryl units were preferentially
      oxidized by PPO. In contrast, HRP oxidized preferentially guaiacyl and siringyl
      units giving more condensed polymers.

PMID- 11240185
TI  - Factorial designs combined with the steepest ascent method to optimize serum-free
      media for CHO cells.
AB  - A serum free medium for recombinant CHO NTHU 108 cell growth and fusion protein
      (CD20 linked to a human IgG-Fc gamma4 fragment) synthesis were systematically
      developed using factorial designs combined with the steepest ascent method.
      Experimental results indicate that the optimal composition of serum replacement
      for specific fusion protein production was 1% SITE (selenium, insulin,
      transferrin, ethanolamine), 0.3 g/L yeast extract, and 0.09% linoleic acid-BSA.
      Cell growth and fusion protein production of the adapted CHO NTHU 108 cultured in
      Iscove's modified Dulbecco's medium supplemented with these serum substitutes
      were comparable to those in the Ex-Cell 301 commercial serum-free medium. These
      serum substitutes can also promote CHO cell growth and fusion protein production
      in nine kinds of commercial media. The low protein content of the developed
      medium facilitates downstream processing and product purification.

PMID- 11240186
TI  - Novel methods to estimate the enantiomeric ratio and the kinetic parameters of
      enantiospecific enzymatic reactions.
AB  - 1The Enantiomeric Ratio (E) of the enzyme, acting as specific catalysts in
      resolution of enantiomers, is an important parameter in the quantitative
      description of these chiral resolution processes. In the present work, two novel
      methods hereby called Method I and II, for estimating E and the kinetic
      parameters Km and Vm of enantiomers were developed. These methods are based upon
      initial rate (v) measurements using different concentrations of enantiomeric
      mixtures (C) with several molar fractions of the substrate (x). Both methods were
      tested using simulated "experimental data" and actual experimental data. Method I
      is easier to use than Method II but requires that one of the enantiomers is
      available in pure form. Method II, besides not requiring the enantiomers in pure
      form shown better results, as indicated by the magnitude of the standard errors
      of estimates. The theoretical predictions were experimentally confirmed by using
      the oxidation of 2-butanol and 2-pentanol catalyzed by Thermoanaerobium brockii
      alcohol dehydrogenase as reaction models. The parameters E, Km and Vm were
      estimated by Methods I and II with precision and were not significantly different
      from those obtained experimentally by direct estimation of E from the kinetic
      parameters of each enantiomer available in pure form.

PMID- 11240187
TI  - Preparation and catalytic performance of surfactant-manganese peroxidase-Mn(II)
      ternary complex in organic media.
AB  - A novel preparation method for surfactant-MnP-Mn(II) ternary complex utilizing
      water-in-oil emulsions has been developed. The surfactant-MnP complex was
      spectroscopically characterized, strongly suggesting that the heme environment of
      the surfactant-MnP complex in benzene is identical to that of native MnP in the
      aqueous buffer. o-Phenylenediamine oxidation catalyzed by the surfactant-MnP
      Mn(II) ternary complex was performed in benzene. The ternary complex efficiently
      catalyzed the oxidation, and the complex was catalytically stable. Kinetic
      experiments revealed that the reaction mechanism was as follows: MnP is oxidized
      by H(2)O(2) and the oxidized intermediate catalyzes the oxidation of Mn(II) to
      Mn(III) and the latter, after complexed with malonate, readily oxidizes o-PDA
      inside the complex. Thus, the organic substrate o-PDA, but not Mn(III), shuttled
      between the surfactant-MnP-Mn(II) ternary complex and organic solvent.

PMID- 11240188
TI  - Novel route for the resolution of both enantiomers of dropropizine by using oxime
      esters and supported lipases of Pseudomonas cepacia.
AB  - Resolution of (R)- and (S)-dropropizine which is an antitussive and central
      sedative therapeutic agent in high optical and chemical yields was achieved by
      lipases of Pseudomonas cepacia supported on ceramic particles (lipase PS-C) and
      on diatomite (lipase PS-D) with oxime esters in organic solvents. The influence
      of several factors (lipase source, structural variations in oxime esters, the
      amount of lipase and its recyclability) on the enantioselectivity have been
      investigated. Different properties were used to describe the solvents, namely the
      hydrophobicity (quantified by log P) and the dielectic constant (epsilon). This
      enzymatic acylation using oxime esters was significant as only (S)-dropropizine
      and (R)-dropropizine monoacetate was obtained. (R)-Dropropizine monoacetate was
      chemically hydrolyzed to obtain (R)-dropropizine. The highest enantioselectivity
      was observed when O-acetyl benzophenone oxime was used. This enzymatic resolution
      provides a versatile method for getting the pure enantiomers of dropropizine by
      effectively optimizing the various reaction parameters.

PMID- 11240189
TI  - Effect of temperature on the microaerophilic metabolism of Pachysolen
      tannophilus.
AB  - Xylitol production by Pachysolen tannophilus from detoxified hemicellulose
      hydrolysate was investigated under microaerophilic conditions at temperature
      ranging from 20 to 40 degrees C. A carbon balance previously proposed to study
      the influence of pH was used in this work to evaluate the amounts of carbon
      source (xylose) utilised in competitive metabolic ways: reductive production of
      xylitol, ethanol fermentation and respiration. At pH = 5.5 more than 83% of
      xylose was reduced to xylitol at 25 < T < 30 degrees C, whereas respiration
      became the main process at low temperature (71.1% at 20 degrees C). At high
      temperature, on the other hand, all three processes took place at comparable
      rate, consuming at 40 degrees C nearly the same percentage of carbon source (33
      35%). Finally, the maximum values of volumetric productivity calculated at
      variable temperature were used to estimate the main thermodynamic parameters of
      both xylitol production (Deltah* = 105.4 kJ mol(-1); Deltas* = -13.2 J mol(-1) K(
      1)) and thermal deactivation (Deltah*(D) = 210.5 kJ mol(-1); Deltas*(D) = 3.63 J
      mol(-1) K(-1)).

PMID- 11240190
TI  - The application of foaming for the recovery of Surfactin from B. subtilis ATCC
      21332 cultures.
AB  - Foaming, a proficient method for the recovery of surface active solutes from
      dilute solutions, was successfully applied for the concentration of the
      lipopeptide biosurfactant Surfactin from B. subtilis ATCC 21332 cell culture
      broths. Foaming was only partially successful in concentrating Surfactin when
      applied as a separate semi-batch unit downstream of the cell culture stage.
      Surfactin partitioned strongly into the foam during the latter stages of the semi
      batch process, where enrichments of over 50 could be obtained. However,
      simultaneous high enrichments and recoveries of Surfactin could not be obtained
      as the majority of Surfactin (around 70% of the total recovered) was produced at
      a low concentration during the early stages of foaming. Foam fractionation was
      considered for both cell free and cell containing broths; the presence of cells
      increased the foamability of the solution and therefore yielded more dilute
      Surfactin preparations. More favourable recovery and enrichment of Surfactin
      occurred when foaming was integrated with the cell culture stage. The use of low
      stirrer speeds was essential in producing foam at a controlled rate. By
      collecting fractions of the foam produced between 10 and 30 hours, from systems
      stirred at 166 and 146 rpm, a highly concentrated Surfactin extract could be
      obtained. The Surfactin concentration in the foam was 1.22 and 1.67 g l(-1)
      respectively, which represented enrichments and percent recoveries of over 60.
      This study points to the utility of foaming as a method for the recovery of
      surface-active fermentation products, particularly when used in an integrated
      production/recovery system.

PMID- 11240191
TI  - Ultrafiltration membrane reactors for enzymatic resolution of amino acids: design
      model and optimization.
AB  - In this paper the possibility of continuous resolution of DL-phenylalanine,
      catalyzed by L-aminoacylase in a ultrafiltration membrane reactor (UFMR) is
      presented. A simple design model, based on previous kinetic studies, has been
      demonstrated to be capable of describing the behavior of the experimental system.
      The model has been used to determine the optimal experimental conditions to carry
      out the asymmetrical hydrolysis of N-acetyl-DL-phenylalanine.

PMID- 11240192
TI  - Combining solvent engineering and thermodynamic modeling to enhance selectivity
      during monoglyceride synthesis by lipase-catalyzed esterification.
AB  - Monoglyceride synthesis by Rhyzomucor miehei lipase was investigated via direct
      esterification between glycerol (adsorbed onto silica gel) and oleic acid in
      organic solvents. The main difficulty is to avoid the unwanted production of di-
      and tri-glycerides. It was demonstrated that an increase in solvent polarity,
      using mixtures of n-hexane and 2-methyl-2-butanol (2M2B), improves drastically
      the selectivity toward monoglyceride formation. In pure n-hexane, the
      monoglyceride represents only 6 molar % of the total products at the
      thermodynamic equilibrium (34 and 60% for di- and tri-glyceride respectively).
      Use of an equivolume mixture of n-hexane/2M2B enables a product mixture to be
      obtained containing 94% of monoglyceride at equilibrium (2.4 and 0% for di- and
      tri-glyceride respectively). This positive effect is counterbalanced by a
      decrease both in initial velocities and in substrate conversion at thermodynamic
      equilibrium.A modeling, able to predict the three thermodynamic equilibria
      governing the 3 consecutive reactions, based on activity coefficient calculations
      using the UNIFAC model, is proposed. It takes into account both the partition of
      water between solvent and immobilized catalyst, and the partition of glycerol
      between solvent and silica gel. A good correlation with experimental data
      obtained in n-hexane/2M2B mixtures was observed.

PMID- 11240193
TI  - Effect of a range of microbial polysaccharides on the diffusion of manganese ions
      using spatially resolved NMR relaxometry.
AB  - In accordance with the theory of contact exchange, it is hypothesized that the
      presence of negative charge in microbial exopolysaccharides increases the rate of
      cation transport. These typically acidic materials may provide a fast-track for
      the diffusion of nutrient cations through the polymer layer for uptake at the
      organism cell surface. We have measured the diffusion coefficient of a model
      cation, Mn(2+,) through xanthan, de-acetylated xanthan, scleroglucan and chitosan
      using spatially resolved NMR relaxometry. The concentration of Mn(2+) in solution
      was measured by recording the change in the spin-spin (T(2)) relaxation time of
      water (1)H over time in compartments either side of a polymer layer. This
      approach provides a sensitive, in situ, non-invasive method of measuring the rate
      of diffusion of paramagnetic cations through hydrophilic polysaccharides. The
      negatively-charged polysaccharides, xanthan and de-acetylated xanthan, permitted
      a significantly faster rate (2-2.5x) of cation transport compared to the
      uncharged polymer, scleroglucan. The positively-charged polysaccharide chitosan
      reduced the rate of Mn(2+) diffusion to around half the value obtained for
      scleroglucan. These results suggest that the presence and nature of fixed charges
      on the polysaccharide molecule affects the rate of cation transport in accordance
      with the theory of contact exchange. The presence of negative charge on microbial
      exopolysaccharides may thus improve the availability of nutrient cations at the
      organism cell surface.

PMID- 11240194
TI  - Microbial reclamation of shellfish wastes for the production of chitinases.
AB  - Shrimp and crab shell powder (SCSP), prepared by treating shellfish processing
      waste with boiling and crushing, was used as a substrate for isolating
      chitinolytic microorganisms. Three potential strains (E1, J1, and J1-1) were
      isolated and identified as Bacillus cereus, B. alvei, and B. sphaericus,
      respectively. Three extracellular chitinases (FB1, FB2, and FB3) were purified
      from the culture supernatants of Bacillus cereus E1, B. alvei J1, and B.
      sphaericus J1-1, respectively. The molecular weights of FB1, FB2, and FB3 were
      71,000, 71,000, and 65,000, respectively, by SDS-PAGE. The pIs for FB1, FB2, and
      FB3 were 7.1, 7.2, and 7.4, respectively. The optimum pH, optimum temperature, pH
      stability, and thermal stability of FB1 were pH 9, 50 degrees C, pH 7 to 10, and
      70 degrees C; those of FB2 were pH 9, 60 degrees C, pH 5 to 9, and 70 degrees C;
      and those of FB3 were pH 7, 50 degrees C, pH 5 to 9, and 60 degrees C. The
      activities of all enzymes were strongly inhibited by Hg(2+) and completely
      inhibited by glutathione, dithiothreitol, and 2-mercaptoethanol.

PMID- 11240195
TI  - Monitoring of dihydroxyacetone production during oxidation of glycerol by
      immobilized Gluconobacter oxydans cells with an enzyme biosensor.
AB  - A bi-enzymatic biosensor for monitoring of dihydroxyacetone production during
      oxidation of glycerol by bacterial cells of Gluconobacter oxydans is presented.
      Galactose oxidase oxidizes dihydroxyacetone efficiently producing hydrogen
      peroxide, which reacts with co-immobilized peroxidase and ferrocene pre-adsorbed
      on graphite electrode. This mediator-based bi-enzymatic biosensor possesses very
      high sensitivity (4.7 uA/mM in phosphate buffer), low detection limit (0.8 uM,
      signal/noise = 3), short response time (22 s, 95% of steady-state) and broad
      linear range (0.002-0.55 mM in phosphate buffer). The effect of pH, temperature,
      type of buffer, as well as different stabilizers (combinations of a
      polyelectrolyte and a polyol) on the sensor performance were carefully optimized
      and discussed. Dihydroxyacetone produced during a batch conversion of glycerol by
      the pectate-immobilized bacteria in an air-lift reactor was determined by the
      biosensor and by reference spectrophotometric method. Both methods were compared
      and were in a very good correlation. The main advantage of the biosensor is a
      very short time needed for sample analysis (less than 1 min).

PMID- 11240196
TI  - Modulation of lipase properties in macro-aqueous systems by controlled enzyme
      immobilization: enantioselective hydrolysis of a chiral ester by immobilized
      Pseudomonas lipase.
AB  - Lipase from Pseudomonas fluorescens (PFL) has been immobilized by using different
      immobilization protocols. The catalytic behavior of the different PFL derivatives
      in the hydrolytic resolution of fully soluble (R,S) 2-hydroxy 4-phenyl butanoic
      acid ethyl ester (HPBE) in aqueous medium was analyzed. The soluble enzyme showed
      a significant but low enantioselectivity, hydrolyzing the S isomer more rapidly
      than the R-isomer (E = 7). The enzyme, immobilized via a limited attachment to a
      long and flexible spacer arm, showed almost identical activity and specificity to
      the soluble enzyme. However, other derivatives, e.g. PFL adsorbed on supports
      covered by hydrophobic moieties (octyl, decaoctyl), exhibited significant
      hyperactivation on immobilization (approximately 7-fold). Simultaneously, the
      enantioselectivity of the PFL-immobilized enzyme was significantly improved (from
      E = 7 to E = 80). By using such derivatives, almost pure R ester isomer (e.e. >
      99%) has been obtained after 55% hydrolysis of the racemic mixture of a solution
      of 10% (w/v) (R,S) HPBE. The derivatives could be used for 10 cycles without any
      significant decrease in the activity of the biocatalyst.

PMID- 11240197
TI  - pH dependent conformational and structural changes of xylanase from an
      alkalophilic thermophilic Bacillus sp (NCIM 59).
AB  - The pH induced conformational and structural changes of Xyl II have been
      investigated from the alkalophilic thermophilic Bacillus sp. using kinetic,
      circular dichroism and fluorescence spectroscopy studies. The systematic studies
      on the folding and stability of cellulase-free xylanases are important, since
      their biotechnological applications require them to function under extremes of pH
      and temperature. The Trp fluorescence and the kinetic constants were found
      dependent on the pH. Above pH 8, the enzyme exhibited unfolding transitions as
      revealed by a red shift in the emission maximum as well as decreases in the
      fluorescence intensity. Circular dichroism studies revealed a decrease in the CD
      ellipticity at 222 nm at pH 9 and 10. The reduced catalytic activity of Xyl II at
      alkaline pH is correlated to the pH induced unfolding and ionization or
      protonation of key protein residues. The pH profile of Xyl II showed apparent pK
      values of 5.5 and 7 for the free enzyme and 5.6 and 6.7 for the enzyme-substrate
      complex. The abnormally high pK of 6.7 indicated the participation of a carboxyl
      group present in a non-polar environment. The pH dependence of inactivation
      kinetics of Xyl II with Woodward's reagent K corroborates evidence for the
      presence of a catalytically important carboxyl residue. The sequence alignment
      studies of Xyl II, in combination with kinetic and chemical modification data
      provide strong evidence for the participation of Asp94 in the catalytic function.
      The Xyl II produced from an alkalophilic source, was stable at pH 10 with a
      t(1/2) of 24 h. However, the enzyme exhibited pH optimum at near neutral values,
      which can be explained by the ionization and microenvironment of the active site
      residues.

PMID- 11240198
TI  - Calcite precipitation induced by polyurethane-immobilized Bacillus pasteurii.
AB  - Polyurethane (PU) foam was used to immobilize the whole cell of Bacillus
      pasteurii. The immobilized cells exhibited the rates of calcite precipitation and
      ammonia production as high as those of the free cells. Scanning electron
      micrographs identified the cells embedded in calcite crystals throughout PU
      matrices. Calcite in PU showed little effect on the elastic modulus and tensile
      strength of the polymer, but increased the compressive strengths of concrete
      cubes, whose cracks were remediated with PU-immobilized cells. These observations
      led us to believe that the calcite might remain as a form of precipitation, not
      as a bonding material within the matrices.

PMID- 11240199
TI  - Purification and partial characterization of a cholesterol oxidase from
      Streptomyces fradiae.
AB  - An extracellular cholesterol oxidase from Streptomyces fradiae (PTCC 1121) was
      purified in one step using DEAE-Sepharose. The purified enzyme had a molecular
      weight of 60 KDa. The optimum pH and temperature for activity was found to be 7
      and 70 degrees C, respectively. This cholesterol oxidase was stable in pHs
      between 4-10 at 4 degrees C until 4 h. Thermal stability experiments showed that
      it has high stability and retains its full activity at 50 degrees C for 90 min.
      K(m) value for cholesterol oxidase was obtained to be about 7.06 x 10(-)(5) Mol.

PMID- 11240200
TI  - The potential of positively-charged cellulose sponge for malolactic fermentation
      of wine, using Oenococcus oeni.
AB  - Malolactic fermentation (MLF) is a secondary bioconversion developed in some
      wines involving malic acid decarboxylation. The induction of MLF in wine by
      cultures of free and immobilized Oenococcus oeni cells was investigated. This
      work reports on the effect of surface charges in the immobilization material, a
      recently described fibrous sponge, as well as the pH and the composition of the
      media where cells are suspended. A chemical treatment provided positive charge to
      the sponges (DE or DEAE) and gave the highest cell loadings and subsequent
      resistance to removal. Preculture media to grow the malolactic bacteria before
      the immobilization procedure were also evaluated. We have established favorable
      conditions for growth (Medium of Preculture), suspension solution (Tartrate
      Phosphate Buffer), suspension pH (3.5-5.5) and immobilization matrix (DE or DEAE
      cellulose sponge) to induce MLF in red wine. The use of a semi-continuous system
      permitted a high-efficiency malic acid conversion by 2 x 10(9) cfu sponge(-)(1)
      in at least four subsequent batch fermentations.

PMID- 11240201
TI  - Growth, dye degradation and ligninolytic activity studies on Zimbabwean white rot
      fungi.
AB  - White rot fungi were collected from Chirinda and Chimanimani hardwood forests in
      Zimbabwe and studied with respect to growth temperature optima and dye
      decolorization. Temperature optima were found to vary (between 25-37 degrees C)
      amongst the isolates. The isolates were screened for their ability to degrade the
      polymeric dyes; blue dextran and Poly R478 and the triphenylmethane dyes; cresol
      red, crystal violet and bromophenol blue. Semi-quantitative determination of the
      hydrolytic enzyme activities possessed by the white rot fungi was determined
      using the API ZYM system. Lignin peroxidase (LiP), manganese peroxidase (MnP) and
      laccase activities in the fungi were also determined. No LiP was detected in any
      of the isolates but all isolates showed manganese peroxidase and laccase
      activities. Time related decolorization studies and optimum pH determinations for
      Poly R478 degradation by the isolates were carried out in liquid cultures. The
      most significant rates of Poly R478 decolorization in liquid cultures were found
      with the following isolates: Trametes cingulata, Trametes versicolor, Trametes
      pocas, DSPM95 (a species to be identified), Datronia concentrica and Pycnoporus
      sanguineus.

PMID- 11240202
TI  - A novel chitosan derivative to immobilize alpha-L-rhamnopyranosidase from
      Aspergillus niger for application in beverage technologies.
AB  - alpha-L-rhamnopyranosidase (Rha, EC 3.2.1.40) is an enzyme of considerable
      importance to food technology in increasing the aroma of wines, musts, fruit
      juices and other beverages. The aim of this research is the immobilization of the
      Rha contained in a commercial preparation already used in the winemaking industry
      and purified in the manner described in a previous study [1]. The immobilization
      supports tested were chitin, chitosan and derivatized chitosan, diethylaminoethyl
      chitosan (DE-chitosan) never previously used for this type of application.
      Particularly, on DE-chitosan, the Rha was adsorbed and cross-linked with various
      bifunctional agents (glutaraldehyde, diepoxyoctane, suberimidate and
      carbodiimide), whose best results (immobilization yields and activity) were
      obtained with carbodiimide (EDC) that allowed a reduction in the involvement of
      the enzyme amine groups that are probably important in catalytic mechanism. In
      addition, the use of rhamnose and a succinimide (NHS) during cross-linking
      enhanced the action of the EDC and so increased the immobilization yield and
      activity. The immobilized Rha retained the kinetic parameters (K(m) and V(max))
      of the free enzyme and increased stability. Moreover, this biocatalyst allowed an
      increase in the aroma in a model wine solution containing glicosidic precursors
      with a marked reduction in specificity toward tertiary monoterpenols as compared
      to the free enzyme.

PMID- 11240203
TI  - Production of inulooligosaccharides from chicory extract by endoinulinase from
      Xanthomonas oryzae No. 5.
AB  - Inulooligosaccharides (IOS) production from chicory extract was carried out using
      endoinulinase obtained from a new isolate, Xanthomonas oryzae No. 5. The IOS
      production from chicory extract was maximum when 50 g/liter of chicory extract
      was utilized as the substrate. As the substrate concentration increased, the IOS
      production accordingly decreased probably due to substrate inhibition. For a
      comparative study, enzyme reactions were carried out from pure inulin as
      substrate. Though total IOS contents indicated higher IOS yield with pure inulin
      compared to that of chicory extract, the distribution of inulooligosaccharide
      components between pure inulin and chicory extract was not significantly
      different; i.e. DP5 and higher oligosaccharides are major products in case of
      both chicory extract and pure inulin as substrate. A considerable amount of
      oligofructose (about 30%, w/w), which were originally present in chicory extract,
      resulted in the change of the enzyme kinetics. A reaction pH 7 was found to be
      most suitable for enzyme reaction. The initial reaction rates increased with
      increasing enzyme dosage, although the relative composition of the IOS produced
      remain unchanged.

PMID- 11240204
TI  - Effect of initial glucose concentration and inoculation level of lactic acid
      bacteria in shrimp waste ensilation.
AB  - Fermentation conditions and microorganisms were determined, based on acid
      production, glucose concentration as carbohydrate source. Inoculation levels to
      obtain a stable shrimp waste silage were also determined. Shrimp waste ensilation
      was an efficient method of preservation, allowing the recovery of chitin and
      another added-value products such as pigments, proteins and enzymes. From the
      various lactic acid bacteria tested, Lactobacillus pentosus and Lactobacillus sp.
      (B2) were the best lactic acid producers, although small quantities of acetic
      acid were detected in samples inoculated with Lactobacillus pentosus. Therefore
      B2 was chosen for the analysis of glucose consumption as well as for the
      determination of optimum inoculation levels. The best results were obtained at
      10% (w/w wet basis) and 5% (v/w wet basis) respectively. Presence of starters and
      initial glucose concentration were critical factors in the fermentation of shrimp
      waste. High initial glucose and starter concentrations reduced the time and
      increased the amount of lactic acid produced. The fermentation pattern changed
      during ensilation from hetero to homofermentative. Shrimp waste ensilation
      prevented the growth of spoilage microorganisms keeping their microbial counts
      steady and pH values within the acid region.

PMID- 11240205
TI  - Preservation of the proteolytic activity of a bovine spleen lysosomal-enriched
      extract using various freezing conditions.
AB  - The preservation of the proteolytic activity of a bovine spleen lysosomal
      enriched (BSLE) extract was investigated. The BSLE extract (pH = 5.8), was
      subjected to storage under different conditions: refrigeration at 0 degrees C for
      60 days; freezing at -20 degrees C -either directly or previously frozen in
      liquid nitrogen-, -80 degrees C and in liquid nitrogen; freeze-drying and stored
      at 0 degrees C; and freezing at -20 degrees C or in liquid nitrogen in the
      presence of glycerol and sorbitol as cryoprotectants. Freezing at low
      temperatures (-80 degrees C and in liquid nitrogen) was most effective for
      preserving about 100% of the initial activity of all cathepsins (B, B+L and D),
      as well as the activity of the extract on myofibrils, for two years. Freezing at 
      20 degrees C, on the contrary, led to significant (P < 0.01) losses of activity.
      Freeze-drying was able to preserve cathepsin activity, while it failed to
      maintain activity on myofibrils. Both cryoprotectants sorbitol and glycerol
      significantly (P < 0.01) enhanced enzyme preservation, particularly cathepsin D
      and the activity on myofibrils, even at a freezing temperature of -20 degrees C.

PMID- 11240206
TI  - The effect of ions on the enzymatically induced synthesis of lignin graft
      copolymers.
AB  - The effect of different ions which are constituents of technical lignin
      sulfonates (LS) on chemo-enzymatic graft co-polymerization was determined. The
      application of the iron chelator desferrioxamine in the initial reaction mixture
      revealed that iron impurities of LS which catalyzed a Fenton-like reaction were
      crucial for the initiation of grafting, whereas calcium or chloride ions showed
      no such effect. The addition of laccase (ATCC 11235) to the reaction mixture
      which contained desferrioxamine caused a significantly higher yield compared to
      the control; this indicates a crucial effect of laccase with regard to the
      initiation of copolymerization. The involvement of laccase in the initiation of
      the graft copolymerization was additionally confirmed by the application of low
      molecular weight phenolics instead of LS. In the presence of the lignin-like
      substrates, 3,4-dihydroxybenzoic acid and guaiacol, the rate of the decomposition
      of t-butylhydroperoxide was significantly enhanced by laccase. It can be assumed
      that the enzymatically generated phenoxy radicals mediate the production of
      oxygen centered radicals (alkoxy or peroxy) which initiate grafting.

PMID- 11240207
TI  - Production of pectinases by Polyporus squamosus in aqueous two-phase system.
AB  - The ability of Polyporus squamosus to grow and produce pectinases in an aqueous
      two-phase medium composed of polyethylene glycol and crude dextran is reported.
      Fungal growth was restricted to the bottom phase leaving the top phase cell free.
      Amounts of produced biomass and endo and exo-pectinase activities were superior
      or equal to those obtained in homogeneous medium. The partition coefficient for
      the endo-pectinase was 1.52 followed by a top phase yield of 70.86%. Although the
      phase system composition favours partition of a greater part of exo-pectinase
      activity to the bottom phase (K(exo) was 0.6 and yield in top phase 48.56%) the
      partitioned activity in the top phase was equal to that produced in homogeneous
      cultivation.

PMID- 11240208
TI  - Comparison of hydrolytic activity in water and heptane for thirty-two commercial
      lipase preparations.
AB  - The protein content and the rates of hydrolysis of p-nitrophenyl palmitate (pNPP)
      in water (soluble enzyme and emulsified substrate) and in heptane (soluble
      substrate and insoluble enzyme) were measured for thirty-two commercial lipase
      preparations. The protein content of the powders varied in a wide range as well
      as the activity on emulsified pNPP showing the high heterogeneity of the
      commercial samples. Activity in heptane also varied but to a lesser extent than
      that in water. There was no direct correlation between activities in water and in
      heptane as assayed with the same hydrolytic reaction. The ratio of activity in
      heptane to that in water, R(O/A) ratio, was introduced to characterize activity
      in organic media. Six lipases showed R(O/A) values higher than 1 demonstrating a
      higher activity in organic solvent than in water. A linear correlation of R(O/A)
      with activity in water (log plot) suggested the strong influence of diffusional
      limitations on activity of solid enzyme suspended in organic solvents.

PMID- 11240209
TI  - The role of macrophages in immune-mediated damage to the peripheral nervous
      system.
AB  - Macrophage-mediated segmental demyelination is the pathological hallmark of
      autoimmune demyelinating polyneuropathies, including the demyelinating form of
      Guillain-Barre syndrome and chronic inflammatory demyelinating polyneuropathy.
      Macrophages serve a multitude of functions throughout the entire pathogenetic
      process of autoimmune neuropathy. Resident endoneurial macrophages are likely to
      act as local antigen-presenting cells by their capability to express major
      histocompatibility complex antigens and costimulatory B7-molecules, and may thus
      be critical in triggering the autoimmune process. Hematogenous infiltrating
      macrophages then find their way into the peripheral nerve together with T-cells
      by the concerted action of adhesion molecules, matrix metalloproteases and
      chemotactic signals. Within the nerve, macrophages regulate inflammation by
      secreting several pro-inflammatory cytokines including IL-1, IL-6, IL-12 and TNF
      alpha. Autoantibodies are likely to guide macrophages towards their myelin or
      primarily axonal targets, which then attack in a complement-dependent and
      receptor-mediated manner. In addition, non-specific tissue damage occurs through
      the secretion of toxic mediators and cytokines. Later, macrophages contribute to
      the termination of inflammation by promoting T-cell apoptosis and expressing anti
      inflammatory cytokines including TGF-beta1 and IL-10. During recovery, they are
      tightly involved in allowing Schwann cell proliferation, remyelination and axonal
      regeneration to proceed. Macrophages, thus, play dual roles in autoimmune
      neuropathy, being detrimental in attacking nervous tissue but also salutary, when
      aiding in the termination of the inflammatory process and the promotion of
      recovery.

PMID- 11240210
TI  - The subiculum: a review of form, physiology and function.
AB  - We review the neuroanatomical, neurophysiological and functional properties of
      the mammalian subiculum in this paper. The subiculum is a pivotal structure
      positioned between the hippocampus proper and entorhinal and other cortices, as
      well as a range of subcortical structures. It is an under-investigated region
      that plays a key role in the mediation of hippocampal-cortical interaction. We
      argue that on neuroanatomical, physiological and functional grounds, the
      subiculum is properly part of the hippocampal formation, given its pivotal role
      in the hippocampal circuit. We suggest that the term "subicular complex" embraces
      a heterogenous range of distinct structures and this phrase does not connote a
      functionally or anatomically meaningful grouping of structures. The subiculum has
      a range of electrophysiological and functional properties which are quite
      distinct from its input areas; given the widespread set of cortical and
      subcortical areas with which it interacts, it is able to influence activity in
      quite disparate brain regions. The rules which govern the plasticity of synaptic
      transmission are not well-specified; it shares some properties in common with the
      hippocampus proper, but behaves quite differently in other respects. Equally, its
      functional properties are not well-understood, it plays an important but ill
      defined role both in spatial navigation and in mnemonic processing. The important
      challenges for the future revolve around the theoretical specification of its
      unique contribution to hippocampal formation processing on the one hand, and the
      experimental investigation of the many open questions (anatomical, physiological,
      pharmacological, functional) regarding its properties, on the other.

PMID- 11240211
TI  - Ammonium in nervous tissue: transport across cell membranes, fluxes from neurons
      to glial cells, and role in signalling.
AB  - Most, but not all, animal cell membranes are permeable to NH3, the neutral,
      minority form of ammonium which is in equilibrium with the charged majority form
      NH4+. NH4+ crosses many cell membranes via ion channels or on membrane
      transporters, and cultured mammalian astrocytes and glial cells of bee retina
      take up NH4+ avidly, in the latter case on a Cl(-)-cotransporter selective for
      NH4+ over K+. In bee retina, a flux of ammonium from neurons to glial cells is an
      essential component of energy metabolism, which involves a flux of alanine from
      glial cells to neurons. In mammalian brain, both glutamate and ammonium are taken
      up preferentially by astrocytes and form glutamine. Glutamine is transferred to
      neurons where it is deamidated to re-form glutamate; the maintenance of this
      cycle appears to require a substantial flux of ammonium from neurons to
      astrocytes. In addition to maintaining the glial cell content of fixed N (a
      "bookkeeping" function), ammonium is expected to participate in the regulation of
      glial cell metabolism (a signalling function): it will increase conversion of
      glutamate to glutamine, and, by activating phosphofructokinase and inhibiting the
      alpha-ketoglutarate dehydrogenase complex, it will tend to increase the formation
      of lactate.

PMID- 11240212
TI  - Kynurenines in the CNS: from endogenous obscurity to therapeutic importance.
AB  - In just under 20 years the kynurenine family of compounds has developed from a
      group of obscure metabolites of the essential amino acid tryptophan into a source
      of intensive research, with postulated roles for quinolinic acid in
      neurodegenerative disorders, most especially the AIDS-dementia complex and
      Huntington's disease. One of the kynurenines, kynurenic acid, has become a
      standard tool for use in the identification of glutamate-releasing synapses, and
      has been used as the parent for several groups of compounds now being developed
      as drugs for the treatment of epilepsy and stroke. The kynurenines represent a
      major success in translating a basic discovery into a source of clinical
      understanding and therapeutic application, with around 3000 papers published on
      quinolinic acid or kynurenic acid since the discovery of their effects in 1981
      and 1982. This review concentrates on some of the recent work most directly
      relevant to the understanding and applications of kynurenines in medicine.

PMID- 11240213
TI  - A critical review of the psychophysiology of driver fatigue.
AB  - Driver fatigue is a major cause of road accidents and has implications for road
      safety. This review discusses the concepts of fatigue and provides a summary on
      psychophysiological associations with driver fatigue. A variety of
      psychophysiological parameters have been used in previous research as indicators
      of fatigue, with electroencephalography perhaps being the most promising. Most
      research found changes in theta and delta activity to be strongly linked to
      transition to fatigue. Therefore, monitoring electroencephalography during driver
      fatigue may be a promising variable for use in fatigue countermeasure devices.
      The review also identified anxiety and mood states as factors that may possibly
      affect driver fatigue. Furthermore, personality and temperament may also
      influence fatigue. Given the above, understanding the psychology of fatigue may
      lead to better fatigue management. The findings from this review are discussed in
      the light of directions for future studies and for the development of fatigue
      countermeasures.

PMID- 11240214
TI  - Sensory gating of auditory evoked potentials in rats: effects of repetitive
      stimulation and the interstimulus interval.
AB  - In the P50 gating or conditioning-testing (C-T) paradigm, the P50 response, a
      small positive midlatency ( approximately 50 ms after stimulus onset) component
      of the human auditory evoked potential (AEP), is reduced towards the second click
      (S2) as compared to the response to the first click (S1). This phenomenon is
      called sensory gating. The putative function of sensory gating is thought to
      protect subjects from being flooded by irrelevant stimuli. Comparative studies
      have been done in rats in order to elucidate the underlying neural substrate of
      sensory gating. However, for a direct comparison of rat and human AEP components,
      it is imperative for both components to show similar characteristics. The amount
      of sensory gating in humans is dependent on repetitive stimulation and the
      interstimulus interval (ISI). In the present study effects of repetitive
      stimulation (Experiment 1) and various ISIs (Experiment 2) were determined on rat
      AEP components. The results demonstrate that gating is not limited to a
      restricted cortical area or a single midlatency component and that repetitive
      stimulation and ISI affect gating of several rat AEP components. Components such
      as the vertex P17 and N22 show a decrease in gating within several S1-S2
      presentations, mainly due to a decrease in amplitude to S1 (Experiment 1). Gating
      for vertex components (such as the P17, N22 and N50) is ISI dependent (Experiment
      2), but there is no interval in the 200-600 ms range at which optimal gating
      occurs. The ISI effects on gating are due to an increase of the amplitude to S2.
      The results have implications for the discussion about the rat homologue of the
      human P50.

PMID- 11240215
TI  - Does smelling granny relieve depressive mood? Commentary on "Rapid mood change
      and human odors".
AB  - Chen and Haviland-Jones claim if you're down/You needn't be depressed and mope
      around/Check out Granny's smell/It'll make you feel well/One problem: no
      supporting evidence was found.

PMID- 11240217
TI  - Exhaustive additivity suggests a new stage not an alternative model: A commentary
      on Fowler, Hofer and Lipitkas (2000).
AB  - Fowler et al. (Fowler, B., Hofer, K., Lipitkas, J., 2000. The exhaustive
      additivity displayed by nitrous oxide has implications for cognitive-energetical
      theory. Biol. Psychol. 52, 161-180) observed that nitrous oxide (N(2)O, an
      inhalation anaesthetic) does not interact with experimental manipulations derived
      from the additive factors literature. They proposed a two-tiered cognitive
      energetical model to account for the apparent "exhaustive additivity". This model
      assumes that N(2)O affects a lower tier resulting in a non-selective effect on an
      upper tier, which is comprised of energetical mechanisms that are selectively
      linked to processing stages. In this commentary, it is argued that the
      "exhaustive additivity" can easily be accomodated by linear stage models. The
      findings of Fowler et al. suggest a new stage rather than a new model. Moreover,
      their new model seems to predict "exhaustive interaction" rather than "exhaustive
      additivity". It is concluded that Fowler et al. may have a highly interesting
      finding, but not for the reasons they submitted when accounting for the
      "exhaustive additivity" displayed by N(2)O.

PMID- 11240220
TI  - Miniature data loggers for remote measurement of body temperature in medium-sized
      rodents.
AB  - We have investigated the use of miniature temperature data loggers for the
      recording of abdominal temperature in laboratory animals, using the guinea pig as
      a model. The data loggers, which are small (16cm(3)), light (20g) and have a
      battery life of +/-5 years, recorded both the normal abdominal temperature of
      guinea pigs, and their febrile response to an intramuscular injection of 50ug/kg
      lipopolysaccharide (E. coli) every 5min for the duration of the experiment (21
      days), to a resolution of at least 0.05 degrees C. No calibration shifts or loss
      of data occurred during the study period. However, despite their small size and
      versatility, we found that the loggers were suited for use only in guinea pigs
      with a body mass of approximately 600g or greater. In smaller animals, the
      loggers caused peritonitis.

PMID- 11240221
TI  - Thermal sensitivity of growth, food intake and activity of juvenile brown trout.
AB  - Growth rate, food intake and activity of juvenile brown trout (Salmo trutta L.)
      were studied at 10 constant temperatures (2.6-22.3 degrees C) and using eight
      full-sib families. We found between-family differences in growth rate but not
      significant temperaturexfamily interaction. The effects of temperature were well
      described by polynomial regressions that allowed the calculation of optima,
      performance breadths and thermal limits. The obtained values were noticeably
      higher and the performance breadth wider, than previously reported data for the
      species.

PMID- 11240222
TI  - Effects of adrenergic blockade on the daily rhythms of body temperature and
      oxygen consumption of the black-tailed tree rat (Thallomys nigricauda) maintained
      under different photoperiods.
AB  - (1) Measurements of VO(2) and T(b) daily rhythms in T. nigricauda were conducted.
      (2) Three different effects on VO(2) and T(b) were assessed: alpha and beta
      blockade, time of the day, and photoperiod regime. (3) Results show that in T.
      nigricauda, the response of T(b) and VO(2) differs significantly under the
      different photoperiod regimes. Rats acclimated to 16L:8D increased T(b) values as
      a response to beta blockade, while alpha blockade caused a decrease in T(b). (4)
      VO(2) values of T. nigricauda acclimated to 11.5L:12.5D responded differently to
      alpha and beta blockade. It can be assumed that the thermoregulatory responses
      with beta blockade are through a decrease in heat production, rather than through
      heat dissipation. However, in the case of alpha blockade, it may be assumed that
      heat dissipation, through vasodilation, is the cause for the decrease in T(b)
      values.

PMID- 11240223
TI  - Comparison of erythrocyte osmotic fragility among ectotherms and endotherms at
      three temperatures.
AB  - 1. Comparison of erythrocyte osmotic fragility (EOF) between various ectotherms
      and endotherms was investigated at 5, 25, and 38 degrees C. 2. We hypothesized
      that ectotherms might possess erythrocytes whose osmotic fragility would be less
      affected by temperature than those of endotherms. 3. Ectotherm erythrocytes were
      much more osmotically resistant than those of endotherms. 4. The EOF of
      ectotherms and endotherms showed similar responses to temperature. 5. It does not
      appear that the osmotic fragility of erythrocytes from ectotherms in this study
      are adapted to be less affected by temperature than those of endotherms. The
      highly osmotic resistant erythrocytes of ectotherms may alleviate the need for
      further adaptation for osmotic resistance.

PMID- 11240224
TI  - Oxygen isotope variability in bones of wild caught and constant temperature
      reared sub-adult American alligators.
AB  - (1) The mean delta18O(BP) ( per thousandSMOW) for any given bone sampled from
      captive alligators maintained at high constant temperature was lower (indicative
      of higher temperatures of bone deposition) than that of the same bone from wild
      alligators caught in Northern Florida, but these differences were only greater
      than two standard deviations from the mean for the thoracic vertebrae and
      metatarsal bones. (2) Inter-bone variability of delta18O(BP) ( per thousandSMOW)
      was similar for captive alligators maintained at constant temperatures and the
      wild alligators, but intra-bone variability was much greater in wild alligators.
      (3) The order of mean delta18O(BP) ( per thousandSMOW) of bones (from highest to
      lowest) differed between treatment groups. However, intra-bone variability
      obscured the significance of those differences. Nevertheless, the thoracic
      vertebra had the highest mean delta18O(BP) ( per thousandSMOW), indicative of
      lower temperatures, and the lowest variability of bones in both groups of
      alligators. Conversely, the tibia was one of the warmest and more variable bones
      in both groups of alligators. (4) The pattern of delta18O(BP) ( per thousandSMOW)
      values across sites within long bones were identical between alligator treatment
      groups for the femur and humerus but differed between groups for the tibia and
      metatarsus, and differed between different long bones. The predicted intra-bone
      pattern for long bones of increasing delta18O(BP) ( per thousandSMOW) indicative
      of lower temperatures in more distal sampling sites was only obtained from the
      femurs. (5) Paired cortical and cancellous bone samples from the same site from
      all individuals in both treatment groups were available for proximal humeri and
      distal femurs. delta18O(BP) ( per thousandSMOW) values from cortical bone were
      more variable than those from cancellous bone for both bones. (6) Cortical bone
      had lower delta18O(BP) ( per thousandSMOW) values indicative of warmer
      temperatures than cancellous bone at sites sampled on the proximal humeri and
      distal femurs of all three animals from both treatment groups.

PMID- 11240225
TI  - How much energy do barn owls (Tyto alba) save by roosting?
AB  - (1) The energy savings associated with the roosting behaviour of barn owls (Tyto
      alba) were determined with a biophysical model using measurements of microclimate
      from a roost and nest site in SW Scotland (55 degrees 10' N 3 degrees 12' W) from
      April 1991-March 1992. (2) The roost building provided complete shelter from wind
      and precipitation. Air temperature inside the roost building was 1.4 degrees C
      greater than ambient and matched the seasonal change in temperature. Air
      temperature inside the nest box was on average only 0.8 degrees C greater than
      ambient but was 2-3 degrees C warmer when adults and chicks were in the nest
      during the breeding season. (3) Estimated metabolic heat production was
      significantly different between locations and averaged 67.9, 68.1, 75.5 and
      84.2Wm(-2) for a barn owl roosting in the building, nest box, spruce tree and in
      the open, respectively. At night metabolic heat production was greater by 4-12%
      compared with daytime, depending on location. (4) Heat loss was 30% greater in
      winter months than in the summer in all locations. By roosting in the building an
      owl would make savings of 21.6Wm(-2) in March but only 12.9Wm(-2) in August. In a
      tree roost a barn owl would save 11.8Wm(-2) in March and 5.8Wm(-2) in August. (5)
      Barn owls were estimated to reduce metabolic heat production by 19% by roosting
      in the building and by 10% by roosting in a tree. In the building and tree
      savings of 21 and 9% occurred during the day compared with 17 and 12% at night.
      (6) Metabolic savings were strongly dependent on weather conditions with average
      metabolic savings of 26% occurring in wet and windy conditions compared with only
      12% on dry-calm days. Maximum savings of 29-36% occurred on wet days. (7) Barn
      owls appear to compensate for high metabolic demands for heat production by
      taking advantage of better thermal conditions within buildings, especially during
      the day when metabolic savings are greatest.

PMID- 11240226
TI  - Feeding causes thermophily in the woodhouse's toad (Bufo woodhousii).
AB  - (1) We placed 12 toads (Bufo woodhousii) in linear thermal gradients with floor
      temperatures ranging from 10 to 40 degrees C and monitored body temperatures
      (T(b)'s) with chromega-alomega thermocouples interfaced with a datalogger. (2) We
      measured T(b)'s at 10min intervals over a 24h period in toads that had eaten an
      equivalent of 5% of their body mass or had fasted for 5 days. (3) The mean 24h
      T(b) did not differ significantly between the fed and fasted groups. (4) Hourly
      mean T(b)'s of fed toads differed significantly over the 24h, but those of fasted
      toads did not. Fed toads selected highest T(b)'s during late afternoon and
      evening.

PMID- 11240227
TI  - The search for proteins with immunochemical affinity to plant stress proteins at
      cold-adapted endemic Baikal fishes.
AB  - The search for proteins with immunochemical affinity to plant stress proteins in
      endemic Baikal fishes shows the presence of proteins, immunochemically related to
      plant heat-stabile proteins and plant uncoupling protein CSP 310. Western
      blotting showed that among the native cytoplasmic proteins of endemic Baikal
      fishes there are proteins immunochemically related to heat-stabile plant proteins
      with molecular weights about 480, 200-290, 150, 140 and about 90-100kD. SDS
      electrophoresis showed the presence of polypeptides with molecular weights 23, 17
      and 14kD in all species investigated and an additional 35kD polypeptide in
      Cottocomephorus grewingki. The search for polypeptides with immunochemical
      affinity to plant stress uncoupling protein CSP 310 in endemic Baikal fishes
      shows the presence of a 14kD polypeptide, immunochemically related to it.

PMID- 11240228
TI  - The effect of cold stress on ganglioside fatty acid composition and ganglioside
      bound sialic acid content of rat brain subcellular fractions.
AB  - The effect of cold stress on the ganglioside fatty acid composition and sialic
      acid content of brain subcellular fractions and homogenate of rats was studied,
      the animals were kept in a cold room with 12h light-dark cycles at 3 and 10
      degrees C for 2 weeks. (1) The rat brain homogenate, synaptosomes and myelin of
      rats exposed to 3 degrees C contained significantly higher amounts of ganglioside
      bound sialic acid per mg of protein than these fractions of control rats kept at
      23 degrees C; the differences were less pronounced in rats exposed to 10 degrees
      C. (2) A small, but significant, diminution of relative palmitic acid content and
      an increase of stearic acid content was found to take place in gangliosides from
      rat brain synaptosomes, synaptosomal plasma membranes and homogenate as a result
      of the exposure of animals to 3 degrees C and to a lesser extent to 10 degrees C.
      (3) The content of unsaturated fatty acids in gangliosides from brain subcellular
      fractions was approximately the same in cold exposed and control rats.

PMID- 11240229
TI  - Genetic selection of rats with high and low body temperatures.
AB  - Body (core) temperature (T(c)) directly affects all biological processes,
      including sensitivity to toxic chemicals, development, aging, and drug
      metabolism. To understand how T(c) affects these processes it is necessary to
      alter T(c) independently of other physiological processes. The purpose of this
      study was to determine whether selective breeding techniques can be used to
      develop lines of rats with hyperthermic and hypothermic T(c)'s. T(c) and motor
      activity of 24 female and 23 male rats (parental line) of the NIH heterogenous
      stock were monitored by telemetry for 96h at a T(a) of 22 degrees C. The mean 24h
      T(c) of the male and female rats was 37.3 degrees C with a range of 37-38.2
      degrees C. T(c) was not correlated with motor activity or body weight. Pairs with
      the lowest and highest T(c)'s were selected for breeding. The F1 generation
      consisted of 10 offspring from the hyperthermic group and 20 from the hypothermic
      group. They were implanted with transmitters at 60d of age. T(c) of rats derived
      from the hyperthermic parental line had a significantly warmer T(c) than the rats
      derived from the hypothermic parental line. Motor activity was significantly
      higher in the hyperthermic F1 males and hypothermic F1 females. Breeding of
      hyperthermic and hypothermic rats has shown that adult offspring of the fourth
      generation maintain significantly different core temperatures but have similar
      patterns of motor activity. The results demonstrate that T(c) is heritable and
      that it should be feasible to develop lines of rats that regulate T(c) above or
      below normal.

PMID- 11240230
TI  - Thermal time constant estimation in warming and cooling ectotherms.
AB  - (1) Measurement of physiological control of warming and cooling in reptiles
      requires calculating the thermal time constant (tau) of the animal. (2)
      Previously reported methods of estimating tau are sensitive to multiple problems
      including measurement error in operative environmental temperature and
      equilibrium body temperature, drift of environmental temperatures, requirements
      for extremely simple thermal environments, and ill conditioning of the estimation
      techniques themselves. (3) We propose a physiologically based heat transfer model
      which is less sensitive to common experimental errors, more numerically robust,
      and can provide physiologically meaningful estimates of time constants. (4) The
      method presented here allows time constants to be measured for animals subjected
      to the traditional step change experiment as well as to shorter periods of
      warming and cooling such as during shuttling.

PMID- 11240231
TI  - A prospective study of salivary function sparing in patients with head-and-neck
      cancers receiving intensity-modulated or three-dimensional radiation therapy:
      initial results.
AB  - OBJECTIVES: In a prospective clinical study, we tested the hypothesis that
      sparing the parotid glands may result in significant objective and subjective
      improvement of xerostomia in patients with head-and-neck cancers. The functional
      outcome 6 months after the completion of radiation therapy is presented. METHODS
      AND MATERIALS: From February 1997 to February 1999, 41 patients with head-and
      neck cancers were enrolled in a prospective salivary function study. Inverse
      planning intensity-modulated radiation therapy (IMRT) was used to treat 27
      patients, and forward-planning three-dimensional radiation therapy in 14. To
      avoid potential bias in data interpretation, only patients whose submandibular
      glands received greater than 50 Gy were eligible. Attempts were made to spare the
      superficial lobe of the parotid glands to avoid underdosing tumor targets in the
      parapharyngeal space; however, the entire parotid volume was used to compute dose
      volume histograms (DVHs) for this analysis. DVHs were computed for each gland
      separately. Parotid function was assessed objectively by measuring stimulated and
      unstimulated saliva flow before and 6 months after the completion of radiation
      therapy. Measurements were converted to flow rate (mL/min) and normalized
      relative to that before treatment. The corresponding quality-of-life (QOL)
      outcome was assessed by five questions regarding the patient's oral discomfort
      and eating/speaking problems. RESULTS: We observed a correlation between parotid
      mean dose and the fractional reduction of stimulated saliva output at 6 months
      after the completion of radiation therapy. We further examined whether the
      functional outcome could be modeled as a function of dose. Two models were found
      to describe the dose-response data well. The first model assumed that each
      parotid gland is comprised of multiple independent parallel functional subunits
      (corresponding to computed tomography voxels) and that each gland contributes
      equally to overall flow, and that saliva output decreases exponentially as a
      quadratic function of irradiation dose to each voxel. The second approach uses
      the equivalent uniform dose (EUD) metrics, which assumes loss of salivary
      function with increase in EUD for each parotid gland independently. The analysis
      suggested that the mean dose to each parotid gland is a reasonable indicator for
      the functional outcome of each gland. The corresponding exponential coefficient
      was 0.0428/Gy (95% confidence interval: 0.01, 0.09). The QOL questions on
      eating/speaking function were significantly correlated with stimulated and
      unstimulated saliva flow at 6 months. In a multivariate analysis, a toxicity
      score derived from the model based on radiation dose to the parotid gland was
      found to be the sole significant predictive factor for xerostomia. Neither
      radiation technique (IMRT vs. non-IMRT) nor chemotherapy (yes or no)
      independently influenced the functional outcome of the salivary glands.
      CONCLUSION: Sparing of the parotid glands translates into objective and
      subjective improvement of both xerostomia and QOL scores in patients with head
      and-neck cancers receiving radiation therapy. Modeling results suggest an
      exponential relationship between saliva flow reduction and mean parotid dose for
      each gland. We found that the stimulated saliva flow at 6 months after treatment
      is reduced exponentially, for each gland independently, at a rate of
      approximately 4% per Gy of mean parotid dose.

PMID- 11240232
TI  - Prophylaxis of oral mucositis in irradiated head-and-neck cancer patients: a
      proposed classification scheme of interventions and meta-analysis of randomized
      controlled trials.
AB  - PURPOSE: To identify, classify, and evaluate agents used in the prophylaxis of
      oral mucositis in irradiated head and neck cancer patients. METHODS: Data sources
      included multiple databases and manual citation review of relevant literature.
      Based on the eligibility criteria, 59 studies were independently reviewed by two
      reviewers. Forty-two studies were included in the classification scheme, of which
      15 met the criteria for inclusion in the meta-analysis. Data were extracted by
      duplicate independent review, with disagreement resolved by consensus. RESULTS:
      Overall, the interventions reduced the odds of developing severe oral mucositis,
      when assessed by clinicians, by 36% (OR: 0.64; 95% CI: 0.46, 0.88). Subgroup
      analysis suggested that only the narrow-spectrum antibacterial lozenges were
      effective (OR: 0.45; 95% CI: 0.23, 0.86); however, the power of the aggregated
      data in the other classes may have been insufficient to detect differences. When
      the outcome was assessed by patients, no significant difference was seen in the
      outcome between the treatment and the control groups (OR: 0.79; 95% CI: 0.56
      1.12). CONCLUSIONS: Overall, interventions chosen on a sound biologic basis to
      prevent severe oral mucositis are effective. In particular, when oral mucositis
      is assessed by clinicians, narrow-spectrum antibiotic lozenges appear to be
      beneficial. Methodologic limitations were evident in many of the studies. Further
      research using validated measurement tools in larger, methodologically sound
      trials is warranted.

PMID- 11240233
TI  - Influence of age on the results of brachytherapy for early tongue cancer.
AB  - PURPOSE: To determine the influence of elder age on the results of brachytherapy
      for early (T1-2 N0 M0) oral tongue cancer and examine the compatibility of low
      dose rate (LDR) with high-dose rate (HDR) brachytherapy. METHODS AND MATERIALS:
      We analyzed 591 patients treated at Osaka University Hospital between 1967 and
      1999. We compared the results of radiotherapy for 156 elderly patients (137 LDR
      and 19 HDR) 65 years of age or older and 435 patients (383 LDR and 52 HDR) less
      than 65 years of age. RESULTS: HDR brachytherapy showed the same local control
      rate as LDR brachytherapy (81% at 3 years). Elderly patients showed a poorer
      local control rate (75% at 3 years) than the younger group (83% at 3 years)(p =
      0.002). Multivariate analysis identified age as the only prognostic factor for
      local control (p = 0.002). CONCLUSIONS: HDR brachytherapy achieved the same
      result as LDR brachytherapy. However, the elderly patient showed a higher rate of
      local recurrence after brachytherapy.

PMID- 11240234
TI  - Updated results of the phase III Radiation Therapy Oncology Group (RTOG) trial 85
      31 evaluating the potential benefit of androgen suppression following standard
      radiation therapy for unfavorable prognosis carcinoma of the prostate.
AB  - PURPOSE: To determine the potential advantage of androgen ablation following
      standard external-beam radiation therapy in patients with locally advanced
      (clinical or pathologic T3; clinical or pathologic node positive) carcinoma of
      the prostate. METHODS AND MATERIALS: In 1987 the RTOG initiated a Phase III trial
      of long-term adjuvant goserelin in definitively irradiated patients with
      carcinoma of the prostate. A total of 977 patients were accrued to the study of
      which 945 remain analyzable: 477 on the adjuvant hormone arm (Arm I); and 468 on
      the radiation only arm (Arm II) with hormones initiated at relapse. The initial
      results were reported in the Journal of Clinical Oncology in 1997. RESULTS: With
      a median follow up of 5.6 years for all patients and 6.0 years for living
      patients local failure at 8 years was 23% for Arm I and 37% for Arm II (p <
      0.0001). Distant metastasis was likewise favorably impacted with the immediate
      use of hormonal manipulation with a distant metastasis rate in Arm I of 27% and
      37% in Arm II (p < 0.0001). Disease-free survival (NED survival) and NED survival
      with PSA of 1.5 ng/mL (bNED) or less were both statistically significant in favor
      of the immediate hormone arm (both p < 0.0001). Cause-specific failure was not
      statistically different with a cause-specific failure of 16% for Arm I and 21% in
      Arm II (p = 0.23). Overall survival was likewise not statistically different
      between two arms, with a 49% overall survival at 8 years in Arm I and 47% in Arm
      II (p = 0.36). Subset analysis of centrally reviewed Gleason 8-10 patients who
      did not undergo prostatectomy showed that for patients receiving radiation
      therapy plus adjuvant hormones there was a statistically significant improvement
      in both absolute (p = 0.036) and cause-specific survival (p = 0.019).
      CONCLUSIONS: Use of long-term adjuvant androgen deprivation in addition to
      definitive radiation therapy results in a highly significant improvement in
      regards to local control, freedom from distant metastasis, and biochemical free
      survival in unfavorable prognosis patients with carcinoma of the prostate.

PMID- 11240235
TI  - Subset analysis of RTOG 85-31 and 86-10 indicates an advantage for long-term vs.
      short-term adjuvant hormones for patients with locally advanced nonmetastatic
      prostate cancer treated with radiation therapy.
AB  - PURPOSE: The benefit of adjuvant hormones in prostate cancer patients receiving
      definitive radiation therapy (RT) in RTOG 85-31 and 86-10 has previously been
      reported. This analysis excludes those patients with positive lymph nodes or
      postprostatectomy to determine the benefit of adjuvant hormones in men with
      locally advanced nonmetastatic prostate cancer receiving definitive RT. METHODS
      AND MATERIALS: Nine hundred ninety-three eligible patients from RTOG 85-31 and 86
      10 treated between 1987-1992 were included in this study. Five hundred seventy
      five patients with T3N0M0 disease were included from RTOG 85-31 and 418 patients
      with T2b-T4N0M0 disease from RTOG 86-10. Patients randomized to receive long-term
      hormones (LTH) on 85-31 received goserelin starting the last week of RT and
      continued indefinitely. Patients treated with short-term hormones (STH) on 86-10
      received goserelin and flutamide 2 months prior to and during RT. The median
      follow-up for all patients in this analysis was 71 months (range, 0.6-129
      months). RESULTS: Combining both studies, statistically significant improvements
      in outcome were observed between the RT and hormones (I) and RT alone (II) groups
      for biochemical disease-free survival (bNED control) and distant metastases
      failure (DMF). Statistically significant improvements in bNED control, DMF and
      cause-specific failure (CSF) were observed for patients receiving LTH compared
      with STH. In those patients receiving LTH, the benefit in bNED control (p =
      0.0002), DMF (p = 0.05), and CSF (p = 0.02) was limited to centrally reviewed
      Gleason score of 7 and 8-10 tumors. For all patients treated on 85-31,
      statistically significant improvements for bNED control, DMF, and CSF were
      observed between Group I and II. Multivariate analysis demonstrated Gleason score
      and the use of LTH to be independent predictors for bNED control (p < 0.0001),
      DMF (p < 0.0001), and CSF (p < 0.002). CONCLUSIONS: Based on this analysis,
      adjuvant long-term hormones compared to short-term hormones resulted in
      statistically significant improvements in bNED control, DMF, and CSF rates for
      patients with locally advanced nonmetastatic prostate cancer.

PMID- 11240236
TI  - The impact of irregularly rising prostate-specific antigen and "impending
      failure" on the apparent outcome of localized prostate cancer following
      radiotherapy.
AB  - PURPOSE: To examine the impact of irregularly rising prostate-specific antigen
      (PSA) and "impending" biochemical failure on the apparent rate of biochemical
      relapse following radiotherapy for localized prostate cancer. METHODS AND
      MATERIALS: We analyzed the outcome of 572 patients with T1/T2 prostate cancer
      treated with radiotherapy alone at the Princess Margaret Hospital (median follow
      up, 4.21 years). Biochemical outcomes were analyzed using 2 different definitions
      of failure: (1) the American Society for Therapeutic Radiology and Oncology
      (ASTRO) definition, and (2) a modified definition that included 2 consecutive
      rises in PSA, with a minimum rise of 1.5 ng/mL above the nadir, or a nadir value
      of greater than 4 ng/mL. Patients were defined as having "impending failure" when
      the last 2 PSA measurements taken demonstrated 2 consecutive rises. RESULTS: Two
      hundred and thirty patients (40%) met the ASTRO definition of failure; 258
      patients (48%) failed by the modified definition (p = 0.001). Five-year
      biochemical relapse-free rate (bNED) rate was 55% using the ASTRO definition, and
      49% using the modified definition. This difference in 5-year bNED was greatest
      for patients with high-risk disease (ASTRO definition 30% vs. modified definition
      15%). Twenty-four of the 38 additional cases identified as biochemical failures
      by the modified definition had irregularly rising PSA levels; 14 were "impending
      failures." These additional 38 patients had a median PSA elevation 5.4 ng/mL
      above the nadir, and a high risk of subsequent clinical failure (4-year clinical
      failure-free rate of 63%). The ASTRO definition had a sensitivity of 87% and
      specificity of 74% for predicting clinical relapse. The modified definition had a
      sensitivity of 95% and a specificity of 70%. CONCLUSION: A definition of
      biochemical failure that includes an absolute allowable rise in PSA above the
      nadir can identify patients with rising PSA who are at substantial risk of
      clinical relapse, but who are not defined as biochemical failures by the ASTRO
      definition. This is particularly true for patients with high-risk disease. The
      use of a uniform definition of biochemical failure is crucial to ensure that
      differences in apparent outcome are not due to differences in the definition of
      relapse. Currently, the ASTRO definition should remain the standard. Large cohort
      studies with long follow-up can be utilized to optimize the definition of
      biochemical failure following radiotherapy for prostate cancer.

PMID- 11240237
TI  - External irradiation and intraluminal irradiation using middle-dose-rate iridium
      in patients with roentgenographically occult lung cancer.
AB  - PURPOSE: Therapeutic results were analyzed in 39 patients with
      roentgenographically occult lung cancer (ROLC), and the significance and optimal
      dose of this therapy were evaluated. METHODS AND MATERIALS: The subjects were 39
      patients who underwent intraluminal irradiation between May 1987 and August 1999.
      Radiotherapy was performed by combining external irradiation with intraluminal
      irradiation using middle-dose-rate iridium (four 370-MBq wires) through a
      catheter with a spacer, which held the source in the center of the bronchus. The
      doses of radiation were 22-66 Gy (median value 45 Gy) by external irradiation and
      10-46 Gy (median value 28 Gy) by intraluminal irradiation. RESULTS: The
      therapeutic effect was CR in 38 patients and PR in 1, and local recurrence was
      observed in a PR case and 3 of the 38 patients who showed CR. The 3-year and 5
      year relapse-free survival rates were both 87%. No severe radiation injury was
      observed. CONCLUSIONS: Considering that ROLC often occurs as multiple cancers and
      that many patients with ROLC have reduced lung function, radiation therapy by a
      combination of intraluminal irradiation and external irradiation is expected to
      replace surgery as the first choice for the treatment of this disease in the
      twenty-first century.

PMID- 11240238
TI  - Estimating the need for radiotherapy for lung cancer: an evidence-based,
      epidemiologic approach.
AB  - BACKGROUND AND OBJECTIVES: Current estimates of the proportion of cancer patients
      who will require radiotherapy (RT) are based almost entirely on expert opinion.
      The objective of this study was to use an evidence-based approach to estimate the
      proportion of incident cases of lung cancer that will require RT at any point in
      the evolution of the illness. METHODS: A systematic review of the literature was
      undertaken to identify indications for RT for lung cancer, and to ascertain the
      level of evidence that supported each indication. An epidemiologic approach was
      then used to estimate the incidence of each indication for RT in a typical North
      American population of lung cancer patients. The effect of sampling error on the
      estimated appropriate rate of RT was calculated mathematically, and the effect of
      systematic error, was estimated by sensitivity analysis. RESULTS: It was shown
      that 53.6% +/- 3.3% of small-cell lung cancer (SCLC) cases develop one or more
      indications for RT at some point in the course of the illness, 45.4% +/- 4.3% in
      their initial treatment, and 8.2% +/- 1.5% later for recurrence of progression.
      Overall, 64.3% +/- 4.7% of non-small-cell lung cancer (NSCLC) cases require RT,
      45.9% +/- 4.3% in their initial treatment, and 18.3% +/- 1.8% later in the course
      of the illness. The proportion of NSCLC cases that ever require RT is stage
      dependent; 41.0% +/- 5.5% in Stage I; 54.5% +/- 6.5% in Stage II; 83.5% +/- 10.6%
      in Stage III; and 65.7% +/- 7.6% in Stage IV. In total, 61.0% +/- 3.9% of all
      patients with lung cancer will develop one or more indications for RT at some
      point in the illness, 44.6% +/- 3.6% in their initial treatment, and 16.5% +/-
      1.5% later for recurrence or progression. CONCLUSION: This method provides a
      rational starting point for the long-term planning of radiation services, and for
      the audit of access to RT at the population level. We now plan to extend this
      study to the other major cancer sites to enable us to estimate the appropriate RT
      treatment rate for the cancer population as a whole.

PMID- 11240239
TI  - Preoperative combined modality therapy for clinically resectable uT3 rectal
      adenocarcinoma.
AB  - PURPOSE: To determine the acute toxicity, outcome, and sphincter preservation
      rates in patients with clinically resectable uT3 adenocarcinoma of the rectum
      treated with preoperative combined modality therapy. METHODS AND MATERIALS: A
      total of 72 patients were treated from 12/90-7/98 with preoperative 50.4 Gy plus
      2 cycles of concurrent 5-fluorouracil (5-FU) and leucovorin (LV) bolus daily x 5
      followed by sharp or total mesorectal excision and 4 cycles of postoperative 5-FU
      and LV. RESULTS: Individual Grade 3+ toxicities during preoperative therapy
      included diarrhea, 11%; bowel movements, 9%; leukopenia, 18%; tenesmus, 1%; and
      thrombocytopenia, 1%. Total Grade 3+ toxicity was 28%. The pathologic complete
      response (CR) rate was 13%, and an additional 9% had a clinical CR for a total CR
      rate of 22%. Of the 35 patients who were judged clinically by their operating
      surgeon to require an abdominoperineal resection (APR) and were therefore treated
      with the goal of sphincter preservation, 89% were able to undergo sphincter
      preserving surgery. Of the 21 patients eligible for analysis, 81% had good to
      excellent sphincter function. The 3-year actuarial patterns of failure were 2%
      local, 8% abdominal, and 13% distant. The 3-year actuarial survival was 95%.
      CONCLUSIONS: Our data confirm our preliminary reports of encouraging rates of
      acute toxicity, local control, survival, sphincter preservation and function with
      preoperative combined modality therapy. It is an alternative approach for the
      treatment of uT3 clinically resectable rectal cancer.

PMID- 11240240
TI  - Experience with split-course external beam irradiation +/- chemotherapy and
      integrated Ir-192 high-dose-rate brachytherapy in the treatment of primary
      carcinomas of the anal canal.
AB  - PURPOSE: The effect of the treatment of anal cancer by performing a high-dose
      rate (HDR) brachytherapy boost during a short split between the external beam
      radiotherapy series (EBR) +/- chemotherapy was investigated. METHODS AND
      MATERIALS: Thirty-nine patients with anal canal cancers, stages T1-T4 N0-2 M0,
      were treated with split-course EBR (50-50.4 Gy) and a Iridium 192 ((192)Ir-) HDR
      boost (6 Gy) performed during the 1-2-week split. Patients who failed to achieve
      a complete tumor response received additional brachytherapy. Chemotherapy with 5
      fluorouracil and mitomycin C was offered to patients with tumors > 3 cm and
      employed concomitantly on days 1-5 and day 1, respectively, of each EBR series.
      RESULTS: Follow-up ranged from 3 to 140 months (median 31). Median treatment
      duration was 56 days. The 3-year (5-year) actuarial rates of locoregional control
      (LRC) and disease-specific survival (DSS) were 81% (76%) and 80% (76%),
      respectively. The crude rate of anal preservation was 77% overall, and 97% in
      patients in whom LRC was achieved. Uncompromised anal function was recorded in
      93% of these patients. The actuarial 3-year (5-year) rate of colostomy-free
      survival (CFS) was 78% (73%). There was a statistically significant difference in
      LRC and DSS according to stage, tumor size, and nodal status. Complications
      requiring surgical intervention occurred in 7.6% of patients. CONCLUSION: The
      integration of the HDR boost in a split-course EBR regimen +/- chemotherapy
      resulted in excellent sphincter function without an increase of severe
      complications and with rates of LRC, DSS, and CFS, which compare favorably with
      those reported in the literature.

PMID- 11240241
TI  - Squamous cell carcinoma of the anal canal.
AB  - PURPOSE: To report the results of primary radiotherapy for treatment of anal
      canal carcinoma from the University of Florida series and review issues related
      to treatment of this disease. METHODS AND MATERIALS: Forty-nine patients were
      treated with primary radiation therapy (RT) for cure. Patients had a minimum 2
      year follow-up (median, 9.8 years). After 1990, patients with lesions of at least
      3 cm also received chemotherapy with fluorouracil (1000 mg/m(2)) plus cisplatin
      (100 mg/m(2)) or mitomycin (10-15 mg/m(2)) if medically fit (n = 26). RT was
      delivered with a 4-field box technique to deliver 45 Gy in 25 fractions. The
      inguinal nodes were treated daily using electrons to supplement the dose in that
      region to a total dose of 45 Gy if clinically negative or about 60 Gy if
      involved. There were no planned breaks. A 10- to 15-Gy boost was delivered using
      interstitial iridium 192 implant (n = 32), en face (60)Co field (n = 5), or
      external-beam photon fields (n = 11). RESULTS: Local control rates at 5 years
      were 100% for T1N0, 92% for T2N0 or N1, 75% for T3N0, 67% for T4N0, 88% for
      T4N(pos) or T(any)N2-3, and 85% overall. With surgical salvage, ultimate local
      control rates were 100%, 100%, 81%, 100%, and 88%, respectively, with 92%
      overall. Cause-specific survival rates at 5 years were 100% for Stage I, 88% for
      Stage II, 100% for Stage IIIA, and 70% for Stage IIIB. Absolute survival rates at
      5 years were 62%, 68%, 100%, and 70%. Sphincter preservation rates were 83%, 79%,
      75%, and 100% by stage and 81% overall. There was an improvement in local control
      with the addition of chemotherapy in more advanced disease, but it was not
      significant. There was an increase in acute toxicity with the addition of
      chemotherapy (12% > or = Grade 4) but not long-term toxicity. Late toxicity
      requiring colostomy occurred in 6% of patients and consisted of soft tissue
      necrosis. CONCLUSIONS: The majority of patients with anal canal carcinoma can be
      treated with curative intent using a sphincter-sparing approach of radiation with
      or without chemotherapy even with advanced disease. With the addition of
      chemotherapy to radiation, there is an increased risk of acute toxicity and about
      1-2% incidence of toxic death. Smaller tumors (T1 and early T2) probably do not
      require the addition of chemotherapy.

PMID- 11240242
TI  - Serum proinflammatory cytokine response in patients with advanced liver tumors
      following selective internal radiation therapy (SIRT) with (90)Yttrium
      microspheres.
AB  - PURPOSE: To determine the changes in serum levels of proinflammatory cytokines
      within 48 h after selective internal radiation treatment (SIRT) in patients with
      advanced liver cancers. METHODS AND MATERIALS: Twenty-eight patients with
      advanced liver cancers who underwent SIRT were recruited into the study. Serum
      levels of interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor
      alpha, and interferon-gamma were determined prior to and 3, 6, 12, 24, and 48 h
      after SIRT. Their changes were correlated to adverse reactions following
      treatment as assessed by constitutional symptom scores, and routine blood and
      liver function tests at 24 and 48 h post-SIRT and falls in serum carcinoembryonic
      antigen (CEA) level 1 month post-SIRT. RESULTS: Serum IL-6 levels were
      significantly increased at 24 (p < or = 0.05) and 48 h (p < or = 0.01) post-SIRT.
      In contrast, there was no significant change in the serum levels of other
      cytokines studied. The increase in serum IL-6 at 24 h post-SIRT was significantly
      correlated with the changes in serum alanine transferase (p < or = 0.05) and C
      reactive protein (p < or = 0.001) levels and total leukocyte counts (p < or =
      0.001) at both 24 and 48 h post-SIRT. Changes in serum IL-6 level were also
      significantly correlated to the rise of serum aspartate transaminase levels at 48
      h post-SIRT (p < or = 0.001), but not with the scores of constitutional symptoms
      or the changes of serum CEA at 1 month post-SIRT. CONCLUSION: Absence of
      significant changes in most of proinflammatory cytokines studied confirmed that
      SIRT is a reasonably safe and well-tolerated treatment with minimal side-effect
      from the point of view of cytokine-related inflammation. The correlation of serum
      IL-6 changes with several liver enzymes and C-reactive protein but not with
      clinical symptom scores or serum CEA levels suggests that the rise in IL-6 levels
      in the first 48 h following SIRT most likely reflect normal liver cell damage
      rather than tumor cell damage.

PMID- 11240243
TI  - Cardiac perfusion changes in patients treated for breast cancer with radiation
      therapy and doxorubicin: preliminary results.
AB  - PURPOSE: To determine the incidence and dose dependence of regional cardiac
      perfusion abnormalities in patients with left-sided breast cancer treated with
      radiation therapy (RT) with and without doxorubicin (Dox). METHODS: Twenty
      patients with left-sided breast cancer underwent cardiac perfusion imaging using
      single photon emission computed tomography (SPECT) prechemotherapy, pre-RT, and 6
      months post-RT. SPECT perfusion images were registered onto 3-dimensional (3D) RT
      dose distributions. The volume of heart in the RT field was quantified, and the
      regional RT dose was calculated. A decrease in regional cardiac perfusion was
      assessed subjectively by visual inspection and objectively using image fusion
      software. Ten patients received Dox-based chemotherapy (total dose 120-300
      mg/m(2)), and 10 patients had no chemotherapy. RT was delivered by tangent beams
      in all patients to a total dose of 46-50 Gy. RESULTS: Overall, 60% of the
      patients had new visible perfusion defects 6 months post-RT. A dose-dependent
      perfusion defect was seen at 6 months with minimal defect appreciated at 0-10 Gy,
      and a 20% decrease in regional perfusion at 41-50 Gy. One of 20 patients had a
      decrease in left ventricle ejection fraction (LVEF) of greater than 10% at 6
      months; 2/20 patients had developed transient pericarditis. No instances of
      myocardial infarction or congestive heart failure (CHF) have occurred.
      CONCLUSIONS: RT causes cardiac perfusion defects 6 months post-RT in most
      patients. Long-term follow-up is needed to assess whether these perfusion changes
      are transient or permanent and to determine if these findings are associated with
      changes in overall cardiac function and clinical outcome.

PMID- 11240244
TI  - Hyperbaric oxygen therapy for late sequelae in women receiving radiation after
      breast-conserving surgery.
AB  - PURPOSE: Persisting symptomatology after breast-conserving surgery and radiation
      is frequently reported. In most cases, symptoms in the breast resolve without
      further treatment. In some instances, however, pain, erythema, and edema can
      persist for years and can impact the patient's quality of life. Hyperbaric oxygen
      therapy was shown to be effective as treatment for late radiation sequelae. The
      objective of this study was to assess the efficacy of hyperbaric oxygen therapy
      in symptomatic patients after breast cancer treatment. PATIENTS AND METHODS:
      Forty-four patients with persisting symptomatology after breast-conservation
      therapy were prospectively observed. Thirty-two women received hyperbaric oxygen
      therapy in a multiplace chamber for a median of 25 sessions (range, 7-60). One
      hundred percent oxygen was delivered at 240 kPa for 90-min sessions, 5 times per
      week. Twelve control patients received no further treatment. Changes throughout
      the irradiated breast tissue were scored prior to and after hyperbaric oxygen
      therapy using modified LENT-SOMA criteria. RESULTS: Hyperbaric oxygen therapy
      patients showed a significant reduction of pain, edema, and erythema scores as
      compared to untreated controls (p < 0.001). Fibrosis and telangiectasia, however,
      were not significantly affected by hyperbaric oxygen therapy. Seven of 32 women
      were free of symptoms after hyperbaric oxygen therapy, whereas all 12 patients in
      the control group had persisting complaints. CONCLUSIONS: Hyperbaric oxygen
      therapy should be considered as a treatment option for patients with persisting
      symptomatology following breast-conserving therapy.

PMID- 11240245
TI  - The American Brachytherapy Society recommendations for brachytherapy of soft
      tissue sarcomas.
AB  - PURPOSE: This report presents the American Brachytherapy Society (ABS) guidelines
      for the use of brachytherapy for patients with soft tissue sarcoma. METHODS AND
      MATERIALS: Members of the ABS with expertise in soft tissue sarcoma formulated
      brachytherapy guidelines based upon their clinical experience and a review of the
      literature. The Board of Directors of the ABS approved the final report. RESULTS:
      Brachytherapy used alone or in combination with external beam irradiation is an
      established means of safely providing adjuvant local treatment after resection
      for soft tissue sarcomas in adults and in children. Brachytherapy options include
      low dose rate techniques with iridium 192 or iodine 125, fractionated high dose
      rate brachytherapy, or intraoperative high dose rate therapy. Recommendations are
      made for patient selection, techniques, dose rates, and dosages. Complications
      and possible interventions to minimize their occurrence and severity are
      reviewed. CONCLUSION: Brachytherapy represents an effective means of enhancing
      the therapeutic ratio, offering both biologic and dosimetric advantage in the
      treatment of patients with soft tissue sarcoma. The treatment approach used
      depends upon the institution, physician expertise, and the clinical situation.
      Guidelines are established for the use of brachytherapy in the treatment of soft
      tissue sarcomas in adults and in children. Practitioners and cooperative groups
      are encouraged to use these guidelines to formulate their treatment and dose
      reporting policies. These guidelines will be modified, as further clinical
      results become available.

PMID- 11240246
TI  - Risk for hemorrhage during the 2-year latency period following gamma knife
      radiosurgery for arteriovenous malformations.
AB  - PURPOSE: Radiosurgery does not immediately obliterate an arteriovenous
      malformation (AVM), and the risk for hemorrhage still persists until the AVM is
      occluded. There is controversy about whether this risk is altered after as
      compared to before radiosurgery. The aim of this paper is to study this topic
      further and to suggest a model to predict the risk for posttreatment hemorrhage.
      METHODS AND MATERIALS: The incidence of hemorrhages within the first 24 months
      following Gamma Knife radiosurgery was studied retrospectively among 1593 AVM
      patients, and was related to patient, AVM, and treatment parameters. RESULTS:
      Fifty-six patients experienced a hemorrhage in the latency period, representing
      an average annual incidence of 1.8%. The incidence of posttreatment hemorrhage
      was related to the patient's age, AVM volume, minimum dose, and average dose
      delivered to the AVM nidus. Based on these observations, an equation was defined
      that could quantify the probability for a posttreatment hemorrhage to occur.
      CONCLUSION: A model that can predict the probability for a hemorrhage within the
      first 24 months after radiosurgery is presented. The risk is higher for larger
      AVMs and for older patients, and it is lower when higher doses of radiation are
      used.

PMID- 11240247
TI  - Proton radiation therapy for medium and large choroidal melanoma: preservation of
      the eye and its functionality.
AB  - PURPOSE: Evaluation of efficacy and safety of proton radiation therapy (PRT) for
      medium- and large-size choroidal melanoma with focus on preservation of the eye
      and its function. METHODS: Retrospective review of 78 patients with 60 medium and
      18 large-size choroidal melanomas at a median follow-up of 34 months. RESULTS:
      The 5-year data for local control, metastases-free survival, and disease-specific
      survival were estimated to be 90.5 +/- 3.7%, 76.2 +/- 6.7%, and 75.6 +/- 7.6%,
      respectively. Eye preservation was achieved in 75.3% of patients, with useful
      (better than 20/200) visual acuity (VA) in 49.1% of surviving patients. Both
      local failure and complications led to enucleation. Prognosticators were tumor
      close to the optic disc (p = 0.003), large tumors involving the ciliary body (p =
      0.041), and local failure (p < 0.001). Prognostic factors for VA following PRT
      were initial VA (p = 0.001), doses to optic disc (p = 0.001) and fovea (p =
      0.022) higher than 35 CGE (Cobalt Gray equivalent), tumor close to the optic disc
      (p = 0.034), and retinal detachment (p < 0.001). Tumor basis diameter was
      significantly related to metastases free survival (p = 0.02), overall survival (p
      = 0.033), and disease specific survival (p = 0.017), but did not impair local
      tumor control, rate of enucleation, and VA. CONCLUSION: The present data suggest
      that PRT is an effective and safe treatment for medium and large size choroidal
      melanoma. PRT can preserve the eye and its function in a reasonable percentage of
      patients. Further evaluation in controlled clinical trials comparing PRT to
      plaque radiotherapy and enucleation is required.

PMID- 11240248
TI  - Perineural spread of cutaneous squamous and basal cell carcinoma: CT and MR
      detection and its impact on patient management and prognosis.
AB  - PURPOSE: To analyze the pretreatment imaging findings and outcome of patients
      with perineural spread of squamous or basal cell carcinoma of the face and scalp
      treated with radiotherapy, to determine whether CT (computed tomography) or MR
      (magnetic resonance) imaging can be effectively used to identify patients who
      would benefit from aggressive treatment, and to characterize the imaging features
      associated with cure. METHODS: Thirty-five patients had perineural spread of
      squamous and basal cell carcinoma along the divisions of the trigeminal and/or
      facial nerves based on clinical findings and/or histopathological proof.
      Perineural extension seen on imaging was divided into three zones of involvement.
      The volume of perineural disease was graded semiquanitatively. All patients
      received radiotherapy with curative intent. RESULTS: Eighteen of the 35 patients
      had imaging evidence of perineural spread of tumor, and the remaining 17 were
      imaging negative for perineural spread. The absolute 5-year survival of the
      imaging positive group was 50% compared with 86% in the imaging-negative group (p
      = 0.048). CONCLUSIONS: Imaging can be used to identify patients with advanced
      perineural spread who warrant aggressive radiotherapy. Imaging evidence of
      perineural invasion worsens prognosis; however, low-volume and peripheral
      perineural disease is radiocurable. Greater perineural tumor volume with more
      central disease was associated with an unfavorable outcome.

PMID- 11240249
TI  - Total body irradiation before allogeneic bone marrow transplantation: is more
      dose better?
AB  - PURPOSE: This study was performed to retrospectively assess the potential
      influence of total-body irradiation (TBI) dose on overall survival in patients
      undergoing allogeneic bone-marrow transplants (BMT) for hematologic malignancies.
      METHODS AND MATERIALS: Between October 1984 and December 1996, 116 patients were
      conditioned with high-dose chemotherapy and fractionated TBI before allogeneic
      BMT. The median age was 34 years (range 3-60). The TBI dose was given in 6
      fractions, twice-a-day, over 3 days before BMT. The total dose was 10 Gy in 24
      patients, 12 Gy in 66 patients, and 13.5 Gy in 26 patients. RESULTS: TBI dose was
      inversely correlated with overall survival. Five-year survival was 62% for
      patients conditioned with 10 Gy, 55% for patients conditioned with 12 Gy, and 46%
      for patients conditioned with 13.5 Gy. Age at BMT was also independently
      correlated with survival, with the best outcome for patients < 40 years old.
      CONCLUSION: A TBI dose (fractionated) > 10 Gy may not necessarily be associated
      with a better outcome in patients undergoing allogeneic bone-marrow transplant
      for hematologic malignancies.

PMID- 11240250
TI  - Hypothalamic/pituitary function following high-dose conformal radiotherapy to the
      base of skull: demonstration of a dose-effect relationship using dose-volume
      histogram analysis.
AB  - PURPOSE: To evaluate the incidence and pattern of hypopituitarism from
      hypothalamic (HT) and pituitary gland (PG) damage following high-dose conformal
      fractionated proton-photon beam radiotherapy (PPRT) to the base of skull (BOS)
      region in adults. The relationship between dose, volume, and PG function is
      explored. METHODS AND MATERIALS: Between May 1982 to October 1997, 107 adults
      with non-PG and non-HT neoplasms (predominantly chordoma and chondrosarcomas) of
      the BOS were treated with PPRT after subtotal resection(s). The median age was
      41.2 years (range, 17-75) with 58 males and 49 females. Median prescribed target
      dose was 68.4 cobalt gray equivalent (CGE) (range, 55.8-79 CGE) at 1.80-1.92 CGE
      per fraction per day (where CGE = proton Gy x 1.1). The HT and PG were outlined
      on planning CT scans to allow dose-volume histograms (DVH) analysis. All patients
      had baseline and follow-up clinical testing of anterior and posterior pituitary
      function including biochemical assessment of thyroid, adrenal, and gonadal
      function, and prolactin secretion. RESULTS: The 10-year actuarial overall
      survival rate was 87%, with median endocrine follow-up time of 5.5 years, thus
      the majority of patients were available for long-term follow-up. Five-year
      actuarial rates of endocrinopathy were as follows: 72% for hyperprolactinemia,
      30% for hypothyroidism, 29% for hypogonadism, and 19% for hypoadrenalism. The
      respective 10-year endocrinopathy rates were 84%, 63%, 36%, and 28%. No patient
      developed diabetes insipidus (vasopressin deficiency). Growth hormone deficiency
      was not routinely followed in this study. Minimum target dose (Dmin) to the PG
      was found to be predictive of endocrinopathy: patients receiving 50 CGE or
      greater at Dmin to the PG experiencing a higher incidence and severity (defined
      as the number of endocrinopathies occurring per patient) of endocrine
      dysfunction. Dmax of 70 CGE or greater to the PG and Dmax of 50 CGE or greater to
      the HT were also predictive of higher rates of endocrine dysfunction. CONCLUSION:
      Radiation-induced damage to the HT & PG occurs frequently after high-dose PPRT to
      the BOS and is manifested by anterior pituitary gland dysfunction.
      Hyperprolactinemia was detected in the majority of patients. Posterior pituitary
      dysfunction, represented by vasopressin activity with diabetes insipidus, was not
      observed in this dose range. Limiting the dose to the HT and PG when feasible
      should reduce the risk of developing clinical hypopituitarism.

PMID- 11240251
TI  - Acute phase response during radiotherapy.
AB  - PURPOSE: The acute phase response is characterized by changes in the plasma
      concentrations of a number of liver-synthesized proteins, one of which is C
      reactive protein (CRP). The existence of these changes in the plasma profile
      underlies the change in erythrocyte sedimentation rate (ESR). Acute phase
      response itself is an illness and may result from immunologic reactions and
      inflammatory processes. This study is designed to determine whether the CRP level
      and ESR increase during radiotherapy and whether their rise correlates with acute
      and late radiation morbidity. METHODS AND MATERIALS: Between April 1997 and
      October 1998, 51 patients with the diagnosis of endometrium and cervical cancer
      were treated with surgery and postoperative radiotherapy. Median age at the time
      of radiotherapy was 52 (range, 26-73) years. Thirty patients received pelvic
      radiotherapy, and 21 patients were treated by pelvic-paraaortic irradiation. A
      total dose of 50.4 Gy to the pelvis and 45 Gy to the paraaortic field were
      delivered in conventional fraction. Erythrocyte sedimentation rates and CRP
      levels were studied before, during, and at the end of radiotherapy. RESULTS: The
      mean ESR measurements before and after radiotherapy were 40 (8-100) and 52 (10
      120), and mean CRP levels were 1.4 (0.12-9.8) and 2.7 (0.12-32.2), respectively.
      The statistical analysis yielded significant rise in ESR and CRP levels at the
      end of radiotherapy (p < 0.001). The increase was more prominent in patients who
      were irradiated through pelvic-paraaortic field than in patients with pelvic
      radiation (p = 0.005 and 0.028 respectively). CONCLUSION: Acute phase response
      was present during radiotherapy. Radiotherapy should be considered as a cause of
      increase in CRP level and ESR especially in clinical conditions where acute phase
      response is important.

PMID- 11240252
TI  - Tumor oximetry: demonstration of an enhanced dynamic mapping procedure using
      fluorine-19 echo planar magnetic resonance imaging in the Dunning prostate R3327
      AT1 rat tumor.
AB  - PURPOSE: We have developed an enhanced approach to measuring regional oxygen
      tension (pO(2)) dynamics in tumors. The technique is demonstrated in a group of 8
      Dunning prostate rat tumors (R3327-AT1) with respect to respiratory challenge.
      METHODS AND MATERIALS: Hexafluorobenzene was injected directly into the tumors of
      anesthetized rats. (19)F nuclear magnetic resonance echo planar imaging
      relaxometry was performed to obtain maps of regional tumor oxygenation under
      baseline conditions and when the inhaled gas was changed to oxygen or carbogen.
      RESULTS: Sequential pO(2) maps required 8 min, with a typical precision of 1-3
      torr at 30-100 individual regions across a tumor. When rats breathed 33% oxygen,
      distinct heterogeneity was observed for baseline oxygenation in each tumor with
      pO(2) values ranging from hypoxic to greater than 100 torr. Larger tumors showed
      significantly lower baseline pO(2). Respiratory challenge with oxygen or carbogen
      produced significant increases in tumor oxygenation with a close correlation
      between the response to each gas at individual locations. Regions of both small
      and large tumors responded to respiratory challenge, but the rate was generally
      much faster in initially well-oxygenated regions. CONCLUSIONS: Regional pO(2) was
      assessed quantitatively and the response of multiple individual tumor regions
      observed simultaneously with respect to interventions.

PMID- 11240253
TI  - Radiation response and cure rate of human colon adenocarcinoma spheroids of
      different size: the significance of hypoxia on tumor control modelling.
AB  - PURPOSE: To evaluate the adequacy of a Poisson tumor control probability (tcp)
      model and the impact of hypoxia on tumor cure. METHODS AND MATERIALS: A human
      colon adenocarcinoma cell line, WiDr, was grown as multicellular spheroids of
      different diameters. Measurements were made of cell survival and spheroid cure
      following 300-kV X-ray external beam irradiation in air and nitrogen. Cell
      survival data were fitted using a two-compartment and an oxygen diffusion model.
      Spheroid cure data were fitted using the tcp model. RESULTS: Hypoxia was seen
      only for spheroids greater than 500 microm in diameter. For small spheroids tcp
      estimates of radiosensitivity and clonogenic number showed excellent agreement
      with experimentally derived values. For large spheroids, although tcp estimates
      of radiosensitivity were comparable with measurements, estimates of the
      clonogenic number were considerably lower than the experimental count.
      Reoxygenation of large spheroids before irradiation resulted in the tcp estimates
      of the number of clonogenic cells agreeing with measured values. CONCLUSIONS:
      When hypoxia was absent, the tcp model accurately predicted cure from measured
      radiosensitivity and clonogen number. When hypoxia was present, the number of
      cells capable of regrowth in situ was considerably lower than the number of
      clonogenic cells that initially survived irradiation. As this counteracted the
      decreased radiosensitivity, hypoxia was less important for cure than predicted
      from cell survival assays. This finding suggests that chronic hypoxia may not
      limit directly the success of radiation therapy.

PMID- 11240254
TI  - Tumor oxygenation after radiotherapy, chemotherapy, and/or hyperthermia predicts
      tumor free survival.
AB  - PURPOSE: To investigate the influence of different treatment modalities
      (radiotherapy, chemotherapy, and hyperthermia) on the oxygenation of human tumor
      xenografts and to correlate it with the tumoricidal effect we conducted this
      study. METHODS AND MATERIALS: Human-derived head-and-neck squamous cell carcinoma
      xenografts (implanted in nude mice/nine groups of 10 mice) were treated with
      various treatment modalities and combinations of them (radiation with 5 x 2 or 10
      x 2 Gy, hyperthermia at 41 degrees C or 41.8 degrees C, chemotherapy with
      ifosfamide [32 mg/kg] or cisplatin [2 mg/kg]). The tumor volume was evaluated 3
      times per week until Day 60. Tumor pO(2) was measured at Day 1, 5, 8, and 12 with
      a polarographic pO(2) histograph. RESULTS: Within treatment time (maximum, 10
      days) the median pO(2) increased in all groups (except the control group),
      concomitantly the fraction of measurements of pO(2) that were less than 10 mm Hg
      showed a constant decrease (p < or = 0.001). The highest difference between the
      median pO(2) values and the fraction of measurements of pO(2) that were less than
      10 mm Hg at the start and 1 week after the end of therapy occurred in the groups
      with radiochemothermotherapy (triple-modality therapy; p< or = 0.001). At Day 60,
      the highest rate of complete remissions was observed in the triple-modality
      therapy groups. CONCLUSION: Tumor oxygenation under a single or combined cancer
      treatment is correlated with treatment efficacy in terms of complete remissions
      at Day 60. The posttherapeutic fraction of measurements of pO(2) that were less
      than 10 mm Hg correlates even better with the long term tumor free survival than
      the median pO(2) values or the pretherapeutic fraction of measurements of pO(2)
      that were less than 10 mm Hg.

PMID- 11240255
TI  - Paclitaxel restores radiation-induced apoptosis in a bcl-2-expressing, radiation
      resistant lymphoma cell line.
AB  - PURPOSE: To restore radiation-induced apoptosis in a bcl-2-expressing, radiation
      resistant murine lymphoma cell line (LY-ar) by pretreatment with paclitaxel
      (Taxol). Because this cell line also has high intracellular levels of glutathione
      (GSH), reportedly due to the bcl-2 expression and involved in the cell's
      antioxidant functions, paclitaxel treatment was correlated with GSH levels.
      METHODS AND MATERIALS: LY-ar cells were pretreated with paclitaxel and then
      irradiated with 5 Gy. Apoptosis was measured by DNA fragmentation 6 h later. Dose
      response and time course experiments were performed. Intracellular GSH levels
      were measured after treatment. Cell survival analysis was performed for various
      paclitaxel concentrations +/- 5 Gy. RESULTS: LY-ar cells pretreated with 0 nM, 10
      nM, 25 nM, and 50 nM paclitaxel for 20 h underwent apoptosis at 2%, 15%, 25%, and
      22%, respectively. With the addition of 5-Gy irradiation, LY-ar cell apoptosis
      increased to 4%, 30%, 49%, and 57%. Maximal apoptosis was detected with a
      paclitaxel pretreatment time of 20 h. Intracellular GSH levels were reduced by
      nearly 50% with paclitaxel pretreatment. Surviving fractions (SFs) with 0 nM, 10
      nM, 25 nM, and 50 nM paclitaxel and 0 Gy were 1.0, 0.50, 0.08, and 0.05,
      respectively. SFs with 0 nM, 10 nM, 25 nM, and 50 nM paclitaxel and 5 Gy were
      0.009, 0.003, 3 x 10(-5), and 1 x 10(-5), respectively. CONCLUSION: Radiation
      induced apoptosis in LY-ar cells was restored by pretreatment with paclitaxel.
      This correlated with lowered levels of intracellular GSH. Cell survival analysis
      indicated that the combination of Taxol and radiation on cell killing was greater
      than additive.

PMID- 11240256
TI  - A phase I study of RSR13, a radiation-enhancing hemoglobin modifier: tolerance of
      repeated intravenous doses and correlation of pharmacokinetics with
      pharmacodynamics.
AB  - PURPOSE: Preclinical studies indicate that RSR13 oxygenates and radiosensitizes
      hypoxic solid tumors by decreasing the oxygen (O(2))-binding affinity of
      hemoglobin (Hb). A Phase I open-label, multicenter dose and frequency escalation
      study was conducted to assess the safety, tolerance, pharmacokinetics, and
      pharmacodynamic effect of daily RSR13 administration to cancer patients receiving
      concurrent palliative radiotherapy (RT). METHODS AND MATERIALS: Eligibility
      criteria included the following: ECOG performance status < or =2; resting and
      exercise arterial oxygen saturation (SaO(2)) > or =90%; an indication for
      palliative RT, 20-40 Gy in 10-15 fractions. RSR13 was administered i.v. via
      central vein over 60 min immediately before RT. Patients received supplemental
      O(2) via nasal cannula at 4 L/min during RSR13 infusion and RT. Plasma, red blood
      cell (RBC), and urine RSR13 concentrations were assayed. The pharmacodynamic
      effect of RSR13 on Hb-O(2) binding affinity was quantified by multipoint
      tonometry and expressed as an increase in p50, defined as the partial pressure of
      O(2) that results in 50% SaO(2). The RSR13 dose in the first cohort was 75 mg/kg
      once a week for two doses; successive cohorts received higher, more frequent
      doses up to 100 mg/kg/day for 10 days during RT. RESULTS: Twenty patients were
      enrolled in the study. Repeated daily doses of RSR13 were generally well
      tolerated. Two adverse events of note occurred: (1) A patient with pre-existing
      restrictive lung disease had transient persistent hypoxemia after the sixth RSR13
      dose; (2) a patient with a recurrent glioma receiving high-dose corticosteroids
      had edema after the seventh RSR13 dose, likely due to the daily high-volume fluid
      infusions. Both patients recovered to baseline status with conservative
      management. Maximum pharmacodynamic effect occurred at the end of RSR13 infusion
      and was proportional to the RBC RSR13 concentration. After an RSR13 dose of 100
      mg/kg, the peak increase in p50 averaged 8.1 mm Hg, consistent with the targeted
      physiologic effect, and then diminished with a half-life of approximately 5 h.
      CONCLUSIONS: RSR13 was well tolerated in daily doses up to 100 mg/kg administered
      for 10 days during RT. The combined administration of RSR13 with 4 L/min
      supplemental O(2) yielded pharmacodynamic conditions in which hypoxic tumor
      radiosensitization can occur. Ongoing Phase II and Phase III studies are
      evaluating the combination of RT and RSR13 for selected indications, including
      primary brain tumors, brain metastases, and non-small-cell lung cancer.

PMID- 11240257
TI  - Single-fraction irradiation has no effect on uptake of radiolabeled pegylated
      liposomes in a tumor xenograft model.
AB  - PURPOSE: These studies were performed with the intention of examining the effect
      of single-fraction doses of radiotherapy (RT) on the tumor deposition of
      radiolabeled pegylated liposomes in an animal xenograft tumor model. METHODS AND
      MATERIALS: Human KB head-and-neck xenograft tumors were established in female
      nude mice. The effect of single fraction tumor RT doses (5, 10, 15, and 20 Gy) on
      the tumor uptake of intravenously administered (111)In-DTPA-labeled pegylated
      liposomes (IDLPL) was examined using two protocols: (1) to test the effect of RT
      delivered 30 min before liposome injection on the time course of tumor uptake
      over a 96-h period; (2) to test the effect of RT at times ranging from 72-h to 1
      h before liposome injection on the levels of liposome uptake at 24 h. Tumor and
      normal tissue/organ (blood, liver, spleen, lung, and kidney) liposome uptake was
      determined by dissection and quantitation in a gamma counter. RESULTS: There was
      no demonstrable effect of RT on tumor uptake of IDLPL (p > 0.1 for all
      comparisons). Reassuringly, neither was there an effect of RT on the
      pharmacokinetics and biodistribution of radiolabeled liposomes to normal tissues.
      CONCLUSIONS: Single fraction doses of RT appear to have no effect on tumor or
      normal tissue biodistribution and pharmacokinetics of radiolabeled pegylated
      liposomes in this animal model.

PMID- 11240258
TI  - A low-pH culture condition enhances the radiosensitizing effect of wortmannin.
AB  - PURPOSE: The radiosensitizing effect of wortmannin on human tumor cells in a low
      pH microenvironment was compared with that in a neutral-pH environment. METHODS
      AND MATERIALS: A172 human glioblastoma cells, A549 human lung adenocarcinoma
      cells, and HMV-1 human melanoma cells were treated with 20 microM wortmannin 2 h
      before irradiation, and cell survival was examined. A low-pH microenvironment was
      simulated by exposing cells to low-pH culture medium for 24 h before wortmannin
      treatment. The effects of wortmannin on the repair of DNA double-strand breaks
      (dsbs) after 50-Gy irradiation in both low- and neutral-pH conditions were
      measured by pulsed-field gel electrophoresis. Expression of the catalytic subunit
      of DNA-dependent protein kinase (DNA-PKcs) in low-pH conditions was also compared
      with that in neutral-pH conditions by Western blot analysis. RESULTS: The
      radiosensitizing effect of wortmannin was greater in low-pH cultures than in
      neutral-pH cultures for all cell lines. The fast-rejoining component of DNA dsb
      repair was inhibited more strongly in low-pH than in neutral-pH conditions,
      although there was little difference in DNA-PKcs expression between groups.
      CONCLUSIONS: The low-pH culture condition, which was designed to mimic the
      microenvironment of the central tumor mass in actively proliferating solid
      tumors, enhanced the radiosensitizing effect of wortmannin by inhibiting the fast
      rejoining component of DNA dsb repair and by prolonging the retention of
      nonrejoined DNA dsbs.

PMID- 11240259
TI  - Cellular responses to ionizing radiation damage.
AB  - PURPOSE: The purpose of this report is to provide current perspectives on studies
      of DNA damage and cell cycle response after ionizing radiation, and their
      applications in radiation oncology. METHODS AND MATERIALS: Presentations at the
      Seventh Annual Radiation Oncology Workshop, held at the International Festival
      Institute at Round Top, TX, were summarized. RESULTS: Eighteen speakers presented
      their current work covering a wide range of studies on cellular responses to
      ionizing radiation. These presentations and discussions form the framework of our
      report. CONCLUSION: In response to ionizing radiation, cells immediately activate
      a series of biochemical pathways that promote cell survival while maintaining
      genetic integrity. The main cellular defense system against ionizing radiation
      exposure is composed of two distinct types of biochemical pathways, that is, the
      DNA damage cell cycle checkpoint pathways and the DNA repair pathways. The DNA
      damage checkpoint pathways are activated directly by DNA damage, while the repair
      pathways are constitutively active and are likely modulated by checkpoint
      signals. Discussions here emphasize that the ATM protein is a central component
      of the ionizing radiation-responsive pyramid and is essential for activating
      divergent molecular responses that involve transcriptional regulation, cell cycle
      arrest, and modulation of DNA repair. The relationship between homologous
      recombinational repair and nonhomologous end joining of double-strand breaks is
      also discussed.

PMID- 11240260
TI  - Late normal tissue injury from permanent interstitial implants.
AB  - PURPOSE: To develop a simple method of calculating biologically effective doses
      in high-dose regions of permanent interstitial implants. METHODS AND MATERIALS:
      The incomplete repair model is used to clarify the relationship between dose, D,
      and biologically effective dose (BED), for permanent interstitial implants. The
      relationship is used to ascertain the BED at high-dose regions that may occur in
      (125)I, (103)Pd, and (198)Au prostate implants. RESULTS: The relationship between
      D and BED is nonlinear and is given by BED(D) = D + D(2)/D(lambda), where
      D(lambda) = [(t(lambda)/t(mu)) + 1](alpha/beta), t(lambda) and t(mu) are the half
      lives of the isotope and of sublethal damage repair respectively, and alpha/beta
      is the alpha:beta ratio. Idealized geometrically identical (125)I, (103)Pd, and
      (198)Au prostate implants with minimum target dose (MTD) of 160 Gy, 120 Gy, and
      64 Gy, respectively, are considered. The BED for (103)Pd and (198)Au will be less
      than the BED for (125)I, for doses up to about 2.5 times the MTD. For higher
      doses, the BED for (103)Pd may be significantly higher than for (125)I.
      CONCLUSION: Permanent interstitial implants using short-lived isotopes may have
      regions with very high biologically effective doses.

PMID- 11240261
TI  - A novel approach to overcome hypoxic tumor resistance: Cu-ATSM-guided intensity
      modulated radiation therapy.
AB  - PURPOSE: Locoregional tumor control for locally advanced cancers with radiation
      therapy has been unsatisfactory. This is in part associated with the phenomenon
      of tumor hypoxia. Assessing hypoxia in human tumors has been difficult due to the
      lack of clinically noninvasive and reproducible methods. A recently developed
      positron emission tomography (PET) imaging-based hypoxia measurement technique
      which employs a Cu(II)-diacetyl-bis(N(4)-methylthiosemicarbazone) (Cu-ATSM)
      tracer is of great interest. Oxygen electrode measurements in animal experiments
      have demonstrated a strong correlation between low tumor pO(2) and excess (60)Cu
      ATSM accumulation. Intensity-modulated radiation therapy (IMRT) allows selective
      targeting of tumor and sparing of normal tissues. In this study, we examined the
      feasibility of combining these novel technologies to develop hypoxia imaging (Cu
      ATSM)-guided IMRT, which may potentially deliver higher dose of radiation to the
      hypoxic tumor subvolume to overcome inherent hypoxia-induced radioresistance
      without compromising normal tissue sparing. METHODS AND MATERIALS: A custom
      designed anthropomorphic head phantom containing computed tomography (CT) and
      positron emitting tomography (PET) visible targets consisting of plastic balls
      and rods distributed throughout the "cranium" was fabricated to assess the
      spatial accuracy of target volume mapping after multimodality image
      coregistration. For head-and-neck cancer patients, a CT and PET imaging fiducial
      marker coregistration system was integrated into the thermoplastic immobilization
      head mask with four CT and PET compatible markers to assist image fusion on a
      Voxel-Q treatment-planning computer. This system was implemented on head-and-neck
      cancer patients, and the gross tumor volume (GTV) was delineated based on
      physical and radiologic findings. Within GTV, regions with a (60)Cu-ATSM uptake
      twice that of contralateral normal neck muscle were operationally designated as
      ATSM-avid or hypoxic tumor volume (hGTV) for this feasibility study. These target
      volumes along with other normal organs contours were defined and transferred to
      an inverse planning computer (Corvus, NOMOS) to create a hypoxia imaging-guided
      IMRT treatment plan. RESULTS: A study of the accuracy of target volume mapping
      showed that the spatial fidelity and imaging distortion after CT and PET image
      coregistration and fusion were within 2 mm in phantom study. Using fiducial
      markers to assist CT/PET imaging fusion in patients with carcinoma of the head
      and-neck area, a heterogeneous distribution of (60)Cu-ATSM within the GTV
      illustrated the success of (60)Cu-ATSM PET to select an ATSM-avid or hypoxic
      tumor subvolume (hGTV). We further demonstrated the feasibility of Cu-ATSM-guided
      IMRT by showing an example in which radiation dose to the hGTV could be escalated
      without compromising normal tissue (parotid glands and spinal cord) sparing. The
      plan delivers 80 Gy in 35 fractions to the ATSM-avid tumor subvolume and the GTV
      simultaneously receives 70 Gy in 35 fractions while more than one-half of the
      parotid glands are spared to less than 30 Gy. CONCLUSION: We demonstrated the
      feasibility of a novel Cu-ATSM-guided IMRT approach through coregistering hypoxia
      (60)Cu-ATSM PET to the corresponding CT images for IMRT planning. Future
      investigation is needed to establish a clinical-pathologic correlation between
      (60)Cu-ATSM retention and radiation curability, to understand tumor re
      oxygenation kinetics, and tumor target uncertainty during a course of radiation
      therapy before implementing this therapeutic approach to patients with locally
      advanced tumor.

PMID- 11240263
TI  - On the determination of an effective planning volume for permanent prostate
      implants.
AB  - PURPOSE: In current practice, planning for prostate brachytherapy is based on the
      state of the prostate at a particular instant in time. Because treatment occurs
      over an extended period, changes in the prostate volume (gland shrinkage) and
      seed displacement lead to disagreement between planned dosimetry to the prostate
      and the dose actually received by the prostate. Discrepancies between planned and
      actual dose to the rectum and urethra also occur. The purpose of this study is to
      investigate the possibility of defining an "effective planning volume" that
      compensates for changes in prostate volume and seed displacement. METHODS AND
      MATERIALS: Waterman's formula is used to estimate prostate shrinkage and seed
      displacement. The prostate volume and potential seed positions at days 0, 6, 12,
      18, 24, and 30 are used in formulating time-dependent dosimetric treatment
      planning models. Both single-period and multi-period models are proposed and
      analyzed. A state-of-the-art computational engine generates unbiased, high
      quality treatment plans in a matter of minutes. Plans are evaluated using
      coverage and conformity indices computed at specific times over a period of 30
      days. The models allow dose to urethra and rectum to be strictly controlled at
      specific instants in time, or throughout the 30-day horizon. RESULTS: For plans
      generated from the single-period models-based on projected prostate volumes and
      potential seed positions on days t = 0, 6, 12, 18, 24, 30, respectively-as t
      increases, the conformity index improves while the coverage worsens. In
      particular, the best coverage and worst conformity are achieved for the plan
      generated using t = 0 (day 0) information. This plan provides over 99% coverage
      over the entire 30-day period, and while it has initial conformity index 1.24,
      the conformity index climbs to 1.58 by day 30. Conversely, the worst coverage and
      best conformity are achieved when the plan is generated using projected
      information from t = 30 (day 30). Plans based on projected data at day 30 yield
      an initial coverage of only 84%, with conformity scores less than 1.34 over the
      entire 30-day period. Among the multi-period plans, with the exception of the two
      period plan obtained using day 0 and projected day 6 data, the average coverage
      is 98% while conformity indices below 1.46 are maintained throughout the 30-day
      horizon. Excessive dose to the urethra and rectum is observed when only day 0
      dosimetric and volumetric data are imposed in the planning procedure. In this
      case, by day 30, 89% of urethra volume receives dose in excess of 120% of the
      remaining prescription dose. Similarly, 40% of rectum volume receives dose in
      excess of the prescribed upper dose bound of 78% of the remaining prescription
      dose. When multi-period dosimetric constraints for urethra and rectum are
      imposed, dose to these structures is controlled throughout the 30-day period.
      CONCLUSIONS: A planning method that takes into account prostate shrinkage and
      seed displacement over time can be used to adjust the balance between coverage
      and conformity. Incorporating projected future volumetric information is useful
      in providing more conformal plans, in some cases improving conformity by as much
      as 21% while sacrificing roughly 7% of initial coverage. Evidence of possible
      morbidity reduction to urethra and rectum via the use of multi-period dosimetric
      constraints on these structures is demonstrated. Among all plans considered, the
      plan obtained via the six-period model provides the best coverage and conformity
      over the 30-day horizon.

PMID- 11240262
TI  - Planning, computer optimization, and dosimetric verification of a segmented
      irradiation technique for prostate cancer.
AB  - PURPOSE: To develop and verify a multisegment technique for prostate irradiation
      that results in better sparing of the rectal wall compared to a conventional
      three-field technique, for patients with a concave-shaped planning target volume
      (PTV) overlapping the rectal wall. METHODS AND MATERIALS: Five patients have been
      selected with various degrees of overlap between PTV and rectal wall. The planned
      dose to the ICRU reference point is 78 Gy. The new technique consists of five
      beams, each having an open segment covering the entire PTV and several smaller
      segments in which the rectum is shielded. Segment weights are computer-optimized
      using an algorithm based on simulated annealing. The score function to be
      minimized consists of dose-volume constraints for PTV, rectal wall, and femoral
      heads. The resulting dose distribution is verified for each patient by using
      point measurements and line scans made with an ionization chamber in a water tank
      and by using film in a cylindrical polystyrene phantom. RESULTS: The final number
      of segments in the five-field technique ranges from 7 to 9 after optimization.
      Compared to the standard three-field technique, the maximum dose to the rectal
      wall decreases by approximately 3 Gy for patients with a large overlap and 1 Gy
      for patients with no overlap, resulting in a reduction of the normal tissue
      complication probability (NTCP) by a factor of 1.3 and 1.2, respectively. The
      mean dose to the PTV is the same for the two techniques, but the dose
      distribution is slightly less homogeneous with the five-field technique (Average
      standard deviation of five patients is 1.1 Gy and 1.7 Gy for the three-field and
      five-field technique, respectively). Ionization chamber measurements show that in
      the PTV, the calculated dose is in general within 1% of the measured dose.
      Outside the PTV, systematic dose deviations of up to 3% exist. Film measurements
      show that for the complete treatment, the position of the isodose lines in
      sagittal and coronal planes is calculated fairly accurately, the maximum distance
      between measured and calculated isodoses being 4 mm. CONCLUSIONS: We developed a
      relatively simple multisegment "step-and-shoot" technique that can be delivered
      within an acceptable time frame at the treatment machine (Extra time needed is
      approximately 3 minutes). The technique results in better sparing of the rectal
      wall compared to the conventional three-field technique. The technique can be
      planned and optimized relatively easily using automated procedures and a
      predefined score function. Dose calculation is accurate and can be verified for
      each patient individually.

PMID- 11240264
TI  - Autoantibodies in atopic dermatitis.
AB  - Recent progress in the autoimmune aspects of atopic dermatitis has clarified that
      patients with atopic dermatitis develop IgE-class autoantibodies mainly against
      intracellular proteins. The cloning of cDNAs encoding autoallergens with human
      expression cDNA libraries and serum IgE from atopic dermatitis patients has
      unraveled the molecular characteristics of IgE-binding autoantigens. Some
      patients with atopic dermatitis also have IgG-class autoantibodies, especially
      anti-nuclear antibodies. One of the nuclear autoantigens was identified as
      DFS70/transcription coactivator p75. In addition, p80-coilin in nuclear coiled
      bodies is also targetted. Several lines of evidence suggest that a subset of
      atopic dermatitis may be associated with an autoimmune response.

PMID- 11240265
TI  - Expression of granulocyte colony-stimulating factor and its receptor in
      epithelial skin tumors.
AB  - Granulocyte colony-stimulating factor receptors (G-CSFR) have been observed on
      the surface of not only hematopoietic cells but also several cancer cells. In the
      present study, we investigated the expression of G-CSFR or G-CSF in epithelial
      skin tumors by immunohistochemical staining. The assessments were defined by the
      percentage of G-CSFR or G-CSF positive cells and expressed as G-CSFR and G-CSF
      scores. The G-CSFR score in SCC (77.6+/-20.0%) was significantly higher than that
      in Bowen's disease (BD) (51.0+/-35.6%), actinic keratosis (AK) (49.3+/-34.6%) or
      normal skin (30.0+/-32.1%) (P=0.0004, P=0.0003, P<0.0001, respectively). The mean
      G-CSF score in SCC (56.7+/-27.4%) or in BD (44.1+/-31.4%) was higher than that in
      normal skin (24.9+/-25.8%) (P=0.0075, P<0.001, respectively). G-CSF expression in
      AK (29.8+/-31.2%) was lower than that in SCC (P=0.0037). There was significant
      positive correlation between the G-CSFR score and the G-CSF score (gamma=0.274,
      P=0.0107) in skin tumors. These findings suggested that the assessment of G-CSFR
      expression might be associated with carcinogenesis of skin tumors.

PMID- 11240266
TI  - Effect of high population density environment on skin barrier function in mice.
AB  - Previous reports have demonstrated that stressful stimuli markedly influenced
      physiological conditions and homeostasis. In this study, we examined the
      influence of high population density environment on barrier function and water
      retention property of skin in mice. Overcrowding stress induced dramatic body
      weight reduction and significant increase in adrenal gland weight. Macroscopic
      skin appearance showed moderate exfoliation and slight wrinkle formation in the
      stress group. Moreover epidermis hyperplasia not concomitant with inflammatory
      reactions such as infiltration of immunocytes and vasodilation was observed in
      the skin from the stress group. Skin surface conductance in the stress group was
      significantly lower than in the control group. On the other hand, transepidermal
      water loss in the stress group increased significantly, compared to the control
      group. Moreover, transdermal penetration of indomethacin and nicotinic acid amide
      was enhanced significantly. These results suggest that overcrowding stress
      induced impairment of barrier function and water retention property. To elucidate
      the mechanism of overcrowding stress-induce dry skin, contents of ceramide and
      pyrrolidone carboxylic acid, which are the important compounds contributing to
      those functions were evaluated. Both of them in stratum corneum declined
      significantly in the stress group. Taken together, these results demonstrate that
      overcrowding stress induced dry skin, and that the impairment of barrier function
      and water retention property correlated with decrease in ceramide and pyrrolidone
      carboxylic acid.

PMID- 11240267
TI  - Inflammation in stasis dermatitis upregulates MMP-1, MMP-2 and MMP-13 expression.
AB  - Stasis dermatitis is a common disorder, which is a consequence of impaired venous
      drainage of the legs. It is characterized histologically by proliferation of
      small blood vessels in the papillary dermis. This neovascularization may lead
      occasionally to the formation of discrete papules due to inflammatory processes.
      In order to evaluate the role of matrix metalloproteinases (MMPs) in the acute
      phase of chronic venous insufficiency, we examined the production of MMP-1, -2, 
      13 and tissue inhibitors of metalloproteinase (TIMP)-1 and -2 in lesional skin of
      stasis dermatitis. A total of 19 patients affected by stasis dermatitis were
      included in this experimental study. Polymerase chain reaction, western blot and
      immunohistochemical studies on tissue specimen were performed. In lesional skin
      of stasis dermatitis, there was elevated gene expression and immunoreactivity for
      MMP-1, -2 and -13 in comparison to healthy controls. In contrast, genexpression
      and immunoreactivity for TIMP-1 and -2 were diminished in stasis dermatitis in
      comparison with healthy controls. Overexpression and production of MMP-1, -2 and 
      13 without inhibitory effects could be the result of cytokine mediated induction.
      Matrix metalloproteinases (MMPs) may play an important role in the remodeling of
      lesional skin in stasis dermatitis.

PMID- 11240268
TI  - The chemotactic effect of a dermal papilla cell-derived factor on outer root
      sheath cells.
AB  - The effect of cultured normal human dermal papilla cells (DPCs) and conditioned
      medium prepared with cultured DPCs on chemotactic migration of human hair outer
      root sheath cells (ORSCs) was examined quantitatively. ORSCs showed significantly
      increased migration toward both cultured DPCs and the conditioned medium
      suggesting that DPCs produce and secrete a paracrine factor(s), which attracts
      hair follicle epithelial cells. Some soluble factors, which are reportedly
      produced by DPCs, such as insulin-like growth factor-I (IGF-I), hepatocyte growth
      factor (HGF), vascular endothelial cell growth factor (VEGF), and transforming
      growth factor-beta1 (TGF-beta1), were also examined. ORSCs showed dramatically
      increased migration toward IGF-I and HGF at concentrations of 1-10 ng/ml. On the
      other hand, neither VEGF nor TGF-beta1 showed any effect on the chemotaxis of
      ORSCs. It is interesting that all factors involving mitogenic activity did not
      always have chemotactic activity for ORSCs. This is the first report to establish
      that IGF-I and HGF have not only a growth stimulatory but also a chemotactic
      effect on ORSCs. In addition, the method presented here may help to simplify
      chemotaxis assays of any type of epithelial keratinocytes with poor mobility.

PMID- 11240270
TI  - Spatial data analysis by epidermal Langerhans cells reveals an elegant system.
AB  - Langerhans cells are dendritic cells situated in the mammalian epidermis. In
      human epidermis, the concentration is between 460 and 1000 mm(-2). Langerhans
      cells fulfill an essential role in skin immune responses. Numerous scientific
      reports on Langerhans cells have appeared, but with no systematic research on the
      pattern of the spatial distributions. On the contrary, in certain fields, a
      spatial distribution is an important theme, and spatial data analysis has a long
      history. We hypothesized that epidermal Langerhans cells were set in the best
      formation for their immuno-surveillance by a sophisticated mechanism. To prove
      this hypothesis, we have imported spatial data analysis into the study of
      epidermal Langerhans cells. Here, we show that the distribution is completely
      regular; the pattern of Voronoi divisions fits the territories; the random
      packing model simulates their bone marrow derivation; a repulsive interaction is
      demonstrated and a repulsive potential function is estimated. Spatial data
      analysis-based computer simulation will be a new method of Langerhans cell study.
      In addition, this procedure shows promise for future distribution research of
      certain cells.

PMID- 11240269
TI  - KF19418, a new compound for hair growth promotion in vitro and in vivo mouse
      models.
AB  - KF19418, a newly synthesized compound, stimulated proliferation of cultured hair
      bulb cells from new born mice in concentration-dependent manner in the range
      under 10 microM. In the culture system of whole skin pieces from 4-week-old mice
      which we earlier established, KF19418 promoted hair follicle elongation as in the
      case of minoxidil. After topical application for 2 weeks of KF19418 or minoxidil
      to dorsal skin of hair-clipped mouse alopecia model, KF19418 at 1% suspension
      accelerated hair regrowth at a rate comparable to 1% minoxidil solution. Thus, it
      was shown that KF19418 directly stimulated hair follicle in vitro and had hair
      growth promoting activities in vivo.

PMID- 11240271
TI  - Expression of CC chemokine receptor 3 on human keratinocytes in vivo and in vitro
      -upregulation by RANTES.
AB  - CC chemokines and their ligands, CC chemokine receptors (CCRs), play an important
      role in the process of inflammation such as trafficking and activating
      inflammatory cells. CCR3 is known to be a ligand for CC chemokines such as
      RANTES, eotaxin and monocyte-chemotactic protein-3 (MCP-3). In this study we
      examined the expression of CCR3 in cultured normal human keratinocytes (KCs).
      CCR3 protein and mRNA expressions were detected in cultured normal KCs by flow
      cytometric (FACS) analysis and reverse-transcription-polymerase chain reaction
      (RT-PCR) analysis. FACS analysis demonstrated that CCR3 expression on KCs was
      significantly upregulated when the cells were cultured with RANTES, but not with
      eotaxin, IL-4 or interferon-gamma. RT-PCR analysis revealed that CCR3 mRNA was
      detectable in normal KCs. We also examined the immunoreactivity of CCR3 in normal
      skin and inflammatory skin lesions. CCR3 was detected weakly in epidermis of
      normal skin, while strong immunoreactivity for CCR3 was seen in epidermis of
      inflammatory skin lesions such as atopic dermatitis. These results suggest that
      CCR3 is constitutively expressed on KCs and is involved in inflammatory
      modulation. RANTES may regulate the function of KCs through CCR3.

PMID- 11240273
TI  - Motor systems neurobiology of behaviour. Web alert.

PMID- 11240274
TI  - Motor systems: understanding motor circuits: where bottom-up meets top-down.

PMID- 11240275
TI  - Motor neuron activity is often insufficient to predict motor response.
AB  - Our understanding of the necessity of considering peripheral properties when
      investigating how neural activity generates behavior has significantly increased
      in recent years. These advances include a theoretical analysis of the
      neuromuscular transform and a deeper understanding of the functional effects of
      non-linear contractile responses, slow muscle relaxation, and neuromodulation.

PMID- 11240276
TI  - The role of short-term synaptic dynamics in motor control.
AB  - During the past few years, much attention has been given to the role of short
      term synaptic plasticity, in particular depression and facilitation, in sculpting
      network activity. A recent study shows that synaptic depression in rhythmic motor
      networks could switch the control of network frequency from intrinsic neuronal
      properties to the synaptic dynamics. Short-term synaptic plasticity is also
      involved in the stabilization and reconfiguration of motor circuits and in the
      initiation, maintenance and modulation of motor programs.

PMID- 11240277
TI  - Motor pattern generation.
AB  - Recent work on the circuits that generate rhythmic movements illustrates the role
      of cotransmitter complement in motor pattern selection and demonstrates that many
      principles first established in invertebrates also hold in vertebrates. Major new
      areas of investigation include the development of central pattern generating
      networks, and the use of mouse mutants.

PMID- 11240278
TI  - Functions of mammalian spinal interneurons during movement.
AB  - The major recent advances in understanding the role of spinal neurons in
      generating movement include new information about the modulation of classic
      reflex pathways during fictive locomotion and in response to pharmacological
      probes. The possibility of understanding movements in terms of spinal
      representations of a basic set of movement primitives has been extended by the
      analysis of normal reflexes. Recordings of the activity of cervical interneurons
      in behaving monkeys has elucidated their contribution to generating voluntary
      movement and revealed their involvement in movement preparation.

PMID- 11240279
TI  - Locomotion and its recovery after spinal injury.
AB  - Recent advances indicate not only that the spinal cord has great potential for
      locomotor recovery after lesion but also that locomotor training can optimise
      this recovery through some form of 'learning'. Improvement of residual function
      can also be achieved through the use of various drugs and treatments such as
      spinal grafts. In spinal-cord-injured humans, a number of recent studies have
      allowed an objective quantification of the improvement of locomotion through
      various forms of training and stimulation.

PMID- 11240280
TI  - Mechanisms of cerebellar learning suggested by eyelid conditioning.
AB  - Classical eyelid conditioning has been used to great advantage in demonstrating
      that the cerebellum helps to improve movements through experience, and in
      identifying the underlying mechanisms. Results from recent studies support the
      hypotheses that learning occurs in both the cerebellar nucleus and cortex, and
      that these sites make different contributions. Specifically, results indicate
      that the cerebellar cortex is responsible for temporally specific learning. A
      combination of experimental and computational studies has been important for
      arriving at these conclusions, which seem to be applicable to the broad range of
      movements to which the cerebellum contributes.

PMID- 11240281
TI  - Complementary 'bottom-up' and 'top-down' approaches to basal ganglia function.
AB  - Recently, two quite different approaches exemplifying 'bottom-up' and 'top-down'
      philosophies have shed new light on basal ganglia function. In vitro work using
      organotypic co-cultures has implicated the subthalamic nucleus (STN) and the
      external segment of the globus pallidus (GP(e)) as pacemakers for low-frequency
      bursting that is reminiscent of the activity produced in Parkinsonian tremor. A
      circuit essential for avian song learning has been identified as part of the
      basal ganglia with surprisingly well conserved cellular details; investigation of
      this system may help to address general issues of basal ganglia function.

PMID- 11240282
TI  - Complementary roles of basal ganglia and cerebellum in learning and motor
      control.
AB  - The classical notion that the basal ganglia and the cerebellum are dedicated to
      motor control has been challenged by the accumulation of evidence revealing their
      involvement in non-motor, cognitive functions. From a computational viewpoint, it
      has been suggested that the cerebellum, the basal ganglia, and the cerebral
      cortex are specialized for different types of learning: namely, supervised
      learning, reinforcement learning and unsupervised learning, respectively. This
      idea of learning-oriented specialization is helpful in understanding the
      complementary roles of the basal ganglia and the cerebellum in motor control and
      cognitive functions.

PMID- 11240283
TI  - The planning and control of reaching movements.
AB  - The notion of internal models has become central to the study of visually guided
      reaching. Armed with this theoretical framework, researchers are gleaning
      insights into long-standing problems in the field, such as the ability to respond
      rapidly to changes in the location of a reach target and the fine control of the
      multi-joint dynamics of the arm. A key factor in these advances is our increased
      understanding of how the brain integrates feedforward control signals, sensory
      feedback, and predictions based on internal models of the arm.

PMID- 11240284
TI  - Coordinate transformations for eye and arm movements in the brain.
AB  - Recent work on the coding of spatial information in the brain has significantly
      advanced our knowledge of sensory to motor transformations on several fronts. The
      encoding of information referenced to the retina (eye-centered) but modulated by
      eye position, called a gain field representation, has proved to be very common
      throughout parietal and occipital cortex. The use of an eye-centered
      representation as a working memory of spatial location is problematic if the eyes
      move during the memory period. Details regarding the manner in which the brain
      solves this problem are beginning to emerge. Finally, the discovery of eye
      centered representations of ongoing or intended arm movements has changed the way
      we think about the order of operations in the sensory to motor coordinate
      transformation.

PMID- 11240286
TI  - Path integration in insects.
AB  - The most notable advance in our knowledge of path integration in insects is a new
      understanding of how the honeybee measures the distance that it travels during
      its foraging trips. Data from two groups show that the bee's odometer records
      distance in terms of the net amount of image motion over the retina that is
      accumulated during a flight. Progress has also been made in clarifying the
      relation between path integration and other navigational strategies. On
      unfamiliar ground, path integration is the only available means of navigation. In
      familiar surroundings, however, guidance by landmarks may override guidance by
      path integration. Path integration then becomes a back-up strategy that is used
      primarily when landmarks fail.

PMID- 11240287
TI  - Who, what, where? Recognition and localization of acoustic signals by insects.
AB  - Insects, like all hearing animals, must analyze acoustic signals to determine
      both their content and their location. Neurophysiological experiments, together
      with behavioral tests, are beginning to reveal the mechanisms underlying these
      signal-analysis tasks. Work summarized here focusses on two issues: first, how
      insects analyze the temporal structure of a single signal in the presence of
      other competing signals; and second, how the signal's location is represented by
      the binaural difference in neural activity.

PMID- 11240288
TI  - The hippocampus and memory: a comparative and ethological perspective.
AB  - During the past year, considerable progress has been made in our understanding of
      the wide-ranging functions of the hippocampus. Highlights include the development
      of new tasks with which to assess spatial/topographic memory in humans and
      monkeys, novel tests of relational memory in rats, and episodic-like memory tasks
      in birds. In addition, novel theories of hippocampal function have been developed
      that are notable for their applicability to both humans and animal models.

PMID- 11240289
TI  - Chasing fate and function of new neurons in adult brains.
AB  - Neuron production, migration and differentiation are major developmental events
      that continue, on a smaller scale, into adult life in a wide range of species
      from insects to mammals. Recent reports of adult neurogenesis in primates,
      including humans, have led to explosive scientific and public attention. During
      the last two years, significant discoveries have revealed that the generation,
      recruitment and survival of new neurons in adult brains are governed by
      principles similar to those that shape the developing brain, such as neuronal
      death, sensory experience, activity levels, and learning. Similarly, many factors
      implicated in embryonic neurogenesis are increasingly found to regulate adult
      neurogenesis and survival as well. These findings now allow the first
      manipulations of the numbers of adult-generated neurons to address their
      potential behavioral function.

PMID- 11240290
TI  - Neuropeptides and the evolution of social behavior.
AB  - Comparative studies over the past year have revealed two new insights into the
      role of neuropeptides in the evolution of social behaviors. First, across
      vertebrate taxa, certain neuropeptide effects appear to be gender-specific.
      Second, species variations in receptor gene structure can alter neuropeptide
      receptor distribution and thereby contribute to species differences in social
      behavior.

PMID- 11240291
TI  - Behavioral functions of the insect mushroom bodies.
AB  - New methods of intervention in Drosophila and other insect species reveal that
      the mushroom bodies are involved in a diverse set of behavioral functions. The
      intrinsic Kenyon cells (those neurons with projections within the mushroom
      bodies) house part of the short-term memory trace for odors and are required for
      courtship conditioning memory. A pair of extrinsic mushroom body neurons (neurons
      with projections both inside and outside the mushroom bodies) provides a
      neuropeptide important for 1-hour olfactory memory. In addition, the mushroom
      bodies are necessary for context generalization in visual learning and for
      regulating the transition from walking to rest.

PMID- 11240292
TI  - Early post-traumatic acute respiratory distress syndrome and albumin excretion
      rate: a prospective evaluation of a 'point-of care' predictive test.
AB  - All patients sustaining major trauma exhibit increased capillary permeability,
      manifested as micro-albuminuria. Urinary albumin excretion rate (AER) measured on
      intensive care units (ICU) can predict early post-traumatic acute respiratory
      distress syndrome (ARDS). This prospective study sought to evaluate AER as a
      practical predictive test for early ARDS. Staff at the participating centres were
      trained in the use of the Behring Turbitimer and the concept of AER as a
      predictor of early post-traumatic ARDS. AER was measured every 2 h for the first
      24 h, on 54 adult blunt trauma admissions (ISS>/=18). A diagnosis of early acute
      lung injury (ALI) or ARDS was made using the American-European Consensus
      Conference criteria. Eleven patients developed ARDS, ten developed ALI, and 23
      had no pulmonary dysfunction. The AER was significantly greater in those who
      developed ARDS 8 and 18 h after admission. The positive predictive value of the
      test was 64% at 8 h, the negative predictive power 73%. The test was performed
      most consistently in the middle 10 h of the study period. If intervention had
      been based on the 8 h data point result, 75% patients who had the test performed
      and later developed ARDS would have had intervention appropriately. In principle,
      testing for AER as a predictor of post-traumatic ARDS on ICU is feasible,
      however, this study has underlined the challenges of introducing new concepts
      into the ICU environment.

PMID- 11240293
TI  - Applying the Quebec Task Force criteria as a frame of reference for studies of
      whiplash injuries.
AB  - Research prior to 1995 showed a diversity of either inclusion or exclusion
      criteria (or both) for diagnosing whiplash injury. As a consequence, the Quebec
      Task Force (QTF) developed expert-based criteria, which may be considered as a
      the 'new' gold standard. Here, we examined the inclusion criteria and exclusion
      criteria used in research populations from the major 82 research studies
      performed during the period 1980-1998, comparing their similarities and
      dissimilarities to the QTF standard. None of the articles satisfied the QTF
      definitions completely, either before or after their introduction in 1995.
      Nevertheless, the QTF still seems to have had some impact on either the published
      inclusion or exclusion criteria. We observed that both sets of criteria showed a
      qualitative shift following the QTF publication in 1995. For the inclusion
      criteria, we found both a statistically significant increase in use of the QTF
      definition (acceleration-deceleration mechanism, rear-end collision, motor
      vehicle collision or other mishaps) and in the criterion 'neck pain'. We also
      observed some smaller changes in both inclusion and exclusion criteria but none
      of these was significant statistically.

PMID- 11240294
TI  - Acute central cervical cord injury: the effect of age upon prognosis.
AB  - In this clinical study, a total of 89 consecutive patients with acute cervical
      cord injury was analysed retrospectively. There were 29 patients aged 60 years
      and over, accounting for 32.6% of all the cases. All the patients were followed
      up from 1 to 15 years, with an average of 6 years and 4 months. Among the
      patients of 60 years and over, 27 (93.1%) had both upper and lower extremities
      involved, compared with 40 (66.7%) of those under 60 years (P<0.05). Also among
      the older group, 24 had radiographic findings of severe cervical spinal
      degeneration, a higher incidence than in the patients under 60 years (P<0.05).
      There were two deaths in patients of 60 years and older. The average American
      Spinal Injury Association (ASIA) scores in both the younger and older groups at
      final follow-up were significantly larger (P<0.01) than on admission, but the age
      of the patients was negatively correlated with the ASIA scores both on admission
      (P<0.05) and at final follow-up (P<0.01). The ASIA score was significantly lower
      (P<0.01) in patients aged 60 years and over than in those younger than 60 years
      both on admission and at final follow-up. Patients aged 60 years and over with
      acute central cervical cord injury have a poorer prognosis although they may
      experience significant neurological improvement.

PMID- 11240295
TI  - Blunt abdominal aortic trauma in association with thoracolumbar spine fractures.
AB  - All patients with blunt abdominal aortic disruption (BAAD) in the trauma
      registries at the three Regional Trauma Centres were retrospectively reviewed
      over the last decade. From the 11465 trauma admissions ISS>16,194 sustained
      aortic injuries. Eight cases of BAAD were identified, six with concurrent
      thoracolumbar spine (TLS) fractures (mean ISS 42). Patients with BAAD and TLS
      were subject to a detailed analysis. Clinically, three injury types were seen,
      hemodynamically unstable (uncontained full thickness laceration), stable
      symptomatic (intimal dissection with occlusion), and stable asymptomatic
      (contained full thickness laceration or intimal dissection without occlusion).
      All spinal column fractures involved a distractive mechanism, one with both
      distractive and translational fracture components. We propose that a distractive
      force, applied to the aorta lying anterior to the anterior longitudinal ligament,
      results in an aortic injury spectrum ranging from an intimal tear to a full
      thickness laceration, as a related injury. Computed tomography (CT) was an
      important imaging modality in the stable asymptomatic patients. All intimal
      dissections without occlusion were managed non-operatively. With distractive TLS
      fractures, BAAD needs to be considered.

PMID- 11240296
TI  - Internal fixation of children's fractures using the Fixclip system.
AB  - Thirty five fractures were treated using the Fixclip (Corin medical) system of
      wires and retaining clips. Union occurred in all instances. In the region of the
      growth plate, the implant enabled small fragments of bone to be captured and the
      epiphysis to be secured to the metaphysis without transgression of the physis. In
      the case of metaphyseal and diaphyseal injuries, the Fixclip allowed
      stabilisation of fractures with minimal disturbance of the fracture site and soft
      tissues. This combined with the flexibility inherent in the construct encourages
      secondary healing with the formation of abundant external callus. On four
      occasions, a wire escaped from the clip although this led to further intervention
      in only one instance. In each of these cases, a single retaining clip had been
      used suggesting that at least two clips should be used for each construct.

PMID- 11240297
TI  - Classification of posterior fracture dislocation of the hip joint: a modification
      of the Thompsen Epstein classification.
AB  - The purpose of this paper was to describe a classification of posterior fracture
      dislocations of the hip joint, which would highlight the important aspects of
      managing this injury and more closely correlate with the prognosis. During the
      period from July 1994 to September 1997, the senior author operated on 60
      posterior fracture dislocations of the hip joint. The results of the surgery were
      scored according to our ability to accurately anatomically reconstruct the
      acetabulum. We found that the degree of comminution was a greater determent of
      whether we could achieve an anatomical reconstruction than the presence of an
      associated acetabular floor fracture. Epstein showed conclusively that type II
      and III injuries have significantly different outcomes, but then grouped them
      together as type IV injuries if there was an associated floor fracture. We felt
      it more appropriate to continue with Epstein's fundamental feature of ascribing a
      grade according to the comminution and subdivided his type IV injuries.

PMID- 11240298
TI  - Is the mechanism of traumatic posterior dislocation of the hip a brake pedal
      injury rather than a dashboard injury?
AB  - This study proposes that the mechanism of traumatic posterior dislocation of the
      hip (TPDH) is a brake pedal injury rather than a dashboard injury. A total of 168
      cases of TPDH were treated during the past 10 years. Clinical records of 48
      patients, who were drivers and suffered from a head-on collision accident, were
      examined. The right hip was involved in 45 cases. A total of 31 cases were not
      accompanied by knee injuries. In 11 cases with foot or ankle injuries and right
      hip dislocation, 10 had right foot or ankle injuries. If the mechanism of TPDH
      was a dashboard injury, the left hip would be involved more frequently and there
      would be more knee injuries. Our hypothesis about the mechanism is that, in a
      head-on collision, the driver presses desperately on the brake pedal with his
      right hip slightly flexed, adducted and internally rotated.

PMID- 11240299
TI  - Biomechanical factors and failure of transcervical hip fracture repair.
AB  - OBJECTIVE: To assess the association between biomechanical measurements (bone
      quality of the femoral neck, comminution, fracture angle, and fracture level) and
      the likelihood of fixation failure among patients who have a multiple screw
      stabilisation of an intracapsular hip fracture. METHODS: A cohort study of 139
      Washington State residents greater than 60 years of age who sustained a fall
      related transcervical hip fracture treated from 1990 to 1996 inclusive.
      Measurements of bone quality, fracture angle, fracture level, and comminution
      were taken from perioperative X-rays. The outcome measure was clinical failure of
      the internal fixation procedure within 12 months of hospital discharge, as
      measured by readmission for further surgery to that hip. RESULTS: Of the four
      biomechanical aspects examined, only bone quality, as measured by presence of an
      ICD code for osteoporosis, was significantly associated with risk of subsequent
      hospitalisation for revision surgery (adjusted hazard ratio 7.7, 95% CI 1.8
      32.8). CONCLUSION: A diagnosis code for osteoporosis was related to the outcome
      of intracapsular fractures repaired with multiple pins. Other biomechanical
      measurements from diagnostic X-rays were not related to the need for further
      surgery.

PMID- 11240300
TI  - Percutaneous plating of the low energy unstable tibial plateau fractures: a new
      technique.
AB  - We discuss the management of two low-energy unstable tibial plateau fractures in
      this report, and describe our new technique of percutaneous plating to stabilise
      these fractures. This minimally invasive surgery has the obvious advantages to
      the traditional open reduction and internal fixation and the non-operative
      management by plaster immobilisation. Stable fixation can be achieved by small
      fragment plates used in this technique allowing safe mobilisation. This novel
      method of internal fixation could be a useful inclusion in the armamentarium for
      the management of tibial plateau fractures and can be safely practised by an
      orthopaedic surgeon at a District General Hospital.

PMID- 11240301
TI  - Intramedullary nailing in the treatment of aseptic tibial nonunion.
AB  - Fifty patients suffering from aseptic tibial nonunion underwent reamed
      intramedullary nailing (I.N.) and were retrospectively reviewed. Thirty-six
      patients were initially treated with external fixation, six with plate and
      screws, one with a static I.N., and seven with plaster of Paris. Eighteen of the
      fractures were initially open (A: 5, B: 6, and C: 7 according to the Gustilo
      classification). In 34 cases a closed procedure was performed, whereas in
      sixteen, an opening at the nonunion site was unavoidable either to remove
      metalwork or realign the fragments. Following failed external fixation, secondary
      I.N. was performed at least 10 days after removal of the device. Bone grafts from
      the iliac crest were used in three cases, and a fibular osteotomy was performed
      in 33. Patients were followed up for an average of 2.5 years after nailing,
      ranging from 10 months to 7 years. A solid union was achieved in all patients
      within a period of 6 months. One patient developed late infection, which settled
      after nail removal and one patient developed impending compartment syndrome which
      was detected on the first post-operative day and was treated with a fasciotomy.
      Transient peroneal nerve palsy occurred in one patient and this recovered in 3
      months, whereas in nine patients a clinically acceptable deformity was noticed.
      In conclusion, we believe that reamed intramedullary nailing is a highly
      effective treatment for aseptic tibial nonunions. Early and late complications
      are rare and bone graft is rarely needed. The method allows early weight bearing
      even before solid union occurs, short hospitalisation time and early return to
      work without external support.

PMID- 11240302
TI  - Fine wire frame arthrodesis for the salvage of severe ankle pathology.
AB  - Ankle arthrodesis is an accepted method of treatment for severe ankle pathology,
      but no single method of treatment is universally successful. Compression is
      usually applied across the ankle joint and maintained with either internal or
      external fixation; both are associated with complications such as infection, non
      union and pain. We present our experience of 13 difficult cases managed by fine
      wire external frames, and describe the surgical technique used.A sound
      arthrodesis was achieved in 12 out of 13 cases, though one case required a repeat
      procedure, giving a union rate of 92% of cases or 86% of procedures. The mean
      period of fixation was 24 weeks (range 12-82), followed by a mean period of cast
      immobilisation of 7 weeks (range 0-10). Using Mazur's functional ankle score
      there were seven good results, four fair, one poor and one failure, which
      resulted in a below knee amputation. We believe this method represents a
      significant improvement on previously published results, but accept that it
      requires considerable experience and should not be considered for primary ankle
      arthrodesis. We would recommend its usage for the salvage of failed arthrodesis
      or severe fracture non-union, particularly in the presence of infection.

PMID- 11240303
TI  - Sand blast injury.

PMID- 11240304
TI  - Vertex epidural haematoma presented with paraplegia.

PMID- 11240305
TI  - Multiple thoracic spine wedge fractures with associated sternal fracture; an
      unstable combination.

PMID- 11240306
TI  - False aneurysm of the brachial artery in supracondylar fracture treated with
      Kirschner wire fixation: a case report.

PMID- 11240307
TI  - Zinc in the retina.
AB  - Experimental evidence exists to suggest that zinc can have positive and negative
      effects on the physiology of cells depending on the "local" concentration,
      localisation (extracellular vs. intracellular) and/or state (bound vs. free). The
      retina contains particularly high amounts of zinc suggesting a pivotal role in
      the tissue. There is also suggestive evidence that zinc deficiency in humans may
      result in abnormal dark adaptation and/or age-related macular degeneration. The
      purpose of this article is to provide an overview of various proposed functions
      for zinc, particularly in the retina. Endogenous chelatable zinc in the retina is
      localised mainly to the photoreceptors and retinal pigment epithelial cells.
      Moreover, the zinc localisation in the photoreceptors varies in dark and light,
      suggesting a role for zinc in a light-regulated process. Some zinc is also
      located to other areas of the retina but clearly defined zinc-enriched neurones
      could not be identified as has been shown to occur in certain areas of the brain.
      Neurones post-synaptic to zinc-enriched neurones in the brain have been suggested
      to be particularly vulnerable in ischaemia. The role of zinc in retinal ischaemia
      has been investigated to determine how it is involved in the process. It would
      appear that when zinc is administered in low concentrations it generally has a
      positive effect on an insulted retina as in ischaemia. However, higher
      concentrations of zinc exacerbates the influence of the insult and also acts as a
      toxin. Use of zinc supplements in diet must, therefore, be taken with caution.

PMID- 11240308
TI  - Estrogen receptors in the human forebrain and the relation to neuropsychiatric
      disorders.
AB  - The steroid hormone estrogen influences brain function and neuropsychiatric
      disorders, but neuroanatomical information about the estrogen receptors (ERs) are
      rather limited. The main focus of this article is to provide an overview of the
      current status of the ER distribution and possible function in the human brain.
      The ERs are ligand activated transcription factors that belong to the steroid
      hormone receptors, included in the nuclear receptor superfamily. To date, there
      are two known ER subtypes, alpha and beta. In the human forebrain, both estrogen
      receptor subtypes are predominantly expressed in limbic-related areas, although
      they show distinct distribution patterns. The ERalpha mRNA expression appears to
      dominate in the hypothalamus and amygdala, indicating that the alpha-subtype
      might modulate neuronal cell populations involved in autonomic and reproductive
      neuroendocrine functions as well as emotional interpretation and processing. In
      contrast, the hippocampal formation, entorhinal cortex, and thalamus appear to be
      ERbeta dominant areas, suggesting a putative role for ERbeta in cognition, non
      emotional memory and motor functions. Clinical observations of estrogenic effects
      together with the information available today regarding ER expression in the
      primate brain provide important clues as to the functional aspects of the two ER
      subtypes. However, further characterization of the different phenotypes of the ER
      expressing cells in the human brain is needed as well as the delineation of the
      genes which are regulated by the ERs and how this transcriptional control
      correlates with human behavior and mental status.

PMID- 11240309
TI  - The weaver mutant mouse: a model to study the ontogeny of dopamine transmission
      systems and their role in drug addiction.
AB  - Dopaminergic neurons and their projection-systems are important in some
      fundamental human activities like locomotion, feeding and sex, essential for
      survival and procreation, and are relevant to pathologies like Parkinson's
      disease and drug abuse. Three main dopaminergic projection-systems, namely the
      nigrostriatal, mesocortical and mesolimbic pathways are the major targets of the
      neuropharmacological actions of psychomotor stimulants such as cocaine and
      amphetamine. Studies on knockout mice for dopamine or its receptors provide
      substantial information but fail to reveal the role of individual dopaminergic
      projection-systems. Mutant animals with defects specific to one or more
      projection-systems might be useful for studying the role of individual
      dopaminergic projection-systems. We propose the weaver mutant mouse, with a
      defective nigrostriatal dopaminergic projection-system and dopamine depletion in
      the dorsal striatum but with intact mesocorticolimbic projection-systems, as a
      suitable model to study the role of individual dopaminergic systems in diverse
      biological processes including Parkinson's disease and drug abuse.

PMID- 11240310
TI  - Voltage-gated proton channels in microglia.
AB  - Microglia, macrophages that reside in the brain, can express at least 12
      different ion channels, including voltage-gated proton channels. The properties
      of H+ currents in microglia are similar to those in other phagocytes. Proton
      currents are elicited by depolarizing the membrane potential, but activation also
      depends strongly on both intracellular pH (pH(i)) and extracellular pH (pH(o)).
      Increasing pH(o) or lowering pH(i) promotes H+ channel opening by shifting the
      activation threshold to more negative potentials. H+ channels in microglia open
      only when the pH gradient is outward, so they carry only outward current in the
      steady state. Time-dependent activation of H+ currents is slow, with a time
      constant roughly 1 s at room temperature. Microglial H+ currents are inhibited by
      inorganic polyvalent cations, which reduce H+ current amplitude and shift the
      voltage dependence of activation to more positive potentials. Cytoskeletal
      disruptive agents modulate H+ currents in microglia. Cytochalasin D and
      colchicine decrease the current density and slow the activation of H+ currents.
      Similar changes of H+ currents, possibly due to cytoskeletal reorganization,
      occur in microglia during the transformation from ameboid to ramified morphology.
      Phagocytes, including microglia, undergo a respiratory burst, in which NADPH
      oxidase releases bactericidal superoxide anions into the phagosome and
      stoichiometrically releases protons into the cell, tending to depolarize and
      acidify the cell. H+ currents may help regulate both the membrane potential and
      pH(i) during the respiratory burst. By compensating for the efflux of electrons
      and counteracting intracellular acidification, H+ channels help maintain
      superoxide anion production.

PMID- 11240311
TI  - Vasopressin- and oxytocin-induced activity in the central nervous system:
      electrophysiological studies using in-vitro systems.
AB  - During the last two decades, it has become apparent that vasopressin and
      oxytocin, in addition to playing a role as peptide hormones, also act as
      neurotransmitters/neuromodulators. A number of arguments support this notion: (i)
      vasopressin and oxytocin are synthesized not only in hypothalamo-neurohypophysial
      cells, but also in other hypothalamic and extrahypothalamic cell bodies, whose
      axon projects to the limbic system, the brainstem and the spinal cord. (ii)
      Vasopressin and oxytocin can be shed from central axons as are classical
      neurotransmitters. (iii) Specific binding sites, i.e. membrane receptors having
      high affinity for vasopressin and oxytocin are present in the central nervous
      system. (iv) Vasopressin and oxytocin can alter the firing rate of selected
      neuronal populations. (v) In-situ injection of vasopressin and oxytocin receptor
      agonists and antagonists can interfere with behavior or physiological
      regulations. Morphological studies and electrophysiological recordings have
      evidenced a close anatomical correlation between the presence of vasopressin and
      oxytocin receptors in the brain and the neuronal responsiveness to vasopressin or
      oxytocin. These compounds have been found to affect membrane excitability in
      neurons located in the limbic system, hypothalamus, circumventricular organs,
      brainstem, and spinal cord. Sharp electrode intracellular recordings and whole
      cell recordings, done in brainstem motoneurons or in spinal cord neurons, have
      revealed that vasopressin and oxytocin can directly affect neuronal excitability
      by opening non-specific cationic channels or by closing K(+) channels. These
      neuropeptides can also influence synaptic transmission, by acting either
      postsynaptically or upon presynaptic target neurons or axon terminals. Whereas,
      in cultured neurons, vasopressin and oxytocin appear to mobilize intracellular
      Ca(++), in brainstem slices, the action of oxytocin is mediated by a second
      messenger that is distinct from the second messenger activated in peripheral
      target cells. In this review, we will summarize studies carried out at the
      cellular level, i.e. we will concentrate on in-vitro approaches. Vasopressin and
      oxytocin will be treated together. Though acting via distinct receptors in
      distinct brain areas, these two neuropeptides appear to exert similar effects
      upon neuronal excitability.

PMID- 11240313
TI  - Vagal cardiac control throughout the day: the relative importance of effort
      reward imbalance and within-day measurements of mood, demand and satisfaction.
AB  - The effects of variables derived from a work stress theory (the effort-reward
      imbalance theory) on the power in the high frequency (HF_HRV) band of heart rate
      (0.14-0.40 Hz) throughout a work day, were determined using multilevel analysis.
      Explanatory variables were analysed at two levels: at the lowest level (within
      day level), the effects of positive mood, negative mood, demand, satisfaction,
      demand-satisfaction ratio, and time of day were assessed. At the highest level
      (the subject level), the effects of sleep quality, effort, reward, effort-reward
      imbalance, need for control, type of work (profession), negative affectivity,
      gender and smoking on HF_HRV were assessed. Need for control has a negative
      effect on HF_HRV after controlling for time of day effects, i.e. subjects with a
      high need for control have a lower vagal control of the heart. In the long run,
      these subjects may be considered to be at increased health risk, because they
      have less of the health protective effects of vagal tone. The interaction between
      effort-reward imbalance and time of day has a positive effect on HF_HRV, i.e. the
      cardiac vagal control of subjects with a high effort-reward imbalance increases
      as the day progresses. It is discussed that this probably reflects reduced effort
      allocation, ensuing from disengagement from the work demands.

PMID- 11240312
TI  - Anticholinergicity and cognitive processing in chronic schizophrenia.
AB  - Patients with chronic schizophrenia suffer from alterations in cholinergic
      functioning due to several factors, including the disease diathesis and
      pharmacologic treatments. Acetylcholine-cognition relationships are well explored
      in normals but are unclear in schizophrenia. Prior work indicated serum
      anticholinergicity does not cause global cognitive impairment in this group
      (Tracy et al., 1998a), raising the possibility that anticholinergicity normalizes
      an abnormal hyperactive cholinergic state. Serum anticholinergic levels were
      determined in 38 chronic schizophrenia patients using an established
      radioreceptor assay method. Six cognitive functions associated with cholinergic
      tone in normals were tested. The potential role of autonomic arousal and
      cigarette smoking were also assessed as both have been linked to cholinergic
      functioning. Regression analyses showed measures of inhibitory executive control
      and effortful memory accounted for a greater proportion of the variance in the
      anticholinergicity measure compared to the other variables. The data demonstrate
      a relationship between high anticholinergicity and worse performance on two types
      of attention-resource demanding cognitive processes and do not support the notion
      that reduced cholinergic tone normalizes a hyperactive cortical acetylcholine
      substrate. Relevant neuroanatomic structures and implications for models of
      cognitive deficits in schizophrenia are discussed.

PMID- 11240314
TI  - What is learned in patterning discriminations? Further tests of configural
      accounts of associative learning in human electrodermal conditioning.
AB  - Two Pavlovian SCR conditioning experiments investigated positive and negative
      patterning discriminations in humans by means of transfer tests. In Experiment 1,
      positive patterning (A-,B-,AB+) was trained interleaved with non-reinforced
      presentations of an additional stimulus (C-). Then responding to new compounds
      consisting of either already trained elements (AC,BC) or new elements (DE) was
      examined. In Experiment 2, negative patterning (A+,B+,AB-) was trained
      interleaved with reinforced presentations of an additional stimulus (C+). Again,
      we examined responding to new compounds consisting of either already trained
      elements (AC,BC) or new elements (DE). In both experiments the initial patterning
      discrimination was solved successfully. The response patterns to the test
      compounds in both experiments were in contradiction to configural accounts of
      associative learning. In positive patterning human participants seemed to utilize
      'number' or some other abstract feature in preference to available concrete
      stimuli. In negative patterning the abstract dimension of 'separate-versus
      together' or 'opposite' was used.

PMID- 11240315
TI  - Abstracts of the 7th annual meeting of the International Society for the
      Advancement of Respiratory Psychophysiology (ISARP).

PMID- 11240316
TI  - Delayed facial palsy after vestibular schwannoma surgery.
AB  - OBJECTIVE: there is a lack of uniformity in the literature of the definition of
      delayed facial palsy (DFP) after vestibular schwannoma surgery. The aim of this
      study was to attempt to provide a clear definition of this clinical entity.
      METHODS: a prospective study was undertaken of all patients, with an intact
      facial nerve postoperatively, undergoing vestibular schwannoma surgery during a
      16-month period. Delayed facial palsy was defined as any worsening of facial
      function after the initial assessment of postoperative function. RESULTS: a total
      of 67 patients, operated on between February 1994 and June 1995 satisfied the
      requirements of the study. Eight of the 67 patients developed a worsening of
      facial function after the first postoperative day. There were three males and
      five females with an age range of 29-73 years (mean, 53 years). CONCLUSION: DFP
      should be defined as any deterioration of facial function after vestibular
      schwannoma surgery.

PMID- 11240317
TI  - Prognosis of acute acoustic trauma: a retrospective study using multiple logistic
      regression analysis.
AB  - OBJECTIVE: The prognosis for acute acoustic trauma (AAT) is difficult to predict.
      Multiple logistic regression analysis was used in this study to determine which
      factors were most strongly related to outcome for patients with AAT. METHODS: The
      study group was comprised of 52 patients (52 ears). Separate analyses were
      performed on the no change and partial recovery groups, and on the no change and
      full recovery groups. The following eight factors were examined as explanatory
      variables, age; number of days before the start of treatment; use of earplugs;
      drug therapy (adrenocortical hormones, low molecular weight dextrans, and vitamin
      B12), mean hearing levels at 0.5, 1, and 2 kHz (pure tone average, PTA), and mean
      hearing levels at 4 and 8 kHz (high tone average, HTA). RESULTS: Factors
      determined to be most strongly related to outcome were the number of days before
      the start of treatment, PTA, and HTA. No significant relation to outcome was
      determined for the five following factors, age; use of earplugs; and drug therapy
      (adrenocortical hormones, low molecular weight dextrans, and vitamin B12).
      CONCLUSION: Our results will increase the ability to prognosticate the outcome
      for AAT.

PMID- 11240318
TI  - Tubal compliance--changes with age and in tubal malfunction.
AB  - OBJECTIVE: It is known that eustachian tubal compliance has influence on the
      tubal function. We applied the direct measurement method to ascertain whether or
      not aging and tubal diseases are related to the compliance of the cartilaginous
      part of the eustachian tube. METHODS: We developed a method for directly
      measuring tubal compliance by inserting a balloon catheter, which is inflated
      with water, into the eustachian tube and comparing the change in balloon pressure
      with the balloon volume. This method is advantageous in that one can directly
      measure tubal compliance in the cartilaginous part of the eustachian tube. Using
      this method we examined tubal compliance in 16 normal young volunteer ears, 21
      normal elderly volunteer ears, 11 elderly ears with patulous tube and 12 elderly
      ears with stenotic tube including otitis media with effusion. RESULTS: In adults
      the tubal compliance increases in value with age. Tubal compliance of the elderly
      patulous tube was significantly higher than that of the normal elderly one, on
      the other hand the compliance of the elderly stenotic tube was significantly
      lower than that of the normal one. CONCLUSION: Tubal compliance was considered to
      be changed with aging and influence of the patulous and stenotic tubes.

PMID- 11240319
TI  - Surgical strategy for cholesteatoma in children.
AB  - OBJECTIVE: We reviewed our experience with childhood cholesteatoma in children
      under 15 years old. Based on cumulative postoperative data, we propose a modified
      canal-wall-up technique in conjunction with a planned, staged operation. METHODS:
      From 1982 to 1997, 56 children with cholesteatoma (58 ears, total) underwent
      surgery in our department. In the early period (1982-1990), canal wall-down
      mastoidectomy was performed in 52% (21 of 40 ears), and canal wall-up
      mastoidectomy in 48% (the remaining 19 ears). In the late period (1991-1997), 18
      ears with cholesteatoma underwent surgery. The canal-wall up mastoidectomy was
      performed in 89% (16 ears), and canal-wall-down mastoidectomy in the remaining
      11% (two ears). RESULTS: In the early period (1982-1990), cholesteatoma recurred
      more frequently in the canal-wall-up mastoidectomy group than in the canal-wall
      down mastoidectomy group (53 vs. 14%). Other postoperative complications, such as
      erosion of the mastoid cavity, otorrhea, and perforation of the eardrum, occurred
      more frequently in the canal-wall-down mastoidectomy group than in the canal-wall
      up mastoidectomy group. In the late period (1991-1997), in the canal-wall-up
      mastoidectomy group, ten ears underwent one-stage surgery. Planned staged
      tympanoplasty was completed in six ears. After one-stage surgery, four of ten
      ears experienced residual cholesteatoma. Two of the recurrent ears had undergone
      planned staged tympanoplasty. As revealed by postoperative computed tomography
      (CT) images, 12 of 15 ears had aeration in the attic and antrum as well as in the
      tympanic cavity. In these cases, no attic retraction pocket formation was
      observed. CONCLUSION: Our strategy for pediatric cholesteatoma in the future is
      to use canal-wall-up mastoidectomy when possible. If aeration in the attic and
      antrum is observed by preoperative CT-scan image and no erosion in the malleus
      and incus exists, the one-stage surgery will be chosen. If no aeration is
      observed by CT-scan and/or erosion exists in the surgical findings, planned
      staged tympanoplasty will be necessary. This strategy allows a high incidence of
      aeration of the attic and antrum, and prevents the formation of the attic
      retraction pocket while enabling the early detection of residual cholesteatoma by
      means of CT.

PMID- 11240320
TI  - Histological reaction to hydroxyapatite in the middle ear of rats.
AB  - OBJECTIVE: Present study was performed to evaluate the histological response of
      rat middle ear mucosa following implantation of Apaceram granules, a synthetic
      dense hydroxyapatite [Ca10(PO4)6(OH)2], prepared from commercially available
      synthetic auditory ossicle, and to assess the precise histological response of
      the rat middle ear to implantation of Apaceram granules, by microscopic
      examination of mucosal tissue at various time points after implantation. METHODS:
      Apaceram granules were implanted in the temporal bulla of 32 rats. As control,
      sham surgery was performed in a group of ten rats. Bulla specimens were removed
      at 1, 3, 7, 14, and 30 days after surgery in the implant and control groups, and
      at 90, 180 and 300 days in the implant group. Specimens were decalcified,
      sectioned at a thickness of 6 microm, and stained with haematoxylin and eosin,
      and Mallory's azan for histological examination of mucosal tissue. RESULTS:
      Evidence of inflammatory reaction was slightly greater in the implant group than
      in controls. Lymphocyte and macrophage counts were higher in the implant group 1
      day after surgery, but decreased to similar levels by day 3, and continued to
      decrease thereafter, and few were observed in the implant group at 300 days.
      Neutrophils observed at 1 day after surgery were not evident in either group at 3
      days. Gradual fibrosis development continued in both groups over all time points
      studied. Foreign body giant cells were never observed in either group. No bony
      reaction was observed in any specimen. CONCLUSION: The results of this study
      suggest that Apaceram is biocompatible and suitable for reconstructive ear
      surgery.

PMID- 11240321
TI  - Morphological and clinical characteristics of antrochoanal polyps: comparison
      with chronic inflammation-associated polyps of the maxillary sinus.
AB  - OBJECTIVES: to compare morphological and clinical features of antrochoanal polyps
      and chronic inflammation-associated polyps of the maxillary sinus. STUDY DESIGN:
      histological and scanning electron microscopic examination of ten antrochoanal
      polyps and ten chronic inflammation-associated polyps of the maxillary sinus;
      comparison of clinical data in both groups of patients. METHODS: following
      surgical removal, the polyps were halved, the halves being processed for routine
      light microscopy (formalin fixation, paraffin embedding, HE staining) and
      scanning electron microscopy (formaldehyde/glutaraldehyde fixation, critical
      point drying, gold coating), respectively. Clinical data were retrospectively
      reviewed, tabulated and compared. RESULTS: the antrochoanal polyps differed from
      chronic inflammation-associated polyps of the maxillary sinus only in a few minor
      features; slightly longer duration of the process, lower incidence of maxillary
      ostial obstruction, higher incidence of frequent headaches, persistent nasal
      obstruction, presence of cysts in the polyp stroma, thickened basement membrane,
      lower incidence of squamous cell metaplasia, and higher proportion of migratory
      cells in nasal smears. In two cases, allergy was diagnosed but it seemed not to
      influence the polyps, which did not show morphological features typical of
      allergy-associated (eosinophilic) polyps. CONCLUSIONS: In spite of minor
      differences, antrochoanal polyps can be regarded as chronic inflammation
      associated polyps with cystic origin and peculiar localization.

PMID- 11240322
TI  - Hypophysis surgery with or without endoscopy.
AB  - OBJECTIVE: Hardy's operation with microscope has long been the standard method
      for pituitary adenoma. But a new approach via the nasal cavity using an endoscope
      has been adopted recently. In this study, the postoperative outcome as well as
      the preoperative evaluation of endoscopic hypophysectomy and non-endoscopic one
      were compared at our faculty. METHOD: We performed the non-endoscopic transnasal
      hypophysectomy on 18 patients and the endoscopic transnasal hypophysectomy on
      thirteen patients who had a pituitary lesions from February 1996 to October 1999.
      As to these patients the situations from preoperation through postoperation such
      as chief complaints, serum hormone level, final diagnosis, tumor size, as well as
      operating time or blood loss during the operation were discussed precisely. Then
      the merits and demerits of endoscopic hypophysectomy were discussed. RESULT: Five
      PRL-producing adenoma, three GH-producing adenoma, nine non-functioning adenoma,
      and two ACTH or TSH-producing adenoma were included in this discussion as
      endoscopic group. The age of non-endoscopic group are from 23 to 73 (49.4 in
      average), and they include ten males and eight females. On the other hand three
      PRL-producing adenoma, two GH-producing adenoma, two non-functioning adenoma, and
      one Rathke's cyst were included in this discussion as endoscopic group. The age
      of endoscopic group are from 19 to 73 (49.1 in average), and they include seven
      males and six females. As to non-endopscopic group the blood loss during each
      operation is 568 ml and operating time is 256 min in average. For endoscopic
      group the blood loss is 296 ml and operating time is 234 min in average.
      CONCLUSION: By microsurgery in the pituitary operation with endoscopy, the
      minimal invasive surgery becomes possible by reducing blood loss and shortening
      operating time. During the operation cooperation between neurosurgeon and ENT
      surgeon is indispensable in order to perform hypophysectomy smoothly. The
      development of optical better aids and operation instruments for endonasal
      hypophysectomy is desired in the future. The navigation system was more useful
      than X-ray fluoroscopy to obtain the detailed information.

PMID- 11240323
TI  - Helical CT scanning of laryngeal deviation.
AB  - OBJECTIVE: To evaluate helical computed tomography (CT) scanning in patients with
      laryngeal deviation. MATERIALS AND METHODS: Five patients with laryngeal
      deviation and three control subjects underwent helical CT. The laryngeal
      deviation was idiopathic in one patient and acquired in four. Three-dimensional
      (3D) images of the laryngeal cartilages and bones, 3D airway surface models, and
      sequential coronal and axial images were reconstructed for assessment. RESULTS:
      The thyroid cartilage was inclined and twisted to the right in three patients,
      inclined to the right and twisted to the left in one patient, and inclined to the
      left and twisted to the right in one patient. The infero-posterior part of the
      thyroid cartilage, and the cricoid and arytenoid cartilages were shifted to the
      left in four patients. The vocal cords were at the level of C4 approximately
      C4/C5 in two patients, C4/C5 in one, C4/C5 approximately C5 in one, and C5
      approximately C5/C6 in one. In four patients, inclination of the laryngeal cavity
      to the right may have induced left false vocal cord protrusion. The levels of the
      two false vocal cords differed in all patients. When the inclination and twisting
      were corrected on the computer, 3D images of the laryngeal cartilages of the
      patients became almost the same as those of the control subjects, except for
      slight deformity of the thyroid cartilage. The width of the right and left
      thyroid alae was measured on the computer, and was almost equal in all patients.
      3D airway surface models of the left hemilarynx resembled those of the right
      hemilarynx when the angle of view was changed on the computer. CONCLUSION: Three
      dimensional images of the laryngeal cartilages and bones, 3D airway surface
      models, and sequential coronal and axial CT scans were obtained using helical CT.
      This method allows the 3D observation of laryngeal deviation, and viewing of
      images from various directions on the computer was useful to understand the
      characteristics of laryngeal deviation.

PMID- 11240324
TI  - Laboratory data and treatment outcomes of head and neck tumor patients in the
      elderly.
AB  - OBJECTIVE: To elicit the factors influencing the choice of treatment and the
      prognosis of elderly patients, we studied the clinical and laboratory data of
      head and neck tumor patients. The patients were divided into two groups (group A:
      younger than 75, group B: 75 years of age or older) and the treatment outcomes as
      well as the features of the laboratory data were analyzed. METHODS: The clinical
      records of 1350 patients (888 males, 462 females) with head and neck tumors who
      received their initial treatment at our hospital were reviewed. The collected
      data including age, the site of the primary lesion, pre-treatment health states,
      pre-operative laboratory results were examined. According to the treatment
      policy, we grouped the patients according to whether or not they had received the
      standard therapy for the disease and then analyzed their treatment outcomes.
      RESULTS: Standard therapy was not performed in 62 (5.6%) of the 1114 patients in
      group A and in 43 (18.2%) of the 236 patients in group B. A further analysis
      performed in group B (elderly patients) revealed that standard therapy was
      performed in 193 patients, while 43 received non-standard therapy. The prognosis
      for the non-standard therapy cases was poor. The averages of the laboratory test
      findings between groups A and B were compared, but no marked differences were
      observed. However, differences were observed in the ratio of patients whose data
      were in the normal range between group A and group B. When the laboratory data
      were compared between the standard and non-standard groups of the elderly, serum
      albumin and CBC (especially hemoglobin) showed a close relationship to the
      treatment modality. CONCLUSION: The ratio of patients who did not receive
      standard therapy was high in the age group of 75 years or older. The prognosis of
      patients with head and neck tumors is therefore considered to depend on whether
      or not a patient receives the standard therapy against the disease. The pre
      treatment clinical data and the laboratory findings vary markedly among elderly
      patients 75 years of age or older. Regarding the treatment of head and neck
      tumors in the elderly, the laboratory data and clinical conditions of each
      individual patient should be checked carefully and every possible means should be
      employed in order to allow such patients to receive the standard therapy whenever
      possible.

PMID- 11240325
TI  - Metastasis of cervical esophageal carcinoma to the temporal bone--a study of the
      temporal bone histology.
AB  - A 49-year-old male developed left abducens nerve palsy as a result of metastatic
      spread of carcinoma of the cervical esophagus to Rouviere's node and infiltration
      of the petrous portion of the left temporal bone. Postmortem temporal bone
      histology revealed that cancer cells had invaded the greater superficial petrosal
      nerve (GPN), lesser superficial petrosal nerve, tensor tympani muscle (TTM) and
      the skin covering the anterior wall of the left external auditory meatus. These
      findings suggest that the carcinoma metastasized from the cervical esophagus to
      Rouviere's node and directly invaded the middle cranial fossa and then the
      temporal bone, and further infiltrated the middle ear via perineural invasion.

PMID- 11240326
TI  - A case of schwannoma on the nasal septum.
AB  - We present a case of nasal septal schwannoma. The patient was a 62-year-old
      female complaining of bilateral nasal obstruction. Anterior rhinoscopy revealed a
      smooth-surfaced mass arising from the nasal septum in both nasal cavities.
      Computed tomography scan showed a mass with enhancement in the two nasal cavities
      and the ethmoid sinuses, and this mass extended to the skull base. Lateral
      rhinotomy was performed under general anesthesia. The tumor arose from the nasal
      septum, occupied both nasal cavities, and extended to the anterior ethmoid
      sinuses. It was encapsulated and could be totally removed en bloc. Pathological
      examination of the excised specimen showed that it was an Antoni type A
      schwannoma. The tumor cells were immunoreactive for S-100 protein. The patient is
      doing well with no evidence of recurrence.

PMID- 11240327
TI  - Atlantoaxial subluxation in an adult secondary to retropharyngeal abscess.
AB  - Atlantoaxial subluxation secondary to a retropharyngeal abscess is well described
      in children, but very rare in adults. Only two adult cases have been reported in
      the literature. We present a case of severe atlantoaxial subluxation in an adult
      secondary to retropharyngeal abscess. His atlas-dens interval was very large, up
      to 10 mm in flexion. We tried external fixation with a neck collar initially, but
      for remaining instability, surgical fusion was performed. The mechanism of
      subluxation is attributed to softening of the ligament allowing greater mobility
      at the joint. The etiology of this process is speculative.

PMID- 11240328
TI  - Bilateral accessory anterior bellies of the digastric muscle and review of the
      literature.
AB  - OBJECTIVE: The aim of our paper is discussing anomalies of the anterior belly of
      the digastric muscle with presenting our case in light literature. METHODS:
      During dissection of the submental region of 26 years old Turkish female embedded
      cadaver, for this educational purpose in 2000, bilateral accessory digastric
      muscle was observed. RESULTS: The anterior and posterior bellies of the digastric
      muscle had their normal origin and course and were joined by an intermediate
      tendon, the accessory anterior bellies originated from the digastric fossa, and
      inserted to the hyoid bone, with a common fibrous band. The accessory anterior
      bellies of the digastric muscle were in the same shape and coursed parallel to
      each other. CONCLUSION: Anatomical variations of the anterior bellies of the
      digastric muscles can be easily confused with pathological conditions in CT and
      MR imaging, it is necessary to recognize that muscle variants of the digastric
      muscle occur to avoid confusion when diagnosing abnormal lesions of the floor of
      the mouth and submental region. In human body, such as these muscle variations
      have clinical significance.

PMID- 11240329
TI  - Giant lymph node hyperplasia a diagnostic dilemma in the neck.
AB  - Giant lymph node hyperplasia (GLNH) or Castleman's disease is a rare pathological
      entity commonly presenting as a solitary mediastinal tumour (unifocal variant),
      although other anatomical sites have been reported including the head and neck,
      abdomen and axilla. Though the head and neck is the second commonest site for
      this lesion, only 60 cases [1,2] have been reported in the literature. Pre
      operative diagnosis of the unifocal variant can be difficult as routine
      investigations carried out in the clinic setting are often inconclusive. A
      multicentric form of this disease with a poorer prognosis in comparison to the
      unifocal lesion has been described by Gaba et al. in 1978 [3]. We present a case
      of an unusually large, slow growing, asymptomatic, unifocal variant of this
      tumour restricted to the neck which underwent successful surgical excision. A
      review of the literature, histopathological characteristics and differential
      diagnosis is also presented.

PMID- 11240330
TI  - Basal cell adenocarcinomas of the submandibular and parotid glands recognized
      simultaneously report of a case.
AB  - Basal cell adenocarcinomas (BCAC) of the major salivary glands are rare tumors.
      We experienced a case of BCACs that were recognized simultaneously in the
      submandibular and parotid glands. The case like this has not been reported
      previously. We present the case and discuss clinicopathologically the relation
      between the both tumors. Macroscopically, there was no direct infiltration
      between the both tumors. Microscopically, neural and perineural invasion were not
      found in both tumors. Distant hematogenous metastasis to other organs was not
      found. The fact that the parotid tumor had strong necrotic change and had no
      nodal structure suggests that the metastatic node had been rapidly enlarged
      beyond the size of the normal lymph node. It is reasonable to suppose that the
      submandibular tumor is a primary lesion and the parotid tumor is a metastatic
      lymph node.

PMID- 11240331
TI  - Cardiotoxicity of 5-flourouracil: two case reports.
AB  - Cardiotoxicity is a rare but serious side effect of 5-flourouracil (5-FU). The
      cardiotoxicity incidence of 5-FU is increasing with its frequent use in
      chemotherapy protocols. To explain the mechanism of this cardiotoxicity, many
      theories have been suggested by different authors. Most commonly, coronary artery
      vasospasm and flouroacetate,a toxic metabolite of 5-FU, are considered
      responsible for the toxicity. Ischemic symptoms and signs related to 5-FU are
      observed during the late phase of the administration of the drug. The close and
      careful monitorization of all the patients, especially the ones with pre-existent
      coronary artery disease, during 5-FU infusion is mandatory. Because there is not
      a single and effective modality of treatment or prophylaxis for 5-FU
      cardiotoxicity, the patients should be selected carefully for 5-FU administration
      and 5-FU infusion should be stopped as soon as a symptom is encountered.

PMID- 11240333
TI  - Glucose infusion does not suppress increased lipolysis after abdominal surgery.
AB  - The purpose of this study was to investigate the effect of glucose infusion on
      lipid metabolism after abdominal surgery. Patients (n = 6) with non-metastasized
      colorectal carcinoma were investigated on the second day after surgery and
      healthy volunteers were studied after an overnight fast. The rates of glycerol
      appearance (R(a) glycerol), i.e., lipolysis rates, were assessed by primed
      continuous infusion of [1,1,2,3,3,-5H2]glycerol before and after 3 h of glucose
      infusion (4 mg x kg(-1) x min(-1)). Plasma concentrations of glycerol, free fatty
      acids, glucose, lactate, insulin, and glucagon were determined. Fasting R(a)
      glycerol was higher in patients than in volunteers (7.7 +/- 1.8 versus 1.9 +/-
      0.3 micromol x kg(-1) x min(-1), P < 0.05). Glucose infusion suppressed the R(a)
      glycerol in volunteers to 1.0 +/- 0.2 micromol x kg(-1) x min(-1) (P < 0.05),
      whereas lipolysis was not affected in patients. Plasma concentrations of glycerol
      and free fatty acids similarly decreased during glucose administration by 50% in
      both groups (P < 0.05). In contrast to the patients, a significant correlation (r
      = 0.78, P < 0.05) between the R(a) glycerol and plasma glycerol concentration was
      observed in normal subjects. The hyperglycemic response to glucose infusion was
      significantly more pronounced (P < 0.05) in patients (10.7 +/- 0.7 mmol/L) than
      in volunteers (7.1 +/- 0.4 mmol/L), whereas the plasma insulin increased to the
      same extent in the two groups (P < 0.001). In conclusion, lipolysis rates are
      increased after abdominal surgery and glucose administration, most likely due to
      insulin resistance, and fail to inhibit stimulated whole-body lipolysis.

PMID- 11240334
TI  - Jejunal feeding, even when instituted late, improves outcomes in patients with
      severe pancreatitis and peritonitis.
AB  - This study assessed the feasibility and effectiveness of jejunal feeding (JF)
      after surgery due to secondary peritonitis or failed conservative therapy of
      severe pancreatitis. Of 60 patients, 30 were randomly assigned to receive
      postoperative JF and the remaining 30 constituted the control group. Acute
      Physiology and Chronic Health Evaluation II, nutritional intake, systemic
      inflammatory response syndrome, and outcomes were measured. Patients in JF group
      received the daily mean of 1294.6 (362.6) kcal including 830.6 (372.7.0) kcal
      enterally, versus 472.8 (155.8) kcal daily in the control group (P < 0.0001).
      There were fewer complications in the JF patients, with no significant
      difference; length of stay in the intensive care unit and in the hospital did not
      differ. The frequency of systemic inflammatory response syndrome was similar in
      both groups, but outcomes differed. The first surgical intervention resulted in
      3.3% of relaparotomies in JF patients, caused by unresolved peritonitis, versus
      26.7% in the control subjects (P = 0.03). Recovery of bowel transit took
      significantly less time in the JF patients (mean: 54.6 h versus 76.8 h in control
      subjects, P = 0.01). JF resulted in 3.3% mortality as opposed to 23.3% in the
      control group (P = 0.05). In conclusion, JF is feasible and effective in
      postoperative treatment of patients due to secondary peritonitis or severe
      pancreatitis. Improved bowel and peritoneal function could be the main impact of
      JF.

PMID- 11240335
TI  - Plasma levels of amino acids and hypermetabolism in patients with chronic
      obstructive pulmonary disease.
AB  - Plasma levels of amino acids were measured by ion-exchange, high-pressure liquid
      chromatography in 30 ambulatory patients with chronic obstructive pulmonary
      disease (COPD; mean +/- SD: age 64 +/- 13 y and forced expiratory volume in 1 s
      [FEV1] 0.85 +/- 0.25 L) and 30 age- and sex-matched healthy control subjects with
      regard to nutritional status, resting energy expenditure (REE), and pulmonary
      function. The ratio of branched-chain amino acids to aromatic amino acids was
      significantly (P < 0.001) decreased in COPD patients and was significantly
      correlated with percentage of ideal body weight (r = 0.403, P < 0.05), percentage
      of arm-muscle circumference (r = 0.492, P < 0.01), and %FEV1 (r = 0.467, P <
      0.05). Plasma levels of alanine and cysteine were decreased, whereas levels of
      glutamine, aspartic acid, serine, and ornithine were elevated in COPD patients as
      opposed to control subjects. The ratio of resting energy expenditure to predicted
      resting energy expenditure was negatively correlated with the ratio of branched
      chain to aromatic amino acids (r = -0.716, P < 0.01), percentage of arm-muscle
      circumference (r = -0.770, P < 0.05), %FEV1 (r = -0.839, P < 0.01), and the
      maximal inspiratory pressure (r = -0.803, P < 0.001). Underweight COPD patients
      also exhibited a greater degree of hyperinflation (percentage of residual volume
      = 205 +/- 15 for underweight patients and 156 +/- 8 for normal-weight patients).
      In conclusion, a decrease in plasma levels of branched-chain amino acids in
      relation to hypermetabolism, possibly resulting from the severity of COPD and
      respiratory muscle weakness, and various disturbances in plasma amino-acid levels
      were found in underweight COPD patients.

PMID- 11240336
TI  - Refeeding procedures after 43 days of total fasting.
AB  - Refeeding syndrome encompasses fluid and electrolyte imbalances and metabolic,
      intestinal, and cardiorespiratory derangements associated with appreciable
      morbidity and mortality. Although refeeding syndrome has been well documented in
      concentration-camp subjects, and more recently during parenteral therapy of
      critically ill patients, little is known about the importance of refeeding
      syndrome during recovery from a hunger strike. Thus, we studied the response to a
      four-step dietary replenishment routine in eight hunger strikers who refused food
      for 43 d. In this retrospective, observational study, we assessed the safety and
      efficacy of the refeeding procedure and analyzed the clinical and nutritional
      course of the cohort during both starvation and refeeding, mainly on the basis of
      clinical as well as a few biochemical determinations. During starvation, average
      weight loss was about 18% and, with the exception of occasional oral vitamins and
      electrolytes, the subjects consumed only water. Available body-composition and
      biochemical profiles showed no clinically significant changes during starvation,
      but one-half of the group displayed spontaneous diarrhea at some time before
      refeeding. Stepwise nutritional replenishment lasted for 9 d, after which all
      patients tolerated a full, unrestricted diet. Only one episode of diarrhea
      occurred during this phase, and both clinical and biochemical indexes confirmed a
      favorable clinical course, without any manifestation of refeeding syndrome. In
      conclusion, we observed the following: 1) Hypophosphatemia and other
      micronutrient imbalances did not occur, nor was macronutrient intolerance
      detected. 2) Despite some episodes of diarrhea, nutritional replenishment was not
      associated with significant enteral dysfunction. 3) There was some fluid
      retention, but this was mild. 4) Acute-phase markers were abnormally elevated
      during the refeeding phase, without associated sepsis or inflammation.

PMID- 11240337
TI  - Relation of plasma leptin concentrations to sex, body fat, dietary intake, and
      peak oxygen uptake in young adult women and men.
AB  - The purpose of this study was to examine the relation of leptin to metabolic and
      dietary factors in college-age adults. Young adult women and men (n = 32) were
      recruited and underwent testing for measurement of body mass index, body
      composition, peak oxygen consumption (VO2peak), dietary intake, and plasma levels
      of leptin and insulin. Ln leptin was significantly greater for women than for men
      (2.1 versus 1.2 ng/mL, respectively). This difference remained significant even
      after adjusting ln leptin for fat mass and fat-free mass as covariates in
      separate analyses. VO2peak was higher for men than for women and this remained
      significant after adjustment for differences in fat-free mass and total body
      mass. Significant correlations were found between ln leptin and indicators of fat
      mass in women and men, with higher correlations for similar variables observed in
      men (r = 0.548, 0.674, and 0.732 for body mass index, percentage of body fat, and
      fat mass [kg] for women, respectively, and r = 0.740, 0.888, 0.858 for body mass
      index, percentage of body fat, and fat mass [kg] for men, respectively). Ln
      leptin showed a significant inverse relationship with VO2peak (r = -0.751) in men
      only. After adjusting ln leptin for body fat mass using partial correlations, ln
      leptin was not significantly associated with any of the measured variables.
      Alternatively, after normalization of ln leptin using fat mass as the divisor, a
      less adequate statistical analysis method, men showed statistical significant
      correlations between ln leptin and dietary intake and VO2peak. Although plasma
      leptin values were higher in women, stronger associations were evident for men
      than for women between leptin and metabolic and dietary factors.

PMID- 11240338
TI  - Parenteral supplementation with a fish-oil emulsion prolongs survival and
      improves rat lymphocyte function during sepsis.
AB  - Nutritional intervention with omega-3 fatty acids during trauma and infection has
      been shown to improve the clinical outcome of patients and the survival rate in
      laboratory animals. This study evaluated the effects of parenteral administration
      of lipid emulsions containing fish oil (FO) or soybean oil (SBO) on survival and
      T-lymphocyte response during sepsis. Male Sprague-Dawley rats (250-275 g) were
      prepared for parenteral feeding 4 d before inducing sepsis by cecal ligation and
      puncture (CLP). Standard resuscitation was provided with normal saline. Thirty
      minutes after completing CLP, sham control or CLP rats were infused continuously
      with saline or a parenteral diet containing SBO or a 1:1 FO:SBO emulsion. The
      survival rate was significantly improved in rats receiving the FO-supplemented
      diet, with 50% alive by 120 h in comparison with the saline-infused, chow-fed
      rats (0% alive by 120 h) or the SBO-fed rats (12% alive at 120 h). The T
      lymphocyte response was evaluated at 24 h after CLP. Sepsis led to a decline in
      lymphocyte proliferation in rats infused with saline or the SBO emulsion, which
      was associated with a greater release of splenocyte interleukin-10, transforming
      growth factor-beta and prostaglandin E2. Administering the 1:1 FO:SBO parenteral
      diet during sepsis improved the survival rate and prevented the sepsis-induced
      suppression of lymphocyte proliferation and interleukin-2 release. The FO effect
      on lymphocyte function was associated with decreased splenocyte release of
      transforming growth factor-beta and prostaglandin E2.

PMID- 11240339
TI  - Long-term optional ingestion of corn oil induces excessive caloric intake and
      obesity in mice.
AB  - Corn oil is well tolerated by mice but tolerance may decrease with excessive
      ingestion. In the present study, we compared the effects of optional ingestion of
      excessive corn oil with ingestion of water (control) or a 20% sucrose solution in
      mice. During the entire study, mice consistently ingested 100% corn oil and
      incrementally ingested 20% sucrose. Food intake in the corn-oil group was
      approximately constant but that in the sucrose group was slightly decreased. Body
      weight gains in the corn-oil group were higher than those in the control and
      sucrose groups. At the end of the study, hepatic hypertrophy and fatty liver were
      present, especially in the corn-oil group, and the visceral fat of mice fed corn
      oil increased significantly compared with the other two groups. These results
      suggest that mice, when given a choice, will continue to overeat corn oil over
      the long term, inducing excessive caloric intake and obesity.

PMID- 11240340
TI  - Improving outcome of pressure ulcers with nutritional interventions: a review of
      the evidence.
AB  - Pressure ulcers and malnutrition frequently co-exist in frail patients.
      Nutritional parameters have been correlated with development and with healing in
      chronic pressure ulcers, leading to suggestions that improving nutritional status
      can prevent or treat pressure ulcers. Despite a strong association, a causal
      relationship of poor nutritional status to development of pressure ulcers has not
      been established. Support for a causal relationship would include evidence that
      nutritional interventions improve general nutritional status, acute wound
      healing, or chronic wound healing. The data suggesting that nutritional
      intervention can improve clinical outcome are limited. No study has demonstrated
      that improvement in nutritional status can prevent pressure ulcers. There is at
      least suggestive evidence that improvement in nutritional status can improve
      outcome in pressure ulcer healing.

PMID- 11240341
TI  - Prevention of chemically induced diabetes mellitus in experimental animals by
      polyunsaturated fatty acids.
AB  - Previous studies showed that essential fatty-acid deficiency, conjugated linoleic
      acid, and a peroxisome proliferator-activated receptor-gamma binding agent such
      as troglitazone can prevent the development of diabetes mellitus in experimental
      animals. In the present study, we observed that oral supplementation with oils
      rich in omega-3 eicosapentaenoic acid and docosahexaenoic acid and omega-6 gamma
      linolenic acid and arachidonic acid could protect the animals against alloxan
      induced diabetes mellitus. These oils rich in omega-3 and omega-6 fatty acids not
      only significantly attenuated chemical-induced diabetes mellitus but also
      restored the antioxidant status to normal range. Changes in the concentrations of
      different fatty acids shown by the phospholipid fractions of plasma, liver, and
      muscle tissues that occurred as a result of alloxan-induced diabetes mellitus
      also reverted to normal in these animals. Based on these results and the known
      mechanisms of alloxan, we suggest that omega-3 and omega-6 long-chain fatty acids
      can prevent chemically induced diabetes mellitus by enhancing the antioxidant
      status and suppressing production of cytokines.

PMID- 11240342
TI  - Abnormal liver function tests in a patient fed with total parenteral nutrition
      and treated with octreotide.
AB  - Octreotide is a long-acting analog of somatostatin, a hypothalamic release
      inhibiting hormone. It is sometimes used therapeutically to relieve symptoms
      associated with acromegaly and gastroenteropancreatic endocrine tumors. It has
      also been used in the treatment of short-bowel syndrome and gastrointestinal and
      biliary fistulae. We report a patient with biliary leakage due to Marizzi's
      syndrome treated with total parenteral nutrition and octreotide who developed
      abnormal liver function tests that improved when the two treatments were stopped.
      We also review the literature regarding abnormal liver function tests in patients
      on total parenteral nutrition.

PMID- 11240343
TI  - Nutritional intervention trials for preventing and treating pressure ulcer.

PMID- 11240344
TI  - Jejunal feeding in severe pancreatitis and peritonitis.

PMID- 11240345
TI  - Nutritional care in renal disease patients.

PMID- 11240346
TI  - More good news about fish oil.

PMID- 11240347
TI  - Reactive oxygen species in human health and disease.

PMID- 11240348
TI  - The changing epidemiologic scene: malnutrition versus chronic diseases in India.

PMID- 11240349
TI  - Nutrition support on ITU--is it worth it?

PMID- 11240350
TI  - How to explain an interaction.
AB  - In this column, I have considered some simple tabular and graphical techniques
      that are helpful in explaining the substantive meaning of an interaction. When
      both of the explanatory variables are discrete, these techniques are easy to
      apply and provide both qualitative and quantitative interpretations of the
      interaction. As noted earlier, the more challenging case is one in which one or
      more of the explanatory variables are quantitative. One simple proposal is to
      construct two "reference levels" for each of the quantitative explanatory
      variables Then, given this set of reference levels, the explanation of the
      interaction can proceed along the same lines as for the case in which both
      explanatory variables are discrete. However, some care must be taken in the
      choice of reference levels.

PMID- 11240351
TI  - Balancing the quality cycle: tackling the measurement-improvement gap in health
      care. Part I.

PMID- 11240352
TI  - Case study of patients helping patients program.

PMID- 11240353
TI  - Compromised dental function and nutrition.

PMID- 11240354
TI  - Comparison of inverse dynamics calculated by two- and three-dimensional models
      during walking.
AB  - The purpose of the study was to compare joint moments calculated by a two- (2D)
      and a three-dimensional (3D) inverse dynamics model to examine how the different
      approaches influenced the joint moment profiles. Fifteen healthy male subjects
      participated in the study. A five-camera video system recorded the subjects as
      they walked across two force plates. The subjects were invited to approach a
      walking speed of 4.5 km/h. The ankle, knee and hip joint moments in the sagittal
      plane were calculated by 2D and 3D inverse dynamics analysis and compared.
      Despite the uniform walking speed (4.53 km/h) and similar footwear, relatively
      large inter-individual variations were found in the joint moment patterns during
      the stance phase. The differences between individuals were present in both the 2D
      and 3D analysis. For the entire sample of subjects the overall time course
      pattern of the ankle, knee and hip joint moments was almost identical in 2D and
      3D. However, statistically significant differences were observed in the magnitude
      of the moments, which could be explained by differences in the joint centre
      location and joint axes used in the two approaches. In conclusion, there were
      differences between the magnitude of the joint moments calculated by 2D and 3D
      inverse dynamics but the inter-individual variation was not affected by the
      different models. The simpler 2D model seems therefore appropriate for human gait
      analysis. However, comparisons of gait data from different studies are
      problematic if the calculations are based on different approaches. A future
      perspective for solving this problem could be to introduce a standard proposal
      for human gait analysis.

PMID- 11240355
TI  - Hip locomotion mechanisms in cerebral palsy crouch gait.
AB  - The purpose of this study was to evaluate three defined locomotion patterns in
      cerebral palsy gait using computerised gait analysis. Ambulant diplegic children
      who had no previous surgery were included in the study and were divided into two
      groups: one group consisted of children having a crouch gait, and the other group
      did not have the crouch pattern of gait. An age-matched group of normal children
      served as the control group. Locomotion patterns studied were the hip hike,
      propulsive function of the hip extensors, and pseudo-adduction. A statistical
      analysis was performed between the groups, using defined parameters. The
      mechanism of hip hike was not utilised by any of the groups. Both groups of
      diplegic children showed power generation at the hip beginning in the first
      double support phase of the gait cycle and continuing in the first half of single
      limb support, while in the normals this was only in the first half of single limb
      support. Both the groups of diplegic children showed significantly more internal
      rotation in the first half of stance as compared to the group of normal children;
      the degree of hip adduction was the same in all the groups. Thus diplegic
      children had pseudo-adduction.

PMID- 11240356
TI  - Influence of steep gradient supporting walls in rock climbing: biomechanical
      analysis.
AB  - This study analyses the reaction forces and variations of rock climbing in
      vertical and overhanging positions. Subjects voluntarily released their right
      foot and regained equilibrium. In the overhanging position the quadrupedal state
      was characterised by a significant involvement of the arms to prevent fall.
      Moreover, the horizontal forces applied to the holds were less important, which
      suggests that equilibrium was easier to maintain than in the vertical position.
      The tripedal state was characterised by less extensive contralateral supporting
      force transfer on the remaining holds in the overhanging position, which
      reinforces safety.

PMID- 11240357
TI  - The control of body orientation and center of mass location under asymmetrical
      loading.
AB  - This study examined how whole body center of mass (COM) in the medial-lateral
      direction and spatial orientation of body segments changed during quiet stance
      when a weight was loaded on asymmetrically on the right side of the pelvis. The
      load corresponded to 10 and 30% of body weight (BW) of each individual subject,
      and the stance width was varied from narrow (7.6 cm) to normal (20 cm) and to
      wide (33 cm). A total of 10 healthy young subjects (18-30 years of age)
      participated in the study. The results indicated that the COM location was
      significantly shifted towards the loaded side (about 1.2 cm with a 10% BW load
      and 3 cm with a 30% BW load). In addition, COM was closer to the center with a
      narrow stance (0.38 cm to the right of the center) than both normal and wide
      stance (about 1 cm to the right). However, the COM shifts for all test conditions
      were smaller (<50%) than that of the theoretically predicted values. The smaller
      shift in COM position appeared to be mostly due to the change in spatial
      orientation of the pelvis and lower extremity (about 2.5 degrees change with a
      10% BW load, and 4.5 degrees change with a 30% BW load), while maintaining the
      upper body orientation relatively unchanged (less than 2 degrees with a 30% BW
      load). This strategy may allow increased stability of the upright stance with
      minimal amount of muscle activation.

PMID- 11240358
TI  - A review of analytical techniques for gait data. Part 2: neural network and
      wavelet methods.
AB  - Multivariate gait data have traditionally been challenging to analyze. Part 1 of
      this review explored applications of fuzzy, multivariate statistical and fractal
      methods to gait data analysis. Part 2 extends this critical review to the
      applications of artificial neural networks and wavelets to gait data analysis.
      The review concludes with a practical guide to the selection of alternative gait
      data analysis methods. Neural networks are found to be the most prevalent non
      traditional methodology for gait data analysis in the last 10 years.
      Interpretation of multiple gait signal interactions and quantitative comparisons
      of gait waveforms are identified as important data analysis topics in need of
      further research.

PMID- 11240366
TI  - Session 4. performance and potential of clinical movement analysis laboratories.

PMID- 11240367
TI  - Thermal hysteresis proteins.
AB  - Extreme environments present a wealth of biochemical adaptations. Thermal
      hysteresis proteins (THPs) have been found in vertebrates, invertebrates, plants,
      bacteria and fungi and are able to depress the freezing point of water (in the
      presence of ice crystals) in a non-colligative manner by binding to the surface
      of nascent ice crystals. The THPs comprise a disparate group of proteins with a
      variety of tertiary structures and often no common sequence similarities or
      structural motifs. Different THPs bind to different faces of the ice crystal, and
      no single mechanism has been proposed to account for THP ice binding affinity and
      specificity. Experimentally THPs have been used in the cryopreservation of
      tissues and cells and to induce cold tolerance in freeze susceptible organisms.
      THPs represent a remarkable example of parallel and convergent evolution with
      different proteins being adapted for an anti-freeze role.

PMID- 11240368
TI  - Age-dependent variation in contractility of adult cardiac myocytes.
AB  - This study was designed to examine the influence of the age of adults on the
      contractile characteristics of the myocardium and to ascertain whether the age
      dependent variation is related to variation in sarcolemmal calcium channels.
      Cardiomyocytes were isolated from 2, 6 and 12-month-old, male Sprague-Dawley rats
      and the extent and velocity of contraction were recorded as a function of change
      in cell length. Age dependent increase in cell length and sarcomere length was
      significant (P<0.05). Extent of contraction increased with age and the velocities
      of contraction and relaxation normalized to total contraction decreased with age
      (P<0.05). Sensitivity to the L-type channel antagonist (verapamil, 1 microM) and
      the T-type channel antagonist (nickel chloride, 40 microM) was significant in 6
      and 12-month-old animals. This differential response to calcium channel
      antagonists suggests that the age-dependent variation in contractility may be
      mediated by the variation in the distribution/function of sarcolemmal calcium
      channels.

PMID- 11240369
TI  - Cloning and cDNA sequence analysis of Lys(49) and Asp(49) basic phospholipase
      A(2) myotoxin isoforms from Bothrops asper.
AB  - Snake venom myotoxic phospholipases A(2) contribute to much of the tissue damage
      observed during envenomation by Bothrops asper, the major cause of snake bites in
      Central America. Several myotoxic PLA(2)s have been identified, but their
      mechanism of myotoxicity is still unclear. To aid in the molecular
      characterization of these venom toxins, the complete open reading frames encoding
      two Lys(49) and one Asp(49) basic PLA(2) myotoxins from the Central American
      snake B. asper (terciopelo) were obtained by cDNA cloning from venom gland poly
      adenylated RNA. The amino acid sequence deduced from the myotoxins II and III
      open reading frames corresponded in each case to one of the reported amino acid
      sequence isoforms. The sequence of a new myotoxin IV-like sequence (MT-IVa)
      contains conservative Val-->Leu(18) and Ala-->Val(23) substitutions when compared
      with the reported N-terminus of the native myotoxin IV, suggesting minor isoform
      variations among specimens of a single species. Sequence alignment studies
      indicated significant (>75% sequence identity) identities with other crotalid
      venom Lys(49) PLA(2)s, particularly bothropstoxin I/Ia isoforms of B. jararacussu
      and myotoxin II of B. asper.

PMID- 11240370
TI  - Overexpressing eukaryotic translation initiation factor 4E stimulates bovine
      mammary epithelial cell proliferation.
AB  - BACKGROUND AND AIMS: The eukaryotic translation initiation factor 4E regulates
      the proliferation of many cell types. In the present study, the effect of its
      overexpression on the growth of an immortalized bovine mammary epithelial cell
      line, MAC-T, has been investigated. Since involvement of cyclin D1 in growth
      regulation of other cell types has been suggested previously, the differences in
      cyclin D1 expression among the 4E-overexpressing and parental cells were also
      investigated. METHODS: The cDNA of mouse eukaryotic translation initiation factor
      4E coding region (either wild-type or mutant, where Trp-56 was mutated to Ala)
      was transfected into MAC-T cells, and its protein expression was detected by
      Western blot analysis. Growth rates and saturation densities were calculated
      based on the cell counting data at desired time points. KEY RESULTS: The cells
      overexpressing wild-type 4E displayed higher growth rates and saturation
      densities compared to the parental cells (P<0.05), whereas cells expressing
      mutant 4E showed lower growth rates and saturation densities than the parental
      controls (P<0.05). The amounts of cyclin D1 mRNA and protein were higher in the
      wild-type transfectants than in the parental controls, whereas the mutant
      transfectants contained lower amounts of cyclin D1 mRNA and protein compared to
      the parental cells. CONCLUSION: Our results suggest that overexpression of
      eukaryotic translation initiation factor 4E leads to increased cyclin D1
      expression at the transcriptional level, which consequently stimulates the
      proliferation of MAC-T cells.

PMID- 11240371
TI  - Oxidases and reductases are involved in metronidazole sensitivity in Helicobacter
      pylori.
AB  - Helicobacter pylori is a contributing factor to the development of gastric and
      duodenal ulcers and some gastric cancers. Some therapeutic regimes comprise of a
      number of components, one of which is the antimicrobial metronidazole. A problem
      with these therapies is the increasing prevalence of metronidazole-resistant
      (MtrR) H. pylori strains. Several resistance mechanisms have been proposed, and
      this study addresses the 'scavenging of oxygen' hypothesis. Spectrophotometric
      assays of cytosolic fractions indicated that metronidazole-sensitive (MtrS) H.
      pylori isolates had 2.6-fold greater nicotinamide adenine dinucleotide (NADH)
      oxidase activity, 34-fold greater NADH nitroreductase activity, and eightfold
      greater nicotinamide adenine dinucleotide phosphate (NADPH) nitroreductase
      activity than cytosolic fractions from matched MtrR strains. Electrophoresis of
      cytosolic fractions in non-denaturing gels showed up to 10 protein bands when
      stained with Coomassie blue. Activity staining of non-denaturing, non-reducing
      polyacrylamide gels detected NAD(P)H oxidase, disulphide reductase, tetrazolium
      reductase and nitroreductase activities in the protein bands. Oxidase and
      reductase activities observed in a band from MtrS strains were absent in the
      corresponding band from MtrR strains. This band comprised at least 13 proteins,
      and the major constituent was identified as an alkyl hydroperoxide reductase AhpC
      subunit. The absence of oxidase and reductase activities in the band from MtrR
      strains indicated a correlation between the activity of the proteins in this band
      and the metronidazole-sensitive phenotype.

PMID- 11240372
TI  - The optical interconversion of the P-450 and P-420 forms of neuronal nitric oxide
      synthase: effects of sodium cholate, mercury chloride and urea.
AB  - We investigated whether or not neuronal nitric oxide synthase (nNOS) (EC
      1.14.13.39) was converted to the P-420 form on exposure to sodium cholate,
      mercury chloride or urea, and the reconversion of the P-420 to the P-450 form.
      Sodium cholate and mercury chloride induced the conversion of nNOS from the P-450
      to the P-420 form in concentration- and incubation time-dependent manners, and
      the nNOS activity decreased. In the presence of glycerol, L-arginine and/or
      tetrahydrobiopterin, the sodium cholate-treated P-420 form could be reconverted
      to the P-450 form under constant experimental conditions, and the nNOS activity
      could also be restored. The mercury chloride-treated P-420 form of nNOS could be
      reconverted to the P-450 form on incubation with reduced glutathione (GSH) or L
      cysteine, and the nNOS activity was recovered. However, no reconversion of the
      mercury chloride-treated P-420 form to the P-450 form was observed in the
      presence of glycerol, L-arginine, or tetrahydrobiopterin. Urea (4.0 M)
      dissociated nNOS into its subunits, but nNOS remained in the P-450 form. The nNOS
      monomer was more susceptible to sodium cholate. After removing the urea by
      dialysis, and supplementation of the nNOS solution with glycerol, L-arginine or
      BH(4), the P-420 was reconverted to the P-450 form, and the reassociation of nNOS
      monomers was also observed. These results suggested that nNOS was more stable as
      to exposure to sodium cholate, mercury chloride or urea in comparison to
      microsomal cytochrome P-450, which may be due to the different heme environment
      and protein structure.

PMID- 11240373
TI  - Parasitism enhances the induction of glucogenesis by the insect, Manduca sexta L.
AB  - Metabolic alterations that accompany parasitism of invertebrate animals can play
      an important role in parasite development. Employing 13C NMR, this study examined
      pyruvate cycling from (2-(13)C)pyruvate in the lepidopteran insect Manduca sexta,
      and the effects of parasitism by the hymenopteran Cotesia congregata on the
      gluconeogenic formation of trehalose, the haemolymph or blood sugar of insects.
      Larvae were maintained on a semi-synthetic sucrose-free diet, or on the same diet
      with sucrose at 8.5 g/l. Pyruvate cycling was evident from the 13C enrichment in
      C3 of alanine, derived following carboxylation to oxaloacetate, and was similar
      in parasitized and normal insects regardless of diet. Trehalose was formed
      following de novo synthesis of glucose, and net synthesis was estimated from the
      13C distribution in trehalose and alanine. The 13C-enrichment ratio [2trehalose
      C6/alanine C3] is an indicator of the level of gluconeogenesis relative to
      glycolysis, both enrichments were derived from (2-(13)C)pyruvate in the same
      manner. The ratio was greater than unity in all insects, regardless of diet, but
      was significantly greater in parasitized larvae, demonstrating an enhanced level
      of gluconeogenesis. This was confirmed by analysis of the 13C distribution in
      trehalose and glutamine derived from (3-(13)C)alanine. Despite enhanced de novo
      trehalose formation in parasitized insects, the haemolymph sugar level was
      similar to that of normal larvae. Because haemolymph trehalose regulates dietary
      carbohydrate intake, but not gluconeogenesis, the results suggest that
      accelerated induction of gluconeogenesis is an adaptive response to parasitism
      that provides increased carbohydrate for parasite growth and simultaneously
      maintains nutrient intake.

PMID- 11240374
TI  - Supercoiling unwinds two-micrometer plasmid yeast DNA at the origin of
      replication.
AB  - All studied origins of replication of DNA in Saccharomyces cerevisiae contain DNA
      unwinding elements. The introduction of unrestrained negative supercoiling leads
      to melting of the two DNA strands in DNA unwinding elements. To understand the
      mechanism of DNA replication it is important to know whether the most unstable
      region of DNA coincides with the origin of replication. Two-micrometer plasmid
      DNA from S. cerevisiae inserted in pBR322 was investigated by cleaving with snake
      venom phosphodiesterase. Its single-strand endonucleolytic activity allows
      cutting of negatively supercoiled DNA in the DNA unwinding elements. The sites of
      the venom phosphodiesterase hydrolysis were mapped by restriction enzymes. This
      study shows that the unwinding of the two-micrometers plasmid DNA of S.
      cerevisiae takes place only in the origin of replication as a result of
      unrestrained negative supercoiling.

PMID- 11240375
TI  - Kinetic analysis of enzyme systems with suicide substrate in the presence of a
      reversible competitive inhibitor, tested by simulated progress curves.
AB  - The use of suicide substrates remains a very important and useful method in
      enzymology for studying enzyme mechanisms and designing potential drugs. Suicide
      substrates act as modified substrates for the target enzymes and bind to the
      active site. Therefore the presence of a competitive reversible inhibitor
      decreases the rate of substrate-induced inactivation and protects the enzyme from
      this inactivation. This lowering on the inactivation rate has evident
      physiological advantages, since it allows the easy acquisition of experimental
      data and facilitates kinetic data analysis by providing another variable
      (inhibitor concentration). However despite the importance of the simultaneous
      action of a suicide substrate and a competitive reversible inhibition, to date no
      corresponding kinetic analysis has been carried out. Therefore we present a
      general kinetic analysis of a Michaelis-Menten reaction mechanism with double
      inhibition caused by both, a suicide substrate and a competitive reversible
      inhibitor. We assume rapid equilibrium of the reversible reaction steps involved,
      while the time course equations for the reaction product have been derived with
      the assumption of a limiting enzyme. The goodness of the analytical solutions has
      been tested by comparison with the simulated curves obtained by numerical
      integration. A kinetic data analysis to determine the corresponding kinetic
      parameters from the time progress curve of the product is suggested. In
      conclusion, we present a complete kinetic analysis of an enzyme reaction
      mechanism as described above in an attempt to fill a gap in the theoretical
      treatment of this type of system.

PMID- 11240376
TI  - Deoxycholate induces DNA damage and apoptosis in human colon epithelial cells
      expressing either mutant or wild-type p53.
AB  - Diets rich in fat result in higher concentrations of secondary bile acids or
      their salts in the colon, which may adversely affect cells of the colonic
      epithelium. Because secondary bile acids are thought to be genotoxic, exposing
      colon epithelial cells to secondary bile acids may induce DNA damage that might
      lead to apoptosis. The requirement for the p53 tumor suppressor gene in such
      events is unknown. In particular, the effects of secondary bile acids on colon
      epithelial cells having different p53 tumor suppressor gene status have not been
      examined. Therefore, HCT-116 and HCT-15 human colon adenocarcinoma cells, which
      express the wild-type and mutant p53 genes, respectively, were exposed to
      physiological concentrations of deoxycholate. The cells were then analyzed for
      evidence of DNA damage and apoptosis. After 2 h of incubation with 300 microM
      deoxycholate, both cell lines had greater levels of single-strand breaks in DNA
      as assessed by the comet assay. After 6 h of exposure to deoxycholate, HCT-116
      and HCT-15 cells showed morphological signs of apoptosis, i.e., membrane blebbing
      and the presence of apoptotic bodies. Chromatin condensation and fragmentation
      were also seen after staining DNA with 4',6-diamidino-2-phenylindole. Other
      apoptotic assays revealed greater binding of annexin V-fluorescein
      isothiocyanate, as well as greater post-enzymatic labeling with dUTP-fluorescein
      isothiocyanate, by both cell lines exposed to deoxycholate. These data suggest
      that deoxycholate caused DNA damage in colon epithelial cells that was sufficient
      to trigger apoptosis in a p53-independent manner.

PMID- 11240378
TI  - Application of the Vienna Classification for Crohn's disease to a single
      clinician database of 877 patients.
AB  - An international working party at the World Congress of Gastroenterology held in
      Vienna, Austria from September 6 to 11, 1998 defined a classification for Crohn's
      disease based on patient age at diagnosis (eg, less than 40 years of age, 40
      years of age or older), disease location (eg, terminal ileum, colon, ileocolon or
      upper gastrointestinal tract) and behaviour (eg, stricturing, penetrating).
      Disease location in the upper gastrointestinal tract was defined by disease being
      present proximal to the terminal ileum, regardless of terminal ileal or colon
      involvement. A 20-year, single clinician database of 877 patients from a
      university campus hospital was used, and comprised 492 women (56.1%) and 385 men
      (43.9%). Of these patients, 740 (84.4%) were diagnosed before age 40 years and
      137 (15.6%) were diagnosed by 40 years of age or older. Disease was located in
      the terminal ileum alone in 222 patients (25.3%), colon alone in 238 patients
      (27.2%) and ileocolon in 304 patients (34.6%). Another 113 patients (13.1%) had
      disease in the upper gastrointestinal tract, usually with disease also in the
      terminal ileum (23 patients), colon (12 patients) or ileocolon (71 patients).
      Only seven of 877 patients had disease located in the upper gastrointestinal
      tract alone with no distal disease. Disease behaviour could be classified as
      nonstricturing and nonpenetrating in 256 patients (29.2%), stricturing in 294
      patients (33.6%) and penetrating in 327 patients (37.2%). Of the 877 patients
      with Crohn's disease, 837 were white, 38 were Asian and two were black. In this
      tertiary care setting of a single clinician practice in a Canadian teaching
      hospital at the University of British Columbia, Crohn's disease predominantly
      affects women, and young adults with a high rate of stricturing and penetrating
      complications.

PMID- 11240379
TI  - Splanchnic and systemic hemodynamic derangement in decompensated cirrhosis.
AB  - Patients with cirrhosis and portal hypertension exhibit characteristic
      hemodynamic changes with hyperkinetic systemic circulation, abnormal distribution
      of blood volume and neurohumoral dysregulation. Their plasma and noncentral blood
      volumes are increased. Splanchnic vasodilation is of pathogenic significance to
      the low systemic vascular resistance and abnormal volume distribution of blood,
      which are important elements in the development of the concomitant cardiac
      dysfunction, recently termed 'cirrhotic cardiomyopathy'. Systolic and diastolic
      functions are impaired with direct relation to the degree of liver dysfunction.
      Significant pathophysiological mechanisms are reduced beta-adrenergic receptor
      signal transduction, defective cardiac excitation-contraction coupling and
      conductance abnormalities. Vasodilators such as nitric oxide and calcitonin gene
      related peptide are among the candidates in vasodilation and increased arterial
      compliance. Reflex-induced, enhanced sympathetic nervous system activity,
      activation of the renin-angiotensin aldosterone system, and elevated circulation
      vasopressin and endothelin-1 are implicated in hemodynamic counter-regulation in
      cirrhosis. Recent research has focused on the assertion that the hemodynamic and
      neurohumoral abnormalities in cirrhosis are part of a general cardiovascular
      dysfunction, influencing the course of the disease with the reduction of organ
      function, with sodium and water retention as the outcome. These aspects are
      relevant to therapy.

PMID- 11240380
TI  - Autoimmune hepatitis: Clinical manifestations and diagnostic criteria.
AB  - In 1998, the International Autoimmune Hepatitis Group--a panel of 40
      hepatologists and hepatopathologists from 17 countries who have a particular
      interest in autoimmune hepatitis (AIH)--undertook a review, in light of
      subsequent experience, of the descriptive criteria and diagnostic scoring system
      that it had proposed in 1993 for the diagnosis of AIH. This review (published in
      1999) noted that the original descriptive criteria appeared to be quite robust
      and required only relatively minor modifications to bring them up to date with
      developments and experience in diagnostic modalities for liver disease in
      general. Analysis of published data on the application of the original criteria
      in nearly 1000 patients revealed that the diagnostic scoring system had an
      overall diagnostic accuracy of 89.8%, with a sensitivity of 98.0%. Specificity
      for excluding definite AIH in patients with chronic viral hepatitis and
      circulating autoantibodies or patients with overlapping cholestatic syndromes was
      98% to 100%, but specificity for excluding probable AIH in these disorders ranged
      from only 60% to 80%. Modifications, including adjustments to the weightings
      against biochemical and histological cholestatic features, have been made to the
      scoring system to improve its specificity.

PMID- 11240381
TI  - Crohn's disease of the esophagus: Three cases and a literature review.
AB  - Three cases of esophageal Crohn's disease (CD) are described, each with dysphagia
      and/or odynophagia caused by esophageal ulceration. All three patients had
      associated ileocolitis. One patient followed for a prolonged period responded to
      treatment with sulfasalazine and prednisone. A computer search back to 1967
      produced 72 additional cases of esophageal CD. Among these 75 patients (total),
      who were, on average, 34 years old, esophageal disease was the presenting disease
      symptom in 41 patients (55%). The diagnosis was difficult in 13 patients, in whom
      no distal bowel disease was detected at the time of initial esophageal
      presentation. The most common presentation was dysphagia associated with aphthous
      or deeper ulcerations (52 patients). In 11 of these patients, oral aphthous
      ulcerations were also present. Esophageal stenosis or fistulas to surrounding
      structures were present in 27 patients and led to surgery in 17 patients. Most of
      the unfavourable outcomes were in this group of 27 patients with esophageal
      complications, including five deaths. Fourteen additional patients required
      surgery for CD of other areas. Responses of uncomplicated ulcerative disease of
      the esophagus tended to be favourable if the medical regimen included prednisone.
      Clinical patterns of esophageal CD were divided into three categories:
      ulcerative, stenosing and asymptomatic (acute disease in children).

PMID- 11240382
TI  - Elevated carbohydrate antigen 19-9 in patients with true (epithelial) splenic
      cysts--Rare or undiscovered?
AB  - Carbohydrate antigen 19-9 is a well known marker for pancreatic adenocarcinoma.
      However, its limitation is its nonspecificity, because elevated levels may be
      encountered in other gastrointestinal disorders, both benign and malignant. The
      following case is a patient with a true (epithelial) splenic cyst with elevated
      serum levels of carbohydrate antigen 19-9.

PMID- 11240383
TI  - A case of chronic pancreatic insufficiency due to valproic acid in a child.
AB  - A 14-year-old child treated with valproic acid over several years for a seizure
      disorder developed abdominal pain with radiological evidence of acute
      pancreatitis. The association with valproic acid was not recognized, and the
      child continued to take the drug. The patient eventually developed steatorrhea
      and weight loss that improved with pancreatic enzyme replacement. Radiological
      evaluation showed an atrophic pancreas. Without evidence of other etiological
      factors, valproic acid by itself appeared to be the cause of chronic pancreatitis
      with exocrine pancreatic insufficiency in this patient.

PMID- 11240384
TI  - Pouchitis-associated iritis (uveitis) following total proctocolectomy and ileal
      pouch-to-anal anastomosis in ulcerative colitis.
AB  - A 26-year-old woman with ulcerative colitis treated with a proctocolectomy and
      ileal pouch-to-anal anastomosis developed an erosive and ulcerative pouchitis.
      Although no ophthalmological manifestations were present before the staged
      surgical procedures, iritis developed after appearance of the pouchitis. Both
      conditions subsequently resolved with oral corticosteroids and metronidazole.

PMID- 11240385
TI  - Multiple focal nodular hyperplasia and steatosis: Atypical imaging
      characteristics.
AB  - Focal nodular hyperplasia is a rare, benign condition of the liver. A 28-year-old
      woman with malignant melanoma, mild liver enzyme abnormalities, steatohepatitis
      and newly documented hepatic lesions is described. Ultrasound, computed
      tomography and magnetic resonance imaging suggested only areas of focal fatty
      sparing but could not eliminate the concern for metastases. A (99m)technetium
      labelled sulphur colloid scan, however, revealed areas of increased uptake
      consistent with multiple focal nodular hyperplasia. This diagnosis was ultimately
      confirmed with a liver biopsy. The investigation of a patient with a malignancy
      and expanding hepatic lesions is challenging. This case illustrates the
      usefulness of the (99m)technetium-labelled sulphur colloid scan in the evaluation
      of patients with hepatic lesions.

PMID- 11240386
TI  - Lactoferrin and its biological functions.
AB  - Lactoferrin, a component of mammalian milk, is a member of the transferrin
      family. These glycoproteins transfer Fe(3+) ions. Lactoferrin is a unique
      polyfunctional protein that influences cell proliferation and differentiation. It
      can regulate granulopoiesis and DNA synthesis in some cells. Lactoferrin inhibits
      prostaglandin synthesis in human milk macrophages and activates the nonspecific
      immune response by stimulating phagocytosis and complement. It can interact with
      DNA, RNA, proteins, polysaccharides, heparin-like polyanions, etc.; in some of
      its effects, lactoferrin is found in complexes with ligands. It was recently
      demonstrated that lactoferrin also possesses ribonuclease activity and is a
      transcription factor. The list of known biological activities of lactoferrin is
      constantly increasing. This review analyzes possible mechanisms of its
      polyfunctionality.

PMID- 11240387
TI  - Thrombin as a regulator of inflammation and reparative processes in tissues.
AB  - Activation of blood coagulation and thrombin formation accompany inflammation,
      wound healing, atherogenesis, and other processes induced by endothelial injury.
      Systems of hemostasis and inflammation play an important role in the pathogenesis
      of acute coronary syndromes. This paper reviews thrombin functions involved in
      its interaction with PAR family receptors, activation of platelets, endothelial
      cells, leukocytes, smooth muscle cells, and mast cells. Mechanisms of regulatory
      effects of thrombin on mast cells associated with nitric oxide release are
      discussed.

PMID- 11240388
TI  - Nuclear melatonin receptors.
AB  - Current opinions on the potential role of orphan nuclear retinoid receptors of
      the ROR/RZR subfamily in regulatory activities of the pineal gland hormone
      melatonin are reviewed. The mechanisms of receptor--DNA interactions and known
      coactivators, tissue peculiarities of the expression of different receptor
      isoforms, and its regulation are described. The spectrum of probable targets for
      regulation by the receptors, the most promoted of which in this aspect being the
      immune and central nervous systems, is traced. It is clear that for final
      "adoption" of the orphan ROR/RZR receptors, there is need for a full
      collaboration of endocrinologists for solution of the still debatable questions
      whether and under which situations melatonin does serve as a physiological
      modulator of the activities of these receptors.

PMID- 11240389
TI  - Thermodynamic stability and functional activity of tumor-associated antibodies.
AB  - Tumor-associated antibodies of human IgG1 subclass were eluted from cell-surface
      antigens of human carcinoma cells and studied by differential scanning
      calorimetry and binding to local conformational probes, protein A from
      Staphylococcus aureus and a monoclonal antibody targeted to the CH2 domain of the
      Fc fragment. At pH 2.0-7.0, we observed virtually identical enthalpies of thermal
      unfolding for IgG1 from normal human sera and tumor-associated IgG1. The exact
      values of calorimetric enthalpy (Delta h) at pH 7.0 were 6.1 and 6.2-6.3 cal/g
      for IgG1 from normal serum and IgG1 from carcinoma cells, respectively. The
      affinity constants of protein A binding to the CH2--CH3 domain interface
      demonstrated differences between serum IgG1 and tumor associated IgG1 that did
      not exceed 3-8-fold. The binding affinity toward the anti-CH2 monoclonal antibody
      determined for serum IgG1 and IgG1 from carcinoma cells differed not more than
      2.5-fold. The thermodynamic parameters of IgG1 from carcinoma cells strongly
      suggest that protein conformational stability was essentially unaltered and that
      the Fc fragment of the tumor-derived IgG1 preserved its structural integrity.

PMID- 11240390
TI  - Unusual behavior of membrane somatic angiotensin-converting enzyme in a reversed
      micelle system.
AB  - Properties of the membrane and soluble forms of somatic angiotensin-converting
      enzyme (ACE) were studied in the system of hydrated reversed micelles of aerosol
      OT (AOT) in octane. The membrane enzyme with a hydrophobic peptide anchor was
      more sensitive to anions and to changes in pH and composition of the medium than
      the soluble enzyme without anchor. The activity of both forms of the enzyme in
      the reversed micelles significantly depended on the molarity of the buffer added
      to the medium (Mes-Tris-buffer, 50 mM NaCl). The maximum activity of the soluble
      ACE was recorded at buffer concentration of 20-50 mM, whereas the membrane enzyme
      was most active at 2-10 mM buffer. At buffer concentrations above 20 mM, the rate
      of hydrolysis of the substrate furylacryloyl-L-phenylalanyl-glycylglycine by both
      ACE forms was maximal at pH 7.5 both in the reversed micelles and in aqueous
      solutions. However, at lower concentrations of the buffer (2-10 mM), the membrane
      enzyme had activity optimum at pH 5.5. Therefore, it is suggested that two
      conformers of the membrane ACE with differing pH optima for activity and limiting
      values of catalytic constants should exist in the reversed micelle system with
      various medium compositions. The data suggest that the activity of the membrane
      bound somatic ACE can be regulated by changes in the microenvironment.

PMID- 11240391
TI  - Evaluation of hexose monophosphate shunt activity in isolated murine lens by
      monitoring the potential of the ferricyanide--ferrocyanide system.
AB  - A method for evaluation of the activity of the hexose monophosphate shunt (HMS)
      in isolated lens is presented. The measurement of HMS activity is based on
      continuous monitoring of the potential of the ferricyanide--ferrocyanide system
      (where ferricyanide is an artificial electron acceptor) in the presence of a
      lens. The rate of reduction of ferricyanide increased after the addition of
      methylene blue (MB) or saponin. The ferricyanide reduction rate did not correlate
      with GSH content in the contralateral lenses of the same mouse in the absence of
      MB or saponin. Correlations between the ferricyanide reduction rate and GSH
      content in the lens were 0.67 (beta = 0.93) in the presence of MB and 0.82 (beta
      = 0.95) in the presence of saponin. We think that the measured curves of
      ferricyanide reduction are representative of: 1) normal level of HMS activity (in
      the absence of methylene blue and saponin); 2) maximal HMS activity (in the
      presence of methylene blue); 3) the intracellular concentration of reducing
      equivalents (in the presence of saponin).

PMID- 11240392
TI  - Effect of zinc ions on conformational stability of yeast alcohol dehydrogenase.
AB  - Yeast alcohol dehydrogenase preparations were prepared with the conformational
      zinc ion removed (Apo-I YADH) and with both the conformational and catalytic zinc
      ions removed (Apo-II YADH). The unfolding of Apo-I YADH and Apo-II YADH during
      denaturation in urea solutions was then followed by fluorescence emission,
      circular dichroism, and second-derivative optical spectroscopies. Compared with
      the native enzyme, Apo-I YADH incurred some slight unfolding, and its stability
      against urea was markedly decreased, while Apo-II YADH incurred marked unfolding
      but contained residual ordered structure even at high urea concentrations. The
      results show that native YADH is more conformationally stable against urea
      denaturation than Apo-I YADH, indicating that the conformational Zn(2+) plays an
      important role in stabilizing the conformation of the YADH molecule. However,
      unfolding of the region around the conformational zinc ion is shown not to be the
      rate limited step in the unfolding of the molecule by the fact that the unfolding
      and inactivation rate constants of native and Apo-I YADH are the same. It is
      suggested that the catalytic zinc ion is more important in maintaining the
      structure of YADH. YADH lost its cooperative unfolding ability after the zinc
      ions were removed. The shape of the transition curves of Apo-I YADH suggests the
      existence of an unfolding intermediate. For both native and Apo-I YADH,
      inactivation occurs at much lower urea concentrations than that needed to produce
      significant conformational changes of the enzyme molecule. At urea concentration
      above 4 M, the inactivation rate constants are much higher than those of the fast
      phase of the reaction of unfolding. These results support the suggestion of
      flexibility at the active site of the enzyme (C. L. Tsou (1986) Trends Biochem.
      Sci., 11, 427-429; (1993) Science, 262, 308-381).

PMID- 11240393
TI  - Receptor-mediated transfer of DNA--galactosylated poly-L-lysine complexes into
      mammalian cells in vitro and in vivo.
AB  - With the goal of developing non-viral techniques for exogenous gene delivery into
      mammalian cells, we have studied receptor-mediated gene transfer using complexes
      of plasmid DNA and galactosylated poly-L-lysine, poly(L-Lys)Gal. To evaluate the
      optimal parameters for efficient gene transfer into human hepatoma HepG2 cells by
      the DNA-poly(L-Lys)Gal complexes, the bacterial reporter genes lacZ and cat were
      used. Examination of the reporter gene expression level showed that the
      efficiency of DNA delivery into the cells depends on the structure of DNA--poly(L
      Lys)Gal complexes formed at various ionic strength values. The efficiency of DNA
      transfer into the cells also depends on DNA/poly(L-Lys)Gal molar ratio in the
      complexes. Plasmid vector carrying human apolipoprotein A-I (apoA-I) gene was
      injected as its complex with poly(L-Lys)Gal into rat tail vein. Some level of
      ApoA-I was detected in the serum of the injected rats. Also, the human apoA-I
      containing plasmid was found to be captured specifically by the rat liver cells
      and transported into the cell nuclei, where it can persist as an episome-like
      structure for at least a week. After repeated injections of DNA--poly(L-Lys)Gal
      complexes, the level of human ApoA-I in rat serum increases, probably, due to
      accumulation of functional human apoA-I gene in the liver cell nuclei. The data
      seem to be useful for the development of non-viral approaches to gene therapy of
      cardiovascular diseases.

PMID- 11240394
TI  - Comparative study of the action of bovine duodenal proteinases (duodenases) on
      polypeptide substrates.
AB  - A comparative study of substrate specificity of bovine duodenal proteinases-
      chymotrypsin-like duodenase (ChlD) and dual-specificity duodenase (dsD)--was
      carried out using oligopeptide substrates (human proinsulin, glucagon, melittin,
      angiotensinogen fragment 1-14). ChlD displayed mainly chymotrypsin-like
      properties towards these substrates, hydrolyzing peptide bonds carboxy-terminally
      to bulky aliphatic or aromatic residues. In melittin, ChlD additionally cleaved
      peptide bonds after Thr and Ser residues. Dual-specificity duodenase (dsD)
      significantly restricted its specificity to only trypsin-like or only
      chymotrypsin-like or displayed full activity, combining both specificities,
      depending on substrate. Both ChlD and dsD efficiently hydrolyzed a single peptide
      bond (Phe8--His9) in angiotensinogen fragment 1-14. The kinetic parameters of
      angiotensinogen fragment 1-14 cleavage by ChlD and dsD were determined
      (k(cat)/K(m) = 80,500 M(-1) x sec(-1) for ChlD and 103,000 M(-1) x sec(-1) for
      dsD).

PMID- 11240395
TI  - Effect of jasmonic, salicylic, and abscisic acids on [(14)C]leucine incorporation
      into proteins of pea leaves.
AB  - All investigated exogenous phytohormones (jasmonic, salicylic, and abscisic
      acids) induced the appearance of (14)C-label in a polypeptide with molecular mass
      29 kD that was not found in the control; these acids also increased
      [(14)C]leucine incorporation into a 25-kD polypeptide and decreased such
      incorporation into a 45-kD polypeptide. This can be considered as a nonspecific
      response of the plants to the action of these hormones. Salicylic and abscisic
      (but not jasmonic) acids induced the synthesis of a 19-kD polypeptide, and
      jasmonate induced the synthesis of a 96-kD polypeptide.

PMID- 11240396
TI  - Dicarboxylic and fatty acid compositions of cyanobacteria of the genus
      Aphanizomenon.
AB  - The occurrence of dioic, hydroxy, branched, and unsaturated fatty acids in
      cyanobacteria of the genus Aphanizomenon growing in different freshwater lakes
      has been studied. Unusual dicarboxylic (from 4.52 to 7.14%) and other fatty acids
      were identified by gas chromatography/mass spectrometry (GC/MS).

PMID- 11240397
TI  - Regulation of heme oxygenase activity in rat liver during oxidative stress
      induced by cobalt chloride and mercury chloride.
AB  - Activities of heme oxygenase and tryptophan-2,3-dioxygenase and cytochrome P450
      content in liver as well as absorption of the Soret band and optical density at
      280 nm in serum were determined 2 and 24 h after administration of HgCl(2) and
      CoCl(2) and after co-administration of the metal salts with alpha-tocopherol.
      Administration of HgCl(2) and CoCl(2) increased the contents of hemolysis
      products in the serum, induced heme oxygenase, and decreased cytochrome P450
      content in the liver. Injection of HgCl(2) increased the activity of tryptophan
      2,3-dioxygenase holoenzyme and enzyme saturation with the heme, but
      administration of CoCl(2) decreased these parameters. Pretreatment with alpha
      tocopherol completely blocked the changes induced by HgCl(2) after 24 h.
      Induction of heme oxygenase induced by CoCl(2) was not blocked by alpha
      tocopherol, but this antioxidant normalized the increase in the level of
      hemolysis products in the serum and decrease in tryptophan-2,3-dioxygenase
      holoenzyme activity and cytochrome P450 content. Mechanisms of regulation of heme
      oxygenase by mercury and cobalt ions are discussed.

PMID- 11240398
TI  - Bacterial protease ECP32 specifically hydrolyzing actin and its effect on
      cytoskeleton in vivo.
AB  - A procedure for isolation of bacterial protease ECP32 yielding 100 microg of the
      enzyme from 10 liters of the Escherichia coli strain A2 liquid culture has been
      developed. The procedure includes chromatography, ultrafiltration, and PAGE under
      non-denaturing conditions. The purified preparation contained about 80% ECP32 and
      did not exhibit ATPase activity. Polyclonal ECP32-specific antibodies have been
      produced, and a two-stage procedure for the isolation of protease ECP32 involving
      affinity chromatography has been elaborated. Microinjection of the purified ECP32
      into Amoeba proteus cells caused reversible distortions in amoeba locomotion. The
      effect was not observed upon inhibition of the protease activity by the ECP32
      specific antibodies. The results indicate that bacterial protease ECP32 may be
      used for the analysis of actin functions in vivo.

PMID- 11240399
TI  - Effects of extraction of the H-subunit from Rhodobacter sphaeroides reaction
      centers on relaxation processes associated with charge separation.
AB  - Effects of extraction of the H-subunit from Rhodobacter sphaeroides
      photosynthetic reaction centers (RC) on the characteristics of the photoinduced
      conformational transition associated with electron transfer between photoactive
      bacteriochlorophyll and primary quinone acceptor were studied. Extraction of the
      H-subunit (i.e., the subunit that is not directly bound to electron transfer
      cofactors) was found to have a significant effect on the dynamic properties of
      the protein--pigment complex of the RC, the effect being mediated by modification
      of parameters of the relaxation processes associated with charge separation.

PMID- 11240400
TI  - Lactate dehydrogenase activity and insulin and lactate levels at an altitude
      below sea level (-350 m) compared to those at an altitude above sea level (620 m)
      after exercise.
AB  - This study was designed to investigate the effect of exercise at 350 m below sea
      level altitude (-350 m) on the serum levels of lactate dehydrogenase (LDH),
      insulin, and lactate. The study was carried out on ten trained adult males with
      mean age of 23.3 +/- 3.4 years following a 21-km noncompetitive run. Venous blood
      was withdrawn from the subjects before exercise and 5 min post exercise. For
      comparison purposes, a similar study was performed with the same subjects but at
      620 m above sea level (+620 m). The results show a significant increase in LDH
      and lactate levels after exercise only at low altitude (-350 m). Serum insulin
      levels decreased significantly after exercise at both altitudes. These changes in
      serum levels of LDH, insulin, and lactate at different altitudes suggest that a
      type of metabolic adjustment is present that meets energy requirements during
      exercise.

PMID- 11240401
TI  - [Adrenocortical insufficiency in renal amyloidosis].
AB  - Renal involvement in amyloidosis leads to chronic renal failure. Prognosis is
      poor. Although amyloid deposits are frequent in adrenal glands, symptomatic
      adrenal dysfunction is uncommon. We report the case of a 63-year-old man with
      chronic renal failure (serum creatinine: 202 micromol/L) subsequent to
      amyloidosis who was referred to our unit for vomiting, dehydration despite a
      persistent nephrotic syndrome, acidosis, hyponatremia (121 mmol/l) and
      hyperkaliemia (7.1 mmol/l). A synacthen test was performed and disclosed adrenal
      insufficiency. Despite the initiation of substitution therapy, the patient died
      one month later from Addisonian crisis. Features of adrenal insufficiency may be
      masked by those of chronic renal failure, emphasizing the importance of adrenal
      explorations in patients with chronic renal failure due to amyloidosis.

PMID- 11240403
TI  - Clinical studies with home glucose clamping.
AB  - OBJECTIVE: Self-blood glucose control is crucial to improving long term outcomes
      in diabetes. To facilitate this task, we offered patients access to a remote
      computer continuously online for data collection, dosing decision support, and
      medical monitoring. Imbedded algorithms for home glucose clamping were custom
      programmed for each patient. The objectives of the present work were to determine
      what proportion of patients chose to use such support and whether users benefited
      from the effort compared to non-users. RESEARCH DESIGN AND METHODS: A single
      central computer system was used. Algorithms for home glucose clamping were
      custom programmed for each patient by their physician who set glucose targets,
      clamping factors and safety constraints. The systems were voice-interactive and
      required the remote patient to handle only a touch-tone telephone. Patients were
      free to access the system each day to report self-measured blood glucose levels
      or hypoglycemia symptoms together with carbohydrate counting, planned exercise,
      stress, illness or other life-style events. Clinical experience was in patients
      followed for 12 months in samples derived from three health-care environments.
      RESULTS: Some 388 patients were offered access to the system. Sixty percent of
      patients (N=231) actively used the system. Among the 3 study centers, over
      104,000 blood glucose measurements were received during the start-up year. Each
      call was processed instantly and automatically. Patients benefited from the 24
      hours access. Those receiving algorithmic assistance for home glucose clamping
      adjusted daily therapy more effectively: prevalence of hyper-glycemia and hypo
      glycemia fell ~ 2-fold (p<0.05) and glycated hemoglobin levels declined 1.3%
      (p<0.001). CONCLUSIONS: Physicians and patients benefited. Patients with diabetes
      may be receptive to computer assistance. Many can accomplish glucose clamping at
      home and meet targets set by their physicians for self-blood glucose control
      while reducing the incidence of diabetic crises. The centralized system adds no
      costs for the patients and empowers physicians to provide safer and superior
      diabetes care.

PMID- 11240402
TI  - White blood cell count and insulin resistance in patients with coronary artery
      disease.
AB  - White blood cell (WBC) count has been shown as a risk factor for cardiovascular
      disease. Decreased insulin sensitivity has been suggested as the link between
      these two entities. Our aim was to study the potential relation between insulin
      sensitivity and WBC count in patients with coronary artery disease. In order to
      assess insulin sensitivity, we performed 83 insulin suppression tests before and
      after therapy in 50 patients with coronary artery disease. Patients with glucose
      intolerance, arterial hypertension or obesity were excluded. Steady-state plasma
      glucose (SSPG) and insulin sensitivity index (ISI=1 000 x glucose infusion
      rate/SSPG) were considered as a measure of insulin sensitivity. WBC count, blood
      platelets, fibrinogen, microalbuminuria, creatinine, urea and HbA1c were also
      assessed. Simple and multiple correlation analysis were carried out between
      insulin sensitivity parameters and the other variables measured. There were
      significant correlation between SSPG and WBC count (r=0,32: p=0,003) and
      microalbuminuria (r=0,28: p=0,012). We also found statistically significant
      correlation between ISI and WBC count (r=0,27: p=0,015) and microalbuminuria
      (r=0,24: p=0,029). No correlation could be detected between either SSPG or ISI
      and the other variables measured. In multiple regression analysis, WBC count was
      found to be an independent predictor of both SSPG (p<0.01) and ISI (p<0.05). Our
      data show the existence of a significant relationship between decreased insulin
      sensitivity and WBC count in patients with coronary artery disease. The results
      of this study suggest that an elevated WBC count could be postulated as part of
      the insulin resistant syndrome.

PMID- 11240404
TI  - [Effects of physical training on endocrine functions].
AB  - Muscular exercise has an impact on endocrine functions. A single bout of exercise
      (for example, running for 30 minutes) activates certain endocrine systems
      required to maintain body homeostasis. Moreover, the effects of exercise persist
      after the end of exercise, continuing during the recovery period. Training, i.e.
      regularly repeated exercise, can affect endocrine functions by modifying hormonal
      responses to exercise and/or by modifying endocrine functions in resting
      conditions. In other words, endocrine functions adapt to repeated muscular
      exercise. The understanding of such modifications should allow avoiding
      unwarranted hormonal substitution in sportsmen and sportswomen.

PMID- 11240405
TI  - [Doping: effectiveness, consequences, prevention].
AB  - The use of doping is linked with the history of sports. Doping abuse escalated
      until the mid sixties when government and sports authorities responded with
      antidoping laws and drug testing. Today, the details of substances detected in
      controls give a good indication on the importance of doping use. Three classes of
      pharmaceuticals account for most of the positive controls. They are anabolic
      steroids, stimulants and narcotics. Their use can be related with the goal of the
      athletes. Anabolic steroids are mainly used in sports such as bodybuilding or
      weight lifting in order to develop strength. Stimulants are used in sports were
      speed favors performance. All the products that enhance blood oxygen
      transportation are used in endurance sports, their efficacy is not scientifically
      demonstrated, but their use does result in real risks. Several studies have
      evidenced the medical problems resulting from prolonged doping. Doping control is
      impaired by the fact that many products now used, e.g. EPO or rhGH, are not
      detectable. Regular medical examination of athletes could help prevent use of
      doping.

PMID- 11240406
TI  - [Therapeutic management of the dyslipidemic patient].

PMID- 11240407
TI  - [Prevention of cardiovascular disease: how to screen and diagnose dyslipidemia?].

PMID- 11240408
TI  - [Methods for screening and biological diagnosis of dyslipidemia in primary
      prevention - January 2000].

PMID- 11240409
TI  - [Patient information. Guidelines for practitioners - March 2000].

PMID- 11240410
TI  - [Statins: a major therapeutic breakthrough].

PMID- 11240411
TI  - [Fundamental data on atherosclerosis].
AB  - Atherosclerosis, a disease of large arteries is the primary cause of heart
      disease and stroke and is the cause of 50% of all deaths in industrialized
      countries. Epidemiological studies have revealed several important environmental
      (smoking, sedentary life, feeding) and genetic risk factors associated with
      atherosclerosis. Knowledge on molecular and cellular causes of atherosclerosis
      have considerably progressed for 20 years. However, it is highly difficult to
      propose a valuable atherogenesis model because numerous molecular and cellular
      abnormalities interact together to induce atheroma. Nevertheless, over the past
      decade, transgenic animals gave interesting physiopathological models of
      atherogenesis and the opportunity to elaborate a pertinent theory of plaque
      formation. It is now demonstrated that atherosclerosis is not a simple chronic
      degenerescence of vascular wall, depending on age and other risk factors
      (dyslipidaemia, smoking, diabetes) but rather a chronic inflammatory disease,
      which induces plaque rupture and acute cardiovascular disease (myocardial
      infarction and stroke).

PMID- 11240412
TI  - [Mechanisms of action of statins and their pleiotropic effects].
AB  - This brief review and update considers a few aspects of the mechanisms of action
      of statins, especially those related to some of the pleiotropic effects that have
      clinical relevance. The beneficial effect on endothelial dysfunction is a class
      effect that is related not only to the lowering of plasma LDL-cholesterol but
      also to a direct effect on nitric oxide (NO) production. It is an early and
      sustained effect, linked to oxidative processes, that deserves particular
      attention since endothelial dysfunction is intimately linked to atherogenesis.
      Awareness of the anti-inflammatory effect came about following the observation
      that statin administration in humans reduces markers of inflammation in the
      circulation. The importance of these observations is ascribable to the fact that
      atherosclerosis is an inflammatory disease, that the inflammatory process in a
      coronary artery is now measurable in vivo in humans, that it contributes to the
      progression and the destabilization of the plaque, and also, because statins
      exert a number of effects that tend to stabilize it. Statins, and particularly
      lipophilic statins, in general inhibit cell proliferation, seemingly by
      multifaceted mechanisms. These include inhibition of cell cycle progression,
      induction of apoptosis, reduction of cyclooxygenase-2 activity and an enhancement
      of angiogenesis. At the center of these mechanisms stands the ability to inhibit
      G protein prenylation through a reduction of farnesylation and
      geranylgeranylation. This effect has been used to show that statins are
      anticarcinogenic in vitro and in animals. The clinical relevance of such a
      property remains to be proven but is supported by promising observations in
      animals and in humans which are detailed in this review. Finally, the ability of
      lipophilic statins to increase the production of bone morphogenetic protein-2
      (BMP-2), and to enhance osteogenesis in animals combined with the results of
      several clinical studies should stimulate physicians to seriously consider an
      eventual indication of statins for the treatment of osteoporosis.

PMID- 11240413
TI  - [Statins and stroke].
AB  - The role of cholesterol in the pathogenesis of stroke, the role of the treatment
      of hypercholesterolemia in the prevention of stroke have been controversed. The
      explanation was based on the heterogenous characteristics of stroke, on the
      relationship between several risk factors, and on the role of the age, in the
      evaluation of these 2 questions. The discovery of statins induced major
      therapeutic trials whose aim was the impact on coronary events. These trials
      demonstrated that statins were accompanied with a major reduction of cholesterol
      levels and stroke events similar to the one observed with coronary events. Even
      prospective, placebo controlled, randomized specific trials for stroke are
      necessary, we can state that cholesterol reduction is the most important
      mechanism accounting for a decrease in stroke occurrence with statins.

PMID- 11240414
TI  - [Kidney and statins].
AB  - Patients with chronic renal diseases (CRD) have a high prevalence of lipid
      abnormalities. Elevated levels of total and low density lipoprotein cholesterol
      are associated with cardiovascular diseases in patients with CRD. The 3-hydroxy
      methylglutaryl co-enzyme A reductase inhibitors appear to be the most effective
      agents to lower LDL cholesterol in this category of patients and are generally
      safe if used with caution. They should be drugs of first choice in CRD but dosage
      reduction and close monitoring may be required to avoid side effects in case of
      renal failure or in combination with calcineurin inhibitors. Moreover recent
      studies suggest that in addition to lowering plasma LDL cholesterol, theses
      compounds may modify several factors implicated in the development of
      atherosclerosis and the progression of chronic renal failure. Such newly defined
      effects may contribute to extend the use of statins in the management of renal
      patients.

PMID- 11240415
TI  - [Statins and diabetic hyperlipidemia].
AB  - Type 2 diabetic patients show frequent lipid abnormalities characterized by
      increased triglyceride and decreased HDL-cholesterol levels, but also by
      qualitative and metabolic abnormalities of all lipoproteins (VLDL, IDL, LDL et
      HDL). Treatment of diabetic hyperlipidemia is important in order to reduce the
      incidence of cardiovascular events, which is high in type 2 diabetes. Treatment
      with statins is recommended when hypercholesterolemia is associated with
      diabetes. But the efficacy of statins in the treatment of the typical diabetic
      hyperlipidemia (hypertriglycerideumia, decreased HDL-cholesterol) remains to be
      demonstrated, since their effects on triglycerides and HDL-cholesterol is
      moderate. However, the new statins (cerivastatine, atorvastatine), which are more
      powerful to reduce hypertriglyceridemia could be useful for the treatment of
      diabetic hyperlipidemia. But, only on going clinical trials with statins in
      diabetic patients will be able to precise their possible efficacy on the
      prevention of cardiovascular disease.

PMID- 11240416
TI  - [Statins: intervention studies, facts and perspectives].
AB  - HMG-CoA reductase inhibitors or statins are potent hypocholesterolemic drugs.
      They associate a dose-dependent diminution of LDL-cholesterol (- 25 to 60%) to a
      raise of HDL-cholesterol (+ 5 to 12%) and a diminution of triglycerides (- 15 a
      30%). Important controlled clinical trials have shown the ability of these drugs
      to reduce - coronary morbidity and mortality in secondary prevention (4S study
      with simvastatin, CARE and LIPID studies with pravastatin). - total mortality in
      secondary prevention (4S and LIPID studies). - coronary morbidity and mortality
      (AFCAPS/Tex-CAPS with lovastatin) and total mortality in primary prevention
      (WOSCOPS study with pravastatin). Questions still remain unanswered. To what
      extent do we have to lower LDL-cholesterol? What are the risks of an aggressive
      treatment with statins? Can we extrapolate the results of the large clinical
      trials to women, elderly, dyslipidemic subjects with other manifestations of
      atherosclerosis (i.e. cerebro-vascular, peripheral vascular diseases)? What are
      the benefits of an early treatment by statins in acute coronary syndromes? Can
      "pleiotropic" effects influence the future indications of statins? These
      questions will be addressed by ongoing studies which will be published within
      five years.

PMID- 11240417
TI  - [Statins and unstable angina: MIRACL].
AB  - Statins have demonstrated their aptitude to lower hypercholesterolemia, and to
      prevent the occurrence of arterial, coronary, and cerebral events, by primary and
      secondary prevention in patients with low or high risk to develop coronary artery
      disease. In the first time, with MIRACL and Atrovastatine, statins are proposed
      in the therapeuty of unstable angina. This study was successful. In fact, in this
      comparative study, high dose of Atrovastatine (80 mg/day) administrated in the
      acute phase of non Q-wave myocardial infarction or unstable angina, reduce
      ischemic events (RR=0.84, p=0.048 ). After anticoagulants and a wide group of
      platelets antiagregants, this statin brings a new agent to the chemotherapy of
      the atherosclerotic unstable lesion. The TACTICS-TIMI 18 and the sub-group of the
      FRISC II study, demonstrate the necessity to stratify the unstable angina risk by
      electric and biologic arguments. They confirm the efficacy of invasive strategy,
      with coronarography, and immediate revascularisation, in patients with high risk
      with persistent modifications of ST segment, and increasing Troponins level.
      Under the cover of a large medical treatment composed of anti-ischemic, Aspirine,
      LMWH, and now a high dose of statins, the acute coronary syndrome invasive
      attitude must be guided by electric, biologic and the invasive attitude
      prognostic risk.

PMID- 11240418
TI  - [Practical questions for the expert].

PMID- 11240419
TI  - [Pyoderma gangrenosum. 15 cases].
AB  - We report a retrospective study of 15 cases of pyoderma gangrenosum. The
      male/female ratio was 2, average age 40 years (range: 2-48 years). The typical
      ulcerous form was observed in 11 patients, whereas bullous pyodrma gangrenosum
      was noted in 2 patients and the granulomatous superficial form in 2 others. The
      leg was the most frequent localization. It was often associated with another skin
      localization. Two patients had neutrophilic pulmonary involvement which was
      concomitant to the skin ulcers. Association with internal disease was found in 8
      patients. Histology showed vasculitis in 11 patients. In 9 of them,
      leukocytoclastic vasculitis was observed. Prednisone and clofazimine were the
      most frequently prescribed drugs. Th rate of recurrence of pyoderma gangrenosum
      was 46% independently of treatment. Occurrence of neutrophilic pneumopathy was
      rapidly fatal in two of our patients

PMID- 11240420
TI  - [Long-term immunologic response in HIV-infected patients with CD4 cell counts </=
      50/mm3 when initiating protease inhibitor therapy].
AB  - From March to July 1996, 61 patients with CD4<50/mm(3)began a therapy with
      protease inhibitors. Increase and maintenance of CD4>100/mm(3) was observed in
      39/61 patients with a protective effect for occurrence of AIDS or death. This
      immunological response was correlated with the duration of the virological
      response. However, 38% of patients with long-term immunological response never
      had a undetectable viral load.

PMID- 11240422
TI  - [Sarcoidosis (first part)].

PMID- 11240421
TI  - [Endocrine disease in adrenoleukodystrophy].
AB  - X-linked adrenoleukodysrophy is the most frequent genetic disorder affecting
      central and peripheral nervous system myelin. One of the biochemical
      abnormalities is the accumulation of very long chain fatty acids (VLCFA) in
      tissues and body fluids subsequent to defective catabolism in the peroxysomes.
      The principal characteristic of the disease is an association between a
      neurological disorder and an endocrine disorder: primary adrenal insufficiency
      and testicular failure. Clinical manifestations are variable. There are two main
      forms, one affecting boys between the age of 5 and 10 years with severe rapidly
      fatal cerebral involvement, and the other affecting young adults between the age
      of 20 and 30 years with degeneration of the anterior and posterior long spinal
      cord tracts, similar to the disorders observed in multiple sclerosis. About 20%
      of the heterozygous women may develop a syndrome which resembles
      adrenomyeloneuropathy, rarely adrenal insufficiency. Adrenal insufficiency is
      present in 85% of the childhood cerebral forms and in about 70% of the adult
      forms. It may occur before, after or at the same time as the neurological disease
      but is not correlated with the severity of the neurological disorder. Careful
      screening is required to avoid missing subclinical forms. Adrenoleukodystrophy
      should be envisaged in young boys with primary adrenal insufficiency, accounting
      for about 30% of the cases of primary adrenal insufficiency in children under 3
      years of age and about 13% of those in adults. Experience with dietary therapy
      (low-VLCFA diet and supplementation with unsaturated fatty acids such as glyceryl
      trioleate (GTO) and glyceryl trierucate (GTE), commonly called Lorenzo's oil) has
      not demonstrated any clinical improvement in the cerebral forms. Bone marrow
      transplantation is recommended for children who show early evidence of cerebral
      involvement. Gene therapy is a promising perspective. Lovastatin and 4
      phenlbutyrate have recently been shown to normalize plasma VLCFA levels. Their
      therapeutic efficacy must be assessed in a randomized trial.

PMID- 11240424
TI  - [Biological manifestations of sarcoidosis].
AB  - Sarcoidosis is a multisystem granulomatous disease of unknown origin. No single
      biological marker allows definitive diagnosis of sarcoidosis or may accurately
      predict the disease prognosis. However, some biological markers are helpful tools
      as diagnostic aids and disease activity markers. At the blood level, lymphopenia
      with CD4 depletion, elevated levels of serum-angiotensin converting enzyme,
      lyzozyme, beta 2 microglobulin and disturbed calcium metabolism resulting in
      hypercalcemia and hypercalciuria can help guide diagnosis. Lymphocytic alveolitis
      with a high CD4/CD8 ratio in bronchoalveolar lavage fluid is highly suggestive of
      the disease. A wide range of new biological markers are proposed but their
      pronostic significance is still controversial. In clinical practice, biological
      markers may help in monitoring treated patients with sarcoidisis.

PMID- 11240423
TI  - [Pathogeny-etiology of sarcoidosis].
AB  - It is now well established that sarcoidosis is a granulomatous disorder resulting
      from an uncontrolled cell-mediated immune reaction in response to unknown
      antigens. This reaction is characterized by the presence of typical granulomas at
      the sites of the disease, made of activated macrophages (epithelioid cells) and T
      lymphocytes. The interactions between both cell types lead to the production of
      numerous inflammatory mediators which are essential for the development of
      granulomas. Recently, sarcoid granulomas have been shown to express a Th1 pattern
      of cytokines. The modulation of the expression of some of them could be useful
      for the development of new therapies. The etiology of sarcoidosis remains
      unknown, but recent advances concerning this disorder suggest that it results
      from various causes involving a particular genetic background and exposure to
      specific environmental factors. Recent data have emphasized in some patients the
      expression of particular HLA haplotypes, the polymorphism of various genes, and
      the presence of oligoclonal T lymphocytes. The characterization of the antigenic
      specificity of these T cells could be helpful in identifying agents responsible
      for the disease. The role of mycobacterial agents is still controversial.

PMID- 11240425
TI  - [Value of imaging in sarcoidosis].
AB  - Imaging plays an important role in identifying thoracic, abdominal and
      neurological localizations of sarcoidosis as well as ENT and bone localizations.
      It contributes to disease detection and is helpful for diagnostic, prognostic and
      therapeutic decision making and useful for therapeutic monitoring. The chest x
      ray is particularly important in the initial work-up and to follow well-tolerated
      disease. Other investigations, depending on the localization, are helpful to
      follow the course of severe or chronic sarcoidosis.

PMID- 11240426
TI  - Sarcoidosis: the nephrologist's view.

PMID- 11240427
TI  - [Atypical forms of sarcoidosis].
AB  - Many atypical forms of sarcoidosis have been described. mediastinum-lung
      involvement, observed in 90% of the cases, may cause atypical manifestations:
      hemoptysis, chest pain, predominant pleural or proximal bronchial involvement.
      Diffuse "unpolished glass" images or air cavities may be observed on the chest x
      ray. A rigorous diagnostic work-up is necessary for these atypical forms.
      Pathological confirmation is mandatory: non-caseous tuberculoid granuloma. A very
      wide range of extra-thoracic localizations have been described with variable
      clinical manifestations. In cases with no mediastinum-lung involvement, pathology
      data must be confronted with the notion of multiple organ dissemination to reach
      diagnosis.

PMID- 11240428
TI  - [Renal clear-cell carcinoma with X;1 translocation revealed by microscopic
      hematuria in a 23-year-old woman].
AB  - Microscopic hematuria is an uncommon inaugural sign of kidney tumors in young
      asymptomatic patients. Renal clear-cell carcinoma was diagnosed in a 23-year-old
      female explored for microscopic hematuria. Radical nephrectomy removed a 7-cm
      tumor without local extension. The cytogenic study of the tumor disclosed X;1
      translocation. The patient also had IgA deficiency. Von Hippel-Lindau disease or
      a cytogenetic abnormality in the tumor are to be searched for in young adults
      with renal clear-cell carcinoma.

PMID- 11240429
TI  - [Rare association of hypoparathyroidism and mediastinal-pulmonary sarcoidosis].
AB  - We report the case of a 52-year-old woman who presented hypoparathyroidism and
      sarcoidosis. The hypoparathyroidism developed 8 years after the diagnosis of
      sarcoidosis. No element in favor of an autoimmune disease of the parathyroid
      could be evidenced. Pathology and immunology blood tests were equally
      noncontributive. Another pathophysiological mechanism, possibly sarcoidic
      granulomatous infiltration of the parathyroid glands, was suspected. The patient
      also presented apparently coincidental vitiligo.

PMID- 11240430
TI  - [Cutaneous pyoderma gangrenosum with hepatosplenic localization and monoclonal
      gammapathy. A case report].
AB  - Pyoderma gangrenosum is an ulcerative disease of the skin. The histopathological
      lesions are nonspecific, characterized by a diffuse neutrophilic infiltrate in
      the dermis. Pyoderma gangrenosum is associated with inflammatory, digestive or
      articular disease, or acute or chronic hemotology disorders in 50% of the cases,
      more rarely with monoclonal gammapathy. A visceral localization of pyoderma
      gangrenosum is rare, simulating a systemic disease or an underlying neoplasia. We
      report a case of cutaneous pyoderma gangrenosum with splenic and hepatic
      localizatios associated with an IgG monoclonal gammapathy. We emphasize the
      efficacy of immunosuppressor treatment and the importance of long-term monitoring
      of these patients.

PMID- 11240431
TI  - [Recurrent acoustic neurinoma after complete surgical resection].
AB  - BACKGROUND: Mortality of acoustic neurinoma surgery is currently very low, well
      below the figures reported by the first surgeons. Morbidity has also declined
      with attempts at preserving the facial function and more recently hearing
      function. Long-term follow-up has demonstrated the well-known risk of recurrence
      after partial resection, but also evidenced a risk after complete resection.
      PATIENTS AND METHODS: We reviewed two series of patients, the first including 40
      patients treated and followed at the Timone Hospital since 1975 and the second
      including 97 operated patients who were followed by the ENT Federation over 8 to
      16 years. We studied recurrence after partial and complete resection. RESULTS:
      Recurrence rate was 20% after partial resection and 9.2% after complete
      resection. DISCUSSION: The 20% recurrence rate after partial resection was
      similar to that reported in the literature. After total extirpation, our 9.2%
      recurrence rate appears well above the 1% reported by others. Although our series
      could have a bias due to the large number of patients lost to follow-up, the
      large population size and the fact that we had a majority of large tumors would
      suggest that recurrence rate is generally underestimated. An 8 to 10% rate
      appears to be closer to reality. Most recurrences were late, with a peak around 8
      years. We did however observe recurrences as early as 1 year and as late as 20
      years. Delay appears to be shorter after partial removal. A wide range of
      localizations were observed but two areas predominated: the internal auditory
      canal and the components of the acousticofacial pedicle, and to a lesser degree
      the brain stem. Most patients were asymptomatic. The principal manifestations
      were balance disorders or trigeminal nerve lesions, more rarely facial palsy. But
      these clinical signs came late and generally signaled a bulky tumor measuring
      more than 3 cm. CONCLUSION: These findings lead us to insist on the need for
      radiological monitoring of all operated neurinomas irrespective of the initial
      surgery. MRI appears to be more accurate than computed tomography. Images must be
      interpreted carefully due to possible postoperative remodeling. For us, these
      observations point to the need for prolonged follow-up of at least 8 years,
      longer for young subjects, for all patients undergoing surgical resection of an
      acoustic neurinoma.

PMID- 11240432
TI  - [Hearing disorders screening in neonates at risk].
AB  - The present report concerns a three year, eight month hearing screening in 1 531
      high-risk neonates by means of two successive transient evoked otoacoustic
      emissions (TEOAE) recordings followed, cin cases of suspected hearing loss, by
      brainstem auditory evoked potential (BAEP) recording and otolaryngology (ORL)
      consultation. After TEOAE1 and 2 and BAEP testing, 1 361 infants (88.9%) were
      declared normal, and 170 (11%) suspected of hearing loss. Of these 170, 58 showed
      bilateral and 26 unilateral impairment. Definite hearing loss on ORL consultation
      was diagnosed in 14 infants (0.9% of the screened population as a whole); 22 are
      still followed, while 86 (5.6%) failed to consult for diagnosis. The mean age on
      diagnosis of definite hearing loss on ORL consultation was 9.9 +/- 4.9 (range 4
      20) months. Several auditory function risk factors have been proved to be more
      frequent in deaf than in normal children. Our results show that early hearing
      loss screening in at-risk neonates needs to be pursued.

PMID- 11240433
TI  - [Otosclerosis in populations living in northern Tunisia: epidemiology and
      etiology].
AB  - Otosclerosis is a hereditary disease frequently encountered in Caucasian
      populations (0.1 to 2% prevalence). In Tunisia, prevalence varies from 0.4% to
      0.8%. The presence of a genetic factor associated with hormonal, biochemical or
      environmental factors, probably lead to variable expression of the otosclerosis
      according to age and sex. Mean age at onset of disease is 25 years (range 16-35
      year) for 61.5% of affected women. In men this proportion is 50.2%. The incidence
      of otosclerosis is high in the 26-35 year age group. Our study showed that in
      northeastern areas of Tunisia, women in this age group were affected twice as
      often as men in this age group. This probably suggests that an endocrine
      mechanism is involved in disease etiology. However, in northwestern areas, there
      was no significant difference between the rates of otosclerosis between sexes.
      Geographical distribution of affected subjects according to the ethnic origin of
      their parents showed that the areas with the highest concentration of affected
      individuals were urban or seaside areas such as the gouvernorate of Nabeul. The
      frequency of otosclerosis was lower in rural areas and/or areas far from the
      seaside.

PMID- 11240434
TI  - [Mandibulotomy for cancer of the oral cavity and oropharynx: functional and
      carcinologic outcome in 107 cases].
AB  - We report a series of 107 patients who underwent mandibulotomy at the Gustave
      Roussy Institute, France for cancer of the oral cavity and orophaynx between 1998
      and 1996. The most common tumor site was the base of the tongue. Most cases were
      stage T2 or T3. Postoperative radiotherapy was employed except in those who had
      previous irradiation, either for the same tumor (12 cases) or another cancer (16
      cases). The different types of mandibulotomies and osteosynthesis methods were
      analyzed in relation to postoperative course and functional and oncological
      outcome at mean follow-up of 6 years. Osteitis was the most frequent complication
      (14%) requiring hemimandibulectomy in 5 cases. Complications occurred
      particularly when osteosynthesis was in the pre-or postoperative irradiation
      field. Osteosynthesis was definitive in 79.4% with good functional results in
      76.5%. Previous radiotherapy or use of flaps for closure gave poor function
      results. We emphasize the advantages of anterolateral mandibulotomy and titanium
      plates. The local control rate was 81.5% at 6 months and overall survival rat was
      51.5% at 5 years with no significant impact of tumor site on survival.

PMID- 11240437
TI  - [Teratoma of the rhinopharynx and the infratemporal fossa in neonates: report of
      3 cases].
AB  - Teratomas are tumors which develop in childhood or early adulthood, generally in
      the gonads. More rarely these tumors may be found in an axial localization,
      notably in cervicofacial forms. We report three cases of teratomas observed in
      rhinopharynx of three neonates operated at the Clocheville General Hospital. We
      present the main anatomoclinical features of these tumors, focusing on the
      cervicofacial forms in neonates. All three cases occurred in female neonates
      presenting acute dyspnea within the first hours of life, requiring intubation in
      two cases. The first two tumors invaded the infratemoral region and the third was
      a pediculated tumor of the velum exteriorized via the mouth. In one case
      antenatal ultrasound had suggested the diagnosis of a right temporomaxillary
      tumor. Rapid excision of the rhinopharngyeal component allow extubation for the
      two intubated infants and pathology diagnosis. In the first infant operated at 2
      months, the lateral route was adapted to age, with mandibulotomy with section of
      the coronoid process but preserving the mandibular condyle. The second infant was
      operated at the age of 3 weeks using a wide frontotemporoperitonial approach then
      at the age of 3.5 months for recurrence extending to the floor of the temporal
      fossa and the middle ear. A type C infratemporal approach was used with lost-bone
      temporal craniectomy. Per-buccal excision was possible in the third infant with
      resection at the base of implantation. No recurrence has been observed in the
      first two cases at 3.5 and 2.5 months follow-up in the first two cases. The third
      infant was lost to follow-up.

PMID- 11240435
TI  - [Computer-assisted video-endoscopic endonasal surgery].
AB  - To make the surgical procedure safer and more precise in FESS, a non-invasive
      markerless computer-assisted system (CAS) is described for intra-operative
      navigation whenever the critical regions may be affected by surgical
      manipulation. PATIENTS AND METHODS: Twenty patients with benign diseases of the
      paranasal sinuses were treated by Computer Assisted Video-endoscopic surgery,
      between December 1997 and March 1998. For the determination of accuracy and
      reproducibility of the system, ten anatomical landmarks on each side of the
      paranasal sinuses were chosen and measured. All of these points were identified
      on the direct live video-endoscopy image and compared to those obtained with the
      Optical Digitizing System (Flashpoint 5000(R)), on axial, coronal and sagittal
      view. The Optical Localizer we used detects the position of the relative
      coordinates of two rigid bodies made of IR-LED's each, one rigid body is secured
      to the head' of the patient with a headset, so that patient motion can be
      tracked, and the second rigid body attached to the operating instrument, leading
      to direct localization of the tip of the instrument. We use a markerless, skin
      surface-based registration method, which has the advantage to avoid doing a
      second CT scan examination usually performed to process the position of the
      fiducial markers. We register the data from the patient's usual paranasal CT
      scan. RESULTS: Computer-assisted surgery does not increase significantly the
      duration of the operation. Our markerless skin surface points registration method
      is reliable enabling of the movements patient's head during the procedure.
      Computer assistance can be used in almost any type of endoscopic sinonasal
      procedure. We obtained a registration and calibration accuracy of less than 1.5
      mm in 89.2% of cases. CONCLUSION: CAS enables the surgeon to have a more thorough
      understanding of the complicated anatomy of paranasal sinuses, and may be
      especially helpful in revision surgery when normal anatomic landmarks are
      lacking. Due to the passive optical technology (Passive Polaris(R)), we are
      continuing clinical studies in ENT surgery in order do improve the system and to
      simplify its current management.

PMID- 11240436
TI  - [Optimization of aerosol therapy in otorhinolaryngology: stability and
      granulometry of dexamethasone-gomenol-framycetin solution].
AB  - Nebulization of solutions associating gomenol, dexamethasone and framycetin is
      very widespread in otorhinolaryngology (particularly for the treatment of actue
      laryngitis and post-traumatic laryngitis and rhinitis and for the tracheotomy
      care). A rigorous clinical evaluation is however lacking. The aim of this work
      was to evaluate use of such solutions in comparison with the recommendations
      issuing from the National Session in April 1997 on good practices for aerosol
      therapeutics. Stability and granulometry were studied in order to optimize
      processing. A new formulation and new technical methods of administration are
      proposed in relation to the results of this study and the national
      recommendations.

PMID- 11240438
TI  - [Isolated facial palsy and occult adenoid cystic carcinoma of the parotid].
AB  - We report a case of adenoid cystic carcinoma of the parotid disclosed by facial
      palsy alone. No tumefaction could be detected clinically or at imaging. The
      diagnosis was established at surgical exploration of the facial nerve. Total
      extended parotidectomy was completed by radiotherapy of the tumor site.

PMID- 11240439
TI  - Is renal involvement related to birth weight and adult height?

PMID- 11240440
TI  - Renal involvement is related to body height in newly diagnosed diabetic women
      aged 40 years or over.
AB  - We scrutinized the relation between body height and renal involvement in a large
      population-based sample of newly diagnosed diabetic patients aged 40 years or
      over. The urinary albumin concentration (UAC) was measured in freshly voided
      morning urine in 1,284 newly diagnosed diabetic patients. The course of insulin
      treatment showed that at least 97.6% of the patients could be regarded as Type 2
      diabetic. Linear regression analyses were done with log UAC as dependent
      variable, and height, age, HbA1c, smoking habits, education, occupation, body
      weight and systolic blood pressure as independent variables. Median age was 65.3
      years. In bivariate analyses UAC increased with decreasing height for women (R
      (S) =- 0.090, p =0.028), but not for men (R (S) =- 0.049, p =0.20). After
      backwards elimination in the regression models, height remained in the model for
      women only (p =0.041). Our finding of a relationship between short stature and
      renal involvement in Type 2 diabetic female patients adds to existing evidence
      from studies with non-diabetic and Type 1 diabetic subjects.

PMID- 11240441
TI  - The effect of exercise training on glucose tolerance and skeletal muscle
      triacylglycerol content in rats fed with a high-fat diet.
AB  - The aim of the present study was to evaluate the effect of exercise training on
      glucose tolerance and glycogen and triacylglycerol (TG) content in different
      types of skeletal muscles and in the liver of rats fed with a high-fat diet. From
      8 to 11 weeks of age male Wistar rats were fed with isocaloric standard (control)
      or high-fat diet (HFD--59% calories as fat) and were additionally assigned to a
      sedentary or trained group (4 weeks of training on a treadmill). An intravenous
      glucose tolerance test (IVGTT) with the determination of basal and post load
      insulin was performed before the final tissue sampling. HFD rats developed marked
      hyperinsulinemia. Exercise training improved glucose tolerance and insulin
      response in the control group only (AUC for glucose in control sedentary vs
      control trained, p<0.05; AUC for insulin: control sedentary vs control trained,
      p<0.005). Liver glycogen was significantly lower in the HFD group (p<0.05 vs
      control sedentary) and did not increase after exercise training. Muscle and liver
      TG content was markedly higher in the HFD group in comparison to control
      (p<0.0001 in all cases). Exercise training increased TG content in the control
      group in all examined tissues except white gastrocnemius (p<0.001 in all cases
      compared to sedentary controls), and did not affect tissue TG in the HFD group.
      After exercise training there was still markedly higher tissue TG content in the
      HFD group vs control (p<0.0001 in all cases). We conclude that beneficial
      metabolic effects of training are impaired in high-fat fed rats and that training
      does not completely reverse metabolic disturbances in this group of animals.

PMID- 11240442
TI  - Metformin retention independent of renal failure in intestinal occlusion.
AB  - Metformin is eliminated by the kidneys, and metformin accumulation has always
      been noticed in oligo-anuric patients. We have reported an exception to the rule
      with the case of a metformin-treated patient having metformin accumulation
      contrasting with a mild increase in serum creatinine in the context of a volvulus
      of the sigmoid colon. This case prompted us to examine the association between
      intestinal occlusion and plasma metformin concentrations. For this purpose, we
      developed an experimental animal model of mechanical obstruction of the
      intestine. Rats were pre-treated during 3 weeks via drinking solution at a dose
      of approximately 100 mg/kg/day of metformin. They underwent at day 0 either sham
      operation (n=7) or operation (n=8) to place a plastic tube around the ileum near
      the ileocaecal valve. Metformin administration was pursued on days 1, 2, and 3
      giving a single dose of 100 mg/kg by intragastric gavage. Four days after the
      surgery, i.e. 24 h after the last metformin administration, the surviving
      intestinal obstructed rats (n=8) developed overt intestinal dilation but no
      biochemical abnormality compared to sham-operated animals (n=7; arterial lactate
      concentrations respectively 4.87 +/- 0.63 mmol/l and 3.97 +/- 0.30 mmol/l, NS,
      and serum creatinine concentrations 69.0 +/- 1.7 micromol/l and 68.7 +/- 1.9
      micromol/l, NS). By contrast, there was a striking difference with regard to
      metformin concentrations, decreasing from 2.95 +/- 0.94 mg/l at day 0 to 0.12 +/-
      0.03 mg/l at day 4 (p<0.001) in the sham-operated group but remaining unchanged
      (1.65 +/- 0.76 mg/l and 1.61 +/- 0.51 mg/l) in the operation group. In
      conclusion, this is the first experiment showing that intestinal occlusion may be
      responsible for metformin retention in the absence of renal failure. Whether this
      observation may be relevant to other drugs remains to be established.

PMID- 11240443
TI  - Low HDL-cholesterol: a component of the metabolic syndrome only in the presence
      of fasting hypertriglyceridemia in type 2 diabetic patients.
AB  - The relation between isolated low HDL-cholesterol and the components of the
      metabolic syndrome is poorly known in type 2 diabetes. We evaluated
      cardiovascular risk parameters in type 2 diabetic patients with low HDL
      cholesterol, compared to those with low HDL-cholesterol and hypertriglyceridemia,
      isolated hypertriglyceridemia and normal lipid parameters. Patients with low HDL
      cholesterol/high triglycerides had higher BMI (29.6 +/- 5.7 vs 27.9 +/- 4.4 or vs
      28.1 +/- 5.2 kg/m(2) ), prevalence of obesity (69% vs 55% or vs 54%), higher
      levels of uric acid (339.0 +/- 83.3 vs 303.3 +/- 95.2 or vs 303.3 +/- 89.2
      micromol/l) and C-peptide (0.76 +/- 0.40 vs 0.63 +/- 0.33 or vs 0.63 +/- 0.36
      nmol/l) and number of components of the metabolic syndrome (27% patients with all
      the components) compared to patients with isolated low HDL-cholesterol or normal
      subjects, respectively. A similar pattern of values was evident in patients with
      isolated hypertriglyceridemia. With logistic regression analysis, BMI and uric
      acid levels were significantly associated with the presence of
      hypertriglyceridemia (both isolated or associated with low HDL-cholesterol),
      while patients with isolated low HDL-cholesterol and those without dyslipidemia
      displayed a similar more favourable metabolic pattern. These results indicate
      that low HDL-cholesterol is a component of the metabolic syndrome only in the
      presence of fasting hypertriglyceridemia in type 2 diabetic patients.

PMID- 11240444
TI  - Interest of Clinitek Microalbumin in screening for microalbuminuria: results of a
      multicentre study in 302 diabetic patients.
AB  - A prospective survey was performed in 302 consecutive diabetic outpatients from 3
      French diabetic centres to study the sensitivity and specificity of screening for
      microalbuminuria using Clinitek Microalbumin. Urinary samples with positive (at
      least one +) proteinuria, hematuria, leucocyturia, or nitrates using the
      Multistix strip were excluded from the study. Results obtained with Clinitek
      Microalbumin were compared to those observed with the reference method of the
      biological laboratory of the centre on the same urinary sample. A positive result
      was defined as an albumin-to-creatinine ratio > or =30 mg/g. Results were
      described in terms of sensitivity, specificity, positive and negative predictive
      values and likelihood ratio. Agreement rates were compared with the Kappa test.
      In the study population, 48 patients (17%) had a positive microalbuminuria with
      reference assay. However, different rates were found in each site (25%, 11%, and
      15%, respectively, p<0.001). Using the Clinitek Microalbumin, a positive result
      was found among 86 patients (29%), (39%, 26%, and 23%, respectively). A good
      agreement was observed in the population as a whole (81%, K=0.47 +/- 0.06) and in
      each site (77%, 81%, 84%, respectively). Sensitivity was 79% (82%, 80%, 75%),
      specificity 81% (76%, 81%, 85%), positive predictive value 46% (53%, 35%, 46%),
      negative predictive value 95% (93%, 97%, 95%), and positive likelihood ratio 4.2
      (3.4, 4.3, 5.0, respectively). Due to the excellent negative predictive value,
      these results suggest that Clinitek Microalbumin is a good screening test for
      microalbuminuria. Positive results should be confirmed using a reference assay.

PMID- 11240445
TI  - Short-term streptozotocin-induced diabetes induces blood pressure decrease
      associated with reduced aortic (45)Ca(2+) uptake and selective depression of the
      sustained noradrenergic contraction.
AB  - To test the hypothesis that diabetes can selectively affect the intracellular and
      extracellular components of the noradrenergic vascular response in rats, we
      studied changes in blood pressure, in vitro vascular contraction and (45) Ca(2+)
      uptake in experimental diabetes induced by injection of 60 mg/kg of
      streptozotocin (STZ). One week after induction of diabetes mean blood pressure
      decreased significantly from 106 +/- 3 mmHg to 89 +/- 2 mmHg. After incubation in
      Ca(2+) =1.6 mM, contraction of STZ aortic rings to 10(- 7) M of norepinephrine
      was preserved in its intracellular component (Control: 231 +/- 28, STZ: 274 +/-
      22 mgForce/mgTissue, NS) but depressed in its extracellular component (Control:
      277 +/- 24, STZ: 133 +/- 33 mgForce/mgTissue, P<0.05). Uptake of (45) Ca(2+) in
      the same rings was depressed in both components. Norepinephrine contractions due
      to extracellular Ca(2+) (prior depletion of norepinephrine-sensitive Ca(2+)
      stores) unexpectedly exhibited a initial component whose magnitude in control
      rings was similar to the response due to intracellular Ca(2+) (extra: 503 +/- 65
      mg, intra: 411 +/- 30 mgForce/mgTissue), and was not depressed in STZ
      preparations (399 +/- 62 mgForce/mgTissue). The sustained contraction to
      norepinephrine in extracellular Ca(2+) was significantly reduced in STZ aortas
      (1163 +/- 92 vs. 528 +/- 95 mgForce/mgTissue). We conclude that: 1) Short-term
      streptozotocin-induced diabetes features reduced blood pressure along with
      deficient aortic (45) Ca uptake and contraction to norepinephrine, and 2) Only
      the sustained phase of the norepinephrine contraction, dependent on extracellular
      Ca(2+), was depressed in the diabetic rats and could possibly be associated with
      the observed fall in blood pressure.

PMID- 11240446
TI  - Prediction of major coronary events by coronary risk profile and silent
      myocardial ischaemia: prospective follow-up study of primary prevention in 72
      diabetic patients.
AB  - The aim of this study was to examine the predictive value of coronary risk
      profile (CRP) for major coronary events in patients screened for silent
      myocardial ischemia (SMI). We studied 72 diabetic patients, aged 41 to 65 years,
      recruited consecutively at the Poitiers diabetes clinic. All patients had at
      least one cardiovascular risk factor associated with diabetes mellitus (type 1
      diabetes duration > or =15 years, dyslipidaemia, smoking, hypertension,
      micro/macro-albuminuria). A structured questionnaire, physical examination and
      resting electrocardiogram provided no evidence of coronary heart disease. SMI was
      defined as positive exercise electrocardiogram and/or dipyridamole thallium
      myocardial scintigraphy. CRP was estimated using the Framingham equation adapted
      to the French population. We defined a high CRP value as annual CRP > or =1.5%.
      Major coronary events (MCE) were defined as myocardial infarction, ischaemic
      heart failure, unstable angina or sudden death. Twenty-one patients with type 1,
      and 51 with type 2 diabetes were followed up for 39+/-12 months: 30 women and 42
      men, aged 55+/-7 years with diabetes duration of 16 +/- 11 years (mean +/- SD).
      SMI was detected in 8 patients. Major coronary events occurred in 8 patients, 2
      of whom had SMI. High CRP was found in 18 patients, 3 of whom had MCE. CRP was
      significantly higher in those patients with a major coronary event (1.71 +/- 1.11
      versus 1.03 +/- 0.56%; p=0.048), but not in those with SMI (1.19 +/- 0.72 vs 1.09
      +/- 0.67%; p=0.654). In Kaplan-Meier survival analysis, a high CRP was associated
      with the risk of a major coronary event (log-rank=5.36; p=0.021), whereas SMI was
      not (log-rank=2.02; p=0.155). The cumulative incidence of MCE in those patients
      with high and low CRP was 8.08 (0.49-15.67) vs 2.15 (0.06-4.22) events per 100
      patient year of follow-up, respectively. CONCLUSION: CRP had a good predictive
      value for major coronary events regardless the presence of SMI. Prevention should
      therefore be focused primarily on patients with high CRP, wether or not they have
      SMI.

PMID- 11240447
TI  - beta Cell autoimmunity in a child with M.O.D.Y. (Maturity Onset Diabetes in the
      Young).
AB  - We present the case of a well characterised M.O.D.Y. type 2 diabetes family in
      which one of the children associated beta cell autoimmunity and a HLA DQB1 at
      risk for immune-mediated type 1 diabetes mellitus. The search for autoantibodies
      against beta cell should be considered in cases of genetically defined form of
      diabetes mellitus to exclude the possibility of a concomitant risk to develop
      type 1 diabetes mellitus.

PMID- 11240448
TI  - Implantable insulin pumps: infections most likely due to seeding from skin flora
      determine severe outcomes of pump-pocket seromas.
AB  - Complications at implantation site of implantable insulin pumps may lead to
      premature removal. To elucidate the origins and the outcomes of these local
      adverse events. We investigated seromas of the 'pump-pocket' that have been
      detected for an eight month-period during the follow-up of such-treated forty
      type 1 diabetic patients. At the start of study period, skin bacterial flora was
      sampled at umbilicus and groin, and isolated strains of Staphylococcus
      epidermidis were preserved in specific vials at -20 degrees C. Each time a seroma
      was detected at transcutaneous 45 days-refill of pump reservoir, it was sampled
      for bacterial cultures. Isolated strains of S. epidermidis from seroma were
      genetically compared to preserved strains of corresponding patients using Pulsed
      Field Gel Electrophoresis (PFGE) after genomic restriction by SmaI. Among the ten
      seromas that occurred after a mean time of 9.9 months since implantation, S.
      epidermidis were isolated in five cases. Genetic comparison of isolated strains
      could be performed in three cases. Compared strains showed identical (in 2 cases)
      or closely related (in one case) PFGE profiles. While the five aseptic seromas
      resolved with rest, four infected cases required explantations after one to
      nineteen months in spite of antibiotic therapy and the fifth one persisted
      without impairment under long-term antibiotics. Our results suggest that seeding
      from the skin flora is a key-factor determining the severity of pump-pocket
      complications. We recommend that bacterial investigations of pump-pocket seromas
      should be systematically performed, while prophylactic measures might include
      antibiotic cover for each puncture of the pump-pocket.

PMID- 11240449
TI  - Rare side-effects of fenofibrate.
AB  - Fibrates are widely prescribed as hypolipidemic drugs and are considered as safe.
      We report the case of a 69 year-old woman who probably developed a major allergic
      reaction following a Fenofibrate prescription (generic form) of 300 mg per day.
      Clinical features included asthenia, hyperthermia (40.5 degrees C) and slight
      muscular pain. Biological abnormalities were mildly elevated muscular enzymes and
      pancytopenia rapidly developed. All bacteriologic, virologic, immune and
      radiologic investigations were normal. Evolution was spontaneously favorable with
      Fenofibrate withdrawal. This is the first reported case of major fever and
      pancytopenia following a Fenofibrate prescription. Adverse effects of Fenofibrate
      are briefly reviewed and their usual favorable outcomes following drug removal
      are outlined.

PMID- 11240450
TI  - Is quantitative insulin sensitivity check index, a fair insulin sensitivity index
      in humans?

PMID- 11240451
TI  - [Behavioural and cognitive approach to obese persons].
AB  - We present a description of basic concepts of the cognitive-behavioural approach
      in obese patients with binge eating disorders. In the first place, we propose the
      process leading to a behavioural reorganization. Then, we evoke some components
      of the cognitive restructuring that allow to understand the link between an event
      and binge eating disorders. We also give practical advice to the health care
      providers.

PMID- 11240452
TI  - [Should antiseptics be used for chronic wounds?].
AB  - Using antiseptics is common, it is adequate on safe skin, but no scientific study
      allow their use on break skin. Then, cicatrisation is a complex process with a
      physiological bacteriocycle. Usual antiseptics are responsible of fibroblasts
      destruction and only a short effect on bacteries. So, it is logical not to use
      antiseptics on break skin.

PMID- 11240453
TI  - [Calculation of the absolute cardiovascular risk in practice].
AB  - Epidemiologic studies underline the responsibility of the cumulative effect of
      cardiovascular risk factors on mortality and morbidity. These data have let to
      the elaboration of equations predicting the risk of coronary heart disease. This
      probability, which defines the absolute cardiovascular risk, can be assessed
      using Framingham formula, Laurier-Chau's risk table, derived from the Framingham
      model, Ducimetiere and PROCAM study' prediction models. The main interest of
      these equations is to give the cumulative effect of risk factors. They can be
      used to evaluate the advantages of primary prevention. Equations do not take into
      account several factors, such as body mass index, fibrinogene and lipoprotein (a)
      values, which have an influence on cardiovascular mortality while others are
      studied in their qualitative aspects (smoking status, diabetes). Furthermore,
      equations are not applicable to the whole population. The absolute cardiovascular
      is a useful tool from an epidemiologic and individual standpoint, but the limits
      of the different models must be known.

PMID- 11240454
TI  - [Can the Medical Information Systems Project clinical score be used to class
      hospitals?].

PMID- 11240455
TI  - [The Medical Information Systems Project clinical coding and surgeons: why should
      surgeons code and how?].
AB  - The clinical coding system recently instituted in France, the PMSI (Projet de
      Medicalisation du Systeme d'Information), has become an unavoidable element in
      funding allocations for short-term private and public hospitalization centers.
      Surgeons must take into serious consideration this controversial medicoeconomic
      instrument. Coding is a dire time-consuming task but, like the hospitalization or
      surgery report, is an essential part of the discharge procedure. Coding can in
      the long run be used to establish pricing by pathology. Surgeons should learn the
      rules and the logic behind this coding system: which, not being based on a
      medical rationale, may be somewhat difficult to understand. Choosing the right
      main diagnosis and the comobidity Items is crucial. Quality homogeneous coding is
      essential if one expects the health authorities to make good use of the system.
      Our medical societies have a role to play in promoting and harmonizing the coding
      technique.

PMID- 11240456
TI  - [Surgical pathology costs more in emergencies: a bias in the clinical scoring
      index].
AB  - A retrospective study of all records of patients operated on for biliary
      lithiasis during the years 1995, 1996 and 1997 was performed in a general
      hospital setting to compare the costs of management according to presentation.
      This study shows that acute and chronic cholecystitis have statistically
      significantly different costs. The reimbursement plans, base on diagnostic
      related groups do not take this into account. This system disadvantages those
      centers which preferentially treat acute pathologies.

PMID- 11240457
TI  - [Benign liver tumors].
AB  - With widespread use of ultrasonography, fortuitous discovery of benign tumors of
      the liver raises the question of surgical management in a large number of young
      subjects. In order to obtain certain diagnosis and determine appropriate
      management, avoiding unnecessary surgery for asymtomatic tumors with a benign
      evolution or inversely delaying surgical treatment of malign lesions, the surgeon
      must be aware of the different features of benign tumors, their expected course,
      and the capacity of imaging techniques to provide positive diagnosis. DIAGNOSIS:
      The most frequent benign tumors found in the liver are hemangiomas or angiomas.
      Lesions measuring less than 3 cm are often fortuitous discoveries at
      ultrasonography,: a typical homogeneous hyperechogenic zone is sufficient for
      diagnosis. There are two situations where diagnosis can be difficult: atypical
      hypoechogenic or large remodeled lesions, hepatopathy in the context of a
      malignant disease. Certain diagnosis can generally be achieved with MRI. Cystic
      lesions of the liver are generally biliary cysts. Ultrasonography is the
      examination of choice and is usually sufficient for diagnosis. In certain cases
      there is a differential diagnosis with a young hydatid cyst or a cystadenoma
      although cystadenomas are very rare tumors usually observed in symptomatic middle
      aged women. In case of atypical images, cystic or necrotic malignant tumor should
      also be entertained as a possible diagnosis. Liver cell tumors include adenomas
      and focal nodular hyperplasia (FNH). Adenomas related to estrogen-progestogen
      treatment can lead to two potentially fatal complications (intratumor or
      intraperitonial hemorrhage or more rarely degeneration to hepatocellular
      carcinoma), justifying systematic resection. FNH is on the contrary ten times
      more frequent than adenoma; observed independently of hormone replacement
      therapy, it does not lead to complications and does not require treatment. It is
      crucial to establish the diagnosis of noninvasive FNH in order to avoid
      unnecessary surgery. MRI provides 80% and 95% specificity. If the imaging work-up
      evidences an atypical FNH and/or a non-tumor anomaly, histological proof is
      needed. As the performance and risk of percutaneous biopsy remain to be assessed,
      we prefer laparoscopic large needle biopsy with extemporaneous pathology
      examination. Imaging cannot provide positive diagnosis of adenoma. TREATMENT: The
      rule is abstention from surgery for confirmed diagnosis of angioma, biliary cyst
      or asymptomatic FNH, irrespective of the size. For symptomatic patients, it is
      essential to establish positive diagnosis initially and determine the
      relationship between the signs and symptoms and the tumor before deciding on
      adapted surgery (fenestration, enucleation, hepatectomy). Surgery may be
      necessary for cystadenomas, adenomas or cases of doubtful diagnosis, keeping in
      mind the risk of morbidity and mortality associated with hepatic surgery for
      benign tumors.

PMID- 11240458
TI  - [Laparoscopic abdominal perineal resection for cancer].

PMID- 11240459
TI  - [Side-to-side porto caval anastomosis with stent].

PMID- 11240460
TI  - [Arterial dissection and suture repair].

PMID- 11240461
TI  - [Infected aneurysm of the superior mesenteric artery].

PMID- 11240462
TI  - [Clinical and economic evaluation of laparoscopic surgery for inguinal hernia].

PMID- 11240464
TI  - [American College of Surgeons Congress. Chicago, 22-27 October 2000].

PMID- 11240465
TI  - [Potential association of pseudoexfoliation syndrome (PEX) with age-related
      macular degeneration (ARMD)].
AB  - PURPOSE: Authors report an unexpected association between PEX and ARMD. It was an
      additional result of a study, that analysed possible systemic symptoms of
      pseudoexfoliation material in visceral organs. They reviewed literature data for
      both, concerning epidemiology and physiopathogeny. MATERIAL AND METHODS: We
      conducted an age-and sex matched study of 142 patients in Brittany, 71 PEX and 71
      controls, 31 men and 40 women in the 2 groups. The statistical study was
      performed with Epi Info 6.0 software using the X2 of Mantel-Haenszel Test.
      RESULTS: Statistical positive relation was found between PEX and ARMD (p=0.02),
      both increasing with age. DISCUSSION AND CONCLUSION: Part of epidemiology seems
      to be similar in PEX and ARMD, especially environment role (particularly solar
      radiations), individual factors, and genetic predisposition. For the first time,
      in may 1999, a genetic localization of PEX was discovered on the chromosome II,
      and nearly of one loci of ARMD multiple localizations.

PMID- 11240463
TI  - [63-year-old man who consulted for general altered state and rectal bleeding].

PMID- 11240466
TI  - [A comparative study of the ocular tolerance of 3 timolol-based preparations: the
      influence of preservatives on ocular tolerance].
AB  - PURPOSE: Ophthalmic preparations can cause toxic ocular reactions, often
      associated with the use of preservatives. The aim of this study was to compare
      the ocular tolerance of three ophthalmic preparations based on timolol: a
      preservative free ophthalmic preparation (Timabak) and two other commercially
      available preserved preparations (Timoptol) and Timoptol LP). METHODS: The effect
      of repeatedly instilling eye drops for 28 days on rabbit eyes was assessed in
      vivo by mean of a confocal laser scanning ophthalmoscope. The corneal
      microlesions were selectively marked by fluorescein. RESULTS AND CONCLUSION: The
      overall results show the good ocular tolerance of the three tested products.
      However, a closer comparison between the products brought out differences in the
      extent of lesions among the tested products depending on their composition.
      Indeed the preservative free eye drops appeared better tolerated than the two
      preserved preparations.

PMID- 11240467
TI  - [New epidemiologic approach to intraocular pressure in an Antananarivo
      population].
AB  - PURPOSE: The Malagasy population is a mixture from many ethnic origins. The
      Merina population is generally of Asiatic origin. The purpose of this study was
      to report the main characteristics of Merina intraocular pressure and their risk
      factors. METHODS: Screening was conducted in 1507 apparently healthy subjects
      with no known ocular disease (such as glaucoma) living in Antananarivo.
      Intraocular pressure was measured with a Goldmann tonometer. RESULTS: Males
      predominated (54.81%). The distribution of aplanation pressure followed an
      asymmetrical Gaussian pattern. In the Merina population, mean intraocular
      pressure was low (13.50+/-3.5mmHg, m+/-SD) and increased with age. There was no
      difference by gender. The prevalence of ocular hypertension was 1.43%. It was
      slightly higher in females and increased to the age of 50 years, then decreased.
      Among possible risk factors, only familial glaucoma was significantly frequent.
      CONCLUSION: The mean intraocular pressure in the Merina population is lower than
      the accepted statistical mean and is similar in both sexes. The prevalence of
      intraocular hypertension is also low but glaucoma develops early. Some of our
      data are similar to those observed in western populations (mean intraocular
      pressure increases with age). Other points are similar to the Asian population
      (low mean intraocular pressure and low frequency of intraocular hypertension and
      its progression after 50 years).

PMID- 11240468
TI  - [Evaluation of confocal microscopy in the analysis of the external trabecular
      membrane during deep nonpenetrating sclerectomy].
AB  - PURPOSE: Deep non penetrating sclerectomy (DNPS) is a new filtering surgical
      procedure whose aim is a selective ablation of the external portion of the
      trabecular meshwork (TM) which is involved in the aqueous outflow resistance,
      i.e. the inner wall of Schlemm's canal (SC) and the external trabecular layers,
      especially the cribriform TM. We evaluated, with a confocal microscope, the
      structural characteristics of this part of the TM in glaucomatous patients.
      METHODS: Thirty-six external trabecular membranes (ETM) were obtained from 33
      consecutive glaucomatous patients (mean age: 56.5+/-14.5 years) and from four
      post-mortem normal donors (60.5 +/-7.7 years), which underwent DNPS according to
      the same surgical procedure. Under conjunctival and scleral flaps, the roof of
      the SC was opened and removed. A deeper dissection led to the removal of the
      inner wall of the SC and the adjacent ETM, i.e the TEM, which allowed a
      satisfactory aqueous flow through the remaining internal TM layers. After
      fixation with acetone or triton X100 and immunostaining with anti-fibronectin or
      vimentin antibodies, the samples were analyzed with a confocal microscope (Nikon
      EZ 2000). RESULTS: The mean thickness of the ETM was 34.4+/-7.3 microm in
      glaucomatous eyes, not significantly different from the controls (39.0+/-10.7
      microm). The main characteristic of the glaucomatous ETM membrane is a
      paucicellularity as compared to the controls (respectively 21.6+/-12.1 cells/area
      and 156.1+/-28.8 cells/area). The confocal microscope analysis shows that the ETM
      involves two different portions of the trabecular meshwork. The architectural
      characteristics of the outermost portion of the ETM with its star-shaped cells
      arranged in a homogenous extra-cellular matrix, suggest that it is the trabecular
      cribriform meshwork. The inner portion of the ETM shows cells arranged regularly
      in a fibrillar extra-cellular matrix as described in the corneoscleral trabecular
      meshwork. CONCLUSION: These results confirm the previous reported
      histopathological changes of the glaucomatous TM. The thickness of the removed
      ETM and its structural characteristics show that the ablation of the TM layers
      necessary to obtain a satisfactory aqueous filtration, not only involves the
      cribriform layers but also one of the inner parts of the TM, i.e. the
      corneoscleral TM. This result suggests that aqueous humor resistance not only
      involves the cribriform trabecular meshwork but also a part of the corneoscleral
      trabecular meshwork.

PMID- 11240469
TI  - [Acute optic neuritis in children: clinical features and treatment. A study of 28
      eyes in 20 children].
AB  - PURPOSE: Analyzing a personal series of children with acute optic neuritis (AON),
      we studied MATERIAL AND METHODS: A retrospective study of 28 eyes in 20 patients
      (mean age: 10;7 years), examined between 1982 and 1997, with a follow-up ranging
      from 6 months to 15 years (mean: 5;5 years). We recorded etiologic factors,
      clinical features (ocular and extra ocular), biological results, and neuroimaging
      findings. RESULTS: Initial involvement was uni- or bilateral with poor visual
      acuity (under 20/200 in 22 eyes of 28). Intracerebral inflammation was present in
      9 of 13 cases where MRI was performed. We found a cause in only 7 cases (5 viral
      diseases and 2 recent vaccinations against hepatitis B). Visual recovery was good
      (over 20/25 in 20 eyes of 28) whatever the treatment, but AON recurred in 5
      children. Four children later developed multiple sclerosis. CONCLUSIONS: The
      cause of AON is rarely found. After eliminating an infection, we retained viral
      disease, complication of a recent vaccination against hepatitis B, and
      neurological diseases. MRI was the imaging study of choice. Development of
      multiple sclerosis occurred in 4 cases of 20, the same frequency as in the
      literature. The risk of later development of multiple sclerosis was 20%.
      Progression of AON was often excellent. Nevertheless, corticotherapy was added,
      in form of intravenous boluses followed by decreasing oral therapy for one month.

PMID- 11240470
TI  - [Ocular manifestation of progressive essential telangiectases].
AB  - Generalized essential telangiectasia is a rare skin disorder characterized by the
      development of dilated venules beginning at the lower extremities and
      progressively spreading out to the rest of the body. It is not related to any
      known affection and is therefore considered to be essential. The condition tends
      to affect mostly women in their midthirties. We report the case of a 49-year-old
      healthy man worried by the progressive extension of dilated vessels on the
      conjunctivae of both eyes and the progressive worsening at the condition over the
      last five years. On clinical examination he presented also telangiectasies on
      both arms and legs which had also grown worse over the last five years. All
      further investigations and complementary examinations showed no disease. A
      cutaneous biopsy showed dilated venules in the superior dermis supporting the
      diagnosis of telangiectases. Several differential diagnoses are discussed. With
      confirmation of the clinical diagnosis we started treatment with oral
      tetracycline. Because of the poor response we stopped treatment after a period of
      three months.

PMID- 11240472
TI  - [Benign childhood intracranial hypertension].
AB  - INTRODUCTION: Infrequent in children, benign intracranial hypertension (or
      pseudotumor cerebri) is most often observed in adults. Careful diagnosis requires
      eliminating all the other etiologies of intracranial hypertension. Most often
      medical, its treatment must be rapid to avoid permanent visual loss. However, a
      surgical procedure is necessary when vision is threatened. We present our
      experience with this pathology and discuss its clinical aspects, its etiologies,
      and the physiopathological mechanisms. PATIENTS AND METHODS: We conducted a
      retrospective study on children who presented benign intracranial hypertension
      confirmed by neuroradiological and neurosurgical examinations. These examinations
      also served to specify the responsible etiologies. The ophthalmologic
      examinations, adapted to the child's age and clinical status, included visual
      acuity testing, optic disc evaluation, ocular motility testing, and visual field
      evaluation. Progression of visual acuity and the topic disc was analyzed after
      treatment. RESULTS: The diagnosis of benign intracranial hypertension was
      confirmed in 22 children (12 boys and 10 girls). Clinical presentation included
      headache and visual disturbance such as visual loss and oculomotor nerve palsy.
      Papilledema was present in nearly all cases. Medical treatment was successful in
      7 children; however, the remaining 15 patients required a lumboperitoneal shunt
      because of elevated intracranial pressure, no response to the medical therapy, or
      threatened vision. DISCUSSION: The physiopathological mechanisms of benign
      intracranial hypertension, an uncommon condition in children, are still unclear.
      It can be associated with severe visual loss. All other intracranial or medullary
      expansive lesions should be eliminated before diagnosis. The causes of this
      syndrome are not the same for pediatric and adult patients. Although medical
      therapy is usually sufficient to normalize the intracranial pressure, a
      lumboperitoneal shunt is at times required. The role of the ophthalmologist is
      important in detecting a possible visual loss or papilla abnormality and in
      ensuring proper treatment follow-up. CONCLUSION: Ophtalmologists are involved in
      the detection of pseudotumor cerebri and the monitoring of visual function, an
      important element in evaluating treatment efficacy.

PMID- 11240471
TI  - [Retinal detachment due to macular holes in highly myopic eyes. Prognostic
      factors].
AB  - PURPOSE: To evaluate the prognostic value of axial length and epiretinal membrane
      (ERM) separation during vitrectomy for retinal detachment due to macular hole in
      high myopia. PATIENTS AND METHODS: Thirty-two consecutive highly myopic eyes (31
      patients) with retinal detachment due to a macular hole were retrospectivly
      studied. All eyes underwent pars plana vitrectomy with gas tamponade (C3F8). An
      epiretinal membrane was removed in 9 cases. The 32 cases were divided into 3
      groups: anatomical success after the initial surgery (group 1, 15 cases);
      anatomical success after two surgical procedures without silicone oil (group 2, 5
      cases), and silicone oil tamponade (group 3, 12 cases). RESULTS: Retinal
      reattachment occurred in 15 cases (46.8%) after the initial surgery. The
      difference of axial length between the 3 groups was not significant. The rate of
      anatomical success without silicone oil was 88.8% (8/9 cases) when an ERM was
      peeled and the number of peelings was significantly higher (p=0,04) in group 1
      than in group 3. CONCLUSION: The axial length was not a pronostic factor of
      silicone oil tamponade in this study. The success rate was higher when an ERM was
      peeled. However, considering the technical difficulty in removing the ERM
      completely, gas tamponade seems to be the better initial treatment.

PMID- 11240473
TI  - [Ahmed valve in high-risk glaucoma surgery].
AB  - We used the Ahmed valve for the treatment of 142 eyes with high-risk glaucoma.
      The glaucoma was neovascular in 74 cases, aphakic or pseudophakic in 19 eyes and
      occurred after previous faliure of filtering surgery in 49 eyes. Preoperative
      mean IOP was 31.6+/-10.4 mmHg under topical and/or systemic treatment. The
      success rate (IOP<22 mmHg with only topical treatment) was 56.3% with a mean
      follow-up of 32.4 months. Complications were fewer and milder compared with those
      reported for other types of drainage implants and for other types of antiglaucoma
      procedures.

PMID- 11240474
TI  - [Choroidal neovascularization as a complication following laser treatment of
      central serous chorioretinopathy].
AB  - We report the case of a 39-year old man who presented with central serous
      chorioretinopathy. Two months after diagnosis, argon laser photocoagulation was
      performed. One month later, the patient noticed distortion and a reduction in
      vision revealing a subretinal neovascularization above the fovea next to the
      laser scar. The patient underwent surgical extraction of the neovascular membrane
      and recovered a visual acuity of 20/30. This case report shows a complication of
      laser treatment of central serous chorioretinopathy and underlines the diagnostic
      difficulties of this disease and its treatment modalities. The surgical excision,
      the first reported in this etiology, led to good visual recovery, as is usually
      observed in young patients operated on for neovascular membrane.

PMID- 11240475
TI  - [Cogan's syndrome. A case report].
AB  - Cogan's syndrome is an inflammatory disease that is characterized by ocular
      inflammation (typically interstitial keratitis) and is associated with Meniere
      like vestibuloauditory dysfunction. Ocular inflammation usually resolves after
      several weeks or months but deafness is often irreversible. We report on a case
      of Cogan's syndrome in a 23-year-old woman who initially presented with bilateral
      anterior uveitis, an unusual clinical feature for this disease. We discuss the
      clinical aspects, the pathogenic mechanisms, the laboratory investigations, the
      differential diagnosis, and the treatment of Cogan's syndrome.

PMID- 11240476
TI  - [Therapeutic approach to congenital cataract].

PMID- 11240478
TI  - [Open disk drusen].

PMID- 11240477
TI  - [Photodynamic therapy and age-related macular degeneration in 2000].

PMID- 11240479
TI  - [Neovascular glaucoma following proton-beam therapy. Case report].
AB  - A 52-year-old-male patient was treated for a posterior choroid melanoma of the
      right eye. When it was diagnosed, it measured 6mm in thickness and 11.9mm for the
      largest diameter and had a typical mushroom shape. General investigations found
      no metastatic disease. It was treated with proton-beam irradiation. Seven years
      later, the patient experienced increased intraocular pressure associated with
      cataract and pain. The patient finally accepted enucleation, as the vision of
      this eye was completely lost and the eye had become painful. Histologic analysis
      of the eye showed changes affecting both the anterior and the posterior segments
      of the eye, mostly related to the tumor and the consequences of treatment.
      Neovascular glaucoma is a major complication that very often leads to
      enucleation.

PMID- 11240480
TI  - [A new procedure for fragmenting the lens with soft-edge micromanipulation during
      phacoemulsification].
AB  - During phacoemulsification: Presentation of a new method of manual nucleofracture
      performed with the use of small-volume and soft-edge micromanipulators. This
      method presents several advantages: During the last three years 1200cataract
      operations have been performed without capsulor rupture and without durable
      endothelial damage.

PMID- 11240481
TI  - [Clinical expert system for diagnosis and treatment of chronic open angle
      glaucoma].

PMID- 11240482
TI  - [Antioxidant effects of mast cell inhibitors in a human conjunctival cell line].
AB  - PURPOSE: The aim of this study was to evaluate in vitro antioxidant effects of
      two mast cells inhibitors. METHODS: Cytotoxicity tests were done on a continuous
      human conjunctival cell line using microplate cold light cytofluorimetry.
      Membrane integrity (neutral red test), DNA condensation (Hoechst 33342 test), and
      reactive oxygen species (ROS) production (dichlorofluoresceine diacetate and
      hydroethidine tests) were evaluated on living cells treated with sodium
      cromoglycate and N-acetyl-aspartyl glutamic acid (NAAGA) preserved (benzalkonium
      chloride: BAC at 0.01%) and unpreserved after 60 minutes of treatment or 60
      minutes and 24 hours of cell recovery. They were tested pure and at a 1/10
      dilution. ROS production was also evaluated after a 60 minute pretreatment with
      antiallergic drugs and a 15-minute treatment with BAC, according to previous
      experiments performed on BAC showing its ROS production properties. RESULTS: No
      cytotoxicity was observed with the unpreserved formulations of antiallergic
      drugs. An apoptotic phenomenom was suggested with preserved drugs after a 1-hour
      treatment, whereas a necrotic mechanism appeared after a 24-hour cell recovery
      period. A ROS production decrease was observed with the two preserved and
      unpreserved drugs tested (p<0.001 compared to BAC) even if it was significantly
      higher with cromoglycate formulations. A ROS production decrease also was
      detected after a pretreatment with antiallergic drugs and treatment with BAC
      (p<0.001 compared to BAC alone). CONCLUSION: In vitro, no cytotoxicity was found
      with the two unpreserved mast cell inhibitors tested. An antioxidant effect also
      was observed with these two molecules; sodium cromoglycate appeared to be the
      best free radical scavenger.

PMID- 11240483
TI  - [Correlation between corneal topography and subjective refraction in idiopathic
      and surgery-induced astigmatism].
AB  - PURPOSE: To study the correlation between subjective refraction and corneal
      topography. To compare the topographic analysis of surgically induced astigmatism
      (cataract and penetrating keratoplasty) with that of idiopathic astigmatism.
      METHODS: Subjective astigmatism, subjective spherical equivalent, best spectacle
      corrected visual acuity (LogMAR units), and videokeratoscopy using the EyeSys
      2000((R)) device (axial, tangential, and refractive power) were recorded in 100
      eyes with idiopathic astigmatism, 100 eyes after cataract surgery, and 100 eyes
      after penetrating keratoplasty. Topographies were classified according to pattern
      (Bogan classification) and asphericity (shape factor: prolate or oblate).
      RESULTS: The asphericity shape distribution was significantly different between
      the 3 groups (p<0.001). The shape of idiopathic astigmatism was almost always
      prolate (90%) whereas the oblate shape was more frequent in the penetrating
      keratoplasty group (75%). There was no significant difference in topographic
      pattern distribution between the 3 groups (p=0.11). The asymmetric bow tie
      pattern was the most common topographic pattern. Topography pattern
      classification was significantly correlated with the subjective astigmatic
      cylinder. (r(s)=0.60, p<0.001). Unlike the round and oval patterns, the bow tie
      pattern was associated with the high subjective cylinder. Correlation between the
      subjective cylinder, the refractive power cylinder, and the axial power cylinder
      was strong (r(s)=0.92 p<0.001), but it was weak for the tangential power cylinder
      (r(s)=0.72 p<0.001). The correlation between the subjective spherical equivalent
      and central cornea power was poor (r(s)<0.37, p<0.001). Subjective astigmatic
      cylinder showed the strongest correlation with best spectacle-corrected visual
      acuity (r(s)=0.70, p<0.001), whereas the predicted corneal acuity, corneal
      uniformity index, asphericity, and refractive power symmetry index were poorly
      correlated with it (r(s)<0.54, p<0.001). CONCLUSION: Despite the difference in
      the asphericity shape, the topographic pattern was similar in the 3 groups. The
      pattern type was significantly correlated with the subjective astigmatic
      cylinder. Topographic indices failed to predict visual acuity, while the
      subjective cylinder showed a strong correlation with visual acuity.

PMID- 11240484
TI  - [Central serous chorioretinopathy and systemic steroid therapy].
AB  - BACKGROUND: The manifestations of the ocular toxicity of systemic corticosteroids
      include posterior subcapsular cataracts and glaucoma. We describe 14 cases of
      serous detachment of the macula due to central serous chorioretinopathy in
      patients given long-term steroid therapy, which may be another potential ocular
      side effect of corticosteroid. CASES REPORT: The 14 (9 men and 5 women) patients
      were aged from 39 to 55 year old. Their systemic diseases were allergic
      thrombopenic purpura, optic neuritis, kidney or heart transplant, Churg and
      Strauss vasculitis, facial palsy, rheumatoid arthritis, systemic lupus and a
      kidney tumor. None of the patients had hypertension. RESULTS: Serous detachment
      occurred between 6 days and 10 years after the start of steroid treatment. The
      higher the doses, the earlier the onset of ocular disease. All patients were
      symptomatic, with rapid onset of blurred vision. Serous detachment was bilateral
      in two cases. The fluorescein angiographic finding was in most cases a single
      small focal hyperfluorescent leak from the retinal pigment epithelium which
      appeared early in the angiogram and increased in size and intensity. No diffuse
      degradation of the retinal pigment epithelium was seen on the fluorescein
      angiogram. Five patients underwent laser photocoagulation of the leaking area
      followed by resorption of subretinal fluid. In other patients, the symptoms
      disappeared as the doses of steroid were reduced. CONCLUSION: The pathogenesis of
      central serous chorioretinopathy remains unclear and is controversial.
      Corticosteroids are known to worsen the prognosis of idiopathic central serous
      chorioretinopathy, and serous detachment has been reported after renal
      transplantation. In most of these cases, chorioretinopathy was combined with
      diffuse leakage from the choriocapillaris. We discuss the relationship between
      steroid therapy and focal leakage as seen in idiopathic central serous
      chorioretinopathy. In conclusion, we describe 14 cases of central serous
      retinopathy whose clinical and fluorescein angiography were fairly typical,
      without obvious diffuse degradation of the retinal pigment epithelium. All these
      patients had been given long-term steroid therapy for various diseases.

PMID- 11240485
TI  - [Motivation of candidates for refractive surgery].
AB  - PURPOSE: To determine the profile and motivations of patients who are candidates
      for refractive surgery. MATERIAL: and METHODS: We studied 102 patients with low
      myopia (less than 6 diopters) in a single-center investigation. RESULTS: Among
      the total population studied, the motivation for refractive surgery was
      essentially comfort and appearance. Fewer men wore contact lenses than women and
      had worn them for a shorter period of time. Those involved in sports were more
      often in individual sports. Contact-lens wearers were most often students or in
      the paramedical professions. DISCUSSION: The population interested in refractive
      surgery was very young. The proportion of candidates who had never worn contact
      lenses was surprisingly high. CONCLUSION: This analysis suggests that patients
      too often consider refractive surgery as an easy option.

PMID- 11240486
TI  - [Inflammatory diseases of the orbit. Highlights].

PMID- 11240487
TI  - Inflammatory diseases of the orbit. Highlights.

PMID- 11240488
TI  - [Ultrastructural features of peripheral choroidal neovascular membranes in age
      related macular degeneration].
AB  - PURPOSE: Some neovascular membranes comprise two parts: a fibro - vascular
      central body and an avascular marginal component. Certain authors have suggested
      that this avascular part could be involved in post laser treatment recurrence of
      subfoveal membranes. The purpose of this study was to determine the
      ultrastructural features of the marginal avascular component. METHODS: Four well
      defined subfoveal neovascular membranes associated with age-related macular
      degeneration were surgically excised. The peripheral portion of each membrane was
      evaluated by transmission electron microscopy for cellular and extracellular
      constituents. RESULTS: Each subretinal neovascular membrane was composed of two
      regions demonstrated by fluorescein angiography: a central area of
      hyperfluorescent leakage and an annular rim of hypofluorescence. The edge of the
      central body corresponded to a richly neovascularized tissue and was surfaced by
      a hyperplasic retinal pigmented epithelium. The rim was composed of a layer of
      retinal pigmented epithelium and a layer of photoreceptor outer segments
      associated with macrophages. The stroma was composed of fibrin and was avascular
      and acellular. DISCUSSION: Neovascular removal of membrane was surgically removed
      as well as native retinal pigmented epithelium beyond the surface of
      fibrovascular central body which could explain why post operative scar surfaces
      were larger than to the initial preoperative membrane defined by fluorescein
      angiography. CONCLUSIONS: The peripheral rim of neovascular membrane is an
      exsudative complication of the outer epithelium made up fibrin, native retinal
      pigmented epithelium, and photoreceptor outer segments. The front of the active
      neovascularization is localized in the periphery of the central fibrovascular
      body.

PMID- 11240489
TI  - [Effect of fluoxetine on histamine content in the rat conjunctiva].
AB  - PURPOSE: To determine the histamine levels of the rat conjunctiva following local
      administration of fluoxetine, a selective serotonin uptake inhibitor. MATERIALS
      AND METHODS: Basal histamine and amine levels were determined in the rat
      conjunctiva following local application of compound 48/80. Fluoxetine was
      administered in the conjunctival fornix of the left eye of the rat, whereas the
      right eye, serving as control, received a drop of vehicle. After one hour, the
      conjunctiva was removed and homogenized, and the tissue histamine content was
      quantified fluorometrically. RESULTS: Histamine levels reached 149.6%+/-11.6 of
      the control eye after local administration of fluoxetine. This increase was
      statistically significant (p<0.004) compared to the control. Simultaneous
      application of the histamine releaser compound 48/80 re-established normal
      histamine levels in the conjunctiva. CONCLUSION: It can be postulated that the
      selective serotonin uptake inhibitors play an important role in the histamine
      concentration of the conjunctiva and in its variations.

PMID- 11240490
TI  - [A full thickness macular hole as an uncommon complication of Behcet disease].
AB  - The authors report the occurrence of an unusual complication of Behcet's disease:
      a full thickness macular hole caused by retinal vasculitis resulting in a
      definite functional impairment. A review of the different ocular complications is
      provided, stressing the unusual location on the posterior segment and the
      potential seriousness of these complications.

PMID- 11240491
TI  - [Orbital lymphangioma. A case report].
AB  - The diffuse form of orbital lymphangioma is well known for its difficult surgical
      treatment. A diffuse orbital lymphangioma was diagnosed in a 6-year-old girl,
      revealed by unilateral recurrent proptosis. The imaging procedure discovered a
      mass presumed to be vascular in nature. The initial incompleted surgical removal
      was followed by 3 recurrences motivating 3 reoperations. Finally, the tumor was
      removed incompletely, with an acceptable reduction of the proptosis. The
      pathologic analyses indicated lymphangioma. Some vascular orbital tumors such as
      lymphangioma, may be very difficult to manage because of local spreading and
      frequent recurrence.

PMID- 11240492
TI  - [Acute lymphoblastic leukemia and vitreous infiltration. A case study].
AB  - The infiltration of the vitreous by acute lymphoblastic leukemia is rare. We
      report the case of a 5-year-old child with acute type-2 lymphoblastic leukemia
      who had a bilateral dense cellular infiltration resulting in significant vision
      loss in both eyes with the child counting her fingers at a distance of 20cm.
      Because the vitreous was not cleared by chemotherapy, we performed a bilateral
      vitrectomy. Vision improved to 6/10 in both eyes and was stable at the 3-year
      follow-up.

PMID- 11240493
TI  - [News on lasers in ophthalmology - Foreword].

PMID- 11240494
TI  - [News on lasers in open angle glaucoma].

PMID- 11240495
TI  - [What to think of "adjuvant" or "neoadjuvant" thermotherapy in the treatment of
      uveal melanomas?].
AB  - Before 810Nm laser thermotherapy has been usd for uveal melanoma, several authors
      especially in Essen (Germany) were asking themselves about the possibilities of
      xenon arc or argon laser effects on uveal melanomas. High rates of recurrences
      due to the non penetration of therapeutic light till the sclera had led to the
      conception of using adjuvant thermotherapy associated with radiotherapy, through
      microwaves, ultrasounds or ferromagnetic seeds. In Leyden (Netherlands) was
      proposed the use of 810Nm laser diode initially as an adjuvant to radiotherapy
      and later on as primary isolated treatment ("neo adjuvant" TTT), especially for
      small tumours located in the posterior pole (juxta-papillary tumours). TTT used
      alone should not be proposed for tumours of inital height of more than 3,5 to
      4mm. "Neo adjuvant" thermotherapy finds some other indications like decompensated
      naevi responsible for macular detachment. Bigger peripheral tumours stabilized by
      protonbeam therapy but associated with persistent detachment after the 12(th)
      month could be treated with "adjuvant" TTT. Finally the importance of the quality
      of the tumour edges treatment should be emphasized.

PMID- 11240496
TI  - [Studies of the hemodynamics of the optic head nerve using laser Doppler
      flowmetry].
AB  - PURPOSE: To study hemodynamics in the optic nerve head (ONH) in animals and
      humans using laser Doppler flowmetry (LDF) during physiological stimuli such as
      flicker light stimulation, variations of the breathing gas (O(2)) concentration,
      and systemic mean perfusion pressure (PP(m)) variations. METHODS: LDF is based on
      the Doppler effect according to which the frequency of the light scattered by a
      moving particle (i.e., red blood cells in the vessels) is shifted in frequency
      compared to that of the incident light. The laser light scattered from the tissue
      and the red blood cells (RBCs) is collected by an optical fiber and fed to
      photodetector. NeXT computer analysis provides relative measurements of the
      Vel(ONH) which expresses the mean velocity of the RBCs, the Vol(ONH) representing
      the number of RBCs and the F(ONH) an expression of the flux of RBCs in the volume
      sampled by the laser. Modifications of the LDF parameters during physiological
      stimuli such as modifications of breathing gas (O(2), CO(2)), flicker light
      stimulation, and variations in the perfusion pressure were studied. RESULTS: The
      results of these studies demonstrated for the first time a dynamic coupling of
      blood flow to function and metabolism in the ONH, mediated by an increase in
      potassium and nitric oxide release. In addition the results of these studies
      showed that the ONH blood remains constant during variations of the perfusion
      pressure (PP(m)) induced by an increase in the intraocular pressure or an
      increase of the systemic blood pressure by isometric exercise. These results
      confirm an autoregulation in the ONH blood flow in animals and humans.
      CONCLUSION: LDF is a powerful technique for investigating changes in blood flow
      in the ONH of anesthetized animals and humans, induced by physiological stimuli
      involving the breathing of various gases, neuronal stimulation, and variations in
      the perfusion pressure. This highly sensitive and reproducible technique opens
      new avenues in the elucidation of blood flow regulation mechanisms in the ONH.

PMID- 11240500
TI  - [Optimizing the archiving of digital angiograms with image processing software].

PMID- 11240499
TI  - [Papillomatous and nevus of the caruncle].
AB  - A 63-year-old male patient was operated of a single conjunctival papillomatous
      lesion located on the left caruncle. The curative tumoral excision was followed
      by its histological analysis. Histologically, the tumor associated an epithelial
      squamous papilloma with a subepithelial nevus, confirming a combination of two
      different lesions.

PMID- 11240502
TI  - [Trisomy 21 screening: value of ultrasound and serum markers in a combined
      approach].

PMID- 11240503
TI  - [Computer analysis of fetal heart rate by the Sonicaid Oxford 8002 System during
      pregnancy and labor. Personal experience and report of the literature].
AB  - Computer analysis of the fetal heart rate (FHR) was first described at Oxford
      University by the late Professor Dawes and by Redman for the prenatal
      surveillance of high risk pregnancies. We present our experience with this
      technique applied to the management of induced prematurity under 32 weeks'
      gestation in a tertiary perinatal center, by comparing our perinatal results with
      the preceding period of visual analysis of the FHR. Our analysis of the
      literature reports the results obtained with this technique in various high risk
      pregnancies and describes the modifications of computerised cardiotocography
      consecutive to obstetrical maneuvers or diverse maternal drug administrations.
      Finally we report our preliminary experience with the recently available Sonicaid
      Team IP System recommended for fetal monitoring during labor.

PMID- 11240504
TI  - [Management of premature rupture of the membranes at term: how long to delay?
      Results of a prospective multicentric study in 713 cases].
AB  - OBJECTIVE: The aim of our study was to define he best delay for management of
      spontaneous rupture of the membranes at term. MATERIALS AND METHODS: We conducted
      a prospective multicentric study in western France defining 3 groups of
      expectancy (6, 12 and 24 hours) to assess obstetrical, neonatal and maternal
      outcomes. RESULTS: We included 713 patients. There was no significant difference
      in neonatal and maternal morbidity between the 3 groups. The rate of cesarean
      section was statistically higher in the 6-hour group (12%). There was no
      statistical difference between 12 and 24 hours but the rate was lower in the 12
      hour group (5.5 versus 7.9%). CONCLUSION: Based on our findings and a review of
      the literature, we have decided that in cased of premature rupture of the
      membranes at term, a 12 hour delay is best. At most two prostaglandin maturations
      can be performed in unfavorable cervixes.

PMID- 11240505
TI  - [Clinical and paraclinical monitoring of a normal pregnancy].
AB  - The objective of this work was to improve physician's knowledge concerning
      medical and laboratory screening practices for pregnant women in France. We used
      the French legislation and the French guidelines on pregnancy screening.

PMID- 11240506
TI  - [Which initial tests should be performed to evaluate meno-metrorrhagias? A
      comparison of hysterography, transvaginal sonohysterography and hysteroscopy].
AB  - OBJECTIVE: Evaluate the feasibility and the value of hysterography,
      sonohysterography and hysteroscopy for investigation of abnormal uterine
      bleeding. Method. Longitudinal blind study of thirty-eight patients consulting
      for abnormal uterine bleeding during pre- and post menopause. All patients
      underwent an hysterography and transvaginal sonohysterography, in random order,
      followed by an hysteroscopy with histological sample. The results were compared
      with the histo-pathological examination that was used for reference diagnosis.
      Statistical study of sensitivity, specificity and Positive and Negative
      Predictive Value (PPV-NPV) of each investigation; rate of agreement by the
      coefficient of Kappa. RESULTS: The hysterography offers a PPV of 83% and a NPV of
      100%. The interpretation errors were associated with the simple mucous
      hypertrophy interpreted as "hyperplasy". The limits correspond to a contrast
      agent allergy. The sonohysterography had a VPP of 89% and a VPN of 100%. The
      false positive is due to the difficulties of distinguishing the clots from the
      polyps. The limits correspond to the difficulties of cervix catheterization
      (13%). As regards the hysteroscopy, the VPP was 81.5% and the VPN of 75%. The
      interpretation mistakes were associated with mucous hypertrophy and the
      hyperplasy. CONCLUSIONS: The most useful examination for abnormal uterine
      bleeding, in the first instance, is transvaginal sonography with saline
      instillation. A complement by Doppler study would probably make it possible to
      limit the false positives.

PMID- 11240507
TI  - [A rare case of epigastric heteropagus twinning].
AB  - Epigastric heteropagus is a very rare form of conjoined twins. It results from an
      ischemic atrophy of the body structure of the monozygotic conjoined twins at an
      early gestational age. Diagnosis is made by prenatal echography which must look
      for congenital heart disease associated in 28% of epigastric heteropagus.
      Cesarean section is indicated to prevent for mechanical dystocia. The autosite
      component of epigastric heteropagus can successfully be treated with early minor
      surgery. Autosite twin survival is good. Discussion with the family is important
      to avoid needless terminations. We report a rare prenatal diagnosis of epigastric
      parasitic twinning in which the parasite had pelvis with lower limbs. At birth,
      the autosite had omphalocele containing only bowel loops from the parasite.

PMID- 11240508
TI  - [Bilateral hydatid cyst of the fallopian tubes: a case report].
AB  - We report an exceptional case of bilateral hydatid cysts that developed solely in
      the fallopian tubes of a young girl. The diagnosis was suggested by the clinical
      history, the patient's residence in an endemic area, and the ultrasound findings
      and was confirmed peroperatively. Due to the extensive damage bilateral
      salpingectomy was required compromising future reproduction potential. We discuss
      the pathogenesis of pelvic localizations and the ultrasound aspects of pelvic
      hydatid cysts.

PMID- 11240509
TI  - [The regional policy, the position in 1999].

PMID- 11240511
TI  - [Physiology and pathophysiology of inflammation].

PMID- 11240512
TI  - [Premature delivery and inflammation].
AB  - Premature delivery results from multiple closely interdependent factors.
      Inflammation is most generally caused by cervicovaginal infection that may
      progress to intra-uterine infection or inflammation. Severe chorioamniotitis is
      found in 75% of all premature deliveries compared with 15% in term deliveries.
      Premature rupture of the membranes is the cause of premature delivery in 30-40%
      of premature deliveries although the diagnosis of chorioamniotitis can also be
      established with intact membranes, sometimes on the basis of histological
      findings alone. The degree of prematurity is correlated with the severity of the
      histological chorioamniotitis. The severity and the duration of the lesions is
      often the cause of antibiotic failure for the treatment of threatening premature
      delivery. Inflammation mediators, mainly proinflammatory cytokines (IL1, TNF
      alpha), chemokines (IL6, IL8 and MIP-1alpha) and immunomodulator cytokines (IL6)
      and immunosuppressive cytokines (IL10, IL4) are produced by the amniotic and
      decidual membranes and are found in the fetal circulation and amniotic fluid.
      This reaction triggers a cascade of events leading to the production of
      prostaglandins and cyclooxygenase (COX2) activity, that cause uterine
      contractions. The inflammation may be initiated locally, even from an extrapelvic
      location, This leads to a fetal and/or maternal systemic inflammatory reaction.
      Systemic fetal expression of deregulated inflammatory phenomena can lead to
      neonatal lesions of lung and brain white matter tissue. This explains the failure
      of tocolysis and antibiotics in uncontrolled situations and suggests new avenues
      for therapy using selective inhibitors of COX2.

PMID- 11240513
TI  - [Maternal inflammation and pre-eclampsia].

PMID- 11240514
TI  - [Effect of perinatal inflammation syndrome on lung maturation and development].
AB  - Despite improvement in neonatal care, the incidence of bronchopulmonary dysplasia
      has not decreased over the last decade. Moreover, chronic lung disease still
      occurs in very premature infants who do not require ventilatory support at birth.
      This review presents the growing body of epidemiological, experimental and
      clinical evidence suggesting that the occurrence of an inflammatory reaction
      triggered in utero or immediately after birth is associated with the subsequent
      development of chronic lung disease. However, stimulators of inflammation or
      specific proinflammatory cytokines may also have beneficial on lung maturation.
      How proinflammatory mediators interfere with lung maturation and alveolarization
      needs to be better understood in order to pave the way for new immunomodulatory
      strategies to prevent chronic lung disease in very preterm infants.

PMID- 11240515
TI  - [Neonatal neurological impact of inflammation in the fetus].
AB  - With improvement of critical care of the newborn, perinatal mortality had
      decreased along the past decades. However, recent studies have shown that there
      is a slightly increase in the prevalence of cerebral palsy over the same period
      either for term or premature babies. Epidemiological data stress the
      multifactorial origins of cerebral palsy. Along with premature birth one of the
      predominant cause appears to be chorioamnionitis. Using data from a review of
      clinical and experimental studies the authors aim to clarify the link between
      infection, inflammation and fetal brain damage. The hypothesis that cytokines as
      mediators of inflammation can also mediate neurotoxicity is developed.

PMID- 11240516
TI  - [Perinatal corticosteroid therapy: modalities, efficacy, consequences].
AB  - During perinatal period, corticosteroid treatment has two major indications:
      first antenatally to improve fetal maturity and then to treat postnatal
      bronchopulmonary dysplasia. Antenatal corticosteroid treatment is widely proved
      to be efficient in reducing hyaline membrane disease and perinatal mortality
      incidence. Moreover, it has positive effects on intraventricular hemorrhage
      incidence, on hemodynamic failure, on persistent patent ductus arteriosus and on
      necrotizing enterocolitis. Side-effects are few and mild considering expected
      benefits and they usually occurs after multiple courses. Contra-indications are
      rare. Bronchopulmonary dysplasia comes with early, important and prolonged
      inflammatory processes. Corticotherapy allows decreasing significantly length of
      mechanical ventilation and oxygenotherapy among ventilated premature infants
      diagnosed with bronchopulmonary dysplasia. In the meantime, acute side-effects
      are frequent and benefits on mortality rate and long term outcome are not
      obvious. Main concern remains on possible long-term deleterious consequences on
      growth, lung and central nervous system development. In this field, clinical data
      are still insufficient as animal experimentation data promote caution and search
      for a minimal efficient therapeutic pathway.

PMID- 11240517
TI  - [Multiple pregnancy, place of delivery and mortality in very premature infants:
      early results from the EPIPAGE cohort in Ile-de-France area].
AB  - OBJECTIVE: To estimate stillbirth rate et neonatal mortality in very preterm
      infants in relation to gestational age at birth, place of delivery, and type of
      birth. PATIENTS AND METHODS: This study includes neonates from the EPIPAGE cohort
      survey, born between 22 and 32 weeks of gestation, in the Paris area from the
      first of February to the 31(st) of July 1997. Stillbirth rate and mortality
      before hospital discharge were studied. Level III facilities were defined by
      facilities that had an obstetric ward and intensive care unit for the newborn on
      the same site. RESULTS: Of the 772 neonates, 58% were born in level III centers.
      This percentage increased to 71% for multiple births. Mortality (stillbirth rate
      and mortality before discharge) of neonates born in level III was lower than the
      observed for neonates born in other centers (22.9% versus 45.8%). This difference
      was mainly due to difference in stillbirth rate and mortality in the delivery
      room. CONCLUSION: Differences in perinatal and neonatal mortality were observed
      between maternity units. It may reflect differences in attitudes. The
      explaination of such differences should be based only on long term outcome.

PMID- 11240518
TI  - [Pediatric follow-up network in the south Ile-de-France].
AB  - Regional organization of perinatal care, with maternal tranfers, has largely
      contributed to the increasing survival rate of very preterm infants.
      Nevertheless, follow-up and care the of these surviving children at risk of
      neurodevelopmental impairment are insufficiently organized. For this reason, a
      pediatric network of care and follow-up has been set up in continuity of a
      regional perinatal network ("reseau perinatal et reseau pediatrique du sud-ouest
      de l'Ile de France"). Two missions are devoted to this network: organize local
      follow-up and care of infants at risk of abnormal outcome and collect follow-up
      data with specific forms. One form per year of age is to be filled with Items
      concerning growth, health, cognitive and motor development, family and society
      integration, quality of life.

PMID- 11240519
TI  - [Pregnancy outcome and infant follow-up after diagnosis of nuchal anomalies at
      the 1st or 2nd trimester ultrasound examination].
AB  - OBJECTIVES: The aim of this study was to determine pregnancy outcome and
      investigate infant follow-up after diagnosis of nuchal anomalies at the first or
      second trimester ultrasound examination in order to identify prognosis factors
      and improve prenatal counseling. PATIENTS AND METHODS: Between January 1994 and
      June 2000, double skin fold 3mm or cystic hygroma at the first trimester
      ultrasound, or thicken nuchal anomaly at second trimester ultrasound explorations
      were diagnosed at the Robert Debre maternity ward. RESULTS: One hundred fifty
      nine pregnancies were terminated and 131 infants were delivered and followed with
      four pediatric examinations during the first two years of life. Among the 131
      newborns, 104 (79%) progressed normally, 16 had a major malformation (heart,
      kidney, skeletal; 9 (6.8%) with a unique anomaly and 7 (5.3%) with malformation
      syndromes), and 14 (10.6%) presented nonspecific retardation of psychomotor
      development either alone (7 cases) or associated with an identified genetic
      syndrome (7 cases). DISCUSSION: Neonates who presented a nuchal anomaly during
      pregnancy are a high-risk population, particularly for retardation of psychomotor
      development which is not always diagnosed during the neonatal period. Careful
      postnatal follow-up is required to identify developmental disorders undiagnosed
      at birth. CONCLUSION: This series is the largest reported in the literature in
      terms of number of infants and also for postnatal pediatric follow-up and
      homogeneous pedratrician follow-up.

PMID- 11240520
TI  - [Value of molecular cytogenetics in pre- and postnatal diagnostic of chromosome
      abnormalities].

PMID- 11240521
TI  - [Information disclosure when screening for trisomy 21: a decision-making aid for
      pregnant women?].
AB  - We examined the contribution to decision-making of the information that is
      disclosed to women confronted with the proposition of screening for Down syndrome
      and when receiving the results. This review highlights the main results of a
      survey initiated by the French Ministry of Health. The purpose of this survey was
      to assess the modalities of prescription and results communication of the test,
      and also to determine the women's opinion concerning the information they had
      received. A large percentage of the women were dissatisfied with the information
      received before the test prescription, a percentage that was even more marked
      when the test results were delivered. Information was frequently regarded as not
      contributing to the decision-making process about testing and the data analysis
      suggested that information may not be adequate to prepare women for the decisions
      implied in the test results. However, a direct relationship cannot be established
      between satisfaction with information and contribution of the information to
      decision making: information may be considered as contributing to the decision
      although women did not understand the explanations; the contribution to decision
      making does not have the same meaning when the test is proposed as a routine test
      (i.e. a self-evident act) or not. Finally, from the women's point of view, to
      make the "best possible" decision would require that health professionals'
      preferences regarding the information to be disclosed converge with the women's
      expectations regarding information, and with their preferences concerning the
      implication of health professionals in the decision-making process. In an
      operational perspective, the use of information and decision-making aid
      instruments could facilitate the elicitation of preferences and expectations.

PMID- 11240522
TI  - [Anoxic encephalopathy of the term neonate and brain hypothermia].
AB  - The outcome of term newborns with birth asphyxia and moderate to severe hypoxic
      ischemic encephalopathy remains very poor. After the primary phase of energy
      failure during asphyxia, neuronal cell metabolism may deteriorate in a secondary
      phase of brain injury. The window between these two phases opens the way to
      potential neuroprotective treatments such as brain cooling. Promising
      experimental data on controlled hypothermia need to be examined with clinical
      trials.

PMID- 11240523
TI  - [Which tocolytics should be used in 2001?].
AB  - Beta-mimetics are the gold standard tocolytic treatment but raise several
      problems. Despite their recognized efficacy in prolonging pregnancy, the neonatal
      benefit remains to be proven. There are several contraindications and frequent
      adverse effects, with a risk of fatal maternal accidents. The lack of reliable
      criteria for the prediction of preterm birth leads to giving unnecessary
      treatments to two-thirds of the patients. In this context, obstetrical practices
      have tended to prefer tocolytics which, with the same efficacy, would have fewer
      side effects than beta-mimetics and which would not raise a risk of severe
      complications. Calcium-channel blockers belonging to the dihydropyridin family
      and ocytocin antagonists would appear to meet the new requirements. In randomized
      trials versus beta-mimetics, they have been found to have a comparable effect in
      prolonging pregnancy by 48 hours. Tolerance is better than with beta-mimetics and
      treatment interruption due to side effects can be avoided. Finally, a meta
      analysis of trials comparing calcium inhibitors versus beta-mimetics demonstrated
      a decrease in respiratory distress syndrome in the neonates and a reduction in
      the number of transfers to neonatal intensive care. The data accumulated on these
      new compounds would appear to suggest that they should be used as the first line
      treatment and not as an alternative to beta-mimetics. Other compounds including
      NO donors and cyclo-oxygenase 2 inhibitors are under evaluation.

PMID- 11240524
TI  - [Acrocyanosis: changing concepts and nosological limitations].
AB  - Acrocyanosis is undoubtedly the most commonplace acrosyndrome, both in terms of
      pathogenesis and prognosis. Patients experience functional impairment and an
      esthetic prejudice that must not be neglected. Adopting the nosological
      classifications described for Raynaud's syndrome, primary acrocyanosis must be
      distinguished from exceptional secondary phenomena that have a radically
      different clinical course. Primary acrocyanosis is generally observed in a young
      woman who appears thin or has recently lost weight. No paroxysmal episode
      (syncope, cyanosis, suspicious event involving the fingers) is found. The
      physical examination is negative and no complementary explorations are needed.
      Current pathophysiological hypotheses remain insufficient but suggest that
      vasospasticity rather than hemorheology is involved. The hypothesis that a
      thermoregulation disorder could be associated with weight loss deserves further
      study. Symptomatic care relies on dietary and hygiene counseling, emphasizing the
      importance of warm clothing. The psychological element must also be considered
      even in the most common forms.

PMID- 11240525
TI  - [Superficial venous thrombosis of the lower limbs: prospective analysis in 100
      patients].
AB  - OBJECTIVES: Our objectives were first to estimate the potential gravity of
      superficial venous thrombosis (SVT) of the lower limbs by determining the
      frequency of associated deep venous thrombosis (DVT), pulmonary embolism (PE) and
      extensions of the junction or a perforating vein and second to identify factors
      of risk (neoplasia, thrombophilia, connective tissue disease, thromboembolic
      events). METHOD: We conducted a prospective study in 100 cases of SVT in 88
      patients with varicose veins (VV) and 12 patients without varicose veins (NVV).
      RESULTS: Superficial venous thrombosis was identified in 32 cases (32%): muscle
      vein in 23 (gastrocnemius, solesu), popliteo-femoro-iliac system in 5, and
      posterior tibial or fibular vein in 4. In 17 cases (17) the SVT extended to deep
      veins at distant localizations in 15 (15%). Pulmonary embolism was suspected
      clinically in 10 cases (10%) and confirmed in 3 (3%). An extension to the
      saphenous junction was observed in 17 cases (17%) and the thrombus migrated into
      a deep vein in 7. There were 6 cases of a unique extension to a perforating vein.
      Search for etiology was conducted in 86 cases: 64 were negative (74.4%), there
      was a neoplasia context in 5 (6%) and a hemostasis disorder in 17 (19.8%)
      including 6/12 (50%) in the NVV group and 11/74 (15%) in the VV group.
      CONCLUSION: Superficial venous thrombosis is often considered to be benign
      although severe situations can occur in patients with a hemostatis disorder.
      Consideration of these different factors (risk factors, presence of a deep venous
      thrombus or pulmonary embolism) should be helpful in determining the etiology and
      for a better choice of a therapeutic option (medical/surgical) depending on the
      different subpopulations identified.

PMID- 11240526
TI  - [Prevalence of duplex ultrasonography detectable venous thrombosis in patients
      with suspected or acute pulmonary embolism].
AB  - OBJECTIVES: Duplex ultrasonography performance in detecting embolic foci has not
      been proven satisfactory compared with phlebography or autopsic findings. In case
      of suspected pulmonary embolism, the embolic focus is only discovered in 11 to
      18% of the cases compared with more than 30% with phlebography. For overt acute
      pulmonary embolism, the discovery rate is in the 30 to 45% range versus 70 to 80%
      with phlebography or autopsy findings. This discrepancy might result from the
      fact that duplex ultrasonographic explorations are generally limited to the deep
      collectors at the cruropopliteal level. The purpose of this study was to assess
      the prevalence of duplex ultrasonography detected venous thrombosis in patients
      with suspected or acute pulmonary embolism when the exploration includes the
      entire venous system from the inferior vena cava to the ankles and examines not
      only the deep collectors but also the muscle and superficial networks. MATERIAL
      AND METHODS: This study included all patients with suspected pulmonary embolism
      referred to the emergency unit from January 1, 1995 through December 31, 1998.
      The patients' hospital files were used to determine the suspected pulmonary
      embolism population. The acute pulmonary embolism population was defined as the
      patients whose files contained documented proof of pulmonary embolism (highly
      probable ventilation/perfusion pulmonary scintigraphy, positive pulmonary
      angiography, positive proximal angioscan). Thrombosis of the deep venous
      collectors with or without associated superficial or muscular localization was
      classed as "deep venous thrombi" and superficial or muscular thrombosis without
      involvement of the deep collectors was classed as "other venous thrombi".
      Subpopliteal thrombosis was classed as distal and popliteal or suprapopliteal
      thrombosis as proximal. RESULTS: The suspected pulmonary embolism group included
      352 patients, 118 men and 234 women aged 67.6 +/- 15.4 and 70.8 +/- 20.0 years
      respectively (m +/- SD). The acute pulmonary embolism group included 60 patients,
      17 men and 43 women aged 66.2 +/- 12.5 and 69.7 +/- 16.6 years respectively.
      Overall prevalence of duplex-ultrasound detected venous thrombosis was 30.4%
      (107/352) (95%CI: 25.6-35.2) in the suspected pulmonary embolism group and 80%
      (48/60) (95%CI: 69.9-90.1) in the acute pulmonary embolism group. Deep venous
      thrombi reaching the collectors and proximal thrombi predominated. Prevalence of
      "other venous thrombi" and distal venous thrombi were 6.5% (23/352) and 11.4%
      (40/352) respectively in the suspected pulmonary embolism group and 15.0% (9/60)
      and 26.7% (16/60) in the acute pulmonary embolism group. The frequency of
      asymptomatic venous thrombosis of the lower limbs, irrespective of the
      localization, was 42.1% (45/107) in the suspected pulmonary embolism group and
      52.1% (25/48) in the acute pulmonary embolism group. CONCLUSIONS: The prevalence
      of duplex-ultrasonography detected venous thrombosis in patients with suspected
      or proven pulmonary embolism found in this series was equivalent to the rates
      reported in phlebography and autopsy series. The prevalence was higher than
      usually reported for duplex-ultrasonography studies limited to the cruro
      popliteal level. The difference came from the "other venous thrombi" and "distal
      deep venous thrombi" discovered by exploring the superficial and muscular
      networks and the calves. This study demonstrates the contribution of duplex
      ultrasonography to the diagnostic strategy for pulmonary embolism.

PMID- 11240527
TI  - [Investigation of peripheral vascular bed in critical lower limb ischemia:
      comparative study between arteriography and magnetic resonance angiography].
AB  - OBJECTIVES: To determine the precise role of arteriography and contrast-enhanced
      magnetic resonance angiography (MRA) to evaluate the peripheral vascular bed in
      critical ischemia of the lower limbs in candidates for distal vascularization.
      MATERIAL AND METHODS: Fifteen patients (mean age 66 +/- 18 years) underwent MRA
      and arteriography. In all, 23 lower limbs were studied by non-selective
      arteriography with aortic injection (n=12) or selective arteriography with
      iliofemoral injection (n=11). RESULTS: The strength of agreement between MRA and
      selective arteriography was good (k=0.75) for analysis of leg arteries. MRA was
      better than non-selective arteriography (p<0.035) to evaluate artery patency. In
      our study, only MRA improved the treatment decision. CONCLUSION: In patients
      requiring an assessment of the peripheral vascular bed before distal
      revascularization, contrast-enhanced MRA can be the first exam. In case of an
      inadequate MRA, only selective arteriography needs to be performed.

PMID- 11240528
TI  - [Management of venous leg ulcer by French physicians, diversity and related
      costs: a prospective medicoeconomic observational study].
AB  - OBJECTIVES: The purpose of this study was to better ascertain how French
      physicians manage venous ulcers of the lower limbs. We explored the various
      therapeutic approaches used and their respective costs. Particular attention was
      focused on dressing prescriptions. MATERIAL AND METHODS: A prospective
      medicoeconomic study was conducted. Eight hundred general practitioners and
      specialists throughout France were included and followed two patients each, one
      with a "new ulcer" (less than two weeks) and another with a "longstanding ulcer"
      (more than six weeks). Patients were followed to healing or for up to six months.
      An observation chart was completed at each visit. Data collected were
      characteristics of the ulcer at inclusion, assessment of the clinical course, and
      the nature and the volume of medical care prescribed. Corresponding costs (total
      cost for the society) were calculated on the basis of 1996 public prices for
      drugs and the French national health insurance quotations for ambulatory care.
      For hospital care, cost was calculated from the cost of stay for homogeneous
      patient groups. RESULTS: Files established for 1,098 patients by 652 physicians
      could be assessed. Elderly female patients predominated in this population (mean
      age 72 years, 74% women). The length of the ulcer at inclusion was significantly
      correlated with its duration: 2.82 cm for new ulcers (52.6% of the cases) versus
      5.03 cm for longstanding ulcers (47.3%). The mean number of consultations for all
      patients was 4.8 over a 29-day period. Mean cost resulting from these
      consultations was 5,827 FF per patient: 48% for care, 33 for drugs, 16% for
      hospitalizations, and 3% for work lay-off ). Cure was achieved in 77% of the
      cases within a mean delay of 3 months. Older ulcer was significantly associated
      with longer treatment (117 days for longstanding ulcers versus 80 days for new
      ulcers), lower cure rate (67% versus 86%) and higher cost (7 078 FF versus 4 669
      FF). Dividing care methods between those using cleaning with compression or not
      showed that compression was prescribed in 76% of the cases at the inclusion
      consultation. This predominance of compression therapy did not preclude use of a
      variety of other therapeutic methods depending on the clinical and demographic
      situation of the patient. Cost varied accordingly with a mean ranging from 3 160
      FF to 6 697 FF depending on the therapeutic attitude. The study also focused on
      the type and amount of dressings used. Dressings were prescribed for 56 patients
      in this series. It can be hypothesized that these patients already had dressings.
      Different indicators show that the absence of prescriptions for dressings
      concerned less severe and less costly ulcers (4 130 FF versus 5 918 FF for those
      with dressing prescriptions). Among the 1 042 patients for whom dressings were
      prescribed, 35% were for occlusive dressings, 29% for ointment dressings and also
      24% for both occlusive and ointment dressings. The type was not specified in 55%
      of the cases. Mean cost for these different categories ranged from 4 921 to 7 019
      FF.

PMID- 11240529
TI  - [Post-irradiation axillo-subclavian arteriopathy: surgical revascularization].
AB  - Post-irradiation axillo-subclavian arteriopathy can develop 6 months to 20 years
      after radiotherapy. Incidence estimated from duplex scan screening is about 30%,
      half of the cases having no hemodynamic significance. In our experience,
      asymptomatic lesions are the most common. Nevertheless, we have observed since
      1978, 38 symptomatic patients including 23 with either acute ischemia (8
      patients), or chronic ischemia (15 patients) requiring revascularization. We used
      an endovascular approach in 8 and open surgery in 15. A bypass graft was
      performed in 13 patients, using a vein (8 patients) rather than a prosthesis (5
      patients), implanted in healthy territory, proximally or in the common carotid
      (11 patients) or the proximal subclavian (2 patients), and distally in the
      axillary artery (5 patients) or the brachial artery (8 patients). One venous
      bypass became occluded postoperatively. The other bypasses remained patent during
      follow-up of over 10 years. There of the five prosthetic bypassess gradually
      failed without recurrence of critical ischemia. Other revascularization
      procedures included endarterectomy and thrombectomy. In the long term, functional
      prognosis mainly depended on the frequently associated involvement of the plexus
      in the post-irradiation changes, which, together with the revascularization
      procedure, also required neurolysis in 11 patients, two omental covers and a free
      musculocutaneous transfer in 9 patients.

PMID- 11240530
TI  - [Can minimal arterial aggressions using non-penetrating mechanical clip suture
      prevent myo-intimal hyperplasia? Preliminary results].
AB  - SUBJECT: Vascular anastomosis is still associated with a significant rate of
      early (stenosis, thrombosis) and delayed (intimal hyperplasia) complications.
      Even though suture closure remains the most widespread standard procedure, many
      mechanical systems have been developed mostly using non penetrating clips, aiming
      to make the suture easier, to reduce the operating time and to reduce the
      scarring process of the arterial wall. We investigated the usefulness of non
      penetrating titanium Vascular Closure Staple (VCS) developed for peripheral blood
      vessels anastomosis, in a study on 20 rabbits with the small VCS system. MATERIAL
      AND METHODS: On 20 rabbits, 9 of the aortic sutures were done with VCS clips and
      11 were done by standard closure. RESULTS: We found a significant improvement in
      the operating time of the closure (9 +/- 2 minutes versus 14 +/- 4 minutes),
      early and delayed (10 weeks) patency and the respect of the aorta diameter (0.248
      +/- 0.01 centimetres versus 0.246 +/- 0.039 centimetres) and loss of surface
      (40.3 +/- 5.59% versus 45.6 +/- 6.34%). The main improvement is the reduced
      intimal hyperplasia (0.128 +/- 0.05 millimetres versus 0.198 +/- 0.032
      millimetres. P=0.012). CONCLUSION: Arterial closure can be performed more rapidly
      with VCS clips than with suture closure, and with a marked reduced reaction of
      intimal hyperplasia. With those elements it is necessary to continue the
      experimental studies and to evaluate the VCS sutures at mean and long term.

PMID- 11240531
TI  - [Aneurysm of a persistent sciatic artery: five case reports].
AB  - We report five cases of a persistent sciatic artery. The lesion was unilateral in
      all cases. Four patients were treated by exclusion of the aneurysm with ligature
      of the internal iliac artery with an associated femoropopliteal bypass in two.
      Surgical treatment was declined by one patient. We discuss the embryology,
      pathology, clinical aspects and surgical procedures involved.

PMID- 11240532
TI  - [Intimal muscular fibrodysplasia responsible for an ischemic gastric ulcer in a
      patient with a von Recklinghausen's disease: a case report].
AB  - A 78 year-old woman, suffering from a von Recklinghausen's disease sought medical
      assistance for hematemesis with anemia. This patient had previously experienced
      an amputation of the right arm for gangrene. Gastric fibroscopy unveiled a deep
      chronic ulcus developed in the antrum, highly suspect of malignancy. Multiple
      biopsies of the ulcer showed mainly interstitial gastritis. The persistence of
      the hematemesis imposed a subtotal gastrectomy. Pathological examination of the
      operative specimen evidenced an ischemic ulcer caused by arterial intimal
      muscular fibrodysplasia with associated neurofibromatosis in the neighboring sub
      mucosal layer. This case report highlights the frequent association of
      phacomatosis especially von Recklinghausen's disease, with vascular lesions whose
      clinical expression mainly depends on the involved vascular area.

PMID- 11240533
TI  - [In vitro assessment of combining osteogenic cells with macroporous calcium
      phosphate ceramics].
AB  - PURPOSE OF THE STUDY: Bone grafts or bone substitutes are required to fill bone
      defects resulting from trauma or surgical resection of tumors. Calcium-phosphate
      ceramics are synthetic bone substitutes which promote new bone formation by
      osteoconduction. These ceramics possess osteoconductive properties but have no
      intrinsic osteoinductive capacity. They are unable to induce new bone formation
      in extraossesous sites. One solution to develop bone substitutes with osteogenic
      properties would be to associate biomaterials with osteoprogenitors. MATERIALS
      AND METHODS: We studied the in vitro osteogenic potential of human bone-marrow
      cells cultured on macroporous calcium phosphate (CaP) ceramic, examining stromal
      cell proliferation and differentiation. Osteogenic differentiation was evaluated
      in terms of alkaline phosphatase activity and immunological characterization of
      the extracellular fibrillar matrix formed by these cells. The specimens were
      examined by scanning and transmission electron microscopy. RESULTS: Human bone
      marrow cells proliferated on CaP ceramic. The proliferating bone-marrow cells
      expressed an osteoblastic phenotype as shown by alkaline phosphatase activity and
      synthesis in ceramic pores of an extracellular matrix composed of fibronectin,
      osteocalcin and collagen I. In addition, numerous microcrystals of apatite
      precipitated on the fibrillar matrix, producing a mineralized fibrillar network
      within the ceramic. CONCLUSION: This study demonstrates that human bone-marrow
      cells cultured on macroporous CaP ceramic do not lose their osteoblastic
      phenotype even after 21 days of culture, and that they can induce osteogenesis in
      a CaP ceramic in vitro. This type of new "hybrid material" appears promising for
      the future.

PMID- 11240534
TI  - [Computer-assisted knee arthroplasty: comparison with a conventional procedure.
      Results of 50 cases in a prospective randomized study].
AB  - PURPOSE OF THE STUDY: The aim of this work was to compare the radiographic
      findings after two techniques for total knee arthroplasty, one using a computer
      assisted approach and the other a conventional approach. MATERIAL AND METHODS:
      Between January 1998 and April 1999, we conducted a prospective study randomizing
      25 patients for conventional surgery (group A) and 25 for computer-assisted
      surgery (group B). All patients volunteered to participate in this study and gave
      their written informed consent. There were 35 women and 15 men, mean age 69.5
      years (range 47-85). The two groups were comparable for age, gender, height,
      weight, orthopedic history, etiology and preoperative mobility. The preoperative
      hip-knee angle (HKA) was also comparable between the two groups. Mean HKA was 175
      degrees, i.e. 5 degrees varus (range 162 degrees (18 degrees varus) to 210
      degrees (30 degrees valgus)). Genu varum was found in 80 p. 100 of the patients
      in group A and in 76 p. 100 in group B, genu valgum in 16 p. 100 in group A and
      24 p. 100 in group B. The same operator performed all the procedures) with the
      same type ok prosthesis for all patients. The goal of the operation was to
      position the prosthesis to produce an HKA of 180 +/- 3 degrees, a femoral angle
      of 90 degrees (from the mechanical axis), a tibial angle of 90 degrees and a
      posterior tibial slope of 0 degrees (tibial plateau at 90 degrees to the lateral
      tibial axis). Statview 5 PC was used for the statistical analysis. Comparisons
      between groups were made with the Student's t test to compare means when the
      validity conditions were met. RESULTS: The patients were reviewed by two
      surgeons, independently of the operator and the designers of the computer
      assistance program. Mean duration of the procedure was longer in group B (102 mn
      versus 70 mn, p<0.001). There was no statistically significant difference in mean
      postoperative bleeding (group A=380 cc, group B=480 cc). The postoperative HKA
      was 181.2 +/- 2.72 degrees in group A and 179.04 +/- 2.53 degrees in group B (p >
      0.05). The HKA was between 177 degrees and 183 degrees in 75 p. 100 of the
      patients in group A and in 84 p. 100 of those in group B. Implantation of the
      femoral component showed a mean angle of 91.12 +/- 2.07 degrees in group A and
      89.56 +/- 1.61 degrees in group B (p=0.048). The mean tibial angle was 90.167 +/-
      1.61 degrees in group A and 89.5 +/- 1.34 degrees in group B (p=0.11). On the
      lateral view, the femoral component was at 90 degrees to the mechanical axis in
      16/21 patients in group B. These data were missing in group A. The posterior
      tibial slope was 90.76 +/- 2.19 degrees in group A and 89.44 +/- 2.14 in group B
      (p=0.18). CONCLUSION: Computer-assisted surgery for total knee arthroplasty was
      found to provide remarkably reliable results. Once the "growing pains" of this
      new material have been mastered, all surgeons should be able to expect an
      improvement in the positioning of prosthetic implantations.

PMID- 11240535
TI  - [A prospective randomized study of wound drainage versus non-drainage in primary
      total hip or knee arthroplasty].
AB  - PURPOSE OF THE STUDY: Drainage of the operative wound following total hip or knee
      replacement (THR, TKR) is usually performed to avoid hematoma formation. A
      certain amount of blood is lost through the drain. The necessity of wound
      drainage has been questioned, with a view towards blood saving, although most
      surgeons have not abandoned drainage for fear of local complications. A
      prospective randomized study was undertaken to compare drainage and non-drainage
      following THR/TKR in terms of blood-saving and local complications. MATERIAL AND
      METHODS: A total of 256 patients undergoing primary THR (152) or TKR (104) were
      randomly allocated to undergo either suction drainage or no drainage of the
      wound: there were 76 drained and 76 non-drained THR's, 52 drained and 52 non
      drained TKR's. Blood loss was calculated in each patient from the postoperative
      drop in hematocrit values; the amounts of blood lost intra-operatively and in the
      drain were also recorded, as was the number of blood units transfused in each
      patient. Swelling, hip or knee range of motion and wound healing were monitored
      over the first 6 weeks after operation, and any local or systemic complication
      was recorded. RESULTS: No significant difference was noted between drained and
      non-drained THR's/TKR's regarding swelling, recovery of hip or knee motion, wound
      healing, other local or systemic complications. Following THR, no significant
      difference was noted between calculated blood losses or transfusion requirements
      in drained versus non-drained patients. Patients with drains lost on average 1
      942 ml of blood versus 1 766 ml for non-drained patients; they received on
      average 1.18 units of transfused blood versus 1.32 units for patients without
      drains. The differences are not significant. Following TKR, total blood loss was
      significantly higher in non-drained than in drained patients (1 983 ml versus 1
      590 ml) and the amount of blood transfused was also significantly higher in non
      drained patients (0.98 unit versus 0.54 unit). CONCLUSION: Following primary hip
      or knee arthroplasty, the use of wound drainage did not lead to increased blood
      loss, and non-drainage did not lead to significant wound healing problems but did
      not reduce blood loss and transfusion requirements. It was even associated,
      following TKR, with greater blood loss and transfusion. Such data may therefore
      be used to support drainage as well as non-drainage following THR or TKR.
      Avoiding drainage may be interesting in terms of cost, but the benefit is
      marginal; it also eliminates one possible source of retrograde wound infection.
      Systematic wound drainage following THR or TKR is essentially a tradition. This
      study shows that it can safely be dispensed with in a number of cases.

PMID- 11240537
TI  - [Dual x-ray absorptiometry assessment of bone density of the proximal tibia in
      advanced-stage degenerative disease of the knee].
AB  - PURPOSE OF THE STUDY: Axial deformity secondary to degenerative joint disease of
      the knee can modify stress forces. Certain studies have reported an inversely
      proportional relationship between degenerative disease and osteoporosis. The aim
      of this prospective study was to quantify the horizontal linear distribution of
      bone density using dual x-ray absorptiometry (DXA) of the proximal tibia as a
      function of the femoral neck bone density in patients with knee osteoarthritis.
      MATERIAL AND METHODS: Between September 1996 and March 1998, 90 cases of primary
      degenerative joint disease of the knee were programmed for total knee
      arthroplasty. Prior to the procedure, the patients were assessed clinically and
      radiologically according to the International Knee Society (IKS) criteria. The
      mechanical femorotibial angle was measured in all patients and the varus angles
      were recorded. Most of the patients were women (65 p. 100) with a mean age of 70
      +/- 5 years. Valgus knees were excluded from this series. The mean mechanical
      femorotibial angle was 172 +/- 5 degrees. Fifteen patients had a normal axis (16
      p. 100), 32 had a varus measuring 4 degrees to 10 degrees (35 p. 100) and 43 had
      a varus measuring 10 degrees or more (48 p. 100). The overall varus distance was
      6.4 +/- 2 cm. All patients had two DXA explorations: femoral neck to determine
      the bone status according to the WHO criteria (normal, osteopenia, osteoporosis),
      knee to determine the linear distribution of bone density of the proximal tibia.
      A 7 mm high band including 7 regions of interest covering the width of the tibia
      were explored in the area where the tibial cut was to be made. These 7 regions of
      interest were: R1, R2 under the lateral compartment, R6, R7 under the medial
      compartment, and R3, R4, R5 on either side of the tibial spines. The level of
      significance was set at 5 p. 100. RESULTS: The mean Z score (0.54 +/- 1) in the
      90 patients showed a symmetrical distribution. These patients were representative
      of their age range. Their T score was - 1.40 +/- 1 (m +/- SD) and most had
      osteopenia (54 p. 100) according to the WHO criteria, although 16 p. 100 had
      osteoporosis. Mean bone density of the knee was 0.898 +/- 0.163 g/cm(3) and was
      correlated with that of the femoral neck (r=0.61, p=0.001). There were
      significant correlations between the differences in the bone densities of the
      knee compartments (R6-R2, R7-R1) and the mechanical femorotibial angle [(r=0.39,
      p=0.0001); (r=0.52, p=0.001)]. Irrespective of the overall bone density, there
      was a strong medial compartment overloading, which correlated with the degree of
      varus deformation. CONCLUSION: DXA assessment of bone mineral density of the
      proximal tibia is a simple, reliable, precise and reproducible method. The
      distribution of bone density in the degenerative knee depends on the degree of
      deformation. The average level depends on the subject's general state of
      mineralization. Osteoporosis does not protect against degeneration of the knee
      joint since 16 p. 100 of our patients had osteoporosis according to the WHO
      criteria.

PMID- 11240536
TI  - [Mid-term behavior of the bone fixation in non-cemented Miller-Galante 1 total
      knee arthroplasty].
AB  - PURPOSE OF THE STUDY: This retrospective work was conducted to analyze the
      quality of the bone-implant interface at mid-term in 45 cases treated with a non
      cemented Miller-Galante 1 total knee arthroplasty. MATERIAL AND METHODS: All the
      protheses reviewed were implanted without cement. A patellar implant was cemented
      in 31.1 p. 100 of the cases. Female sex predominated in this series (77.5 p. 100)
      and the mean age at operation was 67 +/- 6 years. Pre- and postoperative
      assessment was based on the HSS score. Mean follow-up was 8.3 years (range 7-11
      years). We used the method advocated by the International Knee Society to analyze
      lucent lines on tibial and femoral implants. Non-parametric tests were used for
      the statistical analysis with a significance level set at 5 p. 100. RESULTS: The
      mean HSS score rose from 55 +/- 12 preoperatively to 80 +/- 13 postoperatively,
      with 62.2 p. 100 good or excellent results at last follow-up. One re-operation
      was required for aseptic loosening. The femoral implant presented a lucent line
      in 24.4 p. 100 of the cases at the first follow-up examination only. The tibial
      implant presented an anterior lucent line at the second follow-up examination
      then a medial line at the last follow-up in 22.2 p. 100 and 26.6 p. 100 of the
      cases respectively. Presence of a lucent line (tibial or femoral) on at least one
      view was significantly correlated with activity (p=0.01) and tibial slope
      (p=0.0087). DISCUSSION: The disappearance of the lucent lines seen on the femoral
      component at the second follow-up examination was the expression of its secondary
      integration. Inversely, we observed an evolution in the lines observed on the
      tibia. This was probably the result of posterolateral impaction and anteromedial
      ascension micromovements of the tibial component. An excessive tibial slope was
      statistically related to development of lucent lines. It increased tibial
      translation on weight bearing and probably induced an abnormal alteration of the
      polyethylene. We did not observe any case of massive osteolysis of the tibial
      metaphysis as described in the literature for non-cemented knee arthroplasties.
      The screws of the Miller-Galante 1 prosthesis do not protrude from the tibial
      implant (which would risk generating polyethylene debris) and the pieces used
      (screws and implants) are all made of the same metal. CONCLUSION: The quality of
      primary fixation of the non-cemented Miller-Galante 1 tibial implant was not
      totally satisfactory at mid-term. Inversely, simple impaction of the femoral
      component was sufficient to ensure stable positioning.

PMID- 11240538
TI  - [Long-term outcome after Ilizarov corrective fixation for severe foot deformity].
AB  - PURPOSE OF THE STUDY: Much work has focused on the short-term outcome after
      external fixation with the Ilizarov apparatus for treatment of severe recurrent
      or neglected foot deformity. No series has provided sufficient follow-up to allow
      an analysis of long-term stabilization. MATERIAL AND METHODS: We reviewed a
      series of 17 patients (21 feet) treated with the Ilizarov apparatus between 1988
      and 1998 and reexamined after a mean 6-year follow-up. We assessed the risk of
      degradation of the initial result and quantified the need for secondary
      arthrodesis surgery. This series included 18 congenital clubfeet and 3 cases of
      acquired talipes equinus. Mean patient age was 15 years. RESULTS: Pain,
      morphology, weight bearing attitude and quality of shoe fit were assessed.
      Results at treatment end were very good in 16 cases, good in 4 and poor in 1. Two
      early recurrences required arthrodesis. At last follow-up, results were very good
      in 17 cases, good in 3, and poor in 1 (late recurrence with arthrogryposis).
      DISCUSSION: With 3 recurrences among 21 cases, results were maintained well over
      time in this series. Most of the recurrences were observed during the first year
      and never completely reproduced the initial deformation. In 2 out of 3 cases, the
      recurrence occurred on a secondary talipes equinovarus. Age was not a risk factor
      (only 2 feet have not reached maturity to date). The lack of over-correction at
      treatment end is a factor predictive of poor outcome. CONCLUSION: Long-term
      outcome demonstrated the stability of the results and the absence of severe
      complications and foot shortening, emphasizing the important contribution of
      Ilizarov fixation for severe foot deformity.

PMID- 11240539
TI  - [Interpositioned metallic prosthesis for hallux rigidus: review of 42 cases with
      a metatarsophalangeal prosthesis].
AB  - PURPOSE OF THE STUDY: We report outcome at a mean 4.8 years follow-up in 42
      patients with hallux rigidus treated by metatarsophalangeal interposition thin
      prosthesis flat concave with a lateral capsular fixation. MATERIALS AND METHODS:
      The 42 patients were treated from 1987 to 1997. Sixtine prostheses were implanted
      for osteoarthritis was grade I (n=2), grade II (n=28), and grade III (n=12).
      Groulier's clinical criteria and Regnauld's radiologic criteria were used to
      assess outcome. RESULTS: We observed 22 very good, 12 good, 4 fair, and 4 poor
      results. There was no significant modification in the forefoot morphology.
      DISCUSSION: The Sixtine prosthesis provided a global improvement in pain and
      motion though there was an important difference between patients with grade I and
      grade II osteoarthritis, who experienced major improvement, and those with grade
      III disease. A good overall result requires proper prosthetic centering.
      Subluxation or translation does not appear to be compatible with good results.
      Among 3 cases with overt dislocation, 1 recovered an acceptable articular space
      with a good overall result. Two poor results and 3 fair results were observed in
      patients with condensation of the phalangeal base. These bone condensations
      appeared in postoperative Egyptian feet. The Sixtine prosthesis may protect the
      interphalangeal articular space of the great toe, avoiding damage and rearward
      displacement of sesamoid bones. It ensures primary stability and may be left in
      place. CONCLUSION: We found that the Sixtine prosthesis is best indicated in
      hallux rigidus patients with grade II osteoarthritis.

PMID- 11240540
TI  - [Videoscopic retropleural and retroperitoneal approach to the thoracolumbar
      junction of the spine].
AB  - PURPOSE OF THE STUDY: A minimally invasive anterior approach has been developed
      for the thoracolumbar junction of the spine. The aim of this study was to
      evaluate the possibilities of videoscopic treatment of fractures and malunions of
      the thoracolumbar junction and to report the first results obtained with this
      technique. MATERIAL AND METHODS: Video-assisted surgery was performed in eleven
      patients using costal resection and a retropleural and retroperitoneal approach.
      Anterior arthrodesis was performed in all cases, four with anterior
      instrumentation. The indications were trauma for six patients and malunion for
      five. RESULTS: Mean follow-up was 17.4 months. For malunion patients, the mean
      angular gain was 22.4 degrees. Radiological anterior fusion was achieved in all
      cases except one. The mean angular loss was 5.7 degrees. DISCUSSION: The surgeon
      can control the procedures by direct vision, while the assistant follows the
      operation on the video display screen. The upper par of L1 can be reached via a
      supradiaphragmatic retropleural approach, while a larger exposure is possible if
      the insertions of the diaphragm are released and the retroperitoneal space is
      opened. The crus does not have to be sectioned to expose the lateral part of the
      thoracolumbar vertebrae. Possible complications are similar to those which can be
      observed with open procedures. CONCLUSION: The videoscopic approach enables the
      exposure of throacolumbar junction with a smaller parietal lesion than with open
      procedures. It enables arthrodesis procedures with corporectomay, angular
      correction and anterior osteosynthesis.

PMID- 11240541
TI  - [An unusual shoulder stiffness: metastasis in the infraspinatus muscle as the
      first clinical manifestation of lung carcinoma].
AB  - PURPOSE OF THE STUDY: Malignant metastases are rarely located in skeletal
      muscles. We report a case of lung adenocarcinoma disclosed by metastatic
      dissemination to the infraspinatus muscle. CASE REPORT: A 66-year-old man
      consulted for a painful stiff right shoulder. Pain had developed progressively
      and did not respond to class 2 antalgesics. There was a complete loss of passive
      and active medial rotation while the other shoulder amplitudes were normal. A
      discrete tumefaction was palpated in the infraspinatus fossa. Magnetic resonance
      imaging alone was able to evidence an intramuscular tumoral formation within the
      infraspinatus. Surgical excision led to the diagnosis of metastatic
      adenocarcinoma of the lung and provided rapid pain relief. Nearly normal medial
      rotation amplitude was recovered. The patient died at 10 months from
      complications related to the lung adenocarcinoma. DISCUSSION: This is the first
      report of metastatic lung carcinoma located in the infraspinatus muscle. The
      clinical presentation was very exceptional, no similar cases being reported in
      the literature. In bloc surgical resection appears to be the best therapeutic
      approach, allowing positive diagnosis and relief of pain and stiffness.

PMID- 11240542
TI  - [Malignant fibrous histiocytoma of bone 20 years after femoral fracture treated
      by plate-screw fixation: analysis of corrosion products and their role in
      malignancy].
AB  - We report a case of malignant fibrous histiocytoma of the bone that developed 20
      years after a femoral fracture treated by plate-screw fixation. Similar cases
      reported over the past fifteen years in the literature suggest the possible
      mechanisms of sarcomatous degeneration. The possible carcinogenic effect of
      corrosion products is emphasized. Dispersion energy spectrometry of intracellular
      particles on the periphery and at the center of the tumor demonstrated the
      presence of chromium, iron and nickel at different concentrations. The
      association with other elements clearly demonstrates that the corrosion products
      were metabolized. The presence of metallic components in tumoral cells suggests a
      possible relationship between metallic implants and malignancy. These
      observations emphasize the importance of creating a national, or even
      international, registry of malignant tumors that develop in contact with metallic
      implants in order to search for a possible cause and effect relationship.

PMID- 11240544
TI  - [What can be expected from brain MRI in early-stage multiple sclerosis?].

PMID- 11240545
TI  - [Benign intracranial hypertension].
AB  - Benign intracranial hypertension (BIH) is characterized by an elevation of the
      intracranial pressure not associated with an intracranial process or
      hydrocephaly, and with normal cerebrospinal fluid (CSF) contents. The elevation
      of the intracranial pressure is isolated; therefore, diseases such as cerebral
      venous thrombosis or dural fistulas should not be considered as etiologies of
      BIH. The exact definition of BIH remains debated, and other terms such as
      "pseudotumor cerebri" or "idiopathic intracranial hypertension" are often used in
      the literature. Although we agree that BIH is usually not a so benign disease, we
      suggest that BIH is still the most appropriate term to describe this entity which
      should be classified as "secondary BIH" or "idiopathic BIH" depending on whether
      there are precipitating factors for the development of BIH or not. We also
      propose new diagnostic criteria emphasizing the need for investigations for the
      diagnostic of secondary and idiopathic BIH. The management of patients with BIH
      depends mainly on the presence and severity of ocular symptoms and signs on which
      the prognostic of the disease is based. Repeated lumbar punctures associated with
      acetazolamide and weight loss are usually efficient enough. However a surgical
      treatment (optic nerve sheath fenestration or lumboperitoneal shunt) is required
      when appropriate medical management does not prevent progressive alteration of
      vision (visual loss or visual field defect), or when the patients complains of
      severe, refractory headaches. Careful follow-up with repeated formal visual field
      testing may help preventing a devastating visual loss in these patients.

PMID- 11240546
TI  - [Study with localized proton magnetic resonance spectroscopy of 31 multiple
      sclerosis lesions: correlations with clinical and MRI features].
AB  - We have analyzed with localized proton magnetic resonance spectroscopy (MRS) 31
      lesions in 28 patients with multiple sclerosis (MS). The course of the disease
      was either relapsing remitting, secondary progressive, or primary progressive.
      Four patients had an isolated neurological syndrome suggestive of MS. The
      decrease in the NAA/Cre ratio and the raise of the Cho/Cre ratio were more
      pronounced in patients with an acute isolated neurological syndrome, suggesting
      the predominance of an inflammatory process, and the presence of an axonal
      dysfunction in the initial course of the lesion. The NAA/Cre ratio was negatively
      correlated with clinical disability and thus could be used as an index of disease
      activity. Patients with a secondary progressive course exhibited a significant
      increase in the Myo/Cre ratio compared to those with a relapsing remitting
      course. Thus, there may be an association between the evolution towards a
      progressive disease and axonal loss or the development of gliosis. The isointense
      lesions to the cerebrospinal fluid on MRI T1 weighted sequences were
      characterized by a sharp raise in the Cho/Cre ratio suggesting demyelination
      and/or intense inflammation. Gadolinium enhanced lesions were not characterized
      by a specific neurochemical profile.

PMID- 11240547
TI  - [Neurological comorbidity in parkinsonism].
AB  - We studied the neurological comorbidity of parkinsonism in 368 consecutive
      patients from the Lausanne Movement Disorders Registry. Only 6 patients had no
      neurological comorbidity. We found that 23p.100 of our patients had ischemic
      strokes, especially large vessel strokes, i.e three times more than in an age
      matched control study performed in a recent survey in our country, which is a new
      finding in contradiction with previous reports mentioning that Parkinson's
      disease may be a protective factor against stroke. This finding opens new
      directions for further studies concerning some shared mechanisms in both diseases
      associated with age. Predominantly tremulous parkinsonism (46p.100) and
      progressive supranuclear palsy patients (PSP) (40p.100) had the highest
      prevalence of cerebrovascular disease of all subgroups of parkinsonism,
      especially lacunar infarcts, which is in accord with a higher frequency of
      hypertension in these subgroups according to a recent study of ours. Transient
      ischemic attacks or hemorrhages were not more frequent than in the general
      population. We did not find a higher frequency of head trauma except for
      Parkinson's disease, but a trend for a higher frequency of headache and migraine.
      Brain tumors were more frequent in Parkinson's disease and hydrocephalus and
      radiculopathies in parkinsonism in general when compared to age-matched
      populations from the literature. Polyneuropathies were more frequently observed
      in familial parkinsonism only, but myopathies and cranial neuropathies were not
      more frequent in our patients. Epilepsy was significantly less frequent in
      parkinsonism, especially in Parkinson's disease, infectious diseases of the
      nervous system were rarely encountered, and restless legs syndrome was
      surprisingly not more frequent than in a normal population. Dementia was
      associated in 20p.100, but multiple sclerosis is noticeably absent.

PMID- 11240548
TI  - [Neurological manifestation of infectious endocarditis: 14 cases].
AB  - Fourteen cases of infective endocarditis revealed by neurological manifestations
      are reported: 8 strokes (one transient ischemic attack, one regressing and 6
      completed strokes), 2 intracranial hematomas (one due to ruptured mycotic
      aneurysm), 2 toxic encephalopathies, one grand mal seizure, one suppurative
      meningitis. Most of them were native valve endocarditis, and streptococcus was
      the most frequently responsible bacteria. The outcome was characterized by a high
      mortality (6 cases) and morbidity (4 cases). This emphasizes the usefulness of
      preventing antibiotherapy in patients with known predisposing factors and the
      necessity for these patients to be admitted in neurological intensive care units.

PMID- 11240549
TI  - [Neuropsychological disorders after bithalamic infarct caused by deep venous
      thrombosis].
AB  - We report a case of deep cerebral venous thrombosis with bithalamic infarction
      that led to neuropsychological disorders including left side visuospatial
      neglect, aphasia and amnesia, as well as frontal and intellectual disorders.
      After a six month course, the patient showed only slight intellectual deficit and
      mild anterograde amnesia. Deep cerebral venous thrombosis is uncommon and
      prognosis is poor. Reports in the literature illustrate the neuropsychological
      disturbances they provoke but provide little analyzable data. The positive
      progress in our case demonstrates that bithalamic lesions of venous origin can
      have a good prognosis.

PMID- 11240550
TI  - [Recurrent syncope and Chiari malformation].
AB  - Downward herniation of the cerebellar tonsils through the foramen magnum (Chiari
      I malformation) is usually revealed by head and neck pain, often associated with
      brain-stem or spinal cord disturbances. Syncopes are rarely reported and may be
      difficult to link to their cause when they occur alone. We report two cases with
      brief and repetitive syncopes revealing a Chiari I malformation. These
      manifestations may be attributed to transient compression of brain stem or
      vascular structures at the craniocervical junction, triggered by intracranial
      pressure increase, as they disappear after posterior fossa decompression.

PMID- 11240551
TI  - [Electrophysiologic study of 10 cases of Miller Fisher syndrome].
AB  - The association of ophthalmoplegia, ataxia and areflexia was described by Miller
      Fisher in 1956. It is postulated as a variant of the Guillain Barre syndrome. We
      report 10 Miller Fisher syndrome patients admitted in an intensive care unit
      between June 1990 and February 1999 who were selected according to clinical
      criteria of Ropper and Wijdicks. All patients had motor and sensory nerve
      conduction studies and electromyography, nine had visual and brainstem auditory
      evoked potentials and two had short latency somatosensory evoked potentials.
      Peripheral neuropathy was found in all patients. All had sensory nerve changes
      and some were severe. Motor nerve conduction abnormalities were observed in 7
      only cases with moderate increase of F latency in 3 cases and compound muscle
      action potential reduction in 3 other cases. In the last case, motor conduction
      abnormalities was more severe, characterized by conduction velocity slowing in
      both distal and proximal sites and by temporal dispersion of action potentials.
      All brainstem auditory evoked studies were normal. In 4 patients, MRI studies
      were normal. These data support that brainstem is preserved in MFS. Only one
      patient had visual evoked potential abnormalities. Optic neuropathy is debated in
      Miller Fisher and in Guillain Barre syndrome. As a conclusion, in MFS peripheral
      neuropathy is always present with severe sensitive changes and moderate motor
      changes (This is different as compared to Guillain Barre syndrome according to
      electrophysiological data). We did not find involvement of brainstem in our
      patients with Miller Fisher syndrome.

PMID- 11240552
TI  - [Kjellin syndrome].
AB  - A previously healthy 30-year-old woman who had cognitive impairment since
      childhood suddenly developed progressive spastic paraparesis. Visual impairment
      and characteristic retinal macular spots supported the diagnosis of Kjellin
      syndrome. This disease, probably transmitted by autosomal recessive inheritance,
      is seldom observed in clinical practice. We describe the characteristics of
      Kjellin syndrome and the differential diagnosis, including other macular changes
      associated with spastic paraparesis.

PMID- 11240553
TI  - [Postinfectious hemicerebellitis].
AB  - The clinical signs of cerebellitis are usually bilateral and symmetrical. We
      report the case of a 9-year-old girl who presented with acute hemiataxia and
      flaccid hemiparesis associated with a lesion in the ipsilateral cerebellar cortex
      two weeks after a viral upper respiratory tract infection. The clinical outcome
      was good without treatment. Imaging follow-up showed hemiatrophy of the
      cerebellar cortex.

PMID- 11240554
TI  - [Legal aspects of temporal lobe epilepsy in prisoners].
AB  - The last report of the french Direction Generale de La Sante noted that epilepsy
      is twice more common in inmates than in the French population at large for the
      same range of age. Temporal lobe epilepsy is well known to give rise to
      aggressive behaviour and to psychotic syndromes. The development in prison of
      auto- or hetero aggressive behaviours has also been observed. We report on a 24
      years-old male who was incarcerated for violence and robbery. He worked as a
      plumber and had no medical history except hepatitis C and use of IV drugs.
      Temporal lobe epilepsy was diagnosed because of auditory hallucinations.
      Consequences of this behaviour are discussed. Although it can be difficult to
      link the behavioural disorder to the disease, we would like to suggest that his
      delinquency could have been prevented by appropriate medical care before
      incarceration.

PMID- 11240555
TI  - [Peripheral motor neurone dysfunction: unique manifestation of syphilis].

PMID- 11240556
TI  - [Epilepsy, bi-occipital calcifications and celiac disease].

PMID- 11240557
TI  - [Wilson's disease].

PMID- 11240558
TI  - [Practical recommendations for MRI in MS].

PMID- 11240559
TI  - [Comments on the recommendations for MRI in MS (Tourbah et al.)].

PMID- 11240560
TI  - Creutzfeldt-Jakob disease segregating in a three generation Danish family.
AB  - A three generation family is presented in which rapidly progressive, early-onset
      Creutzfeldt-Jakob disease without typical EEG changes segregates as an autosomal
      dominant disease. An aspartic acid to asparagine mutation at codon 178 of the
      prion gene, PRNP, co-segregates with the disease. As expected, the disease allele
      also carries the valine codon of the polymorphic valine/methionine codon 129 of
      the gene. In family members homozygous for this valine codon the disease was more
      rapidly progressive than in a heterozygous family member, who had a variant
      clinical phenotype. Definite neuropathological diagnosis required prion staining
      with specific antibodies.

PMID- 11240561
TI  - Early prediction of aphasia outcome in left basal ganglia hemorrhage.
AB  - OBJECTIVES: The independent predictors of aphasia outcome for patients with left
      basal ganglia hemorrhage were evaluated. PATIENTS AND METHODS: We included 140
      patients of 1,036 patients with spontaneous intracerebral hemorrhage admitted to
      our hospital from January 1993 through December 1997. Aphasia was assessed using
      the aphasia scale of the Scandinavian stroke scale. Univariate and step-wise
      logistic regression analyses were performed to assess the relationships between
      the initial aphasia score, age, gender, blood volume, locations of hematoma and
      aphasia outcome. RESULTS: Step-wise logistic regression analysis revealed that
      the following two factors were independently associated with the final aphasia
      outcome: initial aphasia score (P < 0.0001) and location of hematoma involving
      the posterior limb of the internal capsule (P = 0.004). CONCLUSIONS: A
      particularly high likelihood of poor aphasia outcomes of patients with left basal
      ganglia hemorrhage are predicted in those who have poor initial aphasia score and
      whose brain computed tomography shows the hematoma involves the posterior limb of
      the internal capsule.

PMID- 11240562
TI  - Increasing prevalence of multiple sclerosis in Finland.
AB  - OBJECTIVES: To follow-up the prevalence trends of MS from 1983 to 1993 in western
      and southern Finland. MS epidemiology has been previously followed from 1964 to
      1978 in these regions. The updated prevalences were correlated with incidence
      trends in the same period. METHODS: Age-adjusted and age-specific MS prevalence
      rates were calculated for cases classified by Poser's criteria. RESULTS: In the
      western health-care districts, Seinajoki and Vaasa, prevalences in 1993 were
      202/10(5) and 111/10(5). In the southern district Uusimaa the respective figure
      was 108/10(5). In Seinajoki a significant 1.7-fold increase was found in 1993 as
      compared to 1983, mainly due to increased incidence. In Uusimaa a significant 1.2
      fold increase in prevalence was found in the presence of stable incidence. In
      Vaasa prevalence was stable, although incidence was declining. CONCLUSION: The
      prevalence of MS is increasing in Seinajoki and Uusimaa but not in Vaasa. Both
      the prevalence and incidence in Seinajoki are now among the highest reported.

PMID- 11240563
TI  - Involvement of nervous system in maternally inherited diabetes and deafness
      (MIDD) with the A3243G mutation of mitochondrial DNA.
AB  - OBJECTIVES: The A3243G mutation of mitochondrial DNA (mtDNA) has been associated
      with maternally inherited diabetes and deafness (MIDD) in a number of reports;
      however, the involvement of the nervous system has rarely been mentioned,
      prompting this exploration of the manifestation of neurological disorders in MIDD
      cases. MATERIAL AND METHODS: We investigated four generations of a large
      Taiwanese family in which MIDD is manifest. We conducted a series of clinical
      examinations, including computed tomography (CT) and magnetic resonance imaging
      (MRI) of the head, brain 99mTc-HMPAO single photon emission computed tomography
      (SPECT), cognitive function tests, and nerve conduction velocity (NCV) studies.
      Blood levels of creatine kinase (CK) and lactate, pathology of muscle biopsy
      samples and proportions of mutant mtDNA in blood cells, hair follicles, muscle
      and skin were also analyzed. Mean follow-up period was 4 years. RESULTS: The
      patients exhibited the clinical features of diabetes mellitus including
      sensorineural hearing loss, short stature, and/or histories of spontaneous
      abortion. No stroke-like episodes were reported. Analysis for mtDNA revealed that
      the A3243G mutation existed in 11 members (6 symptomatic and 5 asymptomatic
      members) of this MIDD-prone family, with the proportion of mutant mtDNA ranging
      from 21% to 47% in leukocytes. Head CT revealed diffuse brain atrophy for all 6
      (100%) patients examined and bilateral basal ganglia calcification in 4 of 6
      (67%) patients. Brain 99mTc-HMPAO SPECT revealed diminished uptake in the
      bilateral parieto-occipital or occipital regions for all 6 tested patients,
      cognitive function for these patients was normal. Results of head CT and SPECT
      were normal in one asymptomatic member of the family. One muscle biopsy revealed
      abundant ragged-red fibers with modified Gomori-trichrome stain. Muscle-enzyme
      activity and serum-lactate levels were normal. CONCLUSION: We have demonstrated
      that a wide spectrum of sub clinical pathologies of the central nervous system
      and muscle are present for this MIDD-prone family, none of whom developed typical
      MELAS during the 4-year period of follow-up study.

PMID- 11240565
TI  - S-100B and neuron-specific enolase in serum of mild traumatic brain injury
      patients. A comparison with health controls.
AB  - OBJECTIVES: The aim of the study was to determine whether serum concentrations of
      neuron-specific enolase (NSE) and S100-B in mild traumatic brain injury (MTBI)
      patients are higher than in serum of healthy controls. MATERIAL AND METHODS:
      Blood samples from 104 MTBI patients were taken shortly after the trauma for
      measurement of S-100B and NSE in serum. In 92 healthy persons these markers were
      also measured. Marker concentrations in serum of patients and controls were
      compared. In the patient group the relation between serum-marker concentrations
      and clinical symptoms and signs, that occurred shortly after the traumatic event,
      were evaluated. RESULTS: Median NSE concentration was only slightly higher in
      patients (9.8 microg/l; 10 to 90 percentile range 6.9 to 14.3 microg/ l) than in
      controls (9.4 microg/l; 6.3 to 13.3 microg/l). Median S-100B concentration was
      significantly higher in patients (0.25 microg/l; 0.00 to 0.68 microg/l) than in
      controls (0.02 microg/l; 0.00 to 0.13 microg/l). An association was found between
      S-100B concentrations and vomiting in patients. CONCLUSIONS: S-100B is a useful
      marker for brain damage in MTBI patients and seems to be associated with the
      presence of vomiting after the trauma.

PMID- 11240564
TI  - Local and systemic GM-CSF increase in Alzheimer's disease and vascular dementia.
AB  - A growing body of evidence points out the potential role of inflammatory
      mechanisms in the pathophysiology of brain damage in dementia. The aim of the
      present study was to investigate patterns of local and systemic cytokine release
      in patients with Alzheimer's disease (AD) and vascular dementia (VAD). The
      intrathecal levels of cytokines were related to neuronal damage and cerebral
      apoptosis. Twenty patients with early AD and 26 patients with VAD were analyzed
      with respect to cerebrospinal fluid (CSF) and serum levels of pro- and anti
      inflammatory cytokines. In addition, CSF levels of Fas/APO-1 and bcl-2, a measure
      for apoptosis, and Tau protein, a marker for neuronal degradation, were studied.
      Significantly increased CSF levels of GM-CSF but not of other cytokines were
      observed in both dementia groups. These patients displayed a significant
      correlation between the GM-CSF levels and the levels of Fas/APO-1 and Tau protein
      in CSF. Our study demonstrates an intrathecal production of GM-CSF, a cytokine
      stimulating microglial cell growth and exerting inflammatogenic properties. It is
      suggested that GM-CSF once secreted induces programmed cell death in the brain
      tissue of patients with dementia.

PMID- 11240566
TI  - Anti-GM1 and anti-sulfatide antibodies in polyneuropathies. Threshold titers and
      accuracy.
AB  - OBJECTIVES: To determine threshold titers and diagnostic accuracy of anti-GM1 and
      anti-sulfatide antibodies (Ab) for autoimmune polyneuropathies (PN) in overall
      and for particular subtypes of them. MATERIALS AND METHODS: In this study 84 PN
      patients, 120 epileptics and 93 healthy controls' sera were tested by enzyme
      linked immunosorbent assay for autoAbs and results confirmed by thin-layer
      chromatography. Frequencies of positive patients at increasing cut-off were
      compared to determine threshold titers. Accuracy was determined by Receiver
      Operator Characteristic analysis. RESULTS: A 1:2,000 titer for IgM anti-GM1 and a
      1:4,000 titer for IgM anti-sulfatide Ab resulted to be threshold titers for
      autoimmune PN in overall. IgM anti-GM1 and anti-sulfatide Ab had low
      discriminating capacity between autoimmune PN and other PN, but good
      discriminating capacity between motor neuropathy (for anti-GM1 Ab) or PN in IgM
      paraproteinemia or chronic painful sensory axonal PN (for anti-sulfatide Ab) and
      other PN. CONCLUSION: Our results suggest that testing IgM anti-GM1 or anti
      sulfatide Ab is useful only for diagnostic confirmation of specific subtypes of
      autoimmune PN.

PMID- 11240567
TI  - Limited somatic mosaicism for Friedreich's ataxia GAA triplet repeat expansions
      identified by small pool PCR in blood leukocytes.
AB  - OBJECTIVES: Friedreich's ataxia (FRDA), the most common inherited ataxia, is
      associated with an unstable expansion of GAA repeats in the first intron of the
      frataxin gene on chromosome 9. We investigated the mosaicism of expanded alleles
      to elucidate the basis for genotype phenotype correlations. PATIENTS AND METHODS:
      We studied the instability of the GAA repeat in blood leukocytes from 45
      individuals including 20 FRDA patients and 20 non-affected controls using small
      pool PCR combined with Southern blotting and hybridization. RESULTS: Expanded GAA
      repeats could be resolved into distinct alleles showing differences in length up
      to 1,000 triplets for an individual genome. We found a significant correlation
      between the size of the largest allele and the range of mosaicism. CONCLUSION:
      The somatic mosaicism for expanded repeats observed in FRDA patients rendered the
      precise measurement of allele sizes more difficult and may influence the results
      of studies correlating the clinical spectrum with the genotype. Following, a
      confidential prediction of the prognosis deduced from the repeat length is hardly
      possible for an individual FRDA patient.

PMID- 11240569
TI  - Reversible parkinsonism and hyperammonemia associated with portal vein
      thrombosis.
AB  - Portal-systemic encephalopathy may be seen with hyperammonemia that complicates
      chronic liver disease. We report an unusual case of reversible parkinsonism
      associated with hyperammonemia and portal vein thrombosis. An active 90-year-old
      male developed motor slowing and resting hand tremor over 6 months. Examination
      showed asterixis, bradykinesia, cogwheel rigidity, rest tremor, and a
      parkinsonian gait. Serum venous ammonia was elevated at 145 microM. The next day,
      the patient became comatose and serum ammonia was 178 microM. With lactulose
      therapy, serum ammonia level normalized and examination showed only minimal
      parkinsonism after 1 week. An abdominal CT scan identified portal vein thrombosis
      with porto-systemic shunting that reversed after 7 months of treatment.
      Examination 2 years later showed no signs of parkinsonism. Parkinsonism can
      dominate the clinical picture of patients with hyperammonemia before the onset of
      encephalopathy.

PMID- 11240568
TI  - Impact of occupational variables in carpal tunnel syndrome.
AB  - OBJECTIVE: We studied the impact of work-related factors on the outcome in
      patients operated for carpal tunnel syndrome. METHODS: The population consisted
      of 106 CTS patients who worked at the time of operation. We registered social and
      occupational data from the patients. RESULTS: Median time of sick leave was 7
      weeks for the total group. Sixty-four percent reported a relationship between
      their work and the disease. Eighty-nine percent of the operated patients returned
      to their previous work after operation. CONCLUSIONS: A majority of the patients
      attributed the CTS-related symptoms to their occupation. Work-related factors may
      therefore be one possible explanation for the socioeconomical consequences of
      CTS. A permanent drop-out from work in more than 1 out of 10 patients after CTS
      treatment indicate that CTS form a substantial socioeconomical burden in the
      society.

PMID- 11240570
TI  - How broad is the phenotype of Hallervorden-Spatz disease?
AB  - Magnetic resonance imaging (MRI) has enabled ante mortem diagnosis of
      Hallervorden Spatz disease (HSD). Childhood-onset cases are the most common type
      and usually present with progressive dystonia and dementia. The duration of
      illness is 15 to 20 years, leading to death. Presentation in adulthood and
      infancy have also been reported, however again the progression is usually
      inexorable. We present a 30-year-old woman who developed cognitive and motor
      developmental delay from the age of 8 months. There was further cognitive decline
      in her late teenage years with seizures and then more recent motor decline with
      dystonia. The imaging appearance was of iron deposition in the globus pallidus
      and substantia nigra leading to a diagnosis of HSD. The increased availability of
      MRI has allowed more cases of HSD to be diagnosed in life but as our case
      illustrates classification of the disease may need to be further examined.

PMID- 11240571
TI  - Interleukin-1beta and the etiology of depression.

PMID- 11240572
TI  - A review of psychosocial outcome in patients with bipolar disorder.
AB  - OBJECTIVE: The aim of this paper is to review outcome in patients with bipolar
      disorder as assessed by interepisode level of functioning, as until recently this
      dimension of outcome has been relatively under-emphasized. METHOD: Studies that
      examined psychosocial outcome in bipolar disorder were reviewed on the basis of
      rating measurements employed, length of follow-up, number of subjects followed
      and degree of impairment reported. Studies were included only if results from
      patients with bipolar and unipolar disorder were reported in such a way that the
      groups could be distinguished. RESULTS: When studies of psychosocial outcome in
      bipolar disorder are examined in aggregate, it appears that 30-60% of individuals
      with this disorder fail to regain full functioning in occupational and social
      domains. CONCLUSION: This review highlights the fact that inter-episode
      functional recovery is incomplete in some patients, suggesting that comprehensive
      rehabilitative assessment and intervention may be essential to reduce the
      morbidity associated with this disorder.

PMID- 11240573
TI  - Visual binding abilities in the initial and advanced stages of schizophrenia.
AB  - OBJECTIVE: The study tests the hypothesis that intramodal visual binding is
      disturbed in schizophrenia and should be detectable in all illness stages as a
      stable trait marker. METHOD: Three groups of patients (rehospitalized chronic
      schizophrenic, first admitted schizophrenic and schizotypal patients believed to
      be suffering from a pre-schizophrenic prodrome) and a group of normal control
      subjects were tested on three tasks targeting visual 'binding' abilities (Muller
      Lyer's illusion and two figure detection tasks) in addition to control parameters
      such as reaction time, visual selective attention, Raven's test and two
      conventional cortical tasks of spatial working memory (SWM) and a global local
      test. RESULTS: Chronic patients had a decreased performance on the binding tests.
      Unexpectedly, the prodromal group exhibited an enhanced Gestalt extraction on
      these tests compared both to schizophrenic patients and to healthy subjects.
      Furthermore, chronic schizophrenia was associated with a poor performance on
      cortical tests of SWM, global local and on Raven. This association appears to be
      mediated by or linked to the chronicity of the illness. CONCLUSION: The study
      confirms a variety of neurocognitive deficits in schizophrenia which, however, in
      this sample seem to be linked to chronicity of illness. However, certain aspects
      of visual processing concerned with Gestalt extraction deserve attention as
      potential vulnerability- or prodrome- indicators. The initial hypothesis of the
      study is rejected.

PMID- 11240574
TI  - Working memory in schizophrenia and mania: correlation with symptoms during the
      acute and subacute phases.
AB  - OBJECTIVE: The aims of this study were to examine working memory in the acute
      subacute phase of schizophrenia and mania and to examine correlations between
      working memory and specific symptom domains. METHOD: Visuospatial working memory
      and symptom profiles were assessed in three groups (schizophrenia group, n= 19;
      mania, n= 12; controls, n= 19) on two occasions separated by 4 weeks. RESULTS:
      Both patient groups had significant deficits on working memory compared to the
      well controls and the schizophrenia and mania groups were equally impaired. All
      groups showed equivalent improvement over time. In the patient groups, impaired
      working memory was significantly correlated with the presence of both negative
      symptoms and positive thought disorder. CONCLUSION: Impaired working memory is
      found in both schizophrenia and mania during the acute subacute phases. Further
      research is required in order to clarify the neurocognitive mechanisms linking
      impaired working memory with both negative symptoms and positive thought
      disorder.

PMID- 11240575
TI  - Gender-related differences in the onset of panic disorder.
AB  - OBJECTIVE: To investigate gender-related differences in premorbid conditions and
      in the role of triggering events in the onset of panic disorder (PD). METHOD: One
      hundred and eighty-four out-patients with a principal diagnosis of PD (DSM-IV)
      were evaluated with a semi-structured interview to generate Axis I and Axis II
      diagnoses according to DSM-IV, to collect family history of psychiatric disorders
      and life events. The statistical analysis was performed comparing men and women.
      RESULTS: Men and women showed similar age at onset of PD. A family history of
      mood disorders characterized females. Men had higher rates of cyclothymia, body
      dysmorphic disorder and depersonalization disorder preceding PD, while women had
      higher rates of bulimia nervosa. Dependent and histrionic PDs were more common
      among women, while borderline and schizoid PDs were more common among men. Life
      events showed a significant role in precipitating PD onset in women. CONCLUSION:
      Premorbid clinical conditions of PD seem to differentiate between males and
      females in the role of precipitating events.

PMID- 11240576
TI  - Operating conditions of psychiatric hospitals and early readmission--effects of
      high patient turnover.
AB  - OBJECTIVE: To study the association between hospitals' operating conditions and
      the risk of early readmission. The hypothesis was that high patient turnover
      might lead to a rise in the risk of readmission soon after discharge (within 30
      days). METHOD: A multivariate model including hospital and patient variables was
      tested using Cox's regression analysis, adjusting for clustering effects. The
      material included data from 20 hospitals, with 5,520 patients in the final model.
      RESULTS: High patient turnover (annual discharges per bed) was significantly
      associated with an increased risk of readmission (hazard ratio (HR)= 3.37 (95% CI
      = 2.39-4.75)). In addition, being discharged from a ward with relatively low
      access to therapists increased the hazard further. CONCLUSION: High patient
      turnover at the discharging ward was found to increase the patients' hazard of
      early readmission. This observation supports the hypothesis of a link between the
      operation conditions of the hospitals and patient outcome on a short time-scale.

PMID- 11240577
TI  - A statistical model for length of psychiatric in-patient treatment and an
      analysis of contributing factors.
AB  - OBJECTIVE: Direct illness costs in psychiatry are strongly related to the length
      of in-patient stay (LOS). Prior studies have shown that LOS depends upon many
      factors; however, there is no systematic work on their interrelation and relative
      contribution. METHOD: A detailed statistical analysis of the factors explaining
      LOS for n = 4,706 consecutive admissions (1994-97) to the psychiatric hospital of
      the University of Tubingen is presented. RESULTS: The distribution of LOS follows
      an exponential decay function, suggesting a hazard-based process. Cox regression
      indicates that the incidence of discharge and hence LOS is modulated by a number
      of illness-related and other factors, and their relationship is explored.
      CONCLUSION: While a linear model is commonly assumed, LOS in psychiatry is
      governed by a hazard-based process. As a tool in quality management, LOS data for
      psychiatric hospitals might be routinely analyzed and the effects of non-illness
      related factors minimized.

PMID- 11240578
TI  - Ward atmosphere in acute psychiatric in-patient care: patients' perceptions,
      ideals and satisfaction.
AB  - OBJECTIVE: To investigate the relationship between patients' perception of the
      real and ideal ward atmosphere and their satisfaction. METHOD: Patients filled in
      the Ward Atmosphere Scale (WAS, Real and Ideal Form) and a satisfaction
      questionnaire. Patient characteristics were derived from clinical assessments.
      RESULTS: WAS ratings were almost independent of patient characteristics. Patients
      in locked wards perceived more anger and aggression and patients subjected to
      coercive measures perceived less autonomy and practical orientation. Patient
      satisfaction was predicted by higher scores on the WAS Relationship- and System
      Maintenance dimensions, explaining 41% of the variance. In particular support,
      order and organization predicted satisfaction. Except from the areas of
      anger/aggression and staff control, patients gave the 'ideal' ward higher ratings
      on all subscales. The perceived gap between the 'ideal' and 'real' ward explained
      45% of variance in satisfaction. CONCLUSION: Patients' perception of ward
      atmosphere is a clinically meaningful measure appearing to be a strong predictor
      of satisfaction.

PMID- 11240579
TI  - What to do about mental disorder--help-seeking recommendations of the lay public.
AB  - OBJECTIVE: Sociocultural factors have been recognized as an important predictor
      in shaping help-seeking behaviour. METHOD: We investigated attitudes of the lay
      public toward help-seeking for mental disorders in a population survey (n =
      1,564) conducted in the new Laender of Germany. After presenting a vignette
      depicting a person either with major depression or with schizophrenia (DSM-III
      R), we inquired about help-seeking recommendations. employing a qualitative
      approach. RESULTS: The lay support system plays an significant role in initially
      dealing with mental disorders. However, help-seeking recommendation differed for
      depression and schizophrenia. In depression, support from the lay system was more
      often considered. In schizophrenia, public opinion favoured the expert system. If
      primary suggestions fail the expert system is clearly favoured regardless of the
      disorder in question. CONCLUSION: Lay public's opinion has to be taken into
      account of in mental health care planning to make services more acceptable to the
      consumer and their social network.

PMID- 11240580
TI  - Raised levels of plasma interleukin-1beta in major and postviral depression.
AB  - OBJECTIVE: Interleukin-1beta (IL-1beta) is released as part of the acute phase
      immune response and can directly stimulate the release of corticotrophin
      releasing hormone and thus induce hypothalamic pituitary adrenal axis
      hyperactivity. Major depression has been shown to be accompanied by both an acute
      phase immune response, including raised IL-1beta production and hypothalamic
      pituitary adrenal axis hyperactivity. In this study the possible role of IL-1beta
      in major depression and postviral depression was investigated. METHOD: Plasma IL
      1beta levels were measured in four groups; patients suffering from postviral
      depression (n= 17), patients with major depression (n = 20), subjects who were
      postviral and euthymic (n= 12) and normal controls (n = 20). RESULTS: IL-1beta
      serum concentrations were significantly elevated in both groups of depressed
      patients compared to controls. The serum concentrations of IL-1beta were higher
      in the postviral group than in the major depression group; this difference was
      not significant. CONCLUSION: These data confirm previous suggestions of elevated
      IL-1beta levels in major depression and postviral depression. IL-1beta is known
      to induce depressive symptoms as well as sickness behaviour and may contribute to
      the hypothalamic pituitary adrenal axis hyperactivity found in mood disorders.

PMID- 11240581
TI  - Platelet serotonin transporters and the  transporter gene in control subjects,
      unipolar patients and bipolar patients.
AB  - OBJECTIVE: The purpose of the present study was to relate the number of platelet
      serotonin transporters in unipolar and bipolar patients and in control subjects
      to two polymorphisms in the serotonin transporter gene: a VNTR in intron 2 and a
      deletion/insertion in the promoter region. METHOD: Density of platelet serotonin
      transporters was determined by radioligand binding analysis. Genotyping was
      performed by PCR amplification of polymorphic regions followed by size
      determination of the obtained fragments. RESULTS: The control subjects and the
      two groups of patients were similar with respect to the genotype and allele
      distribution belonging to the two polymorphisms in the serotonin transporter gene
      for. An interaction between status (control, unipolar- or bipolar patient) and
      VNTR genotype regarding the number of platelet serotonin transporters was
      observed; unipolar patients with the genotype 12/10 had more platelet serotonin
      transporters than bipolar patients and controls with this genotype. No
      association related to the polymorphism was found in the promoter region of the
      serotonin transporter gene. CONCLUSION: An association was observed between the
      polymorphism in intron 2 of the serotonin transporter gene and the number of
      platelet serotonin transporters. Unipolar patients with a particular genotype had
      more platelet serotonin transporters than the corresponding controls and bipolar
      patients.

PMID- 11240583
TI  - Biography.

PMID- 11240582
TI  - Naltrexone as a treatment of self-injurious behavior--a case report.
AB  - OBJECTIVE: Self-injurious (SIB) is a phenomenon associated with different
      psychopathological conditions such as psychosis, mental retardation and
      especially severe personality disorders--mainly of the borderline subtype. It has
      been suggested that a blockade of the endogenous opoid system might lead to a
      reduction of the urge to SIB. METHOD: The case and successful treatment of SIB
      with naltrexone in a patient with borderline personality disorder and dysthymia
      is described. RESULTS: After treatment trials with neuroleptics, antidepressants
      and valproate the patient was treated with naltrexone in a dosis of 50 mg/day and
      did not show SIB over a follow-up period of 32 weeks. CONCLUSION: Naltrexone
      could be effective in reducing SIB in patients with psychiatric disorders by
      blocking the positive reinforcement of SIB, which is released by the release of
      endogenous opoides. Placebo-controlled studies of the efficacy of naltrexone in
      treating SIB should be undertaken.

PMID- 11240584
TI  - Antidepressants and suicide prevention in Hungary.

PMID- 11240585
TI  - A possible role for gap junctions in generation of very fast EEG oscillations
      preceding the onset of, and perhaps initiating, seizures.
AB  - PURPOSE: We propose an experimentally and clinically testable hypothesis,
      concerning the origin of very fast (> approximately 70 Hz) EEG oscillations that
      sometimes precede the onset of focal seizures. These oscillations are important,
      as they may play a causal role in the initiation of seizures. METHODS: Subdural
      EEG recordings were obtained from children with focal cortical dysplasias and
      intractable seizures. Intra- and extracellular recordings were performed in rat
      hippocampal slices, with induction of population activity, as follows: (a) bath
      applied tetramethylamine (an intracellular alkalinizing agent, that opens gap
      junctions); (b) bath-applied carbachol, a cholinergic agonist; and (c) focal
      pressure ejection of hypertonic K+ solution. Detailed network simulations were
      performed, the better to understand the cellular mechanisms underlying
      oscillations. A major feature of the simulations was inclusion of axon-axon gap
      junctions between principal neurons, as supported by recent experimental data.
      RESULTS: Very fast oscillations were found in children before seizure onset, but
      also superimposed on bursts during the seizure, and on interictal bursts. In
      slice experiments, very fast oscillations had previously been seen on interictal
      like bursts; we now show such oscillations before, between, and after
      epileptiform bursts. Very fast oscillations were also seen superimposed on gamma
      (30-70 Hz) oscillations induced by carbachol or hypertonic K+, and in the latter
      case, very fast oscillations became continuous when chemical synapses were
      blocked. Simulations replicate these data, when axonal gap junctions are
      included. CONCLUSIONS: Electrical coupling between principal neurons, perhaps via
      axonal gap junctions, could underlie very fast population oscillations, in
      seizure-prone brain, but possibly also in normal brain. The anticonvulsant
      potential of gap-junction blockers such as carbenoxolone, now in clinical use for
      treatment of ulcer disease, should be considered.

PMID- 11240586
TI  - An animal model of nonconvulsive status epilepticus: a contribution to clinical
      controversies.
AB  - PURPOSE: To characterize electroencephalographic and behavioral effects as well
      as electrophysiologic and morphologic consequences of a subconvulsive dose of
      pilocarpine in lithium chloride-pretreated rats. METHODS: Pilocarpine (15 mg/kg)
      was administered intraperitoneally to adult rats pretreated with lithium chloride
      (3 mEq/kg, i.p.). Behavior was observed for 2 h and videotaped in three
      consecutive sessions. At the same time, EEG was recorded from the sensorimotor
      cortex and the dorsal hippocampus. Threshold intensities of currents necessary to
      elicit hippocampal afterdischarges were determined 24 h and 1 week after the
      pilocarpine administration. The brains were histologically examined 1 week after
      pilocarpine administration using Nissl stain. RESULTS: Pilocarpine induced time
      limited nonconvulsive status epilepticus (NCSE). Epileptic EEG activity
      concurrent with prominent behavioral features was observed both in the neocortex
      and, predominantly, in the hippocampus. No changes in afterdischarge thresholds
      were observed in the dorsal hippocampus 24 h and 1 week after NCSE. One week
      after NCSE, seizure-related brain damage was found mainly in the motor
      neocortical fields. CONCLUSIONS: Pilocarpine-induced NCSE in rats strongly
      resembles a short-term human complex partial status epilepticus. Our animal model
      is suitable for studying the possible adverse effects of prolonged nonconvulsive
      seizures.

PMID- 11240588
TI  - Time course of postoperative recovery of N-acetyl-aspartate in temporal lobe
      epilepsy.
AB  - PURPOSE: To assess the time course of increases in N-acetyl-aspartate/creatine
      (NAA/Cr), which can be measured using proton MR spectroscopic imaging (1H-MRSI),
      in patients with intractable nonlesional temporal lobe epilepsy (TLE) after
      successful epilepsy surgery. METHODS: We performed pre- and postoperative 1H-MRSI
      in 16 seizure-free (SF) patients and 16 not seizure-free (NSF) TLE patients. We
      calculated a mixed-design analysis of variance (ANOVA) between SF and NSF groups,
      ipsi- and contralateral to the side of operation, and pre- and postoperative
      NAA/Cr measurements. We applied nonlinear regression between pre- and
      postoperative NAA/Cr differences and the time interval between 1H-MRSI scans to
      fit a negative exponential model to NAA recovery. RESULTS: Mixed-design ANOVA
      revealed that (a) postoperative NAA/Cr was significantly higher in SF than in NSF
      patients (p = 0.02) and that (b) in the SF group, postoperative NAA/Cr values
      were significantly higher than preoperative values (p < 0.05) and returned to the
      normal range in most patients. According to our nonlinear regression model, in SF
      patients, there was a 50% increase relative to preoperative NAA/Cr values after
      5.8 months, whereas an improvement of 95% was reached after 25 months.
      CONCLUSIONS: Our results extend preliminary observations of postoperative NAA
      recovery of SF patients by characterizing the time course of recovery as an
      exponential function with a half-time of approximately 6 months. The reversal of
      neuronal metabolic dysfunction remote from the epileptic focus may underlie the
      clinical observation of improvement of cognitive dysfunction after successful
      epilepsy surgery.

PMID- 11240587
TI  - Altered activities of rat brain metabolic enzymes in electroconvulsive shock
      induced seizures.
AB  - PURPOSE: Electroconvulsive shock (ECS) induces generalized seizure activity and
      provides an excellent experimental model for studying the effects of global
      electrical stimulation on various biochemical parameters. The aim of this work
      was to investigate the influence of a single or repeated ECS-induced seizures on
      rat brain metabolism. METHODS: Experiments were carried out on female Hannover
      Wistar rats divided into four groups: (a) the control group, which was intact;
      (b) the 1ECS group, which was killed 2 h after single ECS; (c) the 5ECS group
      with 24 h rest, which was killed 24 h after the fifth daily ECS; and (d) the
      10ECS group with 48 h rest, which was given ECS every 48 h and killed 24 h after
      the tenth ECS. Activities of glutamate dehydrogenase (GLDH), aspartate
      aminotransferase (AST), alanine-aminotransferase (ALT), gamma-glutamyltransferase
      (GGT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and creatine
      kinase (CK) in the frontal cortex, cerebellum, hippocampus, and pons/medulla
      regions were determined. RESULTS: Increased AST, ALP, LDH, and CK activities were
      detected in all examined regions of the 1ECS and 5ECS groups. ALT activity was
      increased in both these groups, except in the hippocampus of the 5ECS group,
      where increased GGT activity was detected. In the hippocampus of 1ECS group, GLDH
      activity was decreased. Increased hippocampal AST and cortical CK activities,
      together with increased LDH activities in the cortex, cerebellum, and
      pons/medulla, were found. CONCLUSIONS: ECS treatment induces region-specific
      changes in metabolic activity. Neither a 24-h nor a 48-h rest period between two
      ECSs was sufficient for complete brain recovery, although most of the observed
      increased enzyme activities present in 1ECS and 5ECS were not present in 10ECS.

PMID- 11240589
TI  - Focal functional deficits in temporal lobe epilepsy on PET scans and the
      intracarotid amobarbital procedure: comparison of patients with unitemporal
      epilepsy with those requiring intracranial recordings.
AB  - PURPOSE: To analyze the relationship between the intracarotid amobarbital
      procedure (IAP) and positron emission tomography (PET) and study the lateralizing
      value of these tests in patients with unitemporal epilepsy and those requiring
      intracranial recordings. METHODS: We compared 51 patients with unitemporal
      epilepsy (group1) with 26 patients in whom surface recordings failed to reveal a
      distinct unitemporal focus, necessitating invasive recordings (group 2). RESULTS:
      The brain magnetic resonance imaging (MRI) scans for group 1 showed mesial
      temporal sclerosis in 70.5% of the patients. PET showed unilateral temporal
      hypometabolism in 88%. In addition, 74.5% of the patients in group 1 had impaired
      memory on the epileptogenic side on the IAP, and 89.4% of those patients also had
      ipsilateral temporal hypometabolism on PET scans. All the group 1 patients
      underwent temporal resections. The pathologic examination showed hippocampal
      sclerosis in 72% of the patients. Eighty percent of group 1 patients became
      seizure free, and 16% had rare seizures (follow-up, 2-7 years). MRIs for group 2
      showed mesial temporal sclerosis in 31% of the patients; PET scans showed
      temporal hypometabolism in 39%. The IAP was lateralized in 47.8%. Sixty-nine
      percent had temporal lobe resections. The pathologic examination showed
      hippocampal sclerosis in 44% of the patients. Forty-four percent of group 2
      patients became seizure free, and 27.7% had rare seizures (follow-up, 2-8 years).
      CONCLUSIONS: Ninety-six percent of the patients with unitemporal foci had focal
      functional deficits on the epileptogenic side on 18-fluorodeoxyglucose-(FDG) PET
      scans, the IAP, or both. The results of the FDG-PET were predictive of impaired
      memory on the IAP. Memory impairment contralateral to the temporal hypometabolism
      found on the PET scans was never seen. These patients had an excellent outcome.
      In contrast, <50% of the patients requiring intracranial recordings had focal
      functional deficits, suggesting that more a diffuse pathology may account for
      their less favorable outcome.

PMID- 11240590
TI  - Genetic predisposition to severe myoclonic epilepsy in infancy.
AB  - PURPOSE: To address genetic predisposition to febrile convulsions (FCs) and
      epilepsy as an etiologic background of severe myoclonic epilepsy in infancy
      (SMEI). METHODS: Familial antecedents of epilepsy and FCs were analyzed in four
      groups of patients with SMEI (65 cases), FCs (57 cases), childhood absences (67
      cases), and a control group of patients with no neurologic problems (64 cases).
      RESULTS: Patients with SMEI and those with FCs had significantly increased
      incidence of FCs in their relatives compared with those with absence epilepsy and
      with the control group. The incidence of epilepsy in relatives of patients with
      SMEI and absence epilepsy was increased compared with that in the control group
      and reached statistical significance. Epilepsy in relatives with SMEI had the
      characteristics of idiopathic generalized epilepsy. CONCLUSIONS: A genetic
      predisposition could determine three types of epileptic syndromes: FCs,
      idiopathic generalized epilepsy, and SMEI.

PMID- 11240591
TI  - Contribution of the MHC class II antigens to the etiology of infantile spasm in
      Mexican Mestizos.
AB  - PURPOSE: Infantile spasms (ISs) are age-dependant epileptic seizures, which may
      be flexor, extensor, lightning or nods, or mixed. The aim of this study was the
      analysis of genetic factors within the human leukocyte antigen (HLA) complex
      associated with ISs. METHODS: Sixty-five patients diagnosed according to the
      established international criteria were compared with 229 healthy individuals;
      all of them were Mexican Mestizos. Five families were also analyzed (seven
      affected and five healthy sibs); HLA class I and class II antigens were typed
      using the standard microlymphocytotoxicity methods. RESULTS: The findings showed
      female gender preference (2:1). Two thirds were symptomatic, and prevalent
      seizures were of mixed type (67%). A strong association with HLA-DR17 was
      detected in the IS group (pc < 0.01; OR = 3.6; EF = 0.20). DR17 was also found
      increased in the symptomatic patients (p = 0.009; OR = 3.16) and in those with
      other types of seizures (p = 0.001; OR = 2.0). Conversely, HLA-DQ6 was
      significantly decreased (pc < 0.002; PF = 0.37) in the total and in the
      symptomatic groups (p < 0.01). Haplotype linkage was not confirmed in the
      families; however, those with more than one affected sib shared at least one
      haplotype. CONCLUSIONS: These findings suggest the contribution of DR locus to
      the susceptibility and the participation of DQ region in the resistance to IS.
      Severity seems also to be influenced by HLA-DR17, and therefore class II typing
      may be a helpful tool for disease prognosis.

PMID- 11240592
TI  - Circulating levels of allopregnanolone, an anticonvulsant metabolite of
      progesterone, in women with partial epilepsy in the postcritical phase.
AB  - PURPOSE: Several lines of evidence indicate that there exists a relation between
      ovarian hormones and epilepsy. Estrogens decrease seizure threshold and increase
      brain excitability, whereas progesterone has an inhibitory effect and reduces
      epileptiform activity. Recently considerable interest has turned to neuroactive
      steroids, a group of progesterone metabolites, as endogenous modulators of
      excitability of the central nervous system (CNS). Their ability to alter neuronal
      firing rapidly occurs through interaction with gamma-aminobutyric acid (GABA) A
      receptor complex. In a previous experience, serum allopregnanolone (3alpha-OH
      5alpha-pregnan-20-one) levels were measured in 15 women with partial epilepsy in
      the intercritical phase, and no significant differences were found between
      patients and control subjects. METHODS: To find out if there are changes in serum
      allopregnanolone levels after epileptic seizure, blood samples were drawn
      immediately, 15 min, and 6 h after a seizure in seven fertile females with
      partial epilepsy. RESULTS: The most interesting finding is that allopregnanolone
      increases in serum during the first 15 min after partial seizures (p < 0.05) and
      decreases after 6 h. CONCLUSIONS: These data are consistent with a role for
      allopregnanolone in the control of neuronal excitability and seizures.

PMID- 11240594
TI  - Multiple subpial transections: the Yale experience.
AB  - PURPOSE: Although resection of an epileptogenic region is the mainstay of
      epilepsy surgery, epileptogenic areas in functionally critical cortex cannot be
      approached in that manner. Multiple subpial transection (MST) was developed to
      treat those refractory seizures without causing unacceptable neurologic deficit.
      We review our experience with this technique. METHODS: Twelve patients who
      underwent MST with or without resection between 1990 and 1998 were
      retrospectively reviewed with regard to seizure and neurologic outcome, and
      predictive factors. RESULTS: Five (42%) of 12 patients obtained a significant
      improvement in seizure frequency, and two other patients had a marked decrease in
      the severity of their seizures. Resection with MST reduced seizure frequency
      more, but this was not a significant difference. No predictive factors for
      outcome were identified. Only one patient sustained any persistent neurologic
      deficit. CONCLUSIONS: In selected patients, MST may be a viable alternative when
      the epileptogenic focus lies in unresectable cortex. A multicenter study with
      appreciable patient numbers will be necessary to define predictive factors for
      success.

PMID- 11240593
TI  - Alfentanil-induced epileptiform activity: a simultaneous surface and depth
      electroencephalographic study in complex partial epilepsy.
AB  - PURPOSE: Alfentanil is a high potency mu opiate receptor agonist commonly used
      during presurgical induction of anesthesia. This and other opiate receptor
      agonists have demonstrated proconvulsant effects in animals, but these properties
      have been less consistently demonstrated in humans. Most human scalp EEG studies
      have failed to demonstrate induction of epileptiform activity with these agents,
      which is inconsistent with findings using intracranial EEG. Simultaneous scalp
      and depth EEG recordings have yet to be performed in this setting. The
      relationship between opiate dose and proconvulsant activity is unclear. METHODS:
      Simultaneous scalp and depth electrode recordings were performed on five patients
      with complex partial epilepsy (CPE) who underwent alfentanil anesthesia induction
      before depth electrode removal. Consecutive equal bolus doses of alfentanil were
      administered to each patient according to strict time intervals so as to assess
      their correlation with any induced epileptiform activity. RESULTS: Epileptiform
      activity was induced by alfentanil in three of five patients. Two of these
      patients had electrographic seizures. Epileptiform activity was only detected
      from the depth electrodes, occurring within 2 min of the first bolus dose in all
      three cases. Further increase or spread of epileptiform activity did not occur
      despite cumulative bolus doses of alfentanil. CONCLUSIONS: Alfentanil is
      proconvulsant in patients with CPE. Induced seizures may be subclinical and lack
      a scalp EEG correlate. There is a complex dose-response relationship. Alfentanil
      induction of anesthesia should be approached with caution in patients with CPE.

PMID- 11240595
TI  - The effect of lamotrigine on epileptiform discharges in young patients with drug
      resistant epilepsy.
AB  - PURPOSE: In a double-blind crossover study with lamotrigine (LTG), we
      investigated a possible relationship between the clinical responses and changes
      of the amount of epileptiform activity in EEG. METHODS: Twelve patients, aged 4
      21 years, with generalized drug-resistant epilepsy who had responded to LTG,
      completed the study. Twenty-four-hour video-EEGs were taken during control,
      placebo, and drug phases. The amounts of epileptiform discharges were estimated
      and compared with the clinical effects. RESULTS: The duration of periods of
      repeated epileptiform discharges was significantly reduced during the LTG phase
      compared with the placebo phase (n = 12, p = 0.04). Ten patients showed a
      reduction of the amount of epileptiform discharges in the LTG phase by a mean of
      81% (range, 17-100%). Periods of repeated epileptiform discharges with duration
      longer than 30 s were significantly reduced in length (p = 0.03) and number (p =
      0.04) during the LTG phase compared with the placebo phase. Shorter periods of
      epileptiform discharges and the numbers of single epileptiform discharges were
      not affected. In five patients there was a seizure reduction (>/=50%) concomitant
      with the reduction of epileptiform discharges in the EEG. The behavior improved
      during LTG treatment in all patients. The patients became more alert, and their
      concentration and performance improved, according to their parents and the
      medical personnel. CONCLUSIONS: LTG in dosages of 1-8 mg/kg body weight was found
      to depress relatively long episodes of interictal, repetitive, epileptiform
      activity in young patients with drug-resistant epilepsy, whereas short episodes
      were not affected. It depressed seizures in about half of the patients studied
      but gave improvements of behavior in all patients.

PMID- 11240596
TI  - Adverse event monitoring in lamotrigine patients: a pharmacoepidemiologic study
      in the United Kingdom.
AB  - PURPOSE: This postmarketing surveillance study of lamotrigine (LTG) was performed
      to provide complementary data to large-scale Prescription-Event Monitoring study
      with a retrospective case records survey in five tertiary referral epilepsy
      centres in the United Kingdom. METHODS: Adverse events were recorded and compared
      with those of two other new antiepileptic drugs (AEDs), gabapentin (GBP) and
      vigabatrin (VGB). All deaths were followed up and standardised mortality ratios
      (SMRs) were calculated. Serious adverse events were assessed individually.
      RESULTS: A total of 2,701 patients was identified as being exposed to LTG and/or
      the comparators. It was necessary to exclude 1,326 patients because LTG and/or
      comparators had been commenced outside the study centres. The adverse events with
      LTG reported by this study were similar to those reported in the literature. Skin
      rash was the major adverse event. Life-threatening hepatic failure, acute
      exacerbation of ulcerative colitis, disseminated intravascular coagulation, and
      renal failure were reported. No death could be directly attributed to the use of
      LTG. The SMR was slightly higher than that reported in the literature; this
      probably reflects severity of epilepsy in the study population. CONCLUSIONS: The
      safety profile of LTG was similar to that in the large-scale Prescription-Event
      Monitoring study and generally acceptable. Life-threatening adverse reactions
      were rare.

PMID- 11240597
TI  - Fosphenytoin: pharmacokinetics and tolerance of intramuscular loading doses.
AB  - PURPOSE: Fosphenytoin (FPHT; Cerebyx) is well absorbed when given intramuscularly
      (IM). All prior pharmacokinetic studies had the first plasma sample obtained 30
      min after IM administration. The objectives of this study were to determine the
      rate and extent of FPHT absorption and to evaluate the tolerability of IM FPHT
      compared with IM saline. METHODS: This was an open-label, double-blinded study in
      which patients received 10 mg/kg dose of IM FPHT in one gluteus and IM saline in
      the other gluteus. Half the patients received saline injection of equal volume to
      FPHT (up to 19.5 mL); the other half received 2 mL of saline. Neurologic
      examination, vital signs, PHT blood samples, injection site examination, and
      subjective pain scores at injection site were obtained before and at timed
      intervals for 6 h. RESULTS: Total PHT serum concentrations 10 microg/mL were
      obtained in 5 min in 14.3% of patients and in 26.3% after 10 min. More than half
      the patients had therapeutic serum concentrations at 30 min; 45.8% of patients
      reported no pain at either the FPHT or saline injection site. No significant
      difference in pain was noted between FPHT and saline injection sites at 60 min
      and thereafter. Early decrease in blood pressure occurred but was not clinically
      significant. Classic PHT-induced central nervous system (CNS) side effects were
      evident in one third of patients within 1 h after injection. CONCLUSIONS: (a) IM
      FPHT is rapidly absorbed (therapeutic levels achieved as early as 5-20 min). (b)
      IM FPHT is well tolerated by most patients irrespective of injection volume.

PMID- 11240598
TI  - Antiepileptic drug withdrawal in patients with temporal lobe epilepsy undergoing
      presurgical video-EEG monitoring.
AB  - PURPOSE: To investigate antiepileptic drug (AED) withdrawal during video-EEG
      monitoring in adult patients with temporal lobe epilepsy (TLE). METHODS: Between
      1995 and 1997, 102 consecutive patients with refractory TLE were admitted to the
      epilepsy monitoring unit for presurgical evaluation. Patients were monitored with
      ongoing AEDs being rapidly decreased and discontinued in 4-6 days. The monitoring
      was continued until sufficient numbers of seizures were recorded. Serum AED
      levels were checked at admission and after the first complex partial seizure
      (CPS). RESULTS: In all, 89 patients had 429 CPSs (mean, 4.8 per patient),
      including 156 (36.4%) secondarily generalized. A mean of 153.8 h (16-451 h) was
      required for completing the monitoring in each patient. Forty-three (48.3%)
      patients experienced seizure clusters, and eight (9.0%) had generalized seizures
      that had never occurred or had been absent for years. However, none evolved to
      status epilepticus. Carbamazepine was the most commonly used AED in 71.9% of
      patients, followed by valproate and phenytoin. When the first CPS occurred, mean
      77.2 h since the beginning of the monitoring, serum levels of these three AEDs
      were mostly subtherapeutic rather than minimal. CONCLUSIONS: Acute AED withdrawal
      effectively provoked seizures in TLE patients undergoing presurgical video-EEG
      monitoring. However, nearly 50% of patients had seizure clusters or secondarily
      generalized seizures. Serum AED levels were mostly subtherapeutic when the first
      CPS occurred.

PMID- 11240600
TI  - Visual field loss associated with vigabatrin: quantification and relation to
      dosage.
AB  - PURPOSE: To describe the correlation between visual field loss and the duration,
      dosage, and total amount of vigabatrin (VGB) medication in a group of patients
      with epilepsy. Co-medication of antiepileptic drugs (AEDs) and compliance were
      also studied. METHODS: Ninety-two patients (53 male and 39 female) taking VGB
      medication in the past or the present, attending the Outpatient Epilepsy Clinic
      in Utrecht, were examined with the Goldmann perimeter. The amount of visual field
      loss was calculated by the Esterman grid method and by a new method, with which
      the percentage surface loss of the visual field is measured. A complete drug
      history was compiled, specifying the amount and duration of VGB medication.
      Concomitant AED medication was noted. Serum levels of AEDs were determined.
      RESULTS: Linear regression showed the total amount of VGB as the most significant
      parameter to predict visual field loss (p < 0.001). Further, men were more
      affected than women (p = 0.026). Compliance was good, and other AEDs did not
      influence the results. CONCLUSIONS: Because prolonged use of VGB medication is
      correlated with the amount of visual field loss, VGB should be prescribed only
      when there are no alternatives. In such cases, we recommend an examination of the
      peripheral visual field before starting therapy and a repeated examination every
      6 months.

PMID- 11240599
TI  - Distribution of valproate to subdural cerebrospinal fluid, subcutaneous
      extracellular fluid, and plasma in humans: a microdialysis study.
AB  - We sought to study the time course of the distribution of valproate (VPA) to
      subdural cerebrospinal fluid (CSF) in relation to subcutaneous extracellular
      fluid (ECF) and plasma after a single oral dose and to study the distribution to
      these three compartments under steady-state conditions. Microdialysis was used to
      estimate unbound VPA concentrations in subdural CSF and subcutaneous ECF, and
      blood samples were drawn for estimation of total and unbound VPA plasma
      concentrations in four patients with drug-resistant partial epilepsy undergoing
      presurgical evaluation with subdural EEG monitoring. Three patients were given a
      single oral dose of VPA, and one patient was receiving regular VPA treatment. VPA
      was analyzed by gas chromatography with flame ionization detection. The
      distribution of VPA to subdural CSF was rapid (Tmax, 3.5 h in two patients and
      5.5 h in one patient) and subject to a minor delay in all three patients compared
      with that in the subcutaneous tissue ECF (Tmax, 2.5 h in all three patients),
      which in turn exhibited no evidence of a distribution delay compared with plasma.
      Subdural CSF levels of VPA were slightly lower than subcutaneous ECF levels (mean
      ratio, 0.78) and unbound plasma levels (mean ratio, 0.91). VPA rapidly enters the
      subdural CSF in unbound concentrations marginally lower than those obtained in
      subcutaneous ECF and plasma. These findings provide a pharmacokinetic rationale
      for acute administration of VPA. The good correlation between VPA concentrations
      in subcutaneous ECF and subdural CSF indicates that estimation of unbound VPA
      concentrations in subcutaneous tissue using microdialysis sampling has the
      potential to be useful for monitoring purposes.

PMID- 11240601
TI  - Mental retardation in pediatric candidates for epilepsy surgery: the role of
      early seizure onset.
AB  - PURPOSE: We sought to determine whether early age at seizure onset is a risk
      factor for mental retardation, independent of etiology. Assessment of risk for
      mental retardation with continued uncontrolled seizures plays a role in
      considerations of timing for epilepsy surgery. Previous studies have indicated
      that onset of seizures in the first years of life may be a risk factor for mental
      retardation, but the etiologies of the epilepsies were not included in the
      analyses. METHODS: Intellectual function was assessed at ages 2-20 years during
      presurgical evaluation in 100 patients with intractable epilepsy due to focal
      lesions limited to part of one lobe of the brain. Mental retardation (MR) was
      defined as Full-Scale Intelligence Quotient (FSIQ) < or =70. The age at seizure
      onset and the seizure frequency were obtained retrospectively. RESULTS: Younger
      ages at seizure onset were associated with lower FSIQ scores, and mean FSIQ was
      also significantly lower for patients with onset of epilepsy at < or =24 months
      of age (74.0 +/- 21.5) versus that in patients with onset of epilepsy later in
      life (87.8 +/- 18.8; p = 0.005). The frequency of patients with MR was
      significantly higher for patients with seizure onset at < or =24 months of age
      (15 of 33, 46%) than for patients with seizure onset later in life (eight of 67,
      12%; p < 0.001). This difference persisted within etiologic subgroups. For
      patients with focal malformation of cortical development, MR was seen in eight
      (50%) of 16 patients with seizure onset at < or =24 months versus two (10%) of 20
      patients with seizure onset at >24 months (p < 0.001); for patients with tumor,
      MR was seen in four (50%) of eight patients with seizure onset at < or =24 months
      versus four (13%) of 30 patients with seizure onset at >24 months (p = 0.003);
      and for patients with hippocampal sclerosis, MR was seen in two (28%) of seven
      patients with seizure onset at < or =24 months versus none of 30 patients with
      seizure onset at >24 months (NS). Within the subgroup with daily seizures, MR was
      present in 13 (65%) of 20 patients with seizure onset at < or =24 months versus
      five (17%) of 29 patients with seizure onset later in life (p = 0.001).
      CONCLUSIONS: These results indicate that onset of intractable epilepsy within the
      first 24 months of life is a significant risk factor for MR, especially if
      seizures occur daily. The risk based on early age at seizure onset appeared
      independent of etiology and persisted within subgroups of patients with focal
      malformation of cortical development, tumor, or hippocampal sclerosis.
      Prospective studies will be important to clarify whether early surgical
      intervention may reduce the risk for subsequent MR in carefully selected infants.

PMID- 11240602
TI  - Ictal perfusion changes during occipital lobe seizures in infancy: report of two
      serial ictal observations.
AB  - Serial-ictal single-photon-emission computed tomography (SPECT) examinations are
      presented in two infants (ages 1 and 2 years), with early ictal and ictal in one,
      and ictal and late ictal images in the other. Both had pharmacoresistant
      occipital epilepsy, due to focal cortical dysplasia. In the first case, size of
      ictal hyperperfusion increased in the course of the seizure from early ictal to
      ictal state. A concomitant ictal hypoperfusion was observed around the
      hyperperfused area. In the second patient, there was a dramatic difference
      between ictal and late ictal images. In the late ictal state, the previous
      occipital ictal hyperperfusion and extraoccipital ictal hypoperfusion
      disappeared, together with homolateral posterotemporal and contralateral
      occipital hyperperfusion, corresponding to seizure propagation. Ictal
      extratemporal blood-flow changes are therefore highly dynamic, particularly in
      very young children.

PMID- 11240604
TI  - ILAE Commission Report. Proposal for a new classification of outcome with respect
      to epileptic seizures following epilepsy surgery.

PMID- 11240603
TI  - Generalized convulsions after consuming a large amount of gingko nuts.
AB  - We report a 36-year-old woman, without any past or family histories of epilepsy,
      who presented frequent vomiting and generalized convulsions. About 4 h before the
      convulsion, she had consumed approximately 70-80 gingko nuts, seeds of Gingko
      biloba, in an attempt to improve her health. It is important to know that
      convulsion may be induced if a large amount of gingko nuts is consumed. The
      neurotoxicity of gingko nuts, particularly their convulsion-inducing effect,
      should be recognized.

PMID- 11240605
TI  - Cardiac arrest after fast intravenous infusion of phenytoin mistaken for
      fosphenytoin.

PMID- 11240606
TI  - Refractory idiopathic status epilepticus.

PMID- 11240607
TI  - Lactate and other metabolic changes in neuronal migration disorders.

PMID- 11240611
TI  - Making a therapeutic choice: human versus recombinant fractions - can we do it?
AB  - New manufacturing methods have resulted in production of higher purity human
      derived products and recombinant factors with less human- or animal-derived
      reagents or stabilizers for the treatment of congenital coagulation disorders. In
      addition, new viral inactivation processes are being used to reduce the chance of
      viral contamination. Preferred treatment approaches are moving toward using newer
      generation agents. At the same time, rationale exists for continuing
      fractionation of all types of products, based on considerations including cost,
      product availability, safety issues, and specific clinical situations for which a
      recombinant or high-purity product is not available. These issues and others are
      reviewed in the context of making a therapeutic choice.

PMID- 11240609
TI  - Long-term treatment retention with topiramate.

PMID- 11240612
TI  - The future of plasma-derived clotting factor concentrates.
AB  - In developed countries, preferred treatments for both haemophilia A and B have
      moved toward recombinant clotting factor concentrates, while plasma-derived
      replacement therapies are still required by many patients. Great improvements
      have been made in producing relatively pathogen-free clotting factor replacements
      from pooled plasma. The fluidity and complexity of the worldwide plasma product
      market are discussed in the context of the 'yin and yang' of plasma therapeutics,
      showing how multiple issues can influence the safety and availability of clotting
      factor concentrates. Use of plasma-derived products will likely continue for the
      next decade for patients with inhibitors, patients with von Willebrand disease,
      those requiring bypassing agents, in immune tolerance induction, and for
      treatment of rare inherited deficiencies of procoagulant or anticoagulant
      proteins. Furthermore, in developing countries many of the most advanced
      therapies are not available for the majority of haemophilia patients, and thus
      plasma-derived replacement concentrates will continue to be used even for
      noninhibitor patients.

PMID- 11240613
TI  - Use of ristocetin cofactor activity in the management of von Willebrand disease.
AB  - von Willebrand disease (vWD), the most common of the hereditary bleeding
      disorders, arises from quantitative or qualitative defects in von Willebrand
      factor (vWF). vWF is a multimeric plasma protein that plays a key role in primary
      and secondary haemostasis. In the current classification scheme, vWD is divided
      into six subtypes that are based on the nature of the vWF defect. Therapeutic
      strategies depend on the accurate identification of these subtypes. In most
      clinical situations, desmopressin is effective treatment for the great majority
      of patients with mild (type 1) disease, while replacement therapy with factor
      VIII/vWF concentrates that contain high levels of vWF activity is required for
      most type 2 and nearly all type 3 vWD patients. Several factor VIII/vWF
      replacement products are available, one of which (Humate P) has been approved for
      the treatment of vWD by the US Food and Drug Administration. Preliminary results
      of recent studies support the hypothesis that treatment with factor VIII/vWF
      concentrates based upon the content of vWF activity as reflected in the
      ristocetin cofactor assay is practicable, safe and efficacious. The establishment
      of optimal treatment regimens with respect to dose intensity and duration will
      require further study.

PMID- 11240614
TI  - Current therapy for rare factor deficiencies.
AB  - Haemophilia A and B and von Willebrand disease account for 80-85% of all
      inherited bleeding disorders. The other 15% are represented by deficiencies of
      fibrinogen, prothrombin, or factors V, VII, X, XI, or XIII. In addition, acquired
      factor deficiencies are seen in a variety of conditions ranging from malignancies
      to autoimmune disorders. The spectrum of symptoms in these conditions varies from
      severe and life-threatening haemorrhage to a mild bleeding diathesis. The
      diagnosis depends on demonstration of decreased activity of one of the clotting
      factors. Due to the rarity of each of the individual factor deficiencies,
      purified factor concentrates are not as readily available as they are for
      haemophilia A and B. Treatment of rare clotting factor deficiencies consists of
      the most purified blood product available that contains the missing factor.
      Depending on which factor is deficient, either purified concentrates, prothrombin
      complex concentrates, cryoprecipitate, or fresh frozen plasma can be used. In
      addition, recombinant factor VIIa is available for treating factor VII deficient
      patients.

PMID- 11240615
TI  - Gene therapy: a 2001 perspective.
AB  - In the past year, three clinical trials of gene therapy for haemophilia have been
      initiated. Years of preclinical studies have culminated in translation of
      research findings into the clinical arena. It is too early to predict which, if
      any, of these strategies will show efficacy. This paper will review basic aspects
      of gene therapy for haemophilia and will briefly outline current clinical trials.
      The three clinical trials all share a dose escalation design. The ongoing trial
      for haemophilia B involves the intramuscular administration of an adeno
      associated virus (AAV) vector expressing human factor IX. In preclinical studies,
      this strategy has produced therapeutic levels of circulating factor IX in
      haemophilic mice and dogs.

PMID- 11240616
TI  - New-generation recombinant factor concentrates: bridge to gene therapy.
AB  - Despite our best efforts to deceive the immune system, outwit pathogens, and
      improve upon the design of nature, there continues to be a need to improve the
      margin of safety of treatment for those with bleeding disorders. The current
      approach includes: (1) recombinant factor concentrates free of added proteins;
      (2) 'designer' factor molecules that enhance function and reduce immunogenicity;
      and (3) modulation of the immune system to suppress immune response in those who
      develop inhibitors. The hope is that through advances in our understanding of the
      coagulation and immune systems, treatment of haemophilia in the new millennium
      will be safer and less immunogenic. Currently available recombinant clotting
      factor concentrates include those produced: (1) with pasteurized human serum
      albumin in the cell culture medium as a stabilizer; (2) with bovine serum
      proteins in the cell culture medium; and (3) free of plasma derivatives. To the
      extent that current recombinant clotting factor concentrates contain even trace
      amounts of human or animal protein, there is continuing potential for
      transmission of nonenveloped viruses, including hepatitis A and parvovirus, and
      the theoretical potential for transmission of relatively unknown agents, such as
      prions (Creutzfeldt-Jakob disease or its variant). Second-generation recombinant
      factor concentrates that do not use human albumin as a stabilizer are currently
      in clinical trials, and third-generation recombinant factor concentrates
      currently in development take advantage of new strategies to achieve a 'protein
      free' cell culture, purification, and final formulation. It is likely that
      improvement in safety and reduction in immunogenicity will require modification
      not only of antigenic structure but also of the immune response to coagulation
      proteins.

PMID- 11240617
TI  - Characterization and mapping of resistance to Oidium lycopersicum in two
      Lycopersicon hirsutum accessions: evidence for close linkage of two Ol-genes on
      chromosome 6 of tomato.
AB  - The cultivated tomato is susceptible to powdery mildew (Oidium lycopersicum).
      Several accessions of wild species are resistant. In this study we describe (i)
      the genetics and mapping of resistance to O. lycopersicum in G1.1290, one of the
      resistant accessions in Lycopersicon hirsutum, (ii) fine mapping of Ol-1
      originated from L. hirsutum G1.1560, another resistant accession of L. hirsutum,
      and (iii) tests of allelism for resistance in G1.1290 and G1.1560. Initially, it
      is demonstrated that the resistance in G1.1290 to O. lycopersicum is controlled
      by an incompletely dominant gene, designated Ol-3. By using an advanced breeding
      line (ABL) containing introgression fragment(s) from G1.1290, Ol-3 was found to
      be associated with several RFLP and SCAR markers on chromosome 6. By using these
      markers, Ol-3 was mapped between markers TG25/SCAF10 and H9A11 on chromosome 6.
      Secondly, after testing some F3 lines and their progenies from the cross between
      L. esculentum cv Moneymaker and L. hirsutum G1.1560, we provided more evidence
      for the map position of Ol-1 to lie between SCAF10 and H9A11, indicating that Ol
      1 and Ol-3 are in the same chromosome region. Thirdly, although allelism tests
      could not discriminate between Ol-1 and Ol-3, (indirect) evidence suggested that
      these two genes are not identical. They might instead represent functional genes
      of a cluster of Ol-homologues.

PMID- 11240618
TI  - Genetic architecture of a wing size measure in Drosophila hibisci from two
      populations in eastern Australia.
AB  - Two models of evolutionary change invoke either additive genetic contributions to
      phenotypic traits (Fisher) or epistatic as well as additive effects (Wright). An
      earlier study of the flower-breeding Drosophila hibisci from two sites in eastern
      Australia reported additive and epistatic genetic effects as well as
      environmental effects on ovariole number. The present study of the same flies
      examines the genetic architecture of wing width, a trait that is correlated
      phenotypically with ovariole number and body size. A generation means analysis of
      flies reared at 25 degrees C indicated additive and epistatic genetic effects,
      but no consistent maternal effects, whereas for flies reared at three
      temperatures (18 degrees C, 21.5 degrees C, and 25 degrees C) linear and
      nonlinear environmental effects interacted with additive genetic effects. The
      genetic correlation matrix for ovariole number and wing width suggested negative
      genetic correlations between additive effects on one trait and epistatic effects
      on the other. Both traits provide evidence of genetic effects consistent with
      assumptions of Wright's shifting balance theory of evolution.

PMID- 11240619
TI  - Gene flow and selection balance in haplodiploid social insects.
AB  - Understanding the joint effects of gene flow and selection is one of the more
      important but difficult areas of evolutionary genetics. A method is presented to
      describe cases of gene flow-selection balance while accounting for the life
      history of haplodiploid social insects (eusocial Hymenoptera). A continent-island
      model is used to estimate gene flow rates from allele frequency data and provide
      variance formulae. The occurrence of unequal yet stable allele frequencies among
      social insect castes is explained and the usefulness of models with discrete
      generations for eusocial insects is explained. Gene flow and selection balance
      has been demonstrated for the fire ant Solenopsis invicta at two allozyme loci.
      This continent-island model gives results that well describe the system. Issues
      fundamental to the differences between X-linked and haplodiploid genetic systems
      and diploid genetic systems are also discussed.

PMID- 11240620
TI  - Coupling estimated effects of QTLs for physiological traits to a crop growth
      model: predicting yield variation among recombinant inbred lines in barley.
AB  - Advances in the use of molecular markers to elucidate the inheritance of
      quantitative traits enable the integration of genetic information on
      physiological traits into crop growth models. The objective of this study was to
      assess the ability of a crop growth model with QTL-based estimates of
      physiological input parameters to predict the yield of recombinant inbred lines
      (RILs) of barley. The model used predicts yield as spike biomass accumulated over
      the post-flowering period. We describe a two-stage procedure for predicting trait
      values from estimated additive and epistatic effects of QTLs. Values of
      physiological traits estimated by that procedure or measured in the field were
      used as input to the crop growth model. The output values (yield and shoot
      biomass) from the growth model using these two types of input values were highly
      correlated, indicating that QTL information can successfully replace measured
      input parameters. With the current crop growth model, however, both types of
      input values often resulted in large discrepancies between observed and predicted
      values. Improvement of performance may be achieved by incorporating physiological
      processes not yet included in the model. The prospects of using QTL-based
      predictions of model-input traits to identify new, high yielding barley genotypes
      are discussed.

PMID- 11240621
TI  - Effects of distance and pollen competition on gene flow in the wind-pollinated
      grass Festuca pratensis Huds.
AB  - Pollen dispersal and gene flow in the grass meadow fescue (Festuca pratensis
      Huds.) were studied using two populations which were homozygous for different
      allozymes at the Gpi-2 locus. The populations were established in a concentric
      donor-acceptor field experiment. Gene flow was found mainly to be affected by the
      distance between the donor and acceptor plants. Analysing 21 132 acceptor plant
      progenies, gene flow was shown to decrease rapidly with distance to the donor
      field up to 75 m, and beyond this distance much more slowly. The ability of donor
      pollen to fertilize acceptor plants depended very much on the density of the
      acceptor plants. Pairs of acceptor plants produced more compatible pollen
      locally, and captured significantly less donor pollen than single-plants. Despite
      the higher seed production of acceptor plants planted in pairs, the absolute
      number of heterozygous seeds carrying the donor allele was always lower than for
      single-plants. Wind direction had only a slight effect upon the type of pollen
      captured. Because of pollen production within the two plant populations being
      continuous and overlapping, the time when anthesis occurred had little effect on
      gene flow between the populations. Vigorous and tall acceptor plants with many
      panicles, high seed yield and high 1000-seed weight were able to capture more
      donor pollen than shorter plants. The results may be used to assess the risk of
      gene flow and to develop strategies for monitoring the spread of transgenes from
      genetically modified grasses.

PMID- 11240622
TI  - A hierarchical analysis of the genetic structure of an aquatic insect Bungona
      (Baetidae: Ephemeroptera).
AB  - Recent studies of the genetic structure of stream-dwelling organisms have
      suggested that fine-scale patterns are the consequence of patchy recruitment from
      a small number of matings and limited in-stream dispersal. Predictions of this
      hypothesis were tested by spatial and temporal analysis of the genetic structure
      of populations of a stream mayfly (Bungona sp: Baetidae) in subtropical streams
      in south-eastern Queensland. Significant departures from Hardy-Weinberg
      proportions occurred more often than would be predicted by chance alone and no
      consistent pattern was observed across sites, loci or sampling times. As in
      previous studies, the largest differentiation was observed at the smallest
      spatial scale (reaches within streams) on most sampling occasions. These data
      provide additional support for a patchy recruitment hypothesis. Despite the fine
      scale population structure, there was evidence of widespread adult dispersal
      across the study region, especially between streams and subcatchments within the
      same block of continuous dense forest.

PMID- 11240624
TI  - Frequency of insularia during the decline in melanics in the peppered moth Biston
      betularia in Britain.
AB  - Over the last three decades the frequency of the dark melanic form carbonaria of
      the peppered moth Biston betularia has declined in Britain. Data have been
      examined which show the intermediate phenotype insularia, controlled by alleles
      at the same locus, to have increased or remained level in frequency. Phenotype
      frequency of insularia does not always track allele frequency accurately because
      it is recessive to its alternative when carbonaria is common but dominant to the
      alternative when typical is common. It is shown that if insularia fitness lies
      between that of carbonaria and typical, and melanics replace typicals or vice
      versa, there will be a rise and fall in insularia allele frequency during a
      transitory period. The path followed is strongly affected by initial gene
      frequencies. During the high melanic period in Britain, differences in insularia
      frequency between localities may have been influenced by history of arrival of
      the novel morphs as well as by local selective conditions.

PMID- 11240625
TI  - Characterization of a hybrid zone between two chromosomal races of the weta
      Hemideina thoracica following a geologically recent volcanic eruption.
AB  - Two chromosomal races (2n=17 and 2n=15; XO) of the weta Hemideina thoracica meet
      at the centre of a volcanic region in North Island, New Zealand. Five independent
      polymorphic genetic markers showed broadly coinciding, steep frequency clines
      from north to south across this zone beside the flooded crater, Lake Taupo. Three
      unlinked nuclear gene markers provide estimates of zone width that are at least
      twice the width of the chromosomal and mitochondrial clines, with cline centres
      displaced at least 2.5 km. The different zone widths and centres suggest that
      this hybrid zone is a semipermeable barrier reducing the introgression of the
      chromosomal markers more than genic markers. We estimate that this species of
      weta must have a dispersal rate of at least 100 m per generation using the time
      since the last Taupo eruption (1850 years ago), which covered an area of about 20
      000 km2 with pyroclastic flow.

PMID- 11240623
TI  - Is there a geographical pattern in the breeding system of a complex of
      hermaphroditic slugs (Mollusca: Gastropoda: Carinarion)?
AB  - Allozyme analyses of the hermaphroditic slugs Arion (Carinarion) fasciatus, A.
      (C.) circumscriptus and A. (C.) silvaticus have suggested that the three species
      in North America and north-west Europe predominantly reproduce uniparentally,
      most probably by selfing. We used allozyme electrophoresis to investigate the
      population genetic structure of these species throughout a larger part of their
      native European distribution. Our results show that the previously reported
      "species" specific allozyme markers are no longer valid if populations from
      central Europe are investigated, and A. fasciatus and A. silvaticus appear to be
      "paraphyletic" taxa. In contrast to the general belief that selfing organisms
      show low gene diversities, the high selfing rates in N-NE European Carinarion do
      not necessarily result in low gene diversities. Moreover, our data suggest a
      geographical pattern in the prevalence of outcrossing, at least in A. fasciatus,
      with selfing in N-NE Europe and a mixed breeding system (i.e. selfing and
      outcrossing) in central Europe. Possible scenarios for the disjunct distribution
      of breeding systems in Carinarion are discussed.

PMID- 11240626
TI  - Quantitative genetics of life-history traits in a long-lived wild mammal.
AB  - Quantitative genetic studies of life-history traits in wild populations are very
      rare, yet variance/covariance estimates of these traits are crucial to
      understanding the evolution of reproductive strategies. We estimated
      heritabilities (h2) of several life-history traits (longevity, age and mass at
      primiparity, and reproductive traits) in two bighorn sheep (Ovis canadensis)
      populations, and both phenotypic (rP) and genetic (rA) correlations between life
      history traits in one population. We included adult mass in our analyses because
      it is related to several life-history traits. We used the mother-daughter
      regression method and resampling tests based on data from long-term monitoring of
      marked females. Contrary to the theoretical prediction of low heritability for
      fitness-related traits, heritability estimates in the Ram Mountain population
      ranged from 0.02 to 0.81 (mean of 0.52), and several were different from zero.
      Coefficients of variation tend to support the hypothesis of a higher
      environmental influence on life-history traits. In contrast, at Sheep River we
      found low heritabilities of life-history traits. Phenotypic correlations varied
      between -0.09 and 0.95. Several genetic correlations were strong, particularly
      for different reproductive traits that are functionally related, and ranged from 
      0.34 to 1.71. Overall, genetic and phenotypic correlations between the same
      variables were similar in magnitude and direction. We found no phenotypic or
      genetic correlations suggesting trade-offs among life-history traits. Bighorn
      sheep may not form the large, outbred populations at equilibrium that are assumed
      by both Fisher's fundamental theorem and by theories predicting antagonistic
      pleiotropy between life-history traits. Alternatively, the absence of negative
      genetic correlations may result from genetic variation in ability to acquire
      resources or from novel environmental conditions existing during the study
      period.

PMID- 11240627
TI  - Size-specific fecundity and the influence of lifetime size variation upon
      effective population size in Abies balsamea.
AB  - The hierarchy of plant size often present in dense populations of plants and the
      close correlation found between size and fecundity can result in an unequal
      distribution of fecundity, which reduces the ratio of effective population
      size/census number (Ne/N). Such an effect has been found previously in annuals,
      but no study has hitherto tested for the effect in the lifetime fecundity
      variation of a perennial population. We use the demographically stable size
      distribution to be found in natural, wave-regenerating populations of balsam fir,
      Abies balsamea, in order to estimate Ne/N. In both wave-regenerating and normal
      forests our estimated values of Ne/N were about twice those previously reported
      for annuals. We suggest that fecundity variance is expected to be smaller in
      trees and other long-lived perennials than in annuals because density-dependent
      mortality operates more strongly in the prereproductive phase of long-lived
      plants.

PMID- 11240628
TI  - Microsatellite analysis indicates genetic differentiation of the neo-sex
      chromosomes in Drosophila americana americana.
AB  - The neo-sex chromosomes of Drosophila americana americana were formed by a
      centric fusion between the autosomal element B and the X chromosome. Previous
      work has shown that the neo-Y chromosome is not degenerated genetically and that
      there is no evidence for genetic differentiation between neo-X and neo-Y
      chromosomes at the sequence level. To further address the genetic differentiation
      between the neo-sex chromosomes, microsatellites mapping to the neo-sex
      chromosome of D. a. americana were isolated. Microsatellite analysis indicated a
      highly significant differentiation between D. a. americana and D. a. texana as
      well as between the neo-X and neo-Y chromosomes in D. a. americana. Nevertheless,
      levels of variability were similar among the neo-sex chromosomes, indicating a
      very recent origin.

PMID- 11240629
TI  - Major histocompatibility complex (MHC) variation in the endangered Mexican wolf
      and related canids.
AB  - We have examined in Mexican wolves and related canids the amount of genetic
      variation for a class II gene in the major histocompatibility complex (MHC),
      thought to be part of the most important genetic basis for pathogen resistance in
      vertebrates. In Mexican wolves, descended from only seven founders over three
      lineages, there were five different alleles. These were in three phylogenetic
      groups, only one of which was shared between lineages. Using single stand
      conformation polymorphism (SSCP), we found that in samples of animals from the
      two polymorphic lineages, the observed heterozygosity was 0.74 and the genotypes
      were not different statistically from Hardy-Weinberg proportions. The Ghost Ranch
      lineage of Mexican wolves was monomorphic for the locus, consistent with the
      lower level of variation found previously for microsatellite loci and predicted
      from pedigree analysis. Samples of grey wolves, red wolves, and coyotes had 16
      additional alleles. One Mexican wolf allele was also found in grey wolves and
      another allele was shared between grey and red wolves. Most of the nucleotide
      variation resulted in amino acid variation and there were five different amino
      acids found at two different positions. Only two of the 21 variable amino acid
      positions had solely synonymous nucleotide variation. The average heterozygosity
      for eight individual amino acid positions in the Mexican wolves was greater than
      0.4. The estimated rate of nonsynonymous substitution was 2.5 times higher than
      that for synonymous substitution for the putative antigen binding site positions,
      indicative of positive selection acting on these positions. Examination of the
      known dog sequences for this locus showed that one of the Mexican wolf alleles
      was found in dogs and that the allele found in both grey and red wolves is also
      found in dogs.

PMID- 11240631
TI  - Distribution of genetic variation among chromosomal forms of Anopheles gambiae
      s.s: introgressive hybridization, adaptive inversions, or recent reproductive
      isolation?
AB  - A series of four papers in this issue explores the reproductive status of the
      five chromosomal forms of An. gambiae s.s. using molecular techniques to examine
      the variation among twelve different genes located throughout the An. gambiae
      s.s. genome. Results of these and previous studies are consistent with a
      hypothesis of at least partial barriers to gene flow between some chromosomal
      forms in the Ivory Coast and other West African countries to the north and west,
      but introgression between S and M types in Benin and countries to the east.
      Collectively, these studies indicate the need for a broader geographical sampling
      of An. gambiae s.s., increased research on mechanisms of prezygotic reproductive
      isolation and field-based studies of survival and fecundity in hybrids to test
      for postzygotic reproductive isolation.

PMID- 11240632
TI  - Molecular evidence of incipient speciation within Anopheles gambiae s.s. in West
      Africa.
AB  - We karyotyped and identified by polymerase chain reaction restriction fragment
      length polymorphism (PCR-RFLP) analysis Anopheles gambiae s.s. samples collected
      in several African countries. The data show the existence of two non-panmictic
      molecular forms, named S and M, whose distribution extended from forest to
      savannahs. Mosquitoes of the S and M forms are homosequential standard for
      chromosome-2 inversions in forest areas. In dry savannahs, S is characterized
      mainly by inversion polymorphisms typical of Savanna and Bamako chromosomal
      forms, while M shows chromosome-2 arrangements typical of Mopti and/or Savanna
      and/or Bissau, depending on its geographical origin. Chromosome-2 inversions
      therefore seem to be involved in ecotypic adaptation rather than in mate
      recognition systems. Strong support for the reproductive isolation of S and M in
      Ivory Coast comes from the observation that the kdr allele is found at high
      frequencies in S specimens and not at all in chromosomal identical M specimens.
      However, the kdr allele does not segregate with molecular forms in Benin.

PMID- 11240633
TI  - Molecular characterization of ribosomal DNA polymorphisms discriminating among
      chromosomal forms of Anopheles gambiae s.s.
AB  - The sequence of a 2.3 kb long DNA segment derived from the 5'-most end of the
      ribosomal intergenic spacer was determined in three chromosomal forms of
      Anopheles gambiae s.s. The analysis revealed that the sequence of the Mopti form
      differed from that of the Bamako and Savanna forms by a total of ten nucleotide
      substitutions. Using these sequence variations we set up a diagnostic polymerase
      chain reaction (PCR) assay to distinguish mosquitoes belonging to the three
      chromosomal forms, facilitating studies on the distribution and the ecology of
      these incipient taxa. The assay also allows to distinguish whether a given
      specimen could represent a heterozygote between Mopti and Savanna or Bamako.

PMID- 11240634
TI  - Attempts to molecularly distinguish cryptic taxa in Anopheles gambiae s.s.
AB  - Analyses of inversions in polytene chromosomes indicate that, in West Africa,
      Anopheles gambiae (sensu stricto) may be a complex of more than a single
      taxonomic unit, and these units have been called chromosomal forms. In order to
      determine whether this genetic discontinuity extends to the rest of the genome,
      as would be expected if reproductive isolation exists, we have sequenced several
      regions of both the nuclear and mitochondrial genomes. With one exception, we
      were unable to identify any nucleotide sites that differentiate the chromosomal
      forms. The exception was the internal transcribed spacer (ITS) of the ribosomal
      DNA (rDNA). Three sites in this region distinguish Mopti chromosomal form from
      Savanna and Bamako in Mali and Burkina Faso. However, outside these two
      countries, the association between chromosomal form and rDNA type does not always
      hold. Together with the variants in the rDNA intergenic spacer (IGS) described in
      the accompanying papers (della Torre et al., 2001; Favia et al., 2001), we can
      recognize two major types of rDNA, Type I and Type II (corresponding to molecular
      forms S and M in della Torre et al., 2001). Type I is widespread in West Africa
      and is the only type found outside of West Africa (i.e. Tanzania and Madagascar).
      Type II is confined to West Africa. We were unable to detect any heterozygosity
      for the ITS types even in five collections containing both types. A sample from
      the island of Sao Tome could not be classified into either Type I or Type II as
      the rDNA had characteristics of both. In general, our results confirm that An.
      gambiae is not a single pan-mictic unit, but exactly how to define any new taxa
      remains problematic. Finally, we have found minor variants of the major rDNA
      types fixed in local populations; contrary to most previous studies, this
      suggests restricted gene flow among populations of this species.

PMID- 11240637
TI  - Psyllid endosymbionts exhibit patterns of co-speciation with hosts and
      destabilizing substitutions in ribosomal RNA.
AB  - Eubacterial 16S rDNAs were sequenced from endosymbionts of seven psyllids
      (Psylloidea) and one whitefly (Aleyrodoidea), to investigate the evolution of
      endosymbionts and their hosts. Primary endosymbionts from all psyllids formed a
      highly supported clade, tentatively placed as the sister to whitefly primary
      endosymbionts, and showing several points of congruence with the host
      morphological phylogeny. Almost all host taxa yielded an additional eubacterial
      sequence, related either to known psyllid secondary endosymbionts or to other
      insect endosymbionts or parasites. The relationships of some secondary
      endosymbionts also suggested cospeciation with psyllid hosts, or ancient
      horizontal transfers. All primary endosymbionts, and some secondary
      endosymbionts, exhibited molecular genetic effects of a long-term, intracellular
      existence in their biased nucleotide content and decreased stability of rRNA
      secondary structure.

PMID- 11240636
TI  - Molecular characterization of two serine proteases expressed in gut tissue of the
      African trypanosome vector, Glossina morsitans morsitans.
AB  - Serine proteases are major insect gut enzymes involved in digestion of dietary
      proteins, and in addition they have been implicated in the process of pathogen
      establishment in several vector insects. The medically important vector, tsetse
      fly (Diptera:Glossinidiae), is involved in the transmission of African
      trypanosomes, which cause devastating diseases in animals and humans. Both the
      male and female tsetse can transmit trypanosomes and both are strict bloodfeeders
      throughout all stages of their development. Here, we describe the
      characterization of two putative serine protease-encoding genes, Glossina serine
      protease-1 (Gsp1) and Glossina serine protease-2 (Gsp2) from gut tissue. Both
      putative cDNA products represent prepro peptides with hydrophobic signal peptide
      sequences associated with their 5'-end terminus. The Gsp1 cDNA encodes a putative
      mature protein of 245 amino acids with a molecular mass of 26 428 Da, while the
      predicted size of the 228 amino acid mature peptide encoded by Gsp2 cDNA is 24
      573 Da. Both deduced peptides contain the Asp/His/Ser catalytic triad and the
      conserved residues surrounding it which are characteristic of serine proteases.
      In addition, both proteins have the six-conserved cysteine residues to form the
      three-cysteine bonds typically present in invertebrate serine proteases. Based on
      the presence of substrate specific residues, the Gsp1 gene encodes a chymotrypsin
      like protease while Gsp2 gene encodes for a protein with trypsin-like activity.
      Both proteins are encoded by few loci in tsetse genome, being present in one or
      two copies only. The mRNA expression levels for the genes do not vary extensively
      throughout the digestive cycle, and high levels of mRNAs can be readily detected
      in the gut tissue of newly emerged flies. The levels of trypsin and chymotrypsin
      activities in the gut lumen increase following blood feeding and change
      significantly in the gut cells throughout the digestion cycle. Hence, the
      regulation of expression for trypsin and chymotrypsin occurs at the post
      transcriptional level in tsetse. Both the coding sequences and patterns of
      expression of Gsp1 and Gsp2 genes are similar to the serine proteases that have
      been reported from the bloodfeeding insect Stomoxys calcitrans.

PMID- 11240635
TI  - Patterns of DNA sequence variation in chromosomally recognized taxa of Anopheles
      gambiae: evidence from rDNA and single-copy loci.
AB  - Patterns of DNA sequence variation in the ribosomal DNA (rDNA) second internal
      transcribed spacer (ITS2) and five unlinked single-copy nuclear loci were
      examined for evidence of reproductive isolation among four chromosomally
      recognized taxa of Anopheles gambiae from West Africa: Savanna, Bamako, Mopti and
      Forest, as well as sibling species An. arabiensis and An. merus. Included among
      the single-copy loci were three sequence-tagged random amplified polymorphic DNA
      (RAPD) loci, two of which (R15 and R37) had been reported as discriminating
      between Mopti and other chromosomal forms. Each of the five single-copy sequences
      were highly polymorphic in most samples. However, the R15 and R37 loci had no
      diagnostic value, and therefore are not recommended as tools in recognition of
      field-collected An. gambiae chromosomal forms. Although pairwise comparisons
      between species generally revealed significant levels of differentiation at all
      five loci, variation was not partitioned by chromosomal form within An. gambiae
      at any single-copy locus examined. The few exceptions to these trends appear
      related to a location either inside or nearby chromosomal inversions. At the
      tryptophan oxygenase locus inside inversion 2Rb, variation was structured only by
      inversion orientation and not by taxonomic designation even between An. gambiae
      and An. arabiensis, providing the first molecular evidence that the 2Rb inversion
      was transferred between species by introgressive hybridization. By contrast, the
      rDNA showed fixed differences between species and a difference diagnostic for
      Mopti, consistent with effective, if not complete, reproductive isolation. The
      apparent disagreement between the data from this locus and multiple single-copy
      loci within An. gambiae may be explained by the much lower effective population
      size of rDNA, owing to concerted evolution, which confers increased sensitivity
      at much shorter divergence times. Taken together with the accompanying reports by
      della Torre et al. (2001), Favia et al. (2001) and Gentile et al. (2001), our
      data suggest that neutral molecular markers may not have the sensitivity required
      to detect isolation between these recently established taxa.

PMID- 11240638
TI  - Characterization of genes expressed in the salivary glands of the tsetse fly,
      Glossina morsitans morsitans.
AB  - Salivary gland products of haematophogous insects including tsetse flies
      (Diptera: Glossinidia) are involved in antihaemostasis to allow for efficient
      blood feeding. In addition, salivary products of tsetse are thought to indirectly
      support the metacyclogenesis and eventual transmission of the African trypanosome
      protozoan parasites to their mammalian hosts. We have previously characterized
      the major anticoagulant, Tsetse Thrombin Inhibitor (TTI), from salivary extracts,
      and described molecular aspects of its cDNA from a Glossina morsitans morsitans
      salivary gland cDNA library. In addition, a family of two related genes with
      growth factor and adenosine-deaminase motifs (TSGF-1 and TSGF-2) have also been
      described. Here, we report on the molecular aspects of three different cDNAs and
      their putative products expressed in salivary glands: cDNAs TAg5, Tsal1 and
      Tsal2. The full-length transcript encoded by Tsetse Antigen 5 (TAg5) cDNA is 926
      bp excluding the poly(A) stretch, and has an open reading frame of 259 amino
      acids that can encode for a protein of 28 925 Da. The putative product of TAg5
      shows extensive similarities to cDNAs characterized from Drosophila (Agr and
      Agr2) and sandfly Lutzomyia (LuLoAG5). The cDNAs Tsal1 and Tsal2 are predicted to
      encode for mature proteins of 45 612 Da (399 amino acids) and 43 930 Da (389
      amino acids), respectively, and their putative products exhibit over 42% identity
      to one another. The N terminus of each putative protein contains a hydrophobic
      region with signal peptide characteristics indicating that they may be secretory
      in nature. Transcripts specific for TAg5 and Tsal2 genes can be detected in all
      developmental stages of tsetse while Tsal1 expression is limited to adult and
      larval stages. A reverse transcription polymerase chain reaction based
      amplification approach indicates that TAg5 transcipts can be detected from
      proventriculus and midgut tissues of the fly in addition to salivary glands,
      while Tsal1 and Tsal2 expression is restricted to salivary gland and
      proventriculus. The salivary glands of adult males are found to express higher
      levels of TAg5 and Tsal2 in comparison to females while no significant sex-based
      difference is observed for Tsal1 expression. The expression of these cDNAs in
      different tsetse species (G. m. morsitans, Glossina austeni and Glossina
      fuscipes) shows wide variations.

PMID- 11240639
TI  - The Drosophila gene Yippee reveals a novel family of putative zinc binding
      proteins highly conserved among eukaryotes.
AB  - An intracellular Drosophila protein, Yippee, was identified in a yeast
      interaction trap screen as physically interacting with Hyalophora cecropia
      Hemolin. The Yippee gene was isolated, structurally characterized, and mapped to
      the region 12A on the X-chromosome. Yippee contains a putative zinc-finger-like
      metal binding domain. It is the first characterized member of a conserved gene
      family of proteins present in diverse eukaryotic organisms, ranging from cellular
      slime mould to humans. A human cDNA clone was isolated and shown to be 76%
      identical to Drosophila Yippee. Yippee is ubiquitously expressed in different
      developmental stages of Drosophila and in different fetal tissues from human.
      Although the Hemolin-Yippee interaction remains to be further elucidated, the
      high degree of Yippee sequence conservation between a wide range of species
      suggests that this protein is of general importance in eukaryotes.

PMID- 11240640
TI  - Molecular cloning of a second prophenoloxidase cDNA from the mosquito Armigeres
      subalbatus: prophenoloxidase expression in blood-fed and microfilariae-inoculated
      mosquitoes.
AB  - Melanization constitutes an important component in various aspects of insect
      life, including cuticular sclerotization, egg-shell tanning, melanization of
      parasites and wound healing. Recently, a cDNA encoding prophenoloxidase (pro-PO),
      a key enzyme in the biosynthesis of melanotic material in insects, was cloned
      from microfilariae (mf)-inoculated mosquitoes, Armigeres subalbatus. However,
      results of Northern blot analyses indicated that two pro-POs might be present in
      Ar. subalbatus and these pro-POs might be responsible for two distinct
      physiological functions, egg-shell tanning and melanization of parasites.
      Subsequently, the second pro-PO cDNA (As-pro-PO II) was cloned from blood-fed Ar.
      subalbatus by rapid amplification of cDNA ends polymerase chain reaction. The
      2210 bp As-pro-PO II cDNA contains a 41 bp 5'-non-coding region, a 2064 bp open
      reading frame and a 105 bp 3'-non-coding region. A hydrophobic signal peptide for
      endoplasmic reticulum targeting is not found in the N-terminal region. The
      deduced amino acid sequence of As-pro-PO II shares a high degree of identity
      (81.5%) with that of the As-pro-PO I obtained from mf-inoculated Ar. subalbatus.
      Both Northern blot and reverse transcription polymerase chain reaction analysis
      demonstrated that these two mosquito pro-POs are persistently expressed in
      mosquito haemocytes and not in fat body, midgut, or ovaries. The expression of As
      pro-PO I and As-pro-PO II in mosquitoes is associated with melanization of mf and
      blood feeding, respectively.

PMID- 11240641
TI  - Molecular cloning of two prophenoloxidase genes from the mosquito Aedes aegypti.
AB  - The biosynthesis of melanotic materials is an important process in the life of a
      mosquito. Melanin production is critical for many diverse processes such as egg
      chorion tanning, cuticular sclerotization, and melanotic encapsulation of
      metazoan parasites. Prophenoloxidase plays a critical role in this biochemical
      cascade. Two cDNAs, one full length and one partial clone, and two genomic clones
      encoding prophenoloxidase (pro-PO) were isolated from the yellow fever mosquito,
      Aedes aegypti. The full-length cDNA, pAaProPO1, is 2286 bp long with a 2055 bp
      open reading frame encoding a 685 amino acid protein that shares 89% identity
      with Armigeres subalbatus pro-PO. It contains two putative copper binding domains
      (amino acids 197-243 and 346-423) that are homologous to other insect pro-POs.
      AaProPO1 messenger RNA (mRNA) was detected by reverse transcription polymerase
      chain reaction (RT-PCR) only from third-stage larvae and not in adult mosquitoes
      after blood feeding, during the melanotic encapsulation of Dirofilaria immitis
      microfilariae or following exposure to bacteria. A 750 bp fragment of the second
      cDNA (pAaProPO2) was cloned using RT-PCR from mRNA obtained from 14-day
      postovipostional eggs. AaProPO2 mRNA was not found in any other life stages, and
      may be in low abundance or transiently expressed. AaProPO2 and AaProPO1 each
      contain three introns that are 60, 68 and 58 bp and 61, 69 and 59 bp long,
      respectively, and the intron sequences of these two genes are not similar.

PMID- 11240642
TI  - The rate of terminal nucleotide loss from a telomere of the mosquito Anopheles
      gambiae.
AB  - Using a single copy pUChsneo transgene insertion at the Anopheles gambiae 2L
      telomere, this chromosome end was monitored by genomic Southern blots for forty
      four mosquito generations. During this time, the chromosome end lost terminal
      nucleotides at an apparently constant rate of 55 bp/generation, which can be
      accounted for by incomplete DNA replication and does not imply exonuclease
      activity. No telomere elongation events were detected, suggesting that a
      previously described gene conversion event at this transgene does not occur very
      frequently. Moreover, no evidence for elongation by transposable elements was
      found, as described in Drosophila melanogaster. These results are consistent with
      the proposal that gene conversion between complex terminal satellite repeats that
      are present at natural telomeres, represents the major telomere elongation
      mechanism in A. gambiae. Such recombination events between repetitive sequences
      would occur more frequently than between the single copy pUChsneo transgene on
      the 2L homologues.

PMID- 11240644
TI  - Parametrial resection for invasive cervical cancer.
AB  - Removal of the parametrium represents the greatest technical challenge and is the
      main source of treatment related morbidity during radical surgery for carcinoma
      of the cervix. The move away from radical en bloc strategies, seen in breast and
      vulvar cancer surgery, has not taken place in cervical cancer; rather an increase
      of radicality has been advocated. One important reason is uncertainty about the
      pattern of lymphatic drainage in the parametrium, in particular the existence or
      absence of parametrial lymph nodes. According to classic anatomic studies and
      more recent lymphangiographic studies, the parametrium is viewed as a lymph
      collecting trunk interposed between the organ of drainage (the cervix) and the
      regional nodes located on the pelvic wall. In contrast to this view, studies in
      cervical cancer patients using the giant section technique have reported nodes
      that may be involved early in spread of cervical cancer and which are distributed
      randomly throughout the parametrium. Based on this observation a strategy of
      uncompromised radicality regarding parametrial resection has evolved in
      preference to an individualized strategy with the degree of radicality tailored
      according to the need for safe margins around the central tumor. This review
      presents an overview of current knowledge about the parametrium and a discussion
      about decision making regarding parametrial resection in cervical cancer.

PMID- 11240645
TI  - Radiation treatment related factors influencing outcome in vulvar cancer
      patients.
AB  - The objective of this research is to identify the impact of radiation treatment
      factors on survival in vulvar cancer patients. We performed a follow-up study on
      60 women with squamous cell carcinoma of the vulva treated at the Department of
      Radiotherapy of the University of Ulm from 1980 to 1997. The follow-up time
      ranged from 0.5 to 17 years (mean 6.5 years). The irradiated volume included
      vulva and regional lymph nodes. The influence of treatment factors (tumor
      resection versus no tumor resection, treatment time, dose) on overall and disease
      free survival was examined. In addition, applied doses were corrected for
      treatment time using the extended alpha/beta-model for calculating the
      biologically effective doses. The applied dose was 48.1 +/- 13.2 Gy (median: 50
      Gy). Treatment time was 40.4 +/- 19.4 days (median: 38 days). 34/60 patients
      underwent surgery with complete resection of macroscopic tumor. 26 of 60 patients
      were resected incompletely or only a biopsy was taken. In univariate analysis
      prognostic factors influencing overall and disease-free survival were, along with
      T- and N-stage, treatment time, and biologically effective dose. In multivariate
      analysis, biologically effective dose was the only significant factor. We
      conclude that biologically effective dose and treatment time are important
      treatment factors influencing overall and disease-free survival vulvar cancer
      patients.

PMID- 11240646
TI  - Experience of a 2-day BEP regimen in postsurgical adjuvant chemotherapy of
      ovarian germ cell tumors.
AB  - The outcome of 31 patients with malignant ovarian germ cell tumors treated by
      surgery and a medium dose etoposide containing short chemotherapy regimen between
      1988 and 1997 is reported. Of the 31 patients, 16 (51.6%) had malignant
      teratomas, 8 (25.8%) had dysgerminomas, 6 (19%) endodermal sinus tumors and one
      (3.2%) mixed germ cell tumor. Twenty-four (77.4%) patients were at FIGO stage I
      (of which 18 were stage IA), 2 (6.5%) at stage II, 4 (12.9%) at stage III and 1
      (3.2%) at stage IV. Twenty-five (80.6%) patients underwent conservative surgery,
      1 (3.2%) underwent bilateral salpingo-oophorectomy and 4 (12.9%) had total
      hysterectomy with bilateral salpingo-oophorectomy and omentectomy. One (3.2%)
      patient refused definitive treatment. Three patients with stage IA grade 1
      immature teratomas were not treated with adjuvant chemotherapy and one patient
      with a stage IA dysgerminoma refused chemotherapy. Two patients with endodermal
      sinus tumor returned to their countries of origin after surgery. Twenty-five
      patients received bleomycin, etoposide, and cisplatin (BEP) regimen with
      etoposide dosage fixed at 120 mg/m2 on day 1 and day 2, bleomycin 15 mg
      intravenous bolus on days 1 and 2 and cisplatin 100 mg/m2 on day 1. Chemotherapy
      was administered at four weekly intervals for 4 cycles or until complete response
      was achieved. The median number of cycles of chemotherapy was four (range 3-6)
      for stage I, 6 (range 4-7) for stage II and 5 (range 5-6) for stage III tumors.
      Of the entire cohort of 29 patients analyzed, the median follow up period was 5
      years. One patient died from stage IIIC endodermal sinus tumor and one patient
      had persistent teratoma in the lungs. The overall disease free survival control
      rate was 93.1%. There were three cases of the growing teratoma syndrome involving
      the liver, abdominal peritoneum, and the pelvis, respectively. No mortality
      resulted from the growing teratomas. No pulmonary complications, secondary
      primary tumor or leukemia was detected. Menstrual function returned in all
      patients with fertility-preserving surgery and one pregnancy occurred. This
      interesting data suggest that a medium dose 2-day BEP postsurgical adjuvant
      chemotherapy regimen is effective and superior to expectant treatment of
      malignant ovarian germ cell tumors. This report, however, should be viewed as a
      pilot study. The result indicates that a prospective randomised controlled trial
      to demonstrate equivalence of this regimen with the standard BEP regimen is
      warranted.

PMID- 11240647
TI  - G-CSF receptor expression in ovarian cancer.
AB  - Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is clinically
      used to overcome neutropenic periods during chemotherapy. In vitro studies using
      cell lines as a model system have recently suggested that G-CSF can promote
      ovarian cancer growth. The objective of this work is to determine whether tumor
      cells express G-CSF-receptors (G-CSFR). A set of ovarian tumor biopsies and
      ovarian cancer cell lines was analyzed by RT-PCR, immunohistochemistry and
      immunofluorescence. The presence of a 276 bp-amplicon (exon 8-10) obtained by RT
      PCR showed that 12 out of 16 ovarian tumor biopsies and two out of four ovarian
      cancer cell lines expressed G-CSFR-mRNA. G-CSFR-protein was detected in tumor
      cells of the 12 biopsies that also contained G-CSFR-mRNA. A second 409 bp
      amplicon (exon 17) obtained by RT-PCR from the variable C-terminal cytoplasmic
      region of G-CSFR could be amplified only in four out of 16 biopsies and in none
      of the ovarian cancer cell lines studied. The results presented here indicate
      that G-CSFR is frequently expressed in ovarian cancer cells. Moreover, the
      failure of RT-PCR amplification of the 409 bp-amplicon in samples that express G
      CSFR-mRNA suggests that C-terminal truncated receptor forms are also expressed.

PMID- 11240648
TI  - The false negative rate of cervical smears in high risk HIV seropositive and
      seronegative women.
AB  - We undertook a prospective study of cytology and concurrent colposcopically
      directed biopsies of both Human Immunodeficiencey Virus seronegative (HIV-) and
      seropositive (HIV +) women at high risk for cervical intraepithelial neoplasia
      (CIN) to determine the accuracy of Pap smears in this population. Women were
      recruited from a sexually transmitted disease clinic and a women's prison in
      eastern Massachusetts. All were interviewed, blood was tested for HIV with CD4
      counts done in 101 of the 102 HIV + women, and all received a pelvic exam that
      included a conventional Pap smear, a Thinprep test, and colposcopy with directed
      biopsies and endocervical curettage. A total of 184 women volunteered. 82 were
      HIV- and 102 were HIV+. The prevalence of CIN in HIV+ women was 37%, more than
      twice the 17% prevalence of CIN in HIV-women (P = 0.002). When Atypical Squamous
      Cells of Undetermined Significance (ASCUS) findings were included with "negative"
      cytology, the conventional Pap smear false negative rates for HIV- and HIV+ women
      were 21% and 37%, respectively. When ASCUS was included with "positive" cytology,
      the false negative rates dropped to 14.3% for HIV- women and 10.5% for HIV+
      women. We conclude that ASCUS diagnoses comprised the majority of false negatives
      in HIV+ women.

PMID- 11240649
TI  - Cytokines IL-1beta, IL-2, IL-6, IL-8, MCP-1, GM-CSF and TNFalpha in patients with
      epithelial ovarian cancer and their relationship to treatment with paclitaxel.
AB  - In vitro work suggests that cytokines may be important modulators of the
      cytotoxic effects of paclitaxel and subsequent drug resistance. This has been
      investigated in vivo in patients with ovarian cancer by ELISA. There was
      consistently elevated expression of IL-6 and IL-8 but not MCP-1, IL-1beta, IL-2,
      GM-CSF or TNFalpha. Peritoneal fluid concentrations of IL-6, IL-8 and MCP-1 were
      two to three logs greater than serum concentrations. Elevated concentrations of
      IL-6 correlated with a poor final outcome (P = 0.039), and increased IL-6 and IL
      8 correlated with a poor initial response to chemotherapy (P = 0.041 and P =
      0.041, respectively). There was a relatively clear pattern of change in all three
      cytokines. In serum, IL-6, IL-8 and MCP-1 decreased with the administration of
      steroids prior to paclitaxel, and increased in the 24 h after paclitaxel.
      Postoperative drainage fluid was relatively acellular, preventing flow-cytometric
      analysis of epithelial cells for apoptosis, but suggested activation of T cells
      by paclitaxel. IL-6 and IL-8 appear to be of prognostic importance in epithelial
      ovarian cancer. Treatment with paclitaxel is associated with an increase in
      expression of a limited number of cytokines in patients with ovarian cancer,
      notably IL-6, IL-8 and MCP-1.

PMID- 11240650
TI  - Early invasive (FIGO stage IA) carcinoma of the cervix: a clinico-pathologic
      study of 476 cases.
AB  - The clinical and histologic features of 476 tumors fitting the 1995 FIGO
      definition of stage IA cervical cancer, treated at a Sydney tertiary referral
      hospital between 1953 and 1992, are reviewed. Five-year follow-up was complete
      with a median of 10 years. The diagnosis was increasingly made by histologic
      examination of colposcopically directed cone biopsy. The majority (88%) of tumors
      were squamous. The proportion of both younger women (</=35 years) and
      adenocarcinoma and adenosquamous tumors increased during the second half of the
      study. Nearly half invaded 1 mm; a third 1.1-3 mm and 20% 3.1-5 mm. Lymph
      vascular space invasion (LVSI) increased with increasing depth of invasion and
      was present in over half the tumors invading >3 mm. Treatment was surgical in 99%
      and was increasingly more conservative as the study progressed with no apparent
      increase in treatment failure. From 1973 treatment by cone biopsy rose from 6.5
      to 35%, by radical hysterectomy fell from 51 to 21% and by lymphadenectomy from
      53 to 26%. Only one of 115 patients treated by cone biopsy died. Positive lymph
      nodes were detected in 1.7% of 180 patients undergoing lymphadenectomy. There
      were 16 recurrences (3.4%); six vaginal with no cancer deaths, nine pelvic and
      one distant, with nine deaths and three new cancers (two deaths). Univariate
      analysis suggests that older age, glandular tumors and those invading 3 mm were
      associated with more treatment failures and multivariate analysis showed that
      both conservative hysterectomy and the omission of lymphadenectomy are associated
      with higher recurrence rates with >3 mm invasion. The study failed to resolve the
      dilemma of predicting those tumors with a poor prognosis.

PMID- 11240651
TI  - Neoadjuvant chemotherapy with cisplatin, ifosfamide and 5-fluorouracil in the
      treatment of locally advanced cervical cancer.
AB  - The objective of this study was to evaluate clinical and histological response,
      resectability, and survival in patients with cervical epidermoid carcinoma stage
      IB2 to IIIB with the use of neoadjuvant chemotherapy followed by radical surgery
      and/or radiation therapy. Between September 1989 and February 1996, 53 patients
      were admitted to this study. They were given three cycles of cisplatin 30
      mg/m2/day, 5-fluorouracil 500 mg/m2/day, ifosfamide 2000 mg/m2/day i.v., and
      mesna 400 mg/m2/day i.v. at hour 0 and 400 mg/m2 at hours 4 and 8 during three
      days every 21-28 days. We evaluated 47 patients. Global clinical response
      obtained was 85% {95% (CI), 75-97%, CR in 14 patients (30%) and PR in 26 patients
      (55%)}. Twenty-three patients underwent surgery. Six patients (13%) had a
      complete histological response. Median follow-up was 42 months (5-96). In
      resected patients, with a median follow-up of 57 months (5-96), the estimated
      five-year disease-free survival was 78%. Global survival estimated to 60 months
      was 83% for stage IB2, 70% for IIB, and 20% for IIIB. This mode of therapy offers
      a new option to improve survival in locally advanced cervical cancer. Randomized
      trials are required in order to establish a definitive role for this therapeutic
      strategy.

PMID- 11240652
TI  - Prospective multicenter study on urologic complications after radical surgery
      with or without radiotherapy in the treatment of stage IB-IIA cervical cancer.
AB  - A national collaborative group has conducted a multicenter prospective study on
      the use of a specific glossary for the complications associated with the
      treatment of cervical cancer, which were analytically described in 1989. This
      report analyzes the urologic complications with particular reference to radical
      surgery in stage IB-IIA cancer cases. In the prospective multicenter clinical
      study 2024 patients with frankly invasive cervical cancer were enrolled (IB =
      1041; IIA = 308; IIB = 384; IIIA-B = 237; IV = 54). This report considers 1349
      patients with stage IB-IIA disease. Treatment modalities in this group of
      patients were: type III radical surgery in 21.9%; type III radical surgery
      followed by radiotherapy in 20.8%; type III radical surgery preceded by
      radiotherapy in 7.3%; type II radical surgery in 3.1%; type II radical surgery
      followed by radiotherapy in 8.4%; type II radical surgery preceded by
      radiotherapy in 18.8%; surgery plus chemotherapy plus radiotherapy in 3.5%;
      radiotherapy alone in 16%. In this case series 873 complications were registered,
      and among these 341 (39.1%) were described in the urinary tract. Among 277
      bladder complications 47.3% were grade 1; 47.3% grade 2, and 5.4% grade 3. Among
      64 ureter complications 59.4% were grade 1; 17.2% grade 2, and 23.4% grade 3.
      Distribution of severe urinary complications was different according to site
      (bladder or ureter) and treatment modalities (radical surgery alone: bladder
      1.3%, ureter 1.3%; radical surgery followed by radiotherapy: 1.4% bladder, 2.8%
      ureter; radical surgery preceded by radiotherapy: 3% bladder, 0% ureter).
      Different distributions of severe urinary complication were also observed in
      respect to stage (IB vs IIA); treatment: elective vs nonelective. In 673 patients
      treated with radical surgery plus or minus radiotherapy 123 relapses were
      registered (18.2%). Incidence of relapse was not different in patients suffering
      from mild/severe complications vs patients without complications. Disease-free
      survival, death from tumor, and death from other causes were not different in the
      group with complications in comparison to the group without complications.

PMID- 11240653
TI  - Reduced immunologic cell performance as a prognostic parameter for advanced
      cervical cancer.
AB  - The proliferative response of lymphocytes to mitogens is known to be decreased in
      cancer patients; this phenomenon is thought to play an important role in disease
      progression, but it has not been studied as a prognostic factor in cervical
      cancer patients receiving treatment. Fourteen patients with advanced cervical
      cancer submitted to chemotherapy with cis-platinum (100 mg/m2/cycle) and
      bleomycin (30 mg/cycle) over three cycles every 4 weeks were evaluated. Mean
      follow-up time was 30 months. The following laboratory tests carried out on
      peripheral blood lymphocytes collected before and at the end of chemotherapy were
      used as prognostic factors: proliferative response of lymphocytes to
      phytohemagglutinin (PHA) and stimulated with interleukin 12 (IL-12), capacity of
      gamma interferon production (IFN-gamma), and variations in memory T cell (CD45
      RO) and naive T cell (CD45-RA) subsets. A clear correlation was obtained between
      response to treatment, survival rates, and PHA-induced proliferative response. A
      significant difference was observed in the number of CD45-RO lymphocyte at the
      pre-chemotherapy period and IFN-gamma production at the post-chemotherapy period
      in the group of good responders to treatment. The use of IL-12 produced a
      leveling in both groups for lymphocyte proliferation, i.e., a recovery from the
      deficiency presented by the lymphocyte of the poor responders group. The
      parameters of immunologic assays, especially proliferative response, appears to
      be correlated with prognosis and survival rates and therefore are good
      discriminating factors for the selection of groups of patients that will benefit
      from this type of treatment. IL-12 seems to play an important role in the
      regulation of the antitumor immune response and should be considered for
      therapeutic use.

PMID- 11240654
TI  - Adaptative intima fibrosis in blood vessels in cervical carcinomas after
      preoperative cytotoxic chemotherapy.
AB  - Angiogenesis is an important component of tumor growth. After preoperative
      cytotoxic chemotherapy, tumor blood vessels of a large caliber become
      increasingly tortuous and their lumens narrow. The narrowing of the vessel lumens
      results from fibrosis of the intimal layer, which is called adaptative intimal
      fibrosis (AIF). We describe AIF in three patients with cervical cancer after a
      complete or partial response to preoperative cytotoxic chemotherapy. Two patients
      with no residual disease in the surgical specimen had severe AIF and are free of
      disease at 12 and 124 months. The patient with residual disease had only moderate
      AIF and developed a recurrence. AIF has not been described in cervical cancer.
      Our findings suggest that AIF may be a morphologic correlate of tumor regression
      following preoperative cytotoxic chemotherapy.

PMID- 11240655
TI  - Triplet pregnancy with hydatidiform mole.
AB  - Multiple pregnancies with hydatidiform mole are rare. We describe here a patient
      who delivered a male fetus and a female fetus together with molar tissue
      following treatment for infertility. comparing microsatellite polymorphisms in
      the DNA from the patient, her partner, the two normal placentas and the molar
      tissue, we were able to show that this was a triplet pregnancy with two normal
      conceptions and a complete hydatidiform mole of monospermic origin.

PMID- 11240656
TI  - Ovarian carcinoma, pericardial metastasis and human immunodeficiency virus
      infection.
AB  - As the AIDS epidemic increases at an alarming proportion, there is a greater
      likelihood of finding gynecological malignancies in HIV-positive females. The
      clinician is therefore faced with management and ethical dilemmas, as the most
      appropriate management in this setting is unknown. This case report illustrates
      both an unusual site of pericardial metastasis in a patient with HIV infection
      and ovarian carcinoma. The management of the pericardial tamponade is also
      described.

PMID- 11240657
TI  - Workshop Report: Combining the staging system of the International Federation of
      Gynecology and Obstetrics with the scoring system of the World Heath Organization
      for Trophoblastic Neoplasia. Report of the Working Committee of the International
      Society for the Study of Trophoblastic Disease and the International Gynecologic
      Cancer Society.
AB  - During the past 5 years the International Society for the Study of Trophoblastic
      Disease and the International Gynecological Cancer Society have moved to modify
      the staging system for trophoblastic disease by combining the staging of the
      International Federation of Gynecology and Obstetrics (FIGO) with the scoring
      system of the World Health Organization (WHO). By making significant changes in
      both, the classification will be more acceptable worldwide leading to uniform use
      by physicians reporting management results in trophoblastic disease. This is the
      report of the Rome Workshop, which will be presented for ratification to the FIGO
      Staging Committee in September 2000.

PMID- 11240658
TI  - Diagnosis and treatment delay in gynecological malignancies. Does it affect
      outcome?
AB  - Delay of diagnosis and treatment of malignant tumors is perceived as unfavorably
      affecting outcome. However, tumor behavior may be determined early in the
      histogenesis process and the outcome may be more a function of the biologic
      properties of the tumor than of our ability to make an early diagnosis. The
      objective of the present review is to evaluate data concerning the effect of
      diagnosis and treatment delay on outcome in gynecological malignancies. A medline
      search including the terms diagnosis delay, treatment delay, outcome, vulvar
      carcinoma, cervical carcinoma, endometrial carcinoma and ovarian carcinoma was
      conducted and all pertinent articles in the English language were included.
      Relatively few investigations deal with the effect of diagnosis and treatment
      delay on prognostic factors and on outcome in invasive gynecological
      malignancies. The reviewed data do not seem to indicate an unequivocal
      deleterious effect of a delay of several weeks or even several months in patients
      with some gynecological malignancies. Intentional delay of diagnosis or treatment
      of gynecologic malignancies is unjustified; however, the data presented should
      encourage a closer scrutiny and possibly a revision of the concept of "early"
      diagnosis and of the notion that delay of any duration has a definite,
      unfavorable effect on outcome.

PMID- 11240659
TI  - Squamous carcinoma of the uterine cervix with CIN 3-like growth pattern: An under
      diagnosed lesion.
AB  - Invasive squamous carcinomas of the cervix have traditionally been classified
      into keratinizing, non-keratinizing, verrucous, warty (condylomatous), papillary
      transitional (squamo-transitional), and lymphoepithelioma-like carcinomas. The
      majority of these tumors are easily recognized. We present for the first time the
      pathological appearances of six cases of invasive squamous carcinoma with growth
      pattern simulating tangentially cut CIN 3 involving endocervical glandular
      crypts/clefts. In all cases initial diagnosis on biopsy and/or loop excision was
      thought to be CIN 3, perhaps with suspicion of early invasion. On further
      excision and/or on clinical grounds the tumors were frankly invasive. We propose
      the use of the term squamous carcinoma with "CIN 3-like growth pattern" for such
      lesions. This is in order to avoid misinterpretation as CIN 3 with subsequent
      inappropriate management of patients with this type of tumor.

PMID- 11240660
TI  - A comparison of the ERBE Erbotom ICC 200 generator and the Valleylab Force 2
      electrosurgical generator in performing large loop excision of the transformation
      zone.
AB  - One drawback of the large loop excision of the transformation zone procedure
      (LLETZ) is the influence of electrical current on histological interpretation
      through thermal artefact. The ERBE Erbotom ICC 200 unit (Surgical Technology
      Group, Hampshire, England, UK) compared to other standard electrosurgical
      generators has the theoretical advantage that it automatically regulates the
      output according to "demand" and therefore uses the minimum amount of power to
      complete the procedure, which thus should cause the minimum thermal artefact.
      Fifty females requiring the loop procedure were randomized to treatment with
      either the ERBE machine or the standard Valleylab electrosurgical generator.
      Although there were no significant differences in the diathermy artefact
      measurements between the two groups, the Valleylab unit was associated with more
      mucosal destruction or removal (P = 0.027) and an increased number of specimens
      uninterpretable due to diathermy artefact. The new technology associated with the
      ERBE unit had clear benefits for the clinician in terms of the time of the
      procedure and technical problems.

PMID- 11240661
TI  - Emergence of cisplatin-resistant cells from the OVCAR-3 ovarian carcinoma cell
      line with p53 mutations, altered tumorigenicity, and increased apoptotic
      sensitivity to p53 gene replacement.
AB  - Resistance to chemotherapy commonly compromises the treatment of many advanced
      cancers. Evidence suggests a correlation between chemoresistance and more
      aggressive tumor growth, possibly through accumulation of additional genetic
      defects in drug-treated or resistant cells. To study this process in a human
      ovarian cancer model, we examined OVCAR-3 cells for acute sensitivity to
      cisplatin (cDDP) and subsequent emergence of drug-resistant clones following
      chronic cDDP exposure. Clonal cells (OVCAR-3/C-1) that displayed 20-fold reduced
      sensitivity to cisplatin but retained equivalent sensitivity to paclitaxel, as
      compared with the parental population, were isolated. The cDDP-resistant clone
      had growth kinetics similar to those of parental population, but when
      transplanted into the peritoneal cavity of nude mice, they acquired the ability
      to grow with the development of both ascites and solid tumor masses; such growth
      was not detectable after transplantation of the drug-sensitive parental cell
      line. C-1 cells had a p53 gene mutation (codon 266) that was not detected in the
      parental OVCAR-3 cell line, and infection of C-1 cells with p53-adenovirus (rAd
      p53) caused greater apoptosis and gene transduction than that observed in the
      similarly infected parental population. rAd-p53 induced high levels of p21WAF1,
      p27Kip1, activated caspase 3 and apoptosis in C-1 cells, without causing major
      changes in bax or bcl-XL levels. Together, the results suggest that alterations
      in tumor growth and gene mutations characterize cDDP-resistance in OVCAR-3 cells,
      and viral replacement of one of these defective genes (p53) may provide an
      effective treatment for elimination of drug-resistant cells.

PMID- 11240662
TI  - Phantom metastases in trophoblastic disease.
AB  - Trophoblastic disease occasionally presents with apparent metastases that turn
      out to be lesions not associated with the trophoblastic tumor. In this article,
      we present one case of a cerebellar hemangioma, two of lung and mediastinal
      teratoma, and one of pulmonary granuloma masquerading as metastases from
      trophoblastic disease. If an apparent metastasis associated with trophoblastic
      tumor does not accord with the clinical diagnosis, look for an independent cause.

PMID- 11240663
TI  - p53 as a significant prognostic marker in endometrial carcinoma.
AB  - Although several studies have reported that p53 overexpression is associated with
      poor survival from endometrial cancer, this relationship might be confounded by a
      number of possible factors. The objective of this study was to examine the
      prognostic role of p53 overexpression in endometrial cancer when a panel of well
      selected potential confounding factors were controlled. One hundred and twenty
      five endometrial cancers were examined for p53 overexpression by
      immunohistochemistry (IHC). Demographic and clinical data, including age at
      diagnosis, race, residence, tumor grade, surgical stage, and other possible
      confounding factors for endometrial cancer such as diabetes, family history of
      cancer, hypertension, hormone replacement therapy (HRT), and obesity were
      collected from medical charts and pathologic reports. Survival status was
      determined at the end of follow-up. The Kaplan-Meier method was used to derive
      the survival curve, while the log-rank test was used to compare curves for two or
      more groups of patients. The proportional hazards regression model was used to
      obtain maximum likelihood estimates of relative risks (RR) and their 95%
      confidence intervals. Compared to the p53 nonaltered group, the presence of p53
      overexpression in endometrial carcinoma was related to significantly decreased
      patient survival. High nuclear grade and high FIGO stage were associated with
      poor survival. No obvious association was found between survival and study site,
      race, age, and other potential risk factors of endometrial cancer. Only two
      variables (p53 and stage) were significantly associated with poor survival in the
      multivariate proportional hazards analysis. Overexpression of p53 was found to be
      the most significant predictor of specific survival. The relative risk for p53
      overexpression was 7.46 (95% CI: 4.26-13.1) and for late stage was 4.35 (95% CI:
      1.91-9.92). We conclude that p53 overexpression is the most important predictor
      for patient survival when a panel of well-selected potential confounding factors
      are taken into account. Patients with endometrial cancers who have p53
      overexpression have a seven-fold higher risk of dying from disease compared to
      those without p53 overexpression. Whether detection of p53 alteration may serve
      as an indicator of high-risk patients for whom more aggressive adjuvant
      chemotherapy may be considered needs to be explored in the future.

PMID- 11240664
TI  - Exon deletions and variants of human estrogen receptor mRNA in endometrial
      hyperplasia and adenocarcinoma.
AB  - Estrogen receptors (estrogen receptor alpha, ER) belong to a family of ligand
      modulated transcription factors that play an important role in the progression of
      such tumors as breast and endometrial cancers. Functional domains, a set of
      mutations and variants produced by internal deletions of ER mRNA, have mainly
      been identified in breast cancer. Experimental results suggest that the presence
      of variants may result in different proteins which differ in activity and
      modulate the ER signaling pathway differently. We analyzed samples from 21 cases
      of endometrial hyperplasia and from 29 cases of endometrial cancer for the
      presence of internal exons and exon deletion variants of ER mRNA. ER and
      progesterone receptor (PgR) proteins were measured using Western blot technique
      in all endometrial cancer samples. We found that absence of the wild-type exon
      PCR product of ER mRNA in a sample increased in parallel with malignant potential
      in both sample types, whereas the number of exon deletion variants detected in
      the same sample decreased in cases of malignancy. The precise deletions of the
      respective exons suggest that they are probably the result of splicing errors. A
      relatively high number of variants in hyperplasia samples may indicate the
      important role of ER mRNA variants in the physiologic regulation of transcription
      in estrogen-sensitive genes. Eleven of 29 adenocarcinomas expressed a 62-kDa ER
      protein, truncated at the amino terminal, whereas all but one sample expressed a
      short 52 kDa variant ER protein. Our results suggest that differing ER proteins
      are generally present in human endometrial adenocarcinomas and that they may
      influence the estradiol signaling pathways.

PMID- 11240665
TI  - Predicting response to neoadjuvant chemotherapy in patients with cervical
      carcinoma: can we do without any longer?
AB  - The aim of the study was to identify variables that may predict the response to
      neoadjuvant chemotherapy (NACT) in patients with cervical cancer as maturing data
      from the literature indicate that this therapeutic strategy might be beneficial
      to some but harmful to others. Clinico-pathologic variables including age,
      histology, tumor differentiation, as well as immunohistochemical overexpression
      of p53, mdm2, c-erbB-2, and cathepsin D in 37 of these patients were evaluated as
      possible predictors of response to the NACT. Fifty-five patients with stage IIB
      cervical cancer submitted to two courses of cisplatin/ifosfamide/mesna prior to
      definitive treatment with radical surgery or radiation therapy were the subjects
      of this study. The clinical response rate was 80% but none of the variables was
      able to predict response to NACT. Unless methods are found enabling us to predict
      response and therefore to identify those patients that could benefit from
      including NACT in the treatment of locally advanced cervical cancer, only women
      with primarily resectable tumors should be selected for this multimodality
      approach as a result of the possibility of cross-resistance with radiation
      therapy in nonresponders.

PMID- 11240666
TI  - The use of human papillomavirus typing in detection of cervical neoplasia in
      Recife (Brazil).
AB  - High risk types of human papillomavirus (HR-HPV) play a major role in cervical
      cancer oncogenesis. This study aims to evaluate the efficacy of HPV detection and
      typing as a means of identifying cervical neoplasia in a high risk population. A
      management algorithm for implementation of HPV detection in clinical practice is
      also proposed. A nested case-control within a cohort study was undertaken in
      Recife (Brazil). All 479 participants had cervical scrapes collected for HPV
      detection followed by colposcopy. Samples were blindly analyzed by polymerase
      chain reaction (PCR) and typed by restriction fragment length polymorphism
      (RFLP). HPV detection by PCR and typing with RFLP cost US$ 4.92 per woman
      screened in this study and is significantly better than cytology in identifying
      women at risk of developing cervical cancer (P = 0.0001). Women who tested
      positive for HR-HPV had over 35-fold increased risk of having high grade squamous
      intraepithelial lesion (HSIL) or cervical cancer, although this does not
      necessarily translate into the same risk rate for women with latent HPV infection
      developing major cervical neoplasia. HPV typing offers 90% sensitivity and 85%
      specificity for cervical cancer detection. In combination with cytology it
      provides a negative predictive value of 99.4% and a sensitivity of over 96% for
      detection of HSIL and cervical cancer. We conclude that HPV typing is an
      inexpensive and effective method for identification of cervical neoplasia and
      women at risk of developing it. It improves quality control for both false
      negative and false positive cytology results. Routine screening intervals could
      safely be increased to 3-5 years, decreasing anxiety and socio-economic
      inconveniences.

PMID- 11240667
TI  - Concentration of vascular endothelial growth factor (VEGF) and transforming
      growth factor-beta1 (TGF-beta1) in the serum of patients with cervical cancer:
      prediction of response.
AB  - The aim of this study was to determine the value of the measurement of serum VEGF
      and TGF-beta1 levels in the diagnosis of cervical cancer and to see whether these
      levels decrease after treatment for cervical cancer. We measured serum VEGF and
      TGF-beta1 levels through EIA in patients with CIN (n = 35), and cervical squamous
      cell cancer (n = 48). We also measured serum VEGF, TGF-beta1, and SCC antigen
      levels before and after radiotherapy in 13 cervical squamous cell cancer
      patients. The sizes of the tumors in those patients were measured by a computer
      tomography scan or magnetic resonance imaging. The serum VEGF levels were
      different between CIN and cervical cancer groups (P < 0.1), and the serum TGF
      beta 1 levels in the cervical cancer group were lower than those in the other
      groups (P < 0.05). The serum VEGF levels were significantly related to the serum
      TGF-beta 1 levels in the cervical cancer patients (P < 0.01). In the cervical
      cancer patients, the decrease in the circulating VEGF levels after receiving
      radiotherapy was related to the decrease in tumor size (P < 0.01). While the
      measurement of serum VEGF level is adjuvant in diagnosing cervical cancers,
      serial serum VEGF level measurements may find a clinical use in the follow-up of
      women treated for cervical cancer.

PMID- 11240669
TI  - Chemo-resistant choriocarcinoma cured by pulmonary lobectomy and craniotomy.
AB  - This is a case report of a 31 year-old female with choriocarcinomatous metastasis
      in brain and lung. Her serum beta-HCG level rose six times following
      normalization during 61 months of diverse multiagent systemic chemotherapy.
      Pulmonary lobectomy was done in March 1997 (57 months after initial diagnosis)
      due to persistent pulmonary nodule and poor response to chemotherapy. Histologic
      examination disclosed metastatic choriocarcinoma. However, her serum beta-HCG
      level did not normalize. Meanwhile, repeated measurement of beta-HCG
      concentration in cerebrospinal fluid was normal and imaging studies did not
      indicate evidence of metastasis. Sixty-one months after initial diagnosis
      fulminant intracerebral hemorrhage made emergency craniotomy mandatory.
      Histologic examination revealed metastatic choriocarcinoma. Serum beta-HCG levels
      returned to normal immediately after craniotomy and she reached complete
      remission after whole brain irradiation in January 2000. She is free of disease
      91 months from initial diagnosis. The role of surgery in the treatment of
      patients with metastatic choriocarcinoma has been diminished by the
      responsiveness to chemotherapy. However, local resection of metastases still
      seems to play a significant role in controlling complications of gestational
      trophoblastic neoplasia and even in curing the disease in a small subset of
      patients.

PMID- 11240668
TI  - Regulation of cell growth and HPV genes by exogenous estrogen in cervical cancer
      cells.
AB  - Human papillomavirus (HPV) infection is known as the major cause of the
      development of cervical cancer. The E6 and E7 proteins of oncogenic HPV can play
      critical roles in immortalization and malignant transformation of cervical
      epithelial cells. From the previous epidemiologic data, it has been determined
      that long-term use of oral contraceptives may be a risk factor for cervical
      cancer. Investigation of the estrogenic and antiestrogenic effects on the
      proliferation of cervical cancer cells and the gene expression of HPV would help
      to explain the role of estrogen in the HPV-associated pathogenesis of cervical
      cancer. In this study, cervical cancer cells (HeLa, CaSki, and C33A) were
      cultured in vitro in the presence of 17beta-estradiol or tamoxifen to observe
      their regulatory growth effect and HPV E6/E7 gene expression. The estrogenic
      effect on the promoter activity of HPV URR was further confirmed by transient
      transfection assay, which was conducted in C33A cells using the HPV-18 URR-CAT
      reporter plasmid. The supplemental effect of estrogen receptors on URR promoter
      activity was also evaluated. The proliferation of HeLa and CaSki cells was
      stimulated by estradiol at physiologic concentration levels (</=1 x 10-6 M). At a
      low concentration (0.1 x 10-6 M), tamoxifen also stimulated the proliferation of
      HeLa and CaSki cells. In contrast to HPV-positive cervical cells, the
      proliferation of C33A was not influenced by exogenous estradiol or tamoxifen,
      indicating that HPV might play a role in the hormonal stimulation of cell growth.
      Interestingly, the proliferation of HeLa was markedly suppressed at high
      concentrations of estradiol and tamoxifen (5 and 10 x 10-6 M). The levels of HPV
      18 E6 and E7 mRNA were significantly increased by estradiol at a concentration of
      0.5 x 10-6 M. Transient transfection experiments using the HPV URR-CAT reporter
      plasmid in C33A cells indicated that the expression of HPV E6/E7 genes was
      increased by the treatment of estradiol and tamoxifen. Co-transfection of
      estrogen receptors (ER) and URR-CAT leads to a fourfold increase in CAT activity
      by estradiol or tamoxifen at physiologic concentrations. When estradiol or
      tamoxifen was administered at high concentrations (5 x 10-6 M), a DNA ladder,
      typically indicative of apoptosis, was observed in HeLa cells. In conclusion,
      estradiol stimulated the growth of HPV-positive cervical cancer cells, as did
      tamoxifen at low concentrations (0.1 x 10-6 M). The growth stimulation of HPV
      positive cervical cancer cells by estrogen appeared to be related to the
      increased expression of HPV E6/E7. Growth suppression observed at high
      concentrations of estradiol and tamoxifen in HeLa cells might be a result of
      apoptosis. Taken together, these data suggested that exogenous estradiol might be
      a risk factor in HPV-mediated cervical carcinogenesis.

PMID- 11240670
TI  - A case of clear cell carcinoma arising in extragonadal endometriosis.
AB  - Malignancy developing in extragonadal endometriosis is rare with the majority of
      cases being endometrioid adenocarcinomas. We present a 54-year-old woman who
      developed a clear cell carcinoma in her perineum, 25 years after excision of a
      perineal endometrioma in an episiotomy scar. Treatment involved radiotherapy and
      surgery, with a view to preserving vaginal function. Where benign extragonadal
      endometriosis occurs, the potential for malignant transformation persists even
      years after primary treatment.

PMID- 11240671
TI  - Regarding ligation of the hypogastric artery and blood loss.

PMID- 11240672
TI  - PRESIDENTIAL ADDRESS: Gynecological oncology in the new millennium.

PMID- 11240673
TI  - The management of borderline epithelial tumors of the ovary.
AB  - The histopathological diagnosis and treatment of borderline epithelial tumors of
      the ovary (BTO) still pose problems to both pathologists and gynecologists. BTO
      is a disease of younger, fertile females and generally has an excellent
      prognosis. A minority of patients, however, succumb to this disease. A review of
      the literature is given addressing aspects of epidemiology, histology, treatment
      and prognosis, resulting in a proposal for the management of serous and mucinous
      borderline tumors of the ovary.

PMID- 11240674
TI  - Interval cervical cancer following treatment for cervical intraepithelial
      neoplasia.
AB  - The objective of this study was to determine whether those women who developed
      cervical cancer following treatment for preinvasive disease had common features
      in their history which could identify those at increased risk of progression and
      therefore be used to modify management protocols. A retrospective case note
      review from clinical and histopathologic records was undertaken at a teaching
      hospital in Wessex, Southern England. The review included 33 women diagnosed with
      cervical carcinoma between 1985 and 1996 who had previously undergone treatment
      for cervical intraepithelial neoplasia (CIN) or cervical glandular
      intraepithelial neoplasia (CGIN). The diagnosis prior to treatment was CIN 3 in
      19 cases, CGIN 3 in 2 cases, CIN 2 in 9 cases (97% high grade CIN/CGIN) and CIN 1
      in 1 case. At primary treatment, among those treated by knife cone biopsy or
      Large Loop Excision of the Transformation Zone (LLETZ), and for whom the margins
      of the treatment specimen were reported, 14 out of 15 had incomplete margins.
      Local ablation (in which completeness of excision could not be histologically
      assessed) was performed in 12 cases. In 58% (19/33) of cases, the patient was 40
      years or older at the time of initial treatment. Fifteen women had one or more
      negative smears after treatment, of which only 6 had transformation zone
      sampling. The interval between treatment of CIN/CGIN and diagnosis of invasion
      ranged from 8 to 216 months. (mean 40.4 months), with 67% of cases of invasive
      cancer occurring within 5 years of treatment for CIN/CGIN and 94% within 10
      years. Screen detection was achieved in 91% (30/33) of cases with 53% diagnosed
      while stage 1A. In conclusion, most treatment screen detection of invasive
      disease at an early (and often microinvasive) stage was achieved for most
      patients, although a third of patients were diagnosed more than 5 years after
      initial treatment. The data suggest the need to follow up longer than 5 years
      when there are risk factors such as incomplete excision of high grade CIN/CGIN
      and in women over 40 years of age at the time of initial diagnosis.

PMID- 11240675
TI  - Cyfra 21-1 marker in carcinoma of the cervix.
AB  - Cyfra 21-1 has been reported to be an effective tumor marker for epithelial
      carcinomas. The purpose of this investigation was to determine its value in
      evaluating response to treatment in patients with carcinoma of the cervix. Cyfra
      21-1 levels were measured by immunoassay in the serum of 55 untreated patients
      with cervical cancer; a second sample was obtained in all of them after
      conventional treatment for association with clinical response. Pre-therapy levels
      were elevated in only 45% (25 of 55) of the patients, with a slight tendency to
      increase according to clinical stage: 33% (5/15) in stage I, 36% (8/22) in stage
      II and 67% (12/18) in stage III. In regards to association with response to
      therapy, and including patients with either normal or elevated pretreatment
      values, 46% (19/41) of women with a complete clinical response either persisted
      with or developed elevated levels after treatment completion. All 14 patients
      with persistent disease after therapy continued to have or developed elevated
      values. No patient with persistent disease had normal values after therapy, and
      all patients with negative values after treatment were truly complete clinical
      responders. The results of our study suggest that the test has a low sensitivity
      therefore and, despite our findings, a negative level after treatment may not be
      a safe indicator of disease-free status. On the other hand, an elevated post
      treatment level is not a reliable indicator of persistence, proven by the fact
      that 46% of clinical responders fell in this category. Therefore, Cyfra 21-1 has
      a very limited role in correlating with response to treatment in carcinoma of the
      cervix.

PMID- 11240676
TI  - A phase II trial of mitomycin, ifosfamide and cisplatin in recurrent carcinoma of
      the cervix.
AB  - The purpose of this study was to evaluate the efficacy and the toxicity of
      mitomycin, ifosfamide, and cisplatin in patients with recurrent carcinoma of the
      cervix. Between July 1992 and March 1995, 20 patients with recurrent cervical
      cancer were enrolled in this study. No patients had received prior chemotherapy
      for metastatic disease, except some were exposed to cisplatin as a
      radiosensitizer at the time of their diagnosis. Mitomycin-C 6 mg/m2, ifosfamide 3
      g/m2, and cisplatin 50 mg/m2 were given intravenously every 3 weeks. All patients
      were assessible for response and toxicity, and none was lost to follow-up. All
      patients except one had squamous cell carcinoma. The overall response rate was
      45% (2 complete remissions and 7 partial remissions). The mean response duration
      was 35 months, and the median survival from treatment for the whole group was 14
      months. Fifteen percent of all cycles produced grade 3 or 4 myelosuppression, and
      the main nonhematologic toxicity was nausea and vomiting, which was reported in
      11.5% of all cycles. One death occurred secondary to chemotherapy-induced
      septicemia. Three patients are still alive, two with a complete response and one
      with a partial response. In conclusion, mitomycin, ifosfamide, and cisplatin have
      a good activity in recurrent carcinoma of the cervix and are comparable to other
      combination chemotherapy.

PMID- 11240677
TI  - Prognostic factors in young women with endometrial carcinoma: a report of 20
      cases and review of literature.
AB  - We retrospectively reviewed the pathologic features of patients with endometrial
      carcinoma (EC) treated in our facility between 1989 and 1998. First, we
      identified the clincopathologic features of young women with EC and compared them
      with similar patients from the literature. Second, 148 EC patients were divided
      into two groups: group A (age</=45 years, n = 20) and B (age>45, n = 128). The
      mean follow-up periods were 65 months and 50 months in groups A and B,
      respectively. Group A patients had better disease-free survival (Kaplan-Meier
      method, P = 0.0283) compared to group B patients. The independent variables
      related to disease-free survival (Cox regression analysis) were age (P = 0.0001),
      stage (P = 0.0183), histology (P = 0.0011), and lymph node metastasis (P =
      0.0007). The distribution of stage was significantly different between the two
      groups (Chi-square test, P = 0.0089). More group A patients (18 of 20; 90%) had
      early stage disease. There were no significant differences (Fisher's exact test)
      between the two groups in histology, grade, cervical involvement, vascular
      invasion, tumor size, ovarian malignancy, and lymph node metastasis. However,
      group A patients had a significant higher incidence of disease confined to the
      inner half of the myometrium than group B patients (P = 0.0004). We statistically
      confirmed that young women with EC had better outcome due to a significantly
      higher proportion of early stage disease and less myometrial invasion than older
      patients.

PMID- 11240678
TI  - Contemporary experience with the management of vulvar intraepithelial neoplasia.
AB  - Experience with 40 cases of vulvar intraepithelial neoplasia seen during the 7
      year period 1992-98 is detailed. The average age was 46.2 years and 27 of the
      patients (67.5%) were aged 50 years or younger. There was a significant
      association with cigarette smoking when compared with age-matched control
      patients attending the Vulvar Clinic with non-neoplastic conditions (67.5 vs.
      12.5%; P = 0.001). Twenty-five percent of the patients had a past history of
      cervical intraepithelial neoplasia (CIN). The disease was multifocal in 77.5% of
      patients-92.6% of women aged less than 50 years and 53.8% of older women (P =
      0.014). Treatment was by surgical excision supplemented in some cases by laser
      ablation. Occult stromal invasion was detected histologically in 15% of cases and
      in half of these, the invasion was to a depth considered to have significant
      metastatic potential. Recurrence occurred in 50% of patients and was more common
      in patients with multifocal disease. One patient (2.5%), aged 30, developed
      invasive vulvar carcinoma 4 years after treatment.

PMID- 11240679
TI  - The effect of being overweight on survival in endometrioid carcinoma of the
      endometrium at different ages.
AB  - The effect of being overweight on survival in endometrioid carcinoma of the
      endometrium was examined at different ages in this article. The body mass index
      [body weight/height(m2)] was evaluated in 287 Japanese women with endometrioid
      carcinoma. Overweight individuals were defined as those with a body mass index of
      24.5 or more. The subjects were divided into two groups, including a younger age
      group (women less than 50 years of age) and an older age group (women 50 years of
      age or more). Being overweight was thus analyzed to see if it had any influence
      on survival. The body mass index ranged from 15 to 40 (mean +/- SD; 23.0 +/-
      3.9). Twenty-six (32.1%) of 81 subjects in the younger age group and 78 (37.9%)
      of 206 subjects in the older age group were found to be overweight. In the
      younger age group, we could find no effect of being overweight on survival. In
      the older age group, the cumulative 10-year survival rate was 75.2% in normal
      weight subjects and 89.4% in overweight subjects (P < 0.02). However, the
      histologic grade, depth of myometrial invasion, cervical invasion, lymphovascular
      invasion, ovarian metastases, and lymph node metastases showed no significant
      difference between normal weight and overweight subjects in both the younger and
      older age groups. In a multivariate analysis, being overweight was a better
      independent prognostic factor in older age group. Being overweight may contribute
      to the heterogenous etiology of endometrioid carcinomas in the older age group.

PMID- 11240680
TI  - The morbidity of surgery and adjuvant radiotherapy in the management of
      endometrial carcinoma.
AB  - A retrospective review of side effects and complications of treatment in 522
      patients with endometrial cancer managed in a gyneoncology unit was conducted.
      This study evaluated 517 patients who underwent total abdominal hysterectomy and
      bilateral salpingo-oophorectomy (TAH BSO). Lymphadendectomy or lymph node
      sampling was performed with the primary surgery in 264 and 41 cases,
      respectively. Postoperative radiotherapy was given as external beam or vault
      brachytherapy. Serious morbidity included lymphedema, hemorrhage, and vaginal
      stenosis. Lymphadenectomy was associated with lymphedema and lymphocyst formation
      in 11% of the cases. Vascular injury associated with lymphadenectomy occurred in
      0.7% of the cases; however, this was satisfactorily managed through adequate
      surgical training and experience by staff within the unit. The incidence of
      vaginal stenosis (54.7%) following postoperative vault brachytherapy was a
      particular concern for clinical follow-up and sexual function. Although many
      women were not sexually active prior to treatment, those who were had high levels
      of sexual dysfunction, even when vaginal stenosis was not present.

PMID- 11240681
TI  - Radiotherapy and radical surgery for treatment of patients with bulky stage IB
      and II cervical carcinoma.
AB  - The aim of this study was to evaluate prognostic factors and to study combination
      radiotherapy-surgery as treatment for patients with bulky stage Ib and II
      cervical carcinoma. From 1985 to 1994, 187 patients with cervical cancer >/= 4
      cm, were treated by combined radiation therapy and radical surgery including
      systematic para-aortic lymphadenectomy. Complications were observed in 34 (18%)
      patients. In a multivariate analysis, young age, tumor size less than 5 cm,
      metastatic nodes with capsular rupture, and bilateral nodes were independent
      prognostic factors. Overall survival at 3 years was 85%, 56%, and 40% in patients
      with negative nodes, positive pelvic nodes, and positive para-aortic nodes,
      respectively (P < 0.001). These results confirm the prognostic significance of
      young age, tumor size, and nodal involvement. Radical surgery combined with
      radiotherapy is feasible, with an acceptable rate of complications and yields
      satisfactory survival results in patients with bulky stage IB and II cervical
      carcinoma. Recent randomized published studies have demonstrated that concomitant
      chemotherapy and radiotherapy should be the gold standard in this setting. The
      role of surgery is questioned.

PMID- 11240682
TI  - Acceptance of voluntary HIV testing and the prevalence of HIV infection in women
      with cervical neoplasia in Toronto.
AB  - Over a 13-month period (1998-99), 661 adult women under the age of 50 years with
      a diagnosis of high grade squamous intraepithelial lesions (HSIL) or invasive
      cervical cancer in the previous 5 years and who were unaware of their HIV status
      were approached to participate in this study. After pretest counseling, patients
      completed a short questionnaire about risk factors for HIV infection, had blood
      samples drawn for HIV testing,and arranged a follow-up appointment for test
      results and post-test counseling. The acceptance rate for HIV testing was 73% (N
      = 432 with HSIL and N = 51 with invasive cervical cancer). Most women reported
      heterosexual intercourse as their only risk factor for HIV infection, with the
      majority (95.1%) reporting more than one lifetime sexual partner. Women who
      declined participation were significantly older (P < 0.01) than participants and
      nonwhites were more likely to decline (P < 0.001). None of the study participants
      had positive HIV test results (0/483; 95% CI, 0.00-0.009). Although HIV testing
      was accepted by most women following pretest counseling, there were no women who
      tested HIV-positive who were previously unaware of their status. Consequently we
      do not recommend routine HIV testing in this population.

PMID- 11240683
TI  - Uterine papillary serous carcinoma following radiation therapy for carcinoma of
      cervix: a case report.
AB  - Uterine papillary serous carcinoma (UPSC) is a clinically aggressive and
      morphologically distinctive variant of endometrial carcinoma that has been
      recognized recently as a distinct entity. The association between radiation
      therapy (RT) and UPSC is rarely described in the literature. We describe the
      clinicopathologic features of a 71-year-old patient with UPSC that developed 15
      years after radiation therapy for squamous cell carcinoma of cervix, stage IIB.
      In the subtotal hysterectomy specimen the endometrium was irregular with
      multifocally raised masses. Microscopically, the tumor was composed of high-grade
      papillary serous carcinoma focally admixed with solid transitional cell
      carcinomatous areas and multifocal intraepithelial carcinoma in adjacent atrophic
      endometrium. The tumor exhibited diffuse infiltrative growth with frequent
      lymphatic tumor emboli in the myometrium. Immunohistochemical staining for p53
      and c-erbB-2 were positive in about 70% of the tumor cells. Carcinoembryonic
      antigen (CEA) was focally positive. Ki-67 positive cells were present in about
      60% of the tumor cells. The tumor directly extended to the cervix and perirectal
      soft tissue and metastasized to the omentum. Intraoperative pelvic washing
      cytology was positive for papillary adenocarinoma cells. The possible etiologic
      role of radiation is discussed, and the literature on endometrial carcinomas
      developing after RT is reviewed.

PMID- 11240684
TI  - Aggressive endometriosis: report of a case.
AB  - A 54-year-old premenopausal woman presented with abdominal pain, constipation,
      and raised serum CA-125 levels during routine follow-up of a low-grade
      endometrial stromal sarcoma with prominent sex cord-like features, which had been
      treated by vaginal hysterectomy 4 years previously. The findings at laparotomy
      included: a 100-mm unilocular thick-walled right ovarian cyst, a solid 25-mm
      nodule in the left meso-ovarium, and a phlegmonous mass in the wall of the
      sigmoid colon, which proved to be a pericolic abscess due to diverticular
      disease. The ovarian cyst was a histologically benign endometrioid cystadenoma
      with stromal luteinization in the wall. Small islands of morphologically benign
      endometrial tissue were present in vessels of the meso-ovarium. The left adnexal
      nodule exhibited florid morphologically benign endometriosis, much of which was
      within and occluding large vascular spaces, and of apparently recent onset. No
      lesions resembled, in any way, the original stromal sarcoma. There was no
      evidence of endometriosis elsewhere in the pelvis or abdomen. The patient has
      made an uneventful recovery and is being monitored, as before, by tumor markers
      only. The discordance in morphology between the uterine sarcoma and the
      subsequent pelvic lesions was so complete as to raise doubts about any
      pathogenetic relationship between them. We propose the use of the term aggressive
      endometriosis to describe the changes observed.

PMID- 11240685
TI  - Disruption of cell cycle control by human papillomaviruses with special reference
      to cervical carcinoma.
AB  - Human papillomaviruses (HPVs) play a major role in neoplastic transformation of
      squamous epithelial cells. The viral genome is small in size and only encodes a
      limited number of proteins, so one of the major functions of the viral proteins
      is to modulate the function of key cellular proteins involved in cell cycle
      control and DNA replication. During this process important host cell cycle
      checkpoints are lost which may lead to the accumulation of genetic abnormalities
      and eventual malignant transformation. This review briefly describes the normal
      cell cycle and also the mechanisms by which HPVs interfere with cell cycle
      control both as part of their productive life cycle and in the process of
      neoplastic transformation.

PMID- 11240687
TI  - Uterine carcinosarcomas in patients receiving tamoxifen. A report of 19 cases.
AB  - Uterine carcinosarcomas are highly aggressive neoplasms with a tendency to early
      extrauterine spread, high stage at diagnosis, and a poor prognosis. Tamoxifen is
      widely used as adjuvant therapy in the treatment of breast cancer and is known to
      cause endometrial proliferative lesions, including adenocarcinoma. In recent
      years, there have been occasional reports of uterine carcinosarcoma in patients
      taking tamoxifen. The aim of this study is to describe the clinicopathologic
      profile in 19 women taking tamoxifen who subsequently developed uterine
      carcinosarcoma. Nineteen patients were identified from cases of uterine
      carcinosarcoma diagnosed at three institutions. The case notes were examined and
      the pathology reviewed. The age at diagnosis of carcinosarcoma ranged from 47 to
      91 years (mean 71 years). All patients were postmenopausal and received 20 mg
      tamoxifen daily; the duration of treatment ranged from 1 to 15 years (mean 7.1
      years). The cumulative dose of tamoxifen ranged from 7.3 to 109.5 g. Ten tumors
      were stage I, one stage II, seven stage III, and one stage IV. Ten of the
      carcinosarcomas were homologous, and nine contained heterologous elements in the
      form of rhabdomyoblasts (six cases) or malignant cartilage (three cases). The
      overall prognosis was extremely poor. Fifteen patients died within 35 months of
      the diagnosis of carcinosarcoma (mean 12 months). Two patients are alive with
      very short follow-up periods, and two were lost to follow-up. The reported data
      support an association between tamoxifen therapy and the development of uterine
      carcinosarcoma. The risk is likely to be highest in those patients who have been
      taking tamoxifen for a prolonged period. A majority of tumors in the present
      study were stage I, and this suggests that uterine carcinosarcomas in patients
      taking tamoxifen may be diagnosed at an earlier stage than those arising de novo.
      However, the prognosis was still poor even with low-stage disease. Properly
      controlled epidemiological studies are necessary to confirm an association
      between tamoxifen and uterine carcinosarcoma.

PMID- 11240686
TI  - Impact of hysteroscopy on disease-free survival in clinically stage I endometrial
      cancer patients.
AB  - Recent data strongly suggest tumor cell dissemination of endometrial carcinoma
      cells in the course of fluid hysteroscopy. In patients who had endometrial cancer
      which was (except for peritoneal cytology) confined to the uterus, the disease
      free survival (DFS) of 135 patients who underwent hysteroscopy prior to staging
      laparotomy was compared with the DFS of 127 patients without hysteroscopy. After
      a median follow-up of 23 months, 10 patients experienced tumor recurrence.
      Although there was a trend towards a higher incidence of positive peritoneal
      cytology at laparotomy in patients who underwent hysteroscopy, this difference
      did not achieve statistical significance (P = 0.47). For 5 years, the DFS was
      92.4% in patients with hysteroscopy and 84.7% in patients without hysteroscopy
      before laparotomy (log-rank, P = 0.782). Our data therefore suggest a similar
      short-term DFS in endometrial cancer patients with and without hysteroscopy prior
      to laparotomy.

PMID- 11240688
TI  - Topotecan for recurrent cervical cancer after platinum-based therapy.
AB  - The activity and toxicity of topotecan in women with recurrent cervical cancer
      are described from a case series of women with recurrent cervical cancer who had
      measurable disease and were not amenable to cure by surgery or radiation. All
      patients had prior platinum-based chemotherapy and developed progressive disease.
      Topotecan was given as 1 mg/m2/day over 30 min for 5 days every 3 weeks until
      progression of disease or prohibitive toxicity. Between July 1998 and July 1999,
      12 patients received a total of 20 cycles of topotecan. Median age was 41 years
      (range 21-62), and 11 (92%) patients had prior whole pelvic radiation. The mean
      number of topotecan cycles was 1.5 (median 1, range 1-3). There were two partial
      responses (16.7%; 95% CI, 2% to 48%), both in prior radiation fields. Five
      patients required red blood cell transfusions, four had grade II nausea and
      vomiting, two developed sepsis (one with neutropenia), one developed fever, and
      one reported hyperpigmentation. There were no treatment-related mortalities.
      Although topotecan appears to exhibit modest activity in recurrent cervical
      cancer after radiation and platinum-based therapy, bone marrow toxicity may limit
      the utility of this regimen without hematopoietic growth factor support.

PMID- 11240689
TI  - BRCA1 and BRCA2 mutations in ovarian cancer: Covariation with specific
      cytogenetic features.
AB  - We analyzed 37 primary invasive carcinomas for BRCA1 and BRCA2 mutations by
      screening the entire coding regions of both genes. Seven predicted truncating
      mutations (four in BRCA1 and three in BRCA2) and one novel BRCA1 missense variant
      (S1542C) were identified (8/37, 22%). Two of the BRCA1 mutations were somatic
      changes, whereas the remaining three BRCA1 changes and all mutations of BRCA2
      were found to be of germline origin. All eight BRCA-positive tumors were serous
      or seropapillary carcinomas (8/27 serous tumors, 30%), and all but one were
      poorly differentiated. The correlation between tumor karyotype and BRCA status
      showed that clonal chromosomal aberrations were present in all BRCA-positive
      tumors (8/8) compared with 20 of 29 BRCA-negative ones. The most consistently
      affected region in BRCA-positive tumors was the long arm of chromosome 6;
      alterations within this arm with a breakpoint in band 6q21 were seen in four of
      five BRCA1-positive and in two of three BRCA2-positive tumors, but only in four
      of 20 karyotypically abnormal tumors without BRCA mutations, suggesting that the
      genetic pathways of tumor progression differ in the two groups. The high
      frequency of germline BRCA mutations detected in this pilot study (16% of 37
      invasive carcinomas) points to the need for more extended analyses of population
      based series of patients to determine the true contribution of these predisposing
      genes to the overall incidence of ovarian cancer in this population.

PMID- 11240690
TI  - IgG antibodies against human papillomavirus type 16 E7 proteins in cervicovaginal
      washing fluid from patients with cervical neoplasia.
AB  - Little information is available about the cervicovaginal mucosal antibodies
      against human papillomavirus (HPV) proteins. In this study specific IgG
      antibodies against HPV 16 E7 protein were determined in paired samples of
      cervicovaginal washing fluid and serum from patients with cervical cancer (n =
      22), cervical intraepithelial neoplasia (CIN) (n = 38), healthy individuals (n =
      22), and serum from children (n = 41) by a radioactive immunoprecipitation assay
      (RIPA). HPV 16 E7 specific IgG antibodies were found in cervicovaginal washings
      (n = 8) and in sera (n = 8) of the patients with cervical cancer. About 60% of
      the patients with HPV 16 positive cervical cancer had HPV 16 E7 specific IgG
      antibodies. Titration studies showed that the IgG antibody reactivity in
      cervicovaginal washings was higher than in the paired serum samples of six
      patients with cervical cancer (P < 0.001). In the CIN group we found no IgG
      reactivity in the serum, but in five patients we found a low IgG reactivity in
      the cervicovaginal washings. No IgG reactivity was found in cervicovaginal
      washings and sera from healthy individuals and sera from children. HPV 16 E7
      specific IgG antibodies seem to be locally produced in a number of patients with
      HPV 16 positive (pre)malignant cervical lesions. For more definitive evidence for
      the local production of these antibodies immunostaining should be performed to
      demonstrate the presence of specific anti-HPV 16 E7 IgG producing plasma cells in
      the cervical epithelium.

PMID- 11240691
TI  - Overall 5-year survival rate and prognostic factors in patients with stage IB and
      IIA cervical cancer treated by radical hysterectomy and pelvic lymph node
      dissection.
AB  - The objective of this paper was to analyze the 5-year survival rate and
      prognostic factors for stage Ib and IIa cervical cancer treated by radical
      hysterectomy. A total of 366 patients with invasive cervical cancer treated by
      radical hysterectomy from June 1985 to June 1994 at Chonnam National University
      Hospital, Kwangju, Korea were retrospectively analyzed. Survival analysis was
      performed using the Kaplan-Meier estimator. Multivariate analysis was performed
      using the Cox proportional hazards regression model. The overall 5-year survival
      rate was 92% in stage Ib and 87% in stage IIa. Factors assessed for prognostic
      value included age, FIGO stage, cell type, tumor size, depth of invasion,
      lymphovascular space invasion (LVSI), and pelvic lymph node metastases (LNM). In
      the multivariate analysis, age, cell type, and lymph node metastases were
      independent predictors of survival. Lower survival was associated with age
      greater than 50 years, adenocarcinoma, and presence of lymph node metastases. The
      higher survival rates in patients with single lymph node involvement or lymph
      node metastases below the level of the common iliac nodes (85 and 84.6%,
      respectively) versus multiple or extrapelvic lymph node metastases (50 and 20%,
      respectively) were statistically significant (P < 0.01). In conclusion, patients
      who had lymph node metastases, adenocarcinoma, and were older than 50 years had a
      poorer survival rate. Such patients require more intense postoperative treatment
      and closer surveillance. Low-risk patients with a single lymph node metastasis
      below the level of the common iliac nodes may benefit from thorough
      lymphadenectomy without adjuvant therapy to prevent unpleasant complications.

PMID- 11240692
TI  - Parametrial spread in patients with endometrial carcinoma undergoing radical
      hysterectomy.
AB  - The objective of this paper is to study parametrial involvement in patients with
      endometrial carcinoma undergoing radical hysterectomy. We reviewed indications
      for surgery, pathology findings, and outcome of a series of 24 patients with
      endometrial carcinoma who underwent radical hysterectomy. The uterus, cervix and
      parametrial tissue were processed as step-serial sections. Histologically, 16
      patients (67%) had carcinoma involving the cervix. Two of these patients (8%) had
      frank histologic parametrial involvement and four (17%) had disease extending to
      the transitional zone of the cervix. Parametrial involvement was continuous and
      seen only in patients with involvement of the cervical stroma. Six patients (25%)
      had pelvic node metastases. With a median follow-up of 53 months (range 2-140),
      four patients (17%) developed recurrences (all within 24 months). Twelve patients
      (50%), including one of the two with parametrial invasion, were free of disease
      for 5 years or longer. We conclude that direct parametrial extension can occur in
      locally advanced endometrial cancer. Radical hysterectomy with lymphadenectomy
      can be an adequate operation for such patients.

PMID- 11240693
TI  - A retrospective comparison of current and proposed staging and scoring systems
      for persistent gestational trophoblastic disease.
AB  - It is widely accepted that patients with persistent gestational trophoblastic
      disease (GTD) are best managed by stratifying their treatment according to
      recognized adverse prognostic features. We retrospectively evaluated 201 patients
      who had received chemotherapy for persistent low or high risk GTD at the
      Sheffield Center according to criteria used in established and proposed WHO
      scoring and FIGO staging systems to identify the numbers of patients in each risk
      category, the treatment they would receive, chemotherapy resistance patterns, and
      eventual outcome. The systems were broadly comparable and chemotherapy resistance
      was always greater in the high-risk groups (at least 33%), particularly when
      patients were divided into just two risk categories. Such a categorization led to
      fewer patients (less than 15%) falling into high-risk groupings, but outcome was
      not compromised. Mortality (3 deaths) was associated with high risk
      categorization in all systems evaluated. A proposal to combine revised FIGO
      staging and modified WHO scoring systems, with two risk groupings, is realistic
      and practicable.

PMID- 11240694
TI  - Attitudes to radical gynecological oncology surgery in the elderly: a pilot
      study.
AB  - Does age-related inequality of cancer care reflect patient preference or
      physician prejudice? We hypothesize no difference between elderly and younger
      patients' desire for optimal surgery and disease cure, and psychological
      adaptation to cancer. A newly developed questionnaire to assess attitudes to
      radical gynecological surgery in the elderly (ARGOSE) and a battery of
      established instruments were administered to 54 gynecological cancer patients (32
      aged 65 + years; and 22 aged < 65 years) by structured interview. Disease
      diagnosis differed between cohorts (P = 0.007), but treatment modalities were
      similar (P = 0.46). There was no difference between cohorts in desire for optimal
      surgery and disease cure. Trends suggest the young consider a patient's age is
      less important than do the elderly, but the elderly may oppose age-related
      economic rationing of treatment more than the young. Furthermore, elderly
      individuals tend to perceive their seniors too elderly for treatment, but not
      themselves. The elderly believe more strongly that doctors should make management
      decisions. Perceptions of change in body image after cancer treatment did not
      differ between cohorts. The influence of age in determining attitudes is complex.
      A larger study with increased power is indicated to examine trends revealed in
      this pilot study.

PMID- 11240695
TI  - Nicked human chorionic gonadotropin in trophoblastic disease.
AB  - The objectives of this study were to determine: 1) whether high proportions of
      nicked human chorionic gonadotropin (hCG) in serum at the time of mole evacuation
      and during postmolar surveillance is indicative of trophoblastic malignancy and
      2) to investigate whether measurement of nicked hCG provides clinically more
      useful information in the management of patients with trophoblastic disease than
      does measurement of total hCG alone. "Tumor marker" total hCG, intact hCG, and
      nicked hCG were measured in serial samples of serum from our serum bank of
      patients with representative types of trophoblastic disease. "Tumor marker" hCG
      has been shown to measure all aspects of the hCG molecule. At the time of
      presentation of all 45 patients, 83.5% of hCG was intact and 16.5% was nicked.
      These proportions became reversed as hCG declined either spontaneously after
      hydatidiform mole evacuation or with chemotherapy in patients with postmolar
      trophoblastic tumor or with metastatic trophoblastic disease. We conclude that
      the proportion of nicked hCG compared to intact hCG increases with trophoblastic
      disease resolution. Measurement of nicked hCG adds no useful clinical information
      to that provided by reliable measurement of total hCG.

PMID- 11240696
TI  - Papillary serous adenocarcinoma of the endocervix: A rare neoplasm.
      Immunohistochemical profile.
AB  - Serous adenocarcinoma of the endocervix is a rare carcinoma similar to the serous
      carcinoma of the ovary and the endometrium. We report a case of a 63-year-old
      woman with papillary serous adenocarcinoma arising within the endocervix,
      describing the clinical presentation and the morphologic characteristics of this
      rare neoplasm. A detailed immunohistochemical analysis on the expression of low-
      and high-molecular weight cytokeratins (AE1 and AE3), EMA, CEA, vimentin, B72.3,
      nm23, estrogen and progesterone receptors, LeuM1 (CD15), p53, Ki-67 antigen, and
      PCNA by tumor cells has also been carried out, which to our knowledge has not
      been previously reported.

PMID- 11240698
TI  - Angiogenesis in the uterine cervix.
AB  - Our objective was to present current data pertaining to angiogenesis of the
      uterine cervix. We conducted a computerized search to identify relevant studies
      published in the English language literature. MEDLINE, Current Contents and Index
      Medicus were searched utilizing the terms: angiogenesis, uterine cervix,
      intraepithelial neoplasia, squamous cell carcinoma, and adenocarcinoma, from 1966
      through June 1999. In contrast to the cyclic phases of the menstrual cycle of the
      ovary and endometrium in which angiogenesis plays a significant physiologic role,
      angiogenesis in the uterine cervix is involved primarily in neoplastic processes.
      These include intraepithelial disease, human papilloma-related disease, and
      microinvasive and invasive squamous cell and adenocarcinoma of the cervix. In
      invasive squamous cell and adenocarcinoma of the uterine cervix, angiogenesis
      appears to be a prognostic indicator for overall survival and disease-free
      survival. Initial trial studies with anti-angiogenic (angio-inhibitor) therapy
      such as TNP-470 have been reported and concurrent antitumor activity observed in
      a limited number of patients with advanced (inoperable or metastatic) disease.

PMID- 11240697
TI  - Primary leiomyosarcoma of the vagina. A case report and literature review.
AB  - Primary vaginal leiomyosarcoma is a rare tumor. We report a unique case of a 27
      year-old woman with stage I, high-grade primary leiomyosarcoma of the vagina
      treated with surgical resection and adjuvant radiation therapy. She returned
      within 6 months with an abdominal-pelvic recurrence and lung metastases. The
      patient died of disease 9 months after diagnosis. A comprehensive review of
      primary vaginal leiomyosarcoma was performed and factors affecting survival were
      analyzed. A Medline search of the English-language literature revealed 66
      previously reported cases. Forty-eight of these had follow-up data. Survival
      probabilities were calculated using the Kaplan-Meier method, and the effects of
      age, stage, grade, tumor location, and treatment modality were analyzed. Stage
      III and IV data were combined. The overall 5-year survival rate was 43%. Patients
      more than 50 years of age had a 5-year survival rate of 26% compared with 51% for
      those less than 40 years. Five-year survival for stage I and II tumors was 55%
      and 44%, respectively. Patients with stage III/IV disease had 25% survival at 18
      months. No patient treated primarily with chemotherapy or radiation therapy
      survived beyond 36 months. In contrast, patients treated primarily with surgery
      had a 5-year survival rate of 57%. Only stage remained an independent predictor
      of survival on Cox regression analysis. We continue to recommend surgical
      resection as primary treatment. Exenteration may be an option for select
      patients, but ultimately management should continue on a case-by-case basis.

PMID- 11240699
TI  - Phase II study of vincristine, bleomycin, mitomycin C and cisplatin (VBMP) in
      disseminated squamous cell carcinoma of the uterine cervix.
AB  - The objective of this study was to study the antitumor activity of the
      vincristine, bleomycin, mitomycin C and cisplatin (VBMP) scheme in patients with
      disseminated squamous cell carcinoma of the uterine cervix and to document its
      toxicity. VBMP consisted of vincristine 1.4 mg/m2 (max. 2 mg) i.v. day 1,
      bleomycin 15 mg/day by continuous i.v. infusion on day 1 + 2, mitomycin C 6 mg/m2
      i.v. day 3 and cisplatin 50 mg/m2 i.v. day 4, and was given every 4 weeks.
      Bleomycin was withdrawn from the schedule after a cumulative dose of 300 mg (210
      mg in patients over 60). Thereafter VMP continued (V + M day 1, P day 2) with the
      same interval. A median number of 4.5 (range 2-13) treatment cycles was given to
      50 fully evaluable patients, 26 with only distant metastases (group A) and 24
      with pelvic disease also (23 previously irradiated) (group B). All patients were
      < 70 years old, had a Karnofsky index >/=60, and measurable metastatic lesions
      outside previously irradiated areas. They all had normal organ functions and gave
      informed consent. Response in group A was 54% (31% complete), in group B 25% (all
      partial), 40% in all. Median time to progression in group A was 20 weeks and in
      group B 15 weeks; median survival was 42 weeks in group A, 32 weeks in group B,
      37 weeks for all patients. Hematologic toxicity was cumulative and the majority
      of patients needed blood transfusions. Nonhematologic toxicity was acceptable,
      but in one patient pulmonary toxicity might have contributed to death. Although
      it is active, it is unclear whether this regimen is superior to cisplatin alone.

PMID- 11240700
TI  - Brain metastases from epithelial ovarian carcinoma.
AB  - BACKGROUND: Brain metastases from epithelial ovarian carcinoma are rare. We
      reviewed our experience to evaluate the results of different treatments and their
      prognosis. Discussion is based on a review of the literature. METHODS: From 1974
      to 1998, eight of 704 patients treated for epithelial ovarian carcinoma at our
      large cancer center developed brain metastases. The median time before occurrence
      of brain metastases was 15 months after the diagnosis of the ovarian cancer. Six
      patients had a single lesion and two had multiple parenchymal lesions. Brain was
      the only site of disease in one patient, while seven had concomitant
      dissemination. Seven out of eight patients underwent a treatment for brain
      metastases. The treatment consisted of either radiotherapy (2 cases),
      chemotherapy (2 cases), surgery and radiotherapy (1 case), or combined treatment
      of the three modalities (2 cases). RESULTS: Median survival from diagnosis of
      brain lesions was 3 months (range 1-12). One patient without treatment died one
      month later. Survival after complete surgical resection and radiotherapy was 12
      months. One patient treated by complete surgical resection followed by
      radiotherapy and chemotherapy is still alive (+ 5 months). The patient who
      underwent partial surgical resection followed by radiotherapy and chemotherapy
      died 7 months later. Two patients treated by radiotherapy alone died,
      respectively, 2 and 3 months later. After systemic chemotherapy alone, survival
      times were 1 and 3 months. Conclusions. The prognosis of patients with brain
      metastases from ovarian carcinoma is poor. A better outcome might be obtained by
      a multimodal treatment.

PMID- 11240701
TI  - Clinical relevance of urokinase-type plasminogen activator, its receptor and
      inhibitor type 1 in ovarian cancer.
AB  - Urokinase-type plasminogen activator (uPA), its receptor (uPAR) and inhibitor,
      plasminogen activator-type 1 (PAI-1) are proposed to be of prognostic
      significance in some cancers. To determine the prognostic value of the urokinase
      plasminogen activation system in ovarian cancer, levels of uPA, uPAR, and PAI-1
      were measured in extracts of ovarian cancer tissue using ELISA tests. uPA and PAI
      1 were determined in 70 tumor extracts and uPAR in 43 extracts. Levels were
      correlated with age, tumor histology, stage, grade, lymph node and metastatic
      status, residual disease, risk of recurrence, epidermal growth factor receptor
      (EGFR) expression, cathepsin D (Cath-D), and c-erbB-2 levels. uPA and uPAR did
      not exhibit correlation with any of these parameters. However, patients with high
      grade tumor, recurrence, and lower EGFR and Cath-D had significantly higher PAI-1
      levels compared to those of others (P < 0.05). Kaplan-Meier plots of survival
      were compared. uPA and uPAR were not related to disease-free or overall survival.
      Although low PAI-1 appeared to predict a longer overall survival, the difference
      was not statistically significant. Multivariate analysis revealed that PAI-1 was
      a predictor for overall survival although it was not as strong as stage. These
      results suggest that elevated PAI-1 seems to be correlated with an unfavorable
      prognosis in ovarian cancer.

PMID- 11240702
TI  - Management of vaginal intraepithelial neoplasia: A series of 132 cases with long
      term follow-up.
AB  - A series of 132 cases of vaginal intraepithelial neoplasia (VAIN) is presented,
      including nine (6.8%) where early invasive carcinoma of the vagina was found in
      the course of initial management of the VAIN. The majority of patients (75%) had
      high-grade VAIN (two or three). Seventy-two (55%) had undergone a prior
      hysterectomy; 22 for preinvasive disease (CIN), 33 for invasive gynecological
      cancer, 13 for benign reasons, and in 4 the reason for the hysterectomy and/or
      the Pap smear history was not known. Twenty-one (16%) had received prior pelvic
      radiotherapy. VAIN was noted to involve either the vaginal vault (in the post
      hysterectomy group) or the upper vagina (in the no hysterectomy group) in more
      than 80% cases. A variety of treatment modalities was used with varying degrees
      of success. For high-grade VAIN excisional treatments had an overall (first-line
      plus subsequent) cure rate of 69% (53/77). The state of the surgical margins did
      not correlate with the risk of residual disease. CO2 laser ablation was curative
      in 69% (18/26) of cases and was significantly better than electrocoagulation
      diathermy which was curative in only 25% (3/12) of cases (P = 0.013). Five
      fluorouracil cream was curative in 46% (5/11) of cases, including four patients
      who had received prior radiotherapy. Radiotherapy was effective in eradicating
      VAIN in the two cases where it was used as the primary treatment modality.
      Progression of high-grade VAIN to invasive cancer occurred in eight (8%) cases;
      after no treatment in two cases, after treatment failure in five cases, and as a
      late recurrence in one case. For low-grade VAIN an observational approach after
      biopsy was initially adopted in eight patients and regression occurred in seven
      (88%) of these patients. Other miscellaneous treatments were also effective in
      low-grade VAIN. These data provide evidence that high-grade VAIN is a precursor
      to invasive cancer of the vagina and every attempt should be made to eradicate
      it. Based on our experience and a review of the literature we have proposed a
      plan for optimal management of this condition.

PMID- 11240703
TI  - Cancer of the vagina: Laminin-5gamma2 chain expression and prognosis.
AB  - The purpose of this experiment was to investigate the expression and the
      prognostic impact of the gamma2 subchain of laminin-5 in vaginal malignancies.
      The outcome of the rare disease primary carcinoma of the vagina is poor and
      little is known about prognostic markers. The gamma2 chain of laminin-5, an
      epithelial basement membrane protein, is thought to play a crucial role in tumor
      cell adhesion, migration, and proliferation, and may thus be an additive
      potential marker. Archival, paraffin-embedded sections were stained
      immunohistochemically with an antibody against the gamma2 chain of human laminin
      5 protein. The material consisted of 59 cases of primary vaginal malignancies,
      subdivided into short- and long-time survivors. All invasive malignancies of
      epithelial origin were positively stained with the antibody against the gamma2
      chain. High expression of the gamma2 chain correlated significantly in an
      univariate analysis with short-time survival (P = 0.041), but in the multivariate
      analysis only age and tumor size were independent prognostic factors. A
      significant intercorrelation between large tumors and high gamma2 chain
      immunoreactivity was found (P = 0.003). These results indicate that laminin
      5gamma2 subchain expression in primary vaginal carcinomas is of prognostic
      impact. However, in a multivariate analysis only patient age and tumor size had
      independent prognostic value.

PMID- 11240704
TI  - The significance of tumor size in clinical stage IB cervical cancer: Can a cut
      off figure be determined?
AB  - The purpose of this study was to investigate the influence of tumor size on
      pathologic variables and the prognosis of patients diagnosed as clinical stage IB
      cervical cancer. Five hundred sixty six patients with clinical stage IB cervical
      cancer treated surgically at the Aichi Cancer Center between 1976 and 1995 were
      studied. The incidence of pathologic variables that increased as tumors enlarged
      was unchanged beyond 4.0 cm. Although univariate analysis revealed that the
      prognosis worsened as a tumor enlarged, there was no significant difference in
      prognoses between 3.1-4.0 cm and 4.1-5.0 cm tumors. While multivariate analysis
      showed tumor size as an independent prognostic variable, there was no difference
      between the odd ratios of 3.1-4.0 cm and 4.1-5.0 cm tumors. Tumor size was an
      independently significant risk factor for the prognosis of clinical stage IB
      cervical cancer. While the definition of 4.0 cm as a cut-off point was useful as
      far as determining an association with pathologic variables, it may be an
      insufficient indicator of poor prognosis. The "bulky" tumors should be defined as
      clinical lesions greater than 5.0 cm, though few patients would have tumors that
      meet that criterion.

PMID- 11240706
TI  - Cervical carcinoma with rhabdoid phenotype: Report of two cases.
AB  - This report documents two cases of cervical carcinomas having a prominent
      rhabdoid cell component. In one instance, rhabdoid cells were present as a
      component of endocervical adenocarcinoma, whereas in the other case, an
      undifferentiated cervical carcinoma developed a prominent rhabdoid phenotype on
      recurrence. Like tumors containing rhabdoid elements which have been described at
      other sites, these neoplasms behaved in an aggressive manner.

PMID- 11240705
TI  - p53 Polymorphism (codon-72) has no correlation with the development and the
      clinical features of cervical cancer.
AB  - Recent analysis of the codon-72 polymorphism of the p53 gene, the allele encoding
      proline or arginine, suggested that the homozygous Arg/Arg genotype is a
      significant risk factor for cervical cancer associated with human papillomavirus
      (HPV). We investigated the polymorphism of p53 in cervical condylomas, cervical
      intraepithelial neoplasias (CINs), and cervical cancers, evaluating clinical
      implications of the polymorphism of p53 in development of cervical neoplasms. DNA
      from 87 cervical cancer tissues, 28 CIN tissues, and seven cervical condyloma
      tissues were examined for the presence of HPV DNA by the consensus PCR method and
      the p53 polymorphism was analyzed by PCR using an allele-specific primer. The
      frequencies of p53Pro, p53Arg, and p53 Pro/Arg were 14.3%, 57.1%, and 28.6% in
      condyloma patients; 21.4%, 39.3%, and 35.7% in CIN patients; and 10.3%, 44.8%,
      and 42.5% in cervical cancer patients, respectively. No statistically significant
      differences in the distribution of p53 genotypes were found among the patients
      with these diseases, regardless of HPV status. Furthermore, there was no clear
      correlation between the polymorphism of p53 and age, histopathologic type,
      clinical stage, or lymph node metastasis. Nor was there any evidence of a
      correlation between the p53 genotype and the outcome for patients with HPV
      positive uterine cervical cancer.

PMID- 11240707
TI  - Site specific lymph node metastasis in carcinoma of the cervix: Is there a
      sentinel node?
AB  - Follow-up for at least 5 years was available for 350 cases of stage IB and IIA
      carcinoma of the cervix managed by radical hysterectomy and pelvic
      lymphadenectomy. Lymphadenectomy technique mapped the patterns of pelvic lymph
      node metastasis (LNM). The effects on survival of specific factors relating to
      the lymphadenectomy (node count, number of positive nodes, site of positive
      nodes, number of sites positive, location of highest positive node) were
      determined for 80 women with LNM. The location of metastatic disease did not
      significantly predict survival. The incidence of LNM was 23% and 47.5% of these
      women survived 5 years. Only 45% of cases with a solitary LNM survived 5 years
      and in 45% of these recurrence was outside the pelvis. With the exception of the
      presacral group, the finding of isolated LNM in any other group with metastasis
      to the left side of the pelvis conferred the worst prognosis. The pattern of LNM
      from early stage carcinoma of the cervix is therefore random and the concept of a
      sentinel node or group is not tenable.

PMID- 11240708
TI  - Expression of TRAIL (TNF-related apoptosis-inducing ligand) receptors in cervical
      cancer.
AB  - Apoptosis is an intrinsic and fundamental biologic process that plays a critical
      role in the normal development of multicellular organisms and in the maintainance
      of tissue homeostasis. Some of the well known regulators of apoptosis are
      cytokines of the tumor necrosis factor (TNF) ligand family, such as Fas ligand
      (Fas L) and TNF, which induce apoptosis by activation of their corresponding
      receptors, Fas and TNFR-1. Recently, a new member of the TNF family known as
      TRAIL (TNF-related apoptosis-inducing ligand) was identified and shown to induce
      p53-independent apoptosis in a variety of tumor cell lines but not in normal
      cells. Four human receptors for TRAIL were also recently identified and
      designated TRAIL-R1, -R2, -R3, and -R4. The aim of this study is to examine
      whether TRAIL and TRAIL receptors (-R1, -R2, -R3) are expressed in uterine
      cervical cancer and whether it is correlated with apoptosis, TRAIL, and TRAIL
      receptors. The subjects were 20 patients who were diagnosed with cervical cancer.
      Western blotting was performed in nine cases and immunohistochemical staining for
      TRAIL and TRAIL receptors (-R1, -R2, -R3) and TUNEL method for detection of
      apoptosis was performed in 11 cases. There were proteins for TRAIL, TRAIL-R1, 
      R2, and -R3 in tissues from cervical cancer. All TRAIL receptors were expressed
      in both normal cervical epithelium and tumor cells, and TRAIL-R1 and -R2 were
      more strongly expressed in tumor cells than normal epithelium (P < 0.05).
      Apoptosis correlated with expression of TRAIL-R1 and -R2 (P < 0.05). This study
      suggests that TRAIL induces apoptosis in cervical cancer through its receptors.

PMID- 11240709
TI  - Combined diagnostic imaging of uterine carcinosarcoma: A case report.
AB  - The diagnostic imaging characteristics of uterine carcinosarcoma have not been
      established because the tumor is very rare. We studied magnetic resonance (MR)
      imaging, power Doppler ultrasonography, and positron emission tomography (PET) in
      one such carcinosarcoma to define its imaging characteristics. On T1-weighted MR
      images, the tumor mass in the uterus was low-signal intensity and had a slight
      inhomogeneous appearance. On T2-weighted images, it had a heterogeneous
      appearance and was of medium- or high-signal intensity; marked flow void was
      apparent from the myometrium to the tumor mass. The MR flow void was also
      detected by power Doppler ultrasonography. Increased glucose metabolism was
      detected on PET images, suggesting a malignant tumor in the endometrial cavity.
      Combined diagnostic images with MR, power Doppler ultrasonography, and PET is
      recommended as the diagnostic method for uterine carcinosarcoma.

PMID- 11240710
TI  - Malignant granular cell tumor of the vulva in a 17-year-old: Case report and
      literature review.
AB  - Granular cell tumors are uncommon soft tissue tumors. Although the majority of
      these tumors are benign, a rare malignant variant exists which is aggressive,
      with local recurrence rates up to 70% and 3-year survival rates of less than 50%.
      We present a case of malignant granular cell tumor of the vulva in a 17-year-old,
      the sixth such case to be reported at this site. She was treated with a left
      hemivulvectomy and ipsilateral groin node dissection followed by postoperative
      radiation therapy. She remains free of disease at 16 months. Patients with
      malignant granular cell tumor or granular cell tumor of malignant potential are
      best managed with wide local excision and regional lymph node dissection.

PMID- 11240711
TI  - Value of lymph node assessment in ovarian cancer: Status of the art at the end of
      the second millennium.
AB  - Available data on the incidence and the clinical value of lymph node assessment
      in ovarian cancer are reported. In early ovarian cancer, positive nodes are found
      in 4-25% of patients. Serous adenocarcinoma and poorly differentiated tumors are
      characterized by the highest incidence of node metastases. Five-year survival for
      stage IIIC disease with only retroperitoneal spread is clearly better than for
      stage IIIC with intraperitoneal dissemination. In advanced ovarian cancer, the
      rate of node involvement ranges from 55 to 75%. The percentage of positive nodes
      is significantly related to the amount of residual tumor after cytoreductive
      surgery, and node status seems to be an important prognostic factor for survival.
      Although data from retrospective studies advocate a therapeutic effect for
      systematic lymphadenectomy, results from prospective randomized trials are
      warranted. After chemotherapy a high percentage of patients (range, 25-77%) are
      found to have metastatic nodes. In particular, at second-look laparotomy,
      positive nodes are detected in 17-40% of patients who have no intraperitoneal
      disease.

PMID- 11240712
TI  - An open label evaluation of topotecan in patients with relapsed or refractory
      epithelial ovarian cancer - single institution experience in a developing
      country.
AB  - Investigators in developing countries rarely get an opportunity to participate in
      clinical drug trials in oncology. We recently participated in two clinical trials
      involving the use of topotecan in patients with advanced epithelial ovarian
      cancer who had failed initial platinum based chemotherapy. It provided us an
      opportunity to gain experience with the use of a rather highly myelosuppressive
      drug and also enabled us to compare our data with those reported from the western
      countries. Thirty-nine patients with good performance status and adequate bone
      marrow, liver, and renal functions were accrued. All patients had previously
      received at least one platin containing regimen of chemotherapy. The most common
      histologic sub type was serous adenocarcinoma. Almost half of the patients had
      platinum refractory disease. Mean number of cycles delivered was 7.5. Eleven
      patients (28%) achieved complete or partial remission. Time to progression was
      4.6 months. Mean overall survival was 11.3 months. Toxicity was primarily
      hematologic and manageable. Performance status was the only variable predictive
      of response. Ability to obtain informed consent, data management, and
      availability of adequate radiologic and laboratory facilities were important
      limitations. Our results confirm the applicability of results obtained in the
      western countries to other patient groups and ability to conduct clinical trials
      in oncology in the developing countries.

PMID- 11240713
TI  - An analysis of ovarian tumor diameter and survival.
AB  - Residual disease following primary debulking surgery is a recognized prognostic
      factor in ovarian cancer. Few studies have looked at the effect of initial
      ovarian tumor diameter on survival. As larger tumors are more likely to be
      detected by ultrasound, this information may be important in determining a
      survival benefit in screen-detected cancers. We reviewed the case notes and
      pathology of 168 consecutive cases of primary debulking surgery in epithelial
      ovarian cancer. We examined the influence of ovarian tumor diameter on survival
      and its relationship to CA125 levels and stage. For the purposes of analyses, we
      divided subjects into two groups: those with tumors < 6 cm and those with tumors
      > 6 cm. There were significant differences between the groups, with smaller
      tumors having more advanced stage disease compared to larger tumors (chi23 =
      15.7, P = 0.0013) The median survival for tumors less than or equal to 6 cm was
      17months (95% confidence interval [95% CI], 12 to 22), while for tumors greater
      than 6cm, the median survival was 36 months (95% CI, 13 to 59; logrank test =
      8.61, P = 0.003). However, stage is also an important predictor of survival, and
      in a multivariate analysis, tumor size was not found to be an independent
      prognostic factor. There was no significant difference between the groups for
      CA125 levels. As larger diameter ovaries are more likely to be detected by
      ultrasound, it may be that screen-detected ovarian cancers will show a survival
      benefit simply because they detect a subset of ovarian cancers that are
      associated with a better prognosis.

PMID- 11240714
TI  - Loss of heterozygosity among tumor suppressor genes in invasive and in situ
      carcinoma of the uterine cervix.
AB  - The aim of the present study was to further clarify the histogenesis of cervical
      carcinoma by investigating loss of heterozygosity (LOH) among a number of tumor
      suppressor genes in invasive and in situ carcinoma of the cervix. Materials
      consisted of 16 in situ and 29 invasive carcinomas (16 squamous cell carcinomas,
      nine adenocarcinomas, and four adenosquamous carcinomas). DNA samples were
      collected by microdissection from ordinary formalin-fixed, paraffin-embedded
      tissues, both from the lesions and from normal tissues. LOH was analyzed using
      eight DNA polymorphic tumor suppressor markers. Of the 16 cases of carcinoma in
      situ, three cases exhibited LOH at one locus. Of the 29 cases of invasive
      carcinomas, six cases exhibited LOH at two loci and nine cases exhibited LOH at
      one locus. Overall, LOH was found more frequently in invasive carcinomas than in
      in situ carcinomas. LOH was most frequently detected at the PTCH (Drosophila
      patched gene) locus. There was no significant correlation between LOH at a
      specific site and either histologic subtype or clinical stage. These results
      suggest that LOH might already occur in a fraction of preinvasive squamous
      lesions and that accumulation of LOH may in part play a role in carcinogenesis of
      the cervix.

PMID- 11240715
TI  - Paclitaxel in combination with cisplatin is less effective for peripheral blood
      progenitor cell mobilization.
AB  - The purpose of this study was to determine the efficacy of paclitaxel in
      combination with cisplatin and granulocyte-colony stimulating factor (G-CSF) for
      mobilization of peripheral blood progenitor cells (PBPC). Twenty-seven patients
      with gynecological cancer received paclitaxel and cisplatin (TP, n = 9) or other
      platinum-based chemotherapy (n = 18) (etoposide and cisplatin [n = 5];
      cyclophosphamide, adriamycin, and cisplatin [n = 8]; or pepleomycin, etoposide,
      and cysplatin [n = 5]). Each combination was followed by G-CSF. The mean number
      of colony-forming unit granulocyte macrophage (CFU-GM)/kg and CD34+ cells/kg
      collected per cycle was 1.2 x 105 and 0.8 x 106 after the TP regimen, compared
      with 2.6 x 105 (P < 0.05) and 2.0 x 106 for patients who received other platinum
      based chemotherapy. The CFU-GM target yield (>/=1.0 x 105/kg) was achieved in 56%
      and 83% patients in the TP and comparison group, respectively. With the TP
      regimen, a younger age (</=50 years of age) and fewer prior chemotherapy cycles
      (</=2) were associated with the CFU-GM targeted yield (<0.05). In conclusion, TP
      mobilized PBPC less effectively than other platinum-based chemotherapy.
      Therefore, the TP regimen may need to be changed to another appropriate regimen
      when PBPC mobilization is planned for high-dose chemotherapy in gynecological
      cancer patients.

PMID- 11240716
TI  - Treatment of advanced ovarian carcinoma with carboplatin and paclitaxel in a
      patient with renal failure.
AB  - Platinum-based chemotherapy is the standard treatment for ovarian cancer. Since
      carboplatin elimination occurs largely through the kidneys, its use in patients
      with hemodialysis-dependent renal failure requires dose adjustments befitting the
      level of renal function. We employed the AUC (area under the concentration-time
      curve)- directed dosing strategy (the Calvert formula) to determine the
      carboplatin dose appropriate for an ovarian cancer patient with renal failure.
      Our approach is compared and defended against the empiric and thrombocyte nadir
      directed dosing strategies. Since carboplatin clearance follows creatinine
      clearance, we also provide a review of methods and formulas used to determine
      creatinine clearance. An accurate method to determine creatinine clearance will
      enable others to use the AUC-directed dosing strategy to establish the
      carboplatin dose appropriate for patients with some residual renal function.

PMID- 11240717
TI  - Comparison of macroscopic appearance and estrogen receptor-alpha regulators after
      gene alteration in human endometrial cancer.
AB  - The existence of two types of endometrial cancer (hyperplasia-associated type
      [type I] and atrophy-associated type [type II]) is well established. To test if
      different molecular genetic pathways are involved in the pathogenesis of type I
      and II disease, we examined pathologic features and the genetic alterations of K
      Ras, MDM2 and p53 (which are considered to be involved in regulation of the
      estrogen receptor-alpha) in human endometrial tissue samples using several
      modified PCR methods. We found a significant difference in histologic grade (P <
      0.001), degree of invasion (P < 0.001), stage grouping (P < 0.001) and estrogen
      receptor status (P < 0.01) between type I and II cases. There was a tendency for
      cases with K-Ras point mutations to be of type I, and for cases with the p53
      point mutation to be of type II; however, we found that these mutations or
      alternative splicing of MDM2 was rarely involved and there was no significant
      difference in frequency of these alterations between types I and II. There must
      therefore be another structural or functional difference of Ras, MDM2 or p53
      between type I and type II cancer. These unknown factors may be responsible for
      the difference between estrogen-dependent and estrogen-independent growth in
      human endometrial cancer.

PMID- 11240718
TI  - Prognostic significance of cell cycle proteins and genomic instability in
      borderline, early and advanced stage ovarian carcinomas.
AB  - Disturbed cell cycle-regulating checkpoints and impairment of genomic stability
      are key events during the genesis and progression of malignant tumors. We
      analyzed 80 epithelial ovarian tumors of benign (n = 10) and borderline type (n =
      18) in addition to carcinomas of early (n = 26) and advanced (n = 26) stages for
      the expression of Ki67, cyclin A and cyclin E, p21WAF-1, p27KIP-1 and p53 and
      correlated the results with the clinical course. Genomic instability was assessed
      by DNA ploidy measurements and, in 35 cases, by comparative genomic
      hybridization. Overexpression of cyclin A and cyclin E was observed in the
      majority of invasive carcinomas, only rarely in borderline tumors and in none of
      the benign tumors. Similarly, high expression of p53 together with undetectable
      p21 or loss of chromosome arm 17p were frequent events only in adenocarcinomas.
      Both borderline tumors and adenocarcinomas revealed a high number of chromosomal
      gains and losses. However, regional chromosomal amplifications were found to
      occur 13 times more frequently in the adenocarcinomas than in the borderline
      tumors. The expression pattern of low p27 together with high Ki67 was found to be
      an independent predictor of poor outcome in invasive carcinomas. The results
      provide a link between disturbed cell cycle regulatory proteins, chromosomal
      aberrations and survival in ovarian carcinomas.

PMID- 11240719
TI  - Experience of the Gynecologic Oncology Unit at Ain Shams University in the
      treatment of gestational trophoblastic tumors.
AB  - The aim of the study is to evaluate the different treatment modalities in the
      management of gestational trophoblastic tumors (GTT) in a tertiary care setting.
      One hundred and twenty patients between 16 and 55 years of age (mean 30.6)
      diagnosed and treated for GTT at the Gynecologic Oncologic Unit, Ain Shams
      University, between June 1992 and November 1998 were studied. The mean parity of
      the group was 2.5 (0-12) with a mean follow-up of 47.4 months (16-96). One
      hundred cases (83.3%) followed a molar pregnancy, while 17 (14.2%) and three
      (2.5%) had an antecedent abortion and term pregnancy, respectively. By adopting
      the National Institutes of Health Classification due to its practicality, 65
      (54.1%) were nonmetastatic and 55 (45.9%) were metastatic; 17 (14.2%) low-risk
      metastatic and 38 (31.7%) high-risk metastatic. Forty-two patients (35%) had a
      hysterectomy, which was curative in 16 (13.3%). In the high-risk metastatic
      group, 22 patients were treated with EMA achieving a complete stable remission in
      19 (86.3%) with one of the remaining three being salvaged by EMA-EP. One hundred
      fourteen (95%) patients are alive and well without evidence of disease with all
      six deaths occurring in the high-risk metastatic group. One of the deaths was due
      to unrelated disease (repeat variceal hemorrhage from portal hypertension), while
      the remaining five followed nonmolar pregnancies with four having brain and/or
      liver metastases and another presenting with resistant fatal acute respiratory
      distress syndrome (ARDS) despite optimal support. By using multivariate analysis,
      it was found that only the presence of brain and/or liver metastases, followed by
      an antecedent nonmolar pregnancy and resistance to multiple agent chemotherapy
      were significant as regards the prognosis of high-risk metastatic GTT. These
      tumors are highly curable with death almost limited to those with brain and/or
      liver metastases, particularly following nonmolar pregnancies. In these extremely
      high-risk categories, elaboration of more intensive and innovative combination
      chemotherapy protocols is needed in order to achieve better results than those
      currently reported. In addition the use of EMA instead of EMA-CO deserves to be
      tested in properly randomized controlled collaborative studies to reduce
      treatment toxicity.

PMID- 11240720
TI  - Histologic study of patterns of cervical involvement in FIGO stage II endometrial
      carcinoma.
AB  - The pathology of cervical involvement in endometrial carcinoma has not been fully
      defined previously. We reviewed the histopathology of 66 hysterectomies of women
      with stage II endometrial carcinoma. Cervical spread was categorized as
      macroscopic or microscopic; stage IIA or IIB; direct spread, surface or
      lymphvascular metastasis; and size, number, and location. The cervical tumor was
      macroscopically identified in 15 (23%) women and microscopically identified in 51
      (77%). Twenty-one patients (32%) were stage IIA and 45 (68%) stage IIB. The
      method of spread was direct spread in 28 patients, surface metastases in 27,
      lymphovascular in 3, both direct spread and surface metastases in 7 and both
      direct spread and lymphovascular in 1. The cervical tumor had a mean horizontal
      dimension of 3 mm and a median of 2 mm. There were multiple sites of cervical
      tumor in 31 (47%) patients and single in 35 (53%). The sites of spread, including
      cases with multiple sites, were the endocervix in 60 women (90%), transformation
      zone in 24 (37%), and ectocervix in 3 (5%). Most patients had minimal microscopic
      cervical tumor. Small examples of direct spread may be an artifact of definition
      depending on the histology of the isthmian-endocervical junction and many surface
      metastases appear to follow dilatation and curettage. In 7 of 66, 11%, however,
      the cervical tumor was greater than 5 mm depth of invasion and/or the result of
      lymphvascular metastasis. Survival studies are required to compare minimal stage
      II endometrial carcinoma patients and those with larger and/or lymphvascular
      derived cervical tumor. Patients with minimal stage II and stage I patients
      should also be compared.

PMID- 11240721
TI  - A benign-looking subcutaneous metastasis from squamous cell cervical carcinoma: A
      case report and review of the literature.
AB  - A 30-year-old woman with a stage IIIB grade 3 squamous cell cervical carcinoma
      and pelvic lymph node metastases was treated with external beam radiotherapy and
      intracavitary brachytherapy. One month after the completion of the treatment, a
      rubbery, movable, and painless mass appeared in the lower third and outer aspect
      of her right thigh. The overlying epidermis was intact. The whole clinical
      picture and CT scan image indicated a benign tumor. Biopsy revealed a
      nonkeratinizing, grade 2-3, squamous cell carcinoma similar to the primary
      cervical tumor. She then received six cycles of chemotherapy (cis-platinum and 5
      fluorouracil) with transient partial response. The patient died one year after
      the diagnosis of the disease. This is the 29th case of cutaneous metastasis from
      a cervical carcinoma, the seventh localized on the leg, but the first solitary
      one with a benign-looking appearance reported since 1855. The possible mechanism
      of this rare metastasis is debated and the literature is reviewed.

PMID- 11240722
TI  - Palmar fasciitis and polyarthritis associated with squamous cell carcinoma of the
      cervix.
AB  - Palmar fasciitis and polyarthritis (PFPA) is an uncommon syndrome characterized
      by progressive and extensive rheumatic disease. We present the first example of
      PFPA in association with squamous cell carcinoma of the uterine cervix and
      peritoneal carcinoma. A 54-year-old woman developed pain in both shoulders and
      flexion deformities of all fingers in both hands due to an increasing swelling of
      both palms. She underwent surgery and histologic examination of the removed
      uterus revealed squamous cell carcinoma, nonkeratinizing type with a small
      portion of undifferentiated carcinoma. Chemotherapy resulted in an excellent
      response, during which the arthritic symptoms improved gradually. PFPA can occur
      in a wide range of cancers and warrants extensive investigation for a malignant
      tumor.

PMID- 11240723
TI  - Preface.

PMID- 11240724
TI  - Molecular approaches to management of epithelial ovarian cancer.

PMID- 11240725
TI  - Staging of early ovarian cancer and the impact of lymph node sampling.

PMID- 11240726
TI  - Surgical versus chemical upfront debulking in advanced ovarian cancer.

PMID- 11240727
TI  - The impact of specialist training for surgery in ovarian cancer.

PMID- 11240728
TI  - Intravenous chemotherapy for ovarian cancer - the state of the art?
AB  - In 1999, two cytotoxic drug classes have emerged as essential components of
      intravenous chemotherapy for advanced ovarian cancer: the taxoids and the
      platinum compounds. Two large-scale randomized trials were required to convince
      most oncologists (and health care purchasers) that the combination of paclitaxel
      and cisplatin could be considered as standard therapy. Remarkably, the survival
      advantage achieved over treatment with cyclophosphamide and cisplatin
      (approximately 12 months) was virtually the same in the two trials (one in the
      USA, one an international Intergroup), despite differences in trial design. While
      these trials were proceeding, others continued to examine the role of
      carboplatin, and an overview by meta-analysis suggests this compound has equal
      efficacy as cisplatin at appropriate doses, but with much less toxicity. A
      paclitaxel-carboplatin regimen therefore has been widely adopted, particularly as
      this combination demonstrates the intriguing phenomenon of platelet-sparing,
      allowing full doses of both agents to be given. Preliminary results from three
      trials indicate equivalence between this combination and paclitaxel-cisplatin,
      with clear benefits in terms of toxicity, although mature survival data are not
      yet available. Many unanswered questions remain regarding intravenous
      chemotherapy. These include optimal duration (particularly for a taxoid) and the
      potential benefit for the addition of a third agent, either an established agent,
      such as an anthracycline or etoposide, or a newer agent, such as topotecan or
      gemcitabine. Three drug combinations may lead to innovative trial designs; a
      promising candidate might be sequential therapy. For the two lead drugs, other
      schedules, eg, a sequential approach, merit assessment, and alternative agents
      such as docetaxel and oxaliplatin also provide intriguing preclinical and early
      clinical data. Thus the stage is set for a number of interesting trials in the
      coming years.

PMID- 11240729
TI  - The role of intraperitoneal chemotherapy in epithelial ovarian cancer.
AB  - Intraperitoneal chemotherapy for the treatment of patients with epithelial
      ovarian cancer is theoretically an attractive approach taking into account the
      biology of the disease, the physiologic and anatomic characteristics of the
      peritoneal cavity, and the pharmacologic advantage of several anticancer agents
      when administered intraperitoneally compared to intravenously. In patients with
      advanced disease it can be used either as initial chemotherapy, for
      consolidation, or as salvage treatment. However, in all clinical settings only
      those with no gross residual disease or those with macroscopically very small
      volume residual disease (tumor nodules </=0.5-1 cm in maximum diameter) are
      suitable for this approach. Intraperitoneal chemotherapy is unlikely to be
      beneficial in more bulkier disease since drug penetration into larger tumor
      nodules is limited. Available trial data are summarized. Randomized trials in
      first-line suggest a superiority of intraperitoneal over intravenous
      chemotherapy, at least for cisplatin. However, further well designed randomized
      studies are necessary to assess and confirm whether intraperitoneal chemotherapy
      is superior over the new standard, ie, intravenous paclitaxel combined with
      intravenous cisplatin or carboplatin. Although the application of intraperitoneal
      chemotherapy as salvage treatment or for consolidation is theoretically
      attractive and some indirect indications of its effectiveness are present, in the
      absence of randomized studies its routine use cannot be recommended as yet and
      should be restricted to research settings.

PMID- 11240730
TI  - Optimum chemotherapy for ovarian cancer.
AB  - A series of prospective randomized trials recently have defined the new standard
      of care for chemotherapy patients with ovarian cancer. The current preferred
      regimen consists of carboplatin (dosed to an area-under-the-curve [AUC] of 5.0
      7.5) plus paclitaxel (175 mg/m2-3 h infusion). This is an outpatient regimen that
      does not require growth factor support and six cycles are administered on a 21
      day schedule. There is no evidence that any type of additional therapy impacts
      upon survival, including additional cycles of the same chemotherapy or switching
      to an alternative intravenous chemotherapy, high-dose chemotherapy with
      hematologic support, intraperitoneal chemotherapy, or whole abdominal radiation.
      The majority of patients will achieve a clinical complete remission with the
      regimen although the relapse rate remains high. Current trials are exploring new
      schedules of drug delivery as well as new combinations which include new agents
      such as gemcitabine and topotecan.

PMID- 11240731
TI  - New cytotoxics and non-cytotoxics in epithelial ovarian cancer.
AB  - Several new cytotoxic agents with activity in relapsed ovarian cancer are being
      combined with paclitaxel plus platinum as the first step to assess their impact
      in randomized trials against the standard treatment. These include topotecan,
      gemcitabine, epirubicin, and liposomal doxorubicin. Because of overlapping
      toxicities, there have been challenges in combining some of these agents in full
      dose with combination paclitaxel plus platinum. These have been overcome by use
      of sequenced administration. In addition to these new agents, novel non-cytotoxic
      drugs targeting specific signaling molecules or the tumor microenvironment
      provide additional avenues for clinical investigation. Many of these agents are
      rational to assess in ovarian cancer where laboratory research has pinpointed a
      number of alterations in molecules involved in cell signaling and cell cycle
      control. Examples include the antibody to HER 2/neu, agents targeting protein
      kinase C alpha, the p53 gene, and matrix metalloproteinase inhibitors. The
      challenges facing their assessment include how to determine adequate dosing when
      toxic effects are minimal and how to assess evidence of antitumor activity, short
      of conducting randomized studies. Finally, how best to use such agents together
      with conventional chemotherapy, in combination or in sequence, is unknown. Large
      clinical studies with some of these agents will provide some answers to their
      impact and how best to use them in the first-line management of advanced
      epithelial ovarian cancer.

PMID- 11240732
TI  - Long term survival of patients with advanced ovarian cancer treated with
      intraperitoneal radioimmunotherapy.
AB  - PURPOSE: To determine the long term survival of patients with advanced ovarian
      cancer treated with radioimmunotherapy following cytoreductive surgery and
      platinum based chemotherapy. PATIENTS AND METHODS: Eligibility criteria included
      patients with histological evidence of ovarian cancer stages IC-IV following
      completion of conventional platinum containing chemotherapy. Of 52 patients
      entered into the study, 31 had residual disease following standard chemotherapy
      and 21 patients had achieved complete remission. Treatment consisted of one
      intraperitoneal administration of 25 mg of monoclonal antibody HMFG1 labelled
      with 18 mCi/m2 of 90Y. Survival was the primary end-point. RESULTS: In the group
      of 21 patients who had achieved complete remission following surgery,
      conventional chemotherapy and intraperitoneal radioimmunotherapy, the median
      survival has not been reached with a maximum follow-up of 12 years. Survival at
      greater than 10 years is 78%. CONCLUSION: This study suggests that a substantial
      proportion of patients who achieve complete remission with conventional therapy
      can achieve a long-term survival benefit when treated with intraperitoneal
      radioimmunotherapy using HMFG1 labelled with 90Y.

PMID- 11240733
TI  - Options for modulation of drug resistance in ovarian cancer.
AB  - The objective of this paper is to present an update of mechanisms responsible for
      drug resistance in ovarian cancer and the possible therapeutic options to
      modulate this resistance using literature review with emphasis on data acquired
      in studies comprising ovarian tumor samples. The classic concepts on resistance
      in ovarian cancer, namely platinum and multidrug resistance, are briefly
      discussed, followed by a description of more recent insights concerning the role
      of apoptosis in the development of chemoresistance. A wide variety of mechanisms
      may be responsible for drug resistance in ovarian cancer. However, a growing body
      of evidence indicates that defects in the intra- and extracellular apoptotic
      pathways are an important cause of resistance to cytotoxic agents which opens
      several new treatment strategies.

PMID- 11240735
TI  - Advanced ovarian cancer: update, remarks and conclusions on optimal therapy.

PMID- 11240734
TI  - High dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) in
      ovarian cancer.
AB  - Ovarian cancer is a very chemosensitive tumor, but survival is poor due to the
      emergence of drug resistance. It may be possible to overcome resistance by using
      high dose chemotherapy supported by peripheral blood stem cell transplantation. A
      review of retrospective studies of dose-intensity and phase I/II high dose
      chemotherapy trials, and an analysis of the EBMT registry data is used as
      evidence to support the case for dose-intensification in ovarian cancer. As a
      result of this analysis there are now prospective randomized trials of high dose
      chemotherapy in ovarian cancer.

PMID- 11240736
TI  - The antibody response to HPV proteins and the genomic state of HPVs in patients
      with cervical cancer.
AB  - Human papillomavirus (HPV) DNAs are often found to be integrated into the human
      genome in high-grade cervical intraepithelial neoplasia (CIN) as well as in
      invasive cervical cancers. Investigation of the relationship between the genomic
      status of specific HPV genes and their antibody responses to the virus-like
      particles (VLPs) of HPV-16 L1/L2 proteins and the in vitro translated HPV-16 E6
      and E7 proteins may help to illustrate the mechanism of HPV-related cervical
      carcinogenesis and host immune response. Cervical cancer tissues obtained from 39
      patients were studied to evaluate the physical status of HPV genes by Southern
      blotting, DNA-PCR, and RT-PCR of E2. The antibody response against the HPV-16
      L1/L2 VLPs of serum specimens were tested by ELISA and the antibody response
      against the HPV-16 E6 and E7 proteins were tested by radioimmunoprecipitation
      assay (RIPA), respectively. Integrated forms of HPV-16 DNA were found in 23 of
      the 38 patients (60.5%). The HPV-16 positive cervical cancer patients showed a
      significantly higher prevalence rate (39.5%; 15/38) of antibodies to HPV-16 L1/L2
      VLPs than that of the control group (8.7%; 2/28) (P < 0.05). Antibodies to HPV-16
      L1/L2 VLPs were more commonly detectable in cervical cancer patients having the
      episomal form of HPV-16 DNA (pure episomal and mixed forms) (60%; 9/15) than in
      those who had only the integrated forms of HPV-16 DNA (26.1%; 6/23) (P < 0.05).
      Antibodies to E6 and E7 proteins were positive in 36.8% (14/38) and 50% (19/38)
      of the patients with HPV-16 positive cervical cancer, respectively. These were
      significantly higher than the positive rates for the control group (8.3% and
      2.8%) (P < 0.05). The differences between sero-reactivities to E6 and E7 proteins
      in the patients with episomal forms of HPV-16 DNA and those with integrated forms
      of HPV-16 DNA were not statistically significant (P > 0.05). Integrated forms of
      HPV-16 DNA were prevalent in most patients with cervical cancer in Korea.
      Antibodies to HPV-16 L1/L2 VLPs, in vitro translated HPV-16 E6 and E7 proteins,
      appeared in a significantly larger proportion of the HPV-associated cervical
      cancer patients than in the controls. Antibodies to HPV-16 L1/L2 VLPs were more
      often detected in cervical cancer patients having the episomal form of HPV-16 DNA
      than in those having only integrated forms of HPV-16 DNA. Antibody responses to
      HPV-16 E6 and E7 proteins were not influenced by the different viral states.

PMID- 11240737
TI  - Palliative chemotherapy in recurrent carcinoma of the cervix: an audit of the use
      of ifosfamide and review of the literature.
AB  - A review was conducted on 34 patients treated with intravenous ifosfamide for
      relapsed, inoperable carcinoma of the cervix between 1988 and 1996. The median
      age of patients was 44 years. Thirty-two patients had squamous cell carcinoma and
      2 had adenocarcinoma. Radiotherapy had been used in primary management in 33, neo
      adjuvant platinum chemotherapy in 7, and previous palliative chemotherapy in 11.
      Symptomatic response was assessed with respect to the symptom requiring
      palliaton. 25 patients failed to complete 6 cycles of chemotherapy: due to
      progressive disease in 14, lack of symptom response in 2, and toxicity in 11 of
      whom 7 had encephalopathy sufficient to abandon treatment. 32 patients were
      evaluable for objective response. Pathologic complete response (CR) was achieved
      in 1 patient, and partial response (PR) was achieved in 3 patients. The objective
      response rate was 11.8%. Symptomatic response throughout treatment occurred in 8
      patients (24%); objective response was seen in only 3 (1 CR, 2 PR) of them and
      progressive disease in the remaining 5. Response duration in the 4 objective
      responders was 25 months in the patient with CR and 4, 6 and 8 weeks in the 3
      patients with PR. In conclusion, ifosfamide, as given, is associated with
      unacceptable toxicity and insufficient symptomatic efficacy for use as a
      palliative treatment in patients with relapsed carcinoma of the cervix.

PMID- 11240738
TI  - Survival of patients with adenocarcinoma of the uterine cervix in western Sweden.
AB  - Survival in adenocarcinoma of the uterine cervix varies between different
      reports. In our study the patients have been treated in a similar way as those
      with squamous cell carcinoma. One hundred twenty-one adenocarcinomas were
      diagnosed between 1987 and 1994 in the West Sweden Health Care Region. One
      hundred of the patients with adenocarcinoma were treated at Sahlgrenska
      University Hospital and studied retrospectively. The median age was 54 years
      (range 27-91). Histopathologic differentiation was relatively evenly distributed
      between well (34%), intermediately (38%), and poorly differentiated (28%). All
      FIGO stages were represented, but stage I predominated (65%). Depending mainly on
      tumor stage and age, the patients had either surgery, surgery + radiotherapy, or
      radiotherapy only. In our study, the five-year survival for adenocarcinoma was
      64% and for squamous/adenosquamous carcinoma was 66% (NS). The five-year survival
      for different stages of adenocarcinomas was for stage I 86%, stage II 38%, stage
      III 23%, and stage IV 0%, the difference between stage I and stage II being
      highly significant. Treated in a similar way, the five-year survival for
      adenocarcinoma is equal to that for squamous/adenosquamous carcinoma in our
      study.

PMID- 11240739
TI  - Selected epidemiological time trends of vulvar carcinoma in Israel.
AB  - Recently, considerable demographic changes have occurred in Israel. The purpose
      of the present population-based nationwide epidemiological study of carcinoma of
      the vulva was to assess changes over time in incidence, relative frequency, age
      pattern and ethnic distribution. The study group included all 257 Jewish females
      with histologically confirmed neoplasms of the vulva diagnosed in Israel during
      the ten year period from 1985 to 1994. Data were obtained from the Israeli Cancer
      Registry and compared with data from a previous study covering a 13 year period
      (1961 to 1973). The relative frequency of carcinoma in situ (CIS) of the vulva
      increased significantly during the later period (from 5.4% to 12.8%), while that
      of invasive vulvar carcinoma declined significantly (from 80.6% to 69.6%).
      Regarding invasive vulvar carcinoma, a significant decrease in the age-adjusted
      standardized rates and in the mean annual incidence rate in the 70+ age group was
      found. The ethnic distribution pattern of invasive vulvar carcinoma did not
      change and remained similar to that of cervical carcinoma, namely a trend for
      higher incidence among women born in North Africa. The increased frequency of
      vulvar CIS is attributed mainly to a greater propensity to perform vulvar
      biopsies. The possibility of a consequent decline of vulvar carcinoma cannot be
      ruled out.

PMID- 11240740
TI  - Are adenocarcinomas and adenosquamous carcinomas different from squamous
      carcinomas in stage IB and II cervical cancer patients undergoing primary radical
      surgery?
AB  - The aim of this study was to define clinicopathologic features and to investigate
      prognostic factors in early-stage cervical adenocarcinomas and adenosquamous
      carcinomas in patients undergoing primary radical surgery. One hundred thirty
      four patients with stage IB or II cervical adenocarcinoma or adenosquamous
      carcinomas treated at a single institution were reviewed and compared to squamous
      carcinomas (N = 757) treated in the same period. Among adeno-adenosquamous
      carcinomas, stage II disease, parametrial extension, and deep cervical stromal
      invasion (>2/3) were associated with increased risk of pelvic lymph node
      metastases, while only clinical stage II, DNA index >1.3 (by flow cytometry), and
      pelvic node metastases were significantly associated with decreased survival by
      multivariate analyses. The five-year recurrence-free and overall survival rates
      of patients with adeno-adenosquamous vs squamous carcinoma were 72.2% vs 81.2% (P
      = 0.0109), and 74.1% vs 82.8% (P = 0.0136), respectively by Mantel-Cox test.
      After controlling confounding factors, histologic type (adeno-adenosquamous vs
      squamous) was confirmed as an independent prognostic factor for recurrence-free
      survival [relative risk (RR): 1.2792; 95% confidence interval (CI): 1.0628
      1.5399, P = 0.0092) and overall survival (RR: 1.2594, 95% CI: 1.0467-1.5155, P =
      0.0146) in the whole series (N = 891). Although pattern of relapse by histologic
      type was not significantly different, patients with recurrent adeno-adenosquamous
      carcinoma did significantly worse than those with recurrent squamous carcinoma.
      In conclusion, the prognosis of adeno-adenosquamous carcinoma of the cervix is
      slightly worse than squamous tumors. Since salvage of recurrent adeno
      adenosquamous carcinoma after primary radical surgery is generally ineffective
      using conventional treatment, innovative strategies are necessary for the high
      risk group after primary surgery and all recurrent adeno-adenosquamous carcinomas
      regardless of size or site.

PMID- 11240741
TI  - Adenosarcoma of the uterus: a clinicopathologic, DNA flow cytometric, p53 and mdm
      2 analysis of 11 cases.
AB  - Eleven patients with uterine adenosarcoma diagnosed between 1970 and 1995 were
      evaluated according to DNA ploidy, S-phase fraction, p53 and mdm-2 expression,
      and traditional clinical and pathological prognostic factors, such as tumor
      stage, grade and mitotic index. DNA flow cytometric analysis and
      immunohistochemical staining for p53 and mdm-2 were performed on paraffin
      embedded archival tissue from the uterine tumors. The patients ranged in age from
      41 to 90 years (median, 76 years). Only one patient was premenopausal at the time
      of diagnosis and five (45%) were nulliparous. One patient had received previous
      pelvic irradiation for anal squamous carcinoma. Six of the tumors (55%) were pure
      adenosarcoma and five (45%) were adenosarcoma with sarcomatous overgrowth. Nine
      patients had a stage I tumor and two had a stage II tumor. Among the six
      adenosarcomas we found three DNA diploid tumors, two DNA aneuploid tumors, and
      one DNA multiploid tumor. All adenosarcomas had an S-phase fraction less than
      10%, except one that was not assessable. None was p53 positive and only one
      overexpressed mdm-2. All five adenosarcomas with sarcomatous overgrowth were DNA
      aneuploid, three (60%) had an S-phase fraction > 10%, two (40%) were p53
      positive, and one (20%) overexpressed mdm-2. Five of the eleven patients suffered
      recurrences, and three (60%) of these developed lung metastases. During the
      observation period four (36%) patients (2 adenosarcomas and 2 adenosarcoma with
      sarcomatous overgrowth) died of disease, three patients died of intercurrent
      disease without recurrence, and the remaining four are alive with no evidence of
      disease. The overall five-year survival rate for all stages was 69%; for patients
      with AS it was 80%, while for those with adenosarcoma with sarcomatous overgrowth
      it was 50%. There were no variables which correlated with survival. In
      conclusion, we found hat the typical adenosarcoma had a tendency to be of low
      stage, have a lower mitotic rate and an S-phase fraction <10%. On the other hand,
      adenosarcomas with sarcomatous overgrowth were of high grade, had a high mitotic
      rate, and were DNA aneuploid with an S-phase fraction >10%. None of the variables
      studied correlated with survival. Tumors that were p53-positive or overexpressed
      mdm-2 did not behave worse than their negative counterpart. All patients who
      recurred with distant metastases died of disease.

PMID- 11240742
TI  - Long-term results and pharmacokinetics of high-dose paclitaxel in patients with
      refractory epithelial ovarian carcinoma.
AB  - The purpose of this study was to analyze the efficacy and toxicity of a high dose
      of paclitaxel in patients with ovarian cancer refractory to platinum
      chemotherapy. Another phase II study of hydroxyurea was run in the same patient
      population. Fifty patients with measurable ovarian cancer were entered on this
      phase II study at The University of Texas M. D. Anderson Cancer Center. Treatment
      consisted of 250 mg/m2 of paclitaxel given by continuous intravenous infusion
      over 24 h every 3 weeks. Patients with disease unresponsive to paclitaxel could
      then be crossed over to hydroxyurea, and vice versa. Twenty-five (53%) out of 47
      evaluable patients had a response (two complete responses and 23 partial
      responses). Twelve (26%) patients had stable disease. The median survival was
      11.3 months. The main toxic effect was neutropenia (98% of patients) with 28 (9%)
      episodes of neutropenic fever. Neutropenia required therapy with granulocyte
      colony-stimulating factor. Other side effects were alopecia (100%), anemia (98%),
      gastrointestinal problems (57%), stomatitis (27%), and neurotoxicity (55%).
      Paclitaxel administered at a high dose as a single agent proved to be very active
      in patients who had platinum-refractory ovarian cancer and was well tolerated.
      Further studies of high-dose paclitaxel in patients with ovarian carcinoma are
      indicated.

PMID- 11240743
TI  - Radical cytoreductive surgery combined with platinums-carboplatin and cisplatin
      chemotherapy for advanced ovarian cancer.
AB  - In an attempt to improve the therapeutic outcome for patients with advanced
      ovarian cancer, primary radical cytoreductive surgery consisting of hysterectomy,
      bilateral salpingo-oophorectomy, omentectomy and retroperitoneal lymph node
      resection, with optimal cytoreduction in case of metastatic lesions, was followed
      by five courses of chemotherapy of carboplatin 280 mg/m2 i.v. on day 1 and
      cisplatin 70 mg/m2 i.v. on day 2, every four weeks. A total of 51 patients with
      advanced epithelial ovarian cancer comprised the study (6 with stage IIC, 32 with
      stage III, and 13 with stage IV). Following radical cytoreductive surgery, 29
      patients (57%) showed 2 cm or less of residual disease. There was a low incidence
      of severe complications and no postoperative mortality. An overall response rate
      of 76% of patients consisting of 42% pathologic complete response and 34% partial
      response was observed. The overall four-year survival rate for patients with
      stage III cancer was 70%. The dose-limiting toxicity was identified to be
      hematologic toxicity, which showed grade 3/4 of leuopenia 37% (neutropenia 73%)
      and thrombocytopenia 24%. The incidence of peripheral neurotoxicity was
      comparatively low. An evaluation of nerve conduction velocity revealed that motor
      neurotoxicity was liable to appear in the lower extremity, while sensory nerve
      damage was often noted in the periphery in both the upper and lower extremities.
      The combined chemo-surgery treatment resulted in good response and good survival
      without fatal toxicity for patients with advanced ovarian cancer.

PMID- 11240744
TI  - Plasminogen activators and inhibitors in ovarian adenocarcinomas.
AB  - The fibrinolytic process was examined in cultures from malignant epithelial
      ovarian tumors and compared to normal ovarian tissue. The fibrinolytic enzymes,
      urokinase plasminogen activator (uPA) antigen and activity, tissue plasminogen
      activator (tPA) antigen and activity, plasminogen activator inhibitor 1 (PAI-1)
      and plasminogen activator inhibitor 2 (PAI-2) antigen were measured in short-term
      primary cultures at weekly intervals over a 3-week period. The cultures comprised
      of 15 ovarian adenocarcinomas and 12 normal ovarian tissue samples. The
      concentration of uPA antigen (p < 0.01) and activity (p < 0.01) and (p < 0.05)
      levels were higher in malignant specimens on all 3 count days. Activity levels of
      tPA were elevated significantly in malignant specimens on days 7 and 21 (p <
      0.05). No significant difference was found between PAI-1 levels. PAI-2 antigen
      levels were significantly higher in the tumor specimens on days 14 and 21 (P <
      0.01). These data indicate that uPA may have a significant role in the biology of
      ovarian cancer and may be an important factor in early tumor spread. Further work
      is required on the effects of intervention in this biological process.

PMID- 11240745
TI  - Analysis of microsatellite instability in cervical cancer.
AB  - Microsatellite instability was first reported in hereditary nonpolyposis
      colorectal cancer (HNPCC) as well as other cancers, including endometrial and
      ovarian cancers. Single base repeat markers of human MSH3 and MSH6 genes were
      found to precipitate the action of human MSH2. The marker BAT-26 was reported to
      be a simple, low-cost, and rapid marker for detection replication errors (RER)
      and the status of colorectal cancers. We analyzed di-nucleotide repeats of the
      microsatellite markers (D2 S123, D5 S82, D5S299, D10S197, D17S791, D18S34),
      single base repeat markers (DeltaP3, hMSH3, hMSH6, and TGFbeta-RII), and BAT-26
      to evaluate microsatellite instability in cervical cancer. Altogether 80 paired
      cervical cancers were studied. Our results showed that microsatellite instability
      is not common in cervical cancer, and the mutation of the single base repeat of
      mismatch repair (MMR) genes (hMSH3 and hMSH6) is also uncommon. The BAT-26 is not
      a good marker to detect the RER status of cervical cancer.

PMID- 11240746
TI  - Mean nuclear volume: a supplementary prognostic factor in endometrial cancer.
AB  - We evaluated the following nine parameters with respect to their prognostic value
      in females with endometrial cancer: four stereologic parameters [mean nuclear
      volume (MNV), nuclear volume fraction, nuclear index and mitotic index], the
      immunohistochemical expression of cancer antigen (CA125) and the postsurgical
      stage (P-stage), the malignancy grade, the depth of myometrial tumor invasion and
      the age of the female. Tissue was obtained from 68 consecutive endometrial cancer
      patients with clinical FIGO stage I tumors who were registered in the Danish
      endometrial cancer study (DEMCA). The primary operation included total abdominal
      hysterectomy and bilateral salpingo-oophorectomy. All patients underwent radical
      operations. The tumors were classified postsurgically as P-stage I-III. All
      patients received the same postoperative radiation therapy. The surviving
      patients were observed for a median of 6.4 years (range 5.0-8.4 years). Cox
      regression analysis (automatic forward selection) showed the MNV to be the most
      significant prognostic parameter followed by the P-stage. Patients who had
      localized tumors or tumors with small nuclei had a better probability of
      surviving than did women with advanced tumors or tumors with large nuclei. No
      significant relationship between survival and the remaining seven parameters was
      demonstrated. This first investigation of the prognostic value of the MNV in
      females with endometrial cancer demonstrates that it may assist the distinction
      between those patients who can be cured by hysterectomy alone and those who need
      adjuvant therapy.

PMID- 11240747
TI  - Octreotide induced remission of a refractory small cell carcinoma of the
      endometrium.
AB  - This is the first report of remission obtained with octreotide in a woman
      diagnosed with recurrent small cell carcinoma of the endometrium with
      neuroendocrine features, refractory to a combination of etoposide, cisplatin, and
      radiation therapy. Stabilization of disease was obtained with a combination of
      tamoxifen and leuprolide depot. Regression of disease was then achieved by the
      addition of octreotide. The use of octreotide as an antitumor agent is reviewed.

PMID- 11240748
TI  - Does lichen sclerosus play a central role in the pathogenesis of human
      papillomavirus negative vulvar squamous cell carcinoma? The itch-scratch-lichen
      sclerosus hypothesis.
AB  - In the past decade, two types of vulvar squamous cell carcinoma (SCC) have been
      delineated, Human papillomavirus (HPV) positive and negative. Clinicopathologic,
      virologic, cytomorphometric, and genetic differences support the view that these
      two types of carcinoma are fundamentally different and that HPV-negative
      carcinoma is not simply carcinoma where viral DNA has not been able to be
      identified. The traditional view of HPV-negative carcinoma is that it is caused
      by chronic tissue damage from itching and scratching. However, itching and
      scratching alone do not explain the close association of carcinoma with lichen
      sclerosus, nor the absence of such an association with other itchy conditions
      such as eczema or psoriasis. These observations point to a role for lichen
      sclerosus in the pathogenesis of vulvar carcinoma. Most observations about the
      etiology of lichen sclerosus can be grouped into its immunogenetic or genital
      predisposition, or the Kobner phenomenon. In the itch-scratch-lichen sclerosus
      hypothesis, lichen sclerosus is postulated to occur as a Kobner phenomenon in
      women with the susceptible immunophenotype who scratch because of genital
      irritants such as urine, vaginal secretions and smegma, and psychological
      factors. Lichen sclerosus, itself a very itchy condition, contributes to a
      vicious cycle of itching and scratching which leads to superimposed lichen
      simplex chronicus, squamous cell hyperplasia, and ultimately carcinoma. The itch
      scratch-lichen sclerosus hypothesis reconciles the traditional itch-scratch
      hypothesis with the strong clinicopathologic association of lichen sclerosus with
      carcinoma.

PMID- 11240749
TI  - Endometrial stromal sarcoma of the uterus: a clinicopathologic, DNA flow
      cytometric, p53, and mdm-2 analysis of 17 cases.
AB  - Seventeen patients with endometrial stromal sarcoma (ESS) diagnosed between 1970
      and 1996 were evaluated according to DNA ploidy, S-phase fraction (SPF), p53, and
      mdm-2 expression, as well as traditional clinical and pathologic prognostic
      factors, such as tumor stage, grade, and mitotic index. DNA flow cytometric
      analysis and immunohistochemical staining for p53 and mdm-2 were performed on
      paraffin-embedded archival tissue from the uterine tumors. Flow cytometric DNA
      histograms were obtained from 16 patients. The patients ranged in age from 41 to
      78 years (median, 57 years). Seven (41%) patients were premenopausal. Thirteen
      low-grade ESS were DNA diploid and had a low SPF. Of these, two overexpressed
      p53, while only one was mdm-2 positive. Among the four high-grade ESS we found
      one (25%) DNA diploid tumor and three (75%) DNA aneuploid tumors. Two (50%) had
      an SPF greater than 10%, three (75%) were p53-positive, and two (50%)
      overexpressed mdm-2. During the observation period, nine (53%) patients (five
      with low-grade and four with high-grade tumors) died of disease. The 5-year
      survival rate for patients with low-grade ESS was 74%, while all four patients
      with high-grade ESS died of disease within 14 months of diagnosis. Using the log
      rank test, we found a significant correlation between survival and tumor grade (P
      = 0.007), DNA ploidy (P = 0.026), SPF (P = 0.048), and FIGO surgical stage (P =
      0.026). In conclusion, we found that tumor grade was a strong predictor of
      clinical outcome in ESS. In addition, a worse prognosis was found for those ESS
      patients with advanced disease, DNA aneuploidy, and a high SPF. There was no
      difference between the recurrent and nonrecurrent group of early stage (surgical
      stage I), low-grade ESS with regard to clinicopathological features, DNA ploidy,
      SPF, p53, and mdm-2 expression. All patients with high-grade ESS died of disease
      within 14 months of diagnosis. In contrast, only three of the 11 patients with
      early stage, low-grade ESS died of disease.

PMID- 11240750
TI  - Brachytherapy for early endometrial carcinoma: a comparative study with long-term
      follow-up.
AB  - The current study was undertaken to evaluate the effect of preoperative uterine
      or postoperative vaginal brachytherapy compared to no adjuvant therapy on the
      disease-free interval, sites of recurrence, and survival in favorable stage IB
      endometrial carcinoma. One hundred and forty-six patients with FIGO grade 1 and 2
      endometrial carcinoma and 1-33% myometrial invasion treated between 1974 and 1992
      were retrospectively studied. The use of brachytherapy varied among the treating
      physicians during the study period. A Kaplan-Meier survival analysis was used to
      estimate disease-free survival and differences between treatment groups were
      evaluated with the Mantel-Cox statistic. Recurrent disease occurred in 7 patients
      (5.3%). Vaginal recurrences accounted for 6 of the 7 sites of recurrences.
      Recurrences occurred in 1.3% of grade 1 vs. 8.7% of grade 2 tumors (P = 0.04).
      Among 69 grade 2 tumors, recurrences occurred in 7.5% of those treated with
      brachytherapy vs. 10.3% of those not treated (P = 0.68). Brachytherapy did not
      affect the disease-free or overall survival. No serious complications directly
      related to therapy occurred. Vaginal recurrences occur even in early endometrial
      carcinoma. This study demonstrates no apparent benefit to brachytherapy. A larger
      study would be required to see a recurrence or survival difference.

PMID- 11240751
TI  - A pharmacokinetic and clinical evaluation of thio-TEPA in combination with
      cisplatin as first-line chemotherapy for advanced epithelial ovarian carcinoma.
AB  - The purpose of the study was to explore the combination of thio-TEPA with
      cisplatin in first-line chemotherapy of epithelial ovarian cancer with special
      reference to pharmacokinetic and pharmacodynamic relationships. Ten women with
      advanced disease were included. Pharmacokinetics of thio-TEPA were similar to
      those in previous studies of single drug therapy with rapid first order
      elimination of the parent drug and substantial intra- and interindividual
      variation of the area under the concentration-time curve (AUC). No effects of the
      drug sequence or repeated treatments were seen on the pharmacokinetics of thio
      TEPA, indicating no significant influence from the coadministration of cisplatin
      on the distribution, metabolism or excretion of thio-TEPA. Pharmacokinetic-
      pharmacodynamic relationships were less pronounced compared to previous studies,
      probably due to the influence from cisplatin. Prolongation of treatment
      intervals, dosage reduction, and withholding of thio-TEPA were required due to
      myelosuppression, which was the dominating toxicity. Non-hematological toxicity
      was moderate and easily manageable, cisplatin-related toxicity did not seem to be
      aggravated. Response rate based on CA 125 fluctuations was 80%, overall median
      survival was 18 months. In conclusion, the pharmacokinetics of thio-TEPA does not
      seem to be significantly influenced by concomitant administration of cisplatin in
      female patients. Manageable toxicity, largely restricted to myelosuppression, and
      high response rate justify further evaluation of the current regimen.

PMID- 11240752
TI  - The role of 18F-fluoro-deoxyglucose positron emission tomography (18F-FDG PET) in
      diagnosis of ovarian cancer.
AB  - We evaluated the clinical significance of 18F-FDG PET to detect malignant ovarian
      neoplasms and tumor spread. 40 patients (median age: 57.5 years) underwent
      laparotomy because of clinical suspicion of malignant ovarian tumors or recurrent
      disease. The results of the preoperatively performed PET were correlated with the
      postoperative histologic diagnosis and the intraoperatively assessed tumor
      spread. In 10 of 40 patients benign tumors were found, among which a tubo-ovarian
      abscess was the only one diagnosed as false positive. 4/30 malignant neoplasms
      did not originate from the coelomic epithelium, but all were correctly recognized
      as malignant tumors by PET, as was recurrent ovarian cancer in 12 patients. Out
      of 14 primary ovarian carcinomas, 2 borderline tumors and 1 well-differentiated
      adenocarcinoma FIGO stage I were not correctly identified. Considering the tumor
      type, sensitivity, and specificity were 90%, calculating for the positive and
      negative predictive value 96% and 75%, respectively, and 90% for the diagnostic
      accuracy. Those statistical parameters were slightly lower for PET detection of
      lymph node metastasis and peritoneal carcinomatosis. Although its diagnostic
      accuracy may vary depending on the clinical application, 18F-FDG PET is basically
      a suitable method for detecting ovarian malignancies, particularly in patients
      with relapsed ovarian carcinoma.

PMID- 11240753
TI  - Immunohistochemical and mutational analysis of p53 tumor suppressor gene in
      gestational trophoblastic disease: correlation with mdm2, proliferation index,
      and clinicopathologic parameters.
AB  - The role of p53 in the pathogenesis of gestational trophoblastic disease (GTD)
      was investigated. Immunohistochemical studies for p53, its regulator mdm2, and
      proliferation marker Ki67 were performed on paraffin-embedded tissues of 28
      partial moles (PM), 57 complete moles (CM), 14 choriocarcinomas (CCA), and 31
      normal placentas. Three antibodies to p53 (DO-7, Ab-2, Ab-3) were used and
      demonstrated immunoreactivity for wild-type p53 protein predominantly in the
      nuclei of cytotrophoblasts. Direct DNA sequencing of 36 hydatidiform moles using
      frozen tissues confirmed an absence of mutational changes in exons 5-8. CCA was
      found to have the highest p53 protein expression, followed by CM, PM, and normal
      placenta (P < 0.001). In normal placentas (P = 0.0001), PM, and CM (P = 0.016),
      an inverse correlation between their gestational age and p53 expression was
      observed. p53 expression was found to correlate with proliferation index in
      normal placenta (P = 0.0001) and all three groups of GTD (P = 0.012). Significant
      correlation between p53 and mdm2 expression was also observed (P < 0.01). The
      distinctive expression of p53 wild-type protein in the cytotrophoblasts and its
      positive correlation with the proliferative index suggests that its
      overexpression in GTD may be related to its effect on cell proliferation. The
      parallel expression of mdm2 and p53 also supports the presence of an
      autoregulatory feedback loop in the control of this process. No correlation could
      be found between clinical progress of the patients with hydatidiform moles, and
      the p53 (P = 0.78) or mdm2 protein (P = 0.54) expression suggesting that neither
      of them carries any prognostic significance.

PMID- 11240754
TI  - Co-expression of p53 by epithelial and stromal elements in carcinosarcoma of the
      female genital tract: an immunohistochemical study of 19 cases.
AB  - Carcinosarcoma is an aggressive neoplasm of the female genital tract, which
      comprises 1-2% of malignancies of the uterine corpus. Because of the broad range
      of differentiation exhibited by these tumors, the precise nature of the
      relationship between epithelial and stromal components in this unique tumor
      remain unclear. Previous studies have demonstrated that mutation and consequent
      overexpression of the tumor suppressor gene p53 occurs frequently in
      carcinosarcoma and is conserved from primary to metastastic sites. We examined
      p53 accumulation in formalin-fixed, paraffin-embedded archival sections in 19
      cases previously shown to have mutations in the p53 gene and performed semi
      quantitative analysis of the intensity of staining and relative density of
      positive cells and stromal and glandular elements. There was a high level of
      concordance of immunohistochemical staining for the p53 oncoprotein between
      glandular and stromal elements. These results further suggest a clonal origin for
      the diverse elements of carcinosarcoma.

PMID- 11240755
TI  - Does ligation of the hypogastric artery at the time of radical hysterectomy and
      lymphadenectomy decrease blood loss? Results of a prospective randomized trial.
AB  - A prospective, randomized study of patients undergoing radical hysterectomy for
      gynecologic malignancies was undertaken from 10/95 to 11/96 to determine if
      ligation of the hypogastric arteries at the time of radical hysterectomy
      decreases blood loss. Patients were randomized to either ligation of the
      hypogastric artery (Group 1) or no ligation (Group 2) prior to a standard Piver
      type III radical hysterectomy. Surgeries were performed by Board certified
      gynecologic oncologists with gynecologic oncology fellows and/or OB/GYN
      residents. Patients were analyzed for demographic characteristics and
      intraoperative and postoperative parameters. Statistical analysis was performed
      with independent samples t-test, Mann-Whitney rank sum test, Chi square and
      Fisher exact test. Twenty-one patients were randomized to group 1 and 22 to group
      2. Groups were similar with respect to demographics and preoperative parameters
      except for age. There were no differences among the groups with respect to
      intraoperative and postoperative parameters. The mean estimated blood loss for
      group 1 was 600 ml and 550 ml for group 2 (P = NS). Hypogastric artery ligation
      (HAL) at the time of radical hysterectomy for gynecologic malignancy does not
      reduce blood loss.

PMID- 11240756
TI  - Noninvasive detection of inguinofemoral lymph node metastases in squamous cell
      cancer of the vulva by L-
AB  - In the majority of patients with early stage squamous cell cancer (SCC) of the
      vulva, an inguinofemoral lymphadenectomy is performed (in retrospect) for
      diagnostic reasons: exclusion of inguinofemoral lymph node metastases. The
      morbidity of this procedure, however, is significant. The aim of the present
      study was to evaluate noninvasive detection of inguinofemoral lymph node
      metastases by positron emission tomography (PET) using L-[1-11C]-tyrosine (TYR)
      as tracer. In patients with SCC of the vulva, scheduled for resection of the
      primary tumor and uni- or bilateral inguinofemoral lymphadenectomy, results of
      preoperative palpation of the groins and TYR-PET imaging were compared with
      histopathology. PET imaging was performed using two different methods. In a first
      group (n = 16), nonattenuation corrected 'whole body' scans were performed, and
      in a second group (n = 9), attenuation corrected static emission scans.
      Sensitivity, specificity, accuracy, and positive and negative predictive value
      for palpation were 62%, 89%, 82%, 67%, and 87% per groin. Sensitivity,
      specificity, accuracy, and positive and negative predictive value for TYR-PET
      were calculated for the two methodologies separately and overall. There were no
      significant differences. Overall values were 53%, 95%, 94%, 33%, and 98% per
      lymph node and 75%, 62%, 65%, 41% and 88% per groin. Detection of inguinofemoral
      lymph node metastases by TYR-PET is not superior to palpation. Neither palpation
      nor TYR-PET is able to adequately predict or exclude presence of inguinofemoral
      lymph node metastases in patients with SCC of the vulva.

PMID- 11240757
TI  - LOH of chromosome 6q compared with LOH of 17q and 18q in ovarian cancers:
      relationship to p53 expression and clinicopathological findings.
AB  - In 41 ovarian epithelial tumors (7 borderline and 34 invasive), loss of
      heterozygosity (LOH) of chromosomes 6q, 17q, and 18q was examined using 4
      microsatellite markers: ER (6q 25-1), BRCA1 (17q21), DCC (18q21), and D18S58
      (18q23). The LOH was compared with clinicopathological findings, including p53
      and ER expression. In borderline tumors, LOH and p53 expression were never found,
      while in invasive carcinomas LOH and p53 were found in 71% and 59% of cases,
      respectively. In particular, in invasive carcinomas 6q LOH represented a marker
      distinguishing two groups of tumors; those with 6q LOH were only of serous
      histotype and at advanced stages (III/IV). No significant difference was found
      for any of genes in 5-year survival of the patients. No correlation was found
      between ER expression and ER LOH, as well as between biological aggressiveness
      and 17q and/or 18q LOH. We conclude that p53 and LOH of the investigated loci
      distinguish borderline from invasive ovarian carcinomas; moreover, the comparison
      of these results with clinicopathological parameters suggests that the presence
      of 6q LOH may be a factor accounting for greater biologic aggressiveness
      independent of the histologic subtype.

PMID- 11240758
TI  - Effective desensitization protocol to paclitaxel following hypersensitivity
      reaction.
AB  - The objective of this paper is to describe our experience with a desensitization
      protocol to paclitaxel using the original paclitaxel solution in patients
      following severe hypersensitivity reactions. A retrospective review of 75
      consecutive patients with ovarian cancer who received intravenous paclitaxel
      based chemotherapy between January 1996 and May 1998 at the Gynecologic Oncology
      Unit at Meir Hospital-Sapir Medical Center, Kfar-Saba, Israel. All patients who
      developed a hypersensitivity reaction to paclitaxel were treated with a
      desensitization protocol. The protocol included serial 10-fold dilutions (up to
      1:100,000) of the actual paclitaxel infusate, delivered in successive volumes of
      1, 2, 4, and 8 ml. These escalating doses of paclitaxel were given intravenously
      at 15-min intervals for each dilution. Following administration of the last
      diluted dose, the patient received a 1-ml dose of the undiluted solution. If no
      side effects were recorded, the rest of the actual dose was delivered at a 3-h
      infusion rate. Vital signs were monitored and recorded throughout the course of
      treatment. Six patients with a previous paclitaxel-associated hypersensitivity
      reaction were successfully treated with the desensitization protocol. In
      conclusion, we demonstrate that the desensitization protocol is feasible and safe
      without compromising cytotoxic activity. Our results show that this strategy is a
      reasonable choice in this clinical setting and potentially avoids paclitaxel
      based regimen interruption.

PMID- 11240759
TI  - CD44v6 expression is an independent prognostic factor in node-negative FIGO stage
      IB cervical carcinoma.
AB  - Adhesion molecules such as CD44 play an important role in the metastatic cascade
      by mediating tumor cell interaction with the endothelium and the subendothelial
      matrix. As a so-called "lymphocyte homing receptor," CD44 is physiologically
      involved in migration of circulating lymphocytes to lymphatic tissue. In the
      present study, we investigated the expression of CD44v3 and v6 in 237 patients
      with stage IB, N0 cervical carcinoma by means of immunohistochemistry. These
      results were correlated with the GOG score and other prognostic variables. Median
      follow-up was 82.6 months (39-110 months). Thirty-nine patients recurred and 35
      died from disease within the observation period. In univariate analysis, the GOG
      score, histologic subtype, and CD44v6 expression were statistically significant
      predictors for poor overall survival (OS). In multivariate (Cox regression)
      analysis, the GOG score (< 40 vs. 40-120, RR: 1.37 (95% CI: 1.10-1.71); 40-120
      vs. > 120, RR: 2.23 (95% CI: 1.28-3.88); P = 0.004), histologic subtype
      (adenosquamous carcinomas) (RR: 4.56 (95% CI: 1.49-13.92), P = 0.007) and CD44v6
      expression (RR: 2.42 (95% CI: 1.14-5.10), P = 0.021) were independent predictors
      for poor OS. The expression of CD44v3 did not correlate with prognosis.
      Furthermore we found a strong correlation between CD44v6 expression and
      lymphovascular space invasion (LVSI) (chi2 = 17.01, P = 0.0001). Tumor expansion
      into the loco-regional lymphatic system is the preferred way of tumor spread in
      cervical carcinoma. The strong correlation of CD44v6 with LVSI produces a
      significant degree of suspicion that cervical carcinoma cells expressing CD44v6
      could, by mimicking lymphocytes, exploit their pathways.

PMID- 11240760
TI  - Pregnancy outcome after treatment with etoposide (VP-16) for low-risk gestational
      trophoblastic tumor.
AB  - The aim of this study was to evaluate subsequent fertility and pregnancy in
      patients treated for persistent trophoblastic tumors with single-agent VP-16.
      Records of all patients treated for persistent trophoblastic tumors at the Chiba
      University Hospital between January 1, 1986 and December 31, 1997 were reviewed.
      Of these, 85 patients were initially treated with single-agent VP-16. Subsequent
      pregnancy outcome of these patients was investigated. After remission with VP-16,
      36 patients (92.3%) of those who wished for a pregnancy (45.9% of all patients
      studied) conceived, and 91.7% had at least one live birth. A total of 56
      conceptions resulted in 42 (75.0%) term live births, seven (12.5%) first
      trimester spontaneous abortions, one (1.8%) second-trimester spontaneous
      abortion, four (7.1%) therapeutic abortions, and two (3.6%) repeated moles. There
      were no congenital anomalies, no stillbirths, and the neonates' physical growth
      was comparable to that of the standard population in Japan. Single VP-16 regimen
      for patients with low-risk gestational trophoblastic tumor appears to have no
      adverse effects on fertility potential and pregnancy outcome.

PMID- 11240761
TI  - Primary serous adenocarcinoma of the retroperitoneum with a response to platinum
      based chemotherapy: a case report.
AB  - A CAT-scan-guided biopsy of the retroperitoneal tumor of a 54-year-old female
      revealed a serous adenocarcinoma resembling a serous adenocarcinoma of ovarian
      origin. Partial response to platinum-based chemotherapy was observed. Exploratory
      laparotomies and an autopsy found no possible primary lesion for the tumor.
      Therefore, we concluded that this tumor is a primary serous adenocarcinoma of the
      retroperitoneum. Although further accumulation of cases is required, it appears
      that primary treatment for serous adenocarcinoma of the retroperitoneum is
      platinum-based chemotherapy if surgical removal is incomplete.

PMID- 11240762
TI  - Human papillomavirus presence and survival.

PMID- 11240763
TI  - Human papillomavirus presence and survival.

PMID- 11240764
TI  - Infection and cervical intraepithelial neoplasia.
AB  - The impact of sexually transmitted diseases (STDs) on the development of cervical
      intraepithelial neoplasia (CIN) has been increasingly recognized over the last 20
      years. Much attention has been focused on human papillomavirus (HPV) and the
      potential for screening for certain HPV types alongside standard cervical
      cytology in the hope of identifying those females at particular risk of
      developing high grade CIN or invasive carcinoma. Some infections, for example
      herpes simplex virus (HSV), have been heavily investigated in the past as they
      were thought to be involved in the development of CIN but were subsequently
      discounted. Also discounted as causes of CIN are Neisseria gonorrhoeae (NG) and
      Chlamydia trachomatis (CT). These infections were found to be associated with
      higher rates of CIN in early studies but transpired to be markers for the
      presence of other infections and pathology and therefore not themselves directly
      responsible for cytological changes. The role of bacterial vaginosis (BV) is the
      focus of several current investigations, not only in the genesis of CIN but also
      in the development of other gynecological and obstetric conditions and
      complications. Evidence to implicate Trichomonas vaginalis (TV) in the genesis of
      CIN is conflicting, but there is some evidence that it may exert its influence in
      a similar way to that hypothesized for BV, ie via abnormal amines. It is well
      known that there is a high level of concordance of STDs whereby the presence of
      one infection greatly increases the likelihood of there being one or more others
      present. There may be a synergism between some infections with regard to the
      causation of CIN, although the evidence for this is putative. Presented here is
      an overview of current and previous research in the field of lower genital tract
      infection as it relates to the development of CIN.

PMID- 11240765
TI  - Ploidy in human papillomavirus positive and negative vulvar squamous cell
      carcinomas and adjacent skin lesions.
AB  - To better characterize the two clinicopathologic types of squamous cell
      carcinoma, human papillomavirus (HPV) positive and negative, and their adjacent
      skin changes, we performed cytomorphometric analysis on 12 HPV-positive squamous
      cell carcinomas and adjacent vulvar intraepithelial neoplasia and 22 HPV-negative
      squamous cell carcinomas and adjacent squamous cell hyperplasia and lichen
      sclerosis. Our results were that 83% (10 of 12) HPV-positive carcinomas and 78%
      (7 of 9) adjacent vulvar intraepithelial neoplasia were aneuploid, compared with
      59% (13 of 22) HPV-negative carcinomas, 6% (1 of 16) squamous cell hyperplasias
      and 0% (0 of 20) lichen scleroses. Seventy-five percent (9 of 12) HPV carcinomas
      and 78% (7 of 9) vulvar intraepithelial neoplasias showed two aneuploid peaks,
      but no HPV-negative carcinoma or non-neoplastic epithelial lesion showed multiple
      aneuploid peaks. Fifty percent of squamous cell hyperplasias (8 of 16) and lichen
      scleroses (10 of 20) adjacent to HPV-negative carcinomas were hypodiploid. The
      mean DNA indices were: 1.70 for the dominant tumor cell population of HPV
      positive carcinoma, 1.64 for the dominant population of vulvar intraepithelial
      intraepithelial neoplasia, 1.41 for HPV-negative carcinoma, 0.85 for squamous
      cell hyperplasia and 0.83 for lichen sclerosis. In conclusion, the higher rate of
      aneuploidy, higher mean DNA index, and presence of multiploid peaks in HPV
      positive carcinomas and adjacent vulvar intraepithelial neoplasias compared with
      the lower rate of aneuploidy, lower mean DNA index, absence of multiploid peaks
      of HPV-negative carcinomas and tendency to hypodiploidy in squamous cell
      hyperplasia and lichen sclerosis support the hypothesis that there are two
      clinicopathologic types of vulvar carcinoma, with different pathogenetic
      mechanisms. The similarities in ploidy findings between vulvar HPV-positive
      carcinomas and vulvar intraepithelial neoplasia and those previously published
      for cervical carcinoma and cervical intraepithelial neoplasia support the view
      that these two cancers are analogous and have similar pathogenetic mechanisms.
      The frequent finding of hypodiploidy in squamous cell hyperplasia and lichen
      sclerosis next to HPV-negative carcinomas requires further investigation of the
      molecular pathogenesis of this cancer type.

PMID- 11240766
TI  - Laparoscopic abdominal staging in locally advanced cervical cancer.
AB  - In order to determine patterns of peritoneal spread in locally advanced cervical
      cancer, 59 patients with previously untreated stages IB and IIA tumor size > 4
      cm, IIB, III and IVA cervical cancer were considered for laparoscopic abdominal
      staging. Fifty-six patients (95%) were considered suitable and underwent
      laparoscopy. Peritoneal spread was found in 15 (27%) patients. The location was
      pelvic in nine (17%), extra-pelvic in one (2%), both pelvic and extra-pelvic in
      four (8%). Peritoneal washing was positive in five (9%) patients, being the
      unique site of peritoneal spread in one. Overall, 16 (29%) patients had evidence
      of abdominal disease. The median number of positive sites was one (range 1-4);
      uterine serosa was positive in nine (17%) patients, pre-vesical peritoneum in
      seven (13%), Douglas peritoneum in five (10%), paracolic gutter in three (6%),
      adnexa and omentum in two (4%), and sigmoid serosa in one (2%) patient. One
      operative complication occurred and all patients were discharged the day after
      the procedure. To date, with a median follow-up of 27 months (range 7-38), no
      metastasis has been detected at the trocar insertion sites. To summarize,
      laparoscopic staging in locally advanced cervical cancer is a safe, feasible and
      simple technique which is able to accurately detect abdominal disease.

PMID- 11240767
TI  - The prognostic significance of p53, mdm2, c-erbB-2, cathepsin D, and
      thrombocytosis in stage IB cervical cancer treated by primary radical
      hysterectomy.
AB  - The objective of this study was to evaluate the value of platelet count, p53,
      MDM2, c-erbB-2, and cathepsin D immunoreactivity as predictors of lymph node
      metastasis (LNM) as well as their prognostic significance in patients with stage
      IB cervical cancer treated by radical hysterectomy between 1991 through 1995. We
      also report on the outcome of a protocol considering lymph-vascular space
      invasion (LVSI) in addition to LNM as a strong motivation for adjuvant
      radiotherapy. A total of 93 patients were the subject of this retrospective
      study. The incidence of positive nodes was high (30.1%). Thrombocytosis (>/=
      400.000/mm3) was present in 6.7% of patients. Positive immunostaining was found
      for p53 (50.6%), MDM2 (21.7%), c-erbB-2 (14.5%), and cathepsin D (45.8%), but
      none of them was able to predict LNM. Only thrombocytosis was associated with an
      unfavorable prognosis: a statistically significant association was shown with
      relapse-free and overall survival in an univariate analysis (P = 0.0431 and P =
      0.0012, respectively) with a tendency to significance in multivariate analysis (P
      = 0.079 and P = 0.0882, respectively). We postulate that thrombocytosis in early
      stage cervical cancer could be a marker for subclinical tumor burden. LVSI,
      regarded as an indication for adjuvant radiotherapy, was no longer associated
      with poor relapse-free or overall survival, but resulted in a 41% postoperative
      irradiation rate. Further research is needed to establish the value of LVSI in
      postoperative radiotherapy decision making.

PMID- 11240768
TI  - Human papillomavirus in malignant cervical lesions in Surinam, a high-risk
      country, compared to the Netherlands, a low-risk country.
AB  - In various countries epidemiologic studies show an association between human
      papillomavirus (HPV) and cancer of the uterine cervix. We determined the presence
      of HPV and the distribution of the different HPV genotypes in cervical carcinomas
      from Surinam, a high-incidence country. The results were compared to the
      Netherlands where the incidence is five times lower. One hundred thirty cervical
      carcinomas from patients in Surinam were randomly selected and compared to an
      unselected group of 128 cervical carcinomas from caucasoid Dutch patients.
      Presence of HPV and distribution of HPV genotypes was determined in DNA extracted
      from paraffin-embedded specimens by polymerase chain reaction and sequence
      analysis. HPV DNA was detected in 82% of the Surinamese cervical cancer patients
      and in 87% of the Dutch patients. Thirteen different HPV genotypes were detected
      in the Surinamese group, and nine different HPV genotypes were detected in the
      Dutch group. Among the HPV-positive samples, HPV 16 was present in 68% in the
      Netherlands compared to only 49% in Surinam, where less common genotypes such as
      HPV 35, 45, and 58 were more prevalent. The results show a strong association
      between HPV and cervical cancer in both groups. However, the observed significant
      variation in distribution of the genotypes in the two populations with a large
      difference in cervical carcinoma incidence is important to the general
      understanding of the etiology of cervical cancer and to the development of HPV
      vaccination strategies.

PMID- 11240769
TI  - Surgically-treated early cervical cancer: Prognostic factors and the significance
      of depth of tumor invasion.
AB  - The objectives of this study were to scrutinize surgical features and analyze
      local tumor parameters of early cervical cancer to identify patients at-risk for
      recurrent disease. Three hundred eight patients who underwent radical
      hysterectomy and pelvic lymphadenectomy between 1984 and 1997 were studied
      retrospectively. All radical hysterectomies were performed in a referral oncology
      center, and treatment policies and operating staff were the same during the study
      period. Operating time gradually decreased significantly during the study period
      from an average of 270 min to an average of 187 min (P < 0.0001), and blood loss
      during surgery also decreased continually from 1515 ml to 1071 ml (P < 0.0001).
      Postoperative radiation treatment was given to 119 patients (40%). The overall
      five-year survival rate was 83%, 91% for those with negative, and 53% for those
      with positive pelvic nodes. Univariate analysis showed that lymph node status,
      parametrial involvement, status of the surgical margins, capillary lymphatic
      space involvement, tumor size and depth of invasion were all significantly
      related to the occurrence of recurrent disease. Multivariate analysis revealed
      that lymph node involvement (hazard ratio 4.4), parametrial involvement, tumor
      size and depth of invasion were independent factors of prognostic significance
      for disease-free survival. It was concluded that the local control of cervical
      tumors infiltrating > 10 mm (hazard ratio 5.1) might be improved by adjuvant
      radiotherapy, even in the absence of lymph node metastasis, parametrial
      involvement or affected surgical margins.

PMID- 11240770
TI  - Lack of association between HLA DQB1 alleles with HPV infection and histology
      findings in cervical cancer in Australian women.
AB  - The association of human leukocyte antigen (HLA) types with cervical cancer and
      human papillomavirus (HPV) infection is controversial. In this study we examined
      186 Australian women who had biopsy-confirmed cervical cancer and detected HLA
      DQB1 alleles and HPV DNA, using the polymerase chain reaction (PCR) amplification
      and sequence specific oligonucleotides probe (SSOP) hybridization methods. We
      analyzed the frequencies of 11 DQB1 alleles according to HPV DNA status (HPV
      positivity and HPV genotyping) and histology (tumor type, staging, grades,
      lymphocyte infiltration and nodal status). No significant differences among these
      11 HLA DQB1 alleles were found with respect to HPV status and histology.

PMID- 11240771
TI  - Cisplatin, radiation, and amifostine in carcinoma of the uterine cervix.
AB  - A pilot, open, comparative study was performed on patients with locally advanced
      cervical cancer to investigate the efficacy and safety of amifostine. Twenty
      patients with a histologic diagnosis of squamous cervical cancer were treated
      with radiotherapy and randomized in two groups. Group A received cisplatin at 20
      mg/m2 for five days in two cycles during intracavitary radiotherapy and 100 mg/m2
      x 2 cycles during external radiotherapy, and amifostine 825 mg/m2 15 min before
      the cisplatin infusion. Patients in group B received cisplatin in the same doses
      without amifostine. All patients had complete responses during a median follow-up
      of 20 months. Grade three neutropenia was present in two patients in group A and
      in four of the control group, P = 0.31; grade 2 neurologic toxicity was seen in
      four patients in group B and in one of the patients in group A, P = 0.15. One
      patient needed temporary interruption of amifostine due to hypotension. Eight of
      10 patients in group A developed hypocalcemia during the treatment with
      amifostine. Our findings indicate that amifostine was well tolerated. In this
      series a mild neurologic and hematologic protection was found in patients that
      received amifostine, although this was not statistically significant. No
      differences in disease-free survival response and overall survival was seen
      between the two groups.

PMID- 11240772
TI  - Prognostic factors in ovarian carcinoma in complete histologic remission at
      second-look surgery.
AB  - Prognosis of ovarian carcinoma in complete histologic remission (CHR) at second
      look surgery is still controversial. In a series of 83 patients in CHR we studied
      retrospectively several prognostic factors (age, stage, histologic grade,
      histologic type, initial residual disease after surgery, CA 125 normalization
      period) to determine which patients present a high risk of relapsing after CHR
      and could be included in therapeutic protocols for consolidation treatment.
      Univariate analysis showed that the combination of CA 125 normalization < 8 weeks
      with absence of macroscopic tumoral residue after initial surgery permits the
      definition of a group with a very good prognosis, while for patients with CA 125
      normalization period > 8 weeks and an initial macroscopic residual tumor, the
      prognosis is relatively poor (progression-free survival 100% vs. 47%, at 2 years
      P < 0.05). Using the Cox multivariate analysis, only the initial tumoral residue
      is of prognostic significance for progression-free survival; there is no
      prognostic significance for overall survival. The therapeutic strategy for
      ovarian cancer may be improved for patients in CHR after second-look surgery by
      determining those at high risk, making it possible to confine consolidation
      treatment trials to such a group.

PMID- 11240773
TI  - Thermal artefact after diathermy loop excision and laser excision cone biopsy.
AB  - Whether or not thermal artefact precludes accurate histopathologic assessment of
      excision biopsies of the uterine cervix is currently controversial. Some authors
      state that margins cannot be assessed at all while others feel that the
      pathologist can 'see through' the artefact in the majority of cases. Over a 7
      month period, 164 patients had loop excision and 84 patients had laser cone
      biopsy. The zone of coagulation at the specimen periphery was measured and the
      adequacy of excision assessed. The average width for this zone of coagulation in
      diathermy loop was 0.32 mm and for laser cone biopsies was 0.31 mm. In 12% of the
      loop specimens the line of excision was compromised by dysplasia or its
      assessment was rendered uncertain by thermal artefact. This was far more common
      in fragmented specimens (20%) compared to those removed as a single specimen
      (6%). In this study, 40% of patients had fragmented loop specimens. Thus, in
      attempting to replace cone biopsy with loop excision, we are asking pathologists
      to reassemble a pathologic jigsaw, then look through the thermal artefact for a
      decision on margins. We believe that this fragmentation should preclude the use
      of loop excision for lesions which would previously have been managed by cone
      biopsy.

PMID- 11240774
TI  - Pathologic stage III endometrial cancer treated with adjuvant radiation therapy.
AB  - This study was undertaken to evaluate the outcome of pathologic stage III
      endometrial carcinoma treated with adjuvant radiation therapy (RT). A
      retrospective review was performed on 32 patients receiving adjuvant RT following
      abdominal hysterectomy for stage III endometrial carcinoma (19 IIIA, 2 IIIB, 11
      IIIC) between 1980 and 1996. Papillary-serous and clear cell adenocarcinomas were
      excluded. Pathologic nodal sampling was performed on 25 patients (78%). All
      patients received postoperative external beam RT to the pelvis and 25 of 32
      received an additional brachytherapy boost to the vaginal apex. Three patients
      with involved para-aortic nodes received extended field RT. Mean follow up was 70
      mos. Twenty-four patients remain disease-free at mean follow-up of 68 mos.
      Distant recurrence (DR) occurred in 7 patients at mean of 38 mo. Two local
      failures were associated with DR. Six patients died of disease after recurrence
      despite salvage systemic therapy. One patient developed isolated local failure
      (vaginal apex) and remains disease-free 37 mo after surgical/chemotherapeutic
      salvage. 5 of 8 (45%) stage IIIC patients developed recurrence vs. only 2 of 19
      (10%) stage IIIA cases. 2 of 3 patients treated with extended field RT for
      positive para-aortic nodal disease remain disease-free at 128 and 56 mo. Long
      term survival can be achieved in stage III endometrial carcinoma. Few patients
      with either adnexal metastases or positive cytology alone develop recurrence.
      However, patients with stage IIIC disease fare poorly with local therapy alone.

PMID- 11240776
TI  - Port site recurrences following laparoscopically managed early stage endometrial
      cancer.
AB  - Laparoscopic management of endometrial cancer, although gaining in acceptance,
      has been associated with recurrent disease at trocar insertion sites in advanced
      disease. We report on a patient with a port site recurrence in early stage
      endometrial cancer. An 84-year-old patient with cancer of the endometrium
      underwent a laparoscopic surgical staging, vaginal hysterectomy, and adjunct
      radiation treatment. The final surgical pathology was grade 3, stage IC
      endometrioid adenocarcinoma. Seven months post-treatment, she presented with
      bilateral port site recurrences in the lower abdominal wall. Trocar port site
      recurrence in gynecologic cancer patients may be enhanced by laparoscopic
      management and are not limited only to patients with advanced disease.

PMID- 11240775
TI  - Adjuvant high-dose rate brachytherapy with or without external beam radiotherapy
      post-hysterectomy for endometrial cancer.
AB  - The purpose of this study was to evaluate patient selection, local control,
      survival and late toxicity of posthysterectomy adjuvant radiotherapy and compare
      adjuvant external beam therapy and high-dose rate (HDR) brachytherapy versus HDR
      brachytherapy alone. A retrospective analysis was performed on a series of 225
      patients with endometrial cancer treated with external beam radiotherapy and HDR
      brachytherapy or HDR brachytherapy alone posthysterectomy from 1985 to June 1993.
      Of these 225 patients, 82 received external beam radiotherapy and brachytherapy
      and 143 received brachytherapy alone. The HDR fraction size was 8.5 Gy prescribed
      to the mucosal surface; two fractions were given after external beam and four
      fractions if brachytherapy alone was used. The median follow-up was 6.9 years.
      The patients who received combined external beam and brachytherapy had higher
      stage and grade tumors. The survival outcome was similar for either group when
      matched for stage. Overall relapse-free survival at five years was 96% and 81%,
      respectively for brachytherapy alone and combined adjuvant therapy. Pelvic
      recurrence was seen in 2.7% of patients. Toxicity was more common with external
      beam radiotherapy and brachytherapy compared to brachytherapy alone (45.1% vs
      23.1%, P = 0.003). However, moderate or severe toxicity was rare but again was
      more common in the combined radiotherapy group (8.5% vs 2.1%, P = 0.04). There
      was a non-significant trend to increased toxicity after lymphadenectomy and
      external beam radiotherapy compared with patients who did not have a staging
      lymphadenectomy prior to external beam radiotherapy (62% vs 38%, P = 0.16).
      Adjuvant radiotherapy can be individualized and be based upon the information
      provided by the pathological specimens, which excluded external beam radiotherapy
      if a lymphadenectomy was performed and there was no evidence of extra-uterine
      disease. This study found more toxicity associated with adjuvant radiotherapy
      compared with other studies, but this may reflect different reporting criteria.
      There was more toxicity related to external beam radiotherapy and brachytherapy
      compared to brachytherapy alone. The two HDR brachytherapy protocols used in this
      series appear effective and safe.

PMID- 11240777
TI  - First reported case of endometrial carcinoma in association with HIV infection.
AB  - Endometrial adenocarcinoma is the most common gynecologic cancer in developed
      countries, although it has never before been documented in a female infected with
      human immunodeficiency virus (HIV). By contrast, cervical carcinoma is well
      described in association with HIV infection and in 1993 was added to the AIDS
      case definition. We present the unique case of a 38-year-old HIV-infected female
      with endometrial carcinoma, who became rapidly disseminated following her initial
      surgery. Although HIV is unlikely to have an etiologic role in endometrial
      carcinoma, it is conceivable that immunosuppression contributed to an accelerated
      course of her malignancy.

PMID- 11240778
TI  - Regarding management of VIN 3.

PMID- 11240779
TI  - The use of vaccines in treating cervical cancer: present status and future
      prospects.
AB  - HPV types are carcinogenic agents in cervical cancer. This view is supported by
      epidemiological and biological evidence. The oncogenic products and capsid
      proteins of high risk HPV types are potential targets against which effective
      immunity may be generated by vaccination. Both therapeutic and prophlylactic
      immunisation are potential strategies to deal with the widespread problem of HPV
      infection and possibly established cervical neoplasia. Clinical trials are now
      underway to evaluate candidate vaccines.

PMID- 11240780
TI  - Cervical tumor characterization by transvaginal color flow Doppler ultrasound.
AB  - The aim of the study was to investigate the blood flow characteristics of benign
      cervical lesions and invasive cervical tumors and to determine if invasive
      cervical tumors can be predicted by transvaginal sonography (TVS) and color flow
      Doppler (CFD). The study design incorporated an open prospective collection of
      data from patients attending the Women's Cancer Center, University of Minnesota
      and the Sydney Women's Cancer Center. Inclusion criteria included patients with
      known benign or malignant cervical pathology. The study group of 66 patients
      comprised 32 patients with invasive cervical cancer and 34 patients with benign
      cervical lesions. Benign cervixes were significantly more likely to have absent
      or normal flow whereas malignant lesions were significantly more likely to have
      abnormal or increased flow (P < 0.0001). No differences in the uterine or
      intratumor systolic, diastolic, or mean velocity were found between the two
      groups. A reduction in the uterine artery pulsatility index (PI) and resistance
      index (RI) from 1.84 to 1.55 and 0.73 to 0.71, respectively, and also in the
      intracervical PI from 1.5 to 1.1, in the benign compared to invasive group was
      found, none of which reached statistical significance. However the intracervical
      RI was statistically lower (0.62) in malignant tumors compared to patients with
      benign lesions (0.71) (P = 0.03). The effect of menopause on blood flow
      characteristics was variable and overall not significant. While the uterine
      artery systolic velocity was significantly higher in premenopausal women, no such
      effect was found for the diastolic or mean velocity or the PI and RI. In
      postmenopausal women, the intratumor PI and RI were higher compared to
      premenopausal women. In conclusion, transvaginal CFD analysis of the uterine
      arterial or intratumor bed does not appear to be beneficial in attempting to
      distinguish benign from malignant cervical tumors.

PMID- 11240781
TI  - Surgery followed by radiotherapy in endometrial cancer: analysis of survival and
      patterns of failure.
AB  - We performed a retrospective evaluation of survival and patterns of failure in
      317 consecutive endometrial cancer patients treated between 1974 and 1991 with
      surgery and adjuvant radiotherapy. Two hundred and forty seven patients (78%) had
      FIGO stage I disease, 30 (9%) - stage II, 35 (11%) - stage III and 5 (2%) - stage
      IV. Both low dose rate brachytherapy (BRT) and external beam radiation (EBRT)
      were applied in 247 patients (78%), only BRT in 49 (15%), and only EBRT in 21
      (7%). Median follow-up was 7.3 years. Five-year overall survival was 75%, and
      five-year disease free survival was 81%. Both overall and disease free survival
      rates were correlated with stage (P = 0.001 and P = 0.000, respectively).
      Recurrence occurred in 70 patients (22%): 11 (3.5%) in the pelvis, 51 (16%)
      outside the pelvis and 6 (2%) both in- and outside the pelvis. Independent risk
      factors for local recurrence included older age (P = 0.03) and variant histologic
      subtypes (P = 0.039), whereas independent risk factors for distant spread were
      stage (P = 0.000) and older age (P = 0.011). Normalized Total Dose (the sum of
      EBRT and BRT doses, based on linear-quadratic equation), type of radiotherapy
      regimen, overall radiotherapy time and surgery-to-radiotherapy interval did not
      correlate with the risk of relapse. Severe early and late radiotherapy
      complications were observed in 21 (7%) and 35 patients (11%), respectively. In
      view of the relatively low risk of exclusive pelvic recurrences and the high rate
      of severe late radiotherapy complications, indications for postoperative
      radiotherapy and its scheme should be verified. A relatively high rate of
      extrapelvic recurrences calls for effective systemic adjuvants to surgery.
      Further definition of high risk patients is warranted in order to tailor
      postoperative therapy to the prognostic factors and to increase the therapeutic
      index of management of endometrial cancer.

PMID- 11240782
TI  - Radical hysterectomy for recurrent or persistent cervical cancer following
      radiation therapy.
AB  - The objective of this paper was to determine the role of radical hysterectomy in
      persistent or recurrent cervical cancer after primary radiation therapy. Between
      1982 and 1995, 34 patients underwent radical hysterectomy for persistent (n = 15)
      or recurrent (n = 19) cervical cancer after primary radiotherapy. Univariate
      analysis using log-rank comparison of survival curves was conducted to identify
      clinical and pathologic factors predictive of survival. The median tumor size at
      the time of recurrence or persistence was 3.2 cm (range 1-6 cm). 24 patients
      (70%) had recurrence limited to the uterine cervix; four (12%) had vaginal
      involvement and six (18%) had early parametrial involvement. No treatment-related
      deaths were observed. Eighteen major complications (grade III-IV) occurred in 15
      cases (44%); 5 patients experienced a fistula. Mean follow-up time was 81 months
      (range 33-192 months). Recurrent disease was documented in 20 patients (59%), and
      median time to recurrence was 37 months (range 4-56 months). Fifteen patients
      (44%) are alive without evidence of disease at a median survival of 81 months
      (range 33-192), and 18 patients (53%) died of disease with a median survival of
      22 months (range 7-106). One patient died of intercurrent disease. Actuarial 5
      year survival rate for the whole group is 49%. Patients with FIGO stage IB-IIA at
      primary diagnosis, no clinical parametrial involvement, and small (</= 4 cm)
      tumor diameter at the time of recurrence show a good prognosis (11/17 alive NED)
      compared to patients who do not fit the above mentioned criteria (4/17 NED, P =
      0.01). We conclude that radical hysterectomy can be offered as an alternative
      procedure to exenteration only in highly selected patients.

PMID- 11240783
TI  - Involvement of internal genitalia in female patients undergoing radical
      cystectomy for bladder cancer: a clinicopathologic study of 37 cases.
AB  - Radical cystectomy for invasive bladder cancer in female patients implies
      anterior pelvic exenteration. The necessity for routine removal of all internal
      female genitalia has not, as yet, been investigated. The present study was
      conducted to investigate the involvement of internal genitalia in these patients.
      Cystectomy specimens from 37 consecutive female patients with bladder cancer were
      examined for internal genitalia and urethral involvement. Clinical data were
      retrospectively collected from hospital charts. Thirty-four patients were
      available for postoperative follow-up. Of the 37 cases, 30 were transitional cell
      carcinoma (TCC), 4 squamous cell carcinoma, 1 adenocarcinoma, and 2
      undifferentiated carcinoma. Uterine involvement was observed in only 1 case: TCC,
      stage D1, grade IV. All patients had normal ovaries and a normal vagina
      regardless of tumor site or stage; however, late ovarian and vaginal recurrences
      developed in one patient, in whom one ovary had been preserved. Sixteen percent
      of the patients had urethral involvement. We conclude that synchronous or
      metachronous involvement of female internal genitalia in bladder cancer is
      uncommon. Preservation of ovaries and vagina in young patients undergoing radical
      cystectomy may be considered under strict criteria.

PMID- 11240784
TI  - Radical hysterectomy for cervical cancer: hysterectomy before pelvic
      lymphadenectomy or vice versa?
AB  - The technique for radical abdominal hysterectomy (RAH) and lymphadenectomy (LND)
      for patients with cervical cancer has been well described. Whether RAH should be
      performed before or after pelvic lymph node dissection (PLND) is a controversial
      issue. This study compared the two procedures performed at the same institution.
      Patients treated with type III RAH for cervical cancer stage IB-IIA at our
      institution between 1987 and 1995 were included in this study. Only patients who
      underwent para-aortic lymph node dissection (PALND) first, followed by PLND and
      then RAH (Group A) or RAH and then PLND (Group B) were included. Clinical and
      surgical information including intraoperative and postoperative complications was
      collected. Operative reports were used to identify the patients who had RAH
      performed before PLND or vice versa. Data analysis was obtained using unpaired t
      test with significance set at P < 0.05. Complete information was obtained for 314
      patients. The results of Group A (157 patients) and Group B (157 patients) were
      as follows: mean age = 45.3 and 44.8 (P = 0.73); mean weight = 149 and 149 lb.;
      mean length of stay = 10 and 8 days (P < 0.0001); mean operative time = 230 and
      172 mins (P = 0.004); mean estimated blood loss (EBL) = 1,238 and 1098 cc (P =
      0.21); mean number of PALN removed = 7 and 6 (P = 0.06); mean number of PLN
      removed = 28 and 26 (P = 0.24). No statistical difference in major intraoperative
      and postoperative complications was observed. The most common complication was
      postoperative fever (53/157 in Group A and 49/157 in Group B). Radical
      hysterectomy can be safely performed either before or after PLND. The number of
      pelvic lymph nodes removed, as well as the EBL and the intraoperative
      complications are similar and are not affected by the operative time. The surgeon
      should decide the sequence of the procedures accordingly to his/her personal
      preference.

PMID- 11240785
TI  - Malignant mixed mullerian tumors of the ovary: histopathologic and clinical
      review of 36 cases.
AB  - Among 2,895 malignant ovarian tumor cases referred to Radiumhemmet, Stockholm
      from 1975 through 1995, 36 were certified to be malignant mixed mullerian tumors.
      The overall prognosis was poor with only 18% five-year actuarial survival (median
      survival 16.6 months). Five patients are still surviving after 75, 68, 117, 121,
      and 168 months, respectively. Fifteen women treated with melphelan, doxorubicin
      (adriamycin) and cisplatin (MAP) had a five-year actuarial survival of 33.3% and
      a median survival of 19.8 months. In a multivariate analysis taking into account
      stage, age, radiation, type of chemotherapy, histopathologic type and
      completeness of surgery, the most important predictors for survival were stage
      (stages I-II vs stages III-IV, P < 0.05), histopathologic type (homologous vs
      heterologous, P < 0.05), and type of chemotherapy (MAP or CAP vs other types, P <
      0.05). We concluded that homologous tumor and chemotherapy containing cisplatin,
      doxorubicin, and melphalan, as well as early stage of the tumor, provided the
      optimal survival rate.

PMID- 11240786
TI  - Markov optical texture parameters as prognostic indicators in ovarian carcinoma.
AB  - Texture is a descriptive property of a surface describing the morphometric
      heterogeneity of complex structures. Computer aided image analysis allows optical
      texture measurement and analysis of gray-scale images. The authors, utilizing
      image analysis, prospectively studied Markov nuclear texture features to
      determine their relevance as prognostic indicators of survival in patients with
      epithelial ovarian carcinoma. Ninety-nine consecutive patients with ovarian
      cancer, treated initially with surgery were evaluated for their length of
      survival, level of cytoreduction, FIGO stage, grade, histology, and DNA index, as
      well as 20 Markov texture features. Markov nuclear texture features were
      quantified using image analysis. Mean follow-up for the study population was 64
      months (median 59) with a range from 51 to 89 months. Five optical texture
      features showed significant correlation with length of survival. Difference
      entropy (P = 0.033) and information measure A (P = 0.041) were both indirectly
      correlated with survival while information measure B (P = 0.030), correlation
      coefficient (P = 0.045), and the maximum correlation coefficient (P = 0.041) were
      directly correlated. Only sum entropy (P = 0.035), FIGO stage (P = 0.0031), and
      level of cytoreduction (P < 0.0001) were independent predictors of survival in
      this population. Optical texture can be quantified by image analysis. Utilizing
      multivariate analysis, the Markov texture feature, sum entropy, was demonstrated
      to be an independent prognostic indicator of survival in patients with epithelial
      ovarian cancer. FIGO stage and optimal cytoreduction also were independent
      prognostic indicators of survival.

PMID- 11240787
TI  - Lymphadenectomy in high risk endometrial carcinoma stage I and II: no more
      morbidity and no need for external pelvic radiation.
AB  - The objectives of this retrospective study were to analyze the morbidity of
      surgical staging and to evaluate the omission of external radiotherapy in high
      risk patients with stage I and II endometrial carcinoma when the lymph nodes were
      negative. From 1988 to 1996, 63 of 117 patients underwent a pelvic and periaortic
      lymphadenectomy. The decision to perform lymphadenectomy was influenced by
      patient general health. Patients with lymphadenectomy had a better physical
      status (P < 0.0001). Lymphadenectomy increased mean operative time (P < 0.0001)
      and blood loss (P < 0.01), but there was no increase in postoperative
      complications. At a median follow-up of 54 months, there was one cuff recurrence
      in 56 patients. Nineteen high-risk patients without external pelvic radiation had
      the same disease-free survival rate as 37 low-risk patients (P = 0.1). In the
      group without lymphadenectomy, the disease-free survival for 18 high-risk
      patients and 32 low-risk patients was similar (P = 0.21). Surgical staging in
      properly selected patients does not increase postoperative complications and
      brachytherapy without external radiotherapy is associated with excellent disease
      free survival when the lymph nodes are negative.

PMID- 11240788
TI  - Atypical squamous cells of undetermined significance (ASCUS): clinical
      cytological significance.
AB  - The objective of this paper is to compare histologic results of microbiopsies
      and/or endocervical curettage obtained following the older cytological "atypical"
      diagnosis and the newer Bethesda ASCUS terminology. We reviewed a series of
      atypical smears (n = 245) from December 1991 to February 1995 and ASCUS cases (n
      = 120) from March 1995 to May 1996, when some atypias were renamed ASCUS
      according to the Bethesda classification. These patients were examined by
      colposcopy for cervical lesion and clinical evaluation. Menopausal women were
      underrepresented in atypical smears (n = 21/245, 8.6%) in comparison with ASCUS
      (n = 29/120, 24.2%, P = 0.001). Since, no low or high grade squamous
      intraepithelial lesion (L/HSIL) was ever found in the >/= 50 years group, we
      reviewed only patients under 50 years. Atypical smears resulted in 61/224 (27.2%)
      positive biopsies of which 47 (21%) were LSIL and 14 (6.2%) were HSIL; ASCUS
      smears yielded 17/91 (18.7%) positive pathology diagnoses with 13 (14.3%) LSIL
      and 4 (4.4%) HSIL. Endocervical curettage positivity (ECC) was at 6/109 (5.5%)
      for atypias, and 1/53 (1.9%) for ASCUS. Cervical biopsies in ASCUS smears show a
      tendency to a lower histologic positivity rate, in comparison with atypical
      cytology. Persistent ASCUS smears should be evaluated by colposcopy, and
      thereafter at 6-month intervals. The exact meaning of ASCUS, in spite of a 17.5%
      CIN rate, remains unknown, but constitutes a high-risk group.

PMID- 11240789
TI  - Adjuvant high-dose chemotherapy supported by peripheral blood stem cell
      transplantation for high-risk cervical carcinoma.
AB  - Cervical carcinoma is a common disease for which the prognosis has not been
      substantially improved with standard locoregional treatments. Three stage IB
      patients with untreated cervical carcinoma were treated with high-dose
      chemotherapy and refrigerated peripheral blood stem cell support using the ICE
      program (Ifosfamide 10 g/m2 plus mesna at 100% of the ifosfamide dose;
      Carboplatin at 1.5 g/m2 and Etoposide 2.1 g/m2). Patients received the treatment
      in an adjuvant setting after radical hysterectomy with pelvic lymph-node
      dissection and postoperative cisplatin-based standard-dose chemotherapy. All
      patients underwent postoperative radiotherapy. The treatment was well-tolerated,
      all patients had rapid hematologic recovery, and the most frequent complications
      were grade 3 mucositis and neutropenic fever. The three patients are disease-free
      at 58, 60, and 63 months of follow-up. Our results show that adjuvant high-dose
      chemotherapy could be effective to reduce the likelihood of relapse in high-risk
      patients. High-dose chemotherapy deserves a formal evaluation in high-risk
      cervical cancer.

PMID- 11240790
TI  - Evaluation of lymph nodes in squamous cell carcinoma of the cervix: touch imprint
      cytology versus frozen section histology.
AB  - Metastatic involvement of pelvic lymph nodes (LNs) is the most important negative
      predictor of survival in early stage cervical cancer. Because the presence of
      nodal metastases precludes the continuance of any radical surgical procedure, an
      extraperitoneal LN dissection is performed and LNs are sent for frozen section
      (FS). As the time for routine FS is about 15 minutes per LN, the use of a faster
      method, cytology by touch imprint (TI), was investigated. A prospective study was
      performed to determine the feasibility of TI technique vs. FS. Three hundred
      eighteen pelvic and para-aortic LNs from 32 patients with cervical cancer of
      stage I-IV were bisected and submitted for FS after TI had been prepared. Twenty
      nine nodes (9.1%) revealed metastatic squamous cell carcinoma (SCC) by frozen
      section histology. Twenty-six of these were diagnosed by TI and confirmed
      histologically. Reasons for the 3 false negatives included inadequate preparation
      or misinterpretation of the TI. Permanent histology always agreed with the frozen
      section result. Cytologic evaluation of pelvic LNs for SCC at the time of
      intraoperative consultation had a sensitivity and specificity of 90% and 100%,
      respectively. Touch imprints may provide a sensitive, specific, and time
      efficient method to diagnose nodal metastases in cervical SCC.

PMID- 11240791
TI  - Prognostic significance of cyclin D1 gene (CCND1) polymorphism in epithelial
      ovarian cancer.
AB  - We have investigated the influence of CCND1 genotype on clinical outcome in 138
      women with epithelial ovarian cancer. CCND1 genotypes were identified from
      peripheral blood DNA by polymerase chain reaction restriction fragment length
      polymorphism (PCR-RFLP) analysis. Patient CCND1 genotypes were compared with
      clinical details including FIGO tumor stage, residual tumor volume, tumor
      histology and differentiation, response to chemotherapy, progression free
      interval, and survival. We observed no association between patient CCND1
      genotypes and tumor characteristics or response to chemotherapy. There was no
      significant difference in overall survival and progression free interval (PFI)
      among women with different CCND1 genotypes. However, analysis of data from
      patients who responded to postoperative chemotherapy revealed that women with
      CCND1 AA genotype were associated with early disease progression (P = 0.020, HR
      4.58, 95% CI 1.27-16.48) and reduced survival (P = 0.026, HR 4.48, 95% CI 1.19
      16.79) compared with those with CCND1 AG and GG genotypes. These data show that
      CCND1 genotype does not influence overall prognosis in a cohort of epithelial
      ovarian cancer patients, however, it is associated with disease progression in a
      subgroup of patients following initial response to chemotherapy.

PMID- 11240792
TI  - Early clitoral carcinoma successfully treated by radiotherapy and bilateral
      inguinal lymphadenectomy.
AB  - A 42 year-old female presented with an early stage IB squamous cell carcinoma
      involving the clitoris. She was treated with radical radiotherapy to the clitoris
      and peri-clitoral region and bilateral inguinal lymphadenectomy. The treatment
      was well tolerated. The vulvar appearance, sensation and orgasmic function have
      not been impaired. There has been no recurrence during five years of follow-up.
      Radiotherapy and bilateral inguinal lymphadenectomy are an effective therapeutic
      option in early stage IB carcinoma involving the clitoris in sexually active
      females.

PMID- 11240793
TI  - Imaging of ovarian carcinoma.

PMID- 11240794
TI  - Failure of megestrol acetate to reverse tamoxifen induced endometrial neoplasia:
      two case reports.
AB  - Tamoxifen's agonist effect on the endometrium has been associated with an
      increased incidence of endometrial carcinoma. It has been suggested that this
      agonist effect may be averted by the concomitant use of a progestational agent.
      We report two patients with breast cancer receiving tamoxifen who developed
      endometrial carcinoma and atypical endometrial hyperplasia, respectively. In one
      patient, this occurred despite the use of concomitant megestrol acetate. In the
      other patient, tamoxifen-associated endometrial hyperplasia persisted and
      progressed despite cessation of tamoxifen and initiation of megestrol acetate
      therapy. These cases may have implications for strategies to avert tamoxifen
      induced endometrial neoplasia.

PMID- 11240795
TI  - Efficacy of intraperitoneal adenovirus-mediated p53 gene therapy in ovarian
      cancer.
AB  - The purpose of this study was to determine the efficacy of adenovirus-based p53
      gene therapy in the treatment of ovarian cancer using an intraperitoneal
      microscopic tumor animal model system. Adenovirus-mediated wild-type p53 gene was
      introduced into the NIH:OVCAR-3 human ovarian cancer cell line in vitro and in
      vivo. In order to study microscopic intraperitoneal tumor, athymic nude mice were
      inoculated intraperitoneally (i.p.) with 1 x 107 OVCAR-3 cells and observed for
      tumor growth. Three days after inoculation with OVCAR-3 cells, the mice were
      divided into 3 treatment groups. One group received three daily i.p. injections
      of 1 x 108 pfu Ad-CMV-p53, a second group received three daily i.p. injection of
      1 x 108 pfu of the control adenovirus construct expressing beta galactosidase (Ad
      CMV-betagal) and a third group received three daily i.p. injections of normal
      saline. Adenovirus-mediated introduction of the wild-type p53 gene in the ovarian
      cancer cell line resulted in transient high levels of p53 protein for 24-48 h.
      Cell cycle analysis revealed G1 arrest, as well as the appearance of apoptosis.
      In vitro cell growth assays showed growth inhibition of cancer cells infected
      with Ad-CMV-p53 compared to cells infected with Ad-CMV-betagal or normal saline.
      There was a significant increase in survival in the Ad-CMV-p53 adenovirus treated
      animals compared to the PBS treated animals (P = 0.004). Likewise, the survival
      in Ad-CMV-p53 treated mice was also significantly greater than mice treated with
      Ad-CMV-betagal (P < 0.0001). These results demonstrated that Ad-CMV-p53 treatment
      is effective in inhibiting tumor growth and prolonging survival in this
      microscopic cancer xenograft model. The results of this study constitute a step
      in translating promising in vitro and in vivo data from an adenovirus-based gene
      therapeutic model system into practical and scientifically based human cancer
      therapeutic trials.

PMID- 11240796
TI  - A phase II study of biweekly administration of paclitaxel in patients with
      recurrent epithelial ovarian cancer.
AB  - The purpose of this study was to assess the efficacy and toxicity of single agent
      paclitaxel administered biweekly to patients with relapse of epithelial ovarian
      cancer previously treated with platinum-based regimen. Forty patients received an
      initial paclitaxel dose of 134 mg/m2 administered intravenously over three hours
      every two weeks. 283 cycles were given. All 40 patients were evaluable for
      toxicity, which mainly consisted of granulocytopenia, myalgia/arthralgia, and
      peripheral neuropathy. Two patients developed severe hypersensitivity reactions.
      Dose escalation was possible by one level in 11 patients and by two levels in 12
      patients, dose reductions were not necessary. Thirty-five patients were evaluated
      for response. Five obtained complete response (14%), eight obtained partial
      response (23%), and nine had stable disease (26%), while 11 patients showed
      progression (31%). The overall response rate was 37% (95% confidence interval 22
      57%). The median duration of responses (complete and partial) was six months.
      Overall median time to progression and overall median survival for eligible
      patients (n = 35) was 4.3 months and 11 months, respectively. We conclude that
      biweekly administration of paclitaxel in recurrent epithelial ovarian carcinoma
      was active with manageable toxicity.

PMID- 11240797
TI  - The distribution of alpha inhibin and alpha glutathione S-transferase (delta4-5
      isomerase) in the ovaries of patients with endometrial carcinoma.
AB  - Estrogen is to thought to play a role in the pathogenesis of low grade but not
      high grade endometrial carcinomas. The dominant circulating estrogen in post
      menopausal women is estrone which is formed by aromatization of androstenedione.
      delta4-5 isomerase, active in the conversion of dehydroepiandrosterone to
      androstenedione, may be demonstrated immunohistochemically by the antibody to
      alpha glutathione S-transferase (alphaGST). Inhibin, normally acting to suppress
      FSH secretion, also has an LH-dependent paracrine stimulatory effect on ovarian
      stromal cells to produce androstenedione. The purpose of this study was to
      compare the distributions of alphaGST and alpha inhibin in the ovaries of
      patients with low grade and high grade endometrial carcinomas. The results show a
      statistically significant increase in intracytoplasmic alphaGST staining in
      patients with low grade endometrioid adenocarcinomas compared to high grade
      carcinomas. There was also a statistically significant correlation between the
      distribution of alphaGST and alpha inhibin. These findings lend some support to
      the hypothesis that estrogen plays a role in the pathogenesis of low grade
      carcinomas; that the increase in estrone is partly due to increased production of
      androstenedione by the ovary and that this increased production could be the
      consequence of increased inhibin paracrine activity.

PMID- 11240798
TI  - Endometrial cancer: accuracy of the finding of a well differentiated tumor at
      dilatation and curettage compared to the findings at subsequent hysterectomy.
AB  - The objective of this study was to examine the accuracy of the finding of a
      histologically well differentiated endometrial carcinoma at dilatation and
      curettage (D & C) prior to hysterectomy. A retrospective multicentric chart
      review of 137 endometrial cancer patients was conducted, including all patients
      in whom a well differentiated endometrial carcinoma had been diagnosed by D & C.
      Histopathologic grading as determined by D & C was compared with the grading
      established at the final histologic examination after hysterectomy. Seventy-eight
      percent of all cases in which a well differentiated tumor was diagnosed with D &
      C were confirmed as well differentiated endometrial carcinomas, whereas 20.4% had
      to be upgraded as moderately differentiated tumors after evaluation of the
      hysterectomy specimen. In one case in which a uterine adenocarcinoma was
      diagnosed by D & C, a well differentiated adenocarcinoma was found to be combined
      with a carcinosarcoma in the hysterectomy specimen. In order to avoid false
      findings of a well differentiated tumor, the histologic grade should be confirmed
      by intraoperative frozen section examination. This is especially important in
      cases in which surgical staging was not planned initially.

PMID- 11240799
TI  - Sexual outcomes following treatment for early stage gynecological cancer: a
      prospective multicenter study.
AB  - Data are presented of a prospective, longitudinal study on the impact of early
      stage gynecological cancer on sexuality. Women with a partner (n = 58) completed
      self-report questionnaires following diagnosis but prior to treatment and then at
      6 and 12 months post-treatment. A single assessment was also obtained from a
      healthy comparison group (n = 103). Pre-treatment cancer patients reported fewer
      and less trouble with sexual problems compared to healthy controls. Neither
      sexual satisfaction nor sexual activity changed from pre- to post-treatment and
      was comparable to that of healthy controls. Post-treatment, relatively minor
      sexual difficulties were shown; a notable difficulty for cancer patients
      concerned lubrication. At 12 months post-treatment, the sexual functioning of
      cancer patients was comparable to healthy controls.

PMID- 11240800
TI  - Benefits and side effects of lateral ovarian transposition (LOT) performed during
      radical hysterectomy and pelvic lymphadenectomy for early stage cervical cancer.
AB  - Ovarian function and ovarian cyst formation after radical hysterectomy and pelvic
      lymphadenectomy with lateral ovarian transposition (LOT) have been
      retrospectively examined in 54 patients with early stage cervical cancer (FIGO IB
      or IIA) with a follow-up of 3-7 years. Patients were divided into two groups:
      those without adjuvant pelvic radiotherapy (36 patients) and those with adjuvant
      pelvic radiotherapy (18 patients). Ninety-one percent (33/36) of the patients
      without adjuvant pelvic radiotherapy and 66% (12/18) of the patients with
      adjuvant pelvic radiotherapy remained without evidence of recurrent disease. Of
      the 36 patients who did not receive adjuvant pelvic radiotherapy, only two
      patients became postmenopausal (5.5%). However, of the 18 patients who also
      received adjuvant pelvic radiotherapy, 5 became postmenopausal (28%). There was a
      tendency to become postmenopausal if the scatter radiation dose at the transposed
      ovaries was 300 cGy or more, but our series is too small to allow a definite
      conclusion. This scatter radiation dose did not depend on the distance the
      ovaries were placed from the linea innominata, because of the variation in the
      level of the cranial border of the radiation field. Three out of 54 patients
      (5.5%) developed symptomatic ovarian cysts, of which 2 required surgical
      intervention because of pain symptoms. Remarkably, in one of them cyst formation
      occurred 5 years after surgery. Of the 3 patients with symptomatic ovarian cysts
      this was the only patient who received adjuvant pelvic radiotherapy. From these
      data it can be concluded that LOT protects ovarian function in most patients
      undergoing radical hysterectomy and pelvic lymphadenectomy for early stage
      cervical cancer, even if they receive adjuvant pelvic radiotherapy, with an
      acceptable risk of development of symptomatic ovarian cysts.

PMID- 11240801
TI  - Combination of radiation therapy and interferon alpha-2b in patients with
      advanced cervical carcinoma: a pilot study.
AB  - Carcinoma of the uterine cervix is the most frequent malignancy in women in
      developing countries. Based on the possible synergistic effect of the combination
      of interferon and radiotherapy, a clinical trial was conducted in patients with
      advanced cervical cancer. The objective was to evaluate the efficacy and security
      of such a therapeutic approach. This prospective phase II trial was done at the
      Instituto Nacional de Cancerologia in Mexico City. The study included 17
      consecutive patients with previously untreated squamous cell cervical cancer,
      clinical stages III and IV, and tumor mean size of 9.7 cm. The patients received
      radiotherapy and interferon alpha-2b at a dose of 5 x 106 IU/m2 3 times a week
      for 6 weeks. Eleven (64%) complete responses were obtained among these patients.
      Long-term survival was observed in 4 patients (24%) who achieved complete
      response and are alive after 10 years of follow-up. Immediate toxicity was mild.
      Late toxicity included the development of proctitis in 13 patients, colostomy was
      performed in 3 (23%) of them. Our results indicate that the combination of
      radiotherapy and this cytokine is an active therapy for squamous cell carcinoma
      of the uterine cervix.

PMID- 11240802
TI  - Clinical and pathologic significance of microsatellite instability in endometrial
      cancer.
AB  - Microsatellite instability (MSI) is identified as electrophoretic shifts in
      allele sizes of microsatellite DNA sequences. It is characteristic of a subset of
      sporadic colorectal tumors as well as hereditary nonpolyposis colorectal cancer
      (HNPCC). The cells that display MSI are thought to be susceptible to increased
      mutability. MSI has been detected in a wide variety of human tumors, but the
      influence of this form of genetic instability on disease initiation and
      progression remains unclear. Using a polymerase chain reaction (PCR)-based method
      we screened 50 sporadic primary endometrial carcinomas to characterize the
      prevalence of MSI in these tumors and analyze the correlation of MSI with
      clinicopathologic parameters in this malignancy. Fifteen cases (30%) displayed
      low frequency of MSI (MSI-L) showing MSI at one locus in 5 loci examined. Two
      cases (4%) showed high frequency of MSI (MSI-H) having MSI at 2 or more loci.
      Taking MSI-L and MSI-H cases together as MSI-positive, statistical analysis of
      patient age, tumor grade, and stage failed to disclose significant differences or
      trends between cases with MSI-positive and MSI-negative (P > 0.05). No
      significant relationship was observed between patients with MSI and without MSI
      (P > 0.05), however, the MSI exhibited only in those cases without evidence of
      disease at the 24th month after treatment. The difference is statistically
      significant when compared with patients who are alive with disease or died of
      disease (P < 0.01). However, the overall survival curves were not statistically
      different. We conclude that MSI is present in a subgroup of endometrial cancer.

PMID- 11240803
TI  - Prevalence of cervical cancer and feasibility of screening in rural China: a
      pilot study for the Shanxi Province Cervical Cancer Screening Study.
AB  - For cervical cancer screening to be feasible in developing countries, it must be
      accurate, inexpensive, and easy to administer. We conducted a pilot study in
      rural Shanxi Province, People's Republic of China, to determine disease
      prevalence and study feasibility in preparation for a large-scale comparative
      trial of 6 screening tests. One-hundred and thirty-six nonpregnant women with no
      history of hysterectomy, pelvic radiation, or Papanicolaou tests were screened in
      a rural clinic. Ten percent of the women enrolled reported abnormal vaginal
      bleeding and 45% reported abnormal vaginal discharge. The tests were the
      Papanicolaou test (both conventional and ThinPrep), a self-administered swab test
      by Hybrid Capture II for high-risk human papillomavirus (HPV), a test for high
      risk HPV from residual PreservCyt medium, fluorescence spectroscopy, and visual
      inspection of the cervix by a clinician. All women also underwent colposcopy and
      biopsies as the reference standard. Biopsies showed 12 of 136 women had >/= high
      grade squamous intraepithelial lesions (HGSIL). Screening was completed in 5 half
      day sessions, the procedures went smoothly, and local cooperation was
      enthusiastic. Disease prevalence in Xiangyuan and Yangcheng Counties, Shanxi
      Province, can be estimated at 8.8% (95% CI, 4.5% to 15.0%). Screening 1000-2000
      patients would be sufficient to detect a 10% difference in accuracy between
      diagnostic tests. The proposed large-scale trial is feasible.

PMID- 11240804
TI  - Evaluation of the Pfannenstiel incision for radical abdominal hysterectomy with
      pelvic and para-aortic lymphadenectomy.
AB  - Radical abdominal hysterectomy with pelvic and para-aortic lymphadenectomy (RAH/P
      + PAL) has classically been described through a low midline vertical incision.
      Transverse incisions have been used with good results for various pelvic surgical
      procedures. Hesitancy has been encountered when utilizing these transverse
      incisions in gynecologic oncology patients. In most studies, muscle-splitting
      transverse incisions seem to be of equal efficacy as midline vertical incisions
      in regards to surgical exposure and clinicopathologic data obtained and are known
      to be superior in cosmesis and postoperative morbidity. A retrospective chart
      review was performed to identify 25 patients who underwent RAH/P + PAL for stage
      I carcinoma of the cervix from 1990 to 1998 through a nonmuscle splitting
      (Pfannenstiel) abdominal incision. All patients were seen and had follow-up in
      the Division of Gynecologic Oncology, University of Miami School of
      Medicine/Jackson Memorial Medical Center (Miami, FL). Data were collected on
      various clinical and surgical parameters including height/weight, operative time,
      blood loss, number of lymph nodes obtained, length of hospital stay, and
      postoperative complications. Analysis of the data revealed that operative time
      and average blood loss were within acceptable parameters. The yield at
      lymphadenectomy for pelvic and para-aortic lymph nodes was also respectable.
      Postoperative complications were minimal and there were no wound complications
      reported. Therefore, the Pfannenstiel incision can be safely utilized in a select
      group of patients undergoing RAH/P + PAL.

PMID- 11240805
TI  - Clinical significance of tumor size in stage IB and II carcinoma of the uterine
      cervix.
AB  - The purpose of the present study was to investigate the correlation between tumor
      size and prognosis in stage IB and II cervical cancer and to elucidate the
      adequacy of new FIGO staging system for cervical cancer. The subjects included
      128 patients with cervical cancer (stage IB = 86, IIA = 18, and IIB = 24) who had
      undergone radical hysterectomy. The largest tumor size of the pathology specimen
      was measured in two dimensions, and the correlation between tumor size and
      prognosis was investigated. In addition, tumor size of the pathology specimen was
      compared with the largest tumor diameter measured by MRI in stage IB cancers.
      Patients with a tumor size greater than 3 cm2 had a significantly worse 5-year
      survival rate (63%) when compared to those with tumor size no greater than 3 cm2
      (96%) (P < 0.0001). Multivariate analysis revealed that independent prognostic
      factors were tumor size (P = 0.003) and lymph node metastasis (P = 0.015). By
      regression analysis, the largest tumor size of the pathology specimen was
      relatively well correlated with the largest tumor diameter by MRI in stage IB
      cancers; 3 cm2 of tumor size in the pathology specimen corresponded to 3.4 cm of
      tumor diameter by MRI. The adequacy of new FIGO staging system was considered
      relatively acceptable.

PMID- 11240806
TI  - Tumor cytotoxicity of peritoneal macrophages and peripheral blood monocytes from
      patients with ovarian, endometrial, and cervical cancer.
AB  - The purpose of this study was to compare the cytotoxic capacity of peritoneal
      macrophages (PM) and peripheral blood monocytes (PBM) from patients with ovarian,
      endometrial, and cervical cancers after in vitro activation with gamma interferon
      (IFN-gamma) and lipopolysaccharide (LPS). Peritoneal macrophages were obtained
      from ascites or peritoneal washings and peripheral blood monocytes via peripheral
      venipuncture from 58 patients: 17 with ovarian, 19 with endometrial, and 10 with
      cervical cancers. PBM and PM from 12 patients with nonmalignant gynecologic
      conditions served as controls. Cytotoxicity was assessed by the ability of PBM
      and PM to lyze Cr51-labeled Chang hepatoma cells. Activated peripheral blood
      monocytes of ovarian and endometrial cancer patients and peritoneal macrophages
      from ovarian cancer patients were significantly more cytotoxic than those from
      nonactivated controls. Activated PBM and PM from cervical cancer and PM from
      endometrial cancer did not demonstrate increased cytotoxicity compared to
      nonactivated controls. There was no significant correlation of the cytotoxicity
      with grade, stage, differentiation or age of the cancers. These in vitro data
      would suggest that ovarian cancer and possibly endometrial cancer should receive
      further evaluation and consideration of cytokine-based and/or adoptive cellular
      immunotherapy.

PMID- 11240807
TI  - Neuroendocrine signet ring cell adenocarcinoma of the endocervix.
AB  - Signet ring cell morphology in mixed carcinoma of the uterine cervix is not
      uncommon. It is rare for such morphology to predominate, however, and there are
      no reported cases of a signet ring cell adenocarcinoma (SRCA) of the endocervix
      with neuroendocrine differentiation. A 53-year-old woman presented with abnormal
      perimenopausal bleeding, and uterine curettings revealed a signet ring cell
      carcinoma. After clinical evaluation to eliminate a metastasis from an extra
      uterine primary, the patient underwent surgical therapy and staging, and was
      treated with postoperative adjuvant chemoradiation. Pathologic evaluation found
      the tumor to arise from the endocervix and to be of predominant signet ring cell
      morphology. Immunohistochemical staining revealed that the tumor exhibited
      neuroendocrine differentiation and helped confirm its endocervical origin. The
      patient remains without evidence of disease 6 months after primary therapy. This
      is the first case report of endocervical SRCA with neuroendocrine differentiation
      (SRCA with features of carcinoid tumor). Discussion of this entity is provided.

PMID- 11240808
TI  - Radiation Therapy Oncology Group clinical trials for carcinoma of the cervix.
AB  - Grigsby PW. Radiation Therapy Oncology Group clinical trials for carcinoma of the
      cervix. The purpose of this paper is to review the primary data of the clinical
      trials performed by the Radiation Therapy Oncology Group (RTOG) for patients with
      carcinoma of the uterine cervix. The trials, their strengths, limitations, and
      the implications of the results are discussed. During the past 25 years there
      have been several clinical trials performed by the RTOG to test various
      hypotheses for improving local control and survival for patients with carcinoma
      of the uterine cervix. The major research themes that have been appraised are the
      use of hyperbaric oxygen, altered fractionation radiotherapy, hypoxic cell
      sensitization, chemo-sensitization, prophylactic paraaortic irradiation, and
      neutron radiotherapy. There are two general research themes. The initial RTOG
      trials for cervical cancer attempted to address the issues of tumor volume and
      hypoxic cells while the latter studies addressed these issues and the issue of
      micrometastatic disease. The phase III clinical trials performed by the RTOG have
      not demonstrated a local control or survival advantage in the experimental arm
      with the use of hyperbaric oxygen, split-course radiotherapy, hypoxic cell
      sensitization, or neutron radiotherapy. Acceptable toxicity and efficacy results
      were shown in phase II studies evaluating twice-daily irradiation and chemo
      sensitization. The positive phase III trials were RTOG 79-20 which evaluated
      prophylactic paraaortic irradiation in patients with bulky stages IB, IIA, and
      IIB disease, and RTOG 90-01 which evaluated concurrent chemotherapy. Results of
      more recent clinical trials are pending their completion.

PMID- 11240809
TI  - Tolerance of twenty-four hour paclitaxel and carboplatin as first-line therapy in
      ovarian, peritoneal and fallopian tube carcinoma.
AB  - Rose PG, Fusco N, Fluellen L, Rodriguiz M. Tolerance of twenty-four hour
      paclitaxel and carboplatin as first-line therapy in ovarian, peritoneal and
      fallopian tube carcinoma. A combination of a platinum and taxane are accepted as
      standard first-line therapy for ovarian cancer. However, both 24-h paclitaxel and
      cisplatin and 3-h paclitaxel and carboplatin have significant neurotoxicity. The
      present study was undertaken to determine the toxicity of 24-h paclitaxel and
      carboplatin as first-line therapy. Ovarian, peritoneal, and fallopian tubal
      carcinoma patients treated with 24-h paclitaxel and carboplatin as first-line
      therapy were retrospectively reviewed. Paclitaxel was administered at a dose of
      135 mg/m2 as a 24-h infusion followed by carboplatin at an AUC of 5 every 21
      days. Toxicity was graded according to NCI Common Toxicity Scale. Fourteen
      patients with ovarian, peritoneal or tubal carcinoma were studied. Twelve were
      treated primarily with paclitaxel and carboplatin and two were originally treated
      with paclitaxel and cisplatin for two cycles but switched to paclitaxel and
      carboplatin for severe cisplatin-associated toxicities. A total of 86 courses
      were administered (median 6, range 1-9). Hematologic toxicity was the principal
      toxicity with neutropenic fever occurring in 8 patients (57%). The duration of
      neutropenia was brief and no septic deaths occurred. Following paclitaxel dose
      reduction to 110 mg/m2 neutropenic sepsis did not recur except in one patient
      with recurrent C. difficile colitis. The two patients who switched from
      paclitaxel/cisplatin to paclitaxel/carboplatin reported better tolerance of the
      chemotherapy regimen. Among the 13 patients with ovarian and peritoneal carcinoma
      100% achieved a clinical complete response. Although associated with a high
      incidence of neutropenia, this regimen had rare severe or chronic toxicities in
      particular neurotoxicity and a high response rate.

PMID- 11240810
TI  - Presence of asbestos in peritoneal malignant mesotheliomas in women.
AB  - Heller DS, Gordon RE, Clement PB, Turnnir R, Katz N. Presence of asbestos in
      peritoneal malignant mesotheliomas in women. Asbestos plays a causal role in
      pleural mesotheliomas. The role in peritoneal mesotheliomas is less clear,
      particularly in women, who are less likely to have an exposure history. Seven
      peritoneal malignant mesotheliomas in women with no recorded asbestos exposure
      were analyzed in this report. Tissue digestion was performed on paraffin blocks
      of tumor. Transmission electron microscopy, energy-dispersive spectroscopy, and
      electron diffraction were performed for tissue fiber burden and fiber
      identification. Asbestos fiber burdens were present in 6 cases. Two showed
      crocidolite, 2 showed chrysotile, one showed chrysotile and amosite, and one
      showed chrysotile and tremolite. Fiber burdens ranged from 56,738 to 1,963,250
      fibers per gram wet weight tissue. All fibers counted were between 1 and 5
      microns. This study demonstrates asbestos in peritoneal mesotheliomas in women.
      Asbestos may play a role in the development of these tumors.

PMID- 11240811
TI  - Outpatient vaginal cuff brachytherapy for endometrial cancer.
AB  - Petereit DG, Tannehill SP, Grosen EA, Hartenbach EM, Schink JC. Outpatient
      vaginal cuff brachytherapy for endometrial cancer. The objective of this study
      was to determine the efficacy and complications of postoperative high-dose-rate
      (HDR) vaginal-cuff brachytherapy (VCB) in patients with endometrial carcinoma.
      Between August 1989 to September 1997, 191 patients were treated postoperatively
      after a total abdominal hysterectomy and bilateral salpingo-oophorectomy
      (TAH/BSO) with outpatient adjuvant HDR VCB for low-risk endometrial cancer (IB
      84%, grade 1 or 2-96%). Patients were treated with 2 HDR fractions, delivered one
      week apart while under conscious sedation (16.2 Gy X 2 to the vaginal surface).
      All clinical endpoints were calculated using the Kaplan Meier method. The median
      time in the brachytherapy suite was 60 min in which no acute complications were
      observed. The 30-day morbidity and mortality rates were both 0%. With a median
      follow-up of 38 months (12-82 months), the 4-year survival, relapse-free
      survival, and vaginal-control rates were 95%, 98%, and 100%, respectively. One
      patient developed a colo-vaginal fistula at 5 years. Adjuvant HDR VCB in 2
      outpatient insertions produced 100% vaginal control rates with minimal morbidity.
      The advantages of high dose-rate compared to low dose-rate vaginal brachytherapy
      include patient convenience, markedly shorter treatment times (1 h per
      insertion), and reduction in the cost and potential morbidity of hospitalization.
      HDR brachytherapy approach is a cost-effective alternative to either low-dose
      rate brachytherapy or whole pelvic radiotherapy in carefully selected patients.

PMID- 11240812
TI  - The treatment of uterine papillary serous carcinoma (UPSC): are we doing the
      right thing?
AB  - Tay EH, Ward BG. The treatment of uterine papillary serous carcinoma (UPSC): are
      we doing the right thing? In an earlier study(1) of 21 patients with uterine
      papillary serous carcinoma (UPSC), Ward et al. found a poor 3-year survival, even
      for patients with surgically documented localized disease, and a high rate of
      recurrence outside the field of treatment. Eight years later, we performed a
      retrospective study on 67 patients who were treated initially by surgery, which
      included the 21 patients previously reported, to evaluate any changes in the
      management approach since 1990 and its impact on the survival of such patients.
      The clinical characteristics of patients treated before and after 1990 were
      similar. However, after 1990, more patients had omentectomy and complete surgical
      staging (42% vs. 17%); chemotherapy was more widely used (63% vs. 33%); all
      chemotherapies were platinum-based regimens and less radiotherapy was
      administered (47% vs. 83%). The overall 3-year survival was 43% and 5-year
      survival was 35%, with a median survival period of 31 months. There was no
      significant difference in the survival outcome between patients managed before
      and after 1990, after adjusting for stage and spread of disease. Based on the
      results of this retrospective study, it appears that the current treatment
      strategy has not resulted in an improvement in the survival of patients with
      UPSC.

PMID- 11240813
TI  - Analysis of initial failure site and spread pattern in endometrial carcinoma: a
      Japanese experience.
AB  - Kasamatsu T, Shiromizu K, Takahashi M, Matsumoto K, Shirai T. Analysis of initial
      failure site and spread pattern in endometrial carcinoma: a Japanese experience.
      This retrospective study was undertaken in an attempt to identify initial failure
      sites and spread patterns in patients with endometrial carcinoma in Japan. A
      retrospective clinicopathologic review of 272 patients treated from 1983 to 1994
      at Saitama Cancer Center was performed. Patients underwent total hysterectomy,
      bilateral salpingo-oophorectomy and pelvic lymphadenectomy. Postoperative
      external radiation was given to the patients with deep myometrial invasion, high
      grade tumor, and/or lymph node metastasis. Following surgery, chemotherapy was
      given to the patients with extrapelvic metastasis. Of the 272 patients, 262 had
      no residual disease after initial treatment and 10 had confirmed residual
      disease. Of the 262 patients, 32 (12.2%) suffered recurrence. The recurrence
      rates for stage I, II, III, and IV were 5.6% (10/178), 5.7% (2/35), 35.3%
      (18/51), and 100% (2/2), respectively. Of the 32 patients who failed, 6 (18.8%)
      experienced local failure, 13 (40.6%) had distant failure without peritoneal
      spread, and 13 (40.6%) had distant failure with peritoneal spread. In distant
      failure, the incidence of peritoneal spread was highest (50.0%, 13/26), closely
      followed by that of pulmonary metastasis (46.2%, 12/26). Furthermore, of those
      patients with residual disease, peritoneal spread was found in 80% (8 of 10).
      Five of the six patients (83.3%) with local failure survive, but all patients
      with peritoneal spread have died. Peritoneal dissemination is an important
      failure pattern and should be considered a top priority in an attempt to improve
      survival in patients with endometrial carcinoma.

PMID- 11240814
TI  - Clinical relevance of retroperitoneal involvement from epithelial ovarian tumors
      of borderline malignancy.
AB  - Rota SM, Zanetta G, Ieda N, Rossi R, Chiari S, Perego P, Mangioni C. Clinical
      relevance of retroperitoneal involvement from epithelial ovarian tumors of
      borderline malignancy. Ovarian tumors of borderline malignancy have an
      outstanding prognosis. The need for aggressive surgical staging is questionable
      and the need for retroperitoneal node sampling is debated. From 1982 to 1996, 81
      women underwent surgical staging including retroperitoneal sampling. Three
      patients (3.7%) with serous tumor had microscopic nodal involvement.
      Retroperitoneal metastases were found in two intraperitoneal stage I tumors and
      in one stage IIIA tumor. Positive nodes were found in 1/31 (3.2%) women
      undergoing sampling of para-aortic nodes and in 2/69 (2.8%) women undergoing
      sampling of pelvic nodes. With a median follow-up of 79 months we observed five
      recurrences, but none involved the retroperitoneum. The three patients with
      positive nodes remain alive without disease. Among 236 patients with diagnosis of
      borderline tumor but without sampling of the nodes, we observed one
      retroperitoneal recurrence (0.4%) in a serous tumor. There are no indications for
      retroperitoneal sampling of mucinous borderline tumors. For serous tumors this
      procedure should only be performed as a part of prospective trials. The clinical
      relevance of retroperitoneal involvement in borderline tumors appears minimal and
      does not justify routine aggressive surgery.

PMID- 11240815
TI  - Pretreatment evaluation of adnexal tumors predicting ovarian cancer.
AB  - Kobal B, Rakar S, Ribic-Pucelj M, Tomazevie T, Zaletel-Kragelj L. Pretreatment
      evaluation of adnexal tumors predicting ovarian cancer. The objective of this
      study was to determine the ability of tumor marker assessment, gray-scale
      transvaginal with color Doppler ultrasonography to predict ovarian malignancy.
      One hundred thirty-four subjects with ovarian masses who entered the study
      prospectively underwent pelvic examination, tumor marker assessment and gray
      scale transvaginal with color flow Doppler ultrasonography preoperatively.
      Malignancy predictors were statistically evaluated with stepwise multiple
      logistic regression, and the scores from the model were transformed to
      probability for having a malignant disease. The presence of neovascularization,
      intracystic papillary projections, elevated serum CA 125, and age over 45 years
      were significant predictors for malignancy. Positive predictive value (PPV) for
      the regression model was 89.0%, and negative predictive value (NPV) was 96.8%.
      Probability for malignancy ranged from 0.004 to 0.991 depending on which
      covariates were included. Logistic regression analysis of pretreatment diagnostic
      gray-scale and color Doppler ultrasonographic characteristics, together with CA
      125 enabled a creation of probability assessment scale for individual estimation
      of ovarian mass, which may contribute to final clinical decision.

PMID- 11240816
TI  - Pattern of CIN recurrence following laser ablation treatment: long-term follow
      up.
AB  - Chew GK, Jandial L, Paraskevaidis E, Kitchener HC. Pattern of CIN recurrence
      following laser ablation treatment: Long-term follow-up. Our objective was to
      study the long-term patern of recurrence of cervical intraepithelial neoplasia
      (CIN) and development of cervical carcinoma in patients who had been treated with
      laser ablative treatment. The study design consisted of a retrospective analysis
      of the case records of 2130 patients who received laser ablation treatment for
      CIN lesions from 1980-1988, with the years 1980 and 1988 inclusive. All of the
      2130 women in the cohort have had at least seven years of follow-up. Of the
      treated population, 79% remain under regular cytological follow-up at the
      regional laboratory. Nine percent required further treatment, 52% of this within
      the first year of treatment, 19% within the second year, 4% in the third, 5% in
      the fourth and fifth years, and 15% over the next five years. These lesions were
      detected up to ten years after the initial treatment. No recurrent lesions have
      yet been detected after ten years, and 0.2% of the cohort have developed cervical
      carcinoma. Long-term follow-up has demonstrated a continuing incidence of
      recurrent CIN up to ten years after initial treatment. This emphasizes the need
      for adherence to follow-up protocol if the incidence of cervical carcinoma post
      treatment is to be reduced. The data suggest that annual follow-up for 10 years
      may be advisable to reduce the risk of post-treatment invasive disease.

PMID- 11240817
TI  - The experience of long-term hospital follow-up for women who have suffered early
      stage gynecological cancer: a qualitative interview study.
AB  - Bradley EJ, Pitts MK, Redman CWE, Calvert E. The experience of long term hospital
      follow-up for women who have suffered early stage gynecological cancer: a
      qualitative interview study. The objective of this paper is to investigate the
      factors involved in the wish for continuing long-term follow-up for early stage
      gynecological cancer in the absence of obvious clinical benefit. This qualitative
      study is comprised of semistructured, individual interviews. Twelve women who had
      been treated for early stage (I-II) gynecological cancer (cervical, vulval,
      ovarian, endometrial) and had been attending regular follow-up appointments at
      the hospital clinic for a minimum of six months were interviewed for this study.
      The primary outcome measures were women's views on their follow-up needs. Women
      who continue to express a need for follow-up appointments years after the
      treatment of active disease are seeking to alleviate anxiety regarding possible
      recurrent illness. The main element of follow-up that alleviates this recurrence
      anxiety is medical reassurance, this is only judged to be worthwhile when given
      by a gynecological consultant. There is a difficulty with regarding the period of
      remission as a healthy state, both cultural "lay" beliefs and family support
      exacerbate this difficulty. Although family support is deemed important
      initially, it may actually serve to maintain "sickness" identity, perpetuating
      views of cancer remission as another stage of illness. We conclude that the
      processes involved in follow-up for cancers with a very low recurrence risk are
      complex. Follow-up information is perhaps medical, but women who have a continued
      need for follow-up in the absence of any clinical disease are attending for
      psychological purposes. Further research is needed to study possible
      interventions that could be introduced to help alleviate anxiety during the
      period of cancer recovery.

PMID- 11240818
TI  - Ovarian cancer identified through screening with serum markers but not by pelvic
      imaging.
AB  - Woolas RP, Oram DH, Jeyarajah AR, Bast RC Jr, Jacobs IJ. Ovarian cancer
      identified through screening with serum markers but not by pelvic imaging. This
      study evaluated the possible role of 3 additional tumor markers to CA 125 among
      postmenopausal volunteers participating in a sequential multimodal ovarian cancer
      screening study. In 82 asymptomatic women the finding of a serum CA 125 level of
      > 30 U/ml precipitated pelvic ultrasound examination. Levels of CA15-3, CA72-4
      and CA19-9 were subsequently determined in sera stored from the time of the CA
      125 assay. Following ultrasound 29 women underwent surgery for benign conditions.
      The remaining 53 women underwent 2 years of surveillance. In 5 of these women a
      diagnosis of ovarian cancer was established between 6 and 10 months after their
      initial investigation. Elevated levels of at least one of the 3 additional tumor
      markers were present in the serum, prior to ultrasound abnormalities being
      detected, in 4 (80%) of the women who developed cancer. At least one of this 3
      marker panel was elevated in 29% of the 48 women who have not developed cancer
      and 14% of the 29 women undergoing surgery for benign conditions. Information
      complementary to pelvic ultrasound examination for the preclinical detection of
      ovarian cancer could be obtained through multiple marker assay. Coordinated
      elevated serum levels of tumor markers could increase the sensitivity of this
      sequential screening protocol.

PMID- 11240819
TI  - Peritoneal fluid gonadotropins and ovarian hormones in patients with ovarian
      cancer.
AB  - Halperin R, Hadas E, Langer R, Bukovsky I, Schneider D. Peritoneal fluid
      gonadotropins and ovarian hormones in patients with ovarian cancer. The aim of
      this study was to examine the hormonal milieu in peritoneal fluid in ovarian
      cancer and control patients, and to try to identify hormonal parameters specific
      for ovarian cancer. The study included 41 patients: 21 with ovarian cancer and 20
      patients with benign disease, constituting a control group. The peritoneal fluid
      and serum samples from these patients were subjected to analysis of follicle
      stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2),
      progesterone, testosterone, androstenedione, and dehydroepiandrosterone sulfate
      (DHEAS), and levels were compared between the two study groups. In addition,
      peritoneal fluid samples were subjected to cytologic examination and serum
      samples were assayed for CA 125. All the examined hormonal parameters in
      peritoneal fluid demonstrated a significant increase in ovarian cancer compared
      to control patients (P < 0.04). No significant difference in serum levels of the
      measured hormones was observed between the 2 groups. In order to further
      discriminate between patients with and without ovarian cancer, the sensitivity,
      specificity, positive and negative predictive values, and diagnostic accuracy of
      each parameter were calculated. Determination of LH in peritoneal fluid provided
      sensitivity, specificity and diagnostic accuracy of 100%. In conclusion, patients
      with ovarian cancer as compared to controls demonstrate significantly increased
      levels of gonadotropins and ovarian hormones in peritoneal fluid, thus supporting
      the theory of association between ovarian cancer and specific hormonal milieu. In
      addition, our results provide a novel hormonal marker for discrimination between
      patients with and without ovarian cancer.

PMID- 11240820
TI  - Skin bridge recurrences in vulvar cancer: frequency and management.
AB  - Rose PG. Skin bridge recurrences in vulvar cancer: frequency and management. The
      use of separate groin incisions has markedly reduced the rate of wound breakdown
      from radical vulvectomy. This retrospective review was undertaken to evaluate the
      frequency and management of skin bridge recurrences. Five cases of skin bridge
      recurrence in vulvar cancer were identified among 128 patients. Patient
      demographics, pathology, recurrence management, and follow-up were obtained from
      operative and clinical records and tumor registries. Five cases of isolated skin
      bridge recurrence were studied, of which four patients had squamous cancer and
      one melanoma. Excluding one case referred at recurrence, this occurred in 2.4% of
      patients with squamous cell carcinoma and was more common in patients with
      positive nodes 3 of 41 patients versus 0 of 85, relative risk 3.07 (95%
      confidence interval 2.39-3.95). The median time to recurrence following surgery
      was 4.0 months (range 1-47 months). Four recurrences were treated by radical
      local excision alone, but 3 had already received radiation therapy. One patient
      developed a second skin bridge recurrence and was treated with a second radical
      local excision. Three patients are alive and recurrence-free 38+ to 56+ months
      (median 51+ months) following treatment for recurrence. Skin bridge recurrences
      are rare and more common in patients with inguinal node metastasis. Local
      excision with or without radiation therapy is the most common therapy that has
      been employed. In the absence of other metastases local excision is associated
      with a good recurrence-free survival.

PMID- 11240821
TI  - Fulminant Clostridium difficile colitis associated with paclitaxel and
      carboplatin chemotherapy.
AB  - Resnik E, LeFevre CA. Fulminant Clostridium difficile colitis associated with
      paclitaxel and carboplatin chemotherapy. Pseudomembranous colitis is commonly
      associated with the use of antibiotics. Some antineoplastic agents even without
      associated antibiotic use can predispose patients to developing infection with
      Clostridium difficile. The infection is usually mild; however, in rare cases
      severe forms of pseudomembranous colitis may be encountered. A 66 year-old female
      with stage IIIC suboptimally debulked epithelial ovarian cancer was treated with
      paclitaxel and carboplatin. the patient developed fulminant C. difficile colitis
      three weeks after the second cycle of chemotherapy. Severe symptoms began 24 h
      prior to admission; however, mild nausea and diarrhea had been present for a week
      despite self-treatment with over-the-counter Imodium and Pepto-Bismol. Her last
      antibiotic use was seven weeks previously. The patient was hospitalized
      immediately for aggressive treatment. Notwithstanding all the efforts, her
      condition continued to deteriorate and she expired. Severe C. difficile colitis
      can be life threatening. Patients undergoing chemotherapy who develop significant
      diarrhea should be evaluated for C. difficile. Prompt diagnosis and intervention
      prior to onset of severe symptoms can potentially improve the outcome.

PMID- 11240822
TI  - Necessity of re-evaluation of estramustine phosphate sodium (EMP) as a treatment
      option for first-line monotherapy in advanced prostate cancer.
AB  - Estramustine phosphate sodium (EMP) was first introduced in the early 1970s for
      the treatment of prostate cancer, when EMP was supposed to have the dual effect
      of estrogenic activity and cytotoxicity. For the following decades, it was used
      mainly in hormone-refractory cases, with a conventional dosage of 4-9
      capsules/day, which showed a 30-35% objective response rate. However, a very
      limited number of cases have been reported that used EMP as a first-line
      monotherapy in the conventional dosage. One study showed a response rate of 82%,
      which is at least as effective as conventional estrogen (diethylstilbestrol; DES)
      monotherapy. Nevertheless, EMP was almost abandoned for the treatment of prostate
      cancer because of severe adverse side-effects, especially in the cardiovascular
      system and gastrointestinal tract. Recently, two facts have become evident.
      First, EMP interferes with cellular microtubule dynamics but does not show
      alkylating effects. Second, EMP is able to produce a complex with calcium when
      dairy products are taken concomitantly with EMP, resulting in a decrease in the
      absorption rate of EMP from the gut. Many clinical trials have been undertaken
      without warning against concomitant dairy product intake since the introduction
      of EMP. This fact will jeopardize almost all the clinical trials performed before
      1990. It is considered that response rates have been underestimated and better
      results could have been obtained because side-effects decrease dose-dependently.
      Low-dose EMP monotherapy (2 capsules/day) has been performed infrequently in
      previously untreated advanced prostate cancer. The only large trial by the
      European Organization for Research and Treatment of Cancer in 1984 was biased in
      selecting patients. Nevertheless, the response rate of EMP is comparable to that
      of DES. In this study, the adverse side-effects of EMP were less than that of
      DES. Recently, a study was conducted at the University of Tokyo of 11 patients
      with advanced prostate cancer on low-dose EMP as first-line monotherapy. The
      study found that the mean serum prostate-specific antigen level decreased to
      within the normal range by day 50; mean serum testosterone, leutinizing hormone
      and follicle-stimulating hormone reduced to undetectable levels by day 20; and
      mean serum estradiol increased to a very high level within 1 week. These data
      implicate that low-dose EMP can suppress quickly and adequately the pituitary
      gonadal axis, although the antitumor effect has not as yet been elucidated. For
      these reasons, it is necessary to re-evaluate low-dose EMP monotherapy in
      previously untreated advanced prostate cancer.

PMID- 11240823
TI  - Evaluation of the efficacy and safety of laparoscopic nephrectomy.
AB  - PURPOSE: To evaluate the efficacy and safety of laparoscopic nephrectomy.
      METHODS: From June 1994 to November 1999, 10 patients underwent laparoscopic
      nephrectomy at Osaka University Medical Hospital and Osaka Rosai Hospital.
      Laparoscopic nephrectomy was performed either via transperitoneal or
      retroperitoneal approach under general anesthesia. These 10 cases were reviewed
      in respect of primary disease of the kidney, operative time, complications and
      postoperative convalescence. RESULTS: Of the 10 patients, five were
      preoperatively diagnosed as having a non-functioning kidney with hydronephrosis,
      two patients were diagnosed as having an atrophic kidney, two had renal cell
      carcinoma and one had renal pelvic tumor. The average operative time was 374 min
      (range 270-675 min). The mean blood loss was 330 mL (range 60-800 mL). One
      patient required transfusion due to postoperative oozing. The average hospital
      stay after operation was 7 days. No major postoperative complications were
      observed. CONCLUSION: Laparoscopic nephrectomy is an option in surgically
      managing renal disorders, including malignancies, although it has a longer
      operative time compared to conventional open surgery.

PMID- 11240824
TI  - Magnetic resonance imaging and morphometric histologic analysis of prostate
      tissue composition in predicting the clinical outcome of terazosin therapy in
      benign prostatic hyperplasia.
AB  - PURPOSE: To determine whether magnetic resonance imaging (MRI) or quantitative
      color-imaged morphometric analysis (MA) of the prostate gland are related to the
      clinical response to terazosin. METHODS: Thirty-six male patients with
      symptomatic benign prostatic hyperplasia (BPH) with a serum prostate-specific
      antigen level of 4-10 ng/mL underwent MRI with body coil, transrectal prostate
      ultrasonography and biopsy prior to terazosin therapy. For MRI-determined stromal
      and non-stromal BPH, the ratio of the signal intensity of the inner gland to the
      obturator internus muscle was evaluated. Histologic sections were stained with
      hematoxylin and eosin. The MA of the specimens was performed by Samba 2000.
      Results of the two techniques were interpreted according to the terazosin therapy
      results. RESULTS: The mean stromal percentage was 60.5 +/- 18.0%. No
      statistically significant relationship was found between the clinical outcome of
      terazosin and the MRI findings. The MA results showed a significant relationship
      between the percentage of stroma and the percent change of the peak urinary flow
      rate, but not with the percent change of the international prostate symptom score
      after terazosin therapy (P < 0.05). CONCLUSION: Magnetic resonance imaging alone
      is not sufficient in predicting the response to terazosin therapy. Morphometric
      analysis of BPH tissue composition can be used in predicting the clinical outcome
      of terazosin therapy but it is suitable only in patients for whom prostatic
      biopsy is necessary in order to rule out prostate cancer.

PMID- 11240825
TI  - Chromosomal variants among 1790 infertile men.
AB  - BACKGROUND: The largest cytogenetic survey involving infertile men was undertaken
      to clarify whether chromosomal abnormalities, including autosomal abnormalities,
      affect semen qualities. METHOD: All male patients who visited an infertility
      clinic from 1990 to 1998 underwent chromosomal and semen analysis. RESULTS:
      Chromosomal abnormalities were found in 225 of 1790 patients (12.6%). The most
      frequent anomaly was Klinefelter syndrome (64 cases). Autosomal anomalies
      accounted for 126 cases. 46,XY,1qh(+) was the most common autosomal anomaly (30
      cases) and its incidence was significantly higher than those of normal controls.
      The seminograms of these patients varied widely, with nine patients having
      azoospermia and three patients achieving natural pregnancies. It is not yet clear
      if this karyotype affects spermatogenesis. CONCLUSION: Autosomal anomalies as
      well as sex chromosomal abnormalities might affect spermatogenesis. Cytogenetic
      study is important before intracytoplasmic sperm injection.

PMID- 11240826
TI  - Age-related prevalence of erectile dysfunction in Japan: assessment by the
      International Index of Erectile Function.
AB  - BACKGROUND: The effects of age and concomitant chronic illness on male sexual
      function were investigated to obtain insight into the prevention of erectile
      dysfunction (ED). METHODS: A questionnaire from the International Index of
      Erectile Function (IIEF) was given to 2311 non-institutionalized men aged 23-79
      years along with a survey of health status. The study sample consisted of 1517
      men who provided complete responses to the questionnaire. For statistical
      analysis, ANOVA was conducted to evaluate the effect of aging on the sexual
      functions and a logistic regression model was used to identify significant
      independent risk factors for ED. RESULTS: There was a significant correlation
      between age and the scores for erectile function, orgasmic function, sexual
      desire and intercourse satisfaction. The prevalence of moderate and severe cases
      of ED were 1.8% and 0% for ages 23-29; 2.6% and 0% for ages 30-39; 7.6% and 1.0%
      for ages 40-49; 14.0% and 6.0% for ages 50-59; 25.9% and 15.9% for ages 60-69;
      and 27.9% and 36.4% for ages 70-79 years, respectively. Hypertension, diabetes
      mellitus, heart disease, chronic hepatitis, disc herniation and cerebral
      infarction under treatment with anticoagulants were significant independent risk
      factors for ED. CONCLUSIONS: The results obtained indicated a significant
      association between aging and chronic diseases and erectile function. Further
      epidemiologic research and analysis of individual risk factors are required to
      allow more effective future strategies for the treatment and prevention of ED.

PMID- 11240827
TI  - Aberrant expression of Pax-2 mRNA in renal cell carcinoma tissue and parenchyma
      of the affected kidney.
AB  - BACKGROUND: Pax proteins are transcription factors that demonstrate oncogenic
      properties and appear to play a crucial role in ontogenesis. Pax-2 is expressed
      in early kidney organogenesis, Wilms' tumor and renal cell carcinoma. In order to
      determine whether the expression of Pax-2 mRNA is a frequent and specific event
      in renal cell carcinoma, its expression in nephrectomized specimens and cell
      lines was investigated. METHODS: The expression of Pax-2 mRNA was examined by
      reverse transcription polymerase chain reaction in 55 nephrectomized specimens,
      nine renal parenchyma specimens from patients without renal cell carcinoma and 16
      cell lines from various malignant diseases. RESULTS: All tumor tissue specimens
      expressed Pax-2 mRNA. In addition, 38 of 55 specimens from the renal parenchyma
      of the affected kidney expressed Pax-2 mRNA. In contrast, only two of the nine
      kidney specimens from patients without renal cell carcinoma expressed Pax-2 mRNA,
      indicating that expression of this protein is significantly higher in renal cell
      carcinoma (P < 0.01). All three cell lines from renal cell carcinoma expressed
      Pax-2. In contrast, Pax-2 was only expressed in two of three cell lines from
      transitional cell carcinoma and in none of the other lines. CONCLUSION: The
      results indicate that Pax-2 expression is a frequent and highly specific event in
      renal cell carcinoma.

PMID- 11240828
TI  - Effect of prostatic neuropeptides on migration of prostate cancer cell lines.
AB  - BACKGROUND: A previous study by the same authors demonstrated that among various
      neuropeptides in the prostate, calcitonin gene-related peptide (CGRP) and gastrin
      releasing peptide (GRP) increased the invasive capacity of PC-3 prostate cancer
      cells through enhancement of cell motility, while substance P (SP) inhibited the
      invasiveness through suppression of motile response. METHODS: The effect of 10
      kinds of neuropeptides were investigated, including CGRP, GRP, SP, neuropeptide Y
      (NPY), vasoactive intestinal polypeptide (VIP), calcitonin (CT), leucine
      enkephalin (L-ENK), methionine-enkephalin (M-ENK), glucagon and parathyroid
      hormone-related protein (PTH-rP), on the invasion of DU-145 prostate cancer cells
      through a reconstituted basement membrane (Matrigel) and the haptotactic
      migration of DU-145, TSU-pr1 and LNCaP prostate cancer cells using a Transwell
      cell culture chamber assay. RESULTS: It was found that GRP, CGRP and PTH-rP
      increased the invasive capacity of tumor cells. In contrast, SP, VIP, CT, L-ENK,
      M-ENK, NPY and glucagon had no significant effect. These three neuropeptides also
      increased the haptotactic migration of tumor cells to fibronectin. In addition
      VIP, CGRP and GRP increased the haptotactic migration of LNCaP prostate cancer
      cells and GRP and PTH-rP increased the migration of TSU-pr1 cells. CONCLUSION:
      The results indicated that some prostatic neuropeptides increased the invasive
      potential of prostate cancer cells partially through enhancement of cell
      motility.

PMID- 11240829
TI  - Lower abdominal phlegmon due to spontaneous rupture of an ileal neobladder.
AB  - A case is presented of spontaneous rupture of an ileal orthotopic neobladder due
      to a large residual urine volume. The present case is the 13th such case
      reported; however, this case is the first to show lower abdominal phlegmon and in
      which the perforation site was detected using computed tomography scanning. The
      indications for neobladder should be considered with great care. If spontaneous
      rupture is suspected, an early diagnosis of the perforation site and a measure of
      the extravasation volume using computed tomography are necessary. Appropriate
      treatment should include laparotomy.

PMID- 11240830
TI  - Bladder stones around a migrated and missed intrauterine contraceptive device.
AB  - Bladder stones occasionally develop because of foreign bodies in the bladder.
      Bladder stones in a 30-year-old woman were found to have formed around an
      intrauterine contraceptive device that had gone missing many years previously and
      had migrated into the bladder. Plain abdominal radiograms should be a part of the
      evaluation in patients with a history of an unretrieved intrauterine
      contraceptive device.

PMID- 11240831
TI  - Repair of a fistula between the bladder and the perineal skin by femoral gracilis
      flap interposition.
AB  - The successful repair of a fistula between the bladder and the perineal skin
      using a femoral gracilis flap is reported. A 70-year-old woman, who 10 years
      previously had undergone a total hysterectomy for uterine cancer, developed a
      fistula between the bladder and the perineal skin after she underwent Mile's
      operation for rectal cancer. Initially, an attempt was made to repair the fistula
      by the transabdominal approach. This failed, probably because of the lack of
      supporting tissue between the bladder and the perineal skin. The second repair
      was performed with plastic surgeons. A secure three-layer bladder closure was
      accomplished. A right femoral gracilis flap was developed and rotated 180 degrees
      to fill the defect in the skin and subcutaneous tissue. Four weeks after surgery,
      cystography revealed no fistula or urinary leakage and the drainage catheter was
      removed. Femoral gracilis flap interposition was successful for repair of a
      fistula between the bladder and the perineal skin when there was no supporting
      tissue due to extensive exenteration in the surgical removal of rectal cancer and
      after other repair procedures had been unsuccessful.

PMID- 11240833
TI  - Penile schwannoma.
AB  - Schwannoma of the penis is extremely rare. A 65-year-old man presented with a
      subcutaneous tumor of penile shaft without any other symptoms. Histopathologic
      examination of the excised tumor revealed benign schwannoma. No recurrence has
      been observed over the 6 months since the surgery.

PMID- 11240832
TI  - Metastases to the penis from carcinoma of the prostate.
AB  - A 58-year-old man presented with dysuria at the Osaka Medical College Hospital in
      November 1996. Laboratory examination revealed elevated serum prostate-specific
      antigen (PSA) to > 100 ng/mL. Adenocarcinoma of the prostate with metastasis to
      the bone was diagnosed after a biopsy of the prostate and bone scintigraphy;
      hormonal therapy was administered. Although bone metastasis was well controlled
      and the serum PSA level declined to within normal levels (2.0 ng/mL), several
      painless nodules were found on the penile glans. Biopsy of the nodules showed
      that the penile tumor was a metastasis from the prostate cancer. The patient
      underwent partial penectomy for relief from penile pain. The serum PSA level
      showed no elevation 3 months after the partial penectomy, suggesting that careful
      observation of prostate cancer patients is necessary, even when oseous metastasis
      is well controlled and serum PSA levels are kept within normal ranges by hormonal
      therapy. The case also indicates that urologists should consider the possibility
      of metastasis to the penis from prostate cancer.

PMID- 11240834
TI  - Deep vein thrombosis during chemotherapy in a patient with advanced testicular
      cancer: successful percutaneous thrombectomy under temporary placement of
      retrievable inferior vena cava filter.
AB  - A 27-year-old man with advanced testicular cancer experienced two events of deep
      vein thrombosis (DVT) during three cycles of cisplatin-based combination
      chemotherapy; the first thrombotic event occurred in the inferior vena cava (IVC)
      following the initial two cycles of chemotherapy and the second thrombotic event
      occurred in the right iliac vein following the third cycle. For both thrombotic
      events, he was successfully managed with thrombolytic therapy and percutaneous
      thrombectomy using a transcatheter hydraulic thrombectomy device under temporary
      placement of a retrievable IVC filter. Stasis of the IVC due to compression by a
      retroperitoneal lymphadenopathy of 7 cm in diameter, which was demonstrated on
      computed tomographic scans at presentation, was considered a major cause of DVT
      during chemotherapy. Patients with bulky retroperitoneal disease causing stasis
      of major veins are at high risk of DVT associated with chemotherapy and
      thromboprophylaxis should be strongly considered during their chemotherapy.

PMID- 11240835
TI  - Reliability and validity of the Intercollegiate Stroke Audit Package.
AB  - The aim of this study was to assure the validity and reliability of the
      Intercollegiate Stroke Audit Package as used in the National Sentinel Audit of
      Stroke. The Intercollegiate Working Party for Stroke, which included most
      stakeholders, including patients, devised the audit standards. These were
      submitted to a formal consensus (modified Delphi) survey before the audit
      questions were developed and piloted for validity and reliability. Following the
      pilot, Help Booklets were developed to promote the involvement of all disciplines
      as auditors in the national sentinel audit of stroke and ensure inter-rater
      reliability. During the national audit each Trust was asked to double rate the
      first five cases with auditors of different disciplines working independently. A
      total of 886 case notes were double-rated in 184 separate sites (median 5, range
      1-5 per site). Trusts used auditors from different disciplines in 77% of cases.
      After excluding the 'No answer' cases the kappa score for items ranged from 0.49
      to 0.87 (median 0.70, IQR 0.63-0.78). Very good agreement was found for seven of
      the 45 items, good agreement for 30 items, and moderate agreement for eight
      items. This large study, across a range of hospital sites and involving many
      disciplines, demonstrates that careful piloting of audit tools, with use of clear
      instructions to auditors, promotes the reliability of data.

PMID- 11240836
TI  - Monitoring the care of lung cancer patients: linking audit and care pathways.
AB  - Clinical audit plays an important role in monitoring the provision of care for
      patients whatever their condition. Care pathways define the steps and expected
      course of events in the care of patients with a specific clinical problem over a
      set time scale. This paper describes a study undertaken in a multisite cancer
      unit to develop a tool for monitoring the progress of lung cancer patients
      through a care pathway and auditing key standards within the pathway. Important
      issues associated with the development of this tool are highlighted. The process
      of developing this tool involved the following steps: a review of the literature
      dealing with the management of lung cancer patients; interviews with key
      personnel in primary, secondary, tertiary and palliative care; development of a
      paper-based series of forms representing key steps in the patient's care pathway;
      3-month trial of the paper-based tool; analysis of completion rates and
      interviews with form users to evaluate effectiveness; and recommendations for
      creating an electronic record using the experience and lessons learned from the
      paper version. The paper forms developed through this multistage process were
      found to be acceptable to users and have the potential to provide accurate
      information at key points for audit throughout the patient's time within the
      health-care system for their lung cancer condition. The flexibility of this
      methodology allows it to be adapted readily to a variety of clinical situations
      and conditions.

PMID- 11240837
TI  - Outcomes-based trial of an inpatient nurse practitioner service for general
      medical patients.
AB  - Although teaching hospitals are increasingly using nurse practitioners (NPs) to
      provide inpatient care, few studies have compared care delivered by NPs and
      housestaff or the ability of NPs to admit and manage unselected general medical
      patients. In a Midwest academic teaching hospital 381 patients were randomized to
      general medical wards staffed either by NPs and a medical director or medical
      housestaff. Data were obtained from medical records, interviews and hospital
      databases. Outcomes were compared on both an intention to treat (i.e. wards to
      which patients were randomized) and actual treatment (i.e. wards to which
      patients were admitted) basis. At admission, patients assigned randomly to NP
      based care (n = 193) and housestaff care (n= 188) were similar with respect to
      demographics, comorbidity, severity of illness and functional parameters.
      Outcomes at discharge and at 6 weeks after discharge were similar (P>0.10) in the
      two groups, including: length of stay; charges; costs; consultations;
      complications; transfers to intensive care; 30-day mortality; patient assessments
      of care; and changes in activities of daily living, SF-36 scores and symptom
      severity. However, after randomization, 90 of 193 patients (47%) assigned to the
      NP ward were actually admitted to housestaff wards, largely because of attending
      physicians and NP requests. None the less, outcomes of patients admitted to NP
      and housestaff wards were similar (P>0.1). NP-based care can be implemented
      successfully in teaching hospitals and, compared to housestaff care, may be
      associated with similar costs and clinical and functional outcomes. However,
      there may be important obstacles to increasing the number of patients cared for
      by NPs, including physician concerns about NPs' capabilities and NPs' limited
      flexibility in managing varying numbers of patients and accepting off-hours
      admissions.

PMID- 11240838
TI  - A comparison of a Bayesian vs. a frequentist method for profiling hospital
      performance.
AB  - The objective of this study was to compare the classification of hospitals as
      outcomes outliers using a commonly implemented frequentist statistical approach
      vs. an implementation of Bayesian hierarchical statistical models, using 30-day
      hospital-level mortality rates for a cohort of acute myocardial infarction
      patients as a test case. For the frequentist approach, a logistic regression
      model was constructed to predict mortality. For each hospital, a risk-adj usted
      mortality rate was computed. Those hospitals whose 95% confidence interval,
      around the risk-adjusted mortality rate, excludes the mean mortality rate were
      classified as outliers. With the Bayesian hierarchical models, three factors
      could vary: the profile of the typical patient (low, medium or high risk), the
      extent to which the mortality rate for the typical patient departed from average,
      and the probability that the mortality rate was indeed different by the specified
      amount. The agreement between the two methods was compared for different patient
      profiles, threshold differences from the average and probabilities. Only marginal
      agreement was shown between the Bayesian and frequentist approaches. In only five
      of the 27 comparisons was the kappa statistic at least 0.40. The remaining 22
      comparisons demonstrated only marginal agreement between the two methods. Within
      the Bayesian framework, hospital classification clearly depended on patient
      profile, threshold and probability of exceeding the threshold. These
      inconsistencies raise questions about the validity of current methods for
      classifying hospital performance, and suggest a need for urgent research into
      which methods are most meaningful to clinicians, managers and the general public.

PMID- 11240839
TI  - Palliative radiotherapy of bone metastases: an evaluation of outcome measures.
AB  - The objective of this study was to identify and evaluate important patient-based
      outcomes that are specific to the palliative radiotherapy of bone metastases. We
      first conducted a literature review to identify and evaluate outcomes that are
      currently in use. To identify outcomes that are important to patients, in-depth
      patient interviews were conducted. Finally, issues identified through the
      interviews were quantified through a prospective survey, in which patients
      completed a questionnaire prior to commencing radiotherapy and again after 6
      weeks. In our literature review, we found that there was no standardized
      definition of either response to radiotherapy or assessment of pain relief. Pain
      measurement in many studies was undertaken using very simple measures, which
      could possibly yield inaccurate results. The vast majority of studies did not
      include quality of life as an endpoint. The patient interviews and survey showed
      that chronic pain and associated limitation of movement were the disease symptoms
      causing the most concern. Having a clear, alert mind and being able in self-care
      were the aspects of daily living given the highest priority. Sustained pain
      relief and minimizing the risk of future complications were the main priorities
      relating to radiotherapy treatment. The practical aspects of treatment
      (travelling distance, remaining at home and brevity of treatment) were of least
      importance. This study indicates the complexity of evaluating the outcomes of
      palliative interventions, and confirms the deficiencies of pain relief as the
      primary end-point. The patient's quality of life is affected by many factors
      other than pain (such as limited mobility, reduced performance, side effects and
      impaired role functioning); hence a wider range of end-points is required.
      Greater sensitivity is required than in currently used end-points. Concurrent
      diseases as well as concurrent therapies can make it difficult to attribute
      effects with precision. Unless such factors are considered in research design,
      the results may prove unreliable.

PMID- 11240840
TI  - Hawthorne effects and research into professional practice.
AB  - The Hawthorne studies in the 1930s demonstrated how difficult it is to understand
      workplace behaviour, and this includes professional performance. Studies of
      interventions to improve professional performance, such as audit, can provide
      useful information for those considering using such methods, but cannot replace
      judgement. In particular, there is no single phenomenon that can be labelled 'the
      Hawthorne effect'. The process of triangulation, considering a subject from
      different perspectives, might overcome the problems of Hawthorne effects better
      than using a single method such as controlled trials.

PMID- 11240841
TI  - An evaluation approach for a new paradigm--health care integration.
AB  - This paper explores an approach to the implementation and evaluation of
      integrated health service delivery. It identifies the key issues involved in
      integration evaluation, provides a framework for assessment and identifies areas
      for the development of new tools and measures. A proactive role for evaluators in
      responding to health service reform is advocated.

PMID- 11240842
TI  - Medicolegal aspect of death: medical referee's input in the aftermath of Shipman.

PMID- 11240843
TI  - Bioinformatic and experimental tools for identification of single-nucleotide
      polymorphisms in genes with a potential role for the development of the insulin
      resistance syndrome.
AB  - OBJECTIVES: Genes with a possible role for the development of the insulin
      resistance syndrome (IRS) were scanned for novel single-nucleotide polymorphisms
      (SNPs) using bioinformatics. METHODS: GenBank mRNA sequences were compared to the
      human EST database using gapped BLAST, software that is available on the
      internet. Mismatches between the search and the EST sequences indicated potential
      SNPs. Thirty-two SNPs in 13 genes were randomly chosen for experimental
      verification. PCR and direct sequencing were used to determine the 'true' SNPs. A
      random sample of 30 Swedish men with slightly elevated diastolic blood pressure
      (85-94 mmHg) obtained from a population-based study was selected for the
      sequencing. After completion of these stages, the potential SNPs were checked
      against the large and rapidly expanding SNP databases HGBASE and NCBI. RESULTS:
      EST searches of 146 genes revealed 106 potential SNPs in 44 genes. Experimental
      analysis of 32 of these potential SNPs verified two SNPs; endothelin receptor A
      1471 G/C (3' UTR) and PAI-1 Trp514Arg from a T/C exchange. These two SNPs were
      also identified in the NCBI and HGBASE databases together with two polymorphisms
      that were not experimentally identified in our homogeneous Swedish population.
      Overall, the HGBASE and NCBI databases contained entries of 22% (23 out of 106)
      of the SNPs identified through our EST searches. CONCLUSIONS: In the search for
      genetic variations causing complex diseases like IRS in homogeneous populations
      (such as the Swedish one used here), important information can be obtained
      through bioinformatic searches of human genome databases and experimental
      verification.

PMID- 11240844
TI  - Sleep-disordered breathing and glucose metabolism in hypertensive men: a
      population-based study.
AB  - OBJECTIVES: Diabetes mellitus and obstructive sleep apnoea (OSA) are two
      prevalent medical problems. Both are strongly associated with obesity and
      hypertension. The aim of this study was to investigate whether the association
      between OSA and diabetes is entirely dependent on obesity in hypertensive men.
      DESIGN: A population-based study. SETTING: The municipality of Uppsala, Sweden.
      Subjects and methods. In 1994, 2668 men aged 40-79 years answered a questionnaire
      regarding snoring, sleep disturbances and somatic diseases. An age-stratified
      sample of 116 hypertensive men was selected for a whole-night sleep study. Twenty
      five of them had diabetes, defined as reporting regular medical controls for
      diabetes or having a fasting blood glucose > or =6.1 mmol L(-1). RESULTS: The
      prevalence of severe OSA, defined as apnoea-hypopnoea index (AHI) > or =20 h(-1)
      was significantly higher in diabetic patients than in normoglycaemic subjects (36
      vs. 14.5%, P < 0.05). The sample was divided into four groups based on the
      presence or absence of severe OSA and the presence or absence of central obesity,
      defined as waist-to-hip ratio (WHR) > or =1.0. In a logistic regression model
      with the non-OSA, WHR <1.0 as the reference group, the adjusted odds ratio (95%
      confidence interval) for diabetes was 11.8 (2.0-69.8) in the OSA, WHR > or =1.0
      group, whilst it was 3.6 (0.9-14.8) in the non-OSA, WHR > or =1.0 group and 5.7
      (0.3-112) in the OSA, WHR <1.0 group. In a linear regression model, after
      adjustment for WHR, there was a significant relationship between variables of
      sleep-disordered breathing and fasting insulin, glucose and haemoglobin A1c.
      CONCLUSIONS: We conclude that, in hypertensive men, although obesity is the main
      risk factor for diabetes, coexistent severe OSA may add to this risk. Sleep
      breathing disorders, independent of central obesity, may influence plasma insulin
      and glycaemia.

PMID- 11240845
TI  - Effect of plant sterol-enriched margarine on plasma lipids and sterols in
      subjects heterozygous for phytosterolaemia.
AB  - OBJECTIVE: Margarine with added plant sterols lowers plasma cholesterol levels.
      It is of importance to know whether these margarines can be used safely in
      carriers of a hereditary disorder with increased absorption of plant sterols.
      DESIGN: In an open feeding study of 8 weeks with a 2-week run-in period and 2
      final weeks as a washout period on control margarine (0.3% plant sterols), two
      obligate heterozygous parents of a patient with classical sitosterolaemia were
      subjected for 4 weeks to a diet containing margarine enriched with plant sterols
      (8%). Fasting blood samples were taken weekly. Primary outcomes were plasma lipid
      and lipoprotein levels and plant sterol levels. RESULTS: Both parents were
      hyperlipidaemic. Total plasma cholesterol levels were decreased by 11 and 12%,
      respectively, after 4 weeks of the consumption of 40 g day(-1) of plant sterol
      enriched margarine. This was mainly due to changes in LDL-cholesterol, whereas
      the other lipoproteins, including lipoprotein(a), were unaffected. Total plant
      sterol levels increased maximally 139% from 0.31 to 0.82% of total sterols in the
      father, and maximally 83% from 0.32 to 0.66% of total sterols in the mother.
      CONCLUSION: An intake of around 3 g day(-1) of plant sterols by subjects
      heterozygous for phytosterolaemia increased campesterol or sitosterol levels in
      blood to similar levels as found in normal subjects. In addition, plasma
      cholesterol levels were reduced to the same extent as in normal or
      hypercholesterolaemic individuals.

PMID- 11240846
TI  - Marked suppression of renin levels by beta-receptor blocker in patients treated
      with standard heart failure therapy: a potential mechanism of benefit from beta
      blockade.
AB  - OBJECTIVES: Recent trials demonstrated beneficial effects of beta-blockers in
      combination with standard heart failure medication. The mechanisms underlying
      this benefit are incompletely understood. We hypothesized that beta-blockers may
      augment the inhibition of the renin-angiotensin system in patients with left
      ventricular (LV) dysfunction treated with angiotensin-converting enzyme (ACE)
      inhibitors and/or diuretics by prevention of renin upregulation that occurs in
      such patients. DESIGN: We examined plasma renin levels (direct radioimmunometric
      assay) in 312 men with previous myocardial infarction (MI) and echocardiographic
      LV dysfunction. Patients took medication according to their physicians'
      prescriptions: antiplatelet agents alone (n=62) or in combination with ACE
      inhibitors, diuretics or beta-blockers (n=250). RESULTS: Plasma renin levels were
      elevated in patients taking ACE inhibitors or diuretics and ACE inhibitors plus
      diuretics (adjusted means from multiple regression analysis were 28.5 mU L-1 [95%
      CI=20.6-39.5] and 73.7 mU L-1 [95% CI = 49.9- 109.9], respectively) compared with
      patients on antiplatelets alone (16.1 mU L-1, 95% CI = 13.5-19.3, P < 0.05 each).
      The combinations of beta-blockers with ACE inhibitors or diuretics and beta
      blockers with ACE inhibitors plus diuretics were related to markedly suppressed
      plasma renin levels (adjusted means 16.4 [13.1-20.6] and 32.1 [23.3-44.3]) as
      compared with respective patient groups without beta-blockers (P < 0.01 each).
      CONCLUSIONS: Concomitant beta-blocker treatment can prevent the reactive renin
      stimulation and potentially the escape from effective inhibition of the renin
      angiotensin system in patients with LV dysfunction after MI treated with ACE
      inhibitors and/or diuretics.

PMID- 11240847
TI  - Almost all institutionalized women are osteoporotic, when measured by heel and
      finger ultrasound.
AB  - OBJECTIVES: Since there is a need for simple methods to identify individuals with
      osteoporosis, we investigated bone status (heel and finger) with ultrasound in an
      institutionalized elderly population and studied the association between these
      measures, risk factors for osteoporosis and prevalent osteoporotic fractures.
      DESIGN: Cross-sectional study. Subjects. Nursing home residents, 237 women and 84
      men, mean age 84 years. RESULTS: Altogether 82% of those eligible could undergo
      heel ultrasound, 65% finger ultrasound and 41% measurements at both sites. Using
      a transcription of the WHO criterion of osteoporosis, 95% of the women who
      underwent heel ultrasound were classified as osteoporotic (mean T-score = -4.8)
      and 92% had Z-scores below zero (mean Z-score=-1.6), whereas 51% of the men were
      osteoporotic (mean T-score=-2.6) and 77% had Z-scores below zero (mean Z-score=
      1.3). Based on finger ultrasound measurements, 99% of the women were classified
      as osteoporotic (mean T-score=-5.0) and 93% had Z-scores below zero (mean -1.6).
      The variations in ultrasound values were only moderately explained by age,
      current weight and walking ability. Amongst women, the association with a
      prevalent osteoporotic fracture decreased by 43% (95% CI=10-63%) for every SD
      increase in speed of sound (SOS) of the heel, but no such relationship was found
      for finger SOS. CONCLUSIONS: Our results from ultrasound measurements at two
      different anatomical sites indicate that virtually all institutionalized elderly
      women could be classified as osteoporotic, when measured by these techniques.

PMID- 11240848
TI  - Identification of a new coeliac disease subgroup: antiendomysial and anti
      transglutaminase antibodies of IgG class in the absence of selective IgA
      deficiency.
AB  - OBJECTIVE: The aim of the present study was to increase the sensitivity of the
      antiendomysial antibody (EMA) test by evaluating also EMAs of IgG1 isotype.
      DESIGN AND SUBJECTS: Over the last 2 years, serum EMAs IgA and IgG1 were
      determined in 1399 patients, referred to our gastrointestinal unit due to
      clinical suspicion of malabsorption. Serum anti-tissue transglutaminase (tTG)
      antibodies IgA and IgG, as well as total IgA levels, were also investigated.
      Furthermore, EMAs IgA and IgG1 were evaluated in biopsy culture supernatants.
      Biopsy specimens were also admitted to histological and immunohistochemical
      evaluation. Twenty-six patients with gastroenterological disease other than
      coeliac disease (CD) were used as a disease control group. Ninety-nine blood
      donors were used as a healthy control group. RESULTS: Diagnosis of CD was based
      on histological findings in the 110/1399 patients showing EMA IgA positivity, and
      in a further 56/1399 patients presenting both EMA IgA and IgG1 positivity in sera
      as well as in culture supernatants. Of the remaining 1233 EMA IgA-negative
      patients, 60 showed only EMA IgG1 positivity both in sera and in culture
      supernatants. It is noteworthy that anti-tissue transglutaminase antibodies IgG
      (anti-tTG) were positive in all 60 EMA IgG1-positive patients as well. By
      contrast, a selective IgA deficiency was found in only 11 out of the 60 EMA IgG1
      positive patients. Villous height/crypt depth ratio was < 3:1 in 38 of the 60 EMA
      IgG1-positive patients (63.3%), whilst overexpression of ICAM-1 and CD25 was
      observed in all these patients. CONCLUSIONS: In this study, we observed a group
      of CD patients who were EMA IgG1-positive even in the absence of EMA IgA
      positivity and IgA deficiency. The diagnosis was based on the finding of the
      gluten-dependent clinical and histological features typical of CD. Data emerging
      from the present investigation thus suggest that the prevalence of CD should be
      reassessed and that the determination of EMA IgG1 could offer a new tool in the
      diagnostic armamentarium of CD.

PMID- 11240849
TI  - Insulin resistance adds to endothelial dysfunction in hypertensive patients and
      in normotensive offspring of subjects with essential hypertension.
AB  - OBJECTIVES: To evaluate whether endothelium-dependent (nitric oxide-mediated)
      dilation of the brachial artery (BA) is impaired in patients being treated for
      essential hypertension (EH), and whether this abnormality can be detected in
      normotensive offspring of subjects with EH (familial trait, FT); and to
      investigate the interrelationship between flow-mediated vasodilation (FMD) and
      hyperinsulinaemia/insulin resistance. DESIGN: Cross-sectional study. SETTING:
      Angiology department at a teaching hospital. SUBJECTS: The study encompassed 172
      subjects, of whom 46 were treated hypertonics aged 40-55 (49) years, and 44 age
      matched, normotensive volunteers as controls. We also investigated 41 normotonics
      with FT aged 20-30 (25) years and 41 age-and sex-matched controls without FT.
      MAIN OUTCOME MEASURES: Using high-resolution ultrasound, BA diameters at rest,
      during reactive hyperaemia (endothelium-dependent dilation) and after sublingual
      glyceryl trinitrate (GTN) application (endothelium-independent dilation) were
      measured. RESULTS: In hypertonics FMD was significantly lower than in controls
      [2.4 (2.9) vs. 7.4 (2.5)%; P < 0.00005], as was GTN-induced dilation [12.1 (4.3)
      vs. 16.1 (4.6)%; P=0.0007]. In subjects with FT, FMD was also decreased compared
      with the control group [5.8 (4.1) vs. 10.0 (3.0)%; P < 0.00005]. The response to
      GTN was comparable in both groups of young subjects. FMD was negatively related
      to insulin concentration in all subjects studied (P < 0.00005). CONCLUSIONS: In
      treated patients with EH, flow-mediated dilation of the BA as well as endothelium
      independent dilation are decreased. In individuals with FT the endothelial
      function of the peripheral arteries is also altered in the absence of elevated
      blood pressure. Endothelial dysfunction is related to hyperinsulinaemia/insulin
      resistance, which could be one of the pathogenetic determinants of EH and its
      complications.

PMID- 11240850
TI  - Centrifuge polarizing microscope. I. Rationale, design and instrument
      performance.
AB  - We first describe early uses of the centrifuge for deciphering physical
      properties and molecular organization within living cells, as well as the
      development and use of centrifuge microscopes for such studies. The rationale for
      developing a centrifuge microscope that allows high-extinction polarized light
      microscopy to observe dynamic fine structures in living cells is next discussed.
      We then describe a centrifuge polarizing microscope (CPM) that we developed for
      observing fine structural changes in living cells which are being exposed to up
      to approximately 11 500 times earth's gravitational field (g). With the specimen
      housed in a rotor supported on an air spindle motor, and imaged through an
      external microscope illuminated by a precisely synchronized flash of less than 10
      ns duration from a Nd:YAG laser, the image of the spinning object remains steady
      up to the maximum speed of 11 700 rev min-1, or up to approximately 11 500 x g.
      The image is captured, at up to 25 frames s-1, by an interference-fringe-free CCD
      camera that is synchronized to the centrifuge rotor. At all speeds (in 100 rev
      min-1 increments), the image is resolved to better than 1 microm, while
      birefringence of the specimen, housed in a specially designed specimen chamber
      that suffers low-stress birefringence and prevents leakage of the physiological
      solutions, is detected with a retardance sensitivity of better than 1 nm.
      Differential interference contrast and fluorescence images (532 nm excitation) of
      the spinning specimen can also be generated with the CPM. The second part of this
      study (Inoue et al., J. Microsc. 201 (2001) 357-367, describes several biological
      applications of the CPM that we have explored. Individual live cells, such as
      oocytes and blood cells, are supported on a sucrose or Percoll density gradient
      while other cells, such as cultured fibroblasts and Dictyostelium amoebae, are
      observed crawling on glass surfaces. Observations of these cells exposed to the
      high G fields (centripetal acceleration/g) in the CPM are yielding many new
      results that lead to intriguing questions regarding the organization and function
      of fine structures in living cells and related quasi-fluid systems.

PMID- 11240851
TI  - Centrifuge polarizing microscope. II. Sample biological applications.
AB  - The rationale, design and general performance of the CPM (centrifuge polarizing
      microscope) were described in Part I of this study (Inoue et al. J. Microsc. 201
      (2001) 341-356. In this second part, we describe observations on several
      biological samples that we have explored over the past two years using the CPM.
      As described in the first part of the study, although the CPM was basically
      designed as a high-extinction centrifuge polarizing microscope, it also allows
      observations of the specimen exposed to high centrifugal fields up to 10 500 x g
      (earth's gravitational acceleration) in fluorescence (532-nm excitation) and in
      DIC (differential interference or Nomarski contrast).

PMID- 11240852
TI  - High efficiency beam splitter for multifocal multiphoton microscopy.
AB  - In this article we present the development of a multibeam two-photon laser
      scanning microscope. A new type of beam splitter to create the multitude of laser
      beams is described. This type of beam splitter has higher transmission and
      generates more uniform beams than can be achieved with the microlens approach
      used by other groups. No crosstalk exists between the different foci due to small
      temporal delays between the individual beams. The importance of dispersion
      compensation to obtain maximum efficiency of the microscope is discussed. With
      optimum compensation the fluorescence signal was raised by a factor of 14.
      Different modes of detecting the fluorescence signals and their effect on imaging
      speed and resolution are discussed.

PMID- 11240854
TI  - Coaxial scanning near-field optical microscope tips: an alternative for
      conventional tips with high transmission efficiency?
AB  - Since the development of the first scanning near-field optical microscope, great
      effort has been put into the development of near-field optical probe tips with a
      good lateral resolution of the order of several tens of nanometres and a high
      power throughput. Several groups have proposed the use of scanning near-field
      optical tips with a coaxial structure. From electromagnetic theory, it is known
      that such structures have no cut-off frequency and a power transmission close to
      unity. In this paper we discuss some topics concerning the stimulation of optical
      coaxial waves and their propagation behaviour.

PMID- 11240853
TI  - Visualizing filamentous actin on lipid bilayers by atomic force microscopy in
      solution.
AB  - The surface structure of actin filaments (F-actin) was visualized at high
      resolution, by atomic force microscopy (AFM) in aqueous solution, in large
      paracrystals prepared on positively charged lipid monolayers. The increased
      stability of these closely packed specimens allowed us to show that both the long
      pitch (38 nm) and the monomer (5.8 nm) can be directly resolved by AFM in the
      contact mode. The right-handed helical surface, distinguishable in high
      resolution images, was compared with reconstructed models based on electron
      microscopy. The height of the rafts, a measure of the actin filament diameter,
      was 10 +/- 1 nm, whereas the smaller inter-filament distance, 8 +/- 1 nm, was
      consistent with interdigitation of the filaments. The 10 +/- 1 nm F-actin
      diameter is in good agreement with the results of fibre X-ray diffraction. As
      such specimens are relatively easy to prepare without specialized equipment, this
      method may allow the study of the thin filaments in which F-actin-associated
      proteins are also present.

PMID- 11240855
TI  - Quantitative serial sectioning analysis.
AB  - A method for serial sectioning is presented that allows one to take about 20
      sections per hour with spacings in the range 1-20 microm between sections. The
      alignment of the cross-sections is done with a linear variable differential
      transformer; it is thus independent of the microstructure of the sample and does
      not rely upon markers implanted in the sample. The alignment errors as well as
      tilts and rotation errors between sections associated with the new method are
      found to be negligible. Once all the sections are captured in a computer a three
      dimensional image can be constructed. This image can be viewed interactively and
      rotated, thus allowing the direct observation of three-dimensional shapes. It can
      further be used to determine a vast array of microstructural parameters including
      those that cannot be determined from planar sections. The technique is
      illustrated through the reconstruction of the microstructure of a cast standard
      aluminium alloy specimen.

PMID- 11240856
TI  - High resolution protein localization using soft X-ray microscopy.
AB  - Soft X-ray microscopes can be used to examine whole, hydrated cells up to 10
      microm thick and produce images approaching 30 nm resolution. Since cells are
      imaged in the X-ray transmissive "water window", where organic material absorbs
      approximately an order of magnitude more strongly than water, chemical contrast
      enhancement agents are not required to view the distribution of cellular
      structures. Although living specimens cannot be examined, cells can be rapidly
      frozen at a precise moment in time and examined in a cryostage, revealing
      information that most closely approximates that in live cells. In this study, we
      used a transmission X-ray microscope at photon energies just below the oxygen
      edge (lambda = 2.4 nm) to examine rapidly frozen mouse 3T3 cells and obtained
      excellent cellular morphology at better than 50 nm lateral resolution. These
      specimens are extremely stable, enabling multiple exposures with virtually no
      detectable damage to cell structures. We also show that silver-enhanced,
      immunogold labelling can be used to localize both cytoplasmic and nuclear
      proteins in whole, hydrated mammary epithelial cells at better than 50 nm
      resolution. The future use of X-ray tomography, along with improved zone plate
      lenses, will enable collection of better resolution (approaching 30 nm), three
      dimensional information on the distribution of proteins in cells.

PMID- 11240857
TI  - Segmentation of nuclei and cells using membrane related protein markers.
AB  - Segmenting individual cell nuclei from microscope images normally involves volume
      labelling of the nuclei with a DNA stain. However, this method often fails when
      the nuclei are tightly clustered in the tissue, because there is little evidence
      from the images on where the borders of the nuclei are. In this paper we present
      a method which solves this limitation and furthermore enables segmentation of
      whole cells. Instead of using volume stains, we used stains that specifically
      label the surface of nuclei or cells: lamins for the nuclear envelope and alpha-6
      or beta-1 integrins for the cellular surface. The segmentation is performed by
      identifying unique seeds for each nucleus/cell and expanding the boundaries of
      the seeds until they reach the limits of the nucleus/cell, as delimited by the
      lamin or integrin staining, using gradient-curvature flow techniques. We tested
      the algorithm using computer-generated objects to evaluate its robustness against
      noise and applied it to cells in culture and to tissue specimens. In all the
      cases that we present the algorithm gave accurate results.

PMID- 11240859
TI  - Identification and characterization of B-cell epitopes of a 53-kDa outer membrane
      protein from Porphyromonas gingivalis.
AB  - We have previously reported that Porphyromonas gingivalis FDC 381 possesses a 53
      kDa protein antigen (Ag53) on its outer membrane that evokes a strong humoral
      immune response in many patients with periodontal disease and that the humoral
      immune responses to Ag53 differ greatly among patients. To understand how the
      individual humoral immune system against Ag53 was determined, the regions of Ag53
      recognized by specific antibody (B-cell epitopes) and dominant subclasses of
      serum immunoglobulin G (IgG) against major B-cell epitopes were examined by
      enzyme-linked immunosorbent assay. This study used sera from six patients with
      periodontitis, which all reacted strongly with sonic extracts of P. gingivalis
      381 and with purified Ag53, and sera from six periodontally healthy children,
      which did not react with either sonic extracts of P. gingivalis 381 or Ag53. The
      epitopes were identified using synthetic 5-residue overlapping decapeptides
      covering the entire Ag53. Thirteen of 89 synthetic decapeptides showed a strong
      reaction with sera from the periodontal patients, but no reaction with those from
      the healthy children. Four peptides of 13 exerted different immune responses
      among patients. Furthermore, restriction analyses of the highly antigenic regions
      revealed that three sequences, RAAIRAS, YYLQ and MSPARR, were identified as major
      B-cell epitopes. Additionally, these epitopes were recognized mainly by the IgG2
      isotype. These data suggest that the difference of B-cell epitopes might
      influence individual differences in antibody titer against Ag53 and also that the
      epitopes recognized commonly by multiple antibodies are quite valuable for
      peptide vaccine development against P. gingivalis infection.

PMID- 11240858
TI  - Production of inflammatory cytokines by human gingival fibroblasts stimulated by
      cell-surface preparations of Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis is a gram-negative rod associated with the progression
      of human periodontal disease. Inflammatory cytokines are believed to be the major
      pathological mediators in periodontal diseases. We therefore investigated the
      productions of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-8
      (IL-8), and tumor necrosis factor-alpha (TNF-alpha) in human gingival fibroblasts
      treated with lipopolysaccharide, polysaccharide and outer-membrane proteins from
      P. gingivalis ATCC 53977. Outer-membrane protein from P. gingivalis enhanced the
      production of IL-6 and IL-8 from the cells of periodontium in vitro as well as
      lipopolysaccharide did. The IL-8 production activity of polysaccharide from P.
      gingivalis was higher than that of other cell-surface components. The levels of
      IL-6 and IL-8 released from the P. gingivalis lipopolysaccharide-treated human
      gingival fibroblasts were lower than those of the same cells treated with
      lipopolysaccharides from Actinobacillus actinomycetemcomitans or Escherichia
      coli. Rabbit antisera against either outer-membrane protein or lipopolysaccharide
      inhibited the IL-6 and IL-8 production derived from human gingival fibroblasts
      stimulated sonicated supernatants from P. gingivalis. The present study suggests
      that, in addition to lipopolysaccharide, outer-membrane protein and
      polysaccharide of P. gingivalis are also pathological mediators in periodontal
      diseases.

PMID- 11240860
TI  - Acquisition of iron from human transferrin by Porphyromonas gingivalis: a role
      for Arg- and Lys-gingipain activities.
AB  - Porphyromonas gingivalis, a key causative agent of adult periodontitis, is known
      to produce a variety of virulence factors including proteases. The aim of this
      study was to evaluate the participation of Arg- and Lys-gingipain activities of
      P. gingivalis in the acquisition of iron from human transferrin and its
      subsequent utilization in growth. Iron-saturated transferrin was found to support
      the long-term growth of P. gingivalis. Our results indicated that P. gingivalis
      does not produce siderophore and does not possess ferric reductase and
      transferrin-binding activities. Incubating transferrin with P. gingivalis
      resulted in degradation of the protein, a step that may be critical for the
      acquisition of iron from transferrin. Spontaneous and site-directed mutants of P.
      gingivalis deficient in one or several proteases were used to demonstrate the key
      role of specific enzymes in degradation of transferrin and subsequent utilization
      for growth. The lack of both Arg- and Lys-gingipain activities (mutants M1 and
      KDP128) was associated with an absence of degradation of transferrin and the
      incapacity of bacteria to grow in the presence of transferrin as the sole source
      of iron. It was also found that the Lys-gingipain activity is more critical than
      the Arg-gingipain activity since the mutant KDP112 (deficient in Arg-gingipain A
      and B) could grow whereas the mutant KDP129 (deficient in Lys-gingipain) could
      not. The fact that growth of mutant KDP112 was associated with a lower final
      optical density and a generation time much longer compared with the parent strain
      suggests that the Arg-gingipain activity also participates in the acquisition of
      iron from transferrin. Selected inhibitors of cysteine proteases (TLCK, leupeptin
      and cathepsin B inhibitor II) were tested for their capacity to reduce or inhibit
      the growth of P. gingivalis under different iron conditions. All three inhibitors
      were found to completely inhibit growth of strain ATCC 33277 in a medium
      supplemented with transferrin as the source of iron. The inhibitors had no
      effects when the bacteria were grown in a medium containing hemin instead of
      transferrin. The ability of P. gingivalis to cleave transferrin may be an
      important mechanism for the acquisition of iron from this protein during
      periodontitis.

PMID- 11240861
TI  - Binding of oral streptococci to human fibrinogen.
AB  - The interaction of oral streptococci with human fibrinogen was investigated.
      Streptococcus gordonii was chosen as a representative species to study the
      binding to fibrinogen. S. gordonii DL1 adhered to immobilized fibrinogen and
      bovine serum albumin. Binding to immobilized fibrinogen was saturable,
      concentration and temperature dependent. The binding of S. gordonii DL1 to
      fibrinogen was inhibited by anti-fibrinogen antibody. Heating of the bacteria for
      1 h at 95 degrees C resulted in 90% inhibition of the binding. Trypsin treatment
      of the bacteria resulted in decreased binding. Neither lipoteichoic acid nor
      culturing of the bacteria in a sucrose-supplemented medium had any effect on the
      binding. S. gordonii, Streptococcus sanguinis, Streptococcus mitis, and
      Streptococcus oralis bound to the immobilized fibrinogen, but mutans streptococci
      did not. None of the oral streptococci tested bound to the fibrinogen in fluid
      phase. These results suggest that the binding of S. gordonii DL1 to immobilized
      fibrinogen is mediated through a specific protein adhesin-receptor interaction,
      and fibrinogen acts as a cryptitope.

PMID- 11240862
TI  - Inhibitory effect of sorbitol on sugar metabolism of Streptococcus mutans in
      vitro and on acid production in dental plaque in vivo.
AB  - This study was conducted to find out whether sorbitol inhibits the sugar
      metabolism of Streptococcus mutans in vitro and the acid production in dental
      plaque in vivo. S. mutans NCIB 11723 was anaerobically grown in sorbitol
      containing medium. The rate of acid production from sugars was estimated with a
      pH stat. The rate of acid production from glucose or sucrose was not changed at
      various concentrations of oxygen. By the addition of sorbitol to sugar, however,
      the acid production was decreased with increasing levels of oxygen. Intracellular
      NADH/NAD+ ratio and (dihydroxyacetone-phosphate+glyceraldehyde-phosphate)/3
      phosphoglycerate ratio were high whenever the acid production was inhibited by
      sorbitol. Sorbitol also inhibited the acid production in dental plaque in vivo.
      These results suggest that the increased NADH/NAD+ ratio during sorbitol
      metabolism through the inactivation of pyruvate formate-lyase by oxygen inhibited
      glyceraldehyde-phosphate dehydrogenase and then the acid production of S. mutans
      and the one in dental plaque.

PMID- 11240863
TI  - Microorganisms isolated from root canals presenting necrotic pulp and their drug
      susceptibility in vitro.
AB  - The knowledge about causative agents involved in endodontic infections is
      increasing, especially due to the improvement of culture techniques for anaerobic
      bacteria, showing that these microorganisms are predominant in this pathology. In
      this study, 31 canals with pulp necrosis were microbiologically analyzed before
      and after manipulation. Obligate and facultative anaerobes, microaerophilic
      bacteria and yeasts were recovered from 24, 14, 5 and 2 clinical specimens,
      respectively. The most frequent genera were Prevotella, Fusobacterium,
      Lactobacillus, Streptococcus, Clostridium and Peptostreptococcus for bacteria and
      Candida and Saccharomyces for yeasts. Strong positive associations, using an odds
      ratio system, were found between Clostridium and Prevotella and between
      Peptostreptococcus and Fusobacterium. Even after the instrumentation and the use
      of Ca(OH)2, facultative anaerobes were detected in two root canals and yeasts in
      three. Microorganisms were isolated from seven canals at the end of the
      endodontic treatment: facultative anaerobes from five and yeasts from one. The
      microbiological evaluation of root canals with pulp necrosis suggests the
      presence of polymicrobial infections, mainly involving obligate anaerobes, and
      shows that the infection may persist after treatment.

PMID- 11240864
TI  - Phenotypes and randomly amplified polymorphic DNA profiles of Candida albicans
      isolates from root canal infections in a Finnish population.
AB  - A total of thirty-seven Candida albicans isolates from root canal infections in a
      Finnish population were subtyped using phenotypic and genotypic methods. A
      previously described biotyping method based on the presence of five different
      enzymes, assimilation of eleven different carbohydrates and boric acid
      sensitivity of the yeasts was used to determine the phenotype. Commercially
      available API ZYM and API 20 C test kits were used to determine the presence of
      enzymes and assimilation of carbohydrates. The sensitivity of the isolates to
      boric acid was tested by their ability to grow on yeast-nitrogen-agar with
      incorporated boric acid (1.8 mg. ml(-1)). Combination of the tests revealed a
      total of 14 different phenotypes. The majority of the isolates, 26 strains, were
      classifiable into three major phenotypes: 16 isolates (43.2%) belonged to
      phenotype A1R, six (16.2%) to A1S and four (10.8%) to B1S. The remaining 11
      phenotypes represented only a single isolate each. The randomly amplified
      polymorphic DNA profiles were used to determine the genotypes. For this purpose
      two different primers, RSD6 and RSD12 were used to develop a combination randomly
      amplified polymorphic DNA profile for each isolate. Altogether 31 genotypes were
      noted among the 37 isolates, of which only three pairs of isolates presented with
      congruent phenotypic and genotypic profiles. The heterogeneity of both the
      phenotypic and randomly amplified polymorphic DNA profiles of C. albicans
      isolates from root canal infections is akin to previous reports from other oral
      and non-oral sources in different geographic locales.

PMID- 11240865
TI  - Subgingival strains of Candida albicans in relation to geographical origin and
      occurrence of periodontal pathogenic bacteria.
AB  - Clonal diversity of subgingival yeast strains was determined in relation to
      geographical location and coexistence of selected periodontal pathogenic
      bacteria. A total of 60 dental patients from Finland, the United States and
      Turkey each contributed five Candida albicans isolates. C. albicans isolates were
      serotyped using slide agglutination and genotyped using polymerase chain reaction
      (PCR) amplification and a random sequence primer. In general, each study subject
      yielded C. albicans isolates belonging to the same serotype and genotype. C.
      albicans serotype A occurred more frequently in subjects from Finland and Turkey
      than in subjects from the United States. A total of 27 PCR-based C. albicans
      genotypes were identified. One C. albicans genotype occurred with particularly
      high frequency in subjects from Turkey and another genotype in subjects from the
      United States. Relationships were identified between C. albicans serotypes and
      genotypes. Further studies are needed to determine environmental factors of
      importance for subgingival colonization and persistence of C. albicans.

PMID- 11240866
TI  - Salivary calprotectin levels are raised in patients with oral candidiasis or
      Sjogren's syndrome but decreased by HIV infection.
AB  - Calprotectin levels were determined in whole saliva from patients predisposed to
      oral candidiasis due to HIV infection or Sjogren's syndrome and from patients
      with candidiasis associated with various oral disorders (e.g. lichen planus, oral
      ulceration). Mean calprotectin levels were higher in whole saliva (2
      microgram/ml) than in parotid saliva (0.3 microgram/ml). Oral candidiasis was
      associated with raised whole saliva calprotectin levels in all groups studied.
      HIV infection was associated with lower levels of salivary calprotectin, in the
      presence of high or low salivary Candida counts, although CD4+ lymphocyte counts
      did not significantly correlate with calprotectin concentrations. Calprotectin
      levels were elevated in saliva from Sjogren's syndrome patients with oral
      candidiasis, consistent with mucosal transudation of calprotectin from inflamed
      mucosa and limited dilution due to decreased salivary flow rates. This study
      indicates that oral candidiasis is associated with raised calprotectin levels
      secondary to mucosal inflammation, but that diminution of this candidacidal
      factor due to HIV infection may be a predisposing factor in the aetiology of oral
      candidiasis.

PMID- 11240867
TI  - Altered antigenicity in periodontitis patients and decreased adhesion of
      Porphyromonas gingivalis by environmental temperature stress.
AB  - Periodontopathogenic bacteria survive various environmental changes during the
      progression of periodontal disease. Alterations in metabolism and protein
      expression will have to take place to adapt their physiological functions to
      environmental stress. We examined the effects of an elevation of 2 degrees C in
      temperature on the adhesive ability and antigenicity of Porphyromonas gingivalis.
      Elevation of growth temperature of P. gingivalis from 37 degrees C to 39 degrees
      C remarkably suppressed the expression of surface filamentous structures, such as
      fimbriae, as well as the adhesive capacities to salivary components and
      Streptococcus oralis. Sera of severe periodontitis patients revealed a marked
      increase in serological activity with 39 degrees C cells than with 37 degrees C
      cells. The alteration of protein profiles of bacterial surface components by
      temperature elevation was demonstrated by SDS-PAGE, and their Western blot
      profiles were also different from those of cells grown at 37 degrees C. Although
      a uniform trend was not found in the altered patterns, sera from severe
      periodontitis patients detected more antigenic proteins in cells grown at 39
      degrees C than 37 degrees C cells. These observations suggest that P. gingivalis
      downregulates the expression of fimbriae and alters its adhesive capacity and
      antigenicity by the temperature stress that could occur during the disease
      progression.

PMID- 11240868
TI  - Improved viability of the low birth weight infant and the increasing needs for
      anaesthesia.

PMID- 11240869
TI  - Should we reconsider awake neonatal intubation? A review of the evidence and
      treatment strategies.

PMID- 11240870
TI  - Aspiration and regurgitation prophylaxis in paediatric anaesthesia.
AB  - BACKGROUND: Surveys of aspiration prophylaxis in paediatric anaesthesia do not
      exist. METHODS: A postal survey was sent out to all UK members of the Association
      of Paediatric Anaesthetists (APA) to assess current practice. We asked about
      minimum fasting times for liquids and solids/milk, their routine acid aspiration
      prophylaxis and perceived risk factors for emergency and elective surgery in
      children those less than 1 year old and those aged 1-14 years. We also asked if
      the APA member had more than 10 years experience in paediatric anaesthesia.
      RESULTS: One hundred and two (55.1%) APA members replied out of a total of 185
      questionnaires sent. Eighty-eight (88/102) were considered valid. Fasting in
      emergencies is approximately 4 h for solids/milk and 2 h for clear liquids.
      Fasting for elective surgery is between 5 and 6 h for solids/milk and 2 h for
      clear liquids. Pharmacological methods to reduce the risk of aspiration are not
      used. Mechanical methods vary from 40-50% for cricoid pressure and 20-30% for
      nasogastric aspiration if a tube is present. The presence of a hiatus hernia is
      perceived by over 80% as a risk factor, previous aspiration by over 60%,
      difficult intubation, cerebral palsy and sepsis by 20-30%. CONCLUSION: Perceived
      risk factors vary with "experience": hiatus hernia, difficult intubation and
      cerebral palsy are less important whereas previous aspiration and renal failure
      appear to be more important for paediatric anaesthetists with less than 10 years
      in paediatric anaesthetic practice.

PMID- 11240871
TI  - Effects of i.v. metoclopramide, atropine and their combination on gastric
      insufflation in children anaesthetized with sevoflurane and nitrous oxide.
AB  - METHODS: To determine effects of i.v. metoclopramide, atropine and their
      combination on the airway pressures at which gastric insufflation occurs in
      children, 45 healthy infants and children (ASA I) received an inhalational
      induction of anaesthesia with sevoflurane, N2O and O2. A blinded observer used a
      stethoscope to auscultate over the upper abdomen for any air entry. First,
      proximal airway pressure was slowly increased by closing the pop-off valve of the
      anaesthesia machine until gas was heard entering the stomach (pop-off point,
      control measurement). If the peak inspiratory pressure reached 40 cm H2O, the
      patient was to be excluded from the study. Then, all subjects randomly received
      i.v. atropine 0.01 mg.kg-1, metoclopramide 0.2 mg.kg-1, or atropine 0.01 mg.kg-1
      plus metoclopramide 0.2 mg.kg-1 (n=15 each), and determination of the pop-off
      point was repeated 5 min later. The stomach was evacuated before each
      measurement. RESULTS: Atropine significantly decreased the pop-off point [from 21
      +/- 3 to 19 +/- 2 cm H2O (mean +/- SD), P < 0.05], while metoclopramide
      significantly increased the pop-off point (from 20 +/- 3 to 26 +/- 6 cm H2O, P <
      0.05). The combination of metoclopramide and atropine did not alter the pop-off
      point (from 20 +/- 2 to 19 +/- 5 cm H2O). CONCLUSION: Since metoclopramide exerts
      only mild effect on the pop-off point, cricoid pressure still remains the
      standard anaesthetic practice to prevent gastric insufflation in children.
      Prophylactic i.v. metoclopramide may be restricted to, and its clinical
      usefulness should be determined in, symptomatic patients with gastro-oesophageal
      reflux.

PMID- 11240872
TI  - A comparison of the respiratory effects of high concentrations of halothane and
      sevoflurane.
AB  - We studied the respiratory effects of the administration of either 5% halothane
      or 8% sevoflurane in 70% nitrous oxide (N2O) for 5 min in 21 boys aged 1-5 years.
      A similar degree of ventilatory depression was noted with both agents. Minute
      volume fell by approximately 50% as a result of a reduction in tidal volume
      despite an increase in respiratory rate.

PMID- 11240873
TI  - Safety and efficacy of peribulbar block as adjunct to general anaesthesia for
      paediatric ophthalmic surgery.
AB  - METHODS: Fifty children (age 5-14 years, ASA I-II) undergoing elective ophthalmic
      surgery were chosen for the study. Of these, 25 received intravenous pethidine
      (control group) and 25 received a peribulbar block (block group) for
      perioperative analgesia, and were monitored intraoperatively and postoperatively
      by an investigator blinded to the analgesic technique. RESULTS: Intraoperative
      values of haemodynamic variables were significantly higher in the control group
      (P < 0.01). Requirement for intraoperative rescue analgesic and postoperative
      analgesia was higher in the control group (P < 0.05 and P < 0.001, respectively).
      Children in the block group had lower postoperative pain scores at all times.
      Incidence of oculocardiac reflex was significantly higher (P < 0.001) in the
      control group. Seventy-six percent of children in the control group had
      postoperative nausea and vomiting compared to 20% children in the block group (P
      < 0.001). CONCLUSION: There were no complications related to the block.
      Peribulbar block appears to be a safe and useful analgesic technique for
      paediatric ophthalmic surgery.

PMID- 11240874
TI  - Acid-base, electrolyte and metabolite concentrations in packed red blood cells
      for major transfusion in infants.
AB  - METHODS: Acid-base, electrolyte and metabolite concentrations were determined in
      100 U of packed red blood cells (RBC) preserved in extended-storage media to be
      used for major transfusion in paediatric and cardiac surgery. RESULTS: In fresh
      RBC, low pH, bicarbonate (cHCO3-), base excess (BE) and high glucose values were
      observed all outside the physiological range. With lengthening storage duration,
      values of pH, cHCO3-, BE, sodium and glucose decreased and carbon dioxide,
      potassium and lactic acid concentrations increased [mean +/- SD (range): storage
      duration 6.7 +/- 3.8 (1-17) days, pH 6.79 +/- 0.1 (6.53-6.99); mmol.l-1: cHCO3-
      11.1 +/- 1.5 (6.2-14.5), BE - 29.2 +/- 4.1 ([-39.4] - [-20.9]), potassium 20.5 +/
      7.8 (4.2-43.6), glucose 24.1 +/- 6.1 (16.7-29.2), lactic acid 9.4 +/- 4 (4.3
      21.4)]. CONCLUSION: Massive and rapid transfusion of RBC may lead to a severe
      burden of hydrogen ions, carbon dioxide, potassium, glucose and lactic acid and
      this can be avoided by cell saver blood processing, when autologous erythrocytes
      from the operative field are saved and substrate load and storage lesions from
      packed red blood cells are minimized in one step by washing.

PMID- 11240875
TI  - Use of impedance cardiography to monitor haemodynamic changes during laparoscopy
      in children.
AB  - METHODS: Haemodynamic changes were measured noninvasively using impedance
      cardiography (ICG) in 30 ASA I children during laparoscopic varicocelectomy under
      general anaesthesia. After induction and intubation, mechanical ventilation was
      started, then pneumoperitoneum (PP) was created. During the course of
      anaesthesia, values of endtidal CO2 pressue (PECO2), peak inspiratory airway
      pressure (PIP), heart rate (HR), mean arterial blood pressure (MABP), stroke
      volume index (SVI), cardiac index (CI) and systemic vascular resistance index
      (SVRI) were recorded at 1 min intervals. We analysed four periods: T1, before
      induction; T2, after induction; T3, during PP; T4, after desufflation of PP until
      awake. RESULTS: After induction of anaesthesia a significant reduction of HR,
      MABP and CI was recorded. Creating PP together with the use of a 15 degrees head
      down tilt resulted in a further drop in CI, mainly caused by the reduction of
      SVI, and an elevation of MABP and SVRI. We measured a 25% total decrease of CI.
      CONCLUSION: Our patients tolerated this significant reduction of cardiac output
      well. We have demonstrated that ICG can be used to track the haemodynamic changes
      caused by PP in children, and suggest that this type of monitoring is useful in
      this group of age during laparoscopy.

PMID- 11240876
TI  - Anaesthetic technique for transoesophageal echocardiography in children.
AB  - OBJECTIVE: To document the safety and efficacy of an anaesthetic technique in
      paediatric patients undergoing transoesophageal echocardiography (TOE). METHODS:
      Prospective descriptive study performed in a children's hospital with all
      patients undergoing TOE. Topical analgesia of the pharynx was achieved with
      lidocaine. Anaesthesia was induced with midazolam (25 microg.kg-1), fentanyl (1
      microg.kg-1), and propofol (0.5-1 mg.kg-1), followed by a continuous infusion of
      propofol (5-10 mg.kg-1.h-1). RESULTS: Thirty patients are reported. The mean age
      was 11.4 +/- 5.1 years (range 1-22) and weight 40.5 +/- 22.1 kg (range 10-110).
      All the patients tolerated the procedure well. Two patients experienced brief
      oxygen desaturations during induction, 10 patients coughed during the procedure,
      and six patients had significant muscle activity requiring supplemental doses of
      propofol. None of the patients experienced nausea or vomiting. CONCLUSION: We
      conclude that our anaesthetic technique in spontaneously breathing paediatric
      patients during TOE is effective and appears to be safe in children with heart
      disease.

PMID- 11240877
TI  - Comparison of spontaneous with controlled mode of ventilation in tonsillectomy.
AB  - METHODS: This randomized study compares spontaneous versus controlled ventilation
      in 60 ASA I and II patients undergoing tonsillectomy as regards haemodynamic
      stability, recovery characteristics, intra- and immediate postoperative
      complications and surgical impressions. RESULTS: The patients in the balanced
      anaesthesia (B) group showed less haemodynamic variability compared to baseline
      after tracheal intubation, mouth gag application and removal and incision. Two
      patients had dysrhythmias in the B group compared to six in the spontaneous
      breathing (S) group. Six patients in the S group had a rise in endtidal carbon
      dioxide concentration above 7.8 kPa (60 mmHg). Recovery scores were higher in the
      B group at 10 and 20 min into recovery. The surgical impression of bleeding and
      jaw relaxation was similar with both groups. The incidence of postoperative
      nausea and vomiting and agitation was higher in the S group but did not achieve
      statistical significance. CONCLUSION: Use of balanced anaesthesia offered more
      haemodynamic stability and a rapid recovery.

PMID- 11240878
TI  - Monitoring of pacemaker induced changes in cardiac output with inspired to
      endtidal oxygen difference in paediatric cardiac surgery patients.
AB  - METHODS: Fourteen children aged 4-15 months were studied after corrective cardiac
      surgery. Heart rate was increased by 20% with an external pacemaker. Cardiac
      output (CO) was measured with thermodilution. Oxygen saturation was measured in
      systemic artery (SaO2), central vein (ScvcO2) and pulmonary artery (SvO2).
      Inspiratory to endtidal oxygen difference (FI-ETO2) was measured using a
      paramagnetic technique. SvO2 was measured continuously using a spectrophotometric
      technique. RESULTS: CO increased in three patients and decreased in 11 patients
      during pacing. Regression between DeltaCO and Delta(1/Sa-vO2), Delta(FI-ETO2/Sa
      vO2), Delta(FI-ETO2/Sa-cvcO2) showed r=0.70, r=0.76 and r=0.75, respectively.
      DeltaCO exceeded 10% in 17 of 26 interventions. Changes in FI-ETO2 of equal
      direction as changes in CO occurred in 12 of these 17 interventions. CONCLUSION:
      Estimations of CO changes, based on SvO2, can be enhanced if changes in FI-ETO2
      are also measured. ScvcO2 instead of SvO2 gives equivalent results. Sudden
      changes in FI-ETO2 after pacemaker initiation or termination can predict the
      direction of CO changes.

PMID- 11240879
TI  - A dual epidural catheter technique to provide analgesia following posterior
      spinal fusion for scoliosis in children and adolescents.
AB  - BACKGROUND: The authors report their experience with the use of a dual epidural
      catheter technique in controlling pain following long posterior spinal fusion and
      instrumentation for scoliosis in children and adolescents. METHODS: Following
      completion of the surgical procedure and prior to wound closure, the upper
      catheter was inserted with the tip directed cephalad to T1-4 while the tip of the
      lower catheter was positioned at the L1-4 level. As the surgical wound was being
      closed, the catheters were dosed with fentanyl and hydromorphone followed by a
      continuous infusion of ropivacaine plus hydromorphone. Postoperative pain was
      assessed every 2-4 h using a visual analogue score or an observational
      behavioural score (0=no pain, 10=worst imaginable pain). There were 14 patients
      ranging in age from 5-17 years (12.7 +/- 3.5) and in weight from 19-68 kg (44.3
      +/- 17.5). The epidural catheters were left in place until the fifth
      postoperative day. RESULTS: The mean of the median pain score from each patient
      was 1.5 +/- 1.6, 1.6 +/- 1.5, 1.4 +/- 1.3, 1.1 +/- 1.1 and 0.9 +/- 0.9,
      respectively, on postoperative days 1 through 5. The mean of the maximum pain
      scores was 3.5 +/- 2.3 (range 0-7), 4 +/- 1.6 (range 2-6), 3.1 +/- 1.7 (range 1
      6), 2.4 +/- 1.5 (range 0-4) and 2.2 +/- 1.4 (range 0-4), respectively, on
      postoperative days 1 through 5. CONCLUSION: No adverse effects related to
      epidural analgesia were noted.

PMID- 11240880
TI  - Pharmacokinetics of oral diclofenac and acetaminophen in children after surgery.
AB  - BACKGROUND: Our aim was to study the pharmacokinetics and pain scores following
      administration of single oral doses of either diclofenac or high-dose
      acetaminophen (paracetamol). METHODS: In the morning, the day after
      tonsillectomy, children 5-15 years of age were randomized in a double-blind
      manner to receive either diclofenac 1-2 mg.kg-1 (n=11) or acetaminophen 22.5
      mg.kg-1 (n=10). Postoperative pain was assessed by self-report and blood samples
      were drawn every 30 min for 4 h after medication. RESULTS: Large interindividual
      differences in maximum plasma diclofenac concentrations (Cmax) were found. Mean
      Cmax was 2.4+/-1.3 microg.ml-1 and mean tmax was 2+/-0.5 h. No significant
      reduction in pain score with diclofenac was seen at any of the assessments during
      the study period. Eight of 10 children achieved Cmax of acetaminophen within the
      10-20 microg.ml-1 antipyretic range. Mean tabs was 0.7+/-0.3 h and mean Cmax and
      tmax were 12.7+/-3.8 microg ml-1 and 1.4+/-0.5 h, respectively. No significant
      reduction in pain score with acetaminophen was seen at any of the assessments
      during the study period. CONCLUSIONS: The achieved concentrations of diclofenac
      and acetaminophen were not able to significantly reduce the children's pain score
      during the 5 h postingestion study period. Analgesic plasma acetaminophen
      concentrations may be higher than those required for antipyresis.

PMID- 11240882
TI  - Historical abstract: Gas inductions.

PMID- 11240881
TI  - A randomized controlled trial of the antiemetic effect of three doses of
      ondansetron after strabismus surgery in children.
AB  - METHODS: One hundred and thirty-one healthy children, aged 31-152 months,
      undergoing strabismus surgery under general anaesthesia, were randomly allocated
      to one of four groups: group A received 0.04 mg.kg-1 ( identical with 1 mg.m-2)
      of ondansetron, group B 0.1 mg.kg-1 ( identical with 2.5 mg.m-2), group C 0.2
      mg.kg-1 ( identical with 5 mg.m-2) and group D placebo, given intravenously
      following induction of anaesthesia. Morphine 0.15 mg.kg-1 was given
      intravenously, intraoperatively, to provide postoperative analgesia. Hourly
      records of emetic episodes were made for 24 h. RESULTS: A considerably higher
      proportion of children suffered emesis in the placebo group compared to the
      active treatment groups taken together, during the first 8 h of postoperative
      care (76% vs. 45%, P=0.002). During the first 8 h, only 25% of those in treatment
      group C suffered emesis, the number-needed-to-treat was 3. There was a
      statistically significant decrease in the chance of vomiting with increasing dose
      of ondansetron (P=0.03). By 24 h, the difference in the rate of emesis was less
      marked but still statistically significant (90% vs. 69%, P=0.03). CONCLUSION:
      Overall, children given ondansetron had less than one-half the risk of vomiting
      compared to those given placebo (hazard ratio 0.46, 95% confidence interval 0.29
      0.74). The mean number of emetic episodes declined from 2.73 in the placebo group
      to 1.92 in treatment group C. There was no difference in the incidence of side
      effects between groups.

PMID- 11240883
TI  - Anaesthetic management for a patient with Dejerine-Sottas disease and asthma.
AB  - Dejerine-Sottas disease is a very uncommon degenerative disease of the peripheral
      nervous system. The details of perioperative anaesthetic management are discussed
      including the use of epidural anaesthesia, with supplemental intravenous
      anaesthesia and an LMA.

PMID- 11240884
TI  - Perioperative considerations in a hypothyroid infant with hepatic haemangioma.
AB  - Hepatic haemangiomas in infants are rare. An infant with both a hepatic
      haemangioma and a severe hypothyroid condition, unresponsive to conventional
      thyroxine therapy, will be described. This case presented here is the
      perioperative management of a critically ill infant who had myocardial depression
      secondary to hypothyroidism and a hepatic haemangioma that required embolization.
      To our knowledge, this is the first published report describing intravenous
      triiodothyronine as a therapeutic modality to stabilize a hypothyroid infant
      prior to undergoing a general anaesthetic.

PMID- 11240885
TI  - Tumour lysis syndrome during anaesthesia.
AB  - We describe a child who developed acidosis, hyperkalaemia and cyanosis while
      emerging from an otherwise uneventful anaesthetic. A diagnosis of tumour lysis
      syndrome was suspected and confirmed biochemically. Although this syndrome is
      usually associated with chemotherapy and has been described to occur
      spontaneously, it has not previously been reported as being associated with
      anaesthesia.

PMID- 11240886
TI  - A review of anaesthetic technique in 15 paediatric patients with
      temporomandibular joint ankylosis.
AB  - Temporomandibular joint ankylosis presents a serious problem for airway
      management. This relatively rare problem becomes even more difficult to manage in
      children because of their smaller mouth opening with near total trismus, and the
      need for general anaesthesia before making any attempts to secure the airway. A
      technique for securing the airway that combines local blocks for nerves of larynx
      and topical anaesthesia of upper airways for placement of these blocks, and
      minimal general anaesthesia for these manoeuvres, is described. For general
      anaesthesia, a combination of halothane and ether by spontaneous ventilation,
      using bilateral nasopharyngeal airways, was used. Because of the severe trismus,
      a tongue depressor or tip of a laryngoscope was used with a fibreoptic light
      source in the buccal sulcus to visualize the tracheal tube in the pharynx. Nasal
      forceps, with a smaller tip and narrower blade than Magill forceps was used to
      guide the tracheal tube towards the air bubbles coming out of larynx. No attempt
      was made to visualize the larynx, but its position was guessed from the direction
      of these air bubbles. We review the anaesthetic technique in 15 such cases of
      severe trismus managed successfully between 1986 and 1999.

PMID- 11240887
TI  - Use of the Bispectral Index monitor to aid titration of propofol during a drug
      assisted interview.
AB  - We report two drug-assisted interviews with propofol in an 18-year-old with the
      diagnosis of Complex Regional Pain Syndrome type 1. We describe difficulty in
      titration of propofol in the first interview. Consequently, in the second
      interview, the Bispectral Index (BIS) monitor was applied to assist adjustment of
      the propofol infusion. This facilitated the achievement of a prolonged sedative
      hypnotic state for a successful neuropsychological evaluation. Pertinent
      information was obtained from this patient. However, the role of drug-assisted
      interviews as a technique needs to be further elucidated.

PMID- 11240888
TI  - Halothane: the last word?

PMID- 11240890
TI  - Halothane: the last word?

PMID- 11240891
TI  - Intravenous anaesthesia with remifentanil in a preterm infant.

PMID- 11240892
TI  - Continuous epidural infusion: human vigilance is essential.

PMID- 11240893
TI  - Anaesthetists and perioperative risk.

PMID- 11240894
TI  - The Bair that did not hug.

PMID- 11240896
TI  - Do maternally acquired antibodies protect infants from malaria infection?
AB  - Neonates and infants are relatively protected from clinical malaria, but the
      mechanism of this protection is not well understood. Maternally derived
      antibodies are commonly believed to provide protection against many infectious
      diseases, including malaria, for periods of up to 6-9 months but several recent
      epidemiological studies have produced conflicting results regarding a protective
      role of passively acquired antimalarial antibodies. In this article, we review
      the epidemiological evidence for resistance of young infants to malaria,
      summarize the data on antimalarial antibody levels and specificity and their
      association with protection from malaria infection or clinical disease, and
      explore alternative explanations for resistance to malaria in infants.

PMID- 11240897
TI  - Th2 polarization of the immune response of BALB/c mice to Ixodes ricinus instars,
      importance of several antigens in activation of specific Th2 subpopulations.
AB  - BALB/c mice were infested with Ixodes ricinus larvae, nymphs or adults.
      Expression of IL-4 and IFN-gamma mRNA in axillary and brachial draining lymph
      node cells were measured by competitive quantitative reverse transcription
      polymerase chain reaction 9 days after the beginning of primary-infestation. IL-4
      mRNA was always higher than that of IFN-gamma mRNA for all tick instars.
      Moreover, IL-4 mRNA expression progressively increased during nymphal primary
      infestation with a high burst of expression 7 days after the beginning of
      infestation. No evolution of IFN-gamma mRNA expression was detected. Draining
      lymph node cells of infested BALB/c produced higher level of IL-4 than IFN-gamma
      following in vitro restimulation with adult tick saliva, salivary gland extract
      (SGE) or with five selected different chromatographic fractions of SGE. Anti-tick
      IgG1 antibodies but no IgG2a were detected in BALB/c pluri-infested with I.
      ricinus nymphs, which confirmed the Th2 polarization of the immune response.

PMID- 11240898
TI  - Alterations of intralesional and lymph node gene expression and cellular
      composition induced by IL-12 administration during leishmaniasis.
AB  - Changes in gene expression and cellular distribution in the lymph node and at the
      site of infection, the footpad, during Leishmania major infection and/or IL-12
      administration were evaluated. Otherwise susceptible BALB/c mice given IL-12 are
      able to resolve infection. Interestingly, iNOS was not induced in the lymph node
      by IL-12, yet, nitric oxide is critical in the control of leishmaniasis. However,
      we observed an increase in iNOS at the lesion site in response to IL-12. These
      results reflect the importance of examining the primary site of infection. We
      observed no changes in inflammation at the lesion site; however, IL-12 promoted
      an early inflammatory response in the lymph nodes. IL-12 administration
      differentially affected both the local and systemic immune response to invading
      leishmanial parasites. IL-12 induced iNOS at the lesion site and an early
      granulomatous inflammation in the lymph node; therefore, we hypothesize that
      these are key events responsible for the resolution of disease in BALB/c mice
      treated with IL-12.

PMID- 11240899
TI  - Immunity to experimental neosporosis in pregnant sheep.
AB  - Neospora caninum is an important cause of fetal loss in cattle but has also
      infrequently been shown to cause disease in sheep and goats. Experimental
      infection of pregnant sheep with N. caninum causes clinical and pathological
      changes very similar to those of neosporosis in cattle. An experiment in sheep
      was undertaken to examine whether infection with N. caninum before pregnancy
      conferred immunity to subsequent challenge with the parasite during pregnancy.
      Primary inoculation of NC1 tachyzoites subcutaneously, either before or during
      pregnancy, caused a significant temperature response in ewes, while those given a
      secondary challenge at 90 days gestation (dg) did not show such a response.
      Primary infection of 12 ewes during pregnancy resulted in the loss of all fetuses
      while a further 12 ewes inoculated with NC1 tachyzoites before mating and
      subsequently challenged with the same dose at 90 dg produced nine live and seven
      dead lambs. There were no fetal deaths in ewes only infected with Neospora before
      mating although there was serological evidence of vertical transmission in four
      of their clinically normal offspring while Neospora DNA was detected in the
      cerebrospinal fluid of a fifth healthy lamb. Thus an experimental primary
      infection with N. caninum during pregnancy killed all the fetuses while
      inoculation before pregnancy did not cause any mortality but did provide a degree
      of protection against subsequent challenge with Neospora during pregnancy.

PMID- 11240900
TI  - A heart-specific CD4+ T-cell line obtained from a chronic chagasic mouse induces
      carditis in heart-immunized mice and rejection of normal heart transplants in the
      absence of Trypanosoma cruzi.
AB  - To study the role of autoreactive T cells in the pathogenesis of cardiomyopathy
      in Chagas' disease, we generated a cell line by repeated in vitro antigenic
      stimulation of purified splenic CD4+ T lymphocytes from a chronically Trypanosoma
      cruzi-infected mouse. Cells from this line were confirmed to be CD4+ CD8- and
      proliferated upon stimulation with soluble heart antigens from different animal
      species, as well as with T. cruzi antigen, in the presence of syngeneic feeder
      cells. In vitro antigen stimulation of the cell line produced a Th1 cytokine
      profile, with high levels of IFNgamma and IL-2 and absence of IL-4, IL-5 and IL
      10. The cell line also terminated the beating of fetal heart clusters in vitro
      when cocultured with irradiated syngeneic normal spleen cells. In situ injection
      of the cell line into well established heart transplants also induced the
      cessation of heart beating. Finally, adoptive transfer of the cell line to heart
      immunized or T. cruzi-infected BALB/c nude mice caused intense heart
      inflammation.

PMID- 11240901
TI  - Immune responses to multiple antigen peptides containing T and B epitopes from
      Plasmodium falciparum circumsporozoite protein of Brazilian individuals naturally
      exposed to malaria.
AB  - We have evaluated the immune responses of individuals living in a malaria endemic
      area of Brazil to the (T1B)4, a multiple antigen peptide (MAP) from Plasmodium
      falciparum circumsporozoite (CS) protein and the related monoepitope MAPs, B4 and
      (T1)4, and the linear peptides, T1B and B. The highest antibody frequencies were
      against MAPs containing the B cell epitope sequence (T1B)4 (42.2%) and B4
      (28.8%), while the highest lymphoproliferative response frequencies were against
      the MAPs containing the T cell epitope sequence (T1)4 (47%) and (T1B)4 (36.4%).
      We analysed individual responses considering lymphoproliferative response to
      (T1)4 MAP and IgG antibody titre to (T1B)4 as patterns of ideal cellular and
      humoral responses, respectively. The frequency of responders, cellular and/or
      humoral was 66.6%, significantly higher than non responders (P = 0.003). We also
      determined the HLA class II haplotype of each individual but no association
      between these and immune response patterns to the MAPs was observed. The results
      showed that individuals primed against P. falciparum in their natural habitat,
      present a very diverse array of responses against the same peptide antigens,
      varying from no response in one-third of the individuals to cognate B and T cell
      responses. Our study underlines the importance of previous studies of vaccine
      candidates to guarantee that the immunization will be capable of reverting
      inefficient or absent responses to malaria epitopes.

PMID- 11240902
TI  - Oestrus ovis (Diptera: Oestridae): effects of larval excretory/secretory products
      on nitric oxide production by murine RAW 264.7 macrophages.
AB  - Larvae of Oestrus ovis (Insecta: Diptera: Oestridae) are common parasites of
      nasal and sinus cavities of sheep and goats. Previous studies revealed that crude
      extracts of larvae modify NO synthesis by ovine monocyte derived macrophages. The
      aim of this study was to investigate the larval excretory/secretory products
      effects on nitric oxide production by murine tumour macrophages RAW 264.7.
      Stimulation of RAW macrophages by excretory/secretory products of the three
      instars larvae (25 microg/ml) significantly increased nitrite concentrations in
      culture supernatants compared to negative and positive Escherichia coli
      lipopolysaccharide control. This effect was time and dose dependent. Nitrite
      production in culture supernatants was due to induction of isoform NOS-2 because
      both NG monomethyl L-arginine (100 microM) and dexamethasone (20 microM)
      inhibited, by 60 and 50%, respectively, nitrite accumulation in culture
      supernatants. First steps of purification, by ion exchange chromatography,
      indicated that one protein of 29 kDa was able to induce NO synthesis by
      macrophages. Further studies are needed for a better characterization of these
      molecule and to investigate their immunogenicity for a vaccine approach.

PMID- 11240903
TI  - A previous infection with Toxoplasma gondii does not protect against a challenge
      with Neospora caninum in pregnant sheep.
AB  - Sheep immunized with Toxoplasma gondii (Toxovax) prior to pregnancy were tested
      for their ability to withstand a challenge at 90 days gestation with 107 Neospora
      caninum (NC1) tachyzoites. The antibody responses in sheep following immunization
      with T. gondii were specific for T. gondii whereas peripheral blood mononuclear
      cells responded to both T. gondii and N. caninum antigen in vitro. This suggested
      that there was induction of crossreactive immune recognition in the sheep, at
      least at the cellular level. Following challenge of sheep at mid-gestation with
      N. caninum, no febrile responses were recorded in the group of sheep which had
      previously received Toxovax while significant febrile responses were recorded in
      the group of sheep which received N. caninum challenge alone. Antibody responses
      to N. caninum developed in all sheep following N. caninum challenge and antibody
      responses to T. gondii were boosted in the group of sheep which had previously
      been immunized with Toxovax. No antibodies to T. gondii were observed in the
      sheep which received the N. caninum challenge alone. Peripheral blood mononuclear
      cells from both groups of sheep responded to T. gondii and N. caninum antigen in
      vitro and interferon gamma was present in the cell-free supernatant from
      activated cells. However despite evidence of the induction of crossreactive
      immunity between T. gondii and N. caninum, this was not sufficient to prevent
      foetal death. The group of sheep which had received Toxovax prior to pregnancy
      and the group of sheep which only received the N. caninum challenge experienced
      100% foetal death compared with 0% in the unchallenged control group. Vaccination
      prior to pregnancy with Toxovax did protect against foetal death following oral
      challenge at 90 days with 2000 T. gondii oocysts which caused 100% foetal death
      in a control challenge group.

PMID- 11240904
TI  - Cutaneous interleukin-7 transgenic mice display a propitious environment to
      Schistosoma mansoni infection.
AB  - Interleukin (IL)-7 is produced early in Schistosoma mansoni-infected human and
      murine skin and was recently shown to favour parasite development. In the present
      work, we investigated the participation of keratinocyte-derived IL-7 in this
      process. Keratinocytes are the predominant cellular constituents of the epidermis
      and the first tissue encountered by the parasite when it infects the vertebrate
      host. We therefore infected IL-7 cutaneous transgenic mice and compared several
      parasitological and immunological parameters to those of infected littermate
      controls. In transgenic mice, an increased number of total adult worms was
      observed while egg number and female fecundity remained unchanged. Additionally,
      transgenic animals displayed a more intensive hepatic fibrosis. In parallel,
      infected IL-7 transgenic animals showed a dominant Th2-type humoral response
      towards egg antigens. The results presented here confirm and reinforce the key
      role play by IL-7 in S. mansoni-vertebrate host interplay, beginning with
      keratinocyte-derived IL-7.

PMID- 11240905
TI  - A calreticulin-like molecule from the human hookworm Necator americanus interacts
      with C1q and the cytoplasmic signalling domains of some integrins.
AB  - Calreticulin was recently identified as a hookworm (Necator americanus) allergen,
      implying secretion, and contact with cells of the immune system, or significant
      worm attrition in the tissues of the host. As human calreticulin has been shown
      to bind to and neutralize the haemolytic activity of the complement component
      C1q, and to be putatively involved in integrin-mediated intracellular signalling
      events in platelets, it was of interest to determine whether a calreticulin from
      a successful nematode parasite of humans, with known immune modulatory and
      antihaemostatic properties, exhibited a capacity to interfere with complement
      activation and to interact with integrin domains associated with cell signalling
      in platelets and other leucocytes. We can now report that recombinant
      calreticulin failed to demonstrate significant calcium binding capacity, which is
      a hallmark of calreticulins in general and may indicate inappropriate folding
      following expression in a prokaryote. Nevertheless, recombinant calreticulin
      retained sufficient molecular architecture to bind to, and inhibit the haemolytic
      capacity of, human C1q. Furthermore, recombinant calreticulin reacted in surface
      plasmon resonance analysis (SPR) with peptides corresponding to cytoplasmic
      signalling domains of the integrins alphaIIb and alpha5, in a calcium independent
      manner. SPR was also used to ratify the specificity of a polyclonal antibody to
      hookworm calreticulin, which was then used to assess the stage specificity of
      expression of the native molecule (in comparison with reverse transcriptase
      polymerase chain reaction), to indicate its apparent secretion, and to purify
      native calreticulin from worm extracts by affinity chromatography. This
      development will allow the functional tests described above to be repeated for
      native calreticulin, to ascertain its role in the host-parasite relationship.

PMID- 11240906
TI  - Vaccine efficacy of recombinant cathepsin D aspartic protease from Schistosoma
      japonicum.
AB  - Mice were vaccinated with recombinant Schistosoma japonicum cathepsin D aspartic
      protease, expressed in both insect cells and bacteria, in order to evaluate the
      vaccine efficacy of the schistosome protease. Mean total worm burdens were
      significantly reduced in vaccinated mice by 21-38%, and significant reductions in
      female worm burdens were also recorded (22-40%). Vaccination did not reduce
      fecundity; rather, we recorded increased egg output per female worm in vaccinated
      animals, suggesting a crowding effect. Vaccinated mice developed high levels of
      antibodies (predominantly IgG1, IgG2a and IgG2b isotypes), but there was no
      correlation between antibody levels and protective efficacy. Immune sera from
      vaccinated mice did not inhibit the in vitro degradation of human haemoglobin by
      the recombinant protease, and passive transfer of serum or antibodies from
      vaccinated animals, before and after parasite challenge, did not significantly
      reduce worm or egg burdens in recipient animals. These results suggest that
      antibodies may not play a key role in the protective effect elicited, and that
      protection may be due to a combination of humoral and cell-mediated responses

PMID- 11240907
TI  - Human Bancroftian filariasis: loss of patent microfilaraemia is not associated
      with production of antibodies to microfilarial sheath.
AB  - Antisheath antibodies have been incriminated in elimination of circulating
      microfilariae in human filariasis since a very significant inverse association
      has been consistently demonstrated between the two parameters. An attempt was
      made in the present study to seek empirical proof for the above proposal. Two
      cohorts of 43 and 73 microfilariae (mf) carriers were examined after 13 and 10
      years, respectively, for mf as well as antisheath antibodies. The first cohort
      was also examined for the presence of circulating filarial antigen (CFA). Of the
      43 mf carriers examined after 13 years, 62.8% were free of circulating mf
      although only 3.7% of them had demonstrable antisheath antibodies. Approximately
      93% of this cohort (with or without current microfilaraemia) tested positive for
      CFA after 13 years indicating continued presence of adult filarial worms in the
      host after loss of mf in circulation. When the second cohort of 73 mf carriers
      were examined after 10 years, 30 were found to be amicrofilaraemic and only 6.66%
      of them had demonstrable antisheath antibodies. We conclude that, in human
      Bancroftian filariasis, elimination of circulating microfilariae may not be
      mediated by antibodies to microfilarial sheath.

PMID- 11240909
TI  - Does the chloroplast small heat shock protein protect photosystem II during heat
      stress in vitro?
AB  - It has been suggested that the function of the chloroplast-localized small heat
      shock protein (sHsp) is to protect photosystem II (PSII) from heat inactivation.
      This paper reports that addition of purified sHsp protein to isolated thylakoid
      membranes gave no protection of PSII and questions that there is any direct
      effect of the sHsp on PSII. The opinion is forwarded that the primary role for
      the chloroplast-localized sHsp may not even be protection of PSII.

PMID- 11240908
TI  - Advances in the selection of transgenic plants using non-antibiotic marker genes.
AB  - Production of transgenic plants started more than a decade ago, but it is still a
      time-consuming operation. One of the critical points is the selection procedure
      used for the recovery of transgenic shoots after transformation. Moreover, as
      more transgenic traits are to be incorporated into crops that already have been
      transformed, it is clear that there is a need for new methods with higher
      efficiencies. In this article, recently developed selection systems are reviewed.
      They differ from conventional selection techniques as they are based on
      supplementing the transgenic cells with a metabolic advantage rather than killing
      the non-transgenic cells. In many cases, these new selection systems have been
      found to be superior to conventional methods.

PMID- 11240910
TI  - Purification of a novel lipoxygenase from eggplant (Solanum melongena) fruit
      chloroplasts.
AB  - A novel membrane lipoxygenase (LOX; EC 1.13.11.12) from eggplant (Solanum
      melongena L. cv. Belleza negra) fruit chloroplasts has been purified 20-fold to a
      specific activity of 207 enzymatic units per mg of protein with a yield of 72%.
      The purification was carried out by sonicating the chloroplastic membranes in the
      presence of Triton X-114 followed by phase partitioning and anion exchange
      chromatography. The purified membrane LOX preparation consisted of a single major
      band with an apparent molecular mass of 97 kDa after sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. The results obtained using intact
      chloroplasts indicate that the enzyme is not localized in the stroma. When the
      enzyme reacts with linoleic acid, it produces a single peak, which comigrates
      with standard 9-hydroperoxy-octadecadienoic acid. A physiological role for this
      chloroplastic LOX is proposed.

PMID- 11240911
TI  - Partial purification and characterization of pyruvate kinase from the plant
      fraction of soybean root nodules.
AB  - Pyruvate kinase (PK, EC 2.7.1.40) was partially purified from the plant cytosolic
      fraction of N2-fixing soybean (Glycine max [L.] Merr.) root nodules. The
      partially purified PK preparation was completely free of contamination by
      phosphoenolpyruvate carboxylase (PEPC, EC 4.1.1.31), the other major
      phosphoenolpyruvate (PEP)-utilizing enzyme in legume root nodules. Latency
      experiments with sonicated nodule extracts showed that Bradyrhizobium japonicum
      bacteroids do not express either PK or PEPC activity in symbiosis. In contrast,
      free-living B. japonicum bacteria expressed PK activity, but not PEPC activity.
      Antibodies specific for the cytosolic isoform of PK from castor bean endosperm
      cross-reacted with a 52-kDa polypeptide in the partially purified PK preparation.
      At the optimal assay pH (pH 8.0 for PEPC and pH 6.9 for PK) and in the absence of
      malate, PEPC activity in crude nodule extracts was 2.6 times the corresponding PK
      activity. This would tend to favour PEP metabolism by PEPC over PEP metabolism by
      PK. However, at pH 7.0 in the presence of 5 mM malate, PEPC activity was strongly
      inhibited, but PK activity was unaffected. Thus, we propose that PK and PEPC
      activity in legume root nodules may be coordinately regulated by fluctuations in
      malate concentration in the plant cytosolic fraction of the bacteroid-containing
      cells. Reduced uptake of malate by the bacteroids, as a result of reduced rates
      of N2 fixation, may favour PEP metabolism by PK over PEP metabolism by PEPC.

PMID- 11240912
TI  - Increased glutamine synthetase activity and changes in amino acid pools in leaves
      treated with 5-aminoimidazole-4-carboxiamide ribonucleoside (AICAR).
AB  - Feeding 5-aminoimidazole-4-carboxiamide ribonucleoside (AICAR) through the
      petiole of detached young barley leaves rapidly increased activities of NADH
      nitrate reductase (NR) and glutamine synthetase (GS) in leaf extracts and at
      least partly prevented the usual slow decrease of these enzyme activities during
      prolonged illumination. Further, AICAR caused drastic changes in amino acid
      levels: glutamine and serine levels were increased whereas glutamate and glycine
      were decreased, probably indicating a higher GS activity and more rapid
      conversion of glycine into serine. The latter may be responsible for the higher
      ammonium contents found in AICAR treated leaves. We tentatively suggest that GS
      (located in the chloroplast) and glycine decarboxylase (located in the
      mitochondria) are regulated in a manner similar to NR. This is discussed in the
      light of recent reports that 14-3-3 isoforms exist in chloroplasts and that GS
      binds to 14-3-3s in vitro.

PMID- 11240913
TI  - Differential response of antioxidant enzymes in leaves of necrotic wheat hybrids
      and their parents.
AB  - The leaves of necrotic hybrid of wheat (Triticum aestivum L.) exhibited high
      superoxide content associated with increased lipid peroxidation and membrane
      damage in earlier studies (Khanna-Chopra et al. 1998, Biochem Biophys Res Commun
      248: 712-715; Dalal and Khanna-Chopra 1999, Biochem Biophys Res Commun 262: 109
      112). In the present study, we investigated the activities of the antioxidant
      enzymes in the leaves of necrotic wheat hybrids, KalyansonaxC306 (KxC) and
      WL711xC306 (WLxC) and their parents at different developmental stages. The KxC
      hybrid exhibited more severe necrosis than WLxC. In KxC, superoxide dismutase
      (SOD) activity showed no increase over the parents, while WLxC showed an early
      increase, but it was possibly insufficient to scavenge increased superoxide.
      Activities of guaiacol peroxidase, ascorbate peroxidase and glutathione reductase
      were enhanced, while catalase exhibited a decrease in activity, with the
      appearance of visible necrosis in both the hybrids. The isozyme profile of the
      antioxidant enzymes was similar in the hybrids and their parents. One existing
      isoform of guaiacol peroxidase showed an early appearance in the hybrid and
      increased in intensity with the progression of necrosis. The results reveal a
      differential response of antioxidant enzymes in necrotic wheat hybrids as
      compared to their parents. The response differed in magnitude at developmental
      stages of the leaves, which might be related to the intensity of necrosis
      expressed by the hybrids.

PMID- 11240914
TI  - Elevated CO2 and ozone reduce nitrogen acquisition by Pinus halepensis from its
      mycorrhizal symbiont.
AB  - The effects of 700 umol mol-1 CO2 and 200 nmol mol-1 ozone on photosynthesis in
      Pinus halepensis seedlings and on N translocation from its mycorrhizal symbiont,
      Paxillus involutus, were studied under nutrient-poor conditions. After 79 days of
      exposure, ozone reduced and elevated CO2 increased net assimilation rate.
      However, the effect was dependent on daily accumulated exposure. No statistically
      significant differences in total plant mass accumulation were observed, although
      ozone-treated plants tended to be smaller. Changes in atmospheric gas
      concentrations induced changes in allocation of resources: under elevated ozone,
      shoots showed high priority over roots and had significantly elevated N
      concentrations. As a result of different shoot N concentration and net carbon
      assimilation rates, photosynthetic N use efficiency was significantly increased
      under elevated CO2 and decreased under ozone. The differences in photosynthesis
      were mirrored in the growth of the fungus in symbiosis with the pine seedlings.
      However, exposure to CO2 and ozone both reduced the symbiosis-mediated N uptake.
      The results suggest an increased carbon cost of symbiosis-mediated N uptake under
      elevated CO2, while under ozone, plant N acquisition is preferentially shifted
      towards increased root uptake.

PMID- 11240915
TI  - Response of antioxidative enzymes to plum pox virus in two apricot cultivars.
AB  - Recent evidence has indicated that activated oxygen species (AOS) may function as
      molecular signals in the induction of defence genes. In the present work, the
      response of antioxidative enzymes to the plum pox virus (PPV) was examined in two
      apricot (Prunus armeniaca L.) cultivars, which behaved differently against PPV
      infection. In the inoculated resistant cultivar (Goldrich), a decrease in
      catalase (CAT) as well as an increase in total superoxide dismutase (SOD) and
      dehydroascorbate reductase (DHAR) activities were observed. Ascorbate peroxidase
      (APX), glutathione reductase (GR) and monodehydroascorbate reductase (MDHAR) did
      not change significantly in relation to non-inoculated (control) plants. In the
      susceptible cultivar (Real Fino), inoculation with PPV brought about a decrease
      in CAT, SOD and GR, whereas a rise in APX, MDHAR and DHAR activities was found in
      comparison to non-inoculated (control) plants. Apricot leaves contain only CuZn
      SOD isozymes, which responded differently to PPV depending on the cultivar.
      Goldrich leaves contained 6 SODs and both SOD 1 and SOD 2 increased in the
      inoculated plants. In leaves from Real Fino, 5 SODs were detected and only SOD 5
      was increased in inoculated plants. The different behaviour of SODs (H2O2
      generating enzymes) and APX (an H2O2-remover enzyme) in both cultivars suggests
      an important role for H2O2 in the response to PPV of the resistant cultivar, in
      which no change in APX activity was observed. This result also points to further
      studies in order to determine if an alternative H2O2-scavenging mechanism takes
      place in the resistant apricot cultivar exposed to PPV. On the other hand, the
      ability of the inoculated resistant cultivar to induce SOD 1 and SOD 2 as well as
      the important increase of DHAR seems to suggest a relationship between these
      activities and resistance to PPV. This is the first report about the effect of
      PPV infection on the antioxidative enzymes of apricot plants. It opens the way
      for the further studies, which are necessary for a better understanding of the
      role of antioxidative processes in viral infection by PPV in apricot plants.

PMID- 11240916
TI  - Growth temperature can alter the temperature dependent stimulation of
      photosynthesis by elevated carbon dioxide in Albutilon theophrasti.
AB  - Stimulation of photosynthesis in response to elevated carbon dioxide
      concentration [CO2] in the short-term (min) should be highly temperature
      dependent at high photon flux. However, it is unclear if long-term (days, weeks)
      adaptation to a given growth temperature alters the temperature-dependent
      stimulation of photosynthesis to [CO2]. In velveltleaf (Albutilon theophrasti),
      the response of photosynthesis, determined as CO2 assimilation, was measured over
      a range of internal CO2 concentrations at 7 short-term measurement (12, 16, 20,
      24, 28, 32, 36 degrees C) temperatures for each of 4 long-term growth (16, 20, 28
      and 32 degrees C) temperatures. In vivo estimates of VCmax, the maximum RuBP
      saturated rate of carboxylation, and Jmax, the light-saturated rate of potential
      electron transport, were determined from gas exchange measurements for each
      temperature combination. Overall, previous exposure to a given growth temperature
      adjusted the optimal temperatures of Jmax and VCmax with subsequently greater
      enhancement of photosynthesis at elevated [CO2] (i.e., a greater enhancement of
      photosynthesis at elevated [CO2] was observed at low measurement temperatures for
      A. theophrasti grown at low growth temperatures compared with higher growth
      temperatures, and vice versa for plants grown and measured at high temperatures).
      Previous biochemical based models used to predict the interaction between rising
      [CO2] and temperature on photosynthesis have generally assumed no growth
      temperature effect on carboxylation kinetics or no limitation by Jmax. In the
      current study, these models over predicted the temperature dependence of the
      photosynthetic response to elevated [CO2] at temperatures above 24 degrees C. If
      these models are modified to include long-term adjustments of Jmax and VCmax to
      growth temperature, then greater agreement between observed and predicted values
      was obtained.

PMID- 11240917
TI  - Nitrate reduction in tendrils of semi-leafless pea.
AB  - The recessive gene af produces a modification of Pisum sativum L. leaf
      morphology, where leaflets are replaced by tendrils. Previous reports have
      suggested that tendrils may contribute to plant growth in a similar way to flat
      leaf structures, but these reports have been restricted to carbon metabolism. In
      this work, we investigate the nitrate reduction (nitrate reductase activity)
      capacity of tendrils of a semi-leafless variety, Solara, in relation to other
      leaf structures. Maximum nitrate reductase activity (EC 1.6.6.1), expressed on a
      protein basis, was significantly lower in tendrils compared to flat structures.
      However, the activation state of nitrate reductase was significantly higher in
      tendrils, reaching 70%, compared to flat leaf structures. According to these
      results, tendrils contributed up to 25% of the overall plant nitrate reduction in
      the semi-leafless variety. This figure was even higher when nitrate reduction was
      calculated from in vivo measurements. The results are discussed in relation to
      nitrate, magnesium, carbohydrates, amino acids and adenylate levels of tendrils.

PMID- 11240918
TI  - Characterization and expression of two members of the peach 1-aminocyclopropane-1
      carboxylate oxidase gene family.
AB  - The characterization and expression of PP-ACO1 and PP-ACO2, two members of the
      peach 1-aminocyclopropane-1-carboxylate (ACC) oxidase (ACO) gene family, are
      reported. PP-ACO1 is organized in 4 exons interrupted by 3 introns, whereas PP
      ACO2 has only 2 of the 3 introns present in PP-ACO1. Comparison of the deduced
      amino acid sequences of PP-ACO1 and PP-ACO2 reveals a 77.7% identity. PP-ACO1 and
      PP-ACO2 show highest degree of similarity with petunia (PH-ACO3; 84.1%) and apple
      (85.4%) ACO genes, respectively. PP-ACO1 is expressed in flowers, fruitlet
      abscission zones, mesocarp and in young fully expanded leaves. PP-ACO1 transcript
      accumulation strongly increases during fruitlet abscission, in ripe mesocarp and
      senescing leaves, and is enhanced by propylene. PP-ACO2 mRNA accumulation is
      detected in fruits only during early development and is unaffected by propylene
      treatment. Both ACO genes are expressed in epicotyl and roots of growing
      seedlings, although a stronger accumulation of PP-ACO2 mRNA is observed.

PMID- 11240919
TI  - Dark-inducible genes from Arabidopsis thaliana are associated with leaf
      senescence and repressed by sugars.
AB  - We have isolated 5 cDNA clones (din2, din6, din9, din10 and din11) corresponding
      to genes, the transcripts of which accumulated in leaves of Arabidopsis thaliana
      kept in the dark. These cDNA clones encode proteins similar to beta-glucosidase
      (EC 3.2.1.21, din2), asparagine synthetase (EC 6.3.5.4, din6), phosphomannose
      isomerase (EC 5.3.1.8, din9), seed imbibition protein (din10) and 2-oxoacid
      dependent dioxygenases (din11). Accumulation of the transcripts from din6 and
      din10 occurred within 3 h after plants were transferred to darkness. The
      transcripts from din2, din9 and din11 were only detected after 24 h of dark
      treatment. We also observed the accumulation of the din transcripts in senescing
      leaves. Application of a photosynthesis inhibitor, 3-(3,4-dichlorophenyl)-1-1
      dimethyl-urea, induced the expression of the din genes under illumination.
      Application of sucrose to detached leaves suppressed the accumulation of the din
      transcripts in the dark. These results indicate that expression of these genes
      partly depends on cellular sugar level. The sugar-modulated expression of the din
      genes suggests that dark-induced expression of these genes might be related to
      sugar starvation occurring in leaf cells in the dark, when the photosynthesis is
      hindered.

PMID- 11240920
TI  - Identification and characterization of soluble and insoluble myrosinase
      isoenzymes in different organs of Sinapis alba.
AB  - Extraction of Sinapis alba seeds under native conditions solubilized 3 myrosinase
      isoforms, pool I, II and III, which could be separated by ion exchange
      chromatography. Sequencing of numerous peptides of the I and III isoforms showed
      that they belonged to the Myrosinase A (MA) family of myrosinases and that they
      were encoded by different genes. Western blot analysis of S. alba seed proteins,
      extracted with a sodium dodecyl sulphate-containing buffer, using an anti
      myrosinase monoclonal antibody, showed the presence of two additional myrosinase
      isoforms with approximate molecular sizes of 62 and 59 kDa. These myrosinases,
      which only could be solubilized from seeds by inclusion of denaturing agents in
      the extraction buffer, were by sequence analysis identified as MB myrosinases.
      These isoenzymes or very similar forms were also present in seedling cotyledons.
      However, from this tissue, they could be extracted with non-denaturing buffers.
      In addition, cotyledons contained a 65-kDa MB myrosinase not found in seeds. In
      contrast, seedling cotyledons contained only minute amounts of pool I and no pool
      III MA myrosinases, emphasizing the tissue-specific expression of the
      corresponding gene families. Sequence analysis of myrosinase cDNAs generated cDNA
      by reversed transcription-polymerase chain reaction using degenerate primers with
      mRNA isolated from seeds, cotyledons and leaves confirmed the result that the MA
      isoforms were expressed only in seed tissue, while MB myrosinases were found in
      all tissues investigated. Furthermore, seed and leaf contained unique MB
      myrosinase transcripts, suggesting organ-specific expression of individual MB
      genes.

PMID- 11240921
TI  - DNA fragmentation in cereal roots indicative of programmed root cortical cell
      death.
AB  - In cereals, a progressively increasing root cortical cell death (RCD) occurs from
      the root tip and upwards when measured with vital staining methods. In this
      study, nuclear DNA fragmentation was studied in seminal root segments of wheat
      and barley in order to investigate if the cell death resembled apoptosis. The
      fraction of cells with TUNEL-positive nuclei increased gradually with increasing
      root age in both the cortex and the stele. Southern analysis showed a typical
      ladder pattern, indicating nucleosomal fragmentation already in 2-day-old root
      segments, and this became more pronounced in older root segments. DNA
      fragmentation appeared to be more extensive in wheat than in barley roots. These
      results confirm earlier studies, where RCD has been found to be earlier initiated
      and to proceed at a faster rate in wheat. The characteristic DNA fragmentation
      found in the roots indicates programmed cell death with mechanistic similarities
      to apoptosis. Ultrastructural examination of nuclei in cortex cells with
      transmission electron microscopy revealed an increased chromatin condensation in
      older roots, particularly in wheat. In addition, we found nucleosomal DNA ladders
      in young leaf tissue from wheat but not from barley.

PMID- 11240922
TI  - Response to auxin changes during maturation-related loss of adventitious rooting
      competence in loblolly pine (Pinus taeda) stem cuttings.
AB  - Hypocotyl cuttings (from 20- and 50-day-old Pinus taeda L. seedlings) rooted
      readily within 30 days in response to exogenous auxin, while epicotyl cuttings
      (from 50-day-old seedlings) rarely formed roots within 60 days. Responses to
      auxin during adventitious rooting included the induction of cell reorganization
      and cell division, followed by the organization of the root meristem. Explants
      from the bases of both epicotyl and hypocotyl cuttings readily formed callus
      tissue in response to a variety of auxins, but did not organize root meristems.
      Auxin-induced cell division was observed in the cambial region within 4 days, and
      later spread to the outer cortex at the same rate in both tissues. Cells at
      locations that would normally form roots in foliated hypocotyl cuttings did not
      produce callus any differently than those in other parts of the cortex.
      Therefore, auxin-induced root meristem organization appeared to occur
      independently of auxin-induced cell reorganization/division. The observation that
      N-(1-naphthyl)phthalamic acid (NPA) promoted cellular reorganization and callus
      formation but delayed rooting implies the existence of an auxin signal
      transduction pathway that is specific to root meristem organization. Attempts to
      induce root formation in callus or explants without foliage were unsuccessful.
      Both the cotyledon and epicotyl foliage provided a light-dependent product other
      than auxin that promoted root meristem formation in hypocotyl cuttings.

PMID- 11240923
TI  - The role of sucrose during maturation of black spruce (Picea mariana) and white
      spruce (Picea glauca) somatic embryos.
AB  - The present study was conducted to understand the role of sucrose in the medium
      on the maturation of black spruce and white spruce somatic embryos. A maturation
      medium containing 6% sucrose, which hydrolyzed into glucose and fructose, gave
      significantly more embryos than a medium containing 3.16% of each glucose and
      fructose. Preventing the complete sucrose hydrolysis by a daily transfer of the
      tissues onto fresh medium significantly decreased the yield of somatic embryos
      compared to when sucrose was allowed to complete its hydrolysis. This reduction
      was not due to the manipulation of the tissues during the transfer, since a daily
      in situ transfer did not affect embryo production. To verify if the better embryo
      production observed on a medium containing 6% sucrose was due to the increasing
      osmotic pressure of the medium, this increasing osmotic pressure was simulated
      with a sequence of media containing different concentrations of glucose and
      fructose. Unexpectedly and for both species, this simulation did not improve
      somatic embryo production, which stayed similar to the one obtained on constant
      osmotic pressure. To understand these results, embryos produced on the different
      treatments were analyzed in terms of sucrose, glucose, fructose and starch levels
      and protein contents. The embryo carbohydrate content was independent from the
      carbohydrate used in the maturation medium. However, embryos matured on 6%
      sucrose allowed to hydrolyze during the maturation period contained significantly
      more soluble and insoluble proteins than embryos matured on any other treatment.
      Furthermore, embryos with a higher protein content also exhibited a higher
      epicotyl appearance frequency. The role of sucrose as a regulatory factor during
      the maturation of spruce somatic embryos is discussed.

PMID- 11240924
TI  - Endogenous hormone levels in explants and in embryogenic and non-embryogenic
      cultures of carrot.
AB  - Carrot (Daucus carota L. F1 hybrid Starca) excised hypocotyls were cultured on
      Murashige and Skoog medium with and without 2,4-dichlorophenoxy acetic acid (2,4
      D) to determine the effect of this plant growth regulator on their further
      development and their endogenous hormone levels. Culture in the absence of 2,4-D
      stimulated root development at one end of the hypocotyl segments and increased
      the endogenous levels of free indole-3-acetic acid (IAA), zeatin/zeatin riboside
      and N6(Delta2-isopentenyl) adenine/N6(Delta2-isopentenyl) adenosine, as
      determined by radio-immunoassay. On the other hand, the presence of 2,4-D in the
      culture medium promoted callus induction and proliferation, together with
      abscisic acid (ABA) accumulation, in the hypocotyl segments during the first
      weeks of culture. When the callus segments generated in the hypocotyl sections
      cultured in the presence of 2,4-D were cultivated further, the development of two
      callus types was observed, one composed of preglobular and globular embryos and
      the other translucent, watery and lacking any sign of organisation. The embryos
      of the first type germinated when callus segments were transferred to
      regeneration conditions, while no change was observed when the second type was
      induced to regenerate. Higher levels of free IAA and ABA were obtained in the
      embryogenic calli when compared to the non-embryogenic, while no differences were
      observed among callus types in the other hormones evaluated. The possible role of
      the different plant hormones during induction of somatic embryogenesis is
      discussed.

PMID- 11240925
TI  - Bimodal patterns of floral gene expression over the two seasons that kiwifruit
      flowers develop.
AB  - Polymerase chain reaction fragments with homology to the Arabidopsis floral
      meristem identity genes LEAFY and APETALA1 have been isolated from kiwifruit
      (Actinidia deliciosa [A. Chev.] C. F. Liang and A. R. Ferguson) and have been
      named ALF and AAP1, respectively. Northern hybridisation analyses have shown that
      ALF and AAP1 have bimodal patterns of annual expression in developing first-order
      axillary buds and their subsequent shoots. This pattern of expression is
      consistent with the 2-year cycle of axillary bud, flower and fruit development
      observed in kiwifruit. The first period of expression was early in first-order
      bud development (late spring of the first growing season), when second-order
      meristems are initiated, and the second, approximately 10 months later, when
      those meristems differentiate flowers (late spring of the second growing season).
      In situ hybridisation analyses on axillary buds collected during late spring of
      the first growing season have shown ALF expression throughout the developing
      first-order buds and AAP1 expression was localised in developing second-order
      axillary meristems. During the spring of the second growing season, transcript
      accumulation for both ALF and AAP1 is localised in differentiating flowers. Our
      results show that important developmental events are occurring very early in
      kiwifruit first-order axillary bud development (spring of the first growing
      season) and it is likely that this includes floral commitment (evocation).

PMID- 11240926
TI  - Effects of light quality on somatic embryogenesis in Araujia sericifera.
AB  - The effects of photoperiod, light quality and end-of-day (EOD) phytochrome
      photoconversion on somatic embryogenesis (SE) of Araujia sericifera petals have
      been studied. Petals from immature flowers were cultured under 8- and 16-h
      photoperiods using Gro-lux fluorescent lamps. The photon fluence rate was 90-100
      umol m-2 s-1 and the red (R):far-red (FR) ratio was 98. R, FR, R followed by FR
      (R-FR) and FR followed by R (FR-R) light treatments were applied for 3 weeks at
      the end of the photoperiods. In a set of experiments, DL-alpha
      difluoromethylarginine (DFMA) or methylglyoxal bis(guanylhydrazone) (MGBG), both
      inhibitors of polyamine biosynthesis, were added to the culture medium in order
      to study the involvement of polyamine metabolism. The level of SE was the same in
      long (LD) and short (SD) days. Thus, the light effect was accomplished after 8 h.
      All EOD treatments that decreased the Pfr level inhibited SE when applied after
      SD, but not after LD. The FR-R treatment after LD caused an additional
      stimulatory effect on SE, even in the presence of polyamine inhibitors. DFMA
      inhibited SE in both SD and LD, but MGBG did not modify SE in either SD or LD.
      The R, FR and R-FR treatments did not alter the level of SE when applied after LD
      in the presence of DFMA or MGBG. However, these treatments decreased SE after SD
      when the medium contained polyamine inhibitors. Our results suggest that Gro-lux
      lamps, which produce an extremely high R:FR ratio, promote SE in A. sericifera
      and a timing response to phytochrome photoconversion during photoperiodic
      induction. Thus, our data corroborate the involvement of phytochromes and
      polyamines in SE in A. sericifera, which responded as a light-dominant long-day
      plant.

PMID- 11240927
TI  - Relative control potential of abscisic acid, carbon dioxide and light in
      responses of Phaseolus vulgaris stomata.
AB  - We outline a theoretical framework for comparing the relative effectiveness of
      hormonal and other factors in the control of physiological responses. This
      involves determining a 'baseline' set of conditions, then adjusting each factor
      in turn with the others held constant. The initial rate of response to each
      change in condition is estimated and compared among factors to arrive at a
      quantitative indication of control potential under the specified baseline
      conditions - the control coefficient. The suitability of the stomatal response as
      a model system for such studies is discussed. A portable infra-red gas analyser
      was used to investigate the control potential of abscisic acid (ABA), CO2 and
      light - measured as photosynthetic photon flux density (PPFD) - over responses of
      Phaseolus vulgaris L. stomata at baseline conditions appropriate to an unstressed
      plant under moderate light conditions. The ranking of control coefficients
      observed under these conditions was light>CO2>ABA. The control coefficients of
      CO2 and ABA were 0.28 and 0.11 times that of light, respectively. These results
      are discussed in relation to the sensitivity of the plant material and the
      experimental conditions. Implications for a hormonal role for ABA in the control
      of stomatal movements are considered. We conclude that this method can provide
      valuable information concerning the relative control potential of hormonal and
      other influences in the context of differences in baseline conditions and in
      relation to changes in sensitivity of plant material.

PMID- 11240928
TI  - Further comments on surgery or not for fully accommodative esotropia.

PMID- 11240929
TI  - Adult strabismus: goals of realignment surgery.

PMID- 11240930
TI  - There's no longer any need for randomized control groups; it's time to regularly
      offer atropine and bifocals for school myopia; comments on evidence-based
      medicine.

PMID- 11240931
TI  - Surgery for Duane's Retraction Syndrome and superior oblique palsy, vergence
      adaptation in kids, depth perception in eye surgery; new surgery: IO-ANT?

PMID- 11240933
TI  - Outcome of inferior oblique recession with or without vertical rectus recession
      for unilateral superior oblique paresis.
AB  - PURPOSE: To determine the effectiveness of a standard fixed 10 mm inferior
      oblique (IO) recession with or without vertical rectus recession in visually
      mature patients with unilateral superior oblique paresis (SOP) and mild to
      moderate IO overaction. METHODS: The records of 24 patients over 12 years of age
      who had 10 mm IO recession for SOP, for IO overaction of +1 to +3 (out of maximum
      +4), with 6+ months of followup were reviewed. Criteria required for a
      "successful" outcome included: 1. hyperdeviation of 5delta or less in primary
      position; 2. elimination of any compensatory abnormal head posture; and 3.
      elimination of diplopia in the central 30 degrees of the binocular visual field.
      RESULTS: In 16 cases of IO recession alone, 88% were "successful" and in 8 cases
      who had in addition either contralateral inferior rectus recession or ipsilateral
      superior rectus recession, 75% were "successful". IO 10 mm recession alone led to
      an average reduction of 9.1 PD of hypertropia in primary position. CONCLUSION: A
      standard ungraded 10 mm recession of the IO alone or in combination with vertical
      rectus muscle recession is an effective weakening procedure with a high success
      rate for patients with unilateral SOP with mild to moderate IO overaction. In
      occasional cases of undercorrection, a subsequent IO myectomy is very feasible
      and effective.

PMID- 11240932
TI  - Outcome of surgery in 124 cases of Duane's Retraction Syndrome (DRS) treated by
      intraoperatively graduated recession of the medial rectus for esotropic DRS, and
      of the lateral rectus for exotropic DRS.
AB  - PURPOSE: To determine the outcome and effectiveness of simple horizontal muscle
      recession surgery in Duane's Retraction Syndrome (DRS). CASES & METHODS: A total
      of 194 cases of DRS were operated on by us during the past 25 years. Surgery was
      aimed at improving the binocular alignment and eye position at the primary
      position as well as any abnormal head posture. Sufficient data were available in
      124 cases. Recession of the medial rectus muscle was performed on 76 cases with
      esotropia and of the lateral rectus on 48 cases with exotropia. Recession dosage
      was determined during surgery based on three factors: size of the preoperative
      strabismus in primary position; forced ductions/resistance to traction, and the
      appearance of the rectus muscle at surgery. RESULTS: Both the primary eye
      position and the abnormal head posture were satisfactorily improved in 119 cases
      (89%) after surgery with a result rated "excellent" or "good" by a residual
      deviation of 7 degrees or less and a definitely improved abnormal head posture,
      for all types of DRS deviations. CONCLUSION: Recession of the appropriate
      horizontal rectus muscle is a safe and effective primary procedure for both the
      primary deviation and abnormal head posture in all types of DRS.

PMID- 11240934
TI  - Vergence adaptation in children and its clinical significance.
AB  - BACKGROUND AND PURPOSE: Vergence adaptation has not been well investigated in
      children even though it may contribute to binocular dysfunction and near work
      induced asthenopia. METHODS: We compared vergence adaptation in 18 children and
      18 young adult subjects by assessing tonic vergence (TV) before and immediately
      after a period of sustained near fixation, by measuring heterophoria with a
      synoptophore through 0.5 mm binocular pinholes. Adaptation was induced by a
      reading task at 15 cm for a continuous 5 minute period. RESULTS: Mean pre-task TV
      values of 0.70 MA (Meter Angles) and 0.20 MA were observed for the children and
      young adults, respectively (p = 0.08). The initial mean vergence adaptation for
      children and adults was +0.45 MA and +0.11 MA, respectively (p = 0.001).
      CONCLUSION: The greater vergence adaptation observed in children may impact upon
      the clinical assessment of their binocular vision, especially heterophoria
      measurement which may require longer periods of dissociation than previously
      recommended, and might also ultimately be partly responsible for the predominant
      development of esodeviations during childhood

PMID- 11240935
TI  - A case of persistent overcorrection after surgery for a superior oblique palsy.

PMID- 11240936
TI  - Anterior and nasal transposition of the inferior oblique muscle: a preliminary
      case report on a new procedure.
AB  - PURPOSE: To describe this new extraocular muscle surgery. METHOD: Case Report of
      a child in need of treatment of a weak superior oblique muscle which, at surgery,
      was in fact found to be absent. After a prior only partially successful recession
      of the antagonist inferior oblique (IO), the IO muscle was detached and
      transposed to a new insertion in the inferior nasal quadrant converting the
      muscle, as a result of its functional origin being the neurovascular bundle
      ["Ligament of Stager"-ed], from an extorter and elevator of the globe to an
      intorter and depressor. RESULT: Satisfactory binocular alignment was achieved.
      CONCLUSION: This new surgical procedure provides significant advantages, and
      should be added to our surgical armamentarium.

PMID- 11240937
TI  - Stereoacuity and depth perception decrease with increased instrument
      magnification: comparing a non-magnified system with lens loupes and a surgical
      microscope.
AB  - PURPOSE: To evaluate the effect of instrument magnification used in eye surgery
      on stereoacuity and depth perception. METHODS: Twenty-one subjects (10 clinical
      ophthalmologists familiar with loupes and operating microscopes and 11 non
      ophthalmologists) with normal near vision and stereoacuity were tested with the
      Randot Stereotest viewed unmagnified, with a 4x loupes (450 mm focal length), and
      with a 16x operating microscope. RESULTS: Total scores: 8 errors in 210 test
      steps with the unmagnified observations, 25/210 with loupes, and 30/210 with the
      microscope. The statistical differences in these scores were "statistically
      highly significant" for all three tests (p = 0.002); and "significant" for the
      unmagnified versus loupe (p = 0.007) and unmagnified versus microscope (p =
      0.002). Test viewing through the microscope, the greatest errors occurred (total
      errors = 1840 seconds of arc), less with the loupes (total 1150") and least
      without magnification (total 220"). Errors and scores for 10 experienced
      ophthalmologists were no different (p > or = 0.55, p = 1.00) from the 11 non
      ophthalmologist subjects. CONCLUSIONS: Stereoacuity and depth perception decrease
      when viewing a test target with loupes or with a microscope, with the effect
      worsening as magnification increases. Familiarity with the magnifying equipment
      did not improve stereoacuity.

PMID- 11240940
TI  - Cockroach allergens and asthma.
AB  - Asthma and allergy are the most common diseases associated with cockroach
      infestation of houses in the United States and other parts of the world.
      Sensitization and exposure to cockroach allergens is associated with increased
      asthma morbidity in the United States, especially among lower socioeconomic
      groups, including African American and Hispanic populations. Exposure to
      cockroach allergens in the first 3 months of life has been associated with
      repeated wheezing and asthma. The principal domestic cockroach species are
      Blattella germanica and Periplaneta americana. Both species produce several
      potent allergens, including Bla g 2 (inactive aspartic proteinase), Bla g 4
      (calycin), Bla g 5 (glutathione-S-transferase), the group 1 cross-reactive
      allergens Bla g 1 and Per a 1, and tropomyosin. Structural homology between
      tropomyosins from cockroaches, mites, and shrimp may explain clinical cases of
      the oral allergy syndrome. The 3-dimensional structures of several cockroach
      allergens are known, and biologically active recombinant allergens have been
      produced in high-level expression vectors. The use of recombinant cockroach
      allergens should allow mechanisms of cockroach-induced asthma to be investigated
      and may lead to the development of new approaches to asthma treatment.
      Environmental allergen measurements of Bla g 1 and Bla g 2 have allowed exposure
      levels that cause allergic sensitization to be established. Abatement studies
      have shown that a sustained decrease in cockroach allergen levels is difficult
      but can be accomplished by professional application of insecticides, together
      with rigorous household cleaning. Cockroach asthma is an important public health
      problem that affects patients who are the least likely to be compliant with
      treatment with asthma medications or environmental control. Patient education,
      improvements in the housing stock, and improvements in environmental and
      immunologic treatment strategies are likely to be the most successful approaches
      to reduce the prevalence of cockroach-induced asthma.

PMID- 11240941
TI  - IgE regulation and roles in asthma pathogenesis.
AB  - Asthma and the predisposition to produce IgE are inherited as linked traits in
      families. In patients IgE levels correlate with asthma severity and bronchial
      hyperresponsiveness. The concept that IgE plays a critical role in asthma
      pathogenesis has driven the development of IgE blockers, which are currently
      being introduced into clinical use. This review focuses on the mechanisms whereby
      IgE participates both in immediate hypersensitivity responses in the airways and
      in the induction of chronic allergic bronchial inflammation. The molecular
      genetic events that give rise to IgE production by B cells and the cellular and
      cytokine factors that support IgE production in the bronchial mucosal
      microenvironment are discussed. It is clear that much remains to be learned
      regarding the roles of IgE in asthma and the genetic and environmental influences
      that lead to its production. Over the next few years, the emerging experience
      with anti-IgE in patients will provide a more complete understanding of the
      mechanisms whereby IgE contributes to disease, as well as the therapeutic
      potential of its inhibition.

PMID- 11240942
TI  - Sublingual immunotherapy.
AB  - Recent claims have been made that sublingual immunotherapy (SLIT) may be a viable
      alternative to injection immunotherapy (SIT). Animal studies show that when
      allergens are administered topically, they are handled differently, and IgE
      responses can be reduced. Most published studies of human SLIT have been small
      but show fairly consistent benefits on symptom scores, with few systemic side
      effects. Objective measures of allergen reactivity usually do not change.
      Relatively few subjects have been treated in SLIT trials compared with the
      numbers that would be required to validate new drug therapies. On the plus side,
      SLIT appears to work in adults and in children; it offers some logistic
      advantages and seems to be safe. Giving allergen by mouth rather than by
      injection should decrease the costs of immunotherapy, but the cumulative dose of
      allergen used in SLIT has been between 20 to 375 times the dose given in
      conventional SIT. Further cost-benefit analysis is needed. On the other hand,
      standard SIT is effective and is supported by better clinical and experimental
      evidence. The balance sheet for SLIT is improving, but on the current evidence,
      SLIT requires further evaluation before it could be recommended for use in
      routine clinical practice.

PMID- 11240943
TI  - Tacrolimus: a new topical immunomodulatory therapy for atopic dermatitis.

PMID- 11240944
TI  - Persistent airflow limitation in adult-onset nonatopic asthma is associated with
      serologic evidence of Chlamydia pneumoniae infection.
AB  - BACKGROUND: Persistent airflow limitation may develop in patients with asthma,
      particularly in adults with nonatopic (intrinsic) disease. Although the
      underlying mechanisms are still unknown, respiratory infections might be
      involved. OBJECTIVE: We investigated the annual loss of lung function in relation
      to seropositivity to Chlamydia pneumoniae in different subgroups of patients with
      severe asthma according to age at onset of asthma and atopic status. METHODS: One
      hundred one nonsmoking outpatients with a pulmonologist's diagnosis of severe
      asthma (32 men and 69 women; mean age, 46.0 years; range, 18-75 years) were
      included in a cross-sectional study. C pneumoniae-specific serum IgG and IgA were
      measured by means of ELISA. The estimated decline in lung function was calculated
      from the relationship between postbronchodilator FEV(1)/vital capacity (percent
      predicted) and the duration of asthma and expressed as the slope of the
      regression line. RESULTS: Patients with adult-onset nonatopic asthma and positive
      IgG antibodies to C pneumoniae had a significantly steeper slope of the
      regression line compared with the other subgroups of asthmatic patients (P
      =.001), being indicative of a 4-fold greater estimated decline in
      postbronchodilator FEV(1)/vital capacity (2.3% vs 0.5% predicted per year of
      asthma duration). CONCLUSION: These results suggest that C pneumoniae infection
      might promote the development of persistent airflow limitation in patients with
      nonatopic adult-onset asthma. It remains to be established whether viable
      pathogens that are accessible for therapeutic intervention are still present in
      the lower airways.

PMID- 11240945
TI  - Systematic review: Exposure to pets and risk of asthma and asthma-like symptoms.
AB  - BACKGROUND: Studies of exposure to pets and risk of asthma have yielded
      conflicting results. OBJECTIVES: We performed a systematic review to synthesize
      the evidence of the effect of exposure to pets in the home on the risk of asthma
      and asthma-related symptoms. We also assessed differences between the studies as
      sources of heterogeneity of the results. METHODS: We conducted a MEDLINE search
      (until the end of 1999) using the following boolean search command: (asthma[all]
      OR wheez*[all]) AND (domestic animal*[all] OR pets[all]). The outcome was limited
      to either diagnosis of asthma or the symptom of wheezing. The exposure of
      interest was domestic animals in the home. Appropriate temporal relationship was
      defined as present in studies with either pet keeping within the first 2 years of
      life, in the past, or exposure to pets preceding the outcome. RESULTS: Thirty-two
      of the 217 retrieved articles fulfilled the eligibility criteria. Inappropriate
      time sequence of the exposure and outcome information was an important source of
      heterogeneity and an indication of potential selection bias. Therefore we
      analyzed studies focusing on early exposure or ensuring appropriate temporal
      sequence. The pooled risk estimates for both asthma (fixed-effects odds ratio,
      1.11; 95% CI, 0.98-1.25; heterogeneity, P =.04; random-effects odds ratio, 1.09;
      95% CI, 0.89-1.34) and wheezing (fixed-effects odds ratio, 1.19; 95% CI, 1.05
      1.35; heterogeneity, P =.03; random-effects odds ratio, 1.17; 95% CI, 0.95-1.44)
      indicated a small effect, which was limited to studies with a median study
      population age of over 6 years (fixed-effects odds ratio, 1.19; 95% CI, 1.02
      1.40; heterogeneity, P =.04; random-effects odds ratio, 1.15; 95% CI, 0.86-1.56;
      fixed-effects odds ratio, 1.29; 95% CI, 1.12-1.48; heterogeneity, P =.31). In
      younger children the harmful effect disappeared for wheezing (odds ratio, 0.80;
      95% CI, 0.59-1.08; P =.38). CONCLUSION: Exposure to pets appears to increase the
      risk of asthma and wheezing in older children. The observed lower risk among
      exposed than among unexposed young children is consistent with a protective
      effect in this age group but could also be explained by selection bias.

PMID- 11240946
TI  - Low-dose fluticasone propionate compared with montelukast for first-line
      treatment of persistent asthma: a randomized clinical trial.
AB  - BACKGROUND: Both inhaled corticosteroids and leukotriene modifiers are used in
      the maintenance treatment of persistent asthma. OBJECTIVE: The goal was to
      compare the efficacy and safety of low-dose fluticasone propionate (FP) and
      montelukast as first-line maintenance therapy in symptomatic patients by using
      short-acting beta2-agonists alone to treat persistent asthma. METHODS: In this
      multicenter, randomized, double-blind, double-dummy, parallel-group study, 533
      patients (>15 years old) with persistent asthma who remained symptomatic while
      taking short-acting beta2-agonists alone were treated with FP (88 microg [2 puffs
      of 44 microg] twice daily) or montelukast (10 mg once daily) for 24 weeks.
      RESULTS: Compared with treatment with montelukast, treatment with FP resulted in
      significantly greater improvements at endpoint in morning predose FEV(1) (22.9%
      vs 14.5%, P <.001), forced midexpiratory flow (0.66 vs 0.41 L/sec, P <.001),
      forced vital capacity (0.42 vs 0.29 L, P =.002), morning peak expiratory flow
      (PEF) (68.5 vs 34.1 L/min, P <.001), and evening PEF (53.9 vs 28.7 L/min, P
      <.001). Similar improvements in PEF were observed in patients with milder asthma
      (>70%-80% predicted FEV(1)). At endpoint, FP was more effective than montelukast
      at decreasing rescue albuterol use (3.1 puffs/day vs 2.3 puffs/day, P <.001),
      asthma symptom scores (-0.85 [48.6% decrease] vs -0.60 [30.5%], P <.001), and
      nighttime awakenings due to asthma (-0.64 awakenings/night [62% decrease] vs 
      0.48 awakenings/night [47.5%], P =.023), and FP increased the percentage of
      symptom-free days (32.0% vs 18.4% of days, P <.001) compared with montelukast.
      The adverse event and asthma exacerbation profiles for FP and montelukast were
      similar. CONCLUSIONS: Low-dose FP is more effective than montelukast as first
      line maintenance therapy for patients with persistent asthma who are undertreated
      and remain symptomatic while taking short-acting beta2-agonists alone.

PMID- 11240947
TI  - Nasal allergen provocation induces adhesion molecule expression and tissue
      eosinophilia in upper and lower airways.
AB  - BACKGROUND: Allergic rhinitis (AR) and asthma are characterized by means of a
      similar inflammatory process in which eosinophils are important effector cells.
      The migration of eosinophils from the blood into the tissues is dependent on
      adhesion molecules. OBJECTIVE: To analyze the aspects of nasobronchial cross
      talk, we studied the expression of adhesion molecules in nasal and bronchial
      mucosa after nasal allergen provocation (NP). METHODS: Nine nonasthmatic subjects
      with seasonal AR and 9 healthy control subjects underwent NP out of season.
      Bronchial and nasal biopsy specimens were taken before (T(0)) and 24 hours after
      NP (T(24)). Mucosal sections were analyzed for the presence of eosinophils, IL-5,
      eotaxin, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion
      molecule 1 (VCAM-1), E-selectin, and human endothelium (CD31). RESULTS: At T(24),
      an influx of eosinophils was detected in nasal epithelium (P =.01) and lamina
      propria (P <.01), as well as in bronchial epithelium (P =.05) and lamina propria
      (P <.05), of the patients with AR. At T(24), increased expression of ICAM-1, as
      well as increased percentages of ICAM-1+, VCAM-1+, and E-selectin+ vessels, were
      seen in nasal and bronchial tissue of patients with AR. The number of mucosal
      eosinophils correlated with the local expression of ICAM-1, E-selectin, and VCAM
      1 in patients with AR. CONCLUSION: This study shows that NP in patients with AR
      results in generalized airway inflammation through upregulation of adhesion
      molecules.

PMID- 11240948
TI  - IL-16 inhibits IL-5 production by antigen-stimulated T cells in atopic subjects.
AB  - BACKGROUND: We have previously shown increased expression of the CD4+ cell
      chemoattractant IL-16 at sites of airway allergic inflammation. Little is known
      about the significance of IL-16 in allergic inflammation and its role in allergen
      driven T-cell cytokine responses. Because IL-16 interacts specifically with CD4+
      T cells, we hypothesized that IL-16 released at sites of inflammation may
      modulate the pattern of cytokines produced by CD4+ T cells. OBJECTIVE: We
      investigated the effects of exogenous rhIL-16 on cytokine production of PBMCs
      from atopic and nonatopic subjects in response to antigen and PHA. METHODS:
      Primary cultures of freshly isolated PBMCs from ragweed-sensitive atopic subjects
      and nonatopic subjects were stimulated with ragweed or PHA in the presence or
      absence of rhIL-16. Supernatant levels of IL-4, IL-5, and IFN-gamma were
      determined by means of ELISA at different time points between 2 and 6 days.
      Effects of IL-16 on antigen-induced cellular proliferative responses were
      determined. RESULTS: No IL-4 protein was detected after antigen stimulation of
      PBMCs from atopic subjects, whereas significant levels of IL-5 were measured on
      day 6 (median, 534.9 pg/mL). IL-5 secretion was abolished in PBMC cultures
      depleted of CD4+ cells. The addition of rhIL-16 in antigen-stimulated PBMC
      cultures significantly reduced the amount of IL-5 released (median, 99.8 pg/mL; P
      <.001). Detectable levels of IFN-gamma (median, 53.3 pg/mL) were identified after
      antigen stimulation. The addition of rhIL-16 in antigen-stimulated PBMC cultures
      significantly increased IFN-gamma levels (median, 255.6 pg/mL; P <.05). Effects
      of rhIL-16 appear to be specific for antigen-stimulated PBMCs in atopic subjects
      because rhIL-16 did not alter IL-5 or IFN-gamma production in response to PHA nor
      did rhIL-16 alter cytokine production in nonatopic normal subjects. CONCLUSION:
      These studies suggest that IL-16 can play a role in regulating the production of
      cytokines seen in allergic states in response to antigen.

PMID- 11240949
TI  - Counterbalancing of TH2-driven allergic airway inflammation by IL-12 does not
      require IL-10.
AB  - BACKGROUND: Asthma is characterized by allergen-induced airway inflammation
      orchestrated by TH2 cells. The TH1-promoting cytokine IL-12 is capable of
      inhibiting the TH2-driven allergen-induced airway changes in mice and is
      therefore regarded as an interesting strategy for treating asthma. OBJECTIVE: The
      antiallergic effects of IL-12 are only partially dependent of IFN-gamma. Because
      IL-12 is a potent inducer of the anti-inflammatory cytokine IL-10, the aim of the
      present study was to investigate in vivo whether the antiallergic effects of IL
      12 are mediated through IL-10. METHODS: C57BL/6J-IL-10 knock-out (IL-10(-/-))
      mice were sensitized intraperitoneally to ovalbumin (OVA) and subsequently
      exposed from day 14 to day 21 to aerosolized OVA (1%). IL-12 was administered
      intraperitoneally during sensitization, subsequent OVA exposure, or both.
      RESULTS: IL-12 inhibited the OVA-induced airway eosinophilia, despite the absence
      of IL-10. Moreover, a shift from a TH2 inflammatory pattern toward a TH1 reaction
      was observed, with concomitant pronounced mononuclear peribronchial inflammation
      after IL-12 treatment. Allergen-specific IgE synthesis was completely suppressed
      only when IL-12 was administered along with the allergen sensitization.
      Furthermore, treating the animals with IL-12 at the time of the secondary
      allergen challenge resulted not only in a significant suppression of the airway
      responsiveness but also in an important IFN-gamma-associated toxicity.
      CONCLUSIONS: These results indicate that IL-12 is able to inhibit allergen
      induced airway changes, even in the absence of IL-10. In addition, our results
      raise concerns regarding the redirection of TH2 inflammation by TH1-inducing
      therapies because treatment with IL-12 resulted not only in a disappearance of
      the TH2 inflammation but also in a TH1-driven inflammatory pulmonary pathology.

PMID- 11240950
TI  - Enhanced production of leukotrienes by peripheral leukocytes and specific IgE
      antibodies in patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: How leukotrienes (LTs) and IgE-mediated allergy reflect clinical
      features in patients with chronic obstructive pulmonary disease (COPD) remains
      unclear. OBJECTIVE: Our goal was to determine whether LTB4 and LTC4 would
      correlate with airway obstruction and whether IgE-mediated allergy would
      influence the generation of LTs and bronchial hyperresponsiveness in patients
      with COPD. METHODS: We measured the pulmonary function, methacholine bronchial
      hyperresponsiveness, and generation of LTB4 and LTC4 from peripheral leukocytes
      stimulated with calcium ionophore A23187 in relation to the presence of specific
      IgE antibodies against inhalant allergens. RESULTS: The leukocytes of patients
      with COPD generated significantly more LTB4 (with allergy, P <.001; without
      allergy, P <.001) and LTC4 (with allergy, P <.001; without allergy, P <.01) than
      the leukocytes of the control subjects. LTC4 production was significantly higher
      in the allergic COPD subjects than in the nonallergic COPD patients (P <.01), but
      the amount of LTB4 generated was not significantly different. FEV(1)
      significantly correlated with the level of both LTB4 (with allergy, r = -0.556, P
      =.0375; without allergy, r = -0.731, P =.0046) and LTC4 (with allergy, r = 
      0.764, P =.0043; without allergy, r = -0.526, P =.0414) generation in COPD. The
      log(10) of the minimum dose of methacholine was significantly higher in COPD
      patients without allergy than in those with allergy (P <.05). CONCLUSION:
      Enhanced LT generation from peripheral leukocytes is observed in patients with
      COPD, and the presence of specific IgE antibodies against inhalant allergens
      enhances LTC4 generation, bronchial hyperresponsiveness, and the relationship
      between LTC4 generation and airway obstruction.

PMID- 11240951
TI  - Association of IFN-gamma and IFN regulatory factor 1 polymorphisms with childhood
      atopic asthma.
AB  - BACKGROUND: IFN-gamma and related molecules play important roles in the
      differentiation and function of TH2 cells. OBJECTIVE: We sought to determine
      whether IFNG and related genes contribute to any susceptibility to atopic asthma,
      a representative TH2-dominant disorder. METHODS: We investigated the association
      of IFNG (CA repeat polymorphism within the first intron), IRF1 (GT repeat
      polymorphism within the intron 7), IFNGR1 (Val 14 Met), and IFNGR2 (Gln 64 Arg)
      gene polymorphisms with atopic asthma in the Japanese child population. RESULTS:
      A significant association (P =.0018) was observed between IFNG gene polymorphism
      and atopic asthma. The tendency was more prominent in patients with age of onset
      of 3 years or younger (P =.0004) or patients with a family history of allergic
      diseases (P =.0038). Furthermore, there was a significant association between
      IRF1 gene whole-allele distribution and atopic asthma (P =.044). The tendency was
      more prominent in patients with onset at 3 years of age or less (P =.0058). On
      the other hand, IFNGR1 and IFNGR2 gene polymorphisms showed no association with
      atopic asthma. CONCLUSION: These results suggested that among IFNG and related
      genes, IFNG and IRF1 genes confer genetic susceptibility to atopic asthma in
      Japanese children.

PMID- 11240952
TI  - Differences in proliferation of the hematopoietic cell line TF-1 and cytokine
      production by peripheral blood leukocytes induced by 2 naturally occurring forms
      of human IL-3.
AB  - BACKGROUND: A naturally occurring polymorphism in the coding region of the human
      IL3 gene leads to a change in amino acid residue 8 from proline to serine.
      OBJECTIVE: We sought to determine whether the 2 different forms of IL-3 varied in
      function. These different forms are available as recombinant proteins
      (recombinant human IL-3/proline 8 [rhIL-3/P8] and recombinant human IL-3/serine 8
      [rhIL-3/S8]). METHODS: The erythroleukemic cell line TF-1 was incubated with
      varying concentrations of rhIL-3/P8 or rhIL-3/S8 to determine the capacity of
      each type of IL-3 to induce proliferation. Human leukocytes were primed with rhIL
      3/P8 or rhIL-3/S8 for up to 24 hours and then stimulated with anti-IgE and
      assessed for leukotrienes (LTs), IL-4, and TNF-alpha. RESULTS: Proliferation of
      TF-1 cells was induced by both forms of IL-3 at 48 and 72 hours but to a greater
      degree by rhIL-3/P8. In contrast, the mean fold increase over control values of
      LT and IL-4 production was higher after priming the cells with rhIL-3/S8 versus
      rhIL-3/P8. Additionally, TNF-alpha production was greater (and reached
      significance only) for rhIL-3/S8. This activity was independent of IgE and thus
      directly stimulated by IL-3. Studies with basophil-enriched and basophil-depleted
      cell preparations revealed that LT production was evident only from the former
      and TNF-alpha only from the latter. CONCLUSION: We conclude that the 2 naturally
      occurring forms of human IL-3 have similar spectra of activities on cells with IL
      3 receptors, but the 2 forms have reversed relative efficacies for promoting
      proliferation (rhIL-3/P8 > rhIL-3/S8) compared with priming or inducing mediator
      secretion (rhIL-3/S8 > rhIL-3/P8).

PMID- 11240953
TI  - Cross-reactivity studies of a new group 2 allergen from the dust mite Glycyphagus
      domesticus, Gly d 2, and group 2 allergens from Dermatophagoides pteronyssinus,
      Lepidoglyphus destructor, and Tyrophagus putrescentiae with recombinant
      allergens.
AB  - BACKGROUND: Dust mites are important inducers of allergic disease. Group 2
      allergens are recognized as major allergens in several mite species, including
      Dermatophagoides pteronyssinus, Lepidoglyphus destructor, and Tyrophagus
      putrescentiae. No allergens have thus far been characterized on the molecular
      level from the dust mite Glycyphagus domesticus. OBJECTIVE: We sought to examine
      the cross-reactivity among group 2 allergens of G domesticus, L destructor, T
      putrescentiae, and D pteronyssinus. METHODS: A group 2 allergen from G
      domesticus, Gly d 2, was cloned and expressed as a recombinant protein. Cross
      reactivity between Gly d 2 and 3 other group 2 allergens, Lep d 2, Tyr p 2, and
      Der p 2, was studied by using individual sera and a serum pool RAST-positive to G
      domesticus, L destructor, T putrescentiae, and D pteronyssinus. Recombinant
      allergens were used as inhibitors of IgE binding in immunoblotting experiments.
      Molecular modeling on the basis of the Der p 2 structure was carried out for Gly
      d 2, Lep d 2, and Tyr p 2. RESULTS: Two cDNAs encoding isoforms of Gly d 2 were
      isolated, but only the Gly d 2.02 isoform was used in this study. Sixteen of 17
      subjects had IgE to Gly d 2. The protein sequence of Gly d 2 revealed 79%
      identity to Lep d 2 and 46% and 41% identity to Tyr p 2 and Der p 2,
      respectively. Extensive cross-reactivity was demonstrated among Gly d 2, Lep d 2,
      and Tyr p 2, but little cross-reactivity was found between these allergens and
      Der p 2. According to the tertiary structure of Der p 2 and 3-dimensional models
      of Gly d 2, Lep d 2, and Tyr p 2, differences reside mainly in surface-exposed
      residues. CONCLUSION: Gly d 2 showed high sequence homology to Lep d 2. Cross
      reactivity was observed between Gly d 2, Lep d 2, and Tyr p 2, but only limited
      cross-reactivity was demonstrated between these 3 allergens and Der p 2.

PMID- 11240954
TI  - Topical tacrolimus (FK506) leads to profound phenotypic and functional
      alterations of epidermal antigen-presenting dendritic cells in atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease in
      which antigen-presenting epidermal dendritic cells (DCs), ie, Langerhans cells
      and the so-called inflammatory dendritic epidermal cells (IDECs) expressing the
      high-affinity receptor for IgE (FcepsilonRI) may play a significant
      pathophysiologic role. Therapeutic efficacy of the immunosuppressive macrolide
      tacrolimus (FK506) in AD has been demonstrated in clinical trials, but little is
      known of its mode of action. OBJECTIVE: The present study focused on the effects
      of topical tacrolimus treatment on epidermal CD1a+/FcepsilonRI+ DC populations in
      lesional AD. METHODS: Immunohistological analysis, epidermal DC phenotyping, and
      functional studies were performed on skin biopsy specimens from treated and
      untreated lesional skin of 10 patients with AD participating in a clinical trial
      with tacrolimus. RESULTS: Untreated lesional skin was characterized by a high
      proportion of CD1a+ cells, which was largely due to a high proportion of IDECs
      strongly expressing FcepsilonRI. Epidermal DCs isolated from untreated lesional
      skin exhibited high stimulatory activity toward autologous T cells, which was
      strongly reduced while clinical improvement was seen during application of
      tacrolimus. Concomitantly, a decreased FcepsilonRI expression was observed in
      both Langerhans cells and IDECs. Finally, topical tacrolimus led to a progressive
      decrease in the IDEC population within the pool of CD1a+ epidermal DCs and also
      to a decrease in their CD36 expression, which is indicative of lower local
      inflammation. CONCLUSION: Epidermal CD1a+ DCs may represent a target for topical
      tacrolimus in the treatment of AD.

PMID- 11240955
TI  - Skin concentrations of H1-receptor antagonists.
AB  - BACKGROUND: H1-receptor antagonists are widely used in the treatment of allergic
      skin disorders. OBJECTIVE: We sought to evaluate the extent of fexofenadine and
      diphenhydramine distribution into the skin concomitantly with their peripheral H1
      receptor antagonist activity. METHODS: In a prospective, randomized, double
      blind, parallel-group study, 7 men received 120 mg of fexofenadine, and 7
      received 50 mg of diphenhydramine. Before dosing; at 1, 3, 6, 9, and 24 hours
      after the first dose; and at 168 hours (steady-state), 12 hours after the seventh
      and last daily dose, blood samples and skin punch biopsy specimens were obtained,
      and epicutaneous tests with histamine phosphate, 1 mg/mL, were performed.
      RESULTS: Fexofenadine penetrated the skin to a significantly greater extent than
      diphenhydramine at 6, 9, 24, and 168 hours (P < or = .05). Maximum skin/plasma
      ratios of both the H1-antagonists (41.3 +/- 7.8 for fexofenadine and 8.1 +/- 4.4
      for diphenhydramine) were obtained at 24 hours. Fexofenadine also produced
      significantly greater suppression of wheals at 3, 6, and 9 hours and of flares at
      3, 6, 9, and 168 hours compared with diphenhydramine (P < or = .05). CONCLUSION:
      In disorders in which the presence and the effects of H1-receptor antagonists in
      the skin are clinically relevant, our results support the use of fexofenadine and
      indicate the need to re-examine the role of diphenhydramine.

PMID- 11240956
TI  - Intradermal administration of a killed Mycobacterium vaccae suspension (SRL 172)
      is associated with improvement in atopic dermatitis in children with moderate-to
      severe disease.
AB  - BACKGROUND: Although a doubling in the prevalence of atopic disease, including
      atopic dermatitis, in the Western world over the last few generations has been
      paralleled by a marked reduction in infectious diseases, especially tuberculosis,
      it is unclear whether this increase in atopy is causally related to reduced
      exposure to mycobacteria. OBJECTIVES: The aim of this study was to determine
      whether administration of mycobacterial antigens to atopic individuals might
      ameliorate their disease. METHODS: Forty-one children aged 5 to 18 years with
      moderate-to-severe atopic dermatitis were enrolled in a randomized, double-blind,
      placebo-controlled trial, where they were given either one intradermal injection
      of killed Mycobacterium vaccae (SRL 172) or buffer solution (placebo). Changes in
      skin surface area affected by dermatitis and dermatitis severity score were
      assessed before treatment and at 1 and 3 months after treatment. RESULTS:
      Children treated with SRL 172 showed a mean 48% (95% CI, 32%-65%) reduction in
      surface area affected by dermatitis compared with a mean 4% (95% CI, -29% to 22%)
      reduction for the placebo group (P <.001) and a median 68% (interquartile range,
      46%-85%) reduction in dermatitis severity score compared with 18% (interquartile
      range, -2% to 34%) for the placebo group (P <.01) at 3 months after treatment.
      There were no untoward effects of the treatment, apart from a local reaction in
      13 of the 21 children, which occurred 1 month after SRL 172 administration and
      settled spontaneously. CONCLUSION: SRL 172 was associated with an improvement in
      the severity of the dermatitis in children with moderate-to-severe disease.

PMID- 11240957
TI  - Thymus and activation-regulated chemokine in atopic dermatitis: Serum thymus and
      activation-regulated chemokine level is closely related with disease activity.
AB  - BACKGROUND: Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin
      disease characterized by the predominant infiltration of TH2-type cells in
      lesional skin. Thymus and activation-regulated chemokine (TARC/CCL17) is a
      chemokine that attracts CC chemokine receptor 4-positive (CCR4+) or CCR8+ cells.
      OBJECTIVE: The purpose of this study was to investigate the participation of TARC
      in AD. METHODS: We measured serum TARC levels in 40 patients with AD, 20 healthy
      control subjects, and 20 patients with psoriasis. We also examined disease
      activity by using SCORAD score; serum soluble E-selectin, soluble IL-2 receptor,
      IgE, and GM-CSF levels; and eosinophil numbers in peripheral blood, as well as
      correlations between TARC levels and these factors. The positivity of CCR4 of
      CD4+CD45RO+ cells in PBMCs was examined by using FACS analysis.
      Immunohistochemical staining of TARC and GM-CSF was performed in the lesional
      skin of patients with AD. RESULTS: The serum TARC levels of patients with AD were
      significantly higher than those of healthy control subjects and patients with
      psoriasis. The serum TARC levels significantly correlated with eosinophil number
      (r = 0.61), SCORAD score (r = 0.60), and serum soluble E-selectin levels (r =
      0.58) and weakly correlated with serum soluble IL-2 receptor levels (r = 0.34) in
      patients with AD. The TARC levels of patients with AD decreased after the
      treatment in accordance with the improvement of clinical symptoms. The CCR4
      positivity of CD4+CD45RO+ cells in PBMCs of patients with AD was also higher than
      that of healthy control subjects. Immunohistochemical staining revealed that TARC
      was positive in keratinocytes in the epidermis and in vascular endothelial cells,
      T cells, and dendritic cells in the dermis. CONCLUSION: Serum TARC levels are
      associated with disease activity of AD, and TARC may play an important role in
      the pathogenesis of AD.

PMID- 11240959
TI  - Atopy patch tests, together with determination of specific IgE levels, reduce the
      need for oral food challenges in children with atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis is commonly associated with food allergy. In
      addition to skin prick tests (SPTs) and measurements of specific IgE levels, the
      atopy patch test (APT) has recently been introduced into the diagnostic procedure
      for food allergy. OBJECTIVE: Our aim was to evaluate whether a combination of
      allergologic tests could improve the prognostic value of the individual tests for
      positive food challenge results. We hypothesized that the combination of a
      positive APT result plus proof of specific IgE, a positive SPT result, or both
      would render double-blind, placebo-controlled, food challenges unnecessary.
      METHODS: One hundred seventy-three double-blind, placebo-controlled, food
      challenges were performed in 98 children (median age, 13 months) with atopic
      dermatitis. All children were subjected to SPTs, APTs, and determination of
      specific IgE. Sensitivity, specificity, and positive and negative predictive
      values were calculated. RESULTS: Ninety-five (55%) of 173 oral provocations were
      assessed as positive. For evaluating suspected cow's milk (CM) allergy, the APT
      was the best single predictive test (positive predictive value [PPV], 95%), and
      the combination of a positive APT result with evidence of specific IgE or an APT
      result together with a positive skin prick test response optimized the PPV to
      100%. For hen's egg (HE) allergy, the APT was also the best single predictive
      test (PPV, 94%). The combination of 2 or more tests did not exceed the APT's
      predictive value. In both CM and HE challenges, the predictability of oral
      challenges depended on the level of specific IgE. For wheat allergy, the APT
      proved to be the most reliable test, and the PPV of 94% could not be improved by
      a combination with other allergologic tests. CONCLUSION: The combination of
      positive APT results and measurement of levels of specific IgE (CM, > or = 0.35
      kU/L; HE, > or = 17.5 kU/L) makes double-blind, placebo-controlled, food
      challenges superfluous for suspected CM and HE allergy.

PMID- 11240958
TI  - Occupational asthma in symptomatic workers exposed to natural rubber latex:
      evaluation of diagnostic procedures.
AB  - BACKGROUND: Natural rubber latex (NRL) has been increasingly identified as a
      cause of occupational asthma (OA). OBJECTIVE: We sought to examine the accuracy
      of the clinical history, immunologic tests, and assessment of nonspecific
      bronchial hyperresponsiveness in diagnosing OA caused by latex compared with that
      of the specific inhalation challenge (SIC). METHODS: Forty-five consecutive
      patients referred for investigation of possible OA caused by latex underwent a
      diagnostic protocol, including an open medical questionnaire, skin prick testing
      against latex, measurement of bronchial responsiveness to histamine, and
      inhalation challenge with latex gloves. Recorded clinical history was judged
      retrospectively by 4 physicians who were blinded for the results of other
      objective tests. RESULTS: The clinical history, skin prick testing against NRL,
      and assessment of nonspecific bronchial hyperresponsiveness showed a high
      sensitivity (87%, 100%, and 90%, respectively) but a low specificity (14%, 21%,
      and 7%, respectively) when compared with the results of the SIC. Logistic
      regression analysis showed that combining the results of skin prick tests against
      latex with the clinical history enhanced the negative predictive value from 50%
      to 71%, whereas the positive predictive value remained virtually unchanged (75%
      vs 76%). CONCLUSION: The clinical history and immunologic tests were the most
      useful procedures in diagnosing NRL-induced asthma, although combining the 2
      procedures remained less accurate than SIC. Further examination of the predictive
      values of available tests is warranted to recommend diagnostic strategies that
      are specific to the various agents causing OA.

PMID- 11240960
TI  - Occupational asthma caused by IgE-mediated reactivity to Antiaris wood dust.

PMID- 11240962
TI  - Anaphylaxis to oxybenzone, a frequent constituent of sunscreens.

PMID- 11240961
TI  - Human skin mast cells adhere to vitronectin via the alphavbeta3 integrin receptor
      (CD51/CD61).

PMID- 11240963
TI  - Selective severe anaphylactic reaction due to ketorolac tromethamine without
      nonsteroidal anti-inflammatory drug intolerance.

PMID- 11240964
TI  - Fatal latex allergy.

PMID- 11240965
TI  - Peanut allergy: children who lose the positive skin test response.

PMID- 11240966
TI  - In vitro allergy testing.

PMID- 11240968
TI  - Leukotriene C4 synthase polymorphism and aspirin-induced asthma.

PMID- 11240971
TI  - Biomarkers and surrogate endpoints: preferred definitions and conceptual
      framework.

PMID- 11240972
TI  - Loratadine and terfenadine interaction with nefazodone: Both antihistamines are
      associated with QTc prolongation.
AB  - BACKGROUND AND OBJECTIVE: Nefazodone inhibits CYP3A; therefore coadministration
      with CYP3A substrates such as terfenadine or loratadine may result in increased
      exposure to these drugs. A potential pharmacodynamic consequence is
      electrocardiographic QTc prolongation, which has been associated with torsade de
      pointes cardiac arrhythmia. Therefore a clinical pharmacokinetic-pharmacodynamic
      evaluation of this potential interaction was conducted. METHODS: A randomized,
      double-blind, double-dummy, parallel group, multiple-dose design was used.
      Healthy men and women who were given doses of 60 mg of terfenadine every 12
      hours, 20 mg of loratadine once daily, and 300 mg of nefazodone every 12 hours
      were studied. Descriptive pharmacokinetics (time to maximum concentration,
      maximum concentration, and area under the plasma concentration-time curve) were
      used for the examination of interactions among the respective parent drugs and
      metabolites. QTc prolongation (mean value over the dosing interval) was the
      pharmacodynamic parameter measured. Kinetic and dynamic analysis was used for the
      examination of pooled concentration and QTc data with the use of a linear model.
      RESULTS: Concomitant nefazodone treatment markedly increased the dose interval
      area under the plasma concentration-time curve of both terfenadine (mean value,
      17.3 +/- 8.5 ng. mL/h versus 97.4 +/- 48.9 ng. mL/h; P <.001) and
      carboxyterfenadine (mean value, 1.69 +/- 0.48 microg. h/mL versus 2.88 +/- 0.53
      microg. h/mL; P <.001) and moderately increased the dose interval area under the
      plasma concentration-time curve of both loratadine (mean value, 31.5 +/- 27.9 ng.
      h/mL versus 43.7 +/- 25.9 ng. h/mL; P <.014) and descarboethoxyloratadine (mean
      value, 73.4 +/- 54.9 ng. h/mL versus 81.9 +/- 26.2 ng. h/mL; P <.002). The mean
      QTc was unchanged with terfenadine alone; however, it was markedly prolonged with
      concomitant nefazodone and terfenadine (mean [90% confidence interval]
      prolongation 42.4 ms [34.2, 50.6 ms]; P <.05). Similarly, the mean QTc was
      unchanged with loratadine alone; however, it was prolonged with concomitant
      nefazodone and loratadine (21.6 ms [13.7, 29.4 ms]; P <.05). Nefazodone alone did
      not change mean QTc. QTc was positively correlated with terfenadine plasma
      concentration (r (2) = 0.21; P =.0001). Similarly, QTc was positively correlated
      with loratadine plasma concentration (r (2) = 0.056; P =.0008) but with a flatter
      slope. There was no relationship between QTc and nefazodone plasma concentration
      during treatment with nefazodone alone (r (2) = 0.002, not significant).
      CONCLUSIONS: In healthy men and women, concomitant nefazodone treatment at a
      therapeutic dose increases exposure to both terfenadine and carboxyterfenadine.
      This increased exposure is associated with marked QTc prolongation, which is
      correlated with terfenadine plasma concentration. A similar interaction occurs
      with loratadine, although it is of lesser magnitude. Concomitant administration
      of nefazodone with terfenadine may have predisposed individuals to the arrhythmia
      associated with QTc prolongation, torsade de pointes, when terfenadine was
      available for clinical use. However, a new finding is that in the context of
      higher than clinically recommended daily doses (20 mg) of loratadine concomitant
      administration with a metabolic inhibitor such as nefazodone can also result in
      QTc prolongation.

PMID- 11240973
TI  - Effect of fluvoxamine on the pharmacokinetics of mexiletine in healthy Japanese
      men.
AB  - BACKGROUND AND OBJECTIVES: Fluvoxamine, a selective serotonin reuptake inhibitor,
      is known to inhibit several hepatic cytochrome P450 (CYP) isozymes, in particular
      CYP1A2. Mexiletine is mainly catalyzed by CYP2D6 and partially catalyzed by
      CYP1A2. Our objective was to study the potential pharmacokinetic interaction
      between fluvoxamine and mexiletine. METHODS: A randomized crossover design with
      two phases was used. A 7-day washout period separated the two treatment
      conditions. In the one phase, 6 healthy Japanese men received an oral dose of 200
      mg of mexiletine alone (study 1); in the other phase, the men received
      fluvoxamine (50 mg twice a day) for 7 days, and on the eighth day they received
      oral mexiletine (200 mg) and fluvoxamine concomitantly (study 2). The
      concentrations of mexiletine were measured with HPLC. RESULTS: The area under the
      concentration-time curve and serum peak concentration of mexiletine in study 2
      were significantly increased compared with those in study 1 (10.4 +/- 4.85 versus
      6.70 +/- 3.21 microg x h/mL, P =.006 and 0.623 +/- 0.133 versus 0.536 +/- 0.164
      microg/mL, P =.008, respectively). CONCLUSION: The effect of fluvoxamine on the
      mexiletine disposition is comparatively large, and when mexiletine and
      fluvoxamine are coadministered careful monitoring of mexiletine is needed.

PMID- 11240974
TI  - Stereoselective pharmacokinetics of pantoprazole, a proton pump inhibitor, in
      extensive and poor metabolizers of S-mephenytoin.
AB  - Pantoprazole, a proton pump inhibitor, is administered as a racemic mixture. To
      determine the role of cytochrome P450 (CYP) 2C19 in the stereoselective
      metabolism of pantoprazole, we investigated the pharmacokinetic disposition of
      (+)- and (-)-pantoprazole in 7 extensive metabolizers and 7 poor metabolizers of
      S-mephenytoin. All of the subjects received an oral 40-mg dose of racemic
      pantoprazole as the enteric-coated formulation. In the extensive metabolizers,
      the mean clearance of (-)-pantoprazole was only slightly lower than that of (+)
      pantoprazole and no significant differences in the other pharmacokinetic
      parameters between (+)- and (-)-pantoprazole were observed. The mean (+)/(-)
      ratios for maximum concentration, area under the plasma concentration-time curve
      from 0 to infinity, and elimination half-life were 0.94, 0.82, and 0.90,
      respectively. In contrast, in the poor metabolizers, the clearance values of both
      enantiomers were significantly lower than those in the extensive metabolizers,
      and a significant difference in pharmacokinetics between (+)- and (-)
      pantoprazole was observed. The mean elimination half-life for (+)-pantoprazole
      was 3.55-fold longer than that of (-)-pantoprazole, and the mean maximum
      concentration and area under the plasma concentration-time curve from 0 to
      infinity for (+)-pantoprazole were 1.31- and 3.59-fold greater, respectively,
      than those for (-)-pantoprazole. These results indicate that the stereoselective
      metabolism of pantoprazole depends on S-mephenytoin 4'-hydroxylase (CYP2C19). The
      metabolism of (+)-pantoprazole was impaired to a greater extent than (-)
      pantoprazole in the poor metabolizers.

PMID- 11240975
TI  - The effect of rifampin administration on the disposition of fexofenadine.
AB  - OBJECTIVE: Our objective was to assess the effect of rifampin (INN, rifampicin)
      on the pharmacokinetics of fexofenadine and to assess the influence of advanced
      age and sex. METHODS: Twelve young volunteers (6 men and 6 women; age range, 22
      to 35 years) and twelve elderly volunteers (6 men and 6 women; age range, 65 to
      76 years) received a 60-mg oral dose of fexofenadine before and after treatment
      with 600 mg of oral rifampin for 6 days. Blood and urine were collected for 48
      hours and assayed for fexofenadine, azacyclonol, and rifampin by HPLC with either
      fluorescence or mass spectrometry detection. RESULTS: All of the groups had a
      significant increase (P <.05) in the oral clearance of fexofenadine after
      rifampin treatment: young men, 2955 +/- 1516 versus 5524 +/- 3410 mL/min; young
      women, 2632 +/- 996 versus 7091 +/- 5,379 mL/min; elderly men, 1760 +/- 850
      versus 4608 +/- 1159 mL/min; and elderly women, 2210 +/- 554 versus 4845 +/- 1600
      mL/min. The peak serum concentration of fexofenadine was also significantly
      reduced (P <.05) by rifampin treatment: young men, 77 +/- 31 versus 52 +/- 17
      ng/mL; young women, 72 +/- 19 versus 36 +/- 14 ng/mL; elderly men, 106 +/- 42
      versus 52 +/- 14 ng/mL; elderly women, 76 +/- 23 versus 46 +/- 19 ng/mL. Half
      life (150 to 230 minutes), time to maximum concentration (130 to 205 minutes),
      renal clearance (95 to 153 mL/min), and fraction unbound (2.9% to 3.7%) of
      fexofenadine showed no significant difference between control and treatment. The
      amount of azacyclonol, a CYP3A4 mediated metabolite of fexofenadine, eliminated
      renally increased on average 2-fold after rifampin dosing; however, this pathway
      accounted for less than 0.5% of the dose. No effect of age or sex on fexofenadine
      disposition or serum trough rifampin concentration (0.2 microg/mL to 1.8
      microg/mL) was observed before or after rifampin treatment. CONCLUSION: This
      study showed that rifampin effectively increased fexofenadine oral clearance and
      that this effect was independent of age and sex. We conclude that the cause of
      the increased oral clearance of fexofenadine is a reduced bioavailability caused
      by induction of intestinal P-glycoprotein.

PMID- 11240976
TI  - Comparison of sympathetic modulation induced by single oral doses of mibefradil,
      amlodipine, and nifedipine in healthy volunteers.
AB  - OBJECTIVE: Our objective was to compare the sympathetic modulation induced by
      oral administration of a single dose of 20 mg of standard nifedipine, of 10 mg of
      amlodipine, and of 100 mg of mibefradil. METHODS: Sixteen healthy male volunteers
      participated in this double-blind, randomized, placebo-controlled, crossover four
      period study. The sympathetic modulation induced by treatments was evaluated
      during 24 hours after drug administration by neurohormonal dosages, hemodynamic
      parameter measurements, and spectral analysis of heart rate and blood pressure.
      RESULTS: We observed a significant (P <.05) decrease in diastolic blood pressure
      1 hour after the administration of nifedipine (62 +/- 9 to 59 +/- 5 mm Hg) with
      concomitant increases in heart rate (59 +/- 5 to 74 +/- 8 bpm) and neurohormones
      (53 +/- 18 to 83 +/- 50 pg/mL for aldosterone, 157 +/- 56 to 282 +/- 119 pg/mL
      for norepinephrine, and 9.8 +/- 5.5 to 40.2 +/- 97.1 pg/mL for active renin). No
      significant modification of these parameters was observed with amlodipine and
      mibefradil, except an isolated increase of norepinephrine plasma level 2 hours
      after the administration of mibefradil (133.1 +/- 67.1 to 210.9 +/- 92.5 pg/mL).
      The spectral analysis over 24 hours of Mayer waves of systolic blood pressure did
      not show any significant change over time in the different groups. When the
      analysis was performed during the first 4 hours after treatment administration,
      we observed a decrease of Mayer waves of systolic blood pressure with nifedipine
      (2.21 +/- 1.45 mm Hg(2) versus 3.53 +/- 1.85 mm Hg(2) with placebo). These
      results indicate that oral single doses of mibefradil and amlodipine do not
      induce baroreflex-mediated clinical changes in healthy volunteers. The single
      oral dose of nifedipine resulted in a marked increase in sympathetic tone and a
      decrease in systolic blood pressure variability early after oral administration.
      CONCLUSION: Mibefradil, the nondihydropyridine calcium antagonist, exerts much
      less sympathetic stimulation than nifedipine.

PMID- 11240977
TI  - Effect of angiotensin II on venodilator response to nitroglycerin.
AB  - OBJECTIVE: An enhanced circulatory angiotensin II level that results from the
      administration of nitroglycerin may contribute to the development of nitrate
      tolerance. Using human hand veins, we investigated whether a subconstricting dose
      of angiotensin II attenuates the venodilator effect of nitroglycerin, whether
      pretreatment with losartan influences this effect, and whether angiotensin II
      also attenuates the venodilator effect of diltiazem. METHODS: In 9 healthy male
      subjects, increasing doses (0.5-128 ng/min) of nitroglycerin were infused into
      the dorsal hand vein pretreated with 0 (control), 0.3, or 1 ng/min of angiotensin
      II. In 8 healthy male subjects, angiotensin II (0.3 and 1 ng/min) was infused
      into the vein dilated by nitroglycerin with and without pretreatment with
      losartan and with diltiazem. The diameter of the vein was measured with a linear
      variable differential transformer. RESULTS: The venodilator response of
      nitroglycerin was significantly suppressed by the pretreatment with angiotensin
      II; The maximum venodilator effect was dose-dependently decreased, and the
      infusion rate producing half-maximum response was dose-dependently increased. The
      venodilation caused by nitroglycerin was decreased by angiotensin II, and this
      effect was attenuated by pretreatment with losartan. The venodilation caused by
      diltiazem was also attenuated by angiotensin II, but this attenuating effect was
      smaller compared with that caused by nitroglycerin. CONCLUSIONS: These findings
      suggest that an enhanced angiotensin II level might attenuate the venodilation
      caused by nitroglycerin and diltiazem, and pretreatment with losartan might
      decrease the attenuating effect of angiotensin II.

PMID- 11240978
TI  - Effect of mycophenolate mofetil therapy on inosine monophosphate dehydrogenase
      induction in red blood cells of heart transplant recipients.
AB  - BACKGROUND: Mycophenolic acid is reported to provide effective immunosuppression
      by inhibiting inosine monophosphate dehydrogenase. In an attempt to monitor the
      biological effects of long-term therapy with mycophenolate mofetil, we measured
      levels of guanosine 5' triphosphate and adenosine 5' triphosphate in red blood
      cells (RBCs) of patients after heart transplantations. METHODS: Fifty-two
      patients enrolled in the study were randomly assigned to one of two groups.
      Patients in the control group (n = 27) received cyclosporine A (INN,
      ciclosporin), azathioprine, and prednisone. Patients in the study group (n = 25)
      were switched from azathioprine to mycophenolate mofetil 3 months after the heart
      transplantation. Adenosine 5' triphosphate and guanosine 5' triphosphate levels
      were determined by means of HPLC. The activities of inosine monophosphate
      dehydrogenase and hypoxanthine-guanine phosphoribosyltransferase, which are
      responsible for guanine nucleotide formation, were measured in RBCs by
      radiochemical methods. RESULTS: Adenosine 5' triphosphate levels were unchanged
      in patients treated with mycophenolate mofetil, whereas those of the control
      group who received azathioprine (from 142 +/- 26 pmol/10(6) RBCs to 165 +/- 25
      pmol/10(6) RBCs; P <.001) increased. As the length of mycophenolate mofetil
      therapy increased, patients in the study group showed significantly elevated
      guanosine 5' triphosphate levels (15.6 +/- 6.1 pmol/10(6) RBCs versus 6.6 +/- 2.1
      pmol/10(6) RBCs; P <.001) and a 5-fold increase in inosine monophosphate
      dehydrogenase activity (108.6 +/- 13.3 pmol/mg of protein per hour versus 22.5 +/
      1.7 pmol/mg of protein per hour; P <.001) compared with the control group. In
      addition, a slight but significant enhancement of hypoxanthine-guanine
      phosphoribosyltransferase activity was seen in the mycophenolate mofetil group.
      CONCLUSIONS: Our studies have shown that long-term administration of
      mycophenolate mofetil is associated with increasing guanosine 5' triphosphate
      levels in RBCs as the result of an induction of inosine monophosphate
      dehydrogenase and hypoxanthine-guanine phosphoribosyltransferase activities in
      erythrocytes.

PMID- 11240979
TI  - Pharmacokinetics and pharmacodynamics of sotalol in a pediatric population with
      supraventricular and ventricular tachyarrhythmia.
AB  - OBJECTIVE: This pharmacokinetic-pharmacodynamic study was designed to define the
      steady-state relationship between pharmacologic response and dose or
      concentration of sotalol in children with cardiac arrhythmias, with an emphasis
      on neonates and infants. METHODS: The treatment consisted of an upward titration
      with unit doses of 10, 30, and 70 mg of sotalol per square meter of body surface
      area. The patients received 3 doses at each dose level. The dosing interval was 8
      hours. The Class III and beta-blocking activities of sotalol were derived from
      the QT and R-R intervals, respectively, of the surface electrocardiogram, which
      was recorded at 6 scheduled times before and after the third, sixth, and ninth
      doses. During these three dose intervals, 4 scheduled blood samples were also
      collected. Drug concentrations were measured with a validated nonstereoselective
      liquid chromatographic tandem mass spectrometric detection assay. Pharmacokinetic
      and pharmacodynamic parameters were obtained with standard methods. RESULTS:
      Twenty-one centers enrolled 25 patients in the study: 7 were neonates, 9 were
      infants, and 11 were children between the ages of 2 years and 12 years. The area
      under the drug concentration-time curve increased proportionately with dose. The
      apparent oral clearance of sotalol was linearly correlated with body surface area
      and creatinine clearance. The smallest children (body surface area <0.33 m2)
      displayed greater drug exposure than the larger children. The increase of QTc and
      R-R intervals was dose dependent. At the 70-mg/m(2) dose level, the mean (+/-
      standard deviation) maximum increase for the QTc interval was 14% +/- 7% and the
      average Class III effect during a dose interval was 7% +/- 5%. At the same dose
      level, the mean maximum increase of the R-R interval was 25% +/- 15% and the
      average beta-blocking effect during a dose interval was 12% +/- 13%. The effects
      tended to be larger in the smallest children. The Class III response and the
      plasma concentrations of sotalol were linearly related. The treatment was well
      tolerated. CONCLUSIONS: The steady-state pharmacokinetics of sotalol were dose
      proportionate. Pharmacologically important beta-blocking effects were observed at
      the 30-mg/m2 and 70-mg/m2 dose levels. Important Class III effects were seen at
      the 70-mg/m2 dose level. The Class III effect was linearly related to the drug
      concentration.

PMID- 11240980
TI  - Effect of genotypic differences in CYP2C19 on cure rates for Helicobacter pylori
      infection by triple therapy with a proton pump inhibitor, amoxicillin, and
      clarithromycin.
AB  - BACKGROUND: Proton pump inhibitors such as omeprazole and lansoprazole are mainly
      metabolized by CYP2C19 in the liver. The therapeutic effects of proton pump
      inhibitors are assumed to depend on CYP2C19 genotype status. OBJECTIVE: We
      investigated whether CYP2C19 genotype status was related to eradication rates of
      H pylori by triple proton pump inhibitor-clarithromycin-amoxicillin (INN,
      amoxicilline) therapy and attempted to establish a strategy for treatment after
      failure to eradicate H pylori. METHODS: A total of 261 patients infected with H
      pylori completed initial treatment with 20 mg of omeprazole or 30 mg of
      lansoprazole twice a day, 200 mg of clarithromycin three times a day, and 500 mg
      of amoxicillin three times a day for 1 week. CYP2C19 genotypes of patients were
      determined with polymerase chain reaction-restriction fragment length
      polymorphism analysis. Patients without eradication after initial treatment were
      retreated with 30 mg of lansoprazole four times daily and 500 mg of amoxicillin
      four times daily for 2 weeks. RESULTS: Eradication rates for H pylori were 72.7%
      (95% confidence interval, 64.4%-81.8%), 92.1% (confidence interval, 86.4%-97.3%),
      and 97.8% (confidence interval, 88.5%-99.9%) in the homozygous extensive,
      heterozygous extensive, and poor metabolizer groups, respectively. Thirty-four of
      35 patients without eradication had an extensive metabolizer genotype of CYP2C19.
      Nineteen of those patients were infected with clarithromycin-resistant strains of
      H pylori. However, there were no amoxicillin-resistant strains of H pylori. Re
      treatment of H pylori infection with dual high-dose lansoprazole-amoxicillin
      therapy succeeded in 30 of 31 patients with extensive metabolizer genotype of
      CYP2C19. CONCLUSION: The majority of patients without initial eradication of H
      pylori had an extensive metabolizer CYP2C19 genotype but were successfully re
      treated with high doses of lansoprazole and an antibiotic to which H pylori was
      sensitive, such as amoxicillin, even when the patients were infected with
      clarithromycin-resistant strains of H pylori.

PMID- 11240981
TI  - Frequency of single nucleotide polymorphisms in the P-glycoprotein drug
      transporter MDR1 gene in white subjects.
AB  - BACKGROUND: P-glycoprotein, the gene product of MDR1, confers multidrug
      resistance against antineoplastic agents but also plays an important role in the
      bioavailability of common drugs in medical treatment. Various polymorphisms in
      the MDR1 gene were recently identified. A silent mutation in exon 26 (C3435T) was
      correlated with intestinal P-glycoprotein expression and oral bioavailability of
      digoxin. OBJECTIVE: We wanted to establish easy-to-use and cost-effective
      genotyping assays for the major known MDR1 single nucleotide polymorphisms and
      study the allelic frequency distribution of the single nucleotide polymorphisms
      in a large sample of volunteers. METHODS: In this study, the distribution of the
      major MDR1 alleles was determined in 461 white volunteers with the use of
      polymerase chain reaction and restriction fragment length polymorphism. RESULTS:
      Five amino acid exchanges were found with allelic frequencies of 11.2% for
      Asn21Asp and 5.5% for Ser400Asn. Strikingly, in exon 21 three variants were
      discovered at the same locus: 2677G (56.4%), 2677T (41.6%), and 2677A (1.9%),
      coding for 893Ala, Ser, or Thr. A novel missense Gln1107Pro mutation was found in
      two cases (0.2%). The highest frequencies were observed for intronic and silent
      polymorphisms; C3435T occurred in 53.9% of the subjects heterozygously, and 28.6%
      of individuals were homozygous carriers of 3435T/T with functionally restrained P
      glycoprotein. CONCLUSION: This study provides the first analysis of MDR1 variant
      genotype distribution in a large sample of white subjects. It gives a basis for
      large-scale clinical investigations on the functional role of MDR1 allelic
      variants for bioavailability of a substantial number of drugs.

PMID- 11240982
TI  - Attitudes toward nicotine replacement therapy in smokers and ex-smokers in the
      general public.
AB  - OBJECTIVE: Nicotine replacement therapy (NRT) doubles the chances that a smoker
      will quit smoking, but most smokers who attempt to quit do not use it at all or
      only use it inconsistently. We aimed to identify attitudes of smokers and ex
      smokers toward NRT and to develop and assess the validity of a brief scale used
      to measure these attitudes. METHODS: We conducted a first mail survey of 256
      smokers and ex-smokers to collect qualitative data and to develop survey items
      and a second mail survey of 494 smokers and ex-smokers to finalize the scale and
      assess its validity. The study was conducted in Geneva, Switzerland, in 1998 to
      1999. RESULTS: The study resulted in a 2-dimensional, 12-item scale: the
      Attitudes Toward Nicotine Replacement Therapy scale (ANRT-12). The 2 subscales
      measure perception of the advantages of NRT (8 items) and the drawbacks of NRT (4
      items). Internal consistency coefficients (alpha = 0.84 and 0.75, respectively)
      and test-retest correlations (0.79 for both scales) were high. The scales
      respected criteria of content and construct validity. Scores were associated with
      intention to use NRT, and among those who had ever used NRT, with the number of
      days of use. A disturbing result was that only 1 (16%) of 6 participants agreed
      that "NRT helps people quit smoking," and only 1 (24%) of 4 ex-smokers had ever
      used NRT. CONCLUSIONS: Many smokers and ex-smokers have inadequate knowledge of
      and negative attitudes toward NRT. ANRT-12 is a valid and reliable measure of
      these attitudes; it can be used by clinicians, researchers, and educators to
      improve use of and compliance with NRT.

PMID- 11240983
TI  - Estrogen metabolism as a risk factor for head and neck cancer.
AB  - OBJECTIVE: Estrogen metabolites have been associated in the pathogenesis of
      breast and cervical cancer; 16alpha-hydroxyestrone(16alpha-OHE1) demonstrated
      proliferative effects whereas 2-hydroxyestrone(2-OHE1) had antiproliferative
      effects. Our study's objective is to demonstrate that head and neck (H&N) cancer
      patients metabolize estrogen differently than healthy controls, which may
      constitute a risk factor for H&N cancer development. STUDY DESIGN: Urinary
      metabolite levels of 2-OHE1 and 16alpha-OHE1 from 50 H&N cancer patients and 50
      age- and sex-matched controls were measured using enzyme-linked immunosorbent
      assay (ELISA). Absolute values and 2-/16alpha-OHE1 ratios were calculated.
      Conditional logistic regression for univariate and multivariate analysis with
      odds ratio (OR) and 95% confidence interval (CI) were used. RESULTS: Thirty
      percent (15 of 50) from the case group had a low 2-/16alpha-OHE1 ratio compared
      with only 4% (2 of 50) in the control group (OR = 11.1; 1.4-91.5, 95% CI) (P <
      0.05). When adjusted for tobacco, OR remained significant at 15.6 (1.1-212.5, 95%
      CI) (P < 0.05). CONCLUSION: H&N cancer patients are more likely to express
      abnormal estrogen metabolism than healthy controls; 2-/16alpha-OHE1 may serve as
      a potential biological marker of individuals at increased risk of H&N cancer.

PMID- 11240984
TI  - Skin metastases in squamous cell carcinoma of the head and neck.
AB  - Distant metastases in squamous cell carcinoma of the head and neck (SCCHN) are
      most often to the lung, liver, and bone. SCCHN rarely metastasizes to skin sites.
      OBJECTIVE: To ascertain the significance of skin metastases (SM) on the prognosis
      of patients with SCCHN. METHODS: A retrospective review of all patients between
      1987 and 1999 with SCCHN was conducted. Patients in whom SM developed were
      identified. Data pertaining to demographics, primary tumor staging, SM
      development, and outcome were investigated. RESULTS: In 798 consecutive patients
      diagnosed with SCCHN between 1987 and 2000, 19 developed SM. The average time of
      onset of the SM was 17.65 months. The average survival time was 7.2 months after
      the development of SM. The overall survival time of patients who developed SM
      from the initial presentation of the primary tumor was 24.85 months. The 1-year
      survival rate from the time of development of SM was 0%. CONCLUSIONS: Metastasis
      to skin sites is an uncommon feature of SCCHN. SM may represent the first
      clinical evidence of impending loco-regional recurrence or distant metastasis.
      The development of SM is an ominous sign associated with an extremely poor
      prognosis, similar to the development of distant metastasis at more typical
      sites. Both the development of SM and survival of patients developing SM are
      independent of primary tumor stage. Current treatment options of SM are limited
      in their efficacy.

PMID- 11240985
TI  - Occult lymph node metastases in supraglottic cancers of the larynx.
AB  - Occult cervical lymph node metastases may often be associated with cancers of the
      supraglottic larynx. The aims of this investigation were: (1) to determine the
      incidence of occult lymph node metastases in patients with cancer of the larynx;
      (2) to assess whether the presence of such metastases was related to the extent
      of the primary tumor (T) and its grading (G); and (3) to discuss which
      therapeutic approach should be followed in treating clinically occult lymph node
      metastases. Our investigation included 97 patients who underwent supraglottic
      horizontal laryngectomy and elective cervical lymph node dissection. The
      incidence of occult lymph node metastases in the series considered was 27%. Based
      on the preoperative staging of the tumor, 14% of the cases had metastatically
      involved lymph nodes in the T1 tumors, 21% in the T2 tumors, 35% in the T3, and
      75% in the T4. In the statistical analysis, a significant difference was shown to
      exist when T1 + T2 and T3 + T4 (P = 0.04) were compared. In terms of grading,
      occult metastases were found in 16% of the G1 tumors, 27% of the G2, and 42% of
      the G3. The statistical analysis demonstrated a significant difference between G1
      and G3. In brief, the incidence of occult metastases was higher for the less
      differentiated tumors and for the ones with a higher T value; the effects of both
      factors are combined thereby increasing the rate of occult metastases (P = 0.05).

PMID- 11240986
TI  - Supracricoid laryngectomy with CHEP: functional results and outcome.
AB  - OBJECTIVES: To assess whether supracricoid laryngectomy with
      cricohiodoepiglottopexy could successfully reach the cure and preserve the voice
      in glottic laryngeal cancer, we studied 27 patients with T2/T3 squamous cell
      carcinoma of the larynx treated in our institution with cricohiodoepiglottopexy.
      STUDY DESIGN: A retrospective analysis has been carried out between 1995 through
      1997. We classified 11 patients as T2N0M0 and 16 patients as T3N0M0. Nineteen
      patients had bilateral selective lateral neck dissection, 3 patients had
      unilateral lateral neck dissection, and 5 patients had undissected neck. Survival
      was analyzed under the Kaplan-Meyer method. RESULTS: Five patients had
      postoperative complications, 2 were treated with a total laryngectomy. The
      remaining 25 patients kept the normal airway, swallowing, and speech. None of the
      patients in the neck dissection group had neck metastasis. Two patients had
      recurrences, 1 with local recurrence was treated with a total laryngectomy and is
      alive without disease; the other patient had neck recurrence, was treated with
      radical neck dissection plus radiotherapy, and is dead of the disease. One
      patient had a second tumor in oropharynx treated with palliative radiotherapy and
      is dead of the disease. Three years disease-free survival was 75% for T2 and 79%
      for T3. CONCLUSIONS: This technique is useful in the treatment of selected cases
      of T3/T2 glottic cancer regarding the extent of disease. The incidence of
      complications in need of a complete laryngectomy does not compromise the
      functionality of this technique. The survival is comparable to patients who
      submitted to total laryngectomy and near-total laryngectomy, regarding the extent
      of the lesion.

PMID- 11240987
TI  - Extrathyroid spread in papillary carcinoma of the thyroid: clinicopathological
      and prognostic study.
AB  - INTRODUCTION: The extrathyroid spread (ETS) is one of the risk factors that
      influence mortality and recurrence in patients with papillary carcinoma of the
      thyroid (PCT). The aim of this study is to analyze the clinical and histologic
      features and follow-up of a series of patients with ETS undergoing surgery for
      PCT and to identify patients with a greater risk of presenting with ETS. MATERIAL
      AND METHODS: Retrospective study of a series of 200 patients undergoing surgery
      for PCT, of whom 47 (23.5%) presented with ETS. The clinical and histologic
      features and follow-up of the patients with ETS were compared with those without
      ETS using the Pearson chi(2) test. We used a logistics regression model to
      perform a multivariant analysis for ETS. The survival and disease-free interval
      rates were calculated using the Kaplan-Meier method. RESULTS: ETS is most
      associated with patients over 50 years of age, with tumors over 4 cm that are not
      encapsulated, with lymph node metastasis, and with certain PCT histologic
      subtypes after the multivariant analysis. The overall rate of recurrence and
      mortality in patients with ETS was much higher than in patients without ETS.
      CONCLUSIONS: PCT patients with ETS have a greater risk of tumor-related
      recurrence and mortality than patients without ETS. There are patients with
      certain clinical and histologic features who have a greater risk of presenting
      with ETS.

PMID- 11240988
TI  - Small doses of propofol, droperidol, and metoclopramide for the prevention of
      postoperative nausea and vomiting after thyroidectomy.
AB  - OBJECTIVE: To evaluate the efficacy and safety of small doses of propofol,
      droperidol, and metoclopramide for the prevention of postoperative nausea and
      vomiting (PONV) after thyroidectomy. STUDY DESIGN: Prospective, randomized,
      double-blinded study. SETTING: University-affiliated teaching hospital. METHODS:
      In a randomized, double-blinded study, 90 patients (75 females) received propofol
      0.5 mg/kg, droperidol 20 microg/kg, or metoclopramide 0.2 mg/kg intravenously (n
      = 30 in each group) at the end of surgery. A standardized general anesthetic
      technique was used. RESULTS: The incidence of PONV during the first 24 hours
      after anesthesia was recorded in 13%, 47%, and 50% of patients who had received
      propofol, droperidol, and metoclopramide, respectively (P < 0.05; overall Fisher
      exact probability test). No clinically important adverse events were observed in
      any of the groups. CONCLUSION: Small dose (0.5 mg/kg) of propofol is more
      effective than droperidol or metoclopramide for the prevention of PONV after
      thyroidectomy.

PMID- 11240989
TI  - Salivary flow dynamics after parotid surgery: a preliminary report.
AB  - BACKGROUND: Tumors in the parotid gland may affect salivary flow. The effects of
      tumor on glandular function and postoperative changes in both resected gland and
      contralateral gland were not formerly reported. We prospectively evaluated
      salivary flow rates and composition in patients undergoing parotidectomy
      preoperatively and postoperatively. METHOD: Stimulated parotid saliva from 17
      patients undergoing parotidectomy was collected bilaterally preoperatively and
      postoperatively by using a parotid cup. Subjective complaints were recorded.
      Salivary flow rates, sodium, potassium, and amylase levels were evaluated.
      RESULTS: None of the patients complained of "dry mouth" before or after surgery.
      Analysis of the individual results revealed 3 patterns of preoperative and
      postoperative response, compatible with either a preoperative or postoperative
      compensatory mechanism in the contralateral gland. The postoperative decrease in
      flow rate corresponds with the amount of gland removed. Salivary electrolyte
      composition was unchanged. CONCLUSION: This study is the first to demonstrate the
      effects of parotid tumors and their surgery on salivary flow and a compensatory
      response and its different patterns in human parotid glands after their excision.

PMID- 11240990
TI  - Acoustic role of the buttress and posterior incudal ligament in human temporal
      bones.
AB  - OBJECTIVES: In middle ear surgery using intact ear canal wall techniques, the
      buttress, which is the bony bridge at the medial end of the posterior-superior
      bony ear canal, is commonly retained during posterior tympanotomy. In some cases,
      the surgical exposure may be improved by resectioning the buttress, and this
      requires sectioning the posterior incudal ligament. To date, the acoustic effects
      of removing the buttress with sectioning of the attached ligament have not been
      studied. METHOD: Using a laser Doppler vibrometer system, 15 human cadaver
      temporal bones were measured with 80 dB sound pressure level at the tympanic
      membrane over the 0.1 to 10 kHz frequency range. RESULT: The resection of the
      buttress and sectioning the posterior incudal ligament had no effect on stapes
      footplate velocity. CONCLUSION: These results suggest that the posterior incudal
      ligament does not play a significant role in the acoustic function of the
      ossicles.

PMID- 11240992
TI  - Transmastoid decompression as a treatment of Bell palsy.
AB  - OBJECTIVE: We sought to assess the efficacy of transmastoid decompression after
      steroid treatment. STUDY DESIGN: One hundred one adults with Bell palsy having
      denervation exceeding 95% after steroid treatment were divided into 2 groups. In
      58 patients decompression from the labyrinthine segment to the stylomastoid
      foramen was performed, and the remaining 43 patients were only followed up. Using
      the Yanagihara score and House Brackmann grading system, the recovery from the
      palsy was assessed. RESULTS: There was a statistically significant difference in
      the final facial score of the 2 groups. Within 60 days after the onset, the
      chance of better recovery from the palsy was higher in the patients with
      decompression. CONCLUSION: In the era of steroid treatment, we cannot discard the
      transmastoid decompression of the facial nerve in the treatment of severe Bell
      palsy with profound denervation, although further effort is needed to obtain
      definitive evidence to show the benefit of the operation.

PMID- 11240991
TI  - Effect of teflon piston diameter on hearing result after stapedotomy.
AB  - This study compares hearing results after stapedotomy by 0.6 mm and 0.8 mm teflon
      pistons. Retrospective analysis studied 100 patients randomly selected who
      underwent stapedotomy for otosclerosis with insertion of 0.8 mm teflon piston
      prosthesis and 100 patients with 0.6 mm teflon piston prosthesis. Air-conduction
      hearing level in both groups were measured before and after the procedure and the
      gain of the air conduction between the 2 groups at different frequencies were
      compared statistically. The group with the 0.8 mm prosthesis had better results
      that were statistically significant and more pronounced at lower frequencies.

PMID- 11240993
TI  - Modified retrolabyrinthine approach with partial labyrinthectomy: anatomic study.
AB  - This study was undertaken to evaluate the feasability of the modified
      retrolabyrinthine approach (traditional retrolabyrinthine approach plus resection
      of the posterior semicircular canal) to expose the entire fundus of the internal
      auditory canal (IAC). This approach is advocated by its proponents to manage
      acoustic neuromas reaching the lateral IAC and with the preservation of hearing
      as the goal. Little anatomic data directly estimate the limitations of this
      exposure. Measurements were recorded from 25 cadaver temporal bones dissected
      with this modified approach. The distances were taken between the porus
      acousticus (inferior and superior portions), the dome of the jugular bulb, the
      midportion of the sigmoid sinus, and the fundus of the IAC (inferior and superior
      portions). All of the measurements were then compared with those of the
      translabyrithine approach. The current study shows that despite the sacrifice of
      the posterior semicircular canal, the superior lateral fundus cannot be
      completely visualized. There is a distance (on average 1.1 mm) that
      differentiates the superior area of the IAC accessible with translabyrithine and
      modified retrosigmoid techniques. This value is smaller than that observed in the
      classic retrosigmoid approach indicating that the modified technique affords a
      more adequate, even if not ideal, exposure to minimize the risk of recurrence.
      The modified retrolabyrinthine approach provided an optimal exposure of the
      inferior half of the IAC. A superior blind area, smaller than that of the
      traditional retrolabyrinthine technique, cannot be completely approached via this
      route. We believe that this approach can be considered as an alternative
      technique in selected cases especially for tumors involving the inferior
      vestibular nerve.

PMID- 11240994
TI  - Facial translocation approach to the skull base: the viability of translocated
      facial bone graft.
AB  - OBJECTIVES: A retrospective review of 56 patients who were operated through a
      facial translocation approach was carried out to assess the viability of the
      translocated facial bone segment. METHODS: Eleven patients had preoperative
      radiotherapy, and 26 had postoperative radiotherapy. In 14 patients the
      translocated bone segment was kept attached to the anterior cheek, and in 42
      patients the bone segment was detached and then implanted. A vascularized flap
      was used to obliterate the defect in the paranasal sinuses in 15 patients.
      RESULTS: Twelve (21.4%) patients had devitalized bone segment and required
      sequestrectomy. The incidence of devitalized bone segment was higher in the
      patients who received postoperative radiotherapy (P = 0.04) and lower in the
      patients in whom the defect in the paranasal sinuses was reconstructed with a
      vascularized flap (P = 0.006). CONCLUSIONS: The translocated facial bone segment
      should be kept attached to the cheek soft tissue when possible, or the defect in
      the paranasal sinuses should be reconstructed with a vascularized flap.

PMID- 11240995
TI  - A tongue suspension suture for obstructive sleep apnea and snorers.
AB  - OBJECTIVE: A tongue suture is postulated to prevent tongue base collapse in
      obstructive sleep apnea (OSA) and snoring. This procedure uses a permanent tongue
      base suture to support the pharynx and lessen collapse. This study evaluates 2
      month results in 28 OSA and snoring patients. STUDY DESIGN AND SETTINGS: Forty
      three patients have been enrolled in a multi-institutional prospective open
      enrollment study using the "Repose" bone screw system. Subjects were evaluated
      using polysomnography measures of general health (SF-36), snoring, and sleep
      (Epworth Sleepiness Scale and Functional Outcomes of Sleep) performed before and
      again 2 months after treatment. RESULTS: In 14 OSA patients (Apnea + Hypopnea
      (AHI) > 15) and 14 snorers (AHI < 15), no change was noted in sleep architecture
      or lowest oxygen saturation. AHI decreased in OSA (35.4 +/- 13.7 to 24.5 +/-
      14.5, P < 0.00), but not in snorers. AHI decreased in the lateral (16.5 +/- 16.5
      to 3.8 +/- 6.4, P < 0.01) but not the supine position. Epworth Sleepiness Scale,
      Functional Outcomes of Sleep, and snoring scales improved. Snoring decreased but
      remained bothersome to the bed partner. CONCLUSIONS: A tongue suspension suture
      partially reduces the respiratory severity of OSA. Small changes are noted in
      symptoms of sleepiness, snoring, and functional outcomes. Demonstration of
      efficacy of the technique and device will require further controlled trials.

PMID- 11240996
TI  - Frontal sinus obliteration with the pericranial flap.
AB  - BACKGROUND: Frontal sinus obliteration is often accomplished by autologous grafts
      such as fat, muscle, or bone. These avascular grafts carry an increased risk of
      resorption and infection as well as donor site morbidity. Vascular regional flaps
      may be used to obliterate small sinuses with less morbidity. OBJECTIVES: To
      review our experience with the use of the pericranial flap for obliteration of
      the frontal sinus. METHODS: The records of 10 patients who underwent obliteration
      of the frontal sinus with the pericranial flap were reviewed. Demographics,
      indications for frontal sinus obliteration, immediate and late complications, and
      long-term outcome were recorded. These results were compared with those in the
      current literature. RESULTS: Ten sinuses were obliterated with the pericranial
      flap. Indications included frontal sinus mucocele, mucopyocele, frontal sinus
      osteomyelitis, and frontal sinus fracture. The median follow-up was 3 years.
      There was 1 short-term complication of persistent headache for 1 month, and there
      was asymptomatic recurrence of a neofrontal sinus in 1 case. CONCLUSIONS: The
      pericranial flap is a vascularized local flap that is easily harvested. The use
      of the pericranial flap avoids donor site morbidity associated with free fat or
      cancellous bone grafts. The pericranial flap arms the head and neck surgeon with
      an effective alternative to other methods of frontal sinus obliteration.

PMID- 11240997
TI  - Injury to the lacrimal apparatus after endoscopic sinus surgery: surgical
      implications from active transport dacryocystography.
AB  - In order to evaluate the lacrimal drainage system injury after functional
      endoscopic sinus surgery, surgical records and postoperative active transport
      dacryocystography imaging of 31 patients were analyzed. Presence of the lacrimal
      bone dehiscence and no passage of the contrast material into the inferior meatus
      were noted as the signs of injury to the lacrimal canal on active transport
      dacryocystography. Bony dehiscence was detected in 53.2% of the operated sides
      but 20% of the nonoperated sides. No passage of the contrast material into the
      inferior meatus was observed in 14.9% of the operated sides. There were no cases
      of epiphora postoperatively. The lacrimal drainage system injury was more
      frequently observed on the left sides operated. We conclude that lacrimal
      drainage system injury might occur in various extents during functional
      endoscopic sinus surgery. However, it does not necessarily result in
      postoperative epiphora. Performing the middle meatal antrostomy in
      posteroinferior direction, and uncinectomy with backbiting forceps or a shaver
      might help in reducing the lacrimal injury. Active transport dacryocystography
      can be adopted as an alternative diagnostic tool in detection of the lacrimal
      injury.

PMID- 11240998
TI  - Hypertonic saline decreases ciliary movement in human nasal epithelium in vitro.
AB  - Various saline solution formulae are frequently used in patients with
      rhinosinusitis. Osmolarity affects ciliary beat frequency (CBF); however, little
      is known about the effects of saline solutions on ciliary activity of nasal
      epithelial cells. The aim of this study was to assess whether CBF of normal
      turbinate mucosa is affected by hypertonic, isotonic, or hypotonic saline
      solution in vitro and whether histologic changes are associated with the
      alteration of ciliary movement. We assessed variations of CBF after exposure to
      0.06%, 0.12%, 0.9%, 3.0%, or 7.0% saline solutions and histologic changes were
      examined by transmission electron microscopy. Isotonic and hypotonic solutions
      produced no ciliary slowing; however, ciliostasis was observed within a few
      minutes in 3.0% or 7.0% solution. The histologic changes demonstrated that the
      ciliary slowing might be attributed to epithelial damage by fluid transport
      toward the surrounding medium. In conclusion, hypertonic saline solutions
      decrease CBF and disrupt nasal epithelial cells in vitro.

PMID- 11240999
TI  - Analysis of vocal fold vibration by x-ray stroboscopy with multiple markers.
AB  - OBJECTIVE: To derive a more precise description of vocal fold vibration,
      experimental phonation of excised canine larynxes was studied. STUDY DESIGN AND
      SETTING: Multiple X-ray-positive markers were inserted, and their vibratory
      movement was observed with x-ray stroboscopy with change of pitch and intensity.
      A histologic study was also carried out. RESULT: Regular waves were observed just
      above the lowest point of the lamina propria of the mucous membrane, which
      shifted upward at high pitch, but downward in high intensity. CONCLUSIONS: The
      starting point of the mucosal wave was confirmed on the lower surface of the
      vocal fold, histologically just above the lowest point of the lamina propria of
      the mucous membrane and shifted upward at high pitch, but downward in high
      intensity. SIGNIFICANCE: This is the first study investigating the starting point
      of mucosal wave in vocal fold vibration in a frontal plane using x-ray
      stroboscopy, providing the evidence for the body-cover theory.

PMID- 11241000
TI  - Normal standard curve for acoustic pharyngometry.
AB  - Pharyngeal size, compliance, and the dynamic behavior of the upper airway are
      important factors in the production of obstructive sleep apnea. Assessment of the
      upper airway for possible site(s) of obstruction is one of the keys to a
      successful management of the condition. Acoustic pharyngometry has the potential
      for localizing such sites, however, standardizing the operating technique and
      producing a standard normal curve is a prerequisite before exploring the
      potential of this equipment. A total number of 350 normal volunteers (271 males
      and 79 females) were examined by acoustic pharyngometry and a coefficient of
      variance of 5% to 7% was obtained from each of them. Mean and standard deviation
      of pharyngeal area at each point of X-axis (distance) was obtained and analyzed
      statistically to produce a general standard curve. Using special techniques
      during examination, the oropharyngeal junction and glottis were located, and thus
      a mapped acoustic pharyngogram was produced. Mean pharyngeal area was 3.194 cm(2)
      in males (SD 0.311) and 2.814 cm(2) in females (SD 0.331). Mean glottic area was
      1.06 cm(2) in males (SD 0.119) and 0.936 cm(2) in females (SD 0.108). A minimal
      pharyngeal area is probably needed as a "golden standard" to evaluate patients
      with obstructive sleep apnea.

PMID- 11241001
TI  - Oncologic rationale for bilateral tonsillectomy in head and neck squamous cell
      carcinoma of unknown primary source.
AB  - OBJECTIVE: To demonstrate an oncologic basis for the recommendation to perform
      bilateral tonsillectomy as a routine measure in the search for a primary mucosal
      lesion in patients presenting with cervical nodal metastasis of squamous cell
      carcinoma (SCC). STUDY DESIGN: A case series of individuals selected from a 3
      year period is reported. SETTING: Academic medical center. RESULTS: Each
      individual presented with metastatic squamous cell carcinoma in a cervical lymph
      node from an unknown primary source. In each case, the primary source was
      identified in a tonsillectomy specimen, either located contralateral to the node,
      or in both tonsils. CONCLUSIONS: The rate of contralateral spread of metastatic
      cancer from occult tonsil lesions appears to approach 10%. For this reason,
      bilateral tonsillectomy is recommended as a routine step in the search for the
      occult primary in patients presenting with cervical metastasis of SCC and
      palatine tonsils intact.

PMID- 11241002
TI  - Nasopharyngeal Burkitt's lymphoma causing acute airway obstruction.

PMID- 11241003
TI  - Endonasal endoscopic surgery for nasopharyngeal angiofibroma.

PMID- 11241004
TI  - Localized Paget's disease with mucocele in the sphenoid sinus.

PMID- 11241005
TI  - Ectopic thyroid tissue manifesting as a unique cause of an oropharyngeal mass.

PMID- 11241006
TI  - Malignant myoepithelioma arising within the masticator space ectopically.

PMID- 11241007
TI  - Adult onset spontaneous CSF otorrhea with oval window fistula and recurrent
      meningitis: MRI findings.

PMID- 11241008
TI  - Blastomycosis of the petrous apex.

PMID- 11241009
TI  - Otogenic meningitis caused by the pneumococci that had acquired resistance to
      cephalosporins.

PMID- 11241010
TI  - Oropharyngeal Kaposi's sarcoma.

PMID- 11241011
TI  - Congenital macrostomia.

PMID- 11241013
TI  - Calculation of mitral regurgitant orifice area with use of a simplified proximal
      convergence method: initial clinical application.
AB  - To validate a previously proposed simplified proximal flow convergence method for
      calculating mitral regurgitant orifice area (ROA), a prospective study was
      conducted in ambulatory patients and in patients undergoing open heart surgery.
      Assuming a pressure difference between the left ventricle and left atrium of
      approximately 100 mm Hg (jet velocity [v(p)] 500 cm/s) and setting the color
      aliasing velocity (v(a)) to 40 cm/s, we simplified the conventional proximal
      convergence method formula (ROA = 2pi(r2)v(a)/v(p)) to r2/2, where r is the
      radius of the proximal convergence isovelocity hemisphere. For 57 ambulatory
      patients with a wide range of mitral regurgitant severity (1 to 4+), ROA was
      calculated by the conventional (x) and simplified (y) methods, demonstrating
      excellent accuracy (r = 0.92; P <.001; DeltaROA [y - x] = 0.004 +/- 0.08 cm2).
      For 24 intraoperative patients, ROA calculated by the simplified formula (y)
      correlated well with the pulsed Doppler-thermodilution method (x) (r = 0.84; P
      <.01; DeltaROA [y - x] = -0.002 +/- 0.08cm2). This simplified proximal
      convergence formula yields an accurate assessment of ROA for a wide range of
      regurgitant severity, while the time required for this measurement is shortened
      by half (1.5 +/- 0.5 minutes versus 3.2 +/- 0.7 minutes). This may increase the
      frequency of calculating ROA in the clinical laboratory.

PMID- 11241012
TI  - Measurement of left ventricular volumes by 3-dimensional echocardiography with
      tissue harmonic imaging: a comparison with magnetic resonance imaging.
AB  - We hypothesized that tissue harmonic imaging (THI) in comparison with fundamental
      imaging (FI) would improve endocardial border detection, and therefore in
      combination with 3-dimensional echocardiography (3D echo), it would be a precise
      method for left ventricular (LV) volume measurement. Ten healthy subjects and 18
      consecutive patients with dilated hearts underwent estimation of LV volumes by
      magnetic resonance imaging (MRI) and transthoracic 3D echo with THI and FI. In
      patients, the agreement between MRI and 3D echo was closer with THI in comparison
      with FI for assessment of LV volumes. Thus the mean +/- 2 SD of differences
      between MRI and 3D echo with THI versus FI, respectively, was -6.4 +/- 40.0 mL
      versus -17.4 +/- 57.6 mL (P <.01) for the end-diastolic volume (EDV), and 0.0 +/-
      26.6 mL versus -8.1 +/- 35.6 mL (P <.01) for the end-systolic volume (ESV). In
      patients, THI in comparison with FI approximately halved observer variation on
      EDV and ESV. In healthy subjects, only ESV showed significantly reduced observer
      variation by THI. In conclusion, because THI demonstrated a clinically relevant
      reduction in observer variation and a closer agreement to the MRI technique in
      patients with dilated hearts, it should replace FI in LV volume measurements.

PMID- 11241014
TI  - Atrial and ventricular electromechanical function in 1-ventricle hearts:
      influence of atrial flutter and Fontan procedure.
AB  - OBJECTIVE: Echocardiography was used to study electromechanical atrial and
      ventricular function in adult patients with a 1-ventricle heart who were in sinus
      rhythm to better understand the recurrence of atrial flutter in these conditions.
      Patients who had recent atrial flutter, with and without the Fontan procedure,
      were compared with those who had no arrhythmia. METHODS: This was a prospective
      study that used M-mode and 2-dimensional Doppler echocardiography and
      electrocardiography. Conventional measurements were used to evaluate ventricular
      long-axis function. Basic data were drawn from case notes. The setting was a
      designated quaternary service for grown-up congenital heart patients (GUCH) in a
      tertiary referral center for cardiology and cardiac surgery. From January 1997 to
      February 1998, 26 consecutive adult patients (aged >16 years) with a heart with
      one functioning ventricle and a history of atrial flutter were studied: group 1,
      with non-Fontan palliative surgery or no surgery (10 patients), and group 2, with
      Fontan-type repair (16 patients). Also studied were 20 patients with a 1
      ventricle heart but no history of atrial flutter. These 20 patients were divided
      into 2 groups: control 1, which comprised 14 patients with previous shunts or no
      surgery, and control 2, which consisted of 6 patients with Fontan repair.
      RESULTS: P-wave duration on the electrocardiogram was similar in the 4 patient
      groups, but the amplitude was reduced in group 2 and control 2 (patients with
      Fontan surgery) (P <.016). Bifid P wave was seen in 5 (50%) of 10 patients in
      group 1 and in 6 (43%) of 14 patients in control 1, but it was not seen in
      patients with Fontan (P <.01). Ventricular systolic and diastolic dimensions and
      fractional shortening were not different between patients and controls. Right
      atrial transverse dimensions were greater in group 2 patients compared with those
      in controls. Significant atrioventricular valve regurgitation was seen in 9 of 10
      group 1 patients but in none of the others. Right-sided total long-axis excursion
      and atrial A-wave amplitude were depressed in group 2 patients compared with the
      values in the others. The onset of right atrial shortening was delayed by 50 ms
      in group 2 compared with control 2, whereas the left atrial shortening was
      delayed by 30 ms in group 1 compared with control 1. This particular disturbance
      remained 6 months after cardioversion. CONCLUSION: In 1-ventricle hearts,
      significant atrioventricular valve regurgitation is commonly associated with
      atrial flutter in patients who did not undergo the Fontan procedure, and with
      electromechanical disturbances in those who did. Recognition of disturbances in
      ventricular long-axis function may thus assist in the identification of patients
      with a 1-ventricle heart who are prone to atrial flutter.

PMID- 11241016
TI  - Potential clinical efficacy and cost benefit of a transesophageal
      echocardiography-guided low-molecular-weight heparin (enoxaparin) approach to
      antithrombotic therapy in patients undergoing immediate cardioversion from atrial
      fibrillation.
AB  - An alternative clinical management strategy and cost analysis model is presented
      for patients with atrial fibrillation of >2 days' duration who may benefit from
      immediate cardioversion with self-administered low-molecular-weight heparin
      (enoxaparin) as a bridge antithrombotic therapy to warfarin, after a negative
      transesophageal echo-cardiography (TEE) screening for thrombus. Assuming no
      difference in stroke or bleeding rates, our cost minimization model shows that
      the TEE-guided enoxaparin treatment costs are $1353 lower per patient than an
      intravenous unfractionated heparin approach. Sensitivity analyses for stroke and
      bleeding reveal that the treatment-cost economic dominance of the TEE-guided
      enoxaparin approach may be enhanced by an expected improvement in clinical
      outcome.

PMID- 11241015
TI  - Does acute-phase beta blockade reduce left atrial appendage function in patients
      with chronic nonvalvular atrial fibrillation?
AB  - To investigate whether acute-phase beta-blocker therapy has a harmful effect on
      left atrial appendage (LAA) function in patients with chronic nonvalvular atrial
      fibrillation by transesophageal echocardiography (TEE), we evaluated 21 patients
      with normal left ventricular systolic function and a poorly controlled
      ventricular rate, despite the use of digoxin. Baseline parameters that were
      obtained included heart rate, blood pressure, LAA emptying velocities, and left
      atrial spontaneous echo contrast intensity. Then, each patient was given a bolus
      dose of 5 mg metoprolol. Ten minutes later, a second set of assessments was
      performed. After the first TEE studies, each patient began treatment with
      metoprolol (50 mg orally twice daily for 1 week). A second TEE study was
      performed after 1 week of continuous oral metoprolol therapy at maintenance dose,
      and values were again determined. The average resting apical heart rate was 91 +/
      7 bpm. As expected, beta-blocker therapy showed a marked decrease in heart rate
      at 10 minutes (79 +/- 6 bpm, P <.001) and at 1 week (71 +/- 4 bpm, P <.001). Beta
      blocker therapy caused a significant reduction in systolic and diastolic blood
      pressures (144 +/- 16 / 93 +/- 6 mm Hg at baseline, 137 +/- 16 / 87 +/- 9 mm Hg
      at 10 minutes, and 135 +/- 12 / 86 +/- 8 mm Hg at 1 week, P <.001). With the beta
      blocker therapy, the baseline transesophageal Doppler parameter of LAA emptying
      velocities (at baseline 24 +/- 7 cm/s) fell significantly at 10 minutes (19 +/- 7
      cm/s, P <.001) and at 1 week (17 +/- 6 cm/s, P <.001) after initiation of beta
      blocker therapy. After a bolus of metoprolol, spontaneous echo contrast intensity
      did not change in any patients, but 1 week later, it increased in 1 patient. In 2
      patients who had not been found to have an LAA thrombus at baseline TEE study,
      the second TEE examination demonstrated new thrombi in the LAA. In conclusion,
      our findings suggest that in patients with chronic nonvalvular atrial
      fibrillation who have normal left ventricular systolic function and a poorly
      controlled ventricular rate despite the use of digoxin, acute-phase beta blockade
      may have a harmful effect on LAA function.

PMID- 11241017
TI  - The left ventricular stress-velocity relation in transgenic mice expressing a
      dominant negative CREB transgene in the heart.
AB  - OBJECTIVE: CREB(A133) transgenic mice that express a dominant negative CREB
      transcription factor in cardiomyocytes develop a dilated cardiomyopathy that is
      anatomically, physiologically, and clinically similar to human idiopathic dilated
      cardiomyopathy. The goals of this study were to quantitate left ventricular (LV)
      contractility and measure cardiac reserve in CREB(A133) mice by using the
      relation of end-systolic wall stress to the velocity of fiber shortening.
      METHODS: A total of 37 adult CD-1 mice (including both nontransgenic and
      CREB(A133) transgenic mice) were studied with simultaneously acquired high
      fidelity instantaneous aortic pressures and 2-dimensionally targeted M-mode
      echocardiograms. RESULTS: CREB(A133) mice displayed significantly lower values of
      LV fiber shortening velocities over a wide range of afterloads, and they
      displayed smaller dobutamine-induced shifts from baseline contractility
      relations. Counterbalancing effects of differences in LV geometry and aortic
      pressures resulted in comparable levels of LV wall stress during ejection in both
      groups. CONCLUSION: These results demonstrate directly that CREB(A133) mice
      display reduced LV contractility at baseline and decreased cardiac reserve.

PMID- 11241018
TI  - Unusual form of cardiac rupture: sealed subacute left ventricular free wall
      rupture, evolving to intramyocardial dissecting hematoma and to pseudoaneurysm
      formation--a case report and review of the literature.
AB  - This report describes an unusual course of rupture of the left ventricular free
      wall, complicating acute myocardial infarction. Spontaneous sealing of the
      rupture site enabled close echocardiographic follow-up, during which we monitored
      the development of intramyocardial dissecting hematoma and, finally, development
      of a full tear in the left ventricular free wall, leading to the formation of a
      pseudoaneurysm. The pathophysiology, management, and diagnostic criteria of these
      processes are being revised.

PMID- 11241020
TI  - Abnormal implantation of permanent pacemaker lead in the left ventricle via a
      patent foramen ovale: clinical and echocardiographic recognition of a rare
      complication.
AB  - An 84-year-old man with a history of permanent pacemaker placement had a
      preoperative cardiac evaluation for prostate cancer surgery. The patient was
      asymptomatic, and the results of a physical examination were consistent with a
      right bundle branch block, which was confirmed by electro-cardiogram as his paced
      rhythm. A chest radiograph raised the possibility of an abnormal lead location,
      and transthoracic echocardiography confirmed the mechanism of an abnormal
      placement of the pacemaker lead. Left ventricular location of pacemaker is rare,
      and awareness of its clinical and imaging findings, complications, and management
      options is important for clinicians involved in the care of patients with
      pacemakers.

PMID- 11241019
TI  - Left ventricular pseudoaneurysm as a complication of electrophysiologic study.
AB  - We have described a patient who developed a small submitral pseudoaneurysm of the
      left ventricle during electrophysiologic mapping aimed at ablating a concealed
      accessory pathway. The patient was asymptomatic, and the lesion was detected on a
      routine postprocedure echocardiographic study. Spontaneous healing occurred, and
      the lesion was no longer seen on a repeated echocardiographic examination
      performed a month later.

PMID- 11241021
TI  - Benign lipid envelope of the heart simulating a pericardial hematoma.
AB  - The hallmark of diagnosing a pericardial effusion by echocardiography is the
      presence of relatively sonolucent space outside of the cardiac structures. The
      location, size, mobility, and consistency of the pericardial space determined by
      echocardiography are considered to be reliable markers for defining pericardial
      processes. In certain clinical scenarios, however, it may be difficult to
      differentiate fluid from other pericardial processes, notably subepicardial
      adipose tissue. This case of a 76-year-old woman, who presented with possible
      cardiac tamponade after permanent pacemaker implantation, demonstrates some of
      the potential pitfalls in the diagnosis of pericardial space abnormalities.

PMID- 11241022
TI  - An unusual case of vegetative aortitis diagnosed by transesophageal
      echocardiography.
AB  - We report a case of Staphylococcus aureus aortitis in a 42-year-old man who had a
      fever, an embolus to the left upper arm, and positive blood cultures.
      Transesophageal echocardiography re-vealed a 3 x 1-centimeter polypoid mass
      attached to the intima of the medial wall of the aorta, just distal to the origin
      of the left subclavian artery. The clinical presentation and the transesophageal
      echocardiography findings led to the diagnosis of vegetative aortitis. Antibiotic
      therapy was begun, and 5 days later the mass was surgically excised to prevent
      the possible formation of an infective aortic aneurysm and embolization to the
      vital organs.

PMID- 11241023
TI  - Role of dobutamine echocardiography in detection of myocardial viability for
      predicting outcome after revascularization in ischemic cardiomyopathy.
AB  - Coronary artery disease is the most common cause of heart failure in the Western
      world. Compared with medical therapy, surgical revascularization has been shown
      to improve survival rates in nonrandomized trials in patients with ischemic
      cardiomyopathy. However, perioperative mortality is high in this group of
      patients who do not demonstrate significant viable myocardium. Echocardiography
      during dobutamine infusion has been shown to reliably detect viable myocardium.
      Several studies have demonstrated its ability to provide high predictive value
      for recovery of both regional and global left ventricular function after
      revascularization. Indeed, nonrandomized studies also have indicated its value in
      predicting which patients with severe ischemic cardiomyopathy are likely to
      survive after revascularization. Dobutamine stress echocardiography has emerged
      as a safe and valuable technique for the assessment of myocardial viability and
      for the selection of patients for revascularization.

PMID- 11241024
TI  - Natural history of chronic hepatitis C: identifying a window of opportunity for
      intervention.

PMID- 11241025
TI  - Adenovirus-mediated transfer of the atrial natriuretic peptide gene in rat
      pulmonary vascular smooth muscle cells leads to apoptosis.
AB  - Atrial natriuretic peptide (ANP) exhibits relaxant and growth-inhibiting effects
      on vascular smooth muscle cells (VSMCs). To obtain ANP gene expression in VSMCs,
      we built a recombinant adenovirus containing the ANP cDNA controlled by the
      adenovirus major late promotor (AdMLP-ANP). After pulmonary VSMC treatment with
      AdMLP-ANP at a multiplicity of infection ranging from 5 to 100 TCID(50)/cell,
      immunoreactive ANP was detectable in the cell culture medium at a level that
      reached 101 +/- 27 pmol/well after 2 days. The newly expressed ANP was
      biologically active, as evidenced by its ability to induce cyclic guanosine
      monophosphate accumulation in target cells and to mimic the effect of exogenous
      ANP (10(-8) to 10(-7) mol/L). Cell growth and survival of AdMLP-ANP-infected
      cells were decreased and were associated with the promotion of VSMC apoptosis.
      These effects, which occurred at a multiplicity of infection of 10 to 100
      TCID(50)/cell, were observed neither in cells infected with the control
      adenoviral constructs (AdMLP-betaGAL and AdMLP-gD) nor in cells treated with
      exogenous ANP (10(-7) to 10(-6) mol/L). These results showing VSMC apoptosis in
      response to ANP gene expression may have important implications for the
      prevention of vascular remodeling by gene therapy.

PMID- 11241026
TI  - Distribution of iodine 125-labeled alpha1-microglobulin in rats after intravenous
      injection.
AB  - The 28-kd plasma protein alpha(1)-microglobulin is found in the blood of mammals
      and fish in a free, monomeric form and as high-molecular-weight complexes with
      molecular masses above 200 kd. In this study, iodine 125-labeled free and high
      molecular weight rat alpha(1)-microglobulin (a mixture of alpha(1)
      microglobulin/alpha(1)-inhibitor-3 and alpha(1)-microglobulin/fibronectin
      complexes) were injected intravenously into rats. The distribution of the
      proteins was measured by using scintillation camera imaging. Both forms of (125)I
      labeled alpha(1)-microglobulin were rapidly cleared from the blood, with a half
      life of 2 and 16 minutes for the initial and late phase, respectively, for free
      alpha(1)-microglobulin; and a half-life of 3 and 130 minutes for the initial and
      late phase, respectively, for the complexes. After 45 minutes, 6%, 16%, 27%, 13%,
      and 34% of the free (125)I-labeled alpha(1)-microglobulin and 18%, 21%, 6%, 10%,
      and 42% of the (125)I-labeled alpha(1)-microglobulin complexes were found in the
      blood, gastrointestinal tract, kidneys, liver, and the remainder of the body,
      respectively. The local distribution of injected (125)I-labeled alpha(1)
      microglobulin in intestines and kidneys was investigated by microscopy and
      autoradiography. In the intestine, both forms were distributed in the basal
      layers, villi, and luminal contents. The results also suggested intracellular
      labeling of epithelial cells. Well-defined local regions containing higher
      concentrations of injected protein could be seen in the intestine. In the
      kidneys, both forms were found mostly in the cortex. Free (125)I-labeled alpha(1)
      microglobulin was found predominantly in epithelial cells of a subset of the
      tubules, whereas the (125)I-labeled complexes were more evenly distributed.
      Intracellular labeling was indicated for both alpha(1)-microglobulin forms. The
      results thus indicate a rapid transport of (125)I-labeled alpha(1)-microglobulin
      from the blood to most tissues.

PMID- 11241027
TI  - Effect of erythromycin on matrix metalloproteinase-9 and cell migration.
AB  - Erythromycin (EM) has an anti-inflammatory effect that may account for its
      clinical benefit in the treatment of chronic inflammatory diseases such as
      diffuse panbronchiolitis. To investigate the mechanism of this anti-inflammatory
      effect, we studied the relationship between the concentration of EM and matrix
      metalloproteinase-9 (MMP-9) activity, which is important in cell migration. We
      showed that EM suppressed the gelatinolytic activity of U937 cell-derived MMP-9
      by using gelatin zymography, showed that expressions of MMP-9 protein and MMP-9
      mRNA were down-regulated by EM in a dose-dependent manner, and showed that U937
      migration was also suppressed by EM. We also demonstrated that EM treatment
      suppressed the gelatinolytic activity of MMP-9 in spleen macrophages. These
      findings suggest that the suppressive effect of EM on MMP-9 activity is one of
      the anti-inflammatory mechanisms that inhibit the migration of inflammatory cells
      into the inflammatory site.

PMID- 11241028
TI  - Differentiation of populations with different physiologic profiles by plasma
      Fourier-transform infrared spectra classification.
AB  - The pathologic condition of a patient presenting a metabolic disease can change
      rapidly, and a variety of pathologic conditions are possible. Plasma Fourier
      transform infrared (FT-IR) spectra were used to differentiate patients with type
      1 diabetes, healthy subjects, and endurance-trained rowers. Analytic and
      classification methods that use the same plasma FT-IR spectra are described.
      Complete spectra (4000 to 500 cm(-1)) classifications led to a differentiation
      between most patients with type 1 diabetes and other subjects but not between
      control and trained subjects. Classification of defined absorption regions of
      spectra allowed different metabolic distinctions between populations. These were
      performed on the amide I and II absorption regions of proteins (1720 to 1480 cm(
      1)); on the nu=CH, nu(as)CH(2), and nu(as)CH(3) absorption regions of lipids
      (3020 to 2880 cm(-1)); and on the nuC-O absorption region of saccharides (1300 to
      900 cm(-1)). A classification that uses a combination of four absorption regions
      nu=CH (3020 to 3000 cm(-1)), nu(as)CH(3) (3000 to 2950 cm(-1)), nuC-O (amide I:
      1720 to 1600 cm(-1)), and nuC-O (carbonyle: 1300 to 900 cm(-1))-led to the
      formation of three exclusive clusters that comprised the defined populations. FT
      IR spectroscopy is an exciting technique that allows a versatile approach to
      biologic samples from which analytic and statistical methods might be used for
      metabolic profile characterization and evaluation.

PMID- 11241029
TI  - Treatment of Wilson's disease with zinc XVI: treatment during the pediatric
      years.
AB  - The objectives were to evaluate appropriate doses of zinc acetate and its
      efficacy for the maintenance management of Wilson's disease in pediatric cases.
      Pediatric patients of 1 to 5 years of age were given 25 mg of zinc twice daily;
      patients of 6 to 15 years of age, if under 125 pounds body weight, were given 25
      mg of zinc three times daily; and patients 16 years of age or older were given 50
      mg of zinc three times daily. Patients were followed for efficacy (or over
      treatment) until their 19th birthday by measuring levels of urine and plasma
      copper, urine and plasma zinc and through liver function tests and quantitative
      speech and neurologic scores. Patients were followed for toxicity by measures of
      blood counts, blood biochemistries, urinalysis, and clinical follow-up. Thirty
      four patients, ranging in ages from 3.2 to 17.7 years of age, were included in
      the study. All doses met efficacy objectives of copper control, zinc levels,
      neurologic improvement, and maintenance of liver function except for episodes of
      poor compliance. No instance of over-treatment was encountered. Four patients
      exhibited mild and transient gastric disturbance from the zinc. Zinc therapy in
      pediatric patients appears to have a mildly adverse effect on the high-density
      lipoprotein/total cholesterol ratio, contrary to results of an earlier large
      study of primarily adults. In conclusion, zinc is effective and safe for the
      maintenance management of pediatric cases of Wilson's disease. Our data are
      strongest in children above 10 years of age. More work needs to be done in very
      young children, and the cholesterol observations need to be studied further.

PMID- 11241030
TI  - A fast and simple screening test to search for specific inhibitors of the plasma
      membrane calcium pump.
AB  - No specific inhibitors of the plasma membrane Ca(2+) pump have been found to
      date, limiting research on the particular contribution of this pump to the Ca(2+)
      homeostasis of animal cells. The search for Ca(2+) pump inhibitors may have been
      hampered by the lack of an efficient screening method to measure pump activity
      that would provide an alternative to the lengthy and costly adenosine
      triphosphatase or Ca(2+)-flux measurements. We propose here a novel screening
      method in which Ca(2+) pump inhibition is translated into easily measurable cell
      dehydration. Intact human red cells, suspended in Ca(2+)-containing, low-K(+)
      buffers were exposed to sequential additions of (1) ionophore A23187 (t = 0) to
      load the cells with Ca(2+); (2) CoCl(2) (t = 1 minute) to block ionophore
      mediated Ca(2+) transport and to allow complete extrusion of the Ca(2+) load by
      the pump in less than 5 minutes; and (3) NaSCN (t = 6 minutes) to accelerate cell
      dehydration via Ca(2+)-sensitive K(+) channels when the Ca(2+) load is retained
      as a result of Ca(2+) pump inhibition. Samples were taken at 10 to 25 minutes
      after ionophore addition and delivered into hypotonic media containing about 45
      mmol/L NaCl. Non-dehydrated cells-with normal, uninhibited pumps-instantly
      underwent lysis, whereas dehydrated cells-with inhibited pumps-resisted lysis,
      resulting in translucent or opaque samples, respectively, which were quantifiable
      by light-absorption measurements. Vanadate was used as a test substance to assess
      the effect of putative pump inhibitors. This method offers a cost-efficient and
      easily automated alternative for testing large numbers of natural or synthetic
      agents.

PMID- 11241031
TI  - Cigarette smoke inhibits osteogenic differentiation and proliferation of human
      osteoprogenitor cells in monolayer and three-dimensional collagen gel culture.
AB  - Cigarette smoke is a risk factor not only for emphysema but also for other
      disorders characterized by deficient tissue repair, including osteoporosis. We
      hypothesized, therefore, that smoke might directly impair bone cell repair
      processes. To evaluate this, bone marrow osteoprogenitor cells were isolated from
      normal subjects and cultured in monolayer and in three-dimensional type I
      collagen gel culture. Human osteoprogenitor cells could be induced to
      differentiate toward osteoblast-like cells in both culture conditions by
      osteogenic supplements. Under both culture conditions, cigarette smoke extract
      (CSE) inhibited the proliferation of osteoprogenitor cells in a concentration
      dependent manner. CSE also inhibited differentiation of osteoprogenitor cells
      toward osteoblast-like cells as assayed by alkaline phosphatase activity and
      calcium incorporation into cell layer. Cells in monolayer culture were more
      sensitive to the effect of smoke than cells in three-dimensional gel culture.
      Similar results were obtained with osteoblast-like cells derived from
      osteosarcomas. This study, therefore, demonstrates that cigarette smoke may
      affect bone progenitor cells directly and in this manner may contribute to the
      development of osteoporosis.

PMID- 11241032
TI  - Influenza vaccine in children with asthma: why no progress?

PMID- 11241033
TI  - The 4 H Club: health, happiness, factor H, and HUS.

PMID- 11241034
TI  - Does influenza vaccination prevent asthma exacerbations in children?
AB  - OBJECTIVE: Influenza can exacerbate asthma, particularly in children. The
      effectiveness of influenza vaccine in preventing influenza-related asthma
      exacerbations, however, is not known. We evaluated influenza vaccine
      effectiveness in protecting children against influenza-related asthma
      exacerbations. STUDY DESIGN: We conducted a population-based retrospective cohort
      study with medical and vaccination records in 4 large health maintenance
      organizations in the United States during the 1993-1994, 1994-1995, and 1995-1996
      influenza seasons. We studied children with asthma who were 1 through 6 years of
      age and who were identified by search of computerized databases of medical
      encounters and pharmacy dispensings. Main outcome measures were exacerbations of
      asthma evaluated in the emergency department or hospital. RESULTS: Unadjusted
      rates of asthma exacerbations were higher after influenza vaccination than before
      vaccination. After adjustment was done for asthma severity by means of a self
      control method, however, the incidence rate ratios of asthma exacerbations after
      vaccination were 0.78 (95% CI: 0.55 to 1.10), 0.59 (0.43 to 0.81), and 0.65 (0.52
      to 0.80) compared with the period before vaccination during the 3 influenza
      seasons. CONCLUSIONS: After controlling for asthma severity, we found that
      influenza vaccination protects against acute asthma exacerbations in children.

PMID- 11241035
TI  - Detection of IgA and IgG but not IgE antibody to respiratory syncytial virus in
      nasal washes and sera from infants with wheezing.
AB  - BACKGROUND AND OBJECTIVE: The capacity of respiratory syncytial virus (RSV) to
      stimulate an IgE antibody response and enhance the development of atopy and
      asthma remains controversial. Nasal washes and sera from 40 infants (20 with
      wheezing, 9 with rhinitis, and 11 without respiratory tract symptoms) were
      obtained to measure IgE, IgA, and IgG antibody to the immunodominant, F and G,
      virion proteins from RSV. STUDY DESIGN: Children (aged 6 weeks to 2 years) were
      enrolled in the emergency department during the mid-winter months and seen at
      follow-up when they were asymptomatic. All nasal washes were tested for RSV
      antigen. Determinations of antibody isotypes (IgE, IgA, and IgG) to RSV antigens
      were done in nasal washes and sera by using an enzyme-linked immunosorbent assay.
      In a subset of nasal washes, IgE to RSV was also evaluated by using a monoclonal
      anti-F(c)E antibody-based assay. RESULTS: Fifteen patients with wheezing, two
      with rhinitis, and one control subject tested positive for RSV antigen at
      enrollment. Thirteen patients with wheezing were <6 months old, and most (77%)
      were experiencing their first attack. Among the children with positive test
      results for RSV antigen, an increase in both nasal wash and serum IgA antibody to
      RSV-F(a) and G(a) was observed at the follow-up visit. However, there was no
      evidence for an IgE antibody response to either antigen. CONCLUSION: Both IgA and
      IgG antibodies to the immunodominant RSV-F(a) and G(a) antigens were readily
      detected in the nasal washes and sera from patients in this study. We were unable
      to demonstrate specific IgE antibody to these antigens and conclude that the
      production of IgE as a manifestation of a T(H)2 lymphocyte response to RSV is
      unlikely.

PMID- 11241036
TI  - Prospective multicenter study of relapse after treatment for acute asthma among
      children presenting to the emergency department.
AB  - OBJECTIVE: Single-center studies have reported varying relapse rates after
      treatment of patients with acute asthma. We determined the relapse rate after
      emergency department (ED) treatment in a cohort of children. DESIGN: This was a
      prospective inception cohort study performed during 1997-1998. SETTING: The study
      was performed in 44 EDs including both general and pediatric centers. PATIENTS:
      Children (n = 1184) aged 2 to 17 years who had been admitted to EDs, with acute
      asthma restricted to 881 patients discharged from the ED. MAIN RESULTS: Two weeks
      after discharge, families were telephoned to determine relapse. Follow-up data
      were available for 762 (86%) of the children with a 10% incidence of relapse. On
      univariate analysis several factors were associated with relapse including
      current medications and markers of asthma severity. On multivariate analysis the
      factors associated with relapse were age (OR 1.4 per 5-year increase), use of
      second-line asthma medications (OR 3.7), exposure to cigarette smoke (OR 0.5),
      and ED visits within the past year (OR 1.2 per 5 ED visits). CONCLUSIONS: The
      incidence of relapse among children is lower than that observed among adults and
      varies with age. Other risk factors such as frequent ED visits are likely markers
      of chronic asthma severity. Further research should focus on ways to decrease the
      relapse rate among patients at high risk.

PMID- 11241038
TI  - Neurologic examination in infants with hypoxic-ischemic encephalopathy at age 9
      to 14 months: use of optimality scores and correlation with magnetic resonance
      imaging findings.
AB  - OBJECTIVES: To evaluate whether a structured and scorable neurologic examination
      (The Hammersmith Infant Neurological Examination) correlates with early magnetic
      resonance imaging findings in a group of infants with hypoxic-ischemic
      encephalopathy (HIE) and whether the scores of this assessment can predict the
      locomotor function in these children. STUDY DESIGN: A total of 53 term infants
      fulfilling the criteria for HIE underwent scanning within 4 weeks from delivery
      with a 1 Tesla HPQ magnet. The scores from the neurologic examination performed
      between 9 to 14 months were correlated to the neonatal magnetic resonance imaging
      findings and to the maximal locomotor function defined at the ages of 2 and 4
      years. RESULTS: The scores were always optimal in the infants with normal or
      minor neonatal magnetic resonance imaging findings. The lowest scores were
      associated with severe basal ganglia and white matter lesions. All the infants
      who had a global score between 67 and 78 at 1 year were able to walk
      independently at 2 years and without restrictions at 4 years. Scores between 40
      and 67 were associated with restricted mobility and scores <40 with severely
      limited self-mobility at 2 and 4 years. CONCLUSIONS: The use of a standardized
      neurologic optimality scoring system gives additional prognostic information,
      easily available in the clinic, on the severity of the functional motor outcome
      in infants with HIE.

PMID- 11241037
TI  - Early predictors of neurodevelopmental outcome in symptomatic congenital
      cytomegalovirus infection.
AB  - OBJECTIVE: To determine the ability of neonatal clinical, audiologic, and
      computed tomography (CT) findings to predict long-term neurodevelopmental outcome
      in children with symptomatic congenital cytomegalovirus (CMV) infection. METHODS:
      Longitudinal cohort study of children (n = 41) with symptomatic congenital CMV
      infection evaluated at birth and followed up with serial age-appropriate
      neurodevelopmental testing. The performance of birth characteristics as
      predictors of long-term outcome were determined, and clinical and CT scoring
      systems were developed and correlated with intellectual outcome. RESULTS:
      Microcephaly was the most specific predictor of mental retardation (100%; 95% CI
      84.5-100) and major motor disability (92.3%; 95% CI 74.8-99). An abnormality
      detected by CT was the most sensitive predictor for mental retardation (100%; 95%
      CI 82.3-100) and motor disability (100%; 95% CI 78.2-100). A highly significant
      (P <.001) positive correlation was found between head size at birth and the
      intelligence/developmental quotient (IQ/DQ). Approximately 29% of children had an
      IQ/DQ >90. There was no association between sensorineural hearing loss at birth
      and cognitive outcome. However, children with sensorineural hearing loss on
      follow-up (congenital and late-onset) had a lower IQ/DQ (P =.006) than those with
      normal hearing. CONCLUSIONS: The presence of microcephaly at birth was the most
      specific predictor of poor cognitive outcome in children with symptomatic
      congenital CMV infection, whereas children with normal findings on head CT and
      head circumference proportional to weight exhibited a good cognitive outcome.

PMID- 11241039
TI  - Sleep position and the use of soft bedding during bed sharing among African
      American infants at increased risk for sudden infant death syndrome.
AB  - Soft bedding increases the risk for death among prone infants. We compared the
      softness of beds and bedding and infant sleep position for infants sleeping alone
      and for those bed sharing. STUDY DESIGN: Questionnaires were used to record the
      bedding and sleep practices of 218 consecutive African American infants.
      Enrollment was prospective. Mechanical models were used in the homes of a
      subgroup to measure the softness of bedding and its propensity to cause
      rebreathing. Results were compared by using the Student t test, Mann-Whitney U
      test, and chi(2) analysis. RESULTS: In a cross-sectional sample of infants, at
      8.2 +/- 3.3 weeks of age, 61% (133 of 218) had bed shared > or =1 of the previous
      14 nights and 48.6% (106 of 218) had bed shared the night before. Breast-feeding
      rates were not different for bed sharers and those sleeping alone. The rates of
      maternal smoking for both groups were low (13.6% vs 11.8%). Comforters, pillows,
      and waterbeds were more commonly used beneath bed-sharing infants. Bed sharers
      were twice as likely to habitually be placed prone for sleep (18% vs 9%). In the
      subgroup studied in their homes (13 bed sharing, 19 alone), the shared beds were
      softer (P <.0001) and could cause more rebreathing (P =.007). CONCLUSIONS:
      Infants at increased risk for sudden infant death syndrome, by sociodemographic
      criteria, who also bed share are more likely to sleep prone and to use softer
      beds. These findings may explain part of the risk associated with bed sharing
      among US infants, a risk that appears to be independent of the effects of
      maternal smoking.

PMID- 11241040
TI  - Estimates of illicit drug use during pregnancy by maternal interview, hair
      analysis, and meconium analysis.
AB  - OBJECTIVE: To compare the sensitivity and specificity of maternal interview,
      maternal hair analysis, and meconium analysis in detecting perinatal exposure to
      cocaine, opiate, and cannabinoid. DESIGN/METHODS: The use of cocaine, opiate, and
      cannabinoid during pregnancy was determined prospectively in 58 women by 3
      methods: structured maternal interview, maternal hair analysis, and meconium
      analyses. The results of the 3 methods were compared with one another. RESULTS:
      The maternal interview showed the lowest sensitivity in detecting cocaine and
      opiate exposures (65% and 67%, respectively), but it had the highest sensitivity
      in detecting cannabinoid exposure (58%). Both hair and meconium analyses had high
      sensitivity for detecting cocaine or opiate exposures. Hair analysis had a
      sensitivity of 100% for cocaine and 80% for opiate detection. However, it had a
      false-positive rate of 13% for cocaine and 20% for opiate, probably as a result
      of passive exposure. Meconium analysis had a sensitivity of 87% for cocaine and
      77% for opiate detection, but unlike hair analysis, it had no false-positive test
      results for cocaine. Both hair and meconium analyses had low sensitivity in
      detecting cannabinoid exposure (21%-22.7%), most probably because of the sporadic
      use of cannabinoid. CONCLUSION: Meconium and hair analyses had the highest
      sensitivities for detecting perinatal use of cocaine and opiate, but not for
      cannabinoid. The principal drawback of hair analysis is its potential for false
      positive test results associated with passive exposure to drugs. Maternal
      interview is a time-consuming test of low sensitivity. The high sensitivity of
      meconium analysis and the ease of collection make this test ideal for perinatal
      drug screening.

PMID- 11241041
TI  - Echocardiographic outcome of infants treated as newborns with inhaled nitric
      oxide for severe hypoxemic respiratory failure.
AB  - OBJECTIVE: To determine the cardiovascular outcome of a group of term newborns
      treated with inhaled nitric oxide (iNO) for severe hypoxemic respiratory failure
      with associated persistent pulmonary hypertension. STUDY DESIGN: We performed
      echocardiographic evaluations in 40 survivors treated for severe neonatal
      hypoxemic respiratory failure. Each of the 40 had at least 2 follow-up
      echocardiograms at 3 or 6 and 24 months. These studies were compared with
      echocardiograms done in infants in a normal, age-matched control group. RESULTS:
      Three of 31 infants met echocardiographic criteria for pulmonary hypertension at
      the 3-month examination. Two of the 3 had associated structural heart disease (1
      with an atrial septal defect and 1 with a ventricular septal defect). At 24
      months only 1 patient had pulmonary hypertension. This infant had an atrial
      septal defect that was surgically closed shortly after the 24-month
      echocardiogram because of the pulmonary hypertension. Group comparisons of 3- and
      24-month echocardiographic variables showed no differences between the study and
      control groups. In the 31 infants in whom serial studies were completed, expected
      age-related changes were demonstrated between the 3- and 24-month examinations.
      CONCLUSIONS: The incidence of residual pulmonary hypertension in infants treated
      as newborns for severe hypoxemic respiratory failure is low. The group at highest
      risk is those with structural heart disease.

PMID- 11241042
TI  - Gastroesophageal reflux medications in the treatment of apnea in premature
      infants.
AB  - OBJECTIVE: To determine whether medications commonly used in the management of
      gastroesophageal reflux reduce the frequency of apnea in premature infants. STUDY
      DESIGN: We reviewed the medical records of all infants </=36 weeks' gestational
      age at birth who were treated in 2 neonatal intensive care units from 1990
      through 1999 and identified those who received the antireflux medications
      cisapride or metoclopramide in association with apnea. We averaged the frequency
      of apnea during the 5 days before and the 5 days after antireflux treatment was
      started and compared these 2 periods by paired analysis. RESULTS: There were 164
      separate courses of treatment with either cisapride or metoclopramide in 132
      patients. There were 3.6 +/- 3.2 apneic episodes per day during the 5 days before
      treatment and 4.0 +/- 3.4 apneic episodes per day during the 5 days after
      treatment (P =.048). When evaluated separately, neither cisapride nor
      metoclopramide reduced the frequency of apnea. Stratification for documented
      reflux (by radiographic contrast or by pH probe analysis), concomitant use of
      methylxanthines or ranitidine, developmental age, feeding volume, and respiratory
      support did not identify a subgroup of patients whose apnea improved with
      antireflux treatment. CONCLUSION: Antireflux medications do not reduce the
      frequency of apnea in premature infants.

PMID- 11241043
TI  - Efficacy of Lactobacillus GG in prevention of nosocomial diarrhea in infants.
AB  - OBJECTIVE: Nosocomial diarrhea is a major problem in pediatric hospitals
      worldwide. We evaluated the efficacy of orally administered Lactobacillus GG
      (LGG) in the prevention of this disease in young children. STUDY DESIGN: Eighty
      one children aged 1 to 36 months who were hospitalized for reasons other than
      diarrhea were enrolled in a double-blind trial and randomly assigned at admission
      to receive LGG (n = 45) at a dose of 6 x 10(9) colony-forming units or a
      comparable placebo (n = 36) twice daily orally for the duration of their hospital
      stay. RESULTS: LGG reduced the risk of nosocomial diarrhea (> or =3 loose or
      watery stools/24 h) in comparison with placebo (6.7% vs 33.3%; relative risk:
      0.2; [95% CI: 0.06-0.6]; number needed to treat: 4 [95% CI: 2-10]). The
      prevalence of rotavirus infection was similar in LGG and placebo groups (20% vs
      27.8%, respectively; relative risk: 0.72; 95% CI: 0.33-1.56). However, the use of
      LGG compared with placebo significantly reduced the risk of rotavirus
      gastroenteritis (1/45 [2.2%] vs 6/36 [16.7%], respectively; relative risk: 0.13;
      95% CI: 0.02-0.79; number needed to treat: 7; 95% CI: 3-40). CONCLUSIONS:
      Prophylactic use of LGG significantly reduced the risk of nosocomial diarrhea in
      infants, particularly nosocomial rotavirus gastroenteritis.

PMID- 11241044
TI  - Colonic CD8 and gamma delta T-cell infiltration with epithelial damage in
      children with autism.
AB  - OBJECTIVES: We have reported colitis with ileal lymphoid nodular hyperplasia
      (LNH) in children with regressive autism. The aims of this study were to
      characterize this lesion and determine whether LNH is specific for autism.
      METHODS: Ileo-colonoscopy was performed in 21 consecutively evaluated children
      with autistic spectrum disorders and bowel symptoms. Blinded comparison was made
      with 8 children with histologically normal ileum and colon, 10 developmentally
      normal children with ileal LNH, 15 with Crohn's disease, and 14 with ulcerative
      colitis. Immunohistochemistry was performed for cell lineage and functional
      markers, and histochemistry was performed for glycosaminoglycans and basement
      membrane thickness. RESULTS: Histology demonstrated lymphocytic colitis in the
      autistic children, less severe than classical inflammatory bowel disease.
      However, basement membrane thickness and mucosal gamma delta cell density were
      significantly increased above those of all other groups including patients with
      inflammatory bowel disease. CD8(+) density and intraepithelial lymphocyte numbers
      were higher than those in the Crohn's disease, LNH, and normal control groups;
      and CD3 and plasma cell density and crypt proliferation were higher than those in
      normal and LNH control groups. Epithelial, but not lamina propria,
      glycosaminoglycans were disrupted. However, the epithelium was HLA-DR(-),
      suggesting a predominantly T(H)2 response. INTERPRETATION: Immunohistochemistry
      confirms a distinct lymphocytic colitis in autistic spectrum disorders in which
      the epithelium appears particularly affected. This is consistent with increasing
      evidence for gut epithelial dysfunction in autism.

PMID- 11241045
TI  - Postictal cerebrospinal fluid abnormalities in children.
AB  - OBJECTIVES: To determine the frequency and characteristics of seizure-induced
      cerebrospinal fluid (CSF) abnormalities in children and to identify potential
      alternative causes of these findings. METHODS: Consecutive patients (n = 80) who
      underwent lumbar puncture within 24 hours after a seizure were studied
      retrospectively. The presence of CSF abnormalities in total leukocytes,
      polymorphonuclear cells, and protein was determined by using age-specific
      reference values. Coexisting conditions that could affect CSF findings, such as
      traumatic lumbar puncture, concurrent neurologic disease, and undiagnosed
      meningitis, were identified. RESULTS: Eighteen of the 80 patients were excluded
      from the final study group because of the presence of another condition that
      could alter the CSF. More than 50% of the excluded patients had an abnormal CSF
      leukocyte count or protein level, including 2 patients with initially undiagnosed
      meningitis, which was subsequently detected by post-hoc polymerase chain reaction
      testing. In the remaining 62 patients, postictal pleocytosis was detected in only
      3 (5%), and increased protein was detected in only 6 (10%). The maximal postictal
      pleocytosis and protein level were 8 x 10(6) leukocytes/L (8 leukocytes/mm(3))
      and 0.52 g/L (52 mg/dL), respectively. CONCLUSIONS: Seizure-induced CSF
      abnormalities are rare in children, and alternative, often unidentified, disease
      processes may account for many observed postictal abnormalities. All patients
      with abnormal CSF after a seizure should be thoroughly evaluated for other causes
      of the abnormality.

PMID- 11241046
TI  - Decreased urinary citrate excretion in type 1a glycogen storage disease.
AB  - OBJECTIVES: To quantify urinary citrate and calcium excretion and systemic acid
      base status in patients with type 1a glycogen storage disease (GSD1a) and to
      investigate their relationship to renal complications. STUDY DESIGN: Fifteen
      patients (7 male and 8 female; age range, 3--28 years) were studied during annual
      evaluations of metabolic control. All were treated with intermittent doses of
      uncooked cornstarch. Hourly blood sampling and a 24-hour urine collection were
      obtained while subjects followed their usual home dietary regimen. RESULTS: All
      but the youngest subject had low levels of citrate excretion (mean 2.4 +/- 1.8
      mg/kg/d; 129 +/- 21 mg citrate/g creatinine). Normally, urinary citrate excretion
      increases with age; however, in patients with GSD1a, a strong inverse exponential
      relationship was found between age and citrate excretion (r = -0.84, P <.0001).
      Urinary citrate excretion was unrelated to markers of metabolic control.
      Hypercalciuria occurred in 9 of 15 patients (mean urinary calcium/creatinine
      ratio, 0.27 +/- 0.15) and was also inversely correlated with age (r = -0.62, P
      =.001). CONCLUSIONS: Hypocitraturia that worsens with age occurs in metabolically
      compensated patients with GSD1a. The combination of low citrate excretion and
      hypercalciuria appears to be important in the pathogenesis of nephrocalcinosis
      and nephrolithiasis. Citrate supplementation may be beneficial in preventing or
      ameliorating nephrocalcinosis and the development of urinary calculi in GSD1a.

PMID- 11241047
TI  - Protein-sensitive and fasting hypoglycemia in children with the
      hyperinsulinism/hyperammonemia syndrome.
AB  - OBJECTIVE: Because the hyperinsulinism/hyperammonemia (HI/HA) syndrome is
      associated with gain of function mutations in the leucine-stimulated insulin
      secretion pathway, we examined whether protein feeding or fasting was responsible
      for hypoglycemia in affected patients. STUDY DESIGN: Patients with HI/HA (8
      children and 6 adults) were studied. All had dominantly expressed mutations of
      glutamate dehydrogenase and plasma concentrations of ammonium that were 2 to 5
      times normal. The responses to a 24-hour fasting test were determined in 7
      patients. Responses to a 1.5 gm/kg oral protein tolerance test in 12 patients
      were compared with responses of 5 control subjects. RESULTS: The median age at
      onset of hypoglycemia in the 14 patients was 9 months; diagnosis was delayed
      beyond age 2 years in 6 patients, and 4 were not given a diagnosis until
      adulthood. Fasting tests revealed unequivocal evidence of hyperinsulinism in only
      1 of 7 patients. Three did not develop hypoglycemia until 12 to 24 hours of
      fasting; however, all 7 demonstrated inappropriate glycemic responses to glucagon
      that were characteristic of hyperinsulinism. In response to oral protein, all 12
      patients with HI/HA showed a fall in blood glucose compared with none of 5
      control subjects. Insulin responses to protein loading were similar in the
      patients with HI/HA and control subjects. CONCLUSION: The postprandial blood
      glucose response to a protein meal is more sensitive than prolonged fasting for
      detecting hypoglycemia in the HI/HA syndrome.

PMID- 11241048
TI  - Caveats when considering ketogenic diets for the treatment of pyruvate
      dehydrogenase complex deficiency.
AB  - OBJECTIVES: We conducted a critical assessment of the use of diets high in fat
      and low in carbohydrate ("ketogenic") in the treatment of children with
      congenital lactic acidosis caused by mutations in the mitochondrial pyruvate
      dehydrogenase complex (PDC). STUDY DESIGN: The dietary composition of 18 subjects
      (11 from literature sources and 7 previously unpublished cases) was analyzed for
      nutrient composition. The biochemical and clinical responses to a long-term
      ketogenic regimen were also evaluated. RESULTS: There was lack of uniformity in
      the proportion of fat calories administered and in the fatty acid composition of
      the diets. Ketogenic diets are also generally high in protein, compared with the
      recommended dietary allowance for age. Patient response to these regimens also
      varied considerably. CONCLUSIONS: Although ketogenic diets have become the
      standard of care for the treatment of PDC deficiency, data to support their use
      are based on a few uncontrolled case reports in which dietary composition varied
      widely. Furthermore, there are several theoretical reasons for concern about the
      long-term safety of high-fat, low-carbohydrate diets. A controlled, prospective
      evaluation of the risks and benefits of these regimens for patients with PDC
      deficiency is required to establish rational nutritional guidelines.

PMID- 11241049
TI  - Molecular prenatal diagnosis in families with fetal mitochondrial trifunctional
      protein mutations.
AB  - OBJECTIVES: To evaluate the feasibility of molecular prenatal diagnosis in
      families with mitochondrial trifunctional protein (TFP) mutations and
      prospectively study the effects of fetal genotype on pregnancy outcome. TFP
      catalyzes the last 3 steps in mitochondrial long-chain fatty acid oxidation.
      STUDY DESIGN: We performed molecular prenatal diagnosis in 9 pregnancies, 8 in 6
      families with isolated long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD)
      deficiency and one in a family with complete TFP deficiency. Analyses were
      performed on chorionic villous samples in 7 pregnancies and on amniocytes in 2.
      RESULTS: Molecular prenatal diagnosis successfully identified the fetal genotype
      in all 9 pregnancies. Two fetuses were affected, and both pregnancies were
      terminated by family decision. Two other fetuses had normal genotype and 5 others
      were heterozygotes. These 7 pregnancies were uncomplicated, and all the offspring
      are alive and apparently healthy. Genotypes of the aborted fetuses and neonates
      were confirmed by molecular analysis and enzymatic assays. CONCLUSIONS: Molecular
      prenatal diagnosis is possible and valid in guiding management of pregnancies in
      families with known TFP defects. Women heterozygous for TFP alpha-subunit
      mutations who carry fetuses with wild-type or heterozygous genotypes have
      uncomplicated pregnancies.

PMID- 11241050
TI  - Cardiovascular risk factors after Kawasaki disease: a case-control study.
AB  - OBJECTIVES: To determine cardiovascular risk profiles of patients with Kawasaki
      disease and to relate them to a noninvasive measure of endothelial function.
      STUDY DESIGN: Case-control study. Cardiovascular risk assessment including
      brachial artery reactivity was performed in 24 patients 11.3 +/- 1.8 (mean +/-
      SD) years after Kawasaki disease and in 11 subjects in a normal control group.
      RESULTS: The case versus control groups were similar regarding age, sex, race,
      body mass index, and percentage of ideal body weight, although cases had a higher
      mean z score of body mass index than normal (+1.00 +/- 1.18; P <.001). Cases had
      normal fasting total cholesterol levels but a higher mean z score of triglyceride
      levels (+1.35 +/- 2.04; P <.004). The case group had significantly higher mean
      systolic and diastolic resting blood pressure z scores (+0.76 +/- 1.06; P <.01
      and +0.96 +/- 1.19; P <.01, respectively) than the control group and population
      norms. Endothelial function as indicated by brachial artery reactivity was not
      significantly different between the case versus control groups. In the case group
      higher blood pressure, increasing adiposity, and higher fasting triglyceride
      levels were significantly interrelated but did not relate to brachial artery
      reactivity or coronary artery abnormalities. CONCLUSIONS: Patients after Kawasaki
      disease tend to have a more adverse cardiovascular risk profile potentially
      indicative of an increased predisposition to premature atherosclerotic changes.

PMID- 11241051
TI  - Effect of growth hormone treatment on testicular function, puberty, and
      adrenarche in boys with non-growth hormone-deficient short stature: a randomized,
      double-blind, placebo-controlled trial.
AB  - OBJECTIVE: To evaluate the effect of growth hormone (GH) therapy on pubertal
      onset, pubertal pace, adult testicular function, and adrenarche in boys with non
      GH-deficient short stature. STUDY DESIGN: Randomized, double-blind, placebo
      controlled trial. GH (0.074 mg/kg, subcutaneously, 3 times per week) or placebo
      treatment was initiated in prepubertal or early pubertal boys and continued until
      near final height was reached (n = 49). Statistical significance was assessed by
      survival analysis, repeated-measures analysis of variance, and Student t test.
      RESULTS: GH therapy did not affect the age at pubertal onset, defined either by
      testicular volume >4 mL or by testosterone concentration >1.0 nmol/L (30 ng/dL).
      GH treatment also did not affect the pace of puberty, defined either by the rate
      of change in testicular volume or testosterone concentration during the 4 years
      after pubertal onset. In boys followed up to age > or =16 years during the study,
      there were no significant differences in final testicular volume or in plasma
      testosterone, luteinizing hormone, or follicle-stimulating hormone
      concentrations. The pace of adrenarche, assessed by change in
      dehydroepiandrosterone sulfate levels over time, also did not differ
      significantly between the GH and placebo groups. CONCLUSION: Our findings suggest
      that GH treatment does not cause testicular damage, alter the onset or pace of
      puberty, or alter the pace of adrenarche in boys with non-GH-deficient short
      stature.

PMID- 11241052
TI  - Hypoparathyroidism and intracranial calcifications in beta-thalassemia major.

PMID- 11241054
TI  - Moyamoya disease complicated with renal artery stenosis and nephrotic syndrome:
      reversal of nephrotic syndrome after nephrectomy.
AB  - A 7-year-old boy with moyamoya disease developed sustained hypertension,
      nephrotic syndrome, hyperreninemia, and occlusion of the right renal artery.
      After right nephrectomy, hyperreninemia and hypertension improved. Proteinuria
      was resolved after nephrectomy, in parallel with the decrease in plasma renin
      activity. Moyamoya disease can cause nephrotic-range proteinuria, which is caused
      hemodynamically by hyperreninemia.

PMID- 11241053
TI  - Familial hemolytic uremic syndrome associated with complement factor H
      deficiency.
AB  - Atypical hemolytic uremic syndrome (HUS) associated with factor H deficiency
      (FHD) carries a poor prognosis. A 3-year-old girl with FHD-HUS reached end-stage
      renal disease at age 6 months after experiencing numerous relapses; she underwent
      a cadaveric renal transplant at age 46 months. One month after transplantation,
      she experienced an extensive non-hemorrhagic cerebral infarction. Later,
      hematologic and renal manifestations of HUS developed, followed by another
      massive cerebral infarction and death in spite of multiple plasma transfusions. A
      14-month-old boy with FHD-HUS experienced numerous HUS episodes starting at the
      age of 2 weeks. Daily plasma transfusions during relapses brought about only a
      temporary state of remission. However, prophylactic twice-weekly plasma therapy
      has been successful in preventing relapses and preserving renal function. With
      this regimen, serum factor H was increased from 6 mg/dL to subnormal values of 12
      to 25 mg/dL (normal >60 mg/dL). We conclude that FHD-HUS recurs because FHD is
      not corrected by renal transplantation. A hypertransfusion protocol may prevent
      FHD-HUS.

PMID- 11241055
TI  - Germline Wilms tumor suppressor gene (WT1) mutation leading to isolated genital
      malformation without Wilms tumor or nephropathy.
AB  - Mutations of the Wilms tumor suppressor gene (WT1 ) have been described only in
      patients with syndromes associated with urogenital malformation and Wilms tumor
      or nephropathy. We present a male patient with an isolated genital malformation
      caused by a WT1 mutation.

PMID- 11241056
TI  - Isolated diffuse mesangial sclerosis and Wilms tumor suppressor gene.
AB  - Diffuse mesangial sclerosis is a rare renal disease, occurring either in
      isolation or as part of Denys-Drash syndrome. Denys-Drash syndrome originates
      from mutations of the Wilms tumor suppressor gene (WT1 ). We describe the
      presence of WT1 mutations in 7 Japanese children with isolated diffuse mesangial
      sclerosis.

PMID- 11241057
TI  - Fasting hypoglycemia is common during maintenance therapy for childhood acute
      lymphoblastic leukemia.
AB  - Nineteen of 35 children (54%) with acute lymphoblastic leukemia receiving
      maintenance therapy consisting of daily oral 6-mercaptopurine and weekly oral
      methotrexate developed hypoglycemia (blood glucose level <2.7 mmol/L [50 mg/dL]
      or <2.9 mmol/L [54 mg/dL] with symptoms) during 16 hours of overnight fasting. In
      15 of 15 re-studied children, fasting tolerance had improved, and in 67% (10/15),
      it had become normal a few months after cessation of therapy.

PMID- 11241058
TI  - Successful living-donor liver transplantation from an asymptomatic carrier mother
      in ornithine transcarbamylase deficiency.
AB  - A liver transplantation from an asymptomatic mother, who was a carrier of
      ornithine transcarbamylase deficiency, to her daughter, who had severe
      manifestation, was successfully performed. One-year monitoring of plasma amino
      acid and urinary orotate/orotidine levels revealed no abnormality in the urea
      cycle in either subject.

PMID- 11241059
TI  - Retropharyngeal abscess: epiglottitis of the new millennium.
AB  - From 1993 through 1999, 26 children with retropharyngeal abscess and 2 children
      with acute epiglottitis were cared for by pediatric otolaryngologists in northern
      Virginia. Fever, sore throat, dysphagia, refusal to swallow, dysphonia, drooling,
      and neck extension are common presenting signs and symptoms in acute epiglottitis
      and in retropharyngeal abscess. Contrast-enhanced computed tomography of the
      oropharynx was performed in all cases and was the most helpful diagnostic test.

PMID- 11241060
TI  - Fiberoptic and conventional phototherapy effects on the skin of premature
      infants.
AB  - To evaluate the effects of conventional phototherapy and fiberoptic phototherapy
      on trans-epidermal water loss in preterm infants with and without skin ointment
      application, 20 infants were randomly assigned to receive conventional or
      fiberoptic phototherapy for non-hemolytic hyperbilirubinemia. After conventional
      phototherapy, there were no significant differences in trans-epidermal water loss
      between ointment-treated and untreated areas. After fiberoptic phototherapy,
      trans-epidermal water loss significantly increased from ointment-treated and
      untreated areas, but the increase was less in treated areas.

PMID- 11241061
TI  - Ophthalmic drops causing coma in an infant.
AB  - A 1-month-old infant with Peters anomaly had recurrent episodes of
      unresponsiveness, hypotension, hypotonia, hypothermia, and bradycardia. An
      extensive medical evaluation determined these episodes to be caused by
      brimonidine, an anti-glaucoma agent. There is the potential for serious toxic
      effects from the systemic absorption of topically applied ophthalmic agents in
      children.

PMID- 11241062
TI  - Mandibular frenulum as a sign of infantile hypertrophic pyloric stenosis.

PMID- 11241064
TI  - Why we need sedation guidelines.

PMID- 11241065
TI  - Premature thelarche in girls after growth hormone therapy.

PMID- 11241067
TI  - Auxiliary liver transplantation for toxic mushroom poisoning.

PMID- 11241071
TI  - L-dopa and selegiline for tyrosine hydroxylase deficiency.

PMID- 11241069
TI  - Mercury toxicity.

PMID- 11241072
TI  - Statewide reporting of coronary artery surgery results: a view from California.

PMID- 11241073
TI  - Mechanical Cardiac Support 2000: Current applications and future trial design.

PMID- 11241074
TI  - Cerebral protection during aortic arch surgery.

PMID- 11241075
TI  - Calcification of bioprosthetic heart valves and its assessment.

PMID- 11241076
TI  - Arterial grafts for coronary surgery: vasospasm and patency rate.

PMID- 11241077
TI  - Ethical implications of heart transplantation in elderly patients.

PMID- 11241079
TI  - Pulmonary resection for multi-drug resistant tuberculosis.
AB  - OBJECTIVES: Mycobacterium tuberculosis continues to be a major cause of morbidity
      and mortality throughout the world. Complacency by the medical profession and by
      patients has caused a new strain of Mycobacterium tuberculosis to emerge that is
      highly resistant to current antibiotics. The possibility of a new worldwide
      epidemic of drug-resistant Mycobacterium tuberculosis is of concern. Optimal
      therapy for patients infected with multi-drug resistant tuberculosis often
      requires surgical intervention to eradicate the infection. We report on our
      experience with pulmonary resection for multi-drug resistant tuberculosis.
      METHODS: During a 17-year period, 172 patients underwent 180 pulmonary
      resections. All patients had multi-drug resistant tuberculosis and had a minimum
      of 3 months of medical therapy before surgery. Muscle flaps were frequently used
      to avoid residual space and bronchial stump problems. RESULTS: During the study
      period, 98 lobectomies and 82 pneumonectomies were performed. Eight patients
      underwent multiple procedures. Operative mortality was 3.3% (6/180). Three
      patients died of respiratory failure, 2 patients died of a cerebrovascular
      accident, and 1 patient had a myocardial infarction. Late mortality was 6.8%
      (11/166). Significant morbidity was 12% (20/166). One half (91) of the patients
      had positive sputum at the time of surgery. After the operation, the sputum
      remained positive in only 4 (2%) patients. Mean length of follow-up was 7.6 years
      (range 4-204 months). CONCLUSIONS: Surgery remains an important adjunct to
      medical therapy for the treatment of multi-drug resistant Mycobacterium
      tuberculosis. In the setting of localized disease, persistent sputum positivity,
      or patient intolerance of medical therapy, pulmonary resection should be
      undertaken. Pulmonary resection for multi-drug resistant tuberculosis can be
      performed with acceptable operative morbidity and mortality.

PMID- 11241078
TI  - Subdiaphragmatic venous hemodynamics in the Fontan circulation.
AB  - OBJECTIVE: We investigated the subdiaphragmatic venous physiology in patients
      subjected to the Fontan operation to understand some of the early and late
      problems of this circulation. METHODS: Flows were evaluated by Doppler
      ultrasonography in the subhepatic inferior vena cava, hepatic vein, and portal
      vein during respiratory monitoring and with a tilt table. Twenty control subjects
      (group A) and 56 patients who had the Fontan operation, 27 in functional class I
      (group B) and 29 in class III or IV (group C), were studied.
      Inspiratory/expiratory flow ratio was calculated to reflect respiratory effects,
      and upright/supine flow ratio was calculated to assess gravity effects. Inferior
      vena caval, hepatic venous, and wedged hepatic venous pressures were measured
      during catheterization in 21 control subjects and 25 Fontan patients. The
      difference between wedged and hepatic venous pressures represents the
      transhepatic venous pressure gradient. RESULTS: Fontan hepatic venous flow
      depended more on inspiration than control, but without difference between groups
      B and C (inspiratory/expiratory flow ratios: 1.7, 2.9, and 2.9, respectively; P
      <.02). Normal portal venous flow was higher in expiration; this effect was lost
      in group B and reversed in group C (inspiratory/expiratory flow ratios: 0.8, 1.0,
      and 1.3; P <.0005). Gravity reduced portal venous flow in groups A and B, but
      progression to functional class III or IV (group C) exacerbated this effect
      (upright/supine flow ratios: 0.8, 0.7, and 0.5; P <.01). Inferior vena caval,
      hepatic venous, and wedged hepatic venous pressures (in millimeters of mercury)
      in the Fontan groups were all elevated compared with the control group (inferior
      vena cava, 14.4 +/- 4.4 vs 5.9 +/- 2.3; hepatic vein, 14.7 +/- 4.5 vs 5.9 +/-
      1.9; wedged hepatic vein, 14.7 +/- 4.0 vs 8.3 +/- 2.6; P <.0001). However,
      transhepatic venous pressure gradient in the Fontan group was lower than in the
      control group (0.5 +/- 0.5 vs 2.4 +/- 2.0; P <.001). Univariate analysis of
      inferior vena caval pressure and transhepatic venous pressure gradient showed
      significant inverse correlation (r = 0.6, P <.002). CONCLUSIONS: In patients who
      are in functionally poorer condition after the Fontan operation, portal venous
      flow loses normal expiratory augmentation and adverse gravity influence is
      enhanced. These suboptimal flow dynamics, coupled with higher splanchnic venous
      pressures and lower transhepatic venous pressure gradients, suggest that hepatic
      sinusoids are congested, acting as "open tubes." Transhepatic gradient loss is
      incrementally worse with higher caval pressures. These observations may be
      responsible for late gastrointestinal problems in patients who have had the
      Fontan operation.

PMID- 11241080
TI  - N1 esophageal carcinoma: the importance of staging and downstaging.
AB  - OBJECTIVE: To evaluate the effects of clinical staging and downstaging by
      induction chemoradiation therapy in patients with N1 esophageal carcinoma.
      METHODS: Sixty-nine consecutive patients with regional lymph node metastases
      (cN1) according to clinical staging received induction therapy before surgery.
      These were compared to 75 patients both clinically and pathologically N1
      (cN1/pN1) who underwent surgery without induction therapy and 79 patients
      clinically and pathologically not N1 (cN0/pN0) who underwent surgery without
      induction therapy. Analyses focused on survival and the cost and benefit of
      therapy. RESULTS: For comparison, the extremes of 5-year survival were 69% for
      cN0/pN0 patients who underwent surgery alone and 12% for cN1/pN1 patients who
      underwent surgery alone. Of 69 patients who received induction therapy, 37 were
      pN0 at resection (downstaged); they had an intermediate survival of 37% at 5
      years. Those patients not downstaged with induction therapy had a 12% 5-year
      survival, similar to patients with cN1/pN1 who underwent surgery alone. After
      adjusting for the strongest predictors of poor outcome, pN1, and increasing N1
      burden, a modest increased risk of death after induction therapy was identified.
      However, this cost of induction therapy was more than counterbalanced by the
      benefit of improved survival of downstaging to pN0. CONCLUSIONS: (1) pN1 is the
      strongest determinant of poor outcome. (2) cN1 patients who are downstaged by
      induction chemoradiation therapy to pN0 have an intermediate outcome. (3) cN1
      patients who are not downstaged by induction therapy have a poor outcome.

PMID- 11241081
TI  - Resection for bronchogenic carcinoma involving the carina: long-term results and
      effect of nodal status on outcome.
AB  - OBJECTIVE: Bronchogenic carcinoma in close proximity to or involving the carina
      remains a challenging problem for thoracic surgeons. The operative procedures to
      allow complete resection are technically demanding and can be associated with
      significant morbidity and mortality. Little is known about long-term survival
      data to guide therapy in these patients. METHODS: We conducted a single
      institution retrospective review. RESULTS: We have performed 60 carinal
      resections for bronchogenic carcinoma: 18 isolated carinal resections for tumor
      confined to the carinal or proximal main stem bronchus; 35 carinal
      pneumonectomies; 5 carinal plus lobar resections, and 2 carinal resections for
      stump recurrence after prior pneumonectomy. Thirteen patients (22%) had a history
      of lung or airway surgery. The overall operative mortality was 15%, improved from
      the first half of the series (20%) to the second half (10%), and varied according
      to the type of resection performed. Adult respiratory distress syndrome was
      responsible for 5 early deaths, and all late deaths were related to anastomotic
      complications. In 34 patients, all lymph nodes were negative for metastatic
      disease; 15 patients had positive N1 nodes, and 11 patients had positive N2/N3
      nodes. Complete follow-up was accomplished in 90%, with a mean follow-up of 59
      months. The overall 5-year survival including operative mortality was 42%, with
      19 absolute 5-year survivors. Survival was highest after isolated carinal
      resection (51%). Lymph node involvement had a strong influence on survival:
      patients without nodal involvement had a 5-year survival of 51%, compared with
      32% for patients with N1 disease and 12% for those with N2/N3 disease.
      CONCLUSIONS: This constitutes one of the largest single-institution reports on
      carinal resection for bronchogenic carcinoma involving the carina. Morbidity and
      mortality rates are acceptable. The overall survival including operative
      mortality is 42%. Positive N2/N3 lymph nodes may be a contraindication to surgery
      because of poor prognosis.

PMID- 11241082
TI  - Induction chemoradiation and surgical resection for non-small cell lung
      carcinomas of the superior sulcus: Initial results of Southwest Oncology Group
      Trial 9416 (Intergroup Trial 0160).
AB  - OBJECTIVE: The rate of complete resection (50%) and the 5-year survival (30%) for
      non-small cell lung carcinomas of the superior sulcus have not changed for 40
      years. Recently, combined modality therapy has improved outcome in other subsets
      of locally advanced non-small cell lung carcinoma. This trial tested the
      feasibility of induction chemoradiation and surgical resection in non-small cell
      lung carcinoma of the superior sulcus with the ultimate aim of improving
      resectability and survival. METHODS: Patients with mediastinoscopy-negative T3-4
      N0-1 superior sulcus non-small cell lung carcinoma received 2 cycles of cisplatin
      and etoposide chemotherapy concurrent with 45 Gy of radiation. Patients with
      stable or responding disease underwent thoracotomy 3 to 5 weeks later. All
      patients received 2 more cycles of chemotherapy and were followed up by serial
      radiographs and scans. Survival was calculated by the Kaplan-Meier method and
      prognostic factors were assessed for significance by Cox regression analysis.
      RESULTS: From April 1995 to September 1999, 111 eligible patients (77 men, 34
      women) were entered in the study, including 80 (72.1%) with T3 and 31 with T4
      tumors. Induction therapy was completed as planned in 102 (92%) patients. There
      were 3 treatment-related deaths (2.7%). Cytopenia was the main grade 3 to 4
      toxicity. Of 95 patients eligible for surgery, 83 underwent thoracotomy, 2 (2.4%)
      died postoperatively, and 76 (92%) had a complete resection. Fifty-four (65%)
      thoracotomy specimens showed either a pathologic complete response or minimal
      microscopic disease. The 2-year survival was 55% for all eligible patients and
      70% for patients who had a complete resection. To date, survival is not
      significantly influenced by patient sex, T status, or pathologic response.
      CONCLUSIONS: (1) This combined modality treatment is feasible in a multi
      institutional setting; (2) the pathologic complete response rates were high; and
      (3) resectability and overall survival were improved compared with historical
      experience, especially for T4 tumors, which usually have a grim prognosis.

PMID- 11241083
TI  - Completion pneumonectomy: current indications, complications, and results.
AB  - OBJECTIVE: Completion pneumonectomy is reported to be associated with high
      morbidity and mortality, especially when done in patients with benign disease. We
      review our 9 years of experience with this operation to evaluate the
      postoperative outcome and long-term results of various indications. METHODS:
      Between January 1990 and December 1998, 66 consecutive patients underwent
      completion pneumonectomy (6.8% of all pneumonectomies), and their cases were
      retrospectively reviewed. The indication was benign disease in 17 patients and
      malignant disease in 49 patients. In patients with malignant indications there
      were 14 local recurrences, 4 second primary tumors, 5 metastatic diseases, and 26
      indications because of incomplete initial resection. RESULTS: There were no
      intraoperative deaths, and the postoperative mortality rate was 7.6%.
      Complications were encountered in 32 (53%) patients, without any significant
      difference between benign indication (71%) and malignant indication (47%; P
      =.0923). Bronchopleural fistula was encountered in 5 (7.6%) patients, and empyema
      was encountered in 7 (11%) patients. The actuarial 5-year survival was 57% for
      all patients, 65% for those with benign indications, and 54% for those with
      malignant indications (60% for local recurrence, 50% for second primary tumor,
      and 56% for incomplete resection), without any difference between benign and
      malignant indications (P =.9478). CONCLUSIONS: Completion pneumonectomy can be
      performed with acceptable mortality and morbidity, even in patients with benign
      disease. Patients with preoperative infection can be managed with bronchial stump
      covering and adequate postoperative drainage. Although complications are common,
      they can successfully be managed with a proper understanding of them.

PMID- 11241084
TI  - Improved results of atherosclerotic arch aneurysm operations with a refined
      technique.
AB  - OBJECTIVE: We sought to analyze the postoperative hospital mortality and
      postoperative neurologic dysfunction in patients who had total arch replacement
      for atherosclerotic arch aneurysms using our recent refined technique. METHODS:
      Between June 1997 and April 2000, 50 consecutive patients underwent total arch
      replacement with an aortic arch branched graft for atherosclerotic arch
      aneurysms. Their mean age was 71 +/- 7 years (range, 57-87 years). Forty-eight
      (96%) patients were operated on electively, and the remaining 2 (4%) were
      operated on an emergency basis because of rupture of aneurysm. All operations
      were performed with hypothermic extracorporeal circulation, selective cerebral
      perfusion for cerebral protection during aortic arch repair, and systemic
      circulatory arrest during distal graft anastomosis. A total of 19 concomitant
      procedures were done in 17 patients. Mean selective cerebral perfusion time was
      78.1 +/- 16.5 minutes. RESULTS: Overall in-hospital mortality was 2% (95%
      confidence intervals, 0%-5.9%). On univariable analysis, permanent neurologic
      dysfunction was the only risk factor for in-hospital mortality. Postoperative
      temporary and permanent neurologic dysfunctions were 4% (95% confidence
      intervals, 0%-9.4%) and 4% (95% confidence intervals, 0%-9.4%), respectively. On
      univariable analysis, cardiopulmonary bypass time was the only risk factor for
      temporary neurologic dysfunction, and history of cerebrovascular disease was the
      only risk factor for permanent neurologic dysfunction. There was no significant
      correlation between selective cerebral perfusion time and temporary and permanent
      neurologic dysfunction. CONCLUSION: Integrated cerebral protective effect of
      antegrade selective cerebral perfusion and total arch replacement with an aortic
      arch branched graft could substantially reduce in-hospital mortality and
      postoperative neurologic dysfunction in patients with atherosclerotic arch
      aneurysms.

PMID- 11241085
TI  - Dynamic in vitro calcification of bioprosthetic porcine valves: evidence of
      apatite crystallization.
AB  - OBJECTIVE: Calcification is the most important cause of structural deterioration
      of glutaraldehyde-fixed bioprosthetic valves. Devitalization of tissue favors
      calcium deposits in the shape of apatite crystals. Host factors influence the
      extent and progression of calcification, but the phenomenon can also occur in
      vitro in the absence of a viable milieu. Whether calcific deposits obtained in
      vitro are similar to those found in vivo is unknown. METHODS: Four porcine frame
      mounted bioprostheses (St Jude Medical Bioimplant; St Jude Medical, Inc, St Paul,
      Minn) were tested in vitro by using a pulsatile accelerated calcification testing
      device at a frequency of 300 cycles per minute at 37 degrees C for 19 x 10(6)
      cycles with a rapid synthetic calcification solution (final product [calcium x
      phosphate], 130 mg/dL(2)). Three of the same type of xenografts explanted from
      human subjects because of calcific failure (time in place, 108 +/- 25.63 mo)
      served as control grafts. Each sample underwent gross and x-ray examination,
      histology, transmission and scanning electron microscopy, atomic absorption
      spectroscopy, electron microprobe analysis, and x-ray powder diffraction methods.
      RESULTS: All in vitro bioprostheses were heavily calcific, with intrinsic Von
      Kossa stain-positive deposits and a mean calcium content of 205.285 +/- 64.87
      mg/g dry weight. At transmission electron microscopy, nuclei of calcification
      involved mostly collagen fibers and interfibrillar spaces and, more rarely, cell
      debris and nuclei. Electron microprobe analysis showed a Ca/P atoms ratio of
      4.5:3, a value intermediate between hydroxyapatite and its precursor,
      octacalciumphosphate. X-ray powder diffraction showed a well-separated and sharp
      peak, which is typical of hydroxyapatite. Aggregates of plate-like crystals up to
      8 microm in size were observed at scanning electron microscopy, with a typical
      tabular hexagonal shape consistent with apatite. The morphologic and chemical
      findings in human explants were similar. CONCLUSIONS: Intrinsic calcification of
      glutaraldehyde-fixed porcine valves was induced in vitro. Electron microprobe
      analysis and x-ray powder diffraction findings were in keeping with apatite
      crystallization, such as that occurring in valve xenografts implanted in vivo.
      The model may be of value to accelerate the screening of anticalcific agents and
      may reduce the need for animal experiments.

PMID- 11241086
TI  - Adult cardiac myocytes survive and remain excitable during long-term culture on
      synthetic supports.
AB  - OBJECTIVE: Cardiomyocytes can be transplanted successfully into skeletal and
      cardiac muscle. Our goal was to determine the feasibility of grafting
      cardiomyocytes onto various synthetic supports to create an excitable and viable
      tissue for implantation. METHODS: Adult rat cardiomyocytes were cultured over an
      8-week period onto different substitutes, including human glutaraldehyde-treated
      pericardium (n = 3), equine glutaraldehyde-treated pericardium (n = 3),
      polytetrafluoroethylene (n = 8), Dacron polyester (n = 16), and Vicryl
      polyglactin (n = 8). RESULTS: Only the cells seeded on the Dacron survived, with
      the synthetic fibers colonized at 8 weeks. On the other supports, the number of
      myocytes progressively decreased from the first week, with their density (number
      of cells per square millimeter) being, after 20 days, 17 +/- 2 on the
      polytetrafluoroethylene and 5 +/- 1 on the human or equine pericardium compared
      with 45 +/- 3 on the Dacron. After 8 weeks of culture on Dacron, the sarcomeric
      protein (sarcomeric alpha-actinin) was detected in all cells. In addition, the
      staining was regularly arranged and well aligned in a striated pattern.
      Spontaneous beating activity was obtained. Moreover, electrical stimulation of
      the cell preparation resulted in the generation of calcium transients, the
      frequency of which followed the frequency of the electrical stimulation.
      CONCLUSIONS: These results suggest that adult cardiac myocytes remain viable and
      excitable during long-term culture on a 3-dimensional Dacron support, which might
      constitute a new synthetic cardiac tissue.

PMID- 11241087
TI  - Transplantation of the en bloc vascular system for coronary revascularization.
AB  - OBJECTIVES: Use of the free gastroepiploic artery graft for coronary
      revascularization has not been very popular because of its inclination toward
      vasospasm. We hypothesized that the cause of free gastroepiploic artery spasm was
      the graft damage caused by an interruption of venous drainage from the graft. To
      solve this problem, we developed a new method of free gastroepiploic artery
      grafting. METHODS: From January 1997 to October 1999, 33 patients underwent
      coronary artery bypass grafting with the free gastroepiploic artery according to
      our new method. The gastroepiploic artery graft was harvested en bloc with its
      satellite veins. The gastroepiploic vein was anastomosed to the right atrial
      appendage for venous drainage simultaneously with the gastroepiploic artery being
      grafted in the aortocoronary position. RESULTS: A total of 96 distal anastomoses
      were performed, including 33 free gastroepiploic artery grafts according to our
      method, 33 in situ left internal thoracic artery grafts, 26 saphenous vein
      grafts, and 4 radial artery grafts. Neither operative nor hospital death
      occurred. Early postoperative angiography revealed that all of the 33 free
      gastroepiploic artery grafts performed with our method were patent without spasm,
      and flow competition occurred only in 2 of those grafts. On late angiography, all
      15 free gastroepiploic artery grafts were patent without spasm. CONCLUSIONS: The
      free gastroepiploic artery grafting with venous drainage technique we developed
      can prevent graft spasm, leading to improved patency rate.

PMID- 11241088
TI  - Preoperative assessment of hand circulation by means of Doppler ultrasonography
      and the modified Allen test.
AB  - OBJECTIVE: The aims of this study were as follows: (1) to evaluate Doppler
      ultrasonography in assessing hand collateral circulation; (2) to define the
      criteria for an abnormal Doppler ultrasonography dynamic test result; and (3) to
      validate the modified Allen test. METHODS: The hand circulation of 71 patients
      scheduled for coronary artery bypass grafting was assessed by means of the Allen
      test and Doppler ultrasonography. The flow in the superficial palmar branch of
      the radial artery, the ulnar artery, and the dorsal digital thumb artery with and
      without radial artery compression were recorded. Flow patterns in the superficial
      palmar branch of the radial artery, the ulnar artery, and the dorsal digital
      thumb artery with radial artery compression were categorized into 4 groups: (1)
      no flow; (2) decreased flow; (3) reversed flow; and (4) increased flow. RESULTS:
      Among the 71 hands, 4 (5.6%) had an abnormal Allen test result (>10 seconds).
      Seven (10.6%) of 66 superficial palmar branches of the radial artery, 3 (4.2%) of
      71 ulnar arteries, and 2 (2.8%) of 71 dorsal digital thumb arteries showed no
      flow with radial artery compression, as measured by Doppler ultrasonography.
      There were significant differences among the 4 groups (superficial palmar branch
      of the radial artery: F = 7.0, P <.001; ulnar artery: F = 13.1, P <.001; and
      dorsal digital thumb artery: F = 8.4, P <.001) for the Allen test. Pairwise
      comparisons showed that when subjected to an Allen test, category 1 patients (no
      flow) had significantly longer recovery times compared with the other groups (P
      <.02 in all cases) for the superficial palmar branch of the radial artery, the
      ulnar artery, and the dorsal digital thumb artery. CONCLUSION: Absence of flow in
      the dorsal digital thumb artery with radial artery compression is considered an
      absolute contraindication to radial artery harvesting. An increased recovery time
      with the modified Allen test predicts absence of flow in the dorsal digital thumb
      artery in Doppler ultrasonographic flow patterns. This demonstrates the validity
      of the modified Allen test for primary screening.

PMID- 11241090
TI  - Percutaneous extracorporeal arteriovenous carbon dioxide removal improves
      survival in respiratory distress syndrome: a prospective randomized outcomes
      study in adult sheep.
AB  - OBJECTIVE: Arteriovenous carbon dioxide removal (AVCO(2)R) uses a simple
      arteriovenous shunt for CO(2) removal to minimize barotrauma/volutrauma from
      mechanical ventilation. We performed a prospective randomized outcomes study of
      AVCO(2)R in our new, clinically relevant model of respiratory distress syndrome.
      METHODS: Adult sheep (n = 18) received an LD(50) severe smoke inhalation and 40%
      third-degree burn. When respiratory distress syndrome developed (PaO (2)/FIO (2)
      < 200 at 40 to 48 hours), animals were randomized to the AVCO(2)R (n = 9) or sham
      group (n = 9) for 7 days. Ventilator management protocols mandated reductions in
      minute ventilation, first tidal volume to peak inspiratory pressure less than 30
      cm H(2)O, then respiratory rate when PaCO (2) was less than 40 mm Hg. PaO (2) was
      kept above 60 mm Hg by adjusting FIO (2). When FIO (2) was 0.21, animals were
      weaned. RESULTS: The study required 2946 animal-hours of critical care with 696
      AVCO(2)R hours. One died in each group during model development. AVCO(2)R flow
      from 820 mL/min to 970 mL/min (11% to 14% cardiac output) removed CO(2) at a rate
      of 92 to 116 mL/min (mean 103 mL/min; 93%-97% of CO(2) production). Heart rate,
      mean arterial pressure, cardiac output, and pulmonary arterial wedge pressure
      remained relatively constant. Within 48 hours, AVCO(2)R allowed significant
      ventilator reductions versus baseline in the following measurements: tidal volume
      (420 to 270 mL), peak inspiratory pressure (25 to 14 cm H(2)O), minute
      ventilation (13 to 5 L/min), respiratory rate (26 to 16 breaths/min), and FIO (2)
      (0.88 to 0.35). Ventilator-free days with AVCO(2)R were 3.9 versus 0.2 (P <.01)
      for sham animals, and ventilator-dependent days with AVCO(2)R were 2.4 versus 6.2
      (P <.01) for the 3 sham survivors. All 8 AVCO(2)R animals and 3 of 8 sham animals
      survived 7 days after randomization. CONCLUSIONS: Percutaneous AVCO(2)R achieved
      significant reduction in airway pressures, increased ventilator-free days,
      decreased ventilator-dependent days, and improved survival in a sheep model of
      respiratory distress syndrome.

PMID- 11241089
TI  - Heart transplantation in patients seventy years of age and older: A comparative
      analysis of outcome.
AB  - OBJECTIVE: Advanced age has traditionally been considered a contraindication for
      heart transplantation because of the reported adverse effect of increased age on
      long-term survival. However, as the field of transplantation continues to evolve,
      the criteria regarding the recipient's upper age limit have been expanded and
      older patients are being considered as potential candidates. We analyzed the
      outcome of heart transplantation in patients 70 years of age and older and
      compared these results with those in younger patients (<70 years) over a 4-year
      period. METHOD: We retrospectively analyzed the results of 15 patients 70 years
      of age and older who underwent heart transplantation between November 1994 and
      May 1999 and compared them with results in 98 younger patients undergoing
      transplantation during the same period RESULTS: The older age group had a higher
      preoperative left ventricular ejection fraction (P =.02), higher incidence of
      female donors (P =.02), and longer cardiac allograft ischemic time (P =.01). No
      differences were found regarding incidence of diabetes mellitus, donor age,
      donor/recipient weight ratio, and mismatch (<0.80). The 30-day or to-discharge
      operative mortality was similar in both groups (0% in the older vs 5.1% in
      younger patients). Actuarial survival at 1 year and 4 years was not statistically
      different between the older and younger patients (93.3% +/- 6.4% vs 88.3% +/-
      3.3% and 73.5% +/- 13.6% vs 69.1% +/- 5.8%, respectively). The length of
      intensive care unit stay and total post-transplantation hospital stay, incidence
      of rejection, and incidence of cytomegalovirus infection were similar between the
      groups. CONCLUSIONS: Heart transplantation in selected patients 70 years of age
      and older can be performed as successfully as in younger patients (<70 years of
      age) with similar morbidity, mortality, and intermediate-term survival. Advanced
      age as defined (> or =70 years) should not be an exclusion criterion for heart
      transplantation. The risks and benefits of transplant surgery should be applied
      individually in a selective fashion.

PMID- 11241091
TI  - Proximal aortic dissection with coronary malperfusion: presentation, management,
      and outcome.
AB  - BACKGROUND: Acute myocardial ischemia and infarction due to retrograde dissection
      of the aortic root reaching the coronary ostia is a potentially fatal condition.
      Surgical treatment of these patients relies on the re-establishment of an
      adequate coronary blood flow and on the rescue of jeopardized myocardium. This
      article reports the results of a selected group of 24 patients with type A acute
      aortic dissection and coronary artery dissection. We review our experience and
      illustrate our approach to this condition, which evolved over a 15-year period.
      METHODS: Between July 1985 and March 2000, 24 patients from a total of 211
      (11.3%) treated for acute type A aortic dissection had dissection of at least one
      of the coronary ostia. There were 14 men and 10 women. The mean age was 65.5
      years (median 61.7; range 41-78 years). The right coronary artery was involved in
      11 patients, the left in 4 patients, and both coronary arteries in 9 patients. At
      admission, 16 patients had Q waves (66%), inferior in 6 (25%) and anterior,
      lateral, septal, or posterior in 10 (41%). All procedures were done on an
      emergency basis within 10 hours (median 4 hours) after initial chest pain and
      within 2 hours after the patient's arrival. RESULTS: Hospital mortality was 20%
      (5 patients); 3 patients could not be weaned from cardiopulmonary bypass and died
      intraoperatively, and 2 patients died postoperatively of low cardiac output.
      CONCLUSIONS: As illustrated in this study, direct coronary repair is a safe
      alternative to bypass grafting. Aggressive myocardial resuscitation together with
      early operation is a key factor in the management of these patients.

PMID- 11241092
TI  - Methylprednisolone does not benefit patients undergoing coronary artery bypass
      grafting and early tracheal extubation.
AB  - OBJECTIVE: We sought to determine whether methylprednisolone, when administered
      to patients undergoing cardiac surgery, is able to ward off the detrimental
      hemodynamic and pulmonary alterations associated with cardiopulmonary bypass.
      METHODS: After institutional review board approval and informed consent was
      obtained, 90 patients scheduled for elective cardiac surgery were randomized to 1
      of 3 groups. Group 30MP patients received 30 mg/kg intravenous methylprednisolone
      during sternotomy and 30 mg/kg during initiation of cardiopulmonary bypass, group
      15MP patients received 15 mg/kg methylprednisolone at the same 2 times, and group
      NS patients received similar volumes of isotonic sodium chloride solution at the
      same 2 times. Perioperative care was standardized, and all caregivers were
      blinded to treatment group. Various hemodynamic and pulmonary measurements were
      obtained perioperatively, as well as fluid balance, weight, peak postoperative
      blood glucose level, and tracheal extubation time. RESULTS: Demographic and
      clinical characteristics of patients and intraoperative data were similar among
      the 3 groups. Patients receiving methylprednisolone (either dose) exhibited
      significantly increased cardiac index (P =.0006), significantly decreased
      systemic vascular resistance (P =.0005), and significantly increased shunt flow
      (P =.0020) during the immediate postoperative period. All 3 groups exhibited
      significant increases in alveolar-arterial oxygen gradient (P <.0001),
      significant decreases in dynamic lung compliance (P <.0001), and significant
      decreases in static lung compliance (P <.0001) during the immediate postoperative
      period, with no differences between groups. Perioperative fluid balance and
      weights were similar between groups. A statistically significant difference in
      peak postoperative blood glucose level existed (P =.016) among group NS (234 +/-
      96 mg/dL), group 15MP (292 +/- 93 mg/dL), and group 30MP (311 +/- 90 mg/dL). In
      patients extubated within 12 hours of intensive care unit arrival, a
      statistically significant difference in extubation times existed (P =.025)
      between group NS (5.7 +/- 2.3 hours), group 15MP (5.9 +/- 2.2 hours), and group
      30MP (7.5 +/- 2.7 hours). CONCLUSIONS: Methylprednisolone, as used in this
      investigation, offers no clinical benefits to patients undergoing elective
      coronary artery bypass grafting with cardiopulmonary bypass and may in fact be
      detrimental by initiating postoperative hyperglycemia and possibly hindering
      early postoperative tracheal extubation for undetermined reasons.

PMID- 11241094
TI  - Late thrombosis of the native aortic root after Norwood reconstruction for
      hypoplastic left heart syndrome.

PMID- 11241093
TI  - Experimental off-pump coronary artery revascularization with adenosine-enhanced
      reperfusion.
AB  - OBJECTIVE: Although beating heart coronary artery bypass grafting has recently
      gained popularity, it eliminates the protective strategies (ie, cardioplegia)
      developed for use in conventional cardiac operations. We recently introduced the
      technique of perfusion-assisted direct coronary artery bypass to perfuse the
      grafted vessels during multivessel off-pump coronary artery bypass grafting. In
      the present study we tested the hypothesis that intracoronary reperfusion with
      the cardioprotective agent adenosine during simulated perfusion-assisted direct
      coronary artery bypass attenuates reperfusion injury. METHODS: In anesthetized
      dogs the heart was exposed, and the left anterior descending coronary artery was
      ligated for 75 minutes. Reperfusion was achieved through a catheter in the left
      anterior descending coronary artery by means of a computer-controlled pump.
      Intracoronary left anterior descending coronary artery perfusion pressure was
      continuously matched to mean arterial blood pressure. In one group (adenosine
      group) 10 micromol/L adenosine was added to the blood during the first 30 minutes
      of reperfusion, whereas another group (vehicle group) received a comparable
      volume of saline solution. RESULTS: During the first 30 minutes of reperfusion,
      blood flow through the left anterior descending coronary artery was significantly
      greater (P <.05) in the adenosine group than in the vehicle group (150.6 +/- 21.9
      vs 50.2 +/- 11.3 mL/min at 15 minutes of reperfusion). Although there were no
      group differences in postischemic wall motion, infarct size was significantly
      smaller in the adenosine group than in the vehicle group (11.1% +/- 3.0% vs.
      28.0% +/- 4.0% of area at risk, P <.05). Myeloperoxidase activity in the necrotic
      tissue, an index of neutrophil accumulation, tended to be lower in the adenosine
      group than in the vehicle group (58.6 +/- 14.2 vs. 91.0 +/- 21.6 DeltaAbs Units x
      min(-1) x g(-1) tissue). In isolated postischemic left anterior descending
      coronary artery rings, the maximal relaxation response to the endothelium
      dependent vasodilator acetylcholine was significantly greater in the adenosine
      group than in the vehicle group (97.9% +/- 5.6% vs. 64.7% +/- 6.5%, P<.05).
      CONCLUSION: This novel reperfusion strategy for off-pump coronary artery bypass
      grafting can be used not only in cases requiring multiple grafting but also to
      attenuate necrosis and endothelial dysfunction in acute evolving infarction.

PMID- 11241095
TI  - Atrial pacing: an alternative treatment for protein-losing enteropathy after the
      Fontan operation.

PMID- 11241097
TI  - Aortic homograft interposition for management of complete tracheal anastomotic
      disruption after heart-lung transplantation.

PMID- 11241096
TI  - Monobloc aorto-mitral homograft as a treatment of complex cases of endocarditis.

PMID- 11241099
TI  - Myxoid leiomyosarcoma of the descending thoracic aorta.

PMID- 11241098
TI  - Minimal-access right atrial exposure for tumor extensions into the inferior vena
      cava.

PMID- 11241100
TI  - Mitral homografts for total tricuspid valve replacement: comparison of two
      techniques.

PMID- 11241101
TI  - Low-potassium dextran preservation solution improves lung function after human
      lung transplantation.

PMID- 11241102
TI  - pH-stat strategy and hypothermia of 25 degrees C alone should protect the central
      nervous system consistently from 75 minutes of circulatory arrest.

PMID- 11241104
TI  - Oxidative stress during cardiopulmonary bypass.

PMID- 11241105
TI  - Which cell does heat shock protein 72 induce?

PMID- 11241107
TI  - Aortic valve incompetence after implantation of Freestyle stentless
      bioprosthesis: a technical issue?

PMID- 11241109
TI  - Transmyocardial laser channeling, coronary artery bypass, statistical analyses,
      and their interpretations.

PMID- 11241112
TI  - Risk factors for rupture of abdominal aortic aneurysm based on three-dimensional
      study.
AB  - PURPOSE: Factors influencing the development or rupture of abdominal aortic
      aneurysms (AAAs) have not yet been confirmed. This study delineated the risk
      factors for rupture of AAAs as evaluated by means of a combination of three
      dimensional (3D) reconstruction and clinical data analysis. METHODS: The study
      population comprised Japanese patients in whom an atherosclerotic AAA had been
      diagnosed between January 1980 and December 1997. We obtained 3D-based data by
      means of computer-aided 3D reconstruction from computed tomography studies of
      AAAs. The data included the tortuosity of the aneurysm, maximum transverse
      diameter, length of the aneurysm, aneurysmal volume, aneurysmal surface area,
      largest aneurysmal cross-sectional area, ratio of transverse aneurysmal diameter
      to the length of the aneurysm (T/L), and amount of mural thrombus. Clinical data
      were collected from patient files. All data were assessed by means of
      multivariate analysis for their predictive value for expansion or rupture of AAA.
      RESULTS: The most efficient predictor of annual expansion rate of maximum
      transverse diameter (EX-D) was a combination of largest aneurysmal cross
      sectional area, tobacco use, and tortuosity. The most efficient predictor of
      annual expansion rate of aneurysmal volume (EX-V) was a combination of aneurysmal
      volume and blood urea nitrogen level. The most efficient predictors of aneurysmal
      rupture was a combination of EX-D, diastolic blood pressure, and T/L. CONCLUSION:
      Three-dimensional-based data on aneurysmal morphology, including T/L, largest
      aneurysmal crosssectional area, and aneurysmal volume, had strong predictive
      value for expansion and rupture of AAAs.

PMID- 11241111
TI  - The influence of surgical specialty training on the outcomes of elective
      abdominal aortic aneurysm surgery.
AB  - OBJECTIVE: The aim of this study was to determine the independent impact of
      surgeon speciality training (vascular, cardiac, or general surgery) on the 30-day
      risk-adjusted mortality rate after elective abdominal aortic aneurysm (AAA)
      surgery. PATIENTS AND METHODS: All patients undergoing elective AAA surgery in
      Ontario between April 1, 1992, and March 31, 1996, were included. A retrospective
      cohort study with linked administrative databases was undertaken. RESULTS: The
      average 30-day mortality rate was 4.1%. Of the 5878 cases studied, 4415 (75.1%)
      were performed by 63 vascular surgeons, 1193 (20.3%) by 53 general surgeons, and
      270 (4.6%) by 14 cardiac surgeons. After the adjustment for potential confounding
      factors of annual surgeon AAA volume, type of hospital, and patient age, sex,
      Charlson comorbidity score, and transfer status, the odds of patients dying were
      62% higher when the surgery was performed by a general surgeon than when it was
      performed by a vascular surgeon. Cardiac surgeons' patient outcomes were similar
      to those of vascular surgeons. CONCLUSIONS: Patients who undergo elective AAA
      repair that is performed by vascular or cardiac surgeons have significantly lower
      mortality rates than patients who have their aneurysms repaired by general
      surgeons. These results provide evidence that surgical specialty training in
      vascular procedures leads to better patient outcomes.

PMID- 11241113
TI  - A cohort study of coagulation parameters and the use of blood products in surgery
      of the thoracic and thoracoabdominal aorta.
AB  - OBJECTIVES: We sought to study the hemostatic profile and the use of blood
      products in patients undergoing thoracic and thoracoabdominal aortic aneurysm
      repair. METHODS: This is a cohort study comparing three groups of patients: 7
      undergoing elective acute normovolemic hemodilution (ANH); 15 undergoing elective
      procedures without ANH (non-ANH); and 8 undergoing repair of ruptured
      thoracoabdominal aneurysms. A control group of 10 patients was used for
      comparison of preoperative hemostasis. The parameters studied were platelet
      concentration, partial thromboplastin time (PTT), and international normalized
      ratio (before and after surgery), packed red blood cells, fresh frozen plasma,
      platelets, cryoprecipitates, donor exposure, and use of desmopressin and epsilon
      aminocaproic acid. Analysis of variance and multiple stepwise regression analysis
      were used. RESULTS: Before operation the patients with aneurysms had PTTs
      prolonged compared with control subjects (P <.05). After operation the ANH group
      had higher platelet counts than the ruptured group (P =.001) and higher platelet
      counts (P =.05) and lower PTTs (P =.001) than the non-ANH group. The ANH group
      was transfused fewer platelets than the non-ANH group (P =.001) and less of every
      blood product than the ruptured group (P =.05); statistically significant
      differences were not observed for packed red blood cells, fresh frozen plasma, or
      platelets. The ANH group was exposed to an average of 65 donors fewer than the
      ruptured group (P <.001) and 34 fewer than the non-ANH group (P <.05). These
      differences could not be explained by baseline coagulation status or by the
      intraoperative use of desmopressin or epsilon-aminocaproic acid. CONCLUSIONS: The
      coagulation abnormality identified before surgery is that of higher PTT values,
      suggesting a disturbance of the extrinsic coagulation pathway. Blood losses,
      donor exposure, and platelet use were highest in the ruptured group and lowest in
      the ANH group. After surgery the ruptured group exhibited the worst coagulation
      parameters, and the ANH group exhibited the best with higher platelet count and
      lower PTT values than the other groups. The ANH technique appears to be an useful
      adjunct in the anesthetic management of these patients.

PMID- 11241114
TI  - Laparoscopic aortoiliac surgery for aneurysm and occlusive disease: when should a
      minilaparotomy be performed?
AB  - PURPOSE: The purpose of this study was to determine the benefits and the
      indications of performing a minilaparotomy during laparoscopic abdominal
      aortoiliac reconstructions. METHODS: This prospective study was approved by the
      Commission Consultative de Protection des Personnes dans la Recherche Biomedicale
      of the University of Marseilles, and all patients gave their informed consent.
      Between January 1998 and March 2000, 27 patients (23 men; 4 women) with a mean
      age of 58.2 years (range, 42-76 years) underwent aortoaortic (n = 3),
      aortounifemoral (n = 4), or aortobifemoral (n = 20) bypass graft for aortoiliac
      occlusive disease (n = 20), emboligenic aortitis (n = 1), or abdominal aortic
      aneurysm (AAA) (n = 6). At the beginning of the trial, the decision was made to
      perform an intraoperative conversion to open surgery in case of bleeding (group
      0), when a totally laparoscopic procedure was possible (group I), or when a 6- to
      8-cm supraumbilical minilaparotomy was needed in case of technical difficulty
      (group II). In each case of AAA, the remaining lumbar arteries were controlled
      (group III); and for the last six patients of this series (group IV), a
      minilaparotomy was systematically performed. RESULTS: One patient was admitted
      with multiple organ failure and died on day 12 (3.7%) with a patent graft. One
      intraoperative conversion to open surgery (3.7%, group 0) was performed for
      bleeding; recovery was uneventful. Seven postoperative surgical procedures (26%)
      were necessary, including two cases of aortic bleeding because of hypertensive
      access. Seven procedures were totally laparoscopic (group I), and a
      minilaparotomy was performed in the other 19 cases, including seven cases of
      technical difficulty (group II). The mean operative and clamping times and the
      mean postoperative hospital stay were globally (P =.021) and individually (P < or
      =.016) significantly shorter in group IV when compared with those of the other
      three groups. Twenty patients (74%) had a postoperative hospital stay of 6 days
      or less (3-6 days), with minimal complaints of pain, tolerance of oral feeding on
      day 2, and mobilization on day 2 or 3. All bypass grafts remained patent after a
      mean follow-up of 11 months (1-26 months). CONCLUSION: With regard to the
      instrumentation presently available, this study shows the benefit of a
      minilaparotomy when performing a laparoscopic aortoaortic or aortofemoral bypass
      graft for the treatment of aortoiliac occlusive disease and AAA.

PMID- 11241115
TI  - Failure of exclusion of internal iliac artery aneurysms.
AB  - PURPOSE: We investigated in detail the state of internal iliac artery (IIA)
      aneurysms over the midterm after the exclusion procedure. METHODS: From January
      1990 to December 1998, 29 patients underwent the exclusion procedure for IIA
      aneurysms. The medical records of 27 survivors were retrospectively reviewed, and
      30 excluded aneurysms of these patients were followed up with computed tomography
      scanning over the midterm. RESULTS: In the immediate postoperative period, 26
      aneurysms were completely thrombosed, and four were incompletely thrombosed. In
      the midterm, 24 aneurysms were completely thrombosed (complete group), and six
      were incompletely thrombosed (incomplete group). No aneurysms expanded or
      ruptured during the follow-up period from 6 to 98 months (mean, 26 months). The
      size of the excluded aneurysm decreased in 22 of 24 aneurysms in the complete
      group, but no change in size was noted in the six aneurysms in the incomplete
      group. The preoperative size of the IIA aneurysm in the incomplete group was
      significantly larger than that in the complete group (P =.0047). The size of two
      aneurysms in the incomplete group was smaller than 3.0 cm. The aneurysms in the
      incomplete group extended significantly deep into the pelvis as compared with
      those in the complete group (P =.0008). CONCLUSIONS: The exclusion of IIA
      aneurysm did not reliably result in thrombosis of the aneurysm. For IIA aneurysms
      extending deeply into the pelvis, even if the size of the aneurysm is smaller
      than 3.0 cm, the exclusion procedure should not be performed.

PMID- 11241116
TI  - Eccentric stent graft compression: an indicator of insecure proximal fixation of
      aortic stent graft.
AB  - PURPOSE: The purpose of this study was to determine whether radiographically
      demonstrated proximal stent graft contour can be used as a marker for security of
      proximal neck fixation after endovascular aneurysm repair. METHODS: Stent graft
      structure was examined in 100 consecutive patients with abdominal aortic
      aneurysms who were treated with the stent graft. Stent graft integrity, stent
      contour, angulation, compression, and position were assessed by use of plain
      abdominal radiography, and the results were correlated with contrast computed
      tomography (CT) scanning, clinical findings, and outcomes. Repeated imaging was
      carried out during follow-up of 3 to 38 (mean, 12) months. RESULTS: Stent graft
      repair was successful in all 100 patients. No stent fractures were identified.
      Concentric compression of the proximal portion of the stent graft was visible in
      69% of patients and reflected deliberate oversizing of the stent graft at the
      time of implantation. In 5% of patients, a short eccentric compression deformity
      of the proximal stent was observed. This finding was associated with an increased
      risk of stent graft migration (P <.01) and with an increased risk for development
      of a late proximal (type I) endoleak (P <.01). Compared with CT scanning,
      abdominal radiography was less useful for assessment of short distances of
      migration (sensitivity 67%; specificity 79%). However, they provided better
      definition of the stent graft in relation to bony landmarks and better
      visualization of aortic calcification than CT with three-dimensional
      reconstruction. CONCLUSION: Plain abdominal radiographs are important in the
      postoperative evaluation of patients with aortic stent grafts. They allow for
      more precise evaluation of the structural elements of the stent graft than CT
      scanning and may disclose inadequate proximal fixation by demonstration of an
      eccentric compression deformity. They are less useful for assessment of
      migration.

PMID- 11241117
TI  - The role of magnetic resonance angiography for endoprosthetic design.
AB  - OBJECTIVES: Many patients with aortic aneurysms have renal insufficiency and may
      be at increased risk when conventional imaging modalities (contrast-enhanced
      computed tomography and arteriography) are used for aortic endograft design. Our
      objective was to determine if magnetic resonance angiography (MRA) could be used
      as the sole imaging modality for endoprosthetic design. METHODS: A total of 96
      consecutive patients who underwent endovascular repair of thoracic (5) and
      abdominal (91) aortic aneurysms (April 1998-December 1999) were included in this
      study. Data were collected prospectively. Gadolinium-enhanced MRA was used
      preoperatively in place of conventional imaging if renal insufficiency or a
      history of severe contrast reaction was present. The control group underwent
      conventional imaging. Endografts used included Ancure, AneuRx, and Talent.
      RESULTS: Fourteen patients (14.6%) had their endografts designed solely with MRA.
      Intraoperative access failure; proximal and distal extensions (unplanned);
      conversion to open, aborted procedures; and endoleaks occurred with equal
      frequency in both the MRA-designed and control groups (16.7% vs 18.3%,
      respectively; P =.33). Despite baseline renal insufficiency, there was no
      significant rise in the creatinine level after endograft implantation in patients
      with an MRA design (preoperative level, 1.8; postoperative level, 1.9; P =.5).
      CONCLUSION: MRA may be successfully used as the sole modality for aortic
      endograft design. The use of MRA for this purpose is noninvasive and minimizes
      nephrotoxic risk.

PMID- 11241118
TI  - Reoperations for carotid artery stenosis: role of primary and secondary
      reconstructions.
AB  - PURPOSE: This is an analysis of the role of primary and secondary carotid artery
      reconstructions and systemic risk factors on the incidence and timing of
      reoperations and their perioperative and late outcomes. METHODS: This is a
      retrospective analysis of prospectively stored data. Between 1981 and 1999, 69
      secondary carotid artery procedures were performed on 66 patients (3 were
      bilateral). Of these, 29 operations and patients came from my series of 1514
      primary carotid endarterectomies (CEAs). Overall, secondary operations were
      performed on 37 women (1 bilateral) and 29 men (2 bilateral) with a mean age of
      68 years. Indications for reoperation were transient ischemic attack in 27%,
      stroke in 12%, global ischemia in 9%, and asymptomatic > or = 70% recurrent
      stenosis in 52%. Secondary reconstruction was by saphenous vein patching in 57%
      (n = 39), Dacron patching in 29% (n = 20), polytetrafluoroethylene patch in 1% (n
      = 1), and interposition bypass graft in 13% (n = 9). The main outcome measures
      included restenosis, re-restenosis, and perioperative and late stroke and death.
      RESULTS: Reoperations were more frequent after originally primarily closed CEA
      (6.2%) than after patched CEA (1.6%, P =.01). Reoperations after Dacron-patched
      CEA occurred at a mean of 16 months compared with a mean of 84 months for vein
      patched CEA (P <.001). Male sex and history of smoking have a slightly adverse
      but not statistically significant effect on the incidence and time of
      reoperation. Restenosis in the distal common carotid artery requiring reoperation
      had a near-linear rate of occurrence, whereas that in the internal carotid artery
      segment was bimodal with a higher incidence in the first 3 years and after 7
      years. There were no (0%) 30-day perioperative deaths. There were two (2.9%) 30
      day strokes (1 major, 1 minor). Over a mean follow-up of 50 months (range, 1
      180), the Kaplan-Meier cumulative survival was 74% at 5 years and 54% at 10
      years. This is significantly higher than late death after primary CEA independent
      of age. The cumulative freedom from stroke rate was 90% at 5 years and 86% at 10
      years. After secondary procedures re-recurrent stenosis > or = 25% occurred in
      25% (n = 17), > or = 50% in 13% (n = 9), and > or = 70% in 4% (n = 3). There was
      no statistically significant difference in stroke or re-restenosis rates between
      vein-patched, Dacron-patched, and bypassed reoperations, although re-recurrence
      tended to occur earlier after Dacron-patched than vein-patched procedures.
      Analysis of pooled literature data and the results of this study for stroke and
      re-restenosis outcomes by type secondary reconstruction (patch versus bypass
      graft) and by material (vein versus synthetic) give a balanced picture of near
      equality for each. Vein- and Dacron-patched arteries have similar outcomes,
      whereas polytetrafluoroethylene appears to be superior to vein and Dacron for
      interposition bypass graft. CONCLUSIONS: Secondary carotid artery operations are
      more frequent after primarily closed CEA than patched CEA. Perioperative
      mortality and stroke rates for reoperations are within the acceptable window of
      primary CEA. The incidence of late death after reoperations is higher than after
      primary CEA. The perioperative stroke, late stroke, and re-restenosis outcomes of
      vein- and Dacron-patched secondary operations are similar, as are those for
      patched and bypassed carotid arteries.

PMID- 11241119
TI  - Efficacy of a proximal occlusion catheter with reversal of flow in the prevention
      of embolic events during carotid artery stenting: an experimental analysis.
AB  - OBJECTIVE: The role of percutaneous angioplasty and stenting of carotid
      bifurcation lesions has been limited by its potential for producing embolic
      debris. We evaluated the efficacy of a proximal occlusion catheter (POC) in the
      prevention of embolic events during carotid artery stenting. In addition,
      pressure measurements relevant to the clinical application of this device were
      obtained from 10 patients undergoing carotid endarterectomy. METHODS: The POC is
      a guiding catheter with an occlusion balloon attached on the outside of the
      catheter at its distal end. Occlusion of the common carotid artery (CCA) was
      achieved by inflating the balloon while access to carotid bifurcation lesions was
      obtained through the inner lumen. The POC was inserted in the CCA of 10 dogs via
      the femoral artery. The side port of the POC was connected to a sheath placed in
      the femoral vein, thereby creating an external arteriovenous shunt. Ten
      artificial radiopaque particles simulating embolic particles and contrast agent
      were introduced in the CCA and monitored fluoroscopically. As a control, the same
      procedure was performed with a standard guiding catheter without an occlusion
      balloon. In 10 patients undergoing carotid endarterectomy, the internal carotid
      artery (ICA) and external carotid artery stump pressures and the pressure in the
      internal jugular vein were measured. RESULTS: Without the external arteriovenous
      shunt, in all animals there was prograde flow in the distal CCA despite CCA
      occlusion. This flow was derived from the thyroid artery. However, once the
      arteriovenous shunt was activated, reversal of flow in the distal CCA was
      achieved in each animal, and all the artificial particles were recovered from the
      side port of the POC. In the control group, each particle embolized to the brain
      (100%, P <.01). In the patients, the mean stump pressures in the ICA and external
      carotid artery and the jugular vein pressure were 51.8 +/- 14.2, 62.2 +/- 15.1,
      and 6.5 +/- 3.5 mm Hg, respectively. In each case, the jugular vein pressure was
      the lowest among the three. CONCLUSIONS: Obtaining proximal CCA control by
      inflating the POC does not sufficiently prevent embolization. However, reversal
      of flow in the ICA can always be created with the external shunt, which
      effectively prevents embolization. Thus, POC may markedly lower procedural stroke
      rates during carotid artery stenting. The ability of POC to prevent embolization
      before crossing the lesion with a guidewire may be an important advantage over
      other distal protection devices.

PMID- 11241120
TI  - Recurrent thromboembolism in patients with vena cava filters.
AB  - BACKGROUND: Patients with venous thromboembolic disease are treated with
      anticoagulation or vena cava filter placement to prevent pulmonary embolism. A
      recent report suggested that filter placement may increase the risk of recurrent
      deep venous thrombosis (DVT) and prompted a review of our experience. METHODS:
      Prospectively collected data on 2109 consecutive patients receiving filters were
      evaluated for recurrent thromboembolism, vena cava occlusion, or venous stasis
      ulceration. Outcomes were stratified and analyzed according to the use of
      anticoagulants at the time of insertion and at follow-up. Incidence rates were
      also compared with reports in the literature. RESULTS: Of 1191 patients with DVT
      at filter placement, complete follow-up data at a mean of 9 years were available
      for 465. Recurrent DVT was found in 12% of the 241 patients who were given
      anticoagulants and 15% of the 224 who were not (P >.05). We also failed to find a
      significant association between the use of anticoagulation and the incidence of
      pulmonary embolism (2%), stasis ulceration (2%), and vena cava occlusion (0.0).
      CONCLUSIONS: Recurrent DVT in patients with existing thromboembolic disease is
      not an unexpected event, which, in our experience, is not associated with
      anticoagulant or filter use. Anticoagulation should be used when possible to
      treat existing DVT to reduce thrombus progression and potentially to reduce
      subsequent complications but does not seem to reduce the rate of recurrent DVT.
      Rates of recurrent thromboembolism were consistently less than the 20% to 50%
      reported in the literature.

PMID- 11241121
TI  - Systematic study of occult pulmonary thromboembolism in patients with deep venous
      thrombosis.
AB  - PURPOSE: This study was carried out to evaluate the prevalence and extension of
      pulmonary thromboembolism (PTE) in symptom-free patients with symptomatic deep
      venous thrombosis (DVT) of lower limbs and to evaluate their possible implication
      in the adequate treatment of thromboembolic disease. MATERIALS AND METHODS: We
      prospectively studied, using noninvasive examination (pulmonary spiral computed
      tomography [CT] angiography), 159 consecutive patients with acute DVT confirmed
      by duplex scanning without symptoms of PTE. CT was repeated at 30 days to study
      evolution of these clinically occult PTE. RESULTS: We observed silent PTE in 65
      patients (41%) in all levels of lower limb venous thrombosis. Prevalence of PTE
      showed significant association with male sex (P =.001) and previously diagnosed
      heart disease (P =.023). There was no significant association between the level
      of DVT and the presence of PTE nor the DVT side and thromboembolic pulmonary
      localization. Of the 65 patients with positive CT exploration results for PTE, 52
      had characteristics of acute PTE, 10 had chronic PTE, and 3 patients had both.
      Chronic PTE was found more frequently in patients with previous episodes of DVT
      (P =.024). A total of 165 pulmonary artery-affected segments were found at
      several locations: 5 main, 35 lobar, 58 interlobar, and 67 segmental. Multiple
      segments were affected in 59% of patients. Repeat CT examinations were performed
      at 30 days in 53 of 65 patients with positive CT scanning results. In 48 cases
      (90.6%) PTE had completely disappeared. CONCLUSIONS: Silent PTE occurred
      frequently in association with clots of lower limbs. The CT scan had a good
      availability and cost-effectiveness to detect clinically underestimated PTE. The
      incorporation of this exploration in the systematic diagnostic strategy of most
      patients with DVT to establish the extension of thromboembolic disease at
      diagnosis may be useful in the evaluation of added pulmonary artery symptoms and
      treatment strategies.

PMID- 11241123
TI  - Long-term assessment of cryopreserved vein bypass grafting success.
AB  - PURPOSE: When autogenous vein is unavailable, cryopreserved veins have been used
      in patients as a means of attempted limb salvage. We evaluated the long-term
      patency and limb salvage rates for patients undergoing bypass grafting with
      cryopreserved veins. METHODS: Medical records were reviewed for patients
      undergoing cryovein bypass grafting at two hospitals from 1992 to 1997. Follow-up
      data were obtained from subsequent admissions and office records. Primary
      outcomes were death, amputation, and primary patency. Skin integrity and
      additional bypass grafting procedures were assessed when data were available.
      Analysis was performed by means of life-table and chi(2) analyses with the
      Statistical Package for Social Sciences (SPSS). RESULTS: Seventy-six patients
      (mean age, 70 +/- 11 years) underwent 80 procedures. Indications for surgery were
      tissue loss (63%), rest pain (24%), acute ischemia (11%), and other (2%). Early
      complications included 3 deaths (4%), 14 acute thromboses (18%), and 7 major
      amputations (9%). The mean follow-up period was 17.8 +/- 20.89 months (range, 0
      77 months). The primary patency rate was determined to be 36.8% at 1 year and
      23.6% at 3 years by means of life-table analysis. The limb salvage rate was 65.5%
      at 1 year and 62.3% at 3 years. Skin integrity was found to be compromised in 17
      (55%) of 31 patients who were available to follow-up. Nine patients (11.3%)
      underwent additional ipsilateral revascularization or revisions, with one of
      three of these patients eventually requiring a major amputation. CONCLUSION:
      Cryopreserved vein may be a reasonable alternative conduit for limb salvage when
      no autogenous tissue is available; it has an acceptable limb salvage rate (62.3%)
      at 3 years. Long-term patency remains relatively poor, with only 23.6% of
      originally placed grafts patent at 3 years. The use of cryopreserved veins should
      be strictly confined to limb salvage after a thorough search for autogenous
      tissue has been exhausted.

PMID- 11241122
TI  - Optimal oral anticoagulant intensity to prevent secondary ischemic and
      hemorrhagic events in patients after infrainguinal bypass graft surgery. Dutch
      BOA Study Group.
AB  - OBJECTIVES: The purpose of this study was to determine the optimal intensity of
      oral anticoagulation in patients who participated in a randomized trial of oral
      anticoagulants or aspirin after infrainguinal bypass graft surgery. METHODS: The
      distribution of patient-time spent in international normalized ratio (INR)
      classes of 0.5 INR unit was calculated assuming a linear change between
      successive measurements. INR-specific incidence rates of ischemic and hemorrhagic
      events were calculated as the ratio of the number of events at a certain INR
      category and the total patient-time spent in that class. The relationship between
      INR class and event rates was quantified by rate ratios calculated in a Poisson
      regression model. RESULTS: In 1326 patients (mean age, 69 years) 41,928 INR
      measurements were recorded in 1698 patient-years. Patients spent 50% of the total
      time within the target range of 3.0 to 4.5 INR. Most of the patient-time (60%)
      was spent between 2.5 and 3.5 INR. For each increasing class of 0.5 INR, the
      incidence of ischemic events (n = 154, INR data on event available in 49%)
      decreased by a factor of 0.97 (95% CI, 0.87-1.08). The incidence of major
      bleeding (n = 123, INR data on event available in 65%) increased significantly by
      a factor of 1.27 (95% CI, 1.19-1.34) for each increasing 0.5 INR category. The
      optimal target range was 3.0 to 4.0 INR, with an incidence of 3.8 events (0.9
      ischemic and 2.9 hemorrhagic) per 100 patient-years. CONCLUSIONS: The target
      range of 3.0 to 4.0 INR is the optimal range of achieved anticoagulation
      intensity and is safe for the prevention of ischemic events in patients after
      infrainguinal bypass graft surgery.

PMID- 11241124
TI  - Heparin-bonded Dacron or polytetrafluoroethylene for femoropopliteal bypass
      grafting: a multicenter trial.
AB  - BACKGROUND: Dacron (polyester fiber) was largely abandoned for femoropopliteal
      bypass grafts 30 years ago because saphenous vein achieved better patencies.
      However, in patients taking aspirin, patency in above-knee femoropopliteal bypass
      grafts has recently been shown to be equivalent to that with saphenous vein. We
      compared heparin-bonded Dacron (HBD) and polytetrafluoroethylene (PTFE) in a
      randomized multicenter trial including below-knee popliteal or tibioperoneal
      trunk bypass graft where the long saphenous vein was absent or inadequate.
      METHODS: Over 28 months, 209 patients undergoing femoropopliteal bypass grafts
      (180 above-knee, 29 below-knee) were randomized to HBD (n = 106) or PTFE (n =
      103). Each patient was given aspirin (300 mg/d) before surgery, and this
      continued unless the patient had intolerance to the aspirin. RESULTS: The mean
      follow-up was 42 months (range, 28-55). Fifteen (7.1%) patients died with patent
      grafts, and three (1.4%) infected grafts were removed. Patency (measured with
      Kaplan-Meier survival analysis) at 1, 2, and 3 years for HBD was 70%, 63%, and
      55% compared with 56%, 46%, and 42%, respectively, for PTFE (P =.044). A total of
      67 secondary interventions were performed on 48 thrombosed grafts; long-term
      patency was achieved in only three. Risk factors for arterial disease did not
      significantly influence patency. Amputations have been performed in 23 patients,
      six after HBD and 17 after PTFE bypass grafts (P =.015). CONCLUSIONS: HBD
      achieved better patency than PTFE, which carried a high risk of subsequent
      amputation.

PMID- 11241125
TI  - Interobserver variability in aortoiliac and femoropopliteal duplex scanning.
AB  - PURPOSE: The interobserver variability of aortoiliac and femoropopliteal duplex
      scanning in peripheral arterial occlusive disease was assessed. METHODS: Two
      experienced, independent vascular technologists investigated in random order 61
      consecutive patients sent to the vascular laboratory for investigation of the
      aortoiliac or femoropopliteal arteries. In each aortoiliac vessel segment, the
      proximal, mid, and distal peak systolic velocities (PSVs) were measured, and
      corresponding PSV ratios were calculated. The superficial femoral artery was
      divided in 10-cm segments with a roll-centimeter taped from the upper patella
      margin. Interclass correlation coefficients (ICCs) were calculated as a means of
      appreciating the measurement variability of the PSV ratio values as a continuous
      variable and the Kappa value for the PSV ratio categories of less than 2.0, 2.0
      through 3.0, more than 3.0, and occlusions. RESULTS: The overall ICC and Kappa
      values were 0.72 (95% CI, 0.63-0.79) and 0.53 for the aortoiliac tract and 0.85
      (95% CI, 0.79-0.89) and 0.73 for the femoropopliteal tract. Agreement in the PSV
      ratio categories was 85% in the aortoiliac and 87% in the femoropopliteal tract.
      Interobserver variation increased markedly with increasing PSV ratio. In the PSV
      ratio category between 2.0 to 3.0, indicating a borderline stenosis, a
      substantial disagreement was found (aortoiliac, 1 of 8 agreement;
      femoropopliteal, 2 of 8 agreement). CONCLUSION: A moderate interobserver
      agreement was found in the duplex investigation of the aortoiliac and
      femoropopliteal arteries. One should be aware of this in clinical decision
      making, especially in cases of borderline stenoses. In these cases, repetition of
      the measurement or additional diagnostics is advocated.

PMID- 11241126
TI  - Transfer function index of pulse volume recordings: a new method for vein graft
      surveillance.
AB  - OBJECTIVE: Color flow duplex scanning is currently the best method available for
      vein graft surveillance. However, it puts a considerable strain on the workload
      of a vascular unit and requires a highly trained operator. The aim of this study
      was to develop and validate a new, noninvasive tool for graft surveillance. The
      utility of transfer function index (TFI) of pulse volume recordings is tested for
      this purpose. METHODS: The design of the study was a blind comparative study that
      involved 70 testing procedures that were performed on 58 different infrainguinal
      vein bypass grafts. The TFI was measured with a portable vascular laboratory
      multi-cuff unit. Ankle/brachial indexes were obtained with the same device. Color
      flow duplex scanning was used as a diagnostic standard. A graft was defined as at
      risk, according to duplex scanning, if a local stenosis with a V2/V1 more than 2
      was found or if peak systolic velocity remained less than 45 cm/s throughout the
      graft. The repeatability of the method was tested on 30 grafts. RESULTS: A total
      of 63 tests were available for analysis. Seven tests were excluded. Four were
      excluded because they had unreliable TFI measurement due to cardiac arrhythmias,
      and in three tests, the whole graft could not be visualized in the duplex scan.
      Forty normal and 22 at-risk grafts were found. One graft was occluded. The TFI
      was significantly lower for at-risk grafts (0.89) versus normal grafts (1.09; P
      =.005). A TFI of 1.02 or less correctly detected 21 of 22 at-risk grafts. The
      sensitivity, specificity, and accuracy were 96%, 65%, and 76%, respectively. The
      ability of the ankle/brachial index to detect the at-risk grafts was clearly
      inferior to the TFI. The repeatability of the method at proximal thigh, distal
      thigh, and proximal calf was +/- 0.21, +/- 0.07, and +/- 0.14, respectively.
      CONCLUSION: The TFI is a sensitive and reliable method to detect an at-risk
      graft. The examination is noninvasive, simple, quick to perform, and well
      tolerated by the patients. We suggest that the TFI could be the first-line
      screening method in vein graft surveillance.

PMID- 11241127
TI  - Construction and biological characterization of an HB-GAM/FGF-1 chimera for
      vascular tissue engineering.
AB  - OBJECTIVE: Cardiovascular tissue engineering approaches to vessel wall
      restoration have focused on the potent but relatively nonspecific and heparin
      dependent mesenchymal cell mitogen fibroblast growth factor 1 (FGF-1). We
      hypothesized that linking FGF-1 to a sequence likely to bind to cell surface
      receptors relatively more abundant on endothelial cells (ECs) might induce a
      relative greater EC bioavailability of the FGF-1. We constructed a heparin
      binding growth-associated molecule (HB-GAM)/FGF-1 chimera by linking full-length
      human HB-GAM to the amino-terminus of human FGF-1beta (21-154) and tested its
      activities on smooth muscle cells (SMCs) and ECs. METHODS: Primary canine carotid
      SMCs and jugular vein ECs were plated in 96-well plates in media containing 10%
      fetal bovine serum and grown to approximately 80% confluence. After being growth
      arrested in serum-free media for 24 hours, the cells were exposed to
      concentration ranges of cytokines and heparin, and proliferation was measured
      with tritiated-thymidine incorporation. Twenty percent fetal bovine serum was
      used as positive control, and phosphate-buffered saline was used as negative
      control. RESULTS: In the presence of heparin the HB-GAM/FGF-1 chimera stimulated
      less SMC proliferation than did the wild-type FGF-1 with a median effective dose
      of approximately 0.3 nmol versus approximately 0.1 nmol (P <.001). By contrast,
      the chimera retained full stimulating activity on EC proliferation with a median
      effective dose of 0.06 nmol for both cytokines. Unlike the wild-type protein, the
      chimera possessed heparin-independent activity. In the absence of heparin, the
      chimera induced dose-dependent EC and SMC proliferation at 0.06 nmol or more
      compared with the wild-type FGF-1, which stimulated minimal DNA synthesis at 6.0
      nmol concentrations. CONCLUSIONS: The HB-GAM/FGF-1 chimera displays significantly
      greater and uniquely heparin-independent mitogenic activity for both cell types,
      and in the presence of heparin it displays a significantly greater EC
      specificity.

PMID- 11241128
TI  - Vein adaptation to arterialization in an experimental model.
AB  - PURPOSE: The events preceding myointimal thickening in vein grafts after vascular
      reconstructions are not well characterized. Indeed, the injury response
      associated with vein graft arterialization may be different than that observed in
      the balloon angioplasty model. Therefore, we used a rat model to study the early
      cellular response after arterialization of vein grafts. METHODS: Epigastric veins
      were placed as femoral artery interposition grafts in 37 male Lewis rats (weight
      range, 350-400 g). Vein grafts and contralateral epigastric veins were harvested
      at different time points (6 hours, 1 day, 2 days, 3 days, 7 days, 14 days, 21
      days, 30 days, and 70 days). Tissue specimens were processed for histology and
      immunohistochemistry with antibodies for the proliferating cell nuclear antigen
      (PCNA) and for different cell types. Terminal deoxynucleotidyl transferase
      mediated dUTP-biotin nick end labeling (TUNEL) assay was used as a means of
      determining the presence of apoptosis. Electron microscopy was used as means of
      assessing the integrity of the endothelial cell surface (SEM) and confirming the
      presence of apoptosis (TEM). Specimens were also snap frozen in liquid nitrogen
      for RNA isolation and molecular analysis. RESULTS: At 1 day, endothelial
      denudation with platelet deposition on the surface was shown by means of SEM.
      Both apoptosis and necrosis of smooth muscle cells (SMCs) were present in the
      media, along with monocyte infiltration. Cellular proliferation and apoptosis
      were most intense within the first week of implantation. PCNA staining was first
      seen in the adventitial fibroblasts and microvessels, then in the medial SMCs at
      3 days. With reverse transcriptase polymerase chain reaction, upregulation of
      vascular endothelial growth factor (VEGF) messenger RNA (mRNA) was noted at 1
      day. Myointimal thickening progressively developed, with no apparent diminution
      of the luminal area as long as 70 days after implantation. By means of the
      analysis of the transforming growth factor beta1, mRNA showed expression during
      intimal thickening and accumulation of extracellular matrix. Reendothelialization
      was complete at 30 days. CONCLUSIONS: These observations indicate that the
      cellular composition in our vein graft model is similar to human stenotic
      explants. Endothelial denudation is observed in rat vein grafts with complete
      regeneration by 30 days. VEGF mRNA is upregulated at 1 day, followed by
      proliferation of microvessel endothelial cells in the adventitia. Cellular
      proliferation and apoptosis are minimal after 21 days, with progressive intimal
      thickening likely to be the result of matrix accumulation.

PMID- 11241129
TI  - Molecular mechanisms of aortic wall remodeling in response to hypertension.
AB  - OBJECTIVE: The molecular basis of vascular response to hypertension is largely
      unknown. Both cellular and extracellular components are critical. In the current
      study we tested the hypothesis that there is a balance between vascular cell
      proliferation and cell death during vessel remodeling in response to
      hypertension. METHODS: A midthoracic aortic coarctation was created in rats to
      induce an elevation of blood pressure proximal to the coarctation. The time
      course was 1 and 3 days and 1, 2, and 4 weeks for the study of the proximal
      aorta. Ribonuclease protection assay and Western blot analysis were used to
      evaluate gene expression of growth and apoptosis-related cytokines with two sets
      of multiple probes, rCK-3 and rAPO-1. Cell proliferation was determined with BrdU
      (5-bromo-2'-deoxyuridine) incorporation. Apoptosis was examined with TUNEL
      (transferase-mediated dUTP nick end-labeling). Morphometry was performed on
      histologic sections. RESULTS: Coarctation produced hypertension in the proximal
      aorta, 118 +/- 9 mm Hg versus 94 +/- 6 mm Hg in controls (P <.002). Both
      messenger RNA and protein levels of transforming growth factor (TGF)-beta1 and
      TGF-beta3 were increased (P <.005 vs controls). Messenger RNA and protein of Bcl
      xS and Fas ligand, known as proapoptotic factors, were both reduced after
      coarctation (P <.005 vs controls). There was increased BrdU incorporation at 3
      days and 1 and 2 weeks (P <.001 vs controls). There were no remarkable changes in
      the apoptosis rate until 4 weeks later. CONCLUSION: Cell proliferation was
      stimulated at 3 days, and apoptosis was halted until 4 weeks. These changes were
      associated with upregulation of TGF-beta and downregulation of Bcl-xS and Fas
      ligand gene expression. These findings suggest that a coordinated regulation of
      cell proliferation and cell death contributes to arterial remodeling in response
      to acute sustained elevation of blood pressure. Cell proliferation precedes
      apoptosis by 2 weeks in this procedure.

PMID- 11241130
TI  - Inhibition of inducible nitric oxide synthase limits nitric oxide production and
      experimental aneurysm expansion.
AB  - PURPOSE: Nitric oxide (NO), frequently cited for its protective role, can also
      generate toxic metabolites known to degrade elastin. Both abdominal aortic
      aneurysms (AAAs) and inducible nitric oxide synthase (iNOS) are associated with
      inflammatory states, yet the relationship between NO production by iNOS and AAA
      development is unknown. The current study examines iNOS expression, NO
      production, and the effects of selective inhibition of iNOS by aminoguanidine in
      experimental AAA. METHODS: An intra-aortic elastase infusion model was used.
      Control rats received intra-aortic saline infusion and postoperative
      intraperitoneal saline injections (Group 1). In the remaining groups, intra
      aortic elastase infusion was used to induce aneurysm formation. These rats were
      treated with intraperitoneal injections of saline postoperatively (Group 2),
      aminoguanidine postoperatively (Group 3), or aminoguanidine preoperatively and
      postoperatively (Group 4). Aortic diameter and plasma nitrite/nitrate levels were
      measured on the day of surgery and postoperative day 7. Aortas were harvested for
      biochemical and histologic analysis on postoperative day 7. RESULTS: Infusion of
      elastase produced AAAs (P <.001) with significant production of iNOS (P <.05) and
      nitrite/nitrate (P <.003) compared with controls. Selective inhibition of iNOS
      with aminoguanidine in elastase-infused aortas significantly reduced aneurysm
      size (P <.01) compared with elastase infusion alone. Aminoguanidine-treated rats
      displayed suppression of iNOS expression and plasma nitrite/nitrate production
      not significantly different from the control group. Histologic evaluation
      revealed equivalent inflammatory infiltrates in elastase-infused groups.
      CONCLUSION: Expression of iNOS is induced and plasma nitrite/nitrate levels are
      increased in experimental AAA. Inhibition of iNOS limits NO production and iNOS
      expression, resulting in smaller aneurysm size. NO production by iNOS plays an
      important role with detrimental effects during experimental aneurysm development.

PMID- 11241131
TI  - Heparin modulates integrin function in human platelets.
AB  - PURPOSE: Heparin binds to human platelets and can cause activation and
      aggregation, although the mechanisms are unknown. To determine how heparin alters
      platelet function, we identified platelet-binding sites for heparin and measured
      heparin's influence on the function of platelet integrin alpha(IIb)beta(3)
      (glycoprotein IIb/IIIa). METHODS: Photoaffinity cross-linking and affinity
      chromatography experiments were performed to identify platelet membrane proteins
      that bind heparin. Heparin's effect on fibrinogen binding to platelets was
      measured with a radioligand-binding assay. The translocation to the cytoskeleton
      of Rap2, a guanosine triphosphate-binding protein, was measured from platelets
      aggregating in response to heparin and other agonists. RESULTS: Cross-linking and
      affinity chromatographic experiments positively identified the integrin
      alpha(IIb)beta(3) as a heparin-binding site. Heparin aggregation was calcium
      dependent. Low concentrations of unfractionated porcine mucosal heparin (2-5
      U/mL) significantly increased fibrinogen I 125 binding to activated platelets,
      whereas higher doses did not. Heparin-mediated platelet aggregation was
      completely blocked by GRGDS peptide (5 mmol/L), a competitive inhibitor of
      fibrinogen binding, and was blocked by EDTA (2 mmol/L), which dissociates the
      functional integrin complex. Aggregation was associated with Rap2 translocation
      to the cytoskeleton, a sign of outside-in signaling. CONCLUSIONS: Heparin binds
      to the alpha(IIb)beta(3) integrin in vitro and ex vivo, and heparin increases
      fibrinogen binding to the integrin. Heparin-mediated aggregation requires an
      intact integrin and ligand and leads to Rap2 translocation to the cytoskeleton-an
      outside-in signal of ligand engagement. Heparin may directly modulate platelet
      integrin function, most likely through direct binding and modulation of integrin
      function.

PMID- 11241132
TI  - The C-terminal domain of thrombospondin-1 induces vascular smooth muscle cell
      chemotaxis.
AB  - OBJECTIVE: Thrombospondin-1 (TSP-1), an acute-phase reactant implicated in
      vascular disease, is a 420-kd multifunctional glycoprotein chemotactic for
      vascular smooth muscle cells (VSMCs). TSP-1 has six domains of repeating
      homologous amino acid sequences: N-terminal, procollagen homology, type 1 repeat,
      type 2 repeat, type 3 repeat/RGD (T3), and C-terminal (COOH). The purpose of this
      experiment was to determine which domains of TSP-1 induce VSMC chemotaxis.
      METHODS: A modified Boyden Chamber chemotaxis assay was used to assess VSMC
      migration. Serum-free medium, TSP-1, or each of the fusion proteins (10 and 20
      microg/mL) synthesized for the different domains were placed in the bottom wells.
      Quiescent bovine aortic VSMCs (50,000) were placed in the top wells. After 4
      hours at 37 degrees C, migrated VSMCs were recorded as cells per five fields
      (400x) and analyzed with the paired t test. To verify the fusion protein data, we
      performed chemotaxis assays with antibodies to each of the domains (25 microg/mL)
      combined with TSP-1 (20 microg/mL) in the bottom wells and VSMCs in the top
      wells. RESULTS: The COOH domain significantly stimulated VSMC chemotaxis (P =
      <.001). To a lesser extent, the N-terminal and T3 domains also induced chemotaxis
      (P <.05). However, only the anti-COOH antibody (C6.7) and the anti-integrin
      associated protein portion of COOH antibody (D4.6) significantly inhibited TSP-1
      induced VSMC chemotaxis (by 85% and 92%, respectively). CONCLUSIONS: These
      results implicate the COOH domain as the portion of the TSP-1 molecule primarily
      responsible for VSMC chemotaxis. This experiment suggests that future strategies
      in the prevention of VSMC migration, an initial step in the development of
      vascular lesions, may involve selective inhibition of the COOH domain of TSP-1.

PMID- 11241134
TI  - Supplemental oxygen controls cellular proliferation and anastomotic intimal
      hyperplasia at a vascular graft-to-artery anastomosis in the rabbit.
AB  - PURPOSE: The purpose of this study was to determine whether the administration of
      40% supplemental oxygen (O ( 2) ) will decrease cellular proliferation and
      intimal hyperplasia (IH) at a prosthetic vascular graft (PVG)-to-artery
      anastomosis. METHODS: Twenty New Zealand white rabbits underwent placement of a 3
      mm polytetrafluoroethylene graft in their infrarenal aorta. Four groups of five
      rabbits were placed either in a normoxic (21%) environment or in a 40%
      supplemental O ( 2) environment for 7 or 42 days. Twenty-four hours before the
      rabbits were humanely killed for aortic graft harvest, BrDU (5-bromo-2'
      deoxyuridine) was injected into the rabbits intraperitoneally. Image analysis
      (Bioquant) morphometrics were used to measure cells with BrDU staining and
      intimal areas at the distal anastomosis. Cellular proliferation is defined as
      positively staining BrDU cells divided by all cells in the artery wall. IH is
      reported as a ratio between the intimal area and the medial area to standardize
      the varying aortic size and degree of aortic fixation among rabbits. The Student
      t test was used to compare cellular proliferation and IH between control and O (
      2) -treated rabbits. RESULTS: Cellular proliferation in the intima at 7 days was
      significantly reduced in the O ( 2) -treated animals (1.7% +/- 1%) versus the
      control animals (28.6% +/- 3%) ( P =.0001). The cellular proliferation in the
      intima at 42 days returned to preoperative levels in the O ( 2) -treated group
      (0.15%) and in the control group (0.11%) ( P = not significant). IH at 7 days was
      minimal, and no difference between the O ( 2) -treated group (0.017 +/-.006) and
      the control group (0.009 +/-.03) ( P = not significant) was found. IH was
      significantly reduced at 42 days in the O ( 2) -treated animals (0.031 +/-.012)
      when compared with the control animals (0.193 +/-.043) ( P =.006). CONCLUSIONS:
      Supplemental O ( 2) (40%) significantly reduces cellular proliferation and IH at
      the distal anastomosis of a PVG-to-artery anastomosis in the rabbit model.

PMID- 11241133
TI  - Human vascular smooth muscle cells of diabetic origin exhibit increased
      proliferation, adhesion, and migration.
AB  - PURPOSE: Patients with diabetes mellitus (DM) experience progressive
      macrovascular atherosclerosis and intimal hyperplastic restenosis with increased
      frequency as compared with nondiabetic patients. These observations suggest that
      vascular smooth muscle cells (VSMCs) behave in a phenotypically different and
      more aggressive manner in diabetic patients. In this study, we compared the in
      vitro rates of proliferation, adhesion, and migration of human VSMCs obtained
      from diabetic and nondiabetic patients. METHODS: Human VSMC cultures were
      isolated from 23 diabetic patients (9 artery, 14 vein) and 15 nondiabetic
      patients (9 artery, 6 vein) with extensive lower extremity atherosclerosis. All
      patients were between 61 and 78 years of age (average: 68.4 years [diabetic];
      67.3 years [nondiabetic]). All diabetic patients had type 2 DM. Vascular
      specimens were obtained at the time of amputation from infragenicular arteries
      and during arterial revascularization from saphenous veins. Cells from passages 2
      and 3 were assayed for their proliferative capacity with total DNA fluorescence
      photometry and for adhesion and migration with a modified Boyden chamber.
      RESULTS: The average duration of diabetes was 11.6 +/- 4.1 years. The average
      number of diabetic complications (retinopathy, neuropathy, nephropathy, coronary
      artery disease) was 2.8 +/- 0.7 per patient. Diabetic VSMCs exhibited abnormal
      morphology in cell culture with loss of the normal hill and valley configuration.
      Proliferation was significantly increased in VSMCs of diabetic origin (156 +/- 57
      absorption units) as compared with those of nondiabetic origin (116 +/- 42
      absorption units) (P <.001). Diabetic VSMCs demonstrated significantly greater
      adhesion (63.6 +/- 24 per high-power field vs 37.9 +/- 13 per high-power field; P
      =.002) and migration (397 +/- 151 per low-power field vs 121 +/- 99 per low-power
      field; P =.001) rates. CONCLUSIONS: Diabetic VSMCs exhibit significantly
      increased rates of proliferation, adhesion, and migration as well as abnormal
      cell culture morphology suggestive of abnormal contact inhibition. These
      observations of human VSMCs in culture are consistent with the increased rate of
      infragenicular atherosclerosis and the increased rates of restenosis observed
      clinically in diabetic patients. The atherosclerosis- and intimal hyperplasia
      promoting behavior exhibited appears to be intrinsic to the DM-VSMC phenotype and
      must be considered when designing methods to limit atherosclerosis and intimal
      hyperplasia in diabetic patients.

PMID- 11241135
TI  - Differential proteolytic activity and induction of apoptosis in fibrous versus
      atheromatous plaques in carotid atherosclerotic disease.
AB  - PURPOSE: Atherosclerotic plaque instability may be a contributing factor to
      plaque complications, such as rupture, thrombosis, and embolization. Of the two
      types of plaques, atheromatous and fibrous, the atheromatous type has been
      reported to be vulnerable and unstable. This instability may be related to
      changes in the cell cycle and extracellular matrix degradation. Apoptosis may
      weaken the plaque structurally. In addition, alteration of the cellular component
      may lead to imbalances in associated proteolytic activity. Our study was designed
      to compare the two types of plaques in terms of apoptosis, apoptosis-inducing
      factors, namely Fas/CD95/APO-1 and CPP-32/YAMA/caspase-3, and proteolytic
      activity. METHODS: Carotid artery plaques were obtained from patients undergoing
      endarterectomy and were classified as either atheromatous or fibrous on the basis
      of established criteria. Histologic study included hematoxylin and eosin
      staining, Verhoeff's van Gieson elastin staining, and trichrome staining.
      Detection of apoptosis was performed with the TUNEL assay. Immunohistochemical
      studies were performed to localize the expression of CPP-32/YAMA and Fas/CD95.
      Gelatin gel zymography was used to compare proteolytic activity levels in the two
      types of plaque. RESULTS: Apoptosis was significantly higher (P <.001) in
      atheromatous plaques (4.90% +/- 1.27% [SEM]) as compared with fibrous plaques
      (0.86% +/- 0.46% [SEM]). Zymography demonstrated elevated levels of proteinases
      in atheromatous plaques. Immunohistochemistry revealed significant increases in
      the expression of Fas/CD95 (P <.04) and CPP-32/YAMA (P <.001) in atheromatous
      plaques as compared with that in fibrous plaques. CONCLUSIONS: This is the first
      study comparing molecular factors that render atheromatous plaques more
      susceptible to rupture than fibrous plaques. The higher number of apoptotic cells
      seen in atheromatous plaques as compared with fibrous plaques could contribute to
      their greater instability. Immunoreactivity to cytoplasmic death domain, Fas/CD95
      and CPP-32/YAMA, a prominent mediator of apoptosis, was consistent with the
      numbers of apoptotic cells detected. The increased levels of proteolytic activity
      in atheromatous plaques may make these plaques more prone to rupture. These data
      identifying some of the molecular events and biochemical pathways associated with
      plaque vulnerability may help in the development of new strategies to prevent
      plaque rupture.

PMID- 11241136
TI  - Evaluation of thrombolysis in a porcine model of chronic deep venous thrombosis:
      an endovascular model.
AB  - PURPOSE: The advancement of catheter-based interventions for vascular
      recanalization has underscored the need for an experimental animal model of
      vascular thrombosis that can be used for the evaluation of interventional
      therapies. In this model, a porcine model of deep venous thrombosis with a novel
      endovascular technique was described, and the efficacy of thrombolytic therapy
      with urokinase was evaluated. METHODS: An endovascular device that consisted of a
      tapered polytetrafluoroethylene graft attached within a self-expanding nitinol
      stent was delivered to bilateral common iliac veins in 20 pigs. Venous thrombosis
      occurred as a result of flow stasis created by the intrastent stenosis. Catheter
      directed pulse-spray thrombolysis with urokinase (250,000 units) and heparin
      (5000 IU) was performed on one limb while the contralateral limb received control
      saline solution. Thrombolysis was performed in 1 hour (n = 4), 8 hours (n = 4), 3
      days (n = 4), 7 days (n = 4), and 14 days (n = 4) after the stent-graft
      deployment. Venography and intravascular ultrasound were used to evaluate the
      efficacy of thrombolysis. Light microscopy was used for histologic analysis of
      the thrombus. RESULTS: Complete thrombolysis was achieved in groups with deep
      vein thrombosis that were younger than 1 day. Angioplasty of the tapered stent
      grafts in the completely thrombolysed iliac vein was successful in restoring
      venous flow. The efficacy of thrombolysis in 3-day, 7-day, and 14-day groups was
      86% +/- 7%, 73% +/- 13%, and 42% +/- 23%, respectively. The thrombolytic efficacy
      was enhanced to 92% +/- 16% and 86% +/- 18% (P <.05) in 3-day and 7-day groups,
      respectively, when doses of the pulse-spray thrombolysis were doubled. Increased
      dosages of the thrombolytic agent, however, did not significantly enhance the
      thrombus dissolution in the 14-day group. CONCLUSION: The thrombolytic efficacy
      of urokinase correlated with the chronicity of deep venous thrombosis in our
      model. An increased dose of urokinase may be used to enhance the efficacy of
      thrombolysis in a 1-week-old thrombus.

PMID- 11241137
TI  - Morphologic and mechanical characteristics of engineered bovine arteries.
AB  - OBJECTIVE: The ideal small-caliber arterial graft remains elusive despite several
      decades of intense research. A novel approach to the development of small-caliber
      arterial prostheses with a biomimetic system for in vitro vessel culture has
      recently been described. In this study we examined the effects of culture time
      and tissue culture scaffolding on engineered vessel morphology and function and
      found that these parameters greatly influence the function of engineered vessels.
      METHODS: This report describes the effects of culture time and scaffold type on
      vessel morphology, cellular differentiation, and vessel mechanical
      characteristics. Engineered vessels were cultured from bovine aortic smooth
      muscle cells (SMCs) and endothelial cells that were seeded onto biodegradable
      polymer scaffolds and cultured under physiologically pulsatile conditions.
      Engineered vessels were subjected to histologic, ultrastructural,
      immunocytochemical, and mechanical analyses. RESULTS: Vessel morphology and
      mechanical characteristics improved as time in culture increased to 8 weeks. SMCs
      in the engineered vessel wall were organized into a highly lamellar structure,
      with cells separated by alternating layers of collagen fibrils. Polymer scaffold
      remnants were present in vessels cultured for 8 weeks, and SMCs that were in
      proximity to polymer remnants exhibited a dedifferentiated phenotype.
      CONCLUSIONS: These findings aid in the systematic understanding of the effects of
      in vitro parameters on engineered vessels and will be useful for the translation
      of vessel culture techniques to human cells for the development of autologous
      human vascular grafts.

PMID- 11241138
TI  - Aortic aneurysms in children and young adults with tuberous sclerosis: report of
      two cases and review of the literature.
AB  - Abdominal aortic aneurysms (AAAs) in children and young adults are rare; some
      have been observed in patients with tuberous sclerosis (TS). We report two cases
      and review the literature. A 9-year-old girl with TS was diagnosed with a 3-cm
      calcified AAA, and a 41-year-old man with TS was diagnosed with a 7.5-cm thoracic
      aortic aneurysm (TAA). Both patients underwent open repair with a tube polyester
      graft without complication. They are both doing well at 7 and 8 years after
      surgery. Pathologic evaluation revealed medial atrophy and focal medial
      disruption in the aortic wall in both patients. With our two cases, 15 patients
      with TS and aneurysms have been reported; 12 had AAA, and four had TAA (one
      patient had both). Three AAAs and two TAAs ruptured. Six patients died because of
      aneurysmal disease. There is an association between TS and aortic aneurysms.
      Patients should be screened for aortic aneurysms at the time TS is diagnosed and
      annually thereafter. Because of the high risk of rupture, early elective repair
      is suggested. New aortic aneurysms after repair may also develop.

PMID- 11241139
TI  - Duodenocaval fistula: a life-threatening condition of various origins.
AB  - We report on two cases of duodenocaval fistula. The first patient, a 73-year-old
      man, had sepsis and occult digestive bleeding. We diagnosed a fistula that
      resulted from a right nephrectomy and subsequent radiotherapy for a urothelial
      tumor 20 months earlier. The second patient, a 60-year-old woman, complained of
      right abdominal pain. A duodenocaval fistula that was caused by duodenal
      perforation by a migrating caval filter placed 10 years earlier was revealed by
      means of endoscopy. Both patients had a successful operation to treat the
      condition. An extensive review of the literature disclosed 35 other cases and
      identified two factors of good prognosis: duodenocaval fistulas caused by
      migrating caval filters and early surgery.

PMID- 11241140
TI  - Carbon dioxide angiography for endovascular grafting in high-risk patients with
      infrarenal abdominal aortic aneurysms.
AB  - Allergic reactions to contrast media, preexisting renal dysfunction, and
      hyperthyroidism are relative contraindications for angiography with conventional
      contrast medium. Carbon dioxide (CO(2)) angiography is an alternative method in
      high-risk patients because CO(2) is nontoxic, without allergic potential, and not
      iodic. CO(2)-related complications are extremely rare. Because renal
      insufficiency often occurs in vascular patients, this method will become
      increasingly important for endovascular surgery. We report on three consecutive
      patients with asymptomatic infrarenal aortic aneurysm and concomitant renal
      dysfunction or allergic reactions to standard contrast media. Aortic stent grafts
      were deployed under CO(2) angiographic control without complications or worsening
      of renal function.

PMID- 11241142
TI  - Shopping for vascular surgery.

PMID- 11241141
TI  - The carotid artery as alternative access for endoluminal aortic aneurysm repair.
AB  - Endograft treatment of aortic aneurysms has become a common procedure in many
      centers. However, not all patients are candidates for this new technology,
      because of their vascular anatomy and device limitations. One common problem is
      iliofemoral occlusive disease, which when present, even in a moderate degree, may
      preclude introduction of the large-diameter delivery devices currently in use. We
      present a case of a high-risk male patient with a thoracic aortic aneurysm and
      severe occlusive disease of the iliac arteries. An alternative approach for
      device delivery through the carotid artery was used and the procedure was
      successful with no neurologic complications. We recommend this technique for
      highly selected patients with an aneurysm who can undergo tube endograft repair
      without feasible access through the iliac or femoral arteries.

PMID- 11241143
TI  - Regarding "recurrent thromboembolism in patients with vena caval filters".

PMID- 11241144
TI  - Regarding "a comparative evaluation of polytetrafluoroethylene, umbilical vein,
      and saphenous vein bypass grafts for femoral-popliteal above-knee
      revascularization: a prospective randomized Department of Veterans Affairs
      cooperative study".

PMID- 11241146
TI  - Regarding "ambulatory venous pressure revisited".

PMID- 11241148
TI  - Regarding "thrombus within an aortic aneurysm does not reduce pressure on the
      aneurysm wall".

PMID- 11241150
TI  - Regarding "acute enlargement and subsequent rupture of an abdominal aortic
      aneurysm in a patient receiving chemotherapy for pancreatic carcinoma".

PMID- 11241152
TI  - Regarding "crushed stents in benign left brachiocephalic vein stenoses".

PMID- 11241154
TI  - Regarding "Dacron carotid patch infection: a report of eight cases".

PMID- 11241156
TI  - Regarding "management of leg ulcers in patients with rheumatoid arthritis or
      systemic sclerosis: the importance of concomitant arterial and venous disease".

PMID- 11241158
TI  - Regarding "comparing patency rates between external iliac and common iliac
      stents".

PMID- 11241160
TI  - Osteoporosis, genetics and hormones.
AB  - Osteoporosis is a systemic skeletal disease characterized by low bone mass and
      microarchitectural deterioration of bone tissue. At a given age, bone mass
      results from the amount of bone acquired during growth, i.e. the peak bone mass
      (Bonjour et al., 1991, Theintz et al. 1992) minus the age-related bone loss which
      particularly accelerates after menopause. The rate and magnitude of bone mass
      gain during the pubertal years and of bone loss in later life may markedly differ
      from one skeletal site to another, as well as from one individual to another.
      Bone mass gain is mainly related to increases in bone size, that is in bone
      external dimensions, with minimal changes in bone microarchitecture. In contrast,
      postmenopausal and age-related decreases in bone mass result from thinning of
      both cortices and trabeculae, from perforation and eventually disappearance of
      the latter, leading to significant alterations of the bone microarchitecture
      (Fig. 1).

PMID- 11241161
TI  - Elevated expression of proprotein convertases alters breast cancer cell growth in
      response to estrogen and tamoxifen.
AB  - Two proprotein convertase cDNAs, PC1 and furin, were stably transfected into the
      human breast cancer cell line MCF-7. The PC1 or furin over-expressing cells
      possessed an altered morphology. When grown in vitro in a serum-free medium, the
      population doubling time of the convertase-transfected cells was twice that of
      wild-type (WT) cells. High concentrations of estradiol stimulated the growth of
      all three cell types to a similar extent; however, at low concentrations of
      estradiol, the convertase-transfected cells grew more slowly than WT cells. In
      athymic nude mice implanted with 5 mg estradiol pellets, the growth of tumors of
      convertase-transfected MCF-7 cells was stimulated to a degree similar to that of
      WT MCF-7 tumors. However, in mice implanted with lower-dose (1.5 mg) estradiol
      pellets, the tumors of PC1- or furin-transfected MCF-7 cells grew approximately
      five times slower than those of WT MCF-7 cells. In mice implanted with tamoxifen
      pellets, tumors of PC1- or furin-transfected MCF-7 cells regressed approximately
      five times slower than the WT tumors. This study shows that the over-expression
      of proprotein convertases confers a greater estrogen dependency and anti-estrogen
      resistance on human breast cancer cells.

PMID- 11241162
TI  - Genomic organization of the gene coding for human pre-B-cell colony enhancing
      factor and expression in human fetal membranes.
AB  - Pre-B-cell colony enhancing factor (PBEF) was first isolated from an activated
      peripheral blood lymphocyte cDNA library and was found to be involved in the
      maturation of B-cell precursors. It was subsequently identified as one of the
      genes upregulated by distending the human fetal membranes in vitro. Here we
      report on the genomic organization of this gene, which is composed of 11 exons
      and 10 introns, spanning 34.7 kb of genomic DNA. Neither the gene nor the protein
      has any homology with other cytokines in any currently available database. The
      use of two promoters (proximal and distal) may result in differential, tissue
      specific expression of the PBEF transcripts. The 5'-flanking region lacks the
      classical sequence motif that would place it with the hematopoietic cytokines;
      however, it has several putative regulatory elements, suggesting that this gene
      may be chemically and mechanically responsive to inducers of transcription. The
      three PBEF mRNA transcripts were observed in both normal and infected human fetal
      membranes but were significantly upregulated (P<0.05) in severe infection. The
      PBEF protein was immunolocalized, in both normal and infected tissues, to both
      the normal fetal cells of the amnion and chorion and the maternal decidua of the
      membranes, and to the invading neutrophils. These stained strongly and were
      likely to contribute to the increased expression in infection. The amniotic
      epithelial cell line (WISH cells) has been used as a model to study PBEF gene
      modulation. Lipopolysaccharide, interleukin (IL)-1beta, tumour necrosis factor
      (TNF)alpha and IL-6 all significantly increased the expression of PBEF in 4 h of
      treatment. The addition of dexamethasone to IL-1beta and TNFalpha significantly
      reduced the response of PBEF to these cytokines. IL-8 treatment failed to alter
      PBEF gene expression. Thus PBEF is a cytokine expressed in the normal fetal
      membranes and upregulated when they are infected. It is likely to have a central
      role in the mechanism of infection-induced preterm birth.

PMID- 11241163
TI  - Adrenal and sex steroid receptor evolution: environmental implications.
AB  - The nuclear receptor family responds to a diverse group of ligands, including
      steroids, retinoids, thyroid hormone, prostaglandins and fatty acids. Previous
      sequence analyses of adrenal and sex steroid receptors indicate that they form a
      clade separate from other nuclear receptors. However, the relationships of
      adrenal and sex steroid receptors to each other and to their ancestors are not
      fully understood. We have used new information from androgen, estrogen,
      mineralocorticoid and progesterone receptors in fish to better resolve the
      phylogeny of adrenal and sex steroid receptors. Sequence divergence between fish
      and mammalian steroid receptors correlates with differences in steroid
      specificity, suggesting that phylogeny needs to be considered in evaluating the
      endocrine effects of xenobiotics. Among the vertebrate steroid receptors, the
      most ancient is the estrogen receptor. The phylogeny indicates that adrenal and
      sex steroid receptors arose in a jawless fish or a protochordate and that changes
      in the sequence of the hormone-binding domain have slowed considerably in land
      vertebrates. The retinoid X receptor clade is closest to the adrenal and sex
      steroid receptor clade. Retinoid X receptor is noteworthy for its ability to form
      dimers with other nuclear receptors, an important mechanism for regulating the
      action of retinoid X receptor and its dimerization partners. In contrast, the
      adrenal and sex steroid receptors bind to DNA as homodimers. Moreover, unliganded
      adrenal and sex steroid receptors form complexes with heat shock protein 90.
      Thus, the evolution of adrenal and sex steroid receptors involved changes in
      protein-protein interactions as well as ligand recognition.

PMID- 11241164
TI  - Regulation of phosphatidylinositol-phosphate kinase IIgamma gene transcription by
      thyroid-stimulating hormone in thyroid cells.
AB  - This study was performed to evaluate the effects of thyroid-stimulating hormone
      (TSH) on phosphatidylinositol-4-phosphate 5-kinase type IIgamma (PIPKIIgamma)
      gene expression in the thyrocytes of FRTL-5 cells. Although PIPKIIgamma mRNA was
      expressed constantly in the absence of added TSH, its expression increased
      remarkably in the presence of 10(-9) M TSH. This increase started within 6 h of
      the addition of TSH, and reached a maximum at 8 h. The mRNA expression properties
      of PIPKIIgamma in the cells were identified using inhibitors. Actinomycin D
      blocked PIPKIIgamma transcription strongly, while cycloheximide did not. In an
      experiment using 5,6-dichlo-1-beta-d -ribofuranosylbenzimidaxole, the half-life
      of PIPKIIgamma mRNA was approximately 6 h in the presence or absence of TSH, and
      it was not affected by the stability of the PIPKIIgamma mRNA. The effects of TSH
      on PIPKIIgamma gene expression were specific, and other growth factors examined
      (transferrin, insulin and hydrocortisone) did not alter its expression. It is
      possible that the mechanism of PIPKIIgamma gene expression is involved in the
      permissive effect of the TSH-cAMP cascade proper. Our results indicate, for the
      first time, that the expression of PIPKIIgamma is regulated transcriptionally by
      TSH in thyrocytes.

PMID- 11241165
TI  - Molecular cloning of the porcine acid-labile subunit (ALS) of the insulin-like
      growth factor-binding protein complex and detection of ALS gene expression in
      hepatic and non-hepatic tissues.
AB  - The acid-labile subunit (ALS) is an approximately 85 kDa N-glycoprotein that is
      known primarily as a component of the systemic insulin-like growth factor-binding
      protein (IGFBP) complex. We have amplified, using a PCR, three overlapping
      porcine ALS genomic DNA fragments that together encode the distal region of the
      signal peptide through to the COOH-terminus. The compiled sequence of 1775
      nucleotides of the three overlapping DNAs and the deduced amino acid sequence of
      the mature porcine ALS (pALS) protein exhibited 84/81%, 79/77%, 79/78% and 84/79%
      identities with respect to those of the human, the rat, the mouse and the baboon
      respectively. Four conserved cysteine residues in the NH(2)-terminal domain and
      20 leucine-rich repeats in the central domain also were identified at identical
      positions in the porcine ALS. By using Northern blot analysis, with a genomic DNA
      fragment as the probe, it was determined that a 2.2 kb ALS mRNA was induced in
      the liver during the late fetal stage, and hepatic ALS mRNA abundance was
      increased post-natally. Moreover, hepatic ALS mRNA abundance was increased by
      daily injection of porcine somatotropin (100 microg/kg body weight) in cross-bred
      market pigs each weighing approximately 100 kg. The ALS mRNA was not detected by
      Northern analysis in any non-hepatic tissue examined. However, results of a more
      sensitive solution hybridization/RNAse protection assay indicated that low levels
      of ALS mRNA were also present in adult muscle, spleen, ovary and uterus, but not
      in lung, kidney, oviduct and placenta. Taken together, the present results
      suggest that although liver is the primary organ that expresses the ALS gene
      under somatotropin stimulation, some non-hepatic tissues also express the gene at
      low levels in the pig.

PMID- 11241166
TI  - Fatty acids inhibit leptin signalling in BRIN-BD11 insulinoma cells.
AB  - The effect of treatment with a 0.03% fatty acid (FA) cocktail on leptin-receptor
      mediated STAT (signal transducers and activators of transcription) activation in
      the rat insulinoma cell line BRIN-BD11 was investigated. Leptin (10 nM)
      stimulated the tyrosine phosphorylation of STAT3 and STAT5b. Acute treatment with
      FAs prevented leptin-stimulated STAT3 tyrosine phosphorylation and significantly
      raised basal STAT5 phosphorylation. A chronic treatment (5 days) of BRIN-BD11
      cells with FAs similarly attenuated leptin-stimulated STAT tyrosine
      phosphorylation. Chronic FA treatment also attenuated prolactin-stimulated STAT5b
      tyrosine phosphorylation but not interleukin-6-stimulated STAT3 tyrosine
      phosphorylation, suggesting that the effect is receptor/ligand specific. TaqMan
      analysis of gene expression following chronic FA treatment showed neither a
      decrease in the amount of leptin receptor (Ob-R) mRNA, nor an increase in the
      negative regulators of STAT signalling, SOCS3 (suppressors of cytokine
      signalling) or cytokine inducible sequence (CIS). These data demonstrate that FAs
      modulate leptin and prolactin signalling in beta-cells, implying that high levels
      of circulating FAs present in obese individuals affect the action of selective
      cytokines in beta-cell function.

PMID- 11241167
TI  - Osteoporosis in men: a cellular endocrine perspective of an increasingly common
      clinical problem.
AB  - Although it has been accepted that osteoporosis is common in women, only recently
      have we become aware that it is also widespread in men; one in twelve men in the
      UK have osteoporosis. In many cases, there are recognisable causes for their
      osteoporosis, but a significant proportion (approximately one third) of these men
      have idiopathic disease. A major problem is that these cases are difficult to
      treat. An important therapeutic strategy would be to identify men at risk from
      osteoporosis sufficiently early, so that they can begin preventative measures.
      Moreover, development of novel means of treating these men would be an important
      clinical advance. With the emphasis on osteoporosis in women, however, the
      cellular and molecular basis for male idiopathic osteoporosis (MIO) is still
      poorly understood. Nevertheless, there are some aspects of skeletal regulation
      which may be specific for men and which could form the basis for addressing these
      problems. Thus, the importance of oestrogen in maintaining the adult skeleton in
      men as well as women implies that bone cells in men can respond to low levels of
      the hormone. Both oestrogen receptor (ER) alpha and beta are expressed in bone in
      vivo, which may be important for oestrogen action on bone in men. Furthermore, in
      osteoporosis generally, there is increasing evidence for defective osteoblast
      differentiation such that there is a surfeit of adipocytes over osteoblasts. A
      low peak bone mass is a powerful risk factor for osteoporosis in later life; bone
      formation and, by implication, osteoblast differentiation, is key to the
      mechanism by which it is accrued. GH and IGFs are important for regulating
      osteoblast differentiation. Evidence now suggests that they are associated with
      bone mineral density, particularly in men. The genes for ERs, GH and IGF-I might
      be useful candidates with which we can begin to detect men at risk from
      osteoporosis. Furthermore, the mechanisms by which oestrogen, GH and IGF-I
      regulate the male skeleton could provide the basis for developing novel means of
      treating MIO.

PMID- 11241168
TI  - Identification, cellular and subcellular distribution of 21 and 72 kDa proteins
      (tuberalins?) secreted by specific cells of the pars tuberalis.
AB  - The cell types of the pars tuberalis (PT) are the follicular cells, the pars
      distalis cells and the so-called PT-specific cells. The latter are distinct
      endocrine cells displaying melatonin receptors. Although the nature of the
      secretory product(s) of the PT-specific cells has not yet been clarified, the
      function of these cells has started to be unfolded. For practical reasons,
      previous authors have designated the, as yet, unidentified PT hormone(s) as
      tuberalin(s). PT-specific cells synthesise the common alpha subunit of the pars
      distalis glycoprotein hormones, and it has been suggested that tuberalin would
      correspond to the beta chain of a specific glycoprotein secreted by these cells.
      The aims of the present investigation were to identify the compounds secreted by
      the specific cells of bovine PT, and to establish their cellular and subcellular
      distribution. For this purpose, proteins secreted into the culture medium of PT
      explants were separated by electrophoresis and used to raise antibodies. Two of
      these proteins, with an apparent molecular mass of 21 and 72, generated
      antibodies (Ab-21 and Ab-72) that differentially immunoreacted with PT-specific
      cells. These two antibodies were used for immunoblotting of conditioned medium
      and of PT explants, and for light and electron microscopy immunocytochemistry. In
      immunoblots, Ab-21 reacted with compounds of 21, 22, 47 and 52 kDa, whereas Ab-72
      revealed a compound of 72 kDa only. Ab-72 immunoreactive material corresponded to
      a protein, here designated as tuberalin I, secreted by a small population of PT
      specific cells (type 2 cells), and stored in 140 nm secretory granules.
      Immunoreactive tuberalin I was missing from bovine pars distalis and from rat PT.
      The predominant population of PT-specific cells (type 3 cells) secreted and
      stored, within 280 nm secretory granules, an Ab-21 immunoreactive protein, here
      designated as tuberalin II. All cells of rat PT immunoreacted with Ab-21. In the
      cells of bovine and rat PT, immunoreactive tuberalin II was mostly confined to a
      paranuclear spot; this spot also bound wheat germ agglutinin and reacted with an
      antibody against the alpha chain of glycoprotein pars distalis hormones. It is
      suggested that tuberalin II would correspond to the beta chain of a specific
      glycoprotein secreted by type 3 PT-specific cells. In bovine PT, the cells
      displaying immunoreactive tuberalins I and II did not react with any of the
      antibodies against pars distalis hormones.

PMID- 11241169
TI  - cfos and cjun antisense oligonucleotides block mitogenesis triggered by
      fibroblast growth factor-2 and ACTH in mouse Y1 adrenocortical cells.
AB  - In G(0)/G(1) cell cycle-arrested mouse Y1 adrenocortical cells, short pulses (30
      min to 2 h) of fibroblast growth factor-2 (FGF2) (5 pM to 1 nM) caused induction
      of cFos protein by 2 h and onset of DNA synthesis stimulation by 8-9 h. FGF2 dose
      response curves for cFos induction (percent labeled nuclei with a specific anti
      cFos antibody) and DNA synthesis stimulation (bromodeoxyuridine labeling index)
      were linearly correlated with a correlation coefficient of 0.969. Inhibition of
      cFos and cJun protein induction with antisense oligodeoxynucleotides (ODNs) to
      cfos and cjun mRNAs blocked DNA synthesis stimulation by FGF2. Pulses (up to 2 h)
      of synthetic ACTH(39) (1 pM to 1 nM) and natural porcine corticotropin A (10
      pg/ml to 1 microg/ml) also induced cFos protein and DNA synthesis in G(0)/G(1)
      arrested Y1 adrenal cells. ACTH dose-response curves for cFos induction and DNA
      synthesis stimulation were not correlated. But cfos and/or cjun antisense ODNs
      blocked DNA synthesis stimulation by ACTH. Thus, signals initiated in FGF2 and
      ACTH receptors appear to converge to the induction of cfos and cjun genes to
      trigger DNA synthesis stimulation.

PMID- 11241170
TI  - Deltins: immunochemical evidence for a novel population of peptides of the D
      cells of the gastro-entero-pancreatic endocrine system.
AB  - Differences between the immunocytochemical behaviour of antisera to partially
      purified porcine gastrins and antisera to either synthetic human gastrin-17-I or
      highly purified porcine gastrin-17-I raised the hypothesis that hog antral
      gastrin extracts contain peptides different from somatostatin and gastrin that
      are responsible for the immunocytochemical reaction of the former antisera in the
      D (delta) cells of the gastro-entero-pancreatic (GEP) endocrine system. This
      study was performed to prove this hypothesis. A discard fraction obtained after
      gel filtration of hog antral gastrin extracts on Sephadex G-50 Superfine was
      employed to immunize five rabbits. The discard fraction is highly heterogeneous
      on two-dimensional electrophoresis and contains merely traces of somatostatin and
      gastrin in RIA. However, rabbit antisera to the discard fraction give strongly
      positive immunocytochemical reactions exclusively in the D cells of the human
      antroduodenal mucosa and of the pancreatic islets. Absorption of the antisera
      with the lyophilized discard fraction abolishes the staining of the D cells,
      whereas absorption of the antisera with several somatostatins does not affect the
      staining. Vice versa, staining of the D cells with antisera to cyclic
      somatostatin-14 is abolished by absorption of the antisera with somatostatin-14
      but not by absorption with excess of the discard fraction. In RIA, antisera to
      the discard fraction do not bind radiolabelled (Tyr(1))-somatostatin-14, Tyr
      somatostatin-28 or synthetic human gastrin-17-I. Two-dimensional electrophoresis
      of acid extracts of isolated canine pancreatic islets followed by Western
      blotting shows different patterns of distribution of immunoreactive spots
      obtained with antisera to the discard fraction, to somatostatin-14, and to human
      proinsulin respectively. These results indicate the existence of a novel
      population of peptides of the D cells of the GEP endocrine system, for which we
      propose the term deltins.

PMID- 11241171
TI  - Androgen receptors are only present in mesenchyme-derived dermal papilla cells of
      red deer (Cervus elaphus) neck follicles when raised androgens induce a mane in
      the breeding season.
AB  - Red deer stags produce an androgen-dependent mane of long hairs only in the
      breeding season; in the non-breeding season, when circulating androgen levels are
      low, the neck hair resembles the rest of the coat. This study was designed to
      determine whether androgen receptors are present in deer follicles throughout the
      year or only in the mane (neck) follicles when circulating testosterone levels
      are high in the breeding season. Although androgens regulate much human hair
      growth the mechanisms are not well understood; they are believed to act on the
      hair follicle epithelium via the mesenchyme-derived dermal papilla. The location
      of androgen receptors in the follicle was investigated by immunohistochemistry
      and androgen binding was measured biochemically in cultured dermal papilla cells
      derived from mane and flank follicles during the breeding season and from neck
      follicles during the non-breeding season. Immunohistochemistry of frozen skin
      sections using a polyclonal antibody to the androgen receptor localised nuclear
      staining only in the dermal papilla cells of mane follicles. Saturation analysis
      assays of 14 primary dermal papilla cell lines using [(3)H]-mibolerone
      demonstrated high-affinity, low-capacity androgen receptors were present only in
      mane (breeding season neck) cells; competition studies with other steroids
      confirmed the specificity of the receptors. Androgen receptors were not
      detectable in cells from either the breeding season flank nor the non-breeding
      season neck follicles. The unusual biological model offered by red deer of
      androgen-dependent hair being produced on the neck in the breeding, but not the
      non-breeding season, has allowed confirmation that androgen receptors are
      required in follicle dermal papilla cells for an androgen response; this concurs
      with previous human studies. In addition, the absence of receptors in the non
      breeding season follicles demonstrates that receptors are not expressed unless
      the follicle is responding to androgens. Androgen receptors may be induced in
      mane follicles by seasonal changes in circulating hormone(s).

PMID- 11241172
TI  - Mid-luteal angiogenesis and function in the primate is dependent on vascular
      endothelial growth factor.
AB  - Vascular endothelial growth factor (VEGF) is essential for the angiogenesis
      required for the formation of the corpus luteum; however, its role in ongoing
      luteal angiogenesis and in the maintenance of the established vascular network is
      unknown. The aim of this study was to determine whether VEGF inhibition could
      intervene in ongoing luteal angiogenesis using immunoneutralisation of VEGF
      starting in the mid-luteal phase. In addition, the effects on endothelial cell
      survival and the recruitment of periendothelial support cells were examined.
      Treatment with a monoclonal antibody to VEGF, or mouse gamma globulin for control
      animals, commenced on day 7 after ovulation and continued for 3 days.
      Bromodeoxyuridine (BrdU), used to label proliferating cells to obtain a
      proliferation index, was administered one hour before collecting ovaries from
      control and treated animals. Ovarian sections were stained using antibodies to
      BrdU, the endothelial cell marker, CD31, the pericyte marker, alpha-smooth muscle
      actin, and 3' end DNA fragments as a marker for apoptosis. VEGF
      immunoneutralisation significantly suppressed endothelial cell proliferation and
      the area occupied by endothelial cells while increasing pericyte coverage and the
      incidence of endothelial cell apoptosis. Luteal function was markedly compromised
      by anti-VEGF treatment as judged by a 50% reduction in plasma progesterone
      concentration. It is concluded that ongoing angiogenesis in the mid-luteal phase
      is primarily driven by VEGF, and that a proportion of endothelial cells of the
      mid-luteal phase vasculature are dependent on VEGF support.

PMID- 11241173
TI  - Differentiation of human parathyroid cells in culture.
AB  - Continuous culture of parathyroid cells has proven difficult, regardless from
      which species the cells are derived. In the present study, we have used a defined
      serum-free low calcium containing medium to culture human parathyroid cells
      obtained from patients with parathyroid adenomas due to primary
      hyperparathyroidism. No fibroblast overgrowth occurred, and the human parathyroid
      chief cells proliferated until confluent. After the first passage the cells
      ceased to proliferate, but still retained their functional capacity up to 60
      days, demonstrated by Ca(2+)-sensitive changes in the release of parathyroid
      hormone (PTH) and as adequate cytoplasmic calcium ([Ca2+](i)) responses to
      changes in ambient calcium as measured by microfluorimetry. Low calcium
      concentrations enhanced, and vitamin D(3) and retinoic acids (RA) dose
      dependently inhibited cell proliferation during the first passage, as determined
      by [(3)H]thymidine incorporation, immunohistochemistry for proliferating cell
      nuclear antigen and cell counting. Signs of differentiation were present as the
      set-points, defined as the external calcium concentration at which half-maximal
      stimulation of [Ca2+](i) (set-point(c)), or half-maximal inhibition of PTH
      release (set-point(p)) occur, were higher in not proliferating compared with
      proliferating cells in P0. Inhibition of cell proliferation was accompanied by
      signs of left-shifted set-points, indicating a link between proliferation and
      differentiation. The results demonstrate that human parathyroid chief cells
      cultured in a defined serum-free medium can be kept viable for a considerable
      time, and that signs of differentiation occur after proliferation has ceased. The
      low calcium stimulated cell proliferation may also be inhibited by vitamin D and
      RA.

PMID- 11241174
TI  - The biological relevance of thyroid hormone receptors in immortalized human
      umbilical vein endothelial cells.
AB  - The gene expression of thyroid hormone receptors (TR) in ECRF24 immortalized
      human umbilical vein endothelial cells (HUVECs) was investigated at both the mRNA
      and the protein level. Endothelin-1 (ET-1) and von Willebrand factor (vWF)
      production were measured in response to triiodothyronine (T(3)) administration. A
      real-time PCR technique was used to quantify the presence of mRNAs encoding for
      the different isoforms of the TR. The binding of T(3) to nuclear TRs was studied
      in isolated endothelial cell nuclei by Scatchard analysis. Expression of TR at
      the protein level was investigated by immunocytochemistry and Western blotting
      using TR-isoform-specific polyclonal rabbit antisera. ET-1 and vWF were measured
      in cell supernatants with a two-site immunoenzymatic assay. Scatchard analysis
      yielded a maximum binding capacity of 55 fmol T(3)/mg DNA (+/-200 sites/cell)
      with a K(d) of 125 pmol/l. Messenger RNAs encoding for the TRalpha1 and the
      TRalpha2 and the TRbeta1 were observed. The approximate number of mRNA molecules
      per cell was at least 50 molecules per cell for TRalpha1, five for TRalpha2 and
      two for TRbeta1. Immunocytochemistry revealed (peri)nuclear staining for TRbeta1,
      TRalpha1 and TRalpha2. ET-1 and vWF secretion did not increase upon addition of
      T(3) (10(-10)-10(-6) M). Immortalized ECRF24 HUVECs express TR, but at low
      levels. The number of TRs per endothelial cell is probably too low to be
      functional and no change in ET-1 or vWF production was found after addition of
      T(3). Therefore we conclude that the genomic effects of T(3) are unlikely to
      occur in these immortalized HUVECs.

PMID- 11241175
TI  - Water metabolism disturbances at different stages of primary thyroid failure.
AB  - The aim of the present study was to study salt and water metabolism in thyroid
      deficiency. We performed an oral water loading test (OWL) and a hypertonic 5%
      saline infusion test (HSI) in 16 patients with overt primary hypothyroidism
      before replacement treatment (PRE group) and after, in eight patients with
      subclinical hypothyroidism (SUB group) and in 16 normal individuals (CG group).
      In the PRE group, a lower free water clearance was detected in the OWL (P <
      0.022), with lower plasma osmolality (OWL: P < 0.005; HSI: P < 0.001) and
      arginine vasopressin (AVP) (OWL: P < 0.001; HSI: P < 0.001) than the CG group,
      across both tests; they normalized with the replacement treatment. The same
      plasma abnormalities were detected in the SUB group with the HSI. Although the
      AVP and thirst thresholds did not differ between the groups, the lag between them
      was lower in the PRE (4.1+/-3.2 mOsm/kg) and SUB group (2.6+/-2.1 mOsm/kg) than
      in the CG group (13.3+/-9.2 mOsm/kg) (P < 0.05). There were no differences in
      atrial natriuretic hormone (ANH), plasma renin activity (PRA) and plasma
      aldosterone among the groups. These results indicate that plasma hypo-osmolality
      and low levels of AVP are present in primary hypothyroidism, and indeed are
      already present in the subclinical phase of the disease. An overlap between the
      thresholds of thirst and AVP seem to play a role in these abnormalities, but ANH,
      PRA and plasma aldosterone do not appear to contribute.

PMID- 11241176
TI  - Estrogen receptors alpha and beta in the normal, hyperplastic and carcinomatous
      human prostate.
AB  - Two different estrogen receptors (ER-alpha and ER-beta) have been described,
      which are differentially involved in regulating the normal function of
      reproductive tissues. ER-alpha was considered for a long time to be the only
      estrogen receptor, and it has been detected in the stromal cells of the human
      prostate but not in the epithelium. To obtain new information about the
      differential effects of both receptor types, we have investigated their
      localization in normal prostates, benign prostatic hyperplasia (BPH), and
      prostatic cancer (PC) by immunohistochemistry, ELISA and Western blot. Epithelial
      immunostaining was absent in normal prostates and was present in BPH (10% of
      cells) and PC (80% of cells), whereas about 15% of stromal cells were positively
      immunostained for ER-alpha in the three types of prostatic specimens studied.
      Epithelial immunostaining for ER-beta was detected in normal prostates (13% of
      cells), BPH (30% of cells) and PC (79% of cells), whereas stromal immunostaining
      for ER-beta was absent in normal and hyperplastic prostates and was present in PC
      (12% of cells). The complementary presence of both receptor types in the normal
      prostate (ER-beta in the epithelium and ER-alpha in the stroma) might explain the
      mechanism of estrogen action in the development of BPH. The increased epithelial
      immunostaining for both ER-alpha and ER-beta in BPH and PC suggests that the
      involvement of estrogen receptors in hyperplasia and cancer concerns mainly the
      epithelium.

PMID- 11241178
TI  - Identification and characterization of insulin-like growth factor (IGF)-binding
      protein expression and secretion by adult human adrenocortical cells:
      differential regulation by IGFs and adrenocorticotropin.
AB  - In previous studies we have shown that IGF-II stimulates basal as well as ACTH
      induced cortisol secretion from adult human adrenocortical cells more potently
      than IGF-I, and that both IGFs predominantly stimulate androgen biosynthesis. The
      steroidogenic effect of IGF-I and IGF-II is mediated through interaction with the
      IGF-I receptor, and modified by locally produced IGF-binding proteins (IGFBPs).
      In the present study, we identified and characterized IGFBP synthesis in normal
      adult human adrenocortical cells in primary culture, and investigated the effect
      of ACTH and recombinant human IGF-I and -II on the regulation of IGFBP expression
      and secretion. Using RT-PCR, we identified the mRNA of all six high-affinity
      IGFBPs, in both adrenocortical tissue and monolayer cell cultures of
      adrenocortical cells. Using Western ligand and immunoblotting and two-dimensional
      Western ligand blotting we confirmed the secretion of IGFBP-1, -2, -3, -4 and -5
      by adrenocortical cells in primary culture. The quantification of IGFBPs
      indicated that IGFBP-3 accounts for almost half the binding activity in
      conditioned medium of unstimulated cells (47%), followed by IGFBP-4 (20%), IGFBP
      5 (15%), IGFBP-2 (12%) and IGFBP-1 (6%). After treatment with ACTH, the abundance
      of IGFBP-1 was upregulated significantly 2.6-fold, while IGFBP-3 was induced only
      slightly (1.3-fold). IGFBP-2, -4 and -5 remained unchanged. In contrast, IGF-I
      and -II (6.5 nM) predominantly induced the abundance of IGFBP-5 (2- and 1.6-fold
      respectively) and IGFBP-3 (2- and 1.7-fold respectively), while IGFBP-1, -2 and 
      4 were unaltered. The induction of IGFBP-1 and -5 by ACTH and IGFs, respectively,
      was paralleled by an increase in the amount of IGFBP-1 and -5 mRNA in these
      cells. In conclusion, all six high-affinity IGFBPs are expressed in the adult
      human adrenal gland, and the presence of at least five high-affinity IGFBPs has
      been demonstrated in conditioned medium of adult human adrenocortical cells.
      Furthermore, the expression and secretion of IGFBP-1 is upregulated by ACTH,
      whereas IGFBP-5 is induced by IGF-I and -II. Together with earlier findings,
      these results suggest that IGFBPs play an important modulatory role in the
      regulation of the differentiated adrenocortical function.

PMID- 11241177
TI  - Oestrogen at the neonatal stage is critical for the reproductive ability of male
      mice as revealed by supplementation with 17beta-oestradiol to aromatase gene
      (Cyp19) knockout mice.
AB  - Aromatase P450 (CYP19) is an enzyme responsible for the conversion of androgens
      to oestrogens. We generated CYP19 knockout (ArKO) mice by targeted disruption of
      Cyp19 and studied the role of oestrogens in male reproductive ability.
      Approximately 85% of ArKO males were unable to sire offspring. However, no
      obvious difference was found in testicular and epididymal weights, numbers of
      sperm in the epididymis or the ability of sperm to fertilize eggs in vitro
      between wild-type and ArKO males. An examination of mating behaviour demonstrated
      that ArKO males showed an impairment in mounting behaviour against sexually
      mature females. The inability of more than 90% of ArKO males to sire offspring
      was reversed by repeated subcutaneous injections of 17beta-oestradiol when
      initiated on the day of birth. The effects of 17beta-oestradiol on reproduction
      were concentration dependent and evident when supplementation was initiated on
      day 7, but not on day 15 after birth. These findings suggest that oestrogens
      acting during neonatal life are required for normal mating behaviour in
      adulthood.

PMID- 11241179
TI  - The role of the pituitary gland and ACTH in the regulation of mRNAs encoding
      proteins essential for adrenal steroidogenesis in the late-gestation ovine fetus.
AB  - To further understand the relative roles of the pituitary gland and ACTH in the
      regulation of mRNAs encoding proteins that are essential for adrenal development,
      we investigated the effects of, first, an ACTH infusion and labour in intact
      fetuses and, secondly, the effect of an ACTH infusion to fetuses with and without
      a pituitary gland, on the relative abundance of the mRNA encoding for the ACTH
      receptor (MC2R), steroidogenic factor 1 (SF-1), cholesterol side-chain cleavage
      enzyme (P450(scc)), 3beta-hydroxysteroid dehydrogenase (3betaHSD) and 17alpha
      hydroxylase (P450(C17)) in the fetal adrenal gland. ACTH(1-24) infusion (14.7
      pmol/kg per h) to intact fetuses was without effect on the abundance of mRNA
      encoding MC2R and SF-1, irrespective of whether the infusion was given for 18
      (115-132 days of gestation) or 32 days (115 days to term (147 days of
      gestation)). Hypophysectomy (HX) did not alter the expression of MC2R mRNA;
      however, the abundance of SF-1 mRNA fell by approximately 50% following the
      removal of the pituitary gland. ACTH(1-24) infusion to HX fetuses failed to
      restore levels of SF-1 mRNA to that seen in intact animals. P450(scc) and
      3betaHSD mRNAs were increased by ACTH(1-24) infusion for 18 days in intact
      animals, although no effects of the infusion were seen on P450(C17) mRNA levels.
      For all three of these mRNAs, there was a significant increase in their abundance
      between 132 days of gestation and term in intact fetuses. By term, ACTH(1-24)
      infusion was without any additional effect on their abundance. HX decreased the
      expression of P450(scc), 3betaHSD and P450(C17) mRNAs, while ACTH(1-24) infusion
      to HX fetuses increased the expression of these mRNAs to levels seen in intact
      animals. There were significant correlations between the abundance of the mRNA
      for P450(scc), 3betaHSD and P450(C17), but not MC2R and SF-1, and premortem
      plasma cortisol concentrations. These results emphasise the importance of the
      pituitary gland and ACTH in the regulation of the enzymes involved in adrenal
      steroidogenesis. Factors in addition to ACTH may also play some role, as the
      infusion was not always effective in increasing the abundance of the mRNAs.
      Surprisingly, the mRNA for MC2R and SF-1 did not appear to be regulated by ACTH
      in the late-gestation ovine fetus, though a pituitary-dependent factor may be
      involved in the regulation of SF-1 mRNA abundance.

PMID- 11241180
TI  - Reconstituted normal human breast in nude mice: effect of host pregnancy
      environment and human chorionic gonadotropin on proliferation.
AB  - The proliferation of normal human breast epithelial cells in women is highest
      during the first trimester of pregnancy. In an attempt to analyze this hormonal
      environment in a model system, the effect of host mouse pregnancy and the
      administration of human chorionic gonadotropin (hCG) were assessed in normal
      human breast epithelial cells transplanted into athymic nude mice. Human breast
      epithelial cells, dissociated from reduction mammoplasty specimens and embedded
      inside the extracellular matrices comprised of collagen gel and Matrigel, were
      transplanted into nude mice. Proliferation was measured in vivo by BrdU labeling
      followed by immunostaining of sections from recovered gels in response to an
      altered hormonal environment of the host animal. The host animal was mated to
      undergo pregnancy and the complex hormonal environment of the host animal
      pregnancy stimulated growth of transplanted human cells. This effect increased
      with progression of pregnancy and reached the maximum during late pregnancy prior
      to parturition. In order to determine whether additional stimulation could be
      achieved, the transplanted human cells were exposed to a second cycle of host
      mouse pregnancy by immediately mating the animal after parturition. This
      additional exposure of host mouse pregnancy did not result in further increase of
      proliferation. The effect of hCG administration on transplanted human cells was
      also tested, since hCG level is highest during the first trimester of human
      pregnancy and coincides with the maximal breast cell proliferation.
      Administration of hCG alone stimulated proliferation of human cells in a dose
      dependent manner, and could further enhance stimulation achieved with estrogen.
      The host mouse mammary gland also responded to hCG treatment resulting in
      increased branching and lobulo-alveolar development. However, the hCG effect on
      both human and mouse cells was dependent on intact ovary since the stimulation
      did not occur in ovariectomized animals. Although hCG receptor transcripts were
      detected in human breast epithelial cells, raising the possibility of a direct
      mitogenic action, the hCG effect observed in this study may have been mediated
      via the ovary by increased secretion of ovarian steroids. In summary, using our
      in vivo nude mice system, the proliferation of normal human breast epithelial
      cells could be stimulated by host mouse pregnancy and by administration of hCG.

PMID- 11241181
TI  - The effects of lipopolysaccharide and interleukins-1alpha, -2 and -6 on oxytocin
      receptor expression and prostaglandin production in bovine endometrium.
AB  - Up-regulation of endometrial oxytocin receptor (OTR) expression followed by an
      increase in pulsatile endometrial prostaglandin (PG) F(2alpha) secretion causes
      luteolysis in cattle. Inhibition of luteolysis is essential for the maternal
      recognition of pregnancy but also occurs in association with endometritis. The
      factors regulating OTR expression at this time are unclear. The OTR gene promoter
      region contains binding elements for acute phase proteins but their function has
      not been established. This study investigated the effects of various cytokines on
      OTR expression and on PGF(2alpha) and PGE(2) production in explant cultures of
      bovine endometrium. Endometrium was collected in the late luteal phase (mean day
      of cycle 15.4+/-0.50) or early luteolysis (mean day of cycle 16.4+/-0.24) as
      determined by the initial concentration of endometrial OTR. Explants were treated
      for 48 h with: (i) lipopolysaccharide (LPS) and/or dexamethasone (DEX), (ii)
      ovine interferon-tau (oIFN-tau), or (iii) human recombinant interleukin (IL)
      1alpha, -2 or -6. OTR mRNA was then measured in the explants by in situ
      hybridisation and the medium was collected for measurement of PGF(2alpha) and
      PGE(2) by RIA. LPS treatment stimulated production of PGF(2alpha), whereas DEX
      either alone or in combination with LPS was inhibitory to both PGF(2alpha) and
      PGE(2). Neither of these treatments altered OTR mRNA expression. oIFN-tau reduced
      OTR mRNA expression but stimulated production of both PGF(2alpha) and PGE(2). In
      endometrial samples collected in the late luteal phase, IL-1alpha, -2 and -6 all
      inhibited OTR mRNA expression, but IL-1alpha and -2 both stimulated PGF(2alpha)
      production. In contrast, when endometrium was collected in early luteolysis, none
      of the interleukins altered OTR expression or caused a significant stimulation of
      PGF(2alpha) production but IL-2 increased PGE(2). Neither IL-1alpha nor -2
      altered OTR promoter activity in Chinese hamster ovary cells transfected with a
      bovine OTR promoter/chloramphenicol acetyl transferase reporter gene construct.
      In conclusion, the action of interleukins on both OTR mRNA expression and
      endometrial prostaglandin production alters around luteolysis. Pro-inflammatory
      interleukins suppress OTR expression in the late luteal phase, while LPS
      stimulates PGF(2alpha) without altering OTR mRNA expression. IL-I and -2 and LPS
      are therefore unlikely to initiate luteolysis but may cause raised production of
      PGF(2alpha) during uterine infection.

PMID- 11241182
TI  - Endocrine regulation of G-protein subunit production in an animal model of type 2
      diabetes mellitus.
AB  - Adipocyte beta-adrenergic sensitivity is compromised in animal models of obesity
      and type 2 diabetes. Although changes in the membrane concentrations of G-protein
      alpha subunits (Galpha) have been implicated, it remains to be determined how
      these changes are affected by insulin resistance in the different animal models.
      Because previous studies used young animals, we measured the concentrations of
      Galpha and Gbeta subunits in epididymal fat from aged (48 weeks old) db/db mice
      and from their lean littermates to more closely reproduce the model of type 2
      diabetes mellitus. Levels of immunoreactive Galphas, Galphai(1/2), Galphao and
      Galphaq/11 were all significantly greater in adipocyte membranes from the db/db
      mice than in membranes from their lean non-diabetic littermate controls. Levels
      of Galphai(1) and Galphai(2) were also individually determined and although they
      appeared to be slightly higher in db/db membranes, these differences were not
      significant. Although the levels of both Galphas isoforms were elevated, levels
      of the 42 and 46 kDa proteins rose by approximately 42% and 20% respectively,
      indicating differential protein processing of Galphas. By contrast, levels of
      Galphai3 were similar in the two groups. The levels of common Gbeta and Gbeta2
      were also elevated in db/db mice, whereas Gbeta1 and Gbeta4 levels were not
      different. To determine whether these changes were due to insulin resistance per
      se or to elevated glucocorticoid production, G-protein subunit levels were
      quantified in whole cell lysates from 3T3-L1 adipocytes that were stimulated with
      different concentrations of either insulin or corticosterone. Although none of
      the subunit levels was affected by insulin, the levels of both Galphas isoforms
      were increased equally by corticosterone in a concentration-dependent manner.
      Since glucocorticoids are known regulators of Galphas gene expression in many
      cell types and in adipocytes from diabetic rodents, the results presented herein
      appear to more accurately reflect diabetic pathophysiology than do those of
      previous studies which report a decrease in Galphas levels. Taken together, these
      results indicate that most of the selective changes in G-protein subunit
      production in adipocytes from this animal model of type 2 diabetes may not be due
      to diminished insulin sensitivity, but may be due to other endocrine or metabolic
      abnormalities associated with the diabetic phenotype.

PMID- 11241183
TI  - NCX1 Na/Ca exchanger splice variants in pancreatic islet cells.
AB  - In the rat pancreatic beta-cell, Na/Ca exchange displays a quite high capacity.
      The cell is equipped with two alternatively spliced Na/Ca exchanger-1 (NCX1)
      isoforms, namely NCX1.3 and NCX1.7. To examine the existence of a possible
      functional difference between these splice variants, they were cloned, together
      with the heart variant NCX1.1, and expressed in human embryonic kidney-293
      (HEK293) and Chinese hamster ovary (CHO) cells. In these two systems, the three
      splice variants showed a comparable level of intracellular Na+ (Na+(i))-dependent
      extracellular Ca2+(Ca2+(o)) uptake. Different levels of NCX1.3 and NCX1.7
      transcripts were found in four rodent species, together with a marked
      interspecies difference in Na/Ca exchange activity. Three additional splice
      variants were found (NCX1.2, NCX1.9 and NCX1.13) in guinea-pigs, hamsters and
      mice, again in different proportions. Our data provide evidence for the activity
      of the three NCX1 splice variants. They also show the existence of a differential
      and species-specific transcription pattern of NCX1 gene products in pancreatic
      islet cells.

PMID- 11241184
TI  - Identification of avian alpha-melanocyte-stimulating hormone in the eye: temporal
      and spatial regulation of expression in the developing chicken.
AB  - The presence and possible physiological roles of alpha-melanocyte-stimulating
      hormone (alpha-MSH) in the peripheral tissues of birds have not been established.
      By a combination of RT-PCR, immunocytochemistry and in situ hybridization, we
      have examined alpha-MSH expression in the eye of the chicken during development.
      In the 1-day-old chick, alpha-MSH was expressed in the retinal pigment epithelial
      (RPE) cells, and also at a lower level in the cone cells. The melanocortin
      receptor subtypes, CMC1, CMC4 and CMC5, were expressed in the layers of the
      choroid and the neural retina, but not in the RPE cells. It is probable that the
      RPE cells secrete alpha-MSH to exert paracrine effects on the choroid and neural
      retina. During embryonic development, alpha-MSH immunoreactivity in the RPE cells
      was initially detected at embryonic day 10, and increased in intensity as
      development proceeded. No cone cells were stained with anti-alpha-MSH antiserum
      in any of the embryonic stages tested. The immunoreactivities for two prohormone
      convertases, PC1 and PC2, were co-localized to the RPE cells with a pattern of
      staining similar to that of alpha-MSH. Despite containing alpha-MSH
      immunoreactivity, the RPE cells in 1-day-old chicks expressed no immunoreactivity
      for the endoproteases. Furthermore, in a 3-day-old chick, pro-opiomelanocortin
      mRNA was detectable by in situ hybridization only in the photoreceptor layer and
      not in the RPE cells. These results suggest that the RPE cells and the cone cells
      are intraocular sources of alpha-MSH in the embryonic and postnatal life of the
      chicken respectively. Embryonic expression of alpha-MSH in the RPE cells implies
      a possible role for the peptide in ocular development.

PMID- 11241185
TI  - Origin of anthropoidea: dental evidence and recognition of early anthropoids in
      the fossil record, with comments on the Asian anthropoid radiation.
AB  - Among the earliest fossil anthropoid primates known are Catopithecus browni,
      Serapia eocaena, Arsinoea kallimos, and Proteopithecus sylviae, from the late
      Eocene quarry L-41, Fayum Depression, Egypt. Two of these taxa, C. browni and S.
      eocaena, may be the oldest known members of the Propliopithecidae and
      Parapithecidae, respectively, while A. kallimos and P. sylviae are archaic
      anthropoids of less certain familial affiliation. Dental features of C. browni,
      S. eocaena, A. kallimos, and P. sylviae are compared with those of younger
      propliopithecids and parapithecids from the Fayum in order to determine the
      morphocline polarities of dental features among these early anthropoids. From
      this, a basal African anthropoid dental morphotype is constructed. Among the
      features of this morphotype are: dental formula of 2.1.3.3; incisors
      subvertically implanted and somewhat spatulate; p2 as large as p3, both lacking
      paraconids; p4 weakly obliquely oriented but not exodaenodont; all lower molars
      with small paraconids present; upper anterior premolars lacking protocone; upper
      molars with small, cingular hypocones, all cheek teeth nonbunodont; and canines
      projecting but not necessarily sexually dimorphic. Comparisons are made between
      this African anthropoid morphotype and two of the best-represented proposed basal
      anthropoids, Eosimias and Djebelemur, with the result that neither appears to be
      a good candidate to have been ancestral to the African anthropoids. Other
      possible basal simians such as Algeripithecus, Tabelia, and Biretia also are
      evaluated but are too poorly known for adequate analysis. The larger-bodied Asian
      primates Pondaungia, Amphipithecus, and Siamopithecus also are not likely
      ancestors for African anthropoids, but like Eosimias they may share a common
      ancestry. Despite many recent claims of an Asian origin for anthropoids, the
      evidence remains far from compelling. The true origins of Anthropoidea remain
      obscure.

PMID- 11241186
TI  - Teeth, brains, and primate life histories.
AB  - This paper explores the correlates of variation in dental development across the
      order Primates. We are particularly interested in how 1) dental precocity
      (percentage of total postcanine primary and secondary teeth that have erupted at
      selected absolute ages and life cycle stages) and 2) dental endowment at weaning
      (percentage of adult postcanine occlusal area that is present at weaning) are
      related to variation in body or brain size and diet in primates. We ask whether
      folivores have more accelerated dental schedules than do like-sized frugivores,
      and if so, to what extent this is part and parcel of a general pattern of
      acceleration of life histories in more folivorous taxa. What is the adaptive
      significance of variation in dental eruption schedules across the order Primates?
      We show that folivorous primate species tend to exhibit more rapid dental
      development (on an absolute scale) than comparably sized frugivores, and their
      dental development tends to be more advanced at weaning. Our data affirm an
      important role for brain (rather than body) size as a predictor of both absolute
      and relative dental development. Tests of alternative dietary hypotheses offer
      the strongest support for the foraging independence and food processing
      hypotheses.

PMID- 11241187
TI  - Analysis of dentition of a living wild population of ring-tailed lemurs (Lemur
      catta) from Beza Mahafaly, Madagascar.
AB  - Detailed descriptions of the dentition of many strepsirhine primate taxa are
      rare, despite their importance in understanding primate evolutionary biology.
      While several researchers have provided detailed morphological descriptions of
      ring-tailed lemur dentition (e.g., Schwartz and Tattersall [1985] Am. Mus. Nat.
      Hist. Anthropol. Pap. 60:1-100; Tattersall and Schwartz [1991] Am. Mus. Nat.
      Hist. Anthropol. Pap. 69:2-18), there are few studies (e.g., Eaglen [1986] Am. J.
      Phys. Anthropol. 71:185-201) that present quantitative data on the dentition of
      this species. Furthermore, prior analyses were based on museum specimens from
      various populations and locations. We present here quantitative and morphological
      data on the dentition of a population of wild Lemur catta from Beza Mahafaly
      Special Reserve, Madagascar. Measurements were made on dental casts (n = 39)
      taken from living members of this L. catta population. Our analysis indicates
      that no significant (P > 0.05) sexual dimorphism exists for the 30 dental
      measurements collected. These data support the generalizations (e.g., Plavcan and
      van Schaik [1994] Evol. Anthropol. 2:208-214; Kappeler [1996] J. Evol. Biol. 9:43
      65) that little sexual dimorphism in dentition exists among Malagasy
      strepsirhines. In addition, the overall patterns of metric variation in this
      sample compare favorably with patterns seen among other primates, e.g., premolar
      measurements varying more than molars (e.g., Gingerich [1974] J. Paleontol.
      48:895-903). However, there is a degree of intraspecific morphological variation
      indicated, with one of the morphological traits discussed in other studies as
      being species-specific for L. catta (absence of P(4) metaconids) observed to vary
      between specimens. Because the patterns of variation seen in this sample are from
      a known breeding population, the data presented here provide an important
      reference for interpreting and understanding the fossil record.

PMID- 11241188
TI  - Prefrontal cortex in humans and apes: a comparative study of area 10.
AB  - Area 10 is one of the cortical areas of the frontal lobe involved in higher
      cognitive functions such as the undertaking of initiatives and the planning of
      future actions. It is known to form the frontal pole of the macaque and human
      brain, but its presence and organization in the great and lesser apes remain
      unclear. It is here documented that area 10 also forms the frontal pole of
      chimpanzee, bonobo, orangutan, and gibbon brains. Imaging techniques and
      stereological tools are used to characterize this area across species and provide
      preliminary estimates of its absolute and relative size. Area 10 has similar
      cytoarchitectonic features in the hominoid brain, but aspects of its organization
      vary slightly across species, including the relative width of its cortical layers
      and the space available for connections. The cortex forming the frontal pole of
      the gorilla appears highly specialized, while area 10 in the gibbon occupies only
      the orbital sector of the frontal pole. Area 10 in the human brain is larger
      relative to the rest of the brain than it is in the apes, and its supragranular
      layers have more space available for connections with other higher-order
      association areas. This suggests that the neural substrates supporting cognitive
      functions associated with this part of the cortex enlarged and became specialized
      during hominid evolution.

PMID- 11241189
TI  - Coca chewing in prehistoric coastal Peru: dental evidence.
AB  - In this study, we describe the dental health of four prehistoric human
      populations from the southern coast of Peru, an area in which independent
      archaeological evidence suggests that the practice of coca-leaf chewing was
      relatively common. A repeated pattern of cervical-root caries accompanying root
      exposure was found on the buccal surfaces of the posterior dentition, coinciding
      with the typical placement of coca quids during mastication. To further examine
      the association between caries patterning and coca chewing, caries site
      characteristics of molar teeth were utilized as indicators for estimating the
      likelihood of coca chewing for adults within each of the study samples.
      Likelihood estimates were then compared with results of a test for coca use
      derived from hair samples from the same individuals. The hair and dental studies
      exhibited an 85.7% agreement. Thus, we have demonstrated the validity of a hard
      tissue technique for identifying the presence of habitual coca-leaf chewing in
      ancient human remains, which is useful in archaeological contexts where hair is
      not preserved. These data can be used to explore the distribution of coca chewing
      in prehistoric times. Simultaneously, we document the dental health associated
      with this traditional Andean cultural practice.

PMID- 11241191
TI  - Brief communication: paleoanthropology and the population genetics of ancient
      genes.
AB  - The Mezmaiskaya cave mtDNA is similar in many ways to the Feldhofer cave
      Neandertal sequence and the more recently obtained Vindija cave sequence. If we
      accept the contention that the Mezmaiskaya cave specimen is a Neandertal infant,
      its mtDNA provides no new information about the fate of the European Neandertals.
      However, there is reason to believe that the Mezmaiskaya cave infant is not a
      Neandertal, and this places its importance in another light, because it delimits
      the possible hypotheses of Neandertal and recent human genetic relationships. One
      possibility is a that the pattern found in ancient mtDNA results from the
      replacement of an isolated gene pool (Neandertals) by one of its contemporaries
      (modern humans). A second possibility is natural selection expressed as the
      substitution of an advantageous mtDNA variant within a single large species,
      including both Neandertals and modern humans. The geologic, archaeological, and
      dating evidence shows the Mezmaiskaya cave infant to be a burial from a level
      even more recent than the Upper Paleolithic preserved at the site, and its
      anatomy does not contradict the assessment that the Mezmaiskaya cave infant is
      not a Neandertal. Therefore, the second pattern can be favored over the first.

PMID- 11241190
TI  - Physical activity and subsistence pattern of the Huli, a Papua New Guinea
      Highland population.
AB  - Several studies on human energetics have been conducted in developed and
      developing countries, but very few simultaneously measured time use and energy
      expenditure. Only a few quantitatively compared subsistence patterns between
      rural and urban dwellers of an identical population. Here we present the daily
      physical activity level (PAL), physical exertion, time, and energy expenditure in
      contrasting subsistence/occupational activities of Papua New Guinea Highlanders,
      comparing 27 rural villagers (15 men, 12 women) who maintained traditional
      subsistence agriculture, with 29 urban migrants (14 men, 15 women) who engaged in
      cash-earning work. A large sex inequality in the division of labor was noted
      between rural males and females, but not among urban dwellers. Rural-urban
      comparison indicated sex differences in urbanization. For urban men, the
      reduction of physical exertion level during work, from energy-consuming
      agricultural work to sedentary cash-earning work, together with significantly
      extended work time (by 261 min/day, P < 0.001), led to an increase in work energy
      expenditure (15-29% of PAL). In contrast, urban women who spent almost equal time
      at work relative to rural women showed a lower energy expenditure (18% compared
      to 26% of PAL). The associations with urbanization included a gain in body weight
      (by 6.4 kg for either sex) and reduced PAL (by 7%, not significant in men; 13%, P
      < 0.01 in women). Further research is needed to elucidate the effects of
      urbanization on time use, energy expenditure, and PAL, by comparing rural
      residents with urban migrants in the same population.

PMID- 11241192
TI  - Distribution of neuropeptide Y-like immunoreactivity in the brain of the
      Senegalese sole (Solea senegalensis).
AB  - We present the results of an immunohistochemical study aimed at localizing the
      neuropeptide Y (NPY) in the brain of the Senegalese sole, Solea senegalensis,
      using an antiserum raised against porcine NPY and the streptavidin-biotin
      peroxidase method. In this species, we have identified immunoreactive cells in
      the ventral and dorsal telencephalon, caudal preoptic area, ventrocaudal
      hypothalamus, optic tectum, torus longitudinalis, synencephalon and isthmic
      region. NPY-immunoreactive fibers were profusely distributed throughout the
      brain, also reaching the adenohypophysis. The extensive distribution of NPY
      suggests an important role for this neuropeptide in a variety of physiological
      processes, including the neuroendocrine control of adenohypophyseal functions.
      Our results are compared with those obtained in other teleosts and discussed in
      relation to putative functions of NPY in the control of metabolism and
      reproduction in the Senegalese sole.

PMID- 11241193
TI  - New insights into critical events of avian gastrulation.
AB  - The formation and progression of the primitive streak are key events of avian
      gastrulation. We examine these processes in detail, using various morphological
      approaches. We show that formation of the primitive streak occurs locally at the
      caudal midline of the area pellucida, as cells in the caudal midline undergo an
      epithelial-to-mesenchymal transformation, and that extensive migration of
      delaminated cells arising from more rostral or peripheral areas of the blastoderm
      is not involved in streak formation. Instead, such delamination occurs earlier
      and is restricted to the process of hypoblast formation. Moreover, we provide
      evidence that progression of the primitive streak involves two processes:
      convergent-extension movements within the streak per se, and progressive
      delamination of midline epiblast cells in a caudal-to-rostral sequence. We have
      identified a subpopulation of primitive-streak cells located at its dorsal
      midline surface that undergoes extensive rostral displacement concomitant with
      streak progression. The fact that these cells are located only dorsally and do
      not elongate ventrally as do adjacent ingressing cells, suggests that these cells
      retain their residency within the primitive streak, at least until regression of
      the primitive streak occurs. Finally, by following labeled cells over time we
      establish the timing of movement of epiblast cells toward and into the primitive
      streak, providing direct evidence that cell-cell intercalation occurs within the
      primitive streak during its progression. Collectively, our results provide new
      insight into complex and central events of avian gastrulation.

PMID- 11241195
TI  - Ontogeny of galanin-immunoreactive elements in chicken embryo autonomic nervous
      system.
AB  - To elucidate the main ontogenetic steps of galanin immunoreactivity within the
      extrinsic nerve supply of the alimentary tract, we undertook an
      immunohistochemical study of chicken embryo specimens. Fluorescence and
      streptavidin-biotin-peroxidase protocols were combined, using a galanin
      polyclonal antiserum, on transverse serial sections obtained from chicken embryos
      from embryonic Day 3 (E3) to hatching, and from 9-day-old newborn chicks. Galanin
      immunoreactive cells were first detected at E3.5 within the pharyngeal pouch
      region, the nodose ganglion, the primary sympathetic chain, primitive splanchnic
      branches and the caudal portion of the Remak ganglion. At E5.5 galanin
      immunoreactive cells and fibers appeared in the secondary (paravertebral)
      sympathetic chain, splanchnic nerves, peri- and preaortic plexuses, adrenal gland
      anlage and visceral nerves. Galanin-immunoreactive cells also lay scattered along
      the vagus nerve, and in the intermediate zone of the thoracolumbar spinal cord.
      At E18, galanin-immunoreactive cells and fibers were found along the entire Remak
      ganglion and around the gastrointestinal blood vessels. In post-hatching-9-day
      old chicks, the para- and prevertebral ganglia, but not the intermediate zone of
      the spinal cord, contained galanin-immunoreactive cells. Data indicate the
      presence of a consistent "galaninergic" nerve system supplying the chick
      embryonal gut wall. Whether this system has growth or differentiating role
      remains to be demonstrated. Its presence and distribution pattern in the later
      stages clearly support its well known role as a visceral neuromodulator of gut
      function.

PMID- 11241194
TI  - Morphological analysis of the postnatally developing marsupial lung: The quokka
      wallaby.
AB  - We investigated the events that take place during the postnatal morphogenesis of
      the lung of the quokka wallaby, Setonix brachyurus, using the light microscope
      and both the scanning and transmission electron microscopes. The lung of term,
      newborn babies (joeys) at 3-days of postnatal life was at late canalicular stage
      and comprised large airways and tubules separated by thick mesenchymal
      interstitium. The tubules were lined by a low cuboidal epithelium but had few
      portions with true gas exchange barrier where capillaries came into close contact
      with squamous type of epithelium. By the fifth day postpartum, the lung entered
      the early saccular stage characterised by large air sacs, thinner septa, a better
      developed double capillary system and conversion of the cuboidal epithelium into
      a squamous one of type I cells interrupted by groups of cuboidal type II cells
      with lamellar bodies. Transitory respiratory bronchioles were recognisable toward
      the end of this stage. Formation of secondary septa started by Day 15, dividing
      the saccules into several generations of smaller air spaces. There were
      alternating and concurrent periods of tissue proliferation and air space
      expansion, followed by septal thinning. Alveolization started from about 125 days
      postpartum when the first burst of small sized air spaces bounded by septa with a
      single capillary layer were encountered. By Day 180 the process of alveolization
      was completed with only occasional septa showing a double capillary system and by
      Day 210 postnatally, the lung resembled that of an adult. For the first time in a
      mammal, the canalicular stage was encountered postnatally during lung
      development.

PMID- 11241196
TI  - Development of the follicle-associated epithelium and the secretory dendritic
      cell in the bursa of fabricius of the guinea fowl (Numida meleagris) studied by
      novel monoclonal antibodies.
AB  - Two stromal elements, follicle-associated epithelium and secretory dendritic
      cells of the bursa of Fabricius were studied by light microscopy and two novel
      MAbs, that were produced against splenic cell suspensions of guinea fowls. Both
      antigens recognized by these MAbs, designated GIIF3 and NIC2, are localized in
      the cytoplasm of the stromal cells, and their molecular weights are 50 and 30 kD,
      respectively. During embryogenesis the GIIF3 and NIC2 cells emerge in the
      mesenchyme of the folds before follicle formation. The GIIF3 and the NIC2
      positive cells accumulate under the surface epithelium of the plicae and migrate
      into the epithelium, that precedes the bud-formation. From the bud, the GIIF3
      positive cells migrate up to the luminal surface, and they transform to distinct,
      highly polarized follicle-associated epithelial cells. Single GIIF3-positive
      cells are also present in the interfollicular epithelium. The NIC2 MAb recognized
      mesenchymal cells harbor in the lymphoepithelial compartment of the folliculus,
      and they elaborate cytoplasmic granules. Around Day 20 of embryogenesis large
      amount of NIC2-positive substance appear extracellularly in the medulla and
      around it. This period well correlates with the starting up of the bursal
      functions; clonal expansion of B cells, and generation of immune repertoire.
      After hatching the NIC2 stainability diminishes, and it is restricted to the
      medullary bursal secretory dendritic cells. The NIC2-positive, possibly elderly
      bursal secretory dendritic cells, are capable for migration into the follicle
      associated epithelium. In eight-day old birds some cells of the follicle
      associated epithelium reveals temporary NIC2 positivity, that may prove the
      transport of the follicle-associated epithelial cells into luminal direction. By
      12 weeks of age the presence of NIC2-positive substance in the intercellular
      space of the FAE, rather than in the cells of FAE may indicate the termination of
      the transport of secretory substance. In conclusion, two types of mesenchymal
      cells enter the surface epithelium of the bursal folds. The GIIF3-positive cells
      appear on the luminal surface of the follicles and occupy the place of the
      follicle-associated epithelial cells. The NIC2-positive cells become secretory in
      nature and differentiate to bursal secretory dendritic cells. The follicle
      formation possibly, requires the joint presence of both GIIF3 and NIC2 cells in
      the epithelium.

PMID- 11241197
TI  - Length changes in the human masseter muscle after jaw movement.
AB  - The human masseter is a multilayered, complex muscle contributing to jaw motion.
      Because variations in stretch may cause muscle fibers to function over different
      portions of their length-tension curves, the aim of this study was to determine
      how parts of the masseter lengthen or shorten during voluntary jaw movements made
      by living subjects. Magnetic resonance (MR) imaging and optically-based jaw
      tracking were used to measure muscle-insertion positions for four parts of the
      muscle with six degrees of freedom (DOF), before and after maximum-opening, jaw
      protrusion and laterotrusion in four adult males. Muscle part lengths and
      intramuscular tendon lengths were calculated, and these data, with fiber-tendon
      ratios published previously, were used to estimate putative changes in fiber
      length. During maximum jaw-opening, the largest increases in muscle length (34
      83%) occurred in the medial part of the deep masseter, whereas the smallest
      changes occurred in the posterior-most, superficial masseter (2-19%). Smaller
      changes were found during movement to the ipsilateral side, than during
      protrusion and movement to the contralateral side. On maximum opening, putative
      fibers in the deep masseter lengthened up to 83%, whereas those of the
      superficial masseter stretched up to 72%. The masseter muscle does not stretch
      uniformly for major jaw movement. Jaw motion to the ipsilateral side causes
      little length change in any part, and the effect of tendon-stretch on estimated
      fiber lengths is not substantial. The stretch that occurs infers there are task
      related changes in the active and passive tensions produced by different muscle
      regions.

PMID- 11241198
TI  - Muscle length affects the architecture and pattern of innervation differently in
      leg muscles of mouse, guinea pig, and rabbit compared to those of human and
      monkey muscles.
AB  - The innervation pattern and fascicular anatomy of muscles of different lengths in
      mouse, guinea pig, rabbit, macaque monkey and human legs were analyzed.
      Neuromuscular junctions, muscle tendon junctions and ends of intrafascicularly
      terminating fibers were stained for acetylcholinesterase, and fascicle lengths
      measured. A high correlation between increasing fascicle length and increasing
      number of neuromuscular junctions was found, with non-primate (mouse, guinea pig,
      rabbit) and primate (macaque monkey, human) muscles forming two discrete groups.
      In non-primates, muscles with a single endplate band, fascicles were always
      shorter than 35 mm, fixing the limit of fiber length served by one neuromuscular
      junction. Muscles with fascicles longer than this had multiple discrete bands of
      motor endplates crossing their width at regular intervals. An increase in muscle
      length across or within species corresponded to an equivalent, standard increase
      of 10-12 mm fascicle length per motor endplate band. All human and monkey leg
      muscles, with the exception of gracilis and sartorius, were singly innervated and
      all muscle fibers ran the full distance from tendon to tendon. Singly innervated
      primate muscle fibers were up to 140 mm long whereas the mean distance between
      endplate bands in the two multiply innervated muscles was also considerably
      greater than in non-primates. These data indicate that allometric effects of
      increasing fascicle length, are distinct in common laboratory animals and two
      primates, when architecture and pattern of innervation are compared.

PMID- 11241199
TI  - Apoptosis during coronary artery orifice development in the chick embryo.
AB  - Previous studies regarding the development of proximal segments of the coronary
      arteries in the chick have demonstrated that these vessels do not develop as
      angiogenic outgrowths from the aorta. Rather, the proximal segments of the
      coronary arteries arise from a peritruncal capillary plexus in the epicardium
      that coalesces around the aortic and pulmonary outflow tracts. Vessels from the
      peritruncal plexus grow toward and attach to the aorta at about Hamburger and
      Hamilton (HH) Stage 32 to establish the definitive coronary circulation.
      Currently, little is known about the process by which patent connections are
      established between these peritruncal vessels and the aorta. The hypothesis that
      apoptosis is involved in the formation of the coronary artery orifices was tested
      in the present study. Aortic and periaortic tissue from HH 29-35 chick embryos
      was examined using routine light and electron microscopy and TUNEL assays.
      Apoptotic cells were observed in close spatial and temporal association with the
      invasion of peritruncal vessels into the aorta (HH 29-31), the initial formation
      of coronary orifices (HH 32-33), and the further development of the definitive
      coronary arteries and orifices (HH 34-35). Whereas the origin of these apoptotic
      cells and the specific factors regulating their death remain unknown, the results
      of the present study strongly correlate apoptosis with the formation of proximal
      coronary arteries and their orifices. Our findings suggest avenues for further
      research and indicate that factors involved in regulating apoptosis should be
      included in future models of coronary artery development.

PMID- 11241200
TI  - Embryonic mouse submandibular salivary gland morphogenesis and the TNF/TNF-R1
      signal transduction pathway.
AB  - TNF is a pleiotropic cytokine that modulates cell proliferation and apoptosis.
      The objective of the present study was to investigate the possible function(s) of
      the TNF/TNF-R1 signaling pathway in embryonic mouse submandibular salivary gland
      (SMG) morphogenesis. After characterizing in vivo mRNA and protein expression of
      various constituents of this pathway, we utilized in vitro experiments to
      investigate the phenotypic outcomes of enhanced and deficient ligand. The results
      of these experiments indicate that the TNF/TNF-R1 signal transduction pathway
      plays an important role in balancing cell proliferation and apoptosis during SMG
      duct and presumptive acini formation.

PMID- 11241201
TI  - Intervertebral disc disorganisation and its relationship to age adjusted
      vertebral body morphometry and vertebral bone architecture.
AB  - Vertebral deformity, intervertebral disc disorganisation, and change to vertebral
      bone architecture are morphological features that are associated with low back
      pain. The purpose of this study was to examine the influence of the morphological
      disorganisation of the intervertebral disc on vertebral body shape indices and
      vertebral cancellous bone architecture. Lumbar spines, T12-S1, were collected
      from 27 cadavers. The motion segments T12-L1, L2-L3 and L4-L5 were selected for
      the study. There were 8 females aged 35-94 years and 19 males aged 20-90 years.
      An intervertebral disc grade signifying the severity of disc disorganisation was
      assigned to each disc using the macroscopic disc grading criteria of Hansson and
      Roos (Spine, 1981; 6:147-153.). Vertebral shape indices and vertebral body bone
      histomorphometric analyses were performed on the vertebral bodies. Where
      appropriate, data were age adjusted and the influence of morphological disc
      disorganisation on vertebral body deformity and cancellous bone architecture
      analysed. Increased vertebral body axial area and the ratio of vertebral body
      axial area to sagittal area were associated with an increase in vertebral
      deformity and disc disorganisation. This suggests that vertebral deformity that
      remains clinically silent in the general population is influenced by
      intervertebral disc disorganisation. Vertebral cancellous bone architecture
      undergoes change associated with increased disc disorganisation, consistent with
      increased vertebral deformity. Vertebral bodies adjacent to degenerate discs
      (Grade 4) showed increased BV/TV and Tb.Th and decreased BS/BV. This shows that
      disc disorganisation may modulate vertebral cancellous bone architecture such
      that it protects against age-related bone changes. In addition, vertebral body
      wedging and concavity are associated with smaller vertebral body size and
      vertebral body compression is associated with larger vertebral body size and
      compromised cancellous bone architecture.

PMID- 11241204
TI  - Edward H. Bloch, M.D., Ph.D.: Pioneer in the microscopic study of and the
      microcirculation of living tissues and organs.

PMID- 11241205
TI  - It's ethical, but is it legal? Teaching ethics and law in the medical school
      curriculum.
AB  - While Western medical ethics has ancient roots in the teachings of Hippocrates,
      its standing in the undergraduate medical curriculum is a distinctly modern
      development. Today, all of the 127 accredited U.S. medical schools offer formal
      biomedical ethics instruction, and nearly all offer instruction in the related
      discipline of health law. This article describes how biomedical ethics and health
      law are taught at the University of Iowa College of Medicine, one of 12 medical
      schools that offers separate required courses in both ethics and law. Often
      ethics and law overlap; often, to act ethically is to act legally. But medical
      students and practicing physicians also regularly confront dilemmas that pose the
      question, "It's ethical, but is it legal?" This article discusses the goals,
      methods, and core themes of teaching issues at the intersection of medicine,
      ethics, and law, and how the approach to this instruction is designed to offer
      students a tool kit to begin to deal effectively with these complex issues in
      professional life. Anat Rec (New Anat) 265:5-9, 2001.

PMID- 11241206
TI  - Comparison of a virtual microscope laboratory to a regular microscope laboratory
      for teaching histology.
AB  - Emerging technology now exists to digitize a gigabyte of information from a glass
      slide, save it in a highly compressed file format, and deliver it over the web.
      By accessing these images with a standard web browser and viewer plug-in, a
      computer can emulate a real microscope and glass slide. Using this new
      technology, the immediate aims of our project were to digitize the glass slides
      from urinary tract, male genital, and endocrine units and implement them in the
      Spring 2000 Histology course at the University of Iowa, and to carry out a
      formative evaluation of the virtual slides of these three units in a side-by-side
      comparison with the regular microscope laboratory. The methods and results of
      this paper will describe the technology employed to create the virtual slides,
      and the formative evaluation carried out in the course. Anat Rec (New Anat)
      265:10-14, 2001.

PMID- 11241207
TI  - Anatomical appraisal of the skulls and teeth associated with the family of Tsar
      Nicolay Romanov.
AB  - This article describes the identification of skeletal remains attributed to the
      family of Tsar Nicolay Romanov and other persons buried together at a site near
      present-day Ekaterinburg, Russia. Detailed descriptions are given regarding the
      objective methods of craniofacial and odontological identification that were
      used. Employing computer-assisted photographic superimposition techniques and
      statistical analysis of morphologic and other characteristics of the specimens,
      this study identifies with a high likelihood of certainty the remains of the
      Tsar, his wife, three of his four daughters, and four household assistants. Very
      strong evidence is presented that the Tsar's daughter Anastasia was killed in
      1918. This study demonstrates the effectiveness of the methods and
      trustworthiness of the results, as well as the prospects of future application of
      the methods for the identification of skeletonized human remains. Anat Rec (New
      Anat) 265:15-32, 2001.

PMID- 11241210
TI  - Modulation of membrane curvature by peptides.
AB  - The fusion of two stable bilayers likely proceeds through intermediates in which
      the membrane acquires curvature. The insertion of peptides into the membrane will
      affect its curvature tendency. Studies with a number of small viral fusion
      peptides indicate that these peptides promote negative curvature at low
      concentration. This is in accord with the curvature requirements to initiate
      membrane fusion according to the stalk-pore model. Although a characteristic of
      fusion peptides, the promotion of negative curvature is only one of several
      mechanisms by which fusion proteins accelerate the rate of fusion. In addition,
      the fusion peptide itself, as well as other regions in the viral fusion protein,
      facilitates membrane fusion by mechanisms that are largely independent of
      curvature. Leakage of the internal aqueous contents of liposomes is another
      manifestation of the alteration of membrane properties. Peptides exhibit quite
      different relative potencies between fusion and leakage that is determined by the
      structure and mode of insertion of the peptide into the membrane.

PMID- 11241211
TI  - Conformational and orientation studies of artificial ion channels incorporated
      into lipid bilayers.
AB  - The conformational and orientation studies in lipid bilayers of 21 amino acid
      peptides bearing six crown ethers are reported. The compounds were designed to
      form artificial ion channels by stacking the crown rings, and were shown to be
      functional in bilayer membranes. We used Fourier transform infrared spectroscopy
      and CD spectropolarimetry to study the conformation of the peptides in solution
      and in lipid bilayers. These studies revealed that hexacrown peptides retain
      their alpha-helical conformation when incorporated in a lipid bilayer
      environment. Attenuated total reflectance spectroscopy was used to investigate
      the orientation of the peptides in a lipid bilayer. Results demonstrated that the
      peptides are not oriented at a fixed angle in membrane, but rather are in
      incorporation equilibrium between an active state parallel to the lipid chain and
      an inactive state adsorbed at the surface of the bilayer. From these results, we
      propose a model for the channel activity and the gating mechanism of these
      hexacrown peptides in bilayer membranes.

PMID- 11241212
TI  - Attenuated total reflection IR spectroscopy as a tool to investigate the
      structure, orientation and tertiary structure changes in peptides and membrane
      proteins.
AB  - During the last few years, attenuated total reflection Fourier transform infrared
      spectroscopy (ATR-FTIR) has become one of the most powerful methods to determine
      the structure of biological materials and in particular of components of
      biological membranes, like proteins that cannot be studied by x-ray
      crystallography and NMR. ATR-FTIR requires a little amount of material (1-100
      microg) and spectra are recorded in a matter of minutes. The environment of the
      molecules can be modulated so that their conformation can be studied as a
      function of temperature, pressure, pH, as well as in the presence of specific
      ligands. For instance, replacement of amide hydrogen by deuterium is extremely
      sensitive to environmental changes and the kinetics of exchange can be used to
      detect tertiary conformational changes in the protein structure. Moreover, in
      addition to the conformational parameters that can be deduced from the shape of
      the infrared spectra, the orientation of various parts of the molecule can be
      estimated with polarized IR. This allows more precise analysis of the general
      architecture of the membrane molecules within the biological membranes. The
      present review focuses on ATR-IR as an experimental approach of special interest
      for the study of the structure, orientation, and tertiary structure changes in
      peptides and membrane proteins.

PMID- 11241213
TI  - Liposome-assisted selective polycondensation of alpha-amino acids and peptides.
AB  - The main question of this paper is whether and to what extend lipid bilayers can
      aid in the polycondensation of amino acids and peptides. This means in particular
      how such bilayers can favor the selection of certain sequences out of a large
      number of theoretical possible ones. In a first series of experiments we started
      from a library of Trp-containing dipeptides of the type Trp-X where X is an amino
      acid residue; and we could show that, when adding this mixture to the POPC
      liposomes containing a hydrophobic quinoline condensing agent (EEDQ), only the
      hydrophobic Trp-Trp dipeptide is selected out by the liposomes and transformed
      into a longer oligomer. Trp-oligomers up to 29 monomers long (water insoluble)
      could be obtained by using the matrix support of liposomes. Mixed POPC/DDAB
      liposomes (positive charge) were used to produce co-oligopeptides that contain
      Trp and Glu residues in the same sequence. Arg/Trp and His/Trp containing
      sequences were obtained in presence of negatively charged liposomes (mixed
      POPC/DOPA-liposomes). The polycondensation of racemic NCA-amino acids has been
      studied to clarify if homochiral sequences are produced preferentially in
      presence or absence of liposomes. LC-MS and isotope labeling of the L-amino acid,
      participating in the polymerization reaction achieved this on the level of a
      direct product analysis. So the individual stereoisomer distribution up to a
      polymerization degree of 10 (in the case of Trp) could be determined. The data
      for Trp and other amino acids (Leu, Ile) and amino acid mixtures (Trp/Leu,
      Trp/Ile, Leu/Ile and Trp/Leu/Ile) show that homochiral sequences are produced
      preferentially if compared with a random (Bernoulli) distribution.

PMID- 11241214
TI  - Cation recognition by self-assembled monolayers of oriented helical peptides
      having a crown ether unit.
AB  - Cation recognition of self-assembled monolayers (SAMs) of helical peptides having
      a crown ether unit was investigated by the impedance spectroscopy and cyclic
      voltammetry. Lipo-(Ala-Aib)8-Ala-Cr and Boc-Glu(Cr)-(Ala-Aib)8-Lipoa (Lipo,
      Lipoa, and Cr represent lipoic acid, lipoamide, and amidobenzo-18-crown-6,
      respectively) were synthesized and the helix SAMs were prepared. The peptides
      having a crown ether unit formed SAMs oriented nearly vertically to the
      substrate. The capacitance of the Lipo-(Ala-Aib)(8)-Ala-Cr SAM changed
      specifically with the addition of cations, and the binding constants of the SAM
      were larger than those of the crown ether in aqueous solution because of a large
      dipole moment of the helical peptide. In the case of the Boc-Glu(Cr)-(Ala-Aib)8
      Lipoa SAM, the cation binding to the SAM showed a drastic decrease in the peak
      current of the cyclic voltammetry around 10(-5)M of K+ ion. In either capacitance
      measurement or cyclic voltammetry, the helical peptide SAM played an important
      role in the sensitive response to cations.

PMID- 11241215
TI  - Identification of the ligand-binding site of the BMP type IA receptor for BMP-4.
AB  - Bone morphogenetic proteins (BMPs) belong to the transforming growth factor-beta
      (TGF-beta) superfamily of multifunctional cytokines. BMP induces its signal to
      regulate growth, differentiation, and apoptosis of various cells upon trimeric
      complex formation with two distinct type I and type II receptors on the cell
      surface: both are single-transmembrane serine/threonine kinase receptors. To
      identify the amino acid residues on BMP type I receptor responsible for its
      ligand binding, the structure-activity relationship of the extracellular ligand
      binding domain of the BMP type IA receptor (sBMPR-IA) was investigated by alanine
      scanning mutagenesis. The mutant receptors, as well as sBMPR-IA, were expressed
      as fusion proteins with thioredoxin in Escherichia coli, and purified using
      reverse phase high performance liquid chromatography (RP-HPLC) after digestion
      with enterokinase. Structural analysis of the parent protein and representative
      mutants in solution by CD showed no detectable differences in their folding
      structures. The binding affinity of the mutants to BMP-4 was determined by
      surface plasmon resonance biosensor. All the mutant receptors examined, with the
      exception of Y70A, displayed reduced affinities to BMP-4 with the rank order of
      decreases: I52A (17-fold) approximately F75A (15-fold) >> T64A (4-fold) = T62A (4
      fold) approximately E54A (3-fold). The decreases in binding affinity observed for
      the latter three mutants are mainly due to decreased association rate constants
      while alterations in rate constants both, for association and dissociation,
      result in the drastically reduced affinities for the former two mutants. These
      results allow us to conclude that sBMPR-IA recognizes the ligand using the
      concave face of the molecule. The major ligand-binding site of the BMP type IA
      receptor consists of Phe75 in loop 2 and Ile52, Glu54, Thr62 and Thr64 on the
      three-stranded beta-sheet. These findings should provide a general basis for the
      ligand/type I receptor recognition in the TGF-beta superfamily.

PMID- 11241216
TI  - Engineering of the hydrophobic core of an alpha-helical coiled coil.
AB  - The amino acid sequence that forms the alpha-helical coiled coil structure has a
      representative heptad repeat denoted by defgabc, according to their positions.
      Although the a and d positions are usually occupied by hydrophobic residues,
      hydrophilic residues at these positions sometimes play important roles in natural
      proteins. We have manipulated a few amino acids at the a and d positions of a de
      novo designed trimeric coiled coil to confer new functions to the peptides. The
      IZ peptide, which has four heptad repeats and forms a parallel triple-stranded
      coiled coil, has Ile at all of the a and d positions. We show three examples: (1)
      the substitution of one Ile at either the a or d position with Glu caused the
      peptide to become pH sensitive; (2) the metal ion induced alpha-helical bundles
      were formed by substitutions with two His residues at the d and a positions for a
      medium metal ion, and with one Cys residue at the a position for a soft metal
      ion; and (3) the AAB-type heterotrimeric alpha-helical bundle formation was
      accomplished by a combination of Ala and Trp residues at the a positions of
      different peptide chains. Furthermore, we applied these procedures to prepare an
      ABC-type heterotrimeric alpha-helical bundle and a metal ion-induced
      heterotrimeric alpha-helical bundle.

PMID- 11241217
TI  - Structural bases of collagen stabilization induced by proline hydroxylation.

PMID- 11241218
TI  - Solvent-induced beta-hairpin to helix conformational transition in a designed
      peptide.
AB  - An octapeptide containing a central -Aib-Gly- segment capable of adopting beta
      turn conformations compatible with both hairpin (beta(II') or beta(I')) and
      helical (beta(I)) structures has been designed. The effect of solvent on the
      conformation of the peptide Boc-Leu-Val-Val-Aib-Gly-Leu-Val-Val-OMe (VIII; Boc: t
      butyloxycarbonyl; OMe: methyl ester) has been investigated by NMR and CD
      spectroscopy. Peptide VIII adopts a well-defined beta-hairpin conformation in
      solvents capable of hydrogen bonding like (CD(3))(2)SO and CD(3)OH. In solvents
      that have a lower tendency to interact with backbone peptide groups, like CDCl(3)
      and CD(3)CN, helical conformations predominate. Nuclear Overhauser effects
      between the backbone protons and solvent shielding of NH groups involved in cross
      strand hydrogen bonding, backbone chemical shifts, and vicinal coupling constants
      provide further support for the conformational assignments in different solvents.
      Truncated peptides Boc-Val-Val-Aib-Gly-Leu-Val-Val-OMe (VII), Boc-Val-Val-Aib-Gly
      Leu-Val-OMe (VI), and Boc-Val-Aib-Gly-Leu-OMe (IV) were studied in CDCl(3) and
      (CD(3))(2)SO by 500 MHz (1)H-NMR spectroscopy. Peptides IV and VI show no
      evidence for hairpin conformation in both the solvents. The three truncated
      peptides show a well-defined helical conformation in CDCl(3). In (CD(3))(2)SO,
      peptide VII adopts a beta-hairpin conformation. The results establish that
      peptides may be designed, which are poised to undergo a dramatic conformational
      transition.

PMID- 11241219
TI  - Ligand binding distributions in nucleic acids.
AB  - We illustrate a new method for the determination of the complete binding
      polynomial for nucleic acids based on experimental titration data with respect to
      ligand concentration. From the binding polynomial, one can then calculate the
      distribution function for the number of ligands bound at any ligand
      concentration. The method is based on the use of a finite set of moments of the
      binding distribution function, which are obtained from the titration curve. Using
      the maximum-entropy method, the moments are then used to construct good
      approximations to the binding distribution function. Given the distribution
      functions at different ligand concentrations, one can calculate all of the
      coefficients in the binding polynomial no matter how many binding sites a
      molecule has. Knowledge of the complete binding polynomial in turn yields the
      thermodynamics of binding. This method gives all of the information that can be
      obtained from binding isotherms without the assumption of any specific molecular
      model for the nature of the binding. Examples are given for the binding of Mn(2+)
      and Mg(2+) to t-RNA and for the binding of Mg(2+) and I(6) to poly-C using
      literature data.

PMID- 11241220
TI  - Prediction of the subcellular location of prokaryotic proteins based on a new
      representation of the amino acid composition.
AB  - A new representation of protein sequence is devoted in this paper, in which each
      protein can be represented by a 20-dimensional (20D) vector of unit length.
      Inspired by the principle of superposition of state in quantum mechanics, the
      squares of the 20 components of the vector correspond to the amino acid
      composition. Using the new representation of the primary sequence and Bayes
      Discriminant Algorithm, the subcellular location of prokaryotic proteins was
      predicted. The overall predictive accuracy in the jackknife test can be 3% higher
      than the result of using amino acid composition directly for the database of
      sequence identity is less than 90%, but 5% higher when sequence identity is less
      than 80%. The higher predictive accuracy indicates that the current measure of
      extracting the information from the primary sequence is efficient. Since the
      subcellular location restricting a protein's possible function, the present
      method should also be a useful measure for the systematic analysis of genome
      data. The program used in this paper is available on request.

PMID- 11241221
TI  - Synthesis and conformational features of human salivary mucin C-terminal derived
      peptide epitope carrying Thomsen-Friedenreich antigen: implications for its role
      in self-association.
AB  - The conformational features of a chemically synthesized 23-residue glycopeptide
      construct (II) carrying Gal-beta-(1,3)-alpha-GalNAc and its deglycosylated
      counterpart (I; Gal: galactose; GalNAc: N-acetyl galactosamine) derived from the
      C-terminal domain of human salivary mucin (MUC7) were investigated using CD
      spectroscopy as well as molecular dynamic simulation studies. The corresponding
      deglycosylated peptide (I) was essentially used to compare and study the
      influence of the sugar moiety on peptide backbone conformation. CD measurements
      in aqueous medium revealed that the apopeptide (I) contains significant
      populations of beta-strand conformation while the glycopeptide (II) possess,
      partly, helical structure. This transition in the secondary structure upon
      glycosylation from beta-strand to helical conformation clearly demonstrates that
      the carbohydrate moiety exerts significant influence on the peptide backbone. On
      the other hand, upon titrating structure stabilizing organic cosolvent,
      trifluoroethanol (TFE), both the peptides showed pronounced helical structure.
      However, the propensity for helical structure formation is less pronounced in
      glycopeptide compared to apopeptide suggesting that the bulky carbohydrate moiety
      possibly posing steric hindrance to the formation of TFE-induced secondary
      structure in II. Energy-minimized molecular model for the glycopeptide revealed
      that the preferred helix conformation in aqueous medium appears to be stabilized
      by the hydrogen-bonded salt bridge like interaction between carbohydrate --OH and
      Lys-10 side--N(+)H(3) group. Size exclusion chromatographic analysis of both
      (glyco)peptides I and II showed an apparent Kd of 2.3 and 0.52 microM,
      respectively, indicating that glycopeptide (II) has greater tendency for self
      association. Due to high amphipathic character as well as due to the presence of
      a leucine zipper motif ( approximately LLYMKNLL approximately ), which is known
      to increase the stability at the coiled-coil interface via hydrophobic
      interactions, we propose therefore that, this domain could be one of the key
      elements involved in the self-association of intact MUC7 in vivo. Profound
      conformational effects governed by glycosylation exemplified herein could have
      implications in determining structure-function relationships of mucin
      glycoproteins.

PMID- 11241222
TI  - Structural characterization of lipopeptide agonists for the bradykinin B2
      receptor.
AB  - The conformational features of Pam-Lys(0)-Arg(1)-Pro(2)-Pro(3)-Gly(4)-Phe(5)
      Ser(6)-Pro(7)-Phe(8)-Arg(9)-OH (PKD) and Pam-Gly(-1)-Lys(0)-Arg(1)-Pro(2)-Pro(3)
      Gly(4)-Phe(5)-Ser(6)-Pro(7)-Phe(8)-Arg(9)-OH (PGKD), the Pam-Lys and Pam-Gly-Lys
      analogues of bradykinin, have been determined by high-resolution NMR in a
      zwitterionic lipoid environment. Radical-induced relaxation of the (1)H NMR
      signals was used to probe the topological orientation of the peptides with
      respect to the zwitterionic lipid interface. The radical-induced relaxation and
      molecular dynamics (MD) data indicated that the palmitic acid and N-terminal
      amino acid residues embed into the micelles, while the rest of the polypeptide
      chain is closely associated with the water-micelle interface. Throughout the
      entire nuclear Overhauser effect restrained MD simulation, a nonideal type I beta
      turn was observed in the C-terminus of PKD between residues 6 and 9, and a gamma
      turn was observed in the C-terminus of PGKD between residues 6 and 7. Therefore,
      the additional glycine has a dramatic effect on the structural preferences of the
      biologically important C-terminus, an effect brought about by the interaction
      with the lipid environment. These structural features are correlated to the
      biological activity at the bradykinin B2 receptor.

PMID- 11241223
TI  - Structure of Bombyx mori silk fibroin before spinning in solid state studied with
      wide angle x-ray scattering and (13)C cross-polarization/magic angle spinning
      NMR.
AB  - The structure of a crystalline form of Bombyx mori silk fibroin, commonly found
      before the spinning process (known as silk I), has been proposed as a repeated
      beta-turn type II-like structure by combining data obtained from solid-state two
      dimensional spin-diffusion nuclear magnetic resonance and rotational-echo double
      resonance (T. Asakura et al., J Mol Biol, in press). In this paper, the WAXS
      pattern of alanine-glycine alternating copolypeptide, (Ala-Gly)(15) with silk I
      form which was used for a silk I model of B. mori silk fibroin was observed. The
      pattern calculated with the silk I model proposed by us is well reproduced the
      observed one, indicating the validity of the proposed silk I model. In addition,
      two peptides of the other repeated sequences which contain Tyr or Val residues in
      the silk fibroin,23 were synthesized; (Ala-Gly-Tyr-Gly-Ala-Gly)(5) and (X
      Gly)(15) where X is Tyr for the 7th, 15th and 23th residues, and Val for the 11th
      residue and Ala for other residues. There are no sharp peaks in the WAXS
      patterns, and therefore both samples are in the non-crystalline state. This is in
      agreement with the (13)C CP/MAS NMR result, where the conformation is mainly
      random coil.

PMID- 11241224
TI  - Unraveling double stranded alpha-helical coiled coils: an x-ray diffraction study
      on hard alpha-keratin fibers.
AB  - Transformations of proteins secondary and tertiary structures are generally
      studied in globular proteins in solution. In fibrous proteins, such as hard alpha
      keratin, that contain long and well-defined double stranded alpha-helical coiled
      coil domains, such study can be directly done on the native fibrous tissue. In
      order to assess the structural behavior of the coiled coil domains under an axial
      mechanical stress, wide angle x-ray scattering and small angle x-ray scattering
      experiments have been carried out on stretched horse hair fibers at relative
      humidity around 30%. Our observations of the three major axial spacings as a
      function of the applied macroscopic strain have shown two rates. Up to 4%
      macroscopic strain the coiled coils were slightly distorted but retained their
      overall conformation. Above 4% the proportion of coiled coil domains
      progressively decreased. The main and new result of our study is the observation
      of the transition from alpha-helical coiled coils to disordered chains instead of
      the alpha-helical coiled coil to beta-sheet transition that occurs in wet fibers.

PMID- 11241225
TI  - Why I started the Thyroid Cancer Foundation.
AB  - [Our original introduction to "Listen to the Patient" is published again to
      emphasize the Journal's commitment to this important series.] For more than 50
      years, Cancer has been devoted to exploring every facet of malignant neoplasia,
      from morphology to therapy, from epidemiology to biology, from historical
      perspective to basic science. One aspect, however, needs emphasis, namely, the
      human being who bears the burden of the cancer. For this reason and with the
      encouragement of the Editor, we have undertaken to remedy this situation by
      directing attention to the fears and frustrations, hopes and expectations, and
      feelings and thoughts of all kinds of the person who has cancer, who is worried
      about it, and who is dependent on physicians specialized in its diagnosis and
      management. For doctors to be understanding of the very deep needs of patients
      with cancer, it is requisite that they be privy to authentic, but often unspoken,
      expressions of a patient's anxieties about physical and emotional pain, loss of
      control over personal destiny, and plain dread of dying and of the end of
      cherished relationships. The essay that follows was written by a woman diagnosed
      with cancer who felt herself alone and in need of talking with others who faced
      the same diagnosis. Barrie R. Cassileth, Ph.D. Integrative Medicine Service,
      Memorial Sloan-Kettering Cancer Center, New York, New York A. Bernard Ackerman,
      M.D. Ackerman Academy of Dermatopathology, New York, New York.

PMID- 11241226
TI  - Family information service and hereditary cancer.

PMID- 11241227
TI  - Localized non-Hodgkin lymphoma involving the thyroid gland.
AB  - BACKGROUND: The current study was undertaken to define the natural history and
      patterns of failure of localized non-Hodgkin lymphoma (NHL) involving the thyroid
      gland. METHODS: A retrospective review of 51 patients with Ann Arbor Stage I or
      II NHL involving the thyroid gland was performed. The median age of the patients
      was 59 years. There were 33 females. There were 21 patients with Stage I disease
      and 30 patients with Stage II disease. The International Prognostic Index (IPI)
      was known for 43 patients (it was 0 in 16 patients and > or = 1 in 27 patients).
      Fifteen patients had mediastinal involvement. Four patients underwent
      thyroidectomy, 18 patients received radiation therapy, 5 patients received
      chemotherapy, and 24 patients received combined modality therapy (CMT) with
      chemotherapy and radiation therapy. Treatment modality, patient gender, IPI,
      disease stage, and mediastinal involvement were examined for significance with
      regard to overall survival (OS) and failure free survival (FFS). RESULTS: The 5
      year OS and FFS rates were 64% and 76%, respectively. The 5-year FFS rates by
      treatment regimen were 76% for radiation therapy, 50% for chemotherapy, and 91%
      for CMT (P = 0.15). IPI was found to be the only significant predictor of OS. The
      5-year OS rates were 86% and 50%, respectively, for IPIs of 0 and > or = 1 (P =
      0.02). None of the 5 variables were found to correlate significantly with FFS,
      although the 5-year FFS rates were 93% and 68%, respectively, for IPIs of 0 and >
      or = 1 (P = 0.08). Eleven patients failed treatment. Nine patients had a
      component of distant failure across the diaphragm. CONCLUSIONS: The prognosis of
      patients with localized NHL involving the thyroid gland appears to be very good,
      especially when CMT is used. Distant recurrences appear to account for the
      majority of treatment failures. The IPI was found to be a significant prognostic
      factor for OS and a marginal one for FFS.

PMID- 11241228
TI  - Acquired bleeding disorder in a patient with malignant lymphoma: antibody
      mediated prothrombin deficiency.
AB  - BACKGROUND: Bleeding manifestations secondary to acquired hemostatic
      abnormalities in cancer patients have been well described. Bleeding due to the
      development of hemostatic inhibitors is observed less frequently. In this report,
      the authors describe a patient with a low grade lymphoma who presented with an
      acquired bleeding disorder and abnormal hemostatic screening tests. METHODS:
      Patient plasma samples were collected initially and during the course of
      treatment. Mixing studies and specific coagulation factor assays were performed
      to detect and confirm any deficiencies. Patient immunoglobulin G was isolated
      from plasma, and binding to prothrombin was demonstrated by immunoblot method and
      enzyme-linked immunosorbent assay (ELISA) techniques. RESULTS: Initial
      prolongations in the prothombin time and the activated partial thromboplastin
      time suggested a factor deficiency in the common pathway of coagulation. Factor
      assays confirmed that the coagulation abnormality in this patient was the result
      of an acquired prothrombin (factor II) deficiency. This was confirmed by an
      immunoassay for prothrombin antigen. Further studies demonstrated the presence of
      a noninhibitory antibody to prothrombin that interacted with a calcium dependent
      epitope. CONCLUSIONS: Successful treatment of the lymphoma resulted in clearance
      of the antibody and complete correction of all hemostatic abnormalities and
      manifestations. An acquired prothrombin deficiency has not been reported
      previously in association with a malignancy, and this patient represents the
      first such documented case.

PMID- 11241229
TI  - Natural killer cell lymphoma: report of two pediatric cases, therapeutic options,
      and review of the literature.
AB  - BACKGROUND: Natural killer (NK) cell lymphomas are rapidly fatal malignancies
      that to the authors' knowledge are rare in children. In the current study, the
      authors report the cases of two boys with NK cell lymphomas with refractory
      disease who both were salvaged with high dose chemotherapy and stem cell
      transplantation and compare these patients with those in the published
      experience. METHODS: A comprehensive literature review was performed to identify
      other cases of pediatric patients with NK cell lymphomas, their treatment, and
      outcome. RESULTS: One of the patients in the current study developed two
      recurrences and the other patient experienced early disease progression during
      front-line treatment. Both then were treated with high dose chemotherapy followed
      by stem cell rescue. At last follow-up, the patients remained free of disease at
      15 months and 16 months, respectively, after transplantation (48 months and 22
      months, respectively, from the time of diagnosis). In addition to the 2 patients
      in the current study, the authors found 13 pediatric patients reported in the
      literature to date. Of the 7 patients with localized (Stage I-II) disease, 5
      patients (71%) were reported to be alive 1-107 months after diagnosis. Of the 6
      patients with Stage IV disease, only the 2 patients who received high dose
      chemotherapy and stem cell rescue (33%) were alive at the time of last follow-up
      (at 30 months and 12 months, respectively). Including the patients reported in
      the current study, 9 of 15 children with NK cell lymphoma (all stages) (60%) were
      reported to be alive at the time of last follow-up. CONCLUSIONS: Although
      pediatric NK cell lymphomas rapidly can become fatal, it appears that high dose
      chemotherapy followed by stem cell transplantation is effective therapy,
      especially in patients with advanced or resistant disease. Further follow-up is
      needed to determine whether this treatment approach will be curative.

PMID- 11241230
TI  - Breast carcinomas of limited extent: frequency, radiologic-pathologic
      characteristics, and surgical margin requirements.
AB  - BACKGROUND: Clinical trials established the value of breast-conserving treatment
      (BCT) including the macroscopic removal of the tumor followed by local radiation
      therapy (RT) for Stage I and II invasive carcinomas. The occurrence of local
      tumor recurrence is related to the extent and multifocality of the tumor. Various
      studies aim to identify those tumors that could be proper candidates for
      conventional BCT. Furthermore, recent studies have focused on the identification
      of tumors that may be treated by breast-conserving surgery alone without RT.
      Small, localized tumors theoretically should be the potential candidates for this
      type of treatment. The mammographic and pathologic criteria for the
      identification of tumors with limited extent are not yet established;
      furthermore, the optimal extent of the surgical excision and the method for
      margin examination are controversial. METHODS: Surgical breast-conserving
      procedures were simulated in a review of 135 mastectomy specimens of patients
      treated for an invasive carcinoma (> or = 4 cm in size, all pathologic types
      except invasive lobular carcinoma) who were theoretically eligible for
      conservative treatment. Tumor spread including possible multifocality and
      multicentricity was studied by the technique of correlated specimen radiography
      and pathology. Breast carcinoma of limited extent (BCLE), the proper tumor
      profile for BCT, was defined as having no invasive carcinoma, ductal carcinoma in
      situ, and lymphatic emboli foci beyond 1 cm from the edge of the dominant mass.
      RESULTS: Fifty-three percent of the patients in this series had a BCLE. No
      statistically significant relation was found between BCLE and patient age,
      pathologic size, type and grade of the tumor, lymph node status, mode of
      detection, and mammographic aspect of the index tumor. Based on mammography, the
      absence of calcification or tumor density beyond the edge of index tumor appears
      to be the best predictor for BCLE (P < 0.0001). A 1-cm microscopically tumor free
      margin as the outer rim of a macroscopic surgical margin of 2 cm gives the best
      positive predictive value based on pathology (P < 0.0001). By applying the above
      conditions, 72 of the 135 cancers were identified as being potential BCLE cases
      in this series. However, whereas 64 of these 72 tumors (89%) were correctly
      identified as being true BCLE, 8 (11%) were erroneously identified as such (non
      BCLE cases), having "residual" tumor foci beyond 2 cm from the edge of the
      dominant tumor. CONCLUSIONS: We conclude, that approximately 50% of invasive
      ductal carcinomas may have limited extent. The accuracy of identifying this group
      of cancers, the proper candidates for BCT, by applying state-of-the-art
      mammography and pathology may be as high as 90%. A subset of these tumors might
      represent the potential candidates for treatment with surgery alone without RT.
      As a result, the routine application of BCT complemented by RT would have led to
      the overtreatment of 89% of the patients with a BCLE in this series; conversely,
      11% of the tumors may have recurred without the use of RT. Considering that these
      conclusions are based on a theoretic morphologic model, further clinical studies
      with facilities for high quality team approach in diagnosis and therapy are
      needed to evaluate the impact of BCLE on BCT strategies. The results of this
      study should not justify the withholding of RT outside the context of clinical
      trials.

PMID- 11241231
TI  - Treatment of the jaundiced patient with breast carcinoma: case report and
      alternate therapeutic strategies.
AB  - BACKGROUND: Breast carcinoma in the setting of liver metastases and jaundice
      raises a complex therapeutic dilemma. Not only is the prognosis poor but toxicity
      related to treatment can be unpredictable due to altered drug clearance.
      Guidelines built around dose reduction have been suggested but often do not
      address the varied presentations in clinical medicine. Bilirubin exceeding 5.0
      mg% often is considered an absolute contraindication to the administration of
      chemotherapeutic agents dependent on hepatic metabolism. METHODS: A 55-year-old
      woman with metastatic breast carcinoma to the liver and hyperbilirubinemia was
      treated with sequential, empiric chemotherapy agents with the goal of preventing
      severe toxicity through dose reduction, avoidance of combination therapy, divided
      doses (weekly therapy), and selection of drugs less dependent on hepatic
      clearance. Several attempts did not yield a regimen with a successful response,
      but toxicity was minimal. Eventually, a successful schedule and dose of an agent
      cleared by liver metabolism was individualized for the patient. RESULTS: After
      eight cycles of low dose weekly doxorubicin chemotherapy, the patient's symptoms
      resolved, bilirubin level normalized, and performance status returned to
      baseline. The patient remained on treatment and was alive 12 months later.
      CONCLUSIONS: The authors propose that altering a drug schedule by dividing doses
      may minimize toxicity, maintain dose intensity, and represent an alternative
      strategy for the treatment of patients with hepatic impairment.

PMID- 11241232
TI  - Phase I study of vinorelbine and paclitaxel by 3-hour simultaneous infusion with
      and without granulocyte colony-stimulating factor support in metastatic breast
      carcinoma.
AB  - BACKGROUND: The purpose of the study was to determine the maximum tolerated dose
      (MTD) of vinorelbine and paclitaxel given concomitantly in patients with advanced
      breast carcinoma, the toxicity of this combination, and whether the addition of
      granulocyte colony-stimulating factor (G-CSF) would allow administration of
      higher doses of the combination. METHODS: Between January 1994 and January 1995,
      38 patients were entered on this study. All patients received vinorelbine and
      paclitaxel administered simultaneously over 3 hours and repeated every 21 days as
      frontline therapy for metastatic breast carcinoma. Twenty-five patients (Group 1)
      did not receive prophylactic G-CSF, and 13 patients (Group 2) received
      prophylactic G-CSF. Toxic effects were documented prospectively using the
      National Cancer Institute grading system. RESULTS: One hundred eighty-seven
      (Group 1) and 111 (Group 2) cycles were administered. For Group 1, Grade 3-4
      granulocytopenia was encountered in 72% of the cycles and neutropenic fever in
      30% of the cycles. For Group 2, Grade 3-4 granulocytopenia and neutropenic fever
      were encountered in 23% and 4% of the cycles, respectively. Grade 3-4 fatigue and
      myalgia, respectively, were encountered in 11% and 3% of the cycles in Group 1,
      whereas they were reported in 12% and 1% of the cycles in Group 2. The MTD of
      this combination without prophylactic G-CSF was 25 mg/m2 of vinorelbine and 150
      mg/m2 of paclitaxel, the dose-limiting toxicity (DLT) being neutropenic fever and
      myalgia. The MTD of this combination with G-CSF was 36 mg/m2 of vinorelbine and
      150 mg/m2 of paclitaxel, the DLT being myalgia and fatigue. CONCLUSIONS: The
      authors conclude that vinorelbine and paclitaxel can be safely administered
      concomitantly and are well tolerated. Phase II studies are recommended to test
      the efficacy of this schedule.

PMID- 11241233
TI  - Genetic variation in the tumor necrosis factor-alpha promoter region and in the
      stress protein hsp70-2: susceptibility and prognostic implications in breast
      carcinoma.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) and stress proteins (heat
      shock proteins) are determining factors in the immune response to tumor cells.
      The authors designated a large study to investigate the susceptibility and
      prognostic implications of the genetic variation in TNF-alpha and hsp70-2 in
      breast carcinoma. METHODS: The authors used the polymerase chain reaction and
      restriction enzyme digestion to characterize the variation of the TNF-alpha
      promoter region and that of the hsp70-2 gene in 243 unrelated Tunisian patients
      with breast carcinoma and 174 healthy control subjects. Associations of the
      clinicopathologic parameters and the genetic markers with the rates of the breast
      carcinoma specific overall survival and the disease free survival (DFS) were
      assessed using univariate and multivariate analyses. RESULTS: A highly
      significant association was found between TNF2 homozygous genotype and breast
      carcinoma (relative risk [RR], 4.44; P = 0.006). A high relative risk of breast
      carcinoma was found to be associated with one hsp70-2 homozygous genotype (P2/P2;
      RR, 7.12; P = 0.0001). The TNF2 homozygous genotype showed a significant
      association with reduced DFS and/or overall survival by univariate test.
      Conversely, P2-hsp70-2 homozygous genotype associated with increased overall
      survival but not with DFS. Multivariate analysis retained significance for TNF2
      homozygous genotype as an independent prognostic indicator for both DFS (RR,
      2.75; P = 0.01) and overall survival (RR, 4.08; P = 0.01). CONCLUSIONS: Genetic
      variation in TNF-alpha and hsp70-2 may represent not only markers for the
      increased risk of breast carcinoma but also may predict the clinical outcome.

PMID- 11241234
TI  - The role of psychosocial factors in the development of breast carcinoma: Part I.
      The cancer prone personality.
AB  - BACKGROUND: The authors conducted the current study to determine whether
      personality predisposes some individuals to develop cancer. METHODS: The current
      study examined the role of personality variables in 2224 older women recalled for
      assessment after routine mammography in a breast screening program. Using a
      semiprospective design, subjects completed self-report measures of defense style,
      locus of control, emotional expression and control, self-esteem, trait anxiety,
      and state anxiety and depression while waiting for medical examination.
      Multivariate analysis of variance was used to control for known risk factor
      variables and to examine differences between 3 control groups (normal tissue
      controls, benign/cystic controls not requiring biopsy, and benign biopsy
      controls) and 298 breast carcinoma subjects. RESULTS: No differences were
      detected between breast carcinoma subjects and controls based on measures of
      mature, immature, and neurotic defense style; locus of control of behavior;
      emotional expression-in, emotional expression-out, and emotional control; self
      esteem; anxiety; or depression. CONCLUSIONS: The results of the current study
      found no evidence to support an independent association between these personality
      measures and the development of breast carcinoma. [See accompanying article on
      pages 686-97, this issue.]

PMID- 11241235
TI  - The role of psychosocial factors in the development of breast carcinoma: Part II.
      Life event stressors, social support, defense style, and emotional control and
      their interactions.
AB  - BACKGROUND: The evidence supporting an association between life event stress and
      breast carcinoma development is inconsistent. METHODS: Five hundred fourteen
      women requiring biopsy after routine mammographic breast screening were
      interviewed using the Brown and Harris Life Event and Difficulties Schedule.
      Other psychosocial variables assessed included social support, emotional control,
      and defense style. Biopsy results identified 239 women with breast carcinoma and
      275 women with benign breast disease. Multiple logistic regression analysis was
      used to distinguish between breast carcinoma subjects and benign breast disease
      controls based on these psychosocial variables and their interactions. RESULTS:
      The findings of the current study revealed a significant interaction between
      highly threatening life stressors and social support. Women experiencing a
      stressor objectively rated as highly threatening and who were without intimate
      emotional social support had a ninefold increase in risk of developing breast
      carcinoma. CONCLUSIONS: Although there was no evidence of an independent
      association between life event stress and breast carcinoma, the findings of the
      current study provided strong evidence that social support interacts with highly
      threatening life stressors to increase the risk of breast carcinoma
      significantly. [See also accompanying article on pages 679-85, this issue.]

PMID- 11241236
TI  - Clinicopathologic study of early-stage mucinous gastric carcinoma.
AB  - BACKGROUND: Mucinous gastric carcinoma (MGC) is rare, and whether MGC behaves
      more aggressively than nonmucinous gastric carcinoma (NGC) is controversial. To
      the authors' knowledge, there is no study of early-stage MGC, and the pathology
      and prognosis of patients who have early MGC is unknown. The aim of this study
      was to clarify the clinicopathologic characteristics of early MGC. METHODS:
      Pathologic and prognostic data of 30 patients who had early MGC were compared
      retrospectively against data of 165 patients who had early NGC and 58 patients
      who had advanced MGC. We defined MGC as a tumor in which more than half of the
      tumor area contained extracellular mucin pools. We defined early gastric
      carcinoma as a tumor restricted to the mucosa or to the mucosa and submucosa (T1,
      International Union Against Cancer [UICC], 1997) regardless of lymph node
      metastasis. RESULTS: Early MGC tumors, compared with early NGC tumors, were
      characterized by macroscopic elevation (57% vs. 23%, P < 0.01) and invasion to
      the submucosa (83% vs. 44%, P < 0.01). Tumor size, frequency of lymph node
      metastasis, and patient outcome did not differ between the two types, and no
      patient with early MGC died of recurrence during a median follow-up period of 67
      months. When early MGC was compared with advanced MGC, tumor size (2.9 cm vs. 9.4
      cm, P < 0.01), frequency of lymph node metastasis (10% vs. 88%,P < 0.01), total
      gastrectomy (0% vs. 52%, P < 0.01), noncurative surgery (0% vs. 38%, P < 0.01),
      and recurrent death (0% vs. 57%, P < 0.01) differed significantly. CONCLUSIONS:
      Our results indicated that although the macroscopic features of early MGC
      differed from those of early NGC, patient prognosis and the frequency of lymph
      node metastasis did not differ. Neither did mucinous histology seem to influence
      outcome adversely after gastrectomy.

PMID- 11241237
TI  - Phase II study of irinotecan as first-line chemotherapy for patients with
      advanced colorectal carcinoma.
AB  - BACKGROUND: The objective of this multicenter, open-labeled, Phase II study
      performed in Spain was to assess the efficacy and safety of irinotecan (CPT-11)
      as first-line chemotherapy for patients suffering from advanced colorectal
      carcinoma (CRC). METHODS: Patients with histologically proven CRC and at least
      one bidimensionally measurable lesion, ages 18-70 years, with a performance
      status < or = 2, normal analytical values, and no prior chemotherapy or only
      adjuvant chemotherapy completed before study entry were selected. The treatment
      schedule was CPT-11 350 mg/m(2) intravenously administered once every 3 weeks.
      Both tumor response and toxicity were assessed using the World Health
      Organization and National Cancer Institute common toxicity criteria. Changes in
      performance status, weight, and symptoms also were measured. RESULTS: Sixty-five
      patients (44 chemotherapy-naive patients and 21 patients who completed prior
      adjuvant treatment) were enrolled. Of these, 24.7% of patients responded to the
      treatment, and 41.5% of patients had stable disease. Patients who had not
      received prior adjuvant chemotherapy had a lower rate of progression on therapy
      (27.3%) compared with those who had received prior adjuvant chemotherapy (42.9%).
      The median survival was 19.9 months (range, 0.3-29.3 months). No significant
      differences were found in the median survival between chemotherapy-naive patients
      and patients who had received previous chemotherapy. Grade 3-4 diarrhea and
      neutropenia were the most frequent severe toxic events, which were observed in
      23.1% and 30.8% of patients and in 5.9% and 10.9% of the cycles, respectively.
      CONCLUSIONS: The current antitumor efficacy results show that 350 mg/m(2) of CPT
      11 administered every 3 weeks is an active and feasible first-line chemotherapy
      regimen for patients with CRC. Finally, the overall safety data confirmed that
      CPT-11 is a well tolerated treatment.

PMID- 11241238
TI  - Irinotecan and chronomodulated infusion of 5-fluorouracil and folinic acid in the
      treatment of patients with advanced colorectal carcinoma: a phase I study.
AB  - BACKGROUND: Irinotecan (CPT-11) is an active drug in the treatment of patients
      with advanced colorectal carcinoma. The infusion of 5-fluorouracil (5-FU)
      according to circadian rhythms was used previously to decrease toxicity and to
      increase its therapeutic efficacy. The objective of this study was to establish
      the maximum tolerated dose (MTD) of CPT-11 together with a chronomodulated
      infusion of 5-FU and the l-form of folinic acid (FA). Secondary end points were
      the assessment of activity and quality of life (QoL). METHODS: Twenty-six
      patients with advanced colorectal carcinoma who had received previous treatment
      with 5-FU were entered on this Phase I study. At least three patients were
      recruited at each dose level. The CPT-11 starting dose was 175 mg/m(2) on Day 1
      with an increase of 50 mg/m2 per dose level. A daily administration of
      chronomodulated 5-FU (900 mg/m2; peak delivery rate at 04:00) and FA (175 mg/m2;
      peak delivery rate at 04:00) for 5 days every 3 weeks was given with CPT-11.
      After the first three patients, the 5-FU dose was reduced to 700 mg/m2 per day
      due to toxicity. No intrapatient dose escalation was allowed. RESULTS: One
      hundred sixty-one courses were delivered. Dose-limiting toxicity was observed
      during the first course in seven patients (27%). Four patients developed
      neutropenia, with one patient reporting febrile neutropenia, two patients
      reporting severe stomatitis, and six patients reporting severe diarrhea. CPT-11
      MTD was reached at 350 mg/m2 when a toxic death was observed with a recommended
      dose of 325 mg/m2. Six partial responses were observed (23%). The median duration
      of response and the progression free and overall survival rates were 199 days,
      175 days, and 359 days, respectively. QoL was not affected by the treatment.
      CONCLUSIONS: The recommended dose for Phase II trials is 325 mg/m2 CPT-11 on Day
      1, which is similar to the dose given as a single agent, together with a 5-day
      chronomodulated infusion of 700 mg/m2 5-FU and 175 mg/m2 FA. Intensification of
      this schedule every 2 weeks should be achievable.

PMID- 11241239
TI  - Genetic changes in colorectal carcinoma tumors with liver metastases analyzed by
      comparative genomic hybridization and DNA ploidy.
AB  - BACKGROUND: Liver metastases are found in 10% of primary colorectal malignancies,
      and they affects the prognosis of patients with colorectal carcinoma. The authors
      investigated DNA copy number aberrations by using comparative genomic
      hybridization (CGH) and DNA ploidy alterations by using flow cytometry (FCM) in
      patients with primary colorectal carcinoma (primary tumors). To determine whether
      there are characteristic DNA copy number alterations that contribute to liver
      metastasis, cytogenetic aberrations were examined by CGH and FCM. METHODS: The
      authors analyzed 35 primary tumors, including 16 primary tumors with liver
      metastasis, by using CGH and FCM. RESULTS: Increases in DNA copy numbers were
      detected in 6q (5 of 16 tumors), 7q (6 of 16 tumors), 8q (7 of 16 tumors), 9p (5
      of 16 tumors), 13q (8 of 16 tumors), 20p (9 of 16 tumors), and 20q (15 of 16
      tumors) in primary tumors with liver metastases. Decreases in DNA copy numbers
      were found in 17p (5 of 16 tumors), 18p (6 of 19 tumors), 18q (8 of 16 tumors),
      and 22q (5 of 16 tumors). In contrast, primary tumors without liver metastasis
      showed gains in chromosome arms 8q (2 of 19 tumors), 13q (2 of 19 tumors), 20p (6
      of 19 tumors), and 20q (5 of 19 tumors); however, they showed no gains in 6q or
      7q and showed losses in chromosome arms 17p (2 of 19 tumors), 18p (4 of 19
      tumors), 18q (6 of 19 tumors), and 22q (5 of 19 tumors). There was a significant
      difference in the frequency of DNA copy number gains and losses in 6q (P < 0.05),
      7q (P < 0.01), 8q (P < 0.05), 13q (P < 0.05), and 20q (P < 0.01), respectively,
      between primary tumors with and without liver metastases. The differences in the
      DNA index were not significant between the two groups of primary tumors.
      CONCLUSIONS: In liver metastases of primary tumors from patients with colorectal
      carcinoma, a correlation between DNA copy number aberrations and gains of
      chromosome arms 6q, 7q, 8q, 13q, and 20q is suggested.

PMID- 11241240
TI  - P53 mutations in primary tumors and subsequent liver metastases are related to
      survival in patients with colorectal carcinoma who undergo liver resection.
AB  - BACKGROUND: The appearance of p53 mutations in colorectal carcinoma was
      determined, independent of differentiation and tumor stage of the primary tumors,
      in relation to the survival of patients who were scheduled to undergo liver
      resection. METHODS: Tumor material was analyzed for p53 mutations in primary
      colorectal tumors and subsequent liver metastases from 41 consecutive patients
      who were scheduled to undergo surgical liver resection. DNA sequencing and
      immunohistochemical staining of p53 protein within tumor nuclei were performed.
      RESULTS: Primary tumors displayed p53 mutations within exons 5-9 in 41% of
      patients. No mutations were found in exons 4, 10, or 11. Forty-one percent of
      metastatic lesions had the same single mutation that was found in the primary
      tumor, whereas 11% of metastatic lesions had one additional mutation within exons
      5-9; 22% had mutations only in their liver metastases, whereas corresponding
      primary tumors displayed wild-type p53. None of the patients had mutated p53 in
      their primary tumor and wild type in their metastases. Survival after undergoing
      liver resection was correlated negatively (P < 0.05-0.01) with Duke Stages A-D
      classification of the primary tumors, tumor differentiation, and radicality (>
      0.7-0.8 mm) of resected liver metastases. CONCLUSIONS: The presence of p53
      mutations in patients with metastatic lesions was related significantly (P <
      0.003) to better survival after the patients underwent liver resection compared
      with patients with wild type p53 in their metastatic lesions. This finding was
      not related to covariates, such as Duke classification, tumor differentiation,
      type of liver metastasis, or metastatic radicality during resections.
      Explanations for this unexpected finding remain unclear, although the authors
      speculate that occult tumor cells with p53 mutations may be less responsive to
      growth factor(s) exposure during hepatic regeneration after resection.

PMID- 11241241
TI  - Lipoxygenase-5 is overexpressed in prostate adenocarcinoma.
AB  - BACKGROUND: Epidemiologic studies suggest that populations that consume large
      amounts of dietary fat are at greater risk for prostate carcinoma. Arachidonic
      acid and its precursor, linoleic acid, are major ingredients of animal fats and
      many vegetable oils that are used in the regions where prostate carcinoma is
      prevalent. The metabolism of arachidonic acid by either the cyclooxygenase
      pathway or the lipoxygenase pathway generates eicosanoids, which have been
      implicated in the pathogenesis of a variety of human diseases, including cancer,
      and are now believed to play important roles in tumor promotion, progression, and
      metastasis. Studying these pathways in specimens from patients with prostate
      carcinoma, the authors recently demonstrated the overexpression of cyclooxygenase
      2 in prostate adenocarcinoma. In the current study, the authors report the
      overexpression of lipoxygenase-5 (5-LO) in samples from patients with prostate
      adenocarcinoma. METHODS: Employing 22 pair-matched benign and malignant tissue
      samples that were obtained from the same patients with prostate carcinoma, the
      expression of 5-LO was determined using reverse transcriptase-polymerase chain
      reaction, immunoblotting, and immunohistochemistry and by measuring the levels of
      5-hydroxyeicosatetraenoic acid (5-HETE) by radioimmunoassay. RESULTS: The mean
      level of 5-LO mRNA was six-fold greater (P < 0.001) in malignant tissue compared
      with benign tissue. The immunoblot analysis demonstrated that, compared with
      benign tissue, 5-LO protein was overexpressed in 16 of 22 samples examined and
      was 2.6 fold greater (P < 0.001) in malignant tissue. Immunohistochemical studies
      further verified 5-LO up-regulation in malignant tissue that was not present in
      benign tissue. The levels of 5-HETE, which is a metabolic product of arachidonic
      acid, was found to be 2.2-fold greater (P < 0.001) in malignant tumor tissue
      compared with benign tissue. CONCLUSIONS: To the authors' knowledge, this is the
      first in vivo study showing overexpression of 5-LO in patients with prostate
      carcinoma. This study suggests that inhibitors of arachidonic acid pathway in
      general and selective 5-LO inhibitors in particular may be useful for prevention
      or therapy in patients with prostate carcinoma.

PMID- 11241242
TI  - Long term follow-up of mass screening for prostate carcinoma in men with initial
      prostate specific antigen levels of 4.0 ng/ml or less.
AB  - BACKGROUND: Long term follow-up for subjects whose initial prostate specific
      antigen (PSA) levels were 4.0 ng/mL or lower was conducted to investigate the
      proper interval for PSA screening. METHODS: Eight thousand five hundred ninety
      five men aged 50 years or older with an initial PSA level of 4.0 ng/mL or lower
      were screened with tumor marker measurement and/or digital rectal examination
      (DRE) and/or transrectal ultrasonography as a first step in the mass screening,
      and a prostate biopsy was performed for individuals with abnormal findings.
      RESULTS: Cancer was detected in 0.18% (8 of 4526), 1.0% (27 of 2724), and 3.6%
      (49 of 1345) of men whose initial PSA levels were lower than 1.0, 1.0-1.9, and
      2.0-4.0 ng/mL, respectively. Among these prostate carcinoma cases, 25% (6 of 8),
      56% (15 of 27), and 63% (31 of 49) were detected by abnormal PSA in patients with
      initial PSA levels lower than 1.0, 1.0-1.9, and 2.0-4.0 ng/mL, respectively. The
      detection rates of prostate carcinoma within 3 years after the initial visit were
      0.07%, 0.24%, and 1.2% in cases with initial PSA levels lower than 1.0, 1.0-1.9,
      and 2.0-4.0 ng/mL, respectively. CONCLUSIONS: It is recommended that DRE and PSA
      measurements should be performed once every 3 years in individuals with initial
      PSA levels of less than 1.0 ng/mL. The prostate carcinoma detection rate
      increased over time in individuals with initial PSA levels of 1.0 to 4.0 ng/mL,
      especially in cases with 2.0-4.0 ng/mL, and annual measurement of PSA was more
      useful than DRE. Therefore, it is recommended that PSA screening should be
      performed once every year for individuals with initial PSA levels of 1.0 to 4.0
      ng/mL.

PMID- 11241243
TI  - Early stage uterine papillary serous carcinoma of the endometrium: effect of
      adjuvant whole abdominal radiotherapy and pathologic parameters on outcome.
AB  - BACKGROUND: Uterine papillary serous carcinoma (UPSC) is an aggressive subtype of
      endometrial cancer, behaving like ovarian epithelial cancers and having a
      predilection for transperitoneal relapse. Within this subtype of uterine cancers,
      predictors of outcome and the role of adjuvant therapies have not been firmly
      established, to the authors' knowledge. METHODS: Between 1985-1995, 78 patients
      who had International Federation of Gynecology and Obstetrics (FIGO) Stage I, II,
      or IIIa UPSC (based on positive washings only) were seen at the British Columbia
      Cancer Agency. During this time, the authors had a policy of offering adjuvant
      pelvic, paraaortic and whole-abdominal radiotherapy (WART) to these patients.
      Fifty-eight patients received adjuvant WART, and 20 received lesser or no
      adjuvant therapy. The authors undertook a retrospective analysis of pathology
      with quantification of the percentage of papillary serous component (% PSC) and
      p53 expression. Pathology was retrieved and reviewed on 62 patients; p53 staining
      was performed on blocks from the hysterectomy specimen in 46 cases. Pathologic
      parameters, stage, and adjuvant therapy were correlated with clinical outcome in
      a multivariate analysis. RESULTS: Median follow-up was 52 months (3-139 mos) and
      the 5-year disease-specific survival rate was 66.2%. The 58 patients who received
      adjuvant WART had a significantly better 5-year disease-specific survival than
      those 20 patients who did not, 74.9% versus 41.3% (P = 0.04). Multivariate
      analysis showed that % PSC and p53 were not significant predictors of outcome for
      early stage UPSC. Of the factors examined, only FIGO stage and WART significantly
      predicted improved outcome (P = 0.02 and 0.04, respectively). CONCLUSIONS: The
      current study demonstrated a significant difference in the outcomes of patients
      who had FIGO Stage I compared with Stage II UPSC. In the current series of
      patients, the authors were not able to predict outcome based on % PSC or p53
      expression. The current study results with WART were promising, and WART merits
      further study.

PMID- 11241244
TI  - Primary invasive carcinoma of the vagina: treatment with interstitial
      brachytherapy.
AB  - BACKGROUND: Because primary carcinoma of the vagina comprises less than 2% of all
      gynecologic malignancies, the reported experience in the treatment of large
      numbers of patients is available only from a few major centers and most often
      encompasses a variety of differences in treatment selection and technique. The
      objective of this study was to assess the long term results of an interstitial
      iridium-192 afterloading implant technique using the Syed-Neblett dedicated
      vaginal plastic template. METHODS: Patients who were treated from 1976 to 1997
      were examined retrospectively. RESULTS: Seventy-one patients underwent
      interstitial implantation with (n = 61 patients) or without external beam
      radiotherapy. The median age was 59 years (range, 16-86 years). Patients were
      staged according to the International Federation of Gynecology and Obstetrics
      system and included Stage I (n = 10 patients), Perez modification Stage IIA (n =
      14 patients), Perez modification Stage IIB (n = 25 patients), Stage III (n = 15
      patients), and Stage IV (n = 7 patients). Each implant delivered an approximately
      20-gray (Gy) minimum tumor dose, with the total tumor dose reaching 80 Gy with
      integrated external beam radiotherapy. Local control was achieved in 53 patients
      (75%). The median follow-up was 66 months (range, 15-163 months), and the 2-year,
      5-year, and 10-year actuarial disease free survival rates are 73%, 58%, and 58%,
      respectively. By stage, 5-year disease free survival rates included Stage I, 100%
      of patients; Stage IIA, 60% of patients; Stage IIB, 61% of patients; Stage III,
      30% of patients; and Stage IV, 0% of patients. The factors disease stage and
      primary lesion size independently influenced the survival rates. Significant
      complications occurred in 9 patients (13%) and included necrosis (n = 4
      patients), fistulae (n = 4 patients), and small bowel obstruction (n = 1
      patient). CONCLUSIONS: Interstitial irradiation can effect local control in the
      majority of patients with primary carcinoma of the vagina with acceptable
      morbidity. Long term cure is demonstrable in patients with Stage I-III disease.

PMID- 11241245
TI  - Perioperative blood transfusion in hepatocellular carcinomas: influence of
      immunologic profile and recurrence free survival.
AB  - BACKGROUND: The postoperative recurrence of hepatocellular carcinomas (HCC)
      associated with perioperative blood transfusion has been the subject of
      controversy. The authors prospectively investigated the relation between
      perioperative allogeneic blood transfusions, the recurrence free survival, and
      the immunologic profiles of patients with HCC who had undergone curative hepatic
      resections. METHODS: One hundred eight patients were divided into two groups: a
      transfused group (n = 53) and a nontransfused group (n = 55), according to their
      perioperative transfusion history. The subsets of lymphoid cells, natural killer
      cell activity and the phytohemagglutinin (PHA) response were all measured
      preoperatively, and at 1, 2, and 4 weeks and at 3 and 6 months after the
      hepatectomy. The recurrence free survival rate then was compared between these
      two groups. RESULTS: There were no significant differences between these two
      groups with respect to histologic findings, clinical stage, type of resection,
      pathologic data, and the recurrence free survival rate. Postoperative levels of
      the CD8 in the transfused group were elevated as compared with the nontransfused
      group, and the PHA response of the transfused patients was significantly
      increased at 7 postoperative days. Natural killer cell activity of the transfused
      patients was decreased at 7 postoperative days, as compared with the
      nontransfused patients, but there was no significant difference. CONCLUSIONS:
      Although allogeneic blood transfusion may have immunosuppressive effects,
      perioperative blood transfusions did not influence the cancer free survival rate
      in patients with hepatocellular carcinoma.

PMID- 11241246
TI  - Primary pulmonary osteosarcoma: case report and molecular analysis.
AB  - BACKGROUND: Primary pulmonary osteosarcoma is an extremely rare malignancy. To
      date, only 12 cases have been reported, with a high mortality rate. The authors
      report on a newly diagnosed patient and describe investigations that were
      performed using immunohistochemistry and comparative genomic hybridization (CGH).
      METHODS: The clinical course of a woman age 37 years is presented. Along with
      routine histologic examination, immunohistochemistry was used to demonstrate
      differentiation-associated proteins, oncoproteins, and other markers; CGH
      analysis for genomic alterations; and histochemistry to demonstrate alkaline
      phosphatase activity. RESULTS: Immunohistochemical analysis showed varying
      expression patterns using antibodies against a panel of tumor markers. Most
      notable was high overexpression of BCL-2 and cyclin D. CGH analysis showed that
      this neoplasm contained a much higher level of genetic aberrations compared with
      skeletal osteosarcoma. CONCLUSIONS: This tumor exhibited features common to
      skeletal osteosarcomas but also had some unique features. Genome analysis
      suggests that this tumor has several genetic aberrations in common with
      extraskeletal osteosarcoma. The novel regions of instability identified within
      the tumor genome may contribute toward the unique tumor phenotype and relative
      chemoresistance.

PMID- 11241247
TI  - Neuroblastomas of infancy exhibit a characteristic ganglioside pattern.
AB  - BACKGROUND: Gangliosides are membrane-bound glycolipid molecules particularly
      prominent in neural tissue. Changes in ganglioside expression during embryologic
      development result from a shift in biosynthesis from the fetal b pathway to the
      adult a pathway. Tumor gangliosides may play a role in the clinical behavior of
      certain subtypes of neuroblastoma. Because neuroblastoma, which presents in
      infancy, has a different biologic and clinical phenotype than that which presents
      in older children, the authors determined whether differences in ganglioside
      biosynthesis exist between these two neuroblastoma subgroups. METHODS: Sixty
      eight tumor specimens (25 diagnosed by screening and 43 diagnosed clinically)
      were obtained from the Quebec Neuroblastoma Screening Project. Gangliosides were
      isolated and purified by solvent partitioning, separated by high performance thin
      layer chromatography, and quantitated by scanning densitometry. The sum of a and
      b pathway gangliosides were determined for each tumor. RESULTS: Gangliosides of
      the b (fetal) pathway predominated in both screened and clinically diagnosed
      tumors of patients younger than 1 year of age. Twenty-three of 25 screened
      patients (92%) and 21 of 23 patients with clinically diagnosed tumors at younger
      than 1 year of age (91%) had tumor b pathway ganglioside content greater than
      60%. In contrast, tumors of only 8 of 20 patients 1 year or older (40%) had b
      pathway ganglioside predominance. Predominance of b pathway tumor gangliosides
      correlated with improved outcome. Event free survival was significantly higher
      among patients with b pathway ganglioside tumor content greater than 60% versus
      those with b pathway ganglioside tumor content less than 60% (118.1 +/- 3.9
      months vs. 69.2 +/- 8.6 months, P < 0.01). CONCLUSIONS: Fetal patterns of
      ganglioside biosynthesis predominate in neuroblastoma tumors from patients
      younger than 1 year of age and adult patterns of ganglioside biosynthesis
      predominate in tumors from older children, supporting the view that neuroblastoma
      consists of distinct but overlapping disorders, and that gangliosides may play a
      biologic role in the clinical differences among these patients.

PMID- 11241248
TI  - Clinicopathologic analysis of patients with adult rhabdomyosarcoma.
AB  - BACKGROUND: Rhabdomyosarcoma (RMS) in adults (age > or = 16 years) is rare,
      accounting for less than 3% of adult soft tissue sarcomas. There is little
      information describing the disease biology or clinicopathologic factors that
      influence survival in adults with RMS. The objective of this study was to define
      the factors in patients with adult RMS that predict outcome, disease progression,
      and survival. METHODS: Eighty-four adult patients with a pathologic diagnosis of
      RMS that was confirmed by immunohistochemistry were identified by a prospective
      inpatient data base during the period 1982--1999 and were analyzed for disease
      specific survival and metastasis free survival using the Kaplan-Meier actuarial
      method. Statistical significance was evaluated using the log-rank test for
      univariate influence and a Cox regression model for multivariate influence.
      RESULTS: The median disease specific survival was 22 months. Patient age, extent
      of disease, tumor size at the time of diagnosis, and margin status after
      resection were significant predictors of disease specific survival. Patients who
      underwent a complete resection had a significantly longer median survival (105
      months) compared with any other subgroup of patients. The histologic subtype did
      not predict patient survival but did vary with patient age. Most notably, the
      proportion of the pleomorphic subtype increased with advancing age, accounting
      for 42% of RMS in patients over the age of 40 years. CONCLUSIONS: The most
      important predictors of outcome in patients with adult RMS are patient age, tumor
      size, extent of disease, and margin status after resection. In contrast to
      patients with pediatric RMS, no association was noted between survival and
      histologic subtype in this group of patients with adult RMS. All histologic
      subtypes of RMS are aggressive malignancies with poor disease specific survival
      despite aggressive multimodality management.

PMID- 11241249
TI  - For Valentine's Day: epithelial sheath neuroma.

PMID- 11241250
TI  - Central venous device-related infection and thrombosis in patients treated with
      moderate dose continuous-infusion interleukin-2.
AB  - BACKGROUND: This study was performed to determine the incidence of central venous
      device-related blood stream infection and thrombosis in patients treated with
      moderate dose continuous-infusion interleukin-2 (IL-2). METHODS: The records of
      160 consecutive patients treated at the University of Wisconsin Hospital and
      Clinics, between June 1990 and June 1997, with moderate dose continuous-infusion
      IL-2 (IL-2 [1.5-3.0 x 10(6) U/m(2)/day] Hoffman-LaRoche, Nutley, NJ or IL-2 [4.5
      x 10(6) U/m(2)/day] Chiron Corporation, Berkley, CA) were reviewed
      retrospectively. The majority of patients had metastatic melanoma (78 patients)
      or renal cell carcinoma (70 patients). All of the patients had a surgically
      implanted central venous device placed before starting IL-2 therapy; 89% of these
      were cuffed Hickman catheters. Eighty-four patients received 1 mg of warfarin per
      day as prophylaxis against device-related thrombosis; none received periinsertion
      prophylactic antibiotics. RESULTS: Twenty-one patients (13%) developed central
      venous device-related bloodstream infection (DRBSI) during the study period, a
      rate of 2 DRBSI per 1000 device-days. DRBSIs were associated with the type of
      immunotherapy given with IL-2 (P = 0.01) and with thrombosis (odds ratio, 4.1;
      95% confidence interval, 1.5-11.4; P = 0.008) but not with patient gender, type
      of cancer, duration of the central device, or site of device placement. Twenty
      six patients (16%) developed central venous device-related thrombosis (DRT)
      during immunotherapy. Low dose warfarin did not appear to prevent thrombosis.
      Device-related thrombosis was associated with DRBSI but not with patient gender,
      type of cancer, type of device, duration or location of device, or concomitant
      immunotherapy. CONCLUSIONS: Central venous DRBSI and DRT are significant
      complications that can occur during moderate dose continuous-infusion IL-2
      therapy. The risk of DRBSI appears lower than the risk reported with high dose IL
      2 therapy by previous investigators. The risk of DRT appears to be higher than
      the risk reported for patients with similar devices but not given IL-2. Low dose
      warfarin did not prevent DRT when started after device placement.

PMID- 11241251
TI  - Phase I bioequivalency study of MitoExtra and mitomycin C in patients with solid
      tumors.
AB  - BACKGROUND: This study compares serum pharmacokinetics, urinary excretion
      patterns, and relative bioequivalencies of single doses of MitoExtra (ME;
      SuperGen, San Ramon, CA) and mitomycin C (MMC). METHODS: Thirty-five patients
      were entered into this open-label, single-institution, crossover study with 2
      treatment arms. Each patient received alternating courses of ME and MMC as 15
      mg/m(2) single intravenous doses via a short intravenous infusion. Patients were
      sequentially assigned to receive either ME or MMC as their first treatment
      course. The courses were given in 6-week intervals and could be repeated up to 4
      times in patients with responding disease. Pharmacokinetic parameters were
      analyzed during the first two courses of therapy. RESULTS: The noncompartmental
      pharmacokinetic analysis conducted on serum and urine data obtained from patients
      who received both ME and MMC indicates that the kinetic disposition of these two
      formulations is similar. This is evident when the mean (+/- standard deviation)
      values of the various pharmacokinetic parameters are compared. There were no
      significant differences in any of the kinetic parameters obtained between
      treatments in all patients examined. The statistical evaluation conducted on the
      25 patients that completed both arms of the 2-way pharmacokinetic crossover
      demonstrates that ME is bioequivalent to MMC. Hematologic and nonhematologic
      toxicities were similar between the two treatments. There were three clinically
      significant infusion-related complications associated with MMC administration and
      none associated with ME. CONCLUSIONS: The similar pharmacokinetics of MMC and ME
      suggest complete release of MMC from the hydroxypropyl-Beta-cyclodextrin carrier
      contained in the ME formulation. Further studies are needed to define the
      pharmacodynamics, toxicity, and efficacy of this drug-carrier complex.

PMID- 11241252
TI  - Tumor gelatinases and invasion inhibited by the green tea flavanol
      epigallocatechin-3-gallate.
AB  - BACKGROUND: Given the association of consumption of green tea with prevention of
      cancer development, metastasis, and angiogenesis, the effect of the main flavanol
      present, epigallocatechin-3-gallate (EGCG), on two gelatinases most frequently
      overexpressed in cancer and angiogenesis (MMP-2 and MMP-9) and on tumor cell
      invasion and chemotaxis were examined. METHODS: Zymography, Western blotting, and
      enzyme linked immuoadsorbent assay were used to analyze the effect of EGCG on MMP
      2 and MMP-9 activity, whereas its effect on tumor cell invasion and chemotaxis
      was examined using modified Boyden chamber assays. RESULTS: A Zn2+ chelation
      independent, dose-dependent, noncompetitive inhibition by EGCG of both
      gelatinases was found at concentrations 500 times lower than that reported to
      inhibit urokinase. Tumor cell invasion of a reconstituted basement membrane
      matrix, but not chemotaxis, was reduced by 50% with EGCG concentrations
      equivalent to that in the plasma of moderate green tea drinkers, and 2 orders of
      magnitude below those of tissue inhibitors of MMPs. Although higher
      concentrations of EGCG were associated with increased levels of both cell
      associated gelatinases and their activator MT1-MMP, no increased gelatinase
      activation was found, and TIMP-1 and TIMP-2 inhibitors were up-regulated.
      Finally, concentrations of EGCG active in restraining proliferation and inducing
      apoptosis of transformed cells were more than 100 times lower than those reported
      for normal cells. CONCLUSIONS: Epigallocatechin-3-gallate is a potent inhibitor
      of gelatinases and an orally available pharmacologic agent that may confer the
      antiangiogenic and antimetastatic activity associated with green tea.

PMID- 11241253
TI  - Calcium supplements interact significantly with long-term diet while suppressing
      rectal epithelial proliferation of adenoma patients.
AB  - BACKGROUND: Calcium supplements to the western-style diet may reduce the risk for
      colorectal neoplasia. Using rectal epithelial proliferation (REP) measurements as
      a biomarker of response to intervention, the authors evaluated the effects of 1
      year calcium supplementation in adenoma patients and its possible interactions
      with the patients' dietary and lifestyle habits. METHODS: Consenting adenoma
      patients, without a family history of colorectal neoplasia, were randomly
      selected to receive 3.75 g calcium carbonate (1.5 g Ca2+) daily or to receive no
      treatment. All had their long-term dietary and lifestyle habits assessed and
      their REP labeling index (LI) evaluated before and at end of follow-up. The
      change in LI was compared between groups, and statistical associations were
      examined between mean nutrient consumption and treatment effect and between
      lifestyle and treatment effect. RESULTS: Fifty-two adenoma patients (33 treated
      and 19 untreated) completed intervention and follow-up. There were no significant
      differences between study groups in age, weight, cigarette smoking, or medication
      use. The LI decreased in 58% of calcium-intervened patients and in only 26% of
      nonintervened patients (P = 0.04); the mean LI x 100 (+/- standard deviation) of
      the former fell from 5.04 +/- 1.93 to 4.54 +/- 1.58, and rose from 4.32 +/- 1.58
      to 4.93 +/- 1.58 in the latter (P = 0.04). A lower fat, a higher carbohydrate,
      fiber, or fluid intake each interacted with the calcium supplementation to
      decrease the LI (P = 0.02, 0.001, 0.02, and 0.08, respectively). CONCLUSIONS:
      Long-term calcium supplements significantly suppressed REP in adenoma patients,
      and long-term dietary habits contributed to this effect. Patient diet should be
      assessed when researchers use REP as a biomarker in calcium chemoprevention
      studies. Study results indicated that relevant dietary counseling may be useful
      in addition to calcium supplements in persons at increased risk for colorectal
      neoplasia.

PMID- 11241255
TI  - Cancer risk in patients with inflammatory bowel disease: a population-based
      study.
AB  - BACKGROUND: The objective of the current study was to determine the incidence of
      cancer among persons with inflammatory bowel disease (IBD) and to compare these
      incidence rates with those of the non-IBD population using population-based data
      from the administrative claims data of Manitoba's universal provincial insurance
      plan (Manitoba Health). METHODS: IBD patients were matched 1:10 to randomly
      selected members of the population without IBD based on year, age, gender, and
      postal area of residence. The incidence of cancer was determined by linking
      records from the IBD and non-IBD cohorts with the comprehensive Cancer Care
      Manitoba registry. Incidence rates and rate ratios (IRR) were calculated based on
      person-years of follow-up (Crohn's disease = 21,340 person-years and ulcerative
      colitis [UC] = 19,665 person-years) for 1984-1997. RESULTS: There was an
      increased IRR of colon carcinoma for both Crohn disease patients (2.64; 95%
      confidence interval [95% CI], 1.69-4.12) and UC patients (2.75; 95% CI, 1.91
      3.97). There was an increased IRR of rectal carcinoma only among patients with UC
      (1.90; 95% CI, 1.05-3.43) and an increased IRR of carcinoma of the small
      intestine only in Crohn disease patients (17.4; 95% CI, 4.16-72.9). An increased
      IRR of extraintestinal tumors was observed only for the liver and biliary tract
      in both Crohn disease patients (5.22; 95% CI, 0.96-28.5) and UC patients (3.96;
      95% CI, 1.05-14.9). There was an increased IRR of lymphoma for males with Crohn
      disease only (3.63; 95% CI, 1.53-8.62), and this finding did not appear to be
      related to use of immunomodulatory therapy. Compared with controls, Crohn's
      disease was associated with an increased risk of cancer overall, but UC was not.
      CONCLUSIONS: There appear to be similar increased risks for developing colon
      carcinoma and hepatobiliary carcinoma among patients with Crohn disease and UC.
      There is an increased risk of developing rectal carcinoma in UC patients, an
      increased risk of developing carcinoma of the small bowel in Crohn disease
      patients, and an increased risk of developing lymphoma among males with Crohn
      disease.

PMID- 11241254
TI  - The Collection of Indirect and Nonmedical Direct Costs (COIN) form: a new tool
      for collecting the invisible costs of androgen independent prostate carcinoma.
AB  - BACKGROUND: There are limited data available regarding the cost of care in
      patients with androgen independent prostate carcinoma (AIPC), and there are no
      data on the impact of direct nonmedical and indirect costs (DNM/IC). This lack of
      data, along with the feasibility of collecting DNM/IC, was examined in patients
      with AIPC who took part in a randomized trial using a newly developed
      questionnaire, the Collection of Indirect and Nonmedical Direct Costs (COIN)
      form. METHODS: Patients with AIPC were randomized to one of three treatment arms:
      1) strontium only (strontium 4 Mci in Week 1 and Week 12) (STRONT); 2)
      vinblastine 4 mg/m(2) per week for 3 weeks then 1 week off and estramustine, 10
      mg/kg per day (CHEMO); or 3) a combination of treatments outlined in the arms for
      CHEMO and STRONT (CHEMO/STRONT). Direct medical costs were collected through the
      hospital billing system. DNM/IC data were obtained prospectively using the COIN
      form. Cost data were analyzed for a period of 6 months. RESULTS: Twenty-nine
      patients were randomized, after which the protocol was closed because of poor
      accrual. The median survival of the patients was 22.3 months. The mean and median
      total costs for the 20 of 29 patients with complete cost information were $12,647
      and $11,257 over 6 months, respectively. DNM/IC represented 11% of the total cost
      (range, from < 1% to 42%); in 20% of participating individuals, these costs
      accounted for 35-42% of total costs. Failure to collect complete cost information
      was due to early death, administrative difficulties, and loss to follow-up.
      CONCLUSIONS: In this pilot project, the collection of these cost data using the
      COIN form was feasible and practical and was limited primarily by logistic, not
      form specific, issues. DNM/IC were found to be a significant proportion of total
      costs (up to 42%) in selected patients, and this information proved to be a
      useful addition to the cost analysis. Approximately 98 patients would be required
      to detect a 20% difference in total costs between arms in a properly powered,
      randomized trial. Considering the potentially significant impact on total costs,
      DNM/IC data should be included in future cost-analysis studies of patients with
      AIPC and other diseases.

PMID- 11241256
TI  - Breast carcinoma presents a decade earlier in Mexican women than in women in the
      United States or European countries.
AB  - BACKGROUND: In Mexico, breast carcinoma is the second most frequent malignancy,
      representing 10.6% of all cases and 16.4% of all cancers in women, with an
      increase in breast carcinoma mortality rates from 3.6 per 100,000 women in 1985
      to 6 per 100,000 women in 1994. Most of the tumors are diagnosed in advanced
      stages with little chance of cure. METHODS: To determine the age of patients in
      Mexico at presentation of breast carcinoma, the authors analyzed the cases
      registered from 1993 to 1996 from the database of the Histopathological Registry
      of Malignant Neoplasms in Mexico. RESULTS: There were 29,075 cases of breast
      carcinoma. The median age of Mexican women with breast carcinoma is 51 years, and
      45.5% of all breast carcinomas develop before patients reach age 50 years. The
      most frequently affected age group is that of 40-49 years (29.5%), whereas the
      groups from 30 to 39 and from 60 to 69 years of age have a similar percentage
      (14%) of frequency. This contrasts with women from the United States, as well as
      with women from European countries, where the median age at presentation is 63
      years, and only one-fourth of the patients are younger than 50 years of age, and
      three-fourths are postmenopausal. Similar to Mexico, in Venezuela and in Japan
      nearly one-half of women with breast carcinoma are younger than 50 years of age,
      and this resembles rates in many Latin American countries. CONCLUSIONS: It is
      necessary to change the guidelines of breast carcinoma screening in Mexican
      women, to increase the possibility of early diagnosis and better survival.

PMID- 11241257
TI  - Equal care ensures equal survival for African-American women with cervical
      carcinoma.
AB  - BACKGROUND: [corrected] It was the purpose of this study to investigate whether
      race is an independent prognostic factor in the survival of patients with
      cervical carcinoma in a health care system with minimal racial bias, and few
      barriers to access to care. METHODS: Records for patients with a diagnosis of
      invasive cervical carcinoma from 1988 to 1999 were obtained from the Automated
      Central Tumor Registry for the United States Military Health Care System.
      Clinical data including race, age at diagnosis, histology, grade, stage,
      socioeconomic status, treatment modality, and survival also were obtained.
      Survival analysis was performed with Kaplan-Meier survival curves. RESULTS: One
      thousand five hundred fifty-three patients were obtained for review. Sixty-five
      percent of patients were Caucasian, and 35% were minorities. Of the minorities,
      29% were African Americans (AAs). Mean age of diagnosis was similar among AAs and
      Caucasians, 44 and 42 years, respectively. There was no statistically significant
      difference between the distribution of age, stage, grade, or histology between
      Caucasians and AAs. Forty-six percent of patients were treated with surgery and
      56% with radiation therapy, with no difference in type of treatment between the
      Caucasian and AA groups. Five- and 10-year survival rates for Caucasians and AAs
      were 75%, and 76%, and 64% 65% (P = 0.59), respectively. CONCLUSIONS: In an equal
      access, unbiased, nonracial environment, race is not an independent predictor of
      survival for patients with cervical carcinoma. This study has shown, for the
      first time to the authors' knowledge, that when they receive equal treatment for
      cervical carcinoma, AA women's survival can approach that of their nonminority
      counterparts (75% at 10 years).

PMID- 11241258
TI  - Evidence for an association between cutaneous melanoma and non-Hodgkin lymphoma.
AB  - BACKGROUND: Over the past 2 decades both cutaneous melanoma (CM) and non-Hodgkin
      lymphoma (NHL) incidence rates have increased substantially. One approach to
      better understanding the etiologic basis for these increases is to examine the
      risk of NHL in CM survivors and the risk of CM in NHL survivors. METHODS: To
      explore the possible association between CM and NHL, the authors followed cohorts
      of CM and NHL patients registered through the National Cancer Institute's
      Surveillance, Epidemiology, and End Results (SEER) program between 1973 and 1996
      and identified patients who developed CM after NHL and NHL after CM. The number
      of observed cases then were compared with the number of expected cases to see if
      CM survivors were at an increased risk of NHL or if NHL survivors were at an
      increased risk of CM. RESULTS: Between 1973 and 1996, 54,803 CM patients and
      62,597 NHL patients who met the authors' inclusion criteria were identified
      through SEER. The authors found statistically significant elevated risks of NHL
      among CM survivors (standardized incidence ratio [SIR], 1.42; 95% confidence
      interval [CI], 1.23-1.63) and CM among NHL survivors (SIR, 1.75; 95% CI, 1.48
      2.07). CONCLUSIONS: These results support an association between CM and NHL.
      Although detection bias and posttherapy effects may explain part of this
      association, shared genetic or etiologic factors, such as sunlight exposure, also
      may play a role.

PMID- 11241259
TI  - Clinical significance of atypical glandular cells of undetermined significance in
      postmenopausal women.
AB  - BACKGROUND: Glandular atypia in Papanicolaou (Pap) smears from postmenopausal
      women is encountered frequently. This finding can be the result of artifactual
      alterations such as drying artifacts and inflammatory changes or may represent a
      squamous or glandular, preneoplastic or neoplastic process. Therefore, it is
      important to determine the clinical implication of a diagnosis of atypical
      glandular cells of undetermined significance (AGUS) in postmenopausal patients.
      METHODS: A total of 30,036 Pap smears were obtained from postmenopausal women
      between 1995 and 1997. Among these smears, 154 (0.51%) had a diagnosis of AGUS.
      Follow-up was available for 133 patients (86.4%); 110 patients (82.7%) had
      histologic follow-up (including cervical biopsy, endocervical [EC] curettage,
      and/or endometrial [EM] biopsy) and 23 patients (17.3%) had repeat smears.
      RESULTS: Thirty-six of 110 patients (32.7%) were found to have a clinically
      significant lesion (defined as a preneoplastic or neoplastic, glandular or
      squamous lesion) on subsequent histologic follow-up. Nineteen patients (53%) had
      glandular lesions (15 EM adenocarcinoma [ACA] cases, 2 EC ACA cases, 1 EC
      adenocarcinoma is situ case, and 1 EM hyperplasia case). Seventeen patients (47%)
      had a squamous intraepithelial lesion (SIL) (6 cases of low-grade SIL, 9 cases of
      high-grade [HGIL], and 2 cases of squamous cell carcinoma). Among those patients
      with repeat Pap smears, five patients had persistent AGUS/atypical squamous cells
      of undetermined significance and one patient had an SIL. CONCLUSIONS: The
      incidence of AGUS among postmenopausal patients was similar to that of the
      general population (0.51% vs. 0.56%; P > 0.05). A significant percentage of these
      patients were found to have a clinically significant lesion on subsequent follow
      up. Furthermore, a majority of these lesions were ACA (53%) or HGSIL (26%). The
      findings of the current study strongly suggest the need for the close follow-up
      of postmenopausal patients with a diagnosis of AGUS. Cancer (Cancer Cytopathol)

PMID- 11241261
TI  - Atypical squamous metaplastic cells: reproducibility, outcome, and diagnostic
      features on ThinPrep Pap test.
AB  - BACKGROUND: Atypical squamous metaplastic (ASM) cells are associated with high
      grade squamous intraepithelial lesions (HGSIL) in many cases. The reproducibility
      of the diagnosis and biopsy follow-up results of cases designated as ASM were
      studied at Women and Infants' Hospital of Rhode Island. METHODS: Of 180 patients
      with ASM who the authors examined from January 1, 1998 to September 30, 1998, 147
      (81.7%) had subsequent biopsies. Results of the biopsies were tallied. Twenty
      cases were rescreened in a blinded fashion to determine intra- and interobserver
      agreement and to identify diagnostic features. RESULTS: Sixty-five (44.2%) cases
      of ASM had HGSIL on biopsy, 26 (17.7%) had low-grade squamous intraepithelial
      lesion, and 56 cases (38.1%) were benign. Overall individual consistency is 8 of
      16 (50%), and overall agreement is 13 of 64 (20%). CONCLUSIONS: Sixty-two percent
      of cases designated as ASM cytologically were associated with SIL, primarily
      HGSIL, at biopsies. The findings underscore the importance of this subcategory of
      atypical squamous cells. However, poor reproducibility suggests the need for
      refined criteria and/or continuing education, and obtaining second opinion.
      Cancer (Cancer Cytopathol)

PMID- 11241260
TI  - Papanicolaou smear sensitivity for the detection of adenocarcinoma of the cervix:
      a study of 49 cases.
AB  - BACKGROUND: Papanicolaou smear sensitivity for cervical adenocarcinoma (CVCA) is
      not well established. Also uncertain are the relative contributions to falsely
      negative diagnoses of sampling, screening, and interpretive errors. METHODS:
      Papanicolaou smears were identified from all patients at our institutions with
      biopsy-proven cervical adenocarcinoma from 1988-1998. All available negative and
      unsatisfactory smears were reviewed. RESULTS: Of 49 patients with CVCA, 66 smears
      initially diagnosed as negative and 4 smears initially diagnosed as
      unsatisfactory from 30 patients were identified. Thirty-two negative smears and 4
      unsatisfactory smears from 19 patients were available for review. The
      retrospective diagnoses in the cases initially called negative were:
      unsatisfactory in 2, negative in 15, and atypical glandular cells consistent with
      either adenocarcinoma in situ (AIS) or CVCA in 15. Three of four smears initially
      called unsatisfactory had neoplastic glandular cells identified retrospectively.
      The 18 falsely negative or falsely unsatisfactory smears were from 13 patients
      obtained up to 5 years before biopsy diagnosis. These smears contained neoplastic
      cells likely to have been mistaken for lower segment endometrial cells (LUS) or
      endocervical cells with tubal metaplasia (TM) in 11, reactive endocervical cells
      in 6, and both in 1. In 16 of the 18 smears, the abnormal cells were abundant,
      although preservation was suboptimal in 6. CONCLUSIONS: Sensitivity of a single
      Papanicolaou smear for CVCA was between 45% and 76% depending on the
      classification of negative slides that were not available for review, comparable
      to previously reported sensitivity for AIS. The diagnostic false-negative or
      false-unsatisfactory rate in reviewed smears was 50% (18 of 36). Diminished
      sensitivity is due to the under recognition of glandular neoplasia resembling
      LUS, TM, or reactive endocervical cells. Cancer (Cancer Cytopathol)

PMID- 11241263
TI  - Fine-needle aspiration biopsy of bronchioloalveolar carcinoma.
AB  - BACKGROUND: The purpose of the current study was to determine the accuracy of the
      cytologic diagnosis of bronchioloalveolar carcinoma (BAC) by fine-needle
      aspiration biopsy (FNAB). METHODS: During a 4-year period (1994-1998), 1664 lung
      FNABs were performed. Forty-nine patients with BAC diagnosed by FNAB and/or
      surgical biopsy formed the basis of this study. RESULTS: Twenty-four patients
      diagnosed with BAC by FNAB had histologic confirmation. Surgical pathology
      revealed BAC in 15 patients with a cytologic diagnosis of large cell carcinoma
      (LCA) or adenocarcinoma (ACA). Nine patients diagnosed with BAC by FNAB were
      found to have ACA histologically. One unsatisfactory aspirate was diagnosed as
      BAC by surgical pathology. Review of 15 FNAB specimens with a diagnosis of LCA or
      ACA revealed cytologic features typical of BAC. In six aspirates, additional
      features such as pronounced nuclear crowding and overlapping, variation in
      nuclear size, and increased number of pleomorphic cells interfered with the FNAB
      diagnosis of BAC. Nine FNABs with a diagnosis of BAC were found histologically to
      have ACA with a focal BAC growth pattern. One unsatisfactory FNAB aspirate
      diagnosed as BAC histologically was due to sampling error. CONCLUSIONS: A
      diagnosis of BAC by FNAB is possible using conventional cytologic criteria. Some
      BACs show pronounced nuclear crowding and overlapping, variation in nuclear size,
      and an increased number of pleomorphic cells cytologically, which may interfere
      with an FNAB diagnosis of BAC. FNABs from ACA cases with a focal BAC pattern
      remain a diagnostic dilemma due to the nature of the lesion. In addition,
      sampling error by FNAB can be a diagnostic pitfall. Cancer (Cancer Cytopathol)

PMID- 11241262
TI  - Small cells in cervical-vaginal smears of patients treated with tamoxifen.
AB  - BACKGROUND: "Small cells" have been described in the cervical-vaginal
      (Papanicolaou [Pap]) smears of patients receiving tamoxifen. The current study
      determined the frequency of this finding and its implications for the
      differential diagnosis. METHODS: A computer-based search of the cytopathology
      files from January 1994 to December 1998 was performed for Pap smears from
      patients with a history of tamoxifen treatment. All smears were reviewed for the
      presence of "small cells" and endometrial cells. Pap smears from an age-matched
      control group that was not treated with tamoxifen also were screened for "small
      cells." RESULTS: Five hundred forty-eight Pap smears were identified from 425
      patients (mean age, 62 years; average duration of treatment, 43 months). Clusters
      of these "small cells" were present in 104 Pap smears from 86 patients (19%). The
      background pattern was proliferative in the majority of the Pap smears (83%). In
      five Pap smears (5%), these "small cells" were interpreted originally as
      endometrial cells. In the remaining Pap smears, no reference to the presence of
      the cells was made in the original report. "Small cells" were identified in 79
      Pap smears (18%) in the control group (n = 443 smears). CONCLUSIONS: The
      incidence of "small cells" is similar in the Pap smears of patients with or
      without a history of tamoxifen treatment. These cells are similar to reserve
      cells noted in atrophic smears. However, as a result of the proliferative effect
      of tamoxifen in the cervical epithelium, these cells are prominent when admixed
      with superficial and intermediate cells in patients treated with tamoxifen. These
      cells need to be differentiated from endometrial cells to avoid unnecessary
      follow-up procedures. Cancer (Cancer Cytopathol)

PMID- 11241264
TI  - Soft tissue aspiration cytopathology of malignant lymphoma and leukemia.
AB  - BACKGROUND: Malignant lymphoma (ML) and leukemia infrequently involve soft tissue
      and, to the authors' knowledge few reports exist regarding the role of fine
      needle aspiration biopsy (FNAB) in their diagnosis. In the current study, the
      authors report their experience with FNAB in patients with soft tissue ML and
      leukemia. METHODS: All cases of ML, leukemia, or atypical lymphoid cells from
      soft tissue aspirates were reviewed. Masses from lymph node-rich sites, those
      adjacent to enlarged lymph nodes, or those associated with cutaneous lesions were
      excluded. RESULTS: Twenty-one patients (male:female ratio of 1:1) who ranged in
      age from 10 months to 87 years (mean age, 51 years) were studied. Seven patients
      had superficial masses and 14 patients had deep soft tissue masses. Sites
      included the extremities (10 patients), trunk (8 patients), and head (3
      patients). Cytologic diagnoses were ML (large cell [11 patients] and Hodgkin [1
      patient]), acute leukemia (lymphoblastic [3 patients] and myelogenous [2
      patients]), and atypical lymphoid cells (4 patients). Eight aspirates represented
      the initial diagnosis of ML, three were recurrent ML, four were recurrent
      leukemia, one was initial leukemia, and one ML aspirate was obtained concurrently
      with core needle biopsy. Four aspirates were diagnosed as atypical lymphoid
      cells. Three subsequently were diagnosed as ML and one aspirate was diagnosed as
      acute leukemia. All ML were of large B-cell type. One case of atypical lymphoid
      cells was found to be a mantle cell lymphoma. The leukemia cases were T-cell (two
      cases), pre-B-cell (two cases), and myelogenous (two cases). Immunophenotyping
      confirmed the cytology by flow cytometry (five cases), cytospin (three cases),
      and cell block (four cases). Immunophenotyping of eight cases was performed on
      tissue samples. In one case a cytopathologic diagnosis of ML reversed a prior
      tissue core biopsy diagnosis of liposarcoma. The specificity and sensitivity
      rates for a definitive diagnosis of ML or leukemia were 100% and 82%,
      respectively. CONCLUSIONS: In the majority of cases, it is possible to determine
      a specific diagnosis and subtype of soft tissue ML or leukemia using FNAB. Cancer
      (Cancer Cytopathol)

PMID- 11241265
TI  - Chordoma: a cytologic study with histologic and radiologic correlation.
AB  - BACKGROUND: Chordoma is a rare malignant tumor of fetal notochord origin that
      occurs along the spinal axis. The fine-needle aspiration biopsy (FNAB) findings
      are described, correlated with histology and radiology, and compared with
      previously reported descriptions of chordoma. METHODS: Fine-needle aspiration
      biopsies of 12 cases of chordoma with histologic confirmation were reviewed.
      Imaging studies were reviewed in seven cases. Cytologic material included smears,
      ThinPrep, and cell blocks. Immunostains were performed on selected cytologic and
      histologic specimens. Multiple cytologic parameters were studied. RESULTS: Eleven
      specimens were from the spinal axis, and one was from a chest wall metastasis.
      Ten cases were diagnosed as chordoma on cytologic material, one was positive for
      malignancy with a differential diagnosis of chordoma and well differentiated
      chondrosarcoma, and one was positive for malignancy, not further classified. Most
      smears were moderately to highly cellular and demonstrated typical physaliphorous
      cells and a myxoid background. Two of the 10 cases diagnosed as chordoma showed
      pleomorphic physaliphorous cells, nuclear inclusions, and binucleation. Nuclear
      inclusions were observed in three other cases diagnosed as chordoma. Histologic
      follow-up of one case with pleomorphic physaliphorous cells showed conventional
      chordoma with focal areas of increased cellularity and pleomorphism. Pleomorphic
      sarcomatous cells were the predominant cell type in one case that showed
      dedifferentiated chordoma histologically. Mitotic figures were rarely observed in
      cytologic material. CONCLUSIONS: Cytomorphologic features of chordoma allow
      accurate diagnosis by FNAB. Features associated with dedifferentiation include
      increased pleomorphism of physaliphorous cells and may include nuclear
      inclusions, bi- or multinucleation, and rarely, mitotic figures. Cancer (Cancer
      Cytopathol)

PMID- 11241266
TI  - Fine-needle aspiration cytology of Hodgkin disease: a study of 89 cases with
      emphasis on false-negative cases.
AB  - INTRODUCTION. Although the cytologic features of Hodgkin disease (HD) has been
      well described, HD accounts for most of the false-negative fine-needle aspiration
      (FNA) biopsies of malignant lymphomas. In this study, the authors examined the
      factors contributing to a false-negative diagnosis of HD. METHODS: Eighty-nine
      cases from 72 patients (23 females and 49 males) with HD evaluated by FNA were
      identified between 1990 and 1999. The patients' ages ranged from 5 to 90 years
      (median, 38 years). Eighty-five FNAs were from lymph nodes, and 4 were from
      extranodal sites. Histologic correlation was available for all patients. RESULTS:
      Based on the original cytologic diagnosis, 43 (48.3%) cases had a positive
      diagnosis of HD, 20 (22.5%) suspicious or atypical diagnosis, 13 (14.6%) a benign
      diagnosis (false-negative cases), and 10 (11.2%) were nondiagnostic. Three (3.4%)
      additional cases had a malignant diagnosis other than HD. After review, three
      false-negative cases were reclassified as HD and seven as atypical lymphoid
      proliferation. Three of these 10 cases also showed conspicuous collections of
      histiocytes mimicking poorly formed granulomas. In those "atypical" cases, only
      rare Reed-Sternberg (R-S) cells variants were identified. No R-S cells or its
      variants were identified in the remaining three false-negative cases; subsequent
      excisional biopsy showed partial involvement of the lymph node by HD in two
      cases. Among the nondiagnostic cases, nine cases showed considerable fibrosis in
      the resected lymph node. In addition, six cases were performed without on-site
      assessment. CONCLUSIONS: The cytologic diagnosis of HD can be challenging when
      classic R-S cells are absent. Contributing factors for a false-negative diagnosis
      include obscuring reactive inflammatory cells, fibrosis of the involved lymph
      nodes, partial involvement of the lymph node by HD, sampling error, and
      misinterpretation. On-site assessment significantly minimizes the false-negative
      diagnostic rate. Furthermore, additional material can be obtained for ancillary
      studies. Cancer (Cancer Cytopathol)

PMID- 11241267
TI  - The cytomorphology of ocular surface squamous neoplasia by using impression
      cytology.
AB  - BACKGROUND: The term ocular surface squamous neoplasia (OSSN) encompasses
      conjunctival and corneal intraepithelial neoplasia through to invasive squamous
      cell carcinoma of the ocular surface. The disease is related to prolonged
      exposure to solar ultraviolet light and has been proposed as an acquired immune
      deficiency syndrome-associated tumor. To the authors' knowledge, very few reports
      describing the cytology of these lesions have been published. METHODS: Impression
      cytology (IC) samples collected from the eyes of patients with a range of ocular
      surface diseases were available for study. From these, 267 sets of impressions
      had subsequent histopathology that had been collected within 6 months of the IC,
      and which indicated the presence of OSSN. The IC from these cases was used to
      describe the cytomorphology of intraepithelial and invasive OSSN. RESULTS: Within
      the intraepithelial group, keratinized dysplastic cells that often were
      accompanied by hyperkeratosis, syncytial-like groupings, and nonkeratinized
      dysplastic cells were described. Within the invasive group, cases with
      significant keratinization and an additional group of cases with little
      keratinization and sometimes also prominent macronucleoli were described.
      Keratinized cases were the most numerous in both the intraepithelial and invasive
      groups. A description also was given of a low number of cases with cytology and
      also subsequent histopathology indicating the presence of intraepithelial OSSN,
      in the absence of a clinically detectable lesion. CONCLUSIONS: This detailed
      description of the cytomorphology of a high number of cases of OSSN with
      confirmation by histopathology should assist others with little experience of the
      cytology of these lesions to examine them with increased confidence. Cancer
      (Cancer Cytopathol)

PMID- 11241268
TI  - Immunocytochemistry in the differential diagnosis of serous effusions: a
      comparative evaluation of eight monoclonal antibodies in Papanicolaou stained
      smears.
AB  - BACKGROUND: The distinction between pleural mesothelioma (MS), reactive
      mesothelium (RM), and adenocarcinoma (AC) in serous effusions continues as a
      diagnostic problem in pathology. Immunohistochemistry can help, especially in
      surgical samples, but the optimum panel of antibodies has yet to be reported. The
      application of these antibodies to serous effusions has displayed variable
      results. The aim of this study was to evaluate the usefulness of eight monoclonal
      antibodies in the differential diagnosis of MS, RM, and AC in serous effusions.
      METHODS: A total of 44 cytologic specimens of serous effusions (26 pleural, 15
      peritoneal, and 3 pericardial) from 30 ACs, 3 MSs, and 11 RMs, previously stained
      with Papanicolaou stain, were selected retrospectively from our files and stained
      with HBME-1, thrombomodulin, calretinin, MOC-31, Ber-EP4, E-cadherin, CEA, and CD
      15. The immunoreactions were evaluated independently by two pathologists. A
      stepwise logistic regression analysis was applied to the data to select an
      appropriate panel of antibodies. RESULTS: Statistical significance was found with
      HBME-1, thrombomodulin, MOC-31, Ber-EP4, and CD-15, when comparing both AC versus
      MS, and AC versus any type of mesothelial proliferation (MS or RM). Using HBME-1,
      80% of ACs were negative whereas all three MSs reacted strongly with P = 0.003. A
      P = 0.02 was reached with thrombomodulin with 76.5% of ACs showing no
      immunoreactivity. Ber-EP4 and MOC-31 displayed good results with a P < 0.001 and
      0.01, respectively. CD-15 reached a P = 0.034. No differences were found using
      the other antibodies. Ten ACs, all 3 MSs, and 10 RMs were double immunostained
      with HBME-1 and/or MOC-31 and Ber-EP4 successfully. CONCLUSIONS:
      Immunohistochemical studies performed on Papanicolaou stained cytologic smears
      proved to be useful in the differentiation between metastatic AC and mesothelial
      proliferation. HBME-1, thrombomodulin, MOC-31, Ber-EP4, and CD-15 were the most
      useful. In selected cases, it appeared that double immunostaining aided the
      differential diagnosis. Cancer (Cancer Cytopathol)

PMID- 11241269
TI  - Expression of the RNA component of human telemorase (hTR) in ThinPrep
      preparations from bladder washings.
AB  - BACKGROUND: The enzyme telomerase is associated with cellular immortality and is
      expressed in the vast majority of human neoplasms. The expression of the RNA
      component of human telomerase (hTR) shows excellent concordance with enzyme
      activity. METHODS: In this study, hTR expression was analyzed in a series of 18
      perioperative bladder washings and compared with histologic diagnoses from
      material obtained in the same setting. The hTR expression analysis used an 35S
      based in-situ hybridization assay. ThinPrep preparations fixed in PreservCyt
      solution (Cytyc Corporation, Boxborough, MA) were hybridized with sense and
      antisense hTR probes. A 1-4+ grading scheme was used, with appropriate positive
      and negative controls. RESULTS: Five of six (83%) lesions with benign histology
      had hTR expression that was 2+ or less in the exfoliated urothelial cells. In
      contrast, 11 of 12 (93%) lesions with malignant histology had an hTR expression
      that was focally 3+ or more, with 7 of 12 (58%) lesions having 4+ hTR expression
      in at least some urothelial clusters. Although increased hTR expression was
      present in smears with malignant urothelial cells, a similar trend was not seen
      with muscularis propria invasion or higher grades of TCC on subsequent histology.
      CONCLUSIONS: The use of in situ hybridization technique bypasses the need for
      stringent specimen processing and allows identification of the specific cell type
      that expresses telomerase. Cancer (Cancer Cytopathol)

PMID- 11241270
TI  - High viral burden in the presence of major HIV-specific CD8(+) T cell expansions:
      evidence for impaired CTL effector function.
AB  - To investigate the effect of HIV-specific CD8(+) T cells on viral plasma load and
      disease progression, we enumerated HLA-A2-, B8- and B57-restricted CD8(+) T cells
      directed against several HIV epitopes in a total of 54 patients by the use of
      tetrameric HLA-peptide complexes. In patients with high CD4(+) T cell numbers,
      HIV-specific tetramer(+) cells inversely correlated with viral load. Patients
      with CD4(+) T cell numbers below 400/microl blood, however, carried high viral
      load despite frequently having high tetramer(+) T cell numbers. This lack of
      correlation between viral load and tetramer(+) cells did not result from viral
      escape variants, as in only 4 of 13 patients, low frequencies of viruses with
      mutated epitopes were observed. In 15 patients we measured CD8(+) T cell antigen
      responsiveness to HIV peptide stimulation in vitro. FACS analyses showed
      differential IFN-gamma production of the tetramer(+) cells, and this proportion
      of IFN-gamma-producing tetramer(+) cells correlated with AIDS-free survival and
      with T cell maturation to the CD27(-) effector stage. These data show that most
      HIV-infected patients have sustained HIV-specific T cell expansions but many of
      these cells seem not to be functional, leaving the patient with high numbers of
      non-functional virus-specific CD8(+) T cells in the face of high viral burden.

PMID- 11241271
TI  - Regeneration and tolerance factor of the human placenta induces IL-10 production.
AB  - Regeneration and tolerance factor (RTF) was originally identified in the placenta
      of mice and the isolated protein shown to have suppressive effects. In these
      studies, the gene cloned from thymus tissue was mapped to human chromosome 12.
      The role of recombinant RTF on cytokines was examined. In addition, we examined
      the human placenta by immunohistochemistry for RTF expression. RTF was expressed
      at the peripheral layer of cytotrophoblast in 7-9-week-old placentas. Using the
      RTF gene sequence, a recombinant protein was prepared and shown to induce IL-10
      production. These data indicate that RTF is expressed by the tissues most
      intimately involved at the maternal-fetal interface, and its biological activity
      is capable of producing the necessary immune response for initiating and
      maintaining the maternal-fetal relationship.

PMID- 11241272
TI  - Removal of the circumsporozoite protein (CSP) glycosylphosphatidylinositol signal
      sequence from a CSP DNA vaccine enhances induction of CSP-specific Th2 type
      immune responses and improvesprotection against malaria infection.
AB  - The C terminus of the circumsporozoite protein (CSP) is anchored to the parasite
      cell membrane by a glycosylphosphatidylinositol (GPI) glycolipid. This GPI signal
      sequence functions poorly in heterologous eukaryotic cells, causing CSP retention
      within internal cell organelles during genetic immunization. Cellular location of
      antigen has quantitative and qualitative effects on immune responses induced by
      genetic immunization. Removal of the GPI signal sequence had a profound effect on
      induction and efficacy of CSP-specific immune response after genetic immunization
      of BALB/c mice with a gene gun. The CSP produced from the plasmid lacking the GPI
      anchor signal sequence (CSP-A) was secreted and soluble, but that produced by the
      CSP+A plasmid was not. The CSP-A plasmid induced a highly polarized Th2 type
      response, in which the CSP-specific IgG antibody titer was three- to fourfold
      higher, and the protective effect was significantly greater than that induced by
      the CSP+A plasmid. Thus, these two physical forms of CSP induced quantitatively
      and qualitatively different immune responses that also differed in protective
      efficacy. Engineering plasmid constructs for proper cellular localization of gene
      products is a primary consideration for the preparation of optimally efficacious
      DNA vaccines.

PMID- 11241273
TI  - Rapid inactivation of stromal cell-derived factor-1 by cathepsin G associated
      with lymphocytes.
AB  - The CXC chemokine stromal cell-derived factor (SDF)-1 is produced constitutively
      in different tissues. It is the only known ligand for CXCR4, which is widely
      expressed in leukocytes and in some tissue cells, and acts as coreceptor for X4
      HIV strains. Because of the general interest in the mechanisms that regulate the
      activity of constitutively expressed chemokines, we have studied the inactivation
      of SDF-1 in cells that bear CXCR4. Here we show that B lymphocytes, NK cells and,
      to a lesser extent, T lymphocytes inactivate SDF-1 by N-terminal processing.
      Inactivation is due to cathepsin G which is associated with the membrane of
      lymphocytes and rapidly cleaves off five N-terminal residues by acting on the
      Leu(5)-Ser(6) bond yielding SDF-1(6-67). Processing was observed with intact
      cells, cell membrane preparations and soluble cathepsin G obtained by extraction
      of the membranes with Triton X-100. Cathepsin G is released by neutrophils and
      monocytes and binds on the surface of lymphocytes by an apparently saturable
      process. Analysis of the product obtained, the time course and the sensitivity to
      inhibitors shows that cathepsin G is the only protease involved. Conversion of
      SDF-1 to SDF-1(6-67) was complete within minutes to 1-2 h depending on the enzyme
      source, and was abrogated by inhibitors of serine proteases and chymostatin.
      Diprotin A, an inhibitor of dipeptidyl peptidase IV, was without effect. Owing to
      its availability on the surface of SDF-1-responsive cells and its rapid effect,
      cathepsin G is likely to play a significant role in down-regulating SDF-1
      activity.

PMID- 11241274
TI  - Frequent recognition of BCRF1, a late lytic cycle protein of Epstein-Barr virus,
      in the HLA-B*2705 context: evidence for a TAP-independent processing.
AB  - Using a transient COS transfection assay, allowing a rapid estimation of the
      dominant CD8(+) T cell responses against a large number of HLA/viral protein
      combinations within polyclonal cell lines, we searched for HLA-B*2705-restricted
      CD8 T cell responses to Epstein-Barr virus (EBV) within T cell samples enriched
      for EBV-reactive cells. Among the 18 EBV proteins tested, only 2, the latent
      protein EBNA3A and the late lytic protein BCRF1 (viral IL-10), appeared dominant
      in the B27 context, as they triggered significant TNF and cytolytic responses in
      some donors. We provide evidence that the B27/BCRF1 epitope (RRLVVTLQC) is
      located in the signal sequence and that it can be presented in a TAP-independent
      manner. Using B27/BCRF1 monomeric complexes coated on immunomagnetic beads, we
      sorted out BCRF1-specific CD8 T cells from 8 of 15 HLA-B27(+) donors. This is, to
      our knowledge, the first demonstration of a recognition of BCRF1, suggesting that
      some immune control against EBV exists even during the late stage of the lytic
      cycle. This result also strengthens the unusual ability of HLA-B*2705 to present
      peptide in a TAP-independent manner.

PMID- 11241275
TI  - Profiling the immune response in patients with breast cancer by phage-displayed
      cDNA libraries.
AB  - Display on the surface of filamentous phages has been shown to be well suited for
      the enrichment of serum antibody-binding ligands. Here, we have taken the
      advantage of this technology to analyze the humoral immune response in patients
      with cancer. The cDNA repertoires from breast cancer cell lines T47D and MCF-7
      were fused to the 3'-end of the filamentous phage M13 gene VI in all three
      reading frames. When the libraries were biopanned on rabbit polyclonal IgG
      against the human Bcl-x(L) protein, positive clones were selected, thus
      confirming the utility of the libraries. Using serum antibodies from patients
      with breast cancer, we specifically selected IgG-binding phage-encoded cDNA
      products. Sequence analysis of the selected clones identified important antigens
      including p53, centromere-F, int-2, pentraxin I, integrin beta5, cathepsin L2 and
      S3 ribosomal protein. The selected phage-displayed cDNA products were recognized
      by a significant number of breast cancer sera as compared to sera from normal
      individuals. Although the human pentraxin I mRNA was reported to be exclusively
      localized in the nervous system, we found it also expressed by breast cancer cell
      lines. Four out of 30 patients with breast cancer (13 %) showed reactivity with
      the recombinant pentraxin expressed in Escherichia coli, while no reactivity was
      found in normal sera. The obtained results demonstrate that phage display could
      be a valuable method for the identification of antigens recognized by the humoral
      immune system in patients with cancer.

PMID- 11241276
TI  - Virus infection induces proteolytic processing of IL-18 in human macrophages via
      caspase-1 and caspase-3 activation.
AB  - There is increasing evidence that IL-18 is a key pro-inflammatory cytokine and an
      important mediator of Th1 immune response. The main source of IL-18 is macrophage
      like cells. In the present study we have investigated IL-18 protein expression in
      primary human macrophages in response to influenza A and Sendai virus infections.
      Macrophages constitutively expressed proIL-18 but produced biologically active IL
      18 only after virus infection. The IL-18 release was due to virus infection
      induced proteolytic processing of 24-kDa proIL-18 into its mature 18-kDa form.
      ProIL-18 processing required active caspase-1 enzyme and the release of mature IL
      18 was blocked with a caspase-1-specific inhibitor. Caspase-3 inhibitor also
      reduced IL-18 production in response to virus infection. Inactive proforms of
      caspase-1 and caspase-3 were basally expressed in macrophages, and virus
      infection induced the cleavage of procaspases into their mature forms. Besides
      increasing the expression of caspase proteins, virus infection enhanced caspase
      mRNA expression in macrophages. The enhancement of caspase gene expression was
      abrogated by anti-IFN-alpha antibody. Furthermore, IFN-alpha and IFN-gamma could
      induce caspase gene expression. These results imply that interferons are involved
      in virus-induced caspase activation that leads to proIL-18 processing and
      subsequent release of mature IL-18.

PMID- 11241277
TI  - Increased expression of type 2 cytokines in chronic proliferative dermatitis
      (cpdm) mutant mice and resolution of inflammation following treatment with IL-12.
AB  - Chronic proliferative dermatitis (cpdm) is a spontaneous mutation that results in
      eosinophilic inflammation in multiple tissues, including the skin. To determine
      the mechanisms underlying the eosinophilic inflammation, the expression of
      cytokines in the skin was determined. There was increased expression of IL-4, IL
      5, IL-13, and granulocyte-macrophage colony-stimulating factor in the skin of
      cpdm/cpdm mice, and no change in IL-10 and TNF expression. Supernatants of
      cultured spleen cells of cpdm/cpdm mice contained an increased amount of IL-5 and
      IL-13, and a decreased amount of IFN-gamma. The ability of the cpdm/cpdm mice to
      mount a delayed-type hypersensitivity response was greatly reduced. These data
      are consistent with impaired type 1 and excessive type 2 cytokine production in
      cpdm/cpdm mice. The significance of this imbalanced cytokine production was
      evident in the efficacy of systemic treatment of cpdm/cpdm mice with IL-12.
      Mutant mice treated for 3 weeks with IL-12 had minimal changes in the skin as
      opposed to the severe dermatitis in mice treated with the vehicle. Treatment with
      IL-11, which opposes the effect of IL-12, had no effect.

PMID- 11241278
TI  - DNase I mediates internucleosomal DNA degradation in human cells undergoing drug
      induced apoptosis.
AB  - Internucleosomal DNA fragmentation following the activation of endonucleases is
      the common end point of apoptosis. DNase I, a Ca(2+) / Mg(2+)-dependent
      endonuclease ubiquitously expressed in mammalian tissues, is believed to play a
      role in this process. To analyze the in vivo function of this enzyme in human
      cells, we have generated a cell line with targeted disruption of the DNase I
      gene, as well as several stable cell lines which overexpress the DNase I gene.
      Inactivation of the human DNase I gene was obtained in the Jurkat T cell clone
      JA3, characterized by high susceptibility to apoptotic cell death induced by
      pharmacological stimuli. JA3 cells, after disruption of the DNase I gene, became
      resistant to apoptotic stimuli. DNase I was overexpressed in the human cell lines
      JA3, K562 (erythroleukemia), M 14 (melanoma) and CEM (T cell lymphoma).
      Remarkably, stable overexpression of DNase I gene resulted in accelerated
      apoptosis in JA3 cells and induced apoptosis in K562, CEM and M14 cell lines,
      which are otherwise resistant to internucleosomal DNA degradation following
      pharmacological stimuli. Our study provides the first in vivo evidence that DNase
      I mediates internucleosomal DNA degradation in human cells undergoing drug
      induced apoptosis.

PMID- 11241279
TI  - In vitro stimulation of human tonsillar subepithelial B cells: requirement for
      interaction with activated T cells.
AB  - Human tonsillar subepithelial B cells, which are a marginal zone-equivalent B
      cell subset, respond readily to T-independent type 2 antigens, but not to
      polyclonal B cell activators in vitro. In this study, subepithelial (SE) B cells
      were induced to proliferate and mature into plasma cells when co-cultured with
      activated T cells. The response of SE B cells was not observed when co-cultures
      were carried out in transwell chambers or in the presence of blocking anti-LFA-1
      antibodies, demonstrating the need for a close T-B cell interaction. The presence
      of soluble CD40 also prevented the B cell response in vitro suggesting a pivotal
      role of CD40-CD40 ligand interactions. The data are discussed in terms of the T
      cell dependence of marginal zone (MZ) B cell response and the possible existence
      of various MZ B cell subsets.

PMID- 11241280
TI  - Memory phenotype CD8(+) T cells in IL-15 transgenic mice are involved in early
      protection against a primary infection with Listeria monocytogenes.
AB  - We recently constructed IL-15 transgenic (Tg) mice using cDNA encoding a
      secretable isoform of the IL-15 precursor protein under the control of an MHC
      class I promoter. The IL-15 Tg mice exhibited resistance against a primary
      infection with Listeria monocytogenes. The numbers of memory CD8(+) T cells were
      markedly increased in the IL-15 Tg mice following Listeria infection accompanied
      by sustained IL-15 production. The increased CD44(+)CD8(+) T cells in the
      infected IL-15 Tg mice were not specialized to recognize Listeria-specific
      antigen but produced a large amount of IFN-gamma in response to bystander
      stimulation exogenous IL-15 in combination with IL-12. Furthermore, Listeria
      specific Th1 response by CD4(+) T cells was significantly augmented in the IL-15
      Tg mice compared with control mice following Listeria infection. In vivo
      depletion of the CD8(+) T cells by anti-CD8 monoclonal antibody and adoptive
      transfer of the T cells from naive IL-15 Tg mice indicated that the CD8(+) T
      cells functioned not only to eliminate bacteria at the early stage of infection
      but also to promote Th1 response to L. monocytogenes. Overexpression of IL-15
      shed light on a novel role of memory CD8(+) T cells in early protection and
      promotion of Th1 response against a primary infection with L. monocytogenes.

PMID- 11241281
TI  - Prominent T cell response to a selectively in vivo expressed Borrelia burgdorferi
      outer surface protein (pG) in patients with Lyme disease.
AB  - Diagnosis of Lyme disease by analysis of T cell immune responses in vitro is
      curtailed by poor correlation between test results and status of infection. This
      is probably due to the inherent nonspecific activation potential of the causative
      agent, the spirochete Borrelia burgdorferi, for bystander lymphocytes, in
      particular via their outer surface lipoproteins. We have now applied a novel
      protocol to determine specific T cell responses in Lyme disease patients and
      exclude unrelated cellular responses in vitro. Non-lipidated spirochetal antigens
      (OspA, OspC and P39) including those selectively expressed in the mammalian host
      (pG and BapA) were used for antigenic stimulation and autologous dendritic cells
      served as antigen-presenting cells. The majority of patients with well-defined
      early and late manifestations of Lyme disease exhibited specific T cell
      proliferative responses to one or more of the indicated antigens, however at
      distinct levels. Most notably, among the five antigens tested, pG was
      specifically recognized by the majority of T cell populations (>70%) - mainly Th1
      cells - from patients but not control individuals. These data indicate a causal
      relationship between B. burgdorferi infection and T cell reactivity to pG, thus
      making this protein a promising additional diagnostic marker for Lyme disease.

PMID- 11241282
TI  - Modulation of CD45 tyrosine phosphatase activity by antigen.
AB  - CD45 is a widely distributed phosphatase which modulates the activity of Lck by
      controlling the phosphorylation status of two tyrosine residues localized in the
      catalytic activation loop and in the negative regulatory domain. Little is known
      about the regulation of CD45 activity upon T cell activation. In the present
      study, we found that, in resting lymphocytes, an enzymatically active fraction of
      CD45 molecules is associated to the CD4 coreceptor. TCR engagement by an agonist
      ligand markedly inhibited this pool of CD45 phosphatase without affecting the CD4
      / CD45 association. These results reveal that the modulation of the CD4
      associated CD45 phosphatase activity is a very early biochemical event triggered
      by TCR stimulation. Since the recruitment of CD4 is an initial step in the
      activation process, the inhibition of this pool of CD45 molecules would be
      crucial to prevent dephosphorylation of relevant substrates which promote the
      activation process.

PMID- 11241283
TI  - Cloning and characterization of a novel mouse myeloid DAP12-associated receptor
      family.
AB  - The presence of a negatively charged residue in the transmembrane domain of DAP12
      precludes its cell surface expression in the absence of a partner receptor
      containing a positive charge in its transmembrane domain. We utilized this
      property of DAP12 to screen a BALB / c macrophage cDNA library for novel
      molecules that induce cell surface expression of DAP12. By this method, we cloned
      a cell surface receptor with a single Ig (V) domain, a transmembrane lysine
      residue, and a short cytoplasmic domain. By homology screening of BALB / c
      macrophage libraries, we identified a second cDNA for a highly homologous
      receptor. These receptors appear to be the mouse orthologues of a recently
      identified human cDNA, TREM-2, so we have designated the receptors as mouse TREM
      2a and TREM-2b. By Northern blotting, transcripts for TREM-2 were found in each
      of three macrophage cell lines but not in a variety of other hematopoietic cell
      lines. We further demonstrate that TREM-2a is associated with endogenous DAP12 in
      macrophage cells, and cross-linking of TREM-2a on the surface of macrophages
      leads to the release of nitric oxide. Our studies define TREM-2 as a receptor
      family in mouse macrophages and demonstrate the capacity of these receptors to
      activate macrophage function through DAP12.

PMID- 11241284
TI  - Interleukin-1beta costimulates interferon-gamma production by human natural
      killer cells.
AB  - Natural killer (NK) cells are an early source of immunoregulatory cytokines
      during the innate immune response to viruses, bacteria, and parasites. NK cells
      provide requisite IFN-gamma to monocytes for the elimination of obligate
      intracellular pathogens. IL-1beta is a pro-inflammatory cytokine produced by
      monocytes (i.e. a monokine) during the early immune response to infection, but
      its role in promoting human NK cell IFN-gamma production is unknown. The current
      study examines the ability of the monokine IL-1beta, plus IL-12, to costimulate
      IFN-gamma production by resting CD56(bright) and CD56(dim) human NK cell subsets.
      CD56(bright) NK cells stimulated with IL-1beta plus IL-12 produced abundant IFN
      gamma protein, while little IFN-gamma was produced in identical cultures of
      CD56(dim) cells. In addition, upon activation with IL-1beta, CD56(bright) NK
      cells exhibited considerably greater phosphorylation of extracellular signal
      regulated kinases p42/44 as compared to CD56(dim) NK cells. Quantitative PCR
      analysis showed brisk induction of IFN-gamma gene expression following
      costimulation with IL-1beta plus IL-12 in CD56(bright) NK cells, but
      intracellular flow cytometry revealed that only a fraction (42+/-2.3%) of
      CD56(bright) NK cells account for this high IFN-gamma production. These data
      suggest that the monokine IL-1beta is a potent costimulus of IFN-gamma production
      by a subset of NK cells following infectious insult.

PMID- 11241285
TI  - Thymic export in aged sheep: a continuous role for the thymus throughout pre- and
      postnatal life.
AB  - A diverse repertoire among peripheral T cells is established in early life by
      thymic export when the naive T cell pool is first formed. In contrast, during
      adult life the thymus has been thought to play only a minor role in T cell
      homeostasis. As individuals age there is an increasing proportion of peripheral T
      cells bearing a memory phenotype, as well as a corresponding decrease in the
      number of naive T cells. The change in the composition of the peripheral T cell
      pool with age is thought to occur as a result of reduced or completely curtailed
      thymic export following thymic involution at puberty together with the antigen
      driven expansion of naive T cells in the periphery. We examined thymic export
      throughout life in fetal, neonatal and aged sheep. We found that the thymus in
      adult animals showed an efficiency of production and export on a per gram basis
      equivalent to that observed for much younger animals, and continued to export
      substantial numbers of T cells long after puberty. The data demonstrate that
      naive T cells constantly enter the peripheral T cell pool at the same rate
      throughout fetal, neonatal and adult life, and that one in every 50 T cells in
      the peripheral lymphoid tissues of aged sheep had emigrated from the thymus in
      the previous 24 h. The data suggest that restoration by the thymus of a normal
      peripheral T cell repertoire in chronic T cell-depleting conditions should be
      possible in adult patients, provided the thymus is not damaged by disease or
      therapy.

PMID- 11241286
TI  - Dendritic cells as a major source of macrophage-derived chemokine/CCL22 in vitro
      and in vivo.
AB  - Macrophage-derived chemokine (MDC)/CCL22 is a CC chemokine active on dendritic
      cells (DC), NK cells and Th2 lymphocytes. The present study was aimed at
      comprehensively investigating MDC production in vitro and in vivo. DC were the
      most potent producers of MDC among leukocytes tested. Endothelial cells did not
      produce MDC under a variety of conditions. Signals that induce maturation
      (lipopolysaccharide, IL-1, TNF, CD40 ligand, recognition of bacteria and yeast)
      dramatically augmented MDC production, and dexamethasone and vitamin D3 blocked
      it. Prostaglandin E(2), which blocked the acquisition of IL-12 production and the
      capacity to promote Th1 generation, did not affect MDC production. Using mass
      spectrometry-based techniques, DC supernatants were found to contain N-terminally
      truncated forms of MDC [MDC(3-69), MDC(5-69) and MD(C7-69)] as well as the full
      length molecule. In vivo, CD1a(+), CD83(+), MDC(+) DC were found in reactive
      lymph nodes, and in Langerhans' cell histiocytosis. Skin lesions of atopic
      dermatitis patients showed that CD1a(+) or CD1b(+) DC, and DC with a CD83(+)
      phenotype were responsible for MDC production in this Th2-oriented disorder.
      Thus, DC are the predominant source of MDC in vitro and in vivo under a variety
      of experimental and clinical conditions. Processing of MDC to MDC(3-69) and
      shorter forms which do not recognize CCR4 is likely to represent a feedback
      mechanism of negative regulation.

PMID- 11241287
TI  - Anti-CD81 activates LFA-1 on T cells and promotes T cell-B cell collaboration.
AB  - CD81 is expressed on human T cells at all stages of development. CD81 is
      physically associated with CD4 and CD8 and antibodies against CD81 generate
      signals which influence thymocyte adhesion and proliferation. Here we evaluate
      the function of CD81 on mature T cells. We employ a system in which B cells
      present superantigen to autologous T cells and find that anti-CD81 promotes T
      cell-B cell collaboration. Anti-CD81 induces T cell-B cell adhesion of peripheral
      blood lymphocytes which is partially mediated by LFA-1. CD81 engagement promotes
      LFA-1-dependent T cell activation, IL-2 production and proliferation. The
      antibody 5A6 was uniquely potent in exerting these effects compared to another
      antibody to CD81 or to antibodies that react with other tetraspanins expressed on
      T cells, anti-CD53 or anti-CD82. CD81-derived signals rapidly induce high-avidity
      LFA-1 as measured by cell binding to recombinant ICAM-3-coated fluorescent
      microspheres or by cell adhesion to ICAM-3-coated plastic. 5A6 activation of LFA
      1 does not expose the high-affinity conformation epitope recognized by monoclonal
      antibody 24.

PMID- 11241288
TI  - Within the hemopoietic system, LAR phosphatase is a T cell lineage-specific
      adhesion receptor-like protein whose phosphatase activity appears dispensable for
      T cell development, repertoire selection and function.
AB  - Expression of the receptor-type tyrosine phosphatase LAR was studied in cells of
      the murine hemopoietic system. The gene is expressed in all cells of the T cell
      lineage but not in cells of any other hemopoietic lineage and the level of
      expression in T cells is developmentally regulated. The CD4(-)8(-)44(+) early
      thymic immigrants and mature (CD4(+)8(-)/CD4(-)8(+)) thymocytes and T cells
      express low levels, whereas immature (CD4(-)8(-)44(-) and CD4(+)8(+)) thymocytes
      express high levels of LAR. Among bone marrow cells only uncommitted c
      kit(+)B220(+)CD19(-) precursors, but not B cell lineage committed c
      kit(+)B220(+)CD19(+) precursors, express low levels of LAR. In contrast to the c
      kit(+)B220(+)CD19(+) pre-BI cells from normal mice, counterparts of pre-BI cells
      from PAX-5-deficient mice express LAR, indicating that PAX-5-mediated commitment
      to the B cell lineage results in suppression of LAR. During differentiation of
      PAX-5-deficient pre-BI cell line into non-T cell lineages, expression of LAR is
      switched off, but it is up-regulated during differentiation into thymocytes.
      Thus, within the hemopoietic system, LAR appears to be a T cell lineage-specific
      receptor-type phosphatase. However, surprisingly, truncation of its phosphatase
      domains has no obvious effect on T cell development, repertoire selection or
      function.

PMID- 11241289
TI  - The transmembrane segment of invariant chain mediates binding to MHC class II
      molecules in a CLIP-independent manner.
AB  - Invariant chain (Ii) association with MHC class II molecules is strongly
      dependent upon interaction of CLIP (Ii exon 3, residues 81 - 104) with the
      peptide binding groove of the class II dimer. This dominant interaction does not
      adequately explain, however, the efficient association of Ii with class II
      molecules of diverse allelic and isotypic origin, which have markedly different
      affinities for synthetic peptides corresponding to CLIP. In agreement with other
      recent observations, we demonstrate here that class II molecules with occupied
      binding sites unable to engage CLIP maintain association with Ii in mild
      detergent. The association is direct and not mediated through unoccupied class II
      chains bound to properly assembled and loaded class II dimers, nor is it mediated
      through chaperones. The site of this CLIP-independent binding has been mapped
      using truncation mutants and an Ii-human transferrin receptor chimeric protein to
      the transmembrane segment of Ii. The existence of multiple low-affinity sites of
      interaction between MHC class II and Ii helps explain how effective occupancy of
      all newly synthesized class II molecules can occur despite substantial variations
      in the strength of CLIP-dependent association that arise from class II binding
      domain polymorphism. These data establishing a site of Ii-MHC class II
      association N-terminal to CLIP also provide new insight into the possible
      functional relationship between the sequential endocytic proteolysis of Ii from
      its C terminus and a series of contact sites with MHC class II molecules spread
      from the transmembrane region through to the tip of the lumenal segment of Ii.

PMID- 11241290
TI  - Intestinal parasitism terminates self tolerance and enhances neonatal induction
      of autoimmune disease and memory.
AB  - Genetic and environmental factors both influence autoimmune disease occurrence,
      but the identity and mechanism of action of environmental factors are poorly
      understood. Here we show that pinworm-infected neonatal but not adult mice,
      injected with an ovarian self peptide of the zona pellucida protein 3 (pZP3) in
      water and without adjuvant, develop Th2 responses and severe eosinophilic
      autoimmune ovarian disease. A strong Th2 memory response is recalled when, as
      adults, the mice are challenged with a regimen that elicits a strong Th1 response
      in naive adults. The strong Th2 autoimmune response included high levels of IL-4
      and IL-5 production by pZP3-specific T cells, and an IgG1-biased autoantibody
      response. The Th2 response ended promptly upon pinworm eradication, and partially
      resurfaced upon re-infection. We conclude that the rodent pinworm is an
      environmental agent that modifies the neonatal response to a self peptide,
      resulting in termination of the tolerance state and induction of a strong Th2
      associated autoimmune disease and T cell memory.

PMID- 11241291
TI  - Blockade of either alpha-4 or beta-7 integrins selectively inhibits intestinal
      mast cell hyperplasia and worm expulsion in response to Nippostrongylus
      brasiliensis infection.
AB  - Mast cells are known to express high levels of alpha4 integrins including
      alpha4beta7 and are found in increased numbers in mucosal inflammation. Mast cell
      accumulation is particularly prominent in the intestine following nematode
      infection. The adhesion molecule requirements for this process have not yet been
      defined. The role of alpha4 and beta7 integrin chains in the intestinal mast cell
      hyperplasia following infection of rats with the nematode parasite
      Nippostrongylus brasiliensis was examined in this study. Rats were infected with
      N. brasiliensis larvae and treated with either anti-alpha4 (TA-2), anti-beta7 or
      isotype-matched control antibodies. The initial mast cell hyperplasia in response
      to N. brasiliensis infection was significantly inhibited by either anti-alpha4 or
      anti-beta7 treatment. In contrast, the intestinal eosinophil response to N.
      brasiliensis infection was not reduced at day 14 or day 16. Elevations in serum
      IgE levels due to N. brasiliensis infection were also not inhibited by anti
      alpha4 or anti-beta7 antibody treatment. Anti-alpha4 antibody but not anti-beta7
      antibody treatment also induced a small but significant decrease in the numbers
      of mast cells in tongue tissue. These data suggest a role for alpha4 integrins,
      in particular alpha4beta7, in the regulation of mast cell precursor migration to
      the intestine.

PMID- 11241292
TI  - Purified MHC class I molecules inhibit activated NK cells in a cell-free system
      in vitro.
AB  - Natural killer cells have been shown to interact with MHC class I molecules via
      inhibitory receptors. However, it is not known whether the inhibition induced by
      MHC class I molecules requires other NK cell-target cell interactions. Thus, we
      examined whether purified MHC class I molecules alone were able to inhibit NK
      cell function. Purified H-2K(b) and H-2D(b) molecules inhibited the release of
      IFN-gamma from spleen (H-2(b))-derived lymphokine-activated killer (LAK) cell
      cultures stimulated by anti-NK1.1 antibody in a concentration-dependent manner.
      LAK cells generated from newborn mice that express low levels of MHC class I
      binding Ly49 inhibitory receptors were significantly less sensitive to inhibition
      by H-2K(b) compared to LAK cells from adult mice. Furthermore, LAK cells
      generated from spleen cells of Ly49C-transgenic mice were significantly more
      sensitive to inhibition by H-2K(b) compared to non-transgenic littermates. Taken
      together, the data indicate that MHC class I induced inhibition of NK cell
      mediated effector functions, as assessed by IFN-gamma release after NK1.1
      triggering, does not require additional cell surface molecules other than MHC
      class I.

PMID- 11241293
TI  - Silent infection of bone marrow-derived dendritic cells by Leishmania mexicana
      amastigotes.
AB  - Resolution of infection by Leishmania sp. is critically dependent on activation
      of CD4(+) T helper cells. Naive CD4(+) T helper cells are primed by dendritic
      cells which have responded to an activation signal in the periphery. However, the
      role of Leishmania-infected dendritic cells in the activation of an anti
      Leishmania immune response has not been comprehensively addressed. Using the
      highly controlled model system of bone marrow-derived dendritic cell infection by
      Leishmania mexicana cultured in vitro, we show that uptake of L. mexicana
      parasites does not result in activation of immature dendritic cells or secretion
      of IL-12. Incubation with L. mexicana promastigotes results in the activation of
      a small percentage of dendritic cells which do not appear to contain whole
      parasites. Activation of dendritic cells is not suppressed by infection, since
      infected cells can be fully activated on addition of activating stimuli.
      Therefore, uptake of intact Leishmania mexicana parasites is not sufficient to
      activate dendritic cells in vitro. We propose that these data provide a basis for
      interpreting the interactions between dendritic cells and all Leishmania sp.

PMID- 11241294
TI  - Lymphoid environment limits superantigen and antigen-induced T cell proliferation
      at high precursor frequency.
AB  - After superantigen challenge a significant proportion of superantigen-reactive T
      cells remain undivided. We provide evidence that the lymphoid environment limits
      T cell proliferation in the secondary lymphoid organs when the frequency of
      superantigen reactive T cells is unusually high. We monitored T cell
      proliferation and the percentage of undivided cells when the frequency of
      superantigen-reactive T cells was low (1%), intermediate (15%) or high (30-100%)
      by transferring fluorescently labeled cells into different recipients. When the
      frequency was low, practically all the reactive T cells entered cell cycle and
      proliferated maximally. At intermediate frequencies a large proportion of
      reactive T cells did not enter cell cycle and the whole population divided less.
      A further increase in reactive T cells did not alter the percentage of undivided
      cells but induced a further decrease in the number of cell divisions.
      Interestingly, the observations made with superantigens were confirmed with
      peptide antigen and TCR-transgenic mice. Moreover, in vivo and in vitro data
      suggest that dendritic cells are the most likely candidates in limiting T cell
      proliferation in the lymphoid environment. In conclusion, we show that the
      availability of APC in the lymphoid environment can quantitatively limit T cell
      priming.

PMID- 11241295
TI  - Virus-specific CD8(+) T cells with type 1 or type 2 cytokine profile are related
      to different disease activity in chronic hepatitis C virus infection.
AB  - The present study demonstrates that the quality of the virus-specific CD8(+) T
      cell responses, as detected by both enzyme-linked immunospot assay and specific
      MHC-peptide tetramers, changed in relation to the different disease activity in
      chronically hepatitis C virus-infected patients. Indeed, both the serum alanine
      transaminase and the hepatic flogosis levels were related directly to the
      frequencies of peripheral memory effector CD8(+) T cells producing IFN-gamma
      (Tc1), but inversely to the frequencies of those producing both IL-4 and IL-10
      (Tc2). Longitudinal studies highlighted that Tc1 or Tc2 responses fluctuate in
      relation to the different phases of the disease in the same individual.
      Furthermore, the Tc1 or Tc2 phenotype correlates with tetramer-positive cells
      expressing either CXCR3 or CCR3, promoting differential tissue localization of
      these cells and the maintenance of T cell homeostasis. Finally, studies at the
      level of liver-infiltrating lymphocytes indicated that they produced both IFN
      gamma and IL-4 with an evident bias towards the Tc1-like phenotype. Our studies
      suggest that the progressive fluctuation of Tc1 and Tc2 responses may play a
      fundamental role in maintaining a long-lasting low-level liver inflammation, and
      may constitute the basis for new therapeutic strategies of immune regulation.

PMID- 11241296
TI  - Reactivity pattern and cytokine profile of T cells primed by myelin peptides in
      multiple sclerosis and healthy individuals.
AB  - Autoreactive T cells specific for candidate myelin antigens, including myelin
      basic protein (MBP) and proteolipid protein (PLP), are thought to play an
      important role in the pathogenesis of multiple sclerosis (MS). Myelin-reactive T
      cells primed in vivo by myelin breakdown products or microbial cross-reactive
      antigens during the disease processes may exhibit a reactivity pattern and
      cytokine profile different from those in the normal T cell repertoire. In this
      study, we examined the precursor frequency, the reactivity pattern and cytokine
      profile of myelin-reactive T cells that were primed in vitro with overlapping
      peptides of MBP and PLP in patients with MS and healthy individuals. The results
      revealed that T cells specific for peptides of MBP and PLP occurred at a
      relatively higher precursor frequency in patients with MS than that in healthy
      individuals. We identified a number of dominant T cell epitopes within MBP and
      PLP, some of which were not previously detected using whole myelin antigens as
      the primary stimuli. Some residues represented common immunodominant regions that
      were detected in both MS patients and healthy controls while others were
      associated only with MS. MBP-reactive T cell lines generally exhibited a Th0-like
      cytokine profile. There was significantly increased Th1 cytokine production (i.
      e. TNF and IFN-gamma) among MS-derived T cell lines. PLP-reactive T cell lines
      had a distinct cytokine profile, producing predominantly TNF-alpha and little or
      not IFN-gamma and IL-4. The findings have important implications in the
      understanding of the role of myelin-reactive T cells in MS.

PMID- 11241297
TI  - IgA cross-reactivity between a nuclear autoantigen and wheat proteins suggests
      molecular mimicry as a possible pathomechanism in celiac disease.
AB  - Celiac disease patients display IgA antibody reactivity to wheat as well as to
      human proteins. We used serum IgA from celiac patients and, for control purposes,
      from patients with Crohn's disease, ulcerative colitis and from healthy
      individuals to identify celiac disease-specific IgA autoantigens in
      nitrocellulose-blotted extracts from various human cell types (epithelial,
      endothelial, intestinal cells, fibroblasts). The pattern, recognition intensity
      and time course of IgA autoreactivity was monitored using serial serum samples
      obtained from celiac children before and under gluten-free diet. By immunoblot
      inhibition and subcellular (cytosolic, nuclear) cell fractionation we identified
      a 55 kDa nuclear autoantigen expressed in intestinal, endothelial cells and in
      fibroblasts which was recognized by IgA antibodies of approximately half of the
      celiac disease patients and cross-reacted with wheat proteins. IgA reactivity to
      the 55 kDa autoantigen disappeared during gluten-free diet and was inhibited
      after pre-absorption of sera with wheat proteins but not with tissue
      transglutaminase, previously reported as the unique celiac disease-specific
      autoantigen. In conclusion, we defined a novel 55 kDa celiac disease-specific
      nuclear IgA autoantigen which shares epitopes with wheat proteins and which is
      different from tissue transglutaminase and calreticulin. Although the newly
      defined autoantigen was recognized much less frequently than tissue
      transglutaminase, our data suggest molecular mimicry between wheat and human
      proteins as a possible pathomechanism for the induction and/or maintenance of
      mucosal tissue damage in celiac disease.

PMID- 11241298
TI  - Mechanisms of expression of NADPH oxidase components in human cultured monocytes:
      role of cytokines and transcriptional regulators involved.
AB  - Human blood monocytes lose their capability to produce microbicidal oxidants
      during culture. We report that this process is associated with decreased
      gp91phox, p22phox and p47phox expression, release of PU.1 and CP-1 from gp91phox
      promoter, and PU.1 from p47phox promoter. However, in presence of IFN-gamma or
      TNF-alpha, the superoxide anion (O(2)(-)) production, the p47phox, gp91phox and
      p22phox expression, and the binding of PU.1 and CP-1 to DNA are maintained at the
      high levels observed in blood monocytes. To clarify the role of PU.1 in the
      expression of NADPH oxidase components, oligonucleotides competing for PU.1-DNA
      binding were added to cultured monocytes. These oligonucleotides abrogated the
      maintenance of gp91phox and p22phox expression by IFN-gamma and TNF-alpha, but
      did not inhibit the effect of these cytokines on p47phox expression and O(2)(-)
      production. Our results indicate that in monocytes the IFN-gamma- and TNF-alpha
      induced expression of gp91phox and p22phox, but not p47phox, requires the binding
      of PU.1 to gp91phox promoter. However, the preservation of O(2)(-) production by
      IFN-gamma and TNF-alpha is unrelated to their effect on gp91phox and p22phox
      expression.

PMID- 11241299
TI  - Delayed and deficient establishment of the long-term bone marrow plasma cell pool
      during early life.
AB  - Early life antibody responses are characterized by a rapid decline, such that
      antigen-specific IgG antibodies decline to baseline levels within months
      following infant immunization. This generic observation remains unexplained.
      Here, we have analyzed the induction and organ-localization of antigen-specific
      IgG antibody-secreting cells (ASC) following immunization of 1-week-old or adult
      BALB/c mice with tetanus toxoid (TT), a T-dependent antigen. Early life priming
      induced only slightly lower numbers of TT-specific IgG ASC in the spleen, and
      these reached adult levels following repeat immunization. In contrast, early life
      immunization generated much fewer bone marrow plasma cells than in adults, even
      after boosting. A similar limitation of the natural development of the bone
      marrow pool of ASC was observed. Transfer experiments with adult or early life
      spleen ASC indicated limited homing of TT-specific adult ASC to the bone marrow
      of 4-week-old mice as compared to adult recipients, whereas homing patterns were
      similar when early life or adult ASC were transferred into adult recipients.
      These observations suggest that a limited bone marrow B cell homing capacity and,
      as a result, relatively deficient bone marrow ASC responses, are critical factors
      which may explain the limited persistence of IgG antibodies to T-dependent
      antigens in early life.

PMID- 11241300
TI  - The generation of LMP2a-specific cytotoxic T lymphocytes for the treatment of
      patients with Epstein-Barr virus-positive Hodgkin disease.
AB  - Based upon the success of using polyclonal, Epstein-Barr virus (EBV)-specific CTL
      lines for the prophylaxis and treatment of patients with post-transplant
      lymphoproliferative disease (PTLPD), there is now considerable incentive to
      develop CTL directed against the sub-dominant EBV antigens EBNA1, LMP1 and LMP2,
      which are expressed by the tumor cells of Hodgkin disease and nasopharyngeal
      carcinoma. To develop a system for generating LMP2a-specific CTL in vitro, we
      transfected autologous immature dendritic cells (DC), which had been grown in the
      absence of serum, with LMP2a RNA in the presence of the cationic lipid DOTAP.
      This transfection method did not adversely affect the DC in terms of
      immunophenotyping and they expressed high levels of HLA class I and II and
      critical costimulatory molecules. These LMP2a(+) DC, as compared to DC which had
      been transfected with irrelevant RNA, were shown to be highly immunostimulatory
      in autologous mixed lymphocyte reactions and, importantly, could stimulate the
      generation of CD8(+) and CD4(+) CTL which exclusively recognized LMP2a-expressing
      targets. This specific cytotoxicity was confirmed using antibody blocking
      experiments and cytotoxicity assays of the separated T cell subsets. Using this
      DC-based system we could also reactivate LMP2a-specific memory in EBV
      seropositive donors whose polyclonal CTL response to LCL stimulation did not
      contain a LMP2a-specific component.

PMID- 11241301
TI  - Dendritic cell longevity and T cell persistence is controlled by CD154-CD40
      interactions.
AB  - Inflammatory mediators facilitate the maturation of dendritic cells (DC),
      enabling them to induce the activation, proliferation and differentiation of
      cognate T cells. The role of CD40 on DC and CD154 on T cells has been studied by
      the co-adoptive transfer of antigen-pulsed DC and TCR-transgenic (Tg) T cells in
      vivo. It is shown that in the absence of CD40-CD154 interactions, initial Tg T
      cell expansion occurs in vivo, but over time, T cell expansion cannot be
      sustained. The basis for the demise of the T cell population is likely due to the
      disappearance of the antigen-pulsed DC in the draining lymph nodes when CD154
      CD40 interactions are interrupted. These findings show that both T cell and DC
      persistence in vivo is dependent on CD40-CD154 interactions. In addition to the
      physical persistence of the DC, CD40 triggering of DC also greatly increases the
      period for which they can productively present antigen to Tg T cells. Hence DC
      persistence and antigen-presenting cell capacity are both dependent on CD40
      signaling. While TNF-alpha can mature DC as measured by a variety of criteria,
      the unique capacity of CD40 signaling to sustain T cell responses and induce DC
      maturation is underscored by the inability of TNF-alpha to rescue the immune
      deficiency of CD40(-/-) DC. Hence, the profound impact of CD154 deficiency on
      cell-mediated immunity may be due to its ability to limit the duration of antigen
      presentation in vivo and cause the premature demise of antigen-specific T cells.

PMID- 11241302
TI  - Epithelial and stromal syndecan-1 expression as predictor of outcome in patients
      with gastric cancer.
AB  - The prognostic value of the immunohistochemical expression of epithelial and
      stromal syndecan-1 was evaluated in 296 patients with gastric carcinoma. Formalin
      fixed, paraffin-embedded specimens of gastric adenocarcinomas were stained with
      mouse monoclonal antibody B-B4 against human syndecan-1. Loss of immunoreactivity
      (syndecan-1 immunoreactivity correlated with a higher stage of disease (stages II
      IV), tumour location in the upper third of the stomach, nodal metastases (N1 or
      N2), positive stromal syndecan-1 staining, deep tumour penetration (to subserosa
      or deeper = T2-T4), larger tumour size (> or = 5 cm) and intestinal type of
      cancer. No correlation between epithelial syndecan-1 immunoreactivity and age,
      gender, distant metastases, grade of differentiation or Borrmann classification
      was observed. Positive stromal syndecan-1 immunoreactivity correlated with
      decreased epithelial syndecan-1 expression, intestinal type of cancer and
      Borrmann type I. Patients with low epithelial syndecan-1 expression in cancer
      cells had worse overall survival than patients with strong epithelial syndecan-1
      staining (p = 0.0012). Stromal syndecan-1-positive patients had a worse outcome
      than patients with syndecan-1-negative stroma (p = 0.0193). In Cox multivariate
      analysis, stromal syndecan-1 immunoreactivity was a prognostic factor independent
      of TNM stage, surgery for cure and tumour size. Thus, the immunohistochemical
      expression of syndecan-1 might be a predictor of outcome in patients with gastric
      adenocarcinoma.

PMID- 11241303
TI  - Predictors for cutaneous basal- and squamous-cell carcinoma among actinically
      damaged adults.
AB  - Risk factors for non-melanoma skin cancer among populations with evidence of
      precursor damage are not well described. We examined and compared risk factors
      associated with the development of cutaneous basal-cell (BCC) or squamous-cell
      (SCC) carcinoma among a group of 918 adults with significant sun damage (> or =
      10 clinically assessable actinic keratoses) but no prior history of skin cancer.
      These adults were participants in a 5-year skin chemoprevention trial between
      1985 and 1992, who had been randomized to the placebo group and followed for
      occurrence of skin cancer. During the study, a total of 129 first SCC and 164
      first BCC lesions were diagnosed. The overall BCC and SCC incidence rates for
      this group of men and women, mean age 61 years, were 4,106 and 3,198 per 100,000
      person-years, respectively. Different constitutional and exposure factors were
      independently associated with BCC compared to SCC. Only increased age
      independently predicted BCC occurrence among this population. In contrast, older
      age along with male gender, natural red hair color and adult residence in Arizona
      for 10 or more years independently predicted SCC occurrence. The substantial
      incidence of skin cancer found among this population confirms the need for active
      dermatological monitoring among individuals with multiple visible actinic
      lesions.

PMID- 11241305
TI  - Tissue expression of human chorionic gonadotropin beta predicts outcome in
      colorectal cancer: a comparison with serum expression.
AB  - Production of the glycoprotein hormone human chorionic gonadotropin beta
      (hCGbeta) has been associated with more aggressive behavior in non-trophoblastic
      tumors. In this study, the prognostic value of immunohistochemical hCGbeta
      expression was evaluated in 239 patients with colorectal cancer. Paraffin
      embedded, formalin-fixed specimens were stained with hCGbeta-specific monoclonal
      antibody, and the results were compared with serum levels determined with an
      assay based on the same antibody. hCGbeta immunoreactivity was seen in 52 of 239
      tumors (22%). The difference in survival time between patients with
      histologically hCGbeta-negative (median survival 94 months) and -positive (median
      survival 27 months) tumors was statistically significant (p = 0.014). The risk
      ratio during follow-up for patients with positive hCGbeta tissue expression was
      1.65 (95% CI 1.11-2.46). In a Cox multivariate analysis, Dukes' stage, hCGbeta
      and age remained independent prognostic factors. There was moderate agreement
      between immunohistochemical and serum expression levels of hCGbeta (kappa =
      0.30). Using a combination of histological and serum levels of hCGbeta, the
      difference between survival rates was highly significant (p < 0.001). The
      accuracy when predicting 5-year survival status with the combined results of
      serum and tissue expression was 1.3% higher compared to hCGbeta tissue expression
      alone. Our results show that hCGbeta expression in both tumor tissue and serum
      has prognostic significance independent of other clinicopathological variables.
      Positive tumor staining does not always occur together with elevated serum
      levels, and the prognostic accuracy can slightly be increased by combining the
      results.

PMID- 11241304
TI  - Prognostic value of hyaluronan expression in non-small-cell lung cancer:
      Increased stromal expression indicates unfavorable outcome in patients with
      adenocarcinoma.
AB  - The prognostic value of hyaluronan (HA) was analyzed in a large number of
      patients (n = 261) with non-small-cell lung cancer (NSCLC) by staining archived
      tumor samples with a biotinylated HA-specific probe. The level of HA in the tumor
      cells and surrounding stroma was scored and compared with parallel CD44
      stainings, clinicopathological factors and survival data. Adenocarcinomas were
      characterized by a low percentage of HA-positive cells with low staining
      intensity compared with squamous-cell and large-cell/anaplastic carcinomas. The
      HA signal in the peri-tumoral stroma was often higher than that in the uninvolved
      stroma in all subgroups of NSCLC. CD44 and HA associated with the cancer cells
      showed a strong positive correlation with each other. In the whole tumor
      material, dominated by squamous-cell carcinomas (n = 168), recurrences were more
      often found in cases showing a low percentage of cancer cell-associated HA.
      However, within the adenocarcinoma subgroup (n = 68), a high percentage of cell
      associated HA was correlated with poor tumor differentiation. Also specific for
      the adenocarcinoma subgroup was the increased number of recurrences in cases with
      a strong stromal HA signal. In survival analysis of the whole material (n = 189),
      a low percentage of HA-positive cancer cells was associated with a shortened
      disease-free survival (DFS) together with stage and tumor type. However, in the
      subgroup of patients with adenocarcinoma (n = 49), a strong stromal signal for HA
      predicted poor DFS. The level of HA in the stroma of adenocarcinomas retained its
      prognostic value in Cox's multivariate analysis. These results indicate that the
      frequency and intensity of HA has a significant prognostic value in NSCLC,
      particularly when the histological subtypes are analyzed as separate entities.

PMID- 11241307
TI  - Lymphatic microvessel density as a novel prognostic factor in early-stage
      invasive cervical cancer.
AB  - Few data on the influence of lymphatic microvessel density (MVD) on survival in
      cancer are available since until recently there was no reliable
      immunohistological marker for lymphatic endothelium. Using an antibody staining
      podoplanin, a novel marker for lymphatic endothelium, lymphatic MVD in tissue
      samples of 85 patients with cervical cancer classification pT1b treated by
      radical hysterectomy was investigated. Survival was determined using univariate
      and multivariate analyses. Lymphatic MVD was also compared to MVD assessed by
      immunostaining against factor VIII-related antigen, which is considered a marker
      for blood vessels. Patients with >5 lymphatic microvessels/0.25 mm(2) field had
      significantly better overall survival (mean 91.8 months) than those with < or =5
      lymphatic microvessels/field in univariate analysis (mean 113 months) (p =
      0.0105, log-rank test). In multivariate analysis, lymphatic node involvement (p
      =0.0183), vessel infiltration (p =0.0158) and lymphatic MVD (p =0.0269) remained
      independent prognostic factors. No correlation between lymphatic MVD and various
      clinical and histopathological parameters was observed. Correlation between
      lymphatic MVD and MVD assessed by immunostaining against factor VIII was only
      weak (p = 0.004, r = 0.312, Spearman's coefficient of correlation). Our results
      suggest that increased lymphatic MVD is associated with favorable prognosis in
      early-stage cervical cancer.

PMID- 11241308
TI  - Loss of p16(INK4a) expression correlates with decreased survival in pediatric
      osteosarcomas.
AB  - Abnormalities of the G1 cell-cycle checkpoint are commonly reported in cancers at
      various anatomic sites. pRB, p16(INK4a) and cyclin D1 are critical G1-checkpoint
      proteins responsible for maintaining the balance of cellular proliferation. We
      examined a series of 38 pediatric osteosarcomas for abnormal expression of pRB,
      p16(INK4a) and cyclin D1 by immunohistochemical analysis of archival biopsy
      specimens. Overall, 17/38 (45%) osteosarcomas showed evidence of G1-checkpoint
      abrogation, including 11/38 (29%) with loss of pRB expression and 6/38 (16%) with
      loss of p16(INK4a) expression. Cyclin D1 over-expression was not detected. There
      was an inverse correlation between loss of pRB and p16(INK4a) expression (p =
      0.07). pRB and p16(INK4a) abnormalities were independent of site of disease,
      presence of metastasis at diagnosis and percentage of tumor necrosis in the
      resection specimen. Clinical follow-up was available on all patients (median 31.6
      months, range 5.9-116 months). Absence of p16(INK4a) expression significantly
      correlated with decreased survival in univariate analysis (p = 0.03), while loss
      of pRB expression did not affect survival. Immunohistochemical analysis of
      p16(INK4a) expression in pediatric osteosarcomas may be a useful adjunctive
      marker of prognosis.

PMID- 11241306
TI  - TAP1 down-regulation in primary melanoma lesions: an independent marker of poor
      prognosis.
AB  - Melanoma tumor thickness is a major prognostic factor. Thin lesions, however, may
      metastasize, and sometimes thick tumors may not. To investigate the role of HLA
      class I-mediated antigen presentation, we correlated the expression of components
      of the antigen-processing machinery in primary melanoma lesions with their
      thickness and with the development of metastases. Seventeen formalin-fixed,
      paraffin-embedded primary melanomas thinner than 0.76 mm and 21 thicker than 1.50
      mm were stained with anti-LMP2, -LMP7, -TAP1, -TAP2, -HLA class I and -beta2
      microglobulin monoclonal antibodies. Twenty patients remained tumor-free in the
      follow-up period (10.5 +/- 1.8 years). Eighteen patients relapsed within a median
      period of 15.0 months following tumor excision. Expression of all markers in the
      tested lesions was down-regulated, the frequency ranging from about 40% for LMP
      and TAP subunits to about 70% for HLA class I antigens. Expression of all markers
      was not correlated with tumor thickness. Only TAP1 and TAP2 down-regulation was
      significantly (p = 0.026 and 0.042, respectively) correlated with the development
      of metastases. This correlation was independent of tumor thickness for TAP1. We
      suggest that TAP1 and probably TAP2 expression in primary lesions represents an
      independent prognostic marker in melanoma. Abnormalities in antigen presentation
      may account for the lack of absolute correlation between tumor thickness and
      prognosis.

PMID- 11241309
TI  - Relative levels of SCCA2 and SCCA1 mRNA in primary tumors predicts recurrent
      disease in squamous cell cancer of the head and neck.
AB  - Squamous cell carcinoma antigen (SCCA) is widely used as a serum marker in
      cancers of the uterine cervix, the head and neck, lung and esophagus. Two
      isoforms of SCCA, deriving from 2 highly homologous serine proteinase inhibitor
      genes, are co-expressed in normal and malignant squamous epithelium, but it is
      mainly the acidic isoform SCCA2 that is present in the circulation of cancer
      patients. We studied the relative levels of SCCA2 and SCCA1 mRNA in frozen
      sections of squamous cell carcinomas of the head and neck (SCCHN) in relation to
      disease recurrence, using a new reverse transcription-polymerase chain reaction
      based technique for accurate quantitation of relative mRNA levels. Primary tumors
      from 30 SCCHN patients, recurrent tumors from 11 patients and normal epithelium
      from 16 controls were examined. In patients responding to initial therapy (n =
      26), an elevated SCCA2/SCCA1 mRNA ratio in the primary tumor predicted recurrence
      independent of clinical stage (p = 0.011). The relative risk of developing a
      recurrence was 7.2 (CI 1.2-13.3) in patients with elevated vs. normal SCCA2/SCCA1
      mRNA ratios. We demonstrate that subtle differences in expression levels of the
      SCCA genes are reflected in the course of the SCCHN disease and may provide a
      target for molecular grading of SCCHN tumors. If this finding can be confirmed in
      a larger study the SCCA2/SCCA1 mRNA ratio in primary tumors could be useful for
      individual selection of treatment strategy for patients with head and neck
      cancer.

PMID- 11241310
TI  - Expression of tissue inhibitor of matrix metalloproteinase-2 correlates with
      activation of matrix metalloproteinase-2 and predicts poor prognosis in tongue
      squamous cell carcinoma.
AB  - Matrix metalloproteinase 2 (MMP-2) plays a crucial role in invasion and
      metastasis of malignant tumors. Membrane type 1-MMP (MT1-MMP) was originally
      identified as an activator of MMP-2. Tissue inhibitor of MMP-2 (TIMP-2) was
      identified as an inhibitor of MMP-2 and MT1-MMP. However, TIMP-2 was reported to
      be essential for cell-mediated activation of MMP-2 and thus, the contribution of
      TIMP-2 to tumor invasion has remained controversial. This study was designed to
      analyze the role of TIMP-2 for activation of MMP-2 and its prognostic value in
      tongue squamous cell carcinoma (SCC). Expression of MMP-2, MT1-MMP and TIMP-2
      protein was analyzed by immunohistochemistry, and their association with clinical
      factors was evaluated in 51 patients treated surgically for tongue SCC.
      Expression of MMP-2, MT1-MMP and TIMP-2 was significantly correlated with local
      and distant metastatic tumor recurrence and poor prognosis (MMP-2 and MT1-MMP, p
      < 0.0001; TIMP-2, p = 0.0002). Activation of MMP-2, analyzed by gelatin
      zymography in 17 fresh specimens, was remarkably associated with expression of
      MMP-2 (r = 0.779, p < 0.0001), MT1-MMP (r = 0.674, p < 0.0022) and TIMP-2 (r =
      0.858, p < 0.0001). Increased expression of TIMP-2, as well as MMP-2 and MT1-MMP,
      was an important prognostic factor in patients with tongue SCC.

PMID- 11241311
TI  - Expression of cathepsins B and S in the progression of prostate carcinoma.
AB  - Cathepsins B and S (CatB, CatS) are lysosomal cysteine proteases which, among
      other functions, appear to play a role in cancer progression in different tumor
      models due to their matrix-degrading properties. To investigate their possible
      involvement in the development of prostate carcinoma, we immunohistochemically
      analyzed CatB and CatS in 38 primary human prostatic adenocarcinomas, as well as
      concomitant high-grade prostatic intra-epithelial neoplasia, nodular hyperplasia
      and normal tissue. CatB expression was observed in 28 (74%) and CatS in 32 (84%)
      carcinomas, being concomitant in 24 cases (63%). High-grade intra-epithelial
      neoplasia expressed CatB in 20/23 cases (87%), and a similar result was obtained
      for CatS, with expression of both coinciding in 18 cases (78%). In non-neoplastic
      tissue, strong expression of both proteases was observed in macrophages, inflamed
      glands and transitional metaplasia, whereas atrophic glands and basal cells of
      normal glands displayed intense CatB positivity. We conclude that CatB and CatS
      are often expressed together in neoplastic prostatic cells from pre-invasive to
      invasive and clinically detectable stages, suggesting a putative role in local
      invasion, though other functions cannot be ruled out.

PMID- 11241312
TI  - DNA-synthesizing enzymes in breast cancer (thymidine kinase, thymidylate synthase
      and thymidylate kinase): association with flow cytometric S-phase fraction and
      relative prognostic importance in node-negative premenopausal patients.
AB  - S-phase fraction (SPF) is a reference for cell-kinetic analysis. In this study,
      the links between SPF and the essential enzymes participating in the pyrimidine
      synthesis were investigated in breast cancer and their relationships with the
      natural history of the disease were compared. We measured thymidine kinase (TK)
      for salvage synthesis, thymidylate synthase (TS) for de novo synthesis and
      thymidylate kinase (TMK), which is required for both pathways. Our study
      population consisted of 211 premenopausal women with node-negative tumors. SPF
      was assessed prospectively by flow cytometry, whereas enzyme activities were
      measured retrospectively in cytosols using radioenzymatic methods. Among the
      enzymes analyzed, only TK demonstrated a strong correlation with SPF (r(s) =
      0.59). In univariate analysis, high SPF and high levels of TK were associated
      with increased risk of developing distant recurrences (p < 0.001). Correlations
      with other prognostic factors (histological grade, steroid receptors, DNA ploidy
      status, urokinase plasminogen activator and plasminogen activator inhibitor type
      1) confirmed a parallel association of SPF and TK with the most aggressive
      tumors. In contrast, TS and TMK were not associated with prognosis. After
      adjustment for SPF, the risk of relapse increased significantly with TK values.
      Subgroup analysis showed that additional information was provided by TK in the
      tumors with low SPF. When urokinase plasminogen activator (uPA) was a candidate
      variable in multivariate analysis, TK remained significant. Combined with SPF and
      uPA, TK could be useful to define premenopausal node-negative patients with
      rapidly proliferating tumors at a high risk of metastatic disease.

PMID- 11241313
TI  - Prognostic value of codon 918 (ATG-->ACG) RET proto-oncogene mutations in
      sporadic medullary thyroid carcinoma.
AB  - We have determined the frequency of 918 RET proto-oncogene mutations (ATG-->ACG)
      in primary MTC tumors and metastases and correlated the presence or absence of
      this mutation with the clinical outcome of patients suffering from sporadic
      medullary thyroid carcinoma (MTC). A total of 197 samples, consisting of both
      primary tumors and lymph node metastases from 34 patients with sporadic MTC, were
      collected for PCR analysis of the RET 918 mutation. In 75 of the samples (38%),
      codon 918 (ATG-->ACG) mutations could be detected. The mutations showed a
      heterogeneous distribution: 21/34 patients (62%) had mutations in at least 1
      tumor sample, and in 13 patients (38%) the mutation was present in all examined
      samples. Patients were considered 918mt when at least 1 tumor sample showed the
      RET 918 mutation. These 918mt and 918 wild-type (918wt) patients did not differ
      significantly concerning sex, age at diagnosis, TNM stage at diagnosis, number of
      examined tumor samples or follow-up time. However, 918mt patients showed more
      aggressive development of distant metastases during follow-up (p = 0.032,
      Fisher's exact test) with decreased metastases-free survival (p < 0.005, log-rank
      test). Furthermore, 918mt patients had a significantly lower survival rate than
      918wt patients (p = 0.048, log-rank test). These data show that the RET codon 918
      mutation has a prognostic impact on patients with sporadic MTC which may
      influence follow-up treatment.

PMID- 11241314
TI  - Stromal expression of fibroblast activation protein/seprase, a cell membrane
      serine proteinase and gelatinase, is associated with longer survival in patients
      with invasive ductal carcinoma of breast.
AB  - Fibroblast activation protein (FAP)/seprase is a serine integral membrane
      proteinase with gelatinase activity, which is expressed by activated fibroblasts
      in the stroma of various epithelial cancers, mesenchymal tumors and breast-cancer
      cells, as well as during wound repair. However, the pathophysiologic significance
      of its expression remains poorly understood. The present study was designed to
      reveal the impact of stromal expression of FAP/seprase on survival in human
      breast cancer. Immunohistochemical expression of FAP/seprase was restricted to
      stromal fibroblasts adjacent to tumor-cell nests but not cancer cells, which was
      confirmed by double-labeling immunohistochemistry. Clinicopathologic analysis
      revealed that more abundant FAP/seprase expression in 112 cases of invasive
      ductal carcinoma is associated with longer overall and disease-free survival.
      Multivariate analysis with other clinicopathologic factors demonstrated that
      FAP/seprase expression is an independent prognostic factor. The effect on the
      survival rate of FAP/seprase was also apparent in cases with lymph node
      metastasis. FAP/seprase expression is one of the manifestations of the stromal
      reaction (i.e., matrix turnover); thus, invasive ductal carcinomas with fewer
      stromal reactions expressing FAP/seprase may be more aggressive.

PMID- 11241315
TI  - Expression of Melan-A/MART-1 antigen as a prognostic factor in primary cutaneous
      melanoma.
AB  - In this study we assessed the expression of the Melan-A/MART-1 antigen by
      immunohistochemistry using monoclonal antibody A103 in 73 primary cutaneous
      melanomas and its correlation with tumor staging and patient survival. Melan
      A/MART-1 was expressed in 90% of primary tumors, with loss of expression
      increasing with Breslow thickness. Kaplan-Meier analysis demonstrated a
      significantly reduced disease-free interval and overall survival rate for
      patients not expressing this antigen. The poor prognosis of such patients was
      even worse for those presenting with a primary melanoma and a Breslow thickness
      of > or = 1 mm. Thus, Melan-A/MART-1 is not only a useful and specific additional
      marker for the diagnosis of primary cutaneous melanoma, but it may also help
      refine the prognosis of patients with malignant melanoma.

PMID- 11241316
TI  - Helix pomatia agglutinin lectin-binding oligosaccharides of aggressive breast
      cancer.
AB  - Predicting long-term outcome after breast-cancer diagnosis remains problematic,
      particularly for patients with clinically small, axillary lymph node- negative
      tumours. Evidence suggests that the lectin Helix pomatia agglutinin (HPA)
      identifies oligosaccharides associated with poor-prognosis cancer. Our aim was to
      identify oligosaccharides that bind HPA in aggressive breast cancers. Breast
      cancer cell lines (MCF-7, BT-549 and BT-20) and a cell line from human milk (HBL
      100), which showed a range of HPA-binding intensities, were used to extract HPA
      binding glycoproteins. Oligosaccharides were released using anhydrous hydrazine
      and separated on a range of HPLC matrices. We investigated whether HPA-binding
      oligosaccharides from cell lines were present in human breast-cancer tissues,
      using 69 breast-cancer specimens from patients with between 5 and 10 years'
      follow-up. A monosialylated oligosaccharide was over-expressed in the cell line
      that bound HPA strongly. Further analysis by normal-phase HPLC showed that the 2
      aminobenzamide-conjugated oligosaccharide had a hydrodynamic volume of 4.58
      glucose units (HPAgly1). Increased expression of HPAgly1 was associated with HPA
      staining of breast-cancer specimens (Student's t-test p = 0.025). Analysis of
      oligosaccharide levels and disease-free survival after treatment for breast
      cancer indicated a shorter disease-free interval for patients with elevated
      levels of HPAgly1. This is the first time that histochemical lectin staining has
      been correlated with biochemical mapping of oligosaccharides. Using this
      approach, we have identified a monosialylated HPA lectin-binding oligosaccharide
      present in breast-cancer cells grown in vitro which is elevated in breast-cancer
      specimens that bind the lectin.

PMID- 11241317
TI  - Altered DNA repair capacity and bleomycin sensitivity as risk markers for non
      small cell lung cancer.
AB  - DNA repair capacity in human peripheral blood lymphocytes was monitored by the
      repair rate of bleomycin-induced DNA damage using an alkaline single-cell gel
      electrophoresis assay (comet assay). DNA repair capacity, after 15 min repair
      time, in lymphocytes of non-small cell lung cancer patients (n = 160) and
      controls (n = 180) was 67% and 79.3%, respectively (p < 0.0004). Bleomycin
      sensitivity defined as the tail moment of bleomycin-treated peripheral blood
      lymphocytes, without allowing time for DNA repair, was significantly higher in
      lung cancer patients than in tumor-free hospital controls (p < 0.0001). There was
      no correlation, in either patient or control group, between the bleomycin
      sensitivity and DNA repair capacity with age or gender. The median values of DNA
      repair capacity and sensitivity in controls were used as the cut-off points for
      calculating odds ratios (OR). After adjustment for age, gender and smoking
      status, the cases vs. controls had reduced DNA repair capacity (OR = 2.1; 95%
      confidence limit [CL] 1.1-4.0) and increased bleomycin sensitivity (OR = 4; 95%
      CL 2.2-7.4). For current smokers, the adjusted risk associated with bleomycin
      sensitivity was 2.3 (95% CL 1.1-4.9). We conclude that our standard comet assay
      as a phenotypical repair test has sufficient sensitivity and rapidity allowing
      application to both native and cryopreserved lymphocytes. Bleomycin sensitivity
      and DNA repair capacity were found to be 2 independent susceptibility markers for
      non-small cell lung cancer, confirming similar investigations with different
      marker end points. The latter were much more time consuming than the method used
      in our study. Thus, the comet assay is more suitable for screening large numbers
      of individuals in epidemiological studies. Validation of this assay in large
      prospective studies for the identification of subjects at high risk for non-small
      cell lung cancer is now warranted.

PMID- 11241318
TI  - Expression of survivin in esophageal cancer: correlation with the prognosis and
      response to chemotherapy.
AB  - Survivin, a new member of the inhibitor-of-apoptosis (IAP) family, has been
      reported to be expressed in many cancers but not in differentiated normal tissue.
      Its expression in esophageal cancer, however, has not been reported. We
      investigated 51 esophageal cancers and their adjacent normal epithelial tissues
      for mRNA expression of survivin by RT-PCR. The survivin expression in esophageal
      cancer tissue was significantly higher than that in normal esophageal tissue
      (0.211 +/- 0.226 vs. 0.057 +/- 0.135, p < 0.0001). pN4 tumors had significantly
      higher survivin expression than the pN0-3 tumors (p = 0.0093). Fourteen patients
      with advanced esophageal cancer had received chemotherapy prior to surgery. The
      survivin expression in the cancer tissue in patients who achieved a partial
      response (PR) was significantly lower than that in patients with no change (NC)
      and in patients with progressive disease (PD; 0.099 +/- 0.134 vs. 0.320 +/-
      0.222, p = 0.0434). The median survival for patients with high survivin
      expression (9.0 months) was less than that for patients with low survivin group
      expression (30.0 months, p = 0.0023). Survivin expression was one of the
      significant predictors of survival on univariate analysis (hazard ratio 2.471;
      95% confidence interval 1.104-5.533). The results suggest that survivin
      expression may provide prognostic information in patients with esophageal cancer.

PMID- 11241319
TI  - Frequency of CYP2A6 gene deletion and its relation to risk of lung and esophageal
      cancer in the Chinese population.
AB  - Cytochrome P450 2A6 (CYP2A6) plays an important role in the oxidation of nicotine
      and in the activation of tobacco-related carcinogens, such as N
      nitrosodimethylamine, N-nitrosodiethylamine and 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone. It has been suggested that individuals with defective CYP2A6
      alleles are at a lower risk of becoming smokers and of developing lung and other
      tobacco-related cancers. We examined the relationship between the CYP2A6 gene
      deletion and susceptibility to lung and esophageal cancer in a Chinese population
      via a hospital-based case-control study. The CYP2A6 gene deletion was determined
      by a PCR-based approach in 326 healthy controls, 149 patients with esophageal
      squamous-cell carcinoma and 151 patients with lung cancer. The allele frequency
      of the CYP2A6*4 deletion was 8.6% among controls compared with 8.4% among cases
      with esophageal squamous-cell carcinoma (p = 0.29) or 13.2% among cases with lung
      cancer (p < 0.01). Individuals who harbored at least one CYP2A6*4 deletion allele
      were at a 2-fold increased risk of developing lung cancer (95% confidence
      interval [CI] = 1.2-3.2) compared with those without a defective CYP2A6 allele.
      This effect was mainly limited to squamous-cell carcinoma and to non-smokers,
      although a joint effect of CYP2A6 deletion and tobacco smoking on lung cancer
      risk was observed among heavy smokers. The overall risk of esophageal cancer did
      not appear to be associated with this CYP2A6 genetic polymorphism (odds ratio
      [OR] = 1.2, 95% CI = 0.7-2.1). However, stratified analysis suggested an excess
      risk with borderline significance (OR = 2.1; 95% CI = 1.0-4.5) related to the
      CYP2A6*4 allele among non-smokers. The distribution of CYP2A6 genotype frequency
      was not significantly different (p = 0.40) between smokers (n = 174) and non
      smokers (n = 152) in this study population. Our results demonstrate that the
      CYP2A6 gene deletion is associated with an increased risk of lung and esophageal
      cancer but not with a reduced tendency to smoke.

PMID- 11241320
TI  - Genotype and phenotype factors as determinants of desmoid tumors in patients with
      familial adenomatous polyposis.
AB  - Desmoids represent the most important cause of death, after colorectal cancer, in
      patients affected with familial adenomatous polyposis (FAP), an inherited disease
      due to mutations in the APC gene. The aims of our study were to estimate the risk
      of developing desmoids in FAP patients and to evaluate the association between
      desmoids and different risk factors. The occurrence of desmoids, colorectal
      cancer and other extra-colonic manifestations were assessed in 897 FAP patients,
      653 of whom were also investigated for APC mutations. Odds ratios (OR) and
      corresponding 95% confidence intervals (CI) were computed using an unconditional
      multiple logistic regression model. Desmoids developed in 107 patients (11.9%),
      with a cumulative risk of 20.6%. Females had a significantly higher risk than
      males (OR = 2.1; 95% CI 1.4-3.1). Family history of desmoids (OR = 8.75; 95% CI
      5.66-13.51), osteomas (OR = 2.9; 95% CI 1.8-4.8) and epidermoid cysts (OR = 1.8;
      95% CI 1.1-3.2) was also significantly associated with the occurrence of disease.
      Subjects with APC mutations beyond codon 1444 had a 12-fold increased risk,
      compared with patients with mutations located upstream. Mutations beyond codon
      1309 conferred a 17-fold higher risk, compared with mutations upstream codon 452.
      Multivariate analysis identified as independent predictors mutation beyond codon
      1444 (OR = 6.2; 95% CI 2.5-15.8), family history of desmoids (OR = 5.8; 95% CI
      3.1-10.6), female gender (OR = 2.1; 95% CI 1.1-3.8) and the presence of osteomas
      (OR = 1.9; 95% CI 1.1-3.4). Our results indicate that integrating genetic and
      clinical data is helpful in defining subgroups of patients at higher risk for
      desmoids, who may benefit from specific prevention programs.

PMID- 11241321
TI  - Altered expression and mutation of beta-catenin gene in gastric carcinomas and
      cell lines.
AB  - beta-catenin serves not only as a structural component of the E-cadherin-mediated
      cell-cell adhesion system, but also as a signaling molecule of the Wnt/wingless
      pathway. Deregulated expression of beta-catenin and mutations of the gene have
      been identified in a number of human malignancies. To determine the role of beta
      catenin defects in stomach cancer, we investigated beta-catenin exon 3 mutations
      and altered protein expression in 77 primary gastric carcinomas and 11 cell
      lines. In addition, the immunohistochemical expression pattern of beta-catenin in
      303 consecutive gastric cancers was determined and their relationships with
      clinicopathologic features and patient outcome were investigated. This study
      revealed 5% (4 of 77) tumors and 27% (3 of 11) cell lines with beta-catenin gene
      alteration, 6 missense mutations, and 1 interstitial deletion. These genetic
      changes were shown to correlate closely with nuclear localization of the protein
      (p = 0.001). In an immunohistochemical analysis, abnormal expressions of beta
      catenin, such as nuclear accumulation and loss of membranous distribution, were
      detected in 27% (81 of 303) of tumors overall. These altered beta-catenin
      expressions were more commonly observed in 37% (58 of 158) diffuse type gastric
      carcinomas (p < 0.001). Loss of membranous beta-catenin staining was associated
      with poor survival (p = 0.045). In conclusion, our results demonstrate that beta
      catenin mutations are common in gastric cancer cell lines but occur infrequently
      in gastric carcinoma tissues. These mutations are one of the causes of the
      nuclear accumulation of beta-catenin. Frequent abnormalities of beta-catenin
      expression in gastric carcinoma support the idea that both structural and
      signaling functions of the protein play a critical role in gastric
      carcinogenesis.

PMID- 11241322
TI  - Nucleosomes in serum of patients with benign and malignant diseases.
AB  - High quantities of mono- and oligonucleosomes circulate in the blood of patients
      with malignant tumors. For their direct quantification in serum, we modified the
      Cell Death Detection(plus)-ELISA for its application in liquid materials. We
      examined sera samples from 590 persons, including 418 patients with malignant
      tumors, 109 patients with benign diseases and 63 healthy persons. We also
      observed the kinetics of the concentration of nucleosomes in serum samples from
      20 patients undergoing chemotherapy and from 16 patients undergoing radiotherapy.
      Sera of patients with malignant tumors contained considerably higher
      concentrations of nucleosomes (mean = 350 arbitrary units [AU], median = 190 AU)
      compared with those of healthy persons (mean = 36 AU, median = 24 AU; p = 0.0001)
      and patients with benign diseases (mean = 264 AU, median = 146 AU; p = 0.072).
      Concerning the follow-up investigations, the concentration of nucleosomes in
      serum increased 24-72 hr after the first application of chemotherapy and 6-24 hr
      after the start of radiotherapy. A subsequent decrease was often correlated with
      regression of the tumor. In patients undergoing chemotherapy, an increase in the
      baseline values of circulating nucleosomes >50%, which were determined before
      each new therapeutic cycle, was correlated with progression of disease; all
      patients with disease regression showed a decrease >50% of the baseline values.
      In patients undergoing radiotherapy, an early decrease of the nucleosomal
      concentration (< or = 1 day after the initial peak during therapy) to low minimum
      levels (< or = 100 AU) correlated with good clinical outcome; a late decrease (>1
      day) to higher minimum levels (>100 AU) was associated with a worse clinical
      outcome. Thus, the concentration of nucleosomes in serum might be a useful tool
      for monitoring the biochemical response during antitumor therapy, especially for
      the early estimation of therapeutic efficacy.

PMID- 11241323
TI  - Metallothionein expression in ovarian cancer in relation to histopathological
      parameters and molecular markers of prognosis.
AB  - Metallothioneins (MTs) and glutathione constitute the major fractions of
      intracellular thiol factors. Abundant nucleophilic sulfhydryl groups can interact
      with many electrophilic substances, including several anti-neoplastic agents,
      participate in controlling intracellular redox potential, and act as scavengers
      of reactive oxygen species. In the present study, we examined the relation of MTs
      (alone and in combination with glutathione) to histopathological parameters and
      survival time of ovarian cancer patients. Expression of the major MT isoforms (MT
      1 and MT-2) was determined by immunohistochemistry on paraffin-embedded tumor
      specimens from 189 patients, 151 suffering from primary epithelial ovarian cancer
      and 38 from recurrences. MT was negatively associated with survival time when all
      patients with primary carcinomas (n = 151) were analyzed (p = 0.049, log-rank
      test). However, no significant association between MT expression and survival was
      obtained when subgroups of patients with histological grade 1, 2 or 3 carcinomas
      were analyzed. Similarly, no significant association of MT expression and
      survival was obtained with the proportional hazards model adjusted for
      histological grade. This scenario can be explained by a correlation between MT
      expression and histological grade: MT was detectable in 26%, 48% and 62% of grade
      1, 2 and 3 carcinomas, respectively (p = 0.008, chi(2) test). An interesting
      hypothesis is generated by combined analysis of MT and total glutathione content
      (GSH). The product of MT and GSH levels (MT x GSH) was negatively associated with
      survival of grade 1 carcinomas (p = 0.021, log-rank test) but not with grade 2
      and 3 carcinomas (p = 0.176 and 0.403, respectively). When MT x GSH was greater
      than the median, 25% of patients with grade 1 carcinomas died within 235 days. In
      contrast, all patients with grade 1 carcinomas survived when MT x GSH in tumor
      tissue was smaller than the median. This suggests that high expression of
      sulfhydryl factors might facilitate survival and progression of low-grade ovarian
      cancer cells. A significant correlation was obtained between MT expression and
      mutant p53 (p = 0.037, chi(2) test). However, this might be an indirect effect
      since both MT (p = 0.008) and mutant p53 (p = 0.000) were associated with
      histological grade. In conclusion, MT expression as well as the product of MT and
      GSH were associated with histological grade of primary ovarian carcinomas. High
      expression of both sulfhydryl factors may identify a subgroup of low-grade
      carcinomas with an increased risk of progression.

PMID- 11241324
TI  - Quantitative p21(waf-1)/p53 immunohistochemical analysis defines groups of
      primary invasive breast carcinomas with different prognostic indicators.
AB  - We used image cytometry to quantify the immunohistochemical expression of p21(waf
      1) and p53 in primary breast carcinoma. Ratio analysis of the quantified
      p53/p21(waf-1) protein expression allowed us to define 3 groups of carcinomas,
      each characterized by specific pathological and biological profiles. The negative
      (NEG) group, characterized by negligible expression of both proteins, comprised
      small-sized, low-grade tumors associated with high contents of hormonal receptors
      and low growth fraction. In the NEG group, Ki-67 labelling index area (%LIa) was
      the only significant prognostic indicator. The P53H group, characterized by
      prevalence of p53 %LIa, was constituted by large-sized, high-grade tumors showing
      low hormonal receptor contents and high growth fraction. In the P53H group, both
      p53 and Ki-67 were inversely associated with both estrogen receptor (ER) and
      progesterone receptor (PGR), suggesting that extensive p53 immunostaining is
      related to poor differentiation and high proliferation. Only N status was
      prognostically significant in the P53H group. The P21H group, characterized by
      prevalence of p21(waf-1) %LIa, displayed intermediate pathological and biological
      features. A significant association between p53 and p21(waf-1) expression
      suggested functional stabilization of wtp53 and therefore possible DNA damage
      dependent G1/S arrest (genetic instability) in the P21H group; P21(waf
      1)expression was significantly associated with the presence of node metastasis.
      Patients in the P21H group had a higher recurrence rate and a shorter disease
      free time interval from surgery with respect to the NEG group. Proportional
      hazard regression analysis disclosed Ki-67 %LIa and, to a lesser degree, PGR %LIa
      as significant relapse-free survival prognostic indicators.

PMID- 11241325
TI  - UFT plus oral leucovorin calcium (Orzel) and radiation in combined modality
      therapy: a comprehensive review.
AB  - 5-fluorouracil (5-FU) has become the most commonly used drug in combination with
      radiation therapy. The recent availability of oral formulations of 5-FU in
      conjunction with the ability to modulate the anabolic and catabolic metabolism of
      5-FU with leucovorin and dihydropyrimidine dehydrogenase (DPD) inhibitors,
      respectively, may provide a substantial improvement in the ease of administration
      and the efficacy of fluoropyrimidine therapy. Several oral fluoropyrimidines are
      under investigation. UFT (uracil:tegafur) plus oral leucovorin (Orzel) is the
      first oral DPD-inhibitory fluoropyrimidine. With daily administration, Orzel
      achieves similar concentrations of 5-FU obtained with continuous-infusion 5-FU.
      This paper summarizes the therapeutic rationale for Orzel and reviews the
      clinical experience with UFT and UFT/LV in combined modality therapy regimens.

PMID- 11241326
TI  - Overexpression of manganese superoxide dismutase (MnSOD) in whole lung or
      alveolar type II cells of MnSOD transgenic mice does not provide intrinsic lung
      irradiation protection.
AB  - Intratracheal (IT) injection of the transgene for human manganese superoxide
      dismutase in plasmid/liposome (SOD2-PL) complex prior to irradiation protects
      C57BL/6J mice from whole lung irradiation-induced organizing alveolitis/fibrosis.
      Transgene mRNA was detected in alveolar type II (AT-II) and tracheobronchial tree
      cells explanted to culture 48 hours after gene therapy. To determine whether
      constitutive overexpression of murine MnSOD (Sod2) in whole lung or surfactant
      promoter-restricted AT-II cells (SP1)-SOD2 mice would provide intrinsic
      radioresistance, transgenic mice of two strains were compared with age-matched
      controls. Other groups of surfactant promoter-restricted (SP1)-SOD2 transgenic
      mice or control FeVB/NHsd mice received IT SOD2-PL gene therapy prior to
      irradiation. There was no significant intrinsic lung protection in either strain
      of MnSOD transgenic mice. The SP1-SOD2 transgenic mice were protected from lung
      damage by IT injection of the human SOD2-PL complex 24 hours prior to
      irradiation. Thus, overexpression of either human SOD2 or murine Sod2 in the
      lungs of transgenic mice does not provide intrinsic lung irradiation protection.
      The overexpression of SOD2 in the SP1-SOD2 mice may have made the mice more
      sensitive to irradiation.

PMID- 11241328
TI  - Effect of low dose irradiation on estrogen receptor level in MCF-7 breast cancer
      cells.
AB  - Exposure of MCF-7 cells to single and/or repeated low gamma-ray doses (0.5 to 8
      Gy) resulted in a decrease in the capacity of these cells to concentrate
      tritiated estradiol ([3H]E2) (reduction of the number of binding sites). The
      decrease in the [3H]E2-binding capacity was higher than the survival rate,
      indicating that it could not be ascribed to cell death. Moreover, such low
      irradiation doses failed to similarly affect the specific incorporation of
      [3H]ORG 2058, even when the progesterone receptor was induced by E2, a finding
      that rejects the hypothesis of a nonspecific effect on all steroid hormone
      receptors. This loss of [3H]E2 binding was reflected by the elimination of the
      estrogen receptor alpha (ER) when the latter was assessed by immunocytochemistry.
      However, additional immunochemical studies (Western blot data) performed on cell
      extracts under denaturing conditions failed to show any similar elimination of
      the ER peptide, suggesting that the loss of E2-binding capacity would be relevant
      to subtle changes in the ER structure and/or ER-associated proteins. The loss of
      binding capacity, produced by a 3-Gy irradiation, failed to decrease the
      sensitivity of the cells to E2, since progesterone receptor induction and growth
      stimulation were maintained. Insufficient ER diminution may explain this
      observation.

PMID- 11241327
TI  - Activation of Gadd34 by diverse apoptotic signals and suppression of its growth
      inhibitory effects by apoptotic inhibitors.
AB  - DNA damage has many cellular consequences including, in some cases, apoptosis.
      Expression of Gadd34 was shown to be increased by ionizing radiation only in
      cells that undergo rapid apoptosis following this treatment. The effects of
      various other apoptosis-inducing agents as well as apoptosis-inhibiting genes on
      regulation of Gadd34 were investigated. In many cell types, agents which have
      been reported to lead to increased intracellular ceramide levels led to an
      increase in Gadd34 transcript levels. These included TNFalpha, the ceramide
      analog C-2 ceramide, dimethyl sphingosine and anti-Fas antibody as well as
      ionizing radiation. Induction of Gadd34 by ionizing radiation was coincident with
      the onset of apoptosis and increased as apoptosis progressed. In a short-term
      transfection assay, more than 30% of Gadd34-transfected cells exhibited nuclear
      fragmentation by 48 hours. Apoptosis, as well as induction of Gadd34 by apoptotic
      stimuli, was attenuated by the apoptosis inhibitors, Bcl-2, cowpox virus CrmA and
      herpes simplex virus ICP34.5. Thus, activation of Gadd34 is a downstream event in
      apoptotic signaling pathways and may directly contribute to the apoptotic
      process.

PMID- 11241330
TI  - Three-dimensional radiotherapy of head and neck and esophageal carcinomas: a
      monoisocentric treatment technique to achieve improved dose distributions.
AB  - The specific aim of three-dimensional conformal radiotherapy is to deliver
      adequate therapeutic radiation dose to the target volume while concomitantly
      keeping the dose to surrounding and intervening normal tissues to a minimum. The
      objective of this study is to examine dose distributions produced by various
      radiotherapy techniques used in managing head and neck tumors when the upper part
      of the esophagus is also involved. Treatment planning was performed with a three
      dimensional (3-D) treatment planning system. Computerized tomographic (CT) scans
      used by this system to generate isodose distributions and dose-volume histograms
      were obtained directly from the CT scanner, which is connected via ethernet
      cabling to the 3-D planning system. These are useful clinical tools for
      evaluating the dose distribution to the treatment volume, clinical target volume,
      gross tumor volume, and certain critical organs. Using 6 and 18 MV photon beams,
      different configurations of standard treatment techniques for head and neck and
      esophageal carcinoma were studied and the resulting dose distributions were
      analyzed. Film validation dosimetry in solid-water phantom was performed to
      assess the magnitude of dose inhomogeneity at the field junction. Real-time dose
      measurements on patients using diode dosimetry were made and compared with
      computed dose values. With regard to minimizing radiation dose to surrounding
      structures (i.e., lung, spinal cord, etc.), the monoisocentric technique gave the
      best isodose distributions in terms of dose uniformity. The mini-mantle anterior
      posterior/posterior-anterior (AP/PA) technique produced grossly non-uniform dose
      distribution with excessive hot spots. The dose measured on the patient during
      the treatment agrees to within +/- 5 % with the computed dose. The protocols
      presented in this work for simulation, immobilization and treatment planning of
      patients with head and neck and esophageal tumors provide the optimum dose
      distributions in the target volume with reduced irradiation of surrounding non
      target tissues, and can be routinely implemented in a radiation oncology
      department. The presence of a real-time dose-measuring system plays an important
      role in verifying the actual delivery of radiation dose.

PMID- 11241329
TI  - Involvement of the hepatocyte growth factor/scatter factor receptor c-met and of
      Bcl-xL in the resistance of oropharyngeal cancer to ionizing radiation.
AB  - The activation of cytoplasmic signal transduction pathways by a number of growth
      factors and their tyrosine-kinase receptors, including hepatocyte growth
      factor/scatter factor (HGF/SF) and its receptor c-met, exerts an inhibitory
      influence on apoptosis induced by ionizing radiation in vitro. The clinical
      relevance of the aforementioned ligand-receptor pair, of Bcl-xL, which is
      targeted by HGF/SF/c-met signaling, and of Bcl-2, was assessed by evaluating
      their predictive and prognostic impact in a cohort of 97 patients with radically
      irradiated squamous cell cancers of the oropharynx. Immunohistochemical
      expression of c-met and Bcl-xL was correlated with decreased rates of complete
      remission of the primary tumor in both the univariate (c-met: P = 0.01; Bcl-xL: P
      = 0.001) and multivariate analyses. Expression of c-met was, moreover, a
      significant and independent predictor of impaired local failure-free survival (P
      = 0.003), disease-free survival (P = 0.003) and overall survival (p = 0.001). Bcl
      2 expression was, on the other hand, associated with a favorable outcome, in
      terms of both local failure-free survival (P = 0.01) and overall survival (P =
      0.001). In accordance with in vitro data, c-met and Bcl-xL appear to be involved
      in the resistance of oropharyngeal cancers to ionizing radiation, and may
      therefore represent attractive targets for radiosensitization.

PMID- 11241331
TI  - Accuracy of contrast-enhanced computed tomography in the prediction of residual
      breast cancer after neoadjuvant chemotherapy.
AB  - Determination of the extent of residual disease after neoadjuvant chemotherapy is
      sometimes inaccurate by conventional diagnostic methods. The purpose of this
      study was to evaluate the accuracy of contrast-enhanced computed tomography (CE
      CT) in depicting the extent of residual carcinomas. Fifty-seven patients with
      breast carcinomas of 3 cm diameter or more received neoadjuvant chemotherapy with
      four cycles of AT (doxorubicin and docetaxel). Before surgery, the patients
      underwent clinical examination, mammogram (MMG), ultrasonography (US), and CE-CT.
      Thirteen patients were not evaluated by CE-CT before surgery. Enhancement
      patterns on CE-CT were classified into multiple spots, tumor and spots, solid
      tumor type, and no enhancement. When all types of cancers were included in the
      analysis, clinical examination showed the best correlation with the pathology of
      the extent of residual carcinomas. However, except in invasive lobular carcinoma
      (ILC) and inflammatory breast carcinoma (IBC), CE-CT showed the best correlation
      (R insertion mark2 = 0.537). More than half of the residual microcalcifications
      on MMG after neoadjuvant chemotherapy suggested residual viable tumor. In
      conclusion, CE-CT is the most accurate noninvasive technique for identifying the
      extent of the residual carcinoma after neoadjuvant chemotherapy if cases of IBC
      and ILC are excluded.

PMID- 11241332
TI  - Fixation strength of swellable bone anchors in low-density polyurethane foam.
AB  - This study represents a natural extension of our previous efforts in the design
      and development of a new class of swellable bone anchors, which absorb body
      fluids and achieve fixation by an expansion-fit mechanism. Specifically, this
      study investigates (i) correlations between the optimal swelling strain for
      highest fixation strength and the foam (or bone) density, and (ii) the influence
      of a threaded surface on the fixation strength of the swellable implant. For this
      purpose, the immediate and the final (after swelling) fixation strengths of two
      variations of the swellable bone anchor designs (a smooth anchor and a screw
      anchor) were measured in two different foams (used to simulate bone) with
      different densities. The amount of swelling was varied systematically for each
      foam and anchor design combinations. This study indicates that the screw
      swellable anchors have higher initial fixation strength than smooth swellable
      anchors, but the final fixation strengths of both anchors are quite similar.
      Further, it is observed that the optimal swelling strain decreased with
      increasing foam density. Both the smooth and screw swellable anchors were also
      found to exhibit higher fixation strengths than the metallic screws of similar
      geometry.

PMID- 11241334
TI  - The fretting corrosion resistance of PVD surface-modified orthopedic implant
      alloys.
AB  - The objective of this study was to evaluate the fretting corrosion resistance of
      both modified and unmodified Ti6Al4V flats fretted against CoCr-alloy spheres in
      a buffered Hank's solution at 37 degrees C using an original fretting apparatus.
      A physical vapor deposition (PVD) cathodic arc evaporation technique was used to
      deposit 3-4 microm thick titanium nitride (TiN), zirconium nitride (ZrN), or
      amorphous carbon (AC) coatings onto the Ti6Al4V substrates. The fretting behavior
      of the nitride films (TiN and ZrN) was characterized by the absence of surface
      damage and the deposition of a Cr-rich oxide transferred from the CoCr-alloy
      spheres to the modified surfaces. This oxide led to a slight increase in surface
      roughness. Three of the six multilayered AC coatings tested exhibited extensive
      fretting damage and generated large, deep, wear scars. Cohesive failure of the AC
      coating was observed in the low contact stress areas of the fretting scars. The
      remaining AC-coated specimens experienced only slight polishing wear. The reason
      for the different behavior within the AC-coated specimens is not clear at the
      present time. The unmodified Ti6Al4V surfaces experienced severe surface damage
      consistent with the adhesive galling mechanism to which these alloys are
      susceptible.

PMID- 11241333
TI  - Strain transfer between a CPC coated strain gauge and cortical bone during
      bending.
AB  - The finite element method was used to simulate strain transfer from bone to a
      calcium phosphate ceramic (CPC) coated strain gauge. The model was constructed
      using gross morphometric and histological measurements obtained from previous
      experimental studies. Material properties were assigned based on experiments and
      information from the literature. Boundary conditions simulated experimental
      cantilever loading of rat femora. The model was validated using analytical
      solutions based on the theory of elasticity as well as direct comparison to
      experimental data obtained in a separate study. The interface between the bone
      and strain gauge sensing surface consisted of layers of polysulfone,
      polysulfone/CPC, and CPC/bone. Parameter studies examined the effect of interface
      thickness and modulus, gauge geometry, partial gauge debonding, and waterproofing
      on the strain transfer from the bone to the gauge sensing element. Results
      demonstrated that interface thickness and modulus have a significant effect on
      strain transfer. Optimal strain transfer was achieved for an interface modulus of
      approximately 2 GPa. Strain transfer decreased consistently with increasing
      interface thickness. Debonding along the lateral edges of the gauge had little
      effect, while debonding proximal and distal to the sensing element decreased
      strain transfer. A waterproofing layer decreased strain transfer, and this effect
      was more pronounced as the modulus or thickness of the layer increased. Based on
      these simulations, specific recommendations were made to optimize strain transfer
      between bone and CPC coated gauges for experimental studies.

PMID- 11241335
TI  - Gamma-irradiated cross-linked polyethylene in total hip replacements--analysis of
      retrieved sockets after long-term implantation.
AB  - The purpose of this study was to evaluate the mechanical and chemical
      characteristics of gamma-irradiated, cross-linked polyethylene after long-term
      service in vivo. Two gamma-irradiated ultra high molecular weight polyethylene
      (RCH 1000, molecular weight: 10(6)) total hip replacement sockets were retrieved
      at 15 and 16 years after implantation. Mechanical and chemical characteristics of
      the sockets were evaluated in comparison with nonirradiated sockets. Significant
      surface oxidation occurred in the nonirradiated sockets; up to 75% of that seen
      in the irradiated ones. The mechanical properties of the irradiated sockets were
      not subject to increased deterioration in the presence of high free radical
      content. The cross-link was stable and was retained for a long period both in
      vivo and in ambient air. These data indicate that gamma-irradiated polyethylene
      was not subject to increased oxidative degradation during long-term service in
      vivo and confirmed the usefulness of this material as an articulating surface in
      total hip replacement.

PMID- 11241336
TI  - Control of pH alters the type of cross-linking produced by 1-ethyl-3-(3
      dimethylaminopropyl)-carbodiimide (EDC) treatment of acellular matrix vascular
      grafts.
AB  - Carbodiimide cross-linking of bioprosthetic materials has been shown to provide
      tissue stabilization equivalent to that of glutaraldehyde cross-linking, but
      without the risk of the release of unreacted or depolymerized cytotoxic reagent
      after implantation. In this study, the effects of 1-ethyl-3-(3
      dimethylaminopropyl)-carbodiimide (EDC) treatment on acellularized ovine carotid
      arteries were studied under two different pH conditions: (i) pH controlled at an
      optimal value of 5.5; and (ii) a simpler, but industrially significant,
      uncontrolled pH system. A multimode approach was employed involving biochemical
      assays, thermomechanical, tensile, and shear mechanical testing, and in vitro
      enzyme degradation analyses. EDC treatment decreased the hoop tangent modulus of
      acellular matrix (ACM) arterial grafts measured at 20 kPa of stress regardless of
      pH control. Extensibility of ACM arterial grafts measured at 20 kPa of stress was
      reduced after EDC treatment with pH control only. In contrast, shear stiffness of
      ACM arterial grafts increased to a greater degree under cross-linking without pH
      control (21 x compared to 14 x with pH control). Thermomechanical analyses
      revealed that EDC cross-linking with pH control also increased the collagen
      denaturation temperature of ACM arteries to a greater degree (a rise of 24.3 +/-
      0.6 degrees C vs. 21.7 +/- 0.7 degrees C for no pH control), whereas cross
      linking without pH control consumed a larger amount of lysine residues after 3 h
      of treatment. Most interestingly, both EDC treatments were equally effective in
      stabilizing ACM arteries against multiple degradative enzymes in vitro. The
      observed differences between EDC treatments under different pH conditions are
      attributed to differences in the location and types of the exogenous cross-links
      formed. The absence of pH control may have favored the formation of
      interfibrillar or intermolecular cross-links in collagen as well as involvement
      of other extracellular matrix components (proteoglycans and glycosaminoglycans).
      Furthermore, it may be emphasized that the location or type of cross-links
      differentially affected the mechanical behavior of treated materials without
      affecting the increase in resistance to enzymatic degradation.

PMID- 11241337
TI  - Structure, metallurgy, and mechanical properties of a porous tantalum foam.
AB  - This study evaluated a porous tantalum biomaterial (Hedrocel) designed to
      function as a scaffold for osseous ingrowth. Samples were characterized for
      structure, Vickers microhardness, compressive cantilever bending, and tensile
      properties, as well as compressive and cantilever bending fatigue. The structure
      consisted of regularly arranged cells having struts with a vitreous carbon core
      with layers of CVI deposited crystalline tantalum. Microhardness values ranged
      from 240-393, compressive strength was 60 +/- 18 MPa, tensile strength was 63 +/-
      6 MPa, and bending strength was 110 +/- 14 MPa. The compressive fatigue endurance
      limit was 23 MPa at 5 x 10(6) cycles with samples exhibiting significant plastic
      deformation. SEM examination showed cracking at strut junctions 45 degrees to the
      axis of the applied load. The cantilever bending fatigue endurance limit was 35
      MPa at 5 x 10(6) cycles, and SEM examination showed failure due to cracking of
      the struts on the tension side of the sample. While properties were variable due
      to morphology, results indicate that the material provides structural support
      while bone ingrowth is occurring. These findings, coupled with the superior
      biocompatibility of tantalum, makes the material a candidate for a number of
      clinical applications and warrants further and continued laboratory and clinical
      investigation.

PMID- 11241338
TI  - A simple method of determining the modulus of orthopedic bone cement.
AB  - Accurate determination of the elastic modulus of surgical bone cements is of
      primary importance, when evaluating the stresses within the cement mantle in
      Total Joint Arthroplasty. This article presents a new method of determining the
      modulus of surgical bone cements from the biaxial flexural test. The biaxial
      flexural test is not currently employed in mainstream orthopedic mechanical
      testing, which is surprising because most loading in orthopedic applications is
      biaxial in nature. Nor has this method been utilized for dental materials, even
      though the biaxial flexure test has been used for many years in this field. It
      has been demonstrated that the modulus of surgical bone cements can be determined
      from the biaxial flexural test, and these results are in agreement with results
      from compressive and bending tests.

PMID- 11241339
TI  - Comparison of UHMWPE particles in synovial fluid and tissues from failed THA.
AB  - The size and morphology of ultra high molecular weight polyethylene (UHMWPE) wear
      particles isolated from synovial fluid and periprosthetic tissues from three
      failed total hip arthroplasties were evaluated. Hip capsule, femoral canal
      tissue, and synovial fluid were collected at the time of revision surgery. The
      polyethylene wear particles were isolated and then imaged using a scanning
      electron microscope. The size and morphology of the particles were quantified
      using an image analysis protocol. Five shape descriptors were defined for each
      particle: equivalent circle diameter (ECD, a measure of size having units of
      length), aspect ratio (AR), elongation (E), roundness (R), and form factor (FF).
      The size and shape of the polyethylene particles differed depending on the
      source. Femoral tissue particles had the lowest equivalent circle diameter (0.697
      +/- 0.009 mm), aspect ratio (1.577 +/- 0.016), and elongation (1.912 +/- 0.030),
      but the highest values for roundness (0.715 +/- 0.005) and form factor (0.874 +/-
      0.003). Hip capsule particles had the highest equivalent circle diameter (0.914
      +/- 0.019 mm), aspect ratio (1.764 +/- 0.025), and elongation (2.488 +/- 0.053),
      but the lowest values for roundness (0.642 +/- 0.006) and form factor (0.803 +/-
      0.005). The size and shape descriptors for synovial fluid particles (equivalent
      circle diameter: 0.763 +/- 0.012 mm; aspect ratio: 1.700 +/- 0.029; elongation:
      2.212 +/- 0.054; roundness: 0.681 +/- 0.006; and form factor: 0.841 +/- 0.004)
      were intermediate among the femoral tissue and hip capsule particles. These data
      suggest that larger particles may become lodged in the hip capsule, while smaller
      particles may migrate to more distant tissues and subsequently cause aseptic
      loosening and osteolysis.

PMID- 11241340
TI  - Reinforcement of acrylic denture base resin by incorporation of various fibers.
AB  - This study was designed to evaluate improvements in the mechanical properties of
      acrylic resin following reinforcement with three types of fiber. Polyester fiber
      (PE), Kevlar fiber (KF), and glass fiber (GF) were cut into 2, 4, and 6 mm
      lengths and incorporated at concentrations of 1, 2, and 3% (w/w). The mixtures of
      resin and fiber were cured at 70 degrees C in a water bath for 13 h, then at 90
      degrees C for 1 h, in 70 x 25 x 15 mm stone molds, which were enclosed by dental
      flasks. The cured resin blocks were cut to an appropriate size and tested for
      impact strength and bending strength following the methods of ASTM Specification
      No. 256 and ISO Specification No. 1567, respectively. Specimens used in the
      impact strength test were reused for the Knoop hardness test. The results showed
      that the impact strength tended to be enhanced with fiber length and
      concentration, particularly PE at 3% and 6 mm length, which was significantly
      stronger than other formulations. Bending strength did not change significantly
      with the various formulations when compared to a control without fiber. The
      assessment of Knoop hardness revealed a complex pattern for the various
      formulations. The Knoop hardness of 3%, 6 mm PE-reinforced resin was comparable
      to that of the other formulations except for the control without fiber, but for
      clinical usage this did not adversely affect the merit of acrylic denture base
      resin. It is concluded that, for improved strength the optimum formulation to
      reinforce acrylic resin is by incorporation of 3%, 6 mm length PE fibers.

PMID- 11241341
TI  - Elution of bisphenol-A from hemodialyzers consisting of polycarbonate and
      polysulfone resins.
AB  - This study deals with bisphenol-A (BPA) analysis of the BPA-derived polymer
      pellets, polycarbonate (PC) and polysulfone (PS), and in the hemodialyzer casings
      made of PC, and the leaching of BPA from commercially available hemodialyzers
      into water and bovine serum, using HPLC, GC-MS, and LC-MS analyses, and NMR
      spectroscopy. Total contents of BPA in polymer pellets of each resin were 4.0 and
      7.2 microg/g (PC) and 34.5 microg/g (PS). Amounts of BPA released from
      hemodialyzer PC casings lacking PS hollow-fiber were 11.7 and 13.7 ng/casing by
      water extraction, and 296 and 345 ng/casing by methanol extraction. On the other
      hand, BPA of 3.78 to 141.8 ng/module was recovered using water circulation of
      hemodialyzers, and 140.7 to 2,090 ng/module was detected when bovine serum was
      used as a circulation solvent. The elution profiles using various concentrations
      of ethanol/water mixtures indicated that a 17.2% (v/v) ethanol solution rather
      than bovine serum can be used as an extraction solvent, where a similar amount of
      BPA as with bovine serum circulation was eluted from the hemodialyzer. Thus, this
      solvent may be useful for evaluating BPA elution from hemodialyers under similar
      conditions to medical use.

PMID- 11241344
TI  - Ubiquitin-mediated proteolysis of vertebrate G1- and S-phase regulators.
AB  - Cell-cycle progression in all eukaryotes is driven by cyclin-dependent kinases
      (CDKs) and their cyclin partners. In vertebrates, the proper and timely
      duplication of the genome during S-phase relies on the coordinated activities of
      positive regulators such as CDK-cyclins and E2F, and negative regulators such as
      CDK inhibitors of the Cip/Kip and INK4 families. Recent and ongoing work
      indicates that many important regulators of G1- and S-phases are targeted for
      ubiquitination and subsequent degradation by the 26S proteasome. The proteolysis
      of key proteins during G1- and S-phases appears to be central for proper
      custodial regulation of DNA replication and the maintenance of cellular
      homeostasis in general. This review highlights the current literature regarding
      ubiquitin-mediated proteolysis of G1- and S-phase regulators and the control of
      events during the initiation and completion of DNA replication in vertebrates.

PMID- 11241346
TI  - Gene directed enzyme/prodrug therapy of cancer: historical appraisal and future
      prospectives.
AB  - Gene therapy of cancer is a novel approach with the potential to selectively
      eradicate tumour cells, whilst sparing normal tissue from damage. In particular,
      gene-directed enzyme prodrug therapy (GDEPT) is based on the delivery of a gene
      that encodes an enzyme which is non-toxic per se, but is able to convert a
      prodrug into a potent cytotoxin. Several GDEPT systems have been investigated so
      far, demonstrating effectiveness in both tissue culture and animal models. Based
      on these encouraging results, phase I/II clinical trials have been performed and
      are still ongoing. The aim of this review is to summarise the progress made in
      the design and application of GDEPT strategies. The most widely used
      enzyme/prodrug combinations already in clinical trials (e.g., herpes simplex 1
      virus thymidine kinase/ganciclovir and cytosine deaminase/5-fluorocytosine), as
      well as novel approaches (carboxypeptidase G2/CMDA, horseradish peroxidase/indole
      3-acetic acid) are described, with a particular attention to translational
      research and early clinical results.

PMID- 11241347
TI  - Matrix metalloproteinase expression by endothelial cells in collagen lattices
      changes during co-culture with fibroblasts and upon induction of decorin
      expression.
AB  - EA.hy 926 cells, a derivative of human umbilical vein endothelial cells, in the
      presence of fibroblasts show the phenomena of angiogenesis, express the
      proteoglycan decorin and escape apoptosis, when they are maintained in collagen
      lattices, while fibroblast-free cultures do not show these changes. Virus
      mediated decorin expression can substitute for the presence of fibroblasts. Since
      the expression of matrix metalloproteinases (MMPs) is an essential step in the
      formation of capillaries, several MMPs and tissue inhibitors of
      metalloproteinases (TIMPs) were investigated. MMP-1, MMP-2, MMP-9, and the cell
      associated MMP-14 were augmented on the protein level in the presence of
      fibroblasts. No effect was seen with respect to MMP-3, TIMP-1, and TIMP-2.
      Semiquantitative RT-PCRs of endothelial cells in co-culture revealed a 7-, 19-,
      and 11-fold increase for mRNAs of MMP-1, MMP-2, and MMP-14 after six days,
      respectively. Virus-mediated decorin expression also was accompanied by an up
      regulation of these MMPs. The expression of MMP-1 mRNAs increased 5-fold after 2
      days and gradually declined thereafter. In contrast, MMP-2 and MMP-14 showed a 7
      fold and a 14-fold increase on day two which returned to basal levels within 24
      h, indicating that the expression of MMP-1 is differentially regulated from MMP-2
      and MMP-14. In spite of the upregulation of the proteases, an enhanced
      degradation of decorin was not observed. These results indicate that the
      expression of decorin is a sufficient signal in EA.hy 926 cells for a finely
      tuned induction of selected MMPs which are involved in angiogenesis whereas the
      up-regulation of MMPs does not lead to the degradation of the responsible
      proteoglycan.

PMID- 11241345
TI  - Eukaryotic ribonuclease P: increased complexity to cope with the nuclear pre-tRNA
      pathway.
AB  - Ribonuclease P is an ancient enzyme that cleaves pre-tRNAs to generate mature 5'
      ends. It contains an essential RNA subunit in Bacteria, Archaea, and Eukarya, but
      the degree to which the RNA subunit relies on proteins to supplement catalysis is
      highly variable. The eukaryotic nuclear holoenzyme has recently been found to
      contain almost twenty times the protein content of the bacterial enzymes, in
      addition to having split into at least two related enzymes with distinct
      substrate specificity. In this review, recent progress in understanding the
      molecular architecture and functions of nuclear forms of RNase P will be
      considered.

PMID- 11241348
TI  - Starvation-induced lysosomal degradation of aldolase B requires glutamine 111 in
      a signal sequence for chaperone-mediated transport.
AB  - Aldolase B is an abundant cytosolic protein found in all eukaryotic cells. Like
      many glycolytic enzymes, this protein was sequestered into lysosomes for
      degradation during nutrient starvation. We report here that the degradation of
      recombinant aldolase B was enhanced two-fold when rat and human hepatoma cells
      were starved for amino acid and serum. In addition, starvation-induced
      degradation of aldolase B was inhibited by chloroquine, an inhibitor of lysosomal
      proteinases and by 3-methyladenine, an inhibitor of autophagy. Aldolase B has
      three lysosomal targeting motifs (Q(12)KKEL, Q(58)FREL, and IKLDQ(111)) that have
      been proposed to interact with hsc73 thereby initiating its transport into
      lysosomes. In this study, we have mutated the essential glutamine residues in
      each of these hsc73-binding motifs in order to evaluate their roles in the
      lysosomal degradation of aldolase B during starvation. We have found that when
      glutamines 12 or 58 are mutated to asparagines enhanced degradation of aldolase B
      proceeded normally. However, when glutamine 111 was mutated to an asparagine or a
      threonine, starvation-induced degradation was completely suppressed. These
      mutations did not appear to alter the tertiary structure of aldolase B since
      enzymatic activity was not affected. Our results suggest that starvation-induced
      lysosomal degradation of aldolase B requires both autophagy and glutamine 111. We
      discuss the possible roles for autophagy and hsc73-mediated transport in the
      lysosomal sequestration of aldolase B.

PMID- 11241349
TI  - Pleiotrophin induces angiogenesis: involvement of the phosphoinositide-3 kinase
      but not the nitric oxide synthase pathways.
AB  - Pleiotrophin (PTN) is a developmentally regulated protein that has been shown to
      be involved in tumor growth and metastasis presumably by activating tumor
      angiogenesis. To clarify the potential angiogenic activity of PTN and to analyze
      the signaling pathways involved in this process, we used an in vitro model of
      Human Umbilical Vein Endothelial Cells (HUVEC). We show that PTN was mitogenic
      toward a variety of endothelial cells including HUVEC, stimulated HUVEC migration
      across a reconstituted basement membrane and induced the formation of capillary
      like structures by HUVEC grown as 3D-cultures in Matrigel or collagen. The
      signaling pathways triggered following endothelial cell stimulation by PTN were
      studied by using pharmacological inhibitors of the Phosphoinositide-3 kinase
      (PI3K) and endothelial Nitric Oxide Synthase (eNOS), two enzymes that have been
      shown to be crucial in the angiogenic response to Vascular Endothelial Growth
      Factor (VEGF). Whereas wortmannin (a PI3K inhibitor) and L-NAME (an eNOS
      inhibitor) dramatically reduced HUVEC growth induced by VEGF, only the former
      inhibitor reduced the growth induced by PTN and to a lesser extent that
      stimulated by basic Fibroblast Growth Factor. Thus, our results indicate that PTN
      induces angiogenesis and utilizes PI3K- but not eNOS-dependent pathways for its
      angiogenic activity.

PMID- 11241350
TI  - Cell cycle-related changes in regulatory volume decrease and volume-sensitive
      chloride conductance in mouse fibroblasts.
AB  - Cell cycle-related changes in the ability to regulate cell volume following
      hyposmotic swelling were studied in mouse fibroblasts using videomicroscopy and
      the whole-cell patch clamp technique. Regulatory volume decrease (RVD) and volume
      sensitive Cl- conductance (G(Cl,vol)) were measured: (1) in proliferating cells
      of different sizes; (2) in cells arrested in defined phases of the cell cycle
      (G1, G1/S, S, and M phases) using mevastatin, mimosine, hydroxyurea, aphidicolin,
      cytosine beta-D-arabinofuranoside, and taxol; and (3) in serum-starved cells
      (G(0) state). Cells in all groups were able to undergo RVD, although the cells
      approaching mitosis (i.e., the largest cells in proliferating cultures and the
      taxol-treated cells) had the lowest rates of shrinkage during RVD. In agreement
      with this finding, the density of G(Cl,vol) was stable in proliferating and cell
      cycle-arrested cells for most of the cell cycle, with the exception of the cells
      approaching mitosis and the new daughter cells where the density was decreased to
      half. The impairment of RVD was greatest in serum-starved cells which also had
      the lowest density of G(Cl,vol). We conclude that proliferating cells maintain an
      ability to recover from osmotic swelling as they progress through the cell cycle,
      although this ability may be compromised during mitosis.

PMID- 11241351
TI  - Skeletal muscle cell activation by low-energy laser irradiation: a role for the
      MAPK/ERK pathway.
AB  - Low-energy laser irradiation (LELI) has been shown to promote skeletal muscle
      regeneration in vivo and to activate skeletal muscle satellite cells, enhance
      their proliferation and inhibit differentiation in vitro. In the present study,
      LELI, as well as the addition of serum to serum-starved myoblasts, restored their
      proliferation, whereas myogenic differentiation remained low. LELI induced
      mitogen-activated protein kinase/extracellular signal-regulated protein kinase
      (MAPK/ERK) phosphorylation with no effect on its expression in serum-starved
      myoblasts. Moreover, a specific MAPK kinase inhibitor (PD098059) inhibited the
      LELI- and 10% serummediated ERK1/2 activation. However, LELI did not affect Jun N
      terminal kinase (JNK) or p38 MAPK phosphorylation or protein expression. Whereas
      a 3-sec irradiation induced ERK1/2 phosphorylation, a 12-sec irradiation reduced
      it, again with no effect on JNK or p38. Moreover, LELI had distinct effects on
      receptor phosphorylation: it caused phosphorylation of the hepatocyte growth
      factor (HGF) receptor, previously shown to activate the MAPK/ERK pathway, whereas
      no effect was observed on tumor suppressor necrosis alpha (TNF-alpha) receptor
      which activates the p38 and JNK pathways. Therefore, by specifically activating
      MAPK/ERK, but not JNK and p38 MAPK enzymes, probably by specific receptor
      phosphorylation, LELI induces the activation and proliferation of quiescent
      satellite cells and delays their differentiation.

PMID- 11241352
TI  - Estrogen and estrogen plus progestin act directly on the mammary gland to
      increase proliferation in a postmenopausal mouse model.
AB  - Hormone replacement therapy (HRT) with ovarian hormones is an important
      therapeutic modality for postmenopausal women. However, a negative side effect of
      HRT is an increased risk of breast cancer. Surgical induction of menopause by
      ovariectomy (OVX) in mice is an experimental model that may provide insights into
      the effects of hormone replacement therapy on the human breast. We have developed
      a mouse model of early and late postmenopausal states to investigate the effects
      of HRT on the normal mammary gland. The purpose of this study was to determine if
      HRT-induced proliferation was due to the direct action of the hormones on the
      mammary gland, or mediated systemically by hormones or growth factors produced
      elsewhere in the body. Estrogen (E) or E plus the synthetic progestin, R5020,
      were implanted directly into the mammary glands of early (1 week post OVX) and
      late (5 week post OVX) postmenopausal mice instead of administration by
      injection. We report that responses of early and late postmenopausal mice to
      implanted hormones were the same as those observed previously with systemically
      administered hormones. Implanted E conferred an enhanced proliferative response
      in the late postmenopausal gland characterized morphologically by enlarged duct
      ends. E+R5020 implants induced similar degrees of cell proliferation in both
      postmenopausal states but the morphological responses differed. Ductal
      sidebranching was observed in early postmenopausal mice, whereas duct end
      enlargement was observed in late postmenopausal mice. The differences in
      morphological response to E+R5020 in 5 week post OVX were associated with an
      inability of E to induce progesterone receptors (PR) in the late postmenopausal
      gland. The responses of the late postmenopausal glands to E and E+P were very
      similar to that observed previously in immature pubertal glands in ovary-intact
      mice. In pubertal mice, PR cannot be induced by E unless the mammary gland is pre
      treated with EGF-containing implants. Similarly, herein pre-treatment of the late
      postmenopausal mammary gland with EGF-containing implants restored PR induction
      by E. Thus, EGF may determine the sensitivity of the mammary gland to E and E+P
      in late postmenopause and at puberty.

PMID- 11241353
TI  - Anabolic-androgenic steroids induce apoptotic cell death in adult rat ventricular
      myocytes.
AB  - We tested whether exposure to anabolic-androgenic steroids (AASs) would induce
      apoptosis in adult rat ventricular myocytes in vitro. Myocytes were exposed to
      stanozolol (STZ), testosterone enanthate (TE) and testosterone (T) (0.1
      micromol/L, 1 micromol/L, 10 micromol/L, and 100 micromol/L) for 20 h. The
      percentage of myocytes undergoing apoptosis was determined by terminal
      deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) and was found to
      be increased when compared to control myocytes at STZ 10 micromol/L 12 +/- 2%
      (mean +/- SD), STZ 100 micromol/L 42 +/- 3%; TE 1 micromol/L 11 +/- 2%, TE 10
      micromol/L 21 +/- 3%, TE 100 micromol/L 62 +/- 2%; T 10 micromol/L 11 +/- 2%, T
      100 micromol/L 40 +/- 3% (P < 0.001 vs. CTL 2 +/- 2%). The STZ-, TE- and T
      induced dose-dependent apoptotic cell death was corroborated by a significantly
      increased DNA laddering in myocytes exposed to STZ and T > or = 10 micromol/L and
      TE > or = 1 micromol/L. Notably, STZ, TE, and T exposure markedly increased the
      expression of the pro-apoptotic oncogene Bax-alpha, as assessed by reverse
      transcription-polymerase chain reaction. Taken together, these results clearly
      show for the first time that AASs induce apoptotic cell death in a dose-dependent
      manner. This finding may have important implications in understanding the
      pathogenesis of ventricular remodeling, cardiomyopathy, and sudden cardiac death
      associated with AAS abuse.

PMID- 11241354
TI  - Insulin signaling leading to proliferation, survival, and membrane ruffling in
      C2C12 myoblasts.
AB  - We have recently shown that insulin induced myogenesis in the mouse C2C12
      skeletal muscle cell line by activation of phosphatidylinositol (PI) 3
      kinase/p70S6-kinase and p38-mitogen-activated protein kinase (MAPK) and
      downregulation of p42/p44-MAPK. This study investigated the insulin-signaling
      pathways involved in mitogenesis, survival, and membrane ruffling in C2C12
      myoblasts, a cellular system that besides IGF-I receptors, expressed a high
      number of functional insulin receptors. Insulin (10 nM) rapidly stimulated beta
      chain insulin receptor and IRS-1 tyrosine phosphorylation, IRS-2 being poorly and
      SHC not phosphorylated at all. However, an association of SHC with IRS-1 was
      found under insulin stimulation. Insulin stimulated IRS-1 association with
      p85alpha leading to the activation of PI3-kinase, and, subsequently AKT and p70S6
      kinases. Moreover, both p42/p44- and p38-MAPKs resulted in phosphorylation after
      insulin stimulation. Insulin treatment for 24 h produced mitogenesis, as
      demonstrated by the increase in ((3)H)-thymidine incorporation, DNA content, the
      expression of PCNA and cyclin D1 proteins, and the proportion of cells in S +
      G2/M phases of the cell cycle. This mitogenic effect of insulin was precluded by
      inhibition of p70S6-kinase (either by rapamycin or by the PI3-kinase inhibitor
      LY294002) as well as by inhibition of p44/p42-MAPK with PD098059, but was not
      affected by inhibition of p38-MAPK. Serum deprivation of C2C12 myoblasts resulted
      in growth arrest at the GO/G1 phases of the cell cycle and apoptosis, as detected
      either by DNA laddering or by increase in the percentage of hypodiploid cells.
      Insulin rescued serum-deprived cells from apoptosis in an AKT-dependent manner,
      as demonstrated by the inhibition of AKT-activity by the use of LY294002 and ML
      9, meanwhile neither inhibition of p70S6-kinase, nor MAPK affected insulin
      induced survival. Finally, we evaluated the capacity of insulin to modulate actin
      cytoskeleton rearrangement. Insulin stimulation of myoblasts produced membrane
      ruffling and decreased actin stress fibers; this biological response being
      dependent of p38-MAPK, as demonstrated by the use of the p38-MAPK inhibitors
      SB203580 or PD169316, but independent of PI3-kinase and p42/p44-MAPK.

PMID- 11241355
TI  - Roles of ATP and cytoskeleton in the regulation of Na+/H+ exchanger along the
      nephron luminal membrane.
AB  - Although in LLC-PK cells ATP depletion has been shown to result in alterations of
      cytoskeleton actin and an inhibition of Na+/H+ exchanger activity, there is
      little information concerning the regulation of this exchanger in the distal
      luminal membrane by ATP and actin filaments. The present study examined the
      direct effect of ATP and cytochalasin B on the Na+/H+ exchanger activity in the
      proximal and distal tubule luminal membranes. The presence of 100 microM ATP in
      the luminal membrane vesicles from rabbit proximal tubules did not influence the
      Ethyl Isopropyl Amiloride sensitive Na+ uptake by these membranes. In contrast,
      the same treatment of luminal membranes from distal tubules significantly
      enhanced the exchanger activity from 0.22 +/- 0.04 to 0.39 +/- 0.08 pM/microg/10
      sec (P < 0.02). When ATP was replaced by its nonhydrolysable form, ATPgammas, the
      effect on the distal luminal membrane was strongly diminished suggesting that the
      action of the nucleotide implicates a phosphorylation step. Confirming this
      hypothesis, addition of 300-microM-Rp cAMP, a protein kinase A inhibitor,
      completely abolished the effect of ATP. In view of the fact that a tight
      relationship has been described between ATP, the cytoskeleton complex and the
      exchanger activity, we studied the effect of cytochalasin B on this activity. The
      presence of 20 microM cytochalasin B in the distal luminal membrane vesicles
      induced, as observed with ATP, a significant increase in the Na+ uptake. However,
      the actions of ATP and cytochalasin B were not additive. These results suggest
      that firstly, ATP and short actin filaments of the cytoskeleton regulate the
      distal luminal isoform through an intramembranous mechanism and secondly, a
      phosphorylation mechanism is, at least partially, implicated in the action of
      ATP. In contrast, the proximal tubule exchanger is regulated through different
      mechanisms.

PMID- 11241356
TI  - Constitutive phosphorylation and nuclear localization of Smad3 are correlated
      with increased collagen gene transcription in activated hepatic stellate cells.
AB  - Hepatic stellate cells (HSC) are the main producers of type I collagen in
      fibrotic liver, and transforming growth factor-beta (TGF-beta) plays critical
      roles in stimulating collagen gene expression in the cells mainly at the level of
      transcription. We have previously identified an upstream sequence of alpha2(I)
      collagen gene (COL1A2) that is essential for its basal and TGF-beta-stimulated
      transcription in skin fibroblasts and HSC. We designated this region the TGF-beta
      responsive element (TbRE). Recently Smad3, an intracellular mediator of TGF-beta
      signal transduction, has been shown to bind to the TbRE and stimulate COL1A2
      transcription when overexpressed in skin fibroblasts. In the present study, we
      demonstrate increased transcription of COL1A2 and plasminogen activator inhibitor
      1 (PAI-1) genes and low response to TGF-beta in an activated HSC clone derived
      from a cirrhotic liver. Western blot analyses indicated constitutive
      phosphorylation of Smad3 in the cells. Immunofluorescence studies revealed that,
      in contrast to Smad2 that translocated from the cytoplasm to the nucleus upon TGF
      beta treatment, Smad3 and Smad4 were present in the nucleus irrespective of
      ligand stimulation. Increased COL1A2 and PAI-1 gene transcription in the cells
      was not affected by overexpression of inhibitory Smad7. Altogether, the results
      correlate abnormality in TGF-beta/Smad signaling with pathologically accelerated
      collagen gene transcription in activated HSC.

PMID- 11241357
TI  - A new molecular role for iron in regulation of cell cycling and differentiation
      of HL-60 human leukemia cells: iron is required for transcription of
      p21(WAF1/CIP1) in cells induced by phorbol myristate acetate.
AB  - To investigate the role of iron in hematopoiesis, we studied effects of iron
      deprivation on PMA-induced monocyte/macrophage differentiation in HL-60 cells.
      Iron deprivation induced by desferrioxamine (DF) blocked PMA-induced
      differentiation and induced S-phase arrest and apoptosis in up to 60% of cells.
      Apoptosis was not related to a decrease of bcl-2 or to c-myc overexpression. In
      the presence of DF, PMA-induced upregulation of the cyclin dependent kinase
      inhibitor (CDKI), p21(WAF1/CIP1), was blocked and its expression could be
      restored in the presence of DF by supplementation with ferric citrate.
      Furthermore, ferrioxamine (iron saturated DF) did not block induction of
      p21(WAF1/CIP1) indicating that the changes were not due to a nonspecific toxic
      effect of DF. Similarly, hydroxyurea, an inhibitor of ribonucleotide reductase,
      did not block p21 expression. p21(WAF1/CIP1) antisense oligonucleotides caused
      cell cycle alterations similar to DF and p21 overexpression overcame effects of
      iron deprivation on both cell cycling and differentiation. Therefore, p21 is a
      key target for the effects of iron deprivation on HL-60 cell cycling and
      differentiation. Nuclear run-on transcription assays and p21 mRNA half-life
      studies indicated that iron was required to support transcriptional activation of
      p21(WAF1/CIP1) after a PMA stimulus. By contrast, iron deprivation did not
      inhibit expression of a second CDKI, p27(KIP1). These data demonstrate a new role
      for iron during monocyte/macrophage differentiation. A key role of iron is to
      allow induction of p21(WAF1/CIP1) in response to a differentiation stimulus
      subsequently blocking cells at the G(1)/S cell cycle interface and preventing
      premature apoptosis. This effect of iron is independent of its requirement in
      supporting the activity of the enzyme, ribonucleotide reductase. Because of the
      central role of p21(WAF1/CIP1) as regulator of the G(1)/S cell cycle checkpoint
      this requirement for iron to support p21 expression represents an important
      mechanism by which iron may modulate hematopoietic cell growth and
      differentiation. Published 2001 Wiley-Liss, Inc.

PMID- 11241359
TI  - Outpatient mental health care, self-help groups, and patients' one-year treatment
      outcomes.
AB  - OBJECTIVE: To examine the association between the duration and amount of
      outpatient mental health care, participation in self-help groups, and patients'
      casemix-adjusted one-year outcomes. METHODS: A total of 2,376 patients with
      substance use disorders, 35% of whom also had psychiatric disorders, were
      assessed at entry to treatment and at a one-year follow-up. Information about the
      duration and amount of outpatient mental health care was obtained from a
      centralized health services utilization database. RESULTS: Patients who obtained
      regular outpatient mental health care over a longer interval and patients who
      attended more self-help group meetings had better one-year substance use and
      social functioning outcomes than did patients who were less involved in formal
      and informal care. The amount of outpatient mental health care did not
      independently predict one-year outcomes. CONCLUSIONS: The duration of outpatient
      mental health care and the level of self-help involvement are independently
      associated with less substance use and more positive social functioning. The
      provision of low intensity treatment for a longer time interval may be a cost
      effective way to enhance substance abuse and psychiatric patients' long-term
      outcomes.

PMID- 11241360
TI  - The dependent patient in a psychiatric inpatient setting: relationship of
      interpersonal dependency to consultation and medication frequencies.
AB  - To examine the relationship between interpersonal dependency and medical service
      use in a hospital setting, the number of medical consultations and psychotropic
      medication prescriptions were compared in matched, mixed-sex samples of 40
      dependent and 40 nondependent psychiatric inpatients. Results indicated that
      dependent patients received more medical consultations and a greater number of
      medications than did nondependent patients with similar demographic and
      diagnostic profiles. Implications of these results for theoretical models of
      interpersonal dependency and for previous research on the dependency-help-seeking
      relationship are discussed. Practical implications of these findings for work
      with dependent patients are summarized.

PMID- 11241361
TI  - Coping style of substance-abuse patients: effects of anxiety and mood disorders
      on coping change.
AB  - The authors studied the coping style of substance-abuse patients during clinical
      cognitive-behavioral group therapy, and the effects of mood and anxiety disorders
      on changes in coping style. Change in coping style was studied prospectively in a
      cohort of 132 residential-drug-abuse patients. In addition to pretreatment
      assessments, which included diagnosis of mood and anxiety disorders and addiction
      severity, repeated measurements of coping style were performed at
      predetoxification, pretreatment, and after three and six months of treatment.
      Considerable change in coping style between predetoxification and pretreatment
      was found, suggesting that coping assessment in a predetoxification phase is
      confounded by state factors surrounding treatment entry. Coping style of
      detoxified substance abusers is related to the presence of mood and anxiety
      disorders. Coping style was not found to be related to the severity of drug
      abuse. Furthermore, maladaptive coping styles decreased after three months of
      inpatient-substance-abuse treatment, and more-adaptive coping styles remained
      stable for another three months of inpatient treatment. Patients with an anxiety
      disorder improved less on coping style when compared to non-anxiety patients.
      Presence of a mood disorder had no impact on coping-style improvement. The
      results indicate that more attention should be focused on anxiety disorders
      during substance-abuse treatment in order to improve coping style. Furthermore,
      more studies are needed on the relation between substance abuse, coping style,
      and psychopathology.

PMID- 11241362
TI  - A cognitive-interpersonal case study of a self.
AB  - This article presents an integrated conception of the self based on cognitive and
      interpersonal theories. Implications for clinical practice are outlined, which
      include understanding the therapeutic relationship as a laboratory and change as
      involving self-expansion. Implications for clinical research are also presented
      and exemplified by two strategies, which are demonstrated in a single case study
      of a patient who successfully underwent a brief-term treatment. The first
      involves the use of Interpersonal Scenarios, which are structured idiographic
      vignettes scaled on several parameters, to measure change between psychotherapy
      sessions. The second involves the use of the Structural Analysis of Social
      Behavior, a measure of interpersonal process, and the Experiencing Scale, a
      measure of emotional involvement, to measure change within a session.

PMID- 11241364
TI  - Irrational beliefs, attitudes about competition, and splitting.
AB  - Rational-Emotive Behavior Therapy (REBT) theoretically promotes actualization of
      both individualistic and social-oriented potentials. In a test of this
      assumption, the Belief Scale and subscales from the Survey of Personal Beliefs
      served as measures of what REBT presumes to be pathogenic irrationalities. These
      measures were correlated with the Hypercompetitive Attitude Scale (HCAS), the
      Personal Development Competitive Attitude Scale (PDCAS), factors from the
      Splitting Index, and self-esteem. Results for the HCAS and Self-Splitting
      supported the REBT claim about individualistic self-actualization. Mostly
      nonsignificant and a few counterintuitive linkages were observed for irrational
      beliefs with the PDCAS, Family-Splitting, and Other-Splitting, and these data
      suggested that REBT may be less successful in capturing the "rationality" of a
      social-oriented self-actualization.

PMID- 11241363
TI  - The relationship between dissociative tendencies and schizotypy: an artifact of
      childhood trauma?
AB  - Previous research has suggested a relationship between dissociative tendencies
      and schizotypy. This study sought to extend the previous work in two fundamental
      respects. First, explicit cognizance was taken of the multidimensionality of both
      dissociative tendencies and schizotypy. Second, the study examined the
      possibility that the observed correlation between dissociative tendencies and
      schizotypy is an artifact of the association between each of these personality
      domains and a history of childhood trauma. Australian adults (N = 116) were
      administered the Dissociative Experiences Scale, the Schizotypal Personality
      Questionnaire-Brief, and the Childhood Trauma Questionnaire. Hierarchical
      regression analysis revealed that both pathological and nonpathological
      dissociative tendencies were predicted by the dimensions of schizotypy, even
      after the contribution of childhood trauma had been removed. It is concluded that
      the relationship between dissociative tendencies and schizotypy is not an
      artifact of childhood abuse, but the clinical significance of this relationship
      remains to be established.

PMID- 11241365
TI  - Differential item functioning in a Spanish translation of the Beck Depression
      Inventory.
AB  - Brief and culturally compatible measures of depression are necessary, yet most
      depression scales are translated without regard for cultural biases. In this
      study, 292 medical outpatients completed an English or a Spanish-translated and
      back-translated version of the Beck Depression Inventory (BDI). The BDI items
      were analyzed for bias between Spanish and English-speaking patients to determine
      the equivalence of the scale. A Differential Item Function (DIF) using a Mantel
      Haenszel Approach for Ordered Response Categories was used to analyze how likely
      subjects in the two ethnic groups were to endorse each response category. The
      results suggest that regardless of level of depression, Latinos are more likely
      to endorse items reflecting tearfulness and punishment, and less likely to
      endorse inability to work. Cultural interpretations and recommendations for use
      of the BDI are discussed.

PMID- 11241366
TI  - MMPI-2 profiles of filicidal, mariticidal, and homicidal women.
AB  - The present study compared the Minnesota Multiphasic Personality Inventory-2
      (MMPI-2) clinical and content scale profiles of a group of adult women (N = 73)
      charged with either murder of their child (filicide) (n = 30), their partner
      (mariticide) (n = 19), or an unrelated adult (homicide) (n = 24). No significant
      differences were seen among the three groups on either the MMPI-2 clinical or
      content scales. Clinical inspection of the 53 valid MMPI-2 profiles (F < 110T)
      revealed a 6-8 mean profile for the filicidal women, a 2-6 mean profile for the
      mariticidal women, and a 4-8 mean profile for the homicidal women. Application of
      the data for criminal forensic psychological evaluations is discussed.

PMID- 11241368
TI  - Incidental recall on WAIS-R digit symbol discriminates Alzheimer's and
      Parkinson's diseases.
AB  - The purpose of this study was to examine how Alzheimer's (n = 37) and Parkinson's
      (n = 21) patients perform on the incidental recall adaptation to the Digit Symbol
      of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) and how such
      performance is related to established cognitive efficiency and memory measures.
      This adaptation requires the examinee to complete the entire subtest and then,
      without warning, to immediately recall the symbols associated with each number.
      Groups did not differ significantly on standard Digit Symbol administration (90
      seconds), but on recall Parkinson's patients recalled significantly more symbols
      and symbol-number pairs than Alzheimer's patients. Using only the number of
      symbols recalled, discriminate function analysis correctly classified 76% of
      these patients. Correlations between age-corrected scaled score, symbols
      incidentally recalled, and established measures of cognitive efficiency and
      memory provided evidence of convergent and divergent validity. Age-corrected
      scaled scores were more consistently and strongly related to cognitive
      efficiency, whereas symbols recalled were more consistently and strongly related
      to memory measures. These findings suggest that the Digit Symbol recall
      adaptation is actually assessing memory and that it can be another useful way to
      detect memory impairment.

PMID- 11241367
TI  - Reliability and factor structure of the Chinese version of the Self-report Family
      Inventory in Chinese adolescents.
AB  - The Chinese version (C-SFI) of the Self-Report Family Inventory (SFI) was
      administered to 3,649 Chinese adolescents. Results showed that the C-SFI is
      internally consistent. Factor analyses revealed that two factors were abstracted
      from the scale (positive family behavior and negative family behavior), and they
      could reliably be reproduced in different adolescent subsamples based on gender
      and grade. Contrary to the previous findings that there are five to six
      dimensions of the SFI, the present findings show that the C-SFI has two
      dimensions. This study suggests that clinical practitioners should be cautious in
      using the subscales in the SFI, particularly for the Chinese.

PMID- 11241369
TI  - Ethical behaviors of psychologists: changes since 1987.
AB  - Licensed psychologists (n = 92) in Illinois were surveyed regarding the frequency
      with which they engage in 82 behaviors of varying ethical appropriateness. For
      about one-third of the behaviors studied, results differed significantly from a
      similar national survey published in 1987, such that the current sample reported
      never engaging in the behavior more frequently than did the previous sample.
      These differences may be due to increased involvement of managed care in
      professional practice, the revised ethical code, or regional or sampling factors.
      Implications of these results, including the need to assess ethical norms
      frequently, are discussed.

PMID- 11241370
TI  - Pain patient profile and the assessment of malingered pain.
AB  - This study investigated whether a pain sample and pain simulators could be
      distinguished on the Pain Patient Profile (P3). Forty patients with a pain
      condition completed the P3 under normal instructions, while 20 students responded
      under instructions to feign a pain disorder but to attempt to avoid detection.
      The simulators did not differ on the P3 Validity Scale compared with the pain
      group, but scored significantly higher than the pain group on the P3 clinical
      scales (Depression, Anxiety, Somatization). The simulators were more likely to
      obtain an abnormal score (T score > 55) on all of the clinical scales. The
      Depression scale had highest positive and negative predictive power and correctly
      classified 80% of the participants. The P3 may be a useful screening tool for
      assessing those feigning pain but requires further research.

PMID- 11241372
TI  - Comparison of the Peabody Picture Vocabulary Test-Third Edition and Wechsler
      Adult Intelligence Scale-Third Edition with university students.
AB  - This study examined the relationship between the Peabody Picture Vocabulary Test
      Third Edition (PPVT-III) and Wechsler Adult Intelligence Scale-Third Edition
      (WAIS-III) using 40 adults who ranged in age from 18 to 41 (mean age of 22
      years). Participants were administered the PPVT-III and WAIS-III in
      counterbalanced fashion to control for order effects. Results revealed that the
      PPVT-III score was related to the WAIS-III Verbal IQ (VIQ) and Full Scale IQ
      (FSIQ) scores but unrelated to the Performance IQ (PIQ) score. In addition,
      analyses indicated that, while there were no significant differences between the
      PPVT-III score and WAIS-III mean FSIQ and PIQ scores, the PPVT-III mean score was
      significantly lower than the WAIS-III VIQ. Further analysis indicated that the
      PPVT-III adequately estimated WAIS-III FSIQ and VIQ scores for participants who
      were classified as Average or High Average on the WAIS-III. However, for
      participants in the Superior range, the PPVT-III tended to underestimate FSIQ and
      VIQ scores by approximately 10 points.

PMID- 11241371
TI  - A comparison of the short and long forms of the Multiple Affect Adjective Check
      List-Revised (MAACL-R).
AB  - Brief, reliable, and valid assessment instruments are very important for clinical
      psychology research and practice. The possible equivalency of a short form and
      the long form of the Multiple Affect Adjective Check List-Revised (MAACL-R;
      Zuckerman & Lubin,1985) was studied by correlating both forms of the MAACL-R with
      the State Trait Personality Inventory (Spielberger,1995); the Affect Balance
      Scale (Bradburn,1969); and the Sensation Seeking Scale (Zuckerman,1978).
      Reliability and validity of the two forms were equivalent.

PMID- 11241373
TI  - The Neuropsychological Impairment Scale-Senior: a procedure for evaluating
      awareness disturbance in geriatric patients.
AB  - The Neuropsychological Impairment Scale-Senior (NIS-S) is a 30-item, orally
      administered questionnaire for geriatric patients about symptoms of cognitive
      impairment, affective disturbance, and defensiveness. Clinical and nonclinical
      norms are described along with validity and reliability information. A procedure
      is presented for comparing a patient's self-reported cognitive impairment with
      scores on performance testing, which gauges whether the patient is over- or under
      reporting cognitive deficits.

PMID- 11241374
TI  - Characterization of CART neurons in the rat and human hypothalamus.
AB  - Cocaine- and amphetamine-regulated transcript (CART) is a recently described
      neuropeptide widely expressed in the rat brain. CART mRNA and peptides are found
      in hypothalamic sites such as the paraventricular nucleus (PVH), the supraoptic
      nucleus (SON), the lateral hypothalamic area (LHA), the dorsomedial nucleus of
      the hypothalamus (DMH), the arcuate nucleus (Arc), the periventricular nucleus
      (Pe), and the ventral premammillary nucleus (PMV). Intracerebroventricular
      administration of recombinant CART peptide decreases food intake and CART mRNA
      levels in the Arc are regulated by leptin. Leptin administration induces Fos
      expression in hypothalamic CART neurons in the PVH, the DMH, the Arc, and the
      PMV. In the current study, we used double label in situ hybridization
      histochemistry to investigate the potential direct action of leptin on
      hypothalamic CART neurons and to define the chemical identity of the hypothalamic
      CART neurons in the rat brain. We found that CART neurons in the Arc, DMH, and
      PMV express long form leptin-receptor mRNA, and the suppressor of cytokine
      signaling-3 (SOCS-3) mRNA after an acute dose of intravenous leptin. We also
      found that CART neurons in the parvicellular PVH, in the DMH and in the posterior
      Pe coexpress thyrotropin-releasing hormone (TRH) mRNA. CART neurons in the
      magnocellular PVH and in the SON coexpress dynorphin (DYN), and CART cell bodies
      in the LHA and in the posterior Pe coexpress melanin-concentrating hormone (MCH)
      and glutamic acid decarboxylase (GAD-67) mRNA. In the Arc, a few CART neurons
      coexpress neurotensin (NT) mRNA. In addition, we examined the distribution of
      CART immunoreactivity in the human hypothalamus. We found CART cell bodies in the
      PVH, in the SON, in the LHA, in the Arc (infundibular nucleus) and in the DMH. We
      also observed CART fibers throughout the hypothalamus, in the bed nucleus of the
      stria terminalis, and in the amygdala. Our results indicate that leptin directly
      acts on CART neurons in distinct nuclei of the rat hypothalamus. Furthermore,
      hypothalamic CART neurons coexpress neuropeptides involved in energy homeostasis,
      including MCH, TRH, DYN, and NT. The distribution of CART cell bodies and fibers
      in the human hypothalamus indicates that CART may also play a role in the
      regulation of energy homeostasis in humans.

PMID- 11241375
TI  - Differential expression of catecholamine biosynthetic enzymes in the rat
      ventrolateral medulla.
AB  - Adrenergic (C1) neurons located in the rostral ventrolateral medulla are
      considered a key component in the control of arterial blood pressure.
      Classically, C1 cells have been identified by their immunoreactivity for the
      catecholamine biosynthetic enzymes tyrosine hydroxylase (TH) and/or
      phenylethanolamine N-methyltransferase (PNMT). However, no studies have
      simultaneously demonstrated the expression of aromatic L-amino acid decarboxylase
      (AADC) and dopamine beta-hydroxylase (DBH) in these neurons. We examined the
      expression and colocalization of all four enzymes in the rat ventrolateral
      medulla using immunohistochemistry and reverse transcription-polymerase chain
      reaction (RT-PCR) analysis. Retrograde tracer injected into thoracic spinal
      segments T2-T4 was used to identify bulbospinal neurons. Using fluorescence and
      confocal microscopy, most cells of the C1 group were shown to be double or triple
      labeled with TH, DBH, and PNMT, whereas only 65-78% were immunoreactive for AADC.
      Cells that lacked detectable immunoreactivity for AADC were located in the
      rostral C1 region, and approximately 50% were spinally projecting. Some cells in
      this area lacked DBH immunoreactivity (6.5-8.3%) but were positive for TH and/or
      PNMT. Small numbers of cells were immunoreactive for only one of the four
      enzymes. Numerous fibres that were immunoreactive for DBH but not for TH or PNMT
      were noted in the rostral C1 region. Single-cell RT-PCR analysis conducted on
      spinally projecting C1 neurons indicated that only 76.5% of cells that contained
      mRNA for TH, DBH, and PNMT contained detectable message for AADC. These
      experiments suggest that a proportion of C1 cells may not express all of the
      enzymes necessary for adrenaline synthesis.

PMID- 11241376
TI  - Motor neurons rapidly accumulate DNA single-strand breaks after in vitro exposure
      to nitric oxide and peroxynitrite and in vivo axotomy.
AB  - The mechanisms of neuronal degeneration in motor neuron disease are not fully
      understood. We tested the hypothesis that oxidative stress in vitro and axotomy
      in vivo induce single-strand breaks (SSB) in DNA, a form of early DNA damage, in
      adult motor neurons early during their degeneration. We developed and
      characterized a novel cell suspension system enriched in motor neurons from adult
      rat spinal cord ventral horn. This cell system is approximately 84% neurons, with
      approximately 86% of these neurons being motor neurons; approximately 72% of
      these motor neurons are alpha-motor neurons. Motor neuron viability in suspension
      is approximately 100% immediately after isolation and approximately 61% after 12
      hours of incubation. During incubation, isolated motor neurons generate high
      levels of superoxide. We used single-cell gel electrophoresis (comet assay) to
      detect DNA-SSB in motor neurons. Exposure of motor neurons to nitric oxide (NO)
      donors (sodium nitroprusside or NONOate), H2O2, or NO donor plus H2O2 rapidly
      induces DNA-SSB and causes motor neuron degeneration, the occurrence of which is
      dose and time related, as represented by comet formation and cell loss. Motor
      neuron toxicity is potentiated by cotreatment with NO donor and H2O2 (at nontoxic
      concentrations alone). Peroxynitrite causes DNA-SSB in motor neurons. The DNA
      damage profiles (shown by the comet morphology and moment) of NO donors, NO donor
      plus H2O2, and peroxynitrite are similar. In an in vivo model of motor neuron
      apoptosis, DNA-SSB accumulate slowly in avulsed motor neurons before apoptotic
      nuclear features emerge, and the comet fingerprint is similar to NO toxicity. We
      conclude that motor neurons challenged by oxidative stress and axotomy accumulate
      DNA-SSB early in their degeneration and that the formation of peroxynitrite is
      involved in the mechanisms.

PMID- 11241378
TI  - Neural substrates for tongue-flicking behavior in snakes.
AB  - Snakes deliver odorants to the vomeronasal organ by means of tongue-flicks. The
      rate and pattern of tongue-flick behavior are altered depending on the chemical
      context. Accordingly, olfactory and vomeronasal information should reach motor
      centers that control the tongue musculature, namely, the hypoglossal nucleus
      (XIIN); however, virtually nothing is known about the circuits involved. In the
      present work, dextran amines were injected into the tongue of garter snakes
      (Thamnophis sirtalis) to identify the motoneurons of the XIIN. Tracers were then
      delivered into the XIIN to identify possible afferents of chemical information.
      Large injections into the XIIN yielded retrograde labeling in two chemosensory
      areas: the medial amygdala (MA) and the lateral posterior hypothalamic nucleus
      (LHN). Smaller injections only yielded labeled neurons in the LHN. In fact, the
      MA, which receives afferents from the accessory olfactory bulb, the rostroventral
      lateral cortex, and the nucleus sphericus, projects to the LHN. Injections into
      the MA did not show terminal labeling in the XIIN but in an area lateral to it.
      However, injections into the LHN gave rise not only to labeled fibers in the XIIN
      but also to retrograde labeling in the MA, thus confirming the chemosensory input
      to LHN. Injecting different fluorescent tracers into the tongue and into the LHN
      corroborated the projection from the LHN to the XIIN. The present report
      investigates further connections of the olfactory and vomeronasal systems and
      describes the afferent connections to XIIN in a nonmammalian vertebrate. The
      circuit for tongue-flicking behavior described herein should be evaluated using
      functional studies.

PMID- 11241379
TI  - Distribution of preproadrenomedullin mRNA in the rat central nervous system and
      its modulation by physiological stressors.
AB  - Adrenomedullin (ADM), encoded by the preproadrenomedullin (ppADM) gene, exerts
      multiple effects in a wide variety of peripheral and central tissues. Although
      ADM-like immunoreactivity has been shown to be widely distributed throughout the
      rat central nervous system (CNS), the detailed distribution of ppADM gene
      expression in the CNS and its modulation by physiological stimuli remain unknown.
      In our study, in situ hybridization was used to localize ppADM mRNA in the rat
      brain and to quantify its levels after exposure to different stressors including
      lipopolysaccharide (LPS; 100 microg/kg, iv), restraint stress (2 cycles of 1 hour
      restraint/1 hour rest), and 24 hours of dehydration. In addition, Fos
      immunoreactivity was used to identify the activation of neurons in response to
      LPS. Our results show that ppADM mRNA is widely distributed throughout the rat
      CNS, with especially high levels in autonomic centers including the hypothalamic
      paraventricular nucleus (PVN), hypothalamic supraoptic nucleus (SON), locus
      coeruleus, ventrolateral medulla, and intermediolateral cell column of the spinal
      cord. Furthermore, LPS inhibits ppADM gene expression in the parvocellular PVN
      (pPVN), magnocellular PVN (mPVN), SON, dorsal motor nucleus of the vagus, and
      area postrema among examined regions; restraint stress reduces ppADM mRNA levels
      in the pPVN, mPVN, SON, nucleus of the solitary tract, dorsal motor nucleus of
      the vagus, area postrema, and subfornical organ; 24 hours of water deprivation
      decreases ppADM gene expression only in the mPVN and SON. Taken together, our
      results suggest that ADM is involved in the regulation of the hypothalamo
      neurohypophysial system, the hypothalamo-pituitary-adrenal axis, and central
      autonomic functions.

PMID- 11241377
TI  - Sexual dimorphism and developmental expression of signal-transduction machinery
      in the vomeronasal organ.
AB  - We have explored the use of a new model to study the transduction of chemosignals
      in the vomeronasal organ (VNO), for which the functional pathway for chemical
      communication is incompletely understood. Because putative vomeronasal receptors
      in mammalian and other vertebrate models belong to the superfamily of G-protein
      coupled receptors, the objective of the present study was to define which G
      protein subunits were present in the VNO of Sternotherus odoratus (stinkpot or
      musk turtle) in order to provide directionality for future functional studies of
      the downstream signaling cascades. The turtle vomeronasal epithelium (VNE) was
      found to contain the G-proteins G(beta) and G(alphail-3) at the microvillar
      layer, the presumed site of signal tranduction in these neurons, as evidenced by
      immunocytochemical techniques. G(alphao) labeled the axon bundles in the VNE and
      the somata of the vomeronasal sensory neurons but not the microvillar layer.
      Densitometric analysis of Western blots indicated that the VNO from females
      contained greater concentrations of G(alphai1-3) compared with males. Sexually
      immature (juvenile) turtles showed intense immunolabeling for all three subunits
      (G(beta), G(alphai1-3), and G(alphao)) in the axon bundles and an absence of
      labeling in the microvillar layer. Another putative signaling component found in
      the microvilli of mammalian VNO, transient receptor potential channel, was also
      immunoreactive in S. odoratus in a gender-specific manner, as quantified by
      Western blot analysis. These data demonstrate the utility of Sternotherus for
      discerning the functional signal transduction machinery in the VNO and may
      suggest that gender and developmental differences in effector proteins or
      cellular signaling components may be used to activate sex-specific behaviors.

PMID- 11241380
TI  - Uncrossed and crossed projections from the upper cervical spinal cord to the
      cerebellar nuclei in the rat, studied by anterograde axonal tracing.
AB  - In the upper cervical spinal segments, neurons in the medial part of lamina VI
      give rise to uncrossed spinocerebellar axons, whereas the central cervical
      nucleus (CCN) and neurons in laminae VII and VIII give rise to crossed
      spinocerebellar axons. Using anterograde labeling with biotinylated dextran in
      the rat, we examined the projections of these neuronal groups to the cerebellar
      nuclei. Uncrossed and crossed projections were distinguished by cerebellar
      lesions placed on the side contralateral or ipsilateral to the tracer injections
      confined to the second and third cervical spinal segments (C2 and C3,
      respectively). Labeled terminals of uncrossed projections were seen in the
      middle, dorsal, and ventrolateral parts of the middle subdivision and in the
      ventral part of the caudomedial subdivision of the medial nucleus. In the
      anterior interpositus nucleus, terminals were seen in the middle of the
      mediolateral extent, whereas, in the posterior interpositus nucleus, they were
      seen in lateral and caudal parts. The terminals of crossed projections from the
      CCN were distributed ventrally in medial to ventrolateral parts of the middle
      subdivision of the medial nucleus. Some terminals were seen in the caudomedial
      subdivision of the medial nucleus. In the anterior interpositus nucleus, labeled
      terminals were seen mainly in rostromedial parts, whereas, in the posterior
      interpositus nucleus, they were seen in caudal and dorsal parts of the medial
      half. The present study suggests that the medial lamina VI group and the CCN in
      the upper cervical segments project to the different areas of the cerebellar
      nuclei and are concerned with different functions.

PMID- 11241381
TI  - Dopamine transporter immunoreactivity in monkey cerebral cortex: regional,
      laminar, and ultrastructural localization.
AB  - Dopamine (DA) influences a number of cognitive and motor functions that are
      mediated by the primate cerebral cortex, and the DA membrane transporter (DAT) is
      known to be a critical regulator of DA neurotransmission in subcortical
      structures in rodents. To gain insight into the possible functional role of
      cortical DAT, we compared the regional, laminar, and ultrastructural distribution
      of DAT immunoreactivity to that of tyrosine hydroxylase (TH), the rate-limiting
      enzyme in DA synthesis, in the cerebral cortex of macaque monkeys. DAT
      immunoreactive (DAT-IR) axons were present throughout the cortical mantle, with
      substantial differences in density and laminar distribution across
      cytoarchitectonic areas. In particular, high densities of DAT-IR axons were
      present in certain regions (e.g., posterior parietal cortex, dentate gyrus) not
      previously thought to receive a substantial DA input. The laminar distribution of
      DAT-IR axons ranged from a restricted localization of labeled axons to layer 1 in
      lightly innervated regions to the presence of axons in all six cortical layers,
      with a particularly dense plexus in deep layer 3, in highly innervated regions.
      These regional and laminar patterns paralleled those of TH-IR axons, but several
      differences in fiber morphology and ultrastructural localization of DAT were
      observed. For example, in contrast to TH, DAT immunoreactivity in the cortex was
      localized predominantly to small-diameter profiles, whereas, in the dorsolateral
      caudate nucleus, DAT and TH immunoreactivities were present in both large
      diameter and small-diameter profiles, which may represent varicose and
      intervaricose axon segments, respectively. Overall, the distribution of DAT-IR
      axons confirms and extends the results of previous reports, using other markers
      of DA axons, that the DA innervation of the primate cerebral cortex is global but
      specialized on both a regional basis and a laminar basis. In particular, these
      observations reveal an anatomical substrate for a direct and potent influence of
      DA over neuronal activity in posterior parietal cortex and in certain regions of
      the temporal lobe. However, due to its predominant distribution to small-diameter
      profiles, immunoreactivity for DAT may not be an appropriate ultrastructural
      marker for larger DA varicosities in the primate cortex. Moreover, this
      distribution of DAT suggests that cortical DA fibers may permit greater
      neurotransmitter diffusion than subcortical DA axons.

PMID- 11241382
TI  - Excitatory synaptic inputs on myenteric Dogiel type II neurones of the pig ileum.
AB  - The synaptic input on myenteric Dogiel type II neurones (n = 63) obtained from
      the ileum of 17 pigs was studied by intracellular recording. In 77% of the
      neurones, electrical stimulation of a fibre tract evoked fast excitatory
      postsynaptic potentials (fEPSPs) with an amplitude of 6 +/- 5 mV (mean +/- S.D.)
      and lasting 49 +/- 29 ms. The nicotinic nature of the fEPSPs was demonstrated by
      superfusing hexamethonium (20 microM). High-frequency stimulation (up to 20 Hz, 3
      seconds) did not result in a rundown of the fEPSPs, and did not evoke slow
      excitatory or inhibitory postsynaptic potentials. The effects of
      neurotransmitters, possibly involved in these excitatory responses, were
      investigated. Pressure microejection of acetylcholine (10 mM in pipette) resulted
      in a fast nicotinic depolarisation in 67%(18/27) of the neurones (13 +/- 9 mV,
      duration 7.0 +/- 7.2 seconds) as did 1,1-dimethyl-4-phenylpiperazinium iodide
      (DMPP) application (10 mM; 14 +/- 10 mV, duration 4.1 +/- 2.8 seconds) in 76% of
      the cells. The fast nicotinic response to acetylcholine was sometimes (6/27)
      followed by a slow muscarinic depolarisation (8 +/- 4 mV; duration 38.7 +/- 10.8
      seconds). Immunostaining revealed 5-hydroxytryptamine hydrochloride (5-HT)- and
      calcitonin gene-related peptide (CGRP)-positive neuronal baskets distributed
      around and in close vicinity to Dogiel type II neuronal cell bodies.
      Microejection of 5-HT (10 mM) resulted in a fast nicotinic-like depolarisation
      (12 +/- 6 mV, duration 3.0 +/- 1.3 seconds) in 4 of 8 neurones tested, whereas
      microejection of CGRP (20 mM) gave rise to a slow muscarinic-like depolarisation
      (6 +/- 2 mV, duration 56.0 +/- 27.5 seconds) in 8 of 12 neurones tested. In
      conclusion, myenteric Dogiel type II neurones in the porcine ileum receive
      diverse synaptic input. Mainly with regard to the prominent presence of nicotinic
      responses, these neurones behave contrary to their guinea pig counterparts.

PMID- 11241383
TI  - Glial cell line-derived neurotrophic factor-responsive and neurotrophin-3
      responsive neurons require the cytoskeletal linker protein dystonin for postnatal
      survival.
AB  - We have investigated the fate of different neurotrophin-responsive subpopulations
      of dorsal root ganglion neurons in dystonia musculorum (dt) mice. These mice have
      a null mutation in the cytoskeletal linker protein, dystonin. Dystonin is
      expressed by all sensory neurons and cross links actin filaments, intermediate
      filaments, and microtubules. The dt mice undergo massive sensory
      neurodegeneration postnatally and die at around 4 weeks of age. We assessed the
      surviving and degenerating neuronal populations by comparing the dorsal root
      ganglion (DRG) neurons and central and peripheral projections in dt mice and
      wildtype mice. Large, neurofilament-H-positive neurons, many of which are muscle
      afferents and are neurotrophin-3 (NT-3)-responsive, were severely decreased in
      number in dt DRGs. The loss of muscle afferents was correlated with a
      degeneration of muscle spindles in skeletal muscle. Nerve growth factor (NGF)
      responsive populations, which were visualized using calcitonin gene-related
      peptide and p75, appeared qualitatively normal in the lumbar spinal cord, DRG,
      and hindlimb skin. In contrast, glial cell line-derived neurotrophic factor
      (GDNF)-responsive populations, which were visualized using the isolectin B-4 and
      thiamine monophosphatase, were severely diminished in the lumbar spinal cord,
      DRG, and hindlimb skin. Analysis of NT-3, NGF, and GDNF mRNA levels using
      semiquantitative reverse transcriptase-polymerase chain reaction revealed normal
      trophin synthesis in the peripheral targets of dt mice, arguing against decreased
      trophic synthesis as a possible cause of neuronal degeneration. Thus, the absence
      of dystonin results in the selective survival of NGF-responsive neurons and the
      postnatal degeneration of many NT-3- and GDNF-responsive neurons. Our results
      reveal that the loss of this ubiquitously expressed cytoskeletal linker has
      diverse effects on sensory subpopulations. Moreover, we show that dystonin is
      critical for the maintenance of certain DRG neurons, and its function may be
      related to neurotrophic support.

PMID- 11241384
TI  - Organization of cerebellar and area "y" projections to the nucleus reticularis
      tegmenti pontis in macaque monkeys.
AB  - Axonal projections to the nucleus reticularis tegmenti pontis (RTP) were studied
      in 11 macaque monkeys by mapping axonal degeneration from lesions centered in the
      dentate and interpositus anterior (IA) nuclei and by mapping anterograde
      transport of tritiated amino acid precursors injected into the dentate nucleus.
      Projections from the dentate and IA nuclei overlap in central parts of the body
      of RTP, but the terminal field of dentate axons extends dorsomedial and rostral
      to the terminal field of IA axons, and IA terminal fields extend more
      ventrolaterally. A caudal to rostral topography of projections from each nucleus
      onto dorsal to ventral parts of RTP was seen. Projections from rostral parts of
      both nuclei terminate in a sublemniscal part of the nucleus. The topography of
      dentate and IA projections onto central to ventrolateral RTP appears to match
      somatotopic maps of these cerebellar nuclei with the somatotopic map of
      projections to RTP from primary motor cortex. Projections from caudal and ventral
      parts of the dentate nucleus appear to overlap oculomotor inputs to rostral,
      dorsal, and medial RTP from the frontal and supplementary eye fields, the
      superior colliculus, and the oculomotor region of the caudal fastigial nucleus.
      Projections to the paramedian part of RTP from vestibular area "y" were also
      found in two cases that correlated with projections to vertical oculomotor
      motoneurons. The maps of dentate and IA projections onto RTP correlate
      predictably with maps of dentate and IA projections to the ventrolateral thalamus
      and subnuclei of the red nucleus that were made from these same cases (Stanton
      [1980b] J. Comp. Neurol. 192:377-385).

PMID- 11241385
TI  - Parkin immunoreactivity in the brain of human and non-human primates: an
      immunohistochemical analysis in normal conditions and in Parkinsonian syndromes.
AB  - The etiology of Parkinson's disease is unknown, but the gene involved in an
      autosomic recessive form of the disease with early onset has recently been
      identified. It codes for a protein with an unknown function called parkin. In the
      present study we produced a specific polyclonal antiserum against human parkin.
      Immunohistochemical analysis showed that parkin is expressed in neuronal
      perikarya and processes but also in glial and blood vessels in the primate brain
      (human and monkey). Electron microscopy indicated that parkin immunoreactivity is
      mostly located in large cytoplasmic vesicles and at the level of the endoplasmic
      reticulum. Parkin was expressed heterogeneously in various structures of the
      brain. It was detectable in the dopaminergic systems at the level of the
      perikarya in the mesencephalon but also in the striatum. However, parkin was also
      expressed by numerous nondopaminergic neurons. The staining intensity of parkin
      was particularly high in the hippocampal formation, the pallidal complex, the red
      nucleus, and the cerebellum. Comparison of control subjects with patients with
      Parkinson's disease and control animals with 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP)-intoxicated animals revealed a loss of parkin
      immunoreactive neurons only in the substantia nigra pars compacta. Furthermore,
      the surviving dopaminergic neurons in the parkinsonian state continued to express
      parkin at a level similar to that observed in the control situation. These data
      indicate that parkin is a widely expressed protein. Thus, the degeneration of
      dopaminergic neurons in familial cases of Parkinson's disease with autosomal
      recessive transmission cannot be explained solely in terms of an alteration of
      this protein.

PMID- 11241386
TI  - Immunotoxic destruction of distinct catecholamine subgroups produces selective
      impairment of glucoregulatory responses and neuronal activation.
AB  - The toxin-antibody complex anti-d(beta)h-saporin (DSAP) selectively destroys
      d(beta)h-containing catecholamine neurons. To test the role of specific
      catecholamine neurons in glucoregulatory feeding and adrenal medullary secretion,
      we injected DSAP, unconjugated saporin (SAP), or saline bilaterally into the
      paraventricular nucleus of the hypothalamus (PVH) or spinal cord (T2-T4) and
      subsequently tested rats for 2-deoxy-D-glucose (2DG)-induced feeding and blood
      glucose responses. Injections of DSAP into the PVH abolished 2DG-induced feeding,
      but not hyperglycemia. 2DG-induced Fos expression was profoundly reduced or
      abolished in the PVH, but not in the adrenal medulla. The PVH DSAP injections
      caused a nearly complete loss of tyrosine hydroxylase immunoreactive (TH-ir)
      neurons in the area of A1/C1 overlap and severe reduction of A2, C2, C3
      (primarily the periventricular portion), and A6 cell groups. Spinal cord DSAP
      blocked 2DG-induced hyperglycemia but not feeding. 2DG-induced Fos-ir was
      abolished in the adrenal medulla but not in the PVH. Spinal cord DSAP caused a
      nearly complete loss of TH-ir in cell groups A5, A7, subcoeruleus, and
      retrofacial C1 and a partial destruction of C3 (primarily the ventral portion)
      and A6. Saline and SAP control injections did not cause deficits in 2DG-induced
      feeding, hyperglycemia, or Fos expression and did not damage catecholamine
      neurons. DSAP eliminated d(beta)h immunoreactivity but did not cause significant
      nonspecific damage at injection sites. The results demonstrate that hindbrain
      catecholamine neurons are essential components of the circuitry for glucoprivic
      control of feeding and adrenal medullary secretion and indicate that these
      responses are mediated by different subpopulations of catecholamine neurons.

PMID- 11241387
TI  - Comparison of unilateral and bilateral intrastriatal 6-hydroxydopamine-induced
      axon terminal lesions: evidence for interhemispheric functional coupling of the
      two nigrostriatal pathways.
AB  - Partial lesions of the nigrostriatal dopamine system can be induced reliably by
      the intrastriatal injection of 6-hydroxydopamine (6-OHDA) and are considered to
      be analogous to the early stages of human Parkinson's disease. Previous studies
      have established a clear correlation between different doses and placements of
      the 6-OHDA toxin and the degree of neurodegenerative changes and behavioral
      impairments. In the present study, the influence of the interdependence between
      the two nigrostriatal systems in both hemispheres on the effects on sensorimotor
      behavioral performances after terminal 6-OHDA lesions was investigated. The
      behavioral effects were correlated to the extent of nigral dopamine neuron cell
      and striatal tyrosine-hydroxylase (TH)-positive fiber loss. Sprague-Dawley rats
      receiving unilateral intrastriatal 6-OHDA injections (4 x 5 microg) exhibited a
      30-70% reduction in striatal TH-positive fiber density along an anterior
      posterior gradient, an 80% loss of nigral dopamine neurons and a mild degree of
      behavioral impairments as revealed by amphetamine-induced rotational asymmetry,
      and a reduced performance in the stepping and postural balance tests. When the
      same amount of toxin was injected twice into both hemispheres (2 x 4 x 5 microg),
      additional behavioral deficits were observed, consisting of a significant, but
      temporary, weight loss, a stable reduction in general locomotor activity and
      explorational behavior, and a long-term deficit in skilled forelimb use. This is
      interesting in light of the morphological findings, in which uni- and bilaterally
      lesioned animals did not differ significantly in the extent of TH-immunoreactive
      fiber and dopamine neuron loss within the nigrostriatal system in each lesioned
      hemisphere. These results indicate that the interdependent regulation of the two
      nigrostriatal systems may provide some compensatory support for the function and
      behavioral performance of the lesioned side via the normal unlesioned side, which
      is lost in animals with bilateral lesions of the nigrostriatal system. Therefore,
      this model of uni- and bilateral partial lesions of the nigrostriatal system, as
      characterized in the present study, may foster further exploration of
      compensatory functional mechanisms active in the early stages of Parkinson's
      disease and promote development of novel neuroprotective and restorative
      strategies.

PMID- 11241388
TI  - Hippocampal dependent learning ability correlates with N-methyl-D-aspartate
      (NMDA) receptor levels in CA3 neurons of young and aged rats.
AB  - Hippocampal N-methyl-D-Aspartate (NMDA) receptors mediate mechanisms of cellular
      plasticity critical for spatial learning in rats. The present study examined the
      relationship between spatial learning and NMDA receptor expression in discrete
      neuronal populations, as well as the degree to which putative age-related changes
      in NMDA receptors are coupled to the effects of normal aging on spatial learning.
      Young and aged Long-Evans rats were tested in a Morris water maze task that
      depends on the integrity of the hippocampus. Levels of NR1, the obligatory
      subunit for a functional NMDA receptor, were subsequently quantified both
      biochemically by Western blot in whole homogenized hippocampus, and
      immunocytochemically by using a high-resolution confocal laser scanning
      microscopy method. The latter approach allowed comprehensive, regional analysis
      of discrete elements of excitatory hippocampal circuitry. Neither method revealed
      global changes, nor were there region-specific differences in hippocampal NR1
      levels between young and aged animals. However, across all subjects, individual
      differences in spatial learning ability correlated with NR1 immunofluorescence
      levels selectively in CA3 neurons of the hippocampus. Parallel confocal
      microscopic analysis of the GluR2 subunit of the alpha-amino-3-hydroxy-5-methyl-4
      isoxazole proprionic acid (AMPA) receptor failed to reveal reliable differences
      as a function of age or spatial learning ability. This analysis linking age,
      performance, and NR1 levels demonstrates that although dendritic NR1 is generally
      preserved in the aged rat hippocampus, levels of this receptor subunit in
      selective elements of hippocampal circuitry are linked to spatial learning. These
      findings suggest that NMDA receptor abundance in CA3 bears a critical
      relationship to learning mediated by the hippocampus throughout the life span.

PMID- 11241389
TI  - Postnatal regulation of limb proprioception by muscle-derived neurotrophin-3.
AB  - To investigate the effects of neurotrophin-3 (NT-3) on postnatal proprioceptive
      neurons and their targets, transgenic mice were generated that use the myosin
      light chain 1 (mlc) promoter to overexpress NT-3 in skeletal muscle. Ribonuclease
      protection assays revealed that NT-3 overexpression in hindlimb skeletal muscle
      began at embryonic day 14 (E14) and continued throughout adulthood.
      Overexpression of NT-3 during late embryogenesis resulted in increased numbers of
      large sensory and small fusimotor axons. Within a week of birth, mlc/NT-3 mice
      retract their limbs to the torso when lifted by the tail. Footprint analysis
      revealed that mlc/NT-3 mice had significant abnormalities in their gait compared
      with wild-types. Beam walking and rotorod analysis confirmed the poor limb
      control by mlc/NT-3 mice. These locomotive deficits progressively worsened with
      age and were likely related to the formation of morphologically abnormal muscle
      spindles. The most common spindle anomaly was the presence of excessive
      intrafusal bag fibers within individual muscle spindles. To assess the role of NT
      3 in recovery from nerve injury, sciatic nerve crushes were performed in young
      adult mice. Two days after injury, mlc/NT-3 mice displayed significantly improved
      sciatic functional indexes and a significant increase in muscle spindles that
      remained associated with axons. The latter finding suggests that excess NT-3 in
      muscle may retard the degeneration of proprioceptive axons after nerve crush.
      Long-term survival after nerve injury in mlc/NT-3 mice did not induce further
      changes in spindle number or morphology. These findings demonstrate that, in
      addition to promoting embryonic proprioceptive neuron survival, postnatal
      overexpression of NT-3 in muscle leads to abnormal spindle formation and deficits
      in locomotive control. However, our results also show that NT-3 may be
      therapeutic for proprioceptive axons immediately after nerve injury by delaying
      axon degeneration.

PMID- 11241390
TI  - Gonadal steroids reduce the density of axospinous synapses in the developing rat
      arcuate nucleus: an electron microscopy analysis.
AB  - The developing brain is exquisitely sensitive to gonadal steroid hormones, which
      permanently differentiate the neural substrate during a critical developmental
      period. One of the more striking sexual dimorphisms in the adult rat brain is
      synaptic patterning in the arcuate nucleus (ARC); females have twice the number
      of axospinous synapses as males (Matsumoto and Arai [1980] Brain Res. 190:238
      242). Previously, we have demonstrated that a similar dimorphism in spine
      densities on ARC dendrites is present as early as early as postnatal day 2 (PN2)
      in Golgi-impregnated rat brains (Mong et al. [1999] J. Neurosci. 19:1464-1472).
      Males have 37% fewer dendritic spines than females. Moreover, these spine
      densities are sensitive to changes in the hormonal milieu such that males
      castrated on the day of birth have a significant increase in spine density,
      whereas females masculinized at birth by gonadal steroid exposure have a
      decreased dendritic spine density. One of the limitations of the Golgi technique
      is the inability to confirm the presence of synapses. The current study used
      quantitative electron microscopy and demonstrated that testosterone exposure
      dramatically reduced axospinous synapses in the ARC by PN 2. Males had 54% fewer
      and masculinized females had 77% fewer axospinous synapses than females (P < 0.05
      and P < 0.01, respectively). We previously reported that gonadal steroids induce
      coincident changes in neuronal and astrocyte morphology in the neonatal ARC (Mong
      et al., 1999), and here confirm that these changes include an altered synaptic
      pattern that is strikingly similar to that observed in the adult (Matsumoto and
      Arai, 1980).

PMID- 11241392
TI  - Cl(-)-ATPases: Novel primary active transporters in biology.
AB  - Five widely documented mechanisms of chloride transport across plasma membranes
      are anion-coupled antiport, sodium and hydrogen-coupled symport, Cl(-)channels,
      and an electrochemical coupling process. No genetic evidence has yet been
      provided for primary active chloride transport despite numerous reports of
      cellular Cl(-)-stimulated ATPases co-existing, in the same tissue, with uphill
      chloride transport that could not be accounted for by the five common chloride
      transport processes. Cl(-)-stimulated ATPase activity is a common property of
      practically all biological cells with the major location being of mitochondrial
      origin. It also appears that plasma membranes are sites of Cl(-)-stimulated
      ATPase activity. Recent studies of Cl(-)-stimulated ATPase activity and active
      chloride transport in the same membrane system, including liposomes, suggest a
      medication by the ATPase in net movement of chloride up its electrochemical
      gradient across plasma membranes. Further studies, especially from a molecular
      biological perspective, are required to confirm a direct transport role to plasma
      membrane-localized Cl(-)-stimulated ATPases. J. Exp. Zool. 289:215-223, 2001.

PMID- 11241393
TI  - Cl(-)-ATPase in rat brain and kidney.
AB  - Cl(-)-stimulated ATPase/ATP-dependent Cl(-) pump (Cl(-)-ATPase/pump) has been
      found as a candidate for an active outwardly directed Cl(-) transporter in brain
      neurons. (1) A 520-kDa protein complex with Cl(-)-ATPase/pump activity was
      isolated from rat brain. It consisted of four protein subunits (51, 55, 60, and
      62 kDa proteins), the 51-kDa protein being a covalent phosphorylenzyme subunit.
      (2) An antiserum against the 51-kDa protein inhibited Cl(-)-ATPase/pump activity.
      Western blot analysis showed an immunoreactive 51-kDa protein in the brain,
      spinal cord, and kidney. By enzyme histochemistry and immunohistochemistry, Cl(-)
      ATPase-like activity or immunoreactivity was observed on the plasma membranes of
      brain neurons, and on the baso-lateral membranes of type A intercalated cells of
      renal collecting ducts. (3) Reconstituted Cl(-)-ATPase/pump activity was highest
      in liposomes with phosphatidylinositol-4-monophosphate. LiCl, an inhibitor of
      inositolphosphatase, reduced Cl(-)-ATPase activity and increased intracellular
      Cl(-) concentrations in cultured rat hippocampal neurons with increased
      phosphatidylinositol turnover. (4) In the brains of patients with Alzheimer's
      disease (AD), where phosphatidylinositol 4-kinase activity is reduced, Cl(-)
      ATPase activity was also reduced. Thus, Cl(-)-ATPase is likely an outwardly
      directed ATP-dependent Cl(-) transporter that consists of four subunits and is
      regulated by phosphatidylinositol-4-monophosphate. Changes in Cl(-)-ATPase
      activity may be related to the pathophysiology of human neurodegenerative
      diseases. J. Exp. Zool. 289:224-231, 2001.

PMID- 11241394
TI  - Biology of the 2Na+/1H+ antiporter in invertebrates.
AB  - The functional expression of membrane transport proteins that are responsible for
      exchanging sodium and protons is a ubiquitous phenomenon. Among vertebrates the
      Na+/H+ antiporter occurs in plasma membranes of polarized epithelial cells and
      non-polarized cells such as red blood cells, muscle cells, and neurons, and in
      each cell type the transporter exchanges one sodium for one hydrogen ion, is
      inhibited by amiloride, and regulates intracellular pH and sodium concentration
      within tight limitations. In polarized epithelial cells this transporter occurs
      in two isoforms, each of which is restricted to either the brush border or
      basolateral cell membrane, and perform somewhat different tasks in the two
      locations. In prokaryotic cells, sodium/proton exchange occurs by an electrogenic
      1Na+/2H+ antiporter that is coupled to a primary active proton pump and together
      these two proteins are capable of tightly regulating the intracellular
      concentrations of these cations in cells that may occur in environments of 4 M
      NaCl or pH 10-12. Invertebrate epithelial cells from the gills, gut, and kidney
      also exhibit electrogenic sodium/proton exchange, but in this instance the
      transport stoichiometry is 2Na+/1H+. As with vertebrate electroneutral Na+/H+
      exchange, the invertebrate transporter is inhibited by amiloride, but because of
      the occurrence of two external monovalent cation binding sites, divalent cations
      are able to replace external sodium and also be transported by this system. As a
      result, both calcium and divalent heavy metals, such as zinc and cadmium, are
      transported across epithelial brush border membranes in these animals and
      subsequently undergo a variety of biological activities once accumulated within
      these cells. Absorbed epithelial calcium in the crustacean hepatopancreas may
      participate in organismic calcium balance during the molt cycle and accumulated
      heavy metals may undergo complexation reactions with intracellular anions as a
      detoxification mechanism. Therefore, while the basic process of sodium/proton
      exchange may occur in invertebrate cells, the presence of the electrogenic
      2Na+/1H+ antiporter in these cells allows them to perform a wide array of
      functions without the need to develop and express additional specialized
      transport proteins. J. Exp. Zool. 289:232-244, 2001.

PMID- 11241395
TI  - Sulfate transport mechanisms in epithelial systems.
AB  - A novel invertebrate gastrointestinal transport mechanism has been shown to
      couple chloride-sulfate exchange in an electrogenic fashion. In the lobster,
      Homarus americanus, the hepatopancreas, or digestive gland, exists as an
      outpocketing of the digestive tract, representing a single cell layer separating
      the gut lumen and an open circulatory system composed of hemolymph.
      Investigations utilizing independently prepared brush border and basolateral
      membrane vesicles revealed discrete antiport systems which possess the capacity
      to bring about a transcellular secretion of sulfate. The luminal antiport system
      functions as a high-affinity, one-to-one chloride-sulfate exchanger that is
      stimulated by an increase in luminal hydrogen ion concentration. Such a system
      would take advantage of the high chloride concentration of ingested seawater as
      well as the high proton concentrations generated during digestion, which further
      suggests a potential regulation by resident sodium-proton exchangers. Exchange of
      one chloride for one divalent sulfate ion provides the driving force for
      electrogenic vectorial translocation. The basolateral antiport system was found
      to be electroneutral in nature, responsive to gradients of the dicarboxylic anion
      oxalate while lacking in proton stimulation. No evidence of sodium-sulfate co
      transport, commonly reported for the brush border of vertebrate renal and
      intestinal epithelia, was observed in either membrane preparation. The two
      antiporters together can account for the low hemolymph to seawater sulfate levels
      previously described in decapod crustaceans. A secretory pathway for sulfate
      based upon electrogenic chloride-antiport may appear among invertebrates partly
      in response to digestion taking place in a seawater environment. J. Exp. Zool.
      289:245-253, 2001.

PMID- 11241396
TI  - Transport of exogenous organic substances by invertebrate integuments: the field
      revisited.
AB  - The notion that some marine invertebrates can use integumental uptake of organic
      compounds as a nutritional supplement dates back to the late 19th and early 20th
      centuries. This article provides a brief overview of more than a century's
      research, as it relates to significant stages in the development of experimental
      methods and concepts of general physiology. Emphasis is placed on changing
      paradigms and on the interplay between this specialized field of investigation
      and the mainstream of physiological thought. The present status of the field is
      summarized. The general consensus is challenged on the basis of previously
      published and new data from the author's laboratory. Particular emphasis is
      placed on data pointing toward an ultra-rapid turnover of amino acids in part of
      the epidermal space of the polychaete worm Nereis diversicolor. It is suggested
      that intra-epidermal L-alanine is compartmentalized metabolically or physically,
      and the consequences of this proposition are discussed in view of the general
      concepts of secondary active transport and intracellular isosmotic regulation.
      Future studies in this area of comparative physiology should concentrate not only
      on the molecular characteristics of the transporter proteins, but also on the way
      their function is integrated in the cellular physiology of the transporting
      cells. J. Exp. Zool. 289:254-265, 2001.

PMID- 11241397
TI  - Acclimation to hypoxia increases survival time of zebrafish, Danio rerio, during
      lethal hypoxia.
AB  - Survivorship of zebrafish, Danio rerio, was measured during lethal hypoxic stress
      after pretreatment in water at either ambient oxygen or at a lowered, but
      nonlethal, level of oxygen. Acclimation to nonlethal hypoxia (pO(2) congruent
      with 15 Torr; ca. 10% air-saturation) for 48 hr significantly extended survival
      time during more severe hypoxia (pO(2) congruent with 8 Torr; ca. 5% air
      saturation) compared to survival of individuals with no prior hypoxic exposure.
      The magnitude of the acclimation effect depended upon the sex of the fish:
      hypoxia pretreatment increased the survival times of males by a factor of
      approximately 9 and that of females by a factor of 3 relative to controls. In
      addition, survival time of control and hypoxia acclimated fish depended upon when
      in the year experiments were conducted. Survival times were 2-3 times longer when
      measured in the late fall or winter compared to survival times measured during
      the spring or summer. These results demonstrate a direct survival benefit of
      short-term acclimation to hypoxia in this genetically tractable fish. The fact
      that the acclimation effect depended upon the sex of the fish and the season
      during which experiments were conducted demonstrates that other genetic and/or
      environmental factors affect hypoxia tolerance in this species. J. Exp. Zool.
      289:266-272, 2001.

PMID- 11241398
TI  - Vasoactivity of the ventral aorta of the American eel (Anguilla rostrata),
      Atlantic hagfish ( Myxine glutinosa), and sea lamprey (Petromyzon marinus).
AB  - To determine if vascular smooth muscle from teleost and agnathan fishes expresses
      receptors for signaling agents that are important in vascular tension in other
      vertebrates, we exposed rings of aortic vascular smooth muscle from the eel
      (Anguilla rostrata), the hagfish (Myxine glutinosa), and the lamprey (Petromyzon
      marinus) to a suite of putative agonists, including: acetylcholine, endothelin,
      nitric oxide, natriuretic peptides, and prostanoids. Acetylcholine constricted
      aortic rings from the eel, but had no effect on the rings from lamprey. On the
      other hand, endothelin constricted rings from all three species. Use of receptor
      specific ET agonists demonstrated that only ET(A) receptors are expressed in the
      eel and lamprey aorta. The nitric oxide donor sodium nitroprusside or nitric
      oxide itself dilated rings from the eel, but both agonists constricted rings from
      the hagfish and NO produced a biphasic response (constriction followed by
      dilation) in the lamprey. Two natriuretic peptides, eel ANP and porcine CNP,
      produced marginally significant dilation in the eel aorta, human ANP dilated the
      hagfish rings, and pCNP and eANP dilated the lamprey rings. The prostanoids
      PGE(1) and PGE(2) both dilated the eel aortic rings, and PGE(1) and
      carbaprostacyclin (stable PGI(2) agonist) dilated the hagfish and lamprey rings.
      Our results suggest that receptors for a variety of vasoactive signaling agents
      are expressed in the aortic smooth muscle of the earliest vertebrates (lamprey
      and hagfish), as well as the more advanced teleosts (eel).

PMID- 11241399
TI  - Sex differences in plasma corticosterone in desert tortoises, Gopherus agassizii,
      during the reproductive cycle.
AB  - Blood samples from 30 female and 20 male adult desert tortoises, Gopherus
      agassizii, were collected at monthly intervals during the annual reproductive
      cycle (April to October). Plasma corticosterone and the sex steroids in each of
      the samples were analyzed by radioimmunoassay. Mean corticosterone levels in
      males were significantly higher than in females (P < 0.001) in every month. Male
      tortoises showed a marked seasonal pattern in plasma corticosterone with a highly
      significant peak in July, August, September, and October that corresponded with a
      similar peak in plasma testosterone. Testosterone and corticosterone in the male
      showed a highly significant correlation (P < 0.0001). The pattern of
      corticosterone in the female was less marked, with a significant peak in May
      during the mating and nesting season, but no association with the peak in
      estradiol in late summer was apparent. The highest levels of corticosterone in
      the males were associated with the peak in spermatogenesis and intense male-male
      combat. These results support similar data from other reptiles that suggest
      increased glucocorticoid secretion during periods of increased activity and
      metabolism.

PMID- 11241400
TI  - Variable effects of goitrogens in inducing precocious metamorphosis in sea
      lampreys (Petromyzon marinus).
AB  - The ability of different goitrogens (anti-thyroid agents) to induce precocious
      metamorphosis in larval sea lampreys (Petromyzon marinus) was assessed in four
      separate experiments. Two of these goitrogens (propylthiouracil [PTU] and
      methimazole [MMI]) are inhibitors of thyroid peroxidase-catalyzed iodination, and
      three (potassium perchlorate [KClO(4)], potassium thiocyanate [KSCN], and sodium
      perchlorate [NaClO(4)]) are anionic competitors of iodide uptake. Because,
      theoretically, all of these goitrogens prevent thyroid hormone (TH) synthesis, we
      also measured their influence on serum concentrations of thyroxine and
      triiodothyronine. All goitrogens except PTU significantly lowered serum TH
      concentrations and induced metamorphosis in some larvae. The incidence of
      metamorphosis appeared to be correlated with these lowered TH concentrations in
      that KClO(4), NaClO(4), and MMI treatments resulted in the lowest serum TH
      concentrations and the highest incidence of metamorphosis in sea lampreys.
      Moreover, fewer larvae metamorphosed in the KSCN and low-KClO(4) treatment groups
      and their serum TH concentrations tended to be greater than the values in the
      aforementioned groups. MMI treatment at the concentrations used (0.087 and 0.87
      mM) was toxic to 55% of the exposed sea lampreys within 6 weeks. The potassium
      ion administered as KCl did not alter serum TH concentrations or induce
      metamorphosis. On the basis of the results of these experiments, we have made the
      following conclusions: (i) In general, most goitrogens other than PTU can induce
      metamorphosis in larval sea lampreys, and this induction is coincident with a
      decline in serum TH concentrations. (ii) The method by which a goitrogen prevents
      TH synthesis is not directly relevant to the induction of metamorphosis. (iii)
      PTU has variable effects on TH synthesis and metamorphosis among lamprey species.
      (iv) Unlike in protochordates, potassium ions do not induce metamorphosis in sea
      lampreys and are not a factor in the stimulation of this event.

PMID- 11241402
TI  - Influence of diminished respiratory surface area on survival of sea turtle
      embryos.
AB  - It has been suggested that fungal presence on sea turtle eggs may impede gas
      exchange. To investigate the influence of diminished gas exchange surface upon
      embryo survivorship, flatback (Natator depressus) and green (Chelonia mydas) eggs
      were painted with petroleum jelly. Variable proportions of the egg surface were
      covered, including both respiratory and nonrespiratory domains. Embryo survival
      varied with site inhibited, proportion of eggshell affected, and species of
      turtle. If fungi on the exterior of the eggshell are able to impede respiratory
      gas exchange, their presence on the upper hemisphere (primary gas exchange area
      in early incubation) will result in the highest embryo mortality. Large eggs are
      likely to demonstrate a higher survivorship than small eggs, due to their larger
      available respiratory area and/or to variation in weight or stage-specific
      embryonic metabolic demands. Interspecific differences in egg size may therefore
      be a contributory factor to observed mortality rate differences in the natural
      presence of fungi.

PMID- 11241401
TI  - Chromatin reorganization during spermiogenesis of the mollusc Thais hemostoma
      (Muricidae): implications for sperm nuclear morphogenesis in cenogastropods.
AB  - Thais is a cenogastropod mollusc belonging to the Muricidae family. The sperm
      nuclear morphogenesis of Thais develops in two well-defined and peculiar steps.
      In the first one, the round early spermatidyl nucleus is penetrated by an
      endonuclear channel, which arranges as a helix at the inner nuclear surface and
      organizes the condensing chromatin all around. In the second step, the spiral
      channel stretches, dragging along the associated chromatin and leading to a
      definitive cylinder-shaped sperm nucleus. Simultaneously with these changes in
      nuclear shape, the chromatin is sequentially organized in granules, fibres,
      lamellae, and, finally, in a very condensed structure, whereas the spermiogenic
      DNA-associated proteins become more basic and simple. The sperm nucleus contains
      a small group of protamines consisting of only four types of amino acid (lysine,
      arginine, glycine, and serine). The most remarkable fact on nuclear
      spermiogenesis in Thais is that, whereas the chromatin condensation process, the
      nuclear proteins, and the final shape of sperm nucleus are very similar to those
      in other muricidae studied, the pathway of nuclear morphogenesis is completely
      different. We propose an independent genetic control for those two spermiogenic
      events (chromatin condensation and nucleomorphogenesis). Finally we discuss
      briefly the main traits of nucleomorphogenesis of muricid molluscs.

PMID- 11241403
TI  - Mouse-rabbit germinal vesicle transfer reveals that factors regulating oocyte
      meiotic progression are not species-specific in mammals.
AB  - A series of experiments were designed to evaluate the meiotic competence of mouse
      oocyte germinal vesicle (GV) in rabbit ooplasm. In experiment 1, an isolated
      mouse GV was transferred into rabbit GV-stage cytoplast by electrofusion. It was
      shown that 71.8% and 63.3% of the reconstructed oocytes completed the first
      meiosis as indicated by the first polar body (PB1) emission when cultured in M199
      and M199 + PMSG, respectively. Chromosomal analysis showed that 75% of matured
      oocytes contained the normal 20 mouse chromosomes. When mouse spermatozoa were
      microinjected into the cytoplasm of oocytes matured in M199 + PMSG and M199, as
      many as 59.4% and 48% finished the second meiosis as revealed by the second polar
      body (PB2) emission and a few fertilized eggs developed to the eight-cell stage.
      In experiment 2, a mouse GV was transferred into rabbit MII-stage cytoplast. Only
      13.0-14.3% of the reconstructed oocytes underwent germinal vesicle breakdown
      (GVBD) and none proceeded past the MI stage. When two mouse GVs were transferred
      into an enucleated rabbit oocyte, only 8.7% went through GVBD. In experiment 3, a
      whole zona-free mouse GV oocyte was fused with a rabbit MII cytoplast. The GVBD
      rates were increased to 51.2% and 49.4% when cultured in M199 + PMSG and M199,
      respectively, but none reached the MII stage. In experiment 4, a mouse GV was
      transferred into a partial cytoplasm-removed rabbit MII oocyte in which the
      second meiotic apparatus was still present. GVBD occurred in nearly all the
      reconstructed oocytes when one or two GVs were transferred and two or three
      metaphase plates were observed in ooplasm after culturing in M199 + PMSG for 8
      hr. These data suggest that cytoplasmic factors regulating the progression of the
      first and the second meioses are not species-specific in mammalian oocytes and
      that these factors are located in the meiotic apparatus and/or its surrounding
      cytoplasm at MII stage.

PMID- 11241404
TI  - Effects of spaceflight and cage design on abdominal muscles of male rodents.
AB  - We examined the effects of a 16-day spaceflight mission on the size of muscle
      fibers in the rectus abdominis, external oblique and transversus abdominis
      muscles of adult male Fisher rats. The rats were individually housed in orbit, in
      contrast to the one previous spaceflight investigation of the same muscles, where
      the rats were group-housed pregnant females. The cross-sectional area of the
      muscle fibers was used as a measure of muscle atrophy or hypertrophy. The
      transversus, which is presumed to be the primary expiratory muscle and
      consequently works against internal hydrostatic pressures that are not likely to
      change much between 1 G and weightlessness, did not change in size. However, both
      the rectus abdominis (a spinal flexor) and the external oblique (a rotator of the
      torso), which resist gravity in the 1 G environment, showed significant signs of
      atrophy after extended exposure to microgravity. The atrophy of the external
      oblique was diametrically opposite to hypertrophy of the same muscle observed in
      group-housed rodents previously exposed to spaceflight. Although the two missions
      differed in several factors, such as the gender of the rats and mission duration,
      we believe that housing of the animals was the key factor that accounted for the
      different responses of the external oblique. Previous research has shown that
      group-housed rats in spaceflight exhibited seven times more rotations of their
      torsos than matched ground controls. Thus unloading of the musculoskeletal system
      may not be achieved in weightlessness when animals have the freedom to interact
      with each other.

PMID- 11241405
TI  - Serrated route to colorectal cancer: back street or super highway?
AB  - Morphological and molecular studies are beginning to distinguish separate
      evolutionary pathways for colorectal cancer. The serrated pathway encompassing
      hyperplastic aberrant crypt foci, hyperplastic polyps, mixed polyps, and serrated
      adenoma is increasingly being linked with genetic alterations, including DNA
      methylation, DNA microsatellite instability, K-ras mutation, and loss of
      chromosome 1p. The importance of the serrated pathway has been underestimated in
      terms of its frequency and potential for rapid progression.

PMID- 11241406
TI  - Colorectal carcinoma associated with serrated adenoma--prevalence, histological
      features, and prognosis.
AB  - Serrated adenoma has been proposed to be a distinct entity among colorectal
      neoplasms. Progression to frank carcinoma has been suggested in individual cases,
      but the prevalence of carcinomas originating from serrated adenomas and their
      clinico-pathological characteristics are not known. In the present study, a large
      series of colorectal cancers was analysed for the occurrence of serrated adenoma
      in association with carcinoma and clinico-pathological features were compared in
      cases with and without serrated adenoma. Specimens from 466 colorectal carcinoma
      patients undergoing operations between 1986 and 1996 were re-evaluated for the
      presence of juxtaposed serrated adenoma and carcinoma. Clinico-pathological
      features such as location, Dukes' stage, histological grade, mucinous
      differentiation, and prognosis were evaluated. Twenty-seven carcinomas (5.8%)
      were found in association with an adjacent serrated adenoma. Eight of the
      patients were male and 19 were female. All of these adenocarcinomas showed a
      serrated appearance resembling that of serrated adenomas. Nine (33%) cases were
      mucinous and a mucinous component was present in 11 (41%) additional cases. The
      majority of the tumours were located either in the caecum (14 cases; 51%) or in
      the rectum (9 cases; 33%). DNA microsatellite instability was more common in
      carcinomas associated with serrated adenoma (37.5%) than in other carcinomas
      (11.0%). It is concluded that carcinoma associated with serrated adenoma is a
      distinct type of colorectal neoplasm, accounting for 5.8% of all colorectal
      carcinoma cases in this study. Predilection for the caecum and the rectum may
      reflect their aetiological factors. Female preponderance is contrary to that
      reported for hyperplastic polyps and serrated adenomas.

PMID- 11241407
TI  - Human papillomavirus variants and squamous neoplasia of the cervix.
AB  - Human papillomaviruses (HPVs) play a central role in the aetiology of cervical
      neoplasia. However, only a small proportion of cervical intraepithelial lesions
      infected with high-risk HPVs will progress to invasive cervical carcinoma, which
      indicates the involvement of additional factors. An important emerging viral
      factor is naturally occurring intratypic sequence variation. Such variation has
      been used to study the geographical spread of HPVs, but there is increasing
      evidence that it may be important in determining the risk of development of
      neoplastic disease. The collected data indicate that different HPV variants have
      altered biochemical and biological properties and represent an additional risk
      factor in the development of squamous intraepithelial lesions and invasive
      carcinoma of the cervix. This may be relevant not only to the biology of HPV
      infection and its association with squamous neoplasia, but also to the use of HPV
      typing in clinical practice.

PMID- 11241408
TI  - Molecular changes in the Ki-ras and APC genes in colorectal adenomas and
      carcinomas arising in the same patient.
AB  - The purpose of this study was to compare the molecular genetic changes in the Ki
      ras and adenomatous polyposis coli (APC) genes between adenomas and carcinomas
      removed from the same patients. This comparison of benign and malignant tissue
      would enhance understanding of the progression of molecular changes during the
      development of colorectal malignancy and similarities between paired lesions
      could be indicative of a common aetiology. The basic procedures used were DNA
      extraction from wax blocks of removed tissue, followed by polymerase chain
      reaction (PCR) and gel electrophoresis for mutations in the Ki-ras gene using
      single strand conformational polymorphism (SSCP); amplification of a CA repeat
      marker was used to assess for loss of heterozygosity (LOH) of the APC gene. The
      main findings in 100 adenoma and carcinoma pairs for the Ki-ras gene were as
      follows: the frequency of Ki-ras mutation in the adenomas increased with
      increasing villous component, but did not vary in the paired carcinomas; the
      frequency of Ki-ras mutation in villous adenomas was greater than in carcinomas;
      and when both paired lesions had Ki-ras mutations, only 44% had the identical
      mutation. For the APC gene, the incidence of LOH in the adenomas did not vary by
      histological type; the LOH status of the adenoma was associated with that of the
      paired carcinoma; but when both paired lesions had LOH of the APC gene, only 50%
      had LOH for the same allele. In conclusion, these data on paired adenomas and
      carcinomas suggest that a Ki-ras mutation is not a consistent finding between the
      adenoma and carcinoma from the same bowel. The development of LOH of the APC gene
      is a slightly more consistent finding between the pair, but is not always allelic
      specific.

PMID- 11241409
TI  - E-cadherin gene mutations in human intrahepatic cholangiocarcinoma.
AB  - Deletions or mutations of the E-cadherin gene may result in reduced cell
      adhesiveness. In particular, conservative point mutations within the N-terminal
      calcium-binding pocket (including exons 7, 8, and 9) are frequently detected in
      several cancers and are enough to abolish cell-cell adhesion. There have been no
      studies on E-cadherin gene mutations in human intrahepatic cholangiocarcinoma
      (ICC). Human ICCs were therefore investigated for E-cadherin gene mutations
      within exons 7, 8, and 9. In addition, the relationships were analysed between
      their mutations and the immunohistochemical expression of E-cadherin,
      histological grade, and clinicopathological parameters. The E-cadherin gene was
      analysed in 34 tumours by nested polymerase chain reaction/single-strand
      conformation polymorphism (PCR/SSCP) followed by DNA sequencing. In four of the
      34 cases (11.8%), tumour-restricted mobility shifts were observed; two cases
      harboured a single shift, one case presented two different mobility shifts, and
      one case presented three different mobility shifts within exons 7 and 8, encoding
      extracellular domains of E-cadherin. Polymorphism as previously reported was not
      identified and all seven new DNA alterations were not present in genomic DNA of
      non-tumour origin. The E-cadherin gene mutations correlated significantly with
      down-regulated E-cadherin protein expression and high ICC histological grade.
      These data suggest that E-cadherin gene mutations in ICC are associated with
      reduced cell adhesiveness and high histological grade.

PMID- 11241410
TI  - Histological and immunological parameters to predict treatment outcome of
      Helicobacter pylori eradication in low-grade gastric MALT lymphoma.
AB  - Helicobacter pylori eradication is generally accepted as the first choice of
      treatment for stage IE low-grade gastric MALT lymphoma (mucosa-associated
      lymphoid tissue-type lymphoma). Treatment failure may be attributed to the extent
      of the disease and to progression into an antigen-independent phase. This study
      assessed the value of morphological grading and the expression of the co
      stimulatory markers CD40, CD80 and CD86 and their ligands to predict clinical
      outcome in 23 consecutive low-grade MALT lymphoma patients treated with H. pylori
      eradication. Complete regression was achieved in 13/23 patients (56%), partial
      regression in two (9%), and no response in eight (35%). Histological grading was
      highly predictive of clinical response, especially in stage IE(1) patients, with
      complete remissions in 10/12 tumours with purely low-grade (type A) morphology
      and 1/8 tumours with increased numbers of blasts (type B) (p=0.0046) and was
      related to the expression of costimulatory markers (p=0.0061). Moreover, CD86 as
      a single marker proved to be of predictive value for treatment outcome
      (p=0.0086). These results suggest that morphological grading and immunological
      criteria can be defined to recognize the transition into the antigen-independent
      phase of gastric MALT-NHL. In addition to clinical stage, these critera may in
      future serve as a practical pathological guide to the choice of therapy.

PMID- 11241411
TI  - VEGF-B expression in human primary breast cancers is associated with lymph node
      metastasis but not angiogenesis.
AB  - Angiogenesis is essential for tumour growth and metastasis. It is regulated by
      numerous angiogenic factors, one of the most important being vascular endothelial
      growth factor (VEGF). Recently VEGF-B, a new VEGF family member that binds to the
      tyrosine kinase receptor flt-1, has been identified. Although the importance of
      VEGF has been shown in many human tumour types, the contribution of VEGF-B to
      tumour neovascularization is unknown in any tumour type. This study therefore
      measured the mRNA level of VEGF-B and its receptor flt-1 by ribonuclease
      protection assay and the pattern of VEGF-B expression by immunohistochemistry in
      13 normal breast samples and 68 invasive breast cancers. Flt-1 expression was
      significantly higher in tumours than in normal breast (p=0.02) but no significant
      difference was seen in VEGF-B between normal and neoplastic breast (p=0.3). There
      was a significant association between VEGF-B and node status (p=0.02) and the
      number of involved nodes (p=0.01), but not with age (p=0.7), size (p=0.6),
      oestrogen receptor (ER) (p=0.2), grade (p=0.5) or vascular invasion (p=0.16). No
      significant relationship was present between VEGF-B and flt-1 (p=0.2) or tumour
      vascularity (p=0.4). VEGF-B was expressed mostly in the cytoplasm of tumour
      cells, although occasional stromal components including fibroblasts and
      endothelial cells were also positive. No difference in VEGF-B expression was
      observed adjacent to regions of necrosis, in keeping with this VEGF family member
      not being hypoxically regulated. These findings suggest that VEGF-B may
      contribute to tumour progression by a non-angiogenic mechanism, possibly by
      increasing plasminogen activators and hence metastasis, as has been described in
      vitro. Measurement of VEGF-B together with other angiogenic factors may identify
      a poor prognostic patient group, which may benefit from anti-VEGF receptor
      therapy targeted to flt-1 (VEGFR1) as well as kdr (VEGFR2).

PMID- 11241412
TI  - Subgroups of non-atypical hyperplasia of breast defined by proliferation of
      oestrogen receptor-positive cells.
AB  - In normal breast, there is a negative association between expression of oestrogen
      receptor (ER) and the proliferation marker Ki67, indicating that ER-positive
      (ER+) cells do not divide, or that the receptor is down-regulated when they do
      so. However, dual staining has been found in carcinomas and precancerous lesions,
      indicating that abnormal regulation of ER could be important in breast
      tumourigenesis. ER expression in relationship to cell proliferation was studied
      in 241 foci of hyperplasia of usual type (HUT), a lesion associated with a 1.5 to
      2-fold increase in risk of developing breast cancer. Dual label
      immunofluorescence was employed, using the antibodies 1D5 and Ki67. Two hundred
      and thirteen foci of HUT contained ER+ cells, which were distributed singly or
      contiguously and increased with age. Most foci resembled normal breast, but 51
      contained dual labelled cells, which did not increase with age. Some of these
      foci exhibited few, scattered ER+ cells with greater proliferation rates than the
      ER-negative (ER-) cells, whereas others contained many, contiguous ER+ cells,
      whose rate of proliferation was less than that of the ER- cells. The latter
      picture is similar to that which has previously been reported in atypical ductal
      hyperplasia and ductal carcinoma in situ. The first type of HUT may evolve into
      the second. The proportion of Ki67+ cells that was ER+ was similar in both types,
      suggesting a homeostatic mechanism that slows the proliferation of ER+ cells as
      they become confluent. Overriding this inhibition may be crucial in further
      progression. Non-atypical hyperplasia is thus heterogeneous in ER expression and
      proliferation and a significant proportion exhibit abnormal regulation of ER.
      These findings could have implications for pathological diagnosis, risk
      assessment, and prophylactic hormonal therapy.

PMID- 11241413
TI  - Mucin gene transcripts in benign and borderline mucinous tumours of the ovary: an
      in situ hybridization study.
AB  - Mucinous tumours of the ovary are characterized by mucin-secreting cells
      exhibiting a variable endocervical, intestinal, gastric or pancreatobiliary
      phenotype as ascertained by microscopy, electron microscopy, histochemistry or
      immunohistochemistry. The molecular mechanisms underlying the tumourigenesis
      process are not well understood. The mucin glycoproteins expressed by ovarian
      mucinous tumours have not been fully characterized, but mucins are known to be
      implicated in tumour progression in various epithelial neoplasms. The purpose of
      this study was to evaluate the expression of mucin genes (MUC1, MUC2, MUC3, MUC4,
      MUC5AC, MUC5B, MUC6) in ovarian mucinous tumour cells, to relate MUC gene
      expression to the histological diagnosis, and to compare the expression patterns
      with those observed in normal tissues. The expression of mucin genes was
      evaluated by in situ hybridization in 21 mucinous tumours (11 adenomas and ten
      borderline tumours). Heterogeneity of expression correlated with morphological
      heterogeneity. Intense expression of the MUC5AC gene, suggesting a gastric
      surface cell phenotype, was demonstrated in 18/21 tumours (86%). Goblet cells
      expressing the MUC2 gene and columnar cells expressing the MUC3 gene were
      consistent with an intestinal phenotype, which was observed in 15 tumours (71%)
      including nine adenomas and six borderline tumours. Major expression of MUC4 and
      MUC5B consistent with an endocervical phenotype was observed in seven benign
      (64%) and three borderline (30%) tumours. In all, the MUC profiles suggested
      gastrointestinal-type cells in 13 cases (62%), gastric-type cells in five cases
      (24%), and intestinal-type cells in two cases (one benign, one borderline) (9%);
      the results were inconclusive in one borderline tumour (5%). It is concluded that
      gastric and, to a lesser degree, intestinal differentiation are early and almost
      constant events in ovarian mucinous tumourigenesis.

PMID- 11241414
TI  - CD44s and CD44v6 expression in localized T1-T2 conventional renal cell
      carcinomas.
AB  - To assess the prognostic value of CD44s and CD44v6 tumour expression for patients
      with T1-T2 conventional renal cell carcinomas, a retrospective
      immunohistochemical analysis of 95 patients was undertaken. These patients had
      undergone a radical nephrectomy, performed in three institutions in France
      between 1987 and 1993. The mean age of the patients was 62.9+/-10.2 years (range
      from 37 to 85 years) with 66.3% males. At the time of surgery, 84 patients had a
      T1 and 11 a T2 renal tumour. Fuhrman nuclear grading showed 44 (46.3%) tumours of
      grade 1, 39 (41.1%) of grade 2, and 12 (12.6%) of grade 3. The mean follow-up
      period was 58.1+/-36.1 months. At the end of follow-up, eight patients (8.4%) had
      metastatic disease and no local recurrence was seen. Immunohistochemistry showed
      that 26 tumours (27.4%) expressed CD44s, but none expressed CD44v6. Statistical
      analysis showed that CD44s expression was correlated with tumour size (p=0.006)
      and Fuhrman grading (p<10(-4)). Among the various parameters tested for the
      multivariate analysis, CD44s expression correlated only with disease-free
      survival (p=0.04). It is concluded that CD44s expression, but not CD44v6, is of
      potential prognostic interest in patients with localized T1-T2 conventional renal
      cell carcinomas.

PMID- 11241415
TI  - Limiting the diagnosis of atypical small glandular proliferations in needle
      biopsies of the prostate by the use of immunohistochemistry.
AB  - Prostatic biopsies containing small glandular formations suspicious of, but not
      diagnostic for, carcinoma represent a diagnostic dilemma, as they cannot be
      definitely identified as either benign or malignant. The term 'atypical small
      acinar proliferation' (ASAP) in the differential diagnosis of carcinoma has
      recently evoked considerable discussion. This study has tried to assess the
      biological potential of ASAP by further immunohistochemical (IHC) analysis.
      Biopsy-proven cases of ASAP (n=114) were analysed, in which consecutive sections
      still contained the suspicious lesion. IHC studies were undertaken with anti
      cytokeratin 34betaE12 and the proliferation marker MIB-1. Staining with 34betaE12
      revealed a complete basal cell layer in 25 cases (21.9%), a fragmented layer in
      58 cases (50.9%), and absence of basal cells in 31 cases (27.2%). MIB-1 labelling
      indices (LIs) in these three groups were significantly higher than in benign
      prostatic tissue (p<0.001) and reached the level of low-grade prostatic carcinoma
      (p>0.05). The suspicious morphology of ASAP on haematoxylin and eosin-stained
      slides was supported by the finding of elevated proliferative activity. Subgroups
      were revealed by immunohistochemical assessment of basal cell status and cases
      without basal cells were diagnosed as carcinoma. Nevertheless, rebiopsy is
      recommended if radical surgery is planned, to exclude insignificant cancer. Cases
      with a complete or fragmented basal cell layer were regarded as non-malignant.
      Whether a fragmented basal cell layer reflects a technical artefact or transition
      to carcinoma is unknown, but the proliferative activity of both lesions was
      increased and corresponded to that of low-grade prostatic carcinoma. In these
      cases, therefore, at least clinical follow-up is strongly recommended and repeat
      biopsies are encouraged.

PMID- 11241416
TI  - Chondrosarcoma is not characterized by detectable telomerase activity.
AB  - Reactivation of telomerase, an enzyme which elongates human telomeres, is
      associated with cell immortilization. In approximately 90% of malignant tumours
      telomerase activity can be demonstrated, whereas in benign tumours it is mostly
      absent. Chondrosarcomas are relatively rare malignant cartilaginous neoplasms. A
      small number of chondrosarcomas located centrally in bone arise secondarily to an
      enchondroma, while the majority of chondrosarcomas developing from the surface
      arise within the cartilage cap of an osteochondroma. The histological distinction
      between a benign lesion and low-grade chondrosarcoma is generally considered
      difficult. To investigate whether the progression towards chondrosarcoma is
      characterized by reactivation of telomerase activity, this study determined
      telomerase activity in ten enchondromas, five osteochondromas, and 37
      chondrosarcomas using the TRAP assay. In all tumour samples except one,
      telomerase activity was absent. By adding tumour lysates to the positive control,
      an increasing inhibition of telomerase activity was found with an increasing
      chondroid matrix, suggesting that it may contain inhibitory factors. Inhibition
      due to endogenous RNAse or Taq-polymerase inhibitors was excluded. The lack of
      detectable telomerase activity in the high-grade component of a dedifferentiated
      chondrosarcoma without matrix favours the possibility that telomerase is truly
      absent. Either its true absence or inhibitory effects disabling telomerase
      detection exclude the telomerase TRAP assay as a diagnostic tool in the
      differential diagnosis of benign and low-grade malignant cartilaginous tumours.

PMID- 11241417
TI  - Localization of androgen receptor expression in human bone marrow.
AB  - Androgens have been shown to modulate the haematopoietic and immune systems and
      have been used clinically for stimulating haematopoiesis in bone marrow failure
      conditions. To identify the bone marrow cell types as potential targets of
      androgens, an androgen receptor (AR)-specific antibody was used to localize the
      AR in normal human bone marrow biopsies. The results show that AR was
      ubiquitously expressed in the bone marrow of both males and females. Furthermore,
      the AR expression pattern did not change with age. Stromal cells, macrophages,
      endothelial cells, myeloblasts, myelocytes, neutrophils, and megakaryocytes
      expressed AR. In contrast, AR was not detected in the lymphoid and erythroid
      cells, or in eosinophils. These results indicate that androgens may exert direct
      modulating effects on a wide spectrum of bone marrow cell types via AR-mediated
      responses.

PMID- 11241418
TI  - Endothelial capillaries chemotactically attract tumour cells.
AB  - Directional migration of capillaries towards tumour implants is generally assumed
      to be regulated by chemotaxis. Preliminary evidence has also been presented for
      the existence of a reverse chemotactic signalling pathway, with capillaries
      attracting tumour cells via paracrine factors. By using a variety of endothelial
      cell types and tumour cell lines, this study has systematically investigated
      chemotaxis between endothelial cells and tumour cells in two- and three
      dimensional systems. Checkerboard analysis revealed faint attraction of human
      umbilical vein endothelial cells (HUVECs), but not porcine aortic endothelial
      cells (PAECs), by tumour cells. In reverse, both PAECs and HUVECs potently
      induced chemotactic migration of tumour cells. Using a microcarrier-based fibrin
      gel assay, directional migration of endothelial cells towards tumour cells was
      not observed. In reverse, tumour cells were strongly attracted by endothelial
      cells. Identification of endothelium-derived chemotactic molecules may provide a
      valuable approach for the treatment of tumour metastasis.

PMID- 11241419
TI  - Detection of apoptotic cells in archival tissue from diffuse astrocytomas using a
      monoclonal antibody to single-stranded DNA.
AB  - Precise quantitation of apoptotic cells in gliomas is necessary to determine the
      role of apoptosis in tumour growth, prognosis, and treatment. This study
      investigated the incidence of baseline apoptosis in relation to proliferation
      status, p53 expression, standard clinicopathological parameters, and outcome, in
      a series of 61 patients with diffuse cerebral astrocytomas. Apoptotic fractions
      were quantified immunohistochemically by means of a novel monoclonal antibody
      recognizing exposed single-stranded (ss) regions in the DNA of apoptotic cells
      during heating. Proliferative activity was expressed as the percentage of Ki-67
      positive cells. Tissues consisted of primary formalin-fixed, paraffin-embedded
      astrocytoma specimens. The apoptotic index (AI) increased with grade,
      proliferative activity, and p53 expression. Increased AI tended to be accompanied
      by a shortened overall and disease-free survival in univariate analysis in
      glioblastoma multiforme and astrocytoma/anaplastic astrocytoma, respectively.
      Multivariate analysis demonstrated that increased AI was an independent predictor
      of adverse significance in overall and disease-free survival. These results
      implicate apoptotic rate in astrocytoma aggressiveness and show that the
      assessment of apoptotic potential by means of anti-ssDNA monoclonal antibody
      provides valuable prognostic information independently of standard parameters or
      tumour proliferation status.

PMID- 11241420
TI  - CD8+ T cells infiltrating into bile ducts in biliary atresia do not appear to
      function as cytotoxic T cells: a clinicopathological analysis.
AB  - It is speculated that immune mechanisms are involved in bile duct damage in
      biliary atresia (BA), as in primary biliary cirrhosis (PBC). In BA, however, no
      reports have described the in situ distribution of cytotoxic T lymphocytes (CTLs)
      using specific markers, nor has the clinical association been clarified. The
      present study describes the immunohistochemical distribution of CD8+ T cells and
      the relevant markers [perforin, granzyme B, FasL (CD95L)] in 47 cases of BA
      operated upon at days 12-79. The results were compared with those of PBC. In BA,
      CD8+ T cells infiltrated bile ducts in a way similar to that observed in PBC.
      However, in sharp contrast to PBC, none of the inflammatory cells infiltrating
      into the bile ducts in BA expressed cytotoxic markers such as perforin, granzyme
      B, or Fas ligand (FasL). Clinical follow-up of patients with BA revealed that a
      greater degree of infiltration of bile ducts by CD8+ T cells is associated with
      better liver function. Taken together, these data suggest the absence of direct
      CTL activity against bile ducts in BA in the postnatal period.

PMID- 11241421
TI  - Smooth muscle inclusion bodies in slow transit constipation.
AB  - Slow transit constipation (STC) is a disorder of intestinal motility of unknown
      aetiology. Myopathies, including those characterized by the finding of inclusion
      bodies, have been described in enteric disorders. Amphophilic inclusion bodies
      have been reported in the muscularis externa of the colon of STC patients. This
      study formally tested the hypothesis that these represent a primary muscle
      disorder, specific to STC. In a systematic, blinded, dual observer qualitative
      and quantitative analysis, colonic and ileal tissue from patients with STC (n=36)
      were compared with selected control populations: total colonic aganglionosis
      (n=10), Chagas' disease (n=6), isolated rectal evacuation disorders (n=6), and a
      control population of a range of ages (n=80). All sections were stained with
      haematoxylin and eosin and periodic acid Schiff. Further immunostains were used
      in an attempt to determine inclusion body composition. Round or ovoid (4-22
      microm diameter) amphophilic inclusions increased in number in normal subjects
      with age. Inclusions were more frequent in idiopathic STC than in age-matched
      controls or rectal evacuation disorders [ileum (33% vs. 9%), ascending (50% vs.
      19%, p<0.05), and sigmoid colon (43% vs. 20%)] and were very frequent in the
      sigmoid (71%) of patients with STC arising after pelvic surgery. The number of
      inclusions per unit area was significantly higher in patients with STC (p<0.001).
      Inclusions were found in all Chagas' patients, but not with aganglionosis. It was
      not possible to determine inclusion body composition, despite the use of a wide
      range of conventional and immunostains. This study demonstrates that inclusion
      body myopathy is identifiable in patients with STC and that it may arise
      secondary to denervation.

PMID- 11241422
TI  - Smooth muscle cell modulation and cytokine overproduction in varicose veins. An
      in situ study.
AB  - The exact aetiology and physiopathology of varicose disorders remain unclear. The
      aim of the present work was to study, in situ, the morphology and composition of
      cellular and matrix components in varicose veins compared with control veins and
      to identify factors that could contribute to varicose remodelling. A combined
      histological, immunohistochemical, and biochemical approach was used.
      Longitudinal sections of varicose (n=12) and control veins (n=9) were studied to
      assess the organization, structure, and phenotype of smooth muscle cells; the
      localization of microvascular endothelial cells; the distribution of connective
      tissue proteins; and the localization of cytokines. These cytokines were further
      quantified by ELISA. Considerable heterogeneity of the varicose vein wall was
      observed, with a succession of hypertrophic and atrophic segments, presenting
      severe disorganization of the medial layer and numerous areas of intimal
      thickening. In hypertrophic portions, medial smooth muscle cells showed marked
      alterations suggesting modulation from a contractile to a proliferative and
      synthetic phenotype; furthermore, the number of vasa vasorum was increased. In
      contrast, in atrophic portions, both cellular and matrix components were
      decreased. TGFbeta1 (p< or =0.005) and bFGF (p< or =0.001) were increased and
      VEGF was not significantly modified in varicose veins when the results were
      expressed per mg of DNA. These results show that phenotypic modulation of smooth
      muscle cells, altered extracellular matrix metabolism, and angiogenesis are the
      main mechanisms contributing to the morphological and functional modifications of
      varicose remodelling. The increased expression of bFGF and TGFbeta1 by varicose
      vein cells may play a pivotal role in the hypertrophy of the venous wall, but the
      exact mechanism leading to aneurysmal dilatations remains to be elucidated.

PMID- 11241423
TI  - The effect of myocardial bridging of the coronary artery on vasoactive agents and
      atherosclerosis localization.
AB  - The relationship between alterations in the immunohistochemical expression of
      three vasoactive agents [endothelial nitric oxide synthase (eNOS), endothelin-1
      (ET-1), and angiotensin-converting enzyme (ACE)] and the occurrence human
      atherosclerosis was investigated in relation to the myocardial bridge (MB) of the
      left anterior descending coronary artery (LAD), an anatomical site that
      experiences increased shear stress. Five millimetre cross-sections of LADs with
      MB from 22 autopsied cases were taken from the left coronary ostium to the
      cardiac apex and were immunohistochemically stained with antibodies against eNOS,
      ET-1, and ACE. The extent of atherosclerosis in each section was calculated using
      the atherosclerosis ratio (intimal cross-sectional area/medial cross-sectional
      area) determined by histomorphometry. The results were analysed according to
      their anatomical location relative to the MB, either proximal, beneath, or
      distal. The extent of atherosclerosis was significantly lower beneath the MB,
      compared with proximal and distal segments. The expression of eNOS, ET-1, and ACE
      was also significantly lower beneath the MB. The expression of these agents
      correlated significantly with the extent of atherosclerosis. Because nitric
      oxide, after its production by eNOS, is believed to be degraded by superoxide
      radicals, the effect of eNOS expression on atherosclerosis remains controversial.
      However, the present findings clearly indicate that the expression of ET-1 and
      ACE is directly related to the development of human coronary atherosclerosis in
      vivo through shear stress.

PMID- 11241424
TI  - A comparative study of morphological changes in spontaneously hypertensive rats
      and normotensive Wistar Kyoto rats treated with an angiotensin-converting enzyme
      inhibitor or a calcium-channel blocker.
AB  - It is not clear whether some pathological changes in hypertension are directly
      pressure-dependent, or hormonally induced, or both. The aortic arch has
      apparently never before been studied for those changes. The aim of this study was
      to compare the effects of controlling angiotensin II (Ang II) and/or blood
      pressure (BP), directly at the inception of hypertension, on the aortic arch, the
      left ventricle of the heart (LV), and the kidneys of spontaneously hypertensive
      rats (SHRs) and normotensive Wistar Kyoto (WKY) rats. An angiotensin-converting
      enzyme inhibitor (ACEI, enalapril) and a calcium-channel blocker (nifedipine)
      were used for 21 weeks. After treatment, rats were assessed for arterial plasma
      renin activity (PRA). The LV, aortic arch, and kidneys were then excised for the
      determination of organ and tissue weight in some of the animals, while in others
      the aortic arch was fixed in situ and processed for microscopic analysis. Both
      enalapril and nifedipine levelled BP in the SHRs to almost normal values.
      Enalapril was able to prevent the increase in LV and kidney weights (p=0.04 wet,
      p<0.001 dry; p<0.001 wet and dry, respectively) and the increase in the weight of
      the aortic arch and in the thickness of its media (p<0.001 wet and dry; p<0.001,
      respectively) seen in untreated SHRs. This was associated with a larger lumen
      diameter (p<0.001) and a lower media to lumen ratio (p=0.01). In contrast,
      nifedipine did not prevent any of the changes described. Neither nifedipine nor
      enalapril treatment had any effects on PRA in either rat strain. Our results
      support previous observations that BP is not the only factor causing some of the
      pathological changes in hypertension; tissue Ang II level may also play a major
      role.

PMID- 11241425
TI  - C9 immunohistology in detection of myocardial infarction.

PMID- 11241428
TI  - 13-cis-retinoic acid causes patterning defects in the early embryonic rostral
      hindbrain and abnormal development of the cerebellum in the macaque.
AB  - BACKGROUND: We have previously reported that exposure of embryos to 13-cis
      retinoic acid (cRA) results in an abnormal phenotype of the fetal cerebellum. In
      this study, we analyzed early changes in the cerebellar anlagen (midbrain
      hindbrain junction) as well as lesions of the fetal cerebellar vermis after a
      teratogenic dosing regimen of cRA in the macaque model. METHODS: We examined
      embryo coronal sections of the midbrain-hindbrain junction immunostained for Pax
      2, Engrailed-2 (En-2) and Krox-20. To characterize the cerebellum foliation and
      fissure formation processes, we analyzed vermal cortical cell layer development
      and the number and depth of the major fissures on sagittal sections of fetal
      vermis. We also examined Purkinje cell development in vermal sections
      immunostained for CD3. RESULTS: Compared with controls, there was a consistent
      truncation of the midbrain-hindbrain region of early embryos exposed to cRA. The
      cRA-induced fetal vermis lesions included inhibition in its anteroposterior
      growth, altered folial patterning, a general loss of prominence of the fissures
      accompanied by a total loss of sublobular fissures, and changes in cortical cell
      layer development. CD3(+) Purkinje cells were abnormally dispersed deep into the
      molecular layer in the vermis. CONCLUSIONS: Our findings indicate that the
      effects of cRA on the developing cerebellum involve interference with the
      hierarchy of complex cellular and genetic interactions that lead to the growth
      and subdivision of the cerebellum into smaller units. The regional vermal defects
      may be related to early postnatal functional deficits.

PMID- 11241429
TI  - A thoracal spinal cord teratoma associated with Taussig-Bing anomaly in a
      newborn.
AB  - BACKGROUND: Teratomas are the most common type of childhood germ cell tumor,
      arising in both ovary and extragonadal locations. From 40% to 50% of the
      extragonadal teratomas occur in the sacrococcygeal region. Teratomas in the head,
      neck, brain, mediastinum, abdominal, and spinal cord locations are seen less
      frequently. Congenital anomalies are observed up to 26% of the cases with
      teratoma. METHODS: A 2-day-old newborn was admitted to the hospital because of a
      mass in the interscapular region. She was evaluated for this and other anomalies.
      The mass was excised totally, and histopathologic evaluation was done. RESULTS:
      Histopathologic examination of the mass revealed a mature teratoma. In addition,
      the child had a Taussig-Bing anomaly of the heart. CONCLUSIONS: This appears to
      be the first report of the association between congenital thoracic spinal cord
      teratoma and Taussig-Bing anomaly, a specific type of transposition of the great
      arteries.

PMID- 11241430
TI  - Maternal multivitamin use and orofacial clefts in offspring.
AB  - BACKGROUND: Cleft lip with or without cleft palate (CLP) and cleft palate alone
      (CP) affect approximately 1 in 1000 infants and 1 in 2,500 infants, respectively.
      Studies of the relation between orofacial clefts and multivitamins or folic acid
      have been inconsistent. METHODS: We used data from a population-based case
      control study involving 309 nonsyndromic cleft-affected births (222 with CLP, 87
      with CP) and 3,029 control births from 1968 to 1980 to evaluate the relation
      between regular multivitamin use and the birth prevalence of orofacial clefts.
      RESULTS: We found a 48% risk reduction for CLP (odds ratio = 0.52, 95% confidence
      interval = 0.34-0.80) among mothers who used multivitamins during the
      periconceptional period or who started multivitamin use during the first
      postconceptional month, after controlling for several covariates. The risk
      reduction for CP was less than those for CLP (odds ratio = 0.81, 95% confidence
      interval = 0.44-1.52); however, a small number of CP cases limited
      interpretation. No risk reductions for CLP or CP were found for women who began
      multivitamin use in the second or third month after conception. CONCLUSIONS: The
      magnitude of the risk reduction in our study is comparable to those of other
      recent studies; our study does not support the contention that only large dosages
      of folic acid are needed to prevent orofacial clefts. More studies are needed to
      test the effects of multivitamins and varying dosages of folic acid on the
      recurrence and/or occurrence of orofacial clefts to provide information needed to
      determine possible prevention strategies. Published 2001 Wiley-Liss, Inc.

PMID- 11241432
TI  - Partial caudal duplication in a newborn associated with meningomyelocele and
      complex heart anomaly.
AB  - BACKGROUND: Caudal duplication is a spectrum of rare congenital anomalies with a
      possible heterogeneous pathogenesis including incomplete separation of monovular
      twins. METHODS: We report an autopsy case of a full-term infant with incomplete
      caudal duplication syndrome associated with multiple anomalies. RESULTS: These
      anomalies included a duplicated penis; double urinary bladder with an attenuated
      tunica muscularis; duplication of lower bowel with two ilia, appendices and
      colons; colonic hypogangliosis and left imperforated anus associated with
      rectourethral fistula. Other anomalies consisted of sacral meningomyelocele,
      sacral duplication with hypoplastic left sacrum and pelvic bones, muscle atrophy
      and hypoplasia of the left lower extremity, abnormal lobation of liver with
      stomach entrapment, omphalocele, and right atrial isomerism syndrome. The complex
      pattern of anomalies suggests the possibility that partial caudal duplication
      might be part of the spectrum of conjoined twinning.

PMID- 11241431
TI  - Atrioventricular septal defects: possible etiologic differences between complete
      and partial defects.
AB  - BACKGROUND: Recent advances in clinical, pathological, and genetic aspects of
      atrioventricular septal defects (AVSD) have set the stage for epidemiologic
      investigations into possible risk factors. Previous analyses of the total case
      group of AVSD included complete and partial subtypes without analysis of the
      subsets. METHODS: To address the question of possible morphogenetic heterogeneity
      of AVSD, the Baltimore-Washington Infant Study data on live-born cases and
      controls (1981-1989) was reanalyzed for potential environmental and genetic risk
      factor associations in complete AVSD (n = 213), with separate comparisons to the
      atrial (n = 75) and the ventricular (n = 32) forms of partial AVSD. RESULTS:
      Complete and ventricular forms of AVSD had a similar proportion of isolated cases
      (12.2% and 15.6%, respectively, without associated extracardiac anomalies) and
      high rates of Down syndrome, whereas the atrial form of partial AVSD included 55%
      isolated cases. Trisomy 18 occurred in 22% of infants with the ventricular form,
      compared with <2% in the other AVSD groups. Analysis of potential risk factors
      revealed further distinctions. Complete AVSD as an isolated cardiac defect was
      strongly associated with maternal diabetes (odds ratio [OR] = 20.6; 95%
      confidence interval [CI] =5.6-76.4) and also with antitussive use (OR = 8.8; CI =
      1.2-48.2); there were no strong associations other than maternal age among Down
      syndrome infants with this type of heart defect. Isolated cases with the atrial
      type of partial AVSD were associated with a family history of heart defects (OR =
      6.2; CI = 1.4-24.4) and with paternal occupational exposures to ionizing
      radiation (OR = 5.1; CI = 1.4-27.4), but no risk factors were associated with
      Down syndrome. There were no significant associations of any risk factors in the
      numerically small subsets of isolated and Down syndrome cases with the
      ventricular form of partial AVSD. CONCLUSIONS: These results indicate a similar
      risk profile of complete AVSD and the ventricular type of partial AVSD, with a
      possible subset of the latter due to trisomy 18. Maternal diabetes constituted a
      potentially preventable risk factor for the most severe, complete form of AVSD.

PMID- 11241433
TI  - The history of the editorship of Teratology during the period from July 1, 1976
      to January 1, 1993.

PMID- 11241434
TI  - Teratogen update: reproductive risks of leflunomide (Arava); a pyrimidine
      synthesis inhibitor: counseling women taking leflunomide before or during
      pregnancy and men taking leflunomide who are contemplating fathering a child.

PMID- 11241436
TI  - Molecular discrimination between relapsed and secondary acute lymphoblastic
      leukemia: proposal for an easy strategy.
AB  - BACKGROUND: Discrimination between late relapse of acute lymphoblastic leukemia
      (ALL) and secondary ALL might be clinically important, because the former might
      still respond favorably to chemotherapy and/or bone marrow transplantation,
      whereas secondary ALL is associated with poor prognosis. PROCEDURE: We present a
      pre-B-ALL patient in whom disease recurred 2 years after completion of treatment.
      Differences in cytomorphology and immunophenotyping raised a suspicion of
      secondary ALL. We performed detailed molecular studies of immunoglobulin and T
      cell receptor genes for discrimination between relapsed and secondary ALL.
      RESULTS: Southern blot analysis showed an oligoclonal immunoglobulin heavy chain
      (IGH) gene configuration at diagnosis and a monoclonal configuration at relapse.
      The size of one of the rearranged bands at relapse was identical to one of the
      faint rearranged bands at diagnosis. However, heteroduplex PCR analysis
      demonstrated that none of the clonal IGH gene rearrangements at diagnosis and at
      relapse was fully identical. Sequencing of several clonal PCR products revealed
      an identical DH6-13<-->JH6b junction shared by two different rearrangements at
      diagnosis and one rearrangement at relapse, thereby proving the clonal
      relationship between diagnosis and late relapse in this patient. CONCLUSIONS: We
      propose a stepwise molecular approach for discrimination between relapsed and
      secondary ALL based on the rapid and cheap heteroduplex PCR technique, including
      mixing of clonal (homoduplex) PCR products identified at diagnosis and at
      relapse. Direct sequencing and comparative sequence analysis of IGH gene
      rearrangements at diagnosis and at relapse should be regarded as an ultimate
      standard, but can be limited to the rare cases, in which no identical clonal PCR
      products at diagnosis and at relapse were detected with the mixed heteroduplex
      PCR analyses.

PMID- 11241435
TI  - Motor nervous pathway function is impaired after treatment of childhood acute
      lymphoblastic leukemia: a study with motor evoked potentials.
AB  - BACKGROUND: The objective was to evaluate whether motor nervous pathways are
      affected when patients are treated for childhood acute lymphoblastic leukemia
      (ALL). PROCEDURE: Thirty-two children with ALL were studied at the end of
      treatment by means of motor evoked potentials (MEPs) elicited by magnetic
      stimulation (MS) transcranially and peripherally and underwent a detailed
      neurological examination. Thirty-two healthy children matched with them for age,
      sex, and height served as a control group. RESULTS: The latencies of the MEPs
      were significantly prolonged along the entire motor nervous pathway in the
      patients with ALL compared with the healthy controls, indicating demyelination in
      the thick motor fibres. The MEP amplitudes of the distal extremities elicited by
      stimulation at the brachial plexus and LV spinal level were significantly lowered
      in the patients treated for ALL, also indicating anatomical or functional loss of
      descending motor fibres and/or muscle fibres. The MEP amplitudes elicited by
      cortical MS showed wider variation and no clear abnormalities were found.
      Neurological signs and symptoms were common after treatment: 41% of the patients
      had depressed deep tendon reflexes, 31% had fine motor difficulties and 63% gross
      motor difficulties, and 34% had dysdiadochokinesia. The conduction delay within
      the peripheral nerve was related to the post-therapeutic interval after
      administration of vincristine and the lesions within the CNS to the number of
      injections of intrathecal methotrexate. CONCLUSIONS: The present results show
      adverse effects of the ALL treatment on the entire motor nervous pathways. In our
      experience, the measurement of MEPs by MS provides an objective, painless, and
      practical tool for assessing the treatment-related neurotoxicity in both the CNS
      and the peripheral nerves. These disturbances in the motor nervous pathways at
      the end of treatment raise the question of the long-term effects of ALL treatment
      on the motor nerve tracts, and have led us to employ MEPs to study these effects
      in long-term survivors of ALL.

PMID- 11241437
TI  - Expression of adhesion molecules LFA-1, ICAM-1, CD44, and L-selectin in childhood
      non-Hodgkin lymphomas.
AB  - BACKGROUND: The aim of the present study was to analyse the expression of
      adhesion molecules in childhood non-Hodgkin lymphomas and to correlate the
      findings with clinical features and prognosis. PROCEDURE: Samples were obtained
      from pleural and peritoneal fluids, bone marrow aspirates, and tissue biopsies
      from 21 patients (median age: 8 years). There were 9 T-cell and 12 B-cell
      lymphomas. The expression of CD18, CD44s, CD54, CD62L were investigated with flow
      cytometry by using monoclonal antibodies. RESULTS: Absence of CD18, which was
      independent from immunophenotype, was found in 67% of patients. Positive CD44s
      and CD62L expression were observed in 48 and 63% of the cases, respectively. In
      all of the cases with T-cell lymphoma, CD54 was negative, whereas 8 of 12 cases
      with B-cell lymphoma expressed this molecule (P = 0.005). There was no
      correlation between location of disease and the expression of adhesion molecules,
      except CD54 that was negative in all mediasten lymphoma (P = 0.004). CD62L (+)
      patients had more frequently stage IV disease than CD62L (-) ones (P = 0.01). Two
      year overall survival was 83 and 29% in CD18 (+) and CD18 (-) cases; 55 and 36%
      in CD44s (+) and CD44s (-) cases; 46 and 42% in CD54 (+) and CD54 (-) cases; 42
      and 50% in CD62L (+) and CD62L (-) cases. CONCLUSIONS: The expression of LFA-1 on
      lymphoblasts is lost in the majority of childhood non-Hodgkin lymphomas. ICAM-1
      is not detected on neoplastic cells of patients with T-cell lymphoblastic
      lymphoma. L-selectin positivity correlates with disseminated disease. There is no
      significant relationship between the expression of adhesion molecules and the
      survival rates, although CD18(+) cases had better overall survival rate than
      CD18(-) cases.

PMID- 11241438
TI  - A demographic study of the clinical significance of minimal residual disease in
      children with acute lymphoblastic leukemia.
AB  - BACKGROUND: Minimal residual disease (MRD) detected during remission might
      predict outcome in children with acute lymphoblastic leukemia. No population
      based studies have been carried out. We studied all children with ALL presenting
      over 5 years within a defined population to determine its clinical importance.
      PROCEDURE: Patients were investigated for the presence of unique clonal
      rearrangements of IgH and T-cell receptor genes. Unique patient specific probes
      were used to detect, by polymerase chain reaction, the presence of clonal markers
      indicating MRD in mononuclear cells obtained from marrow samples at 1, 3, 5, and
      24 months. The effect of MRD on event-free survival was determined. RESULTS:
      Seventy-seven of 120 children with ALL had informative markers and samples of
      remission marrow suitable for testing. Presence or absence of MRD did not
      significantly affect outcome. Gender (P < 0.04) and white cell count (P < 0.04)
      were independent prognostic factors. Analysis of only those cases with detectable
      MRD showed that cases with one blast per 100 mononuclear cells, or more, 28 days
      after starting treatment did worse than those with lower levels (hazard ratio
      7.77, P < 0.02). CONCLUSIONS: Mere presence or absence of MRD is probably too
      crude a measure to be useful and worse than other standard prognostic indicators.
      A threshold of 10(-2) blasts at 28 days might be discriminatory, but should not
      be over-interpreted. The number of patients available for this analysis (31) was
      small, the threshold and sampling points were arbitrary and any effects could be
      treatment regimen-specific. Large prospective studies are needed.

PMID- 11241439
TI  - Lumbar puncture in pediatric oncology: conscious sedation vs. general anesthesia.
AB  - BACKGROUND: Lumbar punctures (LP) generally have been performed with conscious
      sedation (CS) but are increasingly performed using general anesthesia (GA) owing
      to the belief that this is less distressing. The aim of this study was to compare
      these two methods concerning distress, discomfort, pain, well-being and security
      after the LP, and problems with the LP. PROCEDURE: Twenty-five children with
      cancer participated in this prospective, randomized, crossover study. Children,
      parents, and nurses completed a visual analogue scale questionnaire to evaluate
      the efficacy of CS and GA. In addition, sedation and anesthesia protocols were
      reviewed. RESULTS: The two methods seemed to be equivalent concerning distress,
      discomfort, pain, well-being and security after the procedure, and procedure
      problems. Most children (80%), parents (66%), and nurses (58%) preferred LP in
      CS. However, the LP was not performed in CS in five cases because the child did
      not cooperate. Younger children less often preferred CS. CONCLUSIONS: Outcomes
      for CS and GA in LP were similar. Although there were failures with the CS model,
      most preferred it to GA. LP in CS also saved time and medical resources. An
      alternative approach would be to have a pediatric anesthesiologist available at
      the oncology ward for these elective LPs to provide the sedation or anesthesia
      required by each individual.

PMID- 11241440
TI  - Proceedings of an international research workshop on pediatric liver tumours, 18
      20 March 1999, Berne, Switzerland. Into the year 2000.

PMID- 11241441
TI  - Childhood acute leukemia: a single institution experience in La Plata, Argentina.

PMID- 11241443
TI  - An infant with t(4;11)(q21;q23) acute lymphoblastic leukemia successfully treated
      using immunomagnetically purged autologous bone marrow transplantation.

PMID- 11241442
TI  - Two Victorian ladies and military medicine.

PMID- 11241444
TI  - Secondary acute lymphoblastic leukemia in a child three years after treatment for
      medulloblastoma.

PMID- 11241445
TI  - Primary lymphoma of the pituitary stalk in an immunocompetent 9-year-old child.

PMID- 11241447
TI  - The vanishing bile duct syndrome in a child with Hodgkin disease.

PMID- 11241448
TI  - Gilbert syndrome revealed during chemotherapy.

PMID- 11241446
TI  - Early occurrence of a secondary thyroid carcinoma in a child treated for Hodgkin
      disease.

PMID- 11241449
TI  - A fatal lymphoproliferative disorder primarily involving the lungs of a child.

PMID- 11241450
TI  - Neoadjuvant chemotherapy in osteosarcoma: the experience at the Hospital Infantil
      de Mexico from August 1996 to August 1999.

PMID- 11241451
TI  - Linitis plastica presenting as malignant ascites.

PMID- 11241452
TI  - Histiocyte Society and Nikolas Symposium. Amsterdam, The Netherlands, September
      29-October 2, 2000. Abstracts.

PMID- 11241456
TI  - Differences in HCV antibody patterns in haemodialysis patients infected with the
      same virus isolate.
AB  - Eight cases of de novo hepatitis C virus (HCV) infection in a haemodialysis unit
      in Rio de Janeiro, Brazil, were retrospectively studied. HCV viraemia was
      demonstrated by RT nested PCR in seven of the seroconverters. Genotyping showed
      that six patients were infected with a genotype 1b strain and one with a genotype
      1a strain. A phylogenetic analysis of nucleotide sequences of the HCV core region
      revealed that five of the six 1b isolates form a separate cluster when compared
      with other 38 HCV 1b core sequences randomly chosen from the GenBank. The
      revealed sequence similarities indicated the nosocomial spread of a single HCV
      strain within the unit. To investigate whether the patients infected with the
      same viral isolate display similar patterns of antibody response to individual
      proteins, serial serum samples were examined. A line immunoassay for qualitative
      and semi-quantitative determination of specific antibodies against recombinant
      and synthetic HCV antigens was employed. Despite infection with the same virus
      strain, the patients sera demonstrated different patterns of reactivity against
      individual structural and nonstructural HCV proteins immediately after
      seroconversion. For each patient, however, antibody responses remained mostly
      stable throughout the follow-up of 8 to 24 months.

PMID- 11241457
TI  - Serological diagnosis of Epstein-Barr virus infection by novel ELISAs based on
      recombinant capsid antigens p23 and p18.
AB  - A new pair of Epstein-Barr virus ELISAs (Biotest Anti-EBV VCA IgG and VCA IgM
      ELISA) was evaluated for usefulness for routine diagnosis of acute EBV
      infections. The ELISAs are based on two viral capsid antigens (VCA), p23 (BLRF2,
      full-length) and p18 (BFRF3, carboxy-half), that are combined by autologous gene
      fusion. In total, 179 sera were tested in direct comparison with classical VCA
      immunofluorescence assays (IFA). With the help of clinical data and additional
      reference serology, i.e., heterophile antibodies, anti-EA IgG (IFA) and anti-EBNA
      1 IgG (ELISA), the patients were divided into the following categories:
      seronegatives (46), acute primary infections (67), previous infections (39),
      suspected reactivations (20) and constellations with intermediate serological
      patterns (7). The VCA IgG and VCA IgM ELISAs showed overall agreement to IFA of
      95.0% and 94.4%, respectively. The calculated analytical performance
      (sensitivity; specificity) of VCA IgG and VCA IgM was 94.0%; 97.8% and 97.1%;
      96.5%, respectively. A certain delay in seroconversion of anti-p23-p18 IgG may
      account for a significant difference in sensitivity of the VCA IgG ELISA between
      primary (88.4%) and previous infections (100%). In summary, the new recombinant
      VCA ELISAs yielded good correlation to VCA IFA and in combination with EBNA-1 IgG
      allow rapid, sensitive, and specific diagnosis of infectious mononucleosis or EBV
      immune status in general.

PMID- 11241458
TI  - Human herpesvirus 7 is latent in gastric mucosa.
AB  - Chronic gastritis is associated frequently with persistent infection by
      Helicobacter pylori. However, not all patients with chronic gastritis have
      evidence of H. pylori infection, suggesting that other factors might contribute
      to the development of gastritis. The present study was undertaken to evaluate a
      possible etiologic role of human herpesvirus 7 (HHV-7). HHV-7 DNA was detected in
      about 80% of gastric biopsies, both in healthy mucosa from individuals without
      evidence of inflammation and in biopsies from patients with histologically
      confirmed chronic gastric inflammation. HHV-7 was present also in H. pylori
      negative samples, was associated specifically with gastric tissue and not with
      residual blood within the mucosa, and was present with high viral loads. HHV-7
      DNA persisted in several patients also after remission of gastric inflammation
      and the viral presence did not correlate with specific symptoms. Analysis by RT
      PCR showed that HHV-7 is transcriptionally inactive in chronic gastritis lesions.
      These observations show that gastric tissue represents a site of HHV-7 latent
      infection and a potential reservoir for viral reactivation.

PMID- 11241459
TI  - Human papillomavirus (HPV) study of 691 pathological specimens from Quebec by PCR
      direct sequencing approach.
AB  - Human papillomaviruses (HPV) are etiological agents of cervical cancer. In order
      to address clinical demand for HPV detection and sequence typing, mostly in pre
      cancerous cervical lesions, we applied our two-tier PCR-direct sequencing (PCR
      DS) approach based on the use of both MY09/MY11 and GP5 + /GP6 + sets of primers.
      We tested 691 pathological specimens, all of which were biopsies, 75% of which
      were diagnosed histologically as cervical intraepithelial neoplasia (CIN) grades
      I-III. In total, 484 samples (70%) tested HPV-positive, yielding 531 HPV
      sequences from 47 HPV types, including two novel types. Four most frequently
      found HPV types accounted for 52.9% of all isolates: HPV6, 16, 11, and 31 (21.5%,
      20.0%, 7.0%, and 4.5%, respectively). Some interesting results are the following:
      all currently known high-risk HPV (14 types) and low-risk HPV (6 types) were
      detected; HPV18 was not the 1st or 2nd but rather the 4th-5th most frequent high
      risk HPV type; the highest detection rate for HPV (86%) among samples suspected
      to be HPV-infected was found in the youngest age group (0-10 years old),
      including 70% (44/63) "genital" HPV types; HPV types of undetermined cervical
      cancer risk represented 19% and of the total HPV isolates but were strongly
      increased in co-infections (36.5% of all isolates). To our knowledge, this is the
      largest sequencing-based study of HPV. The HPV types of unknown cancer risk,
      representing the majority of the known HPV types, 27 of the 47 types detected in
      this study, are not likely to play a major role in cervical cancer because their
      prevalence in CIN-I, II, and III declines from 16% to 8% to 2.5%. The two-tier
      PCR-DS method provides greater sensitivity than cycle sequencing using only one
      pair of primers. It could be used in a simple laboratory setting for quick and
      reliable typing of known and novel HPV from clinical specimens with fine sequence
      precision. It could also be applied to anti-cancer vaccine development.

PMID- 11241460
TI  - Randomized controlled trial of seroresponses to double dose and booster influenza
      vaccination in frail elderly subjects.
AB  - Responses to influenza vaccination are poor in frail elderly subjects who suffer
      the greatest morbidity and mortality due to infection. Therefore, a randomized
      clinical trial was performed to determine the effect of a double dose and booster
      vaccination on antibody responses after influenza vaccination. A total of 815
      patients (median age 83 years, median disability score 8, median disease
      categories 2 and median number of medications 4) residing in 14 nursing homes in
      the Netherlands were vaccinated during the influenza season 1997-98. The first
      vaccine dose (15 or 30 microg) was given on Day 0 followed by a booster dose
      (placebo or 15 microg) on Day 84. Blood samples were taken before and 25 days
      after vaccination. There were four treatment groups: (i) 15 microg and placebo,
      (ii) 15 microg and 15 microg booster, (iii) 30 microg and placebo and (iv) 30
      microg and 15 microg booster. Geometric mean antibody titers of those receiving
      the double vaccine dose was 15% (95% CI, 6% to 24%, P = 0.001) higher as compared
      to the standard 15 microg dose. A booster dose, given 84 days after the first
      vaccination, yielded postvaccination titters that were 14% (95% CI, 9% to 19%, P
      = 0.001) higher as compared to placebo. Subgroup analysis did not reveal patient
      groups that had a proportionally greater benefit from adapted vaccination
      strategies. It is concluded that higher antibody responses can be achieved in
      frail elderly people by a double vaccine dose or a booster vaccination.

PMID- 11241461
TI  - Genomic characterization of wild-type measles viruses that circulated in
      different states in Brazil during the 1997 measles epidemic.
AB  - Despite the marked reduction in the incidence of measles in Brazil, a measles
      epidemic occurred in this country in 1997. The measles cases observed during this
      epidemic began to reappear in large numbers in Sao Paulo, and spread to Rio de
      Janeiro and other Brazilian states. In the present study molecular biology
      techniques were used for the detection and genomic characterization of measles
      viruses from clinical samples such as urine and nasopharyngeal secretions
      collected in the states of Rio de Janeiro, Minas Gerais and Parana, during the
      1997 epidemic. RT-PCR and nucleotide sequence analysis of part of the carboxyl
      terminal region of the nucleoprotein gene of measles viruses obtained directly
      from clinical samples or from infected cell cultures during this epidemic
      classified all as wild-type of genotype D6. As the genotype D6 was identified in
      different Brazilian states, this study demonstrated that this genotype was
      circulating in Brazil during the 1997 epidemic.

PMID- 11241462
TI  - Age- and dose-interval-dependent antibody responses to inactivated poliovirus
      vaccine.
AB  - Antibody responses were studied in five groups of children immunized with
      different three-dose schedules of inactivated poliovirus vaccine (IPV). The age
      of the child at the first dose (1-4 months) and the interval between the first
      and second doses (2-4 months) influenced the initial responses in a serotype
      dependent manner. All the groups attained sufficient antibody level after three
      doses but the third dose given at 18 months resulted in higher persisting
      antibody levels than that given at 12 months. The highest persisting antibody
      titers against PV1 and PV2 (but not against PV3) at the age of 3 years were
      measured in the control group immunized with the current schedule (P < 0.001) in
      which the first dose is given at 6 months. The level of maternal antibodies
      present at the time of the first dose correlated negatively with the antibody
      titers as late as at 3 years of age. It is concluded that three doses of IPV
      given in widely variable schedules may result in satisfactory immune responses in
      children but, for optimal results, very early onset of the program and short
      dosage intervals should be avoided.

PMID- 11241463
TI  - Genetic characterization of the rotaviruses associated with a nursery outbreak.
AB  - G1P[6] rotaviruses were demonstrated previously to be associated with the
      neonatal nursery outbreak of gastroenteritis in Changhua Christian Hospital that
      is located in the central region of Taiwan, from September 1994 to May 1995.
      Meanwhile, rotaviruses were detected in children hospitalized for acute
      gastroenteritis. Our study characterizes the rotaviruses associated with the
      nursery outbreak by using genetic approaches. Nucleotide sequence analysis
      revealed that the VP7 genes of the nursery rotaviruses were distinct from those
      of the strains circulating in the community. The G1P[6] rotaviruses recovered
      from the nursery were closely related to another neonatal G1P[6] strain from the
      northern region of Taiwan in both the VP4 and VP7 genes. The VP4 genes of these
      nursery strains differed from those of the P[6] human reference strains 1076,
      M37, RV3, and ST3. Apparently, these nursery rotaviruses were distinct from the
      strains circulating in the community and seemed to be a variant when compared
      with P[6] strains reported previously.

PMID- 11241464
TI  - Barth's syndrome-like disorder: a new phenotype with a maternally inherited
      A3243G substitution of mitochondrial DNA (MELAS mutation).
AB  - An Argentine male child died at 4.5 years of age of a lethal mitochondrial
      disease associated with a MELAS mutation and a Barth syndrome-like presentation.
      The child had severe failure to thrive from the early months and for
      approximately two years thereafter. In addition, the patient had severely delayed
      gross motor milestones, marked muscle weakness, and dilated cardiomyopathy that
      progressed to congestive heart failure. He also had persistently elevated urinary
      levels of 3-methylglutaconic and 2-ethylhydracrylic acids and low blood levels of
      cholesterol. Detailed histopathologic evaluation of the skeletal muscle biopsy
      showed high activity of succinate dehydrogenase, a generalized decrease of COX
      activity, and abundant ragged-red fibers. Electron microscopic studies revealed
      multiple mitochondrial abnormalities in lymphocytes and monocytes, in the
      striated muscle, and in the postmortem samples (muscle, heart, liver, and brain).
      Biochemical analysis showed a pronounced and constant lactic acidosis, and
      abnormal urinary organic acid excretion (unchanged in the fasting and
      postprandial states). In addition, in CSF there was a marked increase of lactate
      and beta-hydroxybutyrate (beta-HOB) and also a high systemic ratio beta
      HOB/acetoacetate. Enzymatic assay of the respiratory chain in biopsied muscle
      showed 10% of complex I activity and 24% of complex IV activity compared with
      controls. Molecular studies of the mitochondrial genome revealed an A to G
      mutation at nucleotide pair 3243 in mitochondrial DNA, a well-known pathogenetic
      mutation (MELAS mutation) in all the patient's tissues and also in the blood
      specimens of the probands mother and sibs (4 of 5). The diagnosis of MELAS
      mutation was reinforced by the absence of an identifiable mutation in the X
      linked G4.5 gene of the propositus. The present observation gives additional
      evidence of the variable clinical expression of mtDNA mutations in humans and
      demonstrates that all clinical variants deserve adequate investigation to
      establish a primary defect. It also suggests adding Barth-like syndrome to the
      list of phenotypes with the MELAS mutation.

PMID- 11241465
TI  - Interstitial deletion 4q32-34 with ulnar deficiency: 4q33 may be the critical
      region in 4q terminal deletion syndrome.
AB  - We report on an infant with Robin sequence; mild developmental delay; a left
      ulnar ray defect with absent ulna and associated metacarpals, carpals and
      phalanges; and a right ulnar nerve hypoplasia. He had a de novo interstitial
      deletion of 4q32-->q34. The critical region involved in the 4q terminal deletion
      syndrome may be 4q33. This conclusion was suggested by showing that
      del(4)(q31qter), del(4)(q32qter), and del(4)(q33qter) result in a similarly
      severe phenotype. In addition, we propose that genes for distal arm development,
      in particular for development of the left ulnar ray, central nervous system
      development, and cleft lip and palate, may be located at 4q33.

PMID- 11241466
TI  - Women's interest in genetic testing for breast cancer susceptibility may be based
      on unrealistic expectations.
AB  - We report on results of an interview study assessing women's attitudes toward and
      hypothetical interest in genetic susceptibility testing for breast cancer. Data
      are from 246 interviews with women of varying ethnicity (African American,
      European American, Native American, and Ashkenazi Jewish), family history of
      breast cancer (negative, positive, and borderline), and educational level.
      Semistructured interviews included questions on general health beliefs;
      attitudes, experiences, and concerns about breast cancer; and hypothetical
      interest in genetic testing. Influence of specific test characteristics was
      assessed with 14 Likert scales varying negative and positive predictive value,
      timing of disease, possible medical interventions following a positive result.
      Results reported include both statistical and qualitative analysis. We found that
      women had a high level of interest in testing which, in general, did not vary by
      ethnicity, level of education, or family history. Interest in testing appeared to
      be shaped by an exaggerated sense of vulnerability to breast cancer, limited
      knowledge about genetic susceptibility testing, and generally positive views
      about information provided through medical screening. However, study participants
      were most interested in a test that didn't exist (high positive predictive value
      followed by effective, noninvasive, preventive therapy) and least interested in
      the test that does exist (less than certain positive predictive value, low
      negative predictive value, and limited, invasive, and objectionable therapeutic
      options). Our data suggest that without a careful counseling process, women could
      easily be motivated toward interest in a test which will not lead to the disease
      prevention they are seeking.

PMID- 11241467
TI  - Functional disomy for Xq26.3-qter in a boy with an unbalanced
      t(X;21)(q26.3;p11.2) translocation.
AB  - A nine-month-old boy, with functional disomy for Xq26-qter and multiple
      congenital abnormalities, is reported. The boy had severe pre- and postnatal
      growth retardation, profound developmental delay, hypotonia, microcephaly,
      agenesis of the corpus callosum, dysmorphic facial features, cryptorchidism, and
      left multidysplastic kidney. He developed feeding difficulties and infantile
      spasms. G-banding analysis of his chromosomes showed additional material on the
      short arm of chromosome 21. His parents refused to submit to chromosome analysis.
      Analysis with chromosome microdissection followed by reverse and forward
      chromosome painting indicated his karyotype as 46,XY,der(21)t(X;21)(q26;p11.2).
      This is the first description of pure functional disomy for Xq26-qter due to an
      unbalanced X-autosome translocation.

PMID- 11241468
TI  - CHARGE association with choanal atresia and inner ear hypoplasia in a child with
      a de novo chromosome translocation t(2;7)(p14;q21.11).
AB  - A 3-year-old boy was diagnosed with CHARGE association on the basis of bilateral
      choanal atresia, absence of the semicircular canals, hypoplastic cochleae,
      genital hypoplasia, growth and developmental delays, cranial nerve dysfunction,
      and facial anomalies. Ophthalmologic and cardiac evaluations were normal. He was
      found to have an apparently balanced t(2;7)(p14;q21.11) chromosomal
      translocation. Parental karyotypes were normal. Although there is evidence
      suggesting a genetic basis for CHARGE association, individuals with chromosomal
      abnormalities and CHARGE are rare. In the described patient, the presence of
      characteristic CHARGE features suggests that the t(2;7)(p14;q21.11) translocation
      breakpoints may cause a deletion or disruption of genes within the involved
      regions that are involved in the generation of the CHARGE association phenotype.

PMID- 11241469
TI  - A recognizable syndrome within CHARGE association: Hall-Hittner syndrome.

PMID- 11241470
TI  - Temporal bone anomaly proposed as a major criteria for diagnosis of CHARGE
      syndrome.
AB  - The acronym CHARGE defines a non-random clustering of congenital malformations of
      unknown origin. Classical diagnostic criteria include: 1) one major feature
      namely coloboma/microphthalmia or choanal atresia, and 2) four of the six
      features designated in the CHARGE acronym. Interestingly, all CHARGE patients
      hitherto reported had partial or complete semicircular canal hypoplasia on
      temporal bone CT-scan. We report on semicircular canal agenesis/hypoplasia in
      three patients with three to four features of the CHARGE syndrome and neither
      coloboma nor choanal atresia and we propose to include temporal bone
      malformations as a major criteria for diagnosis of CHARGE syndrome.

PMID- 11241471
TI  - Long-term treatment with growth hormone improves final height in a patient with
      Pallister-Hall syndrome.
AB  - Pallister-Hall syndrome is a disorder of development consisting of hypothalamic
      hamartoma, pituitary dysfunction, central polydactyly and visceral malformations.
      This disorder is inherited as an autosomal dominant trait and is caused by
      mutations of the GLI3 gene encoding a zinc finger transcription factor. We
      describe a case of Pallister-Hall syndrome with growth hormone neurosecretory
      dysfunction, successfully treated with growth hormone until attainment of final
      height. We conclude that children with Pallister-Hall syndrome and short stature
      be evaluated carefully for spontaneous somatotropic function and, if necessary,
      treated with growth hormone.

PMID- 11241472
TI  - Mazabraud syndrome in two patients: clinical overlap with McCune-Albright
      syndrome.
AB  - Mazabraud syndrome is a rare sporadic disorder, mainly characterized by bone
      fibrous dysplasia and intramuscular myxomas. We report here two new cases of
      Mazabraud syndrome. One of our patients (Patient 1) also had cafe-au-lait spots
      and multinodular goiter suggestive of McCune-Albright syndrome. We review the 37
      previously reported cases with Mazabraud syndrome and discuss the 6/37 patients
      with criteria of Mazabraud and McCune-Albright syndromes. Based on the clinical
      overlap between the two syndromes, we tested the GNAS1 gene in blood leukocytes
      and skin fibroblasts of Patient 1, but found no evidence of an activating
      mutation in the GNAS1 gene.

PMID- 11241474
TI  - Heterotaxia as an outcome of maternal diabetes: an epidemiological study.
AB  - There are very few publications on the possible relationship between maternal
      diabetes and infants presenting heterotaxia-asymmetry defects. In mice, there is
      a relationship between maternal diabetes and heterotaxia, although this is
      influenced by the fetal genotype. An epidemiological analysis of heterotaxia
      asymmetry in children born to diabetic mothers (diabetes mellitus or gestational
      diabetes) is presented here. The analysis is based in the case-control study of
      the ECEMC database. However, due to the very small sample size for each type of
      study of heterotaxia-asymmetry alterations, up to 10 control infants for each
      case were selected. Although the sample size is small, the results suggest that
      only maternal diabetes mellitus significantly increases the risk for
      transposition of great vessels (OR=61.87; CI:7.36-519.82), and transposition of
      viscera (OR=24.82; CI;1.84-335.44).

PMID- 11241473
TI  - Renal-coloboma syndrome: prenatal detection and clinical spectrum in a large
      family.
AB  - Renal-coloboma syndrome includes abnormalities in the urogenital and ocular
      systems as its primary manifestations, although it can be associated with
      abnormalities in other systems as well. This syndrome is caused by mutations in
      the PAX2 gene and is transmitted as an autosomal dominant trait. We report a
      family in which at least 7 members have manifestations of renal-coloboma
      syndrome, including two in whom renal disease was diagnosed prenatally by
      ultrasound examination. A pathogenic frame-shift mutation (619insG) was found in
      the PAX2 gene in affected family members, who show remarkable variability in both
      the ocular and renal manifestations of the syndrome.

PMID- 11241475
TI  - Glucocerebrosidase mutations among African-American patients with type 1 Gaucher
      disease.
AB  - While the inherited deficiency of the enzyme glucocerebrosidase (Gaucher disease)
      is panethnic in its distribution, there have not been studies of the mutations
      encountered in specific ethnic groups in the United States, other than those on
      Ashkenazi Jews. We present the clinical descriptions and genotypes of seven
      patients of African-American ancestry with type 1 Gaucher disease, and summarize
      the published literature regarding the genotypes encountered in this population.
      All seven of the patients had moderate-to-severe manifestations of the disease,
      and all developed symptoms by adolescence. Genotypic analyses revealed that no
      two probands shared the same genotype. The common mutations N370S, c.84-85insG,
      IVS2+1 G-->A, and R463C were not seen. Mutation L444P was present on one allele
      in each of the patients; but the same mutation was encountered as a single point
      mutation in three of the patients, and as part of a recombinant allele in four of
      the patients. Southern blot analyses revealed a glucocerebrosidase fusion allele
      in one patient, and a duplication resulting from recombination in the region
      downstream from the glucocerebrosidase gene in three of the patients. Five
      different point mutations (A90T, R48W, N117D, R170C, and V352L), one deletion
      mutation (c.222-224 delTAC), and one insertion mutation (c.153-154 insTACAGC)
      were encountered. Our results demonstrate that there is significant genotypic
      heterogeneity among African-American patients with type 1 Gaucher disease, and
      that recombinations in the glucocerebrosidase gene locus are particularly common
      in this patient group. Published 2001 Wiley-Liss, Inc.

PMID- 11241476
TI  - Trisomy 1 in a clinically recognized IVF pregnancy.
AB  - Most chromosomal trisomies lead to spontaneous abortion. To date, trisomies of
      all human chromosomes have been observed. Chromosome 1 has been the most elusive,
      as trisomy 1 was the last aberration to be identified. To date there has been
      only one case report of a full trisomy 1 in the literature [1997: Am J Med Genet
      68:98]. We have identified a second full trisomy 1 from the chromosome analysis
      of products of conception. We present a patient who conceived by in vitro
      fertilization (IVF). The cellular divisions of the fertilized egg were carefully
      monitored prior to transfer. Hormonal changes (increased hCG) indicated that
      implantation had occurred. Vaginal ultrasound demonstrated a gestational sac. At
      42 days postfertilization no fetal heart beat could be detected. Cytogenetic
      analysis of the chorionic villi isolated from the products of conception found
      that all of the cells analyzed contained a 47,XY,+1 chromosomal complement.

PMID- 11241477
TI  - Bi-iliac distance and iliac bone position compared to the vertebral column in
      normal fetal development.
AB  - Prenatal standards of bi-iliac width were not found in the literature based on
      autopsy investigations, nor was the caudo-cranial position of the ilia compared
      to the vertebral column. The first purpose of the present study was to establish
      normal standard values for the bi-iliac distance in fetal life, the second to
      evaluate the level of the iliac bones proportional to the ossified vertebral
      column. Whole body radiographs in antero-posterior projections from 98 human
      fetuses (36 female and 44 male fetuses, as well as 18 fetuses on which the sex
      had not been determined) were analyzed in the study. The fetuses derived from
      spontaneous or induced abortions and they were radiographed as part of the
      required autopsy procedure. The crown-rump-length (CRL) of the fetuses varied
      from 32 to 245 mm. The outer and inner bi-iliac distance was measured from the
      radiographs with a digital Helios slide caliper. The caudo-cranial position of
      the iliac bones was evaluated. The present study shows that in normal fetal
      development there is a continuous linear enlargement of the pelvic region in the
      transverse and vertical planes. The upper iliac contour stays at the level of the
      first sacral vertebral body, whereas the lower iliac line moves caudally.
      Significant differences between male and female fetuses were not found. The value
      of the present study is that the results can be used as reference standards in
      prenatal pathology.

PMID- 11241478
TI  - Isolated glycerol kinase deficiency and Fanconi anemia.

PMID- 11241479
TI  - Two novel CLN2 gene mutations in a Chinese patient with classical late-infantile
      neuronal ceroid lipofuscinosis.

PMID- 11241480
TI  - Congenital insensitivity to pain with anhidrosis: an NGF/TrkA-related disorder.

PMID- 11241482
TI  - No evidence of unbalanced growth-related gene inheritance in a series of
      overgrowth syndrome patients.

PMID- 11241483
TI  - Reduced ovarian complement, premature ovarian failure, and Down syndrome.

PMID- 11241485
TI  - Dr. Ram Verma, cytogeneticist 1946-2000.

PMID- 11241484
TI  - Incontinentia pigmenti in a surviving male is accompanied by hypohidrotic
      ectodermal dysplasia and recurrent infection.
AB  - Familial Incontinentia pigmenti (IP) is a rare X-linked dominant condition. The
      affected cases have characteristic skin lesions, hair, eye, teeth and nail
      abnormalities and may also have neurological problems. The diagnosis has
      traditionally been made on clinical grounds. Segregation analysis has suggested
      that it is lethal in males. Only one liveborn male has been reported who died at
      one day of age. Female cases of IP survive because of the moderating effects of
      Lyonization. This child was the affected son of a female with IP. He had a novel
      phenotype consistent with hypohidrotic ectodermal dysplasia with immune
      deficiency (HED-ID) but with additional features: he had major problems with
      hematological disturbances, failure to thrive due to malabsorption, recurrent
      infections, generalized osteosclerosis and lymphedema of his lower limbs. He also
      demonstrated some typical features of IP with a generalized reticular skin
      hyperpigmentation, sparse hair and delayed eruption of teeth. The gene for NEMO
      (NF-kappa B Essential Modulator) has recently been shown to be mutated in cases
      of IP. Furthermore, most (80%) of patients possess a recurrent genomic
      rearrangement that deletes part of the gene resulting in an inactive NEMO
      protein. In the male case described here, a NEMO stop codon mutation has been
      identified that has arisen de novo in his affected mother. This mutation is
      likely to have a less severe effect on NEMO activity and may explain why this
      child survived for two years and 7 months.

PMID- 11241486
TI  - Non-bullous ichthyosiform erythroderma associated with retinitis pigmentosa.
AB  - Non-bullous ichthyosiform erythroderma (NBIE) is an autosomal recessive condition
      characterized by generalized erythema and scaling. Two brothers with NBIE and
      retinitis pigmentosa are reported. One of them also had a marfanoid habitus,
      thoracic kyphosis, and arachnodactyly, and was heterozygous for alpha 1
      antitrypsin deficiency. A third brother had skin involvement, but normal vision.
      Retinitis pigmentosa has been described in association with NBIE as part of Rud
      syndrome, which is no longer considered a separate entity. Major diagnostic
      features of Rud syndrome, such as hypogonadism, mental retardation, and epilepsy
      were absent in this family. The association of NBIE with retinitis pigmentosa in
      this family seems distinct from any previously described, currently recognized
      syndrome.

PMID- 11241487
TI  - Confirmation of the autosomal recessive syndrome of ectopia lentis and
      distinctive craniofacial appearance.
AB  - We report four members of a Lebanese Druze family with the syndrome of lens
      dislocation, spontaneous filtering blebs, anterior segment abnormalities, and a
      distinctive facial appearance. The constellation of clinical abnormalities in
      these patients is not suggestive of the Marfan syndrome or other connective
      tissue disorders associated with ectopia lentis. We previously described this
      syndrome in another presumably unrelated and highly inbred Druze family from the
      mountains of Lebanon. We postulated autosomal recessive inheritance in a pseudo
      dominant pedigree. A few isolated reports of similar cases are scattered in the
      world literature. We now confirm that this is a distinct autosomal recessive
      syndrome whose gene mutation is enriched in the Lebanese Druze community.

PMID- 11241488
TI  - Severe arterial occlusive disorder and brachysyndactyly in a boy: a further case
      of Grange syndrome?
AB  - We report on a 15-year-old boy with stenosis and occlusion of multiple cranial,
      renal, and celiac arteries, aneurysm of the basilar artery, bilateral cutaneous
      syndactyly between fingers IV-V, partial cutaneous syndactyly between fingers III
      IV on the right hand, brachydactyly, and borderline mental retardation. The
      clinical course was characterized by recurrent abdominal pain, gastritis, and
      high blood pressure. The pattern of the clinical and radiological findings is
      different from fibromuscular dysplasia (FMD) and Moyamoya disease, and highly
      suggestive of a syndrome described by Grange in four siblings (MIM#602531) Grange
      et al. [1998: Am J Med Genet 75: 469-480].

PMID- 11241489
TI  - Isochromosome consisting of terminal short arm and proximal long arm X in a girl
      with short stature.
AB  - A 16-year-old girl with short stature, short neck, shield chest, and cubitus
      valgus was studied. FISH analyses of her structurally altered X chromosome showed
      a der(X)- (wcpX+,TelXp/Yp++,SHOX++,STS++,KAL-, 37A12-,DXZ1+,XIST++,97L7++,300O13
      ,404F- 18-,417G15-,404F18-,140A-,TelXq/Yq-). These results, together with the
      high-resolution banding analysis, indicated her karyotype to be 46,X,der(X)(Xpter
      ->Xp22.3::Xq22.3--> cen-->Xq22.3::Xp22.3-->Xpter). The der(X) was an
      isochromosome, consisting of duplicated terminal short arms and duplicated
      proximal long arms. This in turn suggested that the chromosome was formed through
      pericentric inversion of an X chromosome, followed by isochromosome formation
      through sister chromatid exchange at Xp, close to the centromere. Replication R
      banding analysis showed that the abnormal X chromosome was late replicating.
      Analysis of digestion patterns with a methylation-sensitive restriction
      endonuclease of the phosphoglycerate kinase 1 gene, located in Xq13.3, indicated
      that its inactivation patterns were completely skewed.

PMID- 11241490
TI  - Oculo-palatal-cerebral syndrome: a second case.
AB  - Oculo-palato-cerebral syndrome is an extremely rare disorder consisting of low
      birth weight, microcephaly, short stature, persistent hyperplastic primary
      vitreous, microphthalmia, large ears, small hands and feet, cleft palate, joint
      hypermobility, developmental delay, and cerebral atrophy. There has been one
      report of a consanguineous family with three affected children, suggesting
      autosomal recessive inheritance. We report on the second case of this disorder.
      Our patient, a 2-year-old boy, had growth delay, microcephaly, bilateral
      persistent hyperplastic primary vitreous with right microphthalmia, long ears
      with thickened helices, small hands and feet, highly arched palate, joint
      hypermobility, hypoplastic nails, frontal cerebral atrophy and thinning of the
      corpus callosum on brain magnetic resonance imaging, and mild developmental
      delay. He has much milder features than those seen in the previously reported
      cases.

PMID- 11241491
TI  - Clinical and genetic characterization of an autosomal dominant nephropathy.
AB  - Autosomal dominant familial nephropathies with adult onset, no macroscopic cysts,
      and progressive deterioration include medullary cystic disease (ADMCKD) as well
      as other less specific entities. We studied a kindred of Jewish ancestry in which
      15 members (both male and female) have suffered from chronic renal failure. The
      first evidence of renal involvement was observed between 18 and 38 years. It
      included hypertension followed by progressive renal insufficiency. No polyuria,
      anemia, gout, hematuria, nor proteinuria were seen. An average of 4.5 years
      elapsed from diagnosis to end-stage renal disease. Renal pathology at early
      stages of the disease showed extensive tubulointerstitial fibrosis and global
      glomerulosclerosis. Linkage analysis was performed at the two known loci of
      ADMCKD, on Chromosomes 1 and 16. Linkage to the chromosome 16 locus was excluded.
      However, linkage to the chromosome 1q21 locus of ADMCKD was established with a
      maximum two-point LOD score of 3.82 to D1S394. The disease interval could be
      narrowed to about 9 cM/7.4 Mb between D1S1156 and D1S2635. Multiple-point linkage
      analysis revealed a maximum LOD of 4.21, with a broad peak from markers D1S2858
      and D1S2624. This report establishes linkage between a familial nephropathy
      characterized by hypertension and progressive renal failure to the locus
      described for ADMCKD, a disease classically associated with macroscopic
      corticomedullary cysts, salt-losing tubulointerstitial nephropathy, and anemia.
      This finding broadens the clinical spectrum of ADMCKD positioned on chromosome
      1q21 locus.

PMID- 11241492
TI  - Trisomy 20 mosaicism in two unrelated girls with skin hypopigmentation and normal
      intellectual development.
AB  - The prenatal diagnosis of trisomy 20 mosaicism presents a challenge for
      practitioners and parents. The diagnosis implies an uncertain risk for an
      inconsistent set of physical and developmental findings, as well as a substantial
      chance for a child that is normal physically and developmentally. We report two
      girls (ages nine years one month and eight years one month) with normal
      intelligence and hypopigmented skin areas. Both girls were born after a prenatal
      diagnosis of trisomy 20 mosaicism in amniocytes. Case 1 had 83% and 57% trisomy
      20 cells from two separate amniocenteses and Case 2 had 90% trisomy 20 cells from
      an amniocentesis. Trisomy 20 was confirmed after birth in urinary sediment (25%)
      and chorionic villus cells (15%) in Case 1, while cord blood lymphocytes (30
      cells) and skin fibroblasts (50 cells) had only 46,XX cells. Trisomy 20 was
      confirmed after birth in urinary sediment (100%), placenta (100%), cord (10%),
      amniotic membrane (50%), and skin fibroblasts (30%) in Case 2, while cord blood
      lymphocytes (100 cells) had only 46,XX cells. This is the first report of a
      hypopigmented pigmentary dysplasia associated with isolated trisomy 20 mosaicism.
      Our patients are the oldest reported children with trisomy 20 mosaicism confirmed
      after birth.

PMID- 11241494
TI  - Detailed characterization of 12 supernumerary ring chromosomes using micro-FISH
      and search for uniparental disomy.
AB  - Twelve patients with varying degrees of mosaicism for a supernumerary ring
      chromosome were studied. The ring chromosomes were characterized using
      microdissection in combination with degenerate nucleotide-primed polymerase chain
      reaction (PCR) and reverse painting (micro-FISH). This method made it possible to
      determine the chromosomal origin of the ring chromosomes in detail, and thus to
      compare the phenotypes of similar cases. Eleven of the marker chromosomes were
      derived from the most proximal part of 1p, 3p, 3q, 5p, 7q, 8p, 8q, 9p, 10p and
      20p. One marker chromosome had a complex origin, including the proximal and the
      most distal part of 20q. Eight of the families were also investigated for
      uniparental disomy (UPD) using microsatellite analysis. One case with maternal
      UPD 9 was found in a child with a ring chromosome derived from chromosome 9,
      r(9)(p10p12).

PMID- 11241493
TI  - ATP7A gene mutations in 16 patients with Menkes disease and a patient with
      occipital horn syndrome.
AB  - Genomic DNA of 17 unrelated Japanese males with Menkes disease and 2 Japanese
      males with occipital horn syndrome were studied for mutations in the ATP7A gene.
      Using SSCP analysis and direct sequencing of the exons and the 5'-upstream region
      of the gene amplified by PCR, we identified 16 mutations in 16 of 17 males with
      Menkes disease, including 4 deletions, 2 insertions, 6 nonsense mutations, 2
      missense mutations, and 2 splice-site mutations. All these mutations were those
      that affect the function of the gene. Of the two males with occipital horn
      syndrome, one had a splice-site mutation in intron 6 that led to normal-size and
      smaller-size transcripts. The amount of the normal-size transcripts in his
      cultured skin fibroblasts was 19% of the normal level. His serum copper and
      ceruloplasmin levels were normal, whereas his cultured skin fibroblasts contained
      increased levels of copper. These findings indicate that his mild clinical
      manifestations were due to the presence of normal-size and presumably functional
      transcripts of the gene. DNA sequencing analysis of the exons and 5'-upstream
      region of the ATP7A gene in 20 normal individuals and the 19 affected males
      identified 25 polymorphisms.

PMID- 11241495
TI  - Maternal germinal mosaicism of X-linked agammaglobulinemia.
AB  - X-linked agammaglobulinemia (XLA) is an immunodeficiency caused by abnormalities
      in tyrosine kinase (BTK), and is characterized by a deficiency of peripheral
      blood B cells. We studied cytoplasmic expression of BTK protein and analyzed the
      BTK gene (BTK) in peripheral blood mononuclear cells from two siblings with XLA
      and additional family members. Cytoplasmic expression of BTK protein in monocytes
      was not detected in either patient with XLA. A single base deletion (C563) in BTK
      exon 6, which encodes the TH domain, was identified in both XLA patients.
      However, normal cytoplasmic expression of BTK protein in monocytes was detected
      in their mother without any BTK mutation. These results strongly suggest germinal
      mosaicism in the mother.

PMID- 11241496
TI  - Calvarial "doughnut lesions": clinical spectrum of the syndrome, report on a
      case, and review of the literature.
AB  - Many pathologic fractures, lumps on the head, elevated serum alkaline phosphatase
      (ALP) levels, and dental caries are the main characteristics of the rare
      autosomal dominantly inherited calvarial "doughnut lesions" (MIM 126550). We
      report the sporadic case of a 16-year-old patient who has had 10 pathologic
      fractures between age 6 weeks and 15 years. An elevated serum ALP level was found
      at age 11 and skull lumps at age 15; radiography showed frontal and parietal
      round radiolucencies surrounded by sclerotic bone comparable to doughnuts.
      Magnetic resonance imaging (MRI) showed skull lesions at an early stage. Because
      the findings are reminiscent of osteogenesis imperfecta (OI), collagen types I,
      III, and V were analyzed in fibroblasts and shown to be normal in terms of
      quantities, proportions, electrophoretic mobility, and thermostability. Thus,
      this rare syndrome can be distinguished from OI by collagen analysis and MRI of
      the skull at an early stage, even before palpable skull lesions appear.

PMID- 11241497
TI  - Clinical expression and SRY gene analysis in XY subjects lacking gonadal tissue.
AB  - In several syndromes genetic males lack gonadal tissue. A range of phenotypes are
      seen, which varies from complete female external genitalia to anorchic subjects
      with sexual infantilism. Differences in phenotypic expression depend on the stage
      at which testes degenerated during intrauterine development. Although most cases
      of these syndromes are sporadic, several instances of familial recurrence suggest
      a genetic origin. To help elucidate the source, we performed molecular analysis
      of the complete SRY gene open reading frame in two subjects with true agonadism
      and in two with anorchia. Our results add to previous findings indicating that
      molecular defects in SRY are not readily identified as a cause of these
      syndromes.

PMID- 11241498
TI  - Syndrome of short stature, widow's peak, ptosis, posteriorly angulated ears, and
      joint problems: exclusion of the Aarskog (FGD1) gene as a candidate gene.
AB  - A syndrome encompassing postnatal onset of short stature, widow's peak, ptosis,
      posteriorly angulated ears, and limitation of forearm supination is reported in a
      boy and his mother. The boy has not yet experienced dislocation of patella or
      other joint anomaly except for limitation of supination of the forearms. On the
      other hand, the mother has a milder limitation of supination only on the left arm
      and is devoid of ptosis. Their condition is reminiscent of that described in the
      family reported by Kapur et al. [1989: Am. J. Med. Genet. 33: 357-363.], which
      showed an X-linked dominant mode of inheritance. DNA study on our family using an
      intragenic polymorphism of the Aarskog syndrome (FGD1) gene and four other
      adjacent markers convincingly excludes the possibility that their condition could
      be caused by a mutation of the FGD1 gene. Our family and the family reported by
      Kapur et al. may suggest segregation of a novel X-linked dominant condition.

PMID- 11241500
TI  - No cholesterol metabolism anomalies detectable in infants with hypertrophic
      pyloric stenosis.

PMID- 11241499
TI  - Weaver syndrome with neuroblastoma and cardiovascular anomalies.
AB  - We report on an infant with Weaver syndrome, neoplasia and cardiovascular
      anomalies. Stage 4S neuroblastoma underwent spontaneous resolution. Three
      neoplasms have been reported in Weaver syndrome: another stage 4S neuroblastoma
      [Muhonen and Menezes, 1990: J Pediatr 116:596-599], an ovarian endodermal sinus
      tumor [Derry et al., 1999: J Med Genet 36:725-728], and a sacrococcygeal teratoma
      [Kelly et al., 2000: Am J Med Genet 95:492-495]. No case was associated with
      cardiovascular anomalies. Our patient had VSD and PDA, and although several other
      patients with Weaver syndrome have had cardiovascular anomalies, they were shown
      not to have neoplasia.

PMID- 11241501
TI  - Trisomy 1q42qter "syndrome": additional case report.

PMID- 11241502
TI  - A brief history of numbers and statistics with cytometric applications.
AB  - A brief history of numbers and statistics traces the development of numbers from
      prehistory to completion of our current system of numeration with the
      introduction of the decimal fraction by Viete, Stevin, Burgi, and Galileo at the
      turn of the 16th century. This was followed by the development of what we now
      know as probability theory by Pascal, Fermat, and Huygens in the mid-17th century
      which arose in connection with questions in gambling with dice and can be
      regarded as the origin of statistics. The three main probability distributions on
      which statistics depend were introduced and/or formalized between the mid-17th
      and early 19th centuries: the binomial distribution by Pascal; the normal
      distribution by de Moivre, Gauss, and Laplace, and the Poisson distribution by
      Poisson. The formal discipline of statistics commenced with the works of Pearson,
      Yule, and Gosset at the turn of the 19th century when the first statistical tests
      were introduced. Elementary descriptions of the statistical tests most likely to
      be used in conjunction with cytometric data are given and it is shown how these
      can be applied to the analysis of difficult immunofluorescence distributions when
      there is overlap between the labeled and unlabeled cell populations.

PMID- 11241503
TI  - Optimal number of reagents required to evaluate hematolymphoid neoplasias:
      results of an international consensus meeting.
AB  - At the ISAC 2000 Congress, the Clinical Cytometry Society organized a meeting of
      international experts to reach consensus on the minimum number of antibodies
      required for a full evaluation of hematologic and lymphoid neoplasias. A
      questionnaire was distributed prior to the meeting to numerous experts from US
      and European institutions and 13 responses were received. At the meeting, 25
      individuals, including most of those who returned responses, participated in the
      discussions and voted on the issues presented. In chronic lymphoproliferative
      disorders (CLD), 9 antibodies (anti-CD5, CD19, kappa, lambda, CD3, CD20, CD23,
      CD10, and CD45) were deemed essential for initial evaluation by 75% of the
      participants. There was near unanimity that additional markers (selected from
      CD22, FMC7, CD11c, CD103, CD38, CD25, CD79b and heavy chains for B-cell
      disorders, and CD4, CD7, CD8, CD2, CD56, CD16, TCRa/b, and TCRg/d for T-cell
      disorders) would be needed to fully characterize CLD, although not every marker
      would be useful in all cases. Tissue lymphomas were believed to be similar to
      CLD, needing a minimum of 12--16 markers. However, for some cases, CD30, bcl-2,
      TdT, CD71, CD1a, and CD34 were cited as useful by the participants. Markers
      mentioned for plasma cell disorders included kappa, lambda, CD38, CD45, CD56,
      CD19, CD20, CD138, and heavy chains. Of 17 voting participants, 16 agreed that
      between 5 to 8 markers would be essential reagents for plasma cell disorders. For
      acute leukemia (AL), 10 markers (CD10, CD19, CD13, CD33, CD34, CD45, CD7, CD14,
      CD3, and HLADR) were considered essential by 75% of participants for initial
      characterization of the leukemia lineage. Most (>75%) agreed that at least one
      more B (CD20, CD22, CD79a, IgM), T (CD1a, CD2, CD4, CD5, CD8), myeloid (CD11b,
      CD15, CD64, CD117, myeloperoxidase), erythroid (CD36, CD71, glycophorin A), and
      megakaryocytic (CD41, CD61) reagents should be included in the essential panel.
      However, there was no agreement as to which was optimal. Thus, approximately 13-
      15 of those reagents would be considered essential in all cases of AL, whereas
      others (CD16, CD56, CDw65, TdT, and cytoplasmic CD3) were mentioned as useful in
      some cases. Almost all voting participants believed that the appropriate number
      of markers for complete characterization of AL would average 20--24. The majority
      of the responders (11 of 13) indicated that fewer reagents could be used in
      monitoring or staging patients with previously characterized disease, but not all
      ventured a specific number of reagents. From the above results, we conclude that
      the phenotypic analysis of hematologic and lymphoid neoplasia requires a rather
      extensive panel of reagents. Supplementary reagents might even be necessary if
      they prove to become relevant for diagnostic purposes. Reducing the number of
      antibodies could significantly compromise the diagnostic accuracy, appropriate
      monitoring, or therapy of these disorders.

PMID- 11241504
TI  - Apoptotic index by Annexin V flow cytometry: adjunct to morphologic and
      cytogenetic diagnosis of myelodysplastic syndromes.
AB  - The myelodysplastic syndromes (MDS) are clonal hematologic malignancies
      characterized by pancytopenia, dysplastic hematopoiesis, and a propensity to
      leukemic transformation. Increased apoptosis has been noted in MDS as a possible
      explanation for ineffective hematopoiesis, with lower levels in progression to
      and in de novo acute leukemia. Apoptosis can be measured by binding of Annexin V
      to exposed membrane phosphatidylserine. We postulated that the apoptotic index
      would aid in the differential diagnosis of MDS versus other hematopoietic
      diseases. We examined 33 bone marrow aspirates suspected of hematopoietic
      malignancy for apoptotic index by Annexin V analysis using a Becton Dickinson
      FACStar+ flow cytometer. The apoptotic index was expressed as the percentage of
      Annexin V-positive cells divided by total mononuclear cells in the gate. By
      standard morphologic analysis, 16 cases were diagnosed as MDS (9 refractory
      anemia [RA], 2 refractory anemia with ringed sideroblasts [RARS], 1 refractory
      anemia with excess of blasts [RAEB], 3 chronic myelomonocytic leukemia [CMML],
      and 1 unclassified), 11 as acute leukemia (AL), 6 as myeloproliferative disorders
      (MPD). Eight cases (uninvolved marrow of five patients with lymphoproliferative
      disorders [LPD], one patient with multiple myeloma, and two patients with anemia
      of chronic disease) served as nonneoplastic controls. A higher degree of
      apoptosis was observed in MDS (mean = 44.7%; range = 29.5--60%) compared with MPD
      (mean = 8.2%; range = 2.3--15.4%), AL (mean = 16.1%; range = 5.1--29.4%), and
      control marrow samples (mean = 11.6%; range = 1.5--21%). Additionally, the
      apoptotic index was significantly higher in MDS compared with MPD (P < 0.0001).
      In conclusion, a high apoptotic index occurs in MDS, supporting previous reports
      and suggesting that Annexin V analysis can be used as an adjunct in the diagnosis
      of MDS versus MPD. This would be particularly useful for the often-difficult
      distinction between early MDS and early MPD cases with equivocal morphology.

PMID- 11241506
TI  - Low degree of activation of circulating neutrophils determined by flow cytometry
      during cardiac surgery with cardiopulmonary bypass.
AB  - BACKGROUND: Enhanced expression of adhesion molecules LFA-1 (CD11a/CD18) and Mac
      1 (CD11b/CD18) following cardiac surgery with cardiopulmonary bypass (CPB) is
      held responsible for postoperative complications. Surface expression of these
      molecules, intracellular pH (pH(i)), and oxidative burst capacity was analyzed to
      test for neutrophil activation during pediatric cardiac surgery. METHODS: Blood
      samples were drawn from 36 patients (age: 3--16 years) 24 h preoperatively, after
      onset of anesthesia, after connection to CPB (CPB1, before and after passing CPB,
      n = 15), at reperfusion (CPB2), and up to 7 days postoperatively. Cells adhering
      to CPB filters were isolated (n = 11). Antigen expression, pH(i), and oxidative
      burst capacity on neutrophils was analyzed by flow cytometry. RESULTS: During
      surgery, oxidative burst capacity was at low level with a mild increase only 1
      day after surgery. pH(i) was decreased throughout the surgery. Surgery induced
      more than 36% decrease of LFA-1 and Mac-1 expression (P < 0.03). Up to
      postoperative day 7, no increase of antigen expression above baseline was found.
      Neutrophils isolated from filters of the CPB had increased LFA-1 and Mac-1
      expression (all P < 0.05). Integrin expression on neutrophils passing the CPB at
      CPB1 was decreased (P < 0.05). CONCLUSION: Reduced adhesion molecule expression
      on neutrophils may be due to selective filtration of highly adhesive cells. This,
      in combination with low-level oxidative burst capacity, induced by
      immunosuppressive cytokines (e.g., interleukin-10), reduced the neutrophil
      activity. Our data indicate that increased activity of circulating neutrophils
      cannot exclusively be held responsible for postoperative complications after
      surgery with CPB.

PMID- 11241505
TI  - Flow cytometric analysis of cytokine production by normal human peripheral blood
      dendritic cells and monocytes: comparative analysis of different stimuli,
      secretion-blocking agents and incubation periods.
AB  - In this paper, we comparatively analyze the effects of the following different
      stimuli on the production and intracellular accumulation of the interleukin (IL)
      1 beta, IL-6, IL-12, tumor necrosis factor-alpha (TNF-alpha), and IL-8
      inflammatory cytokines in both normal human peripheral blood (PB) dendritic cell
      (DC) subsets and monocytes: lipopolysaccharide (LPS) versus Staphylococcus aureus
      cowan I (SAC) in the presence or absence of interferon-(IFN)-gamma-, cytokine
      secretion-blocking agents (brefeldin A alone versus brefeldin A plus monensin),
      and incubation periods (6, 12, and 24 h). For this purpose, a four-color multiple
      staining direct immunofluorescence technique analyzed by flow cytometry was
      systematically used in all experiments (n = 19). Our results show that after
      stimulation, an important proportion of each of the two CD33(+) myeloid DC
      subsets as well as the monocytes produce significant amounts of all cytokines
      analyzed under each of the experimental conditions assayed. In contrast, CD33(
      /+lo) lymphoplasmocytoid DC failed to produce detectable levels of any of the
      above-mentioned cytokines under the same stimulatory conditions. Upon comparing
      the different stimuli used, LPS was associated with higher percentages of
      cytokine-producing cells compared with SAC, especially within the CD33(hi) DC
      subset; interestingly, the addition of IFN-gamma enhanced the response of
      monocytes to both LPS and SAC. As regards the secretion-blocking agents,
      brefeldin A alone was superior to the combination of brefeldin A and monensin.
      This is because it was frequently associated with both a higher percentage of
      cytokine-positive cells and greater amounts of detectable cytokines per cell.
      Sequential analysis of cytokine production by PB DC and monocytes after 6, 12,
      and 24 h of cell culture showed that after 6 h, an increased cell death rate
      existed among DC, which became even undetectable at 24 h, in the absence of a
      significant increase in cytokine secretion. In summary, our results show that
      from the experimental conditions assayed in this paper, to induce cytokine
      production by normal human DC and monocytes, maximum response is obtained once PB
      samples are stimulated for 6 h with LPS (with or without IFN-gamma) in the
      presence of brefeldin A alone.

PMID- 11241508
TI  - Preferential loss of 5q14-21 in intestinal-type gastric cancer with DNA
      aneuploidy.
AB  - BACKGROUND: Little is known about the genetic changes associated with DNA ploidy
      in gastric cancer (GC). The aim of this study was to identify recurrent or
      specific chromosomal regions of DNA sequence copy number aberrations (DSCNAs)
      that might harbor genes associated with DNA aneuploidy in GC. METHODS: We
      analyzed DSCNAs with comparative genomic hybridization and DNA ploidy by laser
      scanning cytometry in 16 primary intestinal-type GCs. RESULTS: All GCs examined
      showed at least one DSCNA (loss or gain); eight were DNA diploid (DD) tumors and
      eight were DNA aneuploid (DA) tumors. The frequent (>30%) DSCNAs were loss of
      5q14-21 and gains of 7p11-14, 8q, 20q, and Xq25-26. Recurrent amplifications
      (>10%) were detected at chromosomal regions 6p, 7p, and 13q. The overall number
      of DSCNAs was significantly greater in DA than in DD tumors (P = 0.006).
      Furthermore, the number of aberrations was clearly greater with 5q loss than
      without 5q loss (P = 0.002). Losses of 5q14-21, 9p21-pter, 16q, and 18q21-qter
      were preferentially detected in DA tumors. CONCLUSION: The present observations
      indicate that there is a close relationship between DSCNA and DNA ploidy in
      intestinal-type GC and that gene(s) at 5q14-21, 9p21-pter, 16q, and/or 18q21-qter
      may play important roles in acquisition of DNA aneuploidy.

PMID- 11241507
TI  - Clone heterogeneity in diploid and aneuploid breast carcinomas as detected by
      FISH.
AB  - We investigated the relationship between DNA ploidy and alterations in
      chromosomes 1, 8, 12, 16, 17, and 18 in 63 breast carcinoma samples by static
      cytofluorometry and fluorescence in situ hybridization. Thirty specimens were
      diploid and 33 were aneuploid. In aneuploid samples, the DNA index value ranged
      from 1.3 to 3.1, with a main peak near tetraploid values. Diploid clones were
      present in 21 of 33 aneuploid specimens. Fluorescence in situ hybridization
      analysis showed a heterogeneous degree of alterations in diploid specimens: one
      sample was normal, 16 samples had one to three chromosome alterations involving
      mostly chromosomes 1, 16, and 17, and 13 samples an even higher degree of
      alterations. The 33 aneuploid specimens showed a very high number of signals
      (four, five, or more). All the investigated chromosomes were affected in 23 of 33
      specimens. Alterations in chromosomes 1 and 17 were detected to a similar
      percentage in diploid and aneuploid samples, whereas chromosome 16 monosomy was
      more frequent in diploid samples. Overrepresentation of chromosomes 8, 12, 16,
      and 18 was significantly higher in aneuploid than in diploid samples. Based on
      these results, we suggest that diploid and aneuploid breast carcinomas are
      genetically related. Chromosome 1 and 17 alterations and chromosome 16 monosomy
      are early changes. Allelic and chromosomal accumulations occur during progression
      of breast carcinoma by different mechanisms. The high clone heterogeneity found
      in 17 of 33 aneuploid samples could not be completely explained by
      endoreduplication and led to the suggestion that chromosomal instability concurs
      with aneuploidy development. This different evolutionary pathway might be
      clinically relevant because clone heterogeneity might cause metastasis
      development and resistance to therapy.

PMID- 11241510
TI  - Changes in light scatter properties are a general feature of cell death but are
      not characteristic of apoptotically dying cells.

PMID- 11241513
TI  - Ethical considerations concerning laser medicine.

PMID- 11241515
TI  - Cryogen spray cooling: Effects of droplet size and spray density on heat removal.
AB  - BACKGROUND AND OBJECTIVE: Cryogen spray cooling (CSC) is an effective method to
      reduce or eliminate non-specific injury to the epidermis during laser treatment
      of various dermatological disorders. In previous CSC investigations, fuel
      injectors have been used to deliver the cryogen onto the skin surface. The
      objective of this study was to examine cryogen atomization and heat removal
      characteristics of various cryogen delivery devices. STUDY DESIGN/MATERIALS AND
      METHODS: Various cryogen delivery device types including fuel injectors,
      atomizers, and a device currently used in clinical settings were investigated.
      Cryogen mass was measured at the delivery device output orifice. Cryogen droplet
      size profiling for various cryogen delivery devices was estimated by optically
      imaging the droplets in flight. Heat removal for various cryogen delivery devices
      was estimated over a range of spraying distances by temperature measurements in
      an skin phantom used in conjunction with an inverse heat conduction model.
      RESULTS: A substantial range of mass outputs were measured for the cryogen
      delivery devices while heat removal varied by less than a factor of two. Droplet
      profiling demonstrated differences in droplet size and spray density.
      CONCLUSIONS: Results of this study show that variation in heat removal by
      different cryogen delivery devices is modest despite the relatively large
      difference in cryogen mass output and droplet size. A non-linear relationship
      between heat removal by various devices and droplet size and spray density was
      observed.

PMID- 11241516
TI  - Influence of nozzle-to-skin distance in cryogen spray cooling for dermatologic
      laser surgery.
AB  - BACKGROUND AND OBJECTIVE: Cryogen sprays are used for cooling human skin during
      various laser treatments. Since characteristics of such sprays have not been
      completely understood, the optimal atomizing nozzle design and operating
      conditions for cooling human skin remain to be determined. MATERIALS AND METHODS:
      Two commercial cryogenic spray nozzles are characterized by imaging the sprays
      and the resulting areas on a substrate, as well as by measurements of the average
      spray droplet diameters, velocities, temperatures, and heat transfer coefficients
      at the cryogen-substrate interface; all as a function of distance from the nozzle
      tip. RESULTS: Size of spray cones and sprayed areas vary with distance and
      nozzle. Average droplet diameter and velocity increase with distance in the
      vicinity of the nozzle, slowly decreasing after a certain maximum is reached.
      Spray temperature decreases with distance due to the extraction of latent heat of
      vaporization. At larger distances, temperature increases due to complete
      evaporation of spray droplets. These three variables combined determine the heat
      transfer coefficient, which may also initially increase with distance, but
      eventually decreases as nozzles are moved far from the target. CONCLUSIONS:
      Sprayed areas and heat extraction efficiencies produced by current commercial
      nozzles may be significantly modified by varying the distance between the nozzle
      and the sprayed surface.

PMID- 11241517
TI  - Er:YAG laser skin resurfacing using repetitive long-pulse exposure and cryogen
      spray cooling: I. Histological study.
AB  - BACKGROUND AND OBJECTIVE: To evaluate histologically the characteristics of
      repetitive Er:YAG laser exposure of skin in combination with cryogen spray
      cooling (CSC), and its potential as a method of laser skin resurfacing. STUDY
      DESIGN/MATERIALS AND METHODS: Rat skin was irradiated in vivo with sequences of
      10 Er:YAG laser pulses (repetition rate 20 Hz, pulse duration 150 or 550 micros,
      single-pulse fluence 1.3-5.2 J/cm(2)). In some examples, CSC was applied to
      reduce epidermal injury. Histologic evaluation was performed 1 hour, 1 day, 5
      days, and 4 weeks post-irradiation. RESULTS: A sequence of ten 550-micros pulses
      with fluences around 2 J/cm(2) resulted in acute dermal collagen coagulation to a
      depth of approximately 250 microm, without complete epidermal ablation. CSC
      improved epidermal preservation, but also diminished the coagulation depth. Four
      weeks after irradiation, neo-collagen formation was observed to depths in excess
      of 100 microm. CONCLUSIONS: Dermal collagen coagulation and neo-collagen
      formation to depths similar to those observed after CO(2) laser resurfacing can
      be achieved without complete ablation of the epidermis by rapidly stacking long
      Er:YAG laser pulses. Application of CSC does not offer significant epidermal
      protection for a given dermal coagulation depth.

PMID- 11241518
TI  - Er:YAG laser skin resurfacing using repetitive long-pulse exposure and cryogen
      spray cooling: II. Theoretical analysis.
AB  - BACKGROUND AND OBJECTIVE: To analyze the effects of laser pulse duration and
      cryogen spray cooling (CSC) on epidermal damage and depth of collagen coagulation
      in skin resurfacing with repetitive Er:YAG laser irradiation. STUDY
      DESIGN/MATERIALS AND METHODS: Evolution of temperature field in skin is
      calculated using a simple one-dimensional model of sub-ablative pulsed laser
      exposure and CSC. The model is solved numerically for laser pulse durations of
      150 and 600 microsec, and 6 msec cryogen spurts delivered just prior to ("pre
      cooling"), or during and after ("post-cooling") the 600 microsec laser pulse.
      RESULTS: The model indicates a minimal influence of pulse duration on the extent
      of thermal effect in dermis, but less epidermal damage with 600 microsec pulses
      as compared to 150 microsec at the same pulse fluence. Application of pre- or
      post-cooling reduces the peak surface temperature after laser exposure and
      accelerates its relaxation toward the base temperature to a different degree.
      However, the temperature profile in skin after 50 msec is in either example very
      similar to that after a lower-energy laser pulse without CSC. CONCLUSIONS: When
      applied in combination with repetitive Er:YAG laser exposure, CSC strongly
      affects the amount of heat available for dermal coagulation. As a result, CSC may
      not provide spatially selective epidermal protection in Er:YAG laser skin
      resurfacing.

PMID- 11241519
TI  - Experimental model for the long-term effects of laser resurfacing.
AB  - BACKGROUND AND OBJECTIVE: [corrected] Evaluation of the long-term effects of the
      laser resurfacing on development of the skin cancer after chronic ultraviolet B
      light exposure calls for the development of the appropriate animal model. STUDY
      DESIGN/MATERIALS AND METHODS: The 27 C3H nu/nu nude mice were used in the
      experiment. Five experimental groups were designed to evaluate the effects of
      laser energy delivered. RESULTS: Tru-Pulse(trade mark) Laser System produced char
      free crust immediately after application. There was no histologic difference in
      laser effects on the skin between groups. Complete re-epithelialization occurred
      within 7 days. CONCLUSIONS: An entire lifetime in this mammal model can be
      studied in under 2.5 years. The back skin of the mice can be resurfaced by using
      one pass 500 mJ/cm(2) and complete healing will occur within a 7-day period. We
      believe that establishment of this experimental model has set the stage for the
      further study of the effect of laser energy on sun-damaged skin. Carbon dioxide
      laser resurfacing has become an increasingly popular method of facial
      rejuvenation, allowing the plastic surgeon to repair sun-damaged skin and
      wrinkles. Results obtained by laser resurfacing seem to be long lasting. Carbon
      dioxide laser resurfacing brings about histologic changes in the skin. This
      finding raises a new question: Does carbon dioxide laser skin resurfacing
      modulate the effects of ultraviolet (UV) light exposure on the skin? The purpose
      of this study was to establish a new experimental model for studying the long
      term effects of laser skin resurfacing.

PMID- 11241520
TI  - Intense pulsed light and Nd:YAG laser non-ablative treatment of facial rhytids.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the efficacy and
      safety of the intense pulsed light source (IPL) and the Nd:YAG laser in the
      treatment of facial rhytids. Both systems can be used in a non-ablative manner
      and cause a dermal wound. This is thought to stimulate the production of new
      collagen without epidermal disruption. Non-ablative techniques eliminate the
      downtime that must be endured by patients treated with ablative methods such as
      the carbon dioxide and erbium lasers. STUDY DESIGN/MATERIALS AND METHODS: Fifteen
      subjects with perioral rhytids and Fitzpatrick skin types II and III received
      three-to-five treatments with the IPL using 590 and 755 nm cut-off filters, and
      the 1,064-nm Nd:YAG laser. The subjects were evaluated at 2, 4, 8, 12, and 24
      weeks after the final treatment for improvement in rhytids and presence of any
      side effects. RESULTS: At 6 months, the patient satisfaction score (1-10) was
      comparable in all three groups. Evaluator assessment of improved skin quality was
      also similar in all three treatment groups. Side effects such as blistering and
      erythema were most commonly seen in the subjects treated with the IPL. The least
      discomfort was seen with the Nd:YAG laser. CONCLUSIONS: Although both non
      ablative treatment systems improved facial rhytids presumably by causing a non
      specific dermal wound, the Nd:YAG laser was better tolerated and produced fewer
      side effects.

PMID- 11241521
TI  - Resurfacing of photodamaged skin on the neck with an UltraPulse((R)) carbon
      dioxide laser.
AB  - BACKGROUND AND OBJECTIVE: Successful treatment of facial wrinkles with carbon
      dioxide or erbium laser resurfacing brings about a more youthful appearance of
      the skin on the face. A variable degree of contrast with the untreated skin on
      the neck prompts many patients to request treatment for photodamaged skin on the
      neck. The objective is to investigate the feasibility of resurfacing photodamaged
      skin on the neck with the UltraPulse((R)) carbon dioxide laser. SUDY
      DESIGN/MATERIALS AND METHODS: The study was carried out in two phases. During the
      first phase, a small area on the upper neck was tested with three different
      parameters. The best parameter was then used to treat the neck area in a single
      pass in 10 cases in the second phase. Patients were then evaluated at 3-6 months.
      RESULTS: The three parameters tested were 200 mJ at CPG settings of pattern 3,
      size 9, density 6, 300 mJ at CPG 3-9-5, and 300 mJ at CPG 3-9-6. The latter
      seemed to achieve the best results, and there were no complications at any test
      sites. This setting was used to treat the whole anterior and anterolateral part
      of the neck with a single pass, wiping away the resultant epidermal debris.
      Moderate improvement in color and texture, but no improvement in wrinkling, were
      observed at 3-6 months. However, a mild degree of patchy hypopigmented scarring
      in the lower neck was encountered in three cases, as well as one other case of
      patchy hypopigmentation without textural changes. CONCLUSIONS: Despite some
      obvious improvements, the risk of scarring and hypopigmentation with the tested
      parameters out-weighs the potential benefits. The lower part of the neck
      responded very differently from the upper part. Alternative strategies to achieve
      better results are discussed.

PMID- 11241523
TI  - Terminal hair growth after full thickness skin graft: Treatment with normal mode
      ruby laser.
AB  - BACKGROUND AND OBJECTIVE: Treatment of hirsutism is often unsatisfactory with
      many of the currently used methods providing only temporary improvement. The use
      of lasers for hair removal has shown promising results and treatment by using the
      normal mode ruby laser has provided reduction in hair numbers sustained on follow
      up. We report a woman who developed terminal hair growth at the site of a full
      thickness skin graft and describe her successful treatment with the normal mode
      ruby laser.

PMID- 11241522
TI  - Diode laser hair removal of the black patient.
AB  - BACKGROUND AND OBJECTIVE: The 810-nm wavelength diode laser can safely and
      successfully treat all skin types, including dark pigmented skin. STUDY
      DESIGN/METHODS: Eight Fitzpatrick level V-VI skin type patients, four of which
      presented with the diagnosis of pseudofolliculitis barbae, were treated with the
      diode laser for hair removal using low-energy settings and long pulse duration.
      RESULTS: All eight patients had excellent results with unwanted hair greatly
      reduced, and pseudofolliculitis barbae resolved. CONCLUSIONS: Diode lasers can be
      used on dark pigmented skin with positive outcomes. Complications such as
      hypopigmentation, or hyperpigmentation occurred, but all were transient and
      resolved within a few months.

PMID- 11241524
TI  - Histologic evaluation of a millisecond Nd:YAG laser for hair removal.
AB  - BACKGROUND: Hirsutism and hypertrichosis are common problems. Laser-assisted hair
      removal has recently become a popular method to remove unwanted hair. However,
      histologic changes of the hair follicle after exposure to laser continue to
      require further investigation. OBJECTIVE: To determine the thermal effect of a
      millisecond Nd:YAG hair removal laser. METHODS: Six patients with black hair were
      treated with 50 msec pulsed Nd:YAG laser at fluences 30, 50 or 100 J/cm(2).
      Histologic examinations were performed on each laser-treated site at 24-72 hours
      after laser exposure. RESULTS: Fluence-dependent selective thermal injury to
      follicles was seen. The average depth of acute laser injury at fluences 30, 50
      and 100 J/cm(2) were 1.06, 0.85 and 1.11 millimeters, respectively. CONCLUSIONS:
      Long-pulsed millisecond Nd:YAG lasers produce selective thermal damage of hair
      follicles. Varied laser fluences used in this study did not statistically alter
      the degree of thermal injury.

PMID- 11241525
TI  - Optimizing free electron laser incisions at 6.45 microm with computer-assisted
      surgical techniques and the utilization of a heat-conducting template.
AB  - BACKGROUND AND OBJECTIVE: We sought to optimize laser incisions by evaluating the
      effects of varying the slit width of a heat-conducting template and the step size
      with the Computer-Assisted Surgical Techniques (CAST) system on free electron
      laser (FEL) incisions at 6.45 microm. STUDY DESIGN/MATERIALS AND METHODS:
      Stainless steel calipers were used as a heat-conducting template on human skin in
      vitro. The CAST system made the incisions as a series of spot ablations with set
      step sizes of 50 microm or 1,250 microm. At each step size, incisions were made
      with or without the calipers, by using varying slit widths. Histologic specimens
      were analyzed for lateral thermal damage over the entire depth of the incision
      and over the superficial 150 microm of dermis. RESULTS: Lateral thermal damage
      over the superficial 150 microm of dermis was most significantly reduced with the
      calipers at a slit width approximating the FEL's beam diameter (636 microm +/-
      100 microm). Also, incisions made with the larger step size (1,250 microm) had
      significantly less lateral thermal damage over the entire depth of the incision.
      CONCLUSIONS: The use of a heat-conducting template with an aperture approximating
      the FEL's beam diameter and larger step size improved FEL incisions at 6.45
      microm.

PMID- 11241526
TI  - Laser assisted skin closure (LASC) by using a 815-nm diode-laser system
      accelerates and improves wound healing.
AB  - BACKGROUND AND OBJECTIVE: This study aimed to evaluate a 815-nm diode-laser
      system to assist wound closure to accelerate and improve healing process. STUDY
      DESIGN/MATERIALS AND METHODS: A total of 25 male hairless rats (mutant OFA
      Sprague-Dawley rats, IFFA-CREDO, L'Arbresle, France) with four dorsal skin
      incisions were used for the study. For each wound, the good apposition of the
      edges was obtained with buried absorbable suture. In the laser group, the laser
      beam was applied spot by spot through a transparent adhesive dressing along two
      incisions with the following parameters: 1.5 W; 3 seconds; spot diameter, 2 mm;
      fluence, 145 J/cm(2). Both control wounds were closed with conventional suture
      techniques. The duration of the closure procedure was noted for each group.
      Clinical examination, histologic study, and measurement of tensile strength were
      performed at 3, 7, 15, and 21 days after surgery. Determination of activation of
      heat shock protein 70 (Hsp70) through immunocytochemistry was performed at days 1
      and 7. RESULTS: LASC was 4 times faster to process than conventional suture: 1
      minute 49 +/- 20.6 seconds vs. 7 minutes 26 +/- 62.2 seconds. In the laser group,
      healing was accelerated resulting in a more indiscernible scar than in the
      control groups. Histologic aspect was better with earlier continuous epidermis
      and dermis and a thinner resulting scar. Tensile strength was 30 to 58% greater
      than in control groups at 7 and 15 days (P < 0.001). Expression of Hsp70 was
      markedly induced in skin structures examined after laser exposure. CONCLUSIONS:
      This study shows the ability of the 815-nm diode-laser system to assist wound
      closure leading to an acceleration and an improvement of wound healing with
      indiscernible resulting scar. The mechanisms of this phenomenon are still unclear
      but further investigations are in progress to attempt to explain them.

PMID- 11241527
TI  - Histologic evaluation of skin damage after overlapping and nonoverlapping
      flashlamp pumped pulsed dye laser pulses: A study on normal human skin as a model
      for port wine stains.
AB  - BACKGROUND AND OBJECTIVE: In the treatment of port wine stains (PWS) with the
      flashlamp pumped pulsed dye laser (FPPDL), no consensus exists about overlapping
      of pulses. The advantage of overlapping pulses is homogeneous lightening of the
      PWS; the risk is redundant tissue damage. The aim of this study was to determine
      the histopathologic effect on human skin of pulsed dye laser pulses with various
      degrees of overlap, with normal human skin as a model for PWS. STUDY
      DESIGN/MATERIALS AND METHODS: Eighteen healthy white volunteers were irradiated
      with pulsed dye laser pulses with increasing radiant exposure and with different
      degrees of overlap. Biopsy samples were taken and histologically analysed.
      RESULTS: Overlapping of pulses on normal human skin enhances depth of vascular
      damage with approximately 30%. Adjacent pulses also show this effect. We found no
      histologic signs of serious damage to epidermis or dermal connective tissue by
      using radiant exposure levels of 6-8 J/cm(2), regardless of pulse application.
      CONCLUSIONS: Reasoning that the mechanism of tissue injury is comparable for
      normal and PWS skin, we conclude that it is safe to treat PWS with overlapping
      FPPDL pulses to achieve homogeneous lightening.

PMID- 11241528
TI  - Introduction of the flash-lamp pulsed-dye laser treatment of facial port-wine
      stains in childhood: A case of health care technology assessment.
AB  - BACKGROUND AND OBJECTIVE: Lasers have been used in the treatment of port-wine
      stains (PWS) for more than 30 years. With the introduction of the flash-lamp
      pulsed-dye laser (FPDL) it was assumed that infants could be treated safely,
      effectively, and probably more efficiently. Nowadays, FPDL treatment is an
      established form of treatment of PWS in childhood. STUDY DESIGN/MATERIALS AND
      METHODS: On the basis of the iterative Health Care Technology Assessment (HCTA)
      loop, we examined whether sufficient evidence from evaluations has been present
      to support the introduction of FPDL treatment for facial PWS at an early age.
      Such an assessment requires an interdisciplinary approach focusing on aspects of
      safety, efficacy, effectiveness, quality of life, costs, and the ethical issues
      of treatment. RESULTS: Assessment of the FPDL in PWS treatment of children did
      not follow the model of medical innovation and evaluation. Most assessments have
      been focused on laser applications that were already in clinical use. Efficacy
      and effectiveness of laser treatment have been the major concern in most
      assessments. Only a few studies have looked at costs and ethical aspects of
      treating children. CONCLUSIONS: The introduction and diffusion of the use of the
      FPDL in the treatment of PWS in childhood were uncontrolled, and the field was
      not prepared to use this technique properly. We believe that this nonadherence to
      the iterative HCTA model reflects the gradual way by which innovations find their
      way into clinical practice.

PMID- 11241529
TI  - Follow-up investigations in uncultured amniotic fluid cells after uncertain
      cytogenetic results.
AB  - Fluorescence in situ hybridization (FISH) on uncultured amniotic fluid (AF) cells
      is a widespread technique for the rapid prenatal detection of specific chromosome
      aberrations. During a 6-year period (1993-1998) we used FISH for quick follow-up
      investigations in uncultured AF cells after finding an uncertain chromosome
      aberration in a first chorionic villus (CV) or AF sample in 79 cases. These FISH
      results were compared with conventional cytogenetic results of the AF cell
      cultures in all cases. We found discrepant FISH and cytogenetic results in four
      instances. In general, FISH on uncultured AF cells proved to be a reliable
      technique for the rapid differentiation between confined placental mosaicism and
      true fetal mosaicism, and between pseudomosaicism and true mosaicism,
      respectively. Uncultured cells may sometimes even better reflect chromosomal
      mosaicism than cultured cells, since they are not subject to culture induced
      selection mechanisms. However, we found evidence that exceptional cases of tissue
      confined mosaicism may go undetected in uncultured cells.

PMID- 11241530
TI  - Antenatal genetic screening for congenital nephrosis.
AB  - This study was undertaken to study the applicability of genetic antenatal
      screening for the Finnish type of congenital nephrosis (CNF), which is a
      recessive disorder leading to nephrotic syndrome from birth. At Kuopio University
      Hospital, a total of 1303 pregnant women were offered carrier screening for CNF
      at the time of first trimester nuchal fold translucency measurement when fetally
      derived alpha-fetoprotein is still produced by the yolk sac. Two mutations of the
      nephrin (NPHS 1) gene, accounting for approximately 95% of affected alleles, were
      tested by two PCR tests. Uptake of the gene test was 91.0% (n=1183). Altogether
      38 female carriers were found; a population carrier frequency of 1 in 31. Their
      partners were tested and two of them were also found to be carriers. In these two
      pregnancies invasive prenatal diagnosis was offered and accepted, and the results
      indicated one carrier and one affected fetus. Carrier screening is an effective
      and well-accepted method for antenatal screening for fetal CNF. Direct mutation
      analysis involves markedly less invasive procedures compared with serum alpha
      fetoprotein (AFP) screening, and the diagnosis was clear-cut. The results
      indicate that in single-gene disorders genetic testing is suitable for antenatal
      screening.

PMID- 11241531
TI  - Prenatal diagnosis of congenital toxoplasmosis by duplex real-time PCR using
      fluorescence resonance energy transfer hybridization probes.
AB  - The diagnosis of congenital toxoplasmosis frequently relies on PCR tests of
      amniotic fluid (AF). A duplex real-time quantitative PCR test based on
      fluorescence resonance energy transfer was developed to quantify the parasite
      load and to decrease the risk of contamination. An internal control based on the
      detection of 10 pg mouse DNA added to the AF was included to check for PCR
      efficiency. The relationship between the parasite load and the occurrence of
      ultrasonographic abnormalities in 87 samples of AF was analyzed. Seven AF (8%)
      had a parasitic load > 10(3); 14 (16%) had > 10(2)-< or =10(3); 26 (30%) had > 10
      < or = 10(2); and 40 (46%) had < or = 10 parasites/ml. Four of the six AF with
      cerebral ventriculomegaly had >10(3) parasites/ml. The other two had 130 and 24
      parasites/ml, respectively. No parasitic loads of > 10(3) parasites/ml and no
      ultrasonographic abnormalities were observed in the 11 AF with maternal
      toxoplasmosis in the third trimester. Therefore, there is a trend to associate
      high parasite count with ultrasonographic abnormality, but the main concern
      remains early maternal infection. The importance of quantification should be
      better evaluated with postnatal studies. The duplex LightCycler PCR test
      currently provides rapid and safe results.

PMID- 11241532
TI  - Prenatal diagnosis and genetic analysis of type I and type II thanatophoric
      dysplasia.
AB  - Thanatophoric dysplasia (TD) is one of the most common neonatal lethal skeletal
      dysplasias. Prenatal sonographic and molecular genetic diagnoses of three cases
      of TD type I (TD1) and one case of TD type II (TD2) are presented here. Two
      fetuses of TD1 were characterized by polyhydramnios, macrocephaly, short limbs, a
      narrow thoracic cage and curved short femora, but without a cloverleaf skull at
      27 and 31 weeks' gestation, respectively. The third fetus with TD1 was, however,
      not associated with macrocephaly, polyhydramnios, chest narrowing and severe
      femoral bowing on prenatal ultrasound at 18 weeks' gestation. The TD2 fetus was
      characterized by polyhydramnios, short limbs, a narrow thoracic cage, straight
      short femora, hydrocephalus and a cloverleaf skull at 24 weeks' gestation. Three
      dimensional ultrasound was able to enhance the visualization of thickened,
      redundant skin folds and craniofacial and limb deformities associated with TD.
      Molecular analysis of the fibroblast growth factor receptor 3 (FGFR3) gene by
      restriction enzyme digestion analysis and direct sequencing using cultured
      amniotic fluid cells or cord blood cells revealed a missense mutation of 742C-->T
      (Arg248Cys) in all cases with TD1 and a missense mutation of 1948A-->G
      (Lys650Glu) in the case with TD2. The present report shows that adjunctive
      applications of molecular genetic analysis of the FGFR3 gene and three
      dimensional ultrasound are useful for prenatal diagnosis of TD.

PMID- 11241533
TI  - Acrocentric chromosome polymorphisms: beware of cryptic translocations.
AB  - Cryptic translocations may escape diagnosis, especially when they implicate
      chromosomal regions that are known to be polymorphic in the human karyotype. We
      describe a case of postnatal diagnosis of Beckwith-Wiedemann syndrome (BWS) due
      to an unbalanced translocation that had not been diagnosed in the fetal
      karyotype. This first cytogenetic analysis revealed that one chromosome 14
      presented as a common acrocentric short arm polymorphism. Further analyses after
      birth, using C-banding, NOR staining and fluorescence in situ hybridization
      (FISH) with telomeric probes, revealed that it was the result of an unbalanced de
      novo t(11;14)(p15;p13) translocation leading to partial 11p trisomy and to BWS.
      Prenatal cytogenetic management of such apparently inoffensive chromosome markers
      is discussed.

PMID- 11241534
TI  - First-trimester diagnosis of late-infantile neuronal ceroid lipofuscinosis
      (LINCL) by tripeptidyl peptidase I assay and CLN2 mutation analysis.
AB  - Late-infantile neuronal ceroid lipofuscinosis (LINCL) is a progressive
      neurodegenerative disorder caused by the deficiency of lysosomal tripeptidyl
      peptidase I (TPP-I) encoded by the CLN2 gene. We report the first case of early
      prenatal diagnosis of LINCL by combined enzyme and mutation analysis. TPP-I
      activity in chorionic villi (CV) was less than 2% of the mean normal control
      level and g.1946A > G and g.3670C > T mutations were demonstrated, as in the two
      previously affected children. After termination of pregnancy, TPP-I deficiency
      was confirmed in cultured CV cells and in the fetal skin fibroblasts. The
      expression of unequivocal TPP-I deficiency in CV demonstrates that enzyme assay
      is a reliable option for prenatal diagnosis of LINCL.

PMID- 11241535
TI  - Prenatal diagnosis of mosaic ring chromosome 13 with anencephaly.
AB  - We report on the prenatal diagnosis, genetic analysis and clinical manifestations
      of a second-trimester fetus with mosaic ring chromosome 13 and anencephaly. A 35
      year-old, gravida 3, para 2 woman was referred for genetic counselling at 23
      weeks' gestation because of an elevated maternal serum alpha-fetoprotein level of
      2.386 multiples of the median. Prenatal ultrasonography showed intrauterine
      growth retardation and anencephaly. Amniocentesis revealed a karyotype of de novo
      mos 46,xx,r(13)(p11q32)/45,xx,-r(13) [corrected] (77%/23%). Molecular genetic
      analysis by quantitative fluorescent polymerase chain reaction (PCR) with small
      tandem repeat markers specific for chromosome 13 rapidly confirmed the maternal
      origin of the aberrant chromosome and determined the breakpoint at 13q32 between
      D13S225 (present) and D13S147 (absent). Our present finding indicates that
      anencephaly can be due to mosaic r(13) with a terminal deletion of 13q32-13q34
      and an additional secondary rearrangement of loss of r(13). We propose that
      cytogenetic analysis is beneficial and warranted in pregnancies with fetal neural
      tube defects.

PMID- 11241536
TI  - Use of the Kleihauer test to detect fetal erythroblasts in the maternal
      circulation.
AB  - Non-invasive prenatal diagnosis of aneuploidies on fetal nucleated erythrocytes
      present in the maternal circulation is hampered by the extremely small cell
      number of uncertain origin (70% of erythroblasts circulating during pregnancy
      have a maternal origin). Therefore, a method allowing selection of the fetal
      cells among the maternal cells is indispensable after the erythroblast enrichment
      step. In the present study, after an erythroblast enrichment step on a ficoll
      gradient followed by a positive immuno-magnetic selection with anti-CD71 or anti
      GPA antibodies, a rapid, simple and direct chemical staining method adapted from
      the classical Kleihauer test was developed to select fetal cells. Precise
      differentiation between fetal and maternal erythroblasts is based on the
      constitutional difference between fetal and adult haemoglobin (Hb). The fetal
      cells appear with an intense pink cytoplasmic staining while maternal cells with
      adult haemoglobin are colourless. Preservation of the cytoplasmic integrity
      allows one to distinguish morphological characteristics and to visualize
      simultaneously nuclear hybridization signal by FISH (fluorescent in situ
      hybridization). This approach was tested by FISH analysis using dual-colour X-
      and Y-specific DNA probes on blood samples from 15 pregnant women, with the
      results being compared to cytogenetic or sonographic sex determination. For 12
      pregnancies fetal sex was determined successfully (5 XY/7 XX), in two cases in
      situ hybridization failed, and in one case no fetal erythroblast was observed
      after the Kleihauer test. The selection method was applied to a pregnancy at risk
      for cystic fibrosis (CF). After a Kleihauer test, fetal erythroblasts were
      collected by microdissection, whole genomic DNA was amplified by primer extension
      pre-amplification (PEP) followed by a nested CF PCR. The fetal genotype was
      successfully characterized and confirmed by conventional prenatal diagnosis.

PMID- 11241537
TI  - Prenatal measurement of testicular diameter by ultrasonography: development of
      fetal male gender and evaluation of testicular descent.
AB  - Prenatal ultrasonography has evolved through advancements in imaging technology
      and observer experience. The purpose of the present study was to evaluate fetal
      testicular descent and diameter in relation to gestational age. A prospective
      cross-sectional study on 331 fetuses from an unselected population underwent a
      detailed assessment of testicular descent and diameter at 20-40 weeks' gestation
      by means of transabdominal sonography (91.2%) and transvaginal sonography (8.8%)
      when necessary. Fetal gender was identified in the transverse and sagittal planes
      and maximum testicular diameter was measured. The mean testicular diameter (in
      millimeters) per week and the 95% confidence interval (CI) were defined.
      Testicular descent was not observed prior to 23 weeks' gestation, with 6.6% of
      the fetuses having one testis descended at 23 weeks and 98.2% after 32 weeks. A
      linear relationship between testicular diameter and gestational age was observed.
      The present results chart the time course for testicular descent and provide a
      centile chart for fetal testicular diameter from 25 to 40 weeks' gestation. These
      findings may aid prenatal diagnosis of associated abnormal conditions as well as
      investigations into the clinical finding of abnormal testicular size.

PMID- 11241538
TI  - Sex-related differences in the development of the human fetal corpus callosum: in
      utero ultrasonographic study.
AB  - A cross-sectional study of pregnant women presenting for routine fetal
      ultrasonographic examination was conducted at the Obstetric Ultrasonographic Unit
      of the Chaim Sheba Medical Center to investigate in utero development of the
      fetal corpus callosum (CC) in relation to fetal gender. A total of 255
      consecutive healthy fetuses of low-risk pregnancies between 16 and 36 weeks'
      gestation were examined. Thickness and width of the anterior mid-body of the CC
      were measured in the mid-coronal plane, and length was measured in the mid
      sagittal plane. Fetal gender was determined by an independent observer. Female
      fetuses had statistically significantly thicker CC than males for each
      gestational age. The mean +/- standard deviation (SD) CC thickness in females was
      2.13 +/- 0.8 mm [95% confidence interval (CI) 1.98-2.28] while the mean +/- SD CC
      thickness in males was 1.8 +/- 0.5 mm (95% CI 1.70-1.89; p < 0.01). The length
      and width of the CC during gestation did not differ significantly between the
      sexes. Corpus callosum size as a function of gestational age (GA) in both sexes
      was expressed by linear regression equations. The correlation coefficients r =
      0.93, r = 0.61 and r = 0.62 for length, width and thickness, respectively, in
      males and r = 0.92, r = 0.71 and r = 0.72 in females were found to be
      statistically significant (p < 0.01). The present data suggest that female
      fetuses have a thicker CC than males. These findings support previous studies
      suggesting sex dimorphism of human CC and raise the possibility that prenatal sex
      hormones may play a role in determining callosal development.

PMID- 11241539
TI  - Fetal varicella-herpes zoster syndrome in early pregnancy: ultrasonographic and
      morphological correlation.
AB  - We report a case of an intrauterine fetal infection by the varicella-herpes
      zoster virus following maternal varicella at 17 weeks' amenorrhea. Prenatal
      diagnosis of fetal infection was confirmed by serology and fetal damage by
      ultrasonography. Autopsy of the fetus showed multiorgan manifestation with
      disseminated foci of necrosis and microcalcifications, encephalitis and
      unilateral segmental skin scarring with an underlying hypoplastic fixed lower
      limb. The placenta showed a multifocal chronic villitis with multinucleated giant
      cells. The lesions included segmental anomalies and multiorgan damage.

PMID- 11241540
TI  - Antenatal sonographic findings of right pulmonary agenesis with ipsilateral
      microtia: a possible new laterality association.
AB  - Right pulmonary agenesis is a rare congenital malformation which results in
      secondary dextrocardia in situs solitus. Ipsilateral microtia in this context
      composes a laterality syndrome. The prenatal sonographic findings of this
      abnormality have not been previously reported. We describe the association of
      dextrocardia in situs solitus, intact diaphragm and right microtia. This was
      sonographically diagnosed at mid-gestation in an euploid fetus. Surgical
      evacuation of the pregnancy confirmed the external malformation. Laterality
      association should be assessed in a fetus with sonographic findings of pulmonary
      agenesis. The differential diagnosis and updated literature review is presented.

PMID- 11241541
TI  - Outcome of fetal urinary tract anomalies associated with multiple malformations
      and chromosomal abnormalities.
AB  - The purpose of this study was to identify prognostic factors and describe the
      outcome of prenatally detected renal anomalies associated with multiple
      malformations and chromosomal defects. Forty-one fetuses were included in the
      analysis. Prenatal ultrasound reports, neonatal records and autopsy information
      were retrospectively reviewed. Prognostic factors associated with fetal
      echography and clinical and laboratory findings on admission were studied. Data
      were analyzed by univariate analysis in which variables associated with adverse
      outcome were identified by the Chi-square test or Fisher exact test. The
      abnormalities associated with renal anomalies were divided into three groups:
      chromosomal defects (21%), previously described syndromes and conditions (24%),
      and new sporadic conditions (55%). Of 41 children admitted, 30 (76%) died during
      the perinatal period. The presence of oligohydramnios was significantly
      associated with an adverse outcome (OR=11, p=0.05). Male gender was a protective
      factor against death during the perinatal period (OR=0.11, p=0.01). In
      conclusion, prenatally detected renal anomalies associated with multiple
      malformations and chromosomal defects had a poor prognosis. The presence of
      oligohydramnios increased the risk of death, and male gender had a protective
      role against poor outcome.

PMID- 11241542
TI  - Selective feticide of an affected fetus in the second trimester has comparable
      risks to those in the first trimester.
AB  - The broad acceptance of prenatal diagnosis of various genetic diseases leads to
      an ever-increasing number of parturients with twin gestations undergoing
      selective feticide of an affected fetus. In most of the cases, delayed diagnosis
      leads to second trimester reduction. The aim of the present study was to
      investigate whether this procedure can be performed in the second trimester with
      results comparable to those obtained when it is performed in the first trimester.
      There was a 5.6% miscarriage rate in the group reduced in the first trimester
      (n=18, Group A) and an 8.3% miscarriage rate in the group reduced in the second
      trimester (n=48, Group B). The mean weight of neonates in the first group was
      2780 g, and in the second group 2620 g. The mean gestational age at delivery was
      36.7 weeks for Group A and 35.1 weeks for Group B. No significant differences
      were observed for any two-paired values considered. There was no perinatal
      mortality in either group. We therefore conclude that selective feticide of an
      affected fetus is as safe in the second trimester as it is in the first.

PMID- 11241543
TI  - Quality of written information used in Down syndrome screening.
AB  - A qualitative assessment was performed on 81 leaflets used in maternal serum Down
      syndrome screening from National Health Service (NHS) obstetric units and private
      screening services. Quality was assessed by factual content, presentation and
      reading ease and this was amalgamated into a single overall score expressed as a
      percentage of the maximum possible score. Eleven (14%) leaflets included all
      eight factual items recommended by the Royal College of Obstetricians and
      Gynaecologists (RCOG); only one included these and a further nine items
      recognised as important to the consumer. Three (4%) leaflets contained
      information that was incorrect and 17 (21%) that was misleading or inconsistent.
      Using published criteria six (7%) leaflets were well presented and ten (12%) were
      fairly easy to read. The average reading age was 13-14 years. The overall quality
      score showed that five leaflets had 80% or more of the total possible score.
      However a substantial number, 15 (19%), were totally unacceptable having scores
      of 40% or less. In general the quality of leaflets used in the UK is considered
      poor. A national peer-reviewed leaflet should be prepared which can be modified
      to suit local policy.

PMID- 11241544
TI  - Maternal serum human chorionic gonadotrophin levels in systemic lupus
      erythematosus and antiphospholipid syndrome.
AB  - Maternal serum human chorionic gonadotrophin (hCG) levels were measured during
      the second and the third trimesters of pregnancy in patients with either systemic
      lupus erythematosus (SLE) or primary antiphospholipid syndrome (APS). All results
      were expressed in multiples of the gestation-specific normal medians (MoM). The
      median MoM level in 17 samples from SLE patients was 1.48 compared with 0.79 MoM
      in 99 controls of similar gestation (p < 0.002, Wilcoxon Rank sum test). In
      contrast the median MoM level in 19 samples from primary APS patients was only
      1.14. These preliminary findings should be further studied to evaluate the
      implications for Down syndrome screening, detection of SLE cases during pregnancy
      and the prediction of adverse outcome in SLE gestations.

PMID- 11241545
TI  - Use of videotapes for viewing at home to inform choice in Down syndrome
      screening: a randomised controlled trial.
AB  - A randomised trial was carried out to assess the effect of a Down syndrome
      screening video on test uptake, knowledge and psychological stress. A total of
      2000 women referred for antenatal care were allocated to two equal groups: one to
      be sent a video to their home, before their hospital booking visit, and a control
      group. All women also received screening information in the form of a leaflet
      before booking and from a midwife at booking. The video had no effect on the
      screening uptake rate: 638/993 (64.2%) and 652/1007 (64.7%) in the video and
      control groups, respectively. Women were requested to return the video for reuse
      in other pregnancies and 612 (62%) did so. A subset of 1200 women were selected
      to be posted at 17-19 weeks' gestation a self-completed questionnaire to assess
      the psychological endpoints. Knowledge of screening was increased in the video
      group with a mean score of 7.3 compared with 6.7 in the controls, a statistically
      significant difference (t=3.24, p=0.0005). There were no significant differences
      between the groups in specific worries about abnormalities in the baby, and
      general anxiety. We conclude that a video can increase knowledge without
      affecting the uptake of the test, or psychological stress.

PMID- 11241546
TI  - Current awareness in prenatal diagnosis.
AB  - In order to keep subscribers up-to-date with the latest developments in their
      field, John Wiley & Sons are providing a current awareness service in each issue
      of the journal. The bibliography contains newly published material in the field
      of prenatal diagnosis. Each bibliography is divided into 17 sections: 1 Books,
      Reviews & Symposia; 2 General Interest; 3 Normal Fetal Development; 4
      Gametogenesis and Pre-implantation Diagnosis; 5 First Trimester Diagnosis; 6
      Second Trimester Diagnosis; 7 Fetal Diagnosis by Ultrasound and Other Imaging; 8
      Maternal Screening; 9 Screening for Carriers of Genetic Abnormality; 10
      Technological Developments; 11 Confined Placental Mosaicism and Uniparental
      Disomy; 12 Molecular Cytogenetics; 13 Fetal Cells in Maternal Circulation; 14
      Fetal Therapy; 15 Psychosocial Aspects; 16 Epidemiology and Environmental
      Factors; 17 Developmental Pathology. Within each section, articles are listed in
      alphabetical order with respect to author. If, in the preceding period, no
      publications are located relevant to any one of these headings, that section will
      be omitted

PMID- 11241547
TI  - A phase II trial of estramustine and etoposide in hormone refractory prostate
      cancer: A Southwest Oncology Group trial (SWOG 9407).
AB  - BACKGROUND: The combination of oral estramustine and oral etoposide has generated
      response rates of 40-50% in patients with hormone refractory prostate cancer in
      single institution trials. This study tested this regimen in a multi
      institutional setting. METHODS: Fifty-five patients were accrued over a period of
      4 months between 1 March 1996 and 1 July 1996. Two patients were not analyzable
      and two patients were ineligible. They were given an oral regimen consisting of
      estramustine 15 mg/kg/day (capped at 1120 mg per day) and etoposide 50
      mg/M(2)/day, days 1-21 every 28 days. Patients received a median of two cycles of
      therapy. RESULTS: Toxicities included 11 patients (20%) with grades 3 or 4
      granulocytopenia, 5 patients (10%) with grades 3 or 4 edema, and 3 patients (6%)
      with a thrombotic event. There were two treatment-related deaths, one as a result
      of anemia and the other as a result of a myocardial infarction. Of the 32 men who
      received at least 2 cycles of therapy, 7 men (22%) demonstrated a partial
      response to this regimen as measured by prostate-specific antigen (PSA) criteria
      of a 50% decline from pretreatment values. CONCLUSIONS: This trial demonstrates
      the toxicity of estramustine delivered in high dose. It also illustrates the
      difficulty of conducting phase II trials in prostate cancer in the cooperative
      group setting where the experience and comfort level of oncologists with new
      agents is less than that of the physicians at the institution where the therapy
      was developed. As the activity of this regimen with low-dose estramustine is
      defined, further multi-institutional studies may be warranted.

PMID- 11241548
TI  - Voltage-gated K(+) channel activity in human prostate cancer cell lines of
      markedly different metastatic potential: distinguishing characteristics of PC-3
      and LNCaP cells.
AB  - BACKGROUND: Although ion channels are known to contribute to a variety of basic
      cellular behaviors involved in the metastatic cascade, their role in metastasis
      per se has only recently been questioned. The hypothesis tested was whether K(+)
      channels were different between strongly metastatic PC-3 and weakly metastatic
      LNCaP human prostate cancer cell lines. METHODS: The whole-cell configuration of
      the patch clamp recording technique was used to record voltage-gated currents
      from LNCaP and PC-3 cell lines. The responses to different voltage-clamp
      protocols, sensitivity to external Ca(2+), and addition of drugs and toxins were
      explored. RESULTS: Voltage-gated K(+) current density was significantly larger in
      LNCaP than PC-3 cells. In addition, the K(+) currents in a sub-population of PC-3
      cells were Ca(2+)-sensitive. These properties reflected the differential
      metastatic character of the cells, the PC-3 cells appearing potentially more
      "excitable". CONCLUSIONS: Prostate cancer cells of varying metastatic ability can
      be distinguished by their ion channel characteristics. The possible
      contribution(s) of K(+) channel activity to development of malignancy needs
      exploration.

PMID- 11241549
TI  - The effect of bicalutamide on prostate histology.
AB  - BACKGROUND: Nonsteroidal antiandrogens are commonly used in the treatment of
      prostate cancer, but more clinical and laboratory studies on patients with benign
      as well as malignant prostate diseases are required to define their exact role.
      METHODS: Light microscopic examination of perineal prostate biopsies of 21 men
      with BPH was performed pretreatment, after 24 weeks of therapy with 50 mg
      bicalutamide (Casodex) or placebo and 24 weeks after end of treatment. We
      assessed whether it was possible to distinguish between patients having received
      bicalutamide or placebo based on a general histological examination. In addition,
      the volume fractions of the prostatic epithelial, luminal, and stromal
      compartments were determined by morphometry. RESULTS: Histological changes
      following treatment were uncharacteristic and patients treated with bicalutamide
      were not identified. At morphometry prior to therapy, the prostates of the study
      participants consisted of 91.8% stroma (range 78.9-97.2), 5.5% epithelium (range
      1.4-14.1) and 2.7% glandular lumen (range 0.8-7.5). Changes in the relative
      content of the three tissue components following treatment were not statistically
      significant. CONCLUSIONS: We did not observe consistent morphological changes in
      the prostate following treatment with bicalutamide at a dose of 50 mg daily.
      However, this dose is lower than the 150 mg dose presently recommended for
      bicalutamide monotherapy.

PMID- 11241550
TI  - Characteristics of normal prostate vascular anatomy as displayed by power
      Doppler.
AB  - BACKGROUND: To define the vascular anatomy of the normal prostate as depicted by
      power Doppler and to provide baseline data for evaluation of this modality in the
      diagnosis and management of prostatic disease. METHODS: The vascular anatomy of
      40 subjects was studied. Power Doppler images were correlated with corresponding
      gray-scale images. Doppler spectral waveform measurements were obtained for the
      vessels identified. RESULTS: Separate branches of the capsular vessels were
      visualized clearly, distributed radially in the peripheral and central zones and
      converging toward the center of the gland. Urethral vessels were visualized in
      the transition zone coursing from bladder neck to verumontanum. The neurovascular
      bundles were identified posterolaterally along the length of the gland. No
      significant difference between the resistive indexes of the urethral and capsular
      vessels was identified (P = 0.595), although there was a significant difference
      between the resistive index of the neurovascular bundles and that the prostatic
      vessels (P < 0.001). CONCLUSIONS: The vascular anatomy of the normal prostate as
      displayed by power Doppler demonstrates a reproducible and symmetric flow
      pattern. Power Doppler is highly sensitive in depicting blood flow, the number,
      course, and continuity of vessels more readily than other imaging modalities,
      such as color Doppler. These data should allow comparison of the vascular anatomy
      of the normal prostate with that of the prostate with diseases such as prostate
      cancer and benign prostatic hyperplasia.

PMID- 11241551
TI  - Ceramide-induced cell death in the prostate cancer cell line LNCaP has both
      necrotic and apoptotic features.
AB  - BACKGROUND: Prostate cancer is the second leading cause of cancer death in men.
      The most common treatment of prostate cancer is androgen ablation therapy which
      leads to regression of the tumor due to increased cell death. However, at later
      stages, the tumor becomes resistant to androgen ablation. Ceramide is a lipid
      second messenger that mediates cell death in prostate cancer cells. Previous
      studies suggested that ceramide may cause either apoptosis or growth arrest in
      the androgen-responsive prostate cancer cell line LNCaP. However, the molecular
      details of ceramide-induced cell death in LNCaP cells remain to be elucidated.
      METHODS: To investigate the mechanisms of cell death in LNCaP cells, we used
      various methods, including cell viability assays, fluorescence image analysis,
      internucleosomal DNA fragmentation analysis, Western blotting, and protein kinase
      assays. RESULTS: Ceramide caused LNCaP cell death without exhibiting typical
      signs of apoptosis, such as internucleosomal DNA fragmentation and poly(ADP)
      ribose-polymerase (PARP) proteolysis. In addition, the general caspase inhibitor
      z-VAD-fmk did not alter ceramide-induced cell death in LNCaP cells, whereas it
      efficiently inhibited thapsigargin-induced apoptosis under similar conditions.
      However, ceramide treatment of LNCaP cells resulted in nuclear fragmentation,
      which is characteristic of apoptosis. Ceramide induced a strong and prolonged
      activation of c-Jun N-terminal Kinase (JNK) that correlated very well with the
      time course of cell death. Whereas the PKC inhibitor bisindolylmaleimide
      prevented phorbol ester-induced apoptosis in LNCaP cells, it did not affect
      ceramide-induced cell death. These results suggest that LNCaP cell death induced
      by ceramide progresses through a novel pathway that is more necrotic than
      apoptotic.

PMID- 11241553
TI  - Receiver-operating characteristic as a tool for evaluating the diagnostic
      performance of prostate-specific antigen and its molecular forms--What has to be
      considered?
AB  - BACKGROUND: Receiver-operating characteristic (ROC) analysis is often applied as
      evaluation tool to compare the diagnostic validity of laboratory tests. The aim
      of this study was to draw attention to preconditions which should be taken into
      account when ROC analysis is used to assess the diagnostic performance of total
      prostate-specific antigen (tPSA) and its molecular forms in differential
      diagnosis between prostate cancer and benign prostatic hyperplasia (BPH).
      METHODS: Using a standard software (GraphROC for Windows), ROC analyses were
      performed and the areas under the curves were calculated for four hypothetical
      pairs of groups. Every group included 40 patients with prostate cancer and with
      BPH showing different tPSA concentrations (range of 2-10 microg, but similar free
      to-total PSA ratios (fPSA%). RESULTS: The area under the fPSA% ROC curve showed
      the highest value, whereas the areas under the tPSA ROC curves were dependent on
      the distributions of tPSA concentrations in the patients. The ability of fPSA% to
      improve the differential diagnosis between prostate cancer and BPH in comparison
      to tPSA was not furthermore evident, if the prostate cancer group included more
      patients with higher tPSA concentrations than the BPH group. CONCLUSIONS: When
      the diagnostic performance of tPSA and its derivatives like molecular forms in
      patients with prostate cancer and BPH should be compared by ROC analysis, a
      matching procedure is recommended prior to ROC analysis to compensate the effect
      of possible unequal tPSA distributions in both groups. Each BPH (or PCa) patient
      should be matched with a PCa (or BPH) patient with nearest tPSA concentration so
      that an optimum of overlapping tPSA concentrations in both groups can be
      achieved.

PMID- 11241552
TI  - Expression, purification, and characterization of active recombinant prostate
      specific antigen in Pichia pastoris (yeast).
AB  - BACKGROUND: Prostate-specific antigen (PSA), a member of the kallikrein family of
      serine proteases, is a chymotrypsin-like glycoprotein produced by the prostate
      epithelium. Elevated serum PSA (> 4 ng/ml) is a tumor marker for prostatic cancer
      and benign prostatic hypertrophy; increasing serum PSA over time is indicative of
      metastatic disease. It has been suggested that PSA may contribute to tumor
      metastasis through degradation of extracellular matrix glycoproteins, as well as
      cleavage of IGF binding protein-3, a modulator of IGF-1. To elucidate the role of
      PSA in the development and progression of prostatic cancer, it is necessary to
      have a reliable, cost-effective source of enzymatically active protein. Previous
      efforts to express recombinant PSA (rPSA) produced inactive proPSA, or mixtures
      of active and inactive PSA requiring activation by removal of the propeptide. We
      describe the expression of active recombinant mature PSA in yeast. METHODS:
      Stable chromosomal integration of a construct consisting of the yeast alpha
      factor signal sequence preceding the mature PSA sequence resulted in secretion of
      rPSA. The rPSA was purified from the yeast cell culture supernatant to
      homogeneity by strong cation-exchange chromatography, and characterized by SDS
      PAGE, Western analysis, electrospray mass spectrometry, N-glycanase digestion, N
      terminal amino acid sequencing, and inactivation by a PSA-specific inhibitor.
      RESULTS: We report the production of active, mature rPSA in Pichia pastoris. Two
      forms of rPSA varying slightly in glycosylation were identified. The specific
      activity of the rPSA was equal to that of human seminal plasma PSA (0.56
      micromol/min mg) as determined using a chromogenic substrate. CONCLUSIONS: Large
      scale production of active rPSA will be useful in the exploration of PSA effects
      on tumor cell proliferation, migration and metastasis. In addition, a large
      supply of enzyme should facilitate the discovery of novel inhibitors for in vitro
      and in vivo evaluation, and may provide a reproducible source of rPSA for use as
      a standard in diagnostic testing.

PMID- 11241554
TI  - Transforming growth factor beta in the human prostate: its role in stromal
      epithelial interactions in non-cancerous cell culture.
AB  - BACKGROUND: Stromal-epithelial interactions play a critical role in prostate
      development, but the precise mechanisms are still unknown. Transforming growth
      factor-beta (TGFbeta) could be a potential mediator of these interactions, but
      there is as yet no clear demonstration of its role. METHODS: Separate cultures
      and co-cultures of fibroblasts and epithelial human prostate cells were
      performed. We measured TGFbeta1 and TGFbeta2 secretion by specific ELISA assay,
      cell growth by DNA assay, and TGFbeta type II receptor expression by RT-PCR.
      RESULTS: Co-culture resulted in a 20% inhibition of epithelial cell growth,
      similar to that obtained after TGFbeta treatment (2 ng/ml for 48 hr), but without
      affecting fibroblast proliferation. This was accompanied by a five- to six-fold
      increase in epithelial TGFbeta2 secretion. CONCLUSIONS: These results demonstrate
      for the first time that TGFbeta2 secretion by prostate epithelial cells is under
      the direct control of a diffusible factor secreted by fibroblasts. They emphasize
      the role of TGFbeta in stromal-epithelial interactions.

PMID- 11241556
TI  - Activation of the orphan nuclear receptor RORalpha induces growth arrest in
      androgen-independent DU 145 prostate cancer cells.
AB  - BACKGROUND: RORalpha is a transcription factor which belongs to the family of
      orphan nuclear receptors. The regulatory functions of this receptor are still
      poorly understood. However, response elements for RORalpha are present on the
      promoter of cell cycle-related genes suggesting that it might be involved in the
      control of cell proliferation. In this study, we investigated the expression and
      the possible function of RORalpha in a human androgen-independent prostate cancer
      cell line (DU 145). The thiazolidinedione-derivative CGP 52608 has been utilized
      as the specific ligand and activator of RORalpha. METHODS: The effects of CGP
      52608 on DU 145 cell proliferation and cell cycle distribution were analyzed by
      hemocytometer and by FACS analysis, respectively. The expression of RORalpha as
      well as the effects of RORalpha activation on the expression of cell cycle
      related genes were evaluated by RT-PCR. To clarify whether RORalpha activation
      might affect the proliferation of prostate cancer cells also in vivo, nude mice
      bearing DU 145 tumor xenografts were treated with CGP 52608 at different doses
      and the growth of the tumors was followed by caliper measurement. RESULTS:
      RORalpha is expressed in DU 145 cells and the treatment of the cells with the
      thiazolidinedione-derivative CGP 52608 brought about a dose-dependent and
      significant decrease of cell proliferation. Ligand-induced activation of RORalpha
      affected cell cycle distribution, inducing an accumulation in the G(0)/G(1) phase
      and a decrease in the S phase. This effect was accompanied by an increased
      expression of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) and a
      decreased expression of cyclin A. The growth of DU 145 tumors in nude mice was
      significantly reduced by treatment with CGP 52608. CONCLUSIONS: These data
      indicate that, in androgen-independent DU 145 prostate cancer cells, activation
      of the orphan nuclear receptor RORalpha inhibits cell growth, both in vitro and
      in vivo. RORalpha also induces cell cycle arrest, possibly through the modulation
      of the expression of cell cycle-related genes.

PMID- 11241555
TI  - Long-term exposure of tumor necrosis factor alpha causes hypersensitivity to
      androgen and anti-androgen withdrawal phenomenon in LNCaP prostate cancer cells.
AB  - BACKGROUND: One of the mechanisms through which prostate cancers relapse during
      anti-androgen therapy may involve adaptation to low concentrations of androgen
      induced by anti-androgen therapies. Recent studies from our laboratory have
      reported that tumor necrosis factor-alpha (TNFalpha) is secreted from prostate
      cancer epithelial cells and LNCaP cells. We hypothesized that TNFalpha changes
      androgen-sensitivity in LNCaP cells. METHODS: We cultured LNCaP cells for more
      than 3 months in the presence of 50 ng/ml TNFalpha and established TNFalpha
      resistant LNCaP cells (LN-TR2). Sensitivity to androgen was examined by the cell
      proliferation assay. We also transfected LNCaP and LN-TR2 cells with a luciferase
      reporter plasmid driven by prostate-specific antigen (PSA) promoter and compared
      PSA promoter activity. Nuclear localization of AR protein that binds to target
      genes was also examined by Western blotting. RESULTS: LN-TR2 cells had increased
      sensitivity to dihydrotestosterone (DHT) (i.e., proliferation and PSA promoter
      activation) than LNCaP cells. Total AR mRNA and AR protein levels were decreased
      in LN-TR2 cells. However, LN-TR2 cells demonstrated increased levels of nuclear
      AR compared to LNCaP cells. At 1 nM DHT, the anti-androgen bicalutamide
      stimulated LN-TR2 and inhibited LNCaP proliferation. CONCLUSIONS: Long-term
      exposure of TNFalpha causes hypersensitivity to DHT in LNCaP and this was
      associated with increased nuclear AR protein. Furthermore, hypersensitivity to
      androgen caused anti-androgen withdrawal phenomenon in the presence of DHT
      although bicalutamide itself did not stimulate LNCaP proliferation without
      androgen. This result may be one possible mechanism for the anti-androgen
      withdrawal phenomenon.

PMID- 11241557
TI  - Prevention of lead poisoning in construction workers: a new public health
      approach.
AB  - BACKGROUND: In 1990, Yale University, the Connecticut Departments of Health
      Services and of Transportation, the Connecticut Construction Industries
      Association, and the state's construction trade unions created the Connecticut
      Road Industry Surveillance Project (CRISP). METHODS: Data from 90 bridge projects
      from 1991 to 1995 and approximately 2,000 workers were evaluated. The
      distribution of peak lead concentrations in the blood for CRISP workers
      classified into five groups were compared to that from workers outside of
      Connecticut. RESULTS: This demonstration project was instrumental in lowering
      bridge worker blood lead levels. After 1992, only the painting contract employees
      experienced peak blood lead levels with < or = 2% exceeding 50 microg/dl.
      Compared to similar workers in other states, Connecticut workers had
      significantly lower peak blood lead levels. CONCLUSIONS: Two thousand workers and
      over 120 contractors benefited directly from CRISP. Two key features of the CRISP
      model differed from the 1993 OSHA standard: a contract-specified lead health
      protection program and a centralized system of medical monitoring. These
      differences may account for the improved protection observed between the CRISP
      and non-Connecticut cohorts.

PMID- 11241558
TI  - Associations of tibia lead, DMSA-chelatable lead, and blood lead with measures of
      peripheral nervous system function in former organolead manufacturing workers.
AB  - BACKGROUND: The goals of the present study were to compare and contrast
      associations of blood lead, DMSA-chelatable lead, current tibia lead, and back
      extrapolated "peak" tibia lead with four peripheral nervous system (PNS) sensory
      and motor function measures in older males with past exposure to organic and
      inorganic lead. METHODS: Data were collected from former organolead manufacturing
      workers with an average of 16 years since last occupational lead exposure.
      Current tibia lead levels were measured by (109)Cd x-ray fluorescence. Sensory
      pressure thresholds (index and pinky fingers) and pinch and grip strength were
      measured with the Pressure-Specified Sensory Device (PSSD). RESULTS: In adjusted
      analyses, none of the four lead biomarkers was associated with sensory pressure
      threshold of the index finger or pinch or grip strength. In contrast, all four
      biomarkers were associated (P < or = 0.10) with pressure threshold of the pinky
      finger. The final linear regression models accounted for a small proportion of
      the variance in the sensory (1-3%) and motor measures (10-21%). CONCLUSIONS: This
      study found no strong association between lead biomarkers and selected PNS
      sensory or motor function measures among former organolead manufacturing workers
      with no recent occupational exposure to lead. Previously reported CNS findings in
      this cohort suggest that the PNS may be less sensitive to the chronic toxic
      effects of lead in this dose range among adults. It is also possible that the PNS
      has a greater capacity for repair than does the CNS, or that the PNS measures
      were less sensitive for detection of lead-related health outcomes than were the
      CNS measures.

PMID- 11241559
TI  - Asbestos and man-made vitreous fibers as risk factors for diffuse malignant
      mesothelioma: results from a German hospital-based case-control study.
AB  - BACKGROUND: This study examines the role of occupational factors in the
      development of diffuse malignant mesothelioma with special emphasis on the dose
      response relationship for asbestos and on the exposure to man-made vitreous
      fibers (MMVFs). METHODS: One hundred and twenty-five male cases, diagnosed by a
      panel of pathologists, were personally interviewed concerning their occupational
      and smoking history. The same number of population controls (matched for sex, age
      and region of residence) underwent similar interviews by trained interviewers.
      Odds ratios (OR) were calculated for an expert-based exposure index using
      conditional logistic regression. RESULTS: Exposure to asbestos shows the expected
      sharp gradient with an OR of about 45 for a cumulative exposure > 1.5 fiber years
      (arithmetic mean 16 fiber years). A significant OR was calculated even for the
      lowest exposure category "> 0 - < or = 0.15 fiber years". Although the mean
      cumulative exposure to MMVF is roughly 10% of the exposure to asbestos, an
      increased OR is observed in an ever/never evaluation. This observation is heavily
      hampered by methodical problems. A corresponding case-control study was performed
      using a lung tissue fiber analysis in addition to interviews. Both interviews and
      the lung tissue analysis yielded similar OR levels between the reference and the
      maximum exposure intervals. CONCLUSIONS: Despite a possible influence as a result
      of selection and information bias, our results confirm the previously reported
      observation of a distinct dose-response relationship even at levels of cumulative
      exposure below 1 fiber year. Moreover, the study confirms that asbestos is a
      relevant confounder for MMVF. A causal relationship between exposure to MMVF and
      mesothelioma could neither be detected nor excluded, as in other studies.

PMID- 11241560
TI  - Breast cancer, occupation, and exposure to electromagnetic fields among Swedish
      men.
AB  - BACKGROUND: Investigations of breast cancer among men may provide clues for
      environmental and occupational risk factors that may be difficult to study in
      women, because of confounding or effect modification from reproductive female
      characteristics. The objective was to estimate occupation-specific risks of male
      breast cancer and to assess the effect of occupational exposure to extremely low
      frequency magnetic fields (ELFMF). METHODS: Standardized incidence ratios were
      computed for the period 1971-1989 among Swedish men who were 25-59 years of age
      at start of follow-up and gainfully employed in 1970. Log-linear Poisson models
      were fitted to adjust for geographical area. A job exposure matrix was used to
      classify occupational ELFMF exposure. RESULTS: A marked and consistent excess
      risk was found for machinery repairers. Increased relative risks based on few
      cases were also noted for librarians/archivists/curators, bank employees, non
      specified clerical workers, metal processing workers, tanners/fur dressers,
      policemen, and custom surveillance officials. The relative risk among subjects
      with an estimated ELFMF exposure above the first quartile (0.12 microT) was 1.31
      (95% confidence interval = 0.94-1.81), without a clear exposure-response pattern.
      Indications of an exposure-response relationship were found in workers with
      intermittent ELFMF exposure. CONCLUSIONS: The findings give no clear evidence for
      an etiological role of ELFMF in the development of breast cancer in men, but
      suggest that large variations in exposure over the work-day may be associated
      with an increased risk.

PMID- 11241561
TI  - Polymorphisms of the IL-1 gene complex in coal miners with silicosis.
AB  - BACKGROUND: Silicosis is characterized by fibrosing nodular lesions that
      eventually develop into progressive pulmonary fibrosis. Pro-inflammatory
      cytokines, such as interleukin-1 (IL-1), play a key role in the development of
      silicosis by regulating mediators which are responsible for lung injury,
      inflammation, and potentially fibrosis. To study whether functional single
      nucleotide polymorphisms (SNPs) located in the regulatory elements of genes
      coding for the IL-1alpha, IL-1beta, and IL-1 receptor antagonist (RA) cytokines
      are associated with silicosis, we examined 318 Caucasian cases confirmed
      histopathologically with pulmonary silicosis and 163 controls without any
      apparent inflammation or other pulmonary disease. METHODS: Genotyping was carried
      out by polymerase chain reaction-restriction fragment length polymorphism
      technique. RESULTS: The proportion of the IL-1RA (+ 2018) allele 2 genotype was
      increased in miners with silicosis (0.27) compared to controls (0.16). The odds
      of being a case were 2.15 (CI = 1.4-3.3) times higher for subjects with at least
      one copy of allele 2. No statistically significant differences in the allelic
      frequencies or genotype distributions for IL-1alpha (+ 4845) or IL-1beta (+ 3953)
      were found between the control and disease groups. CONCLUSIONS: This is the first
      report showing an association between the IL-1RA (+ 2018) polymorphism and
      silicosis, and suggests that this polymorphism may confer increased risk for the
      development of the disease.

PMID- 11241562
TI  - Work-related respiratory symptoms in New Zealand farmers.
AB  - BACKGROUND: The first national survey of the respiratory health of New Zealand
      farmers looked at the prevalence of respiratory symptoms by farm type and work
      exposure. METHODS: An 8-page questionnaire was mailed to 2,203 farmers randomly
      selected from all over New Zealand. RESULTS: Response rate was 77.6% of 2,203, or
      1,706 participants. Breathing problems at work were reported by 17.6% of farmers.
      Working with oats was strongly associated with work-related breathing problems
      (OR = 3.3, 2.1-5.2). Dyspnea was more common in female farmers, whereas chronic
      bronchitis was higher in males. Orchardists (OR = 2.3, 1.3-4.0), those growing
      oat crops (OR = 3.0, 1.7-5.4) and using the grain mill (OR = 2.8, 1.3-6.3)
      reported the highest symptom rates of ODTS/FL. Having hay fever or eczema, and
      smoking were risk factors for all respiratory symptoms. CONCLUSIONS: Working in
      the areas of pigs, poultry, horses, grains, and hay are associated with
      respiratory symptoms in New Zealand farmers.

PMID- 11241563
TI  - Identifying high-risk small business industries for occupational safety and
      health interventions.
AB  - BACKGROUND: Approximately one-third (32%) of U.S. workers are employed in small
      business industries (those with 80% of workers in establishments with fewer than
      100 employees), and approximately 53 million persons in private industry work in
      small business establishments. This study was performed to identify small
      business industries at high risk for occupational injuries, illnesses, and
      fatalities. METHODS: Small business industries were identified from among all
      three- and four-digit Standard Industrial Classification (SIC) codes and ranked
      using Bureau of Labor Statistics (BLS) data by rates and numbers of occupational
      injuries, illnesses, and fatalities. Both incidence rates and number of injury,
      illness, and fatality cases were evaluated. RESULTS: The 253 small business
      industries identified accounted for 1,568 work-related fatalities (34% of all
      private industry). Transportation incidents and violent acts were the leading
      causes of these fatalities. Detailed injury and illness data were available for
      105 small business industries, that accounted for 1,476,400 work-related
      injuries, and 55,850 occupational illnesses. Many of the small business
      industries had morbidity and mortality rates exceeding the average rates for all
      private industry. The highest risk small business industries, based on a combined
      morbidity and mortality index, included logging, cut stone and stone products,
      truck terminals, and roofing, siding, and sheet metal work. CONCLUSIONS:
      Identification of high-risk small business industries indicates priorities for
      those interested in developing targeted prevention programs.

PMID- 11241564
TI  - Mechanisms of occupational injuries reported to insurance companies in Norway
      from 1991 to 1996.
AB  - BACKGROUND: To study the association of injury events, types of movements and
      types of objects involved in relation to occupation, age, and gender in serious
      occupational injuries to determine where preventive measures should be
      implemented. METHODS: The occupational injury claims made to the insurance
      companies in Norway for 1991-1996, which were stored in a database, were
      analyzed. RESULTS: Falls were the most frequent injury event in both genders and
      in all occupational groups, and the incidence rate increased with age. Among men,
      the most common action when the injury occurred was handling of goods or
      materials, whereas for women it was moving without goods or materials. Primary
      economic activity and manufacturing had the highest injury rates. CONCLUSIONS:
      Priority should be given to reduce the occurrence of falls in both genders, and
      especially among older workers.

PMID- 11241565
TI  - Urinary concentrations of trichloroacetic acid in Danish workers exposed to
      trichloroethylene, 1947-1985.
AB  - BACKGROUND: Since 1947, the National Labour Inspection Service in Denmark has
      relied upon urinary measurements of trichloroacetic acid (TCA) in surveys of the
      occupational exposure to trichloroethylene (TCE). METHODS: We examined the paper
      files relating to 2397 TCA measurements to extract information about the year,
      the company, the work process and the worker. We used multiple regression models
      to analyze the effects of various factors on the urinary concentration of TCA.
      RESULTS: The regression analyses showed that (1) a four-fold decrease in TCA
      concentrations occurred from 1947 to 1985; (2) the highest concentrations were
      observed in the iron and metal, chemical, and dry cleaning industries; (3) TCA
      levels were two times higher among men compared with women in the iron and metal
      and dry cleaning industries; (4) TCA concentrations were higher among younger
      compared with older workers; and (5) persons working in an area in which TCE was
      used, but not working with TCE themselves, also showed urinary TCA levels
      indicative of exposure. CONCLUSIONS: Calendar year, type of industry, degree of
      contact with TCE, sex and age were predictors of TCA concentration in the urine
      of Danish workers.

PMID- 11241566
TI  - Prevalence and risk factors of tendinitis and related disorders of the distal
      upper extremity among U.S. workers: comparison to carpal tunnel syndrome.
AB  - BACKGROUND: National estimates of tendinitis and related disorders of the distal
      upper extremity among U.S. workers have not been available with the exception of
      carpal tunnel syndrome. METHODS: The Occupational Health Supplement Data of the
      1988 National Health Interview Survey were analyzed for tendinitis and related
      disorders of the hand/wrist and elbow (distal upper extremity) using the Survey
      Data Analysis (SUDAAN) software. RESULTS: Among the 30,074 respondents
      (statistically weighted population of 127 million) who had worked anytime during
      the previous 12 months, 0.46% (95% CI: 0.36, 0.56) reported that they experienced
      a "prolonged" hand discomfort which was called tendinitis, synovitis,
      tenosynovitis, deQuervain's disease, epicondylitis, ganglion cyst, or trigger
      finger, by a medical person. This corresponds to 588,000 persons (95% CI:
      457,000; 712,000) reporting one of these disorders, 28% (or 164,000) of which
      were thought to be work-related by the medical person. Among various risk factors
      examined by multiple logistic regression analysis, bending/twisting of the
      hands/wrists at work and female gender were significantly associated with
      reporting of these disorders. CONCLUSIONS: By combining these cases with the
      previously reported cases of work-related carpal tunnel syndrome, we estimate
      that there were approximately 520,000 cases of work-related musculoskeletal
      disorders of the distal upper extremity among US workers in 1988.

PMID- 11241568
TI  - Re: Researchers should talk to workers. Am. J. Ind. Med. 2000. 37:668.

PMID- 11241567
TI  - A review and meta-analysis of formaldehyde exposure and pancreatic cancer.
AB  - BACKGROUND: Most reviews on the carcinogenicity of formaldehyde have focused on
      cancers of the respiratory tract. Two recent studies have suggested that exposure
      to formaldehyde may increase the risk for pancreatic cancer. METHODS: We examine
      14 epidemiology studies of workers exposed to formaldehyde where pancreatic
      cancer rates were reported and use meta-analytic techniques to summarize the
      findings. We also rank formaldehyde exposures for the industries in these
      studies. RESULTS: We found a small increase of pancreatic cancer risk in the
      studies overall (meta Relative Risk [mRR] 1.1, 95%CI 1.0-1.3); however, this
      increased risk was limited to embalmers (mRR 1.3, 95%CI 1.0-1.6) and pathologists
      and anatomists (mRR 1.3, 95%CI 1.0-1.7). There was no increased risk among
      industrial workers (mRR 0.9, 95%CI 0.8-1.1) who on average had the highest
      formaldehyde exposures. CONCLUSIONS: A small increased risk of pancreatic cancer
      from formaldehyde exposure cannot be ruled out from the studies examined.
      However, the null findings among industrial workers and the lack of biological
      plausibility would argue against formaldehyde as a cause. The increased risk of
      pancreatic cancer among embalmers, pathologists, and anatomists may be due to a
      diagnostic bias or to occupational exposures other than formaldehyde in these
      professions.

PMID- 11241570
TI  - Competing risks analysis of patients with osteosarcoma: a comparison of four
      different approaches.
AB  - In failure time studies involving a chronic disease such as cancer, several
      competing causes of mortality may be operating. Commonly, the conventional
      statistical technique of Kaplan-Meier, which is only meaningfully interpreted by
      assuming independence of failure types and the censoring mechanism, is employed
      in clinical research involving competing risks data. Some authors have advocated
      the use of a cause-specific cumulative incidence function which takes into
      account the existence of other events within a competing risks framework, without
      making any assumption about independence. Lunn and McNeil have proposed an
      approach based on an extension of the Cox proportional hazards regression, which
      enables direct comparisons between failure types. We have extended this approach
      to estimate cause-specific cumulative incidence. As it is often not easy to
      follow competing risks methodology in the literature, this paper sets out
      systematically the assumptions made and the steps taken to implement four
      different methods of analysing competing risks data using cumulative incidence
      rates or the Kaplan-Meier estimates of cause-specific failure probabilities. The
      data obtained from a randomized trial of patients with osteosarcoma were used to
      compare these four approaches. As illustrated using the osteosarcoma data, the
      estimates of the classical Kaplan-Meier methods have larger numerical values than
      the cause-specific cumulative incidence. On the other hand, estimates of the
      cause-specific cumulative incidence rates from the conventional method and the
      modified Cox method are highly comparable.

PMID- 11241571
TI  - Multilevel growth curve models with covariate effects: application to recovery
      after stroke.
AB  - In measuring the progression of, or recovery from, a disease an individual's
      outcome may be assessed on a number of occasions. A model of the relationship
      between outcome and time since disease occurred which accounts for patient
      characteristics could be used to describe patterns of recovery, to predict
      outcome for a patient, or to evaluate health interventions. We use multilevel
      models to analyse such data, focusing on the choice of powers of time both for
      mean outcome and covariate effects. We give equations for predicted outcome and
      corresponding standard errors (i) based only on baseline characteristics, and
      (ii) by conditioning on previous outcomes for an individual. In a study of 331
      stroke patients, outcome was measured approximately 0, 2,4,6 and 12 months after
      stroke. Patient characteristics included age, sex, and pre-stroke handicap,
      together with stroke-severity indicators (presence of limb deficit, dysphasia,
      dysarthria or incontinence). Of these, only the effects of age, dysphasia and
      presence of deficit varied with time. Conditioning on previous observations
      improved the accuracy of predictions. The outcome variable clearly had a skewed
      distribution, and the model residuals showed evidence of non-Normality. We
      discuss alternative models for non-Normal data, and show that, here, the standard
      (Normal errors) multilevel model gives equivalent parameter estimates and
      predictions to those obtained from alternative models.

PMID- 11241572
TI  - Efficiency comparisons of rank and permutation tests based on summary statistics
      computed from repeated measures data.
AB  - A popular method of using repeated measures data to compare treatment groups in a
      clinical trial is to summarize each individual's outcomes with a scalar summary
      statistic, and then to perform a two-group comparison of the resulting statistics
      using a rank or permutation test. Many different types of summary statistics are
      used in practice, including discrete and continuous functions of the underlying
      repeated measures data. When the repeated measures processes of the comparison
      groups differ by a location shift at each time point, the asymptotic relative
      efficiency of (continuous) summary statistics that are linear functions of the
      repeated measures has been determined and used to compare tests in this class.
      However, little is known about the non-null behaviour of discrete summary
      statistics, about continuous summary statistics when the groups differ in more
      complex ways than location shifts or where the summary statistics are not linear
      functions of the repeated measures. Indeed, even simple distributional structures
      on the repeated measures variables can lead to complex differences between the
      distribution of common summary statistics of the comparison groups. The presence
      of left censoring of the repeated measures, which can arise when these are
      laboratory markers with lower limits of detection, further complicates the
      distribution of, and hence the ability to compare, summary statistics. This paper
      uses recent theoretical results for the non-null behaviour of rank and
      permutation tests to examine the asymptotic relative efficiencies of several
      popular summary statistics, both discrete and continuous, under a variety of
      common settings. We assume a flexible linear growth curve model to describe the
      repeated measures responses and focus on the types of settings that commonly
      arise in HIV/AIDS and other diseases.

PMID- 11241573
TI  - Bayesian cost-effectiveness analysis from clinical trial data.
AB  - A key tool for assessing the relative cost-effectiveness of two treatments in
      health economics is the incremental C/E acceptability curve. We present Bayesian
      computations for this curve in the case where data on both costs and efficacy are
      available from a clinical trial. Analysis is given under various formulations of
      prior information. A case study is analysed in which reasonable prior information
      is shown to strengthen substantially the posterior inference, leading to a more
      conclusive assessment of cost-effectiveness. Calculations can be performed using
      readily available Bayesian software.

PMID- 11241574
TI  - Bayesian analyses of longitudinal binary data using Markov regression models of
      unknown order.
AB  - We present non-homogeneous Markov regression models of unknown order as a means
      to assess the duration of autoregressive dependence in longitudinal binary data.
      We describe a subject's transition probability evolving over time using logistic
      regression models for his or her past outcomes and covariates. When the initial
      values of the binary process are unknown, they are treated as latent variables.
      The unknown initial values, model parameters, and the order of transitions are
      then estimated using a Bayesian variable selection approach, via Gibbs sampling.
      As a comparison with our approach, we also implement the deviance information
      criterion (DIC) for the determination of the order of transitions. An example
      addresses the progression of substance use in a community sample of n = 242
      American Indian children who were interviewed annually four times. An extension
      of the Markov model to account for subject-to-subject heterogeneity is also
      discussed.

PMID- 11241575
TI  - Exposure misclassification: bias in category specific Poisson regression
      coefficients.
AB  - In epidemiologic studies of the association between exposure and disease,
      misclassification of exposure is common and known to induce bias in the effect
      estimates. The nature of the bias is difficult to foretell. For this purpose, we
      present a simple method to assess the bias in Poisson regression coefficients for
      a categorical exposure variable subject to misclassification. We derive
      expressions for the category specific coefficients from the regression on the
      error-prone exposure (naive coefficients) in terms of the coefficients from the
      regression on the true exposure (true coefficients). These expressions are
      similar for crude and adjusted models, if we assume that the covariates are
      measured without error and that it is independence between the misclassification
      probabilities and covariate values. We find that the bias in the naive
      coefficient for one category of the exposure variable depends on all true
      category specific coefficients weighted by misclassification probabilities. On
      the other hand, misclassification of an exposure variable does not induce bias in
      the estimates of the coefficients of the (perfectly measured) covariates.
      Similarities with linear regression models are pointed out. For selected
      scenarios of true exposure-disease associations and selected patterns of
      misclassification, we illustrate the inconsistency in naive Poisson regression
      coefficients and show that it can be difficult to intuitively characterize the
      nature of the bias. Both the magnitude and the direction of the bias may vary
      between categories of an exposure variable.

PMID- 11241576
TI  - Tests for 2 x K contingency tables with clustered ordered categorical data.
AB  - Ordered categorical data summarized in a 2 x K table usually consist of two
      sample multinomial or K-sample binomial observations. In analysing these data, we
      usually assign scores to the K columns and perform a testing for the equality of
      two multinomial distributions in the former case and no trend among K binomial
      proportions in the latter case. Among the most popular score tests are the
      Wilcoxon rank sum test and the Armitage's linear trend test. In this paper we
      extend the score tests to be used for clustered data under diverse study designs.
      Our methods do not require correct specification of the dependence structure
      within clusters. The proposed tests are based on the asymptotic normality for
      large number of clusters and are a generalization of the standard tests used for
      independent data. Simulation studies are conducted to investigate the finite
      sample performance of the new methods. The proposed methods are applied to real
      life data.

PMID- 11241577
TI  - Methods for estimating the AIDS incubation time distribution when date of
      seroconversion is censored.
AB  - In most cohort studies on HIV infection and AIDS, data on time from
      seroconversion to AIDS or death are doubly censored, both at the time origin and
      at the endpoint of interest. In epidemiological research, the most frequently
      adopted approach is to restrict the analysis to persons with narrow
      seroconversion intervals and to impute the midpoint of this interval as date of
      seroconversion. For many cohort studies, the consequence is that a substantial
      proportion of the data is not used. We consider four methods that are expected to
      be less biased when all cohort data are used: two imputation methods, conditional
      mean and multiple imputation, and two likelihood maximization methods. We derive
      the likelihood structure of the cohort data and clarify its dependence on study
      design. All methods are applied to data from the Amsterdam cohort study among
      injection drug users. In a simulation study the data generation process of this
      cohort study is imitated. The performance of midpoint, conditional mean and
      multiple imputation are compared. With midpoint imputation, both an analysis
      using the full data set, as well as one restricted to the cases with small
      seroconversion intervals, is performed. Conditional mean imputation comes out as
      the preferred method. It gives best results with respect to mean squared error.
      Moreover, when confidence intervals are computed through standard methods that
      ignore the uncertainty in the imputed date of seroconversion, coverage
      probabilities are almost correct.

PMID- 11241578
TI  - Optimum biased-coin designs for sequential treatment allocation with covariate
      information by A. C. Atkinson, Statistics in Medicine 1999; 18:1741-1752.

PMID- 11241580
TI  - Glial transporters for glutamate, glycine and GABA I. Glutamate transporters.
AB  - The termination of chemical neurotransmission in the CNS involves the rapid
      removal of neurotransmitter from synapses by specific transport systems. Such
      mechanism operates for the three major amino acid neurotransmitters glutamate,
      gamma-aminobutyric acid (GABA) and glycine. To date, five different high-affinity
      Na(+)-dependent glutamate (Glu) transporters have been cloned: GLT1, GLAST,
      EAAC1, EAAT4 and EAAT5. The first two are expressed mainly by glial cells, and
      seem to be the predominant Glu transporters in the brain. A major function of Glu
      uptake in the nervous system is to prevent extracellular Glu concentrations from
      raising to neurotoxic levels in which glial transporters seem to play a critical
      role in protecting neurons from glutamate-induced excitotoxicity. Under
      particular conditions, glial GluTs have been shown to release Glu by reversal of
      activity, in a Ca(2+)--and energy-independent fashion. Furthermore, an activity
      of these transporters as ion channels or transducing units coupled to G-proteins
      has recently been reported. The localization, stoichiometry, and regulation of
      glial GluTs are outlined, as well as their possible contributions to nervous
      system diseases as ALS, AD and ischemic damage.

PMID- 11241581
TI  - Glial transporters for glutamate, glycine, and GABA: II. GABA transporters.
AB  - The termination of chemical neurotransmission in the central nervous system (CNS)
      involves the rapid removal of neurotransmitter from synapses. This is fulfilled
      by specific transport systems in neurons and glia, including those for gamma
      aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain.
      Glial cells express the cloned Na(+)/Cl(-)-dependent, high-affinity GABA
      transporters (GATs) GAT1, GAT2, and GAT3, as well as the low-affinity transporter
      BGT1. In situ hybridization and immunocytochemistry have revealed that each
      transporter shows distinct regional distribution in the brain and the retina. The
      neuronal vs. glial localization of the different transporters is not clear-cut,
      and variations according to species, neighboring excitatory synapses, and
      developmental stage have been reported. The localization, stoichiometry, and
      regulation of glial GATs are outlined, and the participation of these structures
      in development, osmoregulation, and neuroprotection are discussed. A decrease in
      GABAergic neurotransmission has been implicated in the pathophysiology of several
      CNS disorders, particularly in epilepsy. Since drugs which selectively inhibit
      glial but not neuronal GABA uptake exert anticonvulsant activity, clearly the
      establishment of the molecular mechanisms controlling GATs in glial cells will be
      an aid in the chemical treatment of several CNS-related diseases.

PMID- 11241582
TI  - c-Jun regulation in rat neonatal motoneurons postaxotomy.
AB  - Motoneurons respond to peripheral nerve transection by either regenerative or
      degenerative events depending on their state of maturation. Since the expression
      of c-Jun has been involved in the early signalling of the regenerative process
      that follows nerve transection in adults, we have investigated c-Jun on rat
      neonatal axotomized motoneurons during the period in which neuronal death is
      induced. Changes in levels of c-Jun protein and its mRNA were determined by means
      of quantitative immunocytochemistry and in situ hybridization. Three hours after
      nerve transection performed on postnatal day (P)3, c-Jun protein and mRNA is
      induced in axotomized spinal cord motoneurons, and high levels were reached
      between 1 and 10 days after. This response is associated with a detectable c-Jun
      activation by phosphorylation on serine 63. No changes were found in the levels
      of activating transcription factor -2. Most of dying motoneurons were not
      labelled by either a specific c-Jun antibody or a c-jun mRNA probe. However,
      dying motoneurons were specifically stained by a polyclonal anti c-Jun antibody,
      indicating that some c-Jun antibodies react with unknown epitopes, probably
      distinct from c-Jun p39, that are specifically associated with apoptosis.

PMID- 11241583
TI  - Identification of the amino acids on a neuronal glutamate receptor recognized by
      an autoantibody from a patient with paraneoplastic syndrome.
AB  - Autoantibodies from a patient with paraneoplastic disease were identified
      previously to bind to the glutamate receptor (GluR) subunit GluR5 and to function
      as potential allosteric modulators of receptor activity (Gahring et al. [1995]
      Mol Med 1:245-253). In the present study we have used deletion mapping and
      mutagenesis to define the residues in GluR5 bound by this autoreactivity. The
      autoantibody contact residues include residues K497, N508, K510, E512, and to a
      lesser extent Q507. Residues 507-512 confer autoantibody specificity of the
      autoreactivity to GluR5. These residues have been shown in crystallographic
      studies (Armstrong et al. [1998] Nature 395:913-917) to participate in a loop
      structure, whereas residue K497 is located on a beta-strand. Notably, this
      binding spans tyrosine 504, a residue important in forming the agonist-binding
      site. We propose that autoantibody binding of essential residues in this GluR5
      autoantigenic region defines a subunit-specific allosteric regulatory site on
      neuronal glutamate receptors and suggests how receptor dysfunction and region
      specific neuronal death in the brain can progress in certain autoimmune
      neurological diseases.

PMID- 11241584
TI  - Neurite growth promotion by nerve growth factor and insulin-like growth factor-1
      in cultured adult sensory neurons: role of phosphoinositide 3-kinase and mitogen
      activated protein kinase.
AB  - Although neurons of the PNS no longer require neurotrophins such as Nerve Growth
      Factor (NGF) for their survival, such factors are involved in regulating axonal
      sprouting and regeneration after injury. In addition to the neurotrophin
      receptors, sensory neurons are reported to express IGF-1, EGF and FGF receptors.
      To investigate the influence of growth factors in addition to NGF, we examined
      the effects of IGF-1 EGF and FGF on neurite growth from adult rat dorsal root
      ganglion sensory neurons in both dissociated cultures and in compartmented
      cultures. As expected, NGF elicited robust neuritic growth in both the
      dissociated and compartmented cultures. The growth response to IGF-1 was similar,
      although there was minimal neurite growth in response to EGF or FGF. In addition,
      IGF-1 (but neither FGF nor EGF), when applied to cell bodies in compartmented
      cultures, potentiated the distal neurite growth into NGF-containing side
      compartments. This potentiation was not seen when these factors were provided
      along with NGF in the side compartments of compartmented cultures, or in the
      dissociated cultures. To determine the contribution of signaling intermediates
      downstream of receptor activation, we used inhibitors of the potential effectors
      and Western blotting. The PI 3-kinase inhibitor, LY294002 attenuated neurite
      growth evoked by NGF, IGF and EGF in dissociated cultures, although the MAP
      kinase kinase (MEK) inhibitor PD098059 diminished the growth in only IGF.
      Immunoprecipitation and Western blotting results demonstrated differential
      activation of MAPK, PI 3-kinase, PLCgamma1 and SNT by the different factors.
      Activation of PI 3-kinase and SNT by both NGF and IGF-1 correlated with their
      effects on neurite growth. These results support the hypothesis that the PI 3
      kinase pathway plays an important role in neuritogenesis.

PMID- 11241585
TI  - Hypoxanthine impairs morphogenesis and enhances proliferation of a neuroblastoma
      model of Lesch Nyhan syndrome.
AB  - Extracellular purines have essential roles in neuronal development; hence,
      disruptions in their metabolism as reported in Lesch Nyhan syndrome (LNS) could
      result in developmental abnormalities. The deficiency of hypoxanthine-guanine
      phosphoribosyl transferase (HGPRT) in LNS leads to increased hypoxanthine and
      uric acid production. We have reported that HGPRT-deficient B103-4C
      neuroblastoma, a neuronal model of LNS, proliferated less and differentiated more
      than their HGPRT-positive B103 counterparts. Here, we sought to determine whether
      differences in proliferation and differentiation would occur when these cells
      were cultured in the presence of hypoxanthine or in a hypoxanthine-/serum-free
      chemically defined media (NBMN2). In media with 1% serum, hypoxanthine (50
      microM) significantly increased the proliferation of both cell lines with a
      greater effect on B103-4C cells. In 1% serum media, hypoxanthine increased
      differentiation of B103 but decreased B103-4C differentiation. In NBMN2, B103
      proliferated far more than B103-4C, but both cell types differentiated to the
      same extent. These results are interpreted to suggest that elevated levels of
      central nervous system (CNS) hypoxanthine as reported in LNS may affect neuronal
      development, and to implicate hypoxanthine and abnormal neuronal development as
      causative factors in the etiology of LNS.

PMID- 11241586
TI  - Ginsenoside Rb1 and Rg1 improve spatial learning and increase hippocampal
      synaptophysin level in mice.
AB  - We investigated the cognition enhancing effects of ginsenoside Rb1 and Rg1. Mice
      were trained in a Morris water maze following injection (i.p.) of Rb1 (1 mg/kg)
      or Rg1 (1 mg/kg) for 4 days. Both Rb1- and Rg1-injected mice showed enhanced
      spatial learning compared to control animals. The hippocampus, but not the
      frontal cortex, of treated mice contained higher density of a synaptic marker
      protein, synaptophysin, compared to control mice. Electrophysiological recordings
      in hippocampal slices revealed that Rb1 or Rg1 injection did not change the
      magnitude of paired-pulse facilitation or long-term potentiation. Our results
      suggest that Rb1 and Rg1 enhance spatial learning ability by increasing
      hippocampal synaptic density without changing plasticity of individual synapses.

PMID- 11241587
TI  - Modification of representational difference analysis applied to the isolation of
      forskolin-regulated genes from Schwann cells.
AB  - Many aspects of the response of Schwann cells to axonal cues can be induced in
      vitro by the adenylyl cyclase activator forskolin, yet the role of cAMP signaling
      in regulating Schwann cell differentiation remains unclear. To define better the
      relationship between cAMP signaling and Schwann cell differentiation, we used a
      modification of cDNA representational difference analysis (RDA) that permits the
      analysis of small amounts of mRNA and identified additional genes that are
      differentially expressed by forskolin-treated and untreated Schwann cells. The
      genes that we have identified, including MKP3, a regulator of ERK signaling, and
      the sphingosine-1-phosphate receptor edg3/lp(B3), may play important roles in
      mediating Schwann cell differentiation.

PMID- 11241590
TI  - From Glycals to Glycopeptides: A Convergent and Stereoselective Total Synthesis
      of a High Mannose N-Linked Glycopeptide This work was supported by the National
      Institutes of Health (Grant Numbers AI16943/CA28824). We thank Dr. George
      Sukenick of the MSKCC NMR Core Facility for NMR and mass spectral analyses (NIH
      Grant Number: CA08748). 

PMID- 11241588
TI  - Distribution in ocular structures and optic pathways of immunocompetent and glial
      cells in an experimental allergic encephalomyelitis (EAE) relapsing model.
AB  - Relapsing experimental allergic encephalomyelitis (EAE) was induced in DA rats
      and the ocular pathologic events were examined at the various phases of the
      illness. About 80% of EAE rats presented anterior uveitis (AU), even after
      complete EAE recovery. We studied the phenotype and localization of
      immunocompetent cells, the major histocompatibility complex (MHC) class I and II
      antigen expression, as well as the chemokine monocyte chemoattractant protein-1
      (MCP-1) appearance. In control animals, there were many glial fibrillary acidic
      protein (GFAP)(+) cells and OX42(+) cells in the ciliary body, retina, optic
      nerve and chiasma. Except in retina, we observed constitutive MHC class I and II
      expression. During the EAE acute phase, there was up-regulation of MHC class II
      and GFAP antigens in iris, ciliary body, limbus, and optic pathways. MHC class I
      and ED2 antigens were expressed in meninges and in the prechiasmatic cisterna, by
      cells which could have a role in immune surveillance. MCP-1 mRNA was highly
      expressed in optic pathways during the acute phase and the protein was expressed
      by astrocytes, macrophages, and lymphocytes. During the relapsing phase, MCP-1
      was weakly expressed to disappear almost completely during the final recovery
      phase. The expression of MHC class II on astrocytes was increased during the
      relapsing and final recovery phase in which the inflammatory lesions persisted.
      These findings suggest that ocular areas and optic pathways, mainly optic
      chiasma, are important targets in the relapsing EAE.

PMID- 11241591
TI  - The High-Valent Compound of Cytochrome P450: The Nature of the Fe-S Bond and the
      Role of the Thiolate Ligand as an Internal Electron Donor This research was
      sponsored in part by the Israeli Science Foundation (ISF) and the Binational
      German-Israeli Foundation (GIF). F.O. thanks the EU for a Marie Curie Fellowship.

PMID- 11241592
TI  - The Synthesis of CP-263,114 and CP-225,917: Striking Long-Range Stereocontrol in
      the Fashioning of C7 Financial support was provided by the National Institutes of
      Health (Grant nos. CA-28824 and HL-25848 for S.J.D., CA-08748 for the Sloan
      Kettering Institute Core Facility). Q.T. gratefully acknowledges the US
      Department of Defense for a postdoctoral fellowship (U.S. Army grant no. DAMD-17
      99-1-9373). We thank the Pfizer Corporation, particularly Dr. T. Kaneko and Dr.
      T. T. Dabrah for discussions and for providing valuable CP samples from
      fermentation broth. We are grateful to Dr. Dongfang Meng for his major
      contributions to this work. We also thank George Sukenick of the Sloan-Kettering
      Institute Core Facility for mass spectral analyses and assistance in NMR
      spectroscopic and HPLC analyses, and Sylvi Rusli for mass spectral analyses. 

PMID- 11241593
TI  - Kinetic Resolution of Amines by a Nonenzymatic Acylation Catalyst We thank
      Michael M.-C. Lo, Dr. J. Craig Ruble, and Beata Tao for helpful discussions and
      preliminary studies, and we also thank Dr. George P. Luke (ARIAD Pharmaceuticals,
      Inc.) for providing the primary amine illustrated in entry 8 of Table 1. Support
      has been provided by Bristol-Myers Squibb, Merck, the National Institutes of
      Health (National Institute of General Medical Sciences, R01-GM57034), Novartis,
      Pfizer, and Pharmacia. 

PMID- 11241594
TI  - Functionalized Polymers-Emerging Versatile Tools for Solution-Phase Chemistry and
      Automated Parallel Synthesis.
AB  - As part of the dramatic changes associated with the need for preparing compound
      libraries in pharmaceutical and agrochemical research laboratories, industry
      searches for new technologies that allow for the automation of synthetic
      processes. Since the pioneering work by Merrifield polymeric supports have been
      identified to play a key role in this field however, polymer-assisted solution
      phase synthesis which utilizes immobilized reagents and catalysts has only
      recently begun to flourish. Polymer-assisted solution-phase synthesis has various
      advantages over conventional solution-phase chemistry, such as the ease of
      separation of the supported species from a reaction mixture by filtration and
      washing, the opportunity to use an excess of the reagent to force the reaction to
      completion without causing workup problems, and the adaptability to continuous
      flow processes. Various strategies for employing functionalized polymers
      stoichiometrically have been developed. Apart from reagents that are covalently
      or ionically attached to the polymeric backbone and which are released into
      solution in the presence of a suitable substrate, scavenger reagents play an
      increasingly important role in purifying reaction mixtures. Employing
      functionalized polymers in solution-phase synthesis has been shown to be
      extremely useful in automated parallel synthesis and multistep sequences. So far,
      compound libraries containing as many as 88 members have been generated by using
      several polymer-bound reagents one after another. Furthermore, it has been
      demonstrated that complex natural products like the alkaloids (+/-)-oxomaritidine
      and (+/-)-epimaritidine can be prepared by a sequence of five and six consecutive
      polymer-assisted steps, respectively, and the potent analgesic compound (+/-)
      epibatidine in twelve linear steps ten of which are based on functionalized
      polymers. These developments reveal the great future prospects of polymer
      assisted solution-phase synthesis.

PMID- 11241595
TI  - Hemilability of Hybrid Ligands and the Coordination Chemistry of Oxazoline-Based
      Systems.
AB  - Ligand design is becoming an increasingly important part of the synthetic
      activity in chemistry. This is of course because of the subtle control that
      ligands exert on the metal center to which they are coordinated. Ligands which
      contain significantly different chemical functionalities, such as hard and soft
      donors, are often called hybrid ligands and find increasing use in molecular
      chemistry. Although the interplay between electronic and steric properties has
      long been recognized as essential in determining the chemical or physical
      properties of a complex, predictions remain very difficult, not only because of
      the considerable diversity encountered within the Periodic Table-different metal
      centers will behave differently towards the same ligand and different ligands can
      completely modify the chemistry of a given metal-but also because of the small
      energy differences involved. New systems may-even through serendipity-allow the
      emergence of useful concepts that can gain general acceptance and help design
      molecular structures orientated towards a given property. The concept of ligand
      hemilability, which finds numerous illustrations with hybrid ligands, has gained
      increased acceptance and been found to be very useful in explaining the
      properties of metal complexes and in designing new systems for molecular
      activation, homogeneous catalysis, functional materials, or small-molecule
      sensing. In the field of homogeneous enantioselective catalysis, in which steric
      and/or electronic control of a metal-mediated process must occur in such a way
      that one stereoisomer is preferentially formed, ligands containing one or more
      chiral oxazoline units have been found to be very valuable for a wide range of
      metal-catalyzed reactions. The incorporation of oxazoline moieties in
      multifunctional ligands of increasing complexity makes such ligands good
      candidates to display hemilabile properties, which until recently, had not been
      documented in oxazoline chemistry. Herein, we briefly recall the definition and
      scope of hemilabile ligands, present the main classes of ligands containing one
      or more oxazoline moieties, with an emphasis on hybrid ligands, and finally
      explain why the combination of these two facets of ligand design appears
      particularly promising.

PMID- 11241596
TI  - Does CIP Nomenclature Adequately Handle Molecules with Multiple Stereoelements? A
      Case Study of Vancomycin and Cognates We would like to thank Professor Dieter
      Hellwinkel for pointing out to us the stereochemical discrepancies in our review6
      and elsewhere in the literature, and Kurt Mislow for stimulating and useful
      discussions. 

PMID- 11241597
TI  - Dendralenes: The Breakthrough.

PMID- 11241598
TI  - The First Cadmium-Specific Enzyme.

PMID- 11241599
TI  - Synthesis and Structure of a Ga(84)R(20)(4-) Cluster-A Link between Metalloid
      Clusters and Fullerenes? This work, which had originally been submitted to Nature
      in September 1999 and has been presented in part in lectures since January 2000,
      was supported by the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen
      Industrie. 

PMID- 11241600
TI  - [{Rh]

PMID- 11241601
TI  - Structure and Dynamics of the Host-Guest Complex of a Molecular Tweezer: Coupling
      Synthesis, Solid-State NMR, and Quantum-Chemical Calculations S.P.B. thanks the
      Alexander von Humboldt Foundation for a research fellowship. C.O. acknowledges
      financial support by a Liebig "Habilitation" fellowship from the Fonds der
      Chemischen Industrie (FCI). This work was supported by the Deutsche
      Forschungsgemeinschaft (SFB 452) and the FCI. We thank Dr. Ingo Schnell for his
      involvement in the early part of this project, Dr. Kay Saalwachter for advice
      concerning the heteronuclear experiment, and Dr. Ulrich Burkert for his help
      during the synthesis of the complex. 

PMID- 11241602
TI  - Subtleties with Sulfur: Calixarenes as Uranophiles This work was partly supported
      by the Australian Research Council. 

PMID- 11241603
TI  - Isolation of a Highly Persistent Diphosphanyl Radical: The Phosphorus Analogue of
      a Hydrazyl This work was supported by the ETH Zurich and Swiss National Science
      Foundation. 

PMID- 11241604
TI  - Synthesis of Amino

PMID- 11241605
TI  - Active-Site Structure and Dynamics of Cytochrome c Immobilized on Self-Assembled
      Monolayers-A Time-Resolved Surface Enhanced Resonance Raman Spectroscopic Study
      This work was supported by the Deutsche Forschungsgemeinschaft, the
      Volkswagenstiftung, and the Alexander-von-Humboldt Foundation. 

PMID- 11241606
TI  - Combinatorial Libraries of Metal-Ligand Assemblies with an Encapsulated Guest
      Molecule Coordination Number Incommensurate Cluster Formation, Part 17. Financial
      support of this work was provided by NSF CHE-9709621 and a NATO-NSF exchange
      grant SRG 951516. We thank the Miller Foundation for a fellowship to M.Z. Part
      16: R. M. Yeh, M. Ziegler, D. W. Johnson, A. J. Terpin, K. N. Raymond, Inorg.
      Chem. 2001, in press. 

PMID- 11241607
TI  - Shape Selectivity in Hydrocarbon Conversion These investigations were supported
      in part by the Netherlands Research Council for Chemical Sciences (CW) with
      financial aid from the Netherlands Technology Foundation and by the Netherlands
      Organization for Scientific Research (NWO) through PIONIER. We would like to
      thank Christa Roemkens, Rob van Veen, Henk Schenk, Daan Frenkel, David Dubbeldam,
      and Marcello Rigutto for their comments on our manuscript. 

PMID- 11241608
TI  - A New, Efficient Route to Titanium-Silsesquioxane Epoxidation Catalysts Developed
      by Using High-Speed Experimentation Techniques P.P.P. is grateful for a
      studentship from TUD. 

PMID- 11241609
TI  - Design and Synthesis of Foldamers Based on an Anthracene Diels-Alder Adduct We
      thank Professor Samuel H. Gellman (University of Wisconsin) and Professors
      William F. DeGrado and Stanley J. Opella (University of Pennsylvania) for
      valuable discussions. We also thank Ms. Lori Krim and Mr. Daniel Macks for their
      experimental and computational contributions to the early stages of this work.
      Generous financial support from Boehringer-Ingelheim and Alfred P. Bader (J.K.:
      Alfred E. Bader Fellow, 1996-1998) is gratefully acknowledged. 

PMID- 11241610
TI  - Novel Pseudorotaxane-Terminated Dendrimers: Supramolecular Modification of
      Dendrimer Periphery We gratefully acknowledge the Korean Ministry of Science and
      Technology (Creative Research Initiative Program) for support of this work, and
      Professor P. K. Bharadwaj for reading the manuscript. 

PMID- 11241612
TI  - Tetranuclear Copper(I)-Biphenanthroline Gridwork: Violation of the Principle of
      Maximal Donor Coordination Caused by Intercalation and CH-to-N Forces This work
      was supported by the US National Science Foundation (CHE-9904275). We thank
      Professor Tammy Dwyer for assistance with the 2D NMR experiments. 

PMID- 11241611
TI  - Trinuclear Copper(I)-bipyridine Triskelion: Template/Bascule Control of
      Coordination Complex Stereochemistry in a Trefoil Knot Precursor This work was
      supported by the US National Science Foundation (CHE-9904275). 

PMID- 11241613
TI  - Synthesis and Fluorescence Properties of Manisyl-Substituted Terpyridine,
      Bipyridine, and Phenanthroline Manisyl=4-methoxy-2,6-dimethylphenyl. This work
      was supported by the US National Science Foundation (CHE-9904275). 

PMID- 11241614
TI  - Parallel Reactions for Enantiomeric Quantification of Peptides by Mass
      Spectrometry This work was supported by the U.S. Department of Energy, Office of
      Energy Research. W.A.T. acknowledges fellowship support from Triangle
      Pharmaceuticals. 

PMID- 11241615
TI  - Total Synthesis of Hybocarpone We thank Dr. D. H. Huang, Dr. G. Siuzdak and Dr.
      I. Ioannou for NMR spectroscopic, mass spectrometric and computational
      assistance, respectively. Financial support for this work was provided by the
      Skaggs Institute for Chemical Biology, the National Institutes of Health (USA),
      and grants from Abbott, Amgen, ArrayBiopharma, Boehringer-Ingelheim, Glaxo,
      Hoffmann-La Roche, DuPont, Merck, Novartis, Pfizer, CaPCURE, and Schering Plough.

PMID- 11241616
TI  - The First Example of Activation of Molecular Oxygen by Nickel in Ni-Al
      Hydrotalcite: A Novel Protocol for the Selective Oxidation of Alcohols Ch.V.R.
      thanks the Council of Scientific and Industrial Research (CSIR), India, for the
      award of a Senior Research Fellowship. We also thank Dr. K. V. R. Chary for
      providing TPR results of the catalysts. IICT Communication No. 4452. 

PMID- 11241617
TI  - Highly Reactive Sm(II) Macrocyclic Clusters: Precursors to N(2) Reduction This
      work was supported by the Natural Sciences and Engineering Council of Canada
      (NSERC). We are deeply indebted to Mr. M. P. Lalonde for helpful discussions and
      proofreading. 

PMID- 11241618
TI  - Enantioselective Desymmetrization of meso-Decalin Diallylic Alcohols by a New Zr
      Based Sharpless AE Process: A Novel Approach to the Asymmetric Synthesis of
      Polyhydroxylated Celastraceae Sesquiterpene Cores AE=Asymmetric epoxidation.
      Grateful acknowledgement is made to the EPSRC for a QUOTA studentship (S.J.W.)
      and to Pfizer (Drs. Alan R. Brown and John P. Mathias) for financial support of
      this work. 

PMID- 11241619
TI  - The First Crystalline Calcium Porphyrin and Tetrakis(tert
      butylphenyl)porphyrinato Calcium(II): Its Synthesis, Structure, and Binding
      Properties Towards Alkali and Alkaline Earth Metal Salts This work was supported
      by the Fonds National Suisse de la Recherche Scientifique (Grant No. 20-53336.98)
      and Action COST D9 (European Programme for Scientific Research, OFES No.
      C98.008). 

PMID- 11241620
TI  - [W]

PMID- 11241621
TI  - Origin and True Nature of the Starter Unit for the Rapamycin Polyketide Synthase
      We thank Dr. Bradley S. Moore for help with the deuterium NMR experiments. This
      work was supported by grants from The Wellcome Trust (to J.S. and P.F.L.) and
      from the NIH (AI20264 to H.G.F.). 

PMID- 11241622
TI  - A Novel Approach for the One-Pot Preparation of alpha-Amino Amides by Pd
      Catalyzed Double Carbohydroamination We are grateful to the Natural Sciences and
      Engineering Research Council of Canada for support of this research. 

PMID- 11241623
TI  - A Neutral Three-Coordinate Alkylrhodium(I) Complex: Stabilization of a 14
      Electron Species by gamma-C-H Agostic Interactions with a Saturated Hydrocarbon
      Group This work was supported by the Deutsche Forschungsgemeinschaft (SFB 247,
      Graduate College Fellowship to H.U.), by the BASF AG, by the Degussa-Huls AG, by
      the Fonds der Chemischen Industrie, and by the EU. 

PMID- 11241624
TI  - YBa(2)Cu(3)O(6+delta) as an Oxygen Separation Membrane This work was supported by
      the National Natural Science Foundation of China and the National Advanced
      Materials Committee of China. 

PMID- 11241625
TI  - C(60)F(20): "Saturnene", an Extraordinary Squashed Fullerene This work was
      supported by a Joint Project Grant from the Royal Society, INTAS (grant no. 97
      30027), NATO, and the Russian Programme, "Fullerene and Atomic Clusters". We
      thank Prof. P. W. Fowler for very helpful discussion, and B. de La Vaissierre for
      the AM1, PM3, and MNDO calculations. 

PMID- 11241626
TI  - Geminal Difunctionalization of Alkenylidene-Type Carbenoids by Using Interelement
      Compounds.

PMID- 11241627
TI  - Nitroxide Radicals as Templating Agents in the Synthesis of Magnets Based on
      Three-Dimensional Oxalato-Bridged Heterodimetallic Networks This work was
      supported by the European Union (TMR ERB 4061 PL97-0197) and the Ministerio de
      Ciencia y Tecnologia (MCT) (Project no. MAT98-0880). C.G. and F.M.R. wish to
      thank the MCT for a research contract (Contrato de Reincorporacion). 

PMID- 11241628
TI  - Synthesis and Characterization of

PMID- 11241630
TI  - The Type 2 Intramolecular Diels-Alder Reaction: Synthesis and Chemistry of
      Bridgehead Alkenes.
AB  - Anti-Bredt alkenes, bicyclic molecules that contain a bridgehead double bond,
      were for many years regarded as chemical curiosities. The type 2 intramolecular
      Diels-Alder (IMDA) reaction provides a one-step entry into this fascinating class
      of molecules. The reaction has made available numerous anti-Bredt alkenes for
      structural and chemical studies. X-ray crystallography has revealed the magnitude
      of the deformations associated with the bridgehead double bond, and rate studies
      of reactions of bridgehead alkenes have allowed quantification of the kinetic
      consequences of the torsional distortions. More recently, the type 2
      intramolecular Diels-Alder reaction and the resulting anti-Bredt alkenes have
      found application in organic synthesis. The constraints resulting from the
      connectivity in the Diels-Alder precursor creates a strong regio- and
      stereochemical bias in the cycloaddition step. The end result of this bias is the
      stereoselective synthesis of highly substituted six-membered rings. The reaction
      also achieves a facile synthesis of seven- and eight-membered rings in a single
      step from acyclic precursors. The utility of this reaction has been verified in
      recent applications of the type 2 IMDA reaction as a key step in the total
      synthesis of complex natural products.

PMID- 11241631
TI  - Fronts, Waves, and Stationary Patterns in Electrochemical Systems In the appendix
      we list the minimal equations (prototype equations) that describe the phenomena
      of self-organization discussed in the individual sections. 
AB  - Oscillatory behavior has been observed for almost all electrochemical reactions
      in a certain, although sometimes small, range of external parameters. Only in the
      past ten years has it been possible, however, to find a common explanation for
      the occurrence of these temporal self-organization phenomena of chemically
      completely different electrochemical reactions. The breakthrough was achieved
      because new methods and concepts, which had been developed in nonlinear dynamics
      to describe the spontaneous formation of order in various disciplines, could be
      applied. This development in turn was only possible because the underlying laws
      are universal at a certain abstract level. Oscillations are only one possible
      manifestation of nonlinear behavior. Examples of other features that are often
      closely associated with temporal instabilities are spatial structures and waves.
      Initiated by the theoretical progress and the development of new experimental
      techniques, spatial pattern formation in electrochemical systems has been
      targeted for investigations in the past few years. Based on these investigations,
      it can be predicted under which conditions temporal or spatial pattern formation
      can be expected. Furthermore, the possibility of predicting the occurrence of
      instabilities indicates that it might be feasible to exploit nonlinear effects to
      increase, for example, the yield of electrocatalytic reactions. Here we discuss
      physicochemical mechanisms that lead to pattern formation in electrochemical
      systems. At the same time, we stress the generic principles that are responsible
      for self-structuring processes in many chemical and biological systems.

PMID- 11241632
TI  - In Vivo Protein-Protein Interaction Assays: Beyond Proteins We would like to
      thank Tony Siu, Dr. Charles Cho, and the members of our lab for their helpful
      comments as we were preparing this manuscript. 

PMID- 11241633
TI  - Recent Developments in Catalytic Asymmetric Strecker-Type Reactions.

PMID- 11241634
TI  - Intramolecular DNA Coiling Mediated by a Metallo-Supramolecular Cylinder Support
      by the Leverhulme Trust (F/215/BC) and the EPSRC lifesciences interface network
      (GR/M91105) is gratefully acknowledged. Discussions with Julie MacPherson have
      been of great assistance during preparation of the manuscript. 

PMID- 11241635
TI  - Unique Single-Atom Binding of Pseudohalogeno Ligands to Four Metal Ions Induced
      by Their Trapping into High-Nuclearity Cages This work was supported by CICYT
      (Grant BP96/0163) and the Research Committee of the University of Patras (C.
      Caratheodory Programme, No 1941). 

PMID- 11241636
TI  - Evidence for the Existence of the McMillan Phase in a Binary System of a
      Metallomesogen and 2,4,7-Trinitrofluorenone This work was supported by the
      Deutsche Forschungsgemeinschaft. 

PMID- 11241637
TI  - Multilayer Formation on a Curved Drop Surface This work was supported by the Max
      Planck-Gesellschaft, the President fund of the Chinese Academy Science as well as
      the National Natural Science Foundation of China (NNSFC). We thank Marc Schneider
      for performing the atomic force mircoscopy (AFM) measurements and H. Mohwald
      (MPI, Golm) for critically reading the manuscript. 

PMID- 11241638
TI  - Chiral Molecular Recognition on Formation of a Metalloanthocyanin: A
      Supramolecular Metal Complex Pigment from Blue Flowers of Salvia patens We thank
      Mr. Y. Maeda (Chemical Instrument Center, Nagoya University) for help with
      molecular modeling, and the Ministry of Education, Science, Sports, and Culture
      of Japan (COE Research No. 07CE2004) for financial support. 

PMID- 11241639
TI  - Synthesis of an Array Comprising 837 Variants of the hYAP WW Protein Domain This
      work was supported by the DFG (INK 16/B1-1), by the Fonds der Chemischen
      Industrie, and by the Universitatsklinikum Charite Berlin. 

PMID- 11241640
TI  - Total Synthesis of the Macrolide Antibiotic 5,6-Dihydrocineromycin B This work
      was supported by the DFG (SFB 416) and the Fonds der Chemischen Industrie. We
      thank Prof. Dr. A. Zeeck for supplying data of the title compound, as well as
      BASF, Degussa-Huls and Wacker-Chemie for donations of chemicals. 

PMID- 11241641
TI  - A Novel Concept in Combinatorial Chemistry in Solution with the Advantages of
      Solid-Phase Synthesis: Formation of N-Betaines by Multicomponent Domino Reactions
      This work was supported as part of the BMBF Project "Kombinatorische Chemie"
      (grant number 03 D0056 2). We thank BASF AG, Ludwigshafen, and the Fonds der
      Chemischen Industrie for generous support. 

PMID- 11241642
TI  - Spatially Resolved Detection of Neurotransmitter Secretion from Individual Cells
      by Means of Scanning Electrochemical Microscopy.

PMID- 11241643
TI  - "Supramolecular" Solid-State Chemistry: Interpenetrating Diamond-Type Frameworks
      of U(4+) Ions Linked by S,S'-Bidentate P(2)S(6)(2-) Molecular Rods in UP(4)S(12)
      This work was supported by the Deutsche Forschungsgemeinschaft. 

PMID- 11241644
TI  - sigma-Bishomoconjugation (sigma-Bishomoaromaticity) in 4C/3(2)e Cations-Scope and
      Limitations This project has been supported by the Deutsche
      Forschungsgemeinschaft, the Fonds der Chemischen Industrie, and BASF AG. We thank
      A. Kurscheidt and M. Lutterbeck for technical assistance, Dr. D. Hunkler and Dr.
      J. Worth for NMR and MS measurements, and Prof. Dr. T. Bally for access to his
      (60)Co-gamma-irradiation equipment. 

PMID- 11241645
TI  - A Versatile and High-Yield Route to Active and Well-Defined Catalysts

PMID- 11241646
TI  - A New Photomagnetic Molecular System Based on Photoinduced Self-Assembly of
      Radicals This work was supported by grants from DGI (project MAT 2000-1388-C03
      01), CIRIT (project 2000 SGR00114), the 3MD Network of the TMR program of the EU
      (contract ERBFMRX CT980181), and the ESF program Molecular Magnets. D.R.-M.
      thanks the Generalitat de Catalunya for a postdoctoral grant, and I.R. thanks the
      CSIC-Carburos Metalicos and ESF for fellowships. 

PMID- 11241647
TI  - Fluoroprolines as Tools for Protein Design and Engineering We thank Mrs. E.
      Weyher for skillful technical assistance in spectroscopic analyses and Mrs. W.
      Wenger for her excellent technical assistance in protein preparation. We are
      indebted to Dr. R. Golbik for providing us with barstar plasmid and protocols for
      its isolation and purification. 

PMID- 11241648
TI  - Highly Enantioselective Copper-Phosphoramidite Catalyzed Kinetic Resolution of
      Chiral 2-Cyclohexenones This work was supported by the Dutch Foundation for
      Scientific Research (NWO). 

PMID- 11241649
TI  - Highly Enantioselective Regiodivergent and Catalytic Parallel Kinetic Resolution
      This work was supported by the Ministero dell'Universita e della Ricerca
      Scientifica e Tecnologica (MURST, Roma) and by the University of Pisa. We
      gratefully acknowledge Merck for the generous financial support derived from the
      2000 ADP Chemistry Award. 

PMID- 11241650
TI  - From Oligomers to Conducting Polymers of the Metal-Dinitrogen Functionality This
      work was supported by the "Fonds National Suisse de la Recherche Scientifique"
      (Grant No. 20-53336.98), Action COST D9 (European Program for Scientific
      Research, OFES No. C98.008), and Fondation Herbette (University of Lausanne). 

PMID- 11241651
TI  - Hydrogen Bond in Molecules with Large-Amplitude Motions: A Rotational Study of
      Trimethylene Sulfide small middle dot small middle dot small middle dotHCl The
      authors would like to thank the Direccion General de Ensenanza Superior (DGES
      Grant PB96-0366) and the Junta de Castilla y Leon (JCL Grants VA51/96 and
      VA04/98) for support of this work. M.E.S. gratefully acknowledges an FPI grant
      from the Ministerio de Educacion y Cultura. 

PMID- 11241652
TI  - Revolutionizing Resin Handling for Combinatorial Synthesis.

PMID- 11241653
TI  - Adsorption-Mediated Electrochemical Sensing of Halides We gratefully acknowledge
      financial support from the Office of Naval Research through their Young
      Investigator Program. We thank D. Kong for various helpful discussions and the
      Austrian Science Fund for an Erwin Schrodinger Fellowship to R.M. 

PMID- 11241654
TI  - Mid-Membrane Photolabeling of the Transmembrane Domain of Glycophorin A in
      Phospholipid Vesicles This work was supported in part by the Japan Science and
      Technology Corporation (JST), the Universite Louis Pasteur (ULP) "Supermolecules"
      Joint Research Project, and the European Union (DG-XII, contract PL 950990). We
      are grateful for support granted by JST to N.H., by the Herrmann-Schlosser
      Stiftung and the Stiftung zur Forderung Korperbehinderter to W.H., and by the
      "Societe des Amis des Sciences" of France to P.G. We also thank Dr. F. Pattus,
      Dr. G. Cremel, Dr. P. Hubert, Dr. A. Van Dorsselaer (Strasbourg), Dr. J. L.
      Rigaud, and Dr. J. L. Popot (Paris) for stimulating discussions. 

PMID- 11241655
TI  - A Direct and Efficient alpha-Selective Glycosylation Protocol for the Kedarcidin
      Sugar, L-Mycarose: AgPF(6) as a Remarkable Activator of 2-Deoxythioglycosides
      This work was supported by CREST, and fellowships (to M.J.L. and F.Y.) from the
      Japanese Society for the Promotion of Science are gratefully acknowledged. 

PMID- 11241656
TI  - H(2)O(2)-Dependent Fe-Catalyzed Oxidations: Control of the Active Species We
      thank the EU for financial support (TMR program (ERBMRFXCT980207). 

PMID- 11241657
TI  - A Route to a Germanium-Carbon Triple Bond: First Chemical Evidence for a Germyne
      We thank Prof. Dr. Josef Michl (University of Colorado at Boulder, USA) for
      helpful discussions. 

PMID- 11241658
TI  - Heterogeneous Dinuclear Rhodium(II) Hydroformylation Catalysts-Performance
      Evaluation and Silsesquioxane-Based Chemical Modeling M.N. gratefully
      acknowledges two successive Senior Research Fellowships from Universitat de
      Valencia and T.U. Delft and support from the TMR Network. 

PMID- 11241659
TI  - Ruthenium-Catalyzed Regioselective alpha-Alkylation of Ketones: The First Alkyl
      Group Transfer from Trialkylamines to the alpha-C Atom of Ketones This work was
      supported by the Basic Research Program of the Korea Science and Engineering
      Foundation (2000-2-12200-001-3). C.S.C. gratefully acknowledges a Post-Doctoral
      Fellowship of Kyungpook National University (2000). 

PMID- 11241660
TI  - Half-Metallocene Tantalum Complexes Bearing Methyl Methacrylate (MMA) and 1,4
      Diaza-1,3-diene Ligands as MMA Polymerization Catalysts We thank Professor
      emeritus A. Nakamura (Osaka University) for fruitful discussions. The present
      research was supported in part by a grant-in-aid for Scientific Research on
      Priority Areas "Molecular Physical Chemistry" from the Ministry of Education,
      Science, Culture, and Sports. Y.M. is a research fellow of the Japan Society for
      the Promotion of Science, 1998-2000. 

PMID- 11241661
TI  - The rate of folate receptor alpha (FR alpha) synthesis in folate depleted CHL
      cells is regulated by a translational mechanism sensitive to media folate levels,
      while stable overexpression of its mRNA is mediated by gene amplification and an
      increase in transcript half-life.
AB  - DC-3F/FA3 cells (FA3) were obtained by selection of Chinese hamster lung
      fibroblasts for growth in folic acid free media, supplemented with 15 pM [6S]-5
      formyltetrahydrofolic acid. These cells, as a result of low level gene
      amplification and RNA stabilization, were found to overexpress folate receptor
      alpha (FR alpha) mRNA by more than five hundred fold. The expression level of the
      receptor, a 43 kDa GPI-linked plasma membrane glycoprotein, was found to be
      inversely related to changes in media folate concentrations while its steady
      state mRNA level remained unaffected. In low folate, the rate of receptor
      synthesis was found to increase by more than three fold, while its half-life
      stabilized as compared to that observed in high folate media. Although DC-3F
      cells were found to contain low amounts of FR alpha mRNA, receptor expression was
      undetectable, and changing media folate concentrations had no effect on the
      expression of either. Hence, while selection for growth in low folate leads to
      stable overexpression of FR alpha mRNA, receptor expression is regulated at the
      level of protein synthesis by a mechanism sensitive to media folate levels.

PMID- 11241662
TI  - Dynamics of extracellular matrix production and turnover in tissue engineered
      cardiovascular structures.
AB  - Appropriate matrix formation, turnover and remodeling in tissue-engineered small
      diameter vascular conduits are crucial requirements for their long-term patency
      and function. This complex process requires the deposition and accumulation of
      extracellular matrix molecules as well as the remodeling of this extracellular
      matrix (ECM) by matrix metalloproteinases (MMPs) and their endogenous inhibitors
      (TIMPs). In this study, we have investigated the dynamics of ECM production and
      the activity of MMPs and TIMPs in long-term tissue-engineered vascular conduits
      using quantitative ECM analysis, substrate gel electrophoresis, radiometric
      enzyme assays and Western blot analyses. Over a time period of 169 days in vivo,
      levels of elastin and proteoglycans/glycosaminoglycans in tissue-engineered
      constructs came to approximate those of their native tissue counter parts. The
      kinetics of collagen deposition and remodeling, however, apparently require a
      much longer time period. Through the use of substrate gel electrophoresis,
      proteolytic bands whose molecular weight was consistent with their identification
      as the active form of MMP-2 (approximately 64--66 kDa) were detected in all
      native and tissue-engineered samples. Additional proteolytic bands migrating at
      approximately 72 kDa representing the latent form of MMP-2 were detected in
      tissue-engineered samples at time points from 5 throughout 55 days. Radiometric
      assays of MMP-1 activity demonstrated no significant differences between the
      native and tissue-engineered samples. This study determines the dynamics of ECM
      production and turnover in a long-term tissue-engineered vascular tissue and
      highlights the importance of ECM remodeling in the development of successful
      tissue-engineered vascular structures.

PMID- 11241663
TI  - Insulin-like growth factor binding proteins in femoral and vertebral bone marrow
      stromal cells: expression and regulation by thyroid hormone and dexamethasone.
AB  - Insulin-like growth factor (IGF)-I is an important regulator of bone metabolism.
      Clinical observations suggest that different anatomic sites within the adult
      skeleton respond differently to hormonal and therapeutic treatment, and recent
      studies on bone marrow stromal cells in culture show that there are skeletal site
      dependent differences in the gene expression of IGF-I. The actions of IGF-I and 
      II on bone cells are known to be modulated by the IGF binding proteins (IGFBP)-1
      through -6 and the Type I and Type II IGF receptors. Therefore, we compared the
      expression of IGFBP-1 through -6 in adult female rat bone marrow stromal cell
      cultures derived from two separate skeletal sites: vertebrae and femurs. The
      cultures were maintained simultaneously under conditions that support osteoblast
      differentiation from osteoprogenitors present in the femoral and vertebral marrow
      cell populations. We also addressed whether IGFBP messenger RNA levels are
      regulated by thyroid hormone (T(3)) and dexamethasone (dex) treatment in femoral
      vs. vertebral marrow stromal cells in vitro, since steroid hormones play an
      important role in skeletal function. Northern blot analyses revealed that there
      are distinct skeletal site differences in the gene expression of IGFBPs. The
      vertebral marrow cultures express IGFBP-2 through -6 mRNAs, with IGFBP-2, IGFBP
      4, and IGFBP-6 mRNAs predominating. The femoral marrow stromal cell cultures
      express only IGFBP-4 and IGFBP-6. Importantly, vertebral marrow cultures have
      much higher IGFBP mRNA steady-state levels than femoral cultures for all the
      detected IGFBP transcripts. IGFBP-1 is not detected in either femoral or
      vertebral cultures. In addition to a skeletal site difference, we show that T(3)
      and dex regulate the expression of specific IGFBP mRNAs. T(3) treatment also
      upregulates IGF-I protein secretion by vertebral marrow stromal cell cultures.
      Interestingly, the type I receptor for IGF-I was expressed equivalently in
      cultures from the two skeletal sites. These findings have important implications
      for the anatomical site specificities of hormonal responses that are noted in the
      skeleton.

PMID- 11241664
TI  - Gastric cancer cell lines as models to study human digestive functions.
AB  - The present investigation aims at defining the functional status of several
      gastric cancer cell lines in order to assess their usefulness as adequate
      cellular models to study the regulation of gastric digestive functions. Compared
      to AGS, Hs746t and KATO-III cells, NCI-N87 exhibited an unique differentiation
      status. They formed coherent monolayers expressing E-cadherin and ZO-1 junctional
      proteins; their integrity and epithelial morphology were maintained at post
      confluency for up to 10 days. All cell lines synthesized PAS-reactive (mucous
      type) glycoconjugates. However, only NCI-N87 cells expressed MUC6 glycoprotein
      suggesting a mucopeptic phenotype. Immunostaining, enzymatic assays, Western
      blotting and Reverse Transcriptase polymerase chain reaction (RT-PCR) revealed
      that all cell lines contained varying levels of pepsinogen (Pg5) and human
      gastric lipase (HGL). Only NCI-N87 cells were able to express zymogens at higher
      levels, in granule-like structures, and to efficiently secrete both HGL and Pg5.
      The addition of epidermal growth factor (EGF) to post-confluent NCI-N87 cells,
      which exhibit an abundant membrane staining for EGF-receptors, modulated HGL
      activity without affecting Pg5. In conclusion, this investigation enlightens the
      potential usefulness of the gastric cell line NCI-N87 as a model for elucidating
      the cellular and molecular mechanisms involved in the regulation of human gastric
      epithelial functions.

PMID- 11241665
TI  - Sucrase-alpha-dextrinase in the spontaneously diabetic BioBreed Wistar rat:
      altered intracellular carbohydrate processing.
AB  - Sucrase-alpha-dextrinase (S-D), a glycoprotein hydrolase in the border surface of
      the enterocyte, is altered in congenitally diabetic BioBreed Wistar (BB(d)) rats.
      Its intracellular assembly was examined in the current studies. Following pulse
      chase experiments, S--D was specifically immuno-isolated from ER-Golgi and brush
      border membranes, and examined by SDS-PAGE and autoradiography. While synthesis
      and co-translational glycosylation of an immature species, P(i), in the ER
      proceeded normally, post-translational maturation of the N-linked carbohydrate
      chains was altered in the BB(d) rat. The mature species, P(m), was 10 kDa larger
      in BB(d) than in normal rats, and approximately 25% of its N-linked chains
      remained immature. The difference in mass was attributed to an appreciably larger
      mass of the O-linked chains of P(m) in BB(d) rats. In vivo kinetics of
      intracellular assembly displayed a delay in the appearance of P(m) in Golgi
      (Wistar, 15 min; BB(d), 30--60 min). These experiments, revealing structural
      alterations in congenital diabetes suggest an important role for intracellular
      glycosylation in the orderly assembly and processing of brush border S-D in the
      enterocyte.

PMID- 11241666
TI  - Upstream stimulating factor-1 (USF1) and USF2 bind to and activate the promoter
      of the adenomatous polyposis coli (APC) tumor suppressor gene.
AB  - The adenomatous polyposis coli (APC) gene product is involved in cell cycle
      arrest and apoptosis, and loss of function is associated with the development of
      colorectal carcinogenesis. Although it has been demonstrated that the APC gene is
      inducible, its transcriptional regulation has not been elucidated. Therefore, we
      characterized the promoter region of the APC gene and transcription factors
      required for basal expression. The APC gene has a TATA-less promoter and contains
      consensus binding sites for Octamer, AP2, Sp1, a CAAT-box, and three nucleotide
      sequences for E-box A, B, and M. The E-boxes are functional in several cancer
      cell lines and upstream stimulating factor-1 (USF1) and USF2 interact with these
      sites, with a preferred sequence-specificity for the B site. Analysis of
      activation of the cloned APC promoter by USF1 and USF2 in transient transfection
      assays in HCT-116 cells demonstrated that mutation of the E-box B site completely
      abolished the basal promoter activity. Further, the ectopic USF1 and USF2
      expression in HCT-116 cells with deletion mutations of E-box A, B, and M sites
      showed that these E-boxes contribute to USF1- and USF2-mediated transcriptional
      activation of the APC promoter, with maximum promoter activity being associated
      with the E-box B site. Thus, USF1 and USF2 transcription factors are critical for
      APC gene expression.

PMID- 11241667
TI  - Electromagnetic acceleration of electron transfer reactions.
AB  - The Moving Charge Interaction (MCI) model proposes that low frequency
      electromagnetic (EM) fields affect biochemical reactions through interaction with
      moving electrons. Thus, EM field activation of genes, and the synthesis of stress
      proteins, are initiated through EM field interaction with moving electrons in
      DNA. This idea is supported by studies showing that EM fields increase electron
      transfer rates in cytochrome oxidase. Also, in studies of the Na,K-ATPase
      reaction, estimates of the speed of the charges accelerated by EM fields suggest
      that they too are electrons. To demonstrate EM field effects on electron transfer
      in a simpler system, we have studied the classic oscillating Belousov-
      Zhabotinski (BZ) reaction. Under conditions where the BZ reaction oscillates at
      about 0.03 cycles/sec, a 60 Hz, 28 microT (280 mG) field accelerates the overall
      reaction. As observed in earlier studies, an increase in temperature accelerates
      the reaction and decreases the effect of EM fields on electron transfer. In all
      three reactions studied, EM fields accelerate electron transfer, and appear to
      compete with the intrinsic chemical forces driving the reactions. The MCI model
      provides a reasonable explanation of these observations.

PMID- 11241669
TI  - Inhibition effects of di(2-ethylhexyl)phthalate on mouse-liver lysosomal vacuolar
      H(+)-ATPase.
AB  - We investigated the effects of di(2-ethylhexyl)phthalate (DEHP) on mouse-liver
      lysosomes. After 2 weeks of oral administration in mice, a reduction in vacuolar
      H(+)-ATPase (V-ATPase) was observed, and after 3 weeks, the liver lysosomal
      compartment was completely negative for V-ATPase, as determined by
      immunocytochemical analysis. When the mice were subsequently fed a normal diet
      for 1 week, V-ATPase levels recovered to normal values. According to Northern
      blot analysis, V-ATPase subunit A mRNA decreased gradually with DEHP treatment.
      Enzyme cytochemical staining showed acid phosphatase (AcPase) to be present in
      lysosomes and late autophagosomes (autolysosomes) in normal animals as well as in
      DEHP-treated animals. But the number of late autophagosomes containing AcPase
      increased clearly after DEHP treatment. These results suggest that: (1) DEHP
      causes marked V-ATPase reduction in the liver lysosomal compartment and the
      effect of DEHP is reversible; and (2) the effect of DEHP on protein expression is
      likely to be exerted at the transcriptional level.

PMID- 11241668
TI  - BMP-2 induction and TGF-beta 1 modulation of rat periosteal cell chondrogenesis.
AB  - Periosteum contains osteochondral progenitor cells that can differentiate into
      osteoblasts and chondrocytes during normal bone growth and fracture healing. TGF
      beta 1 and BMP-2 have been implicated in the regulation of the chondrogenic
      differentiation of these cells, but their roles are not fully defined. This study
      was undertaken to investigate the chondrogenic effects of TGF-beta 1 and BMP-2 on
      rat periosteum-derived cells during in vitro chondrogenesis in a three
      dimensional aggregate culture. RT-PCR analyses for gene expression of cartilage
      specific matrix proteins revealed that treatment with BMP-2 alone and combined
      treatment with TGF-beta 1 and BMP-2 induced time-dependent mRNA expression of
      aggrecan core protein and type II collagen. At later times in culture, the
      aggregates treated with BMP-2 exhibited expression of type X collagen and
      osteocalcin mRNA, which are markers of chondrocyte hypertrophy. Aggregates
      incubated with both TGF-beta 1 and BMP-2 showed no such expression. Treatment
      with TGF-beta 1 alone did not lead to the expression of type II or X collagen
      mRNA, indicating that this factor itself did not independently induce
      chondrogenesis in rat periosteal cells. These data were consistent with
      histological and immunohistochemical results. After 14 days in culture, BMP-2
      treated aggregates consisted of many hypertrophic chondrocytes within a
      metachromatic matrix, which was immunoreactive with anti-type II and type X
      collagen antibodies. In contrast, at 14 days, TGF-beta 1 + BMP-2-treated
      aggregates did not contain any morphologically identifiable hypertrophic
      chondrocytes and their abundant extracellular matrix was not immunoreactive to
      the anti-type X collagen antibody. Expression of BMPR-IA, TGF-beta RI, and TGF
      beta RII receptors was detected at all times in each culture condition,
      indicating that the distinct responses of aggregates to BMP-2, TGF-beta 1 and TGF
      beta 1 + BMP-2 were not due to overt differences in receptor expression.
      Collectively, our results suggest that BMP-2 induces neochondrogenesis of rat
      periosteum-derived cells, and that TGF-beta 1 modulates the terminal
      differentiation in BMP-2 induced chondrogenesis.

PMID- 11241670
TI  - The cell survival signal Akt is differentially activated by PDGF-BB, EGF, and FGF
      2 in osteoblastic cells.
AB  - Stimulation of osteoblast survival signals may be an important mechanism of
      regulating bone anabolism. Protein kinase B (PKB/Akt), a serine-threonine protein
      kinase, is a critical regulator of normal cell growth, cell cycle progression,
      and cell survival. In this study we have investigated the signaling pathways
      activated by growth factors PDGF-BB, EGF, and FGF-2 and determined whether PDGF
      BB, EGF, and FGF-2 activated Akt in human or mouse osteoblastic cells. The
      results demonstrated that both ERK1 and ERK2 were activated by FGF-2 and PDGF-BB.
      Activation of ERK1 and ERK2 by PDGF-BB and FGF-2 was inhibited by PD 098059 (100
      microM), a specific inhibitor of MEK. Wortmannin (500 nM), a specific inhibitor
      of phosphatidylinositol 3-kinase ( PI 3-K), inhibited the activation of ERK1 and
      ERK2 by PDGF-BB but not by FGF-2 suggesting that PI 3-K mediated the activation
      of ERK MAPK pathway by PDGF-BB but not by FGF-2. Rapamycin, an inhibitor of p70
      S6 protein kinase and a downstream target of ERK1/2 and PI 3-K, did not affect
      the activation of ERK1 and ERK2 by the growth factors. Furthermore, our results
      demonstrated that Akt, a downstream target of PI 3-K, was activated by PDGF-BB
      but not by FGF-2. Akt activation by PDGF-BB was inhibited by PI 3-kinase
      inhibitor LY294002. Rapamycin had no effect on Akt activation. Epidermal growth
      factor (EGF) also activated Akt in osteoblastic cells which was inhibited by
      LY294002 but not by rapamycin. Taken together, our data for the first time
      revealed that the activation of ERK1/2 by PDGF-BB is mediated by PI 3-K, and
      secondly, Akt is activated by PDGF-BB and EGF but not by FGF-2 in human and mouse
      osteoblastic cells. These results are of critical importance in understanding the
      role of these growth factors in apoptosis and cell survival. PDGF-BB and EGF but
      not FGF-2 may stimulate osteoblast cell survival.

PMID- 11241671
TI  - Adipogenic potential of human adipose derived stromal cells from multiple donors
      is heterogeneous.
AB  - The current study was done to assess if heterogeneity existed in the degree of
      adipogenesis in stromal cells (preadipocytes) from multiple donors. In addition
      to conventional lipid-based methods, we have employed a novel signal
      amplification technology, known as branched DNA, to monitor expression of an
      adipocyte specific gene product aP2. The fatty acid binding protein aP2 increases
      during adipocyte differentiation and is induced by thiazolidinediones and other
      peroxisome proliferator activated receptor gamma ligands. The current work
      examined the adipogenic induction of aP2 mRNA levels in human adipose tissue
      stromal cells derived from 12 patients (mean age +/- SEM, 38.9 +/- 3.1) with mild
      to moderate obesity (mean body mass index +/- SEM, 27.8 +/- 2.4). Based on
      branched DNA technology, a rapid and sensitive measure of specific RNAs, the
      relative aP2 level in adipocytes increased by 679 +/- 93-fold (mean +/- SEM,
      n=12) compared to preadipocytes. Normalization of the aP2 mRNA levels to the
      housekeeping gene, glyceraldehyde phosphate dehydrogenase, did not significantly
      alter the fold induction in a subset of 4 patients (803.6 +/- 197.5 vs 1118.5 +/-
      308.1). Independent adipocyte differentiation markers were compared between
      adipocytes and preadipocytes in parallel studies. Leptin secretion increased by
      up to three-orders of magnitude while measurements of neutral lipid accumulation
      by Oil Red O and Nile Red staining increased by 8.5-fold and 8.3-fold,
      respectively. These results indicate that preadipocytes isolated from multiple
      donors displayed varying degrees of differentiation in response to an optimal
      adipogenic stimulus in vitro. This work also demonstrates that branched DNA
      measurement of aP2 is a rapid and sensitive measure of adipogenesis in human
      stromal cells. The linear range of this assay extends up to three-orders of
      magnitude and correlates directly with independent measures of cellular
      differentiation.

PMID- 11241672
TI  - Cloning and characterization of the murine beta(3) integrin gene promoter:
      identification of an interleukin-4 responsive element and regulation by STAT-6.
AB  - Expression of the alpha(v)beta(3) integrin by murine bone marrow macrophages is
      regulated by cytokines such as IL-4 and GM-CSF through transcriptional activation
      of the beta(3) subunit gene. To characterize the molecular mechanisms by which
      such regulation occurs, we isolated the murine beta(3) integrin promoter. To this
      end, we first cloned a full length beta(3) cDNA and used the 5'UTR and leader
      peptide coding sequence to identify genomic clones containing the beta(3)
      promoter region. The transcriptional start site, identified by primer extension
      and S1 nuclease assay, is 34 nt upstream of the translation initiation codon. A
      1.1 kb fragment of the promoter region drives IL-4 responsive transcription in
      transiently transfected murine bone marrow macrophages. Deletion analysis of the
      beta(3) promoter indicates the IL-4 responsive element lies between -465 to -678
      nt relative to the transcriptional start site. This promoter fragment contains
      two overlapping STAT consensus recognition sites and nuclear extracts from BMMs
      contain an IL-4-inducible DNA binding factor, identified by super shift analysis,
      as STAT-6. Furthermore, an oligonucleotide which includes the two STAT
      recognition sites residing in the IL-4 responsive region of the beta(3) promoter,
      competes for STAT-6 binding. Confirming IL-4 induction of the integrin subunit is
      specifically mediated by STAT-6, beta(3) mRNA is not enhanced in BMMs derived
      from STAT-6 deleted mice, which however, retain their capacity to respond to GM
      CSF.

PMID- 11241673
TI  - Characterisation of nuclear localisation signals of the four human core histones.
AB  - The four core histones H2A, H2B, H3 and H4 are transported from the cytoplasm
      into the nucleus by a receptor-mediated and energy-dependent process. This
      nuclear transport depends on topogenic signals in the individual histone protein
      sequences. We have analysed such nuclear localisation signals in the core
      histones by means of fusion proteins consisting of individual core histones (or
      fragments thereof) and beta-galactosidase as a reporter protein. The results show
      that each of the four core histones contains several portions that are capable of
      mediating nuclear transport. One type of topogenic sequences consists of
      clustered basic amino acids in the amino terminal segments of each of the core
      histones. The globular portions of the core histones represent a second type of
      nuclear localisation signals that could only mediate nuclear transport when the
      whole protein domains were fused to the beta-galactosidase reporter. Fragments of
      the globular domains derived from each of the four core histones could not serve
      as nuclear localisation signals. We conclude that the nuclear targeting of core
      histones requires information conferred by the globular domain conformation.

PMID- 11241674
TI  - Proteasome activity is required for T lymphocyte aggregation after mitogen
      activation.
AB  - The proteasome is a multicatalytic complex of proteases involved in T lymphocyte
      proliferation and activation through multiple mechanisms. In this study, we
      investigated its role in lymphocyte aggregation. We found that blocking
      proteasome activity by a proteasome-specific inhibitor lactacystin (LAC)
      prevented clustering of T lymphocytes after stimulation with various mitogens.
      Expression of adhesion molecules ICAM-1 and LFA-1 at cell surfaces of activated T
      cells was decreased after treatment with LAC. Mechanisms by which the proteasome
      intervenes in the expression of these adhesion molecules were different. LAC
      inhibited ICAM-1 expression at the mRNA level, whereas LFA-1 inhibition was
      probably at a post-translational level. Downregulation of these molecules after
      proteasome inhibition likely contributes to the observed repression of T cell
      aggregation. Our results show that the proteasome plays an important role in cell
      cell interaction during T cell activation.

PMID- 11241675
TI  - 1 alpha,25-Dihydroxyvitamin D(3) inhibits rat liver ultrastructural changes in
      diethylnitrosamine-initiated and phenobarbital promoted rat hepatocarcinogenesis.
AB  - The active metabolite of vitamin D, 1 alpha,25-dihydroxyvitamin
      D(3)[1,25(OH)(2)D(3)] has been receiving increasing attention and has come to the
      forefront of cancer chemoprevention research as being a regulator of cellular
      growth, differentiation and death. In the present study, attempts have been made
      to investigate the in vivo chemopreventive effect of 1,25(OH)(2)D(3) in two-stage
      rat liver carcinogenesis. Hepatocarcinogenesis was initiated with a single
      intraperitoneal injection of diethylnitrosamine [DEN] (200 mg/kg b. wt.) at week
      4. After a brief recovery period of 2 weeks, all the DEN-treated rats were given
      phenobarbital (0.05%) in the basal diet and continued thereafter till the
      completion of the experiment. The results of our experiment showed that the rats
      which received 1,25(OH)(2)D(3) for 14 weeks (0.3 microg/100 microL propylene
      glycol, per os, twice a week), starting the treatment 4 weeks prior to DEN
      injection, exhibited maximum protective effect in maintaining the normal cellular
      architecture of the hepatocytes than the group of rats which received this
      micronutrient for only 9 weeks. Moreover, continuous supplementation of
      1,25(OH)(2)D(3) maintains the concentration of hepatic microsomal cytochrome P
      450 like that of normal vehicle control. Thus, long-term supplementation of
      1,25(OH)(2)D(3) significantly (P < 0.001) inhibits hepatic cytosolic lipid
      peroxidation, thereby protecting the cell membranes from free-radical mediated
      damage. These results suggest that 1,25(OH)(2)D(3) is useful in the inhibition of
      rat liver carcinogenesis.

PMID- 11241676
TI  - Specific growth factors during the expansion and redifferentiation of adult human
      articular chondrocytes enhance chondrogenesis and cartilaginous tissue formation
      in vitro.
AB  - Adult human articular chondrocytes were expanded in a medium with 10% serum (CTR)
      or further supplemented with different mitogens (i.e., EGF, PDGFbb, FGF-2, TGF
      beta 1, or FGF-2/TGF beta 1). Cells were then induced to redifferentiate in 3D
      pellets using serum-supplemented medium (SSM), serum-free medium (SFM), or SFM
      supplemented with factors inducing differentiation of chondroprogenitor cells
      (i.e., TGF beta 1 and/or dexamethasone). All factors tested during expansion
      enhanced chondrocyte proliferation and dedifferentiation, as assessed by the mRNA
      ratios of collagen type II to type I (CII/CI) and aggrecan to versican (Agg/Ver),
      using real-time PCR. FGF-2/TGF beta 1-expanded chondrocytes displayed the lowest
      doubling times, CII/CI and Agg/Ver ratios, averaging, respectively, 50, 0.2 and
      15% of CTR-expanded cells. Redifferentiation in pellets was more efficient in SFM
      than SSM only for EGF-, PDGFbb- or FGF-2-expanded chondrocytes. Upon
      supplementation of SFM with TGF beta and dexamethasone (SFM TD), CII/CI ratios
      decreased 4.4-fold for EGF- and PDGFbb-expanded chondrocytes, but increased 96
      fold for FGF-2/TGF beta 1-expanded cells. Chondrocytes expanded with FGF-2/TGF
      beta 1 and redifferentiated in SFM TD expressed the largest mRNA amounts of CII
      and aggrecan and generated cartilaginous tissues with the highest accumulation of
      glycosaminoglycans and collagen type II. Our results provide evidence that growth
      factors during chondrocyte expansion not only influence cell proliferation and
      differentiation, but also the cell potential to redifferentiate and respond to
      regulatory molecules upon transfer into a 3D environment.

PMID- 11241677
TI  - Introduction to this issue: youth violence.

PMID- 11241678
TI  - Race, youth violence, and the changing jurisprudence of waiver.
AB  - This article analyzes the legal history and jurisprudential theory of legislative
      offense-exclusion and prosecutorial waiver laws over the past quarter-century.
      Initially concerns about racial discrimination and civil rights motivated the
      Supreme Court in Kent v. United States to require due process in judicial waiver
      hearings. Offense-exclusion and "direct file" laws evolved and expanded in direct
      reaction to Kent as lawmakers sought simple and expedient alternatives to
      judicial waiver hearings. The "just deserts" sentencing movement of the 1970s,
      which advocated determinate and presumptive offense-based sentences, provided a
      conceptual alternative to judicial discretion and a jurisprudential rationale for
      offense exclusion laws. Research on delinquent and criminal careers in the 1970s,
      which initially promised empirically grounded selective incapacitation sentencing
      strategies, provided another conceptual foundation for offense-based waiver laws
      that focused on youths' prior records. Finally, offense exclusion provided a
      politically attractive strategy for "get tough" public officials who proposed to
      "crack down" on "baby boom" increases in youth crime. The jurisprudential shift
      in sentencing emphases from considerations of the offender to characteristics of
      the offense relocated waiver and sentencing discretion from judges to
      prosecutors. By the early 1990s, as a result of political "crack-downs" on youth
      crime, the scope of excluded offense legislation increased substantially, became
      overly inclusive and excessively rigid, and exhibited many of the negative
      features associated with mandatory sentencing laws.

PMID- 11241679
TI  - Is it inherently prejudicial to try a juvenile as an adult?
AB  - Given only information that a youth who could have been tried as either an adult
      or as a juvenile was being tried as an adult for murder, 218 undergraduate mock
      jurors were able to form consistent impressions of the defendant. A very high
      percent of our mock jurors included a criminal or juvenile justice history as
      part of that impression. A very large majority of the mock jurors also said that
      knowledge of that criminal history would be relevant to their vote of guilty.
      Almost all mock jurors said they would be influenced toward voting guilty by
      knowledge of a previous criminal history. Few of the other components of the
      impression were so closely correlated with a judgment of relevance, or with a
      judgment that they would be influenced toward voting guilty by the knowledge of
      that component of the stereotype. The effect is relatively specific to knowledge
      of a previous criminal history. The study has limited ecological validity.
      Nonetheless, we raise questions about whether the fact that a youth is put on
      trial as an adult is inherently prejudicial, and violates the Sixth Amendment
      right to an impartial jury.

PMID- 11241680
TI  - Reactions to youth crime: perceptions of accountability and competency.
AB  - Recent changes in juvenile justice policies have stimulated debate among legal
      professionals and social scientists. As such, public opinion concerning juvenile
      offenders is an important and timely topic for empirical study. In the present
      study, respondents read a scenario about a juvenile who committed a crime, and
      then decided on a sentence and rated perceptions of the juvenile's accountability
      and legal competence. Four between-subject factors were manipulated: age of the
      defendant (11 versus 14 versus 17 years), type of crime (shooting versus arson),
      crime outcome (victim injured versus died), and time delay between the
      instigating incident and the crime (immediately versus one day). The type and
      outcome of the crime were major motivating factors in sentencing decisions and
      perceptions of legal competence, and, although younger offenders were seen as
      less accountable and less competent than older offenders, sentence allocation and
      attitudes towards punishment were not significantly affected by offender age.

PMID- 11241681
TI  - Assessment of "juvenile psychopathy" and its association with violence: a
      critical review.
AB  - Interest in the construct of psychopathy as it applies to children and
      adolescents has become an area of considerable research interest in the past 5-10
      years, in part due to the clinical utility of psychopathy as a predictor of
      violence among adult offenders. Despite interest in "juvenile psychopathy" in
      general and its relationship to violence in particular, relatively few studies
      specifically have examined whether operationalizations of this construct among
      children and adolescents predict various forms of aggression. This article
      critically reviews this literature, as well as controversies regarding the
      assessment of adult psychopathic "traits" among juveniles. Existing evidence
      indicates a moderate association between measures of psychopathy and various
      forms of aggression, suggesting that this construct may be relevant for purposes
      of short-term risk appraisal and management among juveniles. However, due to the
      enormous developmental changes that occur during adolescence and the absence of
      longitudinal research on the stability of this construct (and its association
      with violence), we conclude that reliance on psychopathy measures to make
      decisions regarding long-term placements for juveniles is contraindicated at this
      time.

PMID- 11241682
TI  - Personality features and characteristics of violent events committed by juvenile
      offenders.
AB  - The present study investigated the relationship between characteristics of a
      violent event, as self-reported by 82 incarcerated juvenile offenders, and
      personality features measured by the Millon Adolescent Clinical Inventory (MACI).
      The study predicted that specific personality features that have previously been
      associated with psychopathy would be associated with the instrumentality,
      emotional reactivity, and empathy or guilt reported for the incident. Results
      confirmed that a self-reported pattern of elevated instrumental motivation and
      reduced empathy or guilt was associated with higher scores on the MACI Forceful,
      Unruly, Substance Abuse Proneness, Impulsive Propensity, and Family Discord
      Scales, as well as a recently developed Psychopathy Content Scale. Self-reported
      elevated instrumental motivation and reduced empathy or guilt was also associated
      with lower scores on the Submissive, Conforming, Anxious Feelings, and Sexual
      Discomfort Scales. There were no significant relationships observed between
      emotional reactivity and personality scales.

PMID- 11241683
TI  - Who's in, who's out, and who's back: follow-up data on 59 juveniles incarcerated
      in adult prison for murder or attempted murder in the early 1980s.
AB  - Since the mid-1980s, when juvenile arrests for violent crime increased
      dramatically, interest has focused on juvenile offenders who commit violent acts.
      Legislatures across the United States have enacted a variety of measures to "get
      tough" with juveniles in response to escalating crime rates and the perceptions
      that longer sentences were needed. This manuscript provides follow-up data on 59
      juveniles who were committed to the adult Department of Corrections in Florida
      during the period January 1982 through January 1984 for one or more counts of
      murder, attempted murder, or, in a few cases, manslaughter. Although many of
      these adolescents received lengthy prison sentences, more than two-thirds had
      been released from prison prior to November 1999. This article presents data on
      amount of time served and recidivism over the 15 to 17 year period. Results
      indicated that 60 percent of sample subjects released from prison were returned
      to prison, and most of those who failed did so within the first three years of
      release. Findings from the present study, when examined in the context of
      previous comparative follow-up studies of delinquent youths, suggest that the
      dialogue on how to handle violent youths must be continued if juvenile homicide
      offenders are going to be released to society at some point in the future.

PMID- 11241685
TI  - Juvenile curfews: are they an effective and constitutional means of combating
      juvenile violence?
AB  - Curfew ordinances have become a popular way to attempt to combat juvenile crime
      and victimization. Although the Supreme Court has yet to hear a curfew case,
      several constitutional challenges have been brought in lower federal courts. The
      cases are replete with psychological assumptions for which there is limited
      empirical evidence. In applying the "strict scrutiny" standard, several courts
      have also questioned whether juvenile curfews are narrowly tailored to further
      the State's interest in reducing juvenile crime and victimization. While public
      opinion and reports from several police jurisdictions support the utility of
      juvenile curfews, recent empirical studies indicate that curfews are not
      effective at reducing juvenile offending or victimization. This paper argues that
      the emerging evidence does not support the use of juvenile curfews and urges
      policy makers and the courts to examine the efficacy of curfew legislation.
      Directions for future research that could be helpful to the courts in applying
      the Bellotti factors to curfew cases are also suggested.

PMID- 11241684
TI  - Self-other representations and relational and overt aggression in adolescent
      girls and boys.
AB  - Aggressive behavior in girls has received far less attention than similar
      problems in boys. This study examined self-representation, and others'
      representation of self, as predictors of relational aggression, overt aggression,
      and assaultive behavior in 32 girls and 52 boys, 10 to 17 years of age, referred
      for assessment due to significant aggressive and delinquent behavior problems. As
      predicted, negativity of self-representation predicted relational aggression in
      girls but not boys. Negativity of self-representation also predicted overt
      aggression and assaultive behavior in both girls and boys. Parental
      representations of self were not predictive in this sample; however, negativity
      of peer representations of self, was associated with increased relational
      aggression in girls and decreased relational aggression in boys. Negativity of
      peer representations of self also predicted overt aggression and assaultive
      behavior in both girls and boys. Results suggest that the evaluation of self
      other representations may be valuable in the assessment of risk for gender
      specific patterns of aggression.

PMID- 11241686
TI  - The United Nations Convention on the Rights of the Child: a basis for jus cogens
      prohibition of juvenile capital punishment in the United States.
AB  - This article supports the position that the 1989 United Nations Convention on the
      Rights of the Child (CRC) articulates a prohibition of capital punishment of
      juveniles that now must be considered a norm of jus cogens. The article provides
      statistics and trends regarding juveniles who commit capital crimes and describes
      how the U.S. justice system handles such juveniles, including Eighth Amendment
      analyses of juvenile executions under the U.S. Constitution. The article also
      discusses community consensus regarding evolving standards of decency, describes
      international law on the capital punishment of juveniles, and outlines worldwide
      trends in juvenile executions. It then defines and describes the concepts of
      customary international law and jus cogens, applying these concepts to the
      problem of the execution of juveniles in the United States. The article concludes
      by suggesting that there is a moral imperative for universal prohibition of
      juvenile capital punishment and by speculating about the domestic effects of
      applying such a jus cogens norm in the United States.

PMID- 11241687
TI  - An analysis of the argument that clinicians under-predict sexual violence in
      civil commitment cases.
AB  - This paper presents the results of an analysis that evaluated the assumptions and
      arguments set forth in a recent paper (Doren, 1998), which concluded that
      clinicians under-predict the risk that candidates for commitment as dangerous sex
      offenders will recidivate. This analysis indicates that such a conclusion is
      untenable because almost all of the assertions on which it is based might be
      disputed in one way or another. These flaws undermine the paper's value as a
      source of secondary authority in hearings pertaining to the commitment of
      dangerous sex offenders. Nonetheless, its publication will probably be beneficial
      for professional practice in this arena because it raises several important
      issues that stand in need of resolution.

PMID- 11241688
TI  - Analyzing the analysis: a response to Wollert (2000).
AB  - In a thoughtful critique in the article preceding this one, many arguments are
      presented about the veracity of assumptions and conclusions I made in my 1998
      publication concerning the sexual recidivism base rates for certain incarcerated
      sex offenders. This article responds to some of the issues raised. First, the
      ultimate conclusion of the preceding critique is assessed. Even when assuming the
      accuracy of all points made in the preceding article, an analysis described
      herein still demonstrates that the current U.S.A. civil commitment referral
      procedures "under-predict" sexual recidivism rates. Second, an inference made in
      the preceding critique, read as a possible implication from my article, is
      strongly contested. Finally, the remaining discussion responds to various other
      concerns that were raised. While scientific exploration of issues is typically
      expected to lead to occasional professional differences, a significant lack of
      agreement with the preceding critique is found.

PMID- 11241689
TI  - Study of tricarboxylic acid cycle flux changes in human visual cortex during
      hemifield visual stimulation using (1)H-[(13)C] MRS and fMRI.
AB  - The relationships between brain activity and accompanying hemodynamic and
      metabolic alterations, particularly between the cerebral metabolic rate of oxygen
      utilization (CMR(O2)) and cerebral blood flow (CBF), are not thoroughly
      established. CMR(O2) is closely coupled to the rate of tricarboxylic acid (TCA)
      cycle flux. In this study, the changes in glutamate labeling during (13)C labeled
      glucose administration were determined in the human brain as an index of
      alterations in neuronal TCA cycle turnover during increased neuronal activity.
      Two-volume (1)H-[(13)C] MR spectroscopy (MRS) of the visual cortex was combined
      with functional MRI (fMRI) at 4 Tesla. Hemifield visual stimulation was employed
      to obtain data simultaneously from activated and control regions located
      symmetrically in the two hemispheres of the brain. The results showed that the
      fractional change in the turnover rate of C4 carbon of glutamate was less than
      that of CBF during visual stimulation. The fractional changes in CMR(O2) (Delta
      CMR(O2)) induced by activation must be equal to or less than the fractional
      change in glutamate labeling kinetics. Therefore, the results impose an upper
      limit of approximately 30% for Delta CMR(O2) and demonstrate: 1) that fractional
      CBF increases exceed Delta CMR(O2) during elevated activity in the visual cortex,
      and 2) that such an unequal change would explain the observed positive blood
      oxygenation level dependent (BOLD) effect in fMRI. Magn Reson Med 45:349-355,
      2001.

PMID- 11241690
TI  - fMRI of auditory stimulation with intermolecular double-quantum coherences
      (iDQCs) at 1.5T.
AB  - An intermolecular double-quantum coherence (iDQC) imaging technique was used to
      study auditory activation in the human brain at 1.5T with a dual temporal lobe
      surface phased array coil and a quadrature head coil. Preliminary results
      demonstrate that it is feasible to obtain auditory activation maps using iDQC
      imaging at 1.5T, both in individual subjects using the surface coil array and
      with multisubject averaging of data using the head coil. The most robust
      activation map was obtained when a spin-echo (SE) acquisition was combined with
      an iDQC excitation. Since SE with conventional single quantum coherence (SQC) and
      similar parameters showed much reduced activation in spite of its higher signal
      to-noise ratio (SNR), it was determined that activation resulting from the SE
      iDQC acquisition almost entirely originates from iDQCs. In addition, the fact
      that the robust activation was obtained using signals at an evolution time more
      sensitive to changes in magnetic susceptibilities also suggests the sensitivity
      of iDQCs to the BOLD effect upon activation. iDQCs provide a novel MRI method
      which is potentially more sensitive to the BOLD effect traditionally measured
      with SQC. Magn Reson Med 45:356-364, 2001.

PMID- 11241691
TI  - Registered (1)H and (3)He magnetic resonance microscopy of the lung.
AB  - Using in vivo magnetic resonance microscopy, registered (1)H and hyperpolarized
      (3)He images of the rat lung were obtained with a resolution of 0.098 x 0.098 x
      0.469 mm (4.5 x 10(-3) mm(3)). The requisite stability and SNR was achieved
      through an integration of scan-synchronous ventilation, dual-frequency RF coils,
      anisotropic projection encoding, and variable RF excitation. The total
      acquisition time was 21 min for the (3)He images and 64 min for the (1)H image.
      Airways down to the 6th and 7th orders are clearly visible. Magn Reson Med 45:365
      370, 2001.

PMID- 11241692
TI  - Rapid ventricular assessment using real-time interactive multislice MRI.
AB  - A multislice real-time imaging technique is described which can provide
      continuous visualization of the entire left ventricle under resting and stress
      conditions. Three dynamically adjustable slices containing apical, mid, and base
      short axis views are imaged 16 times/sec (48 images/sec), with each image
      providing 3.12 mm resolution over a 20 cm field of view. Initial studies indicate
      that this technique is useful for the assessment of LV function by providing
      simultaneous real-time visualization of all 16 wall segments. This technique may
      also be used for stress LV function and, when used in conjunction with contrast
      agents, myocardial perfusion imaging. Magn Reson Med 45:371-375, 2001.

PMID- 11241693
TI  - High-temperature superconducting surface coil for in vivo microimaging of the
      human skin.
AB  - A small, high-temperature superconducting (HTS) surface coil was used to improve
      the signal-to-noise ratio (SNR) for in vivo human skin microscopy at 1.5 T. The
      internal noise of the conventional copper coil limits the SNR for this
      application. Inductive measurements of the HTS coil parameters indicated that at
      77 K its internal noise contributed about 4% of the total noise, and the
      predicted SNR gain was about 3.2-fold over that of a room-temperature copper
      coil. In vivo images of the human skin produced with the HTS coil showed highly
      resolved details and a 3.7-fold improvement in SNR over that obtained with the
      room-temperature copper coil. Magn Reson Med 45:376-382, 2001.

PMID- 11241694
TI  - Changes in apparent diffusion coefficients of metabolites in rat brain after
      middle cerebral artery occlusion measured by proton magnetic resonance
      spectroscopy.
AB  - Diffusion-weighted proton MR spectroscopy and imaging have been applied to a rat
      brain model of unilateral middle cerebral artery occlusion between 1 and 4 hr
      post occlusion. Similar apparent diffusion coefficients (ADC) of most metabolites
      were observed within each hemisphere. In the ischemic ipsilateral hemisphere, the
      ADCs were (0.083--0.116). 10(-3) mm(2)/sec for lactate (Lac), alanine (Ala),
      gamma-amino butyric acid (GABA), N-acetyl aspartate (NAA), glutamine (Gln),
      glutamate (Glu), total creatine (tCr), choline-containing compounds (Cho), and
      myo-inositol (Ins), in the contralateral hemisphere (0.138--0.158). 10(-3)
      mm(2)/sec for NAA, Glu, tCr, Cho, and Ins. Higher ADCs was determined for taurine
      (Tau) in the ipsilateral (0.144. 10(-3) mm(2)/sec) and contralateral (0.198. 10(
      3) mm(2)/sec) hemisphere. In the ischemic hemisphere, a relative ADC decrease to
      65--75% was observed for NAA, Glu, tCr, Cho, Ins and Tau, which was similar to
      the decrease of the water ADC (to 67%). The results suggest a common cause of the
      observed ADC changes and provide a broader experimental basis to evaluate
      theories of water and metabolite diffusion. Magn Reson Med 45:383-389, 2001.

PMID- 11241695
TI  - Postprocessing method to segregate and quantify the broad components underlying
      the phosphodiester spectral region of in vivo (31)P brain spectra.
AB  - In a typical, in vivo (31)P brain spectrum, the phosphomonoester (PME) and
      phosphodiester (PDE) spectral region not only contains signals from freely mobile
      PMEs and PDEs (which are anabolic and catabolic products of membrane
      phospholipids) but also signals of broader underlying lineshapes from less-mobile
      molecules. In general, either the PME and PDE resonances are quantified as a
      combined value of freely mobile metabolites plus less-mobile molecules or the
      broader underlying signal is reduced/eliminated prior to or post data collection.
      In this study, a postprocessing method that segregates and quantifies the
      individual contributions of the freely mobile metabolites and the less-mobile
      molecules is introduced. To demonstrate the precision and accuracy of the method,
      simulated data and in vivo (31)P brain spectroscopy data of healthy individuals
      were quantified. The ability to segregate and quantify these various PME and PDE
      contributions provides additional spectral information and improves the accuracy
      of the interpretation of (31)P spectroscopy results. Magn Reson Med 45:390-396,
      2001.

PMID- 11241696
TI  - Vessel size imaging.
AB  - Vessel size imaging is a new method that is based on simultaneous measurement of
      the changes Delta R(2) and Delta R(2)(*) in relaxation rate constants induced by
      the injection of an intravascular superparamagnetic contrast agent. Using the
      static dephasing approximation for Delta R(2)(*) estimation and the slow
      diffusion approximation for Delta R(2) estimation, it is shown that the ratio
      Delta R(2)/Delta R(2)(*) can be expressed as a function of the susceptibility
      difference between vessels and brain tissue, the brain water diffusion
      coefficient, and a weighted mean of vessel sizes. Comparison of the results with
      1) the Monte Carlo simulations used to quantify the relationship between tissue
      parameters and susceptibility contrast, 2) the experimental MRI data in the
      normal rat brain, and 3) the histologic data establishes the validity of this
      approach. This technique, which allows images of a weighted mean of the vessel
      size to be obtained, could be useful for in vivo studies of tumor
      vascularization. Magn Reson Med 45:397-408, 2001.

PMID- 11241697
TI  - In vivo measurement of the size of lipid droplets in an intracerebral glioma in
      the rat.
AB  - Pulsed field gradient NMR was used to measure the root mean square displacement
      lambda of the NMR visible lipid molecules in C6 brain tumors in the rat at
      different diffusion times. For a distribution of spherical droplets of diameter
      with volume fraction xi(Phi(i)), the mean characteristic droplet diameter Phi(c)
      = square root of Sigma(i)xi(Phi(i)Phi(i)(2) was shown to be related to the root
      mean square displacement at long diffusion times by the simple relationship
      Phi(c)(2) = 10 lambda(2). In the range of diffusion times 100--530 msec, lambda
      was found to be independent of the diffusion time and equal to 1.35 +/- 0.22
      microm and Phi(c) to 4.27 +/- 0.71 microm. The data reinforce the notion that the
      presence of lipid resonances in NMR spectra of tumors is due to lipid droplets.
      Light microscopy of histologic slices showed the presence of lipid droplets
      mainly in the necrotic region and in a layer of tumor cells surrounding the
      necrosis. Magn Reson Med 45:409-414, 2001.

PMID- 11241698
TI  - MR properties of rat sciatic nerve following trauma.
AB  - T(1) and T(2) relaxation times, magnetization transfer (MT), and diffusion
      anisotropy of rat sciatic nerve were measured at different time intervals
      following trauma. The nerve injury was induced by either cutting (irreversible
      nerve degeneration) or crushing (degeneration followed by regeneration). The MR
      properties were measured for proximal and distal portions of the injured nerve.
      The portions of the nerve proximal to the induced injury exhibited MR
      characteristics similar to those of normal nerves, whereas the distal portions
      showed significant differences in all MR parameters. These differences diminished
      in the regenerating nerves within approximately 4 weeks post injury. In the case
      of irreversible nerve damage, the differences in the distal nerves were slightly
      larger and did not resolve even 6 weeks after induced trauma. The MR measurements
      were correlated with histopathology exams. Observed changes in tissue
      microstructure, such as demyelination, inflammation, and axonal loss, can result
      in a significant increase in the average T(1) and T(2) relaxation times,
      reduction in the MT effect, and decrease in diffusion anisotropy. MR parameters,
      therefore, are very good indicators of nerve damage and may be useful in
      monitoring therapies that assist nerve regeneration. Magn Reson Med 45:415-420,
      2001.

PMID- 11241699
TI  - Measurements of hyperpolarized gas properties in the lung. Part III: (3)He T(1).
AB  - Hyperpolarized (3)He spin-lattice relaxation was investigated in the guinea pig
      lung using spectroscopy and imaging techniques with a repetitive RF pulse series.
      T(1) was dominated by interactions with oxygen and was used to measure the
      alveolar O(2) partial pressure. In animals ventilated with a mixture of 79% (3)He
      and 21% O(2), T(1) dropped from 19.6 sec in vivo to 14.6 sec after cardiac
      arrest, reflecting the termination of the intrapulmonary gas exchange. The
      initial difference in oxygen concentration between inspired and alveolar air, and
      the temporal decay during apnea were related to functional parameters. Estimates
      of oxygen uptake were 29 +/- 11 mL min(-1) kg(-1) under normoxic conditions, and
      9.0 +/- 2.0 mL min(-1) kg(-1) under hypoxic conditions. Cardiac output was
      estimated to be 400 +/- 160 mL min(-1) kg(-1). The functional residual capacity
      derived from spirometric magnetic resonance experiments varied with body mass
      between 5.4 +/- 0.3 mL and 10.7 +/- 1.1 mL. Magn Reson Med 45:421-430, 2001.

PMID- 11241700
TI  - Perfusion-weighted imaging of interictal hypoperfusion in temporal lobe epilepsy
      using FAIR-HASTE: comparison with H(2)(15)O PET measurements.
AB  - To detect perfusion abnormalities in areas of high magnetic susceptibility in the
      brain, an arterial spin-labeling MRI technique utilizing flow-sensitive
      alternating inversion recovery (FAIR) and half-Fourier single shot turbo spin
      echo (HASTE) for spin preparation and image acquisition, respectively, was
      developed. It was initially tested in a functional study involving visual
      stimulation, and was able to detect significant activation with an increase
      (approximately 70%) in relative cerebral blood flow. Subsequently, it was applied
      in a clinical situation in eight patients with temporal lobe epilepsy (TLE). The
      perfusion-weighted images obtained showed no susceptibility artifacts even in the
      region of the inferior temporal lobe and were able to detect interictal
      hypoperfusion in TLE. The results were compared with those derived from H(2)(15)O
      PET perfusion imaging in each patient. A statistically significant correlation (r
      = 0.75, P < 0.05) was found between results acquired from these two modalities.
      Magn Reson Med 45:431-435, 2001.

PMID- 11241701
TI  - TmDOTP(5-) as a (23)Na shift reagent for the subcutaneously implanted 9L
      gliosarcoma in rats.
AB  - The use of TmDOTP(5-) as an in vivo (23)Na NMR shift reagent (SR) for
      subcutaneously implanted 9L gliosarcoma was evaluated. TmDOTP(5-) produced a
      single sharp extracellular peak after about 50-60 min of infusion, and did not
      cause any changes in the (31)P resonance areas or chemical shifts, suggesting
      that the SR is homogeneously distributed in the extracellular space and does not
      alter tumor bioenergetic status. TmDOTP(5-) and CoEDTA(-) as extracellular space
      markers gave identical results for relative extracellular space (0.25 +/- 0.03
      and 0.25 +/- 0.04, respectively) and intracellular Na(+) concentration (19.3 +/-
      4.0 mM and 18.6 +/- 3.9 mM, respectively), indicating that the biodistribution of
      the SR is the same as the well-accepted extracellular space marker. The in vivo
      T(1) and T(2) relaxation times of intra- and extracellular Na(+) were also
      measured. Our results indicate that TmDOTP(5-) promises to be an effective shift
      reagent and extracellular space marker in the 9L gliosarcoma and perhaps other
      tumors. Magn Reson Med 45:436-442, 2001.

PMID- 11241702
TI  - Regional sensitivity and coupling of BOLD and CBV changes during stimulation of
      rat brain.
AB  - Functional MRI of rat brain was performed at 2 Tesla following intravenous
      injection of cocaine in order to 1) determine if changes in CBV and changes in
      BOLD signal were regionally coupled in brain parenchyma, and 2) compare the
      sensitivities of these imaging methods across different brain structures. Percent
      changes in CBV and BOLD relaxation rate were spatially and temporally coupled
      during this graded brain activation. The use of contrast agent increased
      functional sensitivity in all parenchymal brain structures, with a strong but
      predictable dependence on the resting-state blood volume fraction. Magn Reson Med
      45:443-447, 2001.

PMID- 11241703
TI  - Noise correction for the exact determination of apparent diffusion coefficients
      at low SNR.
AB  - Noise in MR image data increases the mean signal intensity of image regions due
      to the usually performed magnitude reconstruction. Diffusion-weighted imaging
      (DWI) is especially affected by high noise levels for several reasons, and a
      decreasing SNR at increasing diffusion weighting causes systematic errors when
      calculating apparent diffusion coefficients (ADCs). Two different methods are
      presented to correct biased signal intensities due to the presence of complex
      noise: 1) with Gaussian intensity distribution, and 2) with arbitrary intensity
      distribution. The performance of the correction schemes is demonstrated by
      numerical simulations and DWI measurements on two different MR systems with
      different noise characteristics. These experiments show that noise significantly
      influences the determination of ADCs. Applying the proposed correction schemes
      reduced the bias of the determined ADC to less than 10% of the bias without
      correction. Magn Reson Med 45:448-453, 2001.

PMID- 11241704
TI  - 3D-micro-MR angiography of mice using macromolecular MR contrast agents with
      polyamidoamine dendrimer core with reference to their pharmacokinetic properties.
AB  - Four novel macromolecular MRI contrast agents, all of which had the same chemical
      composition but different molecular weights, were prepared using generation-3, 
      4, -5, and -6 polyamidoamine (PAMAM) dendrimers conjugated with a bifunctional
      diethylenetriaminepentaacetic acid derivative to change the blood retention,
      tissue perfusion, and excretion. Size-dependent changes in the pharmacokinetics
      were observed in the biodistribution study. (153)Gd-labeled generation-6 PAMAM
      conjugates remained in the blood significantly longer than all of the other
      preparations (P < 0.001). The increase in blood-to-organ ratio of the
      preparations was found to correlate with increasing molecular size (P < 0.001).
      Additionally, 3D-micro MR images and angiography of mice of high quality and
      detail were obtained using PAMAM-(1B4M-Gd)x as a macro-molecular MRI contrast
      agent with a 1.5-T clinical MRI instrument. Numerous fine vessels of
      approximately 200 microm diameter were visualized on subtracted 3D-MR
      angiographms with G6D-(1B4M-Gd)(192). The quality of the images was sufficient to
      estimate the microvasculature of cancerous tissue for anti-angiogenesis therapy
      and to investigate knockout mice. Magn Reson Med 45:454-460, 2001.

PMID- 11241705
TI  - Fast measurements of the motion and velocity spectrum of blood using MR tagging.
AB  - A new method is presented for tracking the motion of blood and determining its
      velocity spectrum from magnetic resonance data collected within a single
      heartbeat. The method begins by tagging a column of blood in a vessel by
      combining a 1D SPAMM excitation with a 2D cylindrical excitation. A series of 1D
      projections of the tagging pattern is acquired from a train of gradient echoes.
      The influence of specific excitation profiles and velocity profiles on the motion
      of the tags is explored for steady flow. It is shown mathematically, and
      confirmed with phantom experiments, that the velocity of a tag equals the mean
      velocity of the excited fluid when the velocity spectrum is symmetric about its
      mean velocity. The velocity spectrum is derived by analyzing the interference
      between tags moving at different velocities. This appears to be the first use of
      magnitude tagging to obtain velocity spectra. Representative measurements in a
      human aorta are presented to assess feasibility in vivo. Magn Reson Med 45:461
      469, 2001.

PMID- 11241706
TI  - Sensitivity and performance time in MRI dephasing artifact reduction methods.
AB  - Although shimming can improve static field inhomogeneity, local field
      imperfections induced by tissue susceptibility differences cannot be completely
      corrected and can cause substantial signal loss in gradient echo images through
      intravoxel dephasing. Dephasing increases with voxel size so that one simple
      method of reducing the effect is to use thin slices. Signal-to-noise ratio (SNR)
      can then be increased by averaging over the subslices to form the final, thick
      slice. We call this method subslice averaging or SSAVE. Alternatively, a range of
      different amplitude slice select rephase gradients can be used to compensate for
      different susceptibility induced gradient offsets. The final image can then be
      formed by combining individual images in a variety of ways: summation, summation
      of the squares of the images, forming the maximum intensity projection of the
      image set, and Fourier transformation followed by summation. We show here that,
      contrary to previous claims, the theoretical sensitivity (i.e., SNR divided by
      the square root of the imaging time) of all these alternative methods is very
      similar. However, performance time (i.e., minimum-imaging time) of the simplest
      method, SSAVE, is much shorter than that of alternatives. This is confirmed
      experimentally on phantoms and anesthetized mice. Magn Reson Med 45:470-476,
      2001.

PMID- 11241707
TI  - Correcting partial volume artifacts of the arterial input function in
      quantitative cerebral perfusion MRI.
AB  - To quantify cerebral perfusion with dynamic susceptibility contrast MRI (DSC
      MRI), one needs to measure the arterial input function (AIF). Conventionally, one
      derives the contrast concentration from the DSC sequence by monitoring changes in
      either the amplitude or the phase signal on the assumption that the signal arises
      completely from blood. In practice, partial volume artifacts are inevitable
      because a compromise has to be reached between the temporal and spatial
      resolution of the DSC acquisition. As the concentration of the contrast agent
      increases, the vector of the complex blood signal follows a spiral-like
      trajectory. In the case of a partial-volume voxel, the spiral is located around
      the static contribution of the surrounding tissue. If the static contribution of
      the background tissue is disregarded, estimations of the contrast concentration
      will be incorrect. By optimizing the correspondence between phase information and
      amplitude information one can estimate the origin of the spiral, and thereupon
      correct for partial volume artifacts. This correction is shown to be accurate at
      low spatial resolutions for phantom data and to improve the AIF determination in
      a clinical example. Magn Reson Med 45:477-485, 2001.

PMID- 11241708
TI  - Automatic scan prescription for brain MRI.
AB  - Diagnostic brain MRI scans are usually performed by trained medical technologists
      who manually prescribe the position and orientation of a scanning volume. In this
      study, a fully automatic computer algorithm is described which compensates for
      variable patient positioning and acquires brain MRI scans in a predefined
      reference orientation. The method involves acquiring a rapid water-only pilot
      scan, segmenting the brain surface, and matching it to a reference surface. The
      inverse matching transformation is then used to adapt a geometric description of
      the desired scanning volume, defined relative to the reference surface, to the
      current patient. Both pilot scan and processing are performed within 30 sec. The
      method was tested in 25 subjects, and consistently recovered orientation
      differences between the reference and each subject to within +/-5 degrees.
      Compared to manual prescription, automatic scan prescription promises many
      potential benefits, including reduced scan times, reproducible scan orientations
      along anatomically preferable orientations, and better reproducibility for
      longitudinal studies. Magn Reson Med 45:486-494, 2001.

PMID- 11241709
TI  - Specific coil design for SENSE: a six-element cardiac array.
AB  - In sensitivity encoding (SENSE), the effects of inhomogeneous spatial sensitivity
      of surface coils are utilized for signal localization in addition to common
      Fourier encoding using magnetic field gradients. Unlike standard Fourier MRI,
      SENSE images exhibit an inhomogeneous noise distribution, which crucially depends
      on the geometrical sensitivity relations of the coils used. Thus, for optimum
      signal-to-noise-ratio (SNR) and noise homogeneity, specialized coil
      configurations are called for. In this article we study the implications of SENSE
      imaging for coil layout by means of simulations and imaging experiments in a
      phantom and in vivo. New, specific design principles are identified. For SENSE
      imaging, the elements of a coil array should be smaller than for common phased
      array imaging. Furthermore, adjacent coil elements should not overlap. Based on
      the findings of initial investigations, a configuration of six coils was designed
      and built specifically for cardiac applications. The in vivo evaluation of this
      array showed a considerable SNR increase in SENSE images, as compared with a
      conventional array. Magn Reson Med 45:495-504, 2001.

PMID- 11241710
TI  - Stream function optimization for gradient coil design.
AB  - This work presents a method applied to the design of short self-shielded gradient
      coils of cylindrical geometry. The method uses a hybrid technique that combines
      the simulated annealing and target field methods to optimize the standard stream
      functions. The optimized stream functions were parameterized using a few degrees
      of freedom to reduce the computing time. The optima stream function parameters
      are given for easy coil design purposes. The proposed approach is compared to the
      target field method. The main advantage of the present method over the target
      field method is its ability to enlarge the homogeneous gradient volume. In
      addition, the designs of short coils based on this approach have shown lower
      inductance than the coil design based on the target field method. The fast
      simulated annealing technique presented in this work enables the gradient coil
      optimization in less than 3 min of computing time. Magn Reson Med 45:505-512,
      2001.

PMID- 11241711
TI  - Reanalysis of multislice (1)H MRSI in amyotrophic lateral sclerosis.
AB  - The goal of this work was to reexamine previously published (1) brain
      spectroscopy data of abnormal metabolite ratios in amyotrophic lateral sclerosis
      (ALS). Toward this goal, (1)H MR spectroscopic imaging data from 10 ALS and nine
      control subjects were reanalyzed using improved data analysis techniques,
      including automated curve fitting and tissue-volume correction. In the motor
      cortex of ALS, N-acetyl aspartate (NAA) was 23% (P = 0.004) lower than in
      controls, and in the posterior internal capsule of ALS choline compounds (Cho)
      were 20% (P = 0.02) higher. This demonstrates that the metabolite ratio changes
      in ALS were due to NAA loss in the motor cortex (as expected) and Cho increase in
      the posterior internal capsule (not expected). Magn Reson Med 45:513-516, 2001.

PMID- 11241712
TI  - Brain GABA editing without macromolecule contamination.
AB  - A new scheme is proposed to edit the 3.0 ppm GABA resonance without macromolecule
      (MM) contamination. Like previous difference spectroscopy approaches, the new
      scheme manipulates J-modulation of this signal using a selective editing pulse.
      The elimination of undesirable MM contribution at 3.0 ppm is obtained by applying
      this pulse symmetrically about the J-coupled MM resonance, at 1.7 ppm, in the two
      steps of the editing scheme. The effectiveness of the method is demonstrated in
      vitro, using lysine to mimic MM, and in vivo. As compared to the most commonly
      used editing scheme, which necessitates the acquisition and processing of two
      distinct difference spectroscopy experiments, the new scheme offers a reduction
      in experimental time (-33%) and an increase in accuracy. Magn Reson Med 45:517
      520, 2001.

PMID- 11241713
TI  - Efficient off-resonance correction for spiral imaging.
AB  - A new spiral imaging technique incorporates the acquisition of a field map into
      imaging interleaves. Variable density spiral trajectories are designed to
      oversample the central region of k-space, and interleaves are acquired at two
      different echo times. A field map is extracted from this data and multifrequency
      reconstruction is used to form an off-resonance corrected image using the entire
      dataset. Simulation, phantom, and in vivo results indicate that this technique
      can be used to achieve higher image and/or field map spatial resolution compared
      to conventional techniques. Magn Reson Med 45:521-524, 2001.

PMID- 11241714
TI  - Optimized distortion correction technique for echo planar imaging.
AB  - A new phase-shifted EPI pulse sequence is described that encodes EPI phase errors
      due to all off-resonance factors, including B(o) field inhomogeneity, eddy
      current effects, and gradient waveform imperfections. Combined with the
      previously proposed multichannel modulation postprocessing algorithm (Chen and
      Wyrwicz, MRM 1999;41:1206-1213), the encoded phase error information can be used
      to effectively remove geometric distortions in subsequent EPI scans. The proposed
      EPI distortion correction technique has been shown to be effective in removing
      distortions due to gradient waveform imperfections and phase gradient-induced
      eddy current effects. In addition, this new method retains advantages of the
      earlier method, such as simultaneous correction of different off-resonance
      factors without use of a complicated phase unwrapping procedure. The
      effectiveness of this technique is illustrated with EPI studies on phantoms and
      animal subjects. Implementation to different versions of EPI sequences is also
      described. Magn Reson Med 45:525-528, 2001.

PMID- 11241715
TI  - T(1) and T(2) selective method for improved SNR in CSF-attenuated imaging: T(2)
      FLAIR.
AB  - We present here a method for improving SNR in CSF-attenuated imaging relative to
      the standard technique of using an inversion pulse and imaging at the null point
      of CSF. In this new method the inversion pulse is replaced with a 90(x)-180(y)
      90(x) preparation sequence that provides T(1) and T(2) selectivity. This allows
      the tissue magnetization to recover more rapidly, allows for the use of shorter
      TR values, and reduces T(1) weighting. Magn Reson Med 45:529-532, 2001.

PMID- 11241716
TI  - Relationship of psychosis to aggression, apathy and function in dementia.
AB  - BACKGROUND: Psychosis has been associated with aggression in dementia, but the
      nature of this relationship has been unclear. There has been very little research
      into the relations between apathy and functional status to psychosis in dementia.
      The purpose of this study is to investigate the relationship between psychosis
      and aggression, apathy, and functional status in outpatients with dementia.
      METHODS: The presence of psychosis was assessed by clinical interview and two
      scales: the Neuropsychiatric Inventory and the Columbia University Scale for
      Psychopathology in Alzheimer's Disease. The maximum likelihood estimation
      technique was used to determine the best estimate of the presence of psychosis.
      Aggression, apathy, and functional status (activities of daily living: ADLs) were
      measured using structured instruments. RESULTS: Sixty-one subjects were included.
      The CUSPAD and NPI provided low false positive and negative rates. ANCOVA
      analyses showed that psychosis was significantly associated with aggression, even
      when controlling for apathy, depression, and ADLs. Psychosis was related to
      apathy only when depression was controlled for. Hallucinations were related to
      impaired basic ADLs, even when depression and apathy were controlled for.
      CONCLUSIONS: Relationships were found between psychotic symptoms in dementia and
      aggression as well as apathy and impaired functional status. These relationships
      suggest pathophysiologic mechanisms and have possible treatment implications.

PMID- 11241717
TI  - Mortality and depressive symptoms in inhabitants of residential homes.
AB  - It has been hypothesised that there is a relationship between depression and
      mortality rate. Some earlier studies have confirmed this relationship, but others
      have not. In the present study the association was examined between depressive
      symptoms and mortality in the inhabitants of ten residential homes for the
      elderly in The Netherlands. Four hundred and twenty-four subjects who were not
      cognitively impaired, and who participated in an intervention study, were
      included. One year after the initial interview, they were contacted again and it
      was found that 69 (16.3%) had died. In the initial interview, depressive symptoms
      and psychological distress were assessed with the Geriatric Depression Scale and
      the mental health subscale of the MOS-SF-20. The following correlates of
      depression were assessed: functional impairment, earlier depression, pain, social
      support, loneliness, and the presence of seven common chronic illnesses. In
      bivariate analyses no significant relationship was found between depression and
      mortality, while controlling for living in an experimental or control home. In
      logistic regression analyses with mortality as the dependent variable and
      depressive symptoms, demographic variables, and correlates of depression as
      predictors, no significant relationship between depression and mortality was
      found either. It is concluded that no evidence was found in this population for a
      significant relationship between depression and mortality. Mortality was related
      to measures of social support, to activities of daily living, and to the presence
      of chronic non-specific lung disease.

PMID- 11241718
TI  - Relationship between aggressive behaviors and depression among nursing home
      residents with dementia.
AB  - BACKGROUND: Verbal and physical aggression are common behavior problems among
      nursing home residents with dementia. Depression among nursing home residents is
      also a common but underdiagnosed disorder. METHOD: Data collected on 1101
      residents with dementia, newly admitted to a sample of 59 nursing homes across
      Maryland, were analyzed to determine if there was a relationship between
      depression and physical and verbal aggression. RESULTS: Residents with dementia
      who manifested physical or verbal aggression had a higher prevalence of
      depression than those without such behaviors (p<0.05). CONCLUSIONS: Our findings
      suggest that nursing home residents with aggressive behaviors should be screened
      for depression and treated.

PMID- 11241719
TI  - Determinants for the use of psychotropics among nursing home residents.
AB  - PURPOSE: To characterise the prescription pattern of psychotropics in Danish
      nursing homes and to identify diagnostic, behavioural, cognitive and performance
      characteristics associated with prevalent psychotropic drug use. METHODS:
      Prescribed daily medication was recorded from nurses' files. Based on the
      Anatomical Therapeutical Chemical (ATC) classification index, psychotropics were
      categorised into neuroleptics, benzodiazepines and antidepressants. Two hundred
      and eighty-eight residents were diagnosed using the GMS-AGECAT. One hundred and
      eighteen staff members were interviewed about the residents's Activities of Daily
      Living (ADL), behavioural problems (Nursing Home Behavior Problem Scale),
      orientation, communication skills and if the resident had any psychiatric
      disorder. Multiple logistic regression was used to select the items that
      determined the use of psychotropics. RESULTS: Fifty-six percent of the residents
      received a psychotropic, 21% received neuroleptics, 38% received benzodiazepines
      and 24% received antidepressants. In the multivariate analysis, staff assessment
      of the resident's mental health was a determinant for the use of all types of
      specific psychotropics, whereas a GMS-AGECAT diagnosis only determined the use of
      neuroleptics. Behavioural problems were a determinant for the use of neuroleptics
      and the use of benzodiazepines irrespective of the psychiatric diagnosis of the
      resident. Use of antidepressants was associated with male gender and increasing
      age. CONCLUSIONS: Staff perceptions of psychiatric morbidity and norms have a
      greater impact on the prescription of psychotropics than standardised clinical
      criteria.

PMID- 11241720
TI  - Psychiatric disorder and personality factors associated with suicide in older
      people: a descriptive and case-control study.
AB  - OBJECTIVE: To determine the rates of psychiatric disorder and personality
      variables in a sample of older people who had committed suicide and to compare
      the rates in a subgroup of this sample with those in a control group of people
      who died from natural causes. DESIGN: Descriptive psychological autopsy study,
      including interviews with informants, of psychiatric and personality factors in
      100 suicides in older people. Case-control study using subgroup of 54 cases and
      matched control group. SETTING: Four counties and one large urban area in central
      England, UK. SUBJECTS: Individuals 60 years old and over at the time of death who
      had died between 1 January 1995 and 1 May 1998, and whose deaths had received a
      coroner's verdict of suicide (or an open or accidental verdict, where the
      circumstances of death indicated probable suicide). The control group was an age
      and sex-matched sample of people dying through natural causes in the same time
      period. MAIN OUTCOME MEASURES: ICD-10 psychiatric disorder, personality disorder
      and trait accentuation. MAIN RESULTS: Seventy-seven per cent of the suicide
      sample had a psychiatric disorder at the time of death, most often depression
      (63%). Personality disorder or personality trait accentuation was present in 44%,
      with anankastic or anxious traits the most frequent. Depression, personality
      disorder, and personality trait accentuation emerged as predictors of suicide in
      the case-control analysis. CONCLUSION: Personality factors, as well as
      depression, are important risk factors for suicide in older people.

PMID- 11241721
TI  - The Itel-MMSE: an Italian telephone version of the Mini-Mental State Examination.
AB  - METHOD: We compared performance in an Italian telephone version of the Mini
      Mental Status Examination (Itel-MMSE) with performance in the standard MMSE
      administered face to face to 104 inpatients affected by cognitive deficit.
      RESULTS: Their cognitive ability varied from mildly to severely impaired. Total
      scores of the two MMSE versions correlated strongly for all patients (r=0.85) and
      for very mildly (r=0.77), mildly (r=0.79), and moderately (r=0.72) demented. A
      weak but statistically significant correlation was observed for severely demented
      patients (r=0.46). The study establishes the validity and reliability of the Itel
      MMSE as well as between rater and test-retest reliability. We calculated a
      regression equation for use in predicting MMSE scores from Itel-MMSE scores. Data
      fit a linear regression model.

PMID- 11241723
TI  - Depression in older people with mild stroke, carotid stenosis and peripheral
      vascular disease: a comparison with healthy controls.
AB  - BACKGROUND: Although depression has a recognised association with stroke, the
      role of "silent" cerebrovascular pathology associated with carotid stenosis and
      peripheral vascular disease remains unexplored. METHODS: Four groups of 25
      community residents aged 65 and over were recruited, comprising first anterior
      circulation stroke, carotid stenosis accompanied by transient ischaemic attack,
      peripheral vascular disease and a non-vascular control group. All participants
      were interviewed using the Hamilton Rating Scale for Depression [HRSD] (including
      a modified version) and Geriatric Depression Scale. DSM IV criteria for major
      depression and measures of handicap, social support and physical illness were
      also administered. Head computerised tomography (CT) scans were performed on
      stroke patients to examine the relationship between lesion location and
      depression. RESULTS: One hundred patients were interviewed. Stroke patients were
      more likely to live in a nursing home and had less social support than other
      groups. Mean scores on the modified Hamilton and Geriatric Depression Scales were
      higher in stroke and carotid stenosis groups than controls. Patients with stroke
      did not show a higher prevalence of DSM IV major depressive disorder than those
      with carotid stenosis. There was no relationship between the presence of lesions
      affecting the frontal/subcortical system and prevalence/severity of depression.
      LIMITATIONS: Small numbers, mortality of stroke patients in hospital, possible
      selection bias in the control group and use of a previously unvalidated
      depression rating scale all limit the study. CONCLUSIONS: A possible role for
      carotid stenosis in the pathogenesis of depressive disorder is suggested. Larger
      studies incorporating brain imaging may be required to examine the mechanism of
      this association more closely. The use of a shorter version of the HRSD in older
      people with cerebrovascular disease may warrant further exploration.

PMID- 11241722
TI  - Clinical characteristics of individuals with subjective memory loss in Western
      Australia: results from a cross-sectional survey.
AB  - Subjective memory complaint is common in later life. Its relationship to future
      risk of dementia is unclear, although many reports have found a positive
      association. We designed the present cross-sectional survey to investigate the
      clinical features associated with subjective memory impairment. One hundred and
      eight volunteers and 38 non-complainers acting as age-matched controls were
      recruited. Eleven subjects with memory complaints were excluded because of prior
      stroke or low MMSE score. The CAMCOG was used to measure cognition; complainers
      had significantly lower scores (p<0.001). Univariate analysis showed that
      complainers had greater prevalence of depression, anxiety, insomnia, psychotic
      phenomenon, difficulties with ADL and word-finding difficulties. The frequency
      distribution of the apolipoprotein E epsilon4 allele was similar for both groups
      (p=0.469). Logistic regression analysis indicated that CAMCOG scores (p=0.002)
      and word-finding difficulty (p=0.002) were independently associated with memory
      complaints. These results show that memory complainers have worse cognitive
      performance than non-complainers and support the findings of other studies that
      suggest that subjective memory loss may be a reliable indicator of cognitive
      decline.

PMID- 11241724
TI  - Neuropsychiatric differences between Parkinson's disease with dementia and
      Alzheimer's disease.
AB  - OBJECTIVE: To compare the profile of neuropsychiatric symptoms in patients with
      Parkinson's disease with dementia (PDD) and patients with Alzheimer's disease
      (AD). DESIGN: Cross-sectional survey of a population-based sample of patients
      with PDD and AD patients matched for age, sex, and Mini-Mental State Examination
      (MMSE) score. METHOD: Patients were diagnosed according to published criteria for
      PD and AD. The diagnosis of dementia in PD was made according to DSM-III-R, and
      was based on clinical interview of the patient and a relative, psychometric
      testing (including MMSE, Dementia Rating Scale and tests assessing memory,
      executive functions and visuospatial functioning) and physical examination. The
      Neuropsychiatric Inventory (NPI) was administered to all patients. RESULTS: One
      or more psychiatric symptoms was reported in 95% of AD and 83% of PDD patients.
      Hallucinations were more severe in PD patients, while aberrant motor behavior,
      agitation, disinhibition, irritability, euphoria, and apathy were more severe in
      AD. In PDD, apathy was more common in mild Hoehn and Yahr stages, while delusions
      increased with more severe motor and cognitive disturbances. In PDD, only
      delusions correlated with the MMSE score. CONCLUSIONS: Neuropsychiatric symptoms
      are common and severe in patients with PDD, with important implications for the
      management of these patients. AD and PDD patients have different neuropsychiatric
      profiles, suggesting different underlying mechanisms. Cognitive impairment,
      psychopathology, and motor features progress independently in PDD patients

PMID- 11241725
TI  - Family, Alzheimer's disease and negative symptoms.
AB  - BACKGROUND: The aim of this study is to look at the correlation between the
      presence of apathy measured by Marin's scale and family complaints related to
      withdrawal and the loss of motivation, or depression. The multicentre study was
      performed on 58 non-demented elderly people, 132 outpatients with Alzheimer's
      type dementia, as well as their main caregiver. METHODS: After agreement of the
      patients and the family, the patients were assessed using different scales:
      Cornell's for depression, Marin's for apathy, MMS for cognitive disorders, and
      IRG for dependence. At the same time, two self-administered questionnaires were
      given to the patients' families: one concerning a list of complaints scored from
      1 to 4 relating to various disorders and the other addressing the boundary
      ambiguities translated from Boss' questionnaire. The 58 non-demented people were
      81.20 years old+/-13.75. One hundred and thirty-two demented patients were
      included: 39 men and 93 women. The mean age was 79.47 years+/-9.03. RESULTS: The
      first family complaint relates to the loss of motivation (65%). Apathy and
      depression occur more frequently in dementia, in particular when the MMS is
      degraded. Depression and apathy attracted a high complaint score. In our study
      the score of boundary ambiguity is higher among patients with a weak cognitive
      status. A high level of ambiguity is accompanied by a high score of family
      complaints. When the family complaint concerning the loss of motivation is
      present, apathy is significantly more common. Family complaints about withdrawal
      and loss of motivation are frequently present, and are congruent with the actual
      presence of apathy in the patient. It bears witness to the distress felt by
      families faced with the loss of ability noted in the demented person. The
      family's difficulties are increased by the patient's depression.

PMID- 11241726
TI  - Religion and end of life treatment preferences among geriatric patients.
AB  - The purpose of this study was to determine if religious preference and
      religiosity influenced choosing end of life treatments in medically ill geriatric
      patients. The sample consisted of 374 males 60 years of age or older,
      hospitalized on the acute medical service at the Baltimore Veterans Affairs
      Medical Center. Choices for end of life treatment preferences were CPR, medical
      ventilation, tube feeding and IV fluids within six different illness scenarios.
      Patients indicated how often they attended religious services, how much strength
      and comfort they got from religion and how religious they would describe
      themselves. Analyses of variance were performed using as the dependent variables
      the summation scores across the six scenarios of a willingness to undergo each of
      the four life saving procedures. The religious preference, race and religiosity
      scores served as the independent variables. Only tube feeding showed a
      significant (p<0.05) relationship, with Catholics less willing to undergo this
      procedure than other Christians. The same trend was found for the other life
      saving procedures, but was not statistically significant.

PMID- 11241727
TI  - Aggressive behaviors among demented nursing home residents in Japan.
AB  - This study investigates the frequency of aggressive behaviors in a sample of
      elderly nursing home residents with dementia in Japan. Behavioral data were
      collected on 391 residents using the Cohen-Mansfield Agitation Inventory (CMAI).
      Data were also gathered on residents' age, sex, and ability to perform self-care.
      Another scale was used to code the degree of resistance that each resident
      manifested during bathing, toileting, dressing and eating. In addition,
      qualitative data were collected from caregivers regarding their main caregiving
      problems with dementia residents. Findings show that 45.4% of the sample
      manifested aggressive behavior during the 2-week study period. Men were
      significantly more likely to manifest physically aggressive behavior, but there
      was no gender difference for verbal aggression. Age had no relationship to
      aggressive behavior. Residents who were most dependent in self-care had
      significantly higher frequencies of aggressive behaviors. Caregivers reported
      that most aggressive behavior took place during personal care. The majority of
      caregivers identified verbal agitation rather than physical aggression as their
      main caregiving problem. This study represents the first time that the CMAI has
      been translated and used in Japan and the first time empirical data has been
      collected on the behavior of dementia patients in Japanese nursing homes.

PMID- 11241728
TI  - The Mini-Cog: receiver operating characteristics with expert and naive raters.
AB  - BACKGROUND: As elderly populations grow, dementia detection in the community is
      increasingly needed. Existing screens are largely unused because of time and
      training requirements. We developed the Mini-Cog, a brief dementia screen with
      high sensitivity, specificity, and acceptability. Here we describe the
      development of its scoring algorithm, its receiver operating characteristics
      (ROC), and the generalizability of its clock drawing scoring system. SAMPLE AND
      METHODS: A total of 249 multi-lingual older adults were examined. Scores on the
      three-item recall task and the clock drawing task (CDT-CERAD version) were
      combined to create an optimal algorithm. Receiver operating characteristics for
      seven alternatives were compared with those of the MMSE and the CASI using expert
      raters. To assess the CDT scoring generalizability, 20 naive raters, without
      explicit instructions or prior CDT exposure, scored 80 randomly selected clocks
      as "normal" or "abnormal" (20 from each of four CERAD categories). RESULTS: An
      algorithm maximizing sensitivity and correct diagnosis was defined. Its ROC
      compared favorably with those of the MMSE and CASI. CDT concordance between naive
      and trained raters was >98% for normal, moderately and severely impaired clocks,
      but lower (60%) for mildly impaired clocks. Recalculation of the Mini-Cog's
      performance, assuming that naive raters would score all mildly impaired CDTs in
      the full sample as normal, retained high sensitivity (97%) and specificity (95%).
      CONCLUSION: The Mini-Cog algorithm performs well with simple clock scoring
      techniques. The results suggest that the Mini-Cog may be used successfully by
      relatively untrained raters as a first-stage dementia screen. Further research is
      needed to characterize the Mini-Cog's utility when population dementia
      prevalences are low.

PMID- 11241729
TI  - Tolerability and effectiveness of atypical antipsychotics in male geriatric
      inpatients.
AB  - The atypical antipsychotics are gradually becoming the mainstay of treatment for
      psychosis in the elderly. The present study examines the effectiveness and
      tolerability of risperidone and olanzapine treatment in 34 matched male patients
      admitted to a VA Medical Center geriatric inpatient unit. The Positive and
      Negative Syndrome Scale for Schizophrenia (PANSS), the Cohen-Mansfield Agitation
      Inventory (CMAI), the Rating Scale for Side-Effects, the Extra-Pyramidal Rating
      Scale, and the Mini-Mental State Examination were administered at admission and
      discharge. T-tests at admission and discharge across groups indicate that the
      patients as a whole were performing significantly better following their stay on
      the CMAI (t(30)=4.31, p=0.000), the GAF (t(31)=9.73, p=0.000), the PANSS total
      score (t(29)=3.82, p=0.001), and the positive symptom portion of the PANSS
      (t(28)=4.29, p=0.000). No significant differences were detected between the two
      groups with regard to length of hospitalization, or reduction in scores on the
      PANSS, or CMAI, however the daily cost of risperidone was 1/3 as much as
      olanzapine (p=0.00). The two treatments were comparable in the elderly men
      evaluated in this study.

PMID- 11241730
TI  - Failure to breathe following ECT.

PMID- 11241731
TI  - Carers' views on passive euthanasia.

PMID- 11241733
TI  - Reimbursement of acetilcholinesterase inhibitors for Alzheimer's disease in
      Europe.

PMID- 11241732
TI  - Drug induced akathisia, suicidal ideation and its treatment in the elderly.

PMID- 11241734
TI  - Alcohol problems in the elderly: a survey of psychogeriatric admissions.

PMID- 11241736
TI  - Altered outward-rectifying K(+) current reveals microglial activation induced by
      HIV-1 Tat protein.
AB  - Microglial cells are believed to be one of the key elements in the development of
      the HIV-related neuropathology. Not only can microglial cells be productively
      infected by the virus, but they are also sensitive to viral proteins. Among them,
      the HIV-1 regulatory protein Tat, which was shown to have neurotoxic activity, is
      able to promote some proinflammatory functions of microglia. Considering that
      microglial activation goes along with a change of ion channel profile, we aimed
      to study whether Tat could influence microglial electrophysiology. When
      microglial cultures obtained from neonatal rats were treated with Tat (> or = 100
      ng/ml), whole-cell recording showed the appearance of a large outwardly
      rectifying current (OR) virtually absent in untreated control cells. According to
      voltage dependence of the kinetic variables, K(+) permeability, and
      pharmacological sensitivity, the Tat-induced current was due to the presence of
      functional Kv1.3 channels. The effect of Tat was abolished by specific anti-Tat
      polyclonal antibody and by heat denaturation of Tat protein, confirming that the
      OR enhancement was due to the viral protein. Interestingly, the OR current
      induced by Tat was largely prevented by two inhibitors of the transcription
      factor NF-kappaB, TPCK and SN50, which suggests an involvement of NF-kappaB in
      the effect of the viral protein. The relatively high dose of Tat needed to
      observe an effect (> or = 100 ng/ml) might indicate that the action of Tat
      required entrance of the protein into the cell, rather than being mediated by a
      membrane receptor. In conclusion, the HIV-1 protein Tat is able to enhance OR
      K(+) current in rat microglia through a mechanism involving the activation of NF
      kappaB. We propose that such effect of Tat could be part of the process of
      microglial activation known to take place in the brain of persons with neuro
      AIDS.

PMID- 11241737
TI  - PPAR delta agonists stimulate oligodendrocyte differentiation in tissue culture.
AB  - Peroxisome proliferator-activated receptors (PPARs) are ligand-activated
      transcription factors of the nuclear hormone receptor superfamily that have been
      described as master genes that switch cells from an undifferentiated phenotype to
      a differentiated phenotype. In the present investigation, we examined the
      possibility that ligands for PPARs are potent activators of oligodendrocyte (OL)
      differentiation and/or proliferation. Primary glial cultures and enriched OL
      cultures of neonatal mouse cerebra were treated with three different PPAR
      agonists: a PPAR gamma-selective agonist, a PPAR delta-selective agonist, and a
      pan agonist selective for both PPAR gamma and delta. Treatment with PPAR gamma
      agonist does not have an effect on the differentiation of OLs; however, PPAR
      delta agonist and the pan agonist treatment accelerates the differentiation of
      OLs within 24 h of application in mixed glial cultures. The number of OLs with
      processes and huge membrane sheets increases two- to threefold in both groups.
      The increase in the size of the sheets is also mirrored by changes in the
      intensity and distribution of myelin basic protein (MBP) and proteolipid protein
      (PLP) mRNAs. As compared to controls, the PPAR delta agonist-treated groups
      contain more OLs that have MBP and PLP mRNA extending into distal processes.
      These results indicate that PPAR delta plays a significant role in the maturation
      of OLs and regulates the size of OL sheets. BrdU immunostaining reveals that
      these agonists do not significantly stimulate proliferation of OLs expressing
      glycolipids. The studies in enriched OL cultures reproduce the effects of the
      PPAR agonists seen in the mixed glial cultures, indicating that the effect of the
      PPAR agonists is directly on the OLs and not via astrocytes. In the enriched
      cultures, the total number of OLs increases significantly in the PPAR delta
      agonist-treated groups, but BrdU immunostaining does not show an increased
      proliferation of cells. These findings suggest that PPAR delta increases the
      survival of cells and/or prevents cell death in enriched cultures. Although PPAR
      delta is expressed in various cell types, its role as a factor in the
      transcriptional regulation of OL differentiation has not been explored. We show
      for the first time that a ligand that serves as an agonist for PPAR delta
      activates the program of OL differentiation in primary and enriched OL cultures.

PMID- 11241738
TI  - Expression of matrix metalloproteinases and tissue inhibitors of
      metalloproteinases in human optic nerve head astrocytes.
AB  - Glaucomatous optic neuropathy is a common blinding disease characterized by
      remodeling of the extracellular matrix (ECM) and loss of retinal ganglion cell
      (RGC) axons at the level of the optic nerve head (ONH). Astrocytes, the major
      cell type in ONH, may participate in this process by production of matrix
      metalloproteinases (MMPs) and their inhibitors (TIMPs). In normal and
      glaucomatous ONH, we detected MMP and TIMP expression by immunohistochemistry.
      Cultured astrocytes were used to characterize expression of MMPs and TIMPs by
      zymography, Western blot, and RNase protection assay. MMP production was
      stimulated with phorbol 12-myristate 13-acetate (PMA). Astrocytes expressed MMP1,
      MT1-MMP, MMP2, TIMP1, and TIMP2 in normal and glaucomatous ONH. MMP2, TIMP1, and
      TIMP2 localized to RGCs and their axons. Increased MMP1 and MT1-MMP expression
      was demonstrated in glaucoma. Cultured astrocytes constitutively expressed MMP2,
      MT1-MMP, TIMP1, and TIMP2, whereas MMP3, MMP7, MMP9, and MMP12 were not
      detectable in tissues or in cultured astrocytes. Our findings demonstrate the
      presence of specific MMPs and TIMPs in the ONH that may participate in the
      homeostasis and remodeling of the ECM in glaucoma. Expression of the same MMPs
      and TIMPs in cultured ONH astrocytes will allow further studies on the mechanisms
      regulating these enzymes.

PMID- 11241739
TI  - Caspase 8 expression and signaling in Fas injury-resistant human fetal
      astrocytes.
AB  - Fas (APO-1/CD95) is a cell surface receptor initially identified in lymphoid
      cells, but more recently detected in the central nervous system under
      pathological, usually inflammatory, conditions. In most Fas expressing cells,
      triggering of Fas by its ligand or by antagonistic antibodies leads to apoptosis.
      Human fetal astrocytes (HFA) constitutively express Fas yet are resistant to cell
      death following Fas ligation. In the current study, using dissociated cultures of
      human fetal central nervous system-derived cells, we attempted to identify a
      basis for HFA resistance to Fas-mediated injury. We compared the components of
      the Fas signaling pathway of HFA to those of two human cell lines susceptible to
      Fas-mediated injury, U251 glioma and Jurkat T-cells. We found that HFA did not
      express caspase 8 (FLICE), the caspase primarily activated on Fas signaling.
      Although we could induce caspase 8 in HFA with the inflammatory cytokines
      IFNgamma and TNFalpha, HFA remained resistant to Fas-mediated injury. Addition of
      inflammatory cytokines to the extracellular milieu also increased FLIP mRNA
      (FLICE inhibitory protein). Furthermore, upon triggering of cytokine-treated
      cells with FasL, we observed upregulation of the cleavage product of FLIP (p43
      FLIP) previously shown to associate with the DISC and to block caspase 8
      recruitment, thereby inhibiting Fas-mediated death. Our findings indicate that
      caspase 8 and its regulators play a central role in determining the response to
      Fas ligation of HFA and support a role for Fas signaling in the developing
      central nervous system other than related to cytotoxicity.

PMID- 11241740
TI  - Neurotrophic and migratory properties of an olfactory ensheathing cell line.
AB  - Olfactory ensheathing cells (OECs) are a unique type of macroglia required for
      normal olfactory axonal regeneration throughout the lifetime of an individual.
      Recent evidence in the literature suggests that OECs transplanted into injured
      spinal cords may facilitate axonal regeneration. In this study, we evaluated the
      neurotrophic properties of OECs using a homogeneous clonal cell line (nOEC),
      which does not contain contaminating cell types found in all primary OEC
      cultures. The results indicate that nOECs express mRNA for NGF, BDNF, NT-4/5, and
      neuregulins, but not for NT-3 or CNTF. In addition, nOECs secrete NGF, BDNF, and
      neuregulin, but retain NT-4/5 intracellularly. Finally, prelabeled nOECs derived
      from rat survived transplantation into a dorsal hemisected region of the hamster
      spinal cord and migrated only in the injured, dorsal portion of the spinal cord.
      This migratory pattern suggests that the nOECs are viable in vivo and respond to
      signals originating from the injured neuronal cells and their processes.

PMID- 11241741
TI  - Genetic and epigenetic control of the Na-G ion channel expression in glia.
AB  - The Na-G ion channel, previously cloned from a rat astroglia cDNA library,
      belongs to a new family of ion channels, related to but distinct from the
      predominant brain and muscle fast voltage-gated Na(+) channels. In vivo, the
      corresponding transcripts are widely expressed in peripheral nervous system
      neurons and glia, but only in selected subpopulations of neuronal and glia-like
      cells of the central nervous system. In the present report, we show that Na-G
      messenger RNA level in astrocyte and Schwann cell cultures is modulated in a cell
      specific manner by several growth factors, hormones, and intracellular second
      messengers pathways. Striking changes in transcript level were observed in the
      two types of glia in response to protein-kinase A activation and to treatment
      with the neuregulin glial growth factor, indicating regulation of the Na-G gene
      by neuroglial signaling. By transient transfection of Na-G/reporter constructs
      into cultured cells, we show that a short genomic region, encompassing the first
      exon and 375 bp upstream, bears a high glial-specific transcriptional activity
      while part of the first intron behaves as a negative regulatory element. In vivo
      footprinting experiments revealed binding of glial-specific nuclear factors to
      several sites of the Na-G promoter region. Finally, Na-G/reporter constructs are
      shown to sustain a low but reproducible transcriptional response to cAMP,
      accounting in part for the elevation in mRNA level elicited by cAMP in Schwann
      cells and its reduction in astrocytes.

PMID- 11241742
TI  - Galectin-1 is highly expressed in human gliomas with relevance for modulation of
      invasion of tumor astrocytes into the brain parenchyma.
AB  - Protein (lectin)-carbohydrate interaction is supposed to be relevant for tumor
      cell behavior. The aims of the present work are to investigate whether galectin-1
      modulates migration/invasion features in human gliomas in vitro, whether it can
      be detected in human gliomas immunohistochemically, and whether its expression is
      attributable to certain glioma subgroups with respect to invasion and prognosis.
      For this purpose, we quantitatively determined (by computer-assisted microscopy)
      the immunohistochemical expression of galectin-1 in 220 gliomas, including 151
      astrocytic, 38 oligodendroglial, and 31 ependymal tumors obtained from surgical
      resection. We also xenografted three human glioblastoma cell lines (the H4, U87,
      and U373 models) into the brains of nude mice in order to characterize the in
      vivo galectin-1 expression pattern in relation to tumor invasion of the normal
      brain parenchyma. In addition, we characterized the role in vitro of galectin-1
      in U373 tumor astrocyte migration and kinetics. Our data reveal expression of
      galectin-1 in all human glioma types with no striking differences between
      astrocytic, oligodendroglial, and ependymal tumors. The level of galectin-1
      expression correlated with the grade in the group of astrocytic tumors only.
      Furthermore, immunopositivity of high-grade astrocytic tumors from patients with
      short-term survival periods was stronger than that of tumors from patients with
      long-term survivals. In human glioblastoma xenografts, galectin-1 was
      preferentially expressed in the more invasive parts of these xenografts. In vitro
      experiments revealed that galectin-1 stimulates migration of U373 astrocytes.

PMID- 11241743
TI  - Dynamics of microglial activation: a confocal time-lapse analysis in hippocampal
      slices.
AB  - The dynamics of microglial cell activation was studied in freshly prepared rat
      brain tissue slices. Microglia became activated in the tissue slices, as
      evidenced by their conversion from a ramified to amoeboid form within several
      hours in vitro. To define better the cytoarchitectural dynamics underlying
      microglial activation, we performed direct three-dimensional time-lapse confocal
      imaging of microglial cells in live brain slices. Microglia in tissue slices were
      stained with a fluorescent lectin conjugate, FITC-IB(4), and stacks of confocal
      optical sections through the tissue were collected repeatedly at intervals of 2-5
      min for several hours at a time. Morphometric analysis of cells from time-lapse
      sequences revealed that ramified microglia progress to amoeboid macrophages
      through a stereotypical sequence of steps. First, in the withdrawal stage, the
      existing ramified branches of activating microglia do not actively extend or
      engulf other cells, but instead retract back (mean rate, 0.5-1.5 microm/min) and
      are completely resorbed into the cell body. Second, in the motility stage, a new
      set of dynamic protrusions, which can exhibit cycles of rapid extension and
      retraction (both up to 4 microm/min), abruptly emerges. Sometimes new processes
      begin to emerge even before the old branches are completely withdrawn. Third, in
      the locomotory stage, microglia begin translocating within the tissue (up to 118
      microm/h) only after the new protrusions emerge. We conclude that the rapid
      conversion of resting ramified microglia to active amoeboid macrophages is
      accomplished not by converting quiescent branches to dynamic ones, but rather by
      replacing existing branches with an entirely new set of highly motile
      protrusions. This suggests that the ramified branches of resting microglia are
      normally incapable of rapid morphological dynamics necessary for activated
      microglial function. More generally, our time-lapse observations identify changes
      in the dynamic behavior of activating microglia and thereby help define distinct
      temporal and functional stages of activation for further investigation.

PMID- 11241744
TI  - Follicular or dentigerous (tooth-containing) cyst in the premaxilla of an
      otherwise edentulous 65-year-old man.
AB  - A unilocular follicular or dentigerous cyst (FDC) with a diameter of 12 mm was
      observed incidentally in the premaxilla of a midsagittal section of the head of a
      65-year-old cadaver. The mucosal lining of the cyst was grey in color and
      granular in texture: the osseous walls had a thickness of less than 1 mm. In the
      floor of the cyst, a slender, fully developed incisor tooth was fixed in a
      horizontal position. The alveolar processes of the maxilla and mandible were
      completely edentulous. Postmortem computer tomography showed the cyst in an
      osteolytic lesion of the premaxilla, and histology revealed a lining of non
      keratinized stratified squamous epithelium supported by a lamina propria of dense
      connective tissue.

PMID- 11241745
TI  - Anatomy and clinical significance of ventricular Thebesian veins.
AB  - An injection study was carried out in sheep hearts to compare the anatomy and
      distribution of Thebesian veins (venae cordis minimae) in the ventricles. The
      left azygos, middle cardiac, small cardiac, and anterior cardiac veins were
      ligated in 36 hearts, and India ink was injected into the right coronary artery
      or the left coronary artery or the coronary sinus. Examination revealed foramina
      Thebesii in both of these cardiac chambers. Myocardial tissue samples were taken,
      and 12 were subsequently studied histologically to confirm the presence of
      Thebesian veins. A greater number of Thebesian veins were observed in the right
      ventricle than in the left (P < 0.05). To identify any larger communications
      between the coronary arteries and cardiac chambers (arterioluminal), and between
      the coronary veins and cardiac chambers (venoluminal), gelatine was injected in
      16 hearts. Arterioluminal vessels were identified only in the right ventricle,
      whereas venoluminal vessels were present in both ventricles. Venoluminal vessels
      are most likely responsible for the non-nutritive shunting of cardioplegic
      solutions delivered via the coronary sinus during surgery. Thebesian veins play a
      role in the drainage of blood, contributing towards right to left shunting of
      deoxygenated blood. It has also been suggested, although not proven, that they
      are able to supply blood to the myocardium in coronary arterial occlusion, thus
      acting as a natural form of nutrient channel. Thebesian veins may be confused
      with artificial nutrient channels constructed by transmyocardial laser
      revascularization, a possibility that should be considered during histological
      evaluation of this technique.

PMID- 11241746
TI  - Blocking the buccal nerve using two methods of inferior alveolar block injection.
AB  - The anatomic relations of the buccal nerve branch of the mandibular division of
      the trigeminal nerve were studied to explain the rationale for the discrepancy in
      blocking the buccal nerve using two methods of blocking the inferior alveolar
      nerve, the conventional method and the Gow-Gates method. The conventional method
      rarely blocks the buccal nerve, while the Gow-Gates method is reported to
      consistently block the buccal nerve. Eight head and mandibular specimens were
      dissected to observe the path of buccal nerve and its relationship to the path of
      needles in the conventional and Gow-Gates techniques. The buccal nerve descends
      on the medial and then anterior aspect of the deep head of the temporalis muscle
      (Tdh). At the latter position the buccal nerve enters the retromolar fossa and is
      encased in a fascial sleeve created by a dense fascial band that spans between
      the temporalis muscle tendons and the buccinator muscle. At the level of the
      conventional block injection the buccal nerve was shielded from the path of the
      needle by the Tdh and the fascial band. In the Gow-Gates block injection, the
      buccal nerve was exposed on the medial surface of the Tdh, immediately lateral to
      the path of the needle and proximal to the fascial sleeve. Consequently, the
      anatomical relations of the buccal nerve in the conventional block method
      essentially shield the nerve from being bathed by anesthetic solution while in
      the Gow-Gates method the relations are such that the buccal nerve can be exposed
      to anesthetic solution and thus blocked, explaining the findings in clinical
      dentistry.

PMID- 11241747
TI  - Terminologia anatomica: considered from the perspective of next-generation
      knowledge sources.
AB  - This report examines the semantic structure of Terminologia Anatomica, taking one
      page as an example. The focus of analysis is the meaning imparted to an
      anatomical term by virtue of its location within the structured list.
      Terminologia's structure, expressed through hierarchies of headings, varied
      typographical styles, indentations, and an alphanumeric code, implies specific
      relationships among the terms embedded in the list. Together, terms and
      relationships can potentially capture essential elements of anatomical knowledge.
      The analysis focuses on these knowledge elements and evaluates the consistency
      and logic in their representation. Most critical of these elements are class
      inclusion and part-whole relationships. Since these are implied, rather than
      explicitly modeled, by Terminologia, the use of the term list is limited to those
      who have some knowledge of anatomy; computer programs are excluded from
      navigating through the terminology. Assuring consistency in the explicit
      representation of anatomical relationships would facilitate adoption of
      Terminologia as the anatomical standard by the various controlled medical
      terminology (CMT) projects. These projects are motivated by the need to
      computerize the patient record, and their aim is to generate machine
      understandable representations of biomedical concepts, including anatomy. Because
      of the lack of a consistent and explicit representation of anatomy, each of these
      CMTs has generated its own anatomy model. None of these models is compatible with
      any other, yet each is consistent with textbook descriptions of anatomy. The
      analysis of the semantic structure of Terminologia Anatomica leads to some
      suggestions for enhancing the term list in ways that would facilitate its
      adoption as the standard for anatomical knowledge representation in biomedical
      informatics.

PMID- 11241748
TI  - Re-creating ancient hominid virtual endocasts by CT-scanning.
AB  - Probably the first radiographic study of human fossils, that by D. Gorganovic
      Kramberger on Neandertal remains from Krapina, Croatia, was published in 1906,
      only 11 years after Rontgen announced the discovery of X-rays. Many subsequent
      studies on fossil hominids used regular clinical diagnostic radiological
      apparatus, as depicted in Atlas of Radiographs of Early Man by M.F. Skinner and
      G.H. Sperber (1982). Some specimens such as crania filled with heavily calcified
      matrix proved intractable. Ordinary radiographs of such specimens usually failed
      to reveal endocranial structure, as fossilized bone and calcified endocast were
      approximately equally radio-opaque. Thus, neither endocranial volume nor
      structural details were detectable. The only invasive method that could have been
      employed involved mechanical removal of the solid matrix, but this entailed
      hazards to the cranial vault and the destruction of the natural endocranial cast.
      In 1983--1984, G.C. Conroy and M. Vannier utilized recent advances in high
      resolution computed tomography to produce non-invasive, intracranial capacity
      measurements of matrix-filled fossil skulls. They tried the method on two fossil
      mammal skulls filled with hard sandstone matrix (1984, Science 26:456-458), and
      then successfully applied it to a South African, matrix-filled cranium of the
      ancient hominid (hominin) species, Australopithecus africanus from Makapansgat
      (Conroy et al. 1990, Science 247:838-841). Details of the morphology of the
      endocranial surface of the braincase were revealed, including the pattern of
      venous sinus drainage in the posterior cranial fossa. A group based in St. Louis,
      Vienna, Paris, Rome, and Johannesburg has taken such studies further. Beautiful
      "virtual endocasts" have been produced on a large male specimen of A. africanus
      from Sterkfontein, South Africa, and the endocranial capacity has been determined
      (1998). The methods make it possible to re-create "virtual endocasts" of ancient
      hominids.

PMID- 11241749
TI  - Perfusion of myocardial segments of the right ventricle: role of the left
      coronary artery in infarction of the right ventricle.
AB  - In a series of 88 human hearts, from individuals aged between 24 h and 94 yr (x=
      61.09 +/- 21.96), the coronary arterial distribution of the right ventricle was
      studied using a modified Selvester's system of segmentation. Postmortem
      angiographies and microdissection techniques were used. The analysis of the six
      segments of the right ventricle shows that the three anterior segments, basal,
      mesial, and--less frequently--apical, present a type of irrigation that is
      practically constant and is dual. The postero-basal and postero-mesial segments
      are irrigated almost exclusively by the right coronary artery. In the remaining
      segments the vascularization was of mixed type, although a considerable degree of
      exclusive arterial perfusion was observed in the antero-apical segment. The
      segmental analysis allows us to conclude that although arterial vascularization
      of the right ventricle depends fundamentally on the right coronary artery, the
      anterior interventricular artery irrigates more than 20% of the right ventricular
      myocardium. Results from segmental analysis are compared with data from clinical
      and necropsic studies.

PMID- 11241750
TI  - Teaching in the dissecting room.

PMID- 11241751
TI  - Gross anatomy course content and teaching methodology in allied health:
      clinicians' experiences and recommendations.
AB  - The purpose of this study was to sample the experiences and recommendations of
      clinicians in allied health fields about gross anatomy courses. The objective was
      to determine if practicing clinicians recommended a course in gross anatomy, and,
      if so, their recommendations for course content and teaching methodology.
      Questionnaires were mailed to a random selection of occupational therapists
      (OTs), physician assistants (PAs), and physical therapists (PTs) licensed in the
      state of Texas. In addition to demographics, the survey asked 14 questions
      regarding the experiences and recommendations in seven areas of interest about
      gross anatomy courses. The responding sample appeared to be representative of the
      target population. A course in human gross anatomy during professional school was
      recommended by 96% of OTs, and 100% of PAs and PTs. The single most recommended
      teaching method was student dissection of human cadavers. Although significant
      differences were found regarding primary course orientation, a majority favored
      some form of combined systems and regional oriented courses. A majority of
      clinicians in each field recommended a gross anatomy course at the beginning of
      professional training. Specific recommendations were given for content of systems
      and regional oriented gross anatomy courses. We recommend that the gross anatomy
      course content and teaching methodologies in allied health areas be responsive to
      the specific needs of each clinical specialty.

PMID- 11241752
TI  - Evolution of embryology: a synthesis of classical, experimental, and molecular
      perspectives.
AB  - Embryology as a modern science began at the beginning of the 19th century and
      continued as the classic period until the 1940s. During this period, a body of
      basic knowledge was established which, generally, described the events of
      development. From 1940 to 1970 experimental or causal embryology predominated;
      explanations of secondary causes were demonstrated for development. The decade of
      the 1970s was a decade of transition that led to the current revolution in
      molecular biology that began in the 1980s. Molecular biology and its new branch,
      molecular genetics, shook up the heretofore serene, but already limited, field of
      embryology. Today the discipline of embryology is being built on the analysis of
      the results of genetic expression. Embryology is now concerned with understanding
      development from the viewpoint of the activation and transcription of DNA
      sequences, which will allow us to approach the first causes or underlying genetic
      and epigenetic mechanisms of development. As a result, embryology and genetics
      have fused into a wider biological subdiscipline, developmental biology. Will
      this be enough to define the full scope of our knowledge of embryonic
      development? What is certainly evident is that the molecular period of embryology
      will help achieve a better understanding of the schemata constructed by classic
      and experimental embryologists. Furthermore, to the degree that the molecular
      analysis of whatever phenomenon of development requires additional foundational
      knowledge, classic and experimental embryology will not have exhausted all their
      possibilities.

PMID- 11241754
TI  - In re: Theoretical and analytical embryology of conjoined twins, parts I and II.
      Clinical anatomy,13:36-53 and 13:97-120.

PMID- 11241755
TI  - Genetic events associated with arsenic-induced malignant transformation:
      applications of cDNA microarray technology.
AB  - Arsenic is a human carcinogen. Our recent work showed that chronic (>18 wk), low
      level (125-500 nM) arsenite exposure induces malignant transformation in normal
      rat liver cell line TRL1215. In these arsenic-transformed cells, thecellular S
      adenosylmethionine pool was depleted from arsenic metabolism, resulting in global
      DNA hypomethylation. DNA methylation status in turn may affect the expression of
      a variety of genes. This study examined the aberrant gene expression associated
      with arsenic-induced transformation with the use of Atlas Rat cDNA Expression
      microarrays. Poly(A(+)) RNA was prepared from arsenic-transformed cells and
      passage-matched control cells, and (32)P-labeled cDNA probes were synthesized
      with Clontech Rat cDNA Synthesis primers and moloney murine leukemia virus
      reverse transcriptase. The hybrid intensity was analyzed with AtlasImage software
      and normalized with the sum of the four housekeeping genes. Four hybridizations
      from separate cell preparations were performed, and mean and SEM for the
      expression of each gene were calculated for statistical analysis. Among the 588
      genes, approximately 80 genes ( approximately 13%) were aberrantly expressed.
      These included genes involved in cell-cycle regulation, signal transduction,
      stress response, apoptosis, cytokine production and growth-factor and hormone
      receptor production and various oncogenes. These initial gene expression analyses
      for the first time showed potentially important aberrant gene expression patterns
      associated with arsenic-induced malignant transformation and set the stage for
      numerous further studies. Mol. Carcinog. 30:79-87, 2001. Published 2001 Wiley
      Liss, Inc.

PMID- 11241756
TI  - Signal transduction through the Ras/Erk pathway is essential for the mycoestrogen
      zearalenone-induced cell-cycle progression in MCF-7 cells.
AB  - Zearalenone is a naturally occurring estrogenic contaminant of moldy feeds and is
      present in high concentrations in dairy products and cereals. Zearalenone was
      postulated to contribute to the overall estrogen load of women, but the
      mechanisms of its action are not known. We demonstrated that zearalenone could
      stimulate the growth of estrogen receptor-positive human breast carcinoma cell
      line MCF-7. In addition, zearalenone functioned as an antiapoptotic agent by
      increasing the survival of MCF-7 cell cultures undergoing apoptosis caused by
      serum withdrawal. Treatment of these cells with 100 nM zearalenone induced cell
      cycle transit after increases in the expression of c-myc mRNA and cyclins D1, A,
      and B1 and downregulation of p27(Kip-1). G(1)/G(2)-phase kinase activity and
      phosphorylation of the retinoblastoma gene product was also evident. Flow
      cytometric analysis demonstrated entry of cells into the S and G(2)/M phases of
      the cell cycle, and phosphorylation of histone H3 occurred 36 h after zearalenone
      treatment. Ectopic expression of a dominant-negative p21(ras) completely
      abolished the zearalenone-induced DNA synthesis in these cells, and the specific
      inhibitor PD98059 for mitogen/extracellular-regulated protein kinase kinase
      arrested S-phase entry induced by zearalenone. These data suggest that the
      mitogen-activated protein kinase signaling cascade is required for zearalenone's
      effects on cell-cycle progression in MCF-7 cells. Given the presence of this
      mycotoxin in cereals, milk, and meat, the possibility that zearalenone is a
      potential promoter of breast cancer tumorigenesis should be investigated further.
      Mol. Carcinog. 30:88-98, 2001.

PMID- 11241757
TI  - Loss of palindromic symmetry in Tg.AC mice with a nonresponder phenotype.
AB  - The Tg.AC transgenic mouse carries the v-Ha-ras oncogene under the control of the
      zeta-globin promoter and is currently being used in a short-term carcinogenesis
      assay for safety testing of pharmaceuticals. A subset of hemizygous Tg.AC mice
      was found to be nonresponsive to the tumor promoter 12-O-tetradecanoylphorbol-13
      acetate, which characteristically induces skin papillomas in these mice with
      repeated dermal applications. We previously showed that responder and
      nonresponder hemizygous Tg.AC mice carry about 40 copies of transgene but that
      the nonresponders had lost a 2-kb BamHI fragment containing the zeta-globin
      promoter sequence. The present restriction enzyme and S1 nuclease digestion
      experiments strongly suggested that the 2-kb BamHI fragment resulted from the
      orientation of two transgenes in an inverted repeat formation. Two subsets of
      nonresponder Tg.AC mice were identified. Restriction enzyme and S1 nuclease
      digestion experiments suggested that one nonresponder genotype was produced by a
      large deletion of one or more near complete copies of transgene sequence and the
      other genotype was produced by a small deletion near the apex of the "head-to
      head" juncture of the inverted repeat. Polymerase chain reaction amplification,
      cloning, and sequencing results confirmed the palindromic orientation of
      transgene in Tg.AC mice. Our results indicated that, despite the presence of
      multiple copies of transgene in a direct repeat orientation, loss of symmetry in
      the palindromic array of transgene sequence results in the loss of the responder
      phenotype in Tg.AC mice. Mol. Carcinog. 30:99-110, 2001. Published 2001 Wiley
      Liss, Inc.

PMID- 11241758
TI  - Analysis of c-Ha-ras gene mutations in skin tumors induced in carcinogenesis
      susceptible and carcinogenesis-resistant mice by different two-stage protocols or
      tumor promoter alone.
AB  - In the present study we describe the molecular analysis of c-Ha-ras gene
      mutations in 47 papillomas and 17 carcinomas developed in two lines of mice,
      carcinogenesis-susceptible (Car-S) and carcinogenesis-resistant (Car-R),
      selectively bred for extreme susceptibility or resistance to chemical skin
      carcinogenesis initiated and promoted with different doses of 7,12
      dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA).
      This study also presents the analysis of c-Ha-ras gene mutations in 22 papillomas
      and 22 carcinomas in Car-S mice initiated with DMBA and promoted with benzoyl
      peroxide (BzPo) and in seven papillomas and one carcinoma from a group of
      uniniated Car-S mice that received only BzPo treatment. The data showed that a
      A(182)-->T transversion in the c-Ha-ras gene was present in 100% and 81% of the
      skin tumors developed in Car-S and Car-R mice, respectively, after DMBA
      initiation and TPA promotion, suggesting that differences in genetic
      susceptibility can influence the frequency of c-Ha-ras mutations in the skin
      tumors produced. The same A(182)-->T mutation with an incidence of 68% was found
      in papillomas from DMBA-initiated and BzPo-promoted Car-S mice. The difference in
      the mutation frequency between DMBA/BzPo and DMBA/TPA papillomas suggested that
      the promotion step contributes to the final mutation pattern. The tumor induction
      experiment with BzPo alone showed that this compound can induce tumor development
      in 26% of Car-S mice, and the molecular analysis of the tumors showed a broad
      mutation spectrum, including mutations in codons 12, 13, and 61 of the c-Ha-ras
      gene. Mol. Carcinog. 30:111-118, 2001.

PMID- 11241759
TI  - Laminin-5-mediated gene expression in human prostate carcinoma cells.
AB  - Interactions between extracellular matrix (ECM) proteins and prostate carcinoma
      cells provide a dynamic model of prostate tumor progression. Previous work in our
      laboratory showed that laminin-5, an important member of a family of ECM
      glycoproteins expressed in the basal lamina, is lost in prostate carcinoma.
      Moreover, we showed that the receptor for laminin-5, the alpha6beta4 integrin, is
      altered in prostate tumors. However, the genes that laminin-5 potentially
      regulates and the significance of its loss of expression in prostate cancer are
      not known. We selected cDNA microarray as a comprehensive and systematic method
      for surveying and examining gene expression induced by laminin-5. To establish a
      definitive role for laminin-5 in prostate tumor progression and understand the
      significance of its loss of expression, we used a cDNA microarray containing 5289
      human genes to detect perturbations of gene expression when DU145 prostate
      carcinoma cells interacted with purified laminin-5 after 0.5, 6, and 24 h.
      Triplicate experiments showed modulations of four, 61, and 14 genes at 0.5, 6,
      and 24 h, respectively. Genes associated with signal transduction, cell adhesion,
      the cell cycle, and cell structure were identified and validated by northern blot
      analysis. Protein expression was further assessed by immunohistochemistry. Mol.
      Carcinog. 30:119-129, 2001.

PMID- 11241760
TI  - Ultra-fast gradient vs. fast isocratic chromatography in bioanalytical
      quantification by liquid chromatography/tandem mass spectrometry.
AB  - Liquid chromatography/tandem mass spectrometry (LC/MS/MS) methods developed for
      quantification using rapid ('ballistic') gradients on narrow bore, short HPLC
      columns have been previously described by this laboratory. This paper compares
      the fast gradient approach with the more traditional high-organic isocratic
      LC/MS/MS methods. The comparison is based on an analysis of the effectiveness of
      the chromatographic separations when using the two approaches (i.e. k', N, and
      W). The data presented herein are derived from actual biological samples analyzed
      as part of the drug discovery process.

PMID- 11241761
TI  - Self-association of an amphipathic helix peptide inhibitor of HIV-1 integrase
      assessed by electro spray ionization mass spectrometry in trifluoroethanol/water
      mixtures.
AB  - Establishing the auto-associative properties of a molecule in solution can be
      important for determination of its structure and function. EAA26
      (VESMNEELKKIIAQVRAQAEHLKTAY) has been designed to inhibit HIV-1 integrase via
      formation of a stable coiled-coil structure with a nearly homologous segment in
      the enzyme. The latter catalyzes the permanent incorporation of a DNA copy of the
      retrovirus genome into host cell DNA, and is thus essential to the life of the
      retrovirus. This makes integrase an obvious drug target in the therapy of AIDS.
      The present work has demonstrated, using electrospray ionization mass
      spectrometry (ESI-MS), that EAA26 is monomeric in pure water, and tetrameric and
      dimeric at respectively low and medium concentrations of 2,2,2-trifluoroethanol
      (TFE), and again monomeric at higher TFE concentrations. Thus, the apolar solvent
      TFE may contribute to either stabilization or disruption of the intermolecular
      hydrophobic contacts depending on its concentration in aqueous solution. Previous
      NMR and ultracentifugation results are thus confirmed, indicating the reliability
      of ESI-MS for defining the self-association state of biologically relevant
      peptides in both water and organic-water solutions.

PMID- 11241762
TI  - Liquid chromatography ion trap mass spectrometric analysis of oligosaccharides
      using permethylated derivatives.
AB  - Reversed phase liquid chromatography was combined with the multiple stage mass
      analysis capability of an ion trap mass spectrometer for the characterization of
      permethylated oligosaccharide mixtures. The new method was used to separate the
      components of an unlabeled permethylated maltooligomer ladder, a 2-aminobenzamide
      labeled (2-AB) maltooligomer ladder, a complex mixture of 2AB-labeled bi- (B),
      tri- (T), and tetraantennary (Q) standards, and a mixture of recombinant
      glycoprotein carbohydrates from soluble CD4 with varying sialic acid (S) content.
      Using reversed phase HPLC, permethylated mixture components including alpha and
      beta anomers were separated based on their structures. Fluorescent labeling with
      2-aminobenzamide prior to permethylation was employed for off-line method
      development, but was not necessarily required for mass spectral analysis, as
      permethylation alone improved the ionization and fragmentation characteristics of
      the molecules. Antennae composition of permethylated derivatives was determined
      in MS(2) where the fragmentation patterns of the Y- and B-ion series
      predominated, and then further evaluated in MS(3), which provided additional
      information on branching obtained from A and X cross-ring fragmentation.

PMID- 11241763
TI  - Cassette-accelerated rapid rat screen: a systematic procedure for the dosing and
      liquid chromatography/atmospheric pressure ionization tandem mass spectrometric
      analysis of new chemical entities as part of new drug discovery.
AB  - This report addresses the continuing need for increased throughput in the
      evaluation of new chemical entities (NCEs) in terms of their pharmacokinetic (PK)
      parameters by describing an alternative procedure for increasing the throughput
      of the in vivo screening of NCEs in the oral rat PK model. The new approach is
      called "cassette-accelerated rapid rat screen" (CARRS). In this assay, NCEs are
      dosed individually (n = 2 rats/compound) in batches of six compounds per set. The
      assay makes use of a semi-automated protein precipitation procedure for sample
      preparation in a 96-well plate format. The liquid chromatography/atmospheric
      pressure ionization tandem mass spectrometry (LC/API-MS/MS) assay is also
      streamlined by analyzing the samples as "cassettes of six". Using this new
      approach, a threefold increase in throughput was achieved over the previously
      reported "rapid rat screen".

PMID- 11241764
TI  - High-resolution analysis of a 144-membered pyrazole library from combinatorial
      solid phase synthesis by using electrospray ionisation Fourier transform ion
      cyclotron resonance mass spectrometry.
AB  - A compound library consisting of 144 pyrazole carboxylic acids and six
      sublibraries consisting of 24 components was analysed using electrospray
      ionisation Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR
      MS). The library was synthesised by the split-mix method and investigated by
      direct infusion analysis by which 134 compounds were detected. FTICR-MS is
      predestined for the direct characterisation of complex compound libraries because
      of its outstanding mass resolution and mass accuracy. However, discrimination
      within the electrospray ionisation process sometimes leads to signal suppression
      and thus to misinterpretation of the synthetic results. Using micro-HPLC/MS we
      were able to assign all 144 compounds including all pairs of isobaric pyrazoles.
      We also show that, due to partial separation, FTICR-MS is indispensable for
      proper detection of co-eluting compounds.

PMID- 11241765
TI  - Genotyping short tandem repeats using flow injection and electrospray ionization
      Fourier transform ion cyclotron resonance mass spectrometry.
AB  - Characterizing polymerase chain reaction (PCR) amplicons has been accomplished
      for the first time using flow injection analysis coupled to electrospray
      ionization mass spectrometry (ESI-MS). The PCR amplicons were amplified at the
      human tyrosine hydroxylase short tandem repeat locus from an individual
      homozygotic for the 9.3 allele. One product was amplified using Pfu polymerase
      and yielded a blunt-ended amplicon of 82 base-pairs (bp) in length. The second
      PCR product was amplified using Taq polymerase that resulted in an amplicon with
      cohesive termini of 82 bp plus either mono- or diadenylation. The two PCR
      amplicons were alternatively injected using a 0.5-microL loop at 2 microM for the
      Pfu amplicon and 1 microM for the Taq amplicon with a flow rate of 200 nL/min
      during data acquisition. Both PCR amplicons were accurately identified using mass
      measurements illustrating the compatibility of ESI-MS for genotyping short tandem
      repeat sequences and the potential for high-throughput genotyping of large PCR
      amplicons.

PMID- 11241766
TI  - Evaluation of protein modification during anti-viral heat bioprocessing by
      electrospray ionization mass spectrometry.
AB  - During the preparation of therapeutic plasma and recombinant protein
      biopharmaceuticals heat-treatment is routinely applied as a means of viral
      inactivation. However, as most proteins denature and aggregate under heat stress,
      it is necessary to add thermostabilizing excipients to protein formulations
      destined for anti-viral heat-treatment in order to prevent protein damage. Anti
      viral heat-treatment bioprocessing therefore requires that a balance be found
      between the bioprocessing conditions, virus kill and protein integrity. In this
      study we have utilized a simple model protein, beta-lactoglobulin, to investigate
      the relationship between virucidal heat-treatment conditions (protein formulation
      and temperature) and the type and extent of protein modification in the liquid
      state. A variety of industrially relevant heat-treatments were undertaken, using
      formulations that included sucrose as a thermostabilizing excipient. Using liquid
      chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) we show here
      that protein modifications do occur with increasingly harsh heat-treatment. The
      predominant modification under these conditions was protein glycation by either
      glucose or fructose derived from hydrolyzed sucrose. Advanced glycation end
      products and additional unidentified products were also present in beta
      lactoglobulin protein samples subjected to extended heat-treatment. These
      findings have implications for the improvement of anti-viral heat-treatment
      bioprocesses to ensure the safety and efficacy of protein biopharmaceuticals.
      CopyrightCopyright 2001 John Wiley & Sons, Ltd.

PMID- 11241767
TI  - Continuous flow stable isotope methods for study of delta(13)C fractionation
      during halomethane production and degradation.
AB  - Gas chromatography/mass spectrometry/isotope ratio mass spectrometry (GC/MS/IRMS)
      methods for delta(13)C measurement of the halomethanes CH(3)Cl, CH(3)Br, CH(3)I
      and methanethiol (CH(3)SH) during studies of their biological production,
      biological degradation, and abiotic reactions are presented. Optimisation of gas
      chromatographic parameters allowed the identification and quantification of
      CO(2), O(2), CH(3)Cl, CH(3)Br, CH(3)I and CH(3)SH from a single sample, and also
      the concurrent measurement of delta(13)C for each of the halomethanes and
      methanethiol. Precision of delta(13)C measurements for halomethane standards
      decreased (+/-0.3, +/-0.5 and +/-1.3 per thousand) with increasing mass (CH(3)Cl,
      CH(3)Br, CH(3)I, respectively). Given that carbon isotope effects during
      biological production, biological degradation and some chemical (abiotic)
      reactions can be as much as 100 per thousand, stable isotope analysis offers a
      precise method to study the global sources and sinks of these halogenated
      compounds that are of considerable importance to our understanding of
      stratospheric ozone destruction.

PMID- 11241768
TI  - Monitoring the production yields of vincristine and vinblastine in Catharanthus
      roseus from somatic embryogenesis. Semiquantitative determination by flow
      injection electrospray ionization mass spectrometry.
AB  - A semiquantitative determination of two bis-indole antitumor alkaloids,
      vincristine and vinblastine, has been performed by flow-injection electrospray
      ionization mass spectrometric analysis of the extracts of Catharanthus roseus.
      Leaves and flowers of two different phenotypes (pink flower and white flower)
      obtained from somatic embryogenesis were thus examined and compared with the
      field-grown mother plant. Different amounts of vincristine and vinblastine were
      detected depending on the examined samples.

PMID- 11241769
TI  - Influence of constituent mass on secondary ion yield enhancements from polyatomic
      ion impacts on aminoethanethiol self-assembled monolayer surfaces.

PMID- 11241770
TI  - Transition nuclear proteins during spermiogenesis: unrepaired DNA breaks not
      allowed.
AB  - The completion of spermiogenesis requires condensation of the haploid spermatid
      genome. This task is accomplished in a gradual and relentless manner by first
      erasing the nucleosomal organization of chromatin while the DNA is protected by
      transient nuclear proteins TP1 and TP2. Then, the more permanent protamines come
      into play to stabilize the spermatid genome until fertilization occurs. Mice
      lacking TPI manage to produce relatively structurally normal sperm, although
      fertility is reduced and chromatin condensation is abnormal despite the
      compensatory expression of TP2. TP1 and TP2 appear to have the house-keeping
      function of reestablishing continuity when chromatin breaks take place during the
      remodeling process. DNA single-strand breaks are frequently observed when
      spermiogenesis is half completed. There is a temporal relationship between TP1
      and DNA breaks: TP1 nuclear levels increase and the frequency of DNA breaks
      become less prominent as spermiogenesis is reaching completion. TP1 seems to hold
      the broken ends together until an as-yet-unidentified ligase bridges the gap.

PMID- 11241771
TI  - Expression and localisation of thioredoxin in mouse reproductive tissues during
      the oestrous cycle.
AB  - Thioredoxin expression within the reproductive tissues of the female mouse was
      analysed during the oestrous cycle stages of dioestrus, oestrus and metoestrus by
      Western blot analyses and immunocytochemistry. From Western blot analyses the
      expression of thioredoxin was found to be increased in oestrus compared to
      dioestrus and metoestrus. Localisation of thioredoxin within the reproductive
      organs of the mouse during the oestrous cycle has shown that the expression of
      thioredoxin is specific for distinct areas within the reproductive organs. These
      areas are the stratified squamous epithelium of the vagina, the simple columnar
      epithelium and the uterine glands of the uterus, the ciliated columnar epithelium
      of the oviduct, the corpus lutea, the interstitial cells and the secondary
      follicles of the ovary. The discrete cellular localisation and oestrous
      dependence of thioredoxin expression are suggestive of specific roles in various
      reproductive processes.

PMID- 11241772
TI  - Rat transition nuclear protein 2 regulatory region directs haploid expression of
      reporter gene in male germ cells of transgenic mice.
AB  - During spermiogenesis, the successive replacement of somatic histones by basic
      proteins, the transition nuclear proteins and protamines, allows normal sperm
      condensation. Transition nuclear protein 2 (TNP2) is transcribed postmeiotically
      in round spermatids. In order to determine regulatory flanking sequences
      responsible for stage specific expression of TNP2 gene, different transgenic mice
      were generated by microinjection of fertilized eggs. We demonstrate here that 525
      bp of 5'- and 920 bp of 3'-flanking sequences of rat TNP2 gene could properly and
      efficiently direct chloramphenicol acetyltransferase gene expression to the
      postmeiotic male germ cells of transgenic mice. During male germ cell
      differentiation the first transgene transcripts were observed in round spermatids
      and translation started 6 days later in elongating spermatids, which is an
      evidence for posttranscriptional regulation of transgene expression. In contrast,
      transgenic mice bearing only the 525 bp 5'-flanking sequences of rat transition
      protein 2 gene and 3'-flanking sequences of the simian virus 40 large T antigen
      showed low levels of transgene expression in testis. From these results, it can
      be concluded that the 525 bp 5'-flanking sequences regulate the cell specific
      expression and the sequences located in 920 bp 3'-flanking region either enhance
      the transgene expression in the male germ cells or may have a posttranscriptional
      role in stabilizing the mRNA in addition to its function in delaying the mRNA
      translation. Using comparative alignment of 5'-flanking of TNP2 genes from
      different species, the putative regulatory sequences are identified.

PMID- 11241773
TI  - Mouse cloning with nucleus donor cells of different age and type.
AB  - We have tested different cell types as sources for nucleus donors to determine
      differences in cloning efficiency. When donor nuclei were isolated from cumulus
      cells and injected into recipient oocytes from adult hybrid mice (B6D2F1 and
      B6C3F1), the success rate of cloning was 1.5-1.9%. When cumulus cell donor nuclei
      were isolated from adult inbred mice (C57BL/6, C3H/He, DBA/2, 129/SvJ, and
      129/SvEvTac), reconstructed oocytes did not develop to full term or resulted in a
      very low success rate (0-0.3%) with the exception of 129 strains which yielded
      0.7-1.4% live young. When fetal (13.5-15.5 dpc), ovarian, and testicular cells
      were used as nucleus donors, 2.2 and 1.0% of reconstructed oocytes developed into
      live offspring, respectively. When various types of adult somatic cells
      (fibroblasts, thymocytes, spleen cells, and macrophages) were used, oocytes
      receiving thymocyte nuclei never developed beyond implantation, whereas those
      receiving the nuclei of other cell types did. These results indicate that adult
      somatic cells are not necessarily inferior to younger cells (fetal and ES cells)
      in the context of mouse cloning. Although fetal cells are believed to have less
      genetic damage than adult somatic cells, the success rate of cloning using any
      cell types were very low. This may largely be due to technical problems and/or
      problems of genomic reprogramming by oocytes rather than the accumulation of
      mutational damage in adult somatic cells.

PMID- 11241774
TI  - Development of bovine embryo-derived clones after increasing rounds of nuclear
      recycling.
AB  - This study assessed in vitro and in vivo developmental ability of bovine embryo
      derived clones after one, four or seven rounds of nuclear transfer. Initial donor
      embryo production and all subsequent cultures were performed in vitro. Donor
      clonal embryo lines were vitrified and warmed either once (first generation),
      twice (third generation) or three times (sixth generation) before the final round
      of cloning. No differences were observed in fusion, cleavage and development
      rates to the 16-cell stage between the first six cloning generations. Likewise,
      neither the fusion nor cleavage rates were different between first, fourth and
      seventh generation clones. However, development to morulae and blastocysts
      decreased significantly as the number of recycling rounds increased (24.8, 15.1
      and 13.6% for first, fourth and seventh generation, respectively). In addition,
      the proportion of blastocysts compared to morulae decreased, indicating slower
      developmental speed in later generation clones. After transfer of 16, 25 and 7
      clones to 7, 11 and 2 recipients (first, fourth and seventh generation,
      respectively) initial pregnancy rates of 57, 27 and 0% were obtained. Final rates
      of calves to term were 25 and 4% per transferred clone for first and fourth
      generation clones, respectively. These results indicate greatly reduced in vitro
      and in vivo developmental capacity of bovine embryo-derived clones after several
      rounds of nuclear recycling. Whether it is caused by intrinsic factors associated
      with the genome modification and reprogramming as such, or by external factors
      such as prolonged in vitro culture period or the effects of vitrification,
      remains to be determined.

PMID- 11241775
TI  - Control of interferon-tau secretion by in vitro-derived bovine blastocysts during
      extended culture and outgrowth formation.
AB  - A series of experiments was conducted to examine the pattern of interferon-tau
      (IFN-tau) secretion by bovine blastocysts during extended culture in vitro. In
      the first experiment, blastocysts were cultured individually for three 48-hour
      periods. The day of blastocyst formation affected how much IFN-tau was produced
      during the first two culture periods, but not during the third period. The
      overall secretion of IFN-tau during the 6-day period increased significantly and
      well beyond what could be accounted for by the concomitant increase in cell
      numbers. In the second experiment, blastocysts were initially cultured in
      individual droplets for 48 hr, then plated into 48-well plates. Medium
      concentrations of IFN-tau were determined after 48 hr and again after 6 and 12
      days of culture. Initial IFN-tau secretion did not affect the ability to form
      outgrowths or their final size, and initial differences in secretion between
      groups of blastocysts had disappeared by the second and third analyses. In the
      third experiment, blastocysts were cultured individually for 48 hr in droplets
      containing the medium that had been flushed through the uteri of non-pregnant
      sheep on days 10, 12, and 15 of the estrous cycle. Culture in the medium obtained
      from the Day 15 flush significantly increased the number of cells that
      blastocysts contained, as well as IFN-tau secretion.

PMID- 11241776
TI  - Expression and regulation of H+K+ATPase in lysosomes of epithelial cells of the
      adult rat epididymis.
AB  - Endocytosis is an important event in the epididymis as it contributes to a
      luminal environment conducive for sperm maturation. Principal and clear cells
      contain numerous lysosomes which degrade many substances internalized by
      endocytosis from the epididymal lumen. The interior of the lysosomes depends on
      low pH to activate the release of their enzymes and to activate their acid
      hydrolases. In the present study, H+K+ATPase was localized by light microscopy in
      the adult rat epididymis of intact and of orchidectomized animals supplemented
      with testosterone or not. In normal animals, numerous lysosomes of nonciliated
      cells of the efferent ducts were intensely reactive for anti-H+K+ATPase antibody.
      In the initial segment, only a few lysosomes of principal cells were reactive. In
      the intermediate zone of the epididymis, numerous lysosomes of principal cells
      were intensely reactive, while the number of intensely reactive lysosomes
      decreased progressively from the proximal caput to the distal caput with none
      being seen in the proximal corpus region. In the distal corpus and cauda regions,
      only a few lysosomes of some principal cells were reactive. In contrast, clear
      cells of all regions showed intense reactivity. Orchidectomy resulted in the
      abolishion of H+K+ATPase in lysosomes of principal cells of all regions except
      the initial segment. However, while clear cells of the caput and corpus regions
      also became unreactive, those of the cauda region remained as reactive as in
      controls. Orchidectomized animals supplemented with testosterone maintained a
      staining pattern similar to controls for both cell types. These observations
      demonstrate the presence in principal and clear cells of H+K+ ATPase which may
      have an important role in acidifying the interior of their lysosomes. However,
      there is a region-specific expression of H+K+ATPase in lysosomes of principal
      cells, unlike that for clear cells. In addition, H+K+ATPase expression in
      lysosomes of principal cells depends on testosterone in all regions except the
      initial segment. However, in the case of clear cells, only those of the caput and
      the corpus regions are dependent on testosterone, while those of the cauda region
      appear to be regulated by some other factor.

PMID- 11241777
TI  - In vitro reproductive toxicity of polychlorinated biphenyls: effects on oocyte
      maturation and developmental competence in cattle.
AB  - Polychlorinated biphenyls (PCBs) are one of the most persistent and widespread
      group of endocrine disrupting compounds in the ecosystem. High concentrations of
      these substances are known to be present in sewage sludge from industrial,
      agricultural, and domestic origin that is spread in increasing amounts on arable
      land and pasture as fertilizer and is found in water, representing an increasing
      risk for the reproductive health of farm animals. Objective of this study was to
      determine the impact of PCBs on maturation and developmental competence of cattle
      oocytes. Since PCBs are a family of 209 molecules present in the environment as a
      mixture, Aroclor-1254, a pool of more than 60 congeners, was used in these
      experiments as its composition is considered to be environmentally relevant.
      Cumulus-oocytes complexes were exposed during IVM to serial concentrations of
      Aroclor-1254 (between 1 microg/ml and 0.0001 microg/ml) and compared with control
      groups. Aroclor decreased the percentage of oocytes that reached metaphase II
      stage after 24 hr, at doses as low as 0.01 microg/ml. Groups treated with 0.001
      microg/ml or above, showed an impaired fertilization rate and a dramatic increase
      of polyspermy. Moreover, exposure during maturation resulted in a reduced
      proportion of oocytes that cleaved and developed until blastocyst stage although
      no differences in embryo cell numbers were observed. The present study indicates
      that very low PCBs concentrations are sufficient to disrupt bovine oocyte
      maturation, its fertilization, and developmental competence. These results also
      provide a set of reference data for the assessment of the risk posed by these
      substances to animal reproductive health, though further work will be necessary
      to equate in vitro doses to in vivo exposures.

PMID- 11241778
TI  - Estrogenic upregulation of DNA polymerase beta in oocytes of preovulatory ovine
      follicles.
AB  - The basic premise of this investigation was that local hormonal control of
      stockpiling of the base excision repair polymerase (poly) beta within oocytes of
      preovulatory follicles occurs as a function of cytoplasmic maturation. There was
      an increase in immunoreactive poly beta in sectioned oocytes of preovulatory
      ovine follicles during a 12-36-hour interval following the onset of prostaglandin
      (PG) F2alpha-induced (Day 14 of the estrous cycle) luteal regression; this
      response was not observed in subordinate (nonovulatory) follicles. Accumulation
      of poly beta in oocytes at 36 hr after PGF2alpha was negated by treatment of ewes
      at 12 hr with the aromatase inhibitor Arimidex or an ovulatory dose of GnRH
      (which, via surge gonadotropin stimulation, acutely downregulates the proestrous
      rise in follicular estrogen biosynthesis). Estradiol-17beta stimulated poly beta
      expression (transcriptional control) in oocytes of explanted (12 hr after
      PGF2alpha) follicles (24-hour incubation). We suggest that a critical period of
      estrogen amplification in the preovulatory follicle underscores the capacity of
      its oocyte to efficiently repair DNA and therefore reconcile spontaneous
      infidelities in genomic integrity that inevitably occur during preimplantation
      embryogenesis.

PMID- 11241779
TI  - Regulation of in vitro penetration of frozen-thawed boar spermatozoa by caffeine
      and adenosine.
AB  - Effects of caffeine and adenosine on the function and in vitro penetration of
      frozen-thawed boar spermatozoa were examined. First, the effect on sperm function
      was determined by the chlortetracycline fluorescence assessment. Both caffeine
      and adenosine stimulated capacitation of spermatozoa. However, adenosine, but not
      caffeine, inhibited spontaneous acrosome loss. Second, sperm penetration into in
      vitro matured oocytes was compared among spermatozoa cultured in the absence or
      presence of caffeine or adenosine. Both caffeine and adenosine increased the
      penetration rate (99.1 +/- 0.9% in caffeine, 72.4 +/- 2.0% in adenosine vs. 54.8
      +/- 5.1% in controls) but only caffeine decreased drastically the monospermic
      penetration rate (8.0 +/- 2.3% in caffeine vs. 75.4 +/- 4.8% in adenosine and
      78.6 +/- 4.8% in controls). When oocytes were cocultured in various sperm
      concentrations, the proportion of monospermy changed in inverse proportion to
      sperm concentration in the presence of caffeine, but did not change in the
      presence of adenosine. A relatively high number of spermatozoa at the early stage
      of spontaneous acrosome reaction in the presence of caffeine may be one of the
      main causes of polyspermic penetration in porcine IVF system. These results
      indicate that replacement of caffeine with adenosine in fertilization medium
      improves monospermic penetration by frozen-thawed boar spermatozoa.

PMID- 11241780
TI  - Sucrose pretreatment for enucleation: an efficient and non-damage method for
      removing the spindle of the mouse MII oocyte.
AB  - Oocytes enucleated at metaphase II stage can support reprogramming of transferred
      nucleus and further developing to term. However, the first polar body in mice
      sometimes migrates away from the original place of expulsion, so the chromosomes
      of the oocyte will displace from the first polar body. Thus, it is not always
      possible to successfully enucleate according to the position of the first polar
      body. Here we use sucrose treatment to visualize metaphase spindle fibers and
      chromosomes with standard light microscopy. In the manipulation medium containing
      3% sucrose, oocytes of poor quality become shrunken, deformed or fragmented,
      while oocytes of good quality in the same medium would show a swelling around the
      metaphase chromosomes and a transparent spindle area, shaped like "infinity" and
      "0". So it is easy to remove the well-distinguished spindle and chromosomes in
      oocytes of good quality. Re-examined by Hoechst 33342 stain under the UV light,
      the enucleation rate was 100%. There was no significant difference in IVF and
      cleavage rates between the sucrose treatment and the control group. In
      conclusion, this study demonstrated that 3% sucrose pretreatment can give a
      method for evaluating embryo quality and more importantly, it can, under a common
      microscope, allow the visualization of the spindle and chromosomes in oocytes of
      good quality and hence efficiently improve enucleation rate without any harm.

PMID- 11241781
TI  - Stimulation of DNA repair by the spermatidal TP1 protein.
AB  - The chromatin remodeling process that takes place during spermiogenesis in
      mammals is characterized by a transient increase in DNA single-strand breaks
      (SSB). The mammalian transition proteins (TPs) are expressed at a high level at
      mid-spermiogenesis steps coincident with chromatin remodeling and could be
      involved in the repair of these lesions since SSB are no longer detected in
      terminally differentiated spermatids. We report that TP1 can stimulate the repair
      of SSB in vitro and demonstrate that in vivo repair of UV-induced DNA lesions is
      enhanced in mammalian cells stably expressing TP1. These results suggest that,
      aside from its role in DNA compaction, this major transition protein may
      contribute to the yet unidentified enzymatic activity responsible for the repair
      of SSB at mid-spermiogenesis steps. These results also suggest that the TP1
      proteins have the potential to participate in the repair process following
      genotoxic insults and therefore may play an active role in the maintenance of the
      integrity of the male haploid genome during spermiogenesis.

PMID- 11241782
TI  - Control of oocyte recruitment: regulative role of follicle cells through the
      release of a diffusible factor.
AB  - To determine whether oogonial proliferation and oocyte recruitment are under
      control of hypophyseal and/or ovarian factors, we carried out a series of
      investigations using Podarcis sicula, a lizard inhabiting the temperate lowlands
      of Europe in which oocyte recruitment occurs throughout the year, as animal
      model. Germinal beds containing oogonia and oocytes in prefollicular stages were
      cocultured with different ovarian compartments in presence/absence of FSH, and
      the effects of different treatments were evaluated by counting the number of
      prelepto-leptotene oocytes. Results revealed that oocyte recruitment from the
      pool of oogonia is under the control of a factor released by follicle cells while
      FSH has an indirect effect on modulating oogonial proliferation. SDS-PAGE
      analyses carried out on media conditioned by follicles suggest that the factor
      involved in the control of oocyte recruitment may be a small protein (about 21
      kDa) and that its release is dependent on the period of the ovarian cycle but
      apparently not on the circulating levels of FSH.

PMID- 11241783
TI  - Induction of the acrosome reaction in dog sperm cells is dependent on epididymal
      maturation: the generation of a functional progesterone receptor is involved.
AB  - In the current study we investigated the progesterone receptor exposure on the
      sperm from the testis and different parts of the epididymis, the relation to the
      sperm maturation stage, the functionality of the progesterone receptor and the
      capacity of sperm to undergo acrosome reaction. Exposed progesterone receptors on
      spermatozoa were detected using Progesterone-BSA conjugate labeled with
      fluorescein isothiocyanate (P-BSA-FITC) or a monoclonal antibody against
      progesterone receptor, C-262. Either progesterone or calcium ionophore was used
      to induce acrosome reaction. A high percentage (69 +/- 8%; mean +/- SD) of
      spermatozoa from the cauda epididymis showed P-BSA-FITC labeling at the onset of
      incubation, whereas only 0.1 +/- 1 and 4 +/- 2%, of spermatozoa from the testes,
      caput, and corpus epididymis, respectively, were labeled. There was no
      significant increase in P-BSA-FITC binding during the course of a 6 hr
      incubation. Treatment with either 10 microM progesterone or 5 microM calcium
      ionophore induced acrosome reaction in cauda epididymal sperm but not in
      testicular sperm, caput or corpus epipidymal sperm. It is concluded that the
      matured sperm of the dog from cauda epididymis and freshly ejaculated sperm
      demonstrate a functional membrane-bound progesterone receptor while less matured
      spermatozoa from the testicle, caput, and corpus epididymis fail to demonstrate
      such a receptor. Acrosome reaction of dog sperm can be induced using either
      progesterone or calcium ionophore; however, the maturation stages of spermatozoa
      influence this occurrence.

PMID- 11241785
TI  - Intrinsic genetic instability of normal human lymphocytes and its implication for
      loss of heterozygosity.
AB  - A combination of flow cytometry and microsatellite analysis was used to
      investigate loss of expression of HLA-A and/or HLA-B alleles and concurrent LOH
      at polymorphic chromosome 6 loci both in freshly isolated lymphocytes (in vivo
      mutations) and in lymphocytes cultured ex vivo. The fraction of in vivo mutants
      that showed LOH at 6p appeared to vary from 0%-49% for various donors. During
      culturing ex vivo, HLA-A(-) cells arose at a high rate and showed simultaneous
      loss of expression at the linked HLA-B locus. Up to 90% of the ex vivo arisen HLA
      A2(-) cell population showed LOH of multiple 6p markers, and 50% had lost
      heterozygosity at 6q. This ex vivo spectrum resembles that found in HLA-A2
      mutants obtained from lymphoblastoid cells. The HLA-A2 mutants present in vivo
      may reflect only a small fraction of the mutants that can be detected ex vivo. In
      normal lymphocytes, in vivo only mitotic recombination appears to be sustained,
      indicating the importance of this mechanism for tumor initiation in normal cells.
      Although mutations resulting in LOH at both chromosome 6 arms were shown to
      result in nonviable cells in normal lymphocytes, they have been shown to result
      in viable mutants in lymphoblastoid cells. We hypothesize that these types of
      mutations also occur in vivo but only survive in cells that already harbor a
      mutated genetic background. In light of the high rate at which these types of
      mutations occur, they may contribute to cancer progression.

PMID- 11241784
TI  - Elevated levels of the polyadenylation factor CstF 64 enhance formation of the
      1kB Testis brain RNA-binding protein (TB-RBP) mRNA in male germ cells.
AB  - The single copy mouse Testis Brain RNA-Binding Protein (TB-RBP) gene encodes
      three mRNAs of 3.0, 1.7, and 1.0 kb which only differ in their 3' UTRs. The 1 kb
      TB-RBP mRNA predominates in testis, while somatic cells preferentially express
      the 3.0 kb TB-RBP mRNA. Here we show that the 1 kb mRNA is translated several
      fold more efficiently than the 3 kb TB-RBP in rabbit reticulocyte lysates and
      cells with elevated levels of the 1 kB TB-RBP mRNA express high levels of TB-RBP.
      To determine if the cleavage stimulatory factor CstF 64 can modulate the
      alternative splicing of the TB-RBP pre-mRNA and therefore TB-RBP expression, CstF
      64 levels and binding to alternative polyadenylation sites were examined. CstF 64
      is abundant in the testis and preferentially binds to a distal site in the TB-RBP
      pre-mRNA that produces the 3 kb TB-RBP. Moreover, upregulation or overexpression
      of CstF 64 increases the poly(A) site selection for the 1 kb TB-RBP mRNA. We
      propose that the level of the polyadenylation factor CstF 64 modulates the level
      of TB-RBP synthesis in male germ cells by an alternative processing of the TB-RBP
      pre-mRNA.

PMID- 11241786
TI  - TCL1 is activated by chromosomal rearrangement or by hypomethylation.
AB  - TCL1 is an oncogene activated by recurrent reciprocal translocations at
      chromosome segment 14q32.1 in the most common of the mature T-cell malignancies,
      T-cell prolymphocytic leukemia. It acts to transport Akt1 to the nucleus and
      enhance Akt1's serine-threonine kinase activity. TCL1 is also expressed in the B
      cell malignancy, Burkitt's lymphoma (BL). However, 14q32.1 breakpoints have not
      been detected in BL, and we therefore investigated in more detail how expression
      was activated. No evidence for rearrangement near TCL1 was found in BL. Instead,
      a NotI site adjacent to the TATA box in the TCL1 promoter was found to be
      unmethylated. By contrast, tumor cell lines not expressing TCL1 were fully
      methylated at this NotI site, while normal somatic cells were hemimethylated. We
      also found that TCL1 was expressed in B-cell chronic lymphocytic leukemia (CLL)
      and the related disorder splenic lymphoma with villous lymphocytes (unlike in
      normal mature B-cells), and that the NotI site was unmethylated on both alleles.
      This correlation of repression and methylation was tested in vitro. When cells
      with both alleles methylated at the NotI site were demethylated, TCL1 expression
      was induced. These data provide evidence that in mature B-cell malignancies there
      is an alternative mechanism of TCL1 activation that apparently involves loss of
      methylation of one promoter allele. We discuss the significance of this for CLL
      tumorigenesis and for genomewide hypomethylation in CLL.

PMID- 11241787
TI  - Detection and quantification of CBFB/MYH11 fusion transcripts in patients with
      inv(16)-positive acute myeloblastic leukemia by real-time RT-PCR.
AB  - We used a newly established real-time RT-PCR assay for the quantification of the
      leukemia-specific CBFB/MYH11 transcripts in inv(16)-positive acute myeloblastic
      leukemia. CBFB/MYH11 could be quantified over a five log range, with a detection
      limit of 10 molecules of a CBFB/MYH11 plasmid and a 1:10(5) dilution of RNA of
      the inv(16)-positive ME-1 cell line, respectively. The fusion transcripts were
      also quantified in 19 patients with acute myeloblastic leukemia and an inv(16) at
      initial diagnosis. The expression of CBFB/MYH11 varied over a two log range
      without correlation to clinical response or relapse rate. In nine patients,
      CBFB/MYH11 was also quantified during/after chemotherapy and autologous or
      allogeneic stem cell transplantation. All of these patients showed a similar
      decline of CBFB/MYH11 after intensive therapy. Six of these patients are in
      complete remission with a stable low-level or absent CBFB/MYH11 expression. Three
      patients relapsed, and their CBFB/MYH11 transcripts rose again to pretreatment
      levels. In two patients, this increase in CBFB/MYH11 could be detected by real
      time PCR before hematological relapse. These data indicate that real-time RT-PCR
      can be used for the sensitive detection and quantification of CBFB/MYH11
      transcripts in the follow-up of patients with inv(16)-positive AML.

PMID- 11241788
TI  - Jumping translocations are common in solid tumor cell lines and result in
      recurrent fusions of whole chromosome arms.
AB  - Jumping translocations (JTs) and segmental jumping translocations (SJTs) are
      unbalanced translocations involving a donor chromosome arm or chromosome segment
      that has fused to multiple recipient chromosomes. In leukemia, where JTs have
      been predominantly observed, the donor segment (usually 1q) preferentially fuses
      to the telomere regions of recipient chromosomes. In this study, spectral
      karyotyping (SKY) and FISH analysis revealed 188 JTs and SJTs in 10 cell lines
      derived from carcinomas of the bladder, prostate, breast, cervix, and pancreas.
      Multiple JTs and SJTs were detected in each cell line and contributed to
      recurrent unbalanced whole-arm translocations involving chromosome arms 5p, 14q,
      15q, 20q, and 21q. Sixty percent (113/188) of JT breakpoints occurred within
      centromere or pericentromeric regions of the recipient chromosomes, whereas only
      12% of the breakpoints were located in the telomere regions. JT breakpoints of
      both donor and recipient chromosomes coincided with numerous fragile sites as
      well as viral integration sites for human DNA viruses. The JTs within each tumor
      cell line promoted clonal progression, leading to the acquisition of extra copies
      of the donated chromosome segments that often contained oncogenes (MYC, ABL,
      HER2/NEU, etc.), consequently resulting in tumor-specific genomic imbalances.
      Published 2001 Wiley-Liss, Inc.

PMID- 11241789
TI  - Genomic organization, tissue expression, and cellular localization of AF3p21, a
      fusion partner of MLL in therapy-related leukemia.
AB  - We previously identified the AF3p21 gene, a novel fusion partner of the MLL gene,
      in a patient who had developed therapy-related leukemia with t(3;11)(p21;q23).
      The AF3p21 gene encodes a protein consisting of 722 amino acids, which has an SH3
      (Src homology 3) domain, a proline-rich domain, and a bipartite nuclear
      localization signal. The protein's SH3 domain has high homology with that of FYN.
      Analysis of the DNA from the patient's leukemic cells revealed that intron 6 of
      the MLL gene was fused at a point upstream of exon 1 in the AF3p21 gene, and that
      the der(11) chromosome formed an MLL-AF3p21 fusion transcript in leukemic cells,
      whereas the der(3) chromosome did not form any fusion transcript. The AF3p21 gene
      on chromosome band 3p21 is 19 kb long and consists of 13 exons. The size of the
      mRNA of the AF3p21 gene is approximately 3.5 kb. The AF3p21 gene is widely
      expressed in normal human tissues including the bone marrow, brain, liver,
      thymus, lung, and skeletal muscle. Western blot and immunocytochemical analyses
      showed that AF3p21 protein has an apparent molecular weight of 80 kDa and is
      localized exclusively in the cell nucleus. These results suggest the possibility
      that AF3p21 protein plays a role in signal transduction in the nucleus.

PMID- 11241790
TI  - Analysis of secondary chromosomal alterations in 165 cases of follicular lymphoma
      with t(14;18).
AB  - Follicular lymphoma is characterized by the t(14;18) in up to 85% of cases.
      Almost all cases display evidence of secondary chromosomal alterations at initial
      diagnosis. The influence of recurrent secondary changes on disease progression
      has not been fully determined. The purpose of this study was to define the full
      spectrum of recurrent karyotypic events present at diagnosis in a large cohort of
      cases and to evaluate the sequence of cytogenetic evolution in relation to
      morphologic progression. A total of 165 cases of follicular lymphoma with
      t(14;18) were ascertained for which complete clinical information,
      histopathology, immunophenotype, and karyotype were available. One hundred sixty
      cases showed secondary alterations with an average of 7.9 additional changes per
      case. Recurrent alterations seen at the 10% or greater level included +X, +1q21
      q44, +7, +12q, +18q, del(1)(p36), del(6q), del(10)(q22-q24), the development of
      polyploidy and sidelines, and the presence of extra marker chromosomes and
      chromosomal additions. Changes that correlated with morphologic progression
      included del(1)(p36), del(6q), del(10)(q22-q24), +7, the total number of
      abnormalities, the number of markers and additions, and the presence of
      polyploidy. The most frequent second event arising after the t(14;18) was
      duplication of the der(18)t(14;18). This study demonstrates that the number and
      type of secondary chromosomal alterations in follicular lymphoma is highly
      variable between cases, but that a relatively small number of changes are seen
      repeatedly in different combinations. A consistent pattern of cytogenetic
      evolution could not be identified. Potentially significant gene duplications or
      amplifications may be disguised within marker chromosomes and additions.
      Additional cytogenetic investigation is required to decipher the karyotypic
      complexity associated with the progression of follicular lymphoma.

PMID- 11241791
TI  - Reassessment of childhood B-lineage lymphoblastic leukemia karyotypes using
      spectral analysis.
AB  - We studied a stratified cohort of 51 childhood B-lineage acute lymphoblastic
      leukemias (B-ALLs) to evaluate the efficiency of spectral karyotyping (SKY) in
      the detection of chromosome aberrations previously diagnosed using chromosome
      banding and/or reverse transcriptase polymerase chain reaction. Despite the small
      number of cases analyzed, several important features emerge from the study: (a)
      The result of banding analysis was revised in two-thirds of the cases. Eighty
      three chromosome anomalies previously undetected or not characterized using
      chromosome banding were identified by spectral karyotyping, even in patients with
      apparently normal karyotypes. (b) All hyperdiploidy cases showed one or more
      extra copies of chromosomes X, 14, and 21. (c) Two hidden rearrangements, a
      t(7;12)(?p12;p13), and a new translocation, a t(9;12)(q31;p13), both involving
      the TEL gene, were characterized. (d) Some cryptic rearrangements, such as the
      der(21) t(12;21) translocation, remained undetected. (e) No new recurrent
      chromosome anomalies were discovered with this technique. In conclusion, the
      present study confirms the efficiency of the SKY technique in resolving and
      characterizing many complex chromosome anomalies seen in childhood B-ALLs, but it
      raises questions about the ability of this technique to detect cryptic
      rearrangements, such as the t(12;21) translocation.

PMID- 11241792
TI  - Gain of chromosome arm 9p is characteristic of primary mediastinal B-cell
      lymphoma (MBL): comprehensive molecular cytogenetic analysis and presentation of
      a novel MBL cell line.
AB  - Primary mediastinal B-cell lymphoma (MBL) is an aggressive Non-Hodgkin's
      Lymphoma, which has been recognized as a distinct disease entity. We performed a
      comprehensive molecular cytogenetic study analyzing 43 MBLs. By comparative
      genomic hybridization (CGH), the most common aberrations were gains of chromosome
      arms 9p and Xq, which were present in 56% and 40% of cases, respectively. Based
      on the limited resolution of CGH, this technique may underestimate the real
      incidence of aberrations. Therefore, we also did an interphase cytogenetic study
      with eight DNA probes mapping to chromosome regions frequently altered in B-cell
      lymphomas. With this approach, both 9p and Xq gains were found in more than 70%
      of cases (75% and 87%, respectively). The findings were compared with results
      obtained in 308 other B-cell lymphomas. Gains in 9p were identified in only six
      of the 308 cases, and only one of these lymphomas with 9p gains was not primarily
      extranodal in origin (P < 10-(20) for CGH data and P < 10-(11) for fluorescence
      in situ hybridization data). We also present a novel MBL cell line, MedB-1, which
      carries the genetic aberrations characteristic of this entity.

PMID- 11241793
TI  - Lack of BCL10 mutations in multiple myeloma and plasma cell leukemia.
AB  - To determine whether the BCL10 mutation plays a role in the oncogenesis of plasma
      cell dyscrasias, we used polymerase chain reaction-single-strand conformation
      polymorphism (PCR-SSCP) and direct sequencing analysis and examined the genomic
      BCL10 mutations in 57 patients with multiple myeloma or plasma cell leukemia and
      52 normal bone marrow samples. We found three polymorphic sequence variants,
      either alone or in combination, at codons 5 and 8, and in intron 1 at base 58 of
      the BCL10 gene in 37 patients with plasma cell dyscrasia. Identical aberrant band
      shifts were also observed in 34 normal marrow samples. No polymorphic variants
      were identified in exon 2 or 3 in either patient or control samples, and no
      pathogenic mutations were detected. Patients with plasma cell dyscrasias in
      Taiwan appeared to have a higher frequency of polymorphisms at codon 5 and intron
      1 at base 58, and a lower frequency at codons 8 and 213. Our results suggest that
      BCL10 is not involved in the oncogenesis of plasma cell dyscrasias.

PMID- 11241794
TI  - Amplification of AML1 in childhood acute lymphoblastic leukemias.
AB  - Amplification of AML1 has been confirmed by fluorescence in situ hybridization
      analysis in two cases of childhood acute lymphoblastic leukemia. It remains to be
      elucidated whether this amplification results in up-regulation of the normal AML1
      gene product or a potentially mutant AML1 transcript.

PMID- 11241796
TI  - Hgfr/Met oncogene acts as target for gene amplification in DMBA-induced rat
      sarcomas: free chromatin fluorescence in situ hybridization analysis of amplicon
      arrays in homogeneously staining regions.
AB  - Analysis of chromosome rearrangements in tumors is an important means for
      revealing genetic pathways underlying tumorigenesis and tumor progression. In
      five of 17 DMBA-induced rat sarcomas, cytogenetic analysis had disclosed
      homogeneously staining regions (hsrs), which are generally accepted to be
      cytogenetic signs of gene amplification. Using comparative genomic hybridization
      (CGH), regional increases in DNA copy number of the proximal part of rat
      chromosome (RNO) 4 were detected in four of the tumors harboring hsrs.
      Amplification of the Hgfr/Met oncogene, located at RNO4q21.2, was detected by
      fluorescence in situ hybridization (FISH) in five tumors. In four of them, a
      number of flanking genes located in the close vicinity of Hgfr/Met, including
      Cav1 (q21.1), Wnt2 (q21.2-q21.3), and Cftr (q21.3), also were amplified, though
      amplification was seen in a lower fraction of the cells than was Hgfr/Met
      amplification. In the fifth tumor (BL150T), Hgfr/Met was amplified in all cells
      and was the sole amplified gene of those tested. In addition, the Hgfr/Met FISH
      signals in BL150T were tightly clustered and formed compact and intense spots
      compared with the signals seen in the other four tumors. Application of the free
      chromatin FISH technique to BL150T showed that the genomic Hgfr/Met probe stained
      the extended chromatin fibers of up to 1.5 Mb with an almost uninterrupted
      signal, indicating that the BL150T amplicon was build up solely of Hgfr/Met gene
      sequences. Our results suggest that the Hgfr/Met oncogene is the primary target
      for amplification in a subset of rat DMBA sarcomas.

PMID- 11241797
TI  - Getting vaccines into perspective.

PMID- 11241795
TI  - NUP98 gene rearrangements and the clonal evolution of chronic myelogenous
      leukemia.
AB  - The role of the BCR-ABL fusion gene in the pathogenesis of the chronic phase of
      chronic myelogenous leukemia (CML) has been well established. Several additional
      genetic changes have been reported to occur, at varying frequencies, during
      disease progression to "accelerated" and "blast crisis" phases. The NUP98 gene
      localized to chromosome band 11p15 has been found at the breakpoints of several
      distinct chromosomal translocations in patients with both de novo and therapy
      related myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML).
      Using combined cytogenetic and molecular analyses, we have found rearrangements
      of the NUP98 gene in the leukemic cells of two patients with Philadelphia
      chromosome-positive CML, during disease evolution. As expected, analysis of the
      t(7;11)(p15;p15) from one of the patients showed an in-frame NUP98-HOXA9 fusion.
      The fusion points were similar to previously reported NUP98-HOXA9 fusion points
      from patients with MDS/AML. Our results indicate that the NUP98 gene is an
      additional, albeit infrequent, genetic target during clonal evolution of CML.

PMID- 11241798
TI  - Transfusion-associated hepatitis not due to viral hepatitis type A or B. 1975.

PMID- 11241799
TI  - Studies of human antiviral CD8+ lymphocytes using class I peptide tetramers.
AB  - Understanding the interactions between a host and a pathogen relies crucially on
      quantitative measurements of immune responses. Until recently, measurements of
      the levels of cellular immune responses, i.e. those mediated by CD4+ and CD8+ T
      lymphocytes have depended largely on culture in vitro and subsequent measurement
      of specific functions (such as cytolysis). More recently, new technologies based
      around tetrameric class I peptide complexes (tetramers) have allowed
      immunologists to measure CD8+ T lymphocyte levels directly ex vivo and
      independently of function. Since CD8+ lymphocytes play a key role in a number of
      important human viral infections, these tools have yielded useful insights into
      the dynamics, phenotype and function of human antiviral lymphocyte populations.
      In this review we describe some of the basic aspects of the biology of virus
      specific CD8+ lymphocytes, and the current methods available to detect them. The
      use of tetramers has, in just four years, transformed our understanding of the
      immune responses against HIV, HTLV-1, HBV, HCV, CMV and EBV, and holds promise in
      a number of areas where quantitative analysis of the antiviral response in terms
      of both number and function is critical.

PMID- 11241800
TI  - Human herpesvirus-6 and -7 in transplantation.
AB  - Infections with the beta-herpesviruses human herpesvirus-6 (HHV-6) and human
      herpesvirus-7 (HHV-7) are ubiquitous in childhood. The immunosuppression
      secondary to organ or bone marrow transplantation together with
      posttransplantation management may favour viral replication and reactivation. HHV
      6 and -7 induce immunosuppression by targeting lymphocytes, natural killer cells
      and monocytes. HHV-6 is commonly detected posttransplantation but variability in
      definitions of clinical syndromes related to this virus and detection methods
      have complicated understanding of the clinical relevance of HHV-6
      posttransplantation. Clinical symptoms associated with HHV-6 include febrile
      illness, pneumonitis, hepatitis, encephalitis and bone marrow suppression.
      However, the majority of HHV-6 infections are asymptomatic. The incidence of HHV
      7 infection and its clinical manifestations posttransplantation are even less
      well characterised. In addition, HHV-6 and HHV-7 are related to CMV disease or
      acute graft-versus-host disease and, indirectly, to increases in resource
      utilisation. Based on the potential relevance of these two beta-herpesviruses in
      transplant recipients, further studies are required to establish their real
      impact in transplantation. For this, sensitive and specific molecular diagnostic
      techniques allowing for the rapid detection and quantitation of virus and for the
      analysis of susceptibility to current antiviral agents are required.

PMID- 11241801
TI  - Borna disease virus.
AB  - Borna disease virus (BDV) is unique amongst animal RNA viruses in its molecular
      biology and capacity to cause persistent, noncytolytic CNS-infection in a wide
      variety of host species. Unlike other non-segmented negative-strand RNA animal
      viruses, BDV replicates in the nucleus of the host cell where splicing is
      employed for expression of a very compact genome. Epidemiological studies
      indicate a broad host range and geographical distribution, and some investigators
      have proposed that human infection may result in neuropsychiatric disorders.
      Experimental Borna disease in neonatal and adult rats provides an intriguing
      model for immune-mediated disturbances of brain development and function.

PMID- 11241802
TI  - Planning for the next pandemic of influenza.
AB  - Worldwide influenza pandemics have occurred at irregular and unpredictable
      intervals throughout history and it is confidently expected that they will
      continue to occur in the future. It is now recognised that these pandemics result
      when avian influenza A viruses succeed in adaptation to and transmission between
      humans. The impact of pandemic influenza is substantial in terms of morbidity,
      mortality and economic cost and there is the potential for serious social
      disruption. Influenza vaccines remain the most effective defence against
      influenza but will be in short supply during a pandemic, as will the new specific
      anti-influenza drugs, due to the lead-time required for production and rapid
      spread of the virus. To minimise the impact of pandemics it is imperative to
      maximise the availability of both vaccines and antivirals and to ensure that they
      are used optimally. This requires planning at both the international and national
      levels. The World Health Organization has, therefore, developed a staged plan for
      responding to a pandemic threat which is based principally on its surveillance
      program. It has also prepared guidelines to assist national agencies in their
      planning. However, there may be further options for increasing our preparedness
      which should also be considered.

PMID- 11241803
TI  - Modulation of cerebral blood oxygenation by indomethacin: MRI at rest and
      functional brain activation.
AB  - The modulation of blood oxygenation level-dependent (BOLD) cerebral MRI contrast
      by the vasoconstrictive drug indomethacin (i.v. 0.2 mg/kg b.w.) was investigated
      in 10 healthy young adults without and with functional challenge (repetitive and
      sustained visual activation). For comparison, isotonic saline (placebo, 20 mL)
      and acetylsalicylate (i.v. 500 mg) were investigated as well, each in separate
      sessions using identical protocols. After indomethacin, dynamic T2*-weighted echo
      planar MRI at 2.0 T revealed a rapid decrease in MRI signal intensity by 2.1%
      2.6% in different gray matter regions (P < or = 0.001 compared to placebo), which
      was not observed for acetylsalicylate and the placebo condition. Regional signal
      differences were not significant within gray matter, but all gray matter regions
      differed significantly from the signal decrease of only 1.2% +/- 0.7% observed in
      white matter (P = 0.001). For the experimental parameters used, a 1% MRI signal
      decrease in response to indomethacin was estimated to correlate with a decrease
      of the cerebral blood flow by about 12 ml/100 g/minute, and an increase of the
      oxygen extraction fraction by about 15%. Responses to visual activation were not
      affected by saline or acetylsalicylate, and yielded 5.0%-5.5% BOLD MRI signal
      increases both before and after drug application. In contrast, indomethacin
      reduced the initial response strength to 82%-85% of that obtained without the
      drug. The steady-state response during sustained activation reached only 47% of
      the corresponding pre-drug level (P < 0.01). During repetitive activation the
      BOLD contrast was reduced to 66% of that observed for control conditions (P <
      0.001). In conclusion, indomethacin attenuates the vasodilatory force at
      functional brain activation, indicating different mechanisms governing
      neurovascular coupling.

PMID- 11241804
TI  - Correlation of the apparent diffusion coefficient and the creatine level in early
      ischemic stroke: a comparison of different patterns by magnetic resonance.
AB  - It has been reported that reduction of the apparent diffusion coefficient (ADC)
      after stroke can persist for several days, after which the ADC increases
      gradually to an abnormally high level. We evaluated ADC values of stroke lesions
      and compared the results to the cellular density of the lesion by means of the
      creatine (Cre) level. This two-parameter estimation is of particular relevance in
      ascertaining the underlying cellular status. Lesion-to-contralateral ADC ratios
      (ADCn) were obtained based on diffusion-weighted echo-planar and fast spin-echo
      imaging. Single-voxel localized spectroscopy was used for quantification of
      cerebral metabolites in infarcted regions. Their levels were also compared to
      that in homotopic contralateral regions. Fifteen patients with ischemic stroke
      were examined at times ranging from 18-88 hours following the onset of symptoms.
      In the stroke lesion, there was a significant correlation between the ADC and the
      Cre level showing that the higher the cell density the lower the ADC value. For
      ADCn vs. the lesion Cre concentration and the lesion-to-contralateral Cre ratio
      (Cre(n)), the strengths of relationship were R2 = 0.70 and 0.58, respectively. It
      is concluded that ADC is a good reflection of cell density. Greatly lowered ADC
      values occur within the context of a stable cellularity. ADC and the Cre level
      have complementary roles in the characterization of stroke lesion with regard to
      the sequential stage.

PMID- 11241805
TI  - Chronological analysis of physiological T2* signal change in the cerebrum during
      breath holding.
AB  - The purpose of this study was to examine which physiological factors affect
      cerebral T2* signal intensity (SI) during breath holding (BH) (apnea after
      inspiration and breathing after expiration) in normal volunteers. We examined SI
      changes caused by anoxic gas inhalation, by respiratory movements, and by BH.
      High-speed echo planar images (EPI) showed changes in SI that could be divided
      into five phases. Reports indicate that SI changes induced by BH are due to the
      effects on the magnetic susceptibility of deoxygenated hemoglobin
      (deoxyhemoglobin (dHb)) and to hypercapnia, but these reports could not fully
      explain the observed five phases. In addition to deoxyhemoglobin susceptibility
      and hypercapnia, we found that respiratory movements play a third critical role
      in modifying SI by affecting blood flow into the region of interest (ROI), as
      judged from right carotid artery flow. Consequently, we propose that the
      physiological SI changes induced by BH are derived from blood oxygenation,
      hypercapnia, and respiratory movements.

PMID- 11241806
TI  - Myocardial flow reserve parametric map, assessed by first-pass MRI compartmental
      analysis at the chronic stage of infarction.
AB  - Regional myocardial flow and flow reserve (MFR) were assessed by compartmental
      analysis of Gd-enhanced MRI first-pass data in 7 patients with atypical chest
      pain, and in 15 patients with previous transmural myocardial infarction. The FE
      product (Flow x Extraction coefficient), derived from the modified Kety equation,
      was measured in regions corresponding to the Tetrofosmine-SPECT fixed defect and
      in remote normal regions. The FE product at rest and hyperemic FE product were
      similar in healed revascularized tissues (70.5 +/- 15.6 and 112.5 +/- 19.5
      ml/mn/100 g, respectively) and in normal myocardium (76.2 +/- 18.3 and 142.2 +/-
      33.0, respectively). In contrast, the FE index (48.8 +/- 15.2 and 60.7 +/- 18.0,
      respectively, P < 0.01 versus the two previous groups) and the MFR (1.27 +/- 0.20
      vs. 1.91 +/- 0.29 in normal regions) were reduced in healed fibrotic tissues when
      the infarct-related artery remained occluded. Myocardial flow reserve maps
      allowed correct identification of regions corresponding to an occluded infarct
      related artery.

PMID- 11241807
TI  - Global myocardial blood flow and global flow reserve measurements by MRI and PET
      are comparable.
AB  - Coronary flow reserve (CFR) measurements have been widely used in assessing the
      functional significance of coronary artery stenosis because they are more
      sensitive in predicting major cardiac events than angiographically detected
      reductions of coronary arteries. Myocardial blood flow can be determined by
      measuring coronary sinus (CS) flow with velocity-encoded cine magnetic resonance
      imaging (VEC-MRI). The purpose of this study was to compare global myocardial
      blood flow (MBF) and CFR measured using VEC-MRI with MBF and CFR measured using
      positron emission tomography (PET). We measured MBF at baseline and after
      dipyridamole-induced hyperemia in 12 male volunteers with VEC-MRI and PET. With
      VEC-MRI, MBF was 0.64 +/- 0.09 (ml/min/g) at baseline and 1.59 +/- 0.79
      (ml/min/g) at hyperemia, which yielded an average CFR of 2.51 +/- 1.29. With PET,
      MBF was 0.65 +/- 0.20 (ml/min/g) at baseline and 1.78 +/- 0.72 (ml/min/g) at
      hyperemia, which yielded an average CFR of 2.79 +/- 0.97. The correlation of MBFs
      between these two methods was good (r = 0.82, P < 0.001). The CFRs measured by
      MRI correlated well with those measured using PET (r = 0.76, P < 0.004). These
      results suggest that MRI is a useful and accurate method to measure global MBF
      and CFR. Therefore, it would be suitable for studying risk factor modifications
      of vascular function at an early stage in healthy volunteers.

PMID- 11241808
TI  - Measurement of left ventricular dimensions and function in patients with dilated
      cardiomyopathy.
AB  - Studies on medical therapy in heart failure are focused on changes of left
      ventricular (LV) dimensions and function. These changes may be small, requiring a
      large study group. We measured LV parameters (LV volumes, LV ejection fraction
      (LV-EF), and left ventricular mass (LVM)) with two-dimensional echocardiography
      (2D-echo) and magnetic resonance imaging (MRI) in 50 patients. Based on the
      difference between the measurements, we determined the variance of the results
      and calculated the sample sizes needed to detect changes of baseline values. For
      the calculated and measured parameters we found significant differences between
      the two techniques: LV-EF and LVM were higher in 2D-echo, and LV dimensions were
      comparable. The sample size to detect relevant changes from baseline with MRI was
      significantly (P < 0.01) smaller than in 2D-echo. We conclude that MRI is
      superior in clinical studies on left ventricular dimensional and functional
      changes, since measurements are more reproducible and the required sample size is
      substantially smaller, thereby reducing costs.

PMID- 11241809
TI  - Dynamic 3D MR angiography of the pulmonary arteries in under four seconds.
AB  - Although 3D MRA has been shown to provide excellent depiction of the pulmonary
      arterial tree, its clinical use has been limited due to lengthy breath-holding
      requirements. Employing the newest gradient generation (1.5 T MR system,
      amplitude of 40 mT/m and a slew rate of 200 mT/m/msec), we evaluated a technique
      permitting the dynamic acquisition of 3D data sets of the entire pulmonary tree
      in under 4 seconds. Coronal image sets were collected using a repetition time of
      1.64 msec and an echo time of 0.6 msec, resulting in an acquisition time of 3.74
      seconds. Three volunteers and eight dyspneic patients with known or suspected
      pulmonary embolism underwent MRI of the pulmonary arteries. The pulmonary
      arterial tree was visible to a subsegmental level in all examined subjects.
      Regarding the presence of pulmonary emboli in four patients, there was complete
      concordance between MR angiographic findings and those of corroborative studies.
      We conclude that diagnostic MRA of the pulmonary vasculature can be obtained even
      in patients with severe respiratory distress.

PMID- 11241810
TI  - Hyperpolarized 3He MR lung ventilation imaging in asthmatics: preliminary
      findings.
AB  - Asthma is a disease characterized by chronic inflammation and reversible
      obstruction of the small airways resulting in impaired pulmonary ventilation.
      Hyperpolarized 3He magnetic resonance (MR) lung imaging is a new technology that
      provides a detailed image of lung ventilation. Hyperpolarized 3He lung imaging
      was performed in 10 asthmatics and 10 healthy subjects. Seven asthmatics had
      ventilation defects distributed throughout the lungs compared with none of the
      normal subjects. These ventilation defects were more numerous and larger in the
      two symptomatic asthmatics who had abnormal spirometry. Ventilation defects
      studied over time demonstrated no change in appearance over 30-60 minutes. One
      asthmatic subject was studied twice in a three-week period and had ventilation
      defects which resolved and appeared in that time. This same subject was studied
      before and after bronchodilator therapy, and all ventilation defects resolved
      after therapy. Hyperpolarized 3He lung imaging can detect the small, reversible
      ventilation defects that characterize asthma. The ability to visualize lung
      ventilation offers a direct method of assessing asthmatics and their response to
      therapy.

PMID- 11241811
TI  - Chronic hepatitis: correlation of early patchy and late linear enhancement
      patterns on gadolinium-enhanced MR images with histopathology initial experience.
AB  - The purposes of our study were to describe the early and late enhancement
      patterns of the liver on gadolinium-enhanced dynamic magnetic resonance (MR)
      images in patients with chronic hepatitis and to correlate these findings with
      histopathology. Patients were entered into the study based on the presence of
      chronic hepatitis, imaging evaluation with MR imaging (MRI), including early and
      late postgadolinium images, and histopathologic correlation. Early and late
      dynamic postgadolinium MR images of 29 consecutive patients with a pathologically
      proven diagnosis of chronic hepatitis were retrospectively evaluated for the
      presence of three types of enhancement, i.e., homogeneous, linear, and patchy.
      Correlation was made between the enhancement patterns on MR images and blinded
      retrospective interpretation of the histopathologic specimens, which were
      obtained within 3 months of the MR examination. Of the 29 patients, 16 (55.2%)
      patients showed patchy enhancement on the early gadolinium-enhanced MR images. In
      11 (68.8%) of these 16 patients, histopathology demonstrated numerous
      macrophages, variable hepatocyte necrosis, and increased steatosis. The remaining
      13 (44.8%) patients showed homogeneous enhancement on the early gadolinium
      enhanced MR images. In 11 (84.6%) of these 13 patients, histopathology
      demonstrated few or no macrophages, little or no hepatocellular necrosis, and
      little or no steatosis. The correlation between patchy enhancement and acute
      liver inflammation was significant (P = 0.005). On the late gadolinium-enhanced
      MR images, 20 (69.0%) of 29 patients showed prominent linear enhancement. In 19
      (95.0%) of these 20 patients, histopathology revealed hepatic fibrosis. We
      concluded that in patients with chronic hepatitis, the presence of early patchy
      enhancement indicates either concurrent or recent hepatocellular damage, whereas
      the presence of late linear enhancement indicates the presence of fibrosis, with
      a high degree of correlation with histopathologic findings.

PMID- 11241812
TI  - In vivo investigation of hepatic iron overload in rats using T2 maps:
      quantification at high intensity field (4.7-T).
AB  - In vivo quantitation of hepatic iron content is useful in diagnosis and staging
      of several iron related diseases. We used an experimental model of hepatic iron
      overload to determine the correlation between iron content and T2 relaxation time
      in rat liver. Experiments were carried out at 4.7T for high signal-to-noise ratio
      (SNR) using a spin-echo multiecho sequence with six echoes and minimum echo-time
      of 5.5 msec. The liver iron content was determined ex vivo by atomic absorption
      spectrophotometry (AAS). T2 maps were calculated in order to evaluate the space
      distribution of the iron content. We found good linear correlation between the in
      vivo liver transversal relaxation rate and the iron content within the range
      explored (106-4538 microg Fe/g liver wet wt.). T2 maps revealed that the decrease
      in T2 is not homogeneous through the liver parenchyma. This finding represents a
      physiological limitation to obtaining better correlation between T2 and iron
      content.

PMID- 11241813
TI  - Focal liver lesions: comparison of dual-phase CT and multisequence multiplanar MR
      imaging including dynamic gadolinium enhancement.
AB  - The purpose of this study was to compare dual-phase spiral computed tomography
      (CT) and magnetic resonance imaging (MRI) using dynamic gadolinium enhancement
      for liver lesion detection and characterization. Twenty-two consecutive patients
      underwent dual-phase spiral CT and MRI for the evaluation of focal liver disease
      within a 1-month period. Spiral CT and MR images were interpreted prospectively,
      in a blinded fashion by separate, individual, experienced investigators, to
      determine lesion detection and characterization. Liver lesions were confirmed by
      surgery and pathology in 6 patients, and by clinical and imaging follow-up in the
      other 16 patients. Pathological correlation of a primary extrahepatic malignancy
      was available in 5 of the 16 patients who had metastatic liver disease. Spiral CT
      and MRI detected 53 and 63 lesions, and characterized 39 and 62 true positive
      lesions, respectively. A kappa statistic test was applied to assess agreement
      between MR and CT results. MR versus CT for lesion detection resulted in a kappa
      statistic of 0.54 (95% confidence interval), indicating moderate agreement, and
      0.32 (95% confidence interval) for lesion characterization, indicating only
      slight agreement. More lesions were detected on MR images than CT images in 6
      (27%) patients, with lesions detected only on MR images in 4 (18%) patients. More
      lesions were characterized on MR images in 9 (41%) patients. In 9 patients with a
      discrepancy between MR and CT findings, the MR images added information
      considered significant to patient management in all 9 cases. MRI was moderately
      superior to dual-phase spiral CT for lesion detection, and was markedly superior
      for lesion characterization, with these differences having clinical significance.

PMID- 11241814
TI  - 3D contrast-enhanced MR angiography of the run-off vessels: value of image
      subtraction.
AB  - The diagnostic gain associated with image subtractions was assessed regarding
      contrast-enhanced 3D magnetic resonance angiography (MRA) image sets of the
      pelvic and lower extremity arteries. The MRA strategy combined a dedicated
      vascular coil with a single injection, two-station protocol. Voxel-by-voxel
      signal intensity subtraction was performed on MRA image sets obtained before and
      during dynamic infusion of a para-magnetic contrast agent. Non-subtracted and
      subtracted MRA image sets were assessed for the presence of occlusive (four
      grades) disease, using DSA as the standard of reference. In addition, SNR and CNR
      were recorded for each vascular segment on both the non-subtracted and subtracted
      images. While CNR values of subtracted images exceeded those of non-subtracted
      images (P < 0.05), there was no difference in diagnostic performance. For the
      detection of hemodynamically significant disease, non-subtracted and subtracted
      MRA provided overall sensitivity and specificity of 90.2%/90.3% and 95.1%/95.6%,
      respectively. Concordance between non-subtracted and subtracted MRA was excellent
      (Kappa = 0.86).

PMID- 11241815
TI  - Evaluation of chondromalacia of the patella with axial inversion recovery-fast
      spin-echo imaging.
AB  - The purpose of our study was to assess the accuracy of inversion recovery-fast
      spin-echo (IR-FSE) imaging for the evaluation of chondromalacia of the patella.
      Eighty-six patients were included, they underwent magnetic resonance (MR)
      examination and subsequent knee arthroscopy. Medial and lateral facets of the
      patella were evaluated separately. Axial images were obtained by using IR-FSE
      (TR/TE/TI = 3000/25/150 msec; echo train length, 8; 4-mm thickness; 12-cm field
      of view; 512 x 256 matrix; two, number of excitations) with a 1.5-T MR machine.
      MR interpretation of chondromalacia was made on the basis of the arthroscopic
      grading system. Of a total of 172 facets graded, arthroscopy revealed
      chondromalacia in 14 facets with various grades (G0, 158; G1, 1; G2, 3; G3, 6;
      G4, 4). Sensitivity, specificity, and accuracy in the chondromalacia grades were
      57.1%, 93.0%, and 90.1%, respectively. There was one false-negative case (G4) and
      11 false-positive cases (G1, eight; G2, two; G3, one). Sensitivity and
      specificity corrected by one grade difference were improved to 85.7% and 98.1%,
      respectively. When cartilage changes were grouped into early (corresponding to
      grade 1 and 2) and advanced (grade 3 and 4) diseases, sensitivity and specificity
      of the early and advanced diseases were 75% and 94% and 80% and 99%,
      respectively. IR-FSE imaging of the knee revealed high specificity but low
      sensitivity for the evaluation of chondromalacia of the patella.

PMID- 11241816
TI  - The effects of 1.5T magnetic resonance imaging on early murine in-vitro embryo
      development.
AB  - Although no ionizing radiation is involved, patients undergoing magnetic
      resonance imaging (MRI) are exposed to powerful static magnetic fields, magnetic
      field gradients, and radio-frequency fields that may be potentially damaging. Our
      study aims to document the effect of MRI imaging sequences on early murine embryo
      development (two-cell to blastocyst stage) in vitro. Two-cell murine embryos were
      exposed to various lengths of MRI using pulse sequences employed in present day
      clinical imaging. Early murine embryo development was documented in vitro, and
      blastocyst development rates were computed for both the control and exposed
      groups. There were no significant differences detected in the rate of blastocyst
      formation between the control groups and the embryos exposed to MRI.

PMID- 11241817
TI  - MRI monitoring of the thermal ablation of tissue: effects of long exposure times.
AB  - MRI-derived thermometry based on the temperature-dependence of the proton
      resonant frequency (PRF) is extremely sensitive to changes in tissue unrelated to
      temperature changes, including tissue swelling. This study investigated the
      maximum amount of time that this phase-subtraction-based method can be used to
      accurately monitor temperature changes in vivo. Long-duration focused ultrasound
      sonications were delivered in rabbit thigh muscle with a phased-array transducer,
      and the time that tissue swelling began was monitored. Tissue swelling began to
      occur at about one minute. The temperature correlated well with an implanted
      thermocouple up to this time. After this time, severe artifacts in the phase
      difference maps were observed. The thermal dose model predicted the extent of
      tissue damage well for subsequent one minute sonications. These results will have
      implications for MRI guidance of thermal therapies with long exposure times.

PMID- 11241818
TI  - A multi-scale method for automatic correction of intensity non-uniformity in MR
      images.
AB  - In this paper, a novel multi-scale method for coil sensitivity profile correction
      is presented based on wavelet transform. A magnetic resonance (MR) image can be
      decomposed into two spaces by the wavelet transform: approximate space and
      residual space. The approximate templates in approximate space can be thought of
      as multi-scale sensitivity profiles of the surface coil for coil correction. When
      we choose a suitable filter for decomposition, one of the sensitivity profiles
      should be optimal among the multi-scale sensitivity profiles. The optimal
      sensitivity profile can be chosen automatically by an analysis of the contents of
      the two spaces. The multi-scale method does not rely on any data other than the
      image generated by the MR scanner. The experiment showed promising results based
      on one-dimensional simulation and images of phantom and human images.

PMID- 11241819
TI  - Temperature quantification using the proton frequency shift technique: In vitro
      and in vivo validation in an open 0.5 tesla interventional MR scanner during RF
      ablation.
AB  - Open magnetic resonance (MR) scanners allow MR-guided targeting of tumors, as
      well as temperature monitoring of radio frequency (RF) ablation. The proton
      frequency shift (PFS) technique, an accurate and fast imaging method for
      temperature quantification, was used to synthesize thermal maps after RF ablation
      in an open 0.5 T MR system under ex vivo and in vivo conditions. Calibration
      experiments with 1.5% agarose gel yielded a chemical shift factor of 0.011 +/-
      0.001 ppm/ degrees C (r2 = 0.96). Three gradient echo (GRE) pulse sequences were
      tested for thermal mapping by comparison with fiberoptic thermometer (Luxtron
      Model 760) readings. Temperature uncertainty decreased from high to low
      bandwidths (BW): +/-5.9 degrees C at BW = 15.6 kHz, +/-1.4 degrees C at BW = 3.9
      kHz, and +/-0.8 degrees C at BW = 2.5 kHz. In vitro experiments (N = 9) in the
      paraspinal muscle yielded a chemical shift factor of 0.008 +/- 0.001 ppm/ degrees
      C. Temperature uncertainty was determined as +/-2.7 degrees C (BW = 3.9 kHz, TE =
      19.3 msec). The same experiments carried out in the paraspinal muscle (N = 9) of
      a fully anesthetized pig resulted in a temperature uncertainty of +/-4.3 degrees
      C (BW = 3.9 kHz, TE = 19.3 msec), which is higher than it is in vitro conditions
      (P < 0.15). Quantitative temperature monitoring of RF ablation is feasible in a
      0.5 T open-configured MR scanner under ex vivo and in vivo conditions using the
      PFS technique.

PMID- 11241820
TI  - Precision of magnetic resonance velocity and acceleration measurements:
      theoretical issues and phantom experiments.
AB  - Magnetic resonance (MR) sequences have been developed for acquiring multiple
      components of velocity and/or acceleration in a reasonable time and with a single
      acquisition. They have many parameters that influence the precision of
      measurements: NS, the number of flow-encoding steps; NEX, the number of signal
      accumulations; and ND, the number of dimensions. Our aims were to establish a
      general relationship revealing the precision of these measurements as a function
      of NS, ND, and NEX and to validate it by experiments using phantoms. Previous
      work on precision has been restricted to two-step (NS = 2) or 1D (ND = 1) MR
      velocity measurements. We describe a comprehensive approach that encompasses both
      multistep and multidimensional strategies. Our theoretical formula gives the
      precision of velocity and acceleration measurements. It was validated
      experimentally with measurements on a rotating disk phantom. This phantom was
      much easier to handle than fluid-based phantoms. It could be used to assess both
      velocity and acceleration sequences and provided accurate and precise assessments
      over a wide, adjustable range of values within a single experiment. Increasing
      each of the three parameters, NS, ND, and NEX, improves the precision but makes
      the acquisition time longer. However, if only one parameter is to be assessed,
      maximizing the number of steps (NS) is the most efficient way of improving the
      precision of measurements; if several parameters are of interest, they should be
      measured simultaneously. By contrast, increasing the number of signals
      accumulated (NEX) is the least efficient strategy.

PMID- 11241821
TI  - Prospective stereotaxy: a novel method of trajectory alignment using real-time
      image guidance.
AB  - PURPOSE: To describe prospective stereotaxy, a novel method of trajectory
      alignment that works in real-time. MATERIALS AND METHODS: Prospective stereotaxy
      was used in minimally-invasive neurosurgical procedures in 74 patients since
      February 1999. This methodology differs from framed and frameless stereotaxy,
      both of which are based on retrospective data. Rather, prospective stereotaxy
      uses real-time MR images to align a surgical trajectory. RESULTS: Phantom tests
      and clinical procedures in all patients were successfully performed using
      prospective stereotaxy. In all cases, surgical targets were accessed, and the
      diagnostic yield of neurobiopsy using prospective stereotaxy was 100%.
      CONCLUSION: Prospective stereotaxy is applicable to all cross-sectional imaging,
      and is particularly useful for MR- and CT-guided interventions. The method is
      simple, reproducible, and accurate in surgical targeting for neurobiopsy and
      electrode placement. It does not require cumbersome stereotactic frames or
      expensive optical detectors, and it offers immediate entry into the field of
      interventional MR with cylindrical MR scanners.

PMID- 11241822
TI  - Pulmonary arteriovenous malformation: Characterization with time-resolved
      ultrafast 3D MR angiography.
AB  - To avoid potentially deadly consequences from paradoxical emboli, early detection
      and accurate characterization of pulmonary arteriovenous malformations (AVMs) is
      highly desirable. We report on a patient with a suspected pulmonary AVM who
      underwent ultrafast time-resolved 3D MR angiography of the pulmonary arteries.
      The case documents the suitability of the MRA technique as a noninvasive
      alternative to computed tomographic angiography and digital subtraction
      angiography for accurate pre-therapeutic characterization of pulmonary AVMs.

PMID- 11241823
TI  - Feasibility of endocardial edge detection by using an inversion recovery
      artifact.
AB  - An inversion recovery (IR) artifact was used to delineate the blood/wall boundary
      in left ventricles. The artifact consisted of a hypointensity signal in pixels
      located at the boundary of two contiguous tissues with different T(1) relaxation
      times. The feasibility of measuring the ejection fraction using the artifact was
      tested in ten healthy volunteers, with two IR snapshot-FLASH sequences possessing
      different times of repetition (TR = 11msec and TR = 3.5msec) and appropriate
      times of inversion. The comparison with a cine-MRI sequence showed that ejection
      fraction measurements are feasible when performed with a snapshot-FLASH sequence
      that has a sufficiently short TR (3.5msec).

PMID- 11241824
TI  - Determination of regional pulmonary parenchymal strain during normal respiration
      using spin inversion tagged magnetization MRI.
AB  - In clinical practice, the assessment of lung mechanics is limited to a global
      physiological evaluation, which measures, in the aggregate, the contributions of
      the pulmonary parenchyma, pleura, and chest wall. In this study, we used an MR
      imaging methodology which applies two-dimensional bands of inverted magnetization
      directly onto the pulmonary parenchyma, thus allowing for the quantification of
      local pulmonary tissue deformation, or strain, throughout inhalation. Our results
      showed that the magnitude of strain was maximal at the base and apex of the lung,
      but was curtailed at the hilum, the anatomical site of the poorly mobile
      bronchial and vascular insertions. In-plane shear strain mapping showed mostly
      positive shear strain, predominant at the apex throughout inhalation, and
      increasing with expanding lung volume. Anisotropy mapping showed that superior
      inferior axial strain was greater than medial-lateral axial strain at the apex
      and base, while the opposite was true for the middle lung field. This study
      demonstrates that localized pulmonary deformation can be measured in vivo with
      tagging MRI, and quantified by applying finite strain definitions from continuum
      mechanics.

PMID- 11241825
TI  - Improved multi-station peripheral MR angiography with a dedicated vascular coil.
AB  - Delineation of small branch vessels can be crucial for assessing the peripheral
      arterial system of patients requiring surgical grafting. Thus signal-to-noise
      needs to be maximized. We evaluated the performance of a dedicated peripheral
      vascular coil in four subjects by comparing it to the body coil using DSA as the
      standard of reference. SNR and CNR values of the dedicated peripheral coil
      exceeded those obtained with the body coil by a mean of 398%, thus permitting
      improved delineation of the infrapopliteal arterial morphology.

PMID- 11241828
TI  - Responsiveness to neurturin of subpopulations of embryonic rat spinal motoneuron
      does not correlate with expression of GFR alpha 1 or GFR alpha 2.
AB  - Glial cell-line derived neurotrophic factor (GDNF) and its relative neurturin
      (NTN) are both potent trophic factors for motoneurons. They exert their
      biological effects by activating the RET tyrosine kinase in the presence of a GPI
      linked coreceptor, either GFR alpha 1 (considered to be the favored coreceptor
      for GDNF) or GFR alpha 2 (the preferred NTN coreceptor). By whole-mount in situ
      hybridization on embryonic rat spinal cord, we demonstrate that, whereas Ret is
      expressed by nearly all motoneurons, Gfra1 and Gfra2 exhibit complementary and
      sometimes overlapping patterns of expression. In the brachial and sacral regions,
      the majority of motoneurons express Gfra1 but only a minority express Gfra2.
      Accordingly, most motoneurons purified from each region are kept alive in culture
      by GDNF. However, brachial motoneurons respond poorly to NTN, whereas NTN
      maintains as many sacral motoneurons as does GDNF. Thus, spinal motoneurons are
      highly heterogeneous in their expression of receptors for neurotrophic factors of
      the GDNF family, but their differing responses to NTN are not correlated with
      expression levels of Gfra1 or Gfra2.

PMID- 11241829
TI  - Early developmental expression pattern of retinoblastoma tumor suppressor mRNA
      indicates a role in the epithelial-to-mesenchyme transformation of endocardial
      cushion cells.
AB  - The earliest stages of embryonic development are characterized by the generation
      of precursor cell populations that differentiate and coalesce into tissue and
      organ primordia. To provide sufficient numbers of differentiated cells for tissue
      and organ formation, the differentiative as well as the proliferative processes
      of cells must be controlled and coordinated. Potential regulators of the
      proliferative process include molecules that control the cell cycle, in
      particular, the tumor suppressor proteins. To begin to understand the role such
      molecules can play in development, we have studied the expression of the
      retinoblastoma tumor suppressor (Rb) gene in early chicken development. Our
      studies in early chicken embryos show that Rb is encoded by a single gene that
      gives rise to several Rb mRNA isoforms through alternative splicing of a primary
      transcript. These mRNA isoforms potentially encode Rb proteins that differ with
      respect to the number of sequence motifs known to target cyclin-dependent kinases
      to Rb, suggesting dynamic control of Rb phosphorylation and function during
      development. This complex expression pattern of Rb mRNA begins as early as the
      blastoderm stage of chicken development (stage 3) and continues through stage 18,
      the latest stage examined. Despite this early embryonic expression of Rb mRNA as
      detected by reverse transcription polymerase chain reaction, Rb mRNA levels
      sufficient to be detected by in situ hybridization were not expressed until after
      stage 14 of development. Rb mRNA was found to be localized to cells of the
      endocardial cushions of the early heart tube, cells of the epicardium, and
      myogenic cells of the somitic myotome. Interestingly, each of these cell types
      undergoes an epithelial-to-mesenchyme transformation to form a migratory and/or
      invasive population of mesenchymal cells. We have focused our studies on the
      expression of Rb mRNA in endocardial cells of the early heart tube, because the
      transition of these cells to mesenchyme initiates the important process of
      septation, an early step in the formation of heart valves.

PMID- 11241830
TI  - Hyperpigmentation in the Silkie fowl correlates with abnormal migration of fate
      restricted melanoblasts and loss of environmental barrier molecules.
AB  - In most homeothermic vertebrates, pigment cells are confined to the skin. Recent
      studies show that the fate-restricted melanoblast (pigment cell precursor) is the
      only neural crest lineage that can exploit the dorsolateral path between the
      ectoderm and somite into the dermis, thereby excluding neurons and glial cells
      from the skin. This does not explain why melanoblasts do not generally migrate
      ventrally into the region where neurons and glial cell derivatives of the neural
      crest differentiate, or why melanoblasts do not escape from the dorsolateral path
      once they have arrived at this destination. To answer these questions we have
      studied melanogenesis in the Silkie fowl, which is a naturally occurring chicken
      mutant in which pigment cells occupy most connective tissues, thereby giving them
      a dramatic blue-black cast. By using markers for neural crest cells (HNK-1) and
      melanoblasts (Smyth line serum), we have documented the development of the Silkie
      pigment pattern. The initial dispersal of melanoblasts is the same in the Silkie
      fowl as in Lightbrown Leghorn (LBL), White Leghorn (WLH), and quail embryos.
      However, by stage 22, when all ventral neural crest cell migration has ceased in
      the WLH, melanoblasts in the Silkie embryo continue to migrate between the neural
      tube and somites to occupy the sclerotome. This late ventral migration was
      confirmed by filling the lumen of the neural tube with DiI at stage 19 and
      observing the embryos at stage 26. No DiI-labeled cells were observed in the
      sclerotome of LBL embryos, whereas in the Silkie embryos DiI-filled cells were
      found as far ventral as the mesentery. In addition to this extensive ventral
      migration, we also observed considerable migration of melanoblasts from the
      distal end of the dorsolateral space into the somatic mesoderm (the future
      parietal peritoneum), and into the more medioventral regions where they
      accumulated around the dorsal aorta and the kidney. The ability of melanoblasts
      in the Silkie embryos to migrate ventrally along the neural tube and medially
      from the dorsolateral space is correlated with a lack of peanut agglutinin (PNA) 
      binding barrier tissues, which are present in the LBL embryo. The abnormal
      pattern of melanoblast migration in the Silkie embryo is further exaggerated by
      the fact that the melanoblasts continue to divide, as evidenced by BrdU
      incorporation (but the rate of incorporation is not greater than seen in the
      LBL). Results from heterospecific grafting studies and cell cultures of WLH and
      Silkie neural crest cells support the notion that the Silkie phenotype is brought
      about by an environmental difference rather than a neural crest-specific defect.
      We conclude that melanoblasts are normally constrained to migrate only in the
      dorsolateral path, and once in that path they generally do not escape it. We
      further conclude that the barriers that normally restrain melanoblast migration
      in the chicken are not present in the Silkie fowl. We are now actively
      investigating the nature of this barrier molecule to complete our understanding
      of melanoblast migration and patterning.

PMID- 11241831
TI  - Theoretical model for myocardial trabeculation.
AB  - During the morphogenetic process of myocardial trabeculation, most of the cardiac
      jelly of the initially smooth-walled heart is replaced by sponge-like muscle. The
      mechanisms that drive and regulate this important process are poorly understood.
      Using a theoretical model, we examined the possible role that cytoskeletal
      contraction plays during the initial stages of trabeculation. The myocardium is
      modeled as a thin viscoelastic membrane consisting of contractile (stress) fibers
      embedded in an isotropic incompressible matrix, with the interaction of
      myocardial cells and cardiac jelly fibers providing long-range mechanical
      effects. The stress fibers are assumed to behave like smooth muscle and to
      normally operate on the descending limb of their stress-stretch curve. Mechanical
      instability due to the effectively negative stiffness then leads to the creation
      of pattern. As a first approximation, computations were carried out for a flat
      rectangular membrane with stress fibers aligned along a single direction. The
      computed deformation patterns depend strongly on the magnitude and anisotropy of
      the long-range effects. Given plausible assumptions about the mechanical
      properties of the embryonic heart, the model predicts trabecular patterns similar
      to those observed in the embryo, including the development of circumferential
      ridges and relatively thin regions ("holes") in the trabecular sheets.

PMID- 11241832
TI  - Expression and regulation of chicken fibroblast growth factor homologous factor
      (FHF)-4 during craniofacial morphogenesis.
AB  - Fibroblast growth factor homologous factors (FHFs) have been implicated in limb
      and nervous system development. In this paper we describe the expression of the
      cFHF-4 gene during chicken craniofacial development. cFHF-4 is expressed in the
      mesenchyme of the frontonasal process, and in the mesenchyme and ectoderm of the
      mandibular processes. The expression of cFHF-4 and other genes implicated in
      facial patterning have been analyzed in talpid(2) embryos or in the presence of
      exogenous retinoic acid. Talpid(2) mutants show abnormal patterns of gene
      expression, including up-regulation of cFHF-4 in the developing face, which
      correlate with defects in cartilage formation. By contrast, expression of cFHF-4
      in the developing face is strongly downregulated by teratogenic doses of all
      trans retinoic acid in a dose-dependent manner. Low levels of retinoic acid that
      produce distal upper beak truncations do not affect cShh, c-Patched-1, or c-Bmp-2
      expression in the face, but downregulate cFHF-4 in the frontonasal process.

PMID- 11241833
TI  - Differential expression of plexin-A subfamily members in the mouse nervous
      system.
AB  - Plexins comprise a family of transmembrane proteins (the plexin family) which are
      expressed in nervous tissues. Some plexins have been shown to interact directly
      with secreted or transmembrane semaphorins, while plexins belonging to the A
      subfamily are suggested to make complexes with other membrane proteins,
      neuropilins, and propagate chemorepulsive signals of secreted semaphorins of
      class 3 into cells or neurons. Despite that much information has been gathered on
      the plexin-semaphorin interaction, the role of plexins in the nervous system is
      not well understood. To gain insight into the functions of plexins in the nervous
      system, we analyzed spatial and temporal expression patterns of three members of
      the plexin-A subfamily (plexin-A1, -A2, and -A3) in the developing mouse nervous
      system by in situ hybridization analysis in combination with
      immunohistochemistry. We show that the three plexins are differentially expressed
      in sensory receptors or neurons in a developmentally regulated manner, suggesting
      that a particular plexin or set of plexins is shared by neuronal elements and
      functions as the receptor for semaphorins to regulate neuronal development.

PMID- 11241834
TI  - Nuclear translocation of antizyme and expression of ornithine decarboxylase and
      antizyme are developmentally regulated.
AB  - The polyamines are important regulators of cell growth and differentiation. Cells
      acquire polyamines by energy-dependent transport and by synthesis where the
      highly regulated ornithine decarboxylase (ODC) catalyzes the first and rate
      controlling step. Inactivation of ODC is mainly exerted by antizyme (AZ), a 20-
      25 kDa polyamine-induced protein that binds to ODC, inactivates it, and targets
      it for degradation by the 26S proteasome without ubiquitination. In the present
      study, we have performed a systematic analysis of the expression of ODC and AZ,
      at the mRNA and protein levels, during mouse development. The expression patterns
      for ODC and AZ were found to be developmentally regulated, suggesting important
      functions for the polyamines in early embryogenesis, axonogenesis, epithelial
      mesenchymal interaction, and in apoptosis. In addition, AZ protein was found to
      translocate to the nucleus in a developmentally regulated manner. The nuclear
      localization is consistent with the fact that the amino acid sequence of AZ
      exhibits features that characterize nuclear proteins. Interestingly, we found
      that cultivation of mandibular components of the first branchial arch in the
      presence of a selective proteasome inhibitor caused ODC accumulation in the
      nucleus of a subset of cells, suggesting that the observed nuclear translocation
      of AZ is linked to proteasome-mediated ODC degradation in the nucleus. The
      presence of AZ in the nucleus may suggest that nuclear ODC activity is under
      tight control, and that polyamine production can be rapidly interrupted when
      those developmental events, which depend on access to nuclear polyamines, have
      been completed.

PMID- 11241835
TI  - Restricting Bmp-4 mediated apoptosis in hindbrain neural crest.
AB  - The segregation of the rhombencephalic neural crest into three streams, destined
      for particular pharyngeal arches, is a prominent feature of the developing
      vertebrate head and is likely necessary for normal morphogenesis. At least in
      part, the segregation of the crest into these streams involves the focal
      depletion of neural crest from rhombomeres 3 and 5 through large-scale apoptosis,
      mediated by the induction of Bmp-4 expression in the crest primordia of these two
      rhombomeres. Previously we found that in contrast to rhombomeres 3 and 5, the
      intervening segment rhombomere 4 was not susceptible to Bmp-4-sponsored neural
      crest cell death. To analyse the reason for this difference, we have isolated
      clones for the necessary components of the Bmp-4 signal transduction apparatus.
      We find that the hindbrain neural crest generally is primed to respond to Bmp-4
      and that in vitro, besides rhombomere 3 and 5, rhombomeres 2 and 6 are also
      sensitive to Bmp-4-sponsored death. As before, however, we find that rhombomere 4
      will not respond to this factor. Our analysis of the Bmp-4 antagonists has
      uncovered a reason for this. Rhombomere 4 expresses elevated levels of the
      antagonist Noggin at its dorsal midline just as crest production from this
      segment commences and, as development proceeds, in the crest that migrates away
      from there. At these later stages, expression also becomes apparent in the
      migratory post-otic crest as it flows by the otic vesicle. An interesting feature
      of these domains of Noggin expression is that they lie between territories of Bmp
      4 expression, suggesting that Noggin is acting to protect from Bmp-4-mediated
      cell death.

PMID- 11241836
TI  - Improved method for chick whole-embryo culture using a filter paper carrier.
AB  - We describe a simple method of chick whole-embryo culture, which uses a filter
      paper carrier to hold the early blastoderm and vitelline membranes under tension
      while the embryo grows on a substratum of agar-albumen. This is a quick and
      efficient means of setting up cultures of chick embryos beginning at pre
      primitive streak stages to stage 10 (stages X--XIV, Eyal-Giladi and Kochav [1976]
      Dev Biol 49:321-337; stages 1--10, Hamburger and Hamilton [1951] J Morphol 88:49-
      92). This is an improvement on the original method of New, which used a glass
      ring and watch glass (New [1955] Exp Morphol 3:320--331). Our modification of
      New's method, which we call EC (Early Chick, pronounced EASY) culture,
      facilitates several manipulations in early chick embryos, including microsurgery,
      grafting, bead implantation, microinjection, and electroporation. Using the EC
      method, embryos at stage 8 and older can be readily cultured either dorsal-side
      up (in contrast to New's method) or ventral-side up, as desired; embryos younger
      than stage 8 can be culture only ventral-side up (as with New's method). We also
      discuss some alternative methods for setting up these cultures.

PMID- 11241837
TI  - The Viktor Hamburger centenary celebration.

PMID- 11241838
TI  - Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene
      (SLC26A2): 22 novel mutations, mutation review, associated skeletal phenotypes,
      and diagnostic relevance.
AB  - Mutations in the DTDST gene can result in a family of skeletal dysplasia
      conditions which comprise two lethal disorders, achondrogenesis type 1B (ACG1B)
      and atelosteogenesis type 2 (AO2); and two non-lethal disorders, diastrophic
      dysplasia (DTD) and recessive multiple epiphyseal dysplasia (rMED). The gene
      product is a sulfate-chloride exchanger of the cell membrane. Inactivation of the
      sulfate exchanger leads to intracellular sulfate depletion and to the synthesis
      of undersulfated proteoglycans in susceptible cells such as chondrocytes and
      fibroblasts. Genotype-phenotype correlations are recognizable, with mutations
      predicting a truncated protein or a non-conservative amino acid substitution in a
      transmembrane domain giving the severe phenotypes, and non-transmembrane amino
      acid substitutions and splice site mutations giving the milder phenotypes. The
      clinical phenotype is modulated strictly by the degree of residual activity. Over
      30 mutations have been observed, including 22 novel mutations reported here. The
      most frequent mutation, 862C>T (R279W), is a mild mutation giving the rMED
      phenotype when homozygous and mostly DTD when compounded; occurrence at a CpG
      dinucleotide and its panethnic distribution suggest independent recurrence.
      Mutation IVS1+2T>C is the second most common mutation, but is very frequent in
      Finland. It produces low levels of correctly spliced mRNA, and results in DTD
      when homozygous. Two other mutations, 1045-1047delGTT (V340del) and 558C>T
      (R178X), are associated with severe phenotypes and have been observed in multiple
      patients. Most other mutations are rare. Heterozygotes are clinically unaffected.
      When clinical samples are screened for radiologic and histologic features
      compatible with the ACG1B/AO2/DTD/rMED spectrum prior to analysis, the mutation
      detection rate is high (over 90% of alleles), and appropriate genetic counseling
      can be given. The sulfate uptake or sulfate incorporation assays in cultured
      fibroblasts have largely been replaced by mutation analysis, but may still be
      useful in cases where mutation analysis is not informative. Although
      supplementation of patients' cultured cells with thiols may bypass the
      transporter defect and enhance sulfation of proteoglycans, therapeutic approaches
      are not yet available. Mouse models for this and other disorders of sulfate
      metabolism are being developed to help in developing therapeutic treatments.

PMID- 11241839
TI  - Mutations in the human DHCR7 gene.
AB  - The Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive metabolic
      disorder characterized by variable congenital malformations, facial dysmorphism,
      and mental retardation. Mutations in the DHCR7 gene have been identified in SLOS
      patients. This gene encodes for the enzyme Delta7-sterol reductase which
      catalyses the last step of cholesterol biosynthesis. Among the 73 different
      mutations observed so far, including 10 novel mutations reported in this review,
      the majority are missense mutations (65) which cluster in three domains of the
      protein: in the transmembrane domain (TM mutations), in the fourth cytoplasmic
      loop (4L mutations), and at the C-terminus (CT mutations). Two nonsense
      mutations, one splice site mutation, two single nucleotide insertions, and three
      deletions which likely all represent null mutations were also described.
      Expression studies have demonstrated a decreased protein stability for all
      analyzed missense mutations. By comparing clinical severity scores, biochemical
      data, and mutations in SLOS patients a genotype-phenotype correlation has been
      established. The null and 4L mutations are associated with a severe clinical
      phenotype, and TM and CT mutations are associated with a mild clinical phenotype.
      DHCR7 mutational spectra in SLOS patients of British, German, Italian, and Polish
      origin demonstrate significant geographic frequency differences of common DHCR7
      mutations.

PMID- 11241840
TI  - Mutation spectrum in patients with Rett syndrome in the German population:
      Evidence of hot spot regions.
AB  - Mutations in the MECP2 (Methyl-CpG-binding protein) gene recently have been
      reported to cause Rett syndrome (RTT), an X-linked dominant neurodevelopmental
      disease. We investigated 125 sporadic cases of Rett syndrome by direct
      sequencing. Thirty different mutations were found in 97 patients with Rett
      syndrome. Seventeen mutations have not been described previously. We provide
      evidence for the existence of several hot spot regions and of a deletion-prone
      region located at the 3' most region of the gene. This latter region most
      probably forms secondary structures in vitro. Similar structures in vivo could
      explain the high frequency of deletions in this region. Nine of 10 recurrent
      mutations were located in either the methyl CpG binding domain (MBD) or in the
      transcriptional repression domain (TRD), and all missense mutations were located
      in one of these functionally important domains. There was a high frequency of
      more than 60% of truncating mutations (nonsense mutations along with frameshift
      mutations). One patient with a mild form of the disease and a normal head growth
      carries a novel c.27-6C>A mutation that causes a cryptic splice site in intron I
      resulting in a frameshift transcript. The detection rate in our collective was
      77.6%. Our findings show that the majority of German Rett patients carry
      mutations in the MECP2 gene confirming the suggested locus homogeneity for the
      disease.

PMID- 11241841
TI  - Glucocerebrosidase pseudogene variation and Gaucher disease: Recognizing
      pseudogene tracts in GBA alleles.
AB  - We surveyed the genetic variability of the glucocerebrosidase pseudogene (psGBA)
      in a worldwide sample of 100 human chromosomes. psGBA is the non-functional
      duplicate of the gene responsible for Gaucher disease (GBA), the most common
      lipid storage disorder. The existence of only one psGBA allele described until
      now, together with the high homology between GBA and psGBA, often prevented
      recognition of the complex alleles formed by the combination of GBA and psGBA,
      because psGBA variants could be confused with GBA mutations. In order to
      determine the variability existent in psGBA, the whole psGBA DNA segment was PCR
      amplified and sequenced, and the genotype for all samples was obtained. The
      ascertainment of the phase among the heterozygous sites was possible through
      cloning and sequencing a single allele. Eighteen variable sites were detected
      along psGBA. Two of the variants already have been reported as Gaucher-causing
      mutations when present in GBA alleles. The other variants were unknown. The
      knowledge of the psGBA variants described in this report will allow
      identification of psGBA-GBA complex alleles that may aid in understanding the
      intricate phenotype-genotype relationship in Gaucher disease.

PMID- 11241842
TI  - Molecular analysis of acid ceramidase deficiency in patients with Farber disease.
AB  - Farber disease is a rare, autosomal recessively inherited sphingolipid storage
      disorder due to the deficient activity of lysosomal acid ceramidase, leading to
      the accumulation of ceramide in cells and tissues. Here we report the
      identification of six novel mutations in the acid ceramidase gene causing Farber
      disease: three point mutations resulting in single amino acid substitutions, one
      intronic splice site mutation resulting in exon skipping, and two point mutations
      also leading to occasional or complete exon skipping. Of interest, these latter
      two mutations occurred in adjacent nucleotides and led to abnormal splicing of
      the same exon. Expression of the mutated acid ceramidase cDNAs in COS-1 cells and
      subsequent determination of acid ceramidase residual enzyme activity demonstrated
      that each of these mutations was the direct cause of the acid ceramidase
      deficiency in the respective patients. In contrast, two known polymorphisms had
      no effect on acid ceramidase activity. Metabolic labeling studies in fibroblasts
      of four patients showed that even though acid ceramidase precursor protein was
      synthesized in these individuals, rapid proteolysis of the mutated, mature acid
      ceramidase occurred within the lysosome.

PMID- 11241843
TI  - Random mutagenesis-PCR to introduce alterations into defined DNA sequences for
      validation of SNP and mutation detection methods.
AB  - Sensitive and high throughput techniques are required for the detection of DNA
      sequence variants such as single nucleotide polymorphisms (SNPs) and mutations.
      One problem, common to all methods of SNP and mutation detection, is that
      experimental conditions required for detection of DNA sequence variants depend on
      the specific DNA sequence to be analyzed. Although algorithms and other
      calculations have been developed to predict the experimental conditions required
      to detect DNA sequence variation in a specific DNA sequence, these algorithms do
      not always provide reliable information and experimental conditions for SNP and
      mutation detection must be devised empirically. Determination of experimental
      conditions for detection of DNA sequence variation is difficult when samples
      containing only wild type sequence are available. When patient derived positive
      controls are used, increasingly there are valid concerns about commercial
      ownership and patient privacy. This report presents a rapid and efficient method,
      employing random mutagenesis-PCR (RM-PCR) using low fidelity DNA polymerase, to
      randomly introduce single and multiple base substitutions and deletions into DNA
      sequences of interest. Clones with sequence changes were used to validate
      denaturing HPLC (DHPLC) algorithm predictions, optimize conditions for mutation
      detection in exon 15 of the tyrosine kinase domain of the MET proto-oncogene, and
      to confirm the association between specific DNA sequence changes and unique DHPLC
      chromatographic profiles (signatures). Finally, DNA from 33 papillary renal
      carcinoma (PRC) patients was screened for mutations in exon 15 of MET using
      "validated" DHPLC conditions as a proof of principle application of RM-PCR. Use
      of RM-PCR for DHPLC and other SNP/mutation detection methods is discussed along
      with challenges associated with detecting sequence alterations in mixed
      tumor/normal tissue, pooled samples, and from regions of the genome that have
      been amplified during tumorigenesis or duplicated during evolution. Hum Mutat
      17:210-219, 2001. Published 2001 Wiley-Liss, Inc.

PMID- 11241845
TI  - Low level mosaicism detectable by DHPLC but not by direct sequencing.

PMID- 11241844
TI  - An improved high throughput heteroduplex mutation detection system for screening
      BRCA2 mutations-fluorescent mutation detection (F-MD).
AB  - We describe an improved, fast, automated method for screening large genes such as
      BRCA2 for germline genomic mutations. The method is based on heteroduplex
      analysis, and has been adapted for a high throughput application by combining the
      fluorescent technology of automated sequencers and robotic sample handling. This
      novel approach allows the entire BRCA2 gene to be screened with appropriate
      overlaps in four lanes of an ABI 377 gel. The method will detect all types of
      mutations, especially point mutations, more reliably and robustly than other
      commonly used conformational sensitive methods (e.g. CSGE). In addition we show
      that this approach, which relies on band shift detection, is able to detect
      single base substitutions that have hitherto only been detectable by direct
      sequencing methods.

PMID- 11241846
TI  - Identification of novel VMD2 gene mutations in patients with best vitelliform
      macular dystrophy.
AB  - ABSTRACT We report five novel VMD2 mutations in Best's macular dystrophy patients
      (S16F, I73N, R92H, V235L, and N296S). An SSCP analysis of the VMD2 11 exons
      revealed electrophoretic mobility shifts exclusively in exons 2, 3, 4, 6 and 8.
      Direct sequencing indicated that these shifts are caused by mono-allelic
      transition in exons 2, 4, 6, 8 and transversion in exons 3 and 6. Five novel
      "silent" polymorphisms are also reported: 213T>C, 323C>A, 1514A>G, 1661C>T, and
      1712T>C. Hum Mutat 17:235, 2001.

PMID- 11241847
TI  - Eosinophilic peroxidase deficiency: Identification of a point mutation (D648N)
      and prediction of structural changes.
AB  - ABSTRACT Hereditary eosinophil peroxidase (EPO; EC 1.11.1.7) deficiency is a rare
      abnormality without clinical symptoms characterized by decreased or absent
      peroxidase activity and decreased volume of the granule matrix in eosinophils.
      Nearly 100 cases have been reported, but a specific mutation has been reported in
      only one case. We report the genetic analysis of an EPO-deficient subject and his
      family. The case was found by automated blood analyzer. Sequencing of the entire
      coding region of the EPO gene disclosed a novel mutation, a 2060 G-A transition
      (g. 2060G>A) causing an amino acid change from aspartic acid to asparagine
      (D648N). Both the son and daughter of the propositus inherited the G-A
      transition, and in vitro expression experiments suggest this transition is
      responsible for the deficiency. We then analyzed the location of the affected
      amino acid within this molecule using a structural model of EPO based on
      myeloperoxidase (MPO). Asn648 is on the inside of the molecule; changing D to N
      would cause loss of the electrostatic interaction with Arg146 which is crucial
      for disulfide bonds of the light chain in the N terminus.

PMID- 11241848
TI  - Exonic SNPs at positions 220 (A/G) and 445 (C/T) of the peripheral myelin protein
      2 (PMP2).

PMID- 11241849
TI  - Identification of three novel menin mutations (c.741delGTCA, c.1348T>C,
      c.1785delA) in unrelated Italian families affected with multiple endocrine
      neoplasia type 1: Additional information for mutational screening.

PMID- 11241850
TI  - Two novel polymorphisms (c954T>C and c1038A>G) in exon8 of NPHS2 gene identified
      in Taiwan Chinese.

PMID- 11241851
TI  - Identification of a novel three-nucleotide insertion mutation (c.841-842insTGA)
      in the acid beta-glucosidase gene of a Taiwan Chinese patient with type II
      Gaucher disease.

PMID- 11241852
TI  - Identification of a novel mutation in the ryanodine receptor gene (RYR1) in
      patients with malignant hyperthermia.

PMID- 11241853
TI  - A new human mtDNA polymorphism: MTND6: 14562 (C-->T).

PMID- 11241854
TI  - Hypervariable area in the 5' flanking region of GSTP1, previously reported as a
      minisatellite ATAAA repeat.

PMID- 11241855
TI  - A novel splice site mutation (3157+1G>T) in the dystrophin gene causing total
      exon skipping and DMD phenotype.

PMID- 11241856
TI  - Subcommissural organ. Cellular, molecular, physiological, and pathological
      aspects: one hundred years of subcommissural organ research.

PMID- 11241857
TI  - Cell lineage of the subcommissural organ secretory ependymocytes: differentiating
      role of the environment.
AB  - SCO-ependymocytes have a secretory activity and a neural innervation relating
      them to neurosecretory nerve cells. To elucidate the cell lineage of the SCO
      ependymocytes and emphasize the role of the neural innervation in their
      differentiation, in particular 5-HT innervation, we analyzed the developmental
      pattern of expression of several glial and neuronal markers: (1) in the SCO of
      mammals possessing (rat, cat) or devoid (mouse, rabbit) of 5-HT innervation, (2)
      in rat 5-HT deafferented SCO, and (3) in rat SCO transplanted in a foreign
      environment, the fourth ventricle. The ability of SCO-ependymocytes to
      transiently express GFAP during development and express the glial alpha alpha
      enolase confirms the glial lineage of the SCO-ependymocytes. Synthesis of
      vimentin by SCO-ependymocytes relates them to the classical ependymocytes. The
      ability of mature SCO-ependymocytes to take up GABA only when they are innervated
      by 5-HT terminal underlines the role of the neural environment on the
      differentiation of these ependymocytes and suggests that differential maturation
      of the SCO according to its innervation, may lead to specific functional
      specialization of this organ in different species.

PMID- 11241858
TI  - Biosynthesis and molecular biology of the secretory proteins of the
      subcommissural organ.
AB  - Ependymal cells are specialized in the synthesis and release of different factors
      into the cerebrospinal fluid (CSF). The subcommissural organ (SCO) is one of the
      most active areas of the ventricular walls secreting into the CSF. This gland is
      localized in the roof of the third ventricle covering the posterior commissure.
      Glycoproteins synthesized in SCO cells are released into the ventricular CSF
      where they aggregate, in a highly ordered fashion, forming an elongated
      supramacromolecular structure known as the Reissner's fiber (RF). RF grows
      caudally and extends along the brain aqueduct, the fourth ventricle, and the
      whole length of the central canal of the spinal cord. The SCO cells synthesize
      glycoproteins of high molecular weight. A precursor form of 540 kDa is
      synthesized in bovine and chick SCO cells, and a transcript of 10--14 kb is
      expressed selectively in the bovine SCO cells. The processing of this molecule
      generates at least one protein of about 450 kDa (RF-Gly-I), which, after being
      released, is involved in the formation of RF. Additionally, biochemical data
      indicate that bovine SCO cells synthesize a second precursor compound of 320 kDa,
      which is also detected in rat, rabbit, and dog. We postulate that RF is formed by
      two different complexes, one of which has a very high molecular mass (700 kDa or
      more) and is made up of at least six polypeptides, with the polypeptide of 450
      kDa being its main component. The molecules that form RF in different species
      have different primary structures but they express common epitopes associated to
      the existence of cysteine bridges, which are probably crucial for polymerization
      of RF. Molecular procedures involving the use of anti-RF antibodies have led to
      the isolation of cDNA clones encoding two proteins known as RF-GLY-I and SCO
      spondin. In the last 3 years, five partial cDNA sequences encoding SCO-spondin
      like proteins have been obtained (Y08560, Y08561, AJ132107, AJ132106, AJ133488).
      These clones along with RF-GLY-I and SCO-spondin were computer-assembled
      generating a cDNA consensus sequence of 14.4 kb. Analyses of the long consensus
      sequence revealed an extended open reading frame (ORF-1) spanning from base 1,634
      to 14,400 that encodes for a putative protein of 4,256 amino acids (approximately
      450 kDa). The Mr of the predicted protein is consistent with the observed Mr of
      the largest protein recognized with anti-RF antibodies in SCO and RF extracts.
      However, the absence of consensus sequences typically present near the 5J'-end of
      the translation initiation site suggests the existence of a second open reading
      frame (ORF-2) extending from base 1 to base 14,400 in frame with the ORF-1 and
      probably encoding for the largest protein precursor (540 kDa). An antibody raised
      against a peptide sequence, deduced from the open reading frame encoded by a SCO
      cDNA, reacted specifically with the bovine and rat SCO-RF complex, thus
      indicating that the protein encoded by the cloned cDNA is part of RF. Immunoblots
      of bovine SCO extracts using the anti-peptide serum revealed bands of 540 kDa and
      450 kDa, but it did not react with the proteins of 320 and 190 kDa. These data
      support the existence of two precursors for the bovine RF-glycoproteins (540 and
      320 kDa) with the 450-kDa protein being a processed form of the 540-kDa
      precursor. We postulate that the cloned cDNAs encode for a protein that
      corresponds to the 540-kDa precursor and that at least part of this sequence is
      present in the processed form of 450 kDa that is secreted to form the RF.

PMID- 11241859
TI  - SCO-spondin, a glycoprotein of the subcommissural organ/Reissner's fiber complex:
      evidence of a potent activity on neuronal development in primary cell cultures.
AB  - In the cattle, SCO-spondin was shown to be a brain-secreted glycoprotein
      specifically expressed in the subcommissural organ (SCO), an ependymal
      differentiation located in the roof of the Sylvian aqueduct. Furthermore, SCO
      spondin makes part of Reissner's fiber (RF), a structure present in the central
      canal of the spinal cord. Sequencing of overlaping cDNA inserts after successive
      screening of a cattle SCO cDNA expression library allowed characterization of the
      complete sequence of this novel protein. Conserved domains were identified
      including twenty-six thrombospondin type 1 repeats (TSRs), nine low-density
      lipoprotein receptor LDLr type A domains (LDLRA), two epidermal growth factor EGF
      like domains, and homologies to mucins and the von Willebrand factor were found
      in the amino- and carboxy- termini. In addition, SCO-spondin shows a unique
      arrangement "in mosaic" of these domains. The putative function of SCO-spondin in
      neuronal differentiation is discussed regarding these features and homologies
      with other developmental molecules of the central nervous system exhibiting TSR
      domains, and involved in axonal guidance.To correlate molecular and functional
      features of SCO-spondin, we tested the effect of oligopeptides whose sequences
      include highly conserved regions of the TSRs, LDLRA repeats, and a potent site of
      attachment to glycosaminoglycan, on cortical and spinal cord neurons in primary
      cell cultures. Peptides corresponding to SCO-spondin TSRs markedly increased
      adhesivity and neuritic outgrowth of cortical neurons and induced disaggregation
      of spinal cord neurons. Thus, SCO-spondin is a candidate to interfere with
      neuronal development and/or axonal guidance during ontogenesis of the central
      nervous system in modulating side-to-side and side-to-substratum interactions,
      and in promoting neuritic outgrowth. RF proper has a wide range of activity on
      neuronal differentiation, including survival, aggregation, and disaggregation
      effects and neurite extension of cortical and spinal cord neurones "in vitro."
      Thus, the SCO/RF complex may interact with developmental processes of the central
      nervous system including the posterior commissure and spinal cord
      differentiation.

PMID- 11241860
TI  - Organ culture of the bovine subcommissural organ: evidence for synthesis and
      release of the secretory material.
AB  - The subcommissural organ (SCO) is a brain circumventricular organ formed by
      ependymal and hypendymal secretory cells. It secretes glycoproteins into the
      cerebrospinal fluid of the third ventricle where they condense into a thread-like
      structure known as Reissner's fiber (RF). The present study was designed to
      investigate whether or not the bovine SCO continues to synthesize and release
      glycoproteins after a long-term culture. Cultured explants of SCO survive for
      several months. The content of the secretory granules present in the cultured
      ependymocytes displayed immunoreactive and lectin-binding properties similar to
      those of the core glycosylated glycoproteins found in the bovine SCO. The
      explants actively incorporated (35)S-cysteine. In the cultured ependymocytes, the
      pattern of distribution of the radioactive label and that of the immunoreactive
      secretory material was similar, thus indicating that this material has been
      synthesized during culture. At the ultrastructural level, the cultured tissue
      exhibited a high degree of differentiation comparable to that of the bovine SCO
      in situ. A striking finding was the observation of similar results when
      cerebrospinal fluid was used as a culture medium. The addition of antibodies
      against RF-glycoproteins into the culture medium allowed visualization, by means
      of different immunocytochemistry protocols, deposits of extracellular
      immunoreactive secretory material on the free surface of the cultured
      ependymocytes, indicating that release of secretory glycoproteins into the
      culture medium does occur. Primary culture of dispersed SCO ependymocytes,
      obtained either from fresh or organ cultured bovine SCO, showed that these cells
      release RF-glycoproteins that aggregate in the vicinity of each cell. The present
      investigation has shown that: (1) two types of secretory ependymocytes become
      evident in the cultured SCO; (2) under culture conditions, the SCO cells increase
      their secretory activity; (3) explants of bovine SCO synthesize RF-glycoproteins
      and release them to the culture medium; (4) after release these proteins
      aggregate but do not form a RF; (5) a pulse of anti-RF antibodies into the
      culture medium blocks the secretion of RF-glycoproteins for several days.

PMID- 11241861
TI  - Analysis and quantification of the secretory products of the subcommissural organ
      by use of monoclonal antibodies.
AB  - Bovine Reissner's fiber (RF) glycoproteins were used as antigen for the
      production of polyclonal and monoclonal antibodies (Mabs). We also produced Mabs
      against intracellular secretory glycoproteins of the bovine subcommissural organ
      (SCO). These Mabs were used for immunodetection of secretory proteins in situ
      (structural and ultrastructural immunocytochemistry), in blots, and in solutions.
      Three different antigen-mediated ELISA were designed to evaluate the affinity of
      the Mabs, to study the nature of the epitopes, and for competition test among
      Mabs. Two double antibody sandwich ELISA were designed to detect and quantify
      soluble secretory materials in different samples, to study coexistence of
      epitopes, and to elucidate whether epitopes for Mabs are repeated or not in the
      RF-glycoproteins. Twenty-three Mabs recognizing the bovine RF- and SCO
      glycoproteins in solutions (ELISA) as well as in tissue sections, were obtained.
      Nineteen of these Mabs also recognized the pig SCO, 11 the rabbit SCO, 6 the dog
      SCO, and 5 the rat SCO. None of the Mabs recognized the SCO of non-mammalian
      species. The different types of ELISA demonstrated that: (1) the epitopes reside
      in the proteinaceous moiety of the secretion, (2) they coexist in the same
      molecular forms and, with few exceptions, they did not overlap, (3) they were not
      repeated in the secretory molecule(s). Three Mabs were used for immunoblotting of
      RF; one of them revealed the same band pattern as that shown by an anti-RF serum.
      It is concluded that all Mabs raised in our laboratory are directed against non
      repeated sequences of RF-glycoproteins that have not been conserved in vertebrate
      phylogeny.

PMID- 11241862
TI  - Neural input and neural control of the subcommissural organ.
AB  - The neural control of the subcommissural organ (SCO) has been partially
      characterized. The best known input is an important serotonergic innervation in
      the SCO of several mammals. In the rat, this innervation comes from raphe nuclei
      and appears to exert an inhibitory effect on the SCO activity. A GABAergic
      innervation has also been shown in the SCO of the rat and frog Rana perezi. In
      the rat, GABA and the enzyme glutamate decarboxylase are involved in the SCO
      innervation. GABA is taken up by some secretory ependymocytes and nerve
      terminals, coexisting with serotonin in a population of synaptic terminals.
      Dopamine, noradrenaline, and different neuropeptides such as LH-RH, vasopressin,
      vasotocin, oxytocin, mesotocin, substance P, alpha-neoendorphin, and galanin are
      also involved in SCO innervation. In the bovine SCO, an important number of
      fibers containing tyrosine hydroxylase are present, indicating that in this
      species dopamine and/or noradrenaline-containing fibers are an important neural
      input. In Rana perezi, a GABAergic innervation of pineal origin could explain the
      influence of light on the SCO secretory activity in frogs. A general conclusion
      is that the SCO cells receive neural inputs from different neurotransmitter
      systems. In addition, the possibility that neurotransmitters and neuropeptides
      present in the cerebrospinal fluid may also affect the SCO activity, is
      discussed.

PMID- 11241863
TI  - Presence and functional significance of neuropeptide and neurotransmitter
      receptors in subcommissural organ cells.
AB  - The subcommissural organ (SCO) of mammals is innervated by several neuropeptide
      and neurotransmitter systems. So far, substance P (SP), oxytocin (OXT),
      vasopressin (VP), somatostatin (SOM), thyrotropin-releasing factor (TRF), and
      angiotensin II (ANGII) were identified in neuropeptidergic input systems, and
      serotonin (5HT), gamma-amino butyric acid (GABA), noradrenaline (NA), dopamine
      (DA), and acetylcholine (Ach) were neurotransmitters observed in systems afferent
      to the SCO. In the present report, based on literature data and our own
      investigations, we describe the occurrence of peptide and transmitter receptors
      in the SCO by means of autoradiographic and biochemical studies. Further, we
      summarize aspects of the signal transduction cascades possibly linked to
      different receptor types of the SCO; these studies included the use of calcium
      imaging (FURA-2 technique), ELISA technique, and immunocytochemistry. Receptors
      were identified for adenosine, angiotensin II, imidazoline, glucocorticoids,
      mineralocorticoids, NA, and embryonic brain kinase. The studies on intracellular
      signal-transduction indicated receptors for tachykinins and for ATP. In SCO
      cells, Ca(++) and c-AMP were identified to act as second messengers. As important
      transcription factor, cAMP-/Ca(++)-response element binding protein (CREB) was
      observed. Ach and NA did not show a significant effect on the subcommissural
      signal transduction.

PMID- 11241864
TI  - Searching for specific binding sites of the secretory glycoproteins of the
      subcommissural organ.
AB  - The molecular organization of Reissner's fiber (RF), the structure of its
      proteins, and the permanent turnover of these proteins are all facts supporting
      the possibility that RF may perform multiple functions. There is evidence that
      CSF-soluble RF-glycoproteins may occur under physiological conditions. The
      present investigation was designed to investigate the probable existence within
      the CNS of specific binding sites for RF-glycoproteins. Three experimental
      protocols were used: (1) immunocytochemistry of the CNS of bovine fetuses using
      anti-idiotypic antibodies, raised against monoclonal antibodies developed against
      bovine RF-glycoproteins; (2) in vivo binding of the RF glycoproteins, perfusing
      into the rat CSF 125I-labeled RF-glycoproteins, or grafting SCO into a lateral
      ventricle of the rat; (3) in vitro binding of unlabeled RF-glycoproteins to rat
      and bovine choroid plexuses maintained in culture. One of the anti-idiotypic
      antibody generated by a Mab raised against RF-glycoproteins binds to choroidal
      cells. Furthermore, binding of RF-glycoproteins to the rat choroid plexus was
      obtained when: (1) the choroid plexus was cultured in the presence of unlabeled
      RF-glycoproteins; (2) the concentration of soluble RF-glycoproteins in the CSF
      was increased by isografting SCOs into a lateral ventricle; (3) radiolabeled
      glycoproteins were perfused into the ventricular CSF. This evidence suggests that
      the apical plasma membrane of the ependymal cells of the choroid plexus has
      specific binding sites for RF-glycoproteins, of unknown functional significance.
      The radiolabeled RF-glycoproteins perfused into the rat CSF also bound to the
      paraventricular thalamic nucleus, the floor of the Sylvian aqueduct and of the
      rostral half of the fourth ventricle, and the meninges of the brain and spinal
      cord. The labeling of the paraventricular thalamic nucleus points to a functional
      relationship between this nucleus and the SCO. The possibility that the SCO may
      be a component of the circadian timing system is discussed.

PMID- 11241865
TI  - Spatial distribution of Reissner's fiber glycoproteins in the filum terminale of
      the rat and rabbit.
AB  - The subcommissural organ secretes into the third ventricle glycoproteins that
      condense to form the Reissner's fiber (RF). At the distal end of the central
      canal of the spinal cord, the RF-glycoproteins accumulate in the form of an
      irregular mass known as massa caudalis. Antibodies against RF-glycoproteins and a
      set of lectins were used at the light and electron microscopic level to
      investigate the spatial distribution of the massa caudalis material in the rat
      and rabbit filum terminale. In the sacral region of the rat, the central canal
      presents gaps between the ependymal cells through which RF-glycoproteins spread
      out. The bulk of massa caudalis material, however, escapes through openings in
      the dorsal wall of the terminal ventricle. In the rabbit, the massa caudalis is
      formed within the ependymal canal, at the level of the second coccygeal vertebra,
      it accumulates within preterminal and terminal dilatations of the central canal,
      and it escapes out through gaps in the dorsal ependymal wall of the terminal
      ventricle. The existence of wide intercellular spaces and a large orifice
      (neuroporous) in the dorsal ependymal wall of the terminal ventricle, and the
      passage of RF-material through them, appear to be conserved evolutionary
      features. After leaving the terminal ventricle of the rat and rabbit, RF
      glycoproteins establish a close spatial association with the numerous blood
      vessels irrigating the filum terminale, suggesting that in these species the
      blood vessels are the site of destination of the RF-glycoproteins escaping from
      the central canal, thus resembling the situation found in lower vertebrates. When
      passing from the RF stage to the massa caudalis stage, the rabbit RF
      glycoproteins lose their sialic acid residues, exposing galactose as the terminal
      residue. Since this sialic acid-galactose modification of RF-glycoproteins had
      also been described in lamprey larvae, it may be regarded as a conserved
      evolutionary feature associated with the formation of the massa caudalis.

PMID- 11241866
TI  - Functional aspects of the subcommissural organ-Reissner's fiber complex with
      emphasis in the clearance of brain monoamines.
AB  - Reissner's fiber (RF) extends along the cerebral aqueduct, fourth ventricle, and
      the entire length of the central canal of the spinal cord. It grows continuously
      in the caudal direction by addition of newly released glycoproteins by the
      subcommissural organ (SCO) to its proximal end. Several hypotheses about RF
      function have been advanced. One of them postulates that RF binds biogenic amines
      present in the CSF and clears them away. In recent years, this hypothesis has
      been tested in our laboratory by using several experimental protocols. Firstly,
      the CSF concentration of monoamines was investigated in RF-deprived rats
      subjected to immunological neutralization of the SCO-RF complex. Secondly, the
      capacity of RF to bind monoamines in vivo was studied by injecting radiolabeled
      serotonin or noradrenaline into the rat CSF, and by perfusing them into the CSF,
      during one week, using an Alzet's osmotic pump. In vitro binding studies were
      performed using isolated bovine RF. All the findings obtained indicate that RF
      binds monoamines present in the ventricular CSF and then transports them along
      the central canal. In the absence of RF, the CSF concentration of monoamines
      increases sharply.

PMID- 11241867
TI  - Human subcommissural organ, with particular emphasis on its secretory activity
      during the fetal life.
AB  - The subcommissural organ (SCO) is a conserved brain gland present throughout the
      vertebrate phylum. During ontogeny, it is the first secretory structure of the
      brain to differentiate. In the human, the SCO can be morphologically
      distinguished in 7- to 8-week-old embryos. The SCO of 3- to 5-month-old fetuses
      is an active, secretory structure of the brain. However, already in 9-month-old
      fetuses, the regressive development of the SCO-parenchyma is evident. In 1-year
      old infants, the height of the secretory ependymal cells is distinctly reduced
      and they are grouped in the form of islets that alternate with cuboid non
      secretory ependyma. The regression of the SCO continues during childhood, so that
      at the ninth year of life the specific secretory parenchyma is confined to a few
      islets of secretory ependymal cells. The human fetal SCO shares the distinct
      ultrastructural features characterizing the SCO of all other species, namely, a
      well-developed rough endoplasmic reticulum, with many of its cisternae being
      dilated and filled with a filamentous material, several Golgi complexes, and
      secretory granules of variable size, shape, and electron density. The human fetal
      SCO does not immunoreact with any of the numerous polyclonal and monoclonal
      antibodies raised against RF-glycoproteins of animal origin. This and the absence
      of RF in the human led to the conclusion that the human SCO does not secrete RF
      glycoproteins. Taking into account the ultrastructural, lectin-histochemical, and
      immunocytochemical findings, it can be concluded that the human SCO, and most
      likely the SCO of the anthropoid apes, secrete glyco- protein(s) with a protein
      backbone of unknown nature, and with a carbohydrate chain similar or identical to
      that of RF-glycoproteins secreted by the SCO of all other species. These, as yet
      unidentified, glycoprotein(s) do not aggregate but become soluble in the CSF.
      Evidence is presented that these CSF-soluble proteins secreted by the human SCO
      correspond to (1) a 45-kDa compound similar or identical to transthyretin and,
      (2) a protein of about 500 kDa.

PMID- 11241868
TI  - Subcommissural organ, cerebrospinal fluid circulation, and hydrocephalus.
AB  - Under normal physiological conditions the cerebrospinal fluid (CSF) is secreted
      continuously, although this secretion undergoes circadian variations. Mechanisms
      operating at the vascular side of the choroidal cells involve a sympathetic and a
      cholinergic innervation, with the former inhibiting and the latter stimulating
      CSF secretion. There are also regulatory mechanisms operating at the ventricular
      side of the choroidal cells, where receptors for monoamines such as dopamine,
      serotonin, and melatonin, and for neuropeptides such as vasopressin, atrial
      natriuretic hormone, and angiotensin II, have been identified. These compounds,
      that are normally present in the CSF, participate in the regulation of CSF
      secretion. Although the mechanisms responsible for the CSF circulation are not
      fully understood, several factors are known to play a role. There is evidence
      that the subcommissural organ (SCO)--Reissner's fiber (RF) complex is one of the
      factors involved in the CSF circulation. In mammals, the predominant route of
      escape of CSF into blood is through the arachnoid villi. In lower vertebrates,
      the dilatation of the distal end of the central canal, known as terminal
      ventricle or ampulla caudalis, represents the main site of CSF escape into blood.
      Both the function and the ultrastructural arrangement of the ampulla caudalis
      suggest that it may be the ancestor structure of the mammalian arachnoid villi.
      RF-glycoproteins reaching the ampulla caudalis might play a role in the formation
      and maintenance of the route communicating the CSF and blood compartments. The
      SCO-RF complex may participate, under physiological conditions, in the
      circulation and reabsorption of CSF. Under pathological conditions, the SCO
      appears to be involved in the pathogeneses of congenital hydrocephalus. Changes
      in the SCO have been described in all species developing congenital
      hydrocephalus. In these reports, the important question whether the changes
      occurring in the SCO precede hydrocephalus, or are a consequence of the
      hydrocephalic state, has not been clarified. Recently, evidence has been obtained
      indicating that a primary defect of the SCO-RF complex may lead to hydrocephalus.
      Thus, a primary and selective immunoneutralization of the SCO-RF complex during
      the fetal and early postnatal life leads to absence of RF, aqueductal stenosis,
      increased CSF concentration of monoamines, and a moderate but sustained
      hydrocephalus.

PMID- 11241869
TI  - Vertebrate floor plate transiently expresses a compound recognized by antisera
      raised against subcommissural organ secretion.
AB  - Located along the ventral midline of the neural tube, the floor plate (FP)
      performs an essential role in central nervous system development, especially in
      the patterning of the ventral region of the neural tube and axonal guidance.
      Several studies have been directed to the identification of molecules mediating
      some of the functions of the FP. Most of the models proposed for floor plate
      actions involve contact-mediated- and/or gradients of diffusible-signals acting
      throughout the nervous tissue. This report presents and discusses findings
      showing that the FP cells secrete a novel compound, which is recognized by
      antisera raised against secretory products of the subcommissural organ (SCO).
      This immunoreactive compound appears to be very similar to one of the
      glycoproteins secreted by the SCO. This immunoreactivity is expressed transiently
      during central nervous system development, and its rostro-caudal extension along
      the anterior-posterior axis of the FP displays some species variations. However,
      a constant feature in all species investigated is that this immunoreactive
      compound is highly expressed in the FP located in the mesencephalic-metencephalic
      boundary. The distribution of this compound is compatible with basal and apical
      pathways of release from FP cells. The former might participate in the formation
      of some brain commissures. The latter might involve the use of the cerebrospinal
      fluid as a route for performing actions on distant targets, a pathway somehow
      disregarded by most models accounting for morphogen actions.

PMID- 11241870
TI  - Hindbrain floor plate of the rat: ultrastructural changes occurring during
      development.
AB  - Most of the molecular and experimental studies on the floor plate (FP) have been
      performed on the FP region extending along the spinal cord. However, little is
      known about the hindbrain FP. The FP undergoes regional and temporal changes
      throughout development, but information with respect to the ultrastructural
      correlate of such changes is missing. The present investigation was focused on
      the ultrastructural developmental changes occurring in the FP of the rat
      hindbrain. The FP cells of the hindbrain secrete a material reacting with
      antibodies against the secretory glycoproteins of the subcommissural organ
      (AFRU). This antibody was used to perform an ultrastructural immunocytochemical
      analysis of the rat FP. From E-12 on, there is a progressive increase in the
      development of the rough endoplasmic reticulum (RER), so that by E-18, it has
      reached a high degree of hypertrophy. A unique feature of the hindbrain FP cells
      is the presence of tubular formations and 140-nm vesicles that appear to
      originate from RER cisternae. The labelling of these two structures with AFRU and
      Concanavalin A strongly suggests that they are pre-Golgi compartments containing
      secretory material. Since these structures are present in the basal process and
      in the apical cell pole of the FP cells, the possibility that they release their
      content at these sites, is discussed. It is proposed that a secretory mechanism
      bypassing the Golgi apparatus (constitutive secretion?) operates in the FP cells.
      The presence of apoptotic cells within the FP of E-20 embryos and newborns
      suggests that death, and not re-differentiation, is the fate of the FP cells.

PMID- 11241871
TI  - Time courses of left and right amygdalar responses to fearful facial expressions.
AB  - Despite the many studies highlighting the role of the amygdala in fear
      perception, few have examined differences between right and left amygdalar
      responses. Using functional magnetic resonance imaging (fMRI), we examined neural
      responses in three groups of healthy volunteers (n = 18) to alternating blocks of
      fearful and neutral faces. Initial observation of extracted time series of both
      amygdalae to these stimuli indicated more rapid decreases of right than left
      amygdalar responses to fearful faces, and increasing magnitudes of right
      amygdalar responses to neutral faces with time. We compared right and left
      responses statistically by modeling each time series with (1) a stationary fit
      model (assuming a constant magnitude of amygdalar response to consecutive blocks
      of fearful faces) and (2) an adaptive model (no assumptions). Areas of
      significant sustained nonstationarity (time series points with significantly
      greater adaptive than stationary model fits) were demonstrated for both
      amygdalae. There was more significant nonstationarity of right than left
      amygdalar responses to neutral, and left than right amygdalar responses to
      fearful faces. These findings indicate significant variability over time of both
      right and left amygdalar responses to fearful and neutral facial expressions and
      are the first demonstration of specific differences in time courses of right and
      left amygdalar responses to these stimuli.

PMID- 11241872
TI  - Integrated volume visualization of functional image data and anatomical surfaces
      using normal fusion.
AB  - A generic method, called normal fusion, for integrated three-dimensional (3D)
      visualization of functional data with surfaces extracted from anatomical image
      data is described. The first part of the normal fusion method derives
      quantitative values from functional input data by sampling the latter along a
      path determined by the (inward) normal of a surface extracted from anatomical
      data; the functional information is thereby projected onto the anatomical surface
      independently of the viewpoint. Fusion of the anatomical and functional
      information is then performed with a color-encoding scheme based on the HSV
      model. This model is preferred over the RGB model to allow easy, rapid, and
      intuitive retrospective manipulation of the color encoding of the functional
      information in the integrated display, and two possible strategies for this
      manipulation are explained. The results first show several clinical examples that
      are used to demonstrate the viability of the normal fusion method. These same
      examples are then used to evaluate the two HSV color manipulation strategies.
      Furthermore, five nuclear medicine physicians used several other clinical cases
      to evaluate the overall approach for manipulation of the color encoded functional
      contribution to an integrated 3D visualization. The integrated display using the
      normal fusion technique combined with the added functionality provided by the
      retrospective color manipulation was highly appreciated by the clinicians and can
      be considered an important asset in the investigation of data from multiple
      modalities.

PMID- 11241873
TI  - Neural basis of novel and well-learned recognition memory in schizophrenia: a
      positron emission tomography study.
AB  - The level of familiarity of a given stimulus plays an important role in memory
      processing. Indeed, the novelty/familiarity of learned material has been proven
      to affect the pattern of activations during recognition memory tasks. We used
      visually presented words to investigate the neural basis of recognition memory
      for relatively novel and familiar stimuli in schizophrenia. Subjects were 34
      healthy volunteers and 19 schizophrenia spectrum patients. Two experimental
      cognitive conditions were used: 1 week and again 1 day prior to the PET imaging
      subjects had to thoroughly learn a list of 18 words (well-learned memory).
      Subjects were also asked to learn another set of 18 words presented 1 min before
      the PET experiment (novel memory). During the PET session, subjects had to
      recognize the list of 18 words among 22 new (distractor) words. Subjects also
      performed a control task (reading words). A nonparametric randomization test and
      a statistical t-mapping method were used to determine between- and within-group
      differences. In patients the recognition of novel material produced relatively
      less flow in several frontal areas, superior temporal gyrus, insular cortex, and
      parahippocampal areas, and relatively higher activity in parietal areas, visual
      cortex, and cerebellum, compared to controls. No significant differences in flow
      were seen when comparing well-learned memory activations between groups. These
      results suggest that different neural pathways are engaged during novel
      recognition memory in patients with schizophrenia compared to healthy
      individuals. During recognition of novel material, patients failed to activate
      frontal/limbic regions, recruiting a set of posterior perceptual brain regions
      instead.

PMID- 11241874
TI  - Automated measurement of latent morphological features in the human corpus
      callosum.
AB  - Our objective was to develop a novel factor-based analysis of the morphology of
      the corpus callosum and assess its applicability to the study of normal
      development, intelligence, and other subject characteristics. The contour of the
      corpus callosum was defined in the midsagittal planes of the MRI scans of 325
      subjects, 6 to 88 years of age. The contours were coregistered, rescaled, and
      resampled to 50 points that were then entered into a principal components
      analysis with varimax rotation. The analysis yielded 8 factors for the contours
      of 138 healthy subjects. A second analysis of contours from 187 subjects in a
      patient group extracted 8 similar factors. Correlations of factor scores with
      conventional measures of callosum shape supported the construct validity of the
      assignment of morphological features to each of the factors. Correlations of
      factor scores with age, sex, handedness, ventricular volume, and IQ demonstrated
      the predictive validity of the factor structure and helped to define the neural
      correlates of these subject characteristics. We conclude that factor-based
      measures capture latent morphological features of the corpus callosum that are
      reliable and valid. Future studies will determine whether these novel measures
      are more closely related to neurobiologically important features of the corpus
      than are conventional measures of callosum size and shape.

PMID- 11241875
TI  - Cortical effects of bromocriptine, a D-2 dopamine receptor agonist, in human
      subjects, revealed by fMRI.
AB  - Studies of human subjects performing cognitive tasks on and off dopaminergic
      drugs have suggested a specific role of dopamine in cognitive processes,
      particularly in working memory and prefrontal "executive" functions. However, the
      cortical effects of these drugs have been poorly understood. We used functional
      magnetic resonance imaging (fMRI) to examine both task-specific and general
      changes in cortical activity associated with bromocriptine, a selective agonist
      for D-2 dopamine receptors. Bromocriptine resulted in task-specific modulations
      of task-related activity in three cognitive tasks. Across tasks, the overall
      effect of the drug was to reduce task-related activity. We also observed drug
      effects on behavior that correlated with individual differences in memory span.
      We argue that bromocriptine may show both task-specific modulation and task
      general inhibition of neural activity due to dopaminergic neurotransmission.

PMID- 11241877
TI  - Self-injurious behavior: gene-brain-behavior relationships.
AB  - This paper summarizes a conference held at the National Institute of Child Health
      and Human Development on December 6-7, 1999, on self-injurious behavior [SIB] in
      developmental disabilities. Twenty-six of the top researchers in the U.S. from
      this field representing 13 different disciplines discussed environmental
      mechanisms, epidemiology, behavioral and pharmacological intervention strategies,
      neurochemical substrates, genetic syndromes in which SIB is a prominent
      behavioral phenotype, neurobiological and neurodevelopmental factors affecting
      SIB in humans as well as a variety of animal models of SIB. Findings over the
      last decade, especially new discoveries since 1995, were emphasized. SIB is a
      rapidly growing area of scientific interest to both basic and applied
      researchers. In many respects it is a model for the study of gene-brain-behavior
      relationships in developmental disabilities.

PMID- 11241878
TI  - Specific reading disability: a multiplanar view.
AB  - In the past three decades a revolution has altered the way society approaches
      people with disabilities. Social changes resulted in a significant increase in
      fundamental and applied research that seeks to improve the lives of people with
      disabilities by facilitating better understanding of the mechanisms,
      manifestations, prevention, and treatment of functional impairment. Specific
      Reading Disability (SRD) has benefited from this revolution. This review focuses
      on the evolution of SRD, new information in its neurobiology and management, and
      the challenges that remain. Evidence from a wide spectrum of research provides
      strong support for the role of phonology in Specific Reading Disability. Despite
      the mounting evidence, the case is far from completely established. Adults with
      compensated SRD read but still demonstrate disordered phonology (Felton et al.
      [1990] Brain Language 39:485-497). Whether poor phonology is causal or a
      covariant remains to be demonstrated. Of children with poor phonology, it is not
      known how many are poor readers. While phonology is associated with SRD, other
      studies have questioned the uniqueness of SRD. Challenges have been made to the
      method of classification, the uniqueness of phonological dysfunction as a
      mechanism in SRD and the response to treatment. In the final analysis all poor
      readers may have a common core of dysphonology, independent of whether their
      reading is discrepant from their IQ.

PMID- 11241879
TI  - Current directions in research on autism.
AB  - One of the most active areas of current research in the field of developmental
      disorders is autism. Since the NIH State of the Science conference, held in 1995
      (Bristol et al. [1996] J. Autism Dev. Disorders 26:121-154), funding
      opportunities for comprehensive research programs addressing genetic,
      neurobiological, and behavioral aspects of this complex disorder have grown
      exponentially. Although we are far from having a complete understanding of the
      causes and deficits that define autism, significant progress has been made over
      the past few years. In this review, we summarize recent developments across a
      number of different areas of research in the field of autism, including
      diagnosis; defining the phenotypic features in individuals with autism; genetic
      bases; and neurobiological deficits.

PMID- 11241880
TI  - Advances in prevention and treatment of cerebral palsy.
AB  - In recent years there have been a number of advances in understanding of
      predisposing and protective factors in the development of cerebral palsy in
      infants. Multiple gestation births, maternal infection, and maternal and fetal
      thrombophilic conditions all predispose to the development of CP in the infant.
      Opportunities for prevention of CP may develop from an improved understanding of
      these factors and their mechanisms of operation. Similar progress has been made
      in the evaluation of treatments for CP and the effects of these treatments on the
      individual's impairment, function, and disability. Selective posterior rhizotomy
      and Botulinum toxin A are now widely used in the treatment of spasticity. The
      challenge remains to determine how effectively these promising interventions can
      alter long-term function and quality of life outcomes in children and adults with
      CP.

PMID- 11241881
TI  - Down syndrome: progress in research.
AB  - This review discusses the research published in the last five years on the
      behavioral, genetic, medical, and neuroscience aspects of Down syndrome. The
      subject areas that have experienced the most active research include Alzheimer
      disease, language development, leukemia, and pregnancy screening and diagnosis.
      These and other areas are reviewed.

PMID- 11241882
TI  - Theoretical perspectives on language and communication problems in mental
      retardation and developmental disabilities.
AB  - We argue that researchers interested in language and communication problems in
      mental retardation or any other developmental disorder should view such problems
      as emerging within the broader context of the behavioral profile, or phenotype,
      associated with a particular genetic condition. This will require understanding
      the direct and indirect effects of genes on the development of language and
      communication and thereby an understanding of the complex relations that exist
      between language and other dimensions of psychological and behavioral functioning
      as well as an understanding of the environments in which the developing person
      acts and is acted upon. We believe that the dominant model for understanding
      language and communication problems--the nativist approach, which emphasizes the
      child's innate capacity for acquiring language and characterizes language as
      consisting of a set of context-free deterministic rules that operate on abstract
      representations--is inconsistent with an emphasis on indirect genetic effects. We
      review recent evidence that undermines the nativist approach--evidence concerning
      the initial state of the language-learning child, the role of environmental
      input, the competence-performance distinction, and modularity. In place of
      nativism, we argue for Emergentism, which is a model in which language is seen to
      emerge from the interaction between the child's biological abilities to map
      statistical properties of the language input into a distributed representation
      and the characteristics of the language learning environment and for the purpose
      of engaging in real-time, meaningful language use.

PMID- 11241883
TI  - Perinatal brain injury: from pathogenesis to neuroprotection.
AB  - Brain injury secondary to hypoxic-ischemic disease is the predominant form of all
      brain injury encountered in the perinatal period. The focus of this article is
      the most recent research developments in this field and especially those
      developments that should lead to the most profound effects on interventions in
      the first years of the new millennium. Neuronal injury is the predominant form of
      cellular injury in the term infant. The principal mechanisms leading to neuronal
      death after hypoxia-ischemia/reperfusion are initiated by energy depletion,
      accumulation of extracellular glutamate, and activation of glutamate receptors.
      The cascade of events that follows involves accumulation of cytosolic calcium and
      activation of a variety of calcium-mediated deleterious events. Notably this
      deleterious cascade, which evolves over many hours, may be interrupted even if
      interventions are instituted after termination of the insult, an important
      clinical point. Of the potential interventions, the leading candidates for
      application to the human infant in the relative short-term are mild hypothermia,
      inhibitors of free radical production, and free radical scavengers. Promising
      clinical data are available for the use of mild hypothermia.

PMID- 11241884
TI  - Prospects for prenatal gene therapy in disorders causing mental retardation.
AB  - Advances in understanding the genetics and pathogenesis of disease and in
      prenatal diagnosis have lead to an exploration of ways to intervene earlier and
      earlier in the disease process. The possibility of prenatal gene therapy for
      severe genetic and developmental disorders has sparked new research and debate as
      to its feasibility, reliability, and ethics as a therapeutic option. Recent
      animal studies have demonstrated the feasibility of introducing a vector into the
      developing fetus. The optimal timing and best mode of delivery, however, have yet
      to be defined. Whether or not this research should be pursued also has been the
      subject of recent bioethical debates. There is additional concern with the
      possibility of in utero gene transfer inducing mutagenesis and subsequent tumor
      formation. This review will provide a summary of the current state of knowledge
      in the field of prenatal gene therapy and possible directions for the future
      research.

PMID- 11241886
TI  - Genetic susceptibility factors of Type 1 diabetes in Asians.
AB  - Type 1 diabetes is a multifactorial disease in which the insulin producing beta
      cells of the pancreas are destroyed by the immune system, a process determined by
      the activity of major histocompatibility complex (MHC)-restricted T lymphocytes.
      Progress has been made in elucidating genetic factors involved in Type 1 diabetes
      in Caucasians, with less data available from Asia. For Asians, the human MHC
      locus (HLA region), especially the class II region, is the major susceptibility
      interval. The role of IDDM2, the insulin locus, has been questioned in Asia. In
      contrast to Caucasians, Asian populations have a very low incidence of Type 1
      diabetes (0.4-1.1 cases/year/100 000 individuals). This low incidence rate in the
      Asian population may be related to the population frequency distribution of
      susceptible Type 1 diabetes genes, especially of HLA. The overall risk for Type 1
      diabetes from HLA DR and DQ is determined by polymorphic residues (alleles) and
      particular combinations of alleles (haplotypes and genotypes) in a given
      individual. In Asians, it is very common that a protective DR4 allele is
      associated with susceptible DQ alleles while neutral/protective DQ alleles are
      associated with the susceptible DR4 alleles. Our analyses indicate that the
      counterbalancing between susceptible DRB1 and protective DQB1, and vice versa, is
      a factor that may contribute to the low incidence of diabetes in Asians. We find
      that identical HLA DRB1-DQB1 haplotypes of Asians and Caucasians have similar
      transmission to diabetic children and similar associations with diabetes.
      Moreover, the association with diabetes and transmission to a diabetic offspring
      of DR4 haplotypes varies depending on the haplotype borne on the homologous
      chromosome. This might contribute not only to the synergistic effect of DR3/4,
      but also to the susceptibility influence of DQB1*0401 haplotypes confined to
      DR4/X. High-risk DR4 subtypes were predominant in DR4/X, whereas protective DR4
      subtypes were observed mainly in the DR3/4 genotype. Since in Asians DQB1*0401 is
      in linkage disequilibrium (LD) with DRB1*0405, we find more DRB1*0405-DQB1*0401
      haplotypes in patients with DR4/X than in patients with DR3/4, suggesting that
      the contribution of the DRB1 locus may be greater in DR4/X than in DR3/4
      genotypes. Several genome scans suggested additional susceptibility intervals and
      provided supporting evidence for several previously reported linkages. Other
      studies focused on the confirmation of linkage using multipoint sib-pair analyses
      with densely spaced markers and multiethnic collection of families. Although
      significant and consistent linkage evidence was reported for the susceptibility
      intervals IDDM12 (on 2q33) even in Asia, evidence for most other intervals varies
      in different data sets. LD mapping has become an increasingly important tool for
      both confirmation and fine-mapping of susceptibility intervals, as well as
      identification of etiological mutations. The examination of large and ethnically
      varied data sets including those of Asia has allowed identification of haplotypes
      that differ only at a single codon in a single locus. As more data become
      available, the study of pairs of haplotypes which differ at a single polymorphic
      site, but have different effects on disease susceptibility, should allow more
      precise definition of the polymorphisms involved in the disease process.

PMID- 11241887
TI  - Visual electrophysiological responses in persons with type 1 diabetes.
AB  - Persons with type 1 diabetes show electrophysiological abnormalities of the
      visual system which are revealed by methods such as flash electroretinogram
      (FERG), oscillatory potentials (OPs), pattern electroretinogram (PERG), focal
      electroretinogram (focal ERG), visual evoked potentials (VEP) in basal condition
      and after photostress. This review reports the changes in electrophysiological
      responses of the different structures composing the visual system observed in
      persons with type 1 diabetes before the development of the overt clinical
      retinopathy. In persons with type 1 diabetes without retinopathy (IDD), the
      earlier abnormal electrophysiological responses are recorded from the innermost
      retinal layers and postretinal visual pathways, as suggested by impaired PERGs
      and delayed retinocortical time (RCT). These are observed in IDD persons with a
      disease duration shorter than 6 months. Further electrophysiological changes are
      recorded from the macula (abnormal focal ERG and VEP after photostress) in IDD
      persons with disease duration greater than 1 year. Additional
      electrophysiological changes are recorded from the middle and outer retinal
      layers (impaired FERG and OPs) in IDD persons with a disease duration greater
      than 10 years. All the electrophysiological tests show a greater degree of
      abnormal responses in persons with type 1 diabetes when a background retinopathy
      is present.

PMID- 11241888
TI  - Age-related insulin resistance: is it an obligatory finding? The lesson from
      healthy centenarians.
AB  - It is widely known that advancing age is associated with impaired glucose
      handling. A unifying hypothesis explaining the relationship between aging and
      insulin resistance might encompass four main pathways, namely: (a) anthropometric
      changes (relative and absolute increase in body fat combined with a decline in
      fat free mass) which could be the anatomic substrate for explaining the reduction
      in active metabolic tissue; (b) environmental causes, mainly diet style and
      physical activity; (c) neuro-hormonal variations [decline in plasma
      dehydroepandrosterone sulphate (DHEAS) and IGF-1]; and finally (d) the rise in
      oxidative stress. Indeed previous studies have also investigated the occurrence
      and the degree of insulin resistance in healthy centenarians. Such data
      demonstrated that age-related insulin resistance is not an obligatory finding in
      the elderly and that healthy centenarians have a preserved insulin action
      compared to aged subjects. Why insulin action is preserved in centenarians is
      still not known. Nevertheless, a possible approach to the question is to outline
      the centenarians' anthropometric, endocrine and metabolic characteristics in
      order to design a clinical picture of such metabolic "successful aging".
      According to the remodeling theory of age, the preserved insulin action in
      centenarians might be the net result of the continuous adaptation of the body to
      the deleterious changes that occur over time. Nevertheless, only future
      longitudinal studies specifically designed to investigate the relationship
      between extreme old age and degree of insulin sensitivity will provide a
      conclusive answer with regard to the pathophysiology of adaptive metabolic
      changes occurring in the elderly.

PMID- 11241889
TI  - Abnormalities in apo B-containing lipoproteins in diabetes and atherosclerosis.
AB  - Atherosclerosis is the major cause of death in patients with diabetes. Low
      density lipoprotein (LDL) being the most important cholesterol-carrying
      lipoprotein has been studied extensively in both diabetes and non-diabetes. This
      paper reviews the literature but also focuses on the precursors of LDL and in
      particular the postprandial apo B-containing lipoproteins. Abnormalities in the
      postprandial lipoproteins and alteration in chylomicron assembly and clearance
      are discussed and the evidence presented suggesting the importance of
      dysregulation of these lipoproteins in atherosclerotic progression. The
      relationship between chylomicron production in the intestine and hepatic release
      of very low-density lipoproteins (VLDL) is explored, as is the interrelationship
      between clearance rates of these lipoproteins. The size of LDL influences its
      atherogenicity. VLDL composition and size in relation to its influence on LDL is
      discussed. The effect of diet on the composition of lipoproteins and the
      relationship between fatty acid composition and clearance is reviewed. Evidence
      that diabetic control beneficially alters lipoprotein composition is presented
      suggesting how improved diabetic control may reduce atherosclerosis. The review
      concludes with a discussion on the effect of the apo B-containing lipoproteins
      and their modification through glycation and oxidation on macrophage and
      endothelial function.

PMID- 11241891
TI  - Bovine beta-casein antibodies in breast- and bottle-fed infants: their relevance
      in Type 1 diabetes.
AB  - BACKGROUND: Bovine beta-casein is a cow's milk protein that targets both humoral
      and cellular immune responses in patients with Type 1 diabetes and, to a lesser
      degree, also in normal subjects. In this study we aimed to determine whether the
      avoidance of cow's milk consumption early in life could prevent the development
      of antibody response to bovine beta-casein despite the mother being exposed on a
      daily basis to cow's milk consumption. MATERIALS AND METHODS: We measured the
      antibody response to bovine beta-casein using an ELISA method in 28 healthy
      infants under 4 months of age, of whom 16 were exclusively breast-fed and 12 were
      bottle-fed with cow's milk. In addition, beta-casein antibodies were measured in
      37 prepubertal children with Type 1 diabetes and in 31 healthy children who were
      exposed to cow's milk or dairy products to see whether differences in antibody
      titers exist in this young age group. Antibodies binding to beta-casein were also
      evaluated by immunoblotting analysis. RESULTS: Elevated levels of beta-casein
      antibodies were found in bottle-fed infants compared to breast-fed infants
      (p<0.0001). Antibody levels to bovine beta-casein were also significantly higher
      in children with Type 1 diabetes compared to age-matched controls (p=0.03). By
      western blot analysis we confirmed specific binding to bovine beta-casein in
      bottle-fed infants, in children with Type 1 diabetes and in controls exposed to
      cow's milk, but not in infants who were exclusively breast-fed. CONCLUSIONS: The
      results of this study indicate that breastfeeding within the first 4 months of
      life prevents the generation of antibody response to bovine beta-casein despite
      the mothers' consumption of cow's milk during the breastfeeding period. These
      findings may have relevance for disease prevention.

PMID- 11241890
TI  - Cataract development in diabetic sand rats treated with alpha-lipoic acid and its
      gamma-linolenic acid conjugate.
AB  - BACKGROUND: Diabetes commonly leads to long-term complications such as cataract.
      This study investigated the effects of alpha-lipoic acid (LPA) and its gamma
      linolenic acid (GLA) conjugate on cataract development in diabetic sand rats.
      METHODS: Two separate experiments were conducted. In Experiment 1, sand rats were
      fed a "high-energy" diet (70% starch), an acute model of Type 2 diabetes, and
      injected with LPA. In Experiment 2, the animals received a "medium-energy" diet
      (59% starch), a chronic diabetic model, and were intubated with LPA or its GLA
      conjugate. Throughout the experiments, blood glucose levels and cataract
      development were measured. At the termination of the experiments, lens aldose
      reductase (AR) activity and lenticular reduced glutathione (GSH) levels were
      analyzed. RESULTS: LPA injection significantly inhibited cataract development and
      reduced blood glucose levels in rats fed the "high-energy" diet. Lens AR activity
      tended to be lower, while lenticular GSH levels increased. In sand rats fed a
      "medium-energy" diet (59% starch), LPA intubation had no effect on blood glucose
      levels and cataract development but GSH levels were increased. In contrast, sand
      rats intubated with GLA conjugate showed the highest blood glucose levels and
      accelerated cataract development. The conjugate treatment also decreased
      lenticular GSH content. CONCLUSIONS: The hypoglycemic effects of LPA are
      beneficial in the prevention of acute symptoms of Type 2 diabetes. It remains to
      be shown that the antioxidant activity of LPA is responsible for prevention or
      inhibition of cataract progression in sand rats.

PMID- 11241893
TI  - Achieving optimal diabetic control in adolescence: the continuing enigma.
AB  - The transition from childhood through adolescence to adulthood is a difficult
      stage, particularly for patients with type 1 diabetes. The yearning for autonomy
      and independence, as well as the hormonal changes around the time of puberty, can
      manifest in poor glycaemic control. The focus on diet and weight increases the
      prevalence of eating disorders, compounding the difficulties in supervising
      diabetes patients. This can be exacerbated by the realisation that hyperglycaemia
      induces weight loss and the use of this knowledge to further manipulate diabetes
      control to gain a desired body image. The management of adolescents with type 1
      diabetes is therefore challenging and requires close collaboration between
      psychological medicine and diabetes teams. This review describes the difficulties
      frequently encountered, with a description of four cases illustrating these
      points. Case 1 demonstrates the problem of needle phobia in a newly diagnosed
      patient with type 1 diabetes leading to persistent hyperglycaemia, the
      recognition of weight loss associated with this and the development of bulimia.
      The patient's overall management was further complicated by risk-taking
      behaviour. By the age of 24 years, she has developed diabetic retinopathy and
      autonomic neuropathy and continues to partake in risk-taking behaviour. Case 2
      illustrates how the lack of parental support shortly after the development of
      type 1 diabetes led to poor glycaemic control and how teenagers often omit
      insulin to accommodate lifestyle and risk-taking behaviour. Case 3 further
      exemplifies the difficulty in managing patients with needle phobia and the fear
      of hypoglycaemia. Case 4 adds further weight to the need for parental support and
      the impact of deleterious life events on glycaemic control by manipulation of
      insulin dosage.

PMID- 11241892
TI  - Treatment of diabetes with vanadium salts: general overview and amelioration of
      nutritionally induced diabetes in the Psammomys obesus gerbil.
AB  - BACKGROUND: Numerous investigations have demonstrated the beneficial effect of
      vanadium salts on diabetes in streptozotocin (STZ)-diabetic rats, in rodents with
      genetically determined diabetes and in human subjects. The amelioration of
      diabetes included the abolition of hyperglycemia, preservation of insulin
      secretion, reduction in hepatic glucose production, enhanced glycolysis and
      lipogenesis and improved muscle glucose uptake through GLUT4 elevation and
      translocation. The molecular basis of vanadium salt action is not yet fully
      elucidated. Although evidence has been provided that the insulin receptor is
      activated, the possibility exists that cytosolic non-receptor tyrosine kinase,
      direct phosphorylation of IRS-1 and activation of PI3-K, leading to GLUT4
      translocation, are involved. The raised phosphorylation of proteins in the
      insulin signaling pathway appears to be related to the inhibition of protein
      tyrosine phosphatase (PTPase) activity by vanadium salts. NOVEL EXPERIMENTS: The
      model utilized in our study was Psammomys obesus (sand rat), a desert gerbil
      which becomes hyperglycemic and hyperinsulinemic on an ad libitum high energy
      (HE) diet. In contrast to the previously investigated insulin deficient models,
      vanadyl sulphate was used to correct insulin resistance and hyperinsulinemia,
      which led to beta-cell loss. Administration of 5 mg/kg vanadyl sulfate for 5 days
      resulted in prolonged restoration of normoglycemia and normoinsulinemia in most
      animals, return of glucose tolerance to normal, and a reduction of hepatic
      phosphoenolpyruvate carboxykinase activity. There was no change in food
      consumption and in regular growth during or after the vanadyl treatment.
      Pretreatment with vanadyl sulfate, followed by transfer to a HE diet,
      significantly delayed the onset of hyperglycemia. Hyperinsulinemic-euglycemic
      clamp of vanadyl sulfate treated Psammomys demonstrated an improvement in glucose
      utilization. However, vanadyl sulfate was ineffective when administered to
      animals which lost their insulin secretion capacity on protracted HE diet, but
      substantially reduced the hyperglycemia when given together with exogenous
      insulin. The in vitro insulin activation of liver and muscle insulin receptors
      isolated from vanadyl treated Psammomys was ineffective. The in vivo vanadyl
      treatment restored muscle GLUT4 total protein and mRNA contents in addition to
      membrane GLUT4 protein, in accordance with the increased glucose utilization
      during the clamp study. These results indicate that short-term vanadyl sulfate
      treatment corrects the nutritionally induced, insulin resistant diabetes. This
      action requires the presence of insulin for its beneficial effect. Thus, vanadyl
      action in P. obesus appears to be the result of insulin potentiation rather than
      mimicking, with activation of the signaling pathway proteins leading to GLUT4
      translocation, probably distal to the insulin receptor.

PMID- 11241894
TI  - The 36th Annual Meeting of the European Association for the Study of Diabetes
      (EASD), Jerusalem, Israel, 17-21 September 2000.

PMID- 11241896
TI  - DNA flow cytometry and bladder irrigation cytology in detection of bladder
      carcinoma.
AB  - In this study we assessed the role of DNA flow cytometry (FCM) as an adjunct to
      bladder irrigation cytology to detect carcinoma of the bladder. We selected only
      those cases who had urinary symptoms and cystoscopic examination or histology
      proven cases of bladder cancer who underwent cystoscopy for a follow-up study.
      Cystoscopy, cytologic examination, and DNA FCM were performed in every case.
      There were 9 fresh cases and 21 follow-up cases of proven transitional-cell
      carcinoma (TCC) of the bladder. Cystoscopy revealed growth in all 9 fresh cases
      as well as in 11 follow-up cases. Cytology was positive in 16 cases, out of which
      there were 8 each of fresh and recurrent cases. None of the cases showed positive
      cytology with negative cystoscopy findings. DNA FCM was positive in 13 cases.
      Aneuploidy was detected in 5 cases, out of which there were 3 hyperdiploid and 2
      hypodiploid cases. Nine cases had high (equal or more than 10%) S and G2-M phase
      cells, ranging from 10-19.36%. One case showed aneuploidy along with high S-G2M
      phase. Both cytology and DNA FCM were positive in 9 cases. In 2 cases, DNA FCM
      showed aneuploidy, but cytology and cystoscopy were negative. The sensitivity and
      specificity of the bladder wash cytology were 80% and 100%, and those for DNA FCM
      were 55% and 83.3%, respectively. We conclude that both bladder wash cytology and
      DNA FCM techniques should be done in all the cases of suspected TCC to detect
      more number of positive cases.

PMID- 11241897
TI  - Relation between DNA ploidy status and the expression of the DNA-mismatch repair
      genes MLH1 and MSH2 in cytological specimens of melanoma lymph node and liver
      metastases.
AB  - DNA-mismatch repair is essential for preventing genetic instability, and its
      important protective role has been demonstrated in several tumors. The main aim
      of this study was to investigate the expression of MLH1 and MSH2 (on the RNA
      level) in melanoma liver and lymph node metastases, and to define the relation
      between DNA ploidy status and mismatch repair gene expression. MLH1 was found in
      29/33 melanoma lymph node and in 5/17 melanoma liver metastases. MSH2 was present
      in 26/33 lymph node and 5/17 liver metastases. A comparison of MLH1 and MSH2
      positive and negative melanoma metastases showed that there were highly
      significant differences in the percentages of diploid cells, aneuploid cells
      between 4c and 8c, octaploid cells, and 5c exceeding rate. This fact confirms the
      strong relation between the loss of DNA-mismatch repair gene expression and
      advanced DNA aneuploidy status in melanoma metastases.

PMID- 11241898
TI  - Fine-needle sampling of primary neuroendocrine carcinomas of salivary glands:
      cytohistological correlations and clinical analysis.
AB  - Fine-needle samplings of nine examples of primary neuroendocrine carcinoma of
      salivary glands were evaluated for their cytologic characteristics and were
      correlated with the corresponding histological sections. Consistent cytological
      findings were dispersed or loose clusters of poorly differentiated small- to
      intermediate-sized cells and occasional smudged nuclei. Mild to moderate nuclear
      pleomorphism, scant or absent cytoplasm, and nuclear molding were also observed.
      Rosette-like patterns and multinucleated cells were occasionally seen.
      Immunostaining of one recent case showed positivity for chromogranin and keratin.
      The differential diagnosis of primary and metastatic tumors with neuroendocrine
      features of the salivary glands is discussed.

PMID- 11241899
TI  - Papillary carcinoma of the thyroid and its variants: a cytohistological
      correlation.
AB  - Fine-needle aspiration cytology (FNAC) is considered highly specific for the
      diagnosis of papillary carcinoma of the thyroid (PCT). In recent years, several
      variants of PCT have been described. An attempt was made to gauge the accuracy of
      classification of variants of PCT on aspirates. Cytology smears from 124 of 150
      cases of histologically proven PCT with a prior FNAC were reviewed over a 16-yr
      period. A diagnosis of papillary carcinoma on FNAC was made in 93 cases. Further
      subclassification of these cases was done on cytology and tissue sections
      independently. The variants of PCT classified on FNAC were classical PCT (PCT
      CL), 76 cases; Hurthle-cell variant (PCT-HCV), 3 cases; follicular variant (PCT
      FV), 6 cases; tall-cell variant (PCT-TCV), 2 cases; high-grade variant (PCT-HG),
      2 cases; and 2 cases each which were debatably PCT-CL/PCT-FV and PCT-CL/PCT-HG.
      Cytology typing was accurate in 65 of the 72 classical variants, while only 7 of
      the 22 follicular variants were correctly identified on cytology. Two of the 3
      high-grade papillary carcinomas (PCT-HG) were identified on FNAC, and the
      solitary case of tall-cell variant could readily be classified on cytology. In
      conclusion, identification of the various variants of PCT is possible, though
      difficulty is encountered in correctly categorizing the follicular variant, which
      is often mistaken for a follicular neoplasm. Also, identification of the solid
      variant and the papillary carcinoma with nodular fasciitis-like stroma was a
      problem on cytology. Another interesting observation in our series is that an
      admixture of various cell types was seen in the smears and corroborated on
      histology to be present in focal areas.

PMID- 11241901
TI  - Abdominal fat pad aspiration biopsy for tissue confirmation of systemic
      amyloidosis: specificity, positive predictive value, and diagnostic pitfalls.
AB  - Abdominal fat pad fine-needle aspiration biopsy (FNAB) is considered the method
      of choice for confirmation of systemic amyloidosis. Due to our impression that
      positive results are rare in our FNA service, we retrospectively analyzed our
      results. Forty-five samples collected from 45 patients over 3 yr were reviewed.
      Of the 7 patients with positive Congo red-stained FNAB specimens, all 7 (100%)
      had documented amyloidosis. Of the 33 patients with negative Congo red fat
      samples, 28 (85%) were disease-free. Of the 5 patients with inadequate samples, 2
      (40%) were later diagnosed with disease. We demonstrate excellent specificity
      (100%). The positive predictive value, documented in only a few previous studies,
      is likewise excellent (100%). Sensitivity is low (58%) and inadequacy is high
      (11%). Improvement in technique, such as concurrent cell block preparation, may
      help avoid inadequate specimens. Difficulties in confirming amyloidosis also
      include interpretation of the Congo red stain (pale-stained amyloid fibrils and
      collagen birefringence).

PMID- 11241900
TI  - Detection of malignant effusions: comparison of a telomerase assay and cytologic
      examination.
AB  - Telomerase is inactive in most somatic cells, but has been found to be
      reactivated in a majority of cancers. Our principal goal was to test whether the
      presence of telomerase activity concurred with positive cytology, and was thus of
      potential use in detecting cancer cells in effusions. The telomeric repeat
      amplification protocol (TRAP) assay and cytological examination were performed in
      a blinded fashion on 91 unselected effusions, for which laboratory processing was
      done according to standard procedures. In our series, 30% (27/91) of samples were
      found to be malignant by cytology. Of these, 19 (70%) were also positive in the
      TRAP assay. Of the 8 telomerase-negative cytology-positive samples, RNA integrity
      was generally poor, indicating suboptimal sample conservation for molecular
      analysis. Negative cytology in the presence of telomerase activity was observed
      in 17 effusions. Of these, 11 were from patients with advanced cancer, and thus a
      diagnosis of malignant effusion should be suspected. The TRAP assay for
      telomerase activity holds promise in the analysis of effusions, but its routine
      use as an adjunct to cytology awaits further confirmation of its positive
      predictive value.

PMID- 11241902
TI  - Fine-needle aspiration diagnosis of unusual cutaneous neoplasms of the scalp in
      HIV-infected patients: a report of two cases and review of the literature.
AB  - We report on two unusual, non-AIDS-defining scalp neoplasms, Merkel-cell
      carcinoma (MCC) and malignant melanoma, in 2 men with acquired immunodeficiency
      syndrome (AIDS). In the first patient, metastatic MCC was initially diagnosed by
      fine-needle aspiration (FNA) of a posterior cervical lymph node, based on the
      cytomorphology and the characteristic immunohistochemical and ultrastructural
      features. No skin lesion was initially apparent, but a 0.3-mm scalp primary was
      found during the ensuing neck dissection. In the second patient, recurrent and
      metastatic malignant melanoma from a Breslow 1.3-mm scalp primary was diagnosed
      by FNA. Both patients developed generalized disease in a relatively short time,
      despite their small primaries. These cases illustrate the occurrence of Merkel
      cell carcinoma and melanoma in AIDS patients, and stress the need to consider
      these unusual cutaneous neoplasms when evaluating lymph node FNA samples from HIV
      positive patients, especially since both may present as metastases from
      clinically occult primaries.

PMID- 11241903
TI  - Fine-needle aspiration of chromophobe renal-cell carcinoma metastatic to the
      thyroid gland.
AB  - Chromophobe renal cell carcinoma is an unusual variant of renal carcinoma that
      has less aggressive behavior than clear cell carcinomas. There are few documented
      cases of metastases, none of which occurred in the thyroid gland. A case is
      presented of chromophobe renal cell carcinoma metastatic to the thyroid eight
      years after right nephrectomy, suspected by FNA-biopsy and confirmed
      histologically. Although metastases of chromophobe renal cell carcinoma are rare,
      they may also present in thyroid, even many years after primary tumor diagnosis,
      just like clear cell carcinomas. Even though the FNA cytology of chromophobe
      renal cell carcinoma has distinctive features, in the context of the thyroid, it
      can be mistaken for a primary tumor of that organ. In our case, the history of a
      previous renal tumor was essential in suggesting a metastatic lesion, and
      histologic and ultrastructural features allowed its precise identification.

PMID- 11241904
TI  - Clinical impact of identifying Trichomonas vaginalis on cervicovaginal
      (Papanicolaou) smears.
AB  - The purpose of this study was to understand how clinicians manage asymptomatic
      women after Trichomonas has been reported on Papanicolaou (Pap) smears. Clinical
      information was obtained from questionnaires sent to healthcare providers
      whenever Trichomonas was identified during the study period. Trichomonas was
      identified in 173 (1.4%) of 12,547 Pap smears examined. Completed questionnaires
      were returned on 95 (55%) patients, and 92 patients were included in this study.
      Sixty-three (68%) patients were asymptomatic, 16 (18%) had symptoms
      characteristic of infection, and 13 (14%) had nonspecific symptoms. Twenty-six
      (28%) patients received treatment during the original clinic visits. After the
      Pap smear reported Trichomonas, 49 (81%) of the 66 patients were contacted and
      treated, 7 (12%) were contacted and scheduled for further evaluation, and no
      action was taken on the remaining 10 (17%) patients. There was a significant
      association between presenting with symptoms and receiving treatment at the time
      of the original visit (P < 0.001), but not with receiving subsequent treatment.
      Clinical suspicion of infection was also associated with receiving treatment at
      the time of the original visit only (P < 0.001). Clinical suspicion of infection
      correlated with symptoms and results of wet mount smears (P < 0.001). In
      conclusion, the Pap smear report of Trichomonas identification directly impacted
      the management of 61% of patients and served as confirmation for clinical
      management in another 28% who had received treatment at the time of original
      visit. Despite the fact that most patients were asymptomatic, the majority
      received treatment and/or evaluation after the Pap smear report was received.

PMID- 11241905
TI  - Application of laser scanning cytometry for evaluation of DNA ploidy in routine
      cytologic specimens.
AB  - The laser scanning cytometer (LSC) is a relatively new instrument that combines
      the features of both flow and static image cytometry. The purpose of this study
      was to examine the application of the LSC for evaluation of DNA ploidy in routine
      cytologic specimens. The material for this study consisted of 60 routine
      cytologic specimens obtained from 33 males and 27 females ranging in age from 23
      87 yr (mean, 58 yr). The specimens were simultaneously stained with propidium
      iodide and FITC-cytokeratin, either on Thin-Prep slide (35 cases) or in a
      concentrated cell suspension (25 cases). In each case a minimum of 500 cells was
      evaluated (range, 527-17,963; mean, 3,889). All abnormal cell populations were
      relocated for the presence of malignant cells. The results were defined as
      diploid and aneuploid/tetraploid. In 10 bladder washes, the results of LSC were
      compared to results of flow cytometry. Out of 60 specimens, 7 (11%: 6 bladder
      washes and 1 renal wash) were excluded due to low cellularity. Of the remaining
      53 cases, 11 (20%) were aneuploid/tetraploid, and 42 (80%) were diploid. All but
      one cytologically diagnosed malignancy had abnormal DNA content. Additionally,
      two bladder washes diagnosed as suspicious and atypical were aneuploid. All
      abnormal LSC results were confirmed by relocation of the cells. The concordance
      between flow cytometry and LSC in the 10 control bladder washes was 100%. In
      conclusion, LSC proved to be a suitable instrument for the evaluation of DNA
      ploidy in routine cytologic specimens.

PMID- 11241906
TI  - Cytological aspects of melanotic variant of medullary thyroid carcinoma.
AB  - We had the opportunity to examine a case of fine-needle aspiration (FNA) of a
      melanotic variant of medullary thyroid carcinoma (MTC) in a 20-yr-old man. The
      patient presented a single node, hardened and mobile upon deglutition, in the
      right lobe of the thyroid, for 9 mo, without symptoms of glandular dysfunction.
      Calcitonin (138 pg/ml), urinary calcium (177 mg/dl), and the carcinoembryonic
      antigen (341 ng/ml) were increased. The nodular aspirate, drawn by FNA, was
      represented by pleomorphic cells, with frequent intranuclear cytoplasmic
      inclusions, sometimes bi- or multinucleated, with abundant, finely granular
      cytoplasm, sometimes containing a brown pigment resembling melanin. An
      immunohistochemical study using monoclonal antibodies (Dako Corp., Carpinteria,
      CA) showed that the neoplastic cells were intensely and diffusely positive for
      calcitonin and chromogranin, and focally positive for HMB45. In view of these
      findings, the case was characterized as a melanotic variant of medullary
      carcinoma, a rare type of neoplasia, but having a prognosis similar to the
      classical variant of MTC.

PMID- 11241907
TI  - Soft-tissue osteosarcoma with prominent aneurysmatic bone cyst-like features: a
      case report.
AB  - We describe the cytological features of a soft-tissue high-grade spindle and
      pleomorphic sarcoma. The smears showed hypercellularity composed of pleomorphic
      round and elongated cells, and a striking population of multinucleated osteoclast
      type giant cells. Microscopically the tumor showed multiple patterns such as
      highly cellular pleomorphic, less cellular, and hyalinized areas with neoplastic
      cartilage and osteoid, and areas with hemorrhage and multicystic appearance with
      numerous osteoclastic giant cells, resembling aneurysmal bone cysts.
      Immunohistochemical studies showed positivity for vimentin, while chondroid
      tissue was positive for S-100, and osteoclastic giant cells stained positively
      for CD68. Due to the varied microscopic patterns, the differential diagnosis
      included many tumors containing osteoclastic giant cells and osteochondroid
      tissue.

PMID- 11241908
TI  - Atypical hemangioma of the breast: a diagnostic pitfall in breast fine-needle
      aspiration.
AB  - We report on the fine-needle aspiration (FNA) cytology of atypical hemangioma of
      the breast in a 52-yr-old female. The patient presented with a 2-cm palpable left
      breast mass. An FNA of the mass was performed following a mammogram,
      corresponding to the palpable breast mass. The FNA demonstrated the presence of
      numerous atypical single spindle cells scattered throughout a hemorrhagic
      background. An unequivocal diagnosis of malignancy was not rendered in this case.
      However, the degree of cytologic atypia suggested a malignant process, and a
      recommendation for an excisional biopsy was made. Atypical hemangioma should
      therefore be included in the differential diagnosis of angiosarcoma and other
      benign and malignant spindle-cell lesions of the breast encountered on cytologic
      samples.

PMID- 11241909
TI  - Rapid rescreen: a viable alternative to 1:10?
AB  - A rapid screen of those Pap smears designated as within normal limits is a
      quality control requirement of all UK laboratories. However in the United States
      standard QC involves a combination of 1:10 and selective rescreening procedures.
      Forty participants at the joint ASCT/ACP meeting in Las Vegas rapid screened 50
      slides as part of a rapid screening workshop. They used different patterns of
      screening but were allowed only 60 seconds for each slide. Thirty of the slides
      contained abnormal cells but all had originally been called negative or
      unsatisfactory and as such were "false negatives". Ability to identify the
      abnormal smears varied considerably between individuals but overall rapid
      screening correctly identified 54% of the ascus or LGSIL cases and 61% of the
      HGSIL cases. The results demonstrate the superiority of such a rapid screen over
      1:10 and question what if any role this outdated practice should have.

PMID- 11241910
TI  - Cytopathology of adrenal cortical oncocytoma.

PMID- 11241911
TI  - Fine-needle aspiration biopsy of epithelial-myoepithelial carcinoma.

PMID- 11241912
TI  - Detection of fungal organisms in pulmonary cytology samples of chronic
      granulomatous disease: a comparison of alternate techniques.

PMID- 11241914
TI  - Current status of total mesorectal excision and autonomic nerve preservation in
      rectal cancer.
AB  - Two decades have passed since the late 1970s, which witnessed the introduction of
      total mesorectal excision (TME)-based operations for rectal cancers on both sides
      of the Atlantic. Since the introduction of TME, clinical experience has been
      reported widely in the form of single- and multisurgeon reports from wide
      geographic regions with multiple participants, and from specialty services with
      narrow focus and high levels of expertise. All of these published results
      conclude that in comparison with conventionally practiced blunt surgery for
      rectal cancer, TME-based (i.e., anatomically correct, sharply performed)
      operations are associated with significantly lower rates of pelvic (local)
      recurrences, a significantly higher rate of survival, and significantly lower
      long-term morbidity. The latter is accomplished through dramatically higher rates
      of sphincter preservation, and the preservation of both sexual and urinary
      functions. Overall, there is a remarkable similarity in the clinical results that
      have been reported from diverse centers. TME now forms the basis of large
      randomized clinical trials in which the role of adjuvant therapy is being
      reexamined. The current status of TME is reviewed, and the authors' clinical
      results of a consecutive series of 544 TME-based operations performed through
      1998 are updated.

PMID- 11241915
TI  - Role of the surgeon as a variable in the treatment of rectal cancer.
AB  - Increasingly, data are being accumulated on the influence of intersurgeon
      variability on outcome after curative surgical treatment of rectal carcinoma.
      Thus, today the individual surgeon has to be considered as an independent factor
      influencing locoregional recurrence, as well as survival rates. In general,
      higher local control and survival can be expected for specialized colorectal
      surgeons. There are no clear correlations between surgical volume and outcome.
      Interinstitutional variability in treatment results reflects intersurgeon
      variability, but analysis is generally more difficult because of a lack of
      homogeneity with respect to different confounding factors. There are several
      factors in surgical technique that are important for long-term outcome. Of
      greatest apparent importance is the adequacy of mesorectal excision (for
      carcinomas of the middle and lower third, total mesorectal excision; for
      carcinomas of the upper third, mesorectal excision down to a mesorectal plane 5
      cm distal to the gross tumor margin detected by the surgeon in situ).
      Furthermore, intraoperative local tumor spillage (tumor perforation during
      mobilization, incision into the tumor), en bloc resection technique, skill, and
      the extent of regional lymphadenectomy may influence outcome. For quality
      assurance, detailed operative reports are required, as well as histopathology
      examinations concerning indicators of surgical oncologic quality discernable from
      the resection specimens. In future clinical trials of multimodal treatment of
      rectal cancer, quality assurance of surgery and pathology is necessary for
      consideration of the surgeon and surgical technique prognostic factors.

PMID- 11241916
TI  - Adjuvant therapy for resectable rectal adenocarcinoma.
AB  - The mainstay of treatment for rectal cancer over the past 100 years has been
      surgical resection. However, for the majority of rectal cancers treated
      conventionally by resection alone, locoregional recurrence is the major mode of
      failure. Over the past several decades, significant progress has been made in
      developing effective adjuvant regimens. In the United States, postoperative
      chemoradiation is standard treatment for T3 or node-positive patients. However,
      preoperative radiation with or without chemotherapy decreases local recurrence,
      increases sphincter preservation, and may improve survival. The purpose of this
      article is to review the role of adjuvant therapy in resectable rectal cancers
      and to update the status of ongoing randomized trials.

PMID- 11241917
TI  - European trials with total mesorectal excision.
AB  - The outcome after surgery for rectal cancer differs markedly between patient
      series regarding local recurrence rates and survival. A high incidence of local
      recurrence is associated with conventional, nonstandardized procedures. To
      improve results of surgery, various additional treatments, such as radiotherapy,
      chemotherapy, and immunotherapy, have been tested. The Swedish Rectal Cancer
      Trial (SRCT) was the first trial to show that better local control achieved with
      preoperative radiotherapy resulted in improved survival. In recent years local
      control and survival have been further improved by the introduction of
      standardized total mesorectal excision (TME) surgery. A major problem of
      published studies on adjuvant therapy is that surgery was not standardized in
      these studies. Furthermore, quality control of the surgical technique by
      standardized pathological examination of the specimen is absent in most studies.
      In Europe, TME has become the preferred standard of operative management for
      rectal cancer. Adjuvant therapy studies should now be reexamined based on a
      platform of standardized, optimal surgery and pathology. We studied the European
      trials in which TME surgery is intentionally performed. Most of these trials are
      still in progress, with follow-up too short for definitive results, apart from
      interim analyses. However, the Dutch TME trial has already shown that performing
      a large, multicenter trial with quality control of both surgery and pathology is
      feasible.

PMID- 11241918
TI  - Role of endorectal ultrasound in the conservative management of rectal cancers.
AB  - Endorectal ultrasonography (ERUS) extends the ability of the clinician to define
      the clinical features assessed on routine physical examination, and remains the
      best modality for accurately staging depth of penetration and presumptive nodal
      status in rectal cancers. The success of conservative management of rectal
      cancers is predicated on proper patient selection. The preoperative selection of
      the ideal patient for local therapies can be difficult, and the decision-making
      process takes into account many critical factors. Careful assessment of the T and
      N stages is critical in determining the success of conservative therapies, and
      directing treatment algorithms. Local resections with curative intent are limited
      to patients with T1N0 rectal cancers, and select patients with T2N0 tumors with
      favorable pathological criteria. Conservative management may also be extended to
      patients identified with significant underlying comorbid conditions staged
      preoperatively with unfavorable T2/T3 lesions, often combined with adjuvant
      therapies in a palliative setting. In addition, ERUS may have a role in the
      selection of those patients with more advanced lesions to neoadjuvant
      chemoradiation, followed by radical resection. Though not clearly defined, ERUS
      is evolving in its role in the postoperative follow-up of patients treated
      conservatively for rectal cancers, and can lead to the early detection of local
      recurrences. The widespread use of ERUS remains limited due to high operator
      variability and errors in interpretation; however, the role of ERUS in the
      postoperative management of rectal cancers is evolving and requires further
      evaluation.

PMID- 11241919
TI  - Role of local excision in the treatment of rectal cancer.
AB  - Local excision (LE) of properly selected rectal cancers can provide long-term
      survival, with minimal morbidity, negligible mortality, and excellent functional
      results. The role of LE has evolved over the past century. Initially, to avoid
      the excessive mortality of abdominal surgery, aggressive LE was performed to
      control the symptoms of rectal cancer. As abdominal surgery became safer, LE was
      restricted for use in palliation or high-risk patients. Better preoperative tumor
      staging resulted in an expanded role for LE, including curative-intent treatment
      of selected T(1-2) rectal cancers. Techniques for LE include snare polypectomy,
      transanal excision, transanal endoscopic microsurgery, and posterior approaches.
      The high local recurrence rate and compromised survival reported in modern
      series, despite efforts to properly select patients with cancers suitable for LE,
      have convinced the authors to restrict the use of curative-intent LE in good-risk
      patients only to the most favorable rectal cancers. Close follow-up after LE is
      critical, because radical surgical salvage is usually possible if recurrence is
      identified promptly. Whether adjuvant chemoradiation can expand the role of
      curative intent LE remains controversial.

PMID- 11241920
TI  - Preservation of rectal function after low anterior resection with formation of a
      neorectum.
AB  - Recent advances in surgery have enabled low rectal cancers to be resected, while
      at the same time restoring bowel continuity and preserving the anal sphincter.
      Although a permanent stoma is avoided and the operation is oncologically sound,
      function may be compromised. Many patients with a straight coloanal anstomosis
      suffer from urgency, incontinence, and bowel frequency-the so-called anterior
      resection syndrome. Over the last 15 years, surgical developments have aimed at
      improving function after restoration of bowel continuity, essentially by creating
      a neorectum. The best known and most widely practiced operation involves
      formation of a colonic J-pouch. The physiological and functional outcomes of the
      colonic J-pouch are discussed, along with controversies surrounding construction.
      Although a J-pouch improves some aspects of function, the results are not
      perfect. Alternatives to the colonic J-pouch are appraised, indicating future
      areas of development.

PMID- 11241921
TI  - Lateral ligament: its anatomy and clinical importance.
AB  - Since Miles proposed abdominoperineal excision as a radical surgery for rectal
      cancer in 1908, surgeons have recognized the lateral ligament in the pararectal
      space of their patients and attached clinical importance to it, although
      anatomists did not describe any such configuration in cadavers. By analyzing an
      experience of 421 lower rectal cancer cases at the Cancer Institute Hospital in
      Tokyo, discussion of the lateral ligament was focused on its relationship to the
      fascial arrangements in the pelvis, the pelvic autonomic nervous system, and the
      lymphatic drainage of the rectum. The lateral ligament is not an anatomical term,
      but a clinical or surgical one. It exists in a living pelvis as a condensation of
      connective tissue around the middle rectal artery and is divided into two
      segments by the inferior hypogastric nerve plexus inside it and the visceral
      endopelvic fascia around it. The lateral ligament is a pathway of blood vessels
      and nerve fibers toward the rectum and lymphatic vessels from the lower rectum
      toward the iliac lymph nodes. Therefore, the lateral ligament plays a critical
      role in surgery for lower rectal cancer in two respects: the anatomic extent of
      resection for curing rectal cancer, and the preservation of sexual function.

PMID- 11241922
TI  - Laparoscopic total mesorectal excision with autonomic nerve preservation.
AB  - Laparoscopy has greatly influenced abdominal surgery. We hypothesize that the
      benefits of minimally invasive surgery are applicable to rectal cancer. A cadaver
      model of laparoscopic rectal resection with total mesorectal excision (TME) and
      autonomic nerve preservation was utilized to explore this hypothesis. The
      principles of TME were followed, including high vascular ligation, sharp
      mesorectal dissection, and identification and preservation of the autonomic
      pelvic nerves. After proving feasibility in the cadaver model, a clinical study
      was performed on patients with mid to low rectal cancers. We observed acceptable
      morbidity with this minimally invasive technique of rectal resection and TME. We
      conclude that there is growing evidence that laparoscopic methods can be applied
      to patients with rectal cancer.

PMID- 11241924
TI  - [Asbestos and disease: review of the scientific knowledge and a rationale for
      urgent change in the current Brazilian policy about this question].
AB  - This paper is a state-of-the-art review of scientific knowledge on both the
      health effects of asbestos fiber inhalation and possibilities for safe and
      sustainable prevention, from an ethical, political, and technological point of
      view. The author provides scientific background and arguments from the ongoing
      discussion in Brazil concerning the need to redefine current asbestos policy, in
      order to establish a more advanced and appropriate policy whose priority is the
      protection of life, human health, and the environment. The first part deals with
      several technological and economic aspects of asbestos-chrysotile. In the second
      part, the author presents and discusses a bibliographic review of the
      construction of scientific knowledge on the health effects of asbestos fibers,
      first within an international perspective, and then (in the third part), from a
      Brazilian view. The fourth part analyzes the current debate on the fibrogenicity
      and carcinogenicity of asbestos-chrysotile. Some current responses from the
      international community towards the asbestos-chrysotile ban are also discussed.
      Finally, the author discusses the historical inadequacy of Brazilian asbestos
      policy and the urgent need to revise it to include a ban on asbestos-chrysotile
      in this country.

PMID- 11241925
TI  - Social ecosystem health: confronting the complexity and emergence of infectious
      diseases.
AB  - The emergence and re-emergence of infectious diseases and their rapid
      dissemination worldwide are challenging national health systems, particularly in
      developing countries affected by extreme poverty and environmental degradation.
      The expectations that new vaccines and drugs and global surveillance would help
      reverse these trends have been frustrated thus far by the complexity of the
      epidemiological transition, despite promising prospects for the near future in
      biomolecular research and genetic engineering. This impasse raises crucial issues
      concerning conceptual frameworks supporting priority-setting, risk anticipation,
      and the transfer of science and technology's results to society. This article
      discusses these issues and the limitations of social and economic sciences on the
      one hand and ecology on the other as the main theoretical references of the
      health sciences in confronting the complexity of these issues on their own. The
      tension between these historically dissociated paradigms is discussed and a
      transdisciplinary approach is proposed, that of social ecosystem health,
      incorporating these distinct perspectives into a comprehensive framework.

PMID- 11241926
TI  - [Health policy polarization in Mexico].
AB  - In the last 17 years, health policy in Mexico has been shifted from a conception
      of integrated health care and a gradually extended coverage as a major
      responsibility of the State and health care public institutions, to in the one
      hand, a very active promotion of market and private profit in health services and
      in the other, poverty relief programs. In this paper we identify different
      periods corresponding to the last three presidential terms. Each clearly
      represent different stages of health sector reform: transitional (1982-1988),
      mercantilisation and poverty relief (1988-1994) and, strengthening of the so
      called health markets (1994-2000). The analyzed transformation is part of the set
      of secondary reforms subordinated to the structural adjustment and the economic
      and social megaprojects imposed by the international financial institutions.

PMID- 11241927
TI  - [Prevention of sexually transmitted diseases in women: association with
      socioeconomic and demographic variables].
AB  - Sexually transmitted diseases (STDs) have been a subject of discussion both among
      scientists and in the mass media, especially because of their association with
      the human immunodeficiency virus (HIV). We studied the adoption of specific
      protective behaviors for the prevention of STDs among women, as well as the
      associations between these behaviors and socioeconomic and demographic variables.
      This was a descriptive study based on secondary data from a previous study
      carried out in Campinas, Sao Paulo State, Brazil. A total of 635 women were
      selected using the social network ("snowball") technique. Subjects were
      classified into four groups: adolescents and adults of upper middle and lower
      socioeconomic status, respectively. Condoms were the STD prevention method most
      frequently mentioned by interviewees. A negative association was observed between
      having a steady partner and condom use in all the groups. The main reason
      mentioned for not using condoms was "having a single partner and trusting him".
      Among adolescents, a positive association was observed between schooling above
      the 8th grade and condom use, and a negative association was observed between age
      and condom use. Among adults, only condom use in general was also positively
      associated with socioeconomic status.

PMID- 11241928
TI  - [Prevalence of sleep disorders in the elderly].
AB  - This study was performed with senior citizens in Greater Metropolitan
      Guadalajara, Mexico, who live in private homes, alone, or with family. Of these,
      58% of men and 76% of women showed at least one symptom of sleep disorder
      according to the Goldberg General Health Questionnaire, while 8.5% were positive
      for all survey items. According to DSM IV criteria, 33.3% could be considered
      "cases" of sleep disorder, and none were under any type of treatment at the time
      of the study. These possible cases were apparently associated with gender and
      educational level, but not with marital status or age. In addition, no strong
      association was detected with the presence of depression, established according
      to Brink's Geriatric Depression Scale. Given the large amount of "possible cases"
      found that had not been previously detected and were not in any type of ad hoc
      treatment, we recommend promoting updated educational courses on this topic for
      health professionals (mainly doctors and nurses) in such a way as to facilitate
      timely case detection and thus increase and improve the accessibility of mental
      health services for the elderly population, increasing health education
      activities for this age group, their caregivers, and the general population.

PMID- 11241929
TI  - [Fulfilling of variables in the declarations of external cause of death of
      children and adolescents in Recife from 1979 to 1995].
AB  - This article analyzes the completion of death certificates related to external
      causes in children and adolescents residing in Recife, Pernambuco State, Brazil,
      from 1979 to 1995. The analysis focused on the extent to which the following
      variables were filled in: personal data (occupation, level of schooling, medical
      care, confirmation of diagnosis by post-mortem, and type of violence) and place
      (location and municipality of both occurrence and death). Using the chi-squared
      method, quantitative and/or qualitative flaws were found in most of the variables
      analyzed. In 1995, the "schooling" and "medical care" variables were recorded in
      only 5.7% and 17.9% of cases, respectively. Mismatches were observed between data
      on place of death and medical care, as well as between place of accident and
      number of accidents. The results suggest a dissociation between the objective of
      including the variable in the death certificate and its social function. The
      study provides the public sector with support for improved collecting and
      critical analysis of data in the mortality information system.

PMID- 11241930
TI  - [Physical growth in schoolchildren from Florianopolis, Santa Catarina State,
      Brazil: a case-control study].
AB  - This study was undertaken using a case-control, prevalence survey design, aimed
      at verifying the effects of socioeconomic, environmental, and
      biological/morbidity variables on the growth of schoolchildren from low-income
      families. The study focused on schoolchildren whose height/age (H/A) ratio was <
      or = 2SD (NCHS). Control groups were paired according to sex into two groups: C1,
      whose H/A ratio was between -1SD (NCHS) and the median, and C2, with the H/A
      ratio > median to +1 SD (NCHS). The Mantel-Haenszel test was used to verify each
      variable with regard to the H/A ratio, while non-conditional multivariate
      analysis was used to identify which of the variable blocks had a significant
      effect and, in the following stage, to identify the variables with a significant
      effect within each block. In the first stage, the variables with a significant
      effect for C1 were socioeconomic. For C2, socioeconomic, environmental, and
      morbidity/biological variables were significant. In the final model, the
      remaining significant variables for C1 were socioeconomic, while those for C2
      were socioeconomic and morbidity/biological. The authors conclude that
      socioeconomic variables are hierarchically superior to other risk factors.

PMID- 11241931
TI  - [Shared local health system management and community participation in Brazil].
AB  - The introduction of the Unified Health System (SUS) by the Brazilian government
      has helped enhance community participation. A survey in 12 municipalities in
      different States of the country focused on the decentralization process
      implemented by the Federal government (Basic Operational Ruling NOB01/93). Based
      on the ruling's implementation, community participation has improved in the
      municipalities, the number of local health councils has increased, and more local
      people have become involved in the process. Another important aspect of the new
      health policy has been the direct influence of the local health councils in
      managing the system. Local health councils have thus been an efficient channel
      for community involvement. This paper discusses how the population has been
      represented in such councils in the wake of the decentralization process. The
      authors ask, what is the relationship between social democracy and political
      democracy, and what kind of state reform should be carried out?

PMID- 11241932
TI  - [Reliability of the WPPSI-R test in the evaluation of cognitive development in
      preschool children].
AB  - The WPPSI-R scale (Wechsler Preschool and Primary Scale of Intelligence -
      Revised) is a psychometric test chosen as the evaluation tool in a study on
      preschool-age cognitive development in a cohort of very low birth weight (VLBW)
      premature children from the Fernandes Figueira Institute (IFF), applied by four
      previously trained psychologists. The objective of this study was to verify inter
      observer reliability in the test application. Two types of reliability study
      design were used: balanced incomplete blocks, to verify agreement in the
      application of the scale, and crossed design, to verify agreement in scoring of
      items. We studied 12 preschool children born at IFF (birthweight < 1,500g). The
      intraclass correlation coefficients (ICC) were: 0.82 (full-scale IQ), 0.89
      (verbal IQ), and 0.91 (performance IQ), in the incomplete block design study, and
      0.99, 0.98, and 0.99, respectively, in the crossed design study, indicating good
      reliability. Application of the WPPSI-R scale in the study of cognitive
      development of VLBW premature children at IFF proved adequate, as shown by these
      results.

PMID- 11241933
TI  - [Morbidity among job applicants in the Metropolitan Region of Salvador, Bahia,
      Brazil].
AB  - This cross-sectional study evaluates the pre-employment health status of job
      applicants, based on prevalence estimates of abnormal laboratory test results,
      clinical diagnosis, and a physician-signed fit-for-work assessment, which is
      mandatory in Brazil. The study population was a random sample of 1,237 male
      workers selected from medical records (1988-1996) from an Occupational Medical
      Center located in Salvador, the capital of Bahia State, Brazil. The data were
      from a single pre-employment medical assessment for each individual. The most
      common diseases were intestinal parasites (51.7%), anemia (12.8%), and
      hypertension (12.7%). Drivers showed a high prevalence of overweight (38.2%) and
      hypertension (16.2%). In addition to work-related risks and diseases,
      occupational hygiene and safety programs need to address prevailing illnesses and
      risk factors, which in this population are typical of poor living conditions.
      Special attention should to be given to drivers, who are at increased risk of
      cardiovascular disease.

PMID- 11241934
TI  - [Work-related accidents on oil drilling platforms in the Campos Basin, Rio de
      Janeiro, Brazil].
AB  - The offshore oil industry is characterized by complex systems in relation to
      technology and organization of work. Working conditions are hazardous, resulting
      in accidents and even occasional full-scale catastrophes. This article is the
      result of a study on work-related accidents in the offshore platforms in the
      Campos Basin, Rio de Janeiro State. The primary objective was to provide
      technical back-up for both workers' representative organizations and public
      authorities. As a methodology, we attempt to go beyond the immediate causes of
      accidents and emphasize underlying causes related to organizational and
      managerial aspects. The sources were used in such a way as to permit
      classification in relation to the type of incident, technological system,
      operation, and immediate and underlying causes. The results show the aggravation
      of safety conditions and the immediate need for public authorities and the
      offshore oil industry in Brazil to change the methods used to investigate
      accidents in order to identify the main causes in the organizational and
      managerial structure of companies.

PMID- 11241935
TI  - [Prenatal care at the primary health care level: an assessment of the structure
      and process].
AB  - With the aim of describing the structure and process by which prenatal care is
      provided at the primary health care level in the city of Pelotas in southern
      Brazil, a descriptive cross-sectional study was conducted. All 31 urban health
      care facilities were visited and their structure analyzed. A total of 839
      prenatal records from mothers who delivered in the six months prior to the
      beginning of the study were reviewed. The structure as a whole was classified as
      poor (only 70% of standard parameters were present), mainly due to deficiencies
      in the physical plant. Process assessment showed low coverage (53%) and an
      average of 5.3 visits. Only 37% of patient records showed adequate results
      (Kessner Index). Adding laboratory test results and routine procedures as
      complementary criteria, 31% and 5% of the records scored as adequate,
      respectively. In summary, overall quality of prenatal care provided at the
      primary health care level in Pelotas is poor. Mechanisms to increase staff
      adherence to both procedures and program logistics need to be developed.

PMID- 11241936
TI  - [Stillbirth as a perinatal health indicator].
AB  - The authors carried out a literature review of the subject "stillbirth", with
      special emphasis on its conceptual and epidemiological features, aimed at
      highlighting its importance as a perinatal health indicator.

PMID- 11241937
TI  - [RSI: object and pretext for constructing the work and health field].
AB  - This article presents a proposal for a research and action agenda in Workers'
      Health, taking the case of repetitive strain injury (RSI). It assumes that RSIs
      are both an object and a pretext for the Workers' Health area. As an object, RSIs
      demand both an understanding and resolution of problems as they present, and as a
      pretext, RSIs underscore the limits and contradictions of the paradigms adopted
      in Workers' Health. The article draws on data and questions raised in several
      studies.

PMID- 11241938
TI  - [Calibration of examiners for dental caries epidemiologic studies].
AB  - The aim of this study was describe a training and calibration exercise for dental
      caries and to discuss the use of validity and reliability statistical tests.
      Eight dentists examined seventeen 12 year-old schoolchildren using World Health
      Organization (1997) criteria. Data analysis included calculation of the DMF-T
      index, the percent agreement, and the kappa scores on a tooth-by-tooth basis.
      Inter-examiner agreement was tested against a gold standard examiner. Scores for
      measures of agreement calculated on a tooth-by-tooth basis were lower than those
      calculated for the whole mouth. The training and calibration exercise is a
      crucial step in cross-sectional epidemiological surveys, and the kappa test
      calculated on a tooth-by-tooth basis is the appropriate measurement to test
      agreement between examiners for dental caries.

PMID- 11241939
TI  - [Policy-making tiers of the Unified Health System (SUS) in the State of Rio de
      Janeiro and the decision-making process].
AB  - The literature concerning governmental policy-making generally encompasses the
      entire policy-making field. This study focused on one particular aspect of this
      process in the State of Rio de Janeiro, from January 1998 to July 1999: the
      formal decision-making tiers represented by State Health Council (CES) and the
      Bipartite Inter-Managerial Commission (CIB), as well as the relationships between
      these councils and the State Health Secretariat (SES), which holds political
      responsibility for approving or rejecting decisions and is thus a key player in
      the implementation of the Unified Health System (SUS) at the State level. Despite
      the political confrontation among the SES, CIB, and CES, we have observed that
      the new design in health policy vis-a-vis the decision-making process has
      fostered increasing influence by social actors involved in decisions and that the
      negotiated arrangements, although the result of a given correlation of forces,
      have favored the democratization of policy-making in the health sector.

PMID- 11241940
TI  - [Gender and cutaneous leishmaniasis in Colombia].
AB  - Leishmaniasis in Colombia has traditionally been seen as a health risk for adult
      males, as they become infected when they enter the vector's biotopes to tap
      natural resources. National health statistics seem to confirm this theory.
      However, during field studies, the Program for the Study and Control of Tropical
      Diseases (PECET) observed both equal proportions of men and women with active
      leishmaniasis and delayed hypersensitivity skin tests and equal proportions of
      males and females having had contact with the parasite from early childhood.
      Several factors that have not been analyzed in depth in Colombia thus far appear
      to distort the disease's epidemiological pattern in the country, and gender
      linked differences in access to health care appear to exist. As a consequence, no
      relief is provided for this source of human suffering, and socioeconomic
      repercussions for households are significant. Preventive measures by the
      Colombian Ministry of Health (MOH) systematically underestimate the magnitude of
      intra- and peridomiciliary transmission, and female patients are excluded from
      active case detection. Further research should be devoted to this phenomenon. The
      MOH should be encouraged to improve leishmaniasis control programs, especially
      with regard to active case detection, training, and teaching, so that quicker
      diagnosis can be performed. Meanwhile, the MOH should retrain its health
      personnel.

PMID- 11241941
TI  - [Occupational activity and prevalence of osteomuscular pain among dentists in
      Belo Horizonte, Minas Gerais State, Brazil: a contribution to the debate on work
      related musculoskeletal disorders].
AB  - The objective was to determine the prevalence of upper-limb and back pain among
      dentists (n = 358) and factors associated with these symptoms. Dentists were
      interviewed using a self-administered questionnaire containing data on
      sociodemographic, occupational, lifestyle, and psychosocial factors and presence,
      site, and characteristics of pain. Participation rate was 92.3%. 58% reported
      upper limb pain, with 22, 21, 20, and 17% for the arm, back, neck, and shoulder,
      respectively. 26% reported daily frequency and 40% classified pain as moderate or
      severe. In the multivariate analysis (multiple logistic regression), the factors
      associated with pain were: neck: anxiety/depression (OR = 2.3; CI95%: 1.2-4.5),
      compressor in the office (OR = 2.1; CI95%: 1.2-3.7), job satisfaction (OR = 0.3;
      CI95%: 0.1-0.9), and use of indirect vision (OR = 0.5; CI95%: 0.3-0.9); shoulder:
      income > 20 minimum wage (OR = 2.9; CI95%: 1.2-6.7), greater productivity (OR =
      3.3; CI95%: 1.3-8.4), height > or = 160cm (OR = 0.3; CI95%: 0.2-0.7), and age 30
      49 years (OR = 0.3; CI95%: 0.1-0.8); back: anxiety/depression (OR = 2.3; CI95%:
      1.2-4.5), manual activity (OR = 0.4; CI95%: 0.2-0.9), and being married (OR =
      0.5; CI95%: 0.3-0.9); arms: manual activity (OR = 1.8; CI95%: 1.0-3.2).

PMID- 11241943
TI  - [Dr. Sackett & "Mr. Sacketeer"... Enchantment and disenchantment in the land of
      expertise in evidence-based medicine].
AB  - In May 2000, Prof. David L. Sackett, one of the founders of the evidence-based
      medicine movement (EBM), published an article in the British Medical Journal in
      which he renounced writing, teaching, or serving as a referee for topics related
      to EBM. He justified his stance based on his frustration over what he considered
      the harmful effects of an alleged excess of experts in this field. Sackett's
      position was the raw material whereby we approached aspects linked to the
      definition and scope of EBM as well as related critiques. We also stress the
      movement's various rhetorical strategies. In addition, we discuss both the notion
      of expertise and the role of "expert systems" and "specialized competence" in our
      societal milieu, developed respectively by Anthony Giddens and Zygmunt Bauman.
      The main focus of this commentary is to emphasize that while we are dealing with
      a progressive trend towards acquiring control and intelligibility vis-a-vis the
      objects of our research, we must consider the possibility of dimensions that
      cannot be reached by way of the rationalistic Western mode of thought.

PMID- 11241942
TI  - [Limitations and alternatives to the implementation of a program for drug users
      at risk of HIV infection using the Social Network Approach].
AB  - The authors describe the development of a preventive program focused on
      intravenous drug users at risk of HIV infection, using the Social Network
      Approach as the intervention model. The authors describe the project's steps in a
      large university hospital in southern Brazil, emphasizing the unique methods and
      techniques developed by the treatment staff. Problems encountered during the
      project development are discussed, aimed at identifying the reasons why the
      program only achieved partial success. The authors identify critical issues, such
      as the use of a new technique not previously tried in Brazil, difficulties in
      maintaining IV drug users in treatment, lack of infrastructure for walk-in
      treatment, and the challenge of motivating staff and patients to continue
      treatment. The authors conclude by listing suggestions aimed at facilitating the
      development of new projects based on the same conceptual model.

PMID- 11241944
TI  - [Frontiers of anthropological research: ethics, autonomy, and trafficking in
      human organs. A commentary on The Global Traffic in Human Organs, by Nancy
      Scheper-Hughes].
AB  - The bioethical debate over the commercialization of the human body has
      intensified in recent years. This article discusses the principles of ethics and
      autonomy in the most important ethnography on international traffic in human
      organs, coordinated by anthropologist Nancy Scheper-Hughes. The author discusses
      how defending the ethics of non-commercialization of the human body entails
      absolute ethical principles pertaining to human life, a political premise whose
      legitimacy is not recognized by relativist anthropologists.

PMID- 11241945
TI  - [Hourly frequency and seasonality of Lutzomyia longipalpis (Diptera: Psychodidae:
      Phlebotominae) on Sao Luis Island, Maranhao, Brazil].
AB  - This article presents the hourly and seasonal distribution of the Lutzomyia
      longipalpis sand fly captured on Sao Luis Island, Maranhao State. A total of
      11,200 specimens were captured during monthly use of CDC light traps indoors and
      in animal sheds, between 6:00 PM and 6:00 AM, in 1996 and 1997. The sand fly
      behaved as an annual species, with a high frequency year-round, while it was most
      abundant during the rainy season (57.2%) as compared to the dry season (42.8%).
      The highest frequencies during the rainy season occurred in January and April and
      in the dry season in July and November. The species was found all night long,
      mainly between 6:00 PM and 10:00 PM in animal sheds and between 8:00 PM and 2:00
      AM indoors.

PMID- 11241946
TI  - [Digestive tract microbiota in female Lutzomyia longipalpis (Lutz & Neiva, 1912)
      (Diptera: Psychodidae) from colonies feeding on blood meal and sucrose plus blood
      meal].
AB  - There are very few reports on the microbiota of the digestive tract of sand
      flies, an important omission considering that blood is not the only meal
      ingested. Male and female sand flies obtain sugar meals from several sources,
      thereby increasing their chance of infection with microorganisms. Chances of
      contamination are higher when insects are bred in the laboratory, and this may
      affect the development of Leishmania spp. From the digestive tract of 300 sand
      fly females separated in two groups we isolated 10 species of bacteria in group 1
      and 8 species in group 2. In group 1, Enterobacteriaceae of the following genera
      were identified: Serratia, Enterobacter, and Yokenella and the non-fermenters:
      Pseudomonas, Acinetobacter, and Stenotrophomonas. In group 2, the
      Enterobacteriaceae Enterobacter and Serratia were identified as well as the non
      fermenters Acinetobacter, Stenotrophomonas, Burkolderia, and Pseudomonas.

PMID- 11241947
TI  - [Collective health: a challenge for nursing].
AB  - This study takes public health as the point of departure to discuss both the
      concept of collective health and its object and field of action, emphasizing the
      concepts of man, collective and individual spheres, and health-disease, through a
      discussion of the interdisciplinary construction of the collective health field.
      The authors then place nursing within this field, emphasizing what appears to be
      the greatest challenge, i.e., to approach nursing as a practice of relationships.

PMID- 11241951
TI  - Enzymatic analysis in Anopheles nuneztovari Gabaldon (Diptera, Culicidae).
AB  - Enzymatic analysis in Anopheles nuneztovari was made using four populations from
      the Brazilian Amazon and two from Colombia. The enzymes ME and XDH presented a
      monomorphic locus in all of the studied populations. EST and LAP presented a
      higher number of loci. In EST, genetic variation was observed in the five loci;
      LAP presented four loci, with allec variation in two loci. In IDH, three activity
      regions were stained, with genetic variation for locus Idh-1 in the Brazilian
      Amazon populations. A locus for MDH was observed, with genetic variation in the
      six populations. A region was verified for ACON, with four alleles in Sitronela
      and three in the other populations. PGM constituted one locus, with a high
      variability in the Brazilian Amazon populations. A locus was observed for 6-PGD
      with allelic variation in all of the populations with the exception of Tibu.
      Enzyme PGI presented two loci, both with genetic variability in the Tucurui
      population. The enzyme alpha-GPD showed an activity region with polymorphism in
      the Tucurui, Tibu and Sitronela populations. The phenotypic variations detected
      for these enzymes suggest that four (EST, LAP, ACON and PGM) possess monomeric
      structures and five (IDH, MDH, 6-PGD, PGI and alpha-GPD) dimeric structures in
      their proteins. These enzymes constitute in important markers to estimate
      variability and genetic divergence in natural populations of A. nuneztovari.

PMID- 11241952
TI  - Comparative phytosociology of tree sinusiae between contiguous forests in
      different stages of succession.
AB  - The Baturite Mountain Range, located in the State of Ceara (BRA), displays on its
      highest levels a vegetation viewed as a disjunction from the Atlantic Forest in
      the East of Brazil. Among the various attributes associated with this vegetation,
      the abundance of water resources and a high biodiversity have a more outstanding
      relevance. However, in view of the current accelerated deforestation process,
      those attributes may be threatened in a near future. Therefore, the present work
      is a comparative study with its focus on vegetal community organization (tree
      sinusiae) and the floristic similarity and the phytodiversity of two areas in
      different successive stages, preserved and deforested 24 years ago. The aim of
      that intent was to obtain information that could essentially shed light on the
      deforestation effects on tree vegetation and which could suggest scientific
      support regarding urgent projects of habitat reconstruction. The methodology used
      folowed the model utilized for rain forest, i.e. consisting of a random
      distribution of 10 x 20 m plots surveying the living woody species with DBH >/= 5
      cm. The results obtained suggest that a possible new physiognomy type is emerging
      on the Baturite Mountain Range because of deforestation. The Myrtaceae and
      Mimosaceae families were the ones that contributed most significantly to species
      richness, being the most outstanding for Areas 1 and 2, respectively. The
      deforestation which occurred in Area 2 eliminated 28 species and gave birth to a
      current densely distinct floristic composition.

PMID- 11241954
TI  - Mercury content in shark species from the South-Eastern Brazilian coast.
AB  - We present here the first results of Hg concentrations in three small shark
      species (Rhizoprionodon lalandei, R. porosus and Mustelus higmani) from the SE
      Brazilian coast. Mercury concentrations in R. lalandei ranged from 21.5 to 280.0
      ng.g-1 dry weight (d.w.) (average 74.6 ng.g-1 d.w.; 17.9 ng.g-1 wet weight). In
      R. porosus, concentrations ranged from 7.6 to 90.5 ng.g-1 d.w. (average 42.2 ng.g
      1 d.w., 9.4 ng.g-1 wet weight), whereas in M. higmani, concentrations ranged from
      13.0 to 162.8 ng.g-1 d.w. (average 54.9 ng.g-1 d.w., 13.4 ng.g-1 wet weight).
      These concentration ranges are very low compared with values reported for other
      large shark species of the Southwestern Atlantic Ocean. There was a significant
      positive correlation between Hg concentrations and individual size, suggesting
      that biomagnification is occurring in these animals.

PMID- 11241955
TI  - Aspects of the ecology of proteocephalid cestodes parasites of Sorubim lima
      (Pimelodidae) of the upper Parana River, Brazil: I. Structure and influence of
      host's size and sex.
AB  - Between March 1992 and February 1996, 107 specimens of Sorubim lima were
      collected in the floodplain of the upper Parana river. Ninety-five (88.78%)
      specimens were parasitized with at least one species of proteocephalid cestodes.
      7,573 specimens of four different species were collected (average intensity 79.71
      parasites/host): Paramonticellia itaipuensis Pavanelli & Rego, 1991; Nupelia
      portoriquensis Pavanelli & Rego, 1991; Spatulifer maringaensis Pavanelli & Rego,
      1989 and Spasskyellina spinulifera Woodland, 1935. S. maringaensis was the most
      prevalent and abundant. There were three dominant species P. itaipuensis, S.
      maringaensis and N. portoriquensis) and one co-dominant species (S. spinulifera).
      The three environments (lotic, semilotic and lentic) in which collection was
      undertaken showed high similarity with regard to parasitic fauna. A high Simpson
      index value (0.359) indicates dominance tendency among species of parasites.
      Concerning S. maringaensis significant positive correlation was observed between
      parasite intensity and standard length of hosts. No species had negative
      correlation. With regard to S. maringaensis and N. portoriquensis prevalence was
      positive and significantly correlated with standard length of hosts. No species
      had negative correlation. In the case of S. maringaensis and N. portoriquensis
      influence of host's sex was noted on parasite intensity. There was no sex
      influence on parasite prevalence in any species.

PMID- 11241956
TI  - Aspects of the ecology of proteocephalid cestodes, parasites of Sorubim lima
      (Pimelodidae), of the upper Parana River, Brazil: II. Interspecific associations
      and distribution of gastrintestinal parasites.
AB  - One hundred and seven specimens of Sorubim lima (Bloch & Schneider, 1801) were
      collected in the floodplain of the upper Parana River, Brazil between March 1992
      and February 1996. Ninety-five specimens (88.78%) were parasited by at least a
      species of proteocephalid cestode. 7,573 parasites specimens of four different
      species were collected (average intensity 79.71 parasites/host): Paramonticellia
      itaipuensis Pavanelli & Rego, 1991; Nupelia portoriquensis Pavanelli & Rego,
      1991; Spatulifer maringaensis Pavanelli & Rego, 1989 and Spasskyellina
      spinulifera (Woodland, 1935). The two most prevalent species, Spatulifer
      maringaensis and Paramonticellia itaipuensis, were parasiting the entire
      gastrointestinal tract. Nupelia portoriquensis parasited only the anterior and
      posterior intestine of the host.

PMID- 11241957
TI  - Feeding habits of Chaoboridae larvae in a tropical Brazilian reservoir.
AB  - The diet of the four larval instars of a Chaoboridae species of Lake Monte
      Alegre, was evaluated through the analysis of the crop content of individuals
      caught at night in the lake. Peridinium and zooflagellates were the major
      components of the diet of instars I and II, whereas microcrustaceans, especially
      the cladoceran Bosmina, were most important for late instars. When the
      preferential prey decreased, in the course of the year, the diet was more
      diversified, increasing the ingestion of Peridinium by instars III and IV. There
      is a relationship between the mouth diameter of the larvae and the maximum width,
      height, or diameter of the ingested organisms.

PMID- 11241960
TI  - Prediction of colonization by macrophytes in the Yacireta reservoir of the Parana
      River (Argentina and Paraguay).
AB  - The potential colonization by anchored plants (PCAP) and the potential areas for
      initial colonization of free floating plants were estimated during the early
      filling phase for the Yacireta reservoir. In order to obtain the PCAP, the
      observed maximum depth of colonization of the anchored macrophytes before
      impoundment and the hypsographic curves were used. The species inhabiting the pre
      impoundment area were classified according to the different bioforms before the
      inclussion in the analysis. The areal extent of PCAP (from depths between 0-4 m)
      could reach 275 km2 at 76 m above sea level (current water level), whereas at 82
      m above sea level (final filling level) the littoral zone will be increased by
      about 21.5%. The potential area for geophytes was estimated to be 99 km2; 131 km2
      for root-floating leaved plants and 120 km2 for submerged plants, at 76 m above
      sea level. At 82 m above sea level, the geophytes could reach 271 km2. The data
      for wind frequency, velocity and fetch, together with depth were used to
      calculate shallow and sheltered areas in which free floating plants could find
      favourable conditions to initial colonization. Physical and chemical features
      recorded at eight stations during the early filling phase are discussed in
      relation to potential plant development.

PMID- 11241958
TI  - Seasonal variation of nutrients and energy in tambaqui's (Colossoma Macropomum
      Cuvier, 1818) natural food.
AB  - The aim of this study was to evaluate the importance of fruits and seeds as food
      items in the natural diet of the tambaqui (Colossoma macropomum). During one
      year, tambaqui's stomach contents were collected, and their nutritional and
      energetic values were determined. During the flooding period, and while the river
      water was rising, which coincided with a high availability of fruits and seeds,
      the protein content of food was low (11%-15% of dry matter basis), whereas in the
      dry season, when tambaqui fed mainly zooplankton, there was a high protein
      content (45%-57% of dry matter basis). Lipid, carbohydrate, crude fiber, ash and
      gross energy contents of the diet varied depending on the river water level and
      the food items ingested.

PMID- 11241961
TI  - The ichthyofauna of the marginal lagoons of the Sorocaba River, SP, Brazil:
      composition, abundance and effect of the anthropogenic actions.
AB  - The marginal lagoons of the Sorocaba River fulfil important functions in their
      lotic ecosystems and for its fish communities, providing shelter, food, and area
      for fish early stages of development. The lagoons are also an escape from the
      river pollution since the physical-chemical characteristics of their water are
      more stable than the river water. Nevertheless, these lagoons are under a series
      of impacts that contribute to reduce their diversity and stability such as water
      pollution, deforesting and river dumping. These impacts decrease habitat
      availability, and modify the fish community structure by reducing the number of
      species in the Sorocaba River, the floodplains and its marginal lagoons.

PMID- 11241962
TI  - New record of planktonic cladoceran to the upper Parana River, Brazil: Bosmina
      huaroensis Delachaux, 1918.
AB  - In this paper we register the first occurrence of Bosmina huaroensis Delachaux,
      1918 in the upper Parana River basin, which is probably the first record to
      Brazil. Illustrations and an updated description of the species are given.

PMID- 11241963
TI  - Population dynamics of Pseudomonas sp. along a spatial gradient of phosphate: an
      experimental approach for spatial ecology.
AB  - Many theoretical models have been proposed to study the effect of space on
      population dynamics and interactions, but most of them are difficult to translate
      into experimental setups due to their abstract nature. Here we defend the
      gradostat as a valuable experimental tool for testing such theories. The
      gradostat is a culture system with bi-directional flow that forms nutrient
      gradients at steady state. In this study, we use a 3-vessel gradostat with a
      phosphate gradient to study the effect of spatial heterogeneity on the spatial
      distribution of Pseudomonas sp., an heterotrophic aquatic bacterium. The observed
      distributions partially agree with theoretical predictions, obtained from a
      mathematical model.

PMID- 11241964
TI  - Feed training of peacock bass (Cichla sp.).
AB  - The Amazonian cichlid peacock bass (Cichla sp.) is a highly marketable food and
      sport fish, therefore a suitable species for aquaculture. However, because of its
      piscivorous feeding preferences, the species does not accept dry feeds
      voluntarily, turning its intensive culture difficult and costly. This study aimed
      to wean fingerling peacock bass from inert moist food to dry diets. In a first
      experiment, 1,134 fingerlings weighting 0.27 g were divided in two 0.37 m3 hapas
      and fed ground fish flesh with 35% success. Then, 1.3 g fish were pooled, stocked
      in six 25 L cages and fed two pellet sequences with 80%, 60%, 40%, 20% and 0%
      ground fish flesh (GFF). One sequence was flavored with 10% krill meal (Euphausia
      sp.). Training success of fish fed the GFF-00 diet flavored with krill reached
      12%a compared to 11.6%a (p < 0.05) for diets without krill meal. A second
      experiment was set up with 969, 1.5 g fish, trained with GFF with 39.8% success.
      After the feed training period, 2.2 g fish were then fed a sequence of moist
      pellets containing 80%, 60% and 45% GFF. Fish trained to feed on moist pellets
      with 45% ground fish were pooled and stocked into nine 25 L cages. Fish were
      weaned to dry pellets without ground fish flesh (GFF-00) using three diet
      sequences: 1) dry pellets; 2) moist pellets; and 3) dry pellets flavored with 4%
      cod liver oil; all three diets contained 30, 10 and 0% GFF. The three sequences
      yielded, respectively 30.8%a, 23.6%a, and 24.7%a (p < 0.05) fish feeding on GFF
      00. There were no apparent beneficial effects of increasing moisture or addition
      of cod liver oil as flavor enhancers in the weaning diets. This study revealed
      the feasibility of training peacock bass to accept dry pellets, but feeding young
      fish ground fish flesh seemed to be a major bottleneck in improving feed training
      success.

PMID- 11241965
TI  - Nesting behavior of the swallow-tailed hummingbird, Eupetomena macroura
      (Trochilidae, Aves).
AB  - An August or winter nestling of Eupetomena macroura was fed only every 40-50 min
      for at least 24 days in the nest, with fewer feedings at midday. As in other
      hummingbirds, it was brooded only the first week or two, and left alone even on
      cool nights after 12 days, probably due to the small nest size. The female
      attacked birds of many non-nectarivore species near the nest, in part probably to
      avoid predation. Botfly parasitism was extremely high, as in some other forest
      edge birds.

PMID- 11241966
TI  - Nesting behavior of the Picazuro pigeon, Columba Picazuro (Columbidae, Aves).
AB  - The Picazuro Pigeon nests in all months of the year in southeastern Brazil. Nest
      material is plucked from trees or ground and carried to build a frail and
      transparent nest of sticks where one egg is laid. Female and male alternate in
      incubation and brooding and do not soil the nest with feces.

PMID- 11241967
TI  - Parental care in the buffy-tufted-ear marmoset (Callithrix aurita) in wild and
      captive groups.
AB  - Studies on cooperative care of offspring in callitrichid primates are biased in
      favor of observations in captivity. In the wild, however, individuals have to
      deal with environmental pressures, which may influence their social behavior. We
      compared the individual effort attributed to parental care offered by members of
      a wild group (couple, plus a subadult helper) and two captive groups (A: couple,
      plus an subadult helper, B: couple, plus four adult helpers) of the buffy-tufted
      ear marmoset, Callithrix aurita, from weeks 1-12 after the infants' birth. The
      carrier (breeding male and female or helper) and the infant's feeding (food
      sharing and foraging for food) were recorded. Up to week four, while the wild
      breeding pair shared infant carrying at similar proportions, the male from
      captive group A carried 100% of the time. Adult helpers from group B were the
      main carriers. Carrying behavior extended up to week 12 only in the wild group.
      Food provisioning to the infant was observed earlier in the groups wild and A,
      but general proportion of feeding records was lower in the wild than in
      captivity. Energetic cost of travelling and searching for food may be associated
      with equal division of carrying behavior by the wild breeding pair. Higher
      proportions of carrying in the groups wild and B may have delayed the development
      of the infants' motor skills required in foraging. Our data agree with previous
      studies: the father's lower investment in carrying when adult helpers are present
      and lower contribution of subadult non-reproductive members.

PMID- 11241968
TI  - Recent Studies on Neoechinorhynchus curemai Noronha, 1973 (Acanthocephala:
      Neoechinorhynchidae), in Prochilodus lineatus Valenciennes, 1836, from Volta
      Grande Reservoir, MG, Brazil.
AB  - The present work described helminth parasites of curimbata, Prochilodus lineatus
      Valenciennes, 1836 from Volta Grande Reservoir, MG, Brazil. Eighteen fishes with
      average 46.7 +/- 1.1 cm length and 1,674.8 +/- 75.6 g weight were collected. Of
      the analysed fishes, 15 were parasitized with acanthocephalans in the intestine,
      showing a prevalence of 83.3%. The helminth was identified as Neoechinorhynchus
      curemai Noronha, 1973 (Acanthocephala: Neoechinorhynchidae). It differs from
      other species in dimension of characters and morphology. From the original
      description of N. curemai, it differs from the biggest dimension of testis,
      elongated cement gland, nucleated lemnisci, eggs size, larger proboscis hooks
      length in the middle and in the third circle in males and larger hooks in the
      anterior circle in females. A smaller percentage occupied by the reproductive
      system in female trunk was reported. The observation of paratypes of N. curemai
      of Noronha (1973) showed a great similarity with those of the present work. This
      fact complements the helminth description from elsewhere.

PMID- 11241969
TI  - Deladenus siricidicola, bedding (Neotylenchidae) parasitism evaluation in adult
      Sirex noctilio, Fabricius, 1793 (Hymenoptera: Siricidae).
AB  - This work aimed to evaluate the Deladenus siricidicola, Bedding (Neotylenchidae)
      parasitism in adults Sirex noctilio, Fabricius, 1793 (Hymenoptera: Siricidae).
      Timber was sampled by cutting out pieces of 0.80 m in length in Sirex noctilio
      attacked and Deladenus siricidicola inoculated Pinus taeda. Longs were 15-20 cm
      in diameter, according to the tree age. Samples were packed in gauze-cages, for
      daily observations, till S. noctilio adults emergence. The emerged insects were
      transported, in plastic containers to the laboratory, where they were sectioned
      and dissected under stereoscopic microscopy to observ the nematode occurrence.
      From the initially proposed ten units, nine of them were evaluated in a total of
      1,810 emerged adult insects, being 1,441 males and 369 females. Nematode
      parasitism was shown in 267 males and 74 females, in a total of 341 infected
      insects (18.84%).

PMID- 11241970
TI  - Comparative analysis of cranial suture complexity in the genus Caiman
      (Crocodylia, Alligatoridae).
AB  - The variation in degrees of interdigitation (complexity) in cranial sutures among
      species of Caiman in different skull regions was studied by fractal analysis. Our
      findings show that there is a small species effect in the fractal dimension of
      cranial sutures, but most variation is accounted for by regional differentiation
      within the skull. There is also a significant interaction between species and
      cranial regions. The braincase sutures show higher fractal dimension than the
      facial skull sutures for all three species. The fractal dimension of nasal
      maxilla suture is larger in Caiman latirostris than in the other species. The
      braincase sutures show higher fractal dimensions in C. sclerops than in the other
      species. The results suggest that different regions of the skull in caimans are
      under differential functional stress and the braincase sutures must counteract
      stronger disarticulation forces than the facial sutures. The larger fractal
      dimension shown by C. latirostris in facial sutures has probably a functional
      basis also. Caiman latirostris is known to have preferences for harder food items
      than the other species.

PMID- 11241971
TI  - Diet of the colubrid snake, Thamnodynastes strigatus (Gunther, 1858) from Parana
      State, Brazil, with field notes on anuran predation.
AB  - Dissection of 44 specimens of the colubrid snake Thamnodynastes strigatus
      (Serpentes: Colubridae) provided data on food habits. Prey items include frogs
      (71.4% of the sample), rodents (14.3%), fishes (10.7%), and lizards (3.6%). The
      most of the anuran species recorded (Bufo sp., Leptodactylus sp., Physalaemus
      cuvieri and Scinax fuscovarius) are ground dwellers or call at the water level.
      Field observations provided information on the feeding behavior.

PMID- 11241972
TI  - Morphology and anatomy of developing fruits and seeds of Mammea americana L.
      (Clusiaceae).
AB  - Morphological, structural and developmental features of fruits and seeds of
      Mammea americana L. are here studied, with the purpose to give a proper
      classification of their fruit and embryo type and to contribute to future
      taxonomical and ecological studies. The fruit is a berry and the "rind" consists
      of the exocarp, represented by a periderm with lenticels, and by the
      parenchymatic mesocarp, with branched secretory ducts and vascular bundles. The
      edible pulpy is formed by the endocarp, destituted of secretory ducts, and
      derived from the activity of a ventral meristem, which emerges early in the fruit
      development. The inner endocarp cell layers undergo a radial elongation and
      become firmly attached to the testal outer layers. At maturation the endocarp may
      be released from the rest of the pericarp. The ovules are unitegmic and they turn
      into unitegmic and exalbuminous seeds. The multiseriate testa consists of thick
      walled cells and sclerenchymatous fibers. This last features have carried out to
      a wrong interpretation that the fruit of this species is a drupe. The embryo is
      pseudo-conferruminate, with two massive foodstoring cotyledons, rich in starch,
      firmly attached.

PMID- 11241973
TI  - Marine leech, Stibarobdella macrothela (Schmarda, 1861) (Hirudinea,
      piscicolidae), parasitic on the whaler shark, Carcharhinus Brachyurus (Gunther,
      1870) (Chondrichthyes, Carcharhinidae), in Southern Brazilian waters.
AB  - The presence of the sea leech, Stibarobdella macrothela (Schmarda, 1861)
      (Hirudinea, Piscicolidae), is marked in the south coast of Brazil, based on the
      single specimen with 67 mm (CT), collected in the intergill ventral region of a
      whaler shark, Carcharhinus brachyurus (Gunther, 1870) (Chondrichtyes,
      Carcharhinidae), adult male with about 2 m (CT), being treated of the first
      registrations of S. macrothela in the Southwest Atlantic and the parasitic
      association with C. brachyurus.

PMID- 11241975
TI  - Patents in a genetic age.

PMID- 11241976
TI  - The road to the code.and the cast who brought genetics to centre stage.

PMID- 11241977
TI  - Affairs of the heartless.

PMID- 11241978
TI  - An excavation of the drug myth.

PMID- 11241979
TI  - One who created a tempo of his own.

PMID- 11241980
TI  - Channel fault in osteopetrosis.

PMID- 11241982
TI  - Erratum: Watching fights raises fish hormone levels.

PMID- 11241981
TI  - Obituary: Konrad E. Bloch (1912-2000).

PMID- 11241983
TI  - Everyone's genome.

PMID- 11241984
TI  - Genome speak.

PMID- 11241985
TI  - Microarrays, DNA and RNA prep.

PMID- 11241987
TI  - Biology moves into the silicon stage.

PMID- 11241986
TI  - Tips for sequence centre job-seekers.

PMID- 11241989
TI  - In search of unity.

PMID- 11241990
TI  - Art in the plastic age.

PMID- 11241991
TI  - From the monastery to the laboratory.

PMID- 11241992
TI  - Corruption and its consequences.

PMID- 11241993
TI  - Correction:

PMID- 11241994
TI  - Obituary: Tom Kilburn (1921-2001).

PMID- 11241995
TI  - Astrobiology.

PMID- 11241996
TI  - Senescence and cell death.

PMID- 11241997
TI  - China's hopes and hypes.

PMID- 11241998
TI  - Bush declines to support drug companies' line on AIDS profits.

PMID- 11241999
TI  - Growers cotton on to GM bollworm.

PMID- 11242000
TI  - Farmers act to avert foot-and-mouth crisis.

PMID- 11242001
TI  - Europe frames fresh funding initiative for research.

PMID- 11242002
TI  - GlaxoSmithKline pushes its labs towards 'biotech' future.

PMID- 11242003
TI  - Hepatitis pioneer takes the reins for French medicine.

PMID- 11242004
TI  - Benefits of low-tar smokes just a pipe dream.

PMID- 11242005
TI  - Museum suffers spiritual cramps over Mendel's work.

PMID- 11242006
TI  - Goal-directed revamp for Japanese research.

PMID- 11242007
TI  - Israel seeks sweet smell of success.

PMID- 11242009
TI  - Correction:

PMID- 11242010
TI  - Chinese biology. A great leap forward.

PMID- 11242011
TI  - Politics, ethics and collaborations.

PMID- 11242012
TI  - Breaking the mould.

PMID- 11242013
TI  - All sectors of society must work together to save biodiversity.

PMID- 11242015
TI  - Highlighting the grey matter.

PMID- 11242014
TI  - High rate of inbreeding in Spanish universities.

PMID- 11242016
TI  - The real benefits of copycats.

PMID- 11242017
TI  - Evolutionary celebrities.

PMID- 11242018
TI  - Science in culture.

PMID- 11242019
TI  - Character-building.

PMID- 11242020
TI  - Perceptions of knowledge.

PMID- 11242021
TI  - Superconductivity. Genie in a bottle.

PMID- 11242022
TI  - An attractive force in metastasis.

PMID- 11242024
TI  - 100 and 50 years ago.

PMID- 11242023
TI  - Icing Ganymede.

PMID- 11242025
TI  - Particle physics. Precision precession.

PMID- 11242026
TI  - A big development for a small RNA.

PMID- 11242027
TI  - Animal husbandry. Assessing the welfare state.

PMID- 11242028
TI  - Materials scienceAll chopped up.

PMID- 11242029
TI  - Condensed matter. Memories of paste.

PMID- 11242030
TI  - Apoptosis. Baiting death inhibitors.

PMID- 11242031
TI  - Frustrations of fur-farmed mink.

PMID- 11242032
TI  - Structural colour. Now you see it--now you don't.

PMID- 11242033
TI  - erratum: A viable herd of genetically uniform cattle.

PMID- 11242034
TI  - Mammalian MAP kinase signalling cascades.
AB  - Mitogen-activated protein kinases (MAPKs) are important signal transducing
      enzymes, unique to eukaryotes, that are involved in many facets of cellular
      regulation. Initial research concentrated on defining the components and
      organization of MAPK signalling cascades, but recent studies have begun to shed
      light on the physiological functions of these cascades in the control of gene
      expression, cell proliferation and programmed cell death.

PMID- 11242035
TI  - Synaptotagmin I functions as a calcium regulator of release probability.
AB  - In all synapses, Ca2+ triggers neurotransmitter release to initiate signal
      transmission. Ca2+ presumably acts by activating synaptic Ca2+ sensors, but the
      nature of these sensors--which are the gatekeepers to neurotransmission--remains
      unclear. One of the candidate Ca2+ sensors in release is the synaptic Ca2+
      binding protein synaptotagmin I. Here we have studied a point mutation in
      synaptotagmin I that causes a twofold decrease in overall Ca2+ affinity without
      inducing structural or conformational changes. When introduced by homologous
      recombination into the endogenous synaptotagmin I gene in mice, this point
      mutation decreases the Ca2+ sensitivity of neurotransmitter release twofold, but
      does not alter spontaneous release or the size of the readily releasable pool of
      neurotransmitters. Therefore, Ca2+ binding to synaptotagmin I participates in
      triggering neurotransmitter release at the synapse.

PMID- 11242037
TI  - Flooding of Ganymede's bright terrains by low-viscosity water-ice lavas.
AB  - Large regions of the jovian moon Ganymede have been resurfaced, but the means has
      been unclear. Suggestions have ranged from volcanic eruptions of liquid water or
      solid ice to tectonic deformation, but definitive high-resolution morphological
      evidence has been lacking. Here we report digital elevation models of parts of
      the surface of Ganymede, derived from stereo pairs combining data from the
      Voyager and Galileo spacecraft, which reveal bright, smooth terrains that lie at
      roughly constant elevations 100 to 1,000 metres below the surrounding rougher
      terrains. These topographic data, together with new images that show fine-scale
      embayment and burial of older features, indicate that the smooth terrains were
      formed by flooding of shallow structural troughs by low-viscosity water-ice
      lavas. The oldest and most deformed areas (the 'reticulate' terrains) in general
      have the highest relative elevations, whereas units of the most common resurfaced
      type--the grooved terrain--lie at elevations between those of the smooth and
      reticulate terrains. Bright terrain, which accounts for some two-thirds of the
      surface, probably results from a continuum of processes, including crustal
      rifting, shallow flooding and groove formation. Volcanism plays an integral role
      in these processes, and is consistent with partial melting of Ganymede's
      interior.

PMID- 11242036
TI  - Involvement of chemokine receptors in breast cancer metastasis.
AB  - Breast cancer is characterized by a distinct metastatic pattern involving the
      regional lymph nodes, bone marrow, lung and liver. Tumour cell migration and
      metastasis share many similarities with leukocyte trafficking, which is
      critically regulated by chemokines and their receptors. Here we report that the
      chemokine receptors CXCR4 and CCR7 are highly expressed in human breast cancer
      cells, malignant breast tumours and metastases. Their respective ligands
      CXCL12/SDF-1alpha and CCL21/6Ckine exhibit peak levels of expression in organs
      representing the first destinations of breast cancer metastasis. In breast cancer
      cells, signalling through CXCR4 or CCR7 mediates actin polymerization and
      pseudopodia formation, and subsequently induces chemotactic and invasive
      responses. In vivo, neutralizing the interactions of CXCL12/CXCR4 significantly
      impairs metastasis of breast cancer cells to regional lymph nodes and lung.
      Malignant melanoma, which has a similar metastatic pattern as breast cancer but
      also a high incidence of skin metastases, shows high expression levels of CCR10
      in addition to CXCR4 and CCR7. Our findings indicate that chemokines and their
      receptors have a critical role in determining the metastatic destination of
      tumour cells.

PMID- 11242038
TI  - Coherent manipulation of semiconductor quantum bits with terahertz radiation.
AB  - Quantum bits (qubits) are the fundamental building blocks of quantum information
      processors, such as quantum computers. A qubit comprises a pair of well
      characterized quantum states that can in principle be manipulated quickly
      compared to the time it takes them to decohere by coupling to their environment.
      Much remains to be understood about the manipulation and decoherence of
      semiconductor qubits. Here we show that hydrogen-atom-like motional states of
      electrons bound to donor impurities in currently available semiconductors can
      serve as model qubits. We use intense pulses of terahertz radiation to induce
      coherent, damped Rabi oscillations in the population of two low-lying states of
      donor impurities in GaAs. Our observations demonstrate that a quantum-confined
      extrinsic electron in a semiconductor can be coherently manipulated like an
      atomic electron, even while sharing space with approximately 10(5) atoms in its
      semiconductor host. We anticipate that this model system will be useful for
      measuring intrinsic decoherence processes, and for testing both simple and
      complex manipulations of semiconductor qubits.

PMID- 11242039
TI  - Superconductivity at 39 K in magnesium diboride.
AB  - In the light of the tremendous progress that has been made in raising the
      transition temperature of the copper oxide superconductors (for a review, see
      ref. 1), it is natural to wonder how high the transition temperature, Tc, can be
      pushed in other classes of materials. At present, the highest reported values of
      Tc for non-copper-oxide bulk superconductivity are 33 K in electron-doped
      Cs(x)Rb(y)C60 (ref. 2), and 30 K in Ba(1-x)K(x)BiO3 (ref. 3). (Hole-doped C60 was
      recently found to be superconducting with a Tc as high as 52 K, although the
      nature of the experiment meant that the supercurrents were confined to the
      surface of the C60 crystal, rather than probing the bulk.) Here we report the
      discovery of bulk superconductivity in magnesium diboride, MgB2. Magnetization
      and resistivity measurements establish a transition temperature of 39 K, which we
      believe to be the highest yet determined for a non-copper-oxide bulk
      superconductor.

PMID- 11242040
TI  - Non-thermal melting in semiconductors measured at femtosecond resolution.
AB  - Ultrafast time-resolved optical spectroscopy has revealed new classes of
      physical, chemical and biological reactions, in which directed, deterministic
      motions of atoms have a key role. This contrasts with the random, diffusive
      motion of atoms across activation barriers that typically determines kinetic
      rates on slower timescales. An example of these new processes is the ultrafast
      melting of semiconductors, which is believed to arise from a strong modification
      of the inter-atomic forces owing to laser-induced promotion of a large fraction
      (10% or more) of the valence electrons to the conduction band. The atoms
      immediately begin to move and rapidly gain sufficient kinetic energy to induce
      melting--much faster than the several picoseconds required to convert the
      electronic energy into thermal motions. Here we present measurements of the
      characteristic melting time of InSb with a recently developed technique of
      ultrafast time-resolved X-ray diffraction that, in contrast to optical
      spectroscopy, provides a direct probe of the changing atomic structure. The data
      establish unambiguously a loss of long-range order up to 900 A inside the
      crystal, with time constants as short as 350 femtoseconds. This ability to obtain
      the quantitative structural characterization of non-thermal processes should find
      widespread application in the study of ultrafast dynamics in other physical,
      chemical and biological systems.

PMID- 11242041
TI  - Propagating solitary waves along a rapidly moving crack front.
AB  - A rapidly moving crack in a brittle material is often idealized as a one
      dimensional object with a singular tip, moving through a two-dimensional
      material. However, in real three-dimensional materials, tensile cracks form a
      planar surface whose edge is a rapidly moving one-dimensional singular front. The
      dynamics of these fronts under repetitive interaction with material
      inhomogeneities (asperities) and the morphology of the fracture surface that they
      create are not yet understood. Here we show that perturbations to a crack front
      in a brittle material result in long-lived and highly localized waves, which we
      call 'front waves' These waves exhibit a unique characteristic shape and
      propagate along the crack front at approximately the Rayleigh wave speed (the
      speed of sound along a free surface). Following interaction, counter-propagating
      front waves retain both their shape and amplitude. They create characteristic
      traces along the fracture surface, providing cracks with both inertia and a new
      mode of dissipation. Front waves are intrinsically three-dimensional, and cannot
      exist in conventional two-dimensional theories of fracture. Because front waves
      can transport and distribute asperity-induced energy fluctuations throughout the
      crack front, they may help to explain how cracks remain a single coherent entity,
      despite repeated interactions with randomly dispersed asperities.

PMID- 11242042
TI  - Orbit-related long-term climate cycles revealed in a 12-Myr continental record
      from Lake Baikal.
AB  - Quaternary records of climate change from terrestrial sources, such as lake
      sediments and aeolian sediments, in general agree well with marine records. But
      continuous records that cover more than the past one million years were
      essentially unavailable until recently, when the high-sedimentation-rate site of
      Lake Baikal was exploited. Because of its location in the middle latitudes, Lake
      Baikal is highly sensitive to insolation changes and the entire lake remained
      uncovered by ice sheets throughout the Pleistocene epoch, making it a valuable
      archive for past climate. Here we examine long sediment cores from Lake Baikal
      that cover the past 12 million years. Our record reveals a gradual cooling of the
      Asian continental interior, with some fluctuations. Spectral analyses reveal
      periods of about 400 kyr, 600 kyr and 1,000 kyr, which may correspond to
      Milankovitch periods (reflecting orbital cycles). Our results indicate that
      changes in insolation were closely related to long-term environmental variations
      in the deep continental interior, over the past 12 million years.

PMID- 11242043
TI  - Earthquake slip on oceanic transform faults.
AB  - Oceanic transform faults are one of the main types of plate boundary, but the
      manner in which they slip remains poorly understood. Early studies suggested that
      relatively slow earthquake rupture might be common; moreover, it has been
      reported that very slow slip precedes some oceanic transform earthquakes,
      including the 1994 Romanche earthquake. The presence of such detectable
      precursors would have obvious implications for earthquake prediction. Here we
      model broadband seismograms of body waves to obtain well-resolved depths and
      rupture mechanisms for 14 earthquakes on the Romanche and Chain transform faults
      in the equatorial Atlantic Ocean. We found that earthquakes on the longer
      Romanche transform are systematically deeper than those on the neighbouring Chain
      transform. These depths indicate that the maximum depth of brittle failure is at
      a temperature of approximately 600 degrees C in oceanic lithosphere. We find that
      the body waves from the Romanche 1994 earthquake can be well modelled with
      relatively deep slip on a single fault, and we use the mechanism and depth of
      this earthquake to recalculate its source spectrum. The previously reported slow
      precursor can be explained as an artefact of uncertainties in the assumed model
      parameters.

PMID- 11242044
TI  - Isotopic evidence for microbial sulphate reduction in the early Archaean era.
AB  - Sulphate-reducing microbes affect the modern sulphur cycle, and may be quite
      ancient, though when they evolved is uncertain. These organisms produce sulphide
      while oxidizing organic matter or hydrogen with sulphate. At sulphate
      concentrations greater than 1 mM, the sulphides are isotopically fractionated
      (depleted in 34S) by 10-40/1000 compared to the sulphate, with fractionations
      decreasing to near 0/1000 at lower concentrations. The isotope record of
      sedimentary sulphides shows large fractionations relative to seawater sulphate by
      2.7 Gyr ago, indicating microbial sulphate reduction. In older rocks, however,
      much smaller fractionations are of equivocal origin, possibly biogenic but also
      possibly volcanogenic. Here we report microscopic sulphides in approximately 3.47
      Gyr-old barites from North Pole, Australia, with maximum fractionations of
      21.1/1000, about a mean of 11.6/1000, clearly indicating microbial sulphate
      reduction. Our results extend the geological record of microbial sulphate
      reduction back more than 750 million years, and represent direct evidence of an
      early specific metabolic pathway--allowing time calibration of a deep node on the
      tree of life.

PMID- 11242045
TI  - A primitive sarcopterygian fish with an eyestalk.
AB  - The discovery of two Early Devonian osteichthyan (bony fish) fossils has
      challenged established ideas about the origin of osteichthyans and their
      divergence into actinopterygians (teleosts and their relatives) and
      sarcopterygians (tetrapods, coelacanths, lungfishes and related groups).
      Psarolepis from China and an unnamed braincase from Australia combine derived
      sarcopterygian and actinopterygian characters with primitive features previously
      restricted to non-osteichthyans, suggesting that early osteichthyan evolution may
      have involved substantial parallellism between sarcopterygians and
      actinopterygians. But interpretation of these fossils has been hampered by poor
      phylogenetic resolution. Here we describe a basal sarcopterygian fish, Achoania
      gen, et sp. nov., that fills the morphological gap between Psarolepis and higher
      sarcoptergyians. We also report the presence of eyestalk attachments in both
      Achoania and Psarolepis, showing that this supposedly non-osteichthyan feature
      occurs in basal sarcopterygians as well as the actinoptergyian-like Australian
      braincase.

PMID- 11242046
TI  - Modulation of the neuronal glutamate transporter EAAC1 by the interacting protein
      GTRAP3-18.
AB  - Excitatory amino-acid carrier 1 (EAAC1) is a high-affinity Na+-dependent L
      glutamate/D,L-aspartate cell-membrane transport protein. It is expressed in brain
      as well as several non-nervous tissues. In brain, EAAC1 is the primary neuronal
      glutamate transporter. It has a polarized distribution in cells and mainly
      functions perisynaptically to transport glutamate from the extracellular
      environment. In the kidney it is involved in renal acidic amino-acid re
      absorption and amino-acid metabolism. Here we describe the identification and
      characterization of an EAAC1-associated protein, GTRAP3-18. Like EAAC1, GTRAP3-18
      is expressed in numerous tissues. It localizes to the cell membrane and
      cytoplasm, and specifically interacts with carboxy-terminal intracellular domain
      of EAAC1. Increasing the expression of GTRAP3-18 in cells reduces EAAC1-mediated
      glutamate transport by lowering substrate affinity. The expression of GTRAP3-18
      can be upregulated by retinoic acid, which results in a specific reduction of
      EAAC1-mediated glutamate transport. These studies show that glutamate transport
      proteins can be regulated potently and that GTRAP can modulate the transport
      functions ascribed to EAAC1. GTRAP3-18 may be important in regulating the
      metabolic function of EAAC1.

PMID- 11242047
TI  - Modulation of the neuronal glutamate transporter EAAT4 by two interacting
      proteins.
AB  - Glutamate is the main excitatory neurotransmitter in the mammalian central
      nervous system and is removed from the synaptic cleft by sodium-dependent
      glutamate transporters. To date, five distinct glutamate transporters have been
      cloned from animal and human tissue: GLAST (EAAT1), GLT-1 (EAAT2), EAAC1 (EAAT3),
      EAAT4, and EAAT5 (refs 1-5). GLAST and GLT-1 are localized primarily in
      astrocytes, whereas EAAC1 (refs 8, 9), EAAT4 (refs 9-11) and EAAT5 (ref 5) are
      neuronal. Studies of EAAT4 and EAAC1 indicate an extrasynaptic localization on
      perisynaptic membranes that are near release sites. This localization facilitates
      rapid glutamate binding, and may have a role in shaping the amplitude of
      postsynaptic responses in densely packed cerebellar terminals. We have used a
      yeast two-hybrid screen to identify interacting proteins that may be involved in
      regulating EAAT4--the glutamate transporter expressed predominately in the
      cerebellum--or in targeting and/or anchoring or clustering the transporter to the
      target site. Here we report the identification and characterization of two
      proteins, GTRAP41 and GTRAP48 (for glutamate transporter EAAT4 associated
      protein) that specifically interact with the intracellular carboxy-terminal
      domain of EAAT4 and modulate its glutamate transport activity.

PMID- 11242048
TI  - Aberrant CFTR-dependent HCO3- transport in mutations associated with cystic
      fibrosis.
AB  - Cystic fibrosis (CF) is a disease caused by mutations in the cystic fibrosis
      transmembrane conductance regulator (CFTR). Initially, Cl- conductance in the
      sweat duct was discovered to be impaired in CF, a finding that has been extended
      to all CFTR-expressing cells. Subsequent cloning of the gene showed that CFTR
      functions as a cyclic-AMP-regulated Cl- channel; and some CF-causing mutations
      inhibit CFTR Cl- channel activity. The identification of additional CF-causing
      mutants with normal Cl- channel activity indicates, however, that other CFTR
      dependent processes contribute to the disease. Indeed, CFTR regulates other
      transporters, including Cl(-)-coupled HCO3- transport. Alkaline fluids are
      secreted by normal tissues, whereas acidic fluids are secreted by mutant CFTR
      expressing tissues, indicating the importance of this activity. HCO3- and pH
      affect mucin viscosity and bacterial binding. We have examined Cl(-)-coupled HCO3
      transport by CFTR mutants that retain substantial or normal Cl- channel
      activity. Here we show that mutants reported to be associated with CF with
      pancreatic insufficiency do not support HCO3- transport, and those associated
      with pancreatic sufficiency show reduced HCO3- transport. Our findings
      demonstrate the importance of HCO3- transport in the function of secretory
      epithelia and in CF.

PMID- 11242049
TI  - Tbx1 haploinsufficieny in the DiGeorge syndrome region causes aortic arch defects
      in mice.
AB  - DiGeorge syndrome is characterized by cardiovascular, thymus and parathyroid
      defects and craniofacial anomalies, and is usually caused by a heterozygous
      deletion of chromosomal region 22q11.2 (del22q11) (ref. 1). A targeted,
      heterozygous deletion, named Df(16)1, encompassing around 1 megabase of the
      homologous region in mouse causes cardiovascular abnormalities characteristic of
      the human disease. Here we have used a combination of chromosome engineering and
      P1 artificial chromosome transgenesis to localize the haploinsufficient gene in
      the region, Tbx1. We show that Tbx1, a member of the T-box transcription factor
      family, is required for normal development of the pharyngeal arch arteries in a
      gene dosage-dependent manner. Deletion of one copy of Tbx1 affects the
      development of the fourth pharyngeal arch arteries, whereas homozygous mutation
      severely disrupts the pharyngeal arch artery system. Our data show that
      haploinsufficiency of Tbx1 is sufficient to generate at least one important
      component of the DiGeorge syndrome phenotype in mice, and demonstrate the
      suitability of the mouse for the genetic dissection of microdeletion syndromes.

PMID- 11242050
TI  - Visualizing the generation of memory CD4 T cells in the whole body.
AB  - It is thought that immunity depends on naive CD4 T cells that proliferate in
      response to microbial antigens, differentiate into memory cells that produce anti
      microbial lymphokines, and migrate to sites of infection. Here we use
      immunohistology to enumerate individual naive CD4 T cells, specific for a model
      antigen, in the whole bodies of adult mice. The cells resided exclusively in
      secondary lymphoid tissues, such as the spleen and lymph nodes, in mice that were
      not exposed to antigen. After injection of antigen alone into the blood, the T
      cells proliferated, migrated to the lungs, liver, gut and salivary glands, and
      then disappeared from these organs. If antigen was injected with the microbial
      product lipopolysaccharide, proliferation and migration were enhanced, and two
      populations of memory cells survived for months: one in the lymph nodes that
      produced the growth factor interleukin-2, and a larger one in the non-lymphoid
      tissues that produced the anti-microbial lymphokine interferon-gamma. These
      results show that antigen recognition in the context of infection generates
      memory cells that are specialized to proliferate in the secondary lymphoid
      tissues or to fight infection at the site of microbial entry.

PMID- 11242051
TI  - Skewed maturation of memory HIV-specific CD8 T lymphocytes.
AB  - Understanding the lineage differentiation of memory T cells is a central question
      in immunology. We investigated this issue by analysing the expression of the
      chemokine receptor CCR7, which defines distinct subsets of naive and memory T
      lymphocytes with different homing and effector capacities and antiviral immune
      responses to HIV and cytomegalovirus. Ex vivo analysis of the expression of
      CD45RA and CCR7 antigens, together with in vitro analysis of the cell-division
      capacity of different memory CD8+ T-cell populations, identified four subsets of
      HIV- and CMV-specific CD8+ T lymphocytes, and indicated the following lineage
      differentiation pattern: CD45RA+ CCR7+ --> CD45RA- CCR7+ --> CD45RA- CCR7- -->
      CD45RA+ CCR7-. Here we demonstrate through analysis of cell division
      (predominantly restricted to the CCR7+ CD8+ T-cell subsets) that the
      differentiation of antigen-specific CD8+ T cells is a two-step process
      characterized initially by a phase of proliferation largely restricted to the
      CCR7+ CD8+ cell subsets, followed by a phase of functional maturation
      encompassing the CCR7- CD8+ cell subsets. The distribution of these populations
      in HIV- and CMV-specific CD8+ T cells showed that the HIV-specific cell pool was
      predominantly (70%) composed of pre-terminally differentiated CD45RA- CCR7-
      cells, whereas the CMV-specific cell pool consisted mainly (50%) of the
      terminally differentiated CD45RA+ CCR7- cells. These results demonstrate a skewed
      maturation of HIV-specific memory CD8+ T cells during HIV infection.

PMID- 11242052
TI  - A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase
      activity and apoptosis.
AB  - X-linked inhibitor-of-apoptosis protein (XIAP) interacts with caspase-9 and
      inhibits its activity, whereas Smac (also known as DIABLO) relieves this
      inhibition through interaction with XIAP. Here we show that XIAP associates with
      the active caspase-9-Apaf-1 holoenzyme complex through binding to the amino
      terminus of the linker peptide on the small subunit of caspase-9, which becomes
      exposed after proteolytic processing of procaspase-9 at Asp315. Supporting this
      observation, point mutations that abrogate the proteolytic processing but not the
      catalytic activity of caspase-9, or deletion of the linker peptide, prevented
      caspase-9 association with XIAP and its concomitant inhibition. We note that the
      N-terminal four residues of caspase-9 linker peptide share significant homology
      with the N-terminal tetra-peptide in mature Smac and in the Drosophila proteins
      Hid/Grim/Reaper, defining a conserved class of IAP-binding motifs. Consistent
      with this finding, binding of the caspase-9 linker peptide and Smac to the BIR3
      domain of XIAP is mutually exclusive, suggesting that Smac potentiates caspase-9
      activity by disrupting the interaction of the linker peptide of caspase-9 with
      BIR3. Our studies reveal a mechanism in which binding to the BIR3 domain by two
      conserved peptides, one from Smac and the other one from caspase-9, has opposing
      effects on caspase activity and apoptosis.

PMID- 11242053
TI  - Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins.
AB  - Distinct modifications of histone amino termini, such as acetylation,
      phosphorylation and methylation, have been proposed to underlie a chromatin-based
      regulatory mechanism that modulates the accessibility of genetic information. In
      addition to histone modifications that facilitate gene activity, it is of similar
      importance to restrict inappropriate gene expression if cellular and
      developmental programmes are to proceed unperturbed. Here we show that mammalian
      methyltransferases that selectively methylate histone H3 on lysine 9 (Suv39h
      HMTases) generate a binding site for HP1 proteins--a family of heterochromatic
      adaptor molecules implicated in both gene silencing and supra-nucleosomal
      chromatin structure. High-affinity in vitro recognition of a methylated histone
      H3 peptide by HP1 requires a functional chromo domain; thus, the HP1 chromo
      domain is a specific interaction motif for the methyl epitope on lysine9 of
      histone H3. In vivo, heterochromatin association of HP1 proteins is lost in
      Suv39h double-null primary mouse fibroblasts but is restored after the re
      introduction of a catalytically active SWUV39H1 HMTase. Our data define a
      molecular mechanism through which the SUV39H-HP1 methylation system can
      contribute to the propagation of heterochromatic subdomains in native chromatin.

PMID- 11242055
TI  - Scanning the spectrum.

PMID- 11242054
TI  - Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo
      domain.
AB  - Heterochromatin protein 1 (HP1) is localized at heterochromatin sites where it
      mediates gene silencing. The chromo domain of HP1 is necessary for both targeting
      and transcriptional repression. In the fission yeast Schizosaccharomyces pombe,
      the correct localization of Swi6 (the HP1 equivalent) depends on Clr4, a
      homologue of the mammalian SUV39H1 histone methylase. Both Clr4 and SUV39H1
      methylate specifically lysine 9 of histone H3 (ref. 6). Here we show that HP1 can
      bind with high affinity to histone H3 methylated at lysine 9 but not at lysine 4.
      The chromo domain of HP1 is identified as its methyl-lysine-binding domain. A
      point mutation in the chromo domain, which destroys the gene silencing activity
      of HP1 in Drosophila, abolishes methyl-lysine-binding activity. Genetic and
      biochemical analysis in S. pombe shows that the methylase activity of Clr4 is
      necessary for the correct localization of Swi6 at centromeric heterochromatin and
      for gene silencing. These results provide a stepwise model for the formation of a
      transcriptionally silent heterochromatin: SUV39H1 places a 'methyl marker' on
      histone H3, which is then recognized by HP1 through its chromo domain. This model
      may also explain the stable inheritance of the heterochromatic state.

PMID- 11242057
TI  - Sandia scientists develop instruments at the crossroads.

PMID- 11242056
TI  - Better microscopes will be instrumental in nanotechnology development.

PMID- 11242058
TI  - Mass-spectrometry experience is in demand.

PMID- 11242064
TI  - Amyloid fibrils from muscle myoglobin.

PMID- 11242065
TI  - Pattern formation. Spiral cracks without twisting.

PMID- 11242068
TI  - Nanotechnology. Thin solid films roll up into nanotubes.

PMID- 11242066
TI  - Polynesian origins. Slow boat to Melanesia?

PMID- 11242069
TI  - A measurement of the cosmological mass density from clustering in the 2dF Galaxy
      Redshift Survey.
AB  - The large-scale structure in the distribution of galaxies is thought to arise
      from the gravitational instability of small fluctuations in the initial density
      field of the Universe. A key test of this hypothesis is that forming
      superclusters of galaxies should generate a systematic infall of other galaxies.
      This would be evident in the pattern of recessional velocities, causing an
      anisotropy in the inferred spatial clustering of galaxies. Here we report a
      precise measurement of this clustering, using the redshifts of more than 141,000
      galaxies from the two-degree-field (2dF) galaxy redshift survey. We determine the
      parameter beta = Omega0.6/b = 0.43 +/- 0.07, where Omega is the total mass
      density parameter of the Universe and b is a measure of the 'bias' of the
      luminous galaxies in the survey. (Bias is the difference between the clustering
      of visible galaxies and of the total mass, most of which is dark.) Combined with
      the anisotropy of the cosmic microwave background, our results favour a low
      density Universe with Omega approximately 0.3.

PMID- 11242071
TI  - Observation of orbital waves as elementary excitations in a solid.
AB  - A basic concept in solid-state physics is that when some kind of symmetry in a
      solid is spontaneously broken, collective excitations will arise. For example,
      phonons are the collective excitations corresponding to lattice vibrations in a
      crystal, and magnons correspond to spin waves in a magnetically ordered compound.
      Modulations in the relative shape of the electronic clouds in an orbitally
      ordered state could in principle give rise to orbital waves, or 'orbitons', but
      this type of elementary excitation has yet to be observed experimentally. Systems
      in which the electrons are strongly correlated-such as high-temperature
      superconductors and manganites exhibiting colossal magnetoresistivity-are
      promising candidates for supporting orbital waves, because they contain
      transition-metal ions in which the orbital degree of freedom is important.
      Orbitally ordered states have been found in several transition-metal compounds,
      and orbitons have been predicted theoretically for LaMnO3. Here we report
      experimental evidence for orbitons in LaMnO3, using Raman scattering
      measurements. We perform a model calculation of orbiton resonances which provides
      a good fit to the experimental data.

PMID- 11242070
TI  - Defining brain wiring patterns and mechanisms through gene trapping in mice.
AB  - The search to understand the mechanisms regulating brain wiring has relied on
      biochemical purification approaches in vertebrates and genetic approaches in
      invertebrates to identify molecular cues and receptors for axon guidance. Here we
      describe a phenotype-based gene-trap screen in mice designed for the large-scale
      identification of genes controlling the formation of the trillions of connections
      in the mammalian brain. The method incorporates an axonal marker, which helps to
      identify cell-autonomous mechanisms in axon guidance, and has generated a
      resource of mouse lines with striking patterns of axonal labelling, which
      facilitates analysis of the normal wiring diagram of the brain. Studies of two of
      these mouse lines have identified an in vivo guidance function for a vertebrate
      transmembrane semaphorin, Sema6A, and have helped re-evaluate that of the Eph
      receptor EphA4.

PMID- 11242072
TI  - Coherent branched flow in a two-dimensional electron gas.
AB  - Semiconductor nanostructures based on two-dimensional electron gases (2DEGs)
      could form the basis of future devices for sensing, information processing and
      quantum computation. Although electron transport in 2DEG nanostructures has been
      well studied, and many remarkable phenomena have already been discovered (for
      example, weak localization, quantum chaos, universal conductance fluctuations),
      fundamental aspects of the electron flow through these structures have so far not
      been clarified. However, it has recently become possible to image current
      directly through 2DEG devices using scanning probe microscope techniques. Here,
      we use such a technique to observe electron flow through a narrow constriction in
      a 2DEG-a quantum point contact. The images show that the electron flow from the
      point contact forms narrow, branching strands instead of smoothly spreading fans.
      Our theoretical study of this flow indicates that this branching of current flux
      is due to focusing of the electron paths by ripples in the background potential.
      The strands are decorated by interference fringes separated by half the Fermi
      wavelength, indicating the persistence of quantum mechanical phase coherence in
      the electron flow. These findings may have important implications for a better
      understanding of electron transport in 2DEGs and for the design of future
      nanostructure devices.

PMID- 11242073
TI  - Strongly linked current flow in polycrystalline forms of the superconductor MgB2.
AB  - The discovery of superconductivity at 39 K in magnesium diboride, MgB2, raises
      many issues, a critical one being whether this material resembles a high
      temperature copper oxide superconductor or a low-temperature metallic
      superconductor in terms of its behaviour in strong magnetic fields. Although the
      copper oxides exhibit very high transition temperatures, their in-field
      performance is compromized by their large anisotropy, the result of which is to
      restrict high bulk current densities to a region much less than the full magnetic
      field-temperature (H-T) space over which superconductivity is found. Moreover,
      the weak coupling across grain boundaries makes transport current densities in
      untextured polycrystalline samples low and strongly sensitive to magnetic field.
      Here we report that, despite the multiphase, untextured, microscale, subdivided
      nature of our MgB2 samples, supercurrents flow throughout the material without
      exhibiting strong sensitivity to weak magnetic fields. Our combined
      magnetization, magneto-optical, microscopy and X-ray investigations show that the
      supercurrent density is mostly determined by flux pinning, rather than by the
      grain boundary connectivity. Our results therefore suggest that this new
      superconductor class is not compromized by weak-link problems, a conclusion of
      significance for practical applications if higher temperature analogues of this
      compound can be discovered.

PMID- 11242074
TI  - Gate-induced superconductivity in a solution-processed organic polymer film.
AB  - The electrical and optical properties of conjugated polymers have received
      considerable attention in the context of potentially low-cost replacements for
      conventional metals and inorganic semiconductors. Charge transport in these
      organic materials has been characterized in both the doped-metallic and the
      semiconducting state, but superconductivity has not hitherto been observed in
      these polymers. Here we report a distinct metal-insulator transition and metallic
      levels of conductivity in a polymer field-effect transistor. The active material
      is solution-cast regioregular poly(3-hexylthiophene), which forms relatively well
      ordered films owing to self-organization, and which yields a high charge carrier
      mobility (0.05-0.1 cm2 V(-1) s(-1)) at room temperature. At temperatures below
      approximately 2.35 K with sheet carrier densities exceeding 2.5 x 10(14) cm(-2),
      the polythiophene film becomes superconducting. The appearance of
      superconductivity seems to be closely related to the self-assembly properties of
      the polymer, as the introduction of additional disorder is found to suppress
      superconductivity. Our findings therefore demonstrate the feasibility of tuning
      the electrical properties of conjugated polymers over the largest range possible
      from insulating to superconducting.

PMID- 11242075
TI  - An efficient room-temperature silicon-based light-emitting diode.
AB  - There is an urgent requirement for an optical emitter that is compatible with
      standard, silicon-based ultra-large-scale integration (ULSI) technology. Bulk
      silicon has an indirect energy bandgap and is therefore highly inefficient as a
      light source, necessitating the use of other materials for the optical emitters.
      However, the introduction of these materials is usually incompatible with the
      strict processing requirements of existing ULSI technologies. Moreover, as the
      length scale of the devices decreases, electrons will spend increasingly more of
      their time in the connections between components; this interconnectivity problem
      could restrict further increases in computer chip processing power and speed in
      as little as five years. Many efforts have therefore been directed, with varying
      degrees of success, to engineering silicon-based materials that are efficient
      light emitters. Here, we describe the fabrication, using standard silicon
      processing techniques, of a silicon light-emitting diode (LED) that operates
      efficiently at room temperature. Boron is implanted into silicon both as a dopant
      to form a p-n junction, as well as a means of introducing dislocation loops. The
      dislocation loops introduce a local strain field, which modifies the band
      structure and provides spatial confinement of the charge carriers. It is this
      spatial confinement which allows room-temperature electroluminescence at the band
      edge. This device strategy is highly compatible with ULSI technology, as boron
      ion implantation is already used as a standard method for the fabrication of
      silicon devices.

PMID- 11242076
TI  - Dating of the oldest continental sediments from the Himalayan foreland basin.
AB  - A detailed knowledge of Himalayan development is important for our wider
      understanding of several global processes, ranging from models of plateau uplift
      to changes in oceanic chemistry and climate. Continental sediments 55 Myr old
      found in a foreland basin in Pakistan are, by more than 20 Myr, the oldest
      deposits thought to have been eroded from the Himalayan metamorphic mountain
      belt. This constraint on when erosion began has influenced models of the timing
      and diachrony of the India-Eurasia collision, timing and mechanisms of exhumation
      and uplift, as well as our general understanding of foreland basin dynamics. But
      the depositional age of these basin sediments was based on biostratigraphy from
      four intercalated marl units. Here we present dates of 257 detrital grains of
      white mica from this succession, using the 40Ar-39Ar method, and find that the
      largest concentration of ages are at 36-40 Myr. These dates are incompatible with
      the biostratigraphy unless the mineral ages have been reset, a possibility that
      we reject on the basis of a number of lines of evidence. A more detailed mapping
      of this formation suggests that the marl units are structurally intercalated with
      the continental sediments and accordingly that biostratigraphy cannot be used to
      date the clastic succession. The oldest continental foreland basin sediments
      containing metamorphic detritus eroded from the Himalaya orogeny therefore seem
      to be at least 15-20 Myr younger than previously believed, and models based on
      the older age must be re-evaluated.

PMID- 11242077
TI  - Evidence for mantle metasomatism by hydrous silicic melts derived from subducted
      oceanic crust.
AB  - The low concentrations of niobium, tantalum and titanium observed in island-arc
      basalts are thought to result from modification of the sub-arc mantle by a
      metasomatic agent, deficient in these elements, that originates from within the
      subducted oceanic crust. Whether this agent is an hydrous fluid or a silica-rich
      melt has been discussed using mainly a trace-element approach and related to
      variable thermal regimes of subduction zones. Melting of basalt in the absence of
      fluid both requires high temperatures and yields melt compositions unlike those
      found in most modern or Mesozoic island arcs. Thus, metasomatism by fluids has
      been thought to be the most common situation. Here, however, we show that the
      melting of basalt under both H2O-added and low-temperature conditions can yield
      extremely alkali-rich silicic liquids, the alkali content of which increases with
      pressure. These liquids are deficient in titanium and in the elements niobium and
      tantalum and are virtually identical to glasses preserved in mantle xenoliths
      found in subduction zones and to veins found in exhumed metamorphic terranes of
      fossil convergent zones. We also found that the interaction between such liquids
      and mantle olivine produces modal mineralogies that are identical to those
      observed in metasomatized Alpine-type peridotites. We therefore suggest that
      mantle metasomatism by slab-derived melt is a more common process than previously
      thought.

PMID- 11242078
TI  - Branched integumental structures in Sinornithosaurus and the origin of feathers.
AB  - The evolutionary origin of feathers has long been obscured because no
      morphological antecedents were known to the earliest, structurally modern
      feathers of Archaeopteryx. It has been proposed that the filamentous integumental
      appendages on several theropod dinosaurs are primitive feathers; but the homology
      between these filamentous structures and feathers has been disputed, and two taxa
      with true feathers (Caudipteryx and Protarchaeopteryx) have been proposed to be
      flightless birds. Confirmation of the theropod origin of feathers requires
      documentation of unambiguously feather-like structures in a clearly non-avian
      theropod. Here we describe our observations of the filamentous integumental
      appendages of the basal dromaeosaurid dinosaur Sinornithosaurus millenii, which
      indicate that they are compound structures composed of multiple filaments.
      Furthermore, these appendages exhibit two types of branching structure that are
      unique to avian feathers: filaments joined in a basal tuft, and filaments joined
      at their bases in series along a central filament. Combined with the independent
      phylogenetic evidence supporting the theropod ancestry of birds, these
      observations strongly corroborate the hypothesis that the integumental appendages
      of Sinornithosaurus are homologous with avian feathers. The plesiomorphic
      feathers of Sinornithosaurus also conform to the predictions of an independent,
      developmental model of the evolutionary origin of feathers.

PMID- 11242079
TI  - Sexual swellings advertise female quality in wild baboons.
AB  - The females of many Old World primate species produce prominent and conspicuous
      swellings of the perineal skin around the time of ovulation. These sexual
      swellings have been proposed to increase competition among males for females or
      to increase the likelihood of a female getting fertilized, by signalling either a
      female's general reproductive status, or the timing of her ovulation. Here we
      show that sexual swellings in wild baboons reliably advertise a female's
      reproductive value over her lifetime, in accordance with a theoretical model of
      honest signalling. Females with larger swellings attained sexual maturity
      earlier, produced both more offspring and more surviving offspring per year than
      females with smaller swellings, and had a higher overall proportion of their
      offspring survive. Male baboons use the size of the sexual swelling to determine
      their mating effort, fighting more aggressively to consort females with larger
      swellings, and spending more time grooming these females. Our results document an
      unusual case of a sexually selected ornament in females, and show how males, by
      mating selectively on the basis of the size of the sexual swelling, increase
      their probability of mating with females more likely to produce surviving
      offspring.

PMID- 11242080
TI  - Mice lacking the M3 muscarinic acetylcholine receptor are hypophagic and lean.
AB  - Members of the muscarinic acetylcholine receptor family (M1-M5) have central
      roles in the regulation of many fundamental physiological functions. Identifying
      the specific receptor subtype(s) that mediate the diverse muscarinic actions of
      acetylcholine is of considerable therapeutic interest, but has proved difficult
      primarily because of a lack of subtype-selective ligands. Here we show that mice
      deficient in the M3 muscarinic receptor (M3R-/- mice) display a significant
      decrease in food intake, reduced body weight and peripheral fat deposits, and
      very low levels of serum leptin and insulin. Paradoxically, hypothalamic
      messenger RNA levels of melanin-concentrating hormone (MCH), which are normally
      upregulated in fasted animals leading to an increase in food intake, are
      significantly reduced in M3R-/- mice. Intra-cerebroventricular injection studies
      show that an agouti-related peptide analogue lacked orexigenic (appetite
      stimulating) activity in M3R-/- mice. However, M3R-/- mice remained responsive to
      the orexigenic effects of MCH. Our data indicate that there may be a cholinergic
      pathway that involves M3-receptor-mediated facilitation of food intake at a site
      downstream of the hypothalamic leptin/melanocortin system and upstream of the MCH
      system.

PMID- 11242081
TI  - NO-independent regulatory site on soluble guanylate cyclase.
AB  - Nitric oxide (NO) is a widespread, potent, biological mediator that has many
      physiological and pathophysiological roles. Research in the field of NO appears
      to have followed a straightforward path, and the findings have been progressive:
      NO and cyclic GMP are involved in vasodilatation; glycerol trinitrate relaxes
      vascular smooth muscles by bioconversion to NO; mammalian cells synthesize NO;
      and last, NO mediates vasodilatation by stimulating the soluble guanylate cyclase
      (sGC), a heterodimeric (alpha/beta) haem protein that converts GTP to cGMP2-4.
      Here we report the discovery of a regulatory site on sGC. Using photoaffinity
      labelling, we have identified the cysteine 238 and cysteine 243 region in the
      alpha1-subunit of sGC as the target for a new type of sGC stimulator. Moreover,
      we present a pyrazolopyridine, BAY 41-2272, that potently stimulates sGC through
      this site by a mechanism that is independent of NO. This results in antiplatelet
      activity, a strong decrease in blood pressure and an increase in survival in a
      low-NO rat model of hypertension, and as such may offer an approach for treating
      cardiovascular diseases.

PMID- 11242082
TI  - Polo-like kinase 1 phosphorylates cyclin B1 and targets it to the nucleus during
      prophase.
AB  - In vertebrate cells, the nuclear entry of Cdc2-cyclin B1 (MPF) during prophase is
      thought to be essential for the induction and coordination of M-phase events.
      Phosphorylation of cyclin B1 is central to its nuclear translocation, but the
      kinases that are responsible remain unknown. Here we have purified a protein
      kinase from Xenopus M-phase extracts that phosphorylates a crucial serine residue
      (S147) in the middle of the nuclear export signal sequence of cyclin B1. We have
      identified this kinase as Plx1 (ref. 16), a Xenopus homologue of Polo-like kinase
      (Plk)-1. During cell-cycle progression in HeLa cells, a change in the kinase
      activity of endogenous Plk1 toward S147 and/or S133 correlates with a kinase
      activity in the cell extracts. An anti-Plk1 antibody depletes the M-phase
      extracts of the kinase activity toward S147 and/or S133. An anti-phospho-S147
      antibody reacts specifically with cyclin B1 only during G2/M phase. A mutant
      cyclin B1 in which S133 and S147 are replaced by alanines remains in the
      cytoplasm, whereas wild-type cyclin B1 accumulates in the nucleus during
      prophase. Co-expression of constitutively active Plk1 stimulates nuclear entry of
      cyclin B1. Our results indicate that Plk1 may be involved in targeting MPF to the
      nucleus during prophase.

PMID- 11242083
TI  - The S-locus receptor kinase is inhibited by thioredoxins and activated by pollen
      coat proteins.
AB  - The self-incompatibility response in Brassica allows recognition and rejection of
      self-pollen by the stigmatic papillae. The transmembrane S-locus receptor kinase
      (SRK), a member of the receptor-like kinase superfamily in plants, mediates
      recognition of self-pollen on the female side, whereas the S-locus cysteine-rich
      protein (SCR) is the male component of the self-incompatibility response. SCR is
      presumably located in the pollen coat, and is thought to be the SRK ligand.
      Although many receptor-like kinases have been isolated in plants, the mechanisms
      of signal transduction mediated by these molecules remain largely unknown. Here
      we show that SRK is phosphorylated in vivo within one hour of self-pollination.
      We also show that, in vitro, autophosphorylation of SRK is prevented by the
      stigma thioredoxin THL1 in the absence of a ligand. This inhibition is released
      in a haplotype-specific manner by the addition of pollen coat proteins. Our data
      indicate that SRK is inhibited by thioredoxins and activated by pollen coat
      proteins.

PMID- 11242084
TI  - Conformational diversity in a yeast prion dictates its seeding specificity.
AB  - A perplexing feature of prion-based inheritance is that prions composed of the
      same polypeptide can evoke different phenotypes (such as distribution of brain
      lesions), even when propagated in genetically identical hosts. The molecular
      basis of this strain diversity and the relationship between strains and barriers
      limiting transmission between species remain unclear. We have used the yeast
      prion phenomenon [PSI+]4 to investigate these issues and examine the role that
      conformational differences may have in prion strains. We have made a chimaeric
      fusion between the prion domains of two species (Saccharomyces cerevisae and
      Candida albicans) of Sup35, the protein responsible for [PSI+]. Here we report
      that this chimaera forms alternate prion strains in vivo when initiated by
      transient overexpression of different Sup35 species. Similarly, in vitro the
      purified chimaera, when seeded with different species of Sup35 fibres,
      establishes and propagates distinct amyloid conformations. These fibre
      conformations dictate amyloid seeding specificity: a chimaera seeded by S.
      cerevisiae fibres efficiently catalyses conversion of S. cerevisiae Sup35 but not
      of C. albicans Sup35, and vice versa. These and other considerations argue that
      heritable prion strains result from self-propagating conformational differences
      within the prion protein itself. Moreover, these conformational differences seem
      to act in concert with the primary structure to determine a prion's propensity
      for transmission across a species barrier.

PMID- 11242085
TI  - Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans.
AB  - In Caenorhabditis elegans, mutations that reduce the activity of an insulin-like
      receptor (daf-2) or a phosphatidylinositol-3-OH kinase (age-1) favour entry into
      the dauer state during larval development and extend lifespan in adults.
      Downregulation of this pathway activates a forkhead transcription factor (daf
      16), which may regulate targets that promote dauer formation in larvae and stress
      resistance and longevity in adults. In yeast, the SIR2 gene determines the
      lifespan of mother cells, and adding an extra copy of SIR2 extends lifespan. Sir2
      mediates chromatin silencing through a histone deacetylase activity that depends
      on NAD (nicotinamide adenine dinucleotide) as a cofactor. We have surveyed the
      lifespan of C. elegans strains containing duplications of chromosomal regions.
      Here we report that a duplication containing sir-2.1-the C. elegans gene most
      homologous to yeast SIR2-confers a lifespan that is extended by up to 50%.
      Genetic analysis indicates that the sir-2.1 transgene functions upstream of daf
      16 in the insulin-like signalling pathway. Our findings suggest that Sir2
      proteins may couple longevity to nutrient availability in many eukaryotic
      organisms.

PMID- 11242086
TI  - GTPase activity of dynamin and resulting conformation change are essential for
      endocytosis.
AB  - Dynamin is a large GTPase with a relative molecular mass of 96,000 (Mr 96K) that
      is involved in clathrin-mediated endocytosis and other vesicular trafficking
      processes. Although its function is apparently essential for scission of newly
      formed vesicles from the plasma membrane, the nature of dynamin's role in the
      scission process is still unclear. It has been proposed that dynamin is a
      regulator (similar to classical G proteins) of downstream effectors. Here we
      report the analysis of several point mutants of dynamin's GTPase effector (GED)
      and GTPase domains. We show that oligomerization and GTP binding alone, by
      dynamin, are not sufficient for endocytosis in vivo. Rather, efficient GTP
      hydrolysis and an associated conformational change are also required. These data
      argue that dynamin has a mechanochemical function in vesicle scission.

PMID- 11242087
TI  - A mechanism for initiating RNA-dependent RNA polymerization.
AB  - In most RNA viruses, genome replication and transcription are catalysed by a
      viral RNA-dependent RNA polymerase. Double-stranded RNA viruses perform these
      operations in a capsid (the polymerase complex), using an enzyme that can read
      both single- and double-stranded RNA. Structures have been solved for such viral
      capsids, but they do not resolve the polymerase subunits in any detail. Here we
      show that the 2 A resolution X-ray structure of the active polymerase subunit
      from the double-stranded RNA bacteriophage straight phi6 is highly similar to
      that of the polymerase of hepatitis C virus, providing an evolutionary link
      between double-stranded RNA viruses and flaviviruses. By crystal soaking and co
      crystallization, we determined a number of other structures, including complexes
      with oligonucleotide and/or nucleoside triphosphates (NTPs), that suggest a
      mechanism by which the incoming double-stranded RNA is opened up to feed the
      template through to the active site, while the substrates enter by another route.
      The template strand initially overshoots, locking into a specificity pocket, and
      then, in the presence of cognate NTPs, reverses to form the initiation complex;
      this process engages two NTPs, one of which acts with the carboxy-terminal domain
      of the protein to prime the reaction. Our results provide a working model for the
      initiation of replication and transcription.

PMID- 11242092
TI  - Harvesting the fruits of the human genome.

PMID- 11242093
TI  - The end of all human DNA maps?

PMID- 11242094
TI  - BACking up the promises.

PMID- 11242095
TI  - Chipping away at the transcriptome.

PMID- 11242096
TI  - Variation is the spice of life.

PMID- 11242097
TI  - Gamma-H2AX illuminates meiosis.

PMID- 11242098
TI  - Deconstructing DiGeorge syndrome.

PMID- 11242099
TI  - Chipping away at chromatin.

PMID- 11242102
TI  - DNA double-strand breaks: signaling, repair and the cancer connection.
AB  - To ensure the high-fidelity transmission of genetic information, cells have
      evolved mechanisms to monitor genome integrity. Cells respond to DNA damage by
      activating a complex DNA-damage-response pathway that includes cell-cycle arrest,
      the transcriptional and post-transcriptional activation of a subset of genes
      including those associated with DNA repair, and, under some circumstances, the
      triggering of programmed cell death. An inability to respond properly to, or to
      repair, DNA damage leads to genetic instability, which in turn may enhance the
      rate of cancer development. Indeed, it is becoming increasingly clear that
      deficiencies in DNA-damage signaling and repair pathways are fundamental to the
      etiology of most, if not all, human cancers. Here we describe recent progress in
      our understanding of how cells detect and signal the presence and repair of one
      particularly important form of DNA damage induced by ionizing radiation-the DNA
      double-strand break (DSB). Moreover, we discuss how tumor suppressor proteins
      such as p53, ATM, Brca1 and Brca2 have been linked to such pathways, and how
      accumulating evidence is connecting deficiencies in cellular responses to DNA
      DSBs with tumorigenesis.

PMID- 11242103
TI  - Evolution of imprinting mechanisms: the battle of the sexes begins in the zygote.

PMID- 11242104
TI  - Selection for transgene homozygosity in embryonic stem cells results in extensive
      loss of heterozygosity.
AB  - Embryonic stem cells offer unprecedented opportunities for random or targeted
      genome alterations in the mouse. We present here an efficient strategy to create
      chromosome-specific loss of heterozygosity in embryonic stem cells. The
      combination of this method with genome-wide mutagenesis in ES cells (using
      chemical mutagens or gene-trap vectors) opens up the possibility for in vitro or
      in vivo functional screening of recessive mutations in the mouse.

PMID- 11242105
TI  - Multigenic control of Listeria monocytogenes susceptibility in mice.
AB  - We have used a novel quantitative trait locus model to study the genetics of
      survival of F2 progeny of susceptible BALB/cByJ and resistant C57BL/6ByJ mice
      that have been infected with Listeria monocytogenes. This allowed us to map
      modifiers of L. monocytogenes susceptibility to chromosomes 5 and 13.

PMID- 11242106
TI  - SPTLC1 is mutated in hereditary sensory neuropathy, type 1.
AB  - Hereditary sensory neuropathy type 1 (HSN1, MIM 162400; ref. 1) genetically maps
      to human chromosome 9q22 (refs. 2-4). We report here that the gene encoding a
      subunit of serine palmitoyltransferase is located within the HSN1 locus,
      expressed in dorsal root ganglia (DRG) and mutated in HSN1.

PMID- 11242107
TI  - Dominant-negative mutations of CEBPA, encoding CCAAT/enhancer binding protein
      alpha (C/EBPalpha), in acute myeloid leukemia.
AB  - The transcription factor C/EBPalpha (for CCAAT/enhancer binding protein-alpha;
      encoded by the gene CEBPA) is crucial for the differentiation of granulocytes.
      Conditional expression of C/EBPalpha triggers neutrophilic differentiation, and
      no mature granulocytes are observed in Cebpa-mutant mice. Here we identify
      heterozygous mutations in CEBPA in ten patients with acute myeloid leukemia
      (AML). We found that five mutations in the amino terminus truncate the full
      length protein, but did not affect a 30-kD protein initiated further downstream.
      The mutant proteins block wild-type C/EBPalpha DNA binding and transactivation of
      granulocyte target genes in a dominant-negative manner, and fails to induce
      granulocytic differentiation. Ours is the first report of CEBPA mutations in
      human neoplasia, and such mutations are likely to induce the differentiation
      block found in AML.

PMID- 11242108
TI  - Recombinational DNA double-strand breaks in mice precede synapsis.
AB  - In Saccharomyces cerevisiae, meiotic recombination is initiated by Spo11
      dependent double-strand breaks (DSBs), a process that precedes homologous
      synapsis. Here we use an antibody specific for a phosphorylated histone (gamma
      H2AX, which marks the sites of DSBs) to investigate the timing, distribution and
      Spo11-dependence of meiotic DSBs in the mouse. We show that, as in yeast,
      recombination in the mouse is initiated by Spo11-dependent DSBs that form during
      leptotene. Loss of gamma-H2AX staining (which in irradiated somatic cells is
      temporally linked with DSB repair) is temporally and spatially correlated with
      synapsis, even when this synapsis is 'non-homologous'.

PMID- 11242109
TI  - X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by
      impaired NF-kappaB signaling.
AB  - The molecular basis of X-linked recessive anhidrotic ectodermal dysplasia with
      immunodeficiency (EDA-ID) has remained elusive. Here we report hypomorphic
      mutations in the gene IKBKG in 12 males with EDA-ID from 8 kindreds, and 2
      patients with a related and hitherto unrecognized syndrome of EDA-ID with
      osteopetrosis and lymphoedema (OL-EDA-ID). Mutations in the coding region of
      IKBKG are associated with EDA-ID, and stop codon mutations, with OL-EDA-ID. IKBKG
      encodes NEMO, the regulatory subunit of the IKK (IkappaB kinase) complex, which
      is essential for NF-kappaB signaling. Germline loss-of-function mutations in
      IKBKG are lethal in male fetuses. We show that IKBKG mutations causing OL-EDA-ID
      and EDA-ID impair but do not abolish NF-kappaB signaling. We also show that the
      ectodysplasin receptor, DL, triggers NF-kappaB through the NEMO protein,
      indicating that EDA results from impaired NF-kappaB signaling. Finally, we show
      that abnormal immunity in OL-EDA-ID patients results from impaired cell responses
      to lipopolysaccharide, interleukin (IL)-1beta, IL-18, TNFalpha and CD154. We thus
      report for the first time that impaired but not abolished NF-kappaB signaling in
      humans results in two related syndromes that associate specific developmental and
      immunological defects.

PMID- 11242110
TI  - DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1.
AB  - The DiGeorge/velocardiofacial syndrome (DGS/VCFS) is a relatively common human
      disorder, usually associated with deletions of chromosome 22q11. The genetic
      basis for the wide range of developmental anomalies in the heart, glands and
      facial structures has been elusive. We have investigated the potential role of
      one candidate gene, Tbx1, which encodes a transcription factor of the T-box
      family, by producing a null mutation in mice. We found that mice heterozygous for
      the mutation had a high incidence of cardiac outflow tract anomalies, thus
      modeling one of the major abnormalities of the human syndrome. Moreover, Tbx1-/-
      mice displayed a wide range of developmental anomalies encompassing almost all of
      the common DGS/VCFS features, including hypoplasia of the thymus and parathyroid
      glands, cardiac outflow tract abnormalities, abnormal facial structures, abnormal
      vertebrae and cleft palate. On the basis of this phenotype in mice, we propose
      that TBX1 in humans is a key gene in the etiology of DGS/VCFS.

PMID- 11242111
TI  - Mice lacking the homologue of the human 22q11.2 gene CRKL phenocopy
      neurocristopathies of DiGeorge syndrome.
AB  - Heterozygous deletions within human chromosome 22q11 are the genetic basis of
      DiGeorge/velocardiofacial syndrome (DGS/VCFS), the most common deletion syndrome
      (1 in 4,000 live births) in humans. CRKL maps within the common deletion region
      for DGS/VCFS (ref. 2) and encodes an SH2-SH3-SH3 adapter protein closely related
      to the Crk gene products. Here we report that mice homozygous for a targeted null
      mutation at the CrkL locus (gene symbol Crkol for mice) exhibit defects in
      multiple cranial and cardiac neural crest derivatives including the cranial
      ganglia, aortic arch arteries, cardiac outflow tract, thymus, parathyroid glands
      and craniofacial structures. We show that the migration and early expansion of
      neural crest cells is unaffected in Crkol-/- embryos. These results therefore
      indicate an essential stage- and tissue-specific role for Crkol in the function,
      differentiation, and/or survival of neural crest cells during development. The
      similarity between the Crkol-/- phenotype and the clinical manifestations of
      DGS/VCFS implicate defects in CRKL-mediated signaling pathways as part of the
      molecular mechanism underlying this syndrome.

PMID- 11242112
TI  - A temperature-sensitive disorder in basal transcription and DNA repair in humans.
AB  - The xeroderma pigmentosum group D (XPD) helicase subunit of TFIIH functions in
      DNA repair and transcription initiation. Different mutations in XPD give rise to
      three ultraviolet-sensitive syndromes: the skin cancer-prone disorder xeroderma
      pigmentosum (XP), in which repair of ultraviolet damage is affected; and the
      severe neurodevelopmental conditions Cockayne syndrome (CS) and
      trichothiodystrophy (TTD). In the latter two, the basal transcription function of
      TFIIH is also presumed to be affected. Here we report four unusual TTD patients
      with fever-dependent reversible deterioration of TTD features such as brittle
      hair. Cells from these patients show an in vivo temperature-sensitive defect of
      transcription and DNA repair due to thermo-instability of TFIIH. Our findings
      reveal the clinical consequences of impaired basal transcription and mutations in
      very fundamental processes in humans, which previously were only known in lower
      organisms.

PMID- 11242113
TI  - Chromatin profiling using targeted DNA adenine methyltransferase.
AB  - Chromatin is the highly complex structure consisting of DNA and hundreds of
      associated proteins. Most chromatin proteins exert their regulatory and
      structural functions by binding to specific chromosomal loci. Knowledge of the
      identity of these in vivo target loci is essential for the understanding of the
      functions and mechanisms of action of chromatin proteins. We report here large
      scale mapping of in vivo binding sites of chromatin proteins, using a novel
      approach based on a combination of targeted DNA methylation and microarray
      technology. We show that three distinct chromatin proteins in Drosophila
      melanogaster cells each associate with specific sets of genes. HP1 binds
      predominantly to pericentric genes and transposable elements. GAGA factor
      associates with euchromatic genes that are enriched in (GA)n motifs. A Drosophila
      homolog of Saccharomyces cerevisiae Sir2p is associated with several active genes
      and is excluded from heterochromatin. High-resolution, genome-wide maps of target
      loci of chromatin proteins ('chromatin profiles') provide new insights into
      chromatin structure and gene regulation.

PMID- 11242114
TI  - Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base
      subunit-1, cause hereditary sensory neuropathy type I.
AB  - Hereditary sensory neuropathy type I (HSN1) is the most common hereditary
      disorder of peripheral sensory neurons. HSN1 is an autosomal dominant progressive
      degeneration of dorsal root ganglia and motor neurons with onset in the second or
      third decades. Initial symptoms are sensory loss in the feet followed by distal
      muscle wasting and weakness. Loss of pain sensation leads to chronic skin ulcers
      and distal amputations. The HSN1 locus has been mapped to chromosome 9q22.1-22.3
      (refs. 3,4). Here we map the gene SPTLC1, encoding serine palmitoyltransferase,
      long chain base subunit-1, to this locus. Mutation screening revealed 3 different
      missense mutations resulting in changes to 2 amino acids in all affected members
      of 11 HSN1 families. We found two mutations to be located in exon 5 (C133Y and
      C133W) and one mutation to be located in exon 6 of SPTLC1 (V144D). All families
      showing definite or probable linkage to chromosome 9 had mutations in these two
      exons. These mutations are associated with increased de novo glucosyl ceramide
      synthesis in lymphoblast cell lines in affected individuals. Increased de novo
      ceramide synthesis triggers apoptosis and is associated with massive cell death
      during neural tube closure, raising the possibility that neural degeneration in
      HSN1 is due to ceramide-induced apoptotic cell death.

PMID- 11242115
TI  - Constitutively activating mutation in WASP causes X-linked severe congenital
      neutropenia.
AB  - The Wiskott-Aldrich syndrome protein (WASP; encoded by the gene WAS) and its
      homologs are important regulators of the actin cytoskeleton, mediating
      communication between Rho-family GTPases and the actin nucleation/crosslinking
      factor, the Arp2/3 complex. Many WAS mutations impair cytoskeletal control in
      hematopoietic tissues, resulting in functional and developmental defects that
      define the X-linked Wiskott-Aldrich syndrome (WAS) and the related X-linked
      thrombocytopenia (XLT). These diseases seem to result from reduced WASP
      signaling, often through decreased transcription or translation of the gene. Here
      we describe a new disease, X-linked severe congenital neutropenia (XLN), caused
      by a novel L270P mutation in the region of WAS encoding the conserved GTPase
      binding domain (GBD). In vitro, the mutant protein is constitutively activated
      through disruption of an autoinhibitory domain in the wild-type protein,
      indicating that loss of WASP autoinhibition is a key event in XLN. Our findings
      highlight the importance of precise regulation of WASP in hematopoietic
      development and function, as impairment versus enhancement of its activity give
      rise to distinct spectra of cellular defects and clinical phenotypes.

PMID- 11242116
TI  - Episodic evolution of pyrin in primates: human mutations recapitulate ancestral
      amino acid states.
AB  - Familial Mediterranean fever (FMF; MIM 249100) is an autosomal recessive disease
      characterized by recurrent attacks of fever with synovial, pleural or peritoneal
      inflammation. The disease is caused by mutations in the gene encoding the pyrin
      protein. Human population studies have revealed extremely high allele frequencies
      for several different pyrin mutations, leading to the conclusion that the mutant
      alleles confer a selective advantage. Here we examine the ret finger protein
      (rfp) domain (which contains most of the disease-causing mutations) of pyrin
      during primate evolution. Amino acids that cause human disease are often present
      as wild type in other species. This is true at positions 653 (a novel mutation),
      680, 681, 726, 744 and 761. For several of these human mutations, the mutant
      represents the reappearance of an ancestral amino acid state. Examination of
      lineage-specific dN/dS ratios revealed a pattern consistent with the signature of
      episodic positive selection. Our data, together with previous human population
      studies, indicate that selective pressures may have caused functional evolution
      of pyrin in humans and other primates.

PMID- 11242117
TI  - A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett
      syndrome.
AB  - Rett syndrome (RTT) is an inherited neurodevelopmental disorder of females that
      occurs once in 10,000-15,000 births. Affected females develop normally for 6-18
      months, but then lose voluntary movements, including speech and hand skills. Most
      RTT patients are heterozygous for mutations in the X-linked gene MECP2 (refs. 3
      12), encoding a protein that binds to methylated sites in genomic DNA and
      facilitates gene silencing. Previous work with Mecp2-null embryonic stem cells
      indicated that MeCP2 is essential for mouse embryogenesis. Here we generate mice
      lacking Mecp2 using Cre-loxP technology. Both Mecp2-null mice and mice in which
      Mecp2 was deleted in brain showed severe neurological symptoms at approximately
      six weeks of age. Compensation for absence of MeCP2 in other tissues by MeCP1
      (refs. 19,20) was not apparent in genetic or biochemical tests. After several
      months, heterozygous female mice also showed behavioral symptoms. The overlapping
      delay before symptom onset in humans and mice, despite their profoundly different
      rates of development, raises the possibility that stability of brain function,
      not brain development per se, is compromised by the absence of MeCP2.

PMID- 11242118
TI  - Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like
      phenotype in mice.
AB  - Mecp2 is an X-linked gene encoding a nuclear protein that binds specifically to
      methylated DNA (ref. 1) and functions as a general transcriptional repressor by
      associating with chromatin-remodeling complexes. Mecp2 is expressed at high
      levels in the postnatal brain, indicating that methylation-dependent regulation
      of gene expression may have a crucial role in the mammalian central nervous
      system. Consistent with this notion is the recent demonstration that MECP2
      mutations cause Rett syndrome (RTT, MIM 312750), a childhood neurological
      disorder that represents one of the most common causes of mental retardation in
      females. Here we show that Mecp2-deficient mice exhibit phenotypes that resemble
      some of the symptoms of RTT patients. Mecp2-null mice were normal until 5 weeks
      of age, when they began to develop disease, leading to death between 6 and 12
      weeks. Mutant brains showed substantial reduction in both weight and neuronal
      cell size, but no obvious structural defects or signs of neurodegeneration. Brain
      specific deletion of Mecp2 at embryonic day (E) 12 resulted in a phenotype
      identical to that of the null mutation, indicating that the phenotype is caused
      by Mecp2 deficiency in the CNS rather than in peripheral tissues. Deletion of
      Mecp2 in postnatal CNS neurons led to a similar neuronal phenotype, although at a
      later age. Our results indicate that the role of Mecp2 is not restricted to the
      immature brain, but becomes critical in mature neurons. Mecp2 deficiency in these
      neurons is sufficient to cause neuronal dysfunction with symptomatic
      manifestation similar to Rett syndrome.

PMID- 11242119
TI  - Open-reading-frame sequence tags (OSTs) support the existence of at least 17,300
      genes in C. elegans.
AB  - The genome sequences of Caenorhabditis elegans, Drosophila melanogaster and
      Arabidopsis thaliana have been predicted to contain 19,000, 13,600 and 25,500
      genes, respectively. Before this information can be fully used for evolutionary
      and functional studies, several issues need to be addressed. First, the gene
      number estimates obtained in silico and not yet supported by any experimental
      data need to be verified. For example, it seems biologically paradoxical that C.
      elegans would have 50% more genes than Drosophilia. Second, intron/exon
      predictions need to be tested experimentally. Third, complete sets of open
      reading frames (ORFs), or "ORFeomes," need to be cloned into various expression
      vectors. To address these issues simultaneously, we have designed and applied to
      C. elegans the following strategy. Predicted ORFs are amplified by PCR from a
      highly representative cDNA library using ORF-specific primers, cloned by Gateway
      recombination cloning and then sequenced to generate ORF sequence tags (OSTs) as
      a way to verify identity and splicing. In a sample (n=1,222) of the nearly 10,000
      genes predicted ab initio (that is, for which no expressed sequence tag (EST) is
      available so far), at least 70% were verified by OSTs. We also observed that 27%
      of these experimentally confirmed genes have a structure different from that
      predicted by GeneFinder. We now have experimental evidence that supports the
      existence of at least 17,300 genes in C. elegans. Hence we suggest that gene
      counts based primarily on ESTs may underestimate the number of genes in human and
      in other organisms.

PMID- 11242120
TI  - Homology-based annotation yields 1,042 new candidate genes in the Drosophila
      melanogaster genome.
AB  - The approach to annotating a genome critically affects the number and accuracy of
      genes identified in the genome sequence. Genome annotation based on stringent
      gene identification is prone to underestimate the complement of genes encoded in
      a genome. In contrast, over-prediction of putative genes followed by exhaustive
      computational sequence, motif and structural homology search will find rarely
      expressed, possibly unique, new genes at the risk of including non-functional
      genes. We developed a two-stage approach that combines the merits of stringent
      genome annotation with the benefits of over-prediction. First we identify
      plausible genes regardless of matches with EST, cDNA or protein sequences from
      the organism (stage 1). In the second stage, proteins predicted from the
      plausible genes are compared at the protein level with EST, cDNA and protein
      sequences, and protein structures from other organisms (stage 2). Remote but
      biologically meaningful protein sequence or structure homologies provide
      supporting evidence for genuine genes. The method, applied to the Drosophila
      melanogaster genome, validated 1,042 novel candidate genes after filtering 19,410
      plausible genes, of which 12,124 matched the original 13,601 annotated genes.
      This annotation strategy is applicable to genomes of all organisms, including
      human.

PMID- 11242121
TI  - Maternal methylation imprints on human chromosome 15 are established during or
      after fertilization.
AB  - Prader-Willi syndrome (PWS) is a neurogenetic disorder that results from the lack
      of transcripts expressed from the paternal copy of the imprinted chromosomal
      region 15q11-q13 (refs. 1,2). In some patients, this is associated with a
      deletion of the SNURF-SNRPN exon 1 region inherited from the paternal grandmother
      and the presence of a maternal imprint on the paternal chromosome. Assuming that
      imprints are reset in the germ line, we and others have suggested that this
      region constitutes part of the 15q imprinting center (IC) and is important for
      the maternal to paternal imprint switch in the male germ line. Here we report
      that sperm DNA from two males with an IC deletion had a normal paternal
      methylation pattern along 15q11-q13. Similar findings were made in a mouse model.
      Our results indicate that the incorrect maternal methylation imprint in IC
      deletion patients is established de novo after fertilization. Moreover, we found
      that CpG-rich regions in SNURF-SNRPN and NDN, which in somatic tissues are
      methylated on the maternal allele, are hypomethylated in unfertilized human
      oocytes. Our results indicate that the normal maternal methylation imprints in
      15q11-q13 also are established during or after fertilization.

PMID- 11242124
TI  - The effect of Bcl-2 adenovirus against murine hepatocyte apoptosis caused by
      tumor necrosis factor alpha and D-galactosamine.
AB  - OBJECTIVE: To evaluate the role of Bcl-2 family proteins in hepatic apoptosis
      caused by TNF-alpha and D-galactosamine. METHODS: We induced mouse liver injury
      with TNF-alpha and D-galactosamine, and detected hepatic apoptosis, the
      expression of Bcl-2, Bax, and Bak proteins on hepatocytes by using TUNEL or
      immunohistochemistry, respectively. We also observed the expression of Bcl-2
      protein on hepatocytes infected with Bcl-2 adenovirus vector and its protection
      against hepatocyte apoptosis. RESULTS: Hepatocyte apoptosis was induced in BalB/c
      mice pretreated with TNF-alpha plus D-galactosamine, accompanying the enhanced
      expression of Bax, Bak proteins in hepatocytes. Bcl-2 protein was expressed in
      murine hepatocytes and lasted at least 1 month after injection of Bcl-2
      adenovirus vector, which also lowered ALT level from (1372.9+/-251.4)U/L to
      (796.5+/-78.7)U/L and reduced hepatocyte apoptosis caused by TNF-alpha and D
      galactosamine. CONCLUSIONS: The enhanced expression of Bax, Bak proteins may play
      a role in hepatocyte apoptosis induced by TNF-alpha and D-galactosamine. D
      galactosamine adenovirus vector can partially reduced hepatocyte apoptosis
      induced by TNF- alpha and D-galactosamine.

PMID- 11242125
TI  - mRNA and protein expression of Fas associated death domain protein in apoptosic
      hepatocyte induced by tumor necrosis factor-alpha.
AB  - OBJECTIVE: To study the expression of protein and mRNA of Fas associated death
      domain protein (FADD) in the apoptosic hepatocyte induced by D-galactosamine
      (GalN) and TNF-alpha. METHODS: Fulminant hepatic failure (FHF) was induced by
      injection of GalN into sensitized BALB/c mice by TNF-alpha. Hepatocyte apoptosis
      was examined by electric microscopy, in site end labeling (ISEL) and DNA
      electrophoresis on 1.5% agarose gel. The expression of protein and mRNA of FADD
      were detected by immunohistochemistry and PT-PCR. RESULTS: GalN/TNF-alpha may
      induce hepatocyte apoptosis, necrosis and liver failure. The expression of
      protein and mRNA of FADD were positively correlative with the apoptosic
      hepatocytes. CONCLUSION: TNF-alpha induces hepatocyte apoptosis by up regulation
      expression of FADD protein.

PMID- 11242126
TI  - Development and application of the serological assay for humoral immune response
      against duck hepatitis B virus.
AB  - OBJECTIVE: To develop a simple and specific assay for detection of humoral immune
      response in duck hepatitis B virus (DHBV) infected ducks. METHODS: Eighty serum
      samples were detected by ELISA for DHBsAg with prepared anti-preS 1H1 ascitic
      fluid and by PCR or dot blot hybridization for DHBV DNA. Thirty-two serum samples
      from experimentally infected 1-day-old ducks were assayed by ELISA for DHBcAb and
      DHBsAb. RESULTS: Of 66 PCR positive samples, 58 were positive for DHBsAg and 62
      were positive for DHBV dot blot hybridization. Sensitivities of the two methods
      were 87.9% and 93.9%, respectively. Anti-DHBc was developed in 2/8 infected ducks
      at day 21 but negative after day 28. Anti-DHBs antibodies were negative
      throughout the infectious period. CONCLUSION: The application of DHBV infection
      and serological assay will be helpful to the study of kinetics of DHBV and
      humoral immune response of ducks against the virus.

PMID- 11242127
TI  - The role of Kupffer cells in non-alcoholic steatohepatitis of rats chronically
      fed with high-fat diet.
AB  - OBJECTIVE: To explore the role of Kupffer cells in non-alcoholic steatohepatitis
      (NASH) by means of rat model. METHODS: Nineteen male SD rats were randomized into
      model group (n=10) and normal group (n=9), with a high-fat diet and standard diet
      for 12 weeks, respectively. Routine histologic features of hepatic section were
      observed by HE staining. The number and shape of Kupffer cells in the liver were
      detected by immunohistochemistry and penetrated electron microscope,
      respectively. RESULTS: All rats of model group developed NASH, which was
      characterized by obesity and hyperlipidemia. Histopathological examination showed
      hepatocellular macrovesicular steatosis, lobular inflammatory cell infiltration
      and necrosis. Compared with normal group, the count of Kupffer cells in the liver
      was largely increased, and the Kupffer cells in the model group were activated to
      some extent. Furthermore, these changes of Kupffer cells were in accordance with
      the degree of steatosis, inflammation and necrosis in the liver of the model
      group. CONCLUSION: The number and activity of Kupffer cells are increased
      significantly in NASH induced by high-fat diet, and Kupffer cells might be
      involved in the pathogenesis of steatohepatitis.

PMID- 11242128
TI  - Hepatitis B virus transgenic mice for the model of anti-hepatitis B virus drug
      study.
AB  - OBJECTIVE: To establish hepatitis B virus (HBV) transgenic mice models and to
      investigate if the model can be used for the evaluation of anti-HBV drugs.
      METHODS: HBV transgenic mice models were produced by microinjection to analyze
      the integration, expression of HBV in the transgenic mice by nested PCR, southern
      blot, immunohistochemistry, and ELISA. Sixty mice whose HBV DNA, HBsAg were
      positive were divided into 6 groups randomly, in which 3 groups were given drugs:
      lamivudine administrated by perfusion of stomach tube (100mg x kg(-1) x day(-1)
      for 21 days); thymosine administrated by abdomen injection (3mg x day(-1) for 90
      days); and DNA vaccine of 100 microg by muscle injection. The other 3 groups were
      negative control. RESULTS: Lamivudine, thymosine and DNA vaccine made HBV DNA
      become negative in the serum of HBV transgenic mice. The negative ratio was
      highest in lamivudine treatment group. HBV DNA became positive again when
      lamivudine terminated. CONCLUSION: Limvudine, thymosine, and DNA vaccine can
      inhibit HBV replication. Transgenic mice might be used as the model for anti-HBV
      drug screening and evaluation.

PMID- 11242129
TI  - Phosphorylation of hepatic stimulator substance on mitogen-activated protein
      kinase in BEL-7402 hepatoma cells.
AB  - OBJECTIVE: To obtain more insight into information of signal transduction of EGF
      receptor-mediated pathway response to the stimulation of hepatic stimulator
      substance (HSS). METHODS: HSS was extracted from weanling rat liver and partially
      purified. Bioactivity of HSS was confirmed with its ability to proliferate
      hepatoma cell in vitro. Meanwhile, a rat recombinant HSS vector was constructed
      and expressed in BL-21 E. Coli. Mitogen-activated protein kinase (MAPK)
      activation marked by phosphorylation at Thr202/Tyr204 was determined by Western
      blot. RESULTS: The molecular weight of the biochemically purified HSS was found
      identically to that of the recombined HSS as expressed in the prokaryotic cells.
      After the treatment of HSS, cellular MAPK phosphorylation was initiated obviously
      at 15 min and maintained to 30 min. In comparison with EGF, MAPK phosphorylation
      as stimulated by HSS appeared less intensive and later time-kinetics as well. The
      HSS induction on cellular MAPK phosphorylation was gradually inhibited by
      PD98059, a specific inhibitor of MAPK kinase (MEK). A complete blockade was seen
      at 100 micromol/L of PD98059. CONCLUSIONS: The involvement of HSS on MAPK
      activation implies that this liver-specific growth factor might take part in,
      either individually or as combined with other growth factors, the regulation of
      TPK signaling cascade during hepatocyte proliferation.

PMID- 11242130
TI  - Investigation on the rheological properties of hepatocellular carcinoma cells and
      their relevance to cytoskeleton structure.
AB  - OBJECTIVE: To investigate the relevance of the rheological properties, i.e.,
      viscoelasticities and adhesion to basement membrane components coated surface, of
      both hepatocytes and hepatocellular carcinoma (HCC) cells to the cytoskeleton
      structure. METHODS: Micropipette aspiration technique was adopted to measure
      viscoelastic coefficients and adhesion forces to 2 microg/ml collagen IV/1.25
      microg/ml laminin coated surface of the cells. Two kinds of cytoskeleton
      perturbing agents, colchicine and cytochalasin D, were used to treat both HCC
      cells and hepatocytes and the effects of these treatments on cell viscoelastic
      coefficients and cell adhesion forces were investigated. RESULTS: Upon treatment
      of cells with colchicine in a concentration range of 1 to 60 mg/L, the elastic
      coefficients, especially the first elastic coefficient K1, and adhesion forces of
      hepatocytes generally tended to increase or increased significantly while, in
      contrast, viscoelastic coefficients and adhesion forces of HCC cells decreased
      obviously. Upon treatment of cells with cytochalasin D in a concentration range
      of 0.25-5.00 mg/L, viscoelastic coefficients of both hepatocytes and HCC cells
      decreased uniformly, with a larger magnitude for the decrease in elastic
      coefficients and adhesion forces of HCC cells than for those of hepatocytes.
      Adhesion forces of hepatocytes and HCC cells onto collagen IV/laminin coated
      surface varied similarly as viscoelastic coefficients under the action of the
      cytoskeleton perturbing agents. A significant positive correlation existed
      between changes of HCC cell adhesion forces on collagen IV/laminin coated
      surfaces and those of cell elastic coefficients (P<0.01). CONCLUSIONS: The
      effects of cochicine and cytochalasin D on rheological properties of HCC cells
      differed significantly either in ways or extents from those on rheological
      properties of hepatocytes. These results might reflect the difference in the
      state of cytoskeleton structure and function among these two kinds of cells.

PMID- 11242131
TI  - The effect of attenuated varicella-zoster virus on replication of HBV.
AB  - OBJECTIVE: To observe the effect of attenuated varicella-zoster virus (VZV) on
      replication of HBV in vitro and vivo. METHODS: The attenuated VZV were inoculated
      into the ducks infected with DHBV and into the cultural HepG(2) 2.2.15 cells,
      respectively. DHBV DNA, HBsAg and HBeAg were detected from the duck serum and
      cell cultural fluid by dot-blot hybridization and EIA. RESULTS: The decline of
      DHBV DNA in duck serum was found in two dosage groups. Compared with pre
      treatment, the level of AD value in 200 pfu/kg group was significantly decreased
      from 1.17+/-0.29 to 0.59+/-0.45 (10 day after VZV treatment) and 0.21+/-0.21 (5
      day after withdrawal of VZV)(t =3.51, 7.54, P<0.001). The level in 400 pfu/kg
      group was from 0.70+/-0.25 to 0.32+/-0.17 on the 5th day of withdrawal of VZV (t
      =3.58, P<0.01), respectively after treatment. The inhibitory rates of HBeAg and
      HBsAg were 61% and 33%, respectively. The effect on HBeAg seems to be more
      obvious than on HBsAg. CONCLUSIONS: Attenuated VZV could significantly decrease
      serum DHBV DNA in DHBV-infected ducks and directly inhibit the HBeAg and HBsAg
      secreted by 2.2.15 cells, suggesting that VZV seems to interfere or inhibit the
      replication of DHBV.

PMID- 11242132
TI  - Hepatitis C virus infection and morphologic study in B lymphocytes of patient
      with hepatitis C.
AB  - OBJECTIVE: To study hepatitis C virus (HCV) infection in B lymphocytes of
      patients with hepatitis C and to establish a B cell line with HCV infection and
      observe the hepatitis C virus like particles. METHODS: A B lymphoblastoid cell
      line was established by Epstein-Barr virus induced transformation directly from
      peripheral blood mononuclear cells of a patient with hepatitis C. The HCV antigen
      and HCV RNA were detected by immunohistochemical technique. Reverse transcription
      polymerase chain reaction(RT-PCR) and in situ hybridization and HCV particle were
      detected by electron microscopy. RESULTS: Positive HCV RNA was found in
      supernatants of B cell line. HCV Ag and HCV RNA were also showed positive.
      Electron microscopy observed HCV spherical virus like particles with a diameter
      of approximately 65 nm and 110 nm and the "bud mutation" of HCV in the
      cytoplasmic vesicles of B lymphocytes. CONCLUSIONS: HCV could infect B
      lymphocytes and replicate in the cell line. HCV particles are formed by "bud
      mutation" of HCV in the cytoplasmic vesicles of B-lymphocytes.

PMID- 11242133
TI  - Clinical characteristics of the patients with hepatitis B combining hepatitis D
      infection.
AB  - OBJECTIVE: To explore the pathogenesis of hepatitis D virus by analyzing the
      clinic characteristics of 507 cases of hepatitis B (HB) with hepatitis D virus
      (HDV) infection. METHODS: The occurrence of different types of hepatitis, the
      prognosis, clinical features, major biochemistry results, and hepatitis virus
      marks were analyzed in 507 cases of HB with positive HDV and compared with 213
      cases of HB with negative HDV. RESULTS: The incidence and the mortality of
      serious chronic hepatitis, severe hepatitis, and liver cirrhosis were all higher
      in the HB patients with positive HDV than negative one. The incidence of
      bleeding, ascites, hepat-coma complication, and the level of ALT were higher in
      HDV-positive patients than in HDV-negative patients (P<0.01 or P<0.05), and the
      changes of the major biochemistry results were more obvious than the same types
      of hepatitis B with negative HDV (P<0.01). The detection rate for HBeAg in serum
      of the patients positive for HDV was obviously lower than that of the patients
      negative for HDV(P<0.01). In patients with acute hepatitis, severe hepatitis, and
      liver cirrhosis, the expression of positive HDAg and negative HBeAG was obviously
      higher than that of positive HDAg and HBeAg (P<0.01 or P<0.05). CONCLUSIONS:
      After HDV infection, the incidences and poor prognosis of serious chronic
      hepatitis, severe hepatitis, and liver cirrhosis increase. HDV infection can
      inhibit the replication of HBV DNA or HBeAg expression. The effects of direct
      cytotoxicity of HDV on hepatocytes may play a major pathogenic role in acute
      hepatitis and in aggravating illness status to severe type.

PMID- 11242134
TI  - Study of iron metabolism abnormality in the hepatocyte damage of hepatitis B.
AB  - OBJECTIVE: To study the effect of iron metabolism on patients with hepatitis B.
      METHODS: Hemoglobin (Hb), serum ferritin (SF), transferritin (TRF), serum iron
      (SI), and total iron binding capacity (TIBC) were detected in 103 patients with
      hepatitis B and 20 healthy adults. RESULTS: The severer the hepatocyte damage
      was, the higher the SF, SI and the lower the Hb, TRF, and TIBC were. Furthermore,
      it seems more obvious among fulminant hepatitis and liver cirrhosis. CONCLUSIONS:
      The overload of iron may enhance the hepatocyte damage induced by HBV. Therefore,
      to detect serum markers of iron metabolism is helpful to evaluate curative effect
      and prognosis of hepatitis B.

PMID- 11242135
TI  - Changes and significance of circulating hepatocellular carcinoma cells in
      recurrent hepatocellular carcinoma patients after combined treatment.
AB  - OBJECTIVE: To study the changes and significance of circulating hepatocellular
      carcinoma cells in recurrent hepatocellular carcinoma (HCC) patients after
      combined treatment of transarterial chemo-embolization(TACE) and percutaneous
      ethanol injection(PEI). METHODS: We detected 19 blood samples from the recurrent
      HCC patients by nested RT-PCR to find out AFP mRNA before and after the
      treatment. RESULTS: There were 7 patients with AFP mRNA positive before treatment
      (36.8%), and none of patients with AFP mRNA positive after treatment.
      CONCLUSIONS: Combined treatment of TACE and PEI can effectively eliminate
      circulating hepatocellular carcinoma cells and thereby prevent metastasis and
      recurrence of HCC.

PMID- 11242136
TI  - Genetic mutations of precore region of hepatitis B virus in hepatitis B e antigen
      negative patients with fulminant hepatitis B and translation of precore variants
      in vitro.
AB  - OBJECTIVE: To detect mutations in precore region of hepatitis B virus of HBeAg
      negative- patients with fulminant hepatitis and to determine the effect of T1862
      mutants on synthesis of precursor of hepatitis B e antigen. METHODS: The entire
      precore and core region were amplified from sera of nine HBeAg negative-patients
      with fulminant hepatitis B by polymerase chain reaction (PCR). PCR products were
      cloned into plasmid pUC18, and sequencing for analysis of precore mutations.
      Precore and core sequence of T1862 variant were also cloned into expression
      plasmid pGEMT for in vitro transcription and translation study on synthesis and
      procession of e antigen. RESULTS: Three variants, A1896, A1899 and T1862, whose
      nucleotide mutation led to amino acids substitutions, were detected in patients
      with fulminant hepatitis. T1862 variant didn't effect the synthesis of precursor
      of e antigen. Also there was no variant detected in precore region of hepatitis B
      virus in two patients. CONCLUSIONS: The causes for negative of e antigen in
      fulminant hepatitis patients may be partially explained by precore mutation of
      A1896 and T1862, and the latter variant may effect the process of precursor of e
      antigen, rather than the synthesis of precursor protein.

PMID- 11242137
TI  - Oral contraceptives in the treatment of acne.
AB  - Oral contraceptives (OCs) can reduce acne by lowering the production of adrenal
      and ovarian androgens, by inhibiting 5-alpha-reductase, which in turn, reduces
      the levels of dihydrotestosterone, and by stimulating sex hormone binding
      globulin (SHBG), thus reducing the levels of free testosterone. In newer OCs,
      such as Tricyclen and Diane-35, the progestin component is minimally androgenic
      and anti-androgenic respectively, thereby enhancing the favorable profile of
      these products in the treatment of hyperandrogenic disorders, including acne. The
      efficacy of these agents and their long-term safety profile supports their use in
      various grades of acne in females: * As adjunctive therapy to topical agents for
      women with mild non-scarring acne desiring oral contraception * As primary
      therapy for patients with moderate non-scarring acne in combination with topical
      therapy and systemic antibiotics * As one of two preferred methods of
      contraception in patients with scarring and severe inflammatory acne being
      treated with systemic isotretinoin.

PMID- 11242138
TI  - Drug treatments for skin disease introduced in 2000.

PMID- 11242139
TI  - The HIV-1 transactivator protein Tat is a potent inducer of the human DNA repair
      enzyme beta-polymerase.
AB  - OBJECTIVE: This study examines the effects of the HIV-1 regulatory proteins, Tat
      and Rev, on the expression of the DNA polymerase beta (beta-pol) gene, which
      encodes a key protein in the DNA base-excision repair pathway. The rationale for
      these experiments is to examine the potential involvement of base-excision repair
      protein deregulation in HIV-1-related lymphomas. DESIGN: Expression of beta-pol
      mRNA was examined in AIDS-related lymphomas and non-AIDS-related lymphomas and as
      a function of HIV-1 infection of B cells in culture. The effect of Tat or Rev
      over-expression on beta-pol promoter expression was tested by transient co
      transfection assays with a beta-pol promoter reporter plasmid and a Tat or Rev
      over-expression plasmid. METHODS: Northern blot analysis was used to quantitate
      beta-pol expression in lymphoma and cells. Raji cells were co-transfected with a
      chloramphenicol acetyltransferase (CAT) reporter plasmid and a plasmid over
      expressing Tat or Rev. CAT activity was measured in transfected cells. RESULTS:
      beta-Pol mRNA was > 10-fold higher in AIDS-related than in non-AIDS B-lineage
      lymphomas. beta-Pol expression was up-regulated in a B-cell line upon infection
      with HIV-1, and increased in Raji cells upon recombinant expression of the Tat
      gene. The beta-pol promoter was transactivated (fourfold induction) by Tat, but
      not by Rev. Tat-dependent transactivation required a binding site for the
      transcription factor Sp1 in the beta-pol promoter. CONCLUSION: These results
      suggest that HIV-1 Tat can interact with cellular transcription factors to
      increase the steady-state level of beta-pol in B cells. Tat-mediated induction of
      beta-pol may alter DNA stability in AIDS-related lymphomas.

PMID- 11242140
TI  - Myeloid-related protein (MRP)-8 from cervico-vaginal secretions activates HIV
      replication.
AB  - OBJECTIVES: To identify a substance found in female genital tract secretions that
      enhances HIV expression in infected cells. DESIGN: Cervico-vaginal lavages (CVL),
      collected in sterile normal saline, were fractionated and tested for HIV-inducing
      activity using HIV-infected monocytes. METHODS: To purify the component(s) of CVL
      that enhance HIV production, Mono-Q ion exchange chromatography followed by
      Superose-12 molecular sieve analysis, and SDS--PAGE were performed. The purified
      protein was identified by amino acid sequence analysis. RESULTS: SDS--PAGE of
      bioactive fractions showed a 14 kDa polypeptide band. Amino acid sequence
      analysis of selected peptides from the 14 kDa band showed 100% homology with the
      myeloid-related protein (MRP)-8, an inflammatory protein found in mucosal
      secretions. Western blot analysis revealed that bioactive CVL contained more
      immunoreactive MRP-8 than samples without bioactivity. The HIV-inducing activity
      of MRP-8 was further confirmed by showing that human recombinant MRP-8 increased
      HIV expression by up to 40-fold. CONCLUSIONS: MRP-8 in cervico-vaginal secretions
      stimulates HIV production. Strategies aimed at blocking MRP-8 activity in the
      genital tract could reduce risk of sexual as well as maternal--infant
      transmission of HIV.

PMID- 11242141
TI  - Clinical correlation of variations in the internal transcribed spacer regions of
      rRNA genes in Pneumocystis carinii f.sp. hominis.
AB  - OBJECTIVES: To analyse the importance of sequence variations in the internal
      transcribed spacer (ITS) regions 1 and 2 of the nuclear rRNA operon in AIDS
      patients with Pneumocystis carinii pneumonia (PCP). DESIGN AND METHODS: ITS 1 and
      2 genotypes were determined in 162 bronchoalveolar lavage samples from 130
      patients participating in a prospective cohort study of PCP. RESULTS: A total of
      49 different ITS genotypes were detected. ITS genotype was not associated with
      the clinical severity or outcome of PCP. In 37 of 162 (23%) samples infection
      with two or more genotypes was observed. A genotype switch was detected in six of
      10 patients (60%) with recurrent episodes of PCP. However, genotype changes were
      also seen in 10 of 19 patients (53%) who had repeated bronchoscopies within the
      same episode of PCP. The same ITS type was observed twice in 13 (46%) of the 28
      patients with repeat bronchoscopies during single or recurrent episodes of
      pneumonia, but in only 14 of 81 (17%) randomly selected pairs (P < 0.01).
      CONCLUSION: Although the detection of ITS genotypes is not a random event,
      changes in genotype can be detected in a single episode of disease, with 23% of
      PCP patients being infected with more than one P. carinii genotype, thus
      complicating the use of this locus as a genetic marker to separate new infection
      from the reactivation of latent infection. ITS genotypes are not associated with
      the clinical severity of PCP.

PMID- 11242142
TI  - Genetic diversity of Pneumocystis carinii in HIV-positive and -negative patients
      as revealed by PCR-SSCP typing.
AB  - OBJECTIVE: To describe the epidemiology of severe Pneumocystis carinii pneumonia
      (PCP) in HIV-infected and non HIV-infected patients. METHODS: Bronchoalveolar
      lavage specimens from 212 European patients with PCP were typed using PCR--single
      strand conformation polymorphism analysis of four genomic regions of P. carinii
      f. sp. hominis. Demographic and clinical information was obtained from all
      patients. RESULTS: Twenty-three per cent of the patients were presumably infected
      with a single P. c. hominis type. The other patients presented with two (50%) or
      more (27%) types. Thirty-five genetically stable and ubiquitous P. c. hominis
      types were found. Their frequency ranged from 0.4% to 10% of all isolates, and up
      to 15% of those from a given hospital. There was no significant association
      between the P. c. hominis type or number of co-infecting types per patient and
      geographical location, year of collection, sex, age, or HIV status. No more than
      three patients infected with the same type were observed in the same hospital
      within the same 6 month period, and no epidemiological link between the cases was
      found. CONCLUSIONS: The broad diversity of types observed seems to indicate that
      multiple sources of the pathogen co-exist. There was no evidence that in our
      study population inter-human transmission played a significant role in the
      epidemiology of P. carinii.

PMID- 11242143
TI  - HIV-1-related pleural tuberculosis: elevated production of IFN-gamma, but failure
      of immunity to Mycobacterium tuberculosis.
AB  - BACKGROUND: Pleural tuberculosis can resolve spontaneously, suggesting that the
      inflammatory process may represent a protective immune response. However, pleural
      tuberculosis is strongly associated with HIV infection. It has been suggested
      that cell-mediated immune responses may be reduced, and direct bacterial invasion
      may have a role in pathogenesis, in HIV-positive cases. To test this hypothesis,
      we compared production of the pro-inflammatory cytokines, interferon (IFN)-gamma
      and tumour necrosis factor(TNF)-alpha, production of the immunosuppressive
      cytokine, interleukin (IL)-10, and mycobacterial culture positivity, in HIV
      negative and HIV-positive patients with pleural tuberculosis. METHODS: Cytokine
      levels were measured in serum and pleural fluid, and in supernatants of blood and
      pleural fluid stimulated in vitro using mycobacterial antigens. Intracellular IFN
      gamma and TNF-alpha production was measured after stimulation with phorbol
      myristate acetate and ionomycin in vitro. RESULTS: IFN-gamma was strikingly
      elevated in serum and pleural fluid in HIV-positive, compared to HIV-negative
      subjects (P < or = 0.02). TNF-alpha was elevated, but this was not statistically
      significant. IL-10 levels were higher in serum (P < 0.001), but similar in
      pleural fluid. IFN-gamma responses to soluble mycobacterial antigen in vitro were
      reduced in peripheral blood (P = 0.006), but not pleural fluid, of HIV-positive
      subjects. Intracellular cytokine staining suggested that CD8+ T cells were a
      major source of IFN-gamma in HIV-positive subjects. The proportion of subjects
      with a positive culture for Mycobacterium tuberculosis from pleural fluid was
      higher in the HIV-positive group. CONCLUSIONS: HIV-positive patients with pleural
      tuberculosis show elevated production of IFN-gamma, for which CD8+ T cells may be
      a major source. Mycobacterium tuberculosis can proliferate despite high levels of
      pro-inflammatory cytokines.

PMID- 11242144
TI  - Altered expression of CD43-hexasaccharide isoform on peripheral T lymphocytes
      from HIV-infected individuals.
AB  - OBJECTIVE: To examine if peripheral T lymphocytes from HIV-infected individuals
      show abnormalities in the surface expression of CD43, the major sialoglycoprotein
      of leukocytes. DESIGN: A series of 86 HIV-positive individuals was studied. The
      subjects, grouped by their peripheral CD4 cell count, were in different stages of
      the disease as defined by the Centers for Disease Control and Prevention (CDC).
      METHODS: Peripheral leukocytes and isolated lymphocytes were examined by double
      and triple immunofluorescence flow cytometric and Western blot analyses with
      monoclonal antibodies, which discriminate between CD43 isoforms. RESULTS: We
      found elevated percentages of the surface expression of CD43-hexasaccharide
      isoform on T lymphocytes from 82 out of 86 individuals tested. Increasing
      percentages are progressively found in CDC groups 1, 2 and 3 patients. The
      expression of the molecule is remarkably biased towards the CD8 cell
      subpopulation. The percentage of cells bearing human leukocyte antigen-DR locus
      molecules (HLA-DR) is also augmented. Two subsets expressing T305 have been
      identified: a minor subset that co-expresses HLA-DR and T305; and a second
      population formed by the majority of T305-positive cells, which lack surface HLA
      DR. Finally, we found CD43 bands with altered electrophoretic mobility in lysates
      from peripheral lymphocytes from all HIV-positive individuals tested. CONCLUSION:
      The augmented expression of CD43-hexasaccharides and the observed cellular
      distribution suggest an important regulatory role for this molecule in HIV
      specific responses.

PMID- 11242145
TI  - Assessment of active transport of HIV protease inhibitors in various cell lines
      and the in vitro blood--brain barrier.
AB  - OBJECTIVE: To investigate the involvement of P-glycoprotein (Pgp) and the
      multidrug resistance-associated protein (MRP) on the active transport of the HIV
      protease inhibitors amprenavir, ritonavir and indinavir. METHODS: The transport
      behaviour of ritonavir, indinavir and amprenavir in the presence and absence of
      Pgp modulators and probenecid was investigated in an in vitro blood--brain
      barrier (BBB) co-culture model and in monolayers of LLC-PK1, LLC-PK1:MDR1, LLC
      PK1:MRP1 and Caco-2 cells. RESULTS: All three HIV protease inhibitors showed
      polarized transport in the BBB model, LLC-PK1:MDR1 and Caco-2 cell line. The Pgp
      modulators SDZ-PSC 833, verapamil and LY 335979 inhibited polarized transport,
      although their potency was dependent on both the cell model and the HIV protease
      inhibitor used. Ritonavir and indinavir also showed polarized transport in the
      LLC-PK1 and LLC-PK1:MRP1 cell line, which could be inhibited by probenecid. HIV
      protease inhibitors were not able to inhibit competitively polarized transport of
      other HIV protease inhibitors in the LLC-PK1:MDR1 cell line. CONCLUSIONS:
      Amprenavir, ritonavir and indinavir are mainly actively transported by Pgp, while
      MRP also plays a role in the transport of ritonavir and indinavir. This indicates
      that inhibition of Pgp could be useful therapeutically to increase HIV protease
      inhibitor concentrations in the brain and in other tissues and cells expressing
      Pgp. The HIV protease inhibitors were not able to inhibit Pgp-mediated efflux
      when given simultaneously, suggesting that simultaneous administration of these
      drugs will not increase the concentration of antiretroviral drugs in the brain.

PMID- 11242146
TI  - Therapeutic effects of nucleoside analogues on psychomotor slowing in HIV
      infection.
AB  - OBJECTIVE: Since psychomotor slowing predicts the development of HIV-1-associated
      dementia, AIDS and death independently of the immune status, there is urgent need
      for a neurological therapeutic rationale. METHODS: The therapeutic efficacy of
      nucleoside analogues with different abilities to penetrate into the cerebrospinal
      fluid was assessed in 410 HIV-1-seropositive patients using the results of
      detailed fine motor tests, which detect minor motor deficits. Patients were
      selected who showed pathological psychomotor slowing as signs of central nervous
      system (CNS) dysfunction before therapy onset and who were then treated only with
      nucleoside analogues for at least 6 months. RESULTS: Both zidovudine and
      didanosine improve CNS function to an equal degree when given as monotherapy.
      Adding a second nucleoside analogue (didanosine, lamivudine, zalcitabine) to
      zidovudine does not further improve psychomotor performance. However, adding a
      second nucleoside after a period of zidovudine monotherapy does result in a
      second but less remarkable therapeutic effect. Combinations containing stavudine
      are as effective as those including zidovudine when given as first antiretroviral
      treatment. Furthermore, stavudine effectively improves motor performance even
      after pretreatment with zidovudine.

PMID- 11242147
TI  - Discontinuation of primary prophylaxis in HIV-infected patients at high risk of
      Pneumocystis carinii pneumonia: prospective multicentre study.
AB  - OBJECTIVES: To assess the safety of discontinuation of primary prophylaxis in HIV
      infected patients on antiretroviral combination therapy at high risk of
      developing Pneumocystis carinii pneumonia. DESIGN: Prospective multicentre study.
      PATIENTS AND METHODS: The incidence of P. carinii pneumonia after discontinuation
      of primary prophylaxis was studied in 396 HIV-infected patients on antiretroviral
      combination therapy who experienced an increase in their CD4 cell count to at
      least 200 x 10(6)/l and 14% of total lymphocytes; the study population included
      191 patients with a history of CD4 cell counts below 100 x 10(6)/l (245 person
      years) and 144 patients with plasma HIV RNA above 200 copies/ml (215 person
      years). RESULTS: There was one case of Pneumocystis pneumonia, an incidence of
      0.18 per 100 person-years [95% confidence interval (CI), 0.005--1.0 per 100
      person-years]. No case was diagnosed in groups with low nadir CD4 cell counts
      (95% CI, 0--1.2 per 100 person-years) or detectable plasma HIV RNA (95% CI, 0-
      1.4 per 100 person-years). CONCLUSIONS: Discontinuation of primary prophylaxis
      against Pneumocystis pneumonia is safe in patients who have responded with a
      sustained increase in their CD4 cell count to antiretroviral combination therapy,
      irrespective of the CD4 cell count nadir and the viral load at the time of
      stopping prophylaxis.

PMID- 11242148
TI  - HIV-1 genetic diversity in Galicia Spain: BG intersubtype recombinant viruses
      circulating among injecting drug users.
AB  - BACKGROUND: The HIV-1 epidemics in Western Europe are dominated by B subtype
      viruses. Non-B subtype is largely restricted to individuals infected outside of
      Europe and to their direct contacts and is generally acquired by the heterosexual
      route. METHODS: Protease and a segment of reverse transcriptase were amplified
      and sequenced from plasma RNA in 451 individuals from seven cities of Galicia,
      north-western Spain. Subtype sequence homologies were determined using the BLAST
      algorithm. Non-B sequences were examined by phylogenetic analysis and
      intersubtype recombination by bootscanning. The env V3 region was analysed in all
      non-B and in 38 B subtype viruses. RESULTS: Ten different non-B genetic forms
      were identified in 20 (4.4%) individuals. Subtypes were concordant between pol
      and V3 in five viruses; 14 (70%) infections were with intersubtype recombinant
      viruses, and one individual had a dual B+G infection. Seven recombinant viruses
      were phylogenetically related to five reported recombinant forms. Three non
      recombinant G and six recombinant BG viruses formed a monophyletic cluster for
      pol. All but three individuals with non-B infections were native Spanish. Only 6
      of 16 individuals referred to sexual contacts with sub-Saharan Africans. Twelve
      (60%) non-B subtype infections, including all with G and BG viruses, were in
      injecting drug users (IDU). CONCLUSIONS: Non-B subtype viruses were identified in
      4.4%, with a high diversity of genetic forms, including 70% infections with
      intersubtype recombinant viruses. The majority of individuals with non-B
      infections were IDU, most of them without known contacts with non-European
      sources, and among whom BG recombinant viruses are circulating.

PMID- 11242150
TI  - Rapid dissemination of a novel B/C recombinant HIV-1 among injection drug users
      in southern China.

PMID- 11242149
TI  - Maternal plasma viral load, zidovudine and mother-to-child transmission of HIV-1
      in Africa: DITRAME ANRS 049a trial.
AB  - OBJECTIVE: To study the relationship between maternal plasma RNA levels and
      mother-to-child transmission (MTCT) of HIV-1 in African breastfed children.
      DESIGN: Nested case-control study within a randomized trial assessing the
      efficacy of a short maternal zidovudine (ZDV) regimen to reduce MTCT. METHODS:
      Eligible women received either 300 mg of ZDV twice a day until labour, 600 mg at
      the beginning of labour and 300 mg twice a day for 7 days post-partum or a
      placebo. The diagnosis of paediatric HIV-1 infection was based on PCR tests at
      days 1--8, 45, 90 and 180 then on serology performed at 3 monthl intervals.
      Plasma HIV-1 RNA was measured at inclusion and on day 8 after delivery for all
      women who did transmit HIV to their children (cases) using a Chiron branched DNA
      assay (sensitivity 50 copies/ml) and compared with women who did not transmit
      (two per case) matched for phase trial, treatment allocation and site. RESULTS:
      At inclusion, mean log10 viral load was 4.6 among 55 transmitting mothers and 3.7
      among 117 non transmitters (P = 0.0001). Among transmitters, the mean difference
      in log10 viral load between day 8 post-partum and inclusion was -0.13 in the ZDV
      group (n = 23) versus 0.27 in the placebo group (n = 32; P = 0.01); among non
      transmitters it was -0.35 for the ZDV group (n = 47) versus 0.27 in the placebo
      group (n = 70; P < 10(-4)). In multivariate logistic regression analysis, odds
      ratios for MTCT were 8.7 (95% confidence interval, 3.7-20.6) for 1 log(10)
      increase of maternal RNA at inclusion and 4.2 (95% confidence interval, 1.7-
      10.3) for 1 log(10) increase difference from inclusion to day 8 post-partum.
      CONCLUSION: High maternal viral load at inclusion strongly predicts MTCT of HIV
      in Africa. A short ZDV treatment regimen decreases significantly maternal viral
      load from its pretreatment level.

PMID- 11242151
TI  - Mutations in HIV-1 gag cleavage sites and their association with protease
      mutations.

PMID- 11242152
TI  - Interleukin-16 serum levels during the course of HIV-1 infection.

PMID- 11242153
TI  - Effect of highly active antiretroviral therapy on outcomes in Veterans Affairs
      Medical Centers.

PMID- 11242154
TI  - Mary-Jane and her patients: sociodemographic and clinical characteristics of HIV
      positive individuals using medical marijuana and antiretroviral agents.

PMID- 11242155
TI  - Anal intercourse among young low-income women in California: an overlooked risk
      factor for HIV?

PMID- 11242156
TI  - Peer education has no significant impact on HIV risk behaviours among gay men in
      London.

PMID- 11242157
TI  - Possible hepatitis C virus involvement in acute
      meningoradiculitis/polyradiculitis of HIV-1-co-infected patients.

PMID- 11242159
TI  - Impact of HIV-1 infection on response to treatment of sexually transmitted
      infections.

PMID- 11242158
TI  - Post-exposure prophylaxis affordability: a clearer reality.

PMID- 11242176
TI  - Human antibodies to major histocompatibility complex alloantigens mediate lysis
      and neutralization of HIV-1 primary isolate virions in the presence of
      complement.
AB  - Cellular proteins, including major histocompatibility complex (MHC) class I and
      class II antigens, are incorporated into the membrane of HIV-1 when virions bud
      from infected cells. Experiments were performed to determine whether human sera
      that contained MHC class I and/or class II antibodies would lyse or neutralize a
      primary isolate of HIV. These results demonstrate that in the presence of
      complement, sera from some alloimmunized persons mediated significant anti-viral
      activity against an HIV primary isolate. Both lysis and neutralization of virus
      were observed. The antiviral effects were complement dependent because heat
      inactivation eliminated most anti-viral effects. Antiviral activity mediated by
      sera containing MHC alloantibodies in the presence of complement was > or =
      activity due to sera from HIV-infected persons as reported in this and a previous
      study. High levels of antibodies to both MHC class I and class II were present in
      sera that mediated the highest levels of anti-viral activity. Absorption of serum
      with platelets (which express class I but not class II antigens) substantially
      reduced their lytic activity. These studies suggest that MHC antibodies mediate
      potent anti-viral effects on primary isolates of HIV and support the possibility
      that deliberately alloimmunizing humans might protect against HIV infection.

PMID- 11242177
TI  - In vitro effects of recombinant TNF-alpha binding protein (rTBP-1) on
      hematopoiesis of HIV-infected patients.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is believed to contribute to the
      hematopoietic failure often observed in patients with AIDS. Soluble TNF receptors
      (sTNFR) compete for TNF-alpha with cell surface receptors and thus may block its
      activity. The effect of the p55 sTNFR (recombinant TNF-binding protein-1 [rTBP
      1]) on the clonogenic growth of hematopoietic progenitor cells from 27 HIV
      infected patients was evaluated in comparison with 11 normal study subjects.
      Peripheral blood-derived, myelopoietic (i.e., granulomonocytic colony-forming
      cells [GM-CFC]) and erythropoietic (i.e, burst-forming unit, erythroid [BFU-E])
      colonies were grown in 10-day semisolid cultures with increasing concentrations
      of rTBP-1. Significantly, dose-dependent increases occurred in GM-CFC from 17 of
      21 AIDS patients and 12 of 21 in BFU-E at rTBP-1 concentrations of 1microg/ml to
      25 microg/ml. In contrast, rTBP-1 failed to induce any appreciably increased
      colony formation in normal cell cultures. In 6 patients treated with highly
      active antiretroviral treatment (HAART), TBP-1 alone did not demonstrate the in
      vitro hematopoiesis-enhancing effect. This study may provide an initial step in
      development of therapeutic use of TBP as a TNF-alpha antagonist in HIV-infected
      patients who do not benefit sufficiently from antiretroviral treatment, and in
      other conditions in which increased levels of TNF-alpha may contribute to
      hematopoietic deficiencies.

PMID- 11242178
TI  - Public health consequences of screening patients for adherence to highly active
      antiretroviral therapy.
AB  - Improvements in HIV antiretroviral therapy (ART) have been accompanied by
      increasing recognition of the importance of adherence to treatment regimens for
      maximizing patient benefits while minimizing the emergence of drug-resistant
      virus. Whether clinicians should screen patients for adherence and only
      administer therapy to those believed likely to adhere has not been resolved. We
      first examine the implications of data drawn from a recent study reporting
      physicians' ability to predict whether patients will adhere to highly active
      antiretroviral therapy (HAART) or not. We then extend previously developed
      mathematical models of ART to include screening for adherence and focus on
      resulting drug resistance as well as on HIV and AIDS incidence at the population
      level. We show that although screening for adherence is likely to reduce the
      level of drug resistance compared with a policy of treating all HIV patients with
      HAART, rates of new HIV infections and AIDS cases in the population would likely
      increase unless screening accuracy is extremely (perhaps implausibly) high.

PMID- 11242179
TI  - Primary prevention with cotrimoxazole for HIV-1-infected adults: results of the
      pilot study in Dakar, Senegal.
AB  - OBJECTIVES: To assess the efficacy and tolerance of chemoprophylaxis with
      cotrimoxazole compared with placebo among HIV-1-infected adults. DESIGN:
      Randomized, double-blind, placebo-controlled clinical trial in the urban
      community of Dakar, Senegal. METHODS: Eligibility criteria were age greater than
      15 years, HIV-1 or HIV-1 and HIV-2 dual seropositivity, CD4 cell count lower than
      400 copies/mm3, no progressive infection, no previous history of intolerance to
      sulphonamide, lack of severe anemia or neutropenia, and renal or hepatic failure.
      Written informed consent was obtained. Recruited patients received 80 mg of
      trimethoprim and 400 mg of sulphamethoxazole daily or a matching placebo. The
      main outcomes were survival and the occurrence of clinical events defined as
      Pneumocystis carinii pneumonia, cerebral toxoplasmosis, bacterial pneumonia,
      infectious enteritis, bacterial meningitis, urinary tract infection, bacterial
      otitis and sinusitis, and pyomyositis. RESULTS: Between September 1996 and March
      1998, 297 patients were screened, and 100 were randomized in the study.
      Demographic, clinical, and biological characteristics of the two groups were
      similar as was the mean length of follow-up (7.7 months for the cotrimoxazole
      group vs. 8.0 months for the placebo group). There was no significant difference
      between the two groups in survival (hazard ratio = 0.84; 95% confidence interval
      [CI]: 0.36-1.94) in the probability of severe event occurrence, defined as death
      or hospital admission (hazard ratio = 1.10; 95% CI: 0.57-2.13), or in the
      probability of clinical event occurrence (hazard ratio = 1.19; 95% CI: 0.55
      2.59). Adjustment for initial CD4 cell count did not change these results. A low
      dose of cotrimoxazole was tolerated well clinically as well as biologically; only
      one treatment interruption occurred as the result of a moderate cutaneous
      eruption (grade 2). CONCLUSION: Our study does not show a beneficial effect of
      chemoprophylaxis with low-dose cotrimoxazole on survival or occurrence of
      opportunistic or nonopportunistic infections for HIV-1-infected patients in
      Dakar, Senegal.

PMID- 11242180
TI  - Longitudinal study of anti-Candida albicans mucosal immunity against aspartic
      proteinases in HIV-infected patients.
AB  - Oropharyngeal candidiasis (OPC), mainly caused by Candida albicans, is commonly
      observed in HIV-infected patients. Secreted aspartic proteinases (Saps) are
      virulent agents involved in adherence to the mucosal surface and in tissue
      invasion. The immune secretory response to these agents was investigated in 15
      HIV-infected patients, during oral yeast colonization and episodes of
      oropharyngeal candidiasis (OPC), in a 1-year longitudinal study. We developed an
      avidin-biotin-amplified immunofluorometric assay for the detection of specific
      immunoglobulins G, A, and M against somatic, Sap2 and Sap6 antigens. We report
      increases in anti-somatic, anti-Sap2, and anti-Sap6 salivary antibodies in
      patients with OPC. Over the 1-year period, not only OPC episodes but also
      variations in yeast colonization levels were correlated with variations in
      salivary anti-Sap6 antibody levels. Our results show the ability of HIV-infected
      patients to produce high levels of salivary antibodies; however, these antibodies
      were not efficient in limiting candidal infection, probably because of cellular
      cooperation deficiency and the enhanced virulence of the infecting strain.

PMID- 11242181
TI  - Primary genotypic and phenotypic HIV-1 drug resistance in recent seroconverters
      in Madrid.
AB  - OBJECTIVE: Transmission of drug-resistant HIV-1 strains is increasing with
      widespread use of antiretroviral drugs in developed countries. This study
      examined the prevalence of resistant viruses in recent seroconverters in Madrid,
      Spain. DESIGN: HIV isolates from 30 consecutive participants with positive or
      indeterminate HIV antibody test results and a negative test result at a mean of
      6.6 months earlier were examined for HIV drug resistance. All study subjects
      admitted to having very recently engaged in high-risk practices. All were
      therapeutically naive and were recruited between 1997 and 1999 in a referring
      health care facility for sexually transmitted diseases. METHODS: Population-based
      sequencing of the viral reverse transcriptase (RT) and protease (PR) regions
      derived from plasma viral RNA was performed. Phenotypic resistance was assessed
      by a recombinant virus assay. RESULTS: Overall prevalence of genotypes associated
      with reduced susceptibility was 26.7% (8 of 30 participants). Resistance
      mutations were seen against nucleoside analogues in 7 (23.3%), nonnucleoside
      reverse transcriptase inhibitors in 1 (3.3%), and protease inhibitors in 2
      (6.7%). Zidovudine-resistance mutations M41L and/or T215Y were the commonest,
      found in 20% (6 of 30 participants). Resistance mutations to at least two
      antiretroviral families (multidrug-resistance) were detected in 2 (6.7%) study
      subjects. A median infectious dose (IC50) increase of fourfold for any drug was
      found in 7 patients, and in 2 was > tenfold for zidovudine (genotype M41L +
      T215Y) and lamivudine (genotype M184V), respectively. CONCLUSIONS: Drug-resistant
      HIV variants were present in over one quarter of individuals recently diagnosed
      as infected in Madrid, Spain. Therefore, resistance testing at baseline should be
      considered for the optimal design of first-line antiretroviral combinations.

PMID- 11242182
TI  - Pneumocystis carinii pneumonia recurrence in HIV patients on highly active
      antiretroviral therapy: secondary prophylaxis.
AB  - The incidence and risk factors for Pneumocystis carinii pneumonia (PCP)
      recurrence were evaluated in 451 HIV-infected patients enrolled in the French
      Hospital Database on HIV who started highly active antiretroviral therapy (HAART)
      while receiving secondary PCP prophylaxis after a first episode occurring between
      January 1995 and December 1998. There were 18 episodes of recurrent PCP. On
      HAART, the CD4+ cell count increased to above 200 x 106/L in 274 patients, 51 of
      whom stopped PCP prophylaxis. None of these patients had PCP recurrences during
      363 person-years (PY) of follow-up after the CD4+ cell count had reached 200 x
      106/L (incidence rate [IR], 0.00 cases/100 PY; 95% confidence interval [CI], 0.00
      0.82), and 37 PY of follow-up after the CD4+ cell count had reached 200 x 106/L
      and PCP prophylaxis had been discontinued (IR, 0.00 cases/100 PY; 95% CI, 0.00
      7.84). The CD4+ cell count remained < 200 x 106/L in 177 patients; 9 patients
      stopped PCP prophylaxis, and 6 of these had a disease recurrence. Multivariate
      Cox analysis (time censored when CD4+ cell count > 200 x 106/L) showed that
      discontinuation of secondary prophylaxis (relative hazard [RH], 25.95; p <.0001)
      was associated with recurrence, whereas higher CD4+ cell counts during follow-up
      (RH, 0.39/50 x 106/L increment; p <.002) were protective.

PMID- 11242183
TI  - Gender differences in virologic response to treatment in an HIV-positive
      population: a cohort study.
AB  - OBJECTIVE: To establish whether a gender difference in virologic response to
      highly active antiretroviral treatment (HAART) exists. METHODS: A cohort of HIV
      positive individuals was examined. OUTCOMES: Achievement of viral load <500
      copies/ml and "failure" (failure to suppress viral load <500 copies/ml after 24
      weeks or two consecutive measurements above this level after having suppressed
      below it). Hazard ratios (HRs) comparing the rate in women to that in men were
      derived using the Cox model. RESULTS: Of 366 male subjects, 79% were white and
      82% were homosexual. Sixty-three percent of the 91 female subjects were African
      and 87% were heterosexual. The median follow-up after HAART was 94 weeks. The
      baseline CD4 count was higher in men (228 x 106 per liter) than in women (171 x
      106 per liter) (p =.01), but the viral load was similar (p =.88). The median time
      to <500 copies/ml was 16 weeks. Women achieved a viral load of <500 copies/ml at
      a faster rate than men, with an adjusted HR of 1.46 (95% confidence interval
      [CI]: 0.99-2.16; p =.06). Some 261 patients failed treatment (58% of men and 53%
      of women) with an HR of 0.78 (95% CI: 0.51-1.21; p =.27). CONCLUSIONS: Women may
      achieve virologic suppression at a faster rate than men and have a more durable
      response. Further research should examine these responses in conjunction with
      clinical outcomes, because gender differences in virologic response may
      ultimately be of little relevance if clinical outcomes are similar.

PMID- 11242184
TI  - Trends in HIV seroprevalence and needle sharing among Puerto Rican drug injectors
      in Puerto Rico and New York: 1992-1999.
AB  - This study assessed trends in HIV seroprevalence and needle-sharing behaviors
      among Puerto Rican injection drug users (IDUs) in Puerto Rico and New York. Data
      from two studies of IDUs conducted from 1992 through 1995 and 1998 through 1999
      in Bayamon, Puerto Rico, and East Harlem, New York, were examined to assess
      trends over this period. Separate analyses were conducted for IDUs who were
      current crack smokers. Significant decreasing trends in seroprevalence were found
      among IDUs in the New York and Puerto Rico samples (p <.001). Significant
      decreasing trends in receptive and distributive needle sharing were found in the
      New York sample, and a significant decline in receptive sharing was found in the
      Puerto Rico sample. Overall, higher levels of needle-sharing behaviors were
      reported in Puerto Rico compared with New York. Decreasing trends in needle
      sharing and seroprevalence in both communities are an encouraging finding.
      Ongoing epidemiologic studies to monitor the epidemic and continued prevention
      efforts to help maintain or further these declines are needed, particularly to
      address the higher rates of needle sharing in Puerto Rico.

PMID- 11242185
TI  - Comparison of techniques for HIV-1 RNA detection and quantitation in
      cervicovaginal secretions.
AB  - PRINCIPLES: HIV-1 in female genital secretions has been measured using swabs, Sno
      Strips (Akorn, Inc., Buffalo Grove, IL), and cervicovaginal lavage (CVL), but
      little is known regarding the comparability of these collection techniques.
      METHODS: We compared HIV-1 RNA detection and quantity in specimens obtained from
      HIV-1-seropositive women in Kenya using three sample collection techniques and
      three storage techniques and evaluated reproducibility in samples collected 5
      days apart. Specimens were stored in no medium, freezing medium, or TRI Reagent
      (Molecular Research Center, Cincinnati, OH) for 2 to 15 months. RESULTS: HIV-1
      RNA assays were conducted on 640 specimens from 20 antiretroviral naive women.
      Storage in TRI Reagent significantly enhanced detection of genital HIV-1 and
      yielded significantly higher mean log10 RNA levels than specimens collected in
      either no or freezing medium. The prevalence of HIV-1 RNA detection in TRI
      Reagent ranged from 50% to 80% depending on collection method and was highest in
      cervical swabs. Mean log10 HIV-1 RNA levels were 3.1 log10 copies/cervical swab,
      2.6 log10 copies/cervical Sno Strip, 2.5 log10 copies/vaginal swab, 2.4 log10
      copies/vaginal Sno Strip, 2.9 log10 copies/ml for cervicovaginal lavage (CVL)
      cell pellet, and 2.1 log10 copies/ml in CVL supernatant. Comparing specimens from
      days 1 and 6, there was significant concordance of HIV-1 RNA detection and
      correlation of HIV-1 RNA levels for cervical swabs, vaginal swabs, vaginal Sno
      Strips, and CVL cell pellets (kappa, 0.5-0.9; r, 0.5-0.9), but not for cervical
      Sno Strips or CVL supernatants. CONCLUSIONS: Cervical or vaginal swab, vaginal
      Sno Strip, and CVL collection led to reproducible measurement of genital HIV-1
      RNA, despite storage for several months and international transport. Collection
      using swabs was simpler than Sno Strips or cervicovaginal lavage, and yielded the
      highest prevalence of HIV-1 RNA detection and reproducibility.

PMID- 11242186
TI  - Developing AIDS vaccine trials educational programs in Uganda.
AB  - In preparation for HIV vaccine trials, data on a cohort's knowledge about
      vaccines and vaccine studies are required so as to tailor educational materials
      to adequately meet local needs. Interviews (n = 1,182) conducted as part of a 3
      year prospective study of Ugandan military men aged 18 to 30 years determined
      what information, in addition to standard trials information, would be required
      to ensure comprehension of trial procedures. The interviews highlighted four
      points: (1) the cohort has a lot of knowledge about vaccines but conflates
      whether vaccines cure or prevent disease; (2) there is a general lack of
      knowledge about clinical trials procedures; (3) the desire to be protected from
      HIV/AIDS is a common reason for being willing to participate in a hypothetical
      vaccine trial; and (4) concern about side effects is a common reason for being
      unwilling to participate in a trial. These four points guided the focus of the
      vaccine trials education, which used locally appropriate analogies to introduce
      complex unfamiliar concepts such as placebos and blinding. This case study
      highlights the value of incorporating baseline interviews to assess the
      educational needs of study populations.

PMID- 11242187
TI  - No increased human herpesvirus 8 seroprevalence in patients with HIV-associated
      non-Hodgkin's lymphoma.
AB  - Human herpesvirus 8 (HHV-8) is closely associated with Kaposi's sarcoma (KS), HIV
      associated Castleman's disease, and primary effusion lymphoma. As a high
      frequency of non-Hodgkin's lymphoma (NHL) has been reported in patients with HIV
      associated KS, we hypothesized that HHV-8 infection could be indirectly
      implicated in the pathogenesis of NHL. We assessed the prevalence of HHV-8
      antibodies in 63 patients with NHL compared with 126 HIV-infected matched control
      patients without NHL. Serum samples from cases and controls were assayed for
      antibodies to HHV-8 lytic and latent antigens using an indirect
      immunofluorescence assay. In patients with concordant serologic results, HHV-8
      antibodies were detected in 41.5% of the NHL cases and 37% of the controls. This
      absence of a significant difference in HHV-8 seroprevalence between cases and
      controls (p =.73) does not support a possible role for HHV-8 infection in the
      development of NHL in HIV-infected patients.

PMID- 11242188
TI  - HTLV-1 and HTLV-2 infections in HIV-infected individuals from Santos, Brazil:
      seroprevalence and risk factors.
AB  - Because HTLV-I, HTLV-2, and HIV share identical modes of transmission,
      simultaneous or subsequent infections with these retroviruses are to be expected.
      The population of Santos, the largest port in Latin America, includes large
      numbers of female commercial sex workers and intravenous drug users, presumably
      having been exposed to retroviral infection. To evaluate the seroprevalence of
      HTLV infection and their associated risk factors, a cross-sectional survey was
      carried out in 499 HIV-infected individuals from Santos, Brazil. HTLV testing
      consisted of enzyme immunoassays for serologic screening and confirmatory Western
      blot testing. Overall HTLV-I and HTLV-2 seroprevalences were 6.0% (95% confidence
      interval [CI], 3.9-8.1) and 7.4% (95% CI, 5.1-9.7), respectively. Multivariate
      logistic regression for statistical analysis revealed HTLV-I infection to be
      independently associated with: intravenous drug use (IDU) (odds ratio [OR]. 2.99;
      95% CI, 1.09-8.20), seropositivity to hepatitis C virus (HCV) (OR, 3.03; 95% CI,
      1.02-9.01) and < 3 years of education (OR, 4.73; 95% CI, 1.56-14.41). HTLV-2
      infection was associated with: IDU (OR, 3.22; 95% CI, 1.33-7.84), HCV
      seropositivity (OR, 5.40; 95% CI, 1.86-15.66) and nonwhite race (OR, 3.32; 95%
      CI, 1.58-7.00). Results indicate that HIV-infected individuals living in Santos
      are at similarly high risk of being exposed to HTLV-1 and HTLV-2. IDU constitutes
      the main risk factor for HTLV acquisition in this population, and there is no
      significant risk associated with sexual practice.

PMID- 11242189
TI  - Reasons for discontinuation of first highly active antiretroviral therapy in a
      cohort of proteinase inhibitor-naive HIV-infected patients.

PMID- 11242190
TI  - Comparative assessment of five alternative methods for CD4+ T-lymphocyte
      enumeration for implementation in developing countries.

PMID- 11242191
TI  - Dissociation of responses to highly active antiretroviral therapy:
      Notwithstanding virologic failure and virus drug resistance, both CD4+ and CD8+ T
      lymphocytes recover in HIV-1 perinatally infected children.

PMID- 11242192
TI  - Evidence of productively infected CD8+ T cells in patients with AIDS:
      implications for HIV-1 pathogenesis.
AB  - CD8+ T lymphocytes play an important protective role against HIV infection. The
      onset of AIDS is associated with a decline in both the number of CD8+ T
      lymphocytes and anti-HIV cytotoxic activity in CD8+ T cells. The reason for this
      progressive failure of CD8+ T cells in HIV-1 infection remains unknown. Earlier
      reports have shown presence of viral DNA in CD8+ cells of HIV-1-infected
      patients; under some conditions, CD8+ T cells have been shown to express CD4 in
      vitro and can be susceptible to infection with HIV-1. However, whether CD8+
      lymphocytes in vivo can be productively infected with HIV-1 remains unclear. In
      this study, we generated multiple CD8+ T-cell clones from two patients with AIDS.
      These clones were CD8+/CD3+ but did not express CD4. Several of these CD8+ clones
      from both patients were found to be endogenously infected with HIV-1 and
      spontaneously produced these viruses. CD8+ cell-produced HIV-1 was biologically
      competent because viruses produced by most of these clones could efficiently
      infect and replicate in peripheral blood lymphocytes from HIV-negative donors. In
      addition, some of these viruses were able to form syncytia in MT-2 cells
      indicating syncytium-inducing phenotype. Comparison of the sequences in V3 loop
      areas among different viruses showed changes in some of the clones from both
      patients. For the first time, this report provides direct evidence that mature
      CD8+ T cells can be productively infected with HIV-1 in patients with AIDS.
      Direct infection of CD8+ T lymphocytes may play a role in the eventual failure of
      these cells in HIV-1 infection.

PMID- 11242193
TI  - Effect of HIV-1 infection on lymphocyte proliferation in gut-associated lymphoid
      tissue.
AB  - OBJECTIVE: To determine the change in the percentage of proliferative and
      activated lymphocytes in gut-associated lymphoid tissue (GALT) in HIV-1-infected
      subjects compared with that in uninfected controls. METHODS: We measured the
      percentage of proliferative (Ki-67+) and activated (CD-69+, HLA-DR+, CD45RO+)
      lymphocytes from GALT and peripheral blood in chronically HIV-1-infected (12) and
      uninfected (9) individuals. RESULTS: The percentage of proliferative GALT CD4+ T
      cells was increased in HIV-1-infected control subjects compared with that in
      uninfected controls (p <.007). Based on immunohistochemical staining,
      proliferative T cells were principally located in the parafollicular area
      surrounding lymphoid aggregates. The percentage of activated GALT lymphocytes,
      however, was not significantly different in HIV-1-infected individuals, whereas
      it was significantly increased in the peripheral blood of HIV-1-infected
      individuals. The percentage of peripheral blood lymphocytes trafficking to the
      intestine was also not significantly different in HIV-1-infected individuals
      compared with that in uninfected controls. CONCLUSIONS: CD4+ T cell proliferation
      in GALT is increased in HIV-1 infection without a significant alteration in the
      percentage of peripheral blood T cells trafficking to the gastrointestinal
      mucosa.

PMID- 11242194
TI  - A retrospective, cohort-based survey of patients using twice-daily indinavir +
      ritonavir combinations: pharmacokinetics, safety, and efficacy.
AB  - OBJECTIVE: To describe the pharmacokinetics, safety, and efficacy of twice-daily
      indinavir + ritonavir regimens DESIGN: A cohort-based survey of HIV-infected
      patients who either used indinavir 800 mg + ritonavir 100 mg twice daily or
      indinavir 400 mg + ritonavir 400 mg twice daily. METHODS: Data were extracted
      from a database of samples sent to our laboratory for measurement of indinavir +
      ritonavir plasma concentrations. Patient characteristics, safety, and efficacy
      measurements were collected by retrospective chart review. RESULTS: 100 Patients
      using 800-mg indinavir + 100-mg ritonavir twice daily and 32 patients using 400
      mg indinavir + 400-mg ritonavir twice daily were eligible. Median peak and trough
      concentrations of indinavir were 6.8 and 0.77 mg/L in the 800/100 group and 2.6
      and 0.45 mg/L in the 400/400 group. The most frequently found side effects were
      nausea and vomiting, which occurred in 22.1% and 34.9% of the patients in the
      800/100 and the 400/400 groups, respectively. Viral load data were analyzed for
      patients who switched from 800-mg indinavir three times daily to one of the
      indinavir + ritonavir twice daily regimens. At the time of switch 63% (800/100
      group) and 60% (400/400 group) had an undetectable viral load and this increased
      to 77% and 70%, respectively, during follow-up. Patients who switched to the
      400/400 group discontinued treatment more frequently than patients who switched
      to the 800/100 group (70% vs. 26%, p =.008). CONCLUSIONS: Indinavir + ritonavir
      regimens show improved pharmacokinetic properties, allowing twice-daily dosing
      with food. Clinical data suggest that safety and efficacy is at least as good as
      with indinavir three-times-daily regimens without ritonavir. Prospective,
      comparative trials are needed to properly assess the role in HIV therapy of these
      twice-daily indinavir + ritonavir regimens.

PMID- 11242195
TI  - Alterations of apolipoprotein B metabolism in HIV-infected patients with
      antiretroviral combination therapy.
AB  - BACKGROUND: Dyslipidemia (predominantly hypertriglyceridemia) is frequently seen
      in patients receiving antiretroviral combination therapy (ART). However, the
      underlying mechanisms and long-term risks (e.g., cardiovascular events) are still
      unclear. OBJECTIVES/METHODS: In 5 patients with ART-associated dyslipidemia,
      stable isotope labeled amino acid tracer (d3-Leu) kinetic analysis over 12 days
      was used to investigate the metabolism of apolipoprotein B-containing
      lipoproteins (very low density lipoproteins [VLDL]1, VLDL2, intermediate density
      lipoproteins [IDL] and low density lipoproteins [LDL]). Data were compared with
      those in 6 healthy normolipidemic controls. RESULTS: The patients under ART
      showed significantly increased fasting triglycerides (359 vs. 77 mg/dl) and VLDL
      (54 vs. 15 mg/dl), compared with controls. They had significantly higher total
      cholesterol (213 vs. 157 mg/dl) and there was a nonsignificant trend toward
      higher LDL (136 vs. 93 mg/dl), and toward lower HDL (26 vs. 46 mg/dl). The ratio
      of large, buoyant LDL1 over small, dense LDL2 was markedly reduced in patients
      under ART (0.80 vs. 2.00). Total apo B synthesis was significantly increased
      (25.5 vs. 14.5 mg/kg/d) and shifted toward triglyceride rich VLDL1 (18.5 vs. 8.7
      mg/kg/d) in patients receiving ART. There was also a significantly reduced rate
      of apo B lipoprotein transfer from VLDL1 to VLDL2 (3.7 vs. 20.7 pools/d). In
      addition, all patients revealed insulin resistance. CONCLUSIONS: These data
      indicate that increased triglycerides in HIV-infected patients with ART are
      primary due to reduced rates of VLDL transfer into denser lipoproteins implying a
      lower rate of lipoprotein lipase-mediated delipidation. In addition, total apo B
      synthesis was increased and shifted toward triglyceride-rich VLDL1. Overall, this
      lipoprotein profile in patients with ART-associated dyslipidemia implies an
      increased risk for cardiovascular events.

PMID- 11242196
TI  - Mode of delivery and postpartum morbidity among HIV-infected women: the women and
      infants transmission study.
AB  - Cesarean delivery before onset of labor and rupture of membranes (i.e., scheduled
      cesarean delivery) is associated with a lower risk of vertical transmission of
      HIV. The following a priori hypotheses were tested: among HIV-infected women,
      scheduled cesarean delivery is associated with a higher risk of postpartum
      morbidity, longer hospitalization, and a higher risk of rehospitalization than
      spontaneous vaginal delivery. Postpartum morbidity occurred following 178 of
      1,186 (15%) of deliveries during 1990 to 1998 in The Women and Infants
      Transmission Study. The most commonly reported postpartum morbidity events were:
      fever without infection, hemorrhage or severe anemia, endometritis, urinary tract
      infection, and cesarean wound complications. Several time trends were observed:
      the median duration of ruptured membranes decreased (p < .001), intrapartum
      antibiotic use increased (p < .001), the median antepartum plasma HIV RNA
      concentration decreased (p < .001), and the incidence of any postpartum morbidity
      decreased (p = .02). With spontaneous vaginal delivery as the reference category,
      both scheduled (odds ratio [OR] = 4.69; 95% confidence interval [95% CI], 2.03
      10.84), and nonscheduled (OR, 2.50; 95% CI, 1.24-5.04) cesarean deliveries were
      associated with fever without infection; with urinary tract infection (OR, 3.79;
      95% CI 1.04-13.85; OR, 3.86; 95% CI, 1.55-9.60, respectively), and with any
      postpartum morbidity (OR, 3.19; 95% CI 1.69-6.00; OR, 4.10; 95% CI, 2.71-6.19,
      respectively). Nonscheduled cesarean deliveries were more likely to be
      complicated by endometritis (OR, 6.98; 95% CI, 3.53-13.78). Adjusted ORs relating
      mode of delivery and each of the outcomes (fever without infection, urinary tract
      infection, endometritis, and any postpartum morbidity) were similar to unadjusted
      ORs. Results of this analysis indicate scheduled cesarean delivery is associated
      with an increased risk of any postpartum morbidity and, specifically, postpartum
      fever without infection. The potential for postpartum morbidity with scheduled
      cesarean delivery should be considered in light of possible adverse events
      associated with other interventions to decrease the risk of vertical transmission
      of HIV. Counseling of HIV-infected pregnant women regarding scheduled cesarean
      delivery as a possible intervention to decrease maternal-infant transmission of
      HIV should include discussion of these results, as well as new data as they
      become available, regarding the incidence and severity of postpartum morbidity
      events among HIV-infected women according to mode of delivery.

PMID- 11242197
TI  - Analyses of nursing home residents with HIV and dementia using the minimum data
      set.
AB  - OBJECTIVE: The objective of this paper is to profile nursing home residents with
      HIV who also have dementia at the time of admission, using the Minimum Data Set
      (MDS). In addition, this paper compares HIV residents with dementia with other
      residents with HIV. These resident profiles contain sociodemographic
      characteristics, health status measures, treatments, and procedures. STUDY
      SUBJECTS: There are 1,074 admission assessments for HIV residents with dementia
      and 4,040 admission assessments for other residents with HIV in the MDS between
      June 22, 1998 and January 17, 2000; these were analyzed for this study. RESULTS:
      Other residents with HIV were twice as likely to be physically independent as HIV
      residents with dementia. Only 1 of 5 HIV residents with dementia was independent
      in cognitive skills for daily decision making compared with 3 of 5 other
      residents with HIV who were independent in these skills. Significantly greater
      percentages of HIV residents with dementia also had anemia, depression,
      schizophrenia, cognitive and memory problems, hepatitis, renal failure, and
      cancer than other residents with HIV. CONCLUSIONS: These analyses demonstrate
      that HIV residents with dementia were significantly more likely to have other
      diseases, infections, and health care conditions than other residents with HIV.

PMID- 11242198
TI  - Detection of genetic changes in anal intraepithelial neoplasia (AIN) of HIV
      positive and HIV-negative men.
AB  - Compared with HIV-negative individuals, HIV-positive individuals have a higher
      prevalence of anogenital human papillomavirus (HPV) infection, as well as a
      higher incidence of HPV-associated anal cancer. Little is currently known of
      chromosomal changes occurring in anal intraepithelial neoplasia (AIN), the
      probable precursor to anal cancer. Genetic changes in AIN were characterized by
      comparative genomic hybridization (CGH) in a study of samples obtained from 19
      HIV-positive and 11 HIV-negative men. The proportion with genetic changes
      significantly increased with the severity of the histopathologic grade with none
      diagnosed as (0%) AIN 1; 5 of 17 (29%) as AIN 2; and 5 of 9 (56%) AIN 3 showing
      genetic changes (p = .02). This correlation was also found in study subjects who
      had multiple biopsies with different grades of pathology concurrently or serially
      over time. The most common regional DNA copy number change was gain mapped to
      chromosome arm 3q (12% of AIN 2 and 33% of AIN 3). This alteration was previously
      reported to be commonest alteration in cervical cancer, which suggests a common
      molecular pathway for these two HPV-associated anogenital neoplasias.

PMID- 11242199
TI  - Survey of nonoccupational HIV postexposure prophylaxis in hospital emergency
      departments.
AB  - BACKGROUND: Nonoccupational HIV postexposure prophylaxis (nPEP) is being used in
      community settings, but little is known about practice patterns. This study
      examined the status of nPEP in Massachusetts emergency departments (EDs),
      community sites where nPEP is most likely to be practiced. METHODS: In June 1998,
      a mailed survey was sent to identified medical directors of the 78 hospital EDs
      statewide; 66 (85%) responded. RESULTS: Overall, 52% reported having patient
      requests for nPEP within the prior year. 15% (10 of 66) had established written
      nPEP protocols; 33% (22 of 66) indicated their protocols were informal and not
      written. Twenty-five EDs could estimate the number of nPEP patients assessed;
      their mean estimate was 31 for the prior year (standard deviation [SD], 19.9) and
      34% of the patients overall had nPEP recommended. Most (81%) of the hospitals
      with written or unwritten protocols recommended the use of three-drug
      antiretroviral regimens, which included two nucleoside analogues and a protease
      inhibitor; 41% approved more than one nPEP regimen. CONCLUSIONS: A demand for
      nPEP is occurring in hospital EDs. The diversity of practice patterns suggests
      the need for evidence-based practice guidelines.

PMID- 11242200
TI  - Frequency of genotypic and phenotypic drug-resistant HIV-1 among therapy-naive
      patients of the German Seroconverter Study.
AB  - Genotypic and phenotypic resistance of viral reverse transcriptase (RT) and
      protease (PR) was determined for 64 therapy-naive, HIV-1-infected seroconverters
      of the German Seroconverter Study coordinated by the Robert Koch-Institut,
      Berlin. The date of seroconversion of patients and the laboratory, clinical, and
      therapeutic follow-up data were documented. Samples were collected between 1996
      and 1999. Phenotypic resistant HIV-1 were found in 8 (13%) seroconverters; in
      most cases resistance was weak and mainly directed against RT inhibitors (4
      nucleoside reverse transcriptase inhibitors [NRTIs], 2 nonnucleoside reverse
      transcriptase inhibitors [NNRTIs], 1 combination NRTI/NNRTI). Only one infection
      with a weak PR inhibitor resistance was identified. Transmission of multidrug
      resistant HIV-1 has not yet been observed. Frequently at least one or more amino
      acid mutations associated with antiretroviral drug resistance were detected by
      genotypic analysis. The mean number of resistance-associated mutations in the RT
      of the transmitted virus has increased significantly since 1996. Studies have
      shown the improved benefit of initial antiretroviral therapy if based on
      genotypic resistance data. In view of the considerably high level of transmission
      of resistant HIV-1 in Germany, which is also seen in other studies in Europe and
      the United States, we suggest determining the genotypic resistance pattern before
      starting therapy of newly HIV-1-infected patients.

PMID- 11242201
TI  - Temporal trends and molecular epidemiology of HIV-1 infection in Taiwan from 1988
      to 1998.
AB  - Eight hundred and seventy-nine HIV-1-infected patients (comprising 46% of
      reported HIV-1/AIDS cases in Taiwan) were recruited for this study of the
      molecular epidemiology of HIV-1 in Taiwan from 1988 to 1998. HIV-1 subtypes were
      determined using a modified peptide-enzyme immunoassay complemented with DNA
      sequencing and phylogenetic analysis. Of the 807 HIV-1 infected men, 68.2% were
      infected with HIV-1B, 29.5% with HIV-1 circulating recombinant form (CRF)01_AE
      and 2.3% with other subtypes. Of the 72 HIV-1-infected women, 72.2% were infected
      with HIV-1 CRF01_AE, 13.9% with HIV-1B, and 13.9% with other subtypes. All of 8
      foreign-born, Southeast Asian women and 6 of 7 (85.7%) Taiwan-native female
      commercial sex workers were infected with HIV-1 CRF01_AE. Fourteen of the 33
      (42.4%) heterosexual married men with CRF01_AE had transmitted HIV-1 to their
      wives, whereas only 1 of 17 (5.9%) men with HIV-1 B had transmitted HIV-1 to
      their spouses (p < .01). Of 18 heterosexual male injecting drug users, 1 of 12
      (8.5%) with HIV-1B and 5 of 6 (83.3%) with HIV-1 CRF01_AE had had sexual contact
      with female commercial sex workers (p < .01). Therefore, in this population,
      CRF01_AE was preferentially associated with heterosexual risk groups, a finding
      compatible with differences in transmission capability between B and non-B
      subtypes.

PMID- 11242202
TI  - Spectrum of AIDS-defining illnesses in Australia, 1992 to 1998: influence of
      country/region of birth.
AB  - OBJECTIVE: To examine the influence of country/region of birth on spectrum of
      AIDS-defining illness. METHODS: National surveillance data for 4,629 adolescents
      and adults diagnosed with AIDS from 1992 through 1998 were analyzed. Country of
      birth was grouped into five broad categories (Australia, other predominantly
      industrialized country regions, sub-Saharan Africa, Asia-Pacific, and other
      regions with predominantly developing countries). Proportions of AIDS-defining
      illnesses were calculated and compared by country/region of birth. Role of
      country/region of birth in the distribution of AIDS-defining illnesses was
      further assessed using logistic models. RESULTS: Of the 4,488 (97.0%) AIDS cases
      with country of birth recorded, 1,120 (25.0%) were born outside Australia. In
      multivariate analyzes, AIDS cases born in sub-Saharan Africa had an increased
      risk of tuberculosis (odds ratio [OR], 18.7; confidence interval [CI], 9.2-38.2)
      and cryptococcosis (OR, 2.4; CI, 1.1-5.4), but a decreased risk of esophageal
      candidiasis (OR, 0.3; 0.1-0.8) and Pneumocystis carinii pneumonia (OR, 0.5; 0.3
      0.9) compared with AIDS cases born in Australia. Tuberculosis risk was also
      elevated among AIDS cases born in Asia-Pacific (OR, 9.6; 5.3-17.5) and other
      developing country regions (OR, 3.1; 0.9-10.4). Risk of AIDS-defining illnesses
      was similar for AIDS patients born in Australia and other industrialized country
      regions. Country of birth had no influence on risk of cytomegalovirus (CMV)
      related disease and Mycobacterium avium complex (MAC) infection. Differential
      AIDS-defining illness risk was more pronounced among AIDS patients born in
      developing countries who had resided in Australia for less time. CONCLUSIONS:
      Differential risk by country/region of birth for some AIDS-defining illnesses,
      especially among more recent arrivals from developing countries, suggests that
      environmental microbial habitats are important determinants of opportunistic
      infection risk. Similar risk of CMV disease and MAC infection is consistent with
      the ubiquitous nature of these microbial agents and suggests that previously
      reported low prevalence from developing countries may reflect poor diagnostic
      capacity rather than level of risk.

PMID- 11242203
TI  - Prevalence and predictive value of overweight in an urban HIV care clinic.
AB  - OBJECTIVE: To determine the prevalence and predictive value of overweight in an
      urban HIV clinic. METHODS: Medical records of all new adult, nonpregnant
      registrants in 1996 in an urban HIV clinic with at least one height and weight
      measurement were reviewed. Body mass index (BMI) at clinic enrollment was
      calculated, and prevalence of overweight was thus determined. The subsequent
      clinical course of the overweight group was compared with that of a randomly
      selected group of gender-stratified non-overweight patients. RESULTS: At
      baseline, 12.6% of men and 32.5% of women were overweight. Female gender and lack
      of AIDS diagnosis were independently associated with overweight. More than one
      half of women and 19.6% of men were overweight at some point during the study.
      Providers were more likely to properly acknowledge underweight than overweight.
      Among patients without AIDS, there was a trend toward slower disease progression
      and lower viral load in overweight patients, despite similar baseline CD4+
      lymphocyte counts and similar time to initiation of highly active antiretroviral
      therapy. In multivariate proportional hazards analyses, lower baseline BMI and
      falling BMI during follow-up were independently predictive of progression to
      AIDS. CONCLUSIONS: Overweight was a common and underrecognized finding,
      particularly among women. Overweight patients may progress more slowly to AIDS
      than non-overweight patients.

PMID- 11242204
TI  - Contrasting frequencies of CCR5delta32 and CCR2-64I alleles in the Tunisian
      population.

PMID- 11242205
TI  - Chronic hepatitis C in HIV-coinfected patients: feasibility and efficacy of
      interferon-alpha2b and ribavirin combination therapy.

PMID- 11242206
TI  - Experimental results on chloroquine and AIDS-related opportunistic infections.

PMID- 11242207
TI  - MR evaluation of factors predicting the development of rotator cuff tears.
AB  - PURPOSE: The purpose of this work was to assess the incidence of various factors
      predicting impingement in the shoulder. METHOD: MR examination was used to assess
      various anatomic parameters in 46 patients with clinical abnormalities of the
      shoulder and 40 asymptomatic volunteers. All patients had undergone surgery,
      showing no rotator cuff tear. RESULTS: A few of the parameters evaluated were
      significantly different in the two groups: The acromion was more frequently
      curved or hook-shaped in patients than in volunteers. The acromiohumeral
      distances differed (4.87 mm in patients and 6.05 mm in volunteers); so did the
      coracohumeral distances (7.9 mm in patients and 8.9 mm in volunteers). The shape
      of the acromioclavicular joint and the anterior covering of the humerus, defined
      on the coronal view, also differed (1.07 mm in patients and 1.49 mm in
      volunteers). Only the shapes of the acromioclavicular joint and of the acromion
      were linked with age. CONCLUSION: All these factors reflected a decrease in the
      acromiohumeral space, except for the anterior covering of the acromial arch,
      which could be due to anterior instability.

PMID- 11242208
TI  - Spinal fractures and pseudoarthrosis complicating ankylosing spondylitis: MRI
      manifestation and clinical significance.
AB  - PURPOSE: To analyze magnetic resonance (MR) patterns of fractures and
      pseudoarthrosis of the ankylosing spondylitic spine, and related changes in the
      dura and adjacent soft tissue. MATERIALS AND METHODS: Sixteen patients with
      radiographically evident fractures or pseudoarthrosis of the spine were included.
      Each underwent MR studies. Ten patients among them underwent surgical operations.
      RESULTS: Both transdiscal (n = 12) and transvertebral (n = 4) fractures were
      identified. The levels were located from T9 to L3. Five of 16 patients had
      pseudoarthrosis. The fractures or pseudoarthrosis had two patterns: low signal on
      T1-and high signal on T2-weighted images, and low signal on both T1-and T2
      weighted images. Disruption of anterior longitudinal ligament (ALL) was
      identified in 14 patients. Seven patients had vertebral translation, all had
      disruption of the ALL. Dural adhesions were noted in five patients and manifested
      as linear epidural enhancements with triangular blunt edges. CONCLUSION: MR
      patterns of ankylosing spondylitis are important in evaluating complications of
      fractures or pseudoarthrosis, as well as changes in dura, soft tissue, and
      ligaments.

PMID- 11242209
TI  - Craniovertebral junction tuberculosis: a review of 29 cases.
AB  - PURPOSE: The purpose of this work was to describe the various imaging findings in
      craniovertebral tuberculosis and the importance of imaging in treatment in these
      patients. METHOD: A retrospective review of MR and CT scans in 29 patients with
      craniovertebral tuberculosis was performed. The images were reviewed, paying
      special attention to both bony (skull base, atlas, and axis) and soft tissue
      involvement in addition to atlantoaxial dislocation, lateral subluxation of the
      dens, and compression of the spinal cord. RESULTS: Suboccipital pain with neck
      stiffness was the most common presenting symptom in our patients. The skull was
      involved in 19 of the 29 cases, clivus involvement was seen in 11 patients, and
      occipital condyle involvement was present in 14 patients. Detailed analysis of
      atlas involvement due to tuberculosis showed the lateral masses to be
      predominantly affected. The dens was involved in 18 cases (62%). Soft tissue
      masses in the prevertebral area were seen in 22 patients, paravertebral in 27
      patients, and epidural involvement in 25 patients was identified. Atlantoaxial
      displacement was present in seven cases, lateral mass-dens subluxation in five,
      and superior subluxation of the dens through the foramen magnum compressing the
      medulla was seen in two cases. Spinal cord compression with intrinsic cord
      changes was noted in 12 cases. All patients received multidrug antituberculous
      therapy for 1 year. The presence of neurologic deficit and instability of the
      atlantoaxial complex was pivotal in further management in these patients.
      CONCLUSION: A high degree of clinical suspicion is necessary when confronted with
      patients with neck stiffness and tenderness over the upper cervical vertebrae.
      MRI in these patients provides a sensitive method for the diagnosis of
      craniovertebral tuberculosis.

PMID- 11242210
TI  - MRI of musculoskeletal extraspinal tuberculosis.
AB  - PURPOSE: The aim of this study was to describe the MR findings in extraspinal
      musculoskeletal tuberculosis (EMT). METHOD: A retrospective review was conducted
      of the MR findings of 18 patients with microbiologically and/or pathologically
      proven EMT. All MR studies were performed using T1-and T2-weighted spin echo
      sequences. T1-weighted spin echo sequences after Gd-DTPA injection were obtained
      for 12 patients. The MR images were evaluated for abnormalities in joints, bones,
      and soft tissues, and the results were grouped by anatomic localization,
      frequency distribution of structures affected, and morphologic patterns of
      involvement. RESULTS: Isolated soft tissue tuberculosis was found in 10 (55.5%)
      patients and involvement of more than one structure in 8 (44.4%). Pyomyositis (n
      = 6) and arthritis with involvement of adjacent soft tissues (n = 7) were the
      most common forms of presentation. One patient presented with isolated fascial
      superficial tissue involvement in one leg. Isolated pyomyositis involving one (n
      = 3) or two (n = 3) muscles was homogeneous in six cases and showed intermediate
      (n = 6), low (n = 2), or high (n = 1) signal intensity on T1-weighted images and
      a high and very hyperintense signal on T2-weighted images. The tenosynovitis
      synovial fluid was homogeneous (n = 1) or heterogeneous with multiple tiny
      hypointense nodules (n = 1) on T2-weighted images. The subdeltoid bursitis fluid
      was characterized by homogeneous low signal intensity with a hyperintense rim (n
      = 2) on T1-weighted images and homogeneous (n = 1) or heterogeneous hyperintense
      signals with areas of low signal intensity (n = 1) on T2-weighted images. In
      tuberculous arthritis, the synovial joint fluid (n = 7) showed heterogeneous (n =
      4) or homogeneous (n = 3) low signal intensity on T1-weighted images and high or
      very high signal intensity on T2-weighted images. Where involved, the adjacent
      muscle(s) (n = 8) were usually hypointense on T1-weighted images and very
      hyperintense on T2-weighted images. Associated cellulitis was found in arthritis
      with involvement of neighboring soft tissues (n = 5), pyomyositis (n = 2), and
      tenosynovitis (n = 1). The images obtained after Gd-DTPA showed peripheral (n =
      10) or heterogeneous (n = 1) enhancement or no enhancement (n = 1). CONCLUSION:
      The MR findings for EMT are variable. Although diagnosis is dependent largely on
      prior presumption and clinical context, MRI provides valuable guidelines in
      defining the extent of the lesions to select the appropriate treatment and for
      follow-up of abnormalities.

PMID- 11242211
TI  - Coincidence camera FDG imaging for the diagnosis of chronic orthopedic
      infections: a feasibility study.
AB  - PURPOSE: Results of dedicated [(18)F]fluoro-2-deoxy-d-glucose (FDG) PET imaging
      in patients with suspected orthopedic infections are promising. This study
      evaluates the feasibility of dual-head gamma-camera coincidence (DHC) imaging in
      this population. METHOD: Twenty-four patients, referred for the confirmation or
      exclusion of orthopedic infection, were prospectively studied with consecutive
      FDG-dedicated PET and FDG DHC imaging. Images were read by two blinded readers
      experienced with FDG PET and compared with the final diagnosis, obtained by
      microbiologic proof in 11 patients and clinical follow-up of at least 9 months in
      13 patients. RESULTS: Nine patients had osseous infection on final diagnosis.
      Sensitivity, specificity, and accuracy in this limited series were (Reader
      1/Reader 2), respectively, 100/100, 86/86, and 92/92% for FDG-dedicated PET and
      89/89, 100/93, and 96/92% for FDG DHC imaging. CONCLUSION: Despite lower image
      quality for FDG DHC imaging, results in this limited series were comparable with
      the results of FDG-dedicated PET. Further studies are needed to confirm the
      utility of FDG DHC imaging in suspected chronic orthopedic infections in larger
      patient groups.

PMID- 11242212
TI  - Fast MRI in obstetric diagnoses.
AB  - This article describes the fast MRI of fetal abnormalities and placental
      anomalies in evaluation of the usefulness of fast MRI in obstetric diagnoses.
      Fast MRI provides excellent resolution for imaging fetal and maternal anatomies
      without the need for sedation. Fast MRI is therefore useful to clarify diagnoses
      suggested by equivocal ultrasonographic findings and to obtain additional
      information for prenatal counseling and management.

PMID- 11242213
TI  - Sclerosing stromal tumor of the ovary: US, MR, and dynamic MR findings.
AB  - The US, MR, and dynamic MR findings in four patients with sclerosing stromal
      tumor of the ovary are reported. US showed a tumor with multilocular cystic
      components and irregularly thickened septa and tumor walls or a solid tumor
      including several small cystic components. On T2-weighted MR images, signal
      intensities of the cystic components were high and those of the solid components
      were inhomogeneous, ranging from intermediate-high to high. Dynamic MRI
      demonstrated marked early enhancement of the solid components.

PMID- 11242214
TI  - Castleman disease of the abdomen: imaging spectrum and clinicopathologic
      correlations.
AB  - PURPOSE: The purpose of this work was to define the imaging spectrum of Castleman
      disease of the abdomen and to correlate the results with clinicopathologic
      findings. METHOD: Seventeen patients (male/female 7:10; mean age 35.6 years) with
      pathologically proved Castleman disease in the abdomen were included in this
      study. Radiologic findings (CT, n =17; US, n =10; MR, n =1) were retrospectively
      reviewed by two readers and were correlated with clinical and pathologic
      findings. RESULTS: Subjects were divided into those with localized (n = 11) and
      disseminated (n = 6) disease. In localized disease, the pathologic subtypes were
      hyaline vascular type in eight and plasma cell type in three. Radiologic studies
      showed a single large mass in six and a single dominant mass with small satellite
      nodules in five. Central low attenuation was seen in two cases, and calcification
      was seen in three cases. Regional lymphadenopathy was found in five cases. In
      disseminated disease, there were three hyaline vascular types and three plasma
      cell types. Radiologic findings included diffuse lymphadenopathy (n = 6),
      hepatosplenomegaly (n = 5), ascites (n = 3), and thickening of the
      retroperitoneal fascia (n = 3). Disseminated disease revealed symptoms and
      abnormal laboratory findings (anemia, hypoalbuminemia, elevated erythrocyte
      sedimentation rate/C-reactive protein, etc.) more frequently than localized
      disease and showed poor prognosis. CONCLUSION: There are two distinctive types of
      radiologic manifestations in Castleman disease of the abdomen: localized and
      disseminated. The localized type usually shows single or multiple discrete
      masses, and the disseminated type frequently shows nonspecific organomegaly and
      lymphadenopathy.

PMID- 11242215
TI  - Severe spontaneous ovarian hyperstimulation syndrome with MR findings.
AB  - We describe a case of severe spontaneous ovarian hyperstimulation syndrome (OHSS)
      with MR findings. MR scans showed bilateral symmetric enlargement of ovaries with
      multiple cystic changes, giving the classic "wheel-spoke" appearance. There was
      no definite abnormally thickened or enhanced wall, but there was internal
      hemorrhage in some chambers. To avoid unnecessary laparotomy, we emphasize the
      importance of careful diagnosis to differentiate spontaneous OHSS from ovarian
      cystic neoplasms.

PMID- 11242216
TI  - Opacification of the intrahepatic portal veins during CT hepatic arteriography.
AB  - PURPOSE: The purpose of this study was to ascertain the cause of opacification of
      the portal veins during CT hepatic arteriography (CTHA). METHOD: A total of 155
      consecutive patients with hepatocellular carcinoma were evaluated with CTHA as
      preoperative staging. The opacification of the portal veins during CTHA was
      categorized as opacification of the main portal vein, right or left branches of
      the main portal vein (generalized), and segmental or subsegmental portal veins
      (localized). Hepatic angiography was compared and possible causes were evaluated.
      RESULTS: One hundred eight (70%) of 155 patients showed intrahepatic portal vein
      opacification at CTHA: generalized in 60 patients (39%) and localized in 48
      patients (31%). Intrahepatic causes were arterioportal shunts due to
      hepatocellular carcinoma in 20 (19% of 108 patients), previous liver biopsy in 9
      (8%), and portal vein thrombosis in 4 (4%). Extrahepatic cause was counted in 57
      cases (53%) and was due to inflow of contrast material via nonmesenteric portal
      circulation through the gastric antrum, duodenum, and/or pancreas. CONCLUSION:
      Intrahepatic portal veins are frequently opacified during CTHA, and the causes
      were arterioportal shunts through hepatocellular carcinoma, postbiopsy shunt,
      portal vein thrombosis, and inflow of contrast material via the nonmesenteric
      portal circulation.

PMID- 11242217
TI  - CT features of primary colorectal signet-ring cell carcinoma.
AB  - PURPOSE: The purpose of this work was to evaluate the CT features of 15 patients
      with primary colorectal signet-ring cell carcinomas. METHOD: We retrospectively
      reviewed the CT scans of 15 patients (mean age 44 years) with pathologically
      proved colorectal signet-ring cell carcinoma. On CT, we evaluated the site and
      length of the tumor, bowel wall thickening patterns, perirectal or pericolic
      infiltration, the presence or absence of colonic obstruction, and metastasis to
      other organs. RESULTS: The tumors were located in the rectum in nine patients,
      the sigmoid colon in one, the hepatic flexure in one, the transverse colon in
      one, the ascending colon in two, and the cecum in one. The tumor length ranged
      from 4.0 to 10.0 cm (mean 6.1 cm) with mean thickness of 2.1 cm. CT showed
      concentric bowel wall thickening in all patients ("even" in 8 and "uneven" in 7),
      target appearance was noted in 4, perirectal or pericolic infiltrations were
      moderate to severe in 12, and colorectal obstruction was seen in 6. In the tumor
      spread patterns, lymphadenopathy was noted in 13, invasion to adjacent pelvic
      organs in 5, peritoneal carcinomatosis in 4, liver metastasis in 2, and
      periureteric metastasis in 1. CONCLUSION: Primary signet-ring cell colorectal
      carcinoma should be included for differential consideration when CT shows a long
      length of concentric bowel wall thickening and target sign, especially when such
      findings occur in the rectum and in young patients.

PMID- 11242218
TI  - Hepatic capsular retraction: unusual finding of cavernous hemangioma.
AB  - We report a case of hepatic giant hemangioma, which showed hepatic capsular
      retraction on CT and MRI. Pathologic examination revealed fibrosis combined with
      hemangioma, especially in a subcapsular location, which was responsible for the
      capsular retraction.

PMID- 11242219
TI  - Hepatic capsular retraction secondary to involuting cavernous hemangioma.

PMID- 11242220
TI  - Renal pseudotumors due to fat necrosis in acute pancreatitis.
AB  - Retroperitoneal fat necrosis is a well-known complication of acute pancreatitis.
      We describe an unusual case of fat necrosis presenting as multiple, bilateral
      renal pseudotumors in a patient with acute pancreatitis. The imaging findings on
      CT and MR are discussed.

PMID- 11242221
TI  - CT appearance of gastric involvement in multifocal idiopathic fibrosclerosis.
AB  - Multifocal idiopathic fibrosclerosis (also called multifocal fibrosclerosis) is
      an uncommon disease in which there is a systemic overgrowth of fibrous tissues,
      with a spectrum of aggressiveness ranging from benign retroperitoneal fibrosis to
      pachymeningitis. We describe the first case of gastric involvement of multifocal
      fibrosclerosis and its appearance on CT.

PMID- 11242222
TI  - High resolution MRI of the brainstem at 8 T.
AB  - A recently developed ultra high field MRI system operating at 8 T (UHFMRI) was
      applied for brainstem imaging. UHFMRI was performed in five healthy volunteers
      (three men, two women; age range 34--46 years). Sagittal and axial slices were
      obtained with the following settings: GE, TR 750--1,000 ms, TE 7-9 ms, FOV 20 cm,
      matrix 1,024 x 1,024 or 512 x 512 points, slice thickness 2 mm, resolution 195 or
      390 microm/pixel. The brainstem structures were assigned based on anatomy and
      course. Images with good signal strength and homogeneity were acquired from the
      midbrain and the pons. Main intraaxial structures could be directly visualized.
      The periaqueductal gray matter and nuclei had higher signal intensity than the
      predominantly white matter structures such as the
      corticobulbar/corticopontine/corticospinal tracts, the sensory lemnisci, and the
      medial longitudinal fasciculus. Structures with high iron content such as the
      substantia nigra and the red nucleus were seen as prominent signal
      hypointensities. Numerous vessels traversing the brainstem including small
      perforators were also distinguished. It is concluded that UHFMRI enables the
      acquisition of high quality images of the upper brainstem with details
      approaching that of histologic specimen.

PMID- 11242223
TI  - Diffusion-weighted MRI: detection of cerebral ischemia before and after carotid
      thromboendarterectomy.
AB  - PURPOSE: Conventional postoperative evaluation of patients following carotid
      thromboendarterectomy (TEA) consists of a clinical neurologic examination to
      assess neurologic deficits, color duplex ultrasound to document the surgically
      reestablished patency of the carotid artery, and CT for exclusion of
      postoperative ischemic infarctions. Recent studies prove that diffusion-weighted
      MRI is more sensitive in the detection of fresh insults than conventional MRI and
      CT. The objective of the study was to ascertain the incidence of clinically
      asymptomatic peri-and postoperative ischemic infarctions visualized at MRI.
      METHOD: We included 52 patients in the study. Fifty-one patients (31 men, 20
      women; average age 68 years) underwent cranial MR examination including a
      diffusion-weighted sequence at 24 h prior to carotid TEA and again 24 h following
      the procedure. One patient did not agree to participate. RESULTS: In 29 of 51
      patients (56%), neither the pre-nor the postoperative MR scans showed any
      diffusion abnormalities. In 16 patients (31%), however, preoperative MRI detected
      fresh ischemic insults. In nine patients (17.6%), the size of the insult resulted
      in surgery being postponed for 4 weeks. In six patients (11.8%), postoperative
      MRI returned findings of fresh disturbances of diffusion suggestive of ischemia
      that were not visualized on preoperative scans. Discrete neurologic deficits were
      observed in only two (3.9%) of these patients. Deficits were transient and
      disappeared within 72 h. CONCLUSION: Our findings underscore MRI's capacity for
      visualizing perioperative ischemic events. Moreover, MRI provides evidence of
      clinically asymptomatic embolisms that occur perioperatively.

PMID- 11242224
TI  - Evaluation of a FLAIR sequence designed to reduce CSF and blood flow artifacts by
      use of k-space reordered by inversion time at each slice position (KRISP) in high
      grade gliomas of the brain.
AB  - The objective of this study was to compare conventional and KRISP (k-space
      reordered by inversion time at each slice position) fluid-attenuated inversion
      recovery (FLAIR) sequences in high grade gliomas for artifact control,
      conspicuity of intracranial structures, and lesions as well as sensitivity to
      contrast enhancement. Artifacts were lower with the KRISP FLAIR sequence, and the
      conspicuity of all assessed structures and lesions was better. The degree of
      contrast enhancement was similar with T1-weighted and KRISP FLAIR sequences.

PMID- 11242225
TI  - Spinal epidural cavernous hemangioma: MR findings.
AB  - PURPOSE: Cavernous hemangiomas with a spinal epidural location are very uncommon
      vascular tumors in contrast to those in the vertebral body. The purpose of this
      study was to describe the radiologic findings, focusing on the MR studies, of
      spinal epidural cavernous hemangiomas. METHOD: Five pathologically proven cases
      of spinal epidural cavernous hemangioma were retrospectively reviewed. MR (n = 5)
      and CT (n = 1) were evaluated. RESULTS: The level was thoracic (n = 4) or
      lumbosacral (n = 1). The mass was located in the epidural space and showed
      paravertebral extension in all cases. It showed a lobulated contour in all cases
      and encircled the spinal cord partially with a larger posterior (n = 3) or
      anterior (n = 1) component in four cases. In all cases, the mass showed high
      signal intensity on T2-weighted images and homogeneous, strong enhancement.
      Adjacent bony erosion (n = 5) and intervertebral neural foraminal widening (n =
      4) were common. CONCLUSION: Spinal epidural cavernous hemangioma shows
      characteristic MR findings of a lobulated contoured epidural mass partially
      encircling the spinal cord with a larger posterior component in the spinal canal,
      high signal intensity on T2-weighted images, and homogeneous, strong enhancement.

PMID- 11242226
TI  - A comparative study between MR sialography and salivary gland scintigraphy in the
      diagnosis of Sjogren syndrome.
AB  - PURPOSE: The purpose of this work was to compare the diagnostic accuracy of MR
      sialography with that of salivary gland scintigraphy in Sjogren syndrome. METHOD:
      One hundred thirty patients clinically suspected of having Sjogren syndrome were
      examined by MR sialography and salivary gland scintigraphy. A labial gland biopsy
      was performed in all patients. Imaging findings of MR sialography and salivary
      gland scintigraphy were compared with the results of labial gland biopsy.
      RESULTS: From the results of labial gland biopsy, the diagnosis of Sjogren
      syndrome was established in 80 patients. Abnormally high T2 signal intensity
      areas on MR sialography and decreased uptake and delayed excretion of
      [(99m)Tc]pertechnetate on salivary gland scintigraphy were well seen in patients
      with Sjogren syndrome. For the diagnosis of Sjogren syndrome, salivary gland
      scintigraphy showed higher sensitivity than MR sialography. On the other hand, MR
      sialography showed higher specificity and positive predictive value (PPV) than
      salivary gland scintigraphy. Overall diagnostic accuracy was 83% for MR
      sialography and 72% for salivary gland scintigraphy. CONCLUSION: The high PPV of
      MR sialography suggests that MR sialography is the preferred imaging modality in
      patients suspected of having Sjogren syndrome.

PMID- 11242227
TI  - MRI of chronic recurrent parotitis in childhood.
AB  - PURPOSE: Chronic recurrent parotitis (CRP) is a rare inflammatory disease
      characterized by multiple episodes of unilateral or bilateral parotid
      inflammation over a period of years. The objective of this study was to evaluate
      the parotid glands using MRI during acute inflammation as well as during symptom
      free intervals. METHOD: Twelve children with a history of CRP were included. Four
      patients were examined during the acute phase and eight children during symptom
      free intervals. MR findings were correlated with the clinical status. RESULTS:
      Two different patterns were identified by MRI: acute inflammation versus chronic
      inflammation. Contrast enhancement of the parotid gland indicated acute
      inflammation. Cysts due to chronic inflammation were encountered in children who
      suffered multiple episodes of inflammation. CONCLUSION: Our findings suggest that
      CRP is characterized by recurrent, acute exacerbations of inflammation, resulting
      in a slowly progressive destruction of the parotid gland.

PMID- 11242228
TI  - Creutzfeldt-Jakob disease: serial changes on diffusion-weighted MRI.
AB  - We present serial changes on diffusion-weighted MRI (DWI) in a patient with
      Creutzfeldt-Jakob disease (CJD). DWI revealed serial changes of abnormal
      hyperintense lesions that had become more extensive and conspicuous with
      progression of neurologic findings, more sensitively than conventional MRI. In
      the late stage, disappearance of abnormal hyperintense lesions on DWI was
      observed. DWI proved to be particularly useful for monitoring the progression of
      CJD.

PMID- 11242229
TI  - Volumetric quantification of coronary artery calcifications using dual-slice
      spiral CT scanner: improved reproducibility of measurements with 180 degrees
      linear interpolation algorithm.
AB  - PURPOSE: The purpose of this work was to determine the reproducibility of
      coronary total calcium score (TCS) with dual-slice helical CT and compare three
      acquisition protocols. METHOD: Fifty patients (59 +/- 10 years old) underwent
      dual-slice helical CT (collimation = 2 x 2.5 mm) and coronary angiography. Two
      successive scans were performed, resulting in three sets of images: pitch = 1,
      360 degrees linear interpolation (LI) (A360); pitch = 1, 180 degrees LI (A180);
      and pitch = 1.5, 180 degrees LI (B180). TCS values, calculated using a volumetric
      method with a threshold of 90 HU, were compared, and the interscan variation was
      determined. Diagnostic performances were compared with receiver operating
      characteristic curves. RESULTS: Protocol A360 provided significantly lower TCS
      than protocols A180 and B180 (p < 0.0001). No statistical difference was seen
      between A180 and B180, which provided the lowest interscan variation (40 +/-
      58%). However, no significant clinical impact of the observed interscan
      variations was found. CONCLUSION: Reproducibility of TCS with dual-slice helical
      CT is improved by the 180 LI algorithm. However, dual-slice helical CT is not
      sufficiently reproducible to allow serial quantification of TCS over time.

PMID- 11242230
TI  - Accuracy of predicting and controlling time-dependent aortic enhancement from a
      test bolus injection.
AB  - PURPOSE: The purpose of this work was to determine the accuracy of predicting
      arterial enhancement from peripheral versus central venous test bolus injections
      at CT angiography (CTA). METHOD: In 40 patients with abdominal aortic aneurysms,
      aortoiliac enhancement profiles were predicted by mathematical deconvolution of
      the time-attenuation response to a 16 ml test bolus injection. Injection sites
      were either a cubital vein (n = 20) or a central venous injection site (n = 20).
      The accuracy of predicting enhancement was quantified as the "off-predicted
      deviation" (calculated as mean squared differences between observed minus
      predicted enhancement values) in all patients. RESULTS: Off-predicted deviation
      was significantly smaller in the central venous injection group (17 +/- 6 HU)
      than the peripheral injection group (33 +/- 18 HU) (p < 0.001). CONCLUSION:
      Arterial enhancement at CTA can be mathematically predicted and controlled more
      accurately if a central venous injection site is used. Automated saline flushing
      of the veins might improve the accuracy of the mathematical model for peripheral
      injections.

PMID- 11242231
TI  - Useful CT findings for predicting the progression of aortic intramural hematoma
      to overt aortic dissection.
AB  - PURPOSE: The purpose of this work was to assess useful CT findings for predicting
      the progression of aortic intramural hematoma to aortic dissection. METHOD: We
      analyzed the CT findings of 29 patients with aortic intramural hematoma with
      regard to the following: involved site, maximum thickness of hematoma, presence
      or absence of compression of true lumen, and pericardial and pleural effusion. CT
      findings were compared with those of the patients who progressed to aortic
      dissection (Group I) and those who did not (Group II). Each CT finding was
      evaluated with independent t test and Mann-Whitney U test (p < 0.05). RESULTS:
      Seven of 8 cases of Type A aortic intramural hematoma and 3 of 21 cases of Type B
      aortic intramural hematoma progressed to aortic dissection. The type of aortic
      intramural hematoma, maximum thickness of hematoma, compression of true lumen,
      and pericardial or pleural effusion were significantly different in Groups I and
      II. CONCLUSION: Type A aortic intramural hematoma, maximum thickness of hematoma,
      compression of true lumen, and pericardial or pleural effusion are the useful CT
      findings for predicting the progression of aortic intramural hematoma to aortic
      dissection.

PMID- 11242232
TI  - Accuracy of plastic replica of aortic aneurysm using 3D-CT data for transluminal
      stent-grafting: experimental and clinical evaluation.
AB  - PURPOSE: To plan stent-grafting for aortic aneurysms with complicated morphology,
      we prepared life-sized aortic replicas by laser stereolithography using helical
      3D--CT data. The accuracy of the replica was evaluated by measurement of vessel
      phantoms and clinical 3D--CT data. METHOD: An imaginary aortic wall was created
      from helical CT images of the aorta, and a hollow plastic replica was produced by
      laser stereolithography. The accuracy of the replica was evaluated in five
      abdominal aortic aneurysms by experimental phantom studies and measurements of
      the replicas. RESULTS: The mean difference in measurements between 3D--CT images
      and model vessels and between 3D--CT images and aortic replicas was 0.2 mm each.
      Therefore, the difference in measurements between real aortic aneurysms and the
      replicas was at most 0.4 mm. CONCLUSION: The accuracy of the replica is
      satisfactory, making it useful for preoperative evaluation and simulation for
      stent-grafting.

PMID- 11242234
TI  - Minute pulmonary meningothelial-like nodules: thin-section CT appearance.
AB  - Minute pulmonary meningothelial-like nodules are often incidentally discovered
      during pathologic evaluation of pulmonary parenchymal specimens. These lesions
      were once thought to represent pulmonary chemodectomas, but pathological studies
      have shown that they are not of neuroendocrine origin. Minute pulmonary
      meningothelial-like nodules are benign, perhaps reactive in nature, but are
      occasionally found in association with lung carcinoma. They may appear as
      randomly distributed well-defined micronodules on thin-section chest CT, and thus
      may simulate metastatic disease when associated with lung carcinoma.

PMID- 11242233
TI  - Crescent sign in invasive pulmonary aspergillosis: frequency and related CT and
      clinical factors.
AB  - PURPOSE: The aim of our study was to evaluate the frequency of the crescent sign
      on follow-up radiographs in patients with invasive pulmonary aspergillosis,
      correlated with initial CT and clinical findings. METHOD: Retrospective analysis
      of serial chest radiographs was performed to see the frequency of the crescent
      sign in 21 consecutive patients with pathologically proved invasive pulmonary
      aspergillosis. The appearance of the crescent sign was correlated with the
      pattern of parenchymal lesions on initial CT scans, the presence and duration of
      neutropenia, and underlying diseases. RESULTS: The crescent sign was seen in 10
      of 21 patients (48%) on follow-up radiographic examinations. It was seen in
      patients with initially large [consolidation or mass; 9/11 (82%) patients] rather
      than small [nodule(s); 1/10 (10%) patients] parenchymal lesions (p = 0.002) on
      CT. The sign appeared in 7 of 17 (41%) patients with neutropenia 1-10 days after
      recovery from neutropenia. It appeared in three of four patients (75%) without
      neutropenia 4--8 days after treatment with amphotericin B. The appearance was not
      related to the duration (32 days in patients with crescent sign and 17 days
      without sign) of the neutropenic period (p > 0.05). The sign was seen in 8 of 15
      (53%) patients with acute myelogenous leukemia and 2 of 6 (33%) patients with
      other diseases (p > 0.05). CONCLUSION: The crescent sign appears in about half of
      patients with invasive pulmonary aspergillosis with recovery from neutropenia,
      especially when the initial lesion is a consolidation or mass on CT scans.

PMID- 11242235
TI  - Localization of pulmonary nodules using suture-ligated microcoils.
AB  - Percutaneous localization of pulmonary nodules in five patients was performed
      utilizing suture-ligated embolization microcoils and CT guidance. Each
      localization was performed prior to video-assisted thoracoscopic wedge resection
      of the targeted nodules. Each suture-ligated microcoil was placed within 1.0 cm
      of the targeted pulmonary nodule. The attached suture served as a guide to direct
      accurate resection of the nodules. This technique is easily performed and
      provides a reliable alternative to nodule localization prior to thoracoscopic
      resection.

PMID- 11242236
TI  - Malignant hemangiopericytoma of the breast.
AB  - A55-year-old woman presented with 1-year history of mass in the right breast.
      Incisional biopsy showed the tumor to be malignant hemangiopericytoma from its
      histology. The tumor showed low--intermediate density and peripheral contrast
      enhancement on CT, and inhomogeneous mixed-signal intensity both on T1W and T2W
      images, and peripheral enhancement with Gd-DTPA on MRI with no invasion of the
      duct.

PMID- 11242237
TI  - Sectional neuroanatomy of the upper limb III: forearm and hand.
AB  - This paper is the last of three articles that describe the functional anatomy of
      the upper limb. It extends the series by presenting the axial anatomy of the
      forearm and hand. In addition, it provides a table that defines the patterns of
      muscle denervation specific to six representative sites. This set of articles is
      clinically useful because it can be used to rapidly identify and describe the
      innervation of the muscles and skin of the upper limb.

PMID- 11242238
TI  - Olecranon fractures in 26 children with mean follow-up of 59 months.
AB  - The authors report clinical and radiologic results of a series of 26 children who
      sustained an olecranon fracture, reviewed with a mean follow-up of 59 months.
      Mean age at time of trauma was 9 years. Direct trauma was the most common
      mechanism, and a radial head fracture was associated in one third of the cases.
      The fracture type usually consisted of a single fracture line, with a
      displacement >2 mm in one third of the cases. Treatment was usually conservative
      for nondisplaced or minimally displaced fractures, whereas open reduction with
      tension-wire pinning was proposed for displaced fractures. Clinical results were
      good, but radiologic results were less satisfying because of residual
      displacement on postoperative reviews. There was no functional impairment at
      final follow-up. Three patients from the surgically treated group with associated
      radial head fractures demonstrated a growth disturbance, possibly related to an
      ischemic cause.

PMID- 11242239
TI  - Role of computed tomography in the classification and management of pediatric
      pelvic fractures.
AB  - In adults, pelvic computed tomography (CT) scanning plays an important role in
      the treatment of pelvic fractures; however, the role of CT scanning in the
      management of pediatric pelvic fractures is unclear. The purpose of this study
      was to investigate the efficacy of CT scanning in the management of pelvic
      fractures in children. One hundred three consecutive patients were identified.
      All patients underwent anteroposterior plain radiographic evaluation; CT scans
      were performed in 62. Three orthopaedic surgeons independently reviewed the plain
      radiographs and determined fracture classification and management. Subsequently,
      each observer was shown corresponding CT scans and again determined
      classification and management. Interobserver agreement was calculated using Kappa
      statistics. After the addition of CT scans, the mean changes in classification
      were nine (15%) and in management two (3%). Plain radiographs alone reliably
      predicted the need and type of operative intervention. Kappa statistics
      demonstrated "excellent" agreement for classification and management without and
      with CT scans. We reliably determined fracture classification and management
      based on plain radiographs alone.

PMID- 11242240
TI  - Toddler's fracture: presumptive diagnosis and treatment.
AB  - The diagnosis of a toddler's fracture is frequently difficult at the initial
      evaluation because of negative radiographs. We propose the presumptive diagnosis
      of toddler's fracture, despite negative radiographs, when the history and
      physical examination are consistent with the diagnosis. This retrospective study
      was designed to evaluate how frequently the diagnosis is correct and to determine
      if there were any differentiating characteristics with respect to history, gait,
      or physical examination. Thirty-nine children were presumptively diagnosed with
      toddler's fracture. A total of 16 (41%) toddler's fractures was confirmed on
      follow-up radiographs. Comparing the children who demonstrated a toddler's
      fracture with those who did not, no particular characteristic was found that
      could predict the outcome. To avoid delay in the treatment of toddler's fracture,
      we recommend a long-leg cast on those children with a history of an acute injury,
      inability to walk or limp, no constitutional signs, and negative radiographs.

PMID- 11242241
TI  - Open reduction and internal fixation for supracondylar humerus fractures in
      children.
AB  - Eight hundred sixty-two supracondylar humerus fractures were treated between
      January 1984 and July 1997. Sixty-five (8%) patients were managed with open
      reduction and internal fixation with pins. The remaining 797 patients (92%) were
      managed with either casting, closed reduction with or without percutaneous
      pinning, or traction. Of the 65 patients managed with open reduction, 46 (71%) of
      these fractures were irreducible, 16 (24%) had associated vascular compromise,
      eight (12%) were open, and one was associated with a postreduction nerve palsy
      and nonanatomic reduction. According to the criteria of Flynn et al. 18 (55%)
      elbows were rated excellent, eight (24%) were rated good, three (9%) were rated
      fair, and four (12%) were rated poor after an average of 5.8 months postinjury.
      This study indicates that highly satisfactory results can be obtained in severely
      displaced fractures managed with open reduction in these situations.

PMID- 11242242
TI  - Radiologic evaluation of juvenile tillaux fractures of the distal tibia.
AB  - This study evaluated the accuracy of plain radiographs and computerized
      tomography (CT) in assessing juvenile Tillaux fractures of the distal tibia. A
      simulated Tillaux fracture was made in four cadaver specimens and displaced 0, 1,
      2, 3, and 5 mm. Plain radiographs and CT were performed on each specimen at each
      amount of displacement, and the results were compared with the actual amount of
      displacement present. Plain radiographs and CT were accurate within 1 mm in
      depicting the actual fracture displacement about 50% of the time. CT was more
      sensitive than plain radiographs in detecting fractures with >2 mm of
      displacement. Fracture displacement of >2 mm is generally considered an
      indication for fracture reduction. Because of its sensitivity in detecting
      fractures displaced >2 mm, CT is the preferred imaging modality in the assessment
      of juvenile Tillaux fractures.

PMID- 11242243
TI  - School sports accidents: analysis of causes, modes, and frequencies.
AB  - About 5% of all school children are seriously injured during physical education
      every year. Because of its influence on children's attitude toward sports and the
      economic aspects, an evaluation of causes and medical consequences is necessary.
      In this study, 213 school sports accidents were investigated. Besides diagnosis,
      the localization of injuries, as well as the duration of the sick leave were
      documented. Average age of injured students was 13 years. Most of the injured
      students blamed themselves for the accident. The most common injuries were
      sprains, contusions, and fractures. Main reasons for the accidents were faults in
      basic motion training. Playing soccer and basketball were the most frequent
      reasons for injuries. The upper extremity was more frequently involved than the
      lower extremity. Sports physicians and teachers should work out a program
      outlining the individual needs and capabilities of the injured students to
      reintegrate them into physical education.

PMID- 11242244
TI  - Steindler flexorplasty of the elbow in obstetric brachial plexus injuries.
AB  - A Steindler flexorplasty at the elbow was performed in 26 patients with an
      obstetric brachial plexus lesion because of deficient elbow flexion. Follow-up
      after a mean of 2.9 years (range, 1-7 years) showed a good functional result in
      23 cases, whereas 3 primary failures were noted. In one case, a recurrent
      dislocation of the elbow was seen 3 years after the initial flexorplasty.
      Steindler flexorplasty is a comparatively simple operation and gives very
      reliable results. It should be preferred above other, more elaborate muscle
      transfers for loss of elbow flexion.

PMID- 11242245
TI  - Development of the acetabulum in patients with slipped capital femoral epiphysis:
      a three-dimensional analysis based on computed tomography.
AB  - Orientation and shape of the acetabulum were determined by the use of three
      dimensional reconstruction of computed tomography (CT) data sets in 22 patients
      with a total of 30 slipped capital femoral epiphyses. We developed an interactive
      three-dimensional software program to measure the anteversion and inclination of
      the acetabulum without projectional and pelvis-tilting errors. Furthermore, we
      determined the height, width, depth, volume, and surface of the acetabulum as
      parameters describing the acetabular shape. Comparison of the affected side with
      the contralateral unaffected hip showed no significant differences for acetabular
      orientation and shape. The relationship between the degree of the slip and the
      acetabular orientation was calculated. No correlation was found. Based on the
      results of this study, we conclude that the slipping of the capital femoral
      epiphysis has no influence on acetabular development.

PMID- 11242246
TI  - Three-dimensional analysis of the proximal femur in patients with slipped capital
      femoral epiphysis based on computed tomography.
AB  - A three-dimensional (3D) analysis based on computed tomography was performed to
      study the 3D geometry of the proximal femur in cases of slipped capital femoral
      epiphysis (SCFE). For this purpose, new interactive software was developed to
      analyze hip joint geometry using 3D models without pelvis tilting and projected
      errors. Twenty-two patients, 8 girls and 14 boys, with a total of 30 slipped
      capital femoral epiphyses, were reviewed. In the affected hips, we observed a
      reduced femoral anteversion of 7.0 degrees (vs. 12.7 degrees) and a reduced
      femoral shaft neck angle of 134.2 degrees (vs. 141.0 degrees). In response to
      these results, we suggest that an SCFE is associated with reduced femoral
      anteversion and a reduced femoral shaft neck angle.

PMID- 11242247
TI  - Biomechanical analysis of compression screw fixation versus standard in situ
      pinning in slipped capital femoral epiphysis.
AB  - A slipped capital femoral epiphysis was created in 12 matched pairs of immature
      bovine femora using an anterior-to-posterior-directed shear force. All soft
      tissues, with the exception of the perichondrial ring, were removed before
      testing. One specimen from each pair was fixed with a single cannulated screw in
      standard fashion, whereas the contralateral specimen was fixed with a single
      screw that compressed the physis. The amount of compression achieved was
      quantified using Fuji film. Standard fixation yielded 1.4 MPa of pressure across
      the physis; compression fixation yielded 3.2 MPa, a 2.3-fold difference (p =
      0.0001). The compression fixation was 47% more stiff than standard technique (p =
      0.030), yet the differences in ultimate strength (p = 0.180) and energy absorbed
      at failure (p = 0.910) were not statistically significant. The stiffness of the
      compressed specimens remained less than that of the intact femora. Single-screw
      compression fixation of in vitro bovine femora was significantly more stiff than
      the current, widely used noncompression fixation technique, yet does not
      compromise the ultimate strength, energy absorbed, or the technical ease of
      single-implant fixation.

PMID- 11242248
TI  - Osteonecrosis of the femoral head associated with slipped capital femoral
      epiphysis.
AB  - We performed a retrospective analysis of 212 patients (299 hips) with slipped
      capital femoral epiphysis (SCFE) over a 9-year period to assess the incidence of
      osteonecrosis of the femoral head. Risk factors for the occurrence of
      osteonecrosis and the influence of treatment on the development of osteonecrosis
      were determined. Osteonecrosis occurred in 4 hips with unstable SCFE (4/27) and
      did not occur in hips with stable SCFE (0/272). The proportion of hips in which
      osteonecrosis developed was significantly higher among the unstable hips (4/27
      vs. 0/272, p < 0.0001). Among those with an unstable hip, younger age at
      presentation was a predictor of a poorer outcome. Magnitude of the slip,
      magnitude of reduction, and chronicity of the slip were not predictive of a
      poorer outcome in the unstable group. In situ fixation of the minimally or
      moderately displaced "unstable" SCFE demonstrated a favorable outcome. We have
      identified the hip at risk as an unstable SCFE. The classification of hips as
      unstable if the epiphysis is displaced from the metaphysis or if the patient is
      unable to walk is most useful in predicting a hip at risk for osteonecrosis.

PMID- 11242249
TI  - Hip arthrodesis in adolescents using external fixation.
AB  - Between 1994 and 1998, seven adolescents underwent hip arthrodesis with the use
      of an external fixator. Mean time of follow-up was 24.0 months after surgery. The
      duration of fixation and time to fusion were 6.6 months (range, 5-9.5 months) and
      8.0 months (range, 5.2-15 months), respectively. At most recent follow-up, there
      was a significant improvement in the mean modified Harris hip score, in which the
      maximum score is 91 points after omitting 9 points for hip range of motion and
      deformity, from 25.7 before surgery to 66.7 after surgery (p < 0.01). The
      advantages of this procedure include (i) the ease and accuracy of obtaining the
      proper position for fusion, (ii) the ability to lengthen the affected leg at the
      same time, (iii) the diminished likelihood of compromising future hip operations,
      and (iv) the ability to ambulate and bear weight throughout the treatment course.
      We recommend this method of hip arthrodesis with external fixation for patients
      with intractable hip pain necessitating this procedure.

PMID- 11242251
TI  - Development of hip dysplasia in hereditary multiple exostosis.
AB  - In approximately 25% of patients with hereditary multiple exostosis, there is an
      abnormal osteochondral formation localized in the femoral proximal metaphysis.
      This formation often causes a mechanically progressive insufficiency of the
      acetabular cavity, a true developmental hip dysplasia, that together with a coxa
      valga deformity, which is also present, causes a gradual deterioration in the
      relations of this joint. This malformation has a poor prognosis and is difficult
      to manage. Although this entity is rather frequent and quite severe, it is rarely
      found in the medical literature. The author describes six private cases, taken
      from a total of 24,000 patients (0.25/1000) as examples of this entity, and
      provides a review of the literature.

PMID- 11242250
TI  - Results of femoral varus osteotomy in children older than 9 years of age with
      Perthes disease.
AB  - We review the results of varus osteotomy in 17 patients older than 9 years of age
      with 18 hips affected by Perthes disease. Seventeen hips were judged as Catterall
      3 or 4, and 14 hips had partial or complete loss of the lateral pillar. At an
      average follow-up of 10 years (4.2-17.8 years), 3 hips were rated Stulberg 1, 3
      were Stulberg 2, 4 were Stulberg 3, and 8 were Stulberg 4 or 5. At follow-up, 7
      hips were considered good or fair based on the use of Mose circles. Statistical
      analysis indicated better results in patients younger than 10 years of age
      compared with those older than 10 years of age. Varus osteotomy as a method of
      containment for Perthes disease provides improved results in children older than
      9 years compared with natural history studies or studies of noncontainment
      methods. However, it seems likely that there is an upper age limit for
      effectiveness of containment treatment.

PMID- 11242252
TI  - Comparison of the posterior approach versus the dorsal approach in the treatment
      of congenital vertical talus.
AB  - The purpose of this study was to compare retrospectively the results of a single
      stage dorsal approach versus the posterior approach for the surgical treatment of
      congenital vertical talus (CVT) at a single institution. Twenty-four patients (33
      feet) with CVT were treated surgically between 1960 and 1998. Eighteen patients
      (25 feet) underwent a posterior release (group 1), and six patients (eight feet)
      underwent surgery via the dorsal approach (group 2). All patients were evaluated
      at a minimal follow-up of 3 years. Preoperative and follow-up radiographs were
      evaluated, and a modified version of the clinical score by Adalaar was used.
      Group 1 had 45 procedures on 25 feet, whereas group 2 had no repeated or revision
      operations. The clinical score was 6.75 for group 1 and 8.0 for group 2.
      Tourniquet time was 123 minutes and 87 minutes for groups 1 and 2, respectively.
      Twelve group 1 patients (48%) had avascular necrosis (AVN) versus none of the
      group 2 patients. Both groups had similar preoperative and postoperative
      radiographic measurements. Both approaches were able to reduce successfully the
      talonavicular joint; however, the single-stage dorsal incision group required
      significantly less operative time, had better clinical scores, and had fewer
      complications 3 years after surgery.

PMID- 11242253
TI  - Residual bone cysts after Ilizarov treatment of relapsed clubfeet.
AB  - The Ilizarov technique is well established as an effective method of treating
      clubfoot deformities. A complication of this method is the development of cysts
      in the bones of the foot. The purpose of this study was to clarify the incidence,
      presentation, and etiology of these cysts. The radiographs of 17 feet that had
      undergone Ilizarov treatment for a clubfoot deformity were reviewed. In nine of
      the feet, discrete, well demarcated lucencies of bone were detected. They
      occurred in both tarsal and metatarsal bones, but most commonly in the base of
      the fifth metatarsal. Magnetic resonance imaging examination of two feet
      demonstrated a normal marrow signal. suggesting that the cysts are due to
      localized trabecular resorption with the space being filled with marrow fat.

PMID- 11242254
TI  - Avascular necrosis of the talus after McKay clubfoot release for idiopathic
      congenital clubfoot.
AB  - Avascular necrosis of the talus is a serious potential complication of clubfoot
      surgery. In the few cases described in the literature, the necrosis has involved
      the entire talus and resulted in progressive fragmentation and collapse. Serial
      postoperative radiographs of 96 idiopathic clubfeet in 70 patients are reviewed
      here to determine the incidence of avascular necrosis after McKay soft tissue
      release. Based on criteria in the literature for making the diagnosis, no cases
      of avascular necrosis were seen. Growth lines were observed in the cuboids and
      calcanei of all the feet during the follow-up period. Eight feet failed to
      develop growth lines in the talus during follow-up. Five of these feet showed
      flattening of the dome of the talus and three hypoplasia of the talar head and
      neck at the most recent follow-up. Absence of normal growth lines in the talus
      after operation seems to predict talar abnormalities.

PMID- 11242255
TI  - Footprint and radiographic analysis of the feet.
AB  - There is controversy concerning the definition and measurement of the medial
      longitudinal arch of the foot. Various techniques are reported to assess the
      medial arch height, including radiographic measurements and footprint analysis,
      which are the most commonly used methods. Some authors define footprint analysis
      as unreliable for measuring the arch height. The purpose of this study was to
      investigate the relationship between radiologically measured angles and the arch
      index obtained from footprint analyses in 38 children with flexible pes planus. A
      positive correlation of arch index was found between lateral talo-horizontal and
      lateral talo-first metatarsal angles (p < 0.05). These angles have been used by
      some authors to describe the height of the medial longitudinal arch of the foot.
      This study demonstrated that footprint analysis could be used effectively for
      screening studies and at individual office examinations.

PMID- 11242256
TI  - Nonspinal orthopaedic problems in familial dysautonomia (Riley-Day syndrome).
AB  - Familial dysautonomia (FD) is a rare autosomal recessive disease occurring in
      Ashkenazi Jews. It affects the autonomic, central, and peripheral nervous
      systems. The purpose of this study was to assess the prevalence and
      characteristics of orthopedic deformities, other than spinal deformities, in this
      population. A retrospective review of the medical records and radiographs of 182
      patients was made. Three main groups of orthopaedic conditions were evaluated:
      (a) Fractures: 60% of the patients had one or more fractures; the average
      fracture rate was 1.4/patient. (b) Neuropathic joints: 11% of the cases had one
      or more neuropathic joints, the knee being the most common. (c) Other
      musculoskeletal deformities: 26% of the patients had one or more deformities.
      Lower extremity rotational problems and foot anomalies accounted for most of
      these deformities. Patients with FD have a higher prevalence of fractures and
      neuropathic joints than do their peers. The fracture pattern also is different,
      with a higher incidence of proximal femoral fractures.

PMID- 11242257
TI  - Effect of lower limb Sofield procedure on ambulation in osteogenesis imperfecta.
AB  - Ambulation status was evaluated in 34 patients pre- and post-Sofield procedure in
      patients with osteogenesis imperfecta. Three percent had improved ambulation,
      42.4% remained the same and 54.6% were worse. Only 41.2% were ambulating
      postoperatively compared to 73.5% preoperatively. The Sofield procedure did not
      improve ambulation status.

PMID- 11242258
TI  - Functional outcome of Sofield procedure in the upper limb in osteogenesis
      imperfecta.
AB  - The functional outcome of Sofield procedures done in the upper limb of five
      patients with severe osteogenesis imperfecta was studied. Fourteen procedures
      were done. Mean follow-up was more than 10 years. Function of the upper limb
      improved in all patients. No patient lost function.

PMID- 11242259
TI  - Hemichondrodiastasis for the treatment of genu varum deformity associated with
      bone dysplasias.
AB  - Hemichondrodiastasis has been reported for treatment of angular deformities in
      children close to skeletal maturity. The use of distraction through the physis in
      younger children was not recommended. The authors report three children 3 to 7
      years of age who underwent bilateral proximal tibial hemichondrodiastasis for
      correction of genu varum due to bone dysplasia. Ilizarov external fixators were
      applied in all cases. The patients underwent gradual angular correction at a rate
      of 0.5 mm/d. Distraction was continued until a normal mechanical axis was
      achieved. Normal alignment was achieved in two patients and slight overcorrection
      in the third. The patients were followed for 3 to 11 years, and no adverse
      affects on the physis were identified. This is the first report of physeal
      distraction in patients this young. Our results are good, and we believe that
      hemichondrodiastasis can be safely used for correction of angular deformities in
      young children.

PMID- 11242260
TI  - Partial resection of the scapula and a release of the long head of triceps for
      the management of Sprengel's deformity.
AB  - Previous surgical methods to address Sprengel's deformity by an attempted
      relocation of the scapula have achieved a limited functional improvement. A novel
      method was devised that includes a partial scapular resection, a removal of any
      omovertebral communication, and a release of the long head of triceps from the
      scapula. The results of eight cases are presented in which this method was used
      on 5 males and 3 females patients (age range, 19 months to 9 years). Early
      postoperative, active-assisted motion exercises for the patients were encouraged.
      On average, flexion improved from 100 degrees to 175 degrees and abduction
      improved from 90 degrees to 150 degrees. In one patient, a second operation was
      performed to remove an exostosis that followed the primary procedure. Initially,
      two keloid scars followed the use of a curvilinear incision. However,
      subsequently, this problem was eliminated by the use of a transverse incision.
      The new method seems to provide highly favorable functional and cosmetic results
      with a low morbidity.

PMID- 11242261
TI  - Time course of osteocalcin, bone-specific alkaline phosphatase, and C-terminal
      procollagen peptide during callus distraction.
AB  - This study involved 15 patients who were undergoing extremity lengthening by
      callus distraction. Blood samples and radiographs of the callus distraction
      segment were obtained before surgery, every 2 weeks during the distraction phase,
      and every 4 weeks between the end of distraction and removal of the fixator. A
      digital radiograph analysis system was used to determine the radiographic density
      of the callus distraction segments. In addition, the serum parameters
      osteocalcin, bone-specific alkaline phosphatase, and C-terminal procollagen
      peptide (PICP) were evaluated. The radiographic density was constant during the
      distraction phase, but increased logarithmically during the consolidation period.
      Similar kinetics were observed for osteocalcin, with an average coefficient of
      correlation between these two parameters of 0.66+/-0.15. PICP levels rose rapidly
      after surgery and increased further during the consolidation period. Serum levels
      of bone-specific alkaline phosphatase were not uniform between patients, and
      there was no correlation to the kinetics of radiographic density or the other
      serum parameters. The similarity between radiographic density and osteocalcin
      kinetics, as well as the rapid postoperative increase in PICP, imply that further
      information may be obtained about osteoneogenesis from the study of these two
      serum parameters.

PMID- 11242262
TI  - Measurement of vertebral rotation in standing versus supine position in
      adolescent idiopathic scoliosis.
AB  - Thirty-three structural curves of 25 patients with adolescent idiopathic
      scoliosis were evaluated using computed tomography (CT) scans and plain
      radiography. The average Cobb angle on standing radiographs was 55.72 degrees and
      was observed to be corrected spontaneously to 39.42 degrees while the patients
      were in supine position (29.78% correction). Average apical rotation according to
      Perdriolle was 22.75 degrees on standing radiographs and 16.78 degrees on supine
      scanograms. The average rotation according to Aaro and Dahlborn on CT scans was
      16.48 degrees. Radiographic measurements were significantly different from axial
      CT slice or scanogram measurements (p = 0.000), but the two latter measurements,
      both obtained in the supine position, did not appear to be different (p = 0.495).
      Deformities on the transverse plane as well as on the coronal plane are
      influenced by patient positioning. If the patient lies supine, the scoliosis
      curve corrects spontaneously to some degree on both planes. Measurements obtained
      from the scanograms by the Perdriolle method in the supine position are very
      similar to those obtained by CT. Perdriolle's is a simple, convenient, and
      reliable method to measure rotation on standing radiograms.

PMID- 11242263
TI  - Radiographic evaluation of bowed legs in children.
AB  - Radiographic screening is widely used to distinguish between Blount disease
      (infantile tibia vara) and physiologic bowing. Thirteen children with Blount
      disease, evaluated before 3 years of age, with initial radiographs showing no
      sign of Langenskiold changes, were compared with 50 children with physiologic
      bowing, also evaluated before 3 years of age with similar radiographic studies.
      Screening test accuracy was determined retrospectively for measurement of the
      mechanical axis, the tibial metaphyseal-diaphyseal angle (TDMA), and the
      epiphyseal-metaphyseal angle (EMA). A radiographic screening method combining the
      TMDA and the EMA, using cutoff values of 10 degrees and 20 degrees respectively,
      exhibited the best combination of sensitivity, specificity, and positive
      predictive value, correctly identifying all cases of Blount disease and 40 of 50
      cases of physiologic bowing. Our data suggest that children between 1 and 3 years
      of age with TMDA <10 degrees, or TMDA > or =10 degrees and EMA < or =20 degrees,
      are at less risk for development of Blount disease. Children with TMDA > or =10
      degrees and EMA >20 degrees are at greater risk for development of Blount disease
      and should be followed closely.

PMID- 11242264
TI  - Normal development of the tibiofemoral angle in children: a clinical study of 590
      normal subjects from 3 to 17 years of age.
AB  - In evaluation of genu varum-genu valgum, tibiofemoral (TF) angle and
      intercondylar (IC) or intermalleolar (IM) distance are commonly measured. In this
      study, we determined mean values and normal limits for TF angle and IC/IM
      distance in 590 normal Turkish children (287 girls and 303 boys) aged from 3 to
      17 years using clinical methods. We noted a significantly higher degree of valgus
      angle than that in previous reports. The maximal mean valgus angle was 9.6
      degrees at 7 years for boys and 9.8 degrees at 6 years for girls. These
      differences were considered racial differences between Turkish children and those
      of other races. Turkish children, aged between 3 and 17 years, exhibited < or =11
      degrees physiologic valgus. A measurable varus angle or a valgus higher than 11
      degrees during this period should be considered abnormal.

PMID- 11242265
TI  - Thoughts on patient safety: how hospitals can become safe houses.

PMID- 11242266
TI  - Which implant for proximal femoral osteotomy in children?

PMID- 11242267
TI  - Assessment of clinical articles.

PMID- 11242268
TI  - Anterior cervical instrumentation enhances fusion rates in multilevel
      reconstruction in smokers.
AB  - This retrospective consecutive case study evaluated the effect of anterior
      plating on multilevel anterior cervical decompressions and fusions in smokers and
      non-smokers. Multilevel anterior cervical decompression and fusion surgery in
      smokers provides an important challenge. Higher nonfusion rates in smokers have
      been reported. Cigarette smoking has been shown to interfere with bone metabolism
      and revascularization and to suppress bone formation. One hundred six patients
      underwent anterior cervical decompression and fusion using autografts or
      allografts and anterior plating. The minimum follow-up was 12 months. The mean
      age was 50.12 years (+/- 11.72; range, 27 to 80 years). Autografts were used in
      90 patients and allograft in 16. The mean level fused was 2.74 (+/- 0.61). Forty
      six (45.5%) patients were smokers. Successful fusion was achieved in all but
      three patients (97.17%). C5 root weakness was seen in four patients (3.8%); two
      patients experienced acute airway obstruction, of which one required tracheotomy.
      Temporary recurrent laryngeal nerve palsy developed in three (2.8%) patients. A
      fusion rate of 97% was achieved in multilevel anterior cervical decompression and
      fusions using anterior plating. No difference in fusion rates between smokers and
      nonsmokers was seen. Anterior cervical plating markedly improved the fusion rate
      in smokers.

PMID- 11242269
TI  - Cervical spondylosis: the role of anterior instrumentation after decompression
      and fusion.
AB  - The role of plate stabilization after anterior decompression and fusion of the
      cervical spine for cervical spondylosis remains controversial. This study aimed
      to justify the use of instrumentation to stabilize anterior cervical fusion for
      cervical spondylosis through a risk-benefit analysis and comparison of the
      results with those reported in the literature on the outcome of fusion without
      instrumentation. The authors retrospectively reviewed the charts and radiographs
      of 47 patients with symptoms secondary to cervical spondylosis who underwent
      anterior cervical decompression and instrumented fusion. After operation,
      patients were mobilized early, and neither neurologic injury nor infection
      developed in any patient. At an average 3.4 years after surgery, the rate of
      graft complications, including nonunion (4.26%), was low, whereas the rate of
      hardware-related morbidity was minimal (6%). An average 0.4 degrees loss of the
      intraoperative correction of cervical lordosis was observed at the last follow-up
      examination. Accelerated degenerative changes at levels adjacent to the fusion
      were seen in 17% of patients, but only two patients required repeat operation for
      persistent symptoms. The use of instrumentation to stabilize the cervical spine
      in patients with cervical spondylosis after anterior decompression and fusion is
      relatively safe. It permits early pain-free mobilization, successfully maintains
      sagittal cervical spine alignment, and promotes consistent and reliable spinal
      fusion.

PMID- 11242270
TI  - Comparison of biomechanical response to surgical procedures used for cervical
      radiculopathy: posterior keyhole foraminotomy versus anterior foraminotomy and
      discectomy versus anterior discectomy with fusion.
AB  - The objective of this study was to compare the change in flexibility of C5-C6
      caused by three procedures using a three-dimensional nonlinear finite element
      model: posterior foraminotomy (keyhole procedure), anterior foraminotomy with
      discectomy, and anterior discectomy with fusion. The keyhole procedure produced a
      minor increase in motion. The anterior foraminotomy and discectomy produced one
      to two times greater motion. Anterior discectomy with fusion produced 50% to 100%
      reduction in motion. The posterior keyhole foraminotomy has a much lesser effect
      on the stability of the cervical spine segment than does an anterior procedure,
      and fusion is a requisite part of the anterior decompression procedure.

PMID- 11242271
TI  - Kinematic evaluation of atlantoaxial joint instability: an in vivo
      cineradiographic investigation.
AB  - Although range of motion has been considered the best parameter to quantify
      atlantoaxial instability, no other kinematic parameters have been determined for
      dynamic quantification. The objectives of this study were to investigate the
      kinematics of the normal and pathologic atlantoaxial joints by cineradiography
      and to determine the in-vivo kinematic parameters, if any, for the quantification
      of atlantoaxial instability. Sagittal plane motion of the atlantoaxial joints was
      analyzed by cineradiography in 12 healthy volunteers and 15 patients with
      atlantoaxial subluxation. In both flexion and extension, C1-C2 sagittal rotation
      and C1 translation in the sagittal plane were measured continuously to determine
      the time-displacement curves for both parameters. All patients with atlantoaxial
      subluxation and seven of the volunteers had the sigmoid pattern in their time
      displacement curves in sagittal rotation. In these cases, atlantoaxial motion
      showed different points of the onset of rapid increase in motion in their sigmoid
      curves between flexion and extension. The discrepancy between these points was
      more significant in the patients than in the volunteers. In most of the patients
      who had atlantoaxial instability, subluxation occurred when the atlantoaxial
      joints were still in a more extended position and they were reduced when they
      were still in more flexed position. The discrepancy showed characteristics
      similar to those of the neutral zone observed during in vitro investigations,
      suggesting that it becomes a good indicator of in vivo atlantoaxial instability.

PMID- 11242272
TI  - Change of muscle motor-evoked potentials after motor cortex stimulation caused by
      acute spinal cord injury in cats.
AB  - The validity of the evoked compound muscle action potential (ECMAP) as an index
      of spinal cord injury has not been established in neurophysiologic monitoring of
      motor function, although evoked spinal cord potential (ESCP) has been. In the
      current study, nine cats were used. After craniotomy, electric stimuli were
      applied to the motor area. Four cats were given stimulation of various numbers
      and frequencies, and the other five cats underwent graded compression of the
      spinal cord, and then ECMAPs and ESCPs were recorded. Three cats were awakened
      and their motor functions were assessed 3 weeks later. The amplitude of the ESCP
      never decreased to 60% or less of the control value, even when ECMAPs
      disappeared. No motor dysfunction was present 3 weeks after the experiment. ECMAP
      is clinically useful, providing information on impairments of the spinal cord
      that otherwise would remain undetected.

PMID- 11242273
TI  - Thoracic pedicle: surgical anatomic evaluation and relations.
AB  - This anatomic study investigated the thoracic pedicle and its relations. The
      objective was to emphasize the importance of the thoracic pedicle for
      transpedicular screw fixation to avoid complications during surgery. Twenty
      cadavers were used to observe the cervical pedicle and its relations. The isthmus
      of the pedicle was exposed after removal of whole-posterior bony elements,
      including spinous processes, laminas, lateral masses, and the inferior and
      superior facets. The pedicle width and height, interpedicular distance, pedicle
      inferior nerve root distance, pedicle-superior nerve root distance, pedicle-dural
      sac distance, root exit angle, and nerve root diameter were measured. There was
      no distance between the pedicle and dural sac in eight specimens. There was,
      however, a short distance in 12 remaining specimens in the upper and lower
      thoracic regions. The distances between the thoracic pedicle and the adjacent
      nerve roots ranged from 1.5 to 6.7 mm and 0.8 to 6.0 mm superiorly and inferiorly
      at all levels. The mean pedicle height and width at T1-T12 ranged from 2.9 to
      11.4 mm and 6.2 to 21.3 mm, respectively. The interpedicular distance decreased
      gradually from T1 to T5 and then increased gradually to T12. The mean root exit
      angle decreased consistently from 104 degrees to 60 degrees. The nerve root
      diameter was between 2.3 and 2.5 mm at the T1-T5 level and then increased
      consistently from 2.5 to 3.7 mm. All significant differences were noted at p <
      0.05 and p < 0.01. The following suggestions are made based on these results. 1)
      More care should be taken when a transpedicular screw is placed in the horizontal
      plane. 2) Improper medial placement of the pedicle screw, especially in the
      middle thoracic spine, should be avoided, and the anatomic variations between
      individuals should be considered. 3) Because of substantial variations in the
      size of thoracic pedicles, utmost attention should be given to the findings of a
      computed tomographic evaluation before thoracic transpedicular fixation is begun.

PMID- 11242274
TI  - Surgical treatment of adolescent idiopathic scoliosis: a comparative study of two
      segmental instrumentation systems.
AB  - This study compares two different surgical techniques and instrumentation types
      in the treatment of adolescent idiopathic scoliosis. The charts and radiographs
      of 116 patients with adolescent idiopathic scoliosis treated by posterior spine
      fusion with Isola or Cotrel-Dubousset instrumentation were reviewed. Patients
      were separated into two equivalent groups matched for age, sex, curve type, and
      curve magnitude. All patients had a minimum of 2 years follow-up. The
      instrumentation in group 1 consisted of hooks, wires, and pedicle screws. That
      used in group 2 was limited to hooks and rods. The Mann-Whitney, Wilcoxin, and
      the paired Student t tests for matched pairs were used for statistical analysis.
      Patients in group 1 had increased curve correction (66% vs. 52%), apical
      vertebral translation (63% vs. 30%), and correction of the end vertebral tilt
      angle (11 degrees vs. 3 degrees) (p < 0.001). The percentage of coronal curve
      correction in curves larger than 65 degrees also was greater in group 1 (59% vs.
      40%). Physiologic sagittal alignment was obtained in 80% of the patients in group
      1 and 25% in group 2. No major complication or pseudoarthrosis occurred in either
      group. This study supports improved correction of curve magnitude, apical
      translation, and end vertebral tilt angle with the use of multiple anchor types
      compared with the correction achieved with standard hook-and-rod constructs.

PMID- 11242275
TI  - Anterior and posterior allografts in symptomatic thoracolumbar deformity.
AB  - The radiographic and clinical results of 105 patients with symptomatic spinal
      deformities were categorized retrospectively based on surgical approach and type
      of bone autograft or allograft used for each patient's fusion surgery into seven
      different groups and compared with one another. The three bone autograft control
      groups were posterior autograft only (n = 20), anterior autograft only (n = 6),
      and combined anterior and posterior autograft (n = 12). The allograft groups were
      posterior morcellized allograft (n = 7), posterior morcellized allograft and
      anterior autograft (n = 11), anterior structural interbody allografts and
      posterior mixture of allograft and autograft (n = 37), and anterior strut
      allograft with posterior mixture of allograft and autograft (n = 12). Radiographs
      revealed high pseudoarthrosis rates for adults with a posterior-only allograft
      and with anterior strut allografts spanning four or more levels. Results of the
      self-assessment outcomes questionnaire, at a mean follow-up period of 52 months,
      revealed less pain and improved cosmesis for all groups, and improved function in
      patients who had undergone combined anteroposterior fusion. The authors conclude
      that posterior cancellous allograft is a poor substitute for autograft bone and
      that strut allografts spanning more than four levels require technique
      modifications to enhance their effectiveness. In general, anterior structural
      allografts are effective in maintaining correction, result in fusion rates
      comparable to those of autografts, and correlate to improved outcomes.

PMID- 11242276
TI  - Prediction of thoracic kyphosis using the Debrunner kyphometer.
AB  - The Debrunner kyphometer is an accepted tool for detecting and evaluating
      thoracic kyphosis. This prospective study was conducted to create a mathematical
      formula that provides, with high approximation, the roentgenographic angle of
      thoracic kyphosis (T4-T12) using only the kyphometer. Several clinical
      (kyphometer value, age, and sex) and radiographic (Cobb angle [T4-T12])
      parameters from 90 consecutively screened adolescents (44 male and 46 female)
      were correlated using simple and multiple linear regression analyses. The
      reliability of measurement using the Debrunner kyphometer was high. The
      kyphometer value was strongly correlated with the roentgenographically measured
      thoracic Cobb angle (simple linear regression analysis; probability range, 0.0026
      to 0.0002). There was no correlation between age or sex and thoracic kyphosis.
      The predicted kyphosis angle using the kyphometer and the mathematic formula was
      44.66 degrees +/- 2.68 degrees, (range 27 to 62 degrees), and the real
      roentgenographic kyphosis angle was 47.5 degrees +/- 3.53 degrees, (range, 24 to
      70 degrees). The kyphometer and formula were more reliable and accurate when
      kyphosis less than 50 degrees was measured. In this study, the authors
      constructed a mathematical formula that accurately provides the roentgenographic
      T4-T12 kyphosis angle in adolescents using only the Debrunner kyphometer with a
      deviation of less than 3 degrees. The authors recommend that all physicians
      engaged in kyphosis screening programs use the kyphometer combined with the
      recently constructed simple mathematic formula. This method will reduce the cost
      of school screening programs, overdiagnoses, and unnecessary exposure of
      adolescents to irradiation.

PMID- 11242277
TI  - Sterile, benign radiculitis associated with lumbosacral lateral recess spinal
      canal stenosis: evaluation with enhanced magnetic resonance imaging.
AB  - Two cases of symptomatic lumbar lateral recess stenosis are described in which
      the compressed nerve root became focally enhanced on magnetic resonance imaging
      (MRI) studies performed with gadolinium DTPA. Two men with low back pain and
      lumbar radiculopathy were examined with contrast-enhanced MRI studies, which
      showed intradural enhancement of the symptomatic nerve roots. In selected cases
      of lateral recess stenosis, focal radicular injury may be visualized on enhanced
      MRI as a result of a breakdown of the blood-brain barrier.

PMID- 11242278
TI  - Spinal epidural gas after cardiac surgery.
AB  - The authors describe a patient with severe lower back and left leg pain in the
      early postoperative period after cardiac surgery. Radiologic examination revealed
      gas in the spinal epidural space at the level of L4-5. The pain could not be
      relieved with analgesics and the patient underwent lumber surgery after cardiac
      surgery. After decompression, the patient improved and was discharged with no
      symptoms.

PMID- 11242279
TI  - Transclavicular approach for a large dumbbell tumor in the cervicothoracic
      junction.
AB  - Neurogenic dumbbell tumors occur more frequently in the cervical than in the
      thoracic or lumbar spine. Cervical paravertebral masses usually do not become
      exceptionally large because they are superficial and are palpated easily.
      Thoracic tumors can become large before they are detected. The authors describe a
      large intrathoracic dumbbell tumor arising from the C8 nerve root. The
      intraspinal tumor was resected through a posterior approach. In the second stage,
      dividing the clavicle, the intrathoracic component was resected by separating it
      from the lung. Two years after treatment, the preoperative neurologic deficit had
      improved except for weakness of muscles innervated by the C8 nerve root.
      Radiographs showed no residual or recurrent mass at the apex of the lung.
      Sometimes a retroclavicular location may conceal a large paravertebral mass, such
      as Pancoast tumors. As described here, the transclavicular approach gave adequate
      access to the cervicothoracic junction.

PMID- 11242280
TI  - Exuberant transverse ligament degeneration causing high cervical myelopathy.
AB  - Two patients with cervical myelopathy and C1-C2 retro-odontoid masses were
      examined. Preoperative magnetic resonance imaging studies suggested soft tissue
      pannus, as might be seen in rheumatoid arthritis; however, the results of
      serologic testing for rheumatoid factor were negative in both patients.
      Intraoperative findings and pathologic examination revealed degenerative
      fibrocartilage without inflammation or neoplasia. Similar lesions reported in the
      literature have been described as retro-odontoid disk hernia, damaged transverse
      ligaments, transverse ligament degeneration, synovial cysts, ganglion cysts, and
      degenerative articular cysts. These lesions may share a common pathophysiologic
      origin and represent a single disease process, namely exuberant degeneration of
      the transverse ligament.

PMID- 11242281
TI  - Validation of the American Association for the Surgery of Trauma organ injury
      severity scale for the kidney.
AB  - BACKGROUND: We queried an observational database of renal trauma patients to
      validate the organ injury severity scale (kidney) of the American Association for
      the Surgery of Trauma (AAST). METHODS: In a retrospective review of our renal
      trauma database (2,467 patients) with 58 clinical and radiographic patient
      variables, statistical "classification trees" were used to determine factors
      predicting need for surgical repair. RESULTS: Scales correlated with the need for
      surgery (grade I = 0%, grade II = 15%, grade III = 76%, grade IV = 78%, and grade
      V = 93%) and for nephrectomy (grade I = 0%, grade II = 0%, grade III = 3%, grade
      IV = 9%, and grade V = 86%). Classification tree analysis (confirmed in 83
      additional patients) identified the AAST organ injury severity scale as the most
      important variable predicting the need for renal repair. CONCLUSION: In a
      retrospective review of more than 2,500 patients, we determined that the AAST
      organ injury severity scale correlates with the need for kidney repair or
      removal. Classification tree analysis confirmed the scale as the prime variable
      predicting need for surgical repair.

PMID- 11242282
TI  - Prospective evaluation of thoracic ultrasound in the detection of pneumothorax.
AB  - BACKGROUND: Thoracic ultrasound may rapidly diagnose pneumothorax when
      radiographs are unobtainable; the accuracy is not known. METHODS: We
      prospectively evaluated thoracic ultrasound detection of pneumothorax in patients
      at high suspicion of pneumothorax. The presence of "lung sliding" or "comet tail"
      artifacts were determined in patients by ultrasound before radiologic
      verification of pneumothorax by residents instructed in thoracic ultrasound.
      Results were compared with standard radiography. RESULTS: There were 382 patients
      enrolled; the cause of injury was blunt (281 of 382), gunshot wound (22 of 382),
      stab wound (61 of 382), and spontaneous (18 of 382). Pneumothorax was
      demonstrated on chest radiograph in 39 patients and confirmed by ultrasound in 37
      of 39 patients (95% sensitivity); two pneumothoraces could not be diagnosed
      because of subcutaneous air; the true-negative rate was 100%. CONCLUSION:
      Thoracic ultrasound reliably diagnoses pneumothorax. Expansion of the focused
      abdominal sonography for trauma (FAST) examination to include the thorax should
      be investigated for terrestrial and space medical applications.

PMID- 11242283
TI  - Hypertonic saline alteration of the PMN cytoskeleton: implications for signal
      transduction and the cytotoxic response.
AB  - BACKGROUND: Recognition that hypertonic saline (HTS) modulates the inflammatory
      response has renewed interest in this agent for postinjury resuscitation. Changes
      in extracellular tonicity alter cell shape and are accompanied by cytoskeletal
      reorganization. Recent evidence suggests that cytoskeletal reorganization is
      critical for receptor-mediated signal transduction. We hypothesized that HTS
      induced changes in the cytoskeleton interfere with cytotoxic signal transduction.
      METHODS: Isolated neutrophils (PMNs) were incubated in HTS (Na+ = 180 mmol/L) and
      activated with N-formyl-methionyl-leucyl-phenylalanine (receptor-mediated) or
      phorbol myristate (receptor independent). Actin polymerization was assessed by
      digital image microscopy and flow cytometry. PMN superoxide anion (O2-)
      production and p38 MAPK activation was measured by reduction of cytochrome c and
      Western blot. Pretreatment with cytochalasin B was used to disrupt HTS-induced
      actin reorganization. RESULTS: HTS inhibited receptor-mediated cytoskeletal
      reorganization and attenuated p38 MAPK activation and O2- production. HTS had no
      effect on receptor-independent O2- production. Cytoskeletal disruption
      (cytochalasin B) prevented HTS attenuation of receptor-mediated p38 MAPK
      activation. CONCLUSION: HTS attenuates the PMN cytotoxic response by interfering
      with intracellular signal transduction. Changes in the actin cytoskeleton appear
      to modulate receptor-mediated p38 MAPK signaling.

PMID- 11242284
TI  - Thrombin-mediated permeability of human microvascular pulmonary endothelial cells
      is calcium dependent.
AB  - BACKGROUND: In response to inflammation, endothelial cytoskeleton rearrangement,
      cell contraction, and intercellular gap formation contribute to a loss of
      capillary barrier integrity and resultant interstitial edema formation. The
      intracellular signals controlling these events are thought to be dependent on
      intracellular calcium concentration ([Ca2+]i). We hypothesized that, in human
      pulmonary microvascular endothelial cells, a thrombin-induced increase in
      permeability to albumin would be dependent on Ca2+i and subsequent actin
      cytoskeleton rearrangements. METHODS: Human lung microvascular endothelial cells,
      grown on 0.4 micromol/L pore membranes, were activated with 10 nmol/L human
      thrombin in Hank's balanced salt solution/0.5% fetal bovine serum. Select
      cultures were pretreated (45 minutes) with 4 micromol Fura-2/AM to chelate Ca2+i.
      Permeability was assessed as diffusion of bovine serum albumin/biotin across the
      monolayer. Similarly treated cells were stained with rhodamine-phalloidin to
      demonstrate actin cytoskeletal morphology. Separately, cells loaded 2 micromol
      Fura-2/AM were assessed at OD340/380nm after thrombin exposure to detect free
      Ca2+i. RESULTS: Intracellular Ca2+ levels increased 15-fold (2 seconds) and fell
      to baseline (10 minutes) after thrombin. Permeability increased 10-fold (30
      minutes), and a shift from cortical to actin stress fiber morphology was
      observed. Chelation of Ca2+i diminished permeability to baseline and reduced the
      percentage of cells exhibiting stress fiber formation. CONCLUSION: Thrombin
      stimulates pulmonary capillary leak by affecting the barrier function of
      activated pulmonary endothelial cells. These data demonstrate a thrombin
      stimulated increase in monolayer permeability, and cytoskeletal F-actin stress
      fibers were, in part, regulated by endothelial Ca2+i. This early, transient rise
      in Ca2+i likely activates downstream pathways that more directly affect the
      intracellular endothelial structural changes that control vascular integrity.

PMID- 11242285
TI  - Endovascular stent grafting for the treatment of blunt thoracic aortic injury.
AB  - OBJECTIVE: Recent advances of endovascular stent-grafting (ESG) provide a new
      therapeutic option with minimum surgical damage for blunt aortic injury (BAI)
      during its acute phase. To clarify the effectiveness of ESG for BAI, a
      prospective clinical study at a university hospital was conducted. METHODS: All
      patients with blunt thoracic injury underwent thoracic contrast-enhanced computed
      tomographic (CT) scan. Six patients age 48.8 +/- 19.8 years, with Injury Severity
      Scores of 35.8 +/- 8.1, and with BAI were treated according to our protocol. The
      stent-graft covered by woven Dacron was placed at the injury site. Endoleakage
      was then checked by aortography and CT scan was again performed once a day on
      days 7 through 14. RESULTS: All patients had injury of the aortic isthmus. ESG
      placement was performed within 8 hours after injury except in one (48 hours). The
      operating time was 159.5 +/- 21.1 minutes and bleeding volume was 105 +/- 26.6
      mL. No endoleakage was found. Repeat CT scan revealed disappearance of hematoma.
      All patients except one had an event-free clinical course. One patient died
      because of rupture of the ascending aorta on day 6; however, autopsy revealed
      evidence of the healing process at the injury site sealed by ESG. CONCLUSION: An
      ESG is a valid therapeutic option with minimal surgical invasion for patients
      with acute-phase aortic injury.

PMID- 11242286
TI  - Failures of splenic nonoperative management: is the glass half empty or half
      full?
AB  - BACKGROUND: Published contraindications to nonoperative management (NOM) of blunt
      splenic injury (BSI) include age > or = 55, Glasgow Coma Scale score < or = 13,
      admission blood pressure < 100 mm Hg, major (grades 3-5) injuries, and large
      amounts of hemoperitoneum. Recently reported NOM rates approximate 60%, with
      failure rates of 10% to 15%. This study evaluated our failures of NOM for BSI
      relative to these clinical factors. METHODS: All patients with BSI at a Level I
      trauma center over a 46-month period ending September 1999 were reviewed.
      Failures of NOM included patients initially selected for NOM who subsequently
      required splenectomy/splenorrhaphy. RESULTS: Five hundred fifty-eight had BSI.
      Twenty-three percent (128) underwent emergent laparotomy for hemodynamic
      instability and 77% (430) were observed. The NOM failure rate was only 8%.
      Univariate analysis identified moderate to large hemoperitoneum (p < 0.03),
      grades 3 to 5 (p < 0.004), and age > or = 55 (p < 0.0006) as being significantly
      associated with failure. Multivariate analysis identified age > or = 55 and
      grades 3 to 5 injuries as independent predictors of failure. The highest failure
      rates (30-40%) occurred in patients age > or = 55 with major injury for moderate
      to large hemoperitoneum. Mortality rates for successful NOM were 12%, and 9% for
      failed NOM. CONCLUSION: Inclusion of all high-risk patients increased the NOM
      rate while maintaining a low failure rate. Although age > or = 55 and major BSI
      were independently associated with failure of NOM, approximately 80% of these
      high-risk patients were successfully managed nonoperatively. There was no
      increased mortality associated with failure. Although these factors may indeed
      predict failure, they do not necessarily contraindicate NOM.

PMID- 11242287
TI  - Clinically significant blunt cardiac trauma: role of serum troponin levels
      combined with electrocardiographic findings.
AB  - BACKGROUND: The true importance of blunt cardiac trauma (BCT) is related to the
      cardiac complications arising from it. Diagnostic tests that can predict
      accurately if such complications will develop or not may allow early and
      aggressive monitoring or early discharge. We investigated the role of two simple
      and convenient tests, serum cardiac troponin I (cTnI) and electrocardiogram
      (ECG), when used to identify patients at risk of cardiac complications after BCT.
      METHODS: Over a 10-month period, 115 patients with evidence of significant blunt
      thoracic trauma were prospectively followed to identify the presence of
      clinically significant BCT (Sig-BCT), defined as cardiogenic shock, arrhythmias
      requiring treatment, or structural cardiac abnormalities directly related to the
      cardiac trauma. An ECG was obtained at admission and at 8 hours. Cardiac troponin
      I was measured at admission, at 4 hours, and at 8 hours. Transthoracic
      echocardiography was performed when clinically indicated. The sensitivity,
      specificity, and positive and negative predictive values of ECG and cTnI to
      identify Sig-BCT were calculated. Clinical risk factors for Sig-BCT were examined
      by univariate and multivariate analysis. RESULTS: Nineteen patients (16.5%) were
      diagnosed with Sig-BCT and, in 18 of them, symptoms presented within 24 hours of
      admission. Abnormal electrocardiographic findings were detected in 58 patients
      (50%) and elevated cTnI levels in 27 (23.5%). Electrocardiography and cTnI had
      positive predictive values of 28% and 48% and negative predictive values of 95%
      and 93%, respectively. However, when both tests were abnormal (positive) or
      normal (negative), the positive and negative predictive values increased to 62%
      and 100%, respectively. Other independent risk factors for Sig-BCT were head
      injury, spinal injury, history of preexisting cardiac disease, and a chest
      Abbreviated Injury Score greater than 2. CONCLUSION: The combination of ECG and
      cTnI identifies reliably the presence or absence of Sig-BCT. Patients with an
      abnormal ECG and cTnI need close monitoring for at least 24 hours. Patients with
      a normal admission ECG and cTnI can be safely discharged in the absence of other
      injuries.

PMID- 11242288
TI  - Laparotomy potentiates cytokine release and impairs pulmonary function after
      hemorrhage and resuscitation in mice.
AB  - BACKGROUND: The two-hit theory has emerged as a mechanism to explain the
      development of organ failure after traumatic injury. We evaluated the effects of
      exploratory laparotomy (EL) as a second hit on mice after hemorrhage and
      resuscitation (H/R). Our hypothesis was that mice exposed to prior H/R would
      demonstrate more evidence of acute lung injury (ALI), as well as an augmented
      cytokine response, than mice exposed to H/R or EL alone. METHODS: Three groups of
      mice were examined. Mice undergoing H/R alone were labeled as the H/R group. Mice
      undergoing sham H/R (cannulation but no hemorrhage), followed 5 days later by EL,
      were labeled as the EL group; and mice undergoing H/R, followed 5 days later by
      an EL, were labeled as the H/R + EL, or two-hit, group. Respiratory function was
      determined by using whole-body plethysmography and lung gas diffusion. Serum
      interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were assayed at
      1 and 4 hours after the injury stimuli. RESULTS: Evaluation of the change in
      pulmonary function after 24 hours demonstrated that EL alone induces a
      significant decrease in pulmonary function, whereas two-hit mice did not exhibit
      a potentiated response. Alveolar function was significantly degraded in the EL
      group compared with all other groups (p < 0.0001). TNF-alpha did not change after
      any injury at any time. However, evaluation of IL-6 levels demonstrated a
      substantial increase after H/R, EL, and H/R + EL compared with baseline and at 1
      hour. Comparison of the three groups at 4 hours did not demonstrate any
      differences in serum concentrations of IL-6. Histologic evaluation lungs
      demonstrated that the most severe lung injury was seen in the EL mice.
      CONCLUSION: It would appear that serum TNF-alpha has little impact on the
      pathogenesis of ALI after EL, whereas serum IL-6 may be more important.
      Exploratory laparotomy resulted in a significant change in pulmonary function.
      Contrary to our initial hypothesis, two-hit mice did not demonstrate more
      evidence of ALI and, in fact, demonstrated less lung injury than EL mice.

PMID- 11242289
TI  - Mild hypothermia increases survival from severe pressure-controlled hemorrhagic
      shock in rats.
AB  - BACKGROUND: In previous studies, mild hypothermia (34 degrees C) during
      uncontrolled hemorrhagic shock (HS) increased survival. Hypothermia also
      increased mean arterial pressure (MAP), which may have contributed to its
      beneficial effect. We hypothesized that hypothermia would improve survival in a
      pressure-controlled HS model and that prolonged hypothermia would further improve
      survival. METHODS: Thirty rats were prepared under light nitrous oxide/halothane
      anesthesia with spontaneous breathing. The rats underwent HS with an initial
      blood withdrawal of 2 mL/100 g over 10 minutes and pressure-controlled HS at a
      MAP of 40 mm Hg over 90 minutes (without anticoagulation), followed by return of
      shed blood and additional lactated Ringer's solution to achieve normotension.
      Hemodynamic monitoring and anesthesia were continued to 1 hour, temperature
      control to 12 hours, and observation without anesthesia to 72 hours. After HS of
      15 minutes, 10 rats each were randomized to group 1, with normothermia (38
      degrees C) throughout; group 2, with brief mild hypothermia (34 degrees C during
      HS 15-90 minutes plus 30 minutes after reperfusion); and group 3, with prolonged
      mild hypothermia (same as group 2, then 35 degrees C [possible without shivering]
      from 30 minutes after reperfusion to 12 hours). RESULTS: MAP during HS and
      initial resuscitation was the same in all three groups, but was higher in the
      hypothermia groups 2 and 3, compared with the normothermia group 1, at 45 and 60
      minutes after reperfusion. Group 1 required less blood withdrawal to maintain MAP
      40 mm Hg during HS and more lactated Ringer's solution for resuscitation. At end
      of HS, lactate levels were higher in group 1 than in groups 2 and 3 (p < 0.02).
      Temperatures were according to protocol. Survival to 72 hours was achieved in
      group 1 by 3 of 10 rats, in group 2 by 7 of 10 rats (p = 0.18 vs. group 1), and
      in group 3 by 9 of 10 rats (p = 0.02 vs. group 1, p = 0.58 vs. group 2). Survival
      time was longer in group 2 (p = 0.09) and group 3 (p = 0.007) compared with group
      1. CONCLUSION: Brief hypothermia had physiologic benefit and a trend toward
      improved survival. Prolonged mild hypothermia significantly increased survival
      after severe HS even with controlled MAP. Extending the duration of hypothermia
      beyond the acute phases of shock and resuscitation may be needed to ensure
      improved outcome after prolonged HS.

PMID- 11242290
TI  - Assessment of tissue viability in complex extremity injuries: utility of the
      pyrophosphate nuclear scan.
AB  - BACKGROUND: Extensive extremity injuries often require difficult decisions
      regarding the necessity for amputation or radical debridement. During the past
      decade, we have used technetium-99 pyrophosphate (PyP) scanning as an adjunct in
      this setting. This study was performed to assess the accuracy of PyP scan in
      predicting the need for amputation in relation to clinical, operative, and
      pathologic findings. METHODS: Review of our computerized registry identified 11
      patients (10 men, age 36.1 +/- 14.9 years) admitted from 1990 to 1999 who
      underwent PyP scan. Using operative and pathologic findings, accuracy of the PyP
      scan was graded as supporting or refuting the clinical assessment of the need for
      amputation. RESULTS: Eight patients suffered high-voltage electrical injuries,
      one had severe frostbite, and two suffered soft-tissue infections. In most cases,
      PyP scan showed clear demarcation of viable and nonviable tissue, verifying the
      need for amputation (positive); those that demonstrated viable distal tissues
      confirmed at operation were considered negative. PyP scan had a sensitivity of
      94%, a specificity of 100%, and an accuracy of 96% in this setting. CONCLUSION:
      Technetium-99 PyP scanning is a useful adjunct in predicting the need for
      amputation in extremities damaged by electrical injury, frostbite, or invasive
      infection. In addition, by providing an objective "picture" of extremity
      perfusion, PyP scans can be helpful in convincing patients of the need for
      amputation.

PMID- 11242291
TI  - The importance of gender on outcome after major trauma: functional and
      psychologic outcomes in women versus men.
AB  - BACKGROUND: Outcome after major trauma is an increasingly important focus of
      injury research. The effect of gender on functional and psychological outcomes
      has not been examined. The Trauma Recovery Project is a large, prospective,
      epidemiologic study designed to examine multiple outcomes after major trauma,
      including quality of life, functional outcome, and psychological sequelae such as
      depression and early symptoms of acute stress reaction. The specific objectives
      of the present report are to examine gender differences in short- and long-term
      functional and psychological outcomes in the Trauma Recovery Project population.
      METHODS: Between December 1, 1993, and September 1, 1996, 1,048 eligible trauma
      patients triaged to four participating trauma center hospitals in the San Diego
      Regionalized Trauma System were enrolled in the study. The enrollment criteria
      for the study included age 18 years and older, admission Glasgow Coma Scale score
      of 12 or greater, and length of stay greater than 24 hours. Quality of life was
      measured after injury using the Quality of Well-being scale, a sensitive index to
      the well end of the functioning continuum (range, 0 = death to 1.000 = optimum
      functioning). Depression was assessed using the Center for Epidemiologic Studies
      Depression scale and early symptoms of acute stress reaction were assessed using
      the Impact of Events scale. Patient outcomes were assessed at discharge and at 6,
      12, and 18 months after discharge. RESULTS: Functional outcome was significantly
      worse at each follow-up time point in women (n = 313) versus men (n = 735).
      Quality of Well-being scale scores were markedly and significantly lower at 6
      month follow-up in women compared with those in men (0.606 vs. 0.646, p <
      0.0001). This association persisted at 12-month (0.637 vs. 0.6685, p < 0.0001)
      and 18-month (0.646 vs. 0.6696, p < 0.0001) follow-up. Women were also
      significantly more likely to be depressed at all follow-up time points (discharge
      odds ratio [OR] = 1.4, p < 0.05; 6-month follow-up OR = 2.2, p < 0.01; 12-month
      follow-up OR = 2.0, p < 0.01; 18-month follow-up OR = 2.2, p < 0.01) and to have
      early symptoms of acute stress reaction at discharge (OR = 1.4, p < 0.05). These
      differences remained significant and independent after adjusting for injury
      severity, mechanism, age, and sociodemographic factors. CONCLUSION: Women are at
      risk for markedly worse functional and psychological outcomes after major trauma
      than men, independent of injury severity and mechanism. Gender differences in
      short- and long-term trauma outcomes have important implications for future
      studies of recovery from trauma.

PMID- 11242292
TI  - Gender differences in adverse outcomes after blunt trauma.
AB  - BACKGROUND: High testosterone and low estradiol levels induce immunosuppression
      and adverse outcome after trauma in male animals. Gender-based outcome
      differences in human trauma have not been investigated. In order to test our
      hypothesis that female gender is associated with improved outcome after trauma,
      we conducted an inception cohort study at the R. Adams Cowley Shock Trauma
      Center, the adult trauma resource center for the state of Maryland. METHODS: All
      were blunt trauma patients (18,892) admitted from 1983 to 1995, stratified by
      Injury Severity Score (ISS) and age. Gender differences in mortality; nosocomial
      infection; and preinjury diabetes and cardiac, pulmonary, and liver diseases were
      determined. RESULTS: No significant differences in preinjury diseases were
      identified. Death and gender were independent variables in all groups except for
      patients who developed pneumonia. Male patients had a higher incidence of
      pneumonia in all groups except age 18 to 45, with an ISS < 15. The association
      between male gender and pneumonia was strongest in the age 46 to 65, ISS > 30
      subgroup (p < 0.01). Among those with pneumonia, female patients were at 2.8 to
      5.6 times higher risk for death than were male patients. CONCLUSION: These data
      suggest that gender has no relation to mortality in blunt trauma patients who do
      not develop pneumonia. In contrast, male gender was significantly associated with
      an increased incidence of pneumonia after injury, and female patients with
      pneumonia were at significantly higher risk for mortality.

PMID- 11242293
TI  - Female compared with male fatality risk from similar physical impacts.
AB  - OBJECTIVE: If a female and a male suffer similar potentially lethal physical
      impacts, which of them (other factors being equal) is more likely to die? This
      question is addressed using 245,836 traffic fatalities. METHODS: Fatality risk
      ratios were estimated using crash data for cars, light trucks, and motorcycles
      with two occupants, at least one being killed. Combinations of seat belt use,
      helmet use, and seating location led to 14 occupant categories. RESULTS:
      Relationships between fatality risk and gender are similar for all 14 occupant
      categories. Female fatality risk exceeds male risk from preteens to late 50s. For
      ages from about 20 to about 35, female risk exceeds male risk by (28 +/- 3)%.
      CONCLUSION: Whereas specific injury mechanisms differ greatly between the 14
      occupant categories, the effect of gender on fatality risk does not, thus
      implying that the relationships reflect fundamental gender-dependent differences.

PMID- 11242296
TI  - Treatment of diaphyseal forearm fractures in children by intramedullary Kirschner
      wires.
AB  - BACKGROUND: This article presents a retrospective analysis of a case series of
      diaphyseal forearm fractures in children treated with intramedullary Kirschner
      wires (K-wires). METHODS: Seventy-four diaphyseal forearm fractures in children
      (63 male subjects and 11 female subjects) with a mean age of 11 years (range, 4
      15 years) were treated with percutaneous intramedullary K-wires. Under
      fluoroscopic control, a standard K-wire (diameter, 1.5-2.0 mm, depending on the
      age) was introduced into the distal radial metaphysis, proximal to the epiphysis.
      The K-wire was then advanced proximally across the fracture. For the ulna, the
      wire was introduced antegrade from the proximal end. The tip of the K-wire was
      prebent to 30 degrees to facilitate closed reduction of the displaced fracture.
      RESULTS: All fractures healed between 6 and 10 weeks with minimum complications
      and excellent clinical results. CONCLUSION: This surgical technique is
      convenient, effective, and safe for treating displaced diaphyseal forearm
      fractures in children.

PMID- 11242295
TI  - Estimation of intra-abdominal pressure by bladder pressure measurement: validity
      and methodology.
AB  - BACKGROUND: Increased intra-abdominal pressure (IAP) is an adverse complication
      seen in critically ill, injured, and postoperative patients. IAP is estimated via
      the measurement of bladder pressure. Few studies have been performed to establish
      the actual relationship between IAP and bladder pressure. The purpose of this
      study was to confirm the association between intravesicular pressure and IAP and
      to determine the bladder volume that best approximates IAP. METHODS: Thirty-seven
      patients undergoing laparoscopy had intravesicular pressures measured with
      bladder volumes of 0, 50, 100, 150, and 200 mL at directly measured intra
      abdominal pressures of 0, 5, 10, 15, 20, and 25 mm Hg. Correlation coefficients
      and differences were then determined. RESULTS: Across the IAP range of 0 to 25 mm
      Hg using all of the tested bladder volumes, the difference between IAP and
      intravesicular pressures (bias) was -3.8 +/- 0.29 mm Hg (95% confidence interval)
      and measurements were well correlated (R2 = 0.68). Assessing all IAPs tested, a
      bladder volume of 0 mL demonstrated the lowest bias (-0.79 +/- 0.73 mm Hg). When
      considering only elevated IAPs (25 mm Hg), a bladder volume of 50 mL revealed the
      lowest bias (-1.5 +/- 1.36 mm Hg). A bladder volume of 50 mL in patients with
      elevated IAP resulted in an intravesicular pressure 1 to 3 mm Hg higher than IAP
      (95% confidence interval). CONCLUSION: Intravesicular pressure closely
      approximates IAP. Instillation of 50 mL of liquid into the bladder improves the
      accuracy of the intravesicular pressure in measuring elevated IAPs.

PMID- 11242294
TI  - Penetrating esophageal injuries: multicenter study of the American Association
      for the Surgery of Trauma.
AB  - OBJECTIVE: The purpose of this study was to define the period of time after which
      delays in management incurred by investigations cause increased morbidity and
      mortality. The outcome study is intended to correlate time with death from
      esophageal causes, overall complications, esophageal related complications, and
      surgical intensive care unit length of stay. METHODS: This was a retrospective
      multicenter study involving 34 trauma centers in the United States, under the
      auspices of the American Association for the Surgery of Trauma Multi
      institutional Trials Committee over a span of 10.5 years. Patients surviving to
      reach the operating room (OR) were divided into two groups: those that underwent
      diagnostic studies to identify their injuries (preoperative evaluation group) and
      those that went immediately to the OR (no preoperative evaluation group).
      Statistical methods included Fisher's exact test, Student's T test, and logistic
      regression analysis. RESULTS: The study involved 405 patients: 355 male patients
      (86.5%) and 50 female patients (13.5%). The mean Revised Trauma Score was 6.3,
      the mean Injury Severity Score was 28, and the mean time interval to the OR was
      6.5 hours. There were associated injuries in 356 patients (88%), and an overall
      complication rate of 53.5%. Overall mortality was 78 of 405 (19%). Three hundred
      forty-six patients survived to reach the OR: 171 in the preoperative evaluation
      group and 175 in the no preoperative evaluation group. No statistically
      significant differences were noted in the two groups in the following parameters:
      number of patients, age, Injury Severity Score, admission blood pressure,
      anatomic location of injury (cervical or thoracic), surgical management (primary
      repair, resection and anastomosis, resection and diversion, flaps), number of
      associated injuries, and mortality. Average length of time to the OR was 13 hours
      in the preoperative evaluation group versus 1 hour in the no preoperative
      evaluation group (p < 0.001). Overall complications occurred in 134 in the
      preoperative evaluation group versus 87 in the no preoperative evaluation group
      (p < 0.001), and 74 (41%) esophageal related complications occurred in the
      preoperative evaluation group versus 32 (19%) in the no preoperative evaluation
      group (p = 0.003). Mean surgical intensive care unit length of stay was 11 days
      in the preoperative evaluation group versus 7 days in the no preoperative
      evaluation group (p = 0.012). Logistic regression analysis identified as
      independent risk factors for the development of esophageal related complications
      included time delays in preoperative evaluation (odds ratio, 3.13), American
      Association for the Surgery of Trauma Organ Injury Scale grade >2 (odds ratio,
      2.62), and resection and diversion (odds ratio, 4.47). CONCLUSION: Esophageal
      injuries carry a high morbidity and mortality. Increased esophageal related
      morbidity occurs with the diagnostic workup and its inherent delay in operative
      repair of these injuries. For centers practicing selective management of
      penetrating neck injuries and transmediastinal gunshot wounds, rapid diagnosis
      and definitive repair should be made a high priority.

PMID- 11242297
TI  - Artificial neural network predicts CT scan abnormalities in pediatric patients
      with closed head injury.
AB  - BACKGROUND: Artificial neural networks (ANNs) use nonlinear statistical modeling
      techniques to explore relationships in complex clinical situations. This study
      compared predictive ability of a trained ANN model to that of physician
      prediction of cranial computed tomographic (CT) scan abnormalities in children
      with head injury. METHODS: A prospective cohort of 351 patients who presented
      with head trauma and underwent CT scans were studied. All pertinent data on
      historical and demographic information, and clinical features were recorded.
      Emergency department physicians used clinical judgment to record pretest
      probability of abnormal CT scans for all patients prospectively. Similar data
      from a retrospective chart review of 382 patients with head injury in the
      immediate preceding year were collected and used to train the ANN. Data from the
      prospective study was used to validate the ANN, construct a logistic regression
      model, and compare physician prediction. RESULTS: Forty-five (12.9%) of 351
      patients had abnormal CT scans. In predicting CT scan abnormality, the ANN model
      was more sensitive (82.2%) compared with physician prediction (62.2%).
      CONCLUSION: ANNs may serve as a useful aid for decision support for emergency
      physicians in predicting intracranial abnormalities in closed head injury.

PMID- 11242298
TI  - Drugs and traffic crash responsibility: a study of injured motorists in Colorado.
AB  - BACKGROUND: Alcohol is a contributing factor in a large proportion of traffic
      crashes. However, the role of other drugs is unknown. The objectives of this
      study are to determine the prevalence of recent drug use among drivers injured in
      traffic crashes, and to determine the extent to which drugs are responsible for
      crashes. METHODS: We studied 414 injured drivers who presented to an urban
      emergency department within 1 hour of their crash. Demographic and injury data
      were collected from medical records. Urine toxicologic assays were conducted for
      legal and illegal drugs. Traffic crash reports were analyzed for crash
      responsibility by a trained crash reconstructionist. The causal role of drugs in
      traffic crashes was measured by comparing drug assay results in drivers judged
      responsible for their crashes (cases) and those not responsible (controls). Odds
      ratios and 95% confidence intervals (CIs) were calculated. RESULTS: Thirty-two
      percent (95% CI = 27-37) of the urine samples were positive for at least one
      potentially impairing drug. Marijuana was detected most frequently (17%),
      surpassing alcohol (14%). Compared with drug- and alcohol-free drivers, the odds
      of crash responsibility were higher in drivers testing positive for alcohol alone
      (odds radio [OR] = 3.2, 95% CI = 1.1-9.4) and in drivers testing positive for
      alcohol in combination with other drugs (OR = 3.5, 95% CI = 1.2-11.4). Marijuana
      alone was not associated with crash responsibility (OR = 1.1, 95% CI = 0.5-2.4).
      In a multivariate analysis, controlling for age, gender, seat belt use, and other
      confounding variables, only alcohol predicted crash responsibility. CONCLUSION:
      Alcohol remains the dominant drug associated with injury-producing traffic
      crashes. Marijuana is often detected, but in the absence of alcohol, it is not
      associated with crash responsibility.

PMID- 11242299
TI  - Interferon-gamma modifies cytokine release in vitro by monocytes from surgical
      patients.
AB  - BACKGROUND: Treatment with interferon-gamma (IFN-gamma), a key mediator for
      adequate forward-regulatory monocyte immune capability, has been advocated to
      overcome posttraumatic mononuclear leukocyte paralysis. Conversely, IFN-gamma
      also is a potent proinflammatory mediator contributing to capillary leakage in
      sepsis-driven organ failure. The objective of this investigation was to further
      define the potential of IFN-gamma as a modifier of monocyte activity before and
      after injury. METHODS: Whole blood samples from 19 patients (7 female and 12 male
      patients; age, 68 +/- 5 years) before and after cardiac surgery with
      extracorporeal circulation were incubated under continuous rotation with
      lipopolysaccharide for 12 hours in the presence or absence of human recombinant
      IFN-gamma. Pro- and anti-inflammatory cytokines were determined in the plasma.
      RESULTS: Lipopolysaccharide-induced release of tumor necrosis factor-alpha,
      interleukin (IL)-6, IL-12, and IL-1Ra, and prostaglandin E2 was clearly augmented
      with IFN-gamma most strikingly postoperatively (p < 0.05). There was no effect on
      IL-1beta, neopterin, and soluble tumor necrosis factor-R release. CONCLUSION:
      Thus there is a wide spectrum of IFN-gamma activity on monocyte activation
      including anti-inflammatory properties. Since cellular preactivation facilitates
      monocyte reactivity toward IFN-gamma, we conclude that exogenous administration
      should be effective but must be carried out with great caution in patients with
      profound inflammation.

PMID- 11242300
TI  - Warning from Nagano: increase of vulvar hematoma and/or lacerated injury caused
      by snowboarding.
AB  - BACKGROUND: On the basis of the number of women snowboarders whose vulvar
      injuries we have recently treated, we believe that the cases of vulvar hematoma
      and lacerated injuries caused by snowboarding have been increasing. To analyze
      the causal relation between snowboarding and vulvar injuries, we investigated how
      women were injured during snowboarding. METHODS: During the last three ski-ing
      seasons at the five hospitals near the ski resorts in Nagano Prefecture, Japan,
      the clinical charts of all patients with vulvar injuries during snowboarding were
      reviewed for the number of patients treated, the condition of the patients at
      diagnosis, and the characteristics of vulvar injuries. All patients were also
      asked by phone about how their vulvar injury was caused during snowboarding.
      RESULTS: The number of patients with vulvar injuries during the last three
      seasons was 16, 14, and 35, respectively. The types of vulvar injuries included
      hematoma in 33 (51%) patients, hematoma with lacerated injury in 17 (26%), and
      lacerated injury in the remaining 15 (23%). Of the 65 patients, 45 (69%) needed
      surgical treatment. Characteristically, 54 (88%) patients were injured when they
      tumbled onto the binding of the snowboard at the same time that one foot was left
      off the board and the binding was not turned down but left erect. CONCLUSION: It
      is important for women snowboarders to realize that in snowboarding there are
      dangers that may cause vulvar injuries. The prevention of such injuries requires
      that the binding should be turned down when the foot is left off the board and
      that snowboarders should try not to tumble onto the board.

PMID- 11242301
TI  - Late thoracic outlet syndrome secondary to malunion of the fractured clavicle:
      case report and review of the literature.

PMID- 11242302
TI  - Shoulder restraint injury to the female breast: a crush injury with long-lasting
      consequences.

PMID- 11242303
TI  - Common iliac artery dissection after blunt trauma: case report of endovascular
      repair and literature review.

PMID- 11242304
TI  - Perforation of small intestine inside an internal omphalocele after blunt trauma:
      case report and review of the literature.

PMID- 11242305
TI  - Retained intracranial foreign body (carabiner hook) after inner-tubing accident:
      a novel cause of penetrating head injury and review of inner-tubing injuries.

PMID- 11242306
TI  - Rhino-orbitocerebral mucormycosis attributable to Apophysomyces elegans in an
      immunocompetent individual: case report and review of the literature.

PMID- 11242307
TI  - A new technique to resurface wounds with composite biocompatible epidermal graft
      and artificial skin.
AB  - BACKGROUND: The incorporation of cultured epidermal autograft on the neodermis of
      artificial skin (Integra, Integra LifeSciences, Plainsboro, NJ) has been met with
      some difficulties. A new engraftment technique to resurface the wounds with
      Integra and composite biocompatible epidermal graft (CBEG) has been successfully
      applied on three patients for elective reconstructive procedures. METHODS: A
      small skin biopsy was taken from the normal edge of the lesion for keratinocytes
      and dermal fibroblast cultures 2 weeks before surgery. When sufficient cells were
      grown, the patient was admitted for the excision of the lesions or scars. The
      wounds of the patients, ranging from 125 to 250 cm2, were covered with Integra.
      When the neodermis of the Integra was fully vascularized, the silicone membrane
      of the Integra was removed and replaced with the CBEG, which consisted of
      autologous keratinocytes cultivated on a hyaluronate-derived membrane (Laserskin;
      Fidia Advanced Biopolymers, Abano Terme, Italy)) using human dermal fibroblasts
      as a feeder layer. RESULTS: Clinically, there was good initial "take" of the
      CBEGs in these three patients, ranging from 50% to 100%. Biopsy specimens of the
      grafted wounds were taken 1 to 3 weeks after the application of the CBEGs.
      Epithelialization was noted in all patients. CONCLUSION: This engraftment
      technique has several advantages. The CBEG is much easier to handle than the
      conventional cultured epidermal autograft. It eliminates the invasive second
      procedure for skin harvesting, with resulting pain and scarring. The application
      of the CBEG can be easily performed at the bedside.

PMID- 11242308
TI  - Intracranial intubation in patients with maxillofacial injuries associated with
      base of skull fractures?

PMID- 11242309
TI  - The use of hypertonic saline in the treatment of traumatic brain injury.

PMID- 11242310
TI  - Esophageal fish bone impaction.

PMID- 11242311
TI  - Application of an artificial neural network.

PMID- 11242312
TI  - Family presence during trauma resuscitation.

PMID- 11242313
TI  - GENITAL TRAUMA DUE TO ANIMAL BITES.
AB  - PURPOSE: Animal bites to the external genitalia are rare. We retrospectively
      evaluated our experience with treating genital trauma caused by animal attacks.
      MATERIALS AND METHODS: We studied the medical records of 10 patients treated in
      the surgical emergency department at our hospital who presented with genital
      injury caused by an animal bite from 1983 to 1999. Special attention was given to
      the severity of injury, surgical treatment, antibiotic prophylaxis and outcome.
      RESULTS: Of the 2 men and 8 boys 8 were attacked by dogs, 1 by a horse and 1 by a
      donkey, respectively. In all cases initial local treatment involved debridement
      and copious wound irrigation with saline and povidone-iodine solution. Five
      patients who presented with minimal or no skin loss underwent primary skin
      closure, including 2 in whom urethral lacerations were surgically repaired. There
      was moderate to extensive tissue loss in 5 patients, including degloving penile
      injury in 2, traumatic spermatic cord amputation in 1, complete penile and
      scrotal avulsion in a 5-month-old infant, and partial penectomy in 1.
      Reconstructive procedures provided satisfactory cosmetic and functional results
      in 8 cases. Antibiotic prophylaxis was administered in all patients and no
      infectious complications developed. CONCLUSIONS: Animal bite is a rare but
      potentially severe cause of genital trauma and children are the most common
      victims. Morbidity is directly associated with the severity of the initial wound.
      Because patients tend to seek medical care promptly, infectious complications are
      unusual. Management involves irrigation, debridement, antibiotic prophylaxis, and
      tetanus and rabies immunization as appropriate as well as primary wound closure
      or surgical reconstruction. Good functional and cosmetic results are possible in
      the majority of cases.

PMID- 11242315
TI  - Preferences, quality, and the (under)utilization of total joint arthroplasty.

PMID- 11242316
TI  - Determining the need for hip and knee arthroplasty: the role of clinical severity
      and patients' preferences.
AB  - BACKGROUND: Area variation in the use of surgical interventions such as
      arthroplasty is viewed as concerning and inappropriate. OBJECTIVES: To determine
      whether area arthroplasty rates reflect patient-related demand factors, we
      estimated the need for and the willingness to undergo arthroplasty in a high- and
      a low-use area of Ontario, Canada. RESEARCH DESIGN: Population-based mail and
      telephone survey. SUBJECTS: All adults aged > or =55 years in a high (n = 21,925)
      and low (n = 26,293) arthroplasty use area. MEASURES: We determined arthritis
      severity and comorbidity with questionnaires, established the presence of
      arthritis with examination and radiographs, and evaluated willingness to have
      arthroplasty with interviews. Potential arthroplasty need was defined as severe
      arthritis, no absolute contraindication for surgery, and evidence of arthritis on
      examination and radiographs. Estimates of need were then adjusted for patients'
      willingness to undergo arthroplasty. RESULTS: Response rates were 72.0% for
      questionnaires and interviews. The potential need for arthroplasty was 36.3/1,000
      respondents in the high-rate area compared with 28.5/1,000 in the low-rate area
      (P <0.0001). Among individuals with potential need, only 14.9% in the high-rate
      area and 8.5% in the low-rate area were definitely willing to undergo
      arthroplasty (P = 0.03), yielding adjusted estimates of need of 5.4/1,000 and
      2.4/1,000 in the high- and low-rate areas, respectively. CONCLUSIONS:
      Demonstrable need and willingness were greater in the high-rate area, suggesting
      these factors explain in part the observed geographic rate variations for this
      procedure. Among those with severe arthritis, no more than 15% were definitely
      willing to undergo arthroplasty, emphasizing the importance of considering both
      patients' preferences and surgical indications when evaluating need and
      appropriateness of rates for surgery.

PMID- 11242317
TI  - "Death" and the valuation of health-related quality of life.
AB  - BACKGROUND AND OBJECTIVES: Despite evidence to the contrary, a common assumption
      in the area of health status measurement is that the state "dead" is the worst
      possible health state and by definition should be assigned a value of 0. However,
      the value of the state "dead" and the notion of states worse than "dead" have
      never been fully addressed as a research topic. This article demonstrates the
      extent of the variation in the value given to the state "dead" by individuals and
      the effects of transformation on individual and aggregate values using data
      elicited with 2 methods (visual analog scale rating and ranking) that place no
      constraint on the value given to the state "dead." RESEARCH DESIGN: Face-to-face
      interviews were conducted with 253 adults in North Yorkshire, UK, in 1998. Each
      participant performed ranking and visual analog scale rating exercises for 19
      EuroQol EQ-5D health states. CONCLUSIONS AND RESULTS: Data showed that there is a
      small group of individuals who, when given the option, choose to place relatively
      high value on the state "dead" compared with other health states. This did not
      appear to be due to artifact. Evidence also suggested that the usual assumptions
      underlying the transformation of health state values, for which the distance
      between full health and "dead" is used to define the denominator, may not hold
      for these individuals and may distort aggregate preference structures. The
      authors stress the need for more systematic inquiry in this field.

PMID- 11242318
TI  - Measuring and predicting surgeons' practice styles for breast cancer treatment in
      older women.
AB  - BACKGROUND: Few measures exist to assess physicians' practice style, and there
      are few data on physicians' practice styles and patterns of care. OBJECTIVES: To
      use clinical vignettes to measure surgeons' "propensity" for local treatments for
      early-stage breast cancer and to describe factors associated with propensity.
      RESEARCH DESIGN AND SUBJECTS: A cross-sectional mailed survey with telephone
      follow-up of a random sample of 1,000 surgeons treating Medicare beneficiaries in
      fee-for-service settings. MEASURES: Outcome measures include treatment
      propensity, self-reported practice, and actual treatment received by the
      surgeons' patients. RESULTS: Propensities were significantly associated with
      actual treatment, controlling for covariates. Area Medicare fees were the
      strongest predictor of propensity, followed by region, attitudes, volume, and
      gender. For instance, after other factors were considered, surgeons practicing in
      areas with the highest breast-conserving surgery (BCS) fees were 8.61 (95% CI
      2.26-32.73) times more likely to have a BCS propensity than surgeons in areas
      with the lowest fees. Surgeons with the strongest beliefs in patient
      participation in treatment decisions were nearly 6 times (95% CI 1.67-20.84) more
      likely to have a BCS propensity than surgeons with the lowest such beliefs,
      controlling for covariates. Male surgeons were also independently more likely to
      have a mastectomy propensity than female surgeons. CONCLUSIONS: Surgeons'
      propensities explain some of the observed variations in breast cancer treatment
      patterns among older women. Standardized scenarios provide a practical method to
      measure practice style and could be used to evaluate physician contributions to
      shared decision making, practice patterns, costs and outcomes, and adherence to
      guidelines.

PMID- 11242319
TI  - Effect of treatment on quality of life among men with clinically localized
      prostate cancer.
AB  - BACKGROUND: Quality-of-life outcomes are an important consideration for patients
      evaluating therapeutic options for localized prostate cancer. OBJECTIVES: The
      objective of this study was to describe the effect of treatment choice on change
      in health-related quality of life (HRQOL) among men with clinically localized
      prostate cancer. RESEARCH DESIGN: This was a prospective observational study.
      SUBJECTS: The study subjects were 122 men with clinically localized
      adenocarcinoma of the prostate. Forty-two subjects (34%) underwent radical
      prostatectomy, 51 (42%) underwent radiation therapy, and 29 (24%) were followed
      with expectant management. MEASURES: The University of California at Los Angeles
      Prostate Cancer Quality of Life Inde- and the Medical Outcomes Study Short Form
      36 were administered before and 3 and 12 months after initial treatment. The
      study used an analysis of covariance model adjusted for baseline differences in
      clinical and demographic factors. RESULTS: Men who underwent radical
      prostatectomy experienced significant declines in urinary and sexual function and
      bother that persisted at 12 months after treatment. Men treated with radiation
      therapy experienced smaller but significant declines in sexual function and a
      decline in social function. Expectant management patients did not have a
      significant change in disease-targeted or generic HRQOL domains. Differential
      rates of change in urinary and sexual function between treatment groups persisted
      after adjustment for differences in pretreatment clinical and demographic
      factors. CONCLUSIONS: Men undergoing radical prostatectomy have substantial
      declines in urinary and sexual function, and men undergoing radiotherapy have
      declines in sexual function. Men undergoing expectant management have no change
      in disease-specific or general HRQOL in the first year after treatment.

PMID- 11242320
TI  - Physicians' assessments of their ability to provide high-quality care in a
      changing health care system.
AB  - BACKGROUND: With the growth of managed care, there are increasing concerns but
      inconclusive evidence regarding deterioration in the quality of medical care.
      OBJECTIVES: To assess physicians' perceptions of their ability to provide high
      quality care and explore what factors, including managed care, affect these
      perceptions. RESEARCH DESIGN: Bivariate and multivariate analyses of the
      Community Tracking Study Physician Survey, a cross-sectional, nationally
      representative telephone survey of 12,385 patient-care physicians conducted in
      1996/1997. The response rate was 65%. PARTICIPANTS: Physicians who provide direct
      patient care for > or =20 h/wk, excluding federal employees and those in selected
      specialties. MEASURES: Level of agreement with 4 statements: 1 regarding overall
      ability to provide high-quality care and 3 regarding aspects of care delivery
      associated with quality. RESULTS: Between 21% and 31% of physicians disagreed
      with the quality statements. Specialists were generally 50% more likely than
      primary care physicians to express concerns about their ability to provide
      quality care. Generally, the number of managed care contracts, but not the
      percent of practice revenue from managed care, was negatively associated with
      perceived quality. Market-level managed care penetration independently affected
      physicians' perceptions. Practice setting affected perceptions of quality, with
      physicians in group settings less likely to express concerns than physicians in
      solo and 2-physician practices. Specific financial incentives and care management
      tools had limited positive or negative associations with perceived quality.
      CONCLUSIONS: Managed care involvement is only modestly associated with reduced
      perceptions of quality among physicians, with some specific tools enhancing
      perceived quality. Physicians may be able to moderate some negative effects of
      managed care by altering their practice arrangements.

PMID- 11242321
TI  - Improving the assessment of (in)patients' satisfaction with hospital care.
AB  - BACKGROUND: A self-report questionnaire is the most widely used method to assess
      (in)patients' satisfaction with (hospital) care. However, problems like
      nonresponse, missing values, and skewed score distributions may threaten the
      representativeness, validity, and reliability of results. We investigated which
      of alternative item-response formats maximizes desired outcomes. DESIGN: Five
      formats were compared on the basis of sample characteristics, psychometric
      properties at the scale and item levels, and patients' opinions of the
      questionnaire. SUBJECTS: Consecutively discharged patients (n=784) were sampled,
      of which a representative (sex, age, length of hospital stay) subsample of 514
      (65%) responded. MEASURES: A 54-item satisfaction questionnaire addressing 12
      aspects of care was used. Patients responded using either a 10-step evaluation
      scale ranging from "very poor" to "excellent" (E10), a 5-step evaluation scale
      ranging from "poor" to "excellent" (E5), or a 5-step satisfaction scale ranging
      from "dissatisfied" to "very satisfied" (S5). The 5-step scales were administered
      with response options presented as either boxed scale steps to be marked or words
      to be circled. RESULTS: E5 scales yielded lower means than S5 scales. However, at
      the item level, the S5 scale showed better construct validity, more variability,
      and less peaked score distributions. Circling words yielded fewer missing item
      scores than marking boxes. The E5 scale showed more desirable score distributions
      than the E10 scale, but construct validity and reliability were lower.
      CONCLUSIONS: No large differences among formats were found. However, if
      individual items are important carriers of information, a (5-step) satisfaction
      response scale, with response options presented in words next to each item,
      appears to be the optimal format.

PMID- 11242322
TI  - Linkage to medical services in the Drug Abuse Treatment Outcome Study.
AB  - BACKGROUND: An episode of substance abuse treatment is an opportunity to link
      substance-abusing patients to medical care at a time when management of medical
      problems might stabilize recovery and long-term health. However, little is known
      about the ability of organizational linkage mechanisms to facilitate the delivery
      of medical care to this population. OBJECTIVES: The goal of this study was to
      examine whether organizational linkage mechanisms facilitate medical service
      utilization in drug abuse treatment programs. RESEARCH DESIGN: This was a
      prospective secondary analysis of the Drug Abuse Treatment Outcome Study, a
      national longitudinal study of drug abuse treatment programs and their patients
      from 1991 to 1993. Hierarchical linear models evaluated the effect of on-site
      delivery, formal and informal referral, case management emphasis, and
      transportation on the log-transformed number of medical visits at the 1-month in
      treatment patient interview. MEASURES: Program directors' surveys provided
      organizational information, including the linkage mechanism used to deliver
      medical care. Patients reported the number of medical visits during the first
      month of drug abuse treatment. RESULTS: Exclusive on-site delivery increased
      medical utilization during the first month of drug abuse treatment (beta
      estimate, 0.22; standard error [SE], 0.06; P <0.001). Transportation services
      also increased 1-month medical utilization (beta estimate, 0.13; SE, 0.03; P
      <0.001). CONCLUSIONS: Exclusive on-site delivery of medical services increased
      drug abuse treatment patients' utilization of medical services in the first month
      of treatment. Transportation assistance warrants strong policy consideration as a
      facilitator of medical service delivery. Future research should clarify whether
      program-level linkage to medical services improves the patient-level outcomes of
      drug abuse treatment.

PMID- 11242323
TI  - Medicare beneficiaries' management of capped prescription benefits.
AB  - BACKGROUND: Having annual dollar limits in prescription coverage is a type of
      benefit design unique to Medicare beneficiaries. This type of coverage is found
      predominantly within private Medigap policies and Medicare+Choice plans offering
      prescription coverage. OBJECTIVES: The purpose of this study was to determine the
      impact of capped prescription benefits on efforts to reduce out-of-pocket
      prescription expenses by beneficiaries at risk for reaching their cap. RESEARCH
      DESIGN: This design was quasi-experimental, with data obtained from self
      administered questionnaires mailed to 600 Medicare HMO risk enrollees with capped
      prescription benefits. RESULTS: Data were collected on 378 Medicare enrollees for
      a 63% response rate. Approximately half of all respondents participated in > or
      =1 strategy to reduce their out-of-pocket prescription expenses. Participation in
      selected strategies included obtaining samples from physicians (39.2%), taking
      less than prescribed amounts (23.6%), and discontinuing prescribed medications
      (16.3%). Additionally, 15% of respondents indicated going without necessities,
      and 12% indicated borrowing money to pay for their prescriptions. Those who
      reached their prescription cap were more likely to participant in any one
      behavior (odds ratio [OR], 2.18), more likely to take less medication than
      prescribed (OR, 2.83), more likely to discontinue a medication (OR, 3.36), and
      more likely to obtain samples from their physician (OR, 2.02) compared with those
      who had not reached their prescription cap. CONCLUSIONS: Beneficiaries at risk
      for reaching their prescription cap are taking steps to reduce their out-of
      pocket prescription costs. Although some behaviors would be considered prudent,
      other behaviors may be placing beneficiaries at risk for drug-related morbidity
      and mortality.

PMID- 11242324
TI  - From clinical trials to real-world practice: use of atypical antipsychotic
      medication nationally in the Department of Veterans Affairs.
AB  - BACKGROUND: Although clinical trials evaluate pharmacotherapeutic interventions
      under highly controlled conditions, there remains a need to evaluate medication
      use in actual practice. METHODS: Patients prescribed atypical antipsychotic
      medications in the VA system during a 4-month period in 1999 (n = 73,981) were
      classified into 32 groups on the basis of clinical diagnosis and recent level of
      inpatient use. Variation was examined across groups in drug costs, agents,
      dosages, and duration of use. The potential impact of these medications on VA
      costs was estimated by calculating medication costs and subtracting estimated
      inpatient savings. RESULTS: A majority of patients were diagnosed with
      schizophrenia (57.2%), but substantial off-label use of these medications to
      treat other psychiatric illnesses was also evident (42.8%). Compared with
      published trials reporting average annual costs from $3,000 to $7,000, average
      annualized pharmacy costs were only $1,395 per patient because of a 58.5% VA
      price discount; relatively low dosing, especially for people with diagnoses other
      than schizophrenia; and medication prescription coverage for only 75% of the days
      in the study period. The sample averaged only 6.96 inpatient days; as a result,
      potential inpatient savings were limited. Assuming 0% to 18% inpatient savings,
      annual net drug costs are estimated to range from $500 to $1,152 per patient.
      CONCLUSIONS: Medication costs in actual practice can be substantially lower than
      in clinical trials. Atypical antipsychotic medications in actual VA practice
      incur net costs estimated at $500 to $1,152 per patient per year with substantial
      variation across clinical subgroups.

PMID- 11242326
TI  - UPCOMING SOUNDINGS ARTICLES.

PMID- 11242325
TI  - ACSM Abstracts: A Need For More Data.

PMID- 11242327
TI  - JUDICIOUS USE OF ANTIBIOTICS IN PEDIATRIC RESPIRATORY INFECTIONS 2000.

PMID- 11242328
TI  - Intraoperative Injection of Botulinum Toxin A into Orbicularis Oculi Muscle for
      the Treatment of Crow's Feet.
AB  - The purpose of this investigation was to evaluate the degree of efficacy of
      eliminating crow's feet by means of direct injection of botulinum toxin A into
      orbicularis oculi muscles under direct surgical vision during either
      blepharoplasty or face lift operations. Eighteen patients were injected with
      Botox A-14 in each orbicularis oculi muscle. Dilution was obtained by adding 4 ml
      of preservative-free saline to 100 IU of Botox A. Doses ranged from 15 to 50 IU
      in each muscle, varying according to the severity of wrinkles and intensity of
      muscle contraction. In 10 patients (56 percent), the Botox was injected
      throughout the outer surface of both orbicularis oculi dissected during a face
      lift operation. In eight other patients (44 percent), the toxin was injected into
      the inner surface of both orbicularis oculi exposed during classic blepharoplasty
      procedures. Most authors have demonstrated that the effect produced by
      transcutaneous Botox lasts between 4 and 6 months; the paralysis obtained by
      direct muscular injection was effective for 9 months in 14 patients (78 percent)
      and 10 months in the other 4 patients (22 percent). Results were documented by
      means of preinjection and postinjection photographs, videotapes, and
      electromyographs. Neither local nor general adverse effects were noted. The
      improvement obtained in crow's feet was satisfactory to the patient and to us.
      The use of Botox intraoperatively permitted at the same time not only the
      treatment of crow's feet by paralysis of orbicularis oculi muscles but also the
      correction of senile changes in the lids and face by means of either
      blepharoplasty or face-lift operations.

PMID- 11242329
TI  - Microsurgical Strategies in 74 Patients for Restoration of Dynamic Depressor
      Muscle Mechanism: A Neglected Target in Facial Reanimation.

PMID- 11242330
TI  - Treatment of Facial Wounds with Botulinum Toxin A Improves Cosmetic Outcome in
      Primates.

PMID- 11242331
TI  - Silicone Gel-Filled Breast Implant Integrity: A Retrospective Review of 478
      Consecutively Explanted Implants.

PMID- 11242332
TI  - Skeletal Muscle Reinnervation by Reduced Axonal Numbers Results in Whole Muscle
      Force Deficits.

PMID- 11242333
TI  - Sutural Expansion Osteogenesis for Management of the Bony-Tissue Defect in Cleft
      Palate Repair: Experimental Studies in Dogs.

PMID- 11242334
TI  - Microsurgical Replantation of the Amputated Nose.

PMID- 11242336
TI  - Comparative Lipoplasty Analysis of in Vivo-Treated Adipose Tissue.

PMID- 11242335
TI  - Saline-Filled Breast Implant Safety and Efficacy: A Multicenter Retrospective
      Review.

PMID- 11242337
TI  - Ultrasound-Assisted Lipectomy Using the Solid Probe: A Retrospective Review of
      100 Consecutive Cases.

PMID- 11242338
TI  - Ultrasound-Assisted Lipectomy Using the Solid Probe: A Retrospective Review of
      100 Consecutive Cases.

PMID- 11242339
TI  - Lengthening of the Postoperative Short Nose: Combined Use of a Gull-Wing Concha
      Composite Graft and a Rib Costochondral Dorsal Onlay Graft.

PMID- 11242340
TI  - Breast Augmentation: Choosing the Optimal Incision, Implant, and Pocket Plane.

PMID- 11242341
TI  - Intraoperative Injection of Botulinum Toxin A into Orbicularis Oculi Muscle for
      the Treatment of Crow's Feet.

PMID- 11242342
TI  - The Turkish Delight: A Pliable Graft for Rhinoplasty.

PMID- 11242343
TI  - Large-Volume Liposuction Complicated by Retroperitoneal Hemorrhage: Management
      Principles and Implications for the Quality Improvement Process by Mia Talmor,
      M.D., Thomas J. Fahey, II, M.D., Jeffrey Wise, B.A., Lloyd A. Hoffman, M.D., and
      Philip S. Barie, M.D., F.C.C.M.

PMID- 11242344
TI  - Aesthetic Perspectives Regarding Physically and Mentally Challenged Patients.

PMID- 11242345
TI  - Acute Burns.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Describe the pathophysiology of burn injury. 2. Calculate burn size and
      resuscitation requirements and predict survival. 3. Treat inhalation injury. 4.
      Describe preoperative selection, intraoperative procedures, and postoperative
      protocols for patients who require surgical care for their burn injuries. 5. Know
      the survival and functional outcomes of burn injury. Burn injuries are complex
      cutaneous traumas cared for by many plastic surgeons. Care is stratified by burn
      size, depth, and associated injuries. Advances in surgical technique, wound care,
      and bioengineered skin have resulted in excellent outcomes for most burn
      survivors. Moderate burn injuries can be treated effectively by an interested and
      experienced plastic surgeon. (Plast. Reconstr. Surg. 105: 2482, 2000.)

PMID- 11242346
TI  - A Classification System and Algorithm for Reconstruction of Maxillectomy and
      Midfacial Defects.

PMID- 11242347
TI  - Free Anterolateral Thigh Flap for Reconstruction of Head and Neck Defects
      following Cancer Ablation.

PMID- 11242348
TI  - Neonatal Induction of Tolerance to Skeletal Tissue Allografts without
      Immunosuppression.

PMID- 11242350
TI  - Nonsurgical Breast Enlargement Using an External Soft-Tissue Expansion System.

PMID- 11242349
TI  - Acute Burns.

PMID- 11242351
TI  - Human-Derived and New Synthetic Injectable Materials for Soft-Tissue
      Augmentation: Current Status and Role in Cosmetic Surgery.

PMID- 11242353
TI  - A Prospective Analysis of Patients Undergoing Silicone Breast Implant
      Explantation.

PMID- 11242352
TI  - A Prospective Analysis of Patients Undergoing Silicone Breast Implant
      Explantation.

PMID- 11242354
TI  - Reduction of Lower Palpebral Bulge by Plicating Attenuated Orbital Septa: A
      Technical Modification in Cosmetic Blepharoplasty.

PMID- 11242356
TI  - In Search of the Ideal Nose.

PMID- 11242355
TI  - In Search of the Ideal Nose.

PMID- 11242357
TI  - Sonography of Nasal Tip Anatomy and Surgical Tip Refinement.

PMID- 11242358
TI  - Progressive Tension Sutures: A Technique to Reduce Local Complications in
      Abdominoplasty.

PMID- 11242359
TI  - Traumatic Abdominal Wall Pseudolipoma following Suction-Assisted Lipectomy.

PMID- 11242360
TI  - Relevance of the Lesser Occipital Nerve in Facial Rejuvenation Surgery.

PMID- 11242362
TI  - Schematic Representations.

PMID- 11242361
TI  - Suction Mammaplasty: The Use of Suction Lipectomy to Reduce Large Breasts.

PMID- 11242363
TI  - Complications of Postmastectomy Breast Reconstruction in Smokers, Ex-smokers, and
      Nonsmokers.

PMID- 11242364
TI  - Tissue Engineering of Peripheral Nerves: A Comparison of Venous and Acellular
      Muscle Grafts with Cultured Schwann Cells.

PMID- 11242365
TI  - AlloDerm for Dorsal Nasal Irregularities.

PMID- 11242366
TI  - The Use of AlloDerm for the Correction of Nasal Contour Deformities.

PMID- 11242367
TI  - The "Nordstrom Suture" to Enhance Scalp Reductions.

PMID- 11242368
TI  - Combined Erbium:YAG Laser Resurfacing and Face Lifting.

PMID- 11242370
TI  - Corrugator Supercilii Resection through Blepharoplasty Incision.

PMID- 11242369
TI  - A Lesson from the High Tech Economic Boom: Use the Competitive Advantage of
      Plastic Surgery.

PMID- 11242371
TI  - Nomenclature and classification of lumbar disc pathology.

PMID- 11242372
TI  - Effects of chondroitinase ABC on intradiscal pressure in sheep: an in vivo study.
AB  - STUDY DESIGN: In vivo intradiscal measurements of pressure in lumbar discs
      treated with chondroitinase ABC were performed. OBJECTIVE: To determine the
      decrease in lumbar intradiscal pressure after chemonucleolysis by chondroitinase
      ABC in sheep. SUMMARY OF BACKGROUND DATA: No previous study has assessed in vivo
      intradiscal pressure after chemonucleolysis. This study investigated the effect
      of chondroitinase ABC on intradiscal pressure in terms of a dose and time
      relation. It also included roentgenographic observations and evaluation of the
      correlation between disc space narrowing and decrease in intradiscal pressure.
      METHODS: Chondroitinase ABC was injected in the lumbar intervertebral discs of
      sheep at doses of 1, 5, and 50 U. Phosphate buffered saline also was injected as
      a negative control measure. One week before injection, then 1 and 4 weeks
      afterward, intradiscal pressure was measured using a catheter microtip pressure
      transducer. Simultaneously, standard lateral roentgenographs were taken, and the
      disc height index was calculated. RESULTS: The intradiscal pressure clearly was
      decreased 1 week after chondroitinase ABC injection. A further decrease was
      observed up to 4 weeks. This pressure decrease was dose dependent. The disc
      height indexes also decreased with time, but the state of the change was
      different from that of the changes in intradiscal pressure. No clear quantitative
      correlation was found between intradiscal pressure and disc height index.
      CONCLUSIONS: Chondroitinase ABC can induce the reduction of intradiscal pressure
      in the lumbar spine.

PMID- 11242373
TI  - Improved lumbar vertebral interbody fusion using rhOP-1: a comparison of
      autogenous bone graft, bovine hydroxylapatite (Bio-Oss), and BMP-7 (rhOP-1) in
      sheep.
AB  - STUDY DESIGN: After disc removal and monosegmental instrumentation of the sheep
      lumbar spine, interbody fusion was compared for 6 months after administration of
      autogenous bone graft, hydroxylapatite, or rhOP-1. OBJECTIVE: To determine
      whether the use of rhOP-1 or hydroxylapatite would improve on the intercorporal
      fusion achieved by autologous bone grafting. SUMMARY OF BACKGROUND DATA: Spinal
      fusion often fails or shows loss of correction despite large-scale conventional
      techniques using posterior and anterior access. Also, additional operations to
      obtain bone grafts are required, which increase morbidity and strain for the
      patient, but do not always provide bone with sufficient primary stability and
      high osteogenic potential. METHODS: Vertebral fusion quality was examined by
      plain radiograph at 4-week intervals, by scintigraphy at 3 and 6 months, and by
      computed tomography scan, magnetic resonance imaging, biomechanical testing, and
      histologic evaluation. RESULTS: All examination methods demonstrated superior
      fusion after administration of rhOP-1, with radiologic fusion apparent at 4
      months. Autologous bone grafts eventually produced bony healing in most cases,
      albeit of a lower quality than with rhOP-1. Hydroxylapatite use led only to the
      formation of a tight pseudarthrosis. CONCLUSIONS: The results indicate that rhOP
      1 use is an appropriate method for improving interbody fusion in the sheep spine.
      In addition to offering the potential for improved bone healing, rhOP-1 use may
      permit less invasive surgery such as transpedicular fusion and the use of cages.

PMID- 11242374
TI  - Long-term results of double-door laminoplasty for cervical stenotic myelopathy.
AB  - STUDY DESIGN: A retrospective study of the long-term results from double-door
      laminoplasty (Kurokawa's method) for patients with myelopathy caused by
      ossification of the posterior longitudinal ligament and cervical spondylosis was
      performed. OBJECTIVE: To know whether the short-term results from double-door
      laminoplasty were maintained over a 10-year period and, if not, the cause of late
      deterioration. SUMMARY OF BACKGROUND DATA: There are few long-term follow-up
      studies on the outcome of laminoplasty for cervical stenotic myelopathy. METHODS:
      In this study, 35 patients with cervical myelopathy caused by ossification of the
      posterior longitudinal ligament in the cervical spine and 25 patients with
      cervical spondylotic myelopathy, including 5 patients with athetoid cerebral
      palsy, underwent double-door laminoplasty from 1980 through 1988 and were
      followed over the next 10 years. The average follow-up period was 153 months
      (range, 120-200 months) in patients with ossification of the posterior
      longitudinal ligament and 156 months (range, 121-218 months) in patients with
      cervical spondylotic myelopathy. Neurologic deficits before and after surgery
      were assessed using a scoring system proposed by the Japanese Orthopedic
      Association (JOA score). Patients who showed late deterioration received further
      examination including computed tomography scan and magnetic resonance imaging of
      the cervical spine. RESULTS: In 32 of the patients with ossification of the
      posterior longitudinal ligament and 23 of the patients with cervical spondylotic
      myelopathy, myelopathy improved after surgery. The improvement of Japanese
      Orthopedic Association scores was maintained up to the final follow-up assessment
      in 26 of the patients with ossification of the posterior longitudinal ligament
      and 21 of the patients with cervical spondylotic myelopathy. Late neurologic
      deterioration occurred in 10 of the patients with ossification of the posterior
      longitudinal ligament an average of 8 years after surgery, and in 4 of the
      patients with cervical spondylotic myelopathy, including the 3 patients with
      athetoid cerebral palsy, an average of 11 years after surgery. The main causes of
      deterioration in patients with ossification of the posterior longitudinal
      ligament were a minor trauma in patients with residual cervical cord compression
      caused by ossification of the posterior longitudinal ligament and thoracic
      myelopathy resulting from ossification of the yellow ligament in the thoracic
      spine. CONCLUSIONS: The short-term results of laminoplasty for cervical stenotic
      myelopathy were maintained over 10years in 78% of the patients with ossification
      of the posterior longitudinal ligament, and in most of the patients with cervical
      spondylotic myelopathy, except those with athetoid cerebral palsy. Double-door
      laminoplasty is a reliable procedure for individuals with cervical stenotic
      myelopathy.

PMID- 11242375
TI  - Long-term follow-up results of anterior interbody fusion applied for cervical
      myelopathy due to ossification of the posterior longitudinal ligament.
AB  - STUDY DESIGN: A long-term follow-up study was carried out in 30 patients who
      underwent anterior interbody fusion for cervical myelopathy associated with
      ossification of the posterior longitudinal ligament (OPLL). OBJECTIVE: To
      investigate whether anterior interbody fusion without decompression is an
      appropriate surgical method for long-term relief of cervical OPLL myelopathy.
      SUMMARY OF BACKGROUND DATA: Several studies of operative results after posterior
      decompression for cervical myelopathy due to ossification of the posterior
      longitudinal ligament have been reported. There has been no report about anterior
      interbody fusion without decompression. The postoperative results of this
      treatment method applied in cervical OPLL myelopathy have been evaluated by the
      authors of the present study for more than 10 years. No reports on such a long
      term follow-up study have been published in the literature. METHODS: Thirty
      patients who underwent anterior interbody fusion for cervical OPLL myelopathy
      were evaluated clinically and radiographically. The mean follow-up period was
      14.7 years (range, 10-23 years). RESULTS: Clinical results were evaluated
      according to Okamoto's classification. At the time of the final follow-up
      evaluation, 16 patients had improved in functional score by two grades, and their
      surgical results were regarded as excellent; eight patients improved by one
      grade, and their clinical outcomes were regarded as good; five patients showed no
      change; and the condition of one patient deteriorated. As for radiographic
      analysis, the type of ossification had changed in four cases. Ossification width
      and thickness increased in 26 patients. Postoperative alignment of the cervical
      spine showed kyphosis in three patients, straight spine in 11 patients, and
      lordosis in 16 patients. CONCLUSION: Anterior interbody fusion without
      decompression is an effective treatment for cervical OPLL myelopathy that
      resulted in stable long-lasting conditions.

PMID- 11242376
TI  - Quality of life in elderly patients with ossification of the posterior
      longitudinal ligament.
AB  - STUDY DESIGN: A longitudinal cohort study of 216 elderly patients with
      ossification of the posterior longitudinal ligament for an average of 13 years
      was performed. OBJECTIVE: To know the quality of life experienced by patients
      after treatment. SUMMARY OF BACKGROUND DATA: No report is available on the
      quality of life experienced by elderly patients with ossification of the
      posterior longitudinal ligament. Because the life prognosis of patients with this
      condition is relatively good, the quality of life experienced by elderly patients
      with this disease is an important subject. METHODS: The study participants were
      216 elderly patients with ossification of the posterior longitudinal ligament.
      Conservative therapy was performed for 126 patients, and surgical therapy for 90
      patients. Surgery was basically indicated for patients with myelopathy, who were
      classified using Nurick's grading system. The cumulative survival rate of these
      patients and their disabilities in daily living were reviewed. The occurrence of
      fracture resulting from osteoporosis was surveyed, and the relation of such
      fractures to bone mineral density was examined. RESULTS: The cumulative survival
      rate of 70-year-old patients exhibiting Nurick Grade 5 severe myelopathy before
      treatment was 20%, whereas that of patients without myelopathy or those with
      Grades 1, 2, 3, or 4 myelopathy before treatment was 80%. Patients who underwent
      surgical therapy for Grade 3 or 4 myelopathy were statistically more likely to be
      independent of assistance with activities of daily living than those with similar
      degrees of myelopathy who underwent conservative therapy. The final quality of
      life was poor for patients with Grade 5 myelopathy at the first examination,
      regardless of therapeutic method. The prevalence of complication by fracture in
      patients with ossification of the posterior longitudinal ligament was 1.4% for
      men and 8.6% for women. The bone mineral density in these patients without
      myelopathy was significantly higher than in healthy subjects of the same age.
      CONCLUSION: The study data suggest that surgical treatment should be chosen for
      patients exhibiting moderate myelopathy to obtain satisfactory quality of life
      for them over a long period.

PMID- 11242377
TI  - Spondylodiscitis and infective endocarditis: case studies and review of the
      literature.
AB  - STUDY DESIGN: This study evaluated the association between infective endocarditis
      and infective spondylodiscitis and its clinical features. OBJECTIVES: To report
      case studies of patients with spondylodiscitis complicating infective
      endocarditis. SUMMARY OF BACKGROUND DATA: Early diagnosis of infective
      endocarditis as the source of the spondylodiscitis is often difficult because
      clinical and radiologic patterns are similar to those present in spondylodiscitis
      alone. METHODS: The case records of the patients with infective endocarditis
      admitted to our Department from 1991-1998 were reviewed. The diagnosis of
      spondylodiscitis was made on the basis of clinical features and of typical
      radiologic signs. RESULTS: Among 30 patients affected by infective endocarditis,
      three also were affected by spondylodiscitis. All patients fully recovered after
      appropriate antibiotic therapy. CONCLUSIONS: In all patients with
      spondylodiscitis, infective endocarditis should be excluded, particularly in
      patients with a history of heart valve disease.

PMID- 11242379
TI  - Radiologic findings and curve progression 22 years after treatment for adolescent
      idiopathic scoliosis: comparison of brace and surgical treatment with matching
      control group of straight individuals.
AB  - STUDY DESIGN: This study is a follow-up investigation for a consecutive series of
      patients with adolescent idiopathic scoliosis treated between 1968 and 1977. In
      this series, 156 patients underwent surgery with distraction and fusion using
      Harrington rods, and 127 were treated with brace. OBJECTIVES: To determine the
      long-term outcome in terms of radiologic findings and curve progression at least
      20 years after completion of the treatment. SUMMARY OF BACKGROUND DATA:
      Radiologic appearance is important in comparing the outcome of different
      treatment options and in evaluating clinical results. Earlier studies have shown
      a slight increase of the Cobb angle in brace-treated patients with time, but not
      in fused patients. METHODS: Of 283 patients, 252 attended a clinical and
      radiologic follow-up assessment by an unbiased observer (91% of the surgically
      treated and 87% of the brace-treated patients). This evaluation included chart
      reviews, validated questionnaires, clinical examination, and full-length standing
      frontal and lateral roentgenographs. Curve size was measured by the Cobb method
      on anteroposterior roentgenograms as well as by sagittal contour and balance on
      lateral films. The occurrence of any degenerative changes or other complications
      was noted. An age- and gender-matched control group of 100 individuals was
      randomly selected and subjected to the same examinations. RESULTS: The mean
      follow-up times were 23 years for surgically treated group and 22 years for brace
      treated group. The deterioration of the curves was 3.5 degrees for all the
      surgically treated curves and 7.9 degrees for all the brace-treated curves (P <
      0.001). Five patients, all brace-treated, had a curve increase of 20 degrees or
      more. The overall complication rate after surgery was low: Pseudarthrosis
      occurred in three patients, and flat back syndrome developed in four patients.
      Eight of the patients treated with fusion (5.1%) had undergone some additional
      curve-related surgical procedure. The lumbar lordosis was less in the surgically
      treated than in the brace-treated patients or the control group (mean, 33 degrees
      vs 45 degrees and 44 degrees, respectively). Both surgically treated and brace
      treated patients had more degenerative disc changes than the control participants
      (P < 0.001), but no significant differences were found between the scoliosis
      groups. No statistically significant difference in terms of radiographically
      detectable degenerative changes in the unfused lumbar discs was found between
      patients fused below L3 or those fused to L3 and above (P = 0.22). A study on
      intra- and interobserver measurements of kyphosis, lordosis, and sagittal
      vertical axis on two films for each patient demonstrated that the repeatability
      of measuring sagittal plumbline on two different lateral radiographs, with
      patients moving between radiograms, was unreliable for comparison. CONCLUSIONS:
      Although more than 20 years had passed since completion of the treatment, most of
      the curves did not increase. The surgical complication rate was low. Degenerative
      disc changes were more common in both patient groups than in the control group.

PMID- 11242378
TI  - Injection therapy for subacute and chronic benign low back pain.
AB  - STUDY DESIGN: The Medline and Embase databases containing randomized controlled
      trials of injection therapy published to 1998 were systematically reviewed.
      OBJECTIVES: To evaluate the effectiveness of injection therapy with anesthetics,
      steroids, or both in patients with low back pain persisting longer than 1 month.
      METHODS: Two reviewers independently assessed the trials for the quality of their
      methods. The primary outcome measure was pain relief. Subgroup analyses were
      performed between trials with different control groups (placebo and active
      injections), with different injection sites (facet-joint, epidural, and local
      injections), and with timing of outcome measurement (short- and long-term).
      Within the resulting 12 (2 x 3 x 2) subcategories of studies, the overall
      relative risks and corresponding 95% confidence intervals were estimated, using
      the random effects model of DerSimonian and Laird. In the case of trials using
      active injections as a control, the results were not pooled. RESULTS: This review
      included 21 randomized trials. All the studies involved patients with low back
      pain persisting longer than 1 month. Only 11 studies compared injection therapy
      with placebo injections (explanatory trials). The methodologic quality of many
      studies was low: Only eight studies had a methodologic score of 50 points or
      more. There were only three well-designed explanatory clinical trials: one on
      injections into the facet joints with a short-term relative risk of 0.89 (95%
      confidence interval = 0.65-1.21) and a long-term relative risk of 0.90 (95%
      confidence interval = 0.69-1.17), one on epidural injections with a short-term
      relative risk of of 0.94 (95% confidence interval = 0.76-1.15) and a long-term
      relative risk of 1.00 (95% confidence interval = 0.71-1.41), and one on local
      injections with a long-term relative risk of 0.79 (95% confidence interval = 0.65
      0.96). Within the six subcategories of explanatory studies, the pooled relative
      risks were as follows: facet joint, short-term: relative risk = 0.89 (95%
      confidence interval = 0.65-1.21); facet joint, long-term: relative risk = 0.90
      (95% confidence interval = 0.69-1.17); epidural, short-term: relative risk = 0.93
      (95% confidence interval = 0.79-1.09); epidural, long-term: relative risk = 0.92
      (95% confidence interval = 0.76-1.11); local, short-term: relative risk = 0.80
      (95% confidence interval = 0.40-1.59); and local, long-term: relative risk = 0.79
      (95% confidence interval = 0.65-0.96). CONCLUSIONS: Convincing evidence is
      lacking regarding the effects of injection therapy on low back pain. Additional
      well-designed explanatory trials in this field are needed.

PMID- 11242380
TI  - Multiple vertebral osteotomies in the treatment of rigid adult spine deformities.
AB  - STUDY DESIGN: Retrospective review of the clinical and radiographic results in
      adult revision spine deformity surgery using the techniques of osteotomies to
      effect spine balance and curve correction. OBJECTIVES: To assess the efficacy of
      multiple vertebral osteotomies in correction of rigid spine deformities in adult
      patients undergoing revision surgery. METHOD: The records and radiographs of 27
      adult patients with idiopathic scoliosis who underwent revision surgery requiring
      anterior release (discectomy and/or osteotomy) and posterior osteotomy to correct
      rigid spinal deformities were retrospectively reviewed. RESULTS: All 27 patients
      were available for follow-up evaluation. Fifteen patients had anterior
      discectomies followed by posterior osteotomies, whereas 12 had anterior and
      posterior osteotomies in staged or sequential (same day) fashion. Diagnosis was
      idiopathic scoliosis for the index operation. At revision, the primary deformity
      was flatback deformity in 10 patients and pseudarthrosis with progressive
      deformity in 17 patients. Eleven patients had predominant sagittal
      decompensation, 11 patients had multiplanar decompensation, and five patients
      were balanced. The average number of osteotomies performed anteriorly was 4.3
      levels (range, 1-8) and the average number of osteotomies posteriorly was 4.6
      levels (range, 1-10). There were a total of nine complications in eight patients
      including three pseudarthroses (11%), five hardware failures (19%), and one
      transient neurologic deficit (4%). There were no deep wound infections, deep vein
      thromboses, pulmonary emboli, or deaths. The average scoliosis correction was 40%
      (range, 5-81%), whereas the average sagittal balance was corrected 6.5 cm (range,
      -5-29.5 cm), on average, and coronal balance was corrected 2.5 cm (range, 1-6
      cm), on average. CONCLUSION: This study demonstrates multiple vertebral
      osteotomies (anterior and/or posterior) in the management of rigid adult spine
      deformities and deformity correction with an acceptable complication rate. Use of
      vertebral osteotomies for patients undergoing revision spine surgery is a safe
      and reasonable approach to obtain an arthrodesis.

PMID- 11242382
TI  - Interobserver and intraobserver agreement of radiograph interpretation with and
      without pedicle screw implants: the need for a detailed classification system in
      posterolateral spinal fusion.
AB  - STUDY DESIGN: A prospective randomized clinical study in which four observers
      evaluated radiographs of posterolateral fusion masses. OBJECTIVES: To evaluate
      the accuracy of radiograph interpretation of the posterolateral spinal fusion
      mass when using a detailed classification system and to analyze the influence of
      metallic internal fixation devices on radiologic inaccuracy. SUMMARY OF
      BACKGROUND DATA: In general, the literature describing the classification
      criteria used for radiograph interpretation of spinal posterolateral fusion has
      serious deficiencies. There is a need for a detailed classification system.
      METHODS: Seventy patients were randomly allocated to receive no instrumentation
      (n = 36) or Cotrel-Dubousset instrumentation (n = 34) in posterolateral lumbar
      fusion. All four observers participated in a prestudy discussion and evaluated
      the radiographs (anteroposterior, lateral) taken at the 1-year follow-up
      evaluation. The observers scored the radiographs twice (30 days apart). Each
      level on each side was judged separately. A continuous intertransverse bony
      bridge involving at minimum one of the two sides indicated a fusion at that
      level. "Fusion" indicated this quality of fusion at all intended levels. If the
      fusion was doubtful on both sides of the interspace, the individual case could
      not be classified as "fused." RESULTS: The mean interobserver agreement was 86%
      (Kappa 0.53), and the mean intraobserver agreement was 93% (Kappa 0.78). No
      difference in interobserver and intraobserver agreement was found between
      patients with and without supplementary pedicle screw fixation. All mean Kappa
      values were classified as fair or good. The four observers identified a mean
      fusion rate of 81%. CONCLUSION: It is extremely difficult to interpret
      radiographic lumbar posterolateral fusion success. Such an assessment needs to be
      performed by use of a detailed radiographic classification system. The
      classification system presented here revealed good interobserver and
      intraobserver agreement, both with and without instrumentation. The
      classification showed acceptable reliability and may be one way to improve
      interstudy and intrastudy correlation of radiologic outcomes after posterolateral
      spinal fusion. Instrumentation did not influence reproducibility but may result
      in slightly underestimated fusion rates.

PMID- 11242383
TI  - Surfing for back pain patients: the nature and quality of back pain information
      on the Internet.
AB  - STUDY DESIGN: A prospective, systematic review of web sites related to back pain.
      OBJECTIVE: To assess the nature and quality of back pain-related information on
      the World Wide Web during a 2-year period. SUMMARY OF BACKGROUND DATA: The
      Internet has become a rich source of medical information. Limited knowledge is
      available, however, about the quality of online resources. Although previous
      systematic reviews on medical-related web sites found problems in varying degrees
      with the credibility of information, no such review was conducted to assess the
      back pain-related sites. METHODS: A search of web sites was conducted in November
      1996 using five search engines (AltaVista, Infoseek, Lycos, Yahoo, and Magellan)
      and two key terms ("back pain" and "back problems"). A sample of sites was
      evaluated by two independent reviewers. Each site was described by the type and
      nature of the sponsor, target audience, and content. Overall quality was assessed
      in terms of evidence-based information available. RESULTS: Seventy-four web sites
      were reviewed in 1996, and nine of them (12.2%) were identified as high-quality
      sites. Advertising was the focus of 80.8% of the sites. Eleven sites (14.9%) were
      found to be discontinued 1 year later, and 20 (27.0%) were not accessible by the
      reviewers at the 2-year follow-up evaluation. Of the remaining 54 sites, 44.4%
      were produced by for-profit companies, and most sites targeted people with back
      pain (63.0%). Only seven out of the nine high-quality sites held their ratings at
      the 2-year follow-up evaluation. CONCLUSION: Most back pain-related web sites can
      be classified as advertising. The quality varied considerably, resulting in
      difficulties for patients to find useful information in this field. The
      increasing number of people seeking medical information on the Web creates a need
      for more high quality sites. Further, systematic review of web sites should be
      encouraged to monitor the accuracy of Internet publication.

PMID- 11242384
TI  - Surgical treatment of thoracic spinal stenosis: a 2- to 9-year follow-up.
AB  - STUDY DESIGN: A retrospective investigation of the results of operative treatment
      of patients with symptomatic thoracic spinal stenosis. OBJECTIVES: To establish
      the effectiveness and define the limitations of surgical treatment for stenosis
      of the thoracic spinal canal. SUMMARY OF BACKGROUND DATA: In contrast to cervical
      and lumbar stenosis, symptomatic narrowing of the thoracic spinal canal is rarely
      encountered. Although the treatment of thoracic stenosis has been described in
      multiple case reports and in several small series with minimal follow-up
      evaluation, there are few studies of patients treated surgically for this
      condition with follow-up evaluation beyond 2 years. METHODS: Twelve patients who
      underwent operative decompression for symptomatic stenosis of the lower thoracic
      spine were followed up for an average period of 62.4 months. Surgery was
      performed on the thoracic spine alone in four cases and on the combined
      thoracolumbar spine in eight. Factors that were investigated included pain
      severity, lower extremity motor function, ambulatory status, and postoperative
      complications. RESULTS: The level of pain after surgery was decreased in eight
      patients and unchanged in four patients. Of the 10 patients with a motor deficit
      before surgery, eight had improvement of muscle function. Of the 11 patients with
      a gait disturbance before surgery, ambulatory status was improved in seven,
      unchanged in two, and worse in two. One patient lost neural function secondary to
      surgical intervention. There were five cases in which the early result
      subsequently deteriorated because of recurrent stenosis, spinal
      deformity/instability, or both. CONCLUSIONS: Thoracic stenosis can occur in
      isolation or, more commonly, in association with lumbar stenosis. Ideally,
      operative treatment should address all stenotic segments and directly decompress
      the primary anatomic abnormalities causing neural element compression. Although
      satisfactory short-term results can be expected, deterioration of the early
      outcome because of the potential for recurrent stenosis and deformity/instability
      at the thoracolumbar junction can sometimes be seen with longer follow-up
      evaluation periods.

PMID- 11242386
TI  - Comparison of posterior and transforaminal approaches to lumbar interbody fusion.
AB  - STUDY DESIGN: A study of the transforaminal lumbar interbody fusion and the
      posterior lumbar interbody fusion techniques was performed. OBJECTIVES: To
      describe the transforaminal lumbar interbody fusion technique, and to compare
      operative data, including blood loss and operative time, with data from posterior
      lumbar interbody fusion technique. SUMMARY OF BACKGROUND DATA: The evolution of
      posterior lumbar fusion combined with anterior interbody fusion has resulted in
      increased fusion rates as well as improved reductions and stability. The
      transforaminal lumbar interbody fusion technique pioneered by Harms and Jeszensky
      offers potential advantages and provides a surgical alternative to more
      traditional methods. METHODS: In 13 consecutive months, two spinal surgeons
      performed 40 transforaminal lumbar interbody fusions and 34 posterior lumbar
      interbody fusion procedures. Data regarding blood loss, operative times, and
      length of hospital stay were recorded. These data were analyzed using analysis of
      variance to show any significant differences between the two techniques. To
      determine whether differences in measured variables were dependent on patient
      gender or number of levels fused, epsilon(chi2) analysis was used. RESULTS: No
      significant differences were found between transforaminal and posterior lumbar
      interbody fusions in terms of blood loss, operative time, or duration of hospital
      stay when a single-level fusion was performed. Significantly less blood loss
      occurred when a two-level fusion was performed using the transforaminal approach
      instead of the posterior approach (P < 0.01). Differences in measured variables
      for the two procedures were independent of patient age, gender, and the number of
      levels fused. There were no complications with the transforaminal approach, but
      the posterior approach resulted in multiple complications. CONCLUSIONS: In this
      comparison of patients receiving transforaminal lumbar interbody fusion versus
      posterior lumbar interbody fusion, no complications occurred with the
      transforaminal approach, whereas multiple complications were associated with the
      posterior approach. Similar operative times, blood loss, and duration of hospital
      stay were obtained in single-level fusions, but significantly less blood loss
      occurred with the transforaminal lumbar interbody approach in two-level fusions.
      The transforaminal procedure preserves the interspinous ligaments of the lumbar
      spine and preserves the contralateral laminar surface as an additional surface
      for bone graft. It may be performed at all lumbar levels because it avoids
      significant retraction of the dura and conus medullaris.

PMID- 11242387
TI  - Paired cylindrical interbody cage fit and facetectomy in posterior lumbar
      interbody fusion in an Asian population.
AB  - STUDY DESIGN: The intervertebral disc heights and interfacetal distances of
      normal lower lumbar segments were measured from MRI scans of 150 male subjects.
      OBJECTIVES: To investigate the probabilities of paired cylindrical interbody cage
      placement across the facet joints of the lower lumbar spine in an Asian
      population with respect to the spinal segmental level, facetectomy, and the
      restoration of normal intervertebral height. SUMMARY OF BACKGROUND DATA:
      Cylindrical interbody cage devices often require extensive facetectomy for
      insertion through a posterior approach in a posterior lumbar interbody fusion
      (PLIF) procedure. This is because the transverse dimension of a pair of cages
      could far exceed the interfacetal interval of the lumbar segment. METHODS: One
      hundred and fifty MRI scans of the lumbosacral spine of male patients between the
      ages of 18 and 55 years undergoing investigation for low back pain were collected
      for this study. The interfacetal distances and intervertebral disc heights were
      measured from transverse and sagittal images, respectively, at L3/L4, L4/L5 and
      L5/S1. Degenerated discs were not measured. The inner, mid, and outer
      interfacetal distances were compared with the dimensions of paired cages of 13,
      15, and 17 mm in diameter to obtain the proportion of lumbar segments at a
      particular spinal level that would accommodate paired cages of different
      diameters and under conditions of varying degrees of facetectomy. RESULTS:
      Without facetectomy, there was no lumbar segment that could accommodate paired
      cages as well as restore intervertebral height. With hemi-facetectomy, very few
      segments at L3/L4 and L4/L5 could fit paired cages. At L5/S1, fewer than 9% of
      segments could fit paired cages and restore intervertebral heights. The
      proportion of segments that could accommodate paired cages increased with near
      total facetectomy: 25% of L5/S1 segments could accommodate 15-mm cages with
      restoration of intervertebral heights. CONCLUSIONS: Paired cylindrical cage
      installation in the majority of patients is likely to require near-total or total
      facetectomy, with implications for potential segmental instability. Among the
      three lumbar segments studied, L5/S1 had the highest proportion of segments that
      could accommodate paired cages and at the same time restore intervertebral
      height.

PMID- 11242388
TI  - Delayed effects of a migrated foreign body (sewing needle) in the cervical spine:
      a case report.
AB  - STUDY DESIGN: A case report is presented. OBJECTIVE: This report documents one
      case of intraspinal migration of a metal foreign body. SUMMARY OF BACKGROUND
      DATA: The migration and penetration of foreign bodies into the spine have been
      described, but there are only three reports of a needle as the causative object.
      METHODS: This case report included a chart review, an examination of the patient,
      and a literature search. RESULTS: The patient successfully underwent surgery, in
      which the foreign body (a sewing needle) was removed. CONCLUSION: It is important
      to be aware of the possible delayed penetration of a foreign body into the spine
      even in patients with few or no symptoms.

PMID- 11242389
TI  - Pedicle fracture after instrumented posterolateral lumbar fusion: a case report.
AB  - STUDY DESIGN: The case report of a 60-year-old man with late onset back pain
      after lumbar spine fusion is presented. OBJECTIVE: To report the rare
      complication of bilateral pedicle stress fractures after instrumented
      posterolateral lumbar fusion. SUMMARY OF BACKGROUND DATA: A 56-year-old man
      underwent revision spinal surgery for ongoing back pain secondary to
      pseudoarthroses. A posterolateral L4-S1 instrumented fusion using pedicle screws
      was performed. Autologous bone graft was applied to the decorticated lateral
      masses. The internal fixation was removed 2 years later, at which time plain
      radiographs showed that the fusion mass was solid. At the age of 60 years, the
      man presented with worsening back pain. Plain radiographs and computed
      tomographic scans demonstrated bilateral L4 pedicle stress fractures. A bone scan
      indicated that these were recent in origin. METHOD: The clinical assessment was
      undertaken by the senior author and surgeon. Investigations included plain
      radiography, computer tomography, and scintographic imaging. A systematic
      literature review of the relevant publications was performed. RESULTS: In the
      reported patient, bilateral pedicle stress fractures developed 2 years after
      pedicle screw removal from an L4-S1 instrumented posterolateral lumbar spine
      fusion. This occurred at the uppermost level of the fusion mass. CONCLUSIONS: The
      pedicle is the weakest point in the neural arch after posterolateral fusion.
      Although movement continues at the level of the disc space anteriorly, the
      pedicle is susceptible to fracture. Pedicle fracture is a rare late complication
      of posterolateral lumbar spine fusion.

PMID- 11242390
TI  - Late operative site pain with isola posterior instrumentation requiring implant
      removal: infection or metal reaction?
AB  - OBJECTIVES: To elucidate the cause of late operative site pain in six cases of
      scoliosis managed with Isola posterior instrumentation that required removal of
      the implants. METHOD: Microbiologic examination of wound swabs and enriched
      culture of operative tissue specimens was undertaken in all cases. Histologic
      study of the peri-implant membranes also was conducted. RESULTS: The presentation
      in all cases was similar: back pain appearing between 12-20 months after surgery,
      followed by a local wound swelling leading to a wound sinus. In only one of these
      cases was the discharge positive for bacterial growth. Implant removal was
      curative. Histologic examination of tissue specimens revealed a neutrophil-rich
      granulation tissue reaction suggestive of an infective etiology despite the
      failure to isolate organisms. Within the granulation tissue was metallic debris
      that varied from very sparse to abundant from fretting at the distal cross
      connector junctions. A review of recent literature describing similar problems
      suggests that late onset spinal pain is a real entity and a major cause of
      implant removal. CONCLUSIONS: On reviewing the evidence for an infective etiology
      versus a metallurgic reaction etiology for these cases of late onset spinal pain,
      it was concluded that a subacute low-grade implant infection was the main cause.
      Histologic findings would seem to confirm low-grade infection. There may be more
      than one causative factor for late operative site pain, as it is possible that
      fretting at cross connection junctions may provide the environment for the
      incubation of dormant or inactive microbes.

PMID- 11242391
TI  - Pyogenic spondylitis in an S1-S2 immobile segment.
AB  - STUDY DESIGN: A case of pyogenic spondylitis in S1-S2 is presented. OBJECTIVE: To
      describe the diagnosis and management of this rare spondylitis. SUMMARY OF
      BACKGROUND DATA: The segment including the first and second sacral vertebrae is
      not mobile. Therefore, discitis of S1-S2 and adjacent spondylitis is very rare.
      To the authors' knowledge, this is the first reported case of infectious
      spondylitis in an immobile segment: S1-S2. METHODS: In addition to radiography
      and bone scintigraphy, magnetic resonance imaging was used to confirm the
      diagnosis. Changes consistent with infectious spondylitis were shown, including
      an epidural abscess. RESULTS: The patient was treated with laparoscopic drainage
      and biopsy. Staphylococcus aureus was cultured, and adequate antibiotics were
      administered. Repeat magnetic resonance imaging at approximately 4 months
      demonstrated normal signal intensity and disappearance of the abscess.
      CONCLUSION: Findings from this study show that pyogenic spondylitis can occur in
      immobile S1-S2.

PMID- 11242392
TI  - Ossification of the posterior longitudinal ligament in vitamin D-resistant
      rickets: case report and review of the literature.
AB  - STUDY DESIGN: A case report of cervical myelopathy caused by ossification of the
      posterior longitudinal ligament in a patient with vitamin D-resistant rickets is
      presented together with a review of literature. OBJECTIVE: To report the
      diagnosis of ossification of the posterior longitudinal ligament in a white woman
      with vitamin D-resistant rickets. SUMMARY OF BACKGROUND DATA: The association
      between ossification of the posterior longitudinal ligament and untreated vitamin
      D-resistant rickets has been reported in Japan, but infrequently in white
      populations. In whites, ossification of the posterior longitudinal ligament is
      closely associated with diffuse idiopathic skeletal hyperostosis. A clear
      association between ossification of the posterior longitudinal ligament and
      vitamin D-resistant rickets in white populations has not yet been established.
      METHODS: The medical record and imaging studies of a patient treated at the
      authors' institution for cervical myelopathy caused by ossification of the
      posterior longitudinal ligament in the setting of treated vitamin D-resistant
      rickets were reviewed. A Medline search of the medical literature between 1966
      1999 was performed to identify pertinent studies and similar case reports.
      RESULTS: The occurrence of spinal stenosis in untreated adults with vitamin D
      resistant rickets has been reported in all regions of the spine in Japanese
      patients. The association between ossification of the posterior longitudinal
      ligament and untreated vitamin D-resistant rickets was first reported in Japan,
      where ossification of the posterior longitudinal ligament is endemic. This
      association may be incidental, because reports on ossification of the posterior
      longitudinal ligament in whites are not as frequent as in Japanese, reflecting
      the higher prevalence of this condition in Japan. CONCLUSION: Ossification of the
      posterior longitudinal ligament and ossification of the posterior longitudinal
      ligament associated with deranged calcium or phosphate metabolism may be
      different pathologic entities sharing a common outcome. Adequate treatment of
      vitamin D-resistant rickets may not always prevent or reverse ossification of the
      posterior longitudinal ligament.

PMID- 11242393
TI  - Re: Surgery versus conservative medical and adult isthmic spondylolisthesis
      (Spine 2000; 25: 1711-15).

PMID- 11242394
TI  - The use of nonorganic signs and symptoms as a screening tool for return to work
      in patients with acute low back pain (Spine 2000; 25:1925-31).

PMID- 11242396
TI  - Prospective comparison of flexibility radiographs in adolescent idiopathic
      scoliosis.
AB  - STUDY DESIGN: A prospective evaluation of radiographs in patients undergoing
      anterior spinal fusion or posterior spinal fusion for adolescent idiopathic
      scoliosis. OBJECTIVE: To determine the most effective preoperative radiographic
      method for evaluating coronal plane flexibility by comparing preoperative and
      postoperative correction. SUMMARY OF BACKGROUND DATA: Curve flexibility is
      traditionally evaluated with side-bending radiographs. Recently, the fulcrum
      bending radiograph was shown to provide better correction of thoracic curves
      undergoing posterior spinal fusion but was not evaluated in thoracolumbar/lumbar
      curves or in patients undergoing anterior spinal fusion. METHODS: Preoperative
      coronal radiographs of 46 consecutive patients undergoing spinal fusion for
      adolescent idiopathic scoliosis obtained while standing, lying supine, side
      bending (maximally bending while supine), push-prone (padded bolsters applied to
      chest wall while prone), and fulcrum-bending (curve apex suspended over a
      radiolucent fulcrum while lateral) were compared with standing postoperative
      radiographs. Cobb angles were determined and evaluated for statistical
      significance. RESULTS: The fulcrum-bending radiograph demonstrated statistically
      better correction than other preoperative methods for main thoracic curves (P <
      0.01) but fell short of demonstrating the correction obtained surgically. There
      was no statistical difference between side-bending, fulcrum-bending, or
      postoperative correction for thoracolumbar/lumbar curves (all P values > 0.07).
      The left side-bending was the most effective method for reducing upper thoracic
      curves (P < 0.001). There was no difference in the results obtained for curves
      corrected by anterior spinal fusion or anterior spinal fusion. CONCLUSION: To
      achieve maximal preoperative correction, thoracic fulcrum-bending radiographs
      should be obtained for evaluating main thoracic curves, whereas side-bending
      radiographs should continue to be used for evaluating both upper thoracic and
      thoracolumbar/lumbar curves.

PMID- 11242397
TI  - Cervical myelopathy and congenital stenosis from hypoplasia of the atlas: report
      of three cases and literature review.
AB  - STUDY DESIGN: Case reports of patients with cervical myelopathy to hypoplasia of
      the atlas. OBJECTIVES: To report cases of cervical myelopathy due to congenital
      hypoplasia of the atlas and to review the literature. SUMMARY OF BACKGROUND DATA:
      Six previously documented cases of congenital hypoplasia of the atlas as a cause
      of cervical myelopathy are reported in the literature. METHODS: Three patient's
      clinical record and radiologic imaging studies as well as a thorough literature
      search are reported. Plain radiographs, computed tomography scans, magnetic
      resonance images, as well as somatosensory-evoked potential changes are
      displayed. RESULTS: Cervical myelopathy developed in three patients who were
      found to have congenital hypoplasia of the atlas. Laminectomy of C1 provided
      neurologic improvement in all three patients presented. CONCLUSION: Congenital
      hypoplasia of the atlas is a rare cause of cervical myelopathy. This report
      should broaden the radiographic differential diagnosis when seeking an
      explanation for the signs and symptoms of cervical myelopathy.

PMID- 11242398
TI  - Cervical disc prosthesis in humans: first failure.
AB  - STUDY DESIGN: Prospective preliminary trial of a cervical disc prosthesis.
      OBJECTIVE: To study the feasibility, efficacy in maintaining intervertebral
      mobility, and complications of a low-profile disc prosthesis implanted after
      single-level cervical discectomy. SUMMARY OF BACKGROUND DATA: Since studies
      reported by Baba et al, there is fear that degeneration of the intervertebral
      disc levels adjacent to cervical arthrodesis may be exacerbated by this
      arthrodesis. For this reason, several cervical prostheses have been designed as
      an alternative to arthrodesis. None of these prostheses, some of which are bulky,
      has been shown to be efficacious. METHODS: Five women and five men (average age,
      36 years) underwent implantation of the present disc prosthesis after single
      level discectomy. The discectomy was performed for cervical disc herniation that
      resulted in cervicobrachial pain for more than 3 months. None of the patients
      exhibited intervertebral instability on bending films. Preoperative magnetic
      resonance studies showed a noncontained disc herniation in all 10 patients and
      osteophytes in 2 of the patients. RESULTS: The cervicobrachial pain resolved in
      all 10 patients. Intense neck pain developed in 1 patient who underwent revision
      surgery to remove the prosthesis and perform an arthrodesis. Another patient
      developed neck pain but refused the proposed revision operation. Bending films
      showed mobility of the intervertebral space containing the prosthesis in both of
      these patients. In the 8 patients who remained pain free after the operation,
      lateral bending films at follow-up found no mobility of the implanted disc level.
      Five of these eight patients had circumferential fusion, 2 had posterior fusion,
      and 1 had anterior fusion. CONCLUSION: This prosthesis failed to achieve the
      desired effect because the intended mobility failed to persist in 8 of the 10
      patients and pain developed in the other 2 patients, in whom the mobility
      persisted.

PMID- 11242399
TI  - Nomenclature and classification of lumbar disc pathology. Recommendations of the
      Combined task Forces of the North American Spine Society, American Society of
      Spine Radiology, and American Society of Neuroradiology.

PMID- 11242401
TI  - A piece of my mind: from the foot of the gurney.

PMID- 11242403
TI  - Beta-lactam antibiotic and beta-lactamase inhibitor combinations.

PMID- 11242404
TI  - European concern over BSE transmission.

PMID- 11242405
TI  - Mental health agenda now set for US children.

PMID- 11242406
TI  - Breast cancer prevention study aims to overcome drug bias.

PMID- 11242411
TI  - Cost-effectiveness of colorectal cancer screening.

PMID- 11242412
TI  - Cost-effectiveness of colorectal cancer screening.

PMID- 11242413
TI  - Cost-effectiveness of colorectal cancer screening.

PMID- 11242415
TI  - Drug dependence as a chronic medical illness.

PMID- 11242417
TI  - Dextromethorphan and ecstasy pills.

PMID- 11242419
TI  - Health insurance status of recent US immigrants.

PMID- 11242421
TI  - Overpopulation as a public health challenge.

PMID- 11242422
TI  - Overpopulation as a public health challenge.

PMID- 11242424
TI  - The pills identification test: a tool to assess adherence to antiretroviral
      therapy.

PMID- 11242425
TI  - Promotion of Breastfeeding Intervention Trial (PROBIT): a randomized trial in the
      Republic of Belarus.
AB  - CONTEXT: Current evidence that breastfeeding is beneficial for infant and child
      health is based exclusively on observational studies. Potential sources of bias
      in such studies have led to doubts about the magnitude of these health benefits
      in industrialized countries. OBJECTIVE: To assess the effects of breastfeeding
      promotion on breastfeeding duration and exclusivity and gastrointestinal and
      respiratory infection and atopic eczema among infants. DESIGN: The Promotion of
      Breastfeeding Intervention Trial (PROBIT), a cluster-randomized trial conducted
      June 1996-December 1997 with a 1-year follow-up. SETTING: Thirty-one maternity
      hospitals and polyclinics in the Republic of Belarus. PARTICIPANTS: A total of 17
      046 mother-infant pairs consisting of full-term singleton infants weighing at
      least 2500 g and their healthy mothers who intended to breastfeed, 16491 (96.7%)
      of which completed the entire 12 months of follow-up. INTERVENTIONS: Sites were
      randomly assigned to receive an experimental intervention (n = 16) modeled on the
      Baby-Friendly Hospital Initiative of the World Health Organization and United
      Nations Children's Fund, which emphasizes health care worker assistance with
      initiating and maintaining breastfeeding and lactation and postnatal
      breastfeeding support, or a control intervention (n = 15) of continuing usual
      infant feeding practices and policies. MAIN OUTCOME MEASURES: Duration of any
      breastfeeding, prevalence of predominant and exclusive breastfeeding at 3 and 6
      months of life and occurrence of 1 or more episodes of gastrointestinal tract
      infection, 2 or more episodes of respiratory tract infection, and atopic eczema
      during the first 12 months of life, compared between the intervention and control
      groups. RESULTS: Infants from the intervention sites were significantly more
      likely than control infants to be breastfed to any degree at 12 months (19.7% vs
      11.4%; adjusted odds ratio [OR], 0.47; 95% confidence interval [CI], 0.32-0.69),
      were more likely to be exclusively breastfed at 3 months (43.3% vs 6.4%; P<.001)
      and at 6 months (7.9% vs 0.6%; P =.01), and had a significant reduction in the
      risk of 1 or more gastrointestinal tract infections (9.1% vs 13.2%; adjusted OR,
      0.60; 95% CI, 0.40-0.91) and of atopic eczema (3.3% vs 6.3%; adjusted OR, 0.54;
      95% CI, 0.31-0.95), but no significant reduction in respiratory tract infection
      (intervention group, 39.2%; control group, 39.4%; adjusted OR, 0.87; 95% CI, 0.59
      1.28). CONCLUSIONS: Our experimental intervention increased the duration and
      degree (exclusivity) of breastfeeding and decreased the risk of gastrointestinal
      tract infection and atopic eczema in the first year of life. These results
      provide a solid scientific underpinning for future interventions to promote
      breastfeeding.

PMID- 11242426
TI  - Adverse events associated with prescription drug cost-sharing among poor and
      elderly persons.
AB  - CONTEXT: Rising costs of medications and inequities in access have sparked calls
      for drug policy reform in the United States and Canada. Control of drug
      expenditures by prescription cost-sharing for elderly persons and poor persons is
      a contentious issue because little is known about the health impact in these
      subgroups. OBJECTIVES: To determine (1) the impact of introducing prescription
      drug cost-sharing on use of essential and less essential drugs among elderly
      persons and welfare recipients and (2) rates of emergency department (ED) visits
      and serious adverse events associated with reductions in drug use before and
      after policy implementation. DESIGN AND SETTING: Interrupted time-series analysis
      of data from 32 months before and 17 months after introduction of a prescription
      coinsurance and deductible cost-sharing policy in Quebec in 1996. Separate 10
      month prepolicy control and postpolicy cohort studies were conducted to estimate
      the impact of the drug reform on adverse events. PARTICIPANTS: A random sample of
      93 950 elderly persons and 55 333 adult welfare medication recipients. MAIN
      OUTCOME MEASURES: Mean daily number of essential and less essential drugs used
      per month, ED visits, and serious adverse events (hospitalization, nursing home
      admission, and mortality) before and after policy introduction. RESULTS: After
      cost-sharing was introduced, use of essential drugs decreased by 9.12% (95%
      confidence interval [CI], 8.7%-9.6%) in elderly persons and by 14.42% (95% CI,
      13.3%-15.6%) in welfare recipients; use of less essential drugs decreased by
      15.14% (95% CI, 14.4%-15.9%) and 22.39% (95% CI, 20.9%-23.9%), respectively. The
      rate (per 10 000 person-months) of serious adverse events associated with
      reductions in use of essential drugs increased from 5.8 in the prepolicy control
      cohort to 12.6 in the postpolicy cohort in elderly persons (a net increase of 6.8
      [95% CI, 5.6-8.0]) and from 14.7 to 27.6 in welfare recipients (a net increase of
      12.9 [95% CI, 10.2-15.5]). Emergency department visit rates related to reductions
      in the use of essential drugs also increased by 14.2 (95% CI, 8.5-19.9) per 10
      000 person-months in elderly persons (prepolicy control cohort, 32.9; postpolicy
      cohort, 47.1) and by 54.2 (95% CI, 33.5-74.8) among welfare recipients (prepolicy
      control cohort, 69.6; postpolicy cohort, 123.8). These increases were primarily
      due to an increase in the proportion of recipients who reduced their use of
      essential drugs. Reductions in the use of less essential drugs were not
      associated with an increase in risk of adverse events or ED visits. CONCLUSIONS:
      In our study, increased cost-sharing for prescription drugs in elderly persons
      and welfare recipients was followed by reductions in use of essential drugs and a
      higher rate of serious adverse events and ED visits associated with these
      reductions.

PMID- 11242427
TI  - Early statin treatment following acute myocardial infarction and 1-year survival.
AB  - CONTEXT: Randomized trials have established statin treatment as secondary
      prevention in coronary artery disease, but it is unclear whether early treatment
      with statins following acute myocardial infarction (AMI) influences survival.
      OBJECTIVE: To evaluate the association between statin treatment initiated before
      or at the time of hospital discharge and 1-year mortality after AMI. DESIGN AND
      SETTING: Prospective cohort study using data from the Swedish Register of Cardiac
      Intensive Care on patients admitted to the coronary care units of 58 Swedish
      hospitals in 1995-1998. One-year mortality data were obtained from the Swedish
      National Cause of Death Register. PATIENTS: Patients with first registry-recorded
      AMI who were younger than 80 years and who were discharged alive from the
      hospital, including 5528 who received statins at or before discharge and 14 071
      who did not. MAIN OUTCOME MEASURE: Relative risk of 1-year mortality according to
      statin treatment. RESULTS: At 1 year, unadjusted mortality was 9.3% (1307 deaths)
      in the no-statin group and 4.0% (219 deaths) in the statin treatment group. In
      regression analysis adjusting for confounding factors and propensity score for
      statin use, early statin treatment was associated with a reduction in 1-year
      mortality (relative risk, 0.75; 95% confidence interval, 0.63-0.89; P =.001) in
      hospital survivors of AMI. This reduction in mortality was similar among all
      subgroups based on age, sex, baseline characteristics, previous disease
      manifestations, and medications. CONCLUSIONS: Early initiation of statin
      treatment in patients with AMI is associated with reduced 1-year mortality. These
      results emphasize the importance of implementing the results of randomized statin
      trials in unselected AMI patients.

PMID- 11242428
TI  - Completeness of safety reporting in randomized trials: an evaluation of 7 medical
      areas.
AB  - CONTEXT: Randomized trials with adequate sample size offer an opportunity to
      assess the safety of new medications in a controlled setting; however,
      generalizable data on drug safety reporting are sparse. OBJECTIVE: To scrutinize
      the completeness of safety reporting in randomized trials. DESIGN, SETTING, AND
      PATIENTS: Survey of safety reporting in 192 randomized drug trials 7 diverse
      topics with sample sizes of at least 100 patients and at least 50 patients in a
      study arm (N = 130074 patients). Trial reports were identified from comprehensive
      meta-analyses in 7 medical areas. MAIN OUTCOME MEASURES: Adequate reporting of
      specific adverse effects and frequency and reasons for withdrawals due to toxic
      effects; article space allocated to safety reporting and predictors of such
      reporting. RESULTS: Severity of clinical adverse effects and laboratory
      determined toxicity was adequately defined in only 39% and 29% of trial reports,
      respectively. Only 46% of trials stated the frequency of specific reasons for
      discontinuation of study treatment due to toxicity. For these 3 parameters, there
      was significant heterogeneity in rates of adequate reporting across topics (P
      =.003, P<.001, and P =.02, respectively). Overall, the median space allocated to
      safety results was 0.3 page. A similar amount of space was devoted to contributor
      names and affiliations (P =.16). On average, the percentage of space devoted to
      safety in the results section was 9.3% larger in trials involving dose
      comparisons than in those that did not (P<.001) and 3.8% smaller in trials
      reporting statistically significant results for efficacy outcomes (P =.047).
      CONCLUSIONS: The quality and quantity of safety reporting vary across medical
      areas, study designs, and settings but they are largely inadequate. Current
      standards for safety reporting in randomized trials should be revised to address
      this inadequacy.

PMID- 11242429
TI  - Safety outcomes in meta-analyses of phase 2 vs phase 3 randomized trials:
      Intracranial hemorrhage in trials of bolus thrombolytic therapy.
AB  - CONTEXT: Recent studies have reported disagreement between meta-analysis of small
      trials and subsequent large trials addressing the same question. However,
      disagreement for uncommon but serious adverse safety outcomes has not been
      examined. OBJECTIVE: To explore disagreement for serious adverse safety
      (intracranial hemorrhage [ICH]) and efficacy outcomes between meta-analysis of
      phase 2 (small) vs meta-analysis of phase 3 (large) randomized controlled trials
      comparing the efficacy of bolus thrombolytic therapy with infusion for acute
      myocardial infarction (AMI). DATA SOURCES: Electronic databases (MEDLINE,
      Cochrane Database of Clinical Trials) between January 1980 and December 1999
      using the search terms thrombolysis, thrombolytic therapy, and myocardial
      infarction; conference proceedings; and reference lists. STUDY SELECTION: Fifteen
      randomized trials comparing thrombolytic agents administered by bolus injection
      with standard infusion therapy in patients with AMI. DATA EXTRACTION: Data on
      ICH, other causes of stroke, total mortality, and reinfarction were independently
      extracted from each study by 2 observers. DATA SYNTHESIS: Meta-analysis of 9
      phase 2 trials (n = 3956) revealed a lower risk of ICH with bolus thrombolytic
      therapy (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.27-1.01), which
      was not statistically significant. Meta-analysis of 6 phase 3 trials (n = 62 673)
      indicated a significant increase in risk of ICH (OR, 1.25; 95% CI, 1.06-1.49).
      These results were significantly different (P =.01). There was no disagreement
      for efficacy outcomes. Phase 2 trials included younger and heavier patients with
      lower baseline blood pressures, and were more often open-label. Subgroup analyses
      suggested that each of these factors was associated with a lower estimate of risk
      of ICH with bolus agents. CONCLUSIONS: Our results suggest that when therapeutic
      interventions are associated with a potential for uncommon but serious adverse
      safety outcomes, there may be differences between small phase 2 and large phase 3
      trials that result in their disagreement for safety but not necessarily efficacy
      outcomes. Further investigation of the frequency and causes of disagreement
      between small and large trials for safety outcomes is warranted.

PMID- 11242430
TI  - Evaluation of a risk assessment questionnaire used to target tuberculin skin
      testing in children.
AB  - CONTEXT: Universal tuberculin skin testing of children has been shown to be
      costly and inefficient. In response, several authorities have recommended
      targeted screening based on epidemiological risk. In 1996, the New York City
      Department of Health (NYCDOH) developed questions to identify children who
      require a tuberculin skin test. OBJECTIVE: To determine the sensitivity,
      specificity, and predictive validity of the NYCDOH tuberculosis risk assessment
      questionnaire. DESIGN: Prospective criterion standard study in which tuberculin
      skin tests and the NYCDOH questionnaire were administered simultaneously between
      August 1996 and January 1998. Specific questions asked about contact with a
      tuberculosis case, birth in or travel to endemic areas, regular contact with high
      risk adults, and human immunodeficiency virus infection in the child. SETTING:
      Ambulatory clinic in South Bronx, New York, NY. PARTICIPANTS: Consecutive sample
      of 2920 children aged 1 to 18 years. MAIN OUTCOME MEASURES: Sensitivity,
      specificity, positive and negative predictive values of the questionnaire, and
      odds ratio (OR) of reactive skin test results. RESULTS: The NYCDOH questionnaire
      identified 413 children (14%) as having at least 1 risk factor. Of these, 23
      (5.6%) had a positive skin test result; 4 (0.16%) of the 2507 without risk
      factors had a positive result. Results for the full NYCDOH questionnaire were
      sensitivity, 85.2%; specificity, 86.0%; negative predictive value, 99.8%;
      positive predictive value, 5.4%; and OR, 35.2 (95% confidence interval, 12.1
      102.4). CONCLUSION: The NYCDOH questionnaire is a valid instrument for
      identifying children for tuberculin skin testing.

PMID- 11242431
TI  - A 25-year-old woman with bipolar disorder.

PMID- 11242432
TI  - A 48-year-old man with recurrent sinusitis, 1 year later.

PMID- 11242434
TI  - Jama 2001 medical education issue: a call for papers.

PMID- 11242433
TI  - Breastfeeding in Belarus.

PMID- 11242440
TI  - Effects of milk-derived bioactives: an overview.
AB  - Milk contains various components with physiological functionality. Peptides
      derived from caseins and whey proteins including opioid peptides,
      antihypertensive peptides, casein phosphopeptides, alpha- and beta-lactorphins
      and albutensin have been shown to possess various bioactive properties. This
      review considers an overview of the bioactive components in milk proteins and
      whey and their physiological function.

PMID- 11242441
TI  - Occurrence, structure, biochemical properties and technological characteristics
      of lactoferrin.
AB  - The structure of the iron-binding glycoprotein lactoferrin, present in milk and
      other exocrine secretions, has been elucidated in great detail, both the three
      dimensional protein structure and the attached N-glycans. Structure-function
      relationships are being established. From these studies a function for
      lactoferrin in host defence and modulation of iron metabolism emerges. This paper
      describes in some detail how iron and other cations may be bound by lactoferrins
      from human or bovine sources and elucidates parts of the molecule that are
      critical for interactions with cells and biomolecules. Furthermore, the
      technological aspects, more specifically the heat-sensitivity, of bovine
      lactoferrin in different matrices are described.

PMID- 11242442
TI  - Lactoperoxidase: physico-chemical properties, occurrence, mechanism of action and
      applications.
AB  - Lactoperoxidase (LP) is one of the most prominent enzymes in bovine milk and
      catalyses the inactivation of a wide range of micro-organisms in the
      lactoperoxidase system (LP-s). LP-systems are also identified as natural
      antimicrobial systems in human secretions such as saliva, tear-fluid and milk and
      are found to be harmless to mammalian cells. The detailed molecular structure of
      LP is identified and the major products generated by the LP-s and their
      antimicrobial action have been elucidated for the greater part. In this paper
      several aspects of bovine LP and LP-s are discussed, including physico-chemical
      properties, occurrence in milk and colostrum and mechanisms of action. Since the
      introduction of industrial processes for the isolation of LP from milk and whey
      the interest in this enzyme has increased considerably and attention will be paid
      to potential and actual applications of LP-systems as biopreservatives in food
      and other products.

PMID- 11242444
TI  - Milk protein-derived peptide inhibitors of angiotensin-I-converting enzyme.
AB  - Numerous casein and whey protein-derived angiotensin-I-converting enzyme (ACE)
      inhibitory peptides/hydrolysates have been identified. Clinical trials in
      hypertensive animals and humans show that these peptides/hydrolysates can bring
      about a significant reduction in hypertension. These peptides/hydrolysates may be
      classified as functional food ingredients and nutraceuticals due to their ability
      to provide health benefits i.e. as functional food ingredients in reducing the
      risk of developing a disease and as nutraceuticals in the prevention/treatment of
      disease.

PMID- 11242443
TI  - Opioid peptides encrypted in intact milk protein sequences.
AB  - Opioid agonistic and antagonistic peptides which are inactive within the sequence
      of the precursor milk proteins can be released and thus activated by enzymatic
      proteolysis, for example during gastrointestinal digestion or during food
      processing. Activated opioid peptides are potential modulators of various
      regulatory processes in the body. Opioid peptides can interact with subepithelial
      opioid receptors or specific luminal binding sites in the intestinal tract.
      Furthermore, they may be absorbed and then reach endogenous opioid receptors.

PMID- 11242445
TI  - Biological activities of bovine glycomacropeptide.
AB  - Biological activity of bovine kappa-caseino glycomacropeptide (GMP) has received
      much attention in recent years. Research has focused on the ability of GMP to
      bind cholera and Escherichia coli enterotoxins, inhibit bacterial and viral
      adhesion, suppress gastric secretions, promote bifidobacterial growth and
      modulate immune system responses. Of these, protection against toxins, bacteria,
      and viruses and modulation of the immune system are the most promising
      applications.

PMID- 11242446
TI  - Occurrence and biochemical characteristics of natural bioactive substances in
      bovine milk lipids.
AB  - Bovine milk lipids (BML) contain a number of bioactive substances with positive
      as well as negative properties, mainly in the class of fatty acids. Besides trans
      fatty acids (TFA), conjugated linoleic acids (CLA) are of particular interest.
      Apart from ruminant meat products the main source of CLA in food are BML.
      Although TFA as well as saturated fatty acids (12:0-16:0) are thought to be
      positively correlated with atherosclerosis and coronary heart disease, CLA are
      considered antiatherogenic. Further, CLA are reported to reduce adipose fat and
      to have anticarcinogenic properties. The varying CLA and TFA contents of lipids
      from milk and dairy products are positively correlated with one another. However,
      TFA are also negatively correlated with 12:0-16:0 in BML. Anticarcinogenic
      effects are also ascribed to butyric acid as well as to some phospholipids and
      ether lipids present in BML. Moreover, the essential fatty acids 18:2n-6 and
      18:3n-3 are found in BML which are involved in a variety of biochemical processes
      and thus have numerous functions in human metabolism. Contents of the individual
      bioactive components of BML are summarised taking into account also seasonal
      variations. The total content of bioactive substances in BML is approximately 75
      % but their overall impact on human health considering benefits and drawbacks is
      difficult to assess.

PMID- 11242447
TI  - Polyamines in human and animal milk.
AB  - Polyamines are highly regulated polycations which are essentially involved in
      cell growth and differentiation. Polyamines in food significantly contribute to
      the polyamine body pool. Dietary polyamines exert various direct and indirect
      trophic effects on the rat's immature intestine and play an important role during
      intestinal maturation. Human milk and that of other mammalians contain relatively
      high levels of polyamines which are essential luminal growth and maturation
      factors. The polyamines spermidine and spermine as well as their diamine
      precursor putrescine are ubiquitous normal constituents of all prokaryotic and
      eukaryotic cells and are essentially involved in various processes of cell growth
      and differentiation (Pegg & McCann, 1982; Tabor & Tabor, 1984; Seiler, 1990).

PMID- 11242448
TI  - Nucleosides and nucleotides: natural bioactive substances in milk and colostrum.
AB  - Nucleotides, nucleosides and nucleobases belong to the non-protein-nitrogen (NPN)
      fraction of milk. The largest amounts of ribonucleosides and ribonucleotides-
      ribose forms only were considered in this review--were measured directly after
      parturition in bovine milk and other ruminants as well as in the milk of humans.
      Generally, concentrations of most of the nucleos(t)ides tend to decrease
      gradually with advancing lactation period or nursing time. The species-specific
      pattern of these minor constituents in milk from different mammals is a
      remarkable property and confirms, at least, the specific physiological impact of
      these minor compounds in early life. The physiological capacity of these
      compounds in milk is given by the total potentially available nucleosides. The
      main dietary sources of nucleos(t)ides are nucleoproteins and nucleic acids which
      are converted in the course of intestinal digestion into nucleosides and
      nucleobases the preferred forms for absorption in the intestine. Thus,
      nucleosides and nucleobases are suggested to be the acting components of dietary
      and/or supplemented nucleic acid-related compounds in the gut. They are used by
      the body as exogenous trophochemical sources and can be important for optimal
      metabolic functions. Up to 15 % of the total daily need for a breast-fed infant
      was calculated to come from this dietary source. Concerning their biological role
      they not only act as metabolites but are also involved as bioactive substances in
      the regulation of body functions. Dietary nucleotides affect immune modulation,
      e.g. they enhance antibody responses of infants as shown by a study with more
      than 300 full-term healthy infants. Dietary nucleos(t)ides are found to
      contribute to iron absorption in the gut and to influence desaturation and
      elongation rates in fatty acid synthesis, in particular long-chain
      polyunsaturated fatty acids in early stages of life. The in vitro modulation of
      cell proliferation and apoptosis has been described by ribonucleosides, in
      particular by modified components using human cell culture models. Due to the bio
      and trophochemical properties of dietary nucleos(t)ides, the European Commission
      has allowed the use of supplementation with specific ribonucleotides in the
      manufacture of infant and follow-on formula. From the technochemical point of
      view, the ribonucleoside pattern is influenced by thermal treatment of milk. In
      addition ribonucleosides are useful indicators for quantifying adulterations of
      milk and milk products.

PMID- 11242449
TI  - Oligosaccharides and glycoconjugates in bovine milk and colostrum.
AB  - Oligosaccharides and glycoconjugates are some of the most important bioactive
      components in milk. A great deal of information is available on the biological
      function of the components from human milk. Their primary role seems to be in
      providing protection against pathogens by acting as competitive inhibitors for
      the binding sites on the epithelial surfaces of the intestine. Evidence is also
      available to support the role of some of these components as growth promoters for
      genera of beneficial microflora in the colon. Compared with human milk, levels of
      oligosaccharides in bovine milk are very low. Nevertheless, a number of neutral
      and acidic oligosaccharides have been isolated from bovine milk and
      characterised. The highest concentration of these molecules is found in early
      postparturition milk (colostrum). The chemical structure of the oligosaccharides
      and many of the glycoconjugates from bovine milk are similar to those in human
      milk. It is likely that bovine oligosaccharides and glycoconjugates can be used
      in milk products as bioactive components in human nutrition.

PMID- 11242450
TI  - Milk immunoglobulins and complement factors.
AB  - The importance of colostrum for the growth and health of newborn offspring is
      well known. In bovine colostrum, the antibody (immunoglobulin) complement system
      provides a major antimicrobial effect against a wide range of microbes and
      confers passive immunity until the calf's own immune system has matured. Bovine
      serum and lacteal secretions contain three major classes of immunoglobulins: IgG,
      IgM and IgA. The immunoglobulins are selectively transported from the serum into
      the mammary gland, as a result of which the first colostrum contains very high
      concentrations of immunoglobulins (40-200 mg/ml). IgG1 accounts for over 75 % of
      the immunoglobulins in colostral whey, followed by IgM, IgA and IgG2. All these
      immunoglobulins decrease within a few days to a total immunoglobulin
      concentration of 0.7-1.0 mg/ml, with IgG1 representing the major Ig class in milk
      throughout the lactation period. Together with the antibodies absorbed from
      colostrum after birth, the complement system plays a crucial role in the passive
      immunisation of the newborn calf. The occurrence of haemolytic or bactericidal
      complement activity in bovine colostrum and milk has been demonstrated in several
      studies. This review deals with the characteristics of bovine Igs and the
      complement system to be exploited as potential ingredients for health-promoting
      functional foods.

PMID- 11242451
TI  - Immunomodulatory properties of milk.
AB  - There is increasing commercial interest in the production of functional
      foodstuffs which have health-promoting properties. Over the last five to ten
      years, significant progress has been made in the identification and
      characterisation of bovine milk components that can affect the function of the
      immune system. This review outlines the major components of bovine milk that have
      been shown to modulate immune function, and discusses experimental approaches to
      the identification of various facets of the immune response that are known to be
      affected by milk-derived proteins.

PMID- 11242452
TI  - Mineral-binding milk proteins and peptides; occurrence, biochemical and
      technological characteristics.
AB  - Minerals and trace elements in cow's milk occur as inorganic ions and salts or
      form complexes with proteins and peptides, carbohydrates, fats and small
      molecules. The main mineral binder or chelators of calcium are the caseins,
      alphas1-casein, alphas2-casein, beta-casein and kappa-casein, but also whey
      proteins and lactoferrin bind specific minerals like calcium, magnesium, zinc,
      iron, sodium and potassium. Less documented is the binding of trace elements.
      Peptides obtained by in vitro or in vivo hydrolysis act as mineral trappers
      through specific and non-specific binding sites. They may then function as
      carriers, chelators, of various minerals and thus enhance or inhibit
      bioavailability. Peptides from milk proteins have found interesting new
      applications in the food industry as products with improved functionality or as
      ingredients of dietary products, or used in pharmaceutical industry.
      Fortification of foods with minerals in a low concentration has for a long time
      been used in some countries to overcome mineral deficiency, which is an
      increasing problem in humans. These types of foods are being used to create a new
      generation of super foods in the industry today.

PMID- 11242453
TI  - Peptides affecting coagulation.
AB  - Based on amino acid sequence similarities that exist between the fibrinogen gamma
      chain and kappa-casein, and also functional similarities between milk and blood
      coagulation, considerable effort has been made to investigate the effects of milk
      proteins and peptides on platelet function and thrombosis. In particular, a
      number of peptides derived from the glycomacropeptide segment of kappa-casein,
      have been shown to inhibit platelet aggregation and thrombosis. KRDS, a peptide
      from lactoferrin has also been shown to inhibit platelet aggregation but to a
      lesser extent than its fibrinogen analogue RGDS. Despite their functional and
      structural similarities they do not act in the same way on platelet function and
      are thought to affect thrombus formation differently. Further investigation is
      needed to determine if these milk-derived bioactive peptides are released
      naturally following ingestion and might therefore be useful as the basis for milk
      based products with anti-thrombotic properties.

PMID- 11242454
TI  - Antioxidative factors in milk.
AB  - Lipid auto-oxidation in milk is affected by a complex interplay of pro- and
      antioxidants. Several of these compounds are also important nutrients in the
      human diet and may have other physiological effects in the gastrointestinal tract
      and other tissues. Among antioxidative enzymes superoxide dismutase catalyses the
      dismutation of superoxide anion to hydrogen peroxide. The degradation of hydrogen
      peroxide can be catalysed by catalase and the selenoprotein glutathione
      peroxidase. The latter enzyme can also degrade lipid peroxides. Lactoferrin may
      have an important role by binding pro-oxidative iron ions. The occurrence of
      different forms of these antioxidative proteins in milk and available data on
      their functional role are reviewed. More remains to be learnt of individual
      compounds and as an example the potential role of seleno compounds in milk is
      virtually unknown. Antioxidative vitamins in milk can provide an important
      contribution to the daily dietary intake. Moreover vitamin E and carotenoids act
      as fat-soluble antioxidants, e.g. in the milk fat globule membrane, which is
      regarded as a major site of auto-oxidation. Vitamin C is an important water
      soluble antioxidant and interacts in a complex manner with iron and fat-soluble
      antioxidants. The concentrations of these compounds in milk are affected by cow
      feeding rations and milk storage conditions. Since milk contains a number of
      antioxidants many reactions are possible and the specific function of each
      antioxidant cannot easily be defined. There are indications that other compounds
      may have antioxidative function and measurement of total antioxidative capacity
      should be a useful tool in evaluating their relative roles.

PMID- 11242455
TI  - Immunoregulatory peptides in bovine milk.
AB  - Bovine milk is known to contain a number of peptide fractions that can affect
      immune function. The vast majority of immunoregulatory peptides that have been
      characterised are hydrolysate derivatives of major milk proteins. Recent research
      has also indicated that the metabolic activity of probiotic lactic acid bacteria
      can generate de novo immunoregulatory peptides from milk, via enzymatic
      degradation of parent milk protein molecules. In contrast, relatively little is
      known of endogenous, preformed immunoregulatory peptides in milk that may be
      relevant to modulating human health. The natural in vivo role of preformed and
      enzymatically derived peptides is likely to be one of regulation of the neonatal
      (bovine) gastrointestinal tract immune system, in order to modulate immune
      function with respect to the development of immunocompetence and avoidance of
      undesirable immunological responses (e.g. tolerance, and hypersensitivity to
      nutrients). There is scope for the further characterisation of both the origin
      and function of milk-derived immunoregulatory peptides, so that their potential
      to influence human health can be fully appraised. This review highlights our
      current knowledge of milk-derived immunoregulatory peptides, and outlines areas
      that are of relevance for further research.

PMID- 11242456
TI  - Natural bioactive substances in milk and colostrum: effects on the arterial blood
      pressure system.
AB  - High blood pressure is a significant public health problem worldwide which is
      associated with increased risk of cardiovascular disease, stroke, and renal
      disease. The development of this disease is influenced by genetic and
      environmental factors. The results of many studies have linked increased
      consumption of milk and milk products with lower blood pressure and reduced risk
      of hypertension. The intake of several minerals found in milk has been
      demonstrated to have an inverse relationship with blood pressure. Peptides formed
      during the digestion of milk proteins have also been demonstrated to have a blood
      pressure lowering effect. Other components in milk that have been examined for
      their effects on blood pressure have been less promising. More recent data
      indicate that a dietary pattern that is low in fat, with fruits, vegetables, and
      low fat dairy products can significantly reduce blood pressure and lower risk of
      developing high blood pressure.

PMID- 11242457
TI  - In vivo antimicrobial and antiviral activity of components in bovine milk and
      colostrum involved in non-specific defence.
AB  - The in vivo evidence of the antimicrobial and antiviral activity of bovine milk
      and colostrum derived components are reviewed with special emphasis on
      lactoferrin and lactoperoxidase. Their mode of action and the rationale for their
      application in efficacy trials with rodents, farm animals, fish and humans, to
      give protection against infectious agents, are described. A distinction is made
      between efficacy obtained by oral and non-oral administration of these non
      specific defence factors which can be commercially applied in large quantities
      due to major achievements in dairy technology. From the in vivo studies one can
      infer that lactoferrin and lactoperoxidase are very promising, naturally
      occurring antimicrobials for use in fish farming, husbandry, oral hygiene and
      functional foods. Other promising milk-derived compounds include lipids, from
      which anti-infective degradation products are generated during digestion, and
      antimicrobial peptides hidden in the casein molecules.

PMID- 11242458
TI  - Bovine milk antibodies for health.
AB  - The immunoglobulins of bovine colostrum provide the major antimicrobial
      protection against microbial infections and confer a passive immunity to the
      newborn calf until its own immune system matures. The concentration in colostrum
      of specific antibodies against pathogens can be raised by immunising cows with
      these pathogens or their antigens. Immune milk products are preparations made of
      such hyperimmune colostrum or antibodies enriched from it. These preparations can
      be used to give effective specific protection against different enteric diseases
      in calves and suckling pigs. Colostral immunoglobulin supplements designed for
      farm animals are commercially available in many countries. Also, some immune milk
      products containing specific antibodies against certain pathogens have been
      launched on the market. A number of clinical studies are currently in progress to
      evaluate the efficacy of immune milks in the prevention and treatment of various
      human infections, including those caused by antibiotic resistant bacteria. Bovine
      colostrum-based immune milk products have proven effective in prophylaxis against
      various infectious diseases in humans. Good results have been obtained with
      products targeted against rotavirus, Shigella flexneri, Escherichia coli,
      Clostridium difficile, Streptococcus mutans, Cryptosporidium parvum and
      Helicobacter pylori. Some successful attempts have been made to use immune milk
      in balancing gastrointestinal microbial flora. Immune milk products are promising
      examples of health-promoting functional foods, or nutraceuticals. This review
      summarises the recent progress in the development of these products and evaluates
      their potential as dietary supplements and in clinical nutrition.

PMID- 11242459
TI  - Effects of bioactive substances in milk on mineral and trace element metabolism
      with special reference to casein phosphopeptides.
AB  - Bioactivity of phosphopeptides yielded after tryptic hydrolysis of casein (CPP)
      was reported more than 50 years ago when CPP were found to improve calcium
      balance in rachitic newborns. Several investigations have been carried out to
      study the effects of CPP mainly on calcium metabolism but also on other minerals
      like iron and zinc. Most of the experiments were in vitro studies or short-term
      experiments like the effects of CPP after single meals or their effect on mineral
      disappearance from intestinal everted sac or ligated loop. Investigations on
      calcium balance were also mainly short term, i.e. 3-4 weeks, and mainly done in
      rats. A few experiments have been carried out in minipigs, an animal model that
      is closer to the human than the rat. Studies in human were rare and short term.
      To date a variety of other peptides have been isolated after enzymatic
      hydrolysis, and some have been investigated for bioactivity, with equivocal
      findings. Bioactivity of phosphopeptides seemed to be more obvious when
      investigations were done in vitro or short term. Results were less clear in
      metabolic balance studies, especially under physiological conditions. The
      composition of the basal diet, i.e. content of calcium and phytate, or the
      protein source had a significant impact on the effect of phosphopeptides. It was
      concluded that phosphopeptides revealed positive effects on mineral solubility
      and absorbability, and bone mineralisation under certain experimental conditions.
      Accordingly they could have a beneficial effect on bone health for some groups of
      the population.

PMID- 11242460
TI  - Bioactive substances in milk with properties decreasing risk of cardiovascular
      diseases.
AB  - Milk is often seen as a potential promotor of atherosclerosis and coronary heart
      disease because it is a source of cholesterol and saturated fatty acids. But
      there are several studies indicating that milk and milk products may not affect
      adversely blood lipids as would be predicted from its fat content and fat
      composition. There are even factors in milk and milk products which may actively
      protect from this condition by improving several risk factors. Calcium, bioactive
      peptides and as yet unidentified components in whole milk may protect from
      hypertension, and folic acid, vitamin B6 (pyridoxine) and B12 (cyanocobalamin) or
      other unidentified components of skim milk may contribute to low homocysteine
      levels. Conjugated linoleic acid may have hypolipidaemic and antioxidative and
      thus antiatherosclerotic properties. Epidemiological studies suggest that milk
      and milk products fit well into a healthy eating pattern emphasizing cereals and
      vegetables.

PMID- 11242461
TI  - Anticancer properties of bovine milk.
AB  - Improved means of cancer prevention and treatment remain key goals of global
      health programmes. This is particularly true in Western society, where the
      elderly represent a large proportion of the population, and where the likelihood
      of tumour development is compounded by risk factors such as poor fibre/high fat
      diets and environmental pollution. Dietary intervention represents an attractive,
      non-invasive means of providing anticancer preventative and therapeutic benefits
      to at-risk individuals. This review focuses on the evidence for anticancer
      properties of bovine milk and milk-derived components. Evidence of a role for
      whole milk constituents, as well as purified minor components, in combating
      tumorigenesis is outlined. Shortcomings in current studies are highlighted, and
      future opportunities for targeted research to characterize important anticancer
      properties of milk are discussed.

PMID- 11242463
TI  - Diet for health and longevity. Foreward.

PMID- 11242464
TI  - Preventing diabetes--applying pathophysiological and epidemiological evidence.
AB  - This is a review of research carried out in Japanese Americans that points
      towards possible approaches to prevention of type 2 diabetes mellitus. The
      natural history of type 2 diabetes usually includes both insulin resistance and
      beta-cell dysfunction. Insulin secretion may compensate for insulin resistance.
      Alternatively, enhanced insulin sensitivity may mask an insulin secretory defect.
      Epidemiological data support the view that in the vast majority of cases of type
      2 diabetes, insulin resistance is essential to the pathogenesis of hyperglycemia.
      Increased diabetes prevalence as ethnic groups migrate to more urban or
      westernized regions has been attributed to increased occurrence of insulin
      resistance. Research among Japanese Americans in Seattle, Washington, showed a
      higher prevalence of type 2 diabetes than in Japan, which suggested that factors
      associated with 'westernization' might be playing a role in bringing out
      underlying susceptibility to diabetes. Our research has shown that these
      impressions were correct and that the abnormalities that characterize the
      metabolic syndrome play a significant role. Due to increased intra-abdominal fat
      deposition, Japanese Americans were likely to be 'metabolically obese' despite
      relatively normal BMI. A diet higher in animal fat and lower levels of physical
      activity were risk factors leading to increased intra-abdominal fat deposition,
      insulin resistance, and diabetes. Information from epidemiological studies such
      as these may be used to determine whether diabetes may be prevented through
      changes in lifestyle or application of specific therapies targeted towards
      identified metabolic abnormalities.

PMID- 11242465
TI  - Early diagnosis, early treatment and the new diagnostic criteria of diabetes
      mellitus.
AB  - The main purpose of treating diabetes is to prevent chronic complications. Strict
      glycemic control is known to suppress the occurrence and progression of these
      complications. The test for plasma glucose is essential to identify diabetic
      patients, as mild hyperglycemia without symptoms can be a risk factor for
      complications. The new classification and diagnostic criteria for diabetes were
      proposed by the American Diabetes Association (ADA), WHO and Japan Diabetes
      Society (JDS) between 1997 and 1999. Diabetes is classified into four etiological
      categories; type 1, type 2, diabetes due to other specific mechanisms or
      conditions, and gestational diabetes. Another classification system according to
      the degree of metabolic abnormality has also been adopted. For diagnosis of
      diabetes, the JDS Committee classified the glycemic state into three categories
      based on fasting plasma glucose (FPG) and 2-h plasma glucose in the 75 g oral
      glucose tolerance test (2hPG); normal type (FPG <110 and 2hPG <140 mg/dl),
      diabetic type (FPG > or =126 and/or 2hPG > or =200 mg/dl), and borderline type
      (neither normal nor diabetic type). The borderline type corresponds to the sum of
      impaired fasting glycemia (IFG) and impaired glucose tolerance (IGT) based on ADA
      and WHO. Using the JDS criteria, diabetes is diagnosed when hyperglycemia of
      'diabetic type' is confirmed on two or more occasions. ADA recommends the use of
      FPG alone for the diagnosis of diabetes, but findings from both Japan and Europe
      indicate that many diabetic subjects would be classified as non-diabetic solely
      on the FPG test. JDS recommends the use of the glucose tolerance test when the
      elevation of FPG is mild. Keeping glycemia near-normal by periodic monitoring of
      glycemic parameters and by appropriate treatment would prevent or reduce the
      diabetic complications in patients to a minimum.

PMID- 11242466
TI  - Chronic complications in diabetes mellitus.
AB  - Diabetes mellitus is one of the most prevalent diseases among adult population in
      Japan. The persistent hyperglycemia is responsible for the appearance of various
      organ and tissue damage in diabetic subjects. Eyes, kidneys and peripheral nerves
      are frequently damaged due to diabetes-specific alteration in microvessels.
      Furthermore, large vessels are also damaged causing severe diseases such as
      myocardial infarction, cerebral infarction and gangrene. The pathogenesis of
      these alterations in small and large vessels has been extensively studied and
      various metabolic abnormalities induced by hyperglycemia are proposed to play a
      major role in the development of these diabetic vascular complications. Among
      those metabolic abnormalities, the activation of the diacyl glycerol-protein
      kinase C pathway has been proposed to play a pivotal role in the pathogenesis of
      not only microvascular complications but also macrovascular complications. The
      beneficial effect of a protein kinase C inhibitor on renal, retinal and
      atherosclerotic lesions in diabetic animal models may support this notion. The
      results of several large-scale clinical trials have confirmed the efficacy of
      glycemic control as well as blood pressure control in the management of diabetic
      complications. It is a prerequisite, therefore, to obtain near-normal glycemic
      and blood pressure control in order to prevent the appearance of diabetic
      complications and also suppress their progression. In this aspect nutritional
      consideration may be an important way to improve the quality of these
      managements.

PMID- 11242467
TI  - Diabetes and life-styles: role of physical exercise for primary prevention.
AB  - Regular physical exercise has been known to be beneficial in the treatment of
      type 2 diabetes. Epidemiological studies of physical exercise: previous non
      randomized studies suggested that a life-style intervention program involving
      diet and/or exercise reduced the progression of impaired glucose tolerance (IGT)
      to type 2 diabetes. Recent randomized controlled intervention trials also showed
      that diet and/or exercise intervention led to a significant decrease in the
      incidence of diabetes among those with IGT. Endocrinological and metabolic
      effects of exercise: in well controlled diabetic patients, physical exercise
      promotes utilization of blood glucose and lowers blood glucose levels. On the
      other hand, in poorly controlled diabetic patients with ketosis, physical
      exercise results in further rises in blood glucose, free fatty acids and ketone
      body concentrations. Long-term gentle regular jogging increases insulin action in
      respect of both carbohydrate and lipid metabolism despite no influence on body
      mass index or maximal oxygen uptake. A significant correlation was observed
      between deltaMCR (insulin sensitivity) and average daily steps Our recent data
      suggested that the improvement of insulin action by physical exercise was
      attributed, at least in part, to the increase in insulin-sensitive GLUT4 (glucose
      transporter 4) on the plasma membrane in skeletal muscle. In conclusion, as an
      adjunct to other forms of therapy, mild regular physical exercise will play an
      important role in primarily preventing type 2 diabetes.

PMID- 11242468
TI  - Diabetes mellitus and life-style--for the primary prevention of diabetes
      mellitus: the role of diet.
AB  - Diet treatment for diabetes requires restriction of the food amount (energy
      intake). It is desirable that patients have a proper relative consumption of the
      three main nutrients (proteins, carbohydrates, fats) and also habitually take low
      energy foods such as vegetables, mushrooms and seaweeds, etc. as often as
      possible in each meal. Therefore, we can replace the expression 'a diet for
      diabetes' with 'a diet for healthy living'. By showing a clinical case of an
      obese diabetic patient, who succeeded to reduce their body weight, HbA1c and oral
      agents through diet treatment, and finally could go on diet treatment only, the
      importance of diet therapy can be emphasized. Furthermore, the estimation index
      was examined to evaluate how accurately diabetic patients could estimate food
      energy. According to this study, a large amount of food on the plate leads most
      patients to underestimate the amount of real energy, and patients are apt to eat
      too much compared with having smaller amounts of food on the plate. By analyzing
      questionnaires on the diet therapy of approximately 3000 diabetics, it has been
      shown that the majority of patients at our hospital recognize that diet therapy
      is the most important factor in the treatment of diabetes. Interestingly,
      patients who ate all the food served showed a significantly higher body mass
      index compared with those who left served food.

PMID- 11242469
TI  - Nutrition in the Republic of Korea.
AB  - Until the 1970s, the Korean economy was dominantly agriculture, but nowadays,
      less than 10 % of the population lives in a rural area, and it is expected that
      within a generation the proportion of the population engaged in agriculture will
      be less than 5 %. The living standard is rising as the national economy benefits
      from the increased sale of industrial products. The dietary patterns are being
      changed. The diet has changed from one based predominantly on starch based food
      such as cereals or roots and vegetables to one in which animal products take
      great prominence with consequent increases in animal fat and protein. The move
      from simple unrefined foods to more refined and complex manufactured foods has
      become commonplace. As a result, the general nutritional situation has been
      improved. Such improvement, however, has brought about an increase in
      overnutrition in more affluent sections of the population, whereas dietary
      inadequacy among the lower socio-economic groups and vulnerable classes still
      persists. Overall, Korea suffers from both undernutrition and overnutrition. The
      national school feeding program started in 1953 after the Korean War with the
      support of UNICEF, CARE, and USAID as a relief food program and is now expanding
      successfully to a self-supporting nationwide scale. The applied nutrition project
      in rural areas introduced in 1967 with the support of UNICEF, FAO, WHO, and the
      Korean government continues successfully to the present day. A national dietary
      survey has been carried out once a year since 1969, and once every 3 years from
      1998. Korean recommended dietary allowances were established in 1962 and have
      been revised every 5 years. The government intends to establish national dietary
      guidelines for health promotion and prevention of chronic degenerative diseases.
      Nutrition education and research are also very important national undertakings.

PMID- 11242470
TI  - Epidemiological and nutritional research on prevention of cardiovascular disease
      in China.
AB  - Anthropological evidence suggests that regional differences in eating practices
      may be characterized by sub-ethnicity. Hakka is one sub-ethnicity who still
      retain a unique way of life in China. A field survey on diet and health among the
      Hakka people was undertaken in 1994. Approximately 200 participants were
      interviewed for their medical history, life-style and food habits. Blood
      pressure, body mass index, blood sample, 24 h urine and electrocardiogram were
      collected. The food samples taken from one tenth of the participants were
      analyzed for the ingredients in their daily meals. From this survey the
      prevalence of hypertension in Hakka was approximately 10 %. The sodium/potassium
      ratio was lower than that in Guangzhou and comparable with that in Okinawa, the
      island of longevity in Japan. For men, taurine level was found to be close to
      that in Mediterranean countries, where there is low mortality from cardiovascular
      diseases. For women, the taurine level was even higher, approximating that of
      Japanese women, who show the greatest longevity and lowest cardiac mortality
      worldwide. Less obesity was found in Hakka people than that in the US, Canada or
      Japan. These findings suggest that the following are the major reasons for these
      positive findings: the Hakka people maintain traditional food habits and maintain
      active awareness of their health; the major foods are rice, fish, vegetables and
      fruits; wide use of soybeans; extensive consumption of visceral organs which have
      rich source of trace elements. These eating practices and nutritional patterns
      may be beneficial factors for preventing atherosclerosis and hypertension.

PMID- 11242471
TI  - Mediterranean diet and longevity.
AB  - Mortality statistics from the WHO database covering the period 1960 to 1990 have
      provided intriguing evidence that something unusual has been affecting in a
      beneficial way the health of the Mediterranean population. In recent papers,
      which evaluated the evidence accumulated over the last three decades, it was
      concluded that the traditional Mediterranean diet meets several important
      criteria for a healthy diet. Direct evidence in support of the beneficial
      properties of the Mediterranean diet has also become available. These data were
      derived from three studies, which have used a diet score, devised a priori on the
      basis of eight desirable key features of the traditional common diet in the
      Mediterranean region. The conclusion of these studies is that a diet that adheres
      to the principles of the traditional Mediterranean one is associated with longer
      survival. The Greek version of the Mediterranean diet is dominated by the
      consumption of olive oil and by high consumption of vegetables and fruits.
      Antioxidants represent a common element in these foods and an antioxidant action
      provides a plausible explanation for the apparent benefits. Wild edible greens
      frequently eaten in rural Greece in the form of salads and pies contain very high
      quantities of flavonoids-- considerably higher than those found in red wine or
      black tea. While there is no direct evidence that these antioxidants are central
      to the benefits of the Mediterranean Diet, indirect evidence from epidemiological
      data and the increasing understanding of their mechanisms of action suggest that
      antioxidants may play a major role.

PMID- 11242473
TI  - Regulation of vitamin A metabolism-related gene expression.
AB  - Cellular retinol-binding protein, type II (CRBPII) is abundantly expressed in the
      small intestinal epithelial cells and plays a pivotal role in intestinal
      absorption and metabolism of retinol and beta-carotene. In the 5'-flanking region
      of rat CRBPII gene, two DR-1 type elements which consist of a direct repeat of
      the AGGTCA-like motif spaced by a single nucleotide have been identified as
      putative binding sites for a heterodimer of peroxisome proliferator-activated
      receptor (PPAR) and retinoid X-receptor (RXR). We found that CRBPII levels were
      elevated in the residual jejunal segment of rats subjected to jejunal bypass
      operation, where a concomitant increase in the apoprotein B levels occurred. This
      result suggested that CRBPII expression was enhanced by a condition where fat
      absorption was stimulated. Indeed, dietary fat (especially unsaturated fatty
      acids) has been shown to induce CRBPII gene expression in the jejunum. Nuclear
      run-on assays revealed that this increase of CRBPII mRNA levels by a high-fat
      diet was the result of the induction of the gene transcription through the rise
      in PPARalpha expression level as well as the increase in its ligand levels.
      Electrophoretic mobility shift assay using the DR-1 type cis-elements of CRBP II
      gene showed that PPARalpha-RXRalpha heterodimer was capable of binding to these
      elements, and that nuclear extracts from the jejunum of rats fed the high-fat
      diet gave greater density of retarded bands than those of rats fed a fat-free
      diet. We also found that the expression of PPARdelta was rather reduced by
      dietary fat. Thus, CRBPII gene expression is regulated predominantly by dietary
      fatty acids.

PMID- 11242472
TI  - Dietary strategies to reduce the burden of cancer and cardiovascular disease in
      the UK.
AB  - The importance attributed to dietary change as a means of helping to achieve the
      major goals of the UK's public health policy as articulated in the Health of the
      Nation White paper (Department of Health, 1992) is less apparent in the most
      recent strategy document (Department of Health, 1999). Greater emphasis is given
      to amelioration of the socio-economic circumstances that are believed to
      contribute to inequalities in health. Better understanding of the elements of
      foods and diets which help protect health together with better evidence of
      effective dietary interventions are essential if the opportunities to use diet to
      reduce the burden of non-communicable diseases are to be realised. This is likely
      to need new research strategies that take advantage of emerging information from
      genomics and proteomics to produce evidence of safety, efficacy and
      applicability. Ethical exploitation of the rapid growth in interest in
      'functional foods' by the food industry will require a level of investment in
      biomedical research unusual in the past.

PMID- 11242474
TI  - Peroxisome proliferator-activated receptor gamma, the ultimate liaison between
      fat and transcription.
AB  - The peroxisome proliferator-activated receptor gamma (PPARgamma) is nuclear
      receptor that controls the expression of a large number of genes involved in
      adipocyte differentiation, lipid storage and insulin sensitization. PPARgamma is
      bound and activated by fatty acid derivatives and prostaglandin J2. In addition,
      thiazolidinediones, non-steroidal anti-inflammatory drugs are synthetic ligands
      and agonists of this receptor. This review addresses the role of PPARgamma in
      obesity and diabetes.

PMID- 11242475
TI  - Molecular mechanism of transcriptional control by nuclear vitamin receptors.
AB  - Nuclear receptors for vitamins A and D belong to the nuclear hormone receptor
      superfamily and act as ligand-inducible transcription factors. Therefore, most of
      the biological actions of vitamins A and D are now considered to be exerted
      through nuclear vitamin receptor-mediated gene expression. The vitamin A nuclear
      receptors compromise six members, three all-trans retinoic acid receptors
      (RARalpha, RARbeta, RARgamma) and three 9-cis retinoic acid receptors (RXRalpha,
      RXRbeta, RXRgamma) (Mangelsdorf et al. 1995). Unlike vitamin A receptors, only
      one member is identified for vitamin D. The present study investigating the
      vitamin D receptor function in gene expression in both cell culture and intact
      animals was undertaken to better understand the actions of the fat-soluble
      vitamin A and vitamin D at a molecular level.

PMID- 11242476
TI  - The role of PPARgamma as a thrifty gene both in mice and humans.
AB  - The biological role of peroxisome proliferator-activated receptor gamma
      (PPARgamma) was investigated by gene targeting and case-control study of the
      Pro12Ala PPARgamma2 polymorphism. Homozygous PPARgamma-deficient embryos died at
      10.5-11.5 days post conception (dpc) due to placental dysfunction. Heterozygous
      PPARgamma-deficient mice were protected from the development of insulin
      resistance due to adipocyte hypertrophy under a high-fat diet, whose phenotypes
      were abrogated by PPARgamma agonist treatment. Heterozygous PPARgamma-deficient
      mice showed overexpression and hypersecretion of leptin despite the smaller size
      of adipocytes and decreased fat mass, which may explain these phenotypes at least
      in part. This study reveals a hitherto unpredicted role for PPARgamma in high-fat
      diet-induced obesity due to adipocyte hypertrophy and insulin resistance, which
      requires both alleles of PPARgamma. A Pro12Ala polymorphism has been detected in
      the human PPARgamma2 gene. Since this amino acid substitution may cause a
      reduction in the transcriptional activity of PPARgamma, this polymorphism may be
      associated with decreased insulin resistance and decreased risk of type 2
      diabetes. To investigate this hypothesis, we performed a case-control study of
      the Pro12Ala PPARgamma2 polymorphism. In an obese group, subjects with Ala12 were
      more insulin sensitive than those without. The frequency of Ala12 was
      significantly lower in the diabetic group, suggesting that this polymorphism
      protects against type 2 diabetes. These results revealed that in both mice and
      humans, PPARgamma is a thrifty gene mediating type 2 diabetes.

PMID- 11242477
TI  - Protein nutrition and insulin-like growth factor system.
AB  - Protein metabolism of growing animals is greatly affected by quantity and
      nutritional quality of dietary proteins. When animals are fed diets that contain
      enough proteins of good nutritional quality, they grow well. However, if they are
      fed diets deficient in protein or in some essential amino acids, their growth
      rate is markedly depressed. In this paper, we review the response of plasma
      insulin-like growth factor-I (IGF-I) to quantity and nutritional quality of
      dietary proteins. The sound correlation between plasma IGF-I concentration and
      the gain or loss of body proteins under various nutritional conditions suggests
      that the plasma IGF-I most possibly regulates the growth rate of animals or the
      rate of whole body protein synthesis. The quantity and nutritional quality of
      dietary proteins also regulates plasma concentration of IGF-binding proteins
      (IGFBPs). The changes in plasma concentration of IGFBPs presumably modifies the
      activity of IGF-I to regulate whole body protein synthesis. Molecular mechanisms
      of the changes in plasma concentrations of IGF-I and IGFBPs as affected by
      dietary proteins are also reviewed.

PMID- 11242478
TI  - Regulation of the expression of carbohydrate digestion/absorption-related genes.
AB  - To explore the underlying molecular mechanism whereby nutrients modulate the
      expression of intestinal digestion/absorption-related genes, we have cloned the
      5' flanking regions of two representing disaccharidase genes, i.e. sucrase
      isomaltase (SI) and lactase-phlorizin hydrolase (LPH), and investigated whether
      the binding activity of putative common nuclear factor(s) binding to the cis
      elements located in these regions is altered by dietary manipulations. Oro
      gastric feeding of a sucrose-containing diet to rats caused parallel increases in
      SI mRNA and LPH mRNA levels within 3 h. Among the monosaccharides tested,
      fructose gave rise to the most prominent increase in the mRNA levels of SI and
      LPH genes, which were accompanied by a coordinate rise in the mRNA levels of two
      microvillar hexose transporters, i.e. SGLT1 and GLUT5. Nuclear run-on assays
      revealed that fructose, but not glucose, increased the transcription of SI, LPH
      and GLUT5. DNase I footprinting analysis of the rat LPH gene showed that the
      protected region conserved the same sequence as the cis-element (CE-LPH1)
      reported in the pig LPH gene. Electrophoretic mobility shift assay using CE-LPH1
      and the related cis-element of SI gene (SIF1) revealed that nuclear extracts from
      the jejunum of rats fed the high-starch diet gave greater density of retarded
      bands than those of rats fed the low-starch diet. Force feeding a fructose diet
      gave rise to an increase in the binding of the dimeric nuclear protein (Cdx-2) to
      the SIF1 element. These results suggest that the cis-elements of CE-LPH1 and SIF1
      might be involved in the carbohydrate-induced increases of the transcription of
      LPH and SI, presumably through a change in the expression and/or binding activity
      of Cdx-2.

PMID- 11242479
TI  - Dietary patterns and mortality.

PMID- 11242480
TI  - Divergent changes in serum sterols during a strict uncooked vegan diet in
      patients with rheumatoid arthritis.
AB  - The effects of a strict uncooked vegan diet on serum lipid and sterol
      concentrations were studied in patients with rheumatoid arthritis. The subjects
      were randomized into a vegan diet group (n 16), who consumed a vegan diet for 2-3
      months, or into a control group (n 13), who continued their usual omnivorous
      diets. Serum total and LDL-cholesterol and -phospholipid concentrations were
      significantly decreased by the vegan diet. The levels of serum cholestanol and
      lathosterol also decreased, but serum cholestanol:total cholesterol and
      lathosterol:total cholesterol did not change. The effect of a vegan diet on serum
      plant sterols was divergent as the concentration of campesterol decreased while
      that of sitosterol increased. This effect resulted in a significantly greater
      sitosterol:campesterol value in the vegan diet group than in the control group
      (1.48 (SD 0.39) v. 0.72 (SD 0.14); P < 0.001). A higher concentration of
      campesterol compared with sitosterol is normal in omnivorous subjects and can be
      explained by lower absorption and esterification rates of sitosterol. Our results
      suggest that a strict uncooked vegan diet changes the relative absorption rates
      of these sterols and/or their biliary clearance.

PMID- 11242481
TI  - Acute effect of dietary stanyl ester dose on post-absorptive alpha-tocopherol,
      beta-carotene, retinol and retinyl palmitate concentrations.
AB  - Stanyl esters dissolved in margarine inhibit cholesterol absorption, lower sterol
      absorption in general, and lower serum total cholesterol, LDL-cholesterol and
      plant sterol levels. To find out whether stanyl esters inhibit absorption of fat
      soluble vitamins and beta-carotene in acute experiments, we performed two fat
      tolerance tests fortified with vitamins (retinol 0.9-3.7 mg, alpha-tocopherol 70
      581 mg), beta-carotene (25-150 mg) and squalene (0.5 g) with and without 1 g of
      stanyl ester added to the test meal in ten healthy men. The concentrations or
      areas under the curves (AUC) of cholesterol, triacylglycerols, squalene and alpha
      tocopherol, beta-carotene and retinyl palmitate showed typical postprandial
      changes in serum, chylomicrons, VLDL and VLDL infranatant (intermediate-density
      lipoproteins, LDL and HDL) over 24 h after the test meal without stanyl esters,
      and they were not affected by the addition of stanyl esters. The post-absorptive
      serum campesterol concentration and campesterol : cholesterol were significantly
      lowered at 6-9 h by stanyl ester supplementation, reflecting reduced sterol
      absorption efficiency. Changes in vitamin and beta-carotene AUC did not correlate
      with the given doses. In conclusion, the present study shows that stanyl esters
      dissolved in margarine do not detectably interfere in a short-term study with the
      absorption of alpha-tocopherol, beta-carotene or retinol measured by a 24 h oral
      fat-load test.

PMID- 11242482
TI  - Second meal effect: modified sham feeding does not provoke the release of stored
      triacylglycerol from a previous high-fat meal.
AB  - The present study was carried out to determine whether cephalic stimulation,
      associated with eating a meal, was sufficient stimulus to provoke the release of
      stored triacylglycerol (TAG) from a previous high-fat meal. Ten subjects were
      studied on three separate occasions. Following a 12 h overnight fast, subjects
      were given a standard mixed test meal which contained 56 g fat. Blood samples
      were taken before the meal and for 5 h after the meal when the subjects were
      randomly allocated to receive either water (control) or were modified sham fed a
      low-fat (6 g fat) or moderate-fat (38 g fat) meal. Blood samples were collected
      for a further 3 h. Compared with the control, modified sham feeding a low- or
      moderate-fat meal did not provoke an early entry of TAG, analysed in either
      plasma or TAG-rich lipoprotein (TRL) fraction (density <1.006 kg/l). The TRL
      retinyl ester data showed similar findings. A cephalic phase secretion of
      pancreatic polypeptide, without a significant increase in cholecystokinin levels,
      was observed on modified sham feeding. Although these data indicate that modified
      sham feeding was carried out successfully, analysis of the fat content of the
      expectorant showed that our subjects may have accidentally ingested a small
      amount of fat (0.7 g for the low-fat meal and 2.4 g for the moderate-fat meal).
      Nevertheless, an early TAG peak following modified sham feeding was not
      demonstrated in the present study, suggesting that significant ingestion of food,
      and not just oro-sensory stimulation, is necessary to provoke the release of any
      TAG stored from a previous meal.

PMID- 11242483
TI  - Selenium absorption and retention from a selenite- or selenate-fortified milk
      based formula in men measured by a stable-isotope technique.
AB  - The present study was designed to determine the apparent absorption and retention
      of the inorganic Se compounds SeO3(2-) and SeO4(2-), which are commonly used for
      Se fortification of clinical nutrition products and infant formulas. Ten healthy
      men were fed a milk-based formula labelled with 40 microg Se as 74SeO3(2-) or
      76SeO4(2-) on two consecutive days using a randomised crossover design. Se stable
      isotope analysis of 9 d complete collections of urine and faeces was used to
      calculate apparent Se absorption and retention. Se retention from 74SeO3(2-)
      (41.0 (SD 8.4) %) and from 76SeO4(2-) (46.0 (SD 7.9) %) was not significantly
      different (P > 0.05). However, Se absorption was significantly higher from SeO4(2
      ) than from SeO3(2-) (91.3 (SD 1.4) % v. 50.2 (SD 7.8) %, P < 0.05). Urinary
      excretion of the administered dose was 9.2 (SD 1.8) % for 74SeO3(2-) and 45.3 (SD
      8.2) % for 76SeO4(2-) (P < 0.05). Urinary Se excretion kinetics differed
      significantly for the two Se compounds; 90 % of the total urinary Se was excreted
      after 121 h for 74SeO32- and after 40 h for 76SeO42- These results suggest that
      although Se absorption and urinary excretion differ for SeO3(2-) and SeO4(2-),
      both Se compounds are equally well retained when administered at a relatively low
      dose (40 microg Se). The nutritional impact of Se fortification of foods would
      thus be expected to be similar when SeO4(2-) or SeO3(2-) are used.

PMID- 11242484
TI  - The hypocholesterolaemic effects of sitostanol in the guinea pig are in part
      related to changes in hepatic lipids and lipoprotein composition.
AB  - To evaluate some of the mechanisms involved in the plasma cholesterol lowering of
      sitostanol (SI), male Hartley guinea pigs were fed diets containing cholesterol
      (0.25 g/100 g) and four doses of SI: either 0 (control), 0.75, 1.5 or 2.25 g/100
      g. In addition a negative control (-C) group with dietary cholesterol (0.04 g/100
      g) was included. Corn oil was used as the source of fat and the contribution of
      fat energy was 35 %. Plasma total cholesterol was 43, 49 and 53 % (P < 0.0001)
      lower after SI intake compared to the control. Plasma LDL concentrations were 47,
      53 and 61 % lower with increasing doses of SI. In addition, intake of SI resulted
      in 26-42 % lower hepatic total cholesterol. Hepatic esterified cholesterol and
      triacylglycerols were 32-60 % and 55-61 % lower after SI intake. SI intake
      resulted in favourable plasma and hepatic cholesterol concentrations similar to
      those in guinea pigs fed low levels of dietary cholesterol (-C). The LDL obtained
      from the control group had a higher number of molecules of free and esterified
      cholesterol than the SI groups. SI intake resulted in 69-71 % higher cholesterol
      excretion compared to the control. SI treatment enhanced the total faecal neutral
      sterol excretion by 54-58 % compared to control and by 70-76 % compared to the (
      C) group. These results suggest that SI might have its hypocholesterolaemic
      effect by reducing cholesterol absorption, which results in lower concentration
      of cholesterol in liver. This reduction in hepatic cholesterol might possibly
      alter hepatic cholesterol metabolism and affect lipoprotein concentration and
      composition.

PMID- 11242485
TI  - Blood sulfur-amino acid concentration reflects an impairment of liver
      transsulfuration pathway in patients with acute abdominal inflammatory processes.
AB  - Whole-blood free amino acids were measured in a control group made up of eight
      healthy women fasted for 12 h and also in eight patients with acute pancreatitis,
      five patients with acute cholecystitis and seven patients with acute
      appendicitis. Blood was withdrawn immediately on admission to hospital and again
      3 d later following a controlled peripheral parenteral nutrition diet; this is
      with the exception of the appendicitis group. l-Cystathionine and l-methionine
      concentrations were significantly higher in pancreatitis and appendicitis
      patients when compared with controls. In the pancreatitis and cholecystitis
      patients, l-serine concentration was also significantly higher when compared with
      controls. The l-homocysteine concentration was significantly higher only in the
      appendicitis group when compared with the control group. l-Cystine concentration
      was unchanged in all the patients studied when compared with control subjects.
      The l-methionine : l-cystine ratio was significantly higher and the l-glutamine :
      l-cystine ratio was significantly lower in all the patients when compared with
      controls. The blood S-amino acid pattern reflects an impairment in liver
      transsulfuration pathway during acute abdominal processes. This work supports the
      idea that the l-methionine : l-cystine and l-glutamine : l-cystine ratios can be
      taken as good markers to evaluate the S-amino acid metabolism and suggests the
      importance of using N-acetylcysteine as a required nutrient in these situations.

PMID- 11242486
TI  - Influence of folic acid supplements on the carry-over of folates from the sow to
      the piglet.
AB  - This experiment aimed to investigate the influence of folic acid supplements on
      the carry-over of folates from the sow to the fetus during late gestation and to
      the suckling piglet. Two groups of sixteen German Landrace sows received, during
      gestation and lactation, a diet supplemented with either 0 or 10 mg folic
      acid/kg. Increased folic acid concentrations in the serum of sows were detected
      only at the end of gestation (day 100) and at the end of lactation (day 28). The
      supplementation with folic acid to the sows' diet improved the folic acid supply
      of the fetus compared with unsupplemented controls; values were respectively 92.6
      v. 56.2 nmol folates/l serum in newborn piglets and 171.9 v. 76.3 micromol
      folates/g fresh liver in stillborn piglets (P < 0.05). Folate concentrations in
      colostrum and milk (day 28) were 3.6- and 5.0-times higher in supplemented than
      unsupplemented sows. This treatment effect was also reflected in the serum of
      piglets until weaning. Therefore, the folic acid supply for the suckling piglet
      is dependent mainly upon the carry-over of maternal folates via colostrum and
      milk.

PMID- 11242487
TI  - Effects of maternal iron restriction in the rat on hypoxia-induced gene
      expression and fetal metabolite levels.
AB  - The mechanism by which maternal Fe deficiency in the rat causes fetal growth
      retardation has not been clearly established. This study compared the effects on
      the fetuses from dams fed a control diet with two groups of dams fed Fe
      restricted diets. One Fe-restricted group was fed the Fe-restricted diet for 1
      week prior to mating and throughout gestation and the second Fe-restricted group
      was fed the Fe-restricted diet for 2 weeks prior to mating and throughout
      gestation. On day 21 of gestation Fe-restricted dams, and their fetuses, were
      anaemic. Fetal weight was reduced in both Fe-restricted groups compared with
      controls. Expression of hypoxia-inducible factor (HIF)-1alpha and vascular
      endothelial growth factor (VEGF) are induced by hypoxia. The levels of HIF-1alpha
      mRNA were highest in placenta, then in kidney, heart and liver but were not
      different between the groups. Levels of plasma VEGF were not different between
      the groups. Maternal plasma triacylglycerol was decreased in the 1-week Fe
      restricted dams compared with controls. Maternal plasma cholesterol and free
      fatty acid levels were not different between the groups. In fetal plasma, levels
      of triacylglycerol and cholesterol were decreased in both Fe-restricted groups.
      In maternal plasma, levels of a number of amino acids were elevated in both Fe
      restricted groups. In contrast, levels of a number of amino acids in fetal plasma
      were lower in both Fe-restricted groups. Fetal plasma lactate was increased in Fe
      restricted fetuses but fetal plasma glucose and beta-hydroxybutyrate were not
      affected. These changes in fetal metabolism may contribute to fetal growth
      retardation in this model. This study does not support the hypothesis that the Fe
      restricted fetus is hypoxic.

PMID- 11242488
TI  - Combined effects of red pepper and caffeine consumption on 24 h energy balance in
      subjects given free access to foods.
AB  - The effects of red pepper and caffeine ingestion on energy and macronutrient
      balances were examined in eight Caucasian male subjects. All subjects
      participated in two randomly assigned conditions: control and experimental (red
      pepper and caffeine). After ingesting a standardized breakfast, subjects ate
      three meals ad libitum (lunch, dinner and breakfast) and snacks which were served
      approximately 2 h after the lunch and dinner over a 24 h period. Two appetizers
      with or without 3 g red pepper) were given before lunch and dinner, and a drink
      (decaffeinated coffee with or without 200 mg caffeine) was served at all meals
      and snacks except for the after-dinner snack. It is also important to note that
      on the experimental day, 8.6 and 7.2 g red pepper were also added to lunch and
      dinner respectively. Red pepper and caffeine consumption significantly reduced
      the cumulative ad libitum energy intake and increased energy expenditure. The
      mean difference in energy balance between both conditions was 4000 kJ/d.
      Moreover, the power spectral analysis of heart rate suggested that this effect of
      red pepper was associated with an increase in sympathetic:parasympathetic nervous
      system activity ratio. These results indicate that the consumption of red pepper
      and caffeine can induce a considerable change in energy balance when individuals
      are given free access to foods.

PMID- 11242489
TI  - Quantifying the dietary potassium requirement of juvenile hybrid tilapia
      (Oreochromis niloticus x O. aureus).
AB  - An 8 week feeding trial was conducted to determine the dietary K requirement for
      juvenile hybrid tilapia (Oreochromis niloticus x O. aureus). Purified diets with
      eight levels (0, 1, 2, 3, 4, 5, 7, 10 g/kg diet) of supplemental K were fed to
      tilapia. Each diet was fed to three replicate groups of fish initially weighing a
      mean value of 0.77 (SE 0.01) g/fish in a closed, recirculating rearing system.
      Weight gain was higher (P < 0.05) in fish fed the diets supplemented with 2, 3
      and 4 g K/kg diet than in fish fed diet with 10 g K/kg diet and the
      unsupplemented control diet. Gill Na+-K+ ATPase activity was highest in fish fed
      the diets supplemented with 1-3 g K/kg diet, followed by fish fed the diet with 5
      g K/kg diet and lowest in fish fed the diet with 10 g K/kg diet. Whole-body K
      content in fish were generally increased as the dietary K supplementation level
      increased. Analysis by polynomial regression of weight gain and gill Na+-K+
      ATPase activity and by linear regression of whole-body K retention of the fish
      indicated that the adequate dietary K concentration for tilapia is about 2-3 g/kg
      diet.

PMID- 11242490
TI  - Dietary patterns and mortality in Danish men and women: a prospective
      observational study.
AB  - The analysis of dietary patterns emerged recently as a possible approach to
      examining diet-disease relation. We analysed the risk of all-cause and
      cardiovascular mortality associated with dietary patterns in men and women, while
      taking a number of potential confounding variables into account. Data were from a
      prospective cohort study with follow-up of total and cause-specific mortality. A
      random sample of 3698 men and 3618 women aged 30-70 years and living in
      Copenhagen County, Denmark, were followed from 1982 to 1998 (median 15 years).
      Three dietary patterns were identified from a twenty-eight item food frequency
      questionnaire, collected at baseline: (1) a predefined healthy food index, which
      reflected daily intakes of fruits, vegetables and wholemeal bread, (2) a prudent
      and (3) a Western dietary pattern derived by principal component analysis. The
      prudent pattern was positively associated with frequent intake of wholemeal
      bread, fruits and vegetables, whereas the Western was characterized by frequent
      intakes of meat products, potatoes, white bread, butter and lard. Among
      participants with complete information on all variables, 398 men and 231 women
      died during follow-up. The healthy food index was associated with reduced all
      cause mortality in both men and women, but the relations were attenuated after
      adjustment for smoking, physical activity, educational level, BMI, and alcohol
      intake. The prudent pattern was inversely associated with all-cause and
      cardiovascular mortality after controlling for confounding variables. The Western
      pattern was not significantly associated with mortality. This study partly
      supports the assumption that overall dietary patterns can predict mortality, and
      that the dietary pattern associated with the lowest risk is the one which is in
      accordance with the current recommendations for a prudent diet.

PMID- 11242491
TI  - Serum concentrations of carotenoids and vitamins A, E, and C in control subjects
      from five European countries.
AB  - High intakes of fruits and vegetables, or high circulating levels of their
      biomarkers (carotenoids, vitamins C and E), have been associated with a
      relatively low incidence of cardiovascular disease, cataract and cancer. Exposure
      to a high fruit and vegetable diet increases antioxidant concentrations in blood
      and body tissues, and potentially protects against oxidative damage to cells and
      tissues. This paper describes blood concentrations of carotenoids, tocopherols,
      ascorbic acid and retinol in well-defined groups of healthy, non-smokers, aged 25
      45 years, 175 men and 174 women from five European countries (France, UK
      (Northern Ireland), Republic of Ireland, The Netherlands and Spain). Analysis was
      centralised and performed within 18 months. Within-gender, vitamin C showed no
      significant differences between centres. Females in France, Republic of Ireland
      and Spain had significantly higher plasma vitamin C concentrations than their
      male counterparts. Serum retinol and alpha-tocopherol levels were similar between
      centres, but gamma-tocopherol showed a great variability being the lowest in
      Spain and France, and the highest in The Netherlands. The provitamin A: non
      provitamin A carotenoid ratio was similar among countries, whereas the
      xanthophylls (lutein, zeaxanthin, beta-cryptoxanthin) to carotenes (alpha
      carotene, beta-carotene, lycopene) ratio was double in southern (Spain) compared
      to the northern areas (Northern Ireland and Republic of Ireland). Serum
      concentrations of lutein and zeaxanthin were highest in France and Spain; beta
      cryptoxanthin was highest in Spain and The Netherlands; trans-lycopene tended to
      be highest in Irish males and lowest in Spanish males; alpha-carotene and beta
      carotene were higher in the French volunteers. Due to the study design, the
      concentrations of carotenoids and vitamins A, C and E represent physiological
      ranges achievable by dietary means and may be considered as 'reference values' in
      serum of healthy, non-smoking middle-aged subjects from five European countries.
      The results suggest that lutein (and zeaxanthin), beta-cryptoxanthin, total
      xanthophylls and gamma-tocopherol (and alpha- : gamma-tocopherol) may be
      important markers related to the healthy or protective effects of the
      Mediterranean-like diet.

PMID- 11242492
TI  - Lower BMI cut-off value to define obesity in Hong Kong Chinese: an analysis based
      on body fat assessment by bioelectrical impedance.
AB  - There is increasing evidence suggesting that the cut-off values for defining
      obesity used in the Western countries cannot be readily applied to Asians, who
      often have smaller body frames than Caucasians. We examined the BMI and body fat
      (BF) as measured by bioelectrical impedance in 5153 Hong Kong Chinese subjects.
      We aimed to assess the optimal BMI reflecting obesity as defined by abnormal BF
      in Hong Kong Chinese. Receiver operating characteristic curve (ROC) analysis was
      used to assess the optimal BMI predicting BF at different levels. The mean age
      and SD of the 5153 subjects (3734 women and 1419 men) was 51.5 (SD 16.3) years
      (range: 18.0-89.5 years, median: 50.7 years). Age-adjusted partial correlation
      (r) between BMI and BF in women and men were 0.899 (P < 0.001) and 0.818 (P <
      0.001) respectively. Using ROC analysis, the BMI corresponding to the
      conventional upper limit of normal BF was 22.5-23.1 kg/m(2), and the BMI
      corresponding to the 90 percentiles of BF was 25.4-26.1 kg/m(2). Despite similar
      body fat contents, the BMI cut-off value used to define obesity in Hong Kong
      Chinese should be lower as compared to Caucasians. We suggest a BMI of 23 kg/m(2)
      and 26 kg/m(2) as the cut-off values to define overweight and obesity
      respectively in Hong Kong Chinese.

PMID- 11242493
TI  - Parathyroid hormone and dietary calcium.

PMID- 11242494
TI  - Drugs for hypertension.

PMID- 11242495
TI  - The cost-utility of screening for depression in primary care.
AB  - BACKGROUND: Depressive disorders are common in primary care and cause substantial
      disability, but they often remain undiagnosed. Screening is a frequently proposed
      strategy for increasing detection of depression. OBJECTIVE: To examine the cost
      utility of screening for depression compared with no screening. DESIGN:
      Nonstationary Markov model. DATA SOURCES: The published literature. TARGET
      POPULATION: Hypothetical cohort of 40-year-old primary care patients. TIME
      HORIZON: Lifetime. PERSPECTIVE: Health care payer and societal. INTERVENTIONS:
      Self-administered questionnaire followed by provider assessment. OUTCOME
      MEASURES: Costs and quality-adjusted life-years (QALYs). RESULTS OF BASE-CASE
      ANALYSIS: Compared with no screening, the cost to society of annual screening for
      depression in primary care patients is $192 444/QALY. Screening every 5 years and
      one-time screening cost $50 988/QALY and $32 053/QALY, respectively, compared
      with no screening. From the payer perspective, the cost of annual screening is
      $225 467. RESULTS OF SENSITIVITY ANALYSES: Cost-utility ratios are most sensitive
      to the prevalence of major depression, the costs of screening, rates of treatment
      initiation, and remission rates with treatment. In Monte Carlo sensitivity
      analyses, the cost-utility of annual screening is less than $50 000/QALY only
      2.2% of the time. In multiway analyses, four model variables must be changed to
      extreme values for the cost-utility of annual screening to fall below $50
      000/QALY, but a change in only one variable increases the cost-utility of one
      time screening to more than $50 000/QALY. One-time screening is more robustly
      cost-effective if screening costs are low and effective treatments are being
      given. CONCLUSIONS: Annual and periodic screening for depression cost more than
      $50 000/QALY, but one-time screening is cost-effective. The cost-effectiveness of
      screening is likely to improve if treatment becomes more effective.

PMID- 11242496
TI  - Therapy for Helicobacter pylori in patients with nonulcer dyspepsia. A meta
      analysis of randomized, controlled trials.
AB  - PURPOSE: To assess the effect of eradication therapy for Helicobacter pylori on
      symptoms of nonulcer dyspepsia. DATA SOURCES: Duplicate searches of bibliographic
      databases, reviews of proceedings of annual gastroenterology and H. pylori
      meetings from 1995 to 1999, reviews of reference lists, and contact with primary
      investigators and pharmaceutical manufacturers. STUDY SELECTION: Included studies
      1) examined patients with nonulcer dyspepsia and H. pylori infection; 2) used
      combination therapy for H. pylori and a control therapy without efficacy against
      H. pylori; 3) were randomized, controlled trials; 4) lasted for at least 1 month
      after the end of therapy; and 5) assessed symptoms of nonulcer dyspepsia. Ten
      studies were included. DATA EXTRACTION: Independent, duplicate data extraction of
      the methodologic quality, population, intervention, study design, duration, and
      outcome of the trials. DATA SYNTHESIS: The odds ratio (OR) for treatment success
      in nonulcer dyspepsia with H. pylori eradication therapy compared with control
      therapy was 1.29 (95% CI, 0.89 to 1.89; P = 0.18). However, significant
      heterogeneity (P = 0.04) calls the validity of aggregating the data into
      question. Heterogeneity resolved with the exclusion of one study (OR, 1.07 [CI,
      0.83 to 1.37]; P > 0.2). For predefined analysis of trials that used a
      specifically stated definition of dyspepsia (that is, upper abdominal pain or
      discomfort), the OR was 1.04 (CI, 0.80 to 1.35) without heterogeneity. For
      treatment that resulted in cure rather than persistent infection, the OR was 1.17
      (CI, 0.87 to 1.59) without heterogeneity. CONCLUSION: This meta-analysis provides
      little support for the use of H. pylori eradication therapy in patients with
      nonulcer dyspepsia.

PMID- 11242497
TI  - Should all patients with type 1 diabetes mellitus and microalbuminuria receive
      angiotensin-converting enzyme inhibitors? A meta-analysis of individual patient
      data.
AB  - PURPOSE: To determine whether response of albumin excretion rate to angiotensin
      converting enzyme (ACE) inhibitors has a threshold in patients with type 1
      diabetes mellitus and microalbuminuria and to examine treatment effect according
      to covariates. DATA SOURCES: Studies were identified by searching MEDLINE and
      related bibliographies. STUDY SELECTION: Selected studies included at least 10
      normotensive patients with type 1 diabetes mellitus and microalbuminuria, had a
      placebo or nonintervention group, and included at least 1 year of follow-up. DATA
      EXTRACTION: Raw data were obtained for 698 patients from the 12 identified
      trials. Analysis of treatment effect at 2 years was restricted to trials with at
      least 2 years of follow-up (646 patients from 10 trials). DATA SYNTHESIS: In
      patients receiving ACE inhibitors, progression to macroalbuminuria was reduced
      (odds ratio, 0.38 [95% CI, 0.25 to 0.57]) and the odds ratio for regression to
      normoalbuminuria was 3.07 (CI, 2.15 to 4.44). At 2 years, albumin excretion rate
      was 50.5% (CI, 29.2% to 65.5%) lower in treated patients than in those receiving
      placebo (P < 0.001). Estimated treatment effect varied by baseline albumin
      excretion rate (74.1% and 17.8% in patients with a rate of 200 microg/min and 20
      microg/min, respectively [P = 0.04]) but not by patient subgroup. Adjustment for
      change in blood pressure attenuated the treatment difference in albumin excretion
      rate at 2 years to 45.1% (CI, 18.6% to 63.1%; P < 0.001). CONCLUSIONS: In
      normotensive patients with type 1 diabetes mellitus and microalbuminuria, ACE
      inhibitors significantly reduced progression to macroalbuminuria and increased
      chances of regression. Beneficial effects were weaker at the lowest levels of
      microalbuminuria but did not differ according to other baseline risk factors.
      Changes in blood pressure cannot entirely explain the antiproteinuric effect of
      ACE inhibitors.

PMID- 11242499
TI  - Update in addiction medicine.

PMID- 11242498
TI  - Improvement in atrophic gastritis and intestinal metaplasia in patients in whom
      Helicobacter pylori was eradicated.
AB  - BACKGROUND: Glandular atrophy and intestinal metaplasia are precancerous lesions;
      whether Helicobacter pylori eradication affects these lesions is controversial.
      OBJECTIVE: To determine whether H. pylori eradication is associated with
      improvement in glandular atrophy and intestinal metaplasia after at least 1 year.
      DESIGN: Single-blind, uncontrolled prospective trial. SETTING: Academic
      gastroenterology clinic in Japan. PATIENTS: 163 consecutive patients with
      dyspepsia and H. pylori infection. INTERVENTION: One-week course of a proton-pump
      inhibitor and antibiotic therapy. MEASUREMENTS: Endoscopic examination with
      antral and corporal biopsy was done before treatment and at 1 to 3 and 12 to 15
      months after treatment. Gastritis, atrophy, and metaplasia were graded according
      to the updated Sydney System. RESULTS: In the 115 patients in whom H. pylori was
      eradicated, inflammation and mean neutrophil activity had decreased by 1 to 3
      months, and both glandular atrophy in the corpus and intestinal metaplasia in the
      antrum had decreased by 12 to 15 months. Glandular atrophy in the corpus improved
      in 34 (89%) of 38 patients with atrophy before treatment, and intestinal
      metaplasia in the antrum improved in 28 (61%) of 46 patients who had metaplasia
      at baseline. In the 48 patients in whom eradication was unsuccessful, no
      significant histologic changes were observed. CONCLUSION: In the year after
      successful H. pylori eradication, precancerous lesions improved in most patients.

PMID- 11242500
TI  - Sleep and sleep disorders in pregnancy.
AB  - Sleep problems are common in pregnant women. This review examines sleep in normal
      pregnancy; discusses the physiologic bases for alterations in sleep, including
      hormonal and mechanical factors; and correlates these factors with changes in
      sleep of pregnant women, as determined subjectively by surveys and objectively by
      polysomnographic studies. The changes in respiratory physiology during pregnancy,
      the possible predisposition of the pregnant woman to sleep-disordered breathing
      because of these changes, and results of published studies of sleep-disordered
      breathing in pregnancy are discussed. Finally, the effect of pregnancy on other
      sleep disorders and the management of these sleep disorders during pregnancy are
      outlined, including changes in management necessitated by this state. The paucity
      of available data and the need for further studies of incidence and outcomes of
      sleep disorders in the pregnant woman are emphasized.

PMID- 11242501
TI  - Clinical trials that have influenced the treatment of venous thromboembolism: a
      historical perspective.
AB  - In 1960, Barritt and Jordan performed the first randomized trial demonstrating
      the efficacy of anticoagulant therapy in the treatment of venous thromboembolism.
      Since then, important therapeutic advances have been made in the treatment of
      deep venous thrombosis and pulmonary embolism. This paper reviews the important
      clinical trials involving anticoagulant therapy and vena caval interruption. The
      studies are discussed from a historical perspective, and an attempt is made to
      analyze both the thought processes that prompted their design and the reasons why
      they changed practice.

PMID- 11242502
TI  - Depression screening is not enough.

PMID- 11242503
TI  - Antipersonnel land mines: a vector for human suffering.

PMID- 11242504
TI  - Tragic events of April 1996.

PMID- 11242505
TI  - Tragic events of April 1996.

PMID- 11242506
TI  - Tragic events of April 1996.

PMID- 11242507
TI  - Tragic events of April 1996.

PMID- 11242508
TI  - Tragic events of April 1996.

PMID- 11242510
TI  - Losartan reduces hematocrit in patients with chronic obstructive pulmonary
      disease and secondary erythrocytosis.

PMID- 11242511
TI  - Possible drug interaction between itraconazole and vinorelbine tartrate leading
      to death after one dose of chemotherapy.

PMID- 11242512
TI  - James Edgar Paullin: internist to Franklin Delano Roosevelt, oslerian, and
      forgotten leader of American medicine.

PMID- 11242515
TI  - Clinical and immunological benefits from highly active antiretroviral therapy in
      spite of limited viral load reduction in HIV type 1 infection.
AB  - Both naive and memory T lymphocyte responses are lost during advanced HIV
      infection. Treatment with highly active antiretroviral therapy (HAART) is
      associated with an increase in T lymphocytes and a reduction in viral load.
      However, the viral response to HAART in patients with low levels of helper T
      lymphocytes and a high viral load is often not satisfactory. We investigated the
      capacity of long-term HAART to reconstitute the immune system in severely ill
      patients. A nonselected longitudinal patient population with high baseline viral
      levels and CD4(+) cells below 100 x 10(6)/liter were monitored for 2 years during
      HAART. Markers to estimate the therapeutic effects included viral levels and cell
      surface markers representing naive and memory T lymphocytes as well as activation
      markers, B cells, NK cells, and clinical events. After 2 years of treatment,
      viral load was reduced to undetectable levels in 55% (viral responders, vRs) and
      less than 1 log (median value) from baseline in 45% (viral low responders, vLRs).
      Elevated numbers of memory and naive CD4(+) and CD8(+) cells as well as a
      decrease in activation markers were seen in both vRs and vLRs. However, the
      magnitude was greater in vRs. No differences in the clinical outcome were
      observed between vRs and vLRs. We conclude that most patients, even in advanced
      stages of HIV disease, benefited from HAART. The magnitude of the response was
      related to good viral reduction, but even patients with poor viral reduction had
      a recovery of naive and memory CD4(+) and CD8(+) cells. Even a small reduction in
      viral load is thus of importance for health and potentially also for years of
      survival.

PMID- 11242516
TI  - High levels of CD8-positive lymphocytes expressing CD45R0, granzyme B, and Ki-67
      in lymph nodes of HIV-infected individuals are not associated with increased
      mortality.
AB  - Lymph nodes constitute the major site of HIV replication and of immunological
      response to HIV. To study the role of cytotoxic and mitotic active CD8(+)
      lymphocytes in lymph nodes during HIV infection we examined 28 formalin-fixed,
      paraffin-embedded lymph nodes sampled from 1984 to 1986 from 21 HIV-seropositive
      patients and seven HIV-negative patients. Eleven of the HIV-positive patients
      died within 78 months of biopsy time and 10 patients were alive on July 1, 1998.
      Double immunohistochemical staining procedures were developed to identify CD8(+)
      cells expressing CD45R0, granzyme B, and Ki-67. A stereological method was used
      to count the different cell types in the lymph nodes. There were no significant
      differences in the total cell (nucleated) and CD3(+) cell concentrations between
      the three groups. However, there were significantly higher concentrations of
      CD3(+)CD8(+), CD8(+)CD45R0(+), and CD8(+)Ki-67(+) lymphocytes in the HIV patients
      compared with the control group. Furthermore, there was a tendency for the HIV
      deceased group to have lower levels of CD8(+)granzyme B(+) and CD8(+)Ki-67(+)
      lymphocyte concentrations compared with the HIV-alive group. Three HIV patients,
      who progressed to death within 49 months of biopsy time, were among the patients
      with the lowest concentrations of CD8(+)granzyme B(+) and CD8(+)Ki-67(+)
      lymphocytes. This finding allowed us to conclude that CD8(+) lymphocytes
      expressing high levels of CD45R0, granzyme B, and Ki-67 in lymph nodes of HIV
      patients are not related to increased mortality, whereas low concentrations of
      CD8(+) granzyme B(+) and CD8(+)Ki-67(+) lymphocytes may be associated with poor
      prognosis.

PMID- 11242517
TI  - Inhibition of HIV type 1 replication by simultaneous infection of peripheral
      blood lymphocytes with human immunodeficiency virus types 1 and 2.
AB  - A productive infection of peripheral blood lymphocytes by HIV-1 was severely
      inhibited by the simultaneous infection of these cells with HIV-2. A similar
      reciprocal effect on HIV-2 infection was not observed. The extent of virus
      replication was determined by virus-specific antigen capture assays of the
      supernatants of the infections. The inhibitory effect was observed with T cell
      tropic, dual-tropic, as well as with primary HIV-1 isolates from different
      subtypes (A, B, C, E, F, and O). Infection of PBLs with different subtypes of HIV
      2 (A and B) as well as with SIV(mac) resulted in the inhibition of HIV-1.
      However, the inhibitory effect was limited to PBLs; similar results were not
      observed in a T cell line. The inhibition of HIV-1 replication was independent of
      HIV-2 concentration; however, the infection by HIV-2 had to take place within 24
      hr after PBLs were infected by HIV-1 for inhibition of HIV-1 replication to
      occur. The inhibition could be reversed by the addition of PHA. Analysis of HIV-1
      RNA and DNA demonstrated that the inhibition was not at uptake or reverse
      transcription and that equal amounts of PBLs were infected by HIV-1 in single
      infections and coinfections. Immunocytochemical analysis of HIV-1 proteins
      demonstrated that equal numbers of cells were infected and that equal amounts of
      intracellular HIV-1 Env and Gag proteins were produced throughout the culture
      period. Therefore we conclude that HIV-2 can potently inhibit the productive
      infection of PBLs by HIV-1 and that the mechanism of this inhibition appears to
      prevent HIV-1 assembly or release from PBLs.

PMID- 11242518
TI  - Membrane-perturbing domains of HIV type 1 glycoprotein 41.
AB  - Structural and functional studies were performed to assess the membrane actions
      of peptides based on HIV-1 glycoprotein 41,000 (gp41). Previous site-directed
      mutagenesis of gp41 has shown that amino acid changes in either the N-terminal
      fusion or N-leucine zipper region depressed viral infection and syncytium
      formation, while modifications in the C-leucine zipper domain both increased and
      decreased HIV fusion. Here, synthetic peptides were prepared corresponding to the
      N-terminal fusion region (FP-I; gp41 residues 519-541), the nearby N-leucine
      zipper domain (DP-107; gp41 residues 560-597), and the C-leucine zipper domain
      (DP-178; gp41 residues 645-680). With erythrocytes, FP-I or DP-107 induced dose
      dependent hemolysis and promoted cell aggregation; FP-I was more hemolytic than
      DP-107, but each was equally effective in aggregating cells. DP-178 produced
      neither hemolysis nor aggregation, but blocked either FP-I- or DP-107-induced
      hemolysis and aggregation. Combined with previous nuclear magnetic resonance and
      Fourier transform infrared spectroscopic results, circular dichroism (CD)
      spectroscopy showed that the alpha-helicity for these peptides in solution
      decreased in the order: DP-107 >> DP-178 > FP-I. CD analysis also indicated
      binding of DP-178 to either DP-107 or FP-I. Consequently, DP-178 may inhibit the
      membrane actions mediated by either FP-I or DP-107 through direct peptide
      interactions in solution. These peptide results suggest that the corresponding N
      terminal fusion and N-leucine zipper regions participate in HIV infection, by
      promoting membrane perturbations underlying the merging of the viral envelope
      with the cell surface. Further, the C-leucine zipper domain in "prefusion" HIV
      may inhibit these membrane activities by interacting with the N-terminal fusion
      and N-leucine zipper domains in unactivated gp41. Last, exogenous DP-178 may bind
      to the N-terminal and N-leucine zipper domains of gp41 that become exposed on HIV
      stimulation, thereby preventing the fusogenic actions of these gp41 regions
      leading to infection.

PMID- 11242519
TI  - Increased soluble Fas in HIV-infected hemophilia patients with CD4+ and CD8+ cell
      count increases and viral load and immune complex decreases.
AB  - Previous studies interpreted increases of soluble Fas (sFas) in the plasma during
      disease progression in HIV-infected patients as evidence of increased apoptosis
      of CD4(+) lymphocytes. We studied whether sFas and sFas ligand (sFasL) plasma
      levels are associated with CD4(+) and CD8(+) lymphocyte counts, plasma viral
      load, and IgM, IgG, C3d, and gp120 complexes on circulating CD4(+) blood
      lymphocytes in long-term surviving HIV-infected hemophilia patients, most of whom
      were receiving HAART. Twenty-six hemophilia patients who were infected with HIV
      in the early 1980s were investigated in 1997, 1998, and 1999. HAART was initiated
      in 1996 and 1997 in most patients. Lymphocyte subpopulations and immune complex
      coated CD4(+) lymphocytes in the blood were investigated by flow cytometry,
      plasma viral load (HIV-1 mRNA copies/ml plasma) was tested with HIV-1 QT
      Nuclisens kits, sFas (ng/ml) and sFasL (ng/ml) plasma levels were measured with
      MBL ELISA kits, and the in vitro response of patient lymphocytes was tested in
      cell cultures. During the period from 1997 to 1999 we observed an increase in
      sFas plasma levels (p = 0.003) as well as in CD4(+) (p = 0.004) and CD8(+) (p =
      0.023) cell counts; a decrease in IgG (p = 0.047), C3d (p = 0.024), and gp120 (p
      = 0.001)-coated CD4(+) lymphocytes in the blood; and a decrease in the number of
      impaired mitogen stimulation assays (p = 0.013). sFas was negatively associated
      with viral burden (r = -0.662, p = 0.0002) as well as with CD4(+)IgM(+) (r = 
      0.554, p = 0.004), CD4(+)IgG(+) (r = -0.431, p = 0.031), CD4(+)C3d(+) (r = 
      0.551, p = 0.041), and CD4(+)gp120(+) (r = -0.430, p = 0.041) blood lymphocytes,
      CD8(+)DR(+) cell counts (r = -0.700, p = 0.016), and impaired in vitro responses
      of patient lymphocytes to PHA (r = -0.475, p = 0.016). sFasL was negatively
      associated with total lymphocyte counts (r = -0.433, p = 0.027), as well as with
      absolute numbers of CD3(+) (r = -0.492, p = 0.011) and CD8(+) (r = -0.432, p =
      0.027) cells. We conclude that, contrary to expectations, sFas plasma levels
      increased in long-term surviving HIV-infected hemophilia patients receiving
      HAART, concomitant with increases in CD4(+) and CD8(+) cell counts. Increased
      sFas may reflect the growing pool of T lymphocytes that recovers because of a
      decreasing viral burden and a decreasing immune complex load of CD4(+)
      lymphocytes.

PMID- 11242520
TI  - Sequence variations in the amino- and carboxy-terminal parts of the surface
      envelope glycoprotein of HTLV type 1 induce specific neutralizing antibodies.
AB  - The surface envelope glycoprotein gp46 of the human T cell leukemia virus type 1
      elicits a strong immune response. Its protective role against HTLV-1 infection in
      animal models is well established, suggesting that recombinant envelope
      glycoproteins or synthetic peptides could be used as an effective vaccine.
      However, reports have indicated that some variations in envelope sequences may
      induce incomplete cross-neutralization between HTLV-1 strains. To identify amino
      acid changes that might be involved in induction of specific neutralizing
      antibodies, we studied sera from three patients (2085, 2555, and 2709) infected
      by HTLV-1 with surface glycoprotein gp46 harboring variations in amino acid
      sequence at positions 39, 72, 265, and 290. Inhibition of syncytia induced by
      parental, chimeric, or point-mutated envelope proteins indicated that sera 2555
      and 2709 primarily recognized neutralizable epitopes located in N- and C-terminal
      parts of the gp46 glycoprotein. Amino acids changes at positions 39, 265, and 290
      greatly impaired recognition of neutralizing epitopes recognized by these two
      sera. These results demonstrate that amino acid changes in envelope glycoprotein
      gp46 can induce strain-specific neutralizing antibodies in some patients. On the
      other hand, the neutralizing activity of serum 2085 was not affected by amino
      acid changes at positions 39, 265, and 290, suggesting that the neutralizing
      antibodies present in this serum were directed against epitopes located in other
      parts of the molecule, possibly those located in the central domain of the
      molecule, which has the same amino acid sequence in the three viruses.

PMID- 11242521
TI  - Detection of viral RNA in CD4(-)CD8(-) and CD4(-)CD8(+) lymphocytes in vivo in
      rhesus monkeys infected with simian immunodeficiency virus of macaques.
AB  - A definition of the specific cell types that support HIV replication early in the
      course of infection will be important for understanding AIDS pathogenesis and
      designing strategies for preventing infection. Observations have indicated that
      the population of lymphocytes susceptible to productive infection extends beyond
      activated CD4(+) T cells. To explore this issue, we have employed laser scanning
      cytometry technology and the techniques of lymphocyte surface immunophenotyping
      followed by fluorescent in situ hybridization to detect simian immunodeficiency
      virus of macaques (SIVmac) RNA in phenotypically defined rhesus monkey
      lymphocytes. The immunophenotype of productively infected cells in either a
      rhesus monkey T cell line or in PBMCs infected in vitro with SIVmac was
      remarkably similar to that observed in productively infected PBMCs obtained from
      monkeys during primary infection. We observed low levels or no detectable
      expression of CD4 on cells infected in vitro or on PBMCs of infected monkeys.
      However, a substantial number of SIVmac-infected PBMCs both in cultured
      lymphocytes and sampled directly from infected monkeys expressed CD8 but not CD4.
      These observations are consistent with the possibility that the CD4 molecule may
      be modulated off the surface of CD4(+)CD8(-) or CD4(+)CD8(+) lymphocytes after
      infection or that infection occurred via a CD4-independent mechanism. Moreover,
      there was no preferential expression of CD25 on cells positive for SIVmac RNA,
      which might have been predicted if replication of the virus was occurring
      selectively in activated lymphocytes. These results broaden the range of
      lymphocytes that support productive SIVmac infection to include CD4(-)CD8(-) and
      CD4(-)CD8(+) subsets, and are consistent with virus replication occurring in
      nonactivated cells.

PMID- 11242522
TI  - Predominance of HIV type 1 subtype G among commercial sex workers from Kinshasa,
      Democratic Republic of Congo.
AB  - We have investigated the genetic diversity and potential mosaic genomes of HIV-1
      during the early part of the HIV-1 epidemic among commercial sex workers (CSWs)
      in Kinshasa, Democratic Republic of Congo (formerly Zaire). Serologic analysis
      revealed that 27 (28.7%) of the 94 specimens were seropositive by both peptide
      and whole-virus lysate EIAs and that 24 were positive by molecular screening
      assays, using generic primers that can detect all known groups of HIV-1.
      Phylogenetic analyses of the gag(p24), C2V3, and gp41 regions of these 24
      specimens showed that all were group M; none of them had any evidence of group O,
      N, or SIVcpz-like sequences. On the basis of env sequence analysis, the 24 group
      M specimens were classified as subtypes G (37.5%), A (21%), F1 (12.5%), CRF01_AE
      (8%), D (4%), and H (4%); 3 (12.5%) were unclassifiable (U). Similar analysis of
      the gag(p24) region revealed that the majority of infections were subtype A;
      however, one-third of the specimens were subtype G. Parallel analysis of gag(p24)
      and env regions revealed discordant subtypes in many specimens that may reflect
      possible dual and/or recombinant viruses. These data suggest a predominance of
      subtype G (both pure G and recombinant CRF02_AG) during the early part of the
      epidemic in Kinshasa. Infections with group N or SIVcpz-like viruses were not
      present among these CSWs in Kinshasa.

PMID- 11242523
TI  - Isolation and phylogeny of new endogenous retroviral sequences belonging to the
      HERV-F family.
AB  - A new human endogenous retroviral family (HERV-F) has been identified from human
      chromosome 7q31.1-q31.3 that was identical to the XA34 cDNA clone isolated from a
      human glioma cDNA library with an ERV-9 env probe. We investigated pol gene
      sequences of the HERV-F family from a human monochromosomal DNA panel and
      analyzed these with HERV-F. The pol gene sequences of the HERV-F family were
      detected on chromosomes 3, 6, 7, 10, 11, 14, 19, 20, X, and Y as examined by PCR.
      Thirty-six pol gene sequences identified from the human chromosomes have a high
      degree of sequence similarity (80-99%) with that of the HERV-F. Phylogenetic
      analysis of pol gene sequences distinctively showed four groups, indicating that
      the HERV-F family could be amplified at least four times after the original
      integration into the human genome or represent integration events separately
      during hominid evolution. One clone (HFY-3) on chromosome Y shared 100% sequence
      identity with a clone (HF19-2) on chromosome 19, and a clone (HF20-6) on
      chromosome 20 suggests either a recent retrotransposition or a chromosomal
      translocation. The history of endogenous retroviral sequences may contribute to
      an understanding of evolutionary change in human genomes.

PMID- 11242524
TI  - Cloning and sequencing of cynomolgus macaque CCR3, GPR15, and STRL33: potential
      coreceptors for HIV type 1, HIV type 2, and SIV.
AB  - The characterization of several seven-transmembrane G protein-coupled receptors,
      which function as coreceptors for HIV-1, HIV-2, and/or SIV, has opened up a whole
      new area of AIDS research. Animal models that have played a central role in the
      understanding of lentivirus pathogenesis and the design of novel vaccine
      strategies may also be invaluable in studying the role of these secondary
      receptors in infection and disease progression. However, since it is known that
      minor species-specific sequence changes in CCR3 and STRL33 affect their ability
      to act as coreceptors for HIV-1, HIV-2, and/or SIV, it is important to ascertain
      whether the relevant receptors function as expected in the animal model of
      choice. Many studies have been performed on the function of rhesus macaque
      receptors, but not on the cynomolgus macaque equivalents. Both species are used
      as animal models for lentivirus pathogenesis, but since there are differences in
      their susceptibility to viral infection, we felt it was important for information
      to be available for both rhesus and cynomolgus macaque receptors. The sequence of
      three cynomolgus macaque receptors, CCR3, GPR15, and STRL33, are presented in
      this sequence note. These sequences are compared with already published human and
      rhesus macaque homologs. Functional studies are currently being performed on
      these three cynomolgus macaque receptors to determine their ability to function
      as coreceptors for HIV-2, SIV, and/or SHIV isolates.

PMID- 11242526
TI  - Enhanced efficiency by centrifugal manipulation of adenovirus-mediated
      interleukin 12 gene transduction into human monocyte-derived dendritic cells.
AB  - Transduction of dendritic cells (DCs) with genes encoding tumor-associated
      antigen or with other genes that enhance immune reaction has been theorized to be
      potentially useful for enhancing the efficiency of DC-based immunotherapy.
      However, gene transduction of DCs generated from human peripheral blood monocytes
      has been of limited use because of the low efficiency. Here, we report that the
      efficiency of in vitro adenovirus-mediated gene transduction into human monocyte
      derived DCs can be dramatically enhanced by centrifugation. The best conditions
      for centrifugal gene transduction were determined to be as follows: 2000 x g at
      37 degrees C for 2 hr at a multiplicity of infection (MOI) of 10 or greater. By
      this centrifugal method, approximately 88 and 70% of DCs were gene transducible
      at an MOI of 50 and 10, respectively. Functional analysis showed that DCs
      transduced with human interleukin 12 (IL-12)-expressing adenoviral vector under
      the optimal conditions of centrifugation stably produced IL-12 protein at high
      levels (8.1 ng/10(6) cells/48 hr). IL-12 gene-modified DCs (DC/IL-12) displayed a
      more mature phenotype than nontransduced DCs, as judged by decreased expression
      of CD1a and increased expression of CD83, B7.1 (CD80), B7.2 (CD86), and MHC class
      I and II molecules. DC/IL-12 showed a high phagocytic ability similar to
      nontransduced DCs and were significantly superior to control DCs in the
      stimulation of autologous and allogeneic T lymphocyte responses. The centrifugal
      transduction method with adenoviral vector might be useful for efficient
      generation of gene-modified DCs because it is very simple, highly efficient,
      reproducible, and not cytopathic. IL-12 gene-modified human DCs may be
      therapeutically useful as a good adjuvant in DC-based immunotherapy.

PMID- 11242525
TI  - Receptor-specific targeting mediated by the coexpression of a targeted murine
      leukemia virus envelope protein and a binding-defective influenza hemagglutinin
      protein.
AB  - The entry of retroviral vectors into cells requires two events: binding to a cell
      surface receptor and the subsequent fusion of viral and cellular membranes. The
      host range of a vector is therefore determined largely by the receptor
      specificity of the fusion protein contained in the outer viral envelope. Previous
      attempts to generate targeted retroviral vectors have included the addition of
      targeting ligands to the murine leukemia virus envelope protein (MuLV Env).
      Although such proteins frequently display modified cell-binding characteristics,
      the interaction with the targeted receptors fails to trigger virus-cell fusion.
      Here, we report the use of a binding-defective but fusion-competent hemagglutinin
      (HA) protein to complement the fusion defect in a chimeric MuLV Env targeted to
      the Flt-3 receptor. Retroviral vectors containing both proteins showed enhanced
      transduction of cells expressing Flt-3, which was abrogated by preincubating the
      target cells with soluble Flt-3 ligand. Furthermore, the fusion function of HA
      was absolutely required. These data demonstrate that it is possible to separate
      the binding and fusion events of retroviral entry, using two separate proteins,
      and suggest that varying the binding protein component in this scheme may allow a
      general strategy for targeting retroviral vectors.

PMID- 11242527
TI  - Adenovirus-mediated human endostatin gene delivery demonstrates strain-specific
      antitumor activity and acute dose-dependent toxicity in mice.
AB  - Purified recombinant mouse endostatin protein has been reported to regress
      established murine solid tumors by inhibiting the proliferation of endothelial
      cells. To develop a clinical gene therapy strategy with endostatin, we cloned the
      cDNA of human endostatin by RT-PCR from human placenta. A 150-bp sequence
      encoding the IgG leader peptide was fused in frame to the 5' end of the
      endostatin cDNA and recombinant adenoviruses, AdENDO-YFP and AdENDO, carrying
      endostatin gene expression cassettes were rescued. AdENDO-YFP infects cultured
      mammalian cells at high efficiency and expresses a biologically active human
      endostatin in secreted form at high levels both in vitro and in vivo. When
      delivered in vivo, a strain-specific expression pattern was observed, with the
      highest and longest endostatin expression in 129/J mice. After systemic delivery
      of 2 x 10(9) PFU of AdENDO-YFP into 129/J mice, human endostatin expression was
      achieved at a mean value of 1.34 +/- 0.42 microg/ml of serum (n = 6) and
      inhibition of lung metastasis was observed in an EOMA tumor model. However, high
      dose intravenous delivery of AdENDO-YFP and AdENDO was associated with severe
      acute toxicity in recipient mice that included loss of weight, bleeding, and
      death of animals. These events were not observed with the injection of identical
      doses of a control adenovirus that did not contain the endostatin gene. Because
      the endostatin adenovirus-associated acute toxicity was also observed in
      immunodeficient NCRNU-M nude mice, the toxicity does not appear to be the result
      of the immunogenicity against human endostatin or the EYFP protein.

PMID- 11242528
TI  - Lack of superinfection interference in retroviral vector producer cells.
AB  - Vesicular stomatitis virus G protein (VSV-G)-pseudotyped retroviral vectors have
      become more feasible for clinical gene transfer protocols since stable
      tetracycline (tet)-regulated packaging cell lines have become available. Here, we
      analyzed superinfection interference in VSV-G-pseudotyped and classic amphotropic
      packaging cell lines. No superinfection interference was observed in VSV-G
      pseudotyped packaging cell lines. Thus, integrated retroviral vector genomes
      accumulated during culture. Similar results were obtained with the amphotropic
      packaging cells, but to a lesser degree. In addition, VSV-G packaging cells were
      susceptible to infection with vector particles devoid of envelope proteins, which
      are produced by these cells in high titers when VSV-G expression is suppressed by
      tetracycline. For both packaging systems, superinfection could be blocked by
      azidothymidine (AZT). With regard to safety, this study suggests that in clinical
      protocols amphotropic producer clones should be tested for superinfection
      interference and VSV-G packaging cells should always be cultured in the presence
      of AZT.

PMID- 11242529
TI  - Partial prevention of cisplatin-induced neuropathy by electroporation-mediated
      nonviral gene transfer.
AB  - Cisplatin-induced sensory peripheral neuropathy is the dose-limiting factor for
      cisplatin chemotherapy. We describe the preventive effect of NT-3 delivery, using
      direct gene transfer into muscle by in vivo electroporation in a mouse model of
      cisplatin-induced neuropathy. Cisplatin-induced neuropathy was produced by weekly
      injections of cisplatin (five injections). Two doses of plasmid DNA encoding
      murine NT-3 (pCMVNT-3) were tested (5 and 50 microg/animal/injection). Cisplatin
      treated mice were given two intramuscular injections. The first injection of
      pCMVNT-3 was given 2 days before the first injection of cisplatin and the second
      injection 2 weeks later. Six weeks after the start of the experiment, measurement
      of NT-3 levels (ELISA) demonstrated significant levels both in muscle and plasma.
      We observed a smaller cisplatin-related increase in the latency of the sensory
      nerve action potential of the caudal nerve in pCMVNT-3-treated mice than in
      controls (p < 0.0001). Mean sensory distal latencies were not different between
      the 5- and 50- microg/animal/injection groups. Treatment with gene therapy
      induced only a slight muscle toxicity and no general side effects. Therefore,
      neurotrophic factor delivery by direct gene transfer into muscle by
      electroporation is of potential benefit in the prevention of cisplatin-induced
      neuropathy and of peripheral neuropathies in general.

PMID- 11242530
TI  - Stable transduction with lentiviral vectors and amplification of immature
      hematopoietic progenitors from cord blood of preterm human fetuses.
AB  - Umbilical cord blood (CB) from the early gestational human fetus is recognized as
      a rich source of hematopoietic stem cells. To examine the value of fetal CB for
      gene therapy of inborn immunohematopoietic disorders, we tested the feasibility
      of genetic modification of CD34(+) cells from CB at weeks 24 to 34 of pregnancy,
      using lentiviral vector-mediated transfer of the green fluorescent protein (GFP)
      gene. The transduction rate of CD34(+) cells was 42 +/- 9%, resulting in GFP
      expression in 23 +/- 4% of colonies derived from colony-forming units (CFUs) and
      11 +/- 1% from primitive long-term culture-initiating cells (LTC-ICs). Cell cycle
      analysis demonstrated transduction and GFP expression in cells in the G(0) phase,
      which contains immature hematopoietic progenitors. Transduced fetal CD34(+) cells
      could be expanded 1000-fold in long-term cultures supplemented with megakaryocyte
      growth and development factor along with Flt-3 ligand. At week 10, expression of
      GFP was observed in 40.5 +/- 11.7% of CFU-derived colonies. While prestimulation
      of CD34(+) cells with cytokines prior to transduction increased the efficiency of
      GFP transfer 2- to 3-fold, long-term maintenance of GFP-expressing CFUs occurred
      only in the absence of prestimulation. The GFP gene was found integrated into the
      genomic DNA of 35% of LTC-IC-derived colonies initiated at week 10, but GFP
      expression was not detectable, suggesting downregulation of transgene activity
      during the extended culture period. These results indicate that human fetal CB
      progenitors are amenable to genetic modification by lentiviral vectors and may
      serve as a target for gene therapy of hematopoietic disorders by prenatal
      autologous transplantation.

PMID- 11242531
TI  - Adenoviral transduction efficiency of ovarian cancer cells can be limited by loss
      of integrin beta3 subunit expression and increased by reconstitution of integrin
      alphavbeta3.
AB  - Recombinant adenoviruses expressing a therapeutic gene are currently used in
      clinical studies for treatment of advanced ovarian cancer. We therefore tested
      whether the expression level of primary (CAR) and secondary adenovirus receptors
      (integrins) was predictive of the efficacy of adenoviral gene transfer in ovarian
      cancer cells. Adenoviral transduction efficiency (ATE) was determined with an E1
      deleted adenovirus type 5 expressing beta-galactosidase under a CMV promoter
      (AdGal). ATE was studied in relationship to the expression level of both CAR
      (coxsackie and adenovirus receptor) and integrins. A representative sample of 25
      permanent human cell lines established from advanced ovarian cancer in our
      laboratory and the OV-2774 cell line were tested. Overall, ATE increased with
      increasing titers of AdGal. At a given titer of 50 infectious units per cell,
      transduction efficiency varied from 6 to 94% among the individual cell lines. All
      cell lines expressed CAR and integrin alpha(v)beta(5), but no relation between
      ATE and expression level of CAR or alpha(v)beta(5) integrin was observed. In
      contrast, cell lines with poor ATE, despite expressing high levels of CAR, lacked
      expression of integrins alpha(v)beta(3) and alpha(5)beta(1). Reconstitution of
      alpha(v)beta(3) integrin by reexpressing the beta(3) subunit significantly
      enhanced ATE of ovarian cancer cells. In ovarian cancer, neither integrins nor
      CAR alone appear to be potentially useful predictive markers for ATE by serotype
      5 adenovirus in clinical gene therapy. A minimum level of CAR necessary for
      binding of adenoviruses was observed in all tested ovarian cancer cell lines.
      Loss of alpha(v)beta(3) integrin is frequently associated with advanced stages of
      ovarian cancer and can significantly reduce ATE.

PMID- 11242532
TI  - Efficient human immunodeficiency virus-based vector transduction of unstimulated
      human mobilized peripheral blood CD34+ cells in the SCID-hu Thy/Liv model of
      human T cell lymphopoiesis.
AB  - The methods available to efficiently transduce human CD34(+) hematopoietic stem
      cells (HSCs) derived from mobilized peripheral blood, such that they fully retain
      their engraftment potential and maintain high levels of transgene expression in
      vivo, have been unsatisfactory. The current murine retrovirus-based gene transfer
      systems require dividing cells for efficient transduction, and therefore the
      target HSCs must be activated ex vivo by cytokines to cycle, which may limit
      their engrafting ability. Lentivirus-based gene transfer systems do not require
      cell division and, thus, may allow for efficient gene transfer to human HSCs in
      the absence of any ex vivo cytokine stimulation. We constructed human
      immunodeficiency virus (HIV)-based vectors and compared them in vitro and in vivo
      with MuLV-based vectors in their ability to transduce unstimulated human CD34(+)
      HSCs isolated from mobilized peripheral blood. Both sets of vectors contained the
      marker gene that expresses the enhanced green fluorescent protein (EGFP) for
      evaluating transduction efficiency and were pseudotyped with either vesicular
      stomatitis virus glycoprotein (VSV-G) or the amphotropic murine leukemia virus
      envelope (A-MULV Env). The VSV-G-pseudotyped HIV-based vectors containing an
      internal mouse phosphoglycerate kinase promoter (PGK) were able to transduce up
      to 48% of the unstimulated CD34(+) cells as measured by EGFP expression. When
      these cells were injected into the human fetal thymus implants of irradiated SCID
      hu Thy/Liv mice, up to 18% expressed EGFP after 8 weeks in vivo. In contrast, the
      MULV-based vectors were effective at transducing HSCs only in the presence of
      cytokines. Our results demonstrate that the improved HIV-based gene transfer
      system can effectively transduce unstimulated human CD34(+) HSCs, which can then
      differentiate into thymocytes and provide long-term transgene expression in vivo.

PMID- 11242533
TI  - Long-term acceptance of allografts by in vivo gene transfer of regulatable
      adenovirus vector containing CTLA4IgG and loxP.
AB  - CTLA4IgG was shown to inhibit the costimulatory signal for T cell activation by
      interfering with the ligation of CD28 and B7-1 or B7-2. To inhibit various immune
      responses including acute cellular rejection of allografts, a certain level of
      serum CTLA4IgG should be maintained for an appropriate period. We previously
      reported on an adenovirus vector containing CTLA4IgG, which we designated
      Adex1CACTLA4IgG. Adex1CACTLA4IgG was able to maintain a significant level of
      serum CTLA4IgG for a long period on intravenous injection, which in turn
      inhibited various immune responses including protective immunity against
      infectious agents. To overcome the inhibitory effect, we constructed a new
      adenovirus vector, Adex1CALoxCTLA4IgGLox, by cloning CTLA4IgG cDNA between two
      loxP sequences under the control of the CAG promoter. We demonstrated that the
      administration of adenovirus vector containing Cre recombinase gene (Adex1CACre)
      at the desired time induced Cre-mediated recombination within a gene derived from
      Adex1CALoxCTLA4IgGLox vector, and the cDNA of CTLA4IgG was excised from the
      transduced gene and terminated the expression of CTLA4IgG in vitro and in vivo.
      More importantly, we also demonstrated that the long-term acceptance of
      allografts was achieved after the termination of CTLA4IgG expression, while the
      immune response against adenovirus was restored.

PMID- 11242534
TI  - Efficient expression of naked dna delivered intraarterially to limb muscles of
      nonhuman primates.
AB  - We have previously shown that the intraarterial delivery of naked plasmid DNA
      (pDNA) into the femoral artery of rats leads to high levels of foreign gene
      expression throughout the muscles of the hindlimb. The present study shows that
      the procedure can also enable high levels of foreign gene expression throughout
      the limb skeletal muscles in rhesus monkeys. The average luciferase expression in
      the target muscle was 991.5 +/- 187 ng/g for the arm and 1692 +/- 768 ng/g for
      the leg; compared with 780 ng/g in rat hindlimb. Large numbers of beta
      galactosidase-positive myofibers were found in both leg and arm muscles, ranging
      from less than 1% to more than 30% in various muscles, with an average of 6.9%.
      The nonhuman primates tolerated the procedure without significant adverse effects
      in skeletal muscles, arteries, or other organs. Other studies in immunosuppressed
      rats indicated that stable expression is possible. These results suggest that the
      procedure is likely to enable efficient and stable gene expression in human
      muscle without substantial toxicity.

PMID- 11242535
TI  - Modulating the fibrinolytic system of peripheral blood mononuclear cells with
      adenovirus.
AB  - Gene therapy utilizing leukocytes is an unexplored therapeutic strategy for
      targeting tissue-type plasminogen activator (t-PA) to fibrin and sites of
      inflammation. In this study, five cationic lipids were observed to enhance the
      adenovirus (Ad)-mediated expression of t-PA in human peripheral blood mononuclear
      cells (PBMCs) in a dose-dependent manner between 1000 and 15,000 lipid molecules
      per Ad particle (efficiency:LipofectAMINE > GenePORTER > Effectene > SuperFect >
      DMRIE-C). PBMCs treated with Ad/t-PA * LipofectAMINE complexes displayed elevated
      t-PA expression over a 4-day period and the t-PA-expressing cells facilitated the
      lysis of plasma clots in vitro. Functional and immunologic assays revealed that
      the Ad * LipofectAMINE infection protocol did not affect monocyte adhesion in
      vitro or elevate the expression of procoagulant activity, interleukin 8, or tumor
      necrosis factor alpha. The potential of this system was documented with an in
      vivo rat model system that involved the injection of lipopolysaccharide into the
      peritoneal cavity to induce an inflammatory response. Infusion of Ad/t-PA
      infected rat PBMCs into the vasculature of lipopolysaccharide-treated animals was
      found to increase local fibrinolytic activity by 4-fold. These data provide a
      framework for utilizing adenovirus to transfer genes into PBMCs.

PMID- 11242538
TI  - Cloning and functional analysis of SEL1L promoter region, a pancreas-specific
      gene.
AB  - We examined the promoter activity of SEL1L, the human ortholog of the C. elegans
      gene sel-1, a negative regulator of LIN-12/NOTCH receptor proteins. To understand
      the relation in SEL1L transcription pattern observed in different epithelial
      cells, we determined the transcription start site and sequenced the 5' flanking
      region. Sequence analysis revealed the presence of consensus promoter elements-
      GC boxes and a CAAT box--but the absence of a TATA motif. Potential binding sites
      for transcription factors that are involved in tissue-specific gene expression
      were identified, including: activator protein-2 (AP-2), hepatocyte nuclear factor
      3 (HNF3 beta), homeobox Nkx2-5 and GATA-1. Transcription activity of the TATA
      less SEL1L promoter was analyzed by transient transfection using luciferase
      reporter gene constructs. A core basal promoter of 302 bp was sufficient for
      constitutive promoter activity in all the cell types studied. This genomic
      fragment contains a CAAT and several GC boxes. The activity of the SEL1L promoter
      was considerably higher in mouse pancreatic beta cells (beta TC3) than in several
      human pancreatic neoplastic cell lines; an even greater reduction of its activity
      was observed in cells of nonpancreatic origin. These results suggest that SEL1L
      promoter may be a useful tool in gene therapy applications for pancreatic
      pathologies.

PMID- 11242539
TI  - Mouse connexin 45: genomic cloning and exon usage.
AB  - Connexin 45 is a gap junction protein that is prominent in early embryos and is
      widely expressed in many mature cell types. To elucidate its gene structure,
      expression, and regulation, we isolated mouse Cx45 genomic clones. Alignment of
      the genomic DNA and cDNA sequences revealed the presence of three exons and two
      introns. The first two exons contained only 5' untranslated sequences, while exon
      3 contained the remaining 5' UTR, the entire coding region, and the 3' UTR. An RT
      PCR with exon-specific primers was utilized to examine exon usage in F9 mouse
      embryonal carcinoma cells and adult mouse tissues. In all samples, PCR products
      amplified using exon 2/exon 3 or exon 3/exon 3 primer pairs were much more
      abundant than products produced using exon 1/exon 2 or exon 1/exon 3 primer
      pairs, suggesting that Cx45 mRNAs containing exon 1 were relatively rare compared
      with mRNAs containing the other exons. Rapid amplification of cDNA ends (5'-RACE)
      was performed using antisense primers from within exon 3 and template RNA
      prepared from F9 cells or from adult mouse kidney. We obtained multiple RACE
      products from both templates, including products that contained all three exons
      and were spliced identically to the cDNA. However, clones were also isolated
      (from kidney) that began within the region previously identified as intron 1 and
      continued upstream with a sequence identical to the cDNA, including splicing to
      exon 3. These results show that mouse Cx45 has a gene structure that differs from
      that of previously studied connexins and allows the production of heterogeneous
      Cx45 mRNAs with differing 5' UTRs. These differences might contribute to
      regulation of Cx45 protein levels by modulating mRNA stability or translational
      efficiency.

PMID- 11242540
TI  - Intradermal delivery of interleukin-12 plasmid DNA by in vivo electroporation.
AB  - Gene therapy depends on safe and efficient gene delivery. The skin is an
      attractive target for gene delivery because of its accessibility. Recently, in
      vivo electroporation has been shown to enhance expression after injection of
      plasmid DNA. In this study, we examined the use of electroporation to deliver
      plasmid DNA to cells of the skin in order to demonstrate that localized delivery
      can result in increased serum concentrations of a specific protein. Intradermal
      injection of a plasmid encoding luciferase resulted in low levels of expression.
      However, when injection was combined with electroporation, expression was
      significantly increased. When performing this procedure with a plasmid encoding
      interleukin-12, the induced serum concentrations of gamma-interferon were as much
      as 10 fold higher when electroporation was used. The results presented here
      demonstrate that electroporation can be used to augment the efficiency of direct
      injection of plasmid DNA to skin.

PMID- 11242541
TI  - Alterations in chromatin structure are implicated in the activation of the
      steroid hormone response unit of the ovalbumin gene.
AB  - Hormone-responsive genes rely on complex regulatory elements known as hormone
      response units to integrate various regulatory signals. Characterization of the
      steroid-dependent regulatory element (SDRE) in the check ovalbumin gene (--892 to
      --796) suggests that it functions as a hormone response unit. Previous studies
      using gel mobility shift assays and several types of footprinting analyses
      demonstrated that proteins bind to this entire element in vitro even in the
      absence of steroid hormones. However, the genomic footprinting experiments
      described herein indicate that the binding of three different proteins or protein
      complexes to the SDRE requires estrogen and corticosterone, suggesting that the
      chromatin structure of this site is restricted in vivo. Transfection experiments
      using linker scanning and point mutations support the contention that the binding
      of these three complexes is essential for induction of the ovalbumin gene by
      steroid hormones. In addition, functional analyses suggest that a fourth complex
      is also necessary for maximal induction. These and other data suggest that the
      SDRE functions as a hormone response unit to coordinate signals generated by two
      steroid hormones.

PMID- 11242542
TI  - Cloning and characterization of human WDR10, a novel gene located at 3q21
      encoding a WD-repeat protein that is highly expressed in pituitary and testis.
AB  - Members of the steroid-thyroid-retinoid receptor superfamily regulate a spectrum
      of cellular functions, including metabolism and growth and differentiation. We
      sought to isolate novel members of this family by using degenerate
      oligonucleotide primers directed to sequences encoding the AF-2 domain of these
      molecules in a PCR-based approach. The AF-2 domain serves a critical function in
      recruiting coregulatory molecules and in transcriptional activation. We report
      the cloning and initial characterization of a novel gene, WDR10, which encodes a
      140-kD protein that is highly expressed in pituitary and testis. This protein,
      WDR10p, contains an AF-2 domain as well as seven N-terminal WD repeats and is
      highly conserved through evolution. Chromosomal localization studies placed WDR10
      at 3q21, near a locus for the Moebius syndrome, Hailey-Hailey disease, and
      rhodopsin, which is involved in several forms of retinitis pigmentosa. The
      expression pattern of WDR10 and its chromosomal location makes this novel gene a
      candidate gene for the hypogonadism associated with some forms of retinitis
      pigmentosa and the Moebius syndrome.

PMID- 11242543
TI  - Gene structure for adenosine kinase in Chinese hamster and human: high-frequency
      mutants of CHO cells involve deletions of several introns and exons.
AB  - The structure for the adenosine kinase (AK) gene has been determined from Chinese
      hamster (CH) and human cells. The AK gene in CH is comprised of 11 exons ranging
      in length from 36 to 765 nt, with the majority <100 nt. The exact lengths of the
      intervening introns have not been determined, but most of them are indicated to
      be very large (>15 kb). A 6.6-kb fragment from human cells was also sequenced,
      and it contained only a single exon corresponding to exon 10 in CH. The BLAST
      searches of the subsequently released draft human genome sequence have revealed
      that the AK gene structure in human is identical to that in CH. In the human
      genome, the AK exons are distributed over four genomic clones totaling 752 kb,
      providing direct evidence that the AK gene in mammalian species is unusually
      large. In contrast to CH and human, the AK genes from several other eukaryotic
      organisms whose complete genomes are now known are quite small (between 1.2 and
      2.5 kb) and either contain no introns (Saccharomyces cerevisiae and
      Schizosaccharomyces pombe) or various numbers of introns (Drosophila melanogaster
      [2], Caenorhabditis elegans [4], Arabidopsis thaliana [10]). Some of the intron
      exon junctions in these species are in the same positions as in mammals. The AK
      gene in CH and human, as well as mouse, is linked upstream in a head-to-head
      fashion with the gene for the clathrin adaptor mu3 protein (or beta 3A subunit of
      the AP-3 protein complex), which is affected in type 2 Hermansky-Pudlak syndrome.
      These two genes are separated by <200 nt, and it is possible that they have a
      common or overlapping promoter(s). We have also determined the nature of the
      genetic alterations in two of the class A AK(-) mutants of CHO cells, which are
      obtained at a very high spontaneous frequency (10(-3)-10(-4)) in this cell line.
      Both mutants contained large deletions within the AK gene and greatly shortened
      AK transcripts. The cloning and sequencing of the transcripts from these mutants
      showed that the deletion in one of them led to the loss of exons 5 through 8,
      whereas in the other, all exons from 2 through 8 are deleted. The endpoints of
      these deletions lie in the large introns within the AK gene.

PMID- 11242544
TI  - Clinical trial of telepathology as an alternative modality in breast
      histopathology quality assurance.
AB  - Telepathology is a potential alternative to conventional histopathology. A
      clinical trial using a robotic telepathology system was conducted to assess the
      clinical and technical utility and effectiveness of telepathology in the U.K.
      breast screening pathology quality assurance program. Eighty-seven cases of
      breast disease were chosen at random from a series of 192 cases from the U.K.
      Breast Screening Pathology National Quality Assurance Scheme (NEQAS) collection.
      There were 20 benign, 23 carcinoma in situ (CIS), and 44 invasive malignant
      cases. The diagnostic accuracy of telepathology (TP) compared with conventional
      light microscopic (LM) diagnosis was 98.8%; this included a single case deferred
      for LM examination. The figure was similar when compared with expert consensus
      diagnosis (CD). In invasive tumor typing, TP accuracy was 95.4% (42/44 cases),
      the difference being attributable to slide color fading and would have had no
      impact on patient management. The accuracy of TP versus LM and expert consensus
      in tumor grading was 91.3% for carcinoma in situ (21/23 cases), a discordance
      with no relevance to patient management. TP grading of invasive tumor compared
      with LM diagnosis, had an accuracy of 86.4% (38/44) with a clinically significant
      accuracy of 97.7% (43/44). The time taken for TP diagnosis averaged 3.9 minutes
      per case by the end of the study. This data demonstrates that telepathology
      diagnostic accuracy is comparable to conventional microscopy and may therefore be
      envisaged as an alternative to conventional light microscopy for more rapid
      proficiency testing in breast screening (and perhaps other) quality assurance
      schemes.

PMID- 11242545
TI  - Evaluation of an asynchronous teleconsultation system for diagnosis of skin
      cancer and other skin diseases.
AB  - We wished to assess both diagnostic accuracy and concordance among dermatologists
      when evaluating digital images of skin disease presented using a low-cost
      asynchronous (store-and-forward) format. Each of eight board-certified
      dermatologists reviewed 50 clinical cases presented in digital format on a 15
      inch computer monitor. For each case, the teleconsultants made a primary
      diagnosis and differential diagnosis and indicated whether or not a biopsy should
      be performed both before and after reviewing a brief history of each case.
      Diagnostic accuracy was calculated for each teleconsultant on the basis of
      biopsy, culture, or wet mount results. Concordance was determined by comparing
      primary and differential diagnoses made by the teleconsultants on all 50 cases
      with those made by the dermatologists who originally examined the patients in
      person. For eight skin cancers, the diagnostic accuracy for the inperson
      dermatologist was 88% versus 90% (range, 75-100%) for the teleconsultants. For
      the 25 cases (including the 8 skin cancers) confirmed by either biopsy (20),
      culture (1), or wet mount (4), the in-person accuracy was 84% compared to 73%
      (range, 65-88%) for the teleconsultants. The concordance between the in-person
      and teleconsultant diagnoses were in agreement 77% of the time (90% if
      differential diagnoses were included). After evaluating the accompanying history,
      teleconsultants changed their primary diagnosis in 11% of the cases (range, 2
      22%). Biopsy rates were not significantly different between teleconsultants (45%)
      and in-person dermatologists (40%). An asynchronous software application can
      provide levels of diagnostic accuracy and concordance equivalent to those
      reported using live teleconsultation.

PMID- 11242546
TI  - Financial analysis of telecardiology used in a correctional setting.
AB  - The aim of this study is to evaluate the cost savings of 3 years of
      telecardiology used in a prison. This study compares the cost per visit of
      providing cardiology services by telemedicine (telecardiology) to patients at
      Powhatan Correctional Center of the Virginia Department of Corrections (PCC) and
      the cost of providing traditional cardiology services at the cardiology clinic of
      the Medical College of Virginia Campus of Virginia Commonwealth University (MCV
      Campus). During 1996 to 1998, telecardiology visits increased from 24 per year to
      86. In this study, lower use of telecardiology services in 1996 resulted in
      higher cost per visit of $189. This was $45 more than the cost of traditional
      cardiology in the cardiology clinic at the MCV Campus. In 1997 and 1998, however,
      higher utilization of telecardiology services decreased the cost per visit to
      $135 and $132, respectively. This resulted in a cost saving with telecardiology
      of $15 per visit in 1997 and $46 per visit in 1998. Because the vast proportion
      of telemedicine operating costs are fixed, increased utilization causes reduced
      cost per visit and results in a cost saving compared with providing these
      services via a non-telemedicine program.

PMID- 11242547
TI  - Improved rural provider access to continuing medical education through
      interactive videoconferencing.
AB  - We sought to describe use patterns and user evaluation of remotely-attended
      continuing medical education (CME) programs in Vermont and upstate New York.
      Remote attendees were required to return an evaluation form to receive CME
      credit. The form included name and date of the program; name, location, and
      specialty of the respondent; and questions regarding program quality, value,
      effectiveness, and attendee plans if the program had not been available via
      telemedicine. From April, 1996, through December, 1998, health care providers
      from 14 remote sites used the network 927 times to attend 394 CME programs at
      Fletcher Allen Health Care in Burlington, Vermont. After the start-up period, an
      average of over three programs per week was attended, with an average of 2.4
      remote attendees per program. Seventy-seven percent of remote attendees stated
      that they would not have attended the program if it had not been available over
      telemedicine, while the remaining 23% said that they avoided traveling due to
      videoconferencing. When asked the effectiveness of telemedicine technology for
      attending, 73% said it was as effective as having the presenter in the room, 23%
      said it was less effective, and 4% said it was more effective. Major technical
      problems, such as having the call disconnect during the presentation, decreased
      over time. There were continuing minor logistical problems common to large group
      videoconferencing. The telemedicine system has increased availability of CME
      programs for rural providers in Vermont and upstate New York. Most attendees have
      found the programs to be worthwhile, and technological advancements have improved
      the quality of the system.

PMID- 11242548
TI  - Telephone management in substance abuse treatment.
AB  - The purpose of this article is to describe the results of a clinical trial in
      which telephonic case management was evaluated as a supplement to substance abuse
      treatment. An interactive voice response system (IVR) was developed by the
      research team for use in the case management of randomly assigned participants in
      a clinical trial research project. The features of the software program
      facilitated a double caseload for the case manager as well as real-time data
      capture. At intake, no significant differences were found between participants in
      the telecommunication condition and the general project. Thus, the effectiveness
      of random assignment was supported. An IVR was useful for case management
      services, was less costly, and showed acceptability to clients. A reduction in
      time expenditure by using telecommunication occurred within three activity areas.
      Telecommunication facilitated client interaction and the use of case management,
      and it reduced provider time expenditure. As an alternative strategy,
      telecommunication case management can enhance cost effectiveness improvements.

PMID- 11242549
TI  - Patients' perceptions regarding home telecare.
AB  - While home telecare's potential to reduce health care costs appears clear,
      patients' perceptions regarding this new technology have not been studied. We
      conducted structured interviews to elicit patients' perceptions regarding home
      telecare. We developed a 34-item survey instrument, which was administered during
      structured home interviews to a convenience sample of patients who were currently
      or had previously been enrolled in the Sonora Health System or University of
      California Davis home telecare pilot projects. Fifteen (56%) of the 27 past or
      present enrollees agreed to be interviewed. Most had either a neutral (9 of 15,
      60%) or positive (5 of 15, 33%) outlook regarding home telecare before their
      enrollment. Following enrollment, all were either very satisfied (10 of 15, 67%)
      or somewhat satisfied (5 of 15, 33%) with services they had received. Fourteen of
      15 (93%) were willing to receive home telecare services in the future, and all 15
      would recommend home telecare to friends or family members. Despite education to
      the contrary, patients perceived that the presence of telecare equipment in the
      home implied 24-hour-a-day access to a nurse. Some interviewees felt
      uncomfortable disclosing intimate information during televisits, and others
      lamented the reduced amount of time nurses spent "socializing" as compared to in
      person visits. Despite concerns regarding its confidentiality and its ability to
      approximate the social stimulation of in-person nursing visits, patients in these
      pilot trials seemed satisfied with home telecare and appeared ready to accept its
      widespread use.

PMID- 11242550
TI  - Telemedicine and patient satisfaction: current status and future directions.
AB  - One of the most researched areas in telemedicine concerns the issue of
      satisfaction. However, most of this research lacks any consistent methodological
      approach. As a result, it is difficult to conclude whether patients and providers
      are satisfied with telemedicine. However, this paper postulates that there is a
      bigger problem within the satisfaction literature than the quality of the
      research to date. Instead, the bigger question is whether the results from a
      specific telemedicine project can actually be generalized across all telemedicine
      contexts. This paper argues that research should focus on specific questions of
      interest rather than continue the tradition of generic satisfaction research if
      we hope to gain specific knowledge that will inform the field of telemedicine as
      a whole.

PMID- 11242551
TI  - Residency training via videoconference--satisfaction survey.

PMID- 11242552
TI  - Licensing telemedicine: the need for a national system.
AB  - The expansion of information technology has shattered geographic boundaries,
      allowing for extraordinarily increased access to health information and expanded
      opportunities for telemedicine practice across state boundaries. But despite its
      recent growth, telemedicine technology remains embedded in a state-based
      licensure system that places severe limits on its expansion. The current system
      of medical licensure is based primarily on statutes written at the turn of the
      20th century. This system is inadequate to address the emerging medical practices
      and future uses of medical technology in the telecommunications age. To respond
      to the changes offered by the telecommunications revolution, we need to design a
      new regulatory structure for the 21st century. The purpose of this article is to
      propose a policy of national telemedicine licensure. The primary goal here is not
      to simply develop a policy proposal, but to discuss the rationale for national
      licensure and place it on the policy agenda. A national licensure system will
      expand the market for telemedicine, promote both the use and development of new
      technologies, and simultaneously eliminate many of the legal and regulatory
      ambiguities that plague and constrain the present system.

PMID- 11242553
TI  - A strategic vision for telemedicine and medical informatics in space flight.
AB  - This Workshop was designed to assist in the ongoing development and application
      of telemedicine and medical informatics to support extended space flight.
      Participants included specialists in telemedicine and medical/health informatics
      (terrestrial and space) medicine from NASA, federal agencies, academic centers,
      and research and development institutions located in the United States and
      several other countries. The participants in the working groups developed vision
      statements, requirements, approaches, and recommendations pertaining to
      developing and implementing a strategy pertaining to telemedicine and medical
      informatics. Although some of the conclusions and recommendations reflect ongoing
      work at NASA, others provided new insight and direction that may require a
      reprioritization of current NASA efforts in telemedicine and medical informatics.
      This, however, was the goal of the Workshop. NASA is seeking other perspectives
      and views from leading practitioners in the fields of telemedicine and medical
      informatics to invigorate an essential and high-priority component of the
      International Space Station and future extended exploration missions. Subsequent
      workshops will further define and refine the general findings and recommendations
      achieved here. NASA's ultimate aim is to build a sound telemedicine and medical
      informatics operational system to provide the best medical care available for
      astronauts going to Mars and beyond.

PMID- 11242554
TI  - System of telemedicine services designed for family doctors' practices.
AB  - The main goal of the most European telemedicine programs is to increase access to
      emergency and primary care; however, telemedicine presents both profound
      opportunities and challenges to general practice/family medicine. The aim of this
      project is to develop and demonstrate a regional primary care teleconsulting
      system in Poland linking an academic family medicine center and 10 family
      doctors' practices (both urban and rural) within a range of 100-200 km, serving a
      local population of 25,000 individuals. It is designed to support real-time
      consultations among health care providers via a computer network, provide secure
      access to multimedia patient records, and facilitate an innovative home
      monitoring and remote care from doctors to their patients. The entire process
      (planned for 3 years) includes: selecting the best technology (i.e.,
      teletransmission system, communication protocols, etc.) and equipment; preparing
      the assumptions and conditions for formats and transmission rates; analysis of
      the existing techniques of compression and preparing own specific solution;
      finding an optimal infrastructure (i.e., equipment and communication
      configuration); implementing the system; evaluation of the medical, economic,
      organizational, and sociological aspects of the system (i.e., accessibility to
      primary health care, cost feasibility and cost-effectiveness of telemedicine
      services, quality of care assessment, etc.). The project offers the potential to
      improve: access to high-quality primary health care; the patient-physician bond
      and the attending physician's level of confidence; education of family doctors;
      use of expensive resources; and a convenient mode of delivering medical services
      to the patient.

PMID- 11242555
TI  - Chronic Coronary Occlusions.
AB  - The goal of management of chronic coronary occlusions is primarily the relief of
      cardiac ischemic symptoms. This may be achieved through the use of medical
      therapy, recanalization by percutaneous endovascular intervention or coronary
      artery bypass grafting (CABG). Recanalization of the occluded vessel also may
      have the additional benefits of improved cardiac function and long-term survival.

PMID- 11242556
TI  - Right Ventricular Infarction.
AB  - Right ventricular (RV) ischemia occurs in a substantial proportion of patients
      with acute inferior myocardial infarction (MI), and may result in severe
      hemodynamic compromise. This defines a high-risk subset of patients with a
      mortality rate of 25% to 30%, as opposed to an overall mortality rate of
      approximately 6% patients with inferior MI without right ventricular infarction
      (RVI). Early recognition of RV ischemic dysfunction is of great importance in
      inferior MI with clinical evidence of low cardiac output, because the therapeutic
      approaches are very different from that for cardiogenic shock resulting
      predominantly from severe left ventricular (LV) failure. Management of RV
      ischemic dysfunction includes maintenance of RV preload with volume loading and
      maintenance of atrioventricular synchrony, inotropic support, and reduction of RV
      afterload in the setting of LV dysfunction. Reperfusion therapy should be
      initiated in patients with RV ischemic dysfunction. Though the RV appears to be
      relatively resistant to infarction and has a remarkable ability to recover even
      after prolonged occlusion, successful reperfusion of the right coronary artery
      and major RV branches rapidly improves RV ejection fraction and hemodynamic
      status, and decreases in-hospital mortality and morbidity.

PMID- 11242557
TI  - Restenosis after Angioplasty.
AB  - Angiographic restenosis occurs in 30% to 50% of patients after percutaneous
      transluminal coronary angioplasty (PTCA) with 20% to 30% target vessel
      revascularization at one year, and is associated with increased morbidity,
      mortality and health care costs. Intracoronary stents are the first line of
      therapy against restenosis after angioplasty. Depending on lesion morphology and
      location, stents can reduce restenosis and target lesion revascularization (TLR)
      by 20% to 30%. Obstructive coronary lesions in vessels with a diameter larger
      than 3.0 mm should be stented. The benefit of stenting in vessels smaller than
      3.0 mm is controversial, with the BESMART (Bestent in Small Arteries) and ISAR
      SMART (Intracoronary Stenting or Angioplasty for Restenosis Reduction in Small
      Arteries) studies demonstrating conflicting results. Chronically occluded and
      subtotal vessels should be stented after PTCA. Obstructive lesions in saphenous
      vein grafts should be stented. It is preferable to stent ostial lesions after
      PTCA. Restenosis can occur in 15% to 25% of patients within 6 months of stent
      placement. Initial approach to focal in-stent restenosis is to repeat PTCA.
      Patients with diffuse restenosis may require debulking prior to PTCA to improve
      acute results. "Stenting within-stent" has not proven beneficial unless there is
      diffuse in-stent restenosis, neointimal prolapse or vessel dissection during
      PTCA. There are no pharmacologic therapies approved by the Food and Drug
      Administration available to treat restenosis at present. Brachytherapy, gamma or
      beta, is an effective adjunctive therapy that can reduce recurrent in-stent
      restenosis by 40% to 70%. Patients at high risk for recurrent in-stent restenosis
      (proliferative or total occlusion pattern) can be considered for brachytherapy to
      treat the first episode of in-stent restenosis. Patients with focal in-stent
      restenosis should be treated with brachytherapy after multiple recurrences of in
      stent restenosis. Emerging therapies for treatment of restenosis include
      antiproliferative-coated stents and photoangioplasty.

PMID- 11242558
TI  - Secondary Pulmonary Hypertension.
AB  - The diagnosis of pulmonary hypertension first requires a clinical suspicion, as
      symptoms are often nonspecific. After the diagnosis is made, appropriate
      classification into the various categories of pulmonary hypertension is essential
      in order to manage the patient's disease and symptoms appropriately. Therapy is
      targeted at the underlying cause of the pulmonary hypertension, as well as its
      effects on the cardiovascular system. Until recently, the treatment of both
      primary and secondary pulmonary arterial hypertension was limited to supportive
      therapy alone. With the advent of novel therapeutic agents, more focused
      therapies designed to treat the pulmonary vasculopathy have become available.
      These include pulmonary vasodilators such as continuous intravenous prostacyclin,
      and experimental agents currently undergoing clinical trials. For patients with
      pulmonary hypertension secondary to pulmonary venous hypertension, therapies
      differ. In cases where there is left-sided heart disease leading to pulmonary
      venous hypertension, treatment is aimed at repairing or ameliorating the
      underlying heart disease. Patients with pulmonary venous hypertension due to
      extrinsic compression of the central pulmonary veins, or pulmonary veno-occlusive
      disease have few options, and treatment is generally palliative. In patients with
      pulmonary hypertension that is associated with disorders of the respiratory
      system or hypoxemia, the pulmonary hypertension is due to a reactive pulmonary
      vasoconstriction. Reversal of this vasoconstriction with pulmonary vasodilators
      can be harmful because of the risk of increasing perfusion to nonventilated lung
      units. Pulmonary hypertension due to chronic thrombotic or embolic disease can be
      treated surgically, if the obstructive thrombi are proximal enough for the
      surgeon to resect them. More distal pulmonary emboli, however, cannot be
      resected, but there is emerging evidence that the chronic administration of
      pulmonary vasodilators can be effective in treating this form of the disease.

PMID- 11242559
TI  - Cardiopulmonary Complications Following Cardiac Surgery.
AB  - There are numerous cardiac and pulmonary complications that can occur after
      operations that involve the use of cardiopulmonary bypass (CPB). We have chosen
      to focus on perioperative myocardial ischemia, left ventricular (LV) dysfunction,
      ventricular arrhythmias, atrial arrhythmias, and inflammation and pulmonary
      dysfunction as the most important. If left untreated, these complications can be
      life-threatening. Moreover, their presence is associated with higher hospital
      expenses due to therapies and longer inpatient stays.

PMID- 11242560
TI  - Acute and Chronic Pulmonary Emboli.
AB  - Under most circumstances, the goal of treatment of pulmonary embolism is the
      prevention of recurrent embolic events, achieved through conventional
      anticoagulant therapy with unfractionated heparin or a low molecular weight
      heparin, followed by warfarin therapy for a minimum of 6 months. When acute
      pulmonary embolism is associated with significant right ventricular dysfunction
      or systemic hypotension, more aggressive intervention may be warranted. Under
      these circumstances, potential interventions include thrombolytic therapy (either
      systemic or catheter-directed), placement of an inferior vena caval filter,
      catheter-based embolectomy, or surgical embolectomy. Chronic thromboembolic
      pulmonary hypertension may develop in a small minority of patients who survive an
      acute, massive embolic event or who have suffered recurrent thromboembolic
      events. Due to the fixed nature of the pulmonary vascular obstruction,
      vasodilator therapy has proven far less effective in chronic thromboembolic
      disease than it has in primary pulmonary hypertension and other secondary forms
      of pulmonary hypertension. Correction of hypoxemia and volume overload and the
      prevention of recurrent embolic events are essential. Definitive therapy,
      however, requires surgical intervention to remove the chronic thromboembolic
      obstruction and to restore patency of the pulmonary vascular bed.

PMID- 11242561
TI  - High Output Cardiac Failure.
AB  - Congestive heart failure describes a syndrome with complex and variable symptoms
      and signs, including dyspnea, increased fatigability, tachypnea, tachycardia,
      pulmonary rales, and peripheral edema. Although this syndrome usually is
      associated with low cardiac output, it may occur in a number of so-called high
      output states, when the cardiac output is normal or greater than normal. A high
      output state may occur in chronic severe anemia, large arteriovenous fistula or
      multiple small arteriovenous shunts as in Paget's bone disease, some forms of
      severe hepatic or renal disorders, and acutely in septic shock. The syndrome of
      systemic congestion in a high output state is traditionally referred to as high
      output heart failure. However, the term is a misnomer because the heart in these
      conditions is normal, capable of generating very high cardiac output. The
      underlying problem in high output failure is a decrease in the systemic vascular
      resistance that threatens the arterial blood pressure and causes activation of
      neurohormones, resulting in an increase in salt and water retention by the
      kidney. Many of the high output states are curable conditions, and because they
      are associated with decreased peripheral vascular resistance, the use of
      vasodilator therapy for treatment of congestion may aggravate the problem. There
      are other clinically important issues in high output failure that have received
      little attention in the current medical literature. This article reviews the
      available data on high output cardiac failure with particular emphasis on the
      underlying mechanisms and treatment.

PMID- 11242562
TI  - UAG readthrough in mammalian cells: effect of upstream and downstream stop codon
      contexts reveal different signals.
AB  - BACKGROUND: Translation termination is mediated through an interaction between
      the release factors eRF1 and eRF3 and the stop codon within its nucleotide
      context. Although it is well known that the nucleotide contexts both upstream and
      downstream of the stop codon, can modulate readthrough, little is known about the
      mechanisms involved. RESULTS: We have performed an in vivo analysis of
      translational readthrough in mouse cells in culture using a reporter system that
      allows the measurement of readthrough levels as low as 10(-4). We first
      quantified readthrough frequencies obtained with constructs carrying different
      codons (two Gln, two His and four Gly) immediately upstream of the stop codon.
      There was no effect of amino acid identity or codon frequency. However, an
      adenine in the -1 position was always associated with the highest readthrough
      levels while an uracil was always associated with the lowest readthrough levels.
      This could be due to an effect mediated either by the nucleotide itself or by the
      P-site tRNA. We then examined the importance of the downstream context using
      eight other constructs. No direct correlation between the +6 nucleotide and
      readthrough efficiency was observed. CONCLUSIONS: We conclude that, in mouse
      cells, the upstream and downstream stop codon contexts affect readthrough via
      different mechanisms, suggesting that complex interactions take place between the
      mRNA and the various components of the translation termination machinery.
      Comparison of our results with those previously obtained in plant cells and in
      yeast, strongly suggests that the mechanisms involved in stop codon recognition
      are conserved among eukaryotes.

PMID- 11242563
TI  - Cholinergic and GABAergic pathways in fly motion vision.
AB  - BACKGROUND: The fly visual system is a highly ordered brain structure with well
      established physiological and behavioral functions. A large number of
      interneurons in the posterior part of the third visual neuropil, the lobula plate
      tangential cells (LPTCs), respond to visual motion stimuli. In these cells the
      mechanism of motion detection has been studied in great detail. Nevertheless, the
      cellular computations leading to their directionally selective responses are not
      yet fully understood. Earlier studies addressed the neuropharmacological basis of
      the motion response in lobula plate interneurons. In the present study we
      investigated the distribution of the respective neurotransmitter receptors in the
      fly visual system, namely nicotinic acetylcholine receptors (nAChRs) and GABA
      receptors (GABARs) demonstrated by antibody labeling. RESULTS: The medulla shows
      a laminar distribution of both nAChRs and GABARs. Both receptor types are present
      in layers that participate in motion processing. The lobula also shows a
      characteristic layering of immunoreactivity for either receptor in its posterior
      portion. Furthermore, immunostaining for nAChRs and GABARs can be observed in
      close vicinity of lobula plate tangential cells. Immunostaining of GABAergic
      fibers suggests that inhibitory inputs from the medulla are relayed through the
      lobula to the lobula plate rather than through direct connections between medulla
      and lobula plate. CONCLUSIONS: The interaction of excitatory and inhibitory
      pathways is essential for the computation of visual motion responses and
      discussed in the context of the Reichardt model for motion detection.

PMID- 11242565
TI  - Are qualitative studies of the PBL tutorial process indicated?

PMID- 11242566
TI  - Conveying emotional realism: a challenge to using standardized patients.

PMID- 11242567
TI  - The "jamais-vu phenomenon" in medical education.

PMID- 11242564
TI  - Plasma lipases and lipid transfer proteins increase phospholipid but not free
      cholesterol transfer from lipid emulsion to high density lipoproteins.
AB  - BACKGROUND: Plasma lipases and lipid transfer proteins are involved in the
      generation and speciation of high density lipoproteins. In this study we have
      examined the influence of plasma lipases and lipid transfer protein activities on
      the transfer of free cholesterol (FC) and phospholipids (PL) from lipid emulsion
      to human, rat and mouse lipoproteins. The effect of the lipases was verified by
      incubation of labeled (3H-FC,14C-PL) triglyceride rich emulsion with human plasma
      (control, post-heparin and post-heparin plus lipase inhibitor), rat plasma
      (control and post-heparin) and by the injection of the labeled lipid emulsion
      into control and heparinized functionally hepatectomized rats. RESULTS: In vitro,
      the lipase enriched plasma stimulated significantly the transfer of 14C-PL from
      emulsion to high density lipoprotein (p<0.001) but did not modify the transfer of
      3H-FC. In hepatectomized rats, heparin stimulation of intravascular lipolysis
      increased the plasma removal of 14C-PL and the amount of 14C-PL found in the low
      density lipoprotein density fraction but not in the high density lipoprotein
      density fraction. The in vitro and in vivo experiments showed that free
      cholesterol and phospholipids were transferred from lipid emulsion to plasma
      lipoproteins independently from each other. The incubation of human plasma,
      control and control plus monoclonal antibody anti-cholesteryl ester transfer
      protein (CETP), with 14C-PL emulsion showed that CETP increases 14C-PL transfer
      to human HDL, since its partial inhibition by the anti-CETP antibody reduced
      significantly the 14C-PL transfer (p<0.05). However, comparing the nontransgenic
      (no CETP activity) with the CETP transgenic mouse plasma, no effect of CETP on
      the 14C-PL distribution in mice lipoproteins was observed. CONCLUSIONS: It is
      concluded that: 1-intravascular lipases stimulate phospholipid transfer protein
      mediated phospholipid transfer, but not free cholesterol, from triglyceride rich
      particles to human high density lipoproteins and rat low density lipoproteins and
      high density lipoproteins; 2-free cholesterol and phospholipids are transferred
      from triglyceride rich particles to plasma lipoproteins by distinct mechanisms,
      and 3 - CETP also contributes to phospholipid transfer activity in human plasma
      but not in transgenic mice plasma, a species which has high levels of the
      specific phospholipid transfer protein activity.

PMID- 11242568
TI  - The RN shortage: not just nursing's problem.

PMID- 11242569
TI  - Alternative medicine: the importance of evidence in medicine and in medical
      education. Is there wheat among the chaff?

PMID- 11242570
TI  - How should alternative medicine be taught to medical students and physicians?
AB  - Advocates of alternative medicine are critical of current medical curricula, and
      have proposed fundamental changes, including the introduction of "integrative
      medicine" programs to teach alternative medicine. Medical educators have not
      replied to these criticisms, and have not developed basic curricula in
      alternative medicine. The author analyzes the alleged deficiencies in medical
      education, which are based on misrepresentations of medicine and medical
      training. (For example, critics state that physicians ignore mind-body
      interactions; in response, several examples are given to show that training
      physicians to consider the whole person and to identify and address emotional and
      social problems-the biopsycho-social model-are central tenets of medical
      education.) The author also examines fundamental differences between traditional
      and alternative medicine (e.g., their different attitudes toward the importance
      of evidence; the vitalistic versus the biomedical models of health and disease)
      that are central to the issue of how alternative medicine should be taught. He
      concludes that physicians need additional education in order to provide guidance
      to patients, but teaching about alternative medicine should be evidence-based,
      not merely the transmission of unproven practices.

PMID- 11242571
TI  - The never-ending search.

PMID- 11242572
TI  - Alternative medicine and common errors of reasoning.
AB  - Why do so many otherwise intelligent patients and therapists pay considerable
      sums for products and therapies of alternative medicine, even though most of
      these either are known to be useless or dangerous or have not been subjected to
      rigorous scientific testing? The author proposes a number of reasons this occurs:
      (1) Social and cultural reasons (e.g., many citizens' inability to make an
      informed choice about a health care product; anti-scientific attitudes meshed
      with New Age mysticism; vigorous marketing and extravagant claims; dislike of the
      delivery of scientific biomedicine; belief in the superiority of "natural"
      products); (2) psychological reasons (e.g., the will to believe; logical errors
      of judgment; wishful thinking, and "demand characteristics"); (3) the illusion
      that an ineffective therapy works, when actually other factors were at work
      (e.g., the natural course or cyclic nature of the disease; the placebo effect;
      spontaneous remission; misdiagnosis). The author concludes by acknowledging that
      when people become sick, any promise of a cure is beguiling. But he cautions
      potential clients of alternative treatments to be suspicious if those treatments
      are not supported by reliable scientific research (criteria are listed), if the
      "evidence" for a treatment's worth consists of anecdotes, testimonials, or self
      published literature, and if the practitioner has a pseudoscientific or
      conspiracy-laden approach, or promotes cures that sound "too good to be true."

PMID- 11242573
TI  - The importance of using scientific principles in the development of medicinal
      agents from plants.
AB  - The authors review the major scientific milestones and the legislative framework
      that have made possible the spectacular successes of many modern therapies that
      trace their origins to plants. They emphasize that drugs used in mainstream
      medicine, in contrast to most of those used in alternative medicine, are required
      to meet stringent federal requirements for purity, safety, and efficacy before
      they can be distributed to the public, and that the necessary testing requires
      much time and effort. Yet alternative medicines based on plant substances are
      extremely popular, even though their safety and efficacy have not been
      scientifically proven. Reasons for this are reviewed and numerous examples and
      case histories are cited illustrating both successes in the scientific
      development of drugs from plants and the dangers of unregulated drugs. Such drugs
      are more easily available because of the deregulating effect of the 1994 Dietary
      Supplement Health and Education Act (DSHEA), which has substantially weakened the
      authority of the Food and Drug Administration to ensure the safety of dietary
      supplements. The authors describe the rigorous scientific investigations of
      curcumin, from the ginger family, and of sulforaphane, from crucifers, to
      illustrate the long and demanding scientific process that is required to
      establish the safety and effectiveness of potential drugs from plants. They re
      emphasize the necessity for strict scientific review of all drugs. They also
      recommend that all providers of care be required to question patients about their
      intakes of dietary supplements. The authors close by saying that the DSHEA is "a
      disaster waiting to happen," but warn that any attempts to strengthen current
      legislation will be opposed by special interests.

PMID- 11242574
TI  - The need for educational reform in teaching about alternative therapies.
AB  - Advocacy and non-critical assessment are the approaches currently taken by most
      U.S. medical schools in their courses covering what is commonly called
      "complementary and alternative medicine" (CAM). CAM therapies are anomalous
      practices for which claims of efficacy are either unproved or disproved. The
      author's research indicates that most medical schools do not present CAM material
      in a form that encourages critiques and analyses of these claims. He presents the
      reasons for the unwarranted acceptance of CAM. These include the CAM movement's
      attempt to alter standards of evaluating therapies. A survey of CAM curricula in
      U.S. medical schools in 1995-1997 showed that of 56 course offerings related to
      CAM, only four were oriented to criticism. The author's course at Stanford
      University School of Medicine approaches CAM with the skepticism and critical
      thinking appropriate for unproven therapies. The author concludes by calling on
      all medical schools to include in their curricula methods to analyze and assess
      critically the content validity of CAM claims.

PMID- 11242575
TI  - The growing need to teach about complementary and alternative medicine: questions
      and challenges.
AB  - With the increased popularity of complementary and alternative medicine (CAM),
      there is a growing interest in the topic among physicians, residents, and medical
      students, who feel an increased need to have proper instruction about CAM
      therapies. Medical schools and residency programs are starting to respond to this
      demand, having realized that to provide better care and foster an improved
      patient-doctor relationship, physicians should become informed consultants, and
      be able to provide educated advice about CAM to their patients and help them
      integrate any CAM therapies shown to be safe and effective into their health
      care. The authors acknowledge that opinions differ about the adequacy of research
      findings to certify the safety and efficacy of specific therapies, and stress
      that physicians' decisions about CAM use should be subject to the same exacting
      criteria employed by researchers to evaluate any new therapies. The authors
      report on CAM curriculum developments in Germany, Canada, and the United States
      that illustrate various approaches to the question, "What should be taught in a
      CAM course?" In most cases, the approach is to teach about CAM therapies,
      although in others, therapies that the curriculum planners considered useful and
      safe are being integrated into the medical curriculum.

PMID- 11242577
TI  - Medicine and the arts.

PMID- 11242576
TI  - Medical education and television. 1951.

PMID- 11242579
TI  - Understanding the careers of physician educators in family medicine.
AB  - PURPOSE: Little is known about what contributes to the career decisions of
      physician educators in family medicine. This study sought to understand the
      variables that influence these decisions and to identify key sources of vitality
      for physician educators in family medicine. METHOD: A national sample of randomly
      selected physician educators in family medicine responded to a postcard survey
      regarding their contribution(s) to education and career satisfaction. A series of
      exclusion criteria were applied to 399 useable responses, yielding 24 physician
      educators who participated in a semi-structured telephone interview focusing on
      their careers. Using qualitative research methods, themes were identified and
      categorized from the transcribed interviews and investigators' field notes.
      RESULTS: The career decisions and actions of physician educators in family
      medicine emanated from an underlying set of values and beliefs associated with
      "making the world better." Participants sought challenging, diverse, and
      stimulating positions from which they could have an impact in ways that were
      consistent with their values. Three major sources of vitality (learners,
      colleagues, and patients) complemented the desire for challenging positions.
      Physician educators in family medicine, however, continually struggled to balance
      their personal and professional lives. CONCLUSION: The study results highlight
      the key variables that draw faculty into education and sustain their vitality,
      and the professional and personal challenges that can derail or support their
      careers. This information can be used to recruit, develop, and retain successful
      and productive physician educators in family medicine.

PMID- 11242580
TI  - Impact of a compliance program for billing on internal medicine faculty's
      documentation practices and productivity.
AB  - PURPOSE: Academic health centers and faculty practice plans have implemented
      programs to comply with Office of Inspector General (OIG) billing regulations.
      This study measured the impact of such a program on physicians' billing
      practices, faculty productivity, and operating revenues. METHOD: A prospective
      two-year study of departmental billing activities was carried out in 1997-98 and
      1998-99 in the department of internal medicine at the Saint Louis University
      School of Medicine and its faculty practice plan. Compliance with inpatient
      evaluation and management (E/M) coding and Health Care Financing Administration
      (HCFA) billing was evaluated by an independent staff of experts. Beginning in
      1998-99, the department provided detailed monthly reports of and education in
      billing and compliance performance to divisional managers and individual faculty.
      RESULTS: Inpatient admission profiles, practice patterns, and payer mixes of the
      faculty practice plan and department did not differ during the study. The gross
      collection rates for the practice and the department rose by 7.3% and 9.5%,
      respectively, and all divisions increased in their gross collection rates in 1998
      99. All but one division increased E/M services in 1998-99 (range -4% to +151%).
      All divisions decreased their rates of unbillable E/M services in 1998-99. The
      two divisions with the highest unbillable rates in 1997-98 (gastroenterology and
      cardiology) significantly reduced their unbillable service rates in 1998-99 (
      7.74% and -7.17%, respectively). Medical oncology and geriatrics recorded the
      greatest reductions in 1998-99 (-63% and -52%, respectively). All but two
      divisions increased the percentages of complex inpatient E/M services in 1998-99
      (average = +27.4%), with commensurate reductions in less complex visits (p <
      0.05), and there was an inverse correlation (R = -0.85; p < 0.01) between the
      relative increases in the division's inpatient encounters and the service
      complexity charged. A modest inverse correlation (R = -0.50; p < 0.05) existed
      between the reduction of relative percentages in divisions' unbillable rates
      (averaging -34%) and the increase in their gross collection rates (averaging +
      31%). CONCLUSION: Implementation of a billing compliance program at the
      departmental level enhances physician productivity and billing compliance for
      inpatient E/M services, potentially increasing departmental revenues while
      reducing the institutional risk of an OIG audit.

PMID- 11242581
TI  - Insights from outstanding rural internal medicine residency rotations at the
      University of Washington.
AB  - PURPOSE: Despite being well suited to provide the breadth of care needed in rural
      areas, few general internists become rural physicians. Little formal rural
      residency training is available and no formal curricula exist. For over 25 years
      the University of Washington School of Medicine has provided elective WWAMI
      (Washington, Wyoming, Alaska, Montana, Idaho) rural residency rotations to expose
      residents to the rewards and challenges of rural practice. This study identified
      the characteristics of outstanding rural residency rotations. METHOD: The key
      preceptors at three outstanding rural residency sites were interviewed about
      their experiences, teaching strategies, and opinions about curriculum. Their
      responses were categorized. Seven university-based residents and eight training
      at WWAMI sites recorded and rated the value of over 1,500 learning encounters.
      RESULTS: The preceptors agreed that outstanding rotations were led by
      enthusiastic preceptors who served as role models for excellence. These
      preceptors provided residents with meaningful responsibilities and emphasized
      independent decision making based on the history and physical examination. They
      stressed supervised independence and self-directed learning with frequent
      structured feedback for residents. The residents rated the learning value of
      patient encounters in rural locations significantly higher than that of those in
      university clinics. CONCLUSIONS: Exceptional rural residency experiences involve
      excellent role models who provide meaningful responsibility and emphasize core
      skills using a learner-centered approach. Rural training experiences should be
      supported, and the suggestions of outstanding preceptors should be used to
      develop and disseminate a curriculum that will better prepare residents for rural
      practice.

PMID- 11242582
TI  - Ageism in medical students' treatment recommendations: the example of breast
      conserving procedures.
AB  - PURPOSE: Age bias may play a role in physicians' discussions of equivalent
      therapeutic options with patients, especially in respect to breast-conservation
      therapy. This study investigated bias based on age (ageism) among physicians-in
      training in their treatment recommendations for breast-conserving procedures.
      METHOD: Second-year medical students responded to a questionnaire concerning
      recommendations they would make for breast conservation or mastectomies with or
      without breast reconstruction for eight patients with similar-stage breast
      cancer. The patients differed by age (older were > or =59 years, younger < or =31
      years), race, and marital status. A total of 116 students made 1,146
      recommendations. Percentages of the students' recommendations for breast
      conservation therapy (BCT) were calculated for the two patient age groups and for
      the recommendations for breast reconstruction after the patient had already
      chosen modified radical mastectomy (MRM). Chi-square tests were used for
      statistical analysis. RESULTS: The students recommended BCT for a significantly
      higher percentage of younger patients than older patients (86% versus 66%;
      p<.001). They recommended MRM to 34% of older patients versus 14% of younger
      patients (p<.001). Furthermore, the students recommended breast reconstruction
      after MRM to a significantly higher percentage of younger patients than older
      patients (95% versus 65%; p<.001). CONCLUSIONS: Medical students' recommendations
      of breast conservation and breast reconstruction showed age bias. Educational
      efforts should be instituted during the medical school to decrease ageism in
      students' treatment recommendations.

PMID- 11242583
TI  - Primary care residency graduates' reported training needs.
AB  - Primary care residency graduates were surveyed about their satisfaction with
      their training. The respondents desired more training in outpatient knowledge and
      procedures, psychosocial skills, and business skills.

PMID- 11242584
TI  - Evaluating clinical teachers: does the learning environment matter?
AB  - Teaching evaluations are an important part of promotion reviews. This study of
      the effect of learning environment on evaluations found ratings from students in
      ambulatory settings were higher than were those from inpatient settings.

PMID- 11242585
TI  - Teaching hypothesis-oriented thinking to medical students: the University of
      Florida's clinical investigation program.
AB  - Recent studies show alarming decreases in the proportions of physicians applying
      for federal resources and of graduating medical students who declare strong
      interest in pursuing careers as physician-scientists. To expose medical students
      in their formative years to hypothesis-driven experimental investigations in a
      clinical setting, the first-year curriculum at the University of Florida has
      involved students as both investigators and study subjects in patient-oriented
      research conducted in the General Clinical Research Center (GCRC). Each year a
      hypothesis-driven experiment is conceived by first-year medical students in the
      university's MD-PhD program. Later in the year, the protocol is implemented in
      the GCRC by the entire freshman class, whose members serve as volunteer study
      subjects or as investigators. The experimental data are analyzed by the MD-PhD
      students, who report their findings at national biomedical research meetings and
      submit a manuscript on their project to a peer-reviewed journal. The authors
      describe students' research projects over the first six years of this GCRC-based
      program. They also describe the responses of former students to a questionnaire
      about their perceptions of the value of the research program. Most respondents
      considered the GCRC research exercise to have been useful and relevant to their
      overall education, and many more declared a current interest in pursuing research
      careers compared with the number who had declared such interest as freshmen. The
      authors conclude that early integration of hands-on, patient-oriented research
      into the medical school curriculum is a positive educational experience for
      students, and may contribute to their ultimate pursuit of academic research
      careers.

PMID- 11242586
TI  - A teaching unit in primary care sports medicine for family medicine residents.
AB  - The authors describe their experience in setting up a sports medicine teaching
      unit within a family practice center of a teaching hospital. The unit's patient
      population more closely resembles that of a typical family practice than that of
      a traditional musculoskeletal teaching clinic (e.g., orthopedics, emergency
      room). The teaching program includes direct observation of residents performing
      history taking and physical examinations through one-way mirrors, close
      supervision for each case, and a sports therapist who educates patients and
      residents about home exercise programs when physiotherapy within private clinics
      is not necessary or affordable. At the end of each session 20-30 minutes are
      devoted to teaching specific physical examination skills. The authors describe
      how their clinic interacts with other services within the hospital and how
      certain obstacles they encountered when setting up the clinic might be avoided by
      others. They feel that this type of unit complements other existing programs in
      the family medicine department and provides an excellent learning experience for
      family medicine residents, who are likely to see a high proportion of patients
      with muskuloskeletal injuries in their practices.

PMID- 11242587
TI  - Residents' preparation for and ability to manage ethical conflicts in Korean
      residency programs.
AB  - The doctor-patient relationship in Korea has been deteriorating, and the numbers
      of malpractice suits and other medical disputes have been increasing annually for
      the past decade. Part of the problem may be physicians' lack of ethics education.
      The author and colleagues surveyed Korean residents from 14 university hospitals
      and found that most regularly experienced serious ethical dilemmas and had
      difficulty appropriately managing them. Few were familiar with medical law, and
      many resolved ethical conflicts either on their own or by talking with
      colleagues. Many did not follow guidelines for obtaining informed consent. Few
      had ethics committees or consultants available to them, and most did not discuss
      ethical dilemmas with attending physicians. The author describes the kinds of
      dilemmas faced by Korean residents and how they manage them, and he offers
      recommendations for improving ethics education and the ethics environment for
      Korean medical students and residents.

PMID- 11242589
TI  - Functional pleiotropy of an intramolecular triplex-forming fragment from the 3'
      UTR of the rat Pigr gene.
AB  - A microsatellite-containing 359-bp restriction fragment, isolated from the rat
      Pigr gene (murine polymeric immunoglobulin receptor gene) 3'-untranslated region
      (3'-UTR) and inserted into 3'-UTR or 3' flanking positions in transcription units
      of supercoiled plasmids, attenuates luciferase reporter gene expression in
      orientation- and position-dependent ways following transient transfection of
      human 293 cells. The same fragment stimulates orientation-dependent gene
      expression in a 5' flanking position. Plasmid linearization abrogates both
      orientation- and position-dependent responses. Cell-free translation reveals that
      5' and 3' flanking expression responses are proportional to increased and
      decreased luciferase mRNA levels, whereas 3'-UTR expression is associated with
      control mRNA levels. Hypersensitivity to nucleases S1 and P1, gel mobility
      differences between supercoiled plasmids carrying opposing microsatellite
      orientations, and anomalous melting profiles of this fragment are also observed.
      These results suggest that functional pleiotropy of this fragment depends on the
      DNA context of its purine-rich microsatellite strand and on DNA supercoiling.
      Intramolecular triplexes stabilized by supercoiling and secondary structures of
      purine repeat-rich mRNAs may also confer regulatory properties to similar genomic
      elements.

PMID- 11242590
TI  - Senescence-related changes in gene expression in muscle: similarities and
      differences between mice and men.
AB  - A microarray study of the effect of senescence in mice on gene expression in
      muscle has been published recently. The present analysis was done to evaluate the
      extent to which the age-related differences in gene expression in murine muscle
      are also evident in human muscle. RNA extracted from muscle of young (21-24 yr)
      and old men (66-77 yr) was studied both by serial analysis of gene expression
      (SAGE) and by oligonucleotide microarrays. SAGE tags were detected for 61 genes
      homologous to genes reported to be differentially expressed in young and old
      murine muscle. The microarray had probe sets for 70 homologous genes. For 17
      genes, there was evidence for a similar age-related change in expression in
      muscles of mice and men. For 32 other genes, there was evidence that the effect
      of age on the level of expression is not the same in mice and men. There was no
      evidence that older human muscle has increased expression of the stress response
      genes that are increased in old murine muscle.

PMID- 11242591
TI  - A quantitative trait locus influencing estrogen levels maps to a region
      homologous to human chromosome 20.
AB  - Estrogen, a steroid hormone, regulates reproduction and has been implicated in
      several diseases. We performed a genome-wide scan using multipoint linkage
      analysis implemented in a general pedigree-based variance component approach to
      identify genes with measurable effects on variation in estrogen levels in
      baboons. A microsatellite polymorphism, D20S171, located on human chromosome
      20q13.11, showed strong evidence of linkage with a LOD score of 3.06 (P =
      0.00009). This region contains several potential candidate genes including
      melanocortin 3 receptor (MC3R), cytochrome P-450 subfamily XXIV (CYP24), and
      breast carcinoma amplified sequence (BCAS1). This is the first evidence of a
      quantitative trait locus with a significant effect on estrogen.

PMID- 11242592
TI  - Amino acid translation program for full-length cDNA sequences with frameshift
      errors.
AB  - Here we present an amino acid translation program designed to suggest the
      position of experimental frameshift errors and predict amino acid sequences for
      full-length cDNA sequences having phred scores. Our program generates artificial
      insertions into artificial deletions from low-accuracy positions of the original
      sequence, thereby generating many candidate sequences. The validity of the most
      probable sequence (the likelihood that it represents the actual protein) is
      evaluated by using a score (V(a)) that is calculated in light of the Kozak
      consensus, preferred codon usage, and position of the initiation codon. To
      evaluate the software, we have used a database in which, out of 612 cDNA
      sequences, 524 (86%) carried 773 frameshift errors in the coding sequence. Our
      software detected and corrected 48% of the total frameshift errors in 62% of the
      total cDNA sequences with frameshift errors. The false positive rate of
      frameshift correction was 9%, and 91% of the suggested frameshifts were true.

PMID- 11242593
TI  - Long-term telemetric measurement of cardiovascular parameters in awake mice: a
      physiological genomics tool.
AB  - The recent miniaturization of implantable radiotelemetric devices offers the
      possibility of an accurate, reliable, and simple phenotyping tool for long-term,
      hands-off measurement of blood pressure in unrestrained, untethered mice;
      however, use has been limited because of high morbidity and mortality in all but
      larger-than-average mice. Also, because the device was developed for abdominal
      aorta implantation at the renal artery level, its use has not been feasible in
      studies where infrarenal blood flow is critical, i.e., in pregnant mice. We
      provide details of a very successful alternative approach for implanting
      radiotelemeters in mice, whereby thoracic aortic implantation of the pressure
      sensing catheter is combined with subcutaneous placement of the transmitter body
      along the right flank. We used female C57/BL6 (C57) or BPH/5 mice, a strain
      derived from the cross of inbred hypertensive and hypotensive mouse strains. We
      show that this is a reliable procedure for providing high-fidelity mean arterial
      pressure (MAP) and heart rate (HR) recordings for 50-60 days in mice weighing 22
      g on average but as small as 17 g. No morbidity or mortality was observed in
      either strain using this procedure. Importantly, neither strain fully recovered
      from anesthesia and surgery, as indicated by a return of normal circadian
      rhythms, until 5-7 days postsurgery. This was also reflected in significantly
      elevated baseline MAP and HR levels in both strains during this recovery period.
      Moreover, strain-related differences in relative increases in MAP during the
      first 5 days of recovery masked the significant elevation in BPH/5 baseline MAP
      (vs. C57) observed in fully recovered mice. This suggests that methods must allow
      at least 5-7 days recovery from surgery to provide accurate cardiovascular (CV)
      phenotyping in mice. Finally, we show that CV parameters can be monitored
      continuously before, during, and after pregnancy in mice using this alternative
      implantation approach. The device did not interfere with conception, gestation,
      delivery, or postnatal care of pups. These results demonstrate the feasibility of
      stress-free, long-term monitoring of CV parameters in pregnant or nonpregnant
      mice of typical size and offer exciting possibilities for application in CV
      functional genomic research.

PMID- 11242594
TI  - Identifying marker genes in transcription profiling data using a mixture of
      feature relevance experts.
AB  - Transcription profiling experiments permit the expression levels of many genes to
      be measured simultaneously. Given profiling data from two types of samples, genes
      that most distinguish the samples (marker genes) are good candidates for
      subsequent in-depth experimental studies and developing decision support systems
      for diagnosis, prognosis, and monitoring. This work proposes a mixture of feature
      relevance experts as a method for identifying marker genes and illustrates the
      idea using published data from samples labeled as acute lymphoblastic and myeloid
      leukemia (ALL, AML). A feature relevance expert implements an algorithm that
      calculates how well a gene distinguishes samples, reorders genes according to
      this relevance measure, and uses a supervised learning method [here, support
      vector machines (SVMs)] to determine the generalization performances of different
      nested gene subsets. The mixture of three feature relevance experts examined
      implement two existing and one novel feature relevance measures. For each expert,
      a gene subset consisting of the top 50 genes distinguished ALL from AML samples
      as completely as all 7,070 genes. The 125 genes at the union of the top 50s are
      plausible markers for a prototype decision support system. Chromosomal aberration
      and other data support the prediction that the three genes at the intersection of
      the top 50s, cystatin C, azurocidin, and adipsin, are good targets for
      investigating the basic biology of ALL/AML. The same data were employed to
      identify markers that distinguish samples based on their labels of T cell/B cell,
      peripheral blood/bone marrow, and male/female. Selenoprotein W may discriminate T
      cells from B cells. Results from analysis of transcription profiling data from
      tumor/nontumor colon adenocarcinoma samples support the general utility of the
      aforementioned approach. Theoretical issues such as choosing SVM kernels and
      their parameters, training and evaluating feature relevance experts, and the
      impact of potentially mislabeled samples on marker identification (feature
      selection) are discussed.

PMID- 11242595
TI  - Chronic myeloid disorders: Classification and treatment overview.
AB  - Chronic myeloid disorders (CMD) are collectively characterized by monoclonal
      myeloproliferation that involves multiple lineages, retains a variable degree of
      cellular maturation, and has the potential to undergo clonal evolution. However,
      monoclonal hematopoiesis is neither essential nor specific to CMD. Morphologic
      and cytogenetic characteristics allow a working classification of these disorders
      that is clinically useful. There are four major divisions: chronic myeloid
      leukemia (CML), which is easily identified by the presence of the Philadelphia
      chromosome (or its molecular equivalent); the myelodysplastic syndromes (MDS),
      which are characterized by trilineage dysplasia; chronic myeloproliferative
      diseases (CMPD), which include essential thrombocythemia, polycythemia vera, and
      agnogenic myeloid metaplasia (AMM); and atypical CMD, which includes chronic
      neutrophilic leukemia, chronic eosinophilic leukemia, mast cell disease, and
      myeloid processes that display overlapping features of MDS and CMPD (hybrid CMD).
      In CMPD, a diagnosis of polycythemia vera requires evidence of an erythropoietin
      independent increase in red blood cell mass; the diagnosis of both AMM and
      essential thrombocythemia requires the exclusion of reactive causes of bone
      marrow fibrosis and thrombocytosis, respectively. In addition, the Philadelphia
      chromosome, increased red blood cell mass, and dyserythropoiesis should also be
      absent. Semin Hematol 38(suppl 2):1-4.

PMID- 11242596
TI  - Physiology of myeloproliferation.
AB  - The current dogma about polycythemia vera (PV) is that one or more genetic
      mutations in a hematopoietic stem cell (HSC) cause abnormal proliferation and
      differentiation of the progeny of that stem cell. This model ignores two
      fundamental characteristics of biologic systems that must be considered if
      regulation is to be understood: first, at a molecular level, biochemical
      processes are intrinsically stochastic; and second, ontogeny and hematopoiesis
      are branching processes-with one cell dividing into two cells, and so on. Why is
      it important to add an understanding of the stochastic, branching nature of HSC
      function to a description of the genes and gene products only? Why not just say
      one understands the regulation of normal hematopoiesis, or PV, when all the genes
      and gene products actively transcribed have been identified? The answer is that
      within a branching, stochastic process, one mutation can cause more than one
      outcome (phenotype) in the future. There will be one or more related outcomes
      that will be highly likely and others that will be less likely. Although most
      patients will have similar phenotypes, some will differ, but not because they
      have different underlying mutations. Mathematics will probably play an
      increasingly important role in describing and analyzing the regulation that
      occurs as the genetic program of HSC is expressed within a clone over time. Semin
      Hematol 38(suppl 2):5-9.

PMID- 11242597
TI  - Pathogenetic mechanisms of polycythemia vera and congenital polycythemic
      disorders.
AB  - The absolute polycythemias--those with increased red blood cell mass--can be
      divided into two groups: primary, caused by acquired or inherited mutations
      leading to a "gain-of-function" abnormalities expressed within the erythroid
      progenitors; and secondary, due to circulating serum factors, typically
      erythropoietin, stimulating erythropoiesis. This overview concentrates on the
      molecular biology of polycythemia vera (PV) discussed in the context of other
      polycythemic disorders. Recent advances in the regulation of erythropoiesis, as
      they may relate to polycythemic states, are discussed as a background for those
      well-defined polycythemic states wherein the molecular defect has not yet been
      elucidated. A number of cellular abnormalities associated with PV, including the
      hyperresponsiveness of PV progenitors to many cytokines as well as decreased
      expression of the thrombopoietin receptor on platelets and increased expression
      of Bcl-xL, suggest that the PV defect alters a number of cellular functions and
      is not restricted to cytokine receptor signal transduction. The increasing number
      of recognized instances of familial incidence of PV suggests that in these
      families the predisposition for PV is inherited as a dominant trait, and that PV
      is acquired as a new mutation that leads to a clonal hematopoiesis and may be due
      to loss of heterozygosity. The existence of these families provides a unique
      opportunity for isolation of the mutations in the gene leading to PV. Semin
      Hemaol 38(suppl 2):10-20.

PMID- 11242598
TI  - Evaluation of diagnostic criteria in polycythemia vera.
AB  - There is no single diagnostic marker for the only known type of primary acquired
      erythrocytosis, polycythemia vera (PV). The Polycythemia Vera Study Group (PVSG)
      used a combination of major and minor diagnostic criteria. However, these
      guidelines have some limitations and in the presence of newer diagnostic tools,
      have been re-evaluated. The recommendations of the Radionuclide Panel of the
      International Council for Standardization Hematology based on surface area are
      recommended over red blood cell mass (RCM) mL/kg expressions. Absolute
      erythrocytosis can be assumed in males and females with packed cell volume (PCV)
      values greater than 0.60 and greater than 0.56, respectively. A satisfactory
      strategy of investigation for a secondary erythrocytosis must be used. Hypoxemia,
      as well as renal and hepatic pathology, must be excluded. In unexplained absolute
      erythrocytoses, pO(2)(50) values and serum erythropoietin (EPO) levels should be
      examined. The latter can be disappointing in the confirmation of a secondary
      erythrocytosis, but elevated values contraindicate a diagnosis of a primary
      erythrocytosis. Establishment of a clonal marrow population supports a diagnosis
      of PV. Thus an acquired karyotypic abnormality is a major criterion. Palpable
      splenomegaly remains an important diagnostic marker. Scanning techniques to
      demonstrate splenic enlargement should be used with caution. Allowance must be
      made for interobserver and intraobserver differences and variation in normal
      spleen size with age and size of the subject. Splenomegaly demonstrated in this
      way should be taken as a minor criterion. An increased neutrophil count (>10 x
      10(9)/L and >12.5 x 10(9)/L in smokers) is readily measurable and should replace
      total white blood cell count. The error in measurement of neutrophil alkaline
      phosphatase (NAP) score is large, making it an unsuitable diagnostic criterion.
      Neutrophil and platelet counts (>400 x 10(9)/L) should be taken as separate minor
      criteria. Endogenous erythroid colonies (EEC) grown from the peripheral blood
      have been used as a marker of PV, but it is an expensive technique that is not
      standardized and not totally specific for PV. Low serum EPO values found in the
      majority of patients with PV should hold a linked minor criterion position with
      EEC. Expert opinions should be obtained if bone marrow histology is to be used in
      the diagnosis of PV, but histology holds an important role in confirming the
      diagnosis. Semin Hematol 38(suppl 2):21-24.

PMID- 11242599
TI  - Current management in polycythemia vera.
AB  - Myeloproliferative diseases (MPD) include polycythemia vera (PV), essential
      thrombocythemia, agnogenic myeloid metaplasia, and chronic myelogenous leukemia.
      The focus of this report is on PV, which is characterized by an increase in red
      blood cells, granulocytes, and platelets. Complications associated with PV are an
      increased risk of thrombosis and abnormal bleeding. Phlebotomy to a hematocrit
      less than 45% is the mainstay of treatment for erythrocythemia, but may further
      increase the platelet count, necessitating the use of a platelet-lowering agent
      in conjunction with phlebotomy. Other treatment strategies include low-dose
      aspirin or other antithrombotic therapy and cytoreduction. Mounting evidence of
      the leukemogenicity and mutagenicity of radioactive phosphorus and alkylating
      agents, as administered using "conventional" regimens, has restricted the liberal
      use of these treatments. Three drugs have emerged as useful because of their
      efficacy in reducing the elevated platelet count: anagrelide, hydroxyurea (HU),
      and interferon alfa (IFN). It is clear that no single agent satisfies all the
      needs for cytoreduction that arise during the course of PV. Future protocols
      should be designed that draw on the large body of experience already gained with
      these drugs to transcend the limitations of single-agent therapy and to improve
      quality of life as well as survival. Semin Hematol 38(suppl 2):25-28.

PMID- 11242600
TI  - Environmental allergen avoidance: an overview.

PMID- 11242601
TI  - The biology of dust mites and the remediation of mite allergens in allergic
      disease.
AB  - In most temperate humid areas of the world, house dust mites are a major source
      of multiple allergens in house dust. Mite allergens sensitize and induce
      perennial rhinitis, asthma, or atopic dermatitis in a large portion of patients
      with allergic disease. There is convincing evidence that avoidance of mite
      allergen can effectively reduce allergic symptoms. Patients can be moved to a
      mite allergen-free environment, or mite and mite allergen abatement can be
      performed to reduce exposure in existing residences. Some knowledge of the
      biology of house dust mites is essential to understand the basis of the
      recommendations for reducing mites and mite allergens in homes and to appreciate
      the difficulty of eliminating house dust mites and mite allergens from homes.
      This article reviews key aspects of the biology of dust mites, the properties of
      mite allergens, recommendations for reducing mite and mite allergen
      concentrations in homes, and practical recommendations for treatment.

PMID- 11242602
TI  - The role and remediation of animal allergens in allergic diseases.
AB  - Animal allergens are common causes of both acute and chronic allergic disease.
      The most important animal allergens are derived from mammals, principally cats,
      dogs, rats, mice, horses, and cows, which secrete or excrete allergens into the
      environment. Allergic sensitization may occur at home or in the workplace. Cat
      and dog allergens commonly cause allergies in the home and affect the general
      population. Laboratory animal handlers often have allergic reactions to rats and
      mice. Cow dander allergy is usually caused by occupational exposure and occurs in
      farmers and farm workers. Horse allergy occurs among people who regularly handle
      horses, either professionally or for recreational purposes. Over the past 20
      years, the major animal allergens have been defined and characterized with regard
      to their molecular structure, immunogenicity, and environmental distribution. One
      remarkable finding has been the fact that most of the mammalian allergens that
      have thus far been cloned belong to a single family of proteins called the
      lipocalins. In addition to these molecular similarities, it has also been shown
      that most of the animal allergens are quite similar with regard to their
      aerodynamic properties. Although much is yet to be learned, progress is being
      made in our knowledge regarding the steps that may be necessary to control
      exposure to these allergens through environmental modifications in both homes and
      occupational settings. These measures include source control, air filtration
      devices, barrier devices, removal of carpeting and other reservoirs, and, in some
      cases, washing of the animal.

PMID- 11242603
TI  - Ecology and elimination of cockroaches and allergens in the home.
AB  - Cockroach infestations have been indicated as a major contributor to asthma
      throughout the world. Several studies have shown that large numbers of asthmatic
      patients are sensitized to cockroach allergens. Eliminating this pest from homes,
      schools, and public buildings involves a long-term commitment to a rational
      extermination process. This article covers the characteristics of the major
      cockroach species that invade homes, assesses the role of environmental exposure
      to cockroaches in asthma, and provides an intervention program for their
      extermination.

PMID- 11242605
TI  - How long can insulin therapy be avoided in the patient with type 2 diabetes
      mellitus by use of a combination of metformin and a sulfonylurea?
AB  - OBJECTIVE: To assess the effective longevity of combination double oral therapy
      before insulin or triple oral therapy is needed in patients with type 2 diabetes
      mellitus. METHODS: We retrospectively reviewed the outcomes of our first 100
      patients with type 2 diabetes who were successfully transferred from twice-daily
      mixed NPH and regular insulin to a combination of metformin and a sulfonylurea.
      RESULTS: Of the 100 study patients, 40 had well-controlled plasma glucose
      (glycosylated hemoglobin levels <8.0%) with use of metformin and a sulfonylurea.
      Good glycemic control was achieved with triple oral therapy (a sulfonylurea,
      metformin, and a thiazolidinedione) in 14 patients and with a sulfonylurea,
      metformin, and evening-administered mixed NPH and regular insulin in 7. In
      addition, plasma glucose was effectively controlled with twice-daily mixed NPH
      and regular insulin in conjunction with metformin or a thiazolidinedione (or
      both) in 22 patients and with twice-daily mixed NPH and regular insulin alone in
      17. The mean time (+/- standard error) from primary failure of sulfonylurea
      monotherapy to the time when a third hypoglycemic agent was needed was 7.9 +/-
      1.1 years (95% confidence interval, 5.7 to 10.1). CONCLUSION: When oral
      monotherapy fails (that is, glycosylated hemoglobin values exceed 8.0%) in
      patients with type 2 diabetes, combination therapy with a sulfonylurea and
      metformin is potentially effective in maintaining glycemic control and avoiding
      the addition of insulin or a thiazolidinedione for a mean duration of 7.9 years.

PMID- 11242604
TI  - The role and abatement of fungal allergens in allergic diseases.
AB  - Sensitivity to a variety of fungi is known to be a factor in allergic rhinitis
      and asthma. In this review methods for measuring exposure to fungi in the indoor
      environment are evaluated. A variety of markers for the presence of fungi are
      also described in addition to their known relationship to either toxic or adverse
      immunologic effects. Key studies documenting the clinical effects of different
      types of fungi are also reviewed, as well as a description of abatement methods
      that either have been successful or need further investigation. Although many
      studies have shown an association between exposure to fungi and allergic disease,
      in many cases a direct cause-and-effect relationship has not been established.
      Improved knowledge of the epidemiology and mechanisms behind fungal-induced human
      disease will hopefully establish this causal link and suggest methods for
      reducing morbidity.

PMID- 11242606
TI  - Osteoporosis and low bone mass in premenopausal and perimenopausal women.
AB  - OBJECTIVE: To characterize the historical, clinical, and biochemical features of
      111 young women (age, <55 years) referred for evaluation of osteoporosis or low
      bone mass. METHODS: Women with a bone mineral density T score < or = -2.0 (N =
      111) at one or more anatomic sites (by dual-energy x-ray absorptiometry) were
      assessed relative to anthropomorphic and biochemical characteristics and risk
      factors for osteoporosis. RESULTS: Of 111 women with low bone mass or
      osteoporosis, 73 (66%) had identifiable causes of bone loss, of which estrogen
      deficiency (menopause, premenopausal estrogen deficiency) and conditions
      associated with estrogen deficiency (anorexia nervosa, cancer chemotherapy) were
      the most common. Prolonged use of glucocorticoids was the most common secondary
      cause of osteoporosis. Of 38 women with no identifiable cause of bone loss, 21
      were premenopausal (mean age, 38 +/- 10 years [standard deviation]) and 17 were
      perimenopausal (mean age, 50 +/- 3 years). The mean lumbar spine T score was 
      2.18 +/- 1.0 in the premenopausal and -2.51 +/- 0.6 in the perimenopausal women.
      Nontraumatic fractures were reported by 42% of the premenopausal women and 18% of
      the perimenopausal women. A family history of osteoporosis was reported by 71% of
      the premenopausal and 47% of the perimenopausal women. CONCLUSION: Most young
      women with osteoporosis or low bone mass had estrogen deficiency or another
      secondary cause of premature bone loss (or both). A subset of premenopausal and
      perimenopausal women, however, had no identifiable cause of bone loss. The strong
      family history of osteoporosis, especially in the premenopausal women, provides
      further support for current theories of a genetic predisposition to osteoporosis.

PMID- 11242607
TI  - Troglitazone add-on therapy to a combination of sulfonylureas plus metformin
      achieved and sustained effective diabetes control.
AB  - OBJECTIVE: To elucidate the effect of triple combination oral agent therapy on
      type 2 diabetes. METHODS: We performed a prospective longitudinal study on 40
      patients with type 2 diabetes who had failed to achieve a glycosylated hemoglobin
      (HbA1c) of < or = 8.0% despite optimal therapy with a combination of
      sulfonylureas plus metformin. Troglitazone was added and then titrated, with the
      intent to achieve at least a 1% reduction in HbA1c within 3 months. Responders
      were reassessed at 6 and 12 months. Nonresponders were reassessed at 6 months; in
      the absence of a significant HbA1c response, participation in the study was
      discontinued. RESULTS: Of the 40 study subjects, 25 were responders, 10 were
      nonresponders, and 5 were withdrawn from the study before completion of 3 months
      of therapy because of side effects. The 25 responders had a mean baseline HbA1c
      of 9.9%, which decreased significantly to 7.8% after 3 months of troglitazone
      therapy and to 7.4% at 6 months and at 12 months. In addition, the fasting blood
      glucose (FBG) in the responders decreased significantly from 168 mg/dL at
      baseline to 118 mg/dL at 6 months, which was sustained at 121 mg/dL at 12 months.
      In the responder group, a mean HbA1c < or = 8% was achieved in 68% at 6 months
      and sustained in 65% after 1 year. Furthermore, 40% of responders achieved a mean
      HbA1c < or = 7.0% at 6 months, and 39% sustained this degree of control at 12
      months. The 10 nonresponders showed no significant change in HbA1c or FBG during
      the 6 months of troglitazone therapy. No difference existed in the mean baseline
      FBG, HbA1c, or C peptide level between the two groups. Responders, however, had a
      significantly lower mean body mass index (BMI) (31 kg/m2) than did nonresponders
      (37 kg/m2). Although responders were older than nonresponders (mean age, 65 years
      versus 55 years), no significant difference was noted in duration of diabetes
      (11.6 years versus 8.7 years). Multivariate analysis showed that male gender and
      BMI were the strongest predictors of a response to troglitazone add-on therapy to
      the prior combination of sulfonylureas plus metformin. CONCLUSION: This study
      showed that oral therapy with troglitazone added to sulfonylureas plus metformin
      achieved and sustained a significant improvement in control of diabetes in 71% of
      patients who had failed to achieve HbA1c < or = 8% with dual oral agent therapy.
      The positive response was evident within 3 months, reached maximum by 6 months,
      and was sustained to 12 months of therapy. Therefore, patients who fail to
      achieve HbA1c < or = 8% with sulfonylureas plus metformin should have at least 3
      months of troglitazone add-on therapy before advancing to traditional insulin
      treatment.

PMID- 11242608
TI  - Effect of an inhaled glucocorticoid, flunisolide, on bone mineral density: a 2
      year prospective, controlled trial.
AB  - OBJECTIVE: To determine the long-term effect of an inhaled glucocorticoid,
      flunisolide, on bone mineral density in a prospective, controlled study. METHODS:
      Patients with asthma treated with inhaled glucocorticoids, but not requiring
      other types of glucocorticoid treatment, were recruited as study patients (N =
      11). All study patients were treated with inhaled flunisolide, 500 mg twice a day
      for a 2-year period, for consistency. Patients with asthma not requiring any type
      of glucocorticoid treatment were recruited as control subjects (N = 18). All
      patients were between the ages of 30 and 50 years, and all female patients were
      premenopausal. Measurements of bone mineral density, serum bone-specific alkaline
      phosphatase, serum osteocalcin, 24-hour urine hydroxyproline-to-creatinine ratio,
      forced expiratory volume in 1 second/forced vital capacity, and forced expiratory
      flow, midexpiratory phase were obtained at baseline and repeated in 1 year and
      again in 2 years. RESULTS: No statistically significant changes were noted in
      bone mineral density measured at the lumbar spine, femoral neck, Ward's triangle,
      or femoral trochanter in the users of inhaled flunisolide in comparison with the
      control subjects at 1 year or at 2 years, with one exception. The percentage
      change from baseline of bone mineral density measured at the femoral trochanter
      at 1 year was greater in the inhaled flunisolide users than in the control group,
      3.1% versus -0.8%, respectively (P = 0.01). No statistically significant changes
      were found in markers of bone turnover or measures of asthma severity.
      CONCLUSION: Inhaled flunisolide, administered in standard doses, had no
      deleterious effect on bone mineral density or on biochemical markers of bone
      turnover after a 2-year period.

PMID- 11242609
TI  - Amyloid goiter: report of two cases and review of the literature.
AB  - OBJECTIVE: To describe two recent cases of amyloid goiter that occurred in two
      patients with a history of diffuse enlargement of the thyroid gland, progressing
      over several years' time. METHODS: We reviewed the medical histories as well as
      the histologic, immunohistochemical, and electron microscopic findings in these
      patients. RESULTS: Assessment of the clinical records of a 59-year-old man and a
      64-year-old woman revealed histories that included chronic psoriasiform arthritis
      and asthma in conjunction with chronic obstructive pneumonia and bronchiectasis.
      In both cases, total thyroidectomy was performed. On histologic examination of
      both thyroid glands, the appearance was characterized by moderate to severe
      distortion of the normal thyroid architecture by amyloid in a perifollicular
      distribution and focally abundant interfollicular adipose tissue. In both cases,
      the amyloid stained intensely positive with Congo red, which bleached after
      treatment with potassium permanganate. Immunohistochemical staining patterns were
      consistent with AA amyloid, and electron microscopy showed nonbranching 9-nm
      fibrils consistent with amyloid. CONCLUSION: The diagnosis of amyloid goiter
      should be suspected in patients with a diffusely enlarging thyroid gland and an
      appropriate clinical history.

PMID- 11242610
TI  - Nephrogenic diabetes insipidus persisting 57 months after cessation of lithium
      carbonate therapy: report of a case and review of the literature.
AB  - OBJECTIVE: To illuminate the natural history of prolonged nephrogenic diabetes
      insipidus after discontinuation of lithium carbonate treatment and to assess the
      response to therapy with desmopressin acetate and triamterene
      hydrochlorothiazide. METHODS: We analyzed sequential determinations of serum and
      urine osmolality, plasma arginine vasopressin, serum sodium, blood urea nitrogen,
      calcium, ionized calcium, parathyroid hormone, and 24-hour urine volume during a
      period of 57 months in a 67-year-old woman. RESULTS: Our patient experienced
      persistent polyuria in conjunction with having repeated serum osmolalities
      between 300 and 323 mOsm/kg and urine osmolalities between 130 and 208 mOsm/kg.
      Concomitant plasma arginine vasopressin levels were as high as 12.0 pg/mL,
      consistent with the diagnosis of nephrogenic diabetes insipidus. Administration
      of triamterene-hydrochlorothiazide reduced 24-hour urine volume and serum
      osmolality while increasing urine osmolality. Desmopressin acetate exhibited no
      effect. CONCLUSION: In this report, we describe the eighth documented case of
      persistent nephrogenic diabetes insipidus, lasting 57 months after cessation of
      lithium therapy, and demonstrate a palliative effect of triamterene
      hydrochlorothiazide.

PMID- 11242612
TI  - Ophthalmologic examinations in patients with diabetes: is once a year too often?

PMID- 11242611
TI  - Leukocytoclastic vasculitis: a rare manifestation of propylthiouracil allergy.
AB  - OBJECTIVE: To report a case of leukocytoclastic vasculitis as a manifestation of
      propylthiouracil allergy. METHODS: We present the history, findings on physical
      examination, and results of laboratory evaluation in a 25-year-old woman.
      Associated reports from the literature are reviewed. RESULTS: The patient, with a
      history of Graves' disease, was referred for evaluation of a purpuric rash on the
      pinnas and buttocks bilaterally. Findings included exophthalmos and bilateral
      goiter with neck bruits. She was biochemically hyperthyroid. Biopsy of the skin
      lesions revealed leukocytoclastic vasculitis. Propylthiouracil therapy was
      discontinued, and prednisone was prescribed. Treatment with radioactive iodine
      resulted in appreciably diminished skin lesions and reduction in the size of the
      thyroid gland, but thyroxine and triiodothyronine levels increased.
      Administration of a second, higher dose of radioactive iodine with concomitant
      lithium carbonate resulted in clinical and biochemical improvement. Six months
      after initial assessment, the rash had resolved, and the patient's free thyroxine
      value had normalized, although the thyrotropin level was still suppressed.
      CONCLUSION: Leukocytoclastic vasculitis, although rarely seen as a manifestation
      of propylthiouracil allergy, has been reported in the medical literature and
      should be considered in the differential diagnosis of patients with a vasculitic
      rash. Treatment consists of discontinuation of the offending medication and
      administration of a corticosteroid and, occasionally, cyclophosphamide or
      plasmapheresis.

PMID- 11242613
TI  - Is avoiding insulin therapy an achievable and worthwhile goal?

PMID- 11242614
TI  - "Does she or doesn't she...have osteoporosis?" The use and abuse of bone
      densitometry.

PMID- 11242615
TI  - Effectiveness of combination therapy with three orally administered antidiabetic
      drugs.

PMID- 11242616
TI  - Stapled haemorrhoidectomy--the evidence for and the facts against.

PMID- 11242617
TI  - A prospective evaluation of surgeon performed sonography as a screening test in
      blunt abdominal trauma.
AB  - INTRODUCTION: Sonography has found a role in the evaluation of patients with
      abdominal injury. However, the accuracy of sonography as performed by non
      radiologists remains controversial. This study aims to determine the accuracy of
      focused abdominal sonography for trauma when performed by surgeons. MATERIALS AND
      METHOD: Over a 1-year period, 48 patients with abdominal injury were initially
      evaluated for free intraperitoneal fluid by sonography. These tests were
      performed by 2 surgeons who had received instructions and performed a minimum of
      30 examinations. Sonographic findings were then compared with other diagnostic
      modalities including computed tomography (CT) scan, diagnostic peritoneal lavage
      and exploratory laparotomy. RESULTS: The sensitivity, specificity, positive
      predictive value, negative predictive value and accuracy for sonography were
      found to be 0.86, 0.92, 0.89, 0.90 and 0.89, respectively. Although not
      specifically sought for, 2 cases of solid organ injury and 1 haemothorax, which
      were missed in initial examinations and X-rays, were detected on sonography.
      CONCLUSION: In conclusion, our initial experience suggests that local surgeons
      can perform a focused sonographic examination for trauma with acceptable
      accuracy. Although sonography lacks the sensitivity of diagnostic peritoneal
      lavage and the accuracy of CT scan, the diagnostic algorithm for abdominal trauma
      should include sonography as a screening test.

PMID- 11242618
TI  - Effects of a pulmonary rehabilitation programme on physiologic and psychosocial
      outcomes in patients with chronic respiratory disorders.
AB  - INTRODUCTION: The purpose of this prospective study is to determine the effects
      of a pulmonary rehabilitation programme (PRP) conducted at our centre for
      patients with chronic lung disease. MATERIALS AND METHODS: Thirty-four patients
      (27 men and 7 women, mean age 67.7 years) with predominantly moderate-to-severe
      chronic obstructive pulmonary disease (31 patients), bronchiectasis (2 patients)
      and interstitial lung disease (1 patient) completed a 6-week outpatient PRP that
      included education, physical and respiratory care instruction and supervised
      exercise training. Outcome assessment was performed at baseline, on completion of
      PRP and 3 months after PRP. Physiologic measures included pulmonary function,
      incremental exercise and 6-minute walk tests (6MWTs). Disease-specific quality of
      life was assessed using the Chronic Respiratory Disease Questionnaire (CRDQ).
      RESULTS: There was no significant change in resting spirometry or lung volumes
      after PRP. Maximal oxygen uptake and work-rate improved significantly after PRP
      by 132.4 mL kg-1 min-1 and 10.7 W, respectively. 6MWT distance improved
      significantly by a mean of 67.3 m (P < 0.0001). Maximum Borg dyspnoea scores
      decreased significantly by 1.2 +/- 0.5 (P < 0.038). All domains of the CRDQ
      completed by a sub-group of patients improved significantly and the total scores
      increased by a mean of 21.7 points at the end of the PRP. The improvements gained
      in maximal exercise capacity immediately following PRP were maintained in 17
      patients who returned for repeat assessment 3 months after PRP. CONCLUSION:
      Patients who completed a comprehensive PRP at our centre showed significant
      increase in functional capacity, reduction of exertional dyspnoea and improvement
      in health status.

PMID- 11242619
TI  - Antibiotic sensitivity of Propionibacterium acnes isolates from patients with
      acne vulgaris in a tertiary dermatological referral centre in Singapore.
AB  - OBJECTIVES: To study the minimum inhibitory concentrations (MICs) of
      Propionibacterium acnes (P. acnes) isolates to selected antibiotics from patients
      with acne vulgaris in Singapore and determine if resistance increases with
      prolonged use of antibiotics. DESIGN: A single-centre prospective study. SETTING:
      Tertiary dermatological referral centre in Singapore. PATIENTS: One hundred and
      fifty patients with acne vulgaris seen at the National Skin Centre. RESULTS: In
      patients who had never been on antibiotics, there were no resistant isolates of
      P. acnes. In patients who had been on short-term antibiotics (between 6 to 18
      weeks), there were 2 resistant strains among the 34 isolates (6.25%); in patients
      who had been on antibiotics for longer periods, there were 11 resistant strains
      among the 51 isolates (21.6%). The differences in the rates of isolation of
      resistant strains between patients who had not been on antibiotics to those that
      had been on long-term antibiotics were statistically significant (P = 0.015).
      There was also a significant difference in isolation of resistant strains from
      those on short-term antibiotics compared to those who had been on long-term
      antibiotics (P = 0.036). Resistance to erythromycin was most commonly
      encountered. Most of the erythromycin-resistant strains also showed cross
      resistance to clindamycin. The average MICs to antibiotics such as minocycline,
      erythromycin and clindamycin in those on long-term antibiotics were significantly
      higher when compared to patients who had not been on antibiotics. CONCLUSIONS:
      Antibiotic resistance in P. acnes isolates in Singapore follows similar patterns
      to studies conducted in Europe. Resistance to erythromycin was most commonly
      seen, and this is associated with cross-resistance to clindamycin. Among the
      tetracycline group of drugs, the average MICs to tetracycline was higher than
      that for doxycycline, which in turn was higher than that for minocycline.
      Antibiotic resistance can occur with short-term antibiotic courses, and the rate
      of resistance increases as the duration of antibiotic consumption increases.

PMID- 11242620
TI  - The use of vigabatrin in infantile spasms in Asian children.
AB  - BACKGROUND: The use of adrenocorticotrophic hormone (ACTH) and prednisolone in
      the management of infantile spasms has been well established, but is associated
      with significant morbidity and cannot be used as long-term medication. Since the
      introduction of vigabatrin, results have been promising with suggestions
      currently that it should be used as first-line management of infantile spasms.
      AIM: The aim of this study was to establish the efficacy, tolerability and
      problems associated with the use of vigabatrin, in Asian children with infantile
      spasms. MATERIALS AND METHODS: Eighteen local Asian patients with infantile
      spasms were given vigabatrin, in 8 as first-line monotherapy and in 10 patients
      as add-on therapy to pre-existing anti-convulsants. RESULTS: Thirty-nine per cent
      (7/18) showed 100% suppression of seizures at 2 weeks and 50% (9/18) showing
      complete suppression of seizures at 4 weeks after starting therapy. There was
      however, a high relapse rate (56%) in complete responders within the first 6
      months of therapy. This was probably due to a lower maintenance dose in the
      patients, as those who relapsed were on an average dose of 59 mg/kg/day at the
      time of relapse and responded to a stepped up dose of 83 mg/kg/day. Vigabatrin
      was well tolerated and only 2 patients developed somnolence and irritability.
      CONCLUSION: A dose of at least 70 mg/kg/day may be necessary to achieve adequate
      control and yet avoid the common adverse affects of vigabatrin.

PMID- 11242621
TI  - Clinical utility of polymerase chain reaction in the detection of Mycobacterium
      tuberculosis in different types of cutaneous tuberculosis and tuberculids.
AB  - INTRODUCTION: The role of polymerase chain reaction (PCR) in the diagnosis of
      cutaneous tuberculosis in clinical practice has not been defined as no PCR assay
      has been tested in a large-scale clinical study. The objective of this study was
      to test the clinical utility of a PCR assay in the diagnosis of different types
      of cutaneous tuberculosis and tuberculids. MATERIALS AND METHODS: Analysis of
      archival biopsy specimens by a nested PCR assay targeting IS6110 of Mycobacterium
      tuberculosis (M. tb) DNA was performed in a tertiary-care skin hospital in
      Singapore. PCR results were compared with cultures and concordance with final
      diagnosis. PATIENTS AND SPECIMENS: One hundred and nineteen skin biopsies from
      105 patients comprising 58 cases of confirmed or highly probable cutaneous
      tuberculosis, ranging from multibacillary infections to paucibacillary forms and
      47 cases of possible tuberculids were analysed. Twenty-four subjects with non
      tuberculous granulomas and normal skin controls were included. RESULTS: In 14
      immunocompromised patients with multibacillary mycobacterial infections (AFB+ on
      biopsy), PCR was positive in 9 patients. Correlating PCR results with the final
      diagnosis, the PCR technique was 100% sensitive and specific in this group. In
      paucibacillary tuberculosis, PCR positivity rates were 55% for tuberculosis
      verrucosa cutis (38 cases) and 60% for lupus vulgaris (5 cases). When confirmed
      cases of tuberculosis were considered, the overall sensitivity was 73%. In 26
      cases of erythema induratum, PCR was positive in 54% and correlated with a
      documented response to anti-tuberculous treatment in 80%. CONCLUSIONS: The use of
      PCR in the routine diagnostic panel for cutaneous tuberculosis should take into
      consideration the differential sensitivities for different clinical types. In the
      setting of an immunocompromised patient with AFB+ lesions, PCR has a definite
      role in rapid diagnosis and in differentiating atypical mycobacterial infection
      from tuberculosis. Where paucibacillary tuberculosis is suspected, clinical
      decision should not be based on PCR results alone. In erythema induratum, we
      found some correlation between PCR results and response to anti-tuberculous
      therapy.

PMID- 11242622
TI  - A retrospective study of melanocytic naevi at the National Skin Centre.
AB  - INTRODUCTION: A retrospective study of melanocytic naevi was undertaken to assess
      the degree of clinico-pathological correlation and incidence of histological
      atypia. MATERIALS AND METHODS: The case records from January to March 1996 of all
      patients with histologically diagnosed melanocytic naevi at the National Skin
      Centre were analysed. RESULTS: Of the 240 lesions removed from 167 patients, the
      majority being women (111/167 patients), it was found that 55% (132/240) were
      correctly diagnosed. Fourteen per cent were mistaken for non-melanocytic lesions,
      namely skin tag, neurofibroma, syringoma cylindroma, epidermal naevus, naevus
      sebaceous and basal cell carcinoma. Most of the lesions were located on the
      cheeks and eyelids. Junctional naevi, followed by compound naevi were often
      missed. Histological dysplasia were seen in 7 naevi; 6 compound and 1 congenital
      naevi. There was a lack of clinico-pathological concordance in dysplastic naevi.
      CONCLUSIONS: The clinico-pathological concordance of melanocytic naevi was high,
      with low incidence of atypia on histology.

PMID- 11242623
TI  - The views of mental health professionals towards psychotherapy--a Singapore
      survey.
AB  - OBJECTIVE: There is no published data on how mental health professionals (MHPs)
      in developing Asian countries view psychotherapy. Since practitioners of
      psychotherapy may come from both medical and non-medical (e.g. clinical
      psychology, social work, counselling) backgrounds, differences between the 2
      groups may have practical significance. The aims of this study were to examine
      the views of MHPs in Singapore towards psychotherapy and to determine if there
      are differences in the views of psychiatric versus non-psychiatric professionals.
      MATERIALS AND METHODS: Fourteen statements covering various aspects of
      psychotherapy were given to a sizeable sample of MHPs consisting 70 psychiatric
      and 70 non-psychiatric professionals. Their responses on a 5-point Likert scale
      were analysed using appropriate statistical tests to determine similarities and
      differences of the 2 groups. RESULTS: Despite essential agreement in the
      definition of psychotherapy, significant differences exist between the 2 groups
      in the following areas: (1) distinction between psychotherapy and counselling,
      (2) use of medication during psychotherapy, (3) whether the duration of
      psychotherapy should be determined at the start of treatment, and (4) whether
      negative effects of psychotherapy exist. There was consensus that psychotherapy
      should be stopped when psychotic symptoms emerge in the course of such treatment.
      CONCLUSIONS: Significant similarities and differences exist in the views of
      psychiatrists and the other MHPs. The practical implications of these findings
      for psychotherapy training and the provision of psychotherapy services in Asia
      are discussed. Literature is reviewed to address the issues raised.

PMID- 11242624
TI  - Liver transplantation in a child with severe hypercholesterolaemia in Alagille
      syndrome.
AB  - INTRODUCTION: Liver transplantation is a curative treatment modality in children
      with end stage liver disease in Alagille syndrome. CLINICAL PICTURE: We report a
      3-year-old child with this condition who had severe hypercholesterolaemia,
      pruritus and extensive xanthomatosis. TREATMENT: Liver transplantation was
      performed in this patient. OUTCOME: He recovered well with normalisation of his
      lipid profile. This procedure also resulted in resolution of the disfiguring
      xanthomatosis.

PMID- 11242625
TI  - Melioidosis splenic abscess--an unusual presentation as osteomyelitis of rib.
AB  - INTRODUCTION: We report an unusual case of splenic melioidosis abscess presenting
      as osteomyelitis. CLINICAL PICTURE: A 74-year-old nondiabetic gentleman presents
      with a non-healing left chest wall abscess from osteomyelitis. TREATMENT: He
      underwent rib resection and the infection was found to involve the underlying
      pleura, lung, adjacent stomach, liver and diaphragm with a splenic abscess.
      Splenectomy was performed. Histology showed suppurative granulomas and cultures
      grew Burkholderia pseudomallei. OUTCOME: The patient recovered well with
      antibiotics. CONCLUSION: Melioidosis should not be forgotten as a cause of
      chronic suppurative infections in our endemic population.

PMID- 11242626
TI  - Galeazzi-equivalent fracture in children associated with tendon entrapment-
      report of two cases.
AB  - INTRODUCTION: This is a report of 2 consecutive cases of the Galeazzi-equivalent
      fracture in children. CLINICAL PICTURE: In both cases, the mechanism of injury
      was falls onto the outstretched hand. Radiographs showed fracture of the radius
      with separation of the distal ulnar physis. TREATMENT: Initial treatment by
      closed manipulation failed; hence, open reduction and internal fixation was
      required. The cause of failure of closed manipulation in both cases was
      interposition of soft tissue into the ulnar fracture site. OUTCOME: Both cases
      showed good functional outcome after open reduction and internal fixation.
      CONCLUSION: Recognition of this form of injury is necessary to ensure proper
      treatment is undertaken to prevent the complications of inadequate reduction and
      growth retardation.

PMID- 11242627
TI  - Case report: acute tumour lysis syndrome.
AB  - INTRODUCTION: Acute tumour lysis syndrome (ATLS) is a potentially lethal but
      preventable complication of oncological treatment. CLINICAL PICTURE: We report a
      case of a patient with Burkitt's leukaemia who developed ATLS after treatment
      with chemotherapy. TREATMENT: Standard preventive measures using aggressive
      hydration, urine alkalinisation and uricosuric agents were instituted before
      chemotherapy. OUTCOME: However in spite of adequate measures, the patient
      succumbed to the sequelae of ATLS. CONCLUSIONS: It is therefore important to
      identify patients who are at a high risk of developing ATLS so that additional
      measures can be taken to prevent it from occurring.

PMID- 11242629
TI  - Case report: catheter-related epidural abscess.
AB  - INTRODUCTION: Catheter-related spinal epidural abscesses are rare but increasing
      in incidence. CLINICAL PICTURE: An elderly gentleman received 4 days of
      continuous epidural analgesia following multiple traumatic rib fractures. Five
      days subsequently, he developed an extensive epidural abscess accompanied by
      backache, lower limb weakness, fever, leukocytosis and Staphylococcal
      bacteraemia. TREATMENT: He received appropriate intravenous antibiotics and
      underwent an emergent decompressive laminectomy. OUTCOME: A good outcome was
      achieved because of prompt diagnosis, appropriate intravenous antibiotics and
      timely surgical intervention. CONCLUSIONS: It is important to be vigilant and
      continue to maintain good clinical practice and a high index of suspicion for
      this procedural-related complication.

PMID- 11242628
TI  - A case of alpha-fetoprotein-producing gastric cancer.
AB  - INTRODUCTION: A case of alpha-fetoprotein (AFP)-producing gastric cancer is
      described in a 57-year-old Chinese woman. CLINICAL PICTURE: She presented with
      bleeding tendency and bone pain, and was found to have haematological evidence of
      disseminated intravascular coagulation and spinal metastasis. Her tumour markers,
      including AFP, Ca 19-9 and carcinoembryonic antigen (CEA) were elevated. In view
      of the elevated tumour markers, there was an exhaustive search for a primary
      lesion in the gastrointestinal tract, liver and ovaries. There was no
      radiological evidence to suggest any lesion in the chest, liver or pelvis. Lectin
      affinity electrophoresis of the AFP showed AFP-L2 and AFP-L3 bands, which are
      suggestive of a non-hepatoma malignancy. MANAGEMENT: Gastroscopy showed a gastric
      ulcer and she developed bleeding after the gastric biopsy which required urgent
      surgery. Intraoperatively she was found to have carcinomatous peritone and a
      malignant ulcer in the greater curve of the stomach. Histology confirmed a
      linitis plastica like adenocarcinoma which stains for AFP. OUTCOME: She died from
      multi-organ failure 3 days after surgery. CONCLUSION: AFP-producing
      adenocarcinoma of the stomach is not uncommon. Lectin affinity electrophoresis of
      AFP is helpful in the differentiation between hepatoma and non-hepatoma
      malignancies.

PMID- 11242631
TI  - 46, XY female--a case report.
AB  - INTRODUCTION: We examine a presumptive case of complete androgen insensitivity
      syndrome (CAIS) with certain unusual features. CLINICAL PICTURE: A woman with
      early onset osteoporosis gave a history of primary amenorrhoea and surgery for
      intraabdominal gonads. She subsequently defaulted follow-up and hormone
      replacement therapy. Endocrinological evaluation revealed hypergonadotrophic
      hypogonadism associated with a 46,XY karyotype. TREATMENT: Therapy included
      reinforcement of the female phenotype and oestrogen replacement. OUTCOME: There
      was gradual development of her secondary sexual characteristics and improvement
      in her bone mineral density. CONCLUSION: Patients with CAIS need proper
      counselling and education according to their psychosexual make-up and
      sociocultural factors. The importance of long-term oestrogen replacement in a
      young subject post-gonadectomy cannot be overemphasized as illustrated in our
      case.

PMID- 11242630
TI  - A case report of primary hyperparathyroidism with severe bony involvement and
      nephrolithiasis.
AB  - INTRODUCTION: Although the majority of patients with primary hyperparathyroidism
      have a relatively asymptomatic benign disorder, there are patients who have a
      more aggressive disorder. CLINICAL PICTURE: We report a case of primary
      hyperparathyroidism presenting during pregnancy complicated by antepartum
      haemorrhage and severe prematurity. The diagnosis was made postpartum, when her
      problems rapidly progressed to result in severe neuromuscular weakness, bilateral
      pathological hip fractures as well as nephrolithiasis. TREATMENT: Surgical
      parathyroidectomy was performed. The underlying lesion was a large solitary
      parathyroid adenoma with cystic elements. CONCLUSION: Primary hyperparathyroidism
      is not an innocuous disease and can result in severe morbidity if left untreated.

PMID- 11242632
TI  - [Molecule targeted therapy for hematological malignancies].
AB  - Over the past 20 years, there has been a marked increase in our knowledge of the
      molecular mechanisms of human hematological malignancies. The development of
      mechanism-based therapy is expected to extend the frontiers of chemotherapy. All
      trans retinoic acid (ATRA) therapy for acute promyelocytic leukemia (APL),
      initially established as differentiation therapy, has been recognized to target
      PML-RAR alpha protein, an APL-specific chimeric transcriptional factor, and to
      modulate the function. Recently, encouraging results have emerged in the
      treatment of chronic myeloid leukemia with a tyrosine-kinase inhibitor. In
      addition to the oncoprotein-targeted therapy, the clinical effectiveness of
      humanized monoclonal antibodies to differentiation antigens has been recognized.
      Molecule-targeted therapy is reviewed herein.

PMID- 11242633
TI  - [Current status on the epidemiological studies of cancer of the major organs:
      introduction].

PMID- 11242635
TI  - [Risk factors of stomach cancer].
AB  - The risk factors for stomach cancer are reviewed. A family history of stomach
      cancer, smoking habit, highly salted foods and Helicobacter pylori are risk
      factors, while fresh vegetables, fruits and green vegetables are preventive ones.
      Stomach cancer may arise mainly from moderately but not severely atrophic gastric
      mucosa, where atrophic change is ongoing. New strategies for primary and
      secondary prevention of stomach cancer should be built utilizing these recent
      findings.

PMID- 11242634
TI  - [Time-trends in cancer incidence and mortality in Japan].
AB  - The cancer incidence and mortality in Japan are described herein. The total
      number of deaths from all malignant neoplasms in 1998 was 284,000, corresponding
      to 30.3% of the total number of deaths among Japanese. Lung was the leading site
      of cancer deaths (17.9%), followed by the stomach (17.9%), large bowel (12.1%),
      liver (11.8%), pancreas (6.2%), gallbladder and extrahepatic biliary tract
      (5.2%), lymphatic tissue (3.7%), esophagus (3.4%), breast (3.1%), prostate
      (2.4%), leukemia (2.3%) and uterus (1.8%). The stomach was the leading site of
      cancer deaths until 1997, but was replaced by the lungs in 1998. The age
      standardized mortality rates (1975-1998) have increased gradually for males, but
      decreased slightly for females. The rates have decreased remarkably for the
      stomach and uterus, while increasing for the lungs, large bowel, female breast,
      gallbladder and extrahepatic biliary tract, pancreas, and others. The total
      incidence for all cancers in Japan was estimated to be 454,000 in 1995. The
      stomach was the leading cancer site (22.2%), followed by the large bowel (17.7%),
      lung (11.6%), liver (7.8%), breast (6.6%), pancreas (3.7%), gallbladder and
      extrahepatic biliary tract (3.4%), lymphatic tissue (3.1%) and uterus (2.9%). The
      age-standardized incidence rates for all sites (1975-1995) have increased
      gradually for males, while remaining constant for females after a slight increase
      in the late 1970s. The incidence rates have decreased for the stomach and uterus,
      but increased for the large bowel, female breast, lung, liver, gallbladder and
      extrahepatic biliary tract, pancreas, prostate and others. The increase in the
      incidence rate was prominent for the large bowel, female breast and prostate.

PMID- 11242636
TI  - [Epidemiology and primary prevention of colorectal cancer].
AB  - The incidence of and mortality from colorectal cancer are increasing in Japan, as
      is its proportion among all malignant neoplasms. Thus, primary prevention of this
      cancer is crucial. Colorectal cancer is caused by interactions between host and
      environmental factors, with accumulation of gene alterations, such as activation
      of oncogenes and inactivation of suppressor genes, and generally involves an
      adenoma-carcinoma sequence. Carcinogenesis progresses with multi-factor, multi
      hit and multi-stage mechanisms. According to the report by WCRF/AICR, convincing
      preventive factors include eating vegetables (not fruit) and physical activity
      (colon only), while probable risk factors are red meat and alcohol. Possible
      preventive factors include dietary fiber, starch and carotenoids, whereas
      possible risk factors include high body mass, fat and heavily cooked meat. Such
      preventive and risk factors for colorectal cancer are discussed in this review.

PMID- 11242637
TI  - [Epidemiology of primary liver cancer in Japan].
AB  - In Japan, more than 90% of primary liver cancers consist of hepatocellular
      carcinoma (HCC), 80% of which is caused by chronic hepatitis C virus (HCV)
      infection, and the remaining 15% of which is caused by chronic hepatitis B virus
      (HBV) infection. The proportion of older patients among patients with HCC has
      been increasing in recent years because of the aging of the HCV-prevalent birth
      cohort born between 1925 and 1935. The cumulative risk of developing HCC among
      HCV carriers was estimated as 30% for males and 6% for females. Older age, being
      male, having a low platelet count, higher histological stage, genotype 1b, co
      infection with HBV, heavy drinking and smoking increase the risk of developing
      HCC among patients with chronic HCV infection. Recent reports on the efficacy of
      interferon therapy on the incidence of HCC in Japanese patients with chronic
      hepatitis C demonstrate the importance of providing a screening system for
      chronic HCV infection and establishing a medical referral system so that patients
      undergo the appropriate therapy for the Japanese HCV carriers.

PMID- 11242638
TI  - [Biliary tract cancer].
AB  - The proportion of mortalities from biliary tract cancer, which includes
      gallbladder and extrahepatic bile duct cancers, is only 5% of all deaths from
      malignant neoplasms in Japan. Epidemiologists, however, are concerned about the
      cancer due to its peculiar geographic distribution. In addition, they have also
      noted the recent decreasing trends in mortality rates, especially among females.
      The most probable explanation is either a change in the effects of risk factors
      or the development of abdominal ultrasound sonography and laparoscopic
      cholecystectomy, or both. Further research should be directed towards an analysis
      of the causes of this decreasing trend.

PMID- 11242639
TI  - [Pancreas cancer].
AB  - In Japan, the number of deaths due to pancreas cancer and its crude mortality in
      both males and females are increasing. Though the age-adjusted mortality of
      females seems to have reached a plateau, there might be an outbreak of this
      cancer in the future, since that young people nowadays like fast food, much of
      which contains considerable animal protein. There were significant correlations
      between the annual crude mortality of this cancer and the annual consumption of
      animal foods, animal protein and fat in Hokkaido from 1975 to 1997. Taking in
      less animal food and more plant food is important in the primary prevention of
      this cancer.

PMID- 11242640
TI  - [Lung cancer].
AB  - The number of lung cancer deaths in Japan has been continuously increasing for
      decades, mainly because of the growing size of the elderly population. In
      contrast, age-specific lung cancer death rates for those aged under 79 years
      plateaued recently, reflecting the decreasing smoking rates since 1966. However,
      the smoking rate for males (54% in 1999) is still extraordinarily high in Japan
      compared to other developed countries, so it is necessary to further promote anti
      smoking activities. It is reported that the relative risk for lung cancer due to
      cigarette smoking increases 4-5 fold (current smokers versus non-smokers) for
      males and 2-3 fold for females, and that the population attributable risk is 70%
      for males and 15-25% for females in Japan, which indicates that cigarette smoking
      is the most influential risk factor for lung cancer. However, the magnitude of
      the relative risk and population attributable risk is not as high as those
      observed in other developed countries. In order to clarify the reasons for this,
      it is necessary to further accumulate findings from actual epidemiological
      studies in Japan. In addition to cigarette smoking, occupational exposures,
      dietary habits (low intake of vegetables and fruits), atmospheric air pollution,
      environmental tobacco smoke, cooking and heating fuels, indoor radon and previous
      lung diseases are reported to increase the risk of lung cancer.

PMID- 11242641
TI  - [Epidemiology of breast cancer].
AB  - In Japan, the mortality rate from female breast cancer has increased in recent
      years. In 1998, the number of deaths from female breast cancer was 8,589,
      accounting for 7.7% of all female cancer deaths. The estimated number of new
      cases of female breast cancer in 1995 was 29,818, accounting for 15.3% of all
      sites, and its age-adjusted incidence rate was 39.8 per 100,000, ranking it top
      among the main sites of female cancer. As breast cancer is predicted to increase
      in the future, it is important for the primary prevention of breast cancer to
      avoid weight gain during adulthood, excess intake of fat, especially animal fat,
      and a high intake of alcohol. Physical activity and diets high in vegetables and
      fruits should be promoted.

PMID- 11242642
TI  - [Recent progress in epidemiologic research of uterine cancer].
AB  - Although the mortality and incidence of cervical cancer have been decreasing,
      those of uterine-body, or endometrial, cancer have been increasing. The
      proportion of endometrial cancer was reported to have become 33.6% of primary
      uterine cancers in 1995. Infection with certain types of human papilloma virus
      (HPV) is considered to be etiologically important for the occurrence of cervical
      cancer. Because HPV is sexually transmitted, some risk factors for cervical
      cancer are associated with certain kinds of sexual behavior such as a young age
      at first intercourse, multiple partners, and infrequent use of barrier-type
      contraceptives such as condoms. Frequent conceptions and deliveries and histories
      of sexually transmitted diseases like infection with herpes simplex virus type 2
      or chlamydia also have been suggested to be associated with the risk of cervical
      cancer. Smoking habits and infrequent intake of vegetables and fruits may be
      related to the increased risk of cervical cancer by supporting persistent
      infection of HPV through impaired immunological function. Although host factors
      such as a variant of a tumor suppressor gene like p53 have been assessed in terms
      of the risk of cervical cancer, these are not yet clearly elucidated. Estrogen
      stimulation of the endometrium unopposed by progesterone stimulation, namely,
      unopposed estrogen stimulation, is thought to be involved in the etiology of
      endometrial cancer. Frequent intake of animal fat, obesity or being overweight,
      infertility, and histories of diabetes mellitus, hypertension, and polycystic
      ovary syndrome have been reported to be risk factors for endometrial cancer, and
      they are thought to increase unopposed estrogen stimulation. Estrogen replacement
      therapy for postmenopausal symptoms, tamoxifen therapy for breast cancer, and
      taking sequential-type oral contraceptives have been shown to be exogenous risk
      factors for endometrial cancer in that they increase unopposed estrogen
      stimulation to endometrium.

PMID- 11242643
TI  - [Ovarian cancer].
AB  - Age-adjusted ovarian cancer deaths and mortality rates have increased annually in
      Japan from 1968 to 1995, with the absolute number of deaths increasing 4-fold
      during these years. Internationally, the mortality rates are high in North
      America or northern Europe, but their incidences have gradually decreased.
      However, the incidences of ovarian cancer have increased in France, Spain, and
      Japan. Risk factors for epithelial ovarian cancer include older age, being
      northern European or North American, family history of ovarian cancer,
      nulliparity, infertility, and obesity, and preventive factors include oral
      contraceptive use, gravidity, lactation, tubal ligation, and hysterectomy.

PMID- 11242644
TI  - [The epidemiology of prostate cancer--recent trends in prostate cancer incidence
      and mortality].
AB  - Prostate cancer is one of the major malignant diseases in Western countries. In
      Japan, the incidence and mortality of prostate cancer is not so high, but is
      continuously increasing. The recent drastic increase in incidence has been
      attributed to the growth of the elderly population, a westernized diet in daily
      life, widespread environmental contamination, and improved screening techniques
      such as the serum PSA test. The epidemiology of prostate cancer hints that its
      etiology is both environmental and genetic. Androgenic stimulation over time,
      perhaps due to a high fat diet, has been suggested as a cause of prostate cancer.
      Dietary factors such as phytoestrogens, vitamins and trace elements are suggested
      to have a protective effect against prostate cancer, and encourage us to search
      for means of prevention. Some have suggested that certain polymorphisms increase
      the risk of prostate cancer, whereas others are searching for genetic mutations
      that may also increase prostate cancer risk. The cause of prostate cancer is
      likely to be a combination of environmental and genetic factors.

PMID- 11242645
TI  - [Epidemiology of lymphoid and hematopoietic malignancies in Japan].
AB  - In general, the incidence and mortality rates for lymphoid and hematopoietic
      malignancies in Oriental countries, including Japan, are lower than in Western
      Europe and the U.S. However, those of lymphoid malignancies (ML) are clearly
      increasing in Japan, especially in the older generations. The main cause of the
      recent increment might be explained by compensation for risk reduction of
      infectious diseases in the old generations, so that their life span is extended
      rather than increment in exposure to specific risk factors. With regard to change
      in diagnostic criteria for ML, the geographical distribution of ML death rates by
      subtype shows variation over the last 20 years. In Japan, ML is more prevalent in
      southwestern districts, attributed to ATL caused by HTLV-I, and this high
      incidence of ATL should disappear with the HTLV-I eradication in the future. On
      the other hand, further diagnostic techniques might be developed and it is
      conceivable that a unique geographical distribution of new subtypes of lymphoid
      and hematopoietic malignancies may thereby be generated.

PMID- 11242646
TI  - [Study on the intensity of MMC and UFT in postoperative adjuvant chemotherapy for
      gastric cancer--study report of JFMTC Study No. 10].
AB  - The purpose of this study was to investigate the correlation between efficacy and
      dose intensity of postoperative adjuvant chemotherapy with MMC and UFT. A total
      of 1,410 patients from 180 institutions were allocated into a low-dose group and
      a high-dose group. The patients in the low-dose group received MMC at 8 mg/m2 on
      the day of surgery and 3 capsules of UFT (300 mg in tegafur) daily for 6 months.
      The patients in the high-dose group received MMC at 8 mg/m2 on the day of
      surgery, and in weeks 4, 10, 16, and 22 after surgery and 6 capsules of UFT (600
      mg in tegafur) daily for 6 months. The patients in the high-dose group tended to
      exhibit higher survival rates than those in the low-dose group, although the
      difference was not significant. For the n(+)ps(-) patients, however, the survival
      rates were significantly higher in the high-dose group (p = 0.043). The
      recurrence-free rates showed a similar tendency. The incidence rates of adverse
      events were significantly higher in the high-dose group than in the low-dose
      group. Compliance was poorer in the high-dose group. Although the number of
      adverse events increases, a better prognosis can be expected with a high dose.
      These results confirmed a dose-dependency in adjuvant chemotherapy with MMC and
      UFT.

PMID- 11242647
TI  - [Clinical evaluation of effects and improvement in quality of life from
      palliative therapy of combination chemotherapy with Furtulon and consecutive low
      dose cisplatin in cases of unresectable advanced gastrointestinal carcinoma].
AB  - Combination chemotherapy of Furtulon/low-dose cisplatin (CDDP) was administered
      to 13 patients with unresectable advanced gastrointestinal carcinoma (including 4
      cases of gastric cancer, 6 of colorectal cancer, 1 of pancreatic cancer, 1 of
      hepatic cancer, and 1 of esophageal cancer). All patients were unresectable due
      to poor performance status (PS > 3) or metastasis. They were treated with
      Furtulon 1,200 mg/day orally on days 1-10 followed by 4 drug-free days, every 2
      weeks, and CDDP 3.5 mg/m2/day, on days 1-5 by i.v. followed by 2 drug-free days
      every 4 weeks repeatedly. An average of 2-3 cycles were used. Six out of 13
      patients had a partial response, 5 had no change, and 2 had progressive disease.
      The response rate was 46% and median survival time was 320 days. After
      chemotherapy, there was an increase in appetite and body weight in 11 patients
      (85%), and the patients maintained a good performance status and quality of life.
      Moreover no renal dysfunction occurred after treatment with CDDP. There was no
      high-grade toxicity over grade 2, only slight nausea, vomiting and diarrhea. From
      the present study, combination chemotherapy of Furtulon/low-dose CDDP seems to be
      effective for patients with advanced gastrointestinal cancer, and to have
      improved their quality of life (QOL).

PMID- 11242648
TI  - [Antitumor effect of the plant alkaloid preparation, cepharanthin].
AB  - The antitumor effect of cepharanthin (CR), a biscoclaurine alkaloid, was examined
      as to its direct action on tumor cells and inhibitory action on angiogenesis in
      tumors. The effect of CR on in vitro invasion by murine RL-[symbol: see text] 1
      leukemia cells and Colon 26 tumor cells was studied using a biocoat matrigel
      invasion chamber. One hundred micrograms/ml of CR inhibited tumor cell invasion.
      Early induction of apoptosis was assayed by the binding of annexin V and
      phosphatidylserine (PS) in the cellular membrane CR (10 and 100 micrograms/ml)
      induced apoptosis in human Daudi and Raji B lymphoblastoid cells. Treatment with
      CR (1 and 10 micrograms/ml) also inhibited the in vitro growth of Daudi and Raji
      cells. Ten micrograms/ml of CR also inhibited the growth of human umbilical vein
      endothelial cells (HUVEC) and human dermal microvascular endothelial cells
      (HMVEC). These results indicate that CR has diversified antitumor functions,
      i.e., an enhancement of a sequential immune mechanism, a direct cytotoxic effect
      and inhibitory action of angiogenesis in tumors.

PMID- 11242650
TI  - [A case of lung and pleural metastases from breast cancer responding to
      toremifene].
AB  - A patient with lung and pleural metastases from breast cancer treated effectively
      with toremifene is reported. A 62-year-old woman underwent mastectomy for breast
      cancer, and had high levels of estrogen and progesterone receptor. After 2-years
      of adjuvant UFT therapy, lung and pleural metastases were seen on a chest x-ray.
      The patient received a high-dose of toremifene (120 mg/day). After five months
      with toremifene, a chest x-ray and CT scan showed the disappearance of lung and
      pleural metastases. No recurrence or metastases have been detected for twenty
      months to date. No serious side effects were noticed. High-dose toremifene might
      be an effective therapy for cases of postmenopausal metastatic breast cancer,
      with high levels of estrogen and progesterone receptor.

PMID- 11242649
TI  - [Advanced breast cancer with multiple bone metastases successfully treated with
      combined chemoendocrine-therapy of CEF (cyclophosphamide, epirubicin, 5
      fluorouracil) and 5'-DFUR (5'-deoxy-5-fluorouridine) + MPA (medroxyprogesterone
      acetate)--a case report].
AB  - We report the case of a 51-year-old female with stage IV advanced breast cancer
      accompanied by multiple bone metastases. A hard mass of about 3.0 cm in diameter
      was palpated just below the nipple. An excisional biopsy was performed and
      histological examination revealed infiltrated solid tubular adenocarcinoma. There
      were no estrogen or progesterone receptors in the tumor. Modified radical
      mastectomy was performed in October, 1998. Postoperative adjuvant therapy with 10
      cycles of CEF therapy was undertaken for one year. Combined chemoendocrine
      therapy with 5'-DFUR and MPA was also conducted for 11 months. Bone scintigraphy
      showed that all bone metastatic lesions disappeared completely one year after the
      operation. Mild bone marrow suppression, alopecia and body weight gain were
      observed as side effects. It is suggested that this combination therapy may be
      useful for advanced breast cancer patients with multiple bone metastases.

PMID- 11242651
TI  - [A breast cancer patient with recurrence in the thoracic wall in whom a high-dose
      of toremifene was effective].
AB  - The patient was a 53-year-old female who presented with a primary complaint of
      reddening of the left precordial skin. She had undergone mastectomy for cancer of
      the left breast 12 years and 4 months earlier and had received endocrine
      chemotherapy including TAM as a postoperative adjuvant therapy. A diagnosis of
      thoracic wall recurrence was made by chest CT and pathological examination of
      skin biopsy specimens. Toremifene (TOR) was administrated at 120 mg/day, and PR
      was maintained for 8 months. Even after the condition became PD, the patient has
      retained adequate QOL with combination therapies including radiotherapy, and is
      still treated on an outpatient basis 3 years after the beginning of the
      treatment.

PMID- 11242652
TI  - [Two cases of advanced and metastatic breast cancers treated by docetaxel in
      combination with intra-arterial infusion of adriamycin].
AB  - Two cases of advanced and metastatic breast cancers were treated by docetaxel
      (TXT) in combination with intra-arterial infusion of adriamycin (ADM). Patients
      received 60 mg/body TXT i.v. and 30 mg/body ADM ia (AT therapy) bi-weekly.
      Clinical responses were observed in these two patients and the durations of
      responses were over 20 weeks. Critical toxicities of grade 2 leukopenia and
      alopecia were observed but grade 4 severe toxicities were not. Thus AT therapy
      can be easily and safely performed with outpatients. This therapy can improve the
      response rate and time to progression; therefore phase I or phase I/II clinical
      trials of AT therapy in Japan are recommended.

PMID- 11242653
TI  - [Induction chemotherapy (cisplatin + vinorelbine) is found to be markedly
      effective for squamous cell lung carcinoma with sarcoidosis--a case report].
AB  - A sixty-one-year-old man was admitted to our hospital because of a right lung
      tumor shadow. He had been diagnosed as having sarcoidosis at the age of fifty
      seven. He was newly diagnosed as having squamous cell carcinoma by trans
      bronchial biopsy. He was treated with an induction chemotherapy (cisplatin 80
      mg/m2 + vinorelbine 20 mg/m2) followed by right middle and lower lobectomy with a
      mediastinal nodal dissection, because the stage of his carcinoma was cT2N2M0.
      Resected lung tissue showed the disappearance of cancer cells. Dissected
      mediastinal and hilar lymph nodes showed many sarcoid granulomas. Cisplatin
      combined with vinorelbine might be an effective chemotherapy for non-small cell
      lung carcinoma.

PMID- 11242654
TI  - [A trial with single-agent vinorelbine in taxane-resistant non-small cell lung
      cancer].
AB  - It is reported that the single-agent administration of vinorelbine (VNR) is
      improper in salvage therapy for non-small cell lung cancer. However, there are
      few reports on its use as second line in taxane-containing chemotherapy. We used
      single-agent VNR administration for nine cases of taxane-resistant non-small cell
      lung cancer, and an antitumor effect was seen in four cases. We present three of
      these cases. A factor for the high response rate is considered to be that vinca
      alkaloid is not used as a pre-treatment. Moreover, VNR may be effective even if
      there is a gene mutation for beta tubulin, which causes taxane resistance.

PMID- 11242655
TI  - [A case of gastric cancer with liver metastases successfully treated with
      combination therapy of systemic and hepatic arterial infusion chemotherapy].
AB  - A 67-year-old man was admitted to our hospital because of advanced gastric cancer
      associated with metastases to the liver, the lymph nodes along the lesser
      curvature and the infradiaphragmatic lymph nodes. As we considered the primary
      lesion and the liver metastases to be unresectable, we treated him with
      combination therapy of systemic and hepatic arterial infusion chemotherapy. The
      regimen of systemic chemotherapy consisted of cisplatin (CDDP) and UFT. Hepatic
      arterial infusion chemotherapy included 5-fluorouracil (5-FU), doxorubicin (DXR)
      and mitomycin C (MMC). We repeated this therapy six times. The size of the
      primary lesion and the lymph node metastases decreased significantly after the
      chemotherapy. The size of the liver metastases did not change, but they appeared
      to necrotize. The patient maintained a good quality of life during the therapy.
      He finally died of peritonitis carcinomatosa 18 months after the diagnosis. This
      case indicated that combination therapy of systemic and hepatic arterial infusion
      chemotherapy was effective in cases of unresectable gastric cancer associated
      with liver metastases.

PMID- 11242656
TI  - [Complete response of a massive hepatocellular carcinoma with lung metastasis to
      UFT (DPD inhibitory fluoroprymidines: DIF)].
AB  - A 77-year-old man was referred to our hospital because a periodic examination for
      hepatitis C cirrhosis and diabetes mellitus at a nearby clinic had revealed an
      elevated AFP level. Abdominal ultrasound and CT scan revealed a giant tumor in
      the right hepatic lobe, and a diagnosis of hepatocellular carcinoma was made with
      a biopsy. A pulmonary CT scan also revealed a diffuse granular shadow in the
      right lung field, leading to a diagnosis of multiple pulmonary metastases from
      the hepatocellular carcinoma. Arterial infusion chemotherapy was performed, but
      was ineffective. Thus, the administration of 600 mg/day of UFT was initiated.
      Both the AFP and PIVKA-2 levels, which had been increasing, returned to normal 3
      months later. Ultrasound and CT scan showed that the hepatocellular carcinoma and
      lung metastatic foci had disappeared completely. The administration of UFT
      therefore appears promising for the treatment of hepatocelluar carcinoma and can
      be used safely, even with patients in poor general condition.

PMID- 11242657
TI  - [A case of advanced hepatocellular carcinoma with portal invasion resected after
      treatment by continuous intra-arterial chemotherapy with cisplatin and 5
      fluorouracil].
AB  - A 67-year-old male diagnosed as having inoperable advanced hepatocellular
      carcinoma with portal invasion was able to undergo resection after continuous
      intra-arterial chemotherapy with 5-fluorouracil (5-FU) and cisplatin (CDDP).
      These were continuously administered for 24 hours at doses of 5-FU of 250 mg and
      CDDP of 5 mg/day, from day 1 to day 5 in a week, repeated 6 times. In additions
      to the reductions of the levels of AFP and PIVKA-II from 212.6 ng/ml and 16,100
      mAU/ml to 11.8 ng/ml and 12 mAU/ml, respectively, the volume of the tumor and the
      portal invasion were diminished remarkably. As a result, a left extended
      hepatectomy could be performed. No sign of recurrence was seen during 16 months
      of follow-up after the operation. Given the above results, continuous intra
      arterial chemotherapy with 5-FU and CDDP therapy may be effective for patients
      with hepatocellular carcinoma.

PMID- 11242658
TI  - [A case report of radiation-induced cancer of the buccal mucosa, effectively
      treated with CF therapy].
AB  - We report favorable effect of combination chemotherapy with CDDP and 5-FU for a
      case of radiation-induced cancer of the left buccal mucosal membrane. A 71-year
      old man underwent external-beam radiotherapy for a squamous cell carcinoma of the
      tongue. He developed left buccal mucosal cancer 13 years after the start of this
      radiotherapy. One course of the therapeutic regimen consisted of CDDP 70
      mg/m2/day drip infusion for 2 hours (day 1) and 5-FU 700 mg/m2/day drip infusion
      for 120 hours (days 1-5). The patient underwent 4 courses. A partial response was
      achieved after 1 course, after which additional treatment with the same regimen
      was made with favorable effect. Four years after the treatment, 2 courses of the
      same chemotherapy were performed because of a recurrence of radiation-induced
      cancer, with a complete response. No serious side effects appeared. A
      histopathological examination of the lesion showed no cancer tissue. The patient
      was alive and cancer free 4 years after the treatment, and has been followed.

PMID- 11242659
TI  - [Guideline for phase I study on new anticancer agents].
AB  - Since more than 50% of patients with cancer could no be cured by present standard
      therapy, new effective anticancer agents are needed in clinical level. In the
      evaluation of new anti-cancer agents by phase I study, there are several
      important and specific issues from scientific, medical, statistical, and ethical
      view points. Clinical safety data management is critically important in phase I
      study. This paper shows major parts of a report entitled "Guideline for phase I
      study on new anticancer agents", already published in JPs Pharmacol Ther 26: 441
      454, 1998, with minor modification in order to answer these issues.

PMID- 11242660
TI  - [What is the direction of pediatrics today?].

PMID- 11242661
TI  - [Serious life events and congenital malformations. A national study with a
      complete follow-up].
AB  - INTRODUCTION: Emotional stress during organogenesis could, in theory, cause
      congenital malformations by increasing the level of cortisone, but documentation
      is lacking. We undertook a follow-up study to test the hypothesis that
      psychosocial stress increases the prevalence of malformations, in particular
      malformations of the cranial neural crest. MATERIAL AND METHODS: We defined
      serious life events as the death or first hospital admission for cancer or acute
      myocardial infarction of partners or children. All women exposed to severe life
      events during and up to 16 months before pregnancy in the period 1980 to 1992
      were identified by means of five national registers. We studied 3560 exposed
      pregnancies and randomly selected 20,299 "not-exposed" pregnancies as the control
      cohort. RESULTS: Women exposed to severe life events gave birth to offspring with
      an increased prevalence of cranial neural crest malformations, at an adjusted
      odds ratio of 1.54; 95% CI (1.05-2.27). For other malformations the adjusted odds
      ratio was 1.14-95% CI (0.94-1.42). Women exposed in two consecutive pregnancies
      had a higher odds ratio for cranial neural crest malformations, with an adjusted
      odds ratio of 2.99; 95% CI (1.06-8.43). Death of an older child during the first
      trimester was associated with an adjusted odds ratio of cranial neural crest
      malformations in the offspring of 4.75; 95% CI (1.63-13.78). Unexpected death of
      a child during the first trimester was associated with an adjusted odds ratio of
      8.36 in the offspring, 95% CI (2.41-28.99) for cranial neural crest malformations
      and 3.64, 95% CI (1.29-10.32) for other kinds of malformations. DISCUSSION AND
      CONCLUSION: These findings support the hypothesis that severe emotional stress
      during pregnancy, especially stress related to the death of a child, may cause
      congenital malformations, particularly those of the cranial neural crest.

PMID- 11242662
TI  - [Neonatal mortality and morbidity in gestational age shorter than 30 weeks for
      babies treated primarily in a central hospital. Follow-up studies of an
      unselected, consecutive patient group].
AB  - AIM: The aim of the study was to investigate the mortality and morbidity of very
      premature babies treated at a Danish county hospital in the mid-1990s. MATERIALS
      AND METHOD: The 62 survivors of 70 consecutive babies born in 1993-1997 were
      given a neuropaediatric follow-up examination at a corrected mean age of 49 (22
      69) months. The mean gestational age was 27 (24-29) weeks and the mean birth
      weight was 1012 (550-1374) g. RESULTS: Eight babies (11%) died within 28 days of
      birth. Four (6%) had an intracerebral haemorrhage, grade 3-4; four (6%) had
      retinopathy of prematurity; and three (4%) had bronchopulmonary dysplasia at 36
      weeks of gestation. Four of the survivors developed cerebral palsy. Two of these
      babies and a neurologically normal baby had visual impairments. None developed
      epilepsy. DISCUSSION: Thus, our babies had a low mortality and only a few
      complications at long-term follow-up. Early nasal continuous positive airway
      pressure and early supplementation with a surfactant seem to be essential for
      these positive results in our most premature babies.

PMID- 11242663
TI  - [Individualized cancer treatment. Illustrated by acute lymphoblastic leukemia in
      children].
AB  - The intensity of treatment in children with acute lymphoblastic leukaemia has
      conventionally been based on risk group stratification, which reflected the
      patient's age and white cell count at diagnosis, as well as the immunophenotype
      and presence of certain high risk chromosomal aberrations. Identification of the
      latter has often failed, owing to the very selective demands for lymphoblast
      culture. Nevertheless, the risk-adapted and very intensive antileukaemic therapy
      has been a success, with cure rates as high as 75-80 per cent. However, a large
      fraction of these patients are overtreated. A more individualiZed tailoring of
      the therapy is expected to be available through: 1) A series of new and more
      direct techniques to reveal chromosomal aberrations; 2) exploration of the in
      vitro drug sensitivity of the malignant clone; 3) detailed monitoring of the
      minimal residual disease down to the level of one leukaemic cell in 10,000
      100,000 normal bone marrow cells; 4) therapeutic drug monitoring and individual
      dose adjustments; and 5) mapping of the individual patient's risk of serious or
      even life-threatening side effects. It is likely that these approaches would
      allow a reduction in the treatment intensity for most patients, thereby reducing
      the risk of serious toxicity, and concomitantly improve identification of those
      patients for whom standard therapy is likely to fail and who are thus candidates
      for stem cell transplantion or experimental therapy in first remission.

PMID- 11242664
TI  - [Intersex: which gender should be chosen?].
AB  - A newborn infant with ambiguous genitalia is a medical emergency, and the choice
      of gender must take into account both the chromosomal and the gonadal sex, the
      hormonal milieu during fetal life, surgical aspects, the anatomy of the internal
      genitalia, as well as the prospects for future fertility, normal psychosexual
      development, and sexual function as an adult. Counselling requires paediatric
      endocrine, surgical, and psychological expertise, but the lack of knowledge of
      the long-term consequences of an intersex condition hampers rational treatment.
      It has long been customary to assign the child a female gender, whereas recent
      research points to a choice of a gender compatible with the chromosomal sex, if
      at all possible. This article reviews our knowledge in this field.

PMID- 11242665
TI  - [Diagnostic benefit of gastrointestinal endoscopy in infants under one year of
      age--a two-year survey].
AB  - INTRODUCTION: Gastrointestinal endoscopy in children is a well-established
      procedure. We reviewed our experience of endoscopy in infants below one year of
      age to evaluate indications, endoscopic findings, histology, and complications.
      MATERIAL AND METHODS: Twenty-eight infants were studied over a two-year period.
      Of these, 18 underwent upper endoscopy, six recto/sigmoidoscopy or colonoscopy,
      and four both procedures. RESULTS: The most common indication (10/22) for upper
      endoscopy was vomiting and suspicion of gastrooesophageal reflux disease. In
      these infants, 24-hour continuous monitoring of the oesophageal pH followed the
      procedure. Indications for lower endoscopy were rectal bleeding (n = 6) and
      intractable diarrhoea (n = 4). There were no complications to anaesthesia,
      endoscopy, or biopsy. Overall, there were endoscopic abnormalities in 82% and
      histological abnormalities in 75% of the infants. The diagnostic findings
      included rare disorders, such as eosinophilic gastroenteritis, microvillous
      inclusion disease, and chylomicron retention disease. Diagnosis of these diseases
      requires gastrointestinal biopsy. DISCUSSION: Gastrointestinal endoscopy is a
      safe procedure, which is a valuable part of the diagnostic work-up in a selected
      group of infants with long-lasting or severe gastrointestinal symptoms.

PMID- 11242666
TI  - [Accidents in day care institutions in Denmark during the 1990's].
AB  - INTRODUCTION: This paper analyses the development in the incidence of injuries in
      day care institutions for children below school age in Denmark 1989-1997.
      MATERIAL: Data on injuries were collected from the injury register, which covers
      around 15 per cent of the Danish population. The population data derive from
      Statistics Denmark. METHOD: Incidence patterns were analysed by means of linear
      regressions and comparisons of means. RESULTS: Injuries in day care institutions
      for children below school age have increased sharply during the 1990s. In
      children aged 1-6, the 3-6-year-olds had a higher incidence and the boys a
      significantly higher incidence of injury than the girls. DISCUSSION: The increase
      in injuries is to some extent explained by a higher attendance at day care
      institutions. The hypothesis that the rising incidence is partly due to an
      increase in the tendency to seek emergency department treatment in the event of
      minor injuries cannot be ruled out, as minor injuries almost solely account for
      the rise.

PMID- 11242667
TI  - [Teaching and counseling families with small children in an urban area about
      minor illnesses of childhood].
AB  - INTRODUCTION: Parents' knowledge of and experience with illness in their children
      are often limited. They find it difficult to take the responsibility when their
      children are ill. They seek help immediately from the health care system,
      although the symptoms are mild. We wanted to discover whether teaching parents
      about minor illness in children and counselling over the telephone during acute
      illness would mean that parents sought help less often from the health care
      system, when their children became ill. This article deals with the teaching of
      the parents. MATERIAL AND METHODS: The project had an intervention group of 91
      children aged 12-35 months and a control group of 400 children aged 9-33 months.
      The intervention group was instructed for two hours twice in the local day
      nursery and telephone counselling from a nurse trained in children's acute
      illnesses was made available from 4 pm to 11 pm on weekdays and from 10 am to 11
      pm at weekends during the period 20th October 1998 to 1st May 1999. RESULTS: No
      visible change was seen in the use of the health care system in either group, but
      there was a small change in favour of the intervention group in the use of a
      general practitioner instead of calling the emergency medical service. Eighty per
      cent of the counselling dealt with common acute illnesses; 75% ended without
      referral. DISCUSSION: There was no visible difference in the use of the health
      care system in either group. Parents were happy with the offer of teaching and
      telephone counselling, but it should have been given when the infants started at
      the nursery. They felt their children were too old at the time the project
      started. We suggest a continuation of antenatal classes in the form of "parent
      preparation classes", where one subject could be minor acute illnesses in
      children.

PMID- 11242668
TI  - [Why do parents of small children visit casualty ward when their children suffer
      of acute illness?].
AB  - INTRODUCTION: People in big cities tend to use the casualty ward instead of their
      own doctor or the emergency service. This is both more expensive and an
      inappropriate use of the health care system in Denmark. We wanted to find out why
      parents used the casualty ward and to look for an alternative way of helping
      parents during minor acute illnesses in their children. MATERIAL AND METHOD: One
      hundred questionnaires were distributed in the paediatric ward of Rigshospitalet,
      Copenhagen, from 28.1.1999 to 9.4.1999 to parents who came to the casualty ward
      without a referral from a doctor. Only people who could speak Danish
      participated. RESULTS: Seventy-five percent had no referral from a doctor, the
      rest were verbally referred by a doctor. Twenty-five percent came to the casualty
      ward while their own doctor was on duty. Thirty-nine percent chose the casualty
      ward, because the staff had a special knowledge of children. Most parents wanted
      to have their children examined by a paediatrician. DISCUSSION: Parents need to
      be educated in the proper use of the health care system when their children are
      ill. Many use the casualty ward for convenience and to get expert knowledge about
      their children's illness, even when it is not necessary. We suggest that an
      experienced children's nurse should work with the emergency service, so as to
      keep children with minor, acute illness out of the casualty ward.

PMID- 11242669
TI  - [Emergency transport of newborn infants--fetch or bring?].
AB  - INTRODUCTION: Neonatal transport is difficult and often associated with problems.
      In 1998, the Neonatal Intensive Care Unit, University Hospital of Copenhagen, H:S
      Rigshospitalet, set up a neonatal transport team. The aim of this study was to
      assess whether a better quality of high risk transport could justify the
      increased consumption of time. METHOD: The schedules for observation and
      assessment filled in by the transport team were collected and compared with
      records of the transport of high-risk neonates by local transport. The comparison
      consisted in the number of infants, severity of the problems, interventions
      carried out either locally or after arrival at the Neonatal Intensive Care Unit,
      and the condition of the infants judged on the pH, blood sugar level, blood
      pressure, and body temperature. RESULTS: The neonatal transport team fetched 68
      high-risk infants, whereas 140 high-risk infants were brought by local transport.
      Infants fetched by the transport team were more sick, both before and during
      transport, than those brought to us. On arrival at the Neonatal Intensive Care
      Unit, more infants brought by local transport had problems (31% vs 16%): 12 (9%)
      transports had more than one critical problem, in contrast to none of the infants
      fetched by the transport team. The transport team carried out 71 interventions on
      44 of the 68 infants (65%). These interventions explain the better condition of
      the infants on arrival. Acute interventions soon after arrival at the Neonatal
      Intensive Care Unit were carried out on 91 of the 140 infants brought by local
      transport (65%). DISCUSSION: Neonatal transport of extremely ill infants is
      difficult. A specialised (transport) team with local stabilisation and transport
      reduces the frequency of complications. The number of high-risk neonates
      transported is so small that it is improbable that adequate expertise can be
      built up and maintained locally.

PMID- 11242671
TI  - [Parents of children with febrile convulsions. Multidisciplinary quality
      development of information and documentation].

PMID- 11242670
TI  - [Febrile convulsions, Treatment and prognosis].
AB  - Epidemiological data indicate that the long-term prognosis in the vast majority
      of children with febrile seizures is good. Three main problems are important for
      the treatment: febrile seizures are extremely upsetting for the parents, the
      recurrence rate is 30-40% and the febrile status occurs unpredictably and is
      potentially damaging to the CNS. There is universal agreement that daily
      prophylaxis with valproate, primidone, or phenobarbital should only be used in
      highly selected cases, if at all. The effectiveness of phenytoin and
      carbamazepine has not been documented. Antipyretic treatment does not reduce the
      recurrence rate. Intermittent diazepam prophylaxis at times of fever may or may
      not reduce the recurrence rate significantly, but there is no data to suggest
      that it improves the long-term outcome, as compared with short-term seizure
      control, in terms of IQ, cognition, academic progress, motor control, and
      subsequent epilepsy. Acute anticonvulsive treatment with rectal diazepam in
      solution or other benzodiazepines is effective in aborting recurrent seizures
      with almost the effectiveness of i.v. treatment and is safe, simple, and easy to
      use for the parents. The long-term prognosis is probably uninfluenced by the type
      of treatment given in early childhood. It has not been established that acute
      anticonvulsive treatment with benzodiazepine is better than placebo.

PMID- 11242672
TI  - [Infant psychiatry].
AB  - Infant psychiatry is a discipline concerned with diagnostic assessment,
      treatment, and prevention of mental health problems in infancy and early
      childhood. A new diagnostic framework: Zero to three (DC 0-3) has been designed
      to complement the ICD 10/DSM IV, including new diagnostic categories, and a
      multiaxial construct addressing developmental and relational aspects. Prevalence
      and outcome for mental retardation and pervasive developmental disorders are well
      known. Our knowledge of variations in attachment patterns, disorders of
      neurophysiological regulation, eating disorders, failure to thrive, emotional,
      affective, and behavioural problems, disorders of relating and communication, and
      eventually parent-child relationship disorders is still incomplete. It is
      recommended to use video and combine clinical evaluation with structured tests in
      assessment. Intervention may include guidance, psychoeducation, psychotherapy, as
      well as social and educational support. Parent-child relationship treatment seems
      effective. Evaluating intervention and treatment raises immense methodological
      problems. Future research should address how risk and resilience interacts in the
      psychopathological process and enhance our knowledge of effective intervention
      strategies.

PMID- 11242674
TI  - [Evidence-based treatment of ADHD/DAMP in children and adolescents with central
      stimulants].
AB  - The use of stimulants in the treatment of children and adolescents with Attention
      Deficit Hyperactivity Disorder, ADHD, and Deficit in Attention, Motor Control and
      Perception, DAMP, is often considered somewhat controversial. It was first used
      in 1937, and since the 1960s, 3000 published studies and 250 reviews have
      demonstrated the positive, short-term effect of stimulants on children and
      adolescents with ADHD/DAMP. More than 160 randomised, controlled trials (RCT)
      have studied the effect of attention, hyperactivity, and impulsivity.
      Furthermore, stimulants have proved effective on the social relation of such
      children, both in their families and in with their peers. Side effects are often
      mild, transient and dose-related. The short-term effectiveness of stimulants is
      thus well-documented and their prescription evidence-based, whereas further
      studies on the long-term effect are needed.

PMID- 11242673
TI  - [Infant and child psychiatry in Denmark].
AB  - INTRODUCTION: A descriptive epidemiological study of children aged 0-36 months.
      METHODS: Diagnoses reported from the child psychiatric departments to The
      National Psychiatric Register were collected from a three-year period 1996, 1997,
      and 1998. The child psychiatric departments in Denmark filled in a questionnaire
      concerning referral, assessment, treatment, and consultant/liason functions. All
      the child psychiatric departments took part in the study. RESULTS: 529 children
      aged 0-3 years were reported to the National Psychiatric Register. In the period
      studied, there was a 30% increase in the number of children reported. Adjustment
      reactions were the commonest diagnosis in the youngest children, aged 0-12
      months. Pervasive developmental disorders, particularly infantile autism, were
      commonest used in the age group 2-3 years. Twenty-four per cent of the children
      reported, especially the youngest children, had no specific psychiatric
      diagnosis. The increase in the number of children aged 0-1 year with adjustment
      reactions and non-specific diagnoses is discussed. Children aged 0-3 years are
      mainly treated as outpatients or by a consultant/liason child psychiatric
      service. The children referred to the child psychiatric departments in 1997
      varied from fewer than 10 to about 100 children. Infant psychiatric units were
      established in two places in Denmark, in 1992 and 1997. DISCUSSION: The
      increasing number of children aged 0-3 years reported to the National Psychiatric
      Register in the period 1996-1998 reflects an increase in the children aged 2-3
      years diagnosed with pervasive developmental disorders, and in the case of the
      youngest children, aged 0-1 year, a more extensive child psychiatric intervention
      in relation to populations at risk, such as infants with mentally ill mothers.

PMID- 11242675
TI  - [Children and stress].

PMID- 11242676
TI  - [Picture of the month: zinc deficiency].

PMID- 11242677
TI  - [Birth weight and blood pressure].

PMID- 11242678
TI  - [Can PET be a cost-effective diagnostic method?].

PMID- 11242679
TI  - [Guidelines for antibiotic use in the Laegeforeningens Medicinfortegnelse 2000].

PMID- 11242680
TI  - [Support to Danish antibiotic policy].

PMID- 11242681
TI  - [Sclerosis can be stopped].

PMID- 11242682
TI  - [Advertising over the boundaries].

PMID- 11242683
TI  - [NutraSweet--aspartame].

PMID- 11242684
TI  - Influenza in the world. 1 October 1999-30 September 2000.

PMID- 11242686
TI  - Dead right or dead wrong?

PMID- 11242685
TI  - Health conditions for travellers to Saudi Arabia.

PMID- 11242687
TI  - Influenza vaccine distribution.

PMID- 11242688
TI  - One physician's view of voting rights, responsibilities and election reform.

PMID- 11242689
TI  - Asthma in Missouri: recent trends and sociodemographic risk factors.
AB  - This study describes recent trends in asthma morbidity and mortality rates across
      Missouri, and identifies several population-based risk factors that account for
      the geographic variation in asthma hospitalizations and emergency room visits
      among counties. The percentage of African-American residents was the best
      predictor of high asthma treatment rates, explaining 77% of the variation in
      hospitalizations and 57% of the variation in ER visits. All other
      sociodemographic predictors combined explained less than 10% of the statewide
      variation in rates.

PMID- 11242690
TI  - Screening for cervical cancer in India.

PMID- 11242691
TI  - Delay in presentation of oral cancer: a multifactor analytical study.
AB  - BACKGROUND: Patients with oral cancer often present late to the doctor making
      treatment difficult, expensive and sometimes unsuccessful. Delay in presentation
      may be considered to be a health risk-taking behaviour. The present study
      analyses the psychosocial factors related to delay in presentation of oral cancer
      patients through the Triandis' model of health-seeking behaviour and also
      examines the relationship between delay and the stage of cancer. METHODS: Seventy
      nine oral cancer patients were interviewed after evolving a valid and reliable
      questionnaire, and determining the sample size. Univariate and multivariate
      logistic regression analysis was applied between demographic variables,
      psychosocial factors, primary delay (defined as delay between the first symptom
      and the seeking of medical advice), secondary delay (interval between the first
      consultation and presentation at the medical college), tertiary delay (delay in
      definitive treatment even after being seen at a tertiary care centre) and stage
      of the disease. Multiple logistic regression was also carried out. RESULTS:
      Primary delay ranged from less than a week in 5 (6.3%) patients to more than 1
      year in 8 (10%) patients. A linear relationship was found between primary and
      secondary delay (F-statistic p < 0.0152). A majority of patients (70.9%) had
      advanced oral cancer. The stage of cancer at presentation to the hospital was
      significantly related to primary (G-test 6.3; p < 0.0121) but not to secondary
      delay. Multivariate analysis revealed that five variables, 'ill fated to have
      cancer', 'cancer a curse', 'non-availability of transport', 'trivial ulcers in
      mouth are self-limiting' and 'prolonged treatment renders family stressful' were
      significant independent predictors of primary delay. CONCLUSION: The identified
      independent predictors of primary delay should be used to develop the main theme
      of an educational intervention programme for patients with oral cancer.

PMID- 11242692
TI  - Pre-transplant risk factors for renal allograft dysfunction at one year in Indian
      patients.
AB  - BACKGROUND: Only a few patients with end-stage renal disease in the Indian
      subcontinent receive optimal treatment. Of these only a minority can afford a
      second renal transplant. Awareness of modifiable pre-transplant risk factors that
      influence allograft function is crucial before embarking on the first transplant.
      There are no reports from the Asian subcontinent describing the pre-transplant
      risk factors. METHODS: We studied the effect of donor age, gender, and relation
      with the recipient, patient age, gender, HLA matching, native kidney disease and
      immunosuppression on one-year allograft function using data from 1177 consecutive
      primary living related donor renal transplants at the Christian Medical College
      Hospital, Vellore. We performed a univariate followed by a multivariate analysis
      using a logistic regression model to calculate the odds ratio for the effect of
      the above factors on two levels of graft function (serum creatinine > 1.4 mg/dl
      and > 2 mg/dl) at one year. RESULTS: On univariate analysis, older donors, women
      donors, mother being the donor, men recipients, < 1 HLA antigen match,
      cyclosporine-based immunosuppression and patient age between 16 and 40 years were
      associated with serum creatinine levels > 1.4 mg/dl at one year. Multivariate
      analysis showed that donor-related factors, namely mother as donor, older donors,
      and a < or = 1 HLA antigen match, were risk factors for graft dysfunction (serum
      creatinine level > 1.4 mg/dl) at one year. Recipient-related risk factors were
      male patients and those between the age of 16 and 40 years. CONCLUSION: In
      patients undergoing living related donor renal transplants from large extended
      families, a younger haplomatched donor, for instance, a brother, is a better
      choice than an older haplomatched donor, for instance, the mother, particularly
      in young male recipients at a higher risk of renal dysfunction.

PMID- 11242693
TI  - Antibody response to a single tetanus toxoid booster in young women in rural
      south India.
AB  - BACKGROUND: Tetanus toxoid immunization is an integral part of the maternal and
      child health programme in developing countries. It is likely that many women may
      have had childhood immunization and so already have antitetanus antibodies at the
      time of their first antenatal visit. A single dose of tetanus toxoid injection
      can boost the levels of antitetanus antibodies in these women. This study was
      undertaken to assess the previous immunization status by verbal history and
      assess the effect of a single tetanus toxoid injection in young women. METHODS:
      Ninety-nine unmarried women between 18 and 22 years of age were enrolled for the
      study. The history of childhood immunization was obtained from their mothers.
      Blood samples were collected to measure IgG antibody levels to tetanus using
      ELISA. Antibody levels were also measured on day 14 after a dose of tetanus
      toxoid injection. RESULTS: Of the 99 women studied, 81 had a history of childhood
      immunization while 18 did not. Overall, 92% of the women had protective levels of
      antibodies at the time of first testing and 99% of the women were protected with
      a single dose of tetanus toxoid. CONCLUSION: In areas with good maternal and
      child health services, a single booster dose of tetanus toxoid can be considered
      adequate for primigravidae with a history of childhood immunization.

PMID- 11242694
TI  - Clinical profile and prognosis of Addison's disease in India.
AB  - BACKGROUND: The clinical presentation of primary adrenocortical insufficiency
      (Addison's disease) in India may differ from that in developed countries. We
      therefore studied the clinical profile and prognosis of Addison's disease, with
      special reference to patients with tuberculous infection. We also evaluated the
      utility of various clinical parameters in differentiating tuberculous from
      idiopathic Addison's disease. METHODS: In a retrospective and prospective study,
      45 consecutive patients of Addison's disease (20 patients with tuberculous
      aetiology) were studied for their clinical features, autoantibody profile
      (adrenal cytoplasmic, thyroid microsomal and gastric parietal cell antibodies)
      and prognosis. RESULTS: A tuberculous aetiology was present in 47% of the
      patients and of these, 85% had enlargement of one or both adrenal glands. While
      patients with tuberculous Addison's disease had a higher prevalence of extra
      adrenal tuberculosis (55% v. 9%, p = 0.001), a lower frequency of adrenal
      cytoplasmic antibodies (17% v. 50%, p = 0.03) and parietal cell or thyroid
      microsomal antibodies (11% v. 55%, p = 0.004), a considerable overlap was
      observed. Despite adverse circumstances, during a mean follow up of 3.3 years,
      only 2 (5%) patients died, neither of whom had tuberculous involvement. Five
      (13%) patients suffered from one or more episodes of Addisonian crises, though
      none of these resulted in mortality. CONCLUSION: Tuberculosis remains an
      important cause of Addison's disease in India. The presence of extra-adrenal
      tuberculosis, or lack of adrenal cytoplasmic antibodies, does not, with
      certainty, differentiate between a tuberculous and idiopathic aetiology. The
      prognosis of Addison's disease was good despite unfavourable circumstances.

PMID- 11242695
TI  - Diagnosis and management of congenital adrenal hyperplasia: clinical, molecular
      and prenatal aspects.
AB  - Congenital adrenal hyperplasia (CAH) is the most common cause of female
      pseudohermaphroditism in Indian children. It is caused by enzymatic defects in
      the steroidogenic pathway of the adrenal glands and is characterized by impaired
      cortisol and aldosterone synthesis and overproduction of androgens. The disease
      usually presents with life-threatening problems and virilization, with long term
      physical and psychological effects. The clinical and laboratory diagnoses play an
      important role in deciding the course of treatment, which continues lifelong. To
      ensure proper growth and development of the patient, optimized disease management
      and treatment with steroids is required. Often the patient also requires surgical
      correction. Recent developments in molecular genetics have greatly helped in
      understanding the pathogenesis of the disease. The gene encoding for steroid 21
      hydroxylase, CYP21, is located on the short arm of chromosome 6 in the HLA region
      and is amplified for genetic diagnosis. Rapid characterization of point mutations
      is possible using the allele-specific polymerase chain reaction technique in
      affected children. Counselling, prenatal diagnosis and treatment are recommended
      in all pregnant women with a positive family history to reduce or eliminate the
      effects in affected foetuses. This spares the female newborn the consequences of
      genital ambiguity and problems of gender identity.

PMID- 11242696
TI  - Maternal thyroid deficiency: is it responsible for a low IQ in the offspring?

PMID- 11242698
TI  - Air pollution: health hazards and policies.

PMID- 11242697
TI  - Nucleic acids in diagnosis.

PMID- 11242699
TI  - Carcinogenicity of asbestos: convincing evidence, conflicting interests.
AB  - In spite of hard epidemiological and clinical evidence associating asbestos fibre
      with asbestosis and cancer, the issue is controversial and likely to remain so.
      The focus is now shifting to non-occupational exposure, differential risk to
      various asbestos fibre types and the relatively low level of carinogenicity of
      the chrysotile form. This creates further space for scientific debate and the
      opportunity to form a considered opinion. However, the situation may take a
      worrisome turn if some of these scientific inquiries are used by market forces to
      their advantage. A look at the history of corporate activities in asbestos
      related research reveals a disturbing trend. Information that was made available,
      through legal interventions, clearly shows how for half a century the asbestos
      industry in collaboration with some academic leaders of occupational medicine
      successfully suppressed evidence against asbestos. In developing countries,
      extensive and aggressive marketing continues by chrysotile producers, mainly
      Canadian companies. There is renewed pressure on this part of the world since new
      use of asbestos has been almost completely discontinued in the developed
      countries as a result of public pressure and state prohibitions. In this
      scenario, relaxation of public health control over any form of asbestos should be
      opposed. It is extremely dangerous and scientifically untenable to say that
      chrysotile asbestos can be used without risk. It has been identified as a potent
      human carcinogen, and remains so. However, some restraint must be exercised while
      dealing with asbestos that has already been released into the environment.
      Disturbing it unnecessarily may cause more harm than good.

PMID- 11242700
TI  - Adverse effects of genetic counselling on women carriers of disease: the Indian
      perspective.

PMID- 11242701
TI  - Medline.

PMID- 11242703
TI  - Have doctors, will deliver super health care.

PMID- 11242702
TI  - Mind your head.

PMID- 11242704
TI  - Myelodysplastic syndrome terminating in leukaemia in spouses.

PMID- 11242705
TI  - Intensive pulse polio immunization workers and vaccine vial monitors.

PMID- 11242706
TI  - Cervical cancer screening: is it a priority among nurses?

PMID- 11242707
TI  - Dr K. V. Desikan gets the Damien-Dutton Award.

PMID- 11242708
TI  - Pre-hospital delay in acute myocardial infarction in an urban Indian hospital: a
      prospective study.
AB  - BACKGROUND: Successful treatment of acute myocardial infarction is dependent on
      early presentation of the patient to the hospital. The factors that contribute to
      delay in seeking treatment have not been systematically evaluated in the Indian
      milieu. METHODS: Patients admitted with acute myocardial infarction to a 125-bed
      urban community hospital were evaluated prospectively. A record of admission
      characteristics, prior medical history, pre-hospital symptoms and treatment
      patterns was completed within 48 hours of each admission. Independent predictors
      of delayed admission were identified by logistic regression. RESULTS: Of 144
      consecutive admissions with myocardial infarction, 133 had completed data as per
      the protocol [mean (SD) age 59 (12.7) years; 79.6% men]. The distribution of
      presentation times was skewed, with the mode, median and mean being 1, 3
      (interquartile range 1.25-11) and 10.9 (SD 20.5) hours, respectively. Seventy
      nine patients (59.4%) consulted a general practitioner prior to hospital referral
      and 48 patients (36.1%) delayed admission to hospital by more than 6 hours from
      the onset of symptoms. On multivariate analysis, individuals who were initially
      seen by a general practitioner (OR 5.57; 95% CI 1.84-16.8) and those over the age
      of 65 years (OR 3.24; 95% CI 1.06-9.89) were identified as 'delayers', while
      patients with severe symptoms (OR 0.32; 95% CI 0.12-0.87) or prodromal angina (OR
      0.25; 95% CI 0.08-0.82) minimized delay. CONCLUSION: Though 50% of patients with
      acute myocardial infarction present to hospital within 3 hours, about 36% delay
      seeking treatment by more than 6 hours. Besides age and the pattern and severity
      of symptoms, visits to the general practitioner were found to be an independent
      correlate of delay.

PMID- 11242709
TI  - Psychiatric disorders in the northern areas of Pakistan.

PMID- 11242710
TI  - Center-based prevalence of anxiety and depression in women of the northern areas
      of Pakistan.
AB  - OBJECTIVE: To estimate the prevalence of anxiety and depression in women of the
      Northern areas. METHODS: A cross-sectional center-based study was conducted at
      Singal Medical Center (SMC), Gilgit, in the Northern Areas of Pakistan, using the
      Hospital Anxiety and Depression Scale (HADS). RESULTS: One hundred and twenty
      women, between the ages of 16 and 60, attended the SMC over a two month period
      and were included in the study. Using HADS, it was found that 50% of the women
      had anxiety and/or depression; 25% suffered only from anxiety, 8% from depression
      and 17% had features of both. CONCLUSION: This study supports the previous
      studies of stress in remote areas and also contradicts the belief that people who
      live in the remote rural areas lead stress-free lives or have low rates of
      psychiatric morbidity (JPMA 50:138, 2000).

PMID- 11242711
TI  - Central nervous system lymphomas: a histologic and immunophenotypic analysis.
AB  - OBJECTIVE: To observe the spectrum of non-Hodgkin's lymphomas involving the
      central nervous system including morphological subtypes and immunophenotypic
      status. SETTING: Retrospective analysis of eleven years (1986 to 1996) data from
      surgical pathology files of Department of Pathology. RESULTS: Forty-three cases
      of non-Hodgkin's lymphomas were diagnosed during the period of eleven years (from
      1986 to 1996), all of which were diffuse types. A total of 1177 Central Nervous
      CNS biopsies were examined, out of which 937 cases were diagnosed as CNS
      neoplasms, the remaining were non-neoplastic in nature. Among 937 CNS neoplasms,
      43 cases (4.6%) were reported as non-Hodgkin's lymphomas. As most of the cases
      were outside referrals, the primary or secondary nature of the lymphomatous
      process could not be assessed. Seventeen cases were intracranial, while 26 cases
      were spinal in location. Majority of the intracranial lymphomas were biopsied
      from the cerebrum (12 cases). Male to female ratio was 1:2. The median age for
      intracranial lymphomas was 50 years and for spinal lymphomas 29 years. There were
      16 cases (37%) of diffuse large cell lymphomas; 7 cases (16%) of diffuse mixed
      small and large cell lymphomas; 3 cases (7%) of diffuse large cell immunoblastic
      lymphomas; 2 cases (4.6%) of lymphoblastic lymphomas and diffuse small non
      cleaved cell lymphomas and one case of small lymphocytic lymphoma and diffuse
      small cleaved cell lymphoma. One case of T cell rich B cell lymphoma was also
      diagnosed in the thoracic spine as primary extranodal lymphoma. Eight cases were
      unclassifiable and in 2 cases the features were suggestive of lymphoma.
      Immunophenotypic analysis was performed in 20 cases, however, in 2 cases the
      results were inconclusive. Fifteen cases (83%) showed immunoreactivity for B cell
      markers and 3 cases showed T cell phenotype out of which one case was
      lymphoblastic lymphoma. CONCLUSION: CNS lymphomas were uncommon tumors and
      comprised 4.6% of the total CNS neoplasms in our study. Moreover, these CNS
      lymphomas accounted for 2.2% of the total non-Hodgkin's lymphomas, including both
      nodal and extranodal. There was a higher incidence of location of these lymphomas
      within the spinal cord than brain. Most of the lymphomas were of intermediate or
      high grade (75%) according to the working formulation. Immunophenotypical status
      revealed B-cell phenotype in 84% of the lymphomas, in which it was tested (JPMA
      50:141, 2000).

PMID- 11242712
TI  - Chemical composition of upper renal tract calculi in Multan.
AB  - OBJECTIVE: To study the chemical composition of upper renal tract (renal and
      ureteric) calculi in Multan. SETTING: Department of Urology, Nishtar Hospital,
      Multan. STUDY PERIOD: September 1992 to February 1999. MATERIAL AND METHODS: A
      total of 700 renal and ureteric calculi were analyzed by chemical method of
      Hodgkinson. RESULTS: The commonest were uric acid (28.1%) calculi, followed in
      frequency by calcium oxalate calculi (26.1%), mixed calculi containing calcium
      oxalate and uric acid (21.8%) and calculi containing calcium oxalate and calcium
      phosphate (10.4%). Other variety of calculi were less common. CONCLUSION: Uric
      acid, calcium oxalate and mixed uric acid and calcium oxalate calculi are the
      main types in Multan region (JPMA 50:145, 2000).

PMID- 11242713
TI  - Effect of Helicobacter pylori density on inflammatory activity in stomach.
AB  - AIM: To assess the relationship of H. pylori density on inflammatory activity in
      different parts of stomach. MATERIALS AND METHODS: Endoscopic biopsies were taken
      from gastric antrum, corpus and cardia of 150 dyspeptic patients in a prospective
      analysis. A semiquantitative scoring was done according to updated Sydney system
      in accordance with the variables like H. pylori density, neutrophil activity and
      mononuclear cell infiltrate. Glandular atrophy and intestinal metaplasia was also
      noted. Statistical analysis was done using Spearman rank correlation test.
      RESULT: One hundred and fifty patients, 94 males and 56 females (with a mean age
      of 35.4) were analyzed. Morphologically within stomach 82.7% of antral, 74% of
      corpus and 68% of cardia biopsies were positive for H. pylori. Correlation
      coefficient of H. pylori density and neutrophil activity was 0.542, 0.644 and
      0.729 for antrum, corpus and cardia respectively (P = 0.00); while the
      correlation coefficient of mononuclear cell infiltrate with H. pylori density was
      0.173, 0.245 and 0.326 for antrum, corpus and cardia respectively (P = 0.035,
      0.003, 0.000). H. Pylori density in corpus and cardia was proportional to its
      density in antrum. CONCLUSION: Density of H. pylori is more in the antrum due to
      its alkaline pH and the neutrophil activity shows a direct association with H.
      pylori density (JPMA 50:148, 2000).

PMID- 11242714
TI  - Effect of acarbose on glycemic control, serum lipids and lipoproteins in type 2
      diabetes.
AB  - OBJECTIVE: To assess the efficacy of acarbose monotherapy during 12-weeks
      treatment on the fasting glycemic level, lipid and lipoproteins profiles, in
      patients with type 2 diabetes mellitus. SETTING: Type 2 diabetics were selected
      from out patient department of Baqai Diabetes and Endocrine Centre, and one other
      diabetic clinic of Karachi, during 1996-97. DESIGN: A prospective intervention
      trial, and a 10 days screening period with a follow-up of 12 weeks. METHODS:
      Forty-four patients (36 men and 8 women, mean age 55.09 +/- 1.72 years) were
      included of whom 25 (56.81%) patients were previously treated with diet alone,
      11(25%) with diet and glibenclamide, 5(11.36%) with diet and gliclazide, and
      3(6.81%) with diet and chlorpropamide, more than at least 3 months known duration
      of diagnosed type 2 diabetes, body mass index (BMI) 23.69 +/- 0.49 kg/m2, were
      insufficiently controlled on diet alone, or diet plus sulfonylureas, were
      studied. The dosage of acarbose was started with 50 mg t.i.d with each meal, if
      necessary, was titrated upward on subsequent visits to 100 mg t.i.d with each
      meal, based on tolerability and efficacy. Fasting blood glucose, lipid and
      lipoprotein profiles were determined at the baseline and at the end of the study.
      RESULTS: Acarbose treatment was associated with significant reduction in fasting
      blood glucose from (mean +/- SE) 173.89 +/- 3.89 mg/dl at day 0 to 161.29 +/-
      3.41 mg/dl at day 90 (P < 0.01). The serum total triglyceride level was (mean +/-
      SE) 188.85 +/- 5.91 mg/dl at entry, and was also significantly decreased to
      158.57 +/- 4.48 mg/dl at day 90, this reduction was found statistically
      significant (P < 0.01). Whereas very-low density lipoprotein cholesterol reduced
      significantly from 33.08 +/- 1.09 mg/dl at day 0 to 31.02 +/- 0.95 mg/dl at day
      90 (P < 0.01). Acarbose had no significant effect on serum total cholesterol, low
      density lipoprotein cholesterol, and High-density lipoprotein cholesterol
      concentrations. Almost, all adverse experiences, as reported by patients on
      acarbose, were related to the digestive system and included diarrhea, flatulence,
      bloating and nausea. Most symptoms were of mild to moderate intensity and tended
      to improve with time. Overall, acarbose was well tolerated and the adverse
      experience profile was clinically acceptable. CONCLUSION: In type 2 diabetic
      patients, acarbose as monotherapy for 12 weeks resulted in beneficial effects on
      glycemic control, fasting blood glucose, mean serum total triglyceride and very
      low density lipoprotein cholesterol decreased significantly. Perhaps attainment
      of normoglycemia on a long-term basis would result in more normal lipid and
      lipoprotein levels. Furthermore use of acarbose can be considered as a useful
      alternative in such type 2 patients, if they are difficult to control with diet
      alone or diet plus sulfonylureas (JPMA 50:152, 2000).

PMID- 11242716
TI  - Trends in nutrition transition: Pakistan in focus.

PMID- 11242715
TI  - Two weeks triple therapy with lansoprazole, amoxycillin and roxythromycin is
      better than dual therapy with lansoprazole and amoxycillin for H. pylori
      infection: a randomised, clinical trial.
AB  - AIMS: To compare the efficacy of 2 weeks of dual therapy of Lansoprazole and
      Amoxycilline with triple therapy of Lansoprazole, Amoxycilline and Roxythromycin
      for H. pylori eradication. SUBJECTS: Twenty-five suffering from dyspepsia and
      found H. pylori positive (CLO) during upper GI endoscopy. METHODS: Patients were
      divided into 2 groups, one group received Lansoprazole (30 mg) once a day, and
      amoxycilline (500 mg) three times a day (group I), while the second group
      received Lansoparazole and amoxycillin in similar dosage with the addition of
      Roxythromycin (150 mg) twice a day (group II). H. pylori status was confirmed on
      endoscopy using CLO test at entry to the protocol and then at 4 weeks. RESULTS:
      H. pylori eradication was 57% in group I and 86% in group II with healing of
      lesions in all cases. CONCLUSION: Better response with triple therapy (group II)
      indicates enhanced eradication of the pathogens with triple therapy while using
      roxythromycin (JPMA 50:157, 2000).

PMID- 11242717
TI  - Lipoma of the bone.

PMID- 11242718
TI  - Research?

PMID- 11242719
TI  - Improving medication safety across a multihospital system.
AB  - BACKGROUND: The Massachusetts Coalition for the Prevention of Medical Errors and
      the Institute for Healthcare Improvement have identified 16 best practices to
      reduce adverse drug events. CareGroup, a network of six hospitals in eastern
      Massachusetts, multiplied its routine use of these best practices tenfold in the
      first 18 months of its medication reliability project. DEVELOPING THE
      COLLABORATIVE STRATEGY: Although CareGroup's long-term plans included
      technological advances such as clinical order entry, computer systems in the
      pharmacy, dispensing stations on patient floors, and bedside bar-coding, efforts
      first focused on manual improvements feasible within a year's time. A 4-year
      strategy involves helping the medication reliability team leaders at each
      hospital to create impressive local results, publicize the results to their
      colleagues, invite their clinical colleagues to learn to use plan-do-study-act
      (PDSA) cycles, and have colleagues lead PDSA cycles themselves. At monthly or
      bimonthly task force meetings, team results are presented and team leaders are
      given specific assignments for their teams. CASE STUDIES: One project reduced the
      time to blood anticoagulation for heparinized patients. The second dramatically
      reduced lookalike/soundalike errors. The third improved the safety of patient
      controlled analgesia. The fourth reduced coumadin incidents. The fifth improved
      the education of patients about their medications. The sixth greatly reduced the
      morning dispensing backlog in the pharmacy. SUCCESS FACTORS: Key success factors,
      in addition to leadership, are the use of data, forcing functions, appropriate
      pacing, inexpensive practices, and a consultant. The pace needed to implement the
      best practices overall made it imperative to make many changes rapidly. Often,
      the team initiated several changes at one time, rather than sequencing changes in
      successive PDSA cycles. LIMITATIONS, BARRIERS, AND NEXT DIRECTIONS: CareGroup
      faces key challenges in measurement and in spreading and deepening the
      involvement of clinicians, particularly physicians. It lacks an overall,
      objective measure of medication safety. Spread of the changes made has been
      incomplete although the adoption of the best practices increased tenfold (from 6
      to 60) in 21 months. Two of the case study interventions--in coumadin order
      sequencing and dedicating a pharmacy technician to order entry--have been
      implemented at only one site to date, even though the adoption of the change
      ideas across hospitals is encouraged. The eventual impact of the changes planned
      for the future, through automated systems such as computerized order entry, is
      much larger. Considerable progress is anticipated in adoption of best practices;
      improvement in top-priority areas of each hospital; improved automation and
      technology in ordering, dispensing, and administering medication; and better
      reporting.

PMID- 11242720
TI  - Developing indicators for emergency medical services (EMS) system evaluation and
      quality improvement: a statewide demonstration and planning project.
AB  - BACKGROUND: The state of California, like every other state, has no system for
      assessing the quality of prehospital emergency medical services (EMS) care. As
      part of a statewide project, a process was designed for the evaluation and
      quality improvement (QI) of EMS in California. Local EMS agency (LEMSA)
      representatives made a commitment to submit data from both the providers and the
      hospitals they work with. INDICATOR SELECTION AND DEVELOPMENT: For conditions
      such as cardiac chest complaints, standardized indicators had already been
      developed, but for many other areas of interest there was either little
      literature or little consensus in the literature. Definitional differences were
      often linked to local-practice protocol differences. A related comparison
      challenge lay in the fact that care protocols may differ across systems. Some
      aspects of care may not be offered at all, which may reflect resource shortages
      or variable medical direction. DATA COLLECTION PROCEDURES: Each indicator was
      precisely defined, and definition sheets and data troubleshooting report forms
      were provided to participants in three data-collection rounds. Participants were
      given 1 month to collect the data, which consisted of summary-level elements (for
      example, average time to defibrillation for all patients 15 years or older who
      received defibrillation in 1998). Data were then aggregated, analyzed, and
      prepared for display in graphs and tables. ACCESS AND MEASUREMENT ISSUES:
      Numerous data collection problems were encountered. For example, not all
      participants could actually access data that they thought would be available.
      Linking data on patients as they travel through the continuum of EMS care
      (dispatch, field, hospital) and linking EMS data to hospital outcomes was also
      difficult. Yet even when data were easily available, challenges arose. The need
      for specificity, the potential misfit between definitions and the available data,
      and the challenges of data retrieval remained salient for the duration of the
      project and made cross-LEMSA and cross-provider comparison problematic.
      RECOMMENDATIONS AND LESSONS LEARNED: The project led to formal policy
      recommendations regarding development of a state-defined minimum data set of
      structure, process, and outcome indicators and their associated data elements;
      provision in the minimum data set for both local-level and statewide indicators;
      and provision of technical assistance at the local-provider level. EPILOGUE:
      Since the project's conclusion in June 2000, many regional and local EMS groups
      have begun to collect data on indicators. Many of the project's recommendations
      have been incorporated into the work plan of the state's System Review and Data
      Committee.

PMID- 11242721
TI  - Comparison of an enhanced versus a written feedback model on the management of
      Medicare inpatients with venous thrombosis.
AB  - BACKGROUND: A multistate randomized study conducted under the Health Care
      Financing Administration's (HCFA's) Health Care Quality Improvement Program
      (HCQIP) offered the opportunity to compare the effect of a written feedback
      intervention (WFI) with that of an enhanced feedback intervention (EFI) on
      improving the anticoagulant management of Medicare beneficiaries who present to
      the hospital with venous thromboembolic disease. METHODS: Twenty-nine hospitals
      in five states were randomly assigned to receive written hospital-specific
      feedback (WFI) of feedback enhanced by the participation of a trained physician,
      quality improvement tools, and an Anticoagulant Management of Venous Thrombosis
      (AMVT) project liaison (EFI). Differences in the performance of five quality
      indicators between baseline and remeasurement were assessed. Quality managers
      were interviewed to determine perceptions of project implementation. RESULTS: No
      significant differences in the change from baseline to remeasurement were found
      between the two intervention groups. Significant improvement in one indicator and
      significant decline in two indicators were found for one or both groups. Yet 59%
      of all quality managers perceived the AMVT project as being successful to very
      successful, and more EFI quality managers perceived success than did WFI managers
      (71% versus 40%). In the majority of EFI hospitals, physician liaisons played an
      important role in project implementation. CONCLUSION: Study results indicated
      that the addition of a physician liaison, quality improvement tools, and a
      project liaison did not provide incremental value to hospital-specific feedback
      for improving quality of care. Future studies with larger sample sizes, lengthier
      follow-up periods, and interventions that include more of the elements shown to
      affect practice behavior change are needed to identify an optimal feedback model
      for use by external quality management organizations.

PMID- 11242722
TI  - Beyond structure-process-outcome: Donabedian's seven pillars and eleven
      buttresses of quality.

PMID- 11242723
TI  - Comparison of topical EMLA 5% oral adhesive to benzocaine 20% on the pain
      experienced during palatal anesthetic infiltration in children.
AB  - PURPOSE: The purpose of this investigation was to compare the pain responses of
      children during local anesthetic infiltration at bilateral palatal sites prepared
      with the topical application of benzocaine 20% oral adhesive (Orabase-B) versus
      benzocaine 20% gel (Hurricaine) or EMLA 5% oral adhesive (EMLA 5% cream in
      Orabase Plain). METHODS: Forty subjects, aged 7-15 years old, received bilateral
      palatal injections following topical application of anesthetic agents applied in
      a randomized, crossover design. Pain responses were compared based upon subject
      self-report using a visual analogue scale (VAS), changes in the subject's heart
      rate, and operator assessment using a modified Children's Hospital of Eastern
      Ontario Pain Scale (CPS) that rated behavioral changes in children. Following the
      injections, the subjects were asked to choose which agent was preferred based on
      comfort and taste acceptance. RESULTS: All the agents tested were equivalent in
      injection pain response comparisons, but Hurricaine had a slight advantage in
      expressed subject preference and taste acceptance over the other topical
      anesthetic agents tested. CONCLUSIONS: The selection of EMLA 5% oral adhesive
      over other commercially available products containing benzocaine 20% is not
      recommended for palatal site preparation in children. The lack of demonstrated
      superiority in efficacy and subject preference, the necessity to custom mix the
      cream into an oral adhesive paste, the extended duration of time required for
      onset of action, the greater potential for complications associated with systemic
      absorption, and product cost preclude the use of EMLA 5% oral adhesive as an
      intraoral topical anesthetic agent.

PMID- 11242724
TI  - Mineral trioxide aggregate vs. formocresol in pulpotomized primary molars: a
      preliminary report.
AB  - PURPOSE: The aim of this study was to compare the effect of mineral trioxide
      aggregate (MTA) to that of formocresol (FC) as pulp dressing agents in
      pulpotomized primary molars with carious pulp exposure. METHODS: Forty-five
      primary molars of 26 children were treated by a conventional pulpotomy technique.
      The teeth were randomly assigned to the MTA (experimental) or FC (control) group
      by a toss of a coin. Following removal of the coronal pulp and hemostasis the
      pulp stumps were covered with an MTA paste in the experimental group. In the
      control group, FC was placed with a cotton pellet over the pulp stumps for 5
      minutes and removed; the pulp stumps were then covered by zinc oxide-eugenol
      (ZOE) paste. The teeth of both groups were restored with stainless steel crowns.
      Eighteen children with 32 teeth arrived for clinical and radiographic follow-up
      evaluation ranging from 6 to 30 months. RESULTS: The follow-up evaluations
      revealed only one failure (internal resorption detected at a 17 months
      postoperative evaluation) in a molar treated with formocresol. None of the MTA
      treated teeth showed any clinical or radiographic pathology. Pulp canal
      obliteration was observed in 9 of 32 (28%) evaluated molars. This finding was
      detected in 2 out of the 15 teeth treated with FC (13%) and in 7 out of the 17
      treated with MTA (41%). CONCLUSION: MTA showed clinical and radiographic success
      as a dressing material following pulpotomy in primary teeth and seems to be a
      suitable replacement for formocresol in primary teeth.

PMID- 11242726
TI  - Compomers as Class II restorations in primary molars.
AB  - A variety of alternatives to amalgam are now available for use in class II
      restorations in primary teeth, including glass ionomer, composites, and
      intermediate materials such as compomer and resin modified glass ionomers (RMGI).
      The purpose of the present study was to evaluate the clinical performance of two
      compomers, Hytac and Dyract, and to compare these results to those reported for
      other intracoronal restorative materials. Evaluation after 24 months shows Hytac
      and Dyract to have performed well and comparably as class II restorations in
      primary teeth. The low failure rate, even in a population with a high caries
      increment, suggests that compomers are a suitable alternative to amalgam or
      other, tooth-colored materials when used as class II restorations in primary
      teeth.

PMID- 11242725
TI  - Reducing children's injection pain: lidocaine patches versus topical benzocaine
      gel.
AB  - PURPOSE: The purpose of this study was to compare the effectiveness of lidocaine
      patches and topical anesthetic gel in reducing injection pain in children.
      METHODS: Thirty-two children received bilateral greater palatine injections of
      0.2 cc of 2% lidocaine with 1:100,000 epinephrine at the same visit. Injections
      followed a 15 minute application of DentiPatch (20% lidocaine) or a 1 minute
      application of topical anesthetic gel (Topex, 20% benzocaine). Each child
      completed a Faces Pain Scale and Visual Analog Scale after each injection and was
      asked which injection hurt more. Injections were videotaped and two independent
      evaluators, using the Sounds, Eyes, and Motor Scale, rated observed pain-related
      behavior. Inter-rater reliability was established at 96%. RESULTS: A significant
      difference was shown in observed pain-sounds favoring use of the DentiPatch (P <
      .003, Wilcoxon Sign Rank Test). Using Wilcoxon Sign Rank Test and paired t-tests,
      no significant differences were shown in either reported pain or observed pain
      motor. CONCLUSIONS: A statistically significant decrease in observed verbal
      indicators of injection pain was found when the DentiPatch was used 20%: compared
      to a 1 minute application of topical anesthetic gel. However, no significant
      difference was found between the two study groups in either reported pain or
      observed pain-motor responses.

PMID- 11242727
TI  - Clinical evaluation of and parental satisfaction with resin-faced stainless steel
      crowns.
AB  - PURPOSE: This study evaluated the clinical success and parental acceptance of
      anterior primary dentition caries treatment with prefabricated resin-faced
      stainless steel crowns. METHODS: A retrospective analysis of maxillary anterior
      primary dentition caries treatment using Whiter Biter II Crowns was performed.
      Each crown was evaluated for retention, fracture, interface failure, color match,
      marginal integrity, and surface texture. Parental satisfaction regarding the
      esthetics of the crowns was evaluated by survey. RESULTS: Thirty-eight crowns
      were evaluated in 12 children. The average crown age at time of examination was
      20.7 months. Three teeth were lost to trauma with all other crowns remaining
      intact. Twelve crowns (32%) showed loss of at least some facial resin. Nine
      crowns (24%) had complete loss of the resin facing. Overall parental satisfaction
      with the treatment was excellent, however, satisfaction with crown esthetics
      received the lowest rating. CONCLUSIONS: While parental satisfaction with
      treatment of anterior primary dentition caries with prefabricated resin-faced
      stainless steel crowns is excellent, the high failure rate of the resin facings
      is problematic.

PMID- 11242728
TI  - Prevalence of enamel hypoplasia and isolated opacities in the primary dentition.
AB  - PURPOSE: Enamel hypoplasia is of interest to both the clinician and the basic
      scientist because it may indicate an increased risk for caries and can contribute
      to the understanding of enamel development. The purpose of this paper is to
      report the prevalence of enamel hypoplasia and isolated enamel opacities in a
      cohort of healthy, well-nourished children in Iowa. METHODS: The study sample
      consisted of 698 children examined at 4-5 years of age. Individual tooth surfaces
      were scored for the presence of enamel hypoplasia (EH) and isolated enamel
      opacities. Prevalence of EH and isolated opacities were determined by tooth type
      and by gender. RESULTS: Six percent of the children examined had at least one
      tooth with EH; 27% had at least one tooth with isolated enamel opacities. There
      was no difference in the prevalence of EH between boys and girls, but
      significantly more boys than girls had enamel opacities. CONCLUSIONS: The
      prevalence of enamel defects in this study group is comparable to that seen in
      other studies of normally developed children except that in this study, the
      primary tooth types most commonly affected with enamel hypoplasia or isolated
      opacities were mandibular second molars and maxillary second molars,
      respectively.

PMID- 11242730
TI  - Recertification--it's about time.

PMID- 11242729
TI  - Dental erosion in children: a literature review.
AB  - Epidemiological studies have shown that the prevalence of dental erosion in
      children varies widely between 2 and 57%. Changes seen in dental erosion range
      from removal of surface characteristics to extensive loss of tooth tissue with
      pulp exposure and abscess formation. Symptoms of dental erosion range from
      sensitivity to severe pain associated with pulp exposure. The etiology of dental
      erosion is dependent on the presence of extrinsic or intrinsic acid in the oral
      environment. Extrinsic sources of acids in children include frequent consumption
      of acidic foods and drinks, and acidic medications. Regurgitation of gastric
      contents into the mouth, as occurs in gastroesophageal reflux, is the most common
      source of intrinsic acid in children. A multitude of factors may modify the
      erosion process, such as saliva, oral hygiene practices, and presence or absence
      of fluoride. When dental erosion is diagnosed, it is important to investigate and
      identify the acid source, and to determine if the process is ongoing. The aim of
      treatment is to eliminate the cause of acid exposure, and to minimize the effects
      of acid exposure where it is not possible to remove the acid source. Restoration
      of the dentition involves stainless steel crowns to restore lost vertical
      dimension, and composite resin for esthetics.

PMID- 11242731
TI  - Prevalence of orodental findings in HIV-infected Romanian children.
AB  - BACKGROUND: Romania, the pediatric AIDS capital of the world, has tremendous
      unmet dental care needs for children and adolescents with HIV infection. The
      purpose of this study was to assess the prevalence of orodental conditions in
      symptomatic HIV-positive children from Constanta, Romania. METHODS: The children
      underwent dental examinations and treatment at Constanta Municipal Hospital by a
      volunteer team of dental healthcare professionals from the United States. Oral
      lesions and dental caries were recorded during an 8-day period prior to
      initiating comprehensive dental care. RESULTS: The study population consisted of
      173 children (88 males; 85 females) with a mean age of 8.8 years (range 6 to 12
      years). The primary HIV risk factor was contaminated needle reuse and/or blood
      products (88%). The most common oral and perioral lesions included: candidiasis
      (29%), ulcers (15%), salivary gland disease (9%), necrotizing ulcerative
      gingivitis/periodontitis (5%), linear gingival erythema (4%), labial molluscum
      contagiosum (3%), oral warts (2%), hairy leukoplakia (2%), and herpes zoster
      (1%). One or more oral/perioral lesions occurred in 55% of the children. Severe
      dental caries was noted in the majority of children (dfs/dft 16.9/3.7 and
      DMFS/DMFT 8.1/3.1). Over-retention of primary teeth (25%) and delayed eruption
      (42%) were common. Postoperative complications included delayed clotting (common)
      and thrombocytopenia-induced bleeding disorders (4%). CONCLUSIONS: The oral
      healthcare needs of Romanian HIV-infected children are considerable, with the
      majority living with persistent, symptomatic oral disease.

PMID- 11242732
TI  - The relationship between child temperament and early childhood caries.
AB  - PURPOSE: Among the potential risk factors associated with nursing caries/baby
      bottle tooth decay--a subset of Early Childhood Caries (ECC)--is a "strong
      tempered" behavioral style in the child. However, the few empirical studies that
      have investigated this description remain controversial. The research goal of
      this study was to operationalize the "strong-tempered" profile and investigate
      its association to parental feeding practices and ECC levels. METHODS: In an
      observational-correlational study design, 58 children (ASA I), ages 18 to 70
      months (M = 43 months, SD = 17), were reliably assessed for ECC levels by a
      clinical evaluator. A second evaluator, blind to ECC status, interviewed parents
      using a demographic survey, a feeding practices measure, and the EAS Temperament
      Survey for Children. RESULTS: Multiple regression analyses indicated that none of
      the four temperament factors (Emotionality, Activity, Sociability, and Shyness)
      significantly predicted duration of feeding habit defined as the length of time
      in months that the child breast or bottle fed, whichever lasted the longest.
      However, the combination of greater duration of feeding habit and higher levels
      of Shyness predicted all three measures of ECC: the presence or absence of caries
      (r2 = .19, P < .001), the number of carious teeth (r2 = .23, P < .001) and the
      number of carious surfaces (r2 = .21, P < .001). Furthermore, the addition of
      Native status significantly increased the predictive value of all of three models
      (r2 = .37, r2 = .43, r2 = .29, respectively, Ps < .0001). CONCLUSION: Temperament
      did not predict the duration of feeding habit but together, shyness and duration
      of feeding habit was associated with ECC.

PMID- 11242733
TI  - Are general dentists' practice patterns and attitudes about treating Medicaid
      enrolled preschool age children related to dental school training?
AB  - PURPOSE: The purpose of this study were to investigate the willingness of general
      practitioners to provide dental care for preschool-aged children, and to explore
      the relationship between dental school experiences and practitioners' attitudes
      about treating Medicaid-enrolled children 3 years of age and younger. METHODS: A
      survey was mailed to 3,559 randomly selected general dentists in Texas.
      Respondents were asked to answer questions about their willingness to provide
      specified dental procedures for children of different ages, their dental school
      experiences with pediatric dentistry and whether these experiences were hands-on,
      lecture or no training, and their attitudes concerning treating Medicaid-enrolled
      children 3 years of age or younger. Associations between attitudes about treating
      Medicaid-enrolled children and dental school experiences were determined.
      RESULTS: The response rate was 26%. Almost all respondents were willing to
      provide routine procedures such as an examination (95%) and prophylaxis (94%) for
      children 5 years or younger. However, as children became younger and procedures
      more difficult, the number of general dentists willing to provide treatment
      decreased. The level of dental school training was significantly associated with
      the attitudes of general dentists about providing dental care for Medicaid
      enrolled preschool-aged children (P < or = 0.05). CONCLUSION: Identification of
      factors associated with general dentists' willingness to see young children may
      improve access by increasing the number who will provide care for preschool-aged
      children.

PMID- 11242734
TI  - Social factors associated with pediatric emergency department visits for caries
      related dental pain.
AB  - PURPOSE: This study was performed to describe and relate sociodemographic factors
      and management of visits to a pediatric hospital emergency department for caries
      related dental pain. METHODS: Retrospective chart review of cases with a
      verifiable chief complaint of caries-related dental pain in 1998, was conducted
      using established protocol and trained reviewers. RESULTS: Three hundred of 984
      hospital ED dental emergencies met the study's selection criteria and 109
      children were six years old or younger. Almost two-thirds (66%) came from single
      parent families. Fifty-eight percent were self-pay or covered by government
      programs and the rest had some insurance. African-American children were 45% of
      cases. Over 80% were from within Franklin County, OH. Only 4 children (1%) had
      been seen for the same tooth previously. Lower primary molars were most often
      affected. Race, insurance, parental marital status were not significantly related
      to follow-up attendance at the facility (P > 0.05). Those living outside Franklin
      County and under 5 years of age were more likely to attend follow-up appointments
      (P < 0.05). When compared to the catchment population of Franklin County, this ED
      sample had six times as many uninsured children, two and a half times more
      African-Americans, and came from single parent families four and a half times
      more often. CONCLUSIONS: Children seen in the ED were predominantly poor, from
      single-parent families, and disproportionately minority, and were different from
      the catchment area population. These social risk factors were not related to
      attendance at follow-up.

PMID- 11242735
TI  - Radiographic assessment of the alveolar bone height in children and adolescents
      with familial dysautonomia.
AB  - PURPOSE: Familial dysautonomia (FD) is a progressive neuropathy, characterized by
      somatic and skeletal abnormalities, and by a variety of oral and diet
      disturbances. The purpose of the study was to assess the alveolar bone height at
      the molar areas of children and adolescents with FD. METHODS: The distance from
      the cemento-enamel junction (CEJ) to the alveolar bone crest (ABC) was measured
      on routine diagnostic bitewing radiographs of nine males and seven females with
      FD (mean age = 122 months) and in those of two matching groups (C1 = 119 months;
      C2 = 122 months). RESULTS: The mean values for the maxilla were significantly
      larger than those in the mandible. A positive significant correlation was found
      between the CEJ-ABC measurements of the primary and the permanent teeth, and
      between the CEJ-ABC measurements and age. The mean values per patient for the CEJ
      ABC distances of the FD group were smaller than the control groups, but the
      difference was not statistically significant. The CEJ-ABC measurements in the
      primary and the permanent molars were smaller in the FD group, and in the
      premolars and permanent cuspids they were larger than those in the two control
      groups. These differences were not statistically significant. No differences were
      found between the FD and the control groups in the primary cuspids. CONCLUSIONS:
      The alveolar bone height of children and adolescent with familial dysautonomia
      does not differ from that of healthy controls.

PMID- 11242736
TI  - Economic implications of evidence-based caries prevention in pediatric dental
      practice: a model-based approach.
AB  - OBJECTIVES: This paper presents an economic model which can be used to assess the
      potential implications of evidence-based caries prevention in pediatric dental
      practice. METHODS: Assessment of the evidence indicated that most children in the
      United States were likely to experience dental caries, though the severity of the
      disease would be minimal in most of them. Based on the evidence, it was concluded
      that annual recall examination and topical fluoride application would suffice as
      the norm for caries prevention. A model was developed to estimate the extent and
      cost of caries prevention in a traditional and an evidence-based pediatric dental
      practice. RESULTS: The model showed that evidence-based caries prevention
      resulted in a one-third decline in the number of recall examination visits
      provided, while the ensuing patient revenues from recall appointments declined by
      two-thirds in a calendar year. CONCLUSIONS: Evidence-based caries prevention will
      likely result in a significant decline in preventive services revenues and create
      additional capacity in pediatric dental practices. This economic impact will
      likely be absorbed by the current undersupply of pediatric dentists and by the
      reformulation of practice revenue streams.

PMID- 11242737
TI  - Acceptance of the xylitol chewing gum regimen by preschool children and teachers
      in a Head Start program: a pilot study.
AB  - PURPOSE: This pilot study evaluated the acceptance and compliance of a xylitol
      chewing gum regimen by both children and classroom teachers in a Head Start
      program. METHODS: Thirty-five children chewed 100% xylitol gum (XyliFresh 100%,
      Leaf, Inc., 500 Field Dr., Lake Forest, IL 60045 U.S.A.) three times a day over a
      three week period. Children's acceptance was evaluated using a picture selection
      test. Teachers' acceptance was evaluated using a questionnaire. The children's
      and teachers' compliance was evaluated using a daily checklist that was completed
      by each teacher. RESULTS: Positive ratings were given for xylitol gum chewing
      (94%) and for taste (86%). Children's acceptance and compliance for chewing was
      excellent. Children chewed the gum at designated times and none of the children
      swallowed the gum. Teachers' acceptance of the chewing program was low. Three out
      of five participating teachers thought the gum chewing disturbed the classroom
      routine and four were not willing to participate in the program next year.
      Teachers' compliance was good and they followed by instructions during a three
      week period. CONCLUSIONS: This study supports the suggestion that chewing xylitol
      gum is well accepted by children. Collaboration and education is essential to
      motivate teachers to adopt and supervise school-based prevention programs.

PMID- 11242738
TI  - Liver transplantation: current status and future prospects.
AB  - The enormous progress that has been made in liver transplantation over the past
      two decades has culminated in survival approaching 90% at 12 months. The success
      of the procedure combined with the widening spectrum of disease processes deemed
      amenable to liver transplantation has meant that there are too few donors for
      those awaiting transplantation. This has extrapolated to many patients having
      such advanced disease by the time a suitable donor liver is available, that they
      are almost non-transplantable. The immediate options facing the transplant
      community are to decrease the number of patients listed or to increase the number
      of living donor transplants. Alternatives to liver transplantation such as
      hepatocyte transplantation, gene therapy, xenotransplantation and the
      bioartificial liver are being sought but, at best, are some way from clinical
      application. It is anticipated that a number of liver diseases that are
      indications for liver transplantation at this time will have progression arrested
      or will be cured by medical therapy in the future.

PMID- 11242739
TI  - Restorative proctocolectomy.
AB  - The development and refinement of pelvic pouch surgery now allows the excision of
      a diseased colon while maintaining transanal faecal continence. The success of
      restorative proctocolectomy is largely dependent on careful patient selection
      combined with meticulous surgical technique. The authors discuss the main
      indications for restorative proctocolectomy and describe the surgical procedure.

PMID- 11242740
TI  - Altered cardiac function.
AB  - An understanding of the normal functioning of the heart and how it fails is
      important since it allows rational treatment. Pre-existing cardiac disease and
      myocardial dysfunction is common in the surgical patient. Moreover, the stress
      response of surgery and the alterations in body physiology seen in the post
      operative period may further aggrivate any cardiac compromise. The end result may
      be a patient who has cold peripheries due to vasoconstriction and hypoperfusion
      with dyspnoea due to congested lungs and a heart that cannot function adequately.
      The postoperative patient is at risk of these changes because of the stress
      response, analgesic therapy, inappropriate fluid management, hypoxia and previous
      cardiac compromise. The patient with sepsis is at further risk because of
      alterations in both systolic and diastolic function, which may be the result of
      inadequate fluid resuscitation and also release of a variety of inflammatory
      mediators. Until treatments, which are aimed at correcting the effects of these
      mediators, are proven to be beneficial then the septic patient will continue to
      be managed according to the physiological principles as outlined by Starling.

PMID- 11242741
TI  - Long-term results of surgical decompression of thoracic outlet compression
      syndrome.
AB  - BACKGROUND: Thoracic outlet compression syndrome is characterised by a variety of
      symptoms relating to compression of the neurovascular bundle. Though no one test
      is specific for the syndrome, relief of symptoms may be obtained following
      surgery in up to 99% of cases. PATIENTS AND METHODS: The notes of 118 patients
      operated on in 126 operations by a single surgeon using a supraclavicular
      approach were reviewed. Symptoms, pre-operative investigations, and complications
      were all documented. Outcome at 6 weeks, 6, 12 and 24 months follow-up was also
      recorded. In addition, 61 patients were contacted by telephone, in order to
      assess current level of symptoms. RESULTS: Symptoms were predominantly motor,
      sensory or vasomotor, and were present for a mean of 19.6 months prior to
      surgery. Complications were rare, but included a pneumothorax requiring a chest
      drain (n = 1) and infraclavicular anaesthesia (n = 13). The mean duration of
      hospital stay was 2.1 days. At 6 weeks follow up, 86.5% of patients reported
      either an improvement, or complete resolution of their symptoms. Sixty-one
      patients were contactable, a mean of 55 months following decompression. Of these,
      44 (72.1%) were either improved or asymptomatic. CONCLUSION: Decompression for
      thoracic outlet compression syndrome through a supraclavicular approach
      encompassing first rib resection leads to good long-term results with few
      complications.

PMID- 11242742
TI  - Repair of incisional hernias.
AB  - Incisional hernias develop in up to 11% of surgical abdominal wounds with a
      possible recurrence following repair of 44%. We describe our experience with a
      combined fascial and prosthetic mesh repair. Thirty-five patients (16M:19F) have
      been treated. The original operation was bowel related in 19 cases,
      gynaecological in 8, hepatopancreaticobiliary in 3 patients, aortic aneurysm
      repair in 2 and involved a thoraco-laparotomy in 3. The incisions were midline in
      26 cases, transverse in 6, paramedian in 2 and rooftop in one patient. The
      hernias were considered subjectively to be large in 15, medium in 14 and small in
      6 of the patients. A proforma was completed for each patient noting intra
      operative and post-operative complications, post-operative hospital stay and
      analgesic requirements. Post-operative complications included seroma formation in
      6 patients, deep vein thrombosis in one and a non-fatal pulmonary embolism in
      another. One patient developed a wound haematoma and one had a superficial wound
      infection. Post-operative in-hospital stay ranged from 1 to 27 days with a mean
      of 6.2 days. Of the 35 patients 33 were available for follow-up. Follow-up was
      for a median of 20.3 months (range 6.0 to 54.1 months). Two of these (6%)
      patients reported a persistent lump and one (3%) reported persistent pain but
      none of the remaining 33 was found to have a recurrence. We advocate this
      technique because it is applicable to all hernias, most of the mesh is behind the
      rectus sheath and has 2 points of fixation, it is relatively pain-free allowing
      early mobilisation, has a modest complication rate and a low recurrence rate.

PMID- 11242743
TI  - Frederick Knox, younger brother and assistant of Dr Robert Knox: his contribution
      to "Knox's Catalogues".
AB  - Analysis of the material written in the two manuscript volumes known as the "Old"
      and "New" Knox Catalogues has revealed that most of their contents are in the
      hand of Frederick Knox, younger brother of Dr Robert Knox. Frederick was employed
      by Dr Knox as his research assistant, and prepared detailed lists of the items in
      his brother's museum collection. He also dissected and prepared human and non
      human specimens, many of which were described by Dr Knox in his numerous
      publications. As relatively little is known about Frederick Knox, this seemed a
      timely opportunity to evaluate his contribution to Knox's anatomy class in the
      extra-mural school. When in due course Dr Knox's success as a teacher of anatomy
      gradually declined, he decided to leave Edinburgh to pursue his career in London.
      It was at about this time that his brother Frederick also decided to leave
      Edinburgh to establish a new career for himself in the Antipodes. The present
      whereabouts of the majority of Knox's enormous teaching collection of anatomical
      preparations and his comparative anatomy collection are unknown, and suggestions
      are made as to their possible whereabouts.

PMID- 11242744
TI  - Congenital aplasia or hypoplasia of extensor tendons of the hand--a case report
      and review of the literature.
AB  - An 8-year-old boy presented with inability to extend his fingers. Examination
      revealed congenital hypoplasia of the extensor tendons. He was treated with
      tendon transfers. We present a review of the literature and management of such
      cases.

PMID- 11242745
TI  - A modified technique of Veress needle insertion in laparoscopic surgery.

PMID- 11242746
TI  - Methods for achieving pneumoperitoneum at laparoscopy. 1999; 44(4):324-7.

PMID- 11242747
TI  - Renal cell carcinoma: incidental detection and pathological staging. 2000;
      45(5):291-295.

PMID- 11242748
TI  - Cardiothoracic trainees and junior doctors' working hours.

PMID- 11242749
TI  - Dendritic cells (I): Biological functions.
AB  - Dendritic cells (DCs) are potent antigen presenting cells (APCs) that possess the
      ability to stimulate naive T cells. They comprise a system of leukocytes widely
      distributed in all tissues, especially in those that provide an environmental
      interface. DCs posses a heterogeneous haemopoietic lineage, in that subsets from
      different tissues have been shown to posses a differential morphology, phenotype
      and function. The ability to stimulate naive T cell proliferation appears to be
      shared between these various DC subsets. It has been suggested that the so-called
      myeloid and lymphoid-derived subsets of DCs perform specific stimulatory or
      tolerogenic function, respectively. DCs are derived from bone marrow progenitors
      and circulate in the blood as immature precursors prior to migration into
      peripheral tissues. Within different tissues, DCs differentiate and become active
      in the taking up and processing of antigens (Ags), and their subsequent
      presentation on the cell surface linked to major histocompatibility (MHC)
      molecules. Upon appropriate stimulation, DCs undergo further maturation and
      migrate to secondary lymphoid tissues where they present Ag to T cells and induce
      an immune response. DCs are receiving increasing scientific and clinical interest
      due to their key role in anti-cancer host responses and potential use as
      biological adjuvants in tumour vaccines, as well as their involvement in the
      immunobiology of tolerance and autoimmunity.

PMID- 11242750
TI  - The traumatic brain injury program's project: BRAIN.

PMID- 11242751
TI  - AMA, TMA analyzing new privacy rules for medical records.

PMID- 11242752
TI  - From strategy to survival--TMA's future takes shape.

PMID- 11242754
TI  - Why is health policy so hard to make?

PMID- 11242753
TI  - The disaster of a suspected coverup.

PMID- 11242755
TI  - Cat bites: a source of rabies exposure in rural Tennessee.
AB  - In summary, several errors occurred with this patient. One, the patient should
      have been treated prophylactically for P. multocida, as most cat bites become
      infected. In the patient not allergic to penicillin, augmentin is the drug of
      choice, not erythromycin. Two, rabies postexposure prophylaxis should have been
      advised immediately after assessing the significance of the exposure. A feral cat
      must be assumed to be rabid if it cannot be quarantined for 10 days. Therefore,
      the bite or scratch from such an animal constitutes a significant rabies
      exposure. Three, initial postexposure rabies prophylaxis must include both HRIG
      and the first of a series of either HDCV, RVA, or PCEC.

PMID- 11242756
TI  - Cat cuddler's cough.
AB  - Pasteurella multocida typically causes cutaneous infections in humans following
      animal bites or scratches. Primary pulmonary disease, however, can occur in
      humans after inhalation of airborne particles or by aspiration of colonized or
      infected nasopharyngeal secretions containing this organism. Symptoms of P.
      multocida pulmonary infection in humans are variable, ranging from cough with or
      without hemoptysis to severe prostration. P. multocida infection of the lower
      respiratory tree has a predilection for elderly patients with underlying lung
      pathology, especially chronic obstructive pulmonary disease and bronchiectasis.
      This report reminds the clinician that P. multocida can cause pulmonary infection
      in patients without underlying lung disease, and stresses the importance of
      careful history when presented with an indolent infection.

PMID- 11242757
TI  - [Pneumococcal antibiotic resistance. Data from 6 regional registries for 1999].
AB  - RESISTANCE BY REGION: Resistance varied greatly by region, ranging from 34.2%
      resistant strains in Alsace to 63.1% in Brittany. The incidence of resistant
      strains was always higher in children (especially in children aged 1 to 5 years)
      and in ENT samples. The time course of resistance has varied between regions, as
      has that of serotypes. CRUCIAL FINDING: In these 6 regions, and despite a high
      incidence (that varied from one region to another) of reduced susceptibility
      strains for penicillin G, amoxicillin (19-32%) and cefotaxime (6.5-18.5%),
      amoxicillin-cefotaxime resistant strains remained very rare (0.2-3.5%).

PMID- 11242758
TI  - [Pneumococcal resistance].

PMID- 11242759
TI  - [Haemophilus influenzae sensitivity to beta-lactamines].
AB  - FACTS: Among the 280 strains studied, 106 were sensitive to beta-lactams, 92 were
      beta-lactamase producers, and 82 non-producers of beta-lactamase had reduced
      sensitivity to beta-lactams. QUESTION: The results of this study illustrate the
      complexity of characterizing the phenotypic resistance of H. influenzae and
      raises the question of which in vitro susceptibility tests best identify
      resistance.

PMID- 11242761
TI  - [Beta-lactamase production in Prevotella and in vitro sensitivity to beta
      lactamines].
AB  - FREQUENCY OF BETA-LACTAMASE ACTIVITY: Prevotella spp. are anaerobic pathogenic
      bacteria. Among 100 strains isolated, beta-lactamase producing strains accounted
      for 58%. Fifty-two percent of the strains were pigmented and 63% were non
      pigmented. ACTIVITY AGAINST BETA-LACTAMASE PRODUCERS: In general, all the
      antibiotics exhibited higher activity against non producers than against beta
      lactamase producers. Minimum inhibitory concentrations for amoxicillin/davulanic
      acid was lower or equal to 2 mg/l for all strains isolated.

PMID- 11242760
TI  - [Haemophilus influenzae sensitivity to beta-lactamines].

PMID- 11242762
TI  - [Prevotella and its sensitivity to beta-lactamines].

PMID- 11242764
TI  - [Pneumococcal antibiotic resistance in 1999. Results from 19 registries for
      1999].
AB  - BETA-LACTAM RESISTANCE: Among the 9956 strains of Streptococcus pneumoniae
      isolated in adults, 39% had some degree of penicillin resistance (reduced
      susceptibility), but there were relatively few strains highly resistant to
      penicillin: 10%. Among the 4422 strains isolated in children, the overall rate of
      penicillin resistance was higher (51%) with 15% highly resistant strains. For
      amoxicillin, the rate of reduced susceptibility was 25% while 1.4% were
      amoxicillin-resistant. For ceftaxime the respective figures were 21% and 0.3%
      OTHER ANTIBIOTIC FAMILIES: Important reduction in the susceptibility of all
      strains, more pronounced for peni-R strains, for macrolides, cotrimoxazole,
      tetracyxine and chloramphenicol. Very rare resistance to rifampicin and intact
      susceptibility to vancomycin. CHILDREN VERSUS ADULTS: The rate of reduced
      susceptibility to beta-lactams was higher in children: 31% versus 23% for
      amoxicillin and 21% versus 14% for cefotaxime. However there were only a few rare
      strains that were amoxicillin and cefotaxime resistant. Unlike what was observed
      in adults, there were major differences by site of sampling; strains isolated
      from purulent middle ear fluid exhibited the strongest resistance.

PMID- 11242765
TI  - [Pneumococcal antibiotic resistance. Results from 21 regional registries for
      1999].
AB  - IN ADULTS: The prevalence of reduced susceptibility to penicillin was an
      estimated 40% with rates of 23% for amoxicillin and 15% for cefotaxime. For
      resistant strains, the rates were 11% for penicillin, 1.3% for amoxicillin and
      0.3% for cefotaxime. For respiratory tract samples grouped together, pneumococcal
      resistance to antibiotics, erythromycin excepted, has increased little in France
      since 1997. For lung samples, beta-lactam activity has remained stable with only
      rare strains exhibiting amoxicillin and cefotaxime resistance. IN CHILDREN: The
      prevalence of reduced susceptibility to penicillin was 53%, 32% for amoxicillin
      and 22% for cefotaxime. Despite a high rate of penicillin-G resistant strains
      (16%), amoxicillin and cefotaxime resistant strains remain rare, 2.8% and 1.2%
      respectively. For all samples grouped together, pneumococcal resistance to
      antibiotics, erythromycin excepted, has increased little in France since 1997.
      There has however been an alarming rise in resistance of strains isolated from
      blood cultures. Globally, beta-lactam activity has remained stable and only rare
      amoxicillin and cefotaxime resistant strains have been isolated, including middle
      ear fluid sample. SEROTYPE DISTRIBUTION: Among the strains with reduced
      susceptibility to penicillin isolated in 1999, the more frequent serotypes were
      serotypes 6, 9, 14, 15, 19 or 23.

PMID- 11242766
TI  - [Why a scientific medical journal in the French language?].

PMID- 11242768
TI  - [Progressive hemifacial atrophy in the young patient: surgical problems in
      children].
AB  - Parry-Romberg syndrome is characterized by a limited progressive hemifacial
      atrophy. For young patients, the surgeon has to deal with two tendencies: the
      patient's growth and the course of the syndrome. When managing such an
      unpredictable disease, the surgeon has to make a guess about the future course of
      the structural movements. We reviewed our experience and analyzed the different
      surgical possibilities for reconstructive surgery for Parry-Romberg syndrome.

PMID- 11242767
TI  - [Progressive hemifacial atrophy in the young patient: physiopathologic
      hypotheses, diagnosis and therapy].
AB  - Parry-Romberg syndrome is characterized by a limited progressive hemifacial
      atrophy. Since its first description in 1825, this syndrome has aroused
      interrogation and reflection about is pathophysiology, its variable clinical
      expression and its progression. The first part of this focuses on the different
      hypotheses advanced to date to explain this type of atrophy. We then recall the
      different steps for clinical diagnosis and treatment. Management of such an
      unpredictable disorder is particularly difficult. Because of the uncertain
      pathophysiology, medical therapy has not been very successful. Palliative
      reconstruction surgery remains the only possibility. We present three cases
      illustrating this review of progressive hemifacial atrophy.

PMID- 11242769
TI  - [Pre-implantation iliac graft in the sinus. Retrospective study of the
      complications encountered in 100 cases].
AB  - MATERIAL AND METHODS: This series included 60 patients operated on between 1996
      and 1998. Preoperative work-up included a x-ray study bone quality, preparation
      of the buccal cavity and assessment of the rhinosinus. We used the surgical
      technique described by Boynes and Tatum with modifications. The bone graft, mean
      16 cm2 was fixed with a stud and clamp assemble or a long screw through the
      gingival crest, or with a microscrew on the lateral wall of the maxillary sinus.
      Minimal follow-up was two years. RESULTS: Mean age was 54 years (range 20-80).
      There were only two minor (hematoma) donor site problems. At the receiver site,
      there were 30 perforations of the mucosa that had no effect on the graft
      vitality. During the postoperative period, there were 2 hematomas that resolved
      spontaneously and 20 cases of dysesthesia in the V2 territory. Mid-term outcome
      (15 days to 6 months postoperatively) showed: 4 graft infections requiring
      removal in 3 cases and 6 partial resorptions requiring a new parietal bone graft
      in 3 cases. DISCUSSION: The iliac bone graft provided abundant cancellous tissue.
      The mid-term outcome was satisfactory although the postoperative problems
      resolved more slowly and were more painful than when harvesting a parietal graft.
      Mucosal perforations were frequent but reparable and did not increase
      postoperative morbidity. Infection was the most severe complication. Our
      incidence (3%) was slightly higher than reported in the literature. A possible
      explanation would be the mean height of the graft (18-20 mm) and the severity of
      the atrophies treated.

PMID- 11242771
TI  - [Prominent ears: a simple ambulatory technique under local anesthetic].
AB  - We present a simple otoplasty technique for the correction of prominent ears.
      Children can be operated starting from 8 years old, after meticulous analysis of
      the deformity which usually associates chonchal malposition and failure of scapha
      folding. Chonchal malposition can be corrected by a posterior access and chonchal
      mastoid sutures. Failure of scapha folding can be corrected by an anterior
      access, cartilage scoring and mattress sutures. Our retrospective study of 368
      patients shows 83% very good and good results. The morbidity rate is low and
      comparable to that of other studies. This technique is simple, didactic, easily
      performed under local anesthesia on an outpatient basis. Moreover, it is not
      aggressive and is easily adaptable to various deformities.

PMID- 11242770
TI  - [Mandibular fractures. Retrospective study of the experience of the Department of
      Maxillo-facial Surgery and Stomatology of the University of Poitiers Medical
      Center from 1978 to 1997].
AB  - Orthopedic or surgical repair is proposed for mandibular fractures, depending on
      schools and experience. We reviewed retrospectively 632 cases of mandibular
      fracture treated at the Poitiers University department of maxillofacial surgery
      between 1978 and 1997 to assess methods and outcome. We performed a global
      analysis and compared certain localizations with statistical tests. Different
      therapeutic protocols were used. The rate of complication was greater, for an
      equivalent initial lesion, with surgical compared with medical treatment. This
      was particularly true for fractures involving the jaw angle. There was no
      significant correlation between trauma-induced malocclusions and orthopedic or
      surgical preferences of the operators. Surgery did not lead to more sequelae than
      other techniques but did require a rigorous technique and surgical experience to
      limit complications. Joint fractures were associated with a high rate of
      complications, whatever the therapeutic method.

PMID- 11242772
TI  - [Apicoectomy: indications and surgical technique].

PMID- 11242773
TI  - [Chronic diffuse osteomyelitis of the mandible. Apropos of a case].
AB  - The incidence of osteomyelitis of the jaw has declined. Outcome is favorable with
      antibiotic therapy and surgery. We report a case in a women who experienced an
      unfavorable course with massive progressive diffusion, complicated by neoplastic
      conversion.

PMID- 11242774
TI  - [Lipoma of the infratemporal fossa. Apropos of a case].
AB  - Lipomas of the infratemporal fossa are rare. We report a case that underlines the
      importance of imaging for diagnosis and treatment. We discuss the incidence,
      pathogenesis and diagnostic problems as well as therapeutic options for lipomas
      of the infratemporal fossa.

PMID- 11242775
TI  - [Concerning "Two or three things about the DRG in stomatology and maxillofacial
      surgery" (published in the Rev Stomatol Chir Maxillofac, 1999, 100:279-87)].

PMID- 11242776
TI  - Fear of being overwhelmed and psychoanalytic theories of anxiety.

PMID- 11242777
TI  - Nietzsche's madness.

PMID- 11242778
TI  - The struggle between living and dying: the analytic treatment of a 90-year-old
      woman.

PMID- 11242779
TI  - My transforming peak experience was diagnosed as paranoid schizophrenia.
AB  - A clinical psychologist reveals how a breakthrough, transformational experience
      was perceived as a schizophrenic breakdown and led to his being placed on the
      back ward of a VA psychiatric hospital.

PMID- 11242780
TI  - Designing work experiences for persons with serious mental disorders.
AB  - Persons with serious mental disorders need to participate in productive
      activities, including mainstream, competitive employment, during the course of
      their treatment and recovery.

PMID- 11242781
TI  - On giving up on the mental health system.
AB  - This chapter describes how the author, who at the time was a practicing
      psychologist, became personally involved in advocacy for persons with mental
      illness. He also gives an overview of the activities of several organizations
      that are, or should be, advocating for this vulnerable population. He describes
      several specific programs that he sees as exemplary. Finally, the author argues
      for an approach for improving care, which he feels family and consumer advocates
      can be particularly effective in implementing.

PMID- 11242782
TI  - Psychologists, psychiatrists, and psychosis: will turf battles trump treatment?
AB  - The roles of psychology and psychiatry are rapidly changing with respect to
      people with serious mental illness. The development of these roles will seriously
      impact the quality of care available for this vulnerable population.

PMID- 11242783
TI  - Relapse prevention in serious mental illness.
AB  - The current emphasis on relapse prevention in serious mental illness offers
      psychologists new opportunities and roles for which they are uniquely suited.

PMID- 11242784
TI  - Treatment, management, and control: improving outcomes through more treatment and
      less control.
AB  - Outcomes in psychiatric care are improved by expanding treatment options and
      reducing dependence on management and control interventions.

PMID- 11242785
TI  - A psychological view of people with serious mental illness.
AB  - Focusing on a variety of relevant psychological theories, this chapter addresses
      important elements in the recovery process for people with serious mental
      disabilities.

PMID- 11242786
TI  - Mothers with serious mental illness.
AB  - Mental health services have generally ignored the parenting needs of women with
      serious mental illness. This chapter identifies the parenting risks and strengths
      that these women display, as well as the opportunities available to psychologists
      to play a key role in improving mother and child outcomes.

PMID- 11242787
TI  - Consumers/survivors/ex-patients as change facilitators.
AB  - The expertise gleaned from being a patient in a psychiatric hospital is used to
      train hospital staff in what is helpful to patients and what hurts. The trainers
      are consumers/survivors/ex-patients in different stages of recovery.

PMID- 11242788
TI  - Measuring and reporting errors in surgical pathology. Lessons from gynecologic
      cytology.
AB  - Substantial improvements in measuring and reporting errors in gynecologic
      cytology have been made during the last decade. Measuring and reporting errors in
      surgical pathology recently has gained renewed interest. However, review of
      current literature demonstrates mistakes in how these data are measured and
      reported. Error rates have been reported from review of consecutive material,
      biopsy material, and consultation material and range from 0.25% to 43%. Errors
      have been divided into anatomic regions and specimen types and separated
      according to their clinical significance. However, to be comparable, errors must
      be reported in reference to the incidence of disease and not to overall caseload.
      Blinding and reviewer error have been addressed only rarely, and the true
      incidence of errors is almost certainly higher than reported. "Gold standards"
      are not well defined. In addition, available data strongly suggest that the
      greatest source of error is with false-negative diagnoses, which are detected
      only rarely by review of consultation material. Most of these issues have been
      addressed in the gynecologic cytology literature. Errors in surgical pathology
      are more common than generally believed, and efforts should be made to define
      methods that allow appropriate interlaboratory comparisons.

PMID- 11242790
TI  - Congenital-infantile fibrosarcoma. A clinicopathologic study of 10 cases and
      molecular detection of the ETV6-NTRK3 fusion transcripts using paraffin-embedded
      tissues.
AB  - Congenital-infantile fibrosarcoma (CIFS) is a relatively indolent sarcoma that
      should be distinguished from more aggressive spindle cell sarcomas of childhood.
      CIFSs have been found to have a novel recurrent reciprocal translocation
      t(12;15)(p13;q25) resulting in the gene fusion ETV6-NTRK3 (ETS variant gene 6;
      neurotrophic tyrosine kinase receptor type 3). We studied immunohistochemical
      expression of NTRK3, and conducted a reverse transcription-polymerase chain
      reaction (RT-PCR) assay to detect the ETV6-NTRK3 fusion transcripts using
      archival formalin-fixed paraffin-embedded tissues from 10 CIFSs. Thirty-eight
      other spindle cell tumors were included as controls. The ETV6-NTRK3 fusion
      transcripts were identified in 7 (70%) of 10 CIFSs. Nucleotide sequence analysis
      showed that the fusion occurred between ETV6 exon 5 and NTRK3 exon 13. The 38
      control tumors were negative for the fusion transcript. Immunohistochemically,
      CIFSs consistently expressed NTRK3. But the expression of NTRK3 also was observed
      in 22 of 38 control tumors. These results show the diagnostic usefulness of RT
      PCR methods to detect ETV6-NTRK3 fusion transcripts in archival formalin-fixed
      paraffin-embedded tissue and the important role of NTRK3 in the development of
      CIFS, despite its being a protein of little importance in differential diagnosis.

PMID- 11242789
TI  - The significance of perivascular inflammation in the absence of arteritis in
      temporal artery biopsy specimens.
AB  - We retrospectively compared 81 temporal artery biopsy specimens demonstrating
      perivascular inflammation without evidence of temporal arteritis and 76 specimens
      demonstrating no inflammation. Patients with perivascular inflammation included
      43 women (mean age, 71.2 years). Nineteen patients met the 1990 American College
      of Rheumatology (ACR) criteria for the diagnosis of temporal arteritis. All
      patients demonstrated chronic perivascular inflammation consisting primarily of
      lymphocytes. Granulomas were noted in 4 specimens. Internal elastic lamina
      disruption, intimal fibroplasia, and dystrophic calcification were noted in 86
      arteries examined. Fibrosis or scarring of the vessel walls was observed in 10
      specimens. Corticosteroid therapy was beneficial to 33 of 56 patients. In
      patients with no evidence of inflammation (50 women; mean age, 66.6 years), 21
      met ACR criteria for temporal arteritis. Histologically, disruption of the
      elastic lamina was noted in 75 of 81 arteries biopsied, intimal fibroplasia in
      66, microcalcifications in 5, and fibrosis or scarring in 5. In this group, 47
      patients received corticosteroid therapy; clinical improvement was noted in 28.
      Patients with chronic perivascular inflammation but no arteritis seem no more
      likely to have temporal arteritis on clinical grounds than similar patients
      without inflammation on biopsy.

PMID- 11242791
TI  - The effect of electrothermal cautery-assisted resection of diminutive colonic
      polyps on histopathologic diagnosis.
AB  - We examined diminutive colonic polyps to identify relationships between thermal
      electrocoagulation or resection trauma cytologic artifacts, type of thermal
      electrocoagulation, polyp size, and the interobserver variation among 3
      pathologists. The 3 pathologists independently evaluated 119 colonic polyps 5 mm
      or less in maximum dimension for diagnosis and degree of thermal
      electrocoagulation or resection trauma cytologic artifacts. The maximum dimension
      of the polyps and type of thermal electrocoagulation were recorded. The average
      percentage of polyps in which a definitive diagnosis could not be made because of
      cytologic artifacts was 16.5% (range, 11.8%-19.3%). Decreasing polyp size was
      associated linearly with the inability to make a definitive diagnosis owing to
      cytologic artifacts. Polyps smaller than 2 mm significantly more often could not
      be definitively diagnosed by at least 1 pathologist owing to cytologic artifacts,
      including some polyps that were excised without thermal electrocautery.
      Interobserver variation increased with decreasing polyp dimension. Two
      millimeters seems to represent a cut point, below which the likelihood that a
      definitive diagnosis can be made can be increased if thermal electrocoagulation
      is used. This small size seems to make them especially susceptible to
      cytologically injurious forces.

PMID- 11242792
TI  - Pathologic features of breast cancers in women with previous benign breast
      disease.
AB  - To compare pathologic features of the cancers arising after different types of
      benign breast disease (BBD), we reviewed the invasive breast cancer slides of 169
      women with a previous benign biopsy result. Lesions were categorized previously
      as nonproliferative, proliferative without atypia, or atypical hyperplasia.
      Pathologic features of the cancers were evaluated without knowledge of the
      previous BBD category. Estrogen and progesterone receptor immunohistochemistry
      was performed on available tissue blocks. The median times between a benign
      result and cancer were 100, 124, and 92 months for women with nonproliferative
      lesions, proliferative lesions without atypia, and atypical hyperplasia,
      respectively. Cancers in the 3 groups did not differ significantly in tumor size,
      axillary lymph node status, or histologic grade, and there was no significant
      difference in the distribution of histologic types of breast cancer. Lymphatic
      vessel invasion, extensive intraductal component, and hormone receptor status did
      not differ among BBD categories. The pathologic features of breast cancers that
      develop in women with a previous benign biopsy result do not vary according to
      the histologic category of the previous BBD.

PMID- 11242793
TI  - Why do frozen sections have limited value in encapsulated or minimally invasive
      follicular carcinoma of the thyroid?
AB  - The diagnosis of encapsulated or minimally invasive follicular carcinoma of the
      thyroid requires the proof of vascular or capsular invasion. The aim of the
      present study was to evaluate the relationship between intraoperative diagnosis
      (benign, suggestive of carcinoma, or malignant) and the final histopathologic
      criteria for encapsulated or minimally invasive follicular carcinoma (tumor size,
      capsular invasion, vascular invasion, and differentiation). This was a
      retrospective study of 63 cases of encapsulated or minimally invasive carcinomas,
      with the final histopathologic diagnosis taken as the "gold standard." The
      sensitivity of frozen sections for the diagnosis of malignant neoplasm was 17%.
      The median number of vascular invasions was 1, identified with a mean number of 9
      paraffin-blocks of the tumor. In most cases, intraoperative frozen sections are
      unable to establish the proof of malignant neoplasm. Intraoperative study of
      tumor differentiation is useful to select follicular tumors that require a rapid
      definitive diagnosis and a completion thyroidectomy within 48 to 72 hours (73% of
      the cases in our study).

PMID- 11242794
TI  - EDTA-dependent platelet phagocytosis. A cytochemical, ultrastructural, and
      functional characterization.
AB  - Platelet satellitosis of polymorphonuclear cells is a phenomenon induced or
      enhanced by the anticoagulant EDTA. In contrast with previously reported studies,
      the subject in the present case did not demonstrate platelet satellitism but was
      profoundly pseudothrombocytopenic owing to platelet phagocytosis. Virtually all
      polymorphonuclear leukocytes and monocytes contained numerous ingested platelets
      in contrast with previous cases in which phagocytosis was observed only rarely
      and involved ingestion of single cells. The phenomenon was documented by
      immunocytochemical staining and transmission electron microscopy. Autoantibodies
      were detected in EDTA-anticoagulated blood. However, neither platelet antibody
      nor phagocytosis was present when heparin, acid-citrate dextrose, or citrate was
      used as an alternative anticoagulant. The antibody was not temperature dependent.
      Mixing studies showed the transfer of the phagocytosis phenomenon to healthy
      donors. Although platelet function assays are typically normal in EDTA-dependent
      platelet satellitism, this subject showed no secondary aggregation wave in
      response to adenosine diphosphate and depressed adenosine triphosphate release
      with collagen, adenosine diphosphate, and arachidonic acid.

PMID- 11242795
TI  - Large cell lymphoma transformation of chronic lymphocytic leukemia/small
      lymphocytic lymphoma. A flow cytometric analysis of seven cases.
AB  - We studied 7 cases of large cell transformation of chronic lymphocytic
      leukemia/small lymphocytic lymphoma (CLL/SLL) immunophenotyped by multiparameter
      flow cytometry. The 6 women and 1 man ranged in age from 45 to 91 years. All had
      previous or concurrent evidence of CLL/SLL. Morphologic features and sites of
      involvement of the diffuse large B-cell lymphoma (DLBCL) were heterogeneous; 2
      cases had paraimmunoblastic morphologic features. Six DLBCLs had an
      immunophenotype consistent with CLL: CD19+, CD5+, CD23+, and FMC7 negative (3
      cases) or very dim (2 cases); 1 case was not studied for FMC7. CD20 was dim in 3
      of these, moderate to bright in 2, and variable in 1. Surface immunoglobulin was
      dim in 2 cases and moderate or bright in 4. Five of 6 expressed CD38. Comparison
      with the immunophenotypes of the previous or coexistent CLL/SLL (4 of 6 cases)
      revealed minor modulations in antigen expression but no major alterations. The
      seventh DLBCL lacked CD5 expression, but otherwise had immunophenotypic features
      similar to CLL. These findings indicate that DLBCL arising in CLL/SLL tends to
      retain a CLL immunophenotype, in contrast with de novo CD5+ large cell lymphomas
      that uncommonly express such a phenotype.

PMID- 11242796
TI  - Aberrant expression of T-cell-associated antigens on B-cell non-Hodgkin
      lymphomas.
AB  - We describe 9 well-characterized cases of B-cell non-Hodgkin lymphoma (NHL) that
      showed aberrant expression of T-cell-associated antigens by 2-color flow
      cytometry. Cases were as follows: chronic lymphocytic leukemia/small lymphocytic
      lymphoma, 4; follicle center cell lymphoma, 2; mantle cell lymphoma, 1; and
      diffuse large B-cell lymphoma, 2. CD2 was the most commonly expressed antigen (5
      cases). CD8 and CD7 were identified in 2 cases each, including 1 case that
      expressed both CD7 and CD4. The disease course and response to treatment were
      compatible with the type and stage of lymphoma. No unusually aggressive behavior
      was noted in any case. A control group of 59 cases of benign lymph nodes analyzed
      during the same period showed no aberrant expression of T-cell-associated
      antigens; thus, such expression is not a feature of benign lymphoid
      proliferations. Study of these B-cell lymphomas may prove invaluable to study
      aberrant activation of silent or repressed T-cell differentiation genes. CD2
      expressing B-cell NHLs may represent clonal expansion of CD2+ B lymphocytes that
      normally constitute a small fraction of peripheral B lymphocytes and should not
      be confused with composite B- and T-cell lymphomas. Unless aggressive behavior is
      noted consistently, no aggressive treatment is justified.

PMID- 11242797
TI  - Cyclin D3 expression in non-Hodgkin lymphoma. Correlation with other cell cycle
      regulators and clinical features.
AB  - Cyclin D3 is the most widely expressed D-type cyclin and can be rate limiting for
      G1/S transition. To study the expression of cyclin D3 in non-Hodgkin lymphoma,
      samples from 198 previously untreated patients with lymphoma from a prospectively
      collected, population-based lymphoma registry were analyzed immunohistochemically
      for cyclin D3 expression. In 43 lymphomas (21.7%), cyclin D3 was overexpressed. T
      cell lymphomas more frequently overexpressed cyclin D3 than B-cell lymphomas.
      Furthermore, cyclin D3-overexpressing indolent lymphomas were associated with
      higher proliferation rate, higher p21Waf1 expression, lower p27Kip1 expression,
      and altered p53. Cyclin D3 overexpression identified a subgroup of patients with
      indolent B-cell lymphoma with adverse clinical features: patients were older,
      more frequently had "B" symptoms and extranodal involvement, and were more
      frequently in the high-intermediate or high-risk International Prognostic Index
      groups. At univariate analysis of indolent lymphomas, cyclin D3 overexpression
      was associated significantly with poor overall survival and poor relapse-free
      survival. The statistical significance was retained on multivariate analysis of
      overall survival and relapse-free survival. Our results suggest that cyclin D3 is
      expressed differentially among lymphoma subtypes and that overexpression might
      identify a subpopulation of patients with indolent lymphoma with adverse clinical
      features and poor outcome.

PMID- 11242798
TI  - The T-cell chemokine receptor CXCR3 is expressed highly in low-grade mycosis
      fungoides.
AB  - Three chemokines, Mig, IP-10, and I-TAC, are expressed highly in the epidermis.
      We examined the expression of the receptor for these chemokines, CXCR3, in
      cutaneous T-cell lymphoma. We compared CXCR3 expression with that of cutaneous
      lymphocyte antigen (CLA) and the activation marker CD30. CXCR3 was expressed by
      at least a subset of tumor lymphocytes in all 25 cases of low-grade mycosis
      fungoides (MF), with most cells positive in 20 cases. In progressed or
      transformed MF, CXCR3 expression was noted in 5 of 22 cases. In 4 of 5 MF cases
      with sequential biopsy specimens, large cell transformation was accompanied by
      loss of CXCR3 expression. In contrast, CLA was expressed in 35 of 42 MF cases
      with no significant differences in expression level between low-grade and
      transformed cases. In other lymphomas, CXCR3 was expressed in 4 of 4 cases of
      lymphomatoid papulosis, 3 of 4 cases of CD8+ cutaneous T-cell lymphoma, and 3 of
      6 cases of systemic T-cell lymphoma in skin, but not in 10 cases of cutaneous
      anaplastic large cell lymphoma. CXCR3 expression was associated with
      epidermotropic T-cell tumors but was largely absent in dermal-based tumors. This
      phenotypic change likely influences the loss of epidermal localization.

PMID- 11242799
TI  - Evaluation of the automatic fluorescent image analyzer, Image Titer, for
      quantitative analysis of antinuclear antibodies.
AB  - By making comparisons with the usual manual method, we evaluated an automatic
      fluorescent image analyzer (Image Titer, Tripath Imaging, Burlington NC), the
      software for which was developed to simplify measuring indirect immunofluorescent
      antinuclear antibodies (FANAs). In this new system, images of the stained sample
      are displayed, and it measures the FANA titer and staining pattern using only 1
      slide per subject and does not required the staining of a series of diluted
      samples as does the manual method. This system showed good reproducibility and
      linearity for 4 types of control serum samples (with homogeneous, speckled,
      discrete speckled, and nucleolar staining patterns). In 132 serum samples,
      consistency between the methods was 100% for the FANA staining pattern and 93.9%
      for the FANA titer. The Image Titer system detected each pattern in samples with
      2 mixed patterns. This system should partly reduce labor and lead to results with
      minimum differences among individuals, including newly trained persons.

PMID- 11242800
TI  - Improved laboratory confirmation of heparin-induced thrombocytopenia type II.
      Time course of antibodies and combination of antigen and biologic assays.
AB  - We studied whether laboratory confirmation of heparin-induced thrombocytopenia
      (HIT) can be improved after antigen clearance by determining free antibody and
      combining the results of an antigenic and a biologic assay. Blood samples taken
      over 40 days in 14 patients with HIT with thromboembolism underwent fluorescence
      linked immunofiltration and the carbon 14-serotonin release assays. Of the 14
      patients, 11 showed positive results in both assays at day 1 after stopping
      heparin. The 3 patients with negative results seroconverted in one or both assays
      during the subsequent 7 days. Combining the positive results of the assays
      increased the sensitivity from 85% at day 1 to 100% at day 7. Assay results
      became negative in all patients within 40 days. The platelet count normalized
      between days 2 and 9 after withdrawal of heparin. It is assumed that the free
      antibody can be detected after withdrawal of heparin and after clearance of the
      platelet factor 4-heparin complex in patients with HIT.

PMID- 11242801
TI  - Real-time polymerase chain reaction with fluorescent hybridization probes for the
      detection of prevalent mutations causing common thrombophilic and iron overload
      phenotypes.
AB  - We evaluated more than 450 patients with thrombophilia or iron overload for the
      presence of a factor V Leiden (R506Q), prothrombin G20210A, or HFE C282Y mutation
      using a standard method (polymerase chain reaction [PCR]-restriction fragment
      length polymorphism) and a comparative real-time PCR fluorescent resonance energy
      transfer (FRET) hybridization probe melting curve method. There was 100%
      concordance between the genotypes ascertained by the 2 methods (at each loci). In
      addition, phenotypic biochemical laboratory parameters measured on a subset of
      referred patients correlated with their respective genotypes. In the iron
      overload cohort, HFE C282Y homozygotes (n = 74) had significantly higher (P <
      .0001) transferrin saturation levels (74% +/- 25%) than did nonhomozygotes (n =
      340; 51.4% +/- 28%), suggesting a genotype-dependent increase in body iron loads.
      In the thrombophilic cohort, the degree of activated protein C resistance (APCR),
      measured by a clotting time-based test, was associated significantly with the
      presence of 0 (n = 255; APCR = 2.59 +/- 0.26), 1 (n = 84; APCR = 1.61 +/- 0.13),
      or 2 (n = 5; APCR = 1.16 +/- 0.04) copies of the mutant factor V Leiden allele.
      As the fluorescent genotyping method required no postamplification manipulation,
      genotypes could be determined more quickly and with minimized risk of handling
      errors or amplicon contamination. In addition to these practical advantages, the
      FRET method is diagnostically accurate and clinically predictive of phenotypic,
      disease-associated manifestations.

PMID- 11242802
TI  - An interlaboratory study of a candidate reference method for platelet counting.
AB  - A multinational interlaboratory task force explored the important variables of
      platelet reference counting and developed a candidate flow cytometric reference
      method based on the RBC/platelet ratio. A multicenter comparison was performed to
      determine whether the method met the necessary criteria and was precise enough to
      be recommended as a new reference method. Each laboratory analyzed serial
      dilutions of normal specimens, stabilized material, and at least 60 patient
      specimens with a range of platelet counts from 1 to 400 x 10(3)/microL (1-400 x
      10(9)/L). Pooled analysis of the serial dilutions showed that RBC-platelet and
      RBC-RBC coincidence events became negligible at sufficiently high dilutions
      (i.e., > 1:1,000). All laboratories demonstrated excellent intra-assay and
      acceptable interlaboratory precision. Two antibodies (CD61 and CD41) were used
      for identifying platelets and individually gave acceptable results, but in a
      minority of samples, staining differences were observed. The optimum method thus
      uses a double-labeling procedure with a final dilution factor of 1:1,000. The
      study demonstrated that this method meets the criteria for a reference platelet
      count.

PMID- 11242803
TI  - Expression of transforming growth factor beta-1 in chronic hepatitis and
      hepatocellular carcinoma associated with hepatitis C virus infection.
AB  - BACKGROUND: Transforming growth factor beta-1 (TGF beta 1) has been suggested to
      play a role in the development, growth or progression of hepatocellular carcinoma
      (HCC). Genotype and serum titer of HCV also affect the occurrence of HCC in
      chronic hepatitis C. In this study, we were to evaluate the effects of genotype
      or serum titer of HCV on the expression of TGF beta 1. We also intended to
      examine the correlation between the up-regulation of TGF beta 1 and the
      association with HCC in patients with chronic hepatitis C. METHODS: We studied 19
      patients with chronic hepatitis C and 18 with HCC associated with HCV infection.
      HCV genotype was determined by line probe reverse hybridization assay and the
      amount of HCV-RNA was quantitated by branched DNA signal amplification assay.
      Serum TGF beta 1 level was measured by enzyme linked immunosorbent assay.
      RESULTS: HCV genotypes of patients with HCC were similar to those without it.
      Serum HCV-RNA titer was higher in genotype 1b than in non-1b (p < 0.05). Serum
      TGF beta 1 levels were higher in HCC than in chronic hepatitis (p < 0.05).
      However, there was no significant difference in the serum TGF beta 1 level
      between genotype 1b and non-1b. Also, it was not correlated with the serum HCV
      RNA titer or alanine aminotransferase levels. CONCLUSION: TGF beta 1 seems to be
      overexpressed in HCC compared to that of chronic hepatitis C: it was not affected
      by serum ALT levels, genotype or serum HCV titer. It is suggested that TGF beta 1
      may be associated with the malignant transformation of hepatocyte or the
      progression of HCV-associated HCC.

PMID- 11242804
TI  - Expression of tissue inhibitors of metalloproteinases (TIMPs) in hepatocellular
      carcinoma.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) have been implicated in the
      remodelling of extracellular matrix (ECM), including basement membrane. ECM
      remodelling is associated with pathological processes, including hepatic
      fibrosis, tumor invasion and metastasis. Tissue inhibitors of metalloproteinase
      (TIMP)-1 and TIMP-2 were known to inhibit MMP-9 and MMP-2, respectively. In the
      present study, we examined the expression of TIMP-1 and TIMP-2 in surgical
      specimen pairs of hepatocellular carcinoma and nontumoral liver and the
      correlation between their expression and clinicopathological characteristics.
      METHODS: The localization of both transcripts and protein of TIMP-1 and TIMP-2
      was studied by using in situ hybridization and immunohistochemistry. RESULTS:
      TIMP-1 and TIMP-2 mRNA transcripts were found in tumor cells, hepatocyte,
      sinusoidal cells, endothelial cells and stromal cells. Signal intensity of TIMP-1
      was stronger than that of TIMP-2. The results of immunohistochemical stainings
      were concordant with those obtained by in situ hybridization. Expression of TIMP
      1 and TIMP-2 was observed in tumorous tissue, in nontumorous tissue and in the
      portions of the tumors adjacent to the capsules. However, a clear difference in
      TIMP-1 and TIMP-2 mRNA expression was not observed among the three tissue types.
      The intensity of TIMP-2 expression was generally weaker than that of TIMP-1, and
      the intensity of TIMP-1 and TIMP-2 mRNA expression did not correlate with
      variable clinicopathological characteristics. CONCLUSION: TIMPs was expressed in
      tumor cells and many cell types of the nontumoral liver. Further investigations
      for TIMPs' unknown functional role are needed.

PMID- 11242805
TI  - Clinical results of the transjugular intrahepatic portosystemic shunt (TIPS) for
      the treatment of variceal bleeding.
AB  - BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) has been
      popularized for the treatment of refractory variceal bleeding. The aim of this
      study was to assess the safety and long-term effect of TIPS in the treatment of
      variceal bleeding that is not controlled with pharmacological and endoscopic
      treatment. METHODS: Thirty-six patients who underwent transjugular intrahepatic
      portosystemic shunt (TIPS) due to refractory variceal bleeding were included in
      the study. The effectiveness of portal decompression and bleeding control was
      evaluated. Upper gastrointestinal endoscopy was performed to analyse the degree
      of varices and portal hypertensive gastropathy (PHG) before TIPS procedure and
      one to three weeks after TIPS. Angiography was performed in surviving patients,
      if bleeding recurred, or if ultrasonography or endoscopy suggested stent
      dysfunction. RESULTS: TIPS were successfully placed in 36 of 38 patients (94.6%).
      TIPS achieved hemostasis of variceal bleeding in 34 patients (94.4%). Portal
      venous pressure decreased from an initial average of 28.7 +/- 7.9 to 23.2 +/- 9.4
      mmHg after TIPS (p < 0.05). The portosystemic pressure gradient was significantly
      decreased from 15.5 +/- 6.3 to 7.8 +/- 4.1 mmHg (p < 0.01). The degree of
      esophagogastric varices and PHG was significantly improved after TIPS. The total
      length of follow-up was from one day to 54 months (mean: 355 days). The actuarial
      probability of survival was 83% at one year and 74% at two years. Overall, 16
      episodes of stent dysfunction were diagnosed during follow-up. Stent revision by
      means of angioplasty was successfully performed in 14 of these episodes.
      CONCLUSION: TIPS is an effective and reliable nonoperative means of lowering
      portal pressure. This procedure has proved useful in the management of acute
      variceal bleeding refractory to endoscopic treatment. Surveillance by
      ultrasonography, endoscopy, and angiographic intervention is useful for the
      maintenance of shunt patency.

PMID- 11242806
TI  - Helicobacter pylori in dental plaque and saliva.
AB  - BACKGROUND: About half of the world population is infected with H. pylori, but
      the transmission and the source of this infection are still unclear. Recently,
      dental plaque (DP) and saliva have been implicated as possible sources of H.
      pylori infection. This study was done to investigate the detection rates of H.
      pylori in the DP and saliva by use of PCR depending on H. pylori infection state
      of gastric mucosa. METHODS: In 46 subjects, gastric H. pylori colonization was
      evaluated with CLO test, microscopy of Gram stained mucosal smear, culture and
      histology after modified Giemsa staining in the antrum and body, respectively. A
      patient was regarded as H. pylori positive if one or more of the four
      aforementioned test methods demonstrated H. pylori colonization of the gastric
      mucosa. For detection of H. pylori in the DP and saliva, PCR assay was done with
      ET4-U and ET4-L primers. To estimate the sensitivity and specificity of this PCR,
      H. pylori positivity was evaluated in the antrum and body, separately. RESULTS:
      The sensitivity of mucosal PCR was 50.0% (27/54) and the specificity 86.8%
      (33/38). When a subject was regarded as H. pyloi positive, if either antrum or
      body mucosal H. pylori was is positive, the positive rate of mucosal PCR was
      62.1% (18 subjects) in the 29 H. pylori-positive and 17.6% (3 subjects) in the 17
      H. pylori-negative subjects. DP PCR was positive in 2 of 29 H. pylori-positive
      subjects (6.9%) and none in the 17 H. pylori-negative (0%). Saliva PCR was
      positive in 4 of 14 H. pylori-positive subjects (28.6%) and none of 6 H. pylori
      negative (0%). CONCLUSION: The detection rates of H. pylori in DP and saliva by
      PCR were rather low, 6.9% and 28.6%, respectively, and these rates might have
      been underestimated by low sensitivity of the PCR method used in this study.
      However, the results that H. pylori was found in the DP and saliva suggest that
      the oral cavity can perform a role as a reservoir of H. pylori in Korea.

PMID- 11242807
TI  - Serum insulin, proinsulin and proinsulin/insulin ratio in type 2 diabetic
      patients: as an index of beta-cell function or insulin resistance.
AB  - BACKGROUND: Although insulin resistance and decreased insulin secretion are
      characteristics of established type 2 DM, which of these metabolic abnormalities
      is the primary determinant of type 2 DM is controversial. It is also not well
      known how insulin resistance and beta cell dysfunction influence serum insulin,
      proinsulin, proinsulin/insulin ratio in type 2 DM. METHODS: We compared serum
      insulin, proinsulin and proinsulin/insulin ratio in type 2 diabetic patients and
      control subjects. We also investigated the relationship between serum insulin,
      proinsulin and proinsulin/insulin ratio and several biochemical markers which
      represent insulin resistance or beta cell function. RESULTS: Insulin, proinsulin
      and proinsulin/insulin ratio were significantly higher in type 2 DM than
      control(p < 0.001). In diabetic patients, total insulin level was correlated with
      urinary albumin excretion rates(r = 0.224, p = 0.025) and body mass index(r =
      0.269, p = 0.014). Proinsulin level was correlated with fasting C-peptide(r =
      0.43, p = 0.002), postprandial 2 hour blood glucose(r = 0.213, p = 0.05) and
      triglyceride(r = 0.28, p = 0.022). Proinsulin/insulin ratio was positively
      correlated with fasting C-peptide(r = 0.236, p = 0.031), fasting blood glucose (r
      = 0.264, p = 0.015), postprandial 2 hour blood glucose(r = 0.277, p = 0.001) and
      triglyceride(r = 0.428, p < 0.001). In control subjects, insulin level was
      correlated with triglyceride(r = 0.366, p = 0.002). Proinsulin/insulin ratio was
      correlated with age(r = 0.241, p = 0.044). CONCLUSION: The serum levels of
      insulin and proinsulin seem to be associated with several markers of insulin
      resistance. Whereas proinsulin/insulin ratio might represent beta cell function
      rather than insulin resistance. But more studies are needed to clarify the
      mechanisms of elevated proinsulin/insulin ratio in type 2 DM.

PMID- 11242808
TI  - Increased prevalence of autoimmune thyroid disease in patients with type 1
      diabetes.
AB  - BACKGROUND: Type 1 diabetes mellitus is frequently associated with other
      autoimmune diseases. The occurrence of common features of autoimmune diseases and
      the coassociation of multiple autoimmune diseases in the same individual or
      family supports the notion that there may be common genetic factors. METHODS: To
      investigate potential clustering of autoimmune thyroid disease (ATD) among type 1
      diabetes patients and the contribution of common susceptibility genes to this,
      HLA DR/DQ alleles as well as antithyroid autoantibodies were measured in 115
      Korean patients with type 1 diabetes and their 96 first-degree family members.
      RESULTS: Twenty-five percent of the patients had ATD, whereas 3 of 36 (8%) age
      matched normal controls had ATD (RR = 3.7, p < 0.05). Twenty-six of ninty-six
      (27%) type 1 diabetes family members had ATD. No differences in the distribution
      of HLA alleles/haplotypes and genotypes between the patients with and without ATD
      were found. CONCLUSION: From this finding, we could assess that individuals with
      type 1 diabetes and their relatives frequently develop ATD, perhaps due to common
      susceptibility genes that are shared among first degree relatives.

PMID- 11242809
TI  - New ADA criteria in the Korean population: fasting blood glucose is not enough
      for diagnosis of mild diabetes especially in the elderly.
AB  - BACKGROUND: To compare the 1997 American Diabetes Association (ADA) criteria with
      the 1985 World Health Organization (WHO) criteria in categorization of the
      diabetes diagnostic status of Koreans and to define clinical characteristics of
      subjects diagnosed differently by the two criteria. METHODS: In 810 Korean
      subjects, we analyzed blood glucose and insulin response during 75 g oral glucose
      tolerance test (OGTT). According to current WHO criteria, the cutoff values of
      FPG which distinguish normal and IGT from diabetes were determined. Then the
      subjects were categorized according to both WHO and ADA criteria. The clinical
      characteristics of the subjects with different diagnostic categories by the two
      criteria were defined. RESULTS: The FPG cut point distinguishing diabetes from
      IGT was 117 mg/dl, and from normal was 110 mg/dl. The overall agreement between
      the ADA criteria and the WHO criteria was moderate, as reflected in the kappa of
      0.45. 141 of subjects categorized diabetes by WHO criteria were not diagnosed
      with ADA criteria. These discordant subjects were older in age and showed blunted
      early insulin response than concordant normal subjects. CONCLUSION: These results
      suggest that mild diabetes by the WHO criteria, especially in the elderly, would
      not be diagnosed as diabetes by the ADA FPG criteria only. Thus, in a group at
      high risk for developing diabetes or in a relatively older age group, we should
      continue using the OGTT.

PMID- 11242810
TI  - Gentamicin induced apoptosis of renal tubular epithelial (LLC-PK1) cells.
AB  - Nephrotoxicity is a major limiting factor in the use of aminoglycoside
      antibiotics, the mechanisms for which are still speculative. To clarify the
      mechanisms of renal tubular cell death induced by aminoglycosides, we examined
      the renal proximal tubule-like cell line, LLC-PK1, after inducing apoptosis
      through a chronic treatment with gentamicin (GM). Changes in the expression of
      the Fas were also investigated. On flow cytometric analysis, 5.7 +/- 3.3% of the
      control cells appeared in a region of decreased forward light scatter and
      increased side light scatter, where both indices represent the characteristics of
      apoptotic cell death. Compared to the control, treatment with 10 mM of GM for 15
      days significantly increased the proportion of cells in the apoptotic region to
      23.9 +/- 8.5%. This finding was supported by electrophoretic analysis of the DNA
      extracted from the GM-treated cells, where a series of bands corresponding to
      integer multiples of 180 to 200 base pairs was visualized. However, the 15-day GM
      treatment did not cause a significant elevation in the expression of the 45 kD
      Fas protein, the cell surface molecule that stimulates apoptosis, by Western blot
      analysis. In conclusion, long-term exposure to GM induces apoptosis of the renal
      tubular epithelial cells, and this process may contribute to some of the
      aminoglycoside nephrotoxicities. Further studies are needed on the mechanism(s)
      of apoptosis induced by GM.

PMID- 11242811
TI  - Effects of mixed chimerism and immune modulation on GVHD, disease recurrence and
      survival after HLA-identical marrow transplantation for hematologic malignancies.
AB  - BACKGROUND: The success of allogeneic bone marrow transplantation(allo-BMT) is
      affected by underlying disease relapse. Although mixed chimerism(MC) is not
      necessarily a poor prognostic factor, several groups have suggested that MC is
      associated with an increased risk of disease relapse. There is evidence that
      patients with MC benefit from additional immunotherapy if the treatment is
      started in minimal residual disease status(mixed chimerism status), not in frank
      hematological relapse. The purposes of this study are to evaluate 1) the risk for
      relapse or graft rejection in correlation to persistent MC status after allo-BMT,
      and 2) the possibility of preventing relapse by immune modulation treatments
      (withdrawal or rapid taper-off of post-transplant immuno-suppression, additional
      interferon treatment, or the administration of donor lymphocytes) in hematologic
      malignancies. PATIENTS AND METHODS: Of 337 allogeneic donor-recipient pairs
      between March 1996 and August 1998, 12 patients who showed persistent or
      progressive MC and who received immune modulation treatments were evaluated.
      Twelve patients, median age 31 years(range 9 to 39 years), received an allo-BMT
      for: acute myelogenous leukemia(AML, n = 5), chronic myelogenous leukemia(CML, n
      = 4), acute lymphocytic leukemia(ALL, n = 3). Serial polymerase chain
      reaction(PCR) analysis of YNZ 22-, 33.6-minisatellites or Y chromosome-specific
      PCR analysis at short term intervals(pre- and post-transplant 1, 3, 6, 9, ...
      months) was performed. Once MC was detected, immune modulation treatments on the
      basis of increasing MC in an early phase of recurrence of underlying disease were
      started. RESULTS: Nine of 12 patients converted to complete chimerism(CC) (AML
      5/5, CML 3/4, ALL 1/3). Four of 9 CC patients developed graft-versus-host
      disease(GVHD) grade < or = 2 during immune modulation. All were treated
      successfully with steroids. Three patients who were not converted to CC showed
      relapse of underlying diseases or graft failure. CONCLUSION: The results
      demonstrate that, in patients with hematologic malignancies after allo-BMT,
      persistent MC is associated with relapse of underlying diseases or graft failure.
      Furthermore, when patients receive early immune modulation treatment, MC can be
      changed to complete donor pattern chimerism and ultimately prevent relapse.

PMID- 11242812
TI  - Recurrent asystoles associated with vasovagal reaction during venipuncture.
AB  - A 17-year-old high school student presented with a history of habitual faintings.
      On 24-hour Holter monitoring, cardiac asystoles were recorded, the longest
      lasting approximately 7 or 8 seconds during venipuncture procedures. The asystole
      associated with venipuncture demonstrated the cardioinhibitory effects of
      vasovagal reaction with blood-injury phobia. He also had a positive response
      during head-up tilt test showing hypotension and relative bradycardia after
      intravenous isoproterenol injection. After administration of oral beta blocker,
      he did not show further or recurrent cardiac asystole during blood injury
      procedure on electrocardiographic examination. Venipuncture is the most common
      invasive medical procedure performed in hospital settings. While venipuncture is
      considered to be reasonably safe, serious complication may occur even when only a
      small volume of blood is withdrawn. Therefore, medical personnel should be
      prepared to provide appropriate care.

PMID- 11242813
TI  - Multicentric biatrial myxoma in a young female patient: case report.
AB  - We report a case of multicentric, biatrial cardiac myxoma in a 29-year-old female
      who complained of exertional dyspnea, abdominal distension and peripheral edema.
      Any other associated skin lesions, breast mass or endocrine disorder presenting
      complex form were' not seen on her. Also, there was no contributory medical
      history, hypertension and diabetes mellitus. By using transthoracic
      echocardiography, we identified a biatrial myxoma attached to the interatrial
      septum. During surgical excision, we found a large right atrial myxoma with
      extension through the fossa ovalis into the left atrium and small myxoma attached
      to the right atrial free wall. After successful resection of interatrial septum
      and free wall, atrial septal defect was created during the resection and safely
      repaired by bovine pericardial patch.

PMID- 11242814
TI  - A case of endobronchial actinomycosis.
AB  - Actinomycosis is an infectious disease caused by certain Actinomyces species.
      Actinomyces are Gram-positive, non-spore forming organisms characterized by
      obligate or facultative anaerobic rods that normally inhabit anaerobic niches of
      the human oral cavity. Cervicofacial, abdominal, pelvic and thoracic infections
      of Actinomyces are not uncommon, but endobronchial actinomycosis is rarely
      reported. Endobronchial actinomycosis can be misdiagnosed as unresolving
      pneumonia, endobronchial lipoma or malignancies. Endobronchial actinomycosis
      should be included in the differential diagnosis of any endobronchial mass. We
      report a case of a 43-year-old man who presented with a productive cough and
      pulmonary consolidation at the right lower lobe on chest radiograph. Fiberoptic
      bronchoscopy revealed obstruction of the right superior segment of the lower
      bronchus with an exophytic endobronchial mass. Endobronchial actinomycosis was
      confirmed by demonstration of sulfur granules in the bronchoscopic biopsy of the
      mass. Intravenous administration of penicillin G followed by oral
      amoxacillin/clavulanic acid therapy for 3 months resulted in improving symptoms.
      Infiltrative consolidation on the chest X-ray was markedly decreased.

PMID- 11242815
TI  - A case of primary intestinal T-cell lymphoma involving entire gastrointestinal
      tract: esophagus to rectum.
AB  - Primary intestinal T-cell lymphoma is a rare disease entity, which is
      approximately 10% to 25% of intestinal lymphomas, and most of the lymphomas occur
      in the small intestine. We report here a case of a 56-year-old woman who has been
      suffering from chronic diarrhea and weight loss for 6 months. Abdominal CT scan
      and small bowel series showed diffuse wall thickening of the small bowel.
      Gastroscopic examination showed diffuse erythematous lesions on the esophagus and
      small gastric ulcerations on the antrum of the stomach, and colonoscopic
      examination also showed multiple punched-out ulcerations and erosions on the
      entire colon, including the sigmoid colon to the terminal ileum. Diffuse
      infiltration of CD 3 positive lymphoma cells was found on biopsy. The patient was
      diagnosed as primary intestinal T-cell lymphoma with diffuse involvement of the
      entire gastrointestinal tracts from the esophagus to the rectum. Although the
      patient received systemic combination chemotherapy and achieved partial response
      initially, the lymphoma relapsed repeatedly.

PMID- 11242816
TI  - Active surveillance for acute flaccid paralysis in poliomyelitis high-risk areas
      in southern China.
AB  - OBJECTIVE: On 29 October 2000 poliomyelitis was officially declared to have been
      eradicated from the Western Pacific Region. This article describes the results of
      surveillance for cases of acute flaccid paralysis (AFP) in China during the final
      phase of the eradication effort. METHODS: We conducted hospital-based active
      surveillance in high-risk areas for poliomyelitis in 5 provinces of southern
      China (Sichuan, Yunnan, Guizhou, Guangxi and Jiangxi) between 1995 and 1997 to
      determine the adequacy of reporting and laboratory diagnosis of cases of AFP.
      FINDINGS: A total of 1069 AFP cases occurring since 1993 were identified in 311
      hospital visits. Less than 50% of AFP cases occurring in 1993 and 1994 had been
      reported by AFP surveillance, and laboratory diagnosis had been carried out on
      only a small proportion of these. However, improved cooperation between hospital
      sectors increased the rate of case reporting and laboratory diagnosis to 85% and
      78%, respectively, in 1997. Despite this overall improvement, these two
      indicators were approximately 10-20% lower in Yunnan Province. Epidemiological
      analysis revealed that cases of clinical poliomyelitis accounted for as much as
      one-third of all AFP in 1993 and that some of these cases were clustered.
      Clusters were rarely observed after 1994. Active surveillance in the China
      Myanmar border areas of Yunnan over 1995-96 detected 9 cross-border cases of
      clinical poliomyelitis, including 2 of wild poliomyelitis. Import of
      poliomyelitis was thus considered to have occurred frequently until 1996 in this
      border area of Yunnan. These data were important for the outbreak response
      immunization carried out in 1996 in the border prefectures of Yunnan. CONCLUSION:
      Our investigation confirmed a high level of AFP surveillance in poliomyelitis
      high-risk areas of the five provinces and provided valuable information on the
      interruption of wild poliovirus circulation in southern China that will be of use
      to countries in other regions that have yet to eradicate poliomyelitis.

PMID- 11242817
TI  - Local problems, local solutions: improving tuberculosis control at the district
      level in Malawi.
AB  - OBJECTIVE: To examine the causes of a low cure rate at the district level of a
      tuberculosis (TB) control programme and to formulate, implement, and evaluate an
      intervention to improve the situation. METHODS: The study setting was Mzuzu
      (population 60,000), where the annual smear-positive pulmonary TB incidence was
      160 per 100,000 and the human immunodeficiency virus (HIV) seroprevalence was 67%
      among TB patients. There is one TB treatment unit, but several other
      organizations are involved with TB control. An examination of case-holding
      activities was carried out, potential areas for improvement were identified, and
      interventions performed. FINDINGS: In 1990-91, the cure rate was 24% among smear
      positive cases (29% among survivors to end of treatment). Problems identified
      included a fragmented TB control programme; inadequate training and supervision;
      suboptimal recording of patients' addresses; and nonadherence to national TB
      control programme protocols. These problems were addressed, and in 1992-93 the
      cure rate rose to 68% (relative risk (RR) = 2.85 (95% confidence interval (CI) =
      1.63, 4.96)) and to 92% among survivors to the end of treatment (RR = 3.12 (95%
      CI = 1.84, 5.29)). High cure rates are therefore achievable despite high HIV
      prevalence. CONCLUSIONS: Simple, inexpensive, local programmatic interventions
      can dramatically improve TB case holding. This study demonstrates the need for
      evaluation, training, and supervision at all levels of the programme.

PMID- 11242818
TI  - Etiology of urethral discharge in West Africa: the role of Mycoplasma genitalium
      and Trichomonas vaginalis.
AB  - OBJECTIVE: To determine the etiological role of pathogens other than Neisseria
      gonorrhoeae and Chlamydia trachomatis in urethral discharge in West African men.
      METHODS: Urethral swabs were obtained from 659 male patients presenting with
      urethral discharge in 72 primary health care facilities in seven West African
      countries, and in 339 controls presenting for complaints unrelated to the
      genitourinary tract. Polymerase chain reaction analysis was used to detect the
      presence of N. gonorrhoeae, C. trachomatis, Trichomonas vaginalis, Mycoplasma
      genitalium, and Ureaplasma urealyticum. FINDINGS: N. gonorrhoeae, T. vaginalis,
      C. trachomatis, and M. genitalium--but not U. urealyticum--were found more
      frequently in men with urethral discharge than in asymptomatic controls, being
      present in 61.9%, 13.8%, 13.4% and 10.0%, respectively, of cases of urethral
      discharge. Multiple infections were common. Among patients with gonococcal
      infection, T. vaginalis was as frequent a coinfection as C. trachomatis. M.
      genitalium, T. vaginalis, and C. trachomatis caused a similar clinical syndrome
      to that associated with gonococcal infection, but with a less severe urethral
      discharge. CONCLUSIONS: M. genitalium and T. vaginalis are important etiological
      agents of urethral discharge in West Africa. The frequent occurrence of multiple
      infections with any combination of four pathogens strongly supports the syndromic
      approach. The optimal use of metronidazole in flowcharts for the syndromic
      management of urethral discharge needs to be explored in therapeutic trials.

PMID- 11242819
TI  - Situation analysis for cervical cancer diagnosis and treatment in east, central
      and southern African countries.
AB  - OBJECTIVE: To determine the factors influencing cervical cancer diagnosis and
      treatment in countries of East, Central and Southern Africa (ECSA). METHODS: Data
      were collected from randomly selected primary health care centres, district and
      provincial hospitals, and tertiary hospitals in each participating country.
      Health care workers were interviewed, using a questionnaire; the facilities for
      screening, diagnosing, and treating cervical cancer in each institution were
      recorded, using a previously designed checklist. FINDINGS: Although 95% of
      institutions at all health care levels in ECSA countries had the basic
      infrastructure to carry out cervical cytology screening, only a small percentage
      of women were actually screened. Lack of policy guidelines, infrequent supply of
      basic materials, and a lack of suitable qualified staff were the most common
      reasons reported. CONCLUSIONS: This study demonstrates that there is an urgent
      need for more investment in the diagnosis and treatment of cervical cancer in
      ECSA countries. In these, and other countries with low resources, suitable
      screening programmes should be established.

PMID- 11242820
TI  - Changing causes of death in the West African town of Banjul, 1942-97.
AB  - OBJECTIVE: To determine trends in the causes of death in a West African town.
      Mortality caused by infectious diseases is reported to be declining while
      degenerative and man-made mortality factors are increasingly significant. Most
      mortality analyses for sub-Saharan Africa have involved extrapolation and have
      not been derived from community-based data. METHODS: Historical data on causes of
      death coded by physicians were analysed for the urban population of Banjul for
      the period 1942-97. As the calculation of rates is not possible in the absence of
      a reliable population denominator, age-standardized proportional mortality ratios
      (PMRs) for men and women by major groups of causes of death were calculated,
      using the 1942-49 data for reference purposes. FINDINGS: Most deaths were
      attributable to communicable diseases. There was a shift in proportional
      mortality over the study period: the contribution of communicable diseases
      declined and that of noncommunicable diseases and injuries increased. These
      trends were more marked among men than women. CONCLUSION: The data illustrate
      that while noncommunicable diseases and injuries are emerging as important
      contributors to mortality in sub-Saharan Africa, communicable diseases remain
      significant causes of mortality and should not be neglected.

PMID- 11242821
TI  - Coping with changing conditions: alternative strategies for the delivery of
      maternal and child health and family planning services in Dhaka, Bangladesh.
AB  - The door-to-door distribution of contraceptives and information on maternal and
      child health and family planning (MCH-FP) services, through bimonthly visits to
      eligible couples by trained fieldworkers, has been instrumental in increasing the
      contraceptive prevalence rate and immunization coverage in Bangladesh. The
      doorstep delivery strategy, however, is labour-intensive and costly. More cost
      effective service delivery strategies are needed, not only for family planning
      services but also for a broader package of reproductive and other essential
      health services. Against this backdrop, operations research was conducted by the
      Centre for Health and Population Research at the International Centre for
      Diarrhoeal Disease Research, Bangladesh (ICDDR,B) from January 1996 to May 1997,
      in collaboration with government agencies and a leading national nongovernmental
      organization, with a view to developing and field-testing alternative approaches
      to the delivery of MCH-FP services in urban areas. Two alternative strategies
      featuring the withdrawal of home-based distribution and the delivery of basic
      health care from fixed-site facilities were tested in two areas of Dhaka. The
      clinic-based service delivery strategy was found to be a feasible alternative to
      the resource-intensive doorstep system in urban Dhaka. It did not adversely
      affect programme performance and it allowed the needs of clients to be addressed
      holistically through a package of essential health and family planning services.

PMID- 11242822
TI  - Low-cost on-the-job peer training of nurses improved immunization coverage in
      Indonesia.
AB  - In Indonesia responsibility for immunizations is placed on local government
      health centres and on the nurses who provide the immunizations at each centre. An
      on-the-job peer training programme for these nurses, which was designed to
      improve the immunization performance of poorly performing health centres in terms
      of coverage and practice in Maluku province, was evaluated. Experienced
      immunization nurses were sent to health centres where nurses were inexperienced
      or performing poorly; the experienced nurses spent 1-2 weeks providing on-the-job
      training for the less experienced ones. An evaluation of the 13 centres that
      participated in the programme and the 95 that did not found that the programme
      increased both immunization coverage and the quality of practice. Coverage of
      diphtheria/pertussis/tetanus (DPT), polio, and measles vaccinations rose by about
      39% in all 13 participating centres when compared with non-participating centres,
      and by about 54% in the 11 centres that had a functioning transportation system
      during the year after training. These results reflect increases in the actual
      number of doses given and improvements in the accuracy of reports. Potential
      threats to the study's validity were examined and found not to be significant.
      The out-of-pocket cost of the training programme was about US$ 53 per trainee or
      about US$ 0.05 per additional vaccine reported to have been given. The marginal
      cost per additional fully immunized child was estimated to be US$ 0.50.

PMID- 11242823
TI  - Population health in transition.

PMID- 11242824
TI  - Homicide among adolescents in the Americas: a growing epidemic.

PMID- 11242825
TI  - Elevated blood lead levels in Karachi children.

PMID- 11242826
TI  - Making medicines safe.

PMID- 11242827
TI  - Diethylene glycol poisoning in Gurgaon, India, 1998.
AB  - OBJECTIVE: To discover the cause of acute renal failure in 36 children aged 2
      months to 6 years who were admitted to two hospitals in Delhi between 1 April and
      9 June 1998. METHODS: Data were collected from hospital records, parents and
      doctors of the patients, and district health officials. Further information was
      obtained from house visits and community surveys; blood and stool samples were
      collected from other ill children, healthy family members and community contacts.
      Samples of drinking-water and water from a tube-well were tested for coliform
      organisms. FINDINGS: Most of the children (26/36) were from the Gurgaon district
      in Haryana or had visited Gurgaon town for treatment of a minor illness. Acute
      renal failure developed after an episode of acute febrile illness with or without
      watery diarrhoea or mild respiratory symptoms for which the children had been
      treated with unknown medicines by private medical practitioners. On admission to
      hospital the children were not dehydrated. Median blood urea concentration was
      150 mg/dl (range 79-311 mg/dl) and median serum creatinine concentration was 5.6
      mg/dl (range 2.6-10.8 mg/dl). Kidney biopsy showed acute tubular necrosis. Thirty
      three children were known to have died despite being treated with peritoneal
      dialysis and supportive therapy. CONCLUSION: Cough expectorant manufactured by a
      company in Gurgaon was found to be contaminated with diethylene glycol (17.5%
      v/v), but a sample of acetaminophen manufactured by the same company tested
      negative for contamination when gas-liquid chromatography was used. Thus,
      poisoning with diethylene glycol seems to be the cause of acute renal failure in
      these children.

PMID- 11242828
TI  - Awareness of eye diseases in an urban population in southern India.
AB  - OBJECTIVE: To assess the level of awareness of eye diseases in the urban
      population of Hyderabad in southern India. METHODS: A total of 2522 subjects of
      all ages, who were representative of the Hyderabad population, participated in
      the population-based Andhra Pradesh Eye Disease Study. Of these subjects, 1859
      aged > 15 years responded to a structured questionnaire on cataract, glaucoma,
      night blindness and diabetic retinopathy to trained field investigators. Having
      heard of the eye disease in question was defined as "awareness" and having some
      understanding of the eye disease was defined as "knowledge". FINDINGS: Awareness
      of cataract (69.8%) and night blindness (60.0%) was moderate but that of diabetic
      retinopathy (27.0%) was low, while that of glaucoma (2.3%) was very poor.
      Knowledge of all the eye diseases assessed was poor. Subjects aged > or = 30
      years were significantly more aware of all eye diseases assessed except night
      blindness. Multivariate analysis revealed that women were significantly less
      aware of night blindness (odds ratio (OR) = 0.78; 95% confidence interval (CI) =
      0.63-0.97). Education played a significant role in awareness of these eye
      diseases. Study subjects of upper socioeconomic status were significantly more
      aware of night blindness (OR = 2.20; 95% CI = 1.29-3.74) and those belonging to
      upper and middle socioeconomic strata were significantly more aware of diabetic
      retinopathy (OR = 2.79; 95% CI = 2.19-3.56). Muslims were significantly more
      aware of cataract (OR = 2.36; 95% CI = 1.84-3.02) and less aware of night
      blindness (OR = 0.52; 95% CI = 0.42-0.64). The major source of awareness of the
      eye diseases was a family member/friend/relative suffering from that eye disease.
      CONCLUSION: These data suggest that there is a need for health education in this
      Indian population to increase their level of awareness and knowledge of common
      eye diseases. Such awareness and knowledge could lead to better understanding and
      acceptance of the importance of routine eye examinations for the early detection
      and treatment of eye diseases, thereby reducing visual impairment in this
      population.

PMID- 11242829
TI  - [Pharmaceutical importance of Allium sativum L. 1. Organic sulfur compounds and
      their transformation based on present knowledge].
AB  - The paper sums up new experimental knowledge concerning the individual groups of
      organic sulfurous substances of the garlic: sulfoxides, thiosulfinate, ajoens,
      vinyldithiines, alkyl and alkene sulfides and glutamylpeptides of sulfurous amino
      acids, their transformation reactions (based on the temperature, pH, extraction
      medium, and time) and the final products of transformations (Scheme 1, 2). It
      deals with the activity of the enzyme alliinase necessary for the transformation
      of sulfoxides present in the whole garlic, its isolation and stability as well as
      the stability of the dominant thiosulfinate allicin in various media and
      simulated body fluids. It refers to the studies of the metabolism and
      transformations of the most important sulfurous components performed in vitro on
      the hepatocytes and on the isolated rat liver, and those carried out in vivo on
      the rats and including the examination of the composition of the exhaled air. It
      follows from published papers that all different degradation products of
      thiosulfinates, mainly the prevailing allicin, are carriers of various biological
      activities. The paper also lists the types of commercial preparations prepared
      from the garlic, their differences, and considerable variability of their
      contents of active principles.

PMID- 11242830
TI  - [A review of radiodiagnosis of inflammations].
AB  - Inflammation is a complex reaction of the organism which develops as a response
      to invasion of an infectious subject or as a response to injury to cells or
      tissues. Correct and early localization of infection or an inflammatory lesion
      allows removing the inflammatory cause quickly. Over the recent thirty years, a
      wide range of radiopharmaceuticals, more or less applicable in scintigraphic
      imaging of inflammatory and infectious diseases, have been developed. The aim has
      been to develop new substances that are non-toxic, do not provoke immune
      reactions, and produce a minimal absorbed radioactive dose. Furthermore, these
      substances should accumulate significantly in the target tissue (i.e. in
      inflammation), while the accumulation in non-target tissues should be minimal or
      the elimination of radiopharmaceuticals from non-target tissues must be quick.
      The goal is that these substances may also be easily available and inexpensive.
      Another purpose is to develop such substances that could possess not only
      sufficient sensitivity but also specificity in relation to certain types of
      inflammation and infection. The main indications for radionuclide imaging are as
      follows: inflammatory bowel disease, soft tissue sepsis, predominantly abdominal
      sepsis, musculoskeletal infection, and fever of unknown origin.

PMID- 11242831
TI  - [Use of synthetic biodegradable polymers in medicine].
AB  - Synthetic biodegradable polymers, such as polyesters, polyanhydrides,
      polyorthoesters, polycarbonates, polyphosphoesters, polyphosphazenes,
      polyesteramides, polyalkylenoxalates, polyalkylcyanoacrylates, etc., are
      represented as materials which are being tested for use, or which have been
      already used in surgery, orthopaedics, and pharmacy. A particular attention is
      devoted to their use in the preparation of systems with prolonged release or with
      targeted biodistribution of active ingredients.

PMID- 11242832
TI  - [Calorimetric evaluation of directly compressed tablets].
AB  - The paper studies the effect of the type of the disintegrating substance and the
      lubricant on the destruction heat of tablet materials and tablets. Destruction
      heat was determined by means of isoperibolic calorimetry. Tablet materials and
      tablets contained Avicel PH 101 as the dry binder, 10% of Primojel, Ac-Di-Sol, or
      Polyplasdone XL as disintegrating substances, and 5% of magnesium strearate or
      sodium laurylsulfate as the lubricants. The sum of destruction heats of the
      individual auxiliary substances equalled the found values in tablet materials and
      tablets. In tablets, in contrast to tablet materials, values of destruction heat
      higher by 57.9% were found. In the disintegrating substances and lubricants
      tested, the found values of destruction heats were dependent on the values of
      destruction heats of the individual auxiliary substances. In the disintegrating
      substances, a linear dependence of the total destruction heat (CDT) on the
      destruction heat of the disintegrating substances (DTR) was found, given by the
      relationship CDT = 0.797.DTR + 17.666 with the correlation coefficient r = 0.986.

PMID- 11242833
TI  - [Prednicarbate and cetirizin dihydrochloride in the treatment of atopic eczema in
      the acute phase in children].
AB  - The aim of the study was to monitor the impact of local application of
      prednicarbat (Dermatop, Hoechst-Biotika) and oral administration of cetirizin
      (Zyrtec, UCB) on the development of the acute stage of atopic eczema (AE) or
      acute exacerbation of the chronic form of AE in two groups of patients.
      Effectiveness and safety of both preparations were being evaluated in 80 children
      undergoing an outpatient treatment. In the first group, only prednicarbat cream
      was applied to affected places twice a day for a maximum of 10 days, while in the
      other group also cetirizin was administered once a day in a dosage according to
      the patient's age. On the treated places, erythema, infiltrate and excoriation
      were evaluated with respect to the intensity of manifestation. The results of the
      study show favourable effects of both preparations on AE development, already
      during the first days of the therapy. In both groups there was a complete
      remission of the monitored symptoms in more than 80 per cent of the patients.
      There was no deterioration of the disease in any patient, and no cases of adverse
      reactions were registered.

PMID- 11242834
TI  - [Development of chemotherapy in tuberculosis].
AB  - The paper belongs to the series of review papers entitled "Substances with
      Antituberculous Effects". In contrast to other communications of the series, it
      deals with the present state of tuberculosis and the development of its
      chemotherapy. Whereas the other review papers of the series survey the
      development of structures of novel potential drugs, the present paper aims to
      show possible treatment of tuberculosis and its problems, concentrating on the
      contemporary situation.

PMID- 11242835
TI  - [Effect of the biotic elicitor, Candida utilis, on the production of anthracene
      derivatives in a tissue culture of Rheum palmatum L].
AB  - The paper studied the effect of the homogenate of Candida utilis on the
      production of anthracene derivatives by the callus and suspension culture of
      Rheum palmatum L. of different age and origin. The culture was cultivated on a
      Murashige-Skoog medium with an addition of 10 mg.l-1 of alpha-naphthylacetic
      acid. A positive effect on the production was caused mainly by the elicitation of
      the suspension culture. The maximal content of anthracene derivatives (1.346%),
      found by photometric determination according to PhBs 4, was demonstrated after 6
      hour action of the homogenate of Candida utilis of a concentration of 0.143 mg/30
      ml of the medium in an eight-year old culture derived from the root of the intact
      plant Rheum palmatum. A one-year-old culture derived from the root of the intact
      and germinating plant reacted to elicitation more sensitively as there was an
      increase in production up to 228% in comparison with the control. However, the
      content of anthracene derivatives was lower than in the eight-year-old culture.
      In contrast to the suspension culture, the production of anthracene derivatives
      in the callus culture was influenced by elicitation only in the minimal extent.

PMID- 11242836
TI  - [The content and quality of Melissa officinalis essential oil after application
      of Rastim 30 DKV].
AB  - The paper deals with the evaluation of the content and quality of the essential
      oil of Melissa officinalis in various leaf insertions in the course of the
      ontogenetic development of the plant. The quality of the drug after the
      administration of the preparation Rastin 30 DKV in the form of granules was not
      changed in comparison with control samples. The experimental work, subsequent
      analysis of samples, and evaluation of results led to conclusions important from
      the viewpoint of significant changes in the content and composition of the
      essential oil taking place in the plant in the course of the vegetation period.

PMID- 11242837
TI  - [Polyphenol compounds from Hamamelis virginiana L].
AB  - Two phenolic acids and two flavone aglycones were isolated from the aboveground
      part of Hamamelis virginiana L. and identified with the use of thin-layer
      chromatography, melting points, and spectroscopic methods as gallic acid, ethyl
      gallate, quercetin, and kaempferol.

PMID- 11242838
TI  - Atrial fibrillation. An uneven rhythm.

PMID- 11242839
TI  - Health tips. Nondrug help for high blood pressure.

PMID- 11242840
TI  - Multifocal lens implants aren't problem-free [news].

PMID- 11242841
TI  - New cream to treat skin cancer? [news].

PMID- 11242842
TI  - Myelodysplastic syndrome. When blood cell production goes wrong.

PMID- 11242843
TI  - Breast cancer and hot flashes. Options for relief.

PMID- 11242844
TI  - Exotic diseases. Are they spreading to a town near you?

PMID- 11242846
TI  - I've been having problems controlling my bowels and have had some "accidents"
      lately. Is this common? Can it be helped?

PMID- 11242845
TI  - I have diabetes. Sometimes, I'm troubled by hypoglycemia. What can I do to avoid
      it?

PMID- 11242847
TI  - [Morphological characteristics of heart conduction system in diphtheria].
AB  - Heart conductive system (HCS) including the sinoatrial node (SAN),
      atrioventricular node (AVN), AV bundle (AVB) and its left and right parts was
      studied histologically. It is shown that different portions of HCS are damaged in
      diphtheria with different frequency and intensity, the frequency depending on the
      depth of their location. Left part of AVB is affected most frequently, followed
      by the right part of AVB, AVB, AVN and the least frequently SAN.

PMID- 11242848
TI  - [Characteristic of proliferative processes in colonic mucosa in acute
      salmonellosis].
AB  - DNA synthesis in the epithelium of a distal portion of human colon was studied at
      radioautography with 3H-thymidine through the first three days of
      gastrointestinal salmonellesis. Control studies were performed on the mucosa of
      the sigmoid colon of healthy persons undergoing rectoromanoscopy because of
      epidemiological reasons. No pathological changes were found in these specimens,
      the labeled nuclei index (LNI) was 5.16 +/- 0.27%, the label intensity (LI) which
      characterizes the rate of DNA synthesis was 13.65 +/- 0.82. Group 1 consisted of
      18 patients having slight inflammation without erosions, ulcerative and
      haemorrhagic changes. We found significant activation of proliferation (LNI =
      15.09 +/- 0.9%, LI = 22.23 +/- 1.9; p < 0.05) in this group compared to the
      control one. 15 patients with salmonella-induced hemorrhagic colitis formed group
      2 in which LNI and LI were also increased (LNI = 9.89 +/- 1.0%, LI = 19.3 +/-
      2.3; p < 0.02) vs. control group, but these changes seemed to be significantly
      weaker than those in group 1 (p < 0.01). It is inferred that rates of
      proliferation in colon epithelium in acute salmonellosis are significantly higher
      than in healthy epithelium but activity of these processes decreases with growing
      severity of inflammation.

PMID- 11242850
TI  - [Clinical-pathologoanatomic analysis of post-operative thromboembolism of
      pulmonary artery].
AB  - Autopsy and clinical data were analysed for 803 surgical patients whose death was
      due to pulmonary artery thromboembolism (PAT). PAT was diagnosed intravitally in
      32% of the deceased. 87% of the patients with PAT symptoms died within 2 hours.
      3/4 of PATs developed in uneventful postoperative period, 1/4--in complications.
      The cause of PAT in 99.3% of cases were thromboses in vena cava inferior. In
      88.3% of cases these thromboses ran latently. Frequency of postoperative PAT as a
      cause of death was 1.4% in 1972-1973, 2.1% in 1990-1991, 1.3% in 1997. The fall
      of the death rate is explained by introduction of drug prophylaxis of PAT.

PMID- 11242849
TI  - [On the problem of pathomorphosis of modern tick-borne encephalitis in Ural].
AB  - Pathology study of 32 patients who died of tick-borne encephalitis (TBE) in the
      Ural Region in 1990s revealed differences with this infection registered in 1940
      1950s. Pathological changes in the central nervous system by their severity and
      location are like those observed in the Far East TBE. Apart from grave alterative
      changes in the nerve cells of motor nuclei of the spinal cord and brain, three
      types of pathological changes are observed: productive inflammation, exudative
      inflammation without pronounced inflammatory reaction. Differences in the
      organism reactions to the infectious process are explained by differences in the
      virus virulence and organism immunological status.

PMID- 11242851
TI  - [Lymphoproliferative diseases of the orbit and appendages of the eye].
AB  - The results are available of clinical, morphological, cytological and
      immunological investigations of orbital lymphomas and lymphomas of appendages of
      the eye. Malignant lymphoma was detected in 17 patients and reactive lymphoid
      hyperplasia in 3 patients. All the malignant lymphomas had B-cell phenotype. By
      cell composition, MALT-lymphoma is more polymorphic than lymphoma from mantle
      zone cells and lymphoma from small lymphocytes and centro follicular lymphoma.
      The conjunctive is affected primarily with lymphoma from marginal zone cells or
      mantle zone cells. As a rule, this is a primary local lesion. Other variants of
      orbital lymphoma and lymphoma of the eye appendages develop more often as
      secondary lesions in systemic disease and are characterized by more aggressive
      course. The key in differential diagnosis of reactive lymphoid hyperplasia and
      small cells lymphomas is immunophenotyping, especially at initial stages of the
      tumor process.

PMID- 11242852
TI  - [From Virchow's cellular pathology to modern molecular pathology].
AB  - Evolution of Virchow's cellular pathology into molecular biology and molecular
      pathology due to achievements of cytology, biochemistry (histochemistry),
      immunology (immunomorphology) and genetics as well as new opportunities opened by
      integration of these disciplines (electron histochemistry, immunohistochemistry,
      immunogenetics, etc.).

PMID- 11242853
TI  - [Mechanism of collagen resorption in uterine postpartum involution].
AB  - Extracell and intracell mechanisms of collagen resorption were revealed electron
      histochemically in the uterus of rats in its postnatal involution. Cathepsin B
      secreted mainly by smooth muscle cells as well as by macrophages and fibroblasts
      into the intracellular space takes an active part in the extracellular collagen
      resorption. Simultaneously with intensive extracellular lysis of collagen in the
      uterus there is phagocytosis and intracellular collagen resorption (due to
      cathepsin B and other lysosomal proteinases) by macrophages and fibroblasts and,
      to a lesser extent, by smooth muscle cells.

PMID- 11242854
TI  - [A fatal outcome of false croup in lacunar angina complicated by peritonsillar
      abscess].
AB  - The paper reports a lethal outcome of false croup in a 62-year-old man. In
      pathogenetic chain of the disease the leading role belonged to purulent
      tonsillitis with peritonsillar abscess and epiglottitis with phlegmone of the
      adjacent soft tissues including the vocal cords. A severe edema of the latter
      provoked a complete obstruction in the larynx and asphyxia with all its macro-
      and microscopic morphological features. Chronic alcoholic intoxication seemed to
      cause immunodeficiency and slow progression of the disease. Tonsillitis, chronic
      with exacerbation, was alleviated by chronic alcoholic intoxication leading to
      weak symptoms, delayed reactions and "strange" outcome. Hyperergia could be due
      to intake of alcohol surrogate.

PMID- 11242855
TI  - [Cladosporiosis in chronic herpetic encephalomyelitis].
AB  - One case of chronic herpetic meningoencepalitis complicated by a rare my costs of
      the central nervous system (CNS) and generalised viral infection is described.
      Cladosporiosis is considered as a lesion resulting from a immunosuppression due
      to chronic herpetic involvement of CNS. Morphologically this mycosis is
      manifested by the presence of spors and septic micelium among cells of productive
      inflammation an inside of giant multinuclear cells in affected areas. Viral
      nature of the encephalomyelitis is documented by presence of typical intranuclear
      inclusions and detection of herpetic antigen by means of fluorescent antibodies.

PMID- 11242856
TI  - [Aspergillosis (mycetoma) of gluteal region].
AB  - Lingering deep gluteal mycosis (mycetoma, aspergillosis) in a 32-year-old woman
      with secondary immunodeficiency is described. The disease developed after
      intragluteal injection of vitamins and was characterized by development of
      multiple dense nodes in the skin and soft tissues, parametral and pararectal fat
      tissue with repeated fistulas. The diagnosis was established by finding fungi
      histologically and cytologically.

PMID- 11242857
TI  - [80 years anniversary of Department of Pathology of the I Tashkent State Medical
      Institute].

PMID- 11242858
TI  - [Chronic and slow neuroinfections. Current status of problem].
AB  - Some causes and conditions of chronic and slow neuroinfections were reviewed:
      brain immunological "priveledge"; congenital immunodeficiencies including
      clinically latent; immunomodulation induced by microorganisms due to infection of
      immune cells, inactivation of cytokines making difficulties to antibodies;
      disorders of genetic control of immune reaction; immunopathologic processes are
      of great importance for the agents persistence including autoimmunity.
      Microorganisms can locate in the neurons, glyocytes, endothelium. Neuroinfections
      chronic course depends on the agents properties and peculiarities of nervous
      system reactivity.

PMID- 11242859
TI  - [Molecular mechanisms of apoptosis pathology].
AB  - Apoptosis--a programmed cell death--is a general biological mechanism responsible
      for maintenance of a permanent cell number. Impairment of apoptosis regulation
      entails disorders in homeostasis and various diseases. This explains biological
      and medical importance of apoptosis. Molecular grounds of apoptosis regulation,
      physiological regulation depending on the cell type, examples of apoptosis
      disregulation leading to definite diseases, approaches to treatment of some
      diseases basing on knowledge of apoptosis regulation are provided.

PMID- 11242860
TI  - [Comparative characteristics of granulomatous inflammation in sarcoidosis and
      tuberculosis].
AB  - Comparisons are given of clinical manifestations and pathomorphological changes
      in lymph nodes and lungs of 76 patients with sarcoidosis and 48 patients with
      tuberculosis. Two types of tissue reactions were shown: with minimal and marked
      fibrosis. The former type is characterized by high density of granulomatosis and
      low density of fibrosis, large granulomas which contained many giant cells. The
      latter type is characterized by advanced fibrosis, small granulomas with rare
      giant cells. For clinically marked sarcoidosis, tissue reaction with predominant
      granulomatosis is typical, for patients with scare symptoms--tissue reaction with
      evident fibrosis. In the absence of caseous necrosis, differential diagnosis
      between tuberculosis and sarcoidosis with prevalent granulomatosis is impossible
      by morphological picture and morphometric evidence.

PMID- 11242861
TI  - [Are all new methods in health care to be freely implemented?].

PMID- 11242862
TI  - [Life and health of adolescents].

PMID- 11242863
TI  - [What does the high frequency of attention disorders and hyperactivity among
      children with low birth weight mean?].

PMID- 11242864
TI  - [Ulcerative colitis].

PMID- 11242865
TI  - [Asthma, steroid inhalation and growth].

PMID- 11242866
TI  - [Day care centers, infections and asthma].
AB  - BACKGROUND: Our objective was to use a causal model for childhood asthma to
      determine whether the effect of day care attendance on asthma was mediated by
      recurrent respiratory tract infections. MATERIAL AND METHODS: The study is based
      on a cross-sectional survey among 1,447 children aged 6-16 years in Oslo. Their
      parents completed written questionnaires. A recursive logit model was used to
      estimate direct effects in terms of adjusted odds ratios (aOR). RESULTS: Year of
      birth, number of siblings and length of maternal education were significantly
      associated with after-school care attendance. Attendance increased the risk of
      early infections, aOR = 1.8 (1.3-2.5), and infections were associated with
      asthma, aOR = 4.9 (3.4-7.3). The crude association between after-school care and
      asthma was cOR = 1.5 (1.0-2.2), whereas the estimated direct effect was small and
      non-significant, aOR = 1.2 (0.8-1.9). The results may be influenced by over
      reporting of infections among parents with children with asthma. INTERPRETATION:
      Our results suggest that children who attend day care have an increased risk of
      asthma, with early infections as a mediator of risk.

PMID- 11242867
TI  - [Adolescents living on their own--social control and health related behavior].
AB  - BACKGROUND AND OBJECTIVES: Social control is an important dimension in the
      interaction between members of social groups. Such control may contribute to
      adherence to group norms and prevent health related risk behaviour. Adolescents
      moving out from home to live on their own may become left to themselves and lose
      their social network and mechanisms of control. We wanted to examine to what
      extent high school students living in lodgings were different from students
      living at home concerning health and health related behaviour. MATERIAL AND
      METHODS: The study was based on data from a cross sectional inquiry among 828
      high school students (91% of all students) in Forde carried out in 1997. One in
      four students lived alone in bedsitters. Bivariate analyses were performed
      separately for the two age groups 15-17 and over 18 years of age. Students living
      on their own were compared with students living at home concerning self-reported
      health and health behaviour. Multivariate analyses were performed to control for
      confounding. RESULTS: Students living in bedsitters more often reported health
      risk behaviour than their home-living peers. The differences was most conspicuous
      in the youngest age group. Differences were found for cigarette smoking, alcohol
      use, unhealthy diet, and age of sexual debut. Health-risk behaviour was most
      prevalent among students in vocational courses living alone. Self-reported health
      and emotional wellbeing were as good among students living alone as it was among
      their home-living peers. CONCLUSION: Reduction of social control among students
      living alone in lodgings seem correlated with increased health risk behaviour.
      Students in vocational courses may be at particular risk. Social planning of
      education should consider the need to belong and the need for new social networks
      among students leaving home to continue their education.

PMID- 11242868
TI  - [Functional outcome after reservoir surgery in ulcerative colitis].
AB  - BACKGROUND: The aim of this study was to examine whether the functional result of
      restorative proctocolectomy for ulcerative colitis deteriorated by postponing
      follow-up from three to eight years after pouch surgery. MATERIAL AND METHODS:
      All patients (n = 58) operated for ulcerative colitis from 1984-97, who still had
      intact reservoir, responded to a questionnaire on defecating pattern, stool
      leakage, perianal irritation, urinary function, workload, sexual life, social
      life, and the patient's opinion on outcome. The results for the first 29 patients
      were compared to last 29 patients operated. Median follow-up was eight for the
      first 29 patients and three years for the last 29. RESULTS: There were no
      significant difference in functional outcome and patient opinion after pouch
      surgery between the first 29 and last 29 patients (n = 58). Respective figures
      for median 24-hour stool frequency were 7.0 and 6.3, leakage of stool 48% and
      38%, ability to defer defecation 86% and 97%, perianal irritation 59% and 48%,
      use of antidiarrhoeal medication 55% and 52%, and wearing of pad 28% and 38%.
      Sexual life (n = 57) had improved for 11 (19%) and deteriorated for seven
      patients (12%). Potency was reduced in five (15%) and ejaculation in four
      patients (12%), one of whom (3%) had retrograde ejaculation. Three (5%) had
      received a disability pension and five (9%) had reduced workload. After the pouch
      operation 48 (91%) felt better and three (6%) felt worse because of frequent
      bowel emptying (n = 3), perianal eczema (n = 1) and pouch fistula (n = 1).
      INTERPRETATION: The results do not demonstrate any significant deterioration of
      functional outcome after pouch surgery for ulcerative colitis by postoperative
      increase of follow-up from three to eight years.

PMID- 11242869
TI  - [Results after emergency surgery and ileoanal anastomosis in ulcerative colitis].
AB  - BACKGROUND: Patients suffering from severe ulcerative colitis often receive
      emergency colectomy at vital indication. Some of them are offered an ileal pouch
      anal anastomosis a few months later. MATERIAL AND METHODS: All patients (n = 80)
      from May 1985 to August 1998 who were subjected to emergency colectomy at the
      National Hospital of Norway because of severe ulcerative colitis were studied
      prospectively. 40 patients later underwent a successful ileal pouch-anal
      anastomosis operation; 36 of them were sent a questionnaire assessing anal
      function. RESULTS: No patients died during admission or within 30 days of
      emergency colectomy. Five patients (6%) developed postoperative complications
      requiring reoperation. 31 patients returned the questionnaire. All reported full
      bowel control, although two used pads during night. Mean number of evacuations
      per 24 hours was six. 14 patients (45%) usually had evacuations during night. All
      patients would prefer ileal pouch-anal anastomosis if they were given the choice
      between this and permanent ileostomy again. 87% were satisfied with the operation
      result, 10% were moderately satisfied, 3% were not satisfied. INTERPRETATION: The
      results of urgent colectomy are good, and patients aged < 50 may expect good anal
      function after receiving ileal pouch-anal anastomosis.

PMID- 11242870
TI  - [Psychological status at 8-9 years of age in children with birth weight below
      1,501 grams].
AB  - BACKGROUND: Studies have demonstrated that many children with low birth weight
      show signs of developmental disorders. Research and clinical experience indicate
      that gestational age is related to outcome. The aim of the present study was to
      investigate the differential outcome of children with gestational age < or = 28
      weeks and those who were born later. MATERIAL AND METHODS: The sample consisted
      of 104 infants with birth weight < or = 1,500 g (53 girls) who were followed up
      to age eight years, with subsequent testing of school-related achievement at age
      nine years. Well-known instruments to identify developmental disorders and
      learning difficulties were used. RESULTS: The results showed that for the sample
      as a whole, AD/HD was the most prevalent disorder. There was a moderate degree of
      delay in intellectual development and of learning difficulties. In these areas
      there were significant differences in outcome in favour of the group with
      gestational age > 28 weeks. No significant sex differences were found, except in
      relation to mathematical skills, where boys performed better than girls.
      INTERPRETATION: As a group the children with very low birth weight had adequate
      intellectual and scholastic outcome. However, the prevalence of AD/HD was
      relatively high (27%). Low gestational age, but not dysmaturity, was associated
      with increased risk for poorer outcome.

PMID- 11242871
TI  - [Pyelonephritis in children--a retrospective study].
AB  - BACKGROUND: Urinary tract infection (UTI) is a common bacterial infection in
      childhood, sometimes associated with urological malformations and, in a few
      cases, causing permanent renal damage. MATERIAL AND METHODS: A retrospective
      study was performed of children with UTI first time admitted to Ulleval Hospital
      during the period 1988-97. All medical records with diagnoses related to the
      urinary tract were investigated. Criteria for inclusion were bacteriuria and
      temperature > or = 38.5 degrees C in children over one year of age, and
      bacteriuria below one year of age. RESULTS: Age, sex, symptoms, urine sampling
      method, medical treatment and radiological investigations were evaluated. 180
      children were included, (38% boys, 62% girls), 87% of the boys were referred
      during this first year of life. Fever as sole symptom was found in one of six.
      Urinary tract related symptoms were rare. Urine sampling was performed by
      suprapubic aspiration in only 7%, and was not specified in half of the samples.
      Imaging evaluation was performed in almost all children. More than half of the
      evaluated children had one or more abnormalities, vesicoureteric reflux being the
      most frequent. INTERPRETATION: In our material we find a high frequency of
      urological malformations. Better routines for urine sampling and evaluation of
      long term complications are suggested.

PMID- 11242872
TI  - [Choice of therapy for children with acute gastroenteritis in Norway].
AB  - BACKGROUND: Acute gastroenteritis is a common and potentially lethal condition in
      children worldwide. Recommendations for oral rehydration therapy have been issued
      by paediatric societies both in the USA and Europe. In 1998, The European Society
      of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) initiated a
      multicentre study to determine how current practice corresponds with these
      recommendations. MATERIAL AND METHODS: Paediatricians and general practitioners
      in 29 European countries responded to a questionnaire regarding oral rehydration
      therapy of a six months old infant. RESULTS: In Norway, 55 physicians responded.
      Neither paediatricians nor general practitioners seem to be familiar with all the
      ESPGHAN recommendations. There is a lack of knowledge about the advantages of
      fast rehydration and subsequent early reintroduction of a normal diet. Many
      physicians also wrongly believe that secondary lactose intolerance is a common
      complication. INTERPRETATION: The recommendations do not seem to be well
      implemented among health professionals. It is necessary to educate health-care
      workers at all levels in order to improve treatment of acute diarrhoea in
      children.

PMID- 11242873
TI  - [Fetal circulation--from passive knowledge to current hemodynamics].
AB  - BACKGROUND: Modern technology, especially ultrasound, has made foetal medicine a
      rapidly expanding field. The aim of the present review is to focus at the
      traditional knowledge of foetal circulation, which has recently been reassessed
      and expanded to serve our new patient, the human foetus. MATERIAL AND METHODS:
      Based on literature published mainly over the last 10 years, specific mechanisms
      of the foetal circulation are discussed, particularly the three foetal shunts and
      the placental circuit. RESULTS: The foetal circulation has capacity to compensate
      for considerable cardiovascular abnormalities and to redistribute circulation to
      meet shortage in resources. The circulatory mechanisms described in animal
      foetuses also operate in the human foetus, but with notable differences. The
      ductus venosus shunts 20-30% of the umbilical blood in the human foetus compared
      to 50% in the foetal lamb. The foramen ovale receives less (18-34% of the
      combined cardiac output) and the lungs more blood (13-25%) in the human foetus
      than in the foetal lamb. The isthmus aortae represents a watershed area
      reflecting the redistribution of blood during increased peripheral impedance and
      hypoxemia. INTERPRETATION: The expanded knowledge in human foetal circulation
      promises a more differentiated evaluation than the Doppler examination of the
      umbilical and middle cerebral artery offers at the moment.

PMID- 11242874
TI  - [Prognosis and treatment of chronic inflammatory bowel disease].
AB  - BACKGROUND, MATERIAL AND METHODS: Most studies of the prognosis of inflammatory
      bowel disease have not been population-based; they are retrospective reviews.
      Moreover, they lack uniform methods for assessment of outcome. The clinical
      course is difficult to predict and the prognosis has changed over the last
      decades as a result of progress in medical therapeutics and treatment principles
      and surgical methods. RESULTS: Patients suffering from Crohn's disease or
      ulcerative colitis will probably alternate between remission and relapse, with
      10% having a relapse-free course after ten years, and only 1% having a
      continuously active course. There is a cumulative frequency of operation of 50
      80% and of reoperation of 1/3 in Crohn's disease. In ulcerative colitis the
      overall probability of surgery is 1/3 for pancolitis and 10% for proctitis within
      five years of diagnosis, and the majority of patients are operated on within the
      first few years. Maintenance treatment with sulphasalazine (SASP) and 5
      aminosalicylic acid (5-ASA) in ulcerative colitis has reduced relapse rates to
      about the half. INTERPRETATION: Changes in disease distribution in ulcerative
      colitis are part of the natural course of the disease. This should have
      implications for medical treatment strategies. Inflammatory bowel disease
      frequently requires potent medication with side-effects that limit patients'
      acceptance. Certain environmental factors as well as patient compliance are
      thought to determine the clinical outcome in ulcerative colitis and Crohn's
      disease.

PMID- 11242875
TI  - [Pregnancy and labor in ulcerative colitis and Crohn disease].
AB  - BACKGROUND: About one quarter of women with the diagnosis conceive after the
      diagnosis has been made, and patients and clinicians are concerned about the
      health of the foetus and the possible side effects of medical and surgical
      treatment. MATERIAL, METHODS AND RESULTS: A survey of the literature shows that
      the general outlook is positive. The lifetime risk of developing inflammatory
      bowel disease if one of the parents has ulcerative colitis or Crohn's disease is
      5-10 per cent. The fertility seems to be more or less normal for ulcerative
      colitis and slightly lower for Crohn's. Women with active disease at the time of
      conception have a higher risk of early miscarriage, fetal death and still birth.
      It is therefore advisable that the disease is in a stable and inactive phase at
      the time of conception. The rule of thumb is that one in three gets worse and one
      in three improves during pregnancy. The indications for surgery are the same as
      for non-pregnant patients. Relapses during pregnancy should be treated in the
      same way as in non-pregnant patients. Apart from methotrexate, most drugs used
      regularly to treat ulcerative colitis and Crohn's disease can safely be used by
      pregnant women. The same guidelines as for non-pregnant patients apply in terms
      of indications and dosage. INTERPRETATION: In general there is no need to advise
      these patients against conceiving.

PMID- 11242876
TI  - [Finding the cause of death in intrauterine death--which examination should be
      done?].
AB  - BACKGROUND: The incidence of antepartum fetal death after 22 weeks of gestation
      is about 0.4% in Oslo, Norway. Screening routines will decide how many cases will
      remain unexplained. One quarter are diagnosed as Sudden Intrauterine Unexplained
      Death (SIUD). Precise knowledge of the cause of death is needed as a basis for
      counselling, prevention and treatment. MATERIAL AND METHODS: The implementation
      of diagnostic routines in stillbirths in Oslo from 1986 to 1995 was examined. A
      structured review has been prepared and new guidelines for diagnostic procedures
      have been adopted by The Perinatal Committees of Oslo and Akershus. RESULTS:
      Autopsies and placental investigations were performed in 88% of intrauterine
      deaths. Among SIUD cases (all autopsied), infectious causes were examined and
      excluded in 93%. In contrast Kleihauer-Betke test was performed in only 17%,
      autoantibodies explored in 24%, and glucose tolerance tested in 36% of cases. The
      recommended laboratory investigations are: autopsy, placental investigation,
      bacteriological culture and investigations of infections such as Toxoplasma
      gondii, cytomegalovirus, parvovirus B19 and Listeria monocytogenes, Kleihauer
      Betke test, screening for diabetes, chromosome analysis of amniotic fluid and
      placental biopsy, and serology of antiphospholipids. INTERPRETATION: Both the
      content and implementation of diagnostic routines in the cases of antepartum
      fetal death has not been optimal in our region; there is need for a change.

PMID- 11242877
TI  - [Sleep habits among adolescents].
AB  - BACKGROUND: Norwegian adolescents report very high-perceived morning sleepiness.
      Delayed sleep phase may be biologically linked to puberty; adolescents sleep
      less, but may need more sleep than prepubertal children. The study was designed
      to investigate sleep habits, circadian rhythm and subjective satisfaction with
      sleep. MATERIAL AND METHODS: Twenty-two high school students, age 17, and parents
      of 16 primary school pupils, age seven, answered a questionnaire on estimated
      sleep need, actual time in bed, sleep latency and adequacy of sleep. RESULTS: The
      average length of nocturnal sleep in the adolescents was 7.3 hrs on weekdays and
      10.1 hrs on weekends. They went later to bed and rose earlier than the children,
      sleeping 1.7 hrs less before schooldays and 1.6 hrs more during the weekend than
      the 8.5 hrs which were their own sleep estimate. All the children were reported
      to satisfy their need for sleep, but none of the adolescents reported feeling
      content. The larger the difference between hours in bed on weekdays and hours in
      bed on weekends, the more dissatisfaction was observed. INTERPRETATION: The
      present data suggest that the adolescents were chronic partially sleep deprived
      and had a tendency toward delayed sleep phase. They did not satisfy their need
      for sleep as defined by themselves, due to late bedtime throughout the week.
      Also, the late bedtime and late rise time on weekends maintained or furthered the
      delayed sleep phase.

PMID- 11242878
TI  - [Refsum disease--rare, but world-famous].
AB  - Sigvald Bernhard Refsum (1907-91) was an outstanding Norwegian neurologist,
      highly respected and recognised both nationally and internationally. His main
      scientific achievement was that he by clinical means singled out a previously
      unknown disease entity in the multitude of different neurodegenerative features.
      In his monograph from 1946 he named the disease "heredopathia atactica
      polyneuritiformis"; however, it was rapidly known as Refsum's disease. Twenty
      years later, two German scientists, Klenk and Kahlke, detected large amounts of a
      peculiar branched-chain fatty acid, phytanic acid, in a Refsum patient. This
      started an amazing revelation of the biochemical background of the disease, and
      also led to a logical and effective treatment. Although Refsum's disease is
      extremely rare, it has become well-known due to this elucidation of both the
      normal metabolism of phytanic acid and the pathophysiology of the disease.

PMID- 11242879
TI  - [What does characterize a good drug clinical trial?].

PMID- 11242880
TI  - [Gene therapy--status and recommendations in Norwegian health care system].
AB  - BACKGROUND: This article presents the main conclusions and the recommendations of
      a multidisciplinary group of experts appointed by the Norwegian Centre for Health
      Technology Assessment to assess the potential of gene therapy in clinical
      medicine. MATERIALS AND METHODS: Clinical gene therapy protocols, ongoing or
      completed with published results, if any, were identified through a systematic
      survey of descriptive protocols and publications. RESULTS: So far 3,000-4,000
      patients have been treated with gene therapy strategies in more than 400 clinical
      trials. In Norway the six first patients have been treated with gene therapy at
      The Norwegian Radium Hospital as part of two approved protocols for treatment of
      cancer. Gene therapy today is dominated by preclinical and clinical research.
      Most of the gene therapy protocols identified are in early phases (phases I and
      II) with few patients in each study; only three of the protocols represent phase
      III studies. Apart from the use of soluble antisense oligonucleotides against
      cytomegalovirus, gene therapy is not an established treatment modality today. In
      early clinical studies, however, promising results have been seen in treatment of
      cancer, in certain forms of cardiovascular diseases and also in a subgroup of
      inherited severe combined immunodeficiency. INTERPRETATION: The expert group
      recommends that it is now important to build up national competence in the field
      in two ways: 1) by building up infrastructure in selected milieus; 2) by starting
      a national programme for gene therapy research including both preclinical and
      clinical research. The article also considers ethical and legislative aspects and
      emphasises that gene therapy should continue to be carefully monitored for side
      effects.

PMID- 11242881
TI  - [Gene therapy for monogenic inherited diseases].
AB  - BACKGROUND: Monogenic inherited disorders are caused by a mutation in one single
      gene. Each of these disorders is very rare, but as there are many thousand
      different monogenic disorders, they represent a significant health problem. Most
      monogenic disorders are severe and have no cure. Gene therapy will therefore
      often be the only possible treatment. MATERIAL AND METHODS: Characterisation of
      the gene is necessary for the development of gene therapy, and at the present
      time only a limited number of the genes in relation to the total number of the
      severe monogenic disorders is known. RESULTS: Clinical trials for some of the
      monogenic disorders, such as cystic fibrosis, have been going on for many years.
      INTERPRETATION: In spite of the tremendous effort, it is so far not documented
      that patients have been cured of a monogenic disorder by gene therapy.

PMID- 11242882
TI  - [Gene therapy in primary immunologic failure].
AB  - BACKGROUND: Primary immunodeficiency diseases (PID) represent a group of rare,
      usually congenital diseases. In most cases they are caused by mutations in genes
      essential for normal function of the immune system, leading to severe deficiency
      in antimicrobial defences, in many cases associated with other clinical
      manifestations. During the last decade the genetic defect and the function of the
      normal gene in the immune system has been delineated for a number of PID. The
      diseases are usually serious, and curative therapy is not available unless
      allogeneic bone marrow transplantation is possible. PID is therefore considered
      an attractive goal for gene therapy. MATERIAL AND METHODS: A systematic survey
      was made of protocols for gene therapy available in major databases, as well as
      of published reports on trials with gene therapy in man. RESULTS: Clinical trials
      with gene therapy are ongoing in several types of PID. While no case of PID has
      been documented to be definitely cured with gene therapy up to now, a landmark
      finding was recently made, reporting the use of gene therapy to successfully
      treat two infants with a type of severe combined immunodeficiency (SCID).
      INTERPRETATION: Gene therapy holds considerable promise for treatment of several
      types of PID in the future. Important obstacles, which must be overcome, are
      partly associated with general problems in human gene therapy, partly with
      special difficulties associated with the complexity of the human immune system.

PMID- 11242883
TI  - ["Blood type diet"--science or fantasy?].

PMID- 11242884
TI  - [Erection to the bitter end?].

PMID- 11242885
TI  - [Adults with celiac disease can eat pure oat].

PMID- 11242886
TI  - [Senior politics].

PMID- 11242887
TI  - [Chiropractors and the right to sick-list patients].

PMID- 11242888
TI  - [Diagnosis and therapy in acute stroke: a rehabilitation center viewpoint].
AB  - The extent of the diagnostic work-up of patients with acute stroke was evaluated
      in 101 patients admitted for rehabilitation during a 4-month period in 1997. This
      included specific blood tests and neuro- and cardiac imaging, and compared the
      extent of work-up in a community hospital versus a rehabilitation center.
      Comparisons were also made with similar investigations 10 and 20 years earlier.
      Results demonstrated that the trend to admit younger stroke patients (< 50 years)
      to neurological (as opposed to medical) departments observed between 1977-1987
      persisted in 1997. The use of CT scan increased dramatically from 1977 to 1987
      (19% vs 78%), and in 1997 was actually 100%. The use of carotid duplex and
      echocardiography increased steadily during the 3 decades reaching 26% and 28%
      respectively. Tests for thrombophilia were seldom done. However, in neurological
      departments it was done in about 50% of the younger stroke patients. In neurology
      departments carotid duplex was done 2 to 3 times more often than in medical
      departments. During rehabilitation imaging tests were done once or more in almost
      half the patients. The results and those of additional blood tests, have led to
      modification of antithrombotic treatment in 14% of the younger group and 4% of
      the older group. We have clearly shown that while stroke work-up has become more
      comprehensive in recent years, there is still much to do in this field. Stroke
      units or teams in our general hospitals will increase stroke awareness, improve
      work-up and hasten definitive treatment.

PMID- 11242889
TI  - [Cholesterol pericarditis associated with rheumatoid arthritis].
AB  - Cholesterol pericarditis (CP) is a rare and unusual disease characterized by
      chronic pericardial effusion with high cholesterol concentration. Precipitation
      of cholesterol crystals may occur and induce inflammation and constrictive
      pericarditis. CP may be idiopathic, but is usually associated with a systemic
      disease, such as tuberculosis, myxedema, or as in our case, rheumatoid arthritis
      (RA). We present a 78-year-old woman with RA, typical deformities of the
      metacarpo- and metatarso-phalangeal joints and subcutaneous rheumatoid nodules.
      She was hospitalized with increasing dyspnea and weakness and a 2-dimensional
      transthoracic echocardiogram showed a large pericardial effusion, without
      tamponade. Blood cholesterol was 208 mg/dl, triglycerides 169 mg/dl, LDH 37 u/L
      and rheumatoid factor 2560 u; glucose, kidney, and thyroid function tests were
      normal and PPD test negative. Pericardiocentesis yielded 800 ml of opaque, cloudy
      fluid, with glucose 19 mg/dl, cholesterol 264 mg/dl (normal 20-40 mg/dl),
      triglycerides 169 mg/dl, LDH 5820 u/L and rheumatoid factor 40 u; viral titers
      and cultures for bacterial, mycobacterial and fungal infections were negative.
      The pericardial fluid had a distinctive scintillating, gold-paint appearance and
      many cholesterol crystals were evident microscopically. The patient responded to
      treatment with methotrexate and steroids. Factors responsible for increase in
      pericardial fluid cholesterol may be its liberation from injured pericardial
      cells and rheumatoid nodules, lysis of red cells, or lymphatic obstruction and
      impairment of the absorptive capacity of the pericardium.

PMID- 11242890
TI  - [Antioxidant profile of human saliva and its biological significance].
AB  - Saliva is the first biological medium to come in contact with materials entering
      the body through the oral cavity. These materials are contained in food and drink
      (or inhaled as volatile ingredients). Accordingly, saliva contains various
      defense mechanisms which have been thoroughly investigated. They include
      immunological and enzymatic systems aimed at pathological microorganisms. Saliva
      also can protect the mucosa against mechanical insults and when required, promote
      its healing via agents such as the epidermal growth factor. Another defense
      mechanism in saliva which has been gaining increased attention and seems to be of
      paramount importance is its antioxidant system. We discuss both the molecular and
      enzymatic components of the salivary antioxidant system in respect to mixed,
      parotid, submandibular and sublingual saliva and under various physiological
      conditions of secretion.

PMID- 11242891
TI  - [Surgical repair of myxomatous mitral valve].
AB  - Myxomatous mitral valve disease is now the most common cause of mitral
      regurgitation in the western world. Repair of the leaking valve has become
      standard surgical procedure during the past 2 decades. Between 1993-1999 we
      performed 113 repairs of the mitral valve. In 25 patients the etiology was
      myxomatous degeneration (no mortality). Long-term clinical results depend on
      patients' functional class at surgery. Based on this fact, and the good surgical
      results, it is recommended to refer such patients even with severe mitral
      incompetence for surgery at an early stage, even if symptoms are minimal.

PMID- 11242892
TI  - [Prevention and treatment of procedural pain in pediatric wards: collected
      guidelines].
AB  - Present knowledge and available pharmacological agents allow for adequate
      prevention and treatment of pain in children. We present guidelines we prepared
      for the prevention and treatment of procedural pain in children in our general
      pediatric ward. This followed extensive review of the literature, participation
      in scientific meetings, discussions with experts and consultation with interested
      clinicians. Successful implementation of the guidelines requires increased
      appreciation of the importance of pain prevention, participation of the nursing,
      as well as medical staff, and ability to evaluate pain in children of various
      ages.

PMID- 11242893
TI  - [Photodynamic therapy of nasal basal cell carcinoma].
AB  - Photodynamic therapy (PDT) is a noninvasive modality used topically for several
      skin cancers. We evaluated the effects of PDT on basal cell carcinoma (BCC) of
      the nose, using aminolevulinic acid (ALA) as a photosensitizer and a non-laser
      light source (Versa-Light). The advantages of this light source are synergistic,
      hyperthermia and fewer side effects. A paste of 20% ALA was applied topically to
      biopsy-proven BCC of the nose. Lesions were covered with occlusive light
      shielding dressing and after 18 hours they were submitted to 10 minutes of
      exposure to the light. Initial evaluation was made after 21 days and every 3
      months thereafter. Patients who did not respond after 2 treatments were referred
      for surgery. Mean follow-up in 31 patients was 19 months (range 6-36). There were
      no significant side-effects. There was complete response in 24/27 (88.9%), in
      whom there was recurrence in 2/27 (7.4%).

PMID- 11242894
TI  - [Retinal injury induced by laser pointers].
AB  - Laser pointers originally designed for use during presentations are ubiquitous
      and are even sold as toys (such as pens or on key chains) in drug stores. Though
      reported as safe, the laser pointers still carry the risk of potential damage to
      the eye. We report a 16-year-old boy with bilateral retinal injury caused by 20
      30 seconds of exposure to a laser pointing-device. Immediately thereafter, vision
      was blurred bilaterally and he noted a central red scotoma in each eye. Symptoms
      resolved spontaneously within 2 days but the retinal scars remained all during
      the 10 months of follow-up. It is clear from our report and 3 other publications
      that retinal damage can develop from misusing laser pointers. Laser hazards and
      safety should be stressed for the general public. We recommend that laser
      pointers should not be available as toys to children and teenagers.

PMID- 11242895
TI  - [Ethical challenges in the use of Internet].

PMID- 11242896
TI  - [Prevention of breast cancer--what are the latest developments?].

PMID- 11242897
TI  - [Update on new oral treatment for diabetes].

PMID- 11242898
TI  - [Screening for early detection of prostate cancer (first experience in Israel)].
AB  - Prostatic cancer (PC) is second only to lung cancer as a cause of cancer
      mortality in men word-wide. In Israel it is the most common cause of cancer
      mortality in men, after lung cancer and colo-rectal cancer. We screened, for the
      first time in Israel, for prostatic cancer using serum levels of PSA and a
      digital rectal examination (DRE). The purpose was not only to diagnose PC but
      also to increase public awareness of the condition. 300 men in the Haifa area who
      met statistical criteria for early diagnosis of PC participated. They filled a
      questionnaire regarding risk factors for PC (age, family history (FH) of
      prostatic and breast cancer, cigarette smoking, alcohol consumption, previous PSA
      sampling) and were examined. Those who had out-of-range, age-related PSA values,
      or a pathologic DRE underwent trans-rectal ultrasound (TRUS) examination and
      guided biopsy of the prostate. Those with a positive biopsy for PC underwent
      radical prostatectomy or radiation therapy. 41 (14.3%) had out-of-range, age
      related PSA levels and 10 (3.5%) had a pathologic DRE. 39 (13.3%) underwent TRUS
      and biopsy and 6 (2.04%) had clinically significant PC, all early stages (Gleason
      4-6). Correlation between age and PSA has been proven statistically significant
      (p < 0.05). Symptoms of urinary tract obstruction and nocturia were related to a
      high PSA (p = 0.035 and 0.002, respectively). Those with PC had at least 1
      symptom of urinary tract obstruction; 6 (15.3%) who underwent TRUS and biopsy and
      a FH of prostate cancer. However, no subject with a FH of PC had biopsy-proven
      cancer. Those with PC had PSA values from 4.9 to 31.8 ng/ml (9.6 median). Age
      related PSA had a positive predictive value of 17.1%. Results of our annual
      screening for early detection of PC using age-related PSA, and DRE are
      encouraging: cases detected were clinically significant and treatable. It would
      appear that screening for PC will result in decreasing the incidence of
      metastatic cancer and therefore mortality.

PMID- 11242899
TI  - [Central nervous system involvement in antiphospholipid syndrome].

PMID- 11242900
TI  - [An approach to insomnia in the elderly].

PMID- 11242901
TI  - [The syndrome of cardiac arrest induced by a chest blow--another reason for
      sudden death in athletes; a known accident causing sudden cardiac death in
      sports].

PMID- 11242902
TI  - [Silicone as a therapeutic aid in the treatment of hypertrophic scars and
      keloids].

PMID- 11242903
TI  - [Pathologies leading to anovulation and the impact on women's health].

PMID- 11242904
TI  - [Mechanism of action of antiepileptic drugs in bipolar affective disorder].

PMID- 11242905
TI  - [Complications of blood transfusion in neonates and prematures].

PMID- 11242906
TI  - [Sexual health promotion--an inductive intervention model].

PMID- 11242907
TI  - [Bibliokleptomania].

PMID- 11242908
TI  - [Paul Gyorgy (1893-1976)].

PMID- 11242909
TI  - [Contribution of PET using FDG in the diagnosis of lung cancer--first results].
AB  - Positron emission tomography (PET), when used with F-18 fluoro-deoxyglucose
      (FDG), contributes to the evaluation of patients with lung cancer. This technique
      of imaging detects active tumor tissue by showing increased radiopharmaceutical
      uptake by metabolically active cells. Thus, PET assists in the early diagnosis of
      pulmonary malignancies that appear only as non-specific findings on CT-scan or
      chest X-ray. In addition, it is helpful in staging lung cancer before and after
      resection, chemotherapy or radiotherapy, or their combined use. We performed 135
      FDG-PET studies between July '97-April '99 and present our preliminary results
      with examples of the main indications for PET in lung cancer.

PMID- 11242910
TI  - [Diagnostic laparoscopy--a useful tool in abdominal lymphoma].
AB  - Imaging-guided (CT/US) percutaneous biopsy has significantly improved diagnosis
      of intra-abdominal lymphoma. However, in many cases the tissue retrieved may be
      inadequate for specialized studies such as immunophenotyping or cytogenetic
      analysis that may be required for a complete analysis of lymphoma or
      determination of therapy. The success of diagnostic laparoscopy in the diagnosis
      and staging of gastrointestinal malignancies suggests that it could be used for
      intra-abdominal lymphomas as well. We describe our experience in 15 patients with
      suspected lymphoma who underwent diagnostic laparoscopy during 1995-98.
      Preoperative investigation performed in all included percutaneous FNA in 9
      without conclusive diagnosis. Laparoscopy was diagnostic for lymphoma in 14 (93%)
      while in 1 there was a false negative result due to sampling error and the
      lymphoma was only diagnosed at a second laparoscopy. There was no mortality nor
      any major complication. Average hospital stay was 2 days and patients were then
      referred for further oncological treatment. Our experience shows that diagnostic
      laparoscopy is a safe and efficient tool and without major complications in
      diagnosing abdominal lymphoma.

PMID- 11242911
TI  - [Metallic stents for acute colonic obstruction].
AB  - The traditional treatment of acute colonic obstruction, usually caused by
      malignant tumor, is a 2-stage surgical procedure. The first operation is emergent
      and includes primary tumor resection and end colostomy followed by scheduled
      colostomy closure. These operations are associated with high mortality and
      morbidity. Recently, insertion of self-expanding metallic stents for temporary
      colonic decompression has been was introduced. With this new technique colostomy
      can be avoided in the acute phase. In advanced colonic cancer stent-insertion is
      the only palliative treatment. It is done in the radiology department under
      fluoroscopic guidance. We present 2 cases of malignant colonic obstruction
      treated successfully by stent insertion.

PMID- 11242912
TI  - [Heart rate variability in the elderly with syncope or falls of uncertain
      origin].
AB  - Presyncope, syncope and falls in undetermined circumstances are frequent among
      the elderly. They may be caused by orthostatic hypotension secondary to autonomic
      insufficiency. Tilt-tests and determination of catecholamines in serum and urine
      may establish the diagnosis, but often may not be feasible in these patients. A
      simple, indirect, noninvasive technique to assess autonomic insufficiency is
      analysis of heart rate variability during Holter-monitoring. We present 5 cases
      in which it proved useful in the investigation of spells of unconsciousness.

PMID- 11242913
TI  - [Tuberculous meningitis in AIDS--diagnosis and treatment].
AB  - The increase in prevalence of tuberculous meningitis during the past decade has
      been attributed in part to the increase of AIDS. Failure to diagnose HIV can
      cause irreversible damage and even death. We describe a man with AIDS admitted
      through the emergency room because of high fever and headaches for more than a
      month, He was cachectic and had nuchal rigidity without major neurological
      deficit. Brain imaging was normal and lumbar puncture showed neutrophils,
      lymphocytes, hypochloremia, elevated protein, and decreased glucose; cryptococcal
      antigen was negative but acid-fast staining was positive. Anti-TB chemotherapy
      was started using 4 drugs and dexamethasone was also given. Considerable
      improvement in his general condition followed rapidly. Use of corticosteroids in
      tuberculous meningitis has been a major issue. They are added to antimicrobial
      agents in order to decrease reactivity of inflammatory mediators and thus reduce
      central nervous system damage. We review several controlled studies in which
      steroids were added to treat tuberculous meningitis. The conclusions of most were
      that they decrease morbidity and mortality, especially of those moderately to
      severely ill. Most considered as ungrounded the possibility of exacerbating
      latent tuberculous, or any other opportunistic infection outside the central
      nervous system. However, it is currently recommended to add prednisone, 1 mg/kg/d
      for 2-4 weeks when initiating anti-tuberculous treatment.

PMID- 11242914
TI  - [Aggressive surgical approach in pancreatic cancer--is it justified?].
AB  - Resection presents the only possible cure for pancreatic cancer. An aggressive
      surgical approach may extend the limits of resection and offer cure for more
      patients. 37 women and 28 men, mean age 67 years (range 33-84) with focal lesions
      underwent pancreatic resection (1993-1999). Cancer of the pancreatic head was
      found in 45, in the ampulla in 4 and in the body or tail in 16. There was a tumor
      larger than 5 cm in 9, vascular involvement in 8, and a combination of both in 6.
      All were evaluated prior to exploration by standard imaging techniques and 44 by
      laparoscopic ultrasound. 42 underwent pancreatico-duodenectomy, 16 distal
      subtotal pancreatectomy and 3 local excision of an ampullary tumor. Benign
      lesions were found in 8 (focal pancreatitis in 4 and a serous cystic lesion in
      4). Curative resection (microscopically negative margins, negative lymph nodes)
      was achieved in 44. 2 died 1-2 months after operation of septic complications (2%
      operative mortality). The most frequent complication (in 8) was pancreatic
      fistula. Additional complications included anastomotic-line bleeding (3), intra
      abdominal abscess (2), and 1 developed portal vein thrombosis (treated
      surgically). 1- and 2-year survival in those after curative pancreatic resection
      was 81% and 55% respectively. 2-year survival in those after palliative resection
      (positive resection margins or positive lymph nodes) was 50% and 11%,
      respectively. After proper selection of those in whom it is possible to perform
      curative resection, regardless of size or vascular involvement, an aggressive
      surgical approach is justified.

PMID- 11242915
TI  - [In vitro interferon-gamma release--a laboratory diagnosis of cutaneous adverse
      drug reactions].
AB  - Diagnosis of cutaneous adverse drug reactions is an accepted terminology. Is a
      challenge. Drug-specific T-cell clones (CD4+ or CD8+), with a Th1- or a Th2-type
      cytokine-release pattern, may be generated from the peripheral blood in CADRs. In
      vitro drug-induced cytokine-release suggests a drug-specific immune response, and
      may implicate the drug as a possible inducer of the skin reaction. We evaluated
      the diagnostic role of in vitro drug-induced interferon-gamma (IFN-gamma) release
      from peripheral blood lymphocytes in patients with CADRs. We studied 22 patients
      with CADRs following intake of 45 drugs (1-4 drugs per patient). Drugs were
      classified into 3 categories of suspicion. 17 patients who took 39 drugs of the
      same type (1-4 drugs per patient) without developing adverse reactions, served as
      controls. In vitro drug-induced release of IFN-a from peripheral blood
      lymphocytes, following in vitro challenge with the unmodified drugs, was
      evaluated. The mean IFN-gamma increase following 45 drug tests (60.8 +/- 85.2%)
      was higher (p < 0.05) than in controls after 39 drug tests (30.1 +/- 27.7%).
      Significance was greater (p < 0.005) when the mean IFN-gamma increase for the 24
      highly suspected drugs (75.1 +/- 93.4%) and that for the controls were compared.
      This study suggests that the in vitro drug-induced IFN-gamma release test may
      serve as a diagnostic tool in CADRs.

PMID- 11242916
TI  - [The Nobel Prize for Medicine 2000].

PMID- 11242917
TI  - [Association between periodontitis, gingivitis and atherosclerosis; are they
      connected?].

PMID- 11242918
TI  - [Cesarean section upon maternal request].

PMID- 11242919
TI  - [The significance of matrix metalloproteinases in vascular biology].

PMID- 11242920
TI  - [Alzheimer disease and estrogen--the connection, modes of influence and the
      therapy].

PMID- 11242921
TI  - [Cutaneous malignant melanoma of head and neck--an update].

PMID- 11242922
TI  - [Cryosurgery in prostate cancer].

PMID- 11242923
TI  - [Uterine artery embolisation for symptomatic leiomyomata uteri--a new treatment
      method].

PMID- 11242924
TI  - [Low education and high education in Alzheimer's disease--what is worse?].

PMID- 11242925
TI  - [Bronchiolitis obliterans and bronchiolitis obliterans with organizing pneumonia:
      the different and the common].

PMID- 11242926
TI  - [Active management of labor and cesarean section rate].

PMID- 11242927
TI  - [The diagnosis of pulmonary embolism with spiral computer tomography].

PMID- 11242928
TI  - [Should age be considered in the treatment of the old patient with acute coronary
      syndrome].

PMID- 11242929
TI  - [The contribution of Jewish physicians in Denmark to the advancement of
      medicine].

PMID- 11242930
TI  - [Dr. Virginia Apgar--1909-1974].

PMID- 11242931
TI  - [From military medicine to militant literature: George Duhamel].

PMID- 11242932
TI  - [The active role of the passive verb in medical articles].

PMID- 11242933
TI  - [Dr. Sidney Farber (1903-1973)].

PMID- 11242934
TI  - [Intraventricular hemorrhage in full-term neonates].
AB  - Intraventricular hemorrhage in full-term neonates is rare; it may develop without
      any clinical signs. Its cause is not fully understood although some risk factors
      have been identified. A higher index of suspicion would ensure earlier diagnosis
      and treatment, which might reduce the rate of severe complications. We describe 2
      cases in full-term neonates.

PMID- 11242935
TI  - [Video-assisted thoracic surgery--experience with 586 patients].
AB  - Recent advances in optics, video systems and endoscopic operating instruments
      have led to increasing application of thoracoscopic surgery, as it has become
      easier to perform and more accurate. We performed 586 video-assisted thoracic
      surgical procedures for diagnosis and treatment (May 1992-Dec. 1998) 127 were for
      diagnostic thoracoscopy and 79 for pleurodesis. 380 cases of operative
      thoracoscopy included pulmonary wedge resection (for interstitial lung disease,
      benign and malignant pulmonary tumors and pulmonary metastases) bullectomy,
      management of empyema, pleural tumor biopsy, thoracic sympathectomy, pericardial
      window formation, thoracic spinal procedures and resection of posterior
      mediastinal cysts. Recently we have had good experience in evacuating blood and
      blood clots from the thorax which accumulated after cardiac and thoracic surgery.
      Patients were placed in the lateral thoracotomy position and were ventilated with
      a double-lumen endotracheal tube, enabling collapse of the operated lung. The
      operating approach was through 1-3 thoracic ports. Mean operation time was 55
      minutes, chest-tubes remained for 2.2 days (mean) and mean hospitalization was
      3.3 days. There were no wound infections or significant postoperative
      complications. 5 patients had air leaks longer than 7 days; none required further
      surgical intervention. There was intercostal neuralgia and Horner's syndrome
      after thoracic sympathectomy (1 each) In cases in-which localizing the
      parenchymal lesion was difficult, the lung was palpated directly by inserting a
      finger through a small incision or a mini-thoracotomy. Conversion to thoracotomy
      was performed when primary malignancy of lung was diagnosed by frozen section.
      Only 2 patients had thoracotomy for uncontrolled bleeding. Thoracoscopy is a
      minimally invasive surgical technique with very low morbidity and high diagnostic
      accuracy. Postoperative recovery is brief and uneventful.

PMID- 11242936
TI  - [Long-term sequelae of malignant tumors in childhood: consequences of late side
      effects].
AB  - 110 children with malignant diseases (leukemia excepted) who survived 5-20 years
      (median 9) post-therapy were followed (1996-1998). Median age during follow-up
      was 15 years (range 5-23). The most common malignancies were brain tumors,
      lymphoma, retinoblastoma and Wilm's tumor. The 174 late side-effects included
      endocrine disorders (19%), cognitive impairment (14%), orthopedic dysfunction
      (12%), alopecia (12%), dental damage (11%), psychological (8%) and neurological
      (8%) disturbances, and azoospermia or amenorrhea (5%). There was no cardiac or
      renal damage and no second malignancy. 29% of side-effects were severe. There was
      significant reduction in quality of life in 54 (49%), in 27 of whom it was severe
      enough to require psychological intervention. Treatment of brain tumor caused 98
      late side-effects in 28 patients (sequelae-to-patient ratio [SPR] 3.3). Most
      cognitive, endocrine and neurological disorders, and most cases of alopecia,
      dental and psychological difficulties were in these patients. There were frequent
      late complications in those treated for retinoblastoma (SPR 1.8), and bone or
      soft tissue sarcomas (SPR 0.8). Those treated for Wilm's tumor had few side
      effects (SPR 0.4). Late side effects were most frequent after radiation, reaching
      as high as SPR 2.4. It averaged only 0.5 in those treated with chemotherapy alone
      or in combination with surgery. Reduction of late side-effects in these patients
      requires using less toxic modalities, as long as cure rate is not compromised.
      When considering secondary strategies, screening for early detection of late
      complications would enable immediate solutions, such as hormonal replacement or
      providing compensating skills for post-treatment disability.

PMID- 11242937
TI  - SSCP analysis of point mutations by multicolor capillary electrophoresis.

PMID- 11242939
TI  - Magnetic bead-isolated single-strand DNA for SSCP analysis.

PMID- 11242938
TI  - SSCP analysis by capillary electrophoresis with laser-induced fluorescence
      detector.

PMID- 11242940
TI  - Analysis of short tandem repeat markers by capillary array electrophoresis.

PMID- 11242941
TI  - Genotyping by microdevice electrophoresis.

PMID- 11242942
TI  - Applications of constant denaturant capillary electrophoresis and complementary
      procedures. Measurement of point mutational spectra.

PMID- 11242943
TI  - Ultra-fast DNA separations using capillary electrophoresis.

PMID- 11242944
TI  - Toward effective PCR-based amplification of DNA on microfabricated chips.

PMID- 11242945
TI  - Low-stringency single specific primer-amplified DNA analysis by capillary
      electrophoresis.

PMID- 11242946
TI  - DOP-PCR amplification of whole genomic DNA and microchip-based capillary
      electrophoresis.

PMID- 11242948
TI  - Chemical mismatch cleavage analysis by capillary electrophoresis with laser
      induced fluorescence detection.

PMID- 11242947
TI  - Analysis of triplet-repeat DNA by capillary electrophoresis.

PMID- 11242949
TI  - Quantitation of mRNA by competitive PCR using capillary electrophoresis.

PMID- 11242950
TI  - Quantitative RT-PCR from fixed paraffin-embedded tissues by capillary
      electrophoresis.

PMID- 11242951
TI  - Differential display analysis by capillary electrophoresis.

PMID- 11242952
TI  - Capillary array electrophoresis analyzer.

PMID- 11242953
TI  - DNA sequencing at elevated temperature by capillary electrophoresis.

PMID- 11242954
TI  - Development of a high-throughput capillary electrophoresis protocol for DNA
      fragment analysis.

PMID- 11242955
TI  - DNA sequencing in noncovalently coated capillaries using low viscosity polymer
      solutions.

PMID- 11242957
TI  - Sequencing of RAPD fragments using 3'-extended oligonucleotide primers.

PMID- 11242956
TI  - Selective primer sequencing from a DNA mixture by capillary electrophoresis.

PMID- 11242958
TI  - Capillary affinity gel electrophoresis.

PMID- 11242959
TI  - Capillary DNA-protein mobility shift assay.

PMID- 11242960
TI  - Protein-DNA binding affinities by capillary electrophoresis.

PMID- 11242961
TI  - Ligand binding to oligonucleotides.

PMID- 11242963
TI  - Detection of DNA polymorphisms using PCR-RFLP and capillary electrophoresis.

PMID- 11242962
TI  - Fast DNA fragment sizing in a short capillary column.

PMID- 11242964
TI  - High resolution analysis of point mutations by constant denaturant capillary
      electrophoresis (CDCE).

PMID- 11242965
TI  - Point mutation detection by temperature-programmed capillary electrophoresis.

PMID- 11242966
TI  - Single-nucleotide primer extension assay by capillary electrophoresis laser
      induced fluorescence.

PMID- 11242967
TI  - Amplification refractory mutation system analysis of point mutations by capillary
      electrophoresis.

PMID- 11242968
TI  - Lessons about AIDS and the circle of life.

PMID- 11242969
TI  - The sounds of silence. AIDS in Zimbabwe.

PMID- 11242970
TI  - On the brink: despair and hope in Tanzania.

PMID- 11242971
TI  - AIDS in Africa. A global responsibility.
AB  - The global response to the AIDS epidemic has often been marked by ignorance,
      fear, shame, and complacency, resulting in a spiraling epidemic in Africa and
      elsewhere. However, when leaders have confronted the realities of HIV with candor
      and empathized with those stricken with AIDS, the results are encouraging.
      Because infectious diseases and their consequences do not respect political
      borders, HIV presents many challenges for both developing and industrialized
      nations. AIDS in Africa represents a global challenge and requires sustained
      political and monetary investments. In 1998, only $300 million in international
      assistance funds were available for combating HIV/AIDS. However, an estimated
      $1.6 billion to $2.6 billion annually may be needed to mount an effective
      response in sub-Saharan Africa alone. Those dollars equal less than $3.50 per
      person in this region, or less than a bottle of cold medicine one of us might
      purchase at a U.S. pharmacy. Failure to act aggressively now will cost the world
      economically and socially, and will result in the loss of millions of lives.

PMID- 11242973
TI  - MMA cultural competence seminar focuses on the Somali patient.

PMID- 11242972
TI  - Sierra Leone's children of war.

PMID- 11242974
TI  - Physician liability and complementary health care.

PMID- 11242975
TI  - The impact of the 1997 Balanced Budget Act on Medicare, Part II.

PMID- 11242976
TI  - Physician spouses making a difference.

PMID- 11242977
TI  - The tie that binds global health.

PMID- 11242978
TI  - [131I meta-iodobenzylguanidine in combination with hyperbaric oxygen therapy in
      the treatment of prognostically high-risk forms of neuroblastoma].
AB  - BACKGROUND: Despite of improving diagnostics, development of new drugs and
      treatment strategies, patients with biologically unfavourable, advanced or
      relapsed neuroblastoma remain practically incurable. Treatment related toxicity,
      requirement for personnel and financial costs have became limiting. Tumor
      specific therapy represented by 131I-meta-iodobenzylguanidine (MIBG)
      administration could become an alternative improving the overall survival. In
      comparison with standard external radiotherapy the targeted therapy enables to
      achieve radiation 5 to 10 times higher with lower organ toxicity. Data published
      by European and American colleagues brought evidence of high efficacy of this
      method. It motivated us to set and develop the method at our department. TYPE OF
      STUDY: Retrospective analysis of therapeutic results and side effects of the
      administration of 131I-meta-iodobenzylguanidine in high-risk neuroblastoma
      patients cured at the Department of Pediatric Oncology in Prague since 1997 till
      2000. METHOD AND RESULTS: 131I-meta-iodobenzylguanidine was fourteen times
      therapeutically administered in seven high-risk relapsed neuroblastoma patients.
      Four children received a single dose of 131I-meta-iodobenzylguanidine, three
      patients were treated repeatedly. The first dose represented 5.5 GBq, repeated
      dose 3.7 GBq, irrespective to the body weight. Each MIBG administration was
      followed by four days hyperbaric oxygen therapy. The treatment was well
      tolerated, acute and late side effects were not serious and only rarely reached
      grade 3 or 4 according to the International North American Children's Cancer
      Group Classification. Three of the seven children have survived with no evidence
      of the disease. Four children died of the disease progress. CONCLUSIONS: 131I
      meta-iodobenzylguanidine treatment combined with hyperbaric oxygen therapy
      becomes a well-tolerated therapy for high-risk neuroblastoma patients non
      responding to the conventional treatment. Though the 131I-meta
      iodobenzylguanidine administration probably cannot cure these patients, the
      repeated administration can bring long lasting remission.

PMID- 11242979
TI  - [Screening for mutations in apolipoprotein B genes in a group of patients with
      hyperlipoproteinemia].
AB  - BACKGROUND: Familial defective apolipoprotein (apo) B-100 (FDB) is a common
      inherited metabolic disorder. Reduced binding of the apo B-100, the major protein
      of LDL particles, to LDL receptor results in marked hypercholesterolemia. FDB is
      caused particularly by an arginine to glutamine substitution at the codon for
      amino acid 3500 of the apo B-100. The aim of this study was to determine
      mutations potentially responsible for hypercholesterolemia in the apo B gene and
      to estimate their frequency in the group of Czech hyperlipidemic patients.
      METHODS AND RESULTS: The groups of 169 unrelated patients with primary isolated
      hypercholesterolemia (total cholesterol > or = 6.5 mmol/l, triglycerides < or =
      2.3 mmol/l) and 58 unrelated patients with combined hyperlipoproteinemia (total
      cholesterol > or = 6.5 mmol/l, triglycerides > 2.3 mmol/l) were screened for
      mutations in codon 3500 region of the apolipoprotein B gene by denaturing
      gradient gel electrophoresis. Mutation R3500Q was detected in 20 patients with
      isolated hypercholesterolemia (11.8%) and in 2 patients with combined
      hyperlipoproteinemia (3.4%). No other mutations were found. CONCLUSION: The
      frequency of FDB in our group of patients with primary isolated
      hypercholesterolemia is high when compared with data published in other
      countries. We suggest that all patients with primary isolated
      hypercholesterolemia (total cholesterol > or = 6.5 mmol/l) in the Czech Republic
      should be analysed for the presence of mutation R3500Q in the apo B gene.

PMID- 11242980
TI  - [Rapamycin: a new immunosuppressive agent capable of inhibiting chronic
      rejection?].
AB  - Chronic rejection represents the most common cause of transplanted graft loss in
      the long term. Rapamycin (sirolimus), and it's derivate RAD, are new and potent,
      immunosuppressive drugs. They inhibit cell proliferation driven by various growth
      factors. These drugs were successfully tested in some experimental models of the
      chronic rejection. Results of the first clinical trials have defined rapamycin
      pharmacokinetics and proved immunosuppressive efficacy. Rapamycin acts
      synergistically with cyclosporin A. The side effects are a dose-dependent
      thrombocytopenia and leukopenia but the most frequent is hyperlipidemia. The
      question, if rapamycin and RAD inhibit development of chronic rejection in man,
      will be solved by the prospective clinical trials over years.

PMID- 11242981
TI  - [The Coris, a married couple native to Prague and Nobel laureates].
AB  - The husband and wife Carl Ferdinand Cori (1896-1984) and Gerty Theresa Radnitz
      Cori (1896-1957), two of five Prague-born Nobel laureates (the only ones in
      medicine), have so much slipped away from the citizens' memory in the course of
      the half-century totalitarian rule over the country of birth, that hardly anybody
      knows them nowadays, nothing to say of their relation to Prague. At pains to
      rescue them from oblivion, a recent search for the lost traces of Coris and their
      ancestors had revealed a number of hitherto unknown facts that have fundamentally
      contributed to the Corian genealogy; identification of both forgotten birth
      houses (6 Salmovska st., 29 Petrska st.) at long last resulted in placement of
      memorial tablets (October 26th, 2000) to display the birth-place's pride and
      gratitude.

PMID- 11242982
TI  - [Social determinants of health. Basic facts and recommendations for practice
      within the context of the Health City Program].
AB  - Paper provides some basic information on selected social determinants of health
      that had been summarised in the process of creating, detailing, implementing and
      evaluating the European health policy led by WHO. The social areas discussed are:
      social gradient, stress, early life experiences, social exclusion, job control at
      work, unemployment, social support, addiction, food, and transport. We also
      present a brief summary of policy recommendations related to social determinants
      of health. This information is relevant both for the development of the health
      services system and the system of health care and policy in a broader sense.

PMID- 11242983
TI  - [Peroxisomes--characteristics, biogenesis and regulation of peroxisomal genes].
AB  - Peroxisomes represent cell organelles present in both unicellular eukaryotes and
      most of the animal and plant cells. Peroxisomes contain about 50 enzymes with
      high variability in spectrum and quantity, depending on nutritional conditions
      and presence of some xenobiotics (peroxisome proliferations). New peroxisomes are
      formed after the protein intake by splitting of the existing peroxisomes or de
      novo. Biogenesis of peroxisomes requires cytosolic proteins, membrane
      transporting proteins, and the typical groups of amino acids in polypeptide
      chains, which have the character of topogenic signal--PTS (peroxisomal targeting
      signal). PTS signal is based on the terminal tripeptide, formed usually by amino
      acids serine, lysine and leucine (SKL tripeptide--PTS1) or by the N-terminal PTS2
      with amino acid sequence Arg-Leu/Ile-XXXXX-Gln/His-Leu (X is any amino acid).
      Biogenesis of peroxisomes requires also special membrane proteins--peroxins,
      which are coded by PEX genes. These proteins act as homo- or heterodimes, they
      belong to ATP transports, and determine efficacy of the peroxisome biogenesis.
      Nuclear gene expression is regulated by nuclear receptors activated by peroxisome
      proliferators (PPAR-proxisome proliferators activated receptors). C-domain of the
      receptor binds to the specific region of the promotors of peroxisome genes (PPREs
      Peroxisomal proliferator response elements), often with tandem arrangement of
      sequences TGACCT. Polyunsaturated fatty acids represent the effective natural
      regulator of the peroxisomal gene expression.

PMID- 11242984
TI  - Null hypothesis significance testing. On the survival of a flawed method.
AB  - Null hypothesis significance testing (NHST) is the researcher's workhorse for
      making inductive inferences. This method has often been challenged, has
      occasionally been defended, and has persistently been used through most of the
      history of scientific psychology. This article reviews both the criticisms of
      NHST and the arguments brought to its defense. The review shows that the
      criticisms address the logical validity of inferences arising from NHST, whereas
      the defenses stress the pragmatic value of these inferences. The author suggests
      that both critics and apologists implicitly rely on Bayesian assumptions. When
      these assumptions are made explicit, the primary challenge for NHST--and any
      system of induction--can be confronted. The challenge is to find a solution to
      the question of replicability.

PMID- 11242985
TI  - The terrible twos--anger and anxiety. Hazardous to your health.
AB  - Anxiety and anger are hazardous to health. This article offers a selective review
      of research that illustrates how anxiety and anger increase vulnerability to
      illnesses, compromise the immune system, increase lipid levels, exacerbate pain,
      and increase the risk of death from cardiovascular disease and from all sources
      of death. Possible mechanisms for such effects are identified, including the role
      of cardiovascular reactivity. Finally, data are provided on Anxiety Management
      Training, a brief, structured psychological intervention that has proven
      effective in anxiety as well as anger management.

PMID- 11242986
TI  - Families and family psychology at the millennium. Intersecting crossroads.
AB  - This introduction to the International Perspectives section presents a global
      overview of various issues and trends that families and family psychologists
      confront at the beginning of the 21st century. These are presented in broad
      strokes so that a kaleidoscopic intermingling of pieces emerges. Some predictions
      are included about new and expanding directions the field of family psychology is
      likely to take in coming decades. The need for additional research to field test
      criteria sets for emerging relational diagnosis and to evaluate which are the
      most efficacious therapeutic interventions is highlighted (F. W. Kaslow, 1987,
      1995b). This section also includes 3 other articles on various aspects of family
      psychology by leading psychologists from 3 diverse countries and continents--the
      Virgin Islands (R. Dudley-Grant, 2001), Israel (E. Halpern, 2001), and Japan (K.
      Kameguchi, 2001). Each is representative of the larger region in which each
      author teaches and practices. These articles are intended to present a collage of
      some of the problems families are experiencing, future trends, and a call to
      action for psychologists to intervene to prevent and ameliorate family distress.
      Each author describes the history and current status of family psychology in his
      or her country and relates key dilemmas to what is happening on the world scene.

PMID- 11242987
TI  - Eastern Caribbean family psychology with conduct-disordered adolescents from the
      Virgin Islands.
AB  - Family psychology is a new and relatively undeveloped discipline in much of the
      English-speaking Caribbean, particularly in the U.S. Virgin Islands. Family
      structure and youth behavior in the region have changed dramatically over the
      past few decades. Given the family-oriented nature of the culture, it is posited
      that the use of family psychology as an approach to research and intervention may
      prove to be a rich method to address this cultural metamorphosis. This article
      examines the potential effectiveness of interventions at the family level when
      mental health providers are working with youth with conduct disorder in the
      Virgin Islands. This article is offered as a microcosm of the global changes in
      family structure and the youth culture that are occurring particularly in the
      developing world, in part due to the rapid development of telecommunications.
      Possible roles of the family psychologist in this global transformation are
      presented.

PMID- 11242988
TI  - Developmental science and the media. Early brain development.
AB  - Media coverage of early brain development not only has focused public attention
      on early childhood but also has contributed to misunderstanding of developmental
      neuroscience research. This article critically summarizes current research in
      developmental neuroscience that is pertinent to the central claims of media
      accounts of early brain development, including (a) scientific understanding of
      formative early experiences, (b) whether critical periods are typical for brain
      development, (c) brain development as a lifelong process, (d) biological hazards
      to early brain growth, and (e) strengths and limits of current technology in
      developmental brain research. Recommendations are offered for strengthening the
      constructive contributions of research scientists and their professional
      organizations to the accurate and timely coverage of scientific issues in the
      media.

PMID- 11242989
TI  - Family psychology from an Israeli perspective.
AB  - A perspective of family psychology in Israel is drawn against a background of
      evolving indigenous elaboration suited to Israel's unique circumstances (J. I.
      Good & A. Ben-David, 1995). Its development shows a progression from the original
      source of an enriching but dominant culture (J. J. Gergen, A. Gulerce, A. Lock, &
      G. Misra, 1996; E. Halpern, 1985) to a discipline growing within the Israeli
      geopolitical reality, constraints of academic infrastructures, and training
      resources. One can currently recognize a discipline that is increasingly
      congruent with its cultural texture as well as the histories and traditions of
      individual families in a multifaceted society. This evolution is thought to bear
      similarities to the course that family therapy originally took and to where the
      roots of family psychology can be found. To echo F. W. Kaslow's (1987, 1991)
      analysis of this evolution in the United States, the heritage of family
      psychology in Israel also basically lies in mainstream psychology.

PMID- 11242990
TI  - Family psychology and family therapy in Japan.
AB  - The development of family psychology and family therapy in Japan has occurred
      mostly since the 1980s. This development was originally activated by the major
      social issue in contemporary Japan of school refusal, in which more than 127,000
      children either overtly refuse to or claim that they cannot go to school. From a
      family perspective, this problem is analyzed as it relates to the confusion that
      children experience from unbalanced and unclear boundaries in family relations or
      "membranes." An approach to family therapy that adapts systems theory and
      integrates a clay sculpting medium has been developed to work with Japanese
      families confronting this problem. The design and implementation of preventative
      family psychology programs applied at the community level are also an important
      part of the future development in these fields.

PMID- 11242991
TI  - The downside of being talented.

PMID- 11242992
TI  - Choosing excellence.

PMID- 11242993
TI  - Well-being in cultures of choice: a cross-cultural perspective.

PMID- 11242994
TI  - A meaningful but modest positive psychology.

PMID- 11242995
TI  - God is a Libertarian?

PMID- 11242996
TI  - In defense of freedom.

PMID- 11242997
TI  - Freedom and tyranny: descriptions and prescriptions.

PMID- 11242998
TI  - Humanistic psychology and positive psychology.

PMID- 11242999
TI  - Is positive psychology only white psychology?

PMID- 11243000
TI  - Illogical positivism.

PMID- 11243001
TI  - Positive psychology: east and west.

PMID- 11243003
TI  - The values problem in subjective well-being.

PMID- 11243004
TI  - Rediscovering hope in American psychology.

PMID- 11243002
TI  - Prior positive psychologists proposed personality and spiritual growth.

PMID- 11243005
TI  - Positive psychology and positive reinforcement.

PMID- 11243006
TI  - Integrating psychopathology, positive psychology, and psychotherapy.

PMID- 11243007
TI  - The need for a principle-based positive psychology.

PMID- 11243008
TI  - [Increased fetal risk of primary venous thrombosis presenting at a young age].
AB  - Based on the hypothesis that the predisposition to thrombosis in women suffering
      from deep venous thrombosis at young age can disturb also the uteroplacental
      circulation, the authors retrospectively analyzed the fetal outcome of 333
      pregnancies in 101 women with thromboembolic event before 40 years of age and
      compared it to the fetal outcome of 2943 pregnancies in 1000 randomly selected
      obstetrical patients without thrombosis. The relative risks of adverse fetal
      outcomes in thromboembolic women were as follows: 1.85 (95% C.I.: 1.35-2.55) for
      the spontaneous miscarriage, 3.9 (95% C.I.: 2.20-6.93) for the second-trimester
      miscarriage, 1.74 (95% C.I.: 1.15-2.64) for the low birth weight, 2.82 (95% C.I.:
      1.28-6.30) for the perinatal loss and 7.17 (95% C.I.: 2.64-19.47) for the
      abruption of placentae. Data obtained suggest that women with deep venous
      thrombosis at young age should encounter a higher risk of the uteroplacental
      thrombosis which results in increasing fetal morbidity and mortality during the
      second and third trimesters of gestation.

PMID- 11243009
TI  - [Aquaporins in cerebral volume regulation and edema formation].
AB  - Regulation of tissue water content and brain volume is of critical importance for
      the normal functioning of the central nervous system (CNS), which, surrounded by
      the rigid cranium, is highly sensitive to any increase in the intracranial
      pressure. Alterations in cerebral water homeostasis and distribution may lead to
      neuronal and glial swelling known as cytotoxic brain edema, due to accumulation
      of intracellular water. Although numerous investigations have been performed to
      elucidate the underlying molecular basis and pathophysiology of brain edema,
      little is known about the regulation of water transport across the blood-brain
      barrier and between extra- and intracellular compartments of the brain
      parenchyma. The discovery and characterization of the aquaporin (AQP) family of
      membrane water channels provided molecular insight into fundamental processes of
      water transport across plasma membranes. Two AQPs are expressed abundantly in the
      mammalian brain: AQP1 in the apical plasma membranes of the cells of choroid
      plexus in the ventricles, where it has been suggested to participate in the
      secretion of cerebrospinal fluid and AQP4 in plasma membranes of ependymal cells
      and astrocytes. The role of AQP4 in the formation of brain oedema was suggested
      by some recent studies. These findings offer new potentials in brain oedema
      treatment.

PMID- 11243010
TI  - [Biomechanics in the pathogenesis of spondylosis and spondylolisthesis].
AB  - The etiology and predisposing factors of spondylolysis and spondylolisthesis,
      which are summarized in the first part of this article, have received
      considerable attention, but there biomechanics is little published. The goal of
      this article is to show a biomechanical model for the development of
      spondylolysis and spondylolisthesis. With mechanical equations it has been
      established, the pars interarticularis and the ligaments resist together the
      tensile and shear force, the bending moment if the pars interarticularis is
      uncracked. If the tensile stress in the pars interarticularis reaches its
      strength, crack occurs and the spondylolysis is developed. The cracked pars
      interarticularis is no longer capable of sustaining tension, the tensile force is
      transferred to the ligament. When the compressive strain of the pars
      interarticularis reaches its strain limit, the spondylolisthesis does not
      develop, because the vertebra can not slip with the unbroken ligaments. If the
      loading on the pars interarticularis would be decreasing, the cracks close and
      the pars interarticularis can ossify. If the tensile stress in the ligament
      reaches its strength and the ligament breaks, the pars interarticularis cracks
      through, the vertebra slips and the spondylolisthesis develops. In the last part
      of the article the methods of the conservative and operative treating are
      summarized.

PMID- 11243011
TI  - [Biatrial pacing--new possibility in the non-pharmacologic treatment of drug
      resistant paroxysmal atrial fibrillation].
AB  - Biatrial pacing seems to be a possible non-pharmacological therapeutic choice in
      the prevention of drug-refractory, paroxysmal atrial fibrillation. Biatrial
      pacing using standard right atrial and coronary sinus left atrial pacing shows an
      antiarrhythmic effect, which mechanism is not well understood. Biatrial pacemaker
      was implanted in three patients suffering from drug refractory, symptomatic
      paroxysmal atrial fibrillation (lone and nonvalvular in 2 and in one case,
      respectively). Interatrial conduction disturbance (P > 120 ms) was found in three
      case. Bradycardia dependent arrhythmia development was not observed. Left atrial
      and right atrial premature beats dominated in 2 and in one case, respectively. P
      wave duration was decreased by biatrial pacing in every patients. Atrial
      fibrillation has not been detected in two patients 1 day and 4 weeks after
      pacemaker implantation (follow up period: 9 and 5 months), however antiarrhythmic
      drugs has been withdrawn. In the number of left atrial premature beats a marked
      decrease was observed. Neither biatrial nor standard right atrial pacing nor
      combined medical and atrial pacing antiarrhythmic therapy were proven to be
      effective. In Hungary we were the first to implant and apply effectively biatrial
      pacemaker in the prevention of paroxysmal drug-refractory atrial fibrillation.
      However better identification the responding patients subgroup with atrial
      fibrillation is needed.

PMID- 11243012
TI  - [Urinary bladder and paraurethral endometriosis].
AB  - Authors report a case of bladder and a case of paraurethral endometriosis. The
      mode of sanitation was by means of TUR and surgery, respectively. Based on the
      available literary data, the assumptions related to development of the disease;
      its pathology, symptoms and treatment are discussed in brief. Despite the
      frequency of the disorder, exact diagnosis might take months, perhaps even years.
      Due to the difficulties in diagnosing this disease, correct diagnosis can be
      expected from biopsy, as in our case.

PMID- 11243013
TI  - [The pathological and clinical consequences of chronic cerebral hypoperfusion].
AB  - Comprehensive studies investigating clinical, biochemical and pathomorphological
      consequences of chronic cerebral hypoperfusion were carried out only in recent
      years. Despite of different pathological processes resulting in chronic
      reductions of cerebral blood flow, the pathophysiological, biochemical and
      pathomorphological alterations and the clinical consequences are causing or
      modifying the pathological and clinical pictures in a similar manner. Cerebral
      hypoperfusion is verifiable in patients with ischaemic strokes, in diseases
      characterised by mild or serious cognitive impairment and in dementias of
      vascular or of degenerative origins, even it can be shown in normal ageing. This
      review gives a summary of pathophysiological, pathomorphological and clinical
      consequences of chronic cerebral hypoperfusion, and the role of that in evolution
      and persistence of cognitive disturbances.

PMID- 11243014
TI  - [Hemodynamic effects of propofol induction administered with target controlled
      infusion pump in patients scheduled for open heart surgery].
AB  - Target controlled infusion systems have been developed to provide improved
      convenience and control during intravenous anaesthesia. The anaesthetist sets and
      adjust the target blood concentration and depth of anaesthesia--as required on
      clinical grounds. Infusion rates are altered automatically according to a
      validated pharmacokinetic model. Haemodynamic effects during induction of
      anaesthesia with target controlled infusion pump have been documented in this
      prospective study. Twenty patients scheduled for open heart surgery. Mean age
      62.2 +/- 9.93 years. The surgical procedures were: 16 coronary bypass, 2
      artificial valve replacement, 2 coronary bypass combined valve replacement.
      Anaesthesia was induced with alfentanil, 20-40 micrograms/kg, and propofol
      administered with target control infusion pump, 1.5-4 micrograms/ml target
      concentration. Pulse contour analysis was used for haemodynamic measurements.
      They were repeated before induction (T0), after induction--before intubation
      (T1), after intubation in two minutes intervals (T2-T5). Compared with values
      obtained in awake patients, there was a significant decrease in mean arterial
      pressure (-30%), in cardiac output (-25%), in heart rate (-8%), in vascular
      resistance (-9%), in contractility (-37.4%), in stroke volume (-17.5%). No ECG
      changes were observed during that period. The haemodynamic changes observed do
      not differ from the published data in patients presenting for cardiac surgery and
      anaesthetized with manually controlled infusion techniques using propofol.

PMID- 11243015
TI  - [The effect of plasmapheresis and other immunomodulating therapies on the course
      of severe Guillain-Barre syndrome].
AB  - Clinical datas of 20 patients with severe Guillain-Barre syndrome were evaluated
      retrospectively. The diagnosis was established on the electrophysiological and
      histopathological examinations (electroneurography, electromyography, sural nerve
      and muscle biopsy) and the analysis of the cerebrospinal fluid. All of the
      patients were treated with plasma exchange and some of them with other
      immunomodulant therapies (intravenous immunoglobuline, steroid,
      cyclophosphamide), too. To judge the clinical state correctly we used the
      modified Rankin scale. The patient's follow up went on for maximum 4 years. The
      improvement was satisfactory in 7 cases (35%) and good in 6 patients (30%). The
      last 6 patients had pure motor neuropathy. Six patients (30%) remained in severe
      residual condition. All of them had long-term course of disease, serious sensory
      symptoms and predominantly axonal degeneration of the peripheral nerves. One
      patient had died. The plasma exchanges were well tolerated, without any serious
      adverse event. This therapy would be safe and effective help in Guillain-Barre
      syndrome.

PMID- 11243016
TI  - [Screening for carrier state of Haemophilia B using indirect genomic detection].
AB  - The authors report the first data having applied the indirect genomic diagnosis
      in carrier screening in Hungary. 22 patients with haemophilia B and female family
      members of 14 out of them were examined by PCR based restriction fragment length
      polymorphism analysis. The combined use of 3 intra- and 1 extragenic
      polymorphisms have been examined at the same population. DNA fragments,
      containing the single nucleotide change polymorphic site (Xmnl, Hhal, Taql), or
      the 50 bp insertion/deletion element (Dde) were amplified. The products were
      digested by the appropriate restriction digestion enzyme and were detected on
      agarose gel following ethidium-bromide staining. 20 siblings were interested in
      the determination of their carrier-state. 15 (75%) of them could get definite
      diagnosis. The carrier-state was established in 7 cases, excluded in 8 subjects.
      For the remaining 5 participants studied, the absence of the parental DNA sample
      caused uncertainty, while in 2 cases (10%) none of the analyzed RFLP was
      informative. The heterozygosity rate, the gene and haplotype frequency were also
      recorded and compared with the international data. The indirect methods have
      proved to be sufficient and well suitable for routine carrier testing. The
      results provide the basis of the subsequent prenatal diagnosis.

PMID- 11243017
TI  - [About paracetamol again].
AB  - The mechanism of hepatotoxicity caused by paracetamol (acetaminophen) overdose
      and the treatment of patients is reviewed. Paracetamol is widely used over-the
      counter drug with analgesic and antipyretic properties. Although it is considered
      to be safe at therapeutic doses, the incidence of hepatotoxicity caused by
      overdose or inadvertent application has been increasing lately. N-acetyl-p
      benzoquinonimine, one of the metabolites formed from paracetamol is responsible
      for the hepatotoxicity. Until now there is no complete therapeutic strategy for
      the effective treatment of hepatotoxicity caused by paracetamol. Gut
      decontamination, N-acetylcysteine antidote administration and enhancement of
      elimination is used for the management of paracetamol overdose. Those with severe
      hepatotoxicity and neurological symptoms can benefit from removal of necrotic
      liver and undergo transplantation.

PMID- 11243018
TI  - [Significance of hypothermic J-wave and the pertaining Hungarian literature].

PMID- 11243019
TI  - [Statistics of suicide in Hungary, 1970-1998].

PMID- 11243020
TI  - [Restricted antibody diversity after bone marrow transplantation--homogeneous
      immunoglobulins].
AB  - After bone marrow transplantation, a prolonged dysregulation of humoral immunity,
      including restricted electrophoretic heterogeneity of serum immunoglobulins and
      the appearance of homogeneous immunoglobulin components, can be observed. The
      current study was undertaken to characterize further and define the
      posttransplantational incidence of monoclonal and oligoclonal immunoglobulins, as
      well as the clinical and laboratory correlations of these phenomena. For this
      purpose, serial serum protein (IgM, IgG, IgA and CRP) quantification,
      electrophoresis and immunofixation were performed on 29 patients undergoing
      allogeneic bone marrow transplantation for chronic myeloid leukemia. 23 out of
      the 29 patients developed transient oligoclonal and/or monoclonal gammopathies
      that appeared between 20 and 1750 posttransplantational days. No correlation,
      however, between the development of graft versus host disease, EBV or CMV
      infections, or any other symptoms and development of homogeneous immunoglobulin
      components was seen. Therefore, the development of oligoclonal and monoclonal
      gammopathies after bone marrow transplantation may be an ubiquitous finding
      reflecting the inadequacy, i.e. oligoclonality of the recovering B-cell system.

PMID- 11243021
TI  - [Intraabdominal sclerosing panniculitis--myofibroblast proliferation that can
      mimic malignancy].
AB  - Intraabdominal sclerosing panniculitis is a fibroinflammatory lesion of the
      intraabdominal fat tissue of unknown origin. The authors report 4 secondary
      cases, that were associated with other kind of intestinal pathology. The cases
      had different clinical manifestation (mesenterial sclerosis leading to bowel
      obstruction, lesion simulating transmural spread or peritoneal metastasis of
      colorectal carcinoma, and chance finding associated with ulcerative colitis).
      They review the literature and summarize the features of the reactive process
      characterized by a spindle cell proliferation, fibrosis (sclerosis), chronic
      inflammatory infiltrate and fat necrosis. The immunohistochemical staining
      pattern of spindle cells favors a myofibroblastic origin. These cells, like cells
      of many other, but not all myofibroblastic lesions are CD-34 negative. The
      significance of recognizing the lesion as such is highlighted by the fact that
      the correct diagnosis has been seldom made without excision of the involved bowel
      segment. Theoretically surgical excision should be reserved for cases with bowel
      obstruction, or underlying pathology requiring this intervention. They believe
      that with awareness of the lesion secondary cases are not as rare as previously
      thought, although primary cases (those not associated with other intestinal
      pathology or specific etiologic agents) are only rarely encountered in everyday
      practice. They share the view that both primary and secondary cases are reactions
      to noxious agents, but this agent is unknown in primary cases.

PMID- 11243022
TI  - [Plasma homocysteine levels in hyperinsulinemic patients].
AB  - In order to evaluate the clinical characteristics of metabolic syndrome, a
      screening procedure was performed and in a cohort of middle-aged (40-60 years)
      hyperinsulinaemic (fasting plasma insulin > 15 microU/ml) and/or postprandial
      [120 min after 75 g glucose load] insulin > 45 microU/ml) subjects (n = 91;
      men/women: 38/53; age mean +/- SD 47.6 +/- 4.3 years; body mass index: 34.6 +/-
      4.9 kg/m2; waist-hip ratio: 0.92 +/- 0.07; actual blood pressure 146 +/- 16/87 +/
      9 mmHg; fasting insulin: 24.2 +/- 11.3 microU/ml; postprandial insulin 125.5 +/-
      103.8 microU/ml; serum LDL-cholesterol: 3.73 +/- 1.09 mmol/l; HDL-cholesterol:
      1.12 +/- 0.30 mmol/l; triglycerides: 2.97 +/- 2.38 mmol/l; uric acid 279 +/- 79
      mumol/l) plasma fasting homocysteine, vitamin B12 and folic acid levels were
      simultaneously determined. The values were separately evaluated according to the
      stages of glucose tolerance (normal glucose tolerance [n = 47]; impaired glucose
      tolerance [n = 24] and diabetes mellitus [n = 20]). Laboratory normal values were
      determined in 47 healthy subjects (control group, age: 45.0 +/- 7.8 years,
      men/women: 19/28). There was no significant difference between hyperinsulinaemic
      and control subjects regarding plasma homocysteine (9.28 +/- 3.81 mumol/l vs.
      9.63 +/- 2.70 mumol/l), folic acid (8.5 +/- 5.9 ng/ml vs. 7.5 +/- 2.1 ng/ml) and
      vitamin B12 levels (423 +/- 141 pg/ml vs. 356 +/- 121 pg/ml). Plasma homocysteine
      levels were significantly (p < 0.001) higher in hyperinsulinaemic men than women
      (11.34 +/- 4.72 mumol/l [n = 38] vs. 7.86 +/- 2.13 mumol/l [n = 53]). There was
      no significant difference between subgroups classified according to the stages of
      glucose tolerance in hyperinsulinaemic groups. Plasma homocysteine values
      exceeding the upper limit of normal range (> 12.45 mumol/l) were detected at a
      similar prevalence rate in control (4/47 = 8.5%) and in hyperinsulinaemic
      subjects (10/91 = 10.9%). A weak but statistically significant correlation was
      found between plasma homocysteine values and age of subjects (r = 0.222; p <
      0.05) whereas a stronger correlation was documented between plasma homocysteine
      and serum creatinine values (r = 0.658; p < 0.001) in hyperinsulinaemic groups (n
      = 91). Plasma homocysteine values independently from the stages of glucose
      tolerance are not elevated in hyperinsulinaemic subjects. Hyperhomocysteinaemia
      is not a characteristic feature of hyperinsulinism suggesting that plasma
      homocysteine levels are of no considerable importance in the complex
      pathomechanism of atherosclerosis at early stages of metabolic syndrome.

PMID- 11243023
TI  - [Effect of preparations combining trace-elements and vitamins on the frequency of
      illness among children attending kindergarten].
AB  - Between 17 January and 16 April 2000, 37 children attending a kindergarten were
      treated with MultiTabs masticatory tablets, product containing vitamins and trace
      elements. 36 children attending the same kindergarten served as controls. Only 1
      of the children participating in this multivitamin treatment required antibiotic
      treatment during this period, in contrast with 12 of the control group (3 of them
      on more than 1 occasion). It was interesting that, when they came into contact
      with subjects with chickenpox, only 11 of the 37 vitamin-treated children
      contracted this disease (the contagiosity index of which otherwise exceeds 90%).
      The increase in height of the treated children was significantly greater than
      that for the controls. Similarly between 17 January and 16 April 2000, 20
      children younger than 2 years (average age 16.6 +/- 5.5 months) participated in
      treatment with ACD drops (containing vitamins A, C and D). The controls here were
      20 infants of similar age (average 21.3 +/- 4.2 months) who participated in the
      traditional vitamin D treatment. None of the members of either group took part in
      child-community activities, but they all had siblings who attended kindergarten.
      Of the children receiving the ACD drops, 8 fell ill during the period in
      question, as compared with 12 of the controls. The number of days of illness per
      child was on average 3.6 in the treated group, and 6.5 in the control group.
      Three of the children receiving the ACD drops required antibiotic treatment,
      whereas this was necessary in 6 of the control children. The increases in both
      height and weight were significantly higher for those treated with the ACD drops
      than for the controls. No signs of rickets were observed in either group. The
      authors discuss the roles of the vitamins (A, D, E, B1, B2, B3, B6, B12, C, folic
      acid and nicotinic acid) and trace elements (Fe, Zn, Cu, Mn, I, Se and Cr)
      present in the multivitamin masticatory tablets in the maintence of human vital
      processes, and primarily in antioxidant processes and in the immune defence.

PMID- 11243024
TI  - [Ferenc Keresztury: from student at Sarospatak Russian medical professor (1735
      1811)].

PMID- 11243025
TI  - [The South-Pest Ferenc Jahn Hospital of the Capital Municipality].

PMID- 11243026
TI  - [Surgical treatment of lung diseases. 1900].

PMID- 11243027
TI  - [Obsessive-phobic disorders with the phenomena of mysophobia in slowly
      progressing schizophrenia].
AB  - 54 patients, 24 men and 30 women, (mean age 27 years) were examined. Two types of
      obsessive-phobic disorders with the phenomena of mysophobia were distinguished:
      obsession of the external (extracorporal) threat and obsession of contamination.
      Disorders of the first type (25 cases) were observed in psychopathic-like
      schizophrenia. They were characterized by a fear of possible contacts with
      different pathogenic agents--toxic substances, sharp small subjects, bacteria.
      Obsessions presented with a system of actions preventing phobic situations
      (rituals). With progression of the disease there was a decrease of both the
      degree and affective saturation of phobic disorders together with preserving
      rituals. Negative disorders presented with rough psychopathic-like changes with
      features of the "verschroben" defect. The disorders of the second type (29
      patients) were observed in neurosis-like schizophrenia. Mysophobia manifested
      with both the repeated control and the fear of contamination accomplished. Ritual
      behavior presented with repeated actions and repeated control of the "sterility"
      of the own body and the surrounding subjects. Dynamics of these disorders was
      characterized by a tendency to more severe rituals of the control and persisting
      anxiety. Deficit disorders manifested with mental infantilism with psychopathic
      like disorders of schizo-anancastic sphere. The above types of the obsessive
      phobic disorders have a differential-diagnostic significance in respect of
      clinical variations of schizophrenia and determination of the state acuity with
      possible reversibility of the disorders (in neurosis-like schizophrenia).

PMID- 11243028
TI  - [Clinical symptoms of schizophrenia in combination with delirium tremens].
AB  - In a group of 137 patients with schizophrenia combined with delirium tremens we
      also observed alcoholic hallucinosis (9.5%) and alcoholic paranoid (0.7%).
      Delirium tremens was more often observed in patients with schizophrenia in the
      following age groups: under 19 and of 20-29 years. Meanwhile, the frequency of
      the onset of the delirium tremens in a group of 2417 patients was higher in the
      age groups of 35-39 and 60 and over. In the main group of schizophrenic patients
      the rate of the onset of this endogenous disease was higher in the age groups of
      35-39, 40-44 and 50-54 years, as compared with a control group of schizophrenic
      patients (310 cases). The recurrent course of the disease was observed in these
      patients more often, whereas a continuous course was quite rare, as compared with
      a control group. Oneiroid states (9.5%) presented in some patients of the main
      group. Schizophrenic process was more favorable in combination with delirium
      tremens.

PMID- 11243029
TI  - [Clonazepam in therapy of neurogenic syncopal states].
AB  - 27 patients with frequent neurogenic syncopes (NS) resistant to conventional
      therapy were treated with clonazepam. The average age of the patients was 29.8 +/
      11.6 years. There were 1-2 syncopes in a month. Both before and after the
      treatment an active orthostatic test was performed with ECG registration and
      following analysis of variability of the cardiac rhythm. Clonazepam was
      administered in a dose of 2-2.5 mg/day during 8-9 weeks. Clinical improvement in
      the form of a lack of syncopes was observed in 20 patients (74%); 3 patients
      (10%) had isolated lipothymic states; 2 patients discontinued the treatment
      because of side-effects (dizziness). The results of the examination of 23
      patients 6 months after clonazepam therapy testified the stability of the
      therapeutic effect.

PMID- 11243030
TI  - [Comparative study of effects of ivadal and rodedorm in insomnia in structure of
      borderline mental diseases].

PMID- 11243031
TI  - [Non-uniform changes in EEG of patients with hemispheric stroke].

PMID- 11243033
TI  - [Plasticity in pathology of nervous system].

PMID- 11243032
TI  - [The role of magnetic resonance tomography in diagnosis of syringomyelia].
AB  - The paper presents the analysis of the results of the examination of 90 patients
      with syringomyelia using magnetic-resonance "Bruker" tomograph with the intensity
      of the magnetic field 0.23 T. The observation was carried out according to the
      authors' classification. Symptom complex of syringomyelia corresponding to the
      anatomic disorders of the spinal cord was described. The authors made a
      conclusion, that the magnetic-resonance tomography, as the most informative
      method, was a method of choice in syringomyelia. In 21% of the patients there was
      idiopathic syringomyelia; in 47.3% a process spread to the caudal regions of
      medulla oblongata. In 79% cases syringomyelia manifested as a syndrome; in 50% of
      the total cases it was found in Arnold--Chiari anomaly.

PMID- 11243034
TI  - [A case of late onset cerebrospinal meningovascular syphilis with amyotrophic
      lateral sclerosis syndrome].

PMID- 11243036
TI  - [A case of severe anorexia in a male patient].

PMID- 11243035
TI  - [Clinical and anatomical observation of mitochondrial encephalopathy].

PMID- 11243037
TI  - [The role of periventricular region of the brain in the genesis of the disorders
      of neurological development].

PMID- 11243038
TI  - [Somatized mental disorders].

PMID- 11243039
TI  - [A strategy for the quality evaluation of research publication in psychiatry].

PMID- 11243040
TI  - [Impairments of different kinds of memory in patients with ischemic stroke].
AB  - 27 patients aged 47-64 years with left hemispheric ischemic stroke with similar
      cognitive and educational levels were examined. Pharmacotherapy of the stroke
      directed to improvement of both memory and thinking was taken into consideration.
      To evaluate both different kinds of memory and a degree of the cognitive
      functions' impairments in the patients with a local ischemic stroke in anterior,
      posterior and middle parts of the left hemisphere the following tests were used:
      evaluation of both the immediate memory of the digits and the short-term audio
      verbal memory; short-term trials of the pathological action of interference;
      Benton test, Meily test; evaluation of the declarative, procedure, semantic,
      strategic, mediated, long-term kinds of memory. It is shown that remembering of
      the new information concerning verbal names, digits, was worse in mediobasal,
      frontal and temporal location of the stroke in the left hemisphere and depended
      on clinical manifestations of the disorders. The working semantic and strategic
      kinds of the memory were also damaged, while long-term memory (autobiographic,
      professional) was impaired in less degree.

PMID- 11243041
TI  - The IHS dental program--a historical perspective.
AB  - The federal government provides health services for American Indians and Alaska
      Natives based on treaties with tribes, legislation, and executive orders. These
      services began in the late 1700s, when they were the responsibility of the
      Department of War. This responsibility was later transferred to the Bureau of
      Indian Affairs and in 1955 the Indian Health Service was established within the
      United States Public Health Service. This paper describes the development and
      mission of the Indian Health Service dental program. During the 1950s, Public
      Health Service officers were assigned to the dental program, dental assistant
      training centers were established, and clinical prevention programs were
      implemented. Increased dentist recruitment, the implementation of four-handed
      dentistry, and the development of an automated information system were the
      highlights of the 1960s. Considerable effort was placed on work force development
      during the 1970s, while expansions of both treatment and prevention services were
      the highlights of the 1980s. Unfortunately, decreases in administrative staffing
      and a decline in clinical services have been noted during the last decade. The
      main reasons for the decline were initiatives to reduce the size of federal
      government and inability to recruit and retain dentists in clinical positions.
      Also, many tribes have elected to manage their own programs and have requested
      and received their share of IHS administrative funds to use in their programs.
      Recent pay and budget legislation along with changes in program management should
      reverse this trend.

PMID- 11243042
TI  - Prevalence and severity of dental caries among American Indians and Alaska
      Natives.
AB  - OBJECTIVES: This paper reports findings from the 1991 IHS Patient Oral Health
      Status and Treatment Needs Survey (1991 IHS patient survey) and presents trends
      in caries among American Indian and Alaska Native (Native American) populations
      since 1957. METHODS: The 1991 IHS patient survey obtained data from approximately
      10 percent (25,000) of the dental patients seen annually at IHS, tribal, and
      urban Indian clinics. The results of this survey are compared descriptively with
      previous surveys conducted by the IHS beginning in 1957. RESULTS: Findings from
      the 1991 IHS patient survey indicate that Native Americans experience a much
      higher prevalence of dental caries in their primary and permanent dentitions than
      the general US population. However, caries rates in Native American children
      peaked in 1983-84 and have been going down since that time. CONCLUSIONS: While
      progress has been made in preventing dental caries among Native Americans, the
      high prevalence and severity at all ages in this rapidly growing population have
      resulted in a large backlog of untreated disease with an overwhelming demand on
      the resources available to provide care. Continued emphasis on dental caries
      prevention and health promotion is an important part of the solution. New
      strategies such as targeting preventive services toward individuals and groups
      with the highest risk of disease and the use of modern conservative treatment
      methods to control disease must be employed. Full implementation of these
      strategies and identification of the resources required will depend upon new and
      ongoing partnerships among tribes, federal and state governments, and the private
      sector.

PMID- 11243043
TI  - Estimating dental treatment needs among American Indians and Alaska Natives.
AB  - OBJECTIVE: This paper describes the treatment needs of the American Indian and
      Alaska Native (Native American) population estimated from the 1991 Indian Health
      Service Oral Health Status and Treatment Needs Survey (1991 IHS patient survey).
      METHODS: The average per capita treatment need for the population is expressed
      both as the number of dental services and clinical time required to provide these
      services. Values for service minutes also are used to compare treatment needed
      with the treatment provided. RESULTS: The need for dental care is greatest among
      adults aged 25-54 years. We anticipate that needs will increase with population
      growth and as teeth are retained longer. Large amounts of dental needs go unmet
      each year in the Native American population: because resources are not available
      to provide all needed care, dental services are prioritized and rationed. The
      basic premise upon which care is rationed is changing from basic care for all who
      have access, to more complex care for fewer individuals. This trend may be driven
      by the opportunity to generate third party revenue offered by more complex
      procedures. CONCLUSION: Evaluation is needed of the effects of new approaches on
      oral health and access to dental care.

PMID- 11243044
TI  - A review of the oral health of American Indian and Alaska Native elders.
AB  - OBJECTIVES: This paper reviews the demographics, access to care barriers, and the
      oral health of American Indian and Alaska Native (Native American) elders aged 65
      years and older using complete tooth loss as a measure to compare with the US
      population. Strategies for improving oral health and increasing access to care
      for Native American elders also are discussed. METHODS: We reviewed the results
      from patient surveys conducted by the Indian Health Service (1983-84 and 1991)
      and data from other sources, including the second International Collaborative
      Study of Oral Health Outcomes (ICS-II) conducted in 1990 on the Sioux and Navajo
      reservations. We compared complete tooth loss data from these studies with
      findings of the 1985 National Institute of Dental Research Oral Health Survey of
      US Employed Adults and Seniors and the Third National Health and Nutrition
      Examination Survey (NHANES III). RESULTS: The 1991 Indian Health Service (IHS)
      patient survey reported a complete tooth loss prevalence of 42 percent among
      elders. Although it is based on a patient sample, this finding is comparable to
      the rate of 40 percent found among a random sample of Navajo and Lakota adults
      aged 65-74 years reported in the ICS-II study. The 1991 IHS patient survey also
      found complete tooth loss among diabetics to be much higher than among
      nondiabetics. CONCLUSIONS: The prevalence of complete tooth loss for Native
      American elders is higher than in population surveys of US elders based on random
      samples. The actual prevalence of complete tooth loss is probably even higher in
      Native American elders because estimates presented in this paper are clinic
      based.

PMID- 11243045
TI  - Periodontal disease in American Indians and Alaska Natives.
AB  - OBJECTIVE: The primary purpose of this paper is to provide information on the
      periodontal disease status of Native Americans using a variety of data sources.
      The impact of periodontal disease on the provision of dental care within the
      Indian Health Service (IHS) is also discussed. METHODS: Four data sources were
      used to evaluate the periodontal disease status of Native Americans: IHS
      periodontal disease monitoring system (1962-78), 1984 IHS Patient Oral Health
      Survey, 1990 WHO community-based survey (ICS-II), and the 1991 IHS Patient Oral
      Health Survey. RESULTS: There appears to be a trend toward a higher prevalence of
      incipient and overt periodontal disease among Native Americans over time. The
      prevalence of overt periodontal disease (periodontal pockets > 5.5 mm) is higher
      among Native American diabetic patients than nondiabetic patients (34% vs 19%).
      CONCLUSIONS: Due to the variety of indices used by the IHS during the last 20
      years, it is difficult to make direct comparisons of the available periodontal
      disease data. However, it appears that the prevalence of periodontal disease
      among Native Americans is increasing. Type II diabetes accounts for significant
      increases in periodontal disease and tooth loss in Native American populations.
      Certain forms of early onset periodontal disease also may pose significant
      threats to the oral health of Native Americans.

PMID- 11243047
TI  - Successful aging: implications for oral health.
AB  - The past few years have seen a growing emphasis in gerontology on the concept of
      "successful" or "robust" aging. This represents a major paradigm shift in the
      field from a focus on declines in physical and social functioning, assumptions of
      the aging process as a downward spiral, and studies on how to manage these
      declines. Leading the way toward this new perspective on aging, the MacArthur
      Studies of Successful Aging asked the fundamental question: "What genetic,
      biomedical, behavioral, and social factors are crucial to maintaining health and
      functional capacities in the later years?" These studies examined longitudinally
      a large cohort of independent elders on several physical, cognitive, emotional,
      and social parameters. Other researchers have focused on the theme of robust
      aging; however, common predictors have emerged, such as remaining active
      physically and cognitively, maintaining social contacts, and avoiding disease.
      This research is timely, given the expanding population of the oldest old, and
      with successive cohorts demonstrating the "compression of morbidity" phenomenon.
      Such a paradigm shift is critical in geriatric dentistry as well, where
      successful aging is evident in the growing number of older adults who have
      retained their natural dentition into advanced old age. This presentation draws
      parallels between successful aging at the systemic and oral health levels, with
      illustrations from epidemiologic studies that demonstrate trends in improved
      health and quality of life among newer cohorts of older adults.

PMID- 11243046
TI  - Tooth loss and need for extractions in American Indian and Alaska Native dental
      patients.
AB  - OBJECTIVE: This article reports results of the 1991 Indian Health Service Patient
      Oral Health Survey in the areas of tooth loss and need for tooth extraction.
      METHODS: The survey examined a sample of American Indian and Alaska Native dental
      patients. Tooth loss and need for tooth extraction are explored for a total of
      12,349 individuals aged 18 years and older. RESULTS: Complete tooth loss in
      patients aged 35 years and older was 11 percent; in patients aged 65 years and
      older, it was 42 percent. The mean number of remaining teeth in dentate patients
      aged 35 years and older was 20.7; the mean number of remaining teeth decreased in
      each older age group. Partial and complete tooth loss were more severe in
      diabetic patients. In 35- to 44-year-old patients, only 20 percent had not lost
      at least one permanent tooth. The prevalence of tooth loss differs by geographic
      region. The percentage of dental patients with 20 or more teeth increased between
      1984 and 1991. CONCLUSION: Tooth loss remains a substantial problem in American
      Indian and Alaska Native adult dental patients. This article presents results of
      an Indian Health Service (IHS) oral health survey conducted in 1991 of the
      American Indian and Alaska Native (Native American) population with respect to
      tooth loss. Limited comparisons of tooth loss observed in the 1991 patient survey
      are made to the 1984 patient survey.

PMID- 11243048
TI  - Demonstrating successful aging using the International Collaborative Study for
      Oral Health Outcomes.
AB  - As the lifespan increases and people are faced with 15 to 20 years of "old age,"
      we ask what one considers successful aging with respect to oral health. We
      propose a comprehensive combination of outcome variables, maintenance of teeth,
      manageable periodontal condition, positive perceived oral health, satisfaction
      with their access to and receipt of dental services, and minimal functional
      problems, that together comprise a definition of successful aging. The
      International Collaborative Study for Oral Health Outcomes provides a data set
      for exploring the oral health of a diverse sample of older adults in US and
      international sites using the modified Andersen Behavioral Model. The percent of
      adults who report no natural teeth ranged from 16 percent in San Antonio to 59
      percent in New Zealand. Seventy percent or more of the adults from each site
      rated their oral health as good/fair or better except in Poland. The current
      cohort of older adults is faring better on some indicators than others;
      nevertheless, ethnic minorities and poorer countries still demonstrate
      inequities. Dentistry must attempt to educate individuals early in their lifespan
      that a combination of personal oral health practices and current dental
      techniques offers the potential for successful oral health throughout one's
      lifetime.

PMID- 11243049
TI  - Systemic diseases and their treatments in the elderly: impact on oral health.
AB  - The lifespan of the US population is increasing, with the elderly desiring
      successful aging. This goal is jeopardized as multiple systemic conditions and
      their treatments become more prevalent with age, causing impaired systemic and
      oral health and influencing an older person's quality of life. To obtain
      successful aging, a compression of morbidity must be obtained through prevention
      and management of disease. This paper describes the most common systemic diseases
      causing morbidity and mortality in persons aged 65+ years: diseases of the heart,
      malignant neoplasms, cerebrovascular diseases, chronic obstructive pulmonary
      disease, pneumonia, influenza, diabetes mellitus, trauma, Alzheimer's disease,
      renal diseases, septicemia, and liver diseases. Disease prevalence and the impact
      of medications and other therapeutic measures used to treat these conditions are
      discussed. Oral sequelae are reviewed with guidelines for early detection of
      these deleterious consequences, considerations for oral treatment, and patient
      management. An understanding of the impact of systemic diseases and treatment on
      oral health is imperative for dental practitioners to appropriately treat and
      manage older patients with these conditions. With a focus on early detection and
      prevention, oral health care providers can improve the quality of life of this
      population and aid in the attainment of successful aging.

PMID- 11243050
TI  - Sensory and motor deficits in the elderly: impact on oral health.
AB  - Hearing, vision, orthopedic, and speech disorders are the most common impairments
      in the elderly. Older adults experience other sensory impairments such as
      olfactory and gustatory dysfunction, as well as oral motor problems including
      difficulty with mastication, speech, and swallowing. These disorders can directly
      affect oral health and can impair dental treatment. Therefore, it is imperative
      that dental health practitioners be cognizant of these conditions and aware of
      the impact these conditions and their treatments can have on oral health and
      function. Dental professionals may need to use different communication techniques
      for patients with vision or hearing losses. Accommodations in the dental office
      and by dental professionals will help older patients who have sensory and/or
      motor impairments to preserve their oral health and function and receive dental
      treatments in a safe and efficacious manner. This paper reviews the most common
      causes of sensory and motor impairments and their implications for oral health
      care with treatment modification guidelines for the older patient.

PMID- 11243051
TI  - Oral health and nutrition in older people.
AB  - The theoretical link between foods choice and masticatory efficiency has long
      been established. Recent evidence has confirmed this association, demonstrating a
      progressive alteration in food choice with decreasing numbers of teeth, with the
      greatest effect being among those who are edentulous. This altered food selection
      results in significant differences in the hematological status for some key
      nutrients in the one study in which this association was investigated. This paper
      summarizes some of the literature relevant to diet as a risk factor for systemic
      disease and identifies areas where altered food choice as a consequence of
      reduced masticatory efficiency might be placing individuals at increased risk of
      life-threatening conditions, such as atherosclerosis and cancer.

PMID- 11243052
TI  - Successful aging--the case for prosthetic therapy.
AB  - Reduced chewing ability in community-dwelling older people is linked to the
      presence of removable dentures and having fewer than 20 natural teeth present.
      Compensation is provided by chewing longer and swallowing larger food particles.
      Replacement of posterior tooth loss by fixed or removable prostheses increases
      the activity of the masticatory muscles, and reduces chewing time and the number
      of chewing strokes until swallowing. In residents of nursing homes and long-term
      care facilities undernutrition is prevalent because of general medical problems,
      reduced appetite, and poor quality of life. Poor oral health and xerostomia are
      often present and may have a negative effect on masticatory function and
      nutrition, precipitating avoidance of difficult-to-chew foods. There is no
      evidence that the provision of prosthetic therapies can markedly improve dietary
      intakes; however, it might improve oral comfort and quality of life and avoid
      enteral alimentation.

PMID- 11243053
TI  - Impact of oral diseases on systemic health in the elderly: diabetes mellitus and
      aspiration pneumonia.
AB  - Evidence is increasing that oral health has important impacts on systemic health.
      This paper presents data from the third National Health and Nutrition Examination
      Survey (NHANES III) describing the prevalence of dental caries and periodontal
      diseases in the older adult population. It then evaluates published reports and
      presents data from clinical and epidemiologic studies on relationships among oral
      health status, chronic oral infections (of which caries and periodontitis
      predominate), and certain systemic diseases, specifically focusing on type 2
      diabetes and aspiration pneumonia. Both of these diseases increase in occurrence
      and impact in older age groups. The NHANES III data demonstrate that dental
      caries and periodontal diseases occur with substantial frequency and represent a
      burden of unmet treatment need in older adults. Our review found clinical and
      epidemiologic evidence to support considering periodontal infection a risk factor
      for poor glycemic control in type 2 diabetes; however, there is limited
      representation of older adults in reports of this relationship. For aspiration
      pneumonia, several lines of evidence support oral health status as an important
      etiologic factor. Additional clinical studies designed specifically to evaluate
      the effects of treating periodontal infection on glycemic control and improving
      oral health status in reducing the risk of aspiration pneumonia are warranted.
      Although further establishing causal relationships among a set of increasingly
      more frequently demonstrated associations is indicated, there is evidence to
      support recommending oral care regimens in protocols for managing type 2 diabetes
      and preventing aspiration pneumonia.

PMID- 11243054
TI  - The delivery of oral care services to elderly people living in a
      noninstitutionalized setting.
AB  - Advances in medical science are enabling people to survive more illness and
      disability. As people live longer, their mobility and/or ability for self-care
      often are reduced by physical or mental disability and other chronic diseases. It
      may become unreasonable or impractical for them to access mainstream dental
      services. Increasing numbers of dentate elderly people with expectations of oral
      health higher than earlier cohorts of elderly people are likely to bring
      increasing demands to the dental profession for their continuing care. Thus, the
      oral care for disabled elderly people in noninstitutionalized settings may pose a
      challenge. The oral care options available to this group of people include the
      dental surgery/operatory, a mobile dental service, home-based or domiciliary
      dental care, a mix-and-match combination of surgery-based and domiciliary care,
      and cyberspace. Noninstitutionalized, disabled elderly people may have to rely on
      domiciliary care services for their oral health care. This paper explores the
      training implications, the necessary knowledge and skills base, the benefits and
      limitations to both the service provider and user, the equipment available, and
      the cost/funding of domiciliary dentistry. Domiciliary dental care services need
      to be developed by improving pre- and postdoctoral training programs and by
      establishing realistic remuneration for dental teams providing this care so that
      noninstitutionalized, disabled elderly people can access oral health care.

PMID- 11243056
TI  - Target outcomes for long-term oral health care in dementia: a Delphi approach.
AB  - This study developed a list of target outcomes for long-term oral health care in
      persons with dementia. A three-round Delphi study was used to develop a list of
      target outcomes. Participants included 99 staff and 171 family members associated
      with the Dementia Special Care Unit in Bedford, MA. In Round 1 participants were
      asked to list five outcomes for long-term oral health care. Items were grouped,
      redundancies removed, and fed back in Round 2, when participants scored the items
      from 1 (least important) to 10 (most important). Round 2 responses were tabulated
      and the top 20 were fed back for scoring in Round 3. The top 10 target outcomes
      in decreasing order of importance were: patient will be free from oral pain,
      patient will not be at risk for aspiration, emergency dental treatment will be
      available when needed, prevent mouth infections, daily mouth care is as much a
      part of daily care as shaving or brushing hair, prevent discomfort from loose
      teeth or sore gums, teeth will be brushed thoroughly once a day, staff will be
      able to provide oral hygiene care as needed, provide dental care to prevent
      problems eating, and recognize oral problems early. Family and professional
      caregivers were remarkably consistent in their identification of the top 10
      outcomes. Further work is needed to ensure broad international and
      interdisciplinary acceptance (including families and the long-term care residents
      themselves) of target outcomes for long-term oral health care in persons with
      dementia.

PMID- 11243055
TI  - Oral care for successful aging in long-term care.
AB  - The oral health of frail elders residing in long-term care facilities is very
      poor, probably because access to dental services is limited and help with daily
      mouth care is almost nonexistent. Recent concerns and interest have been raised
      through the cooperation of administrators, nursing staff, and dental personnel to
      address this apparent neglect. Moreover, evidence shows that caries and
      periodontal disorders can be managed successfully in geriatric populations.
      Consequently, there is a basis on which to develop a practical strategy for mouth
      care that should reduce the morbidity and early mortality in long-term care and
      to assist an increasingly frail and dependent population to age successfully.

PMID- 11243057
TI  - Public policy on oral health and old age: a global view.
AB  - This paper reviews major trends in the global demography and oral health status
      of populations, the challenges faced in ensuring successful aging because of
      these trends, and basic principles to guide public policy responses. Virtually
      all populations in which the dental caries prevalence reached high levels in the
      first half of the 20th century have experienced large reductions. A feared
      increase of the disease in the developing world has been far less than expected.
      Some countries that did suffer large increases dating from the 1960s already have
      managed to return to their former low levels because of timely use of preventive
      measures. Improving oral hygiene and a consequent reduction in the occurrence and
      severity of periodontal diseases further bolster the mainly positive trend in
      global oral health. Only in the former socialist economies is oral health status
      worsening. These positive changes have brought the expectation that an intact and
      well-functioning dentition should last for life, no matter how extended the
      lifespan becomes. But these changes take us into "uncharted waters" and the most
      appropriate strategies for preserving health in old age are unknown because they
      have never been tried. However, public policies to support community awareness
      and acceptance of broad-based preventive behaviors to preserve oral health in old
      age are essential. Policies also must provide guidance on how to proceed when
      disabling disease occurs, provide for regular research and updating of
      information, and ensure access to cost-effective and high-quality services for
      all.

PMID- 11243058
TI  - Introduction of red palm oil into the 'ready to eat' used supplementary feeding
      programme through ICDS.
AB  - Children attending the anganwadi centres were fed with Ready to eat (RTE) food
      containing 2g of Red Palm Oil (RPO). Daily children's attendance, their
      participation in the feeding programme, quantity of food supplement consumed were
      recorded. Heights, weights, clinical signs of vitamin A deficiency and morbidity
      pattern of the beneficiary children were assessed. There was increase in
      attendance of the children in the feeding programme after introduction of RPO.
      Quantity of the food supplement consumed by the children also increased. An
      improvement in the nutritional grades of children was observed. Signs of vitamin
      A deficiency were absent. Anganwadi teachers, helpers and parents accepted the
      inclusion of RPO in the supplementary feeding programme.

PMID- 11243059
TI  - The utility of waist circumference in assessment of obesity.
AB  - The objective of this study was to assess the correlation between waist
      circumference and waist hip ratio and body mass index. Also to assess if a simple
      measurement like the waist circumference can be used as an independent indicator
      for detecting health risk and management. 500 men and 500 women were included in
      this study from the out patient department and indoor wards of Medical College,
      Calcutta. Only 7% of the males and 16% of the females had body mass index > or =
      25. About 50% of both males and females had waist hip ratio above the desirable
      range (0.80 for females and 0.95 for males). About 99% of females with, waist
      circumference > or = 72 cm. had either body mass index > or = 25 or high waist
      hip ratio > or = 0.80 or both. Similarly 99% of males with waist circumference >
      or = 80 cm. had either high body mass index > or = 25 or high waist hip ratio >
      or = 0.90 or both. Waist circumference is simple to assess and can be used as an
      independent measurement to identify those at risk from either increased body
      weight or central fat distribution or both.

PMID- 11243060
TI  - Influence of recall period on estimates of diarrhoea morbidity in infants in
      rural Tamilnadu.
AB  - Data collected on 689 infants, in a study to assess the incidence of diarrhoea
      and acute respiratory infections during infancy, is used here to quantify the
      extent of under-reporting in diarrhoea morbidity surveys. The study area
      consisted of two contiguous primary health centres in Villupuram health unit
      district in Tamil Nadu, South India. Each day of infancy was assigned a recal
      period and proportion of diarrhoeal days for various recall period computed. The
      proportion of diarrhoea was 11.3%, 12.0% and 11.2% for zero, one and two days of
      recall period, respectively, after which the proportion decreased. The under
      reporting of diarrhoea was approximately 15%, 26% and 45% with three, six and 7
      13 days of recall period, respectively. As there is considerable under-reporting
      of diarrhoea morbidity when recall period exceeds three days, it would be best to
      collect information on diarrhoea at least twice a week in diarrhoeal morbidity
      surveys.

PMID- 11243061
TI  - A qualitative assessment of ante-natal care provided by auxillary nurse midwives.
AB  - Two hundred sixty eight antenatal mothers were observed for the quality of
      services provided by Auxillary Nurse Midwives (ANMs). History taking was found to
      be satisfactory in only 2.6% women. Obstetric examination was done
      unsatisfactorily in majority (52.6%) of the mothers. General physical examination
      was not done in 69% women. ANMs in all 31 sub-centres were not performing
      investigation like haemoglobin estimation, urine testing, foetal heart sound
      monitoring and blood pressure recording.

PMID- 11243062
TI  - Practice of prelacteal feeding in a rural community.
AB  - In India breast feeding in rural areas appears to be shaped by the health beliefs
      of a community, which are further influenced by social, cultural and economic
      factors. One of such tradition is prelacteal feeding which is widely prevalent
      since ancient times. The present study was aimed to find out the practice of
      prelacteal feeding and various factors which influence this practice. The study
      on analysis showed that 45% (90) mothers gave prelacteal feeds to their newborns
      in the form of sugar water, gur water or cow's milk. Sugar water was common
      amongst mothers belonging to nuclear family (49%) whereas gur water was given
      mostly by joint family mothers (75.70%). Parity and family type had no
      significant effect on this practice, however the effect of literacy was found to
      be significantly related to the practice.

PMID- 11243063
TI  - Sociomedical correlates of missed opportunities for immunisation.
AB  - Missed opportunity for immunisation is one of the hurdles in the achievement of
      85 percent or more immunisation coverage. It is essential to screen every child
      for immunisation status and advise necessary immunisation at every opportunity
      otherwise full immunisation coverage may not be possible. Present survey was
      carried out at Indira Gandhi Medical College and Hospital, Nagpur to study the
      sociomedical correlates of missed opportunities for immunisation in children
      below 2 years of age attending the hospital. Missed opportunities for
      immunisation in these children was found to be 39.9%. It is mostly for B. C. G.
      (21.8%) and measles (9.8%) and maximum for booster doses of DPT and polio (43%).

PMID- 11243064
TI  - Differential efficacy evaluation of formulations of Bacillus thuringiensis Var
      israelensis against mosquitoes: a laboratory investigation.
AB  - The efficacy evaluation of three formulations; wettable powder (W.P.) floating
      pellet and beads of Bacillus thuringiensis Var israelensis (Bti), revealed a
      greater susceptibility of the early larval instars of mosquitoes to Bti,
      sensitivity of anophelines to floating pellet, culicines to bead and equal
      efficacy and faster kill of W.P. to all the mosquitoes tested. A greater
      persistence of the slow release formulations, floating pellet and beads for 49
      and 28 days against anophelines and culicines respectively was observed in
      contrast to a maximum persistence for 21 days in case of W.P. formulation.

PMID- 11243065
TI  - Descriptive epidemiology of acute respiratory infections among under five
      children in an urban slum area.
AB  - A study was conducted in Sunderpur, Varanasi to study the magnitude of the
      problem of acute Respiratory Infections among under five children in an urban
      slum and the clinical profile of it in order to understand the pattern of disease
      presentation for identifying methods of early diagnosis and timely intervention.
      150 under five children were selected by stratified random sampling method and
      were observed for 52 weeks at weekly interval to record the illnesses. In total
      661 episodes were observed in 5623 child-weeks of observation giving an episode
      rate of 6.11 per child per year. ARI accounted for 67% of all morbidities. Mean
      duration of all the episodes taken together was 8.15 + 5.44 days. Majority of the
      episodes (88.96%) were confined to the Upper Respiratory Tract only. Most
      commonly occurring clinical features were rhinorrhea, nasal stuffiness and cough.
      61.4% of all the episodes terminated within seven days, and only 26.2% continued
      for two weeks.

PMID- 11243066
TI  - Environment and diarrhoeal diseases: a public health perspective.

PMID- 11243067
TI  - Estimated costs of acute adenolymphangitis to patients with chronic
      manifestations of bancroftian filariasis in India.
AB  - In India, lymphatic filariasis persists as a major cause of clinical morbidity
      and as an impediment to socio-economic development. The direct costs incurred for
      the treatment of adeno-lymphangitis (ADL) episodes and the consequent indirect
      costs due to loss of income were determined from selected agricultural labour
      intensive rural endemic pockets in Tamil Nadu. Information on the occurrence of
      ADL, its frequency and duration were collected using semi-structured
      questionnaire from randomly selected patients afflicted with chronic
      manifestations of bancroftian filariasis. Direct (treatment) cost per year per
      patient was found to range from Rs. 30 to 101 among patients with different
      manifestations. Income foregone (indirect cost) annually by each patient, which
      is a function of frequency and duration of ADL ranged from Rs. 182 to 702. ADL
      episodes among filarial patients alone cost a minimum of Rs. 4515 million for the
      nation every year. Cost benefit analysis of filariasis control programme in India
      showed that the benefits in terms of savings on treatment and work lost due ADL
      alone exceeded the cost by 24%. The per capita cost of the National Filaria
      Control Programme was calculated to be Rs. 2.6 per annuam.

PMID- 11243068
TI  - Paediatric inpatient morbidity patterns and drug usage in a teaching hospital
      serving an underdeveloped area.
AB  - Morbidity patterns and drug usage in hospitalized children in a developing area
      were prospectively studied. The study group consisted of 347 children (age 0-12
      yrs) representing all admissions to a paediatric unit over a six month period.
      Respiratory tract diseases (30.5%) and infectious diseases (26.1%) were the most
      common reasons for hospitalization. Tuberculosis was the most common infectious
      disease seen among the hospitalized children. Antimicrobials (60.8%), iron
      preparations (45.5%), vitamins (43.2%) and antipyretics (29.9%) were the most
      frequently prescribed groups of drugs. Ampicillin was the most commonly used
      antimicrobial. Adverse drug reactions were seen in 1.7% of the children. The
      overall mortality was 9.2%. The mean length of stay was 7.9 days and the mean
      number of drugs used was 3.4 per patient. More than 4 drugs were prescribed in
      54.4% of children. Approximately two thirds received parenteral therapy.

PMID- 11243069
TI  - Perceptions on effects of environmental pollutants in Hyderabad City.
AB  - Five hundred twenty adults were interviewed on the perceptions of effects of the
      environmental pollutants in Hyderabad city of Andhra Pradesh. The information was
      gathered on polluted water, polluted air, solid wastes, food contamination and
      readiness to participate in corrective actions. Both initial response and
      response after probing were recorded. Analysis was done basing on the level of
      literacy. The correct initial responses on effects of pollutants ranged from 28.3
      to 35.4% while responses after probing ranged from 79.2 to 88.1%. 45.8% were
      ready to participate manually in the corrective actions while 24.6% were eager to
      contribute financially in remedial actions. The study reveals the need for the
      initiation of aggressive environmental education.

PMID- 11243070
TI  - Possibility of public health hazards by contamination of toxin producing Vibrio
      cholerae through fishes reared in sewage fed fishery.
AB  - This study was undertaken to explore the possibility of contamination of Vibrio
      cholerae serogroups 01 and 0139, the most important causative organisms for life
      threatening acute secretory diarrhoea and also potential public health
      importance, by isolating these organisms from body surface, gill and intestine of
      common table fishes like Labeo rhoita, Catla Catla, Cirrhinus mirgala and Tilapia
      mosambica which were reared in sewage and raw human excrita enriched fishery
      ponds. Vibrio Cholerae 01 or 0139 were not isolated from body surface swabs,
      gills and intestine of these common table fishes. Water samples of sewage
      enriched fishery ponds and sewage of Calcutta municipal corporation were also
      processed for isolation of these organisms, however, these samples were also
      negative for V. Cholerae 01, 0139 and non 01-0139 serogroups. Present study
      indicated that there was less chance of contamination of toxigenic and disease
      producing strains of V. cholerae by common table fishes which were reared in
      sewage and raw faecal matter enriched fishery ponds.

PMID- 11243071
TI  - Risk factors of acute respiratory infections in underfives of urban slum
      community.
AB  - To ascertain the risk factors of Acute Respiratory Infections (ARI) in children,
      a prospective study was conducted for a period of one year among 112 underfives
      in urban slum community of Calcutta. Incidence of ARI was found significantly
      higher in undernourished children of poor socio-economic class. Parental smoking
      habit and solid fuel use for cooking were recognised as important risk factors of
      ARI.

PMID- 11243072
TI  - Post exposure rabies prophylaxis with Purified Verocell Rabies Vaccine: a study
      of immunoresponse in pregnant women and their matched controls.
AB  - The present controlled clinical trial evaluates the immunoresponse to Purified
      Verocell Rabies Vaccnine (PVRV) by Essen schedule of vaccination during
      Pregnancy. Seventeen Pregnant women with history of animal bites who received
      PVRV as per Essen regimen were matched for the confounding variables of age,
      socio-economic status and doses of PVRV received with seventeen "Non-pregnant
      women". The mean age was about 24 years, majority (70.6%) belonging to middle
      socio-economic group and received 3 doses of PVRV. Contrary to the expectations
      the rabies neutralizing antibody titres were slightly higher in pregnant women
      (except day 180) but the difference was not significant (P > 0.2). Both the
      groups of women had antibody titres above protective level (0.5 IU/ml) from day
      14 till day 365 thus indicating immunogenic efficacy of PVRV by Essen regimen
      during Pregnancy.

PMID- 11243073
TI  - Effectiveness of training on the knowledge of vitamin A deficiency among
      Anganwadi workers in a rural area of north India.
AB  - Training of 95 Anganwadi workers (AWW) were done in two groups in a rural block
      of Haryana State, India to impart knowledge on vitamin A deficiency (VAD) through
      lecture, demonstration, discussion. In group A consisting of 56 AWW townom
      coloured film slide was shown while in group B consisting of 39 AWW no film slide
      was shown. During pre-test 90.5% participants had medium score with an overall
      mean (+/- SD) score of 14.1 (+/- 3.0). Post-test conducted after 6 months showed
      a significant increase in knowledge of AWW regarding VAD with a mean score of
      20.3 (+/- 4.51), (P < 0.01). Mean score of group A [22.5 (+/- 4.04)] was
      significantly higher than mean score of group B [17.4 (+/- 3.5); P < 0.05]. This
      study reveals the need for in-service training of AWW using appropriate teaching
      methods incorporating audio-visual aids like film slide show for control of VAD.

PMID- 11243074
TI  - Incidence of meningitis in Manipal.
AB  - One thousand one hundred and seventy cerebro spinal fluid (CSF) samples from
      clinically diagnosed meningitis patients were subjected to macroscopic and
      microscopic examination. CSF samples were also cultured. Five percent CSF samples
      were positive for bacterial (4.3%) and fungal (0.7%) organisms. Gram positivity
      was observed in 6.4% samples. The percentage of bacterial isolates was highest in
      newborn and infants (6.1%) and (4.3%) in patients of 1-12 years age group.
      Cryptococcus species were isolated from 8 adult patients. Among Gram positive
      bacterial isolates, coagulase negative Staphylococci was highest (8%), followed
      by Pneumococci (6%) and B-haemolytic Streptococci (2%). Among Gram negative
      bacilli, Pseudomonas aeruginosa was predominant (42%) followed by Klebsiella
      species (20%) though Klebsiella was predominant in newborns and infants.

PMID- 11243075
TI  - Increasing prevalence of HIV-2 and dual HIV-1-2 infections among patients
      attending various outdoor patient departments in Mumbai (Bombay).
AB  - Between 1993-96, a serological study was carried out for differentially
      identifying HIV-1 and HIV-2 infections among the high risk group persons
      attending the various outdoor patient departments of BYL Nair Municipal Hospital,
      Mumbai. This study indicates that although HIV-1 is still the predominant virus
      among the high risk HIV infected persons in Mumbai, dual HIV-1-2 infections are
      increasing especially among promiscuous heterosexuals and female commercial sex
      workers. Increases in HIV-2 infections were observed later than dual HIV-1-2
      infections, indicating that it is the HIV-1 infected individuals who through
      continued high risk behavior got infected by HIV-2.

PMID- 11243077
TI  - A community based study on health impact of flood in a vulnerable district of
      West Bengal.
AB  - In order to ascertain the disaster vulnerability and health risks of flood in
      Hooghly district of West Bengal, this community based study was conducted through
      record analysis, interview of concerned authorities and household survey of
      morbidities before and after flood. Two blocks, with most of its population, were
      found to be the worst affected among all the disaster vulnerable blocks of the
      district. Incidence of diarrhoea, other enteric diseases and respiratory
      infections were significantly higher (P < 0.05) among the population in flood
      affected blocks, compared to the unaffected. The attack rate of diarrhoea in the
      flood affected population had increased significantly following flood (P < 0.05).

PMID- 11243076
TI  - Field investigaton of an outbreak of epidemic dropsy in eastern Nepal.
AB  - About 17 cases with clinical syndrome suggestive of epidemic dropsy attended to
      the B P Koirala Institute of Health Sciences, Dharan, for treatment. These cases
      were from three villages of Saptari district in eastern Nepal. Some of the
      mustard oil samples were tested positive with Nitric acid test. In the wake of
      this, an extensive field investigation was conducted covering a wider area in
      these villages.

PMID- 11243078
TI  - Seropositivity of Toxoplasma gondii in domestic animals.
AB  - Serum samples from 107 goats, 40 sheep, 50 cows were tested for Toxoplasma gondii
      antibody by indirect haemagglutination test (IHA) in dilutions of 1:10, 1:54,
      1:162 and 1:486. Toxoplasma gondii-antibodies were found in 21 (19.6%), 10 (25%),
      26 (52%), goat, sheep and cow sera respectively. No serum sample showed a titre
      higher than 1:162. All animals were kept in good hygienic condition. These
      results indicate that Toxoplasma gondii antibodies are widespread in animal
      populations which supports that toxoplasmosis is a widely spread zoonotic
      infection in this country.

PMID- 11243079
TI  - Malnutrition: a silent emergency.

PMID- 11243080
TI  - Case study of a lactating grandmother.

PMID- 11243081
TI  - Nutrition--an Indian perspective.

PMID- 11243082
TI  - Nutrition status of children and women in West Bengal--challenges and
      opportunities.

PMID- 11243083
TI  - Integrated Child Development Services scheme (ICDS) and its impact on nutritional
      status of children in India and recent initiatives.
AB  - Integrated Child Development Services (ICDS) scheme is the largest national
      programme for the promotion of the mother and child health and their development
      in the world. The beneficiaries include children below 6 years, pregnant and
      lactating mothers, and other women in the age group of 15 to 44 years. The
      package of services provided by the ICDS scheme includes supplementary nutrition,
      immunization, health check-up, referral services, nutrition and health education,
      and pre-school education. The distribution of iron and folic acid tablets and
      megadose of vitamin A is also undertaken, to prevent iron deficiency anaemia and
      xerophthalmia respectively. The scheme services are rendered essentially through
      the Anganwadi worker (AWW) at a village centre called "Anganwadi". The ICDS had
      led to (i) reduction in prevalence of severe grades of malnutrition and (ii)
      better utilization of services of national nutritional anaemia prophylaxis
      programme and the national programme for prevention of nutritional blindness due
      to vitamin A deficiency by ICDS beneficiaries. The ICDS scheme is being modified
      continuously to strengthen the programme.

PMID- 11243084
TI  - Prevalence of anaemia during pregnancy in district Burdwan, West Bengal.
AB  - A total of 653 women in third trimester of pregnancy were examined for the
      presence of anaemia in Kanksha and Ausgram II blocks of Burdwan. 80% of them were
      found anaemic (haemoglobin level < 11 gm%). 67% of the pregnant women took iron
      folates till varied periods. Iron deficiency was the commonest cause for the
      anaemia.

PMID- 11243085
TI  - National nutritional anaemia control programme in India.

PMID- 11243086
TI  - Study of impact of nutrition & health day strategy on the coverage rates of
      supplementary nutrition and health interventions among the ICDS beneficiaries in
      a rural block of Madhya Pradesh.
AB  - To study the trends of beneficiary coverage (pregnant and lactating women and
      children less than two years of age) for utilization of supplementary nutrition
      and health services in a rural block before and after the launch of a strategy to
      converge Health & Integrated Child Development Services (ICDS) on a single day
      christened "Nutrition and Health Day" (NHD). It is a before and after
      intervention design in rural ICDS block Amarwada in district Chhindwada. As a
      part of intervention, NHD were organised on which convergent services of Health &
      ICDS were made available to the beneficiaries. On the weekly NHDs, uncooked
      supplementary nutrition for the week was distributed to pregnant and lactating
      mothers and children under two. The Health worker visited the Anganwadi Centre
      (AWC) and immunized children and pregnant women, distributed IFA, Vitamin A and
      provided health and nutrition education. The study assessed the impact of these
      interventions on the coverage rates of the services. Study was conducted between
      May 97 and March 98. The routine monitoring reports of the ICDS and Health System
      of the state government were used as study tools. The study sample comprised of
      AWC beneficiaries in the project area. The total population of the block was
      89,476. Participation in the supplementary nutrition program (SNP) increased two
      to three folds in all categories of the target population. Immunization and
      Vitamin A coverage levels for children also showed an increase of about 3 and 5-8
      times from baseline status respectively in a year's time. Among pregnant women,
      Tetanus Toxoid (TT) and Iron and Folic Acid (IFA) utilization rates have also
      shown two and five fold increase respectively.

PMID- 11243087
TI  - Nutritional and immunisation status, weaning practices and socio-economic
      conditions of under five children in three villages of Bangladesh.
AB  - A total of 479 children aged 6-60 months (male/female, 240/239) were studies
      during 1991 to 1992. Weight for age, height for age (mean +/- SD) were 72 +/-
      11%, 90 +/- 7 and 87 +/- 10% of NCHS median respectively. According to Gomez
      classification, 96% of children had varying degrees of protein energy
      malnutrition (PEM) (28.4% mild, 58.2% moderate and 9.2% severe). According to
      Waterlow classification 84% were stunted(36% mild, 33% moderate and 15% severe)
      and 67% were wasted (47% mild, 18% moderate and 2% severe). Of all children 368
      (77%) received BCG and 439 (82%) received partial or full dose of DPT and Polio
      vaccines. Among children aged 13-60 months 75% received Measles vaccine. Weaning
      food was started at (mean +/- SD) 8 +/- 4 months. Low household income, parental
      illiteracy, small family size (< or = 6), early or late weaning and absence of
      BCG vaccination were significantly associated with severe PEM. Timely weaning,
      education and promotion of essential vaccination may reduce childhood
      malnutrition especially severe PEM.

PMID- 11243088
TI  - Body iodine status in school children and availability of iodised salt in
      Calcutta.
AB  - Success of Universal Salt Iodization (USI) programme depends on availability of
      iodised salt to consumers, which should be reflected in their body iodine status.
      From a monitoring study in Calcutta, it was found that all packed salts were
      iodised and most of them (98.1% at household level and 93.6% at retailers'
      outlets) had iodine at a level of > or = 15 ppm. Of the loose salts, 34.6% at
      household level and 19.9% at retailers' outlet had iodine level < 15 ppm. A few
      number (0.5% at household level and 1.0% at retailers' outlets) of salts had no
      iodine. To ascertain the impact of consumption of iodised salt iodine excreted in
      urine (UIE) was measured in school children of age between 8-12 years of south,
      east, west, north and central parts of Calcutta. 22.95% of male children and
      31.81% of female children had urinary iodine level less than 50 micrograms/l,
      which is cut off figure of public health concern. Children from poor slum areas
      were found to be at greater risk.

PMID- 11243089
TI  - Nutritional status of pavement dweller children of Calcutta City.
AB  - Pavement dwelling is likely to aggravate malnutrition among its residents due to
      extreme poverty, lack of dwelling and access to food and their exposure to
      polluted environment. Paucity of information about nutritional status of street
      children compared to that among urban slum dwellers, squatters or rural/tribal
      population is quite evident. The present study revealed the magnitude of Protein
      Energy Malnutrition (PEM) and few associated factors among a sample of 435
      underfives belonging to pavement dweller families and selected randomly from
      clusters of such families, from each of the five geographical sectors of Calcutta
      city. Overall prevalence of PEM was found almost similar (about 70%) to that
      among other 'urban poor' children viz. slum dwellers etc., but about 16% of them
      were found severely undernourished (Grade III & V of IAP classification of PEM).
      About 35% and 70% of street dweller children had wasting and stunting
      respectively. Severe PEM (Grade III & IV) was more prevalent among 12-23 months
      old, girl child, those belonged to illiterate parents and housewife mothers
      rather than wage earners. It also did increase with increase of birth rate of
      decrease of birth interval.

PMID- 11243090
TI  - Community participation in the field of health and nutrition.

PMID- 11243091
TI  - Behavior and activities in the central nervous system after activation of L-type
      calcium channels in mice.
AB  - The distribution of the immediate early gene c-fos expression in the mouse
      central nervous system after subcutaneous injection of Bay K 8644 was observed
      immunohistochemically. Half an hour after injection, c-fos protein (FOS) was
      expressed in the piriform cortex, sensorimotor cortex, caudate putamen, thalamic
      paraventricular nucleus and striate cortex, etc. Intense FOS immunoreactive (FOS
      ir) cells were seen during 2-4 h after injection. The results suggested that the
      distribution of FOS-ir cells after subcutaneous injection of Bay K 8644 was
      coincident with that of L-type calcium channels in the different areas of the
      CNS. After Bay K 8644 injection, mice appeared seizure-like behavior. The
      percentage of cells double-labelled by FOS and CaBP immunoreactivities in the
      observed regions was about 60.2-72.8% in CaBP-ir cells. It suggested that most
      CaBP-ir cells may have L-type calcium channels.

PMID- 11243092
TI  - Estrogen receptor-negative breast cancer cells transfected with estrogen receptor
      exhibit decreased tumour progression and sensitivity to growth inhibition by
      estrogen.
AB  - Breast cancer containing estrogen receptors (ER) are responsive to antiestrogen
      treatment and have a better prognosis compared with ER-negative tumors. The loss
      of estrogen receptors appears to be associated with a progression to less
      differentiated cells. We transfected the human ER into the ER-negative breast
      cancer cell line MDA-MB-231 cells. We found that expression of adequate ER is
      strong associated with the ability of human breast cancer cell growth inhibition
      and progression. Compared with nontransfected or mock-transfected cells, ER
      transfected cells exhibited growth slower, forming smaller colonies in soft agar
      and growth inhibited by estrogen and tamoxifen. Therefore reactivation or
      transfection of the estrogen receptor gene can be considered as therapeutic
      approaches to hormone-independent breast cancer.

PMID- 11243093
TI  - PCR amplification, molecular cloning, DNA sequence analysis and immuno/protection
      in BALB/C mice of the 33 kDa endoflagellar protein of L. interrorgans serovar
      lai.
AB  - A pair of oligonucleotide primers were designed to amplify the endoflagella gene
      of L. interrogans serovar lai. An approximately 840 bp fragment was generated
      with PCR and inserted into plasmid pUC8, after the fragment and pUC8 were
      digested respectively with BamHI and PstI. A recombinant plasmid (designated as
      pLF1) was obtained. SDS-PAGE analysis indicated that a 33 kDa was expressed in E.
      coli JM103 harboring pLF1 and the expression level of the protein was 11% of the
      total bacterial soluble proteins. Western blot analysis showed that the protein
      band could be recognized by the antiserum against the endoflegella (Axial
      filament) of Leptospira interrogans serover lai. Nucleotide sequence data showed
      an open reading frame encoding 282 aminoacids residues, corresponding to a
      protein of molecular weight 33.6 kDa. Comparison of the deduced endoflagellar
      subunit protein (flaB) amino acid sequence with flagellins from other bacteria
      revealed a high level of identity with the Treponema pallidum flaB proteins.
      Immunization/protection experiment was performed on the model of BALB/C mice and
      showed that there was higher survival rate in the group JM103-pLE1 than in the
      group JM103-pUC8.

PMID- 11243094
TI  - Two novel mutations in phenylalanine hydroxylase gene and in vitro expression
      analysis on mutation Arg252Gln.
AB  - We report novel mutations in exon 7 of human phenylalanine hydroxylase (PAH) gene
      of phenylketonuria (PKU) in southern Chinese, analysed by using PCR-DGGE
      (denaturing gradient gel electrophoresis), solid phase DNA sequencing and in
      vitro expression. One of the 2 novel mutations, IVS6nt-1, is an intron-exon
      junctional mutation which results a splicing defect in mRNA. Arg252Gln is another
      novel mutation with residual PAH activity only 24% compared to wild type in in
      vitro mutagenesis and expression in Cos-1 cell. Other 3 known mutations and
      polymorphism including Arg241Cys, Arg243Gln and Val245Val (GTG to GTA) together
      with these novel mutations composed the mutational profile of exon 7 in the PAH
      gene of PKUs in this populations.

PMID- 11243095
TI  - A comparative study of gut suture, human amnion collagen, bovine skin collagen
      and Vicryl suture implants in rats.
AB  - This study compares the persistence and histological characteristics of gut
      suture with those of human amnion collagen, bovine collagen, and Vicryl suture
      implants in rats. Gut suture and human amnion collagen more resembled living
      tissue than did bovine collagen and were characterized by their cellularity and
      the presence of numerous capillaries. The Vicryl suture implants were quickly
      absorbed. Picrosirius polarization revealed the synthesis of host collagen by rat
      fibroblasts which immigrated into the gut suture and human amnion collagen
      implants. The authors suggest the potential of gut suture as a soft tissue
      substitute to improve linear skin contour deficits.

PMID- 11243096
TI  - Research on the estimate of safety and toxicity of p-nitrophenol sodium with a
      physiologically based pharmacokinetics model.
AB  - The safety and toxicity of chemicals given first to animals and finally to humans
      are generally estimated with a method of safe coefficient, which is
      scientifically a way lack of grounds. To make a change of the old method, we
      designed a Physiologically-Based Pharmacokinetics Model for the estimate of
      safety and toxicity of chemicals. As an example, p-nitrophenol sodium (PNP-Na) is
      used in the research work. Studies of the PNP-Na pharmacokinetics in bodies of
      rat as well as humans are made, and possibilities of making use of the Model in
      the estimate of safety and toxicity of chemicals are discussed.

PMID- 11243097
TI  - Expression of HBV Pre S1 peptide in E. coli and product characterization.
AB  - HBV Pre S1 sequence is supposed to play an important role in the infection of
      HBV. Presence of Pre S1/anti-Pre S1 in serum has valuable clinical implications.
      In order to improve the study of Pre S1, Pre S1 sequence was overexpressed in E.
      coli as a fusion protein with MBP (Maltose-binding protein), and anti-Pre S1
      antiserum was elicited in rabbits by Pre S1-MBP purified by affinity
      chromatography. The recombinant plasmid constructed from pMAL-cRI expressed the
      106aa Pre S1 sequence at the C terminal of MBP by tac promoter. The resulting
      protein is about 54 kD in size. Western-blot analysis confirmed its reactivity
      with antiserum derived from synthetic Pre S1 peptide and serum from patients with
      acute hepatitis B (AHB). ELISA showed that Pre S1-MBP and Dane particles purified
      from AHB patient's serum reacted with antiserum against synthetic Pre S1 peptide,
      and this reaction was specifically inhibited by synthetic Pre S1 peptide. ELISA
      also demonstrated that antiserum against Pre S1-MBP reacted with synthetic Pre S1
      peptide, but not with synthetic HCV peptide or HEV peptide.

PMID- 11243099
TI  - Analysis of the antigen-antibody specificity in the semen of patients with
      Neisseria gonorrhoeae.
AB  - This study was done to define the human genital immune response to infection with
      Neisseria gonorrhoeae. The semen specimens were obtained from 15 patients with
      uncomplicated gonococcal infection in the acute and convalescent phases and 15
      men with uninfected control. After precipitated with amoniasulfate, the semen was
      tested against the outer membrane protein of gonococcal isolates from the same
      patients to examine antigen-antibody interactions by use of the western blot
      technique. The antibodies in the semen reacted with more gonococcal antigens in
      the acute phase than in the convalescent phase. IgA in the semen reacted with
      more antigens than did IgG in the same specimens. The predominant reacted
      antigens were protein I, protein II, 46-48, kD, 14-16 kD and 88-90 kD protein.

PMID- 11243098
TI  - Expression of TNF alpha, IL-1 beta, IL-6 mRNA, release of TNF alpha in vital
      organs and their relationship with endotoxin translocation following hemorrhagic
      shock.
AB  - This study was designed to systematically investigate expression of TNF alpha, IL
      1 beta, Il-6 mRNA in the liver, lungs and kidneys, release of TNF alpha in the
      above tissues, their relationship with hepatic, pulmonary and renal dysfunction,
      and distribution of endogenous endotoxin in tissues after hemorrhagic shock in
      mice and rats, with reverse-transcription-polymerase chain reaction, ELISA, etc,
      to elucidate the kinetics of expression and release of major cytokines in vital
      organs, their role and mechanism of production in shock. The results were: 1.
      expression of TNF alpha, IL-1 beta, IL-6 mRNA in vital organs successively
      increased after hemorrhagic shock and resuscitation, and TNF alpha expression was
      the first to appear followed by IL-1 beta. Though expression of IL-6 mRNA
      appeared late, it persisted longer; 2. TNF alpha levels in the liver, lungs and
      kidneys were all elevated but to different degrees after shock and resuscitation.
      At 3 hours after resuscitation, TNF alpha levels in the three above tissues were
      still significantly high, while plasma TNF alpha levels were already decreased to
      control levels; 3. hepatic, pulmonary and renal functions were damaged to
      different degrees after hemorrhagic shock, with hepatic dysfunction being the
      most severe; 4. endotoxin levels in the liver, lungs and kidneys were markedly
      increased after shock and resuscitation, and paralleled the expression of
      cytokine genes. In addition, there was significant correlation between changes in
      endotoxin level in tissues and TNF alpha release in tissues during early shock.
      It is suggested that expression and release of cytokines in vital organs might
      play an important role in local organ damage after hemorrhagic shock, and
      production of cytokines is related to endotoxin translocation.

PMID- 11243100
TI  - Characteristic of facial muscle and efferent nerve on physiology and anatomy.
AB  - OBJECTIVE: To study the specialty of orbicularis oculi muscles, nerves and oris
      muscles, nerves and mechanism of difference of facial muscular injury in facial
      paralysis deeply. METHODS: The conductive velocity of the efferent nerves of
      orbicularis oculi and oris muscles of the health human beings and guinea pigs is
      measured with electromyogram (EMG) apparatus. RESULTS: The conductive velocity of
      orbicularis oculi nerve is quicker and oris muscles are controlled by facial
      nerves on both sides. Measuring the threshold of Strength-Duration (S-D) curves
      of the motor point of orbicularis oculi and oris muscles shows the threshold of
      the former is lower. Measuring the diameter of orbicularis oculi and oris nerve
      fibers on the guinea pigs and rabbits shows the diameter of orbicularis oculi
      nerve fiber is bigger. The area of secondary synapse space of orbicularis oculi
      motor end plate is larger than that of oris under scanning electron microscope.
      CONCLUSIONS: Orbicularis oculi muscles, orbicularis oculi nerves and oris
      muscles, oris nerves all have their own characteristic on physiology and anatomy.
      It elucidated the mechanism that orbicularis oculi muscle is easy to be injured.

PMID- 11243101
TI  - Measurements of intraocular pressure throughout the pregnancy in Pakistani women.
AB  - BACKGROUND: Decrease in intraocular pressure (IOP) during pregnancy has been
      reported by previous studies, but amount of decrease varies from study to study.
      Moreover, previous studies have concentrated on the last trimester of pregnancy
      or one reading per trimester. IOP changes throughout the pregnancy have never
      been described. Therefore, the present study was planned to determine IOP
      throughout the pregnancy, after placing control on IOP affecting factors.
      SUBJECTS AND METHODS: Thirty-six pregnant and same numbers of non-pregnant women
      of the same age group were studied. IOP measurements were taken at four week
      intervals throughout the pregnancy, with the Goldmann applanation tonometer.
      RESULTS: As compared to control subjects, up to 8th week, IOP remained the same.
      At 12th week, it becomes significantly lower. The IOP differences between first
      and second (P < 0.05), and second and third (P < 0.001) trimesters of pregnancy
      were significant. In every subject, IOP decreased during pregnancy. However,
      there were variations among individuals in the extent of IOP decrease.
      CONCLUSIONS: With advancing pregnancy, intraocular pressure decreases. Knowledge
      of the normal level of intraocular pressure in various stages of pregnancy may
      help glaucoma screeners.

PMID- 11243102
TI  - Potassium channels on cardiomyocytes of selenium iodine deficiency rats and
      iodine deficiency rats.
AB  - Using diet control method to feed the weaning male Wistar rats with selenium and
      iodine deficiency Keshan endemic area food for 8 weeks to set up animal model.
      Singal channel recording in cell attached model was used to measure cardiac cell
      membrane potassium channel conductances, which coincide with the cardiac cell
      membrane potassium channel conductances in normal Wistar rats. The potassium
      channel conductance on selenium and iodine deficiency rat cardiac cell membrane
      is showing current-voltage increasing lineally in the range of clamping voltage 0
      +/- 30 mV with channel conductance of 43.4 pS. The channel current does not
      increase depending on the clamping voltage that is showing the rectifying
      characteristic and the channel current amplitude can be augmented by added KIOa 5
      mmol/L in bath solution. A kind of inward rectifying potassium channel activity
      was recorded, but this channel activity disappeared after lasting 6-10 minutes
      only. Then an inward rectifying potassium channel with the conductance of 14.2 pS
      was activated by KIOa 5 mmol/L introduced to bath solution. Both conductances are
      less than that of normal Wistar rats.

PMID- 11243103
TI  - Molecular alteration of alpha-induced transformed Syrian hamster embryo cells.
AB  - Syrian hamster embryo (SHE) cells are irradiated by alpha particles emitted from
      Plutonium-238 in vitro. Transfection frequencies of donor DNA derived from
      passaged cells, including monocloned cells from 20th passage cells, after
      irradiation are parallel with their tumorigenicity of donor cells. After
      transformation, expressions of H-ras and c-myc genes are in the state of
      activation, which might be resulted from occurrence of mutation in H-ras gene and
      hypomethylation of c-myc gene respectively, even though no alteration was
      observed on their restriction fragment length polymorphisms (RELP) patterns of
      both genes. On the other hand, expression of p53 gene is also found to be in the
      state of activation in transformant, but no heavy staining of p53 protein
      appeared in the transformant-derived tumor with p53 specific McAb HD 200. This
      might be result from the partial deletion of p53 cDNA in transformant by reverse
      transcriptional polymerase chain reaction (RT-PCR). These results imply that
      activation of H-ras and c-myc genes coupled with inactivation of p53 tumor
      suppressor gene play important role in alpha particle-induced cell
      transformation.

PMID- 11243104
TI  - The correlations of clinicopathologic features, hormone receptor level with the
      prognosis of breast cancer: report of 308 cases in elderly women.
AB  - OBJECTIVE: This study analyses the clinicopathologic features and hormone
      receptor level of breast cancer in aged patients (> or = 60 years) and explores
      the related factors of the prognosis. METHODS: For all patients, the clinical
      data and pathologic data were reviewed retrospectively. Follow-up data were
      available. Of the 308 cases, tumor specimens in 130 patients were subjected to
      hormone receptor analysis by a dextran-coated charcoal technique. RESULTS: Of the
      308 cases, 82 cases were in stage I, 147 cases in stage II, 66 cases in stage
      III, and 13 cases in stage IV. Metastatic rate (axillary lymph nodes) was 35.7%.
      The overall postoperative 5- and 10-year survival rates were 70.8% and 50.5%,
      respectively. Estrogen receptor and progesterone receptor positive rates were
      66.9% and 40.0%, respectively. The survival rate was decreased with the
      increasing grade of TNM (P < 0.01). The mortality rate of the breast cancer was
      related to the clinical stage and the hormone receptor level (P < 0.05).
      CONCLUSIONS: There was a relatively good prognosis in this series. The size of
      tumor, number of metastatic nodes and hormone receptor level were related to the
      prognosis.

PMID- 11243105
TI  - [Strengthen the basic and clinical study of hematopoietic modulation].

PMID- 11243106
TI  - [Analysis of surface markers of long-term cultured human umbilical cord blood
      hemopoietic cells].
AB  - OBJECTIVE: To explore the optimal time for in vitro expansion and transplantation
      of umbilical cord blood hemopoietic cells. METHODS: Hemopoietic cells from human
      umbilical cord blood were cultured with SCF, rIL-3, rIL-6 and rIL-1 beta in a
      long term culture system and changes of cellular surface markers were observed.
      RESULTS: CD3+ and CD20+ lymphocytes increased at the 7th day, and gradually
      decreased to the lowest level after the 14th day. CD34 positive cells increased
      after the 7th day, and reached the highest level at the 14th day, then decreased
      gradually but maintained at a higher level than that at the 7th day. CD33
      positive cells increased at the 7th day, and reached the highest level from the
      14th to the 21st day, then decreased after the 28th day. CD42b positive cells
      began to increase at the 21st day, reached the peak at the 28th day, and still
      maintained higher level at the 35th day. HLA-DR positive cells increased from the
      14th to the 21st day. CONCLUSION: The culture system containing the four growth
      factors is able to expand hemopoietic cells from human umbilical cord blood and
      keeps them intact. From the 14th to the 21st day, the number of hemopoietic cells
      reached the highest level, and is suitable for transplantation.

PMID- 11243107
TI  - [Studies on the committed differentiation of CD34+ hematopoietic progenitor
      cells].
AB  - OBJECTIVE: To elucidate the capacity of different hematopoietic growth factors
      (HGFs) combinations for inducing CD34+ cells to proliferate and differentiate
      committedly to granulocytes, erythrocytes, megakaryocytes and dendritic cells
      (DC). METHODS: CD34+ cells were isolated from umbilical cord blood by using a
      high-gradient magnetic cell sorting system (MACS), and expanded with HGFs in a
      liquid culture system. Colony forming cells and antigen expression were studied
      by colony forming assays and FACS. RESULTS: Different combinations of HGFs,
      including SCF, IL-3, IL-6, GM-CSF, Epo and Tpo increased BFU-E, CFU-GM, CFU-MK
      and CD41a+ cells by 14.97 +/- 2.89 fold, 14.46 +/- 3.19 fold, 34.67 +/- 4.62 fold
      and 17.29 +/- 2.34 fold, respectively. Combination of HGFs allowed generation of
      a large number of DCs. Cultures of CD34+ cells with the combination of FLT-3
      ligand + GM-CSF + IL-4 + TNF-alpha yielded 24.28% +/- 2.14% CD1a+ cells, while
      the control cultures did not. CONCLUSION: It is possible to induce CD34+ cells to
      proliferate and differentiate committedly to different lineage of hematopoietic
      cells and DC.

PMID- 11243108
TI  - [Therapeutic effects of combined suicide gene and cytokine gene therapy on
      erythroleukemia-bearing mice].
AB  - OBJECTIVE: To explore the antitumor effect of combined transfer of suicide gene
      and GM-CSF gene in erythroleukemia-bearing mice. METHODS: Adenovirus harboring E.
      coli. cytosine deaminase (CD) gene (Ad-CD) and/or GM-CSF gene (Ad-GM-CSF) were
      used for the treatment of erythroleukemia-bearing mice. The mice were inoculated
      with FBL-3 erythroleukemia cells subcutaneously and 3 days later received Ad-CD
      followed by 5-fluorocytosine (5FC) treatment with or without Ad-GM-CSF. RESULTS:
      The mice received Ad-CD/5FC and Ad-GM-CSF developed tumors more slowly and
      survived much longer than those received Ad-CD/5FC alone, Ad-GM-CSF alone,
      control virus Ad-LacZ/5FC or PBS. Combined transfer of CD gene and GM-CSF gene
      induced a higher specific CTL activity than control therapies did. Pathological
      examination illustrated that there were tumor necrosis and massive lymphocyte
      infiltration in the mice after the combined therapy. CONCLUSION: Combined
      transfer of suicide gene and cytokine gene could synergistically inhibit the
      growth of erythroleukemia cells in the mice and induce tumor specific immunity of
      the host.

PMID- 11243109
TI  - [Studies on the in vivo induction of differentiation of the erythroleukemia cells
      by the antigen-pulsed dendritic cells modified with GM-CSF gene].
AB  - OBJECTIVE: To investigate the function and mechanism of dendritic cells in the
      immunotherapy for tumors. METHODS: C57BL/6 mice inoculated with erythroleukemia
      cells were used as models. Inhibition or induction of tumor cell differentiation
      was observed by fluorescence-activated cell sorting (FACS) and transmission
      electron microscopy. RESULTS: After pulsed with FBL-3 antigen, the GM-CSF gene
      transfected dendritic cells inhibited the proliferation of the tumor cells. The
      expression of CD14 was increased and the expressions of MHC-II, B7-1, B7-2 and
      VCAM-1 were also up-regulated. Erythroleukemia cells in different differentiating
      stages were observed in tumor tissues. Under transmission electron microscope,
      the volumes of FBL-3 cells were reduced, the amount of lysosome and hetero
      chromatin became plentiful, the nucleocytoplasmic ratio was decreased, and
      apoptosis was revealed in erythroleukemia cells. The CD8+ cells were increased in
      peripheral blood and tumor tissues. CONCLUSION: The antigen-pulsed dendritic
      cells modified with GM-CSF gene could induce in vivo the erythroleukemia cells to
      differentiate into monocytes.

PMID- 11243110
TI  - [The effect of cytokines on the activation of T cells induced by B7-1-transfected
      leukemia cells].
AB  - OBJECTIVE: To observe the effects of IL-12, IFN-gamma, IL-10 on the B7-1
      expression of B7-1 transfected leukemia cells (K562 and HL-60) and on the IL-2
      and IFN-gamma expression and production in the peripheral blood mononuclear
      cells(PBMC) induced by B7-1 transfected K562 and HL-60 cells. METHODS: RT-PCR and
      ELISA techniques were used to assay the expression and production of IFN-gamma
      and IL-2. RESULTS: IFN-gamma and IL-12 increased the expressions of B7-1, IL-2
      and IFN-gamma, but IL-10 inhibited all the expressions. CONCLUSION: IFN-gamma, IL
      10 and IL-12 affected the expression and production of IFN-gamma and IL-2
      possibly by affecting the B7-1 expression.

PMID- 11243111
TI  - [Both myeloma cells and bone marrow stromal cells are involved in the
      overproduction of interleukin 6 in multiple myeloma].
AB  - OBJECTIVE: To investigate the mechanism of interleukin 6 (IL-6) overexpression in
      multiple myeloma(MM). METHODS: Human myeloma cells(KM3) and bone marrow stromal
      cells(BMSCs) were fixed by paraformaldehyde. KM3 cells and BMSCs (fixed and non
      fixed) were co-cultured in 10%FCS-RPMI1640. IL-6 activity in the supernatant was
      determined by B9 cell proliferation test. RESULTS: Both non-fixed myeloma cells
      and BMSCs could automatically secret IL-6, while the fixed cells did not. Co
      cultures of fixed one with non-fixed the other of either kind of the cells could
      significantly increase the IL-6 activity in the supernatants. The promoting
      effect on IL-6 production was greater in BMSCs from MM patients than that in
      BMSCs from normal controls. CONCLUSION: There exists dual mechanism of IL-6
      overproduction in MM, i.e. both autocrine and paracrine of IL-6 are involved in
      the pathogenesis of MM.

PMID- 11243112
TI  - [Treatment of malignant hematological diseases with autologous peripheral blood
      stem cell transplantation].
AB  - OBJECTIVE: To observe the effectiveness of autologous peripheral blood stem cell
      transplantation(ABSCT) in the treatment of malignant hematologic diseases.
      METHODS: Thirteen ABSCT and 15 autologous peripheral blood stem cells(ABSC)
      combining autologous bone marrow transplantation (ABMT) were performed for
      hematological malignancy patients. RESULTS: In polyactin A mobilization group,
      the mononuclear cells(MNC) collected in each case were 3.58 +/- 2.12 x 10(8)/kg,
      and in G-CSF mobilization group 6.68 +/- 5.31 x 10(8)/kg. Twenty-one of the 28
      transplanted cases achieved continuous complete remission(CCR). The medium CCR
      duration was 18(5-58) month. The 3 year disease-free survival rate was 68.7% and
      relapse rate was 22.3%. CONCLUSION: After ABSCT or ABSC combining ABMT, there
      were earlier hematopoietic reconstitution and fewer complications than that after
      ABMT.

PMID- 11243113
TI  - [Application of IHW2 purged bone marrow to autologous bone marrow transplantation
      in the treatment of acute myeloid leukemia].
AB  - OBJECTIVE: To observe the clinical effectiveness of IHW2 purged autologous bone
      marrow transplantation (ABMT) in the treatment of AML patients. METHODS: Large
      volume of bone marrow was purged in vitro by IHW2 and then reinfused to patients
      for ABMT. RESULTS: All of the three patients transplanted with IHW2 purged
      autologous bone marrow successfully reconstituted hemopoiesis. Two patients got
      continuous complete remission for 36+ and 34+ months, respectively. The karyotype
      of one of the two patient was 46,XY,del(16)(q22) before ABMT and changed to 46,XY
      in 2 months after transplantation. The third patient relapsed after ABMT 19
      months. CONCLUSION: The preliminary study suggests that IHW2 may have certain
      purging effect on leukemic cells and is safe for clinical application.

PMID- 11243115
TI  - [Progress in the study of autologous hematopoietic stem cell transplantation
      therapy of multiple myeloma].

PMID- 11243114
TI  - [Study on expression of Evi1 and MDS1-Evi1 genes in myelodysplastic syndromes].
AB  - OBJECTIVE: To investigate expression of Evi1 and MDS1-Evi1 genes in
      myelodysplastic syndromes (MDS) and its role in pathogenesis of MDS. METHODS:
      Expression of Evi1 and MDS1-Evi1 genes was examined in 31 MDS, 11 post MDS acute
      myeloid leukemia (post MDS AML) and 34 de novo AML patients by a semi
      quantitative RT-PCR. RESULTS: Evi1 expression was not detected in 8 normal
      controls, but low MDS1-Evi1 expression levels (MDS1-Evi1/GAPDH < 0.1) detected in
      3 of the 8 controls. Evi1 mRNA was expressed in 1 of 8 RA, 8 of 13 RAEB and 6 of
      9 RAEB-t patients, and the percentage of Evi1 expression in RAEB(t) patients was
      higher than that in RA(P < 0.05). MDS1-Evi1 expression was detected in 5 of 8 RA,
      9 of 13 RAEB and 5 of 9 RAEB-t patients, and MDS1-Evi1 expression levels (MDS1
      Evi1/GAPDH > 0.1) in the patients were markedly higher than those in the
      controls. Evi1 expression was gradually increased in 4 of 5 RAEB-t patients with
      transformation from MDS to AML. The percentages of Evi-1 and MDS1-Evi1 expression
      in post MDS AML patients were higher than those in de novo AML (P < 0.01 and P <
      0.05, respectively). The numbers of colony formation of progenitor cells in Evi1
      and MDS1-Evi1-positive MDS patients were decreased as compared with Evi1 and MDS1
      Evi1-negative patients. CONCLUSION: Abnormal expression of Evi1 and
      overexpression of MDS1-Evi1 might play a certain role in the pathogenesis or
      progression of MDS and post MDS AML.

PMID- 11243116
TI  - [Effect of antisense oligodeoxynucleotide (ASODN) to PML-RAR alpha fusion gene on
      acute promyelocytic leukemia cell line NB4].
AB  - OBJECTIVE: To study the effect of PML-RAR alpha expression on the proliferation
      and differentiation of NB4 cells, and explore the role of PML-RAR alpha fusion
      gene in the pathogenesis of acute promyelocytic leukemia (APL). METHODS: ASODN
      mediated inactivation of PML-RAR alpha mRNA was measured by RT-PCR. The
      proliferation and differentiation of NB4 cells were determined by proliferation
      curve, morphology, membrane CD antigen and NBT test. NB4 cell cycle was analyzed
      by FACS. RESULTS: The inactivation of PML-RAR alpha mRNA by ASODN decreased the
      percentage of S phase cells (from 56% to 37%), inhibited the NB4 cell
      proliferation and induced NB4 cells to differentiate to morphologically and
      functionally mature granulocytes. CONCLUSION: PML-RAR alpha gene, as a molecular
      marker of APL, is possibly responsible for genesis of APL.

PMID- 11243117
TI  - [Experimental study of anti-tumor immunity induced by B7 vaccine of a highly
      malignant murine leukemic T cell line (L615)].
AB  - OBJECTIVE: To assess the potential of B7-1 vaccine in inducing immunity to
      leukemic cells. METHODS: B7-1 gene was introduced into L615 cells and then the
      positive clone (L615-B7) highly expressing B7-1 was selected. Tumorigenic and
      immunoprotective activities of L615-B7 cells were studied in vivo. T cell
      functions of cytotoxicity, proliferation and growth factor secretion were
      detected in vitro.

PMID- 11243118
TI  - [Protein tyrosine kinase (PTK) activities during the induction of apoptosis by
      arsenic trioxide (As2O3)].
AB  - OBJECTIVE: To explore the mechanism of arsenic trioxide (As2O3) induced apoptosis
      in K562 cell line. METHODS: Immunoprecipitation was used to obtain BCR/ABL and
      ABL proteins. The activities of PTK and tyrosine phosphorylation were measured by
      biochemical method and Western blot, respectively. RESULTS: As2O3 reduced the PTK
      activities of cytosol and membrane proteins and BCR/ABL and ABL proteins. The
      tyrosine phosphorylation of 180,000 and 125,000 proteins declined. CONCLUSION:
      As2O3 may interfere the signal transduction of BCR/ABL protein by reducing its
      PTK activity and induce K562 cell apoptosis.

PMID- 11243119
TI  - [Retinoic acid inducing Fas expression in HL-60 cells].
AB  - OBJECTIVE: To investigate the effect of all-trans retinoic acid (ATRA) and 9-cis
      retinoic acid (9-cis RA) on the expression of Fas and the sensitivity to anti-Fas
      induced apoptosis in HL-60 cells. METHODS: Fas expression was detected by flow
      cytometry. Anti-Fas induced apoptosis (AFIA) was determined by morphological
      features, DNA fragment electrophoresis, and flow cytometric cell cycle analysis.
      RESULTS: Fas antigen was weakly expressed on HL-60 cells. After incubation of HL
      60 cells with 10(-6) mol/L ATRA or 9-cis RA for 4 days, both the Fas expression
      and AFIA were significantly enhanced. 9-cis RA was more potent than ATRA in
      increasing the sensitivity to AFIA. CONCLUSION: RA might upregulate Fas
      expression. Further elucidation of its molecular mechanisms might provide a
      rationale for new therapeutic strategies of malignant diseases.

PMID- 11243120
TI  - [Induction of apoptosis and differentiation in human leukemia cell line HL-60 by
      synthetic retinoid Ro13-7410].
AB  - OBJECTIVE: To investigate the effect of the synthetic retinoid Ro13-7410 on HL-60
      cells. METHODS: Trypan blue exclusion was used to determine viability. Apoptosis
      was assessed by cell morphology and PCD-assay-kit. Differentiation was assessed
      by morphology and NBT reduction. RESULTS: Incubation of the HL-60 cells with 10(
      6)-10(-8) mol/L Ro14-7410 resulted in the suppression of cell growth, the
      induction of cell apoptosis and differentiation. CONCLUSION: Ro13-7410 suppressed
      HL-60 cell growth mainly via induction of apoptosis.

PMID- 11243121
TI  - [Fas mediated apoptosis inhibited by human bcl-2 gene in lymphoma cell line
      Jurkat].
AB  - OBJECTIVE: To understand the mechanism of bcl-2 gene in escaping the immune
      surveillance in the development of lymphoma. METHODS: A recombinant retroviral
      vector pLXSN-bcl-2 was constructed by cloning bcl-2 cDNA into the replication
      defective retroviral vector pLXSN, and transferred to packaging cell line PA317
      by electroporation. The G418 resistant colonies were selected, and the
      supernatants of the colony cultures were used to infect the human lymphoma cell
      line Jurkat. Cells in G418 resistant Jurkat colonies were characterized by
      immunohistochemistry. Anti-Fas monoclonal antibody (McAb) was applied to Jurkat
      cells for inducing apoptosis which mimicked the cytotoxic activity of T
      lymphocyte. RESULTS: Expression of bcl-2 in pLXSN-bcl-2 transfected Jurkat cell
      (Jurkat-bcl-2) increased, while there was no change of Fas gene expression.
      Apoptosis was blocked in Jurkat-bcl-2 by anti-Fas McAb treatment. CONCLUSION:
      Overexpression of bcl-2 in lymphoma cell line could inhibit cell apoptosis
      induced by anti Fas McAb, suggesting that overexpression of bcl-2 is one of the
      mechanisms in escaping immune surveillance in the development of lymphoma.

PMID- 11243122
TI  - [A study of the GSH contents, GST activity and the expression of GST isoenzyme
      and MRP in drug-resistant leukemic cell lines].
AB  - OBJECTIVE: To understand the non-mdr1 mechanism in multidrug-resistant leukemic
      cell lines. METHODS: GSH contents and GST activity were measured by biochemical
      methods, the expression of GST isoenzyme alpha, pi, mu and MRP mRNAs were
      examined by Northern blot, and the expression of GST alpha, pi, mu proteins were
      examined by Western blot in sensitive HL-60, K562 and resistant K562/H20, HL
      60/Adr, K562/VCR leukemic cell lines, respectively. RESULTS: Compared with
      K562/S, GSH contents and GST activities were increased in K562/H20 and K562/VCR,
      and GST alpha, pi or GST mu, pi were overexpressed in K562/H20 or K562/VCR, while
      there was no difference of GSH contents, GST activities or GST isoenzyme
      expressions between HL-60/Adr and HL-60/S. The increased expressions of MRP mRNA
      were revealed in the three resistant cell lines. CONCLUSION: GSH, GST and MRP
      involved in the drug resistance of K562/H20 and K562/VCR, while only MRP
      associated with drug resistance of HL-60/Adr.

PMID- 11243123
TI  - [Construction of the internal standard RNA and DNA templates for MRP gene
      quantitative RT-PCR analysis].
AB  - OBJECTIVE: To construct the internal standard RNA and DNA templates for
      quantitative reverse transcription-polymerase chain reaction (RT-PCR) and
      quantitatively measure the mRNA expression of MRP gene. METHODS AND RESULTS: A
      292 bp fragment was amplified by PCR from plasmid pRC/RSV-MRP containing full
      length MRP cDNA and inserted into the Sma I site of PUC19 vector, constructing a
      recombinant plasmid-pUMRP292. A 238 bp HGV fragment was amplified by PCR from
      plasmid pUHGV and inserted into the Cla I site of pUMRP292, constructing a new
      recombinant plasmid-pUMRP 292/HGV as the internal DNA competitive template for
      quantitative PCR of MRP. A 530 fragment containing the 292 bp of MRP and the 238
      bp of HGV was cut down by EcoR I and Xba I pUMRP292/HGV and cloned into the
      transcriptional vector pSP72 by the same enzyme sites, constructing a recombinant
      plasmid-pSMRP292/HGV, and then pSMRP292/HGV was cleaved with EcoR V and
      transcripted in vitro by SP6 RNA polymerase, obtaining a 530 bp mutant MRP-RNA
      positive strand as the internal RNA competitive template for quantitative RT-PCR.
      CONCLUSION: The established quantitative RT-PCR assay is simple, rapid and
      sensitive, and the DNA competitive template is more simple, economic and reliable
      than the RNA one.

PMID- 11243124
TI  - [Role of fibonectin in hematopoiesis].

PMID- 11243125
TI  - [Study of the multidrug gene transfer to bone narrow hematopoietic cells and
      clinical uses].

PMID- 11243126
TI  - [Classification of acute and chronic aplastic anemia].

PMID- 11243127
TI  - [Clinical study of aplastic anemia].

PMID- 11243129
TI  - [Study on the improvement of bone marrow microenvironment by ligustrazine in
      immune-induced aplastic anemia mice].
AB  - OBJECTIVE: To explore the effects of ligustrazine on bone marrow microenvironment
      and its mechanism in aplastic anemia (AA). METHODS: Each immune-induced AA mouse
      was gastric fed by 4 mg ligustrazine twice a day. On the 10th day, the ulnar bone
      marrow partial pressure of oxygen (PbO2) was determined in vivo by a PO2 sensory
      needle. Then the histological features, fibroblastic colony forming unit (CFU-F)
      yields and the adhesive function of stromal cells of the bone marrow were assayed
      in vitro. RESULTS: The PbO2 in ligustrazine-treated group was 10.32 +/- 1.27 kPa,
      while in AA group was 4.32 +/- 2.86 kPa (P < 0.001). In AA group, the
      microvessels were expanded, broken and being stasis. The percentage of
      hematopoietic tissue volume was 24.9% +/- 9.6% and the CFU-F yields was 12.5 +/-
      7.3/2 x 10(6) BMNC. The microvessels in ligustrazine group were more clear and
      intact, not being broken and had no stasis. The percentage of hematopoietic
      tissue volume was 52.8% +/- 15.6% and the CFU-F yields was 31.5 +/- 10.6/2 x
      10(6) BMNC. In ligustrazine group, the adhesive function of stromal cell layer
      cultured with bone marrow nucleated cells from normal mice was 72.7% +/- 7.8%,
      which was not different from that in normal group (73.4% +/- 3.4%), but much
      higher than that in AA group (56.2% +/- 9.8%, P < 0.01). CONCLUSION: Ligustrazine
      can promote the rehabilitation of bone marrow microvessels in AA mice, increasing
      the oxygen supply for bone marrow microenvironment, promoting the growth of
      stromal cells and strengthening their adhesive function. Ligustrazine enbances
      the bone marrow hematopoietic cells proliferation by improving their
      microenvironment.

PMID- 11243128
TI  - [Treatment of chronic aplastic anemia with triolandren and cyclosporin A].
AB  - OBJECTIVE: To explore more effective regimen for chronic aplastic anemia (CAA).
      METHODS: Forty-five cases of CAA were treated with triolandren (TLD) (15 cases)
      or TLD and cyclosporin A (CsA) (30 cases). RESULTS: The response rate of TLD-CsA
      group (83.3%) was higher than that of TLD group (60.0%), furthermore, the
      recovery of bone marrow colony-forming cell (CFC) number of the responding
      patients was more complete and rapid in TLD-CsA group than in TLD group. Bone
      marrow CFC number had no significant change of all nonresponding patients in both
      groups. CONCLUSION: The response rate of TLD-CsA was higher than that of TLD
      alone, and the recovery of bone marrow CFC number of the responding patients was
      more complete and rapid in TLD-CsA group.

PMID- 11243130
TI  - [Study on the cellular immune function and cytokines in aplastic anemia
      patients].
AB  - OBJECTIVE: To evaluate the effects of cellular immune function and cytokines on
      the pathogenesis of aplastic anemia (AA) and its clinical significance. METHODS:
      T lymphocyte subsets and HLA-DR antigen expression in the peripheral blood cells
      were assayed, and the levels of G-CSF, IL-6, TNF alpha, IFN alpha and IL-8 in the
      PBMNC culture supernatants were determined in 38 AA patients and 20 normal
      control with APAAP and ELISA methods. RESULTS: CD4+ cells, CD4+/CD8+ cells and G
      CSF level were lower, and CD8+ cells, HLA-DR+ cells and IL-6, TNF alpha, IFN
      alpha and IL-8 levels were higher in AA patients than in normal controls. The
      level of G-CSF was positively correlated with CD4+ cells and CD4+/CD8+ cells and
      negatively with IFN alpha level. IL-6 level was negatively correlated with WBC
      count and CD4+ cells. TNF alpha level was positively correlated with CD8+ cells
      and negatively with CD4+/CD8+ cells. IL-8 level was positively correlated with
      CD8+ cells and HLA-DR+ cells. CONCLUSION: The cellular immune dysfunction and
      cytokine aberration participate in the pathogenesis of AA.

PMID- 11243131
TI  - [Detection of interleukin-8 level in peripheral blood of patients with aplastic
      anemia].
AB  - OBJECTIVE: To investigate the role of interleukin-8 in the pathogenesis of
      aplastic anemia (AA) and its correlation with clinical status. METHODS: Serum
      level of IL-8 in 24 AA patients and 20 normal controls was measured by sandwich
      enzyme linked immunosorbent assay(ELISA). RESULTS: The levels of IL-8 were
      increased significantly(P < 0.05) in AA patients than in normal controls, and the
      IL-8 levels in severe AA group were much higher than those in chronic AA group (P
      < 0.05). Serum IL-8 in AA patients with infection were elevated significantly(P <
      0.005). CONCLUSION: IL-8 may have a potential role in the pathogenesis of AA and
      determination of serum IL-8 may be helpful for evaluation of severity and
      infectious complication of AA.

PMID- 11243132
TI  - [Serum level of granulocyte colony stimulating factor in severe aplastic anemia
      patients].
AB  - OBJECTIVE: To investigate the relationship between serum level of granulocyte
      colony stimulating factor (G-CSF) and clinical status, treatment outcome and
      prognosis in severe aplastic anemia (SAA-I) patients. METHODS: Serum G-CSF level
      was detected by ELISA assay in 36 SAA-I patients. RESULTS: Pre-treatment serum G
      CSF levels of 27/36 (75%) SAA-I patients were above normal. These patients
      achieved better curative outcomes in a shorter period of treatment. CONCLUSION:
      Detection of serum G-CSF level in SAA-I patients is helpful for judging the
      clinical status and prognosis.

PMID- 11243133
TI  - [Glucose-6-phosphate dehydrogenase mutations among Cantonese revealed by
      polymerase chain reaction using dried blood spots].
AB  - OBJECTIVE: To analyze G6PD gene mutation in 168 Cantonese G6PD deficient male
      infants. METHODS: PCR products were amplified directly from dried blood spots on
      filter paper using 7 pairs of special primers followed by digestion with a
      restriction enzyme. RESULTS: Of the 168 samples, 72(42.8%) were G6PD 1376 G-->T
      mutation, 35 (20.8%) were G6PD 1388 G-->A, 30(17.9%) were G6PD 95 AG, 6(3.6%)
      were G6PD 392 G-->T, and 3(1.8%) were G6PD 1024 C-->T. No G6PD 493 A-->G and 487
      G-->A mutation were found, and 22(13.1%) were not defined. CONCLUSION: 1. The
      three G6PD mutations at 1376, 1388 and 95 were common in Cantonese. 2. Dried
      blood spots collected on filter paper provide an easy way of sample collection,
      storage and transport for the epidemiological study of inherited disease.

PMID- 11243134
TI  - [Changes in the contents of membrane phospholipid and membrane phospholipid
      asymmetry in glucose-6-phosphate dehydrogenase deficient erythrocyte].
AB  - OBJECTIVE: To study the effect of G6PD deficiency on membrane phospholipid
      structures. METHODS: Treatment of intact erythrocyte with phospholipase A2 was
      used for the membrane phospholipid asymmetry. Membrane phospholipid was
      determined by high performance liquid chromatography (HPLC). RESULTS: The
      contents of phosphatidylethanolamine (PE), phosphatidylcholine (PC),
      phosphatidylserine (PS) were 5.18 +/- 1.86, 1.51 +/- 0.58 and 5.70 +/- 1.91 mg/mg
      membrane protein, respectively, in G6PD deficient erythrocytes and were 5.59 +/-
      1.16, 2.92 +/- 0.50 and 6.64 +/- 0.92 mg/mg membrane protein, respectively, in
      normal erythrocytes. In normal erythrocytes, 17.6% +/- 2.5% PE and 57.9% +/- 4.7%
      PC were present and no PS was found on the outer leaflet of the membrane. While
      in G6PD deficient ones, 30.2% +/- 5.7% PE, 53.8% +/- 7.4% PC and 27.2% +/- 5.8%
      PS were present on the outer leaflet. CONCLUSION: Membrane phospholipid changes
      in G6PD deficient erythrocytes might be one of the factors causing hemolysis.

PMID- 11243136
TI  - [Study of hemoglobinopathy in Kashi district of Xinjiang].
AB  - OBJECTIVE: To study the hemoglobinopathy in Kashi district of Xinjiang. METHODS:
      The abnormal hemoglobin carriers were investigated with microelectrophoresis. The
      propositus of thalassemia were tested with two steps of screening technique. The
      structural analysis of abnormal hemoglobin was carried out with finger print
      analysis technique. Gene identification of thalassemia was performed with PCR/ASO
      technique. RESULTS: The incidence of hemoglobinopathy and thalassemia were 0.8%
      and 3.07%, respectively. Both were higher than the average level in the
      population of Xinjiang and the whole country. Two kinds of variant of HbJ
      Tashikuergan [alpha 19(AB1)Ala-->Glu] and HbD Punjab[P121(GH4)Glu-->Gln] were
      found in the structural analysis of 8 cases of abnormal hemoglobin. Four kinds of
      mutation: CD8(-AA),CD8/9(+G),CDs41/42(-TTCT) and IVS-I-5(G-->C) were revealed at
      the gene identification of 10 propositus of beta-thalassemia. HbJ Tashikuergan
      was firstly reported in the world, and CD8(-AA) and CDs8/9(+G) were firstly
      discovered in China. CONCLUSION: The types and distribution of abnormal
      hemoglobin and thalassemia in Kashi district were different from those in other
      areas of our country, and also unsimilar to our neighbour countries.

PMID- 11243135
TI  - [Leu 72 Pro mutation in the NADH-cytochrome b5 reductase gene found in a Chinese
      hereditary methemoglobinemia patient].
AB  - OBJECTIVE: To characterize the mutation in NADH-cytochrome b5 reductase gene in a
      Chinese hereditary methemoglobinemia patient, and elucidate the molecular basis
      of the disease. METHODS: B5R gene from a propositus was analyzed by sequencing
      the RT-PCR products as well as cDNA clones; and the results were further
      confirmed by restriction enzyme analysis of the genomic DNA fragments. RESULTS: A
      novel mutation was found at codon 72 of b5R gene from the propositus. CONCLUSION:
      Replacement of Leu with Pro at codon 72 of b5R gene is the molecular basis of the
      propositus; and the mutant allele located in 5' part of b5R gene mainly cause
      hereditary methemoglobinemia type I.

PMID- 11243138
TI  - [Effects of viral infection on hematopoiesis].

PMID- 11243137
TI  - [Efficacy of cyclosporin A in the treatment of aplastic anemia and its
      mechanism].

PMID- 11243139
TI  - [Msp I and Rsa I RFLPs of vWF gene in Chinese Han people].
AB  - OBJECTIVE: To study the Msp I and Rsa I restriction fragment length polymorphisms
      (RFLPs) in the 5' region of human von Willebrand factor gene in Chinese Han
      people. METHODS: A 226 bp amplified fragment of human vWF gene from 52 unrelated
      individuals and a 322 bp amplified fragment from 48 individuals were analyzed by
      Msp I or Rsa I digestion. RESULTS: Complete linkage disequilibrium was observed
      at both Msp I and Rsa I sites in vWF gene in Chinese Han people. The frequencies
      at the two sites were 0.20/0.80 for Msp I+/Msp I- and 0.93/0.07 for Rsa I+/Rsa I
      . The theoretical heterozygous rates were 36% and 10%, respectively. CONCLUSION:
      The Msp I and Rsa I RELPs of vWF gene are useful for genetic counseling and
      prenatal diagnosis of vWD in Chinese Han people.

PMID- 11243140
TI  - [Linkage analysis of vWD family by multi-PCR assay of microsatellite DNA in vWF
      gene].
AB  - OBJECTIVE: To set up a convenient method for analysis of the amplified fragment
      length polymorphism (amp-FLP) of two microsatellite DNA in vWF gene. METHODS:
      Multi-PCR followed by denatured PAGE and silver stain were used to analyze the
      amp-FLP of two locus (A and B) on one gel. DNA samples from 112 normal people and
      two vWD families in the Shanghai area were assayed. RESULTS: 1. seven and 5 types
      of amp-FLP were identified on loci A and B, respectively. The heterozygote rates
      were 75% and 74%, respectively. 2. Haplotypes A2/B3 and A4/B3 were found to link
      with defective vWF genes in the two vWD families, respectively. CONCLUSION: 1.
      Multi-PCR is a fast and practical method to carry out family analysis of
      inherited diseases. 2. nt1980-1990 and nt2215-2380 of vWF gene are two ideal
      genetic labels in linkage study and hereditary consultation of vWD family.

PMID- 11243141
TI  - [Detection of gene mutation and genetic analysis of a patient with type 3 von
      Willebrand disease].
AB  - OBJECTIVE: To identify gene mutations in patients with type 3 von Willebrand
      disease. METHODS: The encoding region of von Willebrand factor (vWF) gene were
      screened by polymerase chain reaction and denaturing gradient gel electrophoresis
      (PCR-DGGE). RESULTS AND CONCLUSION: The fragment of vWF gene exon 3 from a
      patient with type 3 von Willebrand disease displayed an abnormal melting
      behavior. Direct sequencing demonstrated a homozygous C-->A transition at
      nucleotide 212 in vWF gene resulting in the substitution of a stop codon for
      Ser71. The parents of the patient were heterozygous for this mutation as
      identified by PCR-DGGE and restriction endonuclease digestion analysis.

PMID- 11243142
TI  - [Four novel point mutations of factor IX gene detected by denaturing gradient gel
      electrophoresis].
AB  - OBJECTIVE: To identify factor IX gene mutations in patients with hemophilia B.
      METHODS: The coding regions, splicing junction sites and part of the 5' and 3'
      flanking regions of factor IX gene were screened by polymerase chain reaction
      (PCR) and denaturing gradient gel electrophoresis (DGGE). RESULTS: Four amplified
      fragments showed abnormal electrophoresis patterns, and sequencing of them
      demonstrated four novel point mutations including a T to G transition at
      nucleotide 10,380 resulting in intron 3 covering the splicing site, a A to G
      transition at nucleotide 30,918 resulting in a substitution of Cys for Tyr at
      codon 266 in exon 8, and a A to C transition at nucleotide 31,007 resulting in a
      substitution of Pro for Thr at codon 299 in exon 8. CONCLUSION: Detection of
      mutations by PCR, DGGE and sequencing was useful not only for understanding the
      structure function relationship of F IX, but also for the carrier detection and
      prenatal diagnosis.

PMID- 11243143
TI  - [Construction of a human factor VIII gene-containing plasmid and its expression
      in Cos-7 cells].
AB  - OBJECTIVE: To construct an eukaryotic expressing plasmid--pAd CMV Link F VIII DB
      and express it in Cos-7 cells. METHODS: An eukaryotic expressing plasmid--pAd CMV
      Link F VIII DB was constructed by inserting human factor VIII cDNA (F VIII DB,
      4.6 kb), in which most part of B domain was deleted, into an adenovirus sequence
      containing plasmid, and then Cos-7 cells were transfected with the constructed
      plasmid by liposome-mediated gene transfer method. F VIII DB mRNA, F VIII: Ag and
      F VIII: C in the transfected Cos-7 cells were assayed by RT-PCR, ELISA and one
      stage method, respectively, at 24, 48 and 72 hours (hrs) after transfection.
      RESULTS: F VIII DB mRNA was positive and, F VIII: Ag and F VIII: C were 18
      ng/10(6) cells/24 hrs and 0.6 U/10(6) cells/24 hrs, respectively at 72 hrs after
      transfection, which was comparable to 60% of the activity produced by 100
      micrograms/L F VIII in normal human plasma. CONCLUSION: The constructed plasmid
      is proved to be expressed in Cos-7 cells.

PMID- 11243144
TI  - [PTA1 monoclonal antibody induces human platelet aggregation and intra
      cytoplasmic Ca2+ elevation].
AB  - OBJECTIVE: To explore the mechanism of PTA1 monoclonal antibody (McAb) induced
      human platelet aggregation and its effect on intra-cytoplasmic Ca2+ level.
      METHODS: Platelet aggregation, ATP releasing assay and Pollock's test were used.
      RESULTS: PTA1 McAb induced human platelet aggregation in vitro, which could be
      completely inhibited by EGTA and PGI2. F(ab')2 of PTA1 McAb had no effect on CD9
      or CD41 induced platelet activation and aggregation. PTA1 McAb enhanced platelet
      intra-cytoplasmic Ca2+ elevation. CONCLUSION: PTA1 McAb inducing platelet
      aggregation is related to platelet Fc receptor and CD41/CD61 (II b/III a)
      complex, and the induced platelet intra-cytoplasmic Ca2+ elevation is resulted
      from Ca2+ influx and releasing of intracytoplasmic Ca2+ storage.

PMID- 11243145
TI  - [Type I protein C deficiency caused by a novel protein C gene mutation].
AB  - OBJECTIVE: To study the phenotype and genotype of a thrombophilia family.
      METHODS: Antigens and activities of protein C, antithrombin III, protein S,
      plasminogen and activated protein C resistance were assayed in 13 members from
      four generations of the family. RESULTS: Type I protein C deficiency was revealed
      in 5 members including the 3 members with deep vein thrombosis. All the exons and
      intron/exon junctions of the protein C gene were amplified by PCR. No abnormal
      band was found in SSCP assay. DNA sequencing identified a novel mutation 3444C-
      >A in exon VI of protein C gene leading to His134Asn. This mutation erased a Hph
      I site. PCR/Hph I analysis demonstrated that 6 members including 5 protein C
      deficiency members had the same mutations. CONCLUSION: His134Asn is a novel
      mutation causing type I protein C deficiency.

PMID- 11243146
TI  - [RBC-CR1 genotype polymorphism and RBC immune function in childhood ITP].
AB  - OBJECTIVE: To investigate the RBC immune functions in childhood idiopathic
      thrombocytopenic purpura (ITP). METHODS: RBC-CR1 polymorphism genotype, RBC
      immune function and its regulator function were detected in 22 ITP, 30 allergic
      purpura (AP) and 50 normal children by PCR and Guo Feng's method. RESULTS: 1.
      There were 18 cases of high expression (82%) and 4 of medium expression (18%) of
      RBC-CR1 genotypes in the ITP cases. The rate of the medium expression genotype
      was significantly higher in ITP than that in AP and normal children (P < 0.01).
      2. The rates of RBC-C3bRR and RBC-C3bRFER were much lower (P < 0.01), and the
      rates of RBC-ICR and RBC-C3bRFIR were significantly higher in ITP than those in
      normal children (P < 0.01). 3. RBC-CR1 genotypes in ITP were correlated
      negatively with RBC-C3bRR and RBC-C3bRFER (P < 0.05), but positively with RBC-ICR
      and RBC-C3bRFIR (P < 0.05). CONCLUSION: RBC immune participated in the
      pathogenesis of ITP.

PMID- 11243148
TI  - [Advances in the molecular biological study of hereditary antithrombin III
      deficiency].

PMID- 11243147
TI  - [Expression and purification of recombinant hirudin].
AB  - OBJECTIVE: To express the recombinant hirudin variant 1 (rHV1) with biological
      activity in prokaryotic cells and then isolate and purify the expressed products.
      METHODS: The hirudin variant 1 gene in plasmid vector pBV220 was expressed in E.
      coli strain DH5 alpha. The biological activity of rHV1 was determined with
      chromogenic substrate method. The expressed product was purified by
      ultrafiltration, DEAE-Sephadex A-50 filtration and thrombin-Sepharose 4B affinity
      chromatography. RESULTS: The expressed rHV1 accounted for approximately 16.9% of
      E. coli cell proteins with an activity of 20-30 ATU (antithrombin unit) per
      milliliter culture. The purified rHV1 showed a homogeneous band on SDS-PAGE.
      CONCLUSIONS: This is the first report in China on successful expression of
      hirudin variant 1 gene in E. coli and purification of the expressed rHV1.

PMID- 11243149
TI  - [Comparison of pharmacological effects between cultispecies Sichuan Fritillary
      bulb (F. wabueasis, F. mellea) and wild Sichuan Fritillary bulb (F.
      unibracteata)].
AB  - The ethanol extracts from the cultured Sichuan Fritillary bulb have been proved
      similar to those from the wild one in treating coughing in mice, expectoration in
      rats, asthma in guinea pigs, bronchodilation of isolated lungs in mice, and
      cyclic nucleotide(cAMP, cGMP) in the plasma and lungs of mice. The acute toxicity
      of the cultured and wild species is also similar to each other. However, in terms
      of asthma relieving and cAMP level increment in the lungs, the cultured species
      F. wabueasis is significantly superior to the wild species of Fritillary bulb.

PMID- 11243150
TI  - [Effects of nitrogen form on American ginseng leaf blight].
AB  - The effects of two nitrogen forms(NO3-N and NH4-N) on American ginseng leaf
      blight were studied using sand culture method. The results indicated that
      American ginseng leaf blight caused by Alternaria panax was reduced with NO3-N,
      while increased with NH4-N.

PMID- 11243151
TI  - [Influence of fry-processing on outward character and inner quality of volatile
      oil containing drugs such as fructus Viticis, etc].
AB  - According to the requirement of outward character in processing traditional
      Chinese drugs, five volatile oil containing drugs Fructus Viticis, Rhizoma
      Atractylodis Macrocephalae, Rhizoma Cyperi, Fructus Foeniculi and Fructus
      Aurantii were fry-processed. The conditions of frying technology were measured;
      the amounts of volatile oil before and after processing were determined with
      accurate volatile oil extractor; and the volatile oil in Rhizoma Atractylodis
      Macrocephalae and Fructus Aurantii was analyzed by means of GC.

PMID- 11243152
TI  - [Solid adsorption and stability of essential oil from pericarp of Gaultheria
      yunnaensis (Franch.) Rehd].
AB  - Experiments have been made on the solid adsorption and stability of the essential
      oil extracted from Gaultheria yunnanensis. The results show that among the
      chemical constituents of the oil, methyl salicylate accounts for 99.66%. Grain
      adsorbents of aluminum hydroxide gel have been proved useful in obtaining higher
      release rates of the oil at required temperatures as well as keeping the oil
      stable at room temperature.

PMID- 11243153
TI  - [Chemical constituents in the stem and leaf of Isodon oresbius].
AB  - Five triterpenoids were isolated from Isodon oresbius. Their structures were
      identified as ursolic acid, 2 alpha, 19 alpha-dihydroxy ursolic acid, 2 alpha, 3
      alpha, 19 alpha-trihydroxy-12-ursen-28-oic acid, 2 alpha-hydroxy oleanolic acid
      and 2 alpha, 23-dihydroxy oleanolic acid by physico-chemical constants and
      spectral analysis.

PMID- 11243154
TI  - [Chemical constituents of Pericampylus glaucus (Lam.) Merr].
AB  - Six crystalline substances were isolated from the rhizoma of Pericampylus glaucus
      and identified as epifriedelinol, melissic acid, palmatic acid, stearic acid,
      bututic acid and daucosterol.

PMID- 11243155
TI  - [Chemical constituents of flavonoids in the leaf of Ginkgo biloba L].
AB  - A compounds were isolated from the ethyl acetate extract of Ginkgo biloba leaves
      for the first time and was identified as 5,7,4'-trihydroxy-flavone by
      spectroscopic methods.

PMID- 11243156
TI  - [Isolation and structure determination of aurantiamide acetate from Veratrum
      nigrum L. var. ussuriense Nakai].
AB  - A modified dipeptide has been isolated from Veratrum nigrum var. ussuriense for
      the first time and confirmed to be aurantiamide acetate by spectroscopic
      analysis.

PMID- 11243157
TI  - [Essential oil analysis and trace element study of the roots of Piper nigrum L].
AB  - Pepper roots contain 0.39% of essential oil. By GC-MS method, 44 peaks and 22
      compounds were obtained and identified. The major component was trans
      caryophyllene. The trace metal content analysis showed that the heavy metals were
      under the safety level.

PMID- 11243158
TI  - [Determination of salidroside in eight Rhodiola species by TLC-UV spectrometry].
AB  - Quantitative determination of the salidroside in eight Rhodiola species by TLC-UV
      spectrometry is reported. The salidroside was separated on a silica GF254 TLC
      plate using CHCl3-CH3OH-H2O(26:14:3) as developing solvent and determined at
      wavelength 223.8 nm. The results show that this method in simple and convenient.

PMID- 11243159
TI  - [Scavenging action of shengmaiyin decoction on hydroxyl radical].
AB  - A study has been made on the scavenging action of Shengmaiyin Decoction and its
      ingredients Radix Ginseng, Radix Ophiopogonis and Fructus Schisandrae on hydroxyl
      radical, as well as on the relationship between the decoction and its ingredients
      using ESR spin-trapping. The results indicate that the decoction is better in
      antioxidation than its ingredients.

PMID- 11243160
TI  - [Methodology for designing pathological models of acute renal failure].
AB  - This paper reports the methodological study on the following five pathological
      models of acute renal failure (ARF): 1. glycerine-induced ARF in rats; 2.
      noradrenaline-induced ARF in dogs; 3. ARF model caused by shutting left renal
      artery in dogs; 4. hydrargyrism-induced ARF in rabbits; and 5. gentamycin-induced
      ARF in rats.

PMID- 11243161
TI  - [Observation on inhibitory effect of tetrandrine on the growth of human skin
      fibroblast in vitro].
AB  - The effect of tetrandrine on the growth of human skin fibroblasts was observed in
      vitro culture. The result revealed that tetrandrine significantly inhibited the
      growth of fibroblast. The higher the concentration of tetrandrine, the higher the
      inhibition rate, forming a time-dependent relationship. The possible value of
      tetrandrine in the treatment of hypertrophic scar is discussed.

PMID- 11243162
TI  - [Characters of semen of Curculigo plants under electron microscopic scanning].
AB  - The semens of five species of Curculigo were detected by electron microscopic
      scanning. The result shows that the surface characters of semens are useful in
      the identification of these species.

PMID- 11243163
TI  - [Resources investigation of Actinidia in Hunan Province].
AB  - Based on the resources investigation and taxonomic research on the plants of
      Actinidia in Hunan Province, 15 species and 5 varieties together with their
      distribution and utilization are reported. A key is set forth according to the
      differences among the above species and varieties.

PMID- 11243164
TI  - [Uses of DNA-based diagnostic techniques in the study of medicinal plants].

PMID- 11243166
TI  - [Microscopic identification of beimu grown in Yunnan province].
AB  - This paper deals with the microscopic identification of the bulbs of 5
      Fritillaria species from Yunnan Province, namely: F. cirrhosa, F. cirrhosa var.
      purpurea, F. cirrhosa var. viridiflava, F. delavayi and F. crassicaulis. Based on
      the shape, size, hilum and striation of the starch grain and the cuticular veins
      of the upper epidermis cell of the scales, these species could be distinguished
      obviously.

PMID- 11243165
TI  - [Resources and geographical distribution of Ganodermataceae in Guizhou province].
AB  - This paper reports the geographical distribution and medicinal value of 30
      species of Ganodermataceae produced in Guizhou Province. Of these 30 species one
      is newly discovered and 18 are expounded in respect to their geographical
      distribution.

PMID- 11243168
TI  - [Effect of environment on the teleutospore viability of Ustilago coicis].
AB  - The teleutospores of Ustilago coicis can retain their germinating power under
      indoor dry conditions for about five years. They can survive the winter in the
      fields in Beijing. Increase of soil humidity could reduce the number of
      teleutospores in soil. Rotation is an efficient method to control the head smut
      of Jobs-tears and the rotation cycle is two years minimum.

PMID- 11243167
TI  - [Effects of HE particles on medicinal plant Agastache rugosus (Fisch. et Mey.) O.
      Ktze].
AB  - The biological effect of HE particles on the seeds of Agastache rugosus was
      probed in experiments on board a retrievable satellite. The result shows that the
      germination rate of the seeds pierced by HE particles radiation appears rather
      low. The seeds hit by HE particles (piercing radiation or not) start to germinate
      two days earlier than those in the control group, and the first leaf emerges four
      to five days earlier than that in the control group. The resultant seedlings grow
      markedly faster. Variations take place in the nuclear types of chromosome. The
      yield of essential oils becomes slightly higher. No marked changes have been
      observed in the major chemical components of these oils.

PMID- 11243169
TI  - [Exploration of processing principles for fructus Psoralea].
AB  - This paper deals with the exploration of processing principles for Fructus
      Psoralea using GC method with the content of active constituents--psoralen and
      isopsoralen as the criteria. The result showed that both temperature and enzyme
      would enhance the content of psoralen and isopsoralen, and the latter was
      stronger in action than the former.

PMID- 11243171
TI  - [The absolute configuration of 13-hydroxy-entkaurenoids].
AB  - A method is suggested to determine the absolute configuration of ent-kaurene
      diterpenoids by analysing the circular dichroism spectral data of 13-hydroxy-ent
      kaurenoids.

PMID- 11243170
TI  - [Simultaneous determination of matrine and oxymatrine in jieeryin and fuyanshuan
      by RP-HPLC].
AB  - Matrine and oxymatrine in Jieeryin and Fuyanshuan were separated and determined
      by Reversed Phase High Performance Liquid Chromatography, A chromatographic
      method for the separation and determination of matrine and oxymatrine in these
      preparations was established. Chromatographic coditions: ODS column with methanol
      water-triethylamine(55:45:0.02) as the mobil phase, and UV detection at 215 nm.
      The method is simple, sensitive and accurate. This study provides the scientific
      basis for quality evaluation and quality control in making these preparations.

PMID- 11243173
TI  - [Chemical composition of Fagopyrum cymosum (Trev.) Meisn].
AB  - From the ethanolic extracts of the aerial parts of Fagopyrum cymosum, eleven
      compounds were isolated, of which eight have been identified as benzoic acid(1),
      beta-sitosterol(2),5,5'-di-alpha-furaldehyde dimethyl ether(3), p-hydroxybenzoic
      acid(4), rutin(5), quercetin(6), daucosterol(7), succinic acid(8) by
      spectroscopic methods. Compound 3 is obtained from the genus for the first time.

PMID- 11243172
TI  - [Alkaloids in Sophora alopecuroides seed and relevant tests for activity].
AB  - Seven alkaloids were isolated from the seed of Sophora alopecuroides and
      identified to be oxymatrin, oxysophocarpine, cytisine, matrine, sophocarpine,
      sophoridine and nicotine respectively by comparing chromactographic and spectral
      characteristics with authentic known compounds. Nicotine was isolated from
      Sophora for the first time. The activity of extracts and alkaloids against
      cancer, virus, dermatophytes and bacteria was carried out in vitro.

PMID- 11243174
TI  - [A preliminary study on extracellular polysaccharide isolated from fermented
      Tremella aurantia Schw. ex Fr].
AB  - TaA, the extracellular polysaccharide purified from the filtrate of fermented
      Tremella aurantia, is a water-soluble neutral polysaccharide. Gas chromatography
      of its alditol acetates has shown that TaA is composed of mannose and xylose by
      the ratio of 2.85:1. The physical and chemical properties of TaA have been
      characterized.

PMID- 11243175
TI  - [Diuretic effect of liniaoling(KLP)].
AB  - Experimental results have shown that KLP taken orally helps promote the diuretic
      action of normal Wistar rats, decrease the urine volume of debilitated rats and
      increase the urine volume of BPH rats. It has also been shown that KLP(i.v.) can
      increase the urine volume of anesthetic rats and reduce the remnant urine. In
      addition, KLP can contract the smooth muscle of rats and rabbits.

PMID- 11243176
TI  - [Protective effect of puerarin on acute cerebral ischemia in rats].
AB  - Acute incomplete brain ischemia in rats was induced by bilateral carotid artery
      occlusion(BCAO). BCAO results in severe suppression of EEG and increase of brain
      water content. Left middle cerebral artery occlusion(MCAO) in rats by electrical
      coagulation results in increase of brain water content of ipsilateral hemisphere
      and contralateral hemiparesis. The typical ischemic neuropathological damage
      emerges in both BCAO and MCAO models. Intraperitoneal injection of puerarin
      significantly helps improve all these brain ischemic disturbances.

PMID- 11243177
TI  - [Advances in the study of the identification of animal-derived materia medica in
      China].

PMID- 11243178
TI  - [Medicinal plant resources of Dipsacaceae in China].
AB  - Based on field investigation and taxonomic research on the medicinal plants of
      Dipsacaceae in China, eighteen species and four varieties of five genera in this
      family are reported. Among them, some new medicinal plant resources are
      supplemented, the Latin name of one species is revised, the distribution,
      habitats and medicinal uses of the species are spelled out and a key for the
      genus of Dipsacus is given.

PMID- 11243179
TI  - [Peroxidase and soluble protein in the leaves of Aloe vera L. var. chinensis
      (Haw.)Berger].
AB  - The peroxidase activity and soluble protein content in the leaves of Aloe vera
      var. chinensis were assayed by spectrophotometric method. The results show that
      the peroxidase activity in the upper most and lower parts of leaves is
      comparatively high. Soluble protein content decreases from top to bottom leaves.
      The results of electrophoresis of soluble protein show that the patterns of upper
      leaves have more and darker bands than those of lower leaves.

PMID- 11243180
TI  - [Contents of free amino acids and water-soluble carbohydrates in Curcuma longa L.
      at different stages of growth].
AB  - Closely related to the development of plant organs, the contents of free amino
      acids and water-soluble carbohydrates in Curcuma longa vary with the course of
      growth. The ratio of the two contents rises with the growing periods, and reaches
      a maximum in the later stages of growth.

PMID- 11243181
TI  - [Influence of processing on atractylenolide III content in Atractylodes
      macrocephala Koids].
AB  - The atractylenolide III content in different processed products of Atractylodes
      macrocephala was determined by HPLC. The result has shown that the content in the
      processed products appears higher than that in the crude herb, with the yellow
      fried product being the highest.

PMID- 11243183
TI  - [Determination of geniposide and paeoniflorin in Jiawei Xiaoyao Pills by HPLC].
AB  - The geniposide and paeoniflorin in Jiaowei Xiaoyao Pills were separated and
      determined by HPLC, with a C18 column and a mixture of CH3CN-0.1% H3PO4(13:87) as
      mobile phase. The method is simple, rapid and accurate. The components have a
      good linearity, and the average recovery with RSD(n = 5) is 101.81% + 2.38% for
      geniposide and 98.75% + 1.95% for paeoniflorin.

PMID- 11243182
TI  - [Extraction, purification and ascertainment of anti-hepatoma active principles
      for targeted preparation of radix Aconiti Kusnezoffii].
AB  - The extraction, purification, pharmacological experiments and chemical analysis
      of anti-hepatoma active principles of Radix Aconiti Kusnezoffii have been
      studied. The results show that the medicinal material Radix Aconiti Kusnezoffii
      is efficacious in inhibiting hepatoma, and the active principles are mainly made
      up of poisonous ester alkaloids. The liver targeting delivery system will be the
      first choice for its anti-hepatoma preparation, and the effective component AY3a
      is fit for the preparation of targeted microspheres.

PMID- 11243184
TI  - [Chemical constituents of Isodon pharicus (Prain) Murata].
AB  - Two compounds were isolated from Isodon pharicus. Their structures were
      elucidated as 11 beta, 13 alpha, 15 alpha-trihydroxy-entkaur-16-en-3 alpha-(beta
      D-glucoside) (named isodopharicin F) and eugenyl-beta-D-glucopyranoside by
      spectral data and chemical evidence.

PMID- 11243185
TI  - [Chemical constituents of the roots of Glycyrrhiza eurycarpa P.C.Li].
AB  - Four compounds were isolated from the roots of Glycyrrhiza eurycarpa. They were
      identified as licochalcone A, glabrol, betulic acid and beta-sitosterol by
      chemical and physical properties and spectral analysis.

PMID- 11243186
TI  - [Chemical studies on Campylotropis hirtella (Franch. Schindl.)].
AB  - From the roots of Campylotropis hirtella 6 compounds were isolated. Based on the
      extensive spectrae analysis their chemical structures were identified as beta
      sitosterol, oleanolic acid, ursolic acid, euscaphic acid, tomentic acid and
      rosamultin.

PMID- 11243187
TI  - [Determination of adenosine and thymidine in Fritillaria bulbs by ultraviolet
      spectrophotometry].
AB  - A convenient method for quantitative analysis of the nucleosides in Fritillaria
      bulbs has been developed by means of thin layer chromatography and ultraviolet
      spectrophotometry. The MeOH extracts from four species of Fritillaria were
      analyzed with this method. The results show that both adenosine and thymidine in
      the four species are quite disparate, suggesting that the nucleosides may be
      responsible for the anti-coagulative activity of Fritillaria.

PMID- 11243188
TI  - [Minor Bupleurum decoction in the treatment of viral myocarditis models].
AB  - A myocarditis model of Balb/c mice established by means of coxsackie virus type
      B3 was treated with the Minor Bupleurum Decoction. The results indicate that the
      decoction can regulate T lymphocyte subsets, influence anti-cardiac antibody
      production, help the organism to get clear of viruses, and thus plays an
      important role in treating viral myocarditis.

PMID- 11243189
TI  - [Pharmacological effect of cortex Magnoliae officinalis on digestion system].
AB  - Experiments have shown that the ethanol extract of Cortex Magnoliae Officinalis 5
      g/kg, 15 g/kg may significantly inhibit HCl-induced gastric ulcer in mice as well
      as Cassia angustifolia Leaf-induced experimental diarrhea in mice. 3 g/kg and 10
      g/kg have a marked choleretic effect on rats. These results show that Cortex
      Magnoliae Officinalis helps improve the condition of digestion.

PMID- 11243190
TI  - [Pharmacological studies on Chinese bone extract granules].
AB  - The Chinese Bone Extract Granules could enhance the immunity of mice with spleen
      deficiency, increase the serum calcium content of rats with bone loose, inhibit
      the gastrointestinal movement of mice with spleen-deficiency and improve the
      absorption of D-xylose in small intestine of rats with spleen-deficiency. The
      maximal tolerance dose for mice to take orally twice a day was greater than 50
      g/kg. The subacute toxicologic test for 6 weeks of continuous feeding to rats did
      not show any obvious toxicity.

PMID- 11243191
TI  - [An experimental study on the antistimulative and antineoplastic effects of radix
      ginseng used in combination with Fafces Trogopterus].
AB  - The animal experiment of Radix ginseng used in combination with Fafces
      Trogopterus shows. That the combination produces better antistimulative effect
      than Radix Ginseng singly, helps inhibit mouse EAC and extends the life-span of
      neoplastic mice.

PMID- 11243192
TI  - [The solid-phase synthesis of methotrexate-alpha-peptides].
AB  - Methotrexate(MTX) and the methotrexate-alpha-peptides(MTX-alpha-phenylalanine and
      MTX-alpha-arginine i.e. MTX-alpha-Phe and MTX-alpha-Arg) were prepared with the
      technique of solid-phase peptide synthesis. Its purity was verified as a single
      peak by HPLC and its molecular weight was measured by mass spectrometry. MTX
      alpha-Phe could be hydrolyzed to MTX by carboxypeptidase A. The cytotoxic effect
      of released MTX was found to be 100 times stronger than that of the peptide in
      vitro. It is suggested that MTX-alpha-Phe is a satisfactory prodrug in the
      treatment of cancer.

PMID- 11243193
TI  - [Structure determination of three saponins from the stem bark of Albizzia
      julibrissin Durazz].
AB  - Three new saponins named Julibroside J1, J2 and J3 were isolated from the stem
      bark of Albizzia julibrissin Durazz (Albizziae Cortex). Based on chemical and
      spectral methods, e.g. 1H- and 13C-NMR, DEPT, COSY CH-COSY, TOCSY, HMQC-COSY,
      HMQC-TOCSY, NOESY, HMBC, their structures have been identified as; Julibroside J1
      (one triterpene, nine sugars, two monoterpenes I); Julibroside J2(one triterpene,
      eight sugars two monoterpenes II); Julibroside J3(one triterpene, nine sugars two
      monoterpenes III).

PMID- 11243194
TI  - [The in vitro metabolism of hainanensine derivative HH07A by rat liver
      microsomes].
AB  - The metabolism of hainanensine derivative HH07A has been studied in vitro with
      rat microsomes. A method of HPLC-DAD was developed for screening the metabolites
      from the microsomal incubation system. Two metabolites were found according to
      their UV spectra. One of them was extracted and purified with preparative HPLC
      and TLC, its chemical structure was identified by UV, IR, MS and NMR.

PMID- 11243195
TI  - [Separation and determination of flavonols in the flowers of Carthamus tinctorius
      by RP-HPLC].
AB  - Carthamus tinctorius L. is a kind of traditional Chinese medicine used in the
      treatment of uterine congestion, cardio-vascular disease, thrombosis and so on.
      Eight flavonoids have been isolated from its flowers. A reversed phase HPLC
      method for the separation and determination of the three flavonols: rutin (I),
      quercetin(II) and kaempferol(III) in the flowers of Carthamus tinctorius L. is
      described. The column was 25 cm x 4.6 mm ID, packed with YWG-C18(10 microns). The
      mobile phase was a mixture of MeOH-H2O-H3PO4(48.5:51.5:0.25, pH 3.5). The flow
      rate was 1.0 ml.min-1. Daidzein was used as an internal standard. UV detection
      was performed at 360 nm. The relative standard deviation of the method was 1.1
      2.6%. The calibration curves showed good linearity over the range of 0.11-0.80
      microgram, gamma = 0.9995-0.9998 and detection limits were 2.0-20.0 ng. The
      recoveries were 97.8%-98.9% for the three flavonols. The method is simple, fast,
      sensitive and accurate and has been applied to the analysis of Carthamus
      tinctorius L. of different sources. It can also be used for the quality control
      of safflower preparations for clinical uses.

PMID- 11243196
TI  - [Artificial reconstituted pulmonary surfactant used for prevention and treatment
      of adult respiratory distress syndrome. II. Bioluminescence method for optimizing
      formulation].
AB  - Based on optimizing the formulations of artificial reconstituted pulmonary
      surfactant (APS) used for the prevention and treatment of adult respiratory
      distress syndrome (ARDS) by a surface chemical method, a quartz lung animal model
      to obtain active alveolar macrophages (AMs) was established, using a
      bioluminescence technique to optimize APS's formulation according to the free
      radical-scavenging abilities of APS. An optimal formulation was obtained, which
      showed good surface properties and free-radical-scavenging abilities. The APS
      preparation will be used in ARDS animal model test.

PMID- 11243197
TI  - [Artificial reconstituted pulmonary surfactant used for prevention and treatment
      of adult respiratory distress syndrome. III. Prevention in animal model].
AB  - Based on two major factors resulted in adult respiratory distress syndrome
      (ARDS), lack of pulmonary surfactant and damage of free radicals, an artificial
      reconstituted pulmonary surfactant (APS) was prepared. The results of prevention
      of ARDS in ARDS rats showed that APS reduced the mortality of animal model
      significantly (from 46.47% to 16.17%) and the ratio of wet/dry lung weight (from
      5.55 to 4.84). The surface properties of lung lavage of treated animals were
      improved effectively [balancing surface tension from 61.86 mN.m-1 to 47.02 mN.m
      1, (normal 43.94 mN.m-1), minimal surface tension from 30.41 mN.m-1 to 7.16 mN.m
      1(normal 3.49 mN.m-1)]. These results indicate that the APS preparation showed
      better effect on prevention of ARDS in rats.

PMID- 11243198
TI  - [Determination of rate order for degradation of drugs with nonisothermal
      stability experiment].
AB  - By a theoretical investigation of simulated nonisothermal data, the inability to
      determine the rate order for degradation of drugs with ordinary nonisothermal
      experiment was discussed. Results indicate that both rate order n and activation
      energy E can change the curvature of the c-t curve and the change caused by
      higher n can be compensated by higher E in ordinary nonisothermal experiments.
      That means a suitable E can always be assessed to fit each of the definite n (0,
      1, or 2 in our study) very well. As a result, a same set of c-t data can be well
      fitted by different combinations of n and E. This is why the rate order cannot be
      assessed in ordinary nonisothermal experiments. To overcome this deficiency, it
      is important that there have both temperature rising and lowering parts in one
      nonisothermal experiment. A new heating model, temperature rising and lowering
      program, was presented. With this new heating model, the kinetic parameters,
      including the rate order, can be obtained in one nonisothermal stability
      experiment. The ability of the new heating model to determine rate order is
      almost the same as that of isothermal experiments.

PMID- 11243199
TI  - [Autoradiography of NMDA receptors in amygdala-kindled rats with tolerance to and
      dependence on the anticonvulsant effect of clonazepam].
AB  - Mechanisms underlying tolerance to and dependence on the anticonvulsant effect of
      clonazepam are not clear. Autoradiography of the NMDA receptors in amygdala
      kindled rats with tolerance to and dependence on the anticonvulsant effect of
      clonazepam was carried out. When tolerance developed, the binding of [3H] TCP (N
      (1-thieny) cyclohexylpiperidine) to NMDA receptors was found to be increased at
      the polymorphocellular layer of the right CA1, and decreased at the molecular
      layer of the cerebellar ansiform lobule. On day 7 of the discontinuation of
      clonazepam, the binding did not change further. These changes may be responsible
      for the tolerance to and dependence on the anticonvulsant effect of clonazepam.
      However, the exact significance of these results should be further investigated.

PMID- 11243200
TI  - [Preparation and anti-HIV activity study of baicalien and its benzylated
      derivatives].
AB  - Baicalein (1) was prepared from baicalin by acid hydrolysis with yield of 24%. 5,
      6-Dibenzyl-7-hydroxyl-flanone (4) and 6-benzyl-5, 7-dihydroxyl-flanone (5) were
      obtained by using different benzylating agents, and then hydrolyzing those
      benzylated compounds. The total yield of (4) and (5) were 5.9% and 5%,
      respectively. Both 4 and 5 were less effective than baicalien on inhibition of
      HIV-1 RT in vitro.

PMID- 11243201
TI  - [Studies on the triterpene sapogenins from Albizziae Cortex].
AB  - A new sapogenin named Julibrogenin A was isolated from the stem bark of Albizzia
      julibrissin Durazz (Albizziae Cortex). Based on chemical and spectral studies,
      their structure has been identified as 21-O-(2-hydroxymethyl-6-methyl-6-methoxyl
      2,7-octadienoyl)-acacic acid. In addition, machaerinic acid lactone, machaerinic
      acid methylester, acacigenin B and julibrotriterpenoidal lactone A were also
      isolated from this plant and characterised.

PMID- 11243202
TI  - [Determination of nifedipine in human plasma by gas chromatography and its
      pharmacokinetic study].
AB  - A gas chromatographic method for the determination of nifedipine in human plasma
      is presented. Nifedipine was extracted into toluene and diazepam was used as the
      internal standard. Chromatography was performed on an OV-101 fused-silica column
      by splitless injection with an electron capture detector. The minimal detectable
      concentration in plasma was 1 ng.ml-1. The standard curve was linear in the range
      2-150 ng.ml-1 (gamma = 0.9988). The method has been applied to pharmacokinetic
      study.

PMID- 11243203
TI  - [A review of physiologically based pharmacokinetic models: development and
      applications].

PMID- 11243204
TI  - [Preliminary study on the absorption, distribution and excretion of doxophylline
      in rats].
AB  - Doxophylline, a new antibronchospastic drug, being more active and less toxic
      than aminophyline, was detected by high-performance thin layer chromatography.
      The pharmacokinetics of doxophylline have been characterized in rats, whose serum
      concentration were monitored after 100, 200, 400 mg.kg-1 oral dose. The drug was
      found to conform to a one-compartment model and can be bio-transformed quickly in
      rats. The Cmax, AUC and CL/F appeared to be dose-dependent. T1/2 (Ke) was 1.17 +/
      0.13 h after the 100 mg.kg-1 dose, 2.54 +/- 0.60 h after the 200 mg.kg-1 dose
      and 3.75 +/- 0.92 h after the 400 mg.kg-1 dose. The doxophylline concentration in
      tissues decreased rapidly. Total excretion of the drug in urine, bile and faeces
      was 5.2 per cent of the dose. Plasma protein binding was about 25 percent.

PMID- 11243205
TI  - [Correlation between motor paralysis and neurotoxicity induced by intrathecal
      dynorphin A (1-17) in rats].
AB  - Intrathecal(i.t.) injection of 10 microliters of dynorphin A(1-17) 20 nmol.L-1
      per rat resulted in irreversible hind limb paralysis and suppression of the tail
      flick reflex lasting for up to 40 h. The dual effects of dynorphin appeared 5-10
      min after the i.t. administration. Histologic examination of the spinal cord in
      the rats demonstrated dead and/or dying and degenerated motor-neurons in the
      ventral horn located predominately in the lumbar segment(a 87.2% reduction of the
      number of motor neurons, P < 0.01) and also in a lesser degree in sacral segment(
      69.6%, P < 0.05). The thoracic segment was essentially normal(-8.2%, P > 0.05).

PMID- 11243206
TI  - [Effect of enterogastric circulation of diazepam on its CNS inhibitory action in
      mice].
AB  - The present study was designed to examine whether disturbance of the
      enterogastric circulation of diazepam would obviously affect its inhibitory
      action on CNS. Intragastric administration of acidic liquid (pH 1) elicited a
      marked increase in the amount of diazepam in the gastric juice of mice 1 h after
      i.v. diazepam, as measured by HPLC method. The effects of ig acidic charcoal (2
      g.kg-1, pH 1), neutral charcoal and normal saline on diazepam-induced CNS
      depression were compared by studying the duration of hypnotic action, inhibition
      of spontaneous activity, dropping rate in rotating rod test and mortality after
      i.v. diazepam (10-40 mg.kg-1) in mice. The results showed that the animals
      receiving ig acidic charcoal recovered more rapidly from CNS depression and
      exhibited lower mortality than the animals in neutral charcoal group and normal
      saline group.

PMID- 11243207
TI  - [Inhibitory effect of matrine on lipopolysacchride-induced tumor necrosis factor
      and interleukin-6 production from rat Kupffer cells].
AB  - The effect of matrine on the lipopolysacchride (LPS)-induced tumor necrosis
      factor and interleukin-6 production from rat Kupffer cell was investigated.
      Results showed that matrine 125, 250 and 500 mg.L-1 suppressed TNF and IL-6
      production from Cal-primed Kupffer cells in the presence of lipopolysacchrides
      (LPS, 100 micrograms.L-1) in a concentration-dependent manner. Treatment with
      matrine 50 and 100 mg.kg-1 before LPS injection(3.5 mg.kg-1) markedly decreased
      mouse serum TNF and IL-6. The results suggest that matrine may have protective
      effect on LPS-induced liver injury.

PMID- 11243208
TI  - [Synthesis and bioactivity of some 3,4-diacyloxybenzopyrans].
AB  - Considerable attention is now being given to the potassium channel openers of
      benzopyrans as potential therapeutical agents for hypertension. In order to
      search for novel antihypertensive with high efficacy and low toxicity,
      integrating structural features of cromakalim and praeruptorin C, twenty-four
      compounds of 3,4-diacyloxybenzopyrans were designed and synthesized. Some of them
      exhibited hypotensive activity in Sprague Dawley rats.

PMID- 11243209
TI  - [Effects of neferine on platelet aggregation in rabbits].
AB  - Neferine (Nef), a hypotensive agent with antiarrythmic action, is a dibenzyl
      isoquinoline alkaloid isolated from a Chinese medicinal herb (Nelumbo nucifera
      Gaertn). Its effects on platelet aggregation and TXA2/PGI2 and cAMP/cGMP balance
      were studied with methods of turbidimetry and RIA. Nef was shown to significantly
      inhibit rabbit platelet aggregation induced by ADP, collagen, arachidonic acid
      (AA) and platelet-activating factor (PAF) with IC50 of 16, 22, 193 and 103
      mumol.L-1, respectively. Nef was found to increase vascular 6-keto-PGF1 alpha and
      platelet cAMP levels in dose-dependent manner, but inhibit AA stimulated TXA2
      release from platelets. Nef showed no significant effect on the platelet cGMP
      level. The results suggest that the mechanism of Nef on platelet aggregation is
      related to regulation of TXA2/PGI2 and cAMP/cGMP balance.

PMID- 11243211
TI  - [Effect of berberine on intracellular free CA2+ concentration in cultured brain
      cells].
AB  - Intracellular free calcium concentration ([Ca2+]i) was measured with Ca(2+)
      sensitive fluorescent indicator, Fura-2/AM, in cultured brain cells using AR-CM
      MIC cation measurement system, and the effects of berberine (Ber) on the changes
      in [Ca2+]i induced by CaCl2, norepinephrine, KCl and H2O2 were studied. The
      results indicate that the resting [Ca2+]i was 35 +/- 8 nmol.L-1 in Ca(2+)-free
      Hank's solution. Ber showed no effect on the resting [Ca2+]i when the
      extracellular Ca2+ were 0.01-10 mmol.L-1. Ber 1-100 mumol.L-1 dose-dependently
      inhibited norepinephrine and H2O2 induced [Ca2+]i elevation. Ber at high
      concentration (10-100 mumol.L-1) inhibited K(+)-induced [Ca2+]i elevation. This
      suggests that the inhibitory effects of Ber on norepinephrine, K(+)-, and H2O2
      induced [Ca2+]i elevation may be one of the mechanisms against cerebral ischemia.

PMID- 11243210
TI  - [Influence of intracerebroventricular injection of sodium nitroprusside L
      arginine and NG-nitro-L-arginine on cardiovascular activity in conscious rats].
AB  - In order to study the cardiovascular effect of NO in conscious rats, sodium
      nitroprusside (SNP), the precursor of NO (L-Arginine, Arg-Arg) and one of the
      inhibitor of NOS (NG-nitro-L-arginine, NNLA) were intracerebroventricularly (icv)
      injected. Our experimental results indicated that, an apparent dose-dependent
      hypertensive effect was produced by icv administration of SNP (8, 16, 32 and 32
      micrograms), a tachycardiac effect was also produced at the same time. In
      addition, hypertension and tachycardia were produced by icv L-arginine and the
      dipeptide Arg-Arg. Furthermore a hypotensive and bradycardiac effect can be
      produced by icv NNLA. These results suggest that there is a positive effect on
      cardiovascular activity due to increase of endogeneuse NO in the rat brain and a
      negative effect on cardiovascular activity due to decrease of endogeneuse NO in
      the rat brain.

PMID- 11243212
TI  - [Glutamate causes release of nitric oxide from chicken spinal cord in vitro].
AB  - Nitric oxide (NO) has been identified to have profound effects on many systems,
      especially the neural tissues. Many studies suggest that NO mediate the
      neurotoxicity of glutamate (Glu). In order to determine in vitro whether Glu
      causes release of NO from chicken spinal cord, different concentrations of Glu
      (0.1, 0.5, 1.0 mmol.L-1) were added to the primary cultured chicken spinal cord
      cells, and the quantity of NO- (the metabolism product of NO) in medium was
      detected. The result shows that Glu can enhance obviously the concentration of NO
      in primary cell cultures (212% compared with the control). If the spinal cord
      cells were pretreated with NO synthases (NOS) inhibitor--L-NOARG, the [NO-] was
      decreased compared with those treated with Glu only, and, on the contrary, the
      viability of cells was increased. All of the results above indicate that NO may
      play an important role in the neurotoxicity of Glu on nervous cells. It might be
      that Glu can instigate the activity of NO synthases, then induce a series of
      changes within cell and finally lead to the toxic effect on cells.

PMID- 11243213
TI  - [Effects of age and ginsenoside RG1 on membrane fluidity of cortical cells in
      rats].
AB  - Membrane fluidity was measured using fluorescence spectrophotometer in cortical
      cells isolated from Wistar rats of five age groups (fetal); neonatal (3 days),
      young (3 months), adult (9 months) and old (27 months). Neurons were
      enzymatically isolated and loaded with the fluorescent dye, DPH (1,6-diphenyl
      1,3,5-hexatriene). The membrane fluidity of neonatal cells was shown to be
      significantly higher (eta 1.485 +/- 0.211) than that in young cells (eta 2.220 +/
      0.169), and that in young cells was significantly higher than that in old cells
      (eta 2.842 +/- 0.143). No significant difference in fluidity, neither between
      fetal and neonatal cortical cells nor between young and adult ones was observed.
      Ginsenoside Rg1 (Rg1) is one of the important active principles of ginseng and
      shares many pharmacological effects of this plant. When treated with Rg1 (10, 20,
      40 mg.kg-1), the membrane fluidity of old cortical cells significantly increased
      (eta 2.670 +/- 0.108, 2.381 +/- 0.123, 2.000 +/- 0.101). These findings indicate
      a substantial alteration of membrane fluidity with neuronal aging. Increment of
      membrane fluidity provides an aspect in elucidating the mechanisms of Rg1's
      antiaging action.

PMID- 11243214
TI  - [A monoclonal antibody directed against an enediyne antitumor antibiotic and its
      preliminary application].
AB  - C1027, composed of an enediyne chromophore and an apoprotein of 110 amino acid
      residues, is a new highly potent macromolecular antitumor antibiotic. In order to
      prepare monoclonal antibodies (McAb) against C1027 by hybridoma technique,
      natural C1027 was inactivated by ultraviolet and coupled with human serum
      albumin, then immunized BALB/c mice. After cell fusion and screening by ELISA, a
      hybridoma secreting anti-C1027 McAb designated as F9 was obtained. McAb F9
      specifically reacted with C1027 as determined by immunoblot assay. No obvious
      difference was observed between the reactivity of McAb F9 to natural C1027 and
      that of McAb F9 to ultraviolet inactivated C1027. This result indicates that the
      ultraviolet-sensitive chromophore of C1027 may not participate in the epitope for
      McAb F9. The isotype of F9 is IgG1 and its affinity constant was found to be (2.2
      +/- 0.47) x 10(7) L.mol-1 according to Beatty's method. By clonogenic assay, McAb
      F9 neither affected the cytotoxicity of C1027 to KB cells nor blocked the
      activity of the chromophore. McAb F9 also specifically reacted with the
      recombinant truncated C1027 apoprotein in which 16 amino acid residues at the C
      terminus were deleted. This study suggests that F9 is a valuable McAb for the
      research of C1027 apoprotein engineering, C1027 related immunoconjugates and
      screening of new macromolecular antitumor substances with homology to the protein
      part of C1027.

PMID- 11243215
TI  - [Inhibition of tumor invasion and metastasis by retinoid 4-APR].
AB  - The anti-invasive and anti-metastatic effects with new retinoid 4-acetamidophenyl
      retinoate (4-APR) were studied using in vitro and in vivo experiments. 4-APR, at
      the dose of 43.3 mg.kg-1.day-1 p.o., was shown to reduce the spontaneous lung
      metastatic foci of Lewis lung carcinoma. 4-APR was also found to inhibit the
      artificial lung metastasis of B16-F10 cells by 67.9% and 36.6% and suppress the
      reconstituted basement membrane invasion of B16-F10 cells by 54.2% and 41.9% at
      the concentrations of 10(-5) mol.L-1 and 10(-6) mol.L-1, respectively.

PMID- 11243216
TI  - [Study on the synthesis and antibacterial activity of Mannich bases containing
      alpha, beta-unsaturated ketone].
AB  - Twelve Mannich bases containing alpha, beta-unsaturated ketone were synthesized
      and characterized by elemental analysis, IR, 1HNMR, UV and MS spectra. All of the
      title compounds were unreported in the literature, some of these compounds showed
      marked antibacterial activity.

PMID- 11243217
TI  - [Study on the structure-activity relationships of retinoids. II. 3D-QSAR of
      retinoids and receptor interaction].
AB  - Precise prediction of the binding constant of ligand to receptor is an important
      aspect of structure-based drug design. Almost all methods including de novo
      design and 3D database search are over concentrated on structure generation
      rather than quantitative evaluation of the binding properties of the newly
      produced molecule. Using epididymal retinoic acid binding protein (ERABP) as a
      model, we simulated the interaction between retinoids and their receptor with
      DOCK program and obtained an equation for predicting the binding constants.
      According to the docking conformers of the ligands, CoMFA was also used to deduce
      a pharmacophoric model of this series of compound.

PMID- 11243218
TI  - [Synthesis and antifungal activities of 1-(1-substitutedphenyl)-2-(1H-1,2,4
      triazol or benztriazol-1-yl)-O-(substitutedbenzyl) ethanoximes].
AB  - Twenty-nine 1-(1-substituted phenyl)-2-(1H-1,2,4-triazol or benztriazol-1-yl)-O
      (substituted benzyl) ethanoximes have been synthesized for the first time.
      Results of preliminary biological test in vitro show that most compounds have
      antifungal activities against most fungi tested. The antifungal activities of
      compounds T1, T4, T6, T11, T12, B1, B3, B4 and B6 are better than or comparable
      to the activities of the lead compound oxiconazole against some fungi.

PMID- 11243219
TI  - [Involvement of cytochrome P4503A in the monohydroxylation of ring A of
      praziquantel in rat liver microsomes].
AB  - The possibility of involvement of cytochrome P4503A (CYP3A) in the
      monohydroxylation of the ring A of praziquantel (PZQ) was studied by using CYP3A
      specific inducer dexamethasone (DEX), specific inhibitor triacetyloeandomycin
      (TAO) and the activity of erythromycin (ERY) and ethylmorphine (EMP) N
      demethylase which are known to be marker for CYP3A enzyme activity as probes. In
      the liver microsomes obtained from rats pretreated with CYP3A inducer DEX with
      TAO treatment the content of uncomplexed P450 was decreased, the activity of ERY
      and EMP N-demethylase ws reduced, and simultaneously, the rate of formation of
      ring A monohydroxylate of PZQ was inhibited. Ring A monohydroxylate formation was
      competitively inhibited by TAO and ERY. The rates of ring A monohydroxylate
      formation were strongly correlated with the activity of N-demethylase of ERY and
      EMP. These results indicate that CYP3A is involved in the monohydroxylation of
      the ring A of PZQ.

PMID- 11243220
TI  - [Separation and identification of the llungianin A and B from the root of
      Pimpinella thellungiana Wolff].
AB  - Two compounds were isolated from the roots of Pimpinella thellungiana wolff. On
      the basis of spectral analysis (UV, IR, MS, 1HNMR, 1H-1H COSY, 13CNMR, 1H-13C
      COSY, DEPT), they were identified as 2-(1-ethoxy-2-hydroxy) propyl-4
      methoxyphenol(I); 2-(1-ethoxy-2-hydroxy) propyl-4-methoxyphenyl-2-methyl-butyrate
      (II). They are new compounds named the llungianin A and B. Pharmacological tests
      showed that they have some hypotensive effects.

PMID- 11243221
TI  - [Studies on the efficacious constituents of Astragalus complanatus].
AB  - The petroleum ether extract of Astragalus complanatus R. Br. showed activity for
      lowering the transaminase levels in mice. From this extract six compounds were
      isolated. Among them five were identified as rhamnocitrin (I), formononetin (II),
      stigmasterol (IV), phosphatidylethanolamine (V) and phosphatidylinositol (VI).
      The other one was shown to be a new p-coumaroyl derivative, 11-O-p
      coumarylnepeticin. Their structures were elucidated by spectrometric and chemical
      analyses. All the six compounds were isolated from this plant for the first time.

PMID- 11243222
TI  - [Isolation and structure elucidation of longshengensin A from Peucedanum
      longshengense].
AB  - Two compounds were isolated from Peucedanum longshengense Shan et Sheh for the
      first time. Their structures were identified as longshengensin A (I) and mannitol
      (II) by physico-chemical constants and spectral analyses (UV, IR, MS, NMR and 2D
      NMR). I is a new compound with the structure of (-)-3' (s)-acetyloxy-4' (s)
      angeloyloxy-3', 4'-dihydroseselin and named longshengensin A. Its absolute
      configurations were determined by chemical correlation with khellactone.

PMID- 11243224
TI  - [Determination of liquid-crystalline transition temperature of temperature
      sensitive liposomes of futraful by 1HNMR].
AB  - 1HNMR was employed to determine the liquid-crystalline transition temperature
      (TC) of the temperature-sensitive liposomes of futraful. It is a method with high
      sensitivity, high accuracy and furnishing more information. The 1HNMR spectra
      were made and studied. The rate of peak height increase of phospholipid
      correlates to the thermotropic phase transition of liposomes. The study shows
      that the TC of DPPC-liposomes and DSPC-liposomes is 36 degrees C and 48 degrees
      C, respectively. The TC of DPPC-DSPC-liposomes correlates with the proportion of
      the amount of DPPC and DSPC. The TC is not affected by futraful. The temperature
      sensitive liposomes of futraful with TC of 41 degrees C were prepared which
      consisted of 60% DPPC and 40% DSPC.

PMID- 11243223
TI  - [Studies on HPLC method for determination of 4-methylaminoantipyrine and relative
      bioavailabilities of analgin nasal drops in human volunteers].
AB  - A new HPLC method for the determination of a metabolite of analgin, MAA (4
      methylaminoantipyrine), in plasma and its application to determine the
      bioavailabilities of analgin nasal drops in human volunteers is reported in this
      paper. A Waters Model 481 instrument was used throughout the experiment. IAA
      (isopropylaminoantipyrine) was shown to be the most suitable internal standard at
      absorption wavelength of 254 nm. A mixture of phosphate buffer (pH 5.5) and
      methanol (68:32) was used as the mobile phase with a flow rate of 2 ml.min-1, and
      YWG-C18H37 as stationary phase. Calibration curve was linear (gamma = 0.9998) in
      the concentration range of 0.1-5 micrograms.ml-1. The within day and day-to-day
      precision (RSD) of this method were 2.35% and 2.61%, respectively, with average
      recoveries of 99.3%-103.9%. No interference was found in the body fluid. The
      plasma samples of healthy volunteers were treated with acid and extracted with
      ether. The system of mobile phase and the process of blood sample treatment were
      simpler than those reported in literature. So, the method is suitable for the
      study of pharmacokinetics and clinical determination of blood level of analgin.
      The studies on bioavailabilities of analgin nasal drops were carried out in 8 men
      relative to intramuscular injection and 6 men relative to oral tablets,
      respectively, at the dose of 250 mg analgin in different preparations
      administered by cross-over method. The main pharmacokinetic parameters were shown
      in Table 3. The results indicate that analgin nasal drops exhibited a higher
      bioavailability (relative to injection) and faster absorption (relative to
      tablet). So, analgin is suitable to be developed as a nasal preparation.

PMID- 11243225
TI  - [Study on mitoxantrone albumin microspheres for liver targeting].
AB  - An optimum procedure was established for preparing mitoxantrone albumin
      microspheres (DHAQ-BSA-MS) with emulsion-heating solidification. The morphology,
      diameters, drug loading, release characteristics, stability and its distribution
      in vivo of the drug-loaded albumin microspheres were studied. The results showed
      that the surface was regular, the average diameter was 0.99 micron, mean surface
      diameter was 1.24 microns and mean volume diameter was 1.44 microns, apparent
      drug loading was 2.558 +/- 0.101 micrograms.mg-1 (n = 5), effective drug loading
      was 1.503% +/- 0.127% (n = 5), embedding ratio was 92.82% +/- 6.48% (n = 5), and
      the release characteristics were in accord with "biphase kinetics equation": 1 -
      Q = 0.6428e-0.2132t + 0.3988e-0.00150t (gamma 1 = -0.9951, gamma 2 = -0.9982);
      T1/2 alpha = 3.250 h, T1/2 beta = 461.7 h. The stability of the drug-loaded
      albumin microspheres was good after three months storage at room temperature. The
      results determined by HPLC showed that the drug accumulated about 77.6% +/- 1.38%
      of the dose in the liver 20 minutes after intravenous injection to mice. This
      indicates that DHAQ-BSA-MS showed remarkable targeting for liver, and it seems to
      have important value for increasing the antihepatoma effect and decreasing the
      toxicity of mitoxantrone.

PMID- 11243227
TI  - Doctors lying.

PMID- 11243226
TI  - [Antisecretory effect of dl-(15R)-15 methyl-PGE2 methyl ester (PG6E) on perfusing
      rats in vivo].
AB  - The antisecretion effect of dl-(15R)-15 methyl-PGE2 methyl ester (PG6E) was
      studied in perfusing rats in vivo. The results showed that PG6E at the dose 0.1
      mg.kg-1 decreased markedly the acid secretion and antagonized the gastric acid
      secretion induced by histamine, pilocarpin and pentagastrin in rats. This action
      of PG6E appeared to be similar to that of cimetidine (40 mg.kg-1).

PMID- 11243229
TI  - Health Care Hall of Fame past inductees.

PMID- 11243228
TI  - First U.S. hospital had humble start.

PMID- 11243230
TI  - A taxing debate. City's bid to force hospital to pay up resurrects exemption
      issue.

PMID- 11243231
TI  - UK cancer charities discuss merger.

PMID- 11243232
TI  - Taxanes: 'more research needed'.

PMID- 11243233
TI  - Improved palliation 'would halt demand for euthanasia'.

PMID- 11243234
TI  - Comments on: cylopentenyl cytosine inhibits cytidine triphosphate synthetase in
      paediatric acute non-lymphocytic leukaemia: a promising target for chemotherapy.
      A.C. Verschuur et al. Eur J Cancer 2000, 36, 627-635.

PMID- 11243235
TI  - The necessity to discriminate lipofuscin from melanins.

PMID- 11243236
TI  - A visitor's impressions of major environmental toxicity issues in the Mercosur.

PMID- 11243238
TI  - Adults with fast-discharges absence seizures.

PMID- 11243239
TI  - Barriers to participation in randomised controlled trials.

PMID- 11243240
TI  - Recurrent ATM mutations in T-PLL on diverse haplotypes: no support for their
      germline origin.

PMID- 11243241
TI  - Locus-specific regulation of HLA-A and HLA-B expression is not determined by
      nucleotide variation in the X2 box promoter element.

PMID- 11243242
TI  - Determination of oxymetazoline hydrochloride and decomposition products by high
      performance liquid chromatography.
AB  - An HPLC method for the separation of the oxymetazoline hydrochloride and the
      products of its decomposition was developed and validated. The determination was
      performed with a LiChrospher RP-18 column, mobile phase of methanol-H2O
      triethylamine-sodium acetate (1 mol l(-1))-acetic acid (1.06 kg l(-1))
      (130:60:6:2:1). UV detector set at 280 nm and antazoline methanesulfonate as an
      internal standard.

PMID- 11243243
TI  - HPLC method for the determination of oxytocin in pharmaceutical dosage form and
      comparison with biological method.
AB  - Conditions have been established for the determination of oxytocin by the HPLC
      method; the method has been validated. The results of HPLC determinations are
      compared with those obtained by the biological method.

PMID- 11243244
TI  - The stability of 6-mercaptopurine riboside in neutral and basic medium.
AB  - The kinetics of hydrolysis of 6-mercaptopurine riboside (R-6-MP) was studied in
      aqueous solutions over the pH range of 6.11-12.13 at 353 K. The decomposition was
      investigated by HPLC method. At the pH range from 6.11 to 12.13 hydrolysis of 6
      mercaptopurine riboside includes: spontaeous hydrolysis of non-protonated R-6-MP
      molecules mono- and di-anions R-6-MP molecules under the effect of water.

PMID- 11243245
TI  - Electrophoretic properties of beta-lactam and serum protein conjugates.
AB  - Beta-lactam antibiotics can easy bind to protein. Available information on the
      nature of the conjugates is rather poor. In this study, agarose electrophoresis
      was used to determine and comparison physicochemical properties of the complexes.
      Benzylpenicillin, ampicillin, cefoperazone, cefotaxime, ceftazidime, cefuroxime,
      ceftriaxone, imipenem and serum protein were used for free generation drug
      protein conjugates. Agarose electrophoresis shows heterogeneous migration of the
      conjugates. Interestingly-binding of benzylpenicillin and ampicillin exerts an
      effect on electrophoretic migration of albumin and globulin, but others--only
      serum albumin. Binding of ampicillin shows down migration of all anionic
      fractions of plasma protein, benzylpenicillin--anionic and cationic. Otherwise-
      migration of albumin was accelerate by others. This finding can explain higher
      frequency of penicillins hypersensitivity than cephalosporins, carbapenems or
      monobaktams. The commercially available and cheap procedure allows to execute the
      screening of physicochemical properties, which exert an effect on electrophoretic
      mobility of protein i.e. electric charge and molecule length (Stockes's
      diameter). Therefore, the electrophoretic mobility modification probably reflects
      the transformation of molecular weight, charge and space structure serum proteins
      by binding of beta-lactam antibiotics.

PMID- 11243246
TI  - Influence of ascorbic acid on cytotoxic activity of copper and iron ions in
      vitro.
AB  - We investigated survival of two kinds of human embryonic cells (CLV102, Lu106)
      and human melanoma cells (Mel8) exposed to exogenous iron and copper ions in the
      absence or in the presence of ascorbic acid, catalase and superoxide dismutase.
      Iron ions produced cytotoxicity towards both kinds of cells dependent on its
      concentration. Catalase suppressed the cytotoxicity induced by iron ions in Lu106
      cells. whereas in CLV102 and Mel8 cells, was ineffective. By contrast, superoxide
      dismutase abolished the cytotoxicity of iron ions towards CLV102 cells, whereas
      in Lu106 and Mel8 cells, was ineffective. The mixture of iron ions with ascorbic
      acid was less cytotoxic than iron ions themselves or ascorbic acid itself, only
      in CLV102 and Lu106 cells. Ascorbic acid enhanced drastically cytotoxic effect of
      copper ions in all kinds of cells.

PMID- 11243247
TI  - The study of organic nitrates, part IV. Chemical and pharmacological study of N
      (1-methylethyl)-3-(1-naphthalenyloxy)-2-nitroxypropylamine--potential NO donor.
AB  - The reaction of N-(1-methylethyl)-3-(1-naphthalenyloxy)-2-nitroxypropylamine
      (nitrate analogue of propranolol) with hydrochloride of ethyl ester of L-cysteine
      at pH 7.7, temp. 37 degrees C was studied. The course of the reaction was
      monitored by HPLC method. It was found that at these conditions the substrates
      react and the main product of the decomposition of the nitrate of propranolol
      analogue is propranolol, nitrate and nitrite ions. The reaction has been
      described qualitatively and quantitatively. The influence of nitrate analogue of
      propranolol and propranolol alone on arterial blood pressure and heart rate in
      normotensive and hypertensive rats (SHR) was also studied. It has been found that
      both compounds exert a similar effect.

PMID- 11243249
TI  - Evaluation of properties microcrystalline chitosan as a drug carrier. Part 1. In
      vitro release of diclofenac from mictocrystalline chitosan hydrogel.
AB  - The influence of microcrystalline chitosan hydrogel, alone (MCCh) as well as in
      combination with methylcellulose (MC) or Carbopol (CP), on the release of
      diclofenac free acid (DA) and its salt (DS) was studied in vitro. Commercial
      Olfen gel (Mepha Ltd., Switzerland) was applied as a reference preparation. The
      influence of hydrophilizing agents (1,2-propylene glycol and glycerol) and
      methycellulose hydrogel on the rheological properties of the vehicle and on the
      release of drug from modified MCCh hydrogel was studied. The quantity of the
      released substance was determined by UV-spectroscopy. The results confirmed that
      release was dependent on the chemical character of the drug and on the type of
      vehicle. The process of diclofenac release from MCCh hydrogels as well as from
      Carbopol hydrogels runs in two phases. The first phase is characterised by rapid
      release whereas in the second phase the release is much slower. The most suitable
      basis for diclofenac is microcrystalline chitosan hydrogel with addition
      glycerol, 1,2-propylene glycol, and methylcellulose hydrogel.

PMID- 11243248
TI  - Quantitative analysis of structure-activity relationship in the acridine series.
      Part 2: Antitumor 9-thiadiazolo-acridine derivatives.
AB  - Synthesis and activity, vs. leukaemia cells of new 9-thiadiazolo acridine
      derivatives are reported. In addition, electronic properties and molecular
      structure are correlated with biological activity of these molecules. Results are
      in agreement with the capability of drugs to intercalate into DNA.

PMID- 11243250
TI  - Effects of oral contraceptive norethindrone on blood-lipid and lipid peroxidation
      parameters.
AB  - Considering importance of the lipophilicity of norethindrone (log P=2.97), a
      significant contributor to its mechanism of action, interaction of the drug with
      total lipids of goat whole blood have been investigated using phospholipid
      binding, fatty acid composition and peroxidation phenomena as the parameters
      under investigation. The objective was to derive an insight into the
      pharmacodynamic behavior of the drug by correlating biological activity with drug
      induced changes in lipid constituents. Significant loss in phospholipid along
      with changes in fatty acid cotmposition was observed after incubation of whole
      blood with norethindrone at 56 ng/ml (effective contraceptive concentration in
      blood) in varying periods of time. This may be ascribed to binding affinity of
      norethindrone with lipid constituents in blood. Lipid binding potential of the
      drug may have a role in its therapeutic effect. Lipid peroxidation induction
      potential of norethindrone was quantitatively measured in the context of its
      toxicity. The results reveal that northindrone caused significant extent of lipid
      peroxidation. Ascorbic acid, a promising antioxidant, at equivalent human dose
      levels of 250 mg and 500 mg could significantly reduce norethindrone induced
      lipid peroxidation.

PMID- 11243251
TI  - Effect of thiol drugs on the oxidative hemolysis in human erythrocytes.
AB  - The effect of different thiol drugs and 2-methyl-thiazolidine-2,4-dicarboxylic
      acid on the oxidative stress, induced by hydrogen peroxide, was examined in human
      erythrocytes. The results indicated that captopril (CA), methimazole, N
      acetylcysteine (NAC), penicillamine and precursor of L-cysteine 2-methyl
      thiazolidine-2,4-dicarboxylic acid (CP) might protect the erythrocyte membrane
      against lipid peroxidation in the experimental conditions. Captopril, methimazole
      and penicillamine had the strongest antioxidative properties at the concentration
      level of 0.5 mM. The protective effects gradually decreased at higher and lower
      concentrations of these drugs. Contrary, the antioxidative properties of N
      acetylcysteine increased with its levels growing in the reaction mixture, and
      only N-acetylpenicillamine did not protect erythrocytes against oxidative
      damages. The effect of 2-methyl-thiazolidine-2,4-dicarboxylic acid showed in
      these in vitro experimental conditions that it could act as an antioxidant at the
      concentration as high as 5 mM and higher.

PMID- 11243252
TI  - Lidocaine as a protective agent during pancreas cold ischemia.
AB  - Pancreatic islet transplantation in humans is a promising alternative for
      substitutive insulin therapy of IDDM (Insulin Dependent Diabetes Mellitus).
      Storage of harvested organs is a one of the most important factors, which
      influence efficacy of islet isolation process. In this sense, appropriate
      pancreas storage is the main point the successful pancreatic islet isolation. The
      purpose of the present study was to find out whether lidocaine, a well known
      membrane stabilizer and PLA2 (phospholipase A2) inhibitor could be applied in
      pancreas preservation for protection of endo- and exocrine pancreatic tissue from
      cells damage which occurs during and after storage. For this purpose, the effects
      of lidocaine on 1) viability and 2) endocrine function of pancreatic islets,
      isolated from pancreases exposed to cold ischemia, were investigated in this
      study. Our study showed hat lidocaine, injected intraductally before pancreas
      harvesting, improves efficacy of islet isolation. We found that the yields of
      islets in the groups treated with lidocaine were significantly higher when
      compared with controls. Glucose challenge test performed on these islets
      indicated that after the treatment with lidocaine, islets were more sensitive to
      glucose stimulation when compared with control islets, although the metabolic
      activity estimated by MTT test was comparable in both groups. In summary, donor
      pretreatment with lidocaine seems to be the safe method of protection of
      preserved pancreases from cell damage, caused by membranes destruction during
      cold ischemia.

PMID- 11243253
TI  - Development of a computer system in search of antifertility drug from indigenous
      plants.
AB  - Recent advancement in computer technology has increased the application of
      database in identification and verification systems used in research of
      indigenous drugs. To overcome some of the drawbacks of existing knowledge
      (systems) we have developed a computer version of a key for interfacing with pre
      existing knowledgebase. Appearance of different types of biological databases on
      the World Wide Web (WWW) and hypertext links between them has made a large amount
      of information easily accessible to biologists. Storage of explicitly specified
      biological relationship between different entities as discrete entries can allow
      additional identification capabilities. These systems are designed to detect the
      identity of a natural product when it is unknown or to verify the product
      identity when an antifertility products is provided. We have built a database
      about the cytoskeleton that explores the natural product approach as
      antifertility drug and the gap in existing knowledge. The stored information is
      displayed along with other retrieved information. The system is capable to search
      for entities with specified properties. It is extensible so that new types of
      relationships may be incorporated.

PMID- 11243254
TI  - Small, overlapping tectonic keratoplasty involving graft host junction of
      penetrating keratoplasty.

PMID- 11243255
TI  - Hyperhomocysteinemia: a risk factor for central retinal vein occlusion.

PMID- 11243256
TI  - Cyanobacterial-bacterial mat consortia: examining the functional unit of
      microbial survival and growth in extreme environments.
AB  - Cyanobacterial-bacterial consortial associations are taxonomically complex,
      metabolically interactive, self-sustaining prokaryotic communities representing
      pioneer and often the only biota inhabiting extreme aquatic and terrestrial
      environments. Laminated mats and aggregates exemplify such communities. The
      fossil record indicates that these associations represent the earliest extant
      inhabitants and modifiers (i.e. anoxic to oxic conditions) of the Earth's
      biosphere. Present-day consortia flourish in physically and chemically stressed
      environments, including nutrient-deplete, hypersaline, calcified, desiccated and
      high-irradiance ecosystems ranging from the tropics to polar regions. Consortial
      members exhibit extensive metabolic diversification, but have remained
      structurally simple. Structural simplicity, while advantageous in countering
      environmental extremes, presents a 'packaging problem' with regard to
      compartmentalizing potentially cross-inhibitory aerobic versus anaerobic growth
      processes. To circumvent these metabolic constraints, phototrophic cyanobacteria
      and microheterotrophs orient along microscale chemical (i.e. O2, pH, Eh)
      gradients to meet and optimize the biogeochemical processes (C, N, S cycling)
      essential for survival, growth and the maintenance of genetic diversity, needed
      to sustain life. Microscale ecophysiological, analytical, molecular
      (immunological and nucleic acid) techniques have helped to develop a mechanistic
      basis for understanding consortial growth and survival under extreme
      environmental conditions on Earth. Consortia are ideal model systems for
      developing a process-based understanding of the structural and functional
      requirements for life in extreme environments representative of the Earth's
      earliest biosphere and possibly other planets.

PMID- 11243257
TI  - Different portions of the maize root system host Burkholderia cepacia populations
      with different degrees of genetic polymorphism.
AB  - In order to acquire a better understanding of the spatial and temporal variations
      of genetic diversity of Burkholderia cepacia populations in the rhizosphere of
      Zea mays, 161 strains were isolated from three portions of the maize root system
      at different soil depths and at three distinct plant growth stages. The genetic
      diversity among B. cepacia isolates was analysed by means of the random amplified
      polymorphic DNA (RAPD) technique. A number of diversity indices (richness,
      Shannon diversity, evenness and mean genetic distance) were calculated for each
      bacterial population isolated from the different root system portions. Moreover,
      the analysis of molecular variance (AMOVA) method was applied to estimate the
      genetic differences among the various bacterial populations. Our results showed
      that, in young plants, B. cepacia colonized preferentially the upper part of the
      root system, whereas in mature plants, B. cepacia was mostly recovered from the
      terminal part of the root system. This uneven distribution of B. cepacia cells
      among different root system portions partially reflected marked genetic
      differences among the B. cepacia populations isolated along maize roots on three
      distinct sampling occasions. In fact, all the diversity indices calculated
      indicated that genetic diversity increased during plant development and that the
      highest diversity values were found in mature maize plants, in particular in the
      middle and terminal portions of the root system. Moreover, the analysis of RAPD
      patterns by means of the AMOVA method revealed highly significant divergences in
      the degree of genetic polymorphism among the various B. cepacia populations.

PMID- 11243258
TI  - Web alert. Microbial culture collections.

PMID- 11243259
TI  - Mannuronan C-5 epimerases and cellular differentiation of Azotobacter vinelandii.
AB  - Differentiation in Azotobacter vinelandii involves the encystment of the
      vegetative cell under adverse environmental circumstances and the germination of
      the resting cell into the vegetative state when growth conditions are
      satisfactory again. Morphologically, the encystment process involves the
      development of a protective coat around the resting cell. This coat partly
      consists of multiple layers of alginate, which is a copolymer of beta-D
      mannuronic acid (M) and alpha-L-guluronic acid (G). Alginate contributes to coat
      rigidity by virtue of a high content of GG blocks. Such block structures are
      generated through a family of mannuronan C-5 epimerases that convert M to G after
      polymerization. Results from immunodetection and light microscopy, using stains
      that distinguish between different cyst components and types, indicate a
      correlation between cyst coat organization and the amount and appearance of
      mannuronan C-5 epimerases in the extracellular medium and attached to the cells.
      Specific roles of individual members of the epimerase family are indicated.
      Calcium and magnesium ions appear to have different roles in the structural
      organization of the cyst coat. Also reported is a new gene sharing strong
      sequence homology with parts of the epimerase-encoded R-modules. This gene is
      located within the epimerase gene cluster of Azotobacter vinelandii.

PMID- 11243260
TI  - Crystal ball: leading scientists in the field of environmental microbiology
      consider the technical and conceptual developments that they believe will drive
      innovative research during the first years of the new millennium.

PMID- 11243261
TI  - An evaluation of terminal-restriction fragment length polymorphism (T-RFLP)
      analysis for the study of microbial community structure and dynamics.
AB  - A systematic evaluation of the value and potential of terminal-restriction
      fragment length polymorphism (T-RFLP) analysis for the study of microbial
      community structure has been undertaken. The reproducibility and robustness of
      the method has been assessed using environmental DNA samples isolated directly
      from PCB-polluted or pristine soil, and subsequent polymerase chain reaction
      (PCR) amplification of total community 16S rDNA. An initial investigation to
      assess the variability both within and between different polyacrylamide gel
      electrophoresis (PAGE) runs showed that almost identical community profiles were
      consistently produced from the same sample. Similarly, very little variability
      was observed as a result of variation between replicate restriction digestions,
      PCR amplifications or between replicate DNA isolations. Decreasing concentrations
      of template DNA produced a decline in both the complexity and the intensity of
      fragments present in the community profile, with no additional fragments detected
      in the higher dilutions that were not already present when more original template
      DNA was used. Reducing the number of cycles of PCR produced similar results. The
      greatest variation between profiles generated from the same DNA sample was
      produced using different Taq DNA polymerases, while lower levels of variability
      were found between PCR products that had been produced using different annealing
      temperatures. Incomplete digestion by the restriction enzyme may, as a result of
      the generation of partially digested fragments, lead to an overestimation of the
      overall diversity within a community. The results obtained indicate that, once
      standardized, T-RFLP analysis is a highly reproducible and robust technique that
      yields high-quality fingerprints consisting of fragments of precise sizes, which,
      in principle, could be phylogenetically assigned, once an appropriate database is
      constructed.

PMID- 11243262
TI  - Modification of the aggregation behaviour of the environmental Ralstonia eutropha
      like strain AE815 is reflected by both surface hydrophobicity and amplified
      fragment length polymorphism (AFLP) patterns.
AB  - After inoculation of the plasmid-free non-aggregative Ralstonia eutropha-like
      strain AE815 in activated sludge, followed by reisolation on a selective medium,
      a mutant strain A3 was obtained, which was characterized by an autoaggregative
      behaviour. Strain A3 had also acquired an IncP1 plasmid, pLME1, co-aggregated
      with yeast cells when co-cultured, and stained better with Congo red than did the
      AE815 strain. Contact angle measurements showed that the mutant strain was
      considerably more hydrophobic than the parent strain AE815, and scanning electron
      microscopy (SEM) revealed the production of an extracellular substance. A similar
      hydrophobic mutant (AE176R) could be isolated from the AE815-isogenic R. eutropha
      like strain AE176. With the DNA fingerprinting technique repetitive extragenic
      palindromic-polymerase chain reaction (REP-PCR), no differences between these
      four strains, AE815, A3, AE176 and AE176R, could be revealed. However, using the
      amplified fragment length polymorphism (AFLP) DNA fingerprinting technique with
      three different primer combinations, small but clear reproducible differences
      between the banding patterns of the autoaggregative mutants and their non
      autoaggregative parent strains were observed for each primer set. These studies
      demonstrate that, upon introduction of a strain in an activated sludge microbial
      community, minor genetic changes readily occur, which can nevertheless have major
      consequences for the phenotype of the strain and its aggregation behaviour.

PMID- 11243264
TI  - Examination of two years of community dynamics in an anaerobic bioreactor using
      fluorescence polymerase chain reaction (PCR) single-strand conformation
      polymorphism analysis.
AB  - The structures of the bacterial and archaeal communities in an anaerobic digester
      were monitored over a 2 year period. The study was performed on a fluidized bed
      reactor fed with vinasse. The objective was to characterize the population
      dynamics over a long time period under constant environmental parameters. Total
      bacterial and archaeal populations were measured independently by fluorescence
      based polymerase chain reaction (PCR) single-strand conformation polymorphism
      (SSCP) analysis using an automated DNA sequencer. With the current level of
      accuracy, the technique was able to monitor 45 bacterial and seven archaeal 16S
      rDNA molecules. The community dynamics were compared with molecular inventories
      of the microbial community based on 16S rDNA sequences done at the beginning of
      the study. The six archaeal and the 22 most frequent bacterial operational
      taxonomic units (OTUs) identified were associated with their SSCP peak
      counterparts. Overall, the data indicated that, throughout the period of the
      study, rapid significant shifts in the species composition of the bacterial
      community occurred, whereas the archaeal community remained relatively stable.

PMID- 11243263
TI  - Role of commensal relationships on the spatial structure of a surface-attached
      microbial consortium.
AB  - A flow cell-grown model consortium consisting of two organisms, Burkholderia sp.
      LB400 and Pseudomonas sp. B13(FR1), was studied. These bacteria have the
      potential to interact metabolically because Pseudomonas sp. B13(FR1) can
      metabolize chlorobenzoate produced by Burkholderia sp. LB400 when grown on
      chlorobiphenyl. The expected metabolic interactions in the consortium were
      demonstrated by high performance liquid chromatography (HPLC) analysis. The
      spatial structure of the consortium was studied by fluorescent in situ rRNA
      hybridization and scanning confocal laser microscopy. When the consortium was fed
      with medium containing a low concentration of chlorobiphenyl, microcolonies
      consisting of associated Burkholderia sp. LB400 and Pseudomonas sp. B13(FR1)
      bacteria were formed, and separate Pseudomonas sp. B13(FR1) microcolonies were
      evidently not formed. When the consortium was fed citrate, which can be
      metabolized by both species, the two species formed separate microcolonies. The
      structure development In the consortium was studied online using a gfp-tagged
      Pseudomonas sp. B13(FR1) derivative. After a shift In carbon source from citrate
      to a low concentration of chlorobiphenyl, movement of the Pseudomonas sp.
      B13(FR1) bacteria led to a change in the spatial structure of the consortium from
      the unassociated form towards the associated form within a few days. Experiments
      Involving a gfp-based Pseudomonas sp. B13(FR1) growth activity reporter strain
      Indicated that chlorobenzoate supporting growth of Pseudomonas sp. B13(FR1) is
      located close to the Burkholderia sp. LB400 microcolonies in chlorobiphenyl-grown
      consortia.

PMID- 11243265
TI  - The mechanism of killing and exiting the protozoan host Acanthamoeba polyphaga by
      Legionella pneumophila.
AB  - The ability of Legionella pneumophila to cause legionnaires' disease is dependent
      on its capacity to replicate within cells in the alveolar spaces. The bacteria
      kill mammalian cells in two phases: induction of apoptosis during the early
      stages of infection, followed by an independent and rapid necrosis during later
      stages of the infection, mediated by a pore-forming activity. In the environment,
      L. pneumophila is a parasite of protozoa. The molecular mechanisms by which L.
      pneumophila kills the protozoan cells, after their exploitation for intracellular
      proliferation, are not known. In an effort to decipher these mechanisms, we have
      examined induction of both apoptosis and necrosis in the protozoan Acanthamoeba
      polyphaga upon infection by L. pneumophila. Our data show that, although A.
      polyphaga undergoes apoptosis following treatment with actinomycin D, L.
      pneumophila does not induce apoptosis in these cells. Instead, intracellular L.
      pneumophila induces necrotic death in A. polyphaga, which is mediated by the pore
      forming activity. Mutants of L. pneumophila defective in expression of the pore
      forming activity are indistinguishable from the parental strain in intracellular
      replication within A. polyphaga. The parental strain bacteria cause necrosis
      mediated lysis of all the A. polyphaga cells within 48 h after infection, and all
      the intracellular bacteria are released into the tissue culture medium. In
      contrast, all cells infected by the mutants remain intact, and the intracellular
      bacteria are 'trapped' within A. polyphaga after the termination of intracellular
      replication. Failure to exit the host cell after termination of intracellular
      replication results in a gradual decline in the viability of the mutant strain
      bacteria within A. polyphaga starting 48h after infection. Our data show that the
      pore-forming activity of L. pneumophila is not required for intracellular
      bacterial replication within A. polyphaga but is required for killing and exiting
      the protozoan host upon termination of intracellular replication.

PMID- 11243266
TI  - Field-scale remediation of atrazine-contaminated soil using recombinant
      Escherichia coli expressing atrazine chlorohydrolase.
AB  - We performed the first field-scale atrazine remediation study in the United
      States using chemically killed, recombinant organisms. This field study compared
      biostimulation methods for enhancing atrazine degradation with a novel
      bioaugmentation protocol using a killed and stabilized whole-cell suspension of
      recombinant Escherichia coli engineered to overproduce atrazine chlorohyrolase,
      AtzA. AtzA dechlorinates atrazine, producing non-toxic and non-phytotoxic
      hydroxyatrazine. Soil contaminated by an accidental spill of atrazine (up to
      29,000 p.p.m.) supported significant populations of indigenous microorganisms
      capable of atrazine catabolism. Laboratory experiments indicated that
      supplementing soil with carbon inhibited atrazine biodegradation, but inorganic
      phosphate stimulated atrazine biodegradation. A subsequent field-scale study
      consisting of nine (0.75m3) treatment plots was designed to test four treatment
      protocols in triplicate. Control plots contained moistened soil; biostimulation
      plots received 300p.p.m. phosphate; bioaugmentation plots received 0.5% (w/w)
      killed, recombinant E. coli cells encapsulating AtzA; and combination plots
      received phosphate plus the enzyme-containing cells. After 8 weeks, atrazine
      levels declined 52% in plots containing killed recombinant E. coli cells, and 77%
      in combination plots. In contrast, atrazine levels in control and biostimulation
      plots did not decline significantly. These data indicate that genetically
      engineered bacteria overexpressing catabolic genes significantly increased
      degradation in this soil heavily contaminated with atrazine.

PMID- 11243267
TI  - Changes in the community structure of ammonia-oxidizing bacteria during secondary
      succession of calcareous grasslands.
AB  - The community structure of beta-subclass Proteobacteria ammonia-oxidizing
      bacteria was determined in semi-natural chalk grassland soils at different stages
      of secondary succession. Both culture-mediated (most probable number; MPN) and
      direct nucleic acid-based approaches targeting genes encoding 16S rRNA and the
      AmoA subunit of ammonia monooxygenase were used. Similar shifts were detected in
      the composition of the ammonia oxidizer communities by both culture-dependent and
      independent approaches. A predominance of Nitrosospira sequence cluster 3 in
      early successional fields was replaced by Nitrosospira sequence cluster 4 in late
      successional fields. The rate of this shift differed between the two areas
      examined. This shift occurred in a background of relative stability in the
      dominant bacterial populations in the soil, as determined by domain-level
      polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE).
      Molecular analysis of enrichment cultures obtained using different ammonia
      concentrations revealed biases towards Nitrosospira sequence cluster 3 or
      Nitrosospira sequence cluster 4 under high- or low-ammonia conditions
      respectively. High-ammonia MPNs suggested a decease in ammonia oxidizer numbers
      with succession, but low-ammonia MPNs and competitive PCR targeting amoA failed
      to support such a trend. Ammonia turnover rate, not specific changes in plant
      diversity and species composition, is implicated as the major determinant of
      ammonia oxidizer community structure in successional chalk grassland soils.

PMID- 11243268
TI  - Joseph E. Murray--Nobel Prize for organ transplantation.

PMID- 11243269
TI  - Alcohol consumption and chronic pancreatitis.

PMID- 11243270
TI  - The effect of small amounts of alcohol on the clinical course of chronic
      pancreatitis.
AB  - OBJECTIVE: To investigate the hypothesis that an increasing intake of alcohol
      accelerates the course of chronic pancreatitis. PATIENTS AND METHODS: In this
      retrospective record analysis and subsequent prospective follow-up of 372
      patients with chronic pancreatitis, we separately compared the clinical course of
      chronic pancreatitis among the following patients: those with early-onset
      idiopathic chronic pancreatitis and no alcohol intake (group A [n=25]) and those
      with late-onset idiopathic chronic pancreatitis and no alcohol intake (group B
      [n=41]), low alcohol intake (< 50 g/d) (group C [n=57]), and high alcohol intake
      (> or = 50 g/d) (group D [n=249]). From medical records, physical examinations,
      questionnaires, death certificates, or autopsy reports, we obtained information
      on sex, age, signs and symptoms (pain severity, calcification, endocrine and
      exocrine insufficiency), complications, surgery, and survival. RESULTS: Group D
      had the highest percentage of men (72%). At the onset of chronic pancreatitis,
      patients in group A were significantly younger than those in groups B, C, and D
      (P<.05), and severity of pain was significantly greater in patients in group A
      than in groups B, C, and D (P<.05). The percentage of patients who eventually
      developed endocrine or exocrine insufficiency was similar in all groups. Among
      patients in groups B, C, and D, an increasing intake of alcohol from zero to less
      than 50 g/d to more than 50 g/d was associated with earlier inception of disease
      (P<.001). Pain prevalence at onset was less in group B patients than in patients
      in groups C and D (P<.05). Intake of a large amount of alcohol (group D)
      shortened time to calcification and survival (P<.05). In addition, patients in
      group D had more complications (fistulas, pseudocysts, abscesses, and biliary
      obstruction) (P<.05) than those in groups A and B. More patients in group A
      underwent pancreatic surgery compared with patients in groups B and C.
      CONCLUSIONS: Among patients with onset of chronic pancreatitis after age 35
      years, alcohol intake, even less than 50 g/d, induced earlier disease
      characterized by more frequent severe pain, calcification, and complications.
      Intake of large amounts of alcohol (> or = 50 g/d) reduced time to calcification
      and death.

PMID- 11243271
TI  - Association of atrial fibrillation and aortic atherosclerosis: a population-based
      study.
AB  - OBJECTIVE: To examine the association between atrial fibrillation (AF) and aortic
      atherosclerosis in the general population. SUBJECTS AND METHODS: Transesophageal
      echocardiography was performed in 581 subjects, a random sample of the adult
      Olmsted County, Minnesota, population (45 years of age or older) participating in
      the Stroke Prevention: Assessment of Risk in a Community (SPARC) study. The
      frequency of aortic atherosclerosis was determined in 42 subjects with AF and
      compared with that in 539 subjects without AF (non-AF group). RESULTS: Subjects
      with AF were significantly older than non-AF subjects (mean +/- SD age, 82+/-10
      vs 66+/-13 years, respectively; P<.001) and more commonly had hypertension (28
      [66.7%] vs 288 [53.4%], respectively; P=.10). The 2 groups were similar in sex
      and frequency of diabetes mellitus, hyperlipidemia, or smoking history (P>.10).
      The odds of aortic atherosclerosis (of any degree) were 2.87 times greater (95%
      confidence interval [CI], 1.41-5.83; P=.004) and the odds of complex
      atherosclerosis (protruding atheroma >4 mm thick, mobile debris, or plaque
      ulceration) were 2.71 times greater (CI, 1.13-6.53; P=.03) in the AF group than
      in the non-AF group. Age was a significant predictor of aortic atherosclerosis
      (P<.001). After adjusting for age, the odds of atherosclerosis and complex
      atherosclerosis were not significantly different between the 2 groups (P=.13 and
      P=.75, respectively). CONCLUSIONS: In the general population, AF is associated
      with aortic atherosclerosis, including complex atherosclerosis. This association
      is related to age since both AF and aortic atherosclerosis are more frequent in
      the elderly population.

PMID- 11243272
TI  - Efficacy and safety of intravenous phytonadione (vitamin K1) in patients on long
      term oral anticoagulant therapy.
AB  - OBJECTIVES: To determine the safety and efficacy of intravenously administered
      phytonadione (vitamin K1) in patients on routine oral warfarin anticoagulation.
      PATIENTS AND METHODS: This retrospective cohort study comprised adults who were
      taking warfarin, were not bleeding, and received intravenous phytonadione
      anticoagulation therapy before a diagnostic or therapeutic procedure between
      September 1, 1994, and March 31, 1996. The main outcome measures were adverse
      reactions to intravenously administered phytonadione, prothrombin-international
      normalized ratio time values, the incidence of bleeding and thrombosis after the
      procedure, and the time between the procedure and return to anticoagulation after
      resumption of warfarin treatment. RESULTS: Two (1.9%) of the 105 patients studied
      had suspected adverse reactions to intravenous phytonadione (dyspnea and chest
      tightness during infusion in both). For the 82 patients who underwent a
      procedure, the median time from phytonadione to procedure onset was 27 hours
      (range, 0.7-147 hours), which was significantly less for patients receiving an
      initial phytonadione dose of more than 1 mg (P=.009). None had thromboembolism
      after surgery, although 2 (2.4%) of the 82 patients had procedure-associated
      major bleeding. For the 60 patients resuming warfarin therapy after a procedure,
      the median time to return to therapeutic anticoagulation was 4.1 days (range, 0.8
      31.7 days) and was unaffected by the phytonadione dosage. CONCLUSIONS:
      Intravenous phytonadione appears to be safe and is effective for semiurgent
      correction of long-term oral anticoagulation therapy before surgery. In small
      doses, it does not prolong the patient's time to return to therapeutic
      anticoagulation.

PMID- 11243273
TI  - Tactile illusion perception in patients with central pain.
AB  - OBJECTIVE: To evaluate lemniscal pathways in patients with central pain (CP) by
      use of a novel tactile illusion (TI)-producing technique. PATIENTS AND METHODS:
      Somatosensory (SS) and TI testing was performed on the unaffected and affected
      wrists of 27 patients with unilateral central nervous system injury and
      unilateral CP. Data on TI testing-naive control subjects were used to adjust for
      a learning effect. RESULTS: Testing in CP patients with cervical and brainstem
      injuries revealed predominantly unchanged or decreased SS perception on the
      affected side compared with the unaffected side. The majority of cervical- and
      brainstem-injured subjects with CP had improved TI performance on the affected
      side compared with the unaffected side. All the thalamic-injured and most of the
      suprathalamic-injured CP patients had altered SS testing with either decreased or
      increased SS perception noted. In these same CP patients the majority had reduced
      TI perception on the affected side compared with the unaffected side.
      Unexpectedly, perseveration of numbers was noted in patients with Dejerine-Roussy
      syndrome, and expanded TI testing was performed to better define this
      observation. CONCLUSION: Cervical spinal cord-injured CP patients may have
      improved TI perception, whereas the majority of patients with supraspinal
      injuries and CP have reduced SS and TI perception. A unique sensory phenomenon of
      TI perseveration was observed in some patients with Dejerine-Roussy syndrome.

PMID- 11243274
TI  - A preliminary analysis of psychophysiological variables and nursing performance
      in situations of increasing criticality.
AB  - OBJECTIVE: To examine the relationship between psychological, physiological, and
      performance variables in intensive care unit (ICU) nurses in situations of
      increasing criticality. SUBJECTS AND METHODS: Psychophysiological variables and
      endotracheal suctioning performance were examined in a classroom, a skills
      laboratory, and an ICU. Situation-specific anxiety (state anxiety) and the
      predisposition to view situations as threatening (trait anxiety), cognitive
      appraisal, and heart rate were measured and compared with self-appraisal and a
      nurse instructor's ratings of suctioning performance. Baseline data were obtained
      during class on 45 novice ICU nurses. RESULTS: Twenty-six nurses provided
      complete data, which included being videotaped and monitored in the classroom, in
      the skills laboratory performing endotracheal suctioning, and in the ICU during
      suctioning. High state anxiety significantly predicted poor ICU suctioning
      performance (P<.04). Nurses high in state and trait anxiety, worry, and heart
      rate performed poorly compared with less anxious nurses. Nurses in this study who
      performed best had a mean heart rate of 94 beats/min. CONCLUSION: Those nurses
      who are high state anxious, high trait anxious, and worried and who had a faster
      heart rate performed less well than their more relaxed peers. Nurses with high
      state anxiety may be at risk for attrition, burnout, medical errors, and poor
      performance in other ICU nursing tasks.

PMID- 11243275
TI  - Hereditary red blood cell disorders in middle eastern patients.
AB  - Hereditary disorders of erythrocytes are common in many areas of the world,
      including the Middle East. In some regions of the Middle East more than 10% of
      the population are carriers of a gene for one of these conditions. When patients
      from the Middle East seek medical care in the West, an unrecognized but
      clinically important erythrocyte disorder can result in serious complications
      during routine medical care, such as a drug-induced hemolytic crisis. This
      article reviews the most important and most common inherited red blood cell
      disorders in Middle Eastern patients, including glucose-6-phosphate dehydrogenase
      deficiency, the thalassemias, and sickle cell disorders. We discuss when to
      suspect such conditions, how to determine their presence, and how to avoid
      potential complications related to them. Although a detailed discussion of
      treatment of erythrocyte disorders is beyond the scope of this article, some
      general management principles are described.

PMID- 11243276
TI  - Medical care of elderly patients with hip fractures.
AB  - Medical morbidity associated with hip fractures in the elderly population is
      considerable. The all-cause mortality rate is 24% at 12 months. The functional
      limitations of survivors can be pronounced. As the American population ages, hip
      fractures will substantially affect the utilization of hospital resources.
      Several issues, including preoperative clearance and related surgical timing,
      deep venous thrombosis prophylaxis, delirium, nutrition, and urinary tract
      management, are important in the care of these patients. A close partnership
      between orthopedic surgeons and clinicians provides the best strategy of care for
      the subset of patients with multisystemic complications.

PMID- 11243277
TI  - Pharmacogenomics: a clinician's primer on emerging technologies for improved
      patient care.
AB  - Pharmacogenomics is a term recently coined to embody the concept of
      individualized and rational drug selection based on the genotype of a particular
      patient. Customization of drug therapy offers the potential for optimal safety
      and efficacy in an individual patient. Such a process contrasts current
      prescribing practices, which use medications shown to be safe and effective in
      patient populations or based on anecdotal experiences. Within patient
      populations, medications vary in their efficacy among individual patients. More
      importantly, a medication that is safe and effective in one patient may be
      ineffective or even harmful in another. Underlying many of these phenotypic
      differences are genotypic variants (polymorphisms) of key enzymes and proteins
      that affect the safety and efficacy of a drug in an individual patient. An
      understanding of these polymorphisms has the potential to enhance patient care by
      allowing physicians to customize the selection of medication to meet individual
      patient needs. Pharmacogenomics may also lead to improved compliance and shorter
      time to optimal disease management, thereby reducing morbidity and mortality.
      Significant cost savings could result from reductions in polypharmacy as well as
      from fewer physician encounters and hospitalizations for exacerbations of
      underlying illness and because of adverse drug reactions.

PMID- 11243278
TI  - 59-year-old man with pelvic pain and hypergammaglobulinemia.

PMID- 11243279
TI  - Pellagra in 2 homeless men.
AB  - Pellagra is a nutritional disease with cutaneous, gastrointestinal, and
      neuropsychiatric manifestations. Because of the diversity of pellagra's signs and
      symptoms, diagnosis is difficult without an appropriate index of suspicion.
      Untreated, pellagra is fatal. Two cases of pellagra in contemporary homeless
      people are described. Complete evaluation supported a clinical diagnosis of
      pellagra after exclusion of other possibilities. Signs and symptoms resolved
      after institution of niacin therapy and change in diet. Appropriate suspicion for
      a diagnosis of pellagra requires attention to a combination of socioeconomic and
      behavioral risk factors for nutritional deficiency. The combination of
      homelessness, alcohol abuse, and failure to eat regularly--particularly, failure
      to make use of shelter-based meal programs--may identify people at special risk
      in contemporary settings.

PMID- 11243280
TI  - Multiple aortic thrombi associated with protein C and S deficiency.
AB  - We describe a woman with an unusual case of thromboembolism of the mesenteric
      artery in whom multiple thrombi were subsequently found in the aorta and right
      heart chambers on transesophageal echocardiography. Further evaluation revealed a
      deficiency of protein C and S plasma proteins, inhibitors of the clotting system.
      The patient was treated successfully with systemic anticoagulation. Aortic
      thrombus is common in the setting of underlying atherosclerosis. However, the
      association of aortic thrombus with a deficiency of protein C and S is rare. To
      our knowledge, this is the first reported case of mural thrombus of the thoracic
      aorta associated with combined protein C and S deficiency. Our report underscores
      the important role of transesophageal echocardiography in the evaluation of
      patients with arterial thromboembolism.

PMID- 11243281
TI  - Acute myocardial infarction associated with amphetamine use.
AB  - Myocardial infarction is a rarely reported complication of amphetamine use. We
      report the case of a healthy 31-year-old man who presented to our emergency
      department with no clinical evidence of an acute coronary event after intravenous
      injection of amphetamines. However, he subsequently experienced a non-Q-wave
      anterior wall myocardial infarction associated with the use of amphetamines.

PMID- 11243282
TI  - Paraneoplastic and metastatic neurologic complications of Merkel cell carcinoma.
AB  - Merkel cell carcinoma is a rare primary cutaneous neuroendocrine tumor that is
      locally aggressive and frequently accompanied by distant metastases. Neurologic
      complications of Merkel cell carcinoma are rare. We describe a 69-year-old man
      who presented with Lambert-Eaton myasthenic syndrome and was found to have Merkel
      cell carcinoma. The paraneoplastic syndrome improved with initial treatment of
      the malignancy. He subsequently developed a solitary brain metastasis and died of
      leptomeningeal carcinomatosis.

PMID- 11243283
TI  - Short segment Barrett esophagus and specialized columnar mucosa at the
      gastroesophageal junction.
AB  - The rising incidence of adenocarcinoma of the esophagus and the gastric cardia
      has generated interest in the finding of intestinal metaplasia or specialized
      columnar mucosa in this location. Short segment Barrett esophagus is defined by
      the presence of columnar-appearing mucosa in the distal esophagus (<3 cm in
      length) with intestinal metaplasia on biopsy. In contrast, intestinal metaplasia
      may also be present if biopsy specimens are obtained from a normal-appearing
      squamocolumnar junction or from the gastric cardia (ie, immediately below the
      gastroesophageal junction) in the absence of columnar lining of the distal
      esophagus. This has been termed cardia intestinal metaplasia, gastroesophageal
      junction intestinal metaplasia, or specialized columnar mucosa at the
      gastroesophageal junction. This article reviews the currently available data on
      these rapidly evolving entities of short segment Barrett esophagus and
      specialized columnar mucosa at the gastroesophageal junction.

PMID- 11243285
TI  - Dr Henry S. Plummer and the 1928 Plummer building.

PMID- 11243284
TI  - Rationale for surgical therapy of Barrett esophagus.
AB  - Barrett esophagus has malignant potential and seems to be an acquired
      abnormality. It is associated with chronic gastroesophageal reflux disease and
      represents its severest form. The literature comparing medical treatment with
      antireflux surgery was reviewed. Questions regarding the advantages of surgery,
      who should undergo surgery, whether surgery can change the course of Barrett
      esophagus, the change in cancer risk, who needs surveillance, and cost
      effectiveness were addressed. The incidence of developing Barrett cancer was 1 in
      145 patient-years in reviewing 2032 patient-years of medical therapy compared
      with 1 in 294 patient-years in reviewing 4122 patient-years after surgery. Median
      follow-up time in the 2 groups was 2.7 years in the medically treated patients
      and 4.0 years in the surgically treated patients. Surveillance of Barrett
      esophagus is required irrespective of treatment. Laparoscopic antireflux surgery
      was found to be cost-effective after 7 years. Although these data do not prove
      that surgery is superior to medical treatment in the prevention of cancer related
      to Barrett esophagus, we found a tendency for surgery to be better than medical
      therapy to prevent the development and progression of Barrett carcinoma.

PMID- 11243286
TI  - Images and reflections from Mayo Clinic heritage.

PMID- 11243287
TI  - Impact of FDA advisory on reported vacuum-assisted delivery and morbidity.
AB  - OBJECTIVE: In May 1998 the US Food and Drug Administration (FDA) issued a health
      advisory reporting neonatal injuries/deaths following vacuum delivery and
      encouraged voluntary reports of future adverse events. We compared FDA reports of
      vacuum delivery adverse events prior to and following the advisory. METHODS: The
      FDA database (MAUDE) was searched for vacuum deliveries using brand name,
      manufacturer name, and procedure "string searches." Cases were sorted by report
      date, source, and manufacturer. Neonatal morbidity was quantified as deaths and
      life-threatening or nonlife-threatening events. RESULTS: A total of 80 reported
      adverse cases were identified after duplicate cases were consolidated. Twenty
      five were reported to the FDA prior to the 1998 advisory and 55 in the immediate
      6-month period following the advisory. There was a 22-fold increase in reported
      events from five events/year prior to the advisory to an estimated 110
      events/year following the advisory. The distribution of reporting sources changed
      significantly following the advisory with increased "manufacturer" (8-43%) and
      decreased "voluntary" reports (56-20%). All major brand names were represented.
      During the 6 months following the FDA advisory there were 10 neonatal deaths, 30
      life-threatening events, 12 nonlife-threatening events, and three equipment
      related reports. Infant deaths were due to intracranial or subgaleal hematomas.
      Injuries included skull fracture, scalp abrasions, and cephalohematomas.
      CONCLUSIONS: The FDA advisory was associated with a 22-fold increase in the rate
      of reported adverse events. This increase in reporting likely represents both
      enhanced awareness of complications as well as an increase in vacuum-related
      adverse neonatal sequelae. As vacuum delivery is associated with greater neonatal
      morbidity/ mortality than was previously recognized, the adage that the vacuum is
      "designed to come off before infant damage occurs" appears unsubstantiated. It is
      recommended that manufacturers quantify the suction and traction capabilities of
      present and new proposed vacuum cup designs.

PMID- 11243288
TI  - Umbilical vein white blood cell count as a marker of acidemia in term neonates.
AB  - OBJECTIVE: White blood cells are mobilized under both hypoxic and infectious
      conditions. Intrauterine hypoxia is linked to increased risk of cerebral palsy
      and is potentiated by the presence of infection. We hypothesized that umbilical
      vein white blood cell elevation in term neonates is associated with intrauterine
      acidemia. METHODS: We prospectively evaluated all liveborn neonates delivered at
      our institution for a 6-month period. Umbilical arterial blood was analyzed for
      pH and blood gas and venous blood for hematologic indices. Medical records of
      cases greater than or equal to 37 weeks' gestation were reviewed for correlative
      data. Student's t-test was used to determine difference of means and Chi-square
      test for goodness of fit. Pearson coefficients of correlation were applied where
      appropriate. RESULTS: A total of 1,948 liveborn, term neonates were delivered
      during the study period; 1,561 cases had white blood cell analysis and arterial
      blood gas data available. Acidemic cases had higher white blood cell (15.0 vs.
      12.4 cells x 10(3)/mm3, P < 0.001), lymphocyte (4.43 vs. 3.59 cells X 10(3)/mm3,
      P < 0.0001), and neutrophil counts (9.08 vs. 7.71 cells x 10(3)/mm3, P < 0.01).
      As umbilical artery pH decreased, white blood cells became more prevalent.
      Likewise, as base deficit deepened, white blood cell counts increased.
      CONCLUSIONS: This study demonstrates an association between deepening acidemia
      and increasing white blood cell, lymphocyte, and neutrophil counts. Although
      statistically different, mean white blood cell counts for acidemic and
      nonacidemic cases are fairly close, limiting the clinical applicability in
      determining whether pathology is present in an individual case.

PMID- 11243289
TI  - Color flow mapping for myometrial invasion in women with a prior cesarean
      delivery.
AB  - OBJECTIVES: Our aim was to evaluate the utility of color flow mapping in the
      prediction of placental myometrial invasion in women with Cesarean delivery.
      METHODS: Ultrasound color flow mapping was performed on placental implantations
      in potential proximity to the hysterotomy scar. The smallest myometrial thickness
      was measured under the placenta to evaluate the degree of myometrial attenuation
      in this area and note was made of unusual vascular lakes. RESULTS: Two hundred
      fifteen women with placentas in proximity to the prior hysterotomy scar underwent
      color Doppler mapping. Of 20 women with placenta previa and Cesarean delivery, 15
      had Cesarean hysterectomy for bleeding complications and nine had the
      pathological diagnosis of placental invasion. The measurement of <1 mm for the
      smallest myometrial thickness or presence of large intraplacental lakes was
      predictive of myometrial invasion (sensitivity 100%, specificity 72%, PPPV 72%,
      and NPV 100%). CONCLUSIONS: Color flow mapping predicted myometrial invasion when
      the smallest myometrial thickness was <1 mm and large intraplacental lakes were
      demonstrated.

PMID- 11243291
TI  - Short cervix: a cause of preterm delivery in young adolescents?
AB  - OBJECTIVE: To test the hypothesis that at midgestation younger adolescents (<16
      years of age at conception) have shorter cervices than older adolescents (16-19
      years of age at conception). METHODS: At midgestation (22.9 +/- 2.4 weeks) we
      measured cervical length by transvaginal ultrasound in a group of 46 13-19-year
      old participants in an intensive, adolescent-oriented, antenatal program.
      Subjects were also comprehensively screened and treated for other recognized
      physiologic, microbiologic, obstetric, behavioral, and psychosocial factors
      associated with preterm delivery. Univariate, bivariate, and logistic regression
      analyses were used. RESULTS: The 18 younger adolescents had significantly shorter
      cervices than the 28 older adolescents (30 +/- 11 mm vs. 39 +/- 8 mm; P = 0.002).
      The younger adolescents' cervices were also more likely to be < or =25 mm long
      (33% and 4%, respectively; P = 0.02) and to exhibit funneling (39% vs. 4%; P =
      0.01). Teenagers with cervices < or =25 mm long were younger, thinner, more apt
      to report vaginal bleeding and substance abuse, and to be treated for preterm
      labor (71% vs. 21%; P = 0.005). Logistic regression analyses revealed that age
      <16 years at conception (odds ratio = 13.7; 95% CI: 1.3-151.4) and substance
      abuse (odds ratio = 8.5; 95% CI: 1.2-62.8) were associated with cervical length <
      or =25 mm. Cervical length < or =25 mm was the only significant predictor of
      preterm delivery (odds ratio = 26.2; 95% CI: 2.1-333.6; P = 0.01) in this
      population of adolescents who were routinely treated for other recognized causes
      of preterm delivery. CONCLUSIONS: Cervical length < or =25 mm and cervical
      funneling may be complications of conception prior to 16 years of age. Randomized
      trials are needed to determine if younger adolescents benefit preferentially from
      ultrasound screening for short cervix at midgestation.

PMID- 11243290
TI  - Will cervicovaginal interleukin-6 combined with fetal fibronectin testing improve
      the prediction of preterm delivery?
AB  - OBJECTIVE: We sought to investigate if determination of cervicovaginal
      interleukin-6 (IL-6) levels would enhance the positive predictive value of fetal
      fibronectin (fFN) for preterm birth. METHODS: A prospective cohort study was
      undertaken of 135 women between 24 and 34 weeks gestation with symptoms of
      suspected preterm labor. Cervicovaginal secretions were collected for both IL-6
      and fFN and measured by immunoassay and ELISA, respectively. Outcome variables
      included preterm delivery in less than 48 h, within 7 days, and prior to 37
      weeks. Statistical analysis was performed with Fisher's exact test, regression
      for logarithmic transform levels, and multivariate logistic regression. ROC
      curves were created for IL-6 levels. RESULTS: IL-6 and fFN levels were both
      elevated in cervicovaginal secretions of women with symptoms of preterm labor. IL
      6 values >100 pg/ml resulted in a odds ratio for delivery at <37 weeks of 1.57
      (95%CI=0.89-2.75, P=.11), whereas fFN values >50 ng/ml resulted in a preterm
      delivery risk of 4.58 (95%CI=1.54-13.35, P=.003). Combining IL-6 and fFN results
      did not improve upon the predictive value of fFN alone for preterm birth [odds
      ratio 4.00 (95%CI=1.31-12.17, P=.015)]. CONCLUSION: Cervicovaginal IL-6 levels
      did not provide any additional, independent effect on the prediction of preterm
      birth beyond that of fFN testing alone.

PMID- 11243292
TI  - Antibiotic prophylaxis at Cesarean delivery.
AB  - OBJECTIVE: Our aim was to compare the efficacy of ampicillin, cefotetan, and
      ampicillin/sulbactam in the prevention of post-Cesarean endomyometritis. METHODS:
      Consenting patients undergoing Cesarean delivery at the University of Louisville
      Hospital were enrolled in a prospective, double-blinded randomization to receive
      either ampicillin/sulbactam (Group 1), cefotetan (Group 2), or ampicillin (Group
      3) single dose antibiotic prophylaxis following umbilical cord clamping. The
      primary outcome variable was the frequency of endomyometritis in the respective
      groups. RESULTS: Among 301 randomized patients, outcome data was available for
      298 patients. Fourteen patients (4.7%), all of whom underwent non-elective
      Cesarean delivery, developed endomyometritis. The frequency of endomyometritis
      was not different among groups: Group 1, 4/101 (4%); Group 2, 4/96 (4.2%); and
      Group 3, 6/101 (5.9%). Wound infections were infrequently observed 4/298 (1.3%)
      without significant differences among groups. Stepwise discriminative analysis
      identified only last cervical dilatation as a significant predictor of
      endomyometritis (P = 0.006). CONCLUSION: Post-Cesarean endomyometritis occurs
      infrequently following single dose antibiotic prophylaxis after umbilical cord
      clamping. An advantage of broader spectrum antibiotics over ampicillin was not
      demonstrated.

PMID- 11243293
TI  - Effects of lipopolysaccharide on interleukin-6 production in perfused human
      placental cotyledons.
AB  - OBJECTIVE: To determine if lipopolysaccharide (LPS) alters production of
      interleukin-6 (IL-6) or vascular tone in perfused placental cotyledons. METHODS:
      Control and study cotyledons from nine placentas were perfused for 3 h. Study
      cotyledons received LPS in concentrations of 0.01 mcg/ml (n = 3), 0.1 mcg/ml (n =
      3), or 1.0 mcg/ml (n = 3). Effluents were collected at 30, 60, 120, and 180 min
      following infusion with LPS. IL-6 concentrations were measured by enzyme-linked
      immunosorbant assay. Perfusion pressures were recorded at 10-min intervals. Data
      were analyzed using ANOVA for repeated measures. RESULTS: IL-6 production
      significantly increased over time in both the study and control cotyledons (P =
      0.002). LPS treatment did not affect IL-6 production (P = 0.85) and there were no
      observable dose effects (P = 0.13). Perfusion pressures did not differ (P =
      0.16). CONCLUSIONS: The isolated perfused placental cotyledon produces IL-6 and
      concentrations increase over time. LPS does not alter production of IL-6 or
      fetoplacental vascular tone.

PMID- 11243294
TI  - Dilatation of the left renal vein in preeclampsia.
AB  - OBJECTIVE: Our purpose was to compare the morphological changes in renal veins
      during normal pregnancy and pregnancy involving preeclampsia. METHODS: We used
      ultrasonography to measure maximum diameters of the right and left renal veins,
      and the diameter of the left renal vein where it crosses the abdominal aorta in
      normal pregnancy and preeclampsia. RESULTS: In women with normal pregnancy, the
      maximum diameter of the left renal vein was 5.5 +/- 1.9 mm in the 1st trimester,
      5.8 +/- 1.6 mm in the 2nd trimester, and 6.4 +/- 1.4 mm in the 3rd trimester. The
      diameter of the left renal vein where it crosses the abdominal aorta was 3.3 +/-
      1.1 mm in the 1st trimester, 4.1 +/- 1.3 mm in the 2nd trimester, and 4.0 +/- 0.9
      mm in the 3rd trimester. In contrast, the maximum diameter of the left renal vein
      in women that had preeclampsia with onset in the 2nd trimester was 9.8 +/- 2.4 mm
      and that in women whose preeclampsia began in the 3rd trimester was 8.7 +/- 1.6
      mm. The diameter of the left renal vein in preeclampsia was significantly larger
      than that in normal pregnancy (P < 0.05). There were no significant differences
      between normal pregnancy and preeclampsia in the maximum diameter of the right
      renal vein or that of the left renal vein where it crosses the abdominal aorta.
      CONCLUSIONS: In preeclamptic women, a dilatation of the left renal vein was
      observed. This suggests that the relative constriction and congestion of the left
      renal vein takes part in the pathophysiology of preeclampsia. Measurement of the
      diameter of the left renal vein would provide a simple, cost-effective tool for
      the diagnosis of preeclampsia.

PMID- 11243295
TI  - Artifactual fetal electrocardiographic detection using internal monitoring
      following intrapartum fetal demise during VBAC trial.
AB  - Absent or erratic fetal electrocardiographic signal can result in artifactual
      electronic fetal heart rate recording. We report a case where detection of
      maternal heart rate through internal fetal scalp monitor may have masked
      intrauterine fetal demise secondary to acute uterine rupture during a VBAC trial.

PMID- 11243296
TI  - Late second stage rupture of the uterus and bladder with vaginal birth after
      cesarean section: a case report and review of the literature.
AB  - Rupture of a uterine scar during labor with concomitant severe injury to the
      maternal bladder has been reported sporadically. Previously reported cases have
      been diagnosed under a variety of conditions, commonly at the time of repeat
      Cesarean delivery. A case of maternal bladder rupture diagnosed following forceps
      assisted vaginal delivery after Cesarean is presented. Severe bradycardia
      developed suddenly in the second stage of labor. Rupture of the uterine scar was
      diagnosed after sudden onset of severe lower abdominal pain with delivery of the
      placenta. At laparotomy, extensive injury to the bladder was found and successful
      repair of both injuries was performed. A review of previously reported similar
      cases with their mechanism of injury and presentation is presented. Serious
      maternal bladder injury at the time of uterine rupture remains a risk of
      attempted vaginal delivery after prior Cesarean section.

PMID- 11243297
TI  - Recurrent fetal cystic hygroma with normal chromosomes: case report and review of
      the literature.
AB  - Recurrence of fetal cystic hygroma in subsequent pregnancies is extremely rare. A
      review of the literature to date revealed only two other reports of recurrence
      with normal fetal karyotypes documented in at least two of the affected
      pregnancies. At 11 weeks' gestation, the fetus of a 19-year-old gravida 3 para 0
      was discovered to have a large cystic hygroma. Subsequent evaluation during the
      second trimester revealed increasing size of the septated nuchal mass and
      ascites. A 46,XX fetal karyotype was noted in her two prior pregnancies, both of
      which had also been complicated by the development of cystic hygroma and
      nonimmune hydrops. Cystic hygroma, associated with a normal karyotype, can be
      inherited as an autosomal recessive trait.

PMID- 11243298
TI  - Second trimester low-lying placenta and in-vitro fertilization? Exclude vasa
      previa.
AB  - We report the prenatal diagnosis of vasa previa using transvaginal sonography and
      color Doppler. This case supports the previously reported association of vasa
      previa with second trimester low-lying placentas and in-vitro fertilization.
      Sonographic examination for vasa previa should be considered in pregnancies with
      low-lying placentas and those resulting from in-vitro fertilization.

PMID- 11243299
TI  - Malignant pleural mesothelioma in pregnancy.
AB  - A 37-year-old pregnant woman presented at 18 weeks' gestation with unrelenting
      chest and shoulder pain, massive pleural effusion, and a large thoracic mass.
      Biopsy revealed an undifferentiated sarcomatous pleural mesothelioma. Malignant
      mesothelioma is a rare thoracic malignancy, which has not been described in
      pregnancy and appears to be minimally affected by the pregnant state.

PMID- 11243300
TI  - Diastolic dysfunction precedes myocardial hypertrophy in the development of
      hypertension.
AB  - BACKGROUND: Left ventricular (LV) hypertrophy and impaired diastolic function may
      occur early in systemic hypertension, but longitudinal studies are missing.
      METHODS: We performed an echocardiographic follow-up study in young initially
      normotensive male offspring of hypertensive (OHyp) (n = 25) and normotensive
      (ONorm) (n = 17) parents. Blood pressure (BP), LV mass, and mitral inflow were
      determined at baseline and after 5 years. Pulmonary vein flow pattern assessment
      and septal myocardial Doppler imaging were additionally performed at follow-up.
      RESULTS: At follow-up, BP was not significantly different between the two groups
      (128 +/- 11/84 +/- 10 v 123 +/- 11/81 +/- 5 mm Hg, OHyp v ONorm) but five OHyp
      had developed mild hypertension. LV mass index remained unchanged and was not
      different between the two groups at follow-up (92 +/- 17 v 92 +/- 14 g/m2).
      Diastolic echocardiographic properties were similar at baseline, but, at follow
      up, the following differences were found: mitral E deceleration time (209 +/- 32
      v 185 +/- 36 msec, P < .05) and pulmonary vein reverse A wave duration (121 +/-
      15 v 107 +/- 12 msec, P < .05) were prolonged in the OHyp as compared to the
      ONorm. Compared to the normotensive subjects, the five OHyp who developed
      hypertension had more pronounced alterations of LV diastolic function, that is,
      significantly higher mitral A (54 +/- 7 v 44 +/- 9 cm/sec, hypertensives v
      normotensives, P < .05), lower E/A ratio (1.31 +/- 0.14 v 1.82 +/- 0.48, P <
      .05), increased systolic-to-diastolic pulmonary vein flow ratio (1.11 +/- 0.3 v
      0.81 +/- 0.16, P < .005), longer myocardial isovolumic relaxation time (57 +/- 7
      v 46 +/- 12 msec, P < .05) as well as smaller myocardial E (10 +/- 1 v 13 +/- 2
      cm/sec, P < .05) and E/A ratio (1.29 +/- 0.25 v 1.78 +/- 0.43, P < .05), despite
      similar LV mass (91 +/- 16 v 93 +/- 18 g/m2). CONCLUSIONS: Over a 5-year follow
      up, initially lean, normotensive, young men with a moderate genetic risk for
      hypertension, developed Doppler echocardiographic alterations of LV diastolic
      function compared to matched offspring of normotensive parents. These alterations
      were more pronounced in the OHyp who developed mild hypertension and occurred
      without a distinct rise in LV mass.

PMID- 11243301
TI  - Plasma leptin concentration, insulin sensitivity, and 24-hour ambulatory blood
      pressure and left ventricular geometry.
AB  - Left ventricular (LV) hypertrophy is an important predictor of cardiovascular
      morbidity and mortality. Hemodynamic factors, such as 24-h blood pressure (BP)
      values, are responsible for left ventricular hypertrophy in hypertensives. On the
      other hand, some metabolic factors have also been suggested to affect LV mass and
      geometry. In particular, plasma leptin concentrations have been found associated
      to LV myocardial growth. Because chronic leptin infusion stimulates sympathetic
      nervous system activity and increases BP levels, the role of 24-h BP values on
      leptin-related changes in myocardial wall geometry cannot be ruled out. Thus, the
      aim of our study was to evaluate whether the relationship between plasma leptin
      levels and LV wall thickness is mediated by 24-h BP values in hypertensive male
      patients. Thirty-six newly diagnosed hypertensive patients underwent Doppler
      echocardiographic examination, 24-h ambulatory BP recording, and metabolic
      (euglycemic hyperinsulinemic glucose clamp and fasting plasma leptin levels)
      measurements. Left ventricular mass correlated positively only with ambulatory
      diastolic BP (DBP) values, whereas the indices of myocardial wall growth such as
      interventricular septum thickness and sum of wall thickness (ie, septal +
      posterior wall thickness) correlated either with 24 h, daytime, or nighttime DBP,
      as well as with fasting plasma glucose, fasting plasma leptin, and insulin action
      after adjustment for age, body mass index (BMI), and waist/hip ratio (WHR). In
      contrast, plasma leptin concentration did not correlate with clinical and
      ambulatory BP values. A multiple linear regression analysis allowed to
      investigate the independent role of main anthropometric and cardiovascular
      covariates on the sum of wall thickness variability. A model that includes age,
      BMI, WHR, fasting plasma leptin concentration, plasma Na+ concentration, insulin
      action, and nighttime DBP explained 68% of the sum of wall thickness variability.
      In such a model, plasma leptin concentration (P < .001), insulin action (P <
      .029), and nighttime DBP (P < .002) were significantly and independently
      associated with myocardial wall thickness. In conclusion, our study demonstrates
      that in hypertensive men fasting plasma leptin levels are determinant of
      myocardial wall thickness independently of 24-h BP values.

PMID- 11243302
TI  - Effect of familial hypertension on glomerular hemodynamics and tubulo-glomerular
      feedback after uninephrectomy.
AB  - Familial hypertension, glomerular hemodynamic alterations, and dysregulation of
      tubulo-glomerular feedback (TGFB) have all been associated with the development
      of chronic renal failure. In the present study we evaluated renal and glomerular
      hemodynamics and TGFB responses in healthy kidney donors either with or without
      familial hypertension, before and after nephrectomy. Para-amino-hippurate plasma
      clearance (CPAH) and inulin plasma clearance (CInu) were measured in 15 kidney
      donors before and 1 year after nephrectomy. All subjects were normotensive and
      were kept in a sodium-replete state. Both clearances were measured after 40 min
      of constant infusion of PAH and Inu, as well as 20, 30, 50, and 60 min after the
      intravenous administration of acetazolamide (5 mg/kg). Glomerular hemodynamics
      were calculated by means of the Gomez formulae. Nephrectomy caused the expected
      decreases in CPAH and CInu and increase in the filtration fraction (all P <
      .0001). The decrease in renal resistances of the remaining kidney was greater at
      the afferent (-24%, P = .0075) than at the efferent arteriolar level (-17%, P <
      .0001). The TGFB activation was not altered by nephrectomy or by familial
      hypertension. Effective renal plasma flow (ERPF) decrease after TGFB activation
      appeared earlier than glomerular filtration rate (GFR) decrease before (P = .01),
      but not after, nephrectomy (P = .48). The presence of familial hypertension was
      associated with increased glomerular pressure (P = .0004). This study suggests
      that uninephrectomy in healthy human subjects causes a greater decrease in
      afferent arteriolar resistances, but that TGFB responses are not quantitatively
      altered. Familial hypertension is associated with a tendency toward higher
      glomerular pressures.

PMID- 11243303
TI  - Comparison of candesartan versus enalapril in essential hypertension. Italian
      Candesartan Study Group.
AB  - BACKGROUND: The objective of this study was to compare the antihypertensive
      efficacy and tolerability of candesartan cilexetil (CC) with that of enalapril
      (E) and placebo (P) in hypertensives by clinic and ambulatory blood pressure
      (BP). PROCEDURES: The study was an Italian multicenter, randomized, double-blind,
      parallel group trial including 227 mild to moderate essential hypertensives (age
      range, 18 to 70 years). After 4 weeks of P, patients were randomized to 8 weeks
      of treatment with P or CC (4 mg) or E (10 mg) once daily, which was eventually
      increased to 8 mg and 20 mg once daily in nonresponders. At the end of each study
      phase, trough BP was measured by conventional sphygmomanometry and ambulatory BP
      was monitored over 24 h by a Spacelabs device. Analysis of 24-h BP profile
      included calculation of 24-h, daytime, nighttime, and hourly average values.
      RESULTS: In the 178 patients evaluable per protocol, at the end of 8 weeks of
      treatment, trough systolic (S) and diastolic (D) BP were similarly reduced by
      both active treatments (13 +/- 12 and 10 +/- 7 mm Hg for CC and 14 +/- 12 and 10
      +/- 7 mm Hg for E) and significantly more by both treatments than by P (6 +/- 11
      and 7 +/- 8 mm Hg, P < .01 v CC and E). In the 85 patients with valid 24-h
      recordings reduction in 24-h BP was again similar for the two active groups. The
      antihypertensive effect was still evident during h 23 and 24 after the last dose
      for both active treatments (8 +/- 20 v 5 +/- 18 mm Hg for SBP and 4 +/- 12 v 6 +/
      13 mm Hg for DBP, CC v E, respectively) but not for P. Heart rate was not
      significantly modified by either active treatment. The incidence of adverse
      events was greater in the E than in the CC group. CONCLUSIONS: Our study provides
      evidence that CC at a dose of 4 to 8 mg is as effective as E at a dose of 10 to
      20 mg over 24 h, but is better tolerated than E.

PMID- 11243304
TI  - Obesity, leptin and blood pressure among children in Taiwan: the Taipei
      Children's Heart Study.
AB  - BACKGROUND: Obesity is associated with the occurrence of hypertension; however,
      the mechanisms of obesity-induced high blood pressure (BP) remain unclear.
      Leptin, the obese (ob) gene product, is associated with the occurrence of obesity
      and related disorders in humans. The purpose of this study was to evaluate the
      association between plasma leptin and BP among children. METHODS: After
      multistage sampling, we randomly selected 1265 children (618 boys and 647 girls)
      with a mean age of 13.3 years (12 to 16 years old) in this cross-sectional
      survey. Obesity measurements included body mass index (BMI) and waist-to-hip
      circumference ratio (WHR). Plasma leptin levels were measured by
      radioimmunoassay. RESULTS: The mean and median plasma leptin levels were 4.1 and
      2.4 ng/mL among boys and 10.1 and 8.8 ng/mL among girls. Children in the highest
      quintile of leptin level (mean, 11.1 and 19.7 ng/mL for boys and girls,
      respectively) had higher body weight, BMI, WHR, BP, and insulin levels than
      children in the lowest quintile (mean, 1.1 and 3.9 ng/mL for boys and girls,
      respectively). Boys had a higher BMI, WHR, and BP levels, yet had lower leptin
      levels than girls. In both genders, BMI and plasma leptin levels were
      significantly positively correlated with BP. In multivariate regression analyses,
      plasma leptin levels were positively associated with BP; however, this
      association became insignificant among girls and even inversely associated with
      systolic BP among boys after adjusting for BMI. CONCLUSIONS: Obesity is
      positively associated with BP among school children in Taiwan; however, the role
      of plasma leptin on the development of obesity-related hypertension is still
      controversial among school children.

PMID- 11243305
TI  - Altered Mayer wave and baroreflex profiles in high spinal cord injury.
AB  - Spinal sympathetic neurons are distributed in cord segments from Th1 to L3. High
      spinal cord injury demonstrates severe orthostatic hypotension, but not lower
      cord injury. It remains to be clarified as to where is the critical spinal level
      disturbing neural cardiovascular regulations in response to orthostatic stress.
      To address this issue, beat-to-beat blood pressure (BP) (measured using a
      Finapres device) and RR interval (measured electrocardiographically) were
      recorded at rest and in a 60 degree head-up position in 26 patients with varying
      levels of spinal cord injury (C4 to Th12) and in 15 healthy (control) subjects.
      Sympathetic vascular tone was examined by the Mayer wave power spectrum of
      systolic blood pressure (SBP) variability. Baroreflex sensitivity was examined by
      transfer function analysis of SBP and RR interval variabilities. The Mayer wave
      power spectrum increased in response to postural shift in most patients injured
      at Th4 or below, whereas this parameter either remained unchanged or decreased in
      patients with higher-level injury. Baroreflex sensitivity tended to decrease with
      postural shift in patients injured at Th3 or below, whereas this parameter
      increased in all patients with higher-level injury. We divided spinal patients
      into high-level injury (Th3 or above, n = 14) and low-level injury (Th4 or below,
      n = 12) groups. Systolic blood pressure significantly fell (-10 +/- 4 mm Hg, P <
      .05) with postural shift in high-level injury group but did not change in low
      level injury group or in control subjects. The low-level injury group and the
      control group demonstrated essentially similar autonomic nervous responses to
      postural shift, ie, a significant increase in Mayer wave power and an
      insignificant decrease in baroreflex sensitivity. On the contrary, the high-level
      injury group showed opposite responses, ie, an insignificant decrease in Mayer
      wave power and a significant increase in baroreflex sensitivity in response to
      postural shift. We conclude that spinal cord injury at Th3 or above eliminates
      normal neural cardiovascular responses to mild orthostatic stress in humans.

PMID- 11243306
TI  - Autoantibodies to oxidized low-density lipoprotein in coronary artery disease.
AB  - BACKGROUND: The significance of antioxidized low-density lipoprotein (oxLDL)
      antibodies in atherogenesis is not yet clear, and there are conflicting data
      regarding anti-oxLDL levels in early hypertension. METHODS: The levels of anti
      oxLDL antibodies were studied in coronary artery disease patients with (n = 82)
      or without (n = 36) hypertension, in association to other risk factors for
      coronary artery disease. RESULTS: The levels of anti-oxLDL antibodies did not
      differ significantly between coronary artery disease patients with or without
      hypertension. (0.132 +/- 0.146 v 0.153 +/- 0.158 optical density at 405 nm,
      respectively; P = .48). No significant differences in anti-oxLDL antibodies were
      found between men and women with and without hypertension, between hypertensive
      patients with normal and abnormal blood pressure measurements, and between
      medicated and nonmedicated hypertensive patients. The presence of diabetes
      mellitus, smoking, and hypercholesterolemia, either solely or in combination, did
      not result in significant differences in antibody levels in the hypertensive or
      normotensive patients. CONCLUSIONS: Although the levels of oxLDL antibodies might
      be modified in early hypertension, once advanced coronary artery disease has
      developed the presence of hypertension does not affect anti-oxLDL levels.

PMID- 11243307
TI  - Effect of salt loading on nitric oxide synthase expression in normotensive rats.
AB  - Elevation of arterial blood pressure (BP) with high salt intake in Dahl salt
      sensitive rats is associated and perhaps, in part, due to downregulation of renal
      and vascular production of nitric oxide (NO) and nitric oxide synthase (NOS)
      expressions. Several recent studies have revealed a significant increase in BP in
      Sprague-Dawley rats on high salt intake. Given the apparent salt sensitivity of
      Sprague-Dawley rats, we hypothesized that chronic high salt intake may affect NO
      system in these rats in a manner resembling that reported in salt-sensitive (not
      salt-resistant) Dahl rats. The effects of a high salt diet (chow containing 8%
      NaCl) of 48-h or 3-week duration was studied on immunodetectable endothelial
      (eNOS), inducible (iNOS), and neuronal (nNOS) NOS expressions of relevant organs
      in male Sprague-Dawley rats. The results were compared with those obtained in the
      control animals fed a regular no-added salt diet (0.2% NaCl). Consumption of a
      high salt diet for 3 weeks induced hypertension (HTN) (158 +/- 6 v 115 +/- 5 mm
      Hg, P < .01) and widespread downregulation of iNOS expression in renal cortex,
      renal medulla, aorta, and heart. Similarly, chronic salt loading resulted in
      marked downregulation of eNOS expression in renal cortex and aorta and lowered
      expressions of nNOS in the brain, renal cortex, and renal medulla. In comparison,
      short-term salt loading resulted in significant reduction of iNOS in the renal
      cortex and aorta and of eNOS in the aorta together with significant elevation of
      nNOS expression in renal medulla and brain. Thus, chronic consumption of a high
      salt diet resulted in moderate HTN in normotensive Sprague-Dawley rats. This was
      accompanied by widespread downregulation of various NOS isotypes that undoubtedly
      contributed to the development and maintenance of HTN in this model.

PMID- 11243308
TI  - CoenzymeA glutathione disulfide is a potent modulator of angiotensin II-induced
      vasoconstriction.
AB  - CoenzymeA glutathione disulfide (CoASSG) has recently been isolated from bovine
      adrenal glands and is assumed to play an important role in blood pressure (BP)
      control. We used the isolated perfused rat kidney to investigate the modulating
      effects of CoASSG on angiotensin II (AngII)-induced vasoconstriction. Permanent
      perfusion with CoASSG (1 micromol/L) for 60 min induced a significant (P < .05)
      shift to the left in the dose-response curve for AngII (about 3.1-fold), whereas
      the dose-response curve for norepinephrine (NE) was unaffected. During continuous
      perfusion with 1 micromol/L CoASSG, the repetitive application of 10 pmol AngII
      significantly increased its vasoconstriction by 170% +/- 14% (P < .05) and 235%
      +/- 50% (P < .05) for 60 and 120 min, respectively. The potentiation of AngII by
      permanent perfusion with CoASSG is dose- and time-dependent and shows a plateau
      at 120 min. Glutathione, oxidized coenzymeA, and coenzymeA (each 1 micromol/L)
      are not able to enhance the vasoconstriction induced by AngII. We conclude that
      CoASSG is able to potentiate the vasoactive properties of AngII, and that CoASSG
      might play an important role in BP regulation via modulating effects of AngII.

PMID- 11243309
TI  - Lead-induced hypertension. III. Increased hydroxyl radical production.
AB  - Lead-induced hypertension has previously been shown to be closely associated with
      an increase in reactive oxygen species in low lead (100 ppm)-treated rats. The
      present study has attempted to define the specific moiety involved by noting the
      blood pressure (BP), reactive oxygen species (MDA-TBA), hydroxyl radical, and
      nitrotyrosine responses to infusion of the reactive oxygen species scavenger
      dimethylthiourea. Dimethylthiourea, a reputed scavenger of hydroxyl radical,
      normalized BP and MDA-TBA in the lead-treated rats but had no effect in normal
      control animals. MDA-TBA, hydroxyl radical, and nitrotyrosine, the tissue end
      product of peroxynitrite, were reduced to or toward normal by dimethylthiourea.
      The results, therefore, are consistent with the suggestion that either hydroxyl
      radical or peroxynitrite may be the reactive species affected by lead.

PMID- 11243310
TI  - Left ventricular hypertrophy and angiotensin II antagonists.
AB  - Left ventricular hypertrophy in patients with hypertension is an important
      condition. It is associated with significant mortality and carries increased risk
      for developing nonfatal cardiovascular complications, including coronary heart
      disease. The pathogenesis of left ventricular hypertrophy is linked to activation
      of the renin-angiotensin system, with excessive production of angiotensin II
      believed to be responsible. The therapeutic benefit of blocking angiotensin II at
      the receptor with selective angiotensin II antagonists, a relatively new class of
      antihypertensive agents, is therefore considered for regression of left
      ventricular hypertrophy. Clinical evidence shows significant efficacy in
      reversing left ventricular hypertrophy in hypertensive patients after treatment
      with angiotensin II antagonists. Published data include open-label and randomized
      studies with losartan treatment for left ventricular hypertrophy, with fewer
      studies investigating the effects of valsartan, irbesartan, and candesartan.

PMID- 11243311
TI  - The measurement of arterial properties in hypertension.

PMID- 11243312
TI  - Laragh's lessons in pathophysiology and clinical pearls for treating
      hypertension.

PMID- 11243313
TI  - Pulse pressure and aortic pulse wave are markers of cardiovascular risk in
      hypertensive populations.
AB  - BACKGROUND: Pulse pressure (PP) and aortic pulse wave velocity (PWV) are
      significant markers of cardiovascular risk, but a similar role for central wave
      reflections has never been investigated. PROCEDURES: To determine the factors
      influencing PP, PWV, and carotid wave reflections, a cohort of 1087 patients with
      essential hypertension either treated or untreated was studied cross-sectionally.
      Atherosclerotic alterations (AA) were defined on the basis of clinical events and
      PWV evaluated from an automatic device. The carotid amplification index (CAI), a
      quantitative estimation of the magnitude of central wave reflections, was
      measured noninvasively from pulse wave analysis using radial and carotid
      aplanation tonometry. RESULTS: In the overall population, age and mean arterial
      pressure represented 30.4%, 32.3%, and 5.6% of the variance of, respectively PP,
      PWV, and CAI. For the latter, body weight and heart rate represented 22.9% of
      variability. On the basis of logistic regression, AA were associated, in addition
      to age, plasma creatinine and HDL cholesterol levels, and tobacco consumption to
      three mechanical factors, increased PP, increased PWV, and low diastolic blood
      pressure, but not by CAI (adjusted odds ratio: 1.00; 95% confidence intervals:
      0.99-1.01). CONCLUSION: In cross-sectional hypertensive populations, PP and PWV,
      but not CAI, are significantly and independently associated with cardiovascular
      amplications.

PMID- 11243314
TI  - A systematic review of predictors of maintenance of normotension after withdrawal
      of antihypertensive drugs.
AB  - BACKGROUND: The identification and treatment of hypertension in the general
      community has contributed to the reduction in strokes and coronary heart disease
      observed during the past 30 years. However, concerns have arisen that some
      patients may be receiving unnecessary antihypertensive drug therapy leading to
      wasted resources and the potential for adverse drug effects. Once therapy has
      been started, treating physicians have difficulty in selecting patients for
      withdrawal and have concerns regarding patient safety and their own legal
      liability. PROCEDURES: This study reviews and consolidates information from
      published studies to identify known predictors of the successful maintenance of
      normotension after antihypertensive drug withdrawal. The predictors were
      identified by determining the proportion of subjects with various baseline
      characteristics who remained normotensive while off medication for at least 12
      months. From these data we have developed a clinical algorithm to help identify
      patients in whom antihypertensive drug withdrawal might be considered. This may
      assist primary care physicians in achieving successful withdrawal of
      antihypertensive therapy among selected hypertensive patients. RESULTS: The most
      consistent predictors identified were blood pressure (BP) (lower pretreatment, on
      treatment, and after withdrawal), nature of pharmacotherapy (fewer agents and
      lower dose), and preparedness to accept dietary intervention (weight and sodium
      reduction). CONCLUSIONS: On the basis of this information, a trial of withdrawal
      of antihypertensive medication might be recommended for patients who have mildly
      elevated, uncomplicated BP that is well controlled on a single agent, and who are
      motivated and likely to accept lifestyle changes.

PMID- 11243316
TI  - In vitro bioassay determination of dioxin-like and estrogenic activity in
      sediment and water from Ulsan Bay and its vicinity, Korea.
AB  - Extracts of sediment and water samples collected from Ulsan Bay, Korea, were
      screened for their ability to induce dioxin-like and estrogenic gene expression
      in vitro. Each sample was tested as raw extract (RE) and fractionated extract
      (FE). Based on the initial screening of RE, 23 of 31 sediment samples showed
      significant dioxin-like activity in H4IIE-luc bioassay, whereas most sediment
      samples did not elicit estrogenic response in MVLN bioassay. Most of the
      activities associated with FE samples revealed that mid-polar (F2) and most polar
      (F3) fractions were responsible for the significant reporter gene expression in
      H4IIE-luc bioassay. The results suggest that complex interactions may have
      depressed the activities of the known arylhydrocarbon receptor (AhR) agonists
      present in F1 samples. The F2 samples were the most active fraction. All F2
      samples except one induced significant dioxin-like activity, and over half of the
      F2 samples induced significant estrogenic activity. Ten of the F2 samples
      produced magnitudes of response in H4IIE-luc bioassay similar to those induced by
      a 2,3,7,8-tetrachlorodibenzo-p-dioxin standard. Sediment associated with F2
      samples was estimated to contain 24.9-826 pg TCDD-EQ/g DW. Based on a qualitative
      mass balance analysis, polycyclic aromatic hydrocarbons (PAHs) appeared to
      account for both the estrogenic and dioxin-like responses observed. Over half of
      the F3 samples were either cytotoxic or caused morphological changes in both
      H4IIE-luc and MVLN cells. Known concentrations of alkylphenols and bisphenol A
      were not great enough to account for both the estrogenic response and
      cytotoxicity observed for F3 samples. Despite the apparent toxic or stressful
      effects, most of F3 samples induced significant dioxin-like activity in vitro,
      adding to a growing body of evidence that suggests the presence of unidentified,
      relatively polar, AhR agonists in sediment from some areas.

PMID- 11243315
TI  - Trace organic contaminants in sediment and water from Ulsan Bay and its vicinity,
      Korea.
AB  - Sediment and water samples collected from 32 locations in Ulsan Bay and adjacent
      inland areas were analyzed for polycyclic aromatic hydrocabons (PAHs),
      nonylphenol (NP), octylphenol (OP), bisphenol A (BPA), organochlorine (OC)
      pesticides (HCB, HCHs, CHLs, and DDTs), and polychlorinated biphenyls (PCBs) to
      characterize their spatial distribution and contamination status. PAHs were
      detected in nearly all sediment and water extracts from Ulsan Bay and its inland
      locations. The sedimentary PAH concentrations ranged from 17 to 3,100 ng/g on a
      dry weight basis (DW), which were predominated by two- and three-ring aromatic
      hydrocarbons in river and/or stream, and four- to six-ring compounds in Ulsan Bay
      sediment. Concentrations of PAHs in pore water samples were generally two or
      three orders magnitude less than those of corresponding sediment samples. Maximum
      concentrations of NP, OP, and BPA in sediments were 1,040, 120, and 54 ng/g DW,
      respectively. Concentrations of OP and BPA were, on average, 5- to 13-fold less
      than those of NP. PCB concentrations in sediment ranged from 1.4 to 77 ng/g DW,
      which were predominated by lower chlorinated congeners such as di- through
      pentachlorinated biphenyls. Among different OC pesticides analyzed,
      concentrations of DDTs were the greatest, ranging from 0.02 to 41.9 ng/g DW. NP
      concentrations were greater at inner locations proximal to municipal wastewater
      discharges into rivers and/or streams, whereas the concentrations of PCBs and
      PAHs were great near the sites of high industrial activities. Sediment-pore water
      partitioning coefficients correlated with those of reported Koc or Kow values for
      selected PAHs in Ulsan Bay, but these varied by an order of magnitude for stream
      and/or river sediments.

PMID- 11243317
TI  - Distribution of inorganic mercury in Sacramento River water and suspended
      colloidal sediment material.
AB  - The concentration and distribution of inorganic Hg was measured using cold-vapor
      atomic fluorescence spectrometry in samples collected at selected sites on the
      Sacramento River from below Shasta Dam to Freeport, CA, at six separate times
      between 1996 and 1997. Dissolved (ultrafiltered, 0.005 microm equivalent pore
      size) Hg concentrations remained relatively constant throughout the system,
      ranging from the detection limit (< 0.4 ng/L) to 2.4 ng/L. Total Hg (dissolved
      plus colloidal suspended sediment) concentrations ranged from the detection limit
      at the site below Shasta Dam in September 1996 to 81 ng/L at the Colusa site in
      January 1997, demonstrating that colloidal sediment plays an important role in
      the downriver Hg transport. Sequential extractions of colloid concentrates
      indicate that the greatest amount of Hg associated with sediment was found in the
      "residual" (mineral) phase with a significant quantity also occurring in the
      "oxidizable" phase. Only a minor amount of Hg was observed in the "reducible"
      phase. Dissolved Hg loads remained constant or increased slightly in the
      downstream direction through the study area, whereas the total inorganic Hg load
      increased significantly downstream especially in the reach of the river between
      Bend Bridge and Colusa. Analysis of temporal variations showed that Hg loading
      was positively correlated to discharge.

PMID- 11243319
TI  - Long-term fate of glyphosate associated with repeated rodeo applications to
      control smooth cordgrass (Spartina alterniflora) in Willapa Bay, Washington.
AB  - Cordgrasses (Spartina sp.) are exotic, invasive species that threaten to degrade
      the intertidal zones of estuaries along the West Coast of North America.
      Integrated pest management (IPM) strategies primarily focus on the use of aerial
      and ground applications of Rodeo in conjunction with mowing, but IPM treatments
      over multiple years usually are necessary to control Spartina. Although
      information exists regarding the short-term fate and effects to marine biota of a
      single Rodeo application to control Spartina, little information is available
      regarding the fate and biotic effects associated with repeated Rodeo applications
      necessary for control. Consequently, we conducted a 3-year study to assess the
      short- and long-term fate and potential effects to marine biota associated with
      repeated applications of Rodeo to control smooth cordgrass in a southwestern
      Washington estuary. At each of three intertidal locations in Willapa Bay, we
      established plots on exposed mudflats and along the edge of a Spartina meadow
      that were hand sprayed with Rodeo (5% solution) and LI-700 (2% solution) during
      July 1997 and 1998. Glyphosate concentrations in sediment from mudflat plots
      declined 88% to 96% from 1 day posttreatment in 1997 to 1 year after the second
      Rodeo applications in 1999. In contrast, glyphosate concentrations in Spartina
      plots increased 231% to 591% from 1997 to 1999 because Spartina rhizomes likely
      did not readily metabolize or exude it. Comparison of concentrations from mudflat
      and Spartina plots with toxicity test values for marine biota indicates that
      under worst-case conditions short- and long-term detrimental effects to aquatic
      biota from repeated application of Rodeo for Spartina control would be highly
      unlikely.

PMID- 11243318
TI  - Polychlorinated biphenyls and organochlorine pesticides in soils from the
      southern part of Poland.
AB  - Surface soil and sediment samples collected from the cities of Krakow, Katowice,
      and Chorzow in 1993-94 were analyzed to determine the residual levels of
      persistent organochlorine pesticides (HCB, HCHs, DDTs, CHLs) and polychlorinated
      biphenyls (PCBs). Detection, identification, and quantification were made after a
      two-step clean-up and fractionation of sample extract with concentrated sulfuric
      acid and Florisil gel, followed by capillary gas chromatography with a 63Ni
      electron capture detector (GC-ECD) or a mass selective detector (GC-LRMS). The
      soil from the city of Katowice is relatively more polluted, mainly by PCBs but
      also by the other organochlorines. Both the soil in the cities of Krakow and
      Katowice are more polluted by organochlorines than soil from many other places in
      Poland. The residual concentrations of the organochlorines indicated nonexistence
      of the domestic sources of pollution by CHLs and elevated local contamination
      with PCBs. Sediment contained PCBs and CHLs in much higher concentrations than
      found in soil. In the case of DDTs, HCHs and HCB, the concentrations were of the
      same order of magnitude. Composition of DDT metabolites and of HCH isomers were
      investigated in detail.

PMID- 11243320
TI  - Effects of composting process and fly ash amendment on phytotoxicity of sewage
      sludge.
AB  - With the increasingly growing global production of sewage sludge, evaluation of
      its applicability in agriculture and land restoration is essential. This study
      assessed the potential effects of composting process and fly ash amendment on
      soil-ameliorating properties of sewage sludge. The metal availability and
      phytotoxicity of ash-amended sludge compost (AS, mature sewage sludge compost
      mixed with fresh lagoon ash) and sludge-ash co-compost (SA, co-composted mixture
      of sewage sludge and lagoon ash) were compared. The results of this work
      suggested that both composts favored the applicability of sewage sludge for land
      application by reducing Cd, Cu, Pb, and Zn availability. The SA co-compost
      stimulated seed germination at ash amendment rates of < or = 10%, whereas various
      treatments of AS compost inhibited germination at an extract dilution of 50%.
      Amendment of lagoon ash before or after sludge composting increased electrical
      conductivity (EC) and volatilization of NH4-N, but lowered availability of PO4-P.
      Together with the results of phytotoxicity, an optimal ash amendment rate of 5%
      for AS and 10% for SA were most desirable. Alkaline amendment prior to sludge
      composting was recommended, because it could be more effective in reducing
      soluble and plant-available metal concentrations through the composting process.

PMID- 11243321
TI  - Effects of copper sulfate on Typha latifolia seed germination and early seedling
      growth in aqueous and sediment exposures.
AB  - The vascular macrophyte Typha latifolia Linnaeus (common cattail) may be a
      sentinel for evaluating potential phytotoxicity to rooted aquatic macrophytes in
      aquatic systems. To further evaluate the potential utility of this species, T.
      latifolia seed germination, shoot growth, and root elongation were measured in 7
      day aqueous exposures using mean measured aqueous copper concentrations of 10.0,
      23, 41, 62, 174, and 402 microg Cu/L, which were > or = 62% of nominal
      concentrations. Seed germination and seedling shoot growth were not significantly
      affected by any of these copper concentrations as compared to controls. Mean
      measured no-observed-effect-concentration (NOEC) and lowest-observed-effect
      concentration (LOEC) for root elongation were 18.6 microg Cu/L and 35.0 microg
      Cu/L, respectively. Seven-day sediment tests were conducted by amending
      uncontaminated sediments with copper sulfate to mean measured concentrations of
      7.9, 17.1, 21.0, 51.2, 89.5, and 173.5 mg Cu/kg, which were > or = 84% of nominal
      concentrations. Seed germination was not significantly different from controls.
      Mean measured NOEC and LOEC values for seedling shoot growth were 89.5 mg Cu/kg
      and 173.5 mg Cu/kg, respectively, and mean measured NOEC and LOEC values for root
      growth were 14.0 mg Cu/kg and 19.7 mg Cu/kg, respectively. These results
      demonstrate that T. latifolia early seedling growth can be utilized for assessing
      aqueous and sediment toxicity of copper.

PMID- 11243322
TI  - Effects of atrazine and nicosulfuron on phytoplankton in systems of increasing
      complexity.
AB  - We have tested the sensitivity of phytoplankton to the herbicides atrazine and
      nicosulfuron in experiments conduced in increasingly complex systems, from single
      strain phytoplankton cultures (microplates) to mesocosms mimicking whole
      ecosystems. The endpoints used to assess sensitivity to atrazine and nicosulfuron
      were total biomass increase, photosynthetic efficiency, and community diversity,
      depending on the system considered. Nicosulfuron appeared to be very much less
      toxic to phytoplankton than atrazine, in accord with the planned changes in
      agricultural practices to reduce the effects of surface water contamination on
      aquatic biota. Nevertheless, nicosulfuron had significant effects in some systems
      (principally microcosms), whereas the single monocultures were almost insensitive
      to it. This points out the inaccuracy of standardized toxicity test on
      phytoplanktonic algae alone for predicting the effects of xenobiotics on natural
      communities and the need for tests in microcosms and mesocosms to obtain reliable
      evidence about the toxicity of a given chemical on freshwater aquatic ecosystems.

PMID- 11243323
TI  - Determination of cadmium partitioning in microalgae and oysters: contribution to
      the assessment of trophic transfer.
AB  - Alternative methodologies have been applied to the study of cadmium transfer in a
      food chain: water, microalgae (Skeletonema costatum and Tetraselmis suecica),
      oysters (Crassostrea gigas). The potential bioavailability of Cd in organisms was
      assessed through partitioning at the cell or tissue levels, and the predictive
      value of this method was evaluated by determining directly the metal transfer in
      an experimental food chain model. Cd concentrations were lower in S. costatum
      than T. suecica, in controls as well as in contaminated algae. In both algal
      species, Cd was firmly bound to the cell wall or had entered the cell. Cytosolic
      Cd was bound to intracellular ligands, the biochemical characteristics of which
      were not consistent with the hypothesis of detoxification via phytochelatins. In
      both algal species, Cd was predominantly present in the insoluble fraction, but
      at pHs such as those existing in the digestive tract of bivalves, it was easily
      extracted from the cells. Thus, exposure to Cd through phytoplanktonic food
      induced a significant uptake of this metal in soft tissues of bivalves. Due to
      the difference in Cd accumulation in algae, Cd doses associated with S. costatum
      were lower than those bound to T. suecica. Moreover, oysters retained a lower
      percentage of the metal associated with S. costatum compared to T. suecica (9 and
      20%, respectively, after 21 days of exposure). Cd doses potentially available to
      oysters exposed directly in sea water were considerably higher, and direct uptake
      induced the highest levels of Cd incorporation but only 2% of dissolved Cd was
      actually retained by oysters over 21 days of exposure. In the soft tissues of
      oysters, Cd was distributed equally between soluble and insoluble fractions.
      Cytosolic Cd was present predominantly in the heat-stable fraction and mainly
      bound to compounds of molecular weight equal to 13.5 kDa. Moreover, a positive
      correlation was observed between metallothionein-like protein (MTLP) levels and
      gross concentrations of Cd in the soft tissues of oysters. These data are
      consistent with the hypothesis of an important role of metallothioneins in Cd
      metabolism in oysters and suggest a potential availability of MT-bound fraction
      of Cd to the consumers. These data are in agreement with the response of oysters
      exposed to Cd in the field.

PMID- 11243324
TI  - Biochemical response of the mussel Mytilus galloprovincialis from Bizerta
      (Tunisia) to chemical pollutant exposure.
AB  - Three biomarkers (glutathione S-transferase [GST] activity, catalase [CAT]
      activity, and malonedialdehyde [MDA] levels) were measured in specimens of the
      mussel Mytilus galloprovincialis collected from two different stations (BC and
      MJ) in the lagoon of Bizerta (Tunisia). Animals were allowed to acclimate in the
      laboratory for some days. They were then exposed for 48 h to two concentrations
      of pp'DDE and two doses of mercury chloride. The acclimation period increased CAT
      activities and MDA levels in control mussels from both sites. GST activities were
      not modified during the acclimation period, whereas the sampling site of mussels
      appeared to exert a significant influence (higher values in control mussels from
      MJ than in those from BC). The treatment with both contaminants also increased
      GST activities of mussels from BC and not from MJ. It is hypothesized that
      animals from this last location are more exposed to the urban waste waster
      disposal, their biochemical response (GST activity) to pollutant exposure will be
      less marked. The treatment with pp'DDE or mercury did not show significant trend
      in CAT activities or MDA levels due to the variation of controls, and comparison
      of sites for mussels exposed to either pollutant therefore seems difficult. The
      acclimation period in the laboratory and the origin of mussels must be taken into
      consideration when studying the biochemical responses of mussels experimentally
      exposed to chemical pollutants.

PMID- 11243325
TI  - Interclonal variation in the acute and delayed toxicity of cadmium to the
      European prosobranch gastropod Potamopyrgus antipodarum (Gray).
AB  - The lethal responses of three European clones--A, B, and C-of the prosobranch
      snail Potamopyrgus antipodarum to acute cadmium exposure were examined by the use
      of a conventional LC50 test and a delayed toxicity test. The questions addressed
      were: (1) Are there differences in susceptibility (LC50 values and uniformity of
      response) among the three European clones of P. antipodarum? (2) Are the patterns
      of differences in susceptibility among clones observed in the LC50 test also
      observed for the delayed toxicity test? (3) Is there concordance in the ranking
      of susceptibility among clones under acute cadmium exposure and under chronic
      cadmium exposure? The results showed that the widths of the tolerance
      distribution differed among clones. Clones A and B had a steeper slope than clone
      C (for clone A the difference was marginally significant), which indicates that
      individuals from clones A and B showed a more uniform response to acute lethal
      cadmium stress than individuals from clone C. On the basis of the measured
      differences in LC50 values, clone A individuals showed the highest tolerance to
      acute cadmium (LC50 value: 1.92 mg Cd L(-1)) followed by clone B (LC50 value:
      1.29 mg Cd L(-1)) and clone C (LC50 value: 0.56 mg Cd L(-1)). Clone C was
      significantly less tolerant than clones A and B. The delayed toxicity test showed
      a similar pattern to the LC50 test with regard to tolerance differences among
      clones; however, mortality continued following transfer to clean water,
      indicating that cadmium was lethal at much lower concentrations than indicated by
      the conventional LC50 test. Results of the LC50 test and the delayed toxicity
      test in the present study were in general agreement with results from chronic
      cadmium exposure experiments (Jensen et al. [2000] Ecol Appl [submitted]), i.e.,
      the least susceptible clone A in the acute cadmium exposure test was also the
      least susceptible clone in the chronic cadmium exposure test. Based on the
      dramatic differences between the LC50 and the cadmium exposure concentrations
      causing delayed toxicity, we suggest that the potential for delayed toxicity
      should be given greater consideration in ecotoxicity testing.

PMID- 11243326
TI  - Element concentrations in the flesh and osteoderms of estuarine crocodiles
      (Crocodylus porosus) from the Alligator Rivers Region, Northern Australia: biotic
      and geographic effects.
AB  - The concentrations of Na, K, Ca, Mg, Ba, Sr, Fe, Al, Mn, Zn, Pb, Cu, Ni, Cr, Co,
      Se, U, and Ti were determined in the flesh and osteoderms of estuarine crocodiles
      (Crocodylus porosus) captured in three adjacent catchments of Kakadu National
      Park, within the Alligator Rivers Region of northern Australia. This study
      provides, for the first-time, baseline concentrations of elements in both flesh
      and osteoderms of wild crocodiles. Multiple linear regression analyses were used
      to determine the effects of total crocodile length, estimated age, gender,
      inferred reproductive status, physical condition, and catchment of capture on
      element concentrations in both tissues. The Mg concentration (log10) in the flesh
      and osteoderms of C. porosus significantly (p < or = 0.001) decreased with
      increasing length (1.7-5.0 m) and estimated age (5-40 years). Similarly, the Ti
      concentration (log10) in flesh significantly (p < or = 0.01) decreased with
      increasing length. In contrast, Zn and Se concentration (log10) in flesh
      significantly (p < or = 0.001) increased with increasing length and/or age,
      suggesting that these relationships are mediated by biological rather than
      environmental chemical factors. In flesh, Fe and Na concentrations (log10)
      significantly (p < or = 0.05) increased as the physical condition of C. porosus
      deteriorated. No significant (p > 0.05) effects of gender or inferred
      reproductive status on element concentrations in the flesh and osteoderms were
      found. The mean concentrations (log10) of Al, Ba, Cr, Ni, and Pb in flesh and Co,
      Fe, Mg, Mn, and U in the osteoderms were significantly (p < or = 0.01) different
      between catchments. The significant (p < or = 0.05) effects of catchment on the
      concentrations of various elements indicate that C. porosus reflects the
      chemistry of its environmental milieu and therefore has a certain degree of
      catchment fidelity, even though the catchments are adjacent to one another. Such
      catchment-specific signals may be useful in the determination of the provenance
      of itinerant crocodiles. They also point to the utility of crocodiles as long
      term biomonitors of their environment.

PMID- 11243327
TI  - Selenium, cadmium, copper, and zinc concentrations in sediments and mullet (Mugil
      cephalus) from the southern Basin of Lake Macquarie, NSW, Australia.
AB  - Selenium, cadmium, copper, and zinc concentrations were measured in sediments and
      the tissues of mullet (Mugil cephalus) collected from the southern basin of Lake
      Macquarie, NSW, Australia. Trace metals in surficial sediments are enriched in
      trace metals relative to background concentrations (selenium, 3-19; cadmium, 14
      42; copper, 1.5-3.6; zinc, 0.77-2.2 times background). Selenium, cadmium, and
      copper in Lake Macquarie mullet tissues are elevated compared to those in mullet
      collected from the Clyde River estuary, a relatively pristine location. Selenium
      and copper concentrations are also elevated compared to those reported in mullet
      tissues from other nonpolluted coastal environments. Zinc concentrations in Lake
      Macquarie mullet muscle tissues are significantly higher than those in muscle
      tissues of mullet from the Clyde River estuary, but mullet from both locations
      have similar zinc concentrations in other tissues. These results show that
      contamination of sediment with trace metals has resulted in elevated trace metals
      in the benthic feeding fish M. cephalus. Little of the variation of trace metal
      concentrations between fish was explained by variation in mass. Selenium
      concentrations in mullet are of concern in muscle tissues as they are above
      recommended acceptable limits for safe human consumption, while concentrations in
      tissues are at levels that may effect fish growth, reproduction, and survival.
      Copper concentrations in mullet tissues are also at levels that may reduce fish
      growth.

PMID- 11243328
TI  - Selenium and mercury concentrations in brood-stock walleye collected from three
      sites on Lake Oahe.
AB  - A decline in the walleye Stizostedion vitreum sport fishery in lower Lake Oahe,
      South Dakota, was documented in the early 1980s and has been attributed to poor
      natural reproduction and/or recruitment. Contaminants were suspected of causing
      low natural reproduction/recruitment in lower Lake Oahe as well as low
      hatchability of eggs produced from broodstock walleyes taken from lower Lake
      Oahe. Concentrations of dissolved selenium in the Cheyenne River, which enters
      lower Lake Oahe, have increased considerably over the last 15 years. To determine
      whether selenium concentrations contributed to the reproduction problems in the
      lower Lake Oahe walleye population, adult walleye were collected during spawning
      operations in April 1994, 1995, and 1996 to obtain tissue samples. Muscle, liver,
      reproductive tissue, and unfertilized eggs were analyzed with a modified
      fluorometric method for determining selenium concentrations in plants. These
      tissues were also analyzed for mercury content using cold-vapor atomic
      absorption. No statistical differences (p < 0.05) in selenium or mercury
      concentrations among sites could be determined that would explain differential
      walleye egg hatchability. Correlation analysis determined significant inverse
      associations existed between the gonadal somatic index of male walleye and
      gonadal tissue selenium concentrations (r = -0.41, p = 0.0012). Both walleye
      sexes exhibited significant inverse associations between the hepatic somatic
      index (HSI) and liver selenium concentrations (males r = -0.33, p = 0.0095; and
      females r = -0.38, p = 0.0034). Positive relationships existed for female walleye
      selenium concentrations in the liver and the ovaries (r = 0.37, p = 0.003) and
      the liver and muscle tissue (r = 0.28, p = 0.027). Mercury concentrations in
      walleye ovaries were positively correlated with HSI (r = 0.30, p = 0.0012),
      length (r = 0.36, p = 0.0046), relative weight (r = 0.36, p = 0.0054), and muscle
      concentrations (r = 0.49, p = 0.0001). Mercury concentrations in male walleye
      muscle were correlated with age (r = 0.57, p = 0.0001), length (r = 0.79, p =
      0.0001), and mercury concentrations in the testes (r = 0.43, p = 0.0006).

PMID- 11243329
TI  - The effect of different oil spill remediation techniques on petroleum hydrocarbon
      elimination in Australian bass (Macquaria novemaculeata).
AB  - Petroleum hydrocarbons were investigated in juvenile Australian bass, Macquaria
      novemaculeata, following exposure to the water accommodated fraction (WAF) of
      Bass Strait crude oil, chemically dispersed crude oil, and burnt crude oil. Each
      treatment was administered for 16 days either through the water column or through
      the diet (amphipod, Allorchestes compressa). Polycyclic aromatic hydrocarbon
      (PAH) elimination was determined by measuring biliary benzo(a)pyrene (B(a)P) and
      naphthalene-type metabolites. Biliary PAH-type metabolite concentrations varied
      with the type of oil spill remediation technique, route of exposure (food versus
      water), and exposure concentration. Fish exposed to chemically dispersed crude
      oil via the water exhibited the highest PAH-type biliary metabolite
      concentrations, relative to fish exposed to other treatments. In fish exposed via
      the diet, the highest concentration of both types of biliary metabolites also
      appeared in the dispersed oil-exposed individuals. The results suggest that
      chemically dispersing oil may have the greatest effect on bioavailability of
      hydrocarbons, both through waterborne and food chain exposures.

PMID- 11243330
TI  - Paper and pulp mill effluent-induced immunotoxicity in freshwater fish Channa
      punctatus (Bloch).
AB  - The influence of temperature variation on the humoral immune response using the
      plaque-forming cell (PFC) assay in freshwater fish Channa punctatus (Bloch) was
      investigated. The fish was exposed to 1% concentration (v/v in water) of paper
      and pulp mill effluent under standard laboratory conditions in glass aquaria.
      Effect of effluent exposure on the organ weight and organ cellularity was also
      evaluated. In general, lower temperature in winter produced a subdued response in
      control as well as experimental group. At higher temperature of summer and rainy
      seasons, an elevated response was observed. It was revealed that though
      suppressive effect of effluent was evident during all the seasons, in summer,
      extent of suppression was greater as compared to winter. Paper and pulp mill
      effluent exposure resulted in a decrease in the splenic and pronephric (head
      kidney) cellularity, with more pronounced effect in the summer season. We also
      studied the effects of the length of exposure on various parameters. Fish were
      exposed for 15, 30, 60, and 90 days to effluent. Short-term exposure for 15 days
      induced an elevated PFC response, but change was not statistically significant.
      Conversely, the exposure for 30, 60, and 90 days significantly reduced (p < 0.05
      0.001) the PFC response. Long-term exposure also caused significant reduction (p
      < 0.05-0.01) in the weights of lymphoid organs (spleen, head kidney, and total
      kidney). These results show a suppressive effect of chemical constituents of
      paper and pulp mill effluent on the immune functions. Furthermore, results
      demonstrated that though modulatory effect of the temperature on immune functions
      is recognized, it was not a major contributory factor to the elevated
      immunotoxicity of paper and pulp mill effluent in the seasons of high
      temperature.

PMID- 11243331
TI  - Changes in contaminant levels in New Jersey osprey eggs and prey, 1989 to 1998.
AB  - Ospreys are good indicators of the health of estuarine areas because they feed
      almost exclusively on fish with the balance on other aquatic biota. Through the
      1980s, ospreys nesting on Delaware Bay in New Jersey had reduced reproductive
      success relative to those nesting on the Atlantic coast and the Maurice River, a
      tributary of Delaware Bay. Earlier research suggested that elevated levels of DDT
      and polychlorinated biphenyl (PCB) contaminants identified in addled osprey eggs
      contributed to this reduced productivity. We repeated egg and prey sampling
      initially conducted in 1989 to evaluate the trends of contaminants in the last
      decade. Most organochlorine contaminants declined in osprey eggs in 1998 relative
      to 1989. Across three study areas, PCBs decreased from 4.1-7.7 ppm in 1989 to 1.8
      3.2 ppm in 1998; DDE decreased from 1.2-3.2 ppm in 1989 to 0.7-1.2 ppm in 1998.
      Lead in eggs increased from an average of 0.01 to 0.30 ppm wet weight, and
      mercury averaged 0.12 ppm and increased only in Atlantic coast eggs. Most of
      these contaminant changes were also found in typical prey fish: PCBs decreased
      from 0.18-1.2 ppm in 1989 to 0.06-0.43 ppm in 1998; DDE decreased from 0.05-0.69
      ppm in 1989 to 0.03-0.13 ppm in 1998. Lead and mercury increased in most fish
      samples. The improvement in most organochlorine contaminants in osprey eggs and
      prey reflected improved nest success in the Delaware Bay study area, and the
      nesting populations in the Atlantic and Maurice River study areas increased
      approximately 200% since 1989. PCBs and DDE in osprey eggs were below levels
      considered to be toxic to egg development. This study documents significant
      improvements in organochlorine contaminants in southern New Jersey ospreys, but
      justifies continued monitoring of heavy metals, such as lead and mercury, in
      aquatic ecosystems.

PMID- 11243332
TI  - Food chain aspects of chlordane poisoning in birds and bats.
AB  - We have observed recurring chlordane poisonings of large numbers of common
      grackles (Quiscalus quiscula), European starlings (Sturnus vulgaris), and
      American robins (Turdus migratorius) at suburban roosts in New Jersey during the
      month of July. This paper describes aspects of the food chain uptake of chlordane
      that account for the periodicity of these poisonings. Chlordane concentrations
      ranged from < 0.02 to 20.3 microg/g wet weight in 11 soil samples collected from
      residential lawns and a golf course near one roost. Of the 10 species of insects
      and soil invertebrates collected from the area, two scarab beetles, the oriental
      beetle (Anomala orientalis) and Japanese beetle (Popilla japonica), had the
      highest concentrations of chlordane-related compounds (15.1 and 5.9 microg/g wet
      weight, respectively). Concentrations in the other eight species ranged from <
      0.04 to 1.3 microg/g. Oriental and Japanese beetles collected from a rural
      location had concentrations of 0.03 and < 0.02 microg/g, respectively. Emergence
      of adult beetles peaked in mid- to late July, when bird mortality also peaked.
      Fecal pellets collected near the roost (n = 24) contained the remains of 1-5
      beetles each (mean = 2), and scarab beetles accounted for 40% of the total number
      of insect parts in the stomach contents of common grackles (n = 8). Unlike soil
      samples, in which cis- and trans-chlordane predominated, beetles contained large
      amounts of the more toxic metabolites heptachlor epoxide and oxychlordane. Total
      chlordane-related compounds ranged from < 0.05 to 18.4 microg/g in Japanese
      beetles collected from 16 sites in New Jersey and 2 sites in Ohio. The highest
      concentrations were found in beetles from suburban areas and golf courses. We
      also analyzed brain tissue from insectivorous bats (15 big brown bats, Eptesicus
      fuscus, and 5 little brown bats, Myotis lucifugus) that were submitted to the New
      Jersey Rabies Laboratory in late June/July 1998 and 1999 but found to be rabies
      negative. We suggest that high concentrations in three of the bats caused
      debility or abnormal behavior that may have precipitated submission for rabies
      testing.

PMID- 11243333
TI  - Monte Carlo techniques should replace analytical methods for estimating dose
      distributions in radiotherapy treatment planning.

PMID- 11243334
TI  - Conformal photon-beam therapy with transverse magnetic fields: a Monte Carlo
      study.
AB  - This work studies the idea of using strong transverse magnetic (B) fields with
      high-energy photon beams to enhance dose distributions for conformal
      radiotherapy. EGS4 Monte Carlo code is modified to incorporate charged particle
      transport in B fields and is used to calculate effects of B fields on dose
      distributions for a variety of high-energy photon beams. Two types of
      hypothetical B fields, curl-free linear fields and dipole fields, are used to
      demonstrate the idea. The major results from the calculation for the linear B
      fields are: (1) strong transverse B fields (> 1 T) with high longitudinal
      gradients (G) (> 0.5 T/cm) can produce dramatic dose enhancement as well as dose
      reduction in localized regions for high-energy photon beams; (2) the magnitude of
      the enhancement (reduction) and the geometric extension and the location of this
      enhancement (reduction) depend on the strength and gradient of the B field, and
      photon-beam energy; (3) for a given B field, the dose enhancement generally
      increases with photon-beam energy; (4) for a 5 T B field with infinite
      longitudinal gradient (solenoidal field), up to 200% of dose enhancement and 40%
      of dose reduction were obtained along the central axis of a 15 MV photon beam;
      and (5) a 60% of dose enhancement was observed over a 2 cm depth region for the
      15 MV beam when B = 5 T and G = 2.5 T/cm. These results are also observed,
      qualitatively, in the calculation with the dipole B fields. Calculations for a
      variety of B fields and beam configurations show that, by employing a well
      designed B field in photon-beam radiotherapy, it is possible to achieve a
      significant dose enhancement within the target, while obtaining a substantial
      dose reduction over critical structures.

PMID- 11243336
TI  - Measurements and Monte Carlo calculations to determine the absolute detector
      response of radiochromic film for brachytherapy dosimetry.
AB  - GafChromic (MD-55-2) radiochromic film has become increasingly popular for
      medical applications and has proven to be useful for brachytherapy dosimetry. To
      measure the absolute dose near a brachytherapy source, the response of the
      proposed detector in the measurement conditions relative to the response of the
      detector in calibration conditions must be known. MD-55-2 radiochromic film has
      been exposed in four different photon beams, a 30 and 40 kVp tungsten anode x-ray
      beam, a 75 kVp orthovoltage therapy beam, and a 60Co teletherapy beam to measure
      the relative detector response. These measurements were combined with coupled
      photon/electron Monte Carlo transport calculations to determine the absolute
      detector response. The Los Alamos National Laboratory Monte Carlo transport code
      MCNP4B2 was used. The measured relative response of this batch of MD-55-2 film
      varies from 8.79 mOD/Gy, measured for the 60Co beam, by as much as 42% for the
      low-energy x-ray beams. However, the absolute detector response varies from 4.32
      mOD/Gy for the 60Co beam by, at most, only 6.3%. In this work we demonstrate that
      the absolute detector response of MD-55-2 radiochromic film is a constant and
      independent of beam quality. Further, this work shows that MCNP4B2 accurately
      simulates the energy response and geometry artifacts of the radiochromic film.

PMID- 11243335
TI  - Monte Carlo dose calculations of beta-emitting sources for intravascular
      brachytherapy: a comparison between EGS4, EGSnrc, and MCNP.
AB  - The dose parameters for the beta-particle emitting 90Sr/90Y source for
      intravascular brachytherapy (IVBT) have been calculated by different
      investigators. At a distant distance from the source, noticeable differences are
      seen in these parameters calculated using different Monte Carlo codes. The
      purpose of this work is to quantify as well as to understand these differences.
      We have compared a series of calculations using an EGS4, an EGSnrc, and the MCNP
      Monte Carlo codes. Data calculated and compared include the depth dose curve for
      a broad parallel beam of electrons, and radial dose distributions for point
      electron sources (monoenergetic or polyenergetic) and for a real 90Sr/90Y source.
      For the 90Sr/90Y source, the doses at the reference position (2 mm radial
      distance) calculated by the three code agree within 2%. However, the differences
      between the dose calculated by the three codes can be over 20% in the radial
      distance range interested in IVBT. The difference increases with radial distance
      from source, and reaches 30% at the tail of dose curve. These differences may be
      partially attributed to the different multiple scattering theories and Monte
      Carlo models for electron transport adopted in these three codes. Doses
      calculated by the EGSnrc code are more accurate than those by the EGS4. The two
      calculations agree within 5% for radial distance <6 mm.

PMID- 11243337
TI  - On the validity of the superposition principle in dose calculations for
      intracavitary implants with shielded vaginal colpostats.
AB  - Intracavitary vaginal applicators typically incorporate internal shielding to
      reduce dose to the bladder and rectum. While dose distributions about a single
      colpostat have been extensively measured and calculated, these studies neglect
      dosimetric perturbations arising from the contralateral colpostat or the
      intrauterine tandem. Dosimetric effects of inhomogeneities in brachytherapy is
      essential for both dose-based implant optimization as well as for a comparison
      with alternate modalities, such as intensity modulated radiation therapy. We have
      used Monte Carlo calculations to model dose distributions about both a Fletcher
      Suit-Delclos (FSD) low dose-rate system and the microSelectron high dose-rate
      remote afterloading system. We have evaluated errors, relative to a Monte Carlo
      simulation based upon a complete applicator system, in superposition calculations
      based upon both precalculated single shielded applicator dose distributions as
      well as single unshielded source dose distributions. Errors were largely
      dominated by the primary photon attenuation, and were largest behind the shields
      and tandem. For the FSD applicators, applicator superposition showed differences
      ranging from a mean of 2.6% at high doses (>Manchester Point A dose) to 4.3% at
      low doses (<Manchester Point A dose) compared to the full geometry simulation.
      Source-only superposition yielded errors higher than 10% throughout the dose
      range. For the HDR applicator system, applicator superposition-induced errors
      ranging from 3.6%-6.3% at high and low doses, respectively. Source superposition
      caused errors of 5%-11%. These results indicate that precalculated applicator
      based dose distributions can provide an excellent approximation of a full
      geometry Monte Carlo dose calculation for gynecological implants.

PMID- 11243338
TI  - Dosimetry of 192Ir wires for LDR interstitial brachytherapy following the AAPM TG
      43 dosimetric formalism.
AB  - Implementation of the AAPM Task Group 43 dosimetric formalism for 192Ir wires
      used as interstitial sources in low dose-rate (LDR) brachytherapy applications is
      investigated. Geometry factors, dose-rate constant values, radial dose functions,
      and anisotropy functions, utilized in this formalism, were calculated for various
      lengths of all commercially available wire source designs by means of a well
      established Monte Carlo simulation code and an improved modification of the
      Sievert integral method. Results are presented in the form of look up tables that
      allow interpolation for dose-rate calculations around all practically used wire
      lengths, with accuracy acceptable for clinical applications.

PMID- 11243339
TI  - Real-time monitoring and verification of in vivo high dose rate brachytherapy
      using a pinhole camera.
AB  - We investigated a pinhole imaging system for independent in vivo monitoring and
      verification of high dose rate (HDR) brachytherapy treatment. The system consists
      of a high-resolution pinhole collimator, an x-ray fluoroscope, and a standard
      radiographic screen-film combination. Autofluoroscopy provides real-time images
      of the in vivo Ir-192 HDR source for monitoring the source location and movement,
      whereas autoradiography generates a permanent record of source positions on film.
      Dual-pinhole autoradiographs render stereo-shifted source images that can be used
      to reconstruct the source dwell positions in three dimensions. The dynamic range
      and spatial resolution of the system were studied with a polystyrene phantom
      using a range of source strengths and dwell times. For the range of source
      activity used in HDR brachytherapy, a 0.5 mm diameter pinhole produced sharp
      fluoroscopic images of the source within the dynamic range of the fluoroscope.
      With a source-to-film distance of 35 cm and a 400 speed screen-film combination,
      the same pinhole yielded well recognizable images of a 281.2 GBq (7.60 Ci) Ir-192
      source for dwell times in the typical clinical range of 2 to 400 s. This 0.5 mm
      diameter pinhole could clearly resolve source positions separated by lateral
      displacements as small as 1 mm. Using a simple reconstruction algorithm, dwell
      positions in a phantom were derived from stereo-shifted dual-pinhole images and
      compared to the known positions. The agreement was better than 1 mm. A
      preliminary study of a patient undergoing HDR treatment for cervical cancer
      suggests that the imaging method is clinically feasible. Based on these studies
      we believe that the pinhole imaging method is capable of providing independent
      and reliable real-time monitoring and verification for HDR brachytherapy.

PMID- 11243340
TI  - Dependence of virtual wedge factor on dose calibration and monitor units.
AB  - One of the important features of the Siemens Virtual Wedge (VW) is that the VW
      factor (VWF) is approximately equal to unity for all beams with a total deviation
      for a given wedge no greater than 0.05, as specified by Siemens. In this note we
      report the observed dependence of VWF on dose calibration (cGy/MU), monitor units
      (MU), and beam tuning for a Primus, a linear accelerator with two dose-rate
      ranges available for VW operation. The VWF is defined as the ratio of doses
      measured on the beam central axis for the wedge field to the open field; the open
      field dose is always measured with the nominal high dose-rate beam. When VW
      operates in the high dose-rate range, the VWF is independent of calibration
      (cGy/MU). When VW works in the low dose-rate range, the VWF varies linearly with
      the calibration of the low dose-rate mode. For a linear accelerator that has only
      one dose-rate range for VW, there is no observable dependence of VWF on the
      calibration. We also studied the monitor unit dependence of VWF. A discontinuity
      in VWF was observed at the switching point between the high and low dose-rate
      ranges. Working with Siemens, we have investigated causes of this discontinuity.
      As a result of this investigation, the discontinuity in VWF as a function monitor
      unit is practically removed.

PMID- 11243341
TI  - Optimal detection of the neutron capture therapy agent borocaptate sodium (BSH):
      a comparison between 1H and 10B NMR.
AB  - Boron Neutron Capture Therapy (BNCT), an experimental binary cancer treatment
      modality, requires selective targeting of 10B containing compounds to tumors. One
      of the compounds under evaluation in an EORTC phase I trial, and used in Japan
      for patient treatments for many years, is borocaptate sodium (BSH, also known as
      sulfhydril boron hydride). To optimize the clinical applications, a noninvasive
      method is needed to monitor the distribution of the boron compound, and NMR may
      offer such a possibility. A comparison between the relative sensitivities for
      detecting BSH by 10B or 1H NMR was conducted at two magnetic field strengths: 2
      and 4.7 T. At each field strength, similar-sized radio frequency (rf) coils were
      used for both nuclei. Theoretical predictions for the intrinsic signal to noise
      (S/N) advantage of 1H over 10B detection vary between a factor of 5.4 and a
      factor of 28.9, depending on whether the effective resistance is dominated by
      coil losses or sample losses. Our tests, conducted on relatively small aqueous
      samples, which loaded the coils less than expected for animal or human subjects,
      resulted nevertheless in advantage factors close to the lower limit of this
      range. The measured S/N detection advantage factors for 1H were about 5.2 at 4.7
      T, using a dedicated 1H coil, and 7.7 at 2 T, where the measurements were
      conducted with a double-tuned coil. However, when predicting the expected
      performance for in vivo MRS or MRI, one should bear in mind that proton detection
      has to be conducted by spectral-editing pulse sequences with an inherent S/N loss
      by at least a factor of 2, and that the T1 relaxation time for 10B in BSH is
      about 30 times shorter than the 1HT1 value. In view of these considerations,
      direct 10B detection could well be the preferred strategy for MRI/MRS of BSH in
      vivo.

PMID- 11243342
TI  - A comparison of neutron beams for BNCT based on in-phantom neutron field
      assessment parameters.
AB  - In this paper our in-phantom neutron field assessment parameters, T and DTumor,
      were used to evaluate several neutron sources for use in BNCT. Specifically,
      neutron fields from The Ohio State University (OSU) Accelerator-Based Neutron
      Source (ABNS) design, two alternative ABNS designs from the literature (the
      Al/AIF3-Al2O3 ABNS and the 7LiF-AI2O3 ABNS), a fission-convertor plate concept
      based on the 500-kW OSU Research Reactor (OSURR), and the Brookhaven Medical
      Research Reactor (BMRR) facility were evaluated. In order to facilitate a
      comparison of the various neutron fields, values of T and DTumor were calculated
      in a 14 cm x 14 cm x 14 cm lucite cube phantom located in the treatment port of
      each neutron source. All of the other relevant factors, such as phantom
      materials, kerma factors, and treatment parameters, were kept the same. The
      treatment times for the OSURR, the 7LiF-Al2O3 ABNS operating at a beam current of
      10 mA, and the BMRR were calculated to be comparable and acceptable, with a
      treatment time per fraction of approximately 25 min for a four fraction treatment
      scheme. The treatment time per fraction for the OSU ABNS and the Al/AlF3-Al2O3
      ABNS can be reduced to below 30 min per fraction for four fractions, if the
      proton beam current is made greater than approximately 20 mA. DTumor was
      calculated along the bean centerline for tumor depths in the phantom ranging from
      0 to 14 cm. For tumor depths ranging from 0 to approximately 1.5 cm, the value of
      DTumor for the OSURR is largest, while for tumor depths ranging from 1.5 to
      approximately 14 cm, the value of DTumor for the OSU-ABNS is the largest.

PMID- 11243343
TI  - Lung dose calculations at kilovoltage x-ray energies using a model-based
      treatment planning system.
AB  - The determination of the dose to organs from diagnostic x rays has become
      important because of reports of radiation injury to patients from
      fluoroscopically guided interventional procedures. We have modified a
      convolution/superposition-based treatment planning system to compute the dose
      distribution for kilovoltage beams. We computed lung doses using this system and
      compared them to those calculated using the CDI3 organ dose calculation program.
      We also computed average lung doses from a simulated radiofrequency ablation
      procedure and compared our results to published doses for a similar procedure.
      Doses calculated using this system were an average of 20% lower for AP beams and
      7% higher for PA beams than those obtained using CDI3. The ratio of the average
      dose to the lungs to the skin dose from the simulated ablation procedure ranged
      from 25% higher to 15% lower than that determined by other authors. Our results
      show that a treatment planning system designed for use in the megavoltage energy
      range can be used for calculating organ doses in the diagnostic energy range. Our
      doses compare well with those previously reported. Differences are partly due to
      variations in experimental techniques. Using a three-dimensional (3-D) treatment
      planning system to calculate dose also allows us to generate dose volume
      histograms (DVH) and compute normal tissue complication probabilities (NTCP) for
      diagnostic procedures.

PMID- 11243344
TI  - On the use of pediatric phantoms in the dose evaluation during computed
      tomography (CT) thorax examinations.
AB  - This paper presents the dosimetric results obtained during computed tomography
      (CT) thorax examinations, carried out using two different techniques, i.e.,
      sequential CT (SQCT) and helical CT (HECT). The radiological examinations have
      been carried out on pediatric phantoms expressly designed and realized. Four
      different phantoms have been realized, according to the children shapes of 0, 2,
      6, and 12 years old. The dosimetric measurements have been carried out using
      thermoluminescent dosimeters. The comparison of the dosimetric data obtained
      using the two different techniques shows that there is not any relevant
      difference between them as far as the entrance dose and the doses received by the
      critical organs are concerned.

PMID- 11243345
TI  - Measurement of the dose deposition characteristics of x-ray fluoroscopy beams in
      water.
AB  - The purpose of this study was to characterize the x-ray dose distribution of
      fluoroscopy beams by measuring their percent depth dose curves and lateral dose
      profiles in a water phantom. Percent depth dose curves were measured near the
      surface with an Attix parallel plate chamber and deep within the water phantom
      with a Farmer-type cylindrical chamber. Percent depth dose curves were compared
      to published data where applicable. Lateral dose profiles were measured at depths
      of 2, 5, 10, and 15 cm in phantom with a Farmer chamber. Pulsed, 50 mA x-ray
      beams with peak tube potentials of 60, 80, 100, and 120 kV and half value layers
      of 1.89, 2.52, 3.20, and 4.09 mm Al, respectively, were investigated.

PMID- 11243346
TI  - X-ray forward-scatter imaging: experimental validation of model.
AB  - In our research program we have investigated, through modeling and related
      numerical calculations, the potential use of scattered photons for medical x-ray
      imaging. In this work, we present an experimental validation of the primary and
      of the forward-scatter x-ray imaging models. Incident polyenergetic photon beams
      generated from a conventional rotating anode x-ray tube were used. To compare
      quantitatively the results between primary and forward-scatter imaging, an
      ionization chamber was used to record the incident air collision kerma, Kair(c).
      Plots of contrast (C) and the signal-to-noise ratio (SNR) as a function of the
      imaging task are presented. We have chosen to make measurements with plastics
      [polymethyl methacrylate (PMMA), polycarbonate, polystyrene, polyethylene, and
      nylon] placed at the center of a 15 cm diam spherical water phantom. Good
      agreement between experiment (expt) and prediction (pred) was obtained for many
      imaging tasks. For example, to image a 2 cm thick PMMA/polycarbonate combination
      using an 80 kV beam with the primary photons we obtain Cexpt = 0.01 +/- 0.02,
      Cpred = 0.008 +/- 0.002, SNRexp/square root Kair(c) = 0.86 +/- 1.6(mJ/kg)(-1/2)
      and SNRpred/square root K(air)c = 0.51 +/- 0.14(mJ/kg)(-1/2). The values obtained
      by using the theta = 4 degrees scattered field were Cexpt = 0.26 +/- 0.06, Cpred
      = 0.19 +/- 0.01, SNRexp/square root Kair(c) = 3.8 +/- 0.8(mJ/ kg)(-1/2), and
      SNRpred/square root K(air(c) = 3.2 +/- 0.3 (mJ/kg)(-1/2) We have, however, shown
      that using form factor data from different authors can have a significant effect
      on the predicted values of C and SNR. The use of our semianalytic expressions for
      the numbers of transmitted and scattered photons combined with our experimental
      measurements allowed us to quantify the amount of water contamination in our
      measurements. Some preliminary results in air with biological materials (liver,
      muscle, water) are also presented. We are confident that our model can be used as
      a tool for designing and optimizing an x-ray scatter imaging system.

PMID- 11243347
TI  - Cone-beam computed tomography with a flat-panel imager: magnitude and effects of
      x-ray scatter.
AB  - A system for cone-beam computed tomography (CBCT) based on a flat-panel imager
      (FPI) is used to examine the magnitude and effects of x-ray scatter in FPI-CBCT
      volume reconstructions. The system is being developed for application in image
      guided therapies and has previously demonstrated spatial resolution and soft
      tissue visibility comparable or superior to a conventional CT scanner under
      conditions of low x-ray scatter. For larger objects consistent with imaging of
      human anatomy (e.g., the pelvis) and for increased cone angle (i.e., larger
      volumetric reconstructions), however, the effects of x-ray scatter become
      significant. The magnitude of x-ray scatter with which the FPI-CBCT system must
      contend is quantified in terms of the scatter-to-primary energy fluence ratio
      (SPR) and scatter intensity profiles in the detector plane, each measured as a
      function of object size and cone angle. For large objects and cone angles (e.g.,
      a pelvis imaged with a cone angle of 6 degrees), SPR in excess of 100% is
      observed. Associated with such levels of x-ray scatter are cup and streak
      artifacts as well as reduced accuracy in reconstruction values, quantified herein
      across a range of SPR consistent with the clinical setting. The effect of x-ray
      scatter on the contrast, noise, and contrast-to-noise ratio (CNR) in FPI-CBCT
      reconstructions was measured as a function of SPR and compared to predictions of
      a simple analytical model. The results quantify the degree to which elevated SPR
      degrades the CNR. For example, FPI-CBCT images of a breast-equivalent insert in
      water were degraded in CNR by nearly a factor of 2 for SPR ranging from
      approximately 2% to 120%. The analytical model for CNR provides a quantitative
      understanding of the relationship between CNR, dose, and spatial resolution and
      allows knowledgeable selection of the acquisition and reconstruction parameters
      that, for a given SPR, are required to restore the CNR to values achieved under
      conditions of low x-ray scatter. For example, for SPR = 100%, the CNR in FPI-CBCT
      images can be fully restored by: (1) increasing the dose by a factor of 4 (at
      full spatial resolution); (2) increasing dose and slice thickness by a factor of
      2; or (3) increasing slice thickness by a factor of 4 (with no increase in dose).
      Other reconstruction parameters, such as transaxial resolution length and
      reconstruction filter, can be similarly adjusted to achieve CNR equal to that
      obtained in the scatter-free case.

PMID- 11243348
TI  - Comparison of vessel contrast measured with a scanning-beam digital x-ray system
      and an image intensifier/television system.
AB  - Vessel contrast was measured in the fluoroscopic images produced by a scanning
      beam digital x-ray (SBDX) system and an image intensifier/television (II/TV)
      based system. The SBDX system electronically scans a series of pencil x-ray beams
      across the patient, each of which is directed at a distant small-area detector
      array. The reduction in detected scatter achieved with this geometry was expected
      to provide an increase in image contrast. Vessel contrast was evaluated from
      images of a phantom containing iodinated tubes. The vessels were inserted into an
      acrylic stack to provide a patient-mimicking scattering medium. Vessel diameter
      ranged from 0.3 to 3.1 mm. Images were acquired at 100 kVp with the SBDX and
      II/TV systems and averaged to reduce x-ray noise. The II/TV system was operated
      in the 6-in. image intensifier mode with an anti-scatter grid. The increase in
      contrast in the SBDX images, expressed as a ratio of the measured SBDX and II/TV
      contrasts, ranged from 1.63 to 1.79 for individual vessels. This agreed well with
      a prediction of the contrast improvement ratio for this experiment, based on
      measurements of the scatter fraction, object-plane line spread functions, and
      consideration of the source spectrum and detector absorption properties. The
      predicted contrast improvement ratio for SBDX relative to II/TV images was 1.62
      to 1.77.

PMID- 11243349
TI  - Effects of x-ray spectra on the DQE of a computed radiography system.
AB  - The effect of incident x-ray beam quality on the measured detective quantum
      efficiency (DQE) of a computed radiography system was investigated. The incident
      x-ray beams used had peak tube potentials of 70, 95, and 120 kVp, were filtered
      with various thicknesses of a "patient equivalent phantom" (PEP), aluminum, and
      copper, and provided a consistent exposure to the storage phosphor. For each peak
      tube potential and filter combination, the one-dimensional modulation transfer
      function and noise power spectrum were measured and the square of the incident
      signal-to-noise ratio was estimated. The spatial frequency dependent DQE was
      calculated from these data. The DQE was integrated to provide an overall estimate
      of the efficiency and frequency response of the computed radiography system for
      the various x-ray beams. There was found to be a wide range of integral DQE
      (IDQE) values for the peak tube potential and filter combinations used. For
      example, the IDQE ranged from 3.0 to 0.9 mm(-2) using the peak tube potential and
      filter combinations 70 kVp with 5.1 cm PEP and 120 kVp with 30.3 cm PEP,
      respectively. Finally, peak tube potential and filter combinations 70 kVp with
      10.2 cm PEP and 120 kVp with 20.2 cm PEP were chosen as standard x-ray beams that
      will be used at our facility to measure the DQE of digital radiographic imaging
      systems for evaluation and acceptance testing.

PMID- 11243350
TI  - False-positive reduction in CAD mass detection using a competitive classification
      strategy.
AB  - High false-positive (FP) rate remains to be one of the major problems to be
      solved in CAD study because too many false-positively cued signals will
      potentially degrade the performance of detecting true-positive regions and
      increase the call-back rate in CAD environment. In this paper, we proposed a
      novel classification method for FP reduction, where the conventional "hard"
      decision classifier is cascaded with a "soft" decision classification with the
      objective to reduce false-positives in the cases with multiple FPs retained after
      the "hard" decision classification. The "soft" classification takes a competitive
      classification strategy in which only the "best" ones are selected from the pre
      classified suspicious regions as the true mass in each case. A neural network
      structure is designed to implement the proposed competitive classification.
      Comparative studies of FP reduction on a database of 79 images by a "hard"
      decision classification and a combined "hard"-"soft" classification method
      demonstrated the efficiency of the proposed classification strategy. For example,
      for the high FP sub-database which has only 31.7% of total images but accounts
      for 63.5% of whole FPs generated in single "hard" classification, the FPs can be
      reduced for 56% (from 8.36 to 3.72 per image) by using the proposed method at the
      cost of 1% TP loss (from 69% to 68%) in whole database, while it can only be
      reduced for 27% (from 8.36 to 6.08 per image) by simply increasing the threshold
      of "hard" classifier with a cost of TP loss as high as 14% (from 69% to 55%). On
      the average in whole database, the FP reduction by hybrid "hard"-"soft"
      classification is 1.58 per image as compared to 1.11 by "hard" classification at
      the TP costs described above. Because the cases with high dense tissue are of
      higher risk of cancer incidence and false-negative detection in mammogram
      screening, and usually generate more FPs in CAD detection, the method proposed in
      this paper will be very helpful in improving the performance of early detection
      of breast cancer with CAD.

PMID- 11243351
TI  - Segmentation of suspicious densities in digital mammograms.
AB  - State-of-the-art algorithms for detection of masses in mammograms are very
      sensitive but they also detect many normal regions with slightly suspicious
      features. Based on segmentations of detected regions, shape and intensity
      features can be computed that discriminate between normal and abnormal regions.
      These features can be used to discard false positive detections and hence improve
      the specificity of the detection method. In this work two different methods to
      segment suspect regions were examined. A number of different implementations of a
      region growing method were compared to a discrete dynamic contour method. Both
      methods were applied to a consecutive data set of 132 mammograms containing
      masses and architectural distortions, taken from the Dutch screening program.
      Evaluation of the performance of the methods was done in two different ways. In
      the first experiment, the segmentations of masses were compared to annotations
      made by the radiologist. In the second experiment, a number of features were
      computed for all segmented areas, normal and abnormal, based on which regions
      were classified with a neural network. The most sophisticated region growing
      method and the method using the dynamic contour model had a similar performance
      when evaluation was based on the overlap of the annotations. The second
      experiment showed that the contours generated by the discrete dynamic contour
      model were more suited for computation of discriminating features. Contrast
      features were especially useful to improve the performance of the detection
      method.

PMID- 11243352
TI  - Automated measurement of radiographic hip joint-space width.
AB  - Radiographic joint-space narrowing (JSN) is the principle indicator of cartilage
      loss in osteoarthritis (OA). JSN is usually assessed qualitatively by visual
      inspection or in clinical research, is measured manually with a graduated
      handheld lens directly applied to the x-ray film, or from digitized radiographs
      by hand tracing the joint margins with a mouse. The minimum joint-space width
      (mJSW) and joint-space area (JSA) are recorded as the indices of OA progression
      in epidemiological studies and clinical drug trials. We present a computerized
      method that automatically finds the articular margins of the hip to improve
      determination of mJSW and JSA. The algorithm requires that three seed points are
      manually identified on the femoral head and uses three steps to process each
      digitized hip x-ray. First, a Hough transform finds the center and radius (R) of
      a circle that approximates the femoral head. Finding R indicates whether
      magnification differences must be corrected on repeat exams. Second, a gradient
      algorithm finds the edge of the femoral head and acetabulum. Third, the mid-line
      of the femoral neck is automatically found and used to define the joint portion
      (theta) that is assessed for narrowing. theta is fixed for follow-up exams of the
      same subject. The algorithm was evaluated in three ways to determine its
      performance characteristics. First, the inter-reader and intra-reader variability
      for mJSW and JSA associated with the selection of the seed points was found to be
      negligible (< 1%) compared to the variability associated with manual scoring with
      a lens or by tracing the joint margins with a mouse. Second, from duplicate hip x
      rays of 19 subjects with OA, the Root Mean Square Standard Deviation and
      coefficient of variation for mJSW and JSA defined by the algorithm was determined
      to be better than manual techniques by at least a factor of 2. Third, the
      algorithm correctly identified the joint margin in more than 85% of the 105 cases
      tested. Automated measures of radiographic hip joint-space narrowing is less
      subjective than manual methods and may be applicable for monitoring OA
      progression in clinical research.

PMID- 11243353
TI  - Evaluation of scatter compensation methods by their effects on parameter
      estimation from SPECT projections.
AB  - Three algorithms for scatter compensation in Tc-99m brain single-photon emission
      computed tomography (SPECT) were optimized and compared on the basis of the
      accuracy and precision with which lesion and background activity could be
      simultaneously estimated. These performance metrics are directly related to the
      clinically important tasks of activity quantitation and lesion detection, in
      contrast to measures based solely on the fidelity of image pixel values. The
      scatter compensation algorithms were (a) the Compton-window (CW) method with a
      20% photopeak window, a 92-126 keV scatter window, and an optimized "k-factor,"
      (b) the triple-energy window (TEW) method, with optimized widths of the photopeak
      window and the abutting scatter window, and (c) a general spectral (GS) method
      using seventeen 4 keV windows with optimized energy weights. Each method was
      optimized by minimizing the sum of the mean-squared errors (MSE) of the estimates
      of lesion and background activity concentrations. The accuracy and precision of
      activity estimates were then determined for lesions of different size, location,
      and contrast, as well as for a more complex Bayesian estimation task in which
      lesion size was also estimated. For the TEW and GS methods, parameters optimized
      for the estimation task differed significantly from those optimized for global
      normalized pixel MSE. For optimal estimation, the CW bias of activity estimates
      was larger and varied more (-2% to 22%) with lesion location and size than that
      of the other methods. The magnitude of the TEW bias was less than 7% across most
      conditions, although its precision was worse than that of CW estimates. The GS
      method performed best, with bias generally less than 4% and the lowest variance;
      its root-mean square (rms) estimation error was within a few percent of that
      achievable from primary photons alone. For brain SPECT, estimation performance
      with an optimized, energy-based, subtractive correction may approach that of an
      ideal scatter-rejection procedure.

PMID- 11243354
TI  - E. P. Pope Memorial Award to Dr. Alex A. Ardans.

PMID- 11243355
TI  - Immunohistochemical detection of avian pneumovirus in formalin-fixed tissues.
AB  - An immunohistochemical staining technique (IHC) was developed to detect avian
      pneumovirus (APV) antigen in formalin-fixed, paraffin-embedded tissue sections
      using streptavidin-biotin immunoperoxidase staining. Samples of nasal turbinates
      and infraorbital sinuses were collected from 4-week-old poults experimentally
      inoculated with APV and from older turkeys infected during naturally occurring
      outbreaks of avian pneumovirus. Tissue was fixed in 10% buffered neutral
      formalin, embedded in paraffin, sectioned and stained. Inflammatory changes were
      observed microscopically in the mucosa and submucosa of the nasal turbinates and
      infraorbital sinuses of both experimentally inoculated poults and naturally
      infected birds. Viral antigen was detected by IHC in the ciliated epithelial
      cells of nasal turbinates and infraorbital sinuses.

PMID- 11243356
TI  - An indirect enzyme-linked immunosorbent assay for diagnosis of American canine
      hepatozoonosis.
AB  - American canine hepatozoonosis (ACH), caused by Hepatozoon americanum, is an
      emerging tick-borne disease of dogs. An indirect enzyme-linked immunosorbent
      assay (ELISA) that should facilitate diagnosis of infection and study of the
      epidemiology of ACH has been developed using H. americanum sporozoites as
      antigen. Efficacy of the new test as a diagnostic tool was compared with that of
      skeletal muscle biopsy, the current gold standard for confirming H. americanum
      infection. Results show that the test is sensitive (93%) and specific (96%) and
      that it is as reliable as histopathologic examination of skeletal muscle for
      detecting infection. The ELISA would be suitable as a routine laboratory test for
      diagnosis of ACH.

PMID- 11243357
TI  - Polyclonal sandwich ELISAs to detect F18 fimbriated Escherichia coli in pigs in
      Northern Ireland.
AB  - F18 fimbriated Escherichia coli are a newly described cause of postweaning
      diarrhea in pigs. Polyclonal rabbit antisera were raised to the antigenic
      variants, F18ab and F18ac, of these fimbriae and were used to develop
      monospecific sandwich enzyme-linked immunosorbent assays (ELISAs). The ELISAs
      were standardized with type cultures characterized by polymerase chain reaction
      techniques (PCR) and then used to conduct a study of the prevalence of F18
      fimbriated E. coli in pigs in Northern Ireland. A total of 176 isolates were
      tested by ELISA and PCR. Eight isolates were positive for F18 by ELISA, of which
      2 were shown to be false positives by PCR and one was PCR positive but ELISA
      negative. Of the 6 confirmed ELISA positives, all produced VT2 toxin and 3
      produced ST toxin. Four positives were from serogroups O138 and O139, previously
      associated with porcine diarrhea.

PMID- 11243358
TI  - Prevalence of the enteroaggregative Escherichia coli heat-stable enterotoxin 1
      gene and its relationship with fimbrial and enterotoxin genes in E. coli isolated
      from diarrheic piglets.
AB  - A total of 720 Escherichia coli strains isolated from diarrheic piglets on 756
      swine farms were screened for the presence of the enteroaggregative E. coli heat
      stable enterotoxin 1 (EAST1) gene by polymerase chain reaction (PCR). Escherichia
      coli strains that carried EAST1 genes were also tested by PCR for the presence of
      4 fimbriae (F4, F5, F6, F41), 2 heat-stable enterotoxins (STa and STb), and 1
      heat-labile enterotoxin (LT) gene. One hundred sixty-four (22.7%) of the 720 E.
      coli isolates carried genes for EAST1. Of these 164 isolates, 62 (37.8%) carried
      EAST1 genes only, 11 (6.7%) carried genes for at least 1 of the fimbrial
      adhesins, 51 (31.1%) carried genes for at least 1 of the enterotoxins, and 40
      (23.8%) carried genes for at least 1 of the fimbrial adhesins and enterotoxins.
      Forty-six percent of strains that carried EAST1 genes carried STa genes, and 16%
      of strains that carried EAST1 genes carried F4. The isolation rate of
      enterotoxigenic E. coli strains carrying genes for EAST1 gene was 63%. The 6
      major genotypes observed in this study (in decreasing order) were EAST1+,
      EAST1+STa+, EAST1+STa+STb+, EAST1+STa+F5+, EAST1+STa+F4+, and EAST1+STb+F4+.
      EAST1 is widely prevalent among diarrheagenic strains of E. coli and may
      represent an important virulence determinant in the pathogenesis of enteric
      colibacillosis of preweaned pigs.

PMID- 11243359
TI  - Histological and immunohistochemical detection of different Helicobacter species
      in the gastric mucosa of cats.
AB  - Detailed histopathological evaluation of the gastric mucosa of Helicobacter
      infected cats is complicated by the difficulty of recognizing Helicobacter
      organisms on hematoxylin and eosin (HE)-stained sections and the ability of
      multiple Helicobacter species to infect cats. In this study, the presence and
      localization of different species of Helicobacter in the stomachs of cats was
      investigated using silver staining and immunohistochemistry. Five groups
      containing 5 cats each were established (group 1: urease negative and
      Helicobacter free; groups 2, 3, 4, and 5: urease positive and infected with
      Helicobacter heilmannii, unclassified Helicobacter spp., Helicobacter felis, and
      Helicobacter pylori, respectively). Gastric samples were evaluated by HE and
      silver staining and by immunohistochemistry with 3 different anti-Helicobacter
      primary antibodies. Helicobacter were detected by Steiner stain in all infected
      cats at the mucosal surface, in the lumen of gastric glands, and in the cytoplasm
      of parietal cells. In silver-stained sections, H. pylori was easily
      differentiated from H. felis, H. heilmannii, and unclassified Helicobacter spp.,
      which were larger and more tightly coiled. No organisms were seen in uninfected
      cats. Helicobacter antigen paralleled the distribution of organisms observed in
      Steiner-stained sections for 2 of the 3 primary antibodies tested. The antisera
      were not able to discriminate between the different Helicobacter species
      examined. A small amount of Helicobacter antigen was present in the lamina
      propria of 3 H. pylori-, 3 H. felis-, and 1 H. heilmannii-infected cat. Minimal
      mononuclear inflammation was present in uninfected cats and in those infected
      with unclassified Helicobacter spp. and H. heilmannii cats. In H. felis-infected
      cats, lymphoid follicular hyperplasia with mild pangastric mononuclear
      inflammation and eosinophilic infiltrates were present. The H. pylori-infected
      cats had severe lymphoid follicular hyperplasia and mild to moderate mononuclear
      inflammation accompanied by the presence of neutrophils and eosinophils. These
      findings indicate that Steiner staining and immunohistochemistry are useful for
      detecting Helicobacter infections, particularly when different Helicobacter
      species can be present. Monoclonal antibodies specific for the different
      Helicobacter species could be important diagnostic aids. There appear to be
      differences in the severity of gastritis in cats infected with different
      Helicobacter species.

PMID- 11243360
TI  - Detection of chlamydial antibody by fetal serology--an aid to the diagnosis of
      ovine abortion.
AB  - Two serological tests (indirect immunofluorescence and enzyme-linked
      immunosorbent assay) were developed for the detection of fetal antibody to
      Chlamydia psittaci. Fetal blood and thoracic fluid from 126 field cases of
      suspected ovine chlamydial abortion were examined using both tests. Placenta and
      fetal tissues (lung, liver, and kidney) from the same animals were also examined
      by the following conventional diagnostic methods: isolation in McCoy cells,
      detection of chlamydial lipopolysaccharide (LPS), modified Ziehl-Nielsen
      staining, and direct fluorescent antibody staining of chlamydia in frozen
      cryostat sections. Seventy cases were positive by fetal serology, and of these,
      68 were also positive by isolation and/or LPS detection. The remaining 56 cases
      had negative fetal serology, and of these, 39 were positive by isolation and/or
      LPS detection. Results indicate that fetal serology, although less sensitive than
      either isolation in McCoy cells or detection of chlamydial LPS antigen, may be of
      particular use when placenta is not available.

PMID- 11243361
TI  - A comparison of diagnostic assays for the detection of type A swine influenza
      virus from nasal swabs and lungs.
AB  - Nasal swabs and lung samples from pigs experimentally infected with H1N1 swine
      influenza virus (SIV) were examined for the presence of SIV by the indirect
      fluorescent antibody assay, immunohistochemistry, cell culture virus isolation,
      egg inoculation, and 2 human enzyme immunoassays (membrane enzyme immunoassay,
      microwell enzyme immunoassay). Egg inoculation was considered to be the gold
      standard for assay evaluation. The 2 human enzyme immunoassays (EIA) and egg
      inoculation agreed 100% for the prechallenge nasal swabs. Agreement on SIV
      identification in nasal swabs with egg inoculation following challenge was
      considered to be good to excellent for membrane EIA (kappa = 0.85) and microwell
      EIA (kappa = 0.86). Agreement on SIV identification in lung tissue with egg
      inoculation following challenge was good to excellent for membrane EIA (kappa =
      0.75), fair for microwell EIA, fluorescent antibody, and cell culture virus
      isolation (kappa = 0.48, 0.64, 0.62, respectively), and poor for
      immunohistochemistry (kappa = 0.36). No assay was 100% accurate, including the
      "gold standard," egg inoculation. In light of this information, it is important
      to consider clinical signs of disease and a thorough herd history in conjunction
      with diagnostic results to make a diagnosis of SIV infection.

PMID- 11243362
TI  - Maximal predicted duration of viremia in bluetongue virus-infected cattle.
AB  - Central to the development of rational trade policies pertaining to bluetongue
      virus (BTV) infection is determination of the risk posed by ruminants previously
      exposed to the virus. Precise determination of the maximal duration of infectious
      viremia is essential to the development of an appropriate quarantine period prior
      to movement of animals from BTV-endemic to BTV-free regions. The objective of
      this study was to predict the duration of detectable viremia in BTV-infected
      cattle using a probabilistic modeling analysis of existing data. Data on the
      duration of detectable viremia in cattle were obtained from previously published
      studies. Data sets were created from a large field study of naturally infected
      cattle in Australia and from experimental infections of cattle with Australian
      and US serotypes of BTV. Probability distributions were fitted to the pooled
      empirical data, and the 3 probability distributions that provided the best fit to
      the data were the gamma, Weibull, and lognormal probability distributions. These
      asymmetric probability distributions are often well suited for decay processes,
      such as the time to termination of detectable viremia. The analyses indicated a >
      99% probability of detectable BTV viremia ceasing after < or = 9 weeks of
      infection in adult cattle and after a slightly longer interval in BTV-infected,
      colostrum-deprived newborn calves.

PMID- 11243363
TI  - Application of single-strand conformation polymorphism to the study of bovine
      viral diarrhea virus isolates.
AB  - Single-strand conformation polymorphism (SSCP) analysis of polymerase chain
      reaction (PCR) products is a genetic screening technique for rapid detection of
      nucleotide substitutions in PCR-amplified genomic DNA or cDNA. It is based on the
      observation that partially formamide-denatured double-stranded DNA migrates as 2
      single-stranded DNA molecules when electrophoresed in nondenaturing
      polyacrylamide gels. The mobility depends on the 3-dimensional conformation of
      the strand under the conditions used. It is possible to discriminate between DNA
      strands differing in only 1 nucleotide. The method was applied to the analysis of
      Bovine Viral Diarrhea Virus (BVDV) isolates. Reference and Argentinian strains
      were assessed for variations in their 5' untranslated region (5'-UTR). The PCR
      products of the 5'-UTR ends were formamide denatured and compared by SSCP
      analysis in nondenaturing 15% polyacrylamide and 15% polyacrilamide-5% glycerol
      gels. The reference strains SD-1, Singer, and Oregon C24V had differences in
      electrophoretic patterns. Despite the high conservation among the 5'-UTR of
      pestiviruses, the method allowed discrimination among all 9 Argentinian isolates.
      The 5'-UTR of a fetal kidney-derived isolate (1R93) was PCR amplified and cloned
      in a plasmid vector; the SSCP analysis of 30 PCR products obtained by direct
      amplification over randomly selected clones produced 5 different banding
      patterns, indicating the existence of viral quasispecies. The results show that
      SSCP may be used to identify and differentiate among BVDV isolates.

PMID- 11243364
TI  - Tissue distribution and genetic typing of porcine circoviruses in pigs with
      naturally occurring congenital tremors.
AB  - Congenital tremors (CT) type A2 is associated with porcine circovirus (PCV) and
      deficient and abnormal myelin. The aim of this study was to determine the tissue
      distribution and genetic type of PCV in 1-2-day-old pigs with naturally occurring
      CT type A2 using in situ hybridization, polymerase chain reaction (PCR), and
      indirect fluorescent antibody tests on frozen tissue sections. CT-affected and
      clinically normal pigs were selected from 4 farms in the midwestern USA that were
      undergoing outbreaks of CT type A2. All CT and most normal pigs were infected
      with PCV. PCV was widely distributed in tissues of infected pigs and was most
      common in tissues of the central nervous system and liver. In all infected pigs,
      there were more PCV-infected cells in brain and spinal cord than in nonneural
      tissues. CT pigs had many more PCV-infected cells in the brain and spinal cord
      than did clinically normal pigs because of a more diffuse distribution and a
      larger proportion of infected cells. The cells most commonly infected with PCV in
      brain and spinal cord were large neurons. In nonneural tissues, macrophages were
      the most frequent cell type infected. PCR analysis demonstrated only PCV type 2
      and not PCV type 1 in all PCV-infected pigs on all 4 farms.

PMID- 11243365
TI  - Incidence of polysaccharide storage myopathy in draft horse-related breeds: a
      necropsy study of 37 horses and a mule.
AB  - Skeletal muscle samples from 38 draft horse-related animals 1-23 years of age
      were evaluated for evidence of aggregates of glycogen and complex polysaccharide
      characteristic of equine polysaccharide storage myopathy (EPSSM). Cardiac muscle
      from 12 of these horses was also examined. Antemortem serum levels of creatine
      kinase (CK) and aspartate aminotransferase (AST) from 9 horses with EPSSM and 5
      horses without EPSSM were compared. Skeletal muscle from 17 horses contained
      inclusions of periodic acid-Schiff (PAS)-positive, amylase-resistant complex
      polysaccharide. Similar inclusions were also present in the cardiac muscle of 1
      horse. A vacuolar myopathy with aggregates of PAS-positive, amylase-sensitive
      glycogen was seen in 8 other horses, and these findings are also considered
      diagnostic for EPSSM. Antemortem serum activities of CK and AST were often higher
      in EPSSM horses than in horses without EPSSM. Using the presence of amylase
      resistant complex polysaccharide as the criterion for diagnosis of EPSSM, the
      incidence in this population was 45%. Inclusion of horses with aggregates of
      glycogen but no amylase-resistant complex polysaccharide as representative of the
      range of pathologic findings in horses with EPSSM resulted in a 66% incidence in
      this population.

PMID- 11243366
TI  - Double in situ hybridization for simultaneous detection of porcine reproductive
      and respiratory syndrome virus (PRRSV) and porcine circovirus (PCV).
AB  - A double in situ hybridization method for the simultaneous detection of porcine
      reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus (PCV)
      genomes in the same tissue section was applied to lung tissues from 9 pigs in
      which PRRSV and PCV coinfection had been previously demonstrated. Paraffin
      embedded tissue sections were simultaneously hybridized with a digoxigenin
      labeled antisense RNA probe for PRRSV and a fluorescein-labeled antisense RNA
      probe for PCV, and hybridization was detected with anti-digoxigenin alkaline
      phosphatase/fast red and anti-fluorescein peroxidase/diaminobenzidine,
      respectively. PRRSV and PCV genomes were identified in the same pulmonary cell
      types as reported previously in all 9 pigs. In all pigs, PCV-positive cells
      outnumbered PRRSV-positive cells. A small proportion of alveolar macrophages
      contained both PRRSV and PCV genomes.

PMID- 11243367
TI  - Usefulness of a commercially available enzyme immunoassay for Shiga-like toxins I
      and II as a presumptive test for the detection of Escherichia coli O157:H7 in
      cattle feces.
AB  - The performance of a commercially available enzyme immunoassay (EIA) for
      determining the presence of Shiga toxin I and II in human diarrheal stool samples
      was evaluated for use as a presumptive test for the presence of Escherichia coli
      O157:H7 in nondiarrheal bovine fecal samples collected from 10 Kansas cow-calf
      ranches. The prevalence of E. coli O157:H7 in 2,297 samples, as determined by
      selective bacterial culture, was 1.6%. The sample prevalence of non-E. coli
      O157:H7 Shiga toxin-producing bacteria, as detected by the Shiga toxin EIA, was
      5.8%. Only 2 of 136 samples that tested positive with the Shiga toxin EIA were
      positive for E. coli O157:H7 by culture. Compared with bacterial culture, the
      sensitivity of the Shiga toxin EIA was 5.5% and the specificity was 94.1%.
      Agreement between the 2 tests, as measured by the kappa statistic, was poor
      (kappa = -0.002). Although the Shiga toxin EIA was not a good presumptive test
      for the determination of E. coli O157:H7 in bovine fecal samples because of its
      low sensitivity (5.5%), it might be a useful test for the detection of Shiga
      toxin producing non-E. coli O157:H7 organisms in bovine feces.

PMID- 11243368
TI  - Pulmonary botryomycosis in a Scottish highland steer.
AB  - Pertinent necropsy findings in a 5 1/2-year-old Scottish Highland steer with
      chronic intractable pneumonia and cough were limited to the pulmonary system. The
      accessory lobe of the lung was collapsed, scarred, and multifocally adhered to
      parietal pleura. A polypoid mass almost completely obstructed the lobar bronchus
      and protruded into the trachea; mucopurulent exudate distended more distal
      bronchi. Botryomycosis was diagnosed when histologic examination revealed
      pyogranulomatous pneumonia with eosinophilic granules and "club" formation
      surrounding colonies of gram-positive cocci. Staphylococcus aureus was cultured
      from the lung. Botryomycosis is an unusual response to infection with common
      bacteria and is characterized by pyogranulomatous inflammation with formation of
      eosinophilic granules surrounding colonies of gram-positive cocci or gram
      negative bacilli. Among domestic species, staphylococcal botryomycosis is most
      common as a wound infection in horses or as mastitis in cows and sows. Pulmonary
      botryomycosis is rare in horses, humans, and guinea pigs and apparently has not
      been reported in cattle.

PMID- 11243369
TI  - Prevalence of psammoma bodies in meninges and choroid plexuses of raccoons
      (Procyon lotor) from Parramore Island, Virginia.
AB  - Microscopic evidence of multifocal mineralizations (psammoma bodies) were seen in
      brains of 33/53 (62%) raccoons (Procyon lotor) necropsied on Parramore Island,
      Virginia. Most mineralized foci had concentric laminations and were present in
      small capillaries of meninges of the brain (15/33), in choroid plexus (3/33), or
      at both these sites (13/33). In 2 raccoons, the lesions were confined to the
      meninges of the proximal cervical spinal cord. In most cases, the affected
      vessels appeared to have been completely occluded. However, no evidence of
      ischemic changes in the brain parenchyma was seen, and none of the raccoons had
      abnormal neurologic signs prior to euthanasia. The condition appears to be a
      common incidental histopathologic finding in raccoons from the eastern United
      States. Although the exact cause of this condition is not known, a primary
      vascular insult with resultant dystrophic mineralization of the affected vessels
      is suspected.

PMID- 11243370
TI  - Sensitivity and specificity of the complement fixation test for detection of
      cattle persistently infected with Anaplasma marginale.
AB  - The complement fixation (CF) test commonly is used to identify cattle infected
      with Anaplasma marginale prior to interstate or international movement. Estimates
      of the accuracy of the CF test in detecting animals persistently infected with A.
      marginale vary widely. In this study, the sensitivity and specificity of the CF
      test for detection of carrier animals was determined using serum from 232 cattle
      previously defined as A. marginale positive or negative by nested polymerase
      chain reaction methods and hybridization. Considering results from 2 independent
      laboratories and interpreting a 1:5 suspect reaction as positive, the best
      estimate of CF test sensitivity was 20%, with a specificity of 98%. Using a 1:10
      cutoff, sensitivity decreased to 14% and specificity increased to 99%. Results of
      this study indicate that the CF test is ineffective for identifying cattle
      persistently infected with A. marginale and thus is inadequate for anaplasmosis
      regulatory and surveillance programs.

PMID- 11243372
TI  - An enzyme-linked immunosorbent assay for the convenient serodiagnosis of
      contagious equine metritis in mares.
AB  - An enzyme-linked immunosorbent assay (ELISA) was developed for the serodiagnosis
      of contagious equine metritis (CEM), a sexually transmitted disease caused by
      Taylorella equigenitalis. Antigen preparation was simple, and antigens derived
      from both classical and atypical forms of T. equigenitalis enabled detection of
      antibody responses elicted in horses experimentally exposed to either form of the
      bacterium. Sera serially obtained from these horses from 0 to 63 days
      postexposure were tested by the traditional complement fixation test (CFT) for
      CEM and with the ELISA, using both antigens separately. There was close agreement
      between CFT and ELISA methodologies during the postexposure time period used to
      detect CEM serodiagnostically in regulatory animal health testing programs.
      Unlike the CFT, which requires an overnight incubation step, the ELISAs are more
      convenient and can be completed in 3 hours.

PMID- 11243371
TI  - A disease resembling inclusion body disease of boid snakes in captive palm vipers
      (Bothriechis marchi).
AB  - Between April 1998 and June 1999, 8 palm vipers (Bothriechis marchi) were
      diagnosed with a disease similar to inclusion body disease (IBD) of boids. Six
      palm vipers were captive bred, and 2 were wild caught. All of the vipers were
      adults at the time of death. Three palm vipers were found dead with no
      premonitory clinical signs, and 5 had anorexia plus possibly 1 of the following
      clinical signs: regurgitation, paresis, and dehydration. Histologically, all
      snakes had intracytoplasmic, round to oval, single to multiple eosinophilic
      inclusion bodies in hepatocytes and renal tubular epithelial cells. Inclusion
      bodies were distributed among other organs with varying frequency. Common
      concurrent histologic lesions were urate nephrosis, septic thrombi, and
      hepatocellular degeneration. Ultrastructurally, inclusions had features similar
      to inclusions in boid snakes with IBD.

PMID- 11243373
TI  - Immunohistochemical detection of scrapie prion proteins in clinically normal
      sheep in Pennsylvania.
AB  - Following diagnosis of scrapie in a clinically suspect Suffolk sheep, 7
      clinically normal flockmates were purchased by the Pennsylvania Department of
      Agriculture to determine their scrapie status using an immunohistochemical
      procedure. Two of the 7 euthanized healthy sheep had positive immunohistochemical
      staining of the prion protein of scrapie (PrP-Sc) in their brains, nictitating
      membranes, and tonsils. The PrP-Sc was localized in the areas of the brain where,
      histopathologically, there was neurodegeneration and astrocytosis. The PrP-Sc
      occurred within germinal centers of the affected nictitating membranes and
      tonsils and was located in the cytoplasm of the dendrite-like cells, lymphoid
      cells, and macrophages. These results confirm that immunohistochemical
      examination of the nictitating membrane can be used as a screen for the presence
      of scrapie infection in clinically normal sheep at a capable veterinary
      diagnostic laboratory. In sheep with a PrP-Sc-positive nictitating membrane, the
      diagnosis of scrapie should be confirmed by histopathology and
      immunohistochemical examination of the brain following necropsy. Following full
      validation, immunohistochemistry assays for detection of PrP-Sc in nictitating
      membrane lymphoid tissues can improve the effectiveness of the scrapie control
      and eradication program by allowing diagnosis of the disease in sheep before the
      appearance of clinical signs.

PMID- 11243374
TI  - Preliminary findings on the experimental transmission of chronic wasting disease
      agent of mule deer to cattle.
AB  - To determine the transmissibility of chronic wasting disease (CWD) to cattle and
      to provide information about clinical course, lesions, and suitability of
      currently used diagnostic procedures for detection of CWD in cattle, 13 calves
      were inoculated intracerebrally with brain suspension from mule deer naturally
      affected with CWD. Between 24 and 27 months postinoculation, 3 animals became
      recumbent and were euthanized. Gross necropsies revealed emaciation in 2 animals
      and a large pulmonary abscess in the third. Brains were examined for protease
      resistant prion protein (PrP(res)) by immunohistochemistry and Western blotting
      and for scrapie-associated fibrils (SAFs) by negative-stain electron microscopy.
      Microscopic lesions in the brain were subtle in 2 animals and absent in the third
      case. However, all 3 animals were positive for PrP(res) by immunohistochemistry
      and Western blot, and SAFs were detected in 2 of the animals. An uninoculated
      control animal euthanized during the same period did not have PrP(res) in its
      brain. These are preliminary observations from a currently in-progress
      experiment. Three years after the CWD challenge, the 10 remaining inoculated
      cattle are alive and apparently healthy. These preliminary findings demonstrate
      that diagnostic techniques currently used for bovine spongiform encephalopathy
      (BSE) surveillance would also detect CWD in cattle should it occur naturally.

PMID- 11243375
TI  - Development of cyclin-dependent kinase modulators as novel therapeutic approaches
      for hematological malignancies.
AB  - The majority of hematopoietic malignancies have aberrancies in the retinoblastoma
      (Rb) pathway. Loss in Rb function is, in most cases, a result of the
      phosphorylation and inactivation of Rb by the cyclin-dependent kinases (cdks),
      main regulators of cell cycle progression. Flavopiridol, the first cdk modulator
      tested in clinical trials, is a flavonoid that inhibits several cdks with
      evidence of cell cycle block. Other interesting preclinical features are the
      induction of apoptosis, promotion of differentiation, inhibition of angiogenic
      processes and modulation of transcriptional events. Initial clinical trials with
      infusional flavopiridol demonstrated activity in some patients with non-Hodgkin's
      lymphoma, renal, prostate, colon and gastric carcinomas. Main side-effects were
      secretory diarrhea and a pro-inflammatory syndrome associated with hypotension.
      Phase 2 trials with infusional flavopiridol in CLL and mantle cell lymphoma,
      other schedules and combination with standard chemotherapies are ongoing. The
      second cdk modulator tested in clinical trials, UCN-01, is a potent protein
      kinase C inhibitor that inhibits cdk activity in vitro as well. UCN-01 blocks
      cell cycle progression and promotes apoptosis in hematopoietic models. Moreover,
      UCN-01 is able to abrogate checkpoints induced by genotoxic stress due to
      modulation in chk1 kinase. The first clinical trial of UCN-01 demonstrated very
      prolonged half-life (approximately 600 h), 100 times longer than the half-life
      observed in preclinical models. This effect is due to high binding affinity of
      UCN-01 to the human plasma protein alpha-1-acid glycoprotein. Main side-effects
      in this trial were headaches, nausea/vomiting, hypoxemia and hyperglycemia.
      Clinical activity was observed in patients with melanoma, non-Hodgkin's lymphoma
      and leiomyosarcoma. Of interest, a patient with anaplastic large cell lymphoma
      refractory to high-dose chemotherapy showed no evidence of disease after 3 years
      of UCN-01 therapy. Trials of infusional UCN-01 in combination with Ara-C or
      gemcitabine in patients with acute leukemia and CLL, respectively, have
      commenced. In conclusion, flavopiridol and UCN-01 are cdk modulators that reach
      biologically active concentrations effective in modulating CDK in vitro, and show
      encouraging results in early clinical trials in patients with refractory
      hematopoietic malignancies. Although important questions remain to be answered,
      these positive experiences will hopefully increase the therapeutic modalities in
      hematological malignancies.

PMID- 11243376
TI  - Hypothesis: phenol and hydroquinone derived mainly from diet and gastrointestinal
      flora activity are causal factors in leukemia.
AB  - High background levels of phenol and hydroquinone are present in the blood and
      urine of virtually all individuals, but vary widely. Phenol and hydroquinone have
      been strongly implicated in producing leukemia associated with benzene exposure,
      because they reproduce the hematotoxicity of benzene, cause DNA and chromosomal
      damage found in leukemia, inhibit topoisomerase II, and alter hematopoiesis and
      clonal selection. The widely varying background levels of phenol and hydroquinone
      in control individuals stem mainly from direct dietary ingestion, catabolism of
      tyrosine and other substrates by gut bacteria, ingestion of arbutin-containing
      foods, cigarette smoking, and the use of some over-the-counter medicines. We
      hypothesize that these background sources of phenol and hydroquinone and
      associated adducts play a causal role in producing some forms of de novo leukemia
      in the general population. This hypothesis is consistent with recent
      epidemiological findings associating leukemia with diets rich in meat and
      protein, the use of antibiotics (which change gastrointestinal flora make-up),
      lack of breastfeeding, and low activity of NAD(P)H quinone oxidoreductase which
      detoxifies quinones derived from phenol and hydroquinone and protects against
      benzene hematotoxicity. An attractive feature of our hypothesis is that it may
      explain why many people who have no known occupational exposures or significant
      smoking history develop leukemia. The hypothesis predicts that susceptibility to
      the disease would be related to diet, medicinal intake, genetics and gut-flora
      composition. The latter two of these are largely beyond our control, and thus
      dietary modification and reduced use of medicines that elevate phenol levels may
      be the best intervention strategies for lowering leukemia risk.

PMID- 11243377
TI  - C/EBPepsilon -/- mice: increased rate of myeloid proliferation and apoptosis.
AB  - CCAAT/enhancer binding protein epsilon (C/EBPepsilon) is essential for terminal
      granulocytic differentiation. Its expression begins at the transition between the
      proliferative and non-proliferative compartments of myelopoiesis. We studied the
      effect of targeted disruption of the C/EBPepsilon gene on murine myeloid
      proliferation and apoptosis. Bone marrow cellularity of C/EBPepsilon -/- and wild
      type mice was 95% and 65%, respectively. The C/EBPepsilon -/- mice had an
      expansion in the number of their CFU-GM/femur. The number of myeloid committed
      progenitor cells in the peripheral blood and the spleen of these mice was also
      increased. Bromodeoxyuridine (BrDU) pulse labeling studies demonstrated that the
      fraction of actively proliferating cells was two-fold higher in the bone marrow
      of C/EBPepsilon -/- mice. However, the number of myeloid colonies arising from
      purified Sca-1+/lin- early hematopoietic progenitor cells and from bone marrow
      mononuclear cells grown in different cytokine combinations was not significantly
      different between wild-type and knock-out mice. Also, long-term marrow growth,
      and CFU were not different between the wild-type and C/EBPepsilon -/- mice. The
      sensitivity to induction of apoptosis in the committed progenitor cell
      compartment after either withdrawal of growth factor or brief exposure to
      etoposide was normal. However, Gr-1 antigen-positive C/EBPepsilon -/-
      granulocytic cells showed an increased rate of apoptosis in comparison to their
      wild-type counterparts. In summary, the myeloid compartment appears to be
      expanded in mice lacking C/EBPepsilon. However, this is not the consequence of an
      intrinsic myeloproliferation but due to an indirect, possibly cytokine-mediated
      stimulation of myelopoiesis in vivo. C/EBPepsilon may have a role in the
      inhibition of apoptosis in maturing granulocytic cells.

PMID- 11243378
TI  - The inositol 5-phosphatase SHIP is expressed as 145 and 135 kDa proteins in blood
      and bone marrow cells in vivo, whereas carboxyl-truncated forms of SHIP are
      generated by proteolytic cleavage in vitro.
AB  - The inositol polyphosphate 5-phosphatase SHIP plays an important role in negative
      signalling in B cells and mast cells and in the down-regulation of cytokine
      receptor-mediated signals in myeloid cells. SHIP is expressed as a 145 kDa full
      length protein and an isoform of 135 kDa due to alternative splicing. Additional
      smaller forms of SHIP which are truncated at the carboxy terminus have been
      described in bone marrow and peripheral blood mononuclear cells (PBMC). Our data
      demonstrate that human bone marrow cells and PBMC from healthy donors and
      patients with acute myeloid leukemia express the 145 kDa form of SHIP and low
      amounts of a 135 kDa form of SHIP in vivo whereas C-terminal-truncated SHIP
      proteins are generated by a PMSF-sensitive protease during the preparation of
      cell lysates in vitro. We have further characterized this protease and identified
      a proteolytic cleavage site in the human SHIP protein C-terminal to tryptophan
      residue 941. These data support a physiological role for the 145 and 135 kDa
      forms of SHIP in bone marrow and peripheral blood cells from normal donors and
      patients with acute myeloid leukemia.

PMID- 11243379
TI  - Immunoglobulin lambda isotype gene rearrangements in B cell malignancies.
AB  - The human immunoglobulin lambda (IGL) locus contains seven J-Clambda gene regions
      of which only J-Clambda1, J-Clambda2 J-CA3 and J-Clambda7 encode the four
      Iglambda isotypes, ie Mcg, Ke-Oz-, Ke-Oz+, and Mcp, respectively. We used isotype
      specific DNA probes for detection of IGL gene rearrangements in 212 B cell
      malignancies: 76 precursor B cell acute lymphoblastic leukemias (precursor B
      ALL), 74 Iglambda+ chronic B cell leukemias (CBL), 34 Iglambda+ non-Hodgkin
      lymphomas (B-NHL), and 28 Iglambda+ multiple myelomas (MM). The J-Clambda3 gene
      region was most frequently involved (50%), followed by J-Clambda2 (38%) and J
      Clambda1 (9%). There was no involvement of the J-Clambda4 and J-Clambda5 gene
      regions. Rearrangements to J-Clambda6 (n= 4) were exclusively found in precursor
      B-ALL (19% of all IGL rearrangements in precursor B-ALL) and only a single J
      Clambda7 recombination was detected in an Iglambda+ B-NHL. In the group of
      Iglambda+ malignancies, a significant shift was observed from predominant J
      Clambda3 usage (54%) in mature surface Iglambda+ malignancies (CBL and B-NHL) to
      60% J-Clambda2 usage in Iglambda+ secreting MM. The distribution of IGL isotype
      rearrangements found in MM resembled the Iglambda isotype protein expression
      reported in MM patients. Based on these extensive Southern blot data, we suggest
      that a rapid and efficient detection of clonal IGL gene rearrangements can be
      obtained when a single Bg/II digest is used in combination with the IGLJ2 probe,
      which detects clonality in >95% of cases with an Iglambda+ malignancy. Higher
      percentages (>98%) can be reached by including a second digest (HindIII) that
      reduces the chance of comigration of rearranged and germline bands. In case of
      precursor B-ALL we recommend including the IGLJ6 probe for the detection of
      rearrangements to J-Clambda6.

PMID- 11243380
TI  - HLA class I antigen cell surface expression is preserved on acute myeloid
      leukemia blasts at diagnosis and at relapse.
AB  - Human leukocyte antigens (HLA) class I molecules restrict the interaction between
      cytotoxic T cells and target cells. Abnormalities in HLA class I antigen
      expression and/or function may provide tumor cells with a mechanism for escaping
      immune surveillance and resisting T cell-based immunotherapies. The potential for
      applying T cell-based immunotherapy in the treatment of acute myeloid leukemia
      (AML) has stimulated interest in analyzing HLA class I antigen expression on
      leukemic blasts in this disease. Little information is available in the
      literature. We have analyzed HLA class I antigen expression on bone marrow
      samples from 25 newly diagnosed AML patients by indirect immunofluorescence
      staining with monoclonal antibodies. Five of these patients were also studied at
      relapse. Leukemic blasts were resolved from normal lymphocytes by staining with
      antiCD45 antibody; CD45 expression is dim on leukemia cells, but bright on
      lymphocytes. HLA class I antigen expression was higher on leukemic blasts than on
      autologous lymphocytes in all but one case. Moreover, there was no significant
      change in HLA class I antigen expression at relapse. These results suggest that
      abnormalities in HLA class I antigens are infrequent in AML and should not
      represent a major obstacle to the application of T cell-based immunotherapies in
      this disease.

PMID- 11243381
TI  - Quantification of minimal residual disease in children with oligoclonal B
      precursor acute lymphoblastic leukemia indicates that the clones that grow out
      during relapse already have the slowest rate of reduction during induction
      therapy.
AB  - Antigen receptor gene rearrangements are applied for the PCR-based minimal
      residual disease (MRD) detection in acute lymphoblastic leukemia (ALL). It is
      known that ongoing rearrangements result in subclone formation, and that the
      relapsing subclone(s) can contain antigen receptor rearrangement(s) that differ
      from the rearrangements found in the major clone(s) at diagnosis. However, the
      mechanism leading to this so-called clonal evolution is not known, particularly
      at which time point in the disease the relapsing subclone obtains its (relative)
      therapy resistance. To obtain insight in clonal evolution, we followed the
      kinetics of several subclones in three oligoclonal ALL patients during induction
      therapy. Clone-specific nested PCR for immunoglobulin heavy chain or T cell
      receptor delta gene rearrangements were performed in limiting dilution assays on
      bone marrow samples taken at diagnosis, at the end of induction therapy and at
      possible relapse in three children with oligoclonal B-precursor ALL. We
      demonstrated that in all three patients the subclones were behaving differently
      in response to therapy. Moreover, in the two patients who relapsed, the clones
      that grew out during relapse showed the slowest regression or even evoluated
      during induction therapy and the clones that were not present at relapse showed
      good response to induction therapy. These results support the hypothesis that at
      least in some patients already at diagnosis or in the very first weeks, subclones
      have important differences in respect to resistance. Hence, these data give
      experimental evidence for the need to develop, during the first months after
      diagnosis, quantitative PCR assays for at least two different Ig/TCR gene
      rearrangement targets for every ALL patient.

PMID- 11243383
TI  - Establishment of a follicular lymphoma cell line (FLK-1) dependent on follicular
      dendritic cell-like cell line HK.
AB  - A novel cell line, FLK-1, was established from bone marrow cells of a patient
      with follicular lymphoma by means of co-culture with follicular dendritic cell
      (FDC)-like cell line HK. Immunophenotypic analysis showed that FLK-1 expressed
      CD10, CD19, CD20, CD38, IgG and HLA-DR, which is a typical feature of germinal
      center B cells. Cytogenetic analysis of FLK-1 demonstrated t(14;18)(q32;q21)
      translocation involving BCL2 and immunoglobulin heavy chain genes. Especially
      noteworthy is that the growth of FLK-1 was found to be dependent on a FDC line,
      HK. When HK cells were removed from the culture, FLK-1 cells stopped growing and
      eventually died. An apoptotic mechanism appeared to be involved as indicated by
      the presence of chromosome condensation and DNA ladder formation. The culture
      experiment using micropore membranes showed that soluble factor(s) of HK cells
      supported the growth, while direct cell-to-cell contact appeared to be necessary
      for longterm cell proliferation. These findings suggest the importance of the
      micro-environment for follicular lymphoma cells to grow. The FLK-1 cell line may
      thus prove to be useful for studying the growth mechanism of follicular lymphoma
      and provide new insights into the pathogenesis of follicular lymphoma.

PMID- 11243382
TI  - Development and characterization of T cell leukemia cell lines established from
      SCL/LMO1 double transgenic mice.
AB  - We have established a panel of nine immortal cell lines from T cell malignancies
      which arose in mice transgenic for the SCL and LMO1 genes. Cells from the primary
      malignancies initially grew very slowly in vitro, loosely attached to a stromal
      layer, before gaining the ability to proliferate independently. Upon gaining the
      ability to proliferate in the absence of a stromal layer, these cell lines grew
      rapidly, doubling every 14-23 h, to a very high density, approaching 10(7)
      cells/ml. Whereas the tumors which arise in SCL/LMO1 double transgenic mice are
      typically diploid or pseudodiploid, the cell lines were all grossly aneuploid,
      suggesting the possibility that additional genetic events were selected for in
      vitro. Given that SCL and LMO1 gene activation are both commonly seen in human
      patients with T cell acute lymphoblastic leukemia, these cell lines may be a
      useful in vitro model for the human disease.

PMID- 11243384
TI  - Hypermethylation of p16INK4A gene promoter during the progression of plasma cell
      dyscrasia.
AB  - Recent studies have indicated a close relationship between inactivation of tumor
      suppressor genes (TSGs) and disease progression. The genes encoding the cyclin
      dependent kinase inhibitors p16INK4A and p15INK4B are potent TSGs, and
      correlations between their inactivation and disease progression have also been
      reported in various malignancies. In this study, we analyzed the methylation
      status of p16INK4A and p15INK4B gene promoters in plasma cell dyscrasias (PCDs)
      by methylation-specific PCR (MSP). In analyses using DNAs extracted from bone
      marrow mononuclear cells (BM-MNCs), patients with multiple myeloma (MM) showed
      frequent hypermethylation of the p16INK4A gene (15/37, 41%), whereas p15INK4B
      gene methylation was not so frequent (5/37, 14%). Many patients whose BM-MNC
      showed dense methylation of the p16INK4A gene had extramedullary plasmacytoma
      (extra-PC), and all available extra-PC samples showed alterations of the p16INK4A
      gene (4; dense methylation, 1; homozygous deletion). In contrast to MM,
      hypermethylation of the p16INK4A gene was significantly infrequent in indolent
      PCDs (2/22, 9%, P= 0.0055). The infrequency in indolent PCDs was also confirmed
      by analyses using DNAs extracted from BM smears (1/29, 3%). It is possible that
      hypermethylation of the p16INK4A gene promoter contributes to progression to
      aggressive MM from indolent PCD, especially to extra-PC development.

PMID- 11243386
TI  - Angiogenesis in multiple myeloma: correlation between in vitro endothelial
      colonies growth (CFU-En) and clinical-biological features.
AB  - Mouse models and studies performed on fixed bone marrow (BM) specimens obtained
      from patients with multiple myeloma (MM) suggest that plasma cell growth is
      dependent on endothelial cell (EC) proliferation within the BM microenvironment.
      In order to assess whether EC overgrowth in MM reflects a spontaneous in vitro
      angiogenesis, BM mononucleated cells from 13 untreated (UT) MM, 20 treated (11
      with melphalan and nine with DAV schedule) MM, eight patients with monoclonal
      gammopathy of uncertain significance (MGUS) and eight controls were seeded in an
      unselective medium to assess EC proliferation. Furthermore, the influence of IL6
      on the EC growth was investigated. Endothelial colonies (CFU-En) appeared as
      small clusters, formed by at least 100 slightly elongated and sometimes bi
      nucleated cells expressing factor VIII, CD31 and CD105 (endoglin). The CFU-En
      mean number/10(6) BM mononucleated cells in untreated MM samples (2.07 s.d. +/-
      1.3) was significantly higher than in normal BM (0.28 +/- 0.48), while no
      difference was seen between normal BM and MGUS (0.28 +/- 0.54). Interestingly,
      the mean number of CFU-En in the DAV group (1.88 +/- 1.6) did not differ from the
      UT, while it was found to be lower in the melphalan group (0.31 +/- 0.63). The
      addition of anti-IL6 monoclonal antibody induced a reduction of both the plasma
      cells in the supernatant and the CFU-En number. This study describes a rapid and
      feasible assay providing support for the association between EC and plasma cells
      further suggesting that the in vitro angiogenesis process may parallel that
      observed in vivo.

PMID- 11243385
TI  - Quantification of minimal residual disease in T-lineage acute lymphoblastic
      leukemia with the TAL-1 deletion using a standardized real-time PCR assay.
AB  - Hematologic relapse remains the greatest obstacle to the cure of children with
      acute lymphoblastic leukemia (ALL). Recent studies have shown that patients with
      increased risk of relapse can be identified by measuring residual leukemic cells,
      called minimal residual disease (MRD), during clinical remission. Current PCR
      methods, however, for measuring MRD are cumbersome and time-consuming. To improve
      and simplify MRD assessment, we developed a real-time quantitative PCR (RQ-PCR)
      assay for detection of leukemic cells that harbor the TAL-1 deletion. We studied
      serial dilutions of leukemic DNA and found the assay had a sensitivity of
      detection of one leukemic cell among 100,000 normal cells. We then investigated
      23 samples from eight children with ALL in clinical remission. We quantified
      residual leukemic cells by using the TAL-1 RQ-PCR assay and by using limiting
      dilution analysis. In 17 samples, both methods detected MRD levels > or =0.001%.
      The percentages of leukemic cells measured by the two methods correlated well (r2
      = 0.926). In the remaining six samples, both methods detected fewer than 0.001%
      leukemic cells. We conclude the TAL-1 RQ-PCR assay can be used for rapid,
      sensitive and accurate assessment of MRD in T-lineage ALL with the TAL-1
      deletion.

PMID- 11243387
TI  - Detection of secondary genetic aberrations in follicle center cell derived
      lymphomas: assessment of the reliability of comparative genomic hybridization and
      standard chromosome analysis.
AB  - Secondary chromosomal aberrations in follicle center cell derived lymphomas
      (FCDL) usually involve gains and losses of genetic material and may be an
      important prognostic value. In the present study, we aimed to determine the power
      of comparative genomic hybridization (CGH) as compared to standard chromosome
      analysis (CA) to detect such secondary aberrations. The same lymph node cell
      suspensions prepared from 30 patients with FCDL were analyzed in parallel by CGH
      and CA based on R banding. In all, 73 discrepancies were found. Sixty-two
      imbalances were detected only by CA and 11 only by CGH. In cases with completely
      resolved karyotypes (n= 17), the median number of discrepancies between CGH and
      CA was one. However, when the karyotype was partially resolved (n = 12), the
      median was four (P < 0.01). Discrepant results were further studied by
      fluorescence in situ hybridization using locus-specific probes. These data
      confirm, that not only for the detection of balanced aberrations, but also for
      the detection of unbalanced aberrations in FCDL, standard chromosome analysis is
      still the 'gold standard'. In contrast, CGH is useful to detect chromosomal
      imbalances when no metaphases are found or no fresh material is available.

PMID- 11243388
TI  - The natural history and clinico-pathological features of the variant form of
      hairy cell leukemia.

PMID- 11243389
TI  - Severe thrombocytopenia and clinical bleeding associated with rituximab infusion
      in a lymphoma patient with massive splenomegaly without leukemic invasion.

PMID- 11243390
TI  - Remission of severe cold agglutinin disease after Rituximab therapy.

PMID- 11243391
TI  - Age cohort subgroups in adult acute myeloid leukaemia studies--the population
      perspective.

PMID- 11243392
TI  - CD13/aminopeptidase N involvement in dendritic cell maturation.

PMID- 11243393
TI  - Deletion of the multidrug resistance protein 1 (MRP1) gene in acute myeloid
      leukemia patients with inversion 16: expression of MRP1 homologues.

PMID- 11243394
TI  - Is HLA-DR4 or the HLA-DRB1*0402 allele associated with decreased risk for CML?

PMID- 11243395
TI  - Molecular signals in anti-apoptotic survival pathways.
AB  - Drug resistance, to date, has primarily been attributed to increased drug export
      or detoxification mechanisms. Despite correlations between drug export and drug
      resistance, it is increasingly apparent that such mechanisms cannot fully account
      for chemoresistance in neoplasia. It is now widely accepted that chemotherapeutic
      drugs kill tumour cells by inducing apoptosis, a genetically regulated cell death
      programme. Evidence is emerging that the exploitation of survival pathways, which
      may have contributed to disease development in the first instance, may also be
      important in the development of the chemoresistance. This review discusses the
      components of and associations between multiple signalling cascades and their
      possible contribution to the development of neoplasia and the chemoresistant
      phenotype.

PMID- 11243396
TI  - Chronic neutrophilic leukemia (CNL): a clinical, pathologic and cytogenetic
      study.
AB  - This report describes a single institution's recent experience with six patients
      fulfilling the diagnostic criteria of chronic neutrophilic leukemia. No patient
      had the Philadelphia chromosome or the BCR/ABL fusion gene. None of the common
      cytogenetic abnormalities characteristic of myeloid disorders were detected. Two
      patients demonstrated clonal evolution during the course of the disease. All
      responded initially to therapy with hydroxyurea with control of leukocytosis and
      reduction in splenomegaly. Three patients eventually became refractory to
      hydroxyurea, manifesting progressive neutrophilia without blastic transformation.
      Aggressive chemotherapy to control progressive leukocytosis resulted in death due
      to cytopenias in two of these patients. The third patient received less intensive
      chemotherapy and died of progressive disease. One patient died after
      transformation of the disease into undifferentiated acute myeloid leukemia. Two
      patients remain alive with stable disease on hydroxyurea therapy, 12 and 54
      months after initial diagnosis. Chronic neutrophilic leukemia is a rare
      clinicopathologic entity that can be distinguished from chronic myelogenous
      leukemia, the recently described neutrophilic-chronic myelogenous leukemia, and
      myelodysplastic syndrome. The clinical course is heterogeneous, with a definite
      risk of death from either blastic transformation or progressive neutrophilic
      leukocytosis. Continued study and reporting of these cases must be encouraged.

PMID- 11243397
TI  - Second malignancy after treatment of childhood acute myeloid leukemia.
AB  - To investigate the cumulative incidence of second malignancy and the competing
      risk of death due to any other cause in patients who were treated for childhood
      acute myeloid leukemia (AML), we analyzed the outcomes in a cohort of 501
      patients who were treated at St Jude Children's Research Hospital between 1970
      and 1996. Five patients developed a second cancer (two carcinomas of the parotid
      gland, one non-Hodgkin's lymphoma, one supratentorial primitive neuroectodermal
      tumor, one acute lymphoblastic leukemia) as compared with 0.47 expected in the
      general population (standardized incidence ratio, 10.64; 95% confidence interval,
      3.28 to 22.34). A third neoplasm (meningioma) developed in one patient. At 15
      years after the diagnosis of AML, the estimated cumulative incidence of second
      malignancy was 1.34% +/- 0.61%, whereas the cumulative incidence of death due to
      any other cause was 72.96% +/- 2.14%. We concluded that although a more than 10
      fold increased risk of development of cancer was found in survivors of childhood
      AML as compared to the general population, the risk of this late complication is
      small when compared to the much larger risk of death because of the primary
      leukemia or the early complications of its treatment. Future studies should focus
      on improving treatments for primary AML while preventing second malignancies.

PMID- 11243398
TI  - Extramedullary infiltrates at diagnosis have no prognostic significance in
      children with acute myeloid leukaemia.
AB  - This retrospective study was designed to review the relative frequency and
      prognostic significance of extramedullary infiltrates in children with acute
      myeloid leukaemia (AML). The registration data and initial discharge summaries
      were reviewed for all children diagnosed with AML, and registered by the Dutch
      Childhood Leukaemia Study Group (DCLSG). Between 1972 and 1998, 477 children were
      diagnosed with AML. Of these patients, 120 (25.1%) had extramedullary leukaemia
      (EML) at diagnosis. Four categories of EML were found: skin, soft tissue or bone,
      gingival infiltration and central nervous system (CNS) involvement. Patients who
      presented with gingival infiltrates, were older than those without EML or those
      in the other EML subgroups, had a high initial WBC count and a high proportion of
      M4/M5 morphological variants. This type of presentation could indicate a special
      biological entity. Univariate analysis of prognostic factors in patients treated
      after 1985 with intensive protocols showed that initial WBC count and the
      presence of favourable cytogenetic findings were significant. The presence of EML
      at diagnosis had no significant effect on event-free survival. In a stepwise
      multiple regression analysis only favourable cytogenetic findings remained
      significant.

PMID- 11243399
TI  - Purified autologous grafting in childhood acute lymphoblastic leukemia in second
      remission: evidence for long-term clinical and molecular remissions.
AB  - Autologous transplantation is a treatment option for relapsed childhood acute
      lymphoblastic leukemia (ALL) in second complete remission (CR2) when a suitable
      donor is not available. In an attempt to prevent relapses originating from graft
      leukemic contamination, the experimental protocol of in vitro purification of
      leukapheretic products with monoclonal antibodies (MoAbs), previously reported
      for adults, was adopted in 11 of 12 consecutive patients (median age, 9 years)
      with B cell precursor ALL in CR2 after late relapse (median, 37; range, 31-51
      months after the onset) enrolled between July 1997 and July 1999 at a single
      pediatric center. At a median of 12 days after the mobilizing chemotherapy
      followed by G-CSF, a median of 13.9 (range, 5.9-18.7) x 10(6) CD34+ cells/kg were
      collected from each patient and a median of 7.5 (range, 4.1-12.6) x 10(6) CD34+
      cells/kg underwent the purification procedure. The first step of immunorosetting
      allowed a one-log reduction of the total cell count, by eliminating more than 90%
      of the CD11b+ cells; the second step, performed after incubation with anti-CD19
      MoAbs, allowed the depletion of 99% (range, 93-100) of the CD19+ cells, kept
      within the magnetic field of the immunodepletion column, with a median recovery
      of 73% (range, 55-87) of the collected CD34+ cells. Molecular analysis assessed
      the in vitro eradication of detectable leukemic cells. A median reinfusion of 5.2
      (range, 3.2-9.1) x 10(6) CD34+ cells/kg for each patient (median viability, 90%),
      after conditioning with the 'TBI-VP16-CY' regimen, allowed prompt engraftment and
      immunological reconstitution; no patients experienced severe transplant-related
      toxicity or major infections. One patient relapsed 7 months after
      transplantation, while 10 patients are alive in clinical and molecular remission,
      at a median follow-up of 29 months (range, 15-40) (2-year EFS, 89%, s.e. 9). In
      conclusion, the procedure proved to be reproducible for pediatric purified
      autografting, highly efficient concerning stem cell recovery and depletion of
      leukemia-lineage specific cells, and promising in terms of final outcome.

PMID- 11243400
TI  - Comparison of outcome in acute myelogenous leukemia patients with translocation
      (8;21) found by standard cytogenetic analysis and patients with AML1/ETO fusion
      transcript found only by PCR testing.
AB  - Patients with normal-karyotype acute myelogenous leukemia (NKAML) may have
      undetected genetic abnormalities that could affect prognosis. Screening for known
      AML-specific genetic abnormalities using the reverse transcription polymerase
      chain reaction (RT-PCR) may help in arriving at a more definitive prognosis. To
      test this hypothesis, 104 patients without translocation (8;21) and
      inversion(16), as shown by standard cytogenetic (SC) analysis, were screened for
      these two genetic abnormalities using RT-PCR. Western blot analysis for the
      AML1/ETO fusion protein and fluorescent in situ hybridization (FISH) analysis for
      t(8;21) were performed in patients for whom we had samples. The characteristics
      and outcome after high-dose cytarabine containing treatments in five patients
      with t(8;21) shown by RT-PCR alone were then compared to 21 patients with t(8;21)
      detected using SC analysis. Eight of the 104 patients had masked t(8;21) and none
      had masked inv(16), as shown by RT-PCR. Five of 54 patients with NKAML had a
      detectable AML1/ETO fusion RNA transcript. Western blot analysis showed the
      AML1/ETO fusion protein in four of the seven patients for whom we had samples
      among the eight with masked t(8;21) shown by RT-PCR. All patients with t(8;21)
      shown by RT-PCR had negative FISH results. Ninety percent (n=19) of the patients
      with t(8;21) shown by SC analysis and 40% (n= 2) of the patients with t(8;21)
      shown by RT-PCR alone achieved a complete remission (P value 0.03). These data
      suggest that the outcome of NKAML patients with t(8;21) shown by RT-PCR is not
      equivalent to patients with t(8;21) by SC studies.

PMID- 11243401
TI  - Proliferating status of peripheral blood progenitor cells from patients with
      BCR/ABL-positive chronic myelogenous leukemia.
AB  - To investigate the mechanisms behind the leukemic expansion of BCR/ABL-positive
      chronic myelogenous leukemia (CML), we examined the cell cycle status of
      hematopoietic progenitor cells from peripheral blood (PB) and bone marrow (BM) of
      37 patients with newly diagnosed BCR/ABL-positive CML. We found a high proportion
      of 12.51 +/- 1.19% of CD34+ peripheral blood progenitor cells (PBPC) in S/G2M
      phase. Comparison of PB and BM from 19 cases revealed similar proliferation rates
      (10.74 +/- 1.41% vs 15.97 +/- 1.95%). Furthermore, even primitive CD34+/CD38-
      PBPC displayed high proliferation rates (17.45 +/- 2.98%) in 10 cases examined.
      In contrast, PBPC from 11 patients with BCR/ABL-negative myeloproliferative
      disorders were almost noncycling (S/G2M 1.46 +/- 0.47%). When matched pairs of PB
      and BM from six patients with BCR/ABL-negative myeloproliferative disorders were
      examined, only 0.89 +/- 0.41% of the CD34+ PBPC, but 8.29 +/- 3.13% CD34+ cells
      from BM were in S/G2M phase. Consistently, as compared to 19 patients with newly
      diagnosed BCR/ABL-positive CML, a significantly lower PB/BM ratio of CD34+ cells
      in S/G2M phase was found in these six patients with BCR/ABL-negative
      myeloprolifrative disorders. Administration of the tyrosine kinase inhibitor
      STI571 to 13 patients with CML in chronic phase, accelerated phase, or blast
      crisis lead to an inhibition of PBPC proliferation within a few days.
      Interestingly, CD34+ hematopoietic progenitor cells from BM remained
      proliferating in five cases examined, indicating that CML PBPC are more easily
      inhibited by STI571 as compared to CD34+ CML hematopoietic progenitor cells from
      BM. These data suggest that BCR/ABL leads to an enhanced cell cycle activation of
      CD34+ cells, which seems to be, at least in part, independent of additional
      factors provided by the bone marrow microenvironment.

PMID- 11243402
TI  - Modulation of ara-CTP levels by fludarabine and hydroxyurea in leukemic cells.
AB  - The rate of ara-cytosine triphosphate (ara-CTP) accumulation and its retention
      has been correlated with 1-beta-D-arabinofuranosylcytosine (ara-C)-mediated
      toxicity and clinical outcome in childhood and adult leukemia. We tested to what
      extent preincubation with the ribonucleotide reductase inhibitors fludarabine (F
      ara-A) and hydroxyurea (HU) enhanced ara-CTP levels in two human myeloid (HL-60,
      CMK) and two lymphoblastic leukemia cell lines (MOLT-4, BLIN-1) and also in
      blasts from 28 children with acute leukemia (AML: 14, ALL: 14). Incubation
      experiments carried out with cell lines showed F-ara-A and HU to be equipotent in
      increasing ara-CTP levels. The highest increase was observed in HL-60 cells
      whereas preincubation had no modulatory effect in MOLT-4 cells. Accordingly,
      modulation of intracellular ara-CTP levels differed between the subtypes of
      childhood acute leukemia: whereas in T-ALL (five) preincubation with F-ara-A and
      HU had no effect on intracellular ara-C metabolism, increased ara-CTP levels were
      seen in some cases of pre-B-ALL (seven). In myelogenous blasts (12) clinically
      relevant enhancement of ara-C toxification was regularly obtained with both, F
      ara-A (1.9-fold) and HU (1.5-fold). In conclusion, our data suggest that
      combinations of ara-C and ribonucleotide reductase inhibitors are apt to increase
      ara-CTP levels depending on the individual cell type and its sensitivity towards
      ara-C modulators.

PMID- 11243403
TI  - 6-mercaptopurine dosage and pharmacokinetics influence the degree of bone marrow
      toxicity following high-dose methotrexate in children with acute lymphoblastic
      leukemia.
AB  - Through inhibition of purine de novo synthesis and enhancement of 6
      mercaptopurine (6MP) bioavailability high-dose methotrexate (HDM) may increase
      the incorporation into DNA of 6-thioguanine nucleotides (6TGN), the cytoxic
      metabolites of 6MP. Thus, coadministration of 6MP could increase myelotoxicity
      following HDM. Twenty-one children with standard risk (SR) and 25 with
      intermediate risk (IR) acute lymphoblastic leukemia (ALL) were studied. During
      consolidation therapy they received either three courses of HDM at 2 week
      intervals without concurrent oral 6MP (SR-ALL) or four courses of HDM given at 2
      week intervals with 25 mg/m2 of oral 6MP daily (IR-ALL). During the first year of
      maintenance with oral 6MP (75 mg/m2/day) and oral MTX (20 mg/m2/week) they all
      received five courses of HDM at 8 week intervals. In all cases, HDM consisted of
      5,000 mg of MTX/m2 given over 24 h with intraspinal MTX and leucovorin rescue.
      Erythrocyte levels of 6TGN (E-6TGN) and methotrexate (E-MTX) were, on average,
      measured every second week during maintenance therapy. When SR consolidation
      (6MP: 0 mg), IR consolidation (6MP: 25 mg/m2), and SR/IR maintenance therapy
      (6MP: 75 mg/m2) were compared, white cell and absolute neutrophil count (ANC)
      nadir, lymphocyte count nadir, thrombocyte count nadir, and hemoglobin nadir
      after HDM decreased significantly with increasing doses of oral 6MP. Three
      percent of the HDM courses given without oral 6MP (SR consolidation) were
      followed by an ANC nadir <0.5 x 10(9)/l compared to 50% of the HDM courses given
      during SR/IR maintenance therapy. Similarly, only 13% of the HDM courses given as
      SR-ALL consolidation induced a thrombocyte count nadir <100 x 10(9)/l compared to
      58% of the HDM courses given during maintenance therapy. The best-fit model to
      predict the ANC nadir following HDM during maintenance therapy included the dose
      of 6MP prior to HDM (beta = -0.017, P= 0.001), the average ANC level during
      maintenance therapy (beta = 0.82, P = 0.004), and E-6TGN (beta = -0.0029, P=
      0.02). The best-fit model to predict the thrombocyte nadir following HDM during
      maintenance therapy included only mPLATE (beta = 0.0057, P = 0.046). In
      conclusion, the study indicates that reductions of the dose of concurrently given
      oral 6MP could be one way of reducing the risk of significant myelotoxicity
      following HDM during maintenance therapy of childhood ALL.

PMID- 11243404
TI  - Cyclosporin increases cellular idarubicin and idarubicinol concentrations in
      relapsed or refractory AML mainly due to reduced systemic clearance.
AB  - The feasibility of adding both the multidrug resistance modulator cyclosporin
      (CsA) and granulocyte colony-stimulating factor (G-CSF) to a standard salvage
      regimen of idarubicin (IDA) and cytarabine was evaluated in patients with
      resistant or relapsed acute myeloid leukemia and myelodysplastic syndrome. Three
      patients received IDA 12 mg/m2/day, the next four patients 9 mg/m2/day. The dose
      of CsA was 16 mg/kg/day. Six patients showed Pgp expression and none MRP1
      expression. Grade III or IV toxicity (CTC-NCIC criteria) was registered in six
      patients for gastrointestinal, two patients for cardiovascular and one patient
      for neurological complications. Three patients died in hypoplasia and three
      patients showed leukemic regrowth. Three control patients were treated with IDA
      12 mg/m2/day and cytarabine, but no CsA and G-CSF. The plasma IDA and
      idarubicinol (ida-ol) area under the curve's of patients treated with IDA 12
      mg/m2 plus CsA were higher (P< 0.05) than in controls. Cellular IDA
      concentrations were almost similar, but cellular ida-ol concentrations were
      significantly higher (P < 0.05) in the presence of CsA than in controls. We
      conclude that the toxicity either with IDA 12 or 9 mg/m2/day was too high. The
      modulating effect of CsA was mainly based on changes in plasma kinetics of IDA
      and ida-ol, although ida-ol cellular clearance was delayed in the presence of
      CsA.

PMID- 11243405
TI  - Fusion of MOZ and p300 histone acetyltransferases in acute monocytic leukemia
      with a t(8;22)(p11;q13) chromosome translocation.
AB  - Histone acetyltransferase p300 functions as a transcriptional co-activator which
      interacts with a number of transcription factors. Monocytic leukemia zinc finger
      protein (MOZ) has histone acetyltransferase activity. We report the fusion of the
      MOZ gene to the p300 gene in acute myeloid leukemia with translocation
      t(8;22)(p11;q13). FISH and Southern blot analyses showed the rearrangement of the
      MOZ and p300 genes. We determined the genomic structure of the p300 and the MOZ
      genes and the breakpoints of the translocation. Analysis of fusion transcripts
      indicated that the zinc finger and acetyltransferase domains of MOZ are fused to
      a largely intact p300. These results suggest that MOZ-p300, which has two
      acetyltransferase domains, could be involved in leukemogenesis through aberrant
      regulation of histone acetylation.

PMID- 11243406
TI  - Detection of E2A translocations in leukemias via fluorescence in situ
      hybridization.
AB  - Three rearrangements in ALL disrupt E2A and create E2A fusion proteins: the
      t(1;19)(q23;p13) and E2A-PBX1, t(17;19)(q22;p13) and E2A-HLF and a cryptic
      inv(19)(p13;q13) and E2A-FB1. While E2A is fused to PBX1 in most ALLs with a
      t(1;19), 5-10% of cases have translocations that appear identical, but do not
      affect E2A or PBX1. Because more intensive therapy improves the outcome of
      patients with E2A-PBX1positive (1;19) translocations, it is critical to identify
      this subset of patients so that appropriate therapy can be administered. In
      addition, there are balanced and unbalanced variants of the t(1;19) and
      controversy exists regarding the clinical significance of this distinction. We
      have developed a two-color fluorescence in situ hybridization assay that
      accurately detects E2A translocations in metaphase and interphase cells,
      distinguishes between balanced and unbalanced variants and identifies patients
      with a t(1;19) who lack E2A-PBX1 fusion. We found that clonal microheterogeneity
      is common in patients with E2A translocations and most patients have mixtures of
      cells with balanced and unbalanced translocations, suggesting that this
      distinction represents two ends of a continuum rather than distinct biological
      entities. These reagents should have widespread clinical utility and be useful
      for translational and basic research studies involving E2A translocations and
      this region of chromosome 19p13.

PMID- 11243407
TI  - The role of NF-kappaB in the regulation of the expression of wilms tumor
      suppressor gene WT1.
AB  - The Wilms tumor suppressor gene, WT1, plays an important role in genitourinary
      development and the etiology of Wilms tumor. WT1 has a spatially and temporally
      defined expression in the developing genitourinary system and in specific cells
      of the hematopoietic system, but the regulatory pathways that control WT1
      expression are not well understood. Recently, members of the NF-kappaB family of
      transcription factors have been proposed as potent activators of the murine WT1
      promoter through binding to a NF-kappaB site. Because the human WT1 promoter
      contains a conserved NF-kappaB site, we investigated whether NF-kappaB also
      regulates the expression of the human WT1 gene. We activated NF-kappaB through
      cytokine stimulation or inhibited NF-kappaB through expression of a NF-kappaB
      "super repressor" in WT1 expressing Wilms tumor, renal carcinoma, and
      erythroleukemia cultures and examined the level of endogenous WT1 gene
      expression. Although a transfected NF-kappaB reporter construct was responsive to
      these manipulations, we found that altering NF-kappaB activity had no effect on
      endogenous WT1 expression in the cell types used in our study. We conclude that
      despite the presence of conserved NF-kappaB elements in the murine and human WT1
      promoters, NF-kappaB is not required to regulate the expression of the WT1 gene
      in its natural context.

PMID- 11243408
TI  - Human parainfluenza virus type 3 upregulates ICAM-1 (CD54) expression in a
      cytokine-independent manner.
AB  - Human parainfluenza virus type 3 (HPIV3) causes bronchiolitis, pneumonia, and
      croup in newborns and infants. Several studies have implicated intercellular
      adhesion molecule-1 (ICAM-1) in inflammation during infection by viruses. In this
      study, we investigated the potential for HPIV3 to induce ICAM-1 in HT1080 cells.
      FACS analysis showed that HPIV3 strongly induced ICAM-1 expression in these
      cells. The ICAM-1 induction was significantly reduced when the virions were UV
      inactivated prior to infection, indicating that ICAM-1 induction was mostly viral
      replication dependent. Culture supernatant of HPIV3-infected cells induced ICAM-1
      at an extremely low level, indicating that virus-induced cytokines played only a
      minor role in the induction process. Consistent with this, potent inducers of
      ICAM-1 such as IFN-gamma, TGF-beta, and TNF-alpha were absent in the culture
      supernatant, but a significant amount of IFN type 1 was present. By using U2A
      cells, which are defective in IFN type I signaling, we confirmed that ICAM-1
      induction by HPIV3 occurred in a JAK/STAT signaling-independent manner. These
      data strongly indicate that HPIV3 induces ICAM-1 directly by viral antigens in a
      cytokine-independent manner; this induction may play a role in the inflammation
      during HPIV3 infection.

PMID- 11243409
TI  - The Drosophila TATA binding protein contains a strong but masked activation
      domain.
AB  - TATA binding protein (TBP) is a critical transcription factor involved in
      transcription by all three RNA polymerases (RNAPs). Studies using in vitro
      systems and yeast have shown that the C-terminal core domain (CTD) of TBP is
      necessary and sufficient for many TBP functions, but the significance of the N
      terminal domain (NTD) of TBP is still obscure. Here, using transient expression
      assays in Drosophila Schneider cells, we show that the NTD of Drosophila TBP
      (dTBP) strongly activates transcription when fused to the GAL4 DNA binding domain
      (DBD). Strikingly, the activity of the NTD is completely repressed in the context
      of full-length dTBP. In contrast to the much weaker activation obtained by either
      full-length dTBP or the dTBP CTD fused to the GAL4 DBD, activation by the NTD is
      dependent on the presence of GAL4 binding sites and is susceptible to the effects
      of a dominant negative TFIIB mutant, TFIIB deltaC202, a property observed
      previously with certain authentic activation domains. Activation by the NTD, but
      not full-length dTBP or the CTD, seems to be mediated by the action of a strong
      activation domain, likely a glutamine-rich region. In conclusion, the dTBP NTD
      can behave as a very strong activator that is masked in the full-length protein,
      suggesting possible roles for the dTBP NTD in RNAP II-mediated transcription.

PMID- 11243410
TI  - Inhibition of translation of mRNAs containing gamma-monomethylphosphate cap
      structure in frog oocytes and in mammalian cells.
AB  - The gamma-monomethylphosphate cap structure is found in several eukaryotic small
      RNAs including nuclear U6, U6atac, 7SK, plant nucleolar U3, and rodent
      cytoplasmic B2 RNAs. In the case of human U6 snRNA, the 5' end sequence
      corresponding to nucleotides 1-25 serves as the capping signal and directs the
      formation of methylphosphate cap structure. In this study, we show that the U6
      RNA capping signal, when introduced at the 5' end of RNAs, can efficiently direct
      the methylphosphate cap formation in RNAs of up to 2.7 kb long, as well as in
      different mRNAs. These data show that the methylphosphate capping signal
      functions in mRNAs having different primary sequences and different lengths.
      Presence of the methylphosphate cap structure on the 5' end of a luciferase mRNA
      with EMCV 5' noncoding region, which is translated in an IRES-dependent pathway,
      resulted in a 6- to 100-fold inhibition of translation compared to the same mRNA
      with a 5' triphosphate when microinjected into frog oocytes or expressed in mouse
      cells in tissue culture. Thus, conversion of the pppG structure to a methyl-pppG
      structure on the 5' end of an mRNA, which is translated in an IRES-dependent
      pathway, results in severe inhibition of translation. These data show that the 5'
      end motif of mRNAs plays an important role even in the IRES-mediated mRNA
      translation.

PMID- 11243411
TI  - An antiprion effect of the anticytoskeletal drug latrunculin A in yeast.
AB  - Prions are infectious aggregation-prone isoforms of the normal proteins,
      supposedly able to seed aggregation of the normal cellular counterparts. In
      vitro, prion proteins form amyloid fibers, resembling cytoskeletal structures.
      Yeast prion [PSI], which is a cytoplasmically inherited aggregated isoform of the
      translation termination factor Sup35p (eRF3), serves as a useful model for
      studying mechanisms of prion diseases and other amyloidoses. The previously
      described interaction between Sup35p and cytoskeletal assembly protein Sla1p
      points to the possible relationships between prions and cytoskeletal networks.
      Although the Sup35PSI+ aggregates do not colocalize with actin patches, we have
      shown that yeast cells are efficiently cured of the [PSI] prion by prolonged
      incubation with latrunculin A, a drug disrupting the actin cytoskeleton. On the
      other hand, treatments with sodium azide or cycloheximide, agents blocking yeast
      protein synthesis and cell proliferation but not disrupting the cytoskeleton, do
      not cause a significant loss of [PSI]. Moreover, simultaneous treatment with
      sodium azide or cycloheximide blocks [PSI] curing by latrunculin A, indicating
      that prion loss in the presence of latrunculin A requires a continuation of
      protein synthesis during cytoskeleton disruption. The sodium azide treatment also
      decreases the toxic effect of latrunculin A. Latrunculin A influences neither the
      levels of total cellular Sup35p nor the levels of chaperone proteins, such as
      Hsp104 and Hsp70, which were previously shown to affect [PSI]. This makes an
      indirect effect of latrunculin A on [PSI] via induction of Hsps unlikely.
      Fluorescence microscopy detects changes in the structure and/or localization of
      the Sup35PSI+ aggregates in latrunculin A-treated cells. We conclude that the
      stable maintenance of the [PSI] prion aggregates in the protein-synthesizing
      yeast cells partly depends on an intact actin cytoskeleton, suggesting that
      anticytoskeletal treatments could be used to counteract some aggregation-related
      disorders.

PMID- 11243412
TI  - The 5' repeat elements of the mouse Xist gene inhibit the transcription of X
      linked genes.
AB  - X chromosome inactivation in mammals requires the Xist gene, which is exclusively
      expressed from the inactive X chromosome (Xi). The large heterogeneous Xist
      nuclear RNA colocalizes with Xi, most likely through nuclear protein
      interactions. The 5' region of the Xist RNA contains a series of well-conserved
      tandem repeats known to bind heteronuclear proteins in vitro and to enhance human
      XIST transcription. We show in an in vitro system that the conserved repeat
      element located in the 5' region of the mouse Xist gene (Xcr) represses three X
      linked genes but has no effect on the autosomal genes Aprt, Ins, and the viral
      SV40 gene. The repression effect is not mediated by the conserved core sequence
      (Ccs) of Xcr, but requires the presence of the complete Xcr. This Xcr effect on X
      linked genes suggests that Xcr transcript recognizes the genes to be silenced and
      is involved in the spreading of X inactivation.

PMID- 11243413
TI  - Effects of ouabain on the growth and DNA synthesis of PC12 cells.
AB  - We investigated the effects of ouabain and serum from salt-loaded Dahl salt
      sensitive (S) rats, which contain abundant ouabain-like compounds, on the growth
      and DNA synthesis of rat pheochromocytoma PC12 cells. Ouabain decreased the
      growth of PC12 cells, as evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide assay, in a concentration-dependent fashion. A
      moderate concentration (10(-7) M) of ouabain increased DNA synthesis, as measured
      by 5-bromo-2'-deoxyuridine incorporation, and induced transcription of the proto
      oncogenes c-myc and c-fos. Serum from salt-loaded Dahl S rats also enhanced DNA
      synthesis, but serum from Dahl salt-resistant rats did not. Thus ouabain-like
      compounds may modify the growth or differentiation of neural tissues. This effect
      may contribute to the development of salt-induced hypertension in Dahl S rats.

PMID- 11243415
TI  - Relative importance of rostral ventrolateral medulla in sympathoinhibitory action
      of rilmenidine in conscious and anesthetized rabbits.
AB  - The pressor region of the rostral ventrolateral medulla (RVLM) is a critical site
      in the sympathoinhibitory action of imidazoline receptor agonists as shown by
      studies in anesthetized animals. The aim of this study was to compare the
      importance of the RVLM in mediating the inhibitory action of rilmenidine on renal
      sympathetic nerve activity (RSNA) and arterial pressure in urethane-anesthetized
      rabbits (n = 11) and in conscious, chronically instrumented rabbits (n = 6).
      Bilateral microinjection of rilmenidine (4 nmol in 100 nl) into the RVLM caused a
      greater decrease in resting arterial pressure in anesthetized animals (-19 mm Hg)
      than in conscious animals (-8 mm Hg). By contrast, the decrease in resting RSNA
      evoked by rilmenidine was similar in conscious (-27%) and anesthetized (-36%)
      rabbits. Furthermore, rilmenidine microinjection into the RVLM was equally
      effective in inhibiting the RSNA baroreflex in both groups of animals. The upper
      plateau of the RSNA baroreflex decreased by 37% and 42%, and gain decreased by
      41% and 44% after rilmenidine treatments in conscious and anesthetized rabbits,
      respectively. We conclude that the RVLM plays an equally important role in the
      inhibitory action of rilmenidine on RSNA in conscious and anesthetized rabbits
      either at rest or during baroreflex responses. A relatively moderate effect of
      rilmenidine on arterial pressure in conscious, chronically instrumented rabbits
      may relate to a lower level of sympathetic drive compared with anesthetized
      animals.

PMID- 11243414
TI  - Effects of inhaled prostacyclin analogue on chronic hypoxic pulmonary
      hypertension.
AB  - Inhaled PGI2 has been reported to elicit pulmonary vasodilation, but whether it
      is also effective in treating chronic hypoxic pulmonary hypertension is still
      uncertain. We designed this study to address the in vivo effectiveness of inhaled
      Beraprost, a stable PGI2 analogue, on pulmonary vascular tone during hypoxic
      exposure in normoxic (N) and chronically hypoxic (CH) rats. Pulmonary
      vasodilation was observed by low-dose inhaled Beraprost in N rats, but not in CH
      rats. It was not until higher doses of Beraprost were given that pulmonary
      vasodilation was obtained in CH rats. When the agent was continuously
      administered by an intravascular route at the inhaled dose, it elicited no
      vasodilation in N rats. On the contrary, it elicited profound vasodilation in CH
      rats, although a concomitant systemic hypotension was observed. The PGI2 receptor
      mRNA expression was unchanged in the lungs of CH rats compared with that of N
      rats. We conclude that low doses of aerosolized Beraprost may reduce pulmonary
      vascular tone in rats without preexisting lung diseases. In contrast, when
      hypoxic pulmonary hypertension is present, the threshold of Beraprost inhalation
      was elevated to provoke pulmonary vasodilation.

PMID- 11243416
TI  - Resveratrol, a polyphenol found in wine, reduces ischemia reperfusion injury in
      rat kidneys.
AB  - Reactive oxygen species have been implicated in the pathophysiology of renal
      ischemia reperfusion injury. Antioxidants including polyphenolics have been found
      to protect renal cells from the cellular injury induced by ischemia and
      reperfusion. Resveratrol, a stilbene polyphenol found in grapes and red wine, has
      recently been found to protect isolated rat heart from ischemia reperfusion
      injury. This study was sought to determine if resveratrol could also protect
      renal cells from ischemic injury. Male Wistar rats were treated with control,
      resveratrol (0.23 microg/kg), vehicle used to solubilize resveratrol, and
      resveratrol plus L-NAME (15 mg/kg body wt), a nitric oxide blocker. Our results
      demonstrated that resveratrol administration reduced the mortality of ischemic
      rats from 50% to 10% and renal damage was reduced as indicated by histologic
      examination and serum creatinine level. The short-term administration of
      resveratrol also inhibited renal lipid peroxidation induced by ischemia and
      reperfusion both in cortex and in medulla. Electron paramagnetic resonance
      detected an increased formation of nitric oxide in the resveratrol-treated kidney
      that was reduced to the baseline value after treating the rats with L-NAME in
      addition to resveratrol. The results suggest that resveratrol reduced the renal
      ischemia reperfusion injury through a nitric oxide-dependent mechanism.

PMID- 11243417
TI  - KB-R7943, a selective Na+/Ca2+ exchange inhibitor, protects against ischemic
      acute renal failure in mice by inhibiting renal endothelin-1 overproduction.
AB  - We investigated whether the preischemic or postischemic treatment with KB-R7943,
      a novel and selective Na+/Ca2+ exchange inhibitor, has renal protective effects
      in mice with ischemic acute renal failure (ARF). Ischemic ARF was induced by
      clamping the left renal pedicle for 45 min followed by reperfusion, 2 weeks after
      contralateral nephrectomy. Renal function was markedly diminished 24 h after
      reperfusion. Preischemic treatment with KB-R7943 attenuated the ARF-induced renal
      dysfunction. The ischemia/reperfusion-induced renal dysfunction was also overcome
      by postischemic treatment with KB-R7943. Histopathologic examination of the
      kidneys of ARF mice revealed severe renal damage such as tubular necrosis,
      proteinaceous casts in tubuli, and medullary congestion. Histologically evident
      damage and Ca2+ deposition in necrotic tubular epithelium were improved by
      preischemic treatment with KB-R7943. In addition, preischemic treatment with KB
      R7943 significantly suppressed the increment of endothelin-1 (ET-1) content in
      the kidney at 2, 6, and 24 h after reperfusion. These findings suggest that Ca2+
      overload via the reverse mode of Na+/Ca2+ exchange, followed by renal ET-1
      overproduction, plays an important role in the pathogenesis of the
      ischemia/reperfusion-induced ARF. KB-R7943 may prove to be an effective
      therapeutic agent for cases of ischemic ARF in humans.

PMID- 11243418
TI  - Hemodynamic and electrocardiographic effects of almotriptan in healthy
      volunteers.
AB  - We studied the possible cardiovascular effects of single oral doses of 12.5, 25,
      and 50 mg of almotriptan, a new triptan for treatment of migraine, in a
      randomized, double-blind, four-way crossover, placebo-controlled study in 24
      healthy volunteers aged 18 to 35 years. Doses were given at 1-week intervals.
      Cardiovascular effects were assessed by frequent recording of blood pressure and
      heart rate, 12-lead electrocardiogram (ECG) (recorded at 25 mm/s paper speed and
      1 cm/mV and at 50 mm/s and 2 cm/mV), and continuous ECG monitoring for 12 h after
      each dose. ECG variables, PR, QRS, QT interval, and QT dispersion, were measured.
      QT intervals were adjusted for heart rate using Bazett's formula. None of the
      doses of almotriptan differed significantly from placebo with respect to PR, QRS,
      or QTc intervals, QTc dispersion, heart rate, or continuous ECG monitoring.
      Almotriptan 12.5 mg did not differ significantly from placebo with respect to
      systolic or diastolic blood pressure, but almotriptan 25 and 50 mg raised
      systolic blood pressure by a mean of 2.78 and 4.17 mm Hg, and diastolic blood
      pressure by 3.77 and 6.11 mm Hg, respectively, during 0 to 4 h after dosing. Thus
      none of the doses of almotriptan affected the ECG, and the 12.5-mg dose (the
      expected therapeutic dose) had no hemodynamic effects. Almotriptan in doses of 25
      and 50 mg caused a small, dose-related increase in systolic and diastolic blood
      pressure, as seen with other triptans.

PMID- 11243419
TI  - Increased sensitivity of vascular smooth muscle to nitric oxide in dilated
      cardiomyopathy of Syrian hamsters (Bio TO-2 strain).
AB  - We assessed the evolution with time of the responsiveness of three vascular beds
      in dilated cardiomyopathic hamsters of the Bio TO-2 strain. Eight cardiomyopathic
      hamsters and 8 control hamsters were investigated at 180 and 300 days of age.
      Thoracic aorta and mesenteric and renal artery rings were studied in isolated
      organ baths. Cumulative concentration-response relations to phenylephrine,
      acetylcholine, sodium nitroprusside, and angiotensin II were established for each
      ring. Maximum effect (Emax) and concentration inducing 50% of Emax (EC50) were
      determined from each concentration-response curve and pD2 was calculated as 
      log(EC50). Compared with control hamsters, in cardiomyopathic hamsters, Emax of
      phenylephrine was not modified in aorta, whereas it was significantly lower in
      mesenteric (-6% and -33% at 180 and 300 days, respectively) and renal (-17% and 
      24%) arteries. Emax of acetylcholine was significantly higher in aorta (+57% and
      +30%), mesenteric (+42% and +34%), and renal (+168% and +70%) arteries. Emax of
      sodium nitroprusside was significantly higher in aorta (+26% and +16%) and tended
      to be higher in mesenteric (+25% and +23%) and renal (+27% and +10%) arteries.
      Emax of angiotensin II was not modified in aorta and tended to be lower in
      mesenteric artery at 300 days. The pD2 of phenylephrine was significantly
      increased in aorta and the pD2 of sodium nitroprusside was significantly
      increased in aorta and renal artery. In conclusion, in dilated cardiomyopathic
      hamsters, endothelium-dependent and -independent vasodilations are enhanced
      early, demonstrating increased sensitivity of vascular smooth muscle to nitric
      oxide. This abnormality may be involved in the decreased responsiveness to
      phenylephrine and angiotensin II.

PMID- 11243420
TI  - Modulation of renal oxygen consumption by nitric oxide is impaired after
      development of congestive heart failure in dogs.
AB  - We investigated the role of nitric oxide (NO) in the modulation of renal O2
      consumption in dogs with pacing-induced congestive heart failure (CHF). O2
      consumption in the renal cortex (C) and medulla (M) of normal dogs and dogs with
      CHF was measured under control conditions and in the presence of increasing
      concentrations of three stimulators of NO production, bradykinin, ramiprilat, and
      amlodipine, or the NO donor S-nitroso-N-acetylpenicillamine (SNAP). Baseline O2
      consumption (nmol O2/min per gram) was similar in the CHF group (C: 637+/-65; M:
      618+/-83) and the control group (C: 601+/-58, M: 534+/-55). In normal dogs,
      bradykinin (10(-4) M), ramiprilat (10(-4) M), amlodipine (10(-5) M) and SNAP (10(
      4) M) all significantly reduced O2 consumption in the cortex (-31.5+/-3.5%, -33+/
      2.5%, -28.4+/-4.9%, -49.3+/-3.1%) and medulla (-26.9+/-2.2%, -31.4+/-2.2%, 
      23.1+/-1.3%, -48.3+/-4%), respectively. The responses to bradykinin, ramiprilat
      and amlodipine were significantly attenuated in dogs with CHF (C: -22.2+/-1.8%, 
      20.1+/-2.6%, -14.2+/-2.5%; M: -20.8+/-1.7%, -17.8+/-1.9%, -15.6+/-2.6%,
      respectively; p < 0.05). The responses in dogs with CHF were not altered by NO
      synthase blockade with L-NAME (10(-4) M). In contrast, in normal kidneys
      treatment with L-NAME significantly attenuated the response to all three stimuli
      of NO production. Responses to SNAP were not affected either by CHF or L-NAME.
      These data indicate that the role of NO production in the modulation of tissue O2
      consumption in the kidney is impaired after the development of pacing-induced
      heart failure in dogs.

PMID- 11243421
TI  - Low nitric oxide values associated with low levels of zinc and high levels of
      cardiac necrosis markers detected in the plasma of rabbits treated with L-NAME.
AB  - Nitric oxide plays a key role as a vasodilating agent and its deficiency is
      associated with ischemic heart diseases. The aim of this study was to induce
      biochemical alterations associated with ischemic heart lesions by blocking nitric
      oxide synthase. L-NAME, a nitric oxide synthase inhibitor, was administered to
      rabbits and its effects on blood pressure, plasma levels of nitric oxide, zinc
      and cardiac necrosis markers, heart histology, and electrocardiographic profile
      were examined. L-NAME administration reduced the nitric oxide levels and
      consequently increased the diastolic blood pressure. It also caused small areas
      of myocardial coagulative necrosis, whose dispersed nature made it undetectable
      by electrocardiograph, and decreased the plasma levels of zinc, which is involved
      in the enzymatic activities that remove the peroxides damaging the myocardium.
      This model is proposed for the development of drugs affecting nitric oxide levels
      with the aim of controlling coronary ischemia.

PMID- 11243422
TI  - Restoration of normal ventricular electrophysiology in renovascular hypertensive
      rabbits after treatment with losartan.
AB  - Left ventricular hypertrophy (LVH) is associated with abnormal ventricular
      electrophysiology. We have shown complete regression of LVH and normalization of
      ventricular electrophysiology in renovascular hypertensive rabbits treated with
      captopril. To determine if angiotensin II type 1 receptor (AT1) blockade produces
      the same benefit, we treated hypertensive rabbits with losartan for 3 months. LVH
      was evaluated by heart-to-body weight ratio (HW/BW). Vulnerability to ventricular
      arrhythmia was assessed by ventricular fibrillation threshold (VFT) and
      dispersion of effective refractory period (ERP). The electrical properties of
      single left ventricular myocytes were characterized by action potential duration
      at 90% repolarization (APD90) and inward rectifier K+ current (I(K1)) density.
      Hypertensive rabbits treated with vehicle (LVH/Vehicle) had higher mean arterial
      pressure (MAP, 81+/-2 vs. 60+/-2 mm Hg) and HW/BW (2.71+/-0.07 vs. 1.97+/-0.04
      g/kg), lower VFT (20+/-1 vs. 39+/-2 mA), larger dispersion of ERP (34+/-3 vs.
      14+/-3 ms), longer APD90 (187+/-6 vs. 162+/-6 ms) and lower I(K1) density
      compared with control rabbits. Hypertensive rabbits treated with losartan
      (LVH/Losartan) had HW/BW (2.36+/-0.06 g/kg) between those of LVH/Vehicle and
      control rabbits, whereas MAP (65+/-2 mm Hg), VFT (34+/-2 mA), dispersion of ERP
      (19+/-1 ms), APD90 (160+/-6 ms), and I(K1) density were significantly different
      from LVH/Vehicle but similar to control. We conclude that AT1 blockade in
      renovascular hypertensive rabbits normalizes ventricular electrophysiology.

PMID- 11243423
TI  - Positive and negative contractile effects of somatostatin-14 on rat ventricular
      cardiomyocytes.
AB  - Somatostatin-14 elicits negative inotropic and chronotropic actions in atrial
      myocardium. Less is known about the effects of somatostatin-14 in ventricular
      myocardium. The direct contractile effects of somatostatin-14 were assessed using
      ventricular cardiomyocytes isolated from the hearts of adult rats. Cells were
      stimulated at 0.5 Hz with CaCl2 (2 mM) under basal conditions and in the presence
      of the beta-adrenoceptor agonist, isoprenaline (1 nM), or the selective inhibitor
      of the transient outward current (Ito), 4-aminopyridine (500 microM).
      Somatostatin-14 did not alter basal contractile response but it did inhibit (IC50
      = 13 nM) the response to isoprenaline (1 nM). In the presence of 4-aminopyridine
      (500 microM), somatostatin-14 stimulated a positive contractile response (EC50 =
      118 fM) that was attenuated markedly by diltiazem (100 nM). These data indicate
      that somatostatin-14 exerts dual effects directly in rat ventricular
      cardiomyocytes: (1) a negative contractile effect, observed in the presence of
      isoprenaline (1 nM), coupled to activation of Ito; and (2) a previously
      unreported and very potent positive contractile effect, unmasked by 4
      aminopyridine (500 microM), coupled to the influx of calcium ions via L-type
      calcium channels. The greater potency of somatostatin-14 for producing the
      positive contractile effect indicates that the peptide may exert a predominantly
      stimulatory influence on the resting contractility of ventricular myocardium in
      vivo, whereas the negative contractile effect, observed at much higher
      concentrations, could indicate that localized elevations in the concentration of
      the peptide may serve as a negative regulatory influence to limit the detrimental
      effects of excessive stimulation of cardiomyocyte contractility.

PMID- 11243424
TI  - Effect of vitamin C on the availability of tetrahydrobiopterin in human
      endothelial cells.
AB  - Vitamin C has long been known for its beneficial vascular effects, but its
      mechanism of action remains unclear. Recent reports suggest that vitamin C may
      prevent endothelial dysfunction by scavenging free radicals and increasing the
      bioavailability of nitric oxide. To investigate this area further, we studied the
      effect of vitamin C (10(-4) M) and Mn(III) tetrakis (4-benzoic acid) porphyrin
      chloride (MnTBAP; 10(-5) M), a scavenger of superoxide, hydrogen peroxide, and
      peroxynitrite, on endothelial nitric oxide synthase (eNOS) enzymatic activity in
      cultured human umbilical vein endothelial cells. L-Citrulline formation (a
      measure of eNOS enzymatic activity) was significantly increased in cells treated
      for 24 h with vitamin C. No effect was observed after MnTBAP treatment. Chronic
      administration of vitamin C also had no effect on eNOS protein expression.
      Treatment with vitamin C for 24 h significantly increased levels of the eNOS co
      factor tetrahydrobiopterin (BH4), whereas MnTBAP did not affect its levels.
      Sepiapterin (10(-4) M), a precursor of BH4, significantly increased eNOS
      activity, whereas addition of vitamin C to cells treated with sepiapterin did not
      cause any further increase in eNOS activity. Our results suggest that the
      beneficial effect of vitamin C on endothelial function is best explained by
      increased intracellular BH4 content and subsequent enhancement of eNOS activity.
      This effect appears to be independent of the ability of vitamin C to scavenge
      superoxide anions.

PMID- 11243426
TI  - Review of the diagnosis and management of acquired nasolacrimal duct obstruction.
AB  - BACKGROUND: Acquired nasolacrimal duct obstruction is a common cause of epiphora.
      The absolute or partial blockage of the nasolacrimal duct occurs most frequently
      in middle-aged and elderly women. In addition to the troublesome symptom of
      epiphora, acquired nasolacrimal duct obstruction is predominantly the underlying
      cause of both acute and chronic dacryocystitis. METHODS: The primary eye care
      provider plays an essential role in the diagnosis and management of the patient
      with epiphora. The potentially serious ramifications of acquired nasolacrimal
      duct obstruction demand a thorough understanding of the clinical presentation of
      this disorder. In addition, it is essential the optometrist be well-acquainted
      with the surgical treatments often necessary for optimal management. CONCLUSION:
      Whether treatment is provided or an appropriate referral is made, the optometrist
      is instrumental in providing care for the patient who experiences an acquired
      nasolacrimal duct obstruction.

PMID- 11243425
TI  - Acute pressor actions of ouabain do not enhance the actions of phenylephrine or
      norepinephrine in anesthetized rats.
AB  - The inhibition of high-affinity isoforms of the Na+,K+-ATPase by nanomolar levels
      of ouabain has been proposed to enhance the actions of vasoconstrictor agents
      that act via a Ca+2-dependent mechanism. The present study tested this hypothesis
      by evaluating the effects of ouabain (6 and 18 microg/kg, i.v.) on the
      vasopressor actions of phenylephrine and norepinephrine in anesthetized, reflex
      blocked rats. In separate groups of animals, dose-response curves for increases
      in diastolic pressure produced by phenylephrine were generated after the
      administration of saline (control), ouabain (18 microg/kg), L-omega-N-nitro
      arginine methyl ester (L-NAME, 3 micromol/kg) and angiotensin II (15 ng/kg per
      min). Treatment with ouabain (18 microg/kg) produced an increase in diastolic
      pressure of 19+/-3 mm Hg but did not significantly alter the potency or maximal
      response produced by phenylephrine. In contrast, treatment with angiotensin II
      and L-NAME, agents known to enhance the actions of alpha-adrenoceptor agonists,
      increased the potency of phenylephrine. In animals in which the pressor actions
      of norepinephrine were evaluated before and after the administration of ouabain
      (6 microg/kg), ouabain did not alter the pressor response to norepinephrine.
      Blockade of alpha-adrenoceptors with phentolamine was found to attenuate as well
      as partially reverse the increase in diastolic pressure produced by ouabain.
      These observations suggest that ouabain produces a pressor response by actions on
      sympathetic nerve endings as well as on vascular smooth muscle and that these
      actions do not alter the sensitivity to phenylephrine or norepinephrine.

PMID- 11243427
TI  - Ectropion secondary to bolus injection of 5-fluorouracil.
AB  - BACKGROUND: 5-fluorouracil (5-FU) targets rapidly dividing cancer cell
      populations. In turn, it may cause inflammation in such rapidly dividing tissues
      as the corneal epithelium, conjunctiva, and tear duct. Inflammation may be
      exacerbated by pre-existing dermatologic conditions. This case report describes a
      rare combination of facial dermatologic toxicity and ectropion. CASE REPORT: A 76
      year-old man came to us in October 1998 with symptoms of foreign body sensation,
      epiphora, and difficulty removing his contact lenses. His medical history was
      significant for 5-FU bolus injections for intestinal cancer since May 1998.
      Examination revealed facial erythema and eczema, ectropion, blepharitis,
      chemosis, lid teleangectasia, and contact lens-related corneal edema.
      Differential diagnoses included ocular rosacea with cicatrizing conjunctivitis
      and 5-FU-induced ectropion. He was treated and monitored over the subsequent
      several months. As of December 1998, only mild ectropion persisted. DISCUSSION:
      Patients with 5-FU-induced ectropion experience tender, red, scaled lids, making
      contact lens wear difficult. Therefore, contact lens wear should be discontinued
      to prevent further complications. This patient's ectropion and facial eczema may
      have been confounded by ocular rosacea. Exacerbation of 5-FU dermatologic
      toxicities in patients with preexisting conditions suggests the importance of
      aggressive ocular prophylaxis, using frequent ocular lubrication and topical
      steroid preparations with concurrent medical management of pre-existing
      dermatologic conditions. CONCLUSION: This case illustrates a potential link
      between dermatologic and ocular 5-FU toxicities. Further research and better
      communication among health care professionals are needed to determine if
      prophylaxis can reduce adverse ocular events.

PMID- 11243428
TI  - Reliability of rotary prism fusional vergence ranges.
AB  - BACKGROUND: The measurement of fusional vergence ranges is an important clinical
      test in the assessment of binocular vision status. Fusional vergence ranges are
      typically measured by recording a patient's reports of blur, break, and recovery
      to base-in (BI) and base-out (BO) prism. Published reliability data on fusional
      vergence ranges are very limited. METHODS: Eight subjects underwent four testing
      sessions, at which repeated measurements of fusional vergence ranges were taken.
      Near ranges were tested at the first session only Distance ranges were tested at
      all four sessions. Intra-examiner standard deviations were calculated for each
      fusional vergence test result (BI and BO; blur, break, and recovery) for each
      session. Intra-examiner standard deviations were averaged. These values were used
      to determine 95% limits of agreement. RESULTS: The 95% limits of agreement were
      between 2 delta and 2.5 delta for the distance BI break and recovery and for the
      near BI recovery; between 3 and 4 delta for near BI break and near BO break;
      between 4 and 5 delta for distance BO blur and recovery and for near BI blur; and
      between 5 and 5.5 delta for distance BO break and near BO blur and recovery.

PMID- 11243429
TI  - Medicare compliance in solo and small group practices.

PMID- 11243430
TI  - Improving staff performance using the appraisal process.

PMID- 11243431
TI  - A unique approac to low vision.

PMID- 11243432
TI  - Prescription for prevention.

PMID- 11243434
TI  - Research scientists are assuming more and more of the responsibilities of running
      optometry programs.

PMID- 11243433
TI  - Improving the U.S. health care system: what is the optometric role?

PMID- 11243435
TI  - Management of the Pulfrich phenomenon secondary to pigmentary glaucoma.
AB  - BACKGROUND: The Pulfrich phenomenon can cause annoying symptoms for a patient due
      to a difference in interocular optic nerve conduction. There are very few reports
      that describe the successful use of tinted lenses as a treatment modality, while
      the majority of cases in the literature describe the condition without any
      reference to treatment. Although there are two previous reported cases of the
      Pulfrich phenomenon secondary to glaucoma, this article relates the first case of
      a patient with this phenomenon with glaucoma treated by tinted lenses. CASE
      REPORT: A 42-year-old woman, who was previously diagnosed with asymmetric
      pigmentary glaucoma, reported dramatic changes in visual perception-especially
      with driving and motion-related tasks. The evaluation showed asymmetric optic
      nerve function and a spontaneous Pulfrich phenomenon. The effects of different
      grades of neutral-density filters over the better eye were quantified by means of
      the Pulfrich phenomenon, subjective brightness comparison, and the visual-evoked
      potential. Relief of some of the symptoms from the Pulfrich phenomenon was
      achieved using an ophthalmic tint. CONCLUSION: The majority of patients (89%)
      reported in the literature who are symptomatic of the Pulfrich phenomenon
      received no treatment. This report illustrates that the traditional optometric
      tool of tinted lenses can be dramatically effective in relief of the motion
      related symptoms secondary to the Pulfrich phenomenon in a patient with
      pigmentary glaucoma.

PMID- 11243436
TI  - Atopic dermatitis: a case report and current clinical review of systemic and
      ocular manifestations.
AB  - PURPOSE: Atopic dermatitis is a relatively common hereditary dermatologic
      condition. Ocular sequellae are commonly seen in this disorder and may include
      involvement of both the anterior and posterior segments of the eye. Clinical
      symptoms and presentation may vary, as well as visual prognosis. METHOD: A 48
      year-old black woman came to us with a sudden exacerbation of atopic disease with
      ocular complications-most notably, the classic "shield-like" anterior subcapsular
      cataract seen in patients with this disease. Extensive diagnostic and management
      considerations specific to this disorder are highlighted. RESULTS: A careful
      history and clinical examination will help direct appropriate diagnosis and
      management in this population. Although chronic in nature, acute exacerbations of
      the disease may require specific management. Proposed pathophysiologic
      mechanisms, including new aspects of treatment, are discussed. CONCLUSION: Ocular
      manifestations of atopic disease may be visually debilitating. Therefore,
      specific consideration relating to clinical course, effective diagnosis, and
      medical and surgical management of this disorder are discussed.

PMID- 11243437
TI  - Importation of wild poliovirus into Qinghai Province--China, 1999.
AB  - Indigenous wild poliovirus was last isolated in China in 1994. On October 13,
      1999, a case of acute flaccid paralysis (AFP) in a 16-month-old boy was reported
      to public health authorities in Xunhua Autonomous County, Haidong Prefecture,
      Qinghai Province, China. Following onset of paralysis on October 12, the boy was
      no longer able to stand or walk. Two stool samples, taken within 14 days of onset
      of paralysis, were analyzed in the Qinghai provincial laboratory and yielded
      poliovirus. The isolates were later differentiated as wild poliovirus type 1 at
      the National Poliovirus Laboratory in Beijing. Stool specimens from one of five
      children with whom the boy had contact yielded wild poliovirus type 1. This
      report describes this case of poliomyelitis and the public health response to the
      case in China.

PMID- 11243439
TI  - Information needs and uses of the  public health workforce--Washington, 1997
      1998.
AB  - Substantial efforts have been made to ensure that state and local public health
      agencies have the information technology and training needed for public health
      communications, information access, and data exchange. Numerous public health
      related data and information resources are available on the World-Wide Web (e.g.,
      MEDLINE, MMWR, CDC Prevention Guidelines Database, and Emerging Infectious
      Diseases); however, little systematic work has been done to understand the
      information needs of the public health workforce. To identify these needs and
      patterns of use and to set priorities for developing new online public health
      information resources, the University of Washington School of Public Health and
      Community Medicine (UW SPHCM) and the Washington State Department of Health
      (WSDoH) held structured and facilitated discussions with segments of the local
      public health workforce in Washington during 1997-1998. This report summarizes
      the results of those discussions, which indicate that different segments of the
      public health workforce have different information needs.

PMID- 11243438
TI  - Role of victims' services in improving intimate partner violence screening by
      trained maternal and child health-care providers--Boston, Massachusetts, 1994
      1995.
AB  - From 1992 to 1996, approximately 1 million incidents of nonfatal intimate partner
      violence (IPV) occurred each year in the United States; 85% of victims were
      women. In 1989, pediatric research found a concurrence of victimization of
      mothers and their children and supported a recommendation that maternal and child
      health-care providers (HCPs) pursue training and advocate for increased access to
      services to promote the safety and well-being of mothers and their children. From
      1992 to 1997, the Pediatric Family Violence Awareness Project (PFVAP), a training
      project for maternal and child HCPs, promoted prevention of and intervention for
      IPV in Massachusetts. In 1994, PFVAP conducted a pilot evaluation in two urban
      community health centers to determine whether HCPs trained to conduct IPV
      assessment would increase their screening rates of women at risk for IPV if an on
      site referral service for victims was available. This report summarizes the
      results of the pilot project, which indicate that IPV screening rates did not
      increase after implementing on-site victim service.

PMID- 11243445
TI  - Hypothermia-related deaths--Suffolk County, New York, January 1999-March 2000,
      and United States, 1979-1998.
AB  - Hypothermia is the unintentional lowering of core body temperature to <95 F (<35
      C). Core body temperature normally is maintained at 97.7 F (36.5 C). Most
      hypothermia-related deaths occur during the winter in states that have moderate
      to severe cold temperatures (e.g., Alaska, Illinois, New York, and Pennsylvania).
      During 1979-1998, New York had the second highest number of hypothermia-related
      deaths in the United States. This report presents case reports of four
      hypothermia-related deaths during January 1999-March 2000 in Suffolk County (1999
      population: 1,383,847), the largest county in New York excluding New York City,
      and summarizes hypothermia-related deaths in the United States during 1979-1998.
      Such deaths can be prevented by educating health-care providers and the public to
      identify persons at risk for hypothermia.

PMID- 11243446
TI  - Underdiagnosis of dengue--Laredo, Texas, 1999.
AB  - Dengue outbreaks have been reported in communities along the Mexico-U.S. border
      since 1980; however, during 1987-July 1999, no cases were reported from Laredo,
      Texas (1999 population: 162,000). During January-July 1999, approximately 300-325
      dengue cases were reported from Nuevo Laredo, Tamaulipas, Mexico (1999
      population: 274,000), a city across the Rio Grande from Laredo. To determine
      whether undiagnosed or unreported dengue cases had occurred in Laredo, the Texas
      Department of Health (TDH) reviewed medical records from five Laredo health
      facilities (the two city hospitals and the three largest of five community
      clinics). This report summarizes the findings of the review, which indicated that
      during July 23-August 20, 1999, 50% of suspected case-patients had undiagnosed
      dengue infection. Recognition of the diagnosis of dengue can be improved through
      heightened surveillance, professional and public education, and prompt reporting
      of cases by the health-care providers to local or state health departments.

PMID- 11243448
TI  - Ecological biochemistry and its development.
AB  - The concept that chemistry and biochemistry may play significant roles in
      ecological relationships is not a new one. It is only within the last quarter of
      a century, however, that this concept has gained general acceptance and
      ecological biochemistry has become a well defined interdisciplinary subject in
      its own right. Examples are given of different types of biochemical relationships
      involving plants and animals and reference to other areas of the subject are
      made.

PMID- 11243447
TI  - Injection practices among nurses--Valcea, Romania, 1998.
AB  - In the early 1990s, human immunodeficiency virus (HIV) infection associated with
      possible reuse of syringes and needles was reported among children in Romanian
      orphanages. These findings led health-care workers to use new disposable syringes
      and needles for administering injections. Bythe late 1990s, reports suggested
      that new disposable syringes and needles had become standard for all injections.
      However, surveillance data collected by the Romanian Ministry of Health (MoH)
      during 1997-1998 indicated that acute hepatitis B virus (HBV) infection was
      associated with receiving injections among children aged <5 years. In Romania,
      injection frequently is used to administer medication, and nurses administer most
      injections. To identify the practices that might have resulted in injection
      associated HBV transmission, selected clinic and hospital nurses were surveyed.
      This report summarizes the findings of the survey, which indicated that although
      nurses used new disposable syringes and needles, other inadequate infection
      control practices might explain injection-associated HBV transmission. Results of
      the survey were used by the Romanian Coalition to Prevent Nosocomial Infections
      to prepare standards for injection safety to protect patients and health-care
      workers from HBV infection.

PMID- 11243449
TI  - Contributions of Jeffrey Harborne and co-workers to the study of anthocyanins.
AB  - Jeffrey Harborne and his co-workers have played a unique role in the over-all
      study of plant pigments and of anthocyanins in particular through their many
      publications and through Jeffrey's editorial work with Phytochemistry. Jeffrey
      has made important contributions to our understanding of the separation and
      structural identification of anthocyanins; to co-pigmentation; and to the role of
      anthocyanins in systematics and ecology in both reproductive and vegetative
      tissues. This work has had considerable influence on much of the current research
      on the genetics and regulation of anthocyanin biosynthesis.

PMID- 11243450
TI  - Phytochemistry and medicinal plants.
AB  - A truncated history of the contribution of plants to medicine is given with
      reference to some of the less well known ancestors of the Harborne family. Six of
      the top 20 prescriptions dispensed in 1996 were natural products and the clinical
      use of drugs such as artemisinin, etoposide and taxol has once more focussed
      attention on plants as sources of novel drug entities. High through-put robotic
      screens have been developed by industry and it is possible to carry out 50,000
      tests per day in the search for compounds which have specificity of action
      against a key enzyme or a subset of receptors. Bioassay-guided fractionation of
      plant extracts linked to chromatographic separation techniques leads to the
      isolation of biologically active molecules whose chemical structures can readily
      be determined by modern spectroscopic methods. The role of academics in the
      search for new drugs is discussed by reference to some of our research into
      natural products with activity on the central nervous system, on pain receptors,
      the malaria parasite Plasmodium falciparum, the wound healing properties of the
      sap of species of Croton (Dragon's blood), and a traditional Chinese medicine
      used to treat eczema. Expertise in phytochemistry has been essential for this
      research and the strong lead shown by Professor Jeffrey Harborne is gratefully
      acknowledged.

PMID- 11243451
TI  - Importance of flavonoids in insect--plant interactions: feeding and oviposition.
AB  - Jeffrey Harborne and colleagues have been responsible for collating the majority
      of data on the role of flavonoids in insect plant interactions. This article
      examines some of this information and assesses our knowledge about the role
      flavonoids play in insect feeding and oviposition behaviour. It is clear that
      insects can discriminate among flavonoids and that these compounds can modulate
      the feeding and oviposition behaviour of insects, but further work is required to
      understand the neural mechanisms associated with these behavioural responses.
      Despite the wealth of data about the diversity of flavonoids in plants, very few
      of these compounds have been tested against insects and their role in the
      evolution of host range in insect--plant interactions has yet to be determined.

PMID- 11243452
TI  - Plant--fungal interactions: the search for phytoalexins and other antifungal
      compounds from higher plants.
AB  - A brief review is given of some biological, chemical and chemotaxonomic aspects
      of phytoalexin research. Emphasis is placed on the search for antifungal
      compounds in the plant families Leguminosae and Rosaceae, and in rice, Oryza
      sativa. The possible role of phytoalexins in the resistance of rice plants
      against the fungus Pyricularia oryzae (= Magnaporthe grisea) is discussed, and
      the future prospects of phytoalexin research are outlined.

PMID- 11243454
TI  - Recent advances in phytochemistry of bryophytes-acetogenins, terpenoids and
      bis(bibenzyl)s from selected Japanese, Taiwanese, New Zealand, Argentinean and
      European liverworts.
AB  - Bryophytes contain a large number of terpenoids and phenolic compounds. Recent
      topics relating to the chemical constituents found in 36 Japanese, 3 New Zealand,
      2 European, 1 Argentinean and 1 Taiwanese liverworts and 2 Japanese mosses and
      their biological activity are discussed. The chemosystematics of some liverworts
      as well as the chemical relationship between liverworts and mosses, and
      bryophytes and ferns are also discussed.

PMID- 11243453
TI  - Polyhydroxylated alkaloids -- natural occurrence and therapeutic applications.
AB  - Over one hundred polyhydroxylated alkaloids have been isolated from plants and
      micro-organisms. These alkaloids can be potent and highly selective glycosidase
      inhibitors and are arousing great interest as tools to study cellular recognition
      and as potential therapeutic agents. However, only three of the natural products
      so far have been widely studied for therapeutic potential due largely to the
      limited commercial availability of the other compounds.

PMID- 11243455
TI  - Cymbal array: a broad band sound projector.
AB  - A prototype 3 x 3 planar cymbal transducer array was built and tested. The array
      has a radiating area of 5.5 cm x 5.5 cm and a thickness of less than 8 mm. The
      measured transmitting voltage response was above 134 dB re 1 microPa/V @ 1 m and
      flat over the frequency range of 16 and 100 kHz. Array interaction was analyzed
      using an equivalent circuit model. The array interaction leads to variations in
      radiation resistance and velocity of the transducers in the array according to
      their surroundings in the array. The effect is enhanced overall efficiency and a
      flat response.

PMID- 11243456
TI  - A non-contact technique for evaluation of elastic structures at large stand-off
      distances: applications to classification of fluids in steel vessels.
AB  - A novel technique for non-contact evaluation of structures in air at large stand
      off distances (on the order of several meters) has been developed. It utilizes a
      recently constructed air-coupled, parametric acoustic array to excite the
      resonance vibrations of elastic, fluid-filled vessels. The parametric array is
      advantageous for NDE applications in that it is capable of producing a much
      narrower beamwidth and broader bandwidth than typical devices that operate under
      linear acoustic principles. In the present experiments, the array operates at a
      carrier frequency of 217 kHz, and the sound field several meters from the source
      is described spectrally by the envelope of the drive voltage. An operating
      bandwidth of more than 25 kHz at a center frequency of 15 kHz is demonstrated.
      For the present application, the array is used to excite vibrations of fluid
      filled, steel containers at stand-off distances of greater than 3 m. The
      vibratory response of a container is detected with a laser vibrometer in a
      monostatic configuration with the acoustic source. By analyzing the change in the
      response of the lowest order, antisymmetric Lamb wave as the interior fluid
      loading conditions of the container are changed, the fluid contained within the
      steel vessel is classified.

PMID- 11243457
TI  - Acoustic wave dispersion in a cylindrical elastic tube filled with a viscous
      liquid.
AB  - This paper deals with the study of the velocity and the attenuation of an
      acoustic wave propagating inside a cylindrical elastic tube filled with a viscous
      liquid. A theory describing the propagation of the axisymmetrical modes in such
      waveguides is presented, with special attention given to the absorption produced
      by the viscous mechanisms in the liquid. One of these mechanisms is related to
      the momentum transfer between the compression and rarefaction regions of a
      propagating wave. The other viscous mechanism is due to the momentum transport
      inside the viscous boundary layer, close to the tube wall. Numerical calculations
      were carried out to investigate the influence of different parameters (frequency,
      tube radii, viscosity coefficient) on the propagation of acoustic waves.

PMID- 11243458
TI  - Measurement of ultrasonic power and electro-acoustic efficiency of high power
      transducers.
AB  - In this paper, an improved method for the measurement of acoustic power and
      electro-acoustic efficiency of high power ultrasonic transducers is presented.
      The measuring principle is described, the experimental results are given. In
      comparison with traditional methods, the method presented in this paper has the
      advantages of simplicity, economy and practicality. The most important is that it
      can measure the output acoustic power and the electro-acoustic efficiency of the
      transducer under the condition of high power and practical applications, such as
      ultrasonic cleaning and soldering.

PMID- 11243459
TI  - Ultrasonic waves propagation in absorbing thin plates application to paper
      characterization.
AB  - Guided wave theory is applied to a thin orthotropic and absorbing plate for low
      frequency propagation of ultrasonic waves. The aim of this paper is to give some
      physical interpretations of the non-destructive characterization of paper
      materials, which are cellulosic fibrous networks. It is shown that the
      propagation problem reduces to two normal modes of propagation in the plane of
      the plate. Each of them depends on four complex and independent stiffnesses that
      are combinations of elementary complex stiffnesses of the media. The imaginary
      part of these stiffnesses corresponds to a possible mechanism of energy
      dissipation during the wave propagation for this kind of material. The reverse
      problem, which gives four complex values, is then numerically solved using a
      small attenuation assumption. The specially designed experimental set-up has led
      to the first measurements of tracing paper damping factors. The phase velocity
      measurements of the plate waves agree with the results already found by several
      paper researchers. As a particular and new result, the shear wave velocities are
      found to present a quasi-isotropic repartition in the plane of the paper sheet.
      It was found that the absorbing phenomenon can occur for each propagation mode in
      such a material. The attenuation values are small, except for one of them that
      corresponds to a coupling term in the propagation model. The anisotropy of their
      repartition is also shown in the case of quasi-longitudinal waves.

PMID- 11243460
TI  - Characterization of air-coupled ultrasound transducers in the frequency range 40
      kHz-2 mHz using light diffraction tomography.
AB  - The aim of this work was to show the applicability of light diffraction
      tomography on airborne ultrasound in the frequency range 40 kHz-2 MHz. Seven
      different air-coupled transducers were measured to show the method's performance
      regarding linearity, absolute pressure measurements, phase measurements,
      frequency response, S/N ratio and spatial resolution. A calibrated microphone and
      the pulse-echo method were used to evaluate the results. The absolute
      measurements agreed within the calibrated microphone's uncertainty range. Pulse
      waveforms and corresponding FFT diagrams show the method's higher bandwidth
      compared with the microphone. Further, the method offers non-perturbing
      measurements with high spatial resolution, which was especially advantageous for
      measurements close to the transducer surfaces. The S/N ratio was higher than or
      in the same range as that of the two comparison methods.

PMID- 11243462
TI  - Study and fabrication of the PbTiO3 thin film acoustic sensors.
AB  - In this study, thin film acoustic sensors were fabricated utilizing the r.f.
      planar magnetron sputtering method and micromachining techniques. Underwater
      testing results indicated that the maximum receiving sensitivity of -117.8 dBV
      microbar(-1) occurred at 5.5 MHz. For the acoustic sensors tested, the highest
      transmitting intensities were 26.5 dBV/microbar at a fundamental resonant
      frequency of 7 MHz, 40.4 dBV microbar(-1) at the third harmonic of 21 MHz, and
      37.1 dBV microbar(-1) at half the fundamental frequency or 3.5 MHz. Underwater
      measurements also indicated that the larger the sample area, the higher the
      transmitting intensity and receiving sensitivity.

PMID- 11243461
TI  - Two-dimensional modelling of multifrequency piezocomposites.
AB  - The multifrequency composites of 2-2 connectivity modelled in this work are made
      with groups of piezoelectric elements of different lateral dimensions,
      periodically reproduced in the structure. These composites have potential to
      improve the performances of standard piezoelectric composites with the same
      materials and ceramic fraction, on account that they have different resonators
      coupled mechanically along the structure. A one-dimensional model was developed
      to study their performances in a first approximation. In order to obtain a design
      model, a two-dimensional model, previously used to describe multielement array
      transducers, has been extended to the case of 2-2 polymer-piezoceramic
      composites. Several composite samples, having piezoceramic strips with different
      width-to-thickness ratios, have been built, and their resonance behaviour
      compared with the model prediction. Finally, the model has been extended to the
      case of 2-2 multifrequency composites. For multifrequency composites having in
      the same composite structure two or three piezoceramic strips with different
      lateral dimensions, the comparison between experimental and predicted results
      shows good agreement. The model has been used to optimise a double composite in
      comparison with a standard one with the same volume fraction and constituents.

PMID- 11243463
TI  - Design of a self-calibrating simulated acoustic emission source.
AB  - The use of conical piezoelectric transducers as point acoustic sources has been
      investigated. It has been shown that transducers based on a design originally
      developed at the National Institute for Standards and Technology in the USA can
      be used as point transmitters over the frequency range of interest in acoustic
      emission measurements (100 kHz to around 1 MHz). They should, therefore, be
      suitable for use in experiments to calibrate structures so that acoustic emission
      source strengths can be determined. It has also been shown that measurements of
      the response of the transmitting transducer backing can be used to assess the
      coupling efficiency, and hence to remove concerns about inconsistent coupling
      affecting the calibration measurements. The results indicate that the variation
      of the backing response with coupling is due to a shift in the resonance
      frequencies of the transducer with the mechanical load impedance. If other
      transducers can be shown to behave in a similar fashion this effect could be used
      to measure coupling in standard acoustic emission and ultrasonic transducers.

PMID- 11243464
TI  - Thickness measurement in composite materials using lamb waves viscoelastic
      effects.
AB  - Pulse propagation in plates has been investigated with the identification of Lamb
      modes. The application of this technique to the measurement of thickness in
      composite and coarse materials was previously evaluated. As a sequel, results of
      the application of this technique taking into account the viscoelastic properties
      of PVC and ferrocement are presented.

PMID- 11243465
TI  - Inhibition of transforming growth factor beta signaling in MCF-7 cells results in
      resistance to tumor necrosis factor alpha: a role for Bcl-2.
AB  - Transforming growth factor beta (TGF-beta) is a multifunctional cytokine capable
      of regulating diverse cellular processes. In this study we investigated the
      effect of autocrine TGF-beta signaling on tumor necrosis factor (TNF) alpha
      induced cell death. We abrogated the TGF-beta autocrine loop by overexpression of
      a truncated TGF-beta type II receptor in MCF-7 breast carcinoma cells and found
      that this generated resistance to TNF-alpha-induced cytotoxicity. To elucidate
      the molecular basis of the influence of TGF-beta on TNF-alpha-induced
      cytotoxicity, we evaluated the expression levels or activities of proteins
      involved in TNF-alpha signal transduction or the regulation of apoptosis in
      general in TGF-beta-responsive and TGF-beta-nonresponsive MCF-7 cells. We
      observed no significant difference in the expression of TNF-alpha receptors or
      the TNF receptor-associated death domain protein. In addition, downstream
      activation of nuclear factor kappaB by TNF-alpha was not altered in cells that
      had lost TGF-beta responsiveness. Analysis of members of the Bcl-2 family of
      apoptosis-regulatory proteins revealed that Bcl-X(L) and Bax expression levels
      were not changed by disruption of TGF-beta signaling. In contrast, the TGF-beta
      nonresponsive cells expressed much higher levels of Bcl-2 protein and mRNA than
      did cells with an intact TGF-beta autocrine loop. Furthermore, restoration of a
      TGF-beta signal to MCF-7 cells that had spontaneously acquired resistance to TGF
      beta caused a reduction in Bcl-2 protein expression. Taken together, our data
      indicate that loss of autocrine TGF-beta signaling results in enhanced resistance
      to TNF-alpha-mediated cell death and that this is likely to be mediated by
      derepression of Bcl-2 expression.

PMID- 11243466
TI  - Autocrine transforming growth factor beta suppresses telomerase activity and
      transcription of human telomerase reverse transcriptase in human cancer cells.
AB  - Because autocrine transforming growth factor beta (TGF-beta) can suppress
      carcinogenesis, which is often associated with telomerase activation, we studied
      whether autocrine TGF-beta inhibits telomerase activity. Restoration of autocrine
      TGF-beta activity in human colon carcinoma HCT116 cells after reexpression of its
      type II receptor (RII) led to a significant reduction of telomerase activity and
      the mRNA level of telomerase reverse transcriptase (hTERT), whereas suppression
      of the autocrine TGF-beta activity with a dominant negative RII without the
      cytoplasmic domain (deltaRII) in human breast cancer MCF-7 cells led to a
      significant increase of telomerase activity and hTERT mRNA level. This appears to
      be due to repression of hTERT mRNA transcription because exogenous TGF-beta
      treatment of MCF-7 cells transiently transfected with a hTERT promoter-reporter
      construct significantly repressed the hTERT promoter activity in a dose-dependent
      manner. Furthermore, the hTERT promoter activity was significantly decreased in
      HCT116 RII cells and increased in MCF-7 deltaRII cells when compared with their
      respective controls. Therefore, autocrine TGF-beta appears to target hTERT
      promoter to inhibit telomerase activity.

PMID- 11243467
TI  - Gene array analysis of osteoblast differentiation.
AB  - We have used gene array technology to chart changes in gene expression during
      differentiation of the mouse calvarial-derived MC3T3-E1 cell line to an
      osteoblast-like phenotype. Expression was analyzed on a mouse gene array panel of
      588 cDNAs representing tightly regulated genes with key roles in various
      biological processes. When compared with NIH3T3 fibroblasts, MC3T3-E1 cells
      showed generally higher expression of cyclins and Bcl-2 family members, as well
      as specific expression of products such as the CD44 antigen, which is consistent
      with their calvarial origin. MC3T3-E1 cells also showed a surprisingly high level
      of p53. Differentiation in MC3T3-E1 cells involves withdrawal from the cell cycle
      by day 7, accompanied by matrix accumulation and, ultimately, mineralization.
      Gene expression patterns in induced MC3T3-E1 cells generally reflected these
      stages. Cyclins were sharply down-regulated, and expression of certain
      antiproliferative factors and tissue-restricted genes was induced. Many of the
      observed changes, such as the induction of follistatin, bone morphogenetic
      protein receptor 1A, transforming growth factor beta, and matrix remodeling
      factors, reflect expected patterns and support the physiological relevance of the
      results. Other observed changes were not anticipated and offer new insight into
      the osteoblast differentiation process. An example is the sharp induction of the
      Tob antiproliferative factor, which has previously been associated specifically
      with terminal differentiation in muscles. Another example is the induction of the
      DNA damage-associated proteins EI24 and Gadd45, apparently as a normal aspect of
      osteoblast differentiation. The oxidative stress-induced protein A170 and the
      transcription factor Nrf2, which regulates metabolic responses to oxidative
      stress, were also induced. This response may reflect the in vivo requirement for
      vascularization during bone growth and fracture repair. Other induced factors
      include tumor necrosis factor receptor-associated factor-1 (1-TRAF), which is a
      nuclear factor kappaB activator, cellular retinoic acid-binding protein II (CRABP
      II), and the transcription factors S-II, SP2, and SEF2 (ITF2/E2:2). SEF2 is the
      first basic helix-loop-helix protein found to be up-regulated during osteoblast
      differentiation. Northern blots confirm the induction of SEF2.

PMID- 11243470
TI  - Influence of the radial and vertical dimensions on lateral neglect.
AB  - The influence of radial (near-far) and vertical (upper-lower) dimensions on
      lateral visuo-spatial neglect was studied using two horizontal line-bisection
      tasks (one motor and one perceptual). A group of 15 patients with neglect and a
      group of 14 right-brain damaged patients without neglect were examined. This
      latter group was used to define the range of variability in line-bisection
      performance that was independent of neglect. For the radial dimension, some
      neglect patients showed greater errors in far space than in near space (for both
      stimuli presented in the upper and lower space). Fewer patients showed the
      opposite pattern (i.e., greater errors for near-space stimuli). These near-far
      asymmetries were present for both the motor and perceptual conditions and showed
      a good degree of intra-individual consistency. This finding contradicts the
      hypothesis that the motor component is critical for yielding such asymmetry. For
      the vertical dimension, the results indicated that neglect patients make more
      bisection errors for lower-space stimuli than for upper-space stimuli. This
      vertical asymmetry was nearly always confined to stimuli in near space.
      Asymmetries along the vertical dimension were present for both perceptual and
      motor conditions, although intra-individual consistency was low. When perceptual
      and motor conditions were directly compared, several neglect patients showed
      greater errors in the perceptual than in the motor task.

PMID- 11243469
TI  - Integrin expression and usage by prostate cancer cell lines on laminin substrata.
AB  - During prostate cancer progression, invasive glandular epithelial cells move out
      of the ductal-acinar architecture and through the surrounding basement membrane.
      Extracellular matrix proteins and associated soluble factors in the basal lamina
      and underlying stroma are known to be important regulators of prostate cell
      behaviors in both normal and malignant tissues. In this study, we assessed cell
      interactions with extracellular matrix and stromal factors during disease
      progression by characterizing integrin usage and expression in a series of
      parental and lineage-derived LNCaP human prostate cancer cell lines. Although few
      shifts in integrin expression were found to accompany disease progression,
      integrin heterodimer usage did change significantly. The more metastatic sublines
      were distinct in their use of alphavbeta3 and, when compared with parental LNCaP
      cells, showed a shift in alpha6 heterodimerization, a subunit critical not only
      for interaction with prostate basal lamina but also for interaction with the bone
      matrix, a favored site of prostate cancer metastases.

PMID- 11243468
TI  - DNA recognition by the aberrant retinoic acid receptors implicated in human acute
      promyelocytic leukemia.
AB  - Human acute promyelocytic leukemias (APLs) are associated with chromosomal
      translocations that replace the NH2 terminus of wild-type retinoic acid receptor
      (RAR) alpha with portions of the promyelocytic leukemia protein (PML) or
      promyelocytic leukemia zinc-finger protein (PLZF). The wild-type RARalpha readily
      forms heterodimers with the retinoid X receptors (RXRs), and these RAR/RXR
      heterodimers appear to be the principal mediators of retinoid signaling in normal
      cells. In contrast, PML-RARalpha and PLZF-RARa display an enhanced ability to
      form homodimers, and this enhanced homodimer formation is believed to contribute
      to the neoplastic properties of these chimeric oncoproteins. We report here that
      the DNA recognition specificity of the RXRalpha/RARa heterodimer, which is
      presumed to be the dominant receptor species in normal cells, differs from that
      of the PML-RARalpha and PLZF-RARalpha homodimers, which are thought to prevail in
      the oncogenic cell. We suggest that differences in target gene recognition by the
      normal and oncogenic RARalpha proteins may contribute to the leukemogenic
      phenotype.

PMID- 11243471
TI  - Time course and temporal order of changes in movement kinematics during motor
      learning: effect of joint and instruction.
AB  - Learning a motor task is associated with specific changes in movement kinematics.
      Recently, it has been shown that changes in different kinematic parameters
      occurred with different time courses for subjects who practiced simple, single
      joint elbow movements. For example, movement time was seen to decrease and level
      off in a shorter time than peak velocity, which increased and plateaued later.
      What is not known, however, is whether the time course and temporal order of
      these learning-related changes seen at the elbow are similar for movements
      learned at other joints and with different instructions. In this study,
      neurologically normal subjects practiced 50 degrees -flexion movements made at
      the wrist, with the instruction to be both "fast and accurate" (same instruction
      used in the earlier elbow study). A different group of subjects practiced wrist
      movements of the same amplitude, but with instructions to make movements that
      were "always accurate;" only as movement skill developed could subjects increase
      their speed (but without ever sacrificing accuracy). We measured time-related
      parameters (duration of acceleration, duration of deceleration, and total
      movement duration) and magnitude-related parameters (peak velocity, peak
      acceleration, and peak deceleration). We found that the time course of changes in
      kinematic parameters for subjects instructed to be "fast and accurate" was
      similar to that reported at the elbow. When the instruction was changed to be
      "always accurate," the time for changes in kinematic parameters to level off was
      found to be longer. However, regardless of instruction, time-related parameters
      plateaued before magnitude-related parameters. Thus, our results indicate that
      motor learning mechanisms may operate in a similar way at different joints.

PMID- 11243472
TI  - Withdrawal reflex organisation to electrical stimulation of the dorsal foot in
      humans.
AB  - The present study investigated excitatory reflex receptive fields for various
      muscle reflex responses and reflex mediated ankle joint movements using
      randomised electrical stimulation of the dorsal and plantar surface of the foot
      in 12 healthy subjects. Eleven electrodes (0.5-cm2 cathodes) were mounted on the
      dorsal side and three on the plantar side of the foot. A low (1.5 times pain
      threshold) and a high (2.3 times pain threshold) stimulus intensity were used to
      elicit the reflexes. EMG signals were recorded from tibialis anterior (TA),
      gastrocnemius medialis (GM), soleus (SO), biceps femoris (BF), and rectus femoris
      (RF) muscles together with the ankle movement measured by a goniometer. The
      withdrawal pattern evoked from the dorsal side consisted of two separate
      responses with different receptive fields: (1) early EMG responses in GM and BF
      (50-120 ms) evoking knee flexion, probably of purely spinal origin, and (2) a
      late response in GM and SO (120-200 ms) that may be under supraspinal control.
      The ankle flexor TA was significantly activated in both time windows, but in 11
      of 12 subjects its contraction was too small to cause significant dorsal flexion.
      In the ankle joint inversion was the most dominant movement. Stimulation of the
      plantar side resulted in activation of TA when stimulating the forefoot and in
      activation of triceps surae when stimulating the heel. These observations show
      that painful stimuli activate appropriate muscles depending on stimulus location
      to initiate the adequate withdrawal. For proximal muscles (e.g. knee flexors) the
      receptive field covers almost the entire foot (dorsal and plantar sides) while
      more distal muscles have a smaller receptive field covering only a part of the
      foot. This adequate withdrawal movement suggests a more refined withdrawal reflex
      organisation than a stereotyped flexion of all joints to avoid tissue damage.

PMID- 11243473
TI  - Enhanced neurogenesis after transient global ischemia in the dentate gyrus of the
      rat.
AB  - The dentate gyrus is one of the few areas of the mammalian brain where new
      neurons are continuously produced in adulthood. Certain insults such as epileptic
      seizures and ischemia are known to enhance the rate of neuronal production. We
      analyzed this phenomenon using the temporary occlusion of the two carotid
      arteries combined with arterial hypotension as a method to induce ischemia in
      rats. We measured the rate of cell production and their state of differentiation
      with a mitotic indicator, bromodeoxyuridine (BrdU), in combination with the
      immunohistochemical detection of neuronal markers. One week after the ischemic
      episode, the cell production in dentate gyrus was increased two- to threefold
      more than the basal level seen in control animals. Two weeks after ischemia, over
      60% of these cells became young neurons as determined by colabeling with BrdU and
      a cytoplasmic protein (CRMP-4) involved in axonal guidance during development.
      Five weeks after the ischemia, over 60% of new neurons expressed calbindin, a
      calcium-binding protein normally expressed in mature granule neurons. In addition
      to more cells being generated, a greater proportion of all new cells remained in
      the differentiated but not fully mature state during the 2- to 5-week period
      after ischemia. The maturation rate of neurons as determined by the calbindin
      labeling and by the rate of migration from a proliferative zone into the granule
      cell layer was not changed when examined 5 weeks after ischemia. The results
      support the hypothesis that survival of dentate gyrus after ischemia is linked
      with enhanced neurogenesis. Additional physiological stimulation after ischemia
      may be exploited to stimulate maturation of new neurons and to offer new
      therapeutic strategies for promoting recovery of neuronal circuitry in the
      injured brain.

PMID- 11243474
TI  - Is writer's cramp caused by a deficit of sensorimotor integration?
AB  - Writer's cramp is a highly specific movement disorder in which handwriting is
      impaired while most other manual skills are often unaffected. On the basis of
      abnormal findings in experiments measuring the control of grip forces, it has
      been suggested that writer's cramp is caused by a deficit of sensorimotor
      integration. The aim of our study was to determine whether there is a functional
      link between sensory deficits, abnormalities in the control of grip force, and
      handwriting disorders. We compared the grip force and handwriting performance of
      writer's cramp patients with that of control subjects and with that of a stroke
      patient suffering a purely somatosensory deficit of his dominant hand (patient
      S1). We found that: (1) writer's cramp patients and patient S1 had elevated grip
      force levels; (2) training reduced the grip force to near-normal levels in all
      writer's cramp patients but not in S1; (3) effortful writing performance also
      induced increased grip-force levels in healthy subjects; and (4) patient S1 had
      normal handwriting movements. These findings suggest that the elevated
      pretraining gripforce levels of writer's cramp patients might be a consequence of
      their effortful writing style and do not reflect a deficit of sensorimotor
      integration. Moreover, the good handwriting performance of patient S1 shows that
      a severe somatosensory deficit is not a sufficient condition for a handwriting
      disorder. These findings disagree with the sensorimotor explanation of writer's
      cramp.

PMID- 11243475
TI  - Tapping with peripheral nerve block. a role for tactile feedback in the timing of
      movements.
AB  - This study examines the impact of peripheral nerve block, that is, the
      elimination of tactile feedback on synchronization performance. In a tapping
      experiment in which subjects were instructed to tap in synchrony with an auditory
      pacing signal, three different tasks were studied under conditions with and
      without peripheral nerve block: standard tapping with tactile contact, isometric
      tapping, and contact-free tapping. In addition, the maximum tapping rate was
      registered both with and without peripheral nerve block. It was found that the
      anticipatory error, usually observed in synchronization tasks, was affected by
      the peripheral nerve block in the standard tapping and the isometric tapping
      task. In both tasks, local anesthesia led to an increase in asynchrony between
      the pacing signal and the tap. Performance remained unimpaired in those tasks in
      which tactile information was assumed to play a minor role (maximum tapping rate
      and contact-free tapping). The results clearly demonstrate the importance of
      tactile feedback for the timing of movements. The predictions of a model assuming
      a strong correlation between the amount of sensory feedback and the size of the
      negative asynchrony in synchronization tasks were examined and discussed.

PMID- 11243476
TI  - The development of balance control in children: comparisons of EMG and kinetic
      variables and chronological and developmental groupings.
AB  - This cross-sectional study examined electromyographic (EMG) and kinetic variables
      during reactive balance responses in children grouped according to developmental
      level as compared with chronological age. Purposes were to explore relationships
      between the two types of variables and the effectiveness of the two grouping
      methods. Forty-four children between 9 months and 10 years old were tested for
      reactive balance control on a moveable platform. Surface electrodes measured EMG
      activity in the gastrocnemius (GA), hamstrings (HA), paraspinals (PS), tibialis
      anterior (TA), quadriceps (QA), and abdominal (AB) muscles. Timing and distance
      of center-of-pressure (COP) movements and peak muscle torques at the ankle, knee,
      and hip were also examined. Significant relationships and group differences were
      found between postural muscle activity and both the torque generated in the lower
      limbs and the timing and distance of COP adjustments employed to restabilize
      balance. As postural muscle activity increased and became more coordinated in
      timing, peak torque at the ankle and hip also increased, while the distance of
      and time to complete COP readjustments decreased. Children in
      younger/developmentally lower groups had smaller-magnitude and less-synergic
      muscle activity, lower peak torques, longer times to restabilize the COP, and
      greater COP paths than older/higher developmental groupings. Grouping by
      developmental level produced more statistical differences than did grouping by
      age. The correspondence of GA, HA, and PS muscle activity with COP measures and
      joint peak torques confirms that these muscles are key contributors to the
      balance synergy correcting for induced forward sway. Additionally, developmental
      level appears to be a much better predictor of balance improvement than
      chronological age.

PMID- 11243477
TI  - Aging of the trigeminal blink system.
AB  - This study characterizes trigeminal blinks in normal human subjects between 20
      and 80 years of age, 60-year-old Parkinson's disease patients, and young and old
      guinea pigs. In normal humans over 60 years of age, lid-closing duration, and the
      excitability and latency of the trigeminal reflex blink increase significantly
      relative to younger subjects. Aged guinea pigs appear to display similar
      increases in reflex blink duration and latency. Reflex blink amplitude, however,
      does not change consistently with age. For subjects less than 70 years of age, a
      unilateral trigeminal stimulus evokes a 37% larger blink in the eyelid
      ipsilateral to the stimulus than in the contralateral eyelid, but 70-year-olds
      exhibit blinks of equal amplitude. In all cases, blink duration is identical for
      the two eyelids. If normal, age-related loss of dopamine neurons explains these
      trigeminal blink modifications, then Parkinson's disease should exaggerate age
      related changes in these blink parameters. Preliminary data show that Parkinson's
      disease increases blink duration and excitability relative to age-matched control
      subjects. Thus, it seems likely that normal, age-related loss of dopamine neurons
      accounts for increases in trigeminal blink excitability and duration. A
      previously uncharacterized type of trigeminally evoked blink appears after age 40
      in humans and in aged guinea pigs. In subjects less than 40 years old, a single
      trigeminal stimulus elicits a single reflex blink. In subjects over age 40,
      however, a single stimulus frequently evokes a reflex blink and additional blinks
      that occur at a fixed interval relative to the preceding blink. These "blink
      oscillations" may arise from oscillatory processes within trigeminal reflex blink
      circuits. The presence of exaggerated blink oscillations in subjects with dry eye
      and benign essential blepharospasm suggests that an alteration of blink
      oscillation mechanisms plays a critical role in these disorders.

PMID- 11243478
TI  - Selective effect of closed-head injury on central resource allocation: evidence
      from dual-task performance.
AB  - Two dual-task experiments are reported bearing on the issue of slower processing
      time for severe chronic closed-head injury (CHI) patients compared to matched
      controls. In the first experiment, a classical psychological refractory period
      (PRP) paradigm was employed, in which two sequential stimuli, a pure tone and a
      colored dot, were presented at variable stimulus onset asynchronies (SOAs), each
      associated with a distinct task. The task on the tone required a speeded vocal
      response based on pitch, and the task on the colored dot required a speeded
      manual response based on color. In the second experiment, either one or three
      masked letters was presented, followed by a pure tone at variable SOAs. The task
      on the letters required a delayed report of the letters at the end of each trial.
      The task on the tone required an immediate manual response based on pitch. In
      both experiments, both CHI patients and matched controls reported an SOA-locked
      slowing of the speeded response to the second stimulus, a PRP effect. The PRP
      effect was more substantial for CHI patients than for matched controls,
      suggesting that a component of the slower processing time for CHI patients was
      related to a selective increase in temporal demands for central processing of the
      stimuli.

PMID- 11243479
TI  - Vertical gaze angle: absolute height-in-scene information for the programming of
      prehension.
AB  - One possible source of information regarding the distance of a fixated target is
      provided by the height of the object within the visual scene. It is accepted that
      this cue can provide ordinal information, but generally it has been assumed that
      the nervous system cannot extract "absolute" information from height-in-scene. In
      order to use height-in-scene, the nervous system would need to be sensitive to
      ocular position with respect to the head and to head orientation with respect to
      the shoulders (i.e. vertical gaze angle or VGA). We used a perturbation technique
      to establish whether the nervous system uses vertical gaze angle as a distance
      cue. Vertical gaze angle was perturbed using ophthalmic prisms with the base
      oriented either up or down. In experiment 1, participants were required to carry
      out an open-loop pointing task whilst wearing: (1) no prisms; (2) a base-up
      prism; or (3) a base-down prism. In experiment 2, the participants reached to
      grasp an object under closed-loop viewing conditions whilst wearing: (1) no
      prisms; (2) a base-up prism; or (3) a base-down prism. Experiment 1 and 2
      provided clear evidence that the human nervous system uses vertical gaze angle as
      a distance cue. It was found that the weighting attached to VGA decreased with
      increasing target distance. The weighting attached to VGA was also affected by
      the discrepancy between the height of the target, as specified by all other
      distance cues, and the height indicated by the initial estimate of the position
      of the supporting surface. We conclude by considering the use of height-in-scene
      information in the perception of surface slant and highlight some of the
      complexities that must be involved in the computation of environmental layout.

PMID- 11243480
TI  - Effector-dependent acquisition of novel typing sequences.
AB  - In an earlier report we found that when pairs of letters were physically
      transposed on the keyboard and typists were required to type letters in their new
      location, the disruptions in typing were reduced when the transpositions involved
      mirror movements of homologous fingers of the two hands compared with
      transpositions involving the same hand. We hypothesized that acquisition may be
      facilitated when a new movement mirrors a previously learned movement. In order
      to test this hypothesis, in the present study we transposed various pairs of
      letters between the two hands. Experienced typists (n = 6) typed phrases in which
      a key was physically transposed with another key on the keyboard and subjects
      typed the letters in their new location (for 200 trials). The pairs of
      transpositions involved: (1) similar movements of homologous fingers; (2)
      different movements of homologous fingers; (3) similar movements of non
      homologous fingers; and (4) different movements of non-homologous fingers. After
      the transposition of keys, there were non-uniform prolongations in the typing
      intervals of words containing transposed keys, with the largest delay occurring
      directly before the transposition. Practice had a differential effect on these
      intervals; some key press intervals achieved control levels, while others did not
      improve at all. The disruptions in typing were dependent on the specific keys
      transposed. Transpositions involving non-homologous digits of the two hands were
      less disruptive than transpositions involving homologous digits. The results do
      not support our earlier hypothesis that acquisition may be facilitated when a new
      movement mirrors a previously learned one. These results provide some possible
      insights into how distinct levels of movement organization develop in typing as a
      result of practice. Furthermore, the non-uniformity of the typing intervals in
      the words containing transposed keys supports the notion that typing is organized
      at multiple levels, including the individual key press and word level.

PMID- 11243481
TI  - Is the response pattern of on- and off-cells in the rostral ventromedial medulla
      to noxious stimulation independent of stimulation site?
AB  - The classification of on- and off-cells in the rostral ventromedial medulla is
      based on the response pattern to noxious tail heat. It is generally assumed that
      on- and off-cells respond equally to noxious stimulation anywhere on the body
      surface, but so far this assumption has not been systematically examined. In the
      present study the effects of noxious thermal and mechanical stimuli applied to
      the tail, the extremities and the craniofacial region on the extracellularly
      recorded activity of 13 on- and 23 off-cells were investigated in lightly
      anesthetized rats. In 3 out of 13 on-cells and 11 out of 23 off-cells the
      response pattern evoked by noxious stimulation of the extremities or the
      craniofacial region differed from the response pattern elicited by noxious tail
      heat. In comparison with the response pattern to noxious tail heat, stimulation
      of the extremities or the craniofacial region reproducibly evoked opposite
      reactions in 2 on- and 9 off-cells and did not change neuronal activity in one on
      and 2 off-cells. The results of the present study raise the question of whether
      the response pattern of on- and off-cells in the rostral ventromedial medulla can
      be sufficiently predicted by a classification that is exclusively based on the
      cellular behavior to noxious heat stimulation of the tail.

PMID- 11243482
TI  - The influence of age on weight-bearing joint reposition sense of the knee.
AB  - Knee joint-position sensitivity has been shown to decline with increasing age,
      with much of the research reported in the literature investigating this age
      effect in non-weight-bearing (NWB) conditions. However, little data is available
      in the more functional position of weight-bearing conditions. The objective of
      this study was to identify the influence of age on the accuracy and nature of
      knee joint-position sense (JPS) in both full weight-bearing (FWB) and partial
      weight-bearing (PWB) conditions and to determine the effect of lower-extremity
      dominance on knee JPS. Sixty healthy subjects from three age groups (young: 20-35
      years old, middle-aged: 40-55 years, and older: 60-75 years) were assessed. Tests
      were conducted on both the right and left legs to examine the ability of subjects
      to correctly reproduce knee angles in an active criterion-active repositioning
      paradigm. Knee angles were measured in degrees using an electromagnetic tracking
      device, Polhemus 3Space Fastrak, that detected positions of sensors placed on the
      test limb. Errors in FWB knee joint repositioning did not increase with age, but
      significant age-related increases in knee joint-repositioning error were found in
      PWB. It was found that elderly subjects tended to overshoot the criterion angle
      more often than subjects from the young and middle-aged groups. Subjects in all
      three age groups performed better in FWB than in PWB. Differences between the
      stance-dominant (STD) and skill-dominant (SKD) legs did not reach significance.
      Results demonstrated that for, normal pain-free individuals, there is no age
      related decline in knee JPS in FWB, although an age effect does exist in PWB.
      This outcome challenges the current view that a generalised decline in knee joint
      proprioception occurs with age. In addition, lower-limb dominance is not a factor
      in acuity of knee JPS.

PMID- 11243483
TI  - Let your feet do the walking: constraints on the stability of bipedal
      coordination.
AB  - In this paper we consider whether the behaviour of the neural circuitry that
      controls lower limb movements in humans is shaped primarily by the spatiotemporal
      characteristics of bipedal gait patterns, or by selective pressures that are
      sensitive to considerations of balance and energetics. During the course of
      normal locomotion, the full dynamics of the neural circuitry are masked by the
      inertial properties of the limbs. In the present study, participants executed
      bipedal movements in conditions in which their feet were either unloaded or
      subject to additional inertial loads. Two patterns of rhythmic coordination were
      examined. In the in-phase mode, participants were required to flex their ankles
      and extend their ankles in synchrony. In the out-of-phase mode, the participants
      flexed one ankle while extending the other and vice versa. The frequency of
      movement was increased systematically throughout each experimental trial. All
      participants were able to maintain both the in-phase and the out-of-phase mode of
      coordination, to the point at which they could no longer increase their frequency
      of movement. Transitions between the two modes were not observed, and the
      stability of the out-of-phase and in-phase modes of coordination was equivalent
      at all movement frequencies. These findings indicate that, in humans, the
      behaviour of the neural circuitry underlying coordinated movements of the lower
      limbs is not constrained strongly by the spatiotemporal symmetries of bipedal
      gait patterns.

PMID- 11243484
TI  - CRT screens may give rise to biased estimates of interhemispheric transmission
      time in the Poffenberger paradigm.
AB  - It has been shown that computer video-display units do not emit luminance
      uniformly over the entire screen, but emit more light on the right hand side than
      on the left hand side. The present study investigates whether this luminance
      asymmetry has implications for the manual and vocal estimates of interhemispheric
      transmission time (IHTT) in the Poffenberger paradigm. In particular, it is shown
      that previous reports of right visual-field advantages for vocal responses are an
      artifact of the luminance asymmetry of computer screens and that this asymmetry
      also has implications for estimates of differences in transmission time from the
      right to the left hemisphere in manual responses. In addition, we examined the
      impact of stimulus intensity and dark adaptation to the IHTT estimates and found
      that neither had an effect. This is in line with previous evidence that
      interhemispheric transfer in the Poffenberger paradigm does not depend on the
      transfer of visual information.

PMID- 11243485
TI  - Dissociation of grip/load-force coupling during a bimanual manipulative
      assignment.
AB  - The aim of the present study was to examine interlimb interactions of grasping
      forces during a bimanual manipulative assignment that required the execution of a
      drawer-opening task with the left hand and an object-holding task with the right
      hand. Compared with the unimanual performance, the grip/load-force ratio of the
      object-holding task was shifted towards that of the simultaneously executed
      drawer-opening task. This shows that force parameterization of the dynamic
      activity interacted with that of the static activity. That the increased force
      ratio only involved modification of grip force, while load force was held
      constant, indicates a disruption of the commonly observed co-variation of both
      forces during a manipulative action. These data are consistent with the notion
      that the coordinative constraint between grip and load force is a flexible
      parameter.

PMID- 11243486
TI  - Landmark publications in Psychopharmacology: the first 40 years.

PMID- 11243487
TI  - St. John's wort (Hypericum perforatum): a review of the current pharmacological,
      toxicological, and clinical literature.
AB  - RATIONALE: St. John's wort (Hypericum perforatum) has recently gained popularity
      as an alternative treatment for mild to moderate depression. Given the current
      widespread use of this herbal remedy, it is important for medical professionals
      to understand the potential pharmacological pathways through which Hypericum may
      exert an antidepressant effect. OBJECTIVES: (1) To review the current
      pharmacological, toxicological, and clinical literature available on Hypericum,
      and (2) to provide a synthesis of this information into a form that may be easily
      used by health care providers. METHOD: A comprehensive review of the recent
      scientific literature (January 1990-March 2000) was performed using the following
      electronic databases and reference publications: MEDLINE, The Cochrane Library,
      HealthSTAR, Current Contents (all editions), European Scientific Cooperative on
      Phytotherapy monographs, German Commission E monographs, and the Physicians' Desk
      Reference for Herbal Medicines, 1st edition. RESULTS: One hundred and seven (107)
      publications in the English language and three publications in German were
      included in the review. Collectively, the data suggest that therapeutic
      preparations of Hypericum extract appear to exert potentially significant
      pharmacological activity within several neurochemical systems believed to be
      implicated in the pathophysiology of depression. However, little information
      exists regarding the safety of Hypericum, including potential herb-drug
      interactions. CONCLUSIONS: Additional research on the pharmacological and
      biochemical activity of Hypericum and its several bioactive constituents is
      necessary to further elucidate the mode(s) of antidepressant action. Given what
      is currently known and unknown about the biological properties of Hypericum,
      those who choose to use this herb should be closely monitored by a physician.

PMID- 11243489
TI  - Acute dose-effects of scopolamine on false recognition.
AB  - RATIONALE: Recently, there has been increased research interest in the phenomenon
      of false recognition, in which participants claim to recognize words that had not
      been presented during an initial study phase but that are associatively related
      to presented words. Acute administration of the benzodiazepine hypnotic triazolam
      has been shown to decrease false recognition rates. However, no false recognition
      studies have examined the effects of scopolamine, an anticholinergic drug that
      might produce a different profile of memory-impairing effects than the
      benzodiazepines due to its distinct neurochemical profile. OBJECTIVE: This study
      was designed to examine the acute dose-effects of scopolamine on false
      recognition. METHODS: The effects of subcutaneously administered scopolamine (0.3
      and 0.6 mg/70 kg) on performance in the Deese/Roediger-McDermott false
      recognition paradigm were examined in a repeated-measures placebo-controlled
      double-blind design in 18 healthy volunteers. RESULTS: Scopolamine produced dose
      related reductions in both true and false recognition rates, and induced a more
      conservative response bias relative to placebo for recollection-based
      ("remember") responses to studied words. CONCLUSIONS: While scopolamine's effects
      on false recognition are similar to those observed previously with triazolam, its
      effects on response bias may differ from those of triazolam.

PMID- 11243488
TI  - GABA(B) receptors play a role in the development of tolerance to ethanol in mice.
AB  - RATIONALE: There is evidence that drugs that improve or impair learning can
      facilitate or block ethanol tolerance, respectively. Since GABA(B) receptors have
      been shown to be involved in processes related to learning, it is possible that
      this system could play a role in the development of rapid tolerance to ethanol.
      OBJECTIVES: The aim of this study was to verify the influence of one GABA(B)
      agonist and two GABA(B) antagonists on tolerance to the effect of ethanol on
      motor coordination. METHODS: Male Swiss mice were trained on a continuously
      accelerating rota-rod device. Animals were pretreated with the GABA(B) agonist (
      )-baclofen (3, 5, or 7 mg kg(-1)) or saline, 30 min before ethanol (1.75 g kg(
      1)), and were tested 5, 10, and 15 min later on the rota-rod. In another set of
      experiments, mice were pretreated with the GABA(B) antagonists CGP36742 (1, 3,
      10, or 30 mg kg(-1)) or CGP56433 (0.1, 0.3, 1.0, or 3.0 mg kg(-1)), or saline, 30
      min before the test under ethanol. Rapid tolerance was evaluated 24 h after the
      first ethanol injection, by injecting all animals with ethanol and retesting them
      on the rota-rod. RESULTS: The results showed that (-)-baclofen (5 mg kg(-1))
      significantly (ANOVA + Tukey's test) blocked rapid tolerance, whereas CGP36742 (3
      and 10 mg kg(-1)) and CGP56433 (0.3, 1, and 3 mg kg(-1)) facilitated rapid
      tolerance in a dose-dependent way. The blockade of rapid tolerance by (-)
      baclofen was antagonized by previous administration of CGP36742 or CGP56433.
      CONCLUSIONS: The current results suggest that rapid tolerance to ethanol is
      subjected to inhibition by a GABAergic GABA(B) receptor-mediated system in the
      mouse.

PMID- 11243490
TI  - Prenatal AZT or 3TC and mouse development of locomotor activity and hot-plate
      responding upon administration of the GABA(A) receptor agonist muscimol.
AB  - RATIONALE: Zidovudine (AZT) and lamivudine (3TC) are nucleoside analogues
      administered prenatally in clinical practice, separately or in combination, as
      antiretroviral drugs to prevent HIV mother-to-child transmission by inhibiting
      viral reverse transcriptase. In animal studies pre- and/or perinatal exposure to
      AZT and 3TC induce age- and sex-dependent neurobehavioural alterations in the
      offspring. OBJECTIVE: Investigation of short- and medium-term effects of in utero
      exposure to AZT or 3TC on development of the GABAergic system. METHODS: Pregnant
      CD-1 mice were given orally twice daily AZT (160 mg/kg), 3TC (500 mg/kg) or
      vehicle solution (NaCl 0.9%) from pregnancy day 10 to delivery. Offspring
      locomotion and nociceptive sensitivity were examined on postnatal day (pnd) 8,
      14, and 28 after administration of two doses of GABAergic agonist muscimol (pnd 8
      and 14: 0.05 and 0.2 mg/kg; pnd 28: 0.2 and 1.0 mg/kg). A 30-min locomotor
      activity test and a 60 s hot-plate test (50+/-1 degrees C) were used. RESULTS:
      AZT and 3TC treated mice showed a mild increase of locomotor activity after
      administration of the high dose muscimol on pnd 8. On pnd 14 the low muscimol
      dose enhanced locomotor activity in vehicle and 3TC, but not in AZT pups, whereas
      no prenatal treatment effect was evident on pnd 28. AZT increased nociceptive
      sensitivity at all ages considered. CONCLUSIONS: Prenatal AZT effects on
      locomotor activity appear clearly detectable after GABAergic challenge and seem
      to be transient. AZT effects on pain sensitivity did not appear to be dependent
      on GABA regulated nociceptive mechanisms. Prenatal 3TC exposure had rather
      limited effects on locomotor activity development, and no effect on nociception.

PMID- 11243491
TI  - Comparison of antidepressant activity in 4- and 40-week-old male mice in the
      forced swimming test: involvement of 5-HT1A and 5-HT1B receptors in old mice.
AB  - RATIONALE: A recent study suggested that selective serotonin reuptake inhibitors
      were inactive in 40-week-old male mice in the mouse forced swimming test,
      possibly because of alteration of 5-HT1 receptors. OBJECTIVES: The present study
      was aimed at investigating the action of various antidepressant drugs in 4- and
      40-week-old male mice using the mouse forced swimming test and determining the
      involvement of 5-HT1A and 5-HT1B receptors mediating the effects. METHODS:
      Different classes of antidepressants [imipramine (tricyclic), maprotiline
      (noradrenline reuptake inhibitor), venlafaxine (mixed serotonin and noradrenaline
      reuptake inhibitors), fluvoxamine and sertraline (selective serotonin reuptake
      inhibitor)] were tested in the same randomised experimental session, alone and in
      combination with 5-HT1A and 5-HT1B receptor agonists [buspirone (partial 5-HT1A
      agonist), anpirtoline (5-HT1B agonist)] in the mouse forced swimming test.
      RESULTS: All antidepressants were found to be active in the mouse forced swimming
      test in 4-week-old mice and 40-week-old mice, with the exception of fluvoxamine
      in the 40-week-old mice. The anti-immobility effect after antidepressant
      administration was higher in 4-week-old male mice than in 40-week-old male mice.
      Venlafaxine is the most active antidepressant drug in 40-week-old mice. Prior
      administration of buspirone (0.06 mg/kg, i.p.) or anpirtoline (1 mg/kg, i.p.)
      enhanced the antidepressant-like effects in 4-week-old mice (except in the case
      of sertraline, 8 mg/kg). In elderly mice, only prior administration of buspirone
      enhanced the antidepressant-like effects of fluvoxamine. A neurochemical study
      showed that significantly higher serotonin and dopamine concentrations were found
      in 40-week-old control mice brains than 4-week-old control mice brains but that
      the noradrenaline concentration is higher in 4-week-old mice. CONCLUSION:
      Tricyclic, noradrenaline reuptake inhibitors and serotonin reuptake inhibitors
      are more active in 4-week-old mice than 40-week-old mice. Our results suggested
      that 5-HT1B receptors may be more altered than 5-HT1A receptors in 40-week-old
      mice.

PMID- 11243492
TI  - Transplacental transfer of amitriptyline and nortriptyline in isolated perfused
      human placenta.
AB  - RATIONALE: Although tricyclic antidepressants (TCAs) have gained wide acceptance
      for use in the treatment of depression in pregnant women, their pharmacokinetics
      during pregnancy have been poorly characterized. The aim of the present study was
      to investigate the transplacental transfer of amitriptyline (AMI) and its main
      active metabolite nortriptyline (NOR) in isolated perfused human placenta.
      METHODS: Nine term human placentae were obtained immediately after delivery with
      maternal consent and a 2-h non-recirculating perfusion of a single placental
      cotyledon was performed. AMI (200 ng/ml) and NOR (150 ng/ml), with antipyrine as
      a reference compound, were added to the maternal reservoir and their appearance
      to the fetal circulation was followed for 2 h. AMI and NOR concentrations were
      measured by high performance liquid chromatography (HPLC) and antipyrine
      concentrations spectrophotometrically. RESULTS: The mean (SD) transplacental
      transfers (TPT(SS)%) for AMI and NOR were 8.2 (2.3)% and 6.5 (1.8)%,
      respectively, calculated as the ratio between the steady-state concentrations in
      fetal venous and maternal arterial sides. The TPTs of AMI and NOR were 81% and
      62% of the freely diffusable antipyrine. The absolute fraction of the dose that
      crossed the placenta (TPT(A)) was moderately, but significantly higher for AMI
      (7.7%) than for NOR (5.7%) (P=0.037). In all perfusions, steady state at the
      fetal side was reached by 30 min for AMI and by 50 min for NOR in the fetal side.
      The viability of the placentae was retained during the 2-h perfusion, as
      evidenced by unchanged pH of the perfusate and by stable perfusion pressures in
      fetal artery and stable antipyrine transfer. CONCLUSIONS: Both AMI and NOR cross
      the human placenta. However, the fetal exposure with NOR may be somewhat smaller
      compared with AMI, probably due to the higher lipophilicity of AMI.

PMID- 11243493
TI  - The effects of excitotoxic lesions of the nucleus accumbens core or shell regions
      on intravenous heroin self-administration in rats.
AB  - RATIONALE: It has been suggested that the nucleus accumbens (NAcc) may be
      involved in heroin reward, and the core and shell regions respond differently
      following administration of a number of drugs of abuse. OBJECTIVE: The possible
      role of the NAcc core and shell subregions in the acquisition of heroin self
      administration behaviour was investigated. METHODS: Rats were given selective
      excitotoxic lesions of either the nucleus accumbens core or shell before the
      acquisition of responding for i.v. heroin (0.04 mg/infusion) under a continuous
      reinforcement schedule in daily 3 h sessions. After sham-lesioned rats reached a
      stable baseline, a between-sessions heroin dose-response function was
      established. RESULTS: Rats with lesions of the NAcc shell did not differ
      significantly from sham controls in either the acquisition of heroin self
      administration or in their heroin dose-response function. The NAcc core lesion
      group showed reduced levels of responding during the acquisition of heroin self
      administration and a reduction in responding during the heroin dose-response
      function, although this behaviour was sensitive to changes in the dose of heroin.
      CONCLUSIONS: The NAcc shell does not appear to be critical for heroin self
      administration, whereas the NAcc core, although apparently not essential in
      mediating the rewarding effect of i.v. heroin, may mediate processes that are of
      special importance during the acquisition of instrumental behaviour.

PMID- 11243494
TI  - The effects of nucleus accumbens core and shell lesions on intravenous heroin
      self-administration and the acquisition of drug-seeking behaviour under a second
      order schedule of heroin reinforcement.
AB  - RATIONALE: Evidence has implicated the nucleus accumbens (NAcc) in drug-seeking
      and -taking behaviour. However, the importance of the "core" and "shell"
      subdivisions of the NAcc in heroin-seeking and -taking behaviour remains unclear.
      OBJECTIVES: To investigate the function of the NAcc core and shell in heroin self
      administration and heroin-seeking behaviour. METHODS: Male rats were trained to
      self-administer heroin (0.12 mg/kg per infusion) under a continuous reinforcement
      (CRF) schedule. After responding stabilised, rats were given excitotoxic (or
      sham) lesions of either the NAcc core or shell and after recovery were assessed
      for their retention of heroin self-administration under CRF. At this point a
      second-order schedule of reinforcement was introduced, commencing at FR10 (FR1:S)
      and terminating at FR10 (FR10:S), in which ten lever presses resulted in
      presentation of the heroin-associated CS+, and completion of ten such units
      resulted in drug infusion. RESULTS: Within 7 days, all groups re-acquired
      responding for heroin under CRF at rates similar to their pre-lesion performance.
      However, rats with lesions of the NAcc core, but not shell, were severely
      impaired in the acquisition of heroin-seeking behaviour. CONCLUSIONS: These
      results indicate an important role for the core of the NAcc in the acquisition of
      heroin-seeking behaviour under the control of drug-associated stimuli.

PMID- 11243495
TI  - Alcohol, allopregnanolone and aggression in mice.
AB  - RATIONALE: Aggressive behavior of certain individual animals can be greatly
      increased when under the influence of low doses of alcohol. One of alcohol's
      neurochemical actions that may be relevant to alcohol-heightened aggression (AHA)
      is its positive modulation of the GABA(A) receptor complex. OBJECTIVE: The
      objective of this study was to investigate whether alcohol interacts with an
      endogenous modulator of the GABA(A) receptor complex, the neurosteroid
      allopregnanolone, in stimulating/heightening aggressive behavior. METHODS AND
      RESULTS: The first experiment was designed to test the hypothesis that
      neurosteroid modulators of the GABA(A) receptor complex will increase aggression
      and to compare these effects with alcohol. Male CFW mice were injected with
      allopregnanolone, alphaxalone (3-30 mg/kg, i.p.), or alcohol (1.0 g/kg, p.o.) 15
      min prior to a 5-min confrontation with an intruder. Moderate doses of alcohol
      and the neurosteroids increased aggression by ca. 50% above baseline; impaired
      locomotion was seen only at the highest doses. A second experiment compared AHA
      and ANA (i.e. alcohol-non-heightened aggression) mice by giving allopregnanolone
      (1-10 mg/kg) with a simultaneous oral injection of alcohol (0.6 or 1.0 g/kg) or
      water. When administered with water and the 0.6 g/kg dose of alcohol,
      allopregnanolone increased the aggression of AHA and ANA mice. Administration of
      the 1.0 g/kg dose of alcohol in ANA mice prevented allopregnanolone-heightened
      aggression. In AHA mice, addition of allopregnanolone to 1.0 g/kg alcohol dose
      dependently reduced alcohol-heightened aggression, suggesting potentiation of
      alcohol's suppressive effects on aggression. CONCLUSIONS: The neuroactive steroid
      allopregnanolone appears to play an important role in alcohol-heightened
      aggression. Moreover, the upward shift of the aggression-heightening effects of
      alcohol and the downward shift at the maximally effective alcohol dose by
      allopregnanolone point to a shared mechanism for both positive modulators of the
      GABA(A) receptor complex.

PMID- 11243497
TI  - Extinction and spontaneous recovery of ataxic tolerance to ethanol in rats.
AB  - RATIONALE AND OBJECTIVES: Two experiments with rats using an ethanol ataxia
      method investigated extinction and spontaneous recovery of tolerance. Tolerance
      extinction has been shown with a variety of drugs and methods, but until now it
      has not been shown with ethanol ataxia. Extinction was investigated here because
      of its connection with cue exposure treatments, and also to allow an assessment
      of spontaneous recovery. Spontaneous recovery is the return of conditioned
      responses, such as those potentially contributing to tolerance, when time passes
      after extinction. In terms of response topography it resembles instances of
      relapse in humans. Its demonstration constitutes one technique for illustrating
      that the effects of extinction are often temporary. There are no published
      reports showing a recovery of tolerance to any drug due to the passage of time
      after extinction. A demonstration of spontaneous recovery contributes to an
      understanding of the effects and time course of tolerance extinction. It also
      raises the possibility that spontaneous recovery involving drug tolerance has
      mechanisms similar those involved in instances of spontaneous recovery studied
      more extensively with non-drug methods. METHODS: In one experiment, ataxic
      tolerance was conditioned to a strobelight conditioned stimulus (CS) by exposing
      rats to the strobelight while experiencing the effects of an ethanol injection.
      Tolerance was extinguished in 17 or 24 once-daily trials by presenting the
      strobelight without ethanol (with saline). The effect of those numbers of trials
      was assessed on the day after extinction in the presence of the strobelight when
      ethanol was again injected. The effect was compared to the effect of the
      strobelight and ethanol in naive rats and in rats that had received only
      tolerance conditioning. In a second experiment, ataxic tolerance was conditioned
      and then extinguished over 17 trials, just as in the other experiment. Different
      groups were then tested 1, 12, 18, and 24 days after extinction in the presence
      of the strobelight when ethanol was again injected. RESULTS: Ataxic tolerance was
      fully extinguished after either 17 or 24 trials, as shown by comparisons with the
      naive and conditioning-only controls. Tolerance was greater (it recovered) when
      the strobelight CS was reintroduced 24, 18, and even 12 days after extinction,
      compared with testing 1 day after extinction. CONCLUSIONS: Conditioned ataxic
      tolerance can be extinguished, just as other conditioned tolerances can. More
      important, the return of tolerance over time after extinction represents
      spontaneous recovery of ethanol tolerance, and indicates that as in other
      conditioning preparations, extinction does not result in unlearning of the
      original conditioning association. The identification of spontaneous recovery of
      tolerance isolates a robust source of the potential for drug use relapse: the
      mere passage of time after extinction.

PMID- 11243496
TI  - Corticosterone responses in 5-HT1B receptor knockout mice to stress or 5-HT1A
      receptor activation are normal.
AB  - RATIONALE: Previous research found no adaptations in presynaptic 5-HT1A receptors
      in mice lacking 5-HT1B receptors (5-HT1B KO). Stress and 5-HT1A receptor agonists
      induce corticosterone release in mice via hypothalamus-pituitary-adrenal (HPA)
      axis activation. 5-HT1B KO mice are hyperreactive to mild stressors and this
      might be reflected in altered postsynaptic 5-HT1A receptor sensitivity.
      OBJECTIVES: Our aim was to determine whether the activity of the HPA axis was
      increased in 5-HT1B KO mice in response to mild stress and pharmacological
      activation of 5-HT1A receptors as an indication of putative adaptive changes in
      postsynaptic 5-HT1A receptor function. METHODS: The effect of mild stress [i.e.,
      the stress-induced hyperthermia (SIH) paradigm], induced by rectal temperature
      measurement, was determined on temperature and corticosterone over time (0, 5,
      10, 20, 30, 60, and 90 min) in 5-HT1B KO and wildtype mice. In addition,
      corticosterone was measured 60 min after 5-HT1A receptor activation by flesinoxan
      (0, 0.03, 0.1, 0.3, 1, and 3 mg/kg s.c.). Blood was collected and plasma
      corticosterone levels were determined by radioimmunoassay. RESULTS: Both
      genotypes showed comparable time-dependent SIH responses, whereas basal
      temperature was higher in 5-HT1B KO mice. The effect of SIH on temperature was
      mirrored by mild increases in plasma corticosterone. Activation of 5-HT1A
      receptors caused a strong dose-dependent release of corticosterone in both
      genotypes. Neither response observed showed differences between both genotypes.
      CONCLUSIONS: Although 5-HT1B KO mice are hyperreactive to mild stress, this
      reactivity is not reflected by stronger corticosterone responses in the SIH
      paradigm. The lack of shift in dose-response curves for flesinoxan suggests that
      postsynaptic 5-HT1A receptor function is unaffected in 5-HT1B KO mice.

PMID- 11243498
TI  - Reboxetine plus citalopram for refractory depression not responding to
      venlafaxine: possible mechanisms.

PMID- 11243499
TI  - How effective is antenatal care in preventing maternal mortality and serious
      morbidity? An overview of the evidence.
AB  - This is an overview of evidence of the effectiveness of antenatal care in
      relation to maternal mortality and serious morbidity, focused in particular on
      developing countries. It concentrates on the major causes of maternal mortality,
      and traces their antecedent morbidities and risk factors in pregnancy. It also
      includes interventions aimed at preventing, detecting or treating any stage along
      this pathway during pregnancy. This is an updated and expanded version of a
      review first published by the World Health Organization (WHO) in 1992. The
      scientific evidence from randomised controlled trials and other types of
      intervention or observational study on the effectiveness of these interventions
      is reviewed critically. The sources and quality of available data, and possible
      biases in their collection or interpretation are considered. As in other areas of
      maternal health, good-quality evidence is scarce and, just as in many aspects of
      health care generally, there are interventions in current practice that have not
      been subjected to rigorous evaluation. A table of antenatal interventions of
      proven effectiveness in conditions that can lead to maternal mortality or serious
      morbidity is presented. Interventions for which there is some promising evidence,
      short of proof, of effectiveness are explored, and the outstanding questions
      formulated. These are presented in a series of tables with suggestions about the
      types of study needed to answer them.

PMID- 11243501
TI  - Desloratadine activity in concurrent seasonal allergic rhinitis and asthma.
AB  - Seasonal allergic rhinitis (SAR) and asthma, which are frequently comorbid, share
      some common allergic pathogenic bases. Clinical manifestations of these disorders
      might therefore be viewed as local manifestations of a systemic inflammatory
      state. Not only do the onsets of allergic-rhinitis (AR) and asthma symptoms often
      coincide (within 1 year), but also nasal challenges with SAR allergens can induce
      airways hyperreactivity (AHR). Eosinophils, which are key effector cells in both
      SAR and asthma, cause AHR, tissue damage, and neuronal effects through secretion
      of toxic granule proteins, enzymes, and other mediators. The novel, nonsedating,
      histamine H1-receptor antagonist, desloratadine, which exerts various favorable
      effects on the allergic cascade, significantly decreased SAR symptoms (e.g.,
      nasal congestion) and diminished daily beta2-agonist use and improved asthma
      symptoms, while maintaining pulmonary function, in patients with SAR-asthma who
      were treated with once-daily desloratadine regimens.

PMID- 11243500
TI  - Decongestant efficacy of desloratadine in patients with seasonal allergic
      rhinitis.
AB  - Recent advances in experimental immunologic approaches to seasonal allergic
      rhinitis (SAR) have led to a shift in the concepts of its pathogenesis. The
      conventional view of SAR as a local response to inhaled allergens has largely
      given way to a new view of this disorder as a systemic condition with local
      tissue manifestations. This concept, together with an increasing recognition of
      specific mediators' distinct roles in driving the early- and late-phase allergic
      responses, has opened multiple lines of therapeutic attack within the allergic
      cascade. Potent inhibition of inflammatory mediator release at distinct points in
      this cascade is conferred by desloratadine. In addition to the familiar range of
      SAR symptoms amenable to antihistamine therapy, desloratadine uniquely attenuates
      patient ratings of nasal congestion. This novel, nonsedating histamine H1
      receptor antagonist is the only once-daily antiallergic product with a consistent
      decongestant effect that begins within hours of the first morning dose and is
      sustained for the entire treatment period.

PMID- 11243503
TI  - Desloratadine: a new approach in the treatment of allergy as a systematic disease
      -pharmacology and clinical overview. Introduction.

PMID- 11243502
TI  - Desloratadine in the treatment of chronic idiopathic urticaria.
AB  - Chronic idiopathic urticaria (CIU) is a common dermatologic disorder that may
      severely impair quality of life. Patients may suffer symptoms such as pruritus
      and disfigurement due to wheals for years or decades. Advances have been made in
      the last 10 years with the identification of an autoimmune pathogenesis in a
      significant proportion of patients. Despite this, treatment remains symptomatic,
      and antihistamines are the first choice of therapy once the diagnosis of CIU has
      been established. The goal of treatment is rapid, long-lasting symptom relief,
      and currently available antihistamines fail to provide this in many cases.
      Desloratadine is a novel, potent H1-receptor antagonist with additional
      inhibitory effects on inflammatory mediators such as cytokines and adhesion
      molecules. Newly published data on the efficacy and safety of desloratadine in
      CIU is highly encouraging, suggesting that the drug may improve symptom control
      above that currently available.

PMID- 11243505
TI  - CD40 ligand--an important target for immunotherapy?

PMID- 11243506
TI  - Suppression of experimental systemic lupus erythematosus (SLE) in mice via TNF
      inhibition by an anti-TNFalpha monoclonal antibody and by pentoxiphylline.
AB  - We have previously shown that the clinical manifestations of experimental
      systemic lupus erythematosus (SLE) correlate with an early increased secretion of
      TNFalpha and IL-1. In the present study, we examined the efficacy of two
      therapeutic modalities which lower TNFalpha production or activity, on the
      clinical manifestations of the disease. Experimental SLE was induced in naive
      C3H.SW mice by injection of the human anti-DNA monoclonal antibody (mAb) bearing
      the common idiotype, 16/6 Id. Two weeks after booster injections, treatment with
      either an anti-TNFalpha mAb, or pentoxiphylline (PTX) was started, for a period
      of 6 weeks. Production of TNFalpha (by splenocytes) and IL-1 (by peritoneal
      macrophages) was determined 3 and 7 months after disease induction. The
      experimental mice were also followed for disease manifestations. Both treatment
      protocols, with anti-TNFalpha mAb and with PTX, reduced the production of the two
      pro-inflammatory cytokines. TNFalpha and IL-1, in mice with experimental SLE.
      Anti-DNA antibodies were significantly lower in the mice treated with either
      protocol. In addition, a significantly lower rate of leukopenia, proteinuria and
      immune complex deposition was observed in treated mice. Abrogation of TNFalpha
      and IL-1 production in the early stages of experimental SLE by an anti-TNFalpha
      mAb or by PTX improves the clinical status of mice afflicted with this autoimmune
      disease.

PMID- 11243504
TI  - The pharmacologic profile of desloratadine: a review.
AB  - Desloratadine is a new agent for the treatment of diseases such as seasonal
      allergic rhinitis and chronic urticaria. The pharmacologic profile of
      desloratadine offers particular benefits in terms of histamine H1-receptor
      binding potency and H1 selectivity. Desloratadine has a half-life of 21-24 h,
      permitting once-daily dosing. No specific cautions are required with respect to
      administration in renal or hepatic failure, and food or grapefruit juice have no
      effect on the pharmacologic parameters. No clinically relevant racial or sex
      variations in the disposition of desloratadine have been noted. In combination
      with the cytochrome P450 inhibitors, ketoconazole and erythromycin, the AUC and
      Cmax of desloratadine were increased to a small extent, but no clinically
      relevant drug accumulation occurred. With high-dose treatment (45 mg/day for 10
      days), no significant adverse events were observed, despite the sustained
      elevation of plasma desloratadine levels. Specifically, desloratadine had no
      effects on the corrected QT interval (QTc) when administered alone, at high dose,
      or in combination with ketoconazole or erythromycin. Preclinical studies also
      show that desloratadine does not interfere with HERG channels or cardiac
      conduction parameters even at high dose. Desloratadine is nonsedating and free of
      antimuscarinic/anticholinergic effects in preclinical and clinical studies. Novel
      antiallergic and anti-inflammatory effects have also been noted with
      desloratadine, a fact which may be relevant to its clinical efficacy.

PMID- 11243507
TI  - Echocardiography and pulmonary function testing in childhood onset systemic lupus
      erythematosus.
AB  - The aim of this paper was to investigate the frequency of echocardiography (ECHO)
      and pulmonary function test (PFT) abnormalities in childhood onset systemic lupus
      erythematosus (SLE), and to determine the relationship of these abnormalities to
      disease activity. The charts of 50 patients with childhood onset SLE attending a
      pediatric rheumatology clinic were reviewed for ECHO and PFT studies. The
      frequency and description of ECHO and PFT abnormalities were documented. Possible
      associations of PFT and ECHO abnormalities with clinical cardiopulmonary disease,
      radiographic findings, and measures of lupus disease activity were evaluated.
      Forty patients (80%) had at least one ECHO study. Twenty-seven (68%) had an
      abnormal initial study. Nine of 14 patients with an initial abnormal ECHO had
      normal findings on repeated study. Three abnormalities were considered moderately
      severe. Thirty-three patients (66%) had at least one PFT performed. Sixteen (48%)
      were abnormal initially. Four of these 'abnormal' studies were repeated and the
      abnormalities persisted. Nine patients (27%) were considered to have a severe
      abnormality. Thirty-one children (62%) had both studies performed. An initial
      abnormal ECHO and abnormal PFT was found in 10 (32%) of these children. No
      relationship between ECHO or PFT abnormality and any measure of disease activity
      (physician's global assessment, anti DNA, C3 or ESR) could be found. Occult
      cardiac and pulmonary disease as demonstrated by ECHO or PFT occurs frequently in
      childhood onset SLE. If we wish to understand the natural history of these
      abnormal heart and lung findings, it will be necessary to do serial testing with
      ECHO and PFTs in this population.

PMID- 11243508
TI  - Lupus in the family--analysis of a cohort followed from 1978 to 1999.
AB  - Familial lupus is recognised but rarely described in mother-daughter case pairs.
      We describe the prevalence of lupus occurring in the first degree relatives of a
      cohort of 300 lupus patients under long-term follow-up at a specialised lupus
      clinic. Three instances of mothers and their daughters who both developed the
      disease are described in detail to try and ascertain whether there are any
      particular clinical/serological/genetic factors in common which might explain the
      phenomenon.

PMID- 11243509
TI  - Anti-cardiolipin and anti-beta2 glycoprotein I antibodies in Indian patients with
      systemic lupus erythematosus: association with the presence of seizures.
AB  - The aim of this study was to examine whether the clinical features of
      antiphospholipid antibody syndrome are associated with anti-cardiolipin and anti
      beta2 glycoprotein I antibodies in Indian patients with SLE. Seventy-six patients
      (71 females), who fulfilled 1982 ACR criteria for SLE, were prospectively studied
      for the clinical features of antiphospholipid antibody syndrome (APS), and their
      sera were analysed for the presence of IgG/IgM/IgA anti-cardiolipin antibodies
      (aCL) by an in-house ELISA and, in 65 of them, for the presence of IgG anti-beta2
      glycoprotein I antibodies (anti-beta2 GPI) by a commercial kit. Thirty-nine (51%)
      patients were positive for aCL, all of which were positive for IgG aCL, either
      alone (79.6%) or along with IgM and/or IgA. Twenty-seven (69.3%) out of 39 aCL
      positive and seven (26.9%) out of 26 aCL-negative sera were positive for IgG
      antibodies to beta2 GPI. There was a significant correlation (r = 0.66, P < 0.05)
      between the levels of aCL and anti-beta2 GPI antibodies. Forty-one patients had
      features of definite or suggestive APS. Thrombocytopenia, recurrent pregnancy
      loss and CNS manifestations (seizures eight, infarct one) were seen in 20, 13 and
      nine patients, respectively. Thrombosis of the peripheral vessels was seen in
      only one patient. Only the presence of seizures was significantly associated with
      the presence of aCL and anti-beta2 GPI antibodies (P < 0.05). The characteristic
      association of definite APS (recurrent pregnancy loss and arterial/venous
      thrombosis) was lacking.

PMID- 11243510
TI  - Systemic lupus erythematosus. Disease outcome in patients with a disease duration
      of at least 10 years: second evaluation.
AB  - Data related to the disease course of patients with systemic lupus erythematosus
      (SLE) with special attention to the persistence of disease activity in the long
      term are scarce. At this moment reliable figures are only known about the
      survival rate as a measure of outcome. The aim of this multicenter study was to
      describe the outcome of SLE patients with a disease duration of greater than 10
      y. Outcome parameters were two disease activity-scoring systems (SLEDAI and
      ECLAM), the end organ damage (SLICC/ACR damage index) and treatment. Our results
      are derived from 187 SLE patients followed at 10 different centres in Europe over
      a period of 1 y. Serious clinical signs or exacerbations, defined by the
      occurrence or detoriation of already existing symptoms of renal and cerebral
      nervous systems were observed in 2-11% of the patients, seizures and psychosis in
      3%, proteinuria in 11% and an increase in serum creatinine in 5% of the patients.
      No change took place in the overall damage index. Yet, the disease course in most
      patients was characterized by periods of tiredness (42-60%), arthritis (20-25%),
      skin involvement such as malar rash (32-40%), migraine (15-20%), anaemia (15%)
      and leucopenia (17-19%). Summarizing these results it is shown that patients,
      still under care after such a long time of having this disease, do have a disease
      that is far from extinguished.

PMID- 11243511
TI  - Complete heart block in an adult with systemic lupus erythematosus and recent
      onset of hydroxychloroquine therapy.
AB  - Complete heart block (CHB) is a rare complication of systemic lupus erythematosus
      (SLE), mainly seen during an acute flare-up of the disease or after high-dose
      long-term treatment with antimalarial drugs, although anti-Ro and anti-RNP
      antibodies have also been implied by some authors. A 40-y-old woman developed CHB
      in the context of an acute flare-up of SLE, first diagnosed three years ago,
      having recently commenced hydroxychloroquine (HCQ) treatment. Anti-Ro and anti
      RNP antibodies were also positive. No features of myocarditis were found. A
      temporary pacemaker was required and complete resolution was achieved on steroid
      therapy with withdrawal of antimalarial therapy. The characteristics of previous
      cases are well publicised and discussion focuses on the possible aetiology and
      pathogenesis of the present case.

PMID- 11243512
TI  - Induction of anti-DNA antibodies: commentary on article by Satake et al.

PMID- 11243513
TI  - Long-term anti-CD154 dosing in nephritic mice is required to maintain survival
      and inhibit mediators of renal fibrosis.
AB  - The CD154/CD40 pathway is required for the development and progression of disease
      in a variety of autoimmune model systems. We have demonstrated previously that
      long-term anti-CD154 treatment of nephritic (SWRxNZB)F1 mice prolonged survival
      and preserved kidney function. Herein we ask if long-term treatment is required
      and further characterize the protective effect on renal pathology by examining
      alpha-smooth muscle actin, collagen and TGF-beta1 expression in renal tissue. The
      effects of anti-CD154 on brain and heart inflammation are also examined. Three
      dosing strategies of anti-CD154 mAb were compared in SNF1 mice that exhibited
      moderate or severe nephritis: (1) weekly for 6 weeks; (2) monthly; (3) weekly for
      6-12 weeks followed by monthly dosing. Proteinuria, serum anti-DNA, anti-CD154
      pharmacokinetics and serum soluble CD154 analyses were performed. Anti-CD154
      treatment of moderate disease increased survival across all regimens, although
      weekly followed by monthly maintenance dosing proved most efficacious. This
      regime also inhibited renal alpha-smooth muscle actin and collagen deposition.
      Only the most aggressive anti-CD154 treatment protocol increased survival in
      severely nephritic mice. Long-term anti-CD154 treatment significantly inhibits
      key mediators of kidney fibrosis and is required to maximize survival and renal
      function. Potential reasons for differential therapeutic efficacy in moderately
      vs severely nephritic mice are discussed.

PMID- 11243514
TI  - Complete arterial coronary artery bypass grafting versus conventional
      revascularization--early results.
AB  - BACKGROUND: Complete arterial coronary artery bypass grafting (CABG) offers the
      potential to improve long-term results. However, an increased perioperative risk
      has been controversially discussed. New operative techniques (skeletonization of
      the ITA/ T-grafts/utilization of the radial artery (RA)) may decrease
      perioperative risk. We compared the outcome after conventional with that after
      complete arterial CABG. MATERIAL AND METHODS: Three consecutive groups of
      patients were analyzed. In group I (n = 50), CABG was performed using left ITA
      and vein grafts. The other two groups received complete arterial CABG with either
      both ITA's (group II; n = 52) or left ITA and RA (group III; n = 52). RESULTS: A
      mean of 3.9+/-0.8 (I) versus 4.2+/-0.8 (II) and 3.9+/-0.9 (III) anastomoses were
      performed per patient (ns). Mean operating time was significantly prolonged in
      group II (II: 252+/-54; p<0.0001; vs. I: 191+/-36; III: 203+/-33). Mean ischemic
      time was significantly prolonged in group II and III (II:65+/-20; p<0.0001; III:
      68+/-16; p<0.0001; vs. I: 51+/-15). Mean bypass time (I: 83+/-23; II: 95+/-41;
      III: 91+/-21), the rate of postoperative complications and in-hospital mortality
      (I: n = 0; II: n = 2; III: n = 0; ns) showed no significant differences.
      CONCLUSIONS: Complete arterial CABG using modern surgical techniques is as safe
      as the conventional surgical approach using left ITA and vein graft.

PMID- 11243515
TI  - End of the millenium--end of the single thoracic artery graft? Two thoracic
      arteries--standard for the next millenium? Early clinical results and analysis of
      risk factors in 1,487 patients with bilateral internal thoracic artery grafts.
AB  - PURPOSE: CABG with bilateral IMA grafts (BIMA) can improve long-term results in
      cardiac morbidity and mortality. An enhanced incidence of bleeding and wound
      complications compared to patients with single IMA (SIMA) remains a matter of
      debate. The aim of the study was to compare the operative outcomes of patients
      who had undergone CABG with BIMA and SIMA in situ grafts, especially to identify
      patient-related risk factors, such as obesity, diabetes mellitus and age above 70
      years. METHODS: Out of a total of 5,144 patients operated on between January 1996
      and September 1999, patients with isolated CABG (n = 3,671) with BIMA or SIMA
      were analyzed retrospectively. In the BIMA group, the patients' (n = 1,487) mean
      age was 64.0 years; mean EF was 62.1%. In the SIMA group (n = 2,184), the mean
      age was 65.4 years and mean EF 60.6% (n. s.). In the BIMA group, the right IMA
      was anterior of the aorta to the LAD, the left IMA to the lateral wall. In the
      SIMA group, the LAD was revascularisized with the left IMA. Additional bypasses
      were performed with vein grafts. RESULTS: The 30-day lethality was 1.6% in the
      BIMA group, 1.7% in the SIMA group in patients under 70, and 4.1% (BIMA) and 4.0%
      (SIMA) in patients over 70 (p = n.s.). A significantly higher blood loss was
      observed in the BIMA group (BIMA 979+/-708 ml, SIMA 790+/-575 ml, p<0.05). The
      rethoracotomy rate due to bleeding was significantly higher in patients with BIMA
      (4.1%) compared to those with SIMA (2.5%, p<0.05). In patients with a body mass
      index (BMI) of less than 27, no significant difference could be found (SIMA 2.8%,
      BIMA 3.4%, p = n. s.). Patients with a BMI >27 showed a significantly higher
      rethoracotomy rate (SIMA 2.2%, BIMA 4.9%). A higher incidence of sternal
      instabilities could be observed in the BIMA group (4.2%, p<0.05). Diabetes
      mellitus could not be identified as an independent risk factor for sternal
      complications (SIMA 2.9%, BIMA 5.0%, p = n. s.). COUCLUSION: CABG using both
      IMA's can be performed in nearly all patients as a routine method with good
      clinical results and low mortality. Bleeding in the BIMA group within 48 hours
      was increased. BMI >27 could be identified as a risk factor for sternal
      complications, but not diabetes mellitus or age over 70 years.

PMID- 11243516
TI  - Endovascular stent-graft repair of acute thoracic aortic dissection--early
      clinical experiences.
AB  - BACKGROUND: Standard treatment of acute thoracic aortic dissection type B is the
      medical therapy used for most patients, according to Stanford. Surgical therapy
      involves a high mortality rate and is reserved for patients with complicated
      dissections. We report from four patients with acute thoracic aortic dissection,
      treated endoluminally by stent-graft implantation. METHODS: Four patients with
      complicated acute thoracic aortic dissections type B were treated endoluminally
      by transfemoral stent-graft implantation. Preoperative evaluation was performed
      with spiral-computed tomography and calibrated aortography. The Talent stent
      graft system (Metronic) was used in all patients. RESULTS: The primary entry tear
      could be sealed successfully and complete thrombosis of the false thoracic aortic
      lumen was obtained in all cases. In one patient, transposition of the left
      subclavian artery was performed, in two patients the stent-grafts had to be
      placed across the origin of the left subclavian artery. No severe intra- or
      postoperative complications occurred. CONCLUSION: Endoluminal treatment of acute
      thoracic aortic dissection seems to be a less invasive and effective therapy.
      Long-term results for this method are necessary.

PMID- 11243517
TI  - Grown-up congenital heart disease--medical demands look back, look forward 2000.
AB  - A new medical community, the grown-up congenital heart patients--GUCH--has
      resulted from successes of cardiac surgery over 30-40 years. Many survivors have
      complicated problems, medical and surgical, demanding experience and expertise
      neither provided nor organised in most countries. Islands of good care exist with
      difficulty. The experience of one specialist GUCH unit established for 25 years
      shows that 55-60% admissions are for complex lesions, particularly after
      complicated surgery. The patients' overall costs are at least twice those of
      other cardiac patients. GUCH admissions are about 5-8% of the total, varying
      according to the population/region served. Supervised medical care for GUCH is
      equally important in outpatient services, involving 3 times the secretarial time
      of other cardiac patients, an accessible database and a "helpline" for doctors
      and patients. This may be life-saving in patients with complex conditions. The
      GUCH population is ageing, with increasing numbers of complex patients. 30% of
      admissions now are over 40 years old, and 5% are over 60, confirming that this is
      an adult medical speciality, not paediatric. Invasive investigations and
      arrhythmias provide the most frequent reasons for admissions--atrial flutter is
      the commonest arrhythmia, needing experts when it occurs in Fontan,
      transposition, etc. Routine coronary arteriography is also important. In cardiac
      surgery, one in five admissions presents organisational problems. Reoperation,
      now as many as 9 or 10 times, has to be optimised. Reoperation on left and right
      outflow tracts-for changing valves and conduits--is more common than first
      operations. GUCH patients represent a relatively small portion of the whole
      population. Such patients in a population of 7-8 million need to be concentrated
      in 1-2 centres, depending on culture, religion, geography, language etc., to
      provide necessary experience, expertise and education.

PMID- 11243518
TI  - Fontan completion: intracardiac tunnel or extracardiac conduit?
AB  - The concept of Fontan circulation was first clinically introduced in 1971. Since
      that time, many technical modifications have been advocated. Among them, the
      concept of total cavopulmonary connection, introduced in the late 80's, has
      experienced widespread use over the past 10 years. In this procedure, a
      bidirectional superior cavopulmonary anastomosis is performed while the inferior
      caval blood flow is directed towards the pulmonary arteries through an
      intraatrial composite tunnel. More recently, an extracardiac conduit to divert
      inferior vena cava flow to the pulmonary arteries has been advocated. The
      respective merits of these two approaches remain to be determined.

PMID- 11243519
TI  - Care of adults with congenital heart disease--a challenge for the new millennium.
AB  - The care of complex congenital heart defect (CHD) patients should be continuous
      through life. Medium- and high-risk patients should be seen in special facilities
      for grown-up congenital heart (GUCH) patients, and followed for life. CHD in the
      adult is different than CHD in the child. Transitional programs should be
      available to prepare the adolescent patient to take charge of his/her own health.
      The patient should be transferred smoothly from pediatric to adult care. GUCH
      care should be regionally anchored in special facilities (groups or sometimes
      individuals) willing to make a commitment to their care. Ideally, pediatric and
      adult cardiologists will collaborate. GUCH care should be multidisciplinary
      wherever possible--and certainly in supraregional centers. Surgery, diagnostic
      catheterization, interventional cath procedures, EP management, and even MRI
      should be done in selected centers with high quality services for all cases other
      than the most simple lesions. Care should be available at all times. Surgeons who
      operate on children with similar conditions should perform the most GUCH surgery.
      GUCH surgery should be performed in centers with adequate institutional and
      individual surgeon's volumes. In determining which surgeons and units have
      adequate volumes, both pediatric and adult volumes should be combined.

PMID- 11243520
TI  - The effect of cardiopulmonary lymphatic obstruction on heart and lung function.
AB  - Many thoracic surgical procedures involve excision or destruction of
      intrathoracic and mediastinal lymphatics. It is widely assumed that the
      mediastinal lymphatic system is surgically expendable, and that destruction of
      mediastinal lymphatics has no significant adverse physiological effect. Cardiac
      lymphatic obstruction may give rise to cardiac lymphedema and impaired cardiac
      function. Similarly, obstruction of pulmonary lymphatics may result in pulmonary
      perivascular lymphedema, endothelial injury, and pulmonary artery hypertension.
      This review summarizes the possible deleterious effects of intrathoracic
      lymphatic destruction and the benefits of pharmacological and surgical
      enhancement of active lymph drainage.

PMID- 11243521
TI  - Correction of anterior thoracic wall deformities: improved planning by means of
      3D-spiral-computed tomography.
AB  - Surgical correction of anterior thoracic wall deformities is an extensive
      procedure with considerable operative trauma. The procedure can be markedly
      supported by means of preoperative 3D spiral-computed tomography for the purpose
      of improved preoperative planning in order to avoid unnecessary tissue
      mobilization. It is also helpful to enhance the patients' comprehension regarding
      the operative requirements.

PMID- 11243522
TI  - Does the time of resternotomy for bleeding have any influence on the incidence of
      sternal infections, septic courses or further complications?
AB  - BACKGROUND: Former studies on sternal wound infections indicate predisposing
      factors like diabetes, obesity, use of bilateral internal mammary grafts,
      impaired renal function and reoperation. We wanted to evaluate whether the time
      of resternotomy for postoperative bleeding has any influence on the development
      of a sternal wound infection and other complications. METHODS: In our department,
      12,315 patients underwent median sternotomy for cardiac surgery between 1987 and
      1998. We analyzed the clinical data of all patients which were reoperated on for
      postoperative bleeding, especially patients with subsequent operations caused by
      sternal wound infections. All data were compared by T-test respectively chi2
      test, and p<0.05 was regarded as significant. RESULTS: 406 of the 12,315 patients
      were re-explored because of postoperative bleeding (3.3%). 57 (14%) of these
      patients died in the postoperative period of non-infectious complications. The
      remaining patients were divided into two groups: Group A (286 patients) (70.4%)
      did not suffer from any sternal wound complications, where as group B patients (n
      = 63) (15.6%) needed subsequent surgery due to sternal infection. There were no
      significant differences in either concerning age, clinical data and first
      operation. All patients had an average blood loss of 223 ml/hr. The time before
      re-operation for bleeding was 5.3+/-1.7 hours in group A compared to 11.1+/-4.2
      hours in group B (p<0.05). A significant delay of reoperation for bleeding could
      also be found for patients with postoperative septic complications (o: 5.2+/-1.9
      hours, +: 12.9+/-5.2 hours), renal failure, mechanical ventilation >48 hours and
      a stay in hospital >20 days. CONCLUSIONS: Early reoperation for postoperative
      bleeding decreases the number of subsequent complications, e.g. sternal wound
      infections, septic complications and prolonged mechanical ventilation.

PMID- 11243523
TI  - Inhaled nitric oxide for pulmonary hemorrhage due to acute pulmonary vein trauma.
AB  - A 57-year-old man with a history of prosthetic aortic valve and supracoronary
      ascending aortic replacement presented with a 9.8 cm Sinuses of Valsalvae
      aneurysm ruptured into the left upper pulmonary vein leading to massive pulmonary
      hemorrhage due to acute rupture of small pulmonary veins. Prosthetic graft
      replacement of the aneurysm and reconstruction of the atrial roof and left upper
      pulmonary vein was performed. Inhaled nitric oxide reversed treatment-refractory
      hypoxemia following massive small pulmonary vein trauma.

PMID- 11243524
TI  - Complete arterial revascularization in the diabetic patient--early postoperative
      results.
AB  - BACKGROUND: The prognostic benefit of arterial grafts appears to be particularly
      high in patients with diabetes mellitus, but has been limited by availability of
      grafts and sternal complications. Complete arterial coronary artery bypass
      grafting (caCABG) using skeletonized grafts, radial arteries (RA) and the T-graft
      approach may reduce the perioperative risk particularly in the diabetic patient.
      METHODS: The perioperative data of 174 diabetic (group I) and 402 non-diabetic
      patients (group II) who underwent caCABG were studied retrospectively. The
      operations were performed using bilateral internal thoracic arteries (ITA) (I:
      20%; II: 21%; ns) or ITA and RA (I: 80%; II: 79%; ns). Diabetic patients
      presented with a higher incidence of 3-vessel disease (I: 93%; II: 83%; p<0.05)
      and a lower left ventricular ejection fraction (I: 55+/-16%; 11:60+/-16%;
      p<0.05). RESULTS: No differences were found regarding need of intraaortic balloon
      pump (I: 1.7%; II: 2.7%; ns), incidence of myocardial infarction (I: 1.2%; II:
      1.7%; ns) and sternal complications (I: 2.3%; II: 1.0%; ns). In-hospital
      mortality was 1.7%(I) versus 2.2% (II) (p = ns). CONCLUSIONS: Using skeletonized
      arterial grafts and the T-graft approach, caCABG in diabetic patients is as safe
      as in non-diabetics. With the RA as a second graft, bilateral ITA harvesting is
      avoidable.

PMID- 11243525
TI  - Pseudoaneurysm complicating homograft aortic valve replacement--two different-
      courses and strategies.
AB  - The courses of two patients with pseudoaneurysm formation following aortic valve
      replacement using homografts are reported. Both patients had aortic valve
      replacement due to acute infective endocarditis with paravalvular abscess
      formation. The first case had an uneventful postoperative course; but on routine
      echocardiography, a pseudoaneurysm located at the left coronary commissure was
      found at one year follow-up. As the pseudoaneurysm was completely asymptomatic,
      the patient was followed up carefully at six months intervals. The second patient
      also had pseudoaneurysm formation postoperatively, but he presented one year
      after surgery with fever and elevated leucocyte count. He had surgical revision
      of the pseudoaneurysm because no other reason for an infection could be found.
      Four months later he presented again with infection signs and pseudoaneurysm
      formation. This time, the homograft was completely excised and another homograft
      was implanted. One year after the final operation, he is now free from re
      infection. The two presented courses show that pseudoaneurysms complicating
      aortic valve replacement should be managed according to attendant circumstances
      and symptoms.

PMID- 11243526
TI  - Acute aortic dissection during pregnancy.
AB  - We review the cases of two women with acute aortic dissection during their last
      trimester of pregnancy who underwent aortic root replacement. One patient with
      type A dissection had to undergo surgical intervention immediately, and required
      extracorporal membrane oxygenation for four days. The other patient with a pre
      diagnosed Marfan's disease had suffered a type B dissection and had to undergo
      emergency operation after developing a type A dissection nine days later.

PMID- 11243527
TI  - Primary sternal tuberculosis: a rare unhealed case treated by resection and local
      rotational flap.
AB  - Primary sternal tuberculosis is very rare. Only few cases have been reported in
      the English-language literature. We present a case of primary sternal
      tuberculosis that had intractable drainage for 18 months. Diagnosis was confirmed
      with biopsy, and there were no other tuberculous foci. No improvement was
      achieved in the status of the wound despite 4 months of chemotherapy. We applied
      the principles as in bacterial osteomyelitis of sternum, resected the wound and
      covered it with a pectoralis major musculocutaneous rotational flap. The wound
      healed, and there was no recurrence 24 months after surgery.

PMID- 11243528
TI  - Medical liability disputes involving thoracic and cardiovascular surgeons.
AB  - BACKGROUND: Medical malpractice claims against surgeons are increasing. In
      Germany, as in most other European countries, there is no central registry of
      medical malpractice claims. It is not known at which rate medical liability
      claims are decided in favor of the physician or the patient. METHODS: All cases
      of reproaches of medical malpractice in which our clinic was involved within the
      10-year period between 1989 to 1999 were reviewed. To compare our results with
      the general experience in the field of thoracic and cardiovascular surgery, we
      reviewed the data of the regional medical society in the same time period.
      RESULTS: From 1989 to 1999, our Clinic was involved in 74 medical liability
      disputes. There were 28 reproaches of medical malpractice against our department
      (0.1% of cases performed). Malpractice was detected in only 7 of 74 claims
      (9.5%). Most reproaches were made for incorrectly performed operations (80%), but
      only 4 (6.8%) of 59 claims were regarded as medical malpractice. CONCLUSIONS:
      Reliable data on reproaches of medical malpractice are virtually absent. Only 10%
      of all reproaches in our study were finally regarded as medical malpractice. A
      central registry of medical malpractice cases would allow analysis of the areas
      in which we have to improve performance, and how unjustified reproaches of
      medical malpractice can be avoided.

PMID- 11243529
TI  - Identification of early predictors for post-traumatic pneumonia.
AB  - We demonstrated that the standard clinical criteria of fever, leukocytosis,
      purulent sputum, and infiltrate on chest radiograph are nonspecific for the
      diagnosis of post-traumatic pneumonia, and only approximately 50 per cent of
      patients with these conditions have pneumonia. Quantitative cultures of
      bronchoalveolar lavage effluent will differentiate pneumonia (requiring
      antibiotic therapy) from systemic inflammatory response syndrome (not requiring
      antibiotics). Early identification of patients at risk for pneumonia can target
      populations for clinical research. Because risk factors for pneumonia when
      diagnosed by quantitative cultures have not been defined we reviewed our recent
      experience to identify variables predictive of pneumonia. Patients over a 22
      month period who survived > 48 hours were identified from the trauma registry.
      Pneumonia was defined as growth of > or = 10(5) organisms per milliliter in the
      bronchoalveolar lavage effluent. Risk factors evaluated included injury severity
      and severity of shock. There were 7503 patients (75% with blunt and 25% with
      penetrating injuries). The incidence of pneumonia was 6 per cent (7% of patients
      with blunt and 2% of patients with penetrating injuries). Logistic regression
      analysis identified age; Glasgow Coma Scale score; Injury Severity Score;
      transfusion requirements during resuscitation; spinal cord injury; chest injury
      severity; and emergent femur fixation, craniotomy, and laparotomy as being
      independent predictors of pneumonia. We conclude that multiple risk factors,
      which are all able to be determined early after injury, are predictive of post
      traumatic pneumonia. Prompt identification of this high-risk group of patients
      allows prognostic considerations relative to patient management schemes and
      targets populations for prophylactic measures or immunomodulation.

PMID- 11243530
TI  - Metastatic soft tissue squamous cell carcinoma.
AB  - Metastatic squamous cell carcinoma of the soft tissue is extremely rare. We
      report two patients with soft tissue metastasis from squamous cell carcinoma of
      the cervix in one and scalp in another. Case 1: A 63-year-old black woman with a
      history of cervical cancer presented with a painful mass over the right scapula.
      An incisional biopsy revealed squamous cell carcinoma. She underwent radiation
      treatment followed by wide local excision with en bloc resection and a
      myocutaneous flap closure. Case 2: A 46-year-old white man with a history of
      squamous cell carcinoma of the scalp and two kidney transplantations requiring
      long-term immunosuppression presented with a 2-month history of a left proximal
      arm mass. Magnetic resonance imaging revealed that the mass was within the
      triceps muscle and fixed to the humerus. Biopsy revealed squamous cell carcinoma.
      He underwent a shoulder disarticulation for tumor invasion into the adjacent
      humerus and neurovascular bundles. The patients remain disease-free at 12 and 8
      months, respectively. To our knowledge there are no reports of soft tissue
      squamous cell carcinoma metastatic from the cervix and only rare cases from the
      lung, head, and neck. The optimal mode of treatment and prognosis is undefined in
      these patients because of its rare incidence. Surgery and radiation with curative
      intent were used.

PMID- 11243531
TI  - Prospective comparison between laparoscopic preperitoneal herniorrhaphy and open
      mesh herniorrhaphy.
AB  - Controversy persists regarding the most effective inguinal hernia repair. The
      purpose of this study is to compare the complications, charges, patient
      satisfaction, and recovery time between laparoscopic (LH) and open mesh
      herniorrhaphy (OH). A nonrandomized prospective analysis of 233 consecutive
      inguinal hernia repairs was performed over a 12-month period by 27 surgeons. The
      type of repair was determined by surgeon preference. Cost analysis was performed
      using anesthesia records and hospital cost. Patient satisfaction and recovery
      time were evaluated by third-party interview. A total of 113 OHs and 120 LHs were
      performed; 11 OHs and 42 LHs were bilateral. Patient demographics were equivalent
      for the two groups. No statistical difference was noted when comparing
      anesthesia/operating room time between the two groups. The LHs accrued an
      additional charge of $2254 per case. Complication rates were 4.4 per cent for the
      OHs and 8.3 per cent for the LHs. All complications were considered minor. No
      infectious complications or recurrences were noted in either group. Satisfaction
      rates and pain indices were nearly identical for both OHs and LHs. The LHs had a
      shorter recovery time by 5.5 days. We conclude that LH is associated with a
      higher complication rate and cost than OH. Pain indices are similar, but LH has a
      shorter recovery time.

PMID- 11243532
TI  - Vagus nerve stimulation in pediatric patients with intractable epilepsy: case
      series and operative technique.
AB  - Patients with epilepsy refractory to medical therapy or who experience
      intolerable side effects from the medication may benefit from placement and
      activation of a vagus nerve stimulator (VNS) (Cyberonics, Houston, TX). We
      present our experience with the VNS implanted by a pediatric surgeon and its
      activation managed by a pediatric neurologist. Six patients (one male and five
      females) with average age 11 years, 10 months (range 7 years, 4 months to 18
      years, 1 month) received VNS implants at a community-based teaching hospital. One
      patient developed a self-inflicted wound complication secondary to persistent
      trauma at the implant site that led to removal of the implant. Before VNS
      implantation the frequency of seizures among the remaining five patients averaged
      73 per patient per month (range 20-165). Length of follow-up averaged 6.5 months
      (range 1.5-11 months). At most recent follow-up seizure frequency averaged 14 per
      month (range 1-42); this represents an average reduction of 78 per cent (range 30
      99%). We conclude that a pediatric surgeon with pediatric neurologic support can
      safely and effectively perform the VNS implantation at a hospital equipped to
      administer anesthesia to pediatric patients.

PMID- 11243533
TI  - The impact of liver dysfunction on outcome in patients with multiple injuries.
AB  - Multiple organ dysfunction syndrome (MODS) is the leading cause of late deaths
      after traumatic injury. The relative importance of dysfunction of individual
      organ systems in determining outcome from MODS has not been clearly defined. Some
      studies have suggested that hepatic dysfunction associated with MODS increases
      mortality, whereas others have suggested that it contributes little to outcome in
      trauma patients. To clarify the role of the hepatic dysfunction after traumatic
      injury we retrospectively reviewed all trauma patients with an Injury Severity
      Score > or = 14 admitted from January 1, 1994 through June 30, 1997 for the
      presence of hepatic dysfunction defined as a serum bilirubin > or = 2.0 mg/dL. Of
      the 1962 patients who met the entry criteria 154 developed hepatic dysfunction
      during their hospital stay. Patients with hepatic dysfunction were older (46 +/-
      2 versus 41 +/- 1 years), were more severely injured (Injury Severity Score 31.5
      +/- 0.9 versus 23.3 + 0.2), and had a lower prehospital blood pressure (102 +/- 3
      versus 117 +/- 1 mm Hg) compared with patients who did not develop hepatic
      dysfunction. Patients with hepatic dysfunction were more likely to present with
      shock as reflected in a lower initial emergency room blood pressure (109 +/- 3
      versus 128 +/- 1 mm Hg) and base deficit (-6.9 +/- 0.6 versus -3.5 +/- 0.1
      mEq/L). Patients who developed hyperbilirubinemia had longer lengths of stay in
      the intensive care unit (15.8 +/- 1.2 versus 3.4 +/- 0.2 days) and the hospital
      (27.4 +/- 1.7 versus 11.1 +/- 0.2 days) and a higher in-hospital mortality (16.2%
      versus 2.5%). These data demonstrate that the development of hepatic dysfunction
      reflects the severity of injury and is associated with a significantly worse
      outcome after traumatic injury.

PMID- 11243534
TI  - Follow-up abdominal computed tomography after splenic trauma in children may not
      be necessary.
AB  - Nonoperative management of splenic injuries in children is well accepted.
      However, the need for follow-up abdominal CT to document splenic healing has not
      been well studied. We retrospectively reviewed initial and follow-up abdominal CT
      examinations of pediatric patients admitted to our institution with documented
      splenic trauma who were managed nonoperatively. Eighty-four patients were
      admitted to our pediatric surgical service with splenic injury documented by CT
      from 1994 through 1998. The standard approach for splenic injury was bedrest for
      5 to 21 days and limited activity for up to 90 days at the discretion of the
      attending surgeon. Thirty-five of the 84 had follow-up CTs during outpatient
      follow-up to evaluate and document splenic healing by CT criteria. The initial
      and follow-up studies were randomized and read blindly by pediatric radiologists
      using a modified American Association for the Surgery of Trauma grading system (I
      V). The age range of the patients was 6 months to 17 years (mean +/- SE; 11 +/- 1
      years). Nineteen (54%) were male and 16 (46%) were female. Causes of splenic
      trauma included motor vehicle accident (22), fall (seven), assault (four),
      pedestrian versus vehicle (one), and sports injury (one). Eight children (23%)
      had grade II injuries, 14 (40%) had grade III injuries, and 13 children (37%) had
      grade IV injuries on initial CT scan. Seven (88%) of the grade II splenic
      injuries were healed by 64 +/- 11 days. The remaining grade II injury had healed
      by 210 days. Thirteen (93%) of the grade III splenic injuries were healed by 76
      +/- 7 days. The remaining grade III injury was healed by 140 days. Spleens in 10
      (77%) of the 13 patients with grade IV injuries were healed by 81 +/- 8 days. Of
      the three remaining grade IV injuries two were healed by 173 +/- 14 days. The
      remaining patient's spleen was radiologically considered to have a grade III
      defect 91 days from the time of injury, and no further CTs were obtained. Of the
      34 patients who underwent follow-up CT imaging until splenic healing was
      demonstrated the mean time to complete healing was 87 +/- 8 days postinjury
      (range 11-217 days). These data suggest that routine follow-up abdominal CTs may
      not be necessary to allow children to resume their normal activities after an
      appropriate time of restricted activity.

PMID- 11243535
TI  - Rectourethral fistula and massive rectal bleeding from iodine-125 prostate
      brachytherapy: a case report.
AB  - Iodine-125 brachytherapy is an effective well-tolerated treatment for localized
      prostate cancer. Gastrointestinal complications of brachytherapy (minor rectal
      bleeding or tenesmus) are uncommon. Rectal ulceration or rectourethral fistulas
      after prostate brachytherapy are rare. We present a case of massive refractory
      rectal bleeding and rectourethral fistula, a complication of prostate
      brachytherapy never before reported. As a result of the patient's life
      threatening symptoms aggressive surgical therapy was necessary.

PMID- 11243536
TI  - Gastrointestinal stromal tumors: analysis of clinical and pathologic factors.
AB  - Gastrointestinal mesenchymal tumors have been classified as benign (leiomyoma) or
      malignant (leiomyosarcomas). More recently, these tumors have been termed
      gastrointestinal stromal tumors (GISTs). GISTs have a highly variable clinical
      course. This review analyzes the clinical presentation, pathologic examination,
      and long-term follow-up of patients with GIST. A retrospective analysis of the
      clinical course of patients with GIST at a single institution from 1986 to 1998
      was performed. Nineteen patients with GIST (12 gastric, two duodenal, three
      jejunal, and two rectal) were treated. The most common clinical presentation was
      gastrointestinal bleed. CT scans, contrast studies, and endoscopy were used to
      identify a tumor mass. Diagnosis of GIST was made in only two patients
      preoperatively. Tumor size ranged from 0.8 to 23 cm. Histology of the tumors was
      variable. All patients underwent surgical resection with curative intent. Follow
      up ranged from 2 to 55 months. There were two perioperative deaths. Local
      recurrence occurred in one patient. GISTs are uncommon. Preoperative diagnosis
      can be difficult, and often the diagnosis is made at the time of surgery. With
      complete resection of the tumor the clinical course is favorable with very few
      local recurrences. Therefore complete resection of the tumor is recommended.

PMID- 11243537
TI  - Nonoperative management of pediatric blunt hepatic trauma.
AB  - The purpose of this study was to examine the effect of operative versus
      nonoperative management of blunt hepatic trauma in children including transfusion
      practices. We reviewed the experience at our American College of Surgeons
      verified Level I trauma center with pediatric commitment over a 5-year period.
      Children < or = 16 years of age suffering blunt liver injury as documented on
      admission CT scan were included in the study. Liver injuries identified on CT
      scan were classified according to the American Association for the Surgery of
      Trauma's Organ Injury Scaling system. All data are presented as mean +/- standard
      error. One case of pediatric liver trauma not identified on CT was excluded
      (prehospital cardiopulmonary resuscitation). Twenty-seven patients were included
      [age 9.3 +/- 1.0 years (range 3-16)]. Mechanisms of injury included motor vehicle
      crash (14), pedestrian struck by motor vehicle (7), bicycle crash (4), fall from
      height (1), and pedestrian struck by falling object (1). Trauma Score was 11.5 +/
      0.3. Distribution of Liver Injury Grade was as follows: grade I, 13; grade II,
      9; grade III, 3; grade IV, 2; and grade V, 0. All five patients who underwent
      operative management had multiple organ injuries; three had concomitant splenic
      injury requiring operative repair; the remaining two had small bowel injury
      requiring repair. Hepatorrhaphy did not correlate with severity of liver injury:
      grade I, n = 1; II, n = 2; III, n = 1; and IV, n = 1. Three operated patients
      received blood transfusions. Twenty-two patients were managed with nonoperative
      treatment, of these only one required blood transfusion. No patients in the study
      died, three were transferred to subacute rehabilitation, one was transferred to
      another hospital, and 23 were discharged home. Our findings indicate that a
      majority of children with blunt hepatic injury as documented on CT scan can be
      managed with nonoperative treatment, and few require blood transfusions. Patients
      with multiple organ injury including simultaneous splenic injury are likely
      ideally managed through operative exploration and repair, whereas those with
      isolated liver injuries can be successfully managed nonoperatively.

PMID- 11243538
TI  - A critical appraisal of treatment for T3N0 colon cancer.
AB  - The purpose of this study was to evaluate the impact of adjuvant chemotherapy on
      survival after surgery for T3N0 colon cancer. All patients with node-negative
      (N0) colon cancer with tumor invasion beyond the muscularis propria (T3) treated
      with colectomy between 1982 and 1995 at a single institution were included.
      Patients were divided into two groups depending on postcolectomy treatment with
      or without adjuvant chemotherapy. Groups were evaluated to determine
      perioperative and pathologic variables that could potentially influence outcome
      and surveillance data to determine disease-free and overall survival. In 253
      patients with T3N0 colon cancer 226 remained under observation and 27 were
      treated with adjuvant chemotherapy. The groups were similar (P = not significant)
      when compared for tumor location, size, differentiation, number of nodes
      harvested, and transfusion requirements. Four of the 27 patients who received
      chemotherapy developed a recurrence (14.8%), whereas 22 of the 226 observation
      patients developed a recurrence (9.7%). Disease-free survival for the
      chemotherapy group at 5 years was 84 per cent and for the observation group 87
      per cent. Statistical analysis (Mantel-Cox) showed no significant difference
      between the groups on the basis of survival (P = 0.3743). We conclude that
      resection alone is a highly effective treatment for T3N0 colon cancer leaving
      limited opportunity for adjuvant chemotherapy to significantly impact survival.
      Adjuvant chemotherapy for T3N0 colon cancer patients should be limited to
      patients enrolled in clinical trials designed to identify subgroups of T3N0 colon
      cancer patients at a survival disadvantage or less toxic adjuvant chemotherapies.

PMID- 11243539
TI  - Nonoperative management of blunt splenic and hepatic trauma in the pediatric
      population: significant differences between adult and pediatric surgeons?
AB  - Although operative management was the preferred method of treating blunt
      abdominal trauma in the past, recent literature and practice recommend a
      nonsurgical approach to most pediatric splenic and hepatic injuries. The majority
      of data supporting the safety and efficacy of this nonoperative approach are
      derived from university trauma programs with a pediatric center where care was
      managed by pediatric surgeons only. To evaluate the applicability of this
      approach in a regional trauma center where pediatric patients are managed by
      pediatric and non-pediatric surgeons we reviewed the experience at a Level II
      community trauma center. Fifty-four children (16 years of age or less) were
      admitted between April 1992 and April 1998 after sustaining blunt traumatic
      splenic and/or hepatic injuries. There were 37 (69%) males and 17 (31%) females;
      the average age was 11 years (range 4 months to 16 years). Of the 54 patients 34
      (63%) sustained splenic injuries, 17 (31%) sustained hepatic injuries, and three
      (6%) sustained both splenic and hepatic injuries. All of these injuries were
      diagnosed by CT scan or during laparotomy. The average Injury Severity Score was
      14.9 with a range from four to 57. Of the 47 patients initially admitted for
      nonoperative management one patient failed nonoperative management and required
      operative intervention. In our study 98 per cent (46 of 47 patients) of pediatric
      patients were successfully managed nonoperatively. Complications of nonoperative
      management occurred in two patients. Both developed splenic pseudocysts after
      splenic injury, which required later operative repair. These data are comparable
      with those from university trauma programs and confirm that nonoperative
      management is safe in a community trauma center. The majority of children with
      blunt splenic and hepatic trauma can be successfully treated without surgery, in
      a regional trauma center treated by nonpediatric trauma surgeons, if the decision
      is based on careful initial evaluation, aggressive resuscitation, and close
      observation of their hemodynamic stability.

PMID- 11243540
TI  - Laparoscopic repair of inguinal hernias with higher risk for recurrence:
      independent assessment of results from 121 repairs.
AB  - This study attempts to determine by independent review the results of
      laparoscopic transabdominal preperitoneal (TAPP) inguinal hernia repair for
      hernias with increased risk for recurrence. Indicators used for increased
      recurrence risk were recurrent hernias or simultaneously repaired bilateral
      inguinal hernias. Office and hospital records of all such patients who had
      undergone TAPP repair were reviewed from one surgeon's 242-patient laparoscopic
      inguinal hernia database from 1992 to 1998. All were called for assessment by an
      independent surgeon at least 4 months postoperatively (median 34 months). Those
      unable to come in person were interviewed by telephone. There were 121 hernias:
      34 recurrent and 100 bilateral (13 overlap). Recurrence rate was 3 per cent,
      which was similar for repair of bilateral and recurrent hernias. All recurrences
      occurred within 3 months of surgery. No unknown recurrence was detected by the
      independent observer. Laparoscopic TAPP inguinal hernia repair, often claimed as
      the method of choice for bilateral and recurrent hernia repair, is indeed a safe
      and effective procedure with a low early recurrent rate in these higher-risk
      situations.

PMID- 11243541
TI  - Embolization for management of hepatic hemangiomas.
AB  - Hemangiomas represent the most common primary tumor of the liver. Clinically the
      significance of these lesions is highly variable. The management of hemangiomas
      is controversial and is intimately related to the size, symptoms, and associated
      comorbidities of the patients who harbor these benign tumors. Series suggest that
      the vast majority of hemangiomas are less than 4 cm, asymptomatic, and clinically
      incidental findings. Symptomatic hemangiomas are large and associated with a
      constellation of vague upper abdominal complaints including pain, mass,
      distention, early satiety, and weight loss. A number of small series of
      surgically treated symptomatic hemangiomas have demonstrated enucleation as a
      safe and effective intervention. We report a collection of case reports using
      embolization as a primary treatment of symptomatic hemangiomas. The first patient
      is a 73-year-old black man previously treated for prostate cancer by radical
      prostatectomy and radiation. He developed weight loss, abdominal fullness, and
      early satiety. His symptoms were attributed to a large left lateral segmental
      liver mass that was biopsy proven to be a hemangioma. The second patient is a 49
      year-old black women who complained of weakness, fatigue, night sweats, and
      anemia. The only abnormality discovered was a large right posterior hemangioma.
      The third patient is a 49-year-old black women with unexplained right upper
      quadrant pain and anemia who was found to have a 19 x 11 x 7.5-cm left hepatic
      hemangioma by CT. All three patients underwent elective treatment of their
      hemangiomas with highly selective hepatic embolization. There were no significant
      complications related to the procedures. Symptoms resolved for all patients
      acutely after treatment. The use of embolization for hepatic hemangiomas provides
      safe and effective treatment of the patient's symptoms while avoiding operative
      intervention, extended hospitalization, or postoperative recuperation. This
      treatment modality should be considered for the symptomatic hemangioma under
      elective conditions.

PMID- 11243542
TI  - Popliteal artery injury associated with knee dislocations.
AB  - Since the Vietnam War experience we have known that there is a high association
      between knee dislocations and popliteal artery injuries. In an effort to improve
      the quality of care we asked whether every patient with a knee dislocation needs
      an arteriogram. This is a retrospective chart review of all injured patients who
      presented to Louisiana State University Health Science Center with knee
      dislocations between January 1, 1993 and March 31, 1998. Twenty-one patients met
      the study criteria. There were no deaths in this series. Twelve patients
      presented with normal palpable pulses. Nine of these 12 patients underwent an
      arteriogram. There was only one abnormal arteriogram (intimal defect) in this
      group. None of the patients who presented with normal pulses were operated on.
      There were no in-hospital complications from this nonoperative management. In the
      group of patients with either diminished pulses or no pulses arteriograms were
      performed on all patients. Fifty-five per cent of these arteriograms were
      abnormal, and one-third of these patients (two) were taken to the operating room
      for repair. In the group of patients who present with knee dislocations and
      normal peripheral vascular examination arteriograms are not helpful.

PMID- 11243543
TI  - Pseudohyperkalemia secondary to postsplenectomy thrombocytosis.
AB  - Hyperkalemia is a regularly encountered electrolyte abnormality. Less commonly
      recognized is pseudohyperkalemia. In vitro clotting results in the release of
      potassium from the formed elements of blood; this falsely elevates the serum
      potassium concentration. Usually attributed to thrombocytosis, leukocytosis, or
      hemolysis it is rarely reported in the postsplenectomy trauma patient. A 49-year
      old man underwent splenectomy for a grade IV splenic injury. He developed an
      elevated serum potassium on postoperative day 16. His renal function remained
      normal, and an active search for causes of hyperkalemia failed to delineate a
      source for his elevated potassium. Pseudohyperkalemia was proposed as an etiology
      and confirmed by analyzing simultaneous serum (5.9 mEq/L) and plasma potassium
      levels (3.9 mEq/L). The serum potassium showed a concomitant rise with the
      evolution of the patient's postsplenectomy thrombocytosis. This is a case report
      of our patient and a literature review of this rarely reported and underestimated
      cause of a potentially serious electrolyte abnormality. We found through our
      patient that pseudohyperkalemia does occur in the postsplenectomy population and
      that this should be included in the differential diagnosis of any patient with an
      elevated serum potassium level and thrombocytosis.

PMID- 11243544
TI  - Vaginal metastasis of colon cancer.
AB  - True vaginal metastases from colonic cancer are exceedingly rare. This often
      signals an ominous prognosis. More frequently the vagina is synchronously
      involved by direct contiguous spread from the colonic lesion. We present a case
      of sigmoid carcinoma with true metastasis to the vagina that was discovered after
      an interval of 3 weeks when vaginal discharge became evident. To our knowledge,
      there are only two other papers in the English language previously documenting
      this phenomenon.

PMID- 11243546
TI  - Wires should not be used routinely on skin scars for mammograms after breast
      conserving surgery.
AB  - The accuracy of skin wire markers on surgical incision scars during mammography
      to locate the primary tumor excision site was prospectively determined for 100
      women. The shortest distance between the excision site and skin scar wire on
      either the craniocaudal or mediolateral oblique projection was 10 mm or greater
      in 48 per cent of patients and 20 mm or greater in 30 per cent of patients. Wire
      markers placed on skin incision scars during mammography after breast-conserving
      surgery are inadequate for the localization of the primary excision site and
      should not be used routinely.

PMID- 11243545
TI  - Benign and solid tumors of the liver: relationship to sex, age, size of tumors,
      and outcome.
AB  - From 1983 through 1997, our center diagnosed 130 cases of benign neoplasms: 27
      with focal nodular hyperplasia (FNH), 25 with hepatic adenoma, 71 with cavernous
      hemangioma, and seven with mixed tumors of different diagnoses. Most often these
      lesions were seen in females [female-to-male ratio (f/m): 5.5/1]. Hepatic
      adenomas and mixed tumors were seen exclusively in females and FNH predominantly
      in females (f/m: 26/1). Hemangiomas, however, were not uncommon in men (f/m:
      52/19) relative to the other tumors (P < 0.001). Furthermore patients with
      hemangioma were older (mean age: 49 years) whereas patients with hepatic adenoma,
      FNH, and mixed tumors were often younger (mean age: 33, 35, and 44 years
      respectively; P < 0.004). Oral contraceptive steroid use was related by 21 of 25
      patients (84%) with hepatic adenoma, 22 of 26 (85%) females with FNH, five of
      seven (71%) females with mixed tumors, and 10 of 52 (19%) patients with
      hemangioma. Ninety-five of the 130 patients (73%) had one or more symptoms. There
      was no statistically significant correlation between symptoms and the size of the
      lesion, the final diagnosis, and whether there were solitary or multiple masses.
      Three of 25 (12%) with hepatic adenoma presented with rupture, and one of 27 (4%)
      with FNH had such a consequence. None of the hemangiomas presented with rupture
      or progressed to such a state. One patient with hepatic adenoma (4%) had a focus
      of malignancy. Surgical removal of benign tumors was performed in 82 of 130
      patients (63%), and there was one operative mortality (1.2%) in a patient who had
      a caudate lobe FNH. The types of surgical procedures included segmentectomy
      (62%), lobectomy (34%), and trisegmentectomy (4%). In two of 84 patients who had
      undergone laparotomy resection was not technically possible. Resection is
      recommended in all cases of hepatic adenoma because of fear of rupture or
      associated focus of malignancy. FNH was not observed to undergo a malignant
      transformation and will rarely rupture. Surgery is only recommended for
      symptomatic hemangioma, and size of the lesion is not a criterion for excision.

PMID- 11243547
TI  - Hereditary chronic pancreatitis: implications for surgical treatment and follow
      up.
AB  - Hereditary pancreatitis is an uncommon cause of chronic pancreatitis in Western
      society. It should be suspected when chronic pancreatitis presents in young
      adults. The diagnosis is made when chronic pancreatitis is present in several
      members of the same family who are determined not to have other risk factors for
      chronic pancreatitis. Molecular research focusing on mutations in the trypsinogen
      gene has uncovered the genetic defects associated with hereditary pancreatitis,
      and this knowledge has suggested the possible pathophysiologic mechanism of this
      disease. Because patients with hereditary pancreatitis develop their disease
      early in life they are very likely to require treatment for complications. As in
      patients with chronic pancreatitis of other etiologies those with hereditary
      pancreatitis should be treated medically for acute exacerbations. When
      complications occur or when the disease causes intractable pain surgery is
      recommended. Surgical therapy is tailored to the patient's pancreatic anatomy
      based on endoscopic retrograde cholangiopancreatography or CT scan. The two
      patients described in this report underwent successful longitudinal
      pancreaticojejunostomy (Puestow procedure) with good results. Finally it has been
      shown that patients with hereditary pancreatitis are at increased risk for
      developing pancreatic adenocarcinoma. Although not widely used pancreatic cancer
      screening programs have been suggested for surveillance of these patients.

PMID- 11243548
TI  - Necrotizing fasciitis developing from a brown recluse spider bite.
AB  - A 20-year retrospective case series was analyzed to identify the brown recluse
      spider bite as a cause of necrotizing fasciitis. Data from 31 consecutive
      patients with necrotizing fasciitis were analyzed. Of the 31 patients with
      necrotizing fasciitis a brown recluse spider bite was found to be the initial
      cause in two patients. Both patients with spider bites delayed in obtaining
      medical treatment, and secondary infection of the necrotic tissue occurred. One
      patient was diagnosed by frozen section tissue biopsy, and the second patient was
      diagnosed by clinical examination. All patients in this series had immediate
      aggressive operative debridement. Both patients survived with functional limbs.
      There were no deaths in this large series. Necrotizing fasciitis can be caused by
      a secondarily infected brown recluse spider bite. Successful treatment of
      necrotizing fasciitis from any cause is associated with early diagnosis,
      immediate surgical debridement, and supplemental enteral or parenteral nutrition.

PMID- 11243549
TI  - Typical versus atypical presentation of obturator hernia.
AB  - Although it is a rare occurrence among all pelvic hernias diagnosed the obturator
      hernia continues to be a diagnostic challenge for surgeons today. These patients,
      who often have multiple concurrent medical problems, are subject to high
      morbidity and mortality rates resulting from late presentation and delayed
      surgical intervention. The vast majority of patients with obturator hernias are
      admitted with signs and symptoms of intestinal obstruction, namely anorexia,
      nausea, vomiting, constipation, and distension of 2 to 3 days' duration. In this
      paper, however, we highlight a small subset of obturator hernia patients who
      present without obstructive symptoms and do well after elective repair. The case
      reports that follow serve to compare and contrast two very different
      presentations of this surgical problem.

PMID- 11243550
TI  - Monet's cataract surgery.

PMID- 11243551
TI  - Re: Heartburn is more likely to recur after Toupet fundoplication than Nissen
      fundoplication.

PMID- 11243552
TI  - Reliability.

PMID- 11243553
TI  - Information overload in rehabilitation: how to keep up without getting down.

PMID- 11243554
TI  - Goniometry of the proximal and distal interphalangeal joints, Part I: a survey of
      instrumentation and placement preferences.
AB  - A telephone survey of 231 occupational and physical therapists was conducted to
      determine goniometric instrumentation and placement preferences for measuring the
      proximal and distal interphalangeal joints of the upper extremity. The variables
      included were academic degree, hand therapy certification, years of therapy
      experience, years of specialty hand experience, and preferences for goniometric
      instrumentation and placement. Descriptive statistics revealed a highly
      experienced population (mean, 11 years) who predominantly preferred the 6" cut
      off clear and metal goniometers. Eight additional instruments were also noted.
      Dorsal placement of the goniometer was preferred by 73% of the practitioners.
      Lateral placement was occasionally preferred (by 20%) in difficult clinical
      situations. Seven percent of the practitioners reported always preferring the
      lateral method. Chi-square analyses revealed no significant relationships between
      the variables.

PMID- 11243555
TI  - Goniometry of the proximal and distal interphalangeal joints, Part II: placement
      prefereces, interrater reliability, and concurrent validity.
AB  - The purposes of this repeated-measures single-case-design study were to describe
      goniometric placement preferences and their effect on the measurement of the
      proximal and distal interphalangeal joints, to determine interrater reliability,
      and to determine concurrent validity. Thirty-nine therapists measured one patient
      dorsally and laterally with the DeVore and the 6" clear goniometers. No
      significant differences were found between the two goniometers used in the study.
      Comparison of the means of lateral and dorsal measurements revealed that the only
      joint associated with a significant difference was the contracted index proximal
      interphalangeal joint (p=0.0347). Preferences did affect the standard deviations
      and ranges but not the means of the measurements. Interrater reliability was high
      (ICC 2,1: 0.99 and 0.86). Clinical and radiographic measurements were markedly
      different from each other (paired-difference t-tests), leading to inconclusive
      concurrent validity.

PMID- 11243556
TI  - Hand therapy: the healing touch with a touch of humor!

PMID- 11243557
TI  - Intrarater reliability of a new method and instrumentation for measuring passive
      supination and pronation: a preliminary study.
AB  - Because of the clinical impression that traditional forearm goniometry has
      several potential sources of error and is therefore inherently unreliable, a new
      method using a newly designed goniometer was compared with traditional forearm
      passive range-of-motion goniometry. The new method utilized an offset face with a
      plumbline design and a patient-held tubular handle. Thirty orthopedic patients
      (31 wrists) were measured by three experienced hand therapists in a test-retest
      protocol to determine the reliability of both the traditional and new methods.
      Both the intraclass correlation coefficients and standard error of the measure
      showed improved scores with the new goniometric technique, compared with the
      traditional one. The differences between methods may not be clinically
      significant.

PMID- 11243558
TI  - Inter-instrument reliability of pinch strength scores.
AB  - The consistency of pinch scores obtained with new devices compared with that of
      scores obtained by traditional devices underlies the ability of therapists to use
      new devices when communicating about patient status or using normative data
      published for these traditional devices. This study determined the inter
      instrument reliability of pinch strength scores obtained using three commercially
      available pinch gauges (B&L, JTech and NK pinch gauges). Volunteers (average age,
      32 years; range, 18 to 80 years; 19 women, 21 men; 20 with hand pathology, 20
      without hand pathology) were tested on a single occasion using all three devices.
      Each subject was tested with the elbow at 90%, the forearm neutral, and the wrist
      in neutral deviation. Three trials of maximum tripod and key pinch strength were
      performed. The hand tested first and the instrument order were randomized.
      Intraclass correlation coefficients (ICCs) and their 95% confidence intervals
      were calculated. The inter-instrument error and its associated boundaries (+/- 2
      SD) were also calculated. Intraclass correlation coefficients were high for both
      affected and unaffected hands in patients (> 0.90) and in subjects without
      pathology (> 0.80). Average instrument error was close to zero and was similar
      between instruments, indicating a lack of instrument bias. These results suggest
      that pinch strength scores obtained with any of these three pinch gauges can be
      compared with normative data obtained with either of the other pinch gauges.

PMID- 11243559
TI  - Postoperative management of functionally restrictive muscular adherence, a
      corollary to surgical tenolysis: a case report.
AB  - After a surgical release of adhered nongliding tendons, early active mobilization
      is encouraged to prevent the reformation of unfavorable adhesions that would
      limit functional tendon excursion. These restricting adhesions can also occur in
      non-synovial regions, such as within the flexor mass in the forearm. A
      "myolysis," or release of muscle fibers from tethering adhesions, can be
      performed surgically to restore the muscle's gliding and lengthening properties.
      Postoperative management consists of treatment techniques that include low-load
      prolonged stress, differential tendon gliding, and active-resistive exercises,
      all of which are effective in restoring and maximizing a patient's active and
      passive range of motion to allow optimal mobility and performance. This case
      study demonstrates the successful management of a patient following a surgical
      myolysis, utilizing treatment techniques conceptually derived from postoperative
      tenolysis rehabilitation.

PMID- 11243560
TI  - The dynamic intraphalangeal final flexion splint.

PMID- 11243561
TI  - Critical literature reviews.

PMID- 11243562
TI  - Rhein, an active metabolite of diacerein, suppresses the interleukin-1alpha
      induced proteoglycan degradation in cultured rabbit articular chondrocytes.
AB  - Diacerein has proved to be effective in the treatment of osteoarthritis. We
      investigated the effects of rhein, an active metabolite of diacerein, on the
      degradation of recombinant human interleukin-1alpha (rhIL-1alpha)-induced
      proteoglycan and matrix metalloproteinases (MMPs) release from rabbit articular
      chondrocytes. Chondrocytes were treated for 24 h with rhein in the presence of
      rhIL-1alpha. Rhein suppressed the rhIL-1alpha-induced proteoglycan degradation.
      In addition, rhein decreased the rhIL-1alpha-induced proMMP-3 production and
      reduced the MMPs activity. These results suggested that diacerein might have a
      protective effect on proteoglycan degradation via the suppressive effect of rhein
      on the production of proMMPs.

PMID- 11243563
TI  - Guinea pig histamine N-methyltransferase: cDNA cloning and mRNA distribution.
AB  - We report here the isolation of histamine N-methyltransferase (HMT) cDNA from the
      guinea pig brain by the polymerase chain reaction on the basis of nucleotide
      sequences of rat and human counterparts. Guinea pig HMT consists of 292 amino
      acids, with homologies of 75.6% and 79.1% to rat and human HMT, respectively.
      Northern blotting analysis indicated that the 1.6-kb guinea pig HMT transcript
      was expressed at various levels in different tissues at the following relative
      abundance: jejunum, brain > lung, spleen, stomach > liver, kidney. HMT mRNA
      localized throughout the jejunum, and it was mainly expressed in epithelial cells
      and in Auerbach's plexus.

PMID- 11243564
TI  - Is compensatory vasoconstrictor tone in the hindquarter vascular region induced
      by hemorrhage in conscious spontaneously hypertensive rats?
AB  - We investigated whether a compensatory vasoconstrictor action would be induced by
      a hypotensive intervention in the hindquarter vascular region of conscious
      spontaneously hypertensive rats (SHRs). Mean arterial pressure and hindquarter
      blood flow were recorded. After hemorrhage (withdrawing blood, 0.3 ml/100 g body
      weight), hindquarter resistance (HQR) was increased significantly. The decrease
      in HQR induced by the administration of a ganglionic blocker (C6; 25 mg/kg, i.v.)
      was significantly greater in SHRs with hemorrhage than in those without
      hemorrhage. The present results suggest that a detectable hindquarter compensator
      tone occurs due to hemorrhage in SHRs, although an abnormal substantial
      vasoconstrictor tone already exists in the hindquarters.

PMID- 11243565
TI  - An independent non-neuronal cholinergic system in lymphocytes.
AB  - Acetylcholine (ACh) is a well characterized neurotransmitter occurring throughout
      the animal kingdom. In addition, both muscarinic and nicotinic ACh receptors have
      been identified on lymphocytes of various origin, and their stimulation by
      muscarinic or nicotinic agonists elicits a variety of functional and biochemical
      effects. It was thus initially postulated that the parasympathetic nervous system
      may play a role in modulating immune system function. However, ACh in the blood
      has now been localized to lymphocytes; indeed expression of choline
      acetyltransferase (ChAT), an ACh synthesizing enzyme, has been shown in human
      blood mononuclear leukocytes, human leukemic T-cell lines and rat lymphocytes.
      Stimulation of T-lymphocytes with phytohemagglutinin activates the lymphoid
      cholinergic system, as evidenced by increased synthesis and release of ACh and
      increased expression of mRNAs encoding ChAT and ACh receptors. The observation
      that M3 muscarinic receptor stimulation by ACh and other agonists increases the
      intracellular free Ca2+ concentration and upregulates c-fos gene expression
      strongly argues that ACh, synthesized and released from T-lymphocytes, acts as an
      autocrine and/or paracrine factor regulating immune function. These findings
      present a compelling picture in which immune function is, at least in part, under
      the control of an independent lymphoid cholinergic system.

PMID- 11243566
TI  - Effect of prolonged nitric oxide synthesis inhibition on plasma fibrinogen
      concentration in rats.
AB  - We examined whether nitro-L-arginine-methyl ester (L-NAME) causes a sustained
      elevation in plasma fibrinogen concentration in rats. Oral dosing of L-NAME (100
      mg/kg per day) for 7 days significantly raised plasma fibrinogen concentration in
      rats. The increase in plasma fibrinogen, however, returned to control levels by
      the treatment for more than 7 days, in spite of progressive hypertension.
      Candesartan failed to reverse the transient hyperfibrinogenemia, indicating that
      the rise in plasma fibrinogen may occur through the mechanisms other than
      angiotensin II receptor activation. These data suggest that a prolonged L-NAME
      treatment does not cause chronic hyperfibrinogenemia in rats.

PMID- 11243568
TI  - The biological role of non-neuronal acetylcholine in plants and humans.
AB  - Acetylcholine, one of the most exemplary neurotransmitters, has been detected in
      bacteria, algae, protozoa, tubellariae and primitive plants, suggesting an
      extremely early appearance in the evolutionary process and a wide expression in
      non-neuronal cells. In plants (Urtica dioica), acetylcholine is involved in the
      regulation of water resorption and photosynthesis. In humans, acetylcholine
      and/or the synthesizing enzyme, choline acetyltransferase, have been demonstrated
      in epithelial (airways, alimentary tract, urogenital tract, epidermis),
      mesothelial (pleura, pericardium), endothelial, muscle and immune cells
      (granulocytes, lymphocytes, macrophages, mast cells). The widespread expression
      of non-neuronal acetylcholine is accompanied by the ubiquitous expression of
      cholinesterase and acetylcholine sensitive receptors (nicotinic, muscarinic).
      Both receptor populations interact with more or less all cellular signalling
      pathways. Thus, non-neuronal acetylcholine can be involved in the regulation of
      basic cell functions like gene expression, proliferation, differentiation,
      cytoskeletal organization, cell-cell contact (tight and gap junctions,
      desmosomes), locomotion, migration, ciliary activity, electrical activity,
      secretion and absorption. Non-neuronal acetylcholine also plays a role in the
      control of unspecific and specific immune functions. Future experiments should be
      designed to analyze the cellular effects of acetylcholine in greater detail and
      to illuminate the involvement of the non-neuronal cholinergic system in the
      pathogenesis of diseases such as acute and chronic inflammation, local and
      systemic infection, dementia, atherosclerosis, and finally cancer.

PMID- 11243567
TI  - Roles of muscarinic acetylcholine receptors in interleukin-2 synthesis in
      lymphocytes.
AB  - Receptors for many neurotransmitters including catecholamines and acetylcholine
      (ACh) have been detected on the cell surface of lymphocytes. It has been
      demonstrated that a human T cell line synthesizes ACh and suggested that ACh may
      be an autacoid modulating T cell-dependent immune responses. However, the
      biochemical interactions of the ACh system with the immune system have not been
      elucidated in detail. We have shown that m1 and m2 muscarinic receptor mRNAs are
      expressed in human peripheral blood lymphocytes and in human T cell line Jurkat
      cells and that pretreatment of these cells with a muscarinic receptor agonist
      enhances interleukin-2 (IL-2) production. We also postulated possible
      intracellular signaling pathways via which muscarinic receptors regulate IL-2
      production in Jurkat cells. The findings suggest that M1 muscarinic receptors are
      involved in muscarinic receptor-mediated enhancement of IL-2 production in Jurkat
      cells and that the transcription factor AP-1 and pathways via mitogen-activated
      protein kinase (MAPK)/extracellular signal regulated protein kinase and c-Jun N
      terminal kinase, but not via p38 MAPK, may be involved in the muscarinic receptor
      mediated enhancement of IL-2 production. Our findings demonstrate a neuro-immune
      interaction through muscarinic receptor signaling in immune cells.

PMID- 11243569
TI  - Non-neuronal neurotransmitters and neurotrophic factors in amniotic epithelial
      cells: expression and function in humans and monkey.
AB  - Human amniotic epithelial cells (HAEC) are formed from epiblasts on the 8th day
      after fertilization. Because they lack major histocompatibility complex (MHC)
      antigen, human amniotic tissue transplantation has been used for
      allotranplantation to treat patients with lysosomal diseases. We have provided
      evidence that HAEC have multiple functions such as synthesis and release of
      acetylcholine (ACh) and catecholamine (CA) as well as expressing mRNA coding for
      dopamine receptors and dopamine (DA) transporter (DAT). On the other hand, we
      showed that monkey amniotic epithelial cells (MAEC) synthesize and release CA and
      posses DA receptors and DAT. Detection of muscarinic actylcholine receptors
      indicates the presence of an autocrine mechanism in HAEC. Recently, we found that
      HAEC have neurotrophic function in conditioned medium from HAEC, indicating the
      presence of a novel neurotrohpic factor that is synthesized and released from
      HAEC. The amniotic membrane may have a significant role in supplying neurotrophic
      factors as well as neurotransmitters to the amniotic fluid, suggesting an
      important function in the early stages of neural development of the embryo. This
      review will focus on the neuropharmacological aspects of HAEC and MAEC in
      relation to the physiology of amniotic membrane.

PMID- 11243570
TI  - The non-neuronal cholinergic system in the endothelium: evidence and possible
      pathobiological significance.
AB  - An increasing body of knowledge indicates that the cholinergic system is not
      confined to the nervous system, but is practically ubiquitous. The present paper
      will address the question of the non-neuronal cholinergic system in vascular
      endothelial cells (EC). In tissue sections of human skin, immunohistochemical
      studies using confocal laser scanning microscopy showed ChAT (choline
      acetyltransferase) activity in the EC of dermal blood vessels. Positive ChAT
      immunoreactivity was also demonstrated in monolayer cultures of human umbilical
      vein EC (HUVEC) and a human angiosarcoma EC line (HAEND). That the synthesizing
      enzyme is not only present in EC, but also active was shown by measuring ChAT
      activity. Thus, in HUVEC cultures, ChAT activity amounted to 0.78 +/- 0.15 nmol x
      mg protein(-1) x h(-1) (n = 3), but was only partially (about 50%) inhibited by
      the ChAT inhibitor bromoacetylcholine (30 microM). In HPLC measurements, a
      concentration of 22 +/- 2 pmol acetylcholine (ACh) per 10(6) cells was found (n =
      6). However, using a cholinesterase-packed analytical column to check the
      identity of the acetylcholine peak, the peak height was found to be reduced,
      although a significant peak still remained, indicating the existence of a
      compound closely related to ACh. Further immunocytochemical experiments indicated
      that EC in vitro also express the vesicular acetylcholine transporter (VAChT)
      system. Preliminary immunoelectron microscopic studies suggest a topographical
      association of VAChT with endothelial endocytotic vesicles. The presented
      experiments clearly demonstrate the existence of essential elements of the
      cholinergic system (ChAT, VAChT, ACh) in the human endothelium. The biological
      functions of ACh synthesized by endothelial cells are the focus of ongoing
      research activity.

PMID- 11243571
TI  - The role of oxygen-derived free radicals in augmented relaxations to
      levcromakalim in the aorta from hypertensive rats.
AB  - Hydrogen peroxide and peroxynitrite induce relaxations via ATP-sensitive K+
      channels, indicating that oxygen-derived free radicals may activate these
      channels. Levels of free radicals are increased throughout the arterial wall in
      animal models of atherosclerosis, and therefore, vasorelaxation via ATP-sensitive
      K+ channels may be augmented in chronic hypertension. The present study was
      designed to determine whether relaxations to an ATP-sensitive K+ channel opener,
      levcromakalim, are increased in the aorta from spontaneously hypertensive rats
      (SHR) and whether free radical scavengers reduce these relaxations. Rings of
      aortas without endothelium taken from age-matched Wistar-Kyoto rats (WKY) and SHR
      were suspended for isometric force recording. Relaxations to levcromakalim (10(
      8) to 10(-5) M), which are abolished by glibenclamide (10(-5) M), were augmented
      in the aorta from SHR, compared to those in the aorta from WKY. In the aorta from
      SHR, catalase (1200 U/ml), but neither superoxide dismutase (150 U/ml) nor
      deferoxamine (10(-4) M), reduced relaxations to levcromakalim, whereas in the
      aorta from WKY, the free radical scavengers did not affect these relaxations.
      These results suggest that in chronic hypertension, vasorelaxation to an ATP
      sensitive K+ channel opener is augmented and that hydrogen peroxide produced in
      smooth muscle cells may partly contribute to these relaxations.

PMID- 11243572
TI  - (+/-)-Pindolol acts as a partial agonist at atypical beta-adrenoceptors in the
      guinea pig duodenum.
AB  - The agonistic and antagonistic effects of (+/-)-pindolol (1-(1H-indol-4-yloxy)-3
      [(1-methylethyl)amino]-2-propanol) were estimated to clarify whether (+/-)
      pindolol acts as a partial agonist on atypical beta-adrenoceptors in the guinea
      pig duodenum. (+/-)-Pindolol induced concentration-dependent relaxation with a
      pD2 value of 5.10 +/- 0.03 and an intrinsic activity of 0.83 +/- 0.03. However,
      the relaxations to (+/-)-pindolol were not antagonized by the non-selective beta1
      and beta2-adrenoceptor antagonist (+/-)-propranolol (1 microM). In the presence
      of (+/-)-propranolol (1 microM), the non-selective beta1-, beta2- and beta3
      adrenoceptor antagonist (+/-)-bupranolol (30 microM) induced a rightward shift of
      the concentration-response curves for (+/-)-pindolol (apparent pA2 = 5.41 +/-
      0.06). In the presence of (+/-)-propranolol, (+/-)-pindolol (10 microM) weakly
      but significantly antagonized the relaxant effects to catecholamines ((-)
      isoprenaline, (-)-noradrenaline and (-)-adrenaline), a selective beta3
      adrenoceptor agonist BRL37344 ((R*,R*)-(+/-)-4-[2-[(2-(3-chlorophenyl)-2
      hydroxyethyl) amino]propyl]phenoxyacetic acid sodium salt) and a non-conventional
      partial beta3-adrenoceptor agonist (+/-)-CGP12177A([4-[3-[(1,1
      dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one]
      hydrochloride). These results demonstrate that (+/-)-pindolol possesses both
      agonistic and antagonistic effects on atypical beta-adrenoceptors in the guinea
      pig duodenum.

PMID- 11243573
TI  - Characterization of prejunctional purinoceptors inhibiting noradrenaline release
      in rat mesenteric arteries.
AB  - The effects of purinoceptor agonists on noradrenaline NA release by electrical
      stimulation in rat mesenteric arteries were examined to clarify the
      pharmacological properties of prejunctional purinoceptors on adrenergic nerves.
      Adenosine and the other P1-receptor agonists, 5'-(N-ethylcarboxamido) adenosine
      and 2-chloroadenosine, significantly inhibited the release of NA. Also beta,gamma
      methylene ATP and 2-methylthio ATP, P2-receptor agonists, significantly inhibited
      NA releases. The inhibitory effect of adenosine was significantly reduced by
      adenosine deaminase, but those of beta,gamma-methylene ATP and 2-methylthio ATP
      were not affected. This suggests that the inhibitory effects of P2-receptor
      agonists are not due to conversion into adenosine. 1,3-Dipropyl-8
      cyclopentylxanthine (DPCPX), a P1 (A1)-receptor antagonist, significantly reduced
      the inhibitory effects of not only the P1- but also P2-receptor agonists.
      Therefore, DPCPX appears to act on both prejunctional P1- and P2-receptor as an
      antagonist. Pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), a P2
      receptor antagonist, significantly reduced the inhibitory effects of the P2
      receptor agonists, but not those of the P1-receptor agonists. From these findings
      in the rat mesenteric artery, the P1-receptor agonist-induced inhibition of NA
      release appears to be mediated via a well-known prejunctional P1-receptor of the
      A1-subtype, but the P2-receptor agonist-induced inhibition appears to be mediated
      via an unidentified purinoceptor that is blocked not only by P2-receptor
      antagonists but also by P1-receptor antagonists.

PMID- 11243574
TI  - Mechanisms underlying the induction of vasorelaxation in rat thoracic aorta by
      sanguinarine.
AB  - In the present study, the effect of sanguinarine (SANG) on smooth muscle was
      investigated in thoracic aorta isolated from rats. SANG dose-dependently relaxed
      the phenylephrine (PE, 3 microM)-precontracted aorta; and the concentrations to
      produce 50% relaxation were 3.18 +/- 0.37 and 3.42 +/- 1.14 microM, respectively,
      in intact and denuded aorta. These results suggest that the relaxing effect of
      SANG was endothelium-independent. The total contraction induced by PE was
      inhibited in aorta pretreated with SANG at microM concentration. Both phasic and
      tonic contractions induced by PE were inhibited by SANG independently, which were
      further supported by the fact that inositol 1,4,5-trisphosphate (IP3) formation
      and 45Ca2+ influx induced by 3 microM PE in denuded aorta were inhibited by SANG
      concentration-dependently. In addition, the vasocontraction induced by high-K+
      was also inhibited by SANG, however, at higher concentrations. The inhibitory
      effects of SANG were reversed by dithiothreitol, a thiol reducing agent, implying
      that the oxidation of critical sulfhydryl groups on key molecules that regulate
      the smooth muscle contraction were involved. These data suggested that the
      inhibitory effects of SANG on PE-induced vasocontraction might involve the
      inhibition of IP3 formation and blockade of calcium channel.

PMID- 11243575
TI  - Modulation by cyclic AMP and phorbol myristate acetate of cephaloridine-induced
      injury in rat renal cortical slices.
AB  - Intracellular signaling pathways of cAMP and protein kinase C (PKC) have been
      suggested to modulate the generation of free radicals. We investigated the
      effects of cAMP and phorbol myristate acetate (PMA), a PKC activator, on
      cephaloridine (CER)-induced renal cell injury, which has been reported to be due
      to the generation of free radicals. Incubation of rat renal cortical slices with
      CER resulted in increases in lipid peroxidation and lactate dehydrogenase (LDH)
      release and in decreases in gluconeogenesis and p-aminohippurate (PAH)
      accumulation in rat renal cortical slices, suggesting free radical-induced injury
      in slices exposed to CER. A derivative of cAMP ameliorated not only the increase
      in lipid peroxidation but also the renal cell damage induced by CER. This
      amelioration by a cAMP derivative of lipid peroxidation and renal cell damage
      caused by CER was blocked by KT 5720, a protein kinase A (PKA) inhibitor. Lipid
      peroxidation and the indices of cell injury were increased by PMA. PMA also
      enhanced CER-induced lipid peroxidation and cell damage in the slices. This
      enhancement by PMA of CER-induced injury was blocked by H-7, a PKC inhibitor.
      These results indicated that intracellular signaling pathways of cAMP and PKC
      modulate free radical-mediated nephrotoxicity induced by CER.

PMID- 11243576
TI  - Existence of retinoic acid-receptor-independent retinoid X-receptor-dependent
      pathway in myeloid cell function.
AB  - We previously reported that ER-27191 (4-[4,5,7,8,9,10-hexahydro-7,7,10,10
      tetramethyl-1-(3-pyridylmethyl)anthra[1,2-b]pyrrol-3-yl]benzoic acid) is a potent
      antagonist of retinoic acid receptor (RAR), and ER-35795 ((2E,4E,6E)-7-[1-(1
      methylethyl)-8-chloro-1,2,3,4-tetrahydroquinolin-6-yl]-6-fluoro-3-methyl-2,4,6
      nonatrienoic acid) is a novel retinoid X receptor (RXR)-specific agonist. By
      using these compounds, we investigated whether distinct RAR-dependent and RXR
      dependent pathways operate to mediate the diverse activities of retinoids,
      particularly, the effects of the RXR pathway on cellular function. ER-27191
      completely antagonized HL60 cell differentiation induced by all-trans-retinoic
      acid (atRA). However, the differentiation induced by the ER-35795 was not
      antagonized at all by the RAR antagonist, but was inhibited by an RXR homodimer
      antagonist (LGD100754, (2E,4E,6Z)-7-(3-n-propoxy-5,6,7,8-tetrahydro-5,5,8,8
      tetramethylnaphthalen-2-yl)-3-methylocta-2,4,6-trienoic acid). Its agonistic
      action on RXR/RAR heterodimer, on the other hand, was neutralized by the RAR
      antagonist. During HL60 cell differentiation, atRA induced RARbeta mRNA, while
      the RXR had no effect. Interestingly, a functional RXR-pathway was also seen in
      lipopolysaccharide-induced inhibition of mouse splenocyte proliferation. These
      results strongly suggest the existence of a pharmacological RXR-dependent pathway
      that is activated by a ligand that can bind to RXR.

PMID- 11243577
TI  - Possible involvement of 5-HT4 receptors, in addition to 5-HT3 receptors, in the
      emesis induced by high-dose cisplatin in Suncus murinus.
AB  - To clarify the mechanism for the severe emesis concomitant with intensive
      chemotherapy, we investigated the effects of 5-HT3- and 5-HT4-receptor
      antagonists on the emesis induced by the high-dose of cisplatin in Suncus
      murinus. The emesis induced by 50 mg/kg of cisplatin was reduced by the oral
      pretreatment with tropisetron, which is known as a 5-HT3- and 5-HT4-receptor dual
      antagonist in vitro, with the ID50 value of 0.52 mg/kg. On the contrary,
      granisetron, a selective 5-HT3-receptor antagonist, did not markedly inhibit the
      emesis at up to 30 mg/kg. Moreover, GR125487, a selective 5-HT4-receptor
      antagonist, did not inhibit the emesis. However, co-administration of GR125487
      and granisetron significantly reduced the number of emetic episodes. The study of
      the co-administration of GR125487 with tropisetron showed that GR125487 did not
      further enhance the inhibitory effect of tropisetron alone, suggesting that the
      anti-emetic effect of tropisetron is mediated via the blockade of both 5-HT3 and
      5-HT4 receptors. These results suggest that both the 5-HT3 and 5-HT4 receptors
      are involved in the emesis induced by the high-dose of cisplatin in Suncus
      murinus.

PMID- 11243578
TI  - Species- and temperature-dependency of the decrease in myofilament Ca2+
      sensitivity induced by beta-adrenergic stimulation.
AB  - Although beta-adrenergic stimulation has been shown in many studies to decrease
      myofilament Ca2+ sensitivity in various types of cardiac muscle such as rat and
      rabbit ventricles, other studies disagree with this conclusion. In the present
      study, we aimed to explain these contradictory findings. We examined the effect
      of beta-adrenoceptor stimulation on Ca2+ sensitivity using guinea pig and rat
      ventricles. We performed the experiment at two different temperatures and
      compared the results. In guinea pig ventricles, isoproterenol and forskolin did
      not alter the relationship between [Ca2+]i and muscle force during the relaxation
      phase of tetanic contraction at either 24 degrees C or 30 degrees C. In rat
      ventricles, in contrast, isoproterenol shifted the [Ca2+]i-force curve to the
      right at 24 degrees C, but not at 30 degrees C. In guinea pig ventricles
      permeabilized by alpha-toxin, in which the cAMP/PK-A system is intact, the
      addition of cAMP did not decrease Ca2+ sensitivity. These results suggest that
      there are species- and temperature-dependent differences in the regulation of
      myofilament Ca2+ sensitivity by beta-adrenergic stimulation.

PMID- 11243579
TI  - Suppression of gingival inflammation induced by Porphyromonas gingivalis in rats
      by leupeptin.
AB  - In this study, we developed a procedure to produce gingivitis in rats by
      inoculation of Porphyromonas gingivalis and studied the contribution of the
      bacterial cysteine proteinases, Arg-gingipain (Rgp) and Lys-gingipain (Kgp), to
      the pathology in the gingiva. To adhere the bacterium to periodontal tissues, a
      cotton thread was inserted between the first and second molar of right maxillary
      sites of rats. Rats in group A were administered with vehicle alone after
      bacterial (strain W83) inoculation. In group B, the bacteria were inoculated in
      combination with leupeptin, a potent inhibitor of Rgp and Kgp, and then leupeptin
      alone was administered the week after. Rats in group C were administered
      leupeptin for 6 weeks after bacteria inoculation. All left maxillary gingiva in
      three groups showed no inflammatory changes. Right maxillary gingiva of group A
      showed most of the clinical landmarks of gingivitis. Leupeptin exhibited only a
      little inhibitory effect on this gingivitis in group B, whereas it had a strong
      inhibitory effect on the inflammation in group C. These results suggest that P.
      gingivalis-induced gingivitis is attributable to Rgp and Kgp and that leupeptin
      is more effective in the late phase than the early stage of gingivitis.

PMID- 11243580
TI  - The role of nitrergic system in lidocaine-induced convulsion in the mouse.
AB  - The effects of N-nitro-L-arginine-methyl ester (L-NAME) a nitric oxide (NO)
      synthase inhibitor and L-arginine, a NO precursor, were investigated on lidocaine
      induced convulsions. In the first experiment, four groups of mice received
      physiological saline (0.9%), L-arginine (300 mg/kg, i.p.), L-NAME (100 mg/kg,
      i.p.) and diazepam (2 mg/kg), respectively. Thirty minutes after these
      injections, all mice received lidocaine (50 mg/kg, i.p.). In the second
      experiment, four groups of mice received similar treatment in the first
      experiment, and 30 min after these injections, all mice received a higher dose of
      lidocaine (80 mg/kg). L-NAME (100 mg/kg, i.p.) and diazepam (2 mg/kg)
      significantly decreased the incidence of lidocaine (50 mg/kg)-induced
      convulsions. In contrast, the L-arginine treatment increased the incidence of
      lidocaine (80 mg/kg, i.p.)-induced convulsions significantly. These results may
      suggest that NO is a proconvulsant mediator in lidocaine-induced convulsions.

PMID- 11243581
TI  - Inhibition of concanavalin A-induced mice hepatitis by coumarin derivatives.
AB  - The effects of coumarin derivatives, osthole, imperatorin, Pd-Ia, Pd-II and Pd
      III, on mice concanavalin A (Con A) (0.2 mg/mouse, i.v.)-induced hepatitis were
      studied. At the dose of 200 mg/kg (i.p.), these coumarins inhibited more than 90%
      of the Con A-induced elevation of plasma alanine aminotransferase activity, but
      glycyrrhizin (200 mg/kg, i.p.) caused only 45% inhibition. At the dose of 100
      mg/kg (i.p.), osthole produced the strongest inhibition among these coumarins.
      The inhibitory activity of osthole is lost when its 7-methoxy group is replaced
      by a 7-hydroxy group to form osthenol. The present results showed that coumarin
      derivatives inhibited Con A-induced hepatitis, with osthole being the most
      inhibitory.

PMID- 11243583
TI  - Methods of mortality (incidence) rates interpretation assessment in small
      populations.
AB  - Findings and procedures include in this article have been realized at Regional
      Public Health Office in Hradec Kralove (Czech Republic) within the period from
      August 1999 to February 2000. The model sample used in this article dealed only
      with events of neoplasms incidence in men's population in the region of Eastern
      Bohemia within the period from 1986 to 1997. The original experimental part
      concerned to the use of procedures for demographical data standardization for
      target group of "small populations" including of their selection and spatial
      distribution. As the result of it, there are topical maps of spatial distribution
      of incidence (event. mortality) of selected diagnoses according to sex with
      target area units delimitated by methods of regional geography with around 120
      km2 and total average number about 10000 inhabitants. Thanks to using of cluster
      analysis these maps include inside aggregated information about standardized
      ratio value, expression of its reliability rate. The original system has been
      tested thanks to software application and methodical procedures developed by
      author of this article in the connection with progressive information technology
      of geographical information system GIS SPANS which all allow quite easily to
      carry out the detection of another diagnoses spatial distribution within selected
      resolution and provided data. Mentioned above conclusions may be suggested as a
      basic descriptive method for the health risk assessment. Another analytical
      procedures can follow this original method in next phases. The method has brought
      essentially new view of the disease spatial distribution which has not been used
      in the Czech Republic in such a range and detail yet. There are being uncovered
      great possibilities that could in the end contribute to discovering of causal
      connections - mainly diseases with unfavourable development in time series. At
      the same time the introductory premise about spatial distribution of events to
      "skip" with the change of resolution has been confirmed.

PMID- 11243582
TI  - The mechanism of maitotoxin-induced elevation of the cytosolic free calcium level
      in rat cerebrocortical synaptosomes.
AB  - The present study was conducted to elucidate the mechanism of the maitotoxin
      (MTX)-induced increase in intrasynaptosomal free calcium level ([Ca2+]i). The MTX
      (1 ng/ml)-induced increase in [Ca2+]i was partially inhibited by the omission of
      extracellular Ca2+ (Ca2+e) or the addition of verapamil, but not by adding
      nifedipine, omega-agatoxin IVA, omega-conotoxin GVIA and omega-conotoxin MVIIC.
      An increase in [Ca2+]i in the absence of Ca2+e was sensitive to procaine, TMB-8,
      genistein and verapamil, but not to ryanodine and U-73122. These results may
      suggest that MTX increases [Ca2+]i by stimulating Ca2+ entry through voltage
      independent nonselective cation channels and Ca2+ release from stores through a
      phospholipase C-gamma1-mediated pathway in rat cerebrocortical synaptosomes.

PMID- 11243584
TI  - Does glucose tolerance affect elderly persons' balance, gait or muscle strength?
AB  - The aim of this study was to find out if there are associations between the
      deterioration of glucose tolerance and balance, gait or muscle strength among non
      institutionalised northern Finnish subjects aged 70 years or over. 79% of the
      eligible 483 subjects participated in the study (n = 379; of whom 141 were men).
      14 % (n = 19) of the men had previously diagnosed diabetes, 9% had undiagnosed
      diabetes, and 32% had impaired glucose tolerance (IGT). The corresponding figures
      for the women were 19% (n = 46), 9% (n = 21) and 35% (n = 84). The proportion of
      the female subjects with good balance tended to decrease along with the
      deterioration of the glucose tolerance status and there was a trend that
      disturbances in gait (walking speed, step length among the women) increased along
      with the deterioration of glucose tolerance. A greater proportion of the
      previously diagnosed diabetic subjects had decreased thenar (p = 0.09),
      interosseus (p = 0.00), tibialis anterior (p = 0.003), tibialis posterior (p =
      0.07) and peroneus (p = 0.03) muscle strength and decreased or missing biceps (p
      = 0.019) and quadriceps (p = 0.010) tendon reflexes. More of the subjects with
      abnormal glucose tolerance had weakening of the abdominal muscles compared to the
      persons with normal glucose tolerance (NGT) (p = 0.001). A greater proportion of
      the previously diagnosed diabetic subjects had abnormal vibration sense in the
      sternum compared to the subjects with NGT (p = 0.028) and the tendency was
      similar for undiagnosed diabetes. As a majority of the abnormal findings in this
      study were made among the previously diagnosed diabetic patients, the long
      duration of hyperglycemia probably contributes to the development of these
      disturbances. Therefore, early detection and active treatment of hyperglycemia
      might prevent or at least delay the development of signs of diabetic neuropathy
      among elderly subjects.

PMID- 11243585
TI  - Screening of TB contacts by tuberculin skin tests in a low-incidence community by
      BCG vaccination.
AB  - A 36-year-old man, an unemployed waiter, a regular patron of two bars living in a
      Czech city suffered for about a year from disorders caused probably by
      tuberculosis (TB). When hospitalised, diabetes mellitus and extensive lung TB
      were diagnosed. TB was found also at the post mortem examination when the patient
      died one week later. Screening of his contacts by tuberculin skin tests (2TU RT23
      W. Tw.80) provided data for analyzing the usefulness of tuberculin tests for
      monitoring of propagation of TB infection among BCG vaccinated population with
      high TB prevalence in the A statistically significant difference was found in
      tuberculin reactivity between 543 contacts and 232 individuals who had not
      reported contact with, the patient. A skin reaction of 12 mm and more was found
      in 55.6% contacts while only in 2.6% of those included in the second group. The
      high tuberculin reactivity was proved in the individuals exposed to massive TB
      infection. Neither BCG vaccination, nor possible previous contact with TB in the
      past seemed to influence the actual tuberculin reactivity in the group of non
      contacts. Furthermore, it is indicative of the fact that unknown TB sources are
      rare among the Czech population. The high tuberculin reactivity is suggestive of
      a fresh infection and justifies the tuberculin testing and the application of
      chemoprophylaxis.

PMID- 11243586
TI  - The future of chronic diseases.
AB  - Major chronic diseases continue to be the main health scourge of the most
      developed countries, have only recently been retreating in frequency in the
      fledgling market economies, and are becoming dominant in many populous areas of
      the developing world. The descriptive evidence from the developments of the near
      past strongly suggests that much of the control outcomes have already been
      achieved with the existent imperfect causative knowledge. The continuation of
      desirable trends in major chronic diseases in some places like Central & Eastern
      Europe, is uncertain within the intermediate time range without gaining more
      etiological clues, among which the role of medical care is worthy of
      reconsideration. Other factors can grow in importance, like obesity, which may be
      freed from the suppressive influence of cigarette smoking to trigger major mass
      pathologies, like type 2 diabetes mellitus, arterial hypertension, some cancers
      etc. The role of social underpriviledge seems recalcitrant, although the part
      played by social share of biological risk agents may diminish in response to
      educational persuasion. The remotest destinies of some chronic diseases may
      depend on the mixture of external and genetic influences ending as
      predispositions towards some ailments, antecedents of which might have protected
      their carriers from dangers of the past unfriendly environment, like obesity (or
      diabetes) against famine, or hypertension against inefficient defense reaction.
      The resulting medium-range prediction of well-being for inhabitants of more
      developed world may not be forbidding, since increasing life expectancy needs not
      be synonymous with disability, and attaining old age does not require excessive
      sacrifice, beyond reducing number smoked, or preserving decent respiratory
      volumes.

PMID- 11243587
TI  - Dietary guidelines in the Czech Republic III.: Challenge for the 3rd millennium.
AB  - In developed countries, dietary guidelines are more and more often used as a
      source of binding information not only in public health, food production,
      nutrition and agricultural policy, but in ecology and economy as well. In view of
      that, it is imperative to formulate such guidelines that would be supported by
      relevant population studies and correspond to the European model of WHO/CINDI
      guidelines. At the turn of the millennium, the Czech guidelines were updated in
      order that serving sizes of 5 basic food groups were brought closer to
      contemporary trends emphasizing lower protein intakes and at the same time, by
      setting limit ranges, they were able to meet specific need of people of different
      age group, sex, physiological status, physical activity, etc. The conversion of
      recommended servings to nutrients was compared with the results of the actual
      food basket of the Czech population and specific recommendations for amendments
      in proportions of individual food items in food groups and subgroups were given.
      On the basis of diet guidelines, conclusions describing tasks for the beginning
      of the third millennium were made. Besides them the most important are:
      production or health information systems with special emphasis to food intake and
      nutritional status report, policies to increase the access to vegetables and
      fruit for vulnerable groups, legislation to curb advertising high-fat energy
      dense foods to children, policy to strengthen the operational targets of
      Innocenti Declaration and to increase the number of Baby Friendly Hospitals,
      legislation regarding food control systems based on international standards,
      sustainable campaigns to promote safe healthy diet, policies to ensure
      sustainable food production.

PMID- 11243588
TI  - Prenatal diagnosis of spinal muscular atrophy in Turkish families.
AB  - Prenatal diagnosis of childhood proximal spinal muscular atrophy (SMA) is carried
      out by the detection of homozygous deletions of survival motor neuron (SMN; exons
      7 and 8) and neuronal apoptosis inhibitory protein (NAIP; exons 5 and 6) genes
      located in 5q13 chromosomal region. In Hacettepe University, Department of
      Medical Biology, 203 postnatal molecular diagnoses of SMA have been carried out
      since October 1994 and prenatal diagnosis in subsequent pregnancies to couples
      who previously had an affected child became possible. Between January 1996 and
      December 1999 totally 41 SMA families were analyzed by detecting homozygous
      deletions of SMN and NAIP genes for prenatal counseling. Fetal DNAs were obtained
      from amniotic fluid and chorionic villus samples. 8/41 (20%) fetal samples were
      found to be affected and these pregnancies were terminated. It was interesting to
      find that 2 fetuses had only SMN deletions, however their affected siblings had
      both SMN and NAIP gene deletions.

PMID- 11243589
TI  - Sensitivity of Borrelia burgdorferi strains isolated in the Czech Republic.
AB  - We tested in vitro susceptibility of 5 strains of Borrelia burgdorferi sensu
      lato, isolated from patients in the Czech Republic, to penicillin G, ceftriaxone,
      cefotaxime, doxycycline and amoxycillin combined with clavulanic acid by broth
      macrodilution method on BSK medium. Results confirmed high efficacy of the tested
      drugs, particularly on B. afzelii and B. burgdorferi sensu stricto. A strain of
      B. garinii, isolated from cerebrospinal fluid, required a longer period of
      antibiotic activity before inhibitory effects were achieved. Penicillin G was
      effective only in higher concentrations, attainable by i. v. application.
      Ceftriaxone had the strongest borreliacidal activity.

PMID- 11243590
TI  - Serum matrix-degrading enzymes in rats intoxicated with selenium.
AB  - The effect of poisoning doses of selenium on serum matrix-degrading enzymes
      activity was investigated in rats intoxicated with selenium. Fifteen animals were
      receiving orally sodium selenite in a daily dose of 300 microg/kg body weight.
      Intoxication with selenium was carried out for 10 weeks. The present study
      revealed significant increase in activities of enzymes involved in the connective
      tissue matrix metabolism i.e. beta-glucuronidase, N-acetyl-beta-glucosaminidase,
      elastase and collagen peptidase. There was no change in the cathepsin activity.
      The relative enzyme activities calculated over protein level resulted in higher
      values than those found in direct measurements. Serum enzyme activity was
      increased most for elastase (about 31%) and N-acetyl-beta-glucosaminidase (about
      33%) based on activity per gram of protein. The current data indicate that
      lysosomes are target organelles for selenium toxicity. Generalized increase in
      lysosomal enzymes activity contributes to the altered metabolism of the
      connective tissue in selenium-intoxicated animals. The mechanisms that lead to
      the increase of lysosomal enzymes activity in rats receiving poisoning doses of
      selenium could be related to biochemical disturbances caused by selenium
      toxicity.

PMID- 11243591
TI  - Seroconversion rates of two different doses of hepatitis B vaccine in Turkish
      haemodialysis patients.
AB  - Seroconversion rates of hepatitis B vaccination with increasing antigen doses, in
      77 haemodialysis (HD) patients were studied in randomly divided two groups. The
      first group received the standard 20 microg recombinant HBsAg (rHBsAg) dose, and
      the second group 40 microg at the 0, 1st and 2nd months of HD. At the end of the
      study, there were no statistically significant differences between the two groups
      in the response rates of protective antibody, but the response was always higher
      in the second group. On the other hand, strong positive antibody response (> or =
      100 mlU/ml) according to dates of each dose were as 7.4%, 13.1%, 28.9% and 42.2%
      in the first group and 50.0%, 50.0%, 60.0% and 52.9% in the second group
      respectively, and there were statistically significant differences between the
      two groups in the first three months. We concluded that vaccination with higher
      antigen doses resulted in a stronger antibody response in the early period in our
      HD patients. No HBV infection was observed in these two groups in the study
      period.

PMID- 11243592
TI  - Reference values of ventilatory variables for healthy adolescents aged 15-19
      years.
AB  - The main goal of this investigation was the formation of the reference values of
      ventilatory variables for group of adolescents of both sexes at the age between
      15 and 19 years, what was done for the first time for the region of Vojvodina.
      These values are important in evaluation of respiratory data obtained from
      patients in the everyday routine examinations. The investigation was carried out
      on 1151 healthy school children--nonsmokers having the same ethnic origin from
      the region of Vojvodina. There were 567 males and 584 female participants.
      Vitalograph dry spirometer (Vitalograph Ltd, Moreton House, Buckingham, England)
      was used in these examinations. The whole procedure was explained and
      demonstrated to the participants and best results of their consecutive attempts
      were taken for further statistical analysis, ie., for calculations of the mean,
      SD, SEM, coefficient of variation and linear regression. All tests were performed
      in the morning hours between 8-12 a.m. The results obtained served for
      calculating the reference values of forced vital capacity (FVC), volume expired
      in first second of FVC (FEV1.0) and forced midexpiratory flow (FMF). A positive
      correlation between the respiratory variables and the body height values was
      found in all groups of participants. The equations of the linear regression
      related to the ventilatory variables and the height (in 5 cm intervals) were
      formed separately for both genders. Analysis of the data shows significant
      differences of the values for all respiratory variables between males and
      females, which increased with the increasing height of the person. The values for
      the male group were always higher. In taller volunteers the difference between
      the sexes becomes even statistically significant, what points that it is
      necessary to calculate the equations for each gender separately.

PMID- 11243593
TI  - Civilization as a threat to human health?
AB  - Civilization can be defined as the distinctly human attributes and attainments of
      a particular society. In general, the development of civilization is viewed as a
      positive step for the well-being of the human species, leading to an increased
      duration and quality of human life. The accelerated progress of civilization
      (mainly industrialization, urbanization and nutrition) has lead to new
      possibilities for adverse effects on human health. A collection of problems
      referred to as 'civilization diseases' has become the subject of serious concern
      but review of available data indicates that this concept appears to add very
      little to our understanding of modern environmental influences on human health.
      Important limitations in the continued use of this term are its non-specificity,
      the lack of a unifying scientific foundation, and provision of virtually no
      direction for remediation of these diseases or for future research. In addition,
      the use of this term has been localized to primarily post-socialist European
      countries. In view of these limitations, it seems more productive for scientists,
      in all parts of the world, to embrace the discipline of environmental health
      science and to discontinue use of the term "civilization diseases".

PMID- 11243594
TI  - Cellular interactions in vascular growth and differentiation.
AB  - In nature, mammalian cells do not exist in isolation, but rather are involved in
      interactions with other cells and matrix. In this review, several aspects of
      cellular interactions that are important in vascular growth and development will
      be highlighted. The cardiovascular system is the earliest to develop in the
      embryo. A number of growth factors and their receptors mediate the complex stages
      of migration, assembly, organization, and stabilization of developing vessels. In
      the adult organism, normal angiogenesis is restricted primarily to tissue growth
      (such as muscle and fat), the wound healing process and the female reproductive
      system. However, pathological angiogenesis, such as with tumor growth, diabetic
      retinopathy, and arthritis, is of great concern. The identification and/or
      development of exogenous and endogenous angiogenesis inhibitors has added to the
      understanding of these pathological processes. In addition to cellular
      interactions via ligands and receptors, cells also interact directly through
      physical contacts. These interactions facilitate anchorage, communication, and
      permeability. Since vessels serve as non-leaky conduits for blood flow as well as
      interfaces for molecular diffusion, the physical interactions between the cells
      that make up vessels must be specific for the function at hand. Permeability is a
      specialized function of vessels and is mediated by intracellular mechanisms and
      intercellular interactions. Cells also interact with the surrounding
      extracellular matrix. Integrin-matrix interaction is a two-way exchange critical
      for angiogenesis. Matrix metalloproteinases and tissue inhibitors of matrix
      metalloproteinases play major roles in embryonic remodeling, adult injury, and
      pathological conditions. Several experimental model systems have been useful in
      our understanding of cellular interactions. These in vitro models incorporate
      heterotypic cell-cell interactions and/or allow cell-matrix interactions to
      occur.

PMID- 11243595
TI  - Regulation of molecular motor proteins.
AB  - Motor proteins in the kinesin, dynein, and myosin superfamilies are tightly
      regulated to perform multiple functions in the cell requiring force generation.
      Although motor proteins within families are diverse in sequence and structure,
      there are general mechanisms by which they are regulated. We first discuss the
      regulation of the subset of kinesin family members for which such information
      exists, and then address general mechanisms of kinesin family regulation. We
      review what is known about the regulation of axonemal and cytoplasmic dyneins.
      Recent work on cytoplasmic dynein has revealed the existence of multiple isoforms
      for each dynein chain, making the study of dynein regulation more complicated
      than previously realized. Finally, we discuss the regulation of myosins known to
      be involved in membrane trafficking. Myosins and kinesins may be evolutionarily
      related, and there are common themes of regulation between these two classes of
      motors.

PMID- 11243596
TI  - Current status of flow cytometry in cell and molecular biology.
AB  - This review summarizes recent developments in flow cytometry (FC). It gives an
      overview of techniques currently available, in terms of apparatus and sample
      handling, a guide to evaluating applications, an overview of dyes and staining
      methods, an introduction to internet resources, and a broad listing of classic
      references and reviews in various fields of interest, as well as some recent
      interesting articles.

PMID- 11243597
TI  - Genetic and epigenetic changes in stomach cancer.
AB  - Genetic and epigenetic alterations of multiple cancer-related genes and molecules
      are implicated in the development and progression of human gastric carcinomas.
      Reactivation of telomerase, inactivation of p53 tumor suppressor gene,
      overexpression of cyclin E, and reduced expression of p27 KIP1 by disorganized
      degradation in proteasome are common events of both well-differentiated and
      poorly differentiated gastric adenocarcinomas. Inactivation of hMLH1 mismatch
      repair gene by CpG hypermethylation resulting in microsatellite instability,
      amplification of c-erbB2 oncogene, inactivation of APC tumor suppressor gene, and
      K-ras mutations are preferentially associated with well-differentiated gastric
      cancer. Conversely, reduction or loss of E-cadherin and catenins by both mutation
      and CpG hypermethylation and K-sam and c-met oncogene amplification are necessary
      for the development and progression of poorly differentiated or scirrhous gastric
      carcinomas. Interaction between cancer cells expressing c-met and hepatocyte
      growth factor from stromal cells is implicated in morphogenesis of gastric
      cancer.

PMID- 11243598
TI  - Molecular motors and their functions in plants.
AB  - Molecular motors that hydrolyze ATP and use the derived energy to generate force
      are involved in a variety of diverse cellular functions. Genetic, biochemical,
      and cellular localization data have implicated motors in a variety of functions
      such as vesicle and organelle transport, cytoskeleton dynamics, morphogenesis,
      polarized growth, cell movements, spindle formation, chromosome movement, nuclear
      fusion, and signal transduction. In non-plant systems three families of molecular
      motors (kinesins, dyneins, and myosins) have been well characterized. These
      motors use microtubules (in the case of kinesines and dyneins) or actin filaments
      (in the case of myosins) as tracks to transport cargo materials intracellularly.
      During the last decade tremendous progress has been made in understanding the
      structure and function of various motors in animals. These studies are yielding
      interesting insights into the functions of molecular motors and the origin of
      different families of motors. Furthermore, the paradigm that motors bind cargo
      and move along cytoskeletal tracks does not explain the functions of some of the
      motors. Relatively little is known about the molecular motors and their roles in
      plants. In recent years, by using biochemical, cell biological, molecular, and
      genetic approaches a few molecular motors have been isolated and characterized
      from plants. These studies indicate that some of the motors in plants have novel
      features and regulatory mechanisms. The role of molecular motors in plant cell
      division, cell expansion, cytoplasmic streaming, cell-to-cell communication,
      membrane trafficking, and morphogenesis is beginning to be understood. Analyses
      of the Arabidopsis genome sequence database (51% of genome) with conserved motor
      domains of kinesin and myosin families indicates the presence of a large number
      (about 40) of molecular motors and the functions of many of these motors remain
      to be discovered. It is likely that many more motors with novel regulatory
      mechanisms that perform plant-specific functions are yet to be discovered.
      Although the identification of motors in plants, especially in Arabidopsis, is
      progressing at a rapid pace because of the ongoing plant genome sequencing
      projects, only a few plant motors have been characterized in any detail.
      Elucidation of function and regulation of this multitude of motors in a given
      species is going to be a challenging and exciting area of research in plant cell
      biology. Structural features of some plant motors suggest calcium, through
      calmodulin, is likely to play a key role in regulating the function of both
      microtubule- and actin-based motors in plants.

PMID- 11243599
TI  - Coronary angiography and intravascular ultrasound.
AB  - Clinicians have long used the size of the lumen and the angiogram as a predictor
      of coronary events. However, cardiovascular disease is not a disease of the lumen
      but a disease of the vessel wall. In early stages, atherosclerosis outwardly
      remodels the external elastic membrane; only late in the disease process does
      luminal narrowing occur, enabling angiographic detection. This has profound
      implications for drug therapy, because approximately 70% of patients present with
      acute myocardial infarction (MI) or sudden death, not angina as the first symptom
      of coronary disease. Intravascular ultrasound (IVUS) can provide detailed images
      of the artery and is the only technique currently available that enables
      physicians to routinely visualize coronary plaques. Due to its sensitivity in
      measuring plaque volume and content, IVUS may be a useful surrogate marker to
      evaluate the atherosclerotic process in smaller numbers of patients than required
      for conventional clinical endpoint trials.

PMID- 11243600
TI  - Introduction: utilization of surrogate markers of atherosclerosis for the
      clinical development of pharmaceutical agents.

PMID- 11243601
TI  - Laboratory surrogates for anti-atherosclerotic drug development.
AB  - Anti-atherosclerotic drug development includes the need for biochemical surrogate
      markers, because clinical parameters of efficacy are of very limited use early in
      the development process. Surrogate biochemical markers may provide a basis in
      Phase II for dose selections for Phase III trials. They may also help to improve
      selection of the most suitable population for entry to clinical endpoint trials.
      There is still a great deal of confusion as to the epidemiologic relation of
      biochemical markers and risk of coronary artery disease and whether altering
      these markers results in clinical benefit. The primary biochemical surrogate
      currently used and well accepted by regulatory agencies is low-density
      lipoprotein (LDL) cholesterol. Apolipoprotein B (apo B) is not as well accepted
      but, based on clinical trials, may be a better surrogate, because it
      simultaneously evaluates other atherogenic lipoproteins. Other potential
      surrogates include various lipid and lipoprotein subpopulations, apolipoproteins,
      procoagulants, fibrinolytics, inflammatory proteins, adhesion molecules, and
      lesion lytic enzymes. All of these parameters are involved in either the
      causation or propagation of the atherothrombotic process.

PMID- 11243602
TI  - Coronary calcium on electron beam tomography imaging as a surrogate marker of
      coronary artery disease.
AB  - Although currently recognized risk factors for coronary artery disease are
      helpful to predict the development of atherosclerosis, their ability to identify
      individual patients at risk of events is limited. Therefore, surrogate markers
      are being investigated to identify disease in its early phases in an attempt to
      decrease cardiovascular morbidity and mortality. Coronary artery calcification is
      a useful surrogate marker of coronary artery disease, and it can be visualized
      and measured noninvasively by means of electron beam tomography (EBT) imaging.
      Atherosclerosis starts to infiltrate the arterial intima layer much before
      luminal stenosis develops. Calcium is present in the large majority of mature
      atherosclerotic plaques, although, in rare cases, it may be absent. Recent
      research indicates that in selected patient subsets, coronary calcium may add
      incremental prognostic value to conventional risk factors for coronary artery
      disease and should therefore be used in association with such factors. EBT
      imaging for detection of arterial calcification is best employed in asymptomatic
      individuals at intermediate risk of coronary artery disease, symptomatic patients
      at low risk of coronary artery disease, and to track disease progression.

PMID- 11243603
TI  - Use of surrogate endpoints: a practical necessity in lipid-altering and
      antiatherosclerosis drug development.
AB  - Apparently favorable effects of antiatherosclerosis drugs as assessed by changes
      in surrogate markers of cardiovascular disease risk are frequently relied upon
      for drug approval and labeling. Surrogates must be biologically plausible and
      adequately validated but are, by definition, imperfect as predictors of ultimate
      outcome (i.e., serious morbidity and mortality). Surrogate markers utilized in
      the study of drugs for the treatment of atherosclerotic cardiovascular disease
      may be classified as laboratory/biochemical, anatomic/morphologic, and
      functional. The places for various surrogates in all three categories in the
      development of lipid altering drugs are discussed.

PMID- 11243605
TI  - Spinning out of control.

PMID- 11243604
TI  - Which tools are in your cardiac workshop? Carotid ultrasound, endothelial
      function, and magnetic resonance imaging.
AB  - There are several techniques for assessing arterial health, including carotid
      ultrasound, endothelial function, and magnetic resonance imaging. Each has pros
      and cons, but which technique is best? Quantitative intima medial thickness
      (QIMT) is safe, validated, portable, has a reference database, is inexpensive,
      and can be used in multicenter studies. Magnetic resonance imaging may be useful
      clinically, but it is still considered experimental and remains a costly
      procedure. Flow-mediated dilation (FMD) is a good surrogate measure, reflecting
      initial risk, indicating very early disease, and demonstrating rapid response to
      change. All the imaging methods require standardization of tools, operator
      training, specification of populations studied, and other considerations to be of
      use in the clinical setting.

PMID- 11243606
TI  - Clinician variability in characterizing mandible fractures.
AB  - PURPOSE: This study evaluated variability in the clinical parameters commonly
      used to characterize mandible fractures. PATIENTS AND METHODS: Inter-rater
      reliability of 18 oral and maxillofacial surgeons was assessed using radiographs
      of 22 cases of mandible fractures. Raters were asked to evaluate each case based
      on several parameters including number, location, and displacement of the
      individual fractures and severity of the composite injury. To evaluate intra
      rater reliability, selected cases were reviewed at a second session by a subgroup
      of these surgeons. Tests of concordance used to quantify measurement reliability
      included the interclass correlation coefficient and multiple-rater kappa
      statistics. RESULTS: Inter-rater agreement on the number of constituent fractures
      ranged from excellent for simpler fractures to poor for complex gunshot injuries.
      Even within raters, the range of interclass correlation for complex injuries was
      only 0.33 to 0.42 between the 2 assessments. Clinicians appeared to be better at
      delineating coronoid, condyle, ramus, and angle fractures; symphyseal and canine
      region fractures had lower inter- and intrarater agreement. Tests of concordance
      showed moderate to excellent reliability when fracture displacements were
      expressed in millimeters, but only fair reliability when displacements were
      expressed as categories. Even when the clinicians concurred on displacement
      measurements, a large overlap was observed in their categorization of these
      displacements. Despite the differences in the assessment of individual
      parameters, the high intrarater reliability coefficient (0.78) indicated that the
      individual clinicians had a high internal consistency in their assignment of
      summary severity scores. Multiple regression analysis revealed the number of
      constituent fractures, the type of fracture, and amount of fracture displacement
      (millimeters) to be significant predictors of clinician ratings of injury
      severity. CONCLUSIONS: The clinician variability underscores the difficulties
      involved in trauma description and scoring. The study identifies some sources of
      clinician variability and emphasizes the need to standardize the characterization
      of mandible fractures by using explicit guidelines.

PMID- 11243607
TI  - Treatment of carcinoma of the parotid gland: the results of a multicenter study.
AB  - PURPOSE: This study analyzed the prognostic factors for carcinoma of the parotid
      gland and the role of surgery alone or with radiotherapy in treating these
      lesions. METHODS: Forty-five patients with malignant parotid tumors were studied
      retrospectively. Patients were treated by combined surgery and radiation therapy
      between 1984 and 1995 at the Maxillo-Facial Departments of the General Hospitals
      of Bologna and Parma. Resection was conservative when possible, depending on the
      extent of the tumor. The median follow-up time was 54 months. Data regarding
      incidence, tumor stage and grade, local control, distant metastases (calculated
      with the Kaplan-Meier method), and survival were analyzed. Cox's multiple linear
      regression was used to identify patient and tumor characteristics with the
      greatest prognostic significance. RESULTS: The actuarial 5- and 8-year disease
      free survival rates were 81% and 62%, respectively. Multivariate analysis showed
      that tumor stage was a more prognostic variable than tumor grade. Residual
      microscopic disease at the excision margins was also an important prognostic
      variable. Laterocervical metastases affected 4 patients (9%), and distant
      metastases appeared in 8 patients (18%). CONCLUSIONS: Postoperative irradiation
      is indicated for patients with stage III and IV disease, patients with positive
      excision margins, and for patients with lymph node metastases.

PMID- 11243608
TI  - Fixation of bimaxillary osteotomies with resorbable plates and screws: experience
      in 20 consecutive cases.
AB  - PURPOSE: This study evaluated the potential effectiveness of resorbable plate and
      screw fixation for skeletal stabilization of simultaneously performed maxillary
      and mandibular osteotomies. PATIENTS AND METHODS: Twenty consecutive patients
      underwent simultaneous maxillary and mandibular osteotomies that were fixed using
      copolymeric poly L-lactic acid/polyglycolic acid (PLLA/PGA) plates and screws.
      Prefabricated acrylic intermediate and final splints were used as guides and then
      removed at completion of the surgery. Guidance elastics were applied at 2 weeks
      postoperatively. RESULTS: The LeFort I osteotomies included segmentalizations
      with and without bone grafts (7/20), impactions (4/20), advancements (8/20), and
      unilateral downgrafting with a bone graft (2/20)- one of which was segmental. The
      mandibular sagittal split osteotomies involved advancements (11/20), setbacks
      (5/20), and asymmetric rotation (4/20). Three patients had simultaneous
      genioplasties, which were also stabilized with resorbable fixation. All maxillae
      were fixed with four 2.0-mm L-shaped plates and screws. The mandibular rami were
      maintained with three 2.5-mm bicortical screws per side. The mandibular
      symphyseal segments were held in position with two or three 2.5 mm bicortical
      screws. All surgeries were accomplished uneventfully, and no problems in the
      immediate postoperative stability of the occlusion were encountered. Follow-up
      ranged from 12 to 25 months. CONCLUSIONS: The initial clinical findings suggest
      that this form of bone fixation is a viable alternative to standard metallic
      fixation techniques for certain maxillomandibular deformities in which excessive
      bony movements are not performed. Differences exist in both intraoperative
      application and postoperative management of masticatory function. This is
      partially a US government work. There are no restrictions on its use.

PMID- 11243609
TI  - Facial gunshot wounds: a 4-year experience.
AB  - PURPOSE: Facial gunshot wounds can result in devastating functional and aesthetic
      consequences for patients. In an attempt to evaluate the management and outcome
      in these patients, a 4-year retrospective review was undertaken of all patients
      presenting with facial gunshot wounds at a level I trauma center. PATIENTS AND
      METHODS: A total of 121 patients were identified. Medical documentation could be
      obtained on 84 of those patients. The patients' maxillofacial injuries were
      treated by the 3 participating services: plastic surgery, oral and maxillofacial
      surgery, and otorhinolaryngology. The patients ranged in age from 6 to 64 years,
      with a mean age of 27 years. RESULTS: The gunshot wounds were single in 64% of
      the cases and multiple in 36% of the cases. Overall mortality in the series was
      11%. Sixty-seven percent (56/84) of the patients suffered an injury to the
      underlying craniofacial skeleton. Seventy-five percent of these patients required
      surgical intervention. Twenty-one percent of the patients (16/75) required
      tracheostomy emergently for management of the airway. Eighteen percent (15/84) of
      these patients had an intracranial injury, with 50% of these patients requiring
      surgery. Fourteen percent of the patients in the series (12/84) had great vessel
      injuries diagnosed at the time of angiography, with 50% of these patients
      requiring surgery for treatment. CONCLUSION: Contrary to much of the published
      literature, most patients in this series required surgical intervention for
      treatment of their facial gunshot wounds. Reconstructive procedures were
      performed early in the patient's course and, when possible, addressed both the
      soft tissue and underlying bony injury in a minimum number of stages.

PMID- 11243611
TI  - Use of the preseptal transconjunctival approach in orbit reconstruction surgery.
AB  - PURPOSE: This report evaluated the advantages of the preseptal transconjunctival
      approach in reconstruction of the orbit. PATIENTS AND METHODS: Ninety-nine
      preseptal incisions were used in 80 patients for different indications (blowout
      fracture, complex zygoma fracture, enophthalmos correction, midface hypoplasia,
      secondary incision). All operative procedures were performed without an
      additional lateral canthotomy. The infraorbital rim was stabilized with
      miniplates or microplates. RESULTS: There was no ectropion or entropion in any
      patients. Complications included 1 laceration of the tarsal plate and 1 temporary
      entropion after a primary subciliary incision. The overall complication rate was
      2%. CONCLUSIONS: The preseptal transconjunctival incision without lateral
      canthotomy provides good exposure of the orbital floor and the caudal parts of
      the lateral and medial wall. This approach is preferable to a retroseptal
      approach in reconstructive orbital surgery because of minimal disturbance of the
      intraorbital connective tissue framework. The anatomic optimal dissection line
      also results in a lower complication rate.

PMID- 11243610
TI  - Ultrasound findings in HIV-positive patients with parotid gland swellings.
AB  - PURPOSE: This study aimed to determine the role that ultrasound might play in
      evaluating parotid swellings in patients with human immunodeficiency virus (HIV)
      1 disease. PATIENTS AND METHODS: The parotid glands of 13 HIV-positive patients,
      who were previously diagnosed as seropositive and who were referred because they
      had unilateral or bilateral parotid gland swellings, were examined
      sonographically. RESULTS: All patients showed multiple and varied parotid
      sonolucent areas bilaterally. These patterns reflected the presence of
      lymphoepithelial cysts, intraparotid lymphadenopathies, and parenchymal
      lymphoproliferation. CONCLUSION: Because parotid swellings can represent early
      clinical evidence of HIV disease, comprehensive gland evaluation is mandatory.
      Ultrasound offers a simple, rapid imaging technique to ascertain the nature of
      the glandular pathology.

PMID- 11243612
TI  - A histomorphometric study of the tissue reaction around hydroxyapatite implants
      irradiated after placement.
AB  - PURPOSE: The tissue reaction around hydroxyapatite (HA) implants irradiated at 3
      different time points after placement was histologically and
      histomorphometrically analyzed to further determine the relation between
      irradiation and tissue reaction. MATERIALS AND METHODS: Cylindrical high-density
      HA implants were placed in the mandibles of 48 Japanese white rabbits. The
      mandible was then irradiated with a single 15-Gy dose 5, 14, or 28 days after
      implantation. The rabbits were sacrificed on days 7, 14, 28, or 90 after
      irradiation. Nonirradiated rabbits with implants were used as controls.
      Nondecalcified specimens stained with toluidine blue were used for histologic
      analysis and histomorphometric measurements. RESULTS: In the rabbits irradiated 5
      days after implantation, the HA-bone contact occurred later than in the controls.
      The bone-implant contact surface ratio was lower than in the controls at each
      time of sacrifice because of necrosis of the newly formed bone just after
      irradiation. The HA-bone contact in rabbits irradiated 14 and 28 days after
      implantation was similar to that of the controls. Bone remodeling was suppressed
      in the rabbits in each group sacrificed 90 days after irradiation. CONCLUSIONS:
      Therapeutic irradiation shortly after implantation inhibits direct contact
      between the HA implant and the surrounding bone. Bone contact occurring before
      irradiation was minimally affected. Regardless of the interval between
      implantation and irradiation, postimplantation irradiation inevitably delays bone
      remodeling.

PMID- 11243613
TI  - Proliferation of masseter myocytes after distraction osteogenesis of the porcine
      mandible.
AB  - PURPOSE: Long-term success of distraction osteogenesis depends on the ability of
      the surrounding soft tissues to tolerate distraction forces and to adapt to the
      resulting increase in skeletal length and volume. The hypothesis tested in this
      study was that mandibular elongation by distraction induces myocyte
      proliferation. MATERIALS AND METHODS: Unilateral mandibular angle osteotomies
      were performed in 16 Yucatan minipigs. The hemimandibles were lengthened using
      semiburied distraction devices (Synthes Maxillofacial, Paoli, PA) with 0-day
      latency, 1, 2, or 4 mm/d distraction rates, and a neutral fixation period of
      twice the gap size in days. In 2 additional animals, the dissection and
      osteotomies were performed, and distraction devices were placed without
      activation (sham control). At the end of neutral fixation, tissues were taken
      from masseter muscle overlying the osteotomy and the equivalent region on the
      unoperated side (contralateral control). Proliferation of myocytes was estimated
      using immunohistochemical localization with antibodies against proliferating cell
      nuclear antigen (PCNA). RESULTS: Muscle overlying the distracted mandible showed
      6-fold more PCNA-positive myocytes (16.8% +/- 11.3%) than the contralateral
      control side (2.8% +/- 1.1%, P < .0001). In the 2 sham-control animals, there was
      a low index of PCNA-positive myocytes on both the osteotomy (2%, 5%) and the
      contralateral sides (1%, 2%). CONCLUSIONS: The results of this study suggest that
      distraction of the porcine mandible by the protocol described induces myocyte
      proliferation in the masseter muscle. A proliferative response may contribute to
      improved long-term stability of mandibular expansion by distraction osteogenesis.

PMID- 11243614
TI  - Surgical arthroscopy as the preferred treatment for internal derangements of the
      temporomandibular joint.

PMID- 11243615
TI  - Arthroscopic lysis and lavage as the preferred treatment for internal derangement
      of the temporomandibular joint.

PMID- 11243616
TI  - Mixed radiographic lesion in the anterior maxilla in a 6-year-old boy.

PMID- 11243617
TI  - Unilateral mandibular lip anesthesia as the sole presenting symptom of Burkitt's
      lymphoma: case report and review of literature.

PMID- 11243618
TI  - Mandibular arteriovenous malformation treated by transvenous coil embolization: a
      long-term follow-up with special reference to bone regeneration.

PMID- 11243619
TI  - Conservative treatment of dentigerous cysts in children: a report of 4 cases.

PMID- 11243620
TI  - Epithelioid hemangioendothelioma of the oral cavity: report of case.

PMID- 11243621
TI  - Leiomyomatous hamartoma of the tongue: case report.

PMID- 11243622
TI  - Malignant hemangiopericytoma of the head and neck: a report of 3 cases.

PMID- 11243623
TI  - Simultaneous temporomandibular joint and mandibular reconstruction in an
      immunocompromised patient with rheumatoid arthritis: a case report with 7-year
      follow-up.

PMID- 11243624
TI  - Unrecognized aspiration of a mandibular incisor.

PMID- 11243625
TI  - Technique for applying 2 miniplates for treatment of mandibular angle fractures.

PMID- 11243626
TI  - Intravital staining with methylene blue as an aid to facial nerve identification
      in parotid gland surgery.

PMID- 11243627
TI  - Proper management of pseudoaneurysm of the superficial temporal artery.

PMID- 11243629
TI  - Keeping genetics simple.

PMID- 11243628
TI  - Justification for the minor oral surgery outcome scale.

PMID- 11243630
TI  - Investigation of cytomegalovirus and human herpes viruses 6 and 7 as possible
      causative antigens in psoriasis.
AB  - Psoriasis is probably a T-cell-mediated autoimmune disease. Infectious models of
      autoimmune diseases have been proposed and in psoriasis, it has been suggested
      that there may be molecular mimicry between streptococcal antigens and epidermal
      keratins. The immunological profile of stable psoriasis plaques suggests,
      however, that viral antigens may be important. We investigated, using polymerase
      chain reaction techniques, whether DNA from either cytomegalovirus (CMV) or human
      herpes viruses (HHV) 6 and 7 is present in the skin of patients (n = 10) with
      chronic plaque psoriasis. We also investigated 29 patients for the presence of
      serum IgG to CMV. We found no evidence of CMV or HHV 7 DNA in psoriasis plaques
      although DNA for HHV 6 was detected in both involved and uninvolved skin in 1 out
      of 10 patients. There was no statistically significant increase in prior CMV
      infection, as assessed by the presence or absence of serum IgG to CMV, in
      psoriasis, compared to our local population. Although there is circumstantial
      evidence that viral antigens may be important in the pathogenesis of psoriasis we
      found no evidence to link infection with CMV or HHV 6 and 7 with subsequent
      development of chronic plaque psoriasis.

PMID- 11243631
TI  - Proliferation of T lymphocytes from atopic dermatitis skin is enhanced upon anti
      CD3, reduced upon mitogen and superantigen, and negligible upon tuberculin
      stimulation.
AB  - Knowledge about the nature of lymphocytes infiltrating atopic dermatitis skin is
      restricted to allergen-specific T cells. We investigated the proliferative
      capacities of T lymphocytes cultured in an antigen-independent way from biopsies
      of atopic dermatitis skin. When compared with peripheral blood mononuclear cells
      (PBMC) from healthy donors or atopic dermatitis patients, the skin-homing
      lymphocytes proliferated more vigorously in response to stimulation with anti-CD3
      antibodies (1 microglml), reflecting their high response capacity. When
      stimulated with phytohemagglutinin (10 microg/ml) or staphylococcal enterotoxin A
      (0.1 microg/ml) the skin-homing lymphocytes achieved significantly lower
      proliferation levels than PBMC. In contrast to normal and atopic PBMC the skin
      homing lymphocytes did not respond to tuberculin purified protein derivative (10
      microg/ml). In the mixed lymphocyte reaction the skin-homing lymphocytes did not
      stimulate autologous PBMC to proliferate. We conclude that skin-homing
      lymphocytes have more pronounced immune deviations than PBMC in patients with
      atopic dermatitis. They represent a valuable approach for further investigating
      the pathogenesis of the disease.

PMID- 11243632
TI  - Skin-identical lipids versus petrolatum in the treatment of tape-stripped and
      detergent-perturbed human skin.
AB  - The cutaneous permeability barrier is localized to the stratum corneum
      interstices and is mediated by lamellar bilayers enriched in cholesterol, free
      fatty acids and ceramides. Topically applied lipids may interfere with the skin
      barrier function and formulations containing "skin-identical lipids" have been
      suggested to facilitate normalization of damaged skin. The aim of the present
      study was to compare the ability of "skin-identical lipids" in a petrolatum-rich
      cream base and pure petrolatum to facilitate barrier repair in detergent- and
      tape-stripped-perturbed human skin. Barrier recovery and inflammation were
      instrumentally monitored for 14 days as transepidermal water loss and skin blood
      flow, using an Evaporimeter and a laser Doppler flowmeter, respectively.
      Treatment with the 2 different products gave no indication that "skin-identical
      lipids" in a cream base are more efficient than pure petrolatum at promoting
      normalization in either of the 2 experimentally perturbed areas. This finding may
      support the hypothesis that different types of skin abnormality should be treated
      according to the underlying damage.

PMID- 11243633
TI  - Tumour necrosis factor-alpha does not influence proliferation and differentiation
      of healthy and psoriatic keratinocytes in a skin-equivalent model.
AB  - Tumour necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis
      of psoriasis. Its effect on keratinocytes from healthy and psoriatic skin was
      investigated. The keratinocytes were co-cultured with healthy and psoriatic
      fibroblasts in skin equivalents and grown in a serum-free medium for 15 days. TNF
      alpha was added, or not, on day 12. The expression of differentiation and
      proliferation markers was investigated with immunohistochemistry. The epidermal
      growth rate was assessed by the percentage of Ki-67-positive nuclei in the basal
      layers of the outgrowths, which were all multilayered and orthokeratotic. The
      expression of the epidermal growth factor receptor, cytokeratin 16, involucrin
      and filaggrin displayed a hyperproliferative, regenerative pattern. No
      statistically significant differences in growth rate were found between the
      groups. These findings indicate a lack of effect of TNF-alpha on proliferation
      and differentiation in healthy and psoriatic keratinocytes. Further studies are
      warranted to elucidate the pathophysiological role of TNF-alpha in psoriasis.

PMID- 11243634
TI  - Experimental Candida albicans lesions in healthy humans: dependence on skin pH.
AB  - The addition of suspensions of Candida albicans cells under occlusion to the left
      and right forearms, buffered at 2 different pH levels (6.0 and 4.5), resulted
      after 24 h in unilateral or bilateral lesions in 14 of 15 volunteers. The
      resulting skin-surface pH was 5.7+/-0.3 and 5.1+/-0.2, respectively. The lesions
      were more pronounced on the arm with the higher pH in all 14 subjects who
      reacted. In 11 cases, reactions occurred only on the arm with the higher pH. The
      pH-induced results are not due to inhibited growth of C. albicans. They may be
      due to a pH dependence of the yeast's virulence capacity and/or a modulation of
      the host's defence ability. The use of skin-occlusive products (e.g. dressings,
      diapers and panty liners) is known to raise skin pH and is associated with skin
      infections of C. albicans. An acidic buffer incorporated in such products could
      be a preventive measure for Candida-induced skin rash.

PMID- 11243635
TI  - Is Helicobacter pylori infection associated with chronic urticaria?
AB  - There have been controversial reports of an elevated prevalence rate of
      Helicobacter pylori infection in chronic urticaria patients. Furthermore, in some
      studies remission of chronic urticaria has been reported after eradication of H.
      pylori. The aim of this investigation was to evaluate the prevalence of H. pylori
      infection among chronic urticaria patients and to study the effect of eradication
      therapy on urticaria symptoms. Chronic urticaria patients (n=235) were enrolled
      and H. pylori status was determined serologically. Thirty-five patients received
      antimicrobial triple therapy. 25% of the patients were positive for H. pylori.
      The prevalence of H. pylori infection was not significantly higher among
      urticaria patients compared with the normal Finnish population in any of the age
      groups studied. Of the successfully treated patients, 27% showed remission of
      urticaria. Our data suggest that the prevalence of H. pylori infection is not
      elevated among chronic urticaria patients and that H. pylori eradication does not
      appear to influence the course of chronic urticaria.

PMID- 11243636
TI  - Peptic ulcer and Helicobacter pylori in patients with lichen planus.
AB  - The aetiology of lichen planus is unknown, but it is often connected with
      infections. In recent years peptic ulcer disease has also been closely linked
      with an infectious agent, Helicobacter pylori. A case-control study was conducted
      in 78 patients with lichen planus to find out a previous history of peptic ulcer
      disease, using a questionnaire and a medical record review. Patients were also
      asked about family history in first- and second-degree relatives. Fifty-seven
      patients with other skin diseases were interviewed as controls. The prevalence of
      H. pylori infection in patients with lichen planus was compared to that of 39
      patients with other skin diseases and to the overall prevalence rates of H.
      pylori infection in Finland. Our findings are consistent with an approximately
      three-fold increased risk of peptic ulcer in patients with chronic/repeating
      lichen planus, when compared to the control patients (p = 0.04) and also to the
      overall peptic ulcer prevalence rates in Finland. Forty-one percent of the
      patients with chronic/repeating lichen planus had a first- or second-degree
      family member with a peptic ulcer, while the corresponding rate in the control
      group was only 12% (p=0.003). The prevalence of H. pylori infection in patients
      with chronic/repeating lichen planus and transient lichen planus was not
      significantly different from that in patients with other skin diseases.

PMID- 11243637
TI  - Health-related quality of life in patients with psoriasis and atopic dermatitis
      measured with SF-36, DLQI and a subjective measure of disease activity.
AB  - The impact of skin diseases on health-related quality of life is considerable. It
      is important to quantify the patient's perspective of the severity of their
      disease. Health-related quality of life was measured in 366 patients with skin
      diseases attending the dermatology outpatient clinic in Uppsala, Sweden, from
      November 1996 to December 1997, with 1 generic (SF-36) and 1 disease-specific
      (DLQI) health-related quality of life instrument, and a subjective measure of
      disease activity. The SF-36 mean scores were below those of the age- and gender
      matched general population in Sweden. No difference in health-related quality of
      life was found between men and women or between patients with atopic dermatitis
      and psoriatic patients. However, patients with psoriatic arthritis had
      significantly poorer health-related quality of life than both patients with
      atopic dermatitis and psoriatic patients. The estimated correlations between the
      instruments were in the expected direction and mostly significant. The results
      confirm that skin diseases have an adverse impact on patients' health-related
      quality of life.

PMID- 11243639
TI  - Increased basic fibroblast growth factor levels in serum and blister fluid from
      patients with vitiligo.
AB  - Basic fibroblast growth factor (bFGF) is a pleiotropic growth factor which has a
      high capacity for stimulating normal melanocyte proliferation and suppressing
      melanogenesis. The close and complicated relationship between bFGF, melanocyte
      proliferation and melanogenesis raises the theoretical possibility that bFGF may
      also be involved in the pathomechanism leading to vitiligo. The aim of this study
      was to compare the serum and suction blister fluid bFGF levels of vitiligo
      patients (9 females, 11 males) with those of healthy controls (3 females, 8
      males). Vitiliginous skin-blister fluid bFGF levels and serum levels were
      significantly higher in vitiligo patients compared with healthy normal controls.
      Our data indicate that bFGF might be involved in the pathogenetic chain of events
      leading to vitiligo. Further studies are needed to define the exact role of bFGF
      and various other melanocytic mitogens in this disease.

PMID- 11243638
TI  - In vivo testing of the protection provided by non-latex gloves against a 2
      hydroxyethyl methacrylate-containing acetone-based dentin-bonding product.
AB  - In dentistry, allergic contact dermatitis to acrylates and allergic contact
      urticaria to latex are important occupational hazards. There is a need to
      identify non-latex gloves which are suitable for dental work but at the same time
      provide adequate protection against acrylate monomers. In a previous study, a new
      open-chamber system was used for testing the in vivo protection of 6 different
      gloves against an acrylate-containing ethanol-based dental adhesive. A nitrile
      glove gave the best protection among the gloves suitable for dental work. In the
      present study, the test model was used to investigate the in vivo protection of 7
      non-latex gloves against a dental bonding product containing 2-hydroxyethyl
      methacrylate (2-HEMA) in an acetone/water vehicle. Eight 2-HEMA-allergic patients
      participated. Two neoprene gloves gave the best protection. The protection of the
      poorest glove was comparable to that of the positive control (no glove). The
      study produced in vivo data useful in the implementation of individual
      preventative measures against contact allergy to acrylates.

PMID- 11243640
TI  - Analysis of the CDKN2A and CDK4 genes and HLA-DR and HLA-DQ alleles in two
      Spanish familial melanoma kindreds.
AB  - Some confusion exists in the literature about which criteria should be used to
      define familial melanoma. This could explain the different reported frequencies
      of mutations in predisposing genes, mostly CDKN2A, in these patients. This study
      evaluated the human leucocyte antigen (HLA) class II genotype and the presence of
      mutations in CDKN2A and CDK4 genes in 2 families with very different clinical
      features. The family with a germinal mutation in exon 2 of CDKN2A (Gly101Try)
      presented the following clinical features: 3 first-degree affected members, 1 of
      whom had 2 melanomas, and all the melanomas appearing before 35 years of age. In
      contrast, the second family did not present any mutation in the studied genes and
      included 2 first-degree affected members diagnosed at over 45 years of age.
      Neither family showed an association with HLA genotype. Other genes are also
      involved in familial melanoma but, when the CDKN2A gene is affected, some
      clinical features seem to be uniform.

PMID- 11243641
TI  - Immunohistological distribution of stem cell factor and kit receptor in
      angiosarcoma.
AB  - Angiosarcoma is a rare neoplasm, originating in the endothelium, which has a poor
      prognosis because of a high potential for metastasis. Although little is known
      about the pathogenesis of angiosarcoma, angiogenic cytokines are suggested to
      play an important role in tumor progression in a paracrine/autocrine fashion.
      Mast cells contain several mediators or cytokines influencing vascularization. To
      clarify the role of mast cells in angiosarcoma, mast cells were counted in
      primary lesions of angiosarcoma (n=7). The results showed that the number of mast
      cells in the lesional skin of angiosarcoma (91.2+/-14.6/mm2) was significantly
      increased compared to that in normal skin (30.1+/-4.6/mm2) (p < 0.001).
      Immunohistological localization of stem cell factor, a mast cell growth factor,
      demonstrated that stem cell factor-positive cells occurred in the tumors forming
      the vascular lumen in nodular-type angiosarcoma. In macular angiosarcoma, stem
      cell factor was also detected in the tumor vascular endothelial cells.
      Infiltrating mast cells were positive for the kit receptor in both types of
      angiosarcoma. These results suggest that tumor cell-derived stem cell factor may
      play a role in the increased number of mast cells, via the kit receptor, which
      may contribute to the proliferation of tumor cells, leading to the progression of
      angiosarcoma.

PMID- 11243642
TI  - Zosteriform and disseminated lesions in cutaneous leiomyoma.

PMID- 11243643
TI  - Prurigo pigmentosa associated with diabetic ketoacidosis.

PMID- 11243644
TI  - An intensely pruritic eruption on the back occurring after stopping dieting.

PMID- 11243645
TI  - Topical tacrolimus is effective for facial lesions of psoriasis.

PMID- 11243646
TI  - An unusual location of nodular elastosis with cysts and comedones (Favre
      Racouchot's disease).

PMID- 11243647
TI  - The coexistence of amyopathic dermatomyositis and fibromyalgia.

PMID- 11243648
TI  - Serum interleukin-15 levels are not elevated in patients with stage I and II
      mycosis fungoides.

PMID- 11243649
TI  - Discoid and subacute cutaneous lupus erythematosus: detection of differences in
      peripheral lymphocyte numbers.

PMID- 11243650
TI  - Stevens-Johnson syndrome associated with bezafibrate.

PMID- 11243651
TI  - Antimalarial drugs and pruritus in patients with lupus erythematosus.

PMID- 11243652
TI  - Clinical value of fructosamine measurements in non-healthy dogs.
AB  - Ninety-three unhealthy dogs (including some with diabetes mellitus or insulinoma)
      of different ages, sex and breeds were divided into 10 groups according to their
      pathology. Serum fructosamine concentrations were determined using a commercial
      colorimetric nitroblue tetrazolium method. Diabetic dogs had the highest
      fructosamine concentrations (454.85 +/- 149.34 micromol/L). Dogs with insulinoma
      had significantly lower fructosamine concentrations (202.80 +/- 31.22
      micromol/L), similar to those with leishmaniosis (202.83 +/- 99.83 micromol/L).
      Fructosamine concentrations in non-healthy dogs, except those with diabetes
      mellitus, insulinoma or leishmaniosis, were within the reference limits
      previously reported.

PMID- 11243653
TI  - A comparison of the concentrations of C-reactive protein and alpha1-acid
      glycoprotein in the serum of young and adult dogs with acute inflammation.
AB  - The concentrations of C-reactive protein (CRP) and alpha1-acid glycoprotein (AAG)
      were evaluated in 1-, 3- and 18-month-old dogs (four of each age) that had been
      inoculated with turpentine oil. The CRP and AAG in 3-month-old and younger dogs
      subjected to surgery or inoculated with either Staphylococcus aureus or a viral
      vaccine were also evaluated. The average CRP concentration in the sera peaked 2
      days after inoculation of turpentine oil. The peak CRP concentrations in 3- and
      18-month-old dogs were significantly (p < 0.05) greater than those in 1-month-old
      dogs. The average AAG concentration in the sera peaked 4 days after inoculation
      of turpentine oil. No significant difference was found in AAG concentrations
      between any of the age groups. When experimentally inoculated with S. aureus or
      subjected to oophorohysterectomy, the CRP and AAG concentrations increased in 3
      month-old dogs, but they increased little in 1-month-old dogs. The CRP and AAG in
      dogs inoculated with the viral vaccine did not increase. In dogs with fractures
      or subjected to percutaneous gastrostomy, the CRP and AAG concentrations
      correlated with the condition of dogs.

PMID- 11243654
TI  - Tolerance to the nephrotoxic component of Narthecium ossifragum in sheep: the
      effects of repeated oral doses of plant extracts.
AB  - Young adult sheep were dosed with extracts of Narthecium ossifragum plants by the
      oral or parenteral routes and the resulting nephrotoxicity was assessed from the
      increases in the concentrations of creatinine and urea in the serum. Following
      single intraruminal or intraperitoneal doses of extracts derived from 30 g N.
      ossifragum (wet weight) per kg live weight (kg lw), serum creatinine
      concentrations increased from about 100 micromol/L to between 260 and 510
      micromol/L. The serum urea concentrations increased from about 5-8 mmol/L to
      between 11 and 66 mmol/L in individual sheep. Daily intraruminal administration
      of 5-30 g/kg lw to three sheep over a 10- or 15-day period increased creatinine
      concentrations from 100 micromol/L to 300-760 micromol/L, and urea concentrations
      from 5-8 mmol/L to 35 mmol/L. A single intraperitoneal challenge dose of 30 g/kg
      lw, delivered 7 or 12 days after the final intraruminal dose, did not lead to
      increased serum creatinine or urea concentrations, indicating that oral treatment
      had apparently resulted in an increased tolerance to the nephrotoxic principle(s)
      in N. ossifragum.

PMID- 11243655
TI  - Ultrasound-spirometry and capnography in horses: analysis of measurement
      reliability.
AB  - Ultrasound-spirometry and capnography and the evaluation of corresponding 'single
      breath diagrams for CO2' (SBD-CO2) is a relatively new, non-invasive method for
      assessing pulmonary function in horses. The relative variation and the
      reliability of observations within measurement sessions were calculated for
      expiratory tidal volume, for expired CO2 volume (%) and for the phase II and
      phase III slopes of the SBD-CO2 in horses without pulmonary disease and in horses
      suffering from differing degrees of chronic obstructive pulmonary disease. The
      coefficient of variation of expiratory tidal volume ranged from 0.23 to 0.32 and
      that of the expiratory CO2 volume from 0.19 to 0.43. The reliability of the
      measurements can be considered as good for expiratory tidal volume, and as
      excellent for expiratory CO2. Clinical status had little influence on the
      descriptive parameters or on the sample statistics of the expiratory tidal volume
      and expiratory CO2. The slopes of the SBD-CO2 curves had high variation and only
      moderate to good reliability. Clinical status had a considerable influence on the
      variation in the slopes of phase II.

PMID- 11243656
TI  - Evaluation of rat neutrophil beta-adrenergic receptors by microphysiometry.

PMID- 11243657
TI  - Preliminary observations on the concentrations of serum luteinizing hormone and
      follicle-stimulating hormone during gestation in bactrian camels (Camelus
      bactrianus).
AB  - The concentrations of luteinizing hormone (LH) and follicle-stimulating hormone
      (FSH) in the serum of the Bactrian camel (Camelus bactrianus) throughout
      pregnancy were analysed by radioimmunoassay. The samples were withdrawn at
      intervals of half a month. The serum LH concentrations varied significantly
      between 2.2+/-0.9 and 20.3+/-18.8 ng/ml during the pregnancy, with the highest
      value on the day of artificial insemination, which indicated that a preovulatory
      LH peak appeared. Thereafter, the LH concentration tended to fall, reaching a
      fairly constant low level by the eighth month of pregnancy. The serum FSH
      concentrations varied between 7.0+/-0.2 and 28.9+/-0.4 ng/ml during gestation,
      with the peak value being reached at 4.5 months, followed by a marked drop to
      7.0+/-0.2 ng/ml at 7.5 months.

PMID- 11243658
TI  - Genotyping of bovine viral diarrhoea viruses isolated from cattle in northern
      Italy.
AB  - Following the first official report of a clinically severe outbreak of bovine
      viral diarrhoea disease occurring in a farm in northern Italy, which had
      originated from the use of a live vaccine contaminated with a strain of BVD
      genotype II virus, a retrospective study on the prevalence of BVDV genotypes in
      Italy became highly relevant. For this purpose, the genotype of 78 BVDV-positive
      specimens, obtained in 1998-1999 from dairy cattle in an area near to where the
      outbreak occurred, was characterized by PCR technology. Two sets of primers,
      spanning the 5' UTR of BVDV genome, were used sequentially in a first round of RT
      PCR, performed on viral RNA extracted directly from 15 clinical samples and 63
      BVDV-infected cell-culture fluids; a second PCR assay followed to selectively
      amplify only BVDV genotype II. All the viruses under study were characterized as
      BVDV genotype I. As well as contributing to a better understanding of the
      prevalence of BVDV genotypes in the field, the results of the present study
      illustrate the possibility that novel BVDV strains can emerge in susceptible
      animals through the use of contaminated immunobiological products for bovine use.

PMID- 11243660
TI  - Concentrations of IL-6 in serum and whey from healthy and mastitic cows.
AB  - Inflammatory cytokines, such as interleukin (IL)-6, have been shown to reflect
      clinical signs in certain conditions in diseased animals. In this study, we
      quantified the IL-6 concentrations in the serum and milk whey from 94 dairy cows
      with acute clinical mastitis and 55 healthy lactating cows. The IL-6
      concentrations in serum from mastitic cows were significantly higher on the first
      day of illness compared to those of normal cows. Higher concentrations of IL-6
      were also detected in the whey from mastitic cows, whereas low concentrations of
      IL-6 were detected in both serum and whey samples from normal cows. IL-6
      concentrations in the serum taken at the onset of illness from cows that later
      required euthanasia were significantly higher than those in samples from cows
      that later recovered. These results suggest that serum IL-6 concentrations may be
      of prognostic value in identifying cows with severe mastitis.

PMID- 11243659
TI  - Caseous lymphadenitis in goats: the pathogenesis, incubation period and
      serological response after experimental infection.
AB  - Twenty goats, in two groups of 10, were injected intradermally with
      Corynebacterium pseudotuberculosis. The doses of infection were 1 x 10(5) and 5 x
      10(4) colony-forming units (cfu) for groups 1 and 2, respectively. Thereafter, a
      goat from each group was killed every 2-3 days and examined for gross and
      microscopic caseous lesions in the draining lymph nodes. Bands or zones of
      macrophages and polymorphonuclear granulocytes were observed microscopically on
      the second day of infection in both groups. Gross caseous lesions were observed
      from days 8 and 9 of infection, respectively. Positive bacterial agglutination
      test and haemolysis inhibition test titres were detected after 15-17 days and 20
      25 days of infection, respectively. These results indicated that caseous
      lymphadenitis is a subacute disease with an incubation period of 8-9 days, but
      that it is not detectable serologically until after 15 days of infection.

PMID- 11243661
TI  - Making resuscitation decisions: balancing ethics with the facts.

PMID- 11243662
TI  - Future directions in healthcare in New Zealand: my vision.

PMID- 11243663
TI  - Delay in diagnosis of anterior cruciate ligament injury in sport.
AB  - AIMS: To determine the rate and timing of diagnosis of anterior cruciate ligament
      (ACL) injuries and to identify the diagnostic features. METHODS: 70 patients
      injured in sport with isolated ACL tears, who had received or were awaiting
      reconstruction, answered a telephone questionnaire about the history of injury
      and timing of diagnosis. RESULTS: 55 (79%) presented to a doctor within 24 hours
      of their injury. Eleven (16%) reported that their ACL injury was diagnosed
      correctly at initial presentation by the first doctor they saw. 34 (49%) saw two
      doctors, and 25 (36%) saw three or more doctors before the diagnosis was made.
      The mean time to correct diagnosis was two months after the injury. Specific
      questioning revealed that at the moment of injury 54 (77%) felt that the knee had
      been disrupted, 30 (43%) sensed a snap, and 26 (37%) a pop. 41 (59%) reported
      that when correctly diagnosed, little or no advice had been given to them about
      modifying their sport. CONCLUSIONS: Despite the injured athletes presenting
      early, diagnosis was usually made late. Most often, multiple doctors were
      consulted. Even when correctly diagnosed, patients were usually not given clear
      advice about sports modification to prevent recurrent ACL instability. The
      history of injury was commonly strongly suggestive of ACL tear. Popping and
      snapping are known to be commonly associated, and a sense of knee disruption was
      even more common than either in this series. These characteristic sensations
      should be sought by doctors by specific questioning to increase diagnosis rates.

PMID- 11243664
TI  - Psychological problems in New Zealand primary health care: a report on the pilot
      phase of the Mental Health and General Practice Investigation (MaGPIe).
AB  - AIM: To carry out a pilot study in two regions in order to investigate prevalence
      of psychological problems in primary care in New Zealand. METHOD: General
      Practitioners (GPs) within two geographic regions were randomly selected. All
      adult attenders at their practice on selected days were administered a short
      questionnaire, the GHQ-12, which assesses the presence of psychological symptoms.
      The GP recorded the reasons for each consultation, and was interviewed at the end
      of each day about selected patients, to determine their opinion about the type of
      psychological problems experienced. RESULTS: Three-quarters of selected GPs (76%)
      agreed to participate. 96% of patients attending their GP agreed to complete the
      GHQ. Scores from 385 completed GHQ screening questionnaires suggested that 23.4%
      of GP patients had significant psychological symptoms. When GPs were asked about
      the main reason for consultation, they identified only 5.7% of current
      consultations as being for psychological reasons. In contrast, the GPs thought
      that 20.6% of patients described having some symptoms which were either mildly,
      moderately or completely psychological in the current consultation, and
      recognised that 17.4% of their patients had a mild, moderate or severe case of
      psychological disorder over the past twelve months. CONCLUSION: GPs identified
      one in five of their patients as having symptoms which were mildly, moderately or
      completely psychological, although psychological factors were the main reason for
      consultation in only one patient in twenty. Previous reports of very low rates of
      psychological problems among GP attenders in New Zealand have been thought to
      indicate major differences in access to health care or prevalence of common
      mental disorders within primary care services in this country. However, the
      apparently low rates of conspicuous mental disorder in New Zealand general
      practices may be better explained as an artifact of the type of questions asked.

PMID- 11243665
TI  - Saying is believing.

PMID- 11243666
TI  - Refusing emergency life-sustaining treatment.

PMID- 11243667
TI  - Doctor global.

PMID- 11243668
TI  - Adolescent sexuality.

PMID- 11243669
TI  - Smoking in Christchurch--what about inequality?

PMID- 11243670
TI  - A graduate entry medical course in New Zealand?

PMID- 11243671
TI  - Evidence based clinical guidelines: are they effective?

PMID- 11243672
TI  - ACE inhibitors for hypertension.

PMID- 11243673
TI  - Women in clinical specialities.

PMID- 11243674
TI  - Adverse medical events in hospitals.

PMID- 11243675
TI  - Informed consent.

PMID- 11243676
TI  - Necrotizing fasciitis and non steroidal anti-inflammatory drugs: a case series
      and review of the literature.
AB  - AIMS: To assess two years experience of necrotizing fasciitis in the Department
      of Intensive Care Medicine (DICM), Middlemore Hospital, and to investigate a
      possible link with non steroidal antiinflammatory drugs (NSAID's). METHODS: A
      retrospective chart review of patients with soft tissue infections admitted to
      the DICM between January 1998 and December 1999. RESULTS: There were 24 cases of
      soft tissue infection, of which thirteen had necrotizing fasciitis. In the latter
      group, nine were diabetics, and three had elevated glycosylated haemoglobin.
      Seven were obese and twelve had two or more comorbities. Five were taking
      NSAID's. Wound swabs and/or tissue biopsies were positive in eleven patients, but
      only three had positive blood cultures. Mortality was 6/13 (46%). The seven
      survivors had a mean of 5.7 operations and a mean hospital stay of 39 days.
      CONCLUSIONS: The literature contains scattered anecdotal case reports linking
      NSAID's and necrotizing fasciitis. Plausible biological mechanisms exist to
      explain how these drugs might predispose to serious infection and how they may
      mask signs and symptoms, therefore delaying diagnosis. In this series, less than
      half the patients were taking NSAID'S Diabetes and other co-morbidities were
      frequently found. The role of NSAIDS remains unclear.

PMID- 11243679
TI  - Inductive inference and experimental designs: The CONSORT and QUOROM statements.

PMID- 11243677
TI  - The work-related fatal injury study: numbers, rates and trends of work-related
      fatal injuries in New Zealand 1985-1994.
AB  - AIMS: To determine the number and rates of work-related fatal injuries by
      employment status, occupation, industry, age and gender in New Zealand 1985-1994.
      METHODS: Potential cases of work-related injury deaths of persons aged 15-84
      years were identified from the national electronic mortality data files. Main
      exclusions were deaths due to suicide and deaths due to motor vehicle crashes.
      The circumstances of the deaths of each fatal incident meeting inclusion criteria
      were then reviewed directly from coronial files to determine work-relatedness.
      RESULTS: The rate of work-related fatal injury in New Zealand was 5.03/100000
      workers per year for the study period. There was a significant decline in crude
      rate over the study period. However, this was in substantial part accounted for
      by changes in occupation and industry mix. Older workers, male workers, self
      employed workers, and particular occupational groups, all had substantially
      elevated rates. Agricultural and helicopter pilots, forestry workers and fishery
      workers had the highest rates. Farmers, forestry workers, and fishery workers
      also had high numbers of deaths, together accounting for nearly 40% of all
      deaths. CONCLUSIONS: This study has demonstrated that work-related fatal injury
      remains a pressing problem for New Zealand. Several areas in urgent need of
      prevention efforts were highlighted.

PMID- 11243680
TI  - Salmonella pathogenesis and immunity: we need effective multivalent vaccines.

PMID- 11243681
TI  - Equine influenza vaccine performance: still learning lessons from the field.

PMID- 11243682
TI  - Veterinary interest in dairy sciences.

PMID- 11243683
TI  - Diversity among bovine pestiviruses.
AB  - Bovine viral diarrhoea virus (BVDV) isolates are characterized by an important
      genetic, antigenic and pathogenic diversity. The emergence of new hypervirulent
      BVDV strains in North America has provided clear evidence of pathogenic
      differences between BVDV strains. The origin of BVDV diversity is related to high
      mutation rate occurring in RNA viruses but the consequences of mutations
      obviously depend on the genes which are involved. Mutations in genes encoding for
      structural proteins of immunological importance may have practical implications.
      Knowledge of BVDV diversity is important for understanding the wide variety of
      pathogenesis of diseases caused by the virus, for monitoring the epidemiology of
      the different types and for the design of optimum laboratory tests and vaccines.
      This review focuses on the origin and consequences of BVDV diversity with regard
      to pathogenesis, biotypes, and antigenic and genetic variations.

PMID- 11243684
TI  - Epidural analgesia in the dog and cat.
AB  - SUMMARY: A brief outline of the history of epidural analgesia is followed by a
      review of the anatomy of the epidural space with particular reference to epidural
      block. The technique of epidural injection in the dog is described as are the
      indications for the technique. These include the provision of anaesthesia for
      such procedures as orthopaedic surgery of the hind limb and caesarian section.
      The cardiovascular effects of epidural block are discussed and suggestions are
      made for the prevention of hypotension. The various drugs and their combinations
      which may be used for epidural administration are outlined. The commonest used
      local anaesthetic agents are bupivacaine and lidocaine. Epidural administration
      of opioid drugs is a relatively new technique which is used to provide intra- and
      post-operative analgesia. Morphine is the drug of choice for this indication. The
      use of other classes of drugs, such as the alpha 2 agonists and ketamine, are
      also considered. A variety of side-effects, contra-indications and complications
      are described together with methods for reducing their incidence and effects.

PMID- 11243685
TI  - Salmonella: immune responses and vaccines.
AB  - Salmonella infections are a serious medical and veterinary problem world-wide and
      cause concern in the food industry. Vaccination is an effective tool for the
      prevention of Salmonella infections. Host resistance to Salmonella relies
      initially on the production of inflammatory cytokines leading to the infiltration
      of activated inflammatory cells in the tissues. Thereafter T- and B-cell
      dependent specific immunity develops allowing the clearance of Salmonella
      microorganisms from the tissues and the establishment of long-lasting acquired
      immunity to re-infection. The increased resistance that develops after primary
      infection/ vaccination requires T-cells cytokines such as IFNgamma TNFalpha and
      IL12 in addition to opsonising antibody. However for reasons that are not fully
      understood seroconversion and/or the presence of detectable T-cell memory do not
      always correlate with the development of acquired resistance to infection.Whole
      cell killed vaccines and subunit vaccines are used in the prevention of
      Salmonella infection in animals and in humans with variable results. A number of
      early live Salmonella vaccines derived empirically by chemical or u.v.
      mutagenesis proved to be immunogenic and protective and are still in use despite
      the need for repeated parenteral administration. Recent progress in the knowledge
      of the genetics of Salmonella virulence and modern recombinant DNA technology
      offers the possibility to introduce multiple defined attenuating and irreversible
      mutations into the bacterial genome. This has recently allowed the development of
      Salmonella strains devoid of significant side effects but still capable of
      inducing solid immunity after single oral administration. Live attenuated
      Salmonella vaccines have been used for the expression of heterologous
      antigens/proteins that can be successfully delivered to the immune system.
      Furthermore Salmonella can transfer plasmids encoding foreign antigens under the
      control of eukaryotic promoters (DNA vaccines) to antigen-presenting cells
      resulting in targeted delivery of DNA vaccines to these cells. Despite the great
      recent advances in the development of Salmonella vaccines a large proportion of
      the work has been conducted in laboratory rodents and more research in other
      animal species is required.

PMID- 11243686
TI  - Pathophysiological effects of low dietary phosphorus in pigs.
AB  - SUMMARY: The homeostasis of inorganic phosphate (P(i)) is regulated by
      parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25(OH)(2)D), and P(i)itself
      in the intestine, kidney, and bone in all the mammalian species studied.
      Determinations of the serum concentrations of PTH, 1,25(OH)(2)D and osteocalcin
      were done in 82 southern Romanian Landrace pigs originating from three herds with
      dietary P(i)deficiency. Serum P(i)concentrations were negatively correlated with
      those of 1,25(OH)(2)D. In lactating animals and sucklings, the linear
      relationships between P(i)and 1,25(OH)(2)D were not present. Serum
      P(i)concentrations were positively correlated with those of PTH. In lactating
      animals and young pigs, the linear relationships between P(i)and PTH were not
      evident. PTH and 1,25(OH)(2)D concentrations were negatively correlated. The
      serum concentrations of 1,25(OH)(2)D and osteocalcin were positively correlated.
      Milk P(i)concentrations ranging from 3.10 to 7.49 mmol/L were correlated
      positively with urinary P(i)concentrations ranging from 0.26 to 11.37 mmol/L. In
      conclusion, similarly to other species, P(i)homeostasis is achieved in pigs by
      feedback mechanisms between P(i), PTH and 1,25(OH)(2)D and osteocalcin production
      is induced by 1,25(OH)(2)D. The effect of lactation on P(i)homeostasis remains to
      be explored.

PMID- 11243687
TI  - Field studies on equine influenza vaccination regimes in thoroughbred foals and
      yearlings.
AB  - SUMMARY: The purpose of these studies was to examine the response of Thoroughbred
      foals and yearlings to different influenza vaccines and vaccination regimes. The
      horses' antibody levels against haemagglutinin, an established correlate of
      protection were measured by haemagglutination inhibition. The first study
      investigated the extent to which maternal antibodies interfered with the humoral
      response to a subunit vaccine. The findings suggest that repeat vaccination in
      the face of maternal antibodies may induce tolerance as defined by serological
      testing. The second study compared the immune response elicited by a subunit
      immune stimulating complex (ISCOM) vaccine, an inactivated whole virus vaccine
      and the same product containing equine herpesviruses and equine reoviruses in
      addition to equine influenza virus. The monovalent vaccine induced a
      significantly better response than the ISCOM or the multivalent vaccine. The
      final study demonstrated that the inclusion of an additional booster vaccination,
      between the second and third vaccination recommended by the vaccine manufacturers
      and required under the rules of racing in certain countries, is of benefit to
      young horses. Since these studies were performed, several of the vaccines have
      been updated with more recent virus strains in line with WHO/OIE recommendations.
      However, the general principles investigated in the studies remain relevant to
      these vaccines.

PMID- 11243688
TI  - The effect of feeding grass silage in early pregnancy on claw health during first
      lactation.
AB  - Two groups of eight Holstein-Friesian heifers were fed either a grass-silage
      based diet (S) or one based on meadow hay supplemented with 1.8 kg/day barley
      concentrate mix (H) during cubicle housing as young stock (and in early
      pregnancy). Lameness and claw lesion development were monitored from
      approximately four weeks before until 20 weeks after first calving. No
      significant difference was found between S and H for claw conformation or horn
      growth and wear. Both groups showed net wear immediately after calving. The
      prevalence of poor locomotion and the extent of lesion development 20 weeks after
      calving (when they were highest) were significantly (P< 0.05) higher in S than H.
      It was concluded that feeding grass silage to young stock may deleteriously
      affect subsequent claw health and that this risk factor requires further study.

PMID- 11243689
TI  - Glycerol hyperhydration in resting horses.
AB  - SUMMARY: To determine whether administration of glycerol-containing solutions
      induces a state of transient hyperhydration in resting euhydrated horses, changes
      in plasma and urine constituents were measured in four horses for 1 h before and
      5 h after nasogastric administration of each of four treatments (Experiment 1).
      Treatments were applied in a randomized fashion and included: (1) 1.0 g.kg(
      )(1)glycerol in 8 L of water (G); (2) 8 L of water (W); (3) 8 L of 0.9% NaCl
      solution (S); and (4) 1.0 g.kg(-)(1)glycerol in 8 L of 0.9% NaCl solution (GS).
      In a subsequent study, voluntary water intake was measured hourly for 5 h after
      nasogastric administration of each treatment (Experiment 2). All treatments
      produced mild plasma volume expansion ranging from 3.2 to 5.8% in Experiment 1.
      Administration of glycerol containing solutions increased serum glycerol
      concentration approximately 100-fold and plasma osmolality (P(osm)) by
      approximately 10 mOsm/kg and resulted in a tendency towards increased renal water
      conservation despite increased osmole excretion. In contrast, W treatment
      decreased plasma and urine osmolality and was accompanied by increased urine
      production and decreased renal water conservation. Plasma and urine osmolality,
      as well as renal osmole and water excretion, were unchanged after S
      administration. In Experiment 2, horses treated with GS voluntarily drank an
      additional 5.2 +/- 0.9 L of water during the initial hour following nasogastric
      administration of 8 L of solution. Voluntary water intake with the other
      treatments was less than 1.0 L for the entire 5 h observation period.
      Collectively, the results of both experiments suggest that administration of
      glycerol in saline would produce transient hyperhydration in resting euhydrated
      horses by enhancing renal water conservation and stimulating voluntary water
      intake.

PMID- 11243690
TI  - First evidence of a trisegmented double-stranded RNA virus in canine faeces.

PMID- 11243691
TI  - Survey of maedi-visna (MV) in ethiopian highland sheep.

PMID- 11243692
TI  - The role of accuracy motivation on children's and adults' event recall.
AB  - To examine the role of accuracy motivation in event recall, 6-, 7-, and 8-year
      old children and adults were shown a short video about a conflict between two
      groups of children. Three weeks later, participants were asked a set of unbiased
      specific questions about the video. Following A. Koriat and M. Goldsmith's (1994)
      distinction of quantity- and quality-oriented memory assessments, and based on
      their model of strategic regulation of memory accuracy (1996), accuracy
      motivation was manipulated across three conditions. Participants were (a) forced
      to provide an answer to each question (low accuracy motivation), (b) initially
      instructed to withhold uncertain answers by saying "I don't know" (medium
      accuracy motivation), or (c) rewarded for every single correct answer (high
      accuracy motivation). When motivation for accuracy was high, children as young as
      6 were to withhold uncertain answers to the benefit of accuracy. The expected
      quality-quantity trade-off emerged only for peripheral items but not for the
      central items. Participants who were forced to provide an answer gave more
      correct answers but also high numbers of incorrect answers than participants who
      had the option to answer "I don't know." The results are discussed in terms of
      the underlying model as well as in terms of forensic interviewing.

PMID- 11243693
TI  - Factor analysis of variability measures in eight independent samples of children
      and adults.
AB  - Variability in strategy use has been measured and conceptualized in several ways.
      The present study sought to determine whether a sample of variability measures
      could be reduced to a smaller number of factors that the individual measures had
      in common. Factor analysis of five commonly used variability measures was
      performed separately on data from eight independent samples of children and
      adults. The results revealed that the variability measures could be reduced to
      one of two general types of variability: strategy diversity, which refers to the
      sheer number of strategies used, and strategy change, which refers to the number
      of trial-by-trial changes in strategy use. Support for this two-factor model of
      variability was found for all samples of children and adults. Moreover, each type
      of variability had distinctive relations with cognitive performance that varied
      with age. In general, strategy diversity was positively related to recall for
      children but not adults, whereas strategy change was negatively related to recall
      for adults but not children. Based on this evidence, three recommendations for
      researchers studying strategy variability are described.

PMID- 11243695
TI  - Children's difficulties handling dual identity.
AB  - Thirty-nine 6-year-old children participated in a longitudinal study using tasks
      that required handling of dual identity. Pre- and posttest sessions employed
      tasks involving a protagonist who was partially informed about an object or
      person; for example, he knew an item as a ball but not as a present. Children who
      judged correctly that the protagonist did not know the ball was a present
      (thereby demonstrating some understanding of the consequences of limited
      information access), often judged incorrectly (1) that he knew that there was a
      present in the box, and (2) that he would search as if fully informed.
      Intervening sessions added contextual support and tried to clarify the
      experimenter's communicative intentions in a range of ways. Despite signs of
      general improvement, the distinctive pattern of errors persisted in every case.
      These findings go beyond previous studies of children's handling of limited
      information access, and are hard to accommodate within existing accounts of
      developing understanding of the mind.

PMID- 11243694
TI  - Measures of information processing in rapid automatized naming (RAN) and their
      relation to reading.
AB  - The letters, numbers, and objects subtests of the Rapid Automatized Naming Tests
      (RAN) were given to 50 first- and second-grade students. Student performance on
      the three RAN subtests were audiotaped and subjected to postacquisition
      processing to distinguish articulation and interarticulation pause times. This
      study investigated (1) the relations between the articulation and pause durations
      associated with the 50 stimuli of each RAN subtest and (2) the relations between
      the pause and articulation latencies of the three RAN subtests and reading. For
      both first- and second-grade students, pause and articulation times for RAN
      letters and objects were not found to be reliably related, in contrast to RAN
      numbers articulation and pause durations. RAN subtest pause durations were
      differentially related to reading; however, articulation was rarely related to
      reading. The RAN letters pause time was the most robust predictor of decoding and
      reading comprehension, consistently predicting all first- and second-grade
      measures. Analysis supported the view that reading is predicted by speed of
      processing associated with letters, not general processing speed.

PMID- 11243697
TI  - Chemokine receptor desensitization in tumor-bearing mice.
AB  - We found that the murine breast cancer cell line 4T1 constitutively produced
      several chemokines capable of recruiting T cells. Additionally, supernatants from
      the tumor cell line mediated chemotaxis of T cells in a pertussis toxin-sensitive
      manner, indicating that these chemokines were functional. However, we also found
      an impaired chemotactic ability of splenic T cells in mice bearing these same
      tumors. The receptors for RANTES, MCP-1, and SLC were desensitized. Thus, the
      impaired chemotactic ability of T cells in tumor-bearing mice may explain why
      tumors that secrete chemokines grow progressively in a host.

PMID- 11243696
TI  - Interleukin (IL)-4/IL-9 and exogenous IL-16 induce IL-16 production by BEAS-2B
      cells, a bronchial epithelial cell line.
AB  - Previous studies have suggested that bronchial epithelial cells may perpetuate
      airway inflammation. We have reported that the bronchial epithelial cell line
      BEAS-2B can produce interleukin (IL)-16, a potent chemoattractant for CD4+ T
      cells. IL-16 is thought to regulate airway inflammation in asthmatics. Recent
      studies showed that IL-4 induces inflammatory cytokines in bronchial epithelial
      cells and that IL-9 is a candidate gene for development of asthma. The present
      study demonstrated that BEAS-2B cells produced specifically IL-16 by synergistic
      effects of IL-4 + IL-16, or IL-9 + IL-16, and that the synthesized IL-16 induced
      migration of CD4+ T cells. This study is a first report indicating that IL-16
      production may be maintained by an autocrine machinery by epithelial cell-derived
      IL-16 with IL-4 and IL-9 in asthma.

PMID- 11243698
TI  - HIV-1 Tat protects CD4+ Jurkat T lymphoblastoid cells from apoptosis mediated by
      TNF-related apoptosis-inducing ligand.
AB  - We have here investigated the effect of TNF-related apoptosis-inducing ligand
      (TRAIL), a new member of the TNF cytokine superfamily, on the survival of Jurkat
      lymphoblastoid cell lines stably transfected with plasmids expressing the wild
      type or mutated (Cys22) human immunodeficiency virus type 1 (HIV-1) tat gene.
      Jurkat cells transfected with wild-type tat were resistant to TRAIL-mediated
      apoptosis, while Jurkat cells mock-transfected with the control plasmid or with a
      mutated nonfunctional tat cDNA were highly susceptible to TRAIL-mediated
      apoptosis. Also, pretreatment with low concentrations (10-100 ng/ml) of
      extracellular synthetic Tat protein partially protected Jurkat cells from TRAIL
      mediated apoptosis. Taken together, these results demonstrated that endogenously
      expressed tat and, to a lesser extent, extracellular Tat block TRAIL-mediated
      apoptosis. Since it has been shown that primary lymphoid T cells purified from
      HIV-1-infected individuals are more susceptible than those purified from normal
      individuals to TRAIL-mediated apoptosis, our findings underscore a potentially
      important role of Tat in protecting HIV-1-infected cells from TRAIL-mediated
      apoptosis.

PMID- 11243700
TI  - IgD receptor-mediated signal transduction in T cells.
AB  - Upregulation of immunoglobulin D-specific receptors (IgD-R) on CD4+ T cells may
      facilitate their interaction with specific carbohydrate moieties uniquely
      associated with membrane IgD on B cells. Previous studies have shown that
      upregulation of IgD-R facilitates cognate T-B cell interactions by mediating
      bidirectional signaling resulting in increased antibody responses and clonal
      expansion of antigen-specific T cells. Murine T hybridoma cells, 7C5,
      constitutively express IgD-R, as has been confirmed by staining with biotinylated
      IgD. Earlier studies have shown that inhibitors of protein tyrosine kinase (PTK)
      completely prevented upregulation of IgD-R in response to oligomeric IgD,
      suggesting that cross-linking of IgD-R may induce signal transduction and
      functional consequences through one or more PTK activation pathways, leading to
      upregulation of IgD-R. In the present study we show that cross-linking of IgD-R
      by oligomeric IgD indeed results in (a) T cell activation as seen by tyrosine
      phosphorylation of several intracellular proteins, (b) tyrosine phosphorylation
      of p56 Lck and PLC-gamma in 7C5 T hybridoma cells, and (c) phosphorylation of an
      approximately 29-kDa band that exhibits strong affinity for IgD. We analyzed
      tyrosine phosphorylation of p56 Lck and PLC-gamma in BALB/c splenic T cells that
      were exposed to oligomeric IgD both in vivo and in vitro. In vitro cross-linking
      as well as in vivo followed by in vitro cross-linking of IgD-R resulted in
      enhanced phosphorylation of p56 Lck and moderate tyrosine phosphorylation of PLC
      gamma. These results suggest that interactions between IgD-R and IgD mediate
      signal transduction and support our previous findings that IgD-R+ T cells enhance
      cognate T cell-B cell interactions and antibody production.

PMID- 11243699
TI  - The affinity/avidity and length of exposure to the deleting ligand determine
      dependence on CD28 for the efficient deletion of self-specific CD4+CD8+
      thymocytes.
AB  - Whether the CD28/B7 signaling pathway is essential for the negative selection of
      immature CD4+CD8+ (DP) thymocytes expressing self-specific alphabeta TCRs is a
      controversial issue. In this study we examined the role of CD28 in the deletion
      of thymocytes that express either the H-Y or the 2C transgenic TCR. In H-2(b)
      male mice that expressed the H-Y TCR, negative selection of DP H-Y TCR+
      thymocytes occurred very efficiently and this deletion was unaffected by the
      CD28(-/-) mutation. In H-2(b) 2C mice, where the deletion of DP 2C TCR+
      thymocytes occurred less efficiently, the CD28(-/-) mutation led to a higher
      recovery of DP thymocytes. Using an in vitro deletion assay, a requirement for
      the CD28 signaling pathway in the deletion of DP H-Y TCR+ thymocytes was evident
      at low, but not high, densities of the antigenic ligand. Similar results were
      also observed in an in vivo assay for the deletion of these thymocytes.
      Intraperitoneal administration of an anti-CD3epsilon mAb led to the intrathymic
      deletion of DP H-Y TCR+ thymocytes in a CD28-dependent manner at the 24-h time
      point. However, the CD28 dependence was less evident at the 40-h time point.
      These results indicate that the dependence on CD28 for the efficient deletion of
      self-specific thymocytes is determined by the concentration, affinity/avidity,
      and length of exposure to the deleting ligand.

PMID- 11243701
TI  - Cross-talk between RANKL and FRP-1/CD98 Systems: RANKL-mediated
      osteoclastogenesis is suppressed by an inhibitory anti-CD98 heavy chain mAb and
      CD98-mediated osteoclastogenesis is suppressed by osteoclastogenesis inhibitory
      factor.
AB  - The two pathways to osteoclastogenesis, RANKL-mediated and CD98-mediated
      osteoclastogenesis, have recently been reported. RANKL, OCIF, and TIMP-3 mRNAs
      are not found in monocytes freshly isolated or incubated with anti-FRP-1/CD98hc
      antibody. RANK, TACE, and M-CSF mRNAs can be detected in these cells.
      Interestingly, the expressed amount of RANK mRNA increases by cultivation of
      monocytes with anti-CD98hc antibody and maximal expression is observed in
      osteoclast-like cells. CD98-mediated cell aggregation and multinucleated giant
      cell formation are blocked by OCIF. OCIF also suppressed the CD98-mediated
      induction of Sp1 and c-src mRNAs in monocytes. Soluble RANK shows no effect on
      CD98-mediated cell aggregation and multinucleated giant cell formation. When
      blood monocytes were incubated with RANKL and M-CSF, c-src and Sp1 mRNAs were
      first found in blood monocytes incubated with these cytokines for 7 days. On the
      contrary, c-src mRNA could be detected 3 h after treatment of blood monocytes
      with anti-CD98hc mAb. LAT-1 mRNA was not found, and the expression levels of
      Y(+)LAT-1 and Y(+)LAT-2 mRNAs were not changed in monocytes stimulated without or
      with anti-CD98hc mAb or RANKL and M-CSF. An inhibitory mAb directed against
      CD98hc, HBJ 127, shows a suppressive effect on RANKL-mediated cell aggregation
      and cell fusion. Thus, there is cross-talk between these two pathways.

PMID- 11243702
TI  - Cytokine dependency of human B cell cycle progression elicited by ligands which
      coengage BCR and the CD21/CD19/CD81 costimulatory complex.
AB  - Coengagement of BCR and the C3dg binding CD21/CD19/CD81 costimulatory complex can
      profoundly reduce the BCR binding threshold for eliciting B cell S phase entry,
      provided cytokine is present. IL-4 is substantially better than IL-2, IL-13, and
      TNF-alpha at exhibiting synergy with BCR:CD21 coengaging ligand (anti-IgM:anti
      CD21:dextran) in promoting B cell DNA synthesis. Synergy between IL-4 and anti
      IgM:anti-CD21:dextran (a) is not explained by the viability-promoting function of
      IL-4, (b) occurs when the anti-CD21 moiety engages either C3dg binding or non
      C3dg binding domains, (c) does not reflect reversal of FcgammaRII-mediated
      negative regulation, and (d) involves differing temporal requirements for BCR and
      IL-4R signal transduction during the activation process. The IL-4R signaling
      pathway appears to synergize directly with the BCR:CD21 signaling pathway(s) in
      promoting the progression of resting B cells past an early G1 checkpoint, as well
      as to promote independently the progression of activated B cells past a later G1
      to S checkpoint.

PMID- 11243703
TI  - Phospholipids reacylation and palmitoylcoa control tumour necrosis factor-alpha
      sensitivity.
AB  - From the hypothesis that in TNF-alpha-resistant cells the activity of
      mitochondrial phospholipase A2 could be reversed by a lysophospholipid
      acyltransferase, we report that the mitochondrial reacylation of
      phosphatidylcholine as phosphatidylethanolamine was considerably higher in C6
      (TNF-alpha-resistant) than in WEHI-164 (TNF-alpha-sensitive) cells. TNF-alpha did
      not modify the phospholipids' reacylation in C6, while in WEHI-164 it was
      increased several-fold. These results suggest that TNF-alpha is not sufficient to
      restore the barrier permeability in sensitive cells, but may be enough to explain
      the absence of permeability change in resistant cells. AcylCoA esters, depending
      on whether the acyl group is unsaturated or saturated (palmitic acid), could
      control membrane permeability either by participating in the reacylation of
      phospholipids or keeping the pore in a closed state. The analysis of the
      endogenous acylCoA ester pools of both cell lines show that the amount of
      palmitoylCoA is higher in resistant than sensitive cell lines. TNF-alpha
      treatment does not change these results.

PMID- 11243704
TI  - Interferon-beta induces the development of type 2 dendritic cells.
AB  - Suppression of interleukin 12 (IL-12) production by dendritic cells (DCs) has
      been hypothesized to be a principal mechanism underlying the biological action of
      interferon (IFN)-beta used for treatment of multiple sclerosis (MS), a chronic
      inflammatory disease of the central nervous system with possible autoimmune
      origin. How IFN-beta interacts with DCs to inhibit IL-12 production remains
      unclear. In this study, we found that DCs derived from human blood monocytes,
      upon culture in the presence of IFN-beta with granulocyte-macrophage colony-
      stimulating factor (GM-CSF) and IL-4, differentiated into a population expressing
      CD14- CD1a- HLA-DR+. This population expressed CD123 (IL-3Ralpha). IFN-beta dose
      dependently increased IL-3Ralpha+ DCs and decreased CD1a+ DCs. After 7 days'
      culture with IFN-beta at a concentration of 10 000 U/ml, more than 40% of DCs
      expressed IL-3Ralpha. IFN-beta, together with GM-CSF and IL-4, also induced
      maturation of IL-3Ralpha-expressing cells, as reflected by upregulation of HLA-DR
      and of the costimulatory molecules CD40, CD80 and CD86. In contrast to control
      DCs, IFN-beta-treated DCs produced predominantly IL-10 but only low levels of IL
      12p40. Correspondingly, IFN-beta-treated DCs strongly suppressed IFN-gamma
      production but enhanced IL-10 production by allogeneic blood mononuclear cells.
      Our data suggest that IFN-beta in vitro can induce the development of DC2, which
      provide a permissive environment for Th2 differentiation. This finding represents
      a novel mechanism for action of IFN-beta in MS.

PMID- 11243705
TI  - Directly linked soluble IL-6 receptor-IL-6 fusion protein induces astrocyte
      differentiation from neuroepithelial cells via activation of STAT3.
AB  - Signals of interleukin 6 (IL-6) are transduced by binding of IL-6 to its cell
      surface receptor (IL-6R) and subsequent association of the resultant IL-6/IL-6R
      complex with gp130, the signal transducing receptor component utilized in common
      by all the IL-6 family of cytokines. A soluble form of IL-6R (sIL-6R), which
      lacks transmembrane and cytoplasmic regions, retains the ability to bind IL-6 and
      signal through gp130. We show here that a fusion protein of sIL-6R and IL-6
      without a polypeptide linker, termed FP6, induces differentiation of astrocytes
      from fetal mouse neuroepithelial cells as potently as a representative IL-6
      family cytokine, leukaemia inhibitory factor (LIF). FP6 has a potential to
      activate a transcription factor, signal transducer and activator of transcription
      3 (STAT3), and mitogen-activated protein kinases, ERK1 and ERK2, in these cells
      as does LIF. FP6 activates a promoter of the gene for an astrocytic marker, glial
      fibrillary acidic protein (GFAP), in neuroepithelial cells. This activation is
      virtually abolished by ectopic expression of a dominant-negative form of STAT3,
      or by introducing a point mutation into the STAT3 response element located in the
      GFAP promoter. These results suggest that FP6 induces astrocyte differentiation
      from neuroepithelial cells through STAT3 activation and that FP6 could be of use
      as a substitute for natural IL-6 family cytokines.

PMID- 11243706
TI  - The effects of phenolic components of tea on the production of pro- and anti
      inflammatory cytokines by human leukocytes in vitro.
AB  - Epidemiological evidence suggests protective effects of dietary flavonoids
      against cardiovascular disease. Tea provides a major source of dietary flavonoids
      in many countries and its polyphenolic components have well-recognised
      antioxidant properties. However, scavenging of free radicals may not be the sole
      mechanism by which tea-derived polyphenols exert their protective effects. This
      study investigates the effects of four major tea-derived catechins and a black
      tea extract on the production of pro- and anti-inflammatory cytokines by human
      leukocytes in vitro. Epicatechin gallate, epigallocatechin and epigallocatechin
      gallate decreased the production of interleukin 1beta and enhanced the production
      of interleukin 10, but had no effect on the production of interleukin 6 or tumour
      necrosis factor-alpha. Although these effects suggest anti-inflammatory
      properties of the tea-derived catechins, they were observed at concentrations
      which were unlikely to be achievable in plasma in vivo and are therefore unlikely
      to contribute to the protective effects of tea-derived flavonoids in inflammatory
      diseases.

PMID- 11243707
TI  - Kinetic analysis of megakaryopoiesis induced by recombinant human interleukin 11
      in myelosuppressed mice.
AB  - Recombinant human interleukin 11 (rhIL-11) has previously been shown to
      ameliorate thrombocytopenia in several animal models. To elucidate the mechanisms
      involved in rhIL-11-induced hematopoiesis, a kinetic analysis of megakaryopoiesis
      was performed in mitomycin C (MMC)-induced myelosuppressive mice. Mice
      intravenously injected with MMC (2 mg/kg) for two consecutive days from day -1
      developed severe thrombocytopenia with a nadir of platelet counts at
      24x10(4)/microl on day 12 and neutropenia. Treatment with rhIL-11 (500
      microg/kg/day) from day 1 to 21 significantly ameliorated the degree and duration
      of thrombocytopenia and enhanced the platelet recovery, and also enhanced the
      recovery from neutropenia. In MMC-treated mice, the decreases in bone marrow
      megakaryocyte progenitors and megakaryocyte counts preceded the decrease in
      platelet counts by MMC treatment. RhIL-11 induced an increase in the number of
      megakaryocyte progenitors from day 4 to 14, followed by an increase in the
      megakaryocytes by day 20. There was a ploidy shift in megakaryocytes towards
      lower ploidy cells by day 9 in myelosuppressed mice. RhIL-11 caused a shift
      towards a higher ploidy with 32 and 64N on day 4, and 32N on day 14. These
      results suggest that rhIL-11 ameliorates the thrombocytopenia via the stimulation
      of both the maturation and commitment followed by the proliferation of
      megakaryocytic cells.

PMID- 11243708
TI  - Inhibitory and enhancing effects of IFN-gamma and IL-4 on SHIV(KU) replication in
      rhesus macaque macrophages: correlation between Th2 cytokines and productive
      infection in tissue macrophages during late-stage infection.
AB  - HIV-1 is dual-tropic for CD4+ T lymphocytes and macrophages, but virus production
      in the macrophages becomes manifest only during late-stage infection, after CD4+
      T cell functions are lost, and when opportunistic pathogens begin to flourish. In
      this study, the SHIV/macaque model of HIV pathogenesis was used to assess the
      role of cytokines in regulating virus replication in the two cell types. We
      injected complete Freund's adjuvant (CFA) intradermally into SHIV(KU)-infected
      macaques, and infused Schistosoma mansoni eggs into the liver and lungs of
      others. Tissues examined from these animals demonstrated that macrophages induced
      by CFA did not support viral replication while those induced by S. mansoni eggs
      had evidence of productive infection. RT-PCR analysis showed that both Th1 (IL-2
      and IFN-gamma) and Th2 cytokines (IL-4 and IL-10) were present in the CFA lesions
      but only the Th2 cytokines were found in the S. mansoni lesions. Follow-up
      studies in macaque cell cultures showed that whereas IFN-gamma caused enhancement
      of virus replication in CD4+ T cells, it curtailed viral replication in infected
      macrophages. In contrast, IL-4 enhanced viral replication in infected
      macrophages. These studies strongly suggest that cytokines regulate the
      sequential phases of HIV replication in CD4 T cells and macrophages.

PMID- 11243710
TI  - Differential alterations in plasma colony-stimulating factor concentrations after
      coronary artery bypass graft surgery with extracorporeal circulation.
AB  - To determine whether colony-stimulating factor (CSF) might participate to the
      inflammatory response after cardiac surgery, plasma concentrations of granulocyte
      CSF (G-CSF), macrophage-CSF (M-CSF) and GM-CSF were measured in 31 patients
      undergoing coronary artery bypass graft (CABG) surgery with extracorporeal
      circulation (ECC). Plasma G-CSF and M-CSF concentrations increased after weaning
      of ECC, reached maximum value at the sixth post-operative hour, and remained
      elevated at the 24th post-operative hour. In contrast, plasma GM-CSF levels did
      not change. Plasma M-CSF, G-CSF and GM-CSF values were not different whether
      patients developed post-operative complications or not. In conclusion, M-CSF and
      G-CSF are produced after CABG surgery despite the use of high aprotinin doses in
      hope to abrogate the inflammatory response. G-CSF and M-CSF might play a role in
      the inflammatory process often observed after CABG surgery.

PMID- 11243709
TI  - Urinary cytokines for assessing inflammation in HIV-associated wasting.
AB  - The relationship between cytokines and HIV-related weight loss has not been well
      established. Unlike most cytokines that are secreted in a paracrine manner, IL-6,
      sTNFR-II, and IL-1ra are readily detected in the systemic circulation and serve
      as markers of the inflammatory response. Twenty-four-hour urine concentrations of
      these proteins are believed to provide an integrative assessment of their
      systemic levels over the preceding hours. We sought to determine whether spot
      measurements of IL-6, sTNFR-II, and IL-1ra could be related to subsequent 24 h
      concentrations and prior weight loss. Eighteen subjects with severe wasting
      (average BMI=18+/-3 kg/m2with 19+/-13 kg of weight loss) and six HIV-negative
      healthy subjects were tested. Compared to values in controls, 24-h urinary
      concentrations of the three proteins adjusted for creatinine excreted were
      elevated in 44%, 89%, and 72% of patients, respectively. Twenty-four-hour
      concentrations were highly correlated with the spot concentrations (r=0.80, 0.87,
      0.84, respectively, P<0.001). IL-1ra concentrations (24 h and spot) were
      correlated with weight loss in the previous 6 months, lifetime rate of weight
      loss and the 6 month rate of weight loss (spot: r=0.66, 0.73, 0.68, respectively,
      P< or =0.001). These data suggest that spot urinary collections can be used to
      estimate 24 h excretion rates. This strategy may be useful in assessing the
      inflammatory response in HIV-associated wasting.

PMID- 11243711
TI  - Automated behavioural analysis in animal pain studies.
AB  - The assessment of the effectiveness of analgesics is strongly based on
      observational data from behavioural tests. These tests are interesting and give a
      quantification of the effect of the drugs on the whole animal but their use is
      subject to several difficulties: (i) many results are difficult to analyse as
      they only correspond to the evaluation of a reflex response; (ii) the tests
      dealing with more integrated responses are also more difficult to use and closely
      depend on the experimenter's subjectivity. If automation is widely used in a lot
      of research fields, this is not the case in behavioural pharmacology. Yet, it can
      contribute to optimize the tests. The use of signal processing devices allows the
      automated (and thus objective) measurement of behavioural reactions to
      nociceptive stimulation (amplitude of a reflex, vocal emission intensity).
      Mechanical devices based on a computer-driven dynamic force detector allows the
      recording of some pain behaviours. Video image analysis allows the quantification
      of more complex behaviours (nociception-induced specific motor behaviours) as
      well as meaningful information during the same experimentation (exploratory
      behaviour, total motor activity, feeding behaviour). Moreover, these methods make
      it possible to obtain a more objective measurement, to reduce animal-experimenter
      interactions, to ease system use, and to improve effectiveness. The prospects to
      work in this field are multiple: continuation of the attempts at an automation of
      the behaviours specifically induced by chronic pain; development of real animal
      pain monitoring based on analysis of specific and non-specific behavioural
      modifications induced by pain. In this context, the automation of the behavioural
      analysis is likely to make possible real ethical progress thanks to an increase
      in the test's effectiveness and a real taking into account of animal's pain.
      Nevertheless, there are some limits due to characteristics of the behavioural
      expression of nociception and technological problems.

PMID- 11243712
TI  - The role of endothelins and their receptors in heart failure.
AB  - Endothelin (ET) is a peptide composed of 21 amino acids, derived from a larger
      precursor, the big-endothelin, by action of the endothelin-converting enzyme
      (ECE) family; three isoforms of endothelin, named ET-1, ET-2 and ET-3, have been
      identified. Endothelin-1 is generated mainly by vascular endothelial cells and
      exerts various important biological actions, mediated by two receptor subtypes,
      ET-A and ET-B, belonging to the G protein-coupled family that have been
      identified in various human tissues such as the cardiac tissue. Endothelin-1 is a
      potent vasoconstrictive agent, has inotropic and mitogenic actions, modulates
      salt and water homeostasis and plays an important role in the maintenance of
      vascular tone and blood pressure in healthy subjects. Endothelin-1, as well as ET
      A and ECE-1, also has an important role in cardiovascular development, as
      observed by the variety of abnormalities related to neural crest-derived tissues
      in mouse embryos deficient of a member of the ET-1/ECE-1/ET-A pathway. Various
      evidence indicates that endogenous endothelin-1 may contribute to the
      pathophysiology of conditions associated with sustained vasoconstriction, such as
      heart failure. In heart failure, elevated circulating levels of both endothelin-1
      and big-endothelin-1 are observed; in failing hearts an activation of the
      endothelin system is found: tissue level of ET-1 is increased with respect to non
      failing hearts as well as receptor density, due mainly to an upregulation of the
      ET-A subtype, the prevalent receptor subclass in cardiac tissue. Finally, studies
      in both humans and animal models of cardiovascular disease show that inhibition
      of the endothelin function (anti-endothelin strategy) is associated with an
      improvement of haemodynamic conditions; these observations indicate that
      endothelin receptor antagonists or endothelin-converting enzyme inhibitors may
      constitute a novel and potentially important class of agents for the treatment of
      this disease.

PMID- 11243713
TI  - Lupeol, a triterpene, inhibits early responses of tumor promotion induced by
      benzoyl peroxide in murine skin.
AB  - The modulating effect of Lupeol [lup-20(29)-en-3 beta -ol], a triterpene found in
      many fruits and medicinal plants, on benzoyl peroxide-induced tumor promotion
      responses or tumor promotion in murine skin is described. Benzoyl peroxide is an
      effective cutaneous tumor promoter acting through the generation of oxidative
      stress, the induction of ornithine decarboxylase activity and the enhancement of
      DNA synthesis. Benzoyl peroxide treatment increases cutaneous microsomal lipid
      peroxidation and hydrogen peroxide generation. The activity of the cutaneous
      antioxidant enzymes, namely catalase, glutathione peroxidase, glutathione
      reductase and glutathione S-transferase, is decreased and levels of cutaneous
      glutathione are depleted. Benzoyl peroxide treatment also induces ornithine
      decarboxylase activity and enhances [3H]thymidine uptake in DNA synthesis.
      Prophylactic treatment of mice with lupeol (0.75 and 1.5 mg per animal) 1 hour
      before benzoyl peroxide treatment resulted in a diminution of benzoyl peroxide
      mediated damage. The susceptibility of cutaneous microsomal membrane to lipid
      peroxidation and hydrogen peroxide generation was significantly reduced (P< 0.01
      and P< 0.01, respectively). In addition, depleted levels of glutathione and
      inhibited activity of antioxidant enzymes were recovered to a significant level
      (P< 0.01, P< 0.05 and P< 0.01, respectively). Similarly, the elevated ornithine
      decarboxylase activity and enhanced thymidine uptake in DNA synthesis were
      inhibited significantly (P< 0.05) in a dose-dependent manner. The protective
      effect of lupeol was dose dependent in all parameters. The results suggest that
      lupeol is an effective skin chemopreventive agent that may suppress benzoyl
      peroxide-induced cutaneous toxicity.

PMID- 11243714
TI  - Tephrosia purpurea alleviates phorbol ester-induced tumor promotion response in
      murine skin.
AB  - In recent years, considerable emphasis has been placed on identifying new cancer
      chemopreventive agents, which could be useful for the human population. Tephrosia
      purpurea has been shown to possess significant activity against hepatotoxicity,
      pharmacological and physiological disorders. Earlier we showed that Tephrosia
      purpurea inhibits benzoyl peroxide-mediated cutaneous oxidative stress and
      toxicity. In the present study, we therefore assessed the effect of Tephrosia
      purpurea on 12-O-tetradecanoyl phorbal-13-acetate (TPA; a well-known phorbol
      ester) induced cutaneous oxidative stress and toxicity in murine skin. The pre
      treatment of Swiss albino mice with Tephrosia purpurea prior to application of
      croton oil (phorbol ester) resulted in a dose-dependent inhibition of cutaneous
      carcinogenesis. Skin tumor initiation was achieved by a single topical
      application of 7,12-dimethyl benz(a)anthracene (DMBA) (25 microg per animal per
      0.2 ml acetone) to mice. Ten days later tumor promotion was started by twice
      weekly topical application of croton oil (0.5% per animal per 0.2 ml acetone, v
      /v). Topical application of Tephrosia purpurea 1 h prior to each application of
      croton oil (phorbol ester) resulted in a significant protection against cutaneous
      carcinogenesis in a dose-dependent manner. The animals pre-treated with Tephrosia
      purpurea showed a decrease in both tumor incidence and tumor yield as compared to
      the croton oil (phorbol ester)-treated control group. In addition, a significant
      reduction in TPA-mediated induction in cutaneous ornithine decarboxylase (ODC)
      activity and [3H]thymidine incorporation was also observed in animals pre-treated
      with a topical application of Tephrosia purpurea. The effect of topical
      application of Tephrosia purpurea on TPA-mediated depletion in the level of
      enzymatic and non-enzymatic molecules in skin was also evaluated and it was
      observed that topical application of Tephrosia purpurea prior to TPA resulted in
      the significant recovery of TPA-mediated depletion in the level of these
      molecules, namely glutathione, glutathione S-transferase, glutathione reductase
      and catalase. From these data we suggest that Tephrosia purpurea can abrogate the
      tumor-promoting effect of croton oil (phorbol ester) in murine skin.

PMID- 11243715
TI  - Effects of the antioxidants curcumin or selenium on cisplatin-induced
      nephrotoxicity and lipid peroxidation in rats.
AB  - A large number of natural products and dietary components have been evaluated as
      potential chemoprotective agents. In the present investigation we report the
      effects of pre-treatment with two dietary antioxidants, curcumin (8 mg kg-1 body
      wt.) or selenium (1 mg kg-1 body wt.), on cisplatin-induced lipid peroxidation
      and nephrotoxicity in Wistar rats. Adult male rats were divided into six
      treatment and control groups of six rats each. The animals were pre-treated by
      gavage with two doses of each antioxidant, one dose 24 h and the second 10 min
      before cisplatin intraperitoneal injection (5 mg kg-1 body wt.). The rats were
      killed 3 days after cisplatin injection and serum, urine and kidney were isolated
      and analysed. Cisplatin administration resulted in significant reduction of body
      weight and higher urinary volumes were observed in all groups treated with this
      antitumor drug (P< 0.05). The animals treated with cisplatin showed a depletion
      of renal glutathione, increased lipid peroxidation, and an increase in serum
      creatinine levels (P< 0.05). The administration of curcumin or selenium alone did
      not increase lipid peroxidation compared to the control group (P> 0.05). Three
      days after curcumin or selenium plus cisplatin treatments, the renal damage
      induced by cisplatin did not recover at a significant statistically level. This
      study suggests that the natural antioxidants curcumin or selenium did not offer
      protection against cisplatin-induced nephrotoxicity and lipid peroxidation in
      adult Wistar rats.

PMID- 11243716
TI  - Effects of optical isomers of clenbuterol on the relaxant response in rat uterus.
AB  - Previous works have shown that the administration of the racemic beta 
      adrenoceptor agent clenbuterol produces a desensitization of the relaxant
      response in rat uterus. The aim of this work was to study the effects of the
      optical isomers of clenbuterol on the relaxant response in rat uterus. The
      administration of (L)-clenbuterol (0.25 mg per kg per day) over 1 or 10
      consecutive days, produced a reduction of the relaxant response to isoproterenol
      in uterine rings precontracted with 50 m m KCl from oestrogenic rats. The
      administration of (D)-clenbuterol (0.25 mg per kg per day) over 1 or 10 days did
      not affect the relaxant response of isoproterenol. (L)-clenbuterol also produced
      a concentration-dependent relaxant effect that was not observed with (D)
      clenbuterol. These results show that the beta-adrenergic relaxant response and
      the desensitization of the relaxant effect to isoproterenol is due to the (L)
      isomer and that the (D)-isomer is not involved in these effects.

PMID- 11243717
TI  - Pharmacokinetic study of methyldopa in aorta-coarctated rats using a
      microdialysis technique.
AB  - The pharmacokinetics of methyldopa (12.5, 25 and 50 mg kg(-1), i.p.) was studied
      in anesthetized sham-operated (SO) and abdominal aorta-coarctated (ACo) rats
      using a microdialysis technique. A non-linear relationship between the area under
      the curve (AUC) and dose was observed in SO rats. However, in ACo rats the AUC
      showed a proportional increase with dose. Abdominal aortic coarctation produced
      significant differences in the estimates of clearance (Cl) and the elimination
      rate constant from the dialysate (K(ed)) after the administration of 50 mg kg(
      1)of methyldopa (K(ed)SO, 0.31 +/- 0.09; ACo, 0.66 +/- 0.09(*)h(-1): Cl SO, 30.8
      +/- 10.1; ACo, 78.6 +/- 13.3(*)mlkg(-1)min(-1);n= 6,(*)P< 0.05 vs SO). In
      conclusion, this study, by using a microdialysis technique, suggests that
      abdominal aortic coarctation seems to produce changes in the pharmacokinetics of
      methyldopa in rats.

PMID- 11243718
TI  - Effect of iron and ascorbate on cyclosporine-induced oxidative damage of kidney
      mitochondria and microsomes.
AB  - The stimulatory effect of iron and ascorbate on the damaging action of
      cyclosporine in kidney mitochondria, microsomes and epithelial cells was
      examined. Cyclosporine induced malondialdehyde formation and hydrogen peroxide
      production in mitochondria and attenuated the activity of MnSOD and glutathione
      peroxidase. The damaging effect of cyclosporine (50 microM) plus Fe2+(20 microM)
      on mitochondrial and microsomal lipids and proteins as well as mitochondrial
      thiols was greater than the summation of the oxidizing action of cyclosporine
      alone and Fe2+ alone. As for tissue components, iron enhanced cyclosporine
      induced viability loss in kidney epithelial cells. Fe2+, EDTA and H2O2- induced 2
      alpha deoxyribose degradation was attenuated by 10 mM DMSO and 200 microM DTPA
      but not affected by 200 microM cyclosporine. The addition of Fe2+ caused a change
      in the absorbance spectrum of cyclosporine in the wavelength range 230-350 nm.
      The simultaneous addition of cyclosporine (50 microM) and ascorbate (100 microM)
      showed the enhanced peroxidative effect on mitochondrial and microsomal lipids,
      which was inhibited by DTPA and EDTA (1 mM). Similar to iron, ascorbate enhanced
      cyclosporine-induced cell viability loss. The results show that iron and
      ascorbate promote the damaging action of cyclosporine in kidney cortex
      mitochondria and microsomes and in kidney epithelial cells, which may contribute
      to the enhancement of cyclosporine-induced nephrotoxicity.

PMID- 11243719
TI  - Protective effects of flavonoids in the roots of Scutellaria baicalensis Georgi
      against hydrogen peroxide-induced oxidative stress in HS-SY5Y cells.
AB  - Oxidative stress plays an important role in the pathological process of
      neurodegenerative diseases. The effects of four major flavonoids present in
      Scutellaria baicalensis Georgi on hydrogen peroxide-induced neuronal cell damage
      are studied in this paper. When human neuroblastoma SH-SY5Y cells were incubated
      in Hanks' solution with the addition of 400 microM hydrogen peroxide for 2 h, the
      viability of cells was decreased remarkably, while the cell lipid peroxidation
      and the percentage of lactose dehydrogenase released into the culture medium was
      significantly increased. Addition of 10 microM of baicalein and baicalin
      significantly attenuated the cellular injury induced by hydrogen peroxide, while
      the effect of wogonin was marginal and wogonoside showed no effect at the tested
      concentration. In a separate experiment, 10 microM of baicalein and baicalin also
      antagonized the intracellular free-calcium concentration ([Ca2+]i) increase
      caused by 1 mM hydrogen peroxide. The effects of baicalein in both experiments
      were similar to those of quercetin, a well-studied antioxidant flavonoid. These
      results demonstrated the protective effects of flavonoids originating from
      Scutellaria baicalensis Georgi on the oxidative injury of neuronal cells.

PMID- 11243720
TI  - Ex vivo binding of flibanserin to serotonin 5-HT1A and 5-HT2A receptors.
AB  - Flibanserin has been reported to be an agonist at 5-HT1A-receptors and an
      antagonist at 5-HT2A receptors, with higher affinity for 5-HT1A receptors.
      Despite the fact that less receptor occupation is required by full agonists than
      by antagonists to exert their effects, flibanserin was shown to exert 5-HT2A
      antagonism at doses (4-5 mg kg-1) that are lower or equal to those required to
      stimulate 5-HT1A receptors. In order to understand this phenomenon, the
      interaction of flibanserin with 5-HT1A and 5-HT2A receptors was evaluated in ex
      vivo binding studies. This interaction was evaluated in the prefrontal cortex,
      hippocampus and midbrain by using [3H]8-OH-DPAT and [3H]ketanserin to label 5
      HT1A and 5-HT2A receptors, respectively. Flibanserin was given at 1, 10 and 30 mg
      kg-1 intraperitoneally. The dose of 1 mg kg-1 displaced both radioligands
      preferentially in the frontal cortex. The doses of 10 and 30 mg kg-1 reduced the
      binding of both radioligands in all the three brain regions non-selectively by
      about 50% and 70%, respectively. The displacement was maximal after 0.5 h and was
      reduced or not evident after 3 h. We conclude that 5-HT2 antagonism brought about
      by low doses of flibanserin may reflect functional mechanisms more than receptor
      mediated effects.

PMID- 11243721
TI  - Modulation of radiation-induced organs toxicity by cremophor-el in experimental
      animals.
AB  - Pharmacological and cytogenetic evaluations of the protective effects of
      polyethoxylated castor oil cremophor-EL (cremophor) against hepato, renal and
      bone marrow toxicity induced by gamma irradiation in normal rats were carried
      out. A single dose of irradiation (6 Gy) caused hepatic and renal damage
      manifested biochemically as an elevation in levels of serum alanine and aspartate
      aminotransferase as well as an increase in blood urea. Cremophor administration
      at a dose level of 50 microl kg-1 intravenously 1 day before exposure to
      irradiation (6 Gy) protected the liver and kidney as indicated by the recovery of
      levels of hepatic aminotransferase, urea and lipid profiles to normal values.
      Gamma irradiation of male rats caused a decrease in reduced glutathione and an
      increase in the oxidized form in rat-liver homogenate. A highly significant
      increase in the incidence of micronucleated normochromatic erythrocytes and
      micronucleated polychromatic erythrocytes was observed after irradiation
      exposure. The induced genotoxicity in the bone marrow cells was corrected by
      pretreatment with cremophor. The findings of this study suggest that cremophor
      pretreatment can potentially be used clinically to prevent irradiation-induced
      hepato, renal and bone marrow toxicity without interference with its cytotoxic
      activity.

PMID- 11243722
TI  - Effects of gemcitabine on cisplatin-induced nephrotoxicity in rats: schedule
      dependent study.
AB  - The effects of gemcitabine (dFdC) on the lipid peroxidation and kidney
      histopathology in the nephrotoxicity of an antitumour drug cisplatin (CDDP) were
      studied in rats. dFdC was administered intraperitoneally (i.p.) at single doses
      of 90 mgkg(-1) while CDDP was administered i.p. at single doses of 6 mgkg(-1).
      Both drugs were injected either alone or sequentially in combination. In one
      case, CDDP preceded dFdC by 4 h and 24 h and in the other case, dFdC preceded
      CDDP by 4 h and 24 h. Seven days after CDDP administration, the nephrotoxicity
      was manifested biochemically by elevation of serum creatinine, blood urea
      nitrogen and an increase in the kidney weight as a percentage of total body
      weight. In addition, marked decreases in serum albumin and calcium levels were
      observed. Lipid peroxidation in the kidney was monitored by measuring the
      malondialdehyde (MDA) production level and kidney glutathione (GSH) content,
      which were increased and depleted, respectively. Administration of dFdC 4 h and
      24 h after CDDP administration did not significantly change the indices of CDDP
      induced nephrotoxicity or the kidney platinum concentration levels in comparison
      with those animals treated with CDDP alone. On the contrary, administration of
      dFdC 4 h and 24 h prior to CDDP administration significantly aggravated CDDP
      induced nephrotoxicity which was manifested by severe increases in the serum
      creatinine and blood urea nitrogen levels as well as kidney weight as a
      percentage of total body weight. In addition, kidney tissue showed severe GSH
      depletion and increases in the MDA production and platinum concentration levels.
      Moreover, treatment of rats with dFdC 24 h prior to CDDP resulted in much more
      aggravation of CDDP-induced nephrotoxicity in comparison with those animals
      treated with dFdC 4 h prior to CDDP. Histopathological examination demonstrated
      tubular atrophy, tubular necrosis and drug-induced nuclear changes in the CDDP
      treated group. However, pretreatment of rats with dFdC 4 h and 24 h prior to CDDP
      revealed extensive interstitial nephritis, renal tubular atrophy and tubular
      necrosis with 'sloughing off' of the lining cells, especially with those rats
      treated with dFdC 24 h prior to CDDP. These results might suggest that
      administration of dFdC prior to CDDP enhanced the lipid peroxidation in kidney
      tissue and aggravated CDDP-induced nephrotoxicity.

PMID- 11243723
TI  - Nitric oxide inhibits norepinephrine stimulated contraction of human internal
      thoracic artery and rat aorta.
AB  - The effect of nitric oxide (NO) on norepinephrine-induced vascular contraction
      was evaluated using segments of rat aorta and human internal thoracic artery
      (ITA) and the NO donor, SNAP. NO levels were measured directly using an
      amperometric probe. Concentrations of NO greater than 2 nM were required to
      reduce vascular contraction induced by 100 nM norepinephrine (NE). Exposure of
      the aortic rings to SNAP prior to, or after NE addition, resulted in a similar
      attenuation of NE-induced contraction. In contrast, increased relaxation of ITA
      segments in response to SNAP was observed relative to that of rat aorta and
      significant development of contractile tone following NE addition was not
      observed. Evaluation of cytoskeletal actin demonstrated marked loss of F-actin
      content in smooth muscle cells following NO exposure, suggesting that NO may have
      direct and indirect effects on contractile tone. These data taken together
      suggest that vascular responsiveness to contractile agents may be significantly
      attenuated by prior or subsequent exposure to NO, and mechanisms in addition to
      vascular relaxation are likely to contribute to this effect.

PMID- 11243724
TI  - Impaired arachidonic (20:4n-6) and docosahexaenoic (22:6n-3) acid synthesis by
      phenylalanine metabolites as etiological factors in the neuropathology of
      phenylketonuria.
AB  - The recent literature on polyunsaturated fatty acid metabolism in phenylketonuria
      (PKU) is critically analyzed. The data suggest that developmental impairment of
      the accretion of brain arachidonic (20:4n-6) and docosahexaenoic (22:6n-3, DHA)
      acids is a major etiological factor in the microcephaly and mental retardation of
      uncontrolled PKU and maternal PKU. These fatty acids appear to be synthesized by
      the recently elucidated carnitine-dependent, channeled, mitochondrial fatty acid
      desaturases for which alpha-tocopherolquinone (alpha-TQ) is an essential enzyme
      cofactor. alpha-TQ can be synthesized either de novo or from alpha-tocopherol.
      The fetus and newborn would primarily rely on de novo alpha-TQ synthesis for
      these mitochondrial desaturases because of low maternal transfer of alpha
      tocopherol. Homogentisate, a pivotal intermediate in the de novo pathway of alpha
      TQ synthesis, is synthesized by 4-hydroxyphenylpyruvate dioxygenase. The major
      catabolic products of excess phenylalanine, viz. phenylpyruvate and
      phenyllactate, are proposed to inhibit alpha-TQ synthesis at the level of the
      dioxygenase reaction by competing with its 4-hydroxyphenylpyruvate substrate,
      thus leading to a developmental impairment of 20:4n-6 and 22:6n-3 synthesis in
      uncontrolled PKU and fetuses of PKU mothers. The data suggest that dietary
      supplementation with carnitine, 20:4n-6, and 22:6n-3 may have therapeutic value
      for PKU mothers and for PKU patients who have been shown to have a low plasma
      status of these essential metabolites.

PMID- 11243725
TI  - Enzyme replacement therapy in feline mucopolysaccharidosis I.
AB  - Enzyme replacement therapy (ERT) has long been considered an approach to treating
      lysosomal storage disorders caused by deficiency of lysosomal enzymes. ERT is
      currently used to treat Gaucher disease and is being developed for several
      lysosomal storage disorders now that recombinant sources of the enzymes have
      become available. We have continued development of ERT for mucopolysaccharidosis
      I (MPS I) using the feline model. Recombinant alpha-L-iduronidase was
      administered intravenously at low dose (approximately 0.1 mg/kg or 25,000
      units/kg) to four cats and high dose (0.5 mg/kg or 125,000 units/kg) to two cats
      on a weekly basis for 3- or 6-month terms. Clinical examinations showed distinct
      clearing of corneal clouding in one cat although clinical effects in the others
      were not evident. Biochemical studies of the cats showed that the enzyme was
      distributed to a variety of tissues although the liver and spleen contained the
      highest enzyme activities. Glycosaminoglycan storage was decreased in liver and
      spleen, and the histologic appearance improved in liver, spleen, and renal
      cortex. Enzyme was not consistently detected in cerebral cortex, brainstem, or
      cerebellum and the histologic appearance and ganglioside profiles did not
      improve. A variety of other tissues showed low variable uptake of enzyme and no
      distinct improvement. IgG antibodies to alpha-L-iduronidase were observed in five
      cats with higher titers noted when higher doses were administered. Mild
      complement activation occurred in three cats. Enzyme replacement therapy was
      effective in reversing storage in some tissues at the biochemical and histologic
      level in MPS I cats but an improved tissue distribution and prevention of a
      significant immune response could make the therapy more effective.

PMID- 11243726
TI  - A sequence variation in the mitochondrial glycerol-3-phosphate dehydrogenase gene
      is associated with increased plasma glycerol and free fatty acid concentrations
      among French Canadians.
AB  - FAD-dependent glycerol-3-phosphate dehydrogenase (mGPD) enzyme is located in the
      mitochondrial inner membrane where it catalyzes irreversible oxidation reactions.
      Type 2 diabetes mellitus (DM) is a multifactorial disorder associated with
      physiological abnormalities in the glycerol and free fatty acids (FFA) metabolic
      pathways. In the present study, we have evaluated the association among the mGPD
      H264R sequence variation and postabsorptive plasma FFA and glycerol
      concentrations in a sample of French Canadians with and without type 2 DM. A
      sample of 81 recently diagnosed type 2 DM and 318 nondiabetic, nonobese,
      normotriglyceridemic French Canadians were screened for the presence of the mGPD
      H264R genetic variant using a PCR-RFLP-based method. The 318 nondiabetic subjects
      were free of known type 2 DM covariates (fasting glucose <7.0 mmol/L, body mass
      index <29 kg/m(2), fasting glycerol <2.0 mmol/L and absence of the N288D sequence
      variation in the glycerol kinase gene, fasting triglyceride <2.5 mmol/L). The
      association of mGPD H264R sequence variation with plasma FFA and glycerol
      concentrations was assessed in different regression models. Among non-DM
      individuals, the R allele (HR and RR genotypes) was associated with increased
      plasma FFA and glycerol concentrations (P < 0.05). However, the mean plasma FFA
      and glycerol concentrations were not affected by the H264R genotype in the type 2
      DM sample. Overall, mean plasma FFA concentrations in non-DM RR homozygotes
      reached values that were similar to those achieved in patients with type 2
      diabetes (0.87 +/- 0.63 vs 0.90 +/- 0.48 mmol/L). After controlling for age,
      gender, body mass index, fasting glucose, and fasting triglyceride
      concentrations, the relative odds of having fasting plasma FFA levels above the
      90th percentile (0.9 mmol/L) in the absence of DM was increased by twofold in
      H264R heterozygotes (P = 0.04) and fourfold among R264 homozygotes (P = 0.009)
      compared to noncarriers. In the absence of DM, the mGPD R allele was also
      associated with higher plasma glycerol concentrations (P < 0.05). Results in non
      DM individuals suggest that the mGPD R allele is associated with DM intermediate
      phenotypes. The absence of a relation between mGPD genotype and DM is in
      accordance with the view that DM is a complex phenotype in which increased plasma
      FFA or glycerol concentrations result from metabolic alterations which might
      obscure the effect of the mGPD polymorphism.

PMID- 11243727
TI  - Prenatal diagnosis of succinic semialdehyde dehydrogenase deficiency: increased
      accuracy employing DNA, enzyme, and metabolite analyses.
AB  - Inherited succinic semialdehyde dehydrogenase (SSADH; EC1.2.1.24; McKusick
      271980) deficiency is a defect of GABA degradation which leads to accumulation of
      4-hydroxybutyric acid (gamma-hydroxybutyric acid; GHB) in physiologic fluids of
      patients. Prenatal diagnosis (PND) was performed in three at-risk pregnancies
      employing combinations of: (1) reverse-transcription-polymerase chain reaction
      (RT-PCR) and genomic DNA amplification followed by sequencing using isolated
      leukocytes or cultured human lymphoblasts; (2) GHB quantitation in amniotic
      fluid; or (3) SSADH enzyme assay in chorionic villus (CV) and/or amniocytes. In
      two pregnancies, all analyses were concordant for prediction of disease status in
      the fetus. In the third case, enzyme activity in CV (deficient) and metabolite
      analysis in amniotic fluid (normal) were discordant. For clarification, mutation
      analysis was undertaken in CV, confirming heterozygosity for the mutation
      previously identified in the proband. We hypothesize that delayed transit time
      for shipment of CV between Greece and the United States (8 days) led to enhanced
      degradation of heterozygous SSADH enzyme activity. Our data demonstrate the
      importance of combined metabolite, enzyme, and DNA analysis for increased
      accuracy in the PND of SSADH deficiency.

PMID- 11243728
TI  - Molecular diagnosis of Wilson disease.
AB  - Wilson disease (WD) is caused by mutations in the ATP7B gene. The diagnosis is
      based on clinical and biochemical criteria but these are increasingly recognized
      to have low sensitivity. Genetic diagnosis is considered impractical due to the
      large coding region of the ATP7B gene and extreme diversity of mutations. We
      assessed the feasibility and utility of genetic diagnosis in WD. The coding
      region of the ATP7B gene was scanned by single-stranded conformation polymorphism
      (SSCP) analysis in 6 cases in whom the diagnosis of WD was uncertain. In
      addition, we attempted molecular diagnosis in 26 WD patients of similar ethnicity
      but variable disease manifestations. In 6 individuals in whom the
      biochemical/clinical diagnosis was uncertain, DNA analyses were useful for
      assigning their status with respect to WD. Molecular diagnosis identified
      presymptomatic individuals in families affected by WD and assigned heterozygote
      carrier or wild-type status to individuals previously diagnosed as affected. In
      26 WD patients, 92% of disease alleles were identified. The most common mutations
      were H1069Q, L936X, and 2532delA representing 48, 10, and 8% of disease alleles,
      respectively. Three novel mutations were identified: Q898R, 3061(-1)g --> a, and
      3972insC. Genetic diagnosis is feasible for WD. Greater application of molecular
      diagnosis should enable an appreciation of the full spectrum of WD phenotype that
      is not possible with currently available diagnostic criteria.

PMID- 11243729
TI  - Subcutaneous abdominal adipocyte size, a predictor of type 2 diabetes, is linked
      to chromosome 1q21--q23 and is associated with a common polymorphism in LMNA in
      Pima Indians.
AB  - Large subcutaneous abdominal adipocyte size (s.c. abd. AS) is associated with
      insulin resistance and predicts type 2 diabetes in Pima Indians. Because type 2
      diabetes is familial, we aimed to determine whether mean s.c. abd. AS is also
      familial and if so, to identify chromosomal regions linked to this measure. Body
      composition (hydrodensitometry) and mean s.c. abd. AS (fat biopsy) were measured
      in 295 Pima Indians (179 with normal, 80 with impaired, and 36 with diabetic
      glucose tolerance) representing 164 nuclear families. Mean s.c. abd. AS, adjusted
      for age, sex, and percentage body fat was a familial trait (heritability h(2) =
      0.48, P < 0.0001). A genome-wide autosomal scan revealed suggestive evidence for
      linkage (LOD 1.73) of adjusted mean s.c. abd. AS to chromosome 1q21--q23, a
      region containing LMNA, the gene encoding for the nuclear envelope proteins lamin
      A/C. Rare mutations in LMNA were recently shown to underlie familial partial
      lipodystrophy (FPLD), a syndrome characterized by regional loss of adipose
      tissue, insulin resistance, and glucose intolerance. A common (allelic frequency
      0.43) single nucleotide polymorphism (silent 1908C --> T substitution) in exon 10
      of LMNA (GenBank X03444) was associated with reduced age-, sex- and percentage
      body fat-adjusted mean s.c. abd. AS [0.80 +/- 0.17 (CC), 0.76 +/- 0.15 (CT), 0.73
      +/- 0.16 (TT) microg lipid/cell, P < 0.05 for CC vs TT]. These findings indicate
      that approximately half of the variance in mean s.c. abd. AS can be attributed to
      familial factors and that genetic variation in LMNA might not only underlie rare
      cases of FPLD, but may also contribute to variation in adipocyte size in the
      general population.

PMID- 11243730
TI  - Metabolic studies of glycosphingolipid accumulation in mucopolysaccharidosis
      IIID.
AB  - Severe neurological deficits and mental retardation are frequently associated
      with disrupted ganglioside metabolism in a variety of gangliosidoses and
      lysosomal storage disorders. Accumulation of glycosphingolipids (GSLs) in the
      central nervous system (CNS) of humans and animals affected with several types of
      mucopolysaccharidoses (MPS) also correlates with the severity of neurological
      dysfunction. Mucopolysaccharidosis type IIID (MPS IIID) is characterized by
      deficiency in lysosomal N-acetylglucosamine 6-sulfatase activity and the
      accumulation and excretion of heparan sulfates and N-acetylglucosamine 6-sulfate.
      We investigated the metabolism of GSLs in the prenatal, neonatal, and adult MPS
      IIID caprine brains and an MPS experimental cell culture model. The amounts of
      total glycolipids in prenatal, neonatal, and adult MPS IIID caprine brains were
      about 2-fold higher than those in control samples. GM3, GD3, and lactosyl
      ceramide were the principal GSLs which abnormally accumulated in caprine MPS IIID
      brains. These changes may be, in part, due to the reduction of sialidase and UDP
      N-acetylgalactosamine:GM3 N-acetylgalactosaminyltransferase (GalNAc-T) activities
      in MPS IIID caprine brain. To further examine the possible mechanism of GSL
      accumulation in MPS IIID brains, we employed a cell culture model using suramin
      treated neuronal cultures of differentiated P19 cells. HPTLC analysis showed
      elevated GSLs in suramin-treated cells. Metabolic pulse-chase labeling study
      revealed that the GSL accumulation in suramin-treated cells may be attributed to
      both disturbed biosynthesis and significantly slower degradation of GSLs. In
      addition, the consistency of observations in the cell culture and caprine models
      supports the cell culture system as a means of evaluating GSL metabolic
      perturbations.

PMID- 11243731
TI  - Identification of a 55-bp deletion in the glucocerebrosidase gene in Gaucher
      disease: phenotypic presentation and implications for mutation detection assays.
AB  - A 55-bp deletion in exon 9 of the glucocerebrosidase gene was identified in a 28
      year-old male affected with Gaucher disease. The diagnosis was established during
      an evaluation for mild pancytopenia and was confirmed by bone marrow histology
      and biochemical studies. The patient is of German ancestry. Initial DNA testing
      indicated homozygosity for the N370S mutation. However, subsequent testing of the
      patient's parents suggested that the patient and his mother carried a null allele
      by our assay for N370S. Further molecular studies identified a 55-bp deletion in
      exon 9 of the glucocerebrosidase gene (g.6767_6822del55). This deletion has been
      previously reported in a patient with severe Gaucher disease (1), and is present
      in the glucocerebrosidase pseudogene. In the previously reported case, initial
      DNA testing also suggested the genotype N370S/N370S, but further mutation studies
      were undertaken because clinical severity was greater than expected for that
      genotype. In contrast, our patient has an unusually mild clinical course. Thus,
      clinical severity cannot be reliably used to determine when to test for the
      presence of the 55-bp deletion. While the 55-bp deletion is not reported to be
      common, its actual frequency may be underestimated since it eludes detection by
      many standard clinical assays for Gaucher disease. This report points out the
      need to consider this deletion mutation which may cause erroneous interpretation
      of results in existing assays for the common mutations N370S and L444P.
      Furthermore, the importance of recommending parental analysis for individuals who
      test homozygous for autosomal mutations is highlighted.

PMID- 11243732
TI  - Mutation of proline 409 to arginine in the meander region of cytochrome p450c17
      causes severe 17 alpha-hydroxylase deficiency.
AB  - We elucidated the molecular basis of 17 alpha-hydroxylase deficiency in a Chinese
      patient with male pseudohermaphroditism. The patient is a compound heterozygote,
      carrying two different mutant alleles in the CYP17 gene. The first mutation,
      g.6333--6341delGACTCTTTCA, located in exon 8, was reported in a Thai patient
      living in a rural village in Thailand. We suggest that g.6333--6341delGACTCTTTCA
      may be a prevalent mutation causing P450c17 deficiency in Southeast Asia. The
      second mutation is a missense mutation, g.5582C>G, located in exon 7, changing
      the codon 409 from CCG to CGG, and changing the coded amino acid from proline to
      arginine, i.e., P409R. This proline residue is conserved in P450c17 of other
      species and other human P450 proteins. Site-directed mutagenesis, in vitro
      expression, and functional analysis of the P409R mutant in COS-1 cells show that
      it has a complete lack of 17 alpha-hydroxylase activity. The proline residue
      probably causes a turn in the meander region of P450c17, and we hypothesize, by
      comparison to homologous proteins, that the change in the protein conformation
      may abolish heme incorporation or may prevent P450c17 from interacting with
      electron donors.

PMID- 11243734
TI  - Placental floor infarction complicating the pregnancy of a fetus with long-chain
      3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency.
AB  - By postmortem biochemical and molecular genetic analyses, an 8-month-old infant
      was diagnosed with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency,
      an inborn error of mitochondrial fatty acid beta-oxidation. He was born following
      a pregnancy complicated by a maternal floor infarction of the placenta, a
      disorder of unknown etiology. We speculate that the child's autosomal recessive
      fatty acid beta-oxidation disorder and the pregnancy complication are causally
      related.

PMID- 11243733
TI  - 2,8-Dihydroxyadenine urolithiasis in a patient with considerable residual adenine
      phosphoribosyltransferase activity in cell extracts but with mutations in both
      copies of APRT.
AB  - We have examined the mutational basis of adenine phosphoribosyltransferase (APRT,
      EC 2.4.2.7) deficiency (MIM 102600) in a patient of Polish origin who has been
      passing 2,8-dihydroxyadenine (DHA) stones since birth, but has considerable
      residual enzyme activity in lymphocyte extracts. The five exons and flanking
      regions of APRT were amplified by PCR and then sequenced. A single T insertion
      was identified at the intron 4 splice donor site (TGgtaa to TGgttaa:IVS4+2insT)
      in one allele from the proband, his mother, and brother. A G-to-T transversion in
      exon 5 (GTC-to-TTC:c.448G>T, V150F) was identified in the other allele, and this
      mutation was also present in one allele from the father and the paternal
      grandmother. Tru91 and AvaII digestions of PCR products spanning exons 4 and 5,
      respectively, confirmed the mutations. The mother was heterozygous for an
      intragenic TaqI site, but all other family members were homozygous for the
      presence of this site. IVS4+2insT, located on the allele containing the TaqI
      site, has been identified previously in several families from Europe, suggesting
      a founder effect, but the substitution in exon 5 is a novel mutation. IVS4+2insT
      is known to result in complete loss of enzyme activity, and our results suggest
      that V150F produces an enzyme that is nonfunctional in vivo but has considerable
      residual activity in vitro.

PMID- 11243735
TI  - Congenital lactic acidosis: evaluation of the properties of the a199t natural
      variant of human pyruvate dehydrogenase e1alpha by in vitro mutation.
AB  - One cause of congenital lactic acidosis is a mutation in the E1 alpha-subunit of
      the pyruvate dehydrogenase multienzyme complex. Little is known about the
      consequences of these mutations at the enzymatic level. Here we study the A199T
      mutation by expressing the protein in Escherichia coli. The specific activity is
      25% of normal and the K(m) for pyruvate is elevated by 10-fold. Inhibitors of
      lactate dehydrogenase might be a useful therapy for patients with such mutations.

PMID- 11243736
TI  - Nonorthologous gene displacement of phosphomevalonate kinase.
AB  - Phosphomevalonate kinase (PMK; EC 2.7.4.2) catalyzes the phosphorylation of 5
      phosphomevalonate into 5-diphosphomevalonate, an essential step in isoprenoid
      biosynthesis via the mevalonate pathway. So far, two nonorthologous genes
      encoding PMK have been described, the Saccharomyces cerevisiae ERG8 gene and the
      human PMK gene. Here, we report that orthologues of ERG8 are present in
      eubacteria, fungi, and plants, while orthologues of human PMK are found only in
      animals, indicative of a nonorthologous gene displacement early in animal
      evolution. This also is reflected by different consensus ATP-binding motifs: a
      protein kinase motif in the ERG8 orthologues versus a P-loop or Walker A motif in
      the animal orthologues. The fact that ERG8 orthologues are found in pathogenic
      eubacteria and fungi but not in man makes them attractive targets for the
      development of antibacterial and/or antifungal drugs.

PMID- 11243737
TI  - Effects of testosterone and photoperiodic condition on song production and vocal
      control region volumes in adult male dark-eyed juncos (Junco hyemalis).
AB  - In seasonally breeding male oscines, song learning and expression are controlled
      by brain regions (vocal control regions, VCRs) that exhibit seasonal neural
      plasticity in adulthood. Several VCRs contain androgen receptors, and gonadal
      androgens play important roles in the control of seasonal structural and
      functional changes of VCRs. Recent studies also found that adult VCRs are
      influenced by factors other than gonadal hormones, including photoperiod, but the
      relative importance of these factors and their mechanisms of action are poorly
      understood. To address this issue, we investigated the contributions of
      photoperiod and testicular androgens to the regulation of VCR volumes and to the
      control of song expression in adult dark-eyed juncos, Junco hyemalis. Exposing
      castrated (CX) photosensitive males to long days (LD) enhanced their high vocal
      center (HVc) volumes compared to those of males held on short days (SD). These
      volumes were not further increased by concurrent testosterone (T) treatment,
      revealing a marked and gonadal androgen-independent stimulatory influence of
      photoperiod on the size of this brain region. HVc sizes were smaller in LD
      exposed photorefractory than photosensitive males irrespective of whether birds
      were intact or had been castrated before photoperiodic manipulations, but HVc
      sizes increased in response to T treatment in intact photorefractory males. Thus,
      LD exposure can increase HVc volumes in the absence of gonadal T, but large
      volume induction in photorefractory males requires elevated plasma T levels.
      Testosterone treatment of SD-exposed photosensitive males increased HVc, but not
      Area X, MAN, or RA volumes. Only T-treated males sang and this treatment given to
      castrates was equally effective behaviorally when administered to photosensitive,
      photostimulated, or photorefractory juncos. This result indicates that the
      stimulating influence of LD exposure on HVc volumes is insufficient to induce
      song in the absence of elevated plasma T levels.

PMID- 11243738
TI  - Bromocriptine administration lowers serum prolactin and disrupts parental
      responsiveness in common marmosets (Callithrix j. jacchus).
AB  - The influence of prolactin on parental responsiveness was investigated in eight
      unpaired, parentally inexperienced common marmosets (Callithrix jacchus; 6
      female, 2 male). The marmosets were prescreened with infants (1-10 days of age)
      and required to exhibit short latency retrieval and infant carrying in at least
      three consecutive pretests as criterion for inclusion in this study. The
      marmosets were then administered the dopamine agonist bromocriptine (0.5 mg/0.5ml
      vehicle subcutaneously) and the vehicle alone (0.5 ml 10% ethanol solution) twice
      daily for 3 consecutive days in random order. Bromocriptine treatment reduced
      circulating prolactin to nondetectable levels. Bromocriptine treatment eliminated
      infant retrieval in four of the eight marmosets and was associated with
      significantly increased retrieval latencies and significantly reduced carrying
      durations in the four monkeys that continued to retrieve following bromocriptine
      treatment. When given the vehicle alone, the marmosets retrieved infants
      significantly faster than during pretests, suggesting a handling effect of the
      injection series. Bromocriptine treatments were associated with significantly
      increased movement during the tests. The results of this study indicate that
      prolactin and/or its regulatory neurotransmitters are involved in the control of
      the spontaneous display of parental responsiveness in common marmosets.

PMID- 11243739
TI  - Evidence for extended action of gonadal hormones on the organization of sexually
      dimorphic behavior and morphology in gray short-tailed opossums (Monodelphis
      domestica).
AB  - Male and female gray short-tailed opossums were gonadectomized (GDX), or treated
      with the estrogen receptor antagonist tamoxifen citrate (TX), or corn oil (OIL)
      (control) during the 5th postnatal week, a time period equivalent to the 3rd
      postnatal week in rats and associated with high levels of circulating gonadal
      hormones and neural aromatase activity in this marsupial species. In adulthood
      following gonadectomy (for animals not previously gonadectomized) and replacement
      therapy with estradiol or testosterone, GDX males showed less male-typical scent
      marking and had shorter phalluses than OIL and TX males. Following replacement
      therapy with estradiol, GDX females were more likely to fight with and less
      likely to mate with stimulus males than TX females; OIL females were intermediate
      in these measures. Along with previous findings, these results suggest that
      gonadal hormones act over an extended postnatal period to organize sexually
      dimorphic behavior and morphology in male gray opossums and may have some effect
      on the organization of aggressive behavior in females of this species.

PMID- 11243740
TI  - Systemic ICI 182,780 alters the display of sexual behaviors in the female rat.
AB  - The present study investigates the effects of the antiestrogen ICI 182,780 (ICI)
      on the display of sexual behaviors in female rats. ICI 182,780 is a pure anti
      estrogen and when given systemically, ICI is thought to act only in the
      periphery, and is not believed to cross the blood brain barrier. The present
      study examines the effects of ICI on sexual receptivity and on paced mating
      behavior following treatment with estradiol benzoate (EB) and progesterone (P)
      (Experiment 1) or with EB alone (Experiment 2). In Experiment 1, ICI (250.0
      microg) did not affect the display of receptivity or paced mating behavior
      induced by EB and P. In contrast, in Experiment 2 female rats receiving EB alone
      displayed a decrease in the level of sexual receptivity following treatment with
      500.0 and 750.0 microg ICI (but not 250.0 microg ICI). In addition, in Experiment
      2 EB-treated female rats receiving 250.0 microg ICI spent more time away from the
      male rat following an intromission and were more likely to exit from the male
      compartment following a mount. Last, ICI had potent antiestrogenic effects on
      vaginal cytology (Experiment 2) and on the uterus (Experiments 1 and 2). The
      present study supports a role for peripheral estrogen receptors in sexual
      receptivity and paced mating behavior and suggests that estrogen receptor
      activation may decrease the aversive sensation associated with sexual
      stimulation.

PMID- 11243742
TI  - 20-hydroxyecdysone causes increased aggressiveness in female American lobsters,
      Homarus americanus.
AB  - Lobsters become transiently more aggressive before ecdysis. This aggressiveness
      accompanies an increase in hemolymph titers of 20-hydroxyecdysone (20-HE).
      Combats between intermolt female lobsters, injected with premolt levels of 20-HE,
      and larger, saline-injected opponents were videotaped. Aggressive, defensive, and
      avoidance behaviors were ranked according to aggressiveness in a Rank of
      Aggression hierarchy, which included opponent-directed and (nonopponent)
      redirected behaviors. Treated animals performed more and more highly aggressive
      behaviors than saline-injected controls. Opponents of treated animals performed
      fewer aggressive behaviors than saline-injected control opponents. Controls
      performed more defensive behaviors than treated animals, when redirected
      behaviors were considered. Differences in avoidance behaviors among the four
      types of combatants were not significant. The total aggressive content was the
      same in treated and control fights, but the interactions between combatants in
      the two fights were significantly different. Treated animals were equally as
      aggressive and defensive as their opponents; controls were relatively less
      aggressive and more defensive than their opponents. These results correlate with
      molt-cycle variations in behavior, 20-HE titers, and the effects of 20-HE and
      molt-differentiated hemolymph on the claw opener muscle. They suggest that 20-HE
      orchestrates intrinsic, cellular, and nuclear events that produce the molt-cycle
      transformations in agonistic behavior and aggressive state of lobsters.

PMID- 11243741
TI  - Developmental effects of testosterone on behavior in male and female green anoles
      (Anolis carolinensis).
AB  - This study addressed the role of testosterone (T) in the development of sexually
      dimorphic behavior in the green anole lizard, Anolis carolinensis. We documented
      the pattern of endogenous T concentrations during ontogeny and we determined the
      behavioral effects of experimentally elevated T in juvenile males and females. T
      concentrations were measured in the plasma of hatchlings from eggs incubated in
      the laboratory, in juveniles of all sizes sampled in the field, and in the yolks
      of freshly laid eggs in the laboratory and were compared to plasma T in adult
      females (measured in this study) and adult males. There were no sex differences
      in plasma T in hatchling and small juvenile (<26-mm snout-vent length, SVL; <14
      days old) males and females, concentrations of which in both sexes tended to
      decline over the 14-day posthatching period. Plasma T sharply increased in
      juvenile males, but not females, after approximately 14 days posthatching (>25-mm
      SVL), and it became significantly higher after approximately 38 days posthatching
      (>30-mm SVL). Plasma T for juvenile males was within the range detected in
      breeding adult females, but it was 20- to 45-fold lower than that of adult males,
      breeding or postbreeding. All eggs contained detectable yolk T, but eggs that
      gave rise to males contained nearly twice as much yolk T as those that gave rise
      to females. We do not know whether this yolk T comes from the mother, embryo, or
      both. In behavior trials conducted in the laboratory, juveniles (36- to 42-mm
      SVL) with T implants, regardless of whether they were male or female, had
      increased activity levels compared to juveniles with blank implants, due to
      increased rates of nearly every behavior monitored. These results are discussed
      in the context of the organization-activation theory of sexual differentiation
      and the particular life history of A. carolinensis.

PMID- 11243743
TI  - Effects of androgens on social behavior and morphology of alternative
      reproductive males of the Azorean rock-pool blenny.
AB  - In the Azorean rock-pool blenny Parablennius sanguinolentus parvicornis two
      sequential reproductive tactics occur. Larger and older males establish breeding
      territories, while some of the smaller males become attached to nest-holder
      territories, acting as satellites on these territories, which they help to defend
      while trying parasitic fertilizations when females go in the nests to spawn. In
      the present paper we tested the effects of the androgens 17alpha
      methyltestosterone (MT) and 11-ketotestosterone (KT) in the expression of male
      secondary sex characters and bourgeois behavior in satellite males. One week
      after satellites were implanted with Silastic tubes containing MT, KT, or castor
      oil (control), androgen-treated satellites had developed male secondary sex
      traits such as longer and wider male-type genital papilla and anal glands that
      secrete a sex pheromone, both traits being less expressed or absent,
      respectively, in satellite males. Androgen treatment had no effect on the
      gonadosomatic index or on the development of the testicular gland. KT treatment
      had a positive effect on relative liver weight. In terms of behavior, androgen
      implanted individuals were less aggressive both in a mirror test and toward
      females when these were introduced into their tanks. MT-treated individuals spend
      more time inside the provided nests. Only androgen-implanted satellites managed
      to have the females entering their nests. When given a chance in a group tank
      either to try to attract females to their own nest or to act as satellites of an
      already established nest-holder's nest, MT-implanted males spent significantly
      more time in their own nest than near the nest-holder nest. These data suggest
      that androgens, particularly testosterone, may be involved in mating tactic
      switching in this species.

PMID- 11243744
TI  - Gonadectomy impairs T-maze acquisition in adult male rats.
AB  - Recent studies have shown that chronic gonadectomy increases the density of
      dopaminergic axons in prefrontal but not sensorimotor cortices in adult male
      rats. Since supranormal prefrontal cortical dopamine stimulation is known to
      impair rats' performance in T-maze delayed alternation paradigms, we tested
      whether long-term gonadectomy might also impair T-maze performance. For
      comparison, sensorimotor functions were also assessed. Adult male rats were
      gonadectomized and placebo-, estradiol-, or testosterone propionate-treated or
      were sham operated and placebo-treated. Four weeks after surgery, the subjects
      were tested using a rotorod apparatus and in the acquisition of a T-maze delayed
      alternation paradigm. Gonadectomized placebo-treated and estradiol-treated rats
      took significantly longer to acquire the T-maze rule than controls, and
      gonadectomized, testosterone-treated rats acquired the task within the same time
      frame as controls. No group differences were detected in rotorod performance.
      Thus, chronic gonadectomy induced testosterone-sensitive, estradiol-insensitive
      acquisition deficits in a spatial learning task but had no demonstrable effects
      on the sensorimotor functions tested.

PMID- 11243745
TI  - Can a nine-month regimen be used to treat isoniazid resistant tuberculosis
      diagnosed after standard treatment is started?
AB  - OBJECTIVES: National tuberculosis treatment guidelines suggest a regimen of
      2RZE/10RE for the treatment of isoniazid resistant organisms. A retrospective
      clinical study of all patients treated for non-MDR-TB isoniazid-resistant
      organisms was undertaken. METHODS: A continuous database of the patients treated
      between 1978-1999 inclusive was examined to determine the regimens used and the
      outcome of treatment for such patients. RESULTS: Thirty-seven patients were
      identified. Eighteen had regimens of greater than 9 months, 19 had regimens of 9
      months or less. No relapses occurred in those cases treated with a regimen of
      2RZE/7RE during 12 months' minimum follow-up. CONCLUSIONS: A regimen of 2RZE/7RE
      may be possible for the treatment of isoniazid-resistant organisms if given
      either under close supervision or as a formally supervised regimen. Larger
      clinical studies or a controlled clinical trial are needed to confirm these
      initial findings.

PMID- 11243746
TI  - Low levels of HIV-1 plasma viral load in patients infected with HIV-1 subtype b
      and advanced immunosuppression.
AB  - OBJECTIVES: Some HIV-1 infected patients show low levels of viraemia despite
      having advanced immunosuppression. Cases with falsely undetectable viraemia by
      conventional PCR have been reported when patients were infected with non-B
      subtypes. The aim of this study was to investigate whether this immunovirological
      discordance can be due to the presence of HIV-1 non-B subtypes, and whether a
      modified PCR procedure can yield different HIV viraemia values in these cases.
      METHODS: Fifteen HIV-infected patients either naive for antiretroviral drugs or
      under treatment, with HIV plasma viraemia below 1000 copies/mm(3)and CD4+ cell
      counts lesser than 500 or 300 cells/mm(3), respectively, were included.
      Serotyping, genotyping and HIV plasmatic viraemia determinations were performed
      in all individuals. RESULTS: In five out of six treatment-naive patients the
      virus was categorized as non-B subtype by serotyping, although only one case was
      confirmed by genotyping as HIV-2. Eight out of nine patients under antiretroviral
      therapy were subtype B carriers by serotyping and confirmed by genotyping. The
      remaining patient was determined as a subtype A carrier by both procedures. A
      modified PCR procedure (Amplicor HIV Monitor Test version 1.5) did not yield
      higher viral load levels than the former version. CONCLUSIONS: The presence of
      HIV-1 subtypes non-B can explain a minority of cases of this immunovirological
      discordance, but in most of them the reason is still unknown. Likewise, a PCR
      procedure adapted for detecting HIV-1 non-B subtypes fails to find higher plasma
      viraemia in patients with such a discordance.

PMID- 11243747
TI  - Twice-weekly pyrimethamine-sulfadoxine effectively prevents Pneumocystis carinii
      pneumonia relapse and toxoplasmic encephalitis in patients with AIDS.
AB  - OBJECTIVE: To evaluate the safety and efficacy of a fixed 25mg pyrimethamine-
      500mg sulfadoxine combination plus 15mg folinic acid given twice weekly for the
      prevention of relapses of Pneumocystis carinii pneumonia (PCP) and primary
      episodes of toxoplasmic encephalitis. METHODS: Ninety-five HIV-infected patients
      with successfully treated PCP and without history of toxoplasmic encephalitis
      were enrolled between January 1990 and October 1995 in a single-arm open-label
      prospective study. No patient was receiving highly active antiretroviral
      treatment, including protease inhibitors or non-nucleoside reverse transcriptase
      inhibitors, while on study medication. Efficacy was analysed on an "as-treated"
      basis. RESULTS: Five patients (5.3%) suffered a PCP relapse while on study
      medication, three of whom had been non-compliant. No relapse occurred in the
      first year. Probabilities of freedom from relapse were 0.96 after 24 months and
      0.90 after 36 months. Of 69 patients positive for anti-toxoplasma IgG antibodies,
      one (1.5%) developed cerebral lesions compatible with toxoplasmic encephalitis
      after 50 months. Cutaneous allergic reactions were observed in 16 patients
      (16.8%) resulting in permanent discontinuation in six patients (6.3%). Two
      patients (2.1%) developed serious adverse reactions (Stevens-Johnson syndrome),
      both of whom had continued prophylaxis despite progressive hypersensitivity
      reactions. CONCLUSIONS: The prophylactic regimen used is effective in preventing
      PCP relapses and toxoplasmic encephalitis. The regimen appears to be safe. Severe
      adverse events can likely be prevented by discontinuation of prophylaxis at the
      time allergic reactions are noted. Rechallenge frequently results in tolerance of
      the regimen. Efficacy and safety compare favourably with previously studied
      regimens. This simple prophylactic regimen may provide a convenient alternative
      for patients unable to tolerate approved regimens.

PMID- 11243749
TI  - Change in plasma viral load, and viral DNA and mRNA burdens, in peripheral blood
      mononuclear cells from patients infected with HIV-1.
AB  - OBJECTIVES: To clarify the virological state of human immunodeficiency virus
      (HIV)-1-infected patients, we compared the plasma HIV-1 RNA copy number (plasma
      viral load (VL)), viral DNA and mRNA burdens in peripheral blood mononuclear
      cells (PBMCs), and the other clinical predictors. METHODS: One hundred and thirty
      one samples of PBMCs and plasma from 26 patients infected with HIV-1 were
      obtained during 20 consecutive months for the measurement of VL, viral DNA and
      mRNA burdens, and CD4 positive (CD4+) cells count. The quantitative polymerase
      chain reaction (PCR) method with detection by solid phase DNA was utilized for
      the assay of VL, viral DNA and mRNA burdens. RESULTS: Eighty-six VL, 101 viral
      mRNA and 129 viral DNA out of 131 samples were detected. There was a significant
      positive correlation between VL and the viral mRNA burden (r = 0.600, P < or =
      0.001), and between VL and the viral DNA burden (r = 0.368, P < or = 0.001).
      Focused on individuals, the viral mRNA burdens varied in a manner relatively
      dependent on VL when both values were detectable. However, viral DNA burdens
      varied relatively independently of VL and the viral mRNA burdens. In six patients
      the viral mRNA burden was detectable and changed even if the VL was undetectable
      throughout the observation period. CONCLUSIONS: Both viral DNA and viral mRNA
      burdens still showed detectable changes even when the VLs became undetectable in
      most patients. The measurement of viral mRNA or DNA burdens may be clinically
      available to identify viral replication when VL is undetectable.

PMID- 11243748
TI  - Success in the toxoplasma dye test.
AB  - OBJECTIVES: To compare the success rate of the toxoplasma dye test using
      different accessory factors (human serum as a source of complement) and different
      batches of tachyzoites produced in vivo and in vitro. METHODS: Twenty-five
      accessory factors were used in the dye test to assess both types of tachyzoite.
      Batches of tachyzoites were produced in vivo (n = 49) and in vitro (n = 23) and
      their performance assessed against panels of accessory factors. Performance was
      recorded as success or failure (incorrect results, total killing or no killing).
      RESULTS: With in vivo tachyzoites 21/25 accessory factors were successful in P >
      or = 1 dye test runs, whereas with in vitro tachyzoites all 25 were successful.
      One or more failure was recorded for 19/25 and 12/25 accessory factors using in
      vivo and in vitro tachyzoites, respectively (P < 0.05). The number of successful
      dye test runs was less for in vivo (92/141, 65%) than in vitro (140/163, 86%)
      tachyzoites (P < 0.001). This was due to a higher success rate in citrated
      accessory factors used for in vitro tachyzoites compared to the corresponding
      uncitrated accessory factors used for in vivo tachyzoites (P < 0.001). Success in
      the dye test was recorded for 48/49 and 23/23 batches of in vivo and in vitro
      tachyzoites, respectively. The number of successful dye test runs was lower with
      in vivo (156/234, 67%) than in vitro (116/142, 82%) tachyzoites (P < 0.01).
      CONCLUSIONS: Success in the dye test may be due to the accessory factor,
      tachyzoites, or a combination of both. Problems due to the accessory factor can
      be minimized by careful quality control or use of modification procedures.
      Tachyzoites produced in vitro may also increase success in the dye test. Careful
      selection of accessory factor/tachyzoite combination makes it possible to use the
      dye test in a district general hospital.

PMID- 11243750
TI  - Pan-Thames survey of occupational exposure to HIV and the use of post-exposure
      prophylaxis in 71 NHS trusts.
AB  - OBJECTIVES: To review the management of occupational exposure to definite or
      suspected HIV-infected blood, following the introduction of the 1997 UK
      Department of Health guidelines on the use of post-exposure prophylaxis. METHODS:
      Cross-sectional telephone survey of protocols in 71 NHS Trusts in the Pan-Thames
      region. Retrospective postal survey of the management of each definite or
      suspected HIV blood exposure between 1 July 1997 and 30 June 1999. RESULTS: Sixty
      two (93%) Trusts had a written protocol, with many specialties involved in
      exposure management. Twenty-four Trusts reported 171 occupational exposures to
      definite or suspected HIV-infected blood. Of 97 definite HIV exposures, eight
      (8%) were discovered on post-incident HIV testing of the source patient; to which
      most source patients agreed when approached. Seventy-two (74%) exposed health
      care workers started prophylaxis and 49 (68%) completed the recommended 4-week
      course. Only half of those whose exposures occurred more than 6 months ago were
      known to have had a follow-up HIV test. CONCLUSIONS: Although most Trusts have
      implemented the Department of Health's guidance, collecting data on individual
      exposures proved difficult. We suggest that a designated department in each Trust
      co-ordinates and records HIV exposure management. Routine HIV testing is
      acceptable to most source patients and is appropriate in areas with a high
      prevalence of HIV seropositivity.

PMID- 11243751
TI  - The acute phase response in Sicilian patients with boutonneuse fever admitted to
      hospitals in Palermo, 1992-1997.
AB  - OBJECTIVES: To study the modifications of some components of the acute phase
      response (APR) in Sicilian patients with boutonneuse fever (BF) caused by
      Rickettsia conorii. METHODS: Sera from 500 Sicilian patients with confirmed BF
      were studied at the time of diagnosis and every week after treatment, and after
      recovery for the presence of various inflammatory mediators. Tumour necrosis
      factor alpha (TNFalpha), interleukin(IL)-6, IL-1alpha, IL-8, soluble TNF
      receptors (sTNF-R) and sIL-6R were assayed by commercially ELISA kits. C3, C4,
      factor B, C-reactive protein (CRP), fibrinogen, ceruloplasmin (Cp) and alpha(1)
      antitrypsin (AAT) were assayed by a rate nephelometry. RESULTS: Interferon gamma
      (IFNgamma), IL-6, TNFalpha, and IL-10 cytokines were significantly modified,
      whereas IL-1 and IL-8 were not detectable in the blood in any phase of infection.
      sTNF-RI, sTNF-RII and sIL-6 were significantly increased in the first 2 weeks of
      infection, but sTNF-R levels were not related to the plasma levels of TNFalpha,
      whereas sIL-6 was directly related to serum IL-6 concentrations. C3, C4, factor B
      and CRP were significantly increased in the first 2 weeks of infection, but
      afterwards returned to the normal range, even though CRP was still high in the
      third week and C3 persisted high after the fourth week. Fibrinogen was high only
      in the first week in relation to the injury to the endothelial cells (ECs). The
      anti-inflammatory proteins, Cp and AAT, were extremely high in the first 2 weeks
      of infection acting as a buffer of APR activation. CONCLUSIONS: These results
      suggest that R. conorii is able to elicit, after invasion and proliferation in
      the ECs, the activation of APR. Further work is required to establish if active
      inhibitory mechanisms are operating during APR, or if there is a spontaneous
      decay in the initiation events.

PMID- 11243753
TI  - Bacteraemia and mortality among adult medical admissions in Malawi--predominance
      of non-typhi salmonellae and Streptococcus pneumoniae.
AB  - OBJECTIVES: The high seroprevalence of HIV in Malawi might be expected to alter
      the pattern of pathogens isolated from bacteraemic patients. We aimed to describe
      the frequency and seasonal pattern of bacterial isolates from blood, their
      antibiotic susceptibility, and patient outcome, in order to provide data on which
      to base empirical antibiotic therapy and further studies of pathogenesis.
      METHODS: Over a 12-month period, blood cultures were taken from all febrile adult
      medical admissions to Queen Elizabeth Central Hospital, Blantyre. RESULTS: A
      total of 2789 out of 9298 adult general medical admissions had blood culture
      performed, of whom 449 (16.1%) grew significant pathogens. Non-typhi salmonellae
      (NTS) (37%) and Streptococcus pneumoniae (30%) were the two commonest isolates.
      Mortality was 18% among general medical admissions and 38% among bacteraemic
      patients. Mortality for individual pathogens was: NTS 33%; S. pneumoniae 36%;
      Escherichia coli 54%; Klebsiella spp. 58%; Neisseria meningitidis 44%; Salmonella
      typhi 17%. Despite an overwhelming association between the major pathogens and
      HIV infection (95% of S. pneumoniae cases and 92% of NTS cases were seropositive
      for HIV), a seasonal pattern was preserved. Streptococcus pneumoniae was more
      frequently isolated in the cold dry months, while STM isolates increased
      following a rise in temperature. A case of bacteraemia with Vibrio cholerae
      (serotype 01) was detected during a cholera outbreak in the rainy season.
      Although S. pneumoniae isolates were relatively susceptible to penicillin (88%)
      and chloramphenicol (74%), S. typhimurium isolates were fully susceptible only to
      chloramphenicol. CONCLUSIONS: This large study confirms the dominance of NTS and
      S. pneumoniae in bacteraemia in an area affected by HIV-1 and allows comparison
      of mortality by individual pathogens. It demonstrates a preserved seasonal
      pattern of bacteraemia for these major pathogens, despite an overwhelming
      association with HIV infection.

PMID- 11243752
TI  - The presence of Nipah virus in respiratory secretions and urine of patients
      during an outbreak of Nipah virus encephalitis in Malaysia.
AB  - OBJECTIVES: To study the excretion of Nipah virus in the upper respiratory
      secretions and urine of infected patients in relation to other clinical features.
      METHODS: Isolation of Nipah virus from the respiratory secretions and urine was
      made in Vero cells and identified by indirect immunofluorescence assay using anti
      Hendra specific hyperimmune mouse ascitic fluid and FITC-conjugated goat anti
      mouse IgG. RESULTS: During the peak outbreak of Nipah virus encephalitis in
      Malaysia, Nipah virus was isolated from the upper respiratory secretions and
      urine in eight of 20 patients who were virologically and/or serologically
      confirmed to be infected with the virus. From these eight patients, Nipah virus
      was isolated from six throat swab specimens, three urine specimens and only one
      nasal swab specimen. The positive virus isolation rate was related to the
      collection of these specimens during the early phase of the illness (P = 0.068).
      The presence of serum anti-Nipah specific IgM appeared to reduce the chance of
      isolating the virus (P = 0.049). There was no significant difference in the
      isolation rate with respect to the age, gender, ethnic group and clinical
      features associated with grave prognosis and mortality outcome of the patients.
      CONCLUSION: This study shows that it is possible to be infected from secretions
      of infected patients, but epidemiological survey on close contacts so far did not
      suggest that human-to-human transmission is common.

PMID- 11243754
TI  - Molecular typing of Candida isolates from patients hospitalized in an intensive
      care unit.
AB  - OBJECTIVES: The aim of our study was the molecular typing of 40 clinical isolates
      of Candida spp. obtained from patients with burns or trauma hospitalized in the
      intensive care unit of a general hospital. METHODS: Isolates were recovered from
      blood, deep trauma, urine, sputum or from environment within a short period of
      time (4 months). The yeasts were identified using commercial yeast identification
      kits as C. albicans (17 isolates), C. tropicalis (16 isolates) and C.
      parapsilosis (10 isolates). The epidemiological relation of the isolates was
      tested with the Random Amplified Polymorphic DNA assay using three or four
      arbitrary chosen primers. RESULTS: All C. albicans isolates presented distinct
      RAPD profiles, C. tropicalis isolates presented both the same and distinct RAPD
      patterns and the C. parapsilosis isolates presented the same RAPD pattern. All
      the environmental isolates were identified as C. parapsilosis and they had the
      same RAPD pattern as C. parapsilosis clinical isolates. Candida parapsilosis
      delineation was confirmed with PFGE. CONCLUSIONS: The colonization/infection with
      C. albicans was endogenous, the C. tropicalis colonization/infection was both
      endogenous and exogenous, and the C. parapsilosis colonization/infection had an
      environmental origin.

PMID- 11243755
TI  - Infection of hepatitis A virus in Japanese haemophiliacs.
AB  - OBJECTIVES: Outbreaks of hepatitis A virus (HAV) infection in haemophiliacs have
      been reported from many countries. The aim of this study was to determine the
      prevalence of hepatitis A virus antibody (HAVAb) in Japanese haemophiliacs.
      METHODS: Sixty-seven male haemophiliacs were recruited for this study of HAV
      infection. We also compared the rate of HAV infection with that of human
      immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis G virus
      (HGV). RESULTS: Fifteen of 67 haemophiliacs (22.4%) were positive for HAVAb.
      Prevalence of HAVAb was significantly higher in haemophiliacs than in Japanese
      normal subjects previously reported (P= 0.0001). Age, alanine aminotransferase
      (ALT), aspartate aminotransferase (AST), total bilirubin and prevalence of HIV,
      HCV, and HGV were not statistically different between HAVAb positive and HAVAb
      negative haemophiliacs. We suggest that the use of clotting factor concentrates
      is closely associated with HAV infection, but HAV infection does not have an
      effect on clinical course. CONCLUSIONS: Administration of clotting factor
      concentrates may increase risk of HAV infection in haemophiliacs.

PMID- 11243756
TI  - The serological and molecular epidemiology of GB virus C/hepatitis G virus
      infection in a hepatitis C and B endemic area.
AB  - OBJECTIVES: To investigate the serological and molecular characteristics of GB
      virus C/hepatitis G virus (GBV-C/HGV) infection in the hepatitis C virus
      (HCV)/hepatitis B virus (HBV)-endemic areas in Taiwan. METHODS: Sera from 200
      residents from Masago, an HCV/HBV-endemic community in Taiwan, and 400 blood
      donors were tested for GBV-C/HGV RNA by using nested reverse transcription
      polymerase chain reaction and for antibodies to GBV-C/HGV E2-protein (anti-E2) by
      an enzyme-linked immunosorbent assay. Phylogenetic analysis of GBV-C/HGV was
      performed. RESULTS: The prevalence of GBV-C/HGV viraemia, anti-E2 and GBV-C/HGV
      exposure among residents of Masago was significantly higher than that among
      donors (17.0%, 25.5% and 39.5% vs. 3.3%, 7.5% and 10.3%, respectively; all P <
      0.0001). In Masago, the prevalence of GBV-C/HGV exposure was significantly higher
      in residents exposed to HCV than in those without HCV exposure (45.8% vs.
      24.1%;P< 0.005). Based on multivariate analyses, HCV viraemia was the only
      significant factor associated with elevated levels of alanine aminotransferase in
      Masago. Phylogenetic analysis showed all 34 GBV-C/HGV isolates from Masago
      clustered within genotype 3. CONCLUSIONS: GBV-C/HGV was highly prevalent in
      Masago, an HCV/HBV-endemic community in Taiwan. HCV viraemia played the most
      important clinical hepatopathic role in the area. Infections with other hepatitis
      viruses did not influence the anti-E2 seroconversion from GBV-C/HGV infections.

PMID- 11243757
TI  - Chronic scalp wound infection due to Rhodococcus equi in an immunocompetent
      patient.
AB  - A case of chronic scalp wound infection due to Rhodococcus equi in an
      immunocompetent individual following heavily contaminated traumatic injury was
      successfully treated by combining antibiotics and surgery. The agents used were
      erythromycin and rifampicin.

PMID- 11243758
TI  - Burkholderia gladioli: recurrent abscesses in a patient with cystic fibrosis.
AB  - We describe a case of an adult patient with cystic fibrosis who developed chronic
      pulmonary infection and multiple episodes of soft tissue abscesses with
      Burkholderia gladioli; this organism should be added to the list of potential
      pathogens for individuals with cystic fibrosis.

PMID- 11243759
TI  - Subcutaneous infection caused by Dirofilaria repens imported to Slovenia.
AB  - A case of human subcutaneous dirofilariasis is presented. A complete nematode
      removed from the tumour in the occipital region of a 61-year-old woman was
      identified, on the basis of its anatomical and histological characteristics, as a
      nongravid adult female of the species Dirofilaria repens. The patient had
      probably been infected on the Canary Islands, Spain, 7 months previously. In the
      future, the clinical and laboratory staff in Slovenia will have to be more alert
      to the possibility of dirofilariasis in patients with subcutaneous tumours,
      particularly in individuals who had travelled to endemic areas several months or
      years before the tumour was detected.

PMID- 11243760
TI  - Candida glabrata infection after total hip arthroplasty.
AB  - Only two incidents of periprosthetic infection due to Candida glabrata have been
      reported in the literature. We report successful treatment of a total hip
      replacement infected with this rare organism by a two-stage revision and
      synergistic combination antifungal therapy with Amphotericin B and 5-Flucytosine.

PMID- 11243761
TI  - Acute cholecystitis caused by Brucella melitensis: case report and review.
AB  - Brucellosis is a common zoonosis in many parts of the world. Human brucellosis is
      a multisystemic disease with a wide range of clinical symptoms. Biliary
      involvement in the form of acute cholecystitis is a very rare manifestation of
      brucellosis. Here we report the case of a 34-year-old male with acute
      cholecystitis caused by Brucella melitensis and review seven other cases. We
      conclude that brucella may have a focal effect on the gallbladder, in the form of
      acute cholecystitis.

PMID- 11243762
TI  - Septic deep vein thrombosis due to Salmonella johannesburg.

PMID- 11243763
TI  - Thrombolysis for acute ischaemic stroke.

PMID- 11243764
TI  - Expression of EGFR-family proteins in the brain: role in development, health and
      disease.

PMID- 11243765
TI  - Thrombolysis in acute ischaemic stroke.

PMID- 11243766
TI  - Angled rigid neuroendoscope for continuous intraoperative visual monitoring:
      technical note.
AB  - We developed and tested a new, angled rigid endoscope as a tool for performing
      continuous visual monitoring during microsurgery. The shaft of the scope is
      angled 110 degrees at its midportion using a prism. We used the scope
      continuously in 30 cases including 15 pituitary tumours, 7 brain tumours, 7
      cerebral aneurysms, and one hemifacial spasm. For pituitary tumours the tip of
      the scope was positioned in the sphenoid sinus or in the cavity formed by tumour
      removal; for cerebral aneurysms it was placed behind the parent artery or the
      aneurysmal neck. Image quality was acceptable for intraoperative monitoring. In
      no case did the neuroendoscope have a deleterious impact on th e proper function
      of the microscope or surgical instruments. This angled rigid scope was more
      effective for intraoperative monitoring than conventional straight scopes.

PMID- 11243767
TI  - A case of atypical idiopathic orbital myositis mimicking neurological disease.
AB  - A 24 year old patient with acute double vision and headache was admitted to our
      clinic. A diagnosis of orbital myositis was confirmed after magnetic resonance
      imaging and orbital echogram. No other clinical manifestations were observed on
      general examination. Since orbital myositis cases with only neurological symptoms
      and without typical visual impairment are not frequent, we decided to present
      this case.

PMID- 11243768
TI  - Reversible delayed leukoencephalopathy following intravenous heroin overdose.
AB  - We present serial neuropsychological, magnetic resonance (MR) imaging and EEG
      changes in a case of widespread CNS myelinopathy due to intravenous heroin
      overdose complicated by a period of prolonged unconsciousness. Following recovery
      from the acute overdose, the subject had the delayed onset of akinetic mutism
      with urinary incontinence. Sequential formal neuro-psychological assessments over
      9 months showed evolution from severe global cerebral dysfunction to moderate
      disturbance of frontal lobe function. Almost complete resolution of diffuse white
      matter signal changes, accompanied by the development of a degree of volume loss,
      was evident on serial MR imaging over the same period, and generalized arrhythmic
      delta-range slowing on the EEG evolved int o a near normal pattern.

PMID- 11243769
TI  - Inverting papilloma of the sphenoid sinus: report of two cases.
AB  - Two patients with sphenoid sinus inverting papilloma who were treated either by
      transcranial or sublabial trans-septal approach are reported. Inverting
      papillomas arising from the sphenoid sinus are exceedingly rare. The clinical and
      neuro-imaging features, as well as surgical treatment, for sphenoid sinus tumours
      are also briefly discussed.

PMID- 11243770
TI  - Spontaneous resolution of a syrinx.
AB  - Syrinx are often related to trauma, tumours or abnormalities of the
      craniocervical junction. Only a few cases of spontaneous resolution have been
      reported in the literature. The authors present a case of spontaneous resolution
      of a cervical syrinx, and analyse the possible physiopathological mechanisms
      leading to resolution. Other similar cases reported in the literature were
      collected and analysed.

PMID- 11243771
TI  - Primary orbito-cranial adenoid cystic carcinoma with torcular metastasis: a case
      report and review of the literature.
AB  - Adenoid cystic carcinoma is a rare neoplasm arising from the exocrine glands such
      as salivary glands, lachrymal glands, upper respiratory tract, breast or uterine
      cervix. Intracranial involvement is commonly from direct skull base involvement,
      although metastasis may rarely be seen. The predisposition of the adenoid cystic
      carcinoma for perineural and perivascular invasion is the prime reason for the
      locally invasive character of the tumour, often extending into the cranium via
      foramina at the skull base. The authors report a case of primary orbito-cranial
      extradural adenoid cystic carcinoma and cranial metastasis away from the primary
      site. This patient initially had a local excision, and later an exenteration of
      the right eye followed by with radiotherapy. Within months she presented with an
      extradural cranial recurrence, distant torcular metastasis without any
      neurological deficit. Craniotomy and radical excision was undertaken as these
      tumours have slow growth rates, and long term survival of the se patients even in
      the presence of local recurrence and metastasis has been well documented.

PMID- 11243772
TI  - Extradural spinal cavernous haemangioma: case report and review of the
      literature.
AB  - Cavernous haemangiomas (cavernomas) are uncommon vascular malformations of the
      central nervous system (CNS). They occur in both sporadic and familial forms and
      may involve any site in the CNS. Spinal cavernomas are less common than
      intracerebral lesion s, and examples in the spinal epidural space are rare. A
      case of a solitary sporadic spinal extradural cavernoma in a 41 year old male
      which presented as progressive lower limb numbness and weakness is reported. The
      literature regarding spinal cavernomas is reviewed and the symptomatology,
      diagnostic evaluation, pathology, management and prognosis of these lesions are
      discussed.

PMID- 11243773
TI  - Idiopathic spinal cord herniation.
AB  - Spinal cord herniation is a rare condition that has become increasingly
      recognised in the last few years. The authors report a case of idiopathic spinal
      cord herniation in a 33 year old woman who presented with progressive Brown
      Sequard syndrome. The diagnosis was made on MR imaging. After repairing the
      herniation the patient made a gradual improvement. Potential causes are
      discussed, including the possible role of dural tethering. In conclusion,
      idiopathic spinal cord herniation is a potentially treat able condition that
      should be more readily diagnosed with increased awareness and newer imaging
      techniques such as high resolution MRI.

PMID- 11243774
TI  - Multiple actinomyces brain abscesses: case report.
AB  - A case of multiple cerebral abscesses caused by actinomyces is reported in a 37
      year old male with mucoepidermoid carcinoma of the right lung. In conjunction
      with penicillin, sulfonamide and erythromycin, the patient underwent stereotactic
      surgery for aspiration of the brain abscesses under (CT). The bacteria,
      considered to originate from the right lung, were identified from the abscess
      material obtained at surgery. Using proper therapy to control infection and
      intracranial pressure is important. A lon g term follow up with frequent
      computerised tomography evaluation has been conducted and the patient outcome has
      been successful recovery.

PMID- 11243776
TI  - Mapping the molecular interface between the sigma(70) subunit of E. coli RNA
      polymerase and T4 AsiA.
AB  - Bacteriophage T4 antisigma protein AsiA (10 kDa) orchestrates a switch from the
      host and early viral transcription to middle viral transcription by binding to
      the sigma(70) subunit of E. coli RNA polymerase. The molecular determinants of
      sigma(70)-AsiA complex formation are not known. Here, we used combinatorial
      peptide chemistry, protein-protein crosslinking, and mutational analysis to study
      the interaction between AsiA and its target, the 33 amino acid residues-long
      sigma(70) peptide containing conserved region 4.2. Many region 4.2 amino acid
      residues contact AsiA, which likely completely occludes the DNA-binding surface
      of region 4.2. Though none of region 4.2 amino acid residues is singularly
      responsible for the very tight interaction with AsiA, sigma(70) Lys593 and Arg596
      which lie outside the putative DNA recognition element of region 4.2, contribute
      the most. In AsiA, the first 20 amino acid residues are both necessary and
      sufficient for interactions with sigma(70). Our results clarify details of
      sigma(70)-AsiA interaction and open the way for engineering AsiA derivatives with
      altered specificities.

PMID- 11243778
TI  - Guiding ribozyme cleavage through motif recognition: the mechanism of cleavage
      site selection by a group ii intron ribozyme.
AB  - The mechanism by which group II introns cleave the correct phosphodiester linkage
      was investigated by studying the reaction of mutant substrates with a ribozyme
      derived from intron ai5gamma. While fidelity was found to be quite high in most
      cases, a single mutation on the substrate (+1C) resulted in a dramatic loss of
      fidelity. When this mutation was combined with a second mutation that induces a
      bulge in the exon binding site 1/intron binding site 1 (EBS1/IBS1) duplex, the
      base-pairing register of the EBS1/IBS1 duplex was shifted and the cleavage site
      moved to a downstream position on the substrate. Conversely, when mismatches were
      incorporated at the EBS1/IBS1 terminus, the duplex was effectively truncated and
      cleavage occurred at an upstream site. Taken together, these data demonstrate
      that the cleavage site of a group II intron ribozyme can be tuned at will by
      manipulating the thermodynamic stability and structure of the EBS1/IBS1 pairing.
      The results are consistent with a model in which the cleavage site is not
      designated through recognition of specific nucleotides (such as the 5'-terminal
      residue of EBS1). Instead, the ribozyme detects a structure at the junction
      between single and double-stranded residues on the bound substrate. This finding
      explains the puzzling lack of phylogenetic conservation in ribozyme and substrate
      sequences near group II intron target sites.

PMID- 11243777
TI  - The Aspergillus nidulans multimeric CCAAT binding complex AnCF is negatively
      autoregulated via its hapB subunit gene.
AB  - Cis-acting CCAAT elements are frequently found in eukaryotic promoter regions.
      Many of them are bound by conserved multimeric complexes. In the fungus
      Aspergillus nidulans the respective complex was designated AnCF (A. nidulans
      CCAAT binding factor). AnCF is composed of at least three subunits designated
      HapB, HapC and HapE. Here, we show that the promoter regions of the hapB genes in
      both A. nidulans and Aspergillus oryzae contain two inversely oriented, conserved
      CCAAT boxes (box alpha and box beta). Electrophoretic mobility shift assays
      (EMSAs) using both nuclear extracts and the purified, reconstituted AnCF complex
      indicated that AnCF binding in vitro to these boxes occurs in a non-mutually
      exclusive manner. Western and Northern blot analyses showed that steady-state
      levels of HapB protein as well as hapB mRNA were elevated in hapC and hapE
      deletion mutants, suggesting a repressing effect of AnCF on hapB expression.
      Consistently, in a hapB deletion background the hapB-lacZ expression level was
      elevated compared with the expression in the wild-type. This was further
      supported by overexpression of hapB using an inducible alcA-hapB construct.
      Induction of alcA-hapB expression strongly repressed the expression of a hapB
      lacZ gene fusion. However, mutagenesis of box beta led to a fivefold reduced
      expression of a hapB-lacZ gene fusion compared with the expression derived from a
      wild-type hapB-lacZ fusion. These results indicate that (i) box beta is an
      important positive cis-acting element in hapB regulation, (ii) AnCF does not
      represent the corresponding positive trans-acting factor and (iii) that AnCF is
      involved in repression of hapB.

PMID- 11243779
TI  - Functional cooperation between topoisomerase I and single strand DNA-binding
      protein.
AB  - Protein-protein interactions play important role in cell biochemistry by
      favorably or adversely influencing major molecular events. In most documented
      cases, the interaction is direct between the partner molecules. Influence of
      activity in the absence of direct physical interaction between DNA transaction
      proteins is another important means of modulation. We show here that single
      strand binding protein stimulates DNA topoisomerase I activity without direct
      protein-protein interactions. The stimulation is specific to topoisomerase I, as
      DNA gyrase activity is unaffected by SSB. We propose that such cases of
      functional collaboration between DNA transaction proteins play important roles in
      vivo.

PMID- 11243780
TI  - Regulatory sequences in sigma 54 localise near the start of DNA melting.
AB  - Transcription initiation by the enhancer-dependent sigma(54) RNA polymerase
      holoenzyme is positively regulated after promoter binding. The promoter DNA
      melting process is subject to activation by an enhancer-bound activator protein
      with nucleoside triphosphate hydrolysis activity. Tethered iron chelate probes
      attached to amino and carboxyl-terminal domains of sigma(54) were used to map
      sigma(54)-DNA interaction sites. The two domains localise to form a centre over
      the -12 promoter region. The use of deletion mutants of sigma(54) suggests that
      amino-terminal and carboxyl-terminal sequences are both needed for the centre to
      function. Upon activation, the relationship between the centre and promoter DNA
      changes. We suggest that the activator re-organises the centre to favour stable
      open complex formation through adjustments in sigma(54)-DNA contact and sigma(54)
      conformation. The centre is close to the active site of the RNA polymerase and
      includes sigma(54) regulatory sequences needed for DNA melting upon activation.
      This contrasts systems where activators recruit RNA polymerase to promoter DNA,
      and the protein and DNA determinants required for activation localise away from
      promoter sequences closely associated with the start of DNA melting.

PMID- 11243781
TI  - Fission yeast nascent polypeptide-associated complex binds to four-way DNA
      junctions.
AB  - The four-way DNA junction (X-junction) is both a central intermediate of
      recombination reactions and, in some cases, a controlling element in
      transcription and the initiation of DNA replication. Many different proteins have
      been found to bind to X-junctions in a structure-specific manner. In some cases,
      this ability only reflects the proteins' general predilection for distorted DNAs
      but in others the interaction is highly specific and usually signifies that the X
      junction is the real target for the protein in vivo. Here we identify the
      Schizosaccharomyces pombe (Sp) nascent polypeptide associated complex (NAC) as a
      potent binder of X-junction DNA. NAC is highly conserved in eukaryotes and has
      reported functions in transcription and the targeting of proteins within the
      cytosol. NAC is composed of alpha and beta subunits. Each SpNAC subunit has the
      capacity to bind X-junction DNA, but optimal binding depends on a heterodimer of
      subunits. Competition assays and binding comparisons using a range of different
      DNA substrates reveal that SpNAC is highly selective for the X-junction
      structure. By comparative gel electrophoresis we show that the X-junction is held
      in its open square conformation when bound by SpNAC. Junction binding is
      inhibited by concentrations of magnesium ions that are sufficient to "stack" the
      X-junction, suggesting that SpNAC recognises only the open junction structure.
      Finally, SpNAC can bind to X-junctions that are already bound by a tetramer of
      the Escherichia coli RuvA protein, indicating that it interacts with only one
      face of the junction. The possible biological significance of X-junction binding
      by SpNAC is discussed.

PMID- 11243782
TI  - Identification of muscle specific ring finger proteins as potential regulators of
      the titin kinase domain.
AB  - The giant myofibrillar protein titin contains within its C-terminal region a
      serine-threonine kinase of unknown function. We have identified a novel muscle
      specific RING finger protein, referred to as MURF-1, that binds in vitro to the
      titin repeats A168/A169 adjacent to the titin kinase domain. In myofibrils, MURF
      1 is present within the periphery of the M-line lattice in close proximity to
      titin's catalytic kinase domain, within the Z-line lattice, and also in soluble
      form within the cytoplasm. Yeast two-hybrid screens with MURF-1 as a bait
      identified two other highly homologous MURF proteins, MURF-2 and MURF-3. MURF
      1,2,3 proteins are encoded by distinct genes, share highly conserved N-terminal
      RING domains and in vitro form dimers/heterodimers by shared coiled-coil motifs.
      Of the MURF family, only MURF-1 interacts with titin repeats A168/A169, whereas
      MURF-3 has been reported to affect microtubule stability. Association of MURF-1
      with M-line titin may potentially modulate titin's kinase activity similar to
      other known kinase-associated proteins, whereas differential expression and
      heterodimerization of MURF1, 2 and 3 may link together titin kinase and
      microtubule-dependent signal pathways in striated muscles.

PMID- 11243783
TI  - pH-induced structural changes regulate histidine decarboxylase activity in
      Lactobacillus 30a.
AB  - Histidine decarboxylase (HDC) from Lactobacillus 30a produces histamine that is
      essential to counter waste acids, and to optimize cell growth. The HDC trimer is
      active at low pH and inactive at neutral to alkaline pH. We have solved the X-ray
      structure of HDC at pH 8 and revealed the novel mechanism of pH regulation. At
      high pH helix B is unwound, destroying the substrate binding pocket. At acid pH
      the helix is stabilized, partly through protonation of Asp198 and Asp53 on either
      side of the molecular interface, acting as a proton trap. In contrast to
      hemoglobin regulation, pH has a large effect on the tertiary structure of HDC
      monomers and relatively little or no effect on quaternary structure.

PMID- 11243784
TI  - Transthyretin stability as a key factor in amyloidogenesis: X-ray analysis at
      atomic resolution.
AB  - Transthyretin (TTR) amyloidosis is a conformational disturbance, which, like
      other amyloidoses, represents a life threat. Here, we report a TTR variant, TTR
      Thr119Met, that has been shown to have a protective role in the development of
      clinical symptoms in carriers of TTR Val30Met, one of the most frequent variants
      among TTR amyloidosis patients. In order to understand this effect, we have
      determined the structures of the TTR Val30Met/Thr119Met double mutant isolated
      from the serum of one patient and of both the native and thyroxine complex of TTR
      Thr119Met. Major conclusions are: (i) new H-bonds within each monomer and monomer
      monomer inter-subunit contacts, e.g. Ser117-Ser117 and Met119-Tyr114, increase
      protein stability, possibly leading to the protective effect of the TTR
      Val30Met/Thr119Met variant when compared to the single variant TTR Val30Met. (ii)
      The mutated residue (Met119) extends across the thyroxine binding channel
      inducing conformational changes that lead to closer contacts between different
      dimers within the tetramer. The data, at atomic resolution, were essential to
      detect, for the first time, the subtle changes in the inter-subunit contacts of
      TTR, and explain the non-amyloidogenic potential of the TTR Thr119Met variant,
      improving considerably current research on the TTR amyloid fibril formation
      pathway.

PMID- 11243785
TI  - Tiny TIM: a small, tetrameric, hyperthermostable triosephosphate isomerase.
AB  - Comparative structural studies on proteins derived from organisms with growth
      optima ranging from 15 to 100 degrees C are beginning to shed light on the
      mechanisms of protein thermoadaptation. One means of sustaining
      hyperthermostability is for proteins to exist in higher oligomeric forms than
      their mesophilic homologues. Triosephosphate isomerase (TIM) is one of the most
      studied enzymes, whose fold represents one of nature's most common protein
      architectures. Most TIMs are dimers of approximately 250 amino acid residues per
      monomer. Here, we report the 2.7 A resolution crystal structure of the extremely
      thermostable TIM from Pyrococcus woesei, a hyperthermophilic archaeon growing
      optimally at 100 degrees C, representing the first archaeal TIM structure. P.
      woesei TIM exists as a tetramer comprising monomers of only 228 amino acid
      residues. Structural comparisons with other less thermostable TIMs show that
      although the central beta-barrel is largely conserved, severe pruning of several
      helices and truncation of some loops give rise to a much more compact monomer in
      the small hyperthermophilic TIM. The classical TIM dimer formation is conserved
      in P. woesei TIM. The extreme thermostability of PwTIM appears to be achieved by
      the creation of a compact tetramer where two classical TIM dimers interact via an
      extensive hydrophobic interface. The tetramer is formed through largely
      hydrophobic interactions between some of the pruned helical regions. The
      equivalent helical regions in less thermostable dimeric TIMs represent regions of
      high average temperature factor. The PwTIM seems to have removed these regions of
      potential instability in the formation of the tetramer. This study of PwTIM
      provides further support for the role of higher oligomerisation states in extreme
      thermal stabilisation.

PMID- 11243786
TI  - Crystal structure of GerE, the ultimate transcriptional regulator of spore
      formation in Bacillus subtilis.
AB  - The small, DNA-binding protein GerE regulates gene transcription in the
      terminally differentiated mother-cell compartment during late stages of
      sporulation in Bacillus subtilis. This versatile transcription factor shares
      sequence homology with the LuxR/FixJ/UhpA family of activators and modulates the
      expression of a number of genes, in particular those encoding the components of
      the coat that surrounds the mature spore. GerE orchestrates the final stages of
      coat deposition and maturation that lead to a spore with remarkable resistance
      properties but that must be responsive to low levels of germination signals. As
      this germination process is largely passive and can occur in the absence of de
      novo protein synthesis, the correct assembly of germination machinery, including
      germinant receptors and energy storage compounds, is crucial to the survival of
      the cell. The crystal structure of GerE has been solved at 2.05 A resolution
      using multi-wavelength anomalous dispersion techniques and reveals the nature of
      the GerE dimer. Each monomer comprises four alpha-helices, of which the central
      pair forms a helix-turn-helix DNA-binding motif. Implications for DNA-binding and
      the structural organisation of the LuxR/FixJ/UhpA family of transcription
      activator domains are discussed.

PMID- 11243787
TI  - Divide-and-conquer crystallographic approach towards an atomic structure of
      intermediate filaments.
AB  - Intermediate filaments (IFs) represent an essential component of the cytoskeleton
      in higher eukaryotic cells. The elementary building block of the IF architecture
      is an elongated dimer with its dominant central part being a parallel double
      stranded alpha-helical coiled coil. Filament formation proceeds via a specific
      multi-step association of the dimers into the unit-length filaments, which
      subsequently anneal longitudinally and finally radially compact into mature
      filaments. To tackle the challenge of a crystallographic structure determination,
      we have produced and characterised 17 overlapping soluble fragments of human IF
      protein vimentin. For six fragments ranging in length between 39 and 84 amino
      acid residues, conditions yielding macroscopic crystals could be established and
      X-ray diffraction data were collected to the highest resolution limit between 1.4
      and 3 A. We expect that solving the crystal structures of these and further
      fragments will eventually allow us to patch together a molecular model for the
      full-length vimentin dimer. This divide-and-conquer approach will be subsequently
      extended to determining the crystal structures of a number of complexes formed by
      appropriate vimentin fragments, and will eventually allow us to establish the
      three- dimensional architecture of complete filaments at atomic resolution.

PMID- 11243788
TI  - Structural analysis of the N-terminal domain of the human T-cell leukemia virus
      capsid protein.
AB  - The N-terminal domain of the retroviral capsid (CA) protein is one of the least
      conserved regions encoded in the genome. Surprisingly, the three-dimensional
      structures of the CA from different genera exhibit alpha-helical structural
      features that are highly conserved. The N-terminal residues of the human
      immunodeficiency virus type 1 (HIV-1) and Rous sarcoma virus (RSV) capsid
      proteins form a beta-hairpin. To determine if this feature is conserved in the
      retroviral family, we cloned, expressed, purified, and solved the structure of a
      N-terminal 134 amino acid fragment (CA(134)) from the human T-cell leukemia virus
      type 1 (HTLV-I) using high resolution nuclear magnetic resonance (NMR)
      spectroscopy. The CA(134) fragment contains an N-terminal beta-hairpin and a
      central coiled-coil-like structure composed of six alpha-helices. The N-terminal
      Pro1 residue contacts Asp54 in the helical cluster through a salt bridge. Thus,
      the beta-hairpin is conserved and the helical cluster is structurally similar to
      other retroviral CA domains. However, although the same Asp residue defines the
      orientation of the hairpin in both the HTLV-1 and HIV-1 CA proteins, the HTLV-I
      hairpin is oriented away, rather than towards, the helical core. Significant
      differences were also detected in the spatial orientation and helical content of
      the long centrally located loop connecting the helices in the core. It has been
      proposed that the salt bridge allows the formation of a CA-CA interface that is
      important for the assembly of the conical cores that are characteristic of HIV-1.
      As HTLV-I forms spherical cores, the salt-bridge feature is apparently not
      conserved for this function although its role in determining the orientation of
      the beta-hairpin may be critical, along with the central loop. Comparison of
      three-dimensional structures is expected to elucidate the relationships between
      the retroviral capsid protein structure and its function.

PMID- 11243789
TI  - The Bowman-Birk inhibitor reactive site loop sequence represents an independent
      structural beta-hairpin motif.
AB  - We have determined the NMR structure in aqueous solution of a disulphide-cyclised
      11-residue peptide that forms a stable beta-hairpin, incorporating a type VIb
      beta-turn. The structure is found to be extremely well ordered for a short
      peptide, with the 30 lowest energy simulated annealing structures having an
      average pairwise r.m.s. deviation of only 0.36 A over the backbone. All but three
      side-chains adopt distinct conformations, allowing a detailed analysis of their
      involvement in cross-strand interactions. The peptide sequence analysed
      originates from a previously reported study, which identified potent inhibitors
      of human leukocyte elastase from screening a combinatorial peptide library based
      on the short protein beta-sheet segment that forms the reactive site loop of
      Bowman-Birk inhibitors. A detailed comparison of the peptide's solution structure
      with the corresponding region in the whole protein structure reveals a very good
      correspondence not only for the backbone (r.m.s. deviation approximately 0.7 A)
      but also for the side-chains. This isolated beta-hairpin retains the biologically
      active "canonical conformation" typical of small serine proteinase inhibitor
      proteins, which explains why it retains inhibitory activity. Since the structural
      integrity is sequence-inherent and does not depend upon the presence of the
      remaining protein, this beta-hairpin represents an independent structural motif
      and so provides a useful model of this type of protein architecture and its
      relation to biological function. The relationship between the conformation of
      this beta-hairpin and its biological activity is discussed.

PMID- 11243790
TI  - Folding energetics of ligand binding proteins. I. Theoretical model.
AB  - Heat capacity curves as obtained from differential scanning calorimetry are an
      outstanding source for molecular information on protein folding and ligand
      binding energetics. However, deconvolution of C(p) data of proteins in the
      presence of ligands can be compromised by indeterminacies concerning the correct
      choice of the statistical thermodynamic ensemble. By convent, the assumption of
      constant free ligand concentration has been used to derive formulae for the
      enthalpy. Unless the ligand occurs at large excess, this assumption is incorrect.
      Still the relevant ensemble is the grand canonical ensemble. We derive formulae
      for both constraints, constancy of total or free ligand concentration and
      illustrate the equations by application to the typical equilibrium Nx <=> N + x
      <=> D + x. It is demonstrated that as long as the thermodynamic properties of the
      ligand can be completely corrected for by performing a reference measurement, the
      grand canonical approach provides the proper and mathematically significantly
      simpler choice. We demonstrate on the two cases of sequential or independent
      ligand-binding the fact, that similar binding mechanisms result in different and
      distinguishable heat capacity equations. Finally, we propose adequate strategies
      for DSC experiments as well as for obtaining first estimates of the
      characteristic thermodynamic parameters, which can be used as starting values in
      a global fit of DSC data.

PMID- 11243791
TI  - Folding energetics of ligand binding proteins II. Cooperative binding of Ca2+ to
      annexin I.
AB  - The calcium binding properties of annexin I as observed by thermodynamic DSC
      studies have been compared to the structural information obtained from X-ray
      investigation. The calorimetric experiment permitted to evaluate both the
      reaction scheme - including binding of ligand and conformational changes - and
      the energetics of each reaction step. According to published X-ray data Annexin I
      has six calcium binding sites, three medium-affinity type II and three low
      affinity type III sites. The present study shows that at 37 degrees C annexin I
      binds in a Hill type fashion simultaneously two calcium ions in a first step with
      medium affinity at a concentration of 0.6 mM and another three Ca(2+) ions again
      cooperatively at 30 mM with low affinity. Therefore it can be concluded that only
      two medium-affinity type II binding sites are available. The third site, that
      should be accessible in principle appears to be masked presumably due to the
      presence of the N terminus. In view of the large calcium concentration needed for
      saturation of the binding sites, annexin I may be expected to be Ca(2+) free in
      vivo unless other processes such as membrane interaction occur simultaneously.
      This assumption is consistent with the finding, that the affinity of annexins to
      calcium is usually markedly increased by the presence of lipids.

PMID- 11243792
TI  - Native topology or specific interactions: what is more important for protein
      folding?
AB  - Fifty-five molecular dynamics runs of two three-stranded antiparallel beta-sheet
      peptides were performed to investigate the relative importance of amino acid
      sequence and native topology. The two peptides consist of 20 residues each and
      have a sequence identity of 15 %. One peptide has Gly-Ser (GS) at both turns,
      while the other has d-Pro-Gly ((D)PG). The simulations successfully reproduce the
      NMR solution conformations, irrespective of the starting structure. The large
      number of folding events sampled along the trajectories at 360 K (total
      simulation time of about 5 micros) yield a projection of the free-energy
      landscape onto two significant progress variables. The two peptides have compact
      denatured states, similar free-energy surfaces, and folding pathways that involve
      the formation of a beta-hairpin followed by consolidation of the unstructured
      strand. For the GS peptide, there are 33 folding events that start by the
      formation of the 2-3 beta-hairpin and 17 with first the 1-2 beta-hairpin. For the
      (D)PG peptide, the statistical predominance is opposite, 16 and 47 folding events
      start from the 2-3 beta-hairpin and the 1-2 beta-hairpin, respectively. These
      simulation results indicate that the overall shape of the free-energy surface is
      defined primarily by the native-state topology, in agreement with an ever
      increasing amount of experimental and theoretical evidence, while the amino acid
      sequence determines the statistically predominant order of the events.

PMID- 11243793
TI  - Catalytic efficiency and sequence selectivity of a restriction endonuclease
      modulated by a distal manganese ion binding site.
AB  - Crystal structures of EcoRV endonuclease bound in a ternary complex with cognate
      duplex DNA and manganese ions have previously revealed an Mn(2+)-binding site
      located between the enzyme and the DNA outside of the dyad-symmetric GATATC
      recognition sequence. In each of the two enzyme subunits, this metal ion bridges
      between a distal phosphate group of the DNA and the imidazole ring of His71. The
      new metal- binding site is specific to Mn(2+) and is not occupied in ternary
      cocrystal structures with either Mg(2+) or Ca(2+). Characterization of the H71A
      and H71Q mutants of EcoRV now demonstrates that these distal Mn(2+) sites
      significantly modulate activity toward both cognate and non-cognate DNA
      substrates. Single-turnover and steady-state kinetic analyses show that removal
      of the distal site in the mutant enzymes increases Mn(2+)-dependent cleavage
      rates of specific substrates by tenfold. Conversely, the enhancement of non
      cognate cleavage at GTTATC sequences by Mn(2+) is significantly attenuated in the
      mutants. As a consequence, under Mn(2+) conditions EcoRV-H71A and EcoRV-H71Q are
      100 to 700-fold more specific than the wild-type enzyme for cognate DNA relative
      to the GTTATC non-cognate site. These data reveal a strong dependence of DNA
      cleavage efficiency upon metal ion-mediated interactions located some 20 A
      distant from the scissile phosphodiester linkages. They also show that
      discrimination of cognate versus non-cognate DNA sequences by EcoRV depends in
      part on contacts with the sugar-phosphate backbone outside of the target site.

PMID- 11243794
TI  - How methionyl-tRNA synthetase creates its amino acid recognition pocket upon L
      methionine binding.
AB  - Amino acid selection by aminoacyl-tRNA synthetases requires efficient mechanisms
      to avoid incorrect charging of the cognate tRNAs. A proofreading mechanism
      prevents Escherichia coli methionyl-tRNA synthetase (EcMet-RS) from activating in
      vivo L-homocysteine, a natural competitor of L-methionine recognised by the
      enzyme. The crystal structure of the complex between EcMet-RS and L-methionine
      solved at 1.8 A resolution exhibits some conspicuous differences with the
      recently published free enzyme structure. Thus, the methionine delta-sulphur atom
      replaces a water molecule H-bonded to Leu13N and Tyr260O(eta) in the free enzyme.
      Rearrangements of aromatic residues enable the protein to form a hydrophobic
      pocket around the ligand side-chain. The subsequent formation of an extended
      water molecule network contributes to relative displacements, up to 3 A, of
      several domains of the protein. The structure of this complex supports a
      plausible mechanism for the selection of L-methionine versus L-homocysteine and
      suggests the possibility of information transfer between the different functional
      domains of the enzyme.

PMID- 11243795
TI  - Native hydrogen bonds in a molten globule: the apoflavodoxin thermal
      intermediate.
AB  - The structure and energetics of protein-folding intermediates are poorly
      understood. We have identified, in the thermal unfolding of the apoflavodoxin
      from Anabaena PCC 7119, an equilibrium intermediate with spectroscopic properties
      of a molten globule and substantial enthalpy and heat capacity of unfolding. The
      structure of the intermediate is probed by mutagenesis (and phi analysis) of
      polar residues involved in surface-exposed hydrogen bonds connecting secondary
      structure elements in the native protein. All hydrogen bonds analysed are formed
      in the molten globule intermediate, either with native strength or debilitated.
      This suggests the overall intermediate's topology and surface tertiary
      interactions are close to native, and indicates that hydrogen bonding may
      contribute significantly to shape the conformation and energetics of folding
      intermediates.

PMID- 11243796
TI  - The chaperone function of ClpB from Thermus thermophilus depends on allosteric
      interactions of its two ATP-binding sites.
AB  - ClpB belongs to the Hsp100 family and assists de-aggregation of protein
      aggregates by DnaK chaperone systems. It contains two Walker consensus sequences
      (or P-Loops) that indicate potential nucleotide binding domains (NBD). Both
      domains appear to be essential for chaperoning function, since mutation of the
      conserved lysine residue of the GX(4)GKT consensus sequences to glutamine (K204Q
      and K601Q) abolishes its properties to accelerate renaturation of aggregated
      firefly luciferase. The underlying biochemical reason for this malfunction
      appears not to be a dramatically reduced ATPase activity of either P-loop per se
      but rather changed properties of co-operativity of ATPase activity connected to
      oligomerization properties to form productive oligomers. This view is
      corroborated by data that show that structural stability (as judged by CD
      spectroscopy) or ATPase activity at single turnover conditions (at low ATP
      concentrations) are not significantly affected by these mutations. In addition
      nucleotide binding properties of wild-type protein and mutants (as judged by
      binding studies with fluorescent nucleotide analogues and competitive
      displacement titrations) do not differ dramatically. However, the general pattern
      of formation of stable, defined oligomers formed as a function of salt
      concentration and nucleotides and more importantly, cooperativity of ATPase
      activity at high ATP concentrations is dramatically changed with the two P-loop
      mutants described.

PMID- 11243797
TI  - Crystal structure of the catalytic core component of the alkylhydroperoxide
      reductase AhpF from Escherichia coli.
AB  - Alkylhydroperoxide reductases (AhpR, EC 1.6.4.*) are essential for the oxygen
      tolerance of aerobic organisms by converting otherwise toxic hydroperoxides of
      lipids or nucleic acids to the corresponding alcohols. The AhpF component belongs
      to the family of pyridine nucleotide-disulphide oxidoreductases and channels
      electrons from NAD(P)H towards the AhpC component which finally reduces cognate
      substrates. The structure of the catalytic core of the Escherichia coli AhpF
      (A212-A521) with a bound FAD cofactor was determined at 1.9 A resolution in its
      oxidized state. The dimeric arrangement of the AhpF catalytic core and the
      predicted interaction mode between the N-terminal PDO-like domain and the NADPH
      domain favours an intramolecular electron transfer between the two redox-active
      disulphide centres of AhpF.

PMID- 11243798
TI  - Crystal structure of alginate lyase A1-III complexed with trisaccharide product
      at 2.0 A resolution.
AB  - The structure of A1-III from a Sphingomonas species A1 complexed with a
      trisaccharide product (4-deoxy-l-erythro-hex-4-enepyranosyluronate-mannuronate
      mannuronic acid) was determined by X-ray crystallography at 2.0 A with an R
      factor of 0.16. The final model of the complex form comprising 351 amino acid
      residues, 245 water molecules, one sulfate ion and one trisaccharide product
      exhibited a C(alpha) r.m.s.d. value of 0.154 A with the reported apo form of the
      enzyme. The trisaccharide was bound in the active cleft at subsites -3
      approximately -1 from the non-reducing end by forming several hydrogen bonds and
      van der Waals interactions with protein atoms. The catalytic residue was
      estimated to be Tyr246, which existed between subsites -1 and +1 based on a
      mannuronic acid model oriented at subsite +1.

PMID- 11243799
TI  - The UBX domain: a widespread ubiquitin-like module.
AB  - The UBX domain is an 80 amino acid residue module that is present typically at
      the carboxyl terminus of a variety of eukaryotic proteins. In an effort to
      elucidate the function of UBX domains, we solved the three-dimensional structure
      of the UBX domain of human Fas-associated factor-1 (FAF1) by NMR spectroscopy.
      The structure has a beta-Grasp fold characterised by a beta-beta-alpha-beta-beta
      alpha-beta secondary-structure organisation. The five beta strands are arranged
      into a mixed sheet in the order 21534. The longer first helix packs across the
      first three strands of the sheet, and a second shorter 3(10) helix is located in
      an extended loop connecting strands 4 and 5. In the absence of significant
      sequence similarity, the UBX domain can be superimposed with ubiquitin with an
      r.m.s.d. of 1.9 A, suggesting that the two structures share the same superfold,
      and an evolutionary relationship. However, the absence of a carboxyl-terminal
      extension containing a double glycine motif and of suitably positioned lysine
      side-chains makes it highly unlikely that UBX domains are either conjugated to
      other proteins or part of mixed UBX-ubiquitin chains. Database searches revealed
      that most UBX domain-containing proteins belong to one of four evolutionarily
      conserved families represented by the human FAF1, p47, Y33K, and Rep8 proteins. A
      role of the UBX domain in ubiquitin-related processes is suggested.

PMID- 11243800
TI  - Differential melting of the transcription start site associated with changes in
      RNA polymerase-promoter contacts in initiating transcription complexes.
AB  - Formaldehyde cross-linking was used in a kinetic analysis of RNA polymerase
      lacUV5 promoter interactions in open complexes (RP(o)). RP(o) quenched from 37
      degrees C to 14 degrees C isomerised to a closed, competitor resistant, complex
      (RP(LT)). We observed that contacts of the beta' and sigma subunits with the
      positions -3, -5 of the non-template DNA strand disappeared very quickly during
      the first 30 seconds after the temperature downshift. The re-annealing of the DNA
      downstream of the transcription start site takes place in the same time scale.
      However re-annealing of the upstream part of the transcription bubble was slower
      and completed within five minutes. The results support a two-step model of
      promoter melting and suggest that conformational changes in the RNA polymerase
      occur concurrently with the melting around the transcription start site.

PMID- 11243801
TI  - Mh1 domain of Smad is a degraded homing endonuclease.
AB  - Smad proteins are eukarytic transcription regulators in the TGF-beta signaling
      cascade. Using a combination of sequence and structure-based analyses, we argue
      that MH1 domain of Smad is homologous to the diverse His-Me finger endonuclease
      family enzymes. The similarity is particularly extensive with the I-PpoI
      endonuclease. In addition to the global fold similarities, both proteins possess
      a conserved motif of three cysteine residues and one histidine residue which form
      a zinc-binding site in I-PpoI. Sequence and structure conservation in the motif
      region strongly suggest that MH1 domain may also incorporate a metal ion in its
      structural core. MH1 of Smad3 and I-PpoI exhibit similar nucleic acid binding
      mode and interact with DNA major groove through an antiparallel beta-sheet. MH1
      is an example of transcription regulator derived from the ancient enzymatic
      domain that lost its catalytic activity but retained DNA-binding sites.

PMID- 11243802
TI  - Modulation of transcription reveals a new mechanism of triplet repeat instability
      in Escherichia coli.
AB  - Many human hereditary disease genes are associated with the expansion of triplet
      repeat sequences. In Escherichia coli (CTG/CAG) triplet repeat sequences are
      unstable and we have developed a plasmid-based assay enabling us to observe and
      quantify both expansions and deletions. In this work, we have investigated the
      role of transcription on the instability of a (CTG/CAG) insert containing 64
      repeats. Using this assay, we show that induction of transcription results in a
      significant increase in the frequency of long deletions and a reduction in the
      frequency of long expansions. On the other hand, overproduction of transcription
      repressor molecules leads to an increase in both expansions and deletions. In
      this latter case, we propose that the increased instability is due to the arrest
      of replication progression by the interaction of the repressor molecule with its
      cognate operator and subsequent generations of DNA strand breaks.

PMID- 11243803
TI  - The hairpin ribozyme substrate binding-domain: a highly constrained D-shaped
      conformation.
AB  - The two domains of the hairpin ribozyme-substrate complex, usually depicted as
      straight structural elements, must interact with one another in order to form an
      active conformation. Little is known about the internal geometry of the
      individual domains in an active docked complex. Using various crosslinking and
      structural approaches in conjunction with molecular modeling (constraint
      satisfaction program MC-SYM), we have investigated the conformation of the
      substrate-binding domain in the context of the active docked ribozyme-substrate
      complex. The model generated by MC-SYM showed that the domain is not straight but
      adopts a bent conformation (D-shaped) in the docked state of the ribozyme,
      indicating that the two helices bounding the internal loop are closer than was
      previously assumed. This arrangement rationalizes the observed ability of hairpin
      ribozymes with a circularized substrate-binding strand to cleave a circular
      substrate, and provides essential information concerning the organization of the
      substrate in the active conformation. The internal geometry of the substrate
      binding strand places G8 of the substrate-binding strand near the cleavage site,
      which has allowed us to predict the crucial role played by this nucleotide in the
      reaction chemistry.

PMID- 11243804
TI  - Structural isomers of bis-PNA bound to a target in duplex DNA.
AB  - Upon binding of a decamer bis-PNA (H-Lys-TTCCTCTCTT-(eg1)(3)-TTCTCTCCTT-LysNH(2))
      to a complementary target in a double-stranded DNA fragment, three distinct
      complexes were detected by gel mobility shift analysis. Using in situ chemical
      probing techniques (KMnO(4) and DMS) it was found that all three complexes
      represent bona fide sequence-specific PNA binding to the designated target, but
      the complexes were structurally different. One complex that preferentially formed
      at higher PNA concentrations contains two bis-PNA molecules per DNA target,
      whereas the other two complexes are genuine triplex invasion clamped structures.
      However, these two latter complexes differ by the path relative to the DNA target
      of the flexible ethylene-glycol linker connecting the two PNA oligomers that
      comprise a bis-PNA. We distinguish between one in which the linker wraps around
      the non-target DNA strand, thus making this strand part of the triplex invasion
      complex and another complex that encompass the target strand only. The
      implications of these results are discussed in terms of DNA targeting by
      synthetic ligands.

PMID- 11243805
TI  - Function of the Neurospora crassa mitochondrial tyrosyl-tRNA synthetase in RNA
      splicing. Role of the idiosyncratic N-terminal extension and different modes of
      interaction with different group I introns.
AB  - The Neurospora crassa mitochondrial tyrosyl-tRNA synthetase (CYT-18 protein)
      promotes the splicing of group I introns by helping the intron RNA fold into the
      catalytically active structure. The regions required for splicing include an
      idiosyncratic N-terminal extension, the nucleotide-binding fold domain, and the C
      terminal RNA-binding domain. Here, we show that the idiosyncratic N-terminal
      region is in fact comprised of two functionally distinct parts: an upstream
      region consisting predominantly of a predicted amphipathic alpha-helix (H0),
      which is absent from bacterial tyrosyl-tRNA synthetases (TyrRSs), and a
      downstream region, which contains predicted alpha-helices H1 and H2,
      corresponding to features in the X-ray crystal structure of the Bacillus
      stearothermophilus TyrRS. Bacterial genetic assays with libraries of CYT-18
      mutants having random mutations in the N-terminal region identified functionally
      important amino acid residues and supported the predicted structures of the H0
      and H1 alpha-helices. The function of N and C-terminal domains of CYT-18 was
      investigated by detailed biochemical analysis of deletion mutants. The results
      confirmed that the N-terminal extension is required only for splicing activity,
      but surprisingly, at least in the case of the N. crassa mitochondrial (mt) large
      ribosomal subunit (LSU) intron, it appears to act primarily by stabilizing the
      structure of another region that interacts directly with the intron RNA. The
      H1/H2 region is required for splicing activity and TyrRS activity with the N.
      crassa mt tRNA(Tyr), but not for TyrRS activity with Escherichia coli tRNA(Tyr),
      implying a somewhat different mode of recognition of the two tyrosyl-tRNAs.
      Finally, a CYT-18 mutant lacking the N-terminal H0 region is totally defective in
      binding or splicing the N. crassa ND1 intron, but retains substantial residual
      activity with the mt LSU intron, and conversely, a CYT-18 mutant lacking the C
      terminal RNA-binding domain is totally defective in binding or splicing the mt
      LSU intron, but retains substantial residual activity with the ND1 intron. These
      findings lead to the surprising conclusion that CYT-18 promotes splicing via
      different sets of interactions with different group I introns. We suggest that
      these different modes of promoting splicing evolved from an initial interaction
      based on the recognition of conserved tRNA-like structural features of the group
      I intron catalytic core.

PMID- 11243806
TI  - The hydH/G Genes from Escherichia coli code for a zinc and lead responsive two
      component regulatory system.
AB  - The hydH/G genes from Escherichia coli code for a two-component regulatory system
      that has been implicated in the regulation of hydrogenase 3 formation. In a
      detailed study of the function of HydH/G employing hycA'-'lacZ reporter gene
      fusions, it was shown that HydH/G indeed led to a stimulation of activation of
      the hycA promoter responsible for hydrogenase 3 synthesis but only when hydG is
      overexpressed from a plasmid in a strain lacking FhlA. Since the stimulation was
      not observed with an fdhF'-'lacZ fusion, and since it was independent from a
      functional hydH gene product, it must be considered as unspecific cross-talk. An
      extensive search for the actual physiological signal of HydH/G showed that the
      system responds to high concentrations of zinc or lead in the medium. Expression
      of zraP, a gene inversely oriented to hydH/G whose product seems to be involved
      in acquisition of tolerance to high Zn(2+) concentrations, is stimulated by high
      Zn(2+) and Pb(2+) concentrations and this stimulation requires both HydH and
      HydG. Purified HydG in the presence of phosphoryl donors binds to a region within
      the zraP-hydHG intergenic region that is characterised by two inverted repeats
      separated by a 14 bp spacer. Putative -12/-24 sigma(54)-dependent promoter motifs
      are present upstream of both the zraP and the hydHG transcriptional units; in
      accordance, transcription of zraP is strictly dependent on the presence of a
      functional rpoN gene. The expression of hydH/G is autoregulated: high Zn(2+) and
      Pb(2+) concentrations lead to a significant increase of the HydG protein content
      which took place only in a hydH(+) genetic background. Since HydH binds to
      membranes tightly, it is assumed that the HydH/G system senses high periplasmic
      Zn(2+) and Pb(2+) concentrations and contributes to metal tolerance by activating
      the expression of zraP. The redesignation of hydH/G as zraS/R is suggested.

PMID- 11243808
TI  - Determinants of chemotactic signal amplification in Escherichia coli.
AB  - A well-characterized protein phosphorelay mediates Escherichia coli chemotaxis
      towards the amino acid attractant aspartate. The protein CheY shuttles between
      flagellar motors and methyl-accepting chemoreceptor (MCP) complexes containing
      the linker CheW and the kinase CheA. CheA-CheY phosphotransfer generates phospho
      CheY, CheY-P. Aspartate triggers smooth swim responses by inactivation of the
      CheA bound to the target MCP, Tar; but this mechanism alone cannot explain the
      observed response sensitivity. Here, we used behavioral analysis of mutants
      deleted for CheZ, a catalyst of CheY-P dephosphorylation, or the
      methyltransferase CheR and/or the methylesterase CheB to examine the roles of
      accelerated CheY-P dephosphorylation and MCP methylation in enhancement of the
      chemotactic response. The extreme motile bias of the mutants was adjusted towards
      wild-type values, while preserving much of the aspartate response sensitivity by
      expressing fragments of the MCP, Tsr, that either activate or inhibit CheA. We
      then measured responses to small jumps of aspartate, generated by flash
      photolysis of photo-labile precursors. The stimulus-response relation for Delta
      cheZ mutants overlapped that for the host strains. Delta cheZ excitation response
      times increased with stimulus size consistent with formation of an occluded CheA
      state. Thus, neither CheZ-dependent or independent increases in CheY-P
      dephosphorylation contribute to the excitation response. In Delta cheB Delta cheR
      or Delta cheR mutants, the dose for a half-maximal response, [Asp](50), was ca 10
      microM; but was elevated to 100 microM in Delta cheB mutants. In addition, the
      stimulus-response relation for these mutants was linear, consistent with
      stoichiometric inactivation, in contrast to the non-linear relation for wild-type
      E. coli. These data suggest that response sensitivity is controlled by
      differential binding of CheR and/or CheB to distinct MCP signaling conformations.

PMID- 11243807
TI  - Molecular, genetic and physiological characterisation of dystrobrevin-like (dyb
      1) mutants of Caenorhabditis elegans.
AB  - Dystrobrevins are protein components of the dystrophin complex, whose disruption
      leads to Duchenne muscular dystrophy and related diseases. The Caenorhabditis
      elegans dystrobrevin gene (dyb-1) encodes a protein 38 % identical with its
      mammalian counterparts. The C. elegans dystrobrevin is expressed in muscles and
      neurons. We characterised C. elegans dyb-1 mutants and showed that: (1) their
      behavioural phenotype resembles that of dystrophin (dys-1) mutants; (2) the
      phenotype of dyb-1 dys-1 double mutants is not different from the single ones;
      (3) dyb-1 mutants are more sensitive than wild-type animals to reductions of
      acetylcholinesterase levels and have an increased response to acetylcholine; (4)
      dyb-1 mutations alone do not lead to muscle degeneration, but synergistically
      produce a progressive myopathy when combined with a mild MyoD/hlh-1 mutation. All
      together, these findings further substantiate the role of dystrobrevins in
      cholinergic transmission and as functional partners of dystrophin.

PMID- 11243809
TI  - Calcium-dependent structural changes in scallop heavy meromyosin.
AB  - The mechanism of calcium regulation of scallop myosin is not understood, although
      it is known that both myosin heads are required. We have explored possible
      interactions between the heads of heavy meromyosin (HMM) in the presence and
      absence of calcium and nucleotides by sedimentation and electron microscope
      studies. The ATPase activity of the HMM preparation was activated over tenfold by
      calcium, indicating that the preparation contained mostly regulated molecules. In
      the presence of ADP or ATP analogs, calcium increased the asymmetry of the HMM
      molecule as judged by its slower sedimentation velocity compared with that in
      EGTA. In the absence of nucleotide the asymmetry was high even in EGTA. The shift
      in sedimentation occurred with a sharp midpoint at a calcium level of about 0.5
      microM. Sedimentation of subfragment 1 was not dependent on calcium or on
      nucleotides. Modeling accounted for the observed sedimentation behavior by
      assuming that both HMM heads bent toward the tail in the absence of calcium,
      while in its presence the heads had random positions. The sedimentation pattern
      showed a single peak at all calcium concentrations, indicating equilibration
      between the two forms with a t(1/2) less than 70 seconds. Electron micrographs of
      crosslinked, rotary shadowed specimens indicated that 81 % of HMM molecules in
      the presence of nucleotide had both heads pointing back towards the tail in the
      absence of calcium, as compared with 41 % in its presence. This is consistent
      with the sedimentation data. We conclude that in the "off" state, scallop myosin
      heads interact with each other, forming a rigid structure with low ATPase
      activity. When molecules are switched "on" by binding of calcium, communication
      between the heads is lost, allowing them to flex randomly about the junction with
      the tail; this could facilitate their interaction with actin in contracting
      muscle.

PMID- 11243810
TI  - The importance of somatic mutations in the V(lambda) gene 2a2 in human monoclonal
      anti-DNA antibodies.
AB  - 2a2 is the most commonly rearranged gene in the human V(lambda )locus. It has
      been postulated that certain immunoglobulin genes (including 2a2) are rearranged
      preferentially because their germline sequences encode structures capable of
      binding to a range of antigens. Somatic mutation could then increase the
      specificity and affinity of binding to a particular antigen. We studied the
      properties of five IgG molecules in which the same heavy chain was paired with
      different light chains derived from 2a2. The pattern of somatic mutations in 2a2
      was shown to be crucial in conferring the ability to bind DNA, but two different
      patterns of mutation each conferred this ability.Computer-generated models of the
      three-dimensional structures of these antibodies illustrate the ability of 2a2 to
      form a DNA binding site in different ways. Somatic mutations at the periphery of
      the DNA binding site were particularly important. In two different light chains,
      mutations to arginine at different sites in the complementarity determining
      regions (CDRs) enhanced binding to DNA. In a third light chain, however, mutation
      to arginine at a different site blocked binding to DNA.

PMID- 11243811
TI  - Antibody inhibition of the transcriptase activity of the rotavirus DLP: a
      structural view.
AB  - On entering the host cell the rotavirus virion loses its outer shell to become a
      double-layered particle (DLP). The DLP then transcribes the 11 segments of its
      dsRNA genome using its own transcriptase complex, and the mature mRNA emerges
      along the 5-fold axis. In order to better understand the transcription mechanism
      and the role of VP6 in transcription we have studied three monoclonal antibodies
      against VP6: RV-238 which inhibits the transcriptase activity of the DLP; and RV
      133 and RV-138 which have no effect on transcription. The structures obtained by
      cryo-electron microscopy of the DLP/Fab complexes and by X-ray crystallography of
      the VP6 trimer and the VP6/Fab-238 complex have been combined to give pseudo
      atomic structures. Steric hindrance between the Fabs results in limited Fab
      occupancy. In particular, there are on average only three of a possible five Fabs
      238 which point towards the 5-fold axis. Thus, Fabs-238 are not in a position to
      block the exiting mRNA, nor is there any visible conformational change in VP6 on
      antibody binding at a resolution of 23 A. However, the epitope of the inhibiting
      antibody involves two VP6 monomers, whereas, those of the non-inhibiting
      antibodies have an epitope on only one VP6. Thus, the inhibition of transcription
      may be a result of inhibition of a possible change in the VP6 conformation
      associated with the transcription of mRNA.

PMID- 11243812
TI  - Papillomavirus capsid protein expression in Escherichia coli: purification and
      assembly of HPV11 and HPV16 L1.
AB  - The L1 major capsid proteins of human papillomavirus (HPV) types 11 and 16 were
      purified and analyzed for structural integrity and in vitro self-assembly.
      Proteins were expressed in Escherichia coli as glutathione-S-transferase-L1 (GST
      L1) fusions and purified to near homogeneity as pentamers (equivalent to viral
      capsomeres), after thrombin cleavage from the GST moiety and removal of tightly
      associated GroEL protein. Sequences at the amino and carboxy termini contributing
      to formation of L1 pentamers and to in vitro capsid assembly were identified by
      deletion analysis. For both HPV11 and HPV16 L1, up to at least ten residues could
      be deleted from the amino terminus (Delta N10) and 30 residues from the carboxy
      terminus (Delta C30) without affecting pentamer formation. The HPV16 pentamers
      assembled into relatively regular, 72-pentamer shells ("virus-like particles" or
      VLPs) at low pH, with the exception of HPV16 L1 Delta N10, which assembled into a
      12-pentamer, T=1 capsid (small VLP) under all conditions tested. The production
      of large quantities of assembly-competent L1, using the expression and
      purification protocol described here, has been useful for crystallographic
      analysis, and will be valuable for studies of virus-receptor interactions and
      potentially for vaccine design.

PMID- 11243814
TI  - Structure and function of the conserved 690 hairpin in Escherichia coli 16 S
      ribosomal RNA. II. NMR solution structure.
AB  - The solution structure of the conserved 690 hairpin from Escherichia coli 16 S
      rRNA was determined by NMR spectroscopy. The 690 loop is located at the surface
      of the 30 S subunit in the platform region and has been implicated in
      interactions with P-site bound tRNA, E-site mRNA, S11 binding, IF3 binding, and
      in RNA-RNA interactions with the 790 loop of 16 S rRNA and domain IV of 23 S
      rRNA. The structure reveals a novel sheared type G690.U697 base-pair with a
      single hydrogen bond from the G690 amino to U697-04. G691 and A696 also form a
      sheared pair and U692 forms a U-turn with an H-bond to the A695 non-bridging
      phosphate oxygen. The sheared pairs and U-turn result in the continuous single
      stranded stacking of five residues from 6693 to U697 with their Watson-Crick
      functional groups exposed in the minor groove. The overall fold of the 690
      hairpin is similar to the anticodon loop of tRNA. The structure provides an
      explanation for chemical protection patterns in the loop upon interaction with
      tRNA, the 50 S subunit, and S11. In vivo genetic studies demonstrate the
      functional importance of the motifs observed in the solution structure of the 690
      hairpin.

PMID- 11243813
TI  - Structural organization of the hepatitis B virus minichromosome.
AB  - The replicative intermediate of hepatitis B virus (HBV), the covalently closed,
      circular DNA, is organized into minichromosomes in the nucleus of the infected
      cell by histone and non-histone proteins. In this study we investigated the
      architecture of the HBV minichromosome in more detail. In contrast to cellular
      chromatin the nucleosomal spacing of the HBV minichromosome has been shown to be
      unusually reduced by approximately 10 %. A potential candidate responsible for an
      alteration in the chromatin structure of the HBV minichromosome is the HBV core
      protein. The HBV core protein has been implicated in the nuclear targeting
      process of the viral genome. The association of the HBV core protein with nuclear
      HBV replicative intermediates could strengthen this role. Our findings, confirmed
      by in vivo and in vitro experiments indicate that HBV core protein is a component
      of the HBV minichromosome, binds preferentially to HBV double-stranded DNA, and
      its binding results in a reduction of the nucleosomal spacing of the HBV
      nucleoprotein complexes by 10 %. From this model of the HBV minichromosome we
      propose that the HBV core protein may have an impact on the nuclear targeting of
      the HBV genome and be involved in viral transcription by regulating the
      nucleosomal arrangement of the HBV regulatory elements, probably in a positive
      manner.

PMID- 11243815
TI  - Structure and function of the conserved 690 hairpin in Escherichia coli 16 S
      ribosomal RNA. III. Functional analysis of the 690 loop.
AB  - An instant-evolution experiment was performed on the eight nucleotides comprising
      the loop region of the 690 hairpin in Escherichia coli 16 S ribosomal RNA.
      Positions 690 to 697 were randomly mutated and 101 unique functional mutants were
      isolated, sequenced and analyzed for function in vivo. Non-random nucleotide
      distributions were observed at each of the mutated positions except 693 and 694.
      Nucleotide identity significantly affected ribosome function at positions 690,
      695, 696 and 697. Pyrimidines were absent at position 696 in the instant
      evolution pool as were C at position 691 and G at position 697. A highly
      significant covariation was observed between nucleotides 690 and 697. No
      functional double mutants at positions 691 and 696 were obtained from the instant
      evolution pool. In our NMR structure of the 690 loop, both the G690.U697 and
      G691.A696 form sheared hydrogen-bonded mismatches. To further examine the
      functional constraints between these paired nucleotides, one set of site-directed
      mutations was constructed at positions 690:697 and another set was constructed at
      positions 691:696. Functional analysis of the site-directed mutants is consistent
      with our instant-evolution findings and revealed constraints on the placement of
      specific functional groups observed in the NMR structure. Ten instant-evolution
      mutants were isolated that are more functional than the wild-type. Hyperactivity
      in these mutants correlates with a single mutation at position 693.

PMID- 11243816
TI  - Structural and energetic analysis of RNA recognition by a universally conserved
      protein from the signal recognition particle.
AB  - The signal recognition particle (SRP) is a ribonucleoprotein complex responsible
      for targeting proteins to the endoplasmic reticulum in eukarya or to the inner
      membrane in prokarya. The crystal structure of the universally conserved RNA
      protein core of the Escherichia coli SRP, refined here to 1.5 A resolution,
      revealed minor groove recognition of the 4.5 S RNA component by the M domain of
      the Ffh protein. Within the RNA, nucleotides comprising two phylogenetically
      conserved internal loops create a unique surface for protein recognition. To
      determine the energetic importance of conserved nucleotides for SRP assembly, we
      measured the affinity of the M domain for a series of RNA mutants. This analysis
      reveals how conserved nucleotides within the two internal loop motifs establish
      the architecture of the macromolecular interface and position essential
      functional groups for direct recognition by the protein.

PMID- 11243817
TI  - Crystal structure of unligated guanylate kinase from yeast reveals GMP-induced
      conformational changes.
AB  - The crystal structure of guanylate kinase (GK) from yeast (Saccharomyces
      cerevisiae) with a non-acetylated N terminus has been determined in its unligated
      form (apo-GK) as well as in complex with GMP (GK.GMP). The structure of apo-GK
      was solved with multiwavelength anomalous diffraction data and refined to an R
      factor of 0.164 (R(free)=0.199) at 2.3 A resolution. The structure of GK.GMP was
      determined using the crystal structure of GK with an acetylated N terminus as the
      search model and refined to an R-factor of 0.156 (R(free)=0.245) at 1.9 A. GK
      belongs to the family of nucleoside monophosphate (NMP) kinases and catalyzes the
      reversible phosphoryl transfer from ATP to GMP. Like other NMP kinases, GK
      consists of three dynamic domains: the CORE, LID, and NMP-binding domains.
      Dramatic movements of the GMP-binding domain and smaller but significant
      movements of the LID domain have been revealed by comparing the structures of apo
      GK and GK.GMP. apo-GK has a much more open conformation than the GK.GMP complex.
      Systematic analysis of the domain movements using the program DynDom shows that
      the large movements of the GMP-binding domain involve a rotation around an
      effective hinge axis approximately parallel with helix 3, which connects the GMP
      binding and CORE domains. The C-terminal portion of helix 3, which connects to
      the CORE domain, has strikingly higher temperature factors in GK.GMP than in apo
      GK, indicating that these residues become more mobile upon GMP binding. The
      results suggest that helix 3 plays an important role in domain movement. Unlike
      the GMP-binding domain, which moves toward the active center of the enzyme upon
      GMP binding, the LID domain moves away from the active center and makes the
      presumed ATP-binding site more open. Therefore, the LID domain movement may
      facilitate the binding of MgATP. The structure of the recombinant GK.GMP complex
      superimposes very well with that of the native GK.GMP complex, indicating that N
      terminal acetylation does not have significant impact on the three-dimensional
      structure of GK.

PMID- 11243818
TI  - The functional similarity and structural diversity of human and cartilaginous
      fish hemoglobins.
AB  - Although many descriptions of adaptive molecular evolution of vertebrate
      hemoglobins (Hb) can be found in physiological text books, they are based mainly
      on changes of the primary structure and place more emphasis on conservation than
      alterations at the functional site. Sequence analysis alone, however, does not
      reveal much about the evolution of new functions in proteins. It was found
      recently that there are many functionally important structural differences
      between human and a ray (Dasyatis akajei) Hb even where sequence is conserved
      between the two. We have solved the structures of the deoxy and CO forms of a
      second cartilaginous fish (a shark, Mustelus griseus) Hb, and compared it with
      structures of human Hb, two bony fish Hbs and the ray Hb in order to understand
      more about how vertebrate Hbs have functionally evolved by the selection of
      random amino acid substitutions. The sequence identity of cartilaginous fish Hb
      and human Hb is a little less than 40 %, with many functionally important amino
      acid replacements. Wider substitutions than usually considered as neutral have
      been accepted in the course of molecular evolution of Hb. As with the ray Hb, the
      shark Hb shows functionally important structural differences from human Hb that
      involve amino acid substitutions and shifts of preserved amino acid residues
      induced by substitutions in other parts of the molecule. Most importantly, beta
      E11Val in deoxy human Hb, which overlaps the ligand binding site and is
      considered to play a key role in controlling the oxygen affinity, moves away
      about 1 A in both the shark and ray Hbs. Thus adaptive molecular evolution is
      feasible as a result of both functionally significant mutations and deviations of
      preserved amino acid residues induced by other amino acid substitutions.

PMID- 11243819
TI  - An unexpected extended conformation for the third TPR motif of the peroxin PEX5
      from Trypanosoma brucei.
AB  - A number of helix-rich protein motifs are involved in a variety of critical
      protein-protein interactions in living cells. One of these is the tetratrico
      peptide repeat (TPR) motif that is involved, amongst others, in cell cycle
      regulation, chaperone function and post-translation modifications. So far, these
      helix-rich TPR motifs have always been observed to be a compact unit of two
      helices interacting with each other in antiparallel fashion. Here, we describe
      the structure of the first three TPR-motifs of the peroxin PEX5 from Trypanosoma
      brucei, the causative agent of sleeping sickness. Peroxins are proteins involved
      in peroxisome, glycosome and glyoxysome biogenesis. PEX5 is the receptor of the
      proteins targeted to these organelles by the "peroxisomal targeting signal-1", a
      C-terminal tripeptide called PTS-1. The first two of the three TPR-motifs of T.
      brucei PEX5 appear to adopt the canonical antiparallel helix hairpin structure.
      In contrast, the third TPR motif of PEX5 has a dramatically different
      conformation in our crystals: the two helices that were supposed to form a
      hairpin are folded into one single 44 A long continuous helix. Such a
      conformation has never been observed before for a TPR motif. This raises
      interesting questions including the potential functional importance of a "jack
      knife" conformational change in TPR motifs.

PMID- 11243820
TI  - The crystal structure of dTDP-D-Glucose 4,6-dehydratase (RmlB) from Salmonella
      enterica serovar Typhimurium, the second enzyme in the dTDP-l-rhamnose pathway.
AB  - l-Rhamnose is a 6-deoxyhexose that is found in a variety of different
      glycoconjugates in the cell walls of pathogenic bacteria. The precursor of l
      rhamnose is dTDP-l-rhamnose, which is synthesised from glucose- 1-phosphate and
      deoxythymidine triphosphate (dTTP) via a pathway requiring four enzymes.
      Significantly this pathway does not exist in humans and all four enzymes
      therefore represent potential therapeutic targets. dTDP-D-glucose 4,6-dehydratase
      (RmlB; EC 4.2.1.46) is the second enzyme in the dTDP-L-rhamnose biosynthetic
      pathway. The structure of Salmonella enterica serovar Typhimurium RmlB had been
      determined to 2.47 A resolution with its cofactor NAD(+) bound. The structure has
      been refined to a crystallographic R-factor of 20.4 % and an R-free value of 24.9
      % with good stereochemistry.RmlB functions as a homodimer with monomer
      association occurring principally through hydrophobic interactions via a four
      helix bundle. Each monomer exhibits an alpha/beta structure that can be divided
      into two domains. The larger N-terminal domain binds the nucleotide cofactor
      NAD(+) and consists of a seven-stranded beta-sheet surrounded by alpha-helices.
      The smaller C-terminal domain is responsible for binding the sugar substrate dTDP
      d-glucose and contains four beta-strands and six alpha-helices. The two domains
      meet to form a cavity in the enzyme. The highly conserved active site
      Tyr(167)XXXLys(171) catalytic couple and the GlyXGlyXXGly motif at the N terminus
      characterise RmlB as a member of the short-chain dehydrogenase/reductase extended
      family. The quaternary structure of RmlB and its similarity to a number of other
      closely related short-chain dehydrogenase/reductase enzymes have enabled us to
      propose a mechanism of catalysis for this important enzyme.

PMID- 11243821
TI  - Crystal structure of the Acidaminococcus fermentans 2-hydroxyglutaryl-CoA
      dehydratase component A.
AB  - Acidaminococcus fermentans degrades glutamate via the hydroxyglutarate pathway,
      which involves the syn-elimination of water from (R)-2-hydroxyglutaryl-CoA in a
      key reaction of the pathway. This anaerobic process is catalyzed by 2
      hydroxyglutaryl-CoA dehydratase, an enzyme with two components (A and D) that
      reversibly associate during reaction cycles. Component A (CompA), a homodimeric
      protein of 2x27 kDa, contains a single, bridging [4Fe-4S] cluster and uses the
      hydrolysis of ATP to deliver an electron to the dehydratase component (CompD),
      where the electron is used catalytically. The structure of the extremely oxygen
      sensitive CompA protein was solved by X-ray crystallography to 3 A resolution.
      The protein was found to be a member of the actin fold family, revealing a
      similar architecture and nucleotide-binding site. The key differences between
      CompA and other members of the actin fold family are: (i) the presence of a
      cluster binding segment, the "cluster helix"; (ii) the [4Fe-4S] cluster; and
      (iii) the location of the homodimer interface, which involves the bridging
      cluster. Possible reaction mechanisms are discussed in light of the close
      structural similarity to members of the actin-fold family and the functional
      similarity to the nitrogenase Fe- protein.

PMID- 11243822
TI  - Self-association reaction of denatured staphylococcal nuclease fragments
      characterized by heteronuclear NMR.
AB  - The self-association reaction of denatured staphylococcal nuclease fragments,
      urea-denatured G88W110, containing residues 1-110 and mutation G88W, and
      physiologically denatured 131-residue Delta 131 Delta, have been characterized by
      NMR at close to neutral pH. The two fragments differ in the extent and degree of
      association due to the different sequence and experimental conditions. Residues
      13-39, which show significant exchange line broadening, constitute the main
      association interface in both fragments. A second weak association region was
      identified involving residues 79-105 only in the case of urea-denatured G88W110.
      For residues involved in the association reaction, significant suppression of the
      line broadening and small but systematic chemical shift variation of the amide
      protons were observed as the protein concentration decreased. The direction of
      chemical shift change suggests that the associated state adopts mainly beta-sheet
      like conformation, and the beta-hairpin formed by strands beta 2 and beta 3 is
      native-like. The apparent molecular size obtained by diffusion coefficient
      measurements shows a weak degree of association for Delta 131 Delta below 0.4 mM
      protein concentration and for G88W110 in 4 M urea. In both cases the fragments
      are predominantly in the monomeric state. However, the weak association reaction
      can significantly influence the transverse relaxation of residues involved in the
      association reaction. The degree of association abruptly increases for Delta 131
      Delta above 0.4 mM concentration, and it is estimated to form a 4 to 8 mer at 2
      mM. It is proposed that the main region involved in association forms the core
      structure, with the remainder of residues largely disordered in the associated
      state. Despite the obvious influence of the association reaction on the slow
      motion of the backbone, the restricted mobility on the nanosecond timescale
      around the region of strand beta 5 is essentially unaffected by the association
      reaction and degree of denaturation.

PMID- 11243823
TI  - Solution structure and dynamics of the central CCP module pair of a poxvirus
      complement control protein.
AB  - The complement control protein (CCP) module (also known as SCR, CCP or sushi
      domain) is prevalent amongst proteins that regulate complement activation.
      Functional and mutagenesis studies have shown that in most cases two or more
      neighbouring CCP modules form specific binding sites for other molecules. Hence
      the orientation in space of a CCP module with respect to its neighbours and the
      flexibility of the intermodular junction are likely to be critical for function.
      Vaccinia virus complement control protein (VCP) is a complement regulatory
      protein composed of four tandemly arranged CCP modules. The solution structure of
      the carboxy-terminal half of this protein (CCP modules 3 and 4) has been solved
      previously. The structure of the central portion (modules 2 and 3, VCP
      approximately 2,3) has now also been solved using NMR spectroscopy at 37 degrees
      C. In addition, the backbone dynamics of VCP approximately 2,3 have been
      characterised by analysis of its (15)N relaxation parameters. Module 2 has a
      typical CCP module structure while module 3 in the context of VCP approximately
      2,3 has some modest but significant differences in structure and dynamics to
      module 3 within the 3,4 pair. Modules 2 and 3 do not share an extensive
      interface, unlike modules 3 and 4. Only two possible NOEs were identified between
      the bodies of the modules, but a total of 40 NOEs between the short intermodular
      linker of VCP approximately 2,3 and the bodies of the two modules determines a
      preferred, elongated, orientation of the two modules in the calculated
      structures. The anisotropy of rotational diffusion has been characterised from
      (15)N relaxation data, and this indicates that the time-averaged structure is
      more compact than suggested by (1)H-(1)H NOEs. The data are consistent with the
      presence of many intermodular orientations, some of which are kinked, undergoing
      interconversion on a 10(-8)-10(-6) second time-scale. A reconstructed
      representation of modules 2-4 allows visualisation of the spatial arrangement of
      the 11 substitutions that occur in the more potent complement inhibitor from
      Variola (small pox) virus.

PMID- 11243824
TI  - Refined structures of beta-ketoacyl-acyl carrier protein synthase III.
AB  - beta-Ketoacyl-acyl carrier protein synthase III (FabH) is a condensing enzyme
      that plays central roles in fatty acid biosynthesis. Three-dimensional structures
      of E. coli FabH in the presence and absence of ligands have been refined to 1.46
      A resolution. The structures of improved accuracy revealed detailed interactions
      involved in ligand binding. These structures also provided new insights into the
      FabH mechanism, e.g. the possible role of a water or hydroxyl anion in Cys112
      deprotonation. A structure of the apo enzyme uncovered large conformational
      changes in the active site, exemplified by the disordering of four essential
      loops (84-86, 146-152, 185-217 and 305-307) and the movement of catalytic
      residues (Cys112 and His244). The disordering of the loops leads to greater than
      50 % reduction in the FabH dimer interface, suggesting a dynamic nature for an
      unusually large portion of the dimer interface. The existence of a large solvent
      accessible channel in the dimer interface as well as two cis-peptides (cis-Pro88
      and cis-Phe308) in two of the disordered loops may explain the observed
      structural instabilities.

PMID- 11243825
TI  - C-H...pi-interactions in proteins.
AB  - A non-redundant set of 1154 protein structures from the Protein Data Bank was
      examined with respect to close interactions between C-H-donor and pi-acceptor
      groups. A total of 31,087 interactions were found to satisfy our selection
      criteria. Their geometric parameters suggest that these interactions can be
      classified as weak hydrogen bonds.A set of 12 interaction classes were defined
      based on the division of the donors into three groups and the acceptors into four
      groups. These classes were examined separately, and the respective interactions
      described in detail in each class. Most prominent were interactions between
      aliphatic C-H donors and aromatic pi-acceptors and interactions between aromatic
      C-H donors and aromatic pi-acceptors. About three-quarters of the Trp-rings, half
      of all Phe and Tyr-rings and a quarter of all His-rings were found to be involved
      as acceptors in C-H...pi-interactions. On the donor side, a preference for
      aromatic C-H groups was observed, but also for the aliphatic side-chains of the
      long, extended amino acid residues Lys, Arg and Met, and the Pro ring. The
      average distance between the C-donor and the center-of-mass of the pi-acceptor
      was observed to be significantly longer in the 174 protein structures determined
      at >2.5 A resolution. Also, the distribution is significantly wider. This
      resolution dependence suggests that the force fields commonly used for the
      refinement of protein structures may not be adequate. C-H...pi-interactions
      involving aromatic groups either as donor or as acceptor groups are found mostly
      in the interior of the protein. The more hydrophilic the participating groups
      are, the closer to the surface are the interactions located. About 40 % of all C
      H...pi-interactions occur between amino acid residue side-chains that are
      separated by nine or less residues in sequence. Dependent on the interaction
      class, different preferences for secondary structure, residue type and side-chain
      conformation were observed. It is likely that the C-H...pi-interactions
      contribute significantly to the overall stability of a protein.

PMID- 11243826
TI  - Detection of two partially structured species in the folding process of the
      amyloidogenic protein beta 2-microglobulin.
AB  - beta 2-Microglobulin is a small, major histocompatibility complex class I
      associated protein that undergoes aggregation and accumulates as amyloid deposits
      in human tissues as a consequence of long-term haemodialysis. The folding process
      of this amyloidogenic protein has been studied in vitro by diluting the guanidine
      hydrochloride-denatured protein in refolding buffer at pH 7.4 and monitoring the
      folding process by means of a number of spectroscopic probes that allow the
      native structure of the protein to be detected as it develops. These techniques
      include fluorescence spectroscopy, far and near-UV circular dichroism, 8-anilino
      1-naphthalenesulfonic acid binding and double jump assays. All spectroscopic
      probes indicate that a significant amount of structure forms within the dead-time
      of stopped-flow measurements (<5 ms). The folding reaction goes to completion
      through a fast phase followed by a slow phase, whose rate constants are ca 5.1
      and 0.0030 s(-1) in water, respectively. Unfolding-folding double jump
      experiments, together with the use of peptidyl prolyl isomerase, reveal that the
      slow phase of folding of beta 2-microglobulin is not fundamentally determined by
      cis/trans isomerisation of X-Pro peptide bonds. Other folding-unfolding double
      jump experiments also suggest that the fast and slow phases of folding are not
      related to independent folding of different populations of protein molecules.
      Rather, we provide evidence for a sequential mechanism of folding where denatured
      beta 2-microglobulin collapses to an ensemble of partially folded conformations
      (I(1)) which fold subsequently to a more highly structured species (I(2)) and,
      finally, attain the native state. The partially folded species I(2) appears to be
      closely similar to previously studied amyloidogenic forms of beta 2
      microglobulin, such as those adopted by the protein at mildly acid pH values and
      by a variant with six residues deleted at the N terminus. Since amyloid formation
      in vivo originates from partial denaturation of beta 2-microglobulin under
      conditions favouring the folding process, the long-lived, partially structured
      species detected here might be significantly populated under some physiological
      conditions and hence might play an important role in the process of amyloid
      formation.

PMID- 11243827
TI  - Using chimeric immunity proteins to explore the energy landscape for alpha
      helical protein folding.
AB  - To address the role of sequence in the folding of homologous proteins, the
      folding and unfolding kinetics of the all-helical bacterial immunity proteins Im2
      and Im9 were characterised, together with six chimeric derivatives of these
      proteins. We show that both Im2 and Im9 fold rapidly (k(UN)(H(2)O)) approximately
      2000 s(-1) at pH 7.0, 25 degrees C) in apparent two-state transitions, through
      rate-limiting transition states that are highly compact (beta(TS)0.93 and 0.96,
      respectively). Whilst the folding and unfolding properties of three of the
      chimeras (Im2 (1-44)(Im9), Im2 (1-64)(Im9 )and Im2 (25-44)(Im9)) are similar to
      their parental counterparts, in other chimeric proteins the introduced sequence
      variation results in altered kinetic behaviour. At low urea concentrations, Im2
      (1-29)(Im9) and Im2 (56-64)(Im9) fold in two-state transitions via transition
      states that are significantly less compact (beta(TS) approximately 0.7) than
      those characterised for the other immunity proteins presented here. At higher
      urea concentrations, however, the rate-limiting transition state for these two
      chimeras switches or moves to a more compact species (beta(TS) approximately
      0.9). Surprisingly, Im2 (30-64)(Im9) populates a highly collapsed species
      (beta(I)=0.87) in the dead-time (2.5 ms) of stopped flow measurements. These data
      indicate that whilst topology may place significant constraints on the folding
      process, specific inter-residue interactions, revealed here through multiple
      sequence changes, can modulate the ruggedness of the folding energy landscape.

PMID- 11243828
TI  - Docking ligands onto binding site representations derived from proteins built by
      homology modelling.
AB  - Due to the abundant sequence information available from genome projects, an
      increasing number of structurally unknown proteins, homologous to examples of
      known 3D structure, will be discovered as new targets for drug design. Since
      homology models do not provide sufficient accuracy to apply common drug design
      tools, a new approach, DragHome, has been developed to dock ligands into such
      approximate protein models. DragHome combines information from homology modelling
      with ligand data, used by and derived from 3D quantitative structure-activity
      relationships (QSAR). The binding-site of a model-built protein is analysed in
      terms of putative ligand interaction sites and translated via Gaussian functions
      into a functional binding-site description represented by physico-chemical
      properties. Ligands to be docked onto these binding-site representations are
      similarly translated into a description based on Gaussian functions. The docking
      is computed by optimising the overlap between the functional description of the
      binding site and the ligand, generating multiple solutions. For a set of
      different ligands, these solutions are ranked according to the internal
      similarity consistance among the various ligands in the binding modes obtained
      from docking. DragHome has been validated at examples for which crystal
      structures are available: structurally distinct thrombin inhibitors were docked
      onto models of thrombin generated from serine proteases of 28 to 40 % sequence
      identity, yielding ligand binding modes with an average RMS deviation of 1.4 A.
      Mostly the near-native solutions are ranked best. Molecular flexibility of
      ligands can be considered in terms of pre-calculated multiple conformers.
      DragHome has been used to automatically generate an alignment of 88 thrombin
      inhibitors, for which a significant 3D QSAR model could be derived. The
      contribution maps resulting from this analysis can be interpreted with respect to
      the surrounding protein model. They highlight inconsistencies and deficiencies
      present in the model. In future developments, this information could be fed back
      into a subsequent modelling step to improve the protein model.

PMID- 11243829
TI  - Generalized dead-end elimination algorithms make large-scale protein side-chain
      structure prediction tractable: implications for protein design and structural
      genomics.
AB  - The dead-end elimination (DEE) theorems are powerful tools for the combinatorial
      optimization of protein side-chain placement in protein design and homology
      modeling. In order to reach their full potential, the theorems must be extended
      to handle very hard problems. We present a suite of new algorithms within the DEE
      paradigm that significantly extend its range of convergence and reduce run time.
      As a demonstration, we show that a total protein design problem of 10(115)
      combinations, a hydrophobic core design problem of 10(244) combinations, and a
      side-chain placement problem of 10(1044) combinations are solved in less than two
      weeks, a day and a half, and an hour of CPU time, respectively. This extends the
      range of the method by approximately 53, 144 and 851 log-units, respectively,
      using modest computational resources. Small to average-sized protein domains can
      now be designed automatically, and side-chain placement calculations can be
      solved for nearly all sizes of proteins and protein complexes in the growing
      field of structural genomics.

PMID- 11243830
TI  - ConSurf: an algorithmic tool for the identification of functional regions in
      proteins by surface mapping of phylogenetic information.
AB  - Experimental approaches for the identification of functionally important regions
      on the surface of a protein involve mutagenesis, in which exposed residues are
      replaced one after another while the change in binding to other proteins or
      changes in activity are recorded. However, practical considerations limit the use
      of these methods to small-scale studies, precluding a full mapping of all the
      functionally important residues on the surface of a protein. We present here an
      alternative approach involving the use of evolutionary data in the form of
      multiple-sequence alignment for a protein family to identify hot spots and
      surface patches that are likely to be in contact with other proteins, domains,
      peptides, DNA, RNA or ligands. The underlying assumption in this approach is that
      key residues that are important for binding should be conserved throughout
      evolution, just like residues that are crucial for maintaining the protein fold,
      i.e. buried residues. A main limitation in the implementation of this approach is
      that the sequence space of a protein family may be unevenly sampled, e.g. mammals
      may be overly represented. Thus, a seemingly conserved position in the alignment
      may reflect a taxonomically uneven sampling, rather than being indicative of
      structural or functional importance. To avoid this problem, we present here a
      novel methodology based on evolutionary relations among proteins as revealed by
      inferred phylogenetic trees, and demonstrate its capabilities for mapping binding
      sites in SH2 and PTB signaling domains. A computer program that implements these
      ideas is available freely at: http://ashtoret.tau.ac.il/ approximately rony

PMID- 11243831
TI  - Acetohydroxyacid synthase: a proposed structure for regulatory subunits supported
      by evidence from mutagenesis.
AB  - Valine inhibition of acetohydroxyacid synthase (AHAS) plays an important role in
      regulation of biosynthesis of branched-chain amino acids in bacteria. Bacterial
      AHASs are composed of separate catalytic and regulatory subunits; while the
      catalytic subunits appear to be homologous with several other thiamin diphosphate
      dependent enzymes, there has been no model for the structure of the small,
      regulatory subunits (SSUs). AHAS III is one of three isozymes in Escherichia
      coli. Its large subunit (encoded by ilvI) by itself has 3-5 % activity of the
      holoenzyme and is not sensitive to inhibition by valine. The SSU (encoded by
      ilvH) associates with the large subunit and is required for full catalytic
      activity and valine sensitivity. The isolated SSU binds valine. The properties of
      several mutant SSUs shed light on the relation between their structure and
      regulatory function. Three mutant SSUs were obtained from spontaneous Val(R)
      bacterial mutants and three more were designed on the basis of an alignment of
      SSU sequences from valine-sensitive and resistant isozymes, or consideration of
      the molecular model developed here. Mutant SSUs N11A, G14D, N29H and A36V, when
      reconstituted with wild-type large subunit, lead to a holoenzyme with drastically
      reduced valine sensitivity, but with a specific activity similar to that of the
      wild-type. The isolated G14D and N29H subunits do not bind valine. Mutant Q59L
      leads to a valine-sensitive holoenzyme and isolated Q59L binds valine. T34I has
      an intermediate valine sensitivity. The effects of mutations on the affinity of
      the large subunits for SSUs also vary. D. Fischer's hybrid fold prediction method
      suggested a fold similarity between the N terminus of the ilvH product and the C
      terminal regulatory domain of 3-phosphoglycerate dehydrogenase. On the basis of
      this prediction, together with the properties of the mutants, a model for the
      structure of the AHAS SSUs and the location of the valine-binding sites can be
      proposed.

PMID- 11243833
TI  - A simple and efficient method to transcribe RNAs with reduced 3' heterogeneity.
AB  - Ribose C2' methoxy groups (-OCH3) on the penultimate nucleotide or the last two
      nucleotides of DNA templates can dramatically improve the quality of transcripts
      produced by T7 RNA polymerase. This strategy can be adapted to generate
      transcripts of varying lengths and will allow greater ease in purification of the
      products.

PMID- 11243834
TI  - RNA oligonucleotide synthesis via 5'-silyl-2'-orthoester chemistry.
AB  - The chemical synthesis of RNA oligonucleotides is a valuable resource for
      biological research. A new approach for RNA synthesis that is now as reliable and
      efficient as DNA synthesis methods is described in this report. A 5'-O-silyl
      ether is used in conjunction with acid-labile orthoester protecting groups on the
      2'-hydroxyls. RNA synthesis proceeds efficiently on commercial synthesizers in
      high yields. Analysis by anion-exchange HPLC shows that the quality and yields of
      RNA synthesized with this chemistry are unprecedented. Furthermore, this
      chemistry enables analysis and purification of stable 2'-O-protected RNA. This
      property serves to minimize possibilities for degradation of the RNA. In
      addition, it now possible to analyze troublesome sequences, which, when fully 2'
      O-deprotected, do not easily resolve into one major conformation due to strong
      secondary structure. When ready for use, the RNA is easily 2'-O-deprotected in
      mild-acidic aqueous buffers in 30 min. This new RNA chemistry has enabled the
      routine high-quality synthesis of RNA oligonucleotides up to 50 bases in length
      regardless of sequence or secondary structure.

PMID- 11243835
TI  - Phenanthroline-Cu(II) cleavage as a probe of rRNA structure.
AB  - Chemical cleavage is developing into a powerful tool for analysis and
      characterization of nucleic acids. Phenanthroline-Cu(II) cleavage has been used
      extensively for studies of DNA for the last two decades, but recently has been
      applied to structural studies of RNA as well. This approach has been used to
      study the structure and structural changes occurring in ribosomal RNA within the
      ribosomes. In this article we discuss the mechanism by which phenanthroline
      cleaves, the applications possible using this approach, and the results that can
      be obtained. Protocols for use of phenanthroline are outlined as well.

PMID- 11243836
TI  - Time-resolved hydroxyl-radical footprinting of RNA using Fe(II)-EDTA.
AB  - Chemical footprinting methods have been used extensively to probe the structures
      of biologically important RNAs at nucleotide resolution. One of these methods,
      hydroxyl-radical footprinting, has recently been employed to study the kinetics
      of RNA folding. Hydroxyl radicals can be generated by a number of different
      methods, including Fe(II)-EDTA complexes, synchrotron radiation, and
      peroxynitrous acid disproportionation. The latter two methods have been used for
      kinetic studies of RNA folding. We have taken advantage of rapid hydroxyl-radical
      generation by Fe(II)-EDTA-hydrogen peroxide solutions to develop a benchtop
      method to study folding kinetics of RNA complexes. This technique can be
      performed using commercially available chemicals, and can be used to accurately
      define RNA folding rate constants slower than 6 min(-1). Here we report the
      method and an example of time-resolved footprinting on the hairpin ribozyme, a
      small endoribonuclease and RNA ligase.

PMID- 11243837
TI  - RNA conformation and folding studied with fluorescence resonance energy transfer.
AB  - Fluorescence resonance energy transfer (FRET) results from nonradiative coupling
      of two fluorophores and reports on distances in the range 10-100 A. It is
      therefore a suitable probe to determine distances in RNA molecules and define
      their global structure, to follow kinetics of RNA conformational changes during
      folding in real time, to monitor ion binding, or to analyze conformational
      equilibria and assess the thermodynamic stability of tertiary structure
      conformers. Along with the basic principles of steady-state and time-resolved
      fluorescence resonance energy transfer measurements, approaches to investigate
      RNA conformational transitions and folding are described and illustrated with
      selected examples. The versatility of FRET-based techniques has recently been
      demonstrated by implementations of FRET in high-throughput screening of potential
      drugs as well as studies of energy transfer that monitor RNA conformational
      changes on the single-molecule level.

PMID- 11243838
TI  - Using nucleotide analogs to probe protein-RNA interactions.
AB  - Synthetic nucleotide analogs provide the opportunity to evaluate the importance
      of individual functional groups on the RNA in protein-RNA complexes. The general
      approach is to incorporate analogs at a defined position(s) in the RNA target and
      to evaluate the effect of this substitution on the thermodynamic stability of the
      protein-RNA complex. The underlying assumption is that if the presence of the
      analog reduces the stability of the complex, then the functional groups that are
      altered in the analog interact with the protein. Here we describe the protocols
      for incorporation of nucleotide analogs either by in vitro transcription using T7
      RNA polymerase or by synthetic chemistry. We also describe how we have used this
      approach to study the interaction of the TRAP protein from Bacillus subtilis with
      its cognate RNAs consisting of 11 repeats of GAG and/or UAG triplets. By
      comparing the results of these analog studies with the crystal structure of TRAP
      bound to an RNA containing 11 GAG repeats, we are able to see that all the
      functional groups identified by analogs forge direct interactions with the
      protein. Analog studies also correctly identified residues that do not contact
      the protein. Moreover, analogs can have indirect effects on the complex stability
      by altering the structural properties of the RNA.

PMID- 11243839
TI  - Biochemical detection of monovalent metal ion binding sites within RNA.
AB  - Many RNAs, including the ribosome, RNase P, and the group II intron, explicitly
      require monovalent cations for activity in vitro. Although the necessity of
      monovalent cations for RNA function has been known for more than a quarter of a
      century, the characterization of specific monovalent metal sites within large
      RNAs has been elusive. Here we describe a biochemical approach to identify
      functionally important monovalent cations in nucleic acids. This method uses
      thallium (Tl+), a soft Lewis acid heavy metal cation with chemical properties
      similar to those of the physiological alkaline earth metal potassium (K+).
      Nucleotide analog interference mapping (NAIM) with the sulfur-substituted
      nucleotide 6-thioguanosine in combination with selective metal rescue of the
      interference with Tl+ provides a distinct biochemical signature for monovalent
      metal ion binding. This approach has identified a K+ binding site within the P4
      P6 domain of the Tetrahymena group I intron that is also present within the X-ray
      crystal structure. The technique also predicted a similar binding site within the
      Azoarcus group I intron where the structure is not known. The approach is
      applicable to any RNA molecule that can be transcribed in vitro and whose
      function can be assayed.

PMID- 11243840
TI  - Probing RNA in vivo with methylation guide small nucleolar RNAs.
AB  - Most box C/D small nucleolar RNAs (snoRNAs) direct the formation of 2'-O
      methylated nucleotides in ribosomal RNA and, apparently, other RNAs present in
      the nucleolar complex. Sites to be modified are selected by a long (>10-nt)
      antisense guide sequence in the snoRNA and a distance measurement from a box D or
      D' element that follows the snoRNA guide sequence. Modification of the substrate
      occurs in the region of complementarity, at a position five nucleotides upstream
      from box D/D'. Methylation can be targeted to novel sites by expressing a snoRNA
      with a new guide sequence. In some cases methylation impairs the growth rate of
      the cell, indicating that a functionally important nucleotide has been altered.
      With a view to harnessing snoRNA-directed methylation for functional mapping, we
      have developed a method for constructing libraries of snoRNA genes that, in
      principle, can introduce methylation point mutations into any rRNA segment of
      interest. The strategy and procedures are described here, and preliminary results
      are presented that show the feasibility of using this technology to probe a
      region of the yeast large subunit rRNA that includes the core of the
      peptidyltransferase center.

PMID- 11243841
TI  - Selection of RNA-binding peptides using mRNA-peptide fusions.
AB  - We have been working to apply in vitro selection to isolate novel RNA-binding
      peptides. To do this, we use mRNA-protein fusions, peptides covalently attached
      to their own mRNA. Here, we report selection protocols developed using the
      arginine-rich domain of bacteriophage lambda-N protein and its binding target,
      the boxB RNA. Systematic investigation of possible paths for a selection round
      has allowed us to design a reliable and efficient protocol to enrich RNA-binding
      peptides from nonfunctional members of a complex mixture. The protocols we have
      developed should greatly facilitate the isolation of new molecules using the
      fusion system.

PMID- 11243842
TI  - Hrs and hbp: possible regulators of endocytosis and exocytosis.
AB  - The molecular mechanisms of endocytosis and exocytosis are not yet fully
      understood. Hrs and Hbp, two tightly associated proteins in eukaryotic cells,
      have been implicated in these cellular processes. Hrs is homologous to Vps27p, an
      endosomal protein required for vacuolar and endocytic trafficking in yeast. Hrs
      is localized to early endosomes and is required for the normal morphology of
      early endosomes in mammalian cells. Hrs also associates with proteins implicated
      in endocytosis and exocytosis such as SNAP-25 and Eps15. Hrs treatment inhibits
      neurotransmitter release in permeabilized neuronal cells and its overexpression
      inhibits internalization of transferrin. Overexpression of dominant-negative Hbp
      mutants inhibits ligand-induced downregulation of growth factor/receptor
      complexes and immunoglobulin E receptor-triggered degranulation of secretory
      granules in mast cells. These observations suggest an important role for the
      Hrs/Hbp protein complex in vesicular trafficking during endocytosis and
      exocytosis.

PMID- 11243843
TI  - Imidazoline RX871024 raises diacylglycerol levels in rat pancreatic islets.
AB  - Imidazoline compound RX871024 and carbamylcholine (CCh) stimulate insulin
      secretion in isolated rat pancreatic islets. Combination of CCh and RX871024
      induces a synergetic effect on insulin secretion. RX871024 and CCh produce
      twofold increases in diacylglycerol (DAG) concentration. The combination of two
      compounds has an additive effect on DAG concentration. Effects of RX871024 on
      insulin secretion and DAG concentration are not dependent on the presence of
      D609, an inhibitor of phosphatidylcholine-specific phospholipase C. It is
      concluded that as in case with CCh the increase in DAG concentration induced by
      imidazoline RX871024 contributes to the insulinotropic activity of the compound.

PMID- 11243844
TI  - Tissue factor is not involved in the mitogenic activity of factor VIIa.
AB  - The present study was undertaken to evaluate in vitro the importance of tissue
      factor in the mitogenic effect of factor VIIa for embryonic fibroblasts. For that
      purpose, embryonic fibroblasts were isolated from either wild-type or transgenic
      mice showing a single inactivation of the tissue factor gene or expressing a
      truncated form (lacking the cytosolic domain) of this protein. Factor VIIa
      stimulated in a dose-dependent manner the growth of the 3 types of fibroblasts,
      thus showing that TF is not involved in the mitogenic activity of factor VIIa.
      The mitogenic activity of factor VIIa disappeared in serum immunopurified in
      factor X and was almost totally inhibited by DX9065, a selective factor Xa
      inhibitor, showing that this effect of factor VIIa occurred via factor Xa
      generated during the incubation period. Hirudin did not show any significant
      effect on factor VIIa-induced fibroblast proliferation, thus showing that the
      effect observed for factor VIIa was selectively mediated by factor Xa and was not
      due to thrombin formation. Our results therefore represent the first evidence for
      the possible importance of factor Xa in the mitogenic effect of factor VIIa and
      show the negligible role of tissue factor in this process.

PMID- 11243845
TI  - Cloning and Expression of Guanylin from the European eel (Anguilla anguilla).
AB  - Extracts of intestinal epithelia from the European eel (Anguilla anguilla)
      stimulated cGMP production in the T84 human colon carcinoma cell line which
      suggested the presence of a guanylin-like peptide in this teleost fish.
      Degenerate oligonucleotide primers were subsequently used in RT-PCR resulting in
      the amplification, cloning, and sequencing of two cDNAs which represent possible
      5' spliceoforms of an eel homologue of the mammalian peptide, guanylin. Northern
      blotting indicated that the main site of expression of the eel peptide is in the
      intestine with much lower signals also detected in the kidney. Intestinal
      expression of guanylin mRNA is up-regulated in both nonmigratory "yellow" and the
      more sexually mature, migratory "silver" eels following acclimation to the
      seawater environment. These results suggest that this peptide signalling system
      may play a role in osmoregulation in euryhaline teleost fish during migration
      between the marine and freshwater environments.

PMID- 11243846
TI  - Expression of the melanocortin 5 receptor on rat lymphocytes.
AB  - The expression of melanocortin-5 receptor (MC5-R) mRNA and protein was
      characterized from isolated rat lymphocytes. The presence of MC5-R mRNA in spleen
      and thymus tissues was demonstrated by RT-PCR. The RT-PCR product was sequenced
      to confirm the identification of MC5-R. Tissues from lachrymal glands, adipose,
      adrenals, thymus, pancreas, and isolated splenic lymphocytes were detergent
      solubilized. The crude proteins were resolved by SDS-PAGE, transblotted to a
      nitrocellulose membrane, and probed for MC5-R using anti-receptor rabbit
      antisera. Two different types of polyclonal rabbit antisera were raised against
      synthetic peptides representing epitopes found at the amino (alphaN-MC5-R) and
      the carboxyl termini (alphaC-MC5-R) on the MC5-R. A prominent band at 77,000
      (p77) was detected in all tissues except the pancreas. Preimmune sera did not
      detect p77 by Western analysis and the addition of peptide antigen neutralized
      the detection of p77 by the specific antisera. The receptor protein was purified
      from spleen and thymic lymphocytes using protein A agarose that precipitated
      material complexed to alphaN-MC5-R. The purified MC5-R was detected by Western
      analysis using alphaC-MC5-R. Both anti-receptor antisera, alphaN-MC5-R and alphaC
      MC5-R, detected the p77. The p77 was treated with protein endoglycosidase F to
      produce a smaller protein band between 34-38,000 (p35); the inferred size is
      37,000 based on the cDNA sequence. The data suggest that Asn-linked carbohydrate
      groups account for much of the p77 mass of the MC5-R. The data also demonstrate
      the expression of MC5-R protein on rat lymphocytes, thus, supporting the
      hypothesis that MC5-R is the ACTH receptor on lymphocytes.

PMID- 11243847
TI  - Aryl hydrocarbon receptor (AhR)-mediated induction of xanthine oxidase/xanthine
      dehydrogenase activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an environmental contaminant, induced
      xanthine oxidase and xanthine dehydrogenase (XO/XDH) activities, in addition to
      ethoxyresorufin-O-dealkylase and methoxyresorufin-O-dealkylase activities in
      liver of mice. When TCDD was given to mice as a single oral dose of 40 microg/kg,
      the activities of XO and XDH increased about threefold within 3 days and the
      increased levels were maintained for 4 weeks. The treatment of mice with 3
      methylcholanthrene also induced XO/XDH activities, but phenobarbital and
      dexamethasone had no effect. The level of aldehyde oxidase, a molybdenum
      flavoenzyme related to XO/XDH, in mouse liver was also enhanced about 1.5-fold by
      TCDD treatment. The inducing effect of TCDD and 3-methylcholanthrene was not
      observed in null mice (AhR(-/-)), which lack the AhR gene. XO and XDH activities
      were induced by TCDD in heterozygous mice (AhR(+/-)). The lipid peroxidation in
      liver was stimulated by TCDD. The induction of XO and XDH, which produces
      reactive oxygen species, may contribute to the various toxicities of TCDD.

PMID- 11243848
TI  - Interaction between Smad anchor for receptor activation and Smad3 is not
      essential for TGF-beta/Smad3-mediated signaling.
AB  - Regulation of subcellular localization of Smad proteins is supposed to be
      critical for the effective initiation and maintenance of TGF-beta signaling.
      Recently, Smad anchor for receptor activation (SARA) has been identified as a
      Smad2 binding protein. SARA regulates the subcellular localization of Smad2 and
      is required for TGF-beta/Smad2-mediated signaling. In this study, we determined
      whether the interaction between SARA and Smad3 is essential for TGF-beta/Smad3
      mediated signaling. We found that a mutant Smad3 (Smad3NS) that lacked the
      binding to SARA was phosphorylated by TGF-beta type I receptor at the similar
      level to that in wild-type Smad3 (Smad3WT). Smad3NS also formed complexes with
      Smad4 and translocalized into the nucleus. Moreover, Smad3NS and Smad3WT equally
      enhanced TGF-beta-induced transcription. Therefore, these findings indicate that,
      in contrast to SARA/Smad2 interaction, SARA/Smad3 interaction is not essential
      for TGF-beta/Smad3-mediated signaling.

PMID- 11243849
TI  - Human rad21 gene, hHR21(SP), is downregulated by hypoxia in human tumor cells.
AB  - To identify genes differentially expressed under normoxic (21% O(2)) or hypoxic
      (1% O(2)) conditions, we used the technique of mRNA differential display using
      total RNA extracted from Chang human liver cells. Among downregulated genes by
      hypoxia, we focused on hHR21(SP) (human homologue of rad21 S. pombe) that is
      involved in DNA double-strand break repair. Northern blot analysis revealed that
      mRNA expression of hHR21(SP) was inhibited by hypoxia in various tumor cell
      lines, such as HepG2, SKHep1, MCF7, and HT1080 cells. We also found that
      hypoglycemia and heat shock significantly decreased the hHR21(SP) level,
      indicating that a DNA double-strand break repair gene, hHR21(SP) might be
      regulated by environmental stresses. In addition, wortmannin, a DNA-dependent
      protein kinase (DNA-PK) inhibitor, decreased the level of hHR21(SP) mRNA,
      indicating that DNA-PK might be involved in the regulation of hHR21(SP). These
      results propose a new understanding of hHR21(SP) regulations in human tumor
      cells.

PMID- 11243850
TI  - Effect of cimetidine on intratumoral cytokine expression in an experimental
      tumor.
AB  - To evaluate the immunomodulatory effects of histamine in vivo, we analyzed an
      experimental syngenic tumor model using a colon adenocarcinoma cell line, CT-26,
      in Balb/c mice. In this model, distinct tumor growth was observed around 6 days
      after inoculation. Daily administration of cimetidine (0.12 mg/kg/day)
      significantly suppressed the increases in tumor volume and weight. On day 6 and
      day 7, histidine decarboxylase (HDC) activity was markedly increased. To examine
      the alterations in the local immune system, the cytokine expressions in the tumor
      tissue were measured by ribonuclease protection assay. The cytokine expression
      levels such as lymphotoxin-beta, tumor necrosis factor-alpha, interferon-gamma,
      interleukin-10, and interleukin-15 were considerably lower in tissues on day 14
      than those on day 6. These decreased expressions were all restored by cimetidine.
      These results indicated that the effects of cimetidine on tumor growth in this
      model might be mediated by restoration of the decreased local cytokine
      expression, which exerts antitumoral effects.

PMID- 11243851
TI  - Effect of serial passage on gene expression in MC3T3-E1 preosteoblastic cells: a
      microarray study.
AB  - The osteoblastic function of mouse preosteoblastic MC3T3-E1 cells, as measured by
      alkaline phosphatase activity and osteocalcin secretion, decreases after serial
      passage. To uncover genes responsible for decreased osteoblastic function in high
      passage cells, we have studied passage-dependent change of gene expression in
      MC3T3-E1 cells. Changes in the expression pattern of 2000 selected genes were
      examined simultaneously by comparing mRNA levels between MC3T3-E1 cells at
      passage 20 and passage 60 using the cDNA microarray analysis. Significant changes
      in the steady-state abundance of 27 mRNAs were observed in response to different
      passage numbers, including 17 known genes, 4 ESTs with homology to known genes,
      and 6 genes with no previously described function or homology. Northern blot
      analysis was used to verify and quantify the expression of selected genes, and
      revealed a significant higher level of up- and down-regulation compared to
      microarray data. These results indicate the existence of a significant change in
      gene expression in osteoblastic cells undergoing serial passages. Such changes
      might be responsible for a reduction in bone regeneration in older osteoblasts.
      Potential roles of selected genes in bone aging are discussed.

PMID- 11243852
TI  - Hematein inhibits tumor necrotic factor-alpha-induced vascular cell adhesion
      molecule-1 and NF-kappaB-dependent gene expression in human vascular endothelial
      cells.
AB  - Monocyte adhesion to the endothelium via adhesion molecules is one of the
      earliest events in atherogenesis. It has been suggested that vascular cell
      adhesion molecule-1 (VCAM-1) plays a very important role in the recruitment of
      monocytes in atherosclerosis. The aim of our study was to evaluate whether
      hematein can influence the expression of VCAM-1 and the transcription of nuclear
      factor-kappaB (NF-kappaB)-dependent genes. Immunohistochemistry revealed that
      mouse aortic artery endothelial cells express VCAM-1 after feeding a high
      cholesterol diet for 8 weeks. Hematein dose dependently suppressed TNF-alpha
      induced VCAM-1 in both surface (30.8%) and soluble protein (65%) production in
      HUVECs. The transcription level of VCAM-1 was measured by Northern blot analysis,
      and decreased VCAM-1 protein expression was associated with a reduction of VCAM-1
      mRNA expression. Transient transfection study of NF-kappaB promoter construct and
      electrophoretic mobility shift assay suggested that hematein inhibited both NF
      kappaB-dependent gene expression and NF-kappaB activation induced by TNF-alpha.
      Our results suggest that the down-regulation of VCAM-1 expression by hematein may
      in part be due to the inhibition of NF-kappaB-dependent gene expression.

PMID- 11243853
TI  - Purkinje cell-specific and inducible gene recombination system generated from
      C57BL/6 mouse ES cells.
AB  - Spatiotemporally restricted gene targeting is needed for analyzing the functions
      of various molecules in a variety of biological phenomena. We have generated an
      inducible cerebellar Purkinje cell-specific gene targeting system. This was
      achieved by establishing a mutant mouse line (D2CPR) from a C57BL/6 mouse ES cell
      line, which expressed a fusion protein consisting of the Cre recombinase and the
      progesterone receptor (CrePR). The Purkinje cell-specific expression of CrePR was
      attained by inserting CrePR into the glutamate receptor delta2 subunit
      (GluRdelta2) gene, which was expressed specifically in the Purkinje cells. Using
      the transgenic mice carrying the Cre-mediated reporter gene, we showed that the
      antiprogesterone RU486 could induce recombinase activity of the CrePR protein
      specifically in the mature cerebellar Purkinje cells of the D2CPR line. Thus this
      mutant line will be a useful tool for studying the molecular function of mature
      Purkinje cells by manipulating gene expression in a temporally restricted manner.

PMID- 11243854
TI  - The small GTPase Rab4A interacts with the central region of cytoplasmic dynein
      light intermediate chain-1.
AB  - Rab4 belongs to the Rab family of small GTPases involved in the regulation of
      intracellular transport, and has been localized to early endosomes. We have
      employed the yeast two-hybrid system to identify proteins that specifically
      interact with Rab4AQ67L, a GTPase-deficient mutant form of Rab4A. Screening a
      mouse embryo cDNA library identified a clone (M449) that interacted with Rab4A in
      a nucleotide-dependent fashion. Data base searches identified this clone as the
      mouse cytoplasmic dynein light intermediate chain-1 (LIC-1). Based on this
      finding, the full-length equivalent human cytoplasmic dynein LIC-1 was isolated
      by PCR. When Rab4A was overexpressed together with either M449 or dynein LIC-1 in
      HeLa cells, the proteins were found to colocalize in the perinuclear region. We
      characterize the localization of both overexpressed human dynein LIC-1 and the
      endogenous protein with respect to microtubules and show that it concentrates to
      the microtubule-organizing center and mitotic spindle. Additionally, GFPRab4A
      endosomes localize to microtubules and are redistributed by nocodazole treatment.
      This is the first described interaction between cytoplasmic dynein, a retrograde
      motor protein, and a Rab protein.

PMID- 11243855
TI  - Impaired fertility in female mice lacking urinary trypsin inhibitor.
AB  - Urinary trypsin inhibitor (UTI) is a serine proteinase inhibitor that is found in
      blood and urine. To investigate the physiological functions of UTI in vivo, we
      generated UTI-deficient mice by gene targeting. The mice showed no obvious
      abnormalities and appeared healthy. However, the females displayed a severe
      reduction in fertility. Wild-type embryos developed normally when transplanted
      into UTI-deficient female mice, suggesting that UTI-deficient females have a
      normal ability to maintain pregnancy. The number of naturally ovulated oocytes
      from UTI-deficient mice was greatly reduced compared with that from wild-type
      mice. Histologically, oocytes with disorganized corona radiata were frequently
      seen in the ovaries of UTI-deficient mice after hormonal stimulation. When
      ovaries from UTI-deficient mice were transplanted into wild-type mice, pups
      derived from the transplanted ovaries were obtained, suggesting that the ovary of
      UTI-deficient mice functions normally if UTI is supplied from the systemic
      circulation. These results demonstrate that UTI plays an important role in the
      formation of the stable cumulus-oocyte complex that is essential for oocyte
      maturation and ovulation.

PMID- 11243856
TI  - Mitochondrial protein p32 can accumulate in the nucleus.
AB  - Human p32 was first isolated associated with the splicing factor ASF/SF-2. The
      p32 protein is translated as pre-protein from which a mitochondrial import signal
      is cleaved off to create the mature p32. The majority of p32 is consequently
      found in the mitochondria. In this study we investigated extramitochondrial p32.
      An increased nuclear localisation of endogenous p32 was demonstrated as a
      response to leptomycin B or actinomycin D treatment of cells. Mature p32 gene and
      deletion mutants were cloned into enhanced green fluorescence protein reporter
      plasmids. On transfection, EGFP-p32 protein was mainly localised to the cytoplasm
      and to a lesser extent to the nucleus of transfected COS cells. Upon treatment
      with actinomycin D or leptomycin B, the EGFP-p32 protein accumulated in the
      nucleus. Deletion analysis indicated which regions of EGFP-p32 are involved in
      nuclear export and nuclear import.

PMID- 11243857
TI  - Analysis of molecular interactions of the p53-family p51(p63) gene products in a
      yeast two-hybrid system: homotypic and heterotypic interactions and association
      with p53-regulatory factors.
AB  - p51 in the p53 tumor suppressor family, also referred to as p63, encodes multiple
      isoforms including p51A (TAp63gamma) and p51B (TAp63alpha). The p53 protein forms
      a tetramer, and its stability and activity are regulated by molecular association
      with viral and cellular proteins and by biochemical modifications. Using a yeast
      two-hybrid system, the p51A and p51B isoforms were examined for homotypic and
      heterotypic interactions in the p53 family proteins and for their affinity to the
      p53-regulatory factors. Results indicate a homotypic interaction dependent on the
      presumed oligomerization domain of the p51 proteins. The possibility of a weak
      heterotypic interaction between p51 and p73 proteins was suggested, while
      association between p51 and p53 appeared improbable. Furthermore, unlike p53, the
      p51 proteins failed to display an affinity to SV40 large T antigen or MDM2-family
      proteins. Having several features in common with p53, the p51 proteins may
      function in biological processes apart from p53.

PMID- 11243858
TI  - Characterization of a gene encoding a Pichia pastoris protein disulfide
      isomerase.
AB  - Protein disulphide isomerases belong to the thioredoxin superfamily of protein
      thiol oxidoreductases that have two double-cysteine redox-active sites and take
      part in protein folding in the endoplasmic reticulum (ER). We report here the
      cloning of a Pichia pastoris genomic DNA fragment (2919 bp) that encodes the full
      length of a protein disulphide isomerase (PpPDI). The deduced amino acid sequence
      of PDI consists of 517 residues and carries the two characteristic PDI-type redox
      active domains -CGHC-, separated by 338 residues, and two potential N
      glycosylation sites. The N-terminal end forms a putative signal sequence, and an
      acidic C-terminal region represents a possible calcium-binding domain. Together
      with the -HDEL ER retrieval sequence at the C-terminus, these features indicate
      that the gene encodes a redox-active ER-resident protein disulphide isomerase.
      The nucleotide sequence, which also contains two other open reading frames, has
      been submitted to the EMBL Nucleotide Sequence Database, Accession No. AJ302014.

PMID- 11243859
TI  - The tissue distribution and functional characterization of human VR1.
AB  - The irritant action of capsaicin is mediated by the vanilloid receptor, VR1,
      which is expressed in sensory neurons termed nociceptors. Capsaicin also
      desensitizes nociceptors and, thus, is useful clinically as an analgesic. Given
      the potential importance of VR1 in pain, we have cloned the human capsaicin
      receptor, hVR1, from a human dorsal root ganglia (DRG) cDNA library. Human VR1
      protein is 85% identical to the rat VR1 and many of the amino acid differences
      are concentrated at the amino and carboxyl termini. VR1 is expressed in DRG as an
      approximately 4.2 kilobase RNA, and is also expressed in the central nervous
      system and in the kidney. Capsaicin (EC(50) = 853 nM), low pH (<5.5), and noxious
      heat (44 degrees C) activate hVR1 expressed in Xenopus oocytes. Subthreshold pH
      (6.4) sensitizes VR1 to capsaicin (EC(50) = 221 nM). This study demonstrates the
      similarity of human and rat VR1 in integrating multiple noxious stimuli.

PMID- 11243860
TI  - Insulinomimetic bis(maltolato)zinc(II) complex: blood glucose normalizing effect
      in KK-A(y) mice with type 2 diabetes mellitus.
AB  - High blood glucose levels of KK-A(y) mice with type 2 diabetes mellitus were
      normalized by daily intraperitoneal (ip) administration of a zinc(II) complex,
      bis(maltolato)zinc(II) (Zn(Mal)(2)) with a Zn(O(4)) coordination mode, following
      the finding of strong in vitro insulinomimetic activity in isolated rat
      adipocytes treated with epinephrine in terms of the inhibition of free fatty acid
      release. The blood glucose level was maintained in the normal range during
      administration of the Zn(Mal)(2) complex for 14 days and improvements in the
      glucose tolerance were confirmed by an oral glucose tolerance test.

PMID- 11243861
TI  - Photodynamic effect of deuteroporphyrin IX and hematoporphyrin derivatives on
      single neuron.
AB  - The photodynamic effects of 6 new deuteroporphyrin IX derivatives with different
      amphiphilicity and lipophilicity, as well as effects of known hematoporphyrin
      derivatives Photofrin II and Photoheme on isolated crayfish mechanoreceptor
      neurons were studied. After 30 min photosensitization, neurons were irradiated
      with He-Ne laser (632.8 nm, 0.3 W/cm(2)), and changes in their firing frequency
      were recorded. Neuron firing was shown to be very sensitive to photodynamic
      effect of the studied deuteroporphyrin IX derivatives causing irreversible firing
      abolition at pikomolar concentrations while Photoheme and Photofrin II were
      effective in the nanomolar range. The most effective sensitizers were 4-(1-methyl
      3-hydroxybutyl)- and 4-(1-methyl-2-acetyl-3-oxobutyl)-deuteroporphyrins.
      Extinction and amphiphilicity were shown to be the most important properties
      determining photodynamic efficiency of the studied photosensitizers.

PMID- 11243862
TI  - Expression of p22-phox and gp91-phox, essential components of NADPH oxidase,
      increases after myocardial infarction.
AB  - Recent studies have shown that oxidative stress plays an important role in
      cardiovascular diseases. NADPH oxidase is one of the major sources of superoxide
      anions and a candidate for the initiation and development of atherosclerosis,
      which involves the remodeling of vasculature. However, the relevance of NADPH
      oxidase in ventricular remodeling has not been well-characterized. This is the
      first report showing that the expression of p22-phox and gp91-phox, essential
      components of NADPH oxidase, are increased in the infarcted sites after
      myocardial infarction. The levels of thiobarbituric acid reactive substance,
      which indicates the lipid peroxidation level, and nuclear factor-kappaB (NF
      kappaB) DNA binding activity are also increased in infarcted sites. Our results
      suggest that the increased expression of NADPH oxidase may have an effect on left
      ventricular remodeling by increasing the redox-sensitive NF-kappaB DNA binding
      activity as well as the lipid peroxidation level.

PMID- 11243863
TI  - Increase in the concentration of carbon 18 monounsaturated fatty acids in the
      liver with hepatitis C: analysis in transgenic mice and humans.
AB  - Steatosis is one of the histologic characteristics of chronic hepatitis C and is
      well reproduced in a transgenic mouse model for hepatocellular carcinoma (HCC) in
      which the core protein of hepatitis C virus (HCV) plays a pivotal role in
      inducing steatosis and HCC. In the present study, the lipid composition in the
      liver of the HCV core gene transgenic mice as well as in those of chronic
      hepatitis C patients was determined. The concentration of carbon 18
      monounsaturated (C18:1) fatty acids, such as oleic and vaccenic acids, which are
      known to increase membrane fluidity leading to higher cell division rates,
      significantly increased in the livers of transgenic mice compared to
      nontransgenic control mice. The concentration of C18:1 fatty acids also
      significantly increased in the livers of chronic hepatitis C patients compared to
      subjects without HCV infection. These results suggest that HCV may affect a
      specific pathway in the lipid metabolism and cause steatosis in the liver.

PMID- 11243864
TI  - Reduction in cyclin D1/Cdk4/retinoblastoma protein signaling by CRE-decoy
      oligonucleotide.
AB  - We have previously demonstrated that the activation of p53 signaling may
      contribute to tumor growth inhibition by the CRE-decoy oligonucleotide containing
      CRE sequence (5'-TGACGTCA-3') (Lee et al., Biochemistry 39, 4863-4868, 2000).
      However, growth inhibition by CRE-decoy treatment was also observed in tumor
      cells containing a mutant p53 (Park et al., J. Biol. Chem. 274, 1573-1580, 1999).
      To understand additional mechanisms of the decoy oligonucleotide, we investigated
      the effect on cyclin D1 expression and a cyclin D1/Cdk4/retinoblastoma protein
      (pRB) signaling pathway. Here we show that in MCF7 breast cancer cells the CRE
      decoy competed with cyclin D1-CRE (5'-TAACGTCA-3') for binding transcription
      factors and reduced cyclin D1 gene expression (in reporter gene assay, Northern
      blotting and Western blotting) to modulate cyclin D1/Cdk4/pRB signaling and G1-S
      progression in a steady state and/or under estrogen stimulation. Decrease of
      cyclin D1 protein level by CRE-decoy treatment was also observed in p53-mutated
      cancer cells. Cyclin D1 expression was also diminished in MCF7 cells stably
      expressing dominant negative mutant CREB indicating that the nonspecific effect
      of oligonucleotide or its degradation products could be excluded. These data
      suggest that inhibition of cyclin D1 expression contributes to the growth
      inhibition induced by the decoy oligonucleotide in MCF7 cells through a cyclin
      D1/Cdk4/pRB signaling pathway. Downregulation of cyclin D1 expression also
      provides a mechanism of CRE-decoy-induced growth inhibition in tumor cells having
      p53 mutation.

PMID- 11243865
TI  - Upregulation of Ghrelin expression in the stomach upon fasting, insulin-induced
      hypoglycemia, and leptin administration.
AB  - Ghrelin is a novel gut-brain peptide that binds to the growth hormone
      secretagogue receptor (GHS-R), thereby functioning in the regulation of growth
      hormone (GH) release and food intake. Ghrelin-producing cells are most abundant
      in the oxyntic glands of the stomach. The regulatory mechanism that governs the
      biosynthesis and secretion of ghrelin has not been clarified. We report that
      ghrelin mRNA expression in the gastric fundus was increased, but that ghrelin
      peptide content decreased after a 48-h fast. Both values returned to control
      levels after refeeding. The ghrelin plasma concentration in the gastric vein and
      systemic venous blood increased after 24- and 48-h fasts. Furthermore, des
      octanoylated ghrelin and n-octanoylated ghrelin were found in rat stomach, with
      the ratio of des-octanoylated ghrelin to n-octanoylated ghrelin markedly
      increased after fasting. The ghrelin mRNA level in the stomach also increased
      after administration of insulin and leptin. Conversely, db/db mice, which are
      deficient in the leptin receptor, had lower ghrelin mRNA levels than control
      mice. These findings suggest that this novel gastrointestinal hormone plays a
      role in the regulation of energy balance.

PMID- 11243866
TI  - Synaptotagmin-like protein 1-3: a novel family of C-terminal-type tandem C2
      proteins.
AB  - Synaptotagmins (Syt), rabphilin-3A, and Doc2 belong to a family of carboxyl
      terminal type (C-type) tandem C2 proteins and are thought to be involved in
      vesicular trafficking. We have cloned and characterized a novel family of C-type
      tandem C2 proteins, designated Slp1-3 (synaptotagmin-like protein 1-3). The Slp1
      3 C2 domains show high homology to granuphilin-a C2 domains, but the amino
      terminal domain of Slp1-3 does not contain any known protein motifs or a
      transmembrane domain. A subcellular fractionation study indicated that Slp1-3
      proteins are peripheral membrane proteins. Phospholipid binding experiments
      indicated that Slp3 is a Ca(2+)-dependent isoform, but Slp1 and Slp2 are Ca(2+)
      independent isoforms, because only the Slp3 C2A domain showed Ca(2+)-dependent
      phospholipid binding activity. The C-terminus of Slp1-3 also bound neurexin
      Ialpha in vitro, in the same manner as Syt family proteins, which may be
      important for the membrane association of Slp1-3. In addition, Slp family
      proteins are differentially distributed in different mouse tissues and at
      different developmental stages.

PMID- 11243868
TI  - Regulation of activating transcription factor-2 in early stage of the adipocyte
      differentiation program.
AB  - p38beta mitogen-activated protein kinase activity is required for the
      differentiation of 3T3-L1 fibroblasts into adipocytes. Activating transcription
      factor-2 (ATF-2) is efficiently phosphorylated and activated by p38beta kinase.
      These findings led us to examine a regulatory role of ATF-2 in adipocyte
      differentiation. The induction of ATF-2 protein precedes the expression of the
      transcription factors, peroxisome proliferator-activated receptor (PPAR) gamma
      and CCAAT/enhancer-binding protein (C/EBP) alpha. Consistent with early
      activation of p38beta kinase, the phosphorylation of ATF-2 was also detected in
      early stage of adipocyte differentiation. ATF-2 regulated gene transcription of
      PPARgamma, which was synergistically enhanced by p38beta kinase and C/EBPbeta
      proteins expression. Ectopic expression of ATF-2 in 3T3-L1 cells induced the
      endogenous PPARgamma protein levels. These results suggest that ATF-2 plays a
      role in a primary regulator of adipocyte differentiation with C/EBPbeta through
      promoting adipogenesis-inducing transcription factors including PPARgamma and
      becomes associated earlier in the differentiation program as mitotic clonal
      expansion proceeds and the cells become initially differentiated.

PMID- 11243869
TI  - Identification of an alternatively spliced form of the mouse AML1/RUNX1 gene
      transcript AML1c and its expression in early hematopoietic development.
AB  - Acute myeloid leukemia 1 (AML1: or runt-related transcription factor, RUNX1)
      encodes the DNA binding subunit of the heterodimering transcription factor
      complex PEBP2 (CBF), which plays an essential role for definitive hematopoiesis.
      Transcription of AML1 is controlled by two distinct promoter regions, which
      results in the generation of the respective AML1b and AML1c isoforms. Here we
      report the isolation of the mouse homologue of human AML1c, whose unique N
      terminus is 100% identical at the amino acid level to its human counterpart and
      63 and 37% identical to the respective family members AML2 and AML3.
      Semiquantitative RT-PCR assay on mouse embryonic stem cell clones during in vitro
      differentiation and Northern blot analysis of a mouse embryo revealed that AML1b
      is expressed in undifferentiated ES cells and upregulated in the early
      developmental stage, in contrast to the gradual upregulation and steady
      maintenance of AML1c expression during embryogenesis. In addition, maintenance of
      AML1c expression depended on the presence of active AML1 allele(s) while that of
      AML1b did not. Thus, these two AML1 isoforms driven by their respective promoters
      are differentially expressed and are likely to have distinct functions in early
      hematopoietic development.

PMID- 11243867
TI  - Msx1 gene overexpression induces G1 phase cell arrest in human ovarian cancer
      cell line OVCAR3.
AB  - Recent evidence suggested an involvement of homeobox genes in tumorigenesis. Here
      we investigated whether one of homeobox-containing genes, Msx1, might be involved
      in the regulation of cell proliferation and cell cycle using Msx1 overexpressing
      human ovarian cancer cell line, OVCAR3. Overexpression of Msx1 in OVCAR3 cells
      inhibited cell proliferation by markedly increasing the length of the G1 phase of
      the cell cycle over control cells. Consistent with this result, dramatic
      suppression of cyclins D1, D3, E, cyclin-dependent kinase 4, c-Jun, and Rb was
      observed. Elevated expression of genes involved in the growth arrest and
      apoptosis (GADD153 and apoptotic cystein protease MCH4) and suppression of
      proliferation associated protein gene (PAG) in Msx1-overexpressing cells by cDNA
      expression array analysis provide further evidence for a potential repressor
      function of Msx1 in cell cycle progression.

PMID- 11243871
TI  - Molecular cloning of actinohivin, a novel anti-HIV protein from an actinomycete,
      and its expression in Escherichia coli.
AB  - Syncytium-inducing variants of the HIV-1 virus are correlated with poor diagnosis
      and rapid disease progression. We have recently discovered a novel anti-HIV
      protein, referred to as actinohivin, that inhibits syncytium formation. Here we
      describe the cloning and sequencing of the gene encoding actinohivin from the
      actinomycete strain K97-0003, and its expression in Escherichia coli. The
      actinohivin gene was located on a 0.8-kb BamHI fragment of genomic DNA. The
      fragment contained an open reading frame of 480 bp, which encoded a protein of
      160 amino acids with calculated molecular weight of 17492.7. The N-terminal
      region was found to be a typical signal peptide of prokaryotes, and actinohivin
      was located at amino acid positions 46-160. The actinohivin gene could be
      expressed in E. coli using a pET30Xa/LIC expression vector and the purified
      recombinant actinohivin was found to inhibit syncytium formation to a similar
      extent as actinohivin from its natural source.

PMID- 11243870
TI  - A single nucleotide polymorphism of CYP2b6 found in Japanese enhances catalytic
      activity by autoactivation.
AB  - A single nucleotide polymorphism (SNP) resulting in a substitution from Gln to
      His was found in exon 4 of the CYP2B6 gene in Japanese. The frequency of the
      variant allele was found to be 19.9%. The mutant- and the wild-type enzymes were
      expressed in Escherichia coli, and the effects of the single amino acid
      substitution on the catalytic activity were examined by investigating the kinetic
      profiles of 7-ethoxycoumarin O-deethylase activity. The wild-type enzyme showed
      typical Michaelis-Menten kinetics, while the mutant-type enzyme represented the
      sigmoidal kinetics with a higher V(max) value compared to that of the wild-type
      enzyme. Eadie-Hofstee plots further revealed an existence of allosteric effects
      for the reaction catalyzed by the variant. This is the first evidence
      demonstrating that only one amino acid substitution, Gln172His, caused by natural
      SNP enhances the catalytic activity of CYP by obtaining the character of
      homotropic cooperativity.

PMID- 11243872
TI  - Fe(III) binding to Bacillus PS3 F(1)ATPase, alphabeta subcomplexes and isolated
      alpha- and beta-subunits.
AB  - Isolated alpha- and beta-subunits of Thermophilic Bacillus PS3 F(1)ATPase (TF(1))
      bind about 1 Fe(III) equivalent. Upon reassembling in the symmetric
      alpha(3)beta(3) hexamer, Fe(III) binding capacity decreases, as this complex
      binds about three Fe(III) equivalents. In accordance, when the hexamer is
      dissociated in the alpha(1)beta(1) heterodimer, each heterodimer binds about one
      Fe(III) equivalent. On the contrary, native TF(1) exhibits a single Fe(III) site.
      CD spectra in far UV indicate that upon Fe(III) binding both the whole complex
      and the isolated beta-subunit undergo structural modifications accompanied by
      decrease of alpha-helix content, while alpha-subunit doesn't. As in
      alpha(3)beta(3) and in the whole enzyme the number of bound Fe(III) equivalents
      is consistent with the number of beta-subunits in the "empty" conformation, it is
      inferred that the single Fe(III) site in TF(1) is probably located in beta(E).

PMID- 11243873
TI  - Alteration of inhibitory properties of Pleurotus ostreatus proteinase A inhibitor
      1 by mutation of its C-terminal region.
AB  - Pleurotus ostreatus proteinase A inhibitor 1 (POIA1), which is composed of 76
      residues without disulfide bridges, is a unique inhibitor in that it exhibits
      sequence similarity to the propeptides of subtilisins. In order to elucidate the
      inhibitory mechanism of POIA1, we constructed an expression system for a
      synthetic POIA1 gene. The wild-type POIA1 was found to inhibit subtilisin BPN'
      with an inhibitor constant (K(i)) of 3.2 x 10(-9) M, but exhibited a time
      dependent decrease of inhibitory activity as a consequence of degradation by the
      protease, showing that the wild-type POIA1 was a temporary inhibitor when
      subtilisin BPN' was used as a target protease. Since POIA1 shows sequence
      similarity to the propeptide of subtilisin, which is known to inhibit the
      protease via its C-terminal region, the C-terminal six residues of POIA1 were
      replaced with those of the propeptide of subtilisin BPN'. The mutated POIA1
      inhibited subtilisin BPN' with a K(i) value of 2.8 x 10(-11) M and did not
      exhibit time-dependent decrease of inhibitory activity, showing about 100-fold
      increases in binding affinity for, and resistance to, the protease. These results
      clearly indicate that the C-terminal region of POIA1 plays an important role in
      determining the inhibitory activity toward the protease, and that the increase in
      binding ability to the protease is closely related to resistance to proteolytic
      degradation. Therefore, the inhibitory properties of POIA1 can be altered by
      mutation of its C-terminal region.

PMID- 11243874
TI  - A mechanism for the partial insertion of protein kinase C into membranes.
AB  - We propose that the principle driving force allowing protein kinase C (PKC) to
      insert partway into membranes is the transient creation of an interior
      hydrophilic phase within the membrane. We further suggest that this phase is
      composed of non-bilayer-forming elements, such as diacylglycerol or phorbol
      esters. We used the combination of fluorescence resonance energy transfer (using
      fluorescently labeled phospholipid molecules and the endogenous tryptophan
      residues of PKC) and fluorescence quenching by the water-soluble reagent
      potassium iodide. The experimental system used micelles and purified PKC. Our
      model accounts for both the established kinetic data on PKC as well as the
      physical requirements of protein-membrane interaction. Moreover, it establishes
      PKC as the first example of a partially embedded membrane protein, and provides a
      mechanism to account for its activation.

PMID- 11243875
TI  - RNase activity of a DNA minor groove binder with a minimalist catalytic motif
      from RNase A.
AB  - Imidazole and compounds containing imidazole residues have been shown to cleave
      RNA in an RNase A-mimicking manner. Di-imidazole lexitropsin is a compound which
      is derived from the polyamide drugs distamycin and netropsin essentially by the
      replacement of two pyrrole heterocycles with N-methyl-imidazole residues. This
      enables it to bind to the minor groove of B-DNA in a sequence-specific manner. We
      demonstrate here that this lexitropsin derivative has RNA cleavage activity, as
      tested on model RNAs. Optimal cleavage conditions and cleavage specificity
      resemble those known from other imidazole conjugates and are thus consistent with
      an RNase A type cleavage mechanism. The optimum concentration of the compound for
      cleavage is similar to previously investigated imidazole-based RNase mimics. As a
      whole new class of chemical compounds capable of interacting with nucleic acids
      through extensive hydrogen bonding, these imidazole containing compounds
      constitute promising scaffolds and ligands, for the construction of novel RNase
      mimics with high affinity.

PMID- 11243876
TI  - Signaling mechanism underlying COX-2 induction by lysophosphatidylcholine.
AB  - Lysophosphatidylcholine, a component of oxidized low density lipoprotein, is
      critical for pathological conditions including atherosclerosis. However, the
      signaling mechanism of lysophosphatidylcholine remains poorly understood. Here we
      reported that lysophosphatidylcholine induces phosphorylation of p38 and the
      transcription factors, CREB and ATF-1 with concomitant up-regulation of
      cyclooxygenase-2 expression in cultured vascular endothelial cells.
      Lysophosphatidylcholine induced p38 phosphorylation in a time- and concentration
      dependent manner partly via pathway depending on protein tyrosine kinase. Both
      lysophosphatidylcholine-stimulated phosphorylation of CREB and ATF-1 and
      lysophosphatidylcholine-increased expression of cyclooxygenase-2 mRNA and protein
      were effectively inhibited by a combination of SB203580 and PD98059, specific
      inhibitors of p38 and MEK1, respectively, as well as Ro31-8220 and H89, potent
      inhibitors of MSK1. These results suggest that both p38 and ERK may function as
      upstream signaling pathways capable of activating CREB and ATF-1 with subsequent
      induction of cyclooxygenase-2 expression by lysophosphatidylcholine.

PMID- 11243877
TI  - Protease inhibitors divert amyloid precursor protein to the secretory pathway.
AB  - Addition of cysteine protease inhibitors to cells expressing amyloid precursor
      protein (APP) resulted in a >2-fold increase in appearance of the secreted
      extracellular domain of APP in the media. This was accounted for by increased
      flux of APP into the secretory pathway since protease inhibitors also caused a
      twofold increase in newly translated, incompletely glycosylated APP detected by
      pulse-labeling. These results show that a portion of newly translated APP
      molecules are normally rapidly degraded by cysteine protease(s) but can enter the
      secretory pathway when degradation is inhibited. Newly translated APP molecules
      are thus still competent for posttranslational processing in distal cellular
      compartments. Their degradation thus may not result from misfolding but merely
      susceptibility to an endoplasmic reticulum localized cysteine protease.

PMID- 11243878
TI  - Bcl-2 overexpression protects photooxidative stress-induced apoptosis of
      photoreceptor cells via NF-kappaB preservation.
AB  - We recently showed that photooxidative stress on cultured photoreceptor cells
      results in down-modulation of NF-kappaB activity which then leads to apoptosis of
      cultured 661W photoreceptor cells. In an effort to further delineate the
      mechanism of photoreceptor cell death, we sought to determine the effects of Bcl
      2 overexpression on cell survivability. Wild-type 661W cells were transfected
      with the plasmid construct pSFFV-neo-Bcl-2 and several clones were isolated. All
      clones demonstrated increased Bcl-2 mRNA and protein levels, with the B4 clone
      exhibiting the greatest enhancement. On exposure to visible light the B4 cells
      were protected from undergoing apoptosis when compared with the mock transfected
      cells, as ascertained by TUNEL apoptosis assay and formazan based estimation of
      cell viability. The Bcl-2 overexpressing cells also maintained a higher Bcl-2/Bax
      ratio, suggesting that this ratio is important in protection from photooxidative
      stress. Electrophoretic mobility shift assays for NF-kappaB demonstrated higher
      activity in both nuclear and cytosolic fractions of the B4 photoreceptors
      compared with the 661W wild-type cells at all light exposure time points.
      Furthermore, the findings of the gel shift assays were further supported by
      immunocytochemistry for NF-kappaB which revealed that protein levels of the RelA
      subunit of NF-kappaB were protected in the nucleus as well as in the cytoplasm of
      Bcl-2 overexpressing B4 cells exposed to light compared to the 661W cells. These
      results suggest that Bcl-2 overexpression protects NF-kappaB protein levels and
      activity in the nucleus, indicating that preservation of NF-kappaB binding
      activity in the nucleus may be essential for photoreceptor cells to survive
      photooxidative damage induced apoptosis.

PMID- 11243879
TI  - ASK1-signaling promotes c-Myc protein stability during apoptosis.
AB  - We previously reported that JNK is involved in the regulation of c-Myc-mediated
      apoptosis triggered by UV irradiation and anticancer drug treatment. Here we show
      that ASK1 is an upstream regulator for c-Myc-mediated apoptosis triggered by UV,
      and we found a direct role for Ser-62 and Ser-71 in the regulation of protein
      stability and function of c-Myc. The ASK1-JNK pathway enhanced the protein
      stability of c-Myc through phosphorylation at Ser-62 and Ser-71, which was
      required for c-Myc-dependent apoptosis by ASK1-signaling. Interestingly, ASK1
      signaling attenuated the degradation of ubiquitinated c-Myc without affecting the
      ubiquitination process. Together, these findings indicate that the ASK1-JNK
      pathway promotes the proapoptotic activity of c-Myc by modulating c-Myc protein
      stability through phosphorylation at Ser-62 and Ser-71.

PMID- 11243880
TI  - The dipeptide, gamma-glutamylcysteine, is recognized by the anti-glutathione
      antibody single chain Fv fragment 20C9.
AB  - The anti-glutathione antibody scFv 20C9, which we previously isolated from a
      human synthetic phage antibody scFv library [Hirose, M., Hayano, T., Shirai, H.,
      Nakamura, H., and Kikuchi, M. (1998) Protein Eng. 11, 243-248], was expressed in
      the E. coli pET system and purified by sequential chromatography on Ni and
      glutathione-conjugated affinity resins. The purified scFv 20C9 antibody was
      characterized for its binding affinity for several glutathione derivatives by the
      BIACORE system. Although GSH, GSSG, and gamma-Glu-Cys could bind to the
      immobilized antibody, this was not the case for Cys-Gly, l-Glu, l-Cys, l-Gly, or
      several other glutathione derivatives such as gamma-Glu-Ser-Gly. The results
      suggest that a gamma-glutamic acid and sulfur atom are important for scFv 20C9
      antibody recognition of glutathione. This is the first report to indicate that an
      scFv antibody can recognize a region as small as a dipeptide.

PMID- 11243881
TI  - Biochemical characterization of cholesterol-3-sulfate as the sole effector for
      the phosphorylation of HMG1 by casein kinase I in vitro.
AB  - Phosphorylation of high mobility group protein 1 (HMG1) by casein kinase I (CK-I)
      and potent effectors (inhibitors and activators) of this phosphorylation were
      investigated in vitro. We found that (i) CK-I phosphorylates specifically
      threonine residues on HMG1 when incubated with cholesterol-3-sulfate (CH-3S), but
      no phosphorylation of HMG1 is detected in the presence of other cholesterol
      related compounds or their sulfated derivatives; (ii) this phosphorylation is
      selectively inhibited by heparin, but stimulated significantly by 3',4',7
      trihydroxy-isofavone at low doses (0.1-3 microM); and (iii) CH-3S directly
      induces a drastic conformational change in HMG1. The latter finding provides a
      mechanism to explain how CH-3S alone can induce the phosphorylation of HMG1 by CK
      I in vitro.

PMID- 11243882
TI  - The transcription factors NF-kappab and AP-1 are differentially regulated in
      skeletal muscle during sepsis.
AB  - Sepsis is associated with increased muscle proteolysis and upregulated
      transcription of several genes in the ubiquitin-proteasome proteolytic pathway.
      Glucocorticoids are the most important mediator of sepsis-induced muscle
      cachexia. Here, we examined the influence of sepsis in rats on the transcription
      factors NF-kappaB and AP-1 in skeletal muscle and the potential role of
      glucocorticoids in the regulation of these transcription factors. Sepsis was
      induced by cecal ligation and puncture (CLP). Control rats were sham-operated. NF
      kappaB and AP-1 DNA binding activity was determined by electrophoretic mobility
      shift assay (EMSA) in extensor digitorum longus muscles at different time points
      up to 16 h after sham-operation or CLP. Sepsis resulted in an early (4 h)
      upregulation of NF-kappaB activity followed by inhibited NF-kappaB activity at 16
      h. AP-1 binding activity was increased at all time points studied during the
      septic course. When rats were treated with the glucocorticoid receptor antagonist
      RU38486, NF-kappaB activity increased, whereas AP-1 activity was not influenced
      by RU38486. The results suggest that NF-kappaB and AP-1 are differentially
      regulated in skeletal muscle during sepsis and that glucocorticoids may regulate
      some but not all transcription factors in septic muscle.

PMID- 11243883
TI  - Enhancement of lysophosphatidic acid-induced ERK phosphorylation by phospholipase
      D1 via the formation of phosphatidic acid.
AB  - We made stable cell lines overexpressing PLD1 (GP-PLD1) from GP+envAm12 cell, a
      derivative of NIH 3T3 cell. PLD1 activity and extracellular signal-regulated
      kinase (ERK) phosphorylation were enhanced in GP-PLD1 cells by the treatment of
      lysophosphatidic acid (LPA). In contrast, these LPA-induced effects were
      attenuated with the pretreatment of pertussis toxin (PTX) or protein kinase C
      (PKC) inhibitor. Moreover, accumulation of phosphatidic acid (PA), a product of
      PLD action, potentiated the LPA-induced ERK activation in GP-PLD1 cells while
      blocking of PA production with the treatment of 1-butanol attenuated LPA-induced
      ERK phosphorylation. From these results, we suggest that LPA activate PLD1
      through pertussis toxin-sensitive G protein and PKC-dependent pathways, then PA
      produced from PLD1 activation facilitate ERK phosphorylation.

PMID- 11243884
TI  - Structure, function, and tissue expression pattern of human SN2, a subtype of the
      amino acid transport system N.
AB  - We have cloned a new subtype of the amino acid transport system N from a human
      liver cell line. This transporter, designated SN2, consists of 472 amino acids
      and exhibits 62% identity with human SN1 at the level of amino acid sequence. SN2
      specific transcripts are expressed predominantly in the stomach, brain, liver,
      lung, and intestinal tract. The sizes of the transcripts vary in different
      tissues, indicating tissue-specific alternative splicing of the SN2 mRNA. In
      contrast, SN1 is expressed primarily in the brain and liver and there is no
      evidence for the presence of multiple transcripts of varying size for SN1. When
      expressed in mammalian cells, the cloned human SN2 mediates Na(+)-coupled
      transport of system N-specific amino acid substrates (glutamine, asparagine, and
      histidine). In addition, SN2 also transports serine, alanine, and glycine.
      Anionic amino acids, cationic amino acids, imino acids, and N-alkylated amino
      acids are not recognized as substrates by human SN2. The SN2-mediated transport
      process is Li(+)-tolerant and highly pH-dependent. The Michaelis-Menten constant
      for histidine uptake via human SN2 is 0.6 +/- 0.1 mM. The gene coding for SN2 is
      located on human chromosome Xp11.23. Successful cloning of SN2 provides the first
      molecular evidence for the existence of subtypes within the amino acid transport
      system N in mammalian tissues.

PMID- 11243885
TI  - Cloning and tissue distribution of a novel human cytochrome p450 of the CYP3A
      subfamily, CYP3A43.
AB  - On the basis of the detection of an expressed sequence tag ('EST') similar to the
      human cytochrome P450 3A4 cDNA, we have identified a novel member of the human
      cytochrome P450 3A subfamily. The coding region is 1512-bp long and shares 84,
      83, and 82% sequence identity on the cDNA level with CYP3A4, 3A5, and 3A7,
      respectively, with a corresponding amino acid identity of 76, 76, and 71%.
      Quantitative real time based mRNA analysis revealed CYP3A43 expression levels at
      about 0.1% of CYP3A4 and 2% of CYP3A5 in the liver, with significant expression
      in 70% of the livers examined. Gene specific PCR of cDNA from extrahepatic
      tissues showed, with the exception of the testis, only low levels of CYP3A43
      expression. The CYP3A43 cDNA was heterologously expressed in yeast, COS-1 cells,
      mouse hepatic H2.35 cells and in human embryonic kidney (HEK) 293 cells, but in
      contrast to CYP3A4 which was formed in all cell types, no detectable CYP3A43
      protein was produced. This indicates a nonfunctional protein or specific
      conditions required for proper folding. It is concluded that CYP3A43 mRNA is
      expressed mainly in liver and testis and that the protein would not contribute
      significantly to human drug metabolism.

PMID- 11243886
TI  - Ultrastructure of the zonula adherens revealed by rapid-freeze deep-etching.
AB  - The zonula adherens (ZA) in adult chicken retinal pigment epithelium was examined
      with cryo-electron microscopic methods. Deep-etching of the cross-fractured ZA
      showed globules in the intercellular space. These globules apparently correspond
      to the electron-dense structure seen in thin sections. Deep-etching of obliquely
      fractured ZA further revealed rod-like structures extending from the
      extracellular surface into the intercellular space. These rods (mean
      approximately 9 nm thick, approximately 20 nm long) were straight and sometimes
      divided into two or three segments. The rods typically canted at approximately 60
      degrees with respect to the plasma membrane, and they were often connected to the
      intercellular globules at their distal ends. When the rods are compared with the
      isolated cadherins reported previously, it is suggested that a combination of a
      rod and a globule may represent an extracellular part of cadherin. Membrane
      particles were observed on the P-face of the ZA plasma membrane, and their
      distribution density was approximately seven times that of the rods. The freeze
      etching also revealed a characteristic particle complex on the ZA cytoplasmic
      surface, which may represent the cytosolic proteins linking cadherins to actin
      bundles.

PMID- 11243887
TI  - Three-dimensional structure of the catalytic core of acetylxylan esterase from
      Trichoderma reesei: insights into the deacetylation mechanism.
AB  - Acetylxylan esterase from Trichoderma reesei removes acetyl side groups from
      xylan. The crystal structure of the catalytic core of the enzyme was solved at
      1.9 A resolution. The core has an alpha/beta/alpha sandwich fold, similar to that
      of homologous acetylxylan esterase from Penicillium purpurogenum and cutinase
      from Fusarium solani. All three enzymes belong to family 5 of the carbohydrate
      esterases and the superfamily of the alpha/beta hydrolase fold. Evidently, the
      enzymes have diverged from a common ancestor and they share the same catalytic
      mechanism. The catalytic machinery of acetylxylan esterase from T. reesei was
      studied by comparison with cutinase, the catalytic site of which is well known.
      Acetylxylan esterase is a pure serine esterase having a catalytic triad (Ser90,
      His187, and Asp175) and an oxyanion hole (Thr13 N, and Thr13 O gamma). Although
      the catalytic triad of acetylxylan esterase has been reported previously, there
      has been no mention of the oxyanion hole. A model for the binding of substrates
      is presented on the basis of the docking of xylose. Acetylxylan esterase from T.
      reesei is able to deacetylate both mono- and double-acetylated residues, but it
      is not able to remove acetyl groups located close to large side groups such as 4
      O-methylglucuronic acid. If the xylopyranoside residue is double-acetylated, both
      acetyl groups are removed by the catalytic triad: first one acetyl group is
      removed and then the residue is reorientated so that the nucleophilic oxygen of
      serine can attack the second acetyl group.

PMID- 11243888
TI  - Enamel biomineralization defects result from alterations to amelogenin self
      assembly.
AB  - Enamel formation is a powerful model for the study of biomineralization. A key
      feature common to all biomineralizing systems is their dependency upon the
      biosynthesis of an extracellular organic matrix that is competent to direct the
      formation of the subsequent mineral phase. The major organic component of forming
      mouse enamel is the 180-amino-acid amelogenin protein (M180), whose ability to
      undergo self-assembly is believed to contribute to biomineralization of
      vertebrate enamel. Two recently defined domains (A and B) within amelogenin
      appear essential for this self-assembly. The significance of these two domains
      has been demonstrated previously by the yeast two-hybrid system, atomic force
      microscopy, and dynamic light scattering. Transgenic animals were used to test
      the hypothesis that the self-assembly domains identified with in vitro model
      systems also operate in vivo. Transgenic animals bearing either a domain-A
      deleted or domain-B-deleted amelogenin transgene expressed the altered amelogenin
      exclusively in ameloblasts. This altered amelogenin participates in the formation
      an organic enamel extracellular matrix and, in turn, this matrix is defective in
      its ability to direct enamel mineralization. At the nanoscale level, the forming
      matrix adjacent to the secretory face of the ameloblast shows alteration in the
      size of the amelogenin nanospheres for either transgenic animal line. At the
      mesoscale level of enamel structural hierarchy, 6-week-old enamel exhibits
      defects in enamel rod organization due to perturbed organization of the precursor
      organic matrix. These studies reflect the critical dependency of amelogenin self
      assembly in forming a competent enamel organic matrix and that alterations to the
      matrix are reflected as defects in the structural organization of enamel.

PMID- 11243889
TI  - Statistical evaluation of colocalization patterns in immunogold labeling
      experiments.
AB  - The ultrastructural localization of various antigens in a cell using antibodies
      conjugated to gold particles is a powerful instrument in biological research.
      However, statistical or stereological tools for testing the observed patterns for
      significant clustering or colocalization are missing. The paper presents a method
      for the quantitative analysis of single or multiple immunogold labeling patterns
      using interpoint distances and tests the method using experimental data. The
      clustering or colocalization of gold particles was detected using various
      characteristics of the distribution of distances between them. Pair correlation
      and cross-correlation functions were used for exploratory analysis; second order
      reduced K (or cross-K) functions were used for testing the statistical
      significance of observed events. Confidence intervals of function values were
      estimated by Monte Carlo simulations of the Poisson process for independent
      particles, and results were visualized in histograms. Furthermore, a suitability
      of K functions modified by censoring or weighting was tested. The reliability of
      the method was assessed by evaluating the labeling patterns of nascent DNA and
      several nuclear proteins with known functions in replication foci of HeLa cells.
      The results demonstrate that the method is a powerful tool in biological
      investigations for testing the statistical significance of observed clustering or
      colocalization patterns in immunogold labeling experiments.

PMID- 11243890
TI  - A transmission electron microscope study using vitrified ice sections of
      predentin: structural changes in the dentin collagenous matrix prior to
      mineralization.
AB  - The assembly of the collagenous organic matrix prior to mineralization is a key
      step in the formation of bones and teeth. This process was studied in the
      predentin of continuously forming rat incisors, using unstained vitrified ice
      sections examined in the transmission electron microscope. Progressing from the
      odontoblast surface to the mineralization front, the collagen fibrils thicken to
      ultimately form a dense network, and their repeat D-spacings and banding patterns
      vary. Using immunolocalization, the most abundant noncollagenous protein in
      dentin, phosphophoryn, was mapped to the boundaries between the gap and overlap
      zones along the fibrils nearest the mineralization front. It thus appears that
      the premineralized collagen matrix undergoes dynamic changes in its structure.
      These may be mediated by the addition and interaction with the highly anionic
      noncollagenous proteins associated with collagen. These changes presumably create
      a collagenous framework that is able to mineralize.

PMID- 11243891
TI  - Quaternary organization of the Staphylothermus marinus phosphoenolpyruvate
      synthase: angular reconstitution from cryoelectron micrographs with molecular
      modeling.
AB  - Digital electron images of frozen-hydrated preparations of the 2.25-MDa
      Staphylothermus marinus phosphoenolpyruvate synthase (EC 2.7.9.2) have been
      analyzed by single-particle classification and averaging and iterative quaternion
      based angular reconstitution. Contrast transfer function correction of
      micrographs obtained at different defocus values was used to improve the
      informational quality of the projection averages. Three-dimensional
      reconstructions were obtained to roughly 3-nm spatial resolution, in which the 24
      identical subunits were arranged to form an octahedral complex, although the
      amino-terminal nucleotide-binding domain was not resolved. An atomic model of the
      subunit was generated by homology modeling using as the reference the known X-ray
      crystallographic structure of the related enzyme pyruvate orthophosphate dikinase
      (EC 2.7.9.1) from Clostridium symbiosum (Protein Data Bank entry 1DIK). The S.
      marinus protein could be arranged into an assembly of 12 homodimers to match the
      three-dimensional reconstruction in terms of shape and size of the homodimers, as
      well as overall shape and size of the complex. The quaternary model indicated
      that active sites of three monomers were localized around cavities (or putative
      channels) centered at the threefold axes of rotational symmetry and that carboxyl
      terminal alpha-helical segments of four monomers were localized at the fourfold
      axes of rotational symmetry where they could facilitate interdimer interaction.
      The quaternary arrangement also indicated numerous potential hydrophobic and
      electrostatic interactions at the interdimer interfaces that could contribute
      further to structural stability.

PMID- 11243892
TI  - Structural analysis of F18 fimbriae expressed by porcine toxigenic Escherichia
      coli.
AB  - The F18 fimbriae expressed by porcine toxigenic Escherichia coli strains are 1-
      to 2-mm-long filaments that mediate the adhesion of the bacteria to enterocytes.
      The backbone of these fimbriae is built from a major structural 15.1-kDa protein,
      FedA. The structure of isolated negatively stained F18 fimbriae imaged by dark
      field scanning transmission electron microscopy (STEM) was resolved to
      approximately 2 nm. Analyzing their helical symmetry showed the axially repeating
      units to alternate in a "zigzag" manner around the helical axis with an axial
      rise of 2.2 nm. Two repeating units give rise to the observed 4.3-nm helical
      repeat, which is practically identical to the pitch of the one-start helix
      formed. Additionally, an axially repeating pattern with a 27-nm spacing was found
      on rotary-shadowed fimbriae. Mass-per-length determination of unstained F18
      fimbriae by STEM revealed the axially repeating unit to have a molecular mass of
      25.4 kDa, indicating that it is a FedA monomer, with the difference in mass
      arising from the minor subunits, FedE and FedF. The presence of the latter two
      proteins might cause the observed 27-nm axial pattern.

PMID- 11243893
TI  - Introduction.

PMID- 11243894
TI  - The role of the SV40 ST antigen in cell growth promotion and transformation.
AB  - The simian virus 40 small-t (ST) antigen plays a key role in permissive and
      nonpermissive infections, increasing virus yields in lytic cycles of primate
      cells and enhancing the ability of large-T (LT) to transform rodent or even human
      cells. In the absence of ST, tumors in rodent model systems appear primarily in
      lymphoid and other proliferative tissues and transformation is reduced in several
      in vitro systems. The functions of ST largely reflect its binding and inhibition
      of protein phosphatase 2A, although a recently described dnaJ domain also
      contributes to its biology. The dnaJ domain is present in LT and a third early
      gene product, the 17kT protein, for which a potential role in transformation
      deserves further evaluation.

PMID- 11243896
TI  - Role of T antigen interactions with p53 in tumorigenesis.
AB  - SV40 induces neoplastic transformation by disabling several key cellular growth
      regulatory circuits. Among these are the Rb- and p53-families of tumor
      suppressors. The multifunctional, virus-encoded large T antigen blocks the
      function of both Rb and p53. Large T antigen uses multiple mechanisms to block
      p53 activity, and this action contributes to tumorigenesis, in part, by blocking
      p53-mediated growth suppression and apoptosis. Since the p53 pathway is
      inactivated in most human tumors, T antigen/p53 interactions offer a possible
      mechanism by which SV40 contributes to human cancer.

PMID- 11243895
TI  - Cellular transformation by SV40 large T antigen: interaction with host proteins.
AB  - SV40 large T antigen (TAg) is a powerful oncoprotein capable of transforming a
      variety of cell types. The transforming activity of TAg is due in large part to
      its perturbation of the retinoblastoma (pRB) and p53 tumor suppressor proteins.
      In addition, TAg binds to several other cellular factors, including the
      transcriptional co-activators p300 and CBP, which may contribute to its
      transformation function. Several other features of TAg that appear to contribute
      to its full transformation potential are yet to be completely understood. Study
      of TAg therefore continues to provide new insights into the mechanism of cellular
      transformation.

PMID- 11243897
TI  - SV40 and cell cycle perturbations in malignant mesothelioma.
AB  - Although epidemiological findings have established that exposure to asbestos
      fibers is the major cause of malignant mesothelioma (MM), recent studies have
      implicated simian virus 40 (SV40) in the etiology of some of these tumors.
      Cytogenetic and molecular genetic evidence suggests that multiple somatic genetic
      events are required for tumorigenic conversion of a mesothelial cell. As with
      many other types of cancer, in MM critical oncogenic events exert their action
      via perturbations of the cell cycle. Interactions between the retinoblastoma (Rb)
      family of proteins and oncoproteins encoded by SV40 lead to cell cycle
      alterations. Likewise, inhibition of the p53 tumor suppressor by SV40 can
      inactivate a crucial cell cycle checkpoint, thereby permitting cells to undergo
      mitosis regardless of the presence of DNA damage. Many MMs exhibit loss and/or
      inactivation of the tumor suppressors p16(INK4a)and p14(ARF), components of the
      pRb and p53 cell cycle regulatory pathways, respectively. Recent investigations
      have demonstrated that SV40 large T antigen, isolated from frozen biopsies of
      human MM specimens, binds to and inactivates various tumor suppressor gene
      products such as pRb and p53. In this review, we discuss how SV40-oncosuppressor
      interactions can lead to functional alterations of the pRb- and p53-dependent
      cell cycle regulatory pathways and thereby contribute to neoplastic
      transformation of human mesothelial cells.

PMID- 11243898
TI  - Simian virus 40 regulatory region structural diversity and the association of
      viral archetypal regulatory regions with human brain tumors.
AB  - The regulatory region (RR) of simian virus 40 (SV40) contains enhancer/promoter
      elements and an origin of DNA replication. Natural SV40 isolates from simian
      brain or kidney tissues typically have an archetypal RR arrangement with a single
      72-basepair enhancer element. A rare simpler, shorter SV40 RR exists that lacks a
      duplicated sequence in the G/C-rich region and is termed protoarchetypal.
      Occasionally, SV40 strain variants arise de novo that have complex RRs, which
      typically contain sequence reiterations, rearrangements, and/or deletions. These
      variants replicate faster and to higher titers in tissue culture; we speculate
      that such faster-growing variants were selected when laboratory strains of SV40
      were initially recovered. SV40 strains with archetypal RRs have been found in
      some human brain tumors. The possible implications of these findings and a brief
      review of the SV40 RR structure are presented.

PMID- 11243899
TI  - Association of SV40 with human tumours.
AB  - SV40 was discovered as a contaminant of poliovirus vaccines that were
      inadvertently administered to millions of people in Europe and the United States
      between 1955 and 1963. Shortly afterwards, SV40 was proven to be oncogenic in
      rodents and capable of transforming human and animal cells in vitro. The
      possibility that SV40 might cause tumours in humans thus became a subject of
      scientific and public interest and scrutiny. However, largely due to a lack of
      significant epidemiological evidence, interest in assessing SV40's potential
      carcinogenic role in humans diminished. Recently, many laboratories have reported
      the presence of SV40-like DNA in a high proportion of human mesotheliomas,
      ependymomas and osteosarcoma (the three main types of tumours caused by virus in
      hamsters), renewing the question whether SV40 might be a human tumour virus.
      Molecular data from these studies are reviewed to re-evaluate the potential role
      of SV40 as a human carcinogen.

PMID- 11243900
TI  - SV40 and the pathogenesis of mesothelioma.
AB  - Malignant mesothelioma, a tumor of the pleura, pericardium, and peritoneum, is
      presently a worldwide problem. Current therapy is ineffective in slowing the
      course of the disease, and median survival from the time of diagnosis is rarely
      greater than 1 year. While the tumor was almost unknown prior to the second half
      of the twentieth century, it is presently responsible for more than 2000 deaths
      per year in the US alone. Mesothelioma is frequently associated with exposure to
      asbestos, but the incidence of cases involving individuals with low levels of
      asbestos exposure is increasing. For this reason, there has been much interest in
      studying whether there are alternative factors that act alone or in conjunction
      with asbestos in producing this malignancy. In the last decade, simian virus 40
      (SV40) has become the most notable suspected agent.

PMID- 11243901
TI  - Strategies to circumvent SV40 oncoprotein expression in malignant pleural
      mesotheliomas.
AB  - Although nearly 60% of mesotheliomas contain SV40 early region DNA sequences, the
      role of T/t antigens in initiating and maintaining the transformed state of
      mesothelioma cells remains unclear. The majority of mesothelioma cells which
      contain SV40 early region sequences exhibit extremely low basal expression of
      SV40 oncoproteins; however, T/t antigen expression can be induced under
      conditions of cellular stress. Abrogation of SV40 T/t expression by antisense
      techniques induces apoptosis in part via restoration of p53 function, and
      enhances chemosensitivity in SV40 (+) MPM cells by mechanisms which have not been
      fully elucidated. This review briefly summarizes our ongoing efforts to define
      the role of SV40 oncoproteins in modulating the malignant phenotype of
      mesothelioma cells, and highlights strategies which may prove efficacious in vivo
      for circumventing SV40 T/t antigen expression in mesotheliomas.

PMID- 11243902
TI  - Prospects for an SV40 vaccine.
AB  - The identification of SV40 as a possible cause of human cancer leads to the
      question of whether the unique properties of the virus can be exploited to treat
      patients with SV40-positive mesotheliomas, which are otherwise refractory to
      successful intervention. A modified SV40 T antigen, from which the transforming
      domains have been removed, has been cloned into a vaccinia virus vector and
      tested in animal tumor model systems. It has been shown to be effective against
      both subsequent tumor challenge and pre-existing tumors. Thus, the potential
      exists for use of such a vaccine in mesothelioma patients.

PMID- 11243903
TI  - The manual therapist as an educator.

PMID- 11243904
TI  - Functional stability re-training: principles and strategies for managing
      mechanical dysfunction.
AB  - Functional stability is dependent on integrated local and global muscle function.
      Mechanical stability dysfunction presents as segmental (articular) and multi
      segmental (myofascial) dysfunction. These dysfunctions present as combinations of
      restriction of normal motion and associated compensations (give) to maintain
      function. Stability dysfunction is diagnosed by the site and direction of give or
      compensation that relates to symptomatic pathology. Strategies to manage
      mechanical stabililty dysfunction require specific mobilization of articular and
      connective tissue restrictions, regaining myofascial extensibility, retraining
      global stability muscle control of myofascial compensations and local stability
      muscle recruitment to control segmental motion. Stability re-training targets
      both the local and global stability systems. Activation of the local stability
      system to increase muscle stiffness along with functional low-load integration in
      the neutral joint position controls segmental or articular give. Global muscle
      retraining is required to correct multisegmental or myofascial dysfunction in
      terms of controlling the site and direction of load that relates to provocation.
      The strategy here is to train low-load recruitment to control and limit motion at
      the site of pathology and then actively move the adjacent restriction, regain
      through range control of motion with the global stability muscles and regain
      sufficient extensibility in the global mobility muscles to allow normal function.
      Individual strategies for integrating local and global recruitment retraining
      back into normal function are suggested.

PMID- 11243905
TI  - Movement and stability dysfunction--contemporary developments.
AB  - A good understanding of the control processes used to maintain stability in
      functional movements is essential for clinicians who attempt to treat or manage
      musculoskeletal pain problems. There is evidence of muscle dysfunction related to
      the control of the movement system. There is a clear link between reduced
      proprioceptive input, altered slow motor unit recruitment and the development of
      chronic pain states. Dysfunction in the global and local muscle systems is
      presented to support the development of a system of classification of muscle
      function and development of dysfunction related to musculoskeletal pain. The
      global muscles control range of movement and alignment, and evidence of
      dysfunction is presented in terms of imbalance in recruitment and length between
      the global stability muscles and the global mobility muscles. Direction related
      restriction and compensation to maintain function is identified and related to
      pathology. The local stability muscles demonstrate evidence of failure of
      adequate segmental control in terms of allowing excessive uncontrolled
      translation or specific loss of cross-sectional area at the site of pathology.
      Motor recruitment deficits present as altered timing and patterns of recruitment.
      The evidence of local and global dysfunction allows the development of an
      integrated model of movement dysfunction.

PMID- 11243906
TI  - Electromyographic fatigue characteristics of the quadriceps in patellofemoral
      pain syndrome.
AB  - This study compared the fatigue characteristics of the vastus medialis oblique
      (VMO), vastus lateralis (VL) and rectus femoris (RF) muscles. Ten healthy
      subjects with 10 patients with patellofemoral pain syndrome (PFPS) performed an
      isometric leg press for 60 seconds at 60% MVIC with data collected using surface
      EMG. The power spectrum was analyzed and the extracted median frequency
      normalised to calculate a linear regression slope for each muscle. A repeated
      measures ANOVA revealed no significant differences, neither between the groups
      (P=0.592) nor the muscles (P=0.434). However, the slopes for the VMO and VL were
      different between the two groups with similar slopes for the RF. There was much
      larger variability of MF values in the PFPS group. The VMO:VL ratio calculated
      from these slopes for the healthy subjects was 1.17 and for the PFPS group was
      1.78. These results may indicate unusual features in the fatigue indices of the
      quadriceps in PFPS.

PMID- 11243907
TI  - Mid-thoracic tenderness: a comparison of pressure pain threshold between spinal
      regions, in asymptomatic subjects.
AB  - Palpation for tenderness forms an important part of the manual therapy assessment
      for musculoskeletal dysfunction. In conjunction with other testing procedures it
      assists in establishing the clinical diagnosis. Tenderness in the thoracic spine
      has been reported in the literature as a clinical feature in musculoskeletal
      conditions where pain and dysfunction are located primarily in the upper
      quadrant. This study aimed to establish whether pressure pain thresholds (PPTs)
      of the mid-thoracic region of asymptomatic subjects were naturally lower than
      those of the cervical and lumbar areas. A within-subject study design was used to
      examine PPT at four spinal levels C6, T4, T6, and L4 in 50 asymptomatic
      volunteers. Results showed significant (P<0.001) regional differences. PPT values
      increased in a caudal direction. The cervical region had the lowest PPT scores,
      that is was the most tender. Values increased in the thoracic region and were
      highest in the lumbar region. This study contributes to the normative data on
      spinal PPT values and demonstrates that mid-thoracic tenderness relative to the
      cervical spine is not a normal finding in asymptomatic subjects.

PMID- 11243908
TI  - Indenter head area and testing frequency effects on posteroanterior lumbar
      stiffness and subjects' rated comfort.
AB  - Although several mechanical devices have been developed to objectively assess
      posteroanterior (PA) stiffness of the lumbar spine, no standardized testing
      protocol has been adopted. Two factors that may vary across protocols, and that
      effect measured stiffness and the comfort of the test subject, are the size of
      the indenter head used to apply the PA pressure, and indenting frequency. Three
      variables; PA stiffness, defined as the slope of the stiffness curve (K), the
      displacement of the indenter at 30N (D30), and rating of perceived comfort, were
      measured in 36 subjects asymptomatic for low back pain. For each subject nine
      tests were conducted, using three different indenter head sizes (300mm(2),
      720mm(2)and 1564mm(2)) at each of three different testing frequencies (0.25 Hz,
      0.5 Hz and 2 Hz). Machine testing with a large indenter head produced a lower K
      value, an increased D30 value and higher perceived comfort, while a fast testing
      frequency produced a higher K value and a lower D30 value. An indenter size by
      frequency interaction showed small indenter heads to be least comfortable at slow
      speed. The differences found suggest that the indenter head size and the testing
      frequency should be standardized during mechanical spinal stiffness testing.

PMID- 11243909
TI  - Exercise induced leg pain in young athletes misdiagnosed as pain of musculo
      skeletal origin.

PMID- 11243912
TI  - Effects of Doxorubicin (Adriamycin) and [(+)-1,2-bis(3,5-dioxopiperazinyl-1
      yl)]propane (ICRF-187) on skeletal muscle protease activities.
AB  - Adverse effects of doxorubicin (adriamycin) have been reported to be due to iron
      catalyzed free radical formation, which can be prevented with the cytoprotective
      chelating agent [(+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)]propane (dexrazoxane;
      ICRF-187). Affected tissues include the heart, gastrointestinal tract, and
      kidney. However, there is very little information on the effects of adriamycin on
      skeletal muscle, despite the fact that there is direct and indirect evidence to
      show that both adriamycin and ICRF-187 are myotoxic. To investigate the
      mechanisms of cytotoxicity of these agents in skeletal muscle, we have conducted
      a systematic investigation of the activities of the major lysosomal (dipeptidyl
      aminopeptidase I and II and cathepsins B, D, H, and L) and cytoplasmic (alanyl-,
      arginyl-, and leucyl aminopeptidase, dipeptidyl aminopeptidase IV, tripeptidyl
      aminopeptidase, and proline endopeptidase) muscle proteases. These enzymes play
      an important role in normal cellular function and represent potential targets for
      toxic and protective agents. Male Wistar rats (approx. 0.2 kg) were subjected to
      a pretreatment phase of 30 min followed by a treatment stage of either 2.5 or 24
      h. The pretreatment involved injection of a single bolus of either saline (0.15
      mol/l NaCl; 5 ml/kg ip) or ICRF-187 (100 mg/kg; 5 ml/kg ip). After 30 min, rats
      were injected again with a single bolus of either adriamycin (5 mg/kg; 10 ml/kg
      ip) or saline (0.15 mol/l NaCl; 10 ml/kg ip) in the treatment phase. At either
      2.5 or 24 h after the last adriamycin or saline injection, rats were killed for
      subsequent dissection of the gastrocnemius muscle for analysis. In the 2.5-h
      study, there were significant reductions in cathepsin D activities of adriamycin
      treated rats compared to saline injected control (p = 0.02). In both 2.5- and 24
      h studies there were also significant differences (p = 0.05) in cathepsin H
      activities between rats treated with adriamycin and ICRF-187, although these
      differences were not significant when data were compared with corresponding
      saline-injected rats. There were no other overt effects for any of the other
      proteases at either 2.5 or 24 h. We conclude that both adriamycin and ICRF-187
      have very little effect on the activities of muscle proteases and that altered
      proteolysis is not involved in the reported pathological reactions induced by
      these agents.

PMID- 11243913
TI  - Butyltin exposure causes a rapid decrease in cyclic AMP levels in human
      lymphocytes.
AB  - Natural killer (NK) cells are a subset of lymphocytes that are capable of killing
      tumor cells, virally infected cells, and antibody-coated cells. Butyltins (BTs)
      are used in a variety of consumer products and industrial applications.
      Tributyltin (TBT) is found in dairy products, meat, and fish. Dibutyltin (DBT) is
      found in plastic products, beverages stored in PVC pipes during manufacturing,
      and poultry products. BTs appear to increase the risk of cancer and viral
      infections in exposed individuals. This increased risk may be due in part to the
      inhibitory effect of these compounds on the cytotoxic function of NK cells. A 24
      h exposure of NK cells to 200 nM TBT or 1.5 microM DBT decreased the cytotoxic
      function of NK cells by greater than 90%. Higher concentrations of TBT and DBT
      decreased the cytotoxic function of NK cells (by greater than 90%) after only a 1
      h exposure. A 24-h exposure to either TBT or DBT decreased intracellular ATP
      levels by about 30%. However, as much as a 1-h exposure to either 300 nM TBT or
      10 microM DBT caused no significant decrease in ATP levels. Thus, a decrease in
      ATP levels is a longer-term consequence of BT exposure. Intracellular levels of
      cAMP are decreased by as much as 80% within 5 min of exposure to either TBT or
      DBT. This rapid decline in cAMP levels in NK cells may be a consequence of BT
      exposure that is related to the rapid decrease in the cytotoxic function of NK
      cells.

PMID- 11243914
TI  - Disruption of mitochondrial respiration by melatonin in MCF-7 cells.
AB  - Clinical and laboratory studies have provided evidence of oncostatic activity by
      the pineal neurohormone melatonin. However, these studies have not elucidated its
      mechanism of action. The following series of MCF-7 breast tumor cell studies
      conducted in the absence of exogenous steroid hormones provide evidence for a
      novel mechanism of oncostatic activity by this endogenous hormone. We observed a
      40--60% loss of MCF-7 cells after 20-h treatment with 100 nM melatonin, which
      confirmed and extended previous reports of its oncostatic potency. Interestingly,
      there were no observed changes in tritiated thymidine uptake, suggesting a lack
      of effect on cell cycle/nascent DNA synthesis. Further evidence of a cytocidal
      effect came from morphologic observations of acute cell death and
      autophagocytosis accompanied by degenerative changes in mitochondria. Studies of
      mitochondrial function via standard polarography revealed a significant increase
      in oxygen consumption in melatonin-treated MCF-7 cells. Enzyme-substrate studies
      of electron transport chain (complex IV) activity in detergent permeabilized
      cells demonstrated a concomitant 53% increase (p < 0.01) in cytochrome c oxidase
      activity. Additional studies of succinate dehydrogenase activity (complex II) as
      determined by reduction of (3-4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium
      bromide demonstrated a significant increase (p < 0.05) in melatonin-treated cells
      and further confirmed the accelerated ET activity. Finally, there was a 64%
      decrease (p < 0.05) in cellular ATP levels in melatonin-treated cells. The G
      protein-coupled melatonin receptor antagonist luzindole abrogated the cytotoxic
      and mitochondrial effects. These studies suggest a receptor-modulated pathway of
      cytotoxicity in melatonin-treated MCF-7 tumor cells with apparent uncoupling of
      oxidative phosphorylation.

PMID- 11243915
TI  - Aryl hydrocarbon receptor-deficient mice generate normal immune responses to
      model antigens and are resistant to TCDD-induced immune suppression.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
      that mediates many of the toxic effects induced by exposure to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), a high-affinity AhR ligand and a potent
      immunotoxicant. AhR-deficient mice have been constructed, and there are reports
      that the animals display altered splenic architecture and cellularity with an
      apparent increased incidence of infection. These observations have led to
      speculation that the immune system of these animals might be compromised,
      however, their functional immune response has not been directly tested. In the
      studies presented here, we examined the immune response of two strains of 8- to
      10-week-old AhR-deficient mice. Mice were challenged with model antigens,
      allogeneic P815 tumor cells, or sheep red blood cells, and their ability to
      generate cell-mediated and humoral immune responses was examined. In addition, to
      address the obligatory role of the AhR in TCDD-induced immune suppression, we
      examined the immune response of the AhR-null animals following exposure to an
      immunosuppressive dose of TCDD. Results from these studies showed that AhR
      deficient mice were able to mount normal productive immune responses to both
      model antigens and that neither the cellular nor the humoral response was
      suppressed by exposure to TCDD. Interestingly, however, we found that the immune
      response of heterozygous AhR(+/-) mice was less sensitive to TCDD than homozygous
      AhR(+/+) mice. The results of these studies suggest that the absence of the AhR
      does not impact the function of the immune system, but confirm the findings of
      previous studies that have indicated the AhR plays an obligatory role in TCDD
      induced immune suppression.

PMID- 11243916
TI  - Reactive oxygen species and substance P in monocrotaline-induced pulmonary
      hypertension.
AB  - We attempted to evaluate whether the antioxidants 1,3-dimethyl-2-thiourea (DMTU)
      and hexa(sulfobutyl)fullerenes (FC(4)S) attenuate monocrotaline (MCT)-induced
      pulmonary hypertension (PH) by lowering lung substance P (SP) in Wistar rats.
      Sixty-three rats weighing 297 +/- 8 g were divided into six groups: control; MCT;
      capsaicin + MCT; MCT + DMTU-1; MCT + DMTU-2; and MCT + FC(4)S. Three weeks before
      the functional study, saline was injected into each control rat, whereas each MCT
      rat received 60 mg/kg sc MCT. Rats in the third group received capsaicin
      pretreatment followed by MCT. A 3-day injection of DMTU was performed during the
      early (DMTU-1) or the late (DMTU-2) post-MCT period. For the last group, each MCT
      treated rat received a daily FC(4)S injection until the commencement of the
      functional study. Compared to the control group, MCT caused significant increases
      in pulmonary arterial pressure (Ppa), right ventricular hypertropy, pulmonary
      arterial medial thickness, lung SP level, and luminol-enhanced chemiluminescence
      counts in bronchoalveolar lavage. Both capsaicin and antioxidants significantly
      attenuated the above MCT-induced alterations. SP-induced acute increase in Ppa
      was exaggerated in MCT-treated rats. These results suggest that oxygen radicals
      play an important role in MCT-induced PH via elevating lung SP level.

PMID- 11243917
TI  - The determination of draining lymph node cell cytokine mRNA levels in BALB/c mice
      following dermal sodium lauryl sulfate, dinitrofluorobenzene, and toluene
      diisocyanate exposure.
AB  - Differential modulation has been demonstrated in interleukin-4 (IL-4), IL-10, and
      interferon gamma (IFN-gamma) mRNA and protein secretion patterns of cells
      isolated from the draining lymph nodes of mice following exposure to T cell and
      respiratory sensitizers. Using a multiprobe ribonuclease protection assay, the
      following investigation examined the mRNA expression patterns of multiple
      cytokines associated with respiratory sensitization for modulation following
      exposure to chemicals known primarily to induce irritation (sodium lauryl
      sulfate), respiratory sensitization (toluene diisocyanate), or T cell-mediated
      hypersensitivity (dinitrofluorobenzene) responses. On days 0 and +5 female BALB/c
      mice were exposed to either test article or vehicle on the shaven dorsal lumbar
      region; on days +10 through +12 the mice received test article on the dorsal
      aspect of each ear. On day +13 animals were euthanized, draining lymph nodes were
      excised, and mRNA was isolated immediately or following 24 or 48 h of culture in
      the presence or absence of concanavalin (Con) A. Differential expression of
      cytokine mRNA was most notable following 24 h incubation with Con A. Modulation
      of IL-4, -10, and IFN-gamma following chemical exposure was consistent with
      previous studies. In addition, IL-9, -13, and -15 were significantly elevated
      only following toluene diisocyanate exposure. Further investigations of these
      cytokines may provide additional insight into the mechanisms of chemically
      induced respiratory sensitization and provide endpoints for the detection of a
      chemical's ability to elicit IgE-mediated hypersensitivity responses.

PMID- 11243921
TI  - William D. Hamilton's work in evolutionary game theory.

PMID- 11243918
TI  - The role of methyl-linoleic acid epoxide and diol metabolites in the amplified
      toxicity of linoleic acid and polychlorinated biphenyls to vascular endothelial
      cells.
AB  - Selected dietary lipids may increase the atherogenic effects of environmental
      chemicals, such as polychlorinated biphenyls (PCBs), by cross-amplifying
      mechanisms leading to dysfunction of the vascular endothelium. We have shown
      previously that the omega-6 parent fatty acid, linoleic acid, or 3,3',4,4'
      tetrachlorobiphenyl (PCB 77), an aryl hydrocarbon (Ah) receptor agonist,
      independently can cause disruption of endothelial barrier function. Furthermore,
      cellular enrichment with linoleic acid can amplify PCB-induced endothelial cell
      dysfunction. We hypothesize that the amplified toxicity of linoleic acid and PCBs
      to endothelial cells could be mediated in part by cytotoxic epoxide metabolites
      of linoleic acid called leukotoxins (LTX) or their diol derivatives (LTXD).
      Exposure to LTXD resulted in a dose-dependent increase in albumin transfer across
      endothelial cell monolayers, whereas this disruption of endothelial barrier
      function was observed only at a high concentration of LTX. Pretreatment with the
      cytosolic epoxide hydrolase inhibitor 1-cyclohexyl-3-dodecyl urea partially
      protected against the observed LTX-induced endothelial dysfunction. Endothelial
      cell activation mediated by LTX and/or LTXD also enhanced nuclear translocation
      of the transcription factor NF-kappa B and gene expression of the inflammatory
      cytokine IL-6. Inhibiting cytosolic epoxide hydrolase decreased the LTX-mediated
      induction of both NF-kappa B and the IL-6 gene, whereas the antioxidant vitamin E
      did not block LTX-induced endothelial cell activation. Most importantly,
      inhibition of cytosolic epoxide hydrolase blocked both linoleic acid-induced
      cytotoxicity, as well as the additive toxicity of linoleic acid plus PCB 77 to
      endothelial cells. Interestingly, cellular uptake and accumulation of linoleic
      acid was markedly enhanced in the presence of PCB 77. These data suggest that
      cytotoxic epoxide metabolites of linoleic acid play a critical role in linoleic
      acid-induced endothelial cell dysfunction. Furthermore, the severe toxicity of
      PCBs in the presence of linoleic acid may be due in part to the generation of
      epoxide and diol metabolites. These findings have implications in understanding
      interactive mechanisms of how dietary fats can modulate dysfunction of the
      vascular endothelium mediated by certain environmental contaminants.

PMID- 11243922
TI  - William D. Hamilton: a tribute.

PMID- 11243923
TI  - Biological information, kin selection, and evolutionary transitions.

PMID- 11243924
TI  - Individual selection and altruistic relationships: the legacy of W. D. Hamilton.

PMID- 11243925
TI  - W. D. Hamilton-evolutionary theorist: life and vision (1936-2000).

PMID- 11243926
TI  - Phylogenetic inferences from molecular sequences: review and critique.
AB  - Conflicting results often accompany phylogenetic analyses of RNA, DNA, or protein
      sequences across diverse species. Causes contributing to these conflicts relate
      to ambiguities in identifying homologous characters of alignments, sensitivity of
      tree-making methods to unequal evolutionary rates, biases in species sampling,
      unrecognized paralogy, functional differentiation, loss of phylogenetic
      informational content due to long branches or fast evolution, and difficulties
      with the assumptions and approximations used to infer phylogenetic relationships.
      Attempts to surmount these conflicts by averaging over many proteins are
      problematic due to inherent biases of selected families, lack of signal in
      others, and events of lateral transfer, fusion, and/or chimerism. The process of
      assessing reliability of the results using the bootstrap method is strewn with
      obstacles because of lack of independence and inhomogeneity in the molecular
      data. Problems inherent to the three major procedures for developing phylogenetic
      trees--parsimony, likelihood, distance--are reviewed. Special attention is given
      to the problem of inferring evolutionary distances from patterns of similarity
      among sequences. The difficulties encountered by methods of phylogenetic
      reconstructions based on the analysis of divergent sequence families make new
      methods based on the analysis of complete genomes reasonable alternatives.
      Several of these are considered, including the signature sequences of Gupta and
      associates, the study of genome profiles, and the genomic signature set forth by
      Karlin and colleagues.

PMID- 11243927
TI  - Improved inference of mutation rates: I. An integral representation for the Luria
      Delbruck distribution.
AB  - The estimation of mutation rates is ordinarily performed using results based on
      the Luria-Delbruck distribution. There are certain difficulties associated with
      the use of this distribution in practice, some of which we address in this paper
      (others in the companion paper, Oprea and Kepler, Theor. Popul. Biol., 2001). The
      distribution is difficult to compute exactly, especially for large values of the
      random variable. To overcome this problem, we derive an integral representation
      of the Luria-Delbruck distribution that can be computed easily for large culture
      sizes. In addition, we introduce the usual assumption of very small probability
      of having a large proportion of mutants only after the generating function has
      been computed. Thus, we obtain information on the moments for the more general
      case. We examine the asymptotic behavior of this system. We find a scaling or
      "standardization" technique that reduces the family of distributions
      parameterized by three parameters (mutation rate, initial cell number, and final
      cell number) to a single distribution with no parameters, valid so long as the
      product of the mutation rate and the final culture is sufficiently large. We
      provide a pair of techniques for computing confidence intervals for the mutation
      rate. In the second paper of this series, we use the distribution derived here to
      find approximate distributions for the case where the cell cycle time is not well
      described as an exponential random variable as is implicitly assumed by Luria
      Delbruck distribution.

PMID- 11243928
TI  - Improved inference of mutation rates: II. Generalization of the Luria-Delbruck
      distribution for realistic cell-cycle time distributions.
AB  - In the first paper of this series (Kepler and Oprea, Theor. Popul. Biol. 2001) we
      found a continuum approximation of the Luria-Delbruck distribution in terms of a
      scaled variable related to the proportion of mutants in the culture. Here we show
      that the Luria-Delbruck distribution is inaccurate when realistic division
      processes are being considered due to the non-Markovian character of the cell
      cycle. We derive the expectation of the proportion of mutants in the culture for
      arbitrary cell-cycle time distributions. We then introduce a two-parameter
      generalization of the continuum Luria-Delbruck distribution for two of the more
      commonly used cell-cycle time distributions: gamma and shifted exponential. We
      obtain the generalized distribution by defining a map from the actual parameters
      to "effective" parameters. The effective mutation rate is obtained analytically,
      while the effective population size is obtained by fitting simulation data. Our
      simulations show that the second parameter depend mostly on the coefficient of
      variation of the cell-cycle time distribution.

PMID- 11243929
TI  - Modeling genetic architecture: a multilinear theory of gene interaction.
AB  - The map from genotype to phenotype is an exceedingly complex function of central
      importance in biology. In this work we derive and analyze a mathematically
      tractable model of the genotype-phenotype map that allows for any order of gene
      interaction. By assuming that the alterations of the effect of a gene
      substitution due to changes in the genetic background can be described as a
      linear transformation, we show that the genotype-phenotype map is a sum of linear
      and multilinear terms of operationally defined "reference" effects at each locus.
      The "multilinear" model is used to study the effect of epistasis on quantitative
      genetic variation, on the response to selection, and on genetic canalization. It
      is shown how the model can be used to estimate the strength of "functional"
      epistasis from a variety of genetic experiments.

PMID- 11243930
TI  - Calibration of the calcium dissociation constant of Rhod(2)in the perfused mouse
      heart using manganese quenching.
AB  - Both theoretical and experimental results are presented for in vivo calibration
      of the dissociation constant K(Ca)(d)of the calcium-sensitive fluorescent dye
      Rhod(2)in the perfused mouse heart, using manganese quenching of fluorescence
      transients. An analytical model is derived, based on the biochemical equilibrium
      of manganese competition with calcium for Rhod(2)binding. Expressing the
      differential of the changes between systole and diastole in fluorescence
      transient (delta Delta F(sys-dia)). delta DeltaF(sys-dia)in a beating heart as a
      function of the perfusate manganese concentration [Mn(2+)](p)allows correlation
      of the measured differential transient changes delta Delta F(sys-dia)with the
      calcium dissociation constant K(Ca)(d)of Rhod(2)and the calcium concentration in
      the heart. Numerical modeling indicates that the K(Ca)(d)predominantly affects
      the asymptotic slope of the delta Delta F(sys-dia)versus [Mn(2+)](p)curve at
      certain manganese concentrations, which suggests that the K(Ca)(d)can be
      inversely calculated by partially fitting the delta Delta F(sys-dia)distribution
      as a function of the perfusate manganese concentration. The feasibility of this
      approach is confirmed by quenching of calcium transients by manganese infusion
      into isolated perfused beating mouse hearts. The resulting calculated
      dissociation constant K(Ca)(d)of Rhod(2)is 720nM. Using the same approach, we are
      able to also estimate intracellular calcium concentrations of 700nM at peak
      systole and 300nM in diastole. This is in good agreement with values obtained by
      calibration of fluorescence values with a calcium saturation tetanization
      procedure in the same perfused mouse heart model.

PMID- 11243931
TI  - Calcium requirement for efficient phagocytosis by Dictyostelium discoideum.
AB  - Extracellular EDTA suppressed in a dose-dependent manner the phagocytosis of
      yeast particles by Dictyostelium discoideum cells. Activity was restored fully by
      the addition of Ca(2+), and partially by the addition of Mn(2+)or Zn(2+), but
      Mg(2+)was ineffective. The pH-sensitive, Ca(2+)-specific chelator EGTA also
      inhibited phagocytosis at pH 7.5, but not at pH 5, and Ca(2+)restored the
      inhibited phagocytosis. In contrast, pinocytosis was unaffected by EDTA.
      Consistent with the idea that Ca(2+)was required for phagocytosis, D. discoideum
      growth on bacteria was inhibited by EDTA, which was then restored by the addition
      of Ca(2+). It is concluded that Ca(2+)was needed for efficient phagocytosis by D.
      discoideum amoebae. A search for Ca(2+)-dependent membrane proteins enriched in
      phagosomes revealed the presence of p24, a Ca(2+)-dependent cell-cell adhesion
      molecule-1 (DdCAD-1) that could be the target of the observed EDTA and EGTA
      inhibition. DdCAD-1-minus cells, however, had normal phagocytic activity.
      Furthermore, phagocytosis was inhibited by EDTA and rescued by Ca(2+)in the
      mutant just as in wild type. Thus, DdCAD-1 was not responsible for the observed
      Ca(2+)-dependence of phagocytosis, indicating that one or more different Ca(2+)
      dependent molecule(s) was involved in the process.

PMID- 11243932
TI  - Mechanism by which wortmannin and LY294002 inhibit catecholamine secretion in the
      rat adrenal medullary cells.
AB  - The effects of wortmannin and LY294002, inhibitors of PI(3)-kinase, in
      secretagogue-stimulated rat adrenal chromaffin cells loaded with Calcium Green-1
      were studied by simultaneously measuring changes in the fluorescence intensity of
      the indicator (Ca-response) and in the release of catecholamine (secretory
      response). Before application of these agents, the profile of the secretory
      response evoked by a 10-min stimulation with 30 mM K(+)] was approximated by the
      k th (2.6 on average) power of that of the Ca-response. Both agents dose
      dependently inhibited the high-K(+)-elicited Ca-response and secretory response
      in a similar mode to which the k th power relation was preserved despite the
      occurrence of profound changes in the shapes and sizes of these two responses.
      The L-type Ca(2+)-channel blocker PN200-110 inhibited the high-K(+)-evoked
      responses in a similar fashion. Thus, it is likely that wortmannin and LY294002
      inhibit high-K(+)-evoked CA secretion by inhibiting a Ca(2+)-influx through
      voltage-dependent Ca(2+)channels. Although regulation of L-type Ca(2+)channel
      activity via PI(3)-kinase has been reported in vascular myocytes, this
      possibility may be limited in the present case since the doses of LY294002 and
      wortmannin used to inhibit the secretory response are much higher than IC(50)'s
      for inhibition of PI(3)-kinase with these agents. Compared with the high-K(+)
      elicited responses, muscarine-evoked Ca-responses and secretory responses were
      more strongly inhibited by wortmannin, but less affected by LY294002. The
      differential effects suggest that the inhibition of the muscarine-evoked
      secretion by these agents i s not associated with the inhibition of PI(3)-kinase.

PMID- 11243933
TI  - Sorting of calcium signals at the junctions of endoplasmic reticulum and
      mitochondria.
AB  - Calcium signal transmission between endoplasmic reticulum (ER) and mitochondria
      is supported by a local [Ca(2+)] control that operates between IP(3)receptor
      Ca(2+)release channels (IP(3)R) and mitochondrial Ca(2+)uptake sites, and
      displays functional similarities to synaptic transmission. Activation of IP(3)R
      by IP(3)is known to evoke quantal Ca(2+)mobilization that is associated with
      incremental elevations of mitochondrial matrix [Ca(2+)] ([Ca(2+)](m)). Here we
      report that activation of IP(3)R by adenophostin-A (AP) yields non-quantal
      Ca(2+)mobilization in mast cells. We also show that the AP-induced continuous
      Ca(2+)release causes relatively small [Ca(2+)](m)responses, in particular, the
      sustained phase of Ca(2+)release is not sensed by the mitochondria. Inhibition of
      ER Ca(2+)pumps by thapsigargin slightly increases IP(3)-induced
      [Ca(2+)](m)responses, but augments AP-induced [Ca(2+)](m)responses in a large
      extent. In adherent permeabilized cells exposed to elevated [Ca(2+)], ER
      Ca(2+)uptake fails to affect global cytosolic [Ca(2+)], but attenuates
      [Ca(2+)](m)responses. Moreover, almost every mitochondrion exhibits a region very
      close to ER Ca(2+)pumps visualized by BODIPY-FL-thapsigargin or SERCA antibody.
      Thus, at the ER-mitochondrial junctions, localized ER Ca(2+)uptake provides a
      mechanism to attenuate the mitochondrial response during continuous Ca(2+)release
      through the IP(3)R or during gradual Ca(2+)influx to the junction between ER and
      mitochondria.

PMID- 11243934
TI  - Kinetics of activation of a PKC-regulated epithelial calcium channel.
AB  - The kinetics of calcium entry through regulated calcium channels in cultured
      renal proximal tubule cells was studied with Fura-2 fluorescence ratio imaging in
      single cells. The calcium entry was activated by 1-oleoyl-2-acetyl-sn-glycerol
      (OAG) and phorbol-12-myristat-13-acetate (PMA), similar to that observed for
      activation by osmo-mechanical stress. OAG (2.5 microM) or PMA (0.5 microM)
      activated calcium entry is characterized by a significant latency between agonist
      application and the response, whereas the effect of osmo-mechanical stress was
      immediate. This pre-response latency was 260 +/- 70s with OAG stimulation and
      79.2 +/- 17.3s with PMA stimulation. Once a cell responds, the intracellular
      calcium level reaches a peak value within seconds. The cell response to agonist
      is independent of the response of neighboring cells. The response kinetics
      resembles those of the calcium sparks in excitable cells, except the response is
      much slower. In all cases, the response appears to be an all-or-none event, that
      is characteristics of an elementary binary switch. It is suggested that the
      binary response and the lack of coordinated response of calcium entry in single
      cells results from limited availability of the calcium channels and/or PKC that
      activates the channel. The experimental data could be fit to a single binary
      response mathematical model assuming each response reflected an elementary event
      of a single channel opening or a co-ordinated opening of a cluster of several
      channels.

PMID- 11243935
TI  - Calcium buffering and protection from excitotoxic cell death by exogenous
      calbindin-D28k in HEK 293 cells.
AB  - Calbindin-D28k (CaBP) is a calcium-binding protein found in specific neuronal
      populations in the mammalian brain that, as a result of its proposed calcium
      buffering action, may protect neurons against potentially harmful increases in
      intracellular calcium. We have stably transfected HEK 293 cells with recombinant
      human CaBP in order to determine the influence of this protein upon transient
      increases in intracellular ionic calcium concentration ([Ca(2+)](i)) induced
      either by transient transfection of the NR1 and NR2A subunits of the N-methyl-D
      aspartate (NMDA) receptor and brief exposure to glutamate, photolysis of the
      caged calcium compound NP-EGTA, or exposure to the Ca(2+)]-ionophore 4-Br-A23187.
      The presence of CaBP did not significantly reduce the peak [Ca(2+)](i)stimulated
      by glutamate activation of NMDA receptors but significantly prolonged the
      recovery to baseline values. Flash photolysis of NP-EGTA in control cells
      resulted in an almost instantaneous increase in [Ca(2+)](i)followed by a bi
      exponential recovery to baseline values. In cells stably expressing CaBP, the
      peak [Ca(2+)](i)levels were not statistically different from the controls,
      however, there was a significant prolongation of the initial portion of the slow
      recovery phase. In cells exposed to 4-Br-A23187, the presence of CaBP
      significantly reduced the rate of rise of [Ca(2+)](i), reduced the peak response,
      slowed the rate of recovery, and reduced the depolarization of mitochondria. In
      studies of delayed, Ca(2+)]-dependent cell death, CaBP transfected cells
      exhibited enhanced survival 24h after a 1-h exposure to 200 microM NMDA. However,
      necrotic cell death observed after the first 6h was not prevented by the presence
      of CaBP. These results provide direct evidence for a Ca(2+)-buffering effect of
      CaBP which serves to limit Ca(2+)entry and the depolarization of mitochondria,
      thereby protecting cells from death mediated most likely by apoptosis.

PMID- 11243937
TI  - Steroids for acute exacerbations of COPD : how long is enough?

PMID- 11243938
TI  - alpha(1)-antitrypsin deficiency therapy : pieces of the puzzle.

PMID- 11243939
TI  - Tumor necrosis factor polymorphism in sarcoidosis.

PMID- 11243940
TI  - Endoluminal metastases of the tracheobronchial tree : is there any way out?

PMID- 11243941
TI  - Tuberculosis in correctional facilities : a nightmare without end in sight.

PMID- 11243942
TI  - Should patients with neuromuscular disease be denied the choice of the treatment
      of mechanical ventilation?

PMID- 11243943
TI  - Relationship between bronchial hyperresponsiveness and development of asthma in
      wheezy infants.
AB  - STUDY OBJECTIVES: To evaluate the relationship between bronchial
      hyperresponsiveness (BHR) in infants with wheezing and the subsequent development
      of asthma. INTERVENTION: Bronchial reactivity to inhaled methacholine (BRm)
      during the infantile period was studied using the transcutaneous partial pressure
      of oxygen (tcPO(2)) method. Children were followed long-term for the development
      of asthma. PATIENTS: Fourteen children with bronchiolitis (mean age, 0.7 years)
      and 48 with wheezy bronchitis (mean age, 2.3 years) were enrolled. For
      comparison, 40 children with asthma (mean age, 4.6 years) and 27 healthy control
      subjects without chronic respiratory disease (mean age, 2.7 years) were studied.
      MEASUREMENTS: Consecutive doses of methacholine were doubled until a 10% decrease
      in tcPO(2) from baseline was reached. The cumulative dose of methacholine (Dmin)
      at the inflection point of tcPO(2) (Dmin-PO(2)) was recorded. RESULTS: During >
      10 years of follow-up, seven patients with bronchiolitis developed asthma and all
      patients in the higher BRm set developed asthma, compared with none in the lower
      BRm set. In the wheezy bronchitis group, Dmin-PO(2) values in the 32 patients who
      developed asthma were lower than those in patients who had not developed asthma
      (p < 0.001). CONCLUSIONS: We concluded that there is a tendency for infants with
      a clinical diagnosis of bronchiolitis or wheezy bronchitis and who show BHR in
      the infantile period to develop asthma. The presence of increased BHR after
      infantile respiratory diseases associated with wheezing may be a prelude to the
      development of childhood asthma.

PMID- 11243944
TI  - Association of airway responsiveness with asthma and persistent wheeze in a
      Chinese population.
AB  - STUDY OBJECTIVES: Data from a cross-sectional study were analyzed to examine the
      association of increased airway responsiveness with physician-diagnosed asthma
      and persistent wheeze. DESIGN: Two methods for calculating the provocative dose
      that decreases the airflow rate by 20% (PD(20)) were used as indexes for
      increased airway responsiveness: (1) a 20% drop in FEV(1) calculated from
      baseline FEV(1) (PD(20)b), and (2) a 20% drop in FEV(1) from FEV(1) measurements
      after inhalation of saline solution (PD(20)s). Both PD(20)b and PD(20)s were
      measured through induction by varying doses of methacholine. SETTING: Anqing,
      Anhui Province, China. PARTICIPANTS: Study subjects were 8 to 74 years of age and
      were classified into four groups: children (< 15 years old), young adults (15 to
      29 years old), adults (30 to 44 years old), and older adults (> or 5 years old).
      INTERVENTIONS: The differences in estimated odds ratios of airway
      hyperresponsiveness with asthma and wheeze, sensitivity and specificity, and
      coefficients of variation were compared between PD(20)b and PD(20)s. The sample
      for analysis consisted of 10,284 subjects from 2,663 nuclear families with
      complete data on wheeze, asthma, and major potential confounding factors.
      MEASUREMENTS AND RESULTS: The prevalence of asthma in this sample was lowest in
      subjects with no demonstrable PD(20) and had a reverse dose-response relationship
      with PD(20) across all age groups. Using the receiver operating characteristic,
      the sensitivity and specificity of the PD(20)s or PD(20)b were found to be almost
      identical. A similar trend was found for persistent wheeze, although the
      estimated odds ratios for persistent wheeze appeared slightly smaller than those
      for physician-diagnosed asthma. CONCLUSIONS: This study demonstrates a dose
      response relationship between increased airway responsiveness and asthma and
      wheeze in this Chinese population. PD(20)s or PD(20)b yielded virtually
      indistinguishable results, which indicated that either of the two tests could
      serve as an index of airway hyperresponsiveness.

PMID- 11243945
TI  - Methacholine challenge testing in Reserve Officer Training Corps cadets.
AB  - STUDY OBJECTIVE: To determine the prevalence of positive results for methacholine
      challenge tests in asymptomatic Reserve Officer Training Corps (ROTC) cadets with
      no history of asthma. DESIGN: Prospective, blinded cohort comparison study.
      SETTING: Pulmonary diseases clinic in a US Army tertiary-care medical center.
      PATIENTS: One hundred three college students who were undergoing a physical
      examination before entering active duty. Group 1 subjects, 58 men and 5 women
      with an average age of 22.7 years, had no symptoms or personal history of asthma.
      Group 2 patients, 34 men and 6 women with an average age of 22.2 years, had a
      history or recent suggestive symptoms of asthma. INTERVENTIONS: Methacholine
      challenge testing using concentrations of 0.025, 0.25, 2.5, 10, and 25 mg/mL for
      a total dose of 188 inhalation units or until FEV(1) had declined by 20%.
      RESULTS: Group 2 had significantly more patients with positive results for
      methacholine challenge tests or reversible airflow obstruction at baseline (23 of
      40 patients [57.5%]) than group 1 (8 of 63 patients [12.7%]; p < 0.05). The
      cadets in group 1 with positive results for methacholine challenge tests reacted
      with a 20% decline in FEV(1) at the following concentrations: 25 mg/mL (188 IU),
      2 patients; 10 mg/mL (64 IU), 4 patients; and 2.5 mg/mL (13.8 IU), 2 patients.
      Using values calculated for the provocative concentration of a substance causing
      a 20% fall in FEV(1) and the new American Thoracic Society criteria, four
      patients would have borderline bronchial hyperresponsiveness (4 to 16 mg/mL) and
      three patients (4.8%) would have mild bronchial hyperresponsiveness (1 to 4
      mg/mL). CONCLUSIONS: Asymptomatic US Army ROTC cadets with no history of asthma
      have possible false-positive responses to methacholine at concentrations > 0.25
      mg/mL.

PMID- 11243946
TI  - Asthma and the risk of hospitalization in Canada : the role of socioeconomic and
      demographic factors.
AB  - OBJECTIVE: Asthma is an important determinant of hospitalization. The study aims
      to examine the modifying effects of demographic and socioeconomic factors on the
      relationship between asthma and the overall number of hospitalizations. METHODS:
      We examined the data on 17,601 Canadians who were > or = 12 years of age to
      explore the combined effects of asthma and other factors on hospitalization
      within the context of a publicly funded health-care system. Asthma was determined
      by an affirmative response to the question: "Do you have asthma diagnosed by a
      health professional?" The subjects also were asked whether they had been an
      overnight patient in a hospital during the past 12 months. RESULTS: Asthma as a
      risk factor explained 3.7% of all hospitalizations of men and 2.4% of all
      hospitalizations of women. Overall, hospitalization was positively associated
      with female gender, old age, and low household income. The odds ratio for asthma
      as a risk factor for overall hospitalization (ie, hospitalization for any reason
      and all causes, not only for asthma) was greater for younger men than for older
      men, for less-educated women than for well-educated women, and for men with
      middle or high incomes than for men with low incomes. CONCLUSIONS: These results
      suggest that demographic and socioeconomic factors play a role in the
      relationship between asthma and the overall number of hospitalizations, with
      certain population subgroups being at greater risk of hospitalization in relation
      to asthma.

PMID- 11243947
TI  - Effectiveness and safety of salmeterol in nonspecialist practice settings.
AB  - STUDY OBJECTIVES: To evaluate the effectiveness and safety of inhaled salmeterol
      in patients managed in nonspecialist practice settings. DESIGN: A randomized,
      double-blind, 6-month, parallel-group study involving 253 centers. SETTING:
      Primarily nonspecialist practices (n = 232). PATIENTS: A total of 911 subjects
      (417 men; 494 women) who met American Thoracic Society asthma criteria were
      enrolled and randomized to treatment with either twice-daily salmeterol aerosol
      (50 microg; n = 455) or matching placebo twice daily (n = 456). Both groups were
      allowed to take salbutamol as needed. All subjects were previously treated with
      anti-inflammatory maintenance therapy that was continued throughout the study.
      MEASUREMENTS AND RESULTS: The primary outcome variable was the proportion of
      subjects with serious asthma exacerbations defined as an exacerbation requiring
      hospitalization, emergency department visit, or use of prednisone during the
      treatment period. A total of 712 subjects competed the study. There was no
      significant difference in the proportion of subjects experiencing serious
      exacerbations between the salmeterol and placebo groups (20.8% vs 20.9%,
      respectively; p = 0.935; power > 88%). Peak expiratory flow was significantly
      higher in the salmeterol group (398 L/min vs 386 L/min for placebo; p < 0.01).
      Median daily use of salbutamol was two inhalations for the salmeterol group and
      three inhalations for placebo (p < 0.001). The proportion of subjects sleeping
      through the night was significantly higher in the salmeterol group (74%) as
      compared to placebo (68%; p = 0.028). CONCLUSIONS: Salmeterol treatment is
      effective in subjects typically cared for in the primary-care setting and does
      not increase the frequency of severe exacerbations.

PMID- 11243948
TI  - Underuse of inhaled steroid therapy in elderly patients with asthma.
AB  - STUDY OBJECTIVES: Despite their proven efficacy, inhaled steroids may be
      underused in the elderly asthmatic population. The objectives of this study were
      to determine if inhaled steroids are underused in the elderly asthmatic
      population, who are at a high risk for rehospitalization and mortality, and to
      identify certain risk factors that predict lower use of inhaled steroids in this
      group of patients. DESIGN: Population-based, retrospective, cohort study using
      linked data from hospital discharge and outpatient drug databases. PARTICIPANTS:
      All people > or = 65 years old in Ontario, Canada, who survived an acute
      exacerbation of asthma between April 1992 and March 1997. MEASUREMENTS AND
      RESULTS: Of the 6,254 patients, 2,495 patients (40%) did not receive inhaled
      steroid therapy within 90 days of discharge from their initial hospitalization
      for asthma. Patients > 80 years old were at a greater risk of not receiving
      inhaled steroid therapy, compared to those 65 to 70 years of age (adjusted odds
      ratio [OR], 1.23; 95% confidence interval [CI], 1.05 to 1.47). Patients with a
      Charlson comorbidity index of > or = 3 were also at an increased risk of not
      receiving inhaled steroid therapy, compared to those having no comorbidities
      (adjusted OR, 3.45; 95% CI, 1.56 to 7.69). Moreover, receipt of care from a
      primary-care physician was independently associated with an elevated risk of not
      receiving inhaled steroid therapy, compared to receipt of care from
      respirologists/allergists (adjusted OR, 1.35; 95% CI, 1.10 to 1.61).
      INTERPRETATION: Forty percent of Ontario patients > or = 65 years old who
      experienced a recent acute exacerbation of asthma did not receive inhaled steroid
      therapy near discharge from their initial hospitalization for asthma. Nonreceipt
      of inhaled steroid therapy was particularly prominent in the older patients with
      multiple comorbidities. Moreover, those who received care from primary-care
      physicians were also less likely to receive inhaled steroid therapy, compared to
      those who received care from specialists.

PMID- 11243949
TI  - Systemic glucocorticoids in severe exacerbations of COPD.
AB  - OBJECTIVE: This study aimed to compare the efficacies of 3-day and 10-day courses
      of methylprednisolone (MP) treatment in severe COPD exacerbations necessitating
      hospitalization for respiratory failure. DESIGN: Prospective, randomized, single
      blind study. SETTING: Tertiary-care center. PATIENTS AND METHODS: Thirty-six
      patients were included in the study and randomized into two groups: group 1
      received MP, 0.5 mg/kg q6h for 3 days, and group 2 was administered the same
      dosage of MP for the first 3 days, after which it was tapered and terminated on
      the tenth day. There was no difference between the groups for age, baseline
      FEV(1), PaO(2), PaCO(2), and pH levels. One patient in group 1 who developed
      pneumothorax and one patient in group 2 who had steroid-related psychosis could
      not complete the study. RESULTS: Both groups showed significant improvements in
      PaO(2) and FEV(1) levels, but these were more marked in group 2 (p = 0.012 and p
      = 0.019, respectively). There was a significant increase in FVC levels in group 2
      only (p = 0.003). Group 2 also had a more marked improvement in dyspnea on
      exertion. There was no difference between the two groups with regards to other
      parameters, including pH, PaCO(2) levels, and other symptom scores. Six patients
      in group 1 and five patients in group 2 developed new exacerbations within the
      following 6 months. Hyperglycemia occurred in two patients in each group.
      CONCLUSION: In severe COPD exacerbations, a 10-day course of steroid treatment is
      more effective than a 3-day course in improving the outcome, but has no benefit
      in reducing exacerbation rates.

PMID- 11243950
TI  - Early detection of COPD in a high-risk population using spirometric screening.
AB  - STUDY OBJECTIVES: To evaluate the efficacy of mass spirometry use for the
      detection of airflow obstruction in a high-risk population. DESIGN: Free
      spirometry was offered to smokers who were > 39 years of age with a smoking
      history of > 10 pack-years. Action was preceded by the dissemination of
      information on the causes and symptoms of COPD in the local mass media. SETTING:
      Pulmonary outpatient clinics in 12 large cities of Poland. PARTICIPANTS: Eleven
      thousand twenty-seven subjects with the following characteristics were screened:
      mean (+/- SD) age, 51.8 +/- 12.5 years; men, 57%; current or ex-smokers, 80%; and
      mean smoking history, 26.1 +/- 16.8 pack-years. INTERVENTIONS: Smoking history,
      simple spirometry (FVC and FEV(1)), and an antismoking advice. RESULTS:
      Spirometric signs of airway obstruction were found in 24.3% of the subjects who
      were screened. Of those subjects, mild obstruction was found in 9.5%, moderate
      obstruction was found in 9.6%, and severe obstruction was found in 5.2%. In
      smokers aged > or = 40 years who had a smoking history of > 10 pack-years, airway
      obstruction was found in 30.6%. Airway obstruction was present in 8.3% of smokers
      < 40 years of age who had a smoking history of < 10 pack-years. Of the 2,200
      subjects who had never smoked in their lives, airway obstruction was found in
      14.4%. CONCLUSIONS: Mass spirometry in high-risk groups is an effective and easy
      method for the early detection of COPD.

PMID- 11243952
TI  - The direct medical costs of alpha(1)-antitrypsin deficiency.
AB  - BACKGROUND: For individuals with emphysema because of severe alpha(1)-antitrypsin
      deficiency, specific therapy called IV augmentation therapy has been available
      since 1989. Such therapy consists of IV infusion of pooled human plasma alpha(1)
      antiprotease. METHODS: To assess the direct medical costs of having alpha(1)
      antitrypsin deficiency, the current study surveyed members of the Alpha One
      Foundation Registry for Individuals With alpha(1)-Antitrypsin Deficiency
      regarding their annual expenditures for treatment of this disease. Data regarding
      demographic features, alpha(1)-antitrypsin status, and health-resource
      utilization were collected from a self-administered questionnaire. Respondents
      were asked to provide total health-care expenditures, but costs by specific items
      of care (eg, drugs, physician visits, etc) were not available. RESULTS: Mean
      annual cost estimates were higher for PI*ZZ-phenotype individuals ($30,948, n =
      292) than for non-PI*ZZ-phenotype individuals ($20,673, n = 53; p = 0.049). Among
      PI*ZZ-phenotype individuals, self-reported costs of health-care services were
      further analyzed for those 288 individuals whose alpha(1)-antiprotease use status
      was reported. For the 185 current alpha(1)-antiprotease users, the mean annual
      cost was $40,123 (median, $36,000). CONCLUSIONS: Annual health-care expenditures
      by individuals with alpha(1)-antitrypsin deficiency are very high, whether or not
      they are currently receiving augmentation therapy. Augmentation therapy adds
      substantial costs, especially for heavier individuals who are receiving weekly
      infusions.

PMID- 11243951
TI  - Longitudinal follow-up of patients with alpha(1)-protease inhibitor deficiency
      before and during therapy with IV alpha(1)-protease inhibitor.
AB  - BACKGROUND: The efficacy of IV augmentation therapy with human alpha(1)-protease
      inhibitor (alpha(1)-Pi) in patients with severe alpha(1)-Pi deficiency is still
      under debate. STUDY OBJECTIVES: To evaluate the progression of emphysema in
      patients with alpha(1)-Pi deficiency before and during a period in which they
      received treatment with alpha(1)-Pi. DESIGN: Multicenter, retrospective cohort
      study. SETTING: Outpatient clinics of 26 university clinics and pulmonary
      hospitals. PATIENTS: Ninety-six patients with severe alpha(1)-Pi deficiency
      receiving weekly augmentation therapy with human alpha(1)-Pi, 60 mg/kg of body
      weight, had a minimum of two lung function measurements before and two lung
      function measurements after augmentation therapy was started. Lung function data
      were followed up for a minimum of 12 months both before and during treatment
      (mean, 47.5 months and 50.2 months, respectively). MEASUREMENTS AND RESULTS:
      Patients were grouped according to the severity of their lung function
      impairment. The change in FEV(1) was compared during nontreatment and treatment
      periods. In the whole group, the decline in FEV(1) was significantly lower during
      the treatment period (49.2 mL/yr vs 34.2 mL/yr, p = 0.019). In patients with
      FEV(1) > 65%, IV alpha(1)-Pi treatment reduced the decline in FEV(1) by 73.6
      mL/yr (p = 0.045). Seven individuals had a rapid decline of FEV(1) before
      treatment, and the loss in FEV(1) could be reduced from 256 mL/yr to 53 mL/yr (p
      = 0.001). CONCLUSION: Some patients with severe alpha(1)-Pi deficiency and well
      preserved lung function show a rapid decline in FEV(1). These patients profit
      from weekly IV therapy with human alpha(1)-Pi and have less rapid decline if
      treated. Early detection of patients at risk and early start of augmentation
      therapy may prevent accelerated loss of lung tissue.

PMID- 11243953
TI  - The gene polymorphism of tumor necrosis factor-beta, but not that of tumor
      necrosis factor-alpha, is associated with the prognosis of sarcoidosis.
AB  - OBJECTIVES: Few genetic markers for the prognosis of sarcoidosis have been found.
      Tumor necrosis factor (TNF)-alpha has been implicated in the pathogenesis of
      sarcoidosis. Induced TNF-alpha or TNF-beta levels have been shown to be
      associated with the polymorphisms of the TNF genes. We investigated the roles of
      such polymorphisms in the development and prolongation of sarcoidosis. SUBJECTS
      AND MEASUREMENTS: One hundred ten Japanese patients with sarcoidosis and 161
      control subjects were genotyped for three biallelic polymorphisms in the promoter
      region of TNF-alpha gene by direct sequencing of polymerase chain reaction (PCR)
      products. A polymorphism of the TNF-beta gene (TNFB*1/TNFB*2) was detected by
      NCO: I restriction fragment length polymorphism analysis of PCR products spanning
      intron 1 and exon 2 of the TNF-beta gene. RESULTS: None of the polymorphisms
      conferred susceptibility to sarcoidosis. However, our study identified the allele
      TNFB*1, detected by the presence of a NCO: I restriction site, as a marker of
      prolonged clinical course, with the resolution of sarcoidosis being defined as
      the disappearance of all clinical symptoms, physical signs of active lesions,
      abnormal chest radiograph findings, and abnormal results of pulmonary function
      and biochemical tests. When the probability of remission in patients homozygous
      for TNFB*2 was defined as 1.00, it was 0.48 (95% confidence interval, 0.26 to
      0.88; p < 0.05) in patients with TNFB*1 (genotypes TNFB*1/1 and TNFB*1/2).
      CONCLUSIONS: The TNFB*1 allele is a marker for prolonged clinical course in
      patients with sarcoidosis. Our study is the first to link a cytokine gene
      polymorphism to the prognosis of sarcoidosis.

PMID- 11243954
TI  - Frequency of cystic fibrosis transmembrane conductance regulator gene mutations
      and 5T allele in patients with allergic bronchopulmonary aspergillosis.
AB  - STUDY OBJECTIVE: To assess the frequency of cystic fibrosis transmembrane
      conductance regulator (CFTR) gene mutations in patients with allergic
      bronchopulmonary aspergillosis (ABPA). DESIGN: Case-control study. All subjects
      in the study were screened for the presence of 13 mutations in the CFTR gene
      (R117H, 621 + 1G(-)>T, R334 W, Delta F508, Delta I507, 1717-1G(-)>A, G542X,
      R553X, G551D, R1162X, 3849 + 10kbC(-)>T, W1282X, and N1303K). Moreover, they were
      also screened for the presence of the 5T variant in intron 8. SETTING: University
      hospital and community-based hospital. PATIENTS: Twenty-one white patients with
      ABPA participated in the study. The presence of CFTR mutations was also
      investigated in 43 white subjects with allergic asthma who did not show
      sensitization to Aspergillus fumigatus and in 142 subjects seeking genetic
      counseling for diseases other than cystic fibrosis (CF). RESULTS: Six patients
      with ABPA were found to be heterozygous for one CFTR mutation, including Delta
      F508 (n = 2), G542X (n = 1), R1162X (n = 1), 1717-1G(-)>A (n = 1), and R117H (n =
      1). The 5T allele was not detected in ABPA patients. None of the ABPA patients
      showed sweat chloride concentrations > 60 mEq/L. The frequency of CFTR mutation
      carriers was significantly higher in ABPA patients (6 of 21 patients; 28.5%) than
      in control asthmatic subjects (2 of 43 subjects; 4.6%; p = 0.01) and in subjects
      seeking genetic counseling (6 of 142 subjects; p < 0.001). CONCLUSION: These
      findings indicate that in patients without a clinical diagnosis of CF, CFTR gene
      mutations could be involved in the development of ABPA, in association with other
      genetic or environmental factors.

PMID- 11243955
TI  - Endotracheal/endobronchial metastases : clinicopathologic study with special
      reference to developmental modes.
AB  - BACKGROUND: Endotracheal/endobronchial metastases (EEMs) from nonpulmonary
      neoplasms are rare. However, their definition and developmental modes have not
      yet been fully elucidated. METHODS: EEMs were defined as documented nonpulmonary
      neoplasms metastatic to the subsegmental or more proximal central bronchus, in a
      bronchoscopically visible range. The clinical and pathologic features of 16 cases
      were reviewed, with special emphasis on the developmental modes based on five
      criteria: location in the tracheobronchial tree, number of lesions, laterality of
      lesions, depth of lesions, and relationship with the associated bronchus.
      RESULTS: The developmental modes were proposed on the basis of the above five
      criteria as follows: type I, direct metastasis to the bronchus; type II,
      bronchial invasion by a parenchymal lesion; type III, bronchial invasion by
      mediastinal or hilar lymph node metastasis; and type IV, peripheral lesions
      extended along the proximal bronchus. Primary tumors included colorectal in six
      patients, breast in three patients, uterus in two patients, osteosarcoma of the
      bone in two patients, and maxillary, larynx, and parotid carcinoma in one patient
      each, respectively. The mean recurrence interval was 65.3 months. The
      developmental modes were as follows: type I, five patients; type II, one patient;
      type III, four patients; and type IV, nine patients. Three patients underwent
      surgical resection. One patient has remained well for 5 years after operation.
      Median and mean survival times were 9 months and 15.5 months, respectively.
      CONCLUSION: The mean recurrence interval was long at 65.3 months, but the mean
      survival time was short at 15.5 months. Type I accounted for only 5 of 16
      patients. Type II was found in only one patient. It is thought that this type is
      a rare form. Type IV affected nine patients. Treatment plans must be
      individualized, because in some cases, long-term survival can be expected.

PMID- 11243956
TI  - BAL neopterin : a novel marker for cell-mediated immunity in patients with
      pulmonary tuberculosis and lung cancer.
AB  - BACKGROUND: Neopterin is derived from guanosine triphosphate and is produced by
      stimulated macrophages under the influence of gamma-interferon of lymphocyte
      origin. It has been suggested that it is an excellent marker for the activation
      of the monocyte/macrophage axis in some clinical situations. However, to our
      knowledge, the relationship of BAL neopterin levels to disease states has not
      been studied. AIM: To assess the usefulness of BAL neopterin levels as an index
      of disease activity in patients with pulmonary tuberculosis and lung cancer.
      METHODS: BAL and serum neopterin levels were evaluated in 20 patients with
      pulmonary tuberculosis, 20 patients with bronchogenic carcinoma, and 10 healthy
      individuals. The concentration of neopterin was evaluated by radioimmunoassay
      technique. The BAL level of neopterin was standardized using the BAL urea level.
      RESULTS: The neopterin levels (mean +/- SD) in the BAL and serum of tuberculous
      patients (88.6 +/- 27.4 nmol/L epithelial lining fluid [ELF], 61.3 +/- 29.4
      nmol/L, respectively) were significantly higher when compared with those in lung
      cancer patients (40.7 +/- 16.6 nmol/L ELF, 26.8 +/- 6.58 nmol/L, respectively, p
      < 0.001) and when compared with those in control subjects (26.3 +/- 11.3 nmol/L
      ELF, 6.8 +/- 2.7 nmol/L, respectively, p < 0.001). In the tuberculous group, BAL
      and serum neopterin levels in patients with far-advanced disease were
      significantly higher when compared with those in patients with moderately and
      minimally advanced diseases (p < 0.001). BAL and serum neopterin levels were
      significantly higher in patients with small cell carcinoma than in those with
      adenocarcinoma (p < 0.05). BAL neopterin levels were significantly (p < 0.001)
      higher than serum levels in all patients and control groups. In addition, there
      were significant positive correlations between BAL and serum neopterin levels in
      tuberculous (r = 0.92, p < 0.001), lung cancer (r = 0.62, p < 0.001), and control
      groups (r = 0.93, p < 0.001). CONCLUSIONS: The levels of neopterin in BAL fluid
      may reflect the degree of disease activity in pulmonary tuberculous patients. In
      addition, BAL neopterin levels are elevated in patients with lung cancer,
      especially the small-cell carcinoma type.

PMID- 11243957
TI  - Endobronchial argon plasma coagulation for treatment of hemoptysis and neoplastic
      airway obstruction.
AB  - STUDY OBJECTIVE: To evaluate the usefulness of endobronchial argon plasma
      coagulation (APC) for the treatment of hemoptysis and neoplastic airway
      obstruction. DESIGN: Retrospective study. SETTING: Bronchoscopy unit of a
      university hospital. PATIENTS: A total of 60 patients with bronchogenic carcinoma
      (n = 43), metastatic tumors affecting the bronchi (n = 14), or benign bronchial
      disease (n = 3). Indications for intervention were hemoptysis (n = 31),
      symptomatic airway obstruction (n = 14), and both obstruction and hemoptysis (n =
      25). Hemoptysis was stratified as a volume of > 200 mL/d (n = 6), > 50 to 200
      mL/d (n = 23), or < or = 50 mL/d but persistence for > 1 week (n = 27). The mean
      (+/- SD) duration of hemoptysis was 16.5 +/- 16.1 days before intervention.
      Obstruction sites were the trachea (n = 8), mainstem bronchi (n = 21), and lobar
      bronchi (n = 30). In 24 cases, the patient had obstructions at multiple sites.
      The mean size of the pretreatment obstruction was 76 +/- 24.9%. INTERVENTIONS:
      APC, a noncontact form of electrocoagulation, was performed via flexible
      bronchoscopy. Sixty patients underwent 70 procedures. Conscious sedation without
      endotracheal intubation was used in all patients except four, who were
      mechanically ventilated because of underlying respiratory failure. MEASUREMENTS
      AND RESULTS: All patients with hemoptysis experienced a resolution of bleeding
      immediately after APC. Hemoptysis from treated sites did not recur during a mean
      follow-up duration of 97 +/- 91.9 days. Patients with endoluminal airway lesions
      had an overall decrease in mean obstruction size to 18.4 +/- 22.1%. All patients
      with obstructive lesions, except one who died of sepsis, experienced symptom
      improvement. In these patients, symptom control was maintained during a median
      follow-up period of 53 days (range, 18 to 321 days). There were no complications
      related to the procedure. CONCLUSIONS: APC is effective for the treatment of
      endoluminal hemoptysis and airway obstruction. The procedure can be performed in
      an outpatient setting or at the bedside in the ICUs. APC provides a simpler,
      lower-risk alternative to other interventional endobronchial techniques.

PMID- 11243958
TI  - Hemoptysis in patients with renal insufficiency : the role of flexible
      bronchoscopy.
AB  - STUDY OBJECTIVES: To assess the indications, yield, and therapeutic impact of
      flexible bronchoscopy (FB) in patients with hemoptysis and renal insufficiency.
      DESIGN: Retrospective cohort analysis. SETTING: Tertiary-care university
      hospital. PATIENTS: Thirty-four patients over a 7.5-year period who underwent FB
      to evaluate hemoptysis in the setting of renal insufficiency (ie, serum
      creatinine level, > 1.5 mg/dL). MEASUREMENTS AND RESULTS: The etiology of
      hemoptysis was undetermined in 41% of cases. Defined causes of bleeding included
      infections (29%), pulmonary renal syndromes (15%), airway injury (9%), and
      pulmonary embolism (6%). No specific bleeding site was identified, but FB
      lateralized hemorrhaging to one lung in 24% of patients. FB results influenced
      therapy in 29% of patients overall and in 8% of patients without respiratory
      tract infection. The hospital survival rate was 47% and did not differ based on
      the presence or absence (presence vs absence) of the following variables: a
      defined etiology for hemoptysis (45% vs 50%); lateralized bleeding (38% vs 50%);
      or management alterations prompted by other FB findings (50% vs 46%). Factors
      associated with survival included the onset of bleeding prior to hospital
      admission (80% vs 33%; p = 0.02), the absence of respiratory failure requiring
      mechanical ventilation at the time of FB (90% vs 29%; p = 0.002), and lack of
      prohemorrhagic factors (other than uremia) such as disseminated intravascular
      coagulation, recent treatment with warfarin, heparin, or antiplatelet agents (78%
      vs 33%; p = 0.05). During the 6 months following hospital discharge, hemoptysis
      recurred in 14% of patients, and 5 patients died, for an overall mortality rate
      of 62%. CONCLUSIONS: These data suggest that FB in hospitalized patients with
      hemoptysis and renal insufficiency, and without radiographic findings suggesting
      neoplastic disease, has a low yield and limited impact. Whether FB influences
      outcome in selected patients in this setting requires prospective investigation.

PMID- 11243959
TI  - Symptomatic persistent post-coronary artery bypass graft pleural effusions
      requiring operative treatment : clinical and histologic features.
AB  - BACKGROUND: More than 85% of patients develop pleural effusions after coronary
      artery bypass grafting (CABG). Although the majority resolve spontaneously, post
      CABG effusions can persist. The cause of these persistent effusions is unknown,
      and the histology of the pleural changes has seldom been reported. OBJECTIVES: To
      describe the patient characteristics and pathologic condition of the pleural
      tissues in patients with persistent post-CABG effusions. SUBJECTS: Eight patients
      with persistent post-CABG effusions who underwent thoracoscopy or thoracotomy
      over a 2-year period by one thoracic surgeon. These eight patients were selected
      as having undergone CABG > 2 months before their thoracic surgery and had no
      other identifiable causes of effusion. RESULTS: The median time from CABG to
      pleural surgery was 132 days (range, 74 to 2,258 days). The median left
      ventricular ejection fraction was 57% (range, 15 to 70%). All patients were
      dyspneic and had large (> or = 25% of the hemithorax) effusions on chest
      radiograph. All effusions persisted after two or more thoracenteses. Pleural
      effusion was left sided in three patients and bilateral in five patients. Pleural
      fluid was characterized by lymphocytosis (82 to 99%). Four of the eight patients
      had a visceral peel and trapped lung requiring decortication. Seven of the eight
      biopsy specimens showed pleural thickening characterized by dense fibrous tissues
      with associated mononuclear cell infiltration, while the eighth biopsy specimen
      showed only clotted blood. The degree of inflammation and fibrosis correlated
      with the interval between CABG and pleural surgery. Early post-CABG patients
      displayed more inflammation, with abundant lymphocytes in nodular configuration
      deep in the fibrous tissues away from the surface. Abundant keratin-positive,
      spindle-shaped cells were present in the fibrous tissues. Late cases showed
      predominantly mature fibrosis. CONCLUSIONS: Persistent post-CABG effusion can
      occur. Pleural fluids and pleural tissue in early-stage lesions were
      characterized by lymphocytosis. With time, the inflammatory changes were replaced
      by fibrosis that resulted in dyspnea and, at times, trapped lungs requiring
      surgical intervention.

PMID- 11243960
TI  - Thoracoscopy talc poudrage : a 15-year experience.
AB  - OBJECTIVES: To review our experience with thoracoscopy and talc poudrage during
      the previous 15 years with regards to efficacy, side effects, morbidity, and
      mortality. METHODS: Six hundred fourteen consecutive patients (58.6% female; mean
      age, 54.5 years) underwent thoracoscopy with talc poudrage from August 1983 to
      May 1999. Of these, 457 patients had malignant pleural effusions, 108 patients
      had benign pleural effusions, and 49 patients had spontaneous pneumothorax.
      RESULTS: Sixty-four patients were excluded from evaluation for efficacy: 30
      patients (4.9%) because the lung did not expand at the time of the procedure and
      34 patients (5.5%) because they died within 30 days of the thoracoscopy. All
      exclusions were in the malignant group. The overall success rate of the 393
      patients with malignant pleural effusions was 93.4%, while the overall success
      for the 108 patients with benign effusions was 97%, although 7 patients (7%) with
      benign effusions required a second thoracoscopy. The success rate with
      pneumothorax was 100%. Major morbidity included empyema in 4%, reexpansion
      pulmonary edema in 2.2%, and respiratory failure 1.3%. CONCLUSION: Thoracoscopy
      with talc poudrage is effective in producing a pleurodesis in malignant and
      benign pleural effusion and in spontaneous pneumothorax. However, it should be
      noted that the insufflation of talc has a systemic distribution associated with a
      low rate of morbidity and perhaps does induce ARDS, which is sometimes fatal in a
      small percentage of patients. Because of these side effects, the search for a
      better agent should be continued.

PMID- 11243961
TI  - Aggressive diuresis for severe heart failure in the elderly.
AB  - STUDY OBJECTIVE: To determine the efficacy, safety, and economic benefit of
      continuous IV infusion of furosemide as a treatment modality for elderly patients
      with class IV heart failure. DESIGN: Prospective trial of consecutively admitted
      elderly patients > 65 years old with class IV heart failure. SETTING: A single
      cardiovascular service in a university medical center. PATIENTS: Seventeen male
      and female patients > 65 years old consecutively admitted to a cardiovascular
      service. RESULTS: High-dose, continuous IV infusion of furosemide was successful
      in providing a 9- to 20-L diuresis in an average of 3.5 days without causing
      clinical complications or aberrations in blood chemistry. The length of stay was
      2.3 days shorter than a contemporary group of class III and class IV elderly
      patients with heart failure managed on other medical services. The Medicare
      reimbursement for heart failure was $6,047. Patients receiving IV bolus diuretic
      therapy incurred billing charges of $10,193, or a loss of $4,146 per patient to
      the hospital. Patients receiving diuretic infusion therapy incurred billing
      charges of $4,944. This was a difference of $5,249 per patient treated by
      continuous IV infusion compared to bolus therapy and a profit per Medicare
      patient of $1,103. Therefore, a $4,146 billing loss was converted to $1,103
      profit. CONCLUSION: IV furosemide infusion therapy for class IV heart failure in
      the elderly is a safe, effective, and economic mode of therapy.

PMID- 11243962
TI  - Significance of end-tidal P(CO(2)) response to exercise and its relation to
      functional capacity in patients with chronic heart failure.
AB  - OBJECTIVES: The value of end-tidal PCO(2) monitoring during exercise in patients
      with chronic heart failure has not been elucidated. The present study was
      designed to examine end-tidal PCO(2) response to exercise and its relation to
      functional capacity in patients with chronic heart failure. METHODS AND RESULTS:
      Maximal upright ergometer exercise with respiratory gas analysis and arterial
      blood gas analysis were performed in 105 patients with chronic heart failure (34
      patients in New York Heart Association [NYHA] class I, 38 patients in NYHA class
      II, and 33 patients in NYHA class III) and 14 normal control subjects. Peak O(2)
      uptake, excessive exercise ventilation as assessed by the slope of the relation
      between expired minute ventilation and CO(2) output (VE-VCO(2)), and the ratio of
      physiologic dead space to tidal volume (VD/VT) were determined. Cardiac output
      was also measured during exercise in 28 patients with chronic heart failure.
      Arterial PO(2) or PCO(2) values at rest and during exercise were not different
      among the four groups. However, end-tidal PCO(2) was significantly lower, and
      arterial to end-tidal PCO(2) difference and VD/VT were significantly higher in
      NYHA class III patients than other groups during exercise. The maximal end-tidal
      PCO(2) during exercise was significantly reduced as the severity of chronic heart
      failure advanced (45.7 +/- 4.0 mm Hg in normal control subjects, 43.5 +/- 4.8 mm
      Hg in NYHA class I patients, 39.7 +/- 5.1 mm Hg in NYHA class II patients, and
      34.9 +/- 5.3 mm Hg in NYHA class III patients). The maximal end-tidal PCO(2)
      during exercise was significantly correlated with peak O(2) uptake (r = 0.68; p <
      0.001) and maximal cardiac index (r = 0.73; p < 0.001), and inversely related to
      Ve-VCO(2) (r = - 0.84; p < 0.001) and VD/VT at peak exercise (r = -0.65; p <
      0.001). CONCLUSIONS: The decreased end-tidal PCO(2) during exercise, which is
      caused by high ventilation/perfusion ratio mismatching, reflects both reduced
      cardiac output response to exercise and increased exercise ventilation due to
      enlarged physiologic dead space in advanced chronic heart failure. The end-tidal
      PCO(2) during exercise can be used to evaluate the functional capacity of
      patients with chronic heart failure.

PMID- 11243963
TI  - Prognostic factors in medically treated patients with chronic pulmonary embolism.
AB  - OBJECTIVE: To evaluate risk factors in medically treated patients with chronic
      pulmonary embolism (CPE) who are not suitable candidates for definitive surgical
      therapy. STUDY DESIGN: A total of 53 consecutive patients with angiographically
      confirmed CPE were involved. Four patients underwent pulmonary endarterectomy,
      and 49 patients received continuous anticoagulation therapy and were followed up
      over an average period of 18.7 months (range, 6 to 72 months). RESULTS: Sixteen
      patients died during the follow-up period, mostly from progressive right
      ventricle failure. Among the nonsurvivors, 12.5% had distal CPE and 87.5% had
      proximal CPE (p = 0.03). The survivors had a higher (mean +/- SD) level of PaO(2)
      (59.3 +/- 11 mm Hg) than the nonsurvivors (50.8 +/- 9 mm Hg; p = 0.02), a lower
      mean pulmonary artery pressure (mPAP; 30.3 +/- 15 mm Hg vs 51 +/- 21 mm Hg; p =
      0.0004), a lower hematocrit value (40.0 +/- 6 vs 44.2 +/- 6; p = 0.03), and
      better exercise tolerance (4.8 +/- 3 multiples of resting O(2) consumption [METs]
      vs 2.5 +/- 1 METs; p = 0.02) achieved during the maximal symptom-limited
      exercise. The patients with coexisting COPD had a higher mortality rate (62.5%)
      than those without COPD (37.5%; p = 0.04). Independent risk factors in the Cox
      analysis were as follows: mPAP (p = 0.04), exercise tolerance (p = 0.02), and
      COPD (p = 0.04). In the Kaplan-Meier analysis, the patient group with lower
      mortality achieved > 2 METs (p = 0.02) and had mPAP < 30 mm Hg (p = 0.04).
      CONCLUSION: The prognosis for the medically treated CPE patients, particularly
      those with pulmonary hypertension, was unfavorable. The prognostic factors for
      these patients were mPAP, coexistence of COPD, and severe exercise intolerance.

PMID- 11243964
TI  - A noninvasive assessment of pulmonary perfusion abnormality in patients with
      primary pulmonary hypertension.
AB  - STUDY OBJECTIVES: The ventilatory equivalent for CO(2) (ie, the ratio of minute
      ventilation [VE] to carbon dioxide output [VCO(2)]) is increased in patients with
      primary pulmonary hypertension (PPH) consequent to an increase in physiologic
      dead space and alveolar ventilation. We wished to see whether the VE/V(2) ratio
      correlated with the abnormality in pulmonary hemodynamics in PPH patients and
      whether it changed in response to prostacyclin infusion. METHODS: Following right
      sided heart catheterization, 10 patients with severe PPH were studied in the
      coronary-care unit while hemodynamic and gas exchange measurements were measured
      simultaneously before and after infusion with epoprostenol (Epo), a prostacyclin
      analog. Studies were performed at baseline and during IV infusion of two to three
      increasing dosages of Epo in 10 PPH patients (NYHA class III-IV). Four patients
      had radial artery catheters for simultaneous blood gas measurements. Nine healthy
      subjects who were matched by sex, height, and weight underwent gas exchange
      analyses only. RESULTS: The mean (+/- SD) VE/VCO(2) ratio was higher in PPH
      patients than in control subjects (50.7 +/- 9.7 vs 30.6 +/- 3.8; p < 0.001).
      Thirteen measurements made in four patients showed that the VE/VCO(2) ratio
      correlated with the physiologic dead space/tidal volume ratio (r = 0.78; p =
      0.002). The VE/VCO(2) ratio measurement at baseline correlated significantly with
      total pulmonary vascular resistance (TPVR) (r = 0.70; p = 0.02) but not with mean
      pulmonary artery pressure (mPAP) or cardiac index. During Epo infusion, the
      VE/VCO(2) ratio decreased with increasing dosage in 6 of 10 patients, with no
      change or slight increases in the 4 remaining patients. Considering all doses,
      the VE/VCO(2) ratio decreased significantly in response to the short-term
      administration of Epo. The decrease tended to parallel the pattern of decrease in
      TPVR, but the changes in both variables were too small to provide a statistically
      significant correlation. The mPAP did not change significantly in response to Epo
      infusion, although TPVR did change at the highest dosage. CONCLUSIONS: In
      patients with severe PPH, the VE/VCO(2) ratio correlated significantly with TPVR
      but not with mPAP or cardiac index. The VE/VCO(2) ratio decreased systematically
      from baseline with the dose of Epo in some but not all patients. The VE/VCO(2)
      ratio and TPVR decreased significantly in response to Epo when all doses were
      considered. Further studies are needed to elucidate whether noninvasive gas
      exchange measurements may be clinically useful in the evaluation of the severity
      of pulmonary vascular disease and the effectiveness of pulmonary vasodilator
      therapy.

PMID- 11243965
TI  - Acceptability of short-course rifampin and pyrazinamide treatment of latent
      tuberculosis infection among jail inmates.
AB  - STUDY OBJECTIVES: To determine whether short-course treatment of latent
      tuberculosis infection (LTBI) with 2 months of rifampin and pyrazinamide (2RZ) is
      well tolerated and leads to increased treatment completion among jail inmates, a
      group who may benefit from targeted testing and treatment for LTBI but for whom
      completion of > or = 6 months of isoniazid treatment is difficult because of the
      short duration of incarceration. DESIGN: Prospective cohort. SETTING: Large,
      urban county jail. PATIENTS: All inmates admitted to the Fulton County Jail who
      had positive tuberculin skin test results, normal findings on chest radiography,
      and expected duration of incarceration of at least 60 days. INTERVENTION: Inmates
      were offered 2RZ via daily directly observed therapy for 60 doses as an
      alternative to isoniazid therapy. MEASUREMENTS AND RESULTS: We measured the
      completion of 2RZ treatment and toxicity due to 2RZ treatment during
      incarceration. From December 14, 1998, through December 13, 1999, 1,360 new
      inmates had positive tuberculin skin test results and normal findings on chest
      radiography, and 168 new inmates had an expected duration of incarceration of >
      or = 60 days. One hundred sixty-six inmates (> 99%) were HIV-negative. Eighty-one
      inmates (48%) completed 60 doses of 2RZ treatment while incarcerated. Seventy
      four inmates (44%) were released before completion. Treatment was stopped in 1
      inmate (< 1%) for asymptomatic elevation of asparginine aminotransferase (> or =
      10 times normal) and in 12 inmates (7%) for minor complaints. Twenty-one inmates
      had completed isoniazid treatment in the year before the availability of 2RZ, and
      9 inmates completed isoniazid treatment in the year during the availability of
      2RZ. CONCLUSIONS: 2RZ was acceptable to and well tolerated by inmates, and led to
      a marked increase in the number of inmates completing treatment of LTBI during
      incarceration.

PMID- 11243966
TI  - Pulmonary cytomegalovirus infection in immunocompromised patients.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection and CMV disease are frequent
      complications in immunocompromised patients. In this study, the incidence of
      pulmonary CMV infection was analyzed in different groups of immunocompromised
      patients and the diagnostic value of immunostaining with anti-CMV antibodies in
      BAL cells was evaluated in regard to the diagnosis of CMV pneumonitis. METHODS:
      Five hundred eighty consecutive BAL procedures were analyzed prospectively in 442
      immunocompromised and 126 nonimmunocompromised control subjects. CMV culture in
      BAL fluid was performed by shell vial assay and immunostaining using three
      monoclonal anti-CMV antibodies. RESULTS: The incidence of culture results
      positive for CMV in the BAL fluid varied from 20 to 30% in HIV-positive patients,
      in patients following stem cell or renal transplantation, and in patients with
      autoimmune disease or lung fibrosis treated with immunosuppressive agents. CMV
      was cultured from 4.4% of BALs in patients treated with high-dose chemotherapy
      and from 2.4% of control subjects. CMV disease developed in 37 patients; in 18 of
      these patients, CMV pneumonitis was present. The results of CMV immunostaining
      were positive in a total of 22 BALs, all in patients with CMV disease. The
      sensitivity, specificity, and positive and negative predictive values of positive
      CMV immunostaining results for the diagnosis of CMV pneumonitis were 88.9%,
      98.6%, 72.7%, and 99.5%, respectively. CONCLUSION: The incidence of pulmonary CMV
      infection is similar in different groups of immunocompromised patients except for
      patients following high-dose chemotherapy. CMV immunostaining in the BAL fluid is
      a very helpful method to diagnose CMV pneumonitis in these patients.

PMID- 11243967
TI  - Prognostic markers of short-term mortality in AIDS-associated Pneumocystis
      carinii pneumonia.
AB  - BACKGROUND: Since 1990, corticosteroids have been recommended as adjunctive
      therapy for patients with AIDS-associated Pneumocystis carinii pneumonia (PCP)
      and respiratory failure. We hypothesized that the natural course of AIDS
      associated PCP has changed in the era of adjunctive corticosteroid therapy.
      OBJECTIVE: To study variables obtained on hospital admission for possible
      prognostic value of short-term (3-month) outcome of PCP. DESIGN AND PATIENTS:
      Prospective observational study of 176 consecutive HIV-1-infected individuals
      with PCP between 1990 and 1999. METHOD: Cox proportional-hazards regression
      models. RESULTS: Univariate analysis showed that age, one or more prior episodes
      of PCP, use of antimicrobial therapy other than trimethoprim-sulfamethoxazole
      (TMP-SMZ), use of PCP prophylaxis at diagnosis, and culture of cytomegalovirus
      (CMV) in BAL predicted progression to death within 3 months. After adjustment,
      age (relative risk [RR], 4.1; 95% confidence interval [CI], 1.8 to 9.3), initial
      antimicrobial therapy other than TMP-SMZ (RR, 3.1; 95% CI, 1.2 to 8.5), use of
      PCP prophylaxis (RR, 5.6; 95% CI, 2.2 to 14.4), and culture of CMV in BAL fluid
      (RR, 2.7; 95% CI, 1.3 to 5.6) remained independent predictors of a poor outcome.
      In contrast, neither PO(2) nor serum lactate dehydrogenase, which in earlier
      studies were identified as prognostic markers, were predictors of mortality.
      CONCLUSION: Age, initial anti-PCP therapy, use of PCP prophylaxis, and BAL CMV
      status may be useful predictors of outcome of PCP in patients treated in the era
      of adjunctive corticosteroid therapy.

PMID- 11243968
TI  - Smoking, respiratory symptoms, and diseases : a comparative study between
      northern Sweden and northern Finland: report from the FinEsS study.
AB  - STUDY OBJECTIVES: The influences of different smoking categories on the
      prevalence of respiratory symptoms, asthma, and chronic bronchitis have been
      examined in the most northern province of Sweden, Norrbotten, and in Lapland,
      Finland. The two areas have similar geographic and demographic conditions.
      METHODS AND STUDY POPULATION: The study is a part of the FinEsS studies, which
      are epidemiologic respiratory surveys in progress in Sweden, Finland, and
      Estonia. A random sample of 20- to 69-years-olds were invited to answer a postal
      questionnaire about respiratory symptoms, smoking habits, and occupation. In
      Norrbotten, 8,333 subjects were invited and 7,104 responded (85%). In Lapland,
      8,005 were invited and 6,633 responded (83%). RESULTS: The participation by age
      and sex was similar in both countries. The prevalence of smokers in Lapland was
      32% vs 26% in Norrbotten. Significantly more women than men in Norrbotten were
      smokers, while the opposite was true for Lapland. Sputum production was the most
      prevalent symptom in both areas, 25% in Lapland vs 19% in Norrbotten. The
      prevalence of chronic productive cough was 11% in Lapland and 7% in Norrbotten.
      Bronchitic symptoms were more prevalent in Lapland among both smokers and
      nonsmokers. A positive family history of chronic obstructive airway disease
      together with increased number of consumed cigarettes showed an additive effect
      for both chronic productive cough and wheezing. The odds ratio (OR) for wheezing
      during the last 12 months was 3.8 for subjects without a family history of
      obstructive airway disease who consumed > 14 cigarettes per day compared with
      nonsmokers, but if the subjects had a family history of obstructive airway
      disease, the risk for wheezing increased to OR 8.4. CONCLUSION: Bronchitic
      symptoms were more common in Finland. The difference remained also after
      correction for demographic variables including smoking habits, age and
      socioeconomic group, and family history of obstructive airway disease. Identical
      methods, sample composition, and the high participation rate contribute to the
      validity of the results. Air pollution, including environmental tobacco smoke,
      may contribute to the difference. To explain the difference, further analysis and
      investigations of social and environmental factors as well as genetic factors are
      needed.

PMID- 11243969
TI  - Systemic antibiotics fail to clear multidrug-resistant Klebsiella from a
      pediatric ICU.
AB  - STUDY OBJECTIVES: To determine the magnitude of infection rate and antimicrobial
      resistance in a pediatric ICU (PICU), and to evaluate the efficacy of using broad
      spectrum antibiotics. DESIGN: A 3-month, prospective, observational cohort audit.
      SETTING: A 12-bed tertiary, referral PICU. PATIENTS OR PARTICIPANTS: All children
      admitted to the PICU for > 72 h. INTERVENTIONS: Surveillance cultures of throat
      and rectum on admission and once weekly thereafter. MEASUREMENTS AND RESULTS: Of
      the 150 admissions during the 3-month period, a total of 52 patients (24 girls
      and 28 boys) requiring mechanical ventilation for a minimum of 3 days were
      enrolled in the audit. The median age and interquartile range (IQR) was 17 months
      (IQR, 5.8 to 63); length of stay, 6.5 days (IQR, 4 to 13); ventilation days, 5
      (IQR, 3 to 11); pediatric risk of mortality score, 14 (IQR, 9 to 19); and risk of
      mortality, 0.03 (IQR, 0.014 to 0.087). Fifteen patients (29%) developed 21
      infections, mainly lower-airway infections and septicemias. Of the 52 children, 7
      children carried multidrug-resistant bacteria and 3 patients progressed to
      develop four infections with those resistant bacteria. Of the seven carriers, six
      patients carried gentamicin-resistant Klebsiella. Methicillin-resistant
      Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae and
      gentamicin-resistant Pseudomonas aeruginosa each were carried by one child. Six
      of those nine resistant isolates were present in the admission flora. Despite the
      potent combination of piperacillin/tazobactam and amikacin, three children
      acquired the multidrug-resistant Klebsiella while in the PICU and became
      nosocomial carriers. CONCLUSIONS: Only surveillance cultures allow the
      distinction between import of multidrug-resistance and resistant bacteria
      acquired while in PICU. In this study, two thirds of the resistant isolates were
      imported. The introduction of newer potent systemic antibiotic combinations
      failed to control the endemic reservoir of multidrug-resistant Klebsiella and
      suggests that such policies have little impact.

PMID- 11243970
TI  - Respiratory changes in aortic blood velocity as an indicator of fluid
      responsiveness in ventilated patients with septic shock.
AB  - STUDY OBJECTIVE: To investigate whether the respiratory changes in peak velocity
      (Vpeak) of aortic blood flow could be related to the effects of volume expansion
      on cardiac index. DESIGN: Prospective clinical study. SETTING: Medical ICUs of a
      university hospital (20 beds) and of a nonuniversity hospital (15 beds).
      PATIENTS: Nineteen sedated septic shock patients who were receiving mechanical
      ventilation and who had preserved left ventricular (LV) systolic function.
      INTERVENTION: Volume expansion. MEASUREMENTS AND RESULTS: Analysis of aortic
      blood flow by transesophageal echocardiography allowed beat-to-beat measurement
      of Vpeak before and after volume expansion. Maximum values of Vpeak (Vpeakmax)
      and minimum values of Vpeak (Vpeakmin) were determined over one respiratory
      cycle. The respiratory changes in Vpeak (Delta Vpeak) were calculated as the
      difference between Vpeakmax and Vpeakmin divided by the mean of the two values
      and were expressed as a percentage. The indexed LV end-diastolic area (EDAI) and
      cardiac index were obtained at the end of the expiratory period. The volume
      expansion-induced increase in cardiac index was > or = 15% in 10 patients
      (responders) and < 15% in 9 patients (nonresponders). Before volume expansion,
      Delta Vpeak was higher in responders than in nonresponders (20 +/- 6% vs 10 +/-
      3%; p < 0.01), while EDAI was not significantly different between the two groups
      (9.7 +/- 3.7 vs 9.7 +/- 2.4 cm(2)/m(2)). Before volume expansion, a Delta Vpeak
      threshold value of 12% allowed discrimination between responders and
      nonresponders with a sensitivity of 100% and a specificity of 89%. Volume
      expansion-induced changes in cardiac index closely correlated with the Delta
      Vpeak before volume expansion (r(2) = 0.83; p < 0.001). CONCLUSION: Analysis of
      respiratory changes in aortic blood velocity is an accurate method for predicting
      the hemodynamic effects of volume expansion in septic shock patients receiving
      mechanical ventilation who have preserved LV systolic function.

PMID- 11243971
TI  - Increased endothelial injury in septic patients with coronary artery disease.
AB  - STUDY OBJECTIVE: Recently, it was proposed that soluble intercellular adhesion
      molecule (sICAM)-1 plasma levels may allow subgroup identification of patients at
      risk for cardiovascular complications during sepsis. However, the impact of
      preexisting coronary artery disease (CAD) on these results has not yet been
      tested. The aim of this study was to investigate whether plasma levels of
      adhesion molecules, nitric oxide, and cytokines differ between septic patients
      with or without preexisting CAD. DESIGN: Prospective study. SETTING: Surgical
      ICU. PATIENTS: Forty-four septic patients, 24 of whom met the criteria of CAD.
      MEASUREMENT: Hemodynamic measurements were performed and blood samples were taken
      within 12 h after onset of sepsis (early sepsis) and again 72 h thereafter (late
      sepsis). Soluble adhesion molecules and cytokines were determined using
      commercially available enzyme-linked immunosorbent assay kits, cyclic
      guanosinomonophosphate (cGMP) by competitive radioimmunoassay, and
      nitrite/nitrate photometrically by Griess reaction. RESULTS: In CAD patients,
      sICAM-1 (p < 0.02) was significantly elevated in early and late sepsis, whereas
      soluble endothelial-linked adhesion molecule (sE-selectin; p < 0.01) and cGMP (p
      < 0.03) were only increased in late sepsis. Oxygen consumption did not
      significantly differ between groups. Oxygen delivery and mixed venous oxygen
      saturation during early and late sepsis were significantly diminished and the
      oxygen extraction ratio significantly increased in the CAD group (p < 0.05).
      CONCLUSIONS: Increased endothelial injury may be indicated by the elevated levels
      of sICAM-1, sE-selectin, and cGMP in septic patients with preexisting CAD. These
      parameters, however, failed to serve as predictors for unknown CAD or chances for
      survival in early sepsis.

PMID- 11243972
TI  - Incidence and predictors of ARDS after cardiac surgery.
AB  - BACKGROUND: Severe pulmonary injury with the development of ARDS is a potential
      complication of cardiac surgery and cardiopulmonary bypass (CPB). STUDY
      OBJECTIVES: This retrospective, case-control study was designed to determine the
      incidence and mortality of ARDS after cardiac surgery and CPB, as well as to
      identify preoperative and perioperative predisposing factors of this
      complication. METHODS: Of 3,278 patients who underwent cardiac surgery and CPB
      between January 1995 and December 1998, 13 patients developed ARDS during the
      postoperative period. Each patient was matched with four or five control subjects
      who had the same type of surgery on the same day but did not develop
      postoperative respiratory complications. RESULTS: The incidence of ARDS was 0.4%,
      with an ARDS mortality of 15%. In the ARDS group, 38% had previous cardiac
      surgery, as compared to 3.5% in the control group (p < 0.002). During the
      postoperative period, ARDS patients received more blood products (4 +/- 5 vs 2 +/
      3; p < 0.01) and developed shock more frequently (31% vs 5%; p < 0.02) than
      patients in the control group. Multivariate regression analysis identified
      previous cardiac surgery, shock, and the number of transfused blood products as
      significant independent predictors for ARDS, with odds ratios of 31.5 (p =
      0.015), 10.8 (p = 0.03), and 1.6 (p = 0.03), respectively. CONCLUSIONS: ARDS
      following cardiac surgery and CPB was a rare complication that carried a 15%
      mortality rate. Previous cardiac surgery, shock, and number of blood products
      received are important predicting factors for this complication.

PMID- 11243974
TI  - Extubation failure in a large pediatric ICU population.
AB  - OBJECTIVE: To review a large population of children receiving mechanical
      ventilation to establish a baseline rate of extubation success and failure and to
      identify those characteristics that place a patient at greater risk of failing
      planned extubation. DESIGN: Retrospective chart review. SETTING: University
      affiliated children's hospital with a 20-bed pediatric ICU. PATIENTS: All 632
      patients receiving mechanical ventilation during the 2-year period from July 1,
      1996, to June 30, 1998. METHOD: Patients receiving mechanical ventilation were
      identified via a computerized database. Charts were reviewed of all patients who
      were reintubated within 72 h of extubation. MEASUREMENTS AND RESULTS: There were
      548 planned extubation events, of which 521 were successful. Twenty-seven
      patients failed planned extubation at least once; only the first attempt at
      extubation was included in the analysis. The failure rate of planned extubations
      was 4.9%. Including only patients who had received mechanical ventilation for >
      24 h before extubation, the failure rate was 6.0%. For patients intubated > 48 h,
      the failure rate was 7.9%. The patients who failed extubation were found to be
      significantly younger and to have received mechanical ventilation longer than
      those who succeeded, in both the analysis of all patients receiving mechanical
      ventilation and the subgroup of those receiving mechanical ventilation > 24 h.
      When only patients who had received mechanical ventilation for > 48 h were
      analyzed, the difference in age was no longer significant, but the duration of
      ventilation before extubation was still significantly longer for those who
      failed. CONCLUSION: We determined the overall failure rate of planned extubations
      in a large population of pediatric patients to be 4.9%. Those patients who were
      younger and had received mechanical ventilation longer were more at risk for
      extubation failure.

PMID- 11243973
TI  - Adrenal insufficiency in high-risk surgical ICU patients.
AB  - STUDY OBJECTIVES: To examine the incidence and response to treatment of adrenal
      insufficiency (AI) in high-risk postoperative patients. DESIGN: Prospective
      observational case series. SETTING: Large urban tertiary-care surgical ICU
      (SICU). PARTICIPANTS: Adults > 55 years of age who required vasopressor therapy
      after adequate volume resuscitation in the immediate postoperative period.
      INTERVENTIONS: Each patient underwent a cosyntropin (ACTH) stimulation test; at
      the discretion of the clinical team, some patients were empirically given
      hydrocortisone (100 mg IV q8h for three doses) before serum cortisol values
      became available. MEASUREMENTS: Adrenal dysfunction (AD), defined as serum
      cortisol < 20 microg/dL at all time points, with Delta cortisol (60 min post-ACTH
      minus baseline) of < or = 9 microg/dL; functional hypoadrenalism (FH), defined as
      serum cortisol < 30 microg/dL at all time points or Delta cortisol (60 min post
      ACTH minus baseline) < or = 9 microg/dL; and AI, as the presence of either AD or
      FH. RESULTS: One hundred four patients were enrolled with a mean age (SD) of 65.2
      +/- 16.9 years. AI (AD plus FH) was found in 34 of 104 patients (32.7%): AD was
      found in 9 patients (8.7%), FH in 25 patients (24%), and normal adrenal function
      in 70 patients (67.3%). The absolute eosinophil count was significantly higher in
      the combined AD and FH groups compared with the group with normal adrenal
      function (p < 0.05). Forty-six of 104 patients (44.2%) received hydrocortisone;
      29 (63%) could be weaned from treatment with vasopressors within 24 h. This
      beneficial effect of hydrocortisone reached statistical significance in the FH
      group when compared with untreated patients (p < 0.031); a similar trend was seen
      in the AD group (p = 0.083). Mortality was also lower in the hydrocortisone
      treated AI patients (5 of 23 [21%] vs 5 of 11 [45%] in those not receiving
      hydrocortisone; p < 0.01). CONCLUSION: There is a high incidence of AI among SICU
      patients > 55 years of age with postoperative hypotension requiring vasopressors.
      There is also a significant association between hydrocortisone replacement
      therapy, resolution of vasopressor requirements, and improved survival.

PMID- 11243976
TI  - Stress testing in cardiac evaluation : current concepts with emphasis on the ECG.

PMID- 11243975
TI  - Long-term arterial cannulation in ICU patients using the radial artery or
      dorsalis pedis artery.
AB  - STUDY OBJECTIVES: To evaluate the rate of arterial thrombosis and catheter
      related infection following radial artery or dorsalis pedis artery (DPA)
      cannulations lasting > or = 4 days. DESIGN: Prospective, observational study of
      two cohorts of ICU patients. SETTING: ICU of a university hospital. PATIENTS: In
      a first group of 131 consecutive patients, the DPA was selected for arterial
      cannulation. In the second group, 134 consecutive patients were considered for
      radial artery cannulation. MEASUREMENTS AND RESULTS: In the DPA group, the
      overall success rate for catheter placement was 85%. Patients were cannulated for
      16 +/- 5 days (mean +/- SD). In the radial artery group, the overall success rate
      was 97.7% (129 of 132 patients; p < 0.0001 vs DPA group). Patients were
      cannulated for 13.3 +/- 4.0 days. In both groups, no signs of ischemia were
      detected at the clinical examination. In the DPA group, no thrombosis was
      detected at the angiographic examination in 21 patients (38%), a thrombosis
      without vessel obstruction was observed in 21 patients (31%), and a thrombosis
      with vessel obstruction was observed in 21 patients (31%). In the radial artery
      group, no thrombosis was observed in 31 patients (24%; not significant vs DPA
      group), a partial thrombosis was found in 73 patients (57%), and a total
      thrombosis with vessel obstruction was found in 25 patients (19%). Two cases of
      catheter-related infection were observed in the DPA group. In the radial artery
      group, four cases of catheter-related infection were diagnosed vs DPA group (not
      significant). CONCLUSIONS: The rate of serious complications was similar for both
      sites of arterial cannulation. Accepting a 12.7% lower rate of successful
      placement, the DPA route provides a safe and easily available alternative when
      radial arteries are not accessible.

PMID- 11243977
TI  - Clinical aspects of respiratory muscle dysfunction in the critically ill.

PMID- 11243978
TI  - Long-term ventilation for patients with Duchenne muscular dystrophy : physicians'
      beliefs and practices.
AB  - STUDY OBJECTIVES: Although long-term ventilation (LTV) has been shown to extend
      the lives of individuals with Duchenne muscular dystrophy (DMD), initiating LTV
      is still considered controversial. The purpose of the study was to describe the
      LTV-related attitudes and practices of Canadian physicians who follow up patients
      with DMD. DESIGN: The study consisted of a mail questionnaire supplemented by
      face-to-face interviews. PARTICIPANTS: Forty-five physicians who follow up
      patients with DMD through Canadian neuromuscular clinics. MEASUREMENTS: A mail
      questionnaire of 66 closed-ended questions related to practice and attitudes was
      completed by all respondents. Qualitative semistructured interviews were
      conducted with six volunteer physicians, and were audiotaped and transcribed.
      RESULTS: The results indicated that 25.0% of physicians do not discuss LTV with
      all of their DMD patients. The most frequently cited reason for advising against
      LTV was poor patient quality of life (52.6%). Three themes emerged from the
      qualitative data: mentioning and discussing LTV are discrete events with
      different purposes, nighttime and full-time LTV decisions are approached
      differently, and physicians modify their discussions to influence outcome.
      CONCLUSIONS: The study demonstrated considerable agreement among the physicians
      regarding disclosure practices. Concerns are raised by the number of physicians
      who do not disclose to all patients and families and the role of quality-of-life
      judgments in decision making. It is suggested that because of their subjective
      nature, quality-of-life judgments should not be made without the participation of
      the patient and family, and that an initial disclosure is the minimum requirement
      of informed consent/decision making.

PMID- 11243979
TI  - Lung mass in a smoker.

PMID- 11243980
TI  - Positron emission tomography in the staging of small-cell lung cancer : a
      preliminary study.
AB  - STUDY OBJECTIVES: Small-cell lung cancer (SCLC) has an unfavorable prognosis,
      especially when the disease is extensive at presentation. Accurate staging
      procedures are therefore needed for treatment planning. Positron emission
      tomography (PET) is a modern noninvasive imaging technique, the value of which
      for the staging of SCLC was investigated in the present study. SETTING:
      University hospital. PATIENTS: Thirty-one patients with suspected lung cancer
      were investigated for staging purposes using chest radiography, CT of the thorax
      and abdomen, abdominal ultrasound, and bone scanning. Twenty-five patients also
      received PET examinations during the staging procedures. Five of these patients
      were found to have SCLC, while two patients had mixed lesion types. Further
      analysis of the latter group was carried out. RESULTS: PET detected the primary
      tumor in all patients, and lymph nodes in five patients. All lymph nodes were
      proved to be malignant by endoscopic ultrasonography-guided fine-needle
      aspiration. Only one patient had distant metastases, which were detected by both
      CT and PET. CONCLUSIONS: PET appears be a suitable imaging method in SCLC. A
      potential role for the technique as a standard staging procedure will need to be
      tested by investigating a larger number of patients in a prospective study.

PMID- 11243981
TI  - A 52-year-old woman with recurrent hemoptysis.

PMID- 11243982
TI  - Recurrent mitral stenosis : problems of management.

PMID- 11243983
TI  - Atresia of the trachea following repeated percutaneous dilational tracheotomy.
AB  - Percutaneous dilational tracheotomy (PDT) and conventional tracheostomy are still
      competing methods to provide an airway for intensive care patients requiring
      assisted ventilation. Tracheal stenosis is a late complication for any
      tracheostomy and long-term intubation. However, late complications in PDT have
      not been extensively studied. This article is the first to report on total
      atresia of the subglottic larynx and cervical trachea after PDT. The dimension of
      the lesion is visualized by three-dimensional reconstructed CT scan. The etiology
      of this condition is discussed.

PMID- 11243984
TI  - Somatostatin in the treatment of chylothorax.
AB  - A case report is presented of spontaneous chylothorax successfully treated by
      conservative means. The helpful role of the inhibitory peptide, octreotide, is
      discussed.

PMID- 11243985
TI  - Treatment of pulmonary artery compression due to fibrous mediastinitis with
      endovascular stent placement.
AB  - We present the case of a 32-year-old woman with high-grade right pulmonary artery
      stenosis secondary to fibrous mediastinitis. The patient was managed with balloon
      angioplasty and stent placement. Only 15 cases of this nature have been reported
      in the literature, and this is one of the first to be managed with endovascular
      stent placement.

PMID- 11243986
TI  - Chronic eosinophilic pneumonia presenting with recurrent massive bilateral
      pleural effusion : case report.
AB  - We describe a rare case of a 29-year-old woman with chronic eosinophilic
      pneumonia (CEP) presenting with massive bilateral pleural effusion leading to
      respiratory failure, a complication that was not reported before with CEP. The
      patient was successfully managed with ventilatory support and steroid therapy. On
      long-term follow-up, she remained well, receiving a low maintenance dose of
      prednisone without evidence of relapse of the disease.

PMID- 11243987
TI  - One-year continuous inhaled nitric oxide for primary pulmonary hypertension.
AB  - We describe a case of long-term administration of nitric oxide (NO) in a 32-year
      old man who was admitted with exertional dyspnea and anasarca. A diagnosis of
      primary pulmonary hypertension was made. An acute vasodilator trial with inhaled
      NO showed a 5% reduction of the mean pulmonary artery pressure. Long-term NO
      inhalation therapy was initiated. Twenty days later, the dyspnea improved, the
      anasarca resolved, and the PaO(2) level increased. After 12 months of NO therapy,
      the patient remained stable and no signs of toxicity or tachyphylaxis were
      observed. To our knowledge, this is the first report of 1 year of continuously
      inhaled NO in an adult patient with primary pulmonary hypertension. These
      findings suggest that prolonged NO therapy might be an effective alternative, at
      a lower cost, to the continuous IV infusion of epoprostenol.

PMID- 11243988
TI  - Pregnancy and primary pulmonary hypertension : successful outcome with
      epoprostenol therapy.
AB  - Primary pulmonary hypertension (PPH) associated with pregnancy carries a high
      maternal mortality rate. Short-term epoprostenol infusion has been demonstrated
      to improve the hemodynamic profile in patients with PPH. We report a successful
      maternal-fetal outcome with epoprostenol therapy during pregnancy, cesarean
      section, and postpartum in a patient with PPH. Epoprostenol therapy did not
      produce any physical or developmental abnormalities in the fetus. A favorable
      maternal-fetal outcome may occur with a multidisciplinary approach.

PMID- 11243989
TI  - Late mediastinal shift after repeated aspiration of postpneumonectomy seroma.
AB  - Development of a postoperative seroma is a frequent complication after muscle
      sparing thoracotomy. We describe an unusual case of late mediastinal shift in a
      patient in whom our original plan to perform a limited muscle-sparing thoracotomy
      was abandoned. The procedure was converted to a standard posterolateral incision
      to perform a pneumonectomy for a large central carcinoid tumor with
      extrabronchial extension. Fluid that accumulated in her pneumonectomy space
      presumably shifted into the dissected tissues of her chest wall, and was then
      drained repeatedly by her local physician in the time interval between 2 weeks
      and 3 months after surgery.

PMID- 11243990
TI  - Multiple aseptic pulmonary nodules with central necrosis in association with
      pyoderma gangrenosum.
AB  - Pulmonary manifestations of pyoderma gangrenosum are relatively rare. We report
      the case of a 45-year-old patient with multiple pulmonary nodules with central
      necrosis as assessed by CT scan. The patient had a 4-year history of pyoderma
      gangrenosum with only minor skin manifestations. A CT-guided, fine-needle biopsy
      of the lung revealed a nonspecific, inflammatory, aseptic necrotic process, which
      was comparable to the skin biopsy of one pyoderma lesion. Following the
      initiation of oral prednisolone therapy, a rapid resolution of the pulmonary
      nodules occurred. We conclude that pulmonary nodules represent a rare pulmonary
      manifestation of pyoderma gangrenosum.

PMID- 11243991
TI  - Recurrent pulmonary sarcoidosis in HIV-infected patients receiving highly active
      antiretroviral therapy.
AB  - HIV infection and sarcoidosis occur in the same age group, but there are only a
      few reports of the coexistence of the two disorders in the same individual. This
      infrequent occurrence has been attributed to the paucity of functioning CD4(+)
      lymphocytes required for granuloma formation in patients with HIV infection. We
      report two patients with a history of remote sarcoidosis who later in life
      contracted HIV infection and developed recurrent, progressive pulmonary
      sarcoidosis while receiving highly active antiretroviral therapy (HAART).
      Progressive pulmonary sarcoidosis should be added to the differential diagnosis
      in patients receiving HAART for HIV infection who develop diffuse lung disease
      with recovery of CD4(+) lymphocyte population.

PMID- 11243992
TI  - Malignant pleural mesothelioma produces functional granulocyte-colony stimulating
      factor.
AB  - We report a patient with diffuse malignant pleural mesothelioma showing marked
      elevation of neutrophils. The level of serum granulocyte-colony stimulating
      factor (G-CSF) was elevated (138 pg/mL; normal range, < 20 pg/mL). The patient
      died 6 weeks after disease progression had been noted, and immunohistochemistry
      using a specific monoclonal antibody against recombinant G-CSF at autopsy
      demonstrated that the malignant mesothelioma cells actually produced G-CSF. Only
      three cases of malignant pleural mesothelioma, including the current patient,
      have been reported to produce G-CSF. We demonstrated an elevated serum level of G
      CSF and G-CSF-bearing tumor cells by immunochemistry.

PMID- 11243993
TI  - Fluticasone and cortisol measurements.

PMID- 11243994
TI  - Brahms' illness.

PMID- 11243995
TI  - Salmeterol and conventional asthma therapy.

PMID- 11243996
TI  - Regularly scheduled inhaled bronchodilators and maintenance asthma therapy.

PMID- 11243997
TI  - Compliance with bronchodilator treatment.

PMID- 11243998
TI  - Pleural to serum cholinesterase ratio in separation of transudative and exudative
      pleural effusions.

PMID- 11243999
TI  - Intralobar pulmonary sequestration.

PMID- 11244000
TI  - Reality-based medicine--the response.

PMID- 11244001
TI  - Syncope in a patient with cervical tumor and prolonged QT interval.

PMID- 11244003
TI  - Effect of N-acetyl-seryl-aspartyl-lysyl-proline on DNA and collagen synthesis in
      rat cardiac fibroblasts.
AB  - N:-Acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a natural inhibitor of
      pluripotent hematopoietic stem cell entry into the S phase of the cell cycle and
      is normally present in human plasma. Ac-SDKP is exclusively hydrolyzed by ACE,
      and its plasma concentration is increased 5-fold after ACE inhibition in humans.
      We examined the effect of 0.05 to 100 nmol/L Ac-SDKP on 24-hour (3)H-thymidine
      incorporation (DNA synthesis) by cardiac fibroblasts both in the absence and
      presence of 5% FCS. Captopril (1 micromol/L) was added in all cases to prevent
      the degradation of Ac-SDKP. Treatment of cardiac fibroblasts with 5% FCS
      increased thymidine incorporation from a control value of 12 469+/-594 to 24
      598+/-1051 cpm (P:<0.001). Cotreatment with 1 nmol/L Ac-SDKP reduced stimulation
      to control levels (10 373+/-200 cpm, P:<0.001). We measured hydroxyproline
      content and incorporation of (3)H-proline into collagenous fibroblast proteins
      and found that Ac-SDKP blocked endothelin-1 (10(-8) mol/L)-induced collagen
      synthesis in a biphasic and dose-dependent manner, causing inhibition at low
      doses, whereas high doses had little or no effect. It also blunted the activity
      of p44/p42 mitogen-activated protein kinase in a biphasic and dose-dependent
      manner in serum-stimulated fibroblasts, suggesting that the inhibitory effect of
      DNA and collagen synthesis may depend in part on blocking mitogen-activated
      protein kinase activity. Participation of p44/p42 in collagen synthesis was
      confirmed, because a specific inhibitor for p44/p42 activation (PD 98059, 25
      micromol/L) was able to block endothelin-1-induced collagen synthesis, similar to
      the effect of Ac-SDKP. The fact that Ac-SDKP inhibits DNA and collagen synthesis
      in cardiac fibroblasts suggests that it may be an important endogenous regulator
      of fibroblast proliferation and collagen synthesis in the heart. Ac-SDKP may
      participate in the cardioprotective effect of ACE inhibitors by limiting
      fibroblast proliferation (and hence collagen production), and therefore it would
      reduce fibrosis in patients with hypertension.

PMID- 11244004
TI  - Role of myocytes in myocardial collagen production.
AB  - Excessive collagen deposition may cause abnormal stiffness of the heart during
      hypertrophy and heart failure. The potent vasoconstrictor angiotensin II seems,
      via an unknown mechanism, to stimulate collagen production. This study describes
      the in vitro and ex vivo effects of [Sar(1)]Ang II on collagen production by
      fibroblasts in culture and in beating, nonworking heart preparations. The effects
      of [Sar(1)]Ang II on isolated rat hearts or rat heart fibroblasts were determined
      by quantifying transcript levels of collagen phenotypes I and III through
      videodensitometry after Northern blot analysis with specific cDNA probes
      (collagen [P alpha( 2)r(2)] rat alpha( 2)[I] probe for type I and human skin
      fibroblast alpha(1)[III] probe for type III). When [Sar(1)]Ang II was added in
      vitro to neonatal or adult 28-week-old Wistar-Kyoto rat heart fibroblasts,
      questionable stimulation in the mRNAs of types I and III occurred. In contrast,
      when 10(-8) mol/L [Sar(1)]Ang II was added to beating, nonworking Wistar-Kyoto
      rat heart preparation ex vivo, a 1.5- to 2.5-fold stimulation of collagen mRNAs
      of phenotypes I and III was observed. When neonatal fibroblasts were cocultured
      with neonatal myocytes in vitro, with 10(-10) mol/L [Sar(1)]Ang II added, there
      was no stimulation of either phenotype. However, significant stimulation of both
      collagen transcripts was recorded when 10(-10) mol/L [Sar(1)]Ang II was added to
      adult fibroblasts cocultured with either neonatal or adult myocytes. Our data
      suggest that factors produced by myocytes are necessary for upregulation of
      collagen genes in vitro and demonstrate that fibroblast-myocyte cross-talk is
      required for Ang II-induced collagen upregulation.

PMID- 11244005
TI  - Regulation of cardiac collagen: angiotensin and cross-talk with local growth
      factors.

PMID- 11244006
TI  - Arterial pressure, left ventricular mass, and aldosterone in essential
      hypertension.
AB  - The purpose of the present study was to evaluate the relationship of aldosterone
      to blood pressure and left ventricular size in black American (n=109) and white
      French Canadian (n=73) patients with essential hypertension. Measurements were
      obtained with patients off antihypertensive medications and included 24-hour
      blood pressure monitoring, plasma renin activity and aldosterone, and an
      echocardiogram. Compared with the French Canadians, the black Americans had
      higher body mass indexes, higher systolic blood pressures, attenuated nighttime
      reduction of blood pressure, and lower serum potassium concentrations (P:<0.01
      for each). Left ventricular mass index, posterior wall thickness,
      interventricular septal thickness, and relative wall thickness were also greater
      (P:<0.01 for each) in the black American patients. Supine and standing plasma
      renin activity was lower (P:<0.01 and P:<0.05, respectively) in the black
      Americans, whereas supine plasma aldosterone concentrations did not differ, and
      standing plasma aldosterone was greater (P:<0.05) in the black Americans (9.2+/
      0.7 ng/dL) than in the French Canadians (7.3+/-0.6 ng/dL). In the black
      Americans, supine plasma aldosterone was positively correlated with nighttime
      systolic (r=0.30; P:<0.01) and diastolic (r=0.39; P:<0.001) blood pressures and
      inversely correlated with the nocturnal decline of systolic (r=-0.29; P:<0.01)
      and diastolic (r=-0.37; P:<0.001) blood pressures. In the black Americans,
      standing plasma aldosterone was positively correlated with left ventricular mass
      index (r=0.36; P:<0.001), posterior wall thickness (r=0.33; P:<0.01), and
      interventricular septal thickness (r=0.26; P:<0.05). When the black American
      patients were divided into obese and nonobese groups, significant correlations
      between plasma aldosterone and both blood pressure and cardiac mass were observed
      only in the obese. In the French Canadians, overall, plasma aldosterone did not
      correlate with either blood pressure or any measures of heart size. However,
      among obese French Canadians, supine plasma aldosterone correlated with nighttime
      diastolic (r=0.53, P:<0.02) and systolic (r=0.44, P:<0.01) blood pressures but
      not with cardiac mass. These results are consistent with the hypothesis that
      aldosterone contributes to elevated arterial pressure in obese black American and
      obese white French Canadian patients with essential hypertension and to the
      attenuated nocturnal decline of blood pressure and left ventricular hypertrophy
      in obese, hypertensive black Americans.

PMID- 11244007
TI  - Ace D/I polymorphism and incidence of post-PTCA restenosis: a prospective,
      angiography-based evaluation.
AB  - Early restenosis is the major complication of percutaneous transluminal coronary
      angioplasty (PTCA), occurring in approximately 30% of all initially successful
      procedures. The D/I polymorphism of the ACE gene, which has variably been
      reported to represent a risk factor for manifestations of ischemic heart disease,
      has recently been implicated in the pathophysiology of restenosis after PTCA by
      some investigators but not by others. All studies conducted thus far involved
      relatively small sample sizes. We investigated the possible association of ACE
      D/I genotype and post-PTCA restenosis in a large, prospective sample of patients
      followed by quantitative coronary angiography. The ACE D/I gene polymorphism was
      characterized in a cohort of 779 patients, of whom 342 (cases) had developed
      restenosis (as defined by >50% loss of lumen compared with immediate
      postprocedure results) at repeat quantitative coronary angiography at 6 months
      after PTCA. Allele frequencies for the ACE D and I: alleles were 0.58 and 0.42 in
      cases and 0.58 and 0.42 in control subjects. All observed genotype frequencies
      were in Hardy-Weinberg equilibrium. There was no evidence for an association
      between genotype and restenosis or degree of lumen loss. The data from this
      largest study of its kind conducted so far provide no evidence for an association
      of the ACE D/I allelic polymorphism with incidence of restenosis after PTCA. On
      the basis of the power of this study, we conclude that in a general population,
      the ACE D/I polymorphism is not a useful marker to assess risk of post-PTCA
      restenosis.

PMID- 11244008
TI  - Adverse cardiac effects of salt with fludrocortisone in hypertension.
AB  - The effect of salt on blood pressure (BP) is controversial. A more important
      question is whether salt can produce cardiac target-organ damage, irrespective of
      its effect on BP. We assessed the effect of salt with fludrocortisone on QT
      dispersion and echocardiographic left ventricular diastolic function in a
      prospective interventional study involving 29 hypertensive subjects with a raised
      aldosterone/renin ratio who were hospitalized for investigation of possible
      primary aldosteronism. Each subject over 4 days was given a total of 28.8 g (480
      mmol) of sodium chloride and 1.5 mg of fludrocortisone with potassium
      supplementation. Baseline and posttreatment 12-lead ECGs and echocardiograms were
      obtained. There were no significant changes in body weight, pulse rate, or BP
      after treatment with salt and fludrocortisone. Plasma sodium was significantly
      increased from 141.4 (SD 2.1) to 142.6 (SD 2.4) mmol/L (P:=0.001). QT and QTc
      dispersion both significantly increased: +19.6 (SD 16.5) ms (95% CI, 13.4 to
      25.9) (P:<0.001) and +19.8 (SD 20.9) ms (95% CI, 11.8 to 27.7) (P:<0.001),
      respectively. There were no significant changes in (n=15) left ventricular
      dimensions or systolic function, but all diastolic filling indexes, including the
      preload-independent index, flow propagation velocity (55.49 [SD 10.91] to 48.96
      [SD 11.40] cm/s, P:=0.018) worsened, suggesting significant deterioration of left
      ventricular diastolic function with salt and fludrocortisone. In conclusion, a
      combination of salt with fludrocortisone increased QT dispersion and impaired
      left ventricular diastolic relaxation in hypertensive patients with high
      aldosterone/renin ratios. This raises the possibility that salt may have BP
      independent adverse cardiac effects in susceptible hypertensive subjects.

PMID- 11244009
TI  - Antiadrenergic effects of adenosine in pressure overload hypertrophy.
AB  - In the present study, we sought to evaluate whether the antiadrenergic action of
      adenosine in the heart is altered in pressure overload hypertrophy produced in
      rats by suprarenal aortic banding. Epicardial and coronary effluent adenosine and
      inosine concentrations and release were significantly elevated in compensated
      pressure overload hypertrophy but not in hearts with left ventricular failure. In
      pressure overload hearts, the contractile response to beta-adrenergic stimulation
      was less inhibited by incremental concentrations of either adenosine or the
      selective A(1) receptor agonist chloro-N:(6)-cyclopentyl adenosine than in
      controls. Furthermore, the extent of desensitization to the antiadrenergic
      actions of adenosine in pressure overload hypertrophy appeared to be proportional
      to the extent of chamber dilation and dysfunction. A 60-minute infusion of
      adenosine produced a sustained antiadrenergic effect that lasted up to 45 minutes
      after the infusion was terminated in both controls and hearts with compensated
      hypertrophy. This effect was not observed in the decompensated left ventricular
      failure group. Subsequent infusion with adenosine of the A(2A) receptor
      antagonist 8-(3-chlorostyryl)-caffeine to counteract the proadrenergic effect of
      A(2A) receptor stimulation did not alter the decreased sensitivity to the
      antiadrenergic actions of adenosine in hypertrophied hearts. Finally, isolated
      myocytes from hypertrophied hearts demonstrated a decreased ability to suppress
      isoproterenol-elicited increases in [Ca(2+)](i) transients in the presence of
      adenosine and the A(2A) receptor antagonist compared with myocytes from control
      hearts. Myocardial adenosine concentrations increase during the compensated phase
      of pressure overload hypertrophy but then decrease when there is evidence of
      decompensation. The antiadrenergic actions of adenosine transduced via the
      myocardial A(1) receptor are diminished in pressure overload hypertrophied
      hearts. These factors may render these hearts more vulnerable to the detrimental
      effects of chronically increased sympathetic activity.

PMID- 11244010
TI  - Predominance of isolated systolic hypertension among middle-aged and elderly US
      hypertensives: analysis based on National Health and Nutrition Examination Survey
      (NHANES) III.
AB  - The purpose of the present study was to examine patterns of systolic and
      diastolic hypertension by age in the nationally representative National Health
      and Nutrition Examination Survey (NHANES) III and to determine when treatment and
      control efforts should be recommended. Percentage distribution of 3 blood
      pressure subtypes (isolated systolic hypertension, combined systolic/diastolic
      hypertension, and isolated diastolic hypertension) was categorized for
      uncontrolled hypertension (untreated and inadequately treated) in 2 age groups
      (ages <50 and >/=50 years). Overall, isolated systolic hypertension was the most
      frequent subtype of uncontrolled hypertension (65%). Most subjects with
      hypertension (74%) were >/=50 years of age, and of this untreated older group,
      nearly all (94%) were accurately staged by systolic blood pressure alone, in
      contrast to subjects in the untreated younger group, who were best staged by
      diastolic blood pressure. Furthermore, most subjects (80%) in the older untreated
      and the inadequately treated groups had isolated systolic hypertension and
      required a greater reduction in systolic blood pressure than in the younger
      groups (-13.3 and -16.5 mm Hg versus -6.8 and -6.1 mm Hg, respectively;
      P:=0.0001) to attain a systolic blood pressure treatment goal of <140 mm Hg.
      Contrary to previous perceptions, isolated systolic hypertension was the majority
      subtype of uncontrolled hypertension in subjects of ages 50 to 59 years,
      comprised 87% frequency for subjects in the sixth decade of life, and required
      greater reduction in systolic blood pressure in these subjects to reach treatment
      goal compared with subjects in the younger group. Better awareness of this middle
      aged and older high-risk group and more aggressive antihypertensive therapy are
      necessary to address this treatment gap.

PMID- 11244011
TI  - Angiotensinogen polymorphisms and elevated blood pressure in the general
      population: the Copenhagen City Heart Study.
AB  - In the present study, we tested the hypothesis that the Met235Thr and Thr174Met
      mutations were associated or not with elevated blood pressure. We genotyped 9100
      women and men from the Danish general population, of whom 54% had elevated blood
      pressure. Of the 9100, 41% and 12% carried the Thr235 and Met174 mutations,
      respectively; the Met174 mutation always occurred on the same allele as the
      Thr235 mutation. On multifactorial logistic regression analysis, women homozygous
      for Thr235 versus noncarriers had an odds ratio for elevated blood pressure of
      1.29 (95% CI 1.05 to 1.58), which increased to 1.50 (1.15 to 1.96) if they also
      were homozygous for Thr174 (noncarrier of Met174). Women homozygous for Thr235
      also had an increased risk of isolated elevated systolic blood pressure (1.37;
      1.02 to 1.84) and of mild blood pressure elevation (1.40; 1.10 to 1.77). We found
      no statistically significant association between elevated blood pressure and
      genotype in men or among genotype and systolic blood pressure, diastolic blood
      pressure, or pulse pressure in either gender. Homozygosity for both Thr235 and
      Thr174 was associated with a 10% increase in plasma angiotensinogen levels in
      both genders compared with homozygosity for Met235 and Thr174; however, systolic
      and diastolic blood pressures were positively correlated to plasma
      angiotensinogen levels in women only. In conclusion, in this large-scale study of
      the general population, double homozygosity for Thr235 and Thr174 in the
      angiotensinogen gene is associated with a 10% increase in angiotensinogen levels
      and is a risk factor for elevated blood pressure in women but not in men.

PMID- 11244012
TI  - G-protein beta(3) subunit gene (GNB3) 825T allele is associated with enhanced
      renal perfusion in early hypertension.
AB  - The C825T polymorphism of the gene encoding the G-protein beta(3) subunit (GNB3)
      is associated with increased intracellular signal transduction and arterial
      hypertension. The aim of the study was to investigate the impact of this
      polymorphism on early adaptive processes of the left ventricle and renal
      hemodynamic changes in young normotensive to mildly hypertensive subjects. Ninety
      five white male students with normal or mildly elevated blood pressure were
      genotyped for the GNB3 C825T polymorphism. In each participant, 24-hour
      ambulatory blood pressure, left ventricular structure and function (2D-guided M
      mode echocardiography), renal plasma flow (para-aminohippurate clearance),
      glomerular filtration rate (inulin clearance), and 24-hour urinary sodium
      excretion were determined. The GNB3 825T allele was not associated with casual or
      ambulatory blood pressure, parameters of left ventricular structure or function,
      glomerular filtration, or 24-hour urinary sodium excretion. However, in T:-allele
      carriers (CT+TT), renal plasma flow was higher than in CC subjects (CT/TT: 659+/
      96 versus CC: 614+/-91 mL/min, P:=0.019). ANOVA disclosed that renal plasma flow
      was independently influenced by both genotype and blood pressure, with
      hypertensives having a higher renal plasma flow than normotensive subjects. This
      was the fact irrespective of the criteria used for the definition of hypertension
      (World Health Organization or 24-hour ambulatory blood pressure criteria). The
      GNB3 825T variant is associated with increased renal perfusion in this study.
      Because early renal hemodynamic changes play a pivotal role in the pathogenesis
      of essential hypertension, our data suggest a relevance of increased G-protein
      activation in the pathogenesis of hypertension.

PMID- 11244014
TI  - Abnormal renal vascular responses to dipyridamole-induced vasodilation in
      spontaneously hypertensive rats.
AB  - The objective of this study was to determine whether there were differences in
      hemodynamic responses of different vascular beds to systemic administration of
      dipyridamole between spontaneously hypertensive (SHR) and normotensive Wistar
      Kyoto (WKY) rats. To this end, systemic hemodynamics and organ blood flows (using
      labeled microspheres) were determined in conscious rats before and 10 minutes
      after dipyridamole (4 mg. kg(-1). min(-1)) infusion. In both the normotensive and
      hypertensive rats, the dipyridamole infusion reduced arterial pressure by
      approximately 20 mm Hg, associated with a decreased total peripheral resistance
      and an increased cardiac output. Renal blood flow decreased significantly in SHR
      after dipyridamole but remained unchanged or increased slightly in the WKY rats.
      There were no other differences in regional hemodynamics, including those of
      brain, liver, skin, and muscle, between the WKY and SHR. Antihypertensive
      treatment completely restored normal renal vascular response to dipyridamole.
      Previous reports had demonstrated an abnormal coronary hemodynamic response of
      the SHR. Our data demonstrate that, as with coronary hemodynamics, hypertension
      selectively induced alterations in renal vasculature. These findings may be of
      importance in identifying the earliest hemodynamic evidence of developing
      hypertensive nephrosclerosis.

PMID- 11244013
TI  - Epoxyeicosatrienoic acid-mediated renal vasodilation to arachidonic acid is
      enhanced in SHR.
AB  - We tested the hypothesis that cyclooxygenase-independent vasodilation produced by
      arachidonic acid (AA) is mediated by epoxyeicosatrienoic acids (EETs) and is
      blunted in the spontaneously hypertensive rat (SHR). At normal perfusion pressure
      (PP; 70 to 90 mm Hg), AA constricted the renal vasculature in both SHR and
      normotensive Wistar-Kyoto rats, an effect abolished by cyclooxygenase inhibition,
      and converted to vasodilation when PP was raised to approximately 200 mm Hg.
      Unexpectedly, renal vasodilation elicited by AA was greater in the SHR at high
      PP; for example, 2.5, 5, and 10 microg of AA produced PP declines of 54+/-9, 92+/
      10, and 112+/-5 mm Hg, respectively, in SHR compared with 26+/-3, 45+/-5, and
      77+/-6 mm Hg in Wistar-Kyoto rats (P:<0.01). However, the renal vasodilator
      responses to acetylcholine (0.1 microg) and sodium nitroprusside (1 microg) did
      not differ between strains, indicating that vascular responsiveness to AA was
      independent of intrinsic changes in vascular smooth muscle. Hyperresponsiveness
      of the renal vasculature to AA may be unique for the SHR, because it did not
      occur in Sprague-Dawley rats with angiotensin II-induced hypertension. 5,8,11,14
      Eicosatetraynoic acid (ETYA; 4 micromol/L), an inhibitor of all AA pathways,
      attenuated the vasodilator responses to AA, as did treatment with stannous
      chloride, which depletes cytochrome P450 enzymes, suggesting that a cytochrome
      P450 AA metabolite mediated the renal vasodilation. N:-Methylsulfonyl-12,12
      dibromododec-11-en-amide (DDMS; 2 micromol/L), a selective omega-hydroxylase
      inhibitor, did not affect AA-induced vasodilation, whereas selective inhibition
      of epoxygenases with either miconazole (0.3 micromol/L) or N:-methylsulfonyl-6-(2
      propargyloxyphenyl) hexanamide (MS-PPOH; 12 micromol/L) did, indicating that one
      or more EETs were involved in the renal vasodilator action of AA at high PP. This
      conclusion was supported by the demonstration that AA greatly enhanced the renal
      efflux of EETs at high PP but not at basal PP.

PMID- 11244016
TI  - Genetic influences on baroreflex function in normal twins.
AB  - Blood pressure and heart rate are strongly influenced by genetic factors;
      however, despite the pivotal role of genetics in short-term cardiovascular
      regulation, little is known about the genetic contribution to baroreflex
      function. We assessed genetic influence on baroreflex sensitivity (BRS) in 149
      twin pairs (88 monozygotic of age 33+/-13 years and BMI 23+/-4 kg/m(2) and 61
      dizygotic of age 33+/-11 years and BMI 24+/-4 kg/m(2)). ECG and finger arterial
      blood pressures were measured continuously under resting conditions. BRS values
      were calculated by use of cross-spectral analysis (baroreflex slope calculated as
      mean value of transfer function between systolic blood pressure and the R-R
      interval in the low-frequency band [BRSLF] and baroreflex slope calculated as the
      mean value of transfer function between systolic blood pressure and R-R interval
      in the respiratory frequency band [BRSHF]) and the sequence technique (BRS+, BRS
      ). Heritability (h(2)) was estimated with a path-modeling approach. BRS values
      did not differ significantly between groups (monozygotic, BRSLF, 17+/-13; BRSHF,
      21+/-18; BRS+, 19+/-16; and BRS-, 21+/-15, and dizygotic, BRSLF, 16+/-9; BRSHF,
      20+/-14; BRS+, 18+/-10; and BRS-, 20+/-11 ms/mm Hg), and were significantly
      correlated (P:<0.001). When variances and covariances for monozygotic and
      dizygotic twins were compared, significant correlations were found for BRS in
      monozygotic (range, r=0.38 to 0.48) but not in dizygotic twin pairs (r=-0.03 to
      0.09). Thus, BRS is heritable; the variability can be explained by genetic
      influences (P:<0.01; h(2) range, 0.36 to 0.44). The genetic influence on BRS
      remained strong after correction for BMI and blood pressure. Therefore, BRS is
      strongly genetically determined, probably by different genes than are resting
      blood pressure and BMI.

PMID- 11244015
TI  - Early alteration in glomerular reserve in humans at genetic risk of essential
      hypertension: mechanisms and consequences.
AB  - Essential hypertension has a familial predisposition, but the phenotype of
      elevated blood pressure has delayed penetrance. Because the kidney is a crucial
      determinant of blood pressure homeostasis, we studied early glomerular
      alterations in still-normotensive young subjects at genetic risk of hypertension.
      Thirty-nine normotensive adults (mean age 29 to 31 years), stratified by genetic
      risk (parental family history [FH]) of hypertension (26 with positive FH [FH+],
      13 with negative FH [FH-]), underwent intravenous infusion of mixed amino acids.
      Before and during amino acid administration, we measured glomerular filtration
      rate (GFR), putative second messengers of amino acids (nitric oxide [NO.]
      metabolites and cGMP), serum insulin and amino acid concentrations, and the
      FE(Li)+ as an index of renal proximal tubular reabsorption. The FH+ group had a
      blunted GFR rise in response to amino acids (2.43+/-8.16% versus 31.0+/-13.4%
      rise, P:=0.0126). The amino acid-induced change in GFR correlated (r=0.786,
      P:<0.01) with the change in urinary NO. metabolite excretion; a diminished rise
      in urinary NO. metabolite excretion in the FH+ group (P:=0.0105) suggested a
      biochemical mechanism for the different GFR responses between FH groups: a
      relative inability to convert arginine to NO. The FH+ group had a far lower
      initial cGMP excretion at baseline (261+/-21.1 versus 579+/-84.9 nmol. h(-1)/1.73
      m(2), P:=0.001), although cGMP did not change during the amino acid infusion
      (P:=0.703). FH status, baseline GFR, and baseline serum insulin jointly predicted
      GFR response to amino acids (P:=0.0013), accounting for approximately 45% of the
      variance in GFR response. Decline in FE(Li)+, an inverse index of proximal
      tubular reabsorption, paralleled increase in GFR (r=-0.506, P:=0.01), suggesting
      differences in proximal tubular reabsorption during amino acids between the FH
      groups. GFR response to amino acid infusion was blunted in the FH+ group despite
      significantly higher serum concentrations of 6 amino acids (arginine, isoleucine,
      leucine, methionine, phenylalanine, and valine) in the FH+ group, suggesting a
      novel form of insulin resistance (to the amino acid-translocating action of
      insulin) in FH+ subjects. We conclude that blunted glomerular filtration reserve
      in response to amino acids is an early-penetrance phenotype seen even in still
      normotensive subjects at genetic risk of hypertension and is linked to impaired
      formation of NO. in the kidney. Corresponding changes in GFR and fractional
      excretion of Li(+) suggest that altered proximal tubular reabsorption after amino
      acids is an early pathophysiologic mechanism. Resistance to the amino acid
      translocating actions of insulin may play a role in the biological response to
      amino acids in this setting. This glomerular reserve phenotype may be useful in
      genetic studies of renal traits preceding or predisposing to hypertension.

PMID- 11244017
TI  - Determinants of spontaneous baroreflex sensitivity in a healthy working
      population.
AB  - Baroreflex sensitivity (BRS) by the spontaneous sequence technique has been
      widely used as a cardiac autonomic index for a variety of pathological
      conditions. However, little information is available on determinants of the
      variability of spontaneous BRS and on age-related reference values of this
      measurement in a healthy population. We evaluated BRS as the slope of spontaneous
      changes in systolic blood pressure (BP) and pulse interval from 10 minutes BP
      (Finapres) and ECG recordings in 1134 healthy volunteers 18 to 60 years of age.
      Measurement of BRS could be obtained in 90% of subjects. Those with unmeasurable
      spontaneous BRS had a slightly lower heart rate but were otherwise not different
      from the rest of the population. BRS was inversely related to age (lnBRS, 3.24
      0.03xage; r(2)=0.23; P:<0.0001) in both genders. In addition, univariate analysis
      revealed a significant inverse correlation between BRS and heart rate, body mass
      index, and BP. Sedentary lifestyle and regular alcohol consumption were also
      associated with lower BRS. However, only age, heart rate, systolic and diastolic
      BP, body mass index, smoking, and gender were independent predictors of BRS in a
      multivariate model, accounting for 47% of the variance of BRS. The present study
      provides reference values for spontaneous BRS in a healthy white population. Only
      approximately half of the variability of BRS could be explained by anthropometric
      variables and common risk factors, which suggests that a significant proportion
      of interindividual differences may reflect genetic heterogeneity.

PMID- 11244019
TI  - Impaired sodium excretion during mental stress in mild essential hypertension.
AB  - In hypertensive rats, environmental stress causes sodium retention by an
      exaggerated increase in renal sympathetic nerve activity, which is modulated by
      angiotensin II. We tested whether similar effects can be observed in humans. In
      66 normotensive subjects (half of them with a family history of hypertension) and
      36 subjects with mild essential hypertension, urinary sodium excretion and renal
      hemodynamics were examined at rest and during mental stress treated either with
      placebo or ACE inhibition in a double-blind, randomized, cross-over design.
      Despite a marked increase in glomerular filtration rate in response to mental
      stress (Deltaglomerular filtration rate, 4.3+/-7.7 mL/min in normotensives
      without versus 5.6+/-8.4 mL/min in normotensives with a family history versus
      10.1+/-5.7 mL/min in patients with mild essential hypertension; P:<0.002), the
      increase in urinary sodium excretion was blunted in patients with mild essential
      hypertension (Deltaurinary sodium excretion, 0.12+/-0.17 mmol/min versus 0.10+/
      0.14 mmol/min versus 0.05+/-0.14 mmol/min; P:<0.05). ACE inhibition corrected the
      natriuretic response to mental stress in subjects with mild essential
      hypertension (Deltaurinary sodium excretion, 0.05+/-0.14 mmol/min with placebo
      versus 0.13+/-0.19 mmol/min with ACE inhibition; P:<0.01); thus, after ACE
      inhibition, urinary sodium excretion increased similarly in all 3 groups. In
      conclusion, impaired sodium excretion occurs during mental stress in human
      essential hypertension but not in subjects with positive family history of
      hypertension. This abnormality in sodium handling during activation of the
      sympathetic nervous system appears to be mediated by angiotensin II.

PMID- 11244018
TI  - Adenosine, a metabolic trigger of the exercise pressor reflex in humans.
AB  - There is substantial evidence that adenosine activates muscle afferent nerve
      fibers leading to sympathetic stimulation, but the issue remains controversial.
      To further test this hypothesis, we used local injections of adenosine into the
      brachial artery while monitoring systemic muscle sympathetic nerve activity
      (MSNA) with peroneal microneurography. The increase in MSNA induced by 3 mg
      intrabrachial adenosine (106+/-32%) was abolished if forearm afferent traffic was
      interrupted by axillary ganglionic blockade (21+/-19%, n=5, P:<0.05).
      Furthermore, the increase in MSNA induced by intravenous adenosine was 3.7-fold
      lower and later (onset latency 20.9+/-4.8 seconds versus 8.5+/-1 seconds) than
      intrabrachial adenosine. Finally, we used forearm exercise (dynamic handgrip at
      50% and 15% maximal voluntary contraction, MVC), with or without superimposed
      ischemia, to modulate interstitial levels of adenosine (estimated with
      microdialysis) while monitoring MSNA. Fifteen minutes of intense (50% MVC) and
      moderate (15% MVC) exercise increased adenosine dialysate concentrations from
      0.31+/-0.1 to 1.24+/-0.4 micromol/L (528+/-292%) and from 0.1+/-0.02 to 0.419+/
      0.16 micromol/L (303+/-99%), respectively (n=7, P:<0.01). MSNA increased 88+/-25%
      and 38+/-28%, respectively. Five minutes of moderate exercise increased adenosine
      from 0.095+/-0.02 to 0.25+/-0.12 micromol/L, and from 0.095+/-0.02 to 0.48+/-0.19
      micromol/L when ischemia was superimposed on exercise (n=7, P:=0.01). The percent
      increase in MSNA induced by the various interventions correlated with the percent
      increase in dialysate adenosine levels (r=0.96). We conclude that adenosine
      activates muscle afferent nerves, triggering reflex sympathetic activation.

PMID- 11244020
TI  - Familial factors of blood pressure and adiposity covariation.
AB  - In the present study, we used the maximum likelihood approach as implemented by
      variance analysis and attempted to quantify genetic and environmental components
      of variance in systolic (SBP) and diastolic (DBP) blood pressure in 514
      individuals who belonged to a total of 135 nuclear families of Chuvasha, Russia,
      ethnic origin. The extent to which these interindividual differences depend on
      age, gender, body mass index (BMI) and other anthropometric measurements was
      investigated. Major findings include the following. (1) The variation in both SBP
      and DBP was significantly affected by genetic factors (h(2)(SBP)=0.51+/-0.13,
      h(2)(DBP)=0.20+/-0.09), shared household environment, and age. These effects were
      stronger with respect to SBP, which also showed significant gender differences in
      baseline values and rate of SBP increase with age. (2) Genetic and common
      household factors, as well as undetected residual effects, were not completely
      independent. The respective 3 facets of correlation between SBP and DBP were
      significant: 0.66+/-0.10, 0.76+/-0.11, and 0.55+/-0.14. (3) SBP and DBP each
      showed significant phenotypic correlations with BMI and anthropometric factors.
      These correlations had a substantial genetic component but were not equal for SBP
      and DBP. SBP showed the highest genetic correlation with arm circumference
      (r(G)=0.63), whereas for DBP, this was found with hip skinfold (r(G=)0.88). (4)
      Bivariate heritability estimates, as well as adjustment of BP measurements for
      BMI and selected anthropometrics, indicated that DBP likely does not have
      independent genetic heritability. The residual genetic variance of adjusted SBP
      remained significant, although substantially lower in comparison with the
      nonadjusted h(2).

PMID- 11244021
TI  - Leptin acts in the central nervous system to produce dose-dependent changes in
      arterial pressure.
AB  - Systemic leptin increases energy expenditure through sympathetic mechanisms,
      decreases appetite, and increases arterial pressure. We tested the hypothesis
      that the pressor action of leptin is mediated by the central nervous system. The
      interaction of dietary salt with leptin was also studied. Leptin was infused for
      2 to 4 weeks into the third cerebral ventricle of Sprague-Dawley rats. Arterial
      pressure was measured by radiotelemetry. To control for the effects of leptin on
      body weight, vehicle-treated rats were pair-fed to the leptin group.
      Intracerebroventricular infusion of leptin at 200 ng/h in salt-depleted rats
      caused a reduction in food intake, weight loss, tachycardia, and decreased
      arterial pressure. Leptin at 1000 ng/h caused further reduction in food intake,
      weight loss, and tachycardia and prevented the hypotensive effect of weight loss
      observed in pair-fed, vehicle-treated animals. Intracerebroventricular leptin at
      1000 ng/h in high-salt-fed rats also caused a sustained pressor response (+3+/-1
      mm Hg), but high-salt intake did not potentiate the pressor effect of leptin.
      Intracerebroventricular leptin potentiated the pressor effect of air-jet stress.
      Intravenous administration of the same dose of leptin (1000 ng/h) did not change
      weight or arterial pressure, suggesting a direct central nervous system action.
      In contrast, a high dose of intravenous leptin (18 000 ng/h) caused weight loss
      and prevented the depressor effect of weight loss. In conclusion, this study
      demonstrates that high-dose leptin increases arterial pressure and heart rate
      through central neural mechanisms but leptin does not enhance salt sensitivity of
      arterial pressure. Leptin appears to oppose the depressor effect of weight loss.

PMID- 11244022
TI  - Restoration of nitric oxide availability after calcium antagonist treatment in
      essential hypertension.
AB  - Essential hypertension is associated with impaired endothelium-dependent
      vasodilation caused by oxygen free radical-induced nitric oxide (NO) breakdown.
      Because calcium antagonists can improve endothelial function in patients with
      essential hypertension, in this study we tested the hypothesis that this
      beneficial effect could be related to restoration of NO availability by
      antioxidant properties. In 15 healthy subjects and 15 hypertensive patients, we
      studied forearm blood flow (strain-gauge plethysmography) modifications induced
      by intrabrachial acetylcholine (ACh; 0.15, 0.45, 1.5, 4.5, and 15 microg/100 mL
      per minute), an endothelium-dependent vasodilator in basal conditions, during
      infusion of N:(G)-monomethyl-L-arginine (L-NMMA, 100 microg/100 mL forearm tissue
      per minute), an NO-synthase inhibitor, vitamin C (8 mg/100 mL forearm tissue per
      minute), and finally, simultaneous infusion of L-NMMA and vitamin C. The response
      to sodium nitroprusside (SNP; 1, 2, and 4 microg/100 mL forearm tissue per
      minute) was also evaluated. In control subjects, vasodilation to ACh was
      inhibited by L-NMMA and not changed by vitamin C. In hypertensive patients,
      vasodilation to ACh was blunted as compared with control subjects and resistant
      to L-NMMA. Vitamin C, which decreased plasma isoprostanes and increased plasma
      antioxidant capacity, increased the response to ACh and restored the inhibiting
      effect of L-NMMA. In hypertensive patients, the study was repeated after 3-month
      treatment with nifedipine gastrointestinal therapeutic system (30 to 60
      mg/daily). Nifedipine treatment decreased circulating plasma lipoperoxides and
      isoprostanes and increased plasma antioxidant capacity. Moreover, nifedipine
      increased the vasodilation to ACh but not to SNP and restored the inhibiting
      effect of L-NMMA on ACh-induced vasodilation, whereas vitamin C no longer exerted
      its facilitating activity. These results indicate that nifedipine increases
      endothelium-dependent vasodilation by restoring NO availability, an effect
      probably determined by antioxidant activity.

PMID- 11244023
TI  - Ascorbic acid-induced modulation of venous tone in humans.
AB  - Ascorbic acid appears to have vasodilatory properties, but the underlying
      mechanisms are not well understood. The aims of this study were to define the
      acute effects of locally infused ascorbic acid in human veins and to explore
      underlying mechanisms by using pharmacological tools in vivo. Ascorbic acid was
      infused in dorsal hand veins submaximally preconstricted with the alpha(1)
      adrenoceptor agonist phenylephrine or with prostaglandin F(2alpha) in 23 healthy
      male nonsmokers, and the venodilator response was measured. Ascorbic acid
      produced dose-dependent dilation with maximum reversal of constriction of 38+/-4%
      in phenylephrine-preconstricted veins and of 51+/-13% in prostaglandin F(2alpha)
      preconstricted veins. Oral pretreatment with the cyclooxygenase inhibitor
      acetylsalicylic acid or local coinfusion of ascorbic acid and the nitric oxide
      synthase inhibitor N:(G)-monomethyl-L-arginine had no effect, but coinfusion of
      ascorbic acid and methylene blue (to inhibit cGMP generation) abolished
      venodilation. Coinfusion of ascorbic acid and the nonselective potassium channel
      blocker quinidine abolished venodilation, whereas the inhibitor of ATP-dependent
      potassium channels glibenclamide had no effect. In cultured bovine endothelial
      cells, ascorbic acid did not affect intracellular calcium concentration but
      blunted the response to ATP or digitonin exposure. Ascorbic acid, in millimolar
      concentrations, dilates human hand veins, presumably by activation of vascular
      smooth muscle potassium channels through cGMP. This activation is independent of
      eNOS-mediated nitric oxide synthesis and cyclooxygenase products and does not
      involve ATP-dependent potassium channels.

PMID- 11244024
TI  - Src tyrosine kinases and extracellular signal-regulated kinase 1/2 mitogen
      activated protein kinases mediate pressure-induced c-fos expression in cannulated
      rat mesenteric small arteries.
AB  - Chronic hypertension is associated with remodeling of small arteries. There is
      evidence that the high pressure itself may cause these structural changes, but
      the responsible mechanisms are not clearly defined. Previously we showed that
      pressure-induced c-fos expression in intact cannulated rat mesenteric small
      arteries was inhibited by genistein, a general tyrosine kinase inhibitor. The
      purpose of this study was to further unravel the underlying signal transduction
      mechanisms, and we particularly tested the involvement of src tyrosine kinases
      and extracellular signal-regulated kinase (ERK). Rat mesenteric small arteries
      were cannulated in a dual-vessel chamber. After a 60-minute equilibration period,
      the pressure in 1 artery was increased to 140 mm Hg, while the other artery
      remained at 90 mm Hg. Semiquantitative reverse transcriptase-polymerase chain
      reaction was used to determine c-fos expression, and Western blotting was used to
      examine levels of ERK phosphorylation. The involvement of src and ERK was tested
      with the inhibitors herbimycin A (1 micromol/L), PP1 (10 micromol/L), PP2 (10
      micromol/L), and PD98059 (30 micromol/L). One-hour exposure to 140 mm Hg
      increased the c-fos/cyclophilin ratio 3.6-fold, from 0.29+/-0.07 to 1.06+/-0.25.
      All the tested inhibitors suppressed the pressure-induced increase of c-fos
      expression. A 5-minute exposure period to 140 mm Hg increased ERK
      phosphorylation, and this was abolished in the presence of PP1. The results
      suggest that pressure-induced c-fos expression in intact cannulated rat
      mesenteric small arteries may be mediated, at least in part, by src tyrosine
      kinases and ERK.

PMID- 11244025
TI  - Effect of valsartan on angiotensin II-induced plasminogen activator inhibitor-1
      biosynthesis in arterial smooth muscle cells.
AB  - Previous studies have shown that angiotensin II stimulates the synthesis of
      plasminogen activator inhibitor-1 in cultured vascular cells, which suggests that
      activation of the renin-angiotensin system may impair fibrinolysis. We have
      investigated the effects of angiotensin II and of valsartan, a recently developed
      angiotensin II antagonist that is highly specific and selective for the
      angiotensin II subtype 1 receptor, on plasminogen activator inhibitor-1 secretion
      by smooth muscle cells isolated from rat and human vessels. Angiotensin II
      induced a time- and concentration-dependent increase of plasminogen activator
      inhibitor activity in supernatants of rat aortic cells, which reached a plateau
      after 6 hours of incubation with 100 nmol/L angiotensin II (2.4+/-0.6-fold over
      control value; P:<0.001). The angiotensin II-induced plasminogen activator
      inhibitor activity was inhibited, in a concentration-dependent manner, by
      valsartan with an IC(50) value of 21 nmol/L. Valsartan fully prevented the
      angiotensin II-induced increase in plasminogen activator inhibitor-1 protein and
      mRNA. Furthermore, angiotensin II doubled the secretion of plasminogen activator
      inhibitor-1 by smooth muscle cells obtained from human umbilical and internal
      mammary arteries, and valsartan fully prevented it. Angiotensin II did not affect
      the secretion of tissue plasminogen activator antigen by any of the cell systems
      tested. Thus, valsartan effectively inhibits angiotensin II-induced plasminogen
      activator inhibitor-1 secretion without affecting that of tissue plasminogen
      activator in arterial rat and human smooth muscle cells.

PMID- 11244026
TI  - Effects of angiotensin-converting enzyme inhibitor and angiotensin type 1
      receptor antagonist in deoxycorticosterone acetate-salt hypertensive mice lacking
      Ren-2 gene.
AB  - We previously reported that inhibition of angiotensin-converting enzyme (ACE)
      prevented the hypertension and left ventricular hypertrophy induced by
      deoxycorticosterone acetate-salt (DOCA-salt) in 129/SvEvTac mice, which have 2
      renin genes (Ren-1 and Ren-2). In the present study, we induced hypertension by
      uninephrectomy and DOCA-salt in mice having only the Ren-1 gene (C57BL/6J) and
      investigated the effect of an ACE inhibitor (ramipril, 4 mg. kg(-)(1). d(-)(1))
      and an angiotensin type 1 (AT(1)) receptor antagonist (L-158809, 4 mg. kg(-)(1).
      d(-)(1)) on the development of hypertension, cardiac hypertrophy, and renal
      injury. After 4 weeks of treatment, systolic blood pressure in DOCA-salt mice was
      significantly increased (128+/-2 mm Hg) compared with controls (109+/-2 mm Hg)
      (P:<0.001), while plasma renin concentration was decreased by 97% (P:<0.001).
      DOCA-salt also induced left ventricular and renal hypertrophy and renal damage as
      manifested by proteinuria. Collagen content in the left ventricle and kidney was
      significantly higher in DOCA-salt mice (P:<0.001). Urinary albumin (P:<0.05) and
      proliferating cell nucleic antigen-positive cells in the tubules and interstitium
      of the renal cortex (P:<0.001) were significantly increased in the DOCA-salt
      group. Neither the ACE inhibitor nor the AT(1) antagonist had any
      antihypertensive effect; however, they partially prevented cardiac hypertrophy
      and completely inhibited left ventricular collagen deposition. In the kidney,
      both the ACE inhibitor and AT(1) antagonist partially reduced the increase in
      collagen but had no effect on hypertrophy. They also significantly prevented the
      effect of DOCA-salt on urinary albumin and proliferating cell nucleic antigen
      expression in the kidney. Despite the lack of an antihypertensive effect, both
      ACE inhibitor and AT(1) antagonist prevented cardiac remodeling and renal damage.
      Our results indicate that ACE inhibitors and AT(1) antagonists exert beneficial
      effects on the heart and kidney in DOCA-salt hypertensive mice independently of
      their effects on blood pressure.

PMID- 11244027
TI  - Prevention of hypertension by irbesartan in Dahl S rats relates to central
      angiotensin II type 1 receptor blockade.
AB  - Hypertension in Dahl S rats on high-salt intake is in general considered a model
      of "low-renin hypertension," unresponsive to treatment with blockers of the renin
      angiotensin system. However, direct central administration of an angiotensin II
      type 1 (AT(1)) receptor blocker prevents both the sympathoexcitation and
      hypertension caused by high-salt intake in Dahl S rats. In the present study, we
      tested the hypothesis that chronic peripheral administration of an AT(1) receptor
      blocker inhibits the salt-induced hypertension relative to the extent of central
      AT(1) receptor blockade that is induced. Dahl S rats received a high-salt (1370
      micromol Na(+)/g) or regular (101 micromol Na(+)/g) diet from 4 to 8 weeks of
      age. In 3 different sets of experiments, Dahl S on high salt were randomized to
      intracerebroventricular (ICV) treatment with control infusion versus irbesartan
      at 50 or 250 microg. kg(-1). d(-1), oral treatment with control versus irbesartan
      at 125 or 500 mg. kg(-1). d(-1) once daily by gavage, or subcutaneous treatment
      with control versus irbesartan at 50 or 150 mg. kg(-1). d(-1) by once daily
      injection. At 8 weeks of age, MAP was measured in conscious rats at rest and in
      response to angiotensin II ICV or IV. On high-salt intake, Dahl S developed the
      anticipated marked increase in MAP to approximately 160 mm Hg. Irbesartan ICV did
      not affect pressor responses to angiotensin II IV, but irbesartan administered
      subcutaneously or by gavage markedly inhibited these responses. Irbesartan ICV or
      by gavage partially inhibited pressor responses to angiotensin II ICV and the
      development of hypertension. Irbesartan subcutaneously at the higher dose more
      completely inhibited pressor responses to angiotensin II ICV and fully prevented
      the salt-induced hypertension. The degree of central but not peripheral AT(1)
      receptor blockade parallels the antihypertensive effect of irbesartan, indicating
      that inhibition of the brain renin-angiotensin system can contribute to a
      significant extent to the therapeutic effectiveness of AT(1) receptor blockers
      such as irbesartan when administered in sufficiently high doses to cause central
      AT(1) receptor blockade.

PMID- 11244028
TI  - Specificity and degeneracy in antigen recognition: yin and yang in the immune
      system.
AB  - One of the hallmarks of the immune system is specificity, a concept based on
      innumerable observations that antibodies react with the substance that elicited
      their production and only a few other structurally similar substances. The study
      of T cells has begun to suggest, however, that in responses mediated by their
      antibody-like receptors (T cell receptor or TCR) an individual T cell, expressing
      a singular TCR, can discriminate as exquisitely among antigens as the most
      specific antibodies but also exhibit "degeneracy": i.e., it can react with many
      disparate antigens (peptide-MHC complexes). An explanation for this duality
      (specificity and degeneracy) can be found in (i) the powerful amplifying signal
      transduction cascades that allow a T cell to respond to the stable engagement of
      very few TCR molecules, initially perhaps only one or two out of around 100,000
      per cell, by their natural ligands (peptide-MHC complexes or epitopes on antigen
      presenting cells--or APC) and (ii) the inverse relationship between TCR affinity
      for epitopes and epitope density (the number of copies of an epitope per APC).
      Older observations on the excess of total globulin production over specific
      antibody production in response to conventional immunization procedures suggest
      that B cells also exhibit degeneracy, as well as specificity. These views are
      developed against a backdrop describing how the author became interested in the
      immune system and has pursued that interest. "...a concept of science drawn from
      ...is [textbooks]...is no more likely to fit the enterprise that produced them
      than an image of a national culture drawn from a tourist brochure." Thomas Kuhn,
      Structure Of Scientific Revolutions

PMID- 11244029
TI  - In vivo activation of antigen-specific CD4 T cells.
AB  - Physical detection of antigen-specific CD4 T cells has revealed features of the
      in vivo immune response that were not appreciated from in vitro studies. In vivo,
      antigen is initially presented to naive CD4 T cells exclusively by dendritic
      cells within the T cell areas of secondary lymphoid tissues. Anatomic constraints
      make it likely that these dendritic cells acquire the antigen at the site where
      it enters the body. Inflammation enhances in vivo T cell activation by
      stimulating dendritic cells to migrate to the T cell areas and display stable
      peptide-MHC complexes and costimulatory ligands. Once stimulated by a dendritic
      cell, antigen-specific CD4 T cells produce IL-2 but proliferate in an IL-2-
      independent fashion. Inflammatory signals induce chemokine receptors on activated
      T cells that direct their migration into the B cell areas to interact with
      antigen-specific B cells. Most of the activated T cells then die within the
      lymphoid tissues. However, in the presence of inflammation, a population of
      memory T cells survives. This population is composed of two functional classes.
      One recirculates through nonlymphoid tissues and is capable of immediate effector
      lymphokine production. The other recirculates through lymph nodes and quickly
      acquires the capacity to produce effector lymphokines if stimulated. Therefore,
      antigenic stimulation in the presence of inflammation produces an increased
      number of specific T cells capable of producing effector lymphokines throughout
      the body.

PMID- 11244030
TI  - Cross-presentation, dendritic cells, tolerance and immunity.
AB  - This review examines the role of cross-presentation in tolerance and immunity. We
      discuss (a) the antigenic requirements for cross-presentation, (b) the phenotype
      of the antigen presenting cell (APC), (c) the cellular interactions and molecular
      signals involved in cross-priming, and (d) the factors that direct the immune
      system toward tolerance or immunity. A large part of this review is dedicated to
      summarizing our current knowledge of the cross-presenting APC.

PMID- 11244031
TI  - Noncytolytic control of viral infections by the innate and adaptive immune
      response.
AB  - This review describes the contribution of noncytolytic mechanisms to the control
      of viral infections with a particular emphasis on the role of cytokines in these
      processes. It has long been known that most cell types in the body respond to an
      incoming viral infection by rapidly secreting antiviral cytokines such as
      interferon alpha/beta (IFN-alpha/beta). After binding to specific receptors on
      the surface of infected cells, IFN-alpha/beta has the potential to trigger the
      activation of multiple noncytolytic intracellular antiviral pathways that can
      target many steps in the viral life cycle, thereby limiting the amplification and
      spread of the virus and attenuating the infection. Clearance of established viral
      infections, however, requires additional functions of the immune response. The
      accepted dogma is that complete clearance of intracellular viruses by the immune
      response depends on the destruction of infected cells by the effector cells of
      the innate and adaptive immune system [natural killer (NK) cells and cytotoxic T
      cells (CTLs)]. This notion, however, has been recently challenged by experimental
      evidence showing that much of the antiviral potential of these cells reflects
      their ability to produce antiviral cytokines such as IFN-gamma and tumor necrosis
      factor (TNF)-alpha at the site of the infection. Indeed, these cytokines can
      purge viruses from infected cells noncytopathically as long as the cell is able
      to activate antiviral mechanisms and the virus is sensitive to them. Importantly,
      the same cytokines also control viral infections indirectly, by modulating the
      induction, amplification, recruitment, and effector functions of the immune
      response and by upregulating antigen processing and display of viral epitopes at
      the surface of infected cells. In keeping with these concepts, it is not
      surprising that a number of viruses encode proteins that have the potential to
      inhibit the antiviral activity of cytokines.

PMID- 11244032
TI  - Immunology of tuberculosis.
AB  - The resurgence of tuberculosis worldwide has intensified research efforts
      directed at examining the host defense and pathogenic mechanisms operative in
      Mycobacterium tuberculosis infection. This review summarizes our current
      understanding of the host immune response, with emphasis on the roles of
      macrophages, T cells, and the cytokine/chemokine network in engendering
      protective immunity. Specifically, we summarize studies addressing the ability of
      the organism to survive within macrophages by controlling phagolysosome fusion.
      The recent studies on Toll-like receptors and the impact on the innate response
      to M. tuberculosis are discussed. We also focus on the induction, specificity,
      and effector functions of CD4(+) and CD8(+) T cells, and the roles of cytokines
      and chemokines in the induction and effector functions of the immune response.
      Presentation of mycobacterial antigens by MHC class I, class II, and CD1 as well
      as the implications of these molecules sampling various compartments of the cell
      for presentation to T cells are discussed. Increased attention to this disease
      and the integration of animal models and human studies have afforded us a greater
      understanding of tuberculosis and the steps necessary to combat this infection.
      The pace of this research must be maintained if we are to realize an effective
      vaccine in the next decades.

PMID- 11244033
TI  - Tolerance to islet autoantigens in type 1 diabetes.
AB  - Tolerance to beta cell autoantigens represents a fragile equilibrium.
      Autoreactive T cells specific to these autoantigens are present in most normal
      individuals but are kept under control by a number of peripheral tolerance
      mechanisms, among which CD4(+) CD25(+) CD62L(+) T cell-mediated regulation
      probably plays a central role. The equilibrium may be disrupted by inappropriate
      activation of autoantigen-specific T cells, notably following to local
      inflammation that enhances the expression of the various molecules contributing
      to antigen recognition by T cells. Even when T cell activation finally overrides
      regulation, stimulation of regulatory cells by CD3 antibodies may reset the
      control of autoimmunity. Other procedures may also lead to disease prevention.
      These procedures are essentially focused on Th2 cytokines, whether used
      systemically or produced by Th2 cells after specific stimulation by autoantigens.
      Protection can also be obtained by NK T cell stimulation. Administration of beta
      cell antigens or CD3 antibodies is now being tested in clinical trials in
      prediabetics and/or recently diagnosed diabetes.

PMID- 11244034
TI  - Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned?
AB  - Rheumatoid arthritis (RA), a systemic disease, is characterized by a chronic
      inflammatory reaction in the synovium of joints and is associated with
      degeneration of cartilage and erosion of juxta-articular bone. Many pro
      inflammatory cytokines including TNF alpha, chemokines, and growth factors are
      expressed in diseased joints. The rationale that TNF alpha played a central role
      in regulating these molecules, and their pathophysiological potential, was
      initially provided by the demonstration that anti-TNF alpha antibodies added to
      in vitro cultures of a representative population of cells derived from diseased
      joints inhibited the spontaneous production of IL-1 and other pro-inflammatory
      cytokines. Systemic administration of anti-TNF alpha antibody or sTNFR fusion
      protein to mouse models of RA was shown to be anti-inflammatory and joint
      protective. Clinical investigations in which the activity of TNF alpha in RA
      patients was blocked with intravenously administered infliximab, a chimeric anti
      TNF alpha monoclonal antibody (mAB), has provided evidence that TNF regulates IL
      6, IL-8, MCP-1, and VEGF production, recruitment of immune and inflammatory cells
      into joints, angiogenesis, and reduction of blood levels of matrix
      metalloproteinases-1 and -3. Randomized, placebo-controlled, multi-center
      clinical trials of human TNF alpha inhibitors have demonstrated their consistent
      and remarkable efficacy in controlling signs and symptoms, with a favorable
      safety profile, in approximately two thirds of patients for up to 2 years, and
      their ability to retard joint damage. Infliximab (a mAB), and etanercept (a sTNF
      R-Fc fusion protein) have been approved by regulatory authorities in the United
      States and Europe for treating RA, and they represent a significant new addition
      to available therapeutic options.

PMID- 11244035
TI  - Activating receptors and coreceptors involved in human natural killer cell
      mediated cytolysis.
AB  - Natural killer cells can discriminate between normal cells and cells that do not
      express adequate amounts of major histocompatibility complex (MHC) class I
      molecules. The discovery, both in mouse and in human, of MHC-specific inhibitory
      receptors clarified the molecular basis of this important NK cell function.
      However, the triggering receptors responsible for positive NK cell stimulation
      remained elusive until recently. Some of these receptors have now been identified
      in humans, thus shedding some light on the molecular mechanisms involved in NK
      cell activation during the process of natural cytotoxicity. Three novel, NK
      specific, triggering surface molecules (NKp46, NKp30, and NKp44) have been
      identified. They represent the first members of a novel emerging group of
      receptors collectively termed natural cytotoxicity receptors (NCR). Monoclonal
      antibodies (mAbs) to NCR block to differing extents the NK-mediated lysis of
      various tumors. Moreover, lysis of certain tumors can be virtually abrogated by
      the simultaneous masking of the three NCRs. There is a coordinated surface
      expression of the three NCRs, their surface density varying in different
      individuals and also in the NK cells isolated from a given individual. A direct
      correlation exists between the surface density of NCR and the ability of NK cells
      to kill various tumors. NKp46 is the only NCR involved in human NK-mediated
      killing of murine target cells. Accordingly, a homologue of NKp46 has been
      detected in mouse. Molecular cloning of NCR revealed novel members of the Ig
      superfamily displaying a low degree of similarity to each other and to known
      human molecules. NCRs are coupled to different signal transducing adaptor
      proteins, including CD3 zeta, Fc epsilon RI gamma, and KARAP/DAP12. Another
      triggering NK receptor is NKG2D. It appears to play either a complementary or a
      synergistic role with NCRs. Thus, the triggering of NK cells in the process of
      tumor cell lysis may often depend on the concerted action of NCR and NKG2D. In
      some instances, however, it may uniquely depend upon the activity of NCR or NKG2D
      only. Strict NKG2D-dependency can be appreciated using clones that, in spite of
      their NCR(dull) phenotype, efficiently lyse certain epithelial tumors or leukemic
      cell lines. Other triggering surface molecules including 2B4 and the novel NKp80
      appear to function as coreceptors rather than as true receptors. Indeed, they can
      induce natural cytotoxicity only when co-engaged with a triggering receptor.
      While an altered expression or function of NCR or NKG2D is being explored as a
      possible cause of immunological disorders, 2B4 dysfunction has already been
      associated with a severe form of immunodeficiency. Indeed, in patients with the X
      linked lymphoproliferative disease, the inability to control Epstein-Barr virus
      infections may be consequent to a major dysfunction of 2B4 that exerts inhibitory
      instead of activating functions.

PMID- 11244036
TI  - Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and
      transplantation.
AB  - Recent advances in the understanding of T cell activation have led to new
      therapeutic approaches in the treatment of immunological disorders. One
      attractive target of intervention has been the blockade of T cell costimulatory
      pathways, which result in more selective effects on only those T cells that have
      encountered specific antigen. In fact, in some instances, costimulatory pathway
      antagonists can induce antigen-specific tolerance that prevents the progression
      of autoimmune diseases and organ graft rejection. In this review, we summarize
      the current understanding of these complex costimulatory pathways including the
      individual roles of the CD28, CTLA-4, B7-1 (CD80), and B7-2 (CD86) molecules. We
      present evidence that suggests that multiple mechanisms contribute to CD28/B7
      mediated T cell costimulation in disease settings that include expansion of
      activated pathogenic T cells, differentiation of Th1/Th2 cells, and the migration
      of T cells into target tissues. Additionally, the negative regulatory role of
      CTLA-4 in autoimmune diseases and graft rejection supports a dynamic but complex
      process of immune regulation that is prominent in the control of self-reactivity.
      This is most apparent in regulation of the CD4(+)CD25(+)CTLA-4(+)
      immunoregulatory T cells that control multiple autoimmune diseases. The
      implications of these complexities and the potential for use of these therapies
      in clinical immune intervention are discussed.

PMID- 11244037
TI  - gp120: Biologic aspects of structural features.
AB  - HIV-1 particles are decorated with a network of densely arranged envelope spikes
      on their surface. Each spike is formed of a trimer of heterodimers of the gp120
      surface and the gp41 transmembrane glycoproteins. These molecules mediate HIV-1
      entry into target cells, initiating the HIV-1 replication cycle. They are a
      target for entry-blocking drugs and for neutralizing Abs that could contribute to
      vaccine protection. The crystal structure of the core of gp120 has been recently
      solved. It reveals the structure of the conserved HIV-1 receptor binding sites
      and some of the mechanisms evolved by HIV-1 to escape Ab responses. The gp120
      consists of three faces. One is largely inaccessible on the native trimer, and
      two faces are exposed but apparently have low immunogenicity, particularly on
      primary viruses. We have modeled HIV-1 neutralization by a CD4 binding site
      monoclonal Ab, and we propose that neutralization takes place by inhibition of
      the interaction between gp120 and the target cell membrane receptors as a result
      of steric hindrance. Knowledge of gp120 structure and function should assist in
      the design of new drugs as well as of an effective vaccine. In the latter case,
      circumventing the low immunogenicity of the HIV-1 envelope spike is a major
      challenge.

PMID- 11244038
TI  - IgG Fc receptors.
AB  - Since the description of the first mouse knockout for an IgG Fc receptor seven
      years ago, considerable progress has been made in defining the in vivo functions
      of these receptors in diverse biological systems. The role of activating Fc gamma
      Rs in providing a critical link between ligands and effector cells in type II and
      type III inflammation is now well established and has led to a fundamental
      revision of the significance of these receptors in initiating cellular responses
      in host defense, in determining the efficacy of therapeutic antibodies, and in
      pathological autoimmune conditions. Considerable progress has been made in the
      last two years on the in vivo regulation of these responses, through the
      appreciation of the importance of balancing activation responses with inhibitory
      signaling. The inhibitory FcR functions in the maintenance of peripheral
      tolerance, in regulating the threshold of activation responses, and ultimately in
      terminating IgG mediated effector stimulation. The consequences of deleting the
      inhibitory arm of this system are thus manifested in both the afferent and
      efferent immune responses. The hyperresponsive state that results leads to
      greatly magnified effector responses by cytotoxic antibodies and immune complexes
      and can culminate in autoimmunity and autoimmune disease when modified by
      environmental or genetic factors. Fc gamma Rs offer a paradigm for the biological
      significance of balancing activation and inhibitory signaling in the expanding
      family of activation/inhibitory receptor pairs found in the immune system.

PMID- 11244039
TI  - Regulation of the natural killer cell receptor repertoire.
AB  - Natural killer cells express inhibitory receptors specific for MHC class I
      proteins and stimulatory receptors with diverse specificities. The MHC-specific
      receptors discriminate among different MHC class I alleles and are expressed in a
      variegated, overlapping fashion, such that each NK cell expresses several
      inhibitory and stimulatory receptors. Evidence suggests that individual
      developing NK cells initiate expression of inhibitory receptor genes in a
      sequential, cumulative, and stochastic fashion. Superimposed on the receptor
      acquisition process are multiple education mechanisms, which act to coordinate
      the stimulatory and inhibitory specificities of developing NK cells. One process
      influences the complement of receptors expressed by individual NK cells. Other
      mechanisms may prevent NK cell autoaggression even when the developing NK cell
      fails to express self-MHC-specific inhibitory receptors. Together, these
      mechanisms ensure a self-tolerant and maximally discriminating NK cell
      population. Like NK cells, a fraction of memory phenotype CD8(+) T cells, as well
      as other T cell subsets, express inhibitory class I--specific receptors in a
      variegated, overlapping fashion. The characteristics of these cells suggest that
      inhibitory receptor expression may be a response to prior antigenic stimulation
      as well as to poorly defined additional signals. A unifying hypothesis is that
      both NK cells and certain T cell subsets initiate expression of inhibitory
      receptors in response to stimulation.

PMID- 11244040
TI  - The bare lymphocyte syndrome and the regulation of MHC expression.
AB  - The bare lymphocyte syndrome (BLS) is a hereditary immunodeficiency resulting
      from the absence of major histocompatibility complex class II (MHCII) expression.
      Considering the central role of MHCII molecules in the development and activation
      of CD4(+) T cells, it is not surprising that the immune system of the patients is
      severely impaired. BLS is the prototype of a "disease of gene regulation." The
      affected genes encode RFXANK, RFX5, RFXAP, and CIITA, four regulatory factors
      that are highly specific and essential for MHCII genes. The first three are
      subunits of RFX, a trimeric complex that binds to all MHCII promoters. CIITA is a
      non-DNA-binding coactivator that functions as the master control factor for MHCII
      expression. The study of RFX and CIITA has made major contributions to our
      comprehension of the molecular mechanisms controlling MHCII genes and has made
      this system into a textbook model for the regulation of gene expression.

PMID- 11244041
TI  - The immunological synapse.
AB  - The adaptive immune response is initiated by the interaction of T cell antigen
      receptors with major histocompatibility complex molecule-peptide complexes in the
      nanometer scale gap between a T cell and an antigen-presenting cell, referred to
      as an immunological synapse. In this review we focus on the concept of
      immunological synapse formation as it relates to membrane structure, T cell
      polarity, signaling pathways, and the antigen-presenting cell. Membrane domains
      provide an organizational principle for compartmentalization within the
      immunological synapse. T cell polarization by chemokines increases T cell
      sensitivity to antigen. The current model is that signaling and formation of the
      immunological synapse are tightly interwoven in mature T cells. We also extend
      this model to natural killer cell activation, where the inhibitory NK synapse
      provides a striking example in which inhibition of signaling leaves the synapse
      in its nascent, inverted state. The APC may also play an active role in
      immunological synapse formation, particularly for activation of naive T cells.

PMID- 11244042
TI  - Chemokine signaling and functional responses: the role of receptor dimerization
      and TK pathway activation.
AB  - A broad array of biological responses, including cell polarization, movement,
      immune and inflammatory responses, and prevention of HIV-1 infection, are
      triggered by the chemokines, a family of structurally related chemoattractant
      proteins that bind to specific seven-transmembrane receptors linked to G
      proteins. Here we discuss one of the early signaling pathways activated by
      chemokines, the JAK/STAT pathway. Through this pathway, and possibly in
      conjunction with other signaling pathways, the chemokines promote changes in
      cellular morphology, collectively known as polarization, required for chemotactic
      responses. The polarized cell expresses the chemokine receptors at the leading
      cell edge, to which they are conveyed by rafts, a cholesterol-enriched membrane
      fraction fundamental to the lateral organization of the plasma membrane. Finally,
      the mechanisms through which the chemokines promote their effect are discussed in
      the context of the prevention of HIV-1 infection.

PMID- 11244043
TI  - Interleukin-18 regulates both Th1 and Th2 responses.
AB  - Although interleukin-18 is structurally homologous to IL-1 and its receptor
      belongs to the IL-1R/Toll-like receptor (TLR) superfamily, its function is quite
      different from that of IL-1. IL-18 is produced not only by types of immune cells
      but also by non-immune cells. In collaboration with IL-12, IL-18 stimulates Th1
      mediated immune responses, which play a critical role in the host defense against
      infection with intracellular microbes through the induction of IFN-gamma.
      However, the overproduction of IL-12 and IL-18 induces severe inflammatory
      disorders, suggesting that IL-18 is a potent proinflammatory cytokine that has
      pathophysiological roles in several inflammatory conditions. IL-18 mRNA is
      expressed in a wide range of cells including Kupffer cells, macrophages, T cells,
      B cells, dendritic cells, osteoblasts, keratinocytes, astrocytes, and microglia.
      Thus, the pathophysiological role of IL-18 has been extensively tested in the
      organs that contain these cells. Somewhat surprisingly, IL-18 alone can stimulate
      Th2 cytokine production as well as allergic inflammation. Therefore, the
      functions of IL-18 in vivo are very heterogeneous and complicated. In principle,
      IL-18 enhances the IL-12-driven Th1 immune responses, but it can also stimulate
      Th2 immune responses in the absence of IL-12.

PMID- 11244044
TI  - Multiple viral strategies of HTLV-1 for dysregulation of cell growth control.
AB  - The human T cell leukemia virus-1 (HTLV-1) is a retrovirus that causes adult T
      cell leukemia (ATL) and neurological disorder, the tropical spastic paraparesis
      (HAM/TSP). The pathogenesis apparently results from the pleiotropic function of
      Tax protein, which is a key regulator of viral replication. Tax exerts (a) trans
      activation and -repression of transcription of different sets of cellular genes
      through binding to groups of transcription factors and coactivators, (b)
      dysregulation of cell cycle through binding to inhibitors of CDK4/6, and (c)
      inhibition of some tumor suppressor proteins. These effects on a wide variety of
      cellular targets seem to cooperate in promoting cell proliferation. This is an
      effective viral strategy to amplify its proviral genome through replication of
      infected cells; ultimately it results in cell transformation and leukemogenesis.

PMID- 11244045
TI  - Calcium signaling mechanisms in T lymphocytes.
AB  - Elevation of intracellular free Ca(2+) is one of the key triggering signals for T
      cell activation by antigen. A remarkable variety of Ca(2+) signals in T cells,
      ranging from infrequent spikes to sustained oscillations and plateaus, derives
      from the interactions of multiple Ca(2+) sources and sinks in the cell. Following
      engagement of the T cell receptor, intracellular channels (IP3 and ryanodine
      receptors) release Ca(2+) from intracellular stores, and by depleting the stores
      trigger prolonged Ca(2+) influx through store-operated Ca(2+) (CRAC) channels in
      the plasma membrane. The amplitude and dynamics of the Ca(2+) signal are shaped
      by several mechanisms, including K(+) channels and membrane potential, slow
      modulation of the plasma membrane Ca(2+)-ATPase, and mitochondria that buffer
      Ca(2+) and prevent the inactivation of CRAC channels. Ca(2+) signals have a
      number of downstream targets occurring on multiple time scales. At short times,
      Ca(2+) signals help to stabilize contacts between T cells and antigen-presenting
      cells through changes in motility and cytoskeletal reorganization. Over periods
      of minutes to hours, the amplitude, duration, and kinetic signature of Ca(2+)
      signals increase the efficiency and specificity of gene activation events. The
      complexity of Ca(2+) signals contains a wealth of information that may help to
      instruct lymphocytes to choose between alternate fates in response to antigenic
      stimulation.

PMID- 11244046
TI  - The design of vaccines against Helicobacter pylori and their development.
AB  - Helicobacter pylori is a gram negative, spiral, microaerophylic bacterium that
      infects the stomach of more than 50% of the human population worldwide. It is
      mostly acquired during childhood and, if not treated, persists chronically,
      causing chronic gastritis, peptic ulcer disease, and in some individuals, gastric
      adenocarcinoma and gastric B cell lymphoma. The current therapy, based on the use
      of a proton-pump inhibitor and antibiotics, is efficacious but faces problems
      such as patient compliance, antibiotic resistance, and possible recurrence of
      infection. The development of an efficacious vaccine against H. pylori would thus
      offer several advantages. Various approaches have been followed in the
      development of vaccines against H. pylori, most of which have been based on the
      use of selected antigens known to be involved in the pathogenesis of the
      infection, such as urease, the vacuolating cytotoxin (VacA), the cytotoxin
      associated antigen (CagA), the neutrophil-activating protein (NAP), and others,
      and intended to confer protection prophylactically and/or therapeutically in
      animal models of infection. However, very little is known of the natural history
      of H. pylori infection and of the kinetics of the induced immune responses.
      Several lines of evidence suggest that H. pylori infection is accompanied by a
      pronounced Th1-type CD4(+) T cell response. It appears, however, that after
      immunization, the antigen-specific response is predominantly polarized toward a
      Th2-type response, with production of cytokines that can inhibit the activation
      of Th1 cells and of macrophages, and the production of proinflammatory cytokines.
      The exact effector mechanisms of protection induced after immunization are still
      poorly understood. The next couple of years will be crucial for the development
      of vaccines against H. pylori. Several trials are foreseen in humans, and
      expectations are that most of the questions being asked now on the host-microbe
      interactions will be answered.

PMID- 11244047
TI  - CTLA-4-mediated inhibition in regulation of T cell responses: mechanisms and
      manipulation in tumor immunotherapy.
AB  - The T cell compartment of adaptive immunity provides vertebrates with the
      potential to survey for and respond specifically to an incredible diversity of
      antigens. The T cell repertoire must be carefully regulated to prevent unwanted
      responses to self. In the periphery, one important level of regulation is the
      action of costimulatory signals in concert with T cell antigen-receptor (TCR)
      signals to promote full T cell activation. The past few years have revealed that
      costimulation is quite complex, involving an integration of activating signals
      and inhibitory signals from CD28 and CTLA-4 molecules, respectively, with TCR
      signals to determine the outcome of a T cell's encounter with antigen. Newly
      emerging data suggest that inhibitory signals mediated by CTLA-4 not only can
      determine whether T cells become activated, but also can play a role in
      regulating the clonal representation in a polyclonal response. This review
      primarily focuses on the cellular and molecular mechanisms of regulation by CTLA
      4 and its manipulation as a strategy for tumor immunotherapy.

PMID- 11244048
TI  - B cell development pathways.
AB  - B cell development is a highly regulated process whereby functional peripheral
      subsets are produced from hematopoietic stem cells, in the fetal liver before
      birth and in the bone marrow afterward. Here we review progress in understanding
      some aspects of this process in the mouse bone marrow, focusing on delineation of
      the earliest stages of commitment, on pre-B cell receptor selection, and B cell
      tolerance during the immature-to-mature B cell transition. Then we note some of
      the distinctions in hematopoiesis and pre-B selection between fetal liver and
      adult bone marrow, drawing a connection from fetal development to B-1/CD5(+) B
      cells. Finally, focusing on CD5(+) cells, we consider the forces that influence
      the generation and maintenance of this distinctive peripheral B cell population,
      enriched for natural autoreactive specificities that are encoded by particular
      germline V(H)-V(L) combinations.

PMID- 11244049
TI  - IRF family of transcription factors as regulators of host defense.
AB  - Interferon regulatory factors (IRFs) constitute a family of transcription factors
      that commonly possess a novel helix-turn-helix DNA-binding motif. Following the
      initial identification of two structurally related members, IRF-1 and IRF-2,
      seven additional members have now been reported. In addition, virally encoded
      IRFs, which may interfere with cellular IRFs, have also been identified. Thus
      far, intensive functional analyses have been done on IRF-1, revealing a
      remarkable functional diversity of this transcription factor in the regulation of
      cellular response in host defense. Indeed, IRF-1 selectively modulates different
      sets of genes, depending on the cell type and/or the nature of cellular stimuli,
      in order to evoke appropriate responses in each. More recently, much attention
      has also been focused on other IRF family members. Their functional roles,
      through interactions with their own or other members of the family of
      transcription factors, are becoming clearer in the regulation of host defense,
      such as innate and adaptive immune responses and oncogenesis.

PMID- 11244050
TI  - X-linked lymphoproliferative disease: a progressive immunodeficiency.
AB  - Our understanding of the X-linked lymphoproliferative syndrome (XLP) has advanced
      significantly in the last two years. The gene that is altered in the condition
      (SAP/SH2D1A) has been cloned and its protein crystal structure solved. At least
      two sets of target molecules for this small SH2 domain-containing protein have
      been identified: A family of hematopoietic cell surface receptors, i.e. the SLAM
      family, and a second molecule, which is a phosphorylated adapter. A SAP-like
      protein, EAT-2, has also been found to interact with this family of surface
      receptors. Several lines of evidence, including structural studies and analyses
      of missense mutations in XLP patients, support the notion that SAP/SH2D1A is a
      natural inhibitor of SH2-domain-dependent interactions with members of the SLAM
      family. However, details of its role in signaling mechanisms are yet to be
      unravelled. Further analyses of the SAP/SH2D1A gene in XLP patients have made it
      clear that the development of dys-gammaglobulinemia and B cell lymphoma can occur
      without evidence of prior EBV infection. Moreover, preliminary results of virus
      infections of a mouse in which the SAP/SH2D1A gene has been disrupted suggest
      that EBV infection is not per se critical for the development of XLP phenotypes.
      It appears therefore that the SAP/SH2D1A gene controls signaling via the SLAM
      family of surface receptors and thus may play a fundamental role in T cell and
      APC interactions during viral infections.

PMID- 11244051
TI  - Interleukin-10 and the interleukin-10 receptor.
AB  - Interleukin-10 (IL-10), first recognized for its ability to inhibit activation
      and effector function of T cells, monocytes, and macrophages, is a
      multifunctional cytokine with diverse effects on most hemopoietic cell types. The
      principal routine function of IL-10 appears to be to limit and ultimately
      terminate inflammatory responses. In addition to these activities, IL-10
      regulates growth and/or differentiation of B cells, NK cells, cytotoxic and
      helper T cells, mast cells, granulocytes, dendritic cells, keratinocytes, and
      endothelial cells. IL-10 plays a key role in differentiation and function of a
      newly appreciated type of T cell, the T regulatory cell, which may figure
      prominently in control of immune responses and tolerance in vivo. Uniquely among
      hemopoietic cytokines, IL-10 has closely related homologs in several virus
      genomes, which testify to its crucial role in regulating immune and inflammatory
      responses. This review highlights findings that have advanced our understanding
      of IL-10 and its receptor, as well as its in vivo function in health and disease.

PMID- 11244052
TI  - Genomic sequence and transcriptional analysis of a 23-kilobase mycobacterial
      linear plasmid: evidence for horizontal transfer and identification of plasmid
      maintenance systems.
AB  - Linear plasmids were unknown in mycobacteria until recently. Here, we report the
      complete nucleotide sequence of 23-kb linear plasmid pCLP from Mycobacterium
      celatum, an opportunistic pathogen. The sequence of pCLP revealed at least 19
      putative open reading frames (ORFs). Expression of pCLP genes in exponential
      phase cultures was determined by reverse transcriptase PCR (RT-PCR). Twelve ORFs
      were expressed, whereas no transcription of the 7 other ORFs of pCLP was
      detected. Five of the 12 transcribed ORFs detected by RT-PCR are of unknown
      function. Sequence analysis revealed similar loci in both M. celatum pCLP and the
      Mycobacterium tuberculosis chromosome, including transposase-related sequences.
      This result suggests horizontal transfer between these two organisms. pCLP also
      contains ORFs that are similar to genes of bacterial circular plasmids involved
      in partition (par operon) and postsegregational (pem operon) mechanisms.
      Functional analysis of these ORFs suggests that they probably carry out similar
      maintenance roles in pCLP.

PMID- 11244053
TI  - Viability of rep recA mutants depends on their capacity to cope with spontaneous
      oxidative damage and on the DnaK chaperone protein.
AB  - Replication arrests due to the lack or the inhibition of replicative helicases
      are processed by recombination proteins. Consequently, cells deficient in the Rep
      helicase, in which replication pauses are frequent, require the RecBCD
      recombination complex for growth. rep recA mutants are viable and display no
      growth defect at 37 or 42 degrees C. The putative role of chaperone proteins in
      rep and rep recA mutants was investigated by testing the effects of dnaK
      mutations. dnaK756 and dnaK306 mutations, which allow growth of otherwise wild
      type Escherichia coli cells at 40 degrees C, are lethal in rep recA mutants at
      this temperature. Furthermore, they affect the growth of rep mutants, and to a
      lesser extent, that of recA mutants. We conclude that both rep and recA mutants
      require DnaK for optimal growth, leading to low viability of the triple (rep recA
      dnaK) mutant. rep recA mutant cells form colonies at low efficiency when grown to
      exponential phase at 30 degrees C. Although the plating defect is not observed at
      a high temperature, it is not suppressed by overexpression of heat shock proteins
      at 30 degrees C. The plating defect of rep recA mutant cells is suppressed by the
      presence of catalase in the plates. The cryosensitivity of rep recA mutants
      therefore results from an increased sensitivity to oxidative damage upon
      propagation at low temperatures.

PMID- 11244054
TI  - Evidence that a linear megaplasmid encodes enzymes of aliphatic alkene and
      epoxide metabolism and coenzyme M (2-mercaptoethanesulfonate) biosynthesis in
      Xanthobacter strain Py2.
AB  - The bacterial metabolism of propylene proceeds by epoxidation to epoxypropane
      followed by a sequence of three reactions resulting in epoxide ring opening and
      carboxylation to form acetoacetate. Coenzyme M (2-mercaptoethanesulfonic acid)
      (CoM) plays a central role in epoxide carboxylation by serving as the nucleophile
      for epoxide ring opening and the carrier of the C(3) unit that is ultimately
      carboxylated to acetoacetate, releasing CoM. In the present work, a 320-kb linear
      megaplasmid has been identified in the gram-negative bacterium Xanthobacter
      strain Py2, which contains the genes encoding the key enzymes of propylene
      oxidation and epoxide carboxylation. Repeated subculturing of Xanthobacter strain
      Py2 under nonselective conditions, i.e., with glucose or acetate as the carbon
      source in the absence of propylene, resulted in the loss of the propylene
      positive phenotype. The propylene-negative phenotype correlated with the loss of
      the 320-kb linear megaplasmid, loss of induction and expression of alkene
      monooxgenase and epoxide carboxylation enzyme activities, and the loss of CoM
      biosynthetic capability. Sequence analysis of a hypothetical protein (XecG),
      encoded by a gene located downstream of the genes for the four enzymes of epoxide
      carboxylation, revealed a high degree of sequence identity with proteins of as
      yet unassigned functions in the methanogenic archaea Methanobacterium
      thermoautotrophicum and Methanococcus jannaschii and in Bacillus subtilis. The M.
      jannaschii homolog of XecG, MJ0255, is located next to a gene, MJ0256, that has
      been shown to encode a key enzyme of CoM biosynthesis (M. Graupner, H. Xu, and R.
      H. White, J. Bacteriol. 182: 4862-4867, 2000). We propose that the propylene
      positive phenotype of Xanthobacter strain Py2 is dependent on the selective
      maintenance of a linear megaplasmid containing the genes for the key enzymes of
      alkene oxidation, epoxide carboxylation, and CoM biosynthesis.

PMID- 11244055
TI  - Global analysis of Escherichia coli gene expression during the acetate-induced
      acid tolerance response.
AB  - The ability of Escherichia coli to survive at low pH is strongly affected by
      environmental factors, such as composition of the growth medium and growth phase.
      Exposure to short-chain fatty acids, such as acetate, proprionate, and butyrate,
      at neutral or nearly neutral pH has also been shown to increase acid survival of
      E. coli and Salmonella enterica serovar Typhimurium. To investigate the basis for
      acetate-induced acid tolerance in E. coli O157:H7, genes whose expression was
      altered by exposure to acetate were identified using gene arrays. The expression
      of 60 genes was reduced by at least twofold; of these, 48 encode components of
      the transcription-translation machinery. Expression of 26 genes increased twofold
      or greater following treatment with acetate. This included six genes whose
      products are known to be important for survival at low pH. Five of these genes,
      as well as six other acetate-induced genes, are members of the E. coli RpoS
      regulon. RpoS, the stress sigma factor, is known to be required for acid
      tolerance induced by growth at nonlethal low pH or by entry into stationary
      phase. Disruption of the rpoS gene by a transposon insertion mutation also
      prevented acetate-induced acid tolerance. However, induction of RpoS expression
      did not appear to be sufficient to activate the acid tolerance response.
      Treatment with either NaCl or sodium acetate (pH 7.0) increased expression of an
      rpoS::lacZ fusion protein, but only treatment with acetate increased acid
      survival.

PMID- 11244056
TI  - Physiological basis for conservation of the signal recognition particle targeting
      pathway in Escherichia coli.
AB  - The Escherichia coli signal recognition particle (SRP) is a ribonucleoprotein
      complex that targets nascent inner membrane proteins (IMPs) to transport sites in
      the inner membrane (IM). Since SRP depletion only partially inhibits IMP
      insertion under some growth conditions, however, it is not clear why the particle
      is absolutely essential for viability. Insights into this question emerged from
      experiments in which we analyzed the physiological consequences of reducing the
      intracellular concentration of SRP below the wild-type level. We found that even
      moderate SRP deficiencies that have little effect on cell growth led to the
      induction of a heat shock response. Genetic manipulations that suppress the heat
      shock response were lethal in SRP-deficient cells, indicating that the elevated
      synthesis of heat shock proteins plays an important role in maintaining cell
      viability. Although it is conceivable that the heat shock response serves to
      increase the capacity of cells to target IMPs via chaperone-based mechanisms, SRP
      deficient cells did not show an increased dependence on either GroEL or DnaK. By
      contrast, the heat shock-regulated proteases Lon and ClpQ became essential for
      viability when SRP levels were reduced. These results suggest that the heat shock
      response protects SRP-deficient cells by increasing their capacity to degrade
      mislocalized IMPs. Consistent with this notion, a model IMP that was mislocalized
      in the cytoplasm as the result of SRP depletion appeared to be more stable in a
      Deltalon DeltaclpQ strain than in control cells. Taken together, the data provide
      direct evidence that SRP is essential in E. coli and possibly conserved
      throughout prokaryotic evolution as well partly because efficient IMP targeting
      prevents a toxic accumulation of aggregated proteins in the cytoplasm.

PMID- 11244057
TI  - Modulation of actinorhodin biosynthesis in Streptomyces lividans by glucose
      repression of afsR2 gene transcription.
AB  - While the biosynthetic gene cluster encoding the pigmented antibiotic
      actinorhodin (ACT) is present in the two closely related bacterial species,
      Streptomyces lividans and Streptomyces coelicolor, it normally is expressed only
      in S. coelicolor-generating the deep-blue colonies responsible for the S.
      coelicolor name. However, multiple copies of the two regulatory genes, afsR and
      afsR2, activate ACT production in S. lividans, indicating that this streptomycete
      encodes a functional ACT biosynthetic pathway. Here we report that the occurrence
      of ACT biosynthesis in S. lividans is determined conditionally by the carbon
      source used for culture. We found that the growth of S. lividans on solid media
      containing glucose prevents ACT production in this species by repressing the
      synthesis of afsR2 mRNA; a shift to glycerol as the sole carbon source
      dramatically relieved this repression, leading to extensive ACT synthesis and
      obliterating this phenotypic distinction between S. lividans and S. coelicolor.
      Transcription from the afsR2 promoter during growth in glycerol was dependent on
      afsR gene function and was developmentally regulated, occurring specifically at
      the time of aerial mycelium formation and coinciding temporally with the onset of
      ACT production. In liquid media, where morphological differentiation does not
      occur, ACT production in the absence of glucose increased as S. lividans cells
      entered stationary phase, but unlike ACT biosynthesis on solid media, occurred by
      a mechanism that did not require either afsR or afsR2. Our results identify
      parallel medium-dependent pathways that regulate ACT biosynthesis in S. lividans
      and further demonstrate that the production of this antibiotic in S. lividans
      grown on agar can be modulated by carbon source through the regulation of afsR2
      mRNA synthesis.

PMID- 11244058
TI  - Genetic evidence that the alpha5 helix of the receiver domain of PhoB is involved
      in interdomain interactions.
AB  - Two-component signaling proteins are involved in transducing environmental
      stimuli into intracellular signals. Information is transmitted through a
      phosphorylation cascade that consists of a histidine protein kinase and a
      response regulator protein. Generally, response regulators are made up of a
      receiver domain and an output domain. Phosphorylation of the receiver domain
      modulates the activity of the output domain. The mechanisms by which receiver
      domains control the activities of their respective output domains are unknown. To
      address this question for the PhoB protein from Escherichia coli, we have
      employed two separate genetic approaches, deletion analysis and domain swapping.
      In-frame deletions were generated within the phoB gene, and the phenotypes of the
      mutants were analyzed. The output domain, by itself, retained significant ability
      to activate transcription of the phoA gene. However, another deletion mutant that
      contained the C-terminal alpha-helix of the receiver domain (alpha5) in addition
      to the entire output domain was unable to activate transcription of phoA. This
      result suggests that the alpha5 helix of the receiver domain interacts with and
      inhibits the output domain. We also constructed two chimeric proteins that join
      various parts of the chemotaxis response regulator, CheY, to PhoB. A chimera that
      joins the N-terminal approximately 85% of CheY's receiver domain to the beta5
      alpha5 loop of PhoB's receiver domain displayed phosphorylation-dependent
      activity. The results from both sets of experiments suggest that the regulation
      of PhoB involves the phosphorylation-mediated modulation of inhibitory contacts
      between the alpha5 helix of its unphosphorylated receiver domain and its output
      domain.

PMID- 11244059
TI  - Regulation of ornibactin biosynthesis and N-acyl-L-homoserine lactone production
      by CepR in Burkholderia cepacia.
AB  - The CepR-CepI quorum-sensing system has been shown to regulate production of the
      siderophore ornibactin, extracellular proteases, and N-octanoyl-homoserine-L
      lactone (OHL) in Burkholderia cepacia strain K56-2. To examine the effect of
      cepIR on production of other siderophores, cepR mutants were constructed in
      strains that produce pyochelin in addition to salicylic acid and ornibactins.
      Pc715j-R1 (cepR::tp) hyperproduced ornibactin but produced parental levels of
      pyochelin and salicylic acid, suggesting that CepR is a negative regulator of
      ornibactin synthesis but not pyochelin or salicylic acid. Pc715j-R1 was also
      protease deficient and OHL negative. The effects of cepR on ornibactin
      biosynthetic genes were examined by constructing cepR pvdA-lacZ and cepR pvdD
      lacZ mutants and monitoring beta-galactosidase activity. There was an increase in
      expression of pvdA in the cepR mutant compared to the level in its parent strain
      in both low- and high-iron media during stationary phase. When the outer membrane
      protein profiles of a cepR mutant and the wild-type strain were compared on
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis, there did not appear
      to be any difference in levels of expression of the ornibactin receptor.
      Experiments with cepI-lacZ and cepR-lacZ transcriptional fusions indicated that
      cepI was not expressed in the cepR mutant and that cepR acts as a negative
      regulator of its own expression. By a thin-layer chromatography assay for N-acyl
      homoserine lactones, OHL and N-hexanoyl-L-homoserine lactone (HHL) were
      detectable in K56-2 and Pc715j, both wild-type strains. OHL was not detectable
      and HHL was only weakly detectable in the cepI and cepR mutants. These results
      suggest that CepR is both a positive and negative transcriptional regulator and
      that CepR may influence the expression of ornibactin biosynthetic genes in
      addition to the expression of the cepIR quorum-sensing system.

PMID- 11244060
TI  - Determination of Wolbachia genome size by pulsed-field gel electrophoresis.
AB  - Genome sizes of six different Wolbachia strains from insect and nematode hosts
      have been determined by pulsed-field gel electrophoresis of purified DNA both
      before and after digestion with rare-cutting restriction endonucleases. Enzymes
      SmaI, ApaI, AscI, and FseI cleaved the studied Wolbachia strains at a small
      number of sites and were used for the determination of the genome sizes of
      wMelPop, wMel, and wMelCS (each 1.36 Mb), wRi (1.66 Mb), wBma (1.1 Mb), and wDim
      (0.95 Mb). The Wolbachia genomes studied were all much smaller than the genomes
      of free-living bacteria such as Escherichia coli (4.7 Mb), as is typical for
      obligate intracellular bacteria. There was considerable genome size variability
      among Wolbachia strains, especially between the more parasitic A group Wolbachia
      infections of insects and the mutualistic C and D group infections of nematodes.
      The studies described here found no evidence for extrachromosomal plasmid DNA in
      any of the strains examined. They also indicated that the Wolbachia genome is
      circular.

PMID- 11244061
TI  - Functional characterization of alanine racemase from Schizosaccharomyces pombe: a
      eucaryotic counterpart to bacterial alanine racemase.
AB  - Schizosaccharomyces pombe has an open reading frame, which we named alr1(+),
      encoding a putative protein similar to bacterial alanine racemase. We cloned the
      alr1(+) gene in Escherichia coli and purified the gene product (Alr1p), with an
      M(r) of 41,590, to homogeneity. Alr1p contains pyridoxal 5'-phosphate as a
      coenzyme and catalyzes the racemization of alanine with apparent K(m) and V(max)
      values as follows: for L-alanine, 5.0 mM and 670 micromol/min/mg, respectively,
      and for D-alanine, 2.4 mM and 350 micromol/min/mg, respectively. The enzyme is
      almost specific to alanine, but L-serine and L-2-aminobutyrate are racemized
      slowly at rates 3.7 and 0.37% of that of L-alanine, respectively. S. pombe uses D
      alanine as a sole nitrogen source, but deletion of the alr1(+) gene resulted in
      retarded growth on the same medium. This indicates that S. pombe has catabolic
      pathways for both enantiomers of alanine and that the pathway for L-alanine
      coupled with racemization plays a major role in the catabolism of D-alanine.
      Saccharomyces cerevisiae differs markedly from S. pombe: S. cerevisiae uses L
      alanine but not D-alanine as a sole nitrogen source. Moreover, D-alanine is toxic
      to S. cerevisiae. However, heterologous expression of the alr1(+) gene enabled S.
      cerevisiae to grow efficiently on D-alanine as a sole nitrogen source. The
      recombinant yeast was relieved from the toxicity of D-alanine.

PMID- 11244062
TI  - Altered pathway routing in a class of Salmonella enterica serovar Typhimurium
      mutants defective in aminoimidazole ribonucleotide synthetase.
AB  - In Salmonella enterica serovar Typhimurium, purine nucleotides and thiamine are
      synthesized by a branched pathway. The last known common intermediate,
      aminoimidazole ribonucleotide (AIR), is formed from formylglycinamidine
      ribonucleotide (FGAM) and ATP by AIR synthetase, encoded by the purI gene in S.
      enterica. Reduced flux through the first five steps of de novo purine synthesis
      results in a requirement for purines but not necessarily thiamine. To examine the
      relationship between the purine and thiamine biosynthetic pathways, purI mutants
      were made (J. L. Zilles and D. M. Downs, Genetics 143:37-44, 1996). Unexpectedly,
      some mutant purI alleles (R35C/E57G and K31N/A50G/L218R) allowed growth on
      minimal medium but resulted in thiamine auxotrophy when exogenous purines were
      supplied. To explain the biochemical basis for this phenotype, the R35C/E57G
      mutant PurI protein was purified and characterized kinetically. The K(m) of the
      mutant enzyme for FGAM was unchanged relative to the wild-type enzyme, but the
      V(max) was decreased 2.5-fold. The K(m) for ATP of the mutant enzyme was 13-fold
      increased. Genetic analysis determined that reduced flux through the purine
      pathway prevented PurI activity in the mutant strain, and purR null mutations
      suppressed this defect. The data are consistent with the hypothesis that an
      increased FGAM concentration has the ability to compensate for the lower affinity
      of the mutant PurI protein for ATP.

PMID- 11244063
TI  - Evolutionary divergence of an elongation factor 3 from Cryptococcus neoformans.
AB  - Elongation factor 3 (EF3) is considered a promising drug target for the control
      of fungal diseases because of its requirement for protein synthesis and survival
      of fungi and a lack of EF3 in the mammalian host. However, EF3 has been
      characterized only in ascomycete yeast. In order to understand the role of EF3 in
      a basidiomycete yeast, we cloned the gene encoding EF3 from Cryptococcus
      neoformans (CnEF3), an important fungal pathogen in immunocompromised patients,
      including those infected with human immunodeficiency virus. CnEF3 was found to
      encode a 1,055-amino-acid protein and has 44% identity with EF3 from
      Saccharomyces cerevisiae (YEF3). Expressed CnEF3 exhibited ATPase activity that
      was only modestly stimulated by ribosomes from S. cerevisiae. In contrast, CnEF3
      showed tight binding to cryptococcal ribosomes, as shown by an inability to be
      removed under conditions which successfully remove Saccharomyces EF3 from
      ribosomes (0.5 M KCl or 2 M LiCl). CnEF3 also poorly complemented a YEF3 defect
      in a diploid null mutant and two temperature-sensitive mutants which have been
      shown previously to be complemented well by EF3 from other ascomycetes, such as
      Candida albicans. These data clearly identify the presence of a functioning EF3
      in the basidiomycete yeast C. neoformans, which demonstrates an evolutionary
      divergence from EF3 of ascomycete yeast.

PMID- 11244064
TI  - SirA orthologs affect both motility and virulence.
AB  - The sirA gene of Salmonella enterica serovar Typhimurium encodes a two-component
      response regulator of the FixJ family that has a positive regulatory influence on
      the expression of type III secretion genes involved with epithelial cell invasion
      and the elicitation of bovine gastroenteritis. SirA orthologs in Pseudomonas,
      Vibrio, and Erwinia control the expression of distinct virulence genes in these
      genera, but an evolutionarily conserved target of SirA regulation has never been
      identified. In this study we tested the hypothesis that sirA may be an ancient
      member of the flagellar regulon. We examined the effect of a sirA mutation on
      transcriptional fusions to flagellar promoters (flhD, fliE, fliF, flgA, flgB,
      fliC, fliD, motA, and fliA) while using fusions to the virulence gene sopB as a
      positive control. SirA had only small regulatory effects on all fusions in liquid
      medium (less than fivefold). However, in various types of motility agar plates,
      sirA was able to activate a sopB fusion by up to 63-fold while repressing
      flagellar fusions by values exceeding 100-fold. Mutations in the sirA orthologs
      of Escherichia coli, Vibrio cholerae, Pseudomonas fluorescens, and Pseudomonas
      aeruginosa result in defects in either motility or motility gene regulation,
      suggesting that control of flagellar regulons may be an evolutionarily conserved
      function of sirA orthologs. The implications for our understanding of virulence
      gene regulation in the gamma Proteobacteria are discussed.

PMID- 11244065
TI  - In vivo titration of mitomycin C action by four Escherichia coli genomic regions
      on multicopy plasmids.
AB  - Mitomycin C (MMC), a DNA-damaging agent, is a potent inducer of the bacterial SOS
      response; surprisingly, it has not been used to select resistant mutants from
      wild-type Escherichia coli. MMC resistance is caused by the presence of any of
      four distinct E. coli genes (mdfA, gyrl, rob, and sdiA) on high-copy-number
      vectors. mdfA encodes a membrane efflux pump whose overexpression results in
      broad-spectrum chemical resistance. The gyrI (also called sbmC) gene product
      inhibits DNA gyrase activity in vitro, while the rob protein appears to function
      in transcriptional activation of efflux pumps. SdiA is a transcriptional
      activator of ftsQAZ genes involved in cell division.

PMID- 11244066
TI  - Global impact of sdiA amplification revealed by comprehensive gene expression
      profiling of Escherichia coli.
AB  - In Escherichia coli the amplification of sdiA, a positive activator of ftsQAZ,
      genes that are essential for septation, results in mitomycin C resistance. To
      help us understand this resistance phenotype, genes whose expression was altered
      by increased sdiA dosage were identified using a DNA microarray-based,
      comprehensive transcript profiling method. The expression of 62 genes was reduced
      by more than threefold; of these, 41 are involved in motility and chemotaxis.
      Moreover, the expression of 75 genes, 36 of which had been previously
      characterized, was elevated at least threefold. As expected, increased sdiA
      dosage led to significantly elevated sdiA and 'ddlB-ftsQAZ-lpxC operon
      expression. Transcription of two genes, uvrY and uvrC, located downstream of sdiA
      and oriented in the same direction, was elevated about 10-fold, although the
      intervening gene, yecF, of opposite polarity was unaffected by increased sdiA
      dosage. Three genes (mioC and gidAB) flanking the replication origin, oriC, were
      transcribed more often when sdiA dosage was high, as were 12 genes within 1 min
      of a terminus of replication, terB. Transcription of the acrABDEF genes, mapping
      in three widely spaced loci, was elevated significantly, while several genes
      involved in DNA repair and replication (e.g., nei, recN, mioC, and mcrC) were
      moderately elevated in expression. Such global analysis provides a link between
      septation and the response to DNA-damaging agents.

PMID- 11244067
TI  - Glucan synthase complex of Aspergillus fumigatus.
AB  - The glucan synthase complex of the human pathogenic mold Aspergillus fumigatus
      has been investigated. The genes encoding the putative catalytic subunit Fks1p
      and four Rho proteins of A. fumigatus were cloned and sequenced. Sequence
      analysis showed that AfFks1p was a transmembrane protein very similar to other
      Fksp proteins in yeasts and in Aspergillus nidulans. Heterologous expression of
      the conserved internal hydrophilic domain of AfFks1p was achieved in Escherichia
      coli. Anti-Fks1p antibodies labeled the apex of the germ tube, as did aniline
      blue fluorochrome, which was specific for beta(1-3) glucans, showing that AfFks1p
      colocalized with the newly synthesized beta(1-3) glucans. AfRHO1, the most
      homologous gene to RHO1 of Saccharomyces cerevisiae, was studied for the first
      time in a filamentous fungus. AfRho proteins have GTP binding and hydrolysis
      consensus sequences identical to those of yeast Rho proteins and have a slightly
      modified geranylation site in AfRho1p and AfRho3p. Purification of the glucan
      synthase complex by product entrapment led to the enrichment of four proteins:
      Fks1p, Rho1p, a 100-kDa protein homologous to a membrane H(+)-ATPase, and a 160
      kDa protein which was labeled by an anti-beta(1-3) glucan antibody and was
      homologous to ABC bacterial beta(1-2) glucan transporters.

PMID- 11244068
TI  - Structure, expression, and functional analysis of the gene coding for calmodulin
      in the chytridiomycete Blastocladiella emersonii.
AB  - The single calmodulin (CaM) gene and the corresponding cDNA of the
      chytridiomycete Blastocladiella emersonii were isolated and characterized. The
      CaM gene is interrupted by three introns and transcribed in a single 0.7-kb mRNA
      species encoding a predicted protein 91% identical to human CaM. B. emersonii CaM
      has been expressed in Escherichia coli as a fusion protein with gluthatione S
      transferase (GST) and purified by affinity chromatography and cleavage from the
      GST portion using a site-specific protease. In the presence of Ca(2+), B.
      emersonii CaM exhibited a shift in apparent molecular mass similar to that
      observed with bovine CaM and was able to activate the autophosphorylation of CaM
      dependent protein kinase II (CaMKII) from rat brain. CaM expression is
      developmentally regulated in B. emersonii, with CaM mRNA and protein
      concentrations increasing during sporulation to maximum levels observed just
      prior to the release of the zoospores into the medium. Both CaM protein and mRNA
      levels decrease drastically at the zoospore stage, increasing again during
      germination. The CaM antagonists compound 48/80, calmidazolium, and W7 were shown
      to completely inhibit B. emersonii sporulation when added to the cultures at
      least 120, 150, and 180 min after induction, respectively. All these drugs also
      inhibited growth and zoospore production in this fungus. The Ca(2+) channel
      blocker TMB-8 and the CaMKII inhibitor KN93 completely inhibited sporulation if
      added up to 60 min after induction of this stage, but only KN93 affected fungal
      growth. The data presented suggest that the Ca(2+)-CaM complex and CaMKII play an
      important role during growth and sporulation in B. emersonii.

PMID- 11244070
TI  - Gene transfer to the desiccation-tolerant cyanobacterium Chroococcidiopsis.
AB  - The coccoid cyanobacterium Chroococcidiopsis dominates microbial communities in
      the most extreme arid hot and cold deserts. These communities withstand
      constraints that result from multiple cycles of drying and wetting and/or
      prolonged desiccation, through mechanisms which remain poorly understood. Here we
      describe the first system for genetic manipulation of Chroococcidiopsis. Plasmids
      pDUCA7 and pRL489, based on the pDU1 replicon of Nostoc sp. strain PCC 7524, were
      transferred to different isolates of Chroococcidiopsis via conjugation and
      electroporation. This report provides the first evidence that pDU1 replicons can
      be maintained in cyanobacteria other than Nostoc and Anabaena. Following
      conjugation, both plasmids replicated in Chroococcidiopsis sp. strains 029, 057,
      and 123 but not in strains 171 and 584. Both plasmids were electroporated into
      strains 029 and 123 but not into strains 057, 171, and 584. Expression of P(psbA)
      luxAB on pRL489 was visualized through in vivo luminescence. Efficiencies of
      conjugative transfer for pDUCA7 and pRL489 into Chroococcidiopsis sp. strain 029
      were approximately 10(-2) and 10(-4) transconjugants per recipient cell,
      respectively. Conjugative transfer occurred with a lower efficiency into strains
      057 and 123. Electrotransformation efficiencies of about 10(-4)
      electrotransformants per recipient cell were achieved with strains 029 and 123,
      using either pDUCA7 or pRL489. Extracellular deoxyribonucleases were associated
      with each of the five strains. Phylogenetic analysis, based upon the V6 to V8
      variable regions of 16S rRNA, suggests that desert strains 057, 123, 171, and 029
      are distinct from the type species strain Chroococcidiopsis thermalis PCC 7203.
      The high efficiency of conjugative transfer of Chroococcidiopsis sp. strain 029,
      from the Negev Desert, Israel, makes this a suitable experimental strain for
      genetic studies on desiccation tolerance.

PMID- 11244069
TI  - Substitutions in bacteriophage T4 AsiA and Escherichia coli sigma(70) that
      suppress T4 motA activation mutations.
AB  - Bacteriophage T4 middle-mode transcription requires two phage-encoded proteins,
      the MotA transcription factor and AsiA coactivator, along with Escherichia coli
      RNA polymerase holoenzyme containing the sigma(70) subunit. A motA positive
      control (pc) mutant, motA-pc1, was used to select for suppressor mutations that
      alter other proteins in the transcription complex. Separate genetic selections
      isolated two AsiA mutants (S22F and Q51E) and five sigma(70) mutants (Y571C,
      Y571H, D570N, L595P, and S604P). All seven suppressor mutants gave partial
      suppressor phenotypes in vivo as judged by plaque morphology and burst size
      measurements. The S22F mutant AsiA protein and glutathione S-transferase fusions
      of the five mutant sigma(70) proteins were purified. All of these mutant proteins
      allowed normal levels of in vitro transcription when tested with wild-type MotA
      protein, but they failed to suppress the mutant MotA-pc1 protein in the same
      assay. The sigma(70) substitutions affected the 4.2 region, which binds the -35
      sequence of E. coli promoters. In the presence of E. coli RNA polymerase without
      T4 proteins, the L595P and S604P substitutions greatly decreased transcription
      from standard E. coli promoters. This defect could not be explained solely by a
      disruption in -35 recognition since similar results were obtained with extended 
      10 promoters. The generalized transcriptional defect of these two mutants
      correlated with a defect in binding to core RNA polymerase, as judged by
      immunoprecipitation analysis. The L595P mutant, which was the most defective for
      in vitro transcription, failed to support E. coli growth.

PMID- 11244071
TI  - Functional domains of yeast plasmid-encoded Rep proteins.
AB  - Both of the Saccharomyces cerevisiae 2 microm circle-encoded Rep1 and Rep2
      proteins are required for efficient distribution of the plasmid to daughter cells
      during cellular division. In this study two-hybrid and in vitro protein
      interaction assays demonstrate that the first 129 amino acids of Rep1 are
      sufficient for self-association and for interaction with Rep2. Deletion of the
      first 76 amino acids of Rep1 abolished the Rep1-Rep2 interaction but still
      allowed some self-association, suggesting that different but overlapping domains
      specify these interactions. Amino- or carboxy-terminally truncated Rep1 fusion
      proteins were unable to complement defective segregation of a 2 microm-based
      stability vector with rep1 deleted, supporting the idea of the requirement of Rep
      protein interaction for plasmid segregation but indicating a separate required
      function for the carboxy-terminal portion of Rep1. The results of in vitro
      baiting assays suggest that Rep2 contains two nonoverlapping domains, both of
      which are capable of mediating Rep2 self-association. The amino-terminal domain
      interacts with Rep1, while the carboxy-terminal domain was shown by Southwestern
      analysis to have DNA-binding activity. The overlapping Rep1 and Rep2 interaction
      domains in Rep1, and the ability of Rep2 to interact with Rep1, Rep2, and DNA,
      suggest a model in which the Rep proteins polymerize along the 2 microm circle
      plasmid stability locus, forming a structure that mediates plasmid segregation.
      In this model, competition between Rep1 and Rep2 for association with Rep1
      determines the formation or disassembly of the segregation complex.

PMID- 11244072
TI  - Loss of ribosomal protein L11 blocks stress activation of the Bacillus subtilis
      transcription factor sigma(B).
AB  - sigma(B), the general stress response sigma factor of Bacillus subtilis, is
      activated when the cell's energy levels decline or the bacterium is exposed to
      environmental stress (e.g., heat shock, ethanol). Physical stress activates
      sigma(B) through a collection of regulatory kinases and phosphatases (the Rsb
      proteins) which catalyze the release of sigma(B) from an anti-sigma(B) factor
      inhibitor. The means by which diverse stresses communicate with the Rsb proteins
      is unknown; however, a role for the ribosome in this process was suggested when
      several of the upstream members of the sigma(B) stress activation cascade (RsbR, 
      S, and -T) were found to cofractionate with ribosomes in crude B. subtilis
      extracts. We now present evidence for the involvement of a ribosome-mediated
      process in the stress activation of sigma(B). B. subtilis strains resistant to
      the antibiotic thiostrepton, due to the loss of ribosomal protein L11 (RplK),
      were found to be blocked in the stress activation of sigma(B). Neither the energy
      responsive activation of sigma(B) nor stress-dependent chaperone gene induction
      (a sigma(B)-independent stress response) was inhibited by the loss of L11. The
      Rsb proteins required for stress activation of sigma(B) are shown to be active in
      the RplK(-) strain but fail to be triggered by stress. The data demonstrate that
      the B. subtilis ribosomes provide an essential input for the stress activation of
      sigma(B) and suggest that the ribosomes may themselves be the sensors for stress
      in this system.

PMID- 11244073
TI  - Altering catalytic properties of 3-chlorocatechol-oxidizing extradiol dioxygenase
      from Sphingomonas xenophaga BN6 by random mutagenesis.
AB  - The 2,3-dihydroxybiphenyl 1,2-dioxygenase from Sphingomonas xenophaga strain BN6
      (BphC1) oxidizes 3-chlorocatechol by a rather unique distal ring cleavage
      mechanism. In an effort to improve the efficiency of this reaction, bphC1 was
      randomly mutated by error-prone PCR. Mutants which showed increased activities
      for 3-chlorocatechol were obtained, and the mutant forms of the enzyme were shown
      to contain two or three amino acid substitutions. Variant enzymes containing
      single substitutions were constructed, and the amino acid substitutions
      responsible for altered enzyme properties were identified. One variant enzyme,
      which contained an exchanged amino acid in the C-terminal part, revealed a higher
      level of stability during conversion of 3-chlorocatechol than the wild-type
      enzyme. Two other variant enzymes contained amino acid substitutions in a region
      of the enzyme that is considered to be involved in substrate binding. These two
      variant enzymes exhibited a significantly altered substrate specificity and an
      about fivefold-higher reaction rate for 3-chlorocatechol conversion than the wild
      type enzyme. Furthermore, these variant enzymes showed the novel capability to
      oxidize 3-methylcatechol and 2,3-dihydroxybiphenyl by a distal cleavage
      mechanism.

PMID- 11244074
TI  - TOR modulates GCN4-dependent expression of genes turned on by nitrogen
      limitation.
AB  - In Saccharomyces cerevisiae, the rapamycin-sensitive TOR signaling pathway plays
      an essential role in up-regulating translation initiation and cell cycle
      progression in response to nutrient availability. One of the mechanisms by which
      TOR regulates cell proliferation is by excluding the GLN3 transcriptional
      activator from the nucleus and, in consequence, preventing its transcriptional
      activation therein. We examined the possibility that the TOR cascade could also
      control the transcriptional activity of Gcn4p, which is known to respond to amino
      acid availability. The results presented in this paper indicate that GCN4 plays a
      role in the rapamycin-sensitive signaling pathway, regulating the expression of
      genes involved in the utilization of poor nitrogen sources, a previously
      unrecognized role for Gcn4p, and that the TOR pathway controls GCN4 activity by
      regulating the translation of GCN4 mRNA. This constitutes an additional TOR
      dependent mechanism which modulates the action of transcriptional activators.

PMID- 11244075
TI  - Engineered fatty acid biosynthesis in Streptomyces by altered catalytic function
      of beta-ketoacyl-acyl carrier protein synthase III.
AB  - The Streptomyces glaucescens beta-ketoacyl-acyl carrier protein (ACP) synthase
      III (KASIII) initiates straight- and branched-chain fatty acid biosynthesis by
      catalyzing the decarboxylative condensation of malonyl-ACP with different acyl
      coenzyme A (CoA) primers. This KASIII has one cysteine residue, which is critical
      for forming an acyl-enzyme intermediate in the first step of the process. Three
      mutants (Cys122Ala, Cys122Ser, Cys122Gln) were created by site-directed
      mutagenesis. Plasmid-based expression of these mutants in S. glaucescens resulted
      in strains which generated 75 (Cys122Ala) to 500% (Cys122Gln) more straight-chain
      fatty acids (SCFA) than the corresponding wild-type strain. In contrast, plasmid
      based expression of wild-type KASIII had no effect on fatty acid profiles. These
      observations are attributed to an uncoupling of the condensation and
      decarboxylation activities in these mutants (malonyl-ACP is thus converted to
      acetyl-ACP, a SCFA precursor). Incorporation experiments with perdeuterated
      acetic acid demonstrated that 9% of the palmitate pool of the wild-type strain
      was generated from an intact D(3) acetyl-CoA starter unit, compared to 3% in a
      strain expressing the Cys122Gln KASIII. These observations support the
      intermediacy of malonyl-ACP in generating the SCFA precursor in a strain
      expressing this mutant. To study malonyl-ACP decarboxylase activity in vitro, the
      KASIII mutants were expressed and purified as His-tagged proteins in Escherichia
      coli and assayed. In the absence of the acyl-CoA substrate the Cys122Gln mutant
      and wild-type KASIII were shown to have comparable decarboxylase activities in
      vitro. The Cys122Ala mutant exhibited higher activity. This activity was
      inhibited for all enzymes by the presence of high concentrations of isobutyryl
      CoA (>100 microM), a branched-chain fatty acid biosynthetic precursor. Under
      these conditions the mutant enzymes had no activity, while the wild-type enzyme
      functioned as a ketoacyl synthase. These observations indicate the likely upper
      and lower limits of isobutyryl-CoA and related acyl-CoA concentrations within S.
      glaucescens.

PMID- 11244076
TI  - Heteromeric interactions among nucleoid-associated bacterial proteins:
      localization of StpA-stabilizing regions in H-NS of Escherichia coli.
AB  - The nucleoid-associated proteins H-NS and StpA in Escherichia coli bind DNA as
      oligomers and are implicated in gene regulatory systems. There is evidence for
      both homomeric and heteromeric H-NS-StpA complexes. The two proteins show
      differential turnover, and StpA was previously found to be subject to protease
      mediated degradation by the Lon protease. We investigated which regions of the H
      NS protein are able to prevent degradation of StpA. A set of truncated H-NS
      derivatives was tested for their ability to mediate StpA stability and to form
      heteromers in vitro. The data indicate that H-NS interacts with StpA at two
      regions and that the presence of at least one of the H-NS regions is necessary
      for StpA stability. Our results also suggest that a proteolytically stable form
      of StpA, StpA(F21C), forms dimers, whereas wild-type StpA in the absence of H-NS
      predominantly forms tetramers or oligomers, which are more susceptible to
      proteolysis.

PMID- 11244077
TI  - Salmonella host cell invasion emerged by acquisition of a mosaic of separate
      genetic elements, including Salmonella pathogenicity island 1 (SPI1), SPI5, and
      sopE2.
AB  - Salmonella spp. possess a conserved type III secretion system encoded within the
      pathogenicity island 1 (SPI1; centisome 63), which mediates translocation of
      effector proteins into the host cell cytosol to trigger responses such as
      bacterial internalization. Several translocated effector proteins are encoded in
      other regions of the Salmonella chromosome. It remains unclear how this complex
      chromosomal arrangement of genes for the type III apparatus and the effector
      proteins emerged and how the different effector proteins cooperate to mediate
      virulence. By Southern blotting, PCR, and phylogenetic analyses of highly diverse
      Salmonella spp., we show here that effector protein genes located in the core of
      SPI1 are present in all Salmonella lineages. Surprisingly, the same holds true
      for several effector protein genes located in distant regions of the Salmonella
      chromosome, namely, sopB (SPI5, centisome 20), sopD (centisome 64), and sopE2
      (centisomes 40 to 42). Our data demonstrate that sopB, sopD, and sopE2, along
      with SPI1, were already present in the last common ancestor of all contemporary
      Salmonella spp. Analysis of Salmonella mutants revealed that host cell invasion
      is mediated by SopB, SopE2, and, in the case of Salmonella enterica serovar
      Typhimurium SL1344, by SopE: a sopB sopE sopE2-deficient triple mutant was
      incapable of inducing membrane ruffling and was >100-fold attenuated in host cell
      invasion. We conclude that host cell invasion emerged early during evolution by
      acquisition of a mosaic of genetic elements (SPI1 itself, SPI5 [sopB], and sopE2)
      and that the last common ancestor of all contemporary Salmonella spp. was
      probably already invasive.

PMID- 11244079
TI  - A mutation in the 5' untranslated region increases stability of norA mRNA,
      encoding a multidrug resistance transporter of Staphylococcus aureus.
AB  - NorA, a multidrug efflux pump in Staphylococcus aureus, protects the cell from
      multiple drugs, including quinolones. The flqB mutation (T-->G) in the 5'
      untranslated region upstream of norA causes norA overexpression of 4.9-fold in
      cis, as measured in norA::blaZ fusions. The transcriptional initiation site of
      norA was unchanged in mutant and wild-type strains, but the half-life of norA
      mRNA was increased 4.8-fold in the flqB mutant compared to the wild-type strain.
      Computer-generated folding of the first 68 nucleotides of the norA transcript
      predicts an additional stem-loop and changes in a putative RNase III cleavage
      site in the flqB mutant.

PMID- 11244078
TI  - Pseudomonas stutzeri has two closely related pilA genes (Type IV pilus structural
      protein) with opposite influences on natural genetic transformation.
AB  - Pseudomonas stutzeri has type IV pili for which the pilA gene (here termed pilAI)
      provides the structural protein and which are required for DNA uptake and natural
      genetic transformation. Downstream of pilAI we identified a gene, termed pilAII,
      coding for a deduced protein with a size similar to that of PilAI with 55% amino
      acid sequence identity and with a typical leader peptide including a leader
      peptidase cleavage site. Fusions to lacZ revealed that pilAII is expressed only
      about 10% compared to pilAI, although the genes are cotranscribed as shown by
      reverse transcription-PCR. Surprisingly, insertional inactivation of pilAII
      produced a hypertransformation phenotype giving about 16-fold-increased
      transformation frequencies. Hypertransformation also occurred in pilAI pilAII
      double mutants expressing heterologous pilA genes of nontransformable bacteria,
      like Pseudomonas aeruginosa or Dichelobacter nodosus. The overexpression of
      pilAII decreased transformation up to 5,000-fold compared to that of the pilAII
      mutant. However, neither inactivation of pilAII nor its overexpression affected
      the amounts of [(3)H]thymidine-labeled DNA that were competence-specifically
      bound and taken up by the cells. In the pilAII mutant, the transformation by
      purified single-stranded DNA (which depends on comA and exbB, as does
      transformation by duplex DNA) was also increased 17-fold. It is concluded that
      PilAII suppresses a step in transformation after the uptake of duplex DNA into
      the cell and perhaps before its translocation into the cytoplasm. The idea that
      the degree of the transformability of cells could be permanently adjusted by the
      expression level of an antagonistic protein is discussed.

PMID- 11244080
TI  - Conservative duplication of spindle poles during meiosis in Saccharomyces
      cerevisiae.
AB  - During sporulation in diploid Saccharomyces cerevisiae, spindle pole bodies
      acquire the so-called meiotic plaque, a prerequisite for spore formation. Mpc70p
      is a component of the meiotic plaque and is thus essential for spore formation.
      We show here that MPC70/mpc70 heterozygous strains most often produce two spores
      instead of four and that these spores are always nonsisters. In wild-type
      strains, Mpc70p localizes to all four spindle pole bodies, whereas in MPC70/mpc70
      strains Mpc70p localizes to only two of the four spindle pole bodies, and these
      are always nonsisters. Our data can be explained by conservative spindle pole
      body distribution in which the two newly synthesized meiosis II spindle pole
      bodies of MPC70/mpc70 strains lack Mpc70p.

PMID- 11244081
TI  - Establishing lysogenic transcription in the temperate coliphage 186.
AB  - A single-copy chromosomal reporter system was used to measure the intrinsic
      strengths and interactions between the three promoters involved in the
      establishment of lysogeny by coliphage 186. The maintenance lysogenic promoter
      p(L) for the immunity repressor gene cI is intrinsically approximately 20-fold
      weaker than the lytic promoter p(R). These promoters are arranged face-to-face,
      and transcription from p(L) is further weakened some 14-fold by the activity of
      p(R). Efficient establishment of lysogeny requires the p(E) promoter, which lies
      upstream of p(L) and is activated by the phage CII protein to a level comparable
      to that of p(R). Transcription of p(E) is less sensitive to converging p(R)
      transcription and raises cI transcription at least 55-fold. The p(E) promoter
      does not occlude p(L) but inhibits lytic transcription by 50%. This interference
      is not due to bound CII preventing elongation of the lytic transcript. The p(E)
      RNA is antisense to the anti-immune repressor gene apl, but any role of this in
      the establishment of lysogeny appears to be minimal.

PMID- 11244083
TI  - In vitro transposition system for efficient generation of random mutants of
      Campylobacter jejuni.
AB  - Campylobacter jejuni is the most common cause of food-borne illnesses in the
      United States. Despite the fact that the entire nucleotide sequence of its genome
      has recently become available, its mechanisms of pathogenicity are poorly
      understood. This is in part due to the lack of an efficient mutagenesis system.
      Here we describe an in vitro transposon mutagenesis system based on the
      Staphylococcus aureus transposable element Tn552 that allows the efficient
      generation of insertion mutants of C. jejuni. Insertions occur randomly and
      throughout the entire bacterial genome. We have tested this system in the
      isolation of nonmotile mutants of C. jejuni. Demonstrating the utility of the
      system, six nonmotile mutants from a total of nine exhibited insertions in genes
      known to be associated with motility. An additional mutant had an inactivating
      insertion in sigma 54, implicating this transcription factor in flagellum
      regulation. The availability of this efficient system will greatly facilitate the
      study of the mechanisms of pathogenesis of this important pathogen.

PMID- 11244082
TI  - FosB, a cysteine-dependent fosfomycin resistance protein under the control of
      sigma(W), an extracytoplasmic-function sigma factor in Bacillus subtilis.
AB  - We demonstrate that the Bacillus subtilis fosB(yndN) gene encodes a fosfomycin
      resistance protein. Expression of fosB requires sigma(W), and both fosB and sigW
      mutants are fosfomycin sensitive. FosB is a metallothiol transferase related to
      the FosA class of Mn(2+)-dependent glutathione transferases but with a preference
      for Mg(2+) and L-cysteine as cofactors.

PMID- 11244084
TI  - Transcriptional activation of the Bacillus subtilis ackA promoter requires
      sequences upstream of the CcpA binding site.
AB  - Carbon catabolite protein A (CcpA) is a global regulator of carbon metabolism in
      gram-positive bacteria, repressing transcription of genes for the utilization of
      secondary carbon sources in the presence of a readily metabolized carbon source
      and activating transcription of genes, such as ackA and pta, that are required
      for carbon excretion. The promoter region of the Bacillus subtilis ackA gene
      contains two catabolite responsive elements (cre sites), of which only the site
      closest to the promoter (cre2) binds CcpA to activate transcription. A region
      immediately upstream of the cre2 site is also important for transcriptional
      activation. The required elements in this region were further defined by
      mutagenesis. CcpA binds to the ackA promoter region in gel shift assays even in
      the presence of mutations in the upstream element that block transcriptional
      activation, indicating that this region has a function other than promoting
      binding of CcpA.

PMID- 11244085
TI  - New insight into the role of the PhaP phasin of Ralstonia eutropha in promoting
      synthesis of polyhydroxybutyrate.
AB  - Phasins are proteins that are proposed to play important roles in
      polyhydroxyalkanoate synthesis and granule formation. Here the phasin PhaP of
      Ralstonia eutropha has been analyzed with regard to its role in the synthesis of
      polyhydroxybutyrate (PHB). Purified recombinant PhaP, antibodies against PhaP,
      and an R. eutropha phaP deletion strain have been generated for this analysis.
      Studies with the phaP deletion strain show that PhaP must accumulate to high
      levels in order to play its normal role in PHB synthesis and that the
      accumulation of PhaP to low levels is functionally equivalent to the absence of
      PhaP. PhaP positively affects PHB synthesis under growth conditions which promote
      production of PHB to low, intermediate, or high levels. The levels of PhaP
      generally parallel levels of PHB in cells. The results are consistent with models
      whereby PhaP promotes PHB synthesis by regulating the surface/volume ratio of PHB
      granules or by interacting with polyhydroxyalkanoate synthase and indicate that
      PhaP plays an important role in PHB synthesis from the early stages in PHB
      production and across a range of growth conditions.

PMID- 11244086
TI  - Regulation of the cystic fibrosis transmembrane conductance regulator Cl- channel
      by its R domain.

PMID- 11244087
TI  - A novel family of phosphatidylinositol 4-kinases conserved from yeast to humans.
AB  - Phosphatidylinositolpolyphosphates (PIPs) are centrally involved in many
      biological processes, ranging from cell growth and organization of the actin
      cytoskeleton to endo- and exocytosis. Phosphorylation of phosphatidylinositol at
      the D-4 position, an essential step in the biosynthesis of PIPs, appears to be
      catalyzed by two biochemically distinct enzymes. However, only one of these two
      enzymes has been molecularly characterized. We now describe a novel class of
      phosphatidylinositol 4-kinases that probably corresponds to the missing element
      in phosphatidylinositol metabolism. These kinases are highly conserved
      evolutionarily, but unrelated to previously characterized phosphatidylinositol
      kinases, and thus represent the founding members of a new family. The novel
      phosphatidylinositol 4-kinases, which are widely expressed in cells, only
      phosphorylate phosphatidylinositol, are potently inhibited by adenosine, but are
      insensitive to wortmannin or phenylarsine oxide. Although they lack an obvious
      transmembrane domain, they are strongly attached to membranes by palmitoylation.
      Our data suggest that independent pathways for phosphatidylinositol 4-phosphate
      synthesis emerged during evolution, possibly to allow tight temporal and spatial
      control over the production of this key signaling molecule.

PMID- 11244088
TI  - The atypical protein kinase C-interacting protein p62 is a scaffold for NF-kappaB
      activation by nerve growth factor.
AB  - Nerve growth factor (NGF) binding to both p75 and TrkA neurotrophin receptors
      activates the transcription factor nuclear factor kappaB (NF-kappaB). Here we
      show that the atypical protein kinase C-interacting protein, p62, which binds
      TRAF6, selectively interacts with TrkA but not p75. In contrast, TRAF6 interacts
      with p75 but not TrkA. We demonstrate the formation of a TRAF6-p62 complex that
      serves as a bridge linking both p75 and TrkA signaling. Of functional relevance,
      transfection of antisense p62-enhanced p75-mediated cell death and diminished NGF
      induced differentiation occur through a mechanism involving inhibition of IKK
      activity. These findings reveal a new function for p62 as a common platform for
      communication of both p75-TRAF6 and TrkA signals. Moreover, we demonstrated that
      p62 serves as a scaffold for activation of the NF-kappaB pathway, which mediates
      NGF survival and differentiation responses.

PMID- 11244089
TI  - Altered quinone biosynthesis in the long-lived clk-1 mutants of Caenorhabditis
      elegans.
AB  - Mutations in the clk-1 gene of Caenorhabditis elegans result in an extended life
      span and an average slowing down of developmental and behavioral rates. However,
      it has not been possible to identify biochemical changes that might underlie the
      extension of life span observed in clk-1 mutants, and therefore the function of
      CLK-1 in C. elegans remains unknown. In this report, we analyzed the effect of
      clk-1 mutation on ubiquinone (UQ(9)) biosynthesis and show that clk-1 mutants
      mitochondria do not contain detectable levels of UQ(9). Instead, the UQ(9)
      biosynthesis intermediate, demethoxyubiquinone (DMQ(9)), is present at high
      levels. This result demonstrates that CLK-1 is absolutely required for the
      biosynthesis of UQ(9) in C. elegans. Interestingly, the activity levels of NADH
      cytochrome c reductase and succinate-cytochrome c reductase in mutant
      mitochondria are very similar to those in the wild-type, suggesting that DMQ(9)
      can function as an electron carrier in the respiratory chain. To test this
      possibility, the short side chain derivative DMQ(2) was chemically synthesized.
      We find that DMQ(2) can act as an electron acceptor for both complex I and
      complex II in clk-1 mutant mitochondria, while another ubiquinone biosynthesis
      precursor, 3-hydroxy-UQ(2), cannot. The accumulation of DMQ(9) and its use in
      mutant mitochondria indicate, for the first time in any organism, a link between
      the alteration in the quinone species used in respiration and life span.

PMID- 11244090
TI  - Alternative splicing switches potassium channel sensitivity to protein
      phosphorylation.
AB  - Alternative exon splicing and reversible protein phosphorylation of large
      conductance calcium-activated potassium (BK) channels represent fundamental
      control mechanisms for the regulation of cellular excitability. BK channels are
      encoded by a single gene that undergoes extensive, hormonally regulated exon
      splicing. In native tissues BK channels display considerable diversity and
      plasticity in their regulation by cAMP-dependent protein kinase (PKA).
      Differential regulation of alternatively spliced BK channels by PKA may provide a
      molecular basis for the diversity and plasticity of BK channel sensitivities to
      PKA. Here we demonstrate that PKA activates BK channels lacking splice inserts
      (ZERO) but inhibits channels expressing a 59-amino acid exon at splice site 2
      (STREX-1). Channel activation is dependent upon a conserved C-terminal PKA
      consensus motif (S869), whereas inhibition is mediated via a STREX-1 exon
      specific PKA consensus site. Thus, alternative splicing acts as a molecular
      switch to determine the sensitivity of potassium channels to protein
      phosphorylation.

PMID- 11244091
TI  - MEK7-dependent activation of p38 MAP kinase in keratinocytes.
AB  - Previous studies suggest that a PKC/Ras/MEKK1 cascade regulates involucrin (hINV)
      gene expression in human epidermal keratinocytes. MEK7, which is expressed in
      epidermis, has been identified as a member of this cascade (Efimova, T., LaCelle,
      P., Welter, J. F., and Eckert, R. L. (1998) J. Biol. Chem. 273, 24387-24395 and
      Efimova, T., and Eckert, R. L. (2000) J. Biol. Chem. 275, 1601-1607). However,
      the kinase that functions downstream of MEK7 has not been identified. Our present
      studies show that MEK7 expression in keratinocytes markedly activates p38alpha
      and modestly activates JNK. Activation of p38 MAPK by MEK7 is a novel finding, as
      previous reports have assigned MEK7 as a JNK regulator. We also demonstrate that
      this regulation is physiologically important, as the p38alpha- and JNK-dependent
      activities regulate hINV promoter activity and expression of the endogenous hINV
      gene.

PMID- 11244092
TI  - The Nedd4-like protein KIAA0439 is a potential regulator of the epithelial sodium
      channel.
AB  - The amiloride-sensitive epithelial sodium channel (ENaC) plays a critical role in
      fluid and electrolyte homeostasis and consists of alpha, beta, and gamma
      subunits. The carboxyl terminus of each ENaC subunit contains a PPxY, motif which
      is believed to be important for interaction with the WW domains of the ubiquitin
      protein ligase, Nedd4. Disruption of this interaction, as in Liddle's syndrome,
      where mutations delete or alter the PPxY motif of either the beta or gamma
      subunits, has been proposed to result in increased ENaC activity. Here we present
      evidence that KIAA0439 protein, a close relative of Nedd4, is also a potential
      regulator of ENaC. We demonstrate that KIAA0439 WW domains bind all three ENaC
      subunits. We show that a recombinant KIAA0439 WW domain protein acts as a
      dominant negative mutant that can interfere with the Na(+)-dependent feedback
      inhibition of ENaC in whole-cell patch clamp experiments. We propose that
      KIAA0439 and Nedd4 proteins either play a redundant role in ENaC regulation or
      function in a tissue- and/or signal-specific manner to down-regulate ENaC.

PMID- 11244093
TI  - Grasses. a collective model genetic system.

PMID- 11244094
TI  - Golden rice and beyond.

PMID- 11244095
TI  - The use of the Monsanto draft rice genome sequence in research.

PMID- 11244096
TI  - Rice bioinformatics. analysis of rice sequence data and leveraging the data to
      other plant species.
AB  - Rice (Oryza sativa) is a model species for monocotyledonous plants, especially
      for members in the grass family. Several attributes such as small genome size,
      diploid nature, transformability, and establishment of genetic and molecular
      resources make it a tractable organism for plant biologists. With an estimated
      genome size of 430 Mb (Arumuganathan and Earle, 1991), it is feasible to obtain
      the complete genome sequence of rice using current technologies. An international
      effort has been established and is in the process of sequencing O. sativa spp.
      japonica var "Nipponbare" using a bacterial artificial chromosome/P1 artificial
      chromosome shotgun sequencing strategy. Annotation of the rice genome is
      performed using prediction-based and homology-based searches to identify genes.
      Annotation tools such as optimized gene prediction programs are being developed
      for rice to improve the quality of annotation. Resources are also being developed
      to leverage the rice genome sequence to partial genome projects such as expressed
      sequence tag projects, thereby maximizing the output from the rice genome
      project. To provide a low level of annotation for rice genomic sequences, we have
      aligned all rice bacterial artificial chromosome/P1 artificial chromosome
      sequences with The Institute of Genomic Research Gene Indices that are a set of
      nonredundant transcripts that are generated from nine public plant expressed
      sequence tag projects (rice, wheat, sorghum, maize, barley, Arabidopsis, tomato,
      potato, and barrel medic). In addition, we have used data from The Institute of
      Genomic Research Gene Indices and the Arabidopsis and Rice Genome Projects to
      identify putative orthologues and paralogues among these nine genomes.

PMID- 11244097
TI  - Transposon insertional mutagenesis in rice.

PMID- 11244098
TI  - Retrobiosynthetic nuclear magnetic resonance analysis of amino acid biosynthesis
      and intermediary metabolism. Metabolic flux in developing maize kernels.
AB  - Information on metabolic networks could provide the basis for the design of
      targets for metabolic engineering. To study metabolic flux in cereals, developing
      maize (Zea mays) kernels were grown in sterile culture on medium containing [U
      (13)C(6)]glucose or [1,2-(13)C(2)]acetate. After growth, amino acids, lipids, and
      sitosterol were isolated from kernels as well as from the cobs, and their (13)C
      isotopomer compositions were determined by quantitative nuclear magnetic
      resonance spectroscopy. The highly specific labeling patterns were used to
      analyze the metabolic pathways leading to amino acids and the triterpene on a
      quantitative basis. The data show that serine is generated from phosphoglycerate,
      as well as from glycine. Lysine is formed entirely via the diaminopimelate
      pathway and sitosterol is synthesized entirely via the mevalonate route. The
      labeling data of amino acids and sitosterol were used to reconstruct the labeling
      patterns of key metabolic intermediates (e.g. acetyl-coenzyme A, pyruvate,
      phosphoenolpyruvate, erythrose 4-phosphate, and Rib 5-phosphate) that revealed
      quantitative information about carbon flux in the intermediary metabolism of
      developing maize kernels. Exogenous acetate served as an efficient precursor of
      sitosterol, as well as of amino acids of the aspartate and glutamate family; in
      comparison, metabolites formed in the plastidic compartments showed low acetate
      incorporation.

PMID- 11244099
TI  - Cleavage of bipartite substrates by rice and maize ribonuclease P. Application to
      degradation of target mRNAs in plants.

PMID- 11244100
TI  - Grasses as a single genetic system: reassessment 2001.

PMID- 11244101
TI  - Evolutionary history of the grasses.

PMID- 11244102
TI  - Aquaporins constitute a large and highly divergent protein family in maize.
AB  - Aquaporins (AQPs) are an ancient family of channel proteins that transport water
      and neutral solutes through a pore and are found in all eukaryotes and most
      prokaryotes. A comparison of the amino acid sequences and phylogenetic analysis
      of 31 full-length cDNAs of maize (Zea mays) AQPs shows that they comprise four
      different groups of highly divergent proteins. We have classified them as plasma
      membrane intinsic proteins (PIPs), tonoplast intrinsic proteins, Nod26-like
      intrinsic proteins, and small and basic intrinsic proteins. Amino acid sequence
      identities vary from 16% to 100%, but all sequences share structural motifs and
      conserved amino acids necessary to stabilize the two loops that form the aqueous
      pore. Most divergent are the small and basic integral proteins in which the first
      of the two highly conserved Asn-Pro-Ala motifs of the pore is not conserved, but
      is represented by alanine-proline-threonine or alanine-proline-serine. We present
      a model of ZmPIP1-2 based on the three-dimensional structure of mammalian AQP1.
      Tabulation of the number of times that the AQP sequences are found in a
      collection of databases that comprises about 470,000 maize cDNAs indicates that a
      few of the maize AQPs are very highly expressed and many are not abundantly
      expressed. The phylogenetic analysis supports the interpretation that the
      divergence of PIPs through gene duplication occurred more recently than the
      divergence of the members of the other three subfamilies. This study opens the
      way to analyze the function of the proteins in Xenopus laevis oocytes, determine
      the tissue specific expression of the genes, recover insertion mutants, and
      determine the in planta function.

PMID- 11244103
TI  - A complete set of maize individual chromosome additions to the oat genome.
AB  - All 10 chromosomes of maize (Zea mays, 2n = 2x = 20) were recovered as single
      additions to the haploid complement of oat (Avena sativa, 2n = 6x = 42) among
      F(1) plants generated from crosses involving three different lines of maize to
      eight different lines of oat. In vitro rescue culture of more than 4,300 immature
      F(1) embryos resulted in a germination frequency of 11% with recovery of 379 F(1)
      plantlets (8.7%) of moderately vigorous growth. Some F(1) plants were sectored
      with distinct chromosome constitutions among tillers of the same plant and also
      between root and shoot cells. Meiotic restitution facilitated development of un
      reduced gametes in the F(1). Self-pollination of these partially fertile F(1)
      plants resulted in disomic additions (2n = 6x + 2 = 44) for maize chromosomes 1,
      2, 3, 4, 6, 7, and 9. Maize chromosome 8 was recovered as a monosomic addition
      (2n = 6x + 1 = 43). Monosomic additions for maize chromosomes 5 and 10 to a
      haploid complement of oat (n = 3x + 1 = 22) were recovered several times among
      the F(1) plants. Although partially fertile, these chromosome 5 and 10 addition
      plants have not yet transmitted the added maize chromosome to F(2) offspring. We
      discuss the development and general utility of this set of oat-maize addition
      lines as a novel tool for maize genomics and genetics.

PMID- 11244104
TI  - Mapping maize sequences to chromosomes using oat-maize chromosome addition
      materials.
AB  - Oat- (Avena sativa) maize (Zea mays) chromosome additions are produced by
      crossing maize and oat. During early embryo development maize chromosomes are
      preferentially eliminated, and oat plants are often recovered that retain a
      single maize chromosome. Each of the 10 maize chromosomes recently has been
      isolated as a separate oat-maize addition. We describe here the mapping of 400
      maize sequences to chromosomes using polymerase chain reaction and DNA from the
      oat-maize addition material. Fifty of the sequences were from cloned markers that
      had been previously mapped by linkage analysis, and our results were consistent
      with those obtained using Southern-blot analysis. Previously unmapped expressed
      sequence tags and sequence tagged sites (350) were mapped to chromosomes. Maize
      gene sequences and expression data are rapidly being accumulated. Coupling this
      information with positional information from high throughput mapping programs
      provides plant biologists powerful tools for identifying candidate genes of
      interest.

PMID- 11244105
TI  - Sequence haplotypes revealed by sequence-tagged site fine mapping of the Ror1
      gene in the centromeric region of barley chromosome 1H.
AB  - We describe the development of polymerase chain reaction-based, sequence-tagged
      site (STS) markers for fine mapping of the barley (Hordeum vulgare) Ror1 gene
      required for broad-spectrum resistance to powdery mildew (Blumeria graminis f.
      sp. hordei). After locating Ror1 to the centromeric region of barley chromosome
      1H using a combined amplified fragment length polymorphism/restriction fragment
      length polymorphism (RFLP) approach, sequences of RFLP probes from this
      chromosome region of barley and corresponding genome regions from the related
      grass species oat (Avena spp.), wheat, and Triticum monococcum were used to
      develop STS markers. Primers based on the RFLP probe sequences were used to
      polymerase chain reaction-amplify and directly sequence homologous DNA stretches
      from each of four parents that were used for mapping. Over 28,000 bp from 22
      markers were compared. In addition to one insertion/deletion of at least 2.0 kb,
      79 small unique sequence polymorphisms were observed, including 65 single
      nucleotide substitutions, two dinucleotide substitutions, 11 insertion/deletions,
      and one 5-bp/10-bp exchange. The frequency of polymorphism between any two barley
      lines ranged from 0.9 to 3.0 kb, and was greatest for comparisons involving an
      Ethiopian landrace. Haplotype structure was observed in the marker sequences over
      distances of several hundred basepairs. Polymorphisms in 16 STSs were used to
      generate genetic markers, scored by restriction enzyme digestion or by direct
      sequencing. Over 2,300 segregants from three populations were used in Ror1
      linkage analysis, mapping Ror1 to a 0.2- to 0.5-cM marker interval. We discuss
      the implications of sequence haplotypes and STS markers for the generation of
      high-density maps in cereals.

PMID- 11244106
TI  - Screening of the rice viviparous mutants generated by endogenous retrotransposon
      Tos17 insertion. Tagging of a zeaxanthin epoxidase gene and a novel ostatc gene.
AB  - The rice (Oryza sativa) retrotransposon Tos17 is one of a few active
      retrotransposons in plants and its transposition is activated by tissue culture.
      Here, we present the characterization of viviparous mutants of rice induced by
      tissue culture to demonstrate the feasibility of the use of retrotransposon Tos17
      as an endogenous insertional mutagen and cloning of the tagged gene for forward
      genetics in unraveling the gene function. Two mutants were shown to be caused by
      the insertion of Tos17. Osaba1, a strong viviparous mutant with wilty phenotype,
      displayed low abscisic acid level and almost no further increase in its levels
      upon drought. The mutant is shown to be impaired in the epoxidation of
      zeaxanthin. On the other hand, Ostatc, a mutant with weak phenotype, exhibited
      the pale green phenotype and slight increase in abscisic acid levels upon
      drought. Deduced amino acids of the causative genes of Osaba1 and Ostatc
      manifested a significantly high homology with zeaxanthin epoxidase isolated from
      other plant species and with bacterial Sec-independent translocase TATC protein,
      respectively. This is the first example of transposon tagging in rice.

PMID- 11244107
TI  - Towards a better understanding of the genetic and physiological basis for
      nitrogen use efficiency in maize.
AB  - To enhance our understanding of the genetic basis of nitrogen use efficiency in
      maize (Zea mays), we have developed a quantitative genetic approach by
      associating metabolic functions and agronomic traits to DNA markers. In this
      study, leaves of vegetative recombinant inbred lines of maize, already assessed
      for their agronomic performance, were analyzed for physiological traits such as
      nitrate content, nitrate reductase (NR), and glutamine synthetase (GS)
      activities. A significant genotypic variation was found for these traits and a
      positive correlation was observed between nitrate content, GS activity and yield,
      and its components. NR activity, on the other hand, was negatively correlated.
      These results suggest that increased productivity in maize genotypes was due to
      their ability to accumulate nitrate in their leaves during vegetative growth and
      to efficiently remobilize this stored nitrogen during grain filling. Quantitative
      trait loci (QTL) for various agronomic and physiological traits were searched for
      and located on the genetic map of maize. Coincidences of QTL for yield and its
      components with genes encoding cytosolic GS and the corresponding enzyme activity
      were detected. In particular, it appears that the GS locus on chromosome 5 is a
      good candidate gene that can, at least partially, explain variations in yield or
      kernel weight. Because at this locus coincidences of QTLs for grain yield, GS, NR
      activity, and nitrate content were also observed, we hypothesize that leaf
      nitrate accumulation and the reactions catalyzed by NR and GS are coregulated and
      represent key elements controlling nitrogen use efficiency in maize.

PMID- 11244108
TI  - Quantitative trait locus mapping of loci influencing elongation factor 1alpha
      content in maize endosperm.
AB  - The nutritional value of maize (Zea mays) seed is most limited by its protein
      quality because its storage proteins are devoid of the essential amino acid
      lysine (Lys). The Lys content of the kernel can be significantly increased by the
      opaque-2 mutation, which reduces zein synthesis and increases accumulation of
      proteins that contain Lys. Elongation factor 1alpha (eEF1A) is one of these
      proteins, and its concentration is highly correlated with the Lys content of the
      endosperm. We investigated the genetic regulation of eEF1A and the basis for its
      relationship with other Lys-containing proteins by analyzing the progeny of a
      cross between a high (Oh51Ao2) and a low (Oh545o2) eEF1A maize inbred. We
      identified 83 simple sequence repeat loci that are polymorphic between these
      inbreds; the markers are broadly distributed over the genome (1,402 cM) with an
      average interval of 17 cM. Genotypic analysis of the F(2) progeny revealed two
      significant quantitative trait loci that account for 25% of the variance for
      eEF1A content. One of these is on the short arm of chromosome 4 and is linked
      with a cluster of 22-kD alpha-zein coding sequences; the other quantitative trait
      locus is on the long arm of chromosome 7. The content of alpha-zein and gamma
      zein was measured in pools of high- and low-eEF1A individuals obtained from this
      cross, and a higher level of alpha-zein was found to cosegregate with high eEF1A
      content. Allelic variation at the 22-kD alpha-zein locus may contribute to the
      difference of eEF1A content between Oh51Ao2 and Oh545o2 by increasing the surface
      area of protein bodies in the endosperm and creating a more extensive network of
      cytoskeletal proteins.

PMID- 11244109
TI  - Active retrotransposons are a common feature of grass genomes.
AB  - A large fraction of the genomes of grasses, members of the family Graminae, is
      composed of retrotransposons. These elements resemble animal retroviruses in
      their structure and possess a life cycle similar to theirs that includes
      transcription, translation, and integration of daughter copies. We have
      investigated if retrotransposons are generally transcribed in the grasses and
      other plants, and whether the various families of elements are translationally
      and integrationally active in multiple grass species. A systematic search of 7.8
      x 10(5) publicly available expressed sequence tags from plants revealed
      widespread retrotransposon transcripts at a frequency of one in 1,000. Monocot
      retrotransposons found relatively more expressed sequence tags from non-source
      species than did those of dicots. Antibodies were raised to the capsid protein,
      GAG, of BARE-1, a transcribed and translated copia-like retrotransposon of barley
      (Hordeum vulgare). These detected immunoreactive proteins of sizes identical to
      those of the BARE-1 GAG and polyprotein, respectively, in other species of the
      tribe Triticeae as well as in oats (Avena sativa) and rice (Oryza sativa).
      Retrotransposon-based markers showed integrational polymorphisms for BARE-1 in
      different subfamilies of the Graminae. The results suggest that grasses share
      families of transcriptionally, translationally, and integrationally active
      retrotransposons, enabling a comparative and integrative approach to
      understanding the life cycle of retrotransposons and their impact on the genome.

PMID- 11244110
TI  - Mutator transposase is widespread in the grasses.
AB  - Although the Mutator (Mu) system is well characterized in maize (Zea mays), very
      little is known about this highly mutagenic system of transposons in other
      grasses. Mutator is regulated by the MuDR class of elements, which encodes two
      genes, one of which, mudrA, has similarity to a number of bacterial transposases.
      Experiments in our laboratory, as well as database searches, demonstrate that
      mudrA sequences are ubiquitous and diverse in the grasses. In several species it
      is clear that multiple paralogous elements can be present in a single genome. In
      some species such as wheat (Triticum aestivum) and rice (Oryza sativa), mudrA
      similar sequences are represented in cDNA databases, suggesting the presence of
      active Mu transposon systems in these species. Further, in rice and in sorghum,
      mudrA-like genes are flanked by long terminal inverted repeats, as well as the
      short host sequence direct repeats diagnostic of insertion. Thus, there is ample
      evidence that systems related to Mu in maize are at least potentially active in a
      wide variety of grasses. However, the mudrB gene, though important for Mu
      activity in maize, is not necessarily a component of Mu elements in other
      grasses.

PMID- 11244111
TI  - Molecular evolution of receptor-like kinase genes in hexaploid wheat. Independent
      evolution of orthologs after polyploidization and mechanisms of local
      rearrangements at paralogous loci.
AB  - Hexaploid wheat is a young polyploid species and represents a good model to study
      mechanisms of gene evolution after polyploidization. Recent studies at the scale
      of the whole genome have suggested rapid genomic changes after polyploidization
      but so far the rearrangements that have occurred in terms of gene content and
      organization have not been analyzed at the microlevel in wheat. Here, we have
      isolated members of a receptor kinase (Lrk) gene family in hexaploid and diploid
      wheat, Aegilops tauschii, and barley (Hordeum vulgare). Phylogenetic analysis has
      allowed us to establish evolutionary relationships (orthology versus paralogy)
      between the different members of this gene family in wheat as well as with Lrk
      genes from barley. It also demonstrated that the sequences of the homoeologous
      Lrk genes evolved independently after polyploidization. In addition, we found
      evidence for gene loss during the evolution of wheat and barley. Analysis of
      large genomic fragments isolated from nonorthologous Lrk loci showed a high
      conservation of the gene content and gene organization at these loci on the
      homoeologous group 1 chromosomes of wheat and barley. Finally, sequence
      comparison of two paralogous fragments of chromosome 1B showed a large number of
      local events (sequence duplications, deletions, and insertions), which reveal
      rearrangements and mechanisms for genome enlargement at the microlevel.

PMID- 11244112
TI  - Comparison of starch-branching enzyme genes reveals evolutionary relationships
      among isoforms. Characterization of a gene for starch-branching enzyme IIa from
      the wheat genome donor Aegilops tauschii.
AB  - Genes and cDNAs for starch-branching enzyme II (SBEII) have been isolated from
      libraries constructed from Aegilops tauschii and wheat (Triticum aestivum)
      endosperm, respectively. One class of genes has been termed wSBEII-DA1 and
      encodes the N terminus reported for an SBEII from wheat endosperm. On the basis
      of phylogenetic comparisons with other branching enzyme sequences, wSBEII-DA1 is
      considered to be a member of the SBEIIa class. The wSBEII-DA1 gene consists of 22
      exons with exons 4 to 21 being identical in length to the maize (Zea mays) SBEIIb
      gene, and the gene is located in the proximal region of the long arm of
      chromosome 2 at a locus designated sbe2a. RNA encoding SBEIIa can be detected in
      the endosperm from 6 d after flowering and is at its maximum level from 15 to 18
      d after anthesis. Use of antibodies specific for SBEIIa demonstrated that this
      protein was present in both the soluble and granule bound fractions in developing
      wheat endosperm. We also report a cDNA sequence for SBEIIa that could arise by
      variant transcription/splicing. A second gene, termed wSBEII-DB1, was isolated
      and encodes an SBEII, which shows greater sequence identity with SBEIIb-type
      sequences than with SBEIIa-type sequences. Comparisons of SBEII gene structures
      among wheat, maize, and Arabidopsis indicate the lineage of the SBEII genes.

PMID- 11244113
TI  - Toward integration of comparative genetic, physical, diversity, and cytomolecular
      maps for grasses and grains, using the sorghum genome as a foundation.
AB  - The small genome of sorghum (Sorghum bicolor L. Moench.) provides an important
      template for study of closely related large-genome crops such as maize (Zea mays)
      and sugarcane (Saccharum spp.), and is a logical complement to distantly related
      rice (Oryza sativa) as a "grass genome model." Using a high-density RFLP map as a
      framework, a robust physical map of sorghum is being assembled by integrating
      hybridization and fingerprint data with comparative data from related taxa such
      as rice and using new methods to resolve genomic duplications into locus-specific
      groups. By taking advantage of allelic variation revealed by heterologous probes,
      the positions of corresponding loci on the wheat (Triticum aestivum), rice,
      maize, sugarcane, and Arabidopsis genomes are being interpolated on the sorghum
      physical map. Bacterial artificial chromosomes for the small genome of rice are
      shown to close several gaps in the sorghum contigs; the emerging rice physical
      map and assembled sequence will further accelerate progress. An important
      motivation for developing genomic tools is to relate molecular level variation to
      phenotypic diversity. "Diversity maps," which depict the levels and patterns of
      variation in different gene pools, shed light on relationships of allelic
      diversity with chromosome organization, and suggest possible locations of genomic
      regions that are under selection due to major gene effects (some of which may be
      revealed by quantitative trait locus mapping). Both physical maps and diversity
      maps suggest interesting features that may be integrally related to the
      chromosomal context of DNA-progress in cytology promises to provide a means to
      elucidate such relationships. We seek to provide a detailed picture of the
      structure, function, and evolution of the genome of sorghum and its relatives,
      together with molecular tools such as locus-specific sequence-tagged site DNA
      markers and bacterial artificial chromosome contigs that will have enduring value
      for many aspects of genome analysis.

PMID- 11244114
TI  - Comparative sequence analysis of colinear barley and rice bacterial artificial
      chromosomes.
AB  - Colinearity of a large region from barley (Hordeum vulgare) chromosome 5H and
      rice (Oryza sativa) chromosome 3 has been demonstrated by mapping of several
      common restriction fragment-length polymorphism clones on both regions. One of
      these clones, WG644, was hybridized to rice and barley bacterial artificial
      chromosome (BAC) libraries to select homologous clones. One BAC from each species
      with the largest overlapping segment was selected by fingerprinting and blot
      hybridization with three additional restriction fragment-length polymorphism
      clones. The complete barley BAC 635P2 and a 50-kb segment of the rice BAC 36I5
      were completely sequenced. A comparison of the rice and barley DNA sequences
      revealed the presence of four conserved regions, containing four predicted genes.
      The four genes are in the same orientation in rice, but the second gene is in
      inverted orientation in barley. The fourth gene is duplicated in tandem in barley
      but not in rice. Comparison of the homeologous barley and rice sequences assisted
      the gene identification process and helped determine individual gene structures.
      General gene structure (exon number, size, and location) was largely conserved
      between rice and barley and to a lesser extent with homologous genes in
      Arabidopsis. Colinearity of these four genes is not conserved in Arabidopsis
      compared with the two grass species. Extensive similarity was not found between
      the rice and barley sequences other than within the exons of the structural
      genes, and short stretches of homology in the promoters and 3' untranslated
      regions. The larger distances between the first three genes in barley compared
      with rice are explained by the insertion of different transposable retroelements.

PMID- 11244115
TI  - Transposon-mediated single-copy gene delivery leads to increased transgene
      expression stability in barley.
AB  - Instability of transgene expression in plants is often associated with complex
      multicopy patterns of transgene integration at the same locus, as well as
      position effects due to random integration. Based on maize transposable elements
      Activator (Ac) and Dissociation (Ds), we developed a method to generate large
      numbers of transgenic barley (Hordeum vulgare var Golden Promise) plants, each
      carrying a single transgene copy at different locations. Plants expressing Ac
      transposase (AcTPase) were crossed with plants containing one or more copies of
      bar, a selectable herbicide (Basta) resistance gene, located between inverted
      repeat Ds ends (Ds-bar). F(1) plants were self-pollinated and the F(2) generation
      was analyzed to identify plants segregating for transposed Ds-bar elements. Of Ds
      bar transpositions, 25% were in unlinked sites that segregated from vector
      sequences, other Ds-bar copies, and the AcTPase gene, resulting in numerous
      single-copy Ds-bar plants carrying the transgene at different locations.
      Transgene expression in F(2) plants with transposed Ds-bar was 100% stable,
      whereas only 23% of F(2) plants carrying Ds-bar at the original site expressed
      the transgene product stably. In F(3) and F(4) populations, transgene expression
      in 81.5% of plants from progeny of F(2) plants with single-copy, transposed Ds
      bar remained completely stable. Analysis of the integration site in single-copy
      plants showed that transposed Ds-bar inserted into single- or low-copy regions of
      the genome, whereas silenced Ds-bar elements at their original location were
      inserted into redundant or highly repetitive genomic regions. Methylation of the
      non-transposed transgene and its promoter, as well as a higher condensation of
      the chromatin around the original integration site, was associated with plants
      exhibiting transgene silencing.

PMID- 11244116
TI  - B-Bolivia, an allele of the maize b1 gene with variable expression, contains a
      high copy retrotransposon-related sequence immediately upstream.
AB  - The maize (Zea mays) b1 gene encodes a transcription factor that regulates the
      anthocyanin pigment pathway. Of the b1 alleles with distinct tissue-specific
      expression, B-Peru and B-Bolivia are the only alleles that confer seed
      pigmentation. B-Bolivia produces variable and weaker seed expression but darker,
      more regular plant expression relative to B-Peru. Our experiments demonstrated
      that B-Bolivia is not expressed in the seed when transmitted through the male.
      When transmitted through the female the proportion of kernels pigmented and the
      intensity of pigment varied. Molecular characterization of B-Bolivia demonstrated
      that it shares the first 530 bp of the upstream region with B-Peru, a region
      sufficient for seed expression. Immediately upstream of 530 bp, B-Bolivia is
      completely divergent from B-Peru. These sequences share sequence similarity to
      retrotransposons. Transient expression assays of various promoter constructs
      identified a 33-bp region in B-Bolivia that can account for the reduced aleurone
      pigment amounts (40%) observed with B-Bolivia relative to B-Peru. Transgenic
      plants carrying the B-Bolivia promoter proximal region produced pigmented seeds.
      Similar to native B-Bolivia, some transgene loci are variably expressed in seeds.
      In contrast to native B-Bolivia, the transgene loci are expressed in seeds when
      transmitted through both the male and female. Some transgenic lines produced
      pigment in vegetative tissues, but the tissue-specificity was different from B
      Bolivia, suggesting the introduced sequences do not contain the B-Bolivia plant
      specific regulatory sequences. We hypothesize that the chromatin context of the B
      Bolivia allele controls its epigenetic seed expression properties, which could be
      influenced by the adjacent highly repeated retrotransposon sequence.

PMID- 11244117
TI  - Role of mRNA secondary structure in translational repression of the maize
      transcriptional activator Lc(1,2).
AB  - Lc, a member of the maize (Zea mays) R/B gene family, encodes a basic helix-loop
      helix transcriptional activator of the anthocyanin biosynthetic pathway. It was
      previously shown that translation of the Lc mRNA is repressed by a 38-codon
      upstream open reading frame (uORF) in the 5' leader. In this study, we report
      that a potential hairpin structure near the 5'end of the Lc mRNA also represses
      downstream translation in the rabbit reticulocyte in vitro translation system and
      in transient transformation assays. Base pairing of the hairpin is important for
      repression because its destabilization increases translation of the uORF and the
      downstream ORF. However, translation of the uORF is not required for the hairpin
      mediated repression. Instead, the uORF and the 5'-proximal hairpin mediate two
      independent levels of repression. Although the uORF represses downstream
      translation due to inefficient reinitiation of ribosomes that translate uORF, the
      hairpin inhibits ribosome loading at the 5' end of the mRNA.

PMID- 11244119
TI  - Identification of Mutator insertional mutants of starch-branching enzyme 2a in
      corn.
AB  - Starch-branching enzymes (SBE) break the alpha-1,4 linkage of starch, re
      attaching the chain to a glucan chain by an alpha-1,6 bond, altering starch
      structure. SBEs also facilitate starch accumulation by increasing the number of
      non-reducing ends on the growing chain. In maize (Zea mays), three isoforms of
      SBE have been identified. To examine the function of the SBEIIa isoform, a
      reverse genetics polymerase chain reaction-based screen was used to identify a
      mutant line segregating for a Mutator transposon within Sbe2a. To locate the
      insertion within the second exon of Sbe2a, the genomic sequence of Sbe2a
      containing the promoter and 5' end was isolated and sequenced. Plants homozygous
      for sbe2a::Mu have undetectable levels of Sbe2a transcripts and SBEIIa in their
      leaves. Characterization of leaf starch from sbe2a::Mu mutants shows reduced
      branching similar to yet more extreme than that seen in kernels lacking SBEIIb
      activity. Characterization of endosperm starch from sbe2a::Mu mutants shows
      branching that is indistinguishable from wild-type controls. These mutant plants
      have a visible phenotype resembling accelerated senescence, which was correlated
      with the Mutator insertion within Sbe2a. This correlation suggests a specific
      role for SBEIIa in leaves, which may be necessary for normal plant development.

PMID- 11244118
TI  - Nonsense-mediated decay of mutant waxy mRNA in rice.
AB  - Two rice (Oryza sativa) waxy mutations of the Japonica background were shown to
      contain approximately 20% of the fully spliced mRNA relative to the wild type.
      Sequencing analysis of the entire waxy genes of the two mutants revealed the
      presence of premature translation termination codons in exon 2 and exon 7. These
      results indicated that the lower accumulation of fully spliced RNA in the mutants
      was caused by nonsense-mediated decay (NMD), which is an RNA surveillance system
      universally found in eukaryotes. It is interesting that levels of RNA retaining
      intron 1 were not changed by premature nonsense codons, suggesting that splicing
      may be linked with NMD in plants, as previously found in mammalian cells.
      Measurements of the half-lives of waxy RNAs in transfected rice protoplasts
      indicated that the half-life of waxy RNA with a premature nonsense codon was 3.3
      times shorter than that without a premature nonsense codon. Because the wild-type
      waxy transcripts, which are derived from the Wx(b) gene predominantly distributed
      among Japonica rice, have been shown to be less efficiently spliced and their
      alternative splicing has been documented, we examined whether these splicing
      properties influenced the efficiency of NMD. However, no effects were observed.
      These results established that NMD occurs in rice waxy RNA containing a premature
      nonsense codon.

PMID- 11244120
TI  - Molecular structure of three mutations at the maize sugary1 locus and their
      allele-specific phenotypic effects.
AB  - Starch production in all plants examined is altered by mutations of isoamylase
      type starch-debranching enzymes (DBE), although how these proteins affect glucan
      polymer assembly is not understood. Various allelic mutations in the maize (Zea
      mays) gene sugary1 (su1), which codes for an isoamylase-type DBE, condition
      distinct kernel phenotypes. This study characterized the recessive mutations su1
      Ref, su1-R4582::Mu1, and su1-st, regarding their molecular basis, chemical
      phenotypes, and effects on starch metabolizing enzymes. The su1-Ref allele
      results in two specific amino acid substitutions without affecting the Su1 mRNA
      level. The su1-R4582::Mu1 mutation is a null allele that abolishes transcript
      accumulation. The su1-st mutation results from insertion of a novel transposon
      like sequence, designated Toad, which causes alternative pre-mRNA splicing. Three
      su1-st mutant transcripts are produced, one that is nonfunctional and two that
      code for modified SU1 polypeptides. The su1-st mutation is dominant to the null
      allele su1-R4582::Mu1, but recessive to su1-Ref, suggestive of complex effects
      involving quaternary structure of the SU1 enzyme. All three su1- alleles severely
      reduce or eliminate isoamylase-type DBE activity, although su1-st kernels
      accumulate less phytoglycogen and Suc than su1-Ref or su1-R4582::Mu1 mutants. The
      chain length distribution of residual amylopectin is significantly altered by su1
      Ref and su1-R4582::Mu1, whereas su1-st has modest effects. These results,
      together with su1 allele-specific effects on other starch- metabolizing enzymes
      detected in zymograms, suggest that total DBE catalytic activity is the not the
      sole determinant of Su1 function and that specific interactions between SU1 and
      other components of the starch biosynthetic system are required.

PMID- 11244121
TI  - Salinity-induced inhibition of leaf elongation in maize is not mediated by
      changes in cell wall acidification capacity.
AB  - The physiological mechanisms underlying leaf growth inhibition under salt stress
      are not fully understood. Apoplastic pH is considered to play an important role
      in cell wall loosening and tissue growth and was demonstrated to be altered by
      several growth-limiting environmental conditions. In this study we have evaluated
      the possibility that inhibition of maize (Zea mays) leaf elongation by salinity
      is mediated by changes in growing cell wall acidification capacity. The kinetics
      of extended apoplast pH changes by leaf tissue of known expansion rates and
      extent of growth reduction under stress was investigated (in vivo) and was found
      similar for non-stressed and salt-stressed tissues at all examined apoplast
      salinity levels (0.1, 5, 10, or 25 mM NaCl). A similar rate of spontaneous
      acidification for the salt and control treatments was demonstrated also in in
      situ experiments. Unlike growing cells that acidified the external medium, mature
      nongrowing cells caused medium alkalinization. The kinetics of pH changes by
      mature tissue was also unchanged by salt stress. Fusicoccin, an enhancer of
      plasmalemma H(+)-ATPase activity level, greatly stimulated elongation growth and
      acidification rate to a similar extent in the control and salt treatments. That
      the ability of the growing tissue to acidify the apoplast did not change under
      same salt stress conditions that induced inhibition of tissue elongation rate
      suggests that salinity does not inhibit cell growth by impairing the
      acidification process or reducing the inherent capacity for cell wall
      acidification.

PMID- 11244122
TI  - The salt stress-inducible protein kinase gene, Esi47, from the salt-tolerant
      wheatgrass Lophopyrum elongatum is involved in plant hormone signaling.
AB  - Protein kinases play a central role in signal transduction in all organisms and
      to study signal transduction in response to salt stress we have identified and
      characterized a gene encoding a protein kinase that is induced by salt stress and
      abscisic acid (ABA) in the salt-tolerant wild wheatgrass Lophopyrum elongatum
      (Host) A. Love. The product of the early salt stress-induced gene, Esi47, was
      found to belong to the "novel Arabidopsis protein kinase" group of plant
      serine/threonine protein kinases. Transient gene expression assays in barley
      aleurone tissue showed Esi47 to suppress the gibberellin induction of the barley
      low-pI alpha-amylase gene promoter, thus providing evidence for the role of this
      protein kinase gene in plant hormone signaling. Esi47 contains a small upstream
      open reading frame in the 5'-untranslated region of its transcript that is
      implicated in mediating the repression of the basal level of the gene expression
      and in regulating the ABA inducibility of the gene, as shown in the transient
      gene expression assay in maize callus. Three Arabidopsis homologs of Esi47 were
      identified, and different members of this clade of genes showed differential
      patterns of regulation by salt stress and ABA in Arabidopsis roots and leaves. At
      least one of the Arabidopsis homologs contains a small open reading frame in its
      5'-untranslated region, indicating that the unusual regulatory mechanism
      identified in Esi47 may be widely conserved.

PMID- 11244123
TI  - A rice membrane-bound calcium-dependent protein kinase is activated in response
      to low temperature.
AB  - Calcium-dependent protein kinases (CDPKs) are found in various subcellular
      localizations, which suggests that this family of serine/threonine kinases may be
      involved in multiple signal transduction pathways. CDPKs are believed to be
      involved in the response of plants to low temperatures, but the precise role in
      the signal transduction pathway is largely unknown. Previous reports described
      changes in CDPKs' mRNA levels in response to cold treatment, but whether these
      changes are accompanied by increases in protein level and/or kinase activities is
      unknown. In the present study, we identify in rice (Oryza sativa L. cv Don Juan)
      plants a 56-kD membrane-bound CDPK that is activated in response to cold
      treatment. Immunoblot analysis of the enzyme preparations from control and cold
      treated plants showed that the kinase level was similar in both preparations.
      However, both kinase and autophosphorylating activities of the enzyme prepared
      from cold-treated plants were significantly higher than that obtained from
      control plants. The activation of the CDPK is detected after 12 to 18 h of cold
      treatment, which indicates that the kinase does not participate in the initial
      response to low temperature but in the adaptative process to adverse conditions.
      To our knowledge, this is the first demonstration of a CDPK that is
      posttranscriptionally activated in response to low temperature.

PMID- 11244124
TI  - Hydrogen peroxide mediates the induction of chloroplastic Ndh complex under
      photooxidative stress in barley.
AB  - Chloroplast-encoded NDH polypeptides (components of the plastid Ndh complex) and
      the NADH dehydrogenase activity of the Ndh complex (NADH-DH) increased under
      photooxidative stress. The possible involvement of H2O2-mediated signaling in the
      photooxidative induction of chloroplastic ndh genes was thoroughly studied. We
      have analyzed the changes in the NADH-DH and steady-state levels of NDH-F
      polypeptide and ndhB and ndhF transcripts in barley (Hordeum vulgare cv Hassan)
      leaves. Subapical leaf segments were incubated in growing light (GL),
      photooxidative light (PhL), GL and H2O2 (GL + H2O2), or PhL and 50 nM paraquat in
      the incubation medium. Treatments with H2O2 under GL mimicked the photooxidative
      stimulus, causing a dose-dependent increase of NADH-DH and NDH-F polypeptide. The
      kinetic of Ndh complex induction was further studied in leaves pre-incubated with
      or without the H2O2-scavenger dimethyltiourea. NADH-DH and NDH-F polypeptide
      rapidly increased up to 16 h in PhL, GL+ H2O2, and, at higher rate, in PhL and
      paraquat. The observed increases of NADH-DH and NDH-F after 4 h in PhL and GL +
      H2O2 were not accompanied by significant changes in ndhB and ndhF transcripts.
      However, at 16-h incubations NADH-DH and NDH-F changes closely correlated with
      higher ndhB and ndhF transcript levels. All these effects were prevented by
      dimethylthiourea. It is proposed that the induction of chloroplastic ndh genes
      under photooxidative stress is mediated by H2O2 through mechanisms that involve a
      rapid translation of pre-existing transcripts and the increase of the ndh
      transcript levels.

PMID- 11244125
TI  - Malate-permeable channels and cation channels activated by aluminum in the apical
      cells of wheat roots.
AB  - Aluminum (Al(3+))-dependent efflux of malate from root apices is a mechanism for
      Al(3+) tolerance in wheat (Triticum aestivum). The malate anions protect the
      sensitive root tips by chelating the toxic Al(3+) cations in the rhizosphere to
      form non-toxic complexes. Activation of malate-permeable channels in the plasma
      membrane could be critical in regulating this malate efflux. We examined this by
      investigating Al(3+)-activated channels in protoplasts from root apices of near
      isogenic wheat differing in Al(3+) tolerance at a single locus. Using whole-cell
      patch clamp we found that Al(3+) stimulated an electrical current carried by
      anion efflux across the plasma membrane in the Al(3+)-tolerant (ET8) and Al(3+)
      sensitive (ES8) genotypes. This current occurred more frequently, had a greater
      current density, and remained active for longer in ET8 protoplasts than for ES8
      protoplasts. The Al(3+)-activated current exhibited higher permeability to
      malate(2-) than to Cl(-) (P(mal)/P(Cl) > or = 2.6) and was inhibited by anion
      channel antagonists, niflumate and diphenylamine-2-carboxylic acid. In ET8, but
      not ES8, protoplasts an outward-rectifying K(+) current was activated in the
      presence of Al(3+) when cAMP was included in the pipette solution. These findings
      provide evidence that the difference in Al(3+)-induced malate efflux between
      Al(3+)-tolerant and Al(3+)-sensitive genotypes lies in the differing capacity for
      Al(3+) to activate malate permeable channels and cation channels for sustained
      malate release.

PMID- 11244126
TI  - The high level of aluminum resistance in signalgrass is not associated with known
      mechanisms of external aluminum detoxification in root apices.
AB  - Al resistance of signalgrass (Brachiaria decumbens Stapf cv Basilisk), a widely
      sown tropical forage grass, is outstanding compared with the closely related
      ruzigrass (Brachiaria ruziziensis Germain and Evrard cv Common) and Al-resistant
      genotypes of graminaceous crops such as wheat, triticale, and maize. Secretion of
      organic acids and phosphate by root apices and alkalinization of the apical
      rhizosphere are commonly believed to be important mechanisms of Al resistance.
      However, root apices of signalgrass secreted only moderately larger quantities of
      organic acids than did those of ruzigrass, and efflux from signalgrass apices was
      three to 30 times smaller than from apices of Al-resistant genotypes of
      buckwheat, maize, and wheat (all much more sensitive to Al than signalgrass). In
      the presence, but not absence, of Al, root apices of signalgrass alkalinized the
      rhizosphere more than did those of ruzigrass. The latter was associated with a
      shortening of the alkalinizing zone in Al-intoxicated apices of ruzigrass,
      indicating that differences in alkalinizing power were a consequence, not a cause
      of, differential Al resistance. These data indicate that the main mechanism of Al
      resistance in signalgrass does not involve external detoxification of Al.
      Therefore, highly effective resistance mechanisms based on different
      physiological strategies appear to operate in this species.

PMID- 11244127
TI  - Regulation of protein degradation and protease expression by mannose in maize
      root tips. Pi sequestration by mannose may hinder the study of its signaling
      properties.
AB  - The effects of mannose (Man) and glucose (Glc) on central metabolism,
      proteolysis, and expression of the root starvation-induced protease (RSIP; F.
      James, R. Brouquisse, C. Suire, A. Pradet, P. Raymond [1996] Biochem J 320: 283
      292) were investigated in maize (Zea mays L. cv DEA) root tips. Changes in
      metabolite concentrations (sugars, ester-phosphates, adenine nucleotides, and
      amino acids) were monitored using in vivo and in vitro (13)C- and (31)P-NMR
      spectroscopy, in parallel with the changes in respiration rates, protein
      contents, proteolytic activities, and RSIP amounts. The inhibition of
      proteolysis, the decrease in proteolytic activities, and the repression of RSIP
      expression triggered by Man, at concentrations usually used to study sugar
      signaling (2 and 10 mM), were found to be related to a drop of energy metabolism,
      primarily due to a Man-induced Pi sequestration. However, when supplied at low
      concentration (2 mM) and with the adequate phosphate concentration (30 mM),
      energy metabolism was restored and Man repressed proteolysis similarly to Glc,
      when provided at the same concentration. These results indicate that Man should
      be used with caution as a Glc analog to study signalization by sugars in plants
      because possible signaling effects may be hindered by Pi sequestration.

PMID- 11244129
TI  - Expression of a gibberellin 2-oxidase gene around the shoot apex is related to
      phase transition in rice.
AB  - A major catabolic pathway for gibberellin (GA) is initiated by 2beta
      hydroxylation, a reaction catalyzed by GA 2-oxidase. We have isolated and
      characterized a cDNA, designated Oryza sativa GA 2-oxidase 1 (OsGA2ox1) from rice
      (Oryza sativa L. cv Nipponbare) that encodes a GA 2-oxidase. The encoded protein,
      produced by heterologous expression in Escherichia coli, converted GA(1), GA(4),
      GA(9), GA(20), and GA(44) to the corresponding 2beta-hydroxylated products GA(8),
      GA(34), GA(51), GA(29), and GA(98), respectively. Ectopic expression of the
      OsGA2ox1 cDNA in transgenic rice inhibited stem elongation and the development of
      reproductive organs. These transgenic plants were deficient in endogenous GA(1).
      These results indicate that OsGA2ox1 encodes a GA 2-oxidase, which is functional
      not only in vitro but also in vivo. OsGA2ox1 was expressed in shoot apex and
      roots but not in leaves and stems. In situ hybridization analysis revealed that
      OsGA2ox1 mRNA was localized in a ring at the basal region of leaf primordia and
      young leaves. This ring-shaped expression around the shoot apex was drastically
      decreased after the phase transition from vegetative to reproductive growth. It
      was absent in the floral meristem, but it was still present in the lateral
      meristem that remained in the vegetative phase. These observations suggest that
      OsGA2ox1 controls the level of bioactive GAs in the shoot apical meristem;
      therefore, reduction in its expression may contribute to the early development of
      the inflorescence meristem.

PMID- 11244128
TI  - A role for inositol 1,4,5-trisphosphate in gravitropic signaling and the
      retention of cold-perceived gravistimulation of oat shoot pulvini.
AB  - Plants sense positional changes relative to the gravity vector. To date, the
      signaling processes by which the perception of a gravistimulus is linked to the
      initiation of differential growth are poorly defined. We have investigated the
      role of inositol 1,4,5-trisphosphate (InsP(3)) in the gravitropic response of oat
      (Avena sativa) shoot pulvini. Within 15 s of gravistimulation, InsP(3) levels
      increased 3-fold over vertical controls in upper and lower pulvinus halves and
      fluctuated in both pulvinus halves over the first minutes. Between 10 and 30 min
      of gravistimulation, InsP(3) levels in the lower pulvinus half increased 3-fold
      over the upper. Changes in InsP(3) were confined to the pulvinus and were not
      detected in internodal tissue, highlighting the importance of the pulvinus for
      both graviperception and response. Inhibition of phospholipase C blocked the long
      term increase in InsP(3), and reduced gravitropic bending by 65%. Short-term
      changes in InsP(3) were unimpaired by the inhibitor. Gravitropic bending of oat
      plants is inhibited at 4 degrees C; however, the plants retain the information of
      a positional change and respond at room temperature. Both short- and long-term
      changes in InsP(3) were present at 4 degrees C. We propose a role for InsP(3) in
      the establishment of tissue polarity during the gravitropic response of oat
      pulvini. InsP(3) may be involved in the retention of cold-perceived
      gravistimulation by providing positional information in the pulvini prior to the
      redistribution of auxin.

PMID- 11244130
TI  - A TERMINAL FLOWER1-like gene from perennial ryegrass involved in floral
      transition and axillary meristem identity.
AB  - Control of flowering and the regulation of plant architecture have been
      thoroughly investigated in a number of well-studied dicot plants such as
      Arabidopsis, Antirrhinum, and tobacco. However, in many important monocot seed
      crops, molecular information on plant reproduction is still limited. To
      investigate the regulation of meristem identity and the control of floral
      transition in perennial ryegrass (Lolium perenne) we isolated a ryegrass TERMINAL
      FLOWER1-like gene, LpTFL1, and characterized it for its function in ryegrass
      flower development. Perennial ryegrass requires a cold treatment of at least 12
      weeks to induce flowering. During this period a decrease in LpTFL1 message was
      detected in the ryegrass apex. However, upon subsequent induction with elevated
      temperatures and long-day photoperiods, LpTFL1 message levels increased and
      reached a maximum when the ryegrass apex has formed visible spikelets.
      Arabidopsis plants overexpressing LpTFL1 were significantly delayed in flowering
      and exhibited dramatic changes in architecture such as extensive lateral
      branching, increased growth of all vegetative organs, and a highly increased
      trichome production. Furthermore, overexpression of LpTFL1 was able to complement
      the phenotype of the severe tfl1-14 mutant of Arabidopsis. Analysis of the LpTFL1
      promoter fused to the UidA gene in Arabidopsis revealed that the promoter is
      active in axillary meristems, but not the apical meristem. Therefore, we suggest
      that LpTFL1 is a repressor of flowering and a controller of axillary meristem
      identity in ryegrass.

PMID- 11244131
TI  - Cooperative action of SLR1 and SLR2 is required for lateral root-specific cell
      elongation in maize.
AB  - Lateral roots play an important role in water and nutrient uptake largely by
      increasing the root surface area. In an effort to characterize lateral root
      development in maize (Zea mays), we have isolated from Mutator (Mu) transposon
      stocks and characterized two nonallelic monogenic recessive mutants: slr1 and
      slr2 (short lateral roots1 and 2), which display short lateral roots as a result
      of impaired root cell elongation. The defects in both mutants act specifically
      during early postembryonic root development, affecting only the lateral roots
      emerging from the embryonic primary and seminal roots but not from the
      postembryonic nodal roots. These mutations have no major influence on the
      aboveground performance of the affected plants. The double mutant slr1; slr2
      displays a strikingly different phenotype than the single mutants. The defect in
      slr1; slr2 does not only influence lateral root specific cell elongation, but
      also leads to disarranged cellular patterns in the primary and seminal roots.
      However, the phase-specific nature of the single mutants is retained in the
      double mutant, indicating that the two loci cooperate in the wild type to
      maintain the lateral root specificity during a short time of early root
      development.

PMID- 11244132
TI  - Gold.

PMID- 11244133
TI  - Gold allergy in North America.
AB  - OBJECTIVE: To determine the prevalence of allergic reactions to gold among
      patients tested by the North American Contact Dermatitis Group (NACDG) from 1996
      to 1998. METHODS: This is a prospective analysis of patch test results from the
      12 centers that comprise the NACDG. Gold was tested as gold sodium thiosulfate
      (0.5% in petrolatum [pet]), along with 49 other screening allergens, in patients
      presenting with possible contact dermatitis. RESULTS: Of 4,101 patients tested,
      388 (9.5%) had a positive patch test result to gold. Women accounted for 62.8% of
      the subjects tested and 90.2% of patients positive to gold (P < .0001). The most
      common sites of dermatitis in gold-allergic patients were the hands (29.6%), face
      (19.3%), and eyelids (7.5%). Nickel and cobalt allergies, respectively, also were
      present in 33.5% and 18.3% of gold allergic individuals, as compared with 14.2%
      and 9.0% of the total population. Gold was the only positive reaction in 15.2% of
      the 388 patients. CONCLUSION: Gold is a more common allergen than previously
      reported and might cause facial and eyelid dermatitis. Hypersensitivity to gold
      is statistically linked to female gender and to allergic reactions to nickel and
      cobalt.

PMID- 11244134
TI  - Dermal exposure to cinnamaldehyde alters lymphocyte subpopulations, number of
      interferon-gamma-producing cells, and expression of B7 costimulatory molecules
      and cytokine messenger RNAs in auricular lymph nodes of B6C3F1 mice.
AB  - BACKGROUND: Although the Murine Local Lymph Node Assay (LLNA) is efficient in
      identifying chemicals with sensitizing potential, there is increasing need for
      alternative end points. Cinnamaldehyde (CIN) was chosen for evaluation based on
      its moderate potency and extensive use in fragrance materials. OBJECTIVES: The
      purpose of the present studies is to incorporate some alternative end points,
      such as phenotypic analysis and cytokine production, into a modified
      LLNA/irritancy assay (IA) to evaluate the sensitization of female B6C3F1 mice to
      CIN. METHODS: Several nontraditional end points, including the analysis of
      lymphocyte subpopulations, B7 costimulatory molecule and cytokine messenger RNA
      (mRNA) expression, and intracellular interferon-gamma (IFN-gamma) levels, were
      incorporated into a modified murine local lymph node (LLNA)/irritancy assay (IA)
      to evaluate the sensitization of female B6C3F1 mice to cinnamaldehyde (CIN).
      RESULTS: The alternate end points used in these studies support the
      classification of CIN as a moderately potent sensitizer. Dermal treatment with
      CIN resulted in an increase in the percentage of B cells in the auricular lymph
      nodes (ALNs) and expression of the costimulatory molecule, B7-2, on B cells.
      Lymph node cells also showed increased transforming growth factor-beta1,
      migration-inhibition factor, and mild increases in IFN-gamma and interleukin-2
      cytokine mRNA expression. Although the increase in IFN-gamma mRNA expression did
      not translate into increased intracellular IFN-gamma levels, the absolute number
      of T cells producing IFN-gamma in the ALNs increased. Conversely, the MEST did
      not classify CIN as a contact allergen. CONCLUSION: The nontraditional end points
      used in the LLNA/IA were not as sensitive as the traditional radioisotope method
      used to assess cell proliferation. However, they may help identify compounds
      inappropriately classified as sensitizers or nonsensitizers by the LLNA and MEST.

PMID- 11244136
TI  - Effect of patch type on the cumulative irritation potential of 4 test materials.
AB  - BACKGROUND: Many different patch systems are available for predicting contact
      dermatitis. It is important to determine the ideal patch to meet the objective of
      the testing method. OBJECTIVE: The 21-day cumulative irritation test is well
      accepted for predicting irritation after repeated exposures. The patch type must
      allow separation of materials to predict irritation potential in the marketplace.
      Three patch systems were compared to determine which best provides this
      separation and prediction. METHODS: Four test materials were evaluated using 3
      patch systems in a 21-day cumulative irritation test. Tested were water, 0.06%
      sodium lauryl sulfate (SLS), and 2 underarm products (UAP), one having lower and
      one having higher irritation potential. The patch types were; Webril pad and 8-mm
      and 12-mm Finn Chambers. RESULTS: Both the 12-mm Finn Chamber and Webril pad
      showed the ability to differentiate the higher irritating UAP and the 0.06% SLS
      from the lower irritation UAP product and water. The 8-mm Finn chamber was less
      discriminating, showing the 0.06% SLS to be the same as water and the lower
      irritating UAP. CONCLUSION: The Webril pad and the 12-mm Finn Chamber are better
      at discriminating irritation potential than is the 8-mm Finn Chamber. The 12-mm
      Finn Chamber might also allow discrimination with a lower degree of irritation.

PMID- 11244135
TI  - Patch test sensitization to Compositae mix, sesquiterpene-lactone mix, Compositae
      extracts, laurel leaf, Chlorophorin, Mansonone A, and dimethoxydalbergione.
AB  - BACKGROUND: Compositae mix and sesquiterpene-lactone (SL) mix are important patch
      test substances to show allergic contact dermatitis from various Compositae
      plants. OBJECTIVES: The aims of this study are to calculate the sensitization
      rates to Compositae mix and SL mix in an occupational dermatology clinic and to
      describe cases of active sensitization caused by patch testing with Compositae
      mix and SL mix. METHODS: Conventional patch testing was performed. SL mix (0.1%)
      and Compositae mix (6% in petrolatum) were tested in a modified European standard
      series and a plant allergen series. Testing with other appropriate patch test
      series was also performed. RESULTS: SL mix provoked 8 allergic patch test
      reactions (0.7%) in 1,076 patients, whereas Compositae mix was positive in 15 of
      346 patients (4.2%). Three patients were actively sensitized to Compositae mix
      and 1 patient to SL mix. One patient was also sensitized to other plant allergens
      in a series of allergenic plant chemicals, namely to Mansonone A, an ortho
      quinone; (R)-3,4-dimethoxydalbergione, a quinone; and Chlorophorin, a hydroxy
      stilbene. Allergic patch test reactions to laurel leaf were caused by cross
      sensitization to SLs. CONCLUSION: Compositae mix seems to be a more important
      patch test substance than SL mix to detect allergic contact dermatitis to
      Compositae plants, but patch testing may sensitize. The concentration of the
      individual components of the Compositae mix should be adjusted so that the mix
      detects allergic patients but does not sensitize.

PMID- 11244137
TI  - Pitfalls of irritant patch testing using different test chamber sizes.
AB  - BACKGROUND: Test chambers for irritant patch testing are usually larger than
      those used in allergic patch testing. In general, larger areas show stronger skin
      reactions than smaller areas. OBJECTIVE: This study investigated whether this
      difference is of practical relevance, when a model irritant is applied in small
      and large Finn chambers and evaluated by measurement of transepidermal water loss
      (TEWL). METHODS: Patch testing was performed with 2 concentrations of sodium
      lauryl sulfate (SLS) (0.25% and 0.5%) on forearms of healthy volunteers. Large
      (inner diameter, 12 mm) and small (inner diameter, 8 mm) chambers were used.
      RESULTS: A variance analysis (3 factors, 2-tailed) showed that the test outcome,
      as assessed by TEWL, was strongly dependent on SLS test concentration and test
      chamber size. The larger chambers gave approximately 30% to 50% higher values
      than the smaller. CONCLUSIONS: This may be explained by the fact that with the
      small chambers, the adjacent small area of nontreated skin was also assessed by
      the evaporimeter, biasing the results. A formula estimating TEWL value of the
      large chamber from values of the small chambers has been proposed.

PMID- 11244138
TI  - Allergic contact dermatitis from a bleaching cream.

PMID- 11244139
TI  - Allergic contact dermatitis from a pyridine derivative in polyvinyl chloride
      leather.
AB  - Antimicrobial coating of household products has gained wide acceptance in Japan
      in the past several years. Pyridine derivatives, used as antifungal or
      antibacterial agents in many common products, are known to cause contact
      dermatitis. We present a case of severe contact dermatitis caused by a pyridine
      derivative used as an antifungal agent in the polyvinyl chloride (PVC) leather of
      a chair. An open patch test was performed with each ingredient of the PVC
      leather. Other products were previously eliminated from consideration based on a
      series of negative patch tests. The PVC leather obtained from the patient's chair
      gave a ++ reaction with evident blistering, according to the International
      Contact Dermatitis Research Group standard. Fifteen ingredients of the PVC
      leather were open patch tested; a positive reaction was found with 2,3,5,6
      tetrachloro-4 (methylsulphonyl) pyridine (1% in petrolatum). Clinicians should be
      aware that antifungal or antibacterial agents may be increasingly incorporated
      into common household products and should be suspected in cases of contact
      dermatitis.

PMID- 11244140
TI  - Eyelid allergic contact dermatitis to black iron oxide.
AB  - Eye cosmetics are a common cause of eyelid dermatitis. These products contain
      pigments, fragrances, resins, preservatives and vehicles. Mascara might cause
      either irritant or allergic contact dermatitis (ACD) of the eyelids. We present
      the case of a 44-year-old woman with a 10-month history of periorbital and eyelid
      dermatitis. Epicutaneous patch testing using the TRUE Test, cosmetic series,
      steroid series, and her personal products yielded a strong reaction to her
      mascara. Subsequent patch testing to the mascara components provided by the
      manufacturer revealed a severe reaction only to 5% black iron oxide. This black
      iron oxide was further tested in 10 normal controls with no reactions produced.
      There is only one previous report of eyelid ACD secondary to iron oxide that
      represents a rare cause of eyelid ACD.

PMID- 11244141
TI  - The Botanical Dermatology Database (http://BoDD.cf.ac.uk): an electronic
      reincarnation of Mitchell and Rook's Botanical Dermatology.
AB  - An account is provided of the history and planned development of BoDD: Botanical
      Dermatology Database, a major Internet resource.

PMID- 11244142
TI  - Overlapping meetings of the Experimental Contact Dermatitis Research Group and
      the American Contact Dermatitis Society.

PMID- 11244143
TI  - Familial relationship between mood disorders and alcoholism.
AB  - Clinical and epidemiological studies have consistently revealed an association
      between alcohol use disorders and both bipolar and nonbipolar mood disorders.
      However, the evidence regarding the nature of these associations is unclear. The
      familial patterns of alcohol and affective disorders were examined using data
      from a controlled family study of probands with alcohol and anxiety disorders who
      were sampled from treatment settings and the community. The substantial degree of
      comorbidity between mood and anxiety disorders among probands allowed for the
      examination of comorbidity and familial aggregation of alcohol and mood
      disorders. The major findings are that (1) alcoholism was associated with bipolar
      and nonbipolar mood disorders in the relatives; (2) there was a strong degree of
      familial aggregation of alcohol dependence and both types of mood disorders were
      observed; and (3) there was no evidence of cross-aggregation (i.e., increase in
      mood disorders among probands with alcohol dependence, and vice versa) between
      alcoholism and mood disorders. The independent familial aggregation of bipolar
      disorder and alcoholism and the finding that the onset of bipolar disorder tended
      to precede that of alcoholism are compatible with a self-medication hypothesis as
      the explanation for the frequent co-occurrence of these disorders. In contrast,
      the independent familial aggregation and the tendency of an earlier onset of
      alcoholism than that of nonbipolar depression suggest that unipolar mood
      disorders are frequently secondary to alcoholism.

PMID- 11244144
TI  - Family functioning and suicidality in depressed adults.
AB  - This study examined the association between suicidality, family factors, and
      clinical and diagnostic variables in depressed adult inpatients. The subjects
      were 121 depressed adult inpatients living with a family member or significant
      other. Demographic, clinical, and diagnostic information about the patient, and
      subjective and observer ratings of family functioning were obtained. Trained
      interviewers rated families of suicidal depressed patients as more dysfunctional
      than families of patients with no history of attempted suicide. In a logistic
      regression model, earlier age of depression onset, number of psychiatric
      hospitalizations, and objectively rated poorer family communication were
      associated with a history of a prior suicide attempt. Also, modest evidence
      suggested that patients with a prior suicide attempt perceived their families as
      more dysfunctional than did their respective family members. Variations in family
      functioning are associated with different degrees of suicidality. However,
      prospective longitudinal designs would elucidate the causal relation between
      family dysfunction and suicidal behavior.

PMID- 11244145
TI  - Genetic studies of seasonal affective disorder and seasonality.
AB  - Genetic studies of seasonal affective disorder (SAD) and seasonality have
      received considerable attention over the past several years. Studies of the
      prevalence of SAD and nonseasonal mood disorders among relatives of patients with
      SAD suggested a familial contribution to the development of SAD. Two twin studies
      demonstrated a substantial role of genetic variation in seasonality. Two genetic
      variants related to serotonergic transmission, the 5-HTTLPR and the 5-HT(2A)
      1438G/A gene promoter polymorphisms, have been found to be associated with SAD. 5
      HTTLPR is also associated with seasonality in SAD patients and in the general
      population. It is not clear whether SAD is inherited as a distinct entity or
      whether seasonality and depression are separate heritable traits that happen to
      coincide in certain individuals. Vulnerability to SAD and disease pathology may
      be influenced by many genes, perhaps on several chromosomes.

PMID- 11244146
TI  - Gender differences in risk factors for trauma exposure and post-traumatic stress
      disorder among inner-city drug abusers in and out of treatment.
AB  - Over the past two decades there has been a growing awareness of the comorbidity
      between post-traumatic stress disorder (PTSD) and substance use disorders in the
      general population. The purpose of these analyses was to examine, in a population
      of drug users, the role of gender in (1) predicting the nature of the traumatic
      event and PTSD symptoms, (2) patterns of substance use disorders in relation to
      trauma exposure and PTSD symptoms, (3) comorbidity of other psychiatric disorders
      with trauma exposure and PTSD, and (4) the temporal association of substance use
      disorder, exposure to trauma, and PTSD. Drug abusers (n = 464) were interviewed
      using the Diagnostic Interview Schedule for DSM-III-R (DIS) and the Composite
      International Diagnostic Interview-Substance Abuse Module (CIDI-SAM). Although
      more women than men met criteria for DSM-III-R PTSD, there were no gender
      differences on endorsement for a traumatic event. Adult antisocial behavior,
      affective disorder, schizophrenia, other anxiety disorder and polysubstance use
      predicted exposure to an event, whereas, only schizophrenia and other anxiety
      disorder predicted PTSD. In men, drug use preceded the exposure to an event,
      while in women, the onset age for both drug use and exposure to an event were
      nearly identical. This work suggests implications for gender-based education and
      prevention interventions.

PMID- 11244147
TI  - Psychosocial correlates of suicidal intent among patients with schizophrenia.
AB  - Suicidal intent is common among patients with schizophrenia, resulting in extreme
      personal distress, increased hospitalizations and healthcare expenditures, and
      early mortality. However, the psychosocial correlates of current suicidality
      among schizophrenic patients are not fully understood. This study attempted to
      identify psychosocial correlates of current suicidal intent in a sample of 267
      patients with schizophrenia. Multiple regression analyses were used to assess the
      relationship between suicidality and current symptomatology, psychosocial
      problems, global functioning, and demographic characteristics. Results showed
      that depressive symptomatology as a single variable accounted for approximately
      50% of the variance in ratings of suicidal intent. In addition, female gender,
      younger age, recent traumatic stress, and less severe psychotic symptoms each
      significantly predicted current suicidality independent of depressive symptoms.
      The combination of depression among younger female schizophrenic patients whose
      psychotic symptoms have abated and who are experiencing current traumatic stress
      may indicate extreme suicidal intent.

PMID- 11244148
TI  - Medication use and major depressive syndrome in a community population.
AB  - A variety of medications have been reported to cause depression as a side effect.
      This study evaluated cross-sectional associations between a variety of
      medications and a syndrome resembling major depression. A sample of 2,542
      subjects were selected using the Mitofsky-Waksberg random digit dialing (RDD)
      procedure. Major depression was evaluated using a short form version of the
      Composite International Diagnostic Interview (CIDI). Current medication use was
      recorded during the same telephone interview. Statistical methods accounting for
      clustering and unequal selection probabilities were employed. Most medications
      were not associated with major depression: these included beta-blockers,
      angiotensin-converting enzyme (ACE) inhibitors, lipid-lowering agents, digoxin,
      and diuretics. Calcium channel blockers were significantly associated with major
      depression, but only in a subset of young subjects, and these tended to be
      seriously ill individuals taking multiple medications. Opiate analgesics were
      associated with major depression, but only in male subjects. Corticosteroids were
      significantly associated with major depression in a logistic regression model
      that adjusted for age and gender. The cross-sectional nature of this study
      precludes causal inference about the observed associations. With the exception of
      the association of major depression with corticosteroid use, convincing
      associations with other medications were not observed. It is possible that
      medication-induced depressive episodes lead to changes in exposure status (such
      as discontinuation of the offending medications) such that the associations are
      not apparent in cross-sectional data. If this interpretation is correct, these
      data suggest that the problem of medication-induced depression is being managed
      effectively at the clinical level and is not a substantial public health problem.

PMID- 11244149
TI  - Psychoeducation for the families of patients with eating disorders and changes in
      expressed emotion: A preliminary study.
AB  - Psychosocial variables such as expressed emotion (EE) have prognostic
      significance, and family psychoeducation has been developed to aid in the
      treatment of various psychiatric disorders. This study reports relationships
      among EE, family factors, and symptoms observed while conducting multifamily
      psychoeducation for eating disorders. Group sessions were held once a month for
      the relatives of patients with DSM-IV eating disorders, and the group met for
      five sessions that included both education and problem-solving. Thirty-seven
      relatives volunteered to participate in our program, and of these, 28 completed
      the program. EE (as measured by the Five-Minute Speech Sample [FMSS]), family
      function (as measured by the Family Adaptability and Cohesion Evaluation Scales
      [FACES]), the family's mental state (as measured by the Profile of Mood States
      [POMS]), and patient's symptoms (as measured by the Eating Disorder Evaluation
      Scales [EDES] and Global Assessment of Functioning [GAF] on clinician
      evaluations, and by the Anorexic Behavior Observation Scale [ABOS] assessment of
      the family) were administered at both the first and final sessions. The rates of
      high-EE relatives tended to decrease (especially high emotional overinvolvement
      [EOI]), and families' assessment of symptoms was also significantly improved.
      Twice-repeated multivariate analysis of variance (MANCOVA) showed that EOI, ABOS,
      and POMS scores were changed significantly during the sessions. Psychoeducation
      for the family members of patients with eating disorders might help lower
      distress and encourage positive interactions within the family. EE is an
      important measure in evaluations of psychoeducation. However, a randomized,
      controlled trial is needed to clarify the efficacy of this treatment.

PMID- 11244150
TI  - Major depressive episodes with hypomanic symptoms are common among depressed
      outpatients.
AB  - Depressive mixed states (major depressive episodes [MDE] with some hypomanic
      symptoms) are not classified in DSM-IV. The aim of the present study was to
      determine the prevalence of depressive mixed states in depressed outpatients, and
      to compare bipolar II with unipolar depressive mixed states. Seventy consecutive
      bipolar II and unipolar depressed outpatients were interviewed using the DSM-IV
      Structured Clinical Interview (SCID). At least one hypomanic symptom was present
      in 90% of patients, and three or more in 28.5%. Symptoms of depressive mixed
      states included irritable mood, distractibility, racing thoughts, and increased
      talking. Bipolar II subjects had more concurrent hypomanic symptoms (three or
      more in 48.7% v 3.2%, P = 0.000). Depressive mixed states with three or more
      hypomanic symptoms correctly classified 70.0% of bipolar II subjects. These
      findings have important treatment implications, as antidepressants may worsen the
      symptoms of depressive mixed states, and mood stabilizers can be useful.

PMID- 11244152
TI  - Gender differences in psychosocial risk factors for psychological distress among
      immigrants.
AB  - The reasons for a greater prevalence of psychological distress among women than
      men remain unknown. We sought to test two hypotheses that gender operates either
      as (1) a moderator or (2) a mediator between psychosocial risk factors and
      experienced distress. A cross-sectional community survey of 1,062 adult Russian
      born Jewish immigrants to Israel was conducted. The Demographic Psychosocial
      Inventory (DPSI) and the Talbieh Brief Distress Inventory (TBDI) were used to
      measure the parameters of interest. Univariate and multivariate analyses were
      used to test the moderation versus mediational hypotheses of gender in the stress
      distress relationship. The aggregate levels of psychological distress and
      depression, anxiety, and obsessive symptoms were significantly higher for women
      than for men. Five sources of distress were more likely to be reported by women:
      family problems, inappropriate climatic conditions, anxiety about the future,
      poor health status, and uncertainty in the present life situation. Men scored
      higher on three stress-protective factors: the number of reasons for immigration,
      commitment to the host country, and job adequacy. Results of multiple regression
      and multivariate analysis of variance (MANOVA) supported the mediation hypothesis
      that gender differences in psychological distress stem from women's greater
      exposure to specific psychosocial stressors. Our findings demonstrate the
      validity of gender as an important mediating mechanism underlying the
      differential perception of risk factors for the development of psychological
      distress.

PMID- 11244151
TI  - Treatment histories of borderline inpatients.
AB  - In this study, we describe the types and amounts of psychiatric treatment
      received by a well-defined sample of borderline personality disorder (BPD)
      inpatients, and compare these parameters with those of a group of carefully
      diagnosed personality-disordered controls. Finally, we assess the risk factors
      associated with a history of intensive, high-cost treatment, which we defined as
      having had two or more prior psychiatric hospitalizations. The treatment
      histories of 290 borderline inpatients and 72 axis II controls were assessed
      using a reliable semistructured interview. All nine forms of treatment studied
      except electroconvulsive therapy (ECT) were common among borderline patients (36%
      to 96%). In addition, a significantly higher percentage of borderline patients
      than axis II controls reported a history of individual and group therapy, day and
      residential treatment, psychiatric hospitalization, participating in self-help
      groups, and taking standing medications. They were also significantly younger
      when they first entered individual therapy and began to take standing
      medications. In addition, borderline patients spent more time than axis II
      controls in individual therapy and psychiatric hospitals, and were on standing
      medications for a significantly longer period of time. They also reported a
      significantly higher number of psychiatric hospitalizations, lifetime number of
      standing medications, and number of psychotropic medications taken at the same
      time. In addition, we found a highly significant multivariate predictive model
      for multiple prior hospitalizations. The six significant predictors were age 26
      or older, a history of quasi psychotic thought, lifetime number of self
      mutilative efforts and suicide attempts, a childhood history of reported sexual
      abuse, and an adult history of being physically and/or sexually assaulted. Taken
      together, these results confirm clinical impressions concerning the high rates of
      mental health services used by borderline patients. They also suggest that
      particularly high rates of costly inpatient treatment are associated with a
      complex admixture of older age, BPD symptoms in the cognitive and impulse realms,
      and traumatic life experiences occurring in both childhood and adulthood.

PMID- 11244153
TI  - Reliability and validity of the Turkish version of the Hamilton Depression Rating
      Scale.
AB  - The aim of the study was to examine the reliability and validity of the Turkish
      version of the Hamilton Depression Rating Scale (HDRS). Ninety-four patients with
      major depression/depressive mood disorders and 40 healthy controls participated
      in the study. The severity of depression was assessed with the HDRS, Beck
      Depression Inventory (BDI), and Clinical Global Impression score (CGI). The test
      retest reliability coefficient of the HDRS was based on a 5-day interval was.85,
      with a Cronbach alpha coefficient of.75 and a split-half reliability coefficient
      of.76. Interrater reliability coefficients based on the independent ratings of
      four assessors were between.87 and.98. The correlation between the HDRS and BDI
      scores was.48, and between the HDRS and CGI it was.56. Principal Components
      Analysis yielded six factors. The correlation (-.13) between the control and
      patient groups indicates that the HDRS assesses depression very well.

PMID- 11244154
TI  - Improving screening for mental disorders in the primary care setting by combining
      the GHQ-12 and SCL-90-R subscales.
AB  - Most of patients with mental disorders are cared for in the primary care sector,
      rather than in the mental health sector. Self-report questionnaires can be used
      as screening instruments to identify mental disorders in primary care. The 12
      item General Health Questionnaire (GHQ-12) is a widely used screening
      questionnaire for common mental disorders. Unfortunately, the GHQ-12 generates
      many false presumptive positives and forces the employer to expend resources on
      confirmatory testing. Therefore, the aim of the present report was to investigate
      a two-stage questionnaire screening design in a primary care setting. The GHQ-12
      was used as an initial screening test followed by the Symptom Checklist (SCL-90
      R). A randomly selected sample of adult outpatients (N = 408) from 18 primary
      care offices was screened using the two questionnaires. A structured diagnostic
      interview and an impairment rating were used as standards. Subjects were
      classified into true-positives and false-positives based on their GHQ-12 score
      and the clinical interview. Logistic regression and receiver operating
      characteristic analysis were performed to determine whether the SCL-90-R
      increased accuracy in screening for mental disorders by discriminating between
      true-positive and false-positive cases. The SCL-90-R subscales Depression,
      Obsessive-Compulsive, and Somatization were identified as factors associated with
      the GHQ-12 classification. Therefore, a significant improvement in screening
      performance of the GHQ-12 is obtained by combination of the test results. The
      approach may reduce artifact due to high scoring tendencies not associated with
      psychological disorder.

PMID- 11244155
TI  - Immune activation is required for the induction of liver allograft tolerance:
      implications for immunosuppressive therapy.
AB  - Liver transplants in many animal models are unusual because often they are not
      rejected even when transplanted across complete major histocompatibility complex
      barriers without immunosuppression. Their paradoxical behavior is even more
      obvious when the immune mechanism of acceptance is examined. Instead of
      acceptance resulting from a lack of immune response to the graft, the opposite
      occurs, and there is an unusual extensive increase in immune activation in
      acceptance compared with rejection. This abnormal extensive immune activation is
      driven by donor leukocytes transferred with the liver and results in death of the
      recipient cells that would normally reject the transplant. Some forms of
      immunosuppression inhibit this activation-associated liver transplant tolerance.
      The significance of these findings and possible means to design future treatment
      protocols for clinical transplantation that optimize management of liver
      transplant recipients are discussed.

PMID- 11244156
TI  - Preliminary results of a liver allocation plan using a continuous medical
      severity score that de-emphasizes waiting time.
AB  - Liver allocation remains problematic because current policy prioritizes status 2B
      or 3 patients by waiting time rather than medical urgency. On February 21, 2000,
      we implemented a variance to the United Network for Organ Sharing liver
      allocation policy that redefined status 2A by much more rigid, definable criteria
      and prioritized status 2B patients by using a continuous medical urgency score
      based on the Child-Turcotte-Pugh score and other medical conditions. In this
      system, waiting time is used only to differentiate status 2B candidates with
      equal medical urgency scores. Comparing the 6-month period (period 1; n = 67)
      before implementation of this system to the 6-month period after implementation
      (period 2; n = 75), there was a significant reduction in the number of
      transplantations performed for patients listed as status 2A (46.3% to 14.7%; P
      =.002) and an increase in the number of patients listed as status 2B who received
      transplants (44.8% to 70.7%; P =.10). Most dramatically, there was a 37.1%
      reduction in overall deaths on the waiting list from 94 deaths in period 1 to 62
      deaths in period 2 (P =.005), with the most significant reduction for patients
      removed from this list at status 2B (52 v 18 patients; P =.04). There were 3
      postoperative deaths in each period, with only 1 graft lost in period 2. Status
      2B patients with the greatest degree of medical urgency received transplants
      without multiple peer reviews requesting elevation to 2A status. We conclude that
      a continuous medical urgency score system allocates donor livers much more fairly
      to those in medical need and reduces waiting list mortality without sacrificing
      efficacy.

PMID- 11244157
TI  - Proposing change in organ allocation.

PMID- 11244158
TI  - Treatment of progressive hepatitis C recurrence after liver transplantation with
      combination interferon plus ribavirin.
AB  - Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT)
      is common, although the majority of cases are mild. A subset of transplant
      recipients develops progressive allograft injury, including cirrhosis and
      allograft failure. Minimal data are available on the safety and efficacy of
      antiviral treatment in this group of patients. The aim of this study is to review
      our experience in the treatment of moderate to severe HCV recurrence with
      combination interferon-alpha2b and ribavirin (IFN/RIB). Between October 1993 and
      October 1999, a total of 197 patients underwent OLT for HCV-related liver
      failure. This study describes 12 transplant recipients with moderate to severe
      recurrence treated with IFN/RIB. All patients met at least 1 of the following
      inclusion criteria: (1) moderate to severe inflammation (grade III to IV) on
      allograft biopsy, (2) bridging fibrosis on allograft biopsy, or (3) severe
      cholestasis attributable solely to HCV recurrence. Two patients had undergone re
      OLT for allograft cirrhosis secondary to HCV recurrence and now had evidence of
      progressive HCV in their second allografts. Appropriate dose reductions of both
      IFN and RIB, as well as initiation of granulocyte colony-stimulating factor (G
      CSF), for marked leukopenia were recorded. IFN/RIB therapy was started 60 to 647
      days post-OLT, and duration of therapy ranged from 39 to 515 days. Seven patients
      were administered G-CSF to successfully treat leukopenia. Six of the 12 patients
      (50%) became HCV RNA negative by polymerase chain reaction. One of these 6
      patients (no. 1) was HCV RNA negative at 6 months but chose to discontinue
      therapy because of intolerable side effects, experienced a relapse, and was HCV
      RNA positive at 12 months. Two of the remaining 5 patients were HCV RNA negative
      at 2 and 9 months off therapy. For the entire group, there was a statistically
      significant decrease in serum biochemical indices assessed at initiation of
      therapy and 1, 3, and 6 months into therapy. Most patients required dose
      reductions of both IFN and RIB. Five patients died; 3 patients died of liver
      related complications that included severe intrahepatic biliary cholestasis,
      severe HCV recurrence, and chronic rejection with profound cholestasis. In the
      subset of HCV-positive liver transplant recipients with moderate to severe
      recurrence, combination IFN/RIB therapy resulted in complete virological response
      (serum RNA negative) in 6 of 12 patients ( approximately 50%). However, only 1 of
      12 patients (8.3%) had sustained virological clearance after cessation of IFN/RIB
      therapy. Dose reductions of both IFN and RIB were required in most patients. The
      use of G-CSF (sometimes preemptively) allowed correction of leukopenia and full
      dose antiviral therapy. Multicenter trials using combination therapy to identify
      factors predictive of response are needed in the subset of patients with
      progressive allograft injury.

PMID- 11244159
TI  - Employment and alcohol use after liver transplantation for alcoholic and
      nonalcoholic liver disease: a systematic review.
AB  - The purpose of the study is to evaluate patterns of employment and alcohol use
      among liver transplant recipients with alcoholic (ALD) and nonalcoholic liver
      disease (non-ALD). MEDLINE, EMBASE, and bibliographic searches identified 5,505
      potentially relevant articles published between January 1966 and October 1998.
      Eighty-two studies reporting data on 5,020 transplant recipients met our
      inclusion criteria. Pre-orthotopic liver transplantation (OLT), 29% of transplant
      recipients with ALD and 59% of those with non-ALD worked versus 33% and 80% at 3
      years for transplant recipients with ALD and non-ALD, respectively (P <.00001 for
      each interval). We found no difference in the proportion of transplant recipients
      with ALD and non-ALD reporting early alcohol use post-OLT: 4% versus 5% at 6
      months and 17% versus 16% at 12 months. However, among post-OLT drinkers,
      transplant recipients with non-ALD were more likely to drink moderately and those
      with ALD to drink excessively. At 7 years post-OLT, 32% of the patients with ALD
      reported using alcohol. The odds ratio for alcohol use among patients who
      maintained abstinence for fewer than 6 months pre-OLT versus those who maintained
      abstinence for greater than 6 months was 7.8 (95% confidence interval, 4.0 to
      15.3). Before OLT and at long-term follow-up, substantially more transplant
      recipients with non-ALD than ALD were employed. The proportions of transplant
      recipients with ALD and non-ALD reporting alcohol use did not differ, although
      those with ALD tended to consume greater quantities.

PMID- 11244160
TI  - Alcohol relapse and functional outcome after liver transplantation for alcoholic
      liver disease.

PMID- 11244161
TI  - Fitness testing of pediatric liver transplant recipients.
AB  - Liver transplantation is accepted as the standard management for end-stage liver
      disease in children. Pediatric heart and heart-lung transplant recipients have
      shown significantly diminished exercise capacities compared with age-matched,
      able-bodied, control subjects. The primary aim of this study is to compare the
      fitness levels of a group of pediatric liver transplant (LT) recipients (LT
      group, 20 boys, 9 girls; age, 8.9 +/- 4.8 years; 56 +/- 35 months
      posttransplantation) with a group of able-bodied control subjects (22 boys, 12
      girls; age, 8.4 +/- 3.8 years). The secondary aim is to compare the performance
      of the LT group against the Fitnessgram criterion standards. We assessed muscular
      endurance by means of a partial curl-up, flexibility by means of the back-saver
      sit and reach, and cardiorespiratory fitness by means of the progressive aerobic
      cardiovascular endurance run (PACER). The only significant (P <.05) difference
      between the 2 groups was the number of shuttles run in the PACER (control, 16.8
      +/- 9.8 v LT, 11.5 +/- 8.4 shuttles). Other differences between the 2 groups were
      not significant. With regard to satisfying the Fitnessgram criterion standards,
      only 35% of the LT group achieved the standards for the partial curl-up, 88% of
      the LT group achieved the criterion standards for flexibility, and 0% achieved
      the standards for the PACER. These results indicate that the LT group has
      diminished exercise capacity. The origins of exercise limitations deserve further
      investigation.

PMID- 11244162
TI  - Physical activity and health-related quality of life in liver transplant
      recipients.
AB  - The US Surgeon General's Report on Physical Activity and Health recommends that
      people of all ages engage in regular physical activity, and that significant
      health benefits can be obtained through a moderate amount of physical activity.
      Physical activity appears to improve health-related quality of life (HRQOL) by
      enhancing physical functioning in persons compromised by poor health. The Medical
      Outcomes Study Short Form-36 (SF-36) Health Status Questionnaire was sent to all
      patients who were 5 years or more post-liver transplantation at the University of
      California at San Francisco. Additional questions related to coexisting medical
      conditions and participation in regular physical activity were included. SF-36
      scale scores were compared between active and inactive patients. Regression
      analysis was also performed to determine the contributions of coexisting medical
      conditions and physical activity to the physical scales of the SF-36
      questionnaire. Patients who participated in regular physical activity had
      significantly higher scores on all physical scales and the physical component
      scale (PCS). The regression model, which included age, sex, time
      posttransplantation, retransplantation, recurrence of hepatitis C, number of
      comorbid conditions, and physical activity participation showed that both the
      number of comorbid conditions and participation in physical activity were
      significant independent contributors to the physical functioning scale and PCS.
      This study indicates that physical activity is related to HRQOL after liver
      transplantation independent of other coexisting medical conditions.

PMID- 11244163
TI  - Use of daclizumab as initial immunosuppression in liver transplant recipients
      with impaired renal function.
AB  - The addition of daclizumab (a human immunoglobulin G1 monoclonal antibody that
      blocks interleukin-2 receptors on T lymphocytes) to mycophenolate mofetil (MMF)
      and steroids is a new option for initial immunosuppression in patients undergoing
      liver transplantation (LT) with impaired renal function. We evaluated the
      efficacy and safety of daclizumab in preventing rejection in 25 patients with
      impaired kidney function undergoing LT. Patients with serum creatinine (Cr)
      levels greater than 2 mg/dL immediately before LT were administered initial
      immunosuppression with daclizumab, 1 mg/kg, in addition to MMF, 2 g/d, and
      methylprednisolone. Tacrolimus was added after kidney function improved (when Cr
      levels improved by >25% of initial value). Daclizumab-treated patients were
      compared retrospectively with 2 other groups of patients who underwent LT with
      kidney impairment (Cr > 2 mg/dL): 56 patients were administered OKT3 induction,
      and 48 patients were administered low-dose tacrolimus. The incidence of rejection
      and infection (bacterial, fungal, and viral), need for preoperative and
      postoperative dialysis, Cr level immediately post-LT and at 3 months, and graft
      and patient survival were analyzed. There was no difference among the groups in 3
      month Cr levels or the incidence of rejection or fungal or viral infection. The
      daclizumab group had fewer bacterial infections (n = 13) than the tacrolimus
      group (n = 28) and significantly fewer than the OKT3 group (n = 58; P =.006).
      Only 1 patient (4%) in the daclizumab group required dialysis post-LT versus 13
      patients in each of the other groups (OKT3, 23.21%; P <.05; tacrolimus, 27%). In
      the daclizumab group, 2-year patient and graft survival rates were statistically
      significant compared with the low-dose tacrolimus group (89% and 81% v 73% and
      69%, respectively; P =.06). There were no side effects related to daclizumab use,
      and all patients tolerated the drug well. In patients with impaired renal
      function before LT, daclizumab-based initial immunosuppression can be used safely
      to reduce the risk for infection and need for dialysis post-LT, with improved
      long-term graft and patient survival.

PMID- 11244164
TI  - Liver transplantation in cirrhotic patients with diabetes mellitus: midterm
      results, survival, and adverse events.
AB  - Liver cirrhosis is frequently associated with diabetes mellitus (DM), and this
      metabolic complication is also frequent after orthotopic liver transplantation
      (OLT). The aim of our study is to investigate which factors are associated with
      DM before and after OLT and their impact on post-OLT evolution. We evaluated the
      prevalence of DM among 115 liver transplant candidates with cirrhosis and
      assessed their evolution after OLT (median follow-up, 41 months). Sixteen
      candidates had DM requiring pharmacological therapy (group A), 45 candidates had
      DM controlled with diet (group B), and 54 candidates did not have DM (group C).
      One-year and 3-year actuarial survival rates were 100% and 100% for group A, 91%
      and 85% for group B, and 77% and 74% for group C, respectively (P <.03). Post-OLT
      DM was more frequent in group A. The incidence of other metabolic complications,
      major infections, rejection, and arterial hypertension; the need for
      hospitalization; and renal and graft function of patients in groups A, B, and C
      were similar. The only risk factor for DM 1 year after OLT on multivariate
      analysis was pre-OLT DM requiring pharmacological treatment. The incidence of
      complications, need for hospitalization, and renal and graft function 1 year
      after OLT for patients with post-OLT DM were similar to those of patients without
      post-OLT DM. In conclusion, patients with cirrhosis who have DM have a greater
      risk for post-OLT DM, but their midterm survival is not worse than the survival
      of those without DM.

PMID- 11244165
TI  - Liver transplantation in cirrhotic patients with diabetes mellitus.

PMID- 11244166
TI  - Liver transplantation for polycystic liver disease.
AB  - Polycystic liver disease (PLD) may provoke massive hepatomegaly and severe
      physical and social handicaps. Data on orthotopic liver transplantation (OLT) for
      PLD are rare and conflicting. Conservative surgery (resection or fenestration) is
      indicated for large single cysts, but its value for small diffuse cysts is
      questionable. In addition, conservative surgery is not devoid of morbidity and
      mortality. OLT offers the prospect of a fully curative treatment, but controversy
      remains because those patients usually have preserved liver function. Thus, we
      reviewed our experience with OLT for PLD. Sixteen adult women underwent OLT for
      small diffuse PLD between 1990 and 1999. Mean age was 45 years (range, 34 to 56
      years). Fourteen patients had combined liver and kidney cystic disease, but only
      1 patient required combined liver and kidney transplantation, whereas 13 patients
      underwent OLT alone. Two patients had isolated PLD. Indications for
      transplantation were massive hepatomegaly causing physical handicaps (n = 16),
      social handicaps (n = 16), malnutrition (n = 4), and cholestasis and/or portal
      hypertension (n = 5). OLT caused no technical difficulty in 15 of 16 patients
      (surgery duration, 6.8 hours; range, 5 to 8 hours), with blood transfusions of
      7.9 units (range, 0 to 22 units). One patient who underwent attempted liver-mass
      reduction pre-OLT died of bleeding and pulmonary emboli. Native liver weight was
      10 to 20 kg. Posttransplantation immunosuppression consisted of cyclosporine or
      FK506, azathioprine, and steroids (discontinued at 3 months). Morbidity included
      biliary stricture (2 patients), revision for bleeding and hepatitis (1 patient),
      pneumothorax and subphrenic collection (1 patient), and tracheostomy (1 patient).
      One patient died of lung cancer 6 years posttransplantation. Both patient and
      graft survival rates are 87.5% (follow-up, 3 months to 9 years). Of 15 patients
      who underwent OLT alone, only 1 patient needed a kidney transplant 4 years after
      OLT. Kidney function has remained satisfactory in the other patients despite the
      use of cyclosporine or FK506 (last follow-up creatinine level, 1.55 mg/dL; range,
      0.80 to 2.85 mg/dL). OLT had a dramatic impact on daily quality of life, enabling
      these patients to go back to a fully active life style. OLT offers the chance of
      a definitive treatment in patients with extensive, small, diffuse PLD that has
      evolved into severely handicapping hepatomegaly. In contrast to previous studies,
      combined liver and kidney transplantation is rarely needed. Patient symptoms and
      chances of definitive palliation offered by OLT must be balanced against the
      risks of transplantation and lifelong commitment to immunosuppression.

PMID- 11244167
TI  - Prognostic model for early acute rejection after liver transplantation.
AB  - Hepatic graft rejection is a common complication after liver transplantation
      (LT), with a maximum incidence within the first weeks. The identification of high
      risk patients for early acute rejection (EAR) might be useful for clinicians. A
      series of 133 liver graft recipients treated with calcineurin inhibitors was
      retrospectively assessed to identify predisposing factors for EAR and develop a
      mathematical model to predict the individual risk of each patient. The incidence
      of EAR (< or =45 days after LT) was 35.3%. Multivariate analysis showed that
      recipient age, underlying liver disease, and Child's class before LT were
      independently associated with the development of EAR. Combining these 3
      variables, the following risk score for the development of EAR was obtained: EAR
      score [F(x)] = 2.44 + (1.14 x hepatitis C virus cirrhosis) + (2.78 x immunologic
      cirrhosis) + (2.51 x metabolic cirrhosis)--(0.08 x recipient age in years) +
      (1.65 x Child's class A) [corrected]. Risk for rejection = e(F(x))/1 + e(F(x)).
      The combination of age, cause of liver disease, and Child's class may allow us to
      predict the risk for EAR.

PMID- 11244168
TI  - Role of cytokine gene polymorphisms in acute rejection and renal impairment after
      liver transplantation.
AB  - Although immunosuppressive regimens are effective, rejection occurs in up to 50%
      of patients after orthotopic liver transplantation (OLT), and there is concern
      about side effects from long-term therapy. Knowledge of clinical and
      immunogenetic variables may allow tailoring of immunosuppressive therapy to
      patients according to their potential risks. We studied the association between
      transforming growth factor-beta, interleukin-10, and tumor necrosis factor alpha
      (TNF-alpha) gene polymorphisms and graft rejection and renal impairment in 121
      white liver transplant recipients. Clinical variables were collected
      retrospectively, and creatinine clearance was estimated using the formula of
      Cockcroft and Gault. Biallelic polymorphisms were detected using polymerase chain
      reaction-based methods. Thirty-seven of 121 patients (30.6%) developed at least 1
      episode of rejection. Multivariate analysis showed that Child-Pugh score (P
      =.001), immune-mediated liver disease (P =.018), normal pre-OLT creatinine
      clearance (P =.037), and fewer HLA class 1 mismatches (P =.038) were
      independently associated with rejection. Renal impairment occurred in 80% of
      patients and was moderate or severe in 39%. Clinical variables independently
      associated with renal impairment were female sex (P =.001), pre-OLT renal
      dysfunction (P =.0001), and a diagnosis of viral hepatitis (P =.0008). There was
      a significant difference in the frequency of TNF-alpha-308 alleles among the
      primary liver diseases. After adjustment for potential confounders and a
      Bonferroni correction, the association between the TNF-alpha-308 polymorphism and
      graft rejection approached significance (P =.06). Recipient cytokine genotypes do
      not have a major independent role in graft rejection or renal impairment after
      OLT. Additional studies of immunogenetic factors require analysis of large
      numbers of patients with appropriate phenotypic information to avoid population
      stratification, which may lead to inappropriate conclusions.

PMID- 11244169
TI  - Orthotopic liver transplantation for biliary papillomatosis.

PMID- 11244170
TI  - Hepatic involvement in hereditary hemorrhagic telangiectasia: an unusual
      indication for liver transplantation.
AB  - Hereditary hemorrhagic telangiectasia (HHT) is a vascular disease with multiple
      organ manifestations. Severe hepatic involvement is an unusal indication for
      liver transplantation. We report on a 39-year-old woman diagnosed with HHT and
      decompensation of the disease during her second pregnancy. After delivery,
      hemobilia occurred, followed by severe therapy-resistant cholangitis and
      progressive liver dysfunction. Because of progressive loss of liver function,
      orthotopic liver transplantation needed to be performed. The various aspects of
      liver involvement in Osler's disease, diagnosis, and therapy are discussed.

PMID- 11244171
TI  - Right hepatic lobectomy as a liver graft-saving procedure.
AB  - Retransplantation is common after liver transplantation (LT). However, in the
      present era of organ shortages, every attempt to save the liver graft should be
      performed before considering retransplantation. We report our experience with
      right hepatic lobectomy (RHL) for liver graft salvage. In a retrospective series
      of 180 adult LTs, 4 patients underwent RHL (Couinaud's segments V, VI, VII, VIII)
      in the post-LT period. In all cases, the procedure was performed without
      Pringle's maneuver or mobilization of the left liver lobe to preserve its
      vascularization. Three liver graft recipients developed intrahepatic biliary
      strictures, mainly localized to the right lobe of the graft, and RHL was
      performed 14, 75, and 78 months after LT. These patients were alive at last
      follow-up without further episodes of cholangitis or retransplantation (mean
      follow-up, 38 months). The fourth patient developed early post-LT right liver
      necrosis with a functioning hepatic artery and underwent right lobectomy 48 hours
      after LT. He later developed cholangitis secondary to late hepatic artery
      thrombosis, requiring retransplantation after 18 months. We conclude that RHL can
      be considered a graft-saving option in selected liver transplant recipients with
      localized biliary strictures, with excellent patient and graft survival.

PMID- 11244172
TI  - Acute changes in cerebral blood flow and metabolism during portasystemic
      shunting.
AB  - This report describes the instantaneous changes in cerebral blood flow (CBF),
      determined by intravascular ultrasound and Doppler, in a patient with cirrhosis
      undergoing placement of a transjugular intrahepatic stent-shunt for uncontrolled
      variceal bleeding. Acute changes in CBF were observed during and after
      portasystemic shunting, which culminated in cerebral edema and cerebral
      herniation.

PMID- 11244173
TI  - The real danger of lamivudine-resistant hepatitis B virus infection in the
      immunocompromised host.

PMID- 11244174
TI  - Reliability of the health utilities index-Mark 2 and its applicability to
      survivors of orthotopic liver transplantation.

PMID- 11244175
TI  - Liver-splitting terminology.

PMID- 11244176
TI  - Discussion.

PMID- 11244177
TI  - Discussion.

PMID- 11244178
TI  - Discussion.

PMID- 11244179
TI  - Discussion.

PMID- 11244180
TI  - Discussion.

PMID- 11244181
TI  - Metabolic transit and in vivo effects of melanoidins and precursor compounds
      deriving from the Maillard reaction.
AB  - Metabolic transit data on food-borne advanced MRPs (Maillard reaction products)
      termed melanoidins are yet not completely elucidated and it is still an open
      question whether isolated melanoidin structures undergo metabolic
      biotransformation and subsequently cause physiological effects in vivo. Advanced
      MRPs, acting as premelanoidins, and melanoidins are formed under severe heat
      treatment of foods and are ingested with the habitual diet at considerable
      amounts. Metabolic transit data are known for Amadori compounds classified as
      early MRPs, like, e.g., fructose-lysine. For rats and humans, the percentages of
      ingested free versus protein-bound fructose-lysine excreted in the urine were
      found within ranges of 60-80% and 3-10%, respectively. Balance studies on free
      advanced MRPs are still lacking, but protein-bound low-molecular-weight
      premelanoidins and high-molecular-weight melanoidins have already been
      investigated in animal experiments using (14)C-tracer isotopes. The amount of
      ingested radioactivity absorbed and excreted in the urine was found at levels
      ranging from 16 to 30% and from 1 to 5% for premelanoidins and melanoidins,
      respectively. These different metabolic transit data of premelanoidins and
      melanoidins can be explained by the following mechanisms involved: (i) intestinal
      degradation by digestive and microbial enzymes; (ii) absorption of these
      compounds or their degradates, and (iii) tissue retention. Structure specific in
      vivo effects have been identified for protein-bound premelanoidins on intestinal
      microbial activity, xenobiotic biotransformation enzymes and further glycation
      reactions. The latter are hypothesized to be involved in the aging process and in
      the course of different diseases. Further investigations are needed to clarify
      synergistic in vivo effects of dietary ingested melanoidins and endogenously
      formed glycation products.

PMID- 11244182
TI  - Influence of a probiotic yoghurt on the status of vitamins B(1), B(2) and B(6) in
      the healthy adult human.
AB  - BACKGROUND/AIMS: The main reason for this study was to determine whether yoghurt
      bacteria, being rich in some water-soluble vitamins, release them or utilize
      vitamins from their surroundings. Our study was trying to determine for the first
      time, if the viable bacteria of probiotic yoghurt are able to influence the
      parameters of the B-vitamin (B(1), B(2), B(6)) status of the healthy adult human.
      METHODS: The test yoghurt was commercially available probiotic yoghurt prepared
      with Streptococcus thermophilus and Lactobacillus acidophilus, enriched with
      Lactobacillus casei GG. Different chemical forms of all investigated B-vitamins
      were determined by HPLC methods. In order to determine the influence of the
      yoghurt flora, each of 12 subjects consumed four yoghurt portions 125 g each ( =
      500 g) a day, containing thermally inactivated cultures during the first 2-week
      period and yoghurt without heat treatment during the second 2-week period.
      RESULTS: The heat treatment of the probiotic yoghurt caused negligible changes in
      vitamin contents. The plasma levels of thiamin decreased significantly (p < 0.01)
      after the first 2-week period and kept on decreasing during the second 2-week
      period. A similar trend was found in the urinary excretion. The plasma levels of
      the B(2)-vitamers were different. The flavin adenine dinucleotide concentrations
      increased significantly (p < 0.01) after the consumption of heat-treated yoghurt
      and decreased significantly (p < 0.05) after the following 2 weeks, in which the
      subjects received the untreated yoghurt. In contrast, the flavin mononucleotide
      plasma levels decreased during the first 2-week period and increased during the
      second part of the study, but the change was not statistically significant. The
      free riboflavin concentrations in plasma and urine showed a continuous but not
      significant increase. The concentrations of pyridoxal-5-phosphate in plasma
      increased after the consumption of yoghurt with the inactivated bacteria and
      decreased in the second part of the study. However, the differences were not
      significant. The excretion of thiamin, B(2)- and B(6)-vitamers in the faeces did
      not significantly change throughout the study period (p>0.05). CONCLUSIONS: Our
      observations show that the bacterial flora of the examined yoghurt does not
      influence the vitamin B(1), B(2) and B(6) status of man. It seems likely that
      even lactobacilli of the 'probiotic' type which are vitamin B consumers can
      decrease the bioavailability of these vitamins for man. Obviously a thermal death
      of the cells did not induce a release of physiologically active vitamins.

PMID- 11244183
TI  - Protein quality evaluation in rats of typical diets for 4- to 6-year-old children
      from different socioeconomic areas living in Oaxaca, Mexico.
AB  - Legumes and cereals are principal sources of energy and protein in developing
      countries. In Oaxaca, Mexico, corn is the primary agricultural crop, therefore
      corn tortillas and beans are the main energy and protein sources. The objective
      of this study was to evaluate the protein quality in rats of typical diets for 4-
      to 6-year-old children from different socioeconomic areas in Oaxaca, Mexico.
      Composite diets representing the typical diets were formulated and fed to male
      weanling rats for 10 days. A control diet using casein as the reference diet and
      one free of nitrogen were included in the study. The apparent protein
      digestibility was determined in rats using the chromic oxide marker technique and
      the data was statistically analyzed for differences between control and
      experimental diets. Rats fed the diet of low income children gained about 2 g/day
      compared to about 3.8 g/day for the rats fed the control (casein) diet and had
      the lowest weight gain/g of protein intake. The NPR was 3.52 compared to 4.31 for
      the control diet. This diet is 67% vegetable protein and 33% animal protein. The
      diet for the medium income group contained a higher percentage of animal protein,
      76% and thus higher digestibility, 78%. The results of this study indicate that
      the protein quality of children's diets in Oaxaca, Mexico, need to be improved.

PMID- 11244184
TI  - In situ metabolic and hemodynamic response to dexfenfluramine in white adipose
      tissue of rats.
AB  - Serotonergic neurons are included in the regulation of eating behavior and energy
      metabolism. Dexfenfluramine (DF), a serotonin releaser and reuptake inhibitor, is
      known to reduce food intake and body weight and to improve the metabolic profile
      of obese subjects with and without metabolic complications such as type 2
      diabetes. Due to cases of valvular heart diseases, DF was withdrawn from the
      market in 1997. However, serotonergic drugs are still used in clinical practice.
      We studied the hemodynamic and metabolic changes induced by in situ perfusion of
      inguinal subcutaneous adipose tissue (SAT) of normal-weight rats with either 1
      microM isoproterenol (IP) or 5 microM DF using the microdialysis technique.
      Perfusion of SAT with IP resulted in an increase in blood flow (+25%) and
      lipolysis (+35%) when compared to baseline. In contrast to that, perfusion of SAT
      with DF resulted in a decrease in blood flow (-25%) and lipolysis (-35%).
      Additionally, dialysate glucose was decreased and dialysate lactate was increased
      during perfusion with DF, indicating stimulation of glucose uptake and the
      glycolytic pathway. It is concluded that DF reduces blood flow and lipolysis
      whereas it stimulates the glycolytic pathway in SAT and that this could
      contribute to the positive metabolic outcome, i.e., lowered blood lipids and fat
      mass of DF-treated obese subjects.

PMID- 11244185
TI  - Effects of long-chain monounsaturated and n-3 fatty acids on fatty acid oxidation
      and lipid composition in rats.
AB  - Long-chain n-3 fatty acids and fat fish are reported, among multiple
      physiological properties, to enhance peroxisomal beta-oxidation and effect
      triacylglycerol status. Long-chain n-3 and monounsaturated fatty acids are the
      main portion of fatty acids in fat fish. The individual effect of long-chain
      monounsaturated fatty acids on beta-oxidation and fatty acid composition was
      tested and compared to the effect of n-3 polyunsaturated and saturated fatty
      acids in a 3-week feeding experiment of rats. To explore the contribution from
      long-chain monounsaturated fatty acids in these aspects, the effect of long-chain
      n-3 and monounsaturated fatty acids on mitochondrial and peroxisomal beta
      oxidation was compared, as well as fatty acid composition of adipose tissue,
      liver and serum. Fatty acid oxidase, palmitoyltransferase I and II activities,
      the amount of serum lipids, and the fatty acid composition of lipid fractions
      from the organs were analysed. The peroxisomal beta-oxidation was enhanced by the
      n-3 fatty acids, whereas a small, significant increase with the monounsaturated
      fatty acids was observed. There was a stimulation of the mitochondrial oxidation
      with the n-3 fatty acids, but monounsaturated fatty acids gave a small,
      nonsignificant decrease. With n-3 fatty acids there was a considerable decrease
      in the levels of serum triacylglycerol, phospholipids, free fatty acids and total
      cholesterol, while there were only minor effects of monounsaturated fatty acids.
      As judged from the fatty acid composition data, there was a mobilization on n-3
      fatty acids from the adipose tissue to liver and plasma with the n-3 diet. This
      observation was also seen with the monounsaturated fatty acid-enriched diet. In
      conclusion, monounsaturated fatty acids seemed to stimulate peroxisomal beta
      oxidation and to increase plasma triacylglycerol, whereas the mitochondrial
      oxidation was slightly decreased.

PMID- 11244186
TI  - Casein and soy protein isolate in experimental atherosclerosis: influence on
      hyperlipidemia and lipoprotein oxidation.
AB  - BACKGROUND/AIMS: Nutrients able to modify the susceptibility of lipoproteins to
      oxidation and/or reduce the cholesterol levels of blood plasma are important for
      prevention and/or treatment of atherosclerosis. The influence of animal and
      vegetable proteins on hypercholesterolemia and atherogenesis has been studied,
      concerning the mechanisms able to modify the digestion, absorption and
      bioavailability of lipids. In this study, the influence of casein and soy protein
      isolate on lipoprotein oxidation and atherosclerosis progression was investigated
      in cholesterol-fed rabbits. METHODS: During 2 months, 20 New Zealand rabbits were
      fed with diets containing 1% cholesterol and 27% casein or 27% soy protein
      isolate. Blood samples were collected at baseline, 15, 30, 45 and 60 days of
      feeding. RESULTS: Casein feeding contributed to increasing cholesterol and
      triglyceride concentrations, lipoprotein oxidation and the area of aorta
      atherosclerotic lesions. In contrast, the soy protein isolate reduced, when
      compared to casein, the concentrations of cholesterol and lipid peroxides of beta
      VLDL and LDL fractions during the experimental time course, as well as the area
      of atherosclerotic lesions at the end of the study. CONCLUSION: Soy protein
      isolate, in comparison with casein, promoted a decrease of lipid peroxides,
      cholesterol and triglyceride content of atherogenic lipoproteins (beta-VLDL and
      LDL), which had beneficial effects over atherosclerosis progression in
      cholesterol-fed rabbits.

PMID- 11244187
TI  - Using artificial intelligence to predict the equilibrated postdialysis blood urea
      concentration.
AB  - Total dialysis dose (Kt/V) is considered to be a major determinant of morbidity
      and mortality in hemodialyzed patients. The continuous growth of the blood urea
      concentration over the 30- to 60-min period following dialysis, a phenomenon
      known as urea rebound, is a critical factor in determining the true dose of
      hemodialysis. The misestimation of the equilibrated (true) postdialysis blood
      urea or equilibrated Kt/V results in an inadequate hemodialysis prescription,
      with predictably poor clinical outcomes for the patients. The estimation of the
      equilibrated postdialysis blood urea (eqU) is therefore crucial in order to
      estimate the equilibrated (true) Kt/V. In this work we propose a supervised
      neural network to predict the eqU at 60 min after the end of hemodialysis. The
      use of this model is new in this field and is shown to be better than the
      currently accepted methods (Smye for eqU and Daugirdas for eqKt/V). With this
      approach we achieve a mean difference error of 0.22 +/- 7.71 mg/ml (mean % error:
      1.88 +/- 13.46) on the eqU prediction and a mean difference error for eqKt/V of 
      0.01 +/- 0.15 (mean % error: -0.95 +/- 14.73). The equilibrated Kt/V estimated
      with the eqU calculated using the Smye formula is not appropriate because it
      showed a great dispersion. The Daugirdas double-pool Kt/V estimation formula
      appeared to be accurate and in agreement with the results of the HEMO study.

PMID- 11244188
TI  - Very high daily intraperitoneal doses of carbonyl compounds affect the
      morphology, but not the exchange characteristics, of rat peritoneum.
AB  - Glucose degradation products (GDP) are carbonyl compounds, that are formed by
      heat sterilization of conventional peritoneal dialysis (PD) fluids. Carbonyl
      compounds are known to be toxic in vitro and potentially toxic also in vivo. The
      aim of this study was to evaluate the effects of daily, short-term exposure of
      the peritoneum to very high concentrations of GDP in vivo on peritoneal transport
      parameters and on peritoneal morphology in a well-established rat model of PD.
      Rats were exposed to three daily intraperitoneal (IP) injections (10 ml) for 9
      days of a largely neutral (pH 7.2) PD fluid containing 1.5% glucose and
      sterilized by filtration, with (n = 8) or without (n = 8) the presence of
      different carbonyl compounds in concentrations 100 times higher than those
      reported in commercial PD fluids. Seven rats, not subjected to any exposure,
      served as controls. After the exposure, the rats were subjected to acute PD in 4
      hour dwells. Twenty milliliters of 4% glucose dialysis fluid were instilled into
      the rat peritoneal cavity. Blood and dialysate samples were taken during the
      dwell for measurements of dialysate sodium, and for assessments of the mass
      transfer area coefficient (PS) for glucose and 51Cr-EDTA and of transperitoneal
      clearance (Cl) or radiolabelled albumin (RISA). At the end of the dwell, parts of
      the liver, diaphragm and peritoneum were removed for measurements of tissue cell
      density and thickness of the submesothelial peritoneal tissue. The exposure of
      the peritoneum to very high doses of carbonyl compounds did not affect the
      peritoneal transport of fluid and small solutes significantly, but seemed to
      slightly reduce lymph flow and albumin clearance out of the peritoneal cavity.
      Assessed after a hypertonic dwell, and compared to the situation in nontreated
      rats after the same kind of dwell, there was a significant thinning of the
      submesothelial tissue, but no difference in tissue cell density. It is concluded
      that short-term exposure of the peritoneum in vivo to very high doses of GDP
      resulted in almost no signs of acute toxicity.

PMID- 11244189
TI  - A Comparative Study of Blood Pressure Control with Short In-Center versus Long
      Home Hemodialysis.
AB  - We conducted a randomized crossover trial to establish, within patients, whether
      long-slow hemodialysis (HD) was associated with better blood pressure (BP)
      control than standard HD. Nine home HD patients, not on antihypertensive drugs,
      were dialyzed to the same eKt/V(urea) and target weights for 6-8 h (LD) at home
      and for 3.5-4.5 h (SD) in the dialysis center 3 times weekly in randomized
      sequence, with each phase lasting 8 weeks. Ambulatory BP, bioimpedance,
      neurohormones and autonomic function were measured in each phase. Pre- and
      postdialysis systolic, ambulatory systolic and diastolic BP were all higher with
      SD than with LD and intradialysis hypotension was more common. Weight, ECF volume
      and neurohormones did not differ between treatments. Muscle sympathetic activity
      was increased in both phases and cardiac sympathetic activity tended higher
      during SD. These findings suggest that additional factors to ECF volume may
      contribute to the superior BP control produced by long-slow HD.

PMID- 11244191
TI  - Familial homozygous hypercholesterolemia: effective long-term treatment with
      cascade double filtration plasmapheresis.
AB  - BACKGROUND: Homozygous familial hypercholesterolemia (FH) is a rare disease with
      an incidence of 1 in 1 million births. It is characterized by blood cholesterol
      levels over 600 mg/dl and the development of extensive cutaneous xanthomata
      before the age of 5. Severe premature coronary artery disease results in fatal
      myocardial infarctions within the first two decades of life. The absence of LDL
      receptors makes homozygous FH resistant to treatment with most HMG-CoA reductase
      inhibitors, and alternative methods of removing cholesterol have been employed.
      METHODS: We used the ASAHI plasauto-IQ double filtration cascade plasmapheresis
      to treat 2 young brothers aged 14 and 11 years and 6 months for 5 years and 1
      month and 3 years and 10 months, respectively. The elder brother has received 136
      double filtration treatments at 2-week intervals and the younger brother 100 such
      treatments without complications. RESULTS: During the period of treatment the
      average pretreatment total serum cholesterol level for patient 1 was 442 mg/dl.
      The average posttreatment value was 163 mg/dl. The average fall in total serum
      cholesterol with each treatment was 63.2%. The mean total serum cholesterol for
      all the periods of treatment was calculated at 303 mg/dl. For the 2nd patient,
      the average pretreatment value of total serum cholesterol was 435 mg/dl. The
      posttreatment value was 124 mg/dl and the average fall 71.5%. The calculated mean
      total serum cholesterol for all periods of treatment was 280 mg/dl. CONCLUSIONS:
      Double filtration cascade plasmapheresis at 2-week intervals provides an
      effective and safe long-term treatment for patients with homozygous FH. The
      achieved reduction in serum cholesterol allows complete resolution of cutaneous
      xanthomata, arrests previous atherosclerosis, and prolongs normal life.

PMID- 11244190
TI  - Long-term on-line hemodiafiltration reduces predialysis beta-2-microglobulin
      levels in chronic hemodialysis patients.
AB  - BACKGROUND: Hemodiafiltration (HDF) is effective in delaying the surgical need
      for carpal tunnel syndrome in chronic hemodialysis patients, however, predialysis
      beta(2)-microglobulin levels were not reduced in most short-term studies. The aim
      of this study was to assess the effect of long-term and differing frequencies of
      on-line HDF on serum beta(2)-microglobulin levels in comparison to high-flux
      hemodialysis (HD). METHODS: One hundred and twelve patients in the Chang Gung
      Memorial Hospital Dialysis Unit were divided into three groups to receive
      different frequencies of on-line HDF alternating with high-flux HD. Group 1 was
      treated once with HDF and twice with high-flux HD per week (n = 21). Group 2 was
      treated twice with HDF and once with high-flux HD per week (n = 33). Group 3 was
      treated with HDF three times per week (n = 58). Analysis was performed to compare
      the serum beta(2)-microglobulin levels in these groups and to high-flux HD.
      RESULTS: After receiving HDF for a mean of 7.9 months, group 3 patients had a
      reduced predialysis beta(2)-microglobulin level (22.2 +/-5.3 vs. 34.8 +/-6.3
      mg/l, p < 0.001), postdialysis beta(2)-microglobulin level (6.3 +/- 2.0 vs. 13.8
      +/- 6.8 mg/l, p < 0.001) and an increased beta(2)-microglobulin reduction rate
      (76.1 +/- 5.6 vs. 61.1 +/- 13.3%, p = 0.03) when compared to high-flux HD. A
      significant improvement in URR (p = 0.0004), Kt/V (p = 0.0002) and TAC urea
      levels (p = 0.006) but not nPCR (p = 0.122) was found after patients had been
      treated with on-line HDF. The beta(2)-microglobulin reduction rate was positively
      correlated with the overall volume of the replacement solution per session (p <
      0.0001). Patients in group 3 had lower predialysis beta(2)-microglobulin levels
      than those in group 1 and group 2 (22.2 +/- 5.3 vs. 25.2 +/- 7.2 vs. 26.0 +/- 4.2
      mg/l, p = 0.02). Furthermore, an inverse correlation was found between the
      predialysis beta(2)-microglobulin level and the duration of HDF, if patients were
      treated for more than 12 months (p = 0.031). CONCLUSION: On-line HDF has an
      increased dialysis efficiency compared to high-flux dialysis. Long-term HDF
      further reduced predialysis beta(2)-microglobulin levels, thus, it may provide an
      improved modality for renal replacement therapy.

PMID- 11244192
TI  - Proinflammatory cytokines in heart disease.
AB  - Proinflammatory cytokines affect nearly all tissues and organ systems, and the
      vasculature is no exception. Although a considerable amount of research has
      focused on the role of the two most prominent proinflammatory cytokines,
      interleukin-1 (IL-1) and tumor necrosis factor (TNF), in the pathogenesis of
      sepsis and septic shock, the role of these and other cytokines in the
      pathogenesis of atherosclerotic lesions of the coronary artery, the acute
      ischemic event associated with myocardial infarction, the progression of
      myocardiopathies or the loss of myocardial function in congestive heart failure
      is a relatively recent discovery. Moreover, there has also been significant
      investigation of the cardioprotective effects of cytokines. Most of the attention
      has focused on the acute coronary syndromes and the myocardial suppression that
      takes place as a result of acute ischemia. The potential for anticytokine-based
      therapies in treating heart disease is great. Parenteral TNF-alpha neutralization
      and IL-1 receptor blockade are presently used to treat rheumatoid arthritis. Two
      orally effective agents, the IL-1beta-converting enzyme inhibitor and the mitogen
      activating protein kinase p38 inhibitor, are currently being investigated in
      clinical trials.

PMID- 11244193
TI  - Xenotransplantation: perspectives and limits.
AB  - Xenotransplantation faces the dilemma of an unlimited supply of cells, tissues
      and organs on the one hand and severe obstacles and limits on the other. One
      reason for the limitations is that the source animal of choice, the pig, and the
      human recipient separated 90 million years ago during evolution, a time in which
      biological characteristics such as anatomy, physiology and immunology have had
      much time to drift far apart. The acceptance of such an evolutionary widely
      divergent organ, especially the heart of a pig, could evoke refusal of
      xenotransplantation in conservative and religious patients. New legal aspects of
      allocation of xenografts have therefore to be reflected upon and appropriate
      guidelines developed. Inquiries show, however, that the acceptance of all types
      of porcine organs would be high if the quality of life after receiving such a
      xenograft is comparable to that after receiving the same allograft. This
      individual benefit of a xenograft could lead to a disregard of the collective
      risk in terms of xenozoonoses, often presented as a catastrophic scenarium.
      Therefore, transplantation societies and ethics committees have published
      comments and even guidelines for handling future clinical xenotransplantation.
      All three monotheistic religions and Hinduism support the idea of saving and
      improving human life with the help of an animal organ.

PMID- 11244194
TI  - Perfusion thresholds in human cerebral ischemia: historical perspective and
      therapeutic implications.
AB  - After middle cerebral artery occlusion (MCAO) in the laboratory animal, the
      ischemic penumbra has been documented as a severely hypoperfused, functionally
      impaired, but still viable cortex which can regain its function and escape
      infarction if it is reperfused before a certain time has elapsed. The penumbra
      surrounds the ischemic core of already irreversibly damaged tissue, and is
      progressively recruited into the core with increasing MCAO duration. In the
      animal, the threshold of cerebral blood flow (CBF) below which neuronal function
      is impaired and the tissue is at risk of infarction is around 22 ml/100 g/min
      (approximately 40% of normal) in the awake or lightly anesthetized monkey, and
      around 30--35 ml/100 g/min in the cat and the rat. The threshold of CBF below
      which the tissue becomes irreversibly damaged and will progress to infarction
      depends on the duration of ischemia, and is around 10 ml/100 g/min for 1--2 h
      (approximately 20% of normal) and around 18 ml/100 g/min for permanent ischemia
      in the monkey. Mildly reduced CBF down to the 40% threshold (termed 'oligemia')
      is normally well tolerated, and the affected tissue is not at risk of infarction
      under uncomplicated conditions (in the animal, however, selective neuronal death
      may occur even with only mildly reduced CBF values, but this sequela of stroke
      seems an exceptional encounter in man). Classic studies with carotid artery
      clamping in man have provided estimates for the penumbra threshold at around 20
      ml/ 100 g/min for the whole brain, but only recently have imaging studies allowed
      to document the existence of the penumbra in acute stroke and given estimates of
      local CBF thresholds. With PET, the penumbra is characterized by a reduced CBF,
      an increased oxygen extraction fraction, and a relatively preserved oxygen
      consumption (CMRO(2)). In a series of PET studies performed 5--18 h after stroke
      onset, we have determined the threshold for penumbra to be around 20 ml/100
      g/min, and documented that the extent of neurological recovery is proportional to
      the volume of penumbra that eventually escaped infarction. Within this time
      interval, the thresholds for irreversible damage were around 8 ml/ 100 g/min for
      CBF and around 0.9 ml/100 g/min for CMRO(2). Recent studies with diffusion
      weighted and perfusion MR have reported similar relative thresholds for CBF of
      about 50 and 18% for penumbra and core, respectively. Although it is likely that
      the threshold for irreversibility will be lower with shorter duration since
      clinical onset, this has not been documented thus far. Because saving the
      penumbra will improve clinical outcome, it should constitute the main target of
      acute stroke therapy. We found evidence of penumbra in about one third of the
      cases studied between 5 and 18 h after onset, and as late as 16 h after symptom
      onset in occasional patients, suggesting the therapeutic window may be protracted
      in at least a fraction of the cases; similar experience has recently accrued from
      diffusion-weighted MR and perfusion MR. In the remaining patients, there was
      evidence of early extensive damage or early spontaneous reperfusion, which would
      make them inappropriate candidates for neuroprotective therapy. Recent evidence
      from PET studies of relative perfusion performed within 3 h of onset suggests
      that early thrombolysis indeed saves the tissue with CBF below a critical
      threshold of 12 ml/ 100 g/min, with a correlation between the volume of such
      tissue escaping infarction and subsequent neurological recovery. Thus, mapping
      the penumbra in the individual patient with physiologic imaging should allow to
      formulate a pathophysiological diagnosis, and in turn to design a rational
      management of the stroke patient and to increase the sensitivity of drug trials
      by appropriate patient selection.

PMID- 11244195
TI  - Automated three-dimensional signature model for assessing brain injury in
      emergent stroke.
AB  - This presentation will focus on the value of established and newer MR methods
      that can be applied to the diagnosis and management of ischemic stroke with
      emphasis on future applications of MR to provide previously unmet needs of the
      treating clinician and clinical trials. Time alone is an inadequate indicator of
      the therapeutic window, especially when the time of stroke onset is uncertain.
      Thus, there is a need to predict the evolution of stroke in a way that more
      precisely and with greater resolution identifies the progression of cellular
      damage at the moment of investigation. This also would be of value for
      thrombolysis when knowledge of the degree and extent of tissue necrosis and the
      consequent potential for brain hemorrhage is of the utmost importance. To provide
      this, we perform postprocessing of diffusion-, T(1)- and T(2)-weighted images to
      produce the apparent diffusion coefficient of water, and T(1) and T(2) maps that
      are then further processed to provide maps and quantitation of the tissue
      signatures of ischemic histopathology. By these means, we can accomplish
      objective volumetric analysis of infarct size and of the proportions of
      potentially viable and salvageable tissue. We will show how this has the
      potential to predict long-term stroke outcome and facilitate decision-making in
      terms of safety of reperfusion strategies and the appropriateness of
      cytoprotective treatment. The value of our approach is to replace time as the
      therapeutic window and extend the opportunity of treatment to those patients
      presenting beyond the stringent time limits employed in current investigative
      clinical trials. Further, used as a surrogate marker of clinical outcome, this
      form of stroke analysis may speed proof of principle clinical trials in small
      numbers of stroke patients.

PMID- 11244196
TI  - Neurosonology in cerebral ischemia: future application of transcranial Doppler in
      acute stroke.
AB  - Transcranial Doppler (TCD) has become a general practice in recent years in the
      diagnostic study of patients with cerebral ischemia. This is due to the fact that
      it is a rapid, noninvasive, reproducible and dynamic examination of intracranial
      circulation. In the acute phase of cerebral infarction, it can detect MCA
      occlusion with a good correlation with angiographic findings and, what is even
      more important, the patients who will later suffer lacunar infarctions almost
      always show a normal Doppler examination. Acute abnormalities can also
      demonstrate the mechanism of the clinical signs; the examination informs us of
      the existence of collaterals and severe occlusions or stenoses of the
      extracranial arteries, and can change the priority in the search for the
      etiological diagnosis. The diagnosis of intracranial stenoses as a cause of
      clinical signs is another immediate application of TCD, right from the acute
      phase. If in the future anticoagulation is shown to be an optimum treatment for
      secondary prophylaxis in intracranial stenoses, TCD will probably become the
      diagnostic technique of choice. The ability to predict the prognosis based on
      parameters obtained by TCD opens up the possibility of using it as an auxiliary
      technique for the selection of patients for reperfusion treatment, having in its
      favor that it is quick and easy to perform, and therefore suitable for treatment
      monitoring. It seems clear that the data obtained by Doppler in the first 6 h are
      a good predictor of both spontaneous improvement and early impairment, which
      could help to avoid treatment in patients in whom a rapid improvement can be
      expected. Finally, the hemodynamic data of the TCD could be of inestimable value
      in the assessment and monitoring of intracranial hypertension treatments and for
      hemodynamic management of the patient, allowing the treatment margins of the
      acute phase of arterial hypertension to be reliably established without
      compromising the perfusion pressure. In conclusion, TCD will possibly be more
      widely used in the future in the acute phase of cerebral infarction as a guide to
      diagnostic procedures, for treatment selection and for monitoring of cerebral
      hemodynamics.

PMID- 11244197
TI  - Cerebral ischemia: from animal studies to clinical practice. Should the methods
      be reviewed?
AB  - The development of experimental models of focal cerebral ischemia has allowed for
      a better knowledge of its pathophysiology and for testing therapeutic strategies.
      However, most neuroprotective substances giving favorable results in these models
      have later not been shown to be clinically effective. This could be explained by
      several reasons. First, the homogeneity obtained in animal models in order to
      achieve results is not seen in clinical practice in humans, in whom a given
      pathological condition may show a high variability depending on several
      parameters. This makes it difficult to achieve groups of patients sufficiently
      large and homogeneous to obtain valid conclusions in the clinical trials. The
      lack of agreement between the experimental studies and the clinical practice can
      also be explained by other reasons, such as the methods of the experimental model
      itself; by the fact that the methods to assess results in these models are not
      comparable to those used in clinical practice; by pathophysiological differences
      between experimental animals and man, and even by the fact that the substances
      tested have different pharmacological properties in the different species. These
      disadvantages must not invalidate preclinical neuroprotection studies. Rather,
      the knowledge of the reasons for divergences with the clinical situation can help
      to optimize experimental models so that both become actually comparable, and the
      laboratory results can be confirmed by clinical studies.

PMID- 11244198
TI  - Acute care in stroke: do stroke units make the difference?
AB  - The consideration of stroke as a medical emergency and the development of new
      specific treatments to be applied in a narrow therapeutic window have shown the
      need to establish an adequate organization system for the management of stroke.
      It should be considered as an integral process both outside and inside the
      hospital. General care is essential and must already start outside the hospital,
      and comprises respiratory and cardiac care, fluid and metabolic management,
      especially blood glucose control, avoiding the administration of glucose
      solutions, blood pressure control, early treatment of hyperthermia and prevention
      and treatment of neurologic and systemic complications. In the early 70s, the
      first stroke units (SU) were established as intensive-care SU, but failed to show
      improvement in terms of reduction of mortality-morbidity. Nowadays, the concept
      has changed to a non-intensive-care SU. The benefit of these SU has been amply
      demonstrated in terms of reduction in mortality and in long institutionalization,
      as well as better functional outcome compared with general wards, and the
      efficacy of a neurology ward compared to a general medicine department has also
      been shown, but at the moment there are no studies analyzing the differences
      between a stroke team (ST) in a department of neurology and a SU. In this regard,
      we have performed a sequential analysis comparing both SU and ST and demonstrated
      a reduction in length of stay, complications and acute care costs with an
      improvement in functional state at hospital discharge, a reduction in the
      discharge to nursing homes with an increase in patients translated into
      rehabilitation wards. With these data, we can conclude that SU, not ST are the
      most effective organizational model for acute stroke management. Definitely, the
      SU make the difference.

PMID- 11244199
TI  - Predictors of deteriorating cerebral infarct: role of inflammatory mechanisms.
      Would its early treatment be useful?
AB  - The development of neurological deterioration in the hours following the stroke
      onset occurs in somewhat more than 1 in 3 cerebral infarcts and is associated
      with an increase in morbidity and mortality. This early deterioration (0--48/72
      h) entails the conversion of the ischemic penumbra area in an irreversible
      lesion, a process that is mediated as much by hemodynamic changes in the local
      cerebral circulation as by biochemical mechanisms. Late neurological
      deterioration (3--7 days) is more frequently associated with systemic causes.
      Knowledge of the various clinical, biochemical and imaging markers associated
      with neurological deterioration is consequently of fundamental importance. For
      their repercussion in clinical practice, we classify these predictors of
      deteriorating cerebral infarct into nonmodifiable, modifiable and possibly
      modifiable. The reduction in cerebral blood flow in a particular cerebral zone
      causes very early cerebral damage as a consequence of a significant liberation of
      neuroexcitatory amino acids, followed by an excessive entry of calcium into the
      interior of cells; this process causes lipid peroxidation, disintegration of the
      cellular membranes, nuclear destruction and neuronal death. Moreover, ischemia
      and posterior reperfusion induce an inflammatory response leading to further
      cellular destruction. It is therefore conceivable that therapeutic interventions
      aimed at decreasing proinflammatory cytokines and cell adhesion molecules might
      result in better outcome in this population.

PMID- 11244200
TI  - Antithrombotic therapy in the acute phase: new approaches.
AB  - Both anticoagulants and antiplatelet agents have been advocated, used and studied
      for the treatment of acute ischemic stroke. Randomized trials of unfractionated
      heparin, low-molecular-weight heparin and heparinoids have failed to show an
      overall benefit to these agents largely because the benefits in reducing
      thromboembolic events are offset by the increased risk of bleeding complications.
      The International Stroke Trial, the Trial of ORG 10172 Acute Stroke Treatment and
      studies of fraxaripine all failed to show an overall benefit to anticoagulation
      in the patients studied. Aspirin has been shown to offer a modest benefit when
      studied in patients treated within 48 h of stroke onset. Ancrod is an
      antithrombotic agent that acts by reducing circulating fibrinogen levels.
      Patients treated within 3 h of stroke symptom onset had a better functional
      outcome at 90 days compared to placebo-treated patients with both the benefits
      and the risk of intracerebral bleeding related to the fibrinogen lowering
      achieved. Abciximab is a blocker of the platelet GPIIb/IIIa receptor. A dose
      finding safety study suggests that in doses up to that typically given in
      patients with acute coronary occlusion syndromes, there is no increased risk of
      symptomatic intracerebral bleeding and suggestions of potential benefits on
      neurological outcome.

PMID- 11244202
TI  - Current status and perspectives of neuroprotection in ischemic stroke treatment.
AB  - In developed countries, ischemic stroke is one of the leading causes of death and
      neurological impairment. The two most important therapeutic approaches in
      patients with acute cerebral ischemia consist of improving cerebral blood flow
      and blocking the biochemical and metabolic changes at the ischemic cascade level.
      The significant advances made in the past decade in the knowledge of the
      physiopathological mechanisms of cerebral ischemia, and the development of new
      drugs have given rise to true expectations regarding treatment and the rejection
      of nihilist attitudes. In the past 15 years, based on the excellent results
      obtained in experimental models of ischemia, many clinical trials have been
      conducted with different neuroprotective drugs. The results obtained in most
      studies have been negative, or the studies were terminated early owing to side
      effects. However, some drugs (citicoline, clomethiazole, piracetam and ebselen)
      have shown a certain degree of clinical efficacy, limited to subgroups of
      patients, and with a narrow therapeutic window, longer-lasting in the case of
      citicoline. The design of new clinical trials with neuroprotective drugs requires
      adequate preclinical assessment and the use of the new magnetic resonance
      techniques for the selection of patients and the assessment of the efficacy of
      treatment. The new trends in neuroprotection in focal cerebral ischemia and the
      results of the clinical trials published to date are reviewed.

PMID- 11244201
TI  - Thrombolysis in ischaemic stroke -- present and future: role of combined therapy.
AB  - THROMBOLYSIS: ECASS I, the NINDS trial and ECASS II showed that thrombolysis with
      rt-PA is effective in acute ischaemic stroke. In ECASS I, there was a safety
      problem because of increased mortality, while the results of the NINDS trial led
      the FDA to approve the use of rt-PA in ischaemic stroke. The safety was no more a
      problem in ECASS II. A meta-analysis of those three trials revealed that
      thrombolysis decreases the risk of death and dependency. For each 1,000 patients
      treated within 3 h, there will be 140 less dead or dependent, and 90 less if the
      treatment is given within 6 h. These data support the view that rt-PA should be
      part of the management of acute ischaemic stroke within 3 h, and probably beyond,
      in selected patients and experienced centres. Thrombolysis within a 3-hour time
      frame is also likely to result in net cost savings. COMBINATION THERAPY: All
      trials studying neuroprotecting agents have failed in man, although they have
      been successful in experimental animals. A combination of thrombolysis and a
      neuroprotecting agent or a combination of two neuroprotecting agents have been
      effective in experimental stroke, but the only clinical study with combination
      therapy (rt-PA with or without lubeluzole) was terminated prematurely before the
      planned population was enrolled. This was not because of safety problems but
      because the sponsor lost interest. CONCLUSION: In future, there will most likely
      be others to challenge the strategy of the combined therapy, and this strategy
      will sooner or later lead to a benchmark breakthrough. It is unlikely that any of
      these therapies or their combinations will work without well-organised services,
      which can provide fast and efficient medical care. Without such a triage, any
      drug will be unlikely to have a major impact on stroke recovery.

PMID- 11244203
TI  - Recent progress in drug treatment for acute ischemic stroke.
AB  - The publication of the positive results of the National Institute of Neurological
      Disorders and Stroke (NINDS) trial of alteplase (a recombinant tissue plasminogen
      activator; rt-PA) for acute stroke patients in 1995 and its approval by the US
      Food and Drug Administration as well as the American Academy of Neurology and
      American Heart Association increased the interest and attention of the medical
      community in acute stroke treatment. However, the implication of this NINDS
      Stroke Study and other thrombolytic trials in clinical practice remains
      controversial and debated. Furthermore, the recent publication of the results
      from the European Cooperative Acute Stroke Study II (ECASS II) and Alteplase
      Thrombolysis of Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS)
      studies will feed the controversy, since the results of these two studies are
      disappointing and do not confirm the positive results of the NINDS Stroke Study
      as expected by clinicians managing patients with acute stroke. The Standard
      Treatment with Alteplase to Reverse Stroke (STARS) and Cleveland studies, which
      involved a large number of community hospitals to assess the safety profile and
      the benefit of rt-PA thrombolysis for acute stroke patients in clinical practice,
      have shown controversial results. Consequently, the issue arises of which is the
      more reasonable position concerning thrombolysis by alteplase, which seems to
      work but has not been proven yet beyond reasonable doubt? The recent publication
      of the results from the Prolyse in Acute Cerebral Thromboembolism (PROACT II)
      study has shown that intra-arterial thrombolysis with prourokinase is a benefit
      treatment in stroke patients with a proven middle cerebral artery occlusion
      within 6 h of stroke onset. Numerous trials devoted to neuroprotection against
      acute ischemic stroke have been prematurely stopped because of safety concerns or
      poor risk-benefit ratios, but some new neuroprotective drugs seem promising and
      are being tested in ongoing studies. The third issue under study concerns the use
      of antithrombotic drugs in the acute phase of stroke, particularly the new potent
      platelet glycoprotein IIb/IIIa antagonists such as abciximab. In this paper, we
      have reviewed selected recent clinical trials focusing on recent advances in
      acute stroke therapy.

PMID- 11244204
TI  - New challenges in the etiopathogenesis of atherothrombosis.
AB  - Atherosclerotic disease is a focal pathological event characterized by thickening
      and hardening of large arteries due to the accumulation of lipids, proteoglycans,
      blood and blood products, fibrous tissue and calcium deposits. The formation of
      arterial thrombi appears to be a significant factor for the occurrence of
      clinical acute complications in asymptomatic chronic atherosclerosis. The
      knowledge obtained on the mechanisms of platelet activation, signal transduction,
      receptor binding, zymogen activation and function, substrate recognition and
      adhesive events has been useful to design new intervention techniques with
      beneficial results and new highly promising strategies. It was initially thought
      that receptors were only involved in binding functions, but they have also been
      shown to be important factors in the transduction of information from the
      extracellular compartment to the inside of the cell, and that they partly control
      cell function, structure, proliferation and differentiation. The availability of
      monoclonal antibodies and the molecular biology techniques applied to the fields
      of thrombosis, and the interaction between blood cells and the vascular wall will
      provide tools to explore specific pathways of cell activation and interaction
      between cells. These studies, together with those aimed at finding the main
      agonists and substrates triggering and perpetuating an event, will be helpful to
      establish strategies for treatment and prevention of clinical events and to
      reduce the associated morbidity and mortality.

PMID- 11244205
TI  - Advantages of lipid-lowering therapy in cerebral ischemia: role of HMG-CoA
      reductase inhibitors.
AB  - Dyslipemia as a risk factor for ischemic stroke and indications for statins in
      the prevention of ischemic stroke are revised. The role of cholesterol levels as
      a risk factor for ischemic stroke is controversial. This could be due to failures
      in the design of early epidemiological studies. Recent studies, however, do
      suggest a clearer risk relationship between cholesterol levels and ischemic
      stroke. Studies conducted on the prevention of ischemic heart disease (IHD) with
      3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), using
      pravastatin and simvastatin, unequivocally show reductions in overall mortality,
      cardiovascular mortality, acute myocardial infarction and other coronary events.
      These studies show a reduction in the risk of ischemic stroke, and although
      relative risk reduction is great, absolute risk reduction is low; the reasons for
      this are analyzed. Apart from lipid mechanisms, statins act on the atheroma
      plaque; they have antithrombotic and possibly neuroprotecting properties. Statins
      reduce the number of strokes due to the decrease of atherothrombotic strokes,
      cardioembolic strokes secondary to IHD, and lacunar strokes related to
      atherothrombosis and probably to microatheromas. Although there are currently no
      specific studies available on the secondary prevention of stroke with statins,
      which are required to clarify certain points, according to European and American
      guidelines for prevention, statins would be indicated in the secondary prevention
      of atherothrombotic stroke, and in cardioembolic and lacunar stroke associated
      with clinical or silent atherosclerosis (IHD, peripheral artery disease).
      Patients with ischemic stroke of other etiologies, except for stroke in the young
      or other unusual causes, are patients with a high vascular risk (cardiac and
      cerebral) owing to the stroke itself, age and other vascular risk factors, and
      they should also be treated with statins, at least from the point of view of
      primary prevention of IHD. Natural statins (pravastatin and simvastatin) play an
      essential part in secondary prevention of ischemic stroke, together with
      antiaggregants, anticoagulants, angiotensin-converting enzyme inhibitors and the
      treatment of other vascular risk factors.

PMID- 11244206
TI  - Antiplatelet drugs: how to select them and possibilities of combined treatment.
AB  - Antiplatelets are the pivotal drugs in preventing recurrent stroke or other major
      vascular events in patients who have undergone TIA or stroke. Aspirin is the most
      widely used, although its effect is very modest (relative risk reduction 20%),
      and most physicians use between 100 and 325 mg daily as a maintenance dose. For
      patients who develop stroke on aspirin treatment, the options are either to
      increase the dose of aspirin or to administer another anti-aggregate. No study
      has yet been performed to support these approaches. In patients who cannot
      tolerate aspirin, the options are clopidogrel 75 mg once daily or dipyridamole
      400 mg combined with 50 mg aspirin. An approach which is very appealing, but not
      yet proven is to combine different antiplatelet drugs with different modes of
      action, such as aspirin and clopidogrel, in order to achieve a better and more
      effective antithrombotic effect. Further controlled trials are needed to justify
      this approach.

PMID- 11244207
TI  - A benefit/risk analysis of the prevention of brain ischaemia with anticoagulant
      drugs: when, how and whom to treat?
AB  - This paper summarises the benefits and risks of anticoagulant treatment in
      patients who have had cerebral ischaemia. In patients with a cardiac source of
      embolism (in most studies atrial fibrillation), anticoagulation with a target
      intensity of an INR of 2.0--3.0 is the therapy of first choice. In the case of a
      contraindication to such treatment, aspirin and ibuprofen are safe, but less
      effective alternatives. In patients with cerebral ischaemia of presumed arterial
      origin, anticoagulation with an achieved intensity of 3.0--4.5 proved not to be
      safe. Results from trials with more moderate anticoagulation regimes are awaited.

PMID- 11244208
TI  - Endarterectomy for carotid stenosis: new approaches in patient selection.
AB  - Results of randomized trials on carotid endarterectomy make it mandatory that
      therapeutic decisions for patients with carotid stenosis consider the degree of
      stenosis, presence of symptoms, skill of surgeon and time since the last ischemic
      event. Patients with severe (>70% by angiogram) stenosis should receive carotid
      endarterectomy, provided the operative risk is <6% and symptoms have recurred
      within 6 months. With moderate stenosis (50--69% by angiogram), and with similar
      low operative risk and time limit, males with hemispheric, nondisabling stroke
      and appropriate CT lesion will benefit from carotid endarterectomy. Patients with
      TIA only, retinal symptoms alone and who are women are not going to benefit in
      this range of stenosis. Particularly at risk with medical care alone are
      symptomatic patients with coexistent intracranial stenosis, widespread white
      matter lesions, intraluminal thrombi, contralateral occlusion and absence of good
      collateral circulation. The same high-risk patients, enjoy good long-term results
      from endarterectomy. Lacunar syndromes at presentation respond to endarterectomy,
      but with less benefit. Symptomatic patients do as well, regardless of age,
      provided patients with serious cardiac disorders and with organ failure are
      avoided. Serious doubt exists about indications for endarterectomy in
      asymptomatic subjects. Even if the upper limit of 3% perioperative risk is
      exceeded (and in large institutional databases and other studies, it usually is),
      the risk of large-artery strokes from the asymptomatic lesion is only slightly
      above the risk facing these subjects from lacunar and cardioembolic stroke. To
      prevent 1 large-artery stroke in 5 years in asymptomatic subjects requires that
      111 subjects be submitted to endarterectomy.

PMID- 11244209
TI  - Carotid angioplasty and stenting: are they therapeutic alternatives?
AB  - Clinical trials have shown that carotid surgery prevents stroke, but also has a
      significant risk of morbidity. Percutaneous transluminal angioplasty and stenting
      (endovascular treatment) can also be used to treat carotid stenosis and have the
      advantage of avoiding general anaesthesia, cranial nerve injury and the
      discomforts of surgery. However, there are several potential complications of
      endovascular treatment, including intimal dissection and plaque rupture, and the
      long-term consequences of restenosis. More embolic signals are detected during
      and immediately after carotid angioplasty than during carotid surgery, although a
      randomised comparison showed no difference in neuropsychological outcomes. The
      large published case series of carotid endovascular treatment suggest a similar
      major morbidity rate to surgery, but a small single centre randomised trial
      reported very poor results in stented patients. Trial data from the much larger
      Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS) has been
      more encouraging. Results are available from 504 patients with carotid stenosis
      randomised to surgery or endovascular treatment. Endovascular treatment was
      carried out by percutaneous transluminal angioplasty using balloon catheters with
      the adjunct use of stents in 22%. Audited safety analysis by intention to treat
      showed no difference in the outcome measure of disabling stroke or death within
      30 days of treatment, but the rate of treatment related death or stroke lasting
      more than seven days was relatively high in both groups (endovascular treatment
      10%, surgery 9.9%). Minor complications, particularly cranial nerve palsy and
      haematoma were significantly less frequent in the endovascular group, but
      restenosis was significantly more common. Both treatments appeared equally
      effective at preventing stroke recurrence with no difference in the rates of
      stroke during follow-up for up to 3 years. Techniques of carotid angioplasty and
      stenting improved over the course of CAVATAS, and new designs of stents, filters
      and protection devices are being developed. Further large, multicentre randomised
      trials are therefore being started which will evaluate primary stenting of
      carotid artery stenosis in patients with cerebrovascular disease. Until the
      results are available, it will remain uncertain whether angioplasty and stenting
      are safe and effective therapeutic alternatives to surgery.

PMID- 11244210
TI  - Mapping pathological (99m)Tc-d,l-hexamethylpropylene amine oxime uptake in
      Alzheimer's disease and frontal lobe dementia with SPECT.
AB  - Seventeen patients with probable Alzheimer's disease (AD), 7 patients with
      frontal lobe dementia (FLD) and 19 control subjects (NOR) were examined by
      (99m)Tc-d,l- hexamethylpropylene amine oxime ((99m)Tc-HMPAO) SPECT. Images were
      standardised in the same 3D space and averaged within each group. After
      normalisation, the three sets of images were analysed in all cerebral lobes,
      hippocampus, thalamus and basal ganglia. In AD, the (99m)Tc-HMPAO uptake values
      were significantly reduced, as compared to NOR, in the parietal, temporal and
      insular lobes. In patients with FLD, the uptake was altered in all lobes with the
      exception of the parietal lobe. The uptake in the nucleus caudatus decreased
      significantly in both AD and FLD as compared to NOR. The uptake in the anterior
      cingulate cortex was significantly reduced in FLD. Subtraction images highlighted
      all significantly decreased areas. In conclusion, standardising SPECT in a common
      space and subtracting data from a control group improves the visual
      interpretation of images. In this study, the typical temporo-parietal and fronto
      parietal (99m)Tc-HMPAO uptake reductions were found in AD and FLD, respectively.
      The uptake in the nucleus caudatus was found to decrease significantly in AD and
      FLD and the one in the anterior cingulate cortex was reduced in FLD.

PMID- 11244211
TI  - Mutations of the notch3 gene in non-caucasian patients with suspected CADASIL
      syndrome.
AB  - The Notch3 gene has been recently identified as a causative gene for cerebral
      autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
      (CADASIL). To investigate the genetic contribution of Notch mutations in familial
      cases with vascular leukoencephalopathy, we screened 13 patients from 11
      unrelated families, which were selected on the basis of magnetic resonance
      imaging findings and positive family history. We identified three different
      missense mutations in 5 patients from 4 families. Two (Arg90Cys and Arg133Cys)
      are the same as previously reported in Caucasian patients, the other (Cys174Phe)
      is a novel mutation causing a loss of a cysteine in epidermal-growth-factor-like
      repeats of Notch3. These data indicate that the CADASIL Notch3 mutations were
      found in approximately 35% of familial cases with leukoencephalopathy, suggesting
      genetic heterogeneity of the disease.

PMID- 11244212
TI  - Occipital glucose metabolism in dementia with lewy bodies with and without
      Parkinsonism: a study using positron emission tomography.
AB  - Reduction of glucose metabolism in the occipital lobe is reported in dementia
      with Lewy bodies (DLB) and Parkinson's disease. If dysfunction of the
      nigrostriatal system is responsible for occipital hypometabolism, (1) DLB
      patients with parkinsonism would show a lower occipital metabolism than do
      patients without parkinsonism, and (2) DLB patients without parkinsonism would
      show an occipital metabolism comparable to those of normal subjects and patients
      with Alzheimer's disease (AD). To examine these hypotheses, we studied the
      regional cerebral metabolic rate of glucose (rCMRglc) in patients with a clinical
      diagnosis of DLB or AD, using (18)F-fluorodeoxyglucose and positron emission
      tomography. The subjects consisted of 15 DLB patients with parkinsonism, 7 DLB
      patients without parkinsonism and 7 AD patients without parkinsonism. The medial
      and lateral occipital rCMRglc was significantly lower in the DLB patients without
      parkinsonism than in the AD patients. There were no significant differences in
      occipital metabolic rates between the DLB groups with and without parkinsonism.
      DLB patients without parkinsonism showed a significant reduction of occipital
      glucose metabolism which is comparable with that of DLB patients with
      parkinsonism. The neurobiological bases of occipital hypometabolism in DLB may be
      pathological processes in the brainstem or basal forebrain structures other than
      the nigrostriatal system.

PMID- 11244213
TI  - A comparison of medial and lateral temporal lobe atrophy in dementia with Lewy
      bodies and Alzheimer's disease: magnetic resonance imaging volumetric study.
AB  - OBJECTIVES: To compare medial and lateral temporal lobe atrophy on magnetic
      resonance imaging (MRI) in dementia with Lewy bodies (DLB) and Alzheimer's
      disease (AD), and to examine the relationship between volumetric indices and
      cognitive and non-cognitive symptoms. METHODS: T(1)-weighted 1.0-tesla MRI scans
      were acquired in elderly subjects with DLB (n = 26; mean age = 75.8 years) and AD
      (n = 22; 77.3 years) and normal controls (n = 26; 76.2 years). MRI-based volume
      measurements of the hippocampus, parahippocampus, fusiform gyrus, combined
      inferior and middle temporal gyri, and superior temporal gyrus were acquired.
      RESULTS: Hippocampal and parahippocampal volumes were significantly larger in
      subjects with DLB compared to AD. Differences in hippocampal volumes between DLB
      and AD were observed across the entire length, and in all subjects with dementia
      there was a loss of hippocampal asymmetry compared to normal controls. Atrophy of
      temporal lobe structures correlated with memory impairment in both groups, and
      with age in DLB. There was no association between atrophy and psychotic symptoms
      in either group. CONCLUSIONS: Subjects with DLB and AD have a different pattern
      of temporal lobe atrophy with the most striking differences relating to medial
      rather than lateral temporal lobe structures. These structural differences could
      explain the relative preservation of memory function in DLB compared to AD.

PMID- 11244214
TI  - Excess functional disability among demented subjects? Findings from the Canadian
      Study of Health and Aging.
AB  - Dementia has been recognized as the strongest determinant for developing
      functional disability. However, dementia patients typically present with
      concomitant illness, thereby making difficult a determination of the fraction of
      disability due to dementia. The objective of this study was to estimate the
      prevalence of functional disability among demented and nondemented people and to
      estimate the excess disability in demented subjects net of conditions
      independently associated with disability in older people, using data on nearly
      2,900 subjects from the clinical examination of the 1991 Canadian Study of Health
      and Aging. Unadjusted specific disability prevalence (in bathing, dressing,
      grooming, toileting and stool and urinary incontinence) is considerably greater
      among demented subjects than among cognitively normal or cognitively impaired but
      not demented subjects. After adjustments, specific disability in demented
      subjects is somewhat reduced in comparison to nondemented and cognitively
      impaired but not demented subjects. Thus, even when one considers the influence
      of a history of physical illnesses that typically result in disability, the link
      between disability and dementia is only marginally attenuated.

PMID- 11244215
TI  - Alzheimer's disease and the cerebellum: a morphologic study on neuronal and glial
      changes.
AB  - Structural manifestations of Alzheimer's disease (AD) including neuronal loss
      were investigated in 12 cases of AD and in 10 healthy age-matched controls, with
      focus on the cerebellum. Linear Purkinje cell (PC) density was measured in the
      vermis and cerebellar hemispheres. Neurons were also counted in the inferior
      olivary nucleus. In vermis of the AD cases, the mean PC number was significantly
      lower (p = 0.019) than in the controls. The neurons in the inferior olive were
      similarly fewer, though not significantly (p = 0.13). Molecular layer gliosis and
      atrophy in the vermis was clearly severer in AD than in the controls. Features
      typical of cerebral Alzheimer encephalopathy (plaques, tangles and
      microvacuolization) were inconspicious. The structural cerebellar changes in the
      AD cases were thus neuronal loss, atrophy and gliosis, judged to represent the
      disease process, and with a main involvement in the vermis. This may be reflected
      in some of the symptoms and signs seen in AD, signs that are generally overlooked
      or judged to be of noncerebellar origin.

PMID- 11244216
TI  - Synaptosomal proteins, beta-soluble N-ethylmaleimide-sensitive factor attachment
      protein (beta-SNAP), gamma-SNAP and synaptotagmin I in brain of patients with
      Down syndrome and Alzheimer's disease.
AB  - Although it is well-known that synaptosomal proteins are deranged in
      neurodegenerative disorders, no information is available at the protein-chemical
      level as mainly immunochemical or immunohistochemical data were reported
      previously. We therefore investigated synaptosomal proteins in brain specimens
      from patients with Down syndrome (DS) and Alzheimer's disease (AD) to challenge
      the DS synaptic pathology as well as the relevance of DS to AD in synaptic
      pathology. For the aim of this study, we employed two-dimensional electrophoresis
      and matrix-associated laser desorption ionization mass spectroscopy and
      determined beta-soluble N-ethylmaleimide-sensitive factor attachment protein
      (beta-SNAP), gamma-SNAP and synaptotagmin I (SYT I) in 7 individual brain regions
      of controls and patients with DS and AD. In DS brain, beta-SNAP was significantly
      reduced in temporal cortex (p < 0.01). SYT I (p65) and SYT I (pI 7.0) were
      significantly reduced in thalamus (p < 0.01 and p < 0.05, respectively). In AD
      brain, beta-SNAP was significantly decreased in temporal cortex (p < 0.05). SYT I
      (p65) was significantly reduced in cerebellum (p < 0.05), and temporal (p <
      0.001) and parietal cortex (p < 0.01). SYT I (pI 7.0) was significantly reduced
      in temporal (p < 0.001) and parietal cortex (p < 0.01) and thalamus (p < 0.01).
      gamma-SNAP did not show any change in both DS and AD. The findings may explain
      impaired synaptogenesis in DS and AD brain, which is well documented in DS brain
      already early in life, and/or synaptosomal loss secondary to neuronal loss
      observed in both neurodegenerative disorders. It may also represent, reflect or
      account for the impaired neuronal transmission in DS and AD, caused by
      deterioration of the exocytic machinery. Here, we provide evidence for several
      deranged synaptosomal proteins in several brain regions at the protein level
      indicating deficient synaptosomal wiring of the brain in DS and AD.

PMID- 11244217
TI  - Comparison of brain perfusion in corticobasal degeneration and Alzheimer's
      disease.
AB  - To compare brain perfusion between corticobasal degeneration (CBD) and
      Alzheimer's disease (AD), we measured regional cerebral blood flow (rCBF)
      semiquantitatively with single-photon emission computed tomography in 10 patients
      with CBD and 16 with AD. There was no significant difference in age or illness
      duration between the patients with CBD and AD. Mini-Mental State Examination
      scores were significantly lower in the AD patients than in the CBD patients. All
      CBD patients showed asymmetric akinetic-rigid syndrome and limb apraxia. Four CBD
      patients were demented, and 1 AD patient had parkinsonism. Compared with 12 age
      matched control subjects, the average of the left and right rCBF values for the
      CBD patients was significantly reduced in the prefrontal, anterior cingulate
      (AC), medial premotor, sensorimotor (SM), posterior parietal (PP) and superior
      temporal (ST) cortices as well as in the basal ganglia (BG) and thalamus (Th),
      while the prefrontal, PP and ST cortices were significantly hypoperfused in the
      AD patients. In the CBD patients, rCBF was significantly less in the AC and SM
      cortices, and in the Th and BG, and significantly greater in the PP cortex than
      in the AD patients. Interhemispheric differences of rCBF in the inferior
      prefrontal and SM cortices were significantly greater in the CBD patients than
      the AD patients. It is concluded that rCBF comparison may aid in differentiating
      CBD from AD.

PMID- 11244218
TI  - Interrater reliability of the modified Jadad quality scale for systematic reviews
      of Alzheimer's disease drug trials.
AB  - Drug therapies for Alzheimer's disease (AD) have been evaluated in clinical
      trials over the past 2 decades. Systematic reviews of AD drug trials can shed
      more light on the efficacy of pharmaceutical interventions. The modified Jadad
      scale can be used to assess the quality of trial reports that are candidates for
      inclusion in these systematic reviews. The interrater reliability of the modified
      Jadad scale was examined during such a review. Three blinded reviewers rated the
      quality of 42 AD drug trial reports: the intraclass correlation coefficient was
      0.90. The modified Jadad scale appears to be a useful tool for AD research
      because of the very good interrater reliability. Also, it is composed of items
      that are well suited to the specific disease characteristics of AD. Further
      research should focus on the validity of this instrument.

PMID- 11244219
TI  - Nevi and melanoma: lessons from Turner's syndrome.
AB  - Females with Turner's syndrome (TS) have a markedly increased number of cutaneous
      nevi. While this is a well-recognized risk factor for cutaneous melanoma (CM),
      the incidence of this tumor in TS and the implications for our understanding of
      nevi and melanoma have not previously been considered. Here we report a case of
      an anorectal melanoma in a woman with TS and a review of the literature. Overall,
      there appears to be a lower than expected incidence of CM. Possible explanations
      are discussed and in particular the possible relationship between sex hormones
      and melanoma development as these girls fail to undergo normal pubertal
      development. Further study of this syndrome may provide important insights into
      the genetic factors involved in normal melanocyte and nevus development, the
      potential influence of sex hormones on melanoma development and the relationship
      between the presence of nevi and the risk of developing CM.

PMID- 11244220
TI  - Atopic signs and symptoms: assessing the 'atopy score' concept.
AB  - BACKGROUND: Score concepts have been suggested for the standardised diagnosis of
      atopic dermatitis, incorporating various anamnestic and clinical minor criteria
      of atopy, including the 'Erlangen Score', developed in the hospital-based setting
      of a dermatitis clinic. OBJECTIVE: To evaluate the properties of this score in
      the context of a population-based epidemiological study. METHODS: The association
      between relevant atopic criteria and previous or current flexural eczema was
      evaluated in 2,352 hairdressing apprentices. RESULTS: The association was not as
      strong as in the patient-based studies, comparing the respective odds ratios.
      Accordingly, the discriminating power of the Erlangen Score was poor, resulting
      in low sensitivity (55.7%) and specificity (73.8%) for, e.g., 8 points as
      cutpoint. CONCLUSION: While the score appears useful to summarise minor criteria,
      the individual relevance of its point values should not be overestimated in view
      of a low positive predictive value in a population (compared to a clinical)
      setting.

PMID- 11244221
TI  - Analysis of p53, p21(Waf1/Cip1) and TGF-beta(3) immunohistochemical staining in
      Bowen's disease.
AB  - BACKGROUND: The p53 gene is one of a family of tumor suppressor genes that have
      been implicated in the genesis of a wide variety of malignant neoplasms including
      Bowen's disease. Its role in oncogenesis and tumor progression is thought to be
      of importance. Transforming growth factor beta (TGF-beta) is the most potent
      known inhibitor of the progression of normal epithelial cells through the cell
      cycle. p21(Waf1/Cip1) is thought to mediate p53 signaling induced by DNA-damaging
      agents to arrest the cell cycle. OBJECTIVE: The present study evaluates the
      expression of p53, p21(Waf1/Cip1) and TGF-beta(3) protein and speculates on their
      role in Bowen's disease. METHODS: Sixteen patients seen at our clinic between
      1993 and 2000 were examined. We analyzed p21(Waf1/Cip1), p53 and TGF-beta(3)
      immunohistochemical staining in all specimens. RESULTS: In 7 of the Bowen's
      disease patients, overexpression of p53-positive cells was present in the middle
      and basal layers, and intense staining of p21(Waf1/Cip1) was observed in the
      upper spinous layers. In the other 9 Bowen's disease patients, we found
      positively stained cells for p21(Waf1/Cip1) but negative p53 immunostaining in
      the upper epidermal layer. Downregulated TGF-beta(3) expression was detected in
      all layers except the upper spinous layers. CONCLUSION: These observations
      suggest different roles for p21(Waf1/Cip1) and p53 within abnormal cells in
      Bowen's disease. p21(Waf1/Cip1) may induce terminal differentiation to the
      superficial layer in Bowen's disease via either a p53-independent or -dependent
      pathway. Moreover, downregualtion of TGF-beta(3) immunostaining provides relevant
      information concerning the pathogenesis of Bowen's disease.

PMID- 11244222
TI  - Antidesmoglein autoantibodies in silicosis patients with no bullous diseases.
AB  - BACKGROUND: Pemphigus is an autoimmune bullous disease characterized by the
      presence of antidesmoglein autoantibodies. However, the mechanism of its
      autoantibody production remains unknown. In previous reports, we have described
      rare cases of pemphigus and pemphigoid associated with silicosis. It is well
      known that during long-term silicosis, some autoimmune diseases, such as systemic
      sclerosis, systemic lupus erythematosus or rheumatoid arthritis, can occur.
      OBJECTIVE: The aim of this study was to explore the presence of pemphigus or
      pemphigoid autoantibodies in silicosis patients without clinical bullous diseases
      or collagen diseases. METHOD: The presence of pemphigus antibodies was examined
      in 54 silicosis patients with no associated bullous diseases, using
      immunofluorescence, the enzyme-linked immunosorbent assay (ELISA) for desmoglein
      1 and 3, and immunoblotting methods. In the antibody-positive cases, HLA
      genotyping of peripheral lymphocytes was performed with PCR-RFLP. RESULTS: Seven
      out of the 54 patients were found to be positive for pemphigus antibodies and 1
      for bullous pemphigoid by immunofluorescence. In addition, by ELISA, 6 patients
      were found to be positive against the desmoglein 1 antigen, 2 against the
      desmoglein 3 antigen and 2 against both desmoglein 1 and desmoglein 3.
      CONCLUSION: The results of the present study strongly suggest the occurrence of
      pemphigus and pemphigoid autoantibodies in patients with silicosis. It remains
      unclear whether such patients will develop an autoimmune bullous disease in the
      future. Accordingly, long-term follow-up of antibody-positive patients is
      required.

PMID- 11244224
TI  - Sunscreen and risk of osteoporosis in the elderly: a two-year follow-up.
AB  - BACKGROUND: It has been suggested that the use of sunscreens to prevent skin
      cancer may put the population at risk of vitamin D deficiency, which in turn may
      lead to secondary hyperparathyroidism, loss of cortical bone and, ultimately,
      osteoporotic fractures. OBJECTIVE: To investigate whether sunscreen SPF15 may
      lead to loss of bone mass. METHODS: We followed 10 sunscreen users and 18
      controls over 2 years, including two summers, two winters and a basal period
      (winter). Bone mass was evaluated each season with dual x-ray absorptiometry.
      RESULTS: During follow-up, mild fluctuations in bone mass could be seen at Ward's
      site in both groups, without a definitive pattern. At the final visit, no
      significant loss of bone mass was observed in sunscreen users or in the control
      group. We did not observe any significant differences between groups throughout
      the study. CONCLUSION: Although the study samples in this work are small, and a
      slight variation in bone mass may not be detected, in a clinical setting,
      sunscreen SPF15 protection does not seem to increase the risk of osteoporosis.

PMID- 11244223
TI  - Protective effects of tanning on cutaneous DNA damage in situ.
AB  - BACKGROUND: The incidence of skin cancer, the most common type of cancer in the
      Western world, has been shown to be associated with the degree of exposure to
      solar radiation. However, little is known on how human skin can be protected
      against UV-induced DNA damage by constitutive and induced pigmentation.
      OBJECTIVE: To study the effect of skin pigmentation induced by a sunbed-type of
      treatment on the formation of UV-induced DNA damage in human skin in situ.
      METHODS: A photoproduct assay was performed in untanned and tanned skin of
      healthy volunteers. RESULTS: There is no significant difference in the induction
      of photoproducts between untanned and tanned skin. CONCLUSION: Our data
      demonstrate that constitutive skin pigmentation is more efficient than the
      induced one in protection against formation of photoproducts.

PMID- 11244225
TI  - The number and distribution of Merkel cells in rudimentary polydactyly.
AB  - BACKGROUND: Rudimentary polydactyly histologically reveals a marked neural
      proliferation in the dermis and a large number of Meissner corpuscles in the
      dermal papillae. OBJECTIVE: Our study was performed to determine whether this
      neural proliferation is related to Merkel cells. METHOD: Using an antibody to
      cytokeratin 20, we examined the number and distribution of Merkel cells in 5
      cases of rudimentary polydactyly, including an immature case without Meissner
      corpuscles. RESULTS: Only the case without Meissner corpuscles had a markedly
      large number of Merkel cells and some dermal Merkel cells. CONCLUSION: The normal
      number of Merkel cells in the mature cases suggests that abundant Merkel cells
      may appear at first and disappear after the development of neural proliferation.
      Merkel cells may be associated with the generation of cutaneous nerve plexus and
      nerve endings in the upper dermis, and possibly with the development of Meissner
      corpuscles, at the early stage of rudimentary polydactyly.

PMID- 11244226
TI  - Topical metronidazole in seborrheic dermatitis--a double-blind study.
AB  - OBJECTIVE: To evaluate the role of topical metronidazole gel in the treatment of
      seborrheic dermatitis. METHODS: Forty-four patients with seborrheic dermatitis
      were enrolled in the study. All topical treatments were stopped for at least 2
      weeks before the patients were allocated at random to receive either
      metronidazole 1% gel or placebo for 8 weeks. The severity score was measured at
      the initial evaluation, and the patients were followed up at 2-week intervals for
      8 weeks. A global evaluation of improvement was done at 8 weeks. RESULTS: Thirty
      eight patients completed the study; 21 patients in the metronidazole group and 17
      patients in the placebo group could be evaluated. There was a statistically
      significant decrease of the mean score even at week 2; the difference became
      highly significant at 8 weeks (p < 0.001). On the final evaluation at 8 weeks, 14
      patients in the metronidazole group showed marked improvement to complete
      clearance as compared to only 2 patients having moderate improvement in the
      placebo group (p < 0.001). CONCLUSION: The present trial has demonstrated the
      effectiveness of topical 1% metronidazole gel in seborrheic dermatitis.

PMID- 11244227
TI  - Pharmacoeconomic evaluation of calcipotriol (Daivonex/Dovonex) and UVB
      phototherapy in the treatment of psoriasis: a Markov model for The Netherlands.
AB  - BACKGROUND: The high prevalence and chronic nature of psoriasis leads to high
      costs in relation to the treatment and control of the disease. A number of
      clinical trials have shown that a combination therapy of calcipotriol cream
      (Daivonex/Dovonex), Leo Pharmaceutical Products) and ultraviolet B phototherapy
      (UVB) decreases the total number of UVB exposures required compared to UVB
      treatment alone. From a societal point of view, the addition of calcipotriol to
      UVB therapy could achieve cost savings due to the fewer UVB treatments needed and
      the reduced travelling and time off work for patients. Fewer UVB exposures may
      also have other beneficial effects, i.e., shortened waiting lists and less risk
      to patients of developing cancer or photoaging of the skin. OBJECTIVE: To compare
      the cost-effectiveness of treating psoriatic patients in the Netherlands with
      calcipotriol cream used daily combined with twice weekly UVB treatments to
      emollient used daily combined with UVB given 3 times weekly. METHODS: Based on
      the clinical results from a Canadian trial, a decision-analytical model was
      constructed to simulate treatment outcomes and estimate the costs of managing
      psoriatic patients in the Netherlands over a period of 20 weeks from initiation
      of therapy. Unit costs and details of standard treatment protocols were collected
      from Dutch dermatology centres in hospitals and the community for use in the
      model. Other therapies, such as topical corticosteroids, tar or dithranol were
      not investigated in this analysis. RESULTS: The total cost of managing psoriatic
      patients in the Netherlands over a 20-week period is estimated as EUR 1,175.90
      for those treated with calcipotriol and UVB and EUR 1,212.14 for patients treated
      with emollient and UVB. Thus, the former treatment, adding calcipotriol to UVB
      phototherapy, provides a minor cost saving of EUR 36.24 (3%) compared to the cost
      of UVB treatment alone. Sensitivity analyses demonstrated that these results are
      sensitive to changes in the cost of UVB treatment. CONCLUSION: Calcipotriol
      treatment combined with UVB phototherapy is a cost-neutral alternative to UVB
      phototherapy used with an emollient. The patients achieve treatment success in
      the same time on both treatments but the former, with calcipotriol, requires less
      exposure to UVB radiation. The additional drug costs from using calcipotriol are
      offset by savings from the fewer UVB sessions required. Essential beneficial
      effects for patients are less inconvenience, less risk of developing photoaging
      of the skin and less exposure to potentially carcinogenic radiations.

PMID- 11244228
TI  - Pentoxifylline attenuates UVB-induced cutaneous erythema.
AB  - BACKGROUND: The mechanism for ultraviolet-B (UVB)-associated cutaneous erythema
      may involve production of tumor necrosis factor alpha (TNF-alpha). Pentoxifylline
      inhibits TNF-alpha production. OBJECTIVE: To assess the effect of oral
      pentoxifylline on UVB-induced erythema in humans. METHODS: Baseline minimum
      erythema doses (MEDs) for UVB were measured. Subjects received pentoxifylline 400
      mg orally every 8 h for 4 doses. MED assays were repeated 2 h after the last dose
      of pentoxifylline. Pre- and posttreatment MED results were assessed by the paired
      t test. RESULTS: Oral administration of pentoxifylline to 7 normal adults
      elevated the MED for UVB in all 7 individuals. CONCLUSION: Pentoxifylline may
      diminish the cutaneous sunburn response to UVB radiation when it is administered
      prior to ultraviolet exposure.

PMID- 11244229
TI  - Microwave corneosurfametry and the short-duration dansyl chloride extraction test
      for rating concentrated irritant surfactants.
AB  - BACKGROUND: There are ethical concerns to conduct in vivo tests in the animal and
      human to provide evidence that cosmetics and other topical products are safe.
      OBJECTIVE: To compare two methods, namely the short-duration dansyl chloride
      extraction test and the microwave corneosurfametry bioassay, to test the
      irritation potential of concentrated surfactant systems. METHODS: Five
      surfactants and water were tested using the in vivo test and the bioassay.
      RESULTS: A significant linear correlation was found between data yielded by the
      two procedures. CONCLUSION: The short-duration dansyl chloride extraction test
      and the microwave corneosurfametry bioassay provide similar information. The
      latter has the advantage of being safe.

PMID- 11244230
TI  - Cutaneous plasmacytosis: an unusual presentation sharing features with POEMS
      syndrome?
AB  - Cutaneous plasmacytosis is a recently described skin disorder consisting of brown
      to red papules and nodules containing polyclonal plasmacytes. In this particular
      case, leg ulcers developed but also a diffuse patchy hyperpigmentation coexisting
      with a primary hypothyroidisim. The last two signs have only been described to
      date in POEMS syndrome, which is linked to monoclonal plasmacytic proliferation,
      and might suggest an overlap between these two entities.

PMID- 11244231
TI  - Cherry angiomas associated with exposure to bromides.
AB  - Cherry angiomas are the most common vascular proliferation; however, little is
      known about the pathogenesis and etiology of these lesions. We present two
      laboratory technicians who were exposed to brominated compounds for prolonged
      periods and who developed multiple cherry angiomas on the trunk and extremities.
      We suggest that the association between exposure to bromides and cherry angiomas
      should be investigated by a controlled study.

PMID- 11244232
TI  - Bullous pemphigoid in a patient treated with UVA-1 phototherapy for disseminated
      morphea.
AB  - Bullous pemphigoid is an autoimmune disease of the skin characterized by the
      production of antibodies directed at structures of the basement membrane zone
      (BMZ) leading to subepidermal blisters. Several causative triggers have been
      described in the literature, among them UV light. Here, we report on a 73-year
      old Caucasian female with disseminated morphea who developed blisters on her
      extremities after receiving whole-body UVA-1 phototherapy. The initial
      differential diagnosis of a phototoxic versus photoallergic reaction was ruled
      out as the lesions continued to spread after discontinuation of phototherapy.
      Histological and direct immunofluorescence examination showing a subepidermal
      blister and linear IgG deposits along the BMZ along with detection of circulating
      anti-BMZ antibodies led to the diagnosis of bullous pemphigoid. Immunosuppressive
      therapy resulted in regression of all blisters. After ruling out other possible
      causes, such as neoplasias or drugs, we conclude that UVA-1 has to be regarded as
      the most likely trigger of the disease.

PMID- 11244233
TI  - Non-Herlitz junctional epidermolysis bullosa without hair involvement associated
      with BP180 deficiency.
AB  - Junctional epidermolysis bullosa (JEB) is a clinically and genetically
      heterogeneous recessively inherited blistering disease of the skin and mucous
      membranes due to impaired epithelial adhesion. In particular, defective
      expression of the 180-kD bullous pemphigoid antigen (BP180) has been correlated
      to a non-lethal (non-Herlitz) form of JEB, generalized atrophic benign
      epidermolysis bullosa (GABEB), characterized by widespread skin blistering
      healing with atrophy and by atrophic alopecia with onset in childhood. We report
      the case of a 33-year-old man suffering from a generalized blistering skin
      disorder since birth. He also presented nail dystrophy and tooth abnormalities.
      Mucosal involvement was limited to gingival erosion. Alopecia was absent and
      body, axillary and pubic hair were normal. Immunofluorescence analysis showed a
      markedly reduced expression of BP180, electron microscopy studies evidenced
      hypoplastic hemidesmosomes and Northern blot analysis confirmed a striking
      decrease in the amount of BP180 mRNA. The clinical features of our patient
      confirm that BP180 deficiency usually results in a non-Herlitz JEB form. However,
      the degree of skin, mucous membranes and hair involvement appears more variable
      and less typical than originally described for GABEB.

PMID- 11244234
TI  - Antiepiligrin cicatricial pemphigoid with autoantibodies to the beta subunit of
      laminin 5 and associated with severe laryngeal involvement necessitating
      tracheostomy.
AB  - We report the case of a 67-year-old Korean woman with antiepiligrin cicatricial
      pemphigoid. The patient's serum immunoprecipitated polypeptides that comigrated
      with those identified in serum from a representative patient with antiepiligrin
      cicatricial pemphigoid, and was reactive with the laminin beta3-subunit on
      immunoblotting. She presented not only with cutaneous, oral and ocular, but also
      with laryngeal and esophageal involvement. Because the supraglottic stenosis was
      severe, she had to undergo tracheostomy to maintain airway patency.

PMID- 11244235
TI  - The successful treatment of prurigo pigmentosa with macrolide antibiotics.
AB  - Recent studies have demonstrated that macrolide antibiotics have anti
      inflammatory as well as antibacterial effects. Therefore, macrolide antibiotics
      have been successfully used to treat patients with various inflammatory diseases.
      We evaluated the effect of macrolide antibiotics in 4 patients with prurigo
      pigmentosa who were treated with either 400 mg of clarithromycin or 300 mg of
      roxythromycin daily. Eruption and pruritus disappeared within a week in all the
      patients while those symptoms were unresponsive to other drugs. Although the
      mechanism of this effect remains unclear in patients with prurigo pigmentosa,
      macrolide antibiotics can be considered as an alternative treatment for prurigo
      pigmentosa.

PMID- 11244236
TI  - Unusual annular erythema associated with myelodysplastic syndrome.
AB  - We report a case of unusual annular erythema associated with myelodysplastic
      syndrome (MDS). A 58-year-old male with MDS developed annular erythema on his
      back, scaly erythema on the dorsa of hands, and exudative erythema on his
      eyelids. Histological examination revealed a mononuclear cell infiltrate around
      vessels and follicles in the mid- to lower dermis. He had no history of treatment
      with granulocyte-colony-stimulating factor (G-CSF). Serum granulocyte-macrophage
      colony-stimulating factor (GM-CSF) level was slightly elevated (5.84 pg/ml,
      normal < 2.0 pg/ml), whereas other cytokines including G-CSF, IL-6, and IL-8 were
      within normal limits. Skin manifestations were much improved by systemic
      mepitiostane, and serum GM-CSF level returned to normal levels.

PMID- 11244237
TI  - An additional case of macular phylloid mosaicism.

PMID- 11244238
TI  - Extraordinarily large calcifying epithelioma without aggressive behavior.

PMID- 11244239
TI  - Love-bites on the forearm.

PMID- 11244240
TI  - Patients with epidermodysplasia verruciformis show no response to contact
      immunotherapy.

PMID- 11244241
TI  - Cutaneous cryptococcosis mimicking keloid.

PMID- 11244242
TI  - Erythema nodosum revealing oculoglandular tularemia.

PMID- 11244243
TI  - Frictional pyogenic granuloma of the nail bed.

PMID- 11244244
TI  - Lesions resembling polymorphic eruption of pregnancy several years after
      pregnancy.

PMID- 11244245
TI  - An odd case of abdominal purpura.

PMID- 11244246
TI  - Towards a novel treatment strategy for acute pancreatitis. 1. Reappraisal of the
      evidence on aetiogenesis.
AB  - Despite more than a century of research endeavour, there is no specific medical
      treatment for acute pancreatitis and early mortality is high - 20% of fatalities
      by the day after admission. I do not see any realistic prospect that today's
      focus on immunomodulation will provide a breakthrough either. The signs are that
      the outcome of acute pancreatitis is determined almost at its inception, and that
      those unfortunate individuals in whom the seeds for a precipitous course are sewn
      do not declare themselves until it is too late. This reappraisal of the evidence
      on disease aetiogenesis has been undertaken in an effort to fathom why this might
      be.

PMID- 11244247
TI  - Prostaglandin E inhibits indomethacin-induced gastric lesions through EP-1
      receptors.
AB  - BACKGROUNDS AND AIMS: We examined the effect of various prostaglandin E (PGE)
      analogs specific to EP receptor subtypes on indomethacin-induced gastric lesions
      in rats and investigated which EP receptor subtype is involved in the protective
      action of PGE(2) using EP-receptor knockout mice. METHODS: Gastric lesions were
      induced by subcutaneous administration of indomethacin (35 mg/kg). Gastric
      motility was measured using a balloon method, while neutrophil chemotaxis
      determined using a Boyden chamber. RESULTS: Indomethacin-induced gastric lesions
      were significantly prevented by PGE(2) as well as atropine, and the former effect
      was mimicked by sulprostone (EP(1)/EP(3)) and 17-phenyl PGE(2) (EP(1)) and
      antagonized by an EP(1) antagonist, ONO-AE-829. Neither butaprost (EP(2)), ONO-NT
      012 (EP(3)) nor 11-deoxy PGE(1) (EP(3)/EP(4)) showed any protection on the
      lesions. Indomethacin caused a marked increase in gastric motility; the response
      preceded the onset of lesions and was inhibited by atropine as well as PGE
      derivatives acting as EP(1) receptors. Neutrophil chemotaxis was inhibited by
      PGE(2), butaprost and slightly by 11-deoxy PGE(1), but not by either 17-phenyl
      PGE(2), ONO-NT-012 or atropine. In addition, indomethacin caused damage similarly
      in both wild-type and knockout mice lacking EP(1) or EP(3) receptors, yet the
      protective action of PGE(2) was observed in wild-type and EP(3) receptor knockout
      mice but totally disappeared in mice lacking EP(1) receptors. CONCLUSION: PGE(2)
      inhibits indomethacin-induced gastric lesions, through EP(1) receptors, and this
      effect may be functionally associated with inhibition of gastric motility but not
      of neutrophil activation/migration.

PMID- 11244248
TI  - Reversal of the gastric effects of nicotine by nitric oxide donor treatment.
AB  - Nicotine intensifies experimental gastric ulceration by reducing gastric mucosal
      blood flow (GMBF) and mucus. As both these parameters can be improved by nitric
      oxide (NO), we evaluated the impact of a NO donor in ethanol-induced gastric
      mucosal injury in rats administered nicotine. A nicotine solution or water was
      administered for 20 days to Sprague-Dawley rats. NO donor (isosorbide dinitrate)
      was given 60 and 10 min before preparation of ex vivo gastric chambers and
      exposure to ethanol. Chronic nicotine intake significantly reduced GMBF and
      gastric mucus content. Nicotine intensifies ethanol-induced gastric injury and
      short-term administration of NO donor failed to antagonize the ulcerogenic action
      from either nicotine or alcohol. In another study, rats drank nicotine solution
      for 20 days, after which the nicotine was withdrawn and replaced by water for 10
      additional days. NO donor was provided during these last 10 days. The gastric
      effects of nicotine persisted for at least 10 days after nicotine was withdrawn
      but then these effects could be abolished by prolonged NO treatment. Nicotine
      reduces plasma nitrite level, but gastric mucosal MPO activity remained
      unchanged. Our data suggest that nicotine cessation plus a longer period of NO
      donor administration can completely abolish the gastric effects of nicotine.

PMID- 11244249
TI  - Food-related gastrointestinal symptoms in the irritable bowel syndrome.
AB  - BACKGROUND/AIMS: Postprandial symptoms are common in patients with irritable
      bowel syndrome (IBS). However, existing studies have come to different
      conclusions about the role of food in the pathophysiology of IBS. We explored the
      prevalence of subjective food-related gastrointestinal (GI) symptoms and its
      relationship to clinical characteristics and psychological factors in IBS.
      METHODS: 330 patients with IBS and 80 healthy volunteers completed a food
      questionnaire developed for this study. The subjects graded their subjective
      symptoms after 35 different foods and a food score was obtained by adding the
      item scores. The relationship between subjective food-related GI symptoms and
      referral status, IBS subgroup (predominant bowel pattern), sex, anxiety,
      depression and body mass index (BMI) was estimated. RESULTS: In 209 (63%) of the
      patients the GI symptoms were related to meals. Gas problems and abdominal pain
      were the most frequently reported symptoms. Foods rich in carbohydrates, as well
      as fatty food, coffee, alcohol and hot spices were most frequently reported to
      cause symptoms. The food score was higher in patients than in controls (p <
      0.0001). In the IBS group higher scores were observed in patients with anxiety (p
      = 0.005), and females (p < 0.001), but the results were unrelated to IBS
      subgroup, referral status or BMI. The BMI did not differ between groups.
      CONCLUSION: A majority of IBS patients consider their symptoms to be related to
      meals. Especially foods rich in carbohydrates and fat cause problems.
      Nevertheless, the majority of IBS patients are normal or overweight. Female sex
      and anxiety predict a high degree of food-related symptoms in IBS.

PMID- 11244250
TI  - Effects of type-2 diabetes and troglitazone on the expression patterns of small
      intestinal sugar transporters and PPAR-gamma in the Zucker diabetic fatty rat.
AB  - BACKGROUND/AIMS: We have used the Zucker diabetic fatty (ZDF) rat to study the
      effects of type-2 diabetes and troglitazone on the small intestinal mucosal mass,
      sugar transporters and the peroxisomal proliferator-activated receptor, PPAR
      gamma. METHODS: Age-matched ZDF and lean control (ZLC) rats were fed a standard
      chow or a troglitazone-enriched diet for 6 weeks. The mucosa of the small
      intestines were then extracted, weighed, and SGLT1, GLUT2, GLUT5 and PPAR-gamma
      mRNA expression levels assessed by Northern blotting. In the same animal groups,
      Western blotting and immunohistochemistry were used to study SGLT1, GLUT2 and
      GLUT5 protein expression levels and targeting. RESULTS: The ZDF rat small
      intestinal mucosal mass was 60% greater than the ZLC rat. However, the expression
      levels of SGLT1, GLUT2, GLUT5 mRNA and protein, and PPAR-gamma mRNA in the ZDF
      and ZLC rats were the same. In addition, the targeting of brush-border GLUT5 and
      basolateral GLUT2 protein in the ZDF and ZLC rats were the same. Troglitazone
      treatment reduced SGLT1 mRNA and protein expression levels by 50% in ZDF and ZLC
      rats, but had no effect on mucosal mass or the expression levels of GLUT2 mRNA
      and protein, GLUT5 mRNA, and PPAR-gamma mRNA. The expression levels of GLUT5
      protein in troglitazone-treated ZLC rats were unchanged when compared to
      untreated ZLC rats. However, GLUT5 protein expression levels in the troglitazone
      treated ZDF rats were 50% below the untreated ZDF rats. CONCLUSIONS: Hyperphagia
      and insulin are the chronic regulators of small intestinal mucosal mass and sugar
      transporter expression patterns, respectively. Furthermore, troglitazone
      suppresses SGLT1 expression at the transcriptional level and GLUT5 at the post
      translational level, independent of changes in glycemia or PPAR-gamma gene
      expression.

PMID- 11244251
TI  - Oxygen metabolites in immune- stimulated ion transport in rat colon: modulation
      by taurine.
AB  - BACKGROUND/AIMS: Activation of cells within the lamina propria can cause
      electrogenic chloride secretion across intestinal epithelia by release and/or
      synthesis of mediator molecules, including reactive oxygen metabolites (ROMs). In
      this investigation we examined whether indirect (immune) stimulation of ion
      transport across rat colon was ROM-mediated. METHODS: Paired segments of rat
      colon, stripped of underlying smooth muscle, were mounted on Ussing chambers in
      order to measure electrogenic ion transport. Changes in short circuit current
      (SCC) were used as a measure of net electrogenic ion transport measured in
      response to the bacterial tri-peptide formyl-Met-Leu-Phe (fMLP) which was used to
      activate lamina propria neutrophils. The effect of the established anti-oxidants
      catalase and diethyldithiocarbamate (DDTC) and the putative anti-oxidant taurine
      upon immune-stimulated ion transport was examined. RESULTS: The anti-oxidant DDTC
      but not catalase significantly attenuated ion transport responses to fMLP.
      Taurine applied basolaterally reduced ion transport response to fMLP but not to
      the directly acting secretagogues forskolin. Taurine applied apically enhanced
      ion transport responses to fMLP. CONCLUSION: Anti-oxidants, including taurine,
      may be useful in treatment of colitis. The enhancement of effect seen when
      taurine was applied apically may have negative implications regarding the
      therapeutic usefulness of taurine administration to the lumenal compartment.

PMID- 11244252
TI  - High correlation between results of the [1-13C]-phenylalanine breath test and
      phenylalanine hydroxylase (EC 1.14.16.1) activity of the liver in rats.
AB  - BACKGROUND: (13)CO(2) is decreased in patients with end-stage liver disease by
      the [1-(13)C]-phenylalanine breath test. Decreased (13)CO(2) is supposed to be
      caused by the decreased ability of the liver to oxidize phenylalanine. However,
      no direct evidence has been reported. METHODS: The [1-(13)C]-phenylalanine breath
      test was performed in galactosamine hepatitis rats (n = 14) and control rats (n =
      8). Plasma phenylalanine concentration before intravenous administration of [1
      (13)C]-phenylalanine, the elimination rate of phenylalanine and the phenylalanine
      hydroxylase (PAH; EC 1.14.16.1) activity of the whole liver were examined.
      RESULTS: Increase of (13)CO(2) in the breath [Delta(13)CO(2) ( per thousand)] of
      galactosamine hepatitis rats 2 min after administration of [1-(13)C]
      phenylalanine was only 1/5 of that in control rats. The concentration of plasma
      phenylalanine and the elimination rate of plasma phenylalanine in hepatitis rats
      did not show significant differences compared to control rats. On the other hand,
      a clear difference in the activity of PAH was observed between hepatitis rats and
      control rats. Delta(13)CO(2) ( per thousand) 2 min after administration of [1
      (13)C]-phenylalanine was highly correlated to the PAH activity of the whole liver
      (r = 0.917). CONCLUSION: It was strongly indicated that decreased Delta(13)CO(2 )
      in hepatitis rats was the result of decreased activity of PAH.

PMID- 11244253
TI  - Severe life-threatening diarrhea caused by azathioprine but not by 6
      mercaptopurine.
AB  - Azathioprine and its active metabolite 6-mercaptopurine are of increasing
      importance in the treatment of chronic inflammatory bowel disease. Most of the
      toxicity and the side effects of the medications are well known. However, it is
      relatively unknown that azathioprine toxicity itself can produce devastating
      diarrhea in patients with inflammatory bowel disease. This leads to great
      difficulties in differential diagnosis. We describe 2 patients with severe
      intestinal toxicity. This was life-threatening in 1 patient after reintroducing
      the drug. We therefore believe that any rechallenge with azathioprine should be
      only undertaken in a controlled hospital environment when a reaction to
      azathioprine is suspected. In addition, we found that this devastating intestinal
      toxicity did not reoccur after rechallenge with its active metabolite 6
      mercaptopurine. Azathioprine and 6-mercaptopurine therefore cannot be used
      interchangeably.

PMID- 11244254
TI  - Modern management of rectal cancer.

PMID- 11244255
TI  - A modified technique of the Beger and Frey procedure in patients with chronic
      pancreatitis.
AB  - BACKGROUND: Resection of the pancreas requires control of tributaries of the
      superior mesenteric vein (SMV) inferior to the head of the pancreas as well as
      separation of the posterior surface of the pancreas from the SMV and from
      eventually existing collateral veins. This usually is the most tedious part when
      performing a resection of the pancreatic head, in particular if there are signs
      of portal hypertension. Portal vein pathology contributes to intra- and
      postoperative morbidity in pancreatic surgery. OPERATIVE TECHNIQUE: Instead of
      dissecting the pancreas along the anterior surface of the SMV our proposed
      technique allows resection of the head of the pancreas without division of the
      gland. This approach combines elements of Beger's duodenum-preserving pancreatic
      head resection and of Frey's limited local pancreatic head excision combined with
      a longitudinal pancreaticojejunostomy. This modified technique avoids the risk of
      a bleeding complication which is increased in the presence of portal hypertension
      and dilation. SUMMARY: The advantages of this modified technique over standard
      Beger and Frey procedures are: (1) the minimized risk of a bleeding complication
      in case of portal hypertension because pancreatic transsection does not need to
      be done, and (2) the considerably more radical excision as compared to local
      excision. Also, it represents the most minimal surgical trauma for resecting the
      head of the pancreas as compared to other commonly used techniques.

PMID- 11244256
TI  - Virologic and biochemical changes and prognosis after liver resection for
      hepatitis B virus-related hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: During the natural course of hepatitis B virus (HBV) infection,
      clearance of HB e antigen (HBeAg) and HB surface antigen (HBsAg) occurs with
      remission of liver disease. We investigated the effects of postoperative changes
      in virologic and biochemical parameters on the prognosis after liver resection
      for HBV-related hepatocellular carcinoma (HCC). METHODS: We investigated the
      relationship between postoperative changes in virologic and biochemical
      parameters and the incidence of intrahepatic recurrence and the outcome during a
      3-year period following surgery in 30 HCC patients with HBsAg. RESULTS: The
      incidence of intrahepatic recurrence of HCC was significantly higher in patients
      with acute postoperative exacerbation of hepatitis (p = 0.0084), a sustained high
      serum concentration of HBV DNA (> or = 5.0 mEq/ml, p = 0.001), and sustained
      expression of HBsAg after surgery (p = 0.0421). A high serum concentration of HBV
      DNA was significantly associated with a shorter survival time (p = 0.0447) and
      the cause of death was recurrence of HCC. CONCLUSION: Patients with acute
      postoperative exacerbation of hepatitis, sustained HBsAg expression, and
      sustained high serum concentrations of HBV DNA after surgery may require more
      intensive postoperative monitoring for HCC recurrence.

PMID- 11244257
TI  - Increased duodenal mucosa infiltration by mast cells in rats with portal
      hypertension.
AB  - BACKGROUND: Enteropathy characterized by vascular and inflammatory alterations in
      the submucosa and mucosa has been described in patients with portal hypertension.
      AIMS: To verify the theory of inflammatory etiopathogenesis in experimental
      portal hypertensive duodenopathy, a prehepatic portal hypertension model based on
      the development of a single and triple partial ligation of the portal vein was
      used in the rat. METHODS: Five rats in each group (male Wistar, 230-255 g) were
      subjected to single (group II) or triple (group III) partial ligation of the
      portal vein and then compared to 5 control animals (group I, no operation). The
      animals were sacrificed 6 weeks later to analyze the histological parameters of
      the duodenal mucosa and submucosa, i.e., number, diameter and area of submucosal
      vessels, density of mast cells and mitotic cells. Body, liver and spleen weights
      and collateral circulation type were also assayed. RESULTS: As was demonstrated
      by the collateral circulation in all of the animals, the partial portal ligation
      was successful. Compared to the controls, the number of vessels per microscopic
      field (25 +/- 3.16 vs. 18.60 +/- 1.52), their diameter (20.09 +/- 2.90 vs. 12.61
      +/- 3.97 microm, p < 0.05) and consequently their total area (12,749.30 +/-
      2,298.26 vs. 3,455.82 +/- 1,702.33 microm2) were increased in the animals with a
      single partial ligation (group II) as well as in animals receiving triple partial
      ligation (group III) (33 +/- 12.88, p < 0.05; 22.92 +/- 6.72 microm, p < 0.05 and
      51,376.95 +/- 43,732.24 miccrom2, p < 0.05, respectively). In addition, the
      density of mast cells increased from 3.26 +/- 1.18 in controls to 10.74 +/- 1.47,
      p < 0.01 and 22.50 +/- 6.42, p < 0.01 in single and triple partial portal ligated
      animals, respectively. Mitosis was significantly induced in crypts of the
      duodenal mucosa of the single portal ligated animals (25.20 +/- 1.78 vs. 17.40 +/
      1.14, p < 0.01) but was inhibited in triple partial ligated animals (12.40 +/-
      5.12, p < 0.05). Compared to controls, both groups of rats developed liver
      atrophy with a greater decrease in the liver/body weight ratio in the single
      (2.71 +/- 0.50%, p < 0.01) compared to the triple partial ligated animals (3.33
      +/- 0.09%, p < 0.01). CONCLUSIONS: The correlation of the degree of portal
      hypertension with the vascular changes and mast cell density suggests that both
      the hypertensive state and inflammation may play a role in the development of
      portal hypertensive intestinal vasculopathy. The inverse relation of portal
      hypertension with liver atrophy and mitosis rate in the crypts of the duodenal
      mucosa has not been clarified and should be investigated in future studies.

PMID- 11244258
TI  - Improved survival in small pancreatic cancer.
AB  - BACKGROUND: Although the incidence of pancreatic cancer is relatively low
      compared with other tumors (2.4%), the death rate is high. Tumor detection and
      treatment at an early stage is necessary to improve the poor prognosis of
      patients, as is demonstrated by some reports showing a 5-year survival rate
      varying between 19 and 41% for patients undergoing radical pancreatectomy with
      the highest survival in patients with small tumors. METHODS: In our study we
      retrospectively reviewed the histologic and demographic data of 596 patients who
      were admitted to the surgical units of the Careggi Hospital (University of
      Florence-AOC of Florence) between 1988 and 1994 with the incoming diagnosis of
      pancreatic cancer. RESULTS: Results are reported as the mean +/- standard
      deviation. The postoperative survival rate was calculated by the Kaplan-Meier
      method and statistical analysis was performed by the log rank test (significance
      p < 0.05). 247 patients had surgery, 110 with a curative intent. Postoperative
      mortality was 5.45%. The crude 5-year survival rate for patients who underwent
      curative surgery was 16.36% (18 patients), but for patients with small lesions
      confined to the pancreas (T1N0M0, 29 patients) this was even 31.03% (9 patients;
      p < 0.01, chi2 test). CONCLUSIONS: Our results indicate that it seems reasonable
      to consider these cancers as 'small', with survival reported in literature from
      35 to 41%, so they probably represent the only curable condition at the present
      time.

PMID- 11244259
TI  - Lactobacillus plantarum reduces infection of pancreatic necrosis in experimental
      acute pancreatitis.
AB  - BACKGROUND: Infection is the commonest cause of death in acute pancreatitis.
      Early reduction of commensal flora (particularly Lactobacillus species) and, at
      the same time, overgrowth of Enterobacteriaceae, especially Escherichia coli,
      have recently been described during acute pancreatitis. Lactobacillus plantarum
      has been shown to be effective in reducing the egress of endotoxin and microbial
      translocation in several experimental models such as chemically induced hepatitis
      and ulcerative colitis. AIM: The aim of the study was to determine whether L.
      plantarum 299v (Lp 299v) is capable of effectively reducing microbial
      translocation in experimental pancreatitis. METHODS: Acute pancreatitis was
      induced by isolation and ligation of the biliopancreatic duct in Lewis rats
      weighing 250-350 g. The animals were divided into 3 groups: group A, sham
      operation; group B, induction of pancreatitis and no further treatment, and group
      C, induction of pancreatitis + daily administration by gavage of a 5-ml/day
      suspension of Lp 299v at 0.5-1.0 x 10(9) bacteria/ml for 8 days, 4 days before
      and 4 days after induction of pancreatitis. All animals were sacrificed after 96
      h. Histological studies and microbiological analyses were performed. RESULTS: At
      sacrifice, 40/55 animals showed signs of severe pancreatitis. Since acute
      pancreatitis was the specific disease investigated, only these animals were
      subjected to further study. In group B, we found pathogenic micro-organisms in
      the mesenteric lymph nodes in 14/20 animals and in the pancreatic tissue in
      10/20. The bacterial flora consisted predominantly of E. coli, Enterococcus
      faecalis, Pseudomonas and Proteus species. In contrast, when the animals were
      kept under an 'umbrella' of Lp 299v, growth of E. faecalis or E. coli were
      detected only in 4/20 mesenteric lymph node cultures and in 3/20 pancreatic
      tissue cultures. CONCLUSIONS: Lp 299v is effective in reducing microbial
      translocation in experimental pancreatitis. Treatment with probiotic bacteria
      seems to be a promising alternative to antibiotic therapy.

PMID- 11244260
TI  - Characteristics and evolution of extraintestinal manifestations associated with
      ulcerative colitis after proctocolectomy.
AB  - AIMS: Describe the characteristics of extraintestinal manifestations complicating
      ulcerative colitis present preoperatively and determine their evolution after
      surgery. METHODS: Between 1976 and 1986, 281 patients with ulcerative colitis
      exhibiting one or more extraintestinal manifestations (EIM) before either IPAA (n
      = 147), Brooke ileostomy (n = 71), Kock pouch (n = 48) or ileorectostomy (n = 15)
      were assessed retrospectively. The clinical evolution of each manifestation was
      classified as having disappeared, improved, remained unchanged or aggravated
      postoperatively. An efficacy index was designed to assess the ratio of the number
      of cases cured or improved over the number of cases unchanged or aggravated. The
      relationship between EIM and gender, age, duration of disease and the type of
      surgery was also ascertained. RESULTS: 433 EIM were observed in 281 patients. The
      most common were arthralgias of the large joints (n = 146), of the sacroiliac
      joint (n = 59) and the small joints (n = 51). In comparison to patients without
      EIM having received the same operation during the same period of time, EIM were
      seen more often in women, younger patients, than those with longer duration of
      disease and the ileoanal anastomosis group. 60% had only one EIM at a time. Based
      on the efficacy index, thromboembolic accidents and erythema nodosum were the
      most commonly cured or improved. Ocular manifestations and primary sclerosing
      cholangitis were unaffected. The other EIM responded favorably but variably with
      improvement in two thirds of patients. The presence of a rectal remnant (IRA) or
      ileal reservoir did not affect the evolution of the EIM. CONCLUSIONS:
      Thromboembolic complications which are life-threatening, erythema nodosum and
      arthralgia of the small and large joints which impair quality of life, benefited
      the most from proctocolectomy. Those conditions may be considered preoperatively
      when making the decision for surgery.

PMID- 11244261
TI  - How effective is extensive nonsurgical treatment of patients with clinically
      active Crohn's disease of the terminal ileum in preventing surgery?
AB  - BACKGROUND/AIMS: The purpose of this study is to determine the effectiveness of
      extensive nonsurgical management of patients with clinically active Crohn's
      disease of the terminal ileum and to identify parameters that could predict
      failure of this nonsurgical approach. METHODS: All consecutive patients
      hospitalized for the first time because of active Crohn's disease of the terminal
      ileum between 1985 and 1994 were included. Two groups of patients were defined.
      Patients who responded favorably to the extensive treatment protocol (group I),
      and patients in whom an ileocolic resection had been performed (group II).
      Treatment and patient characteristics were related to outcome. RESULTS: Twenty
      nine (38%) of the 76 patients were treated successfully by nonsurgical management
      (group I) and did not have surgery until the end of follow-up (mean 8.0 years,
      range 3-12 years). In total, 47 patients (62%) had ileocolic resection (group
      II). Logistic regression analysis revealed that a longer time between onset and
      exacerbation of this disease, the presence of stenosis and extraintestinal
      manifestations were independent predictors of failure of nonsurgical treatment.
      CONCLUSION: Prolonged medical treatment is effective in only one third of the
      clinically admitted patients. It should be applied with caution particularly in
      patients exhibiting stenosis, extraintestinal manifestations or a known history
      of Crohn's disease of more than 5 years.

PMID- 11244262
TI  - Stability in incidence of acute appendicitis. A population-based longitudinal
      study.
AB  - BACKGROUND/AIM OF THE STUDY: During the past 50 years, a decrease in incidence of
      appendicitis has been reported. The various studies were retrospective and based
      on different data sources. In the present study, we analyze prospectively the
      incidence of acute appendicitis during a 10-year period in a well defined
      population of 265,000. METHODS: Prospective registration of all operations
      performed in patients with suspected acute appendicitis in the catchment area of
      a single institution. The diagnosis of acute appendicitis was based on histology
      in all cases. The annual incidence of acute appendicitis was calculated with
      regard to nonperforated and perforated acute appendicitis. MAIN RESULTS: Between
      1989 and 1998, 2,861 patients underwent surgery for suspected acute appendicitis.
      In 2,232 (78%) patients, acute appendicitis was confirmed histologically. Mean
      annual incidence was 84/100,000 (95% confidence interval 80 to 88/100,000). Crude
      incidence remained stable during the study period, with the exception of a
      significant increase in 1991 followed by a significant decrease the next year.
      Nonperforated acute appendicitis showed a different incidence pattern as compared
      to perforated acute appendicitis. CONCLUSION: In our prospective study, the
      incidence of acute appendicitis remained stable in our well-defined study
      population during the study period of 10 years. This is in contrast to the
      majority of studies during the last decades.

PMID- 11244263
TI  - Ileal neobladder for urinary bladder replacement following total pelvic
      exenteration for rectal carcinoma.
AB  - OBJECTIVE: The aim of this study was to determine the feasibility of using the
      ileal neobladder as a substitute for the urinary bladder following total pelvic
      exenteration for rectal carcinoma. PATIENTS AND METHODS: Between 1992 and 1998,
      we performed total pelvic exenteration with ileal neobladder in 5 men with rectal
      carcinoma. Four patients had primary tumors, and one had recurrent disease after
      low anterior resection for rectal carcinoma. Histological types were
      adenocarcinoma in 4 and squamous cell carcinoma in 1. Invaded organs were: the
      urinary bladder in 1, the urinary bladder and prostate in 2, the prostate and
      seminal vesicle in 1, and the prostate in 1. RESULTS: There was no operative
      death. In 1 patient, an ileal conduit was needed because of partial necrosis of
      the neobladder. Minor leakage on the dorsal wall of the neobladder occurred in 2
      patients, which was successfully stopped with simple closure and a gluteus
      maximus fasciocutaneous flap, respectively. All except one patient with the ileal
      conduit could void via the urethra. Complete daytime urinary continence was
      achieved, but nocturnal continence was maintained with voiding once or twice per
      night. As the urodynamic state, the mean maximum flow rate was 20.9 ml/s (range
      9.0-34.1), the mean average flow rate was 7.7 ml/s (range 3.0-11.0), and the mean
      voided volume was 285.5 ml (range 160-432). The mean length of follow-up was 47.8
      months. One patient died of local recurrence 38 months postoperatively, and 1
      died of pneumonia 10 months postoperatively. Both patients could void via the
      urethra until death. The other three patients are currently alive without any
      evidence of recurrence. CONCLUSIONS: Although total pelvic exenteration is a
      laborious surgical procedure, an ileal neobladder could be a good alternative to
      the urinary bladder enabling the patients to void via the urethra with urinary
      continence.

PMID- 11244264
TI  - Dehiscence of gastrojejunal stapled anastomosis after lithotripsy for
      nephrolithiasis.
AB  - We report the case of a 76-year-old woman with previous bariatric surgery and a
      large renal calculus following a prolonged lithotripsy session. The patient
      presented with peritonitis due to dehiscence of the gastrojejunal stapled
      anastomosis.

PMID- 11244265
TI  - Resection of spleno-renal shunt resulting in enhanced liver volume in a patient
      with congenital portosystemic shunt concomitant with early gastric cancer. Review
      of Japanese cases.
AB  - A 73-year-old man recurring hepatic encephalopathy due to a congenital
      splenorenal shunt concomitant with early gastric cancer was successfully treated
      by surgical intervention. The portal pressures before and after the shunt
      resection were 13.5 and 18 cm H2O, respectively. The liver was slightly atrophic
      and the histological specimen showed slight fibrosis and mild infiltration of
      lymphocytes in the portal area. After the operation, the encephalopathy was
      improved and the several factors of liver function also recovered. Interestingly,
      the liver volume estimated by abdominal CT clearly increased 1 month after the
      shunt resection. The encephalopathy in congenital portosystemic shunt might
      result from chronic liver ischemia and atrophy. Moreover, the shunt resection may
      enlarge the functional liver volume by increasing the portal blood flow.

PMID- 11244266
TI  - Pancreatoblastoma: ultrastructural and image DNA cytometric analysis.
AB  - BACKGROUND: Since the first description of a pancreatoblastoma as a malignant
      pancreatic tumour of childhood in 1957, approximately 60 cases have been
      reported. We present the symptoms, pathology, and therapy of this rare tumour in
      a 17-year-old girl. CASE REPORT: The patient initially presented with upper
      gastro-intestinal bleeding. During laparotomy a 16-cm (diameter) tumour was
      recognized in the pancreatic tail. Open biopsy and radical resection, followed by
      histological and immunohistochemical examinations, confirmed the diagnosis of a
      pancreatoblastoma. The results of single-cell DNA cytometry underlined the low
      DNA grade of malignancy of the primary tumour. In spite of adjuvant chemotherapy
      with cisplatin and adriamycin, the patient returned 22 months later with many
      hepatic and peritoneal metastases measuring up to 5 cm in diameter. Peritoneal
      tumour debulking and an extended hemihepatectomy were performed as a palliative
      treatment. Unfortunately, the patient died 18 months later from further tumour
      progression. CONCLUSIONS: A review of the literature reveals that a
      pancreatoblastoma in childhood has to be considered malignant, but usually shows
      a favourable prognosis in contrast to pancreatic neoplasms in adult patients. The
      treatment of choice is radical resection. Adjuvant chemotherapy or radiotherapy
      should be considered because of the metastatic potential of the tumour.

PMID- 11244267
TI  - Treatment of acute ischemic stroke: selecting the right treatment for the right
      patient.
AB  - At present, thrombolytic therapy is the only therapy approved for the treatment
      of acute brain injury among patients with ischemic stroke. While recombinant
      tissue plasminogen activator (rt-PA) is efficacious, its usefulness is limited,
      largely because of the very limited time window for its administration. Other
      medications that have potential neuroprotective actions or that affect
      coagulation or flow have not been established as efficacious or have not been
      approved by regulatory authorities. Additional therapies are needed to reduce the
      neurological consequences of ischemic stroke. Although the number of options to
      treat the stroke itself is limited, physicians should remember that management is
      multifaceted. Even if a patient cannot be treated with rt-PA, there is much that
      can be done to improve outcomes. Therapies of proven value are available to
      prevent or control complications, to augment recovery and to forestall recurrent
      stroke. The choice of treatment will continue to be made on a case-by-case basis
      and will be influenced by a number of variables. The most important factors are
      the time interval from stroke, the severity of the neurological impairments, the
      results of the baseline brain imaging and the cause of stroke.

PMID- 11244268
TI  - Restless legs syndrome: a clinical study of 55 patients.
AB  - BACKGROUND: Restless legs syndrome (RLS) is a common sleep disorder. In 1995,
      clinical criteria for the diagnosis of RLS were defined. OBJECTIVE: To describe
      the clinical spectrum in a series of unselected RLS patients meeting the new
      diagnostic criteria. METHODS: We prospectively assessed by questionnaire and
      clinical assessment the characteristics of 55 consecutive RLS patients (35 women,
      20 men; mean age = 62 +/- 16 years). RESULTS: In 27% of the patients, RLS started
      before the age of 20 years (early-onset RLS). Sensory disturbances were painful
      in 56% of patients and felt in legs (98%), arms (35%), and 'internally' (45%).
      Motor disturbances included 'dyskinesias while awake' (36%). Insomnia (58%) was
      commoner than hypersomnia (24%). In 67% of the patients, no etiology of RLS was
      found (idiopathic RLS). Early-onset RLS was more commonly familial (p = 0.01) and
      associated with 'growing pains' (p = 0.005) than late-onset RLS. Patients with
      RLS and hypersomnia were younger (p = 0.01) and less commonly had painful
      sensations (p = 0.04) than patients with RLS and insomnia. Patients with
      idiopathic RLS were younger (p = 0.004), and less commonly had insomnia (p =
      0.01) than patients with symptomatic RLS. CONCLUSIONS: RLS is a clinically
      pleomorphic syndrome, reflecting the contribution of multiple genetic and
      acquired factors in the pathogenesis of RLS.

PMID- 11244269
TI  - Aberrant pyramidal tract in the medial lemniscus of the human brainstem: normal
      distribution and pathological changes.
AB  - We examined the consistency of the so-called aberrant pyramidal tract (APT) in
      150 consecutive autopsied human brains using the modified Bielschowsky stain for
      axons. We were able to identify the APT in all brains except for one with
      holoprosencephaly. The APT left the pyramidal tract within the crus cerebri and
      passed in the medial lemniscus of the pons through the upper medulla oblongata.
      In 13 of the 63 brains with cerebrovascular diseases, wallerian degeneration was
      found in the APT on the ipsilateral side of the cerebral lesions. Further, the
      APT showed depletion of small-sized fibers in 2 of the 5 brains with multiple
      system atrophy. These findings confirmed that the APT is a normal descending
      fiber tract and a part of the pyramidal tract.

PMID- 11244270
TI  - Appearance of new lesions in two nonfamilial cerebral cavernoma patients.
AB  - Cavernomas are vascular malformations mostly observed in the central nervous
      system. They occur in sporadic and familial forms. Familial forms are
      characterized by the presence of multiple lesions, an autosomal dominant pattern
      of inheritance and possible de novo lesions. We report two sporadic cases whose
      follow-up showed the appearance of new lesions.

PMID- 11244272
TI  - Effects of moderate and high doses of alcohol on carotid atherogenesis.
AB  - The role of alcohol consumption on pathophysiology of atherosclerosis is not
      completely well established. Past studies were conducted with different
      methodological approaches, sometimes leading to opposing conclusions. The aim of
      this study was to determine the weight of alcohol intake on carotid
      atherosclerosis in a group of subjects asymptomatic for cardio-cerebrovascular
      diseases. They were examined by ultrasonographic assessment during the period
      1993 through 1997. Common risk factors of atherosclerosis and drinking habit were
      assessed by a standardized questionnaire. In this survey we confirm the J-shaped
      relationship between atherosclerosis and alcohol consumption. The effect of
      alcohol intake is more evident if we consider the presence of multiple internal
      carotid stenosis, or those greater than 25%, as outcome variables. These effects
      are independent from the other risk factors included in logistic regression
      paradigms (age, arterial hypertension, dyslipidemia, diabetes mellitus, family
      history of cardio-cerebrovascular disease, smoking and social status). Our study
      supported that a high level of alcohol intake plays a role as an independent
      factor in carotid atherogenesis.

PMID- 11244271
TI  - Incidence and predictive factors of cerebrovascular events in 8,846 elderly
      treated hypertensive patients during a 3-year follow-up: the PRESAGE study.
AB  - This epidemiological study was carried out as a 3-year follow-up project to
      assess the incidence of transient ischemic attacks (TIAs) and strokes; 8,846
      treated hypertensive patients (mean BP, 149/84 mm Hg) aged 65 years or over (mean
      age, 73.7 +/- 6.3 years), devoid of symptoms of dementia and with documented
      vascular risk factors were recruited from January 1994 to August 1995, by 1,598
      general practitioners in connection with 36 referral university neurology units
      throughout metropolitan France. Among these patients, 506 (5.7%) had at least one
      cerebrovascular event during the follow-up period: 309 (3.5%) experienced one or
      more isolated TIAs, and 197 (2.2%) had a stroke with or without a preceding TIA.
      A total of 510 TIAs were reported. The stroke subtypes were ischemia, hemorrhage,
      and unclassified in 70, 16, and 15% of the cases, respectively. The estimated
      annual stroke incidence was 7.42 per thousand. Of the 197 patients who developed
      strokes, 51 (26%) died. This case-fatality rate should be compared with the 4.5%
      mortality rate observed in the whole population during the study period. The 3
      subgroups (with isolated TIAs, strokes, or no events during the study) were found
      to differ regarding age, sedentary lifestyle, past history of cardiovascular
      events, duration of hypertension, and evidence of complicated hypertension
      (univariate analysis). The factors identified as predictive of a stroke
      (multivariate analysis) were: the patient's age; sedentary lifestyle; pulse
      pressure (SBP-DBP); identification of TIA at baseline, and presence of
      arrhythmias.

PMID- 11244273
TI  - Usefulness of primitive reflexes in demented and non-demented cerebrovascular
      patients in daily clinical practice.
AB  - The aim of this study was to investigate the usefulness of primitive reflexes
      (PRs) as additional alert signs in a routine clinical setting of cognitive
      decline in an elderly population of chronic ischemic cerebrovascular patients. We
      considered the occurrence of grasp, palmomental, glabellar and snout reflexes in
      75 demented (VaD) and 75 non-demented (VaND) patients, and in 75 healthy elderly
      controls. We never elicited more than two PRs in controls. The occurrence of
      three or four PRs provided the strongest correlation with dementia (p < 0.0001),
      with 93% specificity irrespective of low sensitivity. In conclusion, the
      occurrence of more than two PRs might serve as an additional warning sign of
      possible mild cognitive impairment in chronic ischemic cerebrovascular patients.

PMID- 11244274
TI  - Efficacy and tolerability of entacapone as adjunctive therapy to levodopa in
      patients with Parkinson's disease and end-of-dose deterioration in daily medical
      practice: an open, multicenter study.
AB  - Entacapone is a potent, reversible and orally active inhibitor of catechol-O
      methyltransferase. This open multicenter study evaluated the efficacy, safety and
      tolerability of entacapone as adjunct therapy to levodopa/dopa decarboxylase
      inhibitor (> or = 3 daily doses) in patients with idiopathic Parkinson's disease
      and end-of-dose motor fluctuations. The 8-week study included 489 patients under
      conditions of typical daily medical practice. Patients were treated with a 200-mg
      fixed dose of entacapone administered with each scheduled dose of levodopa to a
      maximum of 10 doses per day. Other antiparkinsonian medication should have been
      stable for at least 1 month. The primary efficacy criteria were: (1) Part II
      (activities of daily living, ADL) of the Unified Parkinson's Disease Rating Scale
      (UPDRS), (2) the reduction of 'off' time during the daily waking period as
      assessed by the percentage of patients improving by at least one category at Item
      39 of Part IV of the UPDRS. Secondary outcome measures included: (1) the
      investigator's global assessment of change, (2) quality of life (QoL) was
      assessed using the Parkinson's Disease Questionnaire (PDQ-39). Adverse events,
      vital signs and liver enzymes were monitored at weeks 2 and 8. The baseline mean
      score for ADL was 10.5 (+/-7.04), which decreased to 8.5 (+/-6.37) at the end of
      the study (p < 0.0001). Compared to baseline, 40.8% of patients experienced a
      reduction in 'off' time during the waking period; this improvement was highly
      significant (p < 0.0001). A reduction in the daily dose of levodopa was observed
      in 35.8% of patients (mean decrease 209 +/- 149 mg). QoL was improved by a mean
      of 10% in all categories of the PDQ-39 (p < 0.001), except social support and
      cognition. This improvement was statistically significant (p < 0.001). The
      dyskinesia score (UPDRS Item 32) was decreased significantly from 2.3 to 2.1 from
      baseline to end of study (p < 0.001), although 52.7% of patients reported
      levodopa-induced dyskinesia as an adverse event. There was no case of increased
      liver enzymes. The study results confirm that the excellent risk/benefit ratio
      seen in phase III controlled studies can be seen in daily neurological practice.
      Moreover, the study suggests that the benefits of entacapone are associated with
      a significant improvement in QoL.

PMID- 11244276
TI  - Transient ischaemic attacks and status epilepticus in HTLV-1-negative adult T
      cell leukaemia/lymphoma.

PMID- 11244275
TI  - Common genetic mutations as possible aetiological factors in stroke.

PMID- 11244277
TI  - Apraxia of eyelid closure complicating right parietal infarction.

PMID- 11244278
TI  - Eating seizures in Lennox-Gastaut syndrome.

PMID- 11244279
TI  - Towards a pain treatment based on the identification of the pain-generating
      mechanisms?
AB  - Despite continuous improvements in available pain treatments, many patients with
      chronic pain still remain insufficiently relieved. Although such therapeutic
      failures are often ascribed to pharmacological or psychological factors,
      difficulties in elucidating pain-generating mechanisms may be the main cause of
      insufficient pain management. These difficulties arise from several origins,
      including the unsuitability of the usual classification of pain, the exclusive
      use of etiology or symptom criteria as the main dimension of pain to guide the
      choice of therapeutic agents, the inadequate interpretation of sensory deficit,
      the lack of identification of the injured tissues, the absence of objective pain
      assessment by psychophysical methods. In this paper, we review briefly some
      fundamental knowledge to determine pain treatment based on the identification of
      the physiopathological mechanisms of pain. We advocate that once pain-generating
      mechanisms are known, it becomes possible to establish the appropriate treatment
      of pain.

PMID- 11244280
TI  - Symptomatic differences in decreased alternating motion rates between individuals
      with spastic and with ataxic dysarthria: an acoustic analysis.
AB  - Acoustic analysis was conducted to investigate symptomatic differences in
      decreased oral alternating motion rates (AMRs) between individuals with spastic
      and with ataxic dysarthria. The subjects were 6 individuals with spastic
      dysarthria, 6 with ataxic dysarthria and 6 normal speakers. Monosyllables /pa/
      and /ta/ were used to examine alternating motions of the lips and tongue,
      respectively. In the decreased AMRs of the spastic group, the mean syllable
      durations were generally longer in the individuals where the mean total syllable
      durations were longer, and in the decreased AMRs of the ataxic group, the mean
      gap durations were generally longer in the individuals where the mean total
      syllable durations were longer. It was suggested that each syllable component
      could represent a separate function and contribute differently to the decreased
      AMRs in these dysarthric groups.

PMID- 11244281
TI  - [Multiparametric description of voice quality for normal male and female voices].
AB  - The present study examines the relevance of the voice parameters of two
      commercially available voice analysis programs (MDVP and EGG Program from Kay
      Elemetrics) for the acoustic and electroglottographic definition of normal voice
      profiles for men and women. Vowel productions of 300 adult speakers (150 male and
      150 female speakers) without any known voice pathology were analyzed. In a first
      step, gender-differentiated mean normal voice profiles are presented for each of
      the two analysis programs. The significant differences between the male and
      female speakers indicate the necessity for the separate treatment of the two
      groups. In a second step, a clustering technique differentiates two numerically
      substantial subgroups within each gender on the basis of the MDVP parameters. The
      EGG parameters do not achieve the same degree of subgroup differentiation. In a
      factor analysis, the relative weighting of the MDVP parameters within the factors
      also indicates their better suitability for normal voice differentiation than the
      EGG parameters as they are defined at present.

PMID- 11244282
TI  - Comparisons of speech aerodynamics and lateral craniofacial cephalometrics in
      cleft lip and palate patients with and without Finnish /r/-sound distortion.
AB  - To study the associations between the articulation of the Finnish /r/ sound and
      dentofacial and pharyngeal lateral cephalometric morphology and speech
      physiology, 18 (12 females, 6 males) young adult cleft patients' /r/ sound was
      analysed auditorily by 3 speech experts. Laryngeal resistance (LARE), the
      smallest nasal cross-sectional area (NASA), nasal resistance (NASAR) and
      velopharyngeal orifice area (VEPA) were measured with pressure flow technique,
      and 31 points were identified from the lateral cephalograms to landmark the
      skeletal structure, pharyngeal airway diameters, and position of the hyoid bone.
      The present results showed no significant differences in lateral cephalometric
      skeletal, nasopharyngeal, oropharyngeal or hypopharyngeal morphology between
      subjects with and without /r/-sound distortion. There were no significant
      correlations either between /r/ distortions and NASA, NASAR or VEPA. An
      anteriorly positioned hyoid bone was significantly associated with decreased LARE
      and /r/ distortion. LARE was significantly lower in subjects with /r/ distortion.

PMID- 11244283
TI  - Velopharyngeal function from the age of three to eight years in cleft palate
      patients.
AB  - The purpose of this investigation was to study changes of velopharyngeal function
      between the ages of 3 and 8 years. The subjects were 65 (30 girls and 35 boys)
      Finnish-speaking non-syndromic children with isolated cleft palate (CP, n = 35)
      and with unilateral cleft lip and palate (UCLP, n = 30) operated primarily at the
      age of 1.0-2.0 years. Before the age of 8 years, 16 children required
      velopharyngoplasty (VPP, ad modum Hoenig). The children were followed up for
      speech at the age of 3, 6 and 8 years. The perceptual speech characteristics
      nasal air emission, hypernasality, weakness of pressure consonants and
      compensatory articulations were registered. Indications for a velopharyngeal flap
      (by VPP) were identified on the basis of perceptual speech characteristics and
      confirmed by instrumental examinations. The results indicated that the method and
      timing of primary palatoplasty and sex did not correlate with the quality of
      velopharyngeal function. It was good both in children treated conservatively or
      with VPP at the age of 8 years. The children with a flap required speech therapy
      significantly more often than other children. No child with VPP and only 12% of
      the children without VPP had simultaneous nasal air emissions and hypernasality.
      Compensatory articulation was completely eliminated and weakness of pressure
      consonants was diagnosed only in 1 child without VPP. The CP children required
      significantly more often a velopharyngeal flap than the UCLP children. In
      conclusion, the CP and UCLP children develop a similar velopharyngeal function
      but in a different way.

PMID- 11244284
TI  - Intraoral air pressure discrimination under conditions of partial and complete
      resistance.
AB  - This study assessed a sample of normal-speaking individuals' ability to
      discriminate differences in their self-generated intraoral air pressures. Two
      conditions were employed: (1) open tube in which subjects had to sustain an
      expiratory breath stream to maintain the target pressure, and (2) closed tube in
      which there was complete resistance to the subjects' breath stream. Analysis of
      variance revealed no significant difference (p > 0.05) in subjects' ability to
      discriminate differences in their self-generated intraoral air pressure as a
      function of open or closed tube conditions. However, subjects' discrimination
      scores significantly increased (p < 0.05) as the standard pressure was increased.

PMID- 11244285
TI  - Frontotemporal lobar degeneration. An update on clinical, pathological and
      genetic findings.
AB  - Frontotemporal lobar degeneration is the second most common form of cortical
      dementia in the presenium after Alzheimer's disease. Clinically, based on
      consensus guidelines, three distinct disease entities can be distinguished:
      frontotemporal dementia, semantic dementia and progressive nonfluent aphasia.
      Dementia of frontal type and motor neuron disease inclusion dementia are the most
      frequent neuropathological subtypes of frontotemporal lobar degeneration. By
      using immunohistochemistry, the latter is characterized by the presence of
      filamentous ubiquitin-reactive but tau-negative inclusions in nerve cell bodies
      and neurites. In contrast, Pick's disease and familial frontotemporal dementia
      with parkinsonism linked to chromosome 17 (FTDP-17) are both characterized by
      abundant filamentous nerve cell inclusions made up of the microtubule-associated
      protein tau. The recent discovery of more than 15 different mutations in the tau
      gene in FTDP-17 brought the tau protein to the centre stage. These findings had a
      major impact on our understanding of neurodegenerative disorders characterized by
      tau filamentous inclusions in neurones and/or glial cells which are grouped under
      the generic term of tauopathies. However, as exciting these new molecular
      insights are, it would be inappropriate to lump frontotemporal lobar degeneration
      as tauopathies. Recent neuropathological and genetic data strongly suggest that
      there is more than one genetic background for frontotemporal lobar degeneration.

PMID- 11244286
TI  - Prenatal exposure to a maternal low protein diet shortens life span in rats.
AB  - BACKGROUND: Postweaning diet restriction is associated with prolongation of life
      span, reduced age-related disease and slower ageing. The effects of diet
      restriction imposed prior to weaning have not been so well characterised, but
      studies suggest an opposite effect with increased age-related diseases occurring
      in offspring exposed to undernutrition in prenatal life. It remains unclear
      whether life span is similarly adversely affected by early diet restriction.
      OBJECTIVE: The present study in rats aimed to evaluate the impact of a maternal
      low protein diet upon the life span of the resulting offspring. METHODS: Rat dams
      were fed either a 180-gram casein/kg control diet or a 90-gram casein/kg low
      protein diet from conception until the end of pregnancy. The offspring were then
      maintained with minimal handling until death from natural causes or distress
      necessitated euthanasia. RESULTS: The average life span of female rats exposed to
      low protein diets in utero was reduced by 11% (p = 0.044, Kaplan-Meier analysis).
      There was a similar but non- significant trend in the male offspring (control 76
      +/- 3 weeks, low protein 73 +/- 3 weeks). In addition the rats exposed to a
      prenatal low protein diet had significantly higher systolic blood pressure at 4
      weeks of age and tended to be smaller than control animals in postnatal life.
      CONCLUSION: The results suggest that intrauterine diet restriction reduces life
      span in rats and contrasts with the well-recognised increase in life span
      produced by postweaning diet restriction. The timing of the nutritional
      intervention appears to be critical and recognition of this is relevant to
      understanding the mechanisms underlying the effects of diet restriction on ageing
      and life span.

PMID- 11244287
TI  - The impact of long-term moderate physical activity on functional performance,
      bone mineral density and fracture incidence in elderly women.
AB  - BACKGROUND: Earlier studies have shown that physical exercise and a higher
      workload increase muscle strength and improve gait and balance at all ages for
      both sexes. Published studies have, so far, failed to investigate the functional
      performance of elderly individuals concerning their long-term physical activity
      and variables of daily living. OBJECTIVE: To compare elderly women who
      participate in long-term, moderate exercise programmes with two age-matched
      groups of women from an urban and a rural community. METHODS: All participants
      answered a questionnaire about health, social circumstances and fractures. We
      measured the vibration threshold of the lower extremities, bone mineral density
      of the distal radius and functional performance such as muscle strength, balance
      and gait. RESULTS: The elderly, active groups performed significantly better in
      all functional tests and had sustained fewer fractures than the urban control
      group. When the comparison was made with the rural control group the differences
      were less obvious. The active group rated their health as better than both the
      control groups. CONCLUSION: Elderly women, who continue with moderate exercise
      programmes over many years, sustain fewer fractures and have better muscle
      strength, balance, gait and health ratings than women in general. Whether this is
      the result of the exercise or inherited characters, remains to be proved.

PMID- 11244288
TI  - Isolating the cost of osteoporosis-related fracture for postmenopausal women. A
      population-based study.
AB  - BACKGROUND: Osteoporosis is a condition that will pose an increasing burden on
      health systems as populations age. OBJECTIVE: The objective of this study was to
      estimate the net 'per case' direct medical cost of fracture of indigent women age
      50 years or greater and describe the cost of fracture for Medicaid and Medicare
      payers by inpatient hospital, physician, long-term care, prescription and
      miscellaneous expenditures. METHODS: This study utilized a quasi-experimental
      retrospective interrupted time series design to isolate the economic impact of
      fracture. Administrative claims data for a continuous period of 24 months (12
      months prior to fracture and 12 months after fracture) describing the Medicaid
      and Medicare expenditures for a cohort of women suffering from femur or other
      fracture in 1993 was abstracted and analyzed. ICD-9CM and CPT-4 codes were used
      to identify incident cases of fracture. Interrupted time series regression models
      were estimated using monthly expenditures. RESULTS: A total of 765 Medicaid
      eligible women 50 years of age or greater experienced a fracture in the base year
      and met inclusion criteria. Of these, 226 experienced a femur fracture. The time
      series models detected significant increases in expenditures the month of
      fracture, however, total Medicaid expenditures returned to baseline trend charge
      in 7 and 5 months for femur and nonfemur fracture, respectively. Increases in
      long-term care expenditures persisted throughout the time series, but were offset
      by reductions in other categories of service. CONCLUSION: The net per case costs
      of femur and nonfemur fracture are about USD 3,300 and USD 1,300, respectively.
      The impact of fracture on Medicaid expenditures is temporary as costs rise
      sharply and return to baseline trend charges within a 12-month period.

PMID- 11244289
TI  - Long-term effects of vitamin B(12), folate, and vitamin B(6) supplements in
      elderly people with normal serum vitamin B(12) concentrations.
AB  - BACKGROUND: In the elderly, deficiencies of folate, cobalamin (vitamin B(12)) and
      pyridoxal phosphate (vitamin B(6)) are common. The metabolites homocysteine,
      methylmalonic acid, 2-methylcitric acid and cystathionine have been reported to
      be sensitive markers of these vitamin deficiencies. OBJECTIVE: The long-term (269
      days) effect of an intramuscular vitamin supplement containing 1 mg vitamin
      B(12), 1.1 mg folate, and 5 mg vitamin B(6) on serum concentrations of
      homocysteine (tHcy), methylmalonic acid (MMA), 2-methylcitric acid (2-MCA), and
      cystathionine (Cysta) was studied in 49 elderly subjects with normal levels of
      vitamin B(12). METHODS: Vitamin supplement was administered 8 times over a 21-day
      period, metabolite concentrations were measured until day 269 (e.g. 248 days
      after the end of vitamin supplementation). RESULTS: From day 0 to 21, the serum
      levels of the 3 vitamins increased significantly, after cessation of
      supplementation the levels returned to baseline within the follow-up period. The
      MMA, 2-MCA and tHcy levels decreased during the treatment period significantly
      and did not reach baseline values within the 248-day period. Cysta levels did not
      differ significantly from baseline, either during or after treatment. CONCLUSION:
      MMA and 2-MCA levels rather reflect the availability of vitamins, especially
      cobalamin, than the actual serum levels. Since deficiencies of folate, cobalamin
      and pyridoxal phosphate in the elderly may cause hyerhomocysteinemia and hence
      may have unfavorable effects on mental performance, determination of MMA and 2
      MCA levels in elderly patients with mental disturbances may be a cost-effective
      measure to improve or maintain mental performance.

PMID- 11244290
TI  - The inverse association between age and cholesterol level among older patients:
      the role of poor health status.
AB  - BACKGROUND: The total cholesterol concentration decreases with age in older
      people. The reasons for this phenomenon are controversial. This study
      investigated the hypothesis that poor health status is a determinant of the
      inverse association between age and cholesterol in older persons. METHODS: Cross
      sectional study of 2,486 (53% women) older medical patients (> or =65 years)
      admitted at 35 centers of the Gruppo Italiano di Farmacovigilanza nell'Anziano
      (GIFA) study in Italy. Total cholesterol was measured on the first day after
      admission to the hospital. Disease burden and comorbidity were assessed by the
      Charlson index; low serum albumin and iron were considered markers of frailty and
      poor health. RESULTS: In men there was a significant, inverse age-cholesterol
      relationship (-0.97 mg/dl per year, p<0.001). In women the association was
      nonlinear and cholesterol significantly decreased after the age of 75 (-0.95
      mg/dl per year, p<0.005). In multiple linear regression analysis, indicators of
      poor health accounted for almost two thirds of the crude effect of age on the
      cholesterol level in both men and women (adjusted coefficients for age were: for
      men, -0.38 mg/dl per year, p = 0.044; for women after the age of 75, -0.37 mg/dl
      per year, p = 0.205). The unadjusted probability of having low cholesterol
      significantly increased with age among men (p for trend <0.005). In multiple
      logistic regression, indicators of poor health were strongly associated with low
      cholesterol in both men and women. After adjusting for indicators of poor health,
      the association between age and low cholesterol in men was no longer present.
      CONCLUSION: These findings suggest that the age-dependent reduction of
      cholesterol often observed in clinical and epidemiologic studies is substantially
      explained by the effect of poor health status. Low cholesterol in older persons
      may be a marker of poor health.

PMID- 11244291
TI  - Prognostic impact of plasma brain natriuretic peptide for cardiac events in
      elderly patients with congestive heart failure.
AB  - BACKGROUND: Plasma brain natriuretic peptide (BNP) has been reported to be useful
      in determining the prognosis of patients with ischemic heart disease and
      cardiomyopathy. However, aging increases the level of plasma BNP; therefore, the
      prognostic impact of plasma BNP in elderly patients with congestive heart failure
      has not been fully established. OBJECTIVE: We sought to determine whether plasma
      BNP could predict recurrent cardiac events in elderly patients with congestive
      heart failure. METHODS: Forty-eight consecutive elderly patients (>65 years old)
      were enrolled in the present study. All patients were admitted with their first
      episode of congestive heart failure. Clinical characteristics, plasma BNP, left
      ventricular ejection fraction, and left ventricular mass index were compared
      between patients with and those without recurrent cardiac events. RESULTS: During
      the follow-up period, twelve cardiac events were observed. The New York Heart
      Association functional class was signi- ficantly higher in patients with cardiac
      events than in those without (p < 0.05). The plasma BNP level in pa- tients with
      cardiac events was significantly higher than in those without (521.0 +/- 156.0
      vs. 126.8 +/- 20.1 pg/ml, p<0.001), despite more frequent treatment with
      angiotensin-converting enzyme inhibitors (75 vs. 28%, p<0.05). The left
      ventricular ejection fraction was significantly lower and the left ventricular
      mass index higher in patients with cardiac events as compared with those without
      (38.1 +/- 5.0 vs. 49.2 +/- 2.4%, p < 0.05; 193.8 +/- 14.3 vs. 132.6 +/- 7.8
      g/m(2), p < 0.001, respectively). The plasma BNP was selected as an independent
      factor associated with cardiac events besides New York Heart Association
      functional class, left ventricular ejection fraction, and left ventricular mass
      index using multivariate Cox proportional-hazards regression analysis (hazard
      ratio = 2.656, p<0.05). The cardiac event rate was significantly higher in
      patients with a plasma BNP concentration >132 pg/ml using Kaplan-Meier analysis
      (p < 0.001). Moreover, the plasma BNP level correlated inversely with the length
      of time from hospital discharge to a cardiac event (r = -0.575, p<0.05).
      CONCLUSION: Measuring the plasma BNP level before hospital discharge in elderly
      patients with congestive heart failure was more useful than other conventional
      examinations for predicting the recurrence of cardiac events.

PMID- 11244292
TI  - Scientific breakthroughs: cause or cure of the aging 'problem'.
AB  - Could it be that society's construction of what it means to be elderly has
      created and now fuels the current immortality revolution? Have we defined aging
      in such a manner that we 'need' technological breakthroughs in order to fight the
      'problem' of the soaring geriatric population? This fight may indeed improve
      quality of life and increase longevity, but while doing so, society must accept
      that this strategy will result in an ever increasing elderly population, a
      population that cannot be expected to let beneficient medical technology (comfort
      or cure oriented) pass them by. Society's medical breakthroughs are creating a
      population that ethically we cannot turn our backs on.

PMID- 11244293
TI  - Life in a retirement village: implications for contact with community and village
      friends.
AB  - BACKGROUND: Friends provide acceptance, companionship, emotional support, and are
      important to mental health. One reason that older adults give for seeking
      alternative accommodations is to reduce their loneliness and isolation.
      OBJECTIVE: The purpose of this study was to investigate whether older adults
      living in a retirement village have varying amounts of contact with friends who
      live within the retirement village or in the wider community. METHODS: Three
      hundred and twenty-three independently living residents of 25 retirement village
      sites were interviewed. Participants were asked a range of open and closed
      questions about the amount and kind of contact they had with co-resident friends
      and community-based friends. RESULTS: Residents engaged in several weekly visits
      with village friends and maintained regular contact with community friends
      through telephone calls. Few residents engaged in community outings or
      participated in village activities with either village or community friends.
      CONCLUSION: The nature of living in close proximity with other people, influences
      the amount of informal contact they have with friends. For those older
      individuals who seek alternative accommodation due to isolation or loneliness, re
      location to congregate-style accommodation may increase their social contacts and
      have a positive impact on their well-being.

PMID- 11244294
TI  - Gene therapy in the neuroendocrine system: its implementation in experimental
      models using viral vectors.
AB  - Gene therapy, the transfer of genetic material for therapeutic purposes, has
      undergone an explosive development in the last few years. Within this context,
      development of gene therapy approaches for the neuroendocrine system, while
      incipient, has already generated a core of results which emerge as a promising
      area of research in neuroendocrinology. The present review presents a brief
      description of the viral vector-based gene delivery systems being currently used
      in neuroendocrinology, namely the adenoviral and herpes simplex type-1 (HSV-1)
      derived vector systems, as well as an updated account of neuroendocrine
      pathologies for which gene therapy approaches in animal models are being
      implemented is provided. Current research efforts include treatment of
      experimental pituitary tumors by adenoviral vector-mediated transfer of the
      suicide gene for the HSV-1 thymidine kinase, which converts the prodrug
      ganciclovir into a toxic metabolite. An adenoviral vector encoding the human
      retinoblastoma suppressor oncogene has also been successfully used to rescue the
      phenotype of spontaneous pituitary tumors of the pars intermedia in mice. At the
      hypothalamic level, an adenovirus harboring the cDNA for arginine vasopressin has
      been used in Brattleboro rats to correct diabetes insipidus for several weeks.
      The last part of the review outlines the potential of gene therapy to correct age
      associated neurodegenerative processes at the neuroendocrine level. Although
      effective implementation of gene therapy strategies still faces significant
      technical obstacles, these are likely to be progressively overcome as gene
      delivery systems are being improved.

PMID- 11244295
TI  - A confocal microscopic study of synaptic inputs to gonadotropin-releasing hormone
      cells in mouse brain: regional differences and enhancement by estrogen.
AB  - Even though the cells producing gonadotropin-releasing hormone (GnRH) are
      scattered in the basal forebrain, a large proportion of them is present in the
      organum vasculosum of the lamina terminalis (OVLT) and in the preoptic area. The
      present studies were undertaken to investigate whether there is any difference in
      the number of synaptic inputs between GnRH cells located in the OVLT and those
      located at more anterior levels of the brain. Immunohistochemical staining for
      the synaptic marker synaptophysin coupled with confocal microscopy was employed
      to analyze synaptic inputs to GnRH cells located at the two levels examined. The
      results indicate that GnRH cells in the OVLT region receive a greater number of
      synaptophysin-immunoreactive appositions as compared with those located in the
      anterior septum. This supports the existence of subsets among the GnRH cells
      located in the basal forebrain. The effect of estradiol on the number of
      synaptophysin-immunoreactive appositions onto GnRH cells was also studied.
      Treatment of ovariectomized mice with estradiol significantly enhanced the number
      of synaptophysin-immunoreactive appositions to GnRH cells located at both levels
      examined. Thus the effect of estrogen on GnRH cells may be mediated in part by
      changes in the number of synaptic contacts.

PMID- 11244296
TI  - Dopaminergic input to the ventromedial hypothalamus facilitates the oestrogen
      induced luteinizing hormone surge in ewes.
AB  - In this study we examined the release of dopamine and noradrenaline in the
      ventromedial hypothalamus (VMH) of ovariectomized ewes during the oestrogen
      induced luteinizing hormone (LH) surge by measuring their respective metabolites,
      3,4-dihydroxyphenylacetic acid (DOPAC) and methoxyhydroxyphenylglycol (MHPG)
      using microdialysis. Further we investigated whether inhibition of catecholamine
      synthesis in the VMH by bilateral reverse dialysis of alpha-methyl-p-tyrosine
      (alpha-MPT) would block the oestrogen-induced LH and/or prolactin surges.
      Oestradiol treatment (50 microg oestradiol benzoate) of ovariectomized ewes
      resulted in a biphasic LH response, significantly (p < 0.05) decreasing LH
      concentrations from 2.5 to 10.5 h after injection, followed by an LH surge
      beginning at 16 h. Prolactin concentrations were also significantly (p < 0.05)
      increased in oestradiol-treated ewes from 13 h. VMH DOPAC concentrations in oil
      vehicle-treated animals were at the level of detection (0.02 ng/ml) in most
      samples over the 24-hour sampling period. In oestradiol-treated ewes, VMH DOPAC
      levels were initially low before and up to 8 h after oestradiol injection but
      then increased significantly (p < 0.05) at 10-12 h and remained elevated up to 20
      h after injection. In contrast, oestradiol injection had no effect on MHPG
      concentrations in the VMH. Bilateral reverse microdialysis of alpha-MPT into the
      VMH significantly (p < 0.05) delayed the time from oestradiol injection to the
      onset of the LH surge, the time to peak LH concentration and attenuated the LH
      surge compared with reverse dialysis of Ringer solution alone. In contrast, alpha
      MPT treatment had no effect upon the oestradiol-induced increase in prolactin
      concentrations. This study provides evidence that the VMH is an important
      hypothalamic site in the neuro-endocrine control of the LH surge in ewes. The
      results suggest that dopaminergic neurons with terminals in the VMH are part of a
      neuronal pathway mediating the positive feedback effects of oestradiol on
      gonadotropin-releasing hormone secretion and the LH surge.

PMID- 11244297
TI  - Norepinephrine dialysate levels in the hypothalamic paraventricular nucleus:
      influence on photoperiod-driven prolactin levels in the female siberian hamster.
AB  - Basal prolactin (PRL) levels in Siberian hamsters are modulated by ambient
      photoperiod via the nocturnal melatonin signal. Recent evidence from our
      laboratory has demonstrated that norepinephrine (NE), a putative neurochemical
      regulator of PRL secretion shows photoperiod-dependent fluctuations in the
      hypothalamic paraventricular nucleus (PVN) that are independent of the pineal
      melatonin signal. NE content in the PVN is elevated under a short-day photoperiod
      with a time course that follows the short-day-induced decline in PRL. NE could
      thus modulate the release of a prolactin-releasing factor that subsequently
      drives PRL synthesis and release rates. In order to determine whether NE release
      in the PVN correlates with basal PRL levels, this study evaluated the
      relationship between extracellular NE levels in the PVN and basal PRL under long-
      and short-day photoperiod conditions. In addition, the profile of NE during the
      proestrous surge of PRL was investigated. Female Siberian hamsters were housed
      either in long-day or short-day photoperiods for 8 weeks. After 6 weeks of
      photoperiod exposure, the animals were implanted with a stainless steel guide
      cannula aimed at the PVN. Two weeks later, the animals were fitted with a jugular
      cannula for serial blood sampling and implanted with an indwelling microdialysis
      probe. Dialysis samples were collected every 20 min for 5 h (12.00-17.00 h) from
      short-day-exposed animals and from long-day-exposed animals classified as being
      either in diestrus or proestrus. Blood samples were collected every hour and
      analyzed for PRL levels by radioimmunoassay. NE and methoxy-4-hydrophenylglycol
      (MHPG) levels were significantly higher in short-day-exposed animals, correlating
      with the suppressed basal secretion of PRL. Both long-day groups had lower NE and
      MHPG levels, and higher PRL, than the short-day group. However, long-day animals
      showed a significant decline in NE in proestrus just prior to the onset of the
      afternoon surge of PRL. These data suggest that NE released within the PVN
      participates in the regulation of photoperiod effects upon PRL secretion, as well
      as that of the afternoon surge of PRL on proestrus.

PMID- 11244298
TI  - Estrogen modulates alpha(1)/beta-adrenoceptor- induced signaling and melatonin
      production in female rat pinealocytes.
AB  - Nocturnal rise in pineal melatonin output is due to the night-induced
      acceleration of noradrenergic transmission and alpha(1)- and beta-adrenoceptor
      activation. In addition, in female animals, cyclic oscillations in circulating
      levels of sex steroid hormones are accompanied by changes in the rate of pineal
      melatonin secretion. To investigate whether estrogen directly affects pineal
      adrenoceptor responsiveness, pinealocytes from 21-day-old ovariectomized rats
      were exposed to physiological concentrations of 17beta-estradiol (17beta-E(2))
      and treated with noradrenergic agonists. Direct exposure to 17beta-E(2) reduced
      alpha(1)/beta-adrenoceptor-induced stimulation of melatonin synthesis and
      release. This effect was mediated by an estrogen-dependent inhibition of both
      beta-adrenoceptor-induced accumulation of cAMP and alpha(1)-adrenoceptor-induced
      phosphoinositide hydrolysis. Furthermore, estrogen reduced transient Ca(2+)
      signals elicited in single pinealocytes by alpha(1)-adrenoceptor activation or by
      potassium-induced depolarization. In the case of beta-adrenoceptor
      responsiveness, neither forskolin- nor cholera toxin-induced accumulation of cAMP
      were affected by previous exposure to 17beta-E(2). This indicates that estrogen
      effects must be exerted upstream from adenylylcyclase activation, and independent
      of modifications in G protein expression, therefore suggesting changes in either
      adrenoceptor expression or receptor-effector coupling mechanisms. Since estrogen
      effects upon adrenoceptor responsiveness in pineal cells was not mimicked by
      17beta-E(2) coupled to bovine serum albumin and showed a latency of 48 h, this
      effect could be compatible with a genomic action mechanism. This is also
      consistent with the presence of two estrogen receptor proteins, alpha- and beta
      subtypes, in female rat pinealocytes under the present experimental conditions.

PMID- 11244299
TI  - Lesions of the dorsomedial hypothalamic nucleus do not influence the daily
      profile of pineal metabolism in rats.
AB  - The present study attempted to characterize the effects of electrolytic lesions
      of the hypothalamic dorsomedial nucleus on the daily profile of pineal metabolism
      as well as on the inhibition of pineal melatonin synthesis induced by acute light
      exposure during the night. Adult male Wistar rats (n = 107, 12:12 h light-dark
      cycle) were left intact (n = 47) or lesioned (n = 60). Lesioned rats and their
      respective controls were killed at six time points distributed throughout the
      light-dark cycle. At ZT (zeitgeber time) 18 the animals were killed either in the
      dark or after 15 min of light stimulation. Pineal glands were assayed using high
      performance liquid chromatography with electrochemical detection (HPLC-ED). There
      was no difference in the amounts of pineal indoles between lesioned and control
      rats under any of the experimental situations tested. These results suggest that
      in rats, the hypothalamic dorsomedial nucleus does not participate in either the
      neural control of daily pineal metabolism or the nocturnal light-induced
      inhibition of the pineal metabolism.

PMID- 11244300
TI  - Dorsal and ventral medullary catecholamine cell groups contribute differentially
      to systemic interleukin-1beta-induced hypothalamic pituitary adrenal axis
      responses.
AB  - Medial parvocellular paraventricular corticotropin-releasing hormone (mPVN CRH)
      cells are critical in generating hypothalamic-pituitary-adrenal (HPA) axis
      responses to systemic interleukin-1beta (IL-1beta). However, although it is
      understood that catecholamine inputs are important in initiating mPVN CRH cell
      responses to IL-1beta, the contributions of distinct brainstem catecholamine cell
      groups are not known. We examined the role of nucleus tractus solitarius (NTS)
      and ventrolateral medulla (VLM) catecholamine cells in the activation of mPVN
      CRH, hypothalamic oxytocin (OT) and central amygdala cells in response to IL
      1beta (1 microg/kg, i.a.). Immunolabelling for the expression of c-fos was used
      as a marker of neuronal activation in combination with appropriate cytoplasmic
      phenotypic markers. First we confirmed that PVN 6-hydroxydopamine lesions, which
      selectively depleted catecholaminergic terminals, significantly reduced IL-1beta
      induced mPVN CRH cell activation. The contribution of VLM (A1/C1 cells) versus
      NTS (A2 cells) catecholamine cells to mPVN CRH cell responses was then examined
      by placing ibotenic acid lesions in either the VLM or NTS. The precise
      positioning of these lesions was guided by prior retrograde tracing studies in
      which we mapped the location of IL-1beta-activated VLM and NTS cells that project
      to the mPVN. Both VLM and NTS lesions reduced the mPVN CRH and OT cell responses
      to IL-1beta. Unlike VLM lesions, NTS lesions also suppressed the recruitment of
      central amygdala neurons. These studies provide novel evidence that both the NTS
      and VLM catecholamine cells have important, but differential, contributions to
      the generation of IL-1beta-induced HPA axis responses.

PMID- 11244301
TI  - Bidirectional effects of corticosterone on splenic T-cell activation: critical
      role of cell density and culture time.
AB  - Glucocorticoids inhibit stimulus-induced T-cell proliferation, an early and
      essential parameter of cellular immunity. It was recently found however that
      physiological concentrations of glucocorticoids can also accelerate, not only
      inhibit, rat T-cell mitogenesis. We investigated mechanism(s) underlying
      mitogenic actions of glucocorticoids on anti-T-cell receptor (TCR)- and
      concanavalin A (Con A)-induced T-cell proliferation. Surprisingly, the ability of
      the glucocorticoid corticosterone (CORT) to either enhance or inhibit T-cell
      proliferation was found to depend primarily on the cell density and the timing of
      the cultures. At cell densities up to 1 x 10(5) cells/well (i.e. 'low' density),
      CORT inhibited T-cell proliferation irrespective of the culture time. In
      contrast, at cell densities of 2 x 10(5) cells/well and higher ('high' density),
      CORT potently stimulated T-cell mitogenesis during the first 2-3 culture days,
      but subsequently inhibited the proliferative response after 5-7 days. The
      glucocorticoid receptor antagonist RU486 completely abolished the effects of
      CORT. However, production of the main T cell growth factor interleukin (IL)-2 was
      inhibited by CORT at both 'low' and 'high' cell densities. In addition,
      irrespective of cell density, T-cell mitogenesis under either control conditions
      or in presence of CORT was completely blocked by an anti-IL-2-receptor-alpha
      chain (IL-2Ralpha) antibody, indicating that T-cell proliferation was dependent
      on the IL-2 pathway. Immunofluorescence staining of IL-2Ralpha on CD4+ cells
      after 2-3 days in culture was increased by CORT, but only on cells cultured at
      'high' density. Thus, glucocorticoids increase T-cell responsiveness to IL-2
      under conditions of 'high' cell density only. We conclude that glucocorticoids
      may contribute to a more efficient early stage of cellular immune responses under
      conditions of intimate cell-to-cell contact (i.e. 'high' cell density), a
      situation likely to be present in vivo, for instance in lymph nodes. Thus, these
      findings are relevant to our understanding of the glucocorticoid control of
      immune function.

PMID- 11244302
TI  - A potential role of peritoneal dialysis as 'a bridging therapy' to other renal
      replacement therapies.

PMID- 11244303
TI  - Cell and molecular biology of organic osmolyte accumulation in hypertonic renal
      cells.
AB  - When the renal medulla becomes hypertonic in association with the formation of
      concentrated urine, the cells of the medulla avoid the stress of high
      intracellular salts by accumulating small non-perturbing organic osmolytes. The
      response has been studied in most detail in cultured kidney-derived cells, and
      confirmed in studies of the intact kidney. The non-perturbing osmolytes, myo
      inositol, betaine, and sorbitol, are accumulated because of stimulation of the
      transcription of the genes for the proteins that catalyze their accumulation by
      transport or synthesis. The genes involved have all been cloned and sequenced and
      contain tonicity responsive regulatory elements (TonEs) in their 5' region.
      During hypertonicity, the elements are occupied by TonE-binding protein, a
      transacting factor that has been cloned and characterized. Current efforts focus
      on identifying the mechanism by which cells sense hypertonicity and how that
      leads to activation of TonE-binding protein.

PMID- 11244305
TI  - Lupus nephritis in children: prognostic significance of clinicopathological
      findings.
AB  - BACKGROUND: We aimed to review our experience with childhood lupus nephritis (LN)
      in respect to the analysis of the clinical and histopathological presentation of
      LN and prognostic factors affecting the kidney and patient outcomes. METHOD:
      Forty-three children (39 girls, 4 boys) with biopsy-proven LN were included in
      the study. The mean age of the children was 12.0 +/- 2.8 years. Based on the
      renal histopathology and clinical presentation, patients were treated with oral
      prednisone, intravenous pulses of methylprednisolone or intravenous
      cyclophosphamide. The final clinical status was classified as follows: (1) renal
      and extrarenal remission; (2) clinically active renal disease, or (3) adverse
      outcome, i.e., end-stage renal failure (ESRF) or death. RESULTS: The mean
      duration of follow-up was 7.2 +/- 2.8 years (1 month to 14.2 years). All 43
      children had hematuria and 53.5% had proteinuria at admission. Fourteen children
      were in nephrotic status at the onset of disease. Class IV (diffuse
      proliferative) nephritis was observed in 29 patients as the most frequent
      histopathology (67.4%). The patients with class IV nephritis had a tendency to
      develop nephrotic syndrome, heavy proteinuria, increased Cr levels and persistent
      hypertension at initial evaluation. Thirty-two of 43 children (74.4%) were in
      renal remission at the last visit. Five-year kidney and patient survival rates
      from the time of diagnosis to the endpoints of ESRF or death were 83.7 and 90.7%
      respectively in the whole group while it was 75.9 and 86.2% respectively in the
      class IV group. Adverse outcome was significantly associated with the persistent
      hypertension, anemia, high serum Cr level, heavy proteinuria, nephrotic syndrome
      and class IV nephritis at presentation. CONCLUSION: We can conclude that the
      prognosis of LN in children is primarily dependent on the histopathological
      lesions. Severity of the clinical renal disease at admission and presence of
      persistent hypertension are the main poor prognostic factors rather than age,
      gender, low C3 and C4 levels, ANA positivity and the treatment modalities in
      Turkish children.

PMID- 11244304
TI  - Transforming growth factor-beta1 inhibits vascular permeability factor release by
      T cells in normal subjects and in patients with minimal-change nephrotic
      syndrome.
AB  - BACKGROUND/AIM: A lymphokine, the vascular permeability factor (VPF), which
      increases vascular permeability, has been characterized in minimal-change
      nephrotic syndrome (MCNS). Transforming growth factor-beta (TGF-beta) is an
      immunosuppressive cytokine that inhibits proliferation, cytokine production, and
      cytotoxic activity of T cells and natural killer cells. We, therefore,
      investigated the effects of TGF-beta1 on the release of VPF by peripheral blood T
      cells from MCNS patients. The aim of our study was to determine the in vitro
      immunosuppressive capacity of TGF-beta1 in patients with MCNS. METHODS: To
      further test the effect of TGF-beta1 on concanavalin A (Con A)-induced VPF
      release, normal and MCNS T cells were stimulated with 5 microg/ml of Con A in the
      presence or absence of TGF-beta1, and the culture supernatants were tested for
      the presence of VPF by the method of Lagrue et al. The disease controls included
      16 patients with IgA nephropathy. RESULTS: Significantly increased spontaneous
      and Con A-stimulated secretion of VPF was detected in T-cell cultures of MCNS
      patients with the nephrotic syndrome as compared with those of normal controls.
      Addition of TGF-beta1 to these cultures inhibited the release of VPF in a dose
      dependent manner. The effect of TGF-beta1 on the release of VPF was specific,
      since a reversion was obtained with a neutralizing monoclonal antibody to human
      TGF-beta1. CONCLUSION: Together, our data demonstrate that TGF-beta1 antagonizes
      the ability of T cells to release VPF, and suggest a role of TGF-beta1 in the
      pathophysiology of VPF in vitro.

PMID- 11244306
TI  - Autoantibodies against oxidized LDL in chronic renal failure: role of renal
      function, diet, and lipids.
AB  - Lipid peroxidation (LP) has recently been suggested to trigger the
      atherosclerotic process as well as to worsen the progression of renal disease.
      Autoantibodies against oxidized low-density lipoproteins (Ox-LDLAb) were
      considered to provide a sensitive marker to detect LDL oxidation in vivo. To date
      few studies have been reported on Ox-LDLAb levels in patients with different
      degrees of renal failure. The aim of this study was to evaluate the influences of
      renal function, dietary manipulation, and lipids on Ox-LDLAb concentrations in
      uremic patients either on conservative or replacement therapy. Seventy-one
      patients (42 males, 29 females) aged 60 +/- 19 years with chronic renal failure
      (CRF) of different etiology and degree were divided into four groups according to
      serum creatinine levels [sCr(mg/dl)] and diet: CRF I > or = 1.5-3.0, CRF II > 3.0
      5.5, and CRF III > 5.5 were all patients on a conventional low-protein diet,
      while a fourth group included patients on a vegetarian diet supplemented with
      keto analogues and amino acids (CRF SD >3.0). A further group was represented by
      patients on dialysis therapy. All patients were examined for Ox-LDLAb,
      triglycerides (TG), total cholesterol, HDL and LDL cholesterol, and
      apolipoproteins Apo A1, Apo B, and Lp(a). The results were compared with those of
      20 controls (9 males and 11 females) aged 52 +/- 11 years with sCr <1.5 mg/dl. Ox
      LDLAb increased, although not significantly, with TG and Lp(a) from the early
      stages of CRF along with the deterioration of renal function. However, TG and
      Lp(a) levels were significantly higher in all groups of patients except those on
      vegetarian diet (CRF SD). This group also showed the lowest Ox-LDLAb levels. No
      relationship was observed between lipids or apolipoproteins and Ox-LDLAb.
      Hyperlipidemic patients did not show higher Ox-LDLAb levels than normolipidemics.
      Our results show a progressive increase of LP as the renal function declines,
      which may account for the increased risk of cardiovascular disease reported in
      uremia. Dialysis does not correct significantly the oxidative state observed in
      patients with end-stage renal disease. Vegan diet, by reducing LP, TG, and Lp(a),
      is supposed to decrease the risk of cardiovascular disease and worth being
      reconsidered as an alternative effective therapeutic tool in patients with
      advanced CRF.

PMID- 11244307
TI  - Significance of salivary epidermal growth factor in peptic ulcer disease in
      hemodialysis patients.
AB  - BACKGROUND/AIMS: Hemodialysis (HD) patients are prone to developing peptic
      ulcers. However, of all the risk factors associated with peptic ulcers, none have
      been shown to be more prevalent in HD patients than in the general population.
      However, salivary epidermal growth factor (EGF) may play a role in peptic ulcer
      diseases. METHODS: Salivary EGF levels and bioactivities were assayed in 47
      maintenance HD patients and 30 normal controls, and the molecular weights of EGF
      were assessed using high-performance liquid chromatography (HPLC). RESULTS:
      Salivary EGF levels were not different between both groups of subjects (4.2 +/-
      0.34 vs. 5 +/- 0.54 ng/mg protein, NS), and HPLC revealed that salivary EGF in
      both groups had similar molecular weights. However, salivary EGF bioactivity was
      significantly depressed in the HD patients as compared to the normal controls
      (0.59 +/- 0.08 vs. 1.55 +/- 0.15 ng/mg protein, p < 0.01). Stepwise multiple
      regression showed that the low salivary EGF levels were associated with female
      gender (p < 0.05), while low salivary EGF bioactivity was associated with HD per
      se (p < 0.05). In the 22 HD patients who underwent gastric endoscopy, salivary
      EGF bioactivity was significantly lower in those with peptic ulcers than in those
      without (0.38 +/- 0.08 vs. 0.69 +/- 0.08 ng/mg protein, p < 0.05). CONCLUSION:
      Decreased salivary EGF bioactivity may contribute to peptic ulcer disease among
      maintenance HD patients.

PMID- 11244308
TI  - Prevalence of a novel DNA virus (TTV) among patients on maintenance hemodialysis.
AB  - BACKGROUND/AIMS: A recently detected DNA virus (TTV) has been assumed to be
      responsible for posttransfusion hepatitis in humans. Until now it is unclear
      whether patients on maintenance hemodialysis are at increased risk of acquiring
      TTV. METHODS: Serum samples derived from 143 chronically hemodialyzed patients
      were examined for TTV viremia by nested PCR. All serum specimens were also
      investigated for viremia and for the presence of antibodies of hepatitis C virus
      (HCV) and GB virus C/hepatitis G virus (GBV-C/HGV) by PCR and serological assays,
      respectively. RESULTS: The prevalence of TTV was determined to be 18.8% (n = 27),
      for HCV a prevalence of 15.4% (n = 22) and for GBV-C/HGV of 8.4% (n = 12) could
      be demonstrated. Parallel infection by TTV and HCV was detected in only 1.4% (n =
      2) of the patients. In no serum sample could TTV and GBV-C/HGV be detected in
      parallel. None of the solely TTV-viremic individuals had clinical or biochemical
      signs of liver disease. CONCLUSION: From our data we conclude that TTV viremia is
      widespread among hemodialysis patients and can be detected in 18.8%. Since no
      viremic patient had clinical or biochemical signs of liver disease, the hepatitis
      inducing capacity of TTV remains unclear.

PMID- 11244309
TI  - Haemodialysis and cerebral oedema.
AB  - BACKGROUND: Haemodialysis may cause neurological symptoms ranging from
      inconvenient feelings of disequilibrium to life-threatening neurological
      complications. There are animal data to suggest cerebral swelling may accompany
      haemodialysis and contribute symptomatically to dialysis disequilibrium. However,
      MR images acquired following haemodialysis often fail to demonstrate evidence of
      cerebral oedema. We wished to quantify any potential cerebral volume change which
      is caused by haemodialysis treatment. METHOD: Five renal patients and 5 control
      subjects had a two volumetric T1-weighted MRI scans on the same day. The patients
      were imaged immediately before and after haemodialysis. None were taking
      steroids. Precise positional matching (registration) was used to quantify
      cerebral volume change. RESULTS: Patients had an increase in cerebral volume
      following dialysis which averaged 32.8 ml (SE 7.4 ml, 3% brain volume). The
      change in the controls was 1.4 ml (SE 0.6 ml), p < 0.001. No patient had
      significant neurological symptoms. CONCLUSION: Cerebral oedema developed in the
      patients following dialysis. There is a good biological model for these
      observations. Modifications to dialysis may help. Common problems which increase
      cerebral volume, e.g. acute stroke, require careful appraisal in these patients.
      These observations need consideration when quantifying atrophy in dialysis
      patients.

PMID- 11244310
TI  - L-lysine reduces nonenzymatic glycation of glomerular basement membrane collagen
      and albuminuria in diabetic rats.
AB  - In this study, we examined the hypothesis whether exogenous administration of L
      lysine in drinking water would reduce nonenzymatic glycation of glomerular
      basement membrane (GBM) collagen and thus albuminuria in streptozotocin-diabetic
      rats. The rationale is that the administered lysine would combine with the
      circulating glucose and make it unavailable to react with epsilon-amino groups of
      lysine of various proteins in these diabetic rats. Lysine (0.1%) was given to
      diabetic rats 7 days (early treatment) or 90 days (late treatment) after
      induction of hyperglycemia. The treatment was continued for 60 days. Diabetic
      rats had significantly higher glucose, glycosylated HbA(1), kidney weight,
      nonenzymatic glycation of GBM collagen, albuminuria, and systolic blood pressure
      than normal rats. Early treatment with lysine prevented the rise in glycosylated
      HbA(1) (normal 6.98 +/- 0.71% vs. diabetic - early treatment - 7.78 +/- 1.50%; p
      = NS), reduced glycosylation of GBM collagen by 86%, and significantly improved
      albuminuria. There was no significant effect on plasma glucose and systolic blood
      pressure. However, late treatment reduced the glycosylation of GBM collagen by
      46% with a significant improvement in albuminuria. Plasma creatinine levels were
      not different between normal and untreated diabetic or lysine-treated diabetic
      rats; however, the creatinine clearance was significantly higher in all groups of
      diabetic rats (normal 0.45 +/- 0.09 vs. diabetic 2.02 +/- 0.39 ml/min; p <
      0.001). The data suggest that early rather than late treatment is more beneficial
      in reducing nonenzymatic glycation of collagen, although both treatments
      significantly reduced albuminuria. There was no nephrotoxicity as assessed by
      plasma creatinine levels or creatinine clearances. These beneficial effects
      occurred independent of changes either in blood pressure or plasma insulin
      concentration.

PMID- 11244311
TI  - Low molecular weight heparin reduces proteinuria and modulates glomerular TNF
      alpha production in the early phase of adriamycin nephropathy.
AB  - BACKGROUND/AIM: Heparin has been shown to be renoprotective in a number of
      experimental nephropathies. The inflammatory component in the early phase of
      Adriamycin (ADR) induced nephropathy has been established. A microdose of low
      molecular weight heparin (Fragmin; F) has been noted to exert immunomodulatory
      effects independent of its anticoagulant activity. We assessed the effects of
      microdoses of F on daily proteinuria and glomerular production of tumor necrosis
      factor alpha (TNF-alpha) and prostaglandins 8 and 15 days after induction of ADR
      nephropathy. METHODS: Following intravenous injection of ADR (7 mg/kg) to Wistar
      rats weighing 200 +/- 20 g, F 20 microg/day/rat s.c. was administered for 8 and
      15 days (groups F8 and F15). The respective control groups (C8 and C15) received
      normal saline subcutaneously. Proteinuria, serum albumin, and creatinine
      clearance were evaluated on days 8 and 15. The production of TNF-alpha and
      prostaglandins from glomerular supernatants was measured by radioimmunoassay on
      days 8 and 15. RESULTS: F significantly reduced proteinuria (mg/day) on day 8:
      13.6 +/- 1.2 in F8 versus 40.3 +/- 2.7 in C8 (p = 0.008). The glomerular
      production of TNF-alpha (pi/ml) was significantly lower on day 8 in rats treated
      with F: 356 +/- 33 in F8 versus 764 +/- 81 in C8 (p = 0.006). A decrease in the
      prostaglandin E2/thromboxane B2 ratio was noted in the F group between 8 and 15
      days (1.1 in F8 vs. 0.9 in F15, p = 0.005) which principally reflects an increase
      of thromboxane B2. The antiproteinuric effect of F shown after 8 days was no
      longer present after 15 days (354 +/- 91 mg/day in F15 vs. 499 +/- 69 mg/day in
      C15, p = 0.33). The same trend was seen for the glomerular production of TNF
      alpha. Light microscopy and immunohistochemistry for interstitial and glomerular
      macrophages were negative. CONCLUSION: The lowering effect of microdoses of F on
      the proteinuria seen during the early phase of ADR nephropathy may be mediated by
      a decreased production of glomerular TNF-alpha, supporting the anti-inflammatory
      action of low molecular weight heparin.

PMID- 11244312
TI  - Effects of endothelin receptor antagonists on the progression of diabetic
      nephropathy.
AB  - BACKGROUND: Diabetic nephropathy is the leading cause of end-stage renal disease
      in European countries and is associated with an enhanced renal synthesis of
      endothelin (ET)-1. ETs are - beside their potent vasoconstrictor properties -
      very potent profibrotic acting paracrine hormones especially in the kidney.
      METHODS: We analyzed in rats with streptozotocin-induced diabetes the effects of
      an ETA-type (ETA) receptor antagonist (LU 135252) in comparison to a combined
      ETA/ETB receptor antagonist (LU 224332) on the expression of interstitial and
      glomerular collagen type I, III and IV as well as on fibronectin and laminin by
      quantitative immunohistochemistry using a computer-aided image analysis system.
      Global glomerular matrix deposition was analyzed after PAS staining. In addition
      to the morphometric examination of the kidneys, we also investigated GFR, urinary
      albumin and total protein excretion. The diabetic rats were treated for 36 weeks.
      RESULTS: Treatment with either LU 135252 or LU 224332 normalized the amount of
      PAS-positive material within the glomeruli. The expression of glomerular
      fibronectin and type IV collagen was increased 36 weeks after induction of
      diabetes. The overexpression of these two matrix proteins within the glomeruli of
      diabetic rats was completely abolished by both ET receptor antagonists, whereas
      protein excretion was only reduced by about 50% as compared to diabetic rats
      without treatment. CONCLUSION: The present study indicates that ETA receptor
      antagonists as well as combined ETA/ETB receptor antagonists reduce proteinuria
      and completely normalize the renal matrix protein expression in hyperglycemic
      rats with streptozotocin-induced diabetes. The antifibrotic effect seems to be
      mediated via the ETA receptor. ET receptor antagonists might be a new approach in
      the treatment of diabetic nephropathy.

PMID- 11244313
TI  - Effects of allopurinol on renal stone formation and osteopontin expression in a
      rat urolithiasis model.
AB  - BACKGROUND: The inhibitory effect of allopurinol on calcium oxalate urolithiasis
      has been reported, but its effect on stone matrix proteins has not been studied
      in vivo. To clarify the effect of allopurinol on the matrix, we investigated its
      effect on the expression of osteopontin (OPN), which we previously identified as
      an important stone matrix protein. METHODS: Control rats were not treated. Rats
      of the stone group were given ethylene glycol (EG) and vitamin D(3), while the
      allopurinol groups (low-dose group and high-dose group) were treated with
      allopurinol in addition to receiving EG and vitamin D(3). RESULTS: The rate of
      renal stone formation was lower in the allopurinol groups than in the stone
      group. This was associated with a low expression of OPN mRNA in allopurinol
      treated rats relative to that in the stone group. CONCLUSION: Allopurinol was
      effective in preventing calcium oxalate stone formation and reduced OPN
      expression in rats. Our results suggest that allopurinol prevents renal stone
      formation by acting against not only the control of oxalate but also OPN
      expression.

PMID- 11244314
TI  - Reversible nephrotic syndrome in a patient with amyloid A amyloidosis of the
      kidney following methicillin-resistant Staphylococcus aureus infection.
AB  - A common form of methicillin-resistant Staphylococcus aureus (MRSA) associated
      glomerulonephritis is either an endocapillary proliferative glomerulonephritis or
      a crescentic glomerulonephritis. This report describes the development of
      reversible nephrotic syndrome following MRSA infection in a patient with amyloid
      A amyloidosis. The patient had been diagnosed as having rheumatoid arthritis for
      50 years. Suppurative arthritis due to MRSA became complicated 2 years prior to
      admission to our hospital. In the meantime, a nonnephrotic-range proteinuria
      developed. Two weeks before admission, nephrotic syndrome developed. The serum
      creatinine level remained unchanged throughout the course, but common features
      characteristic of MRSA-associated glomerulonephritis were observed in this
      patient, such as elevated serum IgG and IgA levels. A renal biopsy specimen
      showed glomerular amyloid A amyloidosis of a nodular type, infiltrated
      mononuclear cells in the mesangium, deposition of IgG, IgA, and C3, and swelling
      of glomerular endothelial cells. There were no crescentic glomeruli. Following
      surgical eradication of the MRSA focus in the right knee joint, nephrotic
      syndrome disappeared. Hence, it was highly possible that MRSA infection induced a
      reversible nephrotic syndrome by causing reversible injuries to glomerular
      endothelial cells. The description of this case serves to illustrate the range of
      MRSA infections that may cause various forms of glomerulonephritides.

PMID- 11244315
TI  - Apoptosis of renal tubular cells in Shiga-toxin-mediated hemolytic uremic
      syndrome.
AB  - In order to clarify the mechanism of unusual renal tubular dysfunction seen in a
      child with Shiga toxin (Stx)-mediated hemolytic uremic syndrome (HUS), we studied
      the renal biopsy specimens for Stx binding and apoptosis of renal tubular cells.
      A 7-year-old boy with Stx-2-mediated HUS demonstrated extensive renal tubular
      damage characterized by nonoliguric acute renal failure, increased urinary
      tubular enzymes and defective urine-concentrating capacity. His renal biopsy
      specimens were analyzed for Stx binding and apoptotic cell death. Seven kidney
      tissue specimens obtained from patients without HUS served as controls. Detection
      of Stx binding to renal sections and apoptotic cells were performed using mouse
      monoclonal anti-Stx 2 antibody and the TUNEL method, respectively. Positive
      staining was observed predominantly in renal tubular cells, while the 7 kidney
      tissue specimens from control patients did not show positive staining. To the
      best of our knowledge, this is the first case to show Stx binding and apoptotic
      cell death in renal tubules on biopsy specimens obtained from a child with Stx
      mediated HUS. In conclusion, this case suggests that vascular endothelial cells
      are not the sole nor the consistent target for Stx-mediated cell injury and that
      significant renal tubular damage other than glomerular damage might occur in some
      children with Stx-mediated HUS.

PMID- 11244316
TI  - Pharmacokinetics of ritonavir and saquinavir in a haemodialysis patient.

PMID- 11244317
TI  - An unusual complication of nephrotic syndrome: chylothorax treated with
      hemodialysis.

PMID- 11244318
TI  - Recurrent glomerulonephritis in relapsing polychondritis.

PMID- 11244319
TI  - Effect of cyclophosphamide or azathioprine on urinary podocytes in patients with
      diffuse proliferative lupus nephritis.

PMID- 11244320
TI  - Effect of mizoribine on serum IgE concentration in patients with IgA nephropathy.

PMID- 11244321
TI  - The role of extracellular glutathione peroxidase in diabetic nephropathy.

PMID- 11244322
TI  - Intolerance to ACE-inhibitor drugs.

PMID- 11244323
TI  - Treatment of advanced stage Hodgkin's disease.
AB  - Hodgkin's disease remains one of the few malignant diseases which can be cured by
      modern chemotherapy in most cases even in advanced stages. Adriamycin-containing
      chemotherapy regimens are considered as the standard therapy which induce long
      term remission in about 60-70% of patients. The ABVD scheme, developed by
      Bonadonna and colleagues in Milan, has a favorable toxicity profile and causes
      less myelotoxicity, acute leukemia or sterility relative to many previous
      treatment programs containing alkylating agents. However, 20- 30 % of patients
      eventually relapse and are then frequently treated with high-dose programs
      including stem cell transplantation. There are two major goals in advanced
      Hodgkin's disease: (1) to improve the cure rate and (2) to reduce acute and long
      term toxicities. The recent definition of prognostic factors identified patients
      who are at a high risk of treatment failure as well as those in whom less toxic
      approaches can be applied. The optimal approach or program has not yet been
      defined, although new chemotherapy regimens such as BEACOPP and Stanford V with
      increased tumor response rates have been identified. These new drug combinations
      are currently analyzed and compared with ABVD in several international trials.
      While the addition of radiotherapy improved disease control in some trials a
      survival benefit was not identified and the role of radiotherapy remains
      controversial. High dose programs remain experimental in advanced stage Hodgkin's
      disease and should be restricted to prospective clinical trials.

PMID- 11244324
TI  - Phase II trial of systemic recombinant interleukin-2 in the treatment of
      refractory nasopharyngeal carcinoma.
AB  - BACKGROUND: Interleukin-2 (IL-2) is a cytokine produced by activated T cells,
      which has shown powerful immunostimulatory and antineoplastic properties.
      Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus-associated cancer with
      abundant lymphocyte infiltration histologically. The activity of IL-2 in the
      treatment of NPC patients is currently unknown. A phase II study was, therefore,
      initiated to evaluate the efficacy, toxicity and immunological consequences of
      intravenous bolus IL-2 in patients with recurrent/metastatic NPC. METHODS:
      Between November 1996 and April 1997, 14 patients with recurrent/metastatic NPC
      were entered into the study. Recombinant IL-2 (Proleukin, Chiron) was injected by
      intravenous bolus every 8 h at 72,000 IU/kg for a maximum of 15 doses. After 7
      days, patients were retreated with a second identical cycle of therapy. Those
      patients who were stable or responding to treatment 5-6 weeks later went on to
      receive another course (two cycles) of therapy. All patients received
      prophylactic antibiotics and antipyretic medicine. Response and toxicities were
      evaluated. Serial plasma level of TNF-alpha, IL-6, soluble IL-2 receptor, IL-10
      and soluble CD8 were determined. RESULTS: Fourteen patients received a total of
      34 cycles of therapy. No response was observed. Fifty percent had stable disease,
      50% had progressive disease after a median of two cycles of therapy. There was
      one treatment-related death from acute myocardial infarction. Body weight
      increase (>5%) occurred in 80% of cycles, and hypotension (BP <80 mm Hg systolic)
      occurred in 53%. Serum creatinine increase (>2 mg%) occurred in 24% of cycles,
      and SGOT/SGPT increase (>3x) in 10% of cycles. Symptoms of somnolence, general
      malaise, nausea and vomiting, pruritus, xerostomia, desquamation were generally
      mild to moderate but rapidly reversible. CONCLUSION: The single modality of
      intravenous bolus IL-2 at the dose level of 72,000 IU/kg is clinically
      ineffective in NPC patients. Potential mechanisms of the ineffectiveness of IL-2
      therapy on NPC patients are discussed.

PMID- 11244325
TI  - Paclitaxel by 72-hour continuous infusion followed by bolus intravenous
      ifosfamide or epirubicin: results of two phase I studies.
AB  - STUDY PURPOSES: To determine the maximum-tolerated dose (MTD) of paclitaxel
      administered by 72-hour continuous infusion followed by bolus intravenous
      ifosfamide on days 4 and 5 or epirubicin on day 4, every 21 days. To assess the
      toxicity and preliminary activity in patients with advanced refractory solid
      tumors. PATIENTS AND METHODS: Sixteen patients with progressive disease after
      standard chemotherapy for advanced disease were treated with the combination
      paclitaxel-ifosfamide and 10 patients with the combination paclitaxel-epirubicin.
      RESULTS: In the first phase I study the MTDs were: paclitaxel 135 mg/m2 and
      ifosfamide 2.5 mg/m2/day; hematologic toxicity was the dose-limiting toxicity
      (DLT) during the first cycle of therapy at dose level 4. Paclitaxel administered
      at 135 mg/m2 and epirubicin 50 mg/m2 were the MTDs in the second phase I study;
      grade 4 stomatitis was the DLT of this combination. CONCLUSIONS: Paclitaxel by 72
      hour continuous infusion followed by bolus ifosfamide was a manageable regimen
      with an acceptable hematologic toxicity in the absence of neurotoxicity.
      Preliminary activity of this combination was encouraging in a group of patients
      with ovarian cancer. The optimal way to combine paclitaxel and epirubicin and the
      best schedule relative to such a long paclitaxel infusion time in this
      combination regimen remain to be determined.

PMID- 11244326
TI  - Tumor 'flare' hypercalcemia--an additional indication for bisphosphonates?
AB  - The most serious, potentially life-threatening manifestation of 'flare' is
      hypercalcemia, registered in 4-5% of breast cancer patients with bone metastases,
      usually during the first few weeks of tamoxifen treatment. There are no specific
      treatment recommendations for flare hypercalcemia, except tamoxifen withdrawal.
      There are no reports on the use of bisphosphonates in the treatment of flare
      hypercalcemia. Among 87 hypercalcemic patients with metastatic breast cancer
      observed during a 7-year period, 10 patients had tamoxifen-induced hypercalcemia.
      Diagnosis of flare hypercalcemia was based on the normal pretreatment values of
      serum calcium and the development of hypercalcemia within a maximum of 6 weeks of
      hormonal drug initiation. The median time from hormonal drug initiation to flare
      hypercalcemia was 14 days, the median duration 8.5 days, and the median calcium
      level was 3.09 mmol/l (range 2.79-4.46 mmol/l). All patients were treated with
      hydration, and 7 patients with calcium levels above 3.0 mmol/l were also treated
      with disodium pamidronate in various single doses (30-90 mg/24 h). Normocalcemia
      was achieved in all patients, and tamoxifen was continued without relapse of
      hypercalcemia. Median survival was 177 days (range 12-570 days). It seems that
      the use of bisphosphonates in the treatment of flare hypercalcemia could allow
      safe readministration of tamoxifen and prevent premature and unjustified
      tamoxifen discontinuation. Flare hypercalcemia might represent one more
      indication for the use of bisphosphonates.

PMID- 11244327
TI  - Irinotecan and mitomycin C in 5-fluorouracil-refractory colorectal cancer
      patients. A phase I/II study of the Southern Italy Cooperative Oncology Group.
AB  - PURPOSE: To define the maximum tolerated dose (MTD) of irinotecan (CPT-11) given
      on days 1 and 8 with mitomycin C (MMC) given on day 1 in a monthly cycle, and to
      assess the toxicity and activity of this regimen in patients with previously
      treated colorectal carcinoma. METHODS: Fifty-two patients, all pretreated with
      adjuvant 5-fluorouracil (20 patients) and/or one (35 patients) or two (8
      patients) lines of chemotherapy, were entered in this study. Escalating doses of
      CPT-11 (starting from 150 mg/m2) were administered on days 1 and 8, with
      escalating doses of MMC (starting from 8 mg/m2) given on day 1, recycling every
      28 days. At least 3 patients were treated at each dose level. Escalation
      proceeded unless 2 out of 3 or 4 out of 6 patients experienced a dose-limiting
      toxicity (DLT) after the first cycle. RESULTS: Twelve patients were entered in
      the phase I study, and 4 consecutive dose levels were tested. At the last dose
      level (CPT-11 200 mg/m2 plus MMC 10 mg/m2) 4 of 6 patients experienced a DLT
      (i.e., grade 4 neutropenia in 2 patients and grade 3 diarrhea in 2 patients).
      Therefore, this dose level was considered as the MTD. Forty patients were treated
      at the previous dose level (CPT-11, 175 mg/m2 plus MMC 10 mg/m2). One complete, 4
      partial, 3 minor responses and 11 cases of stable disease were registered, giving
      a response rate of 12% [95% confidence interval (CI), 4-27%] and an overall
      control of tumor growth in 47% (95% CI, 31-64%) of patients. The median time to
      treatment failure was 6 months (range 1-19+). The median survival time was 14.5
      months, and the 1-year and 2-year probability of survival were 56 and 43%.
      Neutropenia and diarrhea affected 62 and 58% of patients, grade 3 or 4 being
      registered in 26 and 23% of them, respectively. One episode of neutropenic fever
      was reported. Other acute toxicities were usually mild and manageable.
      CONCLUSIONS: CPT-11 175 mg/m2 on days 1 and 8 associated with MMC 10 mg/m2 on day
      1, every 4 weeks, is a safe and moderately active regimen in heavily pretreated
      patients with advanced colorectal carcinoma. The role of MMC in this combination
      is doubtful, and further attempts with other new agents should be made to improve
      the outcome in these patients.

PMID- 11244328
TI  - Combined treatment with high-dose methotrexate, vincristine and procarbazine,
      without intrathecal chemotherapy, followed by consolidation radiotherapy for
      primary central nervous system lymphoma in immunocompetent patients.
AB  - OBJECTIVES: To assess the feasibility and the activity, as well as the efficacy
      to treat meninges, of chemotherapy (CHT) containing high-dose methotrexate (HD
      MTX) followed by radiation therapy (RT), without intrathecal CHT, in patients
      with primary central nervous system lymphoma. METHODS: Eligibility criteria were
      histologically proven diagnosis, disease limited to the CNS, age < or = 70, ECOG
      performance status < or = 3, HIV-negative and no prior treatment. Thirteen
      patients (1996-1999; median age 54 years) received two courses of vincristine 1.4
      mg/m2 day 1, MTX 3 g/m2 days 3 and 10 and procarbazine 100 mg/m2 days 1-14 every
      4 weeks. Patients who achieved a complete remission were referred to RT, those
      with progressive disease were excluded from further study; all the remaining
      patients received a third course of CHT followed by RT. RESULTS: Twelve patients
      responded to CHT (overall response rate = 92%, complete response rate = 77%): 9
      underwent consolidation RT, 3 did not. Two patients experienced severe acute
      toxicity; lethal pulmonary thromboembolism and transient renal failure. Five
      patients relapsed: 2 after CHT and 3 after RT. Relapse was local in all cases,
      with a case of concomitant hepatic involvement. No cases of ocular or meningeal
      relapse were observed. In contrast to high-dose cytarabine-containing CHT,
      salvage therapy with temozolomide produced good results. Two patients died of
      treatment-related neurotoxicity. Six patients are alive with a median follow-up
      of 17 months, and a 2-year overall survival (OS) of 61%. The median survival of
      the 9 patients who completed the planned treatment is 25+ months with a 2-year OS
      of 80%. CONCLUSIONS: HD-MTX, procarbazine and vincristine followed by RT, without
      intrathecal therapy, produce similar results with respect to other HD-MTX
      containing regimens. These results seem to suggest that adequate meningeal
      treatment is possible without intrathecal drug delivery, even in CSF-positive
      patients. Corroborating data from a larger series are, however, necessary.
      Temozolomide should be tested in relapsed patients in a phase II prospective
      trial.

PMID- 11244329
TI  - Different response to the long-acting somatostatin analogues lanreotide and
      octreotide in a patient with a malignant carcinoid.
AB  - INTRODUCTION: Somatostatin (SST) analogues are cornerstones in the symptomatic
      management of patients suffering from carcinoid tumors, and antiproliferative
      activity has also been reported for these agents. The most commonly applied SST
      analogues are octreotide (OCT) and lanreotide (LAN), which are both available in
      a slow release formulation. To the current knowledge, both OCT and LAN are
      thought to be equally effective for the management of various disorders. We
      report the case of a patient with a disseminated carcinoid, who progressed during
      dose-intensified treatment with slow-release LAN in combination with interferon
      alpha, but developed a pronounced response after treatment was switched to the
      application of a depot formulation of OCT. CASE REPORT: A 46-year-old woman was
      admitted to our department for the evaluation of persistent flushing, diarrhea
      and dyspnea. After a diagnosis of metastatic carcinoid had been established,
      treatment with LAN (30 mg i.m. every 10 days) along with interferon-alpha 3 x 5
      MU/week was initiated. In spite of successful blocking of tumoral SST receptors
      as judged by SST receptor scintigraphy and subjective improvement of symptoms,
      the patient had progressive disease. As she refused chemotherapy, treatment was
      switched to a depot formulation of OCT (20 mg i.m. every 4 weeks), resulting both
      in a disappearance of symptoms as well as tumor regression as seen on CT
      scanning. CONCLUSION: To our knowledge, this is the first case demonstrating both
      a symptomatic as well as objective response to OCT following progression during
      therapy with LAN in a patient with a carcinoid tumor. Our results suggest that
      refractoriness to treatment including a long-acting SST analogue does not
      automatically imply resistance to a related agent and should alert clinicians to
      the potential of non-cross-resistance between SST analogues in neuroendocrine
      malignancies.

PMID- 11244330
TI  - Overexpression of vascular endothelial growth factor C is related to lymphogenous
      metastasis in early gastric carcinoma.
AB  - Vascular endothelial growth factor C (VEGF-C) is considered to be potentially
      lymphangiogenic and can selectively induce hyperplasia of the lymphatic
      vasculature. In this study, we clarified the clinicopathological features of
      early gastric carcinoma (EGC) that has metastasized to the lymph nodes, as well
      as the correlation between lymphogenous metastases in EGC and the expression of
      VEGF-C and VEGF. We selected 35 cases of lymph node metastasis-positive [n(+)]
      EGC and 70 cases of lymph node metastasis-negative [n(-)] EGC for the present
      study. The expression of VEGF and VEGF-C was investigated with
      immunohistochemical staining using monoclonal antibodies against VEGF and VEGF-C.
      Clinicopathologically, there were significant differences in median size (4.1 +/-
      2.4 vs. 2.4 +/- 1.7 cm), lymphatic invasion (54 vs. 4%) and venous invasion (23
      vs. 3%) between n(+) EGC and n(-) EGC. Immunohistochemically, the incidence of
      positive expression of VEGF-C in lymphatic invasion-positive EGC (36%) was
      significantly higher than that in lymphatic invasion-negative EGC (14%). The
      incidence of positive expression of VEGF-C in n(+) or venous invasion-positive
      EGC tended to be higher than that in n(-) or venous invasion-negative EGC. In
      conclusion, lymphatic invasion was significantly increased in VEGF-C-positive
      EGC.

PMID- 11244331
TI  - A comparison of DNA copy number changes detected by comparative genomic
      hybridization in malignancies of the liver, biliary tract and pancreas.
AB  - Tumors arising from the liver, biliary tract and pancreas, which originate in the
      foregut and are in close anatomical proximity to each other, sometimes show
      similar histological features. No studies have focused on genetic similarities
      and differences between tumors of these organs. To elucidate the similarities and
      differences in DNA copy number alterations between tumors of these organs, we
      applied comparative genomic hybridization (CGH) to cancers of the liver (31
      cases), biliary tract (42 cases) and pancreas (27 cases). Some alterations were
      common to tumors of all three organs, and some were preferential in certain types
      of tumor. Gains of 1q and 8q and losses of 8p and 17p were common to all tumors.
      In contrast, 13q14 and 16q losses were detected exclusively in hepatocellular
      carcinomas (HCCs; p < 0.01). The incidence of 17q21 gain and 5q loss was higher
      in biliary tract cancers than in the other two types (p < 0.05). Pancreatic
      cancers exhibited higher incidence of 5q14-q23 gain and 19p loss than tumors of
      other organs (p < 0.01). Gains of 7p, 7q, 12p and 20q and losses of 3p, 6q, 9p
      and 18q were frequent in both biliary tract and pancreatic cancers but rare in
      HCCs (p < 0.05). The present results suggest that although genes located at 1q,
      8p, 8q and 17p are frequently involved in HCC, biliary tract and pancreatic
      cancer, at least some of the genes implicated in carcinogenesis are different
      between these three types. It is also suggested that CGH analysis is useful as a
      potential adjunct for the diagnosis and management of these tumors of organs that
      are anatomically close to one another.

PMID- 11244332
TI  - Clinical significance of human erythrocyte glucose transporter 1 expression at
      the deepest invasive site of advanced colorectal carcinoma.
AB  - OBJECTIVE: Malignant cells exhibit increased glucose uptake and utilization in
      vitro and in vivo. This process is thought to be mediated by the glucose
      transporter (Glut) family. The aim of this study was to elucidate the clinical
      significance of Glut1 expression at the site of deepest invasion as a predictor
      of the invasive/metastatic potential and prognosis of advanced colorectal
      carcinoma (CRC). METHODS: One hundred and fifty-two patients who had undergone
      surgical resection for advanced CRC were entered in this study. Histologic
      subclassifications at the deepest invasive site included well-differentiated (W),
      moderately to well-differentiated (Mw), moderately to poorly differentiated (Mp),
      poorly differentiated (Por) and mucinous (Muc) adenocarcinomas. Glut1 expression
      was examined immunohistochemically with a labeled streptavidin-biotin kit using
      anti-Glut1 polyclonal antibody MYM. As a marker of cell proliferation, Ki-67
      expression was also examined. All immunoreactivity was analyzed at the deepest
      invasive site, central portion and superficial part. The immunohistochemical
      expression of Glut1 was defined as positive if distinct staining of the membrane
      or cytoplasm was observed in at least 30% of tumor cells. RESULTS: Glut1
      expression was detected in 56 of 152 lesions (36.8%) at the deepest invasive
      site. The incidence of Glut1 expression at the deepest invasive site correlated
      significantly with histologic grade (W/Mw grade, 28% vs. Mp/Por/Muc grade, 48%),
      depth of invasion (invasion of muscularis propria/invasion of subserosa or
      subadventitia, 29% vs. invasion of serosa or adventitia/invasion of adjacent
      structures, 52%), lymphatic invasion (absence of lymphatic invasion, 19% vs.
      presence of lymphatic invasion, 40%), lymph node metastasis (absence of lymph
      node metastasis, 25% vs. presence of lymph node metastasis, 41%) and Duke's stage
      (Duke's <D, 32% vs. Duke's D, 51%). In the central portion and superficial part,
      there were no significant differences between Glut1, Ki-67 expression and
      clinicopathological findings. Glut1 expression at the deepest invasive site
      correlated significantly with the Ki-67 labeling index. In cases of curative
      surgery, patients with Glut1-positive lesions at the deepest invasive site showed
      a significantly poorer prognosis than those with Glut1-negative lesions.
      Multivariate analysis with logistic regression for 5-year survival in patients
      who had undergone curative surgery showed that lymph node metastasis and Glut1
      expression were significant risk factors. CONCLUSION: These results indicate that
      Glut1 expression at the deepest site of tumor invasion can be a useful predictor
      of a high malignant potential and poor prognosis in advanced CRC.

PMID- 11244333
TI  - Micrometastatic p53-positive cells in the lymph nodes of early stage epithelial
      ovarian cancer: prognostic significance.
AB  - We used immunohistochemical staining of p53 protein to detect micrometastasis in
      regional lymph nodes that were judged tumor-free by conventional
      histopathological methods in 58 patients with stage I or II (pT1 or 2, N0)
      epithelial ovarian cancer. Overexpression of p53 protein in the primary lesions
      of ovarian cancer was observed in 31 patients (53%), and p53 protein-positive
      cells were detected in the regional lymph nodes (micrometastasis-positive) in 19
      of 31 patients with p53 protein overexpression (61%). In patients with
      micrometastasis, the prognosis was significantly poorer than that in those
      without micrometastasis (p < 0.05). Detection of micrometastasis of the regional
      lymph nodes of ovarian cancer by immunohistochemical staining of p53 protein may
      be useful in predicting the prognosis of patients with stage I or II epithelial
      ovarian cancer.

PMID- 11244334
TI  - Evaluation of methods to detect p53 mutations in ovarian cancer.
AB  - OBJECTIVE: The p53 status is increasingly regarded as a marker predictive of
      response to particular cancer therapies, but for this approach it is self-evident
      that the p53 status must be determined correctly. METHODS: We have tested ovarian
      cancers with single-strand conformation polymorphism analysis (SSCP),
      immunohistochemical staining with DO-1 anti-p53 antibody (IHC), and yeast p53
      functional assay (FASAY). RESULTS: These techniques commonly used to detect p53
      mutations showed important differences in their sensitivity. Of 53 tumors tested
      with three indirect techniques, 27 (50%), 33 (62%) and 41 (77%) were positive by
      SSCP, IHC, and FASAY, respectively. In a subset of 32 tumors strongly suspected
      of containing mutations, 25 (78%), 26 (81%), 29 (91%) and 30 (94%) were positive
      by SSCP, immunostaining, DNA sequencing and yeast assay, respectively.
      CONCLUSIONS: Under comparable routine conditions, the FASAY reached the highest
      sensitivity. Since no single technique detected all mutations, we recommend the
      use of at least two different techniques in situations where the p53 status will
      affect patient management.

PMID- 11244335
TI  - Corneal manifestations of systemic diseases. Part 2.

PMID- 11244336
TI  - Conversion formulas between automated-perimetry indexes as measured by two
      different types of instrument.
AB  - PURPOSE: Comparison between the results of measurements made using different
      types of automated-perimetry equipment is difficult, because of the lack of
      standardisation. The purpose of the study was to compare the two main indexes,
      mean deviation or mean defect (MD) and pattern standard deviation (PSD), as
      measured by two widely used instruments (Interzeag Octopus 500EZ and Humphrey
      Field Analyser 740) in the same group of patients. PATIENTS AND METHODS: Thirty
      eyes of 17 patients with different stages of primary open-angle glaucoma were
      tested, and for 25 eyes the indexes measured using program G1 of the Octopus
      perimetry instrument were compared with those from program C30-2 of the Humphrey
      Field Analyser. RESULTS: Using the one-tailed Student t test, a significant
      difference was found between the MD and the PSD values of the Humphrey and of the
      Octopus perimetry equipments. However, subsequent use of the conversion formulas
      to adjust the measurements then indicated a good correlation between the two
      instruments (MD: r = 0.91; PSD: r = 0.79). CONCLUSION: MD and PSD values measured
      by the Octopus and Humphrey perimetry instruments are based on measurements made
      under significantly different conditions, so the direct comparison of the indexes
      is not reliable. Nonetheless, empirically valid conversion formulas exist and can
      be used to compare the perimetric results for a patient tested with the two types
      of instrument.

PMID- 11244337
TI  - Reproducibility of nerve fiber layer thickness measurements using optical
      coherence tomography in silicone oil-filled eyes.
AB  - PURPOSE: To evaluate the reproducibility of nerve fiber layer (NFL) thickness
      measurements by optical coherence tomography (OCT) in individuals with silicone
      oil-filled eyes. METHODS: Eighteen patients who had undergone pars plana
      vitrectomy and silicone oil tamponade for retinal detachment were enrolled in a
      prospective, case-controlled clinical study. Each patient underwent OCT
      measurement of NFL thickness. Five repetitions of a series of scans on five
      separate occasions within a 0.5-month period were performed. Each eye was scanned
      at two different nerve head programs [radius (R) = 1.5 and R = 1.73]. The
      contralateral healthy eye was used as control. For each option (R = 1.5 and R =
      1.73) and region (superior, inferior, temporal, nasal and overall mean), variance
      components and intraclass correlation coefficients (ICCs) were determined using
      repeated-measures regression. In these models, NFL thickness, as measured by OCT,
      was considered to have three variance components: intersubject, intervisit
      (within subject, between dates), and intravisit (within subject, within date).
      The ICC (intersubject variance/total variance) was used as a measure of
      reliability. RESULTS: The contralateral healthy eye provided a higher degree of
      reproducibility than the silicone oil-filled eye (p = 0.0001). Reproducibility
      was higher in a given eye on a given visit than from visit to visit.
      Reproducibility as measured by ICCs was as follows: R = 1.5, 0.54/0.30 (control
      eyes/silicone oil-filled eyes); R = 1.73, 0.51/0.30. CONCLUSIONS: Reproducibility
      results for OCT measurement of NFL thickness are different in healthy eyes and
      silicone oil-filled eyes. NFL thickness measurement is not reliable in silicone
      oil-filled eyes.

PMID- 11244338
TI  - Eventual error caused by dehydration with pachometry.
AB  - Among the possible variables responsible for systemic errors in the acquisition
      of pachometric measurements, the corneal hydration condition plays a determinant
      role. In the present study, the authors have investigated the importance of this
      condition with two different pachometers (Storz Corneoscan II and Allergan
      Humphrey), reproducing an experimental dehydrated condition. The main datum
      arising from the comparison of the measurements obtained is represented by the
      different time course of the value of the measurement in the two groups. In fact,
      confronting the medium initial superimposed thickness value in the two tables
      (521 vs. 520 microm) there is a substantial difference in the final examination.
      For the first group of 60 corneas, the thickness values appear almost identical
      in the different intervals of time (medium initial thickness 521 vs. 512 microm
      final thickness). For the group examined with the solid-point machine, a
      decreasing thickness equal to 7% was evidenced (520 vs. 482 microm) with a
      significant decrease in the corneal thickness after only 45 s.

PMID- 11244339
TI  - Ocular Ferning test - effect of temperature and humidity on tear Ferning
      patterns.
AB  - BACKGROUND: The ocular ferning test is used as a diagnostic aid to evaluate
      patients with dry-eye disease. The ferning phenomenon is a dendritic growth form
      of dried tear fluid. The influence of temperature and relative humidity (rH) on
      the morphology of tear ferning patterns was investigated. METHODS: Two
      microliters of tear fluid of 5 volunteers with normal tear function were dropped
      onto a microscope slide with a pipette and were dried in a climatic chamber at
      four different temperatures (20, 22, 24 and 26 degrees C) and at four different
      grades of rH (30, 40, 50 and 60%) at each temperature. The dried droplet was
      divided according to distinct morphological features into a center, transition
      zone and margin. The center of the dried droplet was classified into four types
      according to the system of Rolando. RESULTS: In the temperature range between 20
      and 26 degrees C, rH has a strong influence on the ferning patterns. At these
      temperatures, increasing rH resulted in a deterioration of type I ferning
      obtained at 30% rH to type II or type III at 60% rH in all subjects. Otherwise,
      at rH of 30, 40 and 50%, no definite influence of temperature between 20 and 26
      degrees C was observed. At an rH of 60%, the ferning patterns changed with
      increasing temperature from 20 to 26 degrees C from type II to type III.
      CONCLUSION: High humidity can modify and deteriorate the ferning patterns of tear
      fluid from subjects with normal tear function. To obtain reproducible results
      using the ocular ferning test, stable conditions are necessary. An rH not higher
      than 50% at a temperature range between 20 and 26 degrees C produced ferning
      patterns without interstitial spaces which could be related to the best quality
      according to the system of Rolando.

PMID- 11244340
TI  - Comparative study of retinal nerve fiber layer loss in normal-tension glaucoma
      and chronic open-angle glaucoma.
AB  - PURPOSE: To clarify whether loss of the retinal nerve fiber layer in normal
      tension glaucoma (NTG) differs from that in chronic open-angle glaucoma (COAG).
      METHODS: Using a scanning laser polarimeter, retinal nerve fiber layer thickness
      (RNFLT) was measured in 21 patients with NTG, 21 patients with COAG and 21 normal
      controls. The three groups were matched for age, and the NTG and COAG groups were
      matched for visual field loss. RESULTS: The mean RNFLT was significantly less in
      the NTG than in the control group and less in the COAG than in the controls and
      NTG group. Although the correlations between the parameters of RNFLT and
      homotopic visual field measurements were significant in COAG, none of the
      correlations were significant in NTG. CONCLUSIONS: The present results suggest
      that loss of the retinal nerve fiber layer in NTG differs from that in COAG.

PMID- 11244341
TI  - Elevated nitric oxide level in aqueous humor of patients with acute angle-closure
      glaucoma.
AB  - Nitric oxide, a noxious and free-radical gas, plays a key role in vasodilatation,
      inflammation, immunity, and neurotoxicity. Studies have shown that a recently
      detected NO synthase inducible isoform, found in astrocytes in the optic nerve
      heads of glaucoma patients, could stimulate excessive production of NO. The
      purpose of our study was to elucidate the role of NO production in the
      pathogenesis of glaucoma. We measured the concentrations of NO in aqueous humor
      from 11 patients with acute angle-closure glaucoma (AACG) and 14 patients with
      cataract. All samples were collected from patients who were free of any other
      systemic disease. Utilizing a chemiluminescence assay, we found that in AACG
      patients the NO levels in aqueous humor samples (83.2 +/- 6.7 microM) were
      significantly higher than in cataract patients (27.1 +/- 3.6 microM; p < 0.001).
      We therefore concluded that excessive NO in AACG patients reflects the degree of
      ocular impairment demonstrated by concomitant retinal cell and optic nerve cell
      damage.

PMID- 11244342
TI  - Type a syndrome of insulin resistance: anterior chamber anomalies of the eye and
      effects of insulin-like growth factor-I on the retina.
AB  - BACKGROUND: The purpose of this work was to describe the anterior chamber and
      iris anomalies as well as to evaluate the effects of recombinant human insulin
      like growth factor-I (rhIGF-I) on the retinal vessels in 2 diabetic patients with
      type A syndrome of insulin resistance, a rare condition associated with
      acanthosis nigricans. METHODS: Ophthalmologic examinations, including photographs
      and fluorescein angiograms, were performed before, and 2 and 4 weeks after
      starting subcutaneous rhIGF-I treatment, and 3 months after withdrawal of rhIGF-I
      treatment. RESULTS: Both patients had goniodysgenesis with mild elevation of the
      intraocular pressure. Before and after 2 weeks of treatment with rhIGF-I, the
      fundus and the fluorescein angiograms were mainly normal. After 4 weeks of rhIGF
      I treatment both patients' retinas revealed leakage of fluorescein. Three (case
      1) and 4 months (case 2) after withdrawal of rhIGF-I, the fundus of all four eyes
      were again without leakage. CONCLUSIONS: The anterior chamber anomalies found in
      these patients may be part of the type A syndrome of insulin resistance and could
      alert clinicians that these patients might not have the usual type of diabetes.
      Moreover, the data show that exogenous rhIGF-I administration in patients with
      type A syndrome of insulin resistance alters the permeability of the superficial
      layer of retinal capillaries which is comparable to the earliest angiographic
      changes in childhood diabetic retinopathy. Whether this is a direct effect of
      rhIGF-I, as suggested by experiments in an animal model, or an indirect effect
      due to the near-normalization of the glucose levels by rhIGF-I warrants further
      investigations. Finally, this work points to an important caveat regarding the
      therapeutic use of rhIGF-I in this patient population.

PMID- 11244343
TI  - Comparison of hypotonic and isotonic solutions containing sodium hyaluronate on
      the symptomatic treatment of dry eye patients.
AB  - This study was designed to compare the efficacy of two artificial tears both
      containing hyaluronic acid but differing in their osmolarity. A multicentric
      double-masked, crossover clinical trial was performed in which 158 subjects were
      randomized to receive either hypotonic or isotonic artificial tears up to 6 times
      a day. Both treatments were effective in improving signs and symptoms to a
      similar extent. No adverse events were reported. It was concluded that hypotonic
      and isotonic eye drops are comparable for the symptomatic treatment of patients
      suffering from dry eye syndrome.

PMID- 11244344
TI  - Central retinal vein occlusion and nonarteritic ischemic optic neuropathy in 2
      patients with mild iron deficiency anemia.
AB  - We report on 2 patients with ophthalmologic complications associated with mild
      iron deficiency anemia. Case 1, a 37-year-old female patient, presented after 4
      days of blurred vision in her left eye. Ophthalmoscopic and angiographic findings
      were consistent with the diagnosis of central retinal vein occlusion (CRVO).
      Further hematologic investigation into possible causes disclosed mild iron
      deficiency anemia (Hb 9.4 g/dl, hematocrit 30.5%). After the patient's visual
      acuity had worsened progressively to 20/50, an initial thrombolytic treatment and
      continuous intravenous heparinization was started on day 8, followed by oral
      substitution therapy with ferrous sulfate. On day 14, her visual acuity recovered
      to 20/20 OS and remained stable during follow-up. Case 2, a 50-year-old female
      patient, presented with a 1-week-history of blurred vision and metamorphopsia.
      Her visual acuity was 20/200. Further examination revealed a nonarteritic
      ischemic optic neuropathy and an iron deficiency anemia as the underlying disease
      (Hb 7.3 g/dl, hematocrit 25%). Despite intravenous heparinization and systemic
      treatment with steroids, there was no improvement in visual acuity. Clinicians
      involved in the management of chronic iron deficiency anemia should be aware of
      possible ophthalmic manifestations in this disease.

PMID- 11244345
TI  - Coats' disease and congenital retinoschisis in a single eye: a case report and
      DNA analysis.
AB  - The clinical features of Coats' disease and congenital retinoschisis (RS) are
      distinctly different. Therefore, finding changes consistent with Coats' disease
      and congenital RS in a single eye is an unusual occurrence. The following report
      describes two cases with a Coats' telangiectatic lesion in one region of the
      retina separated by normal retina and the presence of central and peripheral
      congenital RS. Molecular genetic analysis of the Norrie disease and RS genes
      failed to identify disease-causing or polymorphic mutations in either of the
      genes, suggesting that the above condition is clinically and genetically a
      different disorder. Further studies are needed to identify the genes responsible
      for the above disorder and associated ocular manifestations.

PMID- 11244346
TI  - Breast carcinoma metastatic to the eyelid presenting as the first sign of
      insufficient chemotherapy.
AB  - Metastatic eyelid tumors are uncommon. Their presentation may vary markedly. We
      describe a 61-year-old female who presented with a tender nodule in her right
      upper eyelid shortly after chemotherapy for metastatic disease. She had undergone
      right mastectomy and radiotherapy because of an adenocarcinoma 16 years ago.
      Histopathologic findings were consistent with metastatic carcinoma. Knowledge of
      the diverse clinical and histopathologic features of metastatic breast carcinoma
      to the eyelids is essential for the appropriate management of these patients.
      Breast carcinoma metastatic to the eyelid represented in this patient the only
      sign of insufficient chemotherapy.

PMID- 11244347
TI  - The terminology of eye injuries.

PMID- 11244348
TI  - Optical coherence tomography in spontaneously resolving vitreomacular traction
      syndrome.

PMID- 11244349
TI  - Vacuoles in the Acrysof intraocular lens as factor of the presence of serum in
      aqueous humor.
AB  - OBJECTIVE: Acrysoftrade mark (Alcon) foldable lenses (IOLs) have been shown to be
      highly biocompatible and exhibit a low incidence of posterior capsular
      opacification. However, minute vacuoles or 'glistenings' have been observed in
      some Acrysof IOLs. The clinical relevance of vacuole formation is presently
      unclear. To help clarify the influence of factors present under in vivo
      conditions on vacuole formation, the present experimental study examines the
      influence of aqueous humor components on the occurrence of vacuoles in Acrysof
      IOLs. METHODS: A total of 12 sterile Acrysof IOLs (Alcon, MA60BM) were incubated
      at body temperature (37 degrees C) for 3 or 6 months in anterior-chamber aqueous
      humor with or without human serum. The center portion was cut from two
      unconditioned, unhydrated, sterile control IOLs and the 12 conditioned IOLs and
      examined using light microscopy for vacuole formation. A third unconditioned,
      hydrated control IOL was examined using light and scanning electron microscopy.
      MEASURES: The incidence of vacuoles was quantified by two independent
      investigators using light microscopy. After hydration with balanced salt
      solution, the surface quality of a control IOL was examined using scanning
      electron microscopy. RESULTS: The control IOLs exhibited no or very few vacuoles.
      Scanning electron microscopy revealed that the control IOLs had normal surface
      texture without any surface vacuoles. IOLs that had been conditioned in aqueous
      humor without serum exhibited no great increase in the number of vacuoles,
      whereas IOLs conditioned in aqueous humor with serum exhibited a greater number
      of vacuoles that increased over time. CONCLUSIONS: The number of vacuoles
      increases with incubation time in aqueous humor containing serum. The addition of
      serum increased the proportion of lipids and proteins in the solution, which also
      occurs with a breakdown in the blood-aqueous barrier. The results of the present
      study point to a physiological factor that may lead to vacuole formation in IOLs
      and may aid clinicians in identifying risk factors involved in the formation of
      vacuoles.

PMID- 11244350
TI  - Metabolic changes in rabbit lens induced by treatment with dexamethasone.
AB  - Metabolic changes in the rabbit lens have been studied by means of nuclear
      magnetic resonance spectroscopy. These changes have been induced by prolonged
      topical treatment with dexamethasone. Our results demonstrate an increase in
      sorbitol, sorbitol-3-phosphate, fructose-3-phosphate, glycerol-3-phosphate and
      glucose-6-phosphate levels and a decrease in glutathione sulphate (GSH) and myo
      inositol levels, in agreement with what was observed in lenses from streptozocin
      diabetic rats before lens opacity. The hyperglycaemia can only partially explain
      all these observed biochemical variations. The lack of increase in the
      intermediates of pentose cycle, such as sedoheptulose-7-phosphate, seems to
      support the hypothesis of an inhibition of glucose-6-phosphate dehydrogenase by
      dexamethasone treatment. Finally dexamethasone treatment induces a decrease in
      GSH. The decreasing or the loss of GSH has been suggested as a possible
      pathogenic mechanism in the cataract formation.

PMID- 11244351
TI  - Effect of a nitric oxide synthase inhibitor on lens-induced myopia.
AB  - PURPOSE: It has still not been determined whether the retinal mechanism causing
      form-deprivation myopia (FDM) is different from that causing lens-induced myopia
      (LIM). We previously reported that FDM was blocked by an intravitreal injection
      of the nitric oxide (NO) synthase inhibitor, N-nitro-L-arginine methyl ester (L
      NAME). In this study, we investigated the effect of L-NAME on LIM in chicks.
      METHOD: The left eyes of 6-day-old chicks were injected with 30 microl of
      nontoxic concentrations of L-NAME (< or = 360 mM) or saline. The right eyes were
      injected with 30 microl of saline. A -16 dpt lens was placed in front of the left
      eye for 6 days. Another group of 6 chicks were injected with 180 mM L-NAME (left
      eye) and with saline (right eye) before placing -16 dpt lenses in front of both
      eyes. After removing the lens, the refraction and the axial length were measured.
      The effect of L-NAME (180 mM) on the retina of a separate group of chicks was
      examined by electroretinography 60 min after an intravitreal injection in non-LIM
      treated eyes. RESULTS: The eyes of chicks that were injected with 180 or 360 mM L
      NAME were less myopic and had significantly shorter axial lengths than control
      eyes. A significant decrease of the On response and an increase of the Off
      response were observed. CONCLUSION: The injection of L-NAME into developing chick
      eyes that were then covered with a -16 dpt lens resulted in a modifications of
      retinal function and an inhibition of the development of myopia. These results,
      combined with the earlier findings, suggest that NO modulates a common retinal
      pathway that leads to both LIM and FDM.

PMID- 11244352
TI  - Epitheliomesenchymal transdifferentiation of cultured RPE cells.
AB  - Retinal pigment epithelium (RPE) cells of the proliferative vitreoretinopathy
      (PVR) membrane take on the shape of fibroblasts and participate in fibrosis, thus
      deviating from the character of epithelial cells. This study was undertaken to
      evaluate RPE cell transdifferentiation in vitro. During the culture of porcine
      RPE cells, primary and 10th-passaged RPE cells were investigated for cell growth
      in response to transforming growth factor (TGF) beta(2), change of phenotype and
      amount in collagen synthesis as well as expression of alpha-smooth-muscle actin
      (alpha-SMA). TGF-beta(2) inhibited the proliferation of the primary cultures of
      RPE cells in a dose-dependent manner, while the spindle-shaped 10th-passaged RPE
      cells were not inhibited by TGF-beta(2). The 10th-subcultured cells did not show
      much difference in the quality of collagen synthesis, other than type VIII
      collagen which was not produced. Collagen synthesis was dose-dependently
      stimulated by TGF-beta(2). The stimulation by TGF-beta(2) in the 10th-passaged
      RPE cells was much greater than in primary RPE cells. The 10th-subcultured RPE
      cells produced substantial alpha-SMA compared to alpha-SMA production by primary
      RPE cells. These results were also observed by confocal laser microscopy. These
      findings indicated that RPE metaplasia resulting in a change of biological cell
      behavior might be a necessary predisposing step in the development of PVR.

PMID- 11244353
TI  - Antisilicone antibodies in patients with silicone implants for retinal detachment
      surgery.
AB  - A modified ELISA assay was used to detect IgG binding to silicone and IgG
      subtypes in serum of patients bearing silicone bands, silicone sponges and
      intraocular silicone oil. Presence of autoantibodies (rheumatoid factor,
      antinuclear antibody, and SCL 70) and signs and symptoms of autoimmune diseases
      were also checked. Antisilicone antibodies were detected in 35.7% of patients
      with solid silicone and in 83% in those with silicone oil. This increase in IgG
      is mainly due to IgG1. Nevertheless no positive results were found in detecting
      signs and symptoms of autoimmune diseases.

PMID- 11244354
TI  - Facilitatory and neurotoxic effects of intravitreal ornithine on the
      electroretinographic responses of albino rats.
AB  - The effect of an intravitreal injection of ornithine on the retina of rats was
      studied electroretinographically. Rats were injected intravitreally with 5 microl
      of 0.02, 0.25 and 0.5 M ornithine. Electroretinograms (ERGs) were recorded
      before, and 1, 3 and 9 days after the injection. High doses of ornithine (0.5 M)
      reduced while low doses (0.02 M) enhanced the ERG amplitudes. The implicit time
      of the a-wave was delayed at all concentrations after ornithine injection, which
      suggests that implicit times may be a more sensitive parameter of the ornithine
      effect. There were significant changes in the stimulus intensity necessary to
      obtain the one half of the maximum amplitude of the b-wave that may have been
      caused by damage of the photoreceptors and retinal pigment epithelium cells by
      ornithine. We conclude that the effect of ornithine on retinal function is dose
      dependent and can either enhance or depress the ERG amplitudes.

PMID- 11244355
TI  - TIMP-1 production by human scleral fibroblast decreases in response to cyclic
      mechanical stretching.
AB  - PURPOSE: The effect of mechanical stretching was examined on cultured scleral
      fibroblasts of the human eye in order to observe changes in their production of
      TIMP (tissue inhibitor of metalloproteinase)-1, MMP (matrix metalloproteinase)-1
      and -2 in response to physiological strain. METHODS: Human scleral fibroblasts
      were cultured from scleral tissue resected during foveal translocation surgery.
      The fibroblasts in near confluency were exposed to mechanical stretching of the
      bottom of a 6-cm Petri dish at the maximum magnitude of 4500 microstrain and at a
      cycle of 30 s for 72 h. TIMP-1, MMP-1 and MMP-2 levels in the medium following
      24, 48 and 72 h of cyclic stretching were measured by enzyme immunoassay.
      RESULTS: The growth of scleral fibroblasts during the 72-hour period of
      stretching did not show a significant difference from that of non-stretched
      control fibroblasts. Scleral fibroblasts in the stretched group produced a
      significantly smaller amount of TIMP-1 at 72 h after stretching, compared with
      nonstretched control (p = 0.0353, Student t-test). The levels of MMP-1 and MMP-2
      produced by scleral fibroblasts were not significantly different between the
      stretched group and nonstretched group. CONCLUSION: The production of TIMP-1 by
      human scleral fibroblasts was suppressed by cyclic mechanical stretching.
      Mechanical strain would be one factor to regulate the homeostasis of
      extracellular matrix in the sclera.

PMID- 11244356
TI  - Short-time application of latanoprost does not stimulate melanogenesis in bovine
      ocular melanin-containing cells in vitro.
AB  - Topical use of latanoprost for glaucoma can lead to an increase in iris and eye
      lash pigmentation but the precise mechanism is unclear. To study the possible
      effect of this drug on ocular melanogenesis, we used cultures of bovine iris
      melanocytes, iris pigment epithelial cells, retinal pigment epithelial cells, and
      choroidal melanocytes. Latanoprost (at concentrations of 10(-8) and 10(-6) mol)
      was applied for 3 days, and cell numbers as well as melanin content were measured
      prior to and 10 days after exposure and compared to untreated controls. In none
      of the cell types examined a significant increase in melanin content or an
      increase in cell proliferation was observed. Additional treatment with the
      tyrosinase inhibitor alpha-methyl-p-tyrosine showed no significant effect either.
      Our results support the concept of a rather complex mechanism underlying the
      increased iris pigmentation after treatment with latanoprost.

PMID- 11244357
TI  - Evidence for intraocular synthesis of kynurenic acid, a putative endogenous
      neuroprotectant.
AB  - Kynurenic acid (KYNA), an excitatory amino acid antagonist preferentially active
      at glycine binding site of the NMDA receptor, has been previously identified in
      the brain. This study was designed to examine its presence in the rabbit vitreous
      humor. Mean (+/- SD) level of KYNA in the vitreous was 22.3 +/- 3.9 pmol/ml as
      determined by HPLC. Intravitreal administration of 10 mmol aminooxyacetic acid
      (AOAA), a KYNA synthesis inhibitor, diminished its production by 9.6% after 2 h,
      47.8% after 24 h and 21.5% after 48 h. It can be concluded that AOAA decreases
      the intravitreal concentration of KYNA, providing evidence of its intraocular
      origin.

PMID- 11244358
TI  - Inhibitory effect of 2'-O-benzoylcinnamaldehyde on vascular endothelial cell
      proliferation and migration.
AB  - PURPOSE: To evaluate the inhibitory effect of the farnesyl transferase inhibitor
      2'-O-benzoylcinnamaldehyde (CB 2'-ph) on proliferation and migration of vascular
      endothelial cells. METHODS: Bovine lens epithelial cells, bovine corneal
      endothelial cells, bovine keratocytes, bovine aortic endothelial cells (BAECs)
      and human umbilical vein endothelial cells (HUVECs) were treated with CB 2'-ph to
      determine its cell type specificity and antiproliferative effect. For inhibition
      of vascular endothelial cell growth factor (VEGF)- or basic fibroblast growth
      factor (bFGF)-induced proliferation of HUVECs, these cells were treated with
      various concentrations of CB 2'-ph. To assess the proliferation, MTT (3-[4,5
      dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay was used. The
      migration assay was also performed to determine the effect of CB 2'-ph on HUVECs.
      The distance of HUVEC outgrowth was measured from the scraped edge of a monolayer
      after treatment with CB 2'-ph concentrations of 0, 1.5 and 2.5 microg/ml for 24,
      48 and 72 h. RESULTS: The CB 2'-ph had an inhibitory effect on all tested types
      of cell proliferation but only HUVEC and BAEC proliferation was specifically
      inhibited in a dose-dependent manner. In addition, CB 2'-ph inhibited VEGF- or
      bFGF-induced proliferation and migration of HUVECs in a dose-dependent manner.
      CONCLUSIONS: These results indicate that CB 2'-ph, a farnesyl transferase
      inhibitor is thought to be an effective inhibitor of vascular endothelial cell
      proliferation and migration.

PMID- 11244359
TI  - In vitro susceptibilities to topical antibiotics of bacteria isolated from the
      surface of clinically symptomatic eyes.
AB  - BACKGROUND: The permanent change of resistance patterns of bacteria causing
      ocular infections makes repeat susceptibility testings against the most recent
      clinical isolates mandatory. The aim of the present study was to assess the in
      vitro susceptibility of ocular bacterial isolates of clinically symptomatic eyes
      admitted to the outpatient clinic of the eye department of a large central
      hospital to commonly used topical antibiotics. METHODS: Ocular isolates (n = 454)
      were tested for their susceptibility to ofloxacin, ciprofloxacin, norfloxacin,
      gentamicin, tobramycin, meomycin, bacitracin, erythromycin, tetracycline and
      chloramphenicol. RESULTS: All three tested fluoroquinolones were found to be very
      effective against gram-negative organisms but demonstrated some weakness against
      certain strains of gram-positive germs, in particular coagulase-negative
      staphylococci and Streptococcus viridans. These germs, however, were very
      susceptible to bacitracin and chloramphenicol. The relative overall in vitro
      efficacy was (in decreasing order): chloramphenicol, ciprofloxacin, ofloxacin,
      norfloxacin, bacitracin, tetracycline, neomycin, erythromycin, tobramycin and
      gentamicin. CONCLUSION: Chloramphenicol had the highest overall in vitro
      efficacy, but has potential lethal side effects. The fluoroquinolones were highly
      effective, especially being superior to the aminoglycosides tested, but no single
      antibiotic provided 100% coverage against all of the bacterial isolates that were
      tested.

PMID- 11244361
TI  - ARM--a new disease or a new discovery? Comments on the article by E.L.
      Altschuler.

PMID- 11244360
TI  - Is age-related macular degeneration a new disease?

PMID- 11244362
TI  - Surgical management of the neck in thyroid cancer.
AB  - Thyroid cancer is a relatively common clinical problem. The American Cancer
      Society has estimated 1,050,000 newly diagnosed cancers in 1999 in the United
      States, of which 16,000 are expected to be of thyroid origin. Although most
      thyroid cancers have an excellent prognosis as compared with other malignant
      tumors, it is estimated that approximately 1,225 deaths will be attributed to the
      disease [1].

PMID- 11244363
TI  - Cortical transcranial magnetic stimulation of the frontalis muscle:
      characteristic features and details on motor-evoked potentials of the forehead.
AB  - The effect of coil position on the head surface along the interaural line on
      motor-evoked potentials (MEPs) of the frontalis muscle due to cortical
      transcranial magnetic stimulation was investigated in 16 healthy subjects.
      Bilateral reproducible responses could be observed in all subjects investigated
      at coil positions varying from 2 to 12 cm lateral to the vertex. MEP amplitudes
      of the frontalis muscle offered no significant side differences neither in
      amplitude nor in onset latency. Despite a considerable overlap, a statistically
      significant separation (p < 0.0001) of the two areas from which reproducible MEPs
      of upper and lower mimetic muscles could be elicited was evident for the
      calculated mediolateral center with the frontalis muscle area being placed more
      medially. Our findings are in accordance with anatomical studies indicating a
      predominance of corticonuclear descending fibers to lower but not to upper facial
      motoneurons.

PMID- 11244364
TI  - Decreased trigeminal sensitivity in anosmia.
AB  - The present study aimed to investigate intranasal trigeminal sensitivity in a
      large sample of patients with anosmia due to different etiologies. We
      investigated the trigeminal detection threshold for formic acid in healthy
      controls (n = 96) and patients with anosmia due to head trauma (n = 18) or
      sinonasal disease (n = 54). Anosmics exhibited higher thresholds compared with
      normosmics (p < 0.001). In addition, thresholds were found to be higher in
      patients with posttraumatic anosmia compared to anosmics with sinonasal disease
      (p < 0.001). The data indicate that (1) loss of olfactory sensitivity in humans
      may be associated with a decreased sensitivity towards trigeminal stimuli and (2)
      alteration of intranasal trigeminal function is stronger in patients with
      posttraumatic anosmia compared to patients with sinonasal disease. This may have
      implications for the medicolegal investigation of anosmic patients where
      trigeminal stimuli are frequently used to assess the patient's response bias.

PMID- 11244366
TI  - Expression of the voltage-dependent chloride channel ClC-3 in human nasal tissue.
AB  - In the present study, ClC-3, one of the voltage-dependent chloride channels, was
      identified in human nasal tissue. In situ hybridization and immunohistochemical
      investigations demonstrated the localization of ClC-3 in the serous acini and
      ductal portions of submucosal nasal glands, which are the primary source of nasal
      secretion. Our data suggest that this channel contributes to nasal secretion via
      chloride transport. Its dysfunction might lead to abnormal nasal secretion in
      such pathological states as sinusitis.

PMID- 11244365
TI  - Vasomotor rhinitis: clinical efficacy of azelastine nasal spray in comparison
      with placebo.
AB  - The H(1) antagonist azelastine is used in nasal sprays for the treatment of
      allergic rhinitis, but its therapeutic efficacy in vasomotor rhinitis is unknown.
      We performed a multicenter randomized double-blind placebo-controlled study of
      the efficacy and tolerance of azelastine nasal spray in 89 adult patients with
      vasomotor rhinitis (confirmed by negative Phadiatop). Following a washout period,
      patients were treated for 15 days with one puff three times daily per nostril of
      azelastine (n = 44) or placebo (n = 45) nasal spray. Efficacy was evaluated by
      the reduction in symptomatology and by rhinoscopy. Intent-to-treat analysis
      revealed better results in the azelastine group for all assessed symptoms; the
      significance level was reached for nasal obstruction on day 15 (p = 0.042). Using
      per protocol analysis (in 85 patients complying with the protocol), the
      significance level was reached for nasal obstruction on day 15 (p = 0.017) and
      for the percentage of success in rhinorrhea (p = 0.023). In the azelastine group,
      rhinoscopy examination showed a significantly higher reduction in the
      inflammatory level and edema of the nasal mucosa (p = 0.03 and 0.02 for VAS on
      day 15 respectively, per protocol analysis). General efficacy assessment by the
      physician and the patient was in favor of azelastine (with significance levels
      <0.01). No drowsiness or serious adverse event was reported, and the frequency of
      mouth dryness and headaches was similar in the two treatment groups. The present
      study demonstrates the efficacy of azelastine nasal spray in the treatment of
      vasomotor rhinitis. The best achieved results were a decrease in nasal
      obstruction and mucosal edema. Further studies are required to investigate if
      this therapeutic benefit results from H(1) antagonism or from another, not well
      characterized pharmacological action of azelastine.

PMID- 11244367
TI  - Possibility of reciprocal infection of methicillin-resistant Staphylococcus
      aureus between medical personnel and patients undergoing middle ear surgery.
AB  - The incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection
      after middle ear surgery has recently increased in our hospital. In this study we
      tried to determine whether the strains of MRSA isolated from infected patients
      are identical to those obtained from medical personnel, to prove a reciprocal
      transmission between medical personnel and patients. Surveillance bacterial
      cultures of medical personnel were performed from the anterior nares and from the
      fingertip. Molecular epidemiological studies, ribotyping and pulsed-field gel
      electrophoresis (PFGE) were used to compare the 12 MRSA strains obtained from
      carriers among medical personnel with the 60 strains identified from patient's
      otorrhea. Six different MRSA strains were identified from ribotyping, and three
      subtypes from PFGE. There was a particular subtype which was the most frequently
      identified strain found in both medical carriers and patients. Postoperative MRSA
      infection rates after the treatment of medical carriers and application of
      preventive procedures decreased from 11.9 to 5.7%. These findings suggest that
      the MRSA transmissions have occurred between medical personnel and patients.

PMID- 11244368
TI  - Evaluation of a new method for assessing symptoms.
AB  - BACKGROUND: Many studies in rhinology are based on results from symptom scoring.
      Numerous methods are used to estimate symptoms. With some of them the patients
      choose between various alternatives for estimating the severity of their
      symptoms, but the commonest method is the visual analogue scale (VAS), which is
      regarded as reliable. METHODS: In this study, we evaluate a new method for
      assessing symptoms, with which the patient uses the telephone to call a computer.
      We compare the results using the new method with those using symptoms estimation
      with VAS. RESULTS: The results are based on 487 observations in patients with
      birch pollen allergic rhinitis in the pollen season. A high correlation was found
      between the results using the new method and those using the VAS. In a
      questionnaire, the patients answered questions concerning the two methods. Most
      patients preferred the new telephone method. They found it easier to estimate
      their symptoms properly and easier to perform. CONCLUSION: We conclude that
      telephone scoring of symptoms is a reliable and adequate method when symptom
      scoring is used as hard data in a study.

PMID- 11244369
TI  - Viral co-infection does not reduce the efficacy of vaccination against non
      typeable Haemophilus influenzae middle ear infection in a rat model.
AB  - The mucosal vaccination of rodents with killed non-typeable Haemophilus
      influenzae (NTHi) has been previously shown to enhance live NTHi clearance
      following middle ear challenge. This study assessed the efficacy of mucosal anti
      NTHi vaccination during a concomitant viral infection of the respiratory tract.
      Animals were mucosally immunised with killed NTHi by intra-Peyer's patch primary
      inoculation and lung (intratracheal) boost. At the time of both immunisations
      rats were also infected intra-nasally with Sendai virus. Concomitant Sendai virus
      infection did not influence the efficacy of anti-NTHi vaccination mediated
      clearance of NTHi from the middle ear. This would suggest that immunisation
      strategies to prevent bacterial middle ear infection would be effective despite
      the presence of concomitant viral agents.

PMID- 11244370
TI  - Dislocation of the incus into the external auditory canal after mountain-biking
      accident.
AB  - We report a rare case of incus dislocation to the external auditory canal after a
      mountain-biking accident. Otoscopy showed ossicular protrusion in the upper part
      of the left external auditory canal. CT indicated the disappearance of the incus,
      and an incus-like bone was found in the left external auditory canal. There was
      another bony and board-like structure in the attic. During the surgery, a square
      shaped bony plate (1 x 1 cm) was found in the attic. It was determined that the
      bony plate had fallen from the tegmen of the attic. The fracture line in the
      posterosuperior auditory canal extending to the fossa incudis was identified.
      According to these findings, it was considered that the incus was pushed into the
      external auditory canal by the impact of skull injury through the fractured
      posterosuperior auditory canal, which opened widely enough for incus dislocation.

PMID- 11244372
TI  - Primary chondrosarcoma arising in the parotid gland.
AB  - We report an extremely rare case of chondrosarcoma arising in the left parotid
      gland in a 45-year-old man who complained of painless swelling of the
      postauricular region. Computed tomography revealed a well-circumscribed tumor in
      the parotid area with a rim of scattered calcification. Under the diagnosis of
      benign parotid tumor, the tumor mass was removed with adequate margin. Histologic
      features were consistent with a low-grade chondrosarcoma showing lobular growth
      but clearly separated from adjacent glandular tissue of the parotid gland. Entire
      examination of the tumor disclosed no component of pleomorphic adenoma. There has
      been no evidence of recurrence for 2 months after the operation. The current case
      indicates that the parotid gland could be the site of occurrence of de novo
      primary chondrosarcoma.

PMID- 11244371
TI  - Endonasal endoscopic dacryocystorhinostomy in a four-month-old infant.
AB  - The authors present a case of endonasal endoscopic dacryocystorhinostomy in a 4
      month-old girl suffering from remarkable epiphora, persistent bulging and
      recurrent abscesses in the medial canthal region of the left eye. All
      conservative therapeutic attempts failed. Several external incisions were
      performed in order to solve the acute phases of the inflamed lacrimal sac. The
      procedure was performed by means of otologic microsurgical instruments under
      endoscopic control. No silicone stent was used. Ten months after surgery, the
      girl is doing very well.

PMID- 11244373
TI  - Chondroid chordoma of the lateral skull base.
AB  - A rare case of chondroid chordoma of the lateral skull base with laterocervical
      extension is reported. Clinical, radiological and pathological features of the
      tumor are described. This unusual location of chondroid chordoma enabled total
      resection of the neoplastic tissue through a combined laterocervical and far
      lateral transjugular approach.

PMID- 11244374
TI  - A rare tumor of salivary gland origin: hyalinizing clear cell carcinoma.

PMID- 11244375
TI  - Depressive symptoms and academic self-image in adolescence.
AB  - The aim of this paper was to specifically analyse the relationship between the
      different components of academic self-image, defined as the way adolescents
      represent themselves as students, and self-reported depressive symptoms, assessed
      with the Children's Depression Inventory (CDI), in a non-clinical sample of 298
      adolescents. We considered both adolescents' beliefs about their own cognitive
      functioning in academic performance and beliefs about their emotional attitude in
      achievement situations. Our data indicate that the pattern of correlation between
      emotional beliefs about schooling and learning are significantly related to CDI
      scores, but this correlation is not evident for the cognitive beliefs. This
      pattern of correlation is affected by actual school functioning, because
      correlation between CDI and beliefs is much more significant in subjects without
      school failure. Differences between gender in CDI scores, beliefs about schooling
      and learning, and pattern of correlation are considered. These results can enable
      to focus supporting psychological interventions on more specific targets.

PMID- 11244376
TI  - Insight and resistance in patients with obsessive-compulsive disorder.
AB  - The aim of this study was to evaluate the degree of insight and resistance in a
      sample of obsessive-compulsive patients, and the predictive value of poor insight
      with respect to response to treatment with serotonin reuptake inhibitors (SRIs).
      Ninety-three patients fulfilling DSM-IV criteria for obsessive-compulsive
      disorder were evaluated. Seventy patients were treated with an SRI in a 24-week
      open-label trial. Sixteen percent of the patients did not recognize obsessions
      and compulsions as unreasonable or senseless. Fifty-two percent of the patients
      did not try to resist, 72% had little or no control over obsessions, and 64% were
      not able to exercise an effective control over compulsions. Patients with poor
      insight had a greater severity of obsessive-compulsive symptoms, a higher rate of
      schizophrenia spectrum disorders in their first-degree relatives and a higher
      frequency of a history of psychiatric disorders during childhood. Fifty-two
      percent of the patients with normal insight responded to SRIs, whereas none of
      the patients with poor insight were found to be responders. These results suggest
      the utility of the assessment of insight and resistance in obsessive-compulsive
      patients, also for the prediction of response to treatment with SRIs.

PMID- 11244377
TI  - Evaluation of the multiaxial system of ICD-10 (preliminary praft): correlations
      between multiaxial assessment and clinical judgements of aetiology, treatment
      indication and prognosis.
AB  - Forty-five raters in 7 German centres took part in a multicentric field trial of
      the multiaxial system of ICD-10, delivering a total of 488 multiaxial assessments
      of 12 written case summaries. In addition to the multi-axial ratings (including
      main and subsidiary psychiatry diagnoses, level of social dysfunctioning and
      psychosocial stressors), assessments were made by the raters of the aetiology,
      treatment indications and prognosis of the main psychiatric disorder. There were
      significant correlations between these judgements and the measures of the
      multiaxial ratings: 62% of the cases diagnosed as endogenous were assessed as
      having a high level of social dysfunctioning (the proportion for all cases being
      50.4%) and 63.4% as having a low number of stressors (vs. 52.8% in all cases). In
      contrast, cases diagnosed as reactive were assessed as having a lower level of
      social dysfunctioning and more social stressors. Cases whose prognosis was poor
      showed a higher rate of comorbidity and a high level of social dysfunctioning.
      The results demonstrate that the multiaxial approach reflects factors important
      to the process of clinical treatment and decision making and delivers preliminary
      evidence of this system's treatment and prognostic validity.

PMID- 11244378
TI  - Lateralized direct and indirect semantic priming effects in subjects with
      paranormal experiences and beliefs.
AB  - The present investigation tested the hypothesis that, as an aspect of schizotypal
      thinking, the formation of paranormal beliefs was related to spreading activation
      characteristics within semantic networks. From a larger student population (n =
      117) prescreened for paranormal belief, 12 strong believers and 12 strong
      disbelievers (all women) were invited for a lateralized semantic priming task
      with directly and indirectly related prime-target pairs. Believers showed
      stronger indirect (but not direct) semantic priming effects than disbelievers
      after left (but not right) visual field stimulation, indicating faster
      appreciation of distant semantic relations specifically by the right hemisphere,
      reportedly specialized in coarse rather than focused semantic processing. These
      results are discussed in the light of recent findings in schizophrenic patients
      with thought disorders. They suggest that a disinhibition with semantic networks
      may underlie the formation of paranormal belief. The potential usefulness of work
      with healthy subjects for neuropsychiatric research is stressed.

PMID- 11244379
TI  - The clinical picture of bipolar II outpatient depression in private practice.
AB  - Uncertainties exist about whether depressive episodes differ phenomenologically
      in unipolar and bipolar II patients. The aim of the present study was to better
      define the clinical picture and course of bipolar II depression. Three hundred
      and ninety-nine consecutive outpatients, presenting for treatment of unipolar and
      bipolar II depression, were interviewed with the Structured Clinical Interview
      for DSM-IV, the Montgomery-Asberg Depression Rating Scale and the Global
      Assessment of Functioning Scale. Bipolar II depression had significantly lower
      age at onset, more recurrences and more patients with DSM-IV atypical features.
      Gender, duration of illness, psychosis, chronicity, severity, axis I comorbidity,
      melancholic features, individual atypical symptoms and other symptoms of
      depression were not significantly different. The presence of DSM-IV atypical
      features predicted bipolar II diagnosis with 63% probability.

PMID- 11244380
TI  - Social cognition and psychopathology in an evolutionary perspective. Current
      status and proposals for research.
AB  - The phylogenetic and ontogenetic developments of social cognition have been a
      major research focus of evolutionary and developmental psychology. Theory of mind
      or so-called Machiavellian intelligence, that is the capacity to infer mental
      states of other individuals and to manipulate them in order to maximise social
      success, probably emerged due to the need to cope with an increasingly complex
      social environment. Studies on social reasoning suggest disturbances of mental
      state attribution in psychiatric disorders. However, apart from autism spectrum
      disorders, the systematic evaluation of social cognition is still in its infancy,
      and the present data are ambiguous due to methodological difficulties. Based on
      the concept of the modular organisation of the mind, a stepwise investigation of
      social cognition in psychiatric disorders is proposed, including clinical
      description and available standardised methods. The specific characteristics of
      psychiatric disorders in respect of social cognition, therefore, may vary
      according to the hierarchical organisation of the social module. Systematic
      studies on social reasoning processes in psychiatric disorders may provide new
      insights also useful for the development of coping strategies in cognitive
      behavioural therapy.

PMID- 11244381
TI  - Toronto Alexithymia Scale in outpatients with sexual disorders.
AB  - The Toronto Alexithymia Scale (TAS-26) was administered to patients with sexual
      disorders (n = 112) and to healthy control subjects (n = 94). The clinic sample
      was divided into three subgroups according to DSM-III-R criteria: patients with
      hypoactive sexual desire disorder (n = 41), patients with orgasm disorders (n =
      51) and patients with male erectile disorder (n = 20). TAS scores were
      significantly higher for male and female patients with hypoactive sexual desire
      disorder, and with male erectile disorder than controls. The TAS scores in the
      orgasm disorder patients were not significantly different from those of controls.
      These results are interesting because they show an association betweeen
      alexithymia and some sexual symptoms.

PMID- 11244382
TI  - Immediate and delayed memory performance in schizophrenia spectrum patients: use
      of matched tasks.
AB  - Rapid forgetting has been observed in long-term schizophrenic patients in the
      past. In this study, the rate of forgetting was assessed in short-term
      schizophrenic, schizophreniform and schizoaffective patients who had positive
      symptoms in the past, and in schizophreniform patients who never had positive
      symptoms. Four groups of patients representing these distinctions and a group of
      normal controls were assessed using immediate and delayed recall tasks, while
      controlling for effects of discriminating power of tasks, using matched-task
      methodology. The results showed that all schizophrenia spectrum patients with
      positive symptoms showed rapid forgetting as compared to schizophreniform
      patients with negative symptoms and normal controls. It is concluded that better
      immediate than delayed recall characterizes schizophrenia spectrum patients who
      have had positive symptoms. However, schizophrenia spectrum patients with
      negative symptoms may be qualitatively different from patients with positive
      symptoms in showing a slower rate of forgetting. The results support the
      hypothesis that there is at least one and possibly two brain dysfunctions
      affecting memory in schizophrenia.

PMID- 11244383
TI  - A case of paranoia with severe consequences. From a historical approach to a
      multidimensional understanding of chronic delusional disorder.
AB  - Following a brief resume of the history of the notion of paranoia, we present the
      case history of a 67-year-old female patient, who suffered from irreversible
      physical handicap as a result of chronic delusion. Against the background of the
      on-going controversy about the existence of paranoia as a distinct illness, we
      discuss the contemporary understanding of delusional disorders, emphasising the
      importance of a multidimensional therapeutic approach.

PMID- 11244384
TI  - Birth order and schizophrenia in Austria and Pakistan.

PMID- 11244386
TI  - "Body image" drugs: a growing psychosomatic problem.

PMID- 11244387
TI  - Perceived difficult temperament, hostile maternal child-rearing attitudes and
      insulin resistance syndrome precursors among children: a 3-year follow-up study.
AB  - BACKGROUND: We prospectively examined the relationship between latent constructs
      of perceived difficult temperament and hostile maternal child-rearing attitudes
      on the one hand, and the cluster of multiple cardiovascular risk factors
      comprising the insulin resistance syndrome (IRS) on the other. METHODS: A 3-year
      follow-up study of 451 randomly selected healthy children was used. The
      temperament of the children and maternal child-rearing attitudes were self-rated
      by the mothers. The physiological parameters measured were serum insulin, high
      density lipoprotein cholesterol (HDL-C), triglycerides, systolic blood pressure,
      body-mass index and subscapular skinfold thickness. We analyzed the data using
      structural equation models that involved specific paths allowing separation, and
      tests of both unique and common (latent) aspects of measured variables. RESULTS:
      Among boys we found a cross-lagged effect between the latent constructs of
      perceived difficult temperament and IRS, as well as 1 specific effect from
      hostile maternal child-rearing attitudes to HDL-C. Among girls there were 6
      specific effects from specific measures of perceived temperamental difficultness
      or hostile maternal child-rearing attitudes that influenced the IRS or its
      components. CONCLUSIONS: The findings suggest that temperament and maternal child
      rearing attitudes may contribute to the early development of the IRS in a gender
      specific way among children, thereby potentially increasing the risk of coronary
      heart disease later in life.

PMID- 11244388
TI  - Maternal expressed emotion and metabolic control of children and adolescents with
      diabetes mellitus.
AB  - BACKGROUND: The objectives of this study of children and adolescents with
      diabetes were to: (1) examine whether maternal expressed emotion (EE), in the
      form of critical comments (CC), hostility and emotional overinvolvement (EOI), is
      related to metabolic control; (2) determine if CC and EOI are separately related
      to poor metabolic control, and (3) ascertain whether high EE is related to
      psychopathology in these children. METHODS: The Present Episode version of the
      Schedule for Affective Disorders and Schizophrenia for School-Age Children
      (Kiddie-SADS-P/K-SADS-P) interview was administered to 55 children and
      adolescents with diabetes and the parental EE instrument, the 5-min speech
      sample, to 55 mothers. The same instruments were utilized with the 54 controls
      and their mothers. Glycosylated hemoglobin A1 values were used as a measure of
      metabolic control. RESULTS: More than half of the children with diabetes (58.2%)
      had mild to moderate symptoms of anxiety or depression as compared to 9.3% of the
      controls. High EE was exhibited by 70.9% of the index group mothers in contrast
      to only 29.6% of the control group mothers. High maternal EE was not related to
      the psychopathology of children with diabetes. High maternal EE and in particular
      its EOI component and excessive detail (a subcategory of EOI) were related to
      poor metabolic control of the index children. CONCLUSIONS: Maternal EE is related
      to metabolic control in childhood diabetes; maternal EOI in particular is related
      to poor metabolic control. Mental health professionals should work with mothers
      of children with diabetes in an effort to modify such attitudes and emotions.

PMID- 11244389
TI  - Preliminary evidence for Herpes labialis recurrence following experimentally
      induced disgust.
AB  - BACKGROUND: After primary orofacial infection with the herpes simplex virus (type
      1, HSV-1), up to 40% of HSV seropositive subjects suffer recurrent herpes
      infections which are characterized by painful erosions of the involved skin
      mainly around the lips (herpes labialis). Besides various other factors, there is
      growing evidence suggesting that psychosocial factors might trigger HSV. The
      present study was designed to investigate modulation of recurrent HSV infection
      by experimentally induced emotional distress. METHODS: Among patients with herpes
      labialis (n = 91), subjects who showed recurrent HSV infection (>5 acute
      infections/year) and who reported to suffer from HSV symptoms exclusively after
      confrontation with dirty dishes, i.e. dirty plates or dirty glasses were selected
      by standardized interview. Subjects (n = 20) were randomly assigned to two
      treatment groups. The experimental group (n = 10) was first exposed to 5 slides
      showing dirty glasses and subsequently to the glasses previously presented on the
      slides in vivo. The control group (n = 10) was exposed to neutral slides and
      neutral objects. In order to determine the proportion of leukocyte subpopulations
      and concentrations of tumor necrosis factor alpha (TNF-alpha), blood samples were
      collected 15 min before as well as 40 min and 48 h after stimulus presentation.
      Saliva cortisol was obtained 45, 20, 15 and 1 min before and 1, 10, 20 and 30 min
      after stimulus confrontation. RESULTS: Medical examination of the volunteers 48 h
      after the experiment indicated that four experimental subjects showed HSV-1
      symptoms while not a single herpetic infection could be determined in the control
      subjects (p = 0.033). Moreover, significantly elevated concentrations of TNF
      alpha were observed in the experimental, but not in the control group. No
      significant alterations of the number of leukocyte subpopulations were found 30
      min or 48 h after stimulus presentation. Further, cortisol concentrations were
      found to be unchanged after the treatment. CONCLUSIONS: The present findings
      suggest that experimentally induced emotional stress such as disgust may be
      associated with reactivation of HSV.

PMID- 11244390
TI  - Intact physiological response to arousal with impaired emotional recognition in
      alexithymia.
AB  - BACKGROUND: The purpose of the present study was to clarify the relationship
      between the recognition of emotion and physiological response to emotion (i.e.
      arousal) in alexithymia. METHODS: This study investigated differences in
      physiological arousal state, as measured by continuous heart rate, electrodermal
      activity (EDA) and self-reported emotional intensity before and after exposure to
      an emotionally arousing or neutral videotape among 41 high- or low-alexithymic
      young adult participants. RESULTS: Across subjects, emotionally negative stimuli
      produced increased physiological arousal. However, high-alexithymic participants
      exposed to the arousing videotape did not report increased subjective emotional
      intensity, as did low-alexithymic participants. In addition, the baseline EDA of
      high-alexithymic participants was significantly higher than that of the low
      alexithymic participants. CONCLUSIONS: Results support the prediction that
      alexithymia leads to a decoupling between subjective and physiological arousal
      when exposed to emotionally negative stimuli. This decoupling may increase
      alexithymic individuals' risks for stress-related illness.

PMID- 11244392
TI  - Short-term group therapy for patients with chronic fatigue syndrome.
AB  - BACKGROUND: This study presents experiences of focused short-term group therapy
      for patients with chronic fatigue syndrome (CFS). METHODS: Fourteen women
      diagnosed as CFS patients were randomly placed into two groups. The control group
      received group therapy 5 months after the first group. The project consisted of
      10 group sessions of 1.5 h per week. Sense of coherence (SOC) was used for
      measuring coping resources, and self-rating scales of quality of life and of
      fatigue were compared before and after group therapy. RESULTS: The most valuable
      aspect was the sharing of experiences. More than half of the patients also felt
      that the sessions had improved psychological well-being through adjustment of
      ambitions and improved coping with symptoms. CONCLUSION: The study encourages
      further research. If group therapy is chosen as treatment for these patients, a
      longer period is recommended. A possible alternative is individualized short-term
      therapy adapted to each patient's needs, problems and circumstances.

PMID- 11244393
TI  - Psychotherapy in postgraduate psychiatric training: attitudes of residents.

PMID- 11244391
TI  - Management of major depression in the primary care setting.
AB  - BACKGROUND: Patients treated in community clinics, particularly those of minority
      status, may rely more heavily on primary care physicians (PCPs) for the diagnosis
      and management of depression. We wished to determine how PCPs in a community
      clinic setting initially manage patients newly diagnosed with major depression.
      METHODS: 698 patients were screened for major depression by the Structural
      Clinical Interview for DSM-III-R in a community-based primary care health center.
      Forty outpatients (29 Hispanic) were found to suffer from major depression. A
      letter explaining positive findings was sent to the patients' PCPs. Medical
      record charts were reviewed 3 months later to determine the PCP's management
      following the diagnosis. RESULTS: Of the 38 patients who remained in the study at
      3 months, 20 (53%) received no intervention from the PCP by the end of 3 months
      after diagnosis, and of these, 14 were Hispanic. Five (13%) were prescribed an
      antidepressant by the PCP. Nine (24%) were referred to mental health services for
      medication, psychotherapy or combination treatment. Four (11%) were prescribed an
      antidepressant and then referred to mental health services. Differences between
      management of Hispanic and non-Hispanic patients were not statistically
      significant. CONCLUSIONS: Independent screening by psychiatrists in primary care
      settings may not be adequate enough to ensure appropriate management of
      depression by PCPs. Possible explanations may include time constraints during
      primary care visits, patient and/or physician reticence, and insufficient
      education of PCPs about depression.

PMID- 11244396
TI  - Planning for business independence.

PMID- 11244395
TI  - Standards of Practice for Case Management.

PMID- 11244397
TI  - e-Medx, Inc.'s e-POC for cancer.

PMID- 11244398
TI  - Therapies for cancer.

PMID- 11244399
TI  - HIPAA privacy and security regulations.

PMID- 11244400
TI  - Benchmark service for providers.

PMID- 11244401
TI  - Social health maintenance organizations, Part II.

PMID- 11244402
TI  - A guiding framework for delivering culturally competent services in case
      management.

PMID- 11244403
TI  - The impact of the rehabilitation prospective payment system on case management.

PMID- 11244404
TI  - Growth hormone therapy in adults: what case managers need to know.

PMID- 11244405
TI  - Case managers tread the muddied ethical waters of HIPAA.

PMID- 11244406
TI  - Functional therapy: The art of exaggeration?

PMID- 11244408
TI  - Jones jig and correction of a Class II malocclusion.

PMID- 11244409
TI  - From treatment planning to treatment results: The luck of the draw?

PMID- 11244410
TI  - Concertacesion.

PMID- 11244411
TI  - Early treatment and long-range forecasting.

PMID- 11244412
TI  - Where has all the arch length gone?

PMID- 11244413
TI  - Incorporating retained deciduous teeth in orthodontic therapy.
AB  - While patients with hypodontia of the permanent dentition constitute a relatively
      small portion of the general population, a significant percentage of these
      patients will require orthodontic therapy. This is a case report in which the
      family opted to maintain the retained deciduous teeth rather than seek combined
      orthodontic-prosthodontic treatment.

PMID- 11244415
TI  - Factors that relate to treatment duration for patients with palatally impacted
      maxillary canines.
AB  - The objectives of this study were to determine the relationship between the
      initial position of a palatally impacted maxillary canine (as seen on a panoramic
      radiograph) and the duration of orthodontic treatment and to determine whether a
      difference in treatment duration existed between patients with bilateral
      palatally impacted canines and patients with unilateral impaction. A total of 47
      adolescent subjects were chosen (9 subjects with unilateral impactions and 18
      subjects with bilateral impactions). All subjects had full fixed orthodontic
      appliances placed. The treatment duration of this group was compared with that of
      a control group with similar characteristics but without the impacted canine. The
      results showed that the average duration of treatment was 22.4 months for the
      control group, 25.8 months for the unilateral-impacted group, and 32.3 months for
      the bilateral-impacted canine group. The length of treatment for the impacted
      canine sample was related to the age of the patient at the start of treatment;
      younger patients required a longer treatment. The younger the patient, the more
      severely impacted the canine. The bilateral-impacted canine group had at least 1
      canine that was more severely impacted than the impacted canine in the unilateral
      impacted group. If the canine was impacted less than 14 mm from the occlusal
      plane, treatment duration averaged 23.8 months; if the canine was impacted more
      than 14 mm from the occlusal plane, treatment duration averaged 31.1 months.

PMID- 11244414
TI  - Comparison of dental arch measurements in the primary dentition between
      contemporary and historic samples.
AB  - The purpose of this study was to investigate secular changes that may have
      occurred in dental arch dimensions by comparing a sample of contemporary North
      American white children (born between 1992 and 1995) in the primary dentition to
      those children found in an earlier study of North American white children (born
      between 1946 and 1948). The sample of contemporary children has been followed
      prospectively since birth and was assessed at 4(1/2) to 5 years of age. Data for
      the historic sample were obtained from 5-year-old children who were enrolled in
      the Iowa Growth Study. The 2 samples were similar in terms of geographic
      location, racial and ethnic backgrounds, and socioeconomic status. To further
      enhance the comparison and to match the 2 groups, the 2 samples were restricted
      to white children with a normal overjet (<4 mm) and normal anteroposterior molar
      relationship, no anterior open bite, and no crossbite. In addition, individuals
      were excluded if any permanent teeth were erupted. Measurements of maxillary and
      mandibular arch lengths and intercanine and intermolar arch widths were made,
      with measurements of overjet and overbite. The results indicated that maxillary
      and mandibular arch lengths in both sexes were significantly shorter in the
      contemporary sample; all arch widths were significantly smaller in contemporary
      boys, but not in girls. These findings suggest that average arch dimensions may
      be smaller in contemporary children than in past generations. Further research is
      needed to determine whether smaller arch dimensions are associated with more
      crowding in the primary, mixed, and permanent dentitions.

PMID- 11244416
TI  - Eruption of third permanent molars after the extraction of second permanent
      molars. Part 1: Assessment of third molar position and size.
AB  - The eruptive path of third molars after extraction of second molars was examined
      in 63 patients. Panoramic radiographs from the start and the end of active
      treatment and 3 or more years after treatment were assessed. Study models were
      used to compare the size of the second and third molars and to assess the final
      position of the third molars. All third molars erupted; none became impacted.
      During eruption, maxillary third molar crowns uprighted and maintained their
      angulation as they came into occlusion. Mandibular third molar crowns continued
      to upright significantly mesiodistally after active treatment, with space closure
      the result of horizontal translation rather than mesial tipping. Further
      uprighting occurred once occlusion was established, although few became as
      upright as the second molars they replaced. However, mandibular third molar roots
      were frequently curved distally, thus the third molar crown position was
      invariably better than the overall tooth angulation would suggest, by 16.5
      degrees on average. Model analysis (Richardsons' scoring system) showed 96% of
      mandibular and 99% of maxillary third molars erupted into a good or acceptable
      position. Limitations of this scoring system are discussed. The mesiodistal size
      of third molars was suitable to replace second molars; on average, mandibular
      third molars were 0.55 mm larger and maxillary third molars were 0.7 mm smaller
      than second molars.

PMID- 11244417
TI  - Eruption of third permanent molars after the extraction of second permanent
      molars. Part 2: Functional occlusion and periodontal status.
AB  - Functional occlusion and periodontal health were investigated after orthodontic
      treatment that involved extraction of second molars and after eruption of the
      third molars in 37 patients (25 female, 12 male). The mean age was 21 years 9
      months (range, 16 years 1 month-30 years 5 months). The third permanent molars
      invariably erupted into a position that maintained good functional occlusion.
      Sixty-three percent of patients had canine guidance in lateral excursion; the
      remainder of patients had satisfactory group function. There were only 2 non
      working side interferences in the sample, 1 from a recently erupted mandibular
      third molar. The periodontal health of the sample was generally excellent. Plaque
      score and bleeding on probing was very low (1.7% of sites). Periodontal health
      around both maxillary and mandibular teeth was extremely good. When attachment
      loss was assessed, 2238 of 2240 sites were clinically healthy. One patient, who
      had generally poor oral hygiene, had a 4-mm probing depth interproximally on the
      maxillary first and third molar contact. There was no correlation between
      periodontal health and mandibular third molar position. Therefore, both
      functional occlusion and periodontal health in the sample were good after loss of
      second permanent molars and eruption of the third molars.

PMID- 11244418
TI  - Presence of third molar germs in orthodontic patients in Japan.
AB  - The purpose of this investigation was to evaluate the existence of third molar
      germs in orthodontic patients in Japan and to examine the relationship between
      the existence of third molars and sagittal maxillomandibular jaw relationships.
      The subjects comprised 306 patients from the orthodontic clinic of Hokkaido
      University Dental Hospital who were younger than 15 years. The subjects were
      divided into 2 groups: 1 group included 144 patients who were born between 1966
      and 1969 (60s group), and the other group included 162 patients who were born
      between 1980 and 1987 (80s group). Assessments were made from panoramic
      radiographs and lateral cephalograms. The following results were obtained: (1)
      all 4 third molar germs were present in 77% of subjects, (2) mandibular third
      molars were present significantly more often than maxillary third molars, and (3)
      the percentage of skeletal Class III subjects who had all 4 third molars was
      lower than that of skeletal Class II subjects. The chi(2) test was used to
      determine statistical significance in differences.

PMID- 11244419
TI  - Shear bond strength of stainless steel orthodontic brackets with a moisture
      insensitive primer.
AB  - The purposes of this study were (1) to evaluate the shear bond strength of
      stainless steel orthodontic brackets bonded to dry and wet (with water and
      saliva) etched enamel with the use of the moisture-insensitive primer (MIP;
      Transbond; 3M Unitek, Monrovia, Calif) and (2) to evaluate the effectiveness of
      MIP with chemically activated (Concise; 3M Dental Products, St Paul, Minn) and
      light-activated (Transbond XT; 3M Unitek) resin. One hundred forty-four freshly
      extracted bovine teeth were divided into 12 groups (n = 12 teeth), and brackets
      were bonded with either of the 2 resins in combination with the conventional
      primer or MIP in dry or wet enamel surface conditions. The test specimens were
      mounted in a screw-driven mechanical testing machine (model 4204; Instron Corp,
      Canton, Mass) and subjected to a crosshead speed of 0.5 mm/min. The data were
      analyzed by 2-way analysis of variance. MIP with Concise produced slightly higher
      bond strengths compared with the conventional primers under wet conditions (MIP
      vs conventional: saliva, P <.001; water, P =.004). However, MIP in combination
      with Transbond XT produced comparable bond strengths on both the dry and wet
      etched enamel (dry, 10.14 MPa; water, 9.69 MPa; saliva, 8.90 MPa). The results of
      this study suggest that MIP be used only with light-activated composite resins.

PMID- 11244420
TI  - Comparative assessment of light-cured resin-modified glass ionomer and composite
      resin adhesives: in vitro study of a new adhesive system.
AB  - The ideal adhesive system is one that prevents decalcifications and has
      sufficient bond strength to withstand untimely impact forces on bonded brackets.
      The purpose of this investigation was to study and compare the bond strengths and
      adhesive remnant indexes of light-cured resin-modified glass ionomer and
      conventional resin adhesives. A new light-cured resin-modified glass ionomer
      adhesive was compared with the conventional adhesive systems. The effects of the
      new adhesive, with a system of etching and using adhesive promoters on the tooth
      enamel, as well as microetching the brackets, were analyzed. Comparisons were
      made (analysis of variance and the Tukey method) between this and other adhesive
      systems. The new adhesive system is indicated where prevention of decalcification
      and increased bond strength in noncompliant patients are indicated.

PMID- 11244421
TI  - The effect of short-term temperature changes on superelastic nickel-titanium
      archwires activated in orthodontic bending.
AB  - The bending stiffness of superelastic nickel-titanium archwires is influenced by
      alterations in mouth temperature. The activation and deactivation phases of a
      load-deflection loop of superelastic wires have different stress-magnitudes. This
      investigation compared the effect of short-term cooling or heating on the bending
      force exerted by nickel-titanium archwires. Two rectangular superelastic and one
      conventional nickel titanium wire were tested in bending at 37 degrees C. The
      specimens were tested during the activation phase and during the deactivation
      phase. The wires were kept at constant strain and the bending force was measured
      continually while the activated specimens were subjected to cold (10 degrees C)
      or hot (80 degrees C) water. The test situation simulates a patient's archwire
      that is subjected to cold or hot drinks or food during a meal. The conventional
      nickel-titanium wire was marginally affected by brief cooling or heating,
      regardless of activation phase. In contrast, the superelastic wires were strongly
      affected by short-term application of cold or hot water. When tested in
      activation phase, the effect of heating was transient whereas the wires continued
      to exert sub-baseline bending forces after short-term application of cold water.
      When tested in deactivation phase, the effect of cooling was transient whereas
      the wires exerted supra-baseline bending forces after a short-term application of
      hot water. The effect of short-term temperature changes on the bending stiffness
      of superelastic nickel titanium archwires is dependent upon the bending phase.
      Cooling induced transient effects on a wire in its deactivation phase, but
      prolonged effects when the wire was tested in the activation phase. In contrast,
      the effect of short-term heating was transient when the wire was tested in the
      activation phase, but prolonged when the wire was tested in the deactivation
      phase.

PMID- 11244422
TI  - Mechanical characteristics of various tempers of as-received cobalt-chromium
      archwires.
AB  - The mechanical characteristics of 24 of the 36 wire cross-sectional
      configurations were investigated in the as-received state from among the 4
      tempers of a cobalt-chromium product. After engineering mechanics were used to
      validate the efficacy of the span combinations, each wire was measured in flexure
      to determine its elastic modulus and in tension to determine its yield strength,
      ultimate tensile strength, and ductility. Other combined characteristics were
      evaluated, including flexibility, resilience, and the yield strength criterion.
      In these as-received materials the formability sometimes followed expectations,
      but the flexibility and resilience characteristics were variable and independent
      of temper. And although the elastic modulus was independent of testing
      parameters, it was affected by the loss of material at the corners of rectangular
      wires. Overall, the stiffnesses of cobalt-chromium wires in round configurations
      were comparable to those of multi- and single-stranded stainless steel wires but
      were 3 and 6 times greater than the stiffnesses of beta-titanium and nickel
      titanium wires, respectively. In the final analysis, these as-received wires do
      not meet their potential as a variably formable and variably resilient
      alternative to stainless steel. Perhaps this is why cobalt-chromium wires have
      never had the impact on the profession that was expected from them several years
      ago.

PMID- 11244423
TI  - A comparison between friction and frictionless mechanics with a new typodont
      simulation system.
AB  - This study was designed to explore the differences between friction and
      frictionless mechanics for maxillary canine retraction with the use of a new
      typodont simulation system, the Calorific machine system. The unit was designed
      to observe the whole process of tooth movement and is composed of 3 parts: a
      temperature regulating system, electrothermodynamic teeth, and an artificial
      alveolar bone component. The efficiency of maxillary canine retraction was
      compared with the sliding mechanics (along a.016 x.022-in stainless steel labial
      arch and nickel-titanium closed coil spring) and a canine retraction spring. The
      patterns of tooth movement obtained with both of these mechanics were measured 5
      times each. Friction mechanics were superior to frictionless mechanics in terms
      of rotational control and dimensional maintenance of the arch (P <.0001);
      frictionless mechanics were shown to be more effective at reducing tipping and
      extrusion (P <.0001). However, the observed differences between the 2 methods
      were relatively small in terms of their clinical significance, and no differences
      were found in anchorage control (P =.2078). In conclusion, this study indicated
      that friction and frictionless mechanics perform similarly.

PMID- 11244424
TI  - Intraoral aging of the inner headgear component: a potential biocompatibility
      concern?
AB  - The effect of intraoral aging of biomaterials on the modification of their
      surface properties has mostly been unknown. The purpose of this study was to
      investigate and characterize surface alterations of retrieved inner face-bow
      headgear components. Specimens were prepared from 3 areas of retrieved headgear
      wires: inner-outer face-bow soldered junction, buccal segment, and projection
      entering the buccal tube. Specimens from as-received headgear wires that matched
      the brand and size of the retrieved wires were also fabricated; all specimens
      were then subjected to multitechnique characterization. Optical microscopy
      revealed extensive biofilm islands of amorphous precipitants and accumulated
      microcrystalline particles. Micro-multiple internal reflectance Fourier transform
      infrared spectroscopy investigation of the retrieved wire samples demonstrated
      the presence of a proteinaceous biofilm, the organic constituents of which were
      mainly amide, alcohol, and carbonate. Scanning electron microscopy and
      radiographic microanalysis showed that the elemental species precipitated on the
      material surface were mainly calcium and phosphorus, forming calcium-phosphorus
      precipitates with thicknesses reaching 300 microm, whereas radiograph
      fluorescence spectrometry provided evidence of integument calcification through
      identification of calcium and phosphorus peaks. The clinical implication of the
      aging pattern that was identified relates to the potential protective role or
      induction of disintegration by the biofilm adsorbed on the wire that affected the
      biocompatibility of the alloy. Whereas further investigation is suggested for the
      clarification of the effect of intraoral aging on ionic release, the results of
      this study emphasize the necessity for the incorporation of in vivo approaches,
      including retrieval analyses, in the study of the biologic performance of
      orthodontic materials.

PMID- 11244425
TI  - Orthodontic tooth movement and de novo synthesis of proinflammatory cytokines.
AB  - Interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor
      alpha (TNF-alpha) are proinflammatory cytokines that are thought to play a role
      in bone remodeling, bone resorption, and new bone deposition. In the present
      work, in situ hybridization was performed to measure the messenger RNA expression
      of IL-1beta, IL-6, and TNF-alpha at 3, 7, and 10 days after the application of
      orthodontic force on the maxillary first molars of 12 rats. The contralateral
      side and 3 untreated rats served as controls. Measurements of the messenger RNA
      expression were selected as the means to investigate the role of orthodontic
      force in de novo synthesis of proinflammatory cytokines. After the application of
      force, the induction of IL-1beta and IL-6 was observed to reach a maximum on day
      3 and to decline thereafter. No messenger RNA induction of either cytokine was
      measured in the control teeth. The messenger RNA expression of TNF-alpha was not
      detected at any time point of this study in the experimental or contralateral
      sides or in the control animals. Our data support the hypothesis that these
      proinflammatory cytokines may play important roles in bone resorption after the
      application of orthodontic force.

PMID- 11244426
TI  - Prevalence of malocclusion among Latino adolescents.
AB  - Although numerous studies have documented malocclusion in various ethnic groups
      in the United States, the prevalence of malocclusion in the Latino population is
      not well known. The Latino population may be the largest minority group in the
      United States by the year 2004. This study analyzes the occlusion of 507 Latino
      adolescents between the ages of 12 and 18 years. More than 93% of the subjects
      demonstrated some form of malocclusion. The distribution of malocclusion patterns
      is presented and contrasted with data published for other ethnic groups.
      Information about the prevalence and types of malocclusion in the Latino
      population should be of interest to general dental practitioners and specialists.

PMID- 11244427
TI  - Changes in the TMJ disc-condyle-fossa relationship following functional treatment
      of skeletal Class II Division 1 malocclusion: a magnetic resonance imaging study.
AB  - A detailed clinical examination of the parts of the temporomandibular joint can
      be carried out by means of magnetic resonance imaging. The aim of this study was
      to examine, with the use of magnetic resonance imaging, the mandibular condyle
      disc-fossa relationship in subjects with Class II Division 1 malocclusions who
      were treated with the Andresen activator. The sample consisted of 18 subjects
      with Class II Division 1 malocclusion, 9 treated with the Andresen activator and
      9 control subjects. Unilateral magnetic resonance images, lateral cephalograms,
      and hand-wrist films were taken for each subject at the beginning and end of the
      treatment or observation period. The anterior, posterior, and superior joint
      spaces were measured on the magnetic resonance images, and the posterior, medial,
      and anterior disc angles were measured for the determination of the disc
      position. The changes that occurred during the treatment and observation periods
      were examined by means of a paired t test and an analysis of variance. The
      condyle was found to be located anteriorly. However, the changes in the disc
      position were found to be statistically insignificant.

PMID- 11244428
TI  - A bonded functional ramp to aid in asymmetric expansion of unilateral posterior
      crossbites.
AB  - Unilateral posterior crossbite is a common finding in patients seeking
      orthodontic treatment. When treating this condition with a rapid maxillary
      expander, clinicians occasionally observe no resolution of the crossbite and
      document an unnecessary overexpansion of the contralateral dentition. This
      article describes a method for treating unilateral posterior crossbite and,
      specifically, the lack of crossbite correction after expansion with a rapid
      maxillary expander. A composite ramp is bonded to the mesial buccal cusp of the
      maxillary first molar in crossbite. The necessary materials and instruments are
      typically found in an orthodontic office. This adjunctive procedure requires no
      more than 5 extra minutes during an examination, and no additional appointments
      are necessary.

PMID- 11244429
TI  - Orthodontic technolocity.

PMID- 11244430
TI  - An affair to remember.

PMID- 11244431
TI  - Umbilical cord blood for allogeneic transplantation in children and adults.
AB  - Early clinical reports outlining outcomes for primarily pediatric patients
      undergoing UCB transplantation, point to delayed time to hematopoietic recovery,
      and favorable incidence and severity of graft-versus-host disease. Intensive
      clinical and laboratory research is ongoing focused on strategies to foster UCB
      allogeneic donor engraftment, thereby allowing wider application of this stem
      cell source for patients requiring allogeneic transplantation.

PMID- 11244432
TI  - Bigger is better: maternal and neonatal predictors of hematopoietic potential of
      umbilical cord blood units.
AB  - Umbilical cord blood (CB) is a useful stem cell source for patients without
      matched family donors. CB banking is expensive, however, because only a small
      percentage of the cord units stored are used for transplantation. In this study,
      we determined whether maternal factors, such as race, age, and smoking status
      have an effect on laboratory parameters of hematopoietic potential, such as
      viability, cell counts, CD34+ cell counts, and CFU-GM. We studied the effect of
      neonatal characteristics such as birth order, birth weight, gestational age, and
      sex of the baby on the same laboratory parameters. Race and maternal age had no
      effect on these laboratory parameters. In multivariate analysis, babies of longer
      gestational age had higher cell counts, but lower CD34+ cell counts and CFU-GM.
      Bigger babies had higher cell counts, more CD34+ cells, and more CFU-GM. Women
      with fewer previous live births also produced cord units with higher cell counts,
      CFU-GM, and CD34+ cell counts. Specifically, each 500 g increase in birth weight
      contributed to a 28% increase in CD34+ cell counts, each week of gestation
      contributed to a 9% decrease in CD34+cell counts, and each previous birth
      contributed to a 17% decrease in CD34+ cell counts (all P < 0.05). These data may
      be used to select the optimal cord blood donors and allow CB banks efficient
      resource allocation.

PMID- 11244433
TI  - Improved outcome of adult T cell leukemia/lymphoma with allogeneic hematopoietic
      stem cell transplantation.
AB  - Adult T cell leukemia/lymphoma (ATL) is a poor prognosis T cell malignancy. In
      order to improve the outcome, we employed allogeneic stem cell transplantation
      (allo-SCT) for ATL in 10 patients, nine of whom were from HLA-identical siblings
      and one from an unrelated donor. Conditioning regimens varied among the patients
      except that all received total body irradiation. The patients tolerated the
      regimens well with mild, if any toxicity, and engraftment occurred in all cases.
      Median leukemia-free survival after allo-SCT was 17.5+ months (range 3.7-34.4+).
      Six of the 10 patients developed acute GVHD (one case each with grade I, III or
      IV, and three cases with grade II) and three patients developed extensive chronic
      GVHD. Four patients died after allo-SCT during the study period from either acute
      GVHD (grade IV), pneumonitis, gastrointestinal bleeding or renal insufficiency.
      Two of the 10 cases with no symptoms of GVHD relapsed with clinical ATL. These
      results strongly suggest that allo-SCT may improve the survival in ATL if a
      controlled degree of GVHD develops.

PMID- 11244434
TI  - Transplant-related mortality in patients older than 60 years undergoing
      autologous hematopoietic stem cell transplantation.
AB  - Although high-dose therapy with autologous hematopoietic stem cell
      transplantation (ASCT) is a widely used method of dose intensification in
      patients with hematological malignancies, patients aged over 60 are generally
      excluded. We evaluated high-dose therapy and ASCT in 29 cases involving 27 such
      patients (median age 63 years; range 61-68) with different malignancies. Patients
      were eligible if they had a good performance status, normal cardiac, respiratory,
      and hepatic function and a serum creatinine concentration of less than 2 mg/dl
      (<5 mg/dl in myeloma patients). Engraftment was assessable in 27 procedures. The
      median time to attain 0.5 and 1 x 10(9) PMN/l was 13 days (range 9-30) and 14
      days (range 10-66), respectively. The median time taken to reach a platelet count
      greater than 50 x 10(9)/l was 14 days (range 8-223). Five patients (17%) died in
      the first 100 days after transplant, in two cases due to disease progression. The
      remaining three patients died as a consequence of transplant-related
      complications, with an overall transplant-related mortality of 10%. Five patients
      relapsed and died between 5 and 36 months after transplant. The remaining 17
      patients are still alive without disease progression, with an actuarial overall
      survival of 47% at 42 months (95% CI 33-61). We consider that high-dose therapy
      with ASCT should be considered in those elderly patients with good performance
      status and without general organ impairment.

PMID- 11244435
TI  - Feasibility and safety of peripheral blood stem cell transplantation from
      unrelated donors: results of a single-center study.
AB  - We compared the outcomes in patients receiving unrelated peripheral blood stem
      cell transplants (PBSCT) with those receiving bone marrow transplants (BMT) in a
      matched pair analysis. Seventy-four patients with hematological malignancies with
      HLA-matched (77%) and mismatched (23%) donors were analyzed in this study. Thirty
      four patients (45%) were considered as high risk patients. Sixty-eight patients
      received standard conditioning regimens with Bu/Cy or TBI/Cy. Six patients
      received an intensified conditioning regimen with the addition of etoposide,
      thiotepa or melphalan. GVHD prophylaxis consisted of prednisolone, cyclosporine
      and methotrexate. Groups were matched for patient, donor, transplant
      characteristics and HLA compatibility. Peripheral blood stem cell collection led
      to the collection of a higher number of CD34+ and CD3+ cells in comparison to
      bone marrow collection. Leukocyte engraftment in the PBSCT group occurred in 14
      days (median; range 6-26 days) and in the BMT group in 19 days (range 9-29 days;
      P < 0.02). The time of platelet engraftment did not differ significantly. The
      incidence of grades II-lV acute GVHD in the group of HLA-identical patients was
      35% in the PBSCT group and 25% in the BMT group (P < 0.33, log-rank). However,
      there was a significant difference (P < 0.05, log-rank) in incidence and time to
      onset of acute GVHD II-IV comparing all patients, including the 17 mismatched
      transplants. Disease-free survival was 51% (19 patients) with a median of 352
      days and 59% (21 patients) with a median of 760 days for PBSC and BMT
      transplants, respectively. In conclusion, our results indicate that allogeneic
      PBSCT led to significantly faster leukocyte engraftment but is associated with a
      higher incidence and more rapid onset of severe acute GVHD comparing all
      patients, including the 17 mismatched transplants. However, the incidence of
      severe acute GVHD in HLA-identical patients was not different between the PBSCT
      and BMT groups.

PMID- 11244436
TI  - High resolution HLA class I and II typing and CTLp frequency in unrelated donor
      transplantation: a single-institution retrospective study of 69 BMTs.
AB  - The results of unrelated donor transplantation (URD-BMT) are difficult to analyze
      since the continuous advances in HLA typing technology allow the detection of new
      mismatches unknown at the time of transplantation. We sought to confirm that
      matched recipient-donor pairs are in fact often mismatched when advanced HLA
      typing techniques are used. We retrospectively studied the impact of the results
      of high resolution HLA typing for HLA class I (-A, -B, -C) and HLA class II (-DR,
      -DQ, -DP) loci, and cytotoxic T lymphocyte precursor (CTLp) frequency, on the
      outcome of 69 URD-BMT procedures. At the time of transplant, six (6/69) and two
      (2/69) donor-recipient pairs were mismatched for HLA class I (-A and -B by
      serology) and HLA class II, respectively, while one pair was mismatched for both
      HLA class I and II. Using high resolution DNA typing, HLA class I mismatches were
      found in 31 (45%) pairs and HLA class II mismatches in nine (13%) pairs. Twenty
      three of the 69 pairs were HLA-C mismatched. Low CTLp frequencies were found
      among the 19 HLA class I matched pairs tested, and also in 5/14 mismatched pairs
      (of whom three had severe aGVHD). The overall survival of the cohort was 28 +/-
      6%. Among the 33 patients who were fully matched with their donors, the survival
      rate was 66% in the 18 patients with a standard hematological risk and 9% in the
      15 high risk patients. Only two of the 33 patients developed severe aGVHD, and
      only one had graft rejection. Among the 36 mismatched pairs, the survival rate
      was 31% in the 13 patients with a standard hematological risk and 8% in the 23
      high risk patients. Sixteen of these 36 patients died from severe aGVHD and four
      had graft failure or rejection. Three of the 10 patients with only an HLA-C
      mismatch died from severe aGVHD, and two had graft rejection. IN CONCLUSION: (1)
      donor-recipient matching based on high resolution HLA class I and II DNA typing
      is associated with significantly better outcome after URD-BMT; (2) the results of
      URD-BMT with classical GVHD prevention are comparable to those of geno-identical
      BMT when donor and recipient are fully matched for HLA-A, -B, -C, -DRB1 and -DQB1
      on the basis of high resolution typing; (3) CTLp frequencies do not correlate
      constantly with HLA class I matching, and our results fail to show that CTLp
      assay can distinguish between permissible and non-permissible class I mismatches;
      (4) clinical trials involving donor-recipient pairs with known HLA class I
      mismatches are needed to improve aGVHD prevention without increasing graft
      failure rate.

PMID- 11244437
TI  - A three or more drug combination as effective therapy for moderate or severe
      chronic graft-versus-host disease.
AB  - We analyzed the results of a three or more drug combination as treatment for
      moderate or severe cGVHD developing after transplantation for thalassemia, in 45
      patients with median age of 11 (range 2-26) years. Eighteen patients received a
      three drug regimen with cyclosporine (CsA), methylprednisolone (MP) and
      azathioprine (AZ) as first line therapy, 16 patients received this regimen as
      salvage therapy and 11 patients were given a four or five drug regimen with CsA,
      MP, AZ, cyclophosphamide (CY) and/or methotrexate (MTX) mainly as salvage
      therapy. The overall complete response (CR) rate was 77.3%, with 94% of CR in
      patients receiving the three drug regimen as first line, 88% in patients
      receiving it as salvage therapy and 36.6% in patients given the four or five drug
      regimen. The probability of CR in patients given the three drug regimen as first
      or salvage therapy or the four/five drug regimen was 89%, 53% and 30%, while the
      probability of survival was 89%, 65% and 58%, respectively. The incidence of
      treatment failure was low in our patients. Patients treated with the three drug
      regimen as first line therapy had less treatment-related complications than
      patients receiving this regimen as salvage therapy or patients given the four or
      five drug regimen. The main causes of treatment-related mortality (20%) were
      infectious complications. This retrospective study showed that a three or more
      drug combination is safe and effective for treatment of moderate or severe cGVHD
      at least in younger patients.

PMID- 11244438
TI  - Ex vivo generation of cytotoxic T lymphocytes specific for one or two distinct
      viruses for the prophylaxis of patients receiving an allogeneic bone marrow
      transplant.
AB  - Human adenovirus (AdV) infection and EBV-lymphoproliferative disease (LPD) are
      serious complications following allogeneic stem cell transplantation. In the
      healthy individual these viruses cause minor, self-limiting diseases but in the
      immunocompromised patient they are responsible for significant morbidity and
      mortality. The limitations of anti-viral drugs and a better understanding of the
      cellular immune response to viral pathogens have prompted interest in developing
      adoptive immunotherapy for transplant patients. Ex vivo expanded cytotoxic T
      lymphocytes (CTLs) specific for EBV have been used effectively both as
      prophylaxis against EBV-LPD and as treatment of established EBV+ lymphoma. To
      generate CTLs specific for AdV, we infected immature dendritic cells with virus,
      in the presence of lipid, and subsequently used these cells to stimulate PBMNCs.
      Cytotoxicity assays showed that the resulting CTLs specifically lysed AdV
      expressing targets and that this was mediated predominantly by CD4+ T cells. To
      generate CTLs specific for both AdV and EBV, we developed a CD40 ligand co
      culture system to infect B-lymphoblastoid cell lines (LCLs) with high efficiency.
      PBMNCs from healthy AdV-seropositive donors were stimulated weekly with
      autologous AdV+-LCLs. Chromium release assays demonstrated that the resultant
      CTLs had specificity against both EBV and AdV and that this was mediated by both
      CD4+ and CD8+ T cells. Our findings have potential implications for post
      transplant AdV and EBV immunotherapy in recipients of allogeneic stem cell
      transplants.

PMID- 11244439
TI  - Acute bleeding and thrombocytopenia after bone marrow transplantation.
AB  - The relationship between hemorrhage and low platelet count was first established
      in patients with acute leukemia, and has been widely applied to thrombocytopenic
      patients, including BMT patients. Yet, the role of thrombocytopenia in bleeding
      post BMT has not been systematically studied. We evaluated the risk of bleeding
      and outcome associated with thrombocytopenia in BMT patients who had prophylactic
      platelet transfusions at a trigger of 20 x 10(9)/l. Thrombocytopenia was
      investigated in 321 patients with moderate or severe bleeding (BLD), and in a
      matched comparison group of 287 patients who did not bleed (NBLD). Profound
      thrombocytopenia (< or = 10 x 10(9)/l) was found in 8.6% of the BLD patients
      during the week before the bleeding onset, significantly more frequent than in
      NBLD patients (2.1% to 4%, P < 0.02), during weeks 2 to 6 post BMT (the period
      when 75% of the bleeding initiated). On the first day of bleeding, platelet
      counts < or = 10 x 10(9)/l were found in 13.5%, 11-20 x 10(9)/l in 20.4%, and >
      20 x 10(9)/l in 66.1% of all episodes. Overall survival in BLD patients was not
      associated with the severity of thrombocytopenia before bleeding onset. Severity
      of thrombocytopenia was significantly associated with reduced survival in NBLD
      patients. We concluded that bleeding post BMT was significantly associated with
      thrombocytopenia, but the attributable risk of bleeding from profound
      thrombocytopenia was not large. Thrombocytopenia may be an important clinical
      sign in NBLD patients, and should be further explored in relation to acute
      toxicities other than bleeding.

PMID- 11244440
TI  - Prophylactic donor lymphocyte infusions after moderately ablative chemotherapy
      and stem cell transplantation for hematological malignancies: high remission rate
      among poor prognosis patients at the expense of graft-versus-host disease.
AB  - We investigated the use of 'prophylactic' donor lymphocyte infusions (DLI)
      containing 1 x 107 CD3+ cells, given at 30, 60 and 90 days post-allogeneic blood
      and marrow transplantation (BMT), following conditioning with fludarabine 30
      mg/m(2)/4 days and melphalan 70 mg/m(2)/2 days. GVHD prophylaxis consisted of
      cyclosporin A (CsA) 2 mg/kg daily with early tapering by day 60. Our goals were
      the rapid achievement of chimerism and disease control, providing an
      immunological platform for DLIs to treat refractory patients with hematological
      malignancies. Twelve heavily pre-treated patients with life expectancy less than
      6 months were studied; none were in remission. Diagnoses were AML (n = 4), MDS (n
      = 1), ALL (n = 3), CML (n = 3) and multiple myeloma (n = 1). Response rate was
      75%. Three patients are alive at a median of 450 days (range, 450-540). Two
      patients are in remission of CML in blast crisis and AML for more than 14 months.
      Median survival is 116 days (range, 25-648). Six patients received 12 DLIs; three
      patients developed acute GVHD after the first infusion and were excluded from
      further DLIs, but no GVHD occurred among patients receiving subsequent DLIs. One
      patient with CML in blast crisis went into CR after the first DLI. The overall
      incidence of acute GVHD was 70%. Primary causes of death were infections (n = 3),
      acute GVHD (n = 3), chronic GVHD (n = 1) and disease relapse (n = 2). We observed
      high response and chimerism rates at the expense of an excessive incidence of
      GVHD. DLI given at day +30 post BMT caused GVHD in 50% of the patients, and its
      role in this setting remains unclear.

PMID- 11244442
TI  - Atypical chronic graft-versus-host disease following interferon therapy for
      chronic myeloid leukaemia relapsing after allogeneic BMT.
AB  - We report a 54-year-old woman who received interferon alpha for haematological
      relapse of Ph-positive CML, 7 years after allogeneic BMT from an HLA-identical
      brother. Eighteen months after relapse, cytogenetic and molecular remission was
      achieved. She received interferon therapy for 25 months and it was discontinued
      when she developed skin lesions on her face and trunk, dysphagia and fever with
      respiratory failure and bilateral patchy airspace consolidation of the lung
      without microbiologic findings. Histologic features showed discoid lupus
      erythematosis, oesophagitis with pseudomembranes and a mixed pattern of
      lymphocytic bronchiolitis involving the alveoli and interstitial spaces all
      compatible with chronic GVHD. The patient was commenced on immunosuppressive
      therapy with complete clinical and radiological resolution. The available
      evidence supports an atypical presentation of chronic GVHD and suggests a role
      for interferon alpha in the pathogenesis of GVHD. To the best of our knowledge,
      this is the first case reported of severe chronic GVHD occurring during the
      course of interferon therapy for relapsed CML.

PMID- 11244441
TI  - Tetravalent meningococcal polysaccharide vaccine is immunogenic in adult
      allogeneic BMT recipients.
AB  - Forty-four adult BMT recipients transplanted from an HLA-identical sibling donor
      were randomized to receive meningococcal polysaccharide (Men PS) vaccine either 8
      (early group; 22 patients) or 20 (late group; 22 patients) months after BMT. The
      geometric mean concentrations (GMC) of antibodies to serogroup A Neisseria
      meningitidis (Men A) and serogroup C Neisseria meningitidis (Men C), determined
      by an EIA method, decreased during the first 6 months after BMT but remained at a
      stable level thereafter. Before vaccination the GMCs of anti-Men A were 1.53
      microg/ml and 1.61 microg/ml, but 1 month after vaccination they were
      significantly higher, 3.46 microg/ml and 6.39 microg/ml, in the early and late
      groups. The GMCs of anti-Men C increased from 0.37 microg/ml and 0.44 microg/ml
      before vaccination to 3.31 microg/ml and 4.62 microg/ml at 1 month after
      vaccination in the early and late groups, respectively. By 6 months after
      vaccination the GMCs of Men antibodies had decreased to levels of about 50% of
      those measured at 1 month after vaccination. Two-fold responses to Men A PS were
      seen in 52% and 74% and to Men C PS in 76% and 89% of the BMT recipients in the
      early and late groups, respectively. Chronic GVHD had no influence on the
      vaccination response. In the present study, Men PS vaccine induced good and equal
      antibody responses to Men A and Men C PSs in allogeneic BMT recipients regardless
      of timing after BMT. Vaccination against Neisseria meningitidis should be
      considered, especially in the event of travelling or military service > or = 8
      months after BMT.

PMID- 11244443
TI  - Successful autologous peripheral blood stem cell transplantation for relapsed
      intravascular lymphomatosis.
AB  - We describe a case of relapsed intravascular lymphomatosis (IVL) successfully
      treated with autologous PBSCT. A 59-year-old Japanese female patient with IVL who
      had achieved CR after six courses of biweekly CHOP therapy developed lymphoma.
      She achieved a second CR after six courses of modified biweekly CHOP therapy,
      followed by autologous PBSCH and high-dose chemotherapy (CBDCA, VP-16, MCNU, CY)
      with PBSCT. There has not been any evidence of recurrence 48 months after PBSCT.
      Our case suggests that PBSC is acceptable as a source for stem cell rescue in
      IVL.

PMID- 11244444
TI  - Epstein-Barr virus-related lymphoproliferative disease complicating childhood
      acute lymphoblastic leukemia: no recurrence after unrelated donor bone marrow
      transplantation.
AB  - A 16-year-old boy in complete remission of ALL, undergoing oral maintenance
      therapy, developed intestinal perforation related to EBV-associated
      lymphoproliferative disease (LPD). He was successfully managed with surgical
      resection, acyclovir, immunoglobulins and discontinuation of maintenance therapy.
      Leukemic marrow relapse occurred 3 months later, treated by polychemotherapy
      followed by unmanipulated BMT from a matched unrelated EBV seropositive donor.
      Donor lymphocytes were infused twice after transplant because of delayed
      immunologic recovery and severe CMV colitis. This was followed by acute GVHD
      requiring prolonged immunosuppressive treatment. Despite intensive and prolonged
      immunosuppression, recurrence of LPD was not observed. Following EBV-related LPD,
      allogeneic BMT can be performed if indicated. Selection of an EBV seropositive
      donor is of major importance for the prevention of LPD recurrence as the
      recipient may be protected by passive transfer of EBV-specific cytotoxic T cells.

PMID- 11244445
TI  - Successful unrelated bone marrow transplantation for Shwachman-Diamond syndrome.
AB  - A 5-year-old boy with Shwachman-Diamond syndrome underwent unrelated HLA
      identical bone marrow transplantation for severe pancytopenia. Conditioning was
      with busulfan, thiotepa and cyclophosphamide plus rabbit anti-lymphocyte serum.
      Engraftment for neutrophils and platelets was observed on days +18 and +41,
      respectively. Transplant-related side-effects were mild and transient. After a
      follow-up of 32 months, the patient is alive and enjoys a normal life, off any
      immunosuppressives. Immunological and hematological reconstitution is complete
      while other phenotypic characteristics (pancreatic insufficiency, short stature,
      femur dysostosis) are stable. Although experience in this field is scarce, we
      speculate that bone marrow failure in Shwachman-Diamond syndrome (even if not
      linked to the appearance of clonal disorders or leukemic transformation) is an
      indication for bone marrow transplantation and may be associated with a better
      outcome.

PMID- 11244446
TI  - Treatment of congenital erythropoietic porphyria in children by allogeneic stem
      cell transplantation: a case report and review of the literature.
AB  - Congenital erythropoietic porphyria (CEP) is a rare autosomal recessive disorder
      of porphyrin metabolism in which the genetic defect is the deficiency of
      uroporphyrinogen III cosynthase (UIIIC). Deficiency of this enzyme results in an
      accumulation of high amounts of uroporphyrin I in all tissues leading to
      hemolytic anemia, splenomegaly, erythrodontia, bone fragility, exquisite
      photosensitivity and mutilating skin lesions. We describe the case of a 23-month
      old boy who was cured of his CEP by a matched-sibling allogeneic bone marrow
      transplant, and review the published clinical experience regarding
      transplantation in this disease. He is alive and disease-free 15 months post
      transplant. All of his disease manifestations except for the erythrodontia have
      resolved. His UIIIC level and stool and erythrocyte porphyrin metabolites have
      almost completely corrected. He is the sixth child reported to be cured of this
      disease by stem cell transplantation, five cases being long-term survivors. If
      patients with this disease have an HLA-matched sibling, then stem cell
      transplantation should be strongly considered because this is currently the only
      known curative therapy.

PMID- 11244447
TI  - Acute heart failure after allogeneic blood stem cell transplantation due to
      massive myocardial infiltration by cytotoxic T cells of donor origin.
AB  - A 17-year-old male with AML FAB M4 relapsed 4 months after myeloablative
      conditioning and peripheral blood stem cell transplantation (PBSCT) from an HLA
      identical unrelated donor. A second PBSC harvest was infused 2 days after
      completion of cytoreductive therapy with mitoxantrone 7 mg/m(2)/day i.v. for 3
      days (total dose 21 mg/m(2)), fludarabine 30 mg/m(2)/day i.v. for 6 days (total
      dose 180 mg/m(2)) and Ara-C 125 mg/m(2)/day i.v. for 5 days (total dose 625
      mg/m(2)). Neutrophil recovery occurred on day +10 and was associated with GVHD
      grade III of the skin which was treated with cyclosporin A (CsA) and prednisone.
      Because of fever of unknown origin and progressive fatigue combined with
      hypotension on day +15 after second PBSCT, echocardiography was performed which
      revealed a dramatic decrease in systolic function compared to the status pre
      transplant. On the same day acute heart failure with consecutive ventricular
      fibrillation occurred. Although resuscitation was performed immediately the
      patient died. The autopsy revealed massive infiltration by donor CD8-positive
      lymphocytes with concomitant extensive damage of the heart tissue. Acute
      myocarditis of viral origin was excluded by in situ hybridization and nested PCR
      techniques. In this patient, myocardial involvement by acute GVHD seems to have
      triggered a fatal arrhythmia and heart failure.

PMID- 11244448
TI  - Transplantation of CD34-enriched peripheral stem cells from an HLA-haplotype
      mismatched donor to a patient with severe aplastic anemia.
AB  - A 14-year-old girl developed very severe aplastic anemia unresponsive to
      steroids, cyclosporine, ATG and filgrastim. She experienced repeated bacterial
      infections, hypermenorrhagia and epistaxis and received numerous transfusions.
      Lacking a matched family or unrelated donor, she was transplanted 6 months after
      diagnosis with CD34+ cell-enriched peripheral stem cells from her HLA
      haploidentical uncle. Conditioning included fludarabine, cyclophosphamide, 800
      cGy TLI and OKT3. Prompt and sustained trilineage engraftment occurred. Acute
      GVHD grade 1 and herpes esophagitis were successfully treated. Eight months after
      grafting she was well with stable hematopoiesis. She then succumbed to fulminant
      hepatic failure due to adenovirus infection.

PMID- 11244449
TI  - Rapamycin for GVHD prophylaxis--potential for severe myelotoxicity.

PMID- 11244451
TI  - Growth hormone therapy in Prader-Willi syndrome.

PMID- 11244452
TI  - Characterization of a human preadipocyte cell strain with high capacity for
      adipose differentiation.
AB  - OBJECTIVE: To develop and to characterize a human preadipocyte cell strain with
      high capacity for adipose differentiation serving as a model for studying human
      adipocyte development and metabolism in vitro. METHODS: Cells were derived from
      the stromal cells fraction of subcutaneous adipose tissue of an infant with
      Simpson-Golabi-Behmel syndrome (SGBS). Adipose differentiation was induced under
      serum-free culture conditions by exposure to 10 nM insulin, 200 pM
      triiodothyronine, 1 microM cortisol and 2 microM BRL 49653, a PPAR gamma agonist.
      RESULTS: During the differentiation process SGBS cells developed a gene
      expression pattern similar to that found in differentiating human preadipocytes
      with a characteristic increase in fat cell-specific mRNAs encoding lipoprotein
      lipase (LPL), glycero-3-phosphate dehydrogenase (GPDH), GLUT4, leptin and others.
      Differentiated SGBS cells exhibited an increase in glucose uptake upon insulin
      stimulation and in glycerol release upon catecholamine exposure. SGBS adipocytes
      were morphologically, biochemically and functionally identical to in vitro
      differentiated adipocytes from healthy subjects. However, while preadipocytes
      from healthy control infants rapidly lost their capacity to differentiate after a
      few cell divisions in culture, SGBS cells maintained their differentiation
      capacity over many generations: upon appropriate stimulation 95% of SGBS cells of
      generation 30 developed into adipocytes. A mutation in the glypican 3 gene was
      not detected in the patient. Thus, it remains unclear whether the molecular
      alteration in SGBS cells is also responsible for the high differentiation
      capacity and further investigations are required. CONCLUSION: The human cell
      strain described here provides an almost unlimited source of human preadipocytes
      with high capacity for adipose differentiation and may, therefore, represent a
      unique tool for studying human fat cell development and metabolism. International
      Journal of Obesity (2001) 25, 8-15

PMID- 11244453
TI  - The effect of exercise training on beta-adrenergic stimulation of fat metabolism
      in obese men.
AB  - OBJECTIVE: To investigate the in vivo effect of exercise training at high and low
      intensity on beta-adrenergic stimulated fat metabolism in obese men at rest.
      METHOD: Twenty-three obese, healthy subjects were randomly divided in a low
      intensity exercise training program (40% VO(2max), n=7), a high-intensity
      exercise training program (70% VO(2max); n=8), or a non-exercising control group
      (n=8). The exercise training program lasted for 12 weeks with a training
      frequency of 3 times per week. Before and after the intervention body composition
      and maximal aerobic capacity were measured as well as fat metabolism at rest and
      during beta-adrenergic stimulation by isoprenaline. For comparison, six lean
      subjects served as a control group. They participated in a low-intensity exercise
      training program and underwent the same measurements as the obese subjects.
      RESULTS: Relative fat oxidation decreased significantly during infusion of an
      increasing dose of isoprenaline in the obese low-intensity and high-intensity
      exercise training groups as well as in the lean group (P<0.01). Exercise training
      failed to influence the effect of beta-adrenergic stimulation on relative fat
      oxidation in obese men at both intensities and in lean men. In addition, beta
      adrenergic-mediated lipolysis did not seem to be different after low intensity
      exercise training in lean and obese men. Lipolysis might be increased after high
      intensity exercise training in obese men. CONCLUSION: Low- and high-intensity
      exercise training in obese men failed to affect beta-adrenergic mediated relative
      fat oxidation in vivo. beta-Adrenergic-mediated lipolysis might be increased in
      obese men after HI exercise training only. The effect of low-intensity exercise
      training on beta-adrenergic-mediated fat metabolism was similar in lean and obese
      men. International Journal of Obesity (2001) 25, 16-23

PMID- 11244454
TI  - Psychoneuroendocrine characteristics of common obesity clinical subtypes.
AB  - OBJECTIVE: To relate psychological profiles, cerebral asymmetry and the
      hypothalamus-pituitary-adrenal axis (HPA) reactivity to clinical characteristics
      of common obesity. METHODS: Sixty consecutive adult female overweight and obese
      patients attending the outpatient endocrine department were included in this
      study. Clinical evaluation specifically selected a priori the following indexes:
      obesity age of onset, parenthood obesity, carbohydrate craving, binge eating with
      purging, obesity degree (defined by the body mass index (BMI)--weight (kg)/height
      (m(2))), body fat distribution (defined by the abdominal--thigh ratio (A/T)) and
      initial weight loss after medical treatment. Psychological evaluation was
      performed with the Minnesota Multiphasic Personality Inventory (MMPI). In the
      last 30 patients, the Edinburgh Inventory of Manual Preference (EIMP) and the
      corticotrophin-releasing hormone (CRH) test were also performed. RESULTS:
      Clinical characteristics defined a priori were independent variables as evaluated
      by contingency table analysis. Factorial analysis of variance (ANOVA) revealed a
      significantly different MMPI profile, according to parental obesity, with post
      hoc significantly higher scores on the hypochondriasis (Hs), paranoia (Pa),
      psychasthenia (Pt) and schizophrenia (Sc) scales in patients with obese parents.
      Obese patients presented significantly higher dichotomized manual preference
      indexes in relation to overweight patients. Parental obesity, binge eating
      behaviour with purging, body fat distribution and the dichotomized manual
      preference index were independent significant factors for the ACTH response in
      the CRH test, together explaining 41% of the response variability. Age of onset
      of obesity and the dichotomized manual preference index were independent and
      significant factors for the cortisol response, together explaining 37% of its
      variability. A non-normal distribution was found for the ACTH response: high- and
      low-responders presented significantly different MMPI profiles, with high
      responders presenting higher scores on all clinical scales except
      masculinity/femininity (Mf). CONCLUSION: Overweight/obese subjects with parental
      obesity present a distinctive personality profile and a higher ACTH response in
      the CRH test. Cerebral asymmetry may be a relevant factor for obesity development
      and is associated with the HPA reactivity. HPA reactivity is a sensitive index
      integrating clinical, psychological and neural asymmetric factors. International
      Journal of Obesity (2001) 25, 24-32

PMID- 11244455
TI  - The effect of an increased free fatty acid concentration on thermogenesis and
      substrate oxidation in obese and lean men.
AB  - OBJECTIVE: To examine whether a certain increase in plasma free fatty acid (FFA)
      concentration leads to similar increases in lipid oxidation and energy
      expenditure in obese and lean men. DESIGN: The study protocol consisted of a 30
      min baseline period after which subjects received an i.v. bolus of 1000 IE
      heparin. Then consecutive infusions of 4.9, 9.8 and 19.6 microl/kg fat-free mass
      (FFM).min of a lipid heparin mixture were started, each infusion for 30 min.
      SUBJECTS: Eleven obese and 13 lean men with a mean body mass index (BMI) of
      34.2+/-1.0 (+/-s.e.m.) and 23.9+/-0.5 kg/m(2) and age 46.0+/-1.0 and 42.6+/-1.5
      y, respectively. MEASUREMENTS: Energy expenditure, respiratory exchange ratio
      (RER) and carbohydrate and lipid oxidation were continuously measured by indirect
      calorimetry. At the end of each infusion period, a blood sample was taken for
      FFA, glycerol, insulin, beta-hydroxybutyrate, noradrenaline and adrenaline
      determination. RESULTS: At baseline, plasma FFA levels were comparable in both
      groups. Lipid heparin infusion increased plasma FFA concentration by 301+/-47
      micromol/l and 332+/-27 micromol/l in obese and lean men. Energy expenditure
      increased similarly in obese and lean men (0.34+/-0.08 vs 0.40+/-0.08 kJ/min, NS)
      during lipid heparin infusion, whereas RER decreased similarly in both groups.
      Lipid oxidation rates were comparable at baseline and increased similarly in
      obese and lean men (19+/-5 vs 13+/-4 mg/min, NS). Baseline plasma insulin levels
      were higher in the obese, but did not change during lipid heparin infusion.
      Plasma beta-hydroxybutyrate concentrations were similar at baseline, but
      increased significantly less in the obese during lipid heparin infusion. Baseline
      noradrenaline and adrenaline concentrations did not differ significantly between
      groups. During lipid heparin infusion, plasma noradrenaline levels decreased
      significantly, but plasma adrenaline levels remained unchanged in both groups.
      CONCLUSION: A certain increase in plasma FFA concentration leads to similar
      increases in lipid oxidation and energy expenditure in obese and lean men. The
      accumulation of fat in obese subjects may therefore be more likely to be due to a
      defect in adipose tissue lipolysis than a defect in lipid oxidation.
      International Journal of Obesity (2001) 25, 33-38

PMID- 11244456
TI  - Reduced whole-body fat oxidation in women and in the elderly.
AB  - OBJECTIVE: To test the hypothesis that the increase in fat mass observed with
      aging might be related to a decrease in whole-body fat oxidation. SUBJECTS AND
      MEASUREMENTS: Forty volunteers had measurements of sleeping and 24 h substrate
      oxidation in calorimetric chambers, body composition with the (18)O dilution
      technique, VO(2)max, and fiber composition analysis from a biopsy of vastus
      lateralis. They were divided into 10 young women, 10 young men, 10 elderly women
      and 10 elderly men. RESULTS: Sleeping fat oxidation and 24 h fat oxidation were
      lower in women than in men and in elderly than in young participants. Sleeping
      fat oxidation was correlated to fat-free mass and energy balance (multivariate
      analysis). Twenty four hour fat oxidation was correlated to total energy
      expenditure and energy balance (multivariate analysis). After adjustment for
      differences in these factors, sleeping and 24 h fat oxidation were no longer
      different between age and sex groups. None of the parameters of macronutrient
      metabolism was correlated with muscle fiber composition. CONCLUSION: Our data
      suggest that fat oxidation is lower in elderly subjects. This difference could
      favour fat mass gain if fat intake is not adequately reduced. Differences in fat
      free mass and in total energy expenditure appear to participate in the reduction
      in fat oxidation. International Journal of Obesity (2001) 25, 39-44

PMID- 11244457
TI  - What is an optimal diet? Relationship of macronutrient intake to obesity, glucose
      tolerance, lipoprotein cholesterol levels and the metabolic syndrome in the
      Whitehall II study.
AB  - OBJECTIVE: Saturated fats have adverse effects on health. To investigate which is
      more beneficial for energy replacement, we compare the effects of polyunsaturated
      fatty acid and carbohydrate intake on obesity and metabolic variables (fasting
      triglycerides, HDL-cholesterol, LDL-cholesterol and 2 h glucose). Further,
      because the optimum diet may differ according to glucose tolerance, we examine
      the same associations in glucose tolerant and intolerant groups. Finally, we test
      the effect of macronutrient intake on the presence or absence of the metabolic
      syndrome. DESIGN: Cross-sectional analysis. SUBJECTS: A total of 4497 men and
      1865 women aged 39--62 in the Whitehall II study. RESULTS: In men, higher intakes
      of both polyunsaturated fats and carbohydrates were linked to lower waist-hip
      ratio, triglycerides and LDL-cholesterol. Higher carbohydrate intake alone was
      linked to decreased body mass index (for 10 g higher carbohydrate intake, -0.12
      kg/m(2), P<0.0001) and lower HDL-cholesterol (-0.01 mmol/l, P<0.01). In
      normoglycaemic men, higher carbohydrate intakes were associated with higher 2 h
      insulin and glucose levels (0.25 pmol/l, P<0.05 and 0.01 mmol/l, P=0.001,
      respectively). Dietary effects among women were similar, the exception being a
      positive association of polyunsaturated fat intake with body mass index and waist
      -hip ratio (0.47 kg/m(2), P<0.05 and 0.006, P<0.05, respectively). Dietary
      components, with the exceptions of cholesterol and protein in men, were unrelated
      to prevalence of the metabolic syndrome, and adjustment for differences in
      macronutrient intake did not account for the strong inverse association between
      socioeconomic position and the metabolic syndrome. CONCLUSION: Our observational
      data provide evidence that both polyunsaturated fatty acids and carbohydrates
      offer small metabolic benefits with few adverse effects compared with saturated
      fats. International Journal of Obesity (2001) 25, 45-53

PMID- 11244458
TI  - The beta 3-adrenergic receptor gene and obesity in a population sample of African
      Americans.
AB  - OBJECTIVE: To examine the role of the Trp64Arg polymorphism in the beta 3
      adrenergic receptor gene and the beta 3-adrenergic receptor gene locus in obesity
      related traits in African Americans. SUBJECTS: A total of 687 individuals
      representing 193 African American families who were residents of metropolitan
      Chicago. MEASUREMENTS: Genotyping of the Trp64Arg polymorphism in the beta 3
      adrenergic receptor gene and three microsatellite markers flanking the beta 3
      adrenergic receptor gene (ADRB3) locus and measuring various obesity-related
      traits, including body mass index (BMI), fat-free mass, fat mass, percentage fat
      mass, waist circumference and serum lipid levels. RESULTS: The prevalence of
      obesity (defined as body mass index > or = 30 kg/m(2)) in the population was
      27.3% and 51.2% in men and women, respectively. The frequency of the Arg64 allele
      was 10.0%. Multivariate regression analyses confirmed the existence of a
      significant contribution of familial variance to each of the five obesity-related
      traits noted above. Likelihood ratio statistics computed in a multivariate
      regression analysis failed to demonstrate a significant association between the
      Arg64 allele and any of the five obesity-related traits. Single and multipoint
      analyses using extended Haseman--Elston regression analyses failed to demonstrate
      suggestive evidence of linkage of three microsatellite markers that flank the
      beta 3-adrenergic receptor gene to BMI, percentage body fat, waist circumference
      or serum leptin levels. CONCLUSION: Given the contribution of familial variance
      to obesity-related traits in this population, neither the null finding for the
      Arg64 allele nor the lack of evidence of linkage of the ADRB3 locus to obesity
      related traits could be attributed to lack of transmissibility of the traits
      suggesting that neither the Arg64 variant of the beta 3-adrenergic receptor gene
      nor another genetic variant in or near the ADRB3 locus contribute significantly
      to familial aggregation of obesity-related traits in African Americans.
      International Journal of Obesity (2001) 25, 54-60

PMID- 11244459
TI  - Molecular screening of the proopiomelanocortin (POMC ) gene in Italian obese
      children: report of three new mutations.
AB  - BACKGROUND: Although linkage studies strongly suggest that proopiomelanocortin
      (POMC) alterations could play a role in the genetic predisposition to obesity,
      systematic POMC mutational analysis did not completely confirm this hypothesis.
      OBJECTIVES: To verify the presence of mutations of the POMC coding region in
      Italian children with very early onset obesity. SUBJECTS AND METHODS: Eighty
      seven unrelated Italian obese children and adolescents were studied. Mean age at
      obesity onset was 4.7+/-2.5 y. The POMC gene coding region was screened using
      single-strand conformation polymorphism (SSCP) analysis. Bi-directional automatic
      sequencing of PCR products was performed for all individuals who showed an
      aberrant SSCP pattern. RESULTS: Three new mutations have been identified in the
      heterozygous state in three patients: (a) G3834C, resulting in the substitution
      of Ser with Thr at codon 7 within the POMC signal peptide; (b) C3840T, resulting
      in the substitution of Ser with Leu at codon 9 of the pre-proopiomelanocortin
      signal peptide; and (c) C7406G, producing the substitution of Arg with Gly at
      codon 236 within the beta-endorphin peptide. A polymorphism consisting of a 9 bp
      insertion, AGC AGC CGC, between position 6997 and 6998 has been found at the
      heterozygous state in nine patients. They showed leptin levels adjusted for BMI,
      gender and pubertal stage significantly higher than obese subjects homozyous for
      the POMC wild-type allele. CONCLUSIONS: Mutations in codons 7 and 9 of the signal
      peptide may alter the translocation of the pre-proopiomelanocortin into the
      endoplasmic reticulum and, therefore, can be implicated in obesity. Although
      further studies are required, the polymorphism between position 6997 and 6998 may
      represent one of the genetic variations that explain the linkage between obesity
      and POMC. International Journal of Obesity (2001) 25, 61-67

PMID- 11244460
TI  - UCP2 muscle gene transfer modifies mitochondrial membrane potential.
AB  - OBJECTIVE: The aim of this work was to evaluate the effect of uncoupling protein
      2 (UCP2) muscle gene transfer on mitochondrial activity. DESIGN: Five week-old
      male Wistar rats received an intramuscular injection of plasmid pXU1 containing
      UCP2 cDNA in the right tibialis anterior muscles. Left tibialis anterior muscles
      were injected with vehicle as control. Ten days after DNA injection, tibialis
      anterior muscles were dissected and muscle mitochondria isolated and analyzed.
      RESULTS: There were two mitochondrial populations in the muscle after UCP2 gene
      transfer, one of low fluorescence and complexity and the other, showing high
      fluorescence and complexity. UCP2 gene transfer resulted in a 3.6 fold increase
      in muscle UCP2 protein levels compared to control muscles assessed by Western
      blotting. Furthermore, a significant reduction in mitochondria membrane potential
      assessed by spectrofluorometry and flow cytometry was observed. The mitochondria
      membrane potential reduction might account for a decrease in fluorescence of the
      low fluorescence mitochondrial subpopulation. CONCLUSION: It has been
      demonstrated that UCP2 muscle gene transfer in vivo is associated with a lower
      mitochondria membrane potential. Our results suggest the potential involvement of
      UCP2 in uncoupling respiration. International Journal of Obesity (2001) 25, 68-74

PMID- 11244461
TI  - Characterization of mouse GBP28 and its induction by exposure to cold.
AB  - OBJECTIVE: To investigate whether the expression of the novel adipose tissue
      specific protein GBP28 in adipose tissue and serum are altered in mice under a
      variety of conditions. DESIGN: Mice were fed a high-fat diet for 4 weeks, fasted
      for 48 h or exposed at 4 degrees C. SUBJECTS: C57BL/6J mouse, male, 4--6 weeks
      old. MEASUREMENTS: GBP28 mRNA, GBP28 protein, blood glucose, insulin and fad pad
      weight of the mice. RESULTS: We first confirmed that the mouse has GBP28 and its
      characteristics are the same as human GBP28. Serum concentration and mRNA levels
      of GBP28 significantly increased in the mice exposed to cold. CONCLUSION: GBP28
      may play a role in homeostasis, regulating body temperature and basal metabolic
      rate in response to changing environmental conditions. International Journal of
      Obesity (2001) 25, 75-83

PMID- 11244462
TI  - Reduced food intake in response to CGP 71683A may be due to mechanisms other than
      NPY Y5 receptor blockade.
AB  - INTRODUCTION: The purpose of this study was to test the continuing validity of
      the hypothesis that neuropeptide Y (NPY) produced in the brain controls food
      intake through an interaction with the NPY Y(5) receptor subtype. METHODS: The
      hypothesis was tested using CGP 71683A a potent and highly selective non-peptide
      antagonist of the NPY Y(5) receptor which was administered into the right lateral
      ventricle of obese Zucker fa/fa rats. RESULTS: Intraventricular injection of 3.4
      nmol/kg NPY increased food intake during a 2 h test period. Doses of CGP 71683A
      in excess of 15 nmol/kg (i.cv.) resulted in blockade of the increase in food
      intake produced by NPY. Repeated daily injection of CGP 71683A (30--300 nmol/kg,
      i.cv.) immediately before the dark phase produced a dose-dependent and slowly
      developing decrease in food intake. CGP 71683A has a low affinity for NPY Y(1),
      Y(2) and Y(4) receptors but a very high affinity for the NPY Y(5) receptor (Ki,
      1.4 nM). Surprisingly, CGP 71683A had similarly high affinity for muscarinic
      receptors (Ki, 2.7 nM) and for the serotonin uptake recognition site (Ki, 6.2 nM)
      in rat brain. Anatomic analysis of the brain after treatment with CGP 71683A
      demonstrated an inflammatory response associated with the fall in food intake.
      CONCLUSIONS: While the fall in food intake in response to CGP 71683A may have a
      Y(5) component, interactions with other receptors or inflammatory mediators may
      also play a role. It is concluded that CGP 71683A is an imprecise tool for
      investigating the role of the NPY Y(5) receptor in the control of physiological
      processes including food intake. International Journal of Obesity (2001) 25, 84
      94

PMID- 11244463
TI  - Restoration of fertility in young obese (Lep(ob) Lep(ob)) male mice with low dose
      recombinant mouse leptin treatment.
AB  - OBJECTIVE: We investigated the effects of low-dose leptin treatment on
      restoration of fertility in young adult male leptin deficient obese mice.
      EXPERIMENTAL DESIGN AND RESULTS: MMTV-TGF-alpha Lep(ob) Lep(ob) mice (8--10 weeks
      old) were treated with recombinant mouse leptin. In experiment 1, four mice (5
      microg/g body weight leptin followed by 2.5 microg/g) lost weight and impregnated
      females (number of pregnancies/number of females, 3/6, 5/6, 5/10, 4/10). In
      experiment 2, Leptin-Obese (2.5 microg/g) and Control-Lean mice weighed
      significantly less than Control-Obese mice. Epididymal pad weights of Control
      Obese mice were the heaviest, followed by those of Leptin-Obese mice, and Control
      Lean mice were the lightest. Testes weight was greater in Control-Lean vs Control
      Obese mice. Leptin-Obese mice had testes weight not significantly different from
      either control group. Four of five Leptin-Obese mice impregnated females (4/10,
      5/10, 2/10, 5/12, 0/10). CONCLUSIONS: These results indicate that low-dosage
      mouse recombinant leptin treatment restored fertility to young Lep(ob) Lep(ob)
      male mice. Although body weights of Leptin-Obese mice were similar to those of
      lean age-matched mice, epididymal fat pad weights were heavier. International
      Journal of Obesity (2001) 25, 95-97

PMID- 11244464
TI  - A strong association between biologically active testosterone and leptin in non
      obese men and women is lost with increasing (central) adiposity.
AB  - OBJECTIVE: In both humans and rodents, males have lower levels of leptin than
      females at any level of adiposity. Experimental data support the idea that
      testosterone exerts a negative influence on leptin levels. There are, however,
      major inconsistencies in available data concerning the possible association
      between androgenicity and leptin in humans. Reasons could be the influence of
      androgenicity on leptin production being dependent on body composition, and
      incomplete measures of biologically active testosterone levels. In the present
      study we have characterized the relationship between biologically active
      testosterone and leptin after careful stratification for gender and adiposity.
      DESIGN AND SUBJECTS: Healthy subjects (n=158; 85 men and 73 pre- and
      postmenopausal women) from the Northern Sweden MONICA (Monitoring of Trends and
      Determinants in Cardiovascular Disease) population were studied with a cross
      sectional design. MEASUREMENTS: Anthropometric measurements (body mass index
      (BMI) and waist circumference) and oral glucose tolerance tests were performed.
      Circulating levels of leptin, insulin, testosterone, androstenedione, sex hormone
      binding globulin (SHBG) and insulin-like growth factor-1 (IGF-1) were measured by
      radioimmunoassays or microparticle enzyme immunoassays. Apparent concentrations
      of free testosterone and non-SHBG-bound testosterone were calculated. RESULTS:
      After adjustments for age, BMI and insulin, leptin levels were inversely
      correlated to testosterone levels in non-obese men (r=-0.56, P<0.01) and obese
      women (r=-0.48, P<0.05). In contrast, leptin and testosterone correlated in a
      positive manner in non-obese women (r=0.59, P<0.01). Levels of SHBG were
      negatively associated with leptin in men with low waist circumference (r=-0.59,
      P<0.01). The following factors were associated with leptin in a multivariate
      model: low levels of biologically active testosterone and SHBG in men with low
      and medium waist circumference, insulin in men with high waist circumference,
      high levels of testosterone and insulin in non-obese women, and BMI in obese
      women. CONCLUSION: We conclude that low leptin levels are associated with
      androgenicity in non-obese men and women and that the direction of this
      association is dependent on gender and body fat distribution. Based on these
      results we suggest that the relation between testosterone and leptin contributes
      to the gender difference in circulating leptin levels. International Journal of
      Obesity (2001) 25, 98-105

PMID- 11244465
TI  - Dietary and lifestyle factors in relation to plasma leptin concentrations among
      normal weight and overweight men.
AB  - OBJECTIVE: Leptin, the product of the obesity (ob) gene, is a multi-functional
      polypeptide that is important in energy metabolism, which is strongly correlated
      with body fat mass and body mass index (BMI). In a recent prospective study, we
      found that leptin was positively associated with 4 y weight gain among overweight
      and obese men. This suggests that leptin resistance, marked by hyperleptinemia
      among obese subjects, may be an important marker for weight gain. The purpose of
      this study is to evaluate whether modifiable dietary and lifestyle factors are
      associated with plasma leptin concentrations among US men. METHODS: We included
      268 men aged 47--83 y (who were free of cardiovascular disease, diabetes mellitus
      and cancer, except nonmelanoma skin cancer) from the ongoing Health Professionals
      Follow-up Study. These subjects completed a detailed dietary and lifestyle
      questionnaire (including cigarette smoking, alcohol drinking and physical
      activity) and provided a fasting venous blood sample in 1994. All blood samples
      were stored in a deep freeze (-70 degrees C) for 4--5 y before being analyzed.
      Plasma leptin concentrations were measured by radioimmunoassay. RESULTS: Men in
      the highest quintile of plasma leptin (mean=14.4 ng/ml) weighed more, were less
      physically active, and had higher total and saturated fat and cholesterol intake
      than men in the lowest quintile (mean=3.0 ng/ml). Physical activity and current
      smoking were inversely associated with plasma leptin concentrations (P<0.001). A
      20 MET difference in physical activity per week (equivalent to approximately 3 h
      of jogging) was associated with 0.38--0.58 ng/ml lower plasma leptin
      concentrations for normal weight and overweight men after adjusting for total
      energy and fat intake, BMI and other confounding variables. Total fat and
      monounsaturated fat intakes were positively associated with plasma leptin
      concentrations even after adjusting for BMI and other confounding variables;
      however, this association was limited to men of normal weight (BMI<25 kg/m(2)).
      CONCLUSION: These data suggest that physical activity may be a significant
      determinant of plasma leptin concentrations in men. Increasing physical activity
      is associated with lower plasma leptin concentrations even after adjusting for
      BMI. Physical activity may lower leptin concentrations not only due to decreased
      body fat mass, but potentially through an increase in leptin sensitivity.
      International Journal of Obesity (2001) 25, 106-114

PMID- 11244466
TI  - Dissociation of leptin and body weight in hyperthyroid patients after radioiodine
      treatment.
AB  - OBJECTIVE: Leptin regulates energy production rates and body weight, which are
      frequently altered in hyperthyroidism. Data on a possible interaction between
      leptin and thyroid hormones are controversial. We assessed leptin serum
      concentrations, BMI, proportional fat tissue mass and thyroid hormones in
      hyperthyroid patients in a long-term follow-up after radioiodine therapy. DESIGN:
      The study included 28 hyperthyroid patients (mean age 66 y) before and up to one
      y after radioiodine therapy. Leptin and thyroid hormones, general parameters,
      BMI, proportional fat tissue (PFT) measurements by DEXA and thyroid morphology
      were recorded. Twenty-four age-matched euthyroid individuals (mean age 63 y)
      served as controls. RESULTS: At baseline, leptin concentrations were
      significantly decreased in all hyperthyroid patients as compared to controls. One
      year after radioiodine therapy, 71% of the patients were euthyroid (group A) and
      29% remained hyperthyroid (group B). BMI and PFT increased in both groups. While
      leptin concentrations remained low in group B, they normalised in group A after 6
      to 12 months. Changes in leptin and thyroid hormone concentrations were
      positively correlated in group A patients (r=0.49, P=0.03) but not in patients
      remaining hyperthyroid. CONCLUSION: Our data indicate a dissociation in the
      regulation of plasma leptin and BMI as well as proportional fat tissue in
      hyperthyroid patients which may be attributable to differences in lean and
      adipose mass weight gain after radioiodine therapy or direct influences of
      thyroid hormones on leptin regulation. International Journal of Obesity (2001)
      25, 115-120

PMID- 11244467
TI  - Leptin concentrations in relation to overall adiposity, fat distribution, and
      blood pressure in a rural Chinese population.
AB  - OBJECTIVE: To examine the associations between leptin levels and body mass index
      (BMI), fat distribution (reflected by waist to hip ratio and skinfold
      measurements), and blood pressure in a rural Chinese population. DESIGN AND
      SUBJECTS: A cross-sectional study of 294 participants who provided blood samples.
      MEASUREMENTS: Plasma concentrations of leptin, BMI, waist to hip ratio, skinfold
      thickness, and blood pressure. RESULTS: The average leptin concentration was 5.2
      microg/l (3.1 for men and 7.3 for women). In univariate analyses, leptin levels
      were significantly correlated with BMI (r=0.47), abdominal skinfold thickness
      (r=0.53), triceps skinfold thickness (r=0.56), waist circumference (r=0.41), hip
      circumference (r=0.51), waist to hip ratio (r=0.17), and diastolic blood pressure
      (r=0.13). In multivariate analyses controlling for age, sex, education, current
      smoking, and alcohol use, independent associations between leptin levels and BMI,
      waist to hip ratio, waist circumference, and abdominal skinfold thickness
      remained. However, the significant association between leptin and blood pressure
      disappeared after adjusting for BMI, whereas the association between BMI and
      blood pressure persisted after adjusting for leptin level. CONCLUSIONS: We
      observed a strong positive relationship between overall adiposity and leptin
      levels in both men and women in a rural Chinese population. In addition, leptin
      concentrations were significantly associated with central obesity measured by
      waist to hip ratio and abdominal skinfold, independent of overall obesity. The
      observed positive association between leptin and blood pressure was largely
      explained by BMI. International Journal of Obesity (2001) 25, 121-125

PMID- 11244468
TI  - Leptin and other components of the Metabolic Syndrome in Mauritius--a factor
      analysis.
AB  - OBJECTIVE: To use factor analysis to examine the putative role of leptin in the
      Metabolic Syndrome, and to define better the associations among observed
      variables and the identified factors. DESIGN: Factor analysis of cross-sectional
      data from a 1987 survey. SUBJECTS: Non-diabetic residents of Mauritius who
      participated in population-based surveys in 1987 and 1992 (1414 men and 1654
      women). MEASUREMENTS: Fasting and 2 h plasma glucose and insulin following a 75 g
      oral glucose load; seated blood pressure; body mass index (BMI); waist-to-hip
      ratio (WHR); and fasting serum triglycerides, HDL-cholesterol, leptin and uric
      acid concentrations. RESULTS: Principal components factor analysis revealed three
      factors for men and women that explained between 54 and 55% of the observed
      variance of the 12 measured variables. General features of these factors were as
      follows: factor 1, WHR, BMI, leptin, fasting and 2 h insulin, triglycerides, and
      HDL-cholesterol; factor 2, systolic and diastolic blood pressure, uric acid (men
      only), and fasting glucose (women only); and factor 3, fasting and 2 h glucose
      and insulin. Only three variables loaded on more than one factor with a loading >
      or = 0.4 (fasting and 2 h insulin, fasting glucose in women only). Leptin loaded
      on one factor only in both men and women. CONCLUSIONS: Since multiple factors
      underlie the Metabolic Syndrome, and since no observed variable loads on all
      three factors, more than one mechanism might account for the observed clustering
      of risk characteristics. Leptin does not unite features of this syndrome due to
      its loading on one factor only. Uric acid is related to a different factor in men
      and women. The absence of gender differences in factor loadings argues for
      similar mechanisms for the Metabolic Syndrome in men and women in Mauritius.
      International Journal of Obesity (2001) 25, 126-131

PMID- 11244469
TI  - Heritability of leptin levels and the shared genetic effects on body mass index
      and leptin in adult Finnish twins.
AB  - OBJECTIVES: Leptin is involved in the regulation of body weight, but the relative
      role of genetic and environmental influences on inter-individual variation in
      leptin levels is unknown. DESIGN AND SUBJECTS: To investigate the genetic and
      environmental contributions to the association of body mass index (BMI) with
      serum leptin levels, 58 monozygotic (MZ, 27M, 31F), and 74 like-sexed dizygotic
      (DZ, 32M, 42F) Finnish twin pairs aged 50--76 y were studied. MEASUREMENTS: Serum
      leptin levels, weight, height, hip and waist measurements. RESULTS: Women had
      higher mean leptin levels (16.8+/-9.5 ng/ml), and more overall variability in
      leptin levels than men (6.4+/-3.5 ng/ml; P<0.0001). Leptin levels correlated
      highly with BMI in men and women. Among women, the MZ and DZ pairwise
      correlations for leptin were 0.41 (P=0.009) and 0.07 (P=0.32), respectively.
      Among men the MZ and DZ pairwise correlations for leptin were 0.47 (P=0.006) and
      0.23 (P=0.10). Univariate twin analysis indicated that, among women, 34% and,
      among men, 45% of the variance in leptin can be attributed to additive genetic
      effects, and the remainder to unique environmental effects. Significant non
      additive genetic or shared familial effects could not be demonstrated. A
      bivariate twin analysis of leptin and BMI indicated that the correlation between
      additive genetic effects on leptin and BMI was 0.79 (95% CI 0.68--0.86) in women,
      and 0.68 (0.51--0.80) in men. The correlation between environmental effects on
      leptin and BMI was 0.77 (95% CI 0.66--0.85) in women, and 0.48 (0.26--0.66) in
      men. CONCLUSION: Leptin levels are moderately heritable in older adults, and a
      substantial proportion of genetic effects are in common on leptin levels and
      obesity in both women and men. International Journal of Obesity (2001) 25, 132
      137

PMID- 11244470
TI  - Acute stimulation of leptin concentrations in humans during hyperglycemic
      hyperinsulinemia. Influence of free fatty acids and fasting.
AB  - OBJECTIVE: To assess the acute regulation of leptin concentrations by insulin,
      glucose and free fatty acids (FFAs). DESIGN: Four protocols: saline control
      experiment (CON); hyperglycemic clamps (approximately 8.3 mmol/l, 120 min) after
      an overnight fast (12 FAST); after a 36 h fast (36 FAST); and after a 36 h fast
      during which Intralipid/heparin was given over the last 24 h (36 FAST+FFA).
      SUBJECTS: Lean, young, healthy volunteers; control group (n=6), experimental
      group (n=6). MEASUREMENTS: Serum leptin concentrations. RESULTS: Glucose and
      insulin concentrations were similar during the three clamp protocols. Average
      FFAs during the last 60 min of the clamp were 671+/-68 microM (CON),109+/-15
      microM (12 FAST), 484+/-97 microM (36 FAST) and 1762+/-213 microM (36 FAST+FFA).
      Leptin concentrations decreased similarly during 36 FAST and 36 FAST+FFA. Leptin
      concentrations at 120 min (expressed as percentage of mean basal value) were
      0.82+/-0.02 (CON), 0.93+/-0.08 (12 FAST) (P=0.29), 1.19+/-0.06 (36 FAST) (P<0.01)
      and 1.44+/-0.12 (36 FAST+FFA) (P<0.01). CONCLUSION: During a one-day fast leptin
      concentrations decrease regardless of maintainance of an isocaloric balance.
      During acute hyperinsulinemic hyperglycemia leptin concentrations increase only
      after a preceding fast. This increase was most pronounced during simultaneous
      elevation of FFAs. Overall, our findings are compatible with the hypothesis that
      leptin secretion may be coupled to triglyceride synthesis rather than to the
      absolute lipid content of the adipocyte. International Journal of Obesity (2001)
      25, 138-142

PMID- 11244471
TI  - Increased adiposity due to viral infection in animals.

PMID- 11244476
TI  - Ser9Gly dopamine D3 receptor polymorphism and spontaneous dyskinesia in never
      medicated schizophrenic patients.

PMID- 11244477
TI  - DRD4 and DAT1 as modifying genes in alcoholism: interaction with novelty seeking
      on level of alcohol consumption.

PMID- 11244478
TI  - Association of a functional 5-HT transporter gene polymorphism with anorexia
      nervosa and food intake.

PMID- 11244479
TI  - Major corrections are indicated for 'Comparative proteome analysis of the
      hippocampus implicates chromosome 6q in schizophrenia'.

PMID- 11244481
TI  - The amygdala: vigilance and emotion.
AB  - Here we provide a review of the animal and human literature concerning the role
      of the amygdala in fear conditioning, considering its potential influence over
      autonomic and hormonal changes, motor behavior and attentional processes. A
      stimulus that predicts an aversive outcome will change neural transmission in the
      amygdala to produce the somatic, autonomic and endocrine signs of fear, as well
      as increased attention to that stimulus. It is now clear that the amygdala is
      also involved in learning about positively valenced stimuli as well as spatial
      and motor learning and this review strives to integrate this additional
      information. A review of available studies examining the human amygdala covers
      both lesion and electrical stimulation studies as well as the most recent
      functional neuroimaging studies. Where appropriate, we attempt to integrate basic
      information on normal amygdala function with our current understanding of
      psychiatric disorders, including pathological anxiety.

PMID- 11244482
TI  - Association between Novelty Seeking and the -521 C/T polymorphism in the promoter
      region of the DRD4 gene.
AB  - Association between the human personality trait 'Novelty Seeking' and the
      polymorphism of the DRD4 gene was first reported by Ebstein and Benjamin in 1996.
      This was soon followed by replication studies in various ethnic groups and by
      studying the role of other neurotransmitter receptor and transporter genes in the
      genetic determination of human temperament. More recently, several polymorphic
      sites of the upstream regulatory region of the DRD4 gene have been described.
      Among these the -521 C/T single nucleotide polymorphism (SNP) was shown to be
      associated with the Novelty Seeking (NS) scores of the Temperament and Character
      Inventory (TCI) in a Japanese male population. We have investigated the -521 C/T
      SNP polymorphism in a Caucasian (Hungarian) population, and here we report a
      replication of the Japanese findings, in an association study involving 109
      healthy Hungarian volunteers. We found a weak association between NS and CC vs CT
      or TT genotypes (P < 0.06). Examination of this relation in male and female sex
      groups, however, strengthened the association for females (P < 0.01), but showed
      no genotypic effect for males.

PMID- 11244483
TI  - Mutation screening of the Wolfram syndrome gene in psychiatric patients.
AB  - Wolfram syndrome, a rare autosomal recessive neurodegenerative disorder, was
      originally described as a combination of familial juvenile-onset diabetes
      mellitus and optic atrophy. It was later demonstrated that Wolfram syndrome
      patients were highly prone to psychiatric disorders. Mutations in exon 8 of the
      Wolfram syndrome gene account for 88% of the patients with Wolfram syndrome. To
      examine whether the gene responsible for causing Wolfram syndrome is involved in
      psychiatric disorders, we screened exon 8 of the Wolfram syndrome gene for
      mutations in 119 patients with schizophrenia, one patient with schizoaffective
      disorder, 12 patients with bipolar disorder and 15 patients with major
      depression, using sequence analysis. In Wolfram syndrome patients, this gene has
      been shown to have primarily nonsense or frameshift mutations, which would result
      in a premature truncation of the protein. None of the psychiatric patients
      screened in this study carried these types of mutations. We identified, however,
      24 new variations whose significance remains to be determined.

PMID- 11244484
TI  - Protein kinase A and Rap1 levels in platelets of untreated patients with major
      depression.
AB  - We have recently reported altered levels of protein kinase A and Rap1 in patients
      with bipolar disorder. The purpose of the current investigation was to assess the
      levels of these proteins in platelets from untreated euthymic and depressed
      patients with major unipolar depression. Platelets were collected from 45 drug
      free unipolar patients (13 euthymic and 32 depressed) and 45 healthy subjects.
      The levels of protein kinase A and Rap1 were assessed by Western blot analysis,
      immunostaining and computer-assisted imaging. The immunolabeling of the
      regulatory subunit type II of protein kinase A and that of Rap1 was significantly
      lower in untreated depressed patients compared with untreated euthymic patients
      and healthy subjects. No significant differences were found in the immunolabeling
      of both the regulatory type I and the catalytic subunits of protein kinase A
      among groups. Levels of the regulatory subunit type II of protein kinase A and
      Rap1 are altered in platelets of unipolar depressive patients. These findings may
      provide new insight about the relationship between components of cAMP signaling
      and affective disorders.

PMID- 11244485
TI  - Single nucleotide polymorphisms distinguish multiple dopamine transporter alleles
      in primates: implications for association with attention deficit hyperactivity
      disorder and other neuropsychiatric disorders.
AB  - The human dopamine transporter (DAT) gene contains a variable number tandem
      repeat (VNTR; 40 bases/3 to >11 repeats) in the 3'-untranslated region (3'-UTR),
      resulting in multiple alleles categorized by length. The 10-copy allele has been
      associated with attention deficit hyperactivity disorder (ADHD), yet it accounts
      for only a small proportion of symptom variance. We investigated whether the
      rhesus monkey DAT gene contains a repeat sequence similar to the human and
      whether this region differs in the five most hyperactive and the five most sedate
      animals selected from a behaviorally characterized cohort (n = 22). A fixed
      number tandem repeat (FNTR; 39 bases/12 repeats) was observed in all animals.
      Accordingly, this FNTR is unbefitting an association of DAT transcript length
      with hyperactivity. However, sequence analysis revealed potential single
      nucleotide polymorphisms (SNPs), one of which affects a Bst1107I restriction
      site. We screened the entire cohort, confirmed that all the rhesus monkeys had
      repeat regions of the same length, and demonstrated that digestion with Bst1107I
      was sufficient to distinguish two distinct FNTR alleles. Bst1107I genotype was
      suggestive but not predictive of hyperactive behavior. Based on these data, we
      speculated that SNPs may exist in human DAT VNTR alleles. To support this
      hypothesis, we cloned a portion of a novel 10-repeat allele from the human gene
      containing an SNP that abolishes a DraI restriction site. We conclude that SNPs
      create a diversity of DAT alleles between individuals that may be greater than
      previously identified based solely on the length of the VNTR region, and that
      alleles of specific sequence may contribute to dopamine-related disorders.

PMID- 11244486
TI  - No association or linkage between polymorphisms in the genes encoding
      cholecystokinin and the cholecystokinin B receptor and panic disorder.
AB  - Growing animal data implicate cholecystokinin in the regulation of anxiety, while
      human clinical research confirms the role of cholecystokinin in the provocation
      of panic attacks. Antipanic medications suppress the ability of cholecystokinin
      to induce panic attacks, and may alter the expression of the cholecystokinin
      gene. Thus, there is increased interest in understanding the molecular genetic
      component of these observations. Recent association studies using persons with
      panic disorder described some association between polymorphisms in the genes
      encoding cholecystokinin and the cholecystokinin B-receptor and panic disorder.
      In this study, we used a family-based design, employing 596 individuals in 70
      panic disorder pedigrees, as well as 77 haplotype relative risk 'triads'.
      Subjects were genotyped for two polymorphisms: the polymorphic microsatellite
      marker in the CCK-BR locus using PCR-based genotyping and at a single nucleotide
      polymorphism in the CCK promoter using a fluorescence polarization detection
      assay, and the data were analyzed for genetic association and linkage. Employing
      a variety of diagnostic and genetic models, linkage analysis produced no
      significant lod scores at either locus. Family-based tests of association, the
      haplotype-based haplotype relative risk statistic and the transmission
      disequilibrium test, were likewise non-significant. The results reported here
      provide little support for the role of these polymorphisms in panic disorder.

PMID- 11244487
TI  - Evidence that the activities of erythrocyte free radical scavenging enzymes and
      the products of lipid peroxidation are increased in different forms of
      schizophrenia.
AB  - In order to examine antioxidant status and lipid peroxidation in schizophrenia
      patients, activities of three free radical scavenging enzymes (superoxide
      dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)), and the
      level of thiobarbituric acid-reactive substances (TBARS) as an index of lipid
      peroxidation have been studied in red blood cells. Schizophrenic patients were
      divided into three groups (disorganized (n = 21), paranoid (n = 26) and residual
      types (n = 18)) to determine differences between subgroups. SOD, CAT and GSH-Px
      activities in the control group were found to be 1461.0 +/- 248.6 U g(-1) Hb,
      148.2 +/- 59.3 k g(-1) Hb and 25.87 +/- 4.25 U g(-1) Hb, respectively. We found
      no significant differences in SOD activities between study and control groups.
      There was a significant increase in SOD activity in the residual group compared
      to the paranoid group (P < 0.005). CAT activity was found to be increased in
      disorganized (148%), paranoid (147%), and residual (165%) groups compared to the
      control group. GSH-Px activity was markedly increased in the study groups except
      the paranoid group. Statistically significant (3-4 fold) increases in TBARS
      levels of red blood cells were found in all the study groups. It is proposed that
      antioxidant status may be changed in schizophrenia and thus may induce lipid
      peroxidation. Therefore, oxidative stress may have a pathophysiological role in
      all the subtypes of schizophrenia.

PMID- 11244488
TI  - Lack of evidence to support the association of the human prion gene with
      schizophrenia.
AB  - Recently a new variant of Creutzfeldt-Jakob disease, a human prion disease, with
      prominent psychiatric manifestations in the early stage was identified,
      suggesting that human prion disease may be associated with mental disorders.
      Furthermore, a novel missense mutation with asparagine-to-serine substitution at
      codon 171 of the human prion gene (N171S) was identified in a family with severe
      psychiatric symptoms. This finding provides further clue that the prion gene may
      be a susceptibility gene for certain psychiatric disorders. We systematically
      sequenced the protein-coding and untranslated exons of prion gene in 62 Han
      Chinese schizophrenic patients with positive family history from Taiwan. We
      identified two polymorphisms that alter amino acid sequences, a methionine/valine
      at codon 129 (M129V) and a glutamate/lysine at codon 219 (E219K), respectively.
      Further comparison of the genotype, allele and haplotype frequency distributions
      of these two polymorphisms between 234 schizophrenic patients and 100 non
      psychotic controls, however, did not reveal significant differences between two
      groups. Besides, no other mutations in the prion gene were identified in these 62
      patients. Hence, our results suggest that the prion gene may not play a major
      role in conferring susceptibility to schizophrenia.

PMID- 11244489
TI  - Association between -G308A tumor necrosis factor alpha gene polymorphism and
      schizophrenia.
AB  - Dysregulation of the inflammatory response system has been linked to
      pathophysiology of schizophrenia. Evidence of immune activation has derived from
      the detection of abnormal levels of proinflammatory cytokines and their receptors
      in peripheral blood and cerebrospinal fluid from schizophrenic patients.
      Cytokines are involved in normal CNS development as well as in the pathogenesis
      of many neuro-psychiatric disorders, acting directly on neural cells or
      modulating neurotransmitter and neuropeptide systems. In particular tumor
      necrosis factor alpha (TNFalpha), depending on its concentration, can exert both
      neurotrophic and neurotoxic effects and influence neural cell growth and
      proliferation. Moreover, TNFalpha gene is located on the small arm of chromosome
      6 (6p21.1-21.3), a locus associated with genetic susceptibility to schizophrenia.
      We studied the distribution of -G308A TNFalpha gene polymorphism in 84
      schizophrenic patients and in 138 healthy volunteers. This biallelic base
      exchange polymorphism directly affects TNFalpha plasma levels. Frequency of the
      TNF2(A) allele is significantly increased in schizophrenic patients as compared
      to controls (P = 0.0042). Genotype distribution is also significantly different
      (P = 0.0024). TNF2 homozygotes are represented only in the patient group (P =
      0.002). These data suggest a potential role of TNFalpha as a candidate gene for
      susceptibility to schizophrenia and suggest that immune dysregulation in
      schizophrenic patients could also have a genetic component.

PMID- 11244490
TI  - A novel polymorphism of the brain-derived neurotrophic factor (BDNF) gene
      associated with late-onset Alzheimer's disease.
AB  - Several lines of evidence have suggested altered functions of the brain-derived
      neurotrophic factor (BDNF) in the pathogenesis of neurodegenerative diseases
      including Alzheimer's disease (AD). In the search for polymorphisms in the 5'
      flanking and 5'-noncoding regions of the BDNF gene, we found a novel nucleotide
      substitution (C270T) in the noncoding region. We performed an association study
      between this polymorphism and AD in a Japanese sample of 170 patients with
      sporadic AD (51 early-onset and 119 late-onset) and 498 controls. The frequency
      of individuals who carried the mutated type (T270) was significantly more common
      in patients with late-onset AD than in controls (P = 0.00004, odds ratio: 3.8,
      95% CI 1.9-7.4). However, there was no significant difference in the genotype
      distribution between the patients with early-onset AD and the controls, although
      this might be due to the small sample size of the early-onset group. Our results
      suggest that the C270T polymorphism of the BDNF gene or other unknown
      polymorphisms, which are in linkage disequilibrium, give susceptibility to late
      onset AD. We obtained no evidence for the possible interactions between the BDNF
      and apolipoprotein E (APOE) genes, suggesting that the possible effect of the
      BDNF gene on the development of late-onset AD might be independent of the APOE
      genotype.

PMID- 11244491
TI  - Human homolog of the mouse imprinted gene Impact resides at the pericentric
      region of chromosome 18 within the critical region for bipolar affective
      disorder.
AB  - Several mapping studies of families with multiple individuals who have bipolar
      affective disorder (BPAD) have demonstrated possible linkage of the trait to the
      pericentric region of chromosome 18 (18cen). Currently, the large size of the
      critical interval defined by these studies makes effective selection of candidate
      genes formidable. However, documentation of 18cen-linked families in which a
      parent-of-origin effect was observed in the transmission of the BPAD trait
      provides a clue to the nature of the putative gene; it may be imprinted. In the
      present study, we cloned IMPACT, the human homolog of the mouse imprinted gene
      Impact and mapped it to 18cen within the critical interval for BPAD. Human IMPACT
      encodes a protein with 320 amino acids and is expressed at high levels in the
      brain. Since only a small number of imprinted genes are estimated to be present
      in the entire genome, very few imprinted genes would be expected to be present in
      this particular chromosomal region. Hence, IMPACT represents a candidate gene for
      BPAD susceptibility. Alternatively, other as yet unknown imprinted gene(s)
      adjacent to IMPACT could contribute to the BPAD trait, since multiple imprinted
      genes may occasionally form clusters. Localization of human IMPACT at 18cen in
      this study defines a promising target region in which to search for putative BPAD
      genes.

PMID- 11244492
TI  - Exclusion of the Darier's disease gene, ATP2A2, as a common susceptibility gene
      for bipolar disorder.
AB  - Bipolar affective disorder is a genetically complex psychiatric disorder with a
      population prevalence of approximately 1%. We have previously reported
      cosegregation of bipolar affective disorder and Darier's disease, a dominant skin
      disorder with a neuropsychiatric component. The gene for Darier's disease was
      mapped to chromosome 12q23-q24.1 and linkage studies by us and others have
      subsequently implicated this region as harbouring a susceptibility gene for
      bipolar affective disorder. In this study we have investigated the Darier's
      disease gene ATP2A2, the calcium pumping ATPase SERCA2, as a potential
      susceptibility gene for bipolar disorder under the hypothesis that variations in
      SERCA2 have pleiotropic effects in brain. Support for this hypothesis comes from
      clinical evidence of neuropsychiatric abnormalities in Darier's disease, genetic
      data produced in our study showing non-random clustering of missense mutations in
      ATP2A2 in neuropsychiatric Darier patients, and functional data demonstrating the
      role of SERCA2 in intracellular calcium regulation. In a panel of 15 unrelated
      bipolar patients from multiply affected families showing increased allele sharing
      at markers in the 12q23-q24.1 region, we performed mutational screening of the
      ATP2A2 coding sequence, promoter regions, and 3' untranslated region and
      identified six sequence variations. These were analysed in a large sample of
      bipolar patients (n = 324) and control subjects (n = 327). Analysis of allele and
      genotype distributions for all six variations, and of haplotype frequencies
      showed no evidence for the involvement of ATP2A2 in producing susceptibility to
      bipolar disorder.

PMID- 11244493
TI  - TPH and suicidal behavior: a study in suicide completers.
AB  - An association between the gene that codes for tryptophan hydroxylase (TPH)-the
      rate-limiting enzyme in the synthesis of serotonin-and suicidal behavior has been
      investigated with some detail in samples of living subjects who attempted
      suicide. In this study, we investigated TPH and suicide completion, the most
      severe form of suicidal behavior. A relatively large sample of suicide completers
      (n = 101) was genotyped at three TPH loci (two polymorphisms in the promoter
      region, A-6526G and G-5806T, and one in intron 7, A218C) and compared to
      psychiatrically normal living controls (n = 129). Although no significant
      differences were found between groups for genetic variation at single loci,
      haplotype analysis revealed that one haplotype (-6526G -5806T 218C) was
      significantly more frequent among suicide cases than in normal controls (chi(2) =
      11.30, df = 2, P = 0.0008; OR = 2.0 CI: 1.30-3.6). Further analyses suggested
      that this haplotype is particularly more frequent among subjects who committed
      suicide using violent methods. Similar results were observed in recent haplotype
      analyses in suicide attempters, which found that the equivalent of haplotype 
      6526G -5806T 218C was more frequent in impulsive attempters (Rotondo et al, Mol
      Psychiatry 1999; 4: 360-368). Our results replicate in suicide completers
      previous data observed in suicide attempters. These and other results continue to
      point to the substantial role that the gene that codes for TPH may play in the
      neurobiology of suicidal behavior.

PMID- 11244494
TI  - Differential expression of diacylglycerol kinase iota and L18A mRNAs in the
      brains of alcohol-preferring AA and alcohol-avoiding ANA rats.
AB  - Ethanol preference and behavioral disinhibition in AA (alcohol accepting) animals
      is a behavioral constellation similar to that seen in human type II alcoholism,
      for which considerable genetic loading has been shown. In search of novel neural
      substrates for this phenotype, we compared gene expression in the cerebral cortex
      of the AA rat with two groups of control animals, the ANA (alcohol non-accepting)
      line and heterogeneous Wistar animals, by differential display RT-PCR. We
      identified two transcripts, ribosomal protein L18a mRNA and diacyglycerol kinase
      iota mRNA, which are differentially expressed between AA and ANA rats. Ribosomal
      protein L18A mRNA is evenly expressed throughout the brain, but strongly reduced
      in cortex of AA rats vs controls. Diacylglycerol kinase iota is exclusively found
      in the brain, and expressed in a distinct regional pattern. Its cortical
      expression is about 25% higher in AA than ANA rats. Differential display RT-PCR
      seems to provide a feasible strategy to identify previously unknown genes whose
      differential expression correlates with behavioral phenotypes related to
      dependence.

PMID- 11244495
TI  - Association study of the low-activity allele of catechol-O-methyltransferase and
      alcoholism using a family-based approach.
AB  - Catechol-O-methyltransferase (COMT) is a major component of the metabolic
      pathways of neurotransmitters such as dopamine, adrenaline, and noradrenaline.
      The activity of COMT is known to vary within the population; it exists in common
      high- and low-activity forms that are determined by a Val --> Met polymorphism at
      amino acid position 108/158 (in soluble or membrane-bound COMT). Recently, the
      low-activity allele was reported to contribute to the development of late-onset
      alcoholism in men. The present study extends this study by utilizing a family
      based association approach, and by including individuals with early-onset
      alcoholism. Although no significant transmission disequilibrium was found in the
      overall sample of 70 parent/offspring trios (TDT = 1.43, P = 0.23), we observed a
      preferential transmission of the low-activity allele to patients with an early
      onset of disease (n = 32, TDT = 4.83, P = 0.028). Our results provide further
      evidence for an involvement of the COMT low-activity allele in the development of
      alcoholism and demonstrate the need for further studies in large samples of
      alcoholic patients.

PMID- 11244496
TI  - Progesterone modulation of D5 receptor expression in hypothalamic ANP neurons,
      the role of estrogen.
AB  - Aberrant responses to dopamine consequent to a reduction of D1-like receptors in
      critical regions of the brain have been implicated in schizophrenia. Whereas
      estrogen may protect against the onset and incidence of psychosis in the illness,
      the neurobiological effects of the ovarian steroid remain unclear. Recently we
      have shown that estrogen augments the expression of D5 receptors, a member of the
      D1-like receptor family, in central neurons and enhances the functions of the
      host cells. Employing rat hypothalamic neuron cultures, we report here that
      another important ovarian steroid, progesterone, also augments dopamine D5
      receptor expression in hypothalamic atrial natriuretic factor (ANP) neurons.
      However, unlike the effect of estrogen, progesterone acts indirectly through
      potentiating estrogen-mediated changes that include enhancement of D5 receptor
      expression, immunoreactive (ir)-ANP release and pro-ANP mRNA abundance. We
      conclude that whilst progesterone has little effect by itself, the steroid works
      in synergism with estrogen to augment the function of ANP neurons. The
      possibility that progesterone may further enhance the protective effect of
      estrogen against the incidence of psychosis in schizophrenia now needs to be
      considered.

PMID- 11244497
TI  - Disruption of protein phosphatase 2A subunit interaction in human cancers with
      mutations in the A alpha subunit gene.
AB  - The A subunit of protein phosphatase 2A (PP2A) consists of 15 nonidentical
      repeats. The catalytic C subunit binds to C-terminal repeats 11 - 15 and
      regulatory B subunits bind to N-terminal repeats 1 - 10. Recently, four cancer
      associated mutants of the A-alpha subunit have been described: Glu64-->Asp in
      lung carcinoma, Glu64-->Gly in breast carcinoma, Arg418-->Trp in melanoma, and
      Delta171 - 589 in breast carcinoma. Based on our model of PP2A, we predicted that
      Glu64-->Asp and Glu64-->Gly might be defective in B subunit binding, whereas
      Arg418-->Trp and Delta171 - 589 might bind neither B nor C subunits. We generated
      these mutants by site-directed mutagenesis and assayed their ability to associate
      with different forms of B subunits (B, B', B") or with the catalytic C subunit.
      The results demonstrate that all mutants are defective in binding either B or B
      and C subunits. Specifically, the N-terminal mutants, Glu64-->Asp and Glu64-
      >Gly, are defective in B' but normal in B, B", and C subunit binding, whereas the
      C-terminal mutants Arg418-->Trp and Delta171 - 589 bind none of the B subunits
      nor the C subunit. The implications of these findings with regard to the
      potential role of PP2A as a tumor suppressor are discussed. Oncogene (2001) 20,
      10 - 15.

PMID- 11244498
TI  - Activation of ErbB-2 via a hierarchical interaction between ErbB-2 and type I
      insulin-like growth factor receptor in mammary tumor cells.
AB  - The present study focused on interactions between signaling pathways activated by
      progestins and by type I and II receptor tyrosine kinases (RTKs) in mammary
      tumors. An experimental model in which the synthetic progestin
      medroxyprogesterone acetate (MPA) induced mammary adenocarcinomas in Balb/c mice
      was used. MPA-stimulated proliferation, both in vivo and in vitro, of progestin
      dependent tumors induced up-regulation of ErbB-2 protein levels and tyrosine
      phosphorylation of this receptor. Combinations of antisense oligodeoxynucleotides
      (ASODNs) directed to ErbB-2 mRNA with ASODNs directed to the insulin-like growth
      factor-I receptor (IGF-IR) were used to study the effect of the simultaneous
      block of these receptors on the MPA-induced proliferation of epithelial cells
      from the progestin-dependent C4HD line. Neither synergistic nor additive effects
      on the inhibition of MPA-induced proliferation of C4HD cells were observed as a
      result of the combination of these ASODNs. Suppression of IGF-IR expression by
      ASODNs resulted in complete abrogation of MPA-induced phosphorylation of ErbB-2
      in C4HD cells, whereas blockage of ErbB-2 did not affect IGF-IR phosphorylation.
      These results show the existence of a hierarchical interaction between IGF-IR and
      ErbB-2, by means of which IGF-IR directs ErbB-2 phosphorylation. We demonstrated,
      for the first time, that this hierarchical interaction involves physical
      association of both receptors, resulting in the formation of a heteromeric
      complex. Furthermore, confocal laser microscopy experiments demonstrated that MPA
      was able to induce co-localization of ErbB-2 and IGF-IR. This hetero-oligomer was
      also found in MCF-7 human breast cancer cells in which association of IGF-IR and
      ErbB-2 was induced by heregulin and IGF-I. Oncogene (2001) 20, 34 - 47.

PMID- 11244499
TI  - Overexpression of p97Eps8 leads to cellular transformation: implication of
      pleckstrin homology domain in p97Eps8-mediated ERK activation.
AB  - Two isoforms of Eps8, p97Eps8 and p68Eps8, have been identified as the substrates
      for receptor tyrosine kinases. Our previous studies indicated that both tyrosyl
      phosphorylation and protein expression of Eps8 were elevated in v-Src transformed
      cells. In an attempt to examine the role played by p97Eps8 in tumorigenesis, we
      have first obtained cells overexpressing p97Eps8 and its pleckstrin homology (PH)
      truncated variant. We then demonstrated that cells overexpressing p97Eps8 not
      only exhibited the ability of focus formation in cell culture but also promoted
      the tumor formation in mice as compared to controls. Furthermore, elevated serum
      induced extracellular responsive kinase (ERK) activation was observed in p97Eps8
      overexpressors. This enhanced ERK activation was sensitive to a MEK1 specific
      inhibitor PD98059 and was important for p97Eps8-mediated transformation, since
      transfection of vectors expressing dominant negative MEK1 and p97Eps8 abrogated
      focus formation by p97Eps8. In contrast, PH-truncated p97Eps8 failed to localize
      at the plasma membrane and that the truncated variant also did not elevate ERK
      activation and cellular transformation in response to serum stimulation. Our
      results thus indicated that: (i) the gene encoding p97Eps8 was an oncogene; (ii)
      p97Eps8-induced oncogenesis was partly mediated by ERK activation; and (iii) the
      PH domain of p97Eps8 was critical for its cellular localization, ERK activation
      and its ability to transform cells. Oncogene (2001) 20, 106 - 112.

PMID- 11244500
TI  - Regulation of Pax3 transcriptional activity by SUMO-1-modified PML.
AB  - Pax3 is an evolutionarily conserved transcription factor that plays a major role
      in a variety of developmental processes. Mutations in Pax3 lead to severe
      malformations as seen in human Waardenburg syndrome and in the Splotch mutant
      mice. The transcriptional activity of Pax3 was recently shown to be repressed by
      Daxx whereas the oncogenic fusion protein Pax3-FKHR is unresponsive to this
      repressive action. Here we demonstrate that Daxx-mediated repression of Pax3 can
      be inhibited by the nuclear body (NB)-associated protein PML. Interestingly, this
      suppression of Daxx properties correlates with its recruitment to the NBs.
      Factors such as arsenicals and interferons that enhance NB formation, trigger
      both the targeting of Daxx to these nuclear structures and the relief of the
      repressive activity of Daxx. Conversely, lack of structurally intact NBs
      profoundly impairs Pax3 transcriptional activity, likely by increasing the pool
      of available nucleoplasmic Daxx. Moreover, a PML mutant that can not be modified
      by the ubiquitin-related SUMO-1 modifier is no more able to interact with Daxx.
      Consistently, such a mutant fails both to inhibit the Daxx repressing effect on
      Pax3 and to induce its accumulation into the NBs. Taken together, these results
      argue that SUMO-1 modified PML can derepress Pax3 transcriptional activity
      through sequestration of the Daxx repressor into the NBs and suggest a role for
      these nuclear structures in the transcriptional control by Pax proteins. Oncogene
      (2001) 20, 1 - 9.

PMID- 11244501
TI  - Activated ras oncogene collaborates with HBx gene of hepatitis B virus to
      transform cells by suppressing HBx-mediated apoptosis.
AB  - The hepatitis B virus HBx protein is a promiscuous transactivator implicated in
      the development of hepatocellular carcinoma. The ectopic expression of HBx fails
      to transform both primary and immortalized rodent cells, but rather induces
      apoptosis. Furthermore, most transgenic mice harboring HBx do not develop liver
      tumors. Thus, it remains unclear whether and how HBx contributes to oncogenesis.
      Here, we show that HBx collaborates with activated H-ras to transform
      immortalized rodent cells. Indeed, REF52 cells transfected by both HBx and
      activated H-ras were morphologically transformed and were able to grow in soft
      agar. Remarkably, nude mice injected with REF52 cells transfected by both HBx and
      activated H-ras developed tumors, whereas the mice injected with REF52 cells
      transfected by either gene alone did not. Thus, we concluded that HBx could
      contribute to neoplastic transformation of cells in collaboration with other
      oncogenes, such as H-ras, that renders cells to overcome the HBx-mediated
      apoptosis. Further, we found that HBx mediated apoptosis was suppressed by
      activated H-ras through activation of the phosphatidylinositol-3 kinase and Akt
      pathway. Data presented here firmly established the oncogenic potential of HBx
      during multistage carcinogenesis. Oncogene (2001) 20, 16 - 23.

PMID- 11244502
TI  - Induction of epithelial differentiation and DNA demethylation in hamster
      malignant oral keratinocyte by ornithine decarboxylase antizyme.
AB  - The hamster ornithine decarboxylase antizyme (ODC-Az) cDNA was transfected into
      the hamster malignant oral keratinocyte cell line, HCPC-1. Ectopic expression of
      ODC-Az resulted in the reversion of malignant phenotypes and alteration of DNA
      methylation status of CCGG sites. The phenotypes examined include ODC enzymatic
      activity, doubling time, morphological change, anchorage dependent growth,
      tumorigenicity in nude mice, induction of epithelial differentiation marker
      protein (involucrin), and change of cell cycle position. Comparison of CCGG DNA
      methylation status of the ODC-Az and control vector transfectants revealed a
      significant increase in demethylation of 5-methyl cytosines (m5C) of CCGG sites
      in the ODC-Az transfectants. Ectopic expression of ODC-Az gene in hamster
      malignant oral keratinocytes led to reduce ODC activity and the subsequent
      demethylation of 5-methyl cytosines, presumably via the ODC/ polyamines/
      decarboxylated S-adenosylmethionine (dc-AdoMet) pathways. Our data suggest that
      ODC-Az shared the same pathway of polyamines/ dc-AdoMet/DNA methyltransferase
      (DNA MTase). We propose that ODC-Az mediates a novel mechanism in tumor
      suppression by DNA demethylation and presumably re-activation of key cellular
      genes silenced by DNA hypermethylation during cancer development. Oncogene (2001)
      20, 24 - 33.

PMID- 11244503
TI  - The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3
      transcription factor gene to ASPL, a novel gene at 17q25.
AB  - Alveolar soft part sarcoma (ASPS) is an unusual tumor with highly characteristic
      histopathology and ultrastructure, controversial histogenesis, and enigmatic
      clinical behavior. Recent cytogenetic studies have identified a recurrent der(17)
      due to a non-reciprocal t(X;17)(p11.2;q25) in this sarcoma. To define the
      interval containing the Xp11.2 break, we first performed FISH on ASPS cases using
      YAC probes for OATL1 (Xp11.23) and OATL2 (Xp11.21), and cosmid probes from the
      intervening genomic region. This localized the breakpoint to a 160 kb interval.
      The prime candidate within this previously fully sequenced region was TFE3, a
      transcription factor gene known to be fused to translocation partners on 1 and X
      in some papillary renal cell carcinomas. Southern blotting using a TFE3 genomic
      probe identified non-germline bands in several ASPS cases, consistent with
      rearrangement and possible fusion of TFE3 with a gene on 17q25. Amplification of
      the 5' portion of cDNAs containing the 3' portion of TFE3 in two different ASPS
      cases identified a novel sequence, designated ASPL, fused in-frame to TFE3 exon 4
      (type 1 fusion) or exon 3 (type 2 fusion). Reverse transcriptase PCR using a
      forward primer from ASPL and a TFE3 exon 4 reverse primer detected an ASPL-TFE3
      fusion transcript in all ASPS cases (12/12: 9 type 1, 3 type 2), establishing the
      utility of this assay in the diagnosis of ASPS. Using appropriate primers, the
      reciprocal fusion transcript, TFE3-ASPL, was detected in only one of 12 cases,
      consistent with the non-reciprocal nature of the translocation in most cases, and
      supporting ASPL-TFE3 as its oncogenically significant fusion product. ASPL maps
      to chromosome 17, is ubiquitously expressed, and matches numerous ESTs (Unigene
      cluster Hs.84128) but no named genes. The ASPL cDNA open reading frame encodes a
      predicted protein of 476 amino acids that contains within its carboxy-terminal
      portion of a UBX-like domain that shows significant similarity to predicted
      proteins of unknown function in several model organisms. The ASPL-TFE3 fusion
      replaces the N-terminal portion of TFE3 by the fused ASPL sequences, while
      retaining the TFE3 DNA-binding domain, implicating transcriptional deregulation
      in the pathogenesis of this tumor, consistent with the biology of several other
      translocation-associated sarcomas. Oncogene (2001) 20, 48 - 57.

PMID- 11244504
TI  - Suppression of the tumorigenicity of mutant p53-transformed rat embryo
      fibroblasts through expression of a newly cloned rat nonmuscle myosin heavy chain
      B.
AB  - In our previous study, a rat homolog of human nonmuscle myosin heavy chain-B
      (nmMHC-B) was identified by mRNA differential display comparing of transformed
      against nontransformed Rat 6 cells overexpressing mutant p53val135 gene. The
      nmMHC-B was found to be expressed in normal Rat 6 embryo fibroblast cell line,
      but markedly suppressed in the mutant p53val135-transformed Rat 6 cells. To
      examine the possible involvement of nmMHC-B in cell transformation, we first
      cloned and sequenced the full length cDNA of rat nmMHC-B, which was then cloned
      into an ecdysone-expression vector. The resulting construct was introduced into
      the T2 cell line, a mutant p53val135-transformed Rat 6 cells lacking the
      expression of the endogenous nmMHC-B. The clonal transfectants, expressing
      muristerone A-induced nmMHC-B, displayed a slightly flatter morphology and
      reached to a lower saturation density compared to the parental transformed cells.
      Reconstitution of actin filamental bundles was also clearly seen in cells
      overexpressing the nmMHC-B. In soft agar assays, nmMHC-B transfectants formed
      fewer and substantially smaller colonies than the parental cells in response to
      muristerone A induction. Moreover, it was strikingly effective in suppressing the
      tumorigenicity of the T2 cells when tested in nude mice. Thus, the nmMHC-B, known
      as a component of the cytoskeletal network, may act as a tumor suppressor gene.
      Our current finding may reveal a novel role of nmMHC-B in regulating cell growth
      and cell signaling in nonmuscle cells. Oncogene (2001) 20, 58 - 68.

PMID- 11244505
TI  - Expression of the NF-kappa B target gene IEX-1 (p22/PRG1) does not prevent cell
      death but instead triggers apoptosis in Hela cells.
AB  - P22PRG1/IEX-1 is a putative NF-kappaB target gene implicated in the regulation of
      cellular viability. Here, we show that in HeLa cells TNFalpha induces expression
      of p22PRG1/IEX-1 in an NF-kappaB dependent fashion. Blockade of NF-kappaB
      activation by various NF-kappaB inhibitors abolished TNFalpha-induced p22PRG1/IEX
      1 expression and increased the sensitivity to apoptosis induced by TNFalpha, an
      activating Fas-antibody or the anti-cancer drug etoposide. Surprisingly, ectopic
      expression of p22PRG1/IEX-1 in HeLa cells transfected with an inducible
      p22PRG1/IEX-1-expression vector augments the susceptibility to apoptosis
      initiated by death-receptor ligands or by etoposide. In addition, p22PRG1/IEX-1
      expressing HeLa cells exhibit an accelerated progression through the cell cycle.
      Transfection of an antisense hammerhead ribozyme targeted to p22PRG1/IEX-1
      reduced the speed in cell cycle progression and decreased the apoptotic response
      to death ligands. Our data demonstrate that p22PRG1/IEX-1 is specifically induced
      during NF-kappaB activation, but this seems not to be related to the anti
      apoptotic actions of NF-kappaB. Instead, NF-kappaB dependent recruitment of
      p22PRG1/IEX-1 might be related to a modulation in the cell cycle, and hereby,
      p22PRG1/IEX-1 may accelerate cell growth on the one hand, but may trigger
      apoptosis on the other. Oncogene (2001) 20, 69 - 76.

PMID- 11244506
TI  - Role of direct interaction in BRCA1 inhibition of estrogen receptor activity.
AB  - The BRCA1 gene was previously found to inhibit the transcriptional activity of
      the estrogen receptor [ER-alpha] in human breast and prostate cancer cell lines.
      In this study, we found that breast cancer-associated mutations of BRCA1 abolish
      or reduce its ability to inhibit ER-alpha activity and that domains within the
      amino- and carboxyl-termini of the BRCA1 protein are required for the inhibition.
      BRCA1 inhibition of ER-alpha activity was demonstrated under conditions in which
      a BRCA1 transgene was transiently or stably over-expressed in cell lines with
      endogenous wild-type BRCA1 and in a breast cancer cell line that lacks endogenous
      functional BRCA1 (HCC1937). In addition, BRCA1 blocked the expression of two
      endogenous estrogen-regulated gene products in human breast cancer cells: pS2 and
      cathepsin D. The BRCA1 protein was found to associate with ER-alpha in vivo and
      to bind to ER-alpha in vitro, by an estrogen-independent interaction that mapped
      to the amino-terminal region of BRCA1 (ca. amino acid 1-300) and the conserved
      carboxyl-terminal activation function [AF-2] domain of ER-alpha. Furthermore,
      several truncated BRCA1 proteins containing the amino-terminal ER-alpha binding
      region blocked the ability of the full-length BRCA1 protein to inhibit ER-alpha
      activity. Our findings suggest that the amino-terminus of BRCA1 interacts with ER
      alpha, while the carboxyl-terminus of BRCA1 may function as a transcriptional
      repression domain. Oncogene (2001) 20, 77 - 87.

PMID- 11244507
TI  - Mutations of the Smad4 gene in acute myelogeneous leukemia and their functional
      implications in leukemogenesis.
AB  - The Smad family proteins are critical components of the transforming growth
      factor (TGF)-beta signaling pathway. TGF-beta is a multipotent cytokine that
      elicits many biological functions. In particular, TGF-beta exhibits effects on
      the cell cycle manifested by G1-phase arrest, differentiation, or apoptosis of
      several target cells, suggesting that disruption of TGF-beta signaling pathway
      could be involved in cancer formation. Here we show one missense mutation of the
      Smad4 gene in the MH1 domain (P102L) and one frame shift mutation resulting in
      termination in the MH2 domain (Delta(483 - 552)) in acute myelogeneous leukemia.
      Both of the mutated Smad4 proteins lack transcriptional activities. Concomitant
      expression of the P102L mutant with wild-type Smad4 inactivates wild-type Smad4
      through inhibiting its DNA-binding ability. The Delta(483 - 552) mutant blocks
      nuclear translocation of wild-type Smad4 and thus disrupts TGF-beta signaling.
      This is the first report showing that mutations in the Smad4 gene are associated
      with the pathogenesis of acute myelogeneous leukemia and the obtained results
      should provide useful insights into the mechanism whereby disruption of TGF-beta
      signaling pathway could lead to acute myelogeneous leukemia. Oncogene (2001) 20,
      88 - 96.

PMID- 11244508
TI  - The angiogenic factor midkine is aberrantly expressed in NF1-deficient Schwann
      cells and is a mitogen for neurofibroma-derived cells.
AB  - Loss of the tumor suppressor gene NF1 in neurofibromatosis type 1 (NF1)
      contributes to the development of a variety of tumors, including malignant
      peripheral nerve sheath tumors (MPNST) and benign neurofibromas. Of the different
      cell types found in neurofibromas, Schwann cells usually provide between 40 and
      80%, and are thought to be critical for tumor growth. Here we describe the
      identification of growth factors that are upregulated in NF1-/- mouse Schwann
      cells and are potential regulators of angiogenesis and cell growth. Basic
      fibroblast growth factor (FGF-2), platelet-derived growth factor (PDGF) and
      midkine (MK) were found to be induced by loss of neurofibromin and MK was further
      characterized. MK was induced in human neurofibromas, schwannomas, and various
      nervous system tumors associated with NF1 or NF2; midkine showed an expression
      pattern overlapping but distinct from its homolog pleiotrophin (PTN).
      Immunohistochemistry revealed expression of MK in S-100 positive Schwann cells of
      dermal and plexiform neurofibromas, and in endothelial cells of tumor blood
      vessels, but not in normal blood vessels. Furthermore, MK demonstrated potent
      mitogenic activity for human systemic and brain endothelial cells in vitro and
      stimulated proliferation and soft agar colony formation of human MPNST derived
      S100 positive cells and fibroblastoid cells derived from an NF1 neurofibroma. The
      data support a possible central role for MK as a mediator of angiogenesis and
      neurofibroma growth in NF1. Oncogene (2001) 20, 97 - 105.

PMID- 11244509
TI  - Increased p53 phosphorylation after microtubule disruption is mediated in a
      microtubule inhibitor- and cell-specific manner.
AB  - p53 is present at low levels in unstressed cells. Numerous cellular insults,
      including DNA damage and microtubule disruption, elevate p53 protein levels.
      Phosphorylation of p53 is proposed to be important for p53 stabilization and
      activation after genotoxic stress; however, p53 phosphorylation after microtubule
      disruption has not been analysed. The goal of the current study was to determine
      if p53 phosphorylation increases after microtubule disruption, and if so, to
      identify specific p53 residues necessary for microtubule inhibitor-induced
      phosphorylation. Two dimensional gel analyses demonstrated that the number of p53
      phospho-forms in cells increased after treatment with microtubule inhibitors
      (MTIs) and that the pattern of p53 phosphorylation was distinct from that
      observed after DNA damage. p53 phosphorylation also varied in a MTI-dependent
      manner, as Taxol and Vincristine induced more p53 phospho-forms than nocodazole.
      Further, MTI treatment increased phosphorylation of p53 on serine-15 in
      epithelial tumor cells. In contrast, serine-15 phosphorylation of p53 did not
      increase in MTI-treated primary cultures of human fibroblasts. Analysis of
      ectopically expressed p53 phospho-mutant proteins from Taxol- and nocodazole
      treated cells indicated that multiple p53 amino terminal residues, including
      serine-15 and threonine-18, were required for Taxol-mediated phosphorylation of
      p53. Taken together, the results of this study demonstrate that distinct p53
      phospho-forms are induced by MTI treatment as compared to DNA damage and that p53
      phosphorylation is mediated in a MTI- and cell-specific manner. Oncogene (2001)
      20, 113 - 124.

PMID- 11244510
TI  - BS69, an adenovirus E1A-associated protein, inhibits the transcriptional activity
      of c-Myb.
AB  - The carboxyl terminus of c-Myb contains a negative regulatory domain that is
      absent in the v-Myb oncoprotein, but conserved among all the known Myb proteins
      of animals. This domain inhibits transcriptional activation by c-Myb in animal
      cells, but not in budding yeast, suggesting that additional protein(s) present in
      animal cells but not yeast are required for this negative regulatory function. A
      yeast two-hybrid screen identified BS69, an adenovirus E1A-associated protein, as
      interacting with the carboxy-terminal region of c-Myb. BS69 contains regions of
      similarity to the PHD finger, the bromodomain, and the MYND domain, all of which
      are found in other proteins present in high molecular weight complexes that
      regulate transcription and/or modify chromatin structure. Further study showed
      that BS69 inhibited the transcriptional activity of c-Myb, that this inhibition
      was specific, that it mapped to the carboxyl termini of the two proteins and that
      it was dose-dependent. A direct interaction between these two proteins was
      observed in vitro. Furthermore, the 289R E1A protein could inhibit the BS69
      mediated decrease in transcriptional activation by c-Myb. By analogy with the
      inhibition of the Rb/E2F regulatory axis by E1A, we propose that a BS69/Myb
      regulatory circuit may also be a target of disruption during oncogenesis.
      Oncogene (2001) 20, 125 - 132.

PMID- 11244513
TI  - Historical background and lessons learned from early randomized trials.

PMID- 11244511
TI  - Inhibition of integrin linked kinase (ILK) suppresses beta-catenin-Lef/Tcf
      dependent transcription and expression of the E-cadherin repressor, snail, in APC
      /- human colon carcinoma cells.
AB  - Loss of functional adenomatous polyposis coli (APC) protein results in the
      stabilization of cytosolic beta-catenin and activation of genes that are
      responsive to Lef/Tcf family transcription factors. We have recently shown that
      an independent cell adhesion and integrin linked kinase (ILK)-dependent pathway
      can also activate beta-catenin/LEF mediated gene transcription and downregulate E
      cadherin expression. In addition, ILK activity and expression are elevated in
      adenomatous polyposis and colon carcinomas. To examine the role of this pathway
      in the background of APC mutations we inhibited ILK activity in APC-/- human
      colon carcinoma cell lines. In all cases, inhibition of ILK resulted in
      substantial inhibition of TCF mediated gene transcription and inhibition of
      transcription and expression of the TCF regulated gene, cyclin D1. Inhibition of
      ILK resulted in decreased nuclear beta-catenin expression, and in the inhibition
      of phosphorylation of GSK-3 and stimulation of its activity, leading to
      accelerated degradation of beta-catenin. In addition, inhibition of ILK
      suppressed cell growth in culture as well as growth of human colon carcinoma
      cells in SCID mice. Strikingly, inhibition of ILK also resulted in the
      transcriptional stimulation of E-cadherin expression and correlated with the
      inhibition of gene transcription of snail, a repressor of E-cadherin gene
      expression. Overexpression of ILK caused a stimulation of expression of snail,
      but snail expression was found not to be regulated by beta-catenin/Tcf. These
      data demonstrate that ILK can regulate beta-catenin/TCF and snail transcription
      factors by distinct pathways. We propose that inhibition of ILK may be a useful
      strategy in the control of progression of colon as well as other carcinomas.
      Oncogene (2001) 20, 133 - 140.

PMID- 11244514
TI  - Morphological analysis of atherosclerotic plaque retrieved by coronary
      atherectomy.
AB  - The development of atherectomy catheters and their use in clinical practice
      during percutaneous revascularization procedures permitted the analysis of the
      pathophysiology of obstructive coronary disease in vivo. The various clinical
      presentations of coronary disease are related to distinct morphological aspects
      of the culprit coronary stenosis as assessed by angiography, angioscopy or
      intravascular ultrasound imaging. Analysis of plaque fragments revealed the
      underlying histopathology. Restenotic lesions following various mechanical
      interventions have been studied in detail both in native coronary arteries and in
      bypass conduits. The biological reaction to implantation of endovascular stents
      involves inflammation around the stent wires as well as smooth muscle cell
      proliferation. Specific processes such as nitric oxide production or the activity
      of intramural proteases can be characterized and contribute to identify targets
      for future pharmacological therapy.

PMID- 11244515
TI  - Further insights into coronary debulking: the EUROCARE trial of directional
      atherectomy and the PACT trial of pullback atherectomy.
AB  - Although the principle of reducing plaque load in the coronary artery remains
      very appealing, clinical benefit from debulking devices has not been demonstrated
      unequivocally. Other approaches to prevent restenosis had been the application of
      various pharmacological agents. Unfortunately, the majority of clinical studies
      have not reproduced the promising results observed in the experimental
      laboratories. New frontiers in improving atherectomy devices and in optimizing
      concomitant medical treatment are currently being explored. We report on the
      EUROCARE trial investigating the possible benefit of carvedilol after coronary
      atherectomy, and the Pullback Atherectomy (PAC) pilot trial using a novel
      atherectomy device.

PMID- 11244516
TI  - Directional coronary atherectomy: optimal atherectomy trials and new combined
      strategies with coronary stents.
AB  - Directional coronary atherectomy (DCA) has evolved from its early use as a tool
      for minimal plaque debulking to its current use of more aggressive lumen
      enlargement. The trend toward improved lumen results and reduced restenosis
      following DCA compared to percutaneous transluminal coronary angioplasty (PTCA)
      in the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT) was
      confirmed as a significant improvement in the subsequent Balloon versus Optimal
      Atherectomy Trial (BOAT). BOAT showed that acute lumen results and late
      angiographic restenosis could be significantly improved by DCA over PTCA, without
      any increase in procedural complications or late cardiac events. The role of DCA
      in conjunction with coronary stents is currently being defined as studies suggest
      that residual plaque burden after stenting is predictive of late restenosis. The
      Atherectomy before Multilink Stent Improves Lumen Gain and Clinical Outcomes
      Study (AMIGO) will help determine whether plaque debulking prior to stenting can
      reduce restenosis.

PMID- 11244517
TI  - The place of rotablator for treatment of in-stent restenosis.
AB  - In-stent restenosis (ISR) is still a growing problem in interventional cardiology
      due to the increasing number of stent implantations. Various treatment modalities
      are available at present. As a non ablative strategy balloon angioplasty is the
      strategy of choice for focal ISR, while ablative techniques such as directional
      coronary atherectomy, Excimer laser coronary angioplasty and rotational
      atherectomy are used preferentially in diffuse restenosis processes. These
      debulking techniques are optimized by peri-interventional use of intravascular
      ultrasound and adjunctive balloon angioplasty. Study data comparing different
      interventional approaches, usually with adjunct balloon angioplasty, have not
      proven an optimal treatment modality for ISR yet.

PMID- 11244518
TI  - The place of directional coronary atherectomy for the treatment of in-stent
      restenosis.
AB  - The beneficial short and long-term results of coronary stenting have resulted in
      a dramatic increase in stent utilization, accounting for greater than 80% of
      coronary interventions [1--9]. However, the long-term beneficial effect of
      coronary stenting is limited by the occurrence of a 14 to 61% restenosis rate [10
      -13]. The optimal percutaneous revascularization strategy for the treatment of in
      stent restenosis remains undetermined. Although balloon angioplasty has been
      performed with high initial procedural success, the long-term results are
      disappointing due to significant recurrence [14--18]. In this article we describe
      the feasibility, safety, immediate and long-term outcome of directional coronary
      atherectomy (DCA) as a treatment modality in a cohort of patients undergoing
      percutaneous intervention for the treatment of in-stent restenosis at the
      Massachusetts General Hospital.

PMID- 11244519
TI  - Atherectomy plus stenting: what do we gain?
AB  - Coronary stents have improved the short and long-term outcomes of selected
      patients undergoing catheter-based coronary interventions. However, the use of
      these devices in complex coronary lesions has also created an incessant form of
      in-stent restenosis that still defies treatment. Plaque burden has been
      recognized as an important factor that may incite neo-intimal proliferation after
      stent implantation. Prospective non-randomized experience has shown that plaque
      removal prior to stent implantation using directional atherectomy is a promising
      approach to reduce restenosis in selected patients. However, the proof of concept
      awaits the results of the randomized trials. Ultimately, the clinical utility of
      this approach will depend upon: (1) further improvements on the current
      directional atherectomy device; (2) minimizing the incidence of non-Q-wave
      myocardial infarction with selective use of IIb-IIIa platelet receptor
      antagonists or distal protection devices; (3) targeting patients at high risk for
      restenosis in whom efficient debulking is feasible such as non-calcified lesions
      in vessels >2.75 mm and <3.5 mm in diameter that require long stents, aorto
      ostial lesions, bifurcational lesions, and chronic total occlusions.

PMID- 11244520
TI  - Presbyacusis.

PMID- 11244521
TI  - Otology in ancient India.
AB  - Sushrutra Samhita is essentially a multi-volume textbook reporting the surgical
      practices of ancient India. It covers all aspects of surgery. However, specific
      references are made to otorhinological conditions, their description and
      subsequent treatments often being described in some detail. In this paper we
      outline the structure of the document and attempt to explain its underlying
      philosophies. We highlight the specific references to otological diseases and
      their treatment and draw the obvious comparisons with modern otological practice.

PMID- 11244522
TI  - Value of investigation in the diagnosis of allergic fungal rhinosinusitis:
      results of a prospective study.
AB  - The authors report a prospective study in which the aim was to analyse the
      usefulness of different criteria in optimizing the diagnosis of allergic fungal
      rhinosinusitis. From 1995 to 1998, 165 patients were operated on for chronic
      rhinosinusitis. Investigations used in this study for the diagnosis of allergic
      Aspergillus rhinosinusitis consisted of an analysis of clinical, radiological,
      immuno-allergic criteria. Fourteen patients presented with allergic Aspergillus
      rhinosinusitis. One hundred and fifty-one patients did not present any of the
      necessary criteria for the diagnosis of allergic Aspergillus rhinosinusitis. The
      results show that the characteristic macroscopic appearance, the maxillary sinus
      localization, and the presence of positive specific IgE to Aspergillus fumigatus
      are arguments that reinforce the diagnostic certitude of allergic fungal
      sinusitis. No specific clinical or radiological criteria orients a diagnosis of
      chronic rhinosinusitis toward that of allergic fungal rhinosinusitis. The other
      immuno-allergic tests do not contribute to the diagnosis of allergic fungal
      rhinosinusitis. pathological, mycological, and

PMID- 11244524
TI  - Surgical management of septal perforation: an alternative to closure of
      perforation.
AB  - The surgical closure of septal perforations remains a distinctive challenge to
      the otorhinolaryngologist. This is demonstrated by the modest success in most
      techniques. An alternative method, involving surgical enlargement of the
      perforation with posterior edge repair, is described and the outcome is
      investigated. Thirteen patients with perforations of up to 50 mm in size
      underwent this technique. A questionnaire interview was conducted and symptom
      scores were obtained. The length of hospitalization, follow-up period and post
      operative complications were evaluated as were measures of morbidity. The results
      showed a significant improvement in the symptom scores for nasal crusting,
      epistaxis and overall discomfort. This technique is straightforward and is
      especially suitable for larger perforations. The successful improvement in
      symptoms and an associated low morbidity makes it a complement to alternative
      surgical closure techniques.

PMID- 11244523
TI  - Endoscopic carbon dioxide laser turbinoplasty.
AB  - In the present work we describe the management of hypertrophied inferior
      turbinates using CO(2) laser in the UniPulse mode. The laser beam is delivered
      through the nasal probe delivery system, and the procedure is performed using the
      0 degrees endoscope. The UniPulse mode allowed fine-tuned, char-free tissue
      ablation, and the nasal probes allowed delivery of laser energy to the posterior
      parts of the inferior turbinates. The procedure was performed on 149 patients.
      The one-year post-operative follow-up period revealed good functional results in
      131 patients (88 per cent). The minimal nasal cross sectional area increased
      significantly from 0.52 cm(2) to 0.81 cm(2). The average decongestive effect, on
      the other hand, decreased from 0.26 cm(2) to 0.07 cm(2) indicating significant
      laser-induced fibrosis. The operation can be performed as an out-patient
      procedure with little or no morbidity.

PMID- 11244525
TI  - Ectopic adenoid tissue in the choanae.
AB  - A series of 19 patients with often long-lasting nasal stenosis despite repeated
      treatment attempts, including in many cases repeated adenoidectomy, were found to
      have ectopic adenoid tissue in the choanae which could only be removed
      transnasally by forceps. It did not emerge from the rhinopharynx but from the
      roof of the choanae, the posterior part of the nasal septum and in some cases
      also from the lateral wall of the choanae. The diagnosis was established by
      anterior rhinoscopy using a flexible rhinopharyngo-laryngoscope. The treatment
      was successful in all 19 patients, many of whom had had symptoms for years. It is
      estimated that about two per cent of patients with adenoid symptoms have such
      ectopic choanal adenoid tissue, that cannot be removed by the usual oral
      approach. In young patients with long-lasting nasal stenosis attention should be
      focused on the bottleneck of the nasopharyngeal airway formed by the choanae,
      primarily by fibre-optic endoscopic examination.

PMID- 11244526
TI  - Stomal recurrence following temporary tracheostomy.
AB  - The development of a stomal recurrence after temporary tracheostomy for malignant
      disease of the head and neck is a rare complication, but is a well-recognized
      phenomenon following total laryngectomy. The risk factors and mechanisms involved
      are still not well understood. In a review of 265 patients having a temporary
      tracheostomy for head and neck malignancy, three (one per cent) developed a
      stomal recurrence. All recurrences occurred in the group where tracheostomy had
      been performed pre-resection and of these three patients all had N+ disease. The
      findings suggest that tumour-cell implantation is an important mechanism of
      stomal recurrence and that operative technique and timing of tracheostomy
      placement is important in reducing the risk of encountering this complication.

PMID- 11244527
TI  - Audit of pain management at home following tonsillectomy in children.
AB  - The pain experienced at home and the burden this places on primary care resources
      is considerable following tonsillectomy in children. This was audited by postal
      questionnaire in 52 patients (36 responders). We found a significant proportion
      of patients experiencing moderately severe to severe pain and a high rate of
      consultation with general practitioners (50 per cent) for pain-related issues.
      These findings lead to changes in practice which included the provision of five
      days discharge medication (paracetamol/ibuprofen in non-asthmatics;
      paracetamol/dihydrocodeine in asthmatics) and improved written discharge advice.
      On re-auditing a year later in 100 patients (56 responders), we found reduced
      rates of consultation with general practitioners (27 per cent). However, the
      proportion of children experiencing moderately severe to severe pain was not
      reduced probably because most children were given the recommended analgesia
      during the first audit. We also found that paracetamol and ibuprofen was superior
      to paracetamol and dihydrocodeine for analgesia (p <0.05). Suggestions for
      further improvements are discussed.

PMID- 11244528
TI  - Self-made tooth guard using Turbocast.
AB  - Tooth protection during suspension microlaryngeal surgery is a challenge when
      teeth are damaged or missing. We present an effective, disposable and cheap tooth
      guard for microlaryngeal surgical procedures using Turbocast. The tooth guard
      transits the laryngoscope's pressure directly to the hard palate leaving the
      teeth uninvolved and free of any pressure.

PMID- 11244529
TI  - The fish hook retractor.
AB  - We describe a simple and easily adjustable method of retracting skin flaps during
      head and neck surgery. It involves the use of a modified fish hook and rubber
      band. The retractor is easily applied and adjusted, and inexpensive to
      manufacture.

PMID- 11244530
TI  - Cholesteatoma causing facial nerve transection.
AB  - Cholesteatoma is a well recognized cause of a facial nerve palsy. The usual
      mechanism for this complication is direct pressure on the nerve. We present a
      case in which the facial nerve has been transected by cholesteatoma and discuss
      the possible causes.

PMID- 11244531
TI  - Adenoma in the middle ear: a report of two cases.
AB  - Middle-ear adenoma has been reported only in small numbers by surgeons. The few
      large series reported have been presented by histopathologists. We add two cases
      of middle-ear adenoma to the published literature, together with pre-, per- and
      post-operative imaging of one case, as a demonstration of this rare clinical
      entity. We discuss the pathology of middle-ear adenoma, its diagnosis and
      treatment, and suggest ways of improving its management.

PMID- 11244532
TI  - A case of rhinoscleroma treated with ciprofloxacin.
AB  - Respiratory scleroma (often termed 'rhinoscleroma') is a chronic inflammatory
      condition in which deforming masses of tissue distend the nasal cavity.
      Klebsiella rhinoscleromatis is the causative agent of this infection and the
      Mikulicz cell is specific to the lesion being a large macrophage with clear
      cytoplasm containing the bacilli. Antibiotic therapy has traditionally consisted
      of streptomycin and tetracycline long-term but this presents problems with
      adverse side-effects and poor patient compliance. We report on a young patient
      with nasal rhinoscleroma who achieved resolution after treatment with oral
      ciprofloxacin. As mentioned in a review of patients with rhinoscleroma at the
      Mayo clinic in 1993, the fluoroquinolones deserve further study as potentially
      highly effective agents for this condition. Ciprofloxacin is convenient for oral
      administration and has few adverse effects. It achieves good tissue penetration,
      is concentrated in macrophages and may prove to be useful in the therapy of
      rhinoscleroma.

PMID- 11244533
TI  - Eosinophilic angiocentric fibrosis affecting the nasal cavity. A mucosal variant
      of the skin lesion granuloma faciale.
AB  - Eosinophilic angiocentric fibrosis (EAF) is an unusual fibrotic condition
      affecting the mucosa of the upper respiratory tract, of which there have been
      eight reported cases. The condition is thought to be associated with the rare
      skin disorder granuloma faciale, which is histologically identical, and was
      present in two cases of EAF. We report the third case where EAF and granuloma
      faciale occurred together, to highlight this type of intranasal fibrosis as a
      distinct pathological entity.

PMID- 11244534
TI  - Isolated inverted papilloma of the sphenoid sinus.
AB  - Inverted papilloma is a rare benign sinonasal tumour, characterized by a
      potentially invasive nature. The lateral nasal wall represents the most common
      site of origin, whereas paranasal sinuses are quite frequently found to be
      involved by extension. In contrast, primary sinus inverted papillomas have rarely
      been reported. The present study describes an extremely rare case of inverted
      papilloma, isolated to the left sphenoid sinus, that was treated by a transnasal
      endoscopic procedure. The therapeutic approach chosen is discussed and the
      results of a two-year follow-up are also presented.

PMID- 11244535
TI  - Laryngeal myxoma.
AB  - Myxoma is an uncommon neoplasm in the head and neck region. Laryngeal myxomas are
      rarer still. We report a case of a large myxoma in the supraglottis, that was
      excised endoscopically.

PMID- 11244536
TI  - Serious complication of tongue piercing.
AB  - The case of an 18-year-old patient who developed critical upper airway compromise
      after central tongue piercing is presented. Otolaryngologists must be aware of
      the many potential complications of tongue piercing and their management.

PMID- 11244537
TI  - Tuberculous parotitis: a series of five cases diagnosed on fine needle aspiration
      cytology.
AB  - Parotid gland tuberculosis is still a rare entity and has mostly been diagnosed
      after parotidectomy. We present five cases which were diagnosed on fine needle
      aspiration cytology (FNAC) and managed medically avoiding surgical intervention.

PMID- 11244538
TI  - Jugular thrombosis following tonsillectomy.
AB  - An unusual case of internal jugular thrombosis following routine tonsillectomy is
      presented. Guidelines for the clinical management of this case, with
      anticoagulants, do not exist.

PMID- 11244539
TI  - Differential diagnosis of a lateral cervical cyst and solitary cystic lymph node
      metastasis of occult thyroid papillary carcinoma.
AB  - We present a case of solitary cystic lymph node metastasis from an occult thyroid
      papillary carcinoma mimicking a lateral cervical cyst, and a case of thyroid
      papillary carcinoma with a true lateral cervical cyst. Based on a comparison of
      the radiographical findings of the two cases, differential diagnosis between
      cystic lymph node metastasis of papillary carcinoma and branchial cyst is
      discussed.

PMID- 11244540
TI  - Neural hearing loss in a child with poliomyelitis: a histopathological study.
AB  - The temporal bones of a 26-month-old white female with a paralytic syndrome
      clinically and pathologically identical to poliomyelitis were examined. The
      aetiological agent was unknown although a non-poliomyelitis enterovirus infection
      seemed likely. There was a complete absence of the cochlear neurons and
      substantially reduced peripheral and central axons with loss of some inner hair
      cells but preservation of outer hair cells. Scarpa's ganglion, and the geniculate
      ganglion were partially atrophied. The saccule and utricle were mildly dilated
      and Reissner's membrane of the apical turn was bulging. In two previous
      audiological studies a 10--20 dB bilateral sensorineural hearing loss was found
      in poliomyelitis patients and a neuronal lesion was postulated which is now
      supported by our findings. This is a rare example of an almost pure neural
      hearing loss.

PMID- 11244541
TI  - Intra-parenchymal thyroid epidermal cyst presenting with a left recurrent
      laryngeal nerve palsy.
AB  - We present a rare case of an intra-parenchymal thyroid epidermal cyst presenting
      with a left recurrent laryngeal nerve palsy. There was a complete recovery of the
      nerve function following surgical excision of the lesion. Theories of aetio
      pathogenesis of the cyst and underlying mechanisms responsible for the nerve
      paralysis are explored.

PMID- 11244542
TI  - Self-organizing dynamics of lexical access in normals and aphasics.
AB  - The goal of this article is to illustrate the application of self-organizing
      dynamics in the design of a model of lexical access. We focus particularly on the
      mapping of sound structure on to the lexicon and the influence of that structure
      on lexical access. The approach is tested in a series of two sets of simulations
      that explicate how lexical access might occur in normal subjects and aphasic
      patients. Both sets of simulations address the behavioral effects of both
      phonological and phonetic variability of prime stimuli on the magnitude of
      semantic priming. Results show that the model can successfully account for the
      behavioral effects associated with several kinds of acoustic manipulation,
      competitor presence, and the unfolding of those effects over time--primarily
      because it balances three important control parameters: resting lexical
      activation, positive feedback, and negative feedback. These simulations are
      offered as support (in the form of an existence proof) that deficits in the
      degree of lexical activation can account for the lexical processing impairments
      shown by Broca's aphasics who have reduced lexical activation, and Wernicke's
      aphasics who have increased lexical activation. Overall, results suggest that the
      present approach promises to offer a coherent theoretical framework within which
      to link empirical evidence in language processing and cognitive neuroscience in
      terms of possible underlying mechanisms.

PMID- 11244543
TI  - A limit to the speed of processing in ultra-rapid visual categorization of novel
      natural scenes.
AB  - The processing required to decide whether a briefly flashed natural scene
      contains an animal can be achieved in 150 msec (Thorpe, Fize, & Marlot, 1996).
      Here we report that extensive training with a subset of photographs over a 3-week
      period failed to increase the speed of the processing underlying such Rapid
      Visual Categorizations: Completely novel scenes could be categorized just as fast
      as highly familiar ones. Such data imply that the visual system processes new
      stimuli at a speed and with a number of stages that cannot be compressed. This
      rapid processing mode was seen with a wide range of visual complex images,
      challenging the idea that short reaction times can only be seen with simple
      visual stimuli and implying that highly automatic feed-forward mechanisms
      underlie a far greater proportion of the sophisticated image analysis needed for
      everyday vision than is generally assumed.

PMID- 11244544
TI  - Binding personal and peripersonal space: evidence from tactile extinction.
AB  - Behavioral and neurophysiological studies suggest that the brain constructs
      different representations of space. Among these representations are personal and
      peripersonal space. Personal space refers to the space occupied by our bodies.
      Peripersonal space refers to the space surrounding our bodies, which can be
      reached by our limbs. How these two representations are bound to give a unified
      sense of space in which humans act is not clear. We tested 10 patients with
      tactile extinction to investigate this issue. Tactile extinction is an
      attentional disorder in which patients are unaware of being touched on their
      contralesional limb if they are also touched simultaneously on their ipsilesional
      limb. We hypothesized that mechanisms that bind personal and peripersonal
      representations would improve these patients' awareness of being touched on their
      contralesional limbs. Visual--tactile integration and intentional movements were
      considered candidate mechanisms. Patients were more likely to be aware of
      contralesional touch when looking towards their contralesional limb than when
      looking towards their ipsilesional limb, and when actively moving on tactile
      probes than when receiving tactile stimuli passively. The improved awareness of
      being touched on the contralesional limb under these conditions suggests that
      cross-sensory and sensorimotor integration help bind personal and peripersonal
      space.

PMID- 11244545
TI  - Encoding of categories by noncategory-specific neurons in the inferior temporal
      cortex.
AB  - In order to understand how the brain codes natural categories, e.g., trees and
      fish, recordings were made in the anterior part of the macaque inferior temporal
      (IT) cortex while the animal was performing a tree/nontree categorization task.
      Most single cells responded to exemplars of more than one category while other
      neurons responded only to a restricted set of exemplars of a given category.
      Since it is still not known which type of cells contribute and what is the nature
      of the code used for categorization in IT, we have performed an analysis on
      single-cell data. A Kohonen self-organizing map (SOM), which uses an unsupervised
      (competitive) learning algorithm, was used to study the single cell responses to
      tree and nontree images. Results from the Kohonen SOM indicated that the
      collected neuronal data consisting of spike counts was sufficient to account for
      a good level of categorization success (approximately 83%) when categorizing a
      group of 200 trees and nontrees. Contrary to intuition, the results of the
      investigation suggest that the population of category-specific neurons (neurons
      that respond only to trees or only to nontrees) was unimportant to the
      categorization. Instead, a large majority of the neurons that were most important
      to the categorization was found to belong to a class of more broadly tuned cells,
      namely, cells that responded to both categories but that favored one category
      over the other by seven or more images. A simple algebraic operation (without the
      Kohonen SOM) between the above-mentioned noncategory-specific neurons confirmed
      the contribution of these neurons to categorization. Thus, the modeling results
      suggest (1) that broadly tuned neurons are critical for categorization, and (2)
      that only one additional layer of processing is required to extract the
      categories from a population of IT neurons.

PMID- 11244546
TI  - Brain potentials reflect behavioral differences in true and false recognition.
AB  - People often falsely recognize nonstudied lures that are semantically similar to
      previously studied words. Behavioral research suggests that such false
      recognition is based on high semantic overlap between studied items and lures
      that yield a feeling of familiarity, whereas true recognition is more often
      associated with the recollection of details. Despite this behavioral evidence for
      differences between true and false recognition, research measuring brain activity
      (PET, fMRI, ERP) has not clearly differentiated corresponding differences in
      brain activity. A median split was used to separate subjects into Good and Poor
      performers based on their discrimination of studied targets from similar lures.
      Only Good performers showed late (1000--1500 msec), right frontal event-related
      brain potentials (ERPs) that were more positive for targets and lures compared
      with new items. The right frontal differences are interpreted as reflecting
      postretrieval evaluation processes that were more likely to be engaged by Good
      than Poor performers. Both Good and Poor performers showed a parietal ERP old/new
      effect (400--800 msec), but only Poor performers showed a parietal old/lure
      difference. These results are consistent with the view that the parietal and
      frontal ERP old/new effects reflect dissociable processes related to
      recollection.

PMID- 11244547
TI  - Motor learning of compatible and incompatible visuomotor maps.
AB  - Brain imaging studies demonstrate increasing activity in limb motor areas during
      early motor skill learning, consistent with functional reorganization occurring
      at the motor output level. Nevertheless, behavioral studies reveal that visually
      guided skills can also be learned with respect to target location or possibly eye
      movements. The current experiments examined motor learning under compatible and
      incompatible perceptual/motor conditions to identify brain areas involved in
      different perceptual-motor transformations. Subjects tracked a continuously
      moving target with a joystick-controlled cursor. The target moved in a repeating
      sequence embedded within random movements to block sequence awareness.
      Psychophysical studies of behavioral transfer from incompatible (joystick and
      cursor moving in opposite directions) to compatible tracking established that
      incompatible learning was occurring with respect to target location. Positron
      emission tomography (PET) functional imaging of compatible learning identified
      increasing activity throughout the precentral gyrus, maximal in the arm area.
      Incompatible learning also led to increasing activity in the precentral gyrus,
      maximal in the putative frontal eye fields. When the incompatible task was
      switched to a compatible response and the previously learned sequence was
      reintroduced, there was an increase in arm motor cortex. The results show that
      learning-related increases of brain activity are dynamic, with recruitment of
      multiple motor output areas, contingent on task demands. Visually guided motor
      sequences can be linked to either oculomotor or arm motor areas. Rather than
      identifying changes of motor output maps, the data from imaging experiments may
      better reflect modulation of inputs to multiple motor areas.

PMID- 11244548
TI  - Abnormal processing of social information from faces in autism.
AB  - Autism has been thought to be characterized, in part, by dysfunction in emotional
      and social cognition, but the pathology of the underlying processes and their
      neural substrates remain poorly understood. Several studies have hypothesized
      that abnormal amygdala function may account for some of the impairments seen in
      autism, specifically, impaired recognition of socially relevant information from
      faces. We explored this issue in eight high-functioning subjects with autism in
      four experiments that assessed recognition of emotional and social information,
      primarily from faces. All tasks used were identical to those previously used in
      studies of subjects with bilateral amygdala damage, permitting direct
      comparisons. All subjects with autism made abnormal social judgments regarding
      the trustworthiness of faces; however, all were able to make normal social
      judgments from lexical stimuli, and all had a normal ability to perceptually
      discriminate the stimuli. Overall, these data from subjects with autism show some
      parallels to those from neurological subjects with focal amygdala damage. We
      suggest that amygdala dysfunction in autism might contribute to an impaired
      ability to link visual perception of socially relevant stimuli with retrieval of
      social knowledge and with elicitation of social behavior.

PMID- 11244549
TI  - Different brain mechanisms mediate sensitivity to sensory consonance and harmonic
      context: evidence from auditory event-related brain potentials.
AB  - The goal of this study was to analyze the time-course of sensory (bottom-up) and
      cognitive (top-down) processes that govern musical harmonic expectancy. Eight
      chord sequences were presented to 12 musicians and 12 nonmusicians. Expectations
      for the last chord were manipulated both at the sensory level (i.e., the last
      chord was sensory consonant or dissonant) and at the cognitive level (the
      harmonic function of the target was varied by manipulating the harmonic context
      built up by the first six chords of the sequence). Changes in the harmonic
      function of the target chord mainly modulate the amplitude of a positive
      component peaking around 300 msec (P3) after target onset, reflecting top-down
      influences on the perceptual stages of processing. In contrast, changes in the
      acoustic structure of the target chord (sensory consonance) mainly modulate the
      amplitude of a late positive component that develops between 300 and 800 msec
      after target onset. Most importantly, the effects of sensory consonance and
      harmonic context on the event-related brain potentials associated with the target
      chords were found to be independent, thus suggesting that two separate processors
      contribute to the building up of musical expectancy.

PMID- 11244550
TI  - A model of saccade initiation based on the competitive integration of exogenous
      and endogenous signals in the superior colliculus.
AB  - Significant advances in cognitive neuroscience can be achieved by combining
      techniques used to measure behavior and brain activity with neural modeling. Here
      we apply this approach to the initiation of rapid eye movements (saccades), which
      are used to redirect the visual axis to targets of interest. It is well known
      that the superior colliculus (SC) in the midbrain plays a major role in
      generating saccadic eye movements, and physiological studies have provided
      important knowledge of the activity pattern of neurons in this structure. Based
      on the observation that the SC receives localized sensory (exogenous) and
      voluntary (endogenous) inputs, our model assumes that this information is
      integrated by dynamic competition across local collicular interactions. The model
      accounts well for the effects upon saccadic reaction time (SRT) due to removal of
      fixation, the presence of distractors, execution of pro- versus antisaccades, and
      variation in target probability, and suggests a possible mechanism for the
      generation of express saccades. In each of these cases, the activity patterns of
      "neurons" within the model closely resemble actual cell behavior in the
      intermediate layer of the SC. The interaction structure we employ is instrumental
      for producing a physiologically faithful model and results in new insights and
      hypotheses regarding the neural mechanisms underlying saccade initiation.

PMID- 11244551
TI  - Relative shift in activity from medial to lateral frontal cortex during
      internally versus externally guided word generation.
AB  - Goldberg (1985) hypothesized that as language output changes from internally to
      externally guided production, activity shifts from supplementary motor area (SMA)
      to lateral premotor areas, including Broca's area. To test this hypothesis, 15
      right-handed native English speakers performed three word generation tasks
      varying in the amount of internal guidance and a repetition task during
      functional magnetic resonance imaging (fMRI). Volumes of significant activity for
      each task versus a resting state were derived using voxel-by-voxel repeated
      measures t tests (p <.001) across subjects. Changes in the size of activity
      volumes for left medial frontal regions (SMA and pre-SMA/BA 32) versus left
      lateral frontal regions (Broca's area, inferior frontal sulcus) were assessed as
      internal guidance of word generation decreased and external guidance increased.
      Comparing SMA to Broca's area, Goldberg's hypothesis was not verified. However,
      pre-SMA/BA 32 activity volumes decreased significantly and inferior frontal
      sulcus activity volumes increased significantly as word generation tasks moved
      from internally to externally guided.

PMID- 11244552
TI  - The limits of counting accuracy in distributed neural representations.
AB  - Learning about a causal or statistical association depends on comparing
      frequencies of joint occurrence with frequencies expected from separate
      occurrences, and to do this, events must somehow be counted. Physiological
      mechanisms can easily generate the necessary measures if there is a direct, one
      to-one relationship between significant events and neural activity, but if the
      events are represented across cell populations in a distributed manner, the
      counting of one event will be interfered with by the occurrence of others.
      Although the mean interference can be allowed for, there is inevitably an
      increase in the variance of frequency estimates that results in the need for
      extra data to achieve reliable learning. This lowering of statistical efficiency
      (Fisher, 1925) is calculated as the ratio of the minimum to actual variance of
      the estimates. We define two neural models, based on presynaptic and Hebbian
      synaptic modification, and explore the effects of sparse coding and the relative
      frequencies of events on the efficiency of frequency estimates. High counting
      efficiency must be a desirable feature of biological representations, but the
      results show that the number of events that can be counted simultaneously with
      50% efficiency is fewer than the number of cells or 0.1-0.25 of the number of
      synapses (on the two models) - many fewer than can be unambiguously represented.
      Direct representations would lead to greater counting efficiency, but distributed
      representations have the versatility of detecting and counting many unforeseen or
      rare events. Efficient counting of rare but important events requires that they
      engage more active cells than common or unimportant ones. The results suggest
      reasons that representations in the cerebral cortex appear to use extravagant
      numbers of cells and modular organization, and they emphasize the importance of
      neuronal trigger features and the phenomena of habituation and attention.

PMID- 11244554
TI  - A population density approach that facilitates large-scale modeling of neural
      networks: extension to slow inhibitory synapses.
AB  - A previously developed method for efficiently simulating complex networks of
      integrate-and-fire neurons was specialized to the case in which the neurons have
      fast unitary postsynaptic conductances. However, inhibitory synaptic conductances
      are often slower than excitatory ones for cortical neurons, and this difference
      can have a profound effect on network dynamics that cannot be captured with
      neurons that have only fast synapses. We thus extend the model to include slow
      inhibitory synapses. In this model, neurons are grouped into large populations of
      similar neurons. For each population, we calculate the evolution of a probability
      density function (PDF), which describes the distribution of neurons over state
      space. The population firing rate is given by the flux of probability across the
      threshold voltage for firing an action potential. In the case of fast synaptic
      conductances, the PDF was one-dimensional, as the state of a neuron was
      completely determined by its transmembrane voltage. An exact extension to slow
      inhibitory synapses increases the dimension of the PDF to two or three, as the
      state of a neuron now includes the state of its inhibitory synaptic conductance.
      However, by assuming that the expected value of a neuron's inhibitory conductance
      is independent of its voltage, we derive a reduction to a one-dimensional PDF and
      avoid increasing the computational complexity of the problem. We demonstrate that
      although this assumption is not strictly valid, the results of the reduced model
      are surprisingly accurate.

PMID- 11244555
TI  - A complex cell-like receptive field obtained by information maximization.
AB  - The energy model (Pollen & Ronner, 1983; Adelson & Bergen, 1985) for a complex
      cell in the visual cortex is investigated theoretically. The energy model
      describes the output of a complex cell as the squared sum of outputs of two
      linear operators. An information-maximization problem to determine the two linear
      operators is investigated assuming the low signal-to-noise ratio limit and a
      localization term in the objective function. As a result, two linear operators
      characterized by a quadrature pair of Gabor functions are obtained as solutions.
      The result agrees with the energy model, which well describes the shift-invariant
      and orientation-selective responses of actual complex cells, and thus suggests
      that complex cells are optimally designed from an information-theoretic
      viewpoint.

PMID- 11244556
TI  - Self-organization of topographic mixture networks using attentional feedback.
AB  - This article proposes a neural network model of supervised learning that employs
      biologically motivated constraints of using local, on-line, constructive
      learning. The model possesses two novel learning mechanisms. The first is a
      network for learning topographic mixtures. The network's internal category nodes
      are the mixture components, which learn to encode smooth distributions in the
      input space by taking advantage of topography in the input feature maps. The
      second mechanism is an attentional biasing feedback circuit. When the network
      makes an incorrect output prediction, this feedback circuit modulates the
      learning rates of the category nodes, by amounts based on the sharpness of their
      tuning, in order to improve the network's prediction accuracy. The network is
      evaluated on several standard classification benchmarks and shown to perform well
      in comparison to other classifiers.

PMID- 11244557
TI  - Auto-SOM: recursive parameter estimation for guidance of self-organizing feature
      maps.
AB  - An important technique for exploratory data analysis is to form a mapping from
      the high-dimensional data space to a low-dimensional representation space such
      that neighborhoods are preserved. A popular method for achieving this is
      Kohonen's self-organizing map (SOM) algorithm. However, in its original form,
      this requires the user to choose the values of several parameters heuristically
      to achieve good performance. Here we present the Auto-SOM, an algorithm that
      estimates the learning parameters during the training of SOMs automatically. The
      application of Auto-SOM provides the facility to avoid neighborhood violations up
      to a user-defined degree in either mapping direction. Auto-SOM consists of a
      Kalman filter implementation of the SOM coupled with a recursive parameter
      estimation method. The Kalman filter trains the neurons' weights with estimated
      learning coefficients so as to minimize the variance of the estimation error. The
      recursive parameter estimation method estimates the width of the neighborhood
      function by minimizing the prediction error variance of the Kalman filter. In
      addition, the "topographic function" is incorporated to measure neighborhood
      violations and prevent the map's converging to configurations with neighborhood
      violations. It is demonstrated that neighborhoods can be preserved in both
      mapping directions as desired for dimension-reducing applications. The
      development of neighborhood-preserving maps and their convergence behavior is
      demonstrated by three examples accounting for the basic applications of self
      organizing feature maps.

PMID- 11244558
TI  - Exponential convergence of delayed dynamical systems.
AB  - We discuss some delayed dynamical systems, investigating their stability and
      convergence. We prove that under mild conditions, these delayed systems are
      global exponential convergent.

PMID- 11244560
TI  - Learning Hough transform: a neural network model.
AB  - A single-layered Hough transform network is proposed that accepts image
      coordinates of each object pixel as input and produces a set of outputs that
      indicate the belongingness of the pixel to a particular structure (e.g., a
      straight line). The network is able to learn adaptively the parametric forms of
      the linear segments present in the image. It is designed for learning and
      identification not only of linear segments in two-dimensional images but also the
      planes and hyperplanes in the higher-dimensional spaces. It provides an efficient
      representation of visual information embedded in the connection weights. The
      network not only reduces the large space requirement, as in the case of classical
      Hough transform, but also represents the parameters with high precision.

PMID- 11244561
TI  - A constrained EM algorithm for independent component analysis.
AB  - We introduce a novel way of performing independent component analysis using a
      constrained version of the expectation-maximization (EM) algorithm. The source
      distributions are modeled as D one-dimensional mixtures of gaussians. The
      observed data are modeled as linear mixtures of the sources with additive,
      isotropic noise. This generative model is fit to the data using constrained EM.
      The simpler "soft-switching" approach is introduced, which uses only one
      parameter to decide on the sub- or supergaussian nature of the sources. We
      explain how our approach relates to independent factor analysis.

PMID- 11244562
TI  - Emergence of memory-driven command neurons in evolved artificial agents.
AB  - Using evolutionary simulations, we develop autonomous agents controlled by
      artificial neural networks (ANNs). In simple lifelike tasks of foraging and
      navigation, high performance levels are attained by agents equipped with fully
      recurrent ANN controllers. In a set of experiments sharing the same behavioral
      task but differing in the sensory input available to the agents, we find a common
      structure of a command neuron switching the dynamics of the network between
      radically different behavioral modes. When sensory position information is
      available, the command neuron reflects a map of the environment, acting as a
      location-dependent cell sensitive to the location and orientation of the agent.
      When such information is unavailable, the command neuron's activity is based on a
      spontaneously evolving short-term memory mechanism, which underlies its apparent
      place-sensitive activity. A two-parameter stochastic model for this memory
      mechanism is proposed. We show that the parameter values emerging from the
      evolutionary simulations are near optimal; evolution takes advantage of seemingly
      harmful features of the environment to maximize the agent's foraging efficiency.
      The accessibility of evolved ANNs for a detailed inspection, together with the
      resemblance of some of the results to known findings from neurobiology, places
      evolved ANNs as an excellent candidate model for the study of structure and
      function relationship in complex nervous systems.

PMID- 11244563
TI  - HNF-3 beta, C/EBP beta, and HNF-4 act in synergy to enhance transcription of the
      human apolipoprotein B gene in intestinal cells.
AB  - Recently, we identified a 315-bp intestinal enhancer (IE), localized over 55 kb
      upstream from the transcriptional start of the human apolipoprotein B (apoB)
      gene, that confers expression of human apoB transgenes in the intestines of mice.
      Four functional binding sites for the intestine-enriched transcription factors
      hepatocyte nuclear factor (HNF)-3beta, CAAT enhancer binding protein (C/EBP)beta,
      and HNF-4 were demonstrated within the 315-bp IE. In this report, we extend these
      earlier studies and examine the relative contributions of these three
      transcription factors to the activity of the enhancer as well as their mechanism
      of interaction with one another. Cotransfection experiments with the expression
      vectors for HNF-3beta, C/EBPbeta, and HNF-4 revealed that HNF-3beta bound to Site
      1, C/EBPbeta bound to Site 2, and HNF-4 bound to Site 3 within the 315-bp IE and
      that the sites act synergistically to enhance intestinal expression of apoB. Each
      one of these four binding sites was mutated, and mutant constructs were
      transfected into intestine-derived CaCo-2 cells to evaluate the role of each of
      these binding sites in enhancer activity. The results of the mutagenesis
      experiments confirmed that the HNF-3beta and HNF-4 sites are most important for
      the enhancer activity, followed by C/EBPbeta Site 2. All three factors bound to
      Sites 1, 2, and 3 must act synergistically for optimal activity of the apoB IE.

PMID- 11244564
TI  - Hepatitis B viral X protein overcomes inhibition of E2F1 activity by pRb on the
      human Rb gene promoter.
AB  - Hepatitis B virus X (HBx) protein is known as an oncogenic transactivator, E2F1
      as a positive regulator of the cell cycle, and pRb as a tumor suppressor. Here,
      we investigated the functional interactions of these proteins on the human Rb
      promoter. Interestingly, HBx transactivated the Rb promoter cooperatively with
      E2F1 in HepG2 cells but not in HeLa cells, in which the functions of p53 and pRb
      are inactive. Combinatorial cotransfection analyses in HepG2 cells showed that
      HBx overcame the inhibition of E2F1 activity by pRb but not that by p53. Domain
      analysis showed that aa 47-70 and aa 117-133 of HBx are important for this
      effect. These results suggest that HBx could inhibit the pRb tumor suppressor and
      increase E2F1 activity. Our data support the oncogenic potential of HBx, which
      may cause HBV-infected cells to grow continuously in the development of
      hepatocellular carcinoma.

PMID- 11244565
TI  - Herpesvirus saimiri Tip gene causes T-cell lymphomas in transgenic mice.
AB  - New World primates develop T-cell lymphomas on infection with Herpesvirus
      saimiri. To investigate the oncogenic potential of the Tip gene of Herpesvirus
      saimiri strain C488, we tried to establish transgenic mice that should express
      Tip under control of a constitutive promoter. Although transgene-positive embryos
      were found, lines could not be established. However, using a system in which the
      transgene has to be activated by a Cre recombinase-mediated deletion, we were
      able to obtain several Tip transgenic lines. At high expression levels, the mice
      developed T-cell lymphomas. Thus, Tip can induce lymphomas and is therefore very
      likely responsible for the oncogenicity of Herpesvirus saimiri.

PMID- 11244566
TI  - Identification of domains mediating transcription activation, repression, and
      inhibition in the paired-related homeobox protein, Prx2 (S8).
AB  - Despite the growing information concerning the developmental importance of the
      Prx2 protein, the structural determinants of Prx2 function are poorly understood.
      To gain insight into the transcription regulatory regions of the Prx2 protein, we
      generated a series of truncation mutants. Both the Prx2 response element (PRE)
      and a portion of the tenascin promoter, a downstream target of Prx2, were used as
      reporters in transient transfection assays. This analysis showed that a conserved
      domain (PRX), found in both Prx1 and Prx2, activated transcription in NIH 3T3
      cells. This PRX domain, as well as other functional regions of Prx2, demonstrated
      both cell-specific and promoter-dependent transcriptional regulation. A second
      important region, the OAR (aristaless) domain, which is conserved among 35 Paired
      type homeodomain proteins, was observed to inhibit transcription. Deletion of
      this element resulted in a 20-fold increase of transcription from the tenascin
      reporter in NIH 3T3 cells but not in C2C12 cells. The OAR domain did not function
      as a repressor in chimeric fusions with the Gal4 DNA binding domain in either
      cell type, characterizing it as an inhibitor instead of a repressor. These
      results give insight into the function of the Prx2 transcription factor while
      establishing the framework for comparison with the two isoforms of Prx1.

PMID- 11244567
TI  - Choice of expression vector alters the localization of a human cellular protein.
AB  - The fusion of synthetic epitopes with proteins of interest is an important tool
      in the identification and characterization of recombinant proteins. Several
      mammalian expression vectors are commercially available containing unique
      identification tags or epitopes. These vectors offer a great advantage to
      researchers, as highly specific antibodies and purification resins against these
      specific epitopes are readily available. The tags facilitate immunologic assays
      and the purification of the recombinant proteins. The fusion of these epitopes
      with the recombinant proteins is not expected to alter the behavior of the
      protein of interest. In this report, we demonstrate that the mere expression of a
      cellular protein, hVIP/mov34, which we earlier identified as a cellular HIV-1 Vpr
      ligand, in two different vectors clearly altered its localization pattern in HeLa
      cells. Specifically, cloning of hVIP/mov34 in pcDNA3/HisA resulted in its nuclear
      localization, whereas the expression of this gene from a TOPO cloning expression
      vector, pcDNA3.1/V5/His, resulted in cytoplasmic expression. The native staining
      pattern of hVIP/mov34 using polyclonal antisera raised against hVIP/mov34
      demonstrated cytoplasmic staining. During cloning, other leader sequences
      intended for targeting this protein into a cytoplasmic or a nuclear location were
      not fused to the actual ORF of this protein. Also, the amino acid sequence of the
      fusion region arising from cloning of hVIP/mov34 in both vectors does not match
      any reported NLS sequences. These results indicate that the choice of the
      expression vectors, as well as the position of synthetic epitopes, can
      significantly alter the behavior and the biology of recombinant proteins. This
      result suggests the need for a careful examination of these features when
      characterizing a newly identified protein.

PMID- 11244568
TI  - Molecular analysis of novel Drosophila gene, Gap69C, encoding a homolog of ADP
      ribosylation factor GTPase-activating protein.
AB  - Adenosine diphosphate-ribosylation factor, ARF1, regulates membrane traffic and
      structure in the endoplasmic reticulum-Golgi and endosomal systems. The ARF
      activity, in turn, is regulated by the guanine nucleotide exchange factors and
      GTPase-activating proteins (GAPs). We have cloned by transposon tagging a novel
      Drosophila gene, Gap69C, coding for a putative homolog of ARF1 GTPase-activating
      protein. The GAP69C protein shares an extensive similarity within its N-terminal
      zinc-finger domain with the rat and yeast homologs. This domain is known to be
      required for ARF-GAP activity. The Gap69C is a single-copy gene producing a major
      2.1-kb mRNA throughout development, but its amount is decreased in larvae. The
      eye pigmentation produced by the reporter mini-white gene inserted into the 5'
      UTR of Gap69C suggests that the expression of Gap69C is nonuniform. In situ
      hybridization revealed a high level of Gap69C transcripts in the morphogenetic
      furrow of the eye imaginal disc, where cells are arrested in G(1). Generated by
      the excision of the P-element, the null allele of Gap69C was found to be viable
      and fertile and showed no apparent abnormal phenotype, indicating that Gap69C is
      not essential for fly development. Analysis of the Drosophila genome sequence
      revealed the presence of other genes related to Gap69C. We propose that the
      absence of a distinctive phenotype in Gap69C null mutants is attributable to
      redundancy with other homologs.

PMID- 11244569
TI  - Organization of ribosomal RNA genes from a Loofah witches' broom phytoplasma.
AB  - Using the technique of integrative mapping with three vectors carrying
      chromosomal rDNA sequences, one of two rRNA operons of loofah witches' broom
      (LfWB) phytoplasma was constructed. This is the first complete rRNA operon of a
      phytoplasma to be reported. The operon has a context of 5'-16S-23S-5S-3' with a
      tRNA(Ile) gene in the ITS and tRNA(Val) and tRNA(Asn) genes downstream from the
      5S rRNA gene. Although the other operon has not been cloned, the DNA sequence of
      a PCR-amplified product shows that it has no tRNA(Ile) gene in the ITS region.
      The complete nucleotide sequences of 16S, 23S, and 5S rDNA are 1538, 2864, and
      113 bp, respectively. Five -10-like sequences, but no -35 sequences, were found
      within a 494-bp leader region. There was a TG dinucleotide two nucleotides
      upstream from each -10-like sequence. The existence of a TG dinucleotide at this
      position has been reported to enhance the efficiency of a promoter without a -35
      region. The regions immediately flanking the 5' and 3' ends of 16S and 23S rDNA
      can form long basepaired stems that contain sites for processing by RNase III. No
      obvious sequence for a rho-dependent or rho-independent termination site was
      found downstream from the tRNA(Asn) gene. The transcription may stop within a
      pyrimidine-rich region, as has been reported for several polypeptide-encoding
      genes and rRNA operons of archaeobacteria. The presence of the tRNA genes
      downstream from the 5S rRNA gene in the rRNA operon of LfWB phytoplasma further
      supports the hypothesis that phytoplasmas are phylogenetically closer to
      acholeplasmas than to mycoplasmas. The phylogenetic relatedness of LfWB
      phytoplasma to other phytoplasmas is discussed on the basis of the nucleotide
      sequence of rRNA genes and ITS.

PMID- 11244570
TI  - Russian experience in screening, analysis, and clinical application of novel
      interferon inducers.
AB  - This review describes a long-standing experience of screening for interferon
      (IFN) inducers in Russia. IFN inducers represent a special group of potential
      antiviral compounds. The main requirements for them are (1) high IFN-inducing
      activity, (2) absence of side effects, (3) wide spectrum of antimicrobial
      activity, (4) broad therapeutic security and, (5) good solubility in water and
      biologic liquids. IFN inducers stimulate IFN production in different cells and
      organs, and that determines the strategy for their application. Amixin (OOO
      "Lancepharm," Moscow, Russia) induces IFN-alpha/beta production mostly in T
      cells. Cycloferon (NTFF "Polysan," St. Petersburg, Russia) stimulates B cells and
      macrophages to produce almost pure IFN-alpha. Double-stranded RNA (dsRNA) and
      polyphenols of natural origin stimulate IFN production in different populations
      of immunocytes. Only polymers, such as Larifan (Riga, Latvia), Kagocel
      ("NIARnedicplus," Moscow, Russia), and Ragosin (N.F. Gamaleya Institute, Moscow,
      Russia), induce IFN synthesis in muscles, so they may be effective against
      rabies. Cycloferon, Larifan, and Kagocel, which induce IFN formation in lungs,
      may be effective against influenza and rhinoviral infections. Cycloferon and
      Larifan stimulate IFN production in liver and spleen and may be effective against
      hepatitis B. Oral compounds (Amixin, Kagocel) that stimulate IFN production in
      intestines may be effective against hepatitis A and enteroviral infections. Low
      molecular weight inducers (Amixin, Cycloferon, Kagocel) that penetrate the blood
      brain barrier may be active against viral encephalitis. At present, clinical
      trials of IFN inducers are limited, but in the near future, IFN inducers may be
      used against very different infections and conditions.

PMID- 11244571
TI  - Growth hormone receptor interaction with Jak proteins differs between tissues.
AB  - Janus kinases (Jak) play an important role in the initial steps of cytokine
      receptor signaling. The specificity of the four members of the Jak family (Jak1,
      Jak2, Jak3, and Tyk2) for different cytokine receptors is not fully understood.
      Recent studies have indicated that a specific cytokine receptor can activate
      several Jak and that this may differ between tissues. The growth hormone receptor
      (GHR) is believed to interact predominantly with Jak2, but studies on cell lines
      have shown that it may also induce phosphorylation of Jak1 and Jak3. Little is
      known about the interaction between the GHR and Jak in tissues. Our aim,
      therefore, was to elucidate which Jak interact with the GHR in two target tissues
      for GH, liver and adipose tissue. Western blot analysis showed that all four
      members of the Jak family are present in both rat liver and adipose tissue.
      However, coprecipitation using an anti-GHR antibody revealed that only Jak1 and
      Jak2 were associated with the GHR in these tissues. The relative amount of Jak1
      and Jak2 that coprecipitated with the GHR differed markedly between tissues. In
      the liver, Jak2 dominated, and only a small amount of Jak1 was detected. In
      adipose tissue, at least one third of the coprecipitated Jak was Jak1. This is
      the first study to show that both Jak1 and Jak2 are associated with the GHR in
      rat tissues. The difference in the ratio between GHR-associated Jak1 and Jak2 in
      liver and adipose tissue may indicate that GHR signaling in different tissues
      could differ in terms of Jak specificity.

PMID- 11244572
TI  - Modulation of functional activities of chicken heterophils by recombinant chicken
      IFN-gamma.
AB  - The objective of the present studies was to examine the in vitro effects of
      recombinant chicken interferon-gamma (rChIFN-gamma) on shape change,
      phagocytosis, and the oxidative/nonoxidative killing activities of day-old
      chicken heterophils. Heterophils (4 x 10(6)/ml) were incubated with various
      concentrations of recombinant ChIFN-gamma from both Escherichia coli and
      transfected Cos cells for 2 h at 39 degrees C. The incubation of the neonatal
      heterophils with rChIFN-gamma resulted in significantly greater numbers of cells
      with membrane shape change when compared with the mock-treated heterophils. Both
      Cos cell-derived and E. coli-derived ChIFN-gamma significantly increased (p <
      0.01) the phagocytosis of opsonized or nonopsonized Salmonella enteritidis by the
      neonatal heterophils in a concentration-dependent manner. Incubation with ChIFN
      gamma induced no direct stimulation of the respiratory burst by the chicken
      heterophils but did prime the heterophils for a significantly strengthened
      respiratory burst to subsequent stimulation with opsonized zymosan (OZ). Lastly,
      incubation of the heterophils with ChIFN-gamma primed the cells for a significant
      increase in the release of beta-D-glucuronidase following stimulation with OZ.
      These results show that neonatal avian heterophils can respond to cytokine
      modulation with enhanced functional competence, suggesting that ChIFN-gamma can
      enhance the immune competence of the innate defenses of chickens during the first
      week of life.

PMID- 11244573
TI  - Production of matrix metalloproteinase-9 in CaCO-2 cells in response to
      inflammatory stimuli.
AB  - Matrix metalloproteinase-9 (MMP-9) may play an important role in the development
      of inflammatory bowel disease (IBD). However, the cellular source of MMP-9 in the
      inflamed mucosa of IBD remains unclear. Here we report that MMP-9 mRNA is
      expressed in CaCO-2 cells, an intestinal epithelial cell line, and that its
      expression is upregulated by inflammatory stimuli. Stimulation of CaCO-2 cells
      with interleukin-1beta (IL-1beta) or tumor necrosis factor-alpha (TNF-alpha) led
      to a dose-dependent increase in expression and secretion of MMP-9. In contrast,
      bacterial lipopolysaccharide (LPS) failed to induce expression or secretion of
      MMP-9, suggesting that an inflammatory reaction leading to cytokine release is a
      necessary step for the induction of MMP-9 release in intestinal epithelial cells.
      Additional studies show that induction of MMP-9 mRNA peaked at 16 h of IL-1beta
      stimulation, whereas expression of monocyte chemoattractant protein-1 (MCP-1) and
      IL-8 both peaked at 3 h of stimulation. Treatment of CaCO-2 cells with
      rosiglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-gamma)
      agonist, significantly reduced secretion of MMP-9, indicating that agents that
      activate PPAR-gamma may have therapeutic use in patients with IBD.

PMID- 11244574
TI  - The murine p202 protein, an IFN-inducible modulator of transcription, is
      activated by the mitogen platelet-derived growth factor.
AB  - p202 is a murine interferon (IFN)-inducible protein belonging to a cluster of IFN
      inducible genes (the 200 family) located in a segment of chromosome 1. It is a
      nuclear DNA-binding protein that is able to modulate transcription by interacting
      with a heterogeneous set of transcription factors, including NF-kappaB,
      (p50/p65), AP-1, c-fos, c-jun, and RB-1. The p202 protein is believed to
      attenuate cell growth/proliferation, mainly through the activation of IFN
      stimulated of gene factor 3 (ISGF3), which binds IFN-stimulated response elements
      (ISRE) located in the promoters of type I IFN genes. In this report, we show that
      the p202 gene can also be induced by platelet-derived growth factor (PDGF), a
      mitogen known to drive G(0)-arrested cells toward reentry into the cell cycle.
      PDGF transiently enhances the steady-state mRNA level of p202 and increases the
      p202 protein level independently from IFN signaling, by acting at the
      transcriptional level on its promoter. The kinetics of p202 induction by PDGF are
      faster and more transient than those of IFN. These data identify p202 as a member
      of the IFN-inducible gene family that can be directly regulated by mitogenic
      stimuli.

PMID- 11244575
TI  - Interleukin-1beta gene transcription in U937 cells is modulated by type I
      collagen and cytoskeletal integrity via distinct signaling pathways.
AB  - Type I collagen (Col), an extracellular matrix molecule highly expressed in
      injured tissues, stimulates interleukin-1beta (IL-1beta) expression in monocytic
      cells. Using U937 cells transfected with the human IL-1beta gene promoter
      connected to a reporter gene, we examined how the organizational state of the
      cytoskeleton modulates the expression of IL-1beta after Col stimulation. We found
      the same degree of stimulation of IL-1beta gene transcription in cells exposed to
      Col presented in different fashions (i.e., soluble Col, Col-coated plate, three
      dimensional Col lattice), suggesting that stimulation of IL-1beta is independent
      of the mode of presentation of Col. The Col-stimulated response was associated
      with induction of the transcription factor activator protein-1 (AP-1) and was
      abolished by a protein kinase C (PKC) inhibitor, by a mitogen-activated protein
      kinase (MAPK) inhibitor, and by cotransfection of cells with a competing AP-1
      oligo. Disruption of cytoskeletal organization with colchicine or cytochalasin B
      stimulated IL-1beta gene transcription and enhanced the cells' response to Col.
      The effects of cytochalasin and colchicine were inhibited by the PKC inhibitor
      but were not affected by the MAPK inhibitor or the AP-1 oligo. These findings
      suggest that the cytoskeletal integrity modulates the constitutive and Col
      stimulated transcription of the IL-1beta gene via distinct signaling mechanisms.

PMID- 11244576
TI  - Minute quantities of granulocyte-macrophage colony-stimulating factor prolong
      eosinophil survival.
AB  - Allergic asthma is characterized by pulmonary infiltration and accumulation of
      eosinophils, which is enhanced by granulocyte-macrophage colony-stimulating
      factor (GM-CSF). T cells, fibroblasts, and eosinophils themselves produce GM-CSF,
      suggesting it functions in the lung microenvironment as a survival factor.
      However, the amounts and the mechanism by which GM-CSF supports eosinophil
      survival remain poorly understood. We have previously reported that human
      peripheral blood eosinophils (PBEo) can be transfected with GM-CSF mRNA using
      particle-mediated gene transfer (PMGT). Using this technology, GM-CSF mRNA was
      introduced into resting PBEo, and GM-CSF production and cell survival were
      assessed. GM-CSF protein was undetectable (< 1 pg/ml) in the supernatant but
      present intracellularly at very low levels. Unexpectedly, the in vitro survival
      of transfected PBEo was 4-fold greater than that of controls. Neutralizing anti
      GM-CSF but not anti-interleukin-5 (anti-IL-5) antibody added up to 24 h after
      transfection abolished enhanced survival, demonstrating that the continuous
      presence of GM-CSF was required. Conditioned medium prepared from transfected
      PBEo prolonged the survival of naive cells. Comparable survival activity was
      mimicked by a single dose of 100-500 pg/ml or multiple administrations of 0.1
      pg/ml recombinant human GM-CSF (rHuGM-CSF). Survival was completely inhibited by
      a Jak2 inhibitor, suggesting that GM-CSF-mediated survival involved signaling
      through the Jak-Stat pathway. Thus, autocrine production of low levels of GM-CSF
      by a minority of PBEo can block apoptosis of the entire culture by a minute but
      sustained GM-CSF release.

PMID- 11244577
TI  - Efficient production of biologically active porcine interleukin-18 by
      coexpression with porcine caspase-1 using a baculovirus expression system.
AB  - We previously reported that the precursor form of porcine interleukin-18 (IL-18)
      expressed by the baculovirus system was able to be secreted efficiently into the
      supernatant of insect cells, whereas only small amounts of mature IL-18 were
      secreted from insect cells. As insect cells do not normally have the IL-1beta
      converting enzyme (caspase-1), which is required for processing of the precursor
      IL-18 into the mature IL-18, we recently cloned porcine caspase-1 cDNA. In this
      study, we constructed a recombinant baculovirus containing the cDNA encoding
      porcine caspase-1 and showed that the coexpression of caspase-1 and the precursor
      IL-18 enabled insect cells to secrete mature IL-18 into the culture supernatant
      efficiently. Moreover, inhibition of caspase-1 activity by its specific inhibitor
      prevented the processing of precursor IL-18 into the mature form. These results
      indicated that the processing and secretion of precursor IL-18 into the mature
      form in insect cells were enhanced by the artificial introduction of caspase-1
      activity for cleavage.

PMID- 11244579
TI  - Human papillomavirus DNA in plasma of patients with cervical cancer.
AB  - BACKGROUND: Human papillomavirus (HPV) is a crucial etiological factor for
      cervical cancer (CC) development. From a diagnostic view-point, the consistent
      presence of HPV in CC allows the viral DNA to be used as a genetic marker. The
      aims of this study were to evaluate the presence, physical status and clinical
      significant of HPV DNA in circulation of CC patients. RESULTS: Whereas 6 out of
      50 (12%) HPV positive CC patients revealed plasma HPV DNA, it was detected in
      none of 20 normal controls or 13 HPV negative CC cases. The plasma DNA exhibited
      an HPV type identical to the HPV in the primary tumors and the DNA from both
      sources was integrated into host genome. Interestingly, several findings
      suggested an association between plasma HPV DNA and metastasis. First, three of
      the HPV DNA positive cases were CC patients with clinical stage IVB or recurrence
      with distance metastases (P = 0.001, RR = 15.67). Second, the amount of plasma
      HPV DNA from metastatic patients to be three times more than three other patients
      without metastases. Finally, the later cases had tendency to develop recurrence
      distant metastases within one year after complete treatment when compared with
      other HPV associated CC patients with the same stage but without the present of
      plasma HPV DNA. CONCLUSIONS: The plasma HPV DNA originated from the CC, was
      associated with metastasis and could be used as a marker representing the
      circulating free CC DNA.

PMID- 11244578
TI  - Relatedness of baculovirus and gypsy retrotransposon envelope proteins.
AB  - BACKGROUND: Current evidence suggests that lepidopteran baculoviruses may be
      divided into two phylogenetic groups based on their envelope fusion proteins. One
      group utilizes gp64, a low pH-dependent envelope fusion protein, whereas the
      other employs a protein family (e.g. LD130 in the Lymantria dispar
      nucleopolyhedrovirus) unrelated to gp64, but that is also low pH-dependent.
      Database searches with members of the LD130 protein family often record
      significant levels of homology to envelope proteins from a number of insect
      retrovirus-like transposable elements of the gypsy class. In this report, the
      significance of the homology between these two types of envelope proteins is
      analyzed. RESULTS: The significance of the alignment scores was evaluated using Z
      scores that were calculated by comparing the observed alignment score to the
      distribution of scores obtained for alignments after one of the sequences was
      subjected to 100 random shuffles of its sequence. These analyses resulted in Z
      scores of >9 for members of the LD130 family when compared to most gypsy envelope
      proteins. Furthermore, in addition to significant levels of sequence homology and
      the presence of predicted signal sequences and transmembrane domains, members of
      this family contain a possible a furin cleavage motif, a conserved motif
      downstream of this site, predicted coiled-coil domains, and a pattern of
      conserved cysteine residues. CONCLUSIONS: These analyses provide a link between
      envelope proteins from a group of insect retrovirus-like elements and a
      baculovirus protein family that includes low-pH-dependent envelope fusion
      proteins. The ability of gypsy retroelements to transpose from insect into
      baculovirus genomes suggests a pathway for the exchange of this protein between
      these viral families.

PMID- 11244580
TI  - The interaction of protein structure, selection, and recombination on the
      evolution of the type-1 fimbrial major subunit (fimA) from Escherichia coli.
AB  - Fimbrial adhesins allow bacteria to interact with and attach to their
      environment. The bacteria possibly benefit from these interactions, but all
      external structures including adhesins also allow bacteria to be identified by
      other organisms. Thus adhesion molecules might be under multiple forms of
      selection including selection to constrain functional interactions or evolve
      novel epitopes to avoid recognition. We address these issues by studying genetic
      diversity in the Escherichia coli type-1 fimbrial major subunit, fimA. Overall,
      sequence diversity in fimA is high (pi = 0.07) relative to that in other E. coli
      genes. High diversity is a function of positive diversifying selection, as
      detected by d(N)/d(S) ratios higher than 1.0, and amino acid residuces subject to
      diversifying selection are nonrandomly clustered on the exterior surface of the
      peptide. In addition, McDonald and Kreitman tests suggest that there has been
      historical but not current directional selection at fimA between E. coli and
      Salmonella. Finally, some regions of the fimA peptide appear to be under strong
      structural constraint within E. coli, particularly the interior regions of the
      molecule that is involved in subunit to subunit interaction. Recombination also
      plays a major role contributing to E. coli fimA allelic variation and estimates
      of recombination (2N(e)c) and mutation (2N(e)mu) are about the same.
      Recombination may act to separate the diverse evolutionary forces in different
      regions of the fimA peptide.

PMID- 11244581
TI  - Aquifex aeolicus 3-deoxy-D-manno-2-octulosonic acid 8-phosphate synthase: a new
      class of KDO 8-P synthase?
AB  - The relationship between 3-deoxy-D-manno-2-octulosonic acid 8-phosphate (KDO 8-P)
      synthase and 3-deoxy-D-arabino-2-heptulosonic acid 7-phosphate (DAH 7-P) synthase
      has not been adequately addressed in the literature. Based on recent reports of a
      metal requiring KDO 8-P synthase and the newly solved X-ray crystal structures of
      both Escherichia coli KDO 8-P synthase and DAH 7-P synthase, we begin to address
      the evolutionary kinship between these catalytically similar enzymes. Using a
      maximum likelihood-based grouping of 29 KDO 8-P synthase sequences, we
      demonstrate the existence of a new class of KDO 8-P synthase, the members of
      which we propose to require a metal cofactor for catalysis. Similarly, we
      hypothesize a class of DAH 7-P synthase that does not have the metal requirement
      of the heretofore model E. coli enzyme. Based on this information and a careful
      investigation of the reported X-ray crystal structures, we also propose that KDO
      8-P synthase and DAH 7-P synthase are the product of a divergent evolutionary
      process from a common ancestor.

PMID- 11244582
TI  - [Epidemiologic methodology of health care analysis of chronic pain patients].

PMID- 11244584
TI  - Magnetic resonance and endoscopic retrograde cholangiopancreatography.

PMID- 11244583
TI  - Lai-like leptospira from the Andaman Islands.
AB  - BACKGROUND & OBJECTIVES: Leptospirosis has been an important public health
      problem in the Andaman Islands since 1988. As information about the exact
      etiological agent is not available, the present study was undertaken to isolate
      and identify Leptospira from human patients. METHODS: An isolate coded AF61 was
      recovered from the blood of a patient clinically suspected to have leptospirosis,
      with fever, headache and body aches as the main symptoms. The isolation was done
      using Ellinghausen-McCullough-Johnson-Harris (EMJH) medium following standard
      procedure. The isolate was identified using microscopic agglutination test (MAT)
      with 'groupsera', cross agglutination absorption test (CAAT) and monoclonal
      antibodies. RESULTS: Agglutination tests with rabbit antisera revealed that the
      isolate belonged to the serogroup icterohaemorrhagiae. The CAAT results showed
      that it was closely related to the serovar lai. Analysis of AF61 with monoclonal
      antibodies confirms our observation with CAAT that it is closely related to the
      reference strain Lai serovar lai. INTERPRETATION & CONCLUSIONS: Serovar lai, has
      been associated with pulmonary haemorrhage in China and Korea. However, the
      strain AF61 was not isolated from a patient with pulmonary symptoms. Further
      studies are needed to understand the possible relationship between serovars and
      clinical patterns and the distribution of serovar lai and lai-like strains in
      Asia.

PMID- 11244585
TI  - Twenty-five years of FEMS. Federation of European Microbiological Societies.

PMID- 11244586
TI  - [Radiofrequency: storm looming over hepatic surgery].

PMID- 11244587
TI  - [Curative treatment of local and regional rectal cancer recurrences].
AB  - How to select patients likely to benefit from reoperation? When a neoadjuvant
      treatment is still feasible, is it useful to perform preoperative radiation or
      chemoradiation? What can be expected after resection of local recurrences in
      terms of survival and quality of life? Does surveillance of patients operated for
      rectal carcinoma influence resectability of local recurrences and results? These
      are the main questions concerning the management of local recurrences after
      resection of a rectal carcinoma.

PMID- 11244588
TI  - [Proximal bile duct cholangiocarcinomas].
AB  - AIM: The aim of this retrospective study was to report a series of 12 patients
      with hilar cholangiocarcinoma treated by curative resection. PATIENTS AND
      METHODS: Between 1980 and 1998, curative resection was performed in 12 patients
      out of 33 patients with a Klatskin's tumor. Preoperative biliary drainage was
      performed in 6 cases. Resection was limited to the extrahepatic bile duct in one
      case only. Resection was extended to the liver in 11 cases including
      segmentectomy I (n = 9), left hepatectomy (n = 7), right hepatectomy (n = 3) and
      segmentectomy IV (n = 1). Postoperative brachytherapy was performed in 3 patients
      combined with conventional radiotherapy. Conventional radiotherapy irradiation
      was performed in 2 patients and was associated with chemotherapy in 1 patient.
      RESULTS: There was no postoperative mortality. Postoperative follow-up was
      uneventful in 5 patients. Actuarial survival rate at 1, 2, 3, and 5 years was 81,
      57, 28 and 28%, respectively. Prolonged survivals (88 and 114 months) were
      observed. CONCLUSION: Hilar cholangiocarcinomas have a poor prognosis. Curative
      resections are usually performed with major liver resections. RM cholangiography
      is now the most efficient examination for selection of surgical indications and
      choice of the best strategy. Long-term survival can be obtained with curative
      surgery. Adjuvant treatment has to be assessed by controlled trials.

PMID- 11244589
TI  - [Cholelithiasis in heart transplant patients].
AB  - The incidence of cholelithiasis is increased in heart transplant recipients.
      STUDY AIM: The aim of this retrospective study was to report a series of 27 heart
      transplant recipients operated for cholelithiasis and to assess the indications
      and safety of cholecystectomy in this population. PATIENTS AND METHODS: Over a 9
      year period, from January 1991 to December 1999, 27 heart transplant recipients
      (21 men and 6 women; mean age: 54.6 years, mainly transplanted for ischemic or
      dilated cardiomyopathy) underwent cholecystectomy. All patients received
      immunosuppressive therapy with a combination of corticosteroids and cyclosporin
      and 10 also received azathioprine. Five patients admitted urgently with calculous
      acute cholecystitis and one patient with previous gastrectomy underwent
      laparotomy, while the other 21 patients were operated by laparoscopy. RESULTS:
      There were no postoperative deaths. In patients operated by laparoscopy, there
      was no conversion to laparotomy and oral immunosuppressive drugs were continued
      without interruption. There was one postoperative hemoperitoneum related to liver
      biopsy performed concomitantly. In patients operated by laparotomy, intravenous
      cyclosporin was necessary until return to bowel function and the only
      complication was a wound abscess. Mean length of hospital stay was 3.1 days after
      laparoscopy and 8.8 days after laparotomy. CONCLUSION: Systematic ultrasound
      screening of cholelithiasis after heart transplantation is necessary because
      cholelithiasis carries a risk of septic complications in these patients.
      Laparoscopic cholecystectomy, associated with a low morbidity, is justified even
      in asymptomatic cases. In patients with acute cholecystitis, "open"
      cholecystectomy must be preferred in order to minimize the risk of biliary
      complications which would be very serious in these immunosuppressed patients.

PMID- 11244590
TI  - [Immediate postoperative complications after a laparoscopic partial posterior
      fundoplication. Early laparoscopic reoperation].
AB  - AIM OF THE STUDY: The immediate postoperative course of laparoscopic partial
      posterior fundoplication can be complicated by severe dysphagia or paraesophageal
      hernia. The aim of this study was to describe the technical causes of these
      complications. PATIENTS AND METHOD: Four patients, operated for gastroesophageal
      reflux disease by laparoscopic partial posterior fundoplication, developed severe
      dysphagia (n = 2) or paraesophageal hernia (n = 2) during the immediate
      postoperative period. A barium swallow examination visualized the complication in
      both cases of dysphagia and in 1 case of paraesophageal hernia. The correct
      diagnosis was established by CT scan in the other case of paraesophageal hernia.
      Reoperations were performed by laparoscopy, 3 days (n = 2) or 6 days (n = 2)
      postoperatively. RESULTS: Dysphagia was due to compression of the esophagus
      against the hiatus by the fundoplication. A new and looser fundoplication was
      easily performed. Dysphagia was no longer present postoperatively. The two
      patients were symptom-free after 6 and 12 months of follow-up, respectively. In
      the cases of paraesophageal hernia, the bottoms of the crura were torn. In the
      patient reoperated 3 days postoperatively, the procedure was easily performed,
      the postoperative course was uneventful and the patient was symptom-free after a
      follow-up of 20 months. In the patient reoperated 6 days postoperatively, the
      upper part of the stomach had moved into the left pleural cavity, the procedure
      was difficult due to inflammation and thickening of the gastric wall, and the
      postoperative course was uneventful, but reflux recurred 18 months later.
      CONCLUSION: When severe dysphagia or paraesophageal hernia occurs during the
      immediate postoperative course of laparoscopic partial posterior fundoplication,
      reoperation, possibly by laparoscopy, identifies and cures the technical defects.
      Based on our experience, we suggest that surgical cure of paraesophageal hernia
      is easier when performed during the immediate postoperative period.

PMID- 11244591
TI  - [Vestigial retrorectal cyst in adults].
AB  - STUDY AIM: The aim of this retrospective study was to report three cases of
      retrorectal vestigial cyst in adults. PATIENTS AND METHOD: From 1977 to 1999
      retrorectal vestigial cyst (RVC) was diagnosed in our department in three women
      who were 28, 57 and 53 years of age, respectively. RVC was revealed by either
      pain (n = 2) that occurred in one case in a pregnant woman, or acute intestinal
      obstruction (n = 1). The patients were operated on using a perineal approach in
      two cases and an abdominal approach in one case. RESULTS: One epidermoid cyst and
      two mixed cysts without any sign of malignancy were observed. Postoperative
      follow-up was simple in two patients, while complications occurred in the third
      one via an uretero-vaginal fistula which required uretero-vesical reimplantation.
      The first two patients, reviewed after a 1-year follow-up, had no functional
      trouble and no sign of recurrence. CONCLUSION: Retrorectal vestigial cysts are
      very rare tumors with a risk for degeneration. Computerized tomography on nuclear
      magnetic resonance and endorectal ultrasonography allow detection of their
      structure and topography and help guide their surgical approach. In the absence
      of malignancy, wide excision, if possible without opening of the cystic wall,
      leads to good results.

PMID- 11244592
TI  - [Repair of midline incisional hernias using the Lazaro da Silva aponeuroplasty
      technique].
AB  - STUDY AIM: The aim of this retrospective study was to assess Lazaro da Silva's
      rectus sheath aponeuroplasty technique for repair of midline incisional hernias
      situated above the arcuate line. PATIENTS AND METHOD: Twenty-six patients
      underwent surgical repair of a supraumbilical (n = 19) or periumbilical (n = 7)
      incisional hernia. Six patients had had repeated laparotomies and two of them had
      recurrent incisional hernia. There were 11 obese patients (42%). Muscle diastasis
      ranged from 4 to 20 centimeters (mean: 9.7 cm). Three overlapping aponeurotic and
      peritoneal layers were used. The peritoneal sac was partially or totally
      incorporated in the repair. RESULTS: There was one postoperative death at day 5
      from acute pancreatitis in a patient with associated cholecystectomy.
      Postoperative complications occurred in six patients. There were 3 abdominal wall
      infections. Obesity was the main factor associated with operative complications
      (p = 0.03). Mean follow-up was 19.1 months. There were 2 recurrences, one of them
      related to an abdominal wall infection. CONCLUSION: The Lazaro da Silva
      aponeuroplasty technique compares favourably with alternative techniques using
      mesh implants. It is indicated for incisional hernias less than 20 centimeters
      wide, situated above the arcuate line.

PMID- 11244593
TI  - [Surveillance after treatment of differentiated thyroid cancers].
AB  - The prognosis of differentiated thyroid carcinoma mainly depends on the quality
      of the initial treatment and on early detection and management of any
      recurrences. STUDY AIM: The aim of this retrospective study was to assess the
      modalities and duration of surveillance in these patients according to an
      original classification based on the initial extent of the tumour. PATIENTS AND
      METHOD: The modalities of detection of local recurrences and metastases and the
      date of the latest recurrences were assessed in a series of 509 patients with a
      mean follow-up of 8.2 years (range: 1 to 25 years). Most patients were treated by
      total thyroidectomy, followed by a therapeutic dose of radioactive iodine. The
      other patients with a small localized carcinoma underwent partial thyroidectomy
      without radioactive iodine. Patients were divided into four groups on the 7th
      postoperative month after follow-up scintigraphy and thyroglobulin assay: group
      I: microcancers (n = 117), group II: cancer without lymph node involvement or
      metastasis and normal thyroglobulin divided into IIA, age < 45 years (n = 100)
      and IIB, age > 45 (n = 94), group III: cancer with lymph node involvement and
      normal thyroglobulin (n = 102), group IV: high-risk cancers with metastases or
      regional extension other than lymph node extension or thyroglobulin > 3
      micrograms/L (n = 96). RESULTS: Cancer-dependent actuarial survival rates for
      groups I, IIA, IIB, III, IV were 100%, 100%, 96%, 100%, and 73% at 10 years and
      100%, 100%, 92%, 100%, and 86% at 15 years, respectively. Local or metastatic
      recurrences were sometimes detected by a single follow-up examination, while the
      other examinations were negative: cervical palpation, thyroglobulin assay, iodine
      scintigraphy, chest X-rays. The latest recurrences were observed at 12 years in
      groups I and IIA and at 16 years in groups IIB, III, and IV with normal
      thyroglobulin. CONCLUSION: This study confirms the importance of weaning
      thyroglobulin assays and scintigraphy which must be repeated every 5 years.
      Cervical palpation, thyroglobulin assay without weaning, chest X-rays may also
      detect recurrences. Duration of follow-up must be adapted to the initial
      extension and subsequent course: 15 years in groups I and IIA, 20 years in groups
      IIB, III, and IV with normal thyroglobulin, for at least 10 years after each
      recurrence, and life-long in the case of progression and thyroglobulin > 3
      micrograms/L. Patients must be informed about the duration of follow-up at the
      7th month when the definitive classification can be established and continuity of
      this follow-up must be documented in a special register.

PMID- 11244594
TI  - [Lymph node mapping and axillary sentinel lymph node biopsy in 243 invasive
      breast cancers with no palpable nodes. The south Lyon hospital center
      experience].
AB  - STUDY AIM: To evaluate the effect of intraoperative lymph node mapping and
      sentinel lymph node dissection (SLND) on the axillary staging of patients with N0
      breast carcinoma. Two techniques were used: blue dye alone (Evans Blue and Patent
      Blue) and combined technique (blue dye and isotope). METHODS: The incidence of
      axillary node metastasis in axillary lymph node dissection (ALND) and SLND was
      compared prospectively. Multiple sections of each SLN were examined by HPS
      staining and immunohistochemical techniques. Two sections of each non sentinel
      node in ALND specimens were examined by routine HPS staining. RESULTS: 243
      patients underwent ALND after SLN biopsy. The SLN detection rate was 225/243
      cases (92.59%): 89.94% with blue dye alone and 100% with the combined technique.
      The false-negative rate was less than 2%. CONCLUSION: SN biopsy is an accurate
      staging technique for N0 breast cancer. SLN biopsy with multiple sections and
      immunohistochemical staining of the SLN can identify significantly more patients
      with lymph node metastases than ALND with routine HPS staining.

PMID- 11244595
TI  - [Caecal-rectal antiperistaltic anastomosis without torsion of the vascular
      pedicle].
AB  - Caecorectal anastomosis by Deloyers' procedure has the disadvantage of creating
      torsion of the vascular pedicle. The technique reported here is a simple
      mechanical anti-peristaltic anastomosis without inversion of the caecum. This
      technique was performed successfully in 26 patients after subtotal colectomy for
      multiple colonic carcinomas or severe constipation.

PMID- 11244596
TI  - [Lateral colostomy with subcutaneous bridge support].
AB  - One hundred and five defunctioning loop colostomies were performed using a
      subcutaneous bridge support. Two complications were observed: a peristomal
      abscess and a bridge migration into the peritoneal cavity. This technique
      facilitates the fitting of stoma appliances. Glass bridge support can be removed
      under local anesthesia. This technique can be recommended in view of the good
      results.

PMID- 11244597
TI  - [Pneumatosis cystoides intestinalis, treated with laparoscopic colectomy].
AB  - The authors report a case of pneumatosis cystoides intestinalis which, after
      failure of medical treatment, was treated by laparoscopic partial colectomy.
      Surgical treatment is a last resort and the laparoscopically-assisted approach
      seems to be a good indication in colectomy for pneumatosis cystoides
      intestinalis.

PMID- 11244598
TI  - [Endometriosis of the rectus abdominis muscles].
AB  - The authors report three cases of endometriosis of the rectus abdominis muscle,
      presenting as a mass of the abdominal wall associated with pain during
      menstruation in women with a history of cesarean section. Treatment consisted in
      wide surgical resection followed by prosthetic abdominal wall repair in one
      recurrent case. Abdominal wall endometriosis is a rare disease that can be
      explained by grafting of endometrial cells to the abdominal wall during
      laparotomy for pelvic surgery, particularly cesarean section. Isolation of the
      abdominal wall during cesarean section and irrigation of the abdominal wall at
      the end of the operation are two theoretical measures designed to prevent
      endometrial cell engraftment. When abdominal wall endometriosis occurs, only
      radical surgical resection can prevent recurrence.

PMID- 11244599
TI  - [Theodor Emil Kocher, modern surgery pioneer].
AB  - Theodore Kocher was awarded the Nobel Prize in 1909 for his work on the
      physiology, pathology and surgery of the thyroid gland. He was the first Swiss
      citizen and the first surgeon to ever receive such a distinction. He was a
      pioneer and a world leader in the surgical revolution of the end of the
      nineteenth century. After graduation in 1865, he traveled in Germany, England,
      France and Austria to observe the work of Langenbeck, Paget, Wells, Nelaton,
      Billroth.... In 1866, he returned to Bern and was appointed assistant in the
      surgical clinic of Lucke. In 1872 he applied for the succession of Lucke. After a
      lively debate, he was appointed by the Board of Regents against the
      recommendation of the faculty who wished to nominate a German surgeon, Konig. It
      proved to be a good choice, as, over a period of 45 years, Kocher developed a
      considerable activity in various fields of surgery leading to world-wide acclaim
      and renown. Kocher's most significant contribution to medicine concerned the
      thyroid gland. He considerably improved thyroid surgery. His anatomical
      knowledge, precise operating technic and respect of the aseptic principles
      defined by Lister, whom he had met in Glasgow, contributed to a reduction of
      mortality from 13% to 0.18%. He described postoperative hypothyroidism, which he
      called cachexia strumipriva and concluded that total thyroidectomy was not
      indicated in benign diseases. When he died, more than 7,000 thyroidectomies had
      been performed in his clinic. Kocher was also interested in orthopedics,
      abdominal and genitourinary surgery, surgical oncology, neurosurgery (Cushing
      conducted experimental research with him). He developed or modified many surgical
      instruments. He conducted a large number of experimental studies and published
      249 articles and books.

PMID- 11244600
TI  - [Nosocomial infections in cancerology].
AB  - Although not specific, nosocomial infections are particularly common in patients
      with solid tumor. Chemotherapy-induced time periods of aplasia are usually of
      short duration and less important than those induced in patients with blood
      tumor. Recent changes regarding cancer therapy are determining factors in regard
      to nosocomial infections: patients are treated in day hospitals that must conform
      to the strictest prevention norms; most of the patients have an indwelling venous
      catheter for months, which may therefore be at the origin of an infection.
      Prevention and education of the nursing staff within the context of a heavy
      workload must be a priority, requiring efforts from everyone in the medical team.

PMID- 11244601
TI  - [Wasting and postoperative infection in cancer patients].
AB  - Denutrition decreases immunological responses of non-cancer patients, the healing
      is altered whereas infectious complications increase. Now during hospitalization,
      malnutrition prevails in cancer patients. The suppression of the adaptability to
      fasting which reduces the expenditure of energy at rest, an a normal metabolic
      response to nutrients' supply with the impossibility to compensate totally the
      metabolic deficits with the artificial nutrition alone, raise the fear of
      postoperative disorders, particularly an increase of the infectious risk. The key
      point is therefore to identify the cachexia's degree owing to a simple,
      predictive and consensual index. This check-up allows a postoperative
      complications' prevention by starting up a perioperative refeeding in high-risk
      subjects: that is to say all severe wasting patients, the people booked for a
      severe surgical procedure, especially for oesophageal and gastric neoplasms.
      Actually, we consider that the quality of the results depend more on the making
      up of the different nutritional solutions dispensed than to strictly providing
      for cancer patients' wants, which could be harmful in the postoperative period.
      Supplementation with antioxidant micronutrients or arginine, glutamine,
      ribonucleic acids and omega-3 fatty acids would allow an immuno- modulation of
      the renutrition. But complications strictly due to preoperative denutrition are
      still to be established.

PMID- 11244602
TI  - [Role of the microbiology laboratory in the diagnosis of nosocomial diarrhea].
AB  - Diarrhea that occurs in hospitalized patients is frequent and may be due to
      infectious or noninfectious causes. In adults with nosocomial diarrhea, the most
      commonly detected agent is Clostridium difficile; in children, rotaviruses are
      predominant. Various studies have shown that bacterial enteric pathogens (e.g.
      Salmonella spp., Shigella spp., Campylobacter spp...) or parasites are common
      causes of community-acquired diarrhea but rarely cause nosocomial enteritis.
      Stool cultures for these pathogens and ova and parasite examination should not be
      performed in patients hospitalized for more than three days unless there are
      plausible clinical or epidemiological reasons to do so. In contrast, C. difficile
      toxins assay (and rotavirus screening in children) should be primarily requested.
      The detection of C. difficile toxin B by stool cytotoxicity assay remains the
      'gold standard'. Identification of toxin A (or A + B) can also be performed by
      immuno-enzymatic (ELISA) tests: results may be obtained in three hours.
      Electronic microscopy is the standard method for rotavirus diagnosis but tests
      using latex agglutination or immuno-enzymatic assay are now available. Various
      typing methods have been developed and may be routinely used in epidemiological
      investigations.

PMID- 11244603
TI  - [Epidemiology, risk factors and prevention of Clostridium difficile nosocomial
      infections].
AB  - Clostridium difficile is responsible for 10-25% of cases of antibiotic-associated
      diarrhea (AAD) and for virtually all cases of antibiotic-associated pseudo
      membranous colitis (PMC). This anaerobic spore-forming bacterium has been
      identified as the leading cause of nosocomial infectious diarrhea in adults.
      Pathogenesis relies on a disruption of the normal bacterial flora of the colon, a
      colonization by C. difficile and the release of toxins A and B that cause mucosal
      damage and inflammation. Incidence of C. difficile intestinal disorders usually
      varies from one to 40 per thousand patient admissions. Risk factors for C.
      difficile-associated diarrhea include antimicrobial therapy, older age (> 65
      years), antineoplastic chemotherapy, and length of hospital stay. Nosocomial
      transmission of C. difficile via oro-fecal route occurs in 3-30% of total patient
      admissions but it remains asymptomatic in more than 66% of cases. Persistent
      environmental contamination and carrying of the organism on the hands of hospital
      staff are common. Measures that are effective in reducing cross-infection consist
      of an accurate and rapid diagnosis, an appropriate treatment, an implementation
      of enteric precautions for symptomatic patients, a reinforcement of hand-washing
      and a daily environmental disinfection. C. difficile is a common cause of
      infectious diarrhea and should be therefore systematically investigated in
      patients with nosocomial diarrhea.

PMID- 11244604
TI  - [Nosocomial diarrhea in adults due to microorganisms other than Clostridium
      difficile].
AB  - Nosocomial diarrhea of the adult is to the largest extend caused by Clostridium
      difficile. However, one must not underestimate the importance of other bacteria
      such as Salmonella or Shigella, which are most common in developing countries.
      Other viruses and parasites can equally be responsible for causing such
      infections.

PMID- 11244606
TI  - [Reference and selective list in hospital hygiene. Impact on practical
      improvement].
AB  - In hospitals, the infection control programs requires a basic policy on selection
      and use of appropriate antibiotics, as well as antiseptics and disinfectants. The
      selective list concept, born in Germany, spread in France during the nineties,
      essentially based on national microbiological standards. With the European free
      circulation of products, more antiseptics and disinfectants with heterogeneous
      status are available to customers, who must settle on the essential data, with
      the help of scientific societies: among these data, efficacy against
      multiresistant strains, adaptation to specific hospital patients, ergonomic
      handling and tolerance today precede economical criteria and supplement the
      European micro-biological standards for antiseptics and disinfectants.

PMID- 11244605
TI  - [Pediatric nosocomial diarrhea].
AB  - Nosocomial diarrhea are an important cause of childhood morbidity and mortality.
      Rotavirus has been recognized as the most important cause of nosocomial
      gastroenteritidis particularly in infants during winter months. Nosocomial
      diarrhea are also, caused by bacterial pathogen like Clostridium difficile,
      Salmonella, Shigella, Campylobacter. Clostridium difficile toxin assay should be
      considered for patients who are receiving antibiotics. Modifications of hygiene
      procedures and preventive measures are necessary in order to reduce nosocomial
      infection.

PMID- 11244607
TI  - [Monitoring the microbiological quality of hemodialysis fluids].
AB  - Microbial quality of hemodialysis fluids seems to be a major short- and long-term
      quality criterion for patients receiving high-efficiency dialysis. Ten years of
      results in Le Mans Dialysis Center of quality monitoring water for hemodialysis,
      dialysate and more recently, acid concentrate are similar to bibliographic data.
      Controlling this quality obviously presupposes: the limitation of contaminating
      feedings from water and from acid concentrate aiming at quasi-sterility and
      apyrogenicity; and the control of biofilm growth inside monitors, ineluctable in
      the actual state of the art.

PMID- 11244608
TI  - [Accreditation of hospital hygiene services by JCAHO].
AB  - For over 50 years, the Joint Commission on Accreditation of Healthcare
      Organizations (JCAHO) has validated the quality of hospital establishments upon
      individual request. During such evaluations, the patient is a primary concern
      with respect to quality standards and issues. Inspection of establishments is
      conducted by healthcare professionals who compare the practices of a specific
      site against 489 standards that act as a system of reference and are published in
      the organization's accreditation manual. The area of hospital hygiene has six
      specific standards that are integrated in the mission to assist healthcare
      activities. The procedures for quality management and performance improvement
      play an essential role in obtaining accreditation.

PMID- 11244609
TI  - In vitro activity of teicoplanin against gram-positive cocci.
AB  - The glycopeptide susceptibility of 443 clinical isolates of gram-positive cocci
      collected from nine general hospitals in 1996 was determined according to the
      recommendations of the CA-SFM (the Antibiogram Committee of the French Society
      for Microbiology). In total, 234 isolates of Staphylococcus aureus, 84 isolates
      of coagulase-negative staphylococci (CNS), 98 enterococci and 27 streptococci
      were collected. The mecA gene confirming resistance to methicillin was found in
      42.7% of S. aureus isolates and 51.2% of CNS isolates. No resistance to
      teicoplanin and vancomycin was found in S. aureus but four isolates of CNS had an
      MIC of teicoplanin > or = 8 mg/L. All isolates of Enterococcus faecalis tested
      were susceptible to both glycopeptides. This study confirms that teicoplanin has
      a very good in vitro activity against gram-positive cocci, isolated in France
      from nosocomial infections.

PMID- 11244611
TI  - Are supplements of ketoacids and amino acids useful in treating patients with
      chronic renal failure?

PMID- 11244610
TI  - Identifying subgroups of the general population that may be susceptible to short
      term increases in particulate air pollution: a time-series study in Montreal,
      Quebec.
AB  - This study was undertaken in order to shed light on which groups of the general
      population may be susceptible to the effects of ambient particles. The objectives
      of the study were (1) to determine whether concentrations of particles in the
      ambient air of Montreal, Quebec, were associated with daily all-cause and cause
      specific mortality in the period 1984 to 1993, and (2) to determine whether
      groups of the population had higher than average risks of death from exposure to
      particles. From the network of fixed-site air pollution monitors in Montreal we
      obtained daily mean levels of various measures of particles, gaseous pollutants,
      and weather variables measured at Dorval International Airport. We also used
      measurements of sulfate from an acid rain monitoring station 150 km southeast of
      the city (Sutton, Quebec). We estimated associations for particulate matter (PM)
      with an aerodynamic diameter of 10 microns or smaller (PM10), or 2.5 microns or
      smaller (PM2.5), total suspended particles (TSP), coefficient of haze (COH), an
      extinction coefficient, and sulfate. Because substantial data for fine particles
      were missing, we developed a regression model to predict PM2.5 and to predict
      sulfate from PM2.5. In the main body of the report, we present results for COH,
      predicted PM2.5, and sulfate. Detailed results for all pollutants are included in
      Appendices H through O, which are available on request from Health Effects
      Institute and from the HEI web site at www.healtheffects.org. To address the
      first objective, we made use of the underlying causes of death among all 140,939
      residents of Montreal who died between 1984 and 1993. We regressed the logarithm
      of daily counts of cause-specific mortality on the daily mean levels for a
      variety of measures of particles, accounting for seasonal and subseasonal
      fluctuations in the mortality time series, overdispersion, and weather factors.
      To address the second objective, we developed algorithms to define conditions
      that subjects had prior to death, with the focus on cardiopulmonary diseases.
      These algorithms were based on information retained on the databases of the
      universal Quebec Health Insurance Plan (QHIP). The databases include records of
      all procedures (e.g., type of surgery), physician visits, and consultations
      carried out by all physicians in Quebec. For persons > or = 65 years and for all
      recipients of social assistance the prescription database contains records of all
      pharmaceuticals dispensed (type of medication, dose, quantity). For each group of
      conditions defined, we used the same statistical model that was used in the
      analyses of all nonaccidental causes of death. In the analyses of cause-specific
      mortality, we found evidence of associations for all nonaccidental causes of
      death and specific causes of death--cancer, coronary artery disease, respiratory
      diseases, and diabetes--that were consistent across most metrics of ambient air
      particle concentrations, evaluated as the 3-day mean of particle concentrations
      measured on the day of death (lag 0) and on each of the two days before death
      (lag 1, lag 2). Associations for all cardiovascular diseases combined were found
      only with sulfate. As well, we generally found increased daily mortality for
      persons 65 years of age and over. The results for all nonaccidental causes of
      death are similar to findings from other studies; the mean percent increase in
      mortality for a 100 micrograms/m3 increase in daily TSP at lag 0 was 6.7%. In the
      analyses of the groups defined from the QHIP data, there was little evidence of
      associations with air pollutants among persons who before death were classified
      as having acute or chronic upper respiratory diseases, airways diseases,
      hypertension, acute coronary artery diseases, and cerebrovascular diseases. On
      the other hand, we found consistent increases across most types of ambient
      particles for persons who had cancer, acute lower respiratory diseases, any form
      of cardiovascular disease, chronic coronary artery diseases, and congestive heart
      failure. As well, we found an association for individuals who did not have any
      cardiovascular disease, lower respiratory diseases, and cancer. This latter group
      consisted of persons who had no interactions with the health care system one year
      before death (12%) and individuals with a wide variety of potentially fatal
      diseases (52%), including neurological conditions (12%), diabetes (8%), cardiac
      dysrhythmias (8%), dementia (6%), organic psychotic disorders (6%), and anemias
      (4%). As statistical power was reduced in the analyses presented above,
      differences between groups (e.g., < 65 and > or = 65 year age groups) were not
      usually statistically significant. The association with diabetes has not been
      reported previously, and this needs to be replicated in other studies. (ABSTRACT
      TRUNCATED)

PMID- 11244612
TI  - [Diagnosis and therapy of eating disorders].
AB  - Even though there is no convincing evidence that eating disorders in general are
      on the rise, there has been an enormous increase in "treated" cases of patients
      with eating disorders. This review will cover important aspects of diagnosis and
      treatment of eating disorders. Psychotherapeutical and pharmacological treatment
      strategies in anorexia and bulimia nervosa will be discussed. For both eating
      disorders, psychotherapy is the treatment of choice. Drugs with a serotonergic
      function, e.g. serotonin-reuptake-inhibitors (SSRI), have demonstrated
      significant results in the treatment of bulimia nervosa and eating disorders with
      comorbid depression. In clinical practice "treatment packages" are offered
      because of the complexity of the disorders. The paper also deals with medical
      complications of eating disorders, motivational interviewing in anorexia nervosa
      and treatment with self-help manuals in bulimia nervosa.

PMID- 11244613
TI  - Effect of a keto acid-amino acid supplement on the metabolism and renal
      elimination of branched-chain amino acids in patients with chronic renal
      insufficiency on a low protein diet.
AB  - The aim of our study was to evaluate the effect of a low-protein diet
      supplemented with keto acids-amino acids on renal function and urinary excretion
      of branched-chain amino acids (BCAA) in patients with chronic renal insufficiency
      (CRI). In a prospective investigation 28 patients with CRI (16 male, 12 female,
      aged 28-66 yrs, CCr 18.6 +/- 10.2 ml/min) on a low-protein diet (0.6 g of protein
      /kg BW/day and energy intake 140 kJ/kg BW/day) for a period of one month were
      included. Subsequently, this low protein diet was supplemented with keto acids
      amino acids at a dose of 0.1 g/kg BW/day orally for a period of 3 months.
      Examinations performed at baseline and at the end of the follow-up period
      revealed significant increase in the serum levels of BCAA leucine (p < 0.02),
      isoleucine (p < 0.03), and valine (p < 0.02) while their renal fractional
      excretion declined (p < 0.02, p < 0.01 resp.). Keto acid-amino acid
      administration had no effect on renal function and on the clearance of inulin,
      para-aminohippuric acid. Endogenous creatinine and urea clearance remained
      unaltered. A significant correlation between fractional excretion of sodium and
      leucine (p < 0.05) and a hyperbolic relationship between inulin clearance and
      fractional excretion of BCAA (p < 0.01) were seen. Moreover, a significant
      decrease in proteinuria (p < 0.02), plasma urea concentration and renal urea
      excretion and a rise in albumin level (p < 0.03) were noted. We conclude that in
      patients with CRI on a low protein diet the supplementation of keto acids-amino
      acids does not affect renal hemodynamics, but is associated--despite increases in
      plasma concentrations--with a reduction of renal amino acid and protein excretion
      suggesting induction of alterations in the tubular transport mechanisms.

PMID- 11244614
TI  - [Birth rate, stillbirth rate and infant mortality of legitimate and illegitimate
      newborn infants in Austria 1987-1996: an ecological study].
AB  - BACKGROUND: The infant mortality in babies of single mothers in Great Britain is
      33% higher than in babies of married mothers. There exists hardly any recent
      publication on infant mortality and stillbirth rate in association with the
      marital state of the mother from other European countries. METHODS: From 1987 to
      1996 birth weight, stillbirth rate and infant mortality of all Austrian
      legitimate and illegitimate births were registered by the Austrian Central
      Statistical Office. Differences between the legitimate and illegitimate newborns
      were analysed. RESULTS: Within the observation period there was a clear overall
      reduction (48%) of infant mortality from 9.8 to 5.1 per 1000. Overall stillbirth
      rate remained stable at 3.7 per 1000 births. The birth weight of illegitimate
      infants was significantly lower and their weighted average stillbirth rate was
      20.4% higher (range -10% to +48%) over the ten year observation period. The
      weighted average infant mortality during the observation period was 24% higher
      (range 0% to +44%) for illegitimate infants. CONCLUSION: In Austria illegitimate
      birth was associated with lower birth weight, higher stillbirth rate and
      increased infant mortality between 1986 and 1997.

PMID- 11244615
TI  - Carotid intima-media thickness in relation to macrovascular disease in patients
      with type 2 diabetes mellitus.
AB  - BACKGROUND: Increased carotid intima-media thickness is regarded as a marker of
      atherosclerosis. Type 2 diabetes mellitus is associated with a high prevalence of
      macrovascular disease. MAIN PURPOSE: The present study aimed to examine the
      relationship between carotid intima-media thickness and the presence of
      macrovascular disease in patients with type 2 diabetes. METHODS: 71 patients with
      type 2 diabetes mellitus were studied. The distal common carotid artery and
      carotid bifurcation intima-media thickness were measured bilaterally with high
      resolution ultrasonography. The relationship between the presence of coronary
      artery disease, cerebrovascular disease and peripheral arterial disease and
      carotid intima-media thickness was evaluated. RESULTS: Patients with coronary
      artery disease had significantly (p = 0.048) increased intima-media thickness of
      the distal common carotid artery. This difference ceased to be significant after
      adjustment for cardiovascular risk factors. Patients with peripheral arterial
      disease had a significantly higher bifurcation (p < 0.0001), distal common
      carotid (p = 0.03) and mean intima-media thickness (p = 0.0008) than did those
      without peripheral arterial disease. This difference remained significant even
      after adjustment for other cardiovascular risk factors. In the multiple linear
      regression analysis, the presence of peripheral arterial disease, age and male
      gender significantly predicted bifurcation intima-media thickness, while age and
      the presence of peripheral arterial disease significantly predicted mean intima
      medial thickness. CONCLUSIONS: In the present study, the increased carotid intima
      media thickness in patients with type 2 diabetes mellitus was related to the
      presence of peripheral arterial disease. This finding probably reflects
      morphologic and hemodynamic similarities between the two vascular beds and
      indicates that increased carotid intima-media thickness in patients with type 2
      diabetes may be a marker of atherosclerosis in different locations.

PMID- 11244616
TI  - Fulminant septic melioidosis after a vacation in Thailand.
AB  - Severe infection with Burkholderia pseudomallei (formerly Pseudomonas
      pseudomallei), the bacterium causing melioidosis, is a common cause of acquired
      septicaemia in south-east Asia and northern Australia. A few cases of infected
      travellers returning to European countries have been reported. Melioidosis is a
      tropical disease, the clinical presentation ranging from asymptomatic infection
      to fulminant sepsis. Predisposing conditions such as impaired cellular immunity,
      preexisting renal failure or diabetes mellitus seem to enhance the severity of
      the disease. For a definite diagnosis the bacterium has to be isolated. The
      antimicrobial treatment of choice is ceftazidime in combination with co
      trimoxazole or doxycycline. Even with correct antibiotic treatment the mortality
      rate is high in cases of fulminant sepsis. We report a 29-year old man with Type
      I diabetes who acquired melioidosis during a vacation in Thailand. After
      returning to Austria he was admitted to the intensive care unit with multiple
      organ failure. Despite intensive care treatment the patient's infection proved
      lethal. Burkholderia pseudomallei was isolated from the blood and bronchoalveolar
      lavage.

PMID- 11244617
TI  - [Aneurysm of the splenic artery: rupture in pregnancy].
AB  - The rupture of a splenic artery aneurysm during pregnancy is a rare event. Two
      thirds of all ruptures happen during the third trimester. We report a case of a
      patient at 39 weeks of gestation suffering from abdominal pain and fetal
      distress. At cesarean delivery an aneurysm of the splenic artery was found to be
      the reason for the hematoperitoneum. Spleen, aneurysm and the tail of the
      pancreas were removed. The patient and her infant survived without further
      damage. Increased blood flow and changes in the vascular wall put pregnant women
      at risk for rupture of an aneurysm. In case of acute abdominal pain accompanied
      by progressive hypotension in a pregnant patient, a rupture of the splenic artery
      has to be considered. Active management and operation are the most important
      procedures for diagnosis and therapy of the bleeding. Abdominal delivery will
      help to establish diagnosis and should be performed immediately.

PMID- 11244618
TI  - [Guidelines of the Austria Section of the International Epilepsy League on the
      health-related capacity for automobile driving (license guidelines) of persons
      with epileptic seizures and other sudden disorders of consciousness].

PMID- 11244619
TI  - [Laparoscopic gastroplasty for severe obesity. 300 cases, evaluation of the first
      150].
AB  - OBJECTIVES: The laparoscopic approach for gastroplasty is gaining widespread
      acceptance for morbid obesity. Less invasive and potentially reversible, this
      gastroplasty guarantees better quality of life. We thus evaluated perioperative
      complications in our consecutive series of 300 patients and followed the
      excessive weight loss (EWL) for the first 150. PATIENTS AND METHODS: Between
      April 1997 and January 2000, 300 patients underwent laparoscopic gastroplasty for
      severe obesity according to the NIH criteria: 266 women, 34 men, mean age 40.1
      years (16-66 years). Mean preoperative weight was 118 kg (85-195 kg) and mean
      body mass index (BMI) was 43.4 kg/m2 (31.5-65.8). Two hundred one patients had
      1.3 comorbidity due to excess weight. The first 150 patients were followed 15.5
      months (12-31) without any lost to follow-up. Medical, dietary and psychological
      data were recorded every 3 months for 18 months. The main evaluation criteria was
      EWL; others were tolerance and morbidity. RESULTS: There was no death. Mean
      operative time was 129 minutes (50-380), mean hospital stay was 4.76 days (3-42).
      There were 11 conversions (3.6%). There were 29 complications (9.6%): 11 were
      postoperative (5 underwent an abdominal operation for 2 perforations, 3 early
      slippages; and 6 respiratory problems with 2 ARDS) and 18 were late complications
      (7 late slippages, 2 incisional hernias and 9 port problems). Follow-up of the
      first 150 patients was complete: at one year, BMI fell from 43.6 to 33.8 kg/m2
      and EWL reached 50.5% at 18 months. CONCLUSION: Our experience is recent, but in
      light of the danger of the spontaneous course of morbid obesity, the results are
      encouraging due to the absence of mortality and the low rate of complications
      after the first 50 procedures. Half of the excess weight can be lost in one and a
      half years. Patient comfort remains quite acceptable with the active support of
      the surgery and medical teams.

PMID- 11244620
TI  - [Incidence and surgical wound infection risk factors in breast cancer surgery].
AB  - BACKGROUND: In order to evaluate occurrence and risk factors for wound infection
      (WI) in breast cancer surgery, we carried out a prospective study. METHODS: From
      September 1996 through April 1997, an infection control physician prospectively
      evaluated 542 wounds of all patients having breast cancer surgery at the Oscar
      Lambret Cancer Center. WI was defined as a wound with pus. Antibiotic prophylaxis
      was given in case of immediate breast reconstruction. Statistical evaluation was
      performed using the c < or = test for categorial data and non-parametric Mann
      Whitney test for continuous data. In univariate analysis, differences were
      considered significant at p < 0.01. RESULTS: The overall WI rate was 3.51%
      (19/352). In univariate analysis, risk factors for WI were: total preoperative
      hospital stay (p = 0.01), previous chemotherapy (p = 0.01), previous oncologic
      surgery (p = 0.03) and immediate breast reconstruction (p = 0.002). In
      mutivariate analysis, we observed two independent predictive factors for WI:
      previous chemotherapy (p = 0.05) and immediate breast reconstruction (p = 0.02).
      CONCLUSIONS: Previous anticancer chemotherapy was a major risk factor. In these
      cases, a phase III trial could confirm efficacy of standard antibiotic
      prophylaxis. Breast reconstruction was the second major risk factor. Standard
      antibiotic prophylaxis (used in our study) was insufficient.

PMID- 11244621
TI  - [Splenic thrombosis and celiac disease: a fortuitous association?].
AB  - BACKGROUND: Rare cases of venous thrombosis associated with celiac disease have
      been reported. CASE REPORT: We report a case of 40-year-old woman with splenic
      infarction and splenic venous thrombosis associated with celiac disease. This
      patient was homozygous for the C677T mutation of the methyltetrahydrofolate
      reductase (MTHFR) gene and had moderately elevated homocysteinemia. DISCUSSION:
      We discuss the link between celiac disease and thrombosis as well as the interest
      and appropriate duration of anticoagulation and hypothesize a mechanism of
      thrombotic disease in this setting with hyperhomocyseinemia.

PMID- 11244622
TI  - [Cerebellar infarction after sclerotherapy for leg varicosities].

PMID- 11244623
TI  - [Masseter pain: an little known, undesirable effect of iloprost].

PMID- 11244624
TI  - [Gynecomastia appearing during myeloma: role of melphalan?].

PMID- 11244625
TI  - [Metastatic nephrocarcinoma: regression after peripheral lymphocyte
      transplantation from compatible donors].

PMID- 11244626
TI  - [Application of the causal theory of action through analysis of therapeutic non
      observance].
AB  - This paper presents an analysis of an aspect of non-observance in the treatment
      of type 1 diabetes mellitus, the absence of adaptation of insulin dosage in spite
      of hyperglycemia. The adaptation of insulin dosage by the patient is described as
      an intentional action, performed as a habit. The problem is analysed through the
      causal theory of action and the concept of akrasia. These considerations may be
      useful to understand other aspects of therapeutic non-observance.

PMID- 11244628
TI  - [The value of angiotensin II].

PMID- 11244627
TI  - [Concerning hyperglycerolemias].

PMID- 11244629
TI  - [Piercing and its infectious complications. A public health issue in France].
AB  - CHARACTERISTIC FEATURES: Piercing, an act that modifies  the body, has progressed
      considerably in France over the last few years. The population involved has grown
      and become more diversified. Performed with a solid needle or a catheter, a wide
      variety of anatomic localizations are concerned, particularly the nose, ears, and
      navel. The shape of the "rings", generally made of surgical steel, niobium or
      titanium, varies greatly. Wound healing by epithelialisation can take up to
      several months. INFECTIOUS RISK: Between 10% and 20% of all piercings lead to a
      local infection. The most commonly found causal agests are Staphylococcus aureus,
      group A Streptococcus and Pseudomonas sp. These germs can cause severe life
      threatening complications even in common localizations (earlobe). Viral
      transmission is another risk (hepatitis B, hepatitis C, hepatitis delta, HIV). A
      few cases of fatal fulminant hepatitis have been described immediately after
      piercing. SAFETY MEASURES: Generally performed under less than desirable sanitary
      conditions, safety measures are needed for piercing. Among professional
      "piercers", a certain number have emphasized the need for providing their clients
      with safer services. The prevention of infection risk should be a priority for
      all. Work along this line has been done in the United States and Canada. In light
      of the impact on public health, it is important to rapidly develop guidelines and
      regulations for piercing in France. Both professional piercers and health care
      workers should participate in developing these safety measures in order to assure
      their implementation.

PMID- 11244630
TI  - [Heterogeneity of nephropathies in type 2 diabetes].
AB  - DIVERSE KIDNEY DISORDERS: Patients with type 2 diabetes mellitus who develop
      nephropathy can have various types of disorders capable of progressively
      destroying the kidneys. It is now clear that the same type of diffuse or nodular
      glomerulosclerosis develops irrespective of the type of diabetes, i.e. the
      pathophysiology of hyperglycemia. HETEROGENEITY: There is however a certain
      degree of heterogeneity in terms of clinical presentation, clinical course and
      response to treatment. Heterogeneity is due to age, the number of different
      accumulated risk factors and disease states, genetic factors that are in the
      process of being identified, and finally, lesions to the urologic apparatus, the
      arteries, and the renal parenchyma itself that are not directly caused by
      diabetes. PRACTICAL IMPACT: Mixed lesions, due to both diabetic and non-diabetic
      causes, may therefore exist in the same kidney. These different possibilities
      should be systematically considered in order to adopt an individualized
      investigative and therapeutic attitude for each new patient.

PMID- 11244631
TI  - [Emergency hormonal contraception in France in 2000].

PMID- 11244632
TI  - [Postpartum hemorrhage: treatment by embolization].

PMID- 11244633
TI  - [Umbilical cutaneous metastasis (or Sister Mary Joseph's nodule) disclosing an
      ovarian adenocarcinoma].
AB  - In this study, the case is described of an umbilical metastasis as the presenting
      symptom of an ovarian adenosarcoma. The overall frequency of cutaneous metastases
      has been estimated at between 5 and 9%. Umbilical metastases are a rare
      occurrence: it is estimated that between 1 and 3% of patients with abdomino
      pelvic disease present with an umbilical nodule. Epidemiological studies have
      shown the female predominance of this disease. The clinical characteristics of
      umbilical metastases cannot be visually distinguished from those of primary
      lesions. The clinical appearance is often that of a nodule of varying size, more
      or less painful, and sometimes ulcerated or suppurating as in the present case.
      The nodule may be indicative of cancer, or of cancer recurrence. The most
      frequently encountered histological type is adenocarcinoma (about 75% of cases),
      and is more rarely epidermoid, undifferentiated, or carcinoid. Etiological
      findings have indicated a digestive origin in over 55% of cases (stomach, colon,
      rectum, pancreas, in decreasing order of frequency), with a clear male
      predominance; cancers of gynecological origin are the second most frequent
      etiology, with ovarian cancers being the most common (34% of cases). Sister Mary
      Joseph nodule accounts for 60% of all malignant umbilical tumors (primary or
      secondary), and is usually associated with a poor prognosis (mean survival: 10-12
      months). However, patient survival time could be lengthened by aggressive
      therapy, i.e., surgery combined with chemotherapy.

PMID- 11244634
TI  - [Human papillomavirus typing in routine cervical smears. Results from a series of
      3778 patients].
AB  - AIM: As human papillomavirus (HPV) infection is a significant risk factor for
      cervical cancer, the aim of this study was to assess the efficacy of HPV
      detection techniques in predicting the presence or the development of a high
      grade squamous intra epithelial lesion. Additional reasons for carrying out this
      investigation were as follows. It was considered that the clinical value of HPV
      typing may have been underestimated in certain previous reports, which based
      their findings on first-generation assays. Moreover, until the present
      investigation most studies only investigated the cases with abnormal smear
      findings and did not include long-term follow-up, nor detailed follow-up of women
      with a normal smear but positive HPV typing, although this patient subgroup is of
      particular interest. The patient population included 3778 women who underwent
      routine cytological cervical screening and who gave their informed consent to
      participate in this study, consisting of a cervical smear, HPV testing via a
      second-generation Hybrid Capture II assay (which is more sensitive than first
      generation tests, and can detect 18 different HPV types, i.e., 13 oncogenic and
      five non-oncogenic types); and in the case of abnormal smear findings,
      colposcopic examination and directed biopsies of the sites of suspected lesions.
      The women with cytomorphologically normal cervical smears but which who HPV
      positive were reexamined six months later. RESULTS: HPV findings were positive in
      66 cases where the initial smear indicated the presence of a high-grade lesion
      with the diagnosis confirmed by biopsy in 65 cases; in 155 cases (76.1%) where
      the initial smear indicated the presence of a low-grade lesion; in 44 (57.1%) out
      of 77 smears indicating the presence of ASCUS-type (atypical squamous cells of
      undetermined significance) lesions; and in 366 cases (10.5%) of apparently normal
      initial smears. After colposcopy and follow-up, a final diagnosis of high-grade
      lesion was made for 85 patients. All these patients were found to have high-risk
      (oncogene-positive) HPV at the first examination, but in only 65 cases (76.5%)
      was the initial smear indicative of a high-grade lesion. Finally, in the patient
      groups with low-grade or ASCUS-type smear findings or with an apparently normal
      smear, a high-grade lesion was only found in those patients with persistent high
      risk HPV infection. In all, the sensitivity of the Hybrid Capture II assay in
      detecting high-grade lesions was 100% versus 85.9% for standard cytology.
      However, its specificity (86.3%) and positive predictive value were not as high
      as the latter. CONCLUSION: The results of this study indicate that HPV typing via
      this second-generation assay displays good sensitivity for the detection of at
      risk cases, i.e., those involving the presence or development of high-grade
      cervical lesions. However, a number of issues have to be addressed before HPV
      typing is adopted in clinical practice, such as the fairly high HPV prevalence in
      women aged over 60 years, and whether the implications of this are the same as
      for younger age groups. Also, the present cost of complete typing remains too
      high for it to be used on a widespread scale. Nevertheless, HPV typing may have a
      useful role to play in the detection of cervical cancer.

PMID- 11244635
TI  - [Fetal arrhythmias: diagnosis, prognosis, treatment; apropos of 33 cases].
AB  - From October 1993 to February 1998, 33 cases of fetal cardiac arrhythmia were
      investigated by doppler-echocardiography at the Lille infantile and congenital
      cardiology department. Extrasystolic arrhythmias were the most frequently
      encountered disorder (25 fetuses, i.e., 76% of cases: 24 instances of
      extrasystolic auricular arrhythmia and one case of extrasystolic ventricular
      arrhythmia). They were invariably benign, and apart from one case only required
      standard monitoring. Tachycardia was observed in 15% of cases (three cases of
      supraventricular tachycardia [SVT] and two cases of auricular flutter [AF]). In
      no instance was a cardiopathic syndrome noted. A number of efficient treatments
      have been described, but the prognosis is often poor in the presence of hydrops
      fetalis. Direct fetal treatments (cordocentesis) are currently under evaluation,
      and at present can only be used as a last resort. In our series, one fetus died
      15 minutes after transplacental Flecaine (flecainide) administration. Two of the
      three SVT and the two AF cases were successfully treated. Bradycardia, which was
      unassociated with extrasystolic arrhythmia, was found in 9% of cases. It is
      concluded that Flecaine is probably the treatment of choice for supraventricular
      and ventricular fetal tachycardia, as it has no teratogenic effect and crosses
      the placenta at a fetal concentration that is 80% of the maternal level. However,
      the administration of this drug is not without risk. It is known to possess
      certain negative side effects, and its pharmacological profile and maternal and
      fetal health risks have not yet been fully investigated. At present, no entirely
      safe and efficient treatment for fetal cardiac arrhythmia has been found.

PMID- 11244636
TI  - [Role of luteinizing hormone in follicular and corpus luteum physiology].
AB  - Luteinizing hormone (LH) is an hypophyseal glycoprotein involved in both
      follicular maturation and corpus luteum function. During the follicular phase,
      effects of LH must be considered according to the stages of follicular
      development: in the early follicular phase, LH acts through specific receptors,
      constitutively present on thecal cells, for stimulating androgen production.
      Androgens seem to be positively involved in the folliculogenesis in primates.
      Indeed, a positive correlation has been recently established between androgen
      receptor expression and follicular cell proliferation. Furthermore, androgens are
      active through a conversion to estrogens in granulosa cells. Estrogens are needed
      for achieving pregnancy. Thus, a question remains: what in the minimal amount of
      endogenous LH required for an optimal production of oestradiol? Several models
      have been investigated in clinical situations with hypogonadotrophic
      hypogonadism: WHO type I anovulation or GnRH analog-induced hypogonadisms. A
      large majority of these studies conclude that the minimal amount of LH needed
      during the follicular phase is probably low (< 1.5 IU/L of plasma LH level).
      Recent availability of GnRH antagonist will give a new opportunity for evaluating
      this minimal LH threshold. During the late follicular phase, LH plays a biphasic
      role, with a positive effect on steroidogenesis but a negative effect on cell
      proliferation. As suggested by S. Hillier, this negative effect on cell
      proliferation may be relevant to control the rate of follicular growth. One
      study, performed in WHO type I anovulatory patients, seems to confirm this
      assumption but further evaluation is needed to give support to this concept.
      Finally, LH is also involved in corpus luteum function. Due to the short half
      life of LH as compared to hCG, the role of LH must be evaluated according to the
      adjunct therapies. For example, following a long-term GnRH aganist administration
      that constantly induces a profound hypophyseal desensitization, LH administration
      must be repeated to adequately sustain the corpus luteum function. This
      conclusion must be reconsidered with the recent introduction of GnRH antagonists.
      Indeed, according to their short-term effects on LH secretion, it may be presumed
      that a single injection of LH may be effective to maintain an adequate corpus
      luteum function.

PMID- 11244637
TI  - [Effects of hormone replacement therapy for menopause on prognostic factors of
      breast cancer].
AB  - AIM: Hormone replacement therapy (HRT) is widely used by post-menopausal women.
      Although this treatment may slightly increase the incidence of breast cancer,
      more and more cases are diagnosed while women are taking HRT. The purpose of this
      study was to ascertain the influence of HRT on prognostic factors and outcome of
      breast cancer. Data on all breast cancer patients, including precise information
      on HRT, was prospectively and systematically recorded in a data base. PATIENTS
      AND METHODS: From 1990 to 1998, 1223 post-menopausal women fulfilled the
      eligibility criteria for this study. The clinical features, laboratory findings
      and survival rates in 245 HRT users who developed breast cancer while being
      treated were compared with those of 245 matched breast cancer patients who had
      never received HRT. RESULTS: Patients who developed breast cancer during HRT had
      fewer locally advanced cancers and smaller and better-differentiated cancers.
      Estradiol receptivity was quantitatively lower in users. Metastasis-free survival
      were better for the users. CONCLUSION: We conclude that HRT does not affect the
      prognosis of breast cancer. Regular surveillance during HRT allows early
      detection of smaller lesions. The higher number of well-differentiated cancers
      and the distribution of hormone receptivity may reflect interaction between
      neoplastic tissue and exogenous hormones.

PMID- 11244638
TI  - [The First World War and venereal disease morbidity. I. The amplitude of the
      plague].

PMID- 11244639
TI  - [Analogues agonists and antagonists: what is their role outside of fertilization
      in vitro?].

PMID- 11244640
TI  - [Thin layer cytology of the cervix uteri].

PMID- 11244641
TI  - [Controversy: systemic amniocentesis for women 38 years and more? Is it still
      lawful to recommend amniocentesis with the sole criterion being maternal age of
      38 years or more?].

PMID- 11244642
TI  - The rationality of resistance: alternatives for engagement in complex
      emergencies.
AB  - The different conceptualisations of conflict in the complex emergency literature
      have profound implications on the perception of the agency of different groups
      and the prospects for conflict management. While much recent analysis has focused
      on the rational political and economic functions of violence, relatively little
      analysis has focused on why the majority of people chose not to resort to
      violence. Using Foucault's analysis of power relations, a new framework for
      conflict analysis is proposed which includes non-violent resistance as well as
      violence as a means of domination. Non-violent resistance is explored as a
      rational, highly adaptable response to acts of domination. A comprehensive
      understanding of conflict must recognise local forms of resistance and identify
      the barriers and opportunities for the engagement of the international
      humanitarian community with these groups. This engagement can be used to foster
      capacities for the creation of legitimate, inclusive, non-violent political and
      economic processes in the attempt to provide alternatives for everyone in the
      conflict. If the purpose of the study of complex emergencies is to understand the
      nature of various conflicts and, based on that understanding, make
      recommendations for possible routes to conflict management, the analysis of local
      resistance and efforts to foster it must become a major aspect of the research
      agenda.

PMID- 11244643
TI  - Rendering the world unsafe: 'vulnerability' as western discourse.
AB  - Disasters seem destined to be major issues of academic enquiry in the new century
      if for no other reason than that they are inseparably linked to questions of
      environmental conservation, resource depletion and migration patterns in an
      increasingly globalised world. Unfortunately, inadequate attention has been
      directed at considering the historical roots of the discursive framework within
      which hazard is generally presented, and how that might reflect particular
      cultural values to do with the way in which certain regions or zones of the world
      are usually imagined. This paper argues that tropicality, development and
      vulnerability form part of one and the same essentialising and generalising
      cultural discourse that denigrates large regions of world as disease-ridden,
      poverty-stricken and disaster-prone.

PMID- 11244644
TI  - 'Scaling-up' in emergencies: British NGOs after Hurricane Mitch.
AB  - This article examines research on NGO 'scaling-up' in a disaster context and
      links it to a broader discussion on whether scaling-up is a useful concept for
      understanding NGO processes in an emergency. Using concepts of scaling-up from
      development literature, research findings from a study of the responses of
      British NGOs to Hurricane Mitch in Central America are presented. The article
      assesses the extent and type of scaling-up that occurred, constraints faced by
      the agencies and the impact of scaling-up on support to partners. Broader issues
      relating to scaling-up post-Mitch are also explored. The conclusion suggests that
      while the concept of scaling-up is useful, the tendency for its use to refer to
      organisational growth has limited a wider understanding and evaluation of the
      role of Northern NGOs in humanitarian crises.

PMID- 11244645
TI  - East Timor emerging from conflict: the role of local NGOs and international
      assistance.
AB  - International assistance efforts have represented a conundrum for East Timorese
      seeking to assert their new independence and autonomy. While urgent needs have
      been met, local participation, involvement and capacity building have not been
      given adequate attention. This outcome is aptly demonstrated in the case of local
      non-government organisations (LNGOs). This paper specifically examines the role
      of LNGOs in the recovery of East Timor within the international assistance
      programme. It examines the challenges of rehabilitation efforts in East Timor
      with a particular focus on capacity building of East Timorese NGOs as part of a
      broader effort to strengthen civil society. The initial crisis response in East
      Timor highlighted tension between meeting immediate needs while simultaneously
      incorporating civil society actors such as NGOs and communities. It has been
      argued that local NGOs and the community at large were not sufficiently
      incorporated into the process. While it is acknowledged that many local NGOs had
      limited capacity to respond, a greater emphasis on collaboration, inclusion and
      capacity building was desirable, with a view to supporting medium and longer term
      objectives that promote a vibrant civil society, sustainability and self
      management.

PMID- 11244646
TI  - Needs assessment of the displaced population following the August 1999 earthquake
      in Turkey.
AB  - In August 1999 a major earthquake struck north-western Turkey. An assessment
      followed to identify the immediate needs of the displaced population. A random
      cluster sample of displaced families living in temporary shelter outside of
      organised relief camps was designed. Representatives of 230 households from the
      four communities worse affected by the earthquake were interviewed. Most families
      lived in makeshift shelters (84 per cent), used bottled water (91 per cent),
      obtained food from relief organisations (61 per cent), had access to latrines (90
      per cent), had a member on routine medication (53 per cent) and obtained
      information by word of mouth (81 per cent). Many respondents reported having
      family members who were over the age of 65 (32 per cent) or under age three (20
      per cent), who were pregnant (6 per cent), or who had been ill since the
      earthquake (64 per cent). The greatest immediate need reported by most families
      was shelter requirements (37 per cent), followed by food (23 per cent) and
      hygiene requirements (19 per cent). Ten days after the earthquake, basic
      environmental health needs of food, shelter and hygiene still predominated in
      this displaced population. Significant portions may have special needs due to age
      or illness.

PMID- 11244647
TI  - Disaster warning and evacuation responses by private business employees.
AB  - When people are advised that their place of employment is threatened with
      disaster, how do they respond? Interviews with employees (n = 406) of 118
      businesses affected by one of seven recent disasters provide the first answers to
      this question. Multivariate analyses document the key variables that best predict
      variation are: 1) emergent perceptions of risk; 2) time of evacuation from work;
      3) time of evacuation from home; 4) multiple evacuations; and 5) tension between
      work and family commitments. When warned of impending disaster, most employees
      initially responded with denial. Gradually, however, emergent perceptions of risk
      intensified especially among those living in communities in which the least
      amount of disaster planning had occurred or who resided in a mobile home or
      apartment. Highest levels of work and family tensions during these evacuations
      were reported by racial minority employees who had children living at home.
      Policy implications for these and other findings are discussed so as to pin-point
      changes business managers should make that will enable them to provide the
      leadership and compassion expected by employees.

PMID- 11244648
TI  - Fetal cells in maternal circulation. What is the relationship to obstetric
      ultrasound?

PMID- 11244649
TI  - Isolated echogenic foci in the fetal heart as marker of chromosomal abnormality.
AB  - OBJECTIVE: To assess the effect of echogenic foci in the fetal heart on the risk
      for Down's syndrome. DESIGN: Prospective evaluation of fetal echocardiograms at a
      fetal cardiology referral center and systematic postnatal follow-up. A relative
      risk was calculated from the prevalence of echogenic foci in fetuses subsequently
      demonstrated to have trisomy 21 divided by that in normal fetuses. For a subgroup
      of 548 fetuses with echogenic foci but otherwise normal detailed anomaly scans,
      the expected number of trisomy 21 fetuses calculated from maternal age risks was
      compared with the observed number to derive a relative risk for isolated
      echogenic foci. RESULTS: Echogenic foci occurred in 905 of 6904 fetuses scanned,
      but after excluding those referred specifically because of an echogenic focus and
      those with heart defects, the incidence was 9.5%. Overall, echogenic foci were
      more frequent in fetuses with trisomy 21 than those without by a factor of 2.93.
      For the 548 fetuses with echogenic foci but otherwise normal detailed anomaly
      scans, the actual number of trisomy 21 fetuses exceeded that expected on the
      basis of maternal age risks by a factor of 5.54. Combination with data from
      several previous studies suggests a consensus relative risk of about 3.0.
      CONCLUSIONS: Echogenic foci are associated with increased risk of trisomy 21 even
      when present as an isolated finding. Their significance in an individual should
      be interpreted in the light of prior risk assessment based on maternal age and
      results of any first-trimester screening tests. We suggest that the prior risk is
      increased by a factor of 3.0.

PMID- 11244650
TI  - Perinatal diagnosis of cardiac tumors.
AB  - OBJECTIVE: As fetal cardiac tumors are a rare condition, we report the perinatal
      diagnosis and ultrasound findings of 12 cases. METHODS: In 10 cases the tumors
      were identified prenatally by fetal echocardiography; gestational age at
      detection ranged from 22 to 34 weeks. In two symptomatic infants cardiac tumors
      were diagnosed on the first day postpartum; prenatal ultrasound evaluation at 26
      and 38 weeks of gestation did not reveal a cardiac lesion. RESULTS: Six fetuses
      had singular tumors, in six fetuses they were multifocal. The left ventricle was
      most often affected. Termination of pregnancy was chosen in three cases, one in
      association with trisomy 21 and tuberous sclerosis. One intrauterine and three
      neonatal deaths due to cardiac failure occurred. Histopathologic examination
      revealed cardiac rhabdomyoma in six fetuses and fibroma in one case. In the five
      surviving fetuses the size of the tumors spontaneously decreased postpartum.
      Rhabdomyomata were associated with tuberous sclerosis in four out of 11 cases.
      CONCLUSION: Cardiac tumors are detectable as early as 22 weeks of gestation.
      Presenting symptoms may be arrhythmia, dysfunction of the atrioventricular
      valves, pericardial effusion and fetal hydrops. The most common perinatal
      diagnosis is rhabdomyoma, which is often associated with tuberous sclerosis.
      Sequential examination in high risk patients should be considered as most tumors
      increase in size during pregnancy and may become evident in late second and third
      trimester of pregnancy. Postpartum, however, regression of tumor size is common.

PMID- 11244651
TI  - Application of three-dimensional power Doppler ultrasound in prenatal diagnosis.
AB  - OBJECTIVE: To assess the fetal cardiovascular system using three-dimensional
      power Doppler ultrasound (3D-PDU) in normal and abnormal conditions during the
      second half of gestation. SUBJECTS: Forty-five normal fetuses and 87 selected
      pregnancies with different abnormalities involving the vascular system were
      examined. METHODS: The following regions of interest were assessed: placental,
      umbilical, abdominal, renal, pulmonary and intracranial vessels together with the
      heart and great arteries. Equipment used was a commercially available HDI-3000
      and 5000 ultrasound system with integrated 3D-Color Power Angio software. Data
      acquisition was performed by the free-hand technique. Images were reconstructed
      online. In pathological cases, a maximum of three attempts of 3D reconstruction
      was allowed to obtain the information needed. RESULTS: Satisfactory visualization
      of the fetal vascular system using 3D-PDU could be achieved in normal
      pregnancies. The main difficulty during the learning curve was the optimization
      of the power Doppler image prior to 3D data acquisition. Despite good
      visualization conditions, the reconstruction of satisfactory images was only
      possible in 56 out of the 87 (64%) pregnancies with abnormal vascular anatomy.
      These were abnormalities of placenta and umbilical vessels (n = 26), intra
      abdominal and intrathoracic anomalies (n = 12), renal malformations (n = 9),
      central nervous system (n = 4) and cardiac defects (n = 5). The main reasons for
      the lack of information were fetal position and movements, overlapping with
      signals from neighboring vessels as well as technical limitations of the online
      system. Details and figures of the potential field of interest in prenatal
      diagnosis are presented.

PMID- 11244652
TI  - Ductus venosus Doppler study in fetuses with homozygous alpha-thalassemia-1 at 12
      to 13 weeks of gestation.
AB  - OBJECTIVE: Fetuses affected by homozygous alpha-thalassemia-1 are anemic from the
      first trimester of pregnancy. We investigated ductus venosus Doppler velocimetry
      in these affected fetuses at 12-13 weeks of gestation. DESIGN: Prospective
      observational study. SUBJECTS: Women referred for the prenatal diagnosis of
      homozygous alpha-thalassemia-1 before 14 weeks of gestation. METHODS: All fetuses
      underwent pulsed Doppler investigations following color flow mapping at 12 or 13
      weeks of gestation. Homozygous alpha-thalassemia-1 was diagnosed by DNA or
      hemoglobin study. The ductus venosus Doppler indices--Vmax (peak velocity during
      ventricular systole), Vmin (minimum forward velocity during atrial systole), TAMX
      (time-averaged maximum velocity), PIV (pulsatility index for veins, Vmax
      Vmin/TAMX), PLI (preload index, Vmax-Vmin/Vmax) and Vmax/Vmin ratio--were
      compared between the affected fetuses and fetuses unaffected by homozygous alpha
      thalassemia-1. RESULTS: Between June 1998 and October 1999, 102 eligible women
      were recruited. Fetal ductus venosus Doppler study was successful in 96
      pregnancies (94%). Of these, 20 fetuses were affected by homozygous alpha
      thalassemia-1. None of them showed hydropic changes at the time of Doppler study.
      The affected fetuses had significantly higher ducts venosus Vmax (30% increase),
      Vmin (50% increase) and TAMX (20% increase) and significantly lower Vmax/Vmin
      ratio, PIV and PLI values. CONCLUSION: Fetuses affected by homozygous alpha
      thalassemia-1 at 12-13 weeks had increased forward flow velocities in the ductus
      venosus throughout the cardiac cycle. The increase of venous return is consistent
      with our previous report of cardiac dilatation and an increase of cardiac output
      in the affected fetuses at this stage as a compensatory mechanism for anemia and
      hypoxia. However, extensive overlap of the ductus venosus Doppler indices between
      affected and unaffected fetuses precludes its use in predicting anemia at 12-13
      weeks.

PMID- 11244653
TI  - Ultrasonography of the peri- and intraventricular areas of the fetal brain
      between 26 and 36 weeks' gestational age; a comparison with neonatal ultrasound.
AB  - OBJECTIVES: To determine to what extent the peri- and intraventricular areas of
      the fetal brain can be visualized in coronal and sagittal planes using high
      frequency transvaginal ultrasound. DESIGN: In a longitudinal study, fetuses of 30
      low-risk pregnancies were studied at 26, 28, 30, 32, 34 and 36 weeks' gestational
      age. The neonates were examined within the first week of life. Visualization of
      the peri- and intraventricular areas was systematically scored in six coronal and
      five sagittal planes. The degree of echogenicity of the periventricular area was
      assessed. Inter- and intra-observer agreements were calculated. RESULTS: For
      fetuses in the cephalic position, the highest percentages of visualization of the
      planes were obtained between 26 and 32 weeks' gestational age (> 70% in four
      coronal and three sagittal planes). Transient periventricular echodensities were
      observed at 26 and 28 weeks' gestational age in 6/39 observations in the cephalic
      position. Small choroid plexus cysts were found in three fetuses with the changes
      persisting in two until after birth. Seven neonates developed mild
      periventricular echodensities/translucencies not present during fetal
      development. The mean interobserver agreement was 0.77 (95% confidence interval
      (CI) 0.73-0.81). The intra-observer agreement varied between 0.48 and 0.72 (mean
      0.6, 95% CI 0.47-0.75). CONCLUSIONS: Transvaginal ultrasonography can be applied
      as a diagnostic tool to evaluate the peri- and intraventricular areas of the
      fetal brain. Transient periventricular densities can be encountered between 26
      and 28 weeks. Term low-risk neonates may develop transient periventricular
      densities or translucencies.

PMID- 11244654
TI  - The monochorionic twin placenta in vivo is not a black box.

PMID- 11244655
TI  - Reference values of fetal aortic flow velocity waveforms and associated intra
      observer reliability in normal pregnancies.
AB  - OBJECTIVES: It was the aim of the present study to calculate new Doppler
      reference ranges for blood flow velocities (Vmax, Vmean, Vmin) and resistance
      indices (PI, RI) for the fetal descending aorta by automatic waveform analysis.
      DESIGN: Cross-sectional prospective study. SUBJECTS: Nine hundred and twenty-six
      low-risk pregnancies at 18-41 weeks' gestation. METHODS: Aortic blood flow
      velocities were derived with pulsed-wave color Doppler. Measurements were carried
      out at the level of the diaphragm. Reference ranges for the individual measuring
      parameters were constructed based on a growth function from a four-parameter
      class of monotonic continuous functions according to the smallest square
      principle. Further investigated were intra-observer reliability and the influence
      exerted by different measuring sites (aortic arch, diaphragm, below the renal
      vessels) on the aortic Doppler flow spectrum. RESULTS: Although a significant
      increase in aortic blood flow velocity was observed at 18-41 weeks' gestation
      (Vmax = 48.2 cm/s to 110.3 cm/s (P < 0.001), Vmean = 20 cm/s to 47.5 cm/s (P <
      0.001) and Vmin = 7.6 cm/s to 18.6 cm/s (P < 0.001)), there were no significant
      changes in the pulsatility or resistance indices. The resistance indices PI and
      RI as well as absolute blood flow velocities (Vmax, Vmin) were significantly
      lower with increasing distance from the heart. Initial decreases were measured
      between the aortic arch and the diaphragm: PI, 2.34 to 1.87 (P < 0.0001); RI,
      0.87 to 0.79 (P < 0.0001); Vmin: 8.5 cm/s to 15.0 cm/s (P < 0.0001). Furthermore,
      systolic blood flow velocities (Vmax) were decreased below the renal vessels from
      97 cm/s to 64 cm/s (P < 0.0007). No significant changes were recorded in
      intensity-weighted mean flow velocities (Vmean). The intra-observer reliability
      was low, but of no clinical relevance. CONCLUSIONS: At constant measuring
      conditions, the reference ranges for blood flow velocities and resistance indices
      in the fetal aorta calculated by the authors serve as the basis for Doppler
      ultrasound antenatal examinations in a normal patient population and enable the
      early diagnosis of fetal risk.

PMID- 11244657
TI  - Reconstructed measurements produced from ultrasound images using a computerized
      system.
AB  - OBJECTIVE: The aim of this study was to evaluate the feasibility and accuracy of
      reconstructed measurements produced from video-printed ultrasound images. DESIGN:
      Reproduction of reconstructed measurements using designated software and
      comparison of the results with regular measurements derived from the same images.
      SUBJECTS: Seventy regular sonographic examinations of biparietal diameter (BPD)
      and nuchal translucency (NT) thickness. METHODS: The study included 35
      conventional-size (BPD) and 35 small-size (NT) measurements. Each image was
      measured twice during a dynamic ultrasound examination (regular measurements) and
      twice using a computerized system (reconstructed measurements). The latter
      comprised three steps: (i) computerization (computer-generated images by
      scanning); (ii) calibration (using the scale located alongside the image); (iii)
      measurement (placing the calipers at the desired points). RESULTS: All images
      were successfully scanned, and the computer-generated images were of sufficient
      quality for proper measurement. There was no difference between mean values of
      regular and reconstructed BPD measurements, 63.9 mm (3.7 mm, SE) and 63.6 mm (3.8
      mm, SE), respectively. Similarly, mean values of regular NT measurements were
      similar to the reconstructed ones, 1.48 mm (0.09 mm, SE) and 1.49 mm (0.09 mm,
      SE), respectively. Repeated regular BPD and NT measurements exhibited
      repeatability coefficients of 1.6 mm and 0.4 mm, respectively. These values were
      smaller than those obtained by repeated reconstructed measurements of 2.1 mm and
      0.52 mm, respectively. CONCLUSIONS: Reconstructed measurements of ultrasound
      video-printed images are feasible, require modest facilities and exhibit more
      than reasonable accuracy. This option may contribute to medical research, audit,
      quality control and training, as well as to medico-legal issues.

PMID- 11244656
TI  - Reference values of fetal peak systolic blood flow velocity in the middle
      cerebral artery at 19-40 weeks of gestation.
AB  - OBJECTIVES: The objectives of this prospective study were (i) to establish new
      reference values of peak systolic blood flow velocity measurement in the fetal
      middle cerebral artery (MCA-PSV) following validated methodological guidelines
      and (ii) to develop a method to calculate Z-scores of MCA-PSV. PATIENTS AND
      METHODS: Cross-sectional data were obtained from 331 pregnant women between 19
      and 40 weeks' gestation. Reference ranges for MCA-PSV were constructed and for
      each measurement linear regression models were fitted separately to the mean and
      standard deviations (SD) as a function of gestational age. An application to
      calculate Z-scores was developed. A comparison was made between the reference
      ranges produced in our study and those of a previous one. RESULTS: A new chart,
      table of centiles and regression equations of MCA-PSV are presented. Comparison
      of our reference ranges with ones produced in a previous study showed similar 5th
      centile values. However, the values for the 50th and 95th centiles between 19 and
      28 gestational weeks were lower in our study. CONCLUSIONS: We have constructed
      reference ranges for MCA-PSV which, because they are derived from a larger number
      of examinations in the 15-20-week period and because the methodological flaws of
      the previously published study have been eliminated, we consider to be more
      accurate and therefore more useful for clinical practice.

PMID- 11244658
TI  - Ultrasound imaging of the lower urinary system in women after Burch
      colposuspension.
AB  - OBJECTIVE: Most of the relevant surgical procedures employed in the management of
      genuine stress urinary incontinence (GSI) involve the technique of bladder neck
      elevation. The appropriate level of suspension is an important (but frequently
      overlooked) consideration as the clinical consequences of over-correction of the
      posterior angle are voiding dysfunction and urgency symptoms. The aim of our
      study was to compare ultrasound characteristics in women with GSI with those of
      women before and after Burch colposuspension. The findings of our study should
      have implications for GSI management. DESIGN: Prospective randomized clinical
      study at the Department of Obstetrics and Gynecology, Charles University, Prague,
      Czech Republic. SETTING: Department of Obstetrics and Gynecology, Charles
      University, Prague, Czech Republic. METHODS: Seventy women with previously
      untreated GSI (preoperative group) and 52 women (42 of whom had been in the
      preoperative group) who were studied 3-12 months after receiving Burch
      colposuspension (postoperative group) took part in the study. The standard
      transperineal and introital ultrasound scans were performed. The mobility of the
      bladder neck was assessed transperineally with a curved array probe after
      instillation of 300 mL of saline. The bladder was then evacuated and the
      thickness of the urinary bladder wall in the sagittal plane in defined regions
      (base, vertex and anterior wall) was measured. RESULTS: We found significant
      differences in bladder neck position, mobility, and in bladder wall thickness.
      Where symptoms of urgency occurred, the average bladder wall thickness was > 5
      mm, the gamma angle < 40 degrees, and lower bladder neck mobility was evident.
      CONCLUSION: These findings supported our hypothesis that signs of urgency follow
      over-elevation of the bladder neck. These results helped us significantly to
      refine our GSI management.

PMID- 11244659
TI  - Thermal balloon endometrial ablation therapy induces a rise in uterine blood flow
      impedance: a randomized prospective color Doppler study.
AB  - OBJECTIVE: To evaluate the possible hemodynamic changes in uterine blood flow
      using transvaginal color Doppler ultrasonography after thermal balloon
      endometrial ablation therapy. STUDY DESIGN: Prospective randomized study.
      PATIENTS AND METHODS: Twenty-seven pre- and post-menopausal women with either
      menorrhagia or endometrial hyperplasia (no sign of atypia) were randomized to
      receive either thermal balloon ablation therapy (n = 13) or gestagen therapy (n =
      14). In the gestagen therapy group, a 3-month period of medroxy-progesterone
      acetate (10 mg/day) was given to premenopausal women during cycle days 15-24 and
      it was given to postmenopausal women continuously. Thermal balloon endometrial
      ablation therapy was carried out on cycle days 3-8. All the color Doppler
      measurements were also carried out on cycle days 3-8. Flow waveforms were
      obtained from the main branch of the uterine arteries, from arcuate arteries and
      from a subendometrial spiral artery. Doppler flow parameters were used for
      subsequent statistical analysis. The measurements took place before the
      initiation of treatment, on the first postoperative day (thermal ablation group
      only), and 1 month and 6 months after initiation of the study. RESULTS: No within
      group or between-group differences were detected until the time of the last
      measurement 6 months after initiation of the treatment. Between the two
      randomized groups, the pulsatility index (PI) was significantly higher in the
      thermal ablation group in all three arteries in comparison with the gestagen
      group, in which no change in the PI took place. In the thermal ablation group, a
      significant rise from the pretreatment level was observed in the PI in the
      uterine arteries and in the spiral artery 6 months after the therapy. CONCLUSION:
      Thermal balloon endometrial ablation therapy induces a rise in uterine blood flow
      impedance, but not until 6 months after the treatment. The rise in impedance may
      be due to fibrosis in the uterine cavity which thermal balloon therapy has been
      shown to produce.

PMID- 11244661
TI  - Congenital absence of portal vein in the fetus: a case report.
AB  - Congenital absence of portal vein (CAPV) is a rare abnormality, which may be
      associated with other abnormalities. We report a case of prenatal diagnosis of
      absent portal vein confirmed on postnatal ultrasonography and computed tomography
      scan. The ultrasound features of CAPV include dilated intra-abdominal segment of
      umbilical vein, dilated inferior vena cava and the presence of hyperechogenic
      areas in the liver. Blood coming from the umbilical vein directly drains into the
      inferior vena cava. The dilated intra-abdominal segment of the umbilical vein
      shows high velocity pulsatile flow, resembling that of ductus venosus. These
      findings should prompt a careful search for the portal vein and any associated
      anomalies.

PMID- 11244660
TI  - Prediction of preterm delivery in twins by cervical assessment at 23 weeks.
AB  - OBJECTIVE: To establish the relation between cervical length at 23 weeks of
      gestation in twin pregnancies and risk of spontaneous delivery before 33 weeks.
      METHODS: Cervical length was measured by transvaginal sonography at 23 (range 22
      24) weeks of gestation in 464 twin pregnancies attending for routine antenatal
      care. In the patients who were managed expectantly the relation between cervical
      length and the rate of spontaneous delivery before 33 weeks was determined.
      RESULTS: The cervical length distribution was skewed to the left and the median
      value was 36 mm. The rate of spontaneous delivery before 33 weeks was inversely
      related to cervical length at 23 weeks. It increased gradually from about 2.5% at
      60 mm, to 5% at 40 mm and 12% at 25 mm, and exponentially below this length to
      17% at 20 mm and 80% at 8 mm. Cervical length of 20 mm or less is found in about
      8% of the population and this group contained about 40% of women delivering
      spontaneously before 33 weeks. CONCLUSIONS: In twin pregnancies measurement of
      cervical length provides useful prediction of risk for spontaneous early preterm
      delivery.

PMID- 11244662
TI  - Persistent right umbilical vein in a fetus with Noonan's syndrome: a case report.
AB  - We present a case of persistent right umbilical vein with Noonan's syndrome.
      Persistence of the right umbilical vein with no intrahepatic portion is an
      uncommon finding with a review of the literature revealing only five other cases.
      In these cases drainage was directly into the right atrium, inferior vena cava
      (IVC) or IVC via the iliac vein. Of the reported cases Noonan's syndrome was
      confirmed in one case and suspected in a second. This report represents a third
      case of persistent right umbilical vein with confirmed Noonan's syndrome.

PMID- 11244663
TI  - Prenatal diagnosis of umbilical cord aneurysm in a fetus with trisomy 18.
AB  - Aneurysm of the umbilical cord is an extremely rare vascular anomaly. We report a
      case of umbilical cord aneurysm with arteriovenous fistula in a fetus with
      trisomy 18. At 34 weeks' gestation a fetus with suspected intrauterine growth
      restriction and oligohydramnios was referred to our institution. Ultrasound
      examination was confirmatory and additionally revealed multiple markers for
      trisomy 18. In the umbilical cord an aneurysm was diagnosed characterized by a
      cystic lesion with hyperechogenic rim measuring 18 x 18 x 19 mm in diameter.
      Color flow and spectral Doppler examinations showed a jet originating from one of
      the umbilical arteries entering the cystic lesion which appeared to be the
      dilated umbilical vein. Fetal blood sampling and subsequent karyotyping revealed
      trisomy 18 (47, XY, +18). The patient elected to terminate the pregnancy.
      Pathologic examination of placenta and umbilical cord confirmed the prenatal
      diagnosis of umbilical cord aneurysm and arteriovenous fistula. Histology
      demonstrated a strongly dilated umbilical vein, one moderately dilated artery and
      a second, apparently normal artery.

PMID- 11244664
TI  - Antenatal diagnosis of fetal intra-abdominal umbilical vein dilatation.
AB  - Dilatation of the intra-abdominal portion of the fetal umbilical vein is a rare
      abnormality. We describe here a new case diagnosed at 31 weeks of gestation and
      discuss the clinical features and management of this abnormality.

PMID- 11244665
TI  - First trimester prenatal diagnosis of chondroectodermal dysplasia (Ellis-van
      Creveld syndrome) with ultrasound.
AB  - Chondroectodermal dysplasia (Ellis-van Creveld syndrome) is an autosomal
      recessive condition characterized by short-limb dwarfism, postaxial polydactyly,
      ectodermal defects, and congenital heart disease. This condition is most
      prevalent in the Amish population of Lancaster, Pennsylvania, USA, occurring in
      1/5000 births and in 1/60,000 births in the general population. This report
      presents a case of ultrasonographic detection of chondroectodermal dysplasia at
      12 weeks of gestation.

PMID- 11244666
TI  - Picture of the month. Assessment of fetal renal perfusion by power Doppler
      digital analysis.

PMID- 11244667
TI  - Patency of radial arterial catheters.
AB  - BACKGROUND: Data on the influence of flush methods, blood-sampling methods, and
      site location on the patency of radial arterial catheters used for pressure
      monitoring are sparse. OBJECTIVES: To determine the effects of flush and blood
      sampling methods, insertion site, and sex of patients on catheter patency.
      METHODS: In a randomized trial, 174 patients requiring radial arterial pressure
      monitoring were assigned to 4 groups: fast flush as needed and nonwaste blood
      sampling; fast flush as needed and waste blood sampling; fast flush every 4 hours
      and waste blood sampling; and fast flush every 4 hours and nonwaste blood
      sampling. All site locations were evaluated for patency, and all monitoring
      systems were maintained with isotonic sodium chloride solution. RESULTS:
      Nonpatent catheters were 4.23 times more likely in patients with insertion sites
      3 cm or higher above the bend of the wrist than in patients with lower sites (P =
      .01). Duration of patency did not differ between catheters maintained with fast
      flush every 4 hours and those flushed as needed or between catheters according to
      the method of blood sampling. Women were 3.05 times more likely than men to have
      nonpatent catheters (P = .02). With insertion sites 3 cm or higher above the
      radiocarpal joint, nonpatency was 7.3 times more likely in women than in men (P <
      .001). CONCLUSIONS: Insertion sites closest to the bend of the wrist increase
      chances of maintaining patency. Catheters can be maintained with as-needed
      flushes, and either waste or nonwaste blood sampling can be used.

PMID- 11244668
TI  - Risk factors for sternal wound infection in men versus women.
AB  - BACKGROUND: Differences between men and women in complication rates after cardiac
      surgery have been reported. The rate of one of the most severe postoperative
      complications, sternal wound infection, has not been compared between the sexes.
      OBJECTIVE: To compare the frequencies of 21 risk factors for sternal wound
      infection between men and women. METHODS: Records of 306 patients who had cardiac
      surgery between 1989 and 1999 at 3 different hospitals in the southwestern and
      southeastern United States were reviewed for 21 risk factors. Of the 306
      patients, 115 (25 women and 90 men) had experienced a sternal wound infection and
      191 randomly selected patients (52 women and 139 men) had not. RESULTS: Three
      risk factors occurred at significantly different rates in men and women. Smoking
      and use of a single internal mammary artery for grafting were more common in men
      than women. Women were older than men at the time of cardiac surgery. Logistic
      regression analyses showed that the 3 dichotomous risk factors (use of single
      internal mammary artery for grafting, smoking, age > 70 years) that univariate
      analysis indicated were significantly related to sex could also be used to
      predict infection group. CONCLUSIONS: This study contributes to the awareness of
      the possible differences between men and women in the risk of sternal wound
      infection developing after cardiac surgery. Although 3 risk factors occurred at
      significantly different rates in men and women, further research is needed to
      determine the effects that these differences in risk factors may have on the
      occurrence of sternal wound infection in men and women.

PMID- 11244669
TI  - Eisenmenger syndrome: a case study.

PMID- 11244671
TI  - The mysteries of the human genome uncovered--medicine is changed forever.
AB  - It is impossible to overemphasize the significance of the recent announcement
      that 85% of the DNA of the human genome has been decoded. Physicians can now
      begin teasing out the secrets of human health and disease. Within the next 10
      years, it may be possible to determine who may be vulnerable to illnesses like
      Alzheimer's disease, cancer, and diabetes. The world of medicine will be utterly
      transformed in a few decades. Even before decoding of the human genome is
      completed, scientists have begun a new and more challenging research in
      explaining the molecular basis of life. "Proteonomics," the cataloging and
      analysis of every protein in the human body looms as the next major scientific
      medical effort. Proteins are more varied and complex than DNA. Fifty years from
      now, our understanding of the human organism and its various ills will be
      transformed beyond recognition through genomics and proteonomics. Stay tuned!

PMID- 11244672
TI  - Influence of clinicians' values and perceptions on use of clinical practice
      guidelines for sedation and neuromuscular blockade in patients receiving
      mechanical ventilation.

PMID- 11244673
TI  - One solution to poor staffing ratios.

PMID- 11244674
TI  - Quiet time: a nursing intervention to promote sleep in neurocritical care units.
AB  - BACKGROUND: Patients in intensive care units are often sleep deprived, yet little
      research exists on the impact of nursing care on promoting sleep. OBJECTIVES: To
      determine if implementing a "quiet time" protocol to reduce external
      environmental stimuli is associated with increased frequency of sleep among
      patients in a neurocritical care unit. METHODS: Patients were observed 8 times
      each day before and after implementation of a protocol in which environmental
      sounds and lights were decreased from 2 AM to 4 AM and from 2 PM to 4 PM. Data
      collected at 2:45 AM, 3:30 AM, 2:45 PM, and 3:30 PM on patients with scores of 10
      or greater on the Glasgow Coma Scale were analyzed. A total of 2975 observations
      were made on a total of 239 patients: 1446 observations on 118 patients in the
      control group and 1529 observations on 121 patients in the intervention group.
      RESULTS: The percentage of patients observed asleep was significantly higher
      during the months the quite-time period was implemented than during the control
      period before the intervention was started. The increase in sleep behavior was
      associated with decreased sound and light levels achieved during the quiet time.
      Patients observed during the intervention period were 1.6 times more likely to be
      asleep during the quiet time than were patients observed during the control
      period (P < .001). CONCLUSIONS: A concentrated effort by staff to reduce
      environmental stimuli at discrete preset intervals increases the likelihood of
      sleep during scheduled quiet time in the neurocritical care unit.

PMID- 11244675
TI  - Interrater reliability of 2 sedation scales in a medical intensive care unit: a
      preliminary report.
AB  - BACKGROUND: Critical care nurses must assess the effectiveness of sedatives and
      analgesic agents in order to titrate doses. OBJECTIVES: To measure the interrater
      reliability of 2 sedation scales used to assess patients in medical intensive
      care units. METHODS: The interrater reliabilities of the Motor Activity
      Assessment Scale and the Luer sedation scale were compared prospectively in 31
      patients receiving mechanical ventilation in an 18-bed medical intensive care
      unit of a tertiary care institution. Three registered nurses, 1 clinical
      pharmacist, and 1 physician simultaneously and independently followed a
      standardized procedure to rate each patient by using the 2 scales. Scales were
      randomly ordered to counteract ordering effect. Analysis of variance with post
      hoc Duncan multiple range tests was used to detect bias; a correlation
      coefficient matrix was used to examine degree of association among raters; and
      the intraclass correlation coefficient was measured to control for multiple
      raters. RESULTS: No significant bias was detected with either scale. The Motor
      Activity Assessment Scale had less variation (Pearson r = 0.75-0.92) than did the
      Luer scale (Pearson r = 0.37-0.94) and had a stronger intraclass correlation
      coefficient (0.81 vs 0.79). CONCLUSIONS: The Motor Activity Assessment Scale
      showed the highest consistency among raters.

PMID- 11244676
TI  - Hibernating myocardium.
AB  - According to estimates, up to 50% of patients with coronary artery disease and
      impaired left ventricular function have areas of viable myocardium. This
      dysfunctional, yet viable myocardial tissue, which can improve functionally after
      myocardial oxygen supply is reestablished, has been called hibernating
      myocardium. The possible pathophysiological mechanism that leads to hibernating
      myocardium is controversial: is the phenomenon due to persistent ischemia or is
      it the result of repetitive episodes of ischemia and reperfusion, such as
      myocardial stunning? Regardless of the mechanism, the presence of viable
      myocardial tissue indicates that structural and biochemical cellular changes
      occur, and the recovery of left ventricular function after revascularization
      depends on the severity and extent of these changes. Whether these changes
      reflect a long-lasting state of cellular dedifferentiation, an adaptive process
      that is reversible, or eventually lead to cellular degeneration has not been
      determined. Perhaps early detection of hibernating myocardial tissue via
      noninvasive imaging techniques used to assess contractile response, integrity of
      the cellular membrane, myocardial metabolism, and myocardial blood flow and
      subsequent early coronary revascularization may prevent infarction and
      deterioration in left ventricular function. Knowledge that reversible changes and
      areas of viable myocardium can occur in patients with left ventricular
      dysfunction will assist healthcare providers in the care and management of
      patients with hibernating myocardium.

PMID- 11244677
TI  - More than a pump: the endocrine functions of the heart.
AB  - The endocrine functions of all tissues, including the heart, are being delineated
      in more detail as our understanding of cellular biology unfolds. Natriuretic
      peptides form an important counterregulatory system to balance the effects of
      sympathetic neurohormones. As we learn to intervene with therapeutic
      manipulations of this system, critical care practitioners will be involved in the
      assessment, monitoring, and evaluation of new cardiovascular therapies.

PMID- 11244679
TI  - Quality of care: giving consumers a say.
AB  - In this era of market-driven health care, there's a lot of talk about quality,
      but low-income consumers and their advocates have not always been part of that
      discussion. In recent years, many have focused more attention on expanding
      coverage and promoting enrollment. Now that's shifting, and those who've long
      advocated consumer involvement as a way to improve health care for all are
      focusing more on the quality issue. They're discovering that what health plans
      mean by quality often overlooks just those quality-of-care areas that most
      concern consumers. This issue of States of Health looks at quality, and shows how
      an initiative funded by the Nathan B. Cummings Foundation could contribute to a
      health care system in which a fuller, more consumer-oriented definition of
      quality actually counts.

PMID- 11244678
TI  - Comparison of anxiety assessments between clinicians and patients with acute
      myocardial infarction in cardiac critical care units.
AB  - BACKGROUND: Although anxiety is common after acute myocardial infarction and can
      adversely affect physical recovery, it is not part of the routine clinical
      assessment of patients with myocardial infarction. Furthermore, evidence suggests
      that patients and clinicians differ significantly in their assessments of
      patients' anxiety levels. OBJECTIVES: To determine the extent to which clinicians
      assess anxiety in patients with acute myocardial infarction and to compare
      patients' self-ratings with their clinicians' assessments. METHODS: In a
      prospective, descriptive study, 101 patients used the Spielberger State Anxiety
      Index to assess their anxiety during the first 48 hours after admission for acute
      myocardial infarction. Patients' scores were compared with nurses' and
      physicians' assessments of the patients' anxiety as reported in the medical
      record. RESULTS: Only 45 patients (45%) had anxiety assessments noted in the
      record. Of those 45, 26 patients (58%) were described simply as anxious without
      any further description of the level of anxiety. Eleven (24%) of those 45
      patients had behaviors of anxiety recorded, again without any indication of the
      level of anxiety. No association between patients' self-assessments and their
      clinicians' assessments was apparent (lambda = .03; P > .05). CONCLUSIONS:
      Anxiety was not routinely assessed, despite nearly half the patients reporting
      moderate to extreme anxiety when asked. When clinicians assessed anxiety, their
      assessments did not match patients' self-ratings of anxiety. A simple, easy-to
      use instrument for discriminating levels of anxiety is needed.

PMID- 11244680
TI  - [Clinical characteristics of hereditary cerebrovascular disease in a large family
      from Colombia].
AB  - INTRODUCTION: The cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy (CADASIL) is caused by mutations of the Notch3
      gene in the chromosome 19p13.1. and is characterized by small-vessel disease of
      the cerebral. The clinical feature consists of migraine, recurrent strokes, mood
      changes and dementia. OBJECTIVE: To describe the clinical phenotype of a
      Colombian family with hereditary cerebrovascular disease. PATIENTS AND METHODS:
      We performed one pedigree with 268 individuals, neurologic examination to 57
      members and magnetic resonance imaging (MRI) to 25 of them. RESULTS: Clinical
      analysis strongly support the diagnosis of CADASIL because 12 individuals had
      suffered recurrent stroke, five of them later developed subcortical dementia. Two
      patients developed dementia without preceding stroke. All affected individuals by
      stroke or dementia whom were tested with MRI had white matter hyperintensities
      and subcortical infarcts (nine cases). Others seven individuals have MRI signal
      abnormalities like CADASIL, four of them are asymptomatic, one had suffered
      ischemic transient attacks and two had suffered migraine. Other 22 individuals
      had only migraine. We outstand the high frequency of MRI signal abnormalities in
      corpus callosum that we found in five individuals with stroke or dementia, the
      patient with ischemic transient attack and one asymptomatic patient, either the
      presence of hearing loss in seven individuals with stroke or dementia.
      CONCLUSIONS: We describe one large family with hereditary cerebrovascular disease
      characterized by recurrent strokes, subcortical dementia, hearing loss, migraine,
      and MRI signal abnormalities typed leukoencephalopathy, subcortical infarcts and
      alterations in corpus callosum. Clinical analysis strongly support the diagnosis
      of CADASIL.

PMID- 11244681
TI  - [Clinical, biomedical , neurological and molecular study of 11 patients with new
      mutations in PAH gene].
AB  - INTRODUCTION: PKU is an autosomal recessive disorder. There is a broad spectrum
      phenotype which depends mainly on residual enzymatic activity and also on other
      factors such as modifying genes and non-genetic factors. This fact makes us
      consider that a multidisciplinary study of these patients is necessary to improve
      knowledge of the condition. OBJECTIVE: To establish phenotype-genotype
      correlation and classify nine new mutations according to severity. PATIENTS AND
      METHODS: We evaluated the clinical data obtained from a multidisciplinary trial
      of 11 patients with PKU/HPA who presented with nine new mutations (P275S,
      P279fsdelC, V388delTG, N61/I62/T63fsdel5bp, P281S, P362T, H1OOR, I164V and Y168H)
      identified during a molecular study of the PAH gene done in Catalonia (Spain).
      RESULTS AND CONCLUSION: In our patients the genotype is correlated with the
      biochemical phenotype whereas the cognitive phenotype depends on determining
      factors such as early diagnosis and diet. Therefore, although PKU may be
      considered to be a complex characteristic, the mutations in the PAH gene are the
      main determining factor of the metabolic phenotype of PKU. A multidisciplinary
      study is the best way to understand and control these patients.

PMID- 11244682
TI  - [Importance of morphostructural changes observed in cortical micro-vessels in
      patients who died after a severe head injury].
AB  - INTRODUCTION: The development of secondary lesions in traumatic head injuries
      seems to be a determinative factor for the survival of these patients.
      Endothelium damage of cortical microvessels could be fundamental in the main
      secondary lesions as cerebral ischemia and intracranial hypertension. OBJECTIVES:
      To investigate which are the main morphological changes that can be observed in
      cortical microvessels from these patients. MATERIAL AND METHODS: We have studied
      15 fresh human brains from subjects died after a severe head injury. The study
      has been carried out by scanning electron microscopy of vascular corrosion casts
      and confocal microscopy of histological sections after immunocytochemistry, as
      well as detection of apoptosis by TUNEL technique. RESULTS AND CONCLUSIONS: The
      most significant structural alterations were observed mainly on arterioles and
      capillaries of the middle and deep vascular zones of the cerebral cortex.
      Corrosion casts showed vessels with longitudinal folds, sunken surface with
      craters and flattened vessels with reduced lumen. Histological sections
      immunostained with MAS-336 also showed vessels with longitudinal folds and
      thinning of their vascular lumen, the presence of cytoplasmic round bodies and a
      thickening of endothelial cell membrane. TUNEL method revealed a positive
      staining of some endothelial cells. The structural alterations observed seem to
      reveal a situation of cellular damage of endothelium in the human cortical
      microvessels from these patients. It can be thought that this kind of lesions, as
      well as the secondary functional injury of the blood brain barrier, could play an
      important role in the development of secondary damage.

PMID- 11244683
TI  - [Comparison of the effects of the administration of fluoxetine and sertraline on
      the immune markers of the mu opioid receptor in the rat brain].
AB  - INTRODUCTION: Chronic fluoxetine or imipramine administration in rats can
      generate a similar increase in the number of neural cells immunostained for mu
      opioid receptors in several prosencephalic regions. OBJECTIVE: The aim of the
      present work was to describe the effects of chronic sertraline administration on
      mu opioid receptor immunostaining in several rat brain prosencephalic regions, in
      order to compare with previously described fluoxetine effects. MATERIALS AND
      METHODS: Experimental animals were chronically administered with sertraline
      (i.p.). An immunocytochemical method, with the aid of a computerized image
      analysis system, was used in order to measure the number of neural cells
      immunostained for mu opioid receptors in several prosencephalic regions. RESULTS:
      Although chronic sertraline administration in rats generates a significant
      increase in the number of neural cells immunostained for mu opioid receptors in
      the caudatus-putamen, dentate gyrus, lateral septum and the frontal, parietal and
      piriform cortices, slight regional differences, with respect to fluoxetine
      action, were found. Thus, a more marked action on parietal cortex and lateral
      septum, and a lesser action on the frontal cortex, were found. CONCLUSION:
      Regional differences in sertraline effects, with respect to fluoxetine, could be
      related to a lesser incidence of psychomotor impairment.

PMID- 11244684
TI  - [Clinical and genetic studies of a family from Peru affected by spinocerebellar
      ataxia type 7].
AB  - INTRODUCTION: Recently the clinical and genetic investigation of cerebellar
      diseases has experienced an extraordinary advance due to localization of the
      disorders in different chromosomal loci. This type of investigation has been done
      in Peru in the last decade, studying a Peruvian family from the Huarochiri
      province. PATIENTS AND METHODS: A Peruvian family of 65 individuals in five
      generations, affected by several neurological disturbances associated with
      ataxia, were studied by clinical, neurological, ophthalmological,
      neuroradiological and genetic methods. The genetic study was done in the
      neurogenetics laboratory of the University of Utah (Salt Lake City, United
      States). RESULTS: The patients showed equilibrium disturbances, gait
      difficulties, ophthalmoplegia, corticospinal signs, cognitive deficiencies,
      visual weakness, maculopathy, retinal degeneration, optic nerve atrophy and
      atrophy of the cerebellum, brain stem and cerebral hemispheres. The DNA in 30
      individuals showed, in the neurologically affected, repeated expansion of CAG
      triplets in the short arm of chromosome 3p. CONCLUSIONS: The findings in this
      family suggests that they suffer from spinocerebellar ataxia type 7. This could
      be the first description of the disease in Latin-America.

PMID- 11244685
TI  - [Chronic tension headache in the neurological outpatient clinics].
AB  - INTRODUCTION: Headache is the commonest cause of neurological consultation in
      Spain. Chronic tension headache is a common reason for consultation, although
      diagnosis is difficult. OBJECTIVES: To emphasize the profile of a patient with
      chronic tension headache and analyze the differences from other groups of
      neurology patients. PATIENTS AND METHODS: We selected chronic tension headaches
      on the criteria of the International Headache Society, in patients who were seen
      for the first time in one of 18 Neurology Clinics of the Communidad Autonoma de
      Aragon during a three month period in 1995. We analysed age, sex, place of
      origin, provisional diagnosis made by the referring doctor, whether the referral
      was correct or had to be reviewed. These variables were compared with groups made
      up of all the patients, the other patients and headaches in general. RESULTS: A
      total of 3,489 patients were seen: 889 had headache (25.5% of the total number of
      patients) and 268 had chronic tension headache (7.6% of all the patients). The
      average age was 47.4 years (SD: +/- 18.7) and 72% were women. Family doctors
      referred 89.5%. The provisional diagnosis was correct in 52.6% and 17% required
      further visits. CONCLUSIONS: Chronic tension headache leads to frequent
      neurological consultation. This was only exceeded by cerebral vascular pathology
      (12%) and migraine (10.5%), making up 29.4% of all headaches. There was a marked
      predominance of women, who were younger than patients with other neurological
      disorders. In spite of the frequency, the family doctors were correct in their
      provisional diagnosis less often than in other neurological conditions. Although
      the condition is chronic, the neurologist acted mainly as a consultant and saw
      few follow-up cases.

PMID- 11244686
TI  - [The relation between carotid ultrasound changes and seropositivity to Chlamydia
      pneumoniae in patients with acute stroke].
AB  - INTRODUCTION: Several infectious agents have been found to be involved in
      atherogenesis over the past decade. Chlamydia pneumoniae is one of the commonest
      associated agents. In this study we have analysed the possible relationship
      between a high level of antibodies to Chlamydia, and the presence of carotid
      ultrasound changes in patients who have had strokes. PATIENTS AND METHODS: We
      studied 230 patients admitted consecutively to the Stroke Unit in our hospital,
      with the diagnosis of stroke. All the patients in the group had carotid duplex
      ultrasound studies to assess the degree of stenosis. All these patients also had
      serological studies using micro-immunofluorescence to detect antibodies to
      Chlamydia pneumoniae. RESULTS: Only 35 patients were found to have positive
      Chlamydia pneumoniae serology. The degree of atheromatosis was similar in the
      patients with high levels of IgG for Chlamydia pneumoniae and in those with
      normal serology. There was no statistically significant relation between the
      degree of stenosis and being seropositive for Chlamydiae. CONCLUSIONS: Our
      findings suggest that in an unselected population of stroke patients there is no
      relations between carotid atheromatosis and positive serology findings to
      Chlamydia pneumoniae. If there is any relationship between Chlamydia pneumoniae
      and carotid atheromatosis, serology does not seem to be a technique which is
      suitable for its assessment.

PMID- 11244687
TI  - [Parkinsonian syndromes in Medellin (Colombia)].
AB  - INTRODUCTION: The definition of parkinsonian syndromes is based on clinical
      criteria. OBJECTIVE: To determine the frequency and management of parkinsonism,
      using criteria of inclusion and exclusion. PATIENTS AND METHODS: We selected 302
      consecutive patients, 147 females and 155 males, with parkinsonism, age 66.8
      (11.4) (range: 13-90), grades of education 7.5 (4.3) (range: 0-20). A structured
      and quantitative protocol was applied to the sample. RESULTS: The most frequent
      parkinsonian syndrome was the defined idiopathic Parkinson's disease with 132
      participants (43.7%). Probably idiopathic Parkinson's disease was found in 60
      cases (19.9%), and possible idiopathic Parkinson's disease in eight cases (2.6%);
      early onset Parkinson's disease in 10 cases (3.3%), juvenile Parkinson's disease
      in one case (0.3%), familial Parkinson's disease in five cases (1.7%); cortical
      Lewy body disease in 16 cases (5.4%), progressive supranuclear palsy in nine
      cases (3.3%), multiple systemic atrophy in eight cases (2.6%). Secondary
      Parkinson's disease was distributed as follow: vascular disease in 24 cases (8%),
      local lesion in 11 cases (3%), medications in 16 cases (5.3%),
      meningoencephalitis in one case (0.3%) and syphilis in one case (0.3%). Without
      medication was found 1.5% of sample, which was in Hoehn & Yarh's state I to II.
      In monotherapy was found 23.2%, with two medications 46.7%, with three 23.5% and
      with four drugs 5.1%. Levodopa was prescript to 70.9%, anticholinergic to 51.3%,
      MAO-B-I to 33.4%, amantadine to 33.1%, D2 stimulants to 18.5%, and COMT-I to
      2.6%. CONCLUSION: Structured protocol for assessment of parkinsonian syndromes
      allows reliable diagnoses for clinical and epidemiological purposes.

PMID- 11244688
TI  - [Unusual bulbar infarct and occlusion of the vertebral artery].
AB  - INTRODUCTION: Isolated bulbar infarcts are infrequent. Because of the vascular
      anatomy the lateral region is the most commonly affected, and in this clinical
      disorder the various signs and symptoms are grouped together as the so-called
      Wallenberg's syndrome. Since the introduction of magnetic resonance (MR) it has
      been possible to correlate the extent and site of the laterobulbar area involved
      with the most probable vascular topography and etiopathogenesis. CLINICAL CASE:
      We describe the case of a 69 year old female patient with all the symptoms of
      Wallenberg's syndrome and two potential causes of stroke (emboliogenic
      cardiopathy and atherothrombotic vascular occlusion), in whom MR showed the
      presence of an isolated bulbar lesion of unusual morphology which had previously
      been described as being of thrombotic origin. CONCLUSIONS: In spite of the small
      area of the brain involved, in laterobulbar infarcts MR permits definition of
      different topographic patterns of ischemic lesions. Some of these patterns have
      been correlated with the specific aetiology of an infarct. Therefore there is
      twice the importance of cerebral MR in cases of suspicion of lateral bulbar
      ischaemia, since it not only assists in diagnosis and its clinicopathological
      correlations, but also, as in our case, helps to have a clinical suspicion of the
      most likely etiopathogenesis of the stroke.

PMID- 11244689
TI  - [Hypertrophic pachymeningitis. A review of the histories of two cases and
      pathological relationship with the Tolosa-Hunt syndrome and the orbital
      pseudotumor].
AB  - INTRODUCTION: Hypertrophic pachymeningitis is an infrequent condition which
      starts with a thickening of the dura mater and whose pathogenesis is unknown. We
      present two new cases of unknown aetiology. CLINICAL CASE: Case 1. A 53 year old
      man complained of occipital headache, tinnitus and deafness since February 1981.
      In October 1981 he was admitted to hospital with a worse headache, perio-orbital
      pain, dysgeusia and ipsilateral peripheral facial palsy. In December he had
      generalized tonic-clonic seizures and paralysis of the VII and XI right cranial
      nerves and IX, X and XII left cranial nerves. In February 1982 he developed right
      trigeminal neuralgia. He was readmitted in November 1983 with continuous
      headache, vomiting and a behavior disorder. On CT there was marked attenuation of
      the posterior dura mater, which the neurosurgical department considered
      unsuitable for biopsy. He died in March 1985. On necropsy there was hypertrophic
      pachymeningitis. Case 2. A 62 year old patient consulted in November 1995
      complaining of right hypoacusia for the past six months, progressively
      accompanied by ipsilateral paralysis of the II, IV, VI, VII and VIII cranial
      nerves but with no other alterations on physical examination. Analytical and
      serological investigations were normal. Cranial MR showed an extraparenchymatous
      infiltrating lesion in the middle cranial fossa. Biopsy was decided on when no
      clinical improvement was seen with corticosteroid treatment. The pathologist
      reported hypertrophic pachymeningitis. Treatment was started with
      cyclophosphamide in monthly doses and the condition has remained stable to date.
      CONCLUSION: With these two cases we wish to establish a pathogenic relation
      between the Tolosa-Hunt syndrome and orbital pseudotumor and show the role played
      by immunosuppressive treatment in the control of hypertrophic pachymeningitis.

PMID- 11244690
TI  - [Schizencephaly associated with porencephaly in a girl with congenital
      cytomegalovirus infection].
AB  - INTRODUCTION: At the present time it is perfectly clear that schizencephaly is an
      anomaly of neuronal migration and porencephaly is the result of destruction of
      the cerebral cortex. Schizencephaly is the final result of a variety of lesions
      which occur during a critical period of the development of the brain. Imaging
      studies have shown many cerebral anomalies varying from lissencephaly to
      multicystic encephalomalacia. We report the case of a girl in whom porencephaly
      was associated with schizencephaly and in whom angioresonance showed hypoplasia
      of the right middle cerebral artery. CLINICAL CASE: The parents of an eight month
      old girl consulted us after observing that she had reduced movement of her left
      arm. On clinical examination there was left hemiparesia. Both CAT and MR showed
      closed lip schizencephaly of the left hemisphere and an area of right
      frontoparietal encephalomalacia. Study of the vascular structures showed
      underdevelopment of the right middle cerebral artery. CONCLUSIONS: The
      cytomegalovirus has been considered to be the principal infectious agent involved
      in the aetiology of different disorders of neuronal migration. It has been
      reported that the cytomegalovirus causes vasculitis which leads to reduction in
      perfusion and lesions due to secondary encephalomalacia. The fact that our
      patient had a hypoplastic middle cerebral artery, and a normal left middle
      cerebral artery, may be explained by subsequent recanalization of the middle
      cerebral artery. This would seem to indicate that the lesion causing
      schizencephaly is older and there has been time for recanalization.

PMID- 11244691
TI  - [Demyelinating pseudotumoral lesion prior to a primary cerebral lymphoma].
AB  - INTRODUCTION: Some case of demyelinating pseudotumoral lesions preceding the
      appearance of primary cerebral lymphoma have been reported. The relation between
      the two conditions is not known. We report the case of a woman in whom a
      demyelinating pseudotumoral lesion had been diagnosed on biopsy and who developed
      a primary cerebral lymphoma 13 months later. CLINICAL CASE: In October 1997 a 38
      year old woman presented with a secondarily generalized focal motor seizure.
      Neuroimaging showed a left frontal tumour with marked oedema and uptake of
      contrast medium. Based on the clinicoradiological suspicion of a primary cerebral
      tumour or metastasis, treatment was started with dexamethasone. Approximately two
      weeks later a stereotaxic biopsy was done, in which there was demyelination with
      conservation of the axons and perivascular inflammatory infiltration with
      polyclonal T and B lymphocytes. The diagnosis was 'a pseudotumoral form of a
      demyelinating disease'. Thirteen months later the patient had episodes of falling
      to the floor, followed by subsequent slight confusion and difficulty in speaking.
      On neuroimaging studies (cerebral CAT and MR) there was a tumour of the left
      basal ganglia, considerable oedema and homogeneous marking following the
      injection of contrast. Anatomopathological study of the lesion showed a B cell
      lymphoma. CONCLUSION: In cases of pseudotumoral demyelinating lesions the
      possibility of a primary cerebral lymphoma of the central nervous system must be
      remembered.

PMID- 11244692
TI  - [Specific treatment of the acute cerebral infarct. Present and future].
AB  - INTRODUCTION: Specific pharmacological strategies in the treatment of the acute
      phase of a cerebral infarct are directed towards potentiating reperfusion
      (antithrombotic or thrombolytic drugs) and neuroprotection as early on as
      possible. DEVELOPMENT: The antithrombotic agents are anticoagulants,
      hypofibrinogemiant agents (Ancrod) and antiaggregants. The IST was done with
      anticoagulants, using heparin subcutaneously which causes increased bleeding
      without any obvious benefit. Others have used heparinoids (TOAST) or low
      molecular weight heparins (FISS or FISS bis) with no benefit either but with
      excessive bleeding with the former. Regarding Ancrod, a recent North American
      study (STAT) with administration of it within three hours showed significant
      benefit three months later. Another European study is still underway (ESTAT).
      With regard to antiaggregants, IST and CAST were done using Aspirin, showing a
      drop in early recurrences and increase in recoveries, so that aspirin has been
      recommended for use during the first 48 hours. There are studies using abciximab
      (Reopro), a blocker of the IIb-IIIa glycoprotein receptors, in which phase II
      data have shown that it is safe and tends to improve the outcome. A study on
      phase III is currently ongoing. The thrombolytic drugs have been evaluated in
      various trials. The PROACT study evaluated intraarterial pro-UK and showed
      significant recanalization of middle cerebral artery occlusions, but with a
      larger number of hemorrhages and no reduction in mortality and besides, in PROACT
      II the outcome of treated patients was better. The NINDS trial using intravenous
      rt-PA (0.9 mg/kg in < 3 hours) showed an improved functional state 3 months
      later. In the ECASS doses of 1.1 mg/kg of rt-PA in < 6 hours were used and
      improvement was seen after three months which was countered by an increase in
      cerebral hemorrhage and mortality. The ECASS II, with similar dosage to NINDS and
      an identical window to ECASS, showed a favorable tendency in the evolution of the
      treated group, with no increase in symptomatic intracranial hemorrhages.
      Neuroprotectors have shown to be effective in experimental models of ischaemia
      but at the moment there is no definite evidence of their benefit in the numerous
      trials carried out on humans, although some subgroups of patients seem to benefit
      from some of them. Studies therefore are still being done. In future their use in
      combination with thrombolysis may be considered.

PMID- 11244693
TI  - [Introduction to functional magnetic resonance].
AB  - INTRODUCTION: During recent years we have seen the birth and development of a
      technique destined to revolutionize the world of the neurosciences, functional
      magnetic resonance (fMR). This new technique presents many challenges, both from
      the hardware point of view (little signal, relatively limited spatial and
      temporal resolution, artefacts, etc.) and of analysis (correction for movement,
      improved signal/noise ratio, statistical models used, etc.). DEVELOPMENT: In this
      paper we review the most important aspects of fMR regarding artefacts, analysis
      and origin of the signal, based on the widely used BOLD contrast. CONCLUSION:
      Although still at its beginnings, and in spite of aspects which need improvement,
      fMR appears to be a very useful tool both for clinical applications and
      investigation, and its use should be encouraged by normal MR imaging teams in
      everyday clinical practice.

PMID- 11244695
TI  - [Erosion of the spinal canal due to dural ectasia in a patient with ankylosing
      spondylitis].

PMID- 11244694
TI  - [Dynamics of intrathecal immunoglobulin synthesis].
AB  - INTRODUCTION: Dynamics of the immune response in Central Nervous System (CSN) is
      different from the well-known switch of IgM synthesis to IgG synthesis in blood.
      OBJECTIVE: Broadcast the behavior and the factors involved in the dynamics of the
      intrathecal immune response in infectious neurological disorders. DEVELOPMENT:
      The lack of a switch from IgM class response to IgG response could be more
      related to regulation-modulation mechanisms of the CNS immune response than
      differs from blood in a different cytokines composition, and the possibility of
      chemokines synthesis during the neuroinflammatory process, and the neuroimmune
      endocrine mechanisms. The immune pattern can be stable like neuroborreliosis, and
      can be modify like in herpes simplex meningoencephalitis. It could have a typical
      pattern like in Neisseria meningitidis meningoencephalitis and neurotuberculosis.
      Also the pattern could be still detectable for many years after sufficient
      treatment and complete recovery of the symptom-free patients like in
      neurosyphilis or an advanced precocious response during the childhood. In HIV
      encephalopathy the pattern remains the same during the evolution but in other
      virus infections, like Echo 6 or Coxsackie B5, depends on the biological agent.
      CONCLUSIONS: In order to know the acuity of the disease, we have to know the
      physiopathologic characteristics of the biological agents, time courses,
      locations of the pathological processes, and the host age. The main signs in
      cerebrospinal fluid of an acute, active disease of CNS are the increased of
      cerebrospinal fluid cell count and the increased of albumin ratio.

PMID- 11244696
TI  - [Bilateral striatal necrosis following a wasp sting].

PMID- 11244697
TI  - [Generalized idiopathic torsion dystonia (DYT1) in two brothers].

PMID- 11244698
TI  - [Urinary retention as the first sign of rhombencephalitis due to Listeria
      monocytogenes].

PMID- 11244699
TI  - [A new challenge: renoprotection].

PMID- 11244700
TI  - [Drug dependence and addictions in the anesthesiology setting: breaking the
      silence].

PMID- 11244701
TI  - [Postoperative pain and surgical treatment of trapeziometacarpal osteoarthritis
      of the thumb after ambulatory surgery].
AB  - OBJECTIVE: The course of pain and the incidence of the side effects from
      analgesics were evaluated for 15 days in 26 consecutive outpatients who underwent
      a surgical cure of trapeziometacarpal osteoarthritis of the thumb under regional
      block. STUDY DESIGN: Prospective study. METHODS: The analgesic regimen prescribed
      at discharge consisted on a regular administration of a combination of ketoprofen
      (50 mg.6.h-1) plus the association of acetaminophen and propoxyphene (two
      tablets.6.h-1). Patients were asked to evaluate their pain using a numerical
      rating scale graduated from 0 to 10. Data were collected during a telephone
      interview at day 4, 8 and 15. RESULTS: Overall, patients scrupulously followed
      the medical prescription. At day four, 80% of patients still needed analgesics.
      The mean period during which NSAID, acetaminophen and propoxyphene were
      maintained was 4 and 6 days respectively. Fifty percent of patients reported
      severe pain during postoperative day 1 and 2. Moderate pain was reported at day 3
      and 4 in respectively 54% and 42% of cases. Beyond this period, most patients
      indicated pain of weak intensity (71% at day 8). Epigastric pain has been noticed
      for 27% of patients. CONCLUSION: The surgical correction of trapeziometacarpal
      osteoarthritis of the thumb is frequently performed according to an ambulatory
      setting. The fact that 50% of patients reported severe pain during the early
      postoperative period emphasize the inadequacy of our postoperative pain
      management for this surgical procedure.

PMID- 11244702
TI  - [Effectiveness of low mivacurium if its injection is postponed by a non-invasive
      pressure determination on the homolateral arm].
AB  - OBJECTIVE: We assessed the neuromuscular characteristics of 0.2 mg.kg-1 of
      mivacurium while its injection was concomitant to a non invasive blood pressure
      measurement in the ipsilateral arm. PATIENTS: Thirty-one patients ASA I-II were
      randomized into two groups. Group cuff (n = 15) and Group control (n = 16).
      METHODS: General anaesthesia was induced with fentanyl, thiopentone and
      mivacurium in all patients, however in the cuff group, measurement of non
      invasive blood pressure was performed immediately after the injection of
      mivacurium. Comparison was made on neuromuscular blockade of the adductor
      pollicis (AP) by mechanomyography, and intubating conditions which were guided by
      the visual estimation of the orbicularis oculi's (OO) response. RESULTS: In the
      cuff group, six out of 15 patients did not have complete blockade at the OO
      against one out of 16 in the control group, (Fisher exact test p < 0.05).
      Intubation time was significantly delayed in the cuff group, 201 +/- 66 s versus
      123 +/- 32 s in the control group, (t test p < 0.001). The maximum neuromuscular
      blocking effect at the AP was significantly greater in the control group 99 +/-
      2% against 89 +/- 7% in the cuff group, (t test p < 0.01). The onset of maximum
      blockade at the AP was longer in the cuff group 294 +/- 40 s versus 179 +/- 92 s,
      (t test p < 0.001] in the control group. Time to 25% recovery was shorter in the
      cuff group 16 +/- 3 min versus 20 +/- 5 min, in the control group (t test p <
      0.05). CONCLUSION: This study suggests that non invasive blood pressure
      measurement of the ipsilateral arm, concomitant to the injection of mivacurium
      decreases the potency of mivacurium. This finding is mostly explained by the
      early hydrolysis of mivacurium in the plasma of the excluded arm.

PMID- 11244703
TI  - [Is the direct admission to the recovery service or to the intensive care unit of
      patients cared for by the Smur system justified?].
AB  - STUDY DESIGN: The French system of Samu-Smur allows the admission of patients
      directly in intensive care unit (ICU). The aim of this study is to examine the
      utility of the Samu-Smur with regard to such direct admission (DA). PATIENTS AND
      METHODS: This retrospective study was performed by the Samu of Paris. Patient
      details were gathered from three reports: namely hospitalization, transport and
      regulation reports. These were analysed to decide whether the admission
      diagnostic was exact, whether the patient's condition was serious, whether the
      prehospital treatment justified direct admission into an ICU and whether the
      management was coherent. RESULTS: In 1997, 409 (31%) cases were studied among the
      1,350 admitted patients in ICU. Three groups of patients were classified
      according to admission to surgical (n = 54), medical (n = 180), cardiological ICU
      (n = 175). The prehospital diagnosis was confirmed by the hospitalization report
      in 91% of patients in the all three groups. The patient's condition was found to
      the serious in all cases. Justification of the treatment was respectively found
      in 96, 88 and 84% of patients. The coherence of management was confirmed in 94,
      96 and 89%. DISCUSSION: This study has shown that Samu-Smur management lead to
      justified DA in ICU for all patients in the study. Prospective studies are needed
      to show the advantages of this strategy in term of speed of management and
      outcome.

PMID- 11244704
TI  - [The use of propofol does not increase the cost of the management of patients in
      heart surgery with extracorporeal circulation].
AB  - OBJECTIVES: Evaluation of the cost of propofol used for fast-track in cardiac
      surgery and its impact on global cost of management for anaesthesia and intensive
      care. STUDY DESIGN: Case-control study, prospective (1998) and retrospective
      (1994). PATIENTS: Twenty patients operated for cardiac surgery in 1998 and
      scheduled for fast-track anaesthesia. Twenty patients in 1994 matched for
      different criteria to the patient of 1998. METHODS: In 1998, all drugs, materials
      used and X-rays, biochemical assays performed were prospectively collected and
      their cost calculated. In 1994, similar calculations were done retrospectively.
      Comparison of duration of mechanical ventilation, hospitalization in intensive
      care and in the hospital were performed. RESULTS: Cost of anaesthesia was similar
      in 1994 and 1998 (2,646 FF versus 2,294 FF). Global cost of management was
      significantly lower in 1998 in comparison to 1994 (5,439 FF versus 8,558 FF).
      Duration of mechanical ventilation, hospitalization in intensive care and in the
      hospital were shorter in 1998 than in 1994. CONCLUSION: Despite a higher cost of
      propofol for anaesthesia and postoperative sedation in comparison to midazolam,
      the global cost of management decreased significantly in relation to a one day
      decrease in hospitalization in the intensive care unit.

PMID- 11244706
TI  - [Non-steroidal anti-inflammatory agents and diuretics: a combination with
      nephrotoxic risks].
AB  - We report the case of a reversible postoperative acute renal failure in a 55-year
      old woman without preoperative risk factors who underwent a retinal surgery. The
      association of diuretics with nonsteroidal antiinflammatory drugs was probably
      responsible of an ischaemic acute tubular necrosis. Vitreoretinal surgery's
      postoperative period might be associated with a specific risk for the kidney
      because of an usual intensive diuretic prescription. Nonsteroidal
      antiinflammatory drugs should be avoided if possible in this indication.

PMID- 11244705
TI  - [Risk of drug dependence for anesthesiologists].
AB  - OBJECTIVE: No epidemiologic study or any other type of evaluation has been
      performed so far concerning substance abuse among french anaesthetists. We
      therefore reviewed the English literature to analyse relevant data on this topic.
      DATA SOURCES: A search for edited manuscripts dedicated to drug addiction in
      anaesthetists was conducted on Medline and Databases (Toxibase and ASA websites).
      STUDY SELECTION: Forty-two references related to this problem were selected
      noteworthy based on epidemiologic data provided. SYNTHESIS: 1% to 2% of
      anaesthetists are considered drug addicts in epidemiological studies. Whether the
      prevalence of drug addiction is higher in anaesthetists compared to other medical
      specialists remains controversial. Mortality in addict anaesthetists is more than
      15% over 5 years. Rehabilitation programs succeed in 60% to 80% of the cases but
      residents in anaesthesia need to be redirected to another medical specialty.

PMID- 11244707
TI  - [Pulmonary hematoma: unusual complication of central catheterization].
AB  - We report a case of intrapulmonary haematoma complicating a subclavian vein
      catheterization, in a 52-year-old patient treated with anticoagulants. The
      pathophysiology, the prevention and the treatment of this complication are
      discussed.

PMID- 11244708
TI  - [Digestive hemorrhage originated elsewhere].
AB  - We report the case of splenic subcapsular haematoma, that happens to a woman
      after three months. Breaking and fistulation of the splenic haematoma into the
      gastric cavity and its subsequent evacuation made it first identify as digestive
      haemorrhage.

PMID- 11244709
TI  - [Calcification of thrombus associated with central venous catheter: unusual
      complication].
AB  - Thrombosis originating from the tip of central venous catheter is a well known
      complication. The calcification of such a thrombus is very rare. Until now, only
      two cases had been described with long-term indwelling central venous catheters
      used for total parenteral nutrition. We report the first case of a calcified
      thrombus occurred during a short-term central venous catheterisation. The
      presumptive mechanism of thrombus calcification is precipitation of calcium salts
      and its deposition on a pre-existent thrombus. In total parenteral nutrition the
      mechanism of calcification seems to be multifactorial. Thus, the precipitation of
      calcium phosphate is increased by the following factors: higher calcium and
      phosphate concentrations, the use of calcium chloride instead of calcium
      gluconate, lower pH solutions, slow infusion rate.

PMID- 11244710
TI  - [Acute poisoning with phenytoin caused by an error in the administration of
      fosphenytoin (Prodilantin)].
AB  - Following surgery for a chronic subdural haematoma, a 74-year-old patient
      received fosphenytoin as prophylaxis for epilepsy. The patient received 10 times
      the prescribed dose. This error in the administration of fosphenytoine was
      facilitated by a confusing labeling of the product. The phenytoin blood level was
      79 micrograms.mL-1. The main adverse effect was a coma requiring 5 days of
      mechanical ventilation. No adverse cardiovascular event was noted. The phenytoin
      blood levels returned toward the therapeutic range in 8 days. At discharge from
      the hospital 20 days after surgery, the patient did not have any sequela from the
      fosphenytoin intoxication.

PMID- 11244711
TI  - [Very severe anaphylactic shock after anesthesia induction].

PMID- 11244712
TI  - [Conjunctivitis associated with the inadequate use of Bodedex while
      decontaminating a facial mask].

PMID- 11244713
TI  - [Intravenous injection: beware of the superficial cubital artery!].

PMID- 11244715
TI  - [Inter-sternocleidomastoid block and diaphragmatic paresis].

PMID- 11244714
TI  - [Use of remifentanil in conscious sedation].

PMID- 11244716
TI  - [Beta-catenin: its discovery as a cadherin-associated protein and its function as
      a transcription activator].

PMID- 11244717
TI  - [A novel picture of protein from high pressure NMR].

PMID- 11244718
TI  - [Structure of calcium-activated photoprotein aequorin].

PMID- 11244720
TI  - [Structure and function of the CAD domains of caspase-activated DNase(CAD) and
      inhibitor of CAD].

PMID- 11244719
TI  - [A novel function of the tumor suppressor APC].

PMID- 11244721
TI  - [Cryptogram embedded in mitochondrial presequences].

PMID- 11244722
TI  - [The efficient methods for gene disruption in fungi].

PMID- 11244723
TI  - [Thoracoscopic pleural biopsy under local anesthesia using a 2 mm laparoscope].
AB  - Thoracoscopy is indicated in patients with undiagnosed effusion after
      conventional methods. It has been usually performed under general anesthesia or
      using a thoracoscope with a thoracoscope with a diameter over 5 mm. However, it
      is an invasive diagnostic technique. We evaluated the feasibility of
      thoracoscopic pleural biopsy under local anesthesia using a 2 mm laparoscope. Six
      patients with a pleural effusion of unknown etiology after conventional methods,
      underwent thoracoscopy under local anesthesia. A 2 mm laparoscope and biopsy
      forceps (2 mm Minisite, United States Surgical Corp., USA) was used in all
      patients. Pleural fluid was removed, and the thoracic cavity was inspected.
      Thoracoscopic intercostal blocks were performed with 1% lidocaine, and then a
      biopsy was performed. The biopsy specimen was sent for histopathology. Three
      patients were shown to have carcinomatous pleurisy, two of them with localized
      lesions less than 10 mm. In the remaining three patients, non-specific diagnoses
      were made, but long-term follow-up revealed no malignant pleural disease.
      Although the pictures obtained using a 2 mm laparoscope were inferior in quality,
      they were adequate for the detection of malignant lesions in the pleural cavity.
      There were no procedure-related complications. These findings suggest that
      thoracoscopy using a 2 mm laparoscope is (1) a useful diagnostic tool in cases of
      pleural malignancy; (2) a minimally invasive method with the advantage of being
      easily performed under local anesthesia. Thus, thoracoscopic pleural biopsy using
      a 2 mm laparoscope appears to be useful for undiagnosed pleural effusion.

PMID- 11244724
TI  - [Therapeutic efficacy of amantadine hydrochloride in patients with epidemic
      influenza A virus infection].
AB  - A virus infection was studied using half of the normal oral dose of amantadine
      hydrochloride-100 mg/d instead of 200 mg/d. The patients in this study, who
      visited the clinics during January and February 1999, were confirmed within 48
      hours to have influenza A virus infections by the Directigen FluA test. Using a
      quasi-randomized controlled trial, 26 patients were treated with amantadine
      hydrochloride in addition to the usual medication, while 23 were treated with
      only the ordinary medication. There were no significant differences in the mean
      age, 35.6 years old, or in clinical features between the two groups. The period
      of fever over 38 degrees C in the amantadine treated group was 1 day while that
      in the control group was 1.7 days, which shows a significant difference (p =
      0.049). There was no significant difference in the duration of aching, such as
      arthralgia, or of general fatigue. There was no significant difference in the
      appearance of subsequent new symptoms after the onset of influenza A virus
      infection. In conclusion, it is expected that oral amantadine hydrochloride, 100
      mg/d, together with the ordinary medication, will reduce the duration of the
      period of fever over 38 degrees C.

PMID- 11244725
TI  - [Study on pulmonary cryptococcosis disclosed by chest radiographic screening in
      Nagasaki Prefecture].
AB  - We conducted a retrospective investigation of 20 cases of pulmonary
      cryptococcosis discovered by chest radiographic screening in Nagasaki Prefecture
      among 2,011,577 persons over a period of 9 years, Apr. 1989-Mar. 1998. Eight
      males and 12 females between 15 and 72 years of age(mean: 46.6 years) were
      diagnosed as having pulmonary cryptococcosis. The mean detectability of pulmonary
      cryptococcosis by screening was 0.99 per 10(5) persons: 1.30 for residents, 0.51
      for school children and 0.80 for workers. Chest radiography showed shadows of
      solitary nodules in 9 patients, multiple nodules in 4, infiltration in 4 and
      others in 3. Cavities were noted in 7. However, it was difficult to distinguish
      between pulmonary cryptococcosis from pulmonary tuberculosis and pulmonary cancer
      based on radiographic data alone. Final diagnoses for 11 and 3 patients,
      respectively, were made using TBLB or BAL, and lung biopsy. Sixteen patients each
      underwent an Eiken-Latex agglutination test (serum cryptococcus antigen test) and
      15 (93.8%) had positive results. The serum antigen level thus appears to be a
      useful indicator in the supplementary serological diagnosis of pulmonary
      cryptococcosis.

PMID- 11244726
TI  - [A case of chronic hypersensitivity pneumonitis induced by shiitake mushroom
      spores].
AB  - A 73-year-old woman was admitted to our hospital with a low-grade fever, dry
      cough and dyspnea on exertion as the chief complaints. She had been a
      professional shiitake mushroom grower for 50 years. Three years before visiting
      our hospital, she had been suspected of having hypersensitivity pneumonitis as a
      result of chest X-ray examination, bronchoalveolar lavage and transbronchial lung
      biopsy performed at another clinic. No antigens were identified at that time, but
      prednisolone was administered. On admission to our hospital, chest radiography
      and chest computed tomography revealed an interstitial shadow with subpleural
      honey-combing in both lower lung fields. After steroid pulse therapy, dyspnea on
      exertion and hypoxia improved moderately. Because of recurrence of the dyspnea,
      however, she was admitted on four separate occasions. On the second admission, an
      increase in lymphocytes was found by bronchoalveolar lavage, and septal
      lymphocytic infiltration accompanying fibrosis was demonstrated by transbronchial
      lung biopsy. On the fourth admission, a detailed immunological examination and an
      environmental survey were performed. The environmental provocation test yielded
      clinical symptoms similar to those experienced at the mushroom farm. Furthermore,
      tests of precipitation and lymphocyte proliferation in response to shiitake
      mushroom extracts were positive. Finally a diagnosis of chronic hypersensitivity
      pneumonitis induced by shiitake mushrooms was confirmed.

PMID- 11244727
TI  - [Improvement of a case of broncholithiasis after spontaneous lithoptysis].
AB  - A 53-year-old woman was admitted for recurrent hemoptysis and cough. The chest
      radiograph showed an infiltrative shadow in the left upper region. Chest tomogram
      and CT scan showed a small calcification and consolidation in the left upper
      lobe. Fiberoptic bronchoscopy revealed fresh hemorrhage from the left upper
      bronchus but no broncholith or bleeding point were detected. Since the symptoms
      had disappeared by 10 days after admission, the patient was discharged and
      followed up as an outpatient. Three weeks later, she spontaneously expectorated a
      stone 3 mm in maximum diameter, with an irregular surface. Analysis revealed that
      the stone's composition was 56% of calcium phosphate and 44% of calcium
      carbonate. Hemoptysis seemed to have been caused by the broncholith, which had
      originated as a calcification of a peribronchial lymph node that subsequently
      eroded its way into the airway. After lithoptysis, no recurrence has been
      observed.

PMID- 11244728
TI  - [Sjogren's syndrome with multiple bullae and pulmonary nodular amyloidosis].
AB  - We report a case of Sjogren's syndrome with pulmonary involvement diagnosed by
      open lung biopsy. The patient was a 62-year-old woman with antiphospholipid
      antibody syndrome. Her chest radiograph and CT scan showed multiple bullae
      diffusely scattered throughout the lung. The open lung biopsy specimens revealed
      marked inflammatory mononuclear cell infiltration and nodular amyloid deposits in
      the bronchiolar walls. The mechanism of bulla formation appeared to be the check
      valve mechanism caused by the narrowing of the airway by the bronchiolitis. The
      patient was treated with oral corticosteroids, and her symptoms and laboratory
      findings became stable.

PMID- 11244729
TI  - [Familial summer-type hypersensitivity pneumonitis in a grandfather and his two
      and-a-half-year-old grandson].
AB  - We encountered a family in which two of the six members, the grandfather and his
      grandson, had summer-type hypersensitivity pneumonitis in late summer. Chest
      computed tomography of these patients showed small, diffuse nodular shadows in
      both lung fields, with mosaic-like opacities in the grandfather and ground glass
      opacity of both lung fields in the grandson. Bronchoalveolar lavage fluid from
      the grandfather disclosed high total cell counts, high percentages of
      lymphocytes, and a low ratio of CD 4+ cells to CD 8+ cells. Transbronchial lung
      biopsy specimens obtained from the same patient revealed alveolitis with non
      caseous epithelioid cell granulomas in the interstitium and Masson bodies in the
      alveolar septa. These two patients recovered spontaneously after hospital
      admission. They had positive results in provocation tests for their home and were
      positive for serum anti-Trichosporon cutaneum (T. asahii, T. mucoides)
      antibodies. Both cases were accordingly diagnosed as summer-type hypersensitivity
      pneumonitis.

PMID- 11244730
TI  - [A case of paragonimiasis westermani with a high level of interleukin 5 in
      bronchoalveolar lavage fluid].
AB  - A 49-year-old man was admitted to our hospital with a productive cough and bloody
      sputum. Peripheral blood eosinophil counts and serum IgE values were elevated.
      Chest radiography and chest computed tomography revealed a solitary nodule with
      cavitation and satellite lesions in the right middle lobe, in contact with the
      pleura. The diagnosis of paragonimiasis westermani was confirmed by detection of
      ova in the sputum and bronchoalveolar lavage fluid (BALF) samples, and by
      immunoserological examination. The patient was treated with praziquantel for 3
      days at a daily dosage of 75 mg/kg. After treatment, his clinical symptoms and
      radiological abnormalities disappeared. The IL-5 level was high in BALF, but it
      was undetectable in the plasma, suggesting that IL-5 in inflammatory lesions may
      be particularly important in mediating eosinophilia in the blood and BALF in
      paragonimiasis westermani.

PMID- 11244731
TI  - [A case of mumps pneumonia complicated with acute respiratory failure].
AB  - A 38-year-old male with swollen parotid glands was admitted to our hospital with
      dyspnea on effort. Positive serum IgM antibody for mumps supported a diagnosis of
      mumps. Computed tomography (CT) scan showed a ground-glass appearance in both
      lower lungs. On the third day of hospitalization, bronchoalveolar lavage
      demonstrated an elevation of both the total cell (2.0 x 10(6)/cc) and the
      lymphocyte count (83%), as well as a decrease of the CD 4+/CD 8+ ratio (0.4).
      Bronchial biopsy specimens revealed infiltration of lymphocytes in both the
      bronchiolar walls and the alveolar septa. These data were suggestive of mumps
      pneumonia. The patients suffered acute respiratory failure on the seventh day of
      hospitalization, which improved after 3 days of high-dose methyl prednisolone
      therapy. This is the first report of adult mumps pneumonia in Japan. As a result
      of the examination of the bronchoalveolar lavage and a bronchial biopsy of viral
      pneumonia which had been reported in the past, mumps pneumonia was a
      corresponding opinion to other viral pneumonia.

PMID- 11244732
TI  - [A case of limited Wegener granulomatosis with hypereosinophilia].
AB  - A 51-year-old female was admitted to Nagano Matsushiro General Hospital because
      of fever, cough and dyspnea on exertion. Her laboratory data revealed
      leukocytosis with hypereosinophilia, a high erythrocyte sedimentation rate and c
      reactive protein. Chest radiography revealed an infiltration shadow with a cavity
      in the right upper lobe. A lung abscess was diagnosed and antibiotics were
      administered. Laboratory results showed improvement, but chest radiography
      continued to show cavities. She was admitted to our hospital because of fever,
      left pleural effusion and progression of cavities on chest radiographs. She
      showed no abnormalities of the upper airway or kidney, and was negative for c
      antineutrophil cytoplasmic antibody (c-ANCA). Because a positive c-ANCA was seen
      on day 8 of hospitalization, L-type limited Wegener granulomatosis (WG) was
      diagnosed according to Gross et al. Prednisolone (PSL) was administered, which
      improved the anemia, eosinophilia and the cavities. On day 7 of PSL
      administration, of the left pneumothorax occurred as a complication caused by
      perforation of the left chest cavity, but her clinical course was good after a
      cavernectomy was performed. Some studies have reported that limited WG shows a
      negative c-ANCA, and that antibiotic therapy improves inflammation. The L-type of
      limited WG revealed a low-grade positive ratio and titer of c-ANCA. Moreover, L
      type limited WG responds well to therapy. We therefore selected PSL
      administration only against L-type limited WG. We have reported L-type limited WG
      with eosinophilia and the negative effects of c-ANCA at an early clinical stage.

PMID- 11244733
TI  - [A case of non-small-cell lung cancer with intramedullary spinal cord metastasis
      diagnosed pre-mortem].
AB  - The patient was a 54-year-old man who in May 1999 received a diagnosis of
      squamous cell carcinoma, T4 N2 M1, stage IV. Systemic chemotherapy and
      stereotactic radiosurgery were performed only to result in further progression of
      the disease. In August 1999, he experienced gait disturbance due to lumbar pain.
      Rehabilitation improved the gait disturbance and he was discharged. In October,
      since the pain reappeared and there was numbness in the right leg, he was
      readmitted. Brain MRI revealed multiple brain metastasis and whole brain
      irradiation was performed. But his symptoms deteriorated, and palsy of the right
      leg ensued. Later, bladder dysfunction also developed. Since spinal cord MRI
      revealed intramedullary metastasis at Th 12 and L1 levels, we performed
      radiotherapy for the lumbar medullary lesion, together with systemic
      chemotherapy. After chemoradiotherapy the tumor size decreased and the pain
      improved. Cases of lung cancer with intramedullary metastasis are rare,
      especially those diagnosed before death.

PMID- 11244734
TI  - [A case of acute eosinophilic pneumonia induced by inhalation of acetylene].
AB  - A 17-year-old high school student, while carrying out soldering one morning,
      inhaled 100% acetylene, and experienced nausea and bilateral lower limb numbness
      several hours later. In the evening his symptoms worsened, dyspnea followed, and
      the patient was referred to our hospital the next day. On admission chest
      radiography and CT scanning revealed peripheral ground-glass opacity, patchy
      infiltrate and Kerley's B line in the right lung fields, and bilateral pleural
      effusion. Since the laboratory findings revealed leukocytosis without
      eosinophilia, increased CRP, and hypoxemia, bronchoalveolar lavage (BAL) and
      transbronchial biopsy (TBLB) was subsequently performed. Fluid analysis revealed
      marked increases in the total cell and eosinophil counts, and the biopsy result
      showed eosinophilic and lymphocytic infiltration of the alveolar septa. As a
      result, the case was diagnosed as acute eosinophilic pneumonia (AEP). Although
      inhalation of acetylene is known to induce pulmonary edema, all the typical
      findings of AEP but pulmonary edema were seen. This case demonstrates that AEP
      may be induced by inhalation of acetylene.

PMID- 11244735
TI  - [Three cases of primary acute pulmonary cavitation in sarcoidosis].
AB  - Sarcoidosis has a variety of pulmonary manifestations including the nodular, or
      infiltrative form. However, primary cavitary formation is rare. In this report,
      we describe three cases of sarcoidosis with primary acute pulmonary cavitations.
      All three patients were young adults (2 men and 1 woman) and chest radiography
      and chest CT showed bilateral Hilary lymphadenopathy, multiple cavitations with
      thin, smooth walls, and diffuse granular shadows. Primary acute pulmonary
      cavitation of sarcoidosis was diagnosed, since a transbronchial biopsy specimen
      revealed sarcoid granuloma, and there was no evidence of infection, emphysematous
      change, or fibrotic or cystic bronchiectatic changes on chest radiography in any
      case. Corticosteroid therapy was given in all cases for severe extrathoracic
      disease (2 of severe uveitis and 1 of CNS involvement). After the treatment, the
      multiple cavities and diffuse granular shadows in the lung fields disappeared. We
      accordingly suggest that corticosteroid therapy is effective for primary acute
      cavitation in sarcoidosis.

PMID- 11244736
TI  - [Pulmonary thromboendarterectomy for chronic pulmonary thromboembolism in three
      patients with systemic lupus erythematosus and antiphospholipid syndrome].
AB  - Pulmonary hypertension (PH) is a serious and often fatal complication of systemic
      lupus erythematosus (SLE). Several potential mechanisms have been postulated for
      narrowing of vessels as a result of pulmonary vasculitis and pulmonary
      thromboembolism caused by antiphospholipid antibodies. Pulmonary
      thromboendarterectomy for chronic pulmonary thromboembolism is performed to
      alleviate pulmonary hypertension. We report three rare cases of SLE with
      antiphospholipid syndrome in patients who presented with PH secondary to chronic
      pulmonary thromboembolism. Pulmonary thromboendarterectomy was performed, and all
      patients remained well without deterioration of PH after surgery. Pulmonary
      thromboendarterectomy should be considered as an effective method of treatment
      for this disease.

PMID- 11244737
TI  - [Molecular mechanism regulating activation of hepatocyte growth factor].

PMID- 11244738
TI  - [Autocrine regulation of angiogenesis].

PMID- 11244739
TI  - [Pol I class DNA polymerases--structures, functions and base selection
      mechanisms].

PMID- 11244740
TI  - [Analyses of Gli genes functions using mutant mice].

PMID- 11244742
TI  - [Folding elements: an essential unit of foldability revealed by systematic
      circular permutation analysis].

PMID- 11244741
TI  - [Finding partner for orexigenic peptide--the receptor for melanin-concentrating
      hormone (MCH) is a G protein-coupled receptor].

PMID- 11244743
TI  - [Ryanodine receptors and intracellular Ca2+ stores].

PMID- 11244744
TI  - [Stress prevention and supervisor training].
AB  - This article surveys available literature addressing the role of supervisors
      (corporate administrators) in stress prevention activities within the workplace
      and describes some desirable training courses. In most successful stress
      management programs or programs that promote mental health, the provision of
      training for supervisors has been an important strategy. Several reports have
      asserted that proper training is an effective method of reducing worksite stress
      and improving job satisfaction in workers, but few prospective intervention
      studies investigating the truth of these reports have been made. Additional
      research is necessary to assess the validity of various training programs. The
      structure of organizations and employment systems has recently begun to change,
      and the traditional employee-supervisor relationship is slowly disappearing in
      some enterprises, so that the role of supervisors with regard to stress
      management may need to be revised.

PMID- 11244745
TI  - [Surgery for thoracic aortic aneurysms involving the distal arch through a left
      thoracotomy].
AB  - Surgical outcome for thoracic aortic aneurysms involving the distal arch via a
      left thoracotomy using retrograde cerebral perfusion combined with profound
      hypothermic circulatory arrest was reviewed. Twelve patients with a
      atherosclerotic aortic aneurysm between 1994 and 1997 were involved. A proximal
      aortic anastomosis was made by means of an open aortic technique. For the first
      four patients, oxygenated arterial blood from cardiopulmonary bypass was perfused
      retrogradely through a venous cannula positioned into the right atrium. In the
      last eight cases, venous blood provided by a low-flow perfusion of the lower half
      body via the femoral artery, which was still oxygen-saturated, was circulated
      passively in the brain in a retrograde fashion with the descending aorta clamped.
      Prosthetic replacement was done between the distal arch and the proximal
      descending aorta in 6 patients and from the distal arch to the entire descending
      thoracic aorta in 6 patients. The median duration of hypothermic circulatory
      arrest and continuous retrograde cerebral perfusion was 36 minutes and 33 minutes
      respectively. The overall outcome was satisfactory without early mortality--all
      patients survived, although an octogenarian died of respiratory failure 1 year
      postoperatively. Another octogenarian with a ruptured aneurysm developed delay of
      meaningful consciousness, and other two patients with a severely atherosclerotic
      aneurysm suffered permanent neurological dysfunction (stroke) presumably due to
      an embolic episode. The safe and simple combination of profound hypothermic
      circulatory arrest, retrograde cerebral perfusion, and open aortic anastomosis
      protects the brain adequately and produces satisfactory results in surgery for
      aortic aneurysms involving the distal arch through a left thoracotomy.

PMID- 11244746
TI  - [Experience of four cases of postoperative pulmonary embolism requiring surgical
      treatment].
AB  - Four patients underwent a pulmonary embolectomy using cardiopulmonary bypass for
      acute pulmonary embolism which had occurred after various operations. In two
      cases, dehydration due to either diabetes insipidus or ileus had existed. In two
      cases, pulmonary embolism suddenly occurred in our hospital. In the remainder,
      the disease occurred in the previous hospitals and its diagnosis was established
      on the 6th and 7th postoperative days, respectively. In massive pulmonary
      embolism, echocardiography and/or enhanced chest CT are useful for prompt and
      noninvasive diagnosis. Thrombolytic therapy was performed in only one case before
      surgical embolectomy, which was not effective. Three patients were discharged
      without any postoperative complications, but one requiring preoperative external
      cardiac massage died of multiple organ failure 9 days after operation. Acute
      pulmonary embolism is one of the fatal postoperative complications. Recognition
      of this entity, and prompt diagnosis and treatment are essential for managing the
      fatal disease. Even in the early postoperative period, embolectomy using
      cardiopulmonary bypass is a safe and effective treatment.

PMID- 11244747
TI  - [Renal autotransplantation in a patient with acute renal infarction following
      surgery for a dissecting aneurysm].
AB  - A 58-year-old woman experienced a sudden onset of severe chest and back pain and
      thus visited our center in October 1999. Contrast-enhanced computed tomography
      (CT) revealed a Stanford type A acute aortic dissection. The CT also demonstrated
      a 50 mm ascending aorta and dissection from the ascending aorta via the abdominal
      aorta to the level of the left renal artery. The perioperative transesophageal
      echocardiogram showed an intimal tear in the ascending aorta without valvular
      abnormality. Therefore, we performed graft replacement of the ascending aorta. On
      the first postoperative day, she developed oliguria and showed a sudden rise in
      serum creatinine (Cr) and blood urea nitrogen (BUN) levels, necessitating
      hemodialysis. She required daily hemodialysis or hemofiltration for twenty days.
      Thereafter, renal function recovered and dialysis was no longer performed.
      However, on postoperative day 26, the patient complained of sudden lumber pain.
      Unheralded oliguria was associated with worsening renal function. A CT scan at
      this point revealed infarction of the left kidney. During surgery, the left
      kidney was excised for heterotopic autotransplantation. Extensive thrombosis
      within a true lumen of the left renal artery was revealed. Following removal of
      the thrombus and perfusion with heparinized cold saline, renal
      autotransplantation to a heterotopic site in the pelvis were performed. Although
      the patient required hemodialysis for five days, renal function recovered
      gradually. She was discharged five months later. In our experience, it appears
      that heterotopic renal autotransplantation by which normal arterial perfusion
      distal to the dissection is reestablished is a good therapeutic option for
      reperfusion of the ischemic kidney compromised by a progressive dissection of the
      thoracoabdominal aorta.

PMID- 11244748
TI  - [A case of primary malignant fibrous histiocytoma of the lung].
AB  - A 68-year-old woman presented with a complaint of coughing and
      chestroentgenography and computed tomography revealed a very large, irregular
      mass in the left inferior lobe of the lung. The suspected preoperative diagnosis
      was sarcoma. Therefore, a complete resection of that mass was considered to be
      difficult. The patient received preoperative chemotherapy including cisplatin
      with vindesine as employed for non-small cell lung cancer. She demonstrated a
      clinical response after three cycles of the chemotherapy and underwent surgery
      successfully. A postoperative diagnosis of MFH was made based on the histology of
      the tumor, which was pleomorphic with a storiform pattern. The tumor cells showed
      positive immunostaining for alpha 1-antitrypsin and alpha 1-antichymotrypsin but
      were negative for SMA and S-100 protein. The patient underwent a further three
      cycles of postoperative chemotherapy and has remained disease-free for 12 months
      after tumor resection.

PMID- 11244749
TI  - [A tube retractor for cardiac surgery].
AB  - A retractor exclusively used to retract the tubes in cardiac surgery which needs
      cardiopulmonary bypass was developed. The half-cylinder-shaped end, the lightly
      curved handle and the flat and triangular grip enable easy and effective grasp of
      the tubes. This new instrument facilitates operative procedures by effectively
      retracting the tubes which persistently obstruct the operative field, in such a
      case of placement of a retrograde cardioplegia tube via the right atrium.

PMID- 11244750
TI  - [Limited thoracotomy as surgical therapy for lung cancer: lobectomy and lymph
      node dissection by means of 12 cm skin incision].
AB  - In the domain of respiratory surgery minimally invasive approaches are currently
      being used and video-assisted thoracic surgery (VATS) is one of these methods.
      However VATS has some problems in its use for malignant lung diseases for
      example, with VATS adequate lymph node dissection and continuation of lobectomy
      in cases with severe adhesion are both difficult. In consideration of these
      points, limited thoracotomy has been practiced for treatment of lung cancer in
      our hospital. This study made comparisons between this new method (group A) and
      the conventional standard thoracotomy (group B). For the limited thoracotomy
      group (A) the skin incision and amount of bleeding were smaller than for the
      standard thoracotomy group (B) and the operation time was shorten. All limited
      thoracotomy group patients could lift up and move the hand of the affected side
      without pain immediately after the operation. The limited thoracotomy is an
      excellent approach as a curative operation for lung cancer, for preservation of
      post-operative pulmonary function, for movement capacity of the hand of the
      affected side and from the cosmetic viewpoint.

PMID- 11244751
TI  - [Preoperative autologous blood donation in elderly patients with cardiovascular
      surgery].
AB  - BACKGROUND: During the cardiovascular surgeries in elderly people, only a few
      cases can avoid the homologous blood transfusion, because of their preoperative
      anemic tendency and low hemopoietic abilities. We examined the capability to
      avoid the homologous blood transfusion in over 75 year old patients by the
      preoperative autologous blood collection. Sixty-six patients underwent scheduled
      cardiovascular surgery between January 1996 and December 1999. The groups were
      divided into three categories of preoperatively collected autologous blood
      amounts: high-amount (800-1,200 ml), medium-amount (200-800 ml), and low-amount
      (0 ml). Each group was divided into two subgroups in according to the use of
      cardiopulmonary bypass (CPB). There were no differences among the each group in
      age, body weight, or preoperative and postoperative day-7 hematocrit values.
      RESULTS: Only 21.2% of patients could donate the expected blood amounts
      preoperatively. Mean volume was 641 ml. In groups used CPB, no patient was
      transfused homologous blood in high-amount group. On the contrary, 100% patients
      were donated in medium and low amount groups. In groups operated without CPB,
      homologous blood transfusion was required 14.3% in high-amount group, 25.0% in
      medium-amount group, and 83.3% in low-amount group. CONCLUSION: It seems that
      predonation of more than 800 ml may be sufficient to avoid the homologous blood
      transfusion in using CPB operation and more than 400 ml in non using CPB
      operation.

PMID- 11244752
TI  - [Is open heart surgery clean: bacteriologic analysis of salvaged blood].
AB  - In this prospective study, we evaluated contamination of surgical fields in open
      heart operations by salvaged blood culture used in autologous transfusions device
      (Cell Saver 5, Heamonetics Corp., Braintree, MA, USA). And also, we prospectively
      investigated an efficacy of pre- and intra-operative prophylactic antibiotics
      administrations (cefazolin). Thirty patients undergone open heart surgeries with
      median sternotomy enrolled in this study. The patients were divided into two
      groups, group A (n = 15); without prophylactic antibiotics administration, group
      B (n = 15); with pre- and intra-operative prophylactic antibiotics
      administrations. Blood samples were drawn through the right atrium after the
      discontinuation of CPB and from salvaged blood bags. Bacterial growth was
      detected in 80.0% of salvaged blood samples in group A, 86.7% in group B (p =
      0.62). Whereas no bacterial growth detection in blood samples though the right
      atrium. Quantitative estimates of contaminations showed 1.06 +/- 1.41, 0.90 +/-
      1.24 cfu/ml, respectively (p = 0.22). Although bacterial growth rate were not
      statistically significant difference between groups, detective rate of
      Staphylococci was remarkably decreased (p = 0.005) in group B. Pre- and intra
      operative prophylactic antibiotics administrations were effective for
      Staphylococci, but not whole microorganisms. In conclusion, salvaged blood used
      in autologous transfusions was highly contaminated and it suggests that surgical
      fields were not clear. Prophylactic antibiotics administrations were effective
      especially for Staphylococci.

PMID- 11244754
TI  - [Two cases of left main trunk lesion treated with coronary artery bypass grafting
      the proximal circumflex coronary artery (# 11)].
AB  - Two cases are reported of coronary artery bypass graft (CABG) surgery to the
      proximal left circumflex artery (LCX) system and left anterior descending artery
      (LAD) system. Both patients suffered from unstable angina due to left main trunk
      (LMT) lesions and required semi-emergent coronary revascularization. In both
      cases, the obtuse marginal branch and postero-lateral branch were too small to be
      grafted, although there are the usual target branches in the LCX system. CABG to
      the proximal portion (# 11) of LCX in the atrioventricular groove using saphenous
      vein grafts was performed and good blood flow rates were seen intra-operatively.
      Both patients recovered uneventfully and had no recurrence of anginal attacks.
      Postoperative coronary angiography confirmed good graft patency and an adequate
      coronary blood supply. CABG to LCX (# 11) is feasible without special techniques
      or tools. This method seems to be useful in patients with LMT lesions or with
      proximal lesions of LCX in which the branches are too small to be grafted.

PMID- 11244753
TI  - [Evaluation of superior transseptal approach for the removal of left atrial
      myxoma].
AB  - We compared the operative outcomes among 14 patients who underwent the removal of
      left atrial myxoma with four different approaches; right lateral (n = 2),
      transseptal bi-atrial (Dubost, n = 4), conventional transseptal (n = 4) and
      superior transseptal approach (STA, n = 4). Concomitant operations were performed
      in 4 cases (CABG, two; aortic valvuloplasty, one; mitral valve replacement, one),
      and two out of 4 cases were in the STA group. The mean operation, cardiopulmonary
      bypass and aortic cross-clamp times were shorter in the STA group compared to the
      other three group. The total amount of postoperative drain discharge and the peak
      value of creatine kinase were also lower in the STA group compared to the other
      three groups. Among the patients in sinus rhythm before operation, the use of STA
      was associated with a greater incidence (100%) of postoperative atrial
      fibrillation or junctional rhythm. These rhythm disturbances were temporary, and
      all returned to sinus rhythms during hospital stay. We conclude that STA is an
      excellent approach with a nice surgical view to expose and remove the left atrial
      myxoma.

PMID- 11244755
TI  - [Lobectomy of two or more lobes in patients with lung cancer].
AB  - We clinically examined patients who had undergone resection of two or more lobes
      for lung cancer. The subjects were 50 patients (25 who underwent pneumonectomy
      and 25 bilobectomy) who underwent lobectomy of two or more lobes from among those
      with primary non-small cell lung cancers in our hospital between 1975 and 1999;
      these individuals were assigned to Group A, and compared with 166 patients with
      lobectomy in Group B. The five-year survival rate was 27.7% in Group A, which
      differed significantly from the rate of 55.6% in Group B (p < 0.01, Kaplan-Meier
      method with log-rank test). The percentage of Stage I patients was 34% (17
      patients) in Group A and 60.2% (100 patients) in Group B: this difference was
      significant (chi 2 test, p < 0.01). There were more patients with advanced cancer
      in Group A than in Group B. However, the five-year survival rates of Stage I
      patients were 52.4% in Group A and 77.6% in Group B, and significantly different
      (p < 0.05). In a comparison with respect to histological type, the five-year
      survival rates also differed significantly between Group A and B (p < 0.01 for
      adenocarcinoma, p < 0.05 for squamous cell carcinoma, with higher values in Group
      B for both). Resection of two or more lobes was indicated based on infiltration
      of the main tumor into adjacent lobes in 19 patients (38%), infiltration of lymph
      node metastasis into a bronchus or pulmonary artery in 14 (28%), direct
      infiltration of the main tumor into a bronchus in 10 (20%), and for other reasons
      in 7 (14%). The five-year survival rates for these groups were 15.8, 22.1, 54 and
      42.9%, respectively. There was a significant difference between the patients with
      infiltration of cancer into adjacent lobes and those with direct infiltration
      into a bronchus (p < 0.05). The prognosis of patients with resection of two or
      more lobes was poorer than that of patients with lobectomy even in Stage I. In
      particular, infiltration of cancer into adjacent lobes accompanied lymph node
      metastasis in more than 50% in cases, and appeared to suggest a poor prognosis.

PMID- 11244756
TI  - [A case report of total repair in a 71-year-old patient with tetralogy of
      Fallot].
AB  - A 71-year-old male is presented as ever the oldest patient of tetralogy of Fallot
      who underwent successful radical surgery. Heart murmur was pointed out at the age
      of 10 years. The patient consulted us because of dyspnea and cough, and was noted
      to have cyanosis and clubbing fingers. Polycythemia was also detected by
      hemoglobin of 20.8 g/dl and hematocrit of 58.4%, and a low PaO2 of 48.5 mmHg at
      room temperature was pointed out. Preoperative echocardiography and cardiac
      catheterization indicated a ventricular septal defect, overriding of the aorta,
      and right ventricular outflow tract stenosis with a pressure gradient of 115 mmHg
      between the right ventricle and the main pulmonary artery. Under cardiopulmonary
      bypass, the ventricular septal defect was closed with a dacron patch and the
      right ventricular outflow tract was enlarged by a patch of collagen-coated
      vascular graft with a commissurotomy of the pulmonary valve. Postoperatively,
      cyanosis disappeared and the pressure gradient was decreased to 26 mmHg.

PMID- 11244758
TI  - [Surgical treatment for chronic pulmonary thromboembolism in a patient with
      protein C deficiency].
AB  - Medical therapy for chronic pulmonary thromboembolism is limited, and surgical
      treatment has become more frequent recently. We have performed pulmonary
      thromboendarterectomy on a patient with chronic pulmonary thromboembolism
      accompanied by protein C deficiency. The patient was a woman aged 68 years who
      had protein C deficiency. The preoperative condition was New York Heart
      Association functional class IV. Hypoxemia, marked pulmonary hypertension, and
      low cardiac output were observed. After a median sternotomy, moderate hypothermia
      was induced using a cardiopulmonary bypass, and thromboendarterectomy in the
      pulmonary artery was performed. The arterial blood oxygen concentration improved,
      and the mean pulmonary pressure decreased. The cardiac output also increased, and
      New York Heart Association functional class improved to I. Pulmonary
      thromboendarterectomy under cardiopulmonary bypass was effective for chronic
      pulmonary thromboembolism accompanied by protein C deficiency.

PMID- 11244757
TI  - [A case of free-floating ball thrombus in left atrium with mitral stenosis].
AB  - We report a rare case of free-floating ball thrombus in the left atrium with
      mitral stenosis. The patient was 71-year-old woman who admitted to the local
      hospital for transient ischemic attack. Electrocardiography showed atrial
      fibrillation and an echocardiogram examination revealed free-floating ball
      thrombus in the left atrium with mitral stenosis. She was transferred to our
      hospital for emergency open heart operation. After removal of the ball thrombus,
      mitral valve replacement and modified MAZE procedure were successfully performed.
      The size of the ball thrombus was 40 x 30 x 33 mm and weighed 20 g. Postoperative
      course was uneventful.

PMID- 11244759
TI  - [Case report of a malfunctioning SJM 19 A aortic valve prosthesis requiring
      reoperation].
AB  - The patient was a 56-year-old female diagnosed with poor lung function who had
      undergone an aortic valve replacement 10 years ago, receiving an SJM 19 A
      prosthetic valve. She suffered from dyspnea and chest pain with postural change.
      Her anticoagulation level was maintained therapeutic. A cinefluoroscopy showed
      that one of the leaflets in the prosthetic valve was not moving. The aortic peak
      pressure gradient was calculated to be 68 mmHg using Doppler echocardiography.
      The patient's clinical condition improved after thrombolytic therapy with
      urokinase, but a complete normalization of her prosthetic discs was not obtained,
      so the patient was treated surgically. After an aortotomy, a pannus formation
      covering the entire SJM 19 A valve was observed. The aortic annulus was estimated
      to be 16 mm in diameter after the excision of the SJM 19 A valve and required
      before a larger prosthesis could be inserted. A SJM 19 HP valve was then anchored
      to the enlarged annulus. Her postoperative course was uneventful. We report a
      case requiring reoperation after a small aortic mechanical valve prosthesis
      implanted 10 years previously was damaged by thrombosis and pannus. Pannus
      formation on small aortic prosthesis easily caused hemodynamic obstructions and
      mechanical failure. Intensive evaluation with Doppler echocardiography and
      cinefluoroscopy is required for such patients.

PMID- 11244760
TI  - [A case of Castleman lymphoma in the right pulmonary hilum and mediastinum].
AB  - A 36-year-old man who complained of low grade fever and cough was detected an
      abnormal shadow in the right pulmonary hilum and mediastinum on a chest X-ray
      film. On admission, laboratory data showed high CRP and hyper gamma globlinemia.
      In thoracotomy, original tumor and mediastinal lymph node were resected.
      Histopathologically, main tumor and two of all the resected lymph node were
      diagnosed as Castleman lymphoma (plasma cell type). We consider that not only the
      main tumor and also the peripheral lymph node should be resected in this disease,
      because the lesions were often showed multicentric if this tumor were plasma cell
      type.

PMID- 11244761
TI  - [A case of giant cell tumor originating from the rib].
AB  - We have experienced a case of giant cell tumor originating from the rib. A 45
      year-old male was admitted to our hospital because of a mass in the left chest
      wall. A tumor shadow was observed in the left side of chest X ray. Chest CT, bone
      scintigram showed tumor originating from the left 4th rib. The tumor was
      suspected giant cell tumor of bone by needle biopsy examination. The tumor was
      completely resected with chest wall surrounding the tumor. The defect of chest
      wall was reconstructed with Marlex mesh and the Latissimus dorsi muscle flap. The
      pathological diagnosis was a giant cell tumor of bone. The patient has been well
      for two years and one month since surgery, with no signs of recurrence.

PMID- 11244762
TI  - [Traumatic diaphragmatic herniation after continuous thoracic drainage: a case
      report].
AB  - We report a case of traumatic diaphragmatic hernia (TDH) resulting from
      continuous thoracic drainage and was successfully treated by surgical procedures.
      A 45-year-old man was admitted to our department due to shock after a blunt
      trauma by a traffic accident. As he revealed left hemothorax on admission,
      continuous thoracic drainage was performed. Soon after the drainage,
      diaphragmatic hernia occurred as an incarceration of the spleen into the thoracic
      cavity. In the literature, 80 cases with TDH have been reported in Japan since
      1986. The purpose of this study is to discuss the mechanism of TDH in the acute
      phase and to consider its appropriate diagnostic tools. The following two results
      were obtained. (1) TDH may be appeared during the clinical course, especially
      after a continuous thoracic drainage, in patients with damaged diaphragm by blunt
      traumas. (2) CT is the most effective tool for the diagnosis of TDH.

PMID- 11244763
TI  - [Effects of positive end-expiratory pressure, tidal volume and perflubron doses
      on gas exchange during partial liquid ventilation].
AB  - The efficacy of gas exchange during partial liquid ventilation (PLV) may be
      affected by positive end-expiratory pressure (PEEP), tidal volume (TV) and
      perflubron (PFOB) dose. The purpose of the present study was to clarify which
      factors were important for improving gas exchange during PLV. Fourteen rabbits
      were anesthetized and tracheostomized. Lung was introduced with intravenous oleic
      acid combined with saline lung lavage. After obtaining control data, PFOB 7.5
      ml.kg-1 was instilled into the trachea, and ventilation settings were changed
      sequentially [1. TV: 10 ml.kg-1 (mTV), 2. mTV with PEEP, 3. TV: 15 ml.kg-1 (hTV),
      4. hTV with PEEP]. PEEP level was set to the lower inflection point. The PFOB
      dose was increased to 15 ml.kg-1 and measurements were repeated under each
      ventilation setting. PEEP increased PaO2 in all ventilation settings. In hTV
      ventilation settings, incremental dose of PFOB significantly increased PaO2. The
      PaO2 values of all hTV ventilation settings were significantly higher than those
      of corresponding ventilation setting of mTV. Pulmonary compliance was
      significantly decreased with PEEP in hTV ventilation in addition to 15 ml.kg-1
      PFOB. The results suggested that adequate gas tidal volume was the most important
      factor for improving gas exchange during PLV. However, PEEP or larger dose of
      PFOB should be avoided because they may decrease pulmonary compliance.

PMID- 11244764
TI  - [Effects of dopamine and dobutamine on renal function and urinary excretion of
      prostaglandin E2 in elderly postoperative patients].
AB  - Effects of dopamine and dobutamine on renal function and urinary excretion of
      prostaglandin E2 (UPGE) were studied in 21 elderly patients who underwent
      abdominal surgery. Fractional sodium excretion (FeNa), creatinine clearance
      (Ccr), urinary volume (UV, ml.kg-1.min-1) and UPGE were measured on the first and
      second postoperative day. These patients were divided into three groups: i.e. C
      (control), DA (dopamine) and DB (dobutamine) groups. Group DA received dopamine 2
      mcg.kg-1.min-1 beginning at six o'clock on the first postoperative day. Group DB
      received dobutamine 2 mcg.kg-1.min-1. There were no significant differences in UV
      and UPGE among these three groups. Ccr was significantly higher on the second
      postoperative day than that on the first postoperative day in DA group. FeNa in
      DA group was higher than in C group on the second postoperative day. The
      relationship between UPGE and UV was not determined. These results suggest that
      DA improve renal functions in the elderly.

PMID- 11244765
TI  - [Clinical evaluation of roxatidine acetate hydrochlorides as a preanesthetic
      medication].
AB  - Roxatidine acetate hydrochloride capsule is slowly absorbed from the
      gastrointestinal tract, and its acid suppressive effect on the stomach is long
      lasting compared with other H2-blockers. The reduction of gastric juice in
      perioperative period is considered advantageous for patients not only because it
      decreases the risk for aspiration pneumonia but also because it reduces the risk
      of bronchial spasm induced by gastroesophageal reflux of acidic gastric content.
      The effects of single oral administration of roxatidine acetate hydrochloride 150
      mg at night before the operation on the volume and pH of gastric juice were
      investigated during anesthesia using two types of anesthetic agents (isoflurane
      and propofol) in 93 patients of three age groups (group Y: age 20-40, group M:
      age 41-64, group O: age 65 <). The effect of roxatidine on reduction of gastric
      juice was found at the time of anesthetic induction and 2 hours after the
      induction in any age group with either anesthetic agent. The serum concentration
      of roxatidine at the time of induction was much higher in group O. The value of
      residual concentration of roxatidine 20 hours after oral intake was estimated
      from the intraoperative measurements of serum concentration. The results suggest
      that single administration at night before the operation is sufficient for the
      oldest group, but an additive dose is recommended for the younger groups.

PMID- 11244766
TI  - [Comparative survey of cardiac arrests during anesthesia and surgery in the 1980
      s and 1999 s].
AB  - A survey of unexpected cardiac arrests, excluding those associated with cardiac
      surgery, that had occurred during anesthesia and surgery in the period 1980-1999
      was conducted. There was no significant difference between the number of such
      cardiac arrests that occurred in the 1980 s (29/36,159, 0.080%) and the number in
      the 1990 s (33/37,643, 0.088%). According to the classification by Keenan et al.,
      there were 3 cases (0.0083%) in the 80 s and 4 cases (0.0106%) in the 90 s that
      occurred due to anesthetic management. Cardiac arrests due to surgery itself
      significantly decreased from 21 cases in the 80 s to 6 cases in the 90 s,
      probably due to proper treatment for massive bleeding, a decrease in the number
      of cases of anaphylactic shock, and the development of novel anesthetics.
      Conversely, cardiac arrests due to preoperative conditions of the patients
      significantly increased from 5 cases in the 80 s to 23 cases in the 90 s. This
      increase seems to be due to an increase in the number of severe and multiple
      injuries and an increase in complicated major surgery. The increase in number of
      cases due to preoperative conditions also depends on coronary spasm and cardiac
      conduction insufficiency. Taking into consideration the improvement in
      intraoperative monitoring and the development of novel anesthetics in the 90 s,
      greater efforts should be made by anesthesiologists to reduce the incidence of
      cardiac arrest due to anesthetic management, and preoperative evaluation of
      surgical patients needs to be reconsidered.

PMID- 11244767
TI  - [Anesthetic management of two patients with insulinoma using propofol--in
      association with rapid radioimmunoassay for insulin].
AB  - We experienced anesthetic management of two patients with insulinoma in whom
      frequent hypoglycemic episodes with blood glucose levels of 39-42 mg.dl-1 had
      been observed. Each patient received epidural analgesia with a catheter inserted
      at the T 9/10 intervertebral space. Anesthesia was induced with propofol 80-100
      mg and fentanyl 200 micrograms. Tracheal intubation was facilitated with
      vecuronium 6 mg. Anesthesia was maintained with continuous infusion of propofol
      and epidural anesthesia. Rapid measurements of immunoreactive insulin (IRI) were
      useful for localization of insulinoma during surgery. Perioperative plasma
      glucose levels could be maintained within normal ranges by continuous infusion of
      glucose. Rebound hyperglycemic episodes were not observed, and IRI was reduced
      after removal of the insulinoma. General anesthesia using propofol and epidural
      block is a useful choice for the anesthetic management of patients undergoing an
      operation for removal of an insulinoma.

PMID- 11244769
TI  - [Perioperative management of three patients with streptococcal toxic shock
      syndrome].
AB  - We report the perioperative management of three patients with streptococcal toxic
      shock syndrome (STSS) caused by group A streptococcal infection. Three of two
      patients survived but one patient died from multiple organ dysfunction in spite
      of vigorous treatments. These patients required the treatments including
      administration of antibiotics, circulatory and respiratory care, surgical
      debridement, anticoagulant therapy for disseminated intravascular coagulation and
      hemofiltration. The early diagnosis and surgical intervention play a key role in
      the successful management of this syndrome because it has a rapid course and
      frequent fatal outcome. The anesthetic management of these patients should be
      targeted to maintain perfusion of the vital organs and to control the blood
      clotting disorders.

PMID- 11244768
TI  - [Anesthetic management for left ventricular assist device implantation in
      patients waiting for heart transplantation].
AB  - We report the anesthetic management of patients with dilated cardiomyopathy who
      underwent left ventricular assist device implantation (LVAD). Anesthesia was
      induced and maintained with midazolam and fentanyl. Transesophageal
      echocardiography (TEE) and a PA catheter were useful for hemodynamic monitoring
      and management of the patients. Furthermore, TEE is useful for the early
      detection of inflow of the air which is absorbed by negative pressure derived
      from high LVAD support pressure. On starting LVAD support, evaluation of right
      ventricular function and treatment for right ventricular failure were important
      and necessary for the patients. Added to conventional therapy using
      catecholamines, inhaled nitric oxide may provide a favorable effect for right
      ventricular failure.

PMID- 11244770
TI  - [Preliminary report: the efficacy of clonidine hydrochloride ointment for
      postherpetic neuralgia].
AB  - The combination of clonidine hydrochloride, alpha 2-agonist, and opioid is useful
      for relieving the pain due to surgical procedures or cancer. The routes of
      administrations used are intravenous, intramuscular as well as intrathecal,
      epidural and transmucosal. However, transdermal clonidine has not been reported.
      We, therefore, investigated the analgesic effect of local administration of
      clonidine ointment. Ten patients with postherpetic neuralgia (PHN) were selected
      randomly. They were requested to fill out a questionnaire after applying
      clonidine ointment (150 micrograms/ointment 1 g) to the painful area. Items
      included in the questionnaire were: effectiveness, visual analog scale (VAS)
      before and after the administration of clonidine ointment, onset time, with or
      without allodynia and effectiveness to allodynia in the former case, side
      effects, and patients' background. Analysis of the answers indicates that
      clonidine ointment produced a satisfactory effect in nine patients. Onset time
      was within a few minutes in most patients. No patients suffered any side effects.
      Specific mechanism of effectiveness or the site affected has not been confirmed
      in this study, but considering the quick onset, it is presumed that the site
      where the ointment was applied was the very site that was affected. Clonidine
      hydrochloride ointment was effective in relieving the symptoms of PHN.

PMID- 11244771
TI  - [Preliminary report: the effect of flumazenil on the hypnotic dose of propofol in
      ddY mice].
AB  - The present investigation dealt with the effect of simultaneous administration of
      flumazenil on the hypnotic activity of propofol using a behavioral model of ddY
      mice. The mixed solution of propofol and flumazenil was administered
      intravenously into the mice tail vein and the achievement of hypnosis was defined
      as the loss of the righting reflex. Flumazenil 0.2 mg.kg-1 significantly
      decreased the required dose of propofol for hypnosis (8.43 +/- 0.46 mg.kg-1)
      compared to the control group (10.55 +/- 0.55 mg.kg-1). The mixture with a pH-3.9
      acetate buffer solution did not change the hypnotic dose of propofol (10.88 +/-
      0.62 mg.kg-1). The results suggest that flumazenil might potentiate the hypnotic
      activity of propofol in ddY mice.

PMID- 11244772
TI  - [Generalized tonic-clonic seizure induced by propofol in a patient with
      epilepsy].
AB  - A 47-year-old female was scheduled for ulnar osteotomy under general anesthesia
      combined with brachial plexus block. She had a history of symptomatic epilepsy
      due to subarachnoid hemorrhage. Immediately after giving 100 mg bolus of propofol
      to the patient, she developed generalized convulsion similar to a grand mal. The
      seizure was suppressed by the administration of thiamylal. After that no further
      convulsive attack occurred. Although it has been known that propofol has
      anticonvulsive properties, there have been several reported cases of seizure
      following the administration of propofol. Further studies are needed to clarify
      the mechanism of seizure induced by propofol in the patients with epilepsy.

PMID- 11244774
TI  - [Finding appropriate endotracheal tube position by Trachlight in children].
AB  - Finding appropriate endotracheal tube position in children is important, because
      the trachea length of a child is shorter than that of an adult, and the position
      of the endotracheal tube is easy to be altered by head position, rotary
      movements, and flexion as well as extension. We confirmed the correct depth of
      the endotracheal tube by transillumination method using the Trachlight device in
      children. Twenty children were intubated orally with a rigid laryngoscope
      according to the distance of the formula height/10 + 5 cm at the lips. We
      measured the distance from the tip of the tube to the sternal notch where the
      bright light of the Trachlight disappeared. The tip of the endotracheal tube
      (4.5, 5.0 or 5.5 mm tube size) was placed approximately 1.5 cm beyond the sternal
      notch. The distance between the carina and the tube tip measured by chest
      radiography was more than 1 cm. Trachlight device was simple and reliable to
      ensure the appropriate endotracheal tube position in children. We consider that
      the appropriate depth of the endotracheal tube using any of 4.5, 5.0 or 5.5 mm
      tube size is 1.5 cm beyond the point the bright light of the Trachlight
      disappears.

PMID- 11244773
TI  - [Anesthetic management for the correction of pectus excavatum using pectus bar
      under video-assistance].
AB  - We report anesthetic management for a child undergoing Nuss operation, a
      minimally invasive operation which requires neither cartilage incision nor its
      resection for correction of pectus excavatum. The patient was a 7-year-old boy
      with the funnel index 5 and the mediastinal shift to the left. General anesthesia
      with endotracheal intubation was induced and maintained with nitrous oxide,
      sevoflurane and fentanyl. Thoracic epidural anesthesia was used with 0.125%
      bupivacaine to supplement analgesia. When the curved bar was passed under the
      sternum with the aid of an endoscope, sinus tachycardia occurred and continued
      for 5 minutes but subsided without medication. Otherwise operative course was
      uneventful with negligible blood loss. After surgery, the patient was kept at bed
      rest for 2 days, receiving epidural patient-controlled analgesia combined with
      sedation with midazolam with good results. He was allowed to sit 3 days, to walk
      5 days and discharged 10 days postoperatively.

PMID- 11244775
TI  - [Heparin concentration and hemostatic alterations with low systemic
      heparinization during CPB using heparin-coated circuits].
AB  - Extracorporeal circulation with heparin coated circuits allows reduction of
      systemic heparin. The authors investigated the effects of this method on the
      hemostatic and fibrinolytic systems and heparin concentration simultaneously. Ten
      patients undergoing coronary artery bypass surgery were studied. The dose of
      heparin was 100 IU.kg-1, and the target activated clotting time (ACT) was more
      than 300 seconds. Blood samples were obtained at the following times; before and
      after giving heparin, 10 and 40 minutes after the start of extracorporeal
      circulation, after cross-clamp release, and after giving protamine, and heparin
      concentration, ACT, thrombin-antithrombin complex (TAT), plasmin alpha 2 plasmin
      inhibition complex (PIC), and D-dimer were measured. ACT was kept over 300
      seconds without additional heparin administration. Heparin concentration was
      maintained at 1.0 IU.ml-1. However, after release of the aortic cross-clamp, TAT,
      PIC, D-dimer increased significantly. Despite reduced systemic heparinization,
      heparin concentration was maintained adequately. Thrombin generation and
      fibrinolytic activity showed no significant increase until the release of the
      aortic cross-clamp.

PMID- 11244776
TI  - [Left main coronary trunk compression by dilated main pulmonary artery in a
      patient with atrial septal defect].
AB  - A 12-year-old girl with atrial septal defect combined with pulmonary hypertension
      and 90% stenosis of the left main coronary artery caused by dilated pulmonary
      artery was scheduled for atrial septal closure and coronary artery bypass graft
      under general anesthesia. During the echocardiographic examination to evaluate
      the anatomical relationship between the pulmonary artery and left main coronary
      trunk, bradycardia and a depression of ST-segment on electrocardiogram appeared
      suddenly when the operator compressed the pulmonary artery with a probe of
      echocardiography from the operative field. The circulatory collapse and ischemic
      change on electrocardiogram might have been caused by a further reduction of
      blood flow to the left main coronary trunk narrowed originally by dilated
      pulmonary artery. Although various etiologies, such as atherosclerosis, syphilis,
      and congenital abnormalities are widely known to cause stenosis of the left main
      coronary trunk, external compression by dilated pulmonary artery has not been
      widely known. Malignant arrhythmias from coronary artery compression with
      subsequent ischemia could contribute to an incidence of sudden death. Coronary
      angiography and magnetic resonance imaging are useful for the preoperative
      evaluation. Careful management is needed to protect such a patient from ischemic
      event in the perioperative period.

PMID- 11244777
TI  - [Efficiency of bispectral index in anesthetic management of a patient with
      hypothyroidism].
AB  - A 72-year-old, female patient with severe hypothyroidism underwent tracheostomy
      using deltopectral flap. During the anesthetic management, we assessed the
      hypnotic level using the bispectral index and regulated the dose of general
      anesthetics to maintain the bispectral index at about 50. The general anesthetics
      caused a marked cardiovascular depression, but the condition was treatable with
      the intravenous administration of dopamine. Using these methods, we could
      anesthetize this patient safely without a prolonged awakening time from general
      anesthesia. Although the anesthetic requirement for patients with hypothyroidism
      is generally thought to be decreased, there is no practical index by which we can
      estimate the optimal dose of anesthetic agents for these patients. This case
      report shows that the assessment of the hypnotic level by the bispectral index
      can be utilized as an efficient index to determine the optimal dose of general
      anesthetics for patients with hypothyroidism.

PMID- 11244778
TI  - [Anesthetic management of a patient with pheochromocytoma and cerebral ischemic
      attacks].
AB  - A 15-year-old girl with history of two cerebral ischemic attacks possibly caused
      by cerebral vascular spasm was diagnosed as having a pheochromocytoma, and was
      scheduled for laparoscopic removal of the adrenal tumor. Epidural catheterization
      was performed at Th 12/L 1. General anesthesia was induced with thiamylal and
      vecuronium, and maintained with nitrous oxide-oxygen-isoflurane and continuous
      epidural infusion of 1.5% lidocaine. Phentolamine and thiamylal were continuously
      administrated into the vein. While operating on the tumor, abnormal hypertension
      did not occur. Just after removal of the tumor, the systolic blood pressure fell
      to 50-70 mmHg. The hypotension continued for about 75 min, despite administration
      of dopamine, norepinephrine and epinephrine. After the emergence from anesthesia,
      the blood pressure recovered to normal level. No neurocerebral abnormality was
      found. In patients like this one, we have to prevent cerebral vascular spasm and
      cerebral infarction caused by excessive secretion of catecholamines.

PMID- 11244779
TI  - [A case of cardiac arrest with coronary artery spasm during lumbar epidural
      anesthesia].
AB  - A 61-year-old man underwent arthroscopic surgery for internal derangement of the
      knee joint under epidural anesthesia. Epidural catheterization was performed at
      the L 2-3 interspace. Operation was started with 10 ml of 1.5% lidocaine. Then 12
      ml of 0.375% bupivacaine was added to epidural space. Twenty minutes thereafter,
      electrocardiogram demonstrated marked elevation of ST segment and atrio
      ventricular dissociation, followed by cardiac arrest. Cardiopulmonary
      resuscitation was started immediately and after 25 minutes normal sinus rhythm
      was restored. The patient recovered with no neurological sequelae. Coronary
      angiogram examination was performed but no significant stenosis of coronary
      artery was observed. Coronary artery spasm caused by lumbar epidural anesthesia
      was suspected.

PMID- 11244780
TI  - [Propofol pharmacokinetics in a patient with TSH producing pituitary adenoma].
AB  - We investigated propofol pharmacokinetics in a patient with secondary
      hyperthyroidism caused by thyroid stimulating hormone (TSH) producing pituitary
      adenoma. Laboratory data indicated thyrotoxic state with elevated TSH, FT3 and
      FT4 levels. General anesthesia was maintained with a doubled propofol infusion
      rate (8-10 mg.kg-1.hr-1) compared to our standard procedure. During 370 min of
      infusion, propofol concentrations in arterial blood were kept within optimal
      ranges (2-4 micrograms.ml-1). Although the clearance of propofol was high (2.8
      l.min-1) because of the thyrotoxic state, the patient showed delayed recovery
      from anesthesia. The half-life of blood propofol after the termination of
      infusion exceeded 30 minutes (normal: 10-15 minutes). We conclude that the
      delayed recovery was due to the accumulation of propofol in the adipose tissue
      during long-term infusion in spite of the increased propofol clearance.

PMID- 11244781
TI  - [Notes about two paintings in the Francis A. Countway Library of Medicine].
AB  - Two interesting mural-sized oil paintings hang in the Francis A. Countway Library
      of Medicine in Boston. One is "The First Operation Under Ether" painted by Robert
      C. Hinckley in the nineteenth century, and the other is "The First Successful
      Kidney Transplantation" painted by Joel Babb in 1996. The theme of the former is
      the first operation with ether performed publicly on October 16, 1846, at the
      Massachusetts General Hospital. That of the latter is the first successful renal
      transplantation between identical twins performed at the Peter Bent Brigham
      Hospital on December 23, 1954. "The First Operation Under Ether" was recreated by
      the painter, Robert Hinckley, who gathered information by himself about the
      event, which had occurred over three decades previously in his hometown. He
      seemed to have exercised some degree of artistic license in recreating the scene.
      On the other hand, "The First Successful Kidney Transplantation" was planned by
      the three doctors who were themselves involved in the memorable operation. The
      painter, Joel Babb, began to recreate the scene after he had been handed some
      sketches and photos of the event and several photos of the participants. In this
      case, it seems that authenticity was the main consideration.

PMID- 11244782
TI  - [An automated electronic anesthesia record and automated urine output
      measurement].
AB  - We can now collect many parameters (NIBP, HR, ABP, SpO2, EtCO2, CCO, etc) from an
      anesthesia monitor in an automated electronic anesthesia record system. The
      function of automated urine output measurement has been added to an automated
      electronic anesthesia record system. A digital weight meter connected with a
      personal computer by RS-232 C is used to measure the weight of urine. We convert
      the weight to the volume hypothesizing that the density of urine is 1 g.ml-1.
      Physiologic parameters are recorded every 10 seconds from an anesthesia monitor
      and we can set the period of automated urine output measurement we like. We must
      enter the initial and final urine output but the intraoperative urine output is
      collected automatically to an automated electronic anesthesia record and
      visualized in urine bar graph. The total volume of urine is calculated.
      Computerized urine output measurement can record data more frequently, for
      example, every 10 minute. At the end of the operation, intraoperative data are
      sent to a host computer and the anesthesia record is printed. Combining the
      automated urine output measurement with an automated electronic anesthesia record
      system is useful in anesthesia practice of a long operation.

PMID- 11244783
TI  - Evaluation of B7-1 (CD80) and B7-2 (CD86) costimulatory molecules and dendritic
      cells on the immune response in leprosy.
AB  - The cell activation depends on T cell antigen receptor binding to antigen plus
      MHC and costimulation. The binding of CD28, expressed on the T cell surface to B7
      (B7-1 or CD80/B7-2 or CD86) present on the antigen--presenting cells (APCs),
      determines, in several T cell function models, if activation or anergy follows
      antigenic stimulation. In leprosy, the role of CD80 and CD86 as costimulatory
      signal in M. leprae-specific cellular immunity has not yet been defined. We
      investigated the role of B7-CD28 pathway of T cell activation in the in vitro
      response to M. leprae, following stimulation in the presence of monocytes or
      dendritic cells (DCs) as APCs. Monocytes were purified, by cold aggregation, from
      peripheral blood mononuclear leukocytes (PBMC), isolated from leprosy patients.
      In order to obtain DCs, the monocytes were cultured in the presence of IL-4 and
      GM-CSF. T cells were purified from PBMC by negative selection with mABs and C'.
      The phenotype of the cell populations was monitored by FACS. Lymphoproliferative
      assays were performed with T cells, in the presence of monocytes or DCs. The
      cells were stimulated by M. leprae in the presence of anti-CD80 antibody (Ab)
      and/or anti-CD86 antibody (Ab) (Innogenetics). In some experiments Il-10, Il-12
      and anti-Il-12 Ab were also added to the culture. We observed a significantly
      more efficient APC function for DCs when compared to monocytes in T cell in vitro
      responses to M. leprae. Regardless of the clinical form of Leprosy, the M. leprae
      specific immune response was markedly reduced in the presence of anti-CD86 Ab. Il
      12 increase the immune response to M. leprae while IL-10 or anti-IL-12 Ab reduce
      this response when monocytes or DCs were used as APCs.

PMID- 11244784
TI  - Present leprosy situation in India and the decade long experience of this
      correspondent.
AB  - Leprosy, which was known to ancient India as "Kustha Roga" is thought to be its
      origin from India also. It is, still, a major public health problem in India
      affecting many people every year. India is, now, having maximum numbers of
      leprosy cases worldwide and accounts for 67% of total prevalence and 73% of total
      new case dectection. Huge numbers of new cases have been detected in recent years
      (Last year new cases were 782,501) because of adoption of new strategy, Modified
      Leprosy Elimination compaign (MLEC), and effective health education campaign.
      Presently, 70% of the total new caseloads of India are from five most heavily
      infected states. There is significant improvement in the overall situation as is
      evident from steady decline of prevalence rate from 38.6 cases per 10,000
      population in 1985 to 5.0 per 10,000 in 1999.

PMID- 11244785
TI  - [PCR in leprosy].
AB  - Detection of M. leprae DNA using PCR is very sensitive enough to detect very few
      number of bacilli which are not recognized by acid-fast staining method. Because
      the detection of M. leprae is crucial for the diagnosis of leprosy, PCR method
      has been expected to make a diagnosis easy and precise. A new pair of PCR primers
      for M. lepare was selected in the Department of Dermatology, Yokohama City
      University School of Medicine, and many samples obtained from many institutes
      have been examined in the department. In this paper, the PCR method in leprosy is
      discussed, and the results of examination of 59 cases carried out in the
      department from 1994 until 2000 are demonstrated.

PMID- 11244786
TI  - Leprosy elimination in Bangladesh.

PMID- 11244795
TI  - [Image of the month. An unusual cause of asymptomatic pneumothorax].

PMID- 11244796
TI  - [How I treat...congenital cardiopathies in adults].
AB  - Nowadays, the diagnosis of congenital heart disease is generally made in the
      infant, or even at times, in utero. Neonatal surgery has in this field made
      remarkable progresses. In this article, we describe the situation of patients who
      reach the adult age without having their congenital abnormality corrected. Late
      surgery or interventional catheterisation can offer improvement in terms of
      survival and quality of life. It is not always too late to influence the
      patient's prognosis significantly.

PMID- 11244797
TI  - [Clinical case of the month. An unusual presentation of superior vena cava
      syndrome].
AB  - We report the case of a 48-year-old man who was admitted to our emergency
      department because of a superior vena caval syndrome from which the symptoms
      occurred only during exercise. His past history included an episode of lower limb
      deep venous thrombosis. Because an atrio-ventricular partial block was
      fortuitously evidenced, the patient was submitted to a pacemaker insertion. A few
      years later, the patient suffered from rapid dyspnea on exercise, associated with
      facial cyanosis and systemic hypotension. The exploration by phlebography
      evidenced that the inferior vena cava was completely obstructed. Therefore the
      venous return from the lower part of the body to right heart was obtained through
      hypertrophy of the vena azygos. In addition, the presence of cardiac pacing
      electrodes induced a stenosis at the level of the superior vena cava, just before
      its entrance into the right atrium. Such a venous network accounted for the
      occurrence of a chronic superior vena caval syndrome associated with peripheral
      arterial hypotension during exercise. Treatment consisted of a superior vena
      caval percutaneous transluminal balloon angioplasty followed by a Wallstent
      insertion. This procedure led to a correction of all hemodynamic abnormalities
      responsible for reported pathophysiological limitations to stress.

PMID- 11244798
TI  - [Explosive "thunderclap" headaches: should they be taken seriously?].
AB  - "Thunderclap" headaches are explosive, extremely intense and sometimes associated
      with neurological signs or symptoms. As illustrated by the 3 case histories
      presented here, they are a heterogenous group as far as etiology and prognosis
      are concerned. They may be symptomatic of an intracranial disorder (subarachnoid
      hemorrhage, cerebral venous thrombosis, pituitary apoplexia) or idiopathic
      without any known cause and with a benign, though occasionally recurring, course.
      They can be spontaneous or triggered by Valsalva maneuvers (cough, exertion,
      coitus, ...). In certain cases of so-called "idiopathic" thunderclap headache,
      diffuse, multifocal segmental and reversible vasospasm of cerebral arteries has
      been found on neuroimaging. As headache characteristics are similar in
      symptomatic and benign cases, angio-MRI is recommended when CT-scan and CSF
      examination are normal.

PMID- 11244799
TI  - [Meningococcemia, recrudescence, diagnosis and treatment].
AB  - Meningococcemia is a severe Gram negative septicemia whose mortality may be as
      high as 30%. It occurs more frequently in children but the proportion of
      teenagers is increasing in Belgium. During the past decade, a slow but sustained
      rise in the incidence of this illness has been noted, with a predominance of the
      serogroup B. We describe the symptoms, which often are poor in the early stage,
      the different therapies, most of them being still under investigation, and the
      chemoprophylaxis. Without being alarmist, the diagnosis must be considered in any
      child with cutaneous rash, even atypical and tachycardia.

PMID- 11244800
TI  - [Obesity and hypertension: from physiopathology to treatment].
AB  - Obesity constitutes a problem of major concern in our industrialized countries.
      Overweight is frequently associated with hypertension (50% of hypertensive
      subjects are obese and the prevalence of hypertension in obese patients is twice
      that of the normal population). Both pathologies are major cardiovascular risk
      factors. This review aims at a better understanding of the relationship between
      hypertension and overweight and at giving to the clinicians simple and consistent
      guidelines to treat these two medical entities.

PMID- 11244801
TI  - [Cushing syndromes due to aberrant expression of functional receptors other than
      ACTH. A new organic hypercorticism syndrome entity].
AB  - The diagnosis of Cushing's syndrome remains a challenge in clinical
      endocrinology. Cushing's syndromes are usually classified as dependent or
      independent from ACTH. In the first class are Cushing's disease, the ectopic
      corticotropin syndrome and the rare ectopic CRH syndrome. These ACTH-dependent
      Cushing's syndromes usually present diffusely hyperplastic adrenal glands. In the
      second class, are cortisol producing unilateral adrenocortical adenomas or
      carcinomas. New entities have recently emerged as bilateral adrenal hyperplasia
      not dependent from ACTH; their etiopathogenies are heterogeneous with illicit
      expressions at the adrenal level of functional receptors to various ligands: GIP,
      catecholamines, lutropin... The knowledge of such entities has to be taken into
      consideration in the diagnostic and management of ACTH independent Cushing
      syndromes.

PMID- 11244802
TI  - [Anatomic clinical case. Septic state in a patient with chronic obstructive lung
      disease].
AB  - Invasive aspergillosis is a mycelial infection, associated in 15 to 30% of cases
      with a malignant hemopathy or with other types of cancers. It also constitutes a
      complication induced by high dosage corticotherapy or long term antibiotherapy.
      On the occasion of an autopsy of invasive aspergillosis, we review the anatomo
      clinical entities associated with aspergillus, the etiopathogenic factors and the
      diagnostic difficulties.

PMID- 11244803
TI  - [Surgery of the thymus gland, normal, atrophied or cancerous].
AB  - Thymoma is the most frequently resected mediastinal tumor. Its malignancy is
      related more to macroscopical findings than to microscopical analysis. All
      thymomas should be resected, in order to prevent malignant degeneration.
      Furthermore, for the treatment of myasthenia, several centers recommend resection
      of the thymus, either tumoral (thymoma) or atrophied. Although the role of
      surgery in this regard is controversial, all authors unanimously stress that
      complete resection of all thymic remnants is essential to achieve adequate
      results.

PMID- 11244804
TI  - [Between factoids and facts, between dry skin and rough skin].
AB  - The concept of dry skin as supported by cosmetologists and the layman is
      inadequate. This misnomer entails diverse physiopathologic disorders sharing an
      abnormal and uneven retention of corneocytes. The term xerosis is more
      appropriate to cope with such a definition. Treatments aim at removing the
      corneocytes in excess by opening the corneodesmosomes. A topical supplementation
      in hydrating and emollient agents is beneficial. The application of lipids
      similar to those normally present in the intercellular space also shows efficacy.

PMID- 11244805
TI  - [Extensions of mitral valve repair techniques: surgery for endocarditis and
      valvular tumors].
AB  - Mitral valve repair has demonstrated its superiority over valve replacement.
      Mitral valve repair constitutes the optimal therapeutic option in case of
      degenerative dystrophic, rheumatic, congenital or ischemic mitral valve disease.
      These surgical techniques can also be successfully and advantageously applied in
      case of bacterial endocarditis or tumoral valvular disease. We report a case of
      staphylococcal endocarditis and another case of posterior leaflet fibroelastoma
      to show the place of conservative mitral surgery in these unusual indications.

PMID- 11244806
TI  - [How I investigate...cetain skin disorders by ultrastructural examination].
AB  - Ultrastructural examination of the skin plays an important role in the diagnosis
      of some cutaneous and neurologic diseases such as ichthyoses, inherited
      connective tissue syndromes, non-X histiocytoses, anaplastic tumors, storage
      disorders, mitochondrial and degenerative neuropathies, POEMS, CADASIL.

PMID- 11244807
TI  - [Pharma-clinics. The drug of the month. Dipyridamole-acetylsalicylic acid
      combination (Aggrenox)].
AB  - Aggrenox, launched in Belgium by Boehringer Ingelheim, is a fixed-dose
      combination of extended-release dipyridamole (200 mg) and aspirin (25 mg), two
      antiplatelet agents with different and complementary mechanisms of action. It is
      recommended, twice daily, in the protection against secondary stroke and
      transient ischaemic attacks. The placebo-controlled European study ESPS 2
      (European Stroke Prevention Study 2) demonstrated that the administration of this
      combination was twice as effective as either agent alone in the secondary
      prevention of stroke in patients with prior stroke or transient ischaemic attack.

PMID- 11244808
TI  - [Info-congress. Diabetes research: European diffusion from the Liege univesity].

PMID- 11244809
TI  - [How to manage very elderly patients in the emergency room? Evaluation of 150
      very elderly patients at the Rouen university hospital center].
AB  - OBJECTIVES: There are few data in the literature concerning care provided to very
      elderly subjects referred to emergency care units. The emergency room setting
      would not be particularly adapted to management of this rising population. The
      purpose of our work was to assess the frequency of referral to emergency care
      units, the characteristics of the elderly population, and patient management.
      PATIENTS AND METHODS: One hundred fifty consecutive patients aged over 90 years
      addressed to the emergency unit of the Charles Nicolle hospital in Rouen France
      were studied. These patients were cared for by the medical and surgical teams. We
      recorded, type of referral, hour and reason for admission, degree of handicap and
      residence, gravity at admission using the clinical classification for emergency
      care patients (CCMU), complementary tests performed in the emergency unit,
      duration of stay in the unit and subsequent referral. The characteristics of
      these "very" elderly patients aged over 90 years were compared with those of
      "elderly" patients aged 75-90 years. RESULTS: Over a period of 33 days, the unit
      cared for 4888 patients, including 150 very elderly patients aged over 90 years
      (mean age 92.6 years). Daily, 4.4 patients were referred by a primary care
      physician (76.), mainly between 8 a.m. and 8 p.m. (81.3%). Forty-two percent of
      the patients had a surgical problem. Two-thirds were unable to walk, one-third
      had cognitive disorders, and one-third had urinary incontinence. However, half of
      these very elderly patients lived in a private home. According to the CCMU
      classification, 14.6% of the patients had a life-threatening disorder.
      Complementary tests were ordered for most patients (85%). Mean duration of stay
      in the emergency unit was 3.6 +/- 2.6 days. One quarter of the patients returned
      to their former residence, with a higher percentage among the surgery patients
      (37%) than among the medical patients (14.6%). There was no significant
      difference between the "very elderly" and "elderly" patients in terms of type of
      referral, duration of stay in the unit and subsequent referral. CONCLUSION: "Very
      elderly" patients are frequently addressed to emergency care units by their
      primary care physician. They have severe conditions with major handicaps that
      largely explain their hospitalization. Our results point out possible
      improvements for care in the emergency unit.

PMID- 11244810
TI  - [Respiratory manifestations of hemorrhagic fever with renal syndrome.
      Retrospective study of 129 cases in Champagne-Ardenne and Lorraine].
AB  - OBJECTIVES: The contradiction between airborne transmission of Puumala virus and
      the low rate of airway manifestations reported in hemorrhagic fever with renal
      syndrome (HFRS) caused by this virus led us to conduct this study to check
      whether the incidence of respiratory manifestations may have been underestimated.
      PATIENTS AND METHODS: We retrospectively reviewed 129 consecutive cases of HFRS
      diagnosed between 1983 and 1995 in the eastern France. RESULTS: Clinical
      manifestations of airway involvement and chest X-ray abnormalities were observed
      in 30% and 50% of the patients respectively. Analysing the radiological anomalies
      by serum creatinine level showed that in two-thirds of the cases (33% of all the
      HFRS cases) they were concomitant with acute renal failure and probably related
      to pulmonary edema, and that in one-third (17% of the HFRS cases) they were
      compatible with pneumonia. These cases of pneumonia could correspond to specific
      manifestations of the hantavirus Puumala at the site of penetration. CONCLUSION:
      Although minimally expressive, respiratory manifestations were found to be more
      frequent than expected in hemorrhagic fever with renal syndrome. Incidence may
      have been formerly underestimated.

PMID- 11244811
TI  - [Post-traumatic hypopituitarism].
AB  - BACKGROUND: Post-trauma hypopituitarism is a rare disease, accounting for only 3%
      of all cases of hypopituitarism reported in the literature. CASE REPORT: A 56
      year old woman developed central diabetes insipidus immediately after severe
      cranio-facial trauma. Four years later, she suffered severe asthenia and
      hypoglycemia faintness. The diagnosis of isolated corticotrope insufficiency was
      retained. Magnetic resonance imaging evidenced an intrasellar arachnoidoceae with
      extinction of the posterior pituitary gland's spontaneous hypersignal.
      DISCUSSION: Most cases of post-trauma hypopituitarism occur after high-energy
      head trauma. Hypopituitarism exceptionally involves only one hormone,
      particularly growth hormone. The pathogenesis involves hypothalamic failure more
      often than pituitary gland failure.

PMID- 11244812
TI  - [Tuberculosis tonsillitis and otitis].

PMID- 11244813
TI  - [Febrile pleuropericarditis during valproic acid treatment].

PMID- 11244814
TI  - [Bioavailability of soy isoflavones in supplements for menopausal women].

PMID- 11244815
TI  - [Less salt and a dietetic protocol for reducing blood pressure].

PMID- 11244816
TI  - [A new immunosuppressor: CellCept].

PMID- 11244817
TI  - [Patient information: management in the beginning of the XXIth century].
AB  - The Conseil d'Etat, the supreme jurisdiction on legislative matters in France,
      rendered its decree on January 5, 2000, founding its decision on jurisprudence
      established in 1997 and 1998 by the supreme Court of Appeals. In accordance with
      this decision, physicians have a legal obligation to inform patients of all
      possible risks, including very exceptional risks. The information may be given to
      the patient in any appropriate form. Proof that information was delivered to the
      patient is incumbent upon the physician. When proof of information delivery is
      provided, any injury compensation can only be awarded on the grounds of ill-fate.
      We conducted an objective review of the jurisprudence on patient information and
      report the three basic aspects observed in the current situation in France. In
      application of the Court of Appeals judgments of February 25, 1997 and October
      14, 1997, proof of delivery of information to the patient is incumbent upon the
      physician. The question is whether the physician must retain written documents as
      necessary proof against future claims. The answer to this question is not
      straightforward. A written document is not the only proof accepted by the court
      and could even be of debatable legal value if used inappropriately. The solution
      retained by the Conseil d'Etat is a good example. The real debate concerns the
      information content. It now appears that the physician is required to inform
      his/her patient of all risks susceptible of influencing the patient's decision,
      particularly serious or life-threatening risks, but also, and most certainly,
      risks that in the past have been considered frequent but benign. Finally, the
      judges recall that failure to provide information does not in itself assert the
      physician's civil responsibility, proof of real damage is also needed. But the
      reality of damage (ill-fate) depends on the reality of the choice open to the
      patient had he/she been informed. And the true nature of the choice open to the
      patient is simply the expression of the dispensable or indispensable nature of
      the envisaged act. One could say the old adage primum non nocere is making a
      comeback.

PMID- 11244818
TI  - [Gene transfers to the arterial wall: possible contribution to the treatment of
      Marfan's disease and adjuvant role in concomitant parenteral magnesium therapy].

PMID- 11244819
TI  - [Apoptosis and the thyroid: the Fas pathway].
AB  - THE APOPTOTIC FAS/FAS-L PATHWAY: Represents a major apoptotic pathway and
      involves the specific interaction between a membrane receptor, Fas, harbored by
      the target cell and a membrane ligand, Fas-L, harbored by the cytotoxic cell. FAS
      AND NORMAL THYROID GLAND: Normal thyrocytes express Fas receptor but not its
      ligand. The control of thyroid gland volume results from an equilibrium between
      the trophic action of TSH and thyrocyte apoptosis, which is limited to some
      extent by resistance to Fas activation by producing an inhibitor of the apoptotic
      signal transduction. FAS AND HASHIMOTO'S THYROIDITIS: Aberrant expression of Fas
      L by thyrocytes induces their fratricide apoptosis. Thyroid-infiltrating
      lymphocytes are resistant to apoptosis by overexpressing the antiapoptotic
      protein Bcl2. FAS AND GRAVES' DISEASE: Autoantibody-dependant stimulation of the
      thyrotropin receptor favors goiter formation by reducing thyrocyte apoptosis. It
      induces repression of Fas expression and production of a soluble Fas, whose serum
      levels are correlated with clinical course. FAS AND THYROID CANCER: Tumoral cells
      are resistant to apoptosis by inhibiting the apoptotic signal transduction and
      exert Fas counter-attack by inducing apoptosis of antitumoral lymphocytes.

PMID- 11244820
TI  - [Hypertensive nephropathy: a growing cause of renal insufficiency].
AB  - KIDNEY DISEASE AND HYPERTENSION: Hypertension is increasingly associated to renal
      insufficiency leading to end stage renal damage (ESRD), through several
      mechanisms involving renal vasculature. Ten to 25% of new ESRD patients are now
      categorized as hypertensive nephropathy and vascular renal disease. EPIDEMIOLOGY
      IN FRANCE: Besides the risk of spontaneously evolving atheromatous stenoses of
      renal arteries, the individual risk of ESRD in essential hypertension is
      relatively low, except in selected genetic backgrounds such as black people
      especially in the USA. In long term studies, the risk of ESRD in treated
      hypertensives is between 1.5 and 3% at 15 years, and approximately 3% of French
      hypertensives have plasma creatinine levels above 150 mumol/l. The risk of
      significant creatinine increase is doubled each 20 mmHg increment in diastolic
      BP, but long term studies suggest that the influence of systolic BP is even
      greater. PERSPECTIVES: Animal models have extended our pathophysiological view of
      hypertensive nephropathy, in which renal ischemia and nephron loss will induce
      preglomerular vasodilation and glomerular hypertension. In the future, the
      evaluation of the renal prognosis in essential hypertension could benefit from
      indirect renal hemodynamic explorations, genetic progress, determination of
      microalbuminuria which is the renal probe of a more generalized microvascular
      disease, these indices should be useful to adapt the antihypertensive therapy,
      with the goal of normalizing blood pressure at a lowest albumin excretion rate.

PMID- 11244822
TI  - [Update on tirofiban].

PMID- 11244821
TI  - [Prevention of cardiovascular diseases in type 2 diabetes with aspirin].
AB  - THEORY AND REALITY: Diabetes mellitus is known to be associated with excess
      cardiovascular risk. Prescription of antiplatelet agents such as acetylsalicylic
      acid would thus appear to be warranted. That is the theory, but the reality is
      much different. A review of the literature provides evidence on the use of
      acetylsalicylic acid for primary and secondary preventive care, but conclusions
      are often extrapolated from studies conducted in the general population. EVIDENCE
      OF A BENEFICIAL EFFECT IN DIABETICS: The HOT study, conducted in hypertensive
      patients) demonstrated that acetylsalicylic acid at the dose of 75 mg a day,
      reduced the rate of major cardiovascular events by 15% (p = 0.03) and of
      myocardial infarction by 36% (p = 0.02) with no effect on stroke. In diabetic
      patients (n = 1500), the benefit was even more pronounced. RISKS: The risk of
      bleeding must be balanced against the beneficial cardiovascular effect. Diabetic
      retinopathy is not aggravated by aspirin. The data reported in the literature do
      not however enable any evidenced-based decision on dosing for the diabetic
      population with numerous cardiovascular risks.

PMID- 11244823
TI  - [Anti-Nocardia brasiliensis antibodies in patients with actinomycetoma and their
      clinical usefulness].
AB  - Anti-Nocardia brasiliensis antibodies quantification and its clinical utility was
      confirmed in this study. A protein cellular extract from a N. brasiliensis strain
      named HUJEG-1 and registered at the ATCC # 700358 was used in a western blot
      assay to identify the immunodominant antigens. The protein P24 was selected to
      set up an ELISA test because it exhibit no cross-reaction with sera from
      tuberculosis and leprosy patients. A purified protease was also used as antigen
      in the ELISA test to compare its utility. Sera from N. brasiliensis mycetoma
      persons gave absorbance values above 0.3 when the disease was active using the
      P24 as antigen, these values decreased after patients completed their medical
      treatment. Anti-protease antibodies showed great variation and absorbance values
      similar to the healthy controls. We confirmed the clinical usefulness of the
      ELISA test both in serodiagnosis and in assessing the response to medical
      treatment. This is the first sensitive and specific serologic test for routine
      clinical laboratory.

PMID- 11244824
TI  - [T and B clonal populations in actinic prurigo, a photodermatosis].
AB  - Actinic prurigo (AP) is a chronic photodermatosis in which genetic and
      immunological factors has been implicated in the pathogenesis of the disease.
      This work was designed to investigate the existence of clonal populations of T
      and B lymphocytes in lesions of the labial mucosa and conjunctiva of patients
      with actinic prurigo. Genomic DNA of three patients with actinic prurigo and
      controls were analyzed in Southern blots using DNA molecular probes for the b
      subunit of the T-cell receptor for antigen (TCR beta) and for the heavy chain of
      immunoglobulin genes (lg-JH). Clonal rearrangements of T-cell receptor genes were
      detected in biopsy samples taken from the labial mucosa of two patients and of
      immunoglobulin genes in DNA extracted from the conjunctiva of a different
      patient. The presence of distinct clonal T or B lymphocyte populations in
      patients with actinic prurigo indicates that the immune system may play a
      relevant role in the pathogenesis of the disease.

PMID- 11244825
TI  - [Child health care program in Mexico. Evaluation of the quality of the integrated
      health care given in training centers].
AB  - OBJECTIVE: To assess the quality of the integral care of children under five
      years old (AIMCA) at three first level care units, that without additional
      resources, were selected by the Child Health Care Program (PASN) to function as
      statewide training centers. MATERIAL AND METHODS: Using matching list, structure,
      validated by a consensus of experts and a pilot test, six components of the AIMCA
      were assessed. The study included children under five years old outpatient
      clinic, during a period of a week: on the average 30 at each unit. RESULTS:
      Although there were differences between each health unit, in a high number of
      cases, the score given to each component of the AIMCA was optimum or
      satisfactory. The most relevant deficiencies were those related to the mother's
      training. The assessment allowed for correcting deficiencies in the AIMCA and
      others related with the organization of Training Centers. CONCLUSIONS: It is
      possible to have an AIMCA of good quality, at first level units without
      additional resources. We propose that the mother's training be given mainly by a
      nurse, especially in children with factors of poor prognosis. The methodology
      used can be employed to evaluate the AIMCA periodically at training centers.

PMID- 11244827
TI  - [Brugada's syndrome].

PMID- 11244826
TI  - [Acute myeloblastic leukemia].

PMID- 11244828
TI  - [Parry-Romberg syndrome con glaucoma and pregnancy. First case in the
      literature].

PMID- 11244829
TI  - [Nephrogenic adenoma of the urinary bladder. A lesion that can be confused with
      carcinoma. Report of 4 cases].
AB  - Nephrogenic Adenoma (NA) was first illustrated in 1949 by Davis, who described a
      case he interpreted as a "hamartoma". One year later Friedman and Kuhlenbeck
      described eight further examples in detail and named this lesion nephrogenic
      adenoma. This process is generally accepted to be metaplastic. At cystoscopy and
      on microscopic examination nephrogenic adenoma may simulate a neoplasm. The
      clinical and pathologic findings in four patients are described. The patients
      were two women and two men 20-60 years of age. All of them had a history of some
      inciting injury (infection/calculus). The four cases were initially misdiagnosed
      as a carcinoma. Several features of NA may cause particular diagnostic
      difficulty. Tiny tubules may simulate signet ring cells, the haphazard
      distribution of the tubules or single cell growth may also simulate the
      appearance of an invasive adenocarcinoma. A variety of clinical and pathologic
      differences should enable the distinction of these lesions. Although this is
      occasionally difficult. An emphasis here is placed on the diagnostic problems
      that they may pose for the surgical pathologist. Clinicians and pathologists
      should be aware about this type of lesions in order to avoid pitfalls in the
      diagnosis and treatment of them.

PMID- 11244830
TI  - [Epilepsy: an incapacitating disease? Propitiatory topic for a free program for
      epileptics].
AB  - The facts and causes for the margination of people that suffer epilepsy, their
      problems regards social adaptation and even familiar troubles, all together
      circumstances that they are carrying since ever in the times until nowadays, are
      reviewed on the basis of the social and historical aspects and the evolution of
      ideas regards epileptology. It is stated why such opinions should be reconsidered
      and instead of which, to divulge appropriate arguments to realize that those
      persons should enjoy general acceptance and achieve the most adequate
      development.

PMID- 11244831
TI  - [Physicians and surgeons in the Constituent Congress (1856-1857) and the Reform
      War (1858-1860)].
AB  - A small but selected group of physicians and surgeons took part in the
      Constituent Congress elaborating the Mexican Constitution of 1857. Among them was
      doctor Valentin Gomez Farias, leader of the liberal party. He presided at the
      oath of the constitution. Another prominent number of the said Congress was
      doctor Jose Maria Mata, who, in the session of August 5th. 1856, defended
      vehemently the article 15 of the project of constitution in favor of the freedom
      of worship. Doctor Isidoro Olvera is also worthy of remembrance, because on
      August 7th. of the same year presented an extensive outline of organic law
      concerning the right of "ownership". When the conservative revolt started on
      December 17th. 1857, doctor Olvera at the time president of the Chamber of
      Deputies was imprisoned with Benito Juarez, president of the Supreme Court of
      Justice, and three more representatives. During the civil war between
      conservative and liberal partisans, which began on January 19th. 1858, several
      distinguished physicians and surgeons, as well as medical students, were victims
      of the sectarian hatred. The example of these pupils of Aesculapius, who were
      victims of their vocation and of their mission, should always be kept in mind.

PMID- 11244832
TI  - [First anesthesia with ether in Aguascatientes, Mexico].

PMID- 11244833
TI  - [Persistent left superior vena cava. Incidental finding with helicoid computed
      tomography].

PMID- 11244834
TI  - [A new predisposition to diabetes type 2 gene].

PMID- 11244835
TI  - [Endoscopic diagnosis of tumors of Vater's ampulla].
AB  - The diagnosis of ampulla of Vater tumors is complex due to the proximity of other
      anatomical structures that are the originating sites of tumors with different
      natural histories, treatment and prognosis. A retrospective study of 65
      consecutive patients with conclusive ampulla of Vater tumor diagnosis from
      January 1994 to April 1998 was conducted. Icterus was the principal symptom in
      92%. In 34/65 patients on whom ultrasound or CT scan were performed, nearly half
      showed only dilation in the bile ducts, an ampullar tumor was suspected in six,
      in another six, pancreatic tumor was suspected and then discarded, and seven had
      no specific findings. Endoscopic imaging discovered the tumor in all of the
      cases, but the biopsy was diagnostic in only 84.6%: forty-eight carcinomas were
      discovered in addition to six adenomas (two with carcinoma and one with
      dysplasia) and one lymphoma. A diagnosis was arrived at in ten patients with
      negative biopsies through other means. Surgeries uncovered two carcinoids with
      endoscopic diagnosis of carcinoma. It was concluded that endoscopy is a good
      diagnostic method that allows palliation; however, it requires a perfecting
      process such as endoluminal ultrasound, specially if, taking into consideration
      the elevated morbimortality involved in pancreatoduodenectomies, conservative
      treatment is sought.

PMID- 11244836
TI  - [Osteoporosis: When should bone densitometry be requested?].

PMID- 11244837
TI  - [Tuberculosis in Mexico, an old public health debt].

PMID- 11244838
TI  - [Clinico-pathologic exercise Gaceta Medica de Mexico volume 136, No. 5 May-June
      2000].

PMID- 11244839
TI  - Genomics and new technologies as catalysts for change in the drug discovery
      paradigm.
AB  - The pharmaceutical industry is faced with unprecedented opportunities emerging
      from genomic sequencing. In parallel, many new technologies in the areas of
      informatics, molecular biology, combinatorial chemistry, and high throughput
      screening offer new strategies to deal with this mass of information and
      translate it into tangible treatments for human diseases. Increasing pressures to
      control prices counterbalances these opportunities. This paradox will require a
      rethinking of how the industry approaches drug discovery and development, and new
      paradigms will need to be explored to ensure these opportunities can realized for
      human health care in a timely and cost-effective manner.

PMID- 11244840
TI  - Genetic advances and legal institutions.

PMID- 11244841
TI  - Genomics: launching a revolution in medicine.

PMID- 11244842
TI  - Genomics and degenerative diseases of the nervous system.

PMID- 11244843
TI  - The food wars: a potential peace.

PMID- 11244844
TI  - The challenge of making laws on the shifting terrain of science.

PMID- 11244845
TI  - The Human Genome Project: interaction of the physical sciences with biology.

PMID- 11244846
TI  - [Theoretical and experimental rationale of the duration of a stimulating impulse
      for endogenous electrostimulators of the gastrointestinal system].
AB  - The paper presents data obtained from processing experimental findings of the
      electric conductivity of the actual media of the human gastrointestinal tract
      (GIT) as pH and temperature functions. Based on these data and experimentally
      derived values of electrode capacities of self-contained GIT electrostimulators
      in the real digestive tract, the authors calculated the values of stimulating
      pulse discharges. It was concluded that the discharge accumulated in the
      electrode containers is quite sufficient for stimulation of intestinal smooth
      muscle cells by using the purely capacity component of a stimulating pulse, It
      was shown that in this case the stimulating pulse was to be 0.8-1.2 msec.

PMID- 11244847
TI  - [A procedure of detecting and measuring pelvic bone displacement by an original
      orthopedic grid-plate].
AB  - An original orthopedic grid plate made of transparent organic glass with
      horizontal and vertical lines marked on it, which are projected on the most
      important diagnostic parts of the pelvic ring when the plate is applied to the X
      ray film of the latter. Asymmetry detected in different portions of the pelvic
      ring and its values expressed in millimeters was successful in detecting
      insidious and hardly noticeable ring displacements and in measuring the latter.

PMID- 11244849
TI  - [Evaluation of physical factors of electrosurgical effects as bases in designing
      automated electrosurgical devices].
AB  - The paper shows how to study the physical factors of electrophysical exposure,
      such as an energetic factor caused by high concentrations of high-frequency
      current and an electromagnetic factor caused by the presence if an electric
      field, and other concomitant factors in order to outline ways of designing
      automatic electrosurgical apparatuses operating more effectively in different
      lines of surgery.

PMID- 11244848
TI  - [Improvement in the technology of washing erythrocyte-containing transfusion
      media].
AB  - A new device for preparing washed red cell components was proposed by the Sintez
      Co., Kurgan. The disposable containers were evaluated at the Center of Blood and
      Tissues, Military Medical Academy. The new system was found to be more effective,
      time-saving, cost-effective and decreased the risk of infectious complications as
      compared to the traditional methods for washing red cell components. Thus, the
      new device can be recommended for wide use in transfusion medicine.

PMID- 11244850
TI  - [Automated system of phasing pulse-wave electrosurgical effects].
AB  - The authors propose an automatic system for creating stable hemostasis for an
      electrosurgical apparatus, which includes a scheme to assess a pulse wave and its
      maximum and minimum values at the site of surgical exposure, an electrosurgical
      apparatus, and a scheme to obtain data on the values of the pulse wave in a given
      patient.

PMID- 11244851
TI  - [Interactive determination of the parameters of mathematical models in planning
      radiotherapy of malignant tumors. 3. Method of local adjustment of the parameters
      of mathematical models (examples of application)].
AB  - To increase the accuracy of calculation of tolerance doses of the likelihood of
      radiation-induced complications in normal organs and tissues by using
      mathematical models, the author has developed a method for local mathematical
      model parameter adjustment (LMMPA) which included analysis of the structure of a
      mathematical model, systematization of clinical information and its goal-oriented
      use to determine the parameters of a model. The necessity of developing the LMMPA
      method stemmed from the complexity of the body exposed to radiation a system and
      from the quest for taking into account the impact of the system on the values of
      mathematical models. LMMPA may be regarded as the extension of determination of
      the parameters of mathematical models or as the interactive determination of
      their parameters that describing radiation exposures of complex biological
      systems. Different aspects of using of LMMPA are indicated how to apply it to the
      determination of tolerance doses for connective tissue, lung tissue, and the
      brain by using the Ellis and LQ models. The extended LMMPA is shown how to
      determine the parameters of a mathematical models for calculation of the
      likelihood of radiation-induced complications in the lung tissue.

PMID- 11244852
TI  - [A program package of collection and mathematical processing of ECG data on the
      basis of COM architecture].
AB  - The paper deals with general questions of the Component Object Model (COM)
      architecture for ECG software applications. Here their common structure is
      presented, the benefits and constraints of component-based applications are
      considered. Being a component model, COM allows one to build any application the
      functionally complete modules. Each module is developed by the particular
      protocol that gives developers a possibility to provide effective
      interoperability between such components. The separate part of the article is
      devoted to reliability and performance issues of the component-based ECG
      applications. The approach described in this article permits one to solve a
      number of problems facing medical software developers by using the effective and
      flexible component architecture. As implementation of the discussed architecture,
      a software ECG system being developed by a team of authors is presented.

PMID- 11244853
TI  - [A view on training clinical engineers].
AB  - Experience in using a new developed method for training engineers who get an
      additional secondary medical education is considered. The results of interaction
      of the N. E. Bauman Moscow State Engineering University and Moscow Medical
      College No. 1 in applying the method are presented. The advantages and prospects
      of the combined training method are discussed. Priority problems of Russian
      public health service facing postgraduate who get double education are revealed.

PMID- 11244855
TI  - [Use of systems approach to solving regional problems of renewal of the stock of
      ultrasound scanners (the case of the Smolensk Region)].
AB  - The Smolensk Region (Russian Federation) was used to assess how ultrasound
      diagnosis is made in the therapeutical and prophylactic institutions.
      Requirements for the diagnosis are worded in terms of regional, organizational,
      and other features. At the same time the paper gives main criteria for assessing
      the obsolescence of equipment; data on the level of organization of service; a
      share of brands of equipment; and characteristics of manufacturers in the
      ultrasound equipment market of the Smolensk Region.

PMID- 11244854
TI  - [Specific features of organizing mammography services].
AB  - The organizational features of general-purpose mammographic room, as well as
      specialized and X-ray operating room are outlined.

PMID- 11244856
TI  - [Manufacture of electrocardiographs in the Russian Federation].
AB  - The paper considers the state of Russian electrographic technology in Russia and
      gives examples of its electrocardiographic apparatuses, among which there are
      electrocardiographs in common use and cardiac complexes that have extended
      functional capacities.

PMID- 11244857
TI  - [Hardware support of volumetric calibration of impedance pneumogram].
AB  - Failure to determine volumetric lung ventilation parameters is a limitation of
      impedance pneumography. The purpose of the study is to develop hardware and
      software for volumetric calibration of an impedance pneumograph and to assess the
      errors of methods in the measurement of breathing volume in healthy individuals
      and in patients with bronchial asthma (BA). A personal computer-based Respicard
      1.2 hardware complex is described. The improved calibrating algorithm that
      ensures a 1.5-fold decrease in errors. The calibration coefficient was 1.41 +/-
      0.13 l/ohm in healthy individuals and 1.13 +/- 0.07 l/ohm in patients with
      bronchial asthma. The relative errors of breathing volume measurement was 6.1 +/-
      0.6 and 12.0 +/- 1.0%, respectively (p < 0.01). It has been concluded that it is
      expedient to use the developed hardware complex for monitoring the respiratory
      pattern.

PMID- 11244858
TI  - [Use of US-contrast media in the diagnosis of carotid artery stenosis].
AB  - With the advent of ultrasound diagnostic devices that provide a possibility of
      colored mapping, regimes of energy Doppler regimens, and procedures of second
      harmonic, conditions for using ultrasound contrast agents occurred. The drug
      Levovist was used during carotid Doppler study in 16 patients in whom primary
      vascular scanning was of poor quality. The use of Levovist improved the accuracy
      of diagnosing the degree of arterial stenosis from 40 to 95%. Thus, the use of
      ultrasound contrast agents in Doppler ultrasound of carotids makes it possible to
      specify the degree of stenosis, to differentiate arterial subocclusion and
      occlusion, to visualize minor vessels with low blood velocity.

PMID- 11244859
TI  - [Use of photo-ultrasound technology in the treatment of infected wounds].
AB  - The paper details three of the technologies used in the treatment of infected
      wounds (ultrasound, photodynamic, photomatrix ones) with emphasis on the authors'
      developed combined photo ultrasound technique. It presents the results of
      clinical application of these technologies, discusses its capacities,
      limitations, and prospects alone and in combination. The high efficiency of
      combined exposure--the photo ultrasound method--is shown.

PMID- 11244860
TI  - Haematology and plasma biochemistry of Stamboek pre-pubertal gilts in Italy:
      reference values.
AB  - Blood samples were taken between February and April from 105 healthy Stamboek pre
      pubertal gilts, aged 1-3 months, which were housed at a modern pig farm in
      northern Italy. The blood was analysed for nine haematological and nine selected
      haematochemical variables by means of automated and semiautomated blood analysis
      apparatus. After detection and rejection of outliers, the data were submitted to
      reference limits evaluation, also taking into account the limits for the red
      blood cell volume histogram as the anisocytosis index. Some haematological
      reference values deal with previously published data; in the haematochemical
      parameters, several discrepancies between evaluated limits and existing reference
      limits were noted, mainly for aspartate aminotransferase, alanine
      aminotransferase and lactate dehydrogenase levels and total protein
      concentration. The results confirm the relevance of age in determining blood
      reference intervals and that 'normal' values should be determined by each
      laboratory, taking into account the age of subjects, the sample size and methods
      of analysis.

PMID- 11244861
TI  - Course of epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I)
      in mammary secretions of the goat during end-pregnancy and early lactation.
AB  - The epidermal growth factor (EGF) plays a crucial role in mammogenesis in many
      species. In ruminants, studies are limited, as EGF does not occur in peripheral
      plasma and specific analytical systems do not exist. Therefore a heterologous
      radioimmunoassay based on rhEGF was set up to monitor EGF in mammary gland
      secretions from goats during end-pregnancy and early lactation. IGF-I was
      measured with an established radioimmunoassay. Samples were collected from 13
      goats for 25 days ante-partum and 25 days post-partum. Mammary gland secretions
      were obtained ante-partum by removing a small amount of the udder secretions
      (control half) or milking (stimulated half). Post-partum normal milk samples were
      collected. Blood samples were drawn by jugular venipuncture for the same period.
      EGF was found to occur in different molecular weight forms in the mammary glands.
      For routine measurements these proteins were extracted with acetone and not
      further separated. IGF-I and EGF concentrations in mammary secretions and
      similarly IGF-I in blood were high ante-partum and decreased slightly towards
      birth. IGF-I but not EGF is found in the peripheral plasma. Whereas IGF-I
      concentrations in blood were quite constant post-partum, IGF-I and EGF dropped in
      mammary secretions close to the detection limits. The decrease was more
      pronounced in the stimulated half than in the control half. The data support a
      synergistic role for EGF and IGF-I for mammogenesis. Both factors are further
      influenced by the milking stimulus and thus the functional state of the udder.

PMID- 11244862
TI  - Differential electrocardiographic study on Iberica and Duroc breeds of pig during
      physical maturation.
AB  - Sequential electrocardiograms were taken of 50 pigs (25 Iberica and 25 Duroc),
      from the ages of 5 days to 205 days. The records were analysed to establish the
      normal values of the different electrocardiographic intervals (RR, QRS, QT, TQ
      and ST intervals), the diastole/systole quotient and heart score in the first 7
      months of life, as well as age-related electrocardiographic variations. In
      addition, it was intended to determine which of these two breeds showed the
      greater heart recovery capacity. Finally, positive or negative correlations
      between the RR interval and the electrocardiographic incidents studied were
      analysed. The mean values obtained for the electrocardiographic parameters were
      similar in the two breeds and increased with their physical maturity. Analysis of
      the correlation between the duration of the heart cycle and the different
      electrocardiographic incidents showed a positive and significant correlation, the
      r-values being higher for the RR interval-TQ interval correlation. There was very
      little correlation between RR interval and heart score in Duroc pigs and
      practically no correlation between the RR interval and the QRS interval in either
      breed.

PMID- 11244863
TI  - Evaluation of a transportable [Ca++] and pH analyser and of the impact of
      different anticoagulants and sampling sites in cattle.
AB  - A mobile, hand-held ionized calcium and pH analyser, the IRMA (Immediate Response
      Mobile Analyser) SL (Diametrics Medical Inc. St. Paul, MN, USA), was evaluated
      and results interpreted with help from data derived on biological variation in
      five dry cows. The maximum allowable analytical imprecision (CMAX) was estimated
      as 1.33% for [Ca++] and 0.12% for pH; the maximal allowable analytical inaccuracy
      (BMAX) was estimated to be 1.82% ([Ca++]) and 0.09% (pH), and the maximum
      allowable difference between two methods (MAXDIFF) was calculated as 0.89%
      ([Ca++]) and 0.08% (pH). These values were compared with the coefficient of
      variation obtained by calculation from analysis results in blood samples obtained
      from 51 cows, heifers and calves. The between-cow coefficient of variation (CV),
      within-cow CV, critical difference (two-sided) and index of individuality were
      estimated as 4.77, 2.66 and 14.29%, and 1.08 for [Ca++] analysis. For pH
      measurements, values of 0.12, 0.24 and 0.96% and 2.95 were estimated. The number
      of samples required to determine the true value of either [Ca++] or pH in an
      individual cow was 5 and 1, respectively. Further, it was observed that, in
      investigations of blood Ca++ and blood pH in cattle, neither the use of
      electrolyte-balanced syringes interchangeable with sodium-heparin vacutainer nor
      the use of different blood sampling sites was to be recommended. IRMA SL did not
      correlate significantly with the chosen reference analyser (Stat Profile 5
      Analyser; Nova Biomedical, Waltham, MA) with regard to plasma [Ca++] analyses
      (correlation coefficient r = -0.24, P = 0.22). However, a significant correlation
      coefficient (r = 0.63, P < 0.01) was found between analyses of pH performed on
      IRMA SL and Stat Profile 5 Analyser. Analysis on IRMA SL was very easy to
      perform. It could be a very useful aid in veterinary clinical practice, when
      determination of plasma pH in cattle is needed. The analyser should not yet be
      applied uncritically with respect to [Ca++] analyses in cattle.

PMID- 11244864
TI  - Production of reactive oxygen species in neutrophils after repeated bouts of
      exercise in standardbred trotters.
AB  - Six trained Standardbred trotters exercised on a  racetrack on 2 days with a 3
      day interval. On both exercise days the horses trotted three different exercise
      bouts with increasing intensity with 60-min intervals. Exercise-induced stress
      was manifested as leucocytosis, an increase in the neutrophil:lymphocyte (N:L)
      ratio, and increased capacity to produce reactive oxygen species in the
      peripheral blood as indicated by an increase in whole blood chemiluminescence.
      The leucocytosis was mainly due to neutrophilia, which lasted for 6 h. Production
      of reactive oxygen species per single neutrophil showed no significant change
      during a day of exercise, but was lower on the second exercise day. The cortisol
      concentrations and N:L ratio, used as indicators of stress, behaved differently:
      Cortisol did not change significantly after exercise, whereas the N:L ratio
      increased. These results suggest that in trained horses, the N:L ratio is a
      sensitive indicator of stress of short duration, and an attenuated N:L response
      can be taken as an indicator of adaptation to exercise stress.

PMID- 11244865
TI  - Pathological and biochemical studies on experimental hypothyroidism in growing
      lambs.
AB  - Secondary iodine deficiency was experimentally produced in growing male lambs by
      oral administration of 50 mg/kg bodyweight of Thiourea daily for 3.5 months. At
      the end of the experiment the animals became weak, emaciated, anaemic,
      significantly reduced in body weight with facial oedema and alopecia at thigh,
      legs and abdomen. The clinical analysis showed significant reduction in
      erythrocyte and leucocyte numbers and in levels of triiodothyronine and
      testosterone at the end of the experiment. The histopathological picture of the
      thyroid gland revealed hyperplasia of the follicle-lining epithelial cells which
      project into the lumen. The lumens of the follicles are devoid of colloid. The
      testes showed ill-developed small, empty seminiferous tubulcs. In the liver, the
      hepatocytes showed degeneration and vacuolation with proliferation of Kupffer
      cells, which contain haemosiderin pigment. The kidney showed glomerular lipidosis
      with accumulation of haemosiderin pigment in the cytoplasm of the renal tubules.
      Hyperkeratosis of the epidermis associated with excessive keratin formation
      within the hair follicles was detected. In conclusion, deficiency of iodine
      causes hypothyroidism which leads to retardation of growth, reduced wool
      production and interferes with sexual maturity of growing male lambs.

PMID- 11244866
TI  - Effect of intramammary infusion of tumour necrosis factor-alpha on milk protein
      composition and induction of acute-phase protein in the lactating cow.
AB  - The present study was designed to evaluate the effects of tumour necrosis factor
      alpha (TNF-alpha) on lactating bovine mammary functions such as milk protein
      secretion and the integrity of the milk-blood barrier. The effect on the
      induction of the systemic inflammatory response was also examined using
      concentrations of serum haptoglobin (Hp), a major inflammatory acute-phase
      protein, as an index. One hundred micrograms per mammary gland of recombinant
      bovine (rBo) TNF-alpha or placebo saline was individually infused into a rear
      mammary gland of each of four lactating cows, and milk and blood samples were
      collected before and 4, 8, 24, 32, 48, 96 and 168 h after infusion. In the rBoTNF
      alpha-infused gland, increases of somatic cell counts were observed at 4-48 h.
      Although concentrations of total milk protein were not changed, compositions of
      milk proteins varied following rBoTNF-alpha infusion. Concentrations of caseins,
      alpha-lactalbumin and beta-lactoglobulin were significantly decreased at 4 and 8
      h. Lactoferrin concentrations were significantly increased at 4 h. Significant
      infiltrations of serum albumin, immunoglobulin G1 (IgG1) and IgG2 were observed
      at 4 and 8 h. Elevations of the serum concentration of Hp were detected at 8-32
      h, but were very small in comparison with those reported in inflammatory
      diseases. Changes in rectal temperature and white blood cell counts were not
      significant. These results show that single rBoTNF-alpha infusion into the
      lactating mammary gland suppresses the lactogenic function of the gland and
      influences the function of the milk-blood barrier, with little effect on the
      generalized inflammatory response.

PMID- 11244867
TI  - Weaning of piglets. Effects of an exposure to a pathogenic strain of Escherichia
      coli.
AB  - The influence of weaning on day 32 and a simultaneous challenge with a pathogenic
      strain of Escherichia coli was studied in eight piglets. Another nine weaned but
      non-infected piglets were used as controls. The distribution of peripheral blood
      mononuclear cells (PBMC) into subpopulations, as well as their response when
      stimulated in vitro by pokeweed mitogen, changed in a similar manner during post
      weaning in both groups. In contrast, superior responses were recorded for PBMC
      collected from the challenged pigs when stimulated in vitro with concanavalin A
      and with a heat-inactivated extract of the E. coli strain used for infection,
      respectively. Despite a successful colonization of the challenge strain, no
      clinical signs of disease were recorded. Nor did the daily weight gain or the
      number of E. coli, enterococci, or Clostridium perfringens excreted per gram of
      faeces differ between the groups. However, the weaning induced a marked decrease
      in the diversity of coliforms in individual piglets, which announced a reduced
      colonization resistance of that flora. Also, a decreased homogeneity between
      coliform floras of different piglets was observed following weaning. The
      decreased homogeneity indicated that different strains of E. coli were
      predominant in different animals, which may in turn facilitate the spread of
      pathogenic strains. The enteric changes were more pronounced and lasted longer in
      infected animals. Still, the influence of a sole pathogenic strain of E. coli was
      not enough to induce post-weaning diarrhoea.

PMID- 11244868
TI  - Frequent exposure of mice to crude Brucella abortus proteins down-regulates
      immune response.
AB  - Mice repeatedly immunized via the intraperitoneal route with a Brucella abortus
      antigen lost their ability to develop a strong in vitro lymphoproliferative
      response. This result correlates with a decreased tendency of the lymphoid
      population to produce interferon-gamma when stimulated in culture with the
      immunizing antigen. With respect to the humoral response, as the number of
      immunizations increased, the animals produced more specific immunoglobulin M and
      immunoglobulin G1 antibodies. It is postulated that the long-term exposure of an
      animal to Brucella antigen changes the nature of the immune response from a T
      cell-mediated response to a humoral response favouring the establishment of the
      disease.

PMID- 11244869
TI  - Evaluation of two commercial systems and a new identification scheme based on
      solid substrates for identifying coagulase-negative staphylococci from bovine
      mastitis.
AB  - Coagulase-negative staphylococci (CNS), mainly isolated from bovine mastitis (n =
      89, representing 11 different species), were used to evaluate two commercial
      identification systems: ID 32 Staph and Staph-Zym. The level of agreement between
      the ID 32 Staph and Staph-Zym systems and conventional methods was 77 and 94%,
      respectively. An alternative method, based on solid biochemical substrates, is
      also presented. This can be used for identifying novobiocin-sensitive CNS strains
      from bovine mastitis.

PMID- 11244870
TI  - Experimental infection of chamois (Rupicapra pyrenaica parva) with Sarcoptes
      scabiei derived from naturally infected goats.
AB  - Two chamois (Rupicapra pyrenaica parva) out of a group of three were
      experimentally infected with Sarcoptes scabiei derived from a naturally infected
      domestic goat. One of the chamois presented the first clinical manifestations
      (papules and desquamation) at 7 days post-infection, after 22 days crusts and
      alopecia appeared and after 41 days pruritus. The other chamois presented
      desquamation after 15 days and papules after 21 days and crusts and alopecia
      after 31 days. All these clinical manifestations continued to spread and when the
      animals were treated at 84 days post-infection, pruritus, papules and crusts were
      first to disappear, there being no evidence of their presence at 99 days post
      infection, when the second treatment dose was applied. The desquamation and
      alopecia disappeared at 114 days post-infection, by which stage both animals were
      considered to have been cured. The results of the skin scraping was negative in
      both chamois until 54 days post-infection and it became negative again after 84
      days, when the first treatment dose was applied. Biopsies showed different levels
      of hyperkeratosis and a marked epidermic hyperplasia with formation of small
      crusts. Superficial epidermis presented marked vasodilatation and also
      infiltrated inflammation. None of the biopsies carried out showed the presence of
      parasites. The non-infected chamois, which was kept in the same compound as the
      other two, did not present any clinical manifestations compatible with infection
      by S. scabiei throughout the entire period of the experiment.

PMID- 11244871
TI  - Antigenic characterization of bovine viral diarrhoea virus isolates from Spain
      with a panel of monoclonal antibodies.
AB  - A group of 47 bovine viral diarrhoea virus (BVDV) strains isolated from a variety
      of bovine tissues from eight different geographical areas of Spain and two BVDV
      strains isolated from a cell line were characterized antigenically with a panel
      of 23 monoclonal antibodies (mAbs). The mAbs were directed at one of three viral
      proteins: E2, Erns and NS2-3. A peroxidase-linked assay was used to test the mAbs
      for reactivity against infected cell monolayers. The data were analysed by two
      computational methods: the Antigenic Distance Program (MAP) and the Phylogeny
      Inference Package (PHYLIP), and compared with those obtained previously using the
      same mAbs with other pestiviruses, including reference strains and UK field
      isolates. All the Spanish field strains studied appeared to be broadly similar to
      reference strains of BVDV and were included in the subgroup of classical BVDV,
      meanwhile the two strains isolated from a cell line were included in the subgroup
      of atypical pestiviruses.

PMID- 11244872
TI  - Studies of the phenomenon of host adaptation in Salmonella.
AB  - To study the phenomenon of host adaptation in Salmonella, a mathematical model
      has been developed which permits a definition and experimental investigation of
      the specific interaction between the adapted serovar and the adequate host. After
      experimental infection using a mixture of equal parts of two Salmonella strains,
      A and B, the bacterial concentrations CA and CB were determined in the organs of
      the animals infected. If an animal of species a and an animal of species b are
      infected with the same mixture of strain A adapted to a and strain B adapted to
      b, an expression: log10Qab = log10CaA + log10CbB - log10CaB - log10CbA may be
      calculated which describes the influence of the specific serovar-host interaction
      on the dynamics of the bacterial count. The variable Qab was determined using
      four Salmonella dublin, four Salmonella choleraesuis and five Salmonella
      gallinarum/pullorum strains in a total of 63 pairs of different hosts (calf and
      pig, calf and chicken, or pig and chicken). On this basis, the following
      statements can be made. The epidemiologically defined host adaptation of
      Salmonellas is accompanied by a specific agent-host interaction between the
      adapted serovar and adequate host. It promotes adherence and spreading of the
      agent in the adequate host. The effect was particularly expressed on day 3 post
      infection and could be detected both in the lumen of the anterior sections of the
      intestine and in the intestinal lymph nodes and the liver. In part, the host
      independent strain characteristics had a greater influence than the specific
      serovar-host interaction on the dynamics of the bacterial count. Strains of non
      adapted serovars may thus result in a more intense colonization and invasion of
      the host than simultaneously administered bacteria of a serovar which is adapted
      to the respective host. The effects of a specific serovar-host interaction on
      colonization of and spreading in the host should be considered only as a
      component which contributes to the phenomenon of host adaptation.

PMID- 11244873
TI  - [Specialist network "Inflammatory-rheumatic systemic diseases." Developmental
      perspectives for rheumatology in Germany].

PMID- 11244874
TI  - [Immunogenetics of inflammatory rheumatic diseases].

PMID- 11244875
TI  - [Immunopathogenetic hypotheses in inflammatory rheumatic diseases].

PMID- 11244876
TI  - [Epidemiological and public health aspects of inflammatory rheumatic systemic
      diseases].

PMID- 11244877
TI  - [Therapy of inflammatory rheumatic diseases: from current practice standards to
      future].

PMID- 11244878
TI  - [New findings regarding the clinical outcome of rheumatic diseases].

PMID- 11244880
TI  - [Echocardiography: indications and diagnostic value].

PMID- 11244881
TI  - [Initial manifestation of diabetes type 1 with anemia, hyperparathyroidism, and
      abdominal lymphadenitis].

PMID- 11244882
TI  - [Generalized calcinosis cutis; search for the causal autoimmune disease].

PMID- 11244883
TI  - [Vasopeptidase inhibition. A new mechanism of action for the treatment of
      hypertension and cardiac insufficiency].

PMID- 11244884
TI  - [Endoscopy within the network of diagnostic imaging].

PMID- 11244885
TI  - [PRISMS study. Interferon beta-1a therapy in relapsing-remitting multiple
      sclerosis].

PMID- 11244886
TI  - [Psychosomatic dermatology in Germany: a survey of 69 dermatologic clinics].
AB  - BACKGROUND AND OBJECTIVE: A questionnaire study of German dermatological clinics
      was designed to show the situation and development of psychosomatic dermatology
      10 years after a similar study. PATIENTS/METHODS: A questionnaire was sent to 170
      dermatological clinics. 76 were send back; 69 of them (40.6%) were evaluable. The
      questionnaires were mostly answered by the heads of the dermatological clinics
      (38/69 = 55.1%). RESULTS: Nearly 85% of the dermatological clinics answered that
      they take psychosomatic aspects into consideration in the therapy. 5.1% of the
      dermatologists working in clinics have additional psychotherapeutic
      certification. The improvement of coping behaviour seems to be the main goal of
      psychosomatic interventions. The importance of psychic factors increased in the
      last 10 years in comparison to a former study in regard to most of the
      dermatological diseases. CONCLUSIONS: Psychosomatic aspects seem to be an
      obligatory part of inpatient dermatological therapy. The frequency of some
      diseases was underestimated in comparison with results from literature.

PMID- 11244887
TI  - [Prurigo pigmentosa].
AB  - Prurigo pigmentosa is rather frequently observed in Japan. By contrast, this skin
      disease has so far rarely been reported in German speaking countries or elsewhere
      in Europe. In order to make the European dermatologists familiar with this
      peculiar skin disease, the epidemiological features as well as the clinical and
      histopathological findings are reviewed. The disease can be discriminated from
      prurigo simplex subacuta by the typical reticular hyperpigmentation, by the
      sparing of arms and legs and by the response to treatment with dapsone or
      minocycline. Additional differential diagnostic possibilities include lichen
      amyloidosus and confluent and reticulate papillomatosis of Gougerot-Carteaud.
      Diabetes or malnutrition may represent etiological factors. Because this unusual
      skin disease may also occur in Europe, dermatologists here should include prurigo
      pigmentosa in the differential diagnosis of acquired pigmentary disorders.

PMID- 11244889
TI  - [Treatment of hemangiomas in infancy and childhood with the flash lamp-pumped dye
      laser: cutaneous versus mixed cutaneous-subcutaneous hemangiomas].
AB  - The efficacy of flashlamp-pumped pulsed dye laser therapy at 585 nm for cutaneous
      and mixed hemangiomas was assessed in 165 children with 225 separate hemangiomas
      were treated in 332 sittings over 2.5 years. The patients were divided into three
      groups: 100 patients with 153 flat cutaneous hemangiomas, 47 patients with 54
      mixed cutaneous-subcutaneous hemangiomas and 18 patients with 18 superficial
      hemangiomas in the involution phase. In the first group of 100 patients with 153
      flat cutaneous hemangiomas, 52 (34%) of the lesions showed total lightening. 21
      of the 153 lesions showed proliferation of the subcutaneous component, although
      these lesions were flat at first presentation. Of the 54 mixed hemangiomas, 33
      (61%) had continued proliferation of the subcutaneous component. The cutaneous
      component responded to therapy in 21 (39%) hemangiomas while the subcutaneous
      component of the mixed hemangiomas remained unchanged. No lesions in this group
      involuted completely and therapy was discontinued because of a relatively poor
      response to therapy. 12 (67%) of the 18 patients with superficial hemangiomas in
      the involution phase had excellent results, and 6 (33%) had good results. We
      conclude that treatment with the flashlamp-pumped pulsed dye laser is very
      effective and may be the treatment of choice for selected hemangiomas, especially
      cutaneous hemangiomas at sites of potential functional impairment (hands or feet,
      anogenital-region), and on the face. Furthermore, laser therapy should be
      initiated as early as possible, even in the first days or weeks of life, when the
      hemangioma is flat, to prevent enlargement, promote involution, or eliminate
      these vascular lesions.

PMID- 11244888
TI  - [Benign melanosis of the lip. Treatment with the Q-switched ruby laser].
AB  - BACKGROUND AND OBJECTIVE: Benign melanosis of the lip represents a cosmetic
      problem for many of those who are afflicted. It responds well to therapy with Q
      switched lasers. The value of previous studies has been limited by small numbers
      of cases or short follow-up times. PATIENTS/METHODS: In a retrospective study 9
      patients were treated by the Q-switched ruby laser (694 nm, pulse duration 25-40
      ns, spot size 4 mm, energy density 10 J/cm2) in the period from 5/94 to 10/99.
      The benignity of the lip melanosis was determined dermatoscopically. In one case,
      the diagnosis was also confirmed histologically by a punch biopsy. The follow-up
      time was between 6 months and 5 1/2 years. RESULTS: In 3 cases a complete
      clearance of the melanosis was achieved after one session, while in 6 patients a
      second treatment was required. There were no recurrences. Scars or pigment
      alterations were likewise not observed. CONCLUSIONS: The treatment of benign
      melanosis of the lip with the Q-switched ruby laser is an elegant and safe method
      with excellent cosmetic results.

PMID- 11244890
TI  - [Imiquimod: a new treatment possibility in bowenoid papulosis?].
AB  - Bowenoid papulosis is a highly characteristic condition of the anogenital region
      which is histologically similar to bowenoid carcinoma in situ. Some evidence
      suggests a viral origin on the basis of infection with high-risk oncogenic
      genotypes of human papilloma viruses (HPV 16/18 and others) and an association
      with cervical carcinoma. Malignant transformation is rare in bowenoid papulosis.
      The condition usually shows a good response to immuno-modulatory treatment. In
      the following we present our first case of successful treatment with imiquimod, a
      topical immune response modifier which is successfully used in the USA for local
      treatment of condylomata acuminata. Imiquimod creme (Aldara) proved to be a safe,
      efficious and practical patient-applied therapeutic option for the treatment of
      bowenoid papulosis. In view of the oncogenic potential of high-risk HPV
      infections, irrespective of the treatment used, all patients with bowenoid
      papulosis and their sexual partners must be included in long-term follow-up and
      regularly examined for malignant transformation.

PMID- 11244891
TI  - [Shiitake dermatitis: flagellate dermatitis after eating mushrooms].
AB  - The name of flagellate dermatitis originates from self-flagellating medieval
      people. This dermatitis is not rare as a drug eruption following bleomycin
      therapy. An identical skin eruption caused by the mushroom shiitake Lentinus
      edodes is more common but reported mostly from Japan. We saw a 67-year-old
      patient who presented with the typical linear scratch marks after a dinner in a
      Chinese restaurant. The basic mechanism is a toxic epidermal damage. Since it is
      not clear why the dermatitis does not occur frequently since Shiitake is the
      second most popular mushroom in the world, we discuss possible cofactors that may
      trigger the toxic reaction.

PMID- 11244892
TI  - [Contact allergy caused by poison ivy (Toxicodendron spp].
AB  - Within 3 days two female patients presented with an eruption featuring erythema,
      edema, vesicles and bullae. We suspected poison ivy allergy which was
      subsequently proven by history and positive patch tests. In Germany the risk of
      specific hypersensitivity to Toxicodendron species is low, since the distribution
      of such plants is confined to botanical gardens. Other species belonging to the
      family of Anacardiaceae contain urushiols as well (e.g., mango, cashew) and may
      cause allergic contact dermatitis.

PMID- 11244893
TI  - [Occult dermal primary melanoma in congenital nevus-cell nevus].
AB  - Malignant melanomas normally arise at the dermoepidermal junction. Development of
      these tumours in deeper layers of the dermis without having contact with the
      junction is rare. A small congenital melanocytic nevus localized in the region of
      the waist band was excised because of mechanical irritation; it had not shown any
      changes over years. A thorough examination of the whole body did not give any
      clue to a malignant melanoma. Histologically a compound nevus with the typical
      architecture of a congenital melanocytic nevus was found. In the deeper dermis
      there was an isolated nodule of extremely atypical melanocytes with minimal
      pigmentation of melanin. S100 antigen could be demonstrated throughout the whole
      tumour whereas HMB45 was only found at the dermoepidermal junction. There was no
      marking of the tumour cells with a pancytokeratin antibody. A histological
      relationship between the new tumour and a mixed tumour of the left testicle,
      which had been excised 3 years ago, could be excluded. We did not find any
      metastases neither by image-aided methods nor by sentinel lymph node biopsy.

PMID- 11244895
TI  - [Skin care in deep radiotherapy].

PMID- 11244894
TI  - [Sebaceous gland carcinoma of the neck].
AB  - Extraocular sebaceous carcinoma is a rare skin neoplasm that resembles clinically
      pyogenic granuloma, hemangioma or squamous cell cancer. The clinical and
      histological findings are described. The differential diagnosis of common tumors
      of the face should include this rare malignancy.

PMID- 11244896
TI  - [A 9-year-old hyperactive boy with multiple skin-color papules].

PMID- 11244897
TI  - [Cutaneous paraneoplastic syndromes].

PMID- 11244898
TI  - [New developments in medical mycology].
AB  - Not only have the systemic mycoses clearly increased in number but also mycoses
      of the skin are more common than presumed in the past. Today onychomycosis is
      found in up to 10% of human beings. Onychomycosis can compromise quality of life
      markedly. Common tinea pedis is one of the most important risk factors for
      erysipelas of the lower legs. The clinical presentation of oral candidosis in HIV
      infected patients is changing; Candida dubliniensis has been identified as
      another important causative microorganism. Onychomycosis today in most cases can
      be cured using terbinafine or itraconazole. When choosing the ideal drug in a
      given case, both the benefit risk ratio and the benefit cost ratio have to be
      taken into account. Liposomally encapsulated amphotericin B represents a major
      breakthrough in the treatment of systemic mycoses or fever of unknown origin. The
      same applies to liposomally encapsulated econazole with respect to tinea pedis.
      In regard to the pathogenesis of Candida infections the family of secreted
      aspartic proteinases plays a major role as a virulence factor and possible future
      target for antimycotic treatment.

PMID- 11244899
TI  - [Therapy of metastatic malignant uveal melanoma].
AB  - The uvea is the most common site for extra-cutaneous melanoma and uveal melanoma
      is the most frequent primary intraocular tumour in adults. Because its different
      location, biology, histology, genetic features and prognosis in comparison to
      cutaneous melanoma, this tumour is considered as a distinct entity in the group
      of malignant melanoma. While primary uveal melanoma is usually treated by
      ophthalmologic oncologists, metastatic diseases is often managed by dermatologic
      oncologists. Hematogenous spread predominantly involves the liver and is often
      restricted to this organ for a long period. Metastatic uveal melanoma is usually
      resistant to chemotherapeutic regimens established for the therapy of cutaneous
      melanoma. Newer therapeutic modalities, such as local intra-arterial chemotherapy
      into the hepatic artery, perhaps combined with embolisation of feeder blood
      vessels of liver metastases, improves the prognosis of metastatic uveal melanoma.
      Currently the nitrosourea derivate fotemustine is the drug of choice in the local
      hepatic and systemic treatment and seems to be superior to other chemotherapeutic
      agents. Following the characterisation of primary uveal melanoma, we summarize
      the results of different treatment protocols for metastatic disease and give an
      overview of new strategies.

PMID- 11244900
TI  - The psychological effects of Hurricane Andrew on ethnic minority and Caucasian
      children and adolescents: a case study.
AB  - The impact of Hurricane Andrew on 212 African American, Caucasian, and Hispanic
      elementary and middle school children was examined at 6 months postdisaster.
      Using self-report instruments, this case study examined the predictive utility of
      several hypothesized mediators of children's reactions to disaster. Results
      showed higher levels of intrusive symptomatology for girls and for elementary
      school children as compared with their middle school counterparts. No differences
      were found with reference to race. The lack of findings concerning race is
      addressed, as well as implications for future studies.

PMID- 11244901
TI  - In search of cultural diversity: recent literature in cross-cultural and ethnic
      minority psychology.
AB  - The purpose of this study was to identify where the most work on cross-cultural
      and ethnic minority psychology is being published and who the most productive
      authors are. The journals that published the most articles on cross-cultural and
      ethnic minority issues from 1993 to 1999 and the most prolific authors on these
      issues were identified by PsycINFO. Cross-cultural research is cross-national,
      whereas ethnic minority research involves groups of color within the United
      States. The citation impact of these journals and authors was determined from the
      1997 Social Sciences Citation Index. The results suggest that there is very
      limited overlap between the literatures in cross-cultural and ethnic minority
      psychology. Most of the research in these areas is published in specialty
      journals, and there is a paucity of this research in prestigious journals.
      Perceived or actual barriers to publication in prestigious journals may cause
      some to seek specialty journals as outlets for research on cultural diversity.
      The top scholars in cross-cultural psychology are primarily men of European
      ancestry, whereas most of the top scholars in ethnic minority psychology are
      ethnic minority men and women. Strategies to increase the prominence of cultural
      diversity in the psychology literature include combining cross-cultural and
      ethnic minority psychology, increasing the number of editorial board members of
      prestigious journals having expertise in cultural diversity, and increasing the
      quality of specialty journals. Psychology will remain ill-equipped to face the
      challenges of the new millennium without increased attention to cultural
      diversity.

PMID- 11244902
TI  - Adolescent drug use in Mexico and among Mexican American adolescents in the
      United States: environmental influences and individual characteristics.
AB  - The authors compared high school students in Baja California Norte (BCN), Mexico
      (n = 775), with Mexican American students in Los Angeles (LA), California (n =
      516). The students' use of cigarettes, alcohol, marijuana, cocaine, inhalants,
      and other illicit drugs were compared, because these vary by gender, country, and
      their age of first drug use and are influenced by demographic variables,
      individual characteristics, and environmental influences. More BCN students than
      LA students had used alcohol, but more LA than BCN students had used illicit
      drugs and initiated drug use earlier. When demographic variables were
      influential, they were most powerful and increased the risk for drug use more
      than environmental factors or individual characteristics. Environmental factors
      were most influential for boys' drug use, whereas environmental and demographic
      variables were most influential for girls' drug use.

PMID- 11244903
TI  - Ethiopian immigrants' racial identity attitudes and depression symptomatology: an
      exploratory study.
AB  - The relationship between depression and racial identity attitudes of Ethiopian
      immigrants in the United States was investigated. A total of 101 participants
      completed the Tedla-Hopkins Symptoms Checklist-15 (a depression measure) and the
      Racial Identity Attitudes Scale-Amharic and gave demographic information,
      including a brief measure of their reference group. A positive correlation was
      found between preencounter attitudes of racial identity (in which one denies
      oneself membership into one's race) and depression and between preencounter
      attitudes and reference group identification. Depression was best predicted by
      education level. Individuals who endorsed preencounter attitudes of racial
      identity, in which one denies oneself membership into the Black race (pro
      White/anti-Black attitudes), were not only more likely to identify Europeans as
      their reference group but were also significantly more likely to be depressed.

PMID- 11244905
TI  - Counsel of research elders.

PMID- 11244904
TI  - Asian American college students as model minorities: an examination of their
      overall competence.
AB  - Educational success among Asian Americans has led to their being labeled the
      "model minority." At the University of California, Berkeley (UCB), Asian American
      students have higher grade point averages (GPAs) than Hispanic and African
      American but not White students, supporting the notion that Asian Americans are
      more successful compared with other racial minorities. However, success in the
      classroom does not implicate effective functioning in life, and nonacademic
      criteria ought to be considered in assessing the validity of the model minority
      image. Given the increasing diversification of the United States, cross-racial
      engagement may be an additional contributor to overall competence. This was
      empirically tested in a group of 642 undergraduates at UCB, including 291 Asian,
      197 White, 20 African American, 67 Hispanic, and 56 multiracial students. Overall
      competence was operationalized by sense of coherence, that is, the extent to
      which the world is experienced as comprehensible, manageable, and meaningful (A.
      Antonovsky, 1979, 1987). As predicted, Asian Americans had significantly fewer
      numbers of cross-racial groups represented in their friendship network than did
      students of all other races. Lower cross-racial engagement and being Asian (as
      compared with White) were related to a lower sense of coherence, whereas lower
      GPA was not. Within the Asian American subsample, cross-racial engagement was
      again significantly associated with greater coherence, whereas GPA again was not.
      Thus, extending the definition of success to overall competence, these findings
      raise questions about the applicability of the model minority label to Asian
      Americans, despite their academic achievement. Future studies need to assess the
      reasons for their limited cross-racial engagement and lower sense of coherence
      and to examine means to assist the development of these strengths.

PMID- 11244907
TI  - Influences of self-beliefs, social support, and comfort in the university
      environment on the academic nonpersistence decisions of American Indian
      undergraduates.
AB  - This study investigated the influence of self-beliefs, social support, and
      comfort in the university environment on the academic nonpersistence decisions of
      83 American Indian undergraduates. The self-belief construct comprised self
      esteem and 2 dimensions of college-related self-efficacy. The social support
      cluster consisted of 3 variables: family support, friend support, and perception
      of being mentored. The 3rd cluster, comfort in the university environment, was
      measured by perceptions of university environment, cultural congruity, and
      college stress. Although each of the 3 constructs significantly accounted for
      academic nonpersistence decisions, social support was the strongest predictor,
      followed by comfort in the university environment, and then self-beliefs.
      Students who perceived being mentored were more likely to report decreased
      nonpersistence decisions. Similarly, students who had more positive perceptions
      of the university environment were more likely to make fewer nonpersistence
      decisions. Finally, higher self-esteem and greater college-related self-efficacy
      were associated with decreased nonpersistence decisions. Research-informed
      practice implications for increasing the academic persistence of American Indian
      students include fostering mentoring relationships and providing interventions to
      increase social support, self-esteem, and self-efficacy.

PMID- 11244906
TI  - Mental health service use by African American women: exploration of subpopulation
      differences.
AB  - Studies focusing on mental health service use have consistently viewed African
      American women as a homogeneous population, and very few studies have examined
      subgroup differences. However, important differences exist both within and
      between groups in lifestyle, stressors, type and availability of support
      resources, societal interactions, and risk-taking behaviors. This study examined
      rates and patterns of mental health service use by African American lesbian women
      and a matched sample of heterosexual women. Results suggest both similarities and
      differences in factors associated with use of services. Despite evidence of
      substantial emotional distress, relatively few African American lesbian and
      heterosexual women reported current use of mental health services. These findings
      are consistent with past reports on African American heterosexual women but
      differ from other published reports on lesbians' use of therapy. Findings from
      this study, including clear differences between lesbians and heterosexual women
      in past use of therapy and preferences for mental health providers, have
      important implications for service provision.

PMID- 11244908
TI  - 3D CT angiography.

PMID- 11244909
TI  - Quantification using 3D imaging.

PMID- 11244911
TI  - Physiologic changes during laparoscopy.
AB  - The short-term benefits of minimal access techniques include less pain, early
      mobilization, and shorter hospital stay. Nonetheless, significant data have
      accumulated regarding the complications associated with laparoscopic techniques,
      including those that are unique to laparoscopic surgery such as bile duct injury
      and disruption of major blood vessels. Other problems such as myocardial ischemia
      and respiratory acidosis are associated with the cardiopulmonary effects of
      pneumoperitoneum and systemic CO2 absorption. These physiologic changes, although
      tolerated by healthy patients, could have particular adverse consequences for
      infirm and critically ill patients. It would appear that minimizing IAP during
      insufflation decreases the risk of potentially marked cardiovascular changes and
      regional blood flow alterations. In turn, this could arguably decrease the risk
      of perioperative myocardial events, or organ dysfunction or failure. Laparoscopy
      in the critically ill patient is questionable because the role is not
      established. An ICU patient has little to gain from the benefits of early
      mobilization. Conversely, in the presence of raised ICP or borderline organ
      function, the physiologic changes associated with pneumoperitoneum and
      laparoscopy could have profound detrimental effects.

PMID- 11244910
TI  - 3D imaging: musculoskeletal applications.

PMID- 11244912
TI  - Surgical aspects and future developments of laparoscopy.
AB  - Laparoscopy has revolutionized surgery and in the process influenced the practice
      of anesthesiology. This article reviews several minimal access procedures that
      have been accepted into practice, are gaining acceptance, or remain
      investigational. Absolute contraindications to laparoscopy have been emphasized.
      As the threshold for primary care physicians to refer sicker and sicker patients
      for surgery decreases, it is crucial for the anesthesiologist to understand
      physiologic stresses of pneumoperitoneum and the nuances of laparoscopic surgery.
      The anesthesiologist also can be recruited to adjust insufflation pressures,
      tweak images on monitors, rotate and position the patient, or pass balloons and
      bougies. With patient and surgeon expectation of no pain or nausea and early
      discharge, anesthetic choices become vital for the ultimate success of the
      procedure.

PMID- 11244913
TI  - Anesthesia for hysteroscopy.
AB  - Hysteroscopy is becoming a more widely used technique. Diagnostic hysteroscopy is
      replacing conventional dilatation and curettage in the diagnosis of intrauterine
      pathologies. Transcervical endometrial resection is often the first-line surgical
      treatment for dysfunctional uterine bleeding and carries less associated
      morbidity and morality. Overall, the technique is extremely safe, but vigilance
      is required particularly for intravasation of irrigation media. Complications
      such as gas embolus and hypo-osmolar hyponatremia require prompt treatment to
      reduce associated morbidity and morality. Careful monitoring of fluid deficit is
      paramount in avoiding the latter problem. Regional or general anesthetic
      techniques can be used and, in the ambulatory or office-based setting, in which
      these procedures are increasingly performed, the need for "street readiness" can
      influence the choice of the agents used.

PMID- 11244914
TI  - Physiologic changes during thoracoscopy.
AB  - Despite the obvious benefits of minimally invasive surgery, the physiologic
      changes associated with thoracoscopic procedures present multiple challenges. The
      lung is the site of gaseous exchange, but during thoracoscopic surgery it is
      simultaneously either the surgical target organ or responsible for obscuring
      surgical exposure. Thus, there is a conflict of interests between the need to
      provide ideal surgical conditions and the need to maintain normal pulmonary and
      cardiovascular physiology. In an attempt to minimize the physiologic insult
      associated with thoracoscopic surgery, multiple anesthetic and surgical
      techniques have therefore been developed. None are entirely problem free,
      however. Because the physiologic changes are technique specific, a clear
      understanding of the dynamic interaction between the anesthetic-surgical
      technique and patient physiology is essential.

PMID- 11244915
TI  - Anesthesia for thoracoscopy.
AB  - Thoracoscopy has become a widely used method of achieving minimally invasive
      thoracic surgery. The anesthesiologist providing perioperative care for VATS is
      challenged to evaluate the patient carefully; to design a safe anesthetic
      regimen, taking into account preexisting disorders; to ameliorate physiologic
      alterations associated with one-lung ventilation and CO2 insufflation; and to
      provide safe, effective perioperative anesthesia and postoperative pain control.

PMID- 11244916
TI  - Thoracoscopy in the pediatric patient.
AB  - The pediatric applications of minimally invasive surgical procedures such as
      thoracoscopy continue to increase. Specific alterations in anesthetic management
      may be required during the perioperative care of these patients. This article
      reviews the anesthetic care of infants and children during thoracoscopy with
      emphasis on cardiopulmonary disturbances of the patient, techniques to isolate
      the operative and nonoperative lungs and provide one-lung ventilation to improve
      surgical visualization, cardiopulmonary alterations induced by the creation of
      the artificial pneumothorax or the absorption of CO2 by the plural surface,
      intraoperative management of one-lung ventilation, and the potential for and
      treatment of inadvertent CO2 embolism.

PMID- 11244917
TI  - Complications of thoracoscopy.
AB  - Thoracoscopy is a minimally invasive thoracic surgical technique that is gaining
      widespread use for several surgical procedures. Although the complication rate is
      relatively low, there are definable risks associated with the technique. Careful
      attention to patient selection and an understanding of the complications
      associated with one-lung ventilation and video-assisted surgical techniques can
      help one to anticipate and prevent complications.

PMID- 11244918
TI  - Anesthesia for laparoscopy with emphasis on outpatient laparoscopy.
AB  - Laparoscopy has developed extremely rapidly and is currently applicable to
      virtually every surgical subspecialty. Most of the experience is with gynecologic
      laparoscopy, which has been performed for many years. Some of these procedures
      are simple and brief, with minimal gas insufflation. In these cases, respiratory
      compromise is limited, and spontaneous ventilation appears acceptable. Such
      procedures therefore can be performed with the patient under local or regional
      anesthesia, or using the LMA with general anesthesia, because the risk of
      aspiration is small. As laparoscopy has developed, more prolonged operations have
      become possible, but these normally require general anesthesia, controlled
      ventilation, and tracheal intubation. More sophisticated laparoscopic surgery has
      reduced postoperative morbidity, shortened hospital stays, and moved many
      procedures into the outpatient arena. These newer laparoscopic operations present
      many challenges, especially in the provision of adequate analgesia and the
      minimization of PONV. Analgesia should be multimodal, using local anesthesia and
      NSAIDs as first-line therapy. This combination may be sufficient for more minor
      procedures, and the elimination of opioids helps to reduce PONV. For more
      extensive operations, opioids also are required, but should not be the mainstay
      of analgesia. PONV should be treated effectively whenever it occurs, with
      consideration given to the use of prophylactic antiemetics in especially high
      risk groups. Laparoscopic surgery clearly offers significant advantages in many
      cases. Although this technology can make some procedures technically possible on
      an outpatient basis, the morbidity following operations such as laparoscopic
      cholecystectomy is considerable. The ever-greater cost savings from the expansion
      of outpatient surgery is being achieved at the expense of patient discomfort and
      dissatisfaction. Extended care (23 h) could be a better option in some
      circumstances. The future will see further developments in laparoscopic surgery.
      Microlaparoscopy permits simple procedures to be performed with minimal analgesia
      and sedation in an office setting. At present, this technology allows only
      diagnostic and minor operative procedures, the stage at which conventional
      laparoscopy was in the early 1980s. Further developments in optical fibers could
      reduce the requirements for general anesthesia for other operations and
      substantially reduce postoperative morbidity. Until then, laparoscopy continues
      to present many challenges.

PMID- 11244919
TI  - Regional anesthesia for laparoscopy.
AB  - A variety of laparoscopic procedures can be performed on patients under regional
      anesthesia. Diagnostic laparoscopy in elective and emergency patients, pain
      mapping, laparoscopy for infertility, and tubal sterilization are some examples.
      The key benefits of regional anesthesia include less emesis, less postoperative
      pain, shorter postoperative stay, improved patient satisfaction, and overall
      safety. Regional techniques, such as rectus sheath blocks, inguinal blocks, and
      caudal blocks, are useful adjuncts to general anesthesia and facilitate
      postoperative analgesia. Other techniques, such as spinal and epidural
      anesthesia, and combination of the two, are suitable as a sole anesthetic
      technique for laparoscopy. The physiologic changes during laparoscopy in the
      awake patient appear to be tolerated well under regional anesthesia. It is
      reasonable to assume that with advances in instrumentation and surgical
      techniques, the role of laparoscopy will increase in the future. The benefits
      conferred by regional anesthesia make it an attractive option to general
      anesthesia for many patients and procedures. Successful implementation of
      regional anesthesia is an important determinant of how anesthesiologists,
      surgeons, and surgical facilities cope with new challenges. In the future, it
      could be possible to provide "walk-in/walk-out" regional anesthesia with a real
      possibility of fast tracking patients through the recovery process after
      ambulatory surgery. For maximal patient safety, however, facilities offering
      regional anesthesia must have appropriately trained anesthesia personnel and the
      equipment necessary for monitoring and providing full resuscitation in the event
      of complications or a need to convert to general anesthesia.

PMID- 11244921
TI  - Anesthesia for laparoscopy in the pediatric patient.
AB  - Pediatric laparoscopy is a novelty that has yet to be critically assessed in
      large, randomized controlled trials. Just because an operation can be performed
      laparoscopically does not mean it must be done that way. Many procedures can now
      be performed more quickly and cheaply through small incisions without the added
      cardiorespiratory risks seen in laparoscopy. Reports of serious complications are
      beginning to appear in publications. It will become important to compare
      laparoscopic techniques with both open surgery and the minimally invasive
      approach for the same procedure. Many published studies suggest laparoscopy
      offers significant advantages for some operations and for sicker patients.
      Practitioners must have a thorough understanding of the physiologic changes that
      follow pneumoperitoneum and extremes of positioning. As enthusiasm builds, it is
      essential to maintain safety standards. Endoscopists must be appropriately
      trained and peer reviewed. The use of virtual reality models now allows surgeons
      to develop and perfect their laparoscopic skills. When the laparoscopic approach
      is difficult, surgeons must be willing to convert to open surgery rather than
      persevere and risk iatrogenic damage. The role of pediatric laparoscopy has yet
      to be defined, although current trends suggest that it will assume an important
      position in pediatric surgery.

PMID- 11244920
TI  - Laparoscopic surgery during pregnancy.
AB  - Important factors in laparoscopic surgery during pregnancy are listed here: There
      is a risk of aspiration because of a hormonally induced decrease in lower
      esophageal sphincter tone and mechanical effects of a gravid uterus. Supine
      hypotensive syndrome because of aortocaval compression can be a major problem.
      Pneumoperitoneum during pregnancy results in more pronounced restrictive lung
      physiology. Avoid hypoxemia, hypotension, acidosis, hypoventilation, and
      hyperventilation. No anesthetic drugs have been proven to be teratogenic in
      humans. Surgery during pregnancy is associated with the delivery of low birth
      weight, growth-restricted babies. Standard noninvasive monitoring could be
      sufficient for healthy parturients undergoing laparoscopic surgery. Fetal heart
      rate and uterine activity should be monitored pre- and postoperatively.
      Laparoscopic surgery during pregnancy is safe, has multiple advantages over open
      techniques, can be performed during all gestational ages, and does not require
      invasive or continuous fetal and uterine monitoring for routine cases; however,
      the anesthesiologist must be aware of the physiologic changes associated with
      pregnancy and the effects of positioning, and the consequences of CO2
      pneumoperitoneum on the parturient and the fetus. Although no special monitoring
      is required in healthy parturients, each case must be assessed carefully, and
      invasive monitoring could be required in those patients with significant
      cardiovascular or pulmonary disease. Fetal heart rate should be assessed
      preoperatively and postoperatively. Surveillance with an external tocodynamometer
      should be instituted immediately preoperatively and postoperatively and tocolytic
      agents instituted if documented or perceived uterine activity is detected.

PMID- 11244922
TI  - Complications of laparoscopy.
AB  - The frontiers of laparoscopic surgery have extended from gynecologic procedures
      to general surgical techniques. As new applications for laparoscopy emerge,
      anesthesiologists must be familiar with the possible complications associated
      with the various laparoscopic procedures. Only by an appreciation of the
      potential complications of a procedure can their overall incidence be minimized.
      A systematic approach must consider all potential complications during
      laparoscopy. In addition to routine evaluation (i.e., depth of anesthesia and
      volume status), anesthesiologists must confirm that intra-abdominal pressure is
      less than 15 mm Hg, and that inadvertent endobronchial intubation, pneumothorax,
      and gas embolism have not occurred. In the case of precipitous changes in vital
      signs not responding to routine management, it is imperative to release the
      pneumoperitoneum and place the patient in the supine (or Trendelenburg) position.
      After cardiopulmonary stabilization, cautious slow reinsufflation then can be
      attempted. With persistent signs of significant cardiopulmonary impairment,
      however, it is sometimes necessary to convert to an open procedure.

PMID- 11244923
TI  - [Efficiency of diagnosis of latex allergy by the combined use of three latex
      materials for prick-tests].
AB  - The diagnosis of latex allergy is mainly based on prick-tests. In order to
      improve the efficiency of the diagnosis, a comparative study of three latex
      materials is carried out in 64 controls and 29 patients allergic to latex =
      Stallergenes and Allerbio extracts, prepared from crude natural latex, and an
      ammoniated emulsion of rubber latex (AEL). No adverse reactions are recorded. The
      specificity is 100% for both extracts, 85% for AEL. Sensitivity is respectively
      68%, 63%, 72%. The range of values of the wheal is significantly narrower for
      Stallergenes extract. 46% of allergic patients are reactive to the three
      materials. The combined use of three materials reaches an 80% efficiency similar
      to that of Rast Cap System and the addition of three prick-tests and Rast obtains
      an efficiency of 93.1%. Using several latex materials could increase the
      efficiency of the diagnosis, inasmuch as the extracts are generated from natural
      latex, whereas patients are sensitized to manufactured products originating from
      ammoniated latex.

PMID- 11244924
TI  - [Management of atopic dermatitis: practical guidelines suggested by the
      conclusion of systematic assessment in 500 children].
AB  - Allergic management of AD may be worthwhile since allergy may trigger the
      disease. A systematic evaluation of sensitizations overtime and study of their
      clinical involvement in 500 children with AD was carried out, including minor,
      moderate, and severe patients (defined by clinical scores). Standardized methods
      assessed the possibility of contact dermatitis as well as IgE dependant
      allergies. Contact dermatitis concerned fragrances and nickel. Contact dermatitis
      was observed in minor and moderate AD with a progressive increase: 11% of
      children under 2 years and 58% in those over 15 years of age. Later in older
      children, sensitization to cosmetics and occupational allergens occurred in close
      connection with the specific environment. As for IgE sensitization, investigation
      should be electived advised in moderate and severe AD. Inhalant allergen
      sensitization was observed in 66% in moderate AD and 93% in severe AD in the
      group of 7 or 15 years. Clinical confrontation was a better indicator of
      cutaneous involvement than atopen patch-test. It mainly concerned respiratory
      symptoms. In severe AD, food allergy was constantly observed and presented as a
      marker for severe atopic dermatitis. The main trophallergen differ according to
      the age and cultural habits: in children under 2 years of age, eggs, peanuts,
      milk, fish were the main offending agents. Later, main trophallergens were wheat
      flour, shellfish. Although spontaneous decrease of food allergy is sometimes
      observed, it must be pointed out that food allergy may still persist as a
      triggering factor in teenagers as well as in adult-hood. The allergologic
      diagnosis of atopic dermatitis should not focus on IgE dependent sensitization
      without patch testing.

PMID- 11244925
TI  - [Percutaneous sensitization to almond oil in infancy and study of ointments in 27
      children with food allergy].
AB  - A five month old child with atopic dermatitis developed contact dermatitis to
      almond with positive patch test, positive prick test, and class 4 anti-almond
      IgE. Focal lesions of persistent eczema were correlated with application of
      almond oil for 2 month on cheeks and buttocks. The child had not ingested almond
      and her mother did not report almond intake during her breast-feeding. This
      observation points to the problems of possible percutaneous sensitisation to food
      proteins. The study of skin ointments containing components of food origin in 27
      food sensitized atopic patients confirm that the choice of an ointment for
      lesional skin is of importance.

PMID- 11244926
TI  - [The role of the pharmacist in the educational charge of the asthmatic patient].
AB  - The problem of educative charge of the asthmatic patient has mobilised general
      physicians, specialists and kinesitherapists for many years. The first mutual aid
      associations for asthmatic patients, created at the initiative of pneumologists
      and allergists or their patients date back for a score or so of years and their
      principal objectives are the adaption of educational measures, in transmission of
      clear information and in the loan of surveillance equipment, to ensure that
      inhalation equipment is adapted appropriately to the case. Since, the
      mediatisation has reinforced this action in all directions, in the interests of
      and for the great benefit of asthmatic patients; and so the role of the
      pharmacist has also become essential not only in the field of information but
      also in that of control of the self-evaluation of the patient; three inseparable
      aspects are thus emphasized: information aspect, technical aspect, initiation of
      surveillance of the illness.

PMID- 11244927
TI  - [The mesorectum: improvement and anatomy of a semantic error].
AB  - AIMS: The cancer of the rectum touches 10,000 patients per year in France. Its
      treatment is mainly surgical. 50% of the treated patients will die of their
      cancer, either by loco-regional recurrence, or by metastatic disease. The rates
      of local recurrence vary from 10 to 40%. Heald is first who brought back
      recurrence rates lower than 4%, results obtained by the only surgical treatment.
      This treatment included the total exeresis of cellulo-fatty tissue surrounding
      the rectum, tissue which was baptized mesorectum. The aims of this work is to
      define and describe this space, and to discuss its Christian name. MATERIAL AND
      METHODS: The anatomical study carries on the dissection of 2 frozen pelvis of
      fresh man, one cut transversely on the level of L4, the other half-compartment
      sagittaly, then defrosted for the dissection. RESULTS: The mesorectum is defined
      and its various structures, fascia, vessels and nerves, are detailed. CONCLUSION:
      The mesorectum is an anatomical and surgical structure individualisable. Its
      recognition and its importance were born from the understanding of the fascia and
      the rectal anatomy. Its exeresis decreases the rate of the local recurrence (18).
      The technique of exeresis of the mesorectum must be validated, standardized, in
      order to be reproducible in the treatment of the cancer of the rectum.

PMID- 11244928
TI  - The arrangement of the trabecular bone in the vestibular surface of the human
      fetus mandible. A scanning electron microscopy study.
AB  - The characteristics of trabecular bone in human fetuses at seven to nine months
      of intra-uterine life were studied in the vestibular surface of the mental and
      body portions of the mandible. In the mental portion, many circular trabeculae
      joined by "bridges" were observed in the alveolar region (AR). In the 8-month old
      fetus are trabeculae with tortuous disposition in the medium region (MR). Oblique
      trabeculae with superior and inferior dispositions defining a triangular area
      (future mental fossae) are verified in 9-month old fetuses. Trabeculae circularly
      disposed and vascular foramina are present close to the apex of this area. In the
      basilar region (BR) some trabeculae obliquely oriented are observed disposed near
      to the mandibular symphysis. The longitudinal bundles of collagen fibers assume
      an antero-posterior direction. At 9-month age the vascular foramina range from 6
      to 20 microns and the osteocyte lacunae ranging from 1 to 4 microns diameter, are
      present in mandibles from all ages examined. In the body portion the presence of
      circular trabeculae joined by "bridges" is the main characteristic of the AR. In
      the MR most of the trabeculae are circular and the longitudinal trabeculae of
      this region assume an antero-posterior direction. The laminar, antero-posterior
      and juxtaposed trabeculae lying parallel to mandible base are a characteristic of
      the BR. The bundles of collagen fibers exhibit the same pattern of the
      trabeculae. The vascular foramina of the BR are smaller than that of the
      precedent regions. In the body portion of the mandible from all ages examined the
      osteocyte lacunae range from 1 to 4 microns in diameter.

PMID- 11244929
TI  - A connecting branch between the musculocutaneous nerve and the median nerve.
AB  - We report here a connecting branch between the musculocutaneous and the median
      nerves in a 42 years old male cadaver. The connecting branch was 8 cm in length
      and 3 mm in width. One of the brachial veins and the brachial artery were located
      between the roots of the median nerve and the second brachial vein was present
      between the connecting branch and the median nerve. These kinds of variations may
      effect the venous return and may cause edema in the upper extremities.
      Additionally, variations of these nerves have an importance during operations of
      this region.

PMID- 11244930
TI  - [Emergence and course of the ilioinguinal nerve of the groin].
AB  - The aim of our study was to find a way of preserving the ilioinguinal nerve
      during surgical procedures for the repair of inguinal hernias. 40 inguinal
      regions were dissected, 37 ilio-inguinal nerves studied. The emergence of the
      nerve was at 4.21 cm of the anterior superior iliac spine, at 0.78 cm of the
      inguinal ligament on average. Its course was parallel to the inguinal ligament,
      always lay under the aponevrosis of the external oblique abdominal muscle, it
      passed through the superficial abdominal ring in 67.56% before proceeding on
      anterior side of spermatic cord. This result allowed us to examine the
      possibility of the nerve course variation's, of anastomosis with iliohypogastric
      nerve and particularly the best way to identify it when surgical procedures are
      performed in the lower portion of the abdomen.

PMID- 11244931
TI  - Preduodenal portal vein in the adult.
AB  - We present three cases of preduodenal portal vein in adult people, which were
      diagnosed in our department. All of them were identified during elective
      operation for cholelithiasis, caused some technical difficulties to the
      performance of the operation, but led to no major intraoperative or postoperative
      complications. None of them had any preoperative symptoms, which could be related
      to this anomaly. The preduodenal portal vein is a rare congenital anomaly, which
      is usually discovered in infants or children due to the obstruction of the
      duodenum. In adults, it is often asymptomatic, and is usually discovered as an
      accidental finding during laparotomy for other reason. The postcontrast CT can
      set the diagnosis, when this anomaly is suspected. Despite its rarity, this
      anomaly is of great surgical importance, because it can predispose to
      intraoperative complications including hemorrhage from the abnormal vein, or
      damage to the biliary tract or the distented duodenum. The anterior position of
      the portal vein results from the persistence of the ventral anastomosis between
      the two vitelline veins and the distal portion of the right vitelline vein, with
      subsequent atrophy of the cranial part of the left vitelline and dorsal
      anastomotic vein.

PMID- 11244932
TI  - [Apropos of the "Lesson in anatomy"].
AB  - Some striking features from the famous lesson of Prof. Tulp are presented: the
      implication of the spectator in the scene, the unity of the action exalted by the
      "chiaroscuro", the expression of the movement and of Tulp's personality. In
      addition, the probable scientific and philosophical underlying thoughts of
      Rembrandt are discussed having respect to historical data concerning Descartes
      and Constantin Huygens. The indications given by the lesson of Pr. Deyman about
      Rembrandt's conception of this subject and the evolution of his art, are then
      presented. Among the "Anatomy lessons" of the Dutch painting which have preceded
      and followed those by Rembrandt, the three having particular relevance to the
      Master are discussed, allowing to better appreciate his originality, his
      audaciousness and his mastery of his art.

PMID- 11244934
TI  - [Morphological studies of myocardial fibrosis in different types of Keshan
      disease].
AB  - OBJECTIVE: To clarify the localization, distribution, content and type of
      collagen in the myocardium of patients with Keshan disease (KD). METHODS:
      Picrosirium red staining, polarization microscopy and image analysis were used to
      study autopsy specimens from 335 KD patients. RESULTS: A loose network of
      collagen and a higher ratio of type III collagen were found in the myocardial
      scar tissues of acute KD patients. In the myocardial scar tissues from chronic KD
      patients, the collagen fibers were dense, the ratio of type I collagen was
      higher, the ratio of type I to type III is increased in chronic KD and decreased
      in acute KD. The amount of collagen in non-necrotic regions was significantly
      higher than that of the controls. CONCLUSION: The degeneration and necrosis of
      myocytes in KD is associated with disorders of collagen metabolism and with
      structural modelling of collagen.

PMID- 11244933
TI  - [Morphological observations of tumors in the cardiac conduction system].
AB  - OBJECTIVE: To investigate the incidence of tumors in the cardiac conduction
      system (CCS) and to study their relation to sudden deaths. METHODS: The CCS from
      149 cases of sudden death without extracardiac cause of deaths and those from 737
      cases of non-cardiac death were sampled using technique designed by the authors.
      Routine histological examinations were carried out. RESULTS: Tumors in the CCS
      were found in 12 cases (1.35%). Another case with tumor in the CCS was found in a
      specimen received for consultation. Of these 13 tumors, 10 were primary benign
      tumors affecting the CCS, 3 were metastatic tumors. The benign tumors included
      fibroma, hemangioma, lipomatous hypertrophy of the atrial septum, mesothelioma
      and rhabdomyoma. 8 of the 10 cases were located in the SAN or AVN. All the
      metastatic tumors were in the SAN. Of the 13 cases, 3 died suddenly. CONCLUSION:
      Tumors in the CCS are the smallest tumors which can cause sudden death.

PMID- 11244935
TI  - [The clinicopathological study on 41 cases of cardiac tumors].
AB  - OBJECTIVE: To analyze the relation between the pathological changes and the
      prognosis of cardiac tumors through the clinicopathological study on 41 cases of
      cardiac tumors. METHODS: The study was carried out by using the common and
      special histochemical stainings. RESULTS: 39(95.1%) tumors were benign, including
      myxoma, fibroma, and rhabdomyoma; while 2(4.9%) tumors were malignant, including
      neurofibrosarcoma and malignant mesothelioma. In the myxomas group, 75% patients
      were female, 91.7% tumors existed in the left atrium. CONCLUSIONS: The results of
      the clinicopathological study showed that the cardiac tumors were quite different
      from the tumors in the other sites, i.e. even benign ones could cause fatal
      hemodynamic disturbance, hence early diagnosis and early operation are necessary.
      The prognosis of the malignant tumors is worst.

PMID- 11244936
TI  - [A study on abnormal chondrocyte differentiation and abnormal expression of
      collagen types in articular cartilage from patients with Kaschin-Beck disease].
AB  - OBJECTIVE: To study the abnormal characteristics of chondrocyte differentiation
      and abnormal expression of collagen types in articular cartilage from patients
      with Kaschin kaschin-Beck disease (KBD). METHODS: The abnormal differentiation
      and expression of collagen types I, II, III, IV and X in articular cartilage from
      five cases of KBD patients were examined using monoclonal immunohistochemical
      methods. RESULTS: (1) The expression of tyep II collagen was decreased in the
      upper zone in KBD articular cartilage. (2) The expression of types I, III and VI
      collagen were found throughout the articular cartilage, but type X collagen was
      located in the calcified cartilage zone and around chondrocyte clusters in the
      deep zone. (3) Chondrocyte clusters exhibited significant pericellular staining
      for types I, II, III and VI collagen, but did not stain with any collagen
      antibody in the chondronecrosis areas. CONCLUSION: The abnormal collagen pattern
      in the articular cartilage of KBD patients was similar to that seen in primary
      osteoarthritic cartilage, but having more pronounced type I collagen expression
      in the surface zone and no collagen expression in the chondronecrosis areas.

PMID- 11244937
TI  - [The sensitivity of carcinogenic initiation effect of regenerated liver induced
      by diethylnitrosamine in rats].
AB  - OBJECTIVE: To compare the sensitivity of carcinogenic initiation effect of
      regenerated liver with normal liver induced by diethylnitrosamine (DEN) in rats.
      METHODS: Experimental group was composed of rats that had 2/3 of their liver
      excised 8 weeks previously, normal rats were used as controls to study: (1)
      weight of their livers, conventional histological examination and 3H-TdR
      incorporation test; (2) a modified Solt-Farber carcinogenesis scheme was applied
      in order to detect the degree of carcinogenic initiation effect by stereologic
      study of GGT positive preneoplastic liver cell foci; (3) damage of DNA in
      hepatocytes were detected by in situ nick translation test after DEN treatment
      both in vivo and in primary cultured liver cells. RESULTS: (1) the regenerative
      process in liver was completed by the end of the 8th post-operative week and no
      proliferation of hepatocytes was detected. (2) both the number and volume density
      of GGT positive foci in the experimental group were higher than those in control
      group. (3) DNA damage in hepatocytes of experimental group were more severe than
      in the control group. CONCLUSION: Even after the regeneration process was
      completed, the regenerated liver still possessed higher sensitivity to
      carcinogenic initiation effect than normal liver, this sensitivity was related
      with the severity of DNA damage in hepatocytes of the regenerated liver after DEN
      attack.

PMID- 11244938
TI  - [Expression of class II major histocompatibility antigen and factor VIII related
      antigen in endothelial cells of blood vessels in malignant lymphomas].
AB  - OBJECTIVE: To determine the heterogenicity in the expression of class II major
      histocompatible antigen (HLA-DR), factor VIII related antigen (FVIIIRAg) and the
      biological behavior of vessel endothelial cells in malignant lymphoma. METHODS:
      Standard immunohistochemical method using antiserum of HLA-DR and FVIIIRAg were
      applied to detect heterogeneous expression of endothelial cells in 39 cases of
      malignant lymphomas using neonatal lymph nodes, normal adult lymph nodes and
      lymph node hyperplasia as the controls. RESULTS: Both HLA-DR and FVIIIRAg
      reactivity was found in blood vessels in neonate lymph nodes, normal adult lymph
      nodes and lymph node hyperplasia. Most vessels in Hodgkin's disease and T cell
      lymphoma had high endothelial post capillary venules (HEV), which expressed both
      FVIIIRAg and HLA-DR. In B cell lymphoma, most blood vessels are capillary-like
      microvessels, which expressed little or no HLA-DR, only expressing FVIIIRAg.
      CONCLUSIONS: The above results indicate that the endothelial cell of blood
      vessels in Hodgkin's disease and T cell lymphoma not only participate in
      immunoregulation but also in blood coagulation, whereas, those in B cell lymphoma
      only participate in blood coagulation.

PMID- 11244939
TI  - [The relationship between laminin and laminin receptor expression to metastasis
      and survival of breast carcinomas].
AB  - OBJECTIVE: To investigate the relationship between laminin (LN) and LN receptor
      (LN-R) expression to breast carcinoma metastasis and survival. METHOD: The LSAB
      immunohistochemical method was used to study cytoplasm of primary breast cancer
      tissue from 109 cases and 37 axillary lymph nodes with metastasis. RESULTS:
      Immunostaining of LN was detected in 32 (29.4%) primary breast carcinoma and in 5
      (13.7%) axillary nodes with metastasis. The expression of LN-R was significantly
      lower in primary breast carcinomas (55.0%) than in the node-positive tissues
      (83.8%) (P < 0.05). Among the 64 cases followed up none of the 6 patients with LN
      positive alone died after 3 years. Whereas, the LN-R positive (including LN-R
      positive alone or both LN and LN-R positive) cases had a significantly poorer
      prognosis when compared with the LN-R negative cases (P < 0.001). Multivariate
      analysis of clinical and pathological data by Cox regression method demonstrated
      that both LN-R expression and lymph node status were independent factors
      affecting the survival of breast cancer patients, but the former had a higher
      risk (odds ratio = 4.375) than the latter (OR = 2.810). CONCLUSION: These results
      suggest that LN-R expression is an important biofactor for predicting the
      prognosis of breast cancer.

PMID- 11244940
TI  - [The role of the heat shock protein in human breast cancer].
AB  - OBJECTIVE: To study the role of heat shock proteins (HSP) in the cell cycle and
      various processes of carcinogenesis. METHODS: Immunohistochemical SP methods,
      electron microscopy, in situ hybridization and RT-PCR were used to evaluate the
      expression of HSP, mainly HSP90, ubiquitin and HSP70 in breast cancer tissues.
      RESULTS: HSP90 mRNA was expressed at much higher levels in cancerous tissue than
      in non-cancerous tissues. In addition, a close relation between HSP90 mRNA
      expression and proliferating cell nuclear antigen labelling index (PCNA L. I.)
      was observed in cancerous tissue. These findings suggest that increased
      expression of HPS90 isoform may play a role in cell proliferation. On the other
      hand, HSP90 mRNA was expressed in the more poorly differentiated carcinomas of
      the breast. The intracellular localization of HSP70 was consistent with that of
      ubiquitin. The PCNA L. I. was significantly higher in specimens showing HSP70 in
      nucleus. HSP73 mRNA, a member of HSP70 family, was also expressed at higher
      levels in cancerous tissues associated with a high PCNA L. I. than in non
      cancerous tissues. CONCLUSION: These results suggest that HSP90 may play a role
      in cancer cell proliferation and that HSP90 may contribute to cell
      differentiation and structural constitution. In addition, HSP70, especially
      HSP73, is related to ubiquetin and seems to be a marker for cancer proliferation.

PMID- 11244941
TI  - [A clinicopathological study on panniculitic T-cell lymphoma].
AB  - OBJECTIVE: To analyse the pathomorphology and clinical behavior of panniculitic T
      cell lymphoma (PTCL) and to study the classification and name of PTCL. METHODS:
      Routine pathological and immunohistochemical methods were utilized to analyse 4
      cases of PTCL. RESULTS: All patients presented with 1 to 3 cm diameter
      subcutaneous nodules accompanied by high fever. The clinical course of these
      patients was distinctive and progressive. All patients died within 4-9 months.
      Histologically, the lesions were composed of medium sized atypical cells
      (CD45RO+) infiltrating between fat cells, large numbers of bean bag cells (CD68+)
      could be observed. CONCLUSIONS: PTCL is a type of peripheral T-cell lymphoma
      which is highly malignant.

PMID- 11244943
TI  - [A study on the anti-metastatic effects of CD3Ak cells in nude mice].
AB  - OBJECTIVE: To investigate whether cancer draining lymph node lymphocytes
      activated by CD3 McAB in vitro have anti-tumor effects in vivo. METHODS: Nude
      mice with highly metastatic human ovarian cancer were treated with CD3 McAB
      activated killer cells (CD3AK) from human ovarian cancer draining lymph node
      lymphocytes. 31 experimental nude mice were divided into 4 groups; the cisplatin
      group (7 mice), the CD3AK cells group (7 mice), the combined treatment group (7
      mice), and control group (10 mice). Treatment began on the 10th day after tumor
      transplantation for a total of 80 days. RESULTS: The transplanted tumors
      disappeared in 1 mouse of CD3AK group, significant difference in the anti
      metastatic effect was found between the CD3AK group (2/7 mice with metastasis)
      and the control group (8/10 mice with metastasis). Significant difference in
      average tumor volume was found between the CD3AK group (0.5788 +/- 0.2549) and
      the control group (1.5685 +/- 0.283). The tumor growth inhibition rate reached
      63.1% in the CD3AK group. Significant difference in the serum level of
      progesterone was found between the CD3AK group (3.3843 +/- 0.5314) and the
      control group (6.3480 +/- 0.7615). Significant difference in the histiocyte
      increase in the lymph node sinuses was found between the CD3AK group (59/69) and
      the control group (55/94). CONCLUSION: These results suggest that CD3AK cells
      appear to be effective in tumor growth inhibition, anti-metastasis and enhancing
      host immunologic function.

PMID- 11244942
TI  - [Multivariate analysis of clinicopathological and immunohistochemical factors in
      colorectal carcinomas].
AB  - OBJECTIVE: To determine the effect of clinicopathological and immunohistochemical
      factor on the prognosis of colorectal carcinoma. METHODS: The Cox model was used
      in a series of 68 colorectal carcinomas to study ten prognostic factors. These
      factors included tumor growth, stromal lymphocyte infiltration and fibrous tissue
      proliferation, degree of differentiation, Dukes stage, p53 protein, c-erbB-2
      protein, P21 protein, PCNA proliferation index and EGFR. RESULTS: Monovariate
      analysis showed that tumor growth, stromal lymphocyte response, Dukes stage, p53,
      c-erbB-2 protein and PCNA index influenced prognosis significantly; multivariate
      analysis revealed 4 significant prognostic factors; P21, c-erbB-2 protein, Dukes
      stage and PCNA index. The relative risk (RR) for mortality was high in patients
      having P21 and c-erbB-2 co-expression. The RR of P21 and c-erbB-2 protein
      positive patients in Dukes A stage was higher than that of P21 and c-erbB-2
      protein negative patients in Dukes B stage. CONCLUSIONS: P21, c-erbB-2 protein,
      PCNA index and Dukes stage were independent predictors of survival. The prognosis
      of patients with P21 and c-erbB-2 protein co-expression was worse than in
      patients without this co-expression.

PMID- 11244944
TI  - [Can telepathology work for us].

PMID- 11244945
TI  - [Modified lipoproteins in atherosclerotic lesions of human aorta].
AB  - OBJECTIVE: To study the distribution patterns, amount, as well as the physical
      and chemical properties of malondialdehyde (MDA) and 4-hydroxynonenal (HNE)
      modified apolipoprotein B (apo B) in atherosclerotic lesions of human aorta. The
      distribution patterns of MDA and HNE modified apo B were also compared with those
      of lipoprotein(a) [LP(a)] and apo B. METHODS: Immunohistochemistry, electronic
      microscopy, immunoelectronic microscopic and biochemistry methods were used for
      qualitative and quantitative analysis. RESULTS: It was found that the
      distribution of MDA and HNE modified apo B coincided with Lp(a) and apo B in the
      extracellular matrix. While the distribution of MDA-apo B and HNE-apo B in foam
      cells appeared annular or particulate, similar to ceroids but different from that
      of Lp(a) or apo B. The physical and chemical properties of LDL from lesions on
      the intima were similar to those of in vitro modified LDL. In addition, a higher
      level of aldehyde modified LDL was extracted from the lesion areas than from
      normal intima. CONCLUSION: Oxidative modification of apo B containing
      lipoproteins is necessary for atherogenesis.

PMID- 11244946
TI  - [Molecular pathology of mitochondria in aging].

PMID- 11244947
TI  - [A study of prognostic factors in breast cancer: histological grading].
AB  - OBJECTIVE: To study the significance of histological grading as a prognostic
      factor in breast cancer. METHODS: According to the grading systems of Bloom
      Richardson and Elston, 476 cases of invasive ductal carcinoma (IDC) with more
      than 5 year follow-up were assessed for grade I (GI, 72 cases), grade II (G II,
      216 cases) and grade III (G III, 188 cases). RESULTS: The 5 year survival rate
      for IDC G I, G II and G III were 81.9% (59 cases), 63.4% (137 cases) and 49.5%
      (93 cases) respectively. CONCLUSION: Histological grading of IDC is as good a
      prognostic factor as their clinical stage.

PMID- 11244948
TI  - [A pathological study on obliterative arteriopathy in human renal allografts].
AB  - OBJECTIVE: To observe the histopathological changes of obliterative arteriopathy
      (OBA) in human renal allografts, analyse OBA cellular components and probe its
      pathogenesis. METHODS: 74 renal allografts removed due to acute vascular
      rejection and chronic rejection were studied by light microscopy, electron
      microscopy and immunohistochemistry methods. RESULTS: OBA predominately affected
      the intima of interlobar, arcuate and interlobular arteries in all the 74 renal
      allografts. 29 cases developed OBA within 3 months post transplantation. 19
      (25.7%) renal allografts showed early OBA with intimal arteritis, 55 (74.3%)
      cases had advanced OBA with intimal spindle-shaped smooth muscle cell (SMC)
      proliferation and intimal fibrosis. The cellular composition of OBA consisted of
      two origins, one from the host and the other from arterial wall intrinsic cells
      of renal allografts, including T lymphocytes; monocyte/macrophage cells;
      endothelial cells and different phenotypes--"contractile" or "synthetic" SMCs,
      "synthetic" SMCs secreted collagen types I, III. CONCLUSION: Our findings suggest
      that OBA is a post transplantation intrarenal arterial wall proliferative lesion.
      It is the result of a series of interactions between host immunocytes and
      allograft vascular wall cells. OBA is a type of immune reaction.

PMID- 11244949
TI  - [The killing effects of two prodrug sensitivity genes on human pancreatic
      carcinoma cells PC-2].
AB  - OBJECTIVE: To compare the killing effects of herpes simplex virus thymidine
      kinase (HSV-TK)/ganciclovir (GCV) system versus cytosine deaminase (CD)/5
      fluorocytosine (5-FC) system on human pancreatic carcinoma PC-2 cells. METHODS:
      Recombinant retroviral vectors expressing HSV-TK and CD genes were constructed
      and transduced into pancreatic carcinoma cell line. Prodrug sensitivity and IC50
      values (concentration of drug at which cell growth is inhibited by 50%) of the
      transduced cells were measured by MTT method. The bystander effects in the two
      systems were also compared. RESULTS: The IC50 value of HSV-TK-transduced cells to
      GCV was (1.06 +/- 0.12) micromol/L and 558-fold lower than parental PC-2 cells,
      while the IC50 value of CD-transduced cells to 5-FC.00 was (33.00 + 0.95)
      micromol/L and 258-fold lower than parental PC-2 cells. Mixed cells containing
      10% of transduced cells showed 39% and 50.3% growth inhibition in TK/GCV and CD/5
      FC systems respectively. CONCLUSION: Both HSV-TK/GCV and CD/5-FC systems showed
      effective antitumor activity in vitro to pancreatic carcinoma PC-2 cells. The
      therapeutic index of HSV-TK/GCV system is higher, but its bystander effect is
      lower than that of CD/5-FC system.

PMID- 11244950
TI  - [Ultrastructural morphometric studies of fat storing cells in human chronic viral
      hepatitis].
AB  - OBJECTIVE: To study the dynamic changes of fat storing cells (FSC) in human
      chronic viral hepatitis. METHODS: Liver biopsies from 5 chronic persistent
      hepatitis (CPH), 5 mild chronic active hepatitis (CAH), 6 moderate CAH, 5 severe
      CAH cases and 8 normal liver tissues were used to investigate the number,
      appearance and organellae of FSC in non-fibrotic areas by cell counting under
      light microscope with semi-thick sections and morphometric study under electron
      microscope. RESULTS: The number of FSC in non-fibrotic areas of CAH groups were
      decreased significantly compared with the normal group and CPH group; the
      percentages of transitional cells tended to increase along with the increase in
      degree of severity of liver fibrosis, some of the FSC were transformed into
      fibroblasts. CONCLUSIONS: During the progress of liver fibrosis caused by CAH,
      FSC were constantly transformed into fibroblasts which tended to migrate to the
      fibrous septum of the hepatic lobules.

PMID- 11244951
TI  - [The suppressing effect of TIMP-3 gene transfection on the invasion and
      metastasis of human lung carcinoma cells line].
AB  - OBJECTIVE: The purpose of this study is to determine if increasing levels of
      tissue inhibitor of metalloproteinase 3 (TIMP-3) expression could suppress the
      malignant phenotype of human cancer cells. METHODS: The recombinant expression
      vector, which contains full length cDNA of human TIMP-3, was constructed and
      transfected into BE1 cell line by lipofectin technique. The invasive and
      spontaneous metastatic potential was examined. RESULTS: TIMP-3 mRNA expression in
      TIMP-3 gene transfected BE1 cells was upregulated as detected by Northern blot.
      The invasion of TIMP-3 gene-transfected cells across matrigel-coated filters was
      significantly decreased when compared with controls. Following subcutaneous
      injection into nude mice, the TIMP-3 transfected cells suppressed primary tumor
      growth, as characterized by reduced tumor incidence (9/12 vs 6/6), longer latency
      and reduced metastatic potential to the lungs (1/12 vs 5/6) and lymph nodes (5/12
      vs 6/6). CONCLUSION: The results suggest that upregulation of TIMP-3 expression
      in BE1 cells resulted in suppression of the invasive potential of BE1 cells in
      vitro as well as tumorigenic and metastatic potential in nude mice.

PMID- 11244952
TI  - [Platelet-derived growth factor (PDGF) mRNA expression of porcine pulmonary
      artery smooth muscle cells induced by hypoxic endothelial cells conditioned
      medium].
AB  - OBJECTIVE: To study the effect of hypoxic endothelial cell conditioned medium on
      the autocrine of PDGF in porcine pulmonary artery smooth muscle cells (PASMC).
      METHODS: Experimental groups included serum-free medium group (control group),
      normoxic endothelial cell conditioned medium (NECCM) group and hypoxic
      endothelial cell conditioned medium (HECCM) group. The expression of PDGF-A and 
      B chain mRNA was determined by in situ hybridization and image analysis. RESULTS:
      A weak expression for PDGF-A and PDGF-B mRNA was observed in PASMC cultured in
      serum free medium (control group); HECCM markedly enhanced the expression of PDGF
      A and PDGF-B mRNA in PASMC, both being about 1.8-fold and 1.73-fold of the
      control group respectively, and 1.4-fold and 1.5-fold of the NECCM group
      respectively (P < 0.01). CONCLUSION: PDGF may be an autocrine growth factor of
      PASMC induced by HECCM and may play an important role in vascular structural
      remodeling of hypoxic pulmonary hypertension.

PMID- 11244953
TI  - [Expression of telomere and telomerase in human primary gastric carcinoma].
AB  - OBJECTIVE: To investigate the expression of telomere restriction fragments (TRF)
      and telomerase activity in human primary gastric carcinoma tissues and their role
      in tumor transformation and progression. METHODS: The lengths of TRF and activity
      of telomerase were observed in 17 early gastric carcinoma tissues and 89 advanced
      gastric carcinoma tissues, using hybridization of nucleic acids directly in
      agarose gels and telomere repeat amplification protocol (TRAP) assays,
      corresponding normal gastric mucosa were used as controls. RESULTS: The TRF
      lengths and telomerase activity in gastric cancer tissues were significantly
      shorter or higher than those in non-tumor mucosa, and the expression of
      telomerase activity in abnormal TRF tumor tissues was significantly higher than
      that in normal TRF tumour tissues. Alterations of TRF and telomerase activity in
      advanced tumour tissues were higher than those in early tumor tissues. Moreover,
      significant differences in TRF length were observed between well differentiated
      and poorly differentiated adenocarcinomas. CONCLUSION: Abnormal TRF status and
      telomerase reactivation may correlate well with malignant progression of gastric
      cancer. Telomerase activity and TRF lengths may thus serve as an important
      additional marker for tumor diagnosis.

PMID- 11244954
TI  - [The expression of plasminogen activator inhibitor-1 (PAI-1) gene in human
      astrocytomas].
AB  - OBJECTIVE: To investigate the expression of PAI-1 gene and its clinical
      significance in human astrocytomas. METHODS: The mRNA and protein expression of
      PAI-1 were examined with Northern blot hybridization and ABC immunohistochemical
      methods in 36 cases of astrocytomas. The correlation between PAI-1 expression
      with clinicopathologic factors were studied. RESULTS: All astrocytoma tissues
      expressed 3.0 kb and 2.2 kb transcripts of PAI-1 mRNA. The PAI-1 mRNA level in
      high grade astrocytomas were considerably higher than that in low grade
      astrocytomas (P < 0.01). Detectable levels of PAI-1 mRNA were not found in normal
      brain tissues. PAI-1 mRNA expression was positively correlated with necrosis (r =
      0.51, P < 0.01), micro-blood vessel quantity (r = 0.33, P < 0.01) and brain edema
      (r = 0.27, P < 0.01) respectively. There was no correlation between PAI-1 mRNA
      expression and tumor size, sex or age of patients. Immunohistochemical staining
      for PAI-1 showed the distribution of PAI-1 protein was mainly in tumor cells of
      high grade astrocytomas, particularly in abundant areas of vascular proliferation
      and in remnant tumor cells surrounding necrotic foci, whereas it was only weakly
      expressed in low grade astrocytomas. CONCLUSION: The expression of PAI-1 gene was
      closely associated with grade, necrosis, angiogenesis and brain edema, which may
      provide a molecular marker for determining the malignant degree of astrocytoma.

PMID- 11244955
TI  - [Correlation of expression of connexin 43 and cardiomyocyte hypertrophy].
AB  - OBJECTIVE: To study the relationship between the expression of connexin 43 and
      cardiomyocytes hypertrophy. METHODS: Cardiomyocytes were isolated from newborn
      Wistar rats. Norepinephrine (NE) or phenylephrine (PE) were added into the media
      to induce myocyte hypertrophy. Immunohistochemistry methods were used to identify
      the expression of connexin 43, proliferating cell nuclear antigen (PCNA) and
      cycline dependent kinases (cdc-2). The amount of connexin 43 expression was
      detected by computer imaging analysis system MIPS. RESULTS: In the groups which
      had PE or NE added, the myocytes expressed lower connexin 43 and higher PCNA
      levels than the control group's. But the expression of cdc-2 was unchanged.
      CONCLUSION: The reduced expression of connexin 43 was related to its entrance
      into S phase of the cell cycle. This may explain the mechanism of cardiomyocyte
      hypertrophy.

PMID- 11244956
TI  - [Progresses in the study of differential display analysis of gene expression].

PMID- 11244957
TI  - [The influence of Kupffer cells on experimental hepatocarcinogenesis].
AB  - OBJECTIVE: In order to explore the influence of Kupffer cells on experimental
      hepatocarcinogenesis. METHODS: A comparative study on the expression of
      proliferating cell nuclear antigen (PCNA), epidermal growth factor (EGF), ras
      P21, p53 protein and c-myc gene by means of immunohistochemistry or in situ
      hybridization during the diethylnitrosamine (DENA)-induced hepatocarcinogenesis
      performed in rats with and without pretreatment with gadolinium chloride (GC)
      which might effectively block the activity of Kupffer cells. RESULTS: There was
      no marked difference in the expression of PCNA and EGF in the liver tissue
      between the above two groups animals. The positive rate of ras P21 was markedly
      higher in the GC + DENA group than in the DENA group. The positive rate of p53
      protein in GC + DENA group was slightly higher than that of the DENA group,
      however, the appearance of expression was markedly earlier in the former group
      (in the 11th and the 19th week respectively). The expression intensity of c-myc
      gene was markedly higher in GC + DENA group that in DENA group. CONCLUSIONS: The
      results suggest that Kupffer cells can reduce hepatotoxicity induced by chemical
      carcinogen, and Kupffer cells may play an inhibitory effect on the process of
      hepatocarcinogenesis.

PMID- 11244958
TI  - [Influence of compensatory hepatocyte proliferation on the carcinogenesis of N
      nitrosodimethylamine].
AB  - OBJECTIVE: To study the influence of compensatory hepatocyte proliferation on the
      N-nitrosodimethylamine (NDMA) carcinogenesis in rats. METHODS: NDMA was given to
      animals of the experimental group 24 hours after partial hepatectomy, and the
      control group was only treated with NDMA. Expression of gamma-glutamyltransferase
      (GGT), glutathione S-transferase placental form (GSTP), proliferating cell
      nuclear antigen (PCNA), insulin-like growth factor-II (IGF-II) and oncogenes was
      detected. RESULTS: The numbers and areas of GGT- and GSTP-foci in the
      experimental group were significantly increased in comparing with the control
      groups. The expression of GSTP was higher than that of GGT. The total tumor
      incidence of the experimental group was higher than that of the control by the
      end of the 56th week. Up to week 71, the incidences of liver and other tumors
      were higher respectively in the experimental group. The amount of PCNA positive
      cells were corresponding with proliferative condition of the hepatic lesions. The
      expression of IGF-II, c-myc and H-ras mRNA increased in the altered hepatocyte
      foci and nodules, but markedly decreased in hepatocellular carcinoma and adenoma.
      No c-jun mRNA expression was detected in all the normal and abnormal tissues of
      liver. CONCLUSIONS: The results suggest that compensatory hepatocyte
      proliferation enhances the carcinogenesis induced by multiple doses of NDMA, and
      the over expression of IGF-II, c-myc, H-ras may play a synergetic role in NDMA
      induced hepatocarcinogenesis.

PMID- 11244959
TI  - [A study of gene expression of PDGFBB and PDGFR as well as level of PDGFR
      activity in human glioma cells].
AB  - OBJECTIVE: To investigate the effect of PDGFBB autocrine loop on the development
      and progression of human gliomas. METHODS: 73 human glioma specimens of different
      stages were studied using in situ hybridization and immunohistochemical
      techniques. RESULTS: 62 (84.9%) of 73 cases expressed PDGFB mRNA. The positive
      rate and the amount of PDGFB mRNA increased correspondingly with the degree of
      malignancy. All of 73 gliomas expressed PDGFR alpha, PDGFR beta and
      phosphotyrosine protein (P-Tyr). The positive cell densities of PDGFR alpha,
      PDGFR beta and P-Tyr correlated positively with one another and increased with
      the malignancy as well as the expression level of PDGFB mRNA in the gliomas.
      However, there was no significant difference between positive cell densities of
      PDGFR alpha and PDGFR beta in any glioma group with different grading.
      CONCLUSIONS: PDGFBB autocrine loop existed generally in the glioma cells, the
      expression levels of PDGFBB and PDGFRs were well correlated with the tumor
      grading and the positive cell density of P-Tyr which could objectively reflect
      the activity of PDGFRs and the signal pathways. It's suggested that abnormally
      increased activity of PDGFBB autocrine loop might play an important role in the
      development and progression of gliomas.

PMID- 11244960
TI  - [A pathological study on the autotransplantation of monkey's cervical sympathetic
      ganglion into brain for the treatment of Parkinson's disease].
AB  - OBJECTIVE: In order to find out evidences in explicating whether the transplanted
      ganglion cells can be kept surviving longer in the brain and to find out an ideal
      transplantation way for the surgical treatment of Parkinson's disease. METHODS:
      Cervical sympathetic ganglions autotransplantation into the caudate nuclei of the
      brain in 9 rhesus monkeys known to have the symptoms and signs of the Parkinson's
      disease beforehand induced by using 1-methy1-4-phen-1, 2, 3, 6-tetrahydropynidne
      (MPTP) and in addition, muscle tendon tissue was also grafted for comparison. The
      experimental animals were followed up for 2 years. All the specimens taken were
      processed and prepared in continuous frozen sections for H & E, glyoxlyic acid
      induced dopamine fluorescence and immunochemistry stainings including anti
      chromogranin A, synaptophysin, neurofilament, NSE, GFAP as markers. RESULTS: Two
      years after the autotransplantation operation, there were still surviving
      ganglion cells left in the caudate nuclei. The grafted ganglion cells were
      connected by the neurodendrites with the brain tissue which showed dopamine
      fluorescence positive and also had expression of chromogramin A, synaptophysin
      and neurofilaments. CONCLUSIONS: The grafted cells survived in the brain over 2
      years. It's considered that the sympathetic ganglion is the first choice in
      comparing with other tissues as the graft for the surgical treatment of
      Parkinson's disease. Continuous frozen sections accompanying with inducing
      fluorescence and immunohistochemistry staining are seemed reliable as the
      parameters in checking the result after neural transplantation.

PMID- 11244961
TI  - [Expression and mutation of p53 and H-ras genes in the carcinogenesis and
      development of gastric adenocarcinoma induced by MNNG in rats].
AB  - OBJECTIVE: To investigate the effect of p53 and H-ras genes in the carcinogenesis
      of and development of gastric cancer induced by N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG) in Wistar rats. METHODS: The expression of p53 and H-ras
      genes in normal mucosa, precancerous lesions and induced-cancers were studied
      immunohistochemically. DNA isolated from the precancerous lesion and tumors were
      analysed by PCR-SSCP for exon 5-8 of p53 gene and exon 1 and 2 of H-ras gene.
      RESULTS: p53 protein were detected in 50% (20/40) of the gastric cancers studied,
      but not in the precancerous lesion, while p21 ras protein seen in 23% (9/40) of
      the gastric cancers and 44% (23/52) of the precancerous lesions. p53 gene
      mutations were detected in 45% (18/40) of the cancers and none in the
      precancerous lesions by PCR-SSCP. H-ras gene mutation was not found in either the
      cancers or the precancerous lesions. CONCLUSIONS: The activation of ras gene is
      an early event and may be involved in the carcinogenesis of gastric cancer
      induced by MNNG. Inactivation of p53 gene may influence the development of the
      cancer.

PMID- 11244962
TI  - [Human tumor xenografted into SCID mice and human immune function
      reconstitution].
AB  - OBJECTIVE: In order to observe (1) The behavior of growth and metastasis of PG
      and PGPTS7 in SCID mice and human immune function reconstituted mice; (2) The
      ability of interleukin-6 autosecreted from PGTS7 in enhancing the anti-tumor
      activity of the peripheral blood lymphocytes (PBL). METHODS: Xenografting of PG
      and PGTS7 into the subepithelial space of the SCID mice, and in some of these
      animals, human PBL were administrated simultaneously into the peritoneal
      cavities. The latent period, taken rate, growth speed, volume of the grafted
      tumor, incidences of metastasis in lungs and lymph nodes and serum level of human
      immunoglobulin of the immunity reconstituted mice were examined. RESULTS:
      Although tumor growth had been detected in all the experimental animals, the
      latent period of grafted PGTS7 was postponed and the volume of tumor mass as well
      as the incidence of lymph node metastasis all became lower in the immunity
      reconstituted mice accompanied simultaneously with a higher serum level of human
      immunoglobulin (HIg). CONCLUSIONS: (1) The SCID mice are good as an appropriated
      hosts in studying the behavior of growth and metastasis of PG and PGTS7. (2) IL-6
      autosecreted from PGTS7 stimulates the proliferation and promotes the activating
      of PBL. It seems also able to enhance the liberation of human immunoglobulin: to
      suppress the growth of tumor cells and to reduced the rate of lymph node
      metastasis.

PMID- 11244963
TI  - [Detection of the p53 protein accumulation and p53 gene mutation in squamous cell
      carcinoma of the lung].
AB  - OBJECTIVE: To investigate the effects of p53 protein accumulation and p53 gene
      mutation in the pathogenesis of squamous cell carcinoma of lung. METHODS:
      Immunohistochemistry and PCR-SSCP techniques were used to detect p53 protein
      accumulation and p53 gene mutation. RESULTS: p53 protein accumulations was found
      in 52.5% (63/120) of the samples. p53 gene mutation was detected in 56.7%
      (68/120) of the same specimens by PCR-SSCP. In 24 cases (35.3%, 24/68), the
      mutations was locating on exon 5, 11 cases (16.2%, 11/68) on exon 6, 18 cases
      (26.5%, 18/68) on exon 7 and 15 cases (22.1%, 15/68) on exon 8 respectively. The
      rate of p53 gene mutation/overexpression was 60%. p53 gene
      mutation/overexpression rate of moderately (63.6%, 28/44) or poorly (63.5%,
      40/63) differentiated pulmonary squamous cell carcinoma was significantly higher
      than that of the well differentiated carcinoma (30.8%, 4/13). In comparing with
      non-lymph node metastasis group (43.1%, 28/65), p53 gene mutation/overexpression
      rate in metastasis group (80%, 44/55) was significantly higher. p53 gene
      mutation/overexpression rate of pulmonary squamous cell carcinoma in advanced
      stage (76.3%, 45/59) was significantly higher than that in the early stage
      (44.3%, 27/61). p53 gene mutation/overexpression rate in heavy smoking group
      (72.4%, 55/76) was significantly higher than that in non-smoking group (38.6%,
      17/44). No statistically significant correlation was found between p53 gene
      mutation/overexpression and sex, age, tumor location or invasion of the
      surrounding tissue. CONCLUSIONS: p53 gene mutation/overexpression may play an
      important role in the pathogenesis of squamous cell carcinoma of lung and can be
      considered as a predicting marker of prognosis.

PMID- 11244964
TI  - [Detection of MDM 2 and p 53 genes in rhabdomyosarcoma by in situ hybridization].
AB  - OBJECTIVE: To observe the correlation between MDM2, p53 genes and the
      pathogenesis, clinical pathology and prognosis in rhabdomyosarcoma (RMS).
      METHODS: Thirty one cases of MRS with follow-up history were covered for this
      study. MDM2 and p53 genes were detected by digoxigenin labeling in situ
      hybridization-technique. RESULTS: The positive rates for MDM2 and p53 genes were
      77.4% (24/31) and 66.7% (21/31) respectively, regardless of age, sex and the
      histological typing of RMS, but there was remarkable difference in the positive
      rates and intensity between the well and poorly differentiated cases, metastatic
      and non-metastatic cases as well as one year and three years survival period (P <
      0.05). CONCLUSIONS: The detection of MDM2 and p53 gene is considered valuable in
      evaluating the malignant degree, predictable metastasis and prognosis of RMS.

PMID- 11244965
TI  - [Neuroendocrine differentiation in ovarian mucinous tumors].
AB  - OBJECTIVE: To investigate the relationship between neuroendocrine differentiation
      of ovarian mucinous tumors and its genesis. METHODS: A morphologic study on 73
      cases of ovarian mucinous tumors (32 benign, 20 borderline, 21 malignant) using
      immunohistochemical and immunohistochemical/histochemical double staining
      techniques. RESULTS: The incidences of CgA positive cell in tumors of benign,
      borderline and malignant were 62.5%, 75%, 76% and that of 5-HT positive cells
      were 31.3%, 40%, 39% respectively. But these NEC were not evenly distributed. The
      interesting point was that in four cases of the benign tumors the number of CgA
      positive cell was more than 30 per cent localizing between the glandular basement
      membrane and the mucinous epithelial cells. There were also many intermediate
      cells containing both CgA and PAS positive granules. CONCLUSIONS: The positive
      rate of CgA was increased corresponding to the lowering down of differentiation
      grades. The four cases of the benign tumors might be originating from a common
      stem cell, such as so-called amphocrine cell. The relationship between these four
      tumors and neuroendocrine differentiation in ovarian mucinous tumors remain
      further clarified.

PMID- 11244966
TI  - [Matrix metalloproteinases and neoplasm invasiveness and metastasis].

PMID- 11244967
TI  - [Some critical points on current liver cancer research].

PMID- 11244968
TI  - [Relationship between oval cells and preneoplastic lesions induced by 2
      acetylaminofluorene in rat liver].
AB  - OBJECTIVE: To study the cellular origin of preneoplastic lesion of liver induced
      by the 2-acetylaminofluorene (2-AAF) in rat. METHODS: Male fisher 344 rats were
      used for two different carcinogenesis models. Model 1: Rats were fed with regular
      diet containing 0.02% 2-AAF for totally 28 days, and subjected to a standard two
      thirds partial hepatectomy (2/3 PH) on the 7th day in order to stimulate the
      proliferation of oval cells. 3H thymidine (3H-Tdr) was administered
      intraperitoneally on the 12th day for selective labelling of oval cells. Model
      II: Rats were subjected to 2/3 PH and 3H-Tdr was administered intraperitoneally
      22 hours after the operation for the selective labelling of hepatocytes. The rats
      were then fed with 2-AAF for totally 28 days after a 9 days recovery period from
      2/3 PH. The relationship between preneoplastic lesion and selectively labelled
      oval cells, or hepatocytes, was traced by autoradiography. RESULTS: Pathological
      examination and autoradiography denoted that the silver grains (labelled signals)
      were only formed in the preneoplastic cells in model I rather than the cells of
      model II animals. CONCLUSION: It is a direct evidence to demonstrate that the
      preneoplastic cells are mostly originated from the oval cells.

PMID- 11244969
TI  - [Study on telomerase activity in hepatocellular carcinoma and chronic hepatitic
      disease].
AB  - OBJECTIVE: To compare telomerase activity of hepatocellular carcinoma (HCC) with
      that of chronic liver disease to analyze the significance of telomerase activity
      in diagnosis of malignancy. METHODS: Telomerase activity was detected in 38 cases
      of HCC and corresponding non-tumor liver tissue with different chronic disease.
      That is 21 cases of hepatic cirrhosis, 2 cases of mild fibrosis, 2 cases of
      chronic viral hepatitis and 7 cases of non-tumor liver with no significant
      histopathological changes using TRAP assay. 4 cases of biliary atresia were also
      detected and 4 cases of normal liver tissue were the control. RESULTS: Telomerase
      activity was detected in 32 of 38 (86.8%) cases of HCC. Telomerase activity in
      HCC was not related with tumor cell differentiation types, tumor size and HBV
      infection, but expression of telomerase was highly correlated with serum alpha
      fetal protein (AFP) level of patients. Telomerase negative HCC group has
      statistically significant lower level of AFP (P < 0.01) when compared with
      telomerase positive HCC groups. Telomerase activity was not present in normal
      liver tissue (0/4), biliary atresia (0/4), mild fibrosis (0/2), chronic viral
      hepatitis (0/4) and no significant changes of non-tumor liver tissue (0/7). Weak
      telomerase activity was detected in 4 of 21 hepatic cirrhosis. CONCLUSION:
      Telomerase activity was only detected in most of HCC and few cases of hepatic
      cirrhosis, which may play a crucial role in hepatocarcinogenesis and may be
      useful for the diagnosis of malignancy.

PMID- 11244970
TI  - [Expression of integrin alpha 5, beta 1 subunit and fibronectin mRNAs in human
      hepatocellular carcinoma].
AB  - OBJECTIVE: To study the biologic significance of the expression of integrin alpha
      5, beta 1 subunit and fibronectin (FN) mRNAs in hepatocellular carcinoma (HCC).
      METHODS: Integrin alpha 5, beta 1 subunit and FN mRNAs were detected by using
      Northern blot (alpha-32P-labeled cDNA probes) and in situ hybridization (Dig
      labeled cDNA probes) in 15 cases of HCC, 5 cases of paracancerous cirrhotic liver
      and 3 cases of normal liver tissue. RESULTS: In well-differentiated HCC, the
      level of integrin alpha 5, beta 1 or FN mRNA expression was similar to those in
      normal liver and paracancerous cirrhotic liver tissues, but was markedly
      decreased, even absent in the poorly- and moderately-differentiated HCC tissues
      (P < 0.01, respectively). The expression of integrin alpha 5 and FN mRNAs was
      mainly detected in the cytoplasm of HCC cells. In all the HCC cases tested, the
      expression of integrin alpha 5, beta 1 and FN mRNAs was lower in 8 cases of HCC
      with focal invasion and/or intrahepatic metastasis than that in the others
      without invasion or metastasis(P < 0.05). In addition, the heterogeneous
      expression of FN mRNA was found in 5 cases of HCC with intrahepatic metastasis.
      CONCLUSIONS: Combined with the immunohistochemical observation before, it might
      be deduced that the changes of integrin alpha 5 beta 1 and FN protein expression
      in HCC tissues are because of changing of the mRNA levels related, which might
      deeply influence the cell differentiation, tumor invasion and metastasis of HCC.
      The appearance of the heterogeneous FN mRNA and its encoded FN protein might be
      associated with the development of HCC metastasis.

PMID- 11244971
TI  - [Perforin and Fas-ligand expression of tumor infiltrating lymphocytes in human
      hepatocellular carcinoma].
AB  - OBJECTIVE: To investigate perforin and Fas-ligand (Fas-L) expression of tumor
      infiltrating lymphocytes (TIL) in human hepatocellular carcinoma (HCC). METHODS:
      Expression of perforin and Fas-L of TIL was studied in 20 HCC cases using in situ
      hybridization and immunohistochemistry. RESULTS: Expression of perforin and Fas-L
      gene were detected in TIL in 80% of the cases studied. Among them, one patient
      (no. 14) in whom expression of perforin and Fas-L were noticed in the majority of
      the TIL, had no recurrence of HCC for one and one half (1.5) year after tumor
      resection. It indicates that presence of large number of activated T cells might
      be beneficial for the tumor therapy. In the remaining cases, only 10% of TIL were
      obtained able to express perforin and Fas-L indicating that only a few TIL were
      activated and cytotoxic to HCC. CONCLUSIONS: Even there were a multitude of T
      cells infiltrating in HCC, only few of them were immunoactived and to be
      cytotoxic to HCC. It seems important to adopt measures in order to promote
      further proliferation of these activated T cells either in vitro or in vivo.

PMID- 11244972
TI  - [Pathology is capable of providing more scientific basis for further improving
      the prevention and treatment of coronary heart disease].

PMID- 11244973
TI  - [Morphologic discrepancies of coronary atherosclerotic lesions between patients
      with stable and unstable angina plus acute myocardial infarction].
AB  - OBJECTIVE: To compare the morphological difference of coronary atherosclerotic
      plaques in patients with stable angina(SA), unstable angina (UA) and acute
      myocardial infarction (AMI). METHODS: 101 autopsy cases of patients with SA, UA
      and/or AMI were studied using routine histological and immunohistochemical
      staining. RESULTS: Coronary atherosclerotic plaques in SA patients were mainly
      the fibrous plaques with no or just very small necrotic cores; rich in smooth
      muscle cells and collagen fibers, less foamy cells (stable plaque), low incidence
      of plaque rupture (14% only) and no thrombosis found. The atherosclerotic plaques
      in UA and AMI patients were mainly the atheroma (unstable plaque) with large
      necrotic core (> 40%), thin fibrous cap, less smooth muscle cells and abundant
      foamy cells. The incidences of plaque rupture were 76% and 82%, thrombosis 81%
      and 91% respectively in 58 cases of UA and 22 cases of AMI, and the incidence of
      UA is statistically significant in comparing with that of the SA group (P <
      0.001). CONCLUSION: In SA group, stable plaque was the main finding, plaque
      rupture and thrombosis rare. While in UA and AMI patients, unstable plaques
      predominant with a high incidence of plaque rupture and thrombosis which were the
      leading cause of acute coronary events.

PMID- 11244974
TI  - [The role of apolipoprotein A-I in the very early stage of experimental
      hyperlipidemia].
AB  - OBJECTIVE: To find out the change of serum total cholesterol, HDL cholesterol,
      LCAT activity, and the expression of apoA-I mRNA in liver and intestine in the
      very early stage of experimental hyperlipidemia of rabbits. METHODS: Experimental
      hyperlipidemia models were established by cholesterol feeding in NZW rabbits.
      Animals of the experimental groups were sacrificed by the end of the 1st, 2nd,
      4th and 7th week respectively. Serum total cholesterol (TC), free cholesterol
      (FC), LCAT activity, HDL were assayed. Slot blot were used to analyze the
      expression of apoA-I mRNA in liver and intestine. RESULTS: TC and FC were noticed
      to be elevated at the end of the 1st week after cholesterol feeding. The increase
      of LCAT activity was proportional to the levels of serum lipid. Serum HDL-C level
      did not drop down by the 7th week of cholesterol feeding. Analysis of lipid
      infiltration area in aorta of the experimental group rabbits showed apparent
      lipid disposition in intima since the 4th week of cholesterol feeding. Slot blot
      results showed that apoA-I mRNA level increased at the end of the 1st week in the
      small intestine. The expression in liver was much weaker than in intestine.
      CONCLUSION: In the very early stage of experimental hyperlipidemia, serum TC, FC,
      LCAT activity increase remarkably and apoA-I, mainly produced in the small
      intestine, plays an important role in activating LCAT.

PMID- 11244975
TI  - [Effects of oxidatively modified lipoproteins on the expression of monocyte
      chemoattractant protein-1 in endothelial cells].
AB  - OBJECTIVE: To clarify whether lipoproteins, particularly oxidatively modified low
      density lipoprotein (OX-LDL) and very low density lipoprotein (OX-VLDL) play a
      role in the express of monocyte chemoattractant protein-1 (MCP-1) mRNA and
      protein in endothelial cells (ECs). METHODS: After a 24-hour exposure to LDL, OX
      LDL, VLDL and OX-VLDL respectively the total RNA in call aorta ECs was extracted
      by means of guanidinium isothiocyanate method. MCP-1 mRNA expression in ECs was
      examined by dot blot analysis using a gamma-32P-end-labelled 35 mer
      oligonucleotide probe of MCP-1. Meanwhile, MCP-1 protein in EC conditioned media
      (EC-CM) of each group was determined by sandwich ELISA, and MCP-1 protein in ECs
      was examined immunocytochemically as well. RESULTS: Cultured calf aorta ECs
      expressed MCP-1 mRNA and protein, and OX-LDL and OX-VLDL induced further a strong
      expression of MCP-1 mRNA, and an increased MCP-1 protein level in EC-CM. The
      expression of MCP-1 mRNA and protein was only slightly increased when exposed to
      LDL and VLDL, and immunohistological staining with polyclonal MCP-1 antibody give
      a similar result. CONCLUSION: OX-LDL and OX-VLDL are able to induce a strong
      expression of MCP-1 in ECs.

PMID- 11244976
TI  - [The dynamic change of extracellular matrix in human coronary atherogenesis].
AB  - OBJECTIVE: To investigate the expression of type I, III procollagen mRNAs and
      chondroitin sulfate proteoglycan (CSPG) genes, as well as the distribution of
      type I, III collagen fibers and CSPG in human coronary atherogenesis. METHODS:
      Staining for HE, picrosirius red, immunohistochemistry and hybridization in situ
      technique were included. RESULTS: (1) Along with the development of
      atherosclerotic lesion, collagen type I, III and CSPG were increased
      simultaneously in the coronary wall; The expressions of type I, III procollagen,
      biglycan, and decorin mRNAs were noticed to be increased in the plaques. (2) beta
      lipoprotein was seen coexistently with CSPG in the AS plaques of the coronary
      arteries. (3) There were more SMC proliferation, predominant augmentation of type
      III collagen fibers and accumulation of CSPG in the early plaques of most young
      subjects; but less SMC, amount of type I collagen fibers and deposition of CSPG
      in the advanced plaques of most aged people. CONCLUSION: Over-expression of type
      I, III procollagen, biglycan and decorin mRNAs was related to the increase of
      type I, III collagen and CSPG in the atherosclerotic lesions. Proliferation of
      SMC, augmentation of type I, III collagen and CSPG and change of the proportion
      between collagen and CSPG are considered to play an important role in the
      development of coronary atherosclerosis.

PMID- 11244977
TI  - [The role of mast cells in myocardial fibrosis in SHRsp].
AB  - OBJECTIVE: To study the role of mast cells in hypertensive myocardial fibrosis.
      METHODS: The myocardial collagen and the degree of myocardial fibrosis were
      assessed using Masson's trichrome staining and image analysis plus toluidine blue
      as well as proliferating cell nuclear antigen (PCNA) staining and transmission
      electronic microscopy for SHRsp, aged 34 weeks (S group, n = 6). Besides, age and
      sex-matched WKY (W group, n = 5) were used as the controls. RESULTS: MC count
      increased 3.9 folds and PCNA immunostaining positive cells (PCNAP) increased 3.9
      fold (both P < 0.0001) in S vs W group. MC were positively correlated with the
      interstitial collagen volume fraction (ICVF), perivascular collagen area/vascular
      lumenal cross area (PVCA/VLCA), and PCNAP (r = 0.47, P < 0.05; 0.59, P < 0.001;
      0.68, P < 0.001 respectively). Electromicroscopy showed specific piecemeal
      degranulation of the mast cells, locating between the praliferative interstitial
      collagen fibers. CONCLUSION: The findings suggested that MCs play a role in
      certain degree to the myocardial fibrosis present in SHRsp.

PMID- 11244978
TI  - [Correlation of serum markers with fibrosis staging in chronic viral hepatitis].
AB  - OBJECTIVE: To assess the correlation between serological fibrosis markers and
      staging of fibrosis in chronic hepatitis. METHODS: One hundred and fourteen (114)
      biopsy and 13 autopay liver specimen were reviewed pathohistologically. Serum
      samples for liver function tests and fibrosis marker assays including serum P-III
      P, IV collagen, laminin (LN), hyaluronic acid (HA), h-TIMP-1 were collected
      simultaneously right before the biopsy or autopsy. HE, sirius red stains as well
      as staining for reticulum and elastic fiber were done. In besides, IV collagen,
      laminin, activated stellate cell were assayed by immunohistochemical methods.
      RESULTS: Among 127 patients, 92 cases of chronic viral hepatitis including early
      cirrhosis and 18 cases of hepatic cirrhosis were examined pathologically (17
      alcoholic liver disease excluded). The overall inflammatory index and fibrotic
      scoring were noticed to be significantly correlated with each other (r = 0.82, p
      < 0.01); The markers, such as HA, P-III-P, LN, IV collagen, h-TIMP-1 were
      positively correlated with the fibrotic staging and scoring (r = 0.610, 0.575,
      0.607, 0.641, 0.606 respectively). The higher the marker level, the more serious
      the fibrotic change. In addition, (18 cases) patients with active cirrhosis (16
      cases) showed higher serum marker level than that of the early cirrhosis and the
      serum markers in the later were higher than that in the non-active cirrhosis.
      CONCLUSION: Serum fibrosis markers are fairly well correlated with the staging of
      fibrosis and are considered to be the valuable references for clinical diagnosis.
      The close correlation between inflammation process and fibrosis suggests that the
      inflammatory process plays an important role in fibrogenesis.

PMID- 11244980
TI  - [Apoptosis induced by adenovirus-mediated wild-type p53 expression in human
      pancreatic cancer cells].
AB  - OBJECTIVE: To investigate the biological effects of wtp53 expression on the
      growth rate and apoptosis of human pancreatic carcinoma. METHODS: The Ad5CMVwtp53
      a recombinant replication-deficient adenoviral vector containing a human CMV
      promoter, a human wild-type p53 and the SV40 polyadenylation signal was amplified
      in 293 packaging cells. The pancreatic carcinoma cell line (PC-2), carrying a
      mutation of p53 gene at codon 240, was transfected using Ad5CMV wtp53 and the
      control adenoviral vector Ad5pXJ. RESULTS: The cells transfected with Ad5CMV
      wtp53 showed that presence and expression of wtp53 gene were demonstrated using
      PCR and immunoprecipitation, that growth rate and 3H-TdR incorporation rate were
      decreased. The restoration of wtp53 encoded protein in PC-2 cells induced
      apoptosis assessed by in situ TUNEL apoptosis, flow cytometry, DNA agarose gel
      electrophoresis analyses, whereas noninfected cells or the cells infected with
      control virus didn't show these changes. CONCLUSION: Replication-deficient
      adenoviral vector is an efficient vector in transferring wtp53 gene and antitumor
      therapy using the p53 gene is a valuable method in inhibiting pancreatic cancer
      cells growth by inducing apoptosis.

PMID- 11244981
TI  - [Detection of T-cell receptor gamma chain gene rearrangement in midline T-cell
      lymphomas by PCR method].
AB  - OBJECTIVE: To investigate the clonality of midline T-cell lymphoma. METHODS:
      Using polymerase chain reaction method and a panel of family specific primers for
      the variable regions of TCR-gamma gene, and totally 11 cases (22 samples) of
      midline T-cell lymphoma (midline malignant reticulosis) were studied. RESULTS:
      Family specific monoclonal TCR-gamma gene rearrangements were found in 21 out of
      22 samples (94.45%). There was no change of clonality during the course of
      disease. CONCLUSION: There is monoclonal T-cell proliferation in midline T-cell
      lymphoma and the clonality is not transformed with the advance of the disease.
      This finding provides an evidence to support the hypothesis of monoclonal origin
      of neoplasm.

PMID- 11244979
TI  - [The characteristics and significance of oncogenes expression in oval cells
      cultivated in vitro].
AB  - OBJECTIVE: To study the relationship between expression characteristics of
      oncogenes and transformation of the oval cells cultivated in vitro. METHODS:
      Liver oval cells of SD rats induced by feeding with chemical carcinogen 3'-Me-DAB
      for four weeks were isolated using Percoll density gradient centrifugation. The
      cells were continuously cultivated in vitro and the dynamic characteristics of Ha
      ras, Ki-ras and c-myc genes expression in the oval cells were detected using RNA
      DNA slot blot hybridization. RESULTS: During long term cultivation, the
      population doubling time of the cells became shorter and the percentage of
      aneuploidy chromosomes and colonies grown in soft agar increased. Ha-ras Ki-ras
      and c-myc were synchronically expressed in the oval cells from different
      passages. CONCLUSION: The activation and synergistic over-expression of Ha-ras Ki
      ras and c-myc had an important role in the proliferation and transformation of
      oval cells in vitro.

PMID- 11244982
TI  - [Correlation between human papillomavirus type and grading of cervical
      intraepithelial neoplasia].
AB  - OBJECTIVE: To disclose the correlation between human papillomavirus (HPV) type
      and grade of cervical intraepithelial lesion (CIN). METHODS: PCR and in situ
      hybridization (ISH) techniques were used to detect the presence of HPV 6B/11, 16,
      18 in 61 cases of CIN and 12 cases of cervical squamous cell carcinoma (SCC).
      RESULTS: PCR showed HPV 6, 11 distributing mainly in low-grade squamous
      intraepithelial lesion (LSIL, 61.9%) and partly in CINII (20%), but not in CINIII
      and SCC. The frequency of HPV 16, 18 increased corresponding to the increasing of
      CIN grading and up to 83.3% in SCC. ISH showed HPV 6b/11, 16, 18 DNA
      hybridization intranuclear signal were diffusely distributed in LSIL and granular
      in appearance in episomal HPV. Similar signal were also seen in CINII infected by
      HPV 6b/11 and partly by HPV 16, 18, anyhow, CINIII, SCC and partly CINII HPV 16,
      18 DNA hybridization were nongranular in appearance. CONCLUSION: low-grade SIL
      associated with "low-risk" types of HPV 6, 11 belonged to productive infection.
      CINIII and SCC associated with "high-risk" types of HPV 16, 18 belonged to
      integrated infection, while CINII belonged to either productive or integrated
      infection.

PMID- 11244983
TI  - [The role of cytokeratin 7 in the differential diagnosis of primary ovarian
      carcinoma and metastatic ovarian carcinoma originated from the gastrointestinal
      tract].
AB  - OBJECTIVE: To assess the role of cytokeratin 7 monoclonal antibody in the
      differential diagnosis of primary ovarian carcinoma and metastatic ovarian
      carcinoma originated from the gastrointestinal tract. METHODS:
      Immunohistochemical study using cytokeratin 7 monoclonal antibody and ABC kit.
      RESULTS: All the 46 cases of primary ovarian carcinoma were CK 7 positive, while
      in the metastatic ovarian carcinoma of intestinal origin, all cases remained
      negative for CK7. Half of the 34 cases of metastatic ovarian carcinoma of gastric
      origin were CK 7 positive. The positive result of CK7 was significantly higher in
      the primary ovarian carcinoma than in each group of the metastatic ovarian
      carcinoma (P < 0.001). CONCLUSION: CK 7 is seemed to be a useful antibody in the
      differential diagnosis of ovarian carcinoma.

PMID- 11244984
TI  - [Pathological characteristics of gonads in nine patients with true
      hermaphroditism].
AB  - OBJECTIVE: To investigate the gonadal histopathology of true hermaphroditism and
      its correlation with the clinical features. METHODS: Clinico-pathological
      materials and chromosomal karyotypes from 9 true hermaphroditisms were reviewed.
      RESULTS: Seven out of 9 patients aged 5-21 years had been raised as females, and
      the other two were raised as males. Ovotestis was the most common form of the
      abnormal gonads, 2 out of 9 patients had bilateral ovotestes, 7 had unilateral
      ovotestes (5 in right side, 2 in left side). In the 7 patients with unilateral
      ovotestis, 6 had a contralateral ovary and one had a contralateral testis.
      Microscopically, the ovarian tissue of 11 ovotestes, including 6 biopsies from
      contralateral ovaries were normal, with many primordial follicles and a few
      growing follicles. In two of the patients, aged over 15 years, evidence of
      ovulation was observed. In comparison, the testicular tissue of the ovotestis and
      one left inguinal testis was histologically abnormal. Two of the 9 patients
      conceived and delivered normal infants by cesarean section after surgical
      treatment. CONCLUSION: Identification of the gonadal histopathology in these
      cases is important in order to make a correct scheme for the treatment.

PMID- 11244985
TI  - [A clinical and pathological study of cerebellar medulloblastoma in adult
      patients].
AB  - OBJECTIVE: In order to study the clinicopathological characteristics,
      histogenesis and prognosis of medulloblastoma in the adult patients. METHODS:
      Altogether 27 patients of medulloblastoma admitted form 1974-1995 were reviewed.
      RESULTS: In all of the cases, age ranged from 16 to 55, (average 25.8 years) with
      21 tumors localized in the cerebellar vermis, and 6 tumors in the cerebellum.
      Among them, 12 cases were completely while 14 cases were subtotally removed and
      biopsy was done in only one case. In the 21 patients to be followed up, 7
      survived for 2.5-17 years after the operation, and 14 died. The average survival
      period was 41.6 months. One year survival rate was 71.4%, five years and ten
      years survival rates were 14.3% respectively. Regarding to the histological
      types, 14 cases were considered to be classic and 13 cases were desmoplastic by
      histological classification. CONCLUSION: Medulloblastoma keeps still the ability
      of differentiation to neurons and astrocytes confirmed by electronmicroscopy and
      immunohistochemical staining for Syn, NSE and GFAP. Factors considered
      responsible to the prognosis included age, tumor location, various therapeutic
      measurements and the histological classification.

PMID- 11244986
TI  - [Preparation and identification of monoclonal antibodies to estrogen and
      progesterone receptors].
AB  - OBJECTIVE: Preparation of anti human progesterone receptor (PR) and estrogen
      receptor (ER) monoclonal antibodies (McAb). METHODS: Characterization of the two
      McAbs were detected by Western blot, immunohistochemical, immunofluorescence and
      fluocytometer techniques. RESULTS: (1) A specific protein belt was obtained
      between anti-PR McAb and the extract of cell line T47D and the same result was
      noticed between anti-ER McAb and extract from MCF-7 cell line by Western blot.
      (2) The PR and ER status of 40 and 35 human breast cancer were studied by
      immunohistochemistry (IHC) using the anti-PR and ER McAb. The efficacy of the
      McAbs prepared was just the same as that of the McAbs purchased from Zymed
      company. The corresponding rate of determination for ER and PR status between IHC
      and DCC were 85% and 91.4%, respectively. (3) The fluorescent markers were mainly
      localized in the cell nuclei when detected through indirect immunofluorescence
      techniques. (4)FCM showed that fluorescent index was larger than 1.0, and
      negative control F1 was less than 1.0. CONCLUSION: The anti-PR and ER McAbs
      prepared in this program are specific and sensitive and have the similar efficacy
      and quality as the Zymed PR and ER McAbs.

PMID- 11244987
TI  - [Advances in the study of peptide nucleic acids].

PMID- 11244988
TI  - [Progress in pathological diagnosis of lymphoma].

PMID- 11244989
TI  - [Expression of cytotoxic-granule-associated protein TIA-1 in nasal NK/T cell
      lymphomas and lymphoid hyperplasia].
AB  - OBJECTIVE: 27 cases of nasal NK/T cell lymphomas were studied for the expression
      of the cytotoxic-granule-associated protein TIA-1, its immunophenotype, genotype
      and Epstein-Barr virus infection status. METHODS: Immunohistochemical staining
      for TIA-1, CD3, CD56, CD45RO, CD8, CD20; polymerase chain reaction (PCR) for TCR
      gamma chain gene and immunoglobulin JH chain gene rearrangement analysis; in situ
      hybridization for EBER 1/2 and double staining for TIA-1, CD8 with EBER 1/2. 10
      cases of lymphoid hyperplasia were used for comparison. RESULTS: (1) In the 27
      cases of nasal NK/T cell lymphomas, most tumor cells expressed TIA-1, CD3, CD45RO
      and EBER 1/2; expression of CD56 was found in 26 cases; no CD8 or CD20 were
      detected in tumors cells of this series of cases. Double labelled staining showed
      that the TIA-1 positive tumor cells coexpress EBER 1/2. TCR gamma chain gene
      rearrangement was detected in only 1 of the 27 cases. (2) In the 10 cases of
      lymphoid hyperplasia of nasal pharynx, a small amount of TIA-1 positive cells
      were present in 8 cases and their distribution similar to that of CD8+ cells, in
      4 of these cases a few EBER 1/2+ cells were detected, the number of CD45RO+ cells
      and CD20+ cells were similar in all 10 cases. Double labelled staining showed
      that the EBER 1/2+ cells did not coexpress TIA-1. CONCLUSION: A high percentage
      of these tumor cells express TIA-1 and correlate with that of CD56, CD3 epsilon,
      CD45RO and EBER1/2 in nasal NK/T cell lymphomas. It is suggested that expression
      of TIA-1 in this tumor may be related to the tumor origin and may also be
      responsible for its special biologic behavior.

PMID- 11244990
TI  - [Investigation of the clinicopathologic features, immunophenotype and Epstein
      Barr virus infection of the upper respiratory tract lymphomas in patients].
AB  - OBJECTIVE: To study the clinicopathologic features, immunophenotype and Epstein
      Barr virus (EBV) infection of the upper respiratory tract lymphomas in patients
      from north China. METHODS: 112 cases of upper respiratory tract lymphomas in
      patients from north China were investigated. HE stain for histologic features.
      Immunohistochemistry studies were performed using monoclonal antibodies, UCHL-1
      for T-lymphocyte, L26 and 4KB5 for B lymphocyte, CS1-4 for latent membrane
      protein-1 (LMP-1). In situ hybridization for EBV encoded small nuclear RNA (EBER
      1/2, Y017, DAKO). RESULTS: 77/112 cases (68.75%) were T-cell lymphomas, 35 cases
      (31.25%) were B cell lymphomas. EBV-EBER 1/2 in situ hybridization positive in
      54/101 (53.46%) cases, including 48 T-cell lymphoma cases and 6 B-cell lymphoma
      cases. CONCLUSION: Most upper respiratory tract lymphoma cases in patients from
      north China are T-cell lymphomas and are strongly associated with EBV.

PMID- 11244991
TI  - [Detection of Epstein-Barr virus subtypes in Hodgkin's disease].
AB  - OBJECTIVE: To investigate Epstein-Barr virus (EBV) subtypes in Chinese patients
      with Hodgkin's disease (HD). METHODS: 113 cases of HD patients with EBV latent
      membrane protein 1 (LMP-1) and/or EBV encoded small RAN (EBER-1) positive and
      throat washings from 21 healthy persons were studied for EBV subtypes by
      polymerase chain reaction (PCR). RESULTS: 68 HD cases exhibited specific bands,
      in which 62 cases were EBV type A and 6 cases were EBV type B. 13 of the control
      washing gave rise to specific bands, of which 11 were EBV type A and 2 of EBV
      type B. CONCLUSION: The results showed that EBV type A is predominant in Chinese
      HD patients and healthy individuals.

PMID- 11244992
TI  - [The correlation between Burkitt's lymphoma and Epstein-Barr virus in 28 cases
      and their expression of p53 and bcl-2 proteins].
AB  - OBJECTIVE: To investigate the correlation between Burkitt's lymphoma and Epstein
      Barr (EB) virus and its expression of p53 and bcl-2 proteins. METHODS: Polymerase
      chain reaction (PCR), in situ PCR and immunohistochemical techniques were applied
      to specimens from 28 cases of Burkitt's lymphomas on paraffin-embedded sections.
      RESULTS: EB virus was found in 8 (28.5%) cases by PCR, of which 3 were positive
      by in situ PCR. Positive rates for the expression of p53 and bcl-2 were 44.4% and
      48.1% respectively. Whereas in stages I-II and III-IV, they were 3(23.0%),
      9(64.2%) and 3(23.0%), 10(71.4%) respectively. Both the expression of p53 and bcl
      2 were high in stages III-IV, low in stages I-II (P < 0.05). The positive cases
      of EB virus in combination with the expression of p53 and bcl-2 protein, p53
      protein and bcl-2 protein were 4,5,4 respectively and 9 cases were positive for
      p53 and bcl-2 protein. In other words, the positive cases for EB virus in
      combination with the expression of p53 and bcl-2 were 50%, whereas 70% were
      positive for both p53 and bcl-2. CONCLUSIONS: The positive rates of EB virus in
      our series are different from some reports of African-Burkitt's and similar to
      many other reports of endemic Burkitt's lymphoma. The expression of p53 and bcl-2
      proteins are significantly correlated with stage; high in stages III-IV and low
      in stages I-II. EB virus, p53 and bcl-2 proteins may affect each other.

PMID- 11244993
TI  - [The detection of CD56 in T-cell lymphoma and its relationship with Epstein-Barr
      virus].
AB  - OBJECTIVE: To investigate the expression of CD56 and the relationship between
      CD56 positive expression and EBV infection in T-cell lymphoma (TCL) in Guangdong
      province. METHODS: Immunohistochemistry was used to detect CD56 and in situ
      hybridization was used to detect EBER in 46 cases of TCL. RESULTS: (1) 17.4%
      (8/46) TCL were CD56 positive. According to the site of origin, the TCL
      originated from the nose, pharynx and oral cavity had the highest CD56 positive
      rate (5/17, 29.4%). Anyhow, according to the type pattern, the diffuse large cell
      lymphoma had the highest CD56 positive rate (6/16, 37.5%). (2) 52.2% (24/46) of
      the TCl were EBER positive. (3) 4/8 cases of the CD56 positive TCl expressed
      EBER. CONCLUSION: The findings suggest that the expression of CD56 in TCL was
      possibly related to original sites and TCL subtypes. EBV infection was not
      related to CD56 positive TCL in this study.

PMID- 11244994
TI  - [Hodgkin's disease: Ig gene rearrangements in single H/R-s cells].
AB  - OBJECTIVE: To investigate the origin and cell lineage of Hodgkin/Reed-Sternberg
      (H/R-S) cells from various subtypes of Hodgkin's disease (HD). METHODS: 68 single
      H/R-S cells were taken from frozen section of 8 cases of HD. The DNA from these
      single cells was amplified by polymerase chain reaction (PCR) with immunoglobulin
      heavy chain gene FR III a/JH primers and light chain family-specific primers.
      RESULTS: (1) IgH and V kappa 4 rearrangements were repeatedly found in H/R-S
      cells from one case of lymphocytic predominant HD (LPHD). (2) Repeated and unique
      IgH and V kappa 2,4 rearrangements were observed in 1 case of nodular sclerosing
      HD (NSHD) and unique IgH, V lambda 3/V kappa 4 rearrangements in another case of
      NSHD. (3) Repeated IgH/V lambda 3 and unique V lambda 2,4 rearrangements,
      repeated V kappa 4 and unique IgH/V kappa 3 rearrangements, plus repeated IgH and
      unique V kappa 3/V lambda 4 rearrangements were detected respectively in 3 cases
      of mixed cellularity HD (MCHD). Repeated and unique rearrangements were found
      respectively in 2 cases of MCHD. CONCLUSIONS: The H/R-S cells isolated from LPHD
      had monoclonal Igh and V kappa 4 gene rearrangements, which supports the
      conclusion that LPHD is a monoclonal proliferation of B cells. The appearance of
      IgH and kappa, lambda gene rearrangement suggest that the H/R-S cells isolated
      from classical HD (MCHD and NSHD) originate from B lineage cells at various
      stages of differentiation.

PMID- 11244995
TI  - [The relationship between HBV infection and injury of tubuli and interstitium in
      IgA nephropathy].
AB  - OBJECTIVE: To clarify the correlation between HBV infection and the injury of
      tubuli and interstitium of IgA nephropathy. METHODS: Renal biopsy specimens from
      91 patients with primary IgA nephropathy were investigated by use of in situ
      hybridization (HBV DNA), immunohistochemistry (HBsAg, HBcAg, CD3, CD8) and HBV
      DNA, HBAg-CD43 double staining techniques. RESULTS: The positive rate of HBAg in
      renal tissue as detected by immunohistochemistry was 69.2% and that of HBV DNA
      detected by in situ hybridization was 42.9%. Double staining showed that HBV DNA
      positive tubular epithelial cells might coexpress HBsAg and/or HBcAg. The numbers
      of the infiltrated CD3+ cells and CD8+ cells in cases with positive HBV
      infections markers were significantly higher than those of cases without
      infection (P < 0.01). In addition, CD43+ T lymphocytes infiltrated around or
      invaded into the tubuli walls which had positive HBcAg or HBsAg expression.
      CONCLUSION: After HBV infection, the renal cells could express HBAg and induce
      infiltration of CD3+ cells and CD8+ cells, resulting in aggravation of the injury
      of tubuli and interstitium. Therefore, it is considered that HBV infection might
      play an important role in the occurrence and progress of IgA nephropathy.

PMID- 11244996
TI  - [Expression of CD44V6 and its effects on cytoskeleton in human colorectal
      carcinoma cell lines].
AB  - OBJECTIVE: To observe the expression of CD44V6 and its effects on cytoskeleton in
      human colorectal carcinoma(HCC) HT29 and LoVo cell lines. METHODS: Expression of
      CD44V6 variant in HCC HT29 and LoVo cell lines was investigated by in situ
      hybridization, immunohistochemistry and quantitative immunofluorescence
      technique. The effects of CD44V6 variants on cytoskeleton was studied by
      immunofluorescence and confocal 3 dimension reconstruction technique. RESULTS:
      CD44V6 was expressed at the mRNA and protein levels in both HT29 and LoVo cell
      lines, but the expression was higher in LoVo cells than in HT29 cells. When the
      HT29 cells and LoVo cells were blocked by monoclonal antibodies, it was found
      that changes developed in the cytoskeleton of these cells. CONCLUSIONS: The
      expression of CD44V6 is related to the metastatic potentiality of human
      colorectal carcinoma cells. CD44V6 may affect the distribution, polymerization
      and depolymerization of actin of HCC cells and promote HCC cell metastasis.

PMID- 11244997
TI  - [The relationship of vascular endothelial growth factor and angiogenesis to the
      progression of gastric carcinoma].
AB  - OBJECTIVE: To investigate the relationship of vascular endothelial growth factor
      (VEGF) and angiogenesis to the progression of gastric carcinoma (GC). METHODS:
      VEGF protein expression and microvessel density (MVD) in 56 cases of human GC and
      VEGF mRNA expression in some cases were examined by use of immunohistochemical
      staining and in situ hybridization technique respectively. MVD and VEGF
      expression were analysed together with their relation to histologic types, depth
      of invasion, growth pattern, lymph node metastasis, distant metastasis and
      relapsing rate of GC. RESULTS: MVD was significantly higher in VEGF-positive GC
      than in VEGF-negative GC (P < 0.01). MVD and VEGF positively correlated with
      depth of invasion (P < 0.01), lymph node metastasis (P < 0.05) and distant
      metastasis (P < 0.05), but their relation to the histologic types and growth
      pattern of GC was not significant. The 5 year survival rate was significantly
      lower in GC patients with positive expression of VEGF or with MVD > or = 43. The
      expression of VEGF mRNA was consistent with that of VEGF protein, but the
      distribution is different. CONCLUSION: VEGF is highly related to angiogenesis of
      GC and promotes growth, invasion and metastasis of GC. VEGF expression or MVD is
      one of the predictors for the biological behavior of GC.

PMID- 11244998
TI  - [A clinicopathological analysis of primitive neuroectodermal tumors of the CNS].
AB  - OBJECTIVE: To investigate the difference between cerebellar medulloblastoma (MB)
      and primary cerebral small cell tumor in histogenesis, morphologic features and
      biological behavior. METHODS: 210 cases of MB and 9 cases of small cell tumor of
      cerebrum were observed with histologic and immunohistochemical techniques.
      RESULTS: Both tumors were composed of primitive cells with focal evidence of
      glial and/or neuronal differentiation. In 63.2% of MB and five-eighths of small
      cell tumor of cerebrum coexpressed GFAP and Syn. Both types of tumors were highly
      malignant. The overall 1 year survival rates were 34.63% and 25.65% respectively.
      The survival rate was lower for patients with high proliferative index, with
      necrosis or without receiving radiation therapy. CONCLUSION: MB is similar to
      other small cell tumors of CNS in morphological features, specific marker
      expression and biological behavior. These tumors can be classified as primitive
      neuro-ectodermal tumors (PNET).

PMID- 11245000
TI  - [A study of p16 gene and its protein expression in rhabdomyosarcoma].
AB  - OBJECTIVE: To evaluate the relationship between alteration of p16 gene, its
      protein expression and the pathogenesis and development of rhabdomyosarcoma
      (RMS). METHODS: 44 cases of RMS were examined for alteration of p16 gene with PCR
      SSCP and 47 cases of RMS were examined for p16 protein expression with
      immunohistochemical method. RESULTS: The homozygous deletion of p16 gene was
      observed in 2 cases and mutations in 6 cases. Of these 8 cases with altered p16
      gene, 6 had extensive invasion, recurrence or metastasis. The total negative rate
      of p16 protein expression in RMS was 38.3% (18/47 cases). Of these 8 cases with
      alterations of p16 gene, negative expression for p16 protein was observed in 7
      cases and positive in only 1 cases. In contrast, no structural abnormalities of
      the p16 gene were detected in another 11 cases with negative expression of p16
      protein. Higher rates of p16 gene abnormality and loss of p16 protein were
      observed in ARMS than in ERMS. Higher rate of extensive invasion, recurrence or
      metastasis was also found in the group negative for p16 protein. CONCLUSION: The
      abnormalities of p16 gene and loss of p16 protein expression may be related to
      the pathogenesis and development of some RMS.

PMID- 11244999
TI  - [p53 alterations in human lung cancer and their correlation with
      clinicopathological features and prognosis].
AB  - OBJECTIVE: To investigate p53 protein accumulations and p53 mutations in squamous
      cell carcinoma and adenocarcinoma of the lung and their correlation with
      clinicopathological features and prognosis. METHODS: Immunohistochemistry (LSAB)
      and non-isotopic PCR-SSCP were used to detect p53 abnormalities in lung cancer.
      RESULTS: The general positive rates for immunohistochemistry using anti-p53
      monoclonal antibody Do-7 (DAKO) as first antibody was 50.5% in 95 cases of lung
      cancer, 56.5% (26/46) in squamous cell carcinoma and 44.9% (22/49) in
      adenocarcinoma. PCR-SSCP results showed that 39 cases (41.1%) showed abnormal
      bands. The mutation rate in squamous cell carcinoma was 47.8% (22/46) and 34.7%
      (17/49) in adenocarcinoma. In 15 (38.5%) cases, the mutations were located on
      exon 5, 3 (7.7%) were on exon 6, 13 (33.3%) on exon 7 and 8 (20.5%) on exon 8,
      respectively. The concordance rate of immunohistochemistry and PCR-SSCP was 77.9%
      (74/95). The mutation rates of p53 gene in N0, N1, N2 staged lung cancer were
      22.6% (7/31), 44.2% (19/43) and 61.9% (13/21), respectively. The difference was
      statistically significant (P < 0.025). The 3 year survival rate in patients with
      p53 mutations was significantly lower than those without p53 mutations (P <
      0.025). CONCLUSION: The location of p53 mutations in squamous cell carcinoma and
      adenocarcinoma of the lung were more commonly seen on exon 5 and exon 7. p53
      mutations were associated with increased lymph nodes metastasis and reduced
      survival rate in squamous cell carcinoma and adenocarcinoma of the lung.

PMID- 11245001
TI  - [Placental site trophoblastic tumor: a study of clinicopathologic features and
      differential diagnosis].
AB  - OBJECTIVE: To study the clinicopathologic features and differential diagnosis of
      placental site trophoblastic tumor (PSTT). METHODS: 5 PSTT cases were studied and
      compared with 10 choriocarcinoma cases and 2 exaggerated placental site (EPS)
      cases by light and electron microscope examination and immunohistochemical
      staining. RESULTS: PSTT occurs in reproductive women and often following term
      deliveries. Amenorrhea and or vaginal bleeding are common presenting symptoms.
      The serum levels of hCG are often slightly or moderately elevated.
      Microscopically, PSTT is composed of only one kind of trophoblast cell,
      displaying extensive invasion of myometrium and vessels without obvious
      hemorrhage and necrosis. Mitotic figures are not common. Ultrastructure shows
      that the tumor cells contain prominent paranuclear filaments. Immunohistochemical
      reaction reveals positive staining for hPL and mostly negative staining for hCG.
      CONCLUSION: PSTT is a rare trophoblastic tumor with unique microscopic,
      ultrastructural and immunohistochemical features which can help to differentiate
      them from other trophoblastic diseases.

PMID- 11245002
TI  - [p53 gene mutations in mouse skin tumors induced by DMBA-TPA-MNNG].
AB  - OBJECTIVE: To investigate the relationship between p53 gene mutations and mouse
      skin tumors induced by three-step carcinogenesis. METHODS: The exons 5-8 of p53
      gene were examined in 37 DMBA-TPA-MNNG induced mouse skin tumors [including 6
      mice with papillomas, 15 mice having well differentiated squamous cell carcinomas
      (SCCI) and 16 mice with intermediately differentiated squamous cell carcinomas
      (SCC II)]. RESULTS: No p53 gene mutation was detected in the papilloma group,
      whereas 25.8% (8/31) of the SCC group had p53 gene mutations (4/15 of the SCC I
      mice and 4/16 of the SCC II mice). A total of 9 mutations were found in 8 mice
      with SCC, of which 7 were located in exon 8 and 7 were G-->A transitions.
      CONCLUSION: The p53 gene mutations occurred during the process of malignant
      transformation from papilloma to SCC induced by three step carcinogenesis.

PMID- 11245003
TI  - [Problems worthy of being studied in the pathology of lung cancer].

PMID- 11245004
TI  - [A study on the tumor suppressing effect of a specific point mutant p53 minigene
      in the expression regulated model with a tetracycline-transactivative response
      promoter].
AB  - OBJECTIVE: To establish a tetracycline-regulated expression model and to
      determine and verify whether a specific point mutant type p53 minigene,
      containing an Arg-->Leu substitution at amino acid 172, possesses a suppressing
      effect on human lung cancer. METHODS: The tumor suppressing effects of inducing
      apoptosis and inhibition of the formation of G418 resistant colonies of the
      specific point mutated p53 minigene in a structural expression vector on a human
      cancer cell line PG with preexisting dominant negative p53 were preliminarily
      verified. Then the specific p53 minigene was sub-cloned into a tetracycline
      transactivative controlled expression vector pBPSTR1 by gene recombination
      methods. Through LipofectaMINE, the vector was transfected into PG cells under
      the presence of tetracycline (1.0 mg/ml), and the transfectants were screened in
      the selecting medium containing 1.5 micrograms/ml puromycin, the p53 minigene
      expression and tumor suppressing effects were studied dynamically in
      presence/absence (1.0/0 mg/ml) of tetracycline. RESULTS: The specific mutant p53
      minigenes had a stronger tumor suppressing effect than wild type p53 minigene on
      colony formation and transient expression could induce PG cell apoptosis (P <
      0.05). The tetracycline transactivative p53 minigene-regulated transgene model
      was successfully established. When tetracycline was absent, a large amount of
      apoptosis cells in transgenic passage colonies could be detected. Therefore the
      tumor suppressing effects were further verified. CONCLUSION: The specific point
      mutant p53 minigene may be a good candidate for cancer gene therapy. The
      tetracycline transactivative response promoter was found to be a good regulator
      of down stream gene expression, this may be useful in future gene therapy.

PMID- 11245005
TI  - [The relationship between expression of extracellular matrix and clinical
      pathology of primary lung carcinoma].
AB  - OBJECTIVE: To study the relationship between expression of laminin (LN),
      fibronectin (FN), collagen IV (Col. IV) and clinical pathology of primary lung
      cancer. METHODS: LSAB method was used to detect the expression of LN, FN and Col.
      IV in 184 cases of lung carcinoma. RESULTS: Expression of LN and Col. IV in well
      and moderately differentiated pulmonary squamous cell carcinoma were both higher
      than that in poorly differentiated cases (P < 0.01), and marked difference was
      found between lymph node positive and negative cases (P < 0.05). Obvious
      difference in the expression of LN and Col. IV was found between the patient
      groups with squamous cell carcinoma who died within 1/2 year and those surviving
      more than 5 years (P < 0.01), as was the difference in expression of FN (P <
      0.05). Obvious difference in the expression of FN and Col. IV was found between
      patients groups with adenocarcinoma who died within 1/2 year and those surviving
      more than 5 years (P < 0.05, 0.01). CONCLUSIONS: The expression of LN and Col. IV
      correlated with histological grading and lymph node metastasis of pulmonary
      squamous cell carcinoma; LN, FN, Col. IV can also be regarded as a parameter for
      evaluating prognosis of pulmonary squamous cell carcinoma. The expression of FN
      and Col. IV can be regarded as a parameter for evaluating the prognosis of
      pulmonary adenocarcinoma.

PMID- 11245006
TI  - [Changes of nitric oxide synthase in hypoxic pulmonary hypertension and the
      effect of L-arg and L-NAME on pulmonary circulation].
AB  - OBJECTIVE: To study the role of nitric oxide (NO) in Hypoxic pulmonary
      hypertension (HPH). METHODS: NADPH-d and immunohistochemistry were used to study
      the expression and localization of constructive and inducible nitric oxide
      synthase (cNOS iNOS) in the lungs of normoxia and HPH rats, at the same time, the
      effects of L-arginine (L-arg) and nitro-L-arginine-methyl-ester (L-NAME) on
      normoxic and hypoxic pulmonary circulation were investigated. RESULTS: NADPH-d
      positive expression was detected in the endothelium and smooth muscle cells (SMC)
      of large pulmonary vessels (PV) and in the epithelium and SMC of bronchi in the
      HPH group, but negative in the endothelium and SMC of small PV in normoxia.
      Hypoxia not only inhibited the expression of cNOS in the endothelium and SMC of
      PV and epithelium of bronchi, but also induced the expression of iNOS in the
      endothelium and SMC of PV and SMC of bronchi. Administration of L-NAME in
      normoxia had no effect on pulmonary circulation. The effect of administration of
      L-arg and L-NAME in hypoxia on right ventricular hypertrophy and remodeling of PV
      had no significance, compared with simple hypoxia. CONCLUSION: The inhibition of
      cNOS may contribute to the occurrence of HPH, but induced iNOS may depress the
      development of HPH.

PMID- 11245007
TI  - [Zymographic analysis of MMPs in human carcinoma cell lines with different
      metastasis potential].
AB  - OBJECTIVE: To investigate the correlation between matrix metalloproteinases
      (MMPs) activities and metastatic potential of several groups of human carcinoma
      cells with different metastatic potential. METHODS: Several groups of human
      carcinoma cell lines (human lung carcinoma, human prostatic carcinoma and
      melanoma) with different metastatic potential were selected. By using cell
      culture, collection and concentration of conditioned media and zymographic
      analysis method the difference of MMPs production and activity among those cell
      lines were detected. RESULTS: The MMPs production capabilities of carcinoma cells
      rose following the increase of their invasive and metastatic potentials: that of
      PG is much higher than PAa's, and BE1 is higher also than CL3 and LH7. Advanced
      stage melanoma cell WM983a and WM451 product MMP-9, but primary stage cells
      don't. There are MMP-9 in the conditioned medium of prostatic carcinoma cell PC
      3M, the metastatic clone of PC-3 which don't express MMP-9. CONCLUSION: The
      expression of MMPs especially MMP-9 of carcinoma cells is closely correlated to
      the metastatic and invasive potential.

PMID- 11245008
TI  - [An experimental study on the capability of laminin receptor antibody and protein
      kinase C inhibitor to inhibit tumor metastasis in vivo].
AB  - OBJECTIVE: To study methods for blocking tumor metastasis. METHODS: Endogenous
      laminin (LN), protein kinase C (PKC) inhibitor staurosporine (SP), anti-LN
      receptor (LN-R) were used to act on murine fibrosarcoma cells which were strongly
      positive for endogenous LN and LN-R, then infused into the caudal veins of 77 C57
      mice once, to initiate lung tumor formation. Before infusion, the cells were all
      measured for surface LN-R quantity with flow cytometry. RESULTS: The positive
      rate of LN-R on tumor cell surface in the control group, LN group, SP group, anti
      LN-R group and anti-LN group being 56.5%, 76.3%, 50.2%, 31.9% and 20.6%
      respectively. The average volume of the tumors in the lungs of mice being 76 mm3,
      110 mm3, 14 mm3, 5 mm3 and 20 mm3 respectively. The rate of tumor embolus
      formation in lymphatic and blood vessels being 81%, 94%, 36%, 43% and 68%
      respectively. CONCLUSION: The pathological changes and metastasis in the LN group
      are more svere than that in control group. But all other groups are less severe
      than the control group. The level of LN-R on tumor cell surface is positively
      correlated with tumor volume and rat of tumor embolus formation. The lipositol
      conduction system in tumor cells is also closely related with size of tumor foci
      and rate of tumor embolus formation.

PMID- 11245009
TI  - [Effects of antisense cyclin D1 expressing vector on the cell growth and
      apoptosis of pancreatic carcinoma].
AB  - OBJECTIVE: To observe the effects of antisense (AS) cyclin D1 expressing vector
      on the cell growth and apoptosis of pancreatic carcinoma. METHODS: Examination of
      the amplification and expression of cyclin D1 in 5 human pancreatic carcinoma
      cell lines. Our study found the gene amplification and overexpression of cyclin
      D1 in PC-7 cell line cells. We then constructed the antisense cyclin D1 vector
      and transfected the PC-7 cell line with lipofectin. The resultant transformant
      cell line, PC-7/AS-cyclin D1, showed the expression of exogenous antisense cyclin
      D1 mRNA and down regulation of endogenous cyclin D1 mRNA expression and
      inhibition of its protein synthesis detected by Northern blot and Western blot
      respectively. RESULTS: The transformant cells showed retardation of cell growth
      and partial reversion of the malignant phenotype, including decrease of the rates
      of cell growth, DNA synthesis, cell proliferation and metabolism, and also the
      ability of soft agar colony-formation. The tumorogenesis of the transformant
      cells in nude mice was suppressed. G1 arrest was revealed by flow cytometry.
      Apoptosis was identified by DNA fragmentation and in situ TUNEL detection.
      CONCLUSION: Down scaling of the expression of cyclin D1, which plays an important
      role in the regulation of the cell cycle, can effectively inhibit the
      proliferation of carcinoma cells and increase cell apoptosis.

PMID- 11245010
TI  - [A study on the relationship among activity of PDGFBB autocrine loop, cell
      proliferation and apoptosis in human glioma cells].
AB  - OBJECTIVE: To investigate the relationship between activity of autocrine loop of
      platelet-derived growth factor BB (PDGFBB), cell proliferation and apoptosis in
      gliomas. METHODS: 73 human gliomas with different degrees of malignancy were
      studied using in situ hybridization, in situ cell death detection (TUNEL method)
      and immunohistochemistry. RESULTS: The activity of PDGFBB autocrine loop and cell
      proliferation in gliomas correlated positively with each other and increased with
      the degree of tumor malignancy. Apoptosis decreased with the increase of
      malignancy and correlated negatively with the activity of PDGFBB autocrine loop
      as well as proliferation in glioma cells. CONCLUSION: These results suggest that
      all the above parameters have referential value in the evaluation of biological
      behavior of gliomas. Abnormal increase of activity of PDGFBB autocrine loop in
      glioma cells may be an important factor which stimulates cell proliferation and
      inhibits cell apoptosis and plays an important role in the development and
      progression of gliomas.

PMID- 11245011
TI  - [Microsatellite instability in gastric carcinoma and intestinal metaplasia].
AB  - OBJECTIVE: To investigate the role of microsatellite instability (MSI) in the
      carcinogenesis and development of gastric cancer (GC). METHODS: MSI was examined
      in 50 surgically resected gastric cancer specimens and 15 intestinal metaplasia
      specimens using PCR based methods. RESULTS: MSI was detected in 27/50 of GC and
      3/15 of intestinal metaplasia at one or more loci. MSI was positive in all three
      cases of early GC. The incidence of MSI in well differentiated GC (86.6%) was
      significantly higher than that in poorly differentiated GC (P < 0.05). The
      frequency of MSI in intestinal type of GC (77.8%) was significantly higher than
      that in the diffused type (40%, P < 0.05). No significant correlation was found
      between MSI and age, sex, size, location, lymph node metastasis or clinical stage
      of GC. CONCLUSION: MSI is an early molecular marker in the carcinogenesis of GC
      and may play an important role in the development of GC.

PMID- 11245012
TI  - [The relation between DNA replication error and clinicopathological features of
      colorectal carcinoma].
AB  - OBJECTIVE: To study the relationship between DNA replication error and
      development of colorectal carcinoma (CRC). METHODS: Silver staining PCR-SSCP and
      denatured polyacrylamide gel electrophoresis methods were used to detect
      microsatellites instability (MSI) at 4 loci on chromosome 2, 5, 17 in paraffin
      embedded specimens of 60 CRC and their paired normal tissue. If replication
      errors (RER) were found at 2 or more loci, then a diagnosis of RER+ was made.
      RESULTS: RER+ was observed in 19/60 CRC, among which 7 cases had CRC family
      history. According to Amsterdam criteria, 4 were diagnosed as HNPCC(hereditary
      nonpolyposis colorectal cancer), of which 3 cases were RER+. The ratio of RER+ in
      HNPCC (75%) was significantly higher than that among sporadic CRC (28.5%). Most
      RER+ CRC have features of poorly differentiated adenocarcinoma (P < 0.01),
      tendency for right side involvement of the colon (P < 0.05) and a higher
      proportion with family history (P < 0.05). Rate of Dukes A and B stage higher
      than C and D stage (P < 0.05). CONCLUSION: RER+ is a relatively common molecular
      event in CRC. RER+ CRC and RER- CRC have different clinicopathological features
      and behavior.

PMID- 11245013
TI  - [The effect of tissue inhibitor of metalloproteinase-2 gene (TIMP-2 gene) on
      gastric carcinoma cells in vitro and in vivo].
AB  - OBJECTIVE: To study the effect of TIMP-2 gene on the invasive behavior of gastric
      carcinoma cells and to explore the possibility of blocking tumor metastasis.
      METHODS: TIMP-2 gene was transferred into human gastric cancer cell line SGC-7901
      by lipofection technology. The ability of tumor cell invasion was detected by
      Boyden chamber in vitro and tumor invasion animal model in vivo. Type IV collagen
      and type IV collagenase were detected by immunohistochemical technique. RESULTS:
      The invasive ability of gastric cancer cells SGC-7901 transfected with TIMP-2
      gene was significantly inhibited in vivo and in vitro. The expression of type IV
      collagenase in the untransfected group was higher than in the transfected group.
      CONCLUSIONS: TIMP-2 gene transfection can reduce the ability of gastric cancer
      cell invasion in vitro and in vivo.

PMID- 11245014
TI  - [Expression of p16 gene in malignant lymphoma detected by immunohistochemical and
      in situ hybridization techniques].
AB  - OBJECTIVE: To investigate the expression of p16 gene in non-Hodgkin's lymphoma
      (NHL) and its clinicopathological significance. METHODS: Paraffin embedded
      biopsies from 64 patients with NHL were analysed for p16 gene expression by
      immunohistochemical methods and in situ hybridization technique. RESULTS: Of the
      64 NHL cases, 34(53.1%) were positive for p16 protein, 30(46.9%) lacked p16
      protein, most of the positive signals were seen in the nuclei; 45(70.3%) were p16
      mRNA positive, 19(29.7%) lost p16 mRNA and p16 mRNA was clearly observed in the
      cytoplasm of lymphocytes. p16 expression did not show correlation with such
      factors as sex, age and immunophenotype in NHL, but there was a significant
      difference between the pattern of expression of p16 in well differentiated
      lymphomas and poorly differentiated lymphomas (P < 0.05). Moreover, 42 patients
      were followed postoperatively for over 3 years, both p16 protein and mRNA
      correlated with the prognosis of these patients. CONCLUSION: There was a higher
      incidence of negative expression of p16 mRNA and protein in NHL, which indicates
      that p16 gene inactivation may play an important role in the genesis and
      development of some NHL. The frequency of negative expression of p16 mRNA was
      lower than that of p16 protein suggests that it may be due to post
      transcriptional regulation or the unsteadiness of mRNA or protein expressed. The
      positive expression of both p16 mRNA and p16 protein may be features for
      favorable prognosis in patients with NHL.

PMID- 11245015
TI  - [Telomere, telomerase and cancers].

PMID- 11245016
TI  - Report from the Chinese Bone Marrow Transplant Registry with special regard to
      autologous transplant.
AB  - OBJECTIVE: To study the current status of autotransplantation in the People's
      Republic of China and facilitate national and international exchange of relevant
      experiences. METHODS: On the basis of the materials collected from the member
      units around our country, various statistical methods, such as Kaplan-Meier and
      chi 2 tests, were used to estimate the probabilities of leukemia free survival
      (LFS). RESULTS: Up to July 31, 1996, a total of 1213 cases of stem cell
      transplantation (SCT) were performed in 61 medical units in the People's Republic
      of China, and 22 of the units are able to perform both allogeneic SCT (Allo-SCT)
      and autologous-SCT (ASCT). The remaining 41 units had the capacity only to
      perform autologous-SCT. There were 772 cases of autologous SCT performed. The
      three year probabilities of leukemia free survival for acute mylogeneous leukemia
      complete remission (AML-CR1) and acute lymphocyte leukemia complete remission
      (ALL-CR1) recipients were 56% and 42.8%, respectively. The three year
      probabilities of relapse were 44.8% and 47%, respectively. Among the patients
      with acute leukemia who attained CR1 within 40 days of diagnosis and who
      subsequently underwent autotransplantation within three to six months, the three
      year probabilities of LFS for acute mylogenous leukemia (AML) and acute
      lymphocyte leukemia (ALL) were 72% and 50%, respectively. CONCLUSIONS: Patients
      who attained complete remission (CR1) within 40 days after diagnosis and
      underwent subsequent autologous-SCT within three to six months of CR1 enjoyed a
      significantly increased LFS.

PMID- 11245017
TI  - Herbimycin A enhances apoptotic effect of chemotherapeutic drugs on K562 cells.
AB  - OBJECTIVES: To explore the anti-apoptotic mechanism and the effective apoptosis
      inducing method in chronic myelogenous leukemia (CML) cells. METHODS: K562 cell
      line was used to observe the effect of combination of herbimycin A (HMA), a
      tyrosine kinase inhibitor, and chemotherapeutic agents on the induction of
      apoptosis. RESULTS: HMA or chemotherapeutic agents could inhibit the
      proliferation but not significantly induce apoptosis of K562 cells. However, HMA
      significantly enhanced apoptosis when combined with chemotherapeutic agents.
      Addition of sulfhydryl compound to the cultures to conjugate HMA completely
      abrogated this enhancing effect on K562 cells. CONCLUSIONS: HMA increases the
      sensitivity of CML cells to chemotherapeutic agents by inactivating tyrosine
      kinase activity. It is promising that combination of HMA with conventional
      chemotherapeutic drugs may be a new strategy in the treatment of CML.

PMID- 11245019
TI  - Sma I, Hha I, Msp I and Rsa I restriction fragment length polymorphisms in the
      von Willebrand factor gene of Chinese population.
AB  - OBJECTIVE: To study Sma I, Hha I, Msp I and Rsa I restriction fragment length
      polymorphisms in vWF gene of Chinese population. METHODS: The vWF gene from 52
      unrelated individuals of Han Nationality, 44 of Yi tribe, 42 of Dai tribe was
      analyzed by polymerase chain reaction and digestion of the endonucleases of Sma
      I, Hha I, Msp I and Rsa I. RESULTS: The allele frequencies were 0.38:0.62 for Sma
      I+:Sma I- and 0.38:0.62 for Hha I+:Hha I-; 0.20:0.80 for Msp I+:Msp I-; 0.93:0.07
      for Rsa I+:Rsa I- in Chinese Han population. The theoretical heterozygous rates
      were 0.46, 0.46, 0.36 and 0.13 of these polymorphisms, respectively. The allele
      frequencies were 0.43:0.57 for Sma I+:Sma I- and 0.43:0.57 for Hha I+:Hha I-,
      0.26:0.74 for Msp I+:Msp- in Yi tribe and 0.36:0.64 for Sma I+:Sma I- and Hha
      I+:Hha I-, 0.17:0.83 for Msp I+:Msp I- in Dai tribe. The theoretical rates were
      0.49 for Sma I and Hha I and 0.38 for Msp I in Yi tribe; and 0.45 for Sma I and
      Hha I, 0.28 for Msp I in Dai tribe, respectively. CONCLUSIONS: The allele
      frequencies and theoretical rates of these polymorphisms in vWF gene are
      different between Chinese populations and Caucasians. They should be useful for
      the carrier detection and prenatal diagnosis in vWD families of Chinese.

PMID- 11245018
TI  - Bcl-2 gene and its family genes Bax, Bcl-Xl as well as Fas/Apo-1 and their
      clinical significance in acute leukemia.
AB  - OBJECTIVE: To study the suppressing genes of apoptosis, namely Bcl-2, its family
      genes Bax, Bcl-Xl, and the inducing gene of apoptosis Fas/Apo-1. METHODS: The
      techniques of cytoimmuno-histiochemical stains, Western blotting and Northern
      blotting were used. RESULTS: It was found that the antigens of Bcl-2 in acute
      myelogenous leukemia (AML) and acute lymphocytic (ALL) was higher than that in
      the normal (P < 0.01). At same time, Bcl-2 was obviously lower expression in
      complete remission (CR) group than that in non-remission (NR) one by
      retrospective analysis (P < 0.01). Though Bcl-2 was low expression in CR with
      Western blotting, there was no statistical significance (P > 0.05). In CR group
      the expression of Bcl-2 mRNA was obviously lower than that of NR one (P < 0.01).
      Even though leukemia expression of Bax with cytoimmuno-histiochemical stain was
      also lower than that in the normal people, there was no difference between CR and
      NR with cytoimmuno-histiochemical, Western blotting and Northern blotting (P >
      0.05). There was difference of Bcl-Xl mRNA in two groups (P < 0.01). The
      expression Fas/Apo-1 in leukemia was lower than that in normal people (P < 0.01).
      But in CR and NR, there was no difference with cytoimmuno-histiochemical stain
      and Western blotting. CONCLUSIONS: The Changes of genes and their proteins are
      significant theoretically and clinically. The antigen expression of Bcl-2 and the
      expression of Bcl-2 mRNA may be considered as a prognostic index for AML.

PMID- 11245020
TI  - Semi-quantitative study of calcitonin gene methylation in myelodysplastic
      syndrome.
AB  - OBJECTIVE: To evaluate whether hypermethylation of calcitonin (CT) gene could
      serve as a transforming signal of myelodysplastic syndrome (MDS) to leukemia.
      METHODS: Bone marrow aspirates from 35 MDS patients, including 25 refractory
      anemia (RA), 10 refractory anemia with excess of blasts (RAEB) or refractory
      anemia with excess of blasts in transformation (RAEBt) and 7 cases of acute
      myeloid leukemia (AML) transformed from MDS, were studied on methylation rate in
      5' end of CT gene by polymerase chain reaction (PCR) technique using methylation
      sensitive endonuclease Hpa II with external references of undigested DNA and Msp
      I digested DNA and internal reference of 112 bp fragment containing codon 61 of N
      ras oncogene. The results were expressed as calcitonin gene methylation rate
      (CTMR) calculated from the densitometer-analyzed integral calculus of PCR
      products of 566 bp CT(a1), 112 bp N-ras(b1) by using Hpa II-digested DNA and PCR
      products of 566 bp CT (a0), 112 bp N-ras(b0) by using undigested DNA according to
      the formula, CTMR = (a1/b1)/(a0/b0) x 100%. RESULTS: The CTMRs in total 35 MDS,
      25 RA, 10 RAEBt and 7 cases of AML transformed from MDS were 36.87% +/- 25.10%,
      28.12% +/- 24.01%, 58.74% +/- 16.49%, and 54.03% +/- 7.06% respectively,
      significantly higher than that in control group (P < 0.001, P < 0.05, P < 0.001
      and P < 0.001, respectively). CONCLUSION: The results suggest that
      hypermethylation of CT gene occurs in early stage of leukemic transformation and
      CTMR might be a useful marker in predicting the transformation of MDS to AML.

PMID- 11245021
TI  - Contribution of the absence of aspartic acid at position 57 of the HLA-DQ beta
      chain to predisposition to insulin-dependent diabetes mellitus in a southern
      Chinese population.
AB  - OBJECTIVE: To investigate the association of the absence or presence of aspartic
      acid at position 57 of the HLA-DQ beta chain (NA or A) with susceptibility or
      resistance to insulin-dependent diabetes mellitus (IDDM) in a Southern Chinese
      population. METHODS: Sixty-nine IDDM patients and 47 healthy controls in a
      Southern Chinese population were HLA-DQB1 genotyped by one-step sequence specific
      polymerase chain reaction (ssPCR). RESULTS: The frequencies of NA and A were
      64.5% and 35.5% in the IDDM patients, and 40.4% and 59.6% in the control subjects
      respectively (RR for NA was 2.68, P < 0.01). The frequencies of NA/NA, NA/A and
      A/A phenotypes were 47.8%, 33.3% and 18.8% in the IDDM patients, and 31.9%, 17.0%
      and 51.1% in the controls respectively (P < 0.01). The frequency of A/A phenotype
      was significantly lower in the IDDM patients than in the control subjects (RR =
      0.22, P < 0.01). DQB1* 0302 and DQB1* 0201 were more frequent in IDDM patients
      than in control subjects. The younger the age of IDDM onset, the higher the
      allele frequencies of DQB1* 0201 and DQB1* 0302. CONCLUSION: The present study
      suggests that the NA confers the susceptibility to IDDM, while the A confers the
      protection against IDDM in patients of Southern Chinese origin. These
      associations are more clearcut in childhood-onset IDDM patients.

PMID- 11245022
TI  - Gene expression of receptor for advanced glycosylation end products and its
      modulation by aminoguanidine in diabetic kidney tissue.
AB  - OBJECTIVE: To explore the relationship between receptor for advanced
      glycosylation end products (RAGE) gene expression in the kidneys of diabetic rats
      and the role of aminoguanidine on it. METHODS: Among four groups of rats, 2
      groups received streptozotocin (STZ) to induce diabetics (DM) and were followed
      by either aminoguanidine (AG) treatment for 12 weeks or no therapy. Two groups of
      normal rats in which one received AG and the other given water served as control
      (Con). Reverse transcription-polymerase chain reaction (RT-PCR) was used to
      measure the amount of receptor of advanced glycosylation and products (RAGE)
      messenger RNA (mRNA) expression. RESULTS: After 4 weeks of diabetes inducement,
      RAGE mRNA levels showed a continuous increase up to 12 weeks both in diabetic
      renal cortex and medulla compared with mRNA levels at the end of 2 weeks. The
      RAGE mRNA levels in renal cortex and medulla of control rats did not change
      significantly with age. AG as the prototype inhibitor of advanced glycosylation
      end products (AGEs) formation, when administered to diabetic rats for 4 weeks,
      had no visible effect on the alterations of renal RAGE mRNA in diabetes. By
      continuous administration up to 8 weeks, those alterations of RAGE mRNA both in
      diabetic renal cortex and medulla were all ameliorated [P < 0.05, (diabetes
      without AG) versus (diabetes with AG)]. In addition, diabetic animals had a
      progressive increase in urinary protein excretion compared to control rats from
      week 4 onwards. Similarly, after 8 weeks diabetic rats had significantly higher
      glycated Hb (GHb) (DM without AG vs Con: 7.71 +/- 0.22% vs 2.95 +/- 0.52% P <
      0.001). AG treatment for 8 weeks decreased GHb by 24.78% and retarded the rate of
      rise in albuminuria in diabetic rats as compared with that in untreated diabetic
      rats (DM with AG vs DM without AG: 22.04 +/- 0.91 micrograms/24 h vs 70.25 +/-
      13.05 micrograms/24 h, P < 0.001). CONCLUSIONS: Gene expression of RAGE in renal
      cortex and medulla was altered in diabetic rats and excessive gene expression of
      RAGE in kidney tissue may enhance the interactions between advanced glycosylation
      end products (AGEs) and its receptor (RAGE) which would contribute to the
      development of diabetic nephropathy. Cumulative AGEs play an important role in
      increasing RAGE gene expression in vivo. The decrease of AGEs level by AG therapy
      ameliorate the abnormal regulation of RAGE gene expression.

PMID- 11245023
TI  - Supraglottic carcinoma: does preoperative radiotherapy reduce the incidence of
      cervical metastasis?
AB  - OBJECTIVE: To compare surgery (S) alone with combined radiotherapy and surgery (R
      + S) in the management of patients with supraglottic laryngeal cancer. METHODS:
      Between 1981 and 1994, patients were stratified according to stage and randomised
      to either surgery (S) or 4000cGy of radiotherapy and surgery. There were 102
      patients in the S group and 99 in the R + S group who completed at least 3-year
      follow-up. RESULTS: Using Kaplan-Meier survival method showed no significant
      difference between the two groups. When the patients were grouped according to
      tumour stage, a significant reduction in the regional recurrence was noted in the
      R + S group for stage I-III disease (Cox multivariate analysis, P < 0.02). They
      had an increased relative risk of 1.8 (95% confidence 1.1-2.9) for neck
      recurrence. There was no significant difference in neck recurrence rates in the
      two groups for stage IV disease. When Cox proportional hazard model was used,
      only TNM stage (P < 0.02) and histological nodal status (positive lymph nodes, P
      < 0.01) were found to be independent risk factors for regional control.
      CONCLUSION: Preoperative radiotherapy can improve regional cervical control of
      stage I-III supraglottic cancer as compared with surgery alone.

PMID- 11245024
TI  - The protective effect of procaine blocking on nerve-electrophysiological study
      during operation.
AB  - OBJECTIVE: To clinically evaluate the protective effect of procaine blocking on
      nerves. METHODS: Electrophysiological examination before and after procaine
      blocking was conducted on 32 nerves during operation, 18 of which were donor
      nerves and 14 were injured ones. RESULTS: The latency of somatosensory evoked
      potentials (SEPs) was lengthened (15.30%) and the amplitude was lowered (18.47)
      after procaine blocking. Compared with the values before procaine blocking, the
      differences were significant (P < 0.01 and P < 0.05, respectively). SEP waves
      disappeared after procaine blocking in some cases (28.13%). CONCLUSION: Latency
      of SEP is lengthened and amplitude is lowered after procaine blocking. In some
      cases, SEPs even disappear.

PMID- 11245025
TI  - The effect of dimethyl sulfoxide on activation of the major immediate early
      promoter of human cytomegalovirus.
AB  - OBJECTIVE: To evaluate the effect of dimethyl sulfoxide (DMSO) on the major
      immediate early promoter of human cytomegalovirus. METHODS: THP-1 cells were
      transfected with plasmids pCAT760, pIE1-163, pIE1-183, pIE1-193 and pIE1-213,
      respectively, and exposed to dimethyl sulfoxide in the presence or absence of
      lipopolysaccharide. The extracts of these cells were performed by chloramphenicol
      acetyl transferase assay. The nuclear extracts of THP-1 cells treated with
      dimethyl sulfoxide in the presence or absence of lipopolysaccharide were prepared
      for the DNA binding reaction by electrophoretic mobility shift assay. RESULTS:
      Dimethyl sulfoxide increases the expression of the cytomegalovirus major
      immediate early promoter, and also upregulated expression of the minimal major
      immediate early promoter containing triplicates of either the 18 base pair or 19
      base pair sequences. Furthermore, gel mobility shift assays showed that dimethyl
      sulfoxide enhances Nuclear Factor kappa B and CyclicAMP response element binding
      protein to bind to the 18 base pair and 19 base pair repeats. CONCLUSIONS: One
      mechanism whereby DMSO enhances human cytomegalovirus replication is through
      upregulating the major immediate early promoter. This effect on human
      cytomegalovirus gene expression is, in part, related to enhanced Nuclear Factor
      kappa B and CyclicAMP response element binding protein activity.

PMID- 11245026
TI  - Preparation and characterization of monoclonal antibody against recombinant human
      tissue factor pathway inhibitor.
AB  - OBJECTIVE: To prepare and identify monoclonal antibody (McAb) against recombinant
      human tissue factor pathway inhibitor (rhTFPI) and to use it for measurement of
      TFPI by ELISA, and to evaluate the effects of the McAb on dilute prothrombin time
      (PT) and activated partial thromboplastin time (APTT). METHODS: After
      intrasplenic immunization of Balb/c mouse with TFPI, hybridoma technique was used
      to raise monoclonal antibody against rhTFPI. The McAb was well-characterized and
      labelled with horseradish peroxidase (HRP) by using assay of TFPI in ELISA.
      Furthermore, the McAb was added to normal and factor IX deficient plasma for
      observation of dilute PT and APTT. RESULTS: Two hybridomas (4F4, 4F8) secreting
      McAb against TFPI were established. The Ig class and subclass of the McAb
      purified from 4F8 was IgG1. Immunoblotting results indicated that the McAb4F8
      only recognized a single band of TFPI with molecular weight of 34.8 KD. The
      results of Sandwich enzyme-linked immunosorbent assay (ELISA) by using the HRP
      labelled McAb4F8 showed that the mean of TFPI in normal human plasma is 103.2 +/-
      11.5 micrograms/L. The McAb 4F8 was also proved to shorten markedly dilute
      prothrombin time of factor IX deficient plasma and normal plasma. CONCLUSIONS: We
      established two hybridomas cell lines (4F4, 4F8) and obtained the McAb4F8 against
      TFPI and reported the levels of TFPI in healthy adult human plasma by Sandwich
      ELISA with HRP labelled McAb4F8 in Chinese.

PMID- 11245027
TI  - Short-term effects of chemotherapy-surgery-chemotherapy regimen on clinically
      inoperable advanced ovarian cancer.
AB  - OBJECTIVE: To investigate the short-term effects of chemotherapy-surgery
      chemotherapy regimen on clinically inoperable advanced ovarian cancer. METHODS:
      Retrospective analysis was made on 16 cases of stage III and 2 cases of stage IV
      epithelial ovarian cancer with fixed pelvic mass. Neoadjuvant chemotherapy with
      CP (cisplatin + cyclophosphamide) or CAP (CP + adriamycin) regimen was given by
      intraarterial, intraperitoneal, or systemic routes accordingly for an average of
      2.8 courses. Sixteen of the 18 cases were assessed to be operable after
      preoperative chemotherapy. The uterus, adnexa, omentum, pelvic lymph nodes
      (14/18), and implants were included in the cytoreductive surgery. Pelvic masses
      were found to have almost disappeared in 9, and macroscopic residuals were found
      in 11 (residuals < 2 cm in 2, and > 2 cm in 5) of the 18 cases. Postoperative
      chemotherapy (CP, CAP, or CEP, E = VP16) was given for an average of 5.9 courses.
      RESULTS: Five out of 7 patients followed up for over 3 years have been surviving
      for 46, 44, 40, 38 and 36 months, respectively. CONCLUSION: Chemotherapy-surgery
      chemotherapy regimen has beneficial effects on clinically inoperable advanced
      ovarian carcinoma.

PMID- 11245028
TI  - Maternal-fetal transmission of human papillomavirus.
AB  - OBJECTIVE: To investigate the maternal-fetal transmission of human papillomavirus
      (HPV). METHODS: Samples of exfoliated cervical cells were obtained from 73
      pregnant women on their third-trimester examinations. Samples of fetal membranes,
      amniotic fluid and nasopharyngeal swab were obtained from the parturients and
      their neonates. The presence of HPV types 16, 18 and 35 deoxyribonucleic acid was
      detected by polymerase chain reaction (PCR) and endonuclease method. RESULTS: HPV
      types 16, 18 and 35 deoxyribonucleic acid were found in 26 (35.6%) of 73
      specimens of cervical cells obtained from the parturients, and in 31 (42.5%) of
      73 specimens of fetal membranes, 6 (15.4%) of 39 specimens of amniotic fluid, and
      5 (14.7%) of 34 neonatal nasopharyngeal swabs obtained from the neonates. The
      restriction endonuclease analysis of the amplified products showed that HPV types
      16, 18 and 35 were positive in 24.7%, 9.6% and 1.4% respectively of parturients,
      and 11.0%, 4.1% and 0 respectively of neonates. The maternal-fetal transmission
      rate of HPV was 50% (7/14) for spontaneous vaginal delivery, and 33.3% (4/12) for
      cesarean section. CONCLUSION: HPV can be transmitted from mothers to their babies
      not only through the placenta during pregnancy, but also through the genital
      tract during delivery.

PMID- 11245030
TI  - The effect of platyspondyly and pubertal growth spurt on the stature of patients
      with beta-thalassaemia major.
AB  - OBJECTIVE: To study the effect of the body proportion and pubertal growth spurt
      on the stature of children with beta-thalassaemia major. METHODS: The height,
      sitting height, upper to lower segment (U:L) ratio and pubertal development were
      determined in 71 Chinese children (38 girls and 33 boys) with beta-thalassaemia.
      The growth patterns of 20 patients with complete growth data between 3 years and
      final height, were analyzed according to whether they underwent a pubertal growth
      spurt or not. RESULTS: 27% of the boys and 32% of the girls had a height below
      the 3rd percentile. About 60% of all the children had a U:L ratio below the 10th
      percentile for age. Abnormal body proportion was found in patients with or
      without growth retardation. 34% of the 41 children over the age of 14 years
      underwent spontaneous puberty. In 28 patients over the age of 16 years, a growth
      spurt was observed in 46% of the children during spontaneous or induced puberty.
      The retrospective analysis showed that the height deviation from the mean in
      adulthood was significantly higher in patients without pubertal growth
      acceleration than in those with a growth spurt (x = -11.8 cm, s = 7.6 cm vs x = 
      4.4 cm, s = 4.4 cm; P = 0.02). CONCLUSIONS: An abnormal U:L ratio was commonly
      observed in patients with beta-thalassaemia major and may be one factor
      contributing to the short stature of these patients. Abnormal puberty was present
      in a significant proportion of children and the lack of a pubertal growth spurt
      was found to be detrimental to adult height.

PMID- 11245029
TI  - Outpatient diagnostic hysteroscopy: analysis of 429 cases.
AB  - OBJECTIVE: To evaluate the diagnostic accuracy of outpatient hysteroscopy.
      METHODS: Outpatient CO2 hysteroscopy using video-camera for monitoring was
      performed on 429 patients from November 1995 to December 1996. The indications
      included post-menopausal bleeding (32.2%), menorrhagia (25.4%), irregular
      bleeding (24.7%), intermenstrual spotting (10.2%) and others (7.5%). RESULTS:
      Hysteroscopy was successfully performed on 420 (97.9%) patients. Although no
      anaesthetics were used, only two (0.47%) patients complained of severe pain
      during the procedure. Twenty-one (4.9%) patients had poor view due to submucosal
      fibroid or bloody view. There were no operative complications. Normal uterine
      cavity was found in 36.8% and atrophic endometrium in 34.7% of patients. The
      pathologies included submucosal fibroid (10.7%), endometrial polyp (5.8%) and
      fibroid polyp (2.8%). Five (1.2%) out of 429 patients were confirmed
      histologically to have endometrial carcinoma. No malignant lesions were missed. A
      total of 372 (86.7%) patients had histological confirmation of hysteroscopic
      findings. In 57 (13.2%) patients, the histological results did not correlate with
      the hysteroscopic findings. CONCLUSIONS: Outpatient hysteroscopy and suction
      curettage is a safe, cost-effective and acceptable procedure.

PMID- 11245031
TI  - Long-term studies on allotransplantation of rabbit retinal pigment epithelial
      cells double-labelled with 5-bromodeoxyuridine and natural pigment.
AB  - OBJECTIVE: To facilitate the identification of transplanted retinal pigment
      epithelial (RPE) cells, we sought to double-label the cells with 5
      bromodeoxyuridine (BrdU) and with natural pigment. The BrdU is not lost during
      cell division but does require immunohistochemical methods for visualization; the
      pigment on the other hand, allows immediate, obvious identification, but is
      gradually lost with cell division. Together they provide a convenient, long-term
      double label. METHODS: Non-confluent RPE cells at the second to the fifth
      passages were labelled with 5-BrdU and pigment. The double-labelled RPE cells
      were transplanted onto Bruch's membrane of 72 eyes of New Zealand albino rabbits.
      The labelled cells were localized by anti-BrdU antibody and the avidin biotin
      alkaline phosphatase complex (ABC-AP) method, and by visible inclusions of
      pigment. RESULTS: The transplanted RPE cells had distinct basal and apical
      morphology, and were in close contact with the photoreceptor outer segments of
      the host. The BrdU label was restricted to the nuclei of the RPE cells, which
      were stained blue. The pigment was located in the cytoplasm of the apical portion
      of these RPE cells. No evidence of severe rejection was seen. CONCLUSIONS: Using
      this double-label method, transplanted RPE cells could be readily and reliably
      identified till one year after transplantation. The transplanted RPE cells
      revealed normal morphology with some function: they had distinct basal and apical
      morphology as seen in close contact with the outer segment of photoreceptor
      cells. The junctional complexes were well formed with neighboring RPE cells. The
      transplanted RPE cells phagocytose shed outer segments of the host. No evidence
      of rejection was observed, suggesting that the subretinal space of the rabbit may
      possess some degree of immunologic privilege. This experiment provides reliable
      evidence for the clinical research of allotransplantation of RPE cells.

PMID- 11245032
TI  - Stroke-prone renovascular hypertensive rats.
AB  - PURPOSE: To summarized the methods for establishment, characteristics of vascular
      lesions in brain and heart and the application of stroke-prone renovascular
      hypertensive rats (RHRSP). DATA SOURCES AND METHODS: Most published original
      articles about RHRSP in our laboratory were reviewed. RESULTS: After the renal
      arteries were constricted bilaterally with ring-shape silver clips, the stroke
      prone renovascular hypertensive rats were established. Hypertension was produced
      in all RHRSP (100%). The peak of blood pressure in RHRSP reached 29.1 +/- 3.0
      kPa. The lesions of cerebral arteries and arterioles and the damage of cerebral
      capillary structure by hypertension were observed in the RHRSP. The incidence of
      spontaneous stroke was 56.4% within 40 weeks after the renal artery constriction.
      Left ventricular hypertrophy and small coronary arterial lesions in myocardium
      were discovered in all RHRSP. Myocardial infarction occurred spontaneously in
      41.8% of RHRSP. The animal models have been used for the studies on mechanisms of
      stroke and myocardial infarction. CONCLUSIONS: Because the vascular lesions in
      cerebrum and heart in RHRSP are similar to that in human beings with
      hypertension, RHRSP can be used in the studies on mechanisms of hypertensive
      arteriosclerotic stroke and cardiac lesions and on verifying the effects of
      different medications to complications of hypertension, and the results might be
      more reliable than that in animal models without hypertension.

PMID- 11245033
TI  - Telomerase activation in human cancers.
AB  - OBJECTIVE: To review the background of telomerase activation and the methodology
      involved in its determination, and the clinico-pathological significance of
      telomerase activation in human cancers. DATA SOURCES: An English-language
      literature search using MEDLINE (1966-1997) and bibliographic reviews of
      textbooks and review articles. RESULTS: Progressive shortening of telomeres was
      associated with continuous cell division in normal somatic cells. Telomerase was
      activated in most cancer cells and immortal germ cells to maintain their
      telomeric lengths. The occurrence and clinical pathological significance of
      telomerase activation was evaluated in various types of human cancer.
      CONCLUSIONS: Telomerase activation is a common event in human cancers and may be
      as a useful marker for malignant cells. Telomerase may also be a therapeutic
      target for cancer treatment.

PMID- 11245034
TI  - Opening blood-brain-barrier by intracarotid infusion of papaverine in treatment
      of malignant cerebral glioma.
AB  - OBJECTIVE: To find an effective method for the treatment of malignant cerebral
      glioma by opening the blood-brain-barrier (BBB). METHODS: The concentration of
      methotrexate (MTX) in tumor was measured in 18 patients with cerebral glioma, and
      155 patients with malignant glioma were treated by intracarotid infusion of
      papaverine and Bis-chloronitrosourea (BCNU). RESULTS: After intracarotid infusion
      of papaverine for reversible opening of BBB, the MTX concentration in tumor
      tissue was 1810 +/- 380 ng/g, higher than that in patients without papaverine
      infusion (997 +/- 126 ng/g). Eighty-nine patients with glioblastoma and 66
      patients with anaplastic astrocytoma received intracarotid infusion of papaverine
      and BCNU (250 mg) for an average of 2.14 times. The mean survival time of these
      patients was 114.5 weeks, median survival time was 140 weeks, and five-year
      survival rate was 22.97%. CONCLUSION: The combined chemotherapy with papaverine
      and BCNU through intra-arterial infusion is simple, safe and effective in
      treating malignant cerebral glioma so long as the tumor is sensitive to the
      drugs.

PMID- 11245035
TI  - Priority for public health in the People's Republic of China.

PMID- 11245036
TI  - Coexistence of Creutzfeldt-Jakob disease and Alzheimer's disease in the same
      patient.

PMID- 11245037
TI  - High dose progesterone therapy in lymphangioleiomyomatosis: a case report and
      review of literature.

PMID- 11245038
TI  - Angiotropic T cell lymphoma.

PMID- 11245039
TI  - Successive continuous hemodiafiltrations for severe acute pancreatitis in a
      patient with chronic renal failure.

PMID- 11245040
TI  - Fighting off the challenge from interventional medicine.

PMID- 11245041
TI  - Prevention of maternal-fetal blood group incompatibility with traditional Chinese
      herbal medicine.
AB  - OBJECTIVE: To evaluate the effect of traditional Chinese herbal medicine on the
      prevention of hemolytic disease caused by maternal-fetal blood group
      incompatibility. METHODS: A total of 126 Chinese patients with maternal-fetal
      blood group incompatibility were studied, including 105 cases of ABO type and 21
      cases of Rh type incompatibility. The traditional Chinese herbal medicine was
      used for preventative treatment in 79 cases, and 47 cases served as controls. The
      prescription consisted of Herba leonuri 500 g, white peony root 180 g, Banksia
      rose 12 g, root of Chinese angelica 150 g and Rhizomal ligustica 150 g. RESULTS:
      Preventative treatment with traditional Chinese herbal medicine significantly
      reduced the perinatal mortality rate in cases of Rh type incompatibility, from
      50.0% in the control group to 7.7% in the treatment group (P < 0.05). There was
      no death in the cases of ABO incompatibility. The traditional Chinese herbal
      medicine also decreased the degree of hemolysis. The percentage of severe cases
      in the control group was 29.8%, while it was 15.2% in the treatment group (P =
      0.05). The duration of treatment was closely related to the outcomes. In patients
      who used traditional Chinese herbal medicine for more than 10 weeks, the
      incidence of severe hemolysis was 8.2%, compared with 38.9% in those treated for
      less than 10 weeks (P < 0.05). The change of serum immune antibody (A and/or B)
      titers during the treatment was a very important predictive factor for the
      outcome of the pregnancy. CONCLUSION: Traditional Chinese herbal medicine is
      effective not only for ABO type but also for Rh type maternal-fetal blood group
      incompatibility, with no side effects.

PMID- 11245042
TI  - Three-dimensional reconstruction of electron beam computed tomography angiography
      for evaluating coronary artery bypass grafts.
AB  - OBJECTIVES: To probe into electron beam computed tomography (EBCT) angiography
      and 3-D reconstruction of coronary artery bypass grafts (CABG) and to evaluate
      the clinical application of EBCT angiography and 3-D reconstruction of CABG.
      METHODS: EBCT angiography with 3-D reconstruction was achieved in 150 patients
      (142 men and 8 women, mean age, 57 +/- 8 years) with 399 grafts including 100
      internal mammary artery grafts (IMG), 296 saphenous vein grafts(SVG) and 3 radial
      artery grafts (RAG) respectively. The time from bypass surgery to EBCT scanning
      ranged from 7 days to 120 months, averaging 15 +/- 28 months. Enhanced single
      slice mode (SSM) and flow studies were performed in all patients. The results of
      3-D reconstruction of CABG were compared with bypass operation records and with
      coronary arteriograms (7 patients). RESULTS: 150 patients underwent successfully
      EBCT angiography and CABG 3-D reconstruction. According to 3-D reconstruction of
      the coronary bypass grafts with flow studies, 318 of 399 coronary bypass grafts
      were patent including IMG patency in 87/100 (87%), SVG in 228/296 (77%) and RAG
      in 3/3 (100/100). The overall patent rate was 79.7%. In 7 patients with 12
      coronary bypass grafts, EBCT studies showed graft patency (7 grafts) and
      occlusion (5), which were confirmed by conventional graft angiography.
      CONCLUSIONS: EBCT angiography with 3-D reconstruction is effective in providing
      the entire anatomic structure of coronary bypass grafts and evaluating coronary
      bypass graft patency. EBCT flow study can provide quantitative data for
      evaluating coronary bypass graft patency and for supplemental diagnosis of CABG 3
      D reconstruction. EBCT angiography is a noninvasive technique that could replace
      conventional coronary arteriography for follow-up survey of coronary bypass
      surgery in future.

PMID- 11245043
TI  - Nasopharyngeal carcinoma: dynamic MR imaging with gadolinium.
AB  - OBJECTIVE: To evaluate the use of enhanced dynamic MR images in nasopharyngeal
      carcinoma (NPC). METHODS: Dynamic enhanced turbo spin-echo transverse images were
      obtained in 35 patients with newly diagnosed NPC. Comparison was made between the
      pre-contrast image, last enhanced scan and dynamic series in assessment of the
      extent of primary tumor and lymph node involvement. RESULTS: Enhanced MR images
      improved delineation of tumor in the following regions, nasopharyngeal wall
      (6/35), levator palatini (44/70), tensor palatini (12/70), prevertebral muscles
      (3/70), medial pterygoid muscle (7/70), pharyngobasilar fascia (30/35),
      parapharyngeal fat space (23/70), nasal cavity (33/70), oropharynx (6/35),
      sphenoid sinus (6/35), maxillary sinus (6/70), ethmoid air cells (14/35),
      cavernous sinus (5/35), cranial fossa (4/35), clivus (13/35) and pterygoid genu
      (2/70). Eight of the 9 normal and 79/82 abnormal nodal groups, on conventional
      imaging criteria, enhanced with the same pattern and intensity as the primary
      tumor. The dynamic series did not improve delineation of tumor extent in
      comparison with that obtained on last enhanced image. CONCLUSION: Enhanced MR
      images are valuable in evaluating the extent of primary tumor. Dynamic imaging
      was of no additional benefit in the evaluation tumor extent.

PMID- 11245044
TI  - Avascular necrosis of the femoral head: MR imaging with radiological and
      histological correlation.
AB  - OBJECTIVE: To assess the value of MR in the diagnosis of avascular necrosis (AVN)
      of the femoral head. METHODS: MR images in 34 consecutive patients (26 men and 8
      women) with AVN (57 hips) were reviewed. All lesions were confirmed by
      radiographic, radionuclide, computed tomographic, and/or histologic examination.
      Eleven specimens were obtained after total replacement of the hip. Four hips
      underwent biopsy. All MR images were obtained using a 0.35 T superconductive
      imaging unit with SE sequence. Specimens were cut coronally into 5 mm thick
      section and radiographs were obtained. RESULTS: There were four types of MR
      patterns of AVN. Type one appeared liner or patchy low signal area in the
      superoanterior portion of the femoral head. In type two, a band or ring of low
      signal intensity was found surrounding a central area of high signal intensity on
      T1WI and intermediate signal intensity on T2WI. The low signal band or ring
      consisted of thickened trabecular bone, mesenchymal and fibrous tissue, and
      amorphous acidophilic cellular debris. The central zones within the ring were
      composed of necrotic bone and marrow that had not been reached by the repair
      process. In type three, the focal subchondral region showed intermediate signal
      intensity on T1WI and high signal on T2WI surrounded by a low signal ring. The
      low signal ring consisted of thickened trabecular bone and little mesenchymal
      tissue. The central area was composed of mesenchymal tissue rich in capillaries
      and cystic necrotic zones. In type four, the signal intensity of femoral head was
      inhomogeneous on both T1WI and T2WI. There were low signal bands in the femoral
      neck surrounding the necrotic zone. Only limited areas of some lesions had signal
      intensity isointense with fat on T1WI and T2WI. The inhomogeneous area of low
      signal intensity consisted of a mixture of necrotic bone and marrow, amorphous
      cellular debris. The first type of MR pattern corresponded to the early stage of
      radiograph, and the third type of MR pattern to stage 5. The second and fourth
      type of MR patterns correlated less with the radiographic stage. CONCLUSIONS: MR
      imaging plays an important role in the diagnosis of AVN of femoral head
      especially in the early detection of AVN. The MR patterns of AVN is not
      correlated with radiographic stages exactly.

PMID- 11245045
TI  - Expression of splice variants of CD44 mRNA and its significance in human primary
      hepatocellular carcinoma.
AB  - OBJECTIVE: To investigate the relationship between the expression of splice
      variants of CD44 (CD44v) and the metastasis of primary hepatocellular carcinoma
      (PHCC) in humans. METHODS: The expression of metastasis-associated CD44v mRNA in
      54 specimens of human PHCC was detected by reverse transcription and polymerase
      chain reaction (RT-PCR) method. RESULTS: CD44v mRNA was expressed in 50 (92.59%)
      of the 54 specimens of PHCC, with moderate or over expression in 42 (77.78%).
      Among the 42 specimens with moderate or over expression, deficient tumor capsules
      were found in 25 (59.52%), penetration of tumor capsule in 15 (35.71%), tumor
      emboli in the portal vein in 34 (80.95%), and daughter tumor nodules in 29
      (69.05%). Meanwhile, 12 of the 54 specimens showed negative or weak expression of
      CD44v mRNA. Of them, all had tumor capsules, 1 (8.33%) had penetrated tumor
      capsule, 1 (8.33%) had tumor emboli in the portal vein, and 2 (16.67%) had
      daughter tumor nodules. CONCLUSION: CD44v may contribute to the metastatic
      potential of PHCC.

PMID- 11245046
TI  - Glycophorin variants and contents of sialic acid and total sulfhydryl groups on
      erythrocyte membranes of residents in a malaria hyperendemic area.
AB  - OBJECTIVE: To conduct a screening survey of glycophorin (GP) variants and observe
      the content changes of sialic acid (SA) and total sulfhydryl (SH) groups on the
      erythrocyte membranes among residents in a tertian malaria hyperendemic area of
      Guizhou Province. METHODS: GP variants were detected in the erythrocyte
      hemolysates of 173 local residents at two villages of Libo County by SDS-PAGE on
      10% to 15% gradients gel and Western immunoblotting. Their SA and total SH group
      contents were estimated in erythrocyte membranes by spectrophotometric methods.
      114 healthy subjects in Changsha and 49 individuals at a neighbouring village of
      the above area showing low morbidity of malaria served as normal and endemic
      controls respectively. RESULTS: Three distinct types of GP variants were found
      among 19 propositi in this hyperendemic area. The incidence of GP variants was
      7.9% (8/101) at Yaolu Village whose population was mainly composed of Yao ethnic
      group; while that of Buyi ethnic group at Maolan Village was higher (15.3%;
      11/72). The erythrocyte membrane contents of SA in residents at both villages
      exhibited a very significant tendency of decline (P < 0.01), whereas those of
      total SH groups increased prominently in residents of Yaolu Village only (P <
      0.05). CONCLUSIONS: The frequency of GP variants in this hyperendemic area does
      not depend upon the severity of malarial prevalence. The evident reduction of SA
      contents in the residents may be related to the breaking down of the SA residues
      on membrane GPs by the invasion of Plasmodium vivax.

PMID- 11245047
TI  - Paediatric liver transplantation: Queen Mary Hospital experience.
AB  - OBJECTIVE: To assess the results of paediatric liver transplantation in our
      institution. METHODS: From September 1993 to November 1996, 10 living-related
      liver transplants (LRLT) and 3 reduced-size liver transplants (RSLT) were
      performed on 12 children at our hospital. The medical records of the patients
      were reviewed. All patients suffered from end-stage liver disease resulting from
      biliary atresia with failed Kasai's operations. Their ages at initial
      transplantation ranged from 8 months to 11 years. Excluding the 2 older children
      aged 7.5 and 11 years, the remaining patients were aged 10.5 months on the
      average and weighed 6 to 9.5 kg (mean: 6.8 kg) at the time of initial
      transplantation. RESULTS: All living donors were discharged on postoperative day
      4 to 8 and resumed their previous normal activities. All recipients were alive
      with normal liver function and growing after a follow-up period of 3-40 months
      (mean: 21 months). The patient survival rate was 100%. One patient with RSLT had
      hepatitis of undetermined aetiology and underwent retransplant with a graft from
      her mother. The graft survival rate was 92%. Postoperative complications
      included: postoperative bleeding (n = 3), hepatic vein stenosis (n = I), biliary
      enteric anastomotic stenosis (n = 3), intestinal perforation (n = I) and portal
      vein thrombosis (n = I). They were all treated promptly. In all patients, the
      hepatic artery (diameter ranged from 1.5 to 2.5 mm) anastomosis was achieved by
      microvascular technique. There was no hepatic artery thrombosis in our patients.
      CONCLUSION: With technical refinements, early detection and prompt treatment of
      complications, and advances in immunotherapy, excellent results can be achieved
      in paediatric liver transplantation.

PMID- 11245048
TI  - Experimental study on distribution of serotypes and antimicrobial patterns of
      group B streptococcus strains.
AB  - OBJECTIVE: To obtain information on the distribution of serotypes and
      antimicrobial agent susceptibilities to group B streptococcus (GBS) strains
      isolated in Beijing area from 1991 to 1996. METHODS: Bacterial isolates of GBS
      were obtained from vaginal and cervical tract of pregnant and nonpregnant women
      in Beijing Tian Tan Hospital by culture. A total of 76 GBS strains were
      identified finally by coagglutination. Serotyping was determined by Standard
      Lancefield method. Susceptibility to test agents was assessed by determining the
      minimal inhibitory concentrations (MICs) with agar dilution method that was
      established by the National Committee for Clinical Laboratory Standards (NCCLS).
      RESULTS: Seven serotypes were identified among 76 GBS strains isolates. Types II
      (33%), III (23%) and I a (16%) were the predominant serotypes in pregnant and
      nonpregnant women. MICs of penicillin G and ampicillin were < or = 0.06
      microgram/ml. MICs of cephazolin, cefuroxime and cefoperozone were 0.003
      microgram/ml-0.06 microgram/ml. MICs of erythromycin were 0.003 microgram/ml-0.03
      microgram/ml. MICs of gentamycin were 1 microgram/ml-32 micrograms/ml. MICs of
      amikacin were 4 micrograms/ml- > or = 64 micrograms/ml, nearly 12.8% and 40.4% of
      the strains were resistant to gentamycin and amikacin, respectively. CONCLUSIONS:
      Our study provides useful epidemiologic data for preparation of GBS type-specific
      vaccines which can prevent GBS infections and antimicrobial agents susceptibility
      patterns in China. Routine reports on GBS susceptibilities by clinical
      laboratories and continuous surveillance for changes in the susceptibility are of
      considerable clinical importance.

PMID- 11245049
TI  - Hyperoxia-induced lung injury in premature rat: description of a suitable model
      for the study of lung diseases in newborns.
AB  - OBJECTIVE: To provide suitable animal model (hyperoxia-induced premature rat lung
      damage) for research of bronchopulmonary dysplasia (BPD) and to better understand
      pathogenesis of BPD and look for effective drugs to prevent and treat BPD.
      METHODS: Rat litters delivered prematurely at 21-day gestation by hysterotomy.
      Vigorous resuscitation at birth resulted in a high survival rate. Surfactant and
      antioxidant enzyme (AOE) system were measured. The model was tested in an
      experiment of hyperoxia-induced lung injury. RESULTS: Compared to litters
      delivered spontaneously at term (gestation 22 days), these preterm rats had
      immature pulmonary surfactant composition with low total phospholipid (x +/- s:
      10.09 +/- 1.49 micrograms/mg wet weight vs 12.04 +/- 1.31 micrograms/mg wet
      weight; P = 0.0367) and phostidylcholine (5.06 +/- 1.82 micrograms/mg wet weight
      vs 8.28 +/- 2.35 micrograms/mg wet weight; P = 0.0238) levels. The concentrations
      of AOE enzymes, superoxide dismutase (11.40 +/- 2.04 mu/mg DNA vs 15.78 +/- 1.84
      mu/mg DNA; P < 0.01) and catalase (92.81 +/- 62.25 mu/mg DNA vs 412.24 +/- 117.50
      mu/mg DNA; P < 0.01) were also significantly lower. Animals exposed to hyperoxia
      had a significantly higher mortality. Pulmonary edema and histological features
      of lung damage were observed in the pups exposed to hyperoxia. CONCLUSIONS: The
      premature rat model is relatively cheap, readily available and has a high
      survival rate. Pulmonary surfactant and AOE systems are immature. These
      properties make them a suitable model for the study of acute and chronic lung
      damage related to prematurity and O2 toxicity.

PMID- 11245050
TI  - Protective effect of recombinant human augmenter of liver regeneration on CCl4
      induced hepatitis in mice.
AB  - OBJECTIVE: To observe the anti-injury role of recombinant human augmenter of
      liver regeneration. METHODS: To establish liver injury models induced by CCl4 in
      vivo and in vitro, cell survival rates and LDH release rates served as observing
      index in experiments in vitro. Survival rates of liver failure animals, serum
      concentration of ALT, LDH, DNA and pathological examination were selected as
      parameters in experiment in vivo. RESULTS: rhALR could increase the survival
      rates and decrease the LDH release rates of injured hepatocytes in vitro. rhALR
      could also increase the survival rates of liver failure animal, promote
      hepatocyte proliferation and decrease the serum level of ALT and LDH in vivo.
      CONCLUSION: ALR is an important stimulator for liver regeneration and may play
      important role in liver damage repair.

PMID- 11245051
TI  - Clinical study on reservation of part of stomach for patients with cardiac cancer
      of the gastric stump.
AB  - OBJECTIVE: To explore the clinical significance of the resection of the cardia
      and fundus for patients suffering from cardiac cancer of the gastric stump.
      METHODS: Twenty-five patients suffering from cardiac cancer with a mean period of
      13 years and 3 months after subtotal gastrectomy were included in this study.
      Their average age was 59.1 years. Among them, 19 patients got exploratory
      thoracotomy. RESULTS: Of the 19 patients, 1 was inoperable, 1 underwent resection
      of the gastric stump and esophagojejunostomy because of his huge tumor, 17
      underwent resection of the cardia and fundus of the gastric stump and accepted
      gastroesophagostomy (9 were subjected to tunnel gastroesophagostomy and 8 to end
      to-end esophagogastrostomy). The largest tumor was 5 cm x 4 cm in size. Except
      for a death resulting from intestinal obstruction following operation, the others
      attained a good recovery. The longest period of survival was 4.5 years.
      CONCLUSIONS: Resection of the cardia and fundus and gastroesophagostomy can be
      carried out for patients suffering from cardiac cancer of the gastric stump. The
      method is in line with the principle of the conservation surgery.

PMID- 11245052
TI  - Effects of combined radiation and thermal burn injury on the survival of skin
      allograft and immune function in rats.
AB  - OBJECTIVES: To investigate the effects of combined radiation and thermal burn
      injury on the survival of skin allografts and to analyze the relationship between
      the prolongation of allograft survival and the changes of immune functions of the
      thymocytes and splenocytes in rats. METHODS: Wistar rats were irradiated with 3,
      4, 5, 6 and 8 Gy of gamma rays. Thirty minutes after radiation, 15% TBSA III
      degree burn was inflicted to the rats. Twenty-four hours after the burn injury,
      allografts were used to cover the burn wounds. In the 8 Gy group, 1 hour before
      skin grafting, the bone marrow cells (4 x 10(8)) from the same donor were also
      transplanted. All rats were carefully observed after injury. The rats with single
      radiation injury of 5 Gy gamma rays, with single burn injury and with combined
      radiation-burn injury were killed 3, 7, 10, 15 and 30 days after skin grafting
      for immunological assay and pathological study. RESULTS: All the allografts in
      the single burn group were rejected in 10 days. In the combined injury groups,
      the survival rates of the allografts in rats undergoing 3 and 4 Gy radiation were
      20% and 30%, respectively. In the combined injury groups undergoing 5, 6 and 8 Gy
      radiation, the 10-day survival rates of the allografts were 69%, 88% and 100%
      respectively, and the 30-day survival rates in the three groups were 36%, 42% and
      100% separately. The grafted allogenic skin, with normal epithelial cells and
      good vascularity, healed well with the recipient's skin. Hairs grew well from the
      allografts 30 days after grafting. Three, 7 and 15 days after allografting, in
      the single burn group, the proliferative activities of the thymocytes were 90%,
      185% and 130% of the preinjury level, and the antibody forming capacities of the
      splenocytes were 200%, 171% and 300% of the preinjury level, respectively; in the
      combined injury groups, the proliferative activities were 6%, 99% and 91% of the
      preinjury level, and the forming capacities were 2%, 36% and 90% of the preinjury
      level. CONCLUSIONS: The survival rate of allograft in rats undergoing combined
      radiation and thermal burn injury rises with the increase in radiation dosage.
      The allograft covering single bun injury is severely rejected by immune reaction.
      The prolongation of the survival of allograft in combined injury group mainly
      results from radiation that suppresses immune functions.

PMID- 11245053
TI  - Pathological characteristic of Alzheimer's disease produced by lesion in nucleus
      basalis of Meynert in rats.
AB  - OBJECTIVE: To find out if the lesion in nucleus basalis of Meynert (nbM) can
      induce some morphological changes characteristic of Alzheimer's disease. METHODS:
      Kainic acid was injected into nbM of the rats, and the behavioral deficiency and
      the morphological changes in the cortex and hippocampus were observed by
      methenamine silver staining and electron microscopical examination. RESULTS:
      After 9-15 months of breeding following nbM-lesion, we observed many pathological
      changes in this animal model, which were characteristic of Alzheimer's disease in
      human, and especially we could find for the first time the formation of senile
      plagues after 15-month breeding. CONCLUSION: It is proposed that the degeneration
      of nbM neurons might be primary and responsible for the pathological changes in
      other brain tissues in sporadic Alzheimer's disease.

PMID- 11245054
TI  - Mirror writing in the elderly.
AB  - OBJECTIVE: To determine if examination of mirror writing in the elderly could be
      used to assess the degradation of the brain function. METHODS: The occurrence of
      mirror writing in 146 subjects was examined. Among them, 104 were males and 42
      females. All subjects were university graduates. Age ranged from 40 to 85 years
      with an average of 62.7 +/- 13.4. These subjects were divided into two groups, a
      non-elderly group consisting of 60 subjects (41.1%) and an elderly group 86
      subjects (58.9%). All 146 subjects were examined with 10 items for determination
      of handedness, mini-mental state examination and the written language of Chinese
      Aphasia Examination Scale (Draft) including spontaneous writing, writing from
      dictation and copying. The above mentioned performances of written language were
      done by left and right hand. RESULTS: The results of examination revealed that in
      146 subjects there were 7 subjects with mirror writing, which occurred only in
      the elderly group, accounting for 8.1%. In the elderly group, mirror writing was
      found in one subject of 70-79 years group and 6 subjects of age over 80 years.
      Mirror writing appeared in the elderly was of mild degree with an average
      percentage of 1.9 +/- 0.4. CONCLUSION: It is suggested that examination of mirror
      writing in the elderly may be used to assess the degradation of the brain
      function in senile subjects.

PMID- 11245056
TI  - Clinical use of nonthoracotomy cardioversion-defibrillation system.
AB  - OBJECTIVE: To summarize our experience in 22 patients who had attempted
      nonthoracotomy implantable cardioverter-defibrillators (ICD) for malignant
      ventricular arrhythmias (VA). METHODS: Indications for implantation were
      ventricular fibrillation (VF) in 17 patients and refractory ventricular
      tachycardia in 5. Thirteen patients of them had underlying ischaemic heart
      disease. Seven had dilated cardiomyopathy and two had arrhythmogenic right
      ventricular dysplasia. RESULTS: 20 out of 22 patients were successfully implanted
      nonthoracotomic ICD with defibrillating threshold of 16.7 J. The mean hospital
      stay was 7.8 days. The complications included chest wall haematoma and
      ventricular lead dislodgment requiring repositioning. In the follow-up period of
      10.1 +/- 8 months, 6 patients with VA were treated successfully by ICD.
      CONCLUSION: Nonthoracotomy ICD is possible in a vast majority of patients (91%)
      and should be considered in all patients requiring ICD without concomitant
      surgery.

PMID- 11245055
TI  - Histochemical and immunohistochemical studies of distribution of
      acetylcholinesterase-positive fibers and peptidergic terminals in the nasal
      mucosa of rats.
AB  - OBJECTIVE: To further investigate the mechanism of nasal secretion closely
      related to the innervation patterns in nasal mucosa with emphasis on the
      acetylcholinesterase (AChE)-positive fibers and peptidergic terminals in nasal
      mucosa as well as trigeminal ganglion (TG) cells. METHODS: Histochemical
      demonstration of AChE-positive fibers, immunohistochemical study of the
      distribution patterns of multiple peptidergic terminals, double labelling of AChE
      and substance P (SP) and somatostatin (SOM) mRNA in situ hybridization were
      carried out in nasal mucosa and trigeminal ganglion (TG) in rats. RESULTS: AChE
      positive terminals were mainly distributed in the mid to posterior one third of
      septal nasal mucosa, with greater staining density on the walls of small vessels
      and glands. There were fewer such terminals in turbinate mucosa. Tachykinins
      ergic terminals, including substance P (SP)-, neurokinin A (NKA)-, neurokinin B
      (NKB)- and calcitonin gene-related peptide (CGRP)-ergic terminals, had an
      extensive localizations in nasal mucosa, involving the following areas: between
      epithelial cells, submucosa, the walls of small vessels, glands and venous
      sinusoids in both septal and turbinate nasal mucosa. Septal mucosa had the
      greater density. There were overlaps in the distribution of these peptidergic
      terminals. There were also vasoactive intestinal peptide (VIP)-, neuropeptide Y
      (NPY)- and galanin (GAL)-ergic terminals in nasal mucosa. But no neurotensin (NT)
      and somatostatin (SOM)-ergic terminals were found. In situ hybridization
      revealed SOMmRNA expression in TG cells. AChE and nine neuropeptides existed in
      the cytoplasms of TG cells. Besides, AChE and SP could exist simultaneously in
      cytoplasms of TG cells. CONCLUSIONS: AChE-positive (corresponding to
      parasympathetic nerves) and peptidergic terminals have different distribution
      patterns in the nasal mucosa of rats, although an overlap does exist, indicative
      of their different physiological effects on the regulation of nasal secretion and
      other functions; AChE and multiple neuropeptides in the cytoplasm of TG cells
      might play a role in modulating the nasal secretion in response to stimuli in the
      nasal mucosa.

PMID- 11245057
TI  - Effect of crystalloid cardioplegic solution at different calcium concentration on
      immature myocardium.
AB  - OBJECTIVE: To determine the myocardial protective effect of crystalloid
      cardioplegic solution at different calcium concentration on immature myocardium.
      METHODS: Isolated perfused neonatal rabbit hearts from three groups, arrested by
      intermittent infusion of St. Thomas II cardioplegic solution with different
      concentration of calcium (in each group, only calcium concentration of
      cardioplegic solution was modified, I. [Ca2+] 0.6 mmol/L; II. [Ca2+] 1.2 mmol/L;
      III. [Ca2+] 2.4 mmol/L), were kept ischemic globally at 20 degrees C for 90
      minutes and then followed by 30 minutes of reperfusion in Langendorff mode.
      RESULTS: Although the recovery of LVDP, +dp/dtmax at calcium content of 2.4
      mmol/L after 10 minutes of reperfusion was significantly higher than those at 0.6
      and 1.2 mmol/L calcium (P < 0.05, P < 0.01, respectively). The declined tendency
      of left ventricular hemodynamics after 20 minutes of reperfusion in this group
      was detected. By the end of reperfusion, the left ventricular functional recovery
      at 2.4 mmol/L calcium did not differ from those at 1.2 and 0.6 mmol/L calcium.
      Conversely, postischemic left ventricular functions at 0.6 and 1.2 mmol/L calcium
      were gradually improved during 30 minutes of reperfusion. In 2.4 mmol/L calcium
      group, the Ca(2+)-ATPase activity significantly increased (P < 0.01, P < 0.001)
      whereas myocardial ATP content was lower when compared with 1.2 mmol/L (P <
      0.001) and 0.6 mmol/L calcium groups. CONCLUSIONS: Our research demonstrated that
      there were no statistical differences with respect to hemodynamic recovery in
      three groups after 30 minutes of reperfusion although left ventricular functional
      recovery at 2.4 mmol/L calcium accelerated early after reperfusion. In addition,
      with 2.4 mmol/L calcium, myocardial ATP content was decreased significantly. We
      conclude that, from the point of view of myocardial energy metabolism, St. Thomas
      II cardioplegic solution at high concentration of calcium can not provide
      immature myocardium with optimal myocardial protection while with 1.2 mmol/L
      calcium, however, better high-energy store can be preserved.

PMID- 11245058
TI  - Visco-supplementation therapy in internal derangement of temporomandibular joint.
AB  - OBJECTIVE: To study if visco-supplementation therapy is useful to the internal
      derangement (ID) of temporomandibular joint (TMJ). METHODS: Sixty-three ID cases
      (69 TMJs) were studied by visco-supplementation therapy. The upper and/or lower
      articular cavities were irrigated with 5 ml normal saline and injected 0.3-1.0 ml
      1% hyaluronate (HA) into articular cavity. If the symptoms of the disease still
      existed one week later, the therapy should be repeated for 1-2 times, once a
      week. The control group cases were injected 1 ml 2% lidocaine instead of HA. 8
      other TMJs of 6 ID cases and 2 normal cadavers were studied with scanning
      electron microscopy (SEM) and light microscopy (LM). RESULTS: The visco
      supplement therapy was useful to ID patients. The difference between the test
      group and control group had statistical significance (chi 2 = 6.6535, P < 0.01).
      SEM and LM showed that the condyle, disc and bilaminar region in ID were
      degenerated or destroyed. CONCLUSIONS: The friction between the articular
      surfaces in ID was increased and the bilaminar region could not retract the disc
      as in healthy TMJ. The visco-supplementation therapy can decrease the friction
      and resume the normal rheology of the diseased TMJs.

PMID- 11245060
TI  - Concepts and techniques of conscious sedation.

PMID- 11245059
TI  - Lack of evidence of active lytic replication of Epstein-Barr and
      cytomegaloviruses in patients with systemic lupus erythematosus.
AB  - OBJECTIVES: Systemic lupus erythematosus (SLE) is a multifactorial disease.
      Environmental factors such as viral infection(s) have been proposed as
      pathaetiological factors. There are particular interests in studying lymphotropic
      viruses such as the Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Although
      previous case reports and in vitro studies suggested that they may have a role,
      there is no direct evidence that onset of SLE or disease exacerbation is
      associated with active infection by these viruses. Using the very sensitive
      polymerase chain reaction (PCR) technique, we tried to find out evidence of
      active replication of these viruses in patients with SLE. METHODS: Thirty-four
      patients with SLE were compared with matched normal controls. Eleven patients
      were newly diagnosed to have SLE and 18 of the 34 patients had active disease as
      determined by a SLE Disease Activity Index (SLEDAI) score of > or = 10 at the
      time of study. RESULTS: Our results showed no evidence of active replication or
      reactivation of EBV in the leucocytes amongst the newly diagnosed SLE patients,
      established SLE patients, patients with SLEDAI > or = 10, patients with SLEDAI <
      10, and control subjects. There was no evidence of CMV infection in any of the
      subjects studied. The IgG and IgA responses against EBV early antigen (EA) and
      viral capsid antigen (VCA) were also studied. The IgG and IgA responses against
      VCA of EBV were increased in patients with SLE when compared with controls.
      However, there were no differences in these responses among different subgroups
      of patients. The mechanism of these responses was not apparent but may represent
      non-specific hyperimmune responses in these patients. There were no differences
      in the titre of IgG and IgA against EBV EA between the patient groups and
      controls. CONCLUSION: There is no direct evidence that either EBV or CMV plays a
      direct role in the onset and/or exacerbation of SLE.

PMID- 11245061
TI  - Myospasm of internal anal sphincter in children.
AB  - OBJECTIVE: To introduce a common but not well-recognized acute abdominal disease
      in children. METHODS: Thirty-eight children with spasm of the internal anal
      sphincter were reviewed. RESULTS: The main symptom was the sudden onset of
      continuous pain in the lower abdomen with paroxysmal exacerbation. The typical
      sign was the dilation of the sigmoid colon with tenderness aggravated by
      pressure. Plain X-ray films showed dilation of the sigmoid colon and rectum. The
      symptoms could be relieved by digital rectal examination or a glycerin
      suppository. CONCLUSIONS: It is the temporary achalasia of the internal anal
      sphincter that causes acute abdominal pain.

PMID- 11245062
TI  - Suicide effect on rat gliomas mediated by recombinant adenovirus thymidine
      kinase/acyclovir system.
AB  - OBJECTIVE: To establish the replicated-deficient recombinant adenovirus-mediated
      thymidine kinase/acyclovir (Adtk/ACV) system and to evaluate its suicide effect
      on rat C6 brain gliomas in vitro and in vivo. METHODS: The plasmid pAdtk and
      pJM17 were co-infected into 293 cells (adenovector packaging cells) and the
      results were identified by polymerase chain reaction (PCR) assay. After the
      glioma C6 cells were transduced by Adtk at different multiplicity of infection
      (MOI) and exposed to different concentrations of ACV or gancyclovir (GCV), the
      cell survival curves were studied, and the cell surface was observed with
      scanning electronic microscopy (SEM). C6 gliomas in vivo at different inoculation
      days were injected with Adtk intratumorally and ACV intraperitoneally daily, and
      the survival duration and histologic changes of the rats were observed. RESULTS:
      The infectious Adtk virions had a suicide effect which was enhanced with the
      increase in MOIs of Adtk and ACV doses along with bystander effect. Under
      scanning electronic microscope, special pathologic changes were observed. ACV had
      a similar effect as GCV but a higher dose was used. The survival duration in day
      3, day 6 and day 8 groups exceeded 90 days, and the rats in day 10 group survived
      28.5 +/- 4.6 days, but the survival duration in untreated C6 group and AdLacZ/ACV
      (adenovirus-mediated LacZ/ACV) treated group were 16.8 +/- 3.1 and 14.0 +/- 2.2
      days respectively. CONCLUSION: Adtk/ACV system can effectively kill the rat brain
      gliomas in vitro and in vivo.

PMID- 11245063
TI  - The influence of impaired microvasculature on regional blood flow of the spinal
      cord after microsurgery.
AB  - OBJECTIVE: To further investigate the impact of impaired microvasculature of
      spinal cord and its physiological compensation on postoperative morbidity after
      intramedullary microsurgery. METHODS: In 120 cats, the segmental anterior
      longitudinal spinal arteries (ALSA), the posterior longitudinal spinal arteries
      (PLSA), and the unilateral radiculomedullary arteries (RMA) were selectively
      coagulated in different patterns. Hydrogen electrode technique was used to detect
      the changes of regional blood flow of the spinal cord at different segments.
      Benzidine dihydrochloride (BDHC) staining was used to observe the microvascular
      pattern of the spinal cord, tetrazolium chloride (TTC) staining was applied to
      morphometric analysis of the ischemic area, and hematoxylin-eosin staining was
      applied to histologic examination. RESULTS: When the segmental ALSA was injured,
      the blood flow of the gray matter and white matter decreased greatly. Since the
      central arteries were the terminal blood supply arteries, no compensation
      occurred after the injury. The blood flow of the segment below the impaired
      segment hardly changed, indicating that the direction of the blood flow in ALSA
      altered to adapt the changes of the microvasculature. Injury to the unilateral
      PLSA and RMA at both cervical and lumbar area only caused a minor decrease in the
      regional blood flow, unless the perimedullary arterial system was considerably
      injured. In the thoracic medullary segment, the sparse microvasculature was the
      main cause for the segment vulnerable to ischemia and infarction. This was caused
      by not only the rarity of RMA as an anatomic factor, but also the small number
      and low activity of the neurons at this area. After microsurgery, the impairment
      and decompensation of the microvasculature were closely related to the ischemic
      volume of and pathological changes in the spinal cord. CONCLUSION: The impairment
      and decompensation of microvasculature after microsurgery are the rudimentary
      causes of spinal cord ischemia. During operation, one should protect the terminal
      arteries to decrease the severity of injury to the perimedullary system, and do
      the best to avoid disturbance of microvasculature to accelerate the recovery of
      postoperative ischemia and neurological dysfunction of the spinal cord.

PMID- 11245064
TI  - Effects of beta-amyloid peptide on transient outward potassium current of acutely
      dissociated hippocampal neurons in CA1 sector in rats.
AB  - OBJECTIVE: To explore the mechanism of beta-amyloid peptide (beta-AP) in
      Alzheimer's disease at ionic channel level. METHODS: Hippocampal CA1 neurons of 7
      21 days' rats were acutely dissociated and the effects of beta-AP on transient
      outward potassium current were observed by a whole-cell recording patch clamp
      technique. RESULTS: beta-AP can significantly block transient potassium current
      in dose-dependent, time-dependent and partly voltage-dependent manners.
      CONCLUSION: beta-AP may decrease the membrane conductance of K+ channels in
      hippocampal neurons, playing an important role in the pathophysiological
      mechanism of Alzheimer's disease.

PMID- 11245065
TI  - Phrenic nerve conduction and diaphragmatic motor evoked potentials: evaluation of
      respiratory dysfunction.
AB  - OBJECTIVE: To investigate preliminarily the value of phrenic nerve conduction
      (PNC) and diaphragmatic motor evoked potentials (MEPs) in the evaluation of
      various respiratory dysfunction (RDF). METHODS: Thirty-four patients with various
      RDF, (19 patients with neurogenical diseases and 15 patients with respiratory
      disorders) were investigated. Fifty healthy volunteers served as controls. The
      phrenic nerve was cutaneously stimulated by electrical pulse current at the
      midpoint of the posterior border of the sternomastoid muscle, and the
      diaphragmatic muscle compound action potentials (DCAP) were recorded between the
      7th and 8th intercostal space and xiphoid process. When the magnetic transcranial
      stimulation (MTS) of the cortex was given, the recordings were made under the
      condition of maximal deep inspiration. RESULTS: All patients with myopathies had
      normal PNC. The patients with Guillain Barre syndrome (GBS), hereditary motor and
      sensory neuropathy (HMSN) and myasthenic crisis had abnormal PNC. The findings in
      PNC studies remarkably correlated with RDF, while serial examinations were
      performed in the patients with GBS and myasthenia gravis (MG). In 7 patients with
      sleep apnea syndrome (SAS), 4 had abnormal PNC, and 2 of 3 patients with chronic
      obstructive pulmonary diseases (COPD), and 1 of 5 patients with chest tightness
      or breathlessness on the supine position showed decreased amplitude. When MEPs
      were recorded, 3 of 5 patients showed abnormal SAS (1 had no response, 2 lower
      amplitude). Three patients with COPD had normal MEP. CONCLUSIONS: PNC studies
      could not only evaluate neuromuscular RDF and predict the outcome of diseases,
      but also supply additional information about diaphragmatic dysfunction for the
      RDF caused by respiratory disorders. The results of PNC and diaphragmatic MEP may
      differentiate the types of SAS.

PMID- 11245066
TI  - Mitochondrial gene defect in patients with chronic progressive external
      ophthalmoplegia.
AB  - OBJECTIVE: To detect the gene defect of mitochondrial DNA (mtDNA) from skeletal
      muscles in 2 patients with chronic progressive external ophthalmoplegia (CPEO).
      METHODS: After extraction of mtDNA, Southern hybridization was performed after
      restrictive digestion by Pvu II, EcoRI, Hind III, and Sacl. Then, we carried out
      polymerase chain reaction (PCR) and the enzyme digestion of the PCR products.
      Finally, mtDNA sequencing was done by automatic DNA sequence analyzer. RESULTS:
      In case 1, a 5 kb deletion was found by Southern blot analysis and PCR. And
      dosage analysis showed a heteroplasmic change with 44% mtDNAs deleted. In case 2,
      PCR plus restriction endonuclease Pvu II digestion demonstrated a mutation which
      was confirmed by DNA sequencing to be a single base substitution (T-->C) inducing
      a novel Pvu II site around 10,909 on mtDNA sequence. The laser image analyzer
      measurement revealed the mutation was almost homologous (99.4% mutant).
      CONCLUSIONS: In case 1, a 5 kb deletion found in mtDNA is called "common
      deletion" according to the literature. In case 2, a novel Pvu II site was found.
      It seems to be a de novo point mutation affecting ND4 in published CPEO research
      and is first reported in Chinese population. This point mutation does not induce
      an amino acid(Phe) change according to the published human mitochondrial genetic
      code as well as the mtDNA sequence. Whether it affects the translation efficiency
      or transportation of signals between mitochondrial and nuclear genome needs
      further studies.

PMID- 11245068
TI  - Alpha-1 adrenergic receptors in liver plasma membranes of cirrhotic patients with
      portal hypertension: a quantitative study.
AB  - OBJECTIVE: To investigate the changes of alpha-1 adrenergic receptors in
      cirrhotic liver and the relationship between the changes and the pathogenesis of
      portal hypertension. METHODS: The concentration and affinity of alpha-1
      adrenergic receptors in the liver plasma membranes of posthepatitic cirrhotic
      patients with portal hypertension were quantitatively measured using radioligand
      binding analysis. RESULTS: Compared with 8 controls without hepatic pathological
      changes, the maximal binding capacity (Bmax) of 9 posthepatitic cirrhotic
      patients decreased (129.1 +/- 12.0 vs 142.1 +/- 14.1 fmol/mg protein, P > 0.05),
      dissociation constant (Kd) values increased (0.3945 +/- 0.0974 vs 0.2382 +/-
      0.0548 nmol/L, P < 0.01), and the receptor maximal content (RMC) decreased (417.4
      +/- 76.8 vs 739.9 +/- 167.6 fmol/g liver, P < 0.01). CONCLUSIONS: The decreased
      concentration and affinity of alpha-1 adrenergic receptors may play an important
      role in the metabolic disturbances of catecholamines often seen in some cirrhotic
      patients, and have implications in the pathogenesis of portal hypertension.

PMID- 11245067
TI  - Serum levels of epinephrine and norepinephrine in cirrhotic patients with portal
      hypertension.
AB  - OBJECTIVE: To investigate the role of catecholamines in the pathogenesis of
      portal hypertension. METHODS: Serum epinephrine (E) and norepinephrine (NE)
      concentrations in the peripheral vein, portal vein and superior vena cava (SVC)
      were measured by high pressure liquid chromatography in 38 portal hypertensive
      patients, 28 idiopathic hypertensive patients and 34 controls, respectively.
      RESULTS: Peripheral venous E concentrations in portal hypertensive patients and
      controls were 57.5 +/- 37.4 ng/L and 23.5 +/- 11.2 ng/L, respectively (P < 0.01),
      and peripheral venous NE concentrations were 451.1 +/- 381.2 ng/L and 183.0 +/-
      83.3 ng/L, respectively (P < 0.01). Compared with controls, peripheral venous E
      (54.9 +/- 39.9 ng/L vs 23.5 +/- 11.2 ng/L, P < 0.01) and NE (524.3 +/- 219.9 ng/L
      vs 183.0 +/- 83.3 ng/L, P < 0.01) in idiopathic hypertensive patients were also
      significantly increased. E and NE in SVC, portal vein and peripheral artery in
      portal hypertensive patients were also increased, but only the elevation of E in
      SVC was statistically significant (207.2 +/- 55.4 ng/L vs 83.7 +/- 46.7 ng/L, P <
      0.05). CONCLUSION: Our results reveal significant metabolic disorders of E and NE
      in portal hypertensive patients, which may play an important role in the
      pathogenesis of portal hypertension.

PMID- 11245069
TI  - Is there any relation between ischemic cerebrovascular disease and extracranial
      internal carotid stenosis?
AB  - OBJECTIVES: To confirm the existence of plaque or stenosis in the extracranial
      carotid arteries of patients with transient ischemia attack (TIA) or stroke, and
      to analyze the prevalence of extracranial carotid atherosclerotic stenosis, as
      well as the relation between the hemispheric symptoms and the degree of stenosis.
      METHODS: From January 1995 to March 1996, 188 patients underwent routine carotid
      artery duplex scan at Zhongshan Hospital, Shanghai. Of the 188 patients, 134 had
      TIA or stroke in the carotid territory during the previous 12 months, 54 were
      with peripheral arterial occlusive disease (PAOD). All patients were divided into
      three groups, that is, stroke/TIA group (Group 1, n = 128), PAOD group (Group 2,
      n = 36), and stroke/TIA + PAOD group (Group 3, n = 24). The classification of
      degree of stenosis in our study was as same as that applied by North American
      Symptomatic Carotid Endarterectomy Trial (NASCET) and European Carotid Surgery
      Trial (ECST). RESULTS: A total of 376 internal carotid arteries were examined by
      duplex scanning in this study. The prevalence of severe stenosis in the three
      groups was 12.5%, 8.3% and 37.5% separately. The severity of stenosis had a close
      relation with patients' symptoms (P < 0.01). CONCLUSIONS: Patients with stroke or
      TIA have atherosclerotic plaques in the carotid arteries. The prevalence of
      extracranial carotid stenosis is comparable to that reported in the literature.
      PAOD may be helpful to identify patients at high risk for severe carotid
      stenosis. Carotid duplex scanning should be performed as a routine examination
      for patients with stroke, TIA, and PAOD.

PMID- 11245070
TI  - The role of gut as a cytokine-generating organ in remote organ dysfunction after
      intestinal ischemia and reperfusion.
AB  - OBJECTIVE: To test the hypothesis that in a rat model of acute intestinal
      ischemia/reperfusion injury, endotoxemia from the gastrointestinal tract would
      play a role in mediating tumor necrosis factor (TNF) response and remote organ
      dysfunction. METHODS: Wistar rats underwent 45 minutes of superior mesenteric
      artery occlusion followed by 6 hours of reperfusion. The rats were treated
      intravenously with either TNF monoclonal antibody (MoAb) or saline solution 90
      minutes prior to the onset of ischemia. RESULTS: Significant elevation of plasma
      TNF level in both portal and systemic circulation was detected immediately after
      the onset of reperfusion. The level peaked at two hours after reperfusion (P <
      0.01). Similarly, a remarkable TNF mRNA expression in the intestine in controls
      was detected at 0.5 hour post-reperfusion, and sustained a marked elevation
      throughout the observation period (P < 0.05-0.01). TNF elevation was found
      associated with gut-origin endotoxemia, and the maximal TNF response occurred
      approximately 0.5-2 hours after the initial appearance of endotoxin in the portal
      vein. Concomitantly, multiple organ dysfunction in response to local ischemic
      insult was also observed in untreated controls upon reperfusion, but it was
      significantly attenuated by pretreatment with MoAb against TNF. CONCLUSIONS:
      Intestinal injury can result in the gut becoming a cytokine-liberating organ. The
      escape of endotoxin and bacteria from the gut may be responsible for the TNF
      expression and release, which would be an important mechanism underlying
      pathophysiological alterations associated with intestinal ischemia/reperfusion
      injury.

PMID- 11245071
TI  - Experimental study on pathogenicity of precore mutants in Hepadnaviridae.
AB  - OBJECTIVE: To study the replicative competency and pathogenicity of precore gene
      mutants of duck hepatitis B virus (DHBV) in the duck model. METHODS: Three site
      directed point mutations in the precore region of cloned DHBV were constructed.
      Head-to-tail dimers were formed. The three plasmids were named: pEDM1-2
      (initiation codon ATG mutated to TTG), pEDM2-2 (an "A" was inserted down stream
      of codon 12, leading to frame shift in the distal end of precore region), pEDM3-2
      (codon 38 was changed from TAT to TAA, leading to a stop codon at the 3'-end).
      Mutants and wild-type cloned DNA dimers were first separately used to transfect
      LMH cells (a chicken hepatoma cell line) and viruses were collected from
      supernatant and used to infect 6 one-day-old ducklings per group. Serum duck
      hepatitis B surface antigen (DHBsAg) and DHBV DNA were assayed. Six weeks after
      infection, ducks were killed and liver tissues were studied for histopathological
      changes. RESULTS: After transfection, pEDM1-2, pEDM2-2 and pEDM3-2 expressed
      similar level of DHBsAg. Replication of pEDM1-2 and pEDM3-2 was similar to that
      of the wild type clone, while pEDM2-2 replicated at a significantly decreased
      level. Infection study employing the supernatant of transfected cells was as
      follows: pEDM1-2 infected 5/6 ducklings, pEDM2-2 non infected, pEDM3-2 infected
      2/6 ducklings, wild type virus infected 6/6 ducklings. Positive serum samples
      from both pEDM1-2 and pEDM3-2 were at a lower serum DHBV level compared to that
      of the wild type virus. Pathological changes were more significant in pEDM3-2
      infected duck livers, with numerous inflammatory cells in portal tract and
      infiltration into parenchyma. CONCLUSIONS: Mutations in the initiating codon or
      generation of a stop codon at the 3'-end of the precore region resulted in
      decreased replication competency of DHBV, while frame-shift mutation of the
      precore region, covering the epsilon encapsidation signal abolished the
      replication of DHBV. When the mutants replicated in hosts, more severe
      pathological changes were observed in ducks infected with mutant harboring a stop
      codon at the 3'-end. Data suggest that replicative-competent DHBV precore mutant
      can be more pathogenic than wild-type DHBV.

PMID- 11245072
TI  - Induction of anti-DNA antibodies by immunization with activated lymphocytes and
      active chromatin.
AB  - OBJECTIVE: To investigate the primary autoantigens which contribute to the
      production of anti-DNA antibodies. These antibodies are serological hallmark and
      pathogenic factor of systemic lupus erythematosus (SLE). METHODS: Nonautoimmune
      predisposed BALB/c mice were immunized with concanavalin A (Con A) activated,
      lipopolysaccharide (LPS) activated and nonactivated syngeneic spleen cells.
      Nuclei and chromatin from activated/nonactivated lymphocytes were isolated and
      syngeneic mice were immunized. Sera were taken after the third immunization. IgG
      anti-dsDNA antibody was determined by ELISA (calf thymus DNA treated with S1
      nuclease was used as the coated antigen). The glomerular IgG deposition was
      observed by immunofluorescence one month after the third immunization. RESULTS:
      Con A activated T cells and LPS activated B cells induced anti-double stranded
      (ds) DNA antibody in syngeneic nonautoimmune BALB/c mice and formed the
      glomerular IgG deposition. Further studies showed that active chromatin isolated
      from activated lymphocytes induced anti-ds DNA antibody, but not resting
      chromatin isolated from nonactivated lymphocytes. CONCLUSIONS: Activated
      lymphocytes and their active chromatin could be the autoimmunogen(s) driving the
      anti-dsDNA antibodies. The change of chromatin's antigenicity by environmental
      factors and genetic background may be the common pathway to SLE pathogenesis.

PMID- 11245073
TI  - Polymorphism of DXS102 locus in Chinese population and its application to gene
      diagnosis in hemophilia B family.
AB  - OBJECTIVE: To establish the polymorphism of DXS102 locus from Xq26.3-27.1 in
      Chinese population for the gene diagnosis in Hemophilia B family. METHODS: DNA
      was extracted from blood samples obtained from Shanghai unrelated volunteer
      donors with phenol-chloroform method. A total of 23x chromosomes (154 from
      females, 80 from males) were studied. A hemophilia B family in which a hemophilia
      B patient has received gene therapy was analyzed. The polymorphism of DXS102
      locus in Chinese population was determined with amplified fragment length
      polymorphisms assay (Amp-FLP), denaturing polyacrylamide gel electrophoresis,
      silver stain detection. Short tandem repeats (STRs) linkage analysis was used to
      conduct gene diagnosis in hemophilia B family. RESULTS: Eight alleles were found
      at DXS102 locus, of which two alleles were first reported. The repeated number of
      AC dinucleotide ranges from 13 to 21. And the values of the observed
      heterozygosity, calculated heterozygosity and polymorphism information
      content(PIC) were 0.87, 0.80, 0.80 respectively. It was also found that the
      difference of the allele frequencies of DXS102 in Chinese and European
      populations was significant. By using the linkage analysis of the DXS102 locus, a
      family with a hemophilia B patient receiving gene therapy in 1994 was analyzed
      and meanwhile a carrier in that family was then detected. CONCLUSIONS: The
      polymorphism of DXS102 locus reveals significant difference between Chinese and
      European populations. DXS102 locus can be used as a promising marker for gene
      diagnosis in hemophilia B family.

PMID- 11245075
TI  - Laparoscopic retroperitoneal lymph node dissection in clinical stage I
      nonseminomatous germ cell tumor: a minimal invasive alternative.
AB  - OBJECTIVE: To evaluate modified laparoscopic retroperitoneal lymph node
      dissection (LRPLND) performed for stage I nonseminomatous germ cell tumor.
      METHODS: Between December 1993 and January 1996, modified unilateral laparoscopic
      retroperitoneal lymph node dissection was performed on 13 patients with
      nonseminomatous germ cell tumor of the testis. In 8 patients, the tumor was on
      the right side, and in 5, on the left. RESULTS: The procedure was completed in 12
      patients at a mean operating time of 292 min (range: 210-400 min). The mean
      estimated blood loss was 250 ml. The mean hospital stay was 6.4 days. Conversion
      to open surgery was required in one patient because of an uncontrollable venous
      bleeding. No other major complications occurred. Antegrade ejaculation was
      preserved in 10 patients, and the last 3 patients have not yet been addressed
      now. CONCLUSIONS: Our results demonstrate that LRPLND is an accurate and reliable
      staging procedure with low morbidity, which allows quick patient discharge and
      rapid return to normal activity. For further evaluation, long follow-up in larger
      groups of patients is required.

PMID- 11245074
TI  - Serological diagnosis of nasopharyngeal carcinoma by enzyme linked immunosorbent
      assay: optimization, standardization and diagnostic criteria.
AB  - OBJECTIVES: To produce an enzyme linked immunosorbent assay (ELISA) to detect
      antibodies against Epstein Barr virus (EBV) specified nuclear antigen 1 (EBNA 1)
      and the 18 kD EBV matrix protein, and to determine and optimize its sensitivity
      and specificity for the diagnosis of nasopharyngeal carcinoma (NPC). METHODS: We
      used a combination of highly purified glutathione transferase fusion proteins of
      the 40 kD carboxy domain of EBNA1 and the 18 kD EBV matrix protein for coating
      ELISA plates. In three separate studies, we tested for IgA antibodies in serum
      specimens from 28 EBV seronegative donors, 284 EBV seropositive donors and 160
      newly diagnosed NPC patients. By comparing the sensitivity and specificity of
      diagnosis obtained for different cutoff values, we derived several quantitative
      parameters to evaluate assay performance, establish objective diagnostic criteria
      which optimize the intrinsic diagnostic capability of the assay and assess the
      significance of individual test results, respectively. Optimum cutoff optical
      density (OD) is defined as the cutoff OD where sensitivity of the assay equals
      its specificity, and resolution of the assay is indicated by the value of
      sensitivity (or specificity) determined at the optimum cutoff OD. Diagnosis of
      NPC was achieved by setting a cutoff zone at +/- 20% of this value. RESULTS: All
      the EBV seronegative donors tested were not reactive, and most of the EBV
      seropositive donors were weakly reactive, while the majority of NPC patients were
      moderately or strongly reactive. While the assay was thus shown to be specific
      for EBV, there was an overlap in the level of these serum antibodies between few
      individuals of the two latter groups. It was shown that the assay performed
      equally well in two separate studies conducted under different testing conditions
      and using different collections of sera in that assay resolution determined on
      these occasions were 86% and 87% respectively. Diagnosis of NPC can be achieved
      at the same expected sensitivity of 89% and 83% determined at the lower and upper
      limits of the cutoff zones, with the corresponding values of specificity being
      78% and 91%. It was further shown in the third study that resolution of the assay
      can be increased to 90% using an assay produced with a higher concentration of
      the same antigens, and that diagnosis of NPC can be achieved at a higher
      sensitivity ranging between 86% and 95% at a corresponding specificity of 93% and
      86%. CONCLUSIONS: After optimization and standardization, the ELISA can achieve a
      sensitivity ranging from 86% to 95%, with corresponding specificities of 93% and
      86% respectively for the diagnosis of NPC.

PMID- 11245076
TI  - Evaluation of left ventricular function with cine magnetic resonance four
      chamber/multiple slice multiple phase sequence.
AB  - OBJECTIVE: To investigate the value of cine magnetic resonance(MR) in
      determination of cardiac function by using four chamber/multiple slice multiple
      phase (4CH/MSMP) sequence. METHODS: In 18 healthy subjects, several indices of
      left ventricular function were measured by using cine MR 4CH/MSMP sequence, and
      the correlation of the results was compared with ultrasound cardiography by t
      test. RESULTS: In the measurement of left ventricular short diameter, left
      ventricular posterior wall thickness, internal ventricular septum thickness, left
      ventricular end diastolic and end systolic volume, the values of cine MR 4CH/MSMP
      sequence correlated well with those of echocardiography. The gamma value was
      between 0.88 and 0.99. CONCLUSION: The cine MR 4CH/MSMP sequence may be
      considered an important noninvasive modality for accurate assessment of cardiac
      function.

PMID- 11245077
TI  - Growth regulation of ovarian cancer cell line HO-8910 by transforming growth
      factor beta 1 in vitro.
AB  - OBJECTIVE: To further understand the role of growth regulation of human ovarian
      cancer cells by transforming growth factor (TGF) beta 1. METHODS: The cell
      proliferation, cAMP synthesis, gene expression, and induction of programmed cell
      death (PCD) in human epithelial ovarian cancer cell line HO-8910 cells exposed to
      TGF beta 1 in vitro were studied. RESULTS: TGF beta 1 inhibited cell growth and
      DNA synthesis, and induced G0/G1 arrest in cell cycle. It could also trigger PCD
      in cells. This induction of PCD may occur within G0/G1 phase. Meanwhile, the
      assay also showed that TGF beta 1 could inhibit the mRNA expression of c-myc,
      EGFR and TGF beta 1 genes in cells. CONCLUSIONS: TGF beta 1 can not only act as
      an autocrine to inhibit cell proliferation, but also trigger PCD in HO-8910
      cells. These functions may be fulfilled through some specific signal transduction
      pathways.

PMID- 11245078
TI  - Expression of type-I collagen and matrix metalloproteinase-9 mRNA in bone of
      castrated adult female rats: effects of estrogen.
AB  - OBJECTIVES: To elucidate the molecular changes of bone collagen during the
      development of postmenopausal osteoporosis and to investigate the molecular
      effects of estrogen replacement. METHODS: An adult ovariotomy rat model was used.
      Type-I collagen and matrix metalloproteinase-9 (MMP-9) expressions in bone
      tissues of rats treated by sham surgery (SH), bilateral ovariotomy (OVX) and OVX
      with estradiol (OVX-E2) were analysed at mRNA level by using dot blot technique.
      The distribution of mRNA of these two genes in bone tissues was studied by in
      situ hybridization. RESULTS: The expression levels of both type-I collagen and
      MMP-9 in bone tissues of OVX rats were higher than those of SH group, while
      treated with estradiol, the expression of both genes declined to some degree. In
      situ hybridization showed that type-I collagen mRNA located in osteoblasts,
      whereas MMP-9 was mainly expressed in osteoclasts, some lining cells on bone
      surface, and some mononuclear cells in bone marrow. CONCLUSIONS: The reduction of
      high bone turnover in osteoporotic bone tissues induced by estrogen replacement
      may result from alterations in gene expression related to bone formation and bone
      resorption. These alterations are consistent with the changes observed previously
      by histomorphometry and biochemical markers of bone metabolism on OVX animals and
      postmenopausal osteoporosis.

PMID- 11245079
TI  - Mechanism of allyl chloride-induced cytoskeletal injury to nerve cells.
AB  - OBJECTIVE: To dissect the molecular mechanism of toxic neuropathy induced by
      allyl chloride (AC). METHODS: Fluorescence molecular probe (Fura-2/AM), electron
      probe X-ray microprobe analysis (EPMA) and biochemical methods were used to
      determine the concentrations of cytosolic free Ca2+, the contents of
      intracellular Ca2+ percentage, Ca(2+)-free calmodulin (CaM), the activity of
      Ca2+/CaM-dependent protein kinase II (Ca2+/CaM-PK II), and cytoskeletal protein
      synthesis in chicken embryo brain cells induced by AC. RESULTS: The contents of
      Ca2+ percentage, the concentrations of cytosolic free Ca2+, and the activities of
      Ca2+/CaM-PK II in the cells were increased significantly as AC was added (P <
      0.01). However, the content of Ca(2+)-free CaM and the synthesis of cytoskeletal
      proteins were markedly decreased (P < 0.01). CONCLUSION: The results suggest that
      one of the mechanism of AC-induced cytoskeletal injury in vitro might be related
      to the elevation of intracellular Ca2+, activated CaM and Ca2+/CaM-PK II.

PMID- 11245080
TI  - Immunological approaches to the breakdown of hepatitis B viral persistence.

PMID- 11245081
TI  - A suggestion for unification of present limb lead systems into a single "F" lead
      system.
AB  - In this paper it is intended to unify the standard lead and the augmented
      unipolar limb lead (aV lead) system into a single lead system. Viewing from the
      angle of lead axes, the standard leads and the aV leads are not only reflecting
      the frontal plane vector, but are also actually complementary to each other. By
      now it has become quite obvious that they not only can, but also should be
      unified into a single system. Viewing these six leads (from standard lead and aV
      lead systems), starting from aVL, lead I, reversed aVR, lead II, aVF to lead III,
      an arc including approximately 150 degrees is formed. It is suggested that this
      unified system may be called "F" system with each of the above leads renamed as
      F1-F6 leads, respectively, since they are all reflecting the vectors of the
      frontal plane. In this F-lead system each lead is approximately 30 degrees apart.
      If such a system would be adopted it is only necessary to time the amplitude of
      the P, QRS and T of aV lead by 1.15 (a figure calculated by vector analysis). If
      this suggestion is widely adopted there will be only a F lead system for the
      frontal vectors and the present V system for the "horizontal" vectors in the
      electrocardiogram.

PMID- 11245082
TI  - Pseudobacteremia with amoxycillin-clavulanic acid-resistant Escherichia coli
      traced to cross-contamination during blood culture processing.
AB  - Escherichia coli has seldom been reported to cause pseudobacteremia. The
      investigation of an outbreak of amoxycillin-clavulanic acid-resistant E. coli
      pseudobacteremia is described. Seventeen cases occurred over a five-day period.
      The source of the E. coli was traced to the blood culture specimen of a patient
      (index patient) with genuine bacteremia as a result of urinary tract infection.
      The other 16 case-patients had pseudobacteremia which was found to be the result
      of cross-contamination during subculture of blood specimens. The E. coli strain
      was carried over from the culture bottle of the index patient, through the
      contaminated gloved hands of a technician to the culture bottles of the other 16
      cases. Although the pseudobacteremia occurred over a five-day period, they all
      resulted from cross-contamination during blood culture processing within one day.
      An early outbreak investigation was prompted by the unusual finding of
      amoxycillin-clavulanic acid resistance in the case E. coli isolates in a short
      period. The relatedness of the E. coli strains from the 17 cases was confirmed by
      arbitrary-primed polymerase chain reaction. Clinicians should be alerted to the
      possibility of a blood E. coli isolate being a contaminant despite its
      predominant role as a true pathogen.

PMID- 11245083
TI  - Acupuncture: pain management coupled to immune stimulation.
AB  - The phenomenon of acupuncture is both complex and dynamic. Recent information
      demonstrates that acupuncture may exert its actions on pain and immune processes.
      The coupling of these two systems occurs via common signaling molecules, i.e.,
      opioid peptides. In this regard, we surmise that opioid activation leads to the
      processing of opioid peptides from their precursor, proenkephalin, and the
      simultaneous release of antibacterial peptides contained within the precursor as
      well. Thus, central nervous system pain circuits may be coupled to immune
      enhancement. Furthermore, acupuncture needle manipulation elicited signal
      increases bilaterally in the region of the primary and secondary somatosensory
      corticies in human brain as determined by magnetic resonance imaging. The maps
      reveal marked signal decreases bilaterally in multiple limbic and deep gray
      structures including the nucleus accumbens, amygdala, hypothalamus, hippocampus,
      and ventral tegmental area. Taken together, we surmise a major central nervous
      system pathway as well as local pain and immune modulation during acupuncture.

PMID- 11245085
TI  - Secretoneurin and neurogenic inflammation.
AB  - AIM: Review of evidence that the 33-amino-acid polypeptide secretoneurin, which
      is generated by proteolytic cleavage of secretogranin II, plays a role in
      neurogenic inflammation. METHODS: Survey of the literature using a MEDLINE search
      database. RESULTS: Secretoneurin is synthesized in spinal ganglia, transported
      through the dorsal roots and stored in the axon terminals of primary afferent
      neurons. Investigations using capsaicin suggest that secretoneurin functions as
      an excitatory transmitter. Secretoneurin specifically activates various cell
      functions including the chemotactic migration of monocytes, eosinophils,
      fibroblasts, smooth muscle cells, and endothelial cells, which suggests that the
      peptide may modulate inflammatory reactions. Secretoneurin receptors have been
      functionally characterized. They are G-proteins linked and effects are abrogated
      by inhibition of protein kinase C. CONCLUSION: With actions as diverse as those
      seen with other mediators such as tachykinins, secretoneurin may be considered
      another sensory neuropeptide with modulatory potential in neurogenic
      inflammation.

PMID- 11245084
TI  - Yawning: role of hypothalamic paraventricular nitric oxide.
AB  - Yawning is a phylogenetically old, stereotyped event that occurs alone or
      associated with stretching and/or penile erection in humans, in animals from
      reptiles to birds and mammals, under different conditions. Several
      neurotransmitters and neuropeptides are involved in its control at the central
      level. One of these at the level of the paraventricular hypothalamic nucleus
      (PVHN) is nitric oxide (NO). First, NO synthase inhibitors injected into this
      hypothalamic nucleus prevent yawning induced by dopamine agonists, oxytocin or N
      methyl-D-aspartic acid (NMDA), which induce yawning by activating PVHN
      oxytocinergic neurons projecting to extra-hypothalamic brain areas. The
      inhibitory effect of NO synthase inhibitors was not observed when these compounds
      were given concomitantly with L-arginine, the precursor of NO. Second, dopamine
      agonists, NMDA and oxytocin given at doses that induce yawning, increase NO
      production in the PVHN, as determined by in vivo microdialysis. Conversely, the
      opiate morphine, which prevents yawning induced by dopamine agonists, oxytocin
      and NMDA, also prevents the increase in the paraventricular NO production induced
      by these compounds. Third, NO donors, such as nitroglycerin, sodium nitroprusside
      and hydroxylamine, induce yawning when injected into the PVHN apparently by
      activating oxytocinergic transmission. Since guanylate cyclase inhibitors and NO
      scavengers (hemoglobin) injected into the PVHN do not prevent drug-induced
      yawning, nor 8-Br-cGMP injected into the PVHN induces this behavioral response,
      it is likely that NO acts as an intracellular rather than an intercellular
      modulator inside the PVHN oxytocinergic neurons in which NO is formed to
      facilitate the expression of this phylogenetically old event by guanylate cyclase
      independent mechanisms.

PMID- 11245086
TI  - Inhibitory effect of recombinant TGF alpha-PE40 on vascular smooth muscle cell
      proliferation.
AB  - AIM: To study inhibitory effect of recombinant transforming growth factor alpha
      Pseudomonas exotoxin fusion protein (TP40) on proliferation of the cultured
      vascular smooth muscle cells (SMC). METHODS: Expression of epidermal growth
      factor receptor (EGFR) mRNA and EGFR in cultured proliferating and quiescent SMC
      was analyzed with Northern blot and immunohistochemistry. Inhibitory effects of
      TP40 on SMC proliferation and protein synthesis were analyzed with crystal violet
      staining and [3H]leucine incorporation. Competition assays were performed by the
      addition of 100-fold excess of EGF. RESULTS: Expression of EGFR mRNA and EGFR in
      rapidly proliferating SMC increased than that in quiescent SMC. When the
      concentration of TP40 was 10 or 100 micrograms.L-1, inhibitory effects of TP40 on
      rapidly proliferating SMC proliferation and protein synthesis were much higher
      than that on quiescent SMC (P < 0.01), and the IC50 of [3H]leucine incorporation
      against rapidly proliferating and quiescent SMC were 8.01 (5.05-12.69) and 121.95
      (90.98-163.47) micrograms.L-1. Excess EGF completely blocked inhibitory effects
      of TP40. CONCLUSION: The rapidly proliferating SMC express EGFR at a high level.
      TP40 selectively inhibited the proliferation of rapidly proliferating SMC. The
      cytotoxic effects of TP40 were specifically mediated by EGFR.

PMID- 11245087
TI  - 99mTc-MIBI single-photon emission-computed tomography in diagnosis of lung cancer
      and mediastinal metastasis lymph nodes.
AB  - AIM: To evaluate the value of technetium-99m-methoxyisobutyl isonitrile (99mTc
      MIBI) single-photon emission-computed tomography (SPECT) in diagnosis of lung
      cancer and in preoperative prediction of mediastinal metastasis lymph nodes.
      METHODS: After the chest image of 99mTc-MIBI SPECT, fifty patients (40M, 10F; age
      56 a +/- 11 a) diagnosed "lung field shadow" underwent the lung focus and
      mediastinal lymph nodes resection. As the golden standard, pathologic diagnosis
      was used to evaluate the role of preoperative 99mTc-MIBI SPECT. RESULTS: The
      sensitivity, specificity, and accuracy of 99mTc-MIBI SPECT were 93%, 50%, and
      86%, respectively in lung cancer and 81%, 95%, and 88%, respectively in
      mediastinal metastasis lymph node. The results were also better than those of
      chest scan with CT. CONCLUSION: The 99mTc-MIBI SPECT is a useful and noninvasive
      method for diagnosing lung cancer and predicting mediastinal metastasis lymph
      nodes, which will guide the surgeon to resect the mediastinal metastasis lymph
      nodes.

PMID- 11245088
TI  - Effects of S-21007, a potent 5-HT3 partial agonist, in mouse anxiety.
AB  - AIM: To study the effect of S-21007, a 5-HT3 partial agonist in different animal
      models of anxiety in mice. METHODS: S-21007 effects were evaluated in the
      behavior tests after intraperitoneal and oral acute treatment or in the
      light/dark test after both acute and chronic treatments. RESULTS: S-21007
      presented anxiolytic-like properties after acute administration in the light/dark
      box test, the mirrored chamber test, and the elevated plus-maze at low doses 10
      ng.kg(-1)-100 micrograms.kg-1, 1-100 micrograms.kg-1 and 10-100 micrograms.kg-1,
      respectively. In the light/dark box test, S-21007 was active orally after acute
      treatment at 100 ng.kg(-1)-10 mg.kg-1 and after chronic treatment (14 d) at 1-10
      micrograms.kg-1. S-21007 was devoid of sedative or stimulatory effects.
      CONCLUSION: S-21007 exhibited anxiolytic-like properties. The mechanism of action
      may be a desensitization of 5-HT3 receptor or an antagonist activity on the 5-HT3
      receptors.

PMID- 11245089
TI  - Effects of modafinil and amphetamine on sleep-wake cycle after sleep deprivation
      in cats.
AB  - AIM: The effects of modafinil and amphetamine on sleep-wake cycle and cortical
      power spectrum were assessed in the cats before and after sleep deprivation.
      METHODS: The sleep deprivation in the cats was used with the water tank
      technique. Cats were administrated with modafinil (5 mg.kg-1 p.o.) or amphetamine
      (1 mg.kg-1) before and after sleep deprivation. RESULTS: The waking effect of 8
      10 h induced by modafinil before and after sleep deprivation was similar and was
      not followed by an increase in sleep rebound. On the contrary, the arousal effect
      about 8 h evoked by amphetamine after sleep deprivation was less lasting than
      that of 10-12 h observed in normal conditions and followed by an amplified
      rebound in both deep slow wave sleep and paradoxical sleep. CONCLUSION: These
      results suggest the efficiency of modafinil against somnolence and hypersomnia
      without increasing subsequent sleep.

PMID- 11245090
TI  - Bepridil inhibition of sodium current in rat hippocampal CA1 neurons.
AB  - AIM: To study the effects of bepridil on sodium current in rat hippocampal
      neurons. METHODS: All experiments were performed on acutely isolated hippocampal
      pyramidal neurons by means of whole-cell patch-clamp techniques. Recording media
      contained ion channel blockers to allow the selective activation of voltage
      dependent sodium currents. RESULTS: Bepridil reduced the amplitudes of sodium
      current in time- and concentration-dependent manners. The half-blocking time was
      about 10 min in bepridil 10 micromol.L-1, and IC50 was 2.6 (2.3-2.9) micromol.L
      1. Bepridil 10 micromol.L-1 shifted the maximal activation of sodium current from
      -50 mV to -40 mV, and the characteristic voltage of inactivation from -71 mV to 
      89 mV without changing the slope factor. CONCLUSION: Bepridil blocked voltage
      dependent sodium current of hippocampal CA1 neurons and might have therapeutic
      actions for ischemia-induced brain damage.

PMID- 11245091
TI  - Improving effects of huperzine A on abnormal lipid peroxidation and superoxide
      dismutase in aged rats.
AB  - AIM: To study the effects of huperzine A on lipid peroxidation and superoxide
      dismutase (SOD) in hippocampus, cerebral cortex, and serum of aged rats. METHODS:
      The level of lipid peroxidation was determined by thiobarbituric acid reactive
      substance method and represented as the concentration of malondialdehyde (MDA) in
      wet tissue. The activity of SOD was determined by xanthine-xanthine oxidase
      method and represented as the nitrite unit per gram protein in wet tissue.
      RESULTS: The levels of MDA and the manganese-SOD (Mn-SOD) activities in
      hippocampus, cerebral cortex, and serum of aged male rats were 2.3-2.8 times and
      1.8-2.8 times, respectively, higher than those of adult male rats. Huperzine A
      (0.05 mg/kg, ig) lowered markedly the levels of MDA and the activities of Mn-SOD
      in aged male rats following 7-14 d consecutive administrations. The MDA levels in
      hippocampus, cerebral cortex, and serum decreased 44.7-52.8% (7 d) and 52.6-54.7%
      (14 d). The Mn-SOD activities in hippocampus, cerebral cortex, and serum lowered
      25.0 -57.6% (7 d) and 56.0-74.2% (14 d). In adult rats, no marked change was
      found after 7-14 d consecutive administrations of huperzine A at a dose of 0.05
      mg/kg. CONCLUSION: Huperzine A improved the abnormal free radicals in aged rats.

PMID- 11245092
TI  - Antagonistic effects of melatonin on glutamate release and neurotoxicity in
      cerebral cortex.
AB  - AIM: To observe the effects of melatonin (Mel) on glutamate (Glu) release from
      the cortical synaptosomes in old mice and on neurotoxicity induced by KCl, Glu in
      cultured cortical cells of fetal rat and to explore the antiaging mechanism of
      Mel. METHODS: Glu release by the synaptosomes in old mouse cerebral cortex was
      detected in a spectrofluorophotometer. The neuronal viability in primary cultures
      from rat cerebral cortex was assessed using MTT stain and lactate dehydrogenase
      (LDH) efflux in the bathing medium. RESULTS: Mel inhibited the K+ (30 mmol.L-1)
      induced Glu release from synaptosomes either in calcium dependent or independent
      conditions [control (10.6 +/- 1.1), (9.2 +/- 0.7) mumol.g-1 (protein); Mel 0.1
      mumol.L-1 (6.5 +/- 0.9), (7.5 +/- 0.6) mumol.g-1 (protein), respectively, P <
      0.01 vs control group), increased MTT activity (control 0.67 +/- 0.04, 0.81 +/-
      0.03; Mel 0.1 mumol.L-1 0.715 +/- 0.023, 0.925 +/- 0.027, P < 0.01 vs control
      group] and decreased LDH efflux (control 0.400 +/- 0.016, 0.379 +/- 0.016; Mel
      0.1 mumol.L-1 0.345 +/- 0.021, 0.340 +/- 0.012, respectively, P < 0.01 vs control
      group), therefore, protected the neuronal viability against KCl and Glu-induced
      injury. CONCLUSION: The inhibitory effect of Mel on Glu release from cortical
      synaptosome and the protective effect of Mel on cortical neurons against
      neurotoxicity are its antiaging mechanisms.

PMID- 11245093
TI  - Evidence for mu opioid receptor on mouse spleen lymphocytes.
AB  - AIM: Using ohmefentanyl (Ohm), a high affinity mu opioid receptor agonist, to
      find whether mu opioid receptor exists on mouse spleen lymphocytes. METHODS: The
      proliferation rates of T-lymphocytes and B-lymphocytes were determined under
      various concentrations of Ohm with or without naloxone(Nal) in vitro. Binding
      characteristics of [3H] Ohm with mice spleen lymphocytes were studied by
      radioligand assays. RESULTS: Ohm 0.1 pmol.L(-1)-1 nmol.L-1 enhanced Con A-induced
      spleen T-cell proliferation in vitro. Nal 50 mumol.L-1, which per se enhanced the
      T-cell proliferation, blocked the enhancing effects of Ohm. However, Ohm had no
      effect on B-cell proliferation. Furthermore, a satisfactory saturable, specific,
      and reversible binding was demonstrated with Kd of (6.9 +/- 0.6) nmol.L-1, Bmax
      of (74 +/- 6) fmol/10(7) cells. The binding of [3H] Ohm was blocked by unlabeled
      Ohm or Nal. CONCLUSION: Stimulating effects of Ohm on lymphocytes were mediated
      by opioid receptors. Mouse spleen lymphocytes present mu opioid receptors.

PMID- 11245094
TI  - Effects of intra-hippocampal injection of interleukin-2 on pain threshold and
      formaldehyde-induced substance P-like immunoreactivity in periaqueductal gray and
      spinal cord.
AB  - AIM: To study the effects of intra-hippocampal injection of interleukin-2 (IL-2)
      on the substance P-like immunoreactivity (SP-LI) in both periaqueductal gray
      (PAG) and spinal cord, and on pain threshold in rats. METHODS:
      Immunohistochemistry technique was used and the paw withdrawal threshold to
      radiant heat was measured. RESULTS: Microinjection of hIL-2 480 U in hippocampus
      (Hip) increased the pain threshold (93% +/- 57%, P < 0.01). Injection of
      formaldehyde (For) in one hindpaw decreased SP-LI neuron number on both sides of
      PAG (2.9 +/- 2.8 vs 22.1 +/- 0.7, 12.3 +/- 2.0 vs 22.4 +/- 1.0, P < 0.01) and
      increased SP-LI in ipsilateral spinal cord (0.836 +/- 0.015 vs 0.59 +/- 0.09, P <
      0.01). Microinjection of hIL-2 480 U in Hip inhibited the effects of For on the
      SP-LI on both sides of the PAG (11.3 +/- 2.3 vs 2.9 +/- 2.8, 16.9 +/- 3.4 vs 12.3
      +/- 2.0, P < 0.05) and spinal cord (0.71 +/- 0.03 vs 0.836 +/- 0.015, P < 0.01).
      The combination of intraperitoneal injection of corticotropin and intra
      hippocampal injection of IL-2 increased the number of SP-LI neurons in PAG
      furtherly as compared with IL-2 240 U alone (13.6 +/- 3.6 vs 7.6 +/- 4.3, P <
      0.05). CONCLUSION: The analgesic effects of intra-hippocampal injection of IL-2
      are mediated, possibly, via the increased of SP in PAG and the decrease of SP in
      the spinal cord. There is a synergetic relation between IL-2 and corticotropin.

PMID- 11245095
TI  - Characteristics of impaired endothelium-dependent relaxation of rat aorta after
      streptozotocin-induced diabetes.
AB  - AIM: To study whether impaired endothelium-dependent relaxation (EDR) in early
      diabetic mellitus in response to different receptor-mediated and nonreceptor
      mediated vasodilators ran parallel and its possible mechanism. METHODS: Isometric
      tension recording in aortic rings from streptozotocin (Str)-induced diabetic and
      age-matched nondiabetic rats. RESULTS: EDR induced by receptor agonist
      acetylcholine (ACh), histamine (His) or bradykinin (BK) were all significantly
      reduced in diabetic rings compared with control rings, whereas nonreceptor
      agonist calcimycin-induced EDR was well reserved in diabetic rings [IC50 control:
      (0.13 +/- 0.07) mumol.L-1 diabetic: (0.14 +/- 0.06) mumol.L-1, P > 0.05, n = 7].
      Cyclopiazonic acid (CPA) which also is a nonreceptor mediated endothelium
      dependent vasorelaxant and cells' capacitative Ca2+ entry stimulant, failed to
      trigger EDR in diabetic rings. Pretreatment with N omega-nitro-L-arginine
      methylester (L-NAME, 0.3 mmol.L-1) not only abolished all of the EDR elicited by
      above mentioned vasodilators in either of diabetic or control rings, but also
      leveled responses triggered by each of the agonists between diabetic and control
      rings. Upon the maximal EDR induced by ACh (1 mol.L-1) or CPA (3 mumol.L-1) in
      phenylephrine (1 mumol.L-1) precontracted rings, calcimycin (1 mumol.L-1) further
      relaxed diabetic rings, but contracted control preparations. When endothelium was
      denuded, relaxation evoked by sodium nitroprusside and contractions triggered by
      CPA or His were all identical between diabetic and control rings. CONCLUSION:
      Receptor agonists but not nonreceptor agonists-induced EDR are commonly impaired
      in 4-wk Str-induced diabetic rat aorta, and this defective effect is attributable
      to the low formation of EDRF/NO which is related to impaired capacitative Ca2+
      entry pathway in endothelium.

PMID- 11245096
TI  - Inhibition of platelet aggregation by bovine endocardial apyrase.
AB  - AIM: To study the anti-aggregatory effect of bovine endocardial endothelial cell
      (EEC)-associated apyrase. METHODS: Cultured bovine EEC was used. Adenosine
      diphosphate (ADP) was analyzed by reversed phase HPLC, and rabbit platelet
      aggregation was measured turbimetrically. RESULTS: Incubation of EEC with ADP 500
      mumol.L-1 resulted in a progressive decrease in ADP concentration, which was
      paralleled by the decrease in platelet aggregating potential of the unmetabolized
      ADP. In the presence of aspirin (Asp 1 mmol.L-1)-treated EEC 1 x 10(9) cells.L-1,
      the aggregation of Asp (1 mmol.L-1) and methylene blue (10 mumol.L-1)-treated
      platelets in response to thrombin 500 U.L-1 and platelet activating factor (PAF 1
      nmol.L-1) was markedly inhibited and was reversible, which was very similar to
      that in apyrase-treated platelets. The supernatants of EEC had no effect on
      platelet aggregation. EEC inhibited ADP (5 mumol.L-1)-induced platelet
      aggregation, but failed to inhibit adenosine 5'-O-(2-thiodiphosphate) (ADP-beta
      S, an unmetabolizable structural analog of ADP, 15 mumol.L-1)-induced platelet
      aggregation. CONCLUSION: ADP hydrolysis by EEC-associated apyrase is a major anti
      thrombotic mechanism of bovine EEC.

PMID- 11245097
TI  - Effects of fluvastatin on structure and function of resistant vessels in
      spontaneously hypertensive rats.
AB  - AIM: To evaluate the effects of fluvastatin, a hydroxymethylglutaryl-CoA (HMG
      CoA) reductase inhibitor, on the alterations of structure and function of
      resistant vessels in spontaneously hypertensive rats (SHR). METHODS: Eight-week
      old male SHR were given fluvastatin 20 mg.kg-1.d-1 by gavage. Rats were
      decapitated at 16 wk. Wall-to-lumen area ratios (W/L) of thoracic aorta and
      mesenteric arteries (3rd grade branch) were assessed by morphometric assay. The
      effects of fluvastatin on vascular reactivity to sodium nitroprusside (SNP) and
      norepinephrine (NE), were studied with rings of thoracic aorta and mesenteric
      arteries isolated from rats. RESULTS: After 8 wk of treatment, histological
      examination showed that the wall-to-lumen area ratio was lower in SHRflu than
      that in SHR (0.44 +/- 0.09 vs 0.79 +/- 0.09, P < 0.05). EC50 of vasodilation
      response was much lower in SHRflu than that in SHR [(4.9 vs 190) pmol.L-1, P <
      0.05], while EC50 of mesenteric artery rings from SHRflu was somewhat lower than
      that of SHR [(0.02 vs 0.04) nmol.L-1, P > 0.05]. In both aortic and mesenteric
      artery rings, EC50 of vasoconstriction in response to NE from SHRflu was higher
      than that of SHR [thoracic aorta: (0.20 vs 0.02) nmol.L-1, P < 0.05; mesentric
      arteries: (1.46 vs 0.72) nmol.L-1, P < 0.05]. CONCLUSION: Short-term treatment
      with fluvastatin ameliorated the vasomotoricity of resistant vessels, enhanced
      the sensitivity to vasodilator and depressed the sensitivity to vasoconstrictor;
      fluvastatin also attenuated the resistant vascular hypertrophy during the
      development of hypertension in SHR.

PMID- 11245098
TI  - Ca2+ sensitivity of contractile system and Ca2+ release from sarcoplasmic
      reticulum in skinned myocardium from rats with pressure overload LV hypertrophy
      and heart failure.
AB  - AIM: To explore the possible subcellular mechanisms underlying the decreased
      contractility of myocardium in left ventricle failured hearts caused by pressure
      overload. METHODS: Left ventricle pressure overload hypertrophy (LVH) and
      congestive heart failure (CHF) models were created in rats by ascending aortic
      banding. Left ventricle trabeculae skinned fibers were prepared by treatment with
      saponin 500 or 50 mg.L-1. Relative Ca(2+)-activated tensions (T6.0% and T5.6%) of
      saponin (500 mg.L-1)-skinned fibers were taken as the indices of Ca2+ sensitivity
      of contractile protein, caffeine-induced contracture of saponin 50 mg.L-1-skinned
      fibers was an index of Ca2+ release from sarcoplasmic reticulum (SR). RESULTS: 1)
      There was no significant difference in relative Ca2+ activated tensions among
      CHF, LVH, and Sham-operated group in basic situation (P > 0.05). After treatment
      with caffeine 10 mmol.L-1, the increase in value of delta T% were significantly
      higher in LVH and CHF compared with that in Sham-operated control (P < 0.01). 2)
      The amplitudes of caffeine (5 and 10 mmol.L-1)-induced contracture were (0.66 +/-
      0.14) and (1.20 +/- 0.27) g/mm2 in control group, 19.8% and 25.8% lower in LVH (P
      < 0.05), 78.8% and 80.9% much more lower in CHF (P < 0.01). CONCLUSION: Decreased
      SR Ca2+ release was the main factor responsible for depressed contractility in
      failured myocardium while the Ca2+ sensitivity of contractile protein might not
      be involved.

PMID- 11245099
TI  - Thoracic organ transplantation in Japan: still in the beginning stages.

PMID- 11245100
TI  - Avedis Donabedian, 7 January 1919-9 November 2000.

PMID- 11245101
TI  - BOOP associated with nitrofurantoin.

PMID- 11245102
TI  - Outcome measures in asthma.

PMID- 11245103
TI  - Capsaicin responsiveness in asthma and COPD.

PMID- 11245104
TI  - [Recommendations for accreditation in internal medicine].

PMID- 11245105
TI  - [Comments on "Recommendations on accreditation in internal medicine" by the
      Slovak Society of Internal Medicine].

PMID- 11245106
TI  - [Development and perspectives of internal medicine in Slovakia].

PMID- 11245107
TI  - Tc-99m DTPA renography in patients with collagen disease.
AB  - PURPOSE: This study evaluated the use of Tc-99m DTPA renography in patients with
      collagen disease. MATERIALS AND METHODS: Tc-99m DTPA renal scintigraphy was
      performed in 28 patients with clinically diagnosed collagen disease. Twenty-two
      other patients who underwent renal scintigraphy and were subsequently shown to
      have no kidney abnormalities served as the control group. RESULTS: One quarter of
      the patients with collagen disease had abnormal findings of renography, despite
      the absence of abnormal laboratory data. Renograms were 100% sensitive for the
      detection of renal disease in patients with collagen disease, and their
      specificity was 53% when serum blood urea nitrogen, serum creatinine
      concentration, and proteinuria were the only measures of renal impairment
      considered. The glomerular filtration rate was not significantly different
      between the groups, but the bilateral time to peak was significantly greater in
      the patients with collagen disease. Hydronephrosis was present in 7% of patients
      with collagen disease. CONCLUSION: Renography is useful for detecting early
      changes of renal involvement when the clinical state of collagen disease is
      evaluated.

PMID- 11245108
TI  - Incidental focal thyroid uptake on FDG positron emission tomographic scans may
      represent a second primary tumor.
AB  - PURPOSE: This article discusses the value of incidental thyroid uptake of
      fluorodeoxyglucose (FDG) on whole-body positron emission tomography (PET) scans
      performed in patients with cancer. This issue has been reported diversely in the
      literature. MATERIALS AND METHODS: Whole-body PET scans of four patients with
      cancer (two of them women; age, 49 to 78 years) in whom focal thyroid uptake was
      visualized and subsequently correlated with thyroid carcinoma based on cytologic
      or histopathologic data were reviewed. The clinical outcomes of these patients
      were analyzed retrospectively. Maximum and average standardized uptake values
      (SUVs) of thyroid accumulation were recalculated in all patients. RESULTS: Two of
      the four patients referred for FDG PET scans had lung adenocarcinomas, one had
      prostate carcinoma, and one had an unknown primary tumor. Focal thyroid uptake
      was visualized, with maximum and average SUVs ranging from 3.7 and 2.3 to 53 and
      34, respectively. These findings were correlated with cytologic (two patients) or
      histopathologic data (two patients) that indicated thyroid carcinoma. In two
      patients, their treatment was changed and total thyroidectomy was performed; in
      one of them the SUVs of the focal thyroid accumulation (maximum and average
      values of 7.9 and 4.8, respectively) were less than the cutoff values for thyroid
      cancer noted in the literature. The clinical condition of the other two patients
      did not permit additional investigation or treatment for thyroid carcinoma.
      CONCLUSION: Increased focal thyroid uptake on whole-body FDG PET scans should not
      be overlooked, even when it is not marked, and should prompt further
      investigation to rule out cancer.

PMID- 11245109
TI  - False-positive I-131 accumulation in a liver cyst in a patient with thyroid
      carcinoma.
AB  - Iodine-131 uptake was seen in the right upper abdominal quadrant of a patient
      with postoperative differentiated thyroid cancer that corresponded with a large
      liver cyst.

PMID- 11245110
TI  - Quantitative analysis of regional wall motion and thickening by quantitative
      gated SPECT: comparison with visual analysis.
AB  - PURPOSE: Electrocardiograph-gated myocardial SPECT permits a quantitative
      assessment of global and regional functions by quantitative gated SPECT software.
      To validate quantitative indexes of wall motion and wall thickening, the authors
      compared these indexes with visual scores. MATERIALS AND METHODS: Gated
      myocardial SPECT was performed 60 minutes after the administration of Tc-99m
      sestamibi at rest in 42 patients with coronary artery disease. Regional wall
      motion (measured in millimeters and wall thickening (expressed as a percentage)
      were calculated by quantitative gated SPECT software in nine left ventricular
      myocardial segments and the results were compared with the five-point visual
      score interpretations of cinematic display. RESULTS: A high correlation of wall
      motion was observed between the quantitative and visual analyses (r = 0.810; P <
      0.001). In addition, a high but somewhat less significant correlation of wall
      thickening was observed between the quantitative and visual analyses (r = 0.606;
      P < 0.001). CONCLUSIONS: In conclusion, regional wall motion and wall thickening
      can be evaluated quantitatively by electrocardiograph-gated myocardial SPECT and
      quantitative gated SPECT software. This will be useful for functional assessments
      made with various interventions.

PMID- 11245111
TI  - Tc-99m Infecton scan in possible pelvic inflammatory disease.
AB  - Tc-99m Infecton imaging was used to examine patients thought to have pelvic
      inflammatory disease (PID) based on clinical and sonographic findings. Twenty-one
      patients with PID had Tc-99m Infecton scans. Eleven patients underwent a second
      radionuclide scan after 1 month of antibiotic treatment. The diagnosis of PID was
      confirmed by laparoscopy in one patient who was later found to have a tubercular
      infection. In the remaining patients, the diagnosis was based on uterine
      tenderness, fever and lower abdominal pain that responded to antibiotics, and
      ultrasound findings. These patients had infection of the uterus, fallopian tubes,
      the cul-de-sac, or all of these. The Tc-99m Infecton scan appears to be useful in
      the diagnosis of possible PID and is recommended after a complete course of
      antibiotics for monitoring treatment response.

PMID- 11245112
TI  - Comparison of Tc-99m sestamibi and TI-201 uptake in multiple myeloma.
AB  - The authors report abnormal Tc-99m sestamibi (MIBI) and TI-201 uptake in a 62
      year-old patient with histologically and biochemically proved myeloma. TI-201
      imaging was undertaken for tumor evaluation, and 3 days later a Tc-99m MIBI study
      showed diffuse and focal marrow uptake with focal skull lesions, whereas TI-201
      did not show skull lesions. After treatment, follow-up Tc-99m MIBI whole-body
      imaging was performed and the marrow uptake was decreased.

PMID- 11245113
TI  - Asymptomatic large main pulmonary artery thromboembolism with a low-probability
      ventilation-perfusion lung scan.
AB  - The incidence of the interpretation of low-probability lung scans in asymptomatic
      patients with large central pulmonary embolisms and the prognostic implication of
      the ventilation-perfusion scan appearance in this clinical setting is not
      documented.

PMID- 11245114
TI  - Utility of Tc-99m GSA whole-body scintigraphy in detecting bone metastases from
      hepatocellular carcinoma.
AB  - Recent advances in the treatment of hepatocellular carcinoma (HCC) have prolonged
      patient survival. However, the number of patients with bone metastases identified
      during follow-up examinations has increased. Tc-99m Sn-N-pyridoxy-5
      methyltryptophan (Tc-99m PMT) has been reported to accumulate at a high rate in
      HCC lesions and bone metastases. In the patient described here, whole-body
      scintigraphy showed accumulation of DTPA galactosyl human serum albumin (Tc-99m
      GSA) and Tc-99m PMT in bone metastases from HCC. The authors suggest that
      asialoglycoprotein receptors may be present in bone metastases from well
      differentiated HCC. Tc-99m GSA whole-body imaging can be used to detect bone
      metastases from HCC and to evaluate hepatic reserve.

PMID- 11245115
TI  - Microvascularized fibular graft for mandibular reconstruction: detection of
      viability by bone scintigraphy and SPECT.
AB  - Bone allografts are often used in reconstructive mandibular surgery, generally
      after extensive oncologic resection, post-traumatic pseudoarthrosis, or
      osteomyelitis. Vascularized fibular bone grafts have advantages compared with
      other bone grafts in the restoration of the contour and function of defective
      mandibles. Bone scintigraphy is often used to assess bone revascularization,
      because positive uptake of Tc-99m hydroxy methylene diphosphonate (HDP) reflects
      patent anastomoses and viability of the grafted bone. Mandibular reconstruction
      with a free fibular flap was performed in 11 patients. Bone scintigraphy and
      SPECT were applied in the follow-up of eight patients. The grafts were assessed
      semi-quantitatively using a six-grade scoring system based on a comparison of
      tracer uptake in the graft and in the calvarium. Complications were observed in
      one graft. Planar scintigrams showed a tracer uptake greater than grade 5 in
      grafts with an uncomplicated course. SPECT was performed in addition to planar
      imaging in two patients who had greater graft uptake. A lack of tracer uptake was
      observed in the failed graft. Bone scintigraphy performed within the first week
      after the mandibular reconstruction is a useful tool to monitor the viability and
      early complications of microvascularized fibular grafts and plays an important
      role in the decision-making process during repeated surgical exploration. SPECT
      is more sensitive than planar imaging for assessing graft viability.

PMID- 11245116
TI  - Pelvic metastases from pancreatic carcinoma: a pattern observed on bone scan.
AB  - Metastases to the bony pelvis is an unusual pattern of the spread of primary
      pancreatic tumors. The authors report the presence of metastatic disease in the
      bony pelvis observed on bone scans in several patients who had been treated
      recently for pancreatic carcinoma. When bone scans that show metastatic disease
      in the pelvis are evaluated in patients with unknown primaries, the diagnosis of
      pancreatic carcinoma should be considered.

PMID- 11245117
TI  - Therapy monitoring in aspergillosis using F-18 FDG positron emission tomography.

PMID- 11245118
TI  - Chronic osteomyelitis: clarification of nuclear medicine findings by fusion
      scans.

PMID- 11245119
TI  - Radionuclide imaging in bilateral os trigonum syndrome in a young athlete.

PMID- 11245120
TI  - Scintigraphic demonstration of the origin of postoperative bile leak.

PMID- 11245121
TI  - Postfemoral venipuncture hematoma: a potential false-positive gastrointestinal
      bleeding scan.

PMID- 11245122
TI  - FDG uptake in chronic superior vena cava thrombus on positron emission
      tomographic imaging.

PMID- 11245123
TI  - Three different areas of decreased hepatic radioactivity secondary to a hilar
      mass.

PMID- 11245124
TI  - Paget disease and osteosarcoma of the calcaneus.

PMID- 11245125
TI  - Ga-67-avid non-Hodgkin's lymphoma arising from chronic nontuberculous pyothorax.

PMID- 11245126
TI  - Metastatic peritoneal seeding patterns demonstrated by FDG positron emission
      tomographic imaging.

PMID- 11245127
TI  - Positive In-111 pentetreotide scintigraphy: pulmonary hamartoma.

PMID- 11245128
TI  - A case of hepatocellular carcinoma mimicking cavernous hemangioma on Tc-99m RBC
      liver SPECT.

PMID- 11245129
TI  - Abdominal uptake of I-131 revealing a renal cyst.

PMID- 11245130
TI  - Tc-99m DMSA and Tc-99m DTPA imaging in the diagnosis of crossed renal ectopia.

PMID- 11245131
TI  - Demonstration of uterus didelphys on renal transplant scan in a patient with
      multiple cloacal anomalies.

PMID- 11245132
TI  - Two patterns of blood pooling in giant hemangiomas on Tc-99m RBC scintigraphy.

PMID- 11245133
TI  - Multiple bone and joint involvement in a boy with Staphylococcal sepsis.

PMID- 11245134
TI  - Renal cell carcinoma detected by Tc-99m MDP bone imaging.

PMID- 11245135
TI  - Osteonecrosis in Behcet's disease seen on bone scintigraphy.

PMID- 11245136
TI  - Neuroma in phantom limb syndrome: blood-pool and magnetic resonance imaging
      findings.

PMID- 11245137
TI  - False-positive results of an iodine-131 whole-body scan caused by an ectopic
      kidney.

PMID- 11245138
TI  - Current readings in nuclear medicine.

PMID- 11245139
TI  - The parotid gland: an unusual site of metastasis from carcinoma of breast.

PMID- 11245140
TI  - Cardiac toxicity secondary to long term treatment with chloroquine.

PMID- 11245141
TI  - A pilot study of the salivary scintigraphy diagnostic performance in a Spanish
      population with Sjogren's syndrome diagnosed by the  European criteria.

PMID- 11245142
TI  - Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) as
      recurrence of aborted PMR.

PMID- 11245143
TI  - antiphospholipid antibodies and RA: presence of beta2GP1 independent aCL.

PMID- 11245144
TI  - Ethical aspects of new medicines targeted at treatment of RA.

PMID- 11245145
TI  - Montelukast and Churg-Strauss syndrome.

PMID- 11245146
TI  - Montelukast and Churg-Strauss syndrome.

PMID- 11245147
TI  - Montelukast sodium in cystic fibrosis.

PMID- 11245148
TI  - Declining incidence of episodes of asthma.

PMID- 11245149
TI  - Declining incidence of episodes of asthma.

PMID- 11245150
TI  - Declining incidence of episodes of asthma.

PMID- 11245151
TI  - Percutaneous sacral third nerve root neurostimulation improves symptoms and
      normalizes urinary HB-EGF levels and antiproliferative activity in patients with
      interstitial cystitis.

PMID- 11245152
TI  - CHW (Catholic Healthcare West) faces Medicare fraud charges. Feds allege
      Sacramento, Calif., hospitals filed false cost reports.

PMID- 11245154
TI  - Flouting the law. New York taking steps to counter hospitals' underreporting of
      errors.

PMID- 11245153
TI  - Hospital's ex-CEO indicted. Another top administrator caught in legal mire faces
      seven counts of theft.

PMID- 11245155
TI  - The burden of post-prandial hyperglycemia and its implications.

PMID- 11245156
TI  - [Portal hypertension treatment: the road had now a new and good rebuilding but
      still long and hard].

PMID- 11245157
TI  - [Evaluation of rapid urease test stored in refrigerator].
AB  - The rapid urease test is an accurate and cheap method, which results are readily
      available, and broadly used for routine Helicobacter pylori infection diagnosis.
      AIM: The evaluation of rapid urease test stored in refrigerator at 4 degrees C
      (SRUT) compared to regular rapid urease test. PATIENTS AND METHOD: Endoscopic
      biopsies were obtained from gastric antrum in 104 consecutive patients. Diagnosis
      of Helicobacter pylori infection was accomplished by rapid urease test, histology
      and rapid urease test stored (kept in refrigerator by a period ranging from 1 to
      8 days). RESULTS: Infection was considered present if both rapid urease test and
      histology were positive. Helicobacter pylori was present in 45/104 patients
      (42%). Rapid urease test stored had specificity comparable to rapid urease test
      (93%), with sensitivity of 88%. CONCLUSION: We concluded that rapid urease test
      can be stored in refrigerator for up to 1 week, without loss of clinical
      applicability, and that can make the test even easier to use for routine
      Helicobacter pylori tests in a busy endoscopy unit.

PMID- 11245159
TI  - Recent Developments and Future Directions with HER-2 in Breast Cancer and Other
      Tumor Types. Proceedings of a roundtable. August 11-14, 1999. Olympic Valley,
      California, USA.

PMID- 11245158
TI  - [Surgical procedures in selected proctological patients with local anesthesia.
      Study of 150 cases].
AB  - Experience in the treatment of 150 patients with anorectal disorders and
      disorders of the sacrococcygeal region who were operated on with local anesthesia
      at the University Hospital, ABC Medical School, Sao Bernardo do Campo, SP,
      Brazil, from March 1995 to March 1998. The anesthesia technique, the operations
      carried out and the tolerance to the procedure are reported. Intraoperative
      morbidity was 10.6% (16 patients), and postoperative morbidity was 6% (nine
      patients). The age of patients was between 15 and 92 years old, with mean age 42
      years old; 58% of patients were male and 42% female. Surgical mean time was 45
      minutes and the patients remained in the hospital for a mean time of 8 hours. All
      of patients was instructed about the anesthesia technique, their advantages and
      disadvantages, and only with their permit the surgery was programmed.
      Hospitalization was required in five patients (3.3%). The anesthesia technique
      employed was the same for all patients. Upon survey, 96.7% of the patients stated
      they did not feel pain during the surgery and that they would go through the
      procedure again. The authors conclude the surgical treatment of anorectal
      disorders and disorders of the sacrococcygeal region with local anesthesia is
      viable and safe, and in addition, is well accepted by the patients.

PMID- 11245160
TI  - 1Q[3a] Should disciplinary action against doctors be posted?

PMID- 11245161
TI  - Valid protest or ego trip?

PMID- 11245162
TI  - Miracles.

PMID- 11245163
TI  - Medication safety issue brief. Using automation to reduce errors. Part 2.
AB  - The medication-use system in hospitals is inherently complex. There can be more
      than 100 steps from the time a prescription is written to the time a patient
      receives the medication. Technology has the potential to reduce medication errors
      by reducing complexity, avoiding over-reliance on memory, simplifying key
      processes, and, if designed and implemented properly, increasing efficiency. It
      can also be a cost-effective tool for improving quality. This briefing examines
      issues in selection and implementation automation.

PMID- 11245164
TI  - Physicians and the Internet. Taking the pulse.

PMID- 11245165
TI  - Close to home. Your own staff can solve many problems with your hospital's
      medication system.

PMID- 11245166
TI  - Host sequences in Plasmodium falciparum and Plasmodium vivax genomic DNA:
      horizontal transfer or contamination artifact?

PMID- 11245167
TI  - Host-like molecules in human malarial parasites.

PMID- 11245169
TI  - vCJD: broad U.S. response required.

PMID- 11245168
TI  - Comments on the recently reported low biological effectiveness of ultrasoft X
      rays.

PMID- 11245170
TI  - Rat genome spurs an unusual partnership.

PMID- 11245172
TI  - Archaeology.  Heavy damage feared after Taliban decree.

PMID- 11245171
TI  - Malaria research.  Sequencing set for dreaded mosquito.

PMID- 11245174
TI  - German science.  New money to lure talent from abroad.

PMID- 11245173
TI  - Astrobiology.  Are Martian 'pearl chains' signs of life?

PMID- 11245175
TI  - Scientific misconduct.  Fallout from German fraud case continues.

PMID- 11245176
TI  - Quantum chromodynamics.  Quark quirk triggers nuclear shrinkage.

PMID- 11245178
TI  - China.  Academician to lead science ministry.

PMID- 11245177
TI  - Philanthropy.    Russian billionaires launch science fund.

PMID- 11245179
TI  - Behavioral genetics.  Study suggests pitch perception is inherited.

PMID- 11245180
TI  - AIDS vaccines.  Long-lasting immunity conferred in monkeys.

PMID- 11245181
TI  - Prion research:  Getting yeast prions to bridge the species gap.

PMID- 11245183
TI  - Policy:  Budget could send space science off in new directions at NASA.

PMID- 11245182
TI  - Policy.  Science lobbyists aim for better balanced budget.

PMID- 11245184
TI  - Botany.  Patience yields secrets of seed longevity.

PMID- 11245185
TI  - Engineering education.  Olin puts up $500 million for 'no-excuses' college.

PMID- 11245186
TI  - Engineering education.  Academic excellence is just a start for prospective
      students at Olin.

PMID- 11245187
TI  - Portugal.  Money and charisma help the science tide come in.

PMID- 11245188
TI  - Mir space station.  Fiery demise spells end of longest research run.

PMID- 11245189
TI  - Choosing the sources of sustainable energy.

PMID- 11245190
TI  - Longisquama fossil and feather morphology.

PMID- 11245191
TI  - Longisquama fossil and feather morphology.

PMID- 11245192
TI  - Bird song in his heart.

PMID- 11245194
TI  - Public health.   Proliferation of National Institutes of Health.

PMID- 11245195
TI  - Planetary science.    Erosion by the solar wind.

PMID- 11245197
TI  - Laser physics.   Toward attosecond pulses.

PMID- 11245196
TI  - Developmental neuroscience.   Moving on.

PMID- 11245198
TI  - Paleontology and evolution.   The origins of modern corals.

PMID- 11245199
TI  - Signaling antibiotic resistance in staphylococci.

PMID- 11245200
TI  - Molecular biology.   RNP remodeling with DExH/D boxes.

PMID- 11245202
TI  - A personal account of the role of peptide research in drug discovery: the case of
      hepatitis C.
AB  - Although peptides themselves are not usually the end products of a drug discovery
      effort, peptide research often plays a key role in many aspects of this process.
      This will be illustrated by reviewing the experience of peptide research carried
      out at IRBM in the course of our study of hepatitis C virus (HCV). The target of
      our work is the NS3/4A protease, which is essential for maturation of the viral
      polyprotein. After a thorough examination of its substrate specificity we fine
      tuned several substrate-derived peptides for enzymology studies, high-throughput
      screening and as fluorescent probes for secondary binding assays. In the course
      of these studies we made the key observation: that the protease is inhibited by
      its own cleavage products. Single analog and combinatorial optimization then
      derived potent peptide inhibitors. The crucial role of the NS4A cofactor was also
      addressed. NS4A is a small transmembrane protein, whose central domain is the
      minimal region sufficient for enzyme activation. Structural studies were
      performed with a peptide corresponding to the minimal activation domain, with a
      series of product inhibitors and with both. We found that NS3/4A is an induced
      fit enzyme, requiring both the cofactor and the substrate to acquire its
      bioactive conformation; this explained some puzzling results of 'serine-trap'
      type inhibitors. A more complete study on NS3 activation, however, requires the
      availability of the full-length NS4A protein. This was prepared by native
      chemical ligation, after sequence engineering to enhance its solubility;
      structural studies are in progress. Current work is focused on the P' region of
      the substrate, which, at variance with the P region, is not used for ground state
      binding to the enzyme and might give rise to inhibitors showing novel
      interactions with the enzyme.

PMID- 11245201
TI  - Crystal-state conformation of Calpha,alpha-dialkylated peptides containing chiral
      beta-homo-residues.
AB  - Secondary structure formation and stability are essential features in the
      knowledge of complex folding topology of biomolecules. To better understand the
      relationships between preferred conformations and functional properties of beta
      homo-amino acids, the synthesis and conformational characterization by X-ray
      diffraction analysis of peptides containing conformationally constrained
      Calpha,alpha-dialkylated amino acid residues, such as alpha-aminoisobutyric acid
      or 1-aminocyclohexane-1-carboxylic acid and a single beta-homoamino acid,
      differently displaced along the peptide sequence have been carried out. The
      peptides investigated are: Boc-betaHLeu-(Ac6c)2-OMe, Boc-Ac6c-betaHLeu-(Ac6c)2
      OMe and Boc-betaHVal-(Aib)5-OtBu, together with the C-protected beta-homo-residue
      HCl.H-betaHVal-OMe. The results indicate that the insertion of a betaH-residue at
      position 1 or 2 of peptides containing strong helix-inducing, bulky Calpha,alpha
      disubstituted amino acid residues does not induce any specific conformational
      preferences. In the crystal state, most of the NH groups of beta-homo residues of
      tri- and tetrapeptides are not involved in intramolecular hydrogen bonds, thus
      failing to achieve helical structures similar to those of peptides exclusively
      constituted of Calpha,alpha-disubstituted amino acid residues. However, by
      repeating the structural motifs observed in the molecules investigated, a beta
      pleated sheet secondary structure, and a new helical structure, named (14/15)
      helix, were generated, corresponding to calculated minimum-energy conformations.
      Our findings, as well as literature data, strongly indicate that conformations of
      betaH-residues, with the micro torsion angle equal to -60 degrees, are very
      unlikely.

PMID- 11245203
TI  - Two short peptides including segments of subunit A of Escherichia coli DNA gyrase
      as potential probes to evaluate the antibacterial activity of quinolones.
AB  - Quinolones constitute a family of compounds with a potent antibiotic activity.
      The enzyme DNA gyrase, responsible for the replication and transcription
      processes in DNA of bacteria, is involved in the mechanism of action of these
      drugs. In this sense, it is believed that quinolones stabilize the so-called
      'cleavable complex' formed by DNA and gyrase, but the whole process is still far
      from being understood at the molecular level. This information is crucial in
      order to design new biological active products. As an approach to the problem, we
      have designed and synthesized low molecular weight peptide mimics of DNA gyrase.
      These peptides correspond to sequences of the subunit A of the enzyme from
      Escherichia coli, that include the quinolone resistance-determining region
      (positions 75-92) and a segment containing the catalytic Tyr-122 (positions 116
      130). The peptide mimic of the non-mutated enzyme binds to ciprofloxin (CFX) only
      when DNA and Mg2+ were present (Kd = 1.6 x 10(-6) M), a result previously found
      with DNA gyrase. On the other hand, binding was reduced when mutations of Ser-83
      to Leu-83 and Asp-87 to Asn-87 were introduced, a double change previously found
      in the subunit A of DNA gyrase from several CFX-resistant clinical isolates of E.
      coli. These results suggest that synthetic peptides designed in a similar way to
      that described here can be used as mimics of gyrases (topoisomerases) in order to
      study the binding of the quinolone to the enzyme-DNA complex as well as the
      mechanism of action of these antibiotics.

PMID- 11245204
TI  - Conformation and ion channel properties of a five-helix Bundle protein.
AB  - The primary amphipathic peptide Ac-Met-Gly-Leu-Gly-Leu-Trp-Leu-Leu-Val-Leu10-Ala
      Ala-Ala-Leu-Gln-Gly-Ala-Lys-Lys-Lys20-Arg-Lys-Val-NH-CH2-CH2-SH called SPM was
      able to induce formation of ion channels into planar lipid bilayers with main
      conductance values of 75 and 950 pS in 1 M KCl. The 75 pS value can be attributed
      to an aggregate composed of five monomers since the corresponding five-unit
      bundle (5-SPM) also presented a 70 pS channels under the same conditions. The
      upper 950 pS level would be generated by a hexameric aggregate. Ion channels
      induced by both SPM and its pentameric bundle are slightly cation selective but
      not voltage-dependent. The structural studies showed that the SPM and 5-SPM
      possess mainly an alpha-helical structure (approximately 40%) and are strongly
      embedded in the bilayer. This behaviour and the strong hydrophobic interactions
      occurring between helices in the bundle induce a strong stabilization of 5-SPM in
      the bilayer and would be responsible for the stepwise current fluctuations
      observed during the incorporation of 5-SPM into the membrane.

PMID- 11245205
TI  - Expression, refolding and indirect immobilization of horseradish peroxidase (HRP)
      to cellulose via a phage-selected peptide and cellulose-binding domain (CBD).
AB  - We examined the potential immobilization of horseradish peroxidase (HRP) to
      cellulose with cellulose-binding domain (CBD) as a mediator, using a ligand
      selected from a phage-displayed random peptide library. A 15-mer random peptide
      library was panned on cellulose-coated plates covered with CBD in order to find a
      peptide that binds to CBD in its bound form. The sequence I/LHS, which was found
      to be an efficient binder of CBD, was fused to a synthetic gene of HRP as an
      affinity tag. The tagged enzyme (tHRP) was then immobilized on microcrystalline
      cellulose coated with CBD, thereby demonstrating the indirect immobilization of a
      protein to cellulose via three amino acids selected by phage display library and
      CBD.

PMID- 11245206
TI  - Synthesis of of beta-amyloid precursor peptide and presenilin segments.
AB  - It seems likely that the beta-amyloid precursor protein (APP) and the presenilins
      (PS-1/2) play important roles in the development of Alzheimer's disease (AD).
      Attempts to mimic the biochemical actions of these proteins are often made by the
      application of fragments of these proteins. However, the synthesis of these
      segments by conventional methods of peptide synthesis is problematic. We have
      synthesized several C-terminal fragments of APP and PS-1/2 by solid-phase
      synthesis through combination of automatic and manual methods of synthesis. This
      permits solution of the 'difficult sequences' in the solid-phase synthesis of
      these peptides. Some details of the syntheses of nine segments are presented in
      this paper.

PMID- 11245207
TI  - Mitochondrial myopathies and the role of the pathologist in the molecular era.
AB  - Mitochondrial encephalomyopathies are under increasing consideration in the
      differential diagnosis of diverse metabolic diseases from infancy to late
      adulthood. This is to be expected considering the vital importance of
      mitochondria to cellular respiration in all eukaryotes. the vulnerability of the
      mitochondrial genome to injury, and the expanding appreciation of the role of
      mitochondria as a common denominator in cell death in ischemia/anoxia, sepsis,
      and neurodegenerative diseases. Primary disease of the mitochondrial respiratory
      chain is estimated to occur with an incidence of between 6 and 16/100,000
      individuals. Virtually all tissues have been shown to be involved in diverse
      mitochondriopathies, but none is more appropriate for diagnosis in most cases
      than skeletal muscle. The conventional histological and ultrastructural diagnosis
      of mitochondrial disease in muscle has been increasingly supplanted by the
      biochemical assessment of respiratory chain enzyme deficiencies and definitive
      genetic diagnosis. The use of such techniques has afforded a greater
      understanding for the relative lack of specificity of both light and electron
      microscopic observations. A review of the current situation by placing muscle
      pathology in the context of biochemical and genetic diagnosis serves as a
      paradigm for the role of the pathologist in the molecular era.

PMID- 11245208
TI  - Medullary serotonergic network deficiency in the sudden infant death syndrome:
      review of a 15-year study of a single dataset.
AB  - The sudden infant death syndrome (SIDS) is the leading cause of postneonatal
      infant mortality in the United States today, despite a dramatic 38% decrease in
      incidence due to a national risk reduction campaign advocating the supine sleep
      position. Our research in SIDS brainstems, beginning in 1985 and involving a
      single, large dataset, has become increasingly focused upon a specific
      neurotransmitter (serotonin) and specific territories (ventral medulla and
      regions of the medullary reticular formation that contain secrotonergic neurons).
      Based on this research, we propose that SIDS, or a subset of SIDS, is due to a
      developmental abnormality in a medullary network composed of (at least in part)
      rhombic lip-derived, serotonergic neurons, including in the caudal raphe and
      arcuate nucleus (putative human homologue of the cat respiratory chemosensitive
      fields); and this abnormality results in a failure of protective responses to
      life-threatening stressors (e.g. asphyxia, hypoxia, hypercapnia) during sleep as
      the infant passes through a critical period in homeostatic control. We call this
      the medullary serotonergic network deficiency hypothesis. We review the triple
      risk model for SIDS, the development of the dataset using tissue autoradiography
      for analyzing neurotransmitter receptor binding; age-dependent baseline
      neurochemical findings in the human brainstem during early life; the evidence for
      serotonergic, rhombic lip, and ventral medullary deficits in at least some SIDS
      victim; possible mechanisms of sudden infant death related to these deficits; and
      potential causes of the deficits in the medullary serotonergic network in SIDS
      victims. We conclude with a summary of future directions in SIDS brainstem
      research.

PMID- 11245209
TI  - Oligodendrogliomas: reproducibility and prognostic value of histologic diagnosis
      and grading.
AB  - Prognostic value of histological grading of oligodendroglial tumors is
      controversial and interobserver reproducibility in grading of these tumors is
      unknown. Seven neuropathologists and 6 surgical pathologists experienced in brain
      tumor-diagnosis assessed 124 oligodendroglial tumors operated at the Mayo Clinic
      (1960-1990). Among histologic parameters upon which current oligodendroglioma
      grading systems are based, only high cellularity, presence of mitoses,
      microcalcifications, endothelial hypertrophy, endothelial proliferation, and
      necrosis appeared to be reproducible. Reproducible histologic features, based on
      consensus ratings among neuropathologists (defined as > 60%), were evaluated for
      the association with cause-specific survival by fitting Cox regression models. By
      univariate analysis, a significant association with survival was found for age,
      high cellularity, presence of mitoses, endothelial hypertrophy and proliferation
      and necrosis. On multivariable analysis with a stepwise variable selection
      method, only age and presence of endothelial proliferation were found to be
      independently associated with survival with a discriminatory index of the model
      of 0.68. Mitotic index was significantly associated with survival based on the
      grading from each separate neuropathologist, but it was not based on consensus,
      most likely because this was classified as indeterminate in 54% of cases.
      Alternatively, "models fit" considering the assessment of single
      neuropathologists, identified a model based on age and on mitotic index with
      similar discriminatory indices of 0.69-0.7. Our study found few factors
      independently associated with cause specific-survival among morphological
      parameters. These findings are consistent with the present WHO stratification of
      oligodendrogliomas into low- and high-grade variants.

PMID- 11245211
TI  - Analysis of cerebral amyloid angiopathy in a transgenic mouse model of Alzheimer
      disease using in vivo multiphoton microscopy.
AB  - Transgenic mice overexpressing the human amyloid precursor protein (APPV717F)
      develop cerebral amyloid angiopathy (CAA) as they age. We have examined the
      effect of CAA on blood vessels in vivo using multiphoton laser scanning
      microscopy. We are able to simultaneously detect, in an alive but anesthetized
      animal, fluorescent angiography of microvessels as well as the presence of
      amyloid angiopathy in 3-dimensional volumes near the surface of the brain.
      Analysis revealed dilation of the portions of vessels that were associated with
      amyloid deposition, even when that amyloid deposition was quite mild. In
      addition, analysis of the 3-dimensional reconstruction of the relationship
      between the vasculature and CAA suggest that CAA is initiated close to branch
      points of vessels. Taken together, these data suggest that CAA has a substantial
      effect on the physiology of the microvasculature in vivo.

PMID- 11245210
TI  - Effect of NGF and neurotrophin-3 treatment on experimental diabetic autonomic
      neuropathy.
AB  - Peripheral neuropathy is a significant complication of diabetes resulting in
      increased patient morbidity and mortality. Deficiencies of neurotrophic
      substances (e.g. NGE NT-3, and IGF-I) have been proposed as pathogenetic
      mechanisms in the development of distal symmetrical sensory diabetic
      polyneuropathy, and salutary effects of exogenous NGF administration have been
      reported in animal models. In comparison, relatively little is known concerning
      the effect of NGF on experimental diabetic sympathetic autonomic neuropathy. We
      have developed an experimental animal model of diabetic autonomic neuropathy
      characterized by the regular occurrence of pathologically distinctive dystrophic
      axons in prevertebral sympathetic ganglia and ileal mesenteric nerves of rats
      with chronic streptozotocin (STZ)-induced diabetes. Treatment of STZ-diabetic
      rats for 2-3 months with pharmacologic doses of NGF or NT-3, neurotrophic
      substances with known effects on the adult sympathetic nervous system, did not
      normalize established neuroaxonal dystrophy (NAD) in diabetic rats in the
      prevertebral superior mesenteric ganglia (SMG) and ileal mesenteric nerves as had
      pancreatic islet transplantation and IGF-I in earlier experiments. NGF treatment
      of control animals actually increased the frequency of NAD in the SMG. New data
      suggests that, in adult sympathetic ganglia. NGF may contribute to the
      pathogenesis of NAD rather than its amelioration, perhaps as the result of
      inducing intraganglionic axonal sprouts in which dystrophic changes are
      superimposed. NT-3 administration did not alter the frequency of NAD in diabetic
      animals, although it resulted in a significant decrease in NAD in control SMG.
      Although deficiencies of neurotrophic substances may represent the underlying
      pathogenesis of a variety of experimental neuropathies, delivery of excessive
      levels of selected substances may produce untoward effects.

PMID- 11245212
TI  - Distribution of tripeptidyl peptidase I in human tissues under normal and
      pathological conditions.
AB  - Tripeptidyl peptidase I (TPP I) is a lysosomal exopeptidase that cleaves
      tripeptides from the free N-termini of oligopeptides. Mutations in this enzyme
      are associated with the classic late-infantile form of neuronal ceroid
      lipofuscinosis (CLN2), an autosomal recessive disorder leading to severe brain
      damage. To gain more insight into CLN2 pathogenesis and the role of TPP I in
      human tissues in general, we analyzed the temporal and spatial distribution of
      TPP I in the brain and its localization in internal organs under normal and
      pathological conditions. We report that TPP I immunoreactivity appears in neurons
      late in gestation and increases gradually in the postnatal period, matching
      significantly the final differentiation and maturation of neural tissue.
      Endothelial cells, choroid plexus, microglial cells, and ependyma showed TPP I
      immunostaining distinctly earlier than neurons. Acquisition of the adult pattern
      of TPP I distribution in the brain at around the age of 2 years correlates with
      the onset of clinical signs in CLN2 subjects. In adults, TPP I was found in all
      types of cells in the brain and internal organs we studied, although the
      intensity of TPP I labeling varied among several types of cells and showed a
      noticeable predilection for cells and/or organs associated with peptide hormone
      and neuropeptide production. In addition, TPP I immunoreactivity was increased in
      aging brain, neurodegenerative and lysosomal storage disorders, and some
      differentiated neoplasms and was reduced in ischemic/anoxic areas and
      undifferentiated tumors. These findings suggest that TPP I is involved in general
      protein turnover and that its expression may be controlled by various regulatory
      mechanisms, which highlights the importance of this enzyme for normal function of
      cells and organs in humans.

PMID- 11245213
TI  - Amelioration of neurotoxic effects of HIV envelope protein gp120 by fibroblast
      growth factor: a strategy for neuroprotection.
AB  - Approximately two thirds of patients with human immunodeficiency virus
      encephalitis (HIVE) show cognitive impairment and neurodegeneration, while one
      third are cognitively unimpaired and their neuronal populations are preserved.
      Thus, it is possible that these individuals might have the capacity to produce
      neurotrophic factors capable of protecting neurons against the deleterious
      effects of HIV. In this context, the main objective of this study was to
      determine whether fibroblast growth factor 1 (FGF1) is protective against HIV.
      For this purpose levels of FGF1 immunoreactivity were determined in the frontal
      cortex of 35 AIDS cases subdivided into 4 groups according to the presence or
      absence of HIVE and neurodegeneration. In cases without both HIVE and
      neurodegeneration, mild to moderate levels of FGFI immunoreactivity were observed
      in pyramidal neurons, while in cases with HIVE but without neurodegeneration,
      levels were significiantly elevated. In contrast, individuals with both HIVE and
      neurodegeneration showed low levels of neuronal FGF1 immunoreactivity.
      Furthermore, studies in primary human neuronal cultures treated with the HIV
      envelope protein-gp120 in the presence or absence of FGF1 showed that FGF1 was
      protective against gpl20 neurotoxicity in a dose-dependent manner. Taken
      together, these results support the notion that upregulation of certain
      neurotrophic factors, such as FGF1, might protect the central nervous system from
      the neurotoxic effects of HIV.

PMID- 11245214
TI  - Caspase 3 expression correlates with skeletal muscle apoptosis in Duchenne and
      facioscapulo human muscular dystrophy. A potential target for pharmacological
      treatment?
AB  - Apoptosis was detected in different muscular diseases, including severe
      dystrophin deficiency, but apoptotic mechanisms are not completely described in
      adult skeletal muscle. Studying patients affected by Duchenne muscular dystrophy
      (DMD) and by facio-scapulo-humeral dystrophy (FSHD) we showed an increase of
      apoptotic myonuclei, bax, and bcl-2-positive myofibers. Positive correlation was
      detected between apoptotic nuclei and bax expression (p < 0.01). Expression of
      caspases was analyzed by RNase protection. Caspase transcript was not detected in
      normal skeletal muscles. DMD muscles expressed caspase 8, 3, 5, 2, 7 and Granzyme
      B mRNAs. Low levels of caspase 6, 3, and Granzyme B transcripts were detected in
      FSHD patients. Tissue levels of caspase 3 protein significantly correlated with
      apoptotic myonuclei (p < 0.05) and with bax expression (p < 0.01). In all DMD
      cases the activity of caspase 3 was increased, while the FSHD samples were
      heterogeneous. These data indicate that human skeletal muscle fibers. during the
      dystrophic process, modulate the expression of caspases and that caspase 3 is
      involved in myofiber cell death. opening new perspective in the pharmacological
      treatments of muscular dystrophies, such as the use of caspase inhibitors.

PMID- 11245215
TI  - A comparative study of the immunity region of lambdoid phages including Shiga
      toxin-converting phages: molecular basis for cross immunity.
AB  - Comparison of eight lambdoid phages, including three Shiga-toxin converting
      phages, has been carried out with respect to the immunity region, especially the
      recognition helices of their repressor and CRO proteins on the one hand, and
      operator sequences on the other. Some as yet unassigned components of the
      regulatory circuits have been inferred by computer search. The cross immunity
      phenomenon shown by phages VT2-Sa and lambda is explained on the basis of
      similarity in their sequences. In addition, the similarity of 933W and HK022 in
      the sequences of their recognition helices of repressor and CRO, on the one hand,
      and operators, on the other, has led us to predict that they will have identical
      or similar immunity specificity. This homology has enabled us also to locate the
      OL (and consequently PL) of phage 933W that has been thought to be non-existent.

PMID- 11245216
TI  - Identification and characterization of Thermus thermophilus HB8 RuvA protein, the
      subunit of the RuvAB protein complex that promotes branch migration of Holliday
      junctions.
AB  - The Escherichia coli ruvA and ruvB genes constitute an SOS-regulated operon. The
      products of these genes form a protein complex that promotes branch migration of
      the Holliday junction, an intermediate of homologous recombination. RuvA protein
      binds specifically to the Holliday junction and recruits RuvB protein to the
      junction. RuvB is an ATP-driven motor protein involved in branch migration. We
      previously cloned the ruvB gene of the thermophilic bacterium Thermus
      thermophilus HB8 (Tth) and found that, in contrast to the operon structure in
      most mesothermic bacteria, the ruvA gene is absent from the vicinity of ruvB. In
      this work, we cloned the ruvA gene from T. thermophilus HB8 and analyzed its
      nucleotide sequence. Tth RuvA is a protein of 20,414 Da consisting of 191 amino
      acid residues, and is 37% identical in amino acid sequence to E. coli RuvA. Tth
      ruvA complemented the DNA repair defect of E. coli deltaruvA mutants. The
      purified Tth RuvA protein stimulated Tth RuvB activities, such as hydrolysis of
      ATP and promotion of branch migration of the Holliday junction, in a manner
      similar to the RuvA-RuvB interactions observed in E. coli. In addition, Tth RuvA
      stimulated the E. coli RuvB activities in vitro, which was well consistent with
      the results of in vivo hetero-complementation experiments.

PMID- 11245217
TI  - Comparison of Waxy gene regulation in the endosperm and pollen in Oryza sativa L.
AB  - The Waxy (Wx) gene controls amylose synthesis in rice (Oryza sativa) and its
      expression is regulated organ-specifically. The Wx gene is expressed in the
      endosperm and pollen but not in other organs. In order to know whether Wx gene
      regulation is the same in the endosperm and pollen, we compared expression
      patterns of the rice Wx gene in these two organs by immunoblot analysis. We
      focused on the allelic differences (Wxa and Wxb), cool temperature response and
      effects of the mutation at the du loci. The results obtained are as follows.
      First, the quantitative regulation depending on two alleles, Wxa and Wxb, was
      common to both organs; Wx protein levels from the Wxa allele were about 10-fold
      higher than those from the Wxb allele in the pollen as well as in the endosperm.
      Second, in both the endosperm and pollen, expression of the Wxb gene, but not the
      Wxa gene, was enhanced in response to cool temperature. In contrast to these two
      types of regulation, analysis of two du mutants, 2035 (du1) and 76-3 (du2),
      revealed that the pattern of reduction in Wx protein levels in the pollen was
      distinct from that in the endosperm, suggesting that functions of the two du+
      genes differ in these two organs.

PMID- 11245218
TI  - Compensating ability in pollen fertilization between group-6 and -7 homoeologous
      chromosomes of barley and wheat.
AB  - By using alpha-amylase isozymes as markers for chromosomes of homoeologous groups
      6 and 7, we analyzed the segregation of chromosome constitution in the progenies
      from crosses between double-ditelosomic or ditelosomic lines of hexaploid wheat
      cultivar 'Chinese Spring' (CS) as the female parent and double-monosomic F1
      hybrids of CS x wheat-barley substitution lines for barley chromosomes 6H or 7H.
      From this analysis we estimated the transmission rate via pollen of barley
      chromosomes 6H and 7H in the double-monosomics and evaluated the compensating
      ability between barley and wheat chromosomes in homoeologous groups 6 and 7. The
      results indicated that both 6H and 7H showed their highest compensating ability
      for their respective homoeologous wheat chromosomes 6A (37.5% transmission rate)
      and 7A (39.4%), intermediate for 6D (34.1%) and 7D (29.6%), and lowest for 6B
      (26.6%) and 7B (22.6%) chromosomes.

PMID- 11245220
TI  - Genetic microstructure in two Spanish cat populations. I: genic diversity, gene
      flow and selection.
AB  - The genetic microstructure of two Spanish cat populations (in Barcelona and
      Alicante) was studied. These populations were in Hardy-Weinberg equilibrium at
      the locus O . There was significant genetic heterogeneity for most of the loci
      studied at the colony level, especially, and the subpopulation level in
      Barcelona, and at the subpopulation level in Alicante, although the amount of
      heterogeneity was relatively small compared with that found in other mammal
      species. Therefore, the major part of the gene diversity found was at the level
      of the small population structure (colonies). This agrees quite well with high
      theoretical gene flow estimates. The Lewontin-Krakauer test showed, in some
      cases, significant F tests, which appears to indicate the presence of several
      selective events on some of the loci studied (diversifying and/or unifying),
      although some other causes, such as differential gene flow, some different
      historical and demographic parameters at the time of the introduction of the
      different alleles within the cities studied, as well as different mutation rates
      of the loci analyzed, could produce significant Lewontin-Krakauer test values, as
      well.

PMID- 11245219
TI  - Evolutionary trends of the mitochondrial lineage differentiation in species of
      genera Martes and Mustela.
AB  - We compared partial sequences (402 bp) of the mitochondrial cytochrome b gene in
      68 individuals of martens (Martes), weasels (Mustela) and their relatives from
      the Northern Hemisphere to identify the modes of geographic differentiation in
      each species. We then compared complete sequences (1140 bp) of the gene in 17
      species of the family Mustelidae to know the spatial and temporal modes of
      speciation, constructing linearized trees with transversional substitutions for
      deeper lineage divergences and with transversions and transitions for younger
      lineages. Our data suggested that these lineages of Martes and Mustela
      differentiated in a stepwise fashion with five radiation stages from the generic
      divergences (stage I) to the intraspecific divergences (stage V), during the last
      10 or 20 million years as the fossil evidence suggests. In the lineage of Martes,
      the first offshoots are of Martes flavigula, M. pennanti, and Gulo gulo (stage
      II), the second is M. foina (stage III), and the third are M. americana, M.
      martes, M. melampus, and M. zibellina (stage IV). The divergence of the lineages
      of Mustela is likely to have taken place concurrently with the radiations of the
      Martes. These divergence processes are attributable in part to the geographic
      allocation along the two continents, North America and Eurasia, as well as among
      peripheral insular domains, such as Taiwan and the Japanese Islands. In addition,
      the Eurasian continent itself was shown to have been involved in the species
      diversification in the martens and weasels.

PMID- 11245221
TI  - Genetic microstructure in two Spanish cat populations. II: gametic disequilibrium
      and spatial autocorrelation.
AB  - In a previous publication, we described some aspects of the microgenetic
      structure of two Spanish cat populations (in Barcelona and Alicante). In the
      present study, the possible existence ofgametic disequilibrium and spatial
      genetic structure for these populations, at the coat colour pattern and length
      genes O, A, T D, L, S and W, was analyzed. There was little gametic
      disequilibrium between pairs of these loci, despite certain pairs that showed
      significant systematic gametic disequilibrium (a-d and O-S), which appears to
      show the action of natural selection on domestic cat populations. Nevertheless,
      we believe that the major cause of the small amount of gametic disequilibrium
      found was probably a combination of gene drift and gene flow. The results
      obtained here were clearly in disagreement with those of Hedrick (1985), who
      concluded that epistatic selection was the cause of the gametic disequilibrium
      that he found in cat populations. We also found that although Hardy-Weinberg
      equilibrium could not be demonstrated, the gametic disequilibrium statistics were
      not affected by this fact, adding credence to the estimates obtained. We found no
      genetic spatial structure inside the city of Barcelona, as shown by analysis of
      the spatial autocorrelation of the individual loci, and analysis of the
      coordinates of the two first axes of a multidimensional scale. However, some
      gametic disequilibrium statistics showed certain spatial patterns, which leads us
      to consider the possibility of several evolutionary processes acting upon some of
      Barcelona's cat colonies.

PMID- 11245222
TI  - cDNA cloning and molecular analysis of papaya small GTP-binding protein, pgp1.
AB  - In the course of papaya EST collection, one clone (pRA4-3) encoding partial
      sequence of papaya small GTP-binding protein gene, pgp1, was obtained. Based on
      the sequence information of pRA4-3, the entire coding region of pgp1 was cloned
      using the 3'RACE PCR technique. ORF of pgp1 is 636bp long and deduced molecular
      weight of the protein is 23,311. Phylogenetic analysis showed that PGP1 belongs
      to YPT/RAB group of the small GTP-binding protein and is a homologue of RAB2.
      Southern analysis showed that there are several pgp1-related genes in papaya
      genome. Northern analysis showed that pgp1 was expressed equally in stems of
      seedlings that were grown under light and dark conditions. This result shows that
      PGP1 is not involved in the phytochrome-mediated signal transduction as an auxin
      signal transducer in stems of papaya seedlings.

PMID- 11245224
TI  - Kinetics and mechanism of gas-phase thermolysis using headspace-gas
      chromatographic analysis.
AB  - Headspace gas chromatography is employed in order to study the thermal
      decomposition reaction of gaseous di-tert-butyl peroxide (DTBP) in the 130
      degrees C to 160 degrees C temperature range and in the presence of n-hexane as
      the internal standard and nitrogen as the carrier gas. The reaction exclusively
      yields acetone and ethane as products. First-order kinetics are observed,
      including when the surface-to-volume ratio (S/V) of the Pyrex 20-mL vial employed
      as the reactor is increased by packing it with silanized glass wool. However, a
      small increase in the rate constant values is observed at each temperature, which
      supports a heterogeneous surface process in DTBP decomposition. The rate
      constant's dependence on the homogeneous unimolecular decomposition reaction
      corresponds to the O-O bond rupture of the DTBP molecule in a stepwise three
      stage mechanism. Thus, the relevant question of the participation of a surface
      catalytic effect in the DTBP gas-phase thermolysis can easily be assessed through
      the procedure described in this work. In general, this is advantageous for the
      rapid investigation of the reaction kinetics of volatile compounds at different
      temperatures.

PMID- 11245223
TI  - Chromosomal localization of 18S rDNA and telomere sequence in the aye-aye,
      Daubentonia madagascariensis.
AB  - Chromosomal localization of 18S rDNA and telomere sequence was attempted on the
      chromosomes of the aye-aye (2n = 30) using fluorescence in situ hybridization
      (FISH) and primed in situ labeling (PRINS), respectively. The rDNA was localized
      at the tip or whole of the short arm of acrocentric chromosomes 13 and 14 in all
      spreads observed. However, post-FISH silver-nitrate (Ag) staining showed that
      transcriptional activity of the rRNA genes was variable, particularly in
      chromosome 14, which was most frequently negative in one homologue carrying the
      smaller copy number of rDNA. This observation supports, at the molecular
      cytogenetic level, previous data concerning the relationship between the copy
      number of rDNA and its trancriptional activity. On the other hand, telomere
      sequence was localized only at the telomeric region of all chromosomes, the so
      called telomere-only pattern, a characteristic similar to that of the greater
      bushbaby. These data may provide information on the chromosomal evolution of the
      lemur, because locations of rDNA and telomere sequences frequently offer
      important clues in reconstruction of karyotype differentiation.

PMID- 11245226
TI  - Characterization of formaldehyde by gas chromatography using multiple pulsed
      discharge photoionization detectors and a flame ionization detector.
AB  - Formaldehyde, water, methanol, butanal, and butanone are characterized by gas
      chromatography using three pulsed-discharge photoionization detectors (PDPIDs)
      and a flame ionization detector (FID). One of the PDPIDs is operated in helium
      mode, and the other two are operated in argon and krypton modes. The FID is
      included for comparison. The PDPIDs are used to efficiently differentiate between
      and quantitatively identify formaldehyde and the other three compounds in a
      sample mixture. This is accomplished by using butanone as the internal standard
      and correlating the relative responses of the four organic compounds in the
      helium-, argon-, and krypton-mode PDPIDs with their relative retention times.

PMID- 11245225
TI  - Determination of bromethalin in commercial rodenticides found in consumer product
      samples by HPLC-UV-vis spectrophotometry and HPLC-negative-ion APCI-MS.
AB  - A small amount of green particulate material is encountered in a consumer
      complaint sample. The green particulates in the sample are identified as a
      bromethalin-containing rodenticide using high-performance liquid chromatographic
      (HPLC)-UV-vis spectrophotometric and HPLC-negative-ion atmospheric pressure
      chemical ionization (APCI)-mass spectrometric (MS) approaches, which are commonly
      used for the detection and confirmation of bromethalin in grain-based
      rodenticides. The selective and sensitive nature of the MS detector makes it
      possible to determine bromethalin without extensive sample cleanup and
      preconcentration. The estimated detection limit with the UV-vis detector is 500
      pg of bromethalin injected into the column. The extensive fragmentation of the
      bromethalin molecule under APCI conditions provides sufficient structural
      information for positive identification.

PMID- 11245227
TI  - Quantitative analysis of hydrocortisone in human urine using a high-performance
      liquid chromatographic-tandem mass spectrometric-atmospheric-pressure chemical
      ionization method.
AB  - In this study, the development and validation of a method of analysis for
      11,17,21,-trihydroxypregn-4-ene-3,20-dione (hydrocortisone, cortisol, HC) using
      high-performance liquid chromatography (HPLC)-tandem mass spectrometry (MS) with
      atmospheric-pressure chemical ionization (APCI) is reported. This is the first
      report of the systematic development and validation of an HPLC-MS-MS method for
      the quantitation of HC in synthetic human urine with a deuterated internal
      standard. Prior to LC-MS-MS analysis, the only sample preparation used was the
      dilute-and-shoot technique prior to LC-MS-MS analysis. In this study, an analysis
      time of less than 3 min is achieved. The results show freedom of interference
      from other analytes such as analogous steroids. Validation parameters such as
      specificity/selectivity, limit of quantitation (LOQ), linearity, precision,
      accuracy, ruggedness, stability, and system suitability are evaluated for this
      method. The LOQ is 5 ng/mL with an 8% relative standard deviation (RSD). For
      calibration standard curves, an average linear response for a 3-day validation
      (R2 = 0.997) over the range of 5 to 500 ng/mL is obtained. The interday precision
      %RSDs are 7.2, 5.0, and 5.2 for 15, 75, and 300 ng/mL, respectively. Also, brief
      comparisons of the dilute-and-shoot and liquid-liquid extraction techniques for
      this analyte are discussed.

PMID- 11245228
TI  - Very-large-volume sampling of water in gas chromatography using the through oven
      transfer adsorption desorption (TOTAD) interface for pesticide-residue analysis.
AB  - The Through Oven Transfer Adsorption Desorption (TOTAD) interface is used to
      directly introduce large volumes of water (1 mL or more) into a capillary gas
      chromatograph. The TOTAD interface is a greatly modified programmed temperature
      vaporizer injector incorporating changes that affect the pneumatics, sample
      introduction, solvent elimination, and operation mode. The system can easily be
      automated. The technique is applied to the analysis of pesticide residue in
      standard solutions and real water samples from the Ebro River (northeastern
      Spain). The speed of sample introduction was 1 mL/min, and the solvent
      elimination was almost complete. A nitrogen phosphorous detector is used, and the
      relative standard deviation varied from 5.7% to 11.7% for the absolute peak
      areas. The sensitivity achieved by introducing 1 mL of the sample is sufficient
      for most pesticide-residue analyses in water. The limits of detection ranged from
      0.5 to 8.1 ng/L.

PMID- 11245229
TI  - A liquid chromatographic method for the simultaneous determination of
      promethazine and three of its metabolites in plasma using electrochemical and UV
      detectors.
AB  - A new assay method has been developed for the quantitation of promethazine (PMZ)
      with a sensitivity and reproducibility as good as any previously reported method.
      This method is also capable of quantitatively determining three metabolites of
      PMZ (monodemethylated, sulphoxidated, and monodemethylated sulphoxidated PMZ),
      which has not been previously described. The method uses high-performance liquid
      chromatography with amperometric and UV detection simultaneously and requires
      only one extraction step from serum with chloroform. The method uses
      trifluoperazine as the internal standard. The limit of detection level for PMZ is
      1.0 ng/ml when a 0.2-mL specimen of plasma is assayed. A validation study is also
      conducted for evaluating the recovery, precision, linearity of response,
      sensitivity, and selectivity of the method.

PMID- 11245230
TI  - Gas chromatographic determination of 1,4-dioxane at low parts-per-million levels
      in glycols.
AB  - 1,4-Dioxane is a flammable liquid and tends to form explosive peroxides. Its
      formation in glycols (low parts-per-million levels), which are used as
      dehumidifying agents in refineries, may take place by condensation. 1,4-Dioxane
      thus formed gets distilled over with benzene in the refinery process. Therefore,
      it is necessary to identify and determine the levels of 1,4-dioxane in glycols as
      well as benzene. Gas chromatography (GC) is probably the best technique for this
      purpose. GC analysis may be carried out using a flame ionization detector.
      Results show that 1,4-dioxane can be comfortably determined down to 2 ppm in
      glycols and benzene.

PMID- 11245231
TI  - Why is it important to control the pH of an eluent when carrying out most
      reversed-phase HPLC separations, and how does pH affect a solute's retention and
      the reproducibility of an assay?

PMID- 11245232
TI  - Magnetic resonance imaging features of multilobular osteochondrosarcoma in 3
      dogs.
AB  - Three dogs with multilobular osteochondrosarcoma of the skull were evaluated
      using magnetic resonance (MR) imaging. Spin echo T1, T2, proton weighted and post
      contrast T1W images were obtained with a 1.5 Tesla magnet. The MR imaging
      findings were similar in all three dogs with mixed signal intensities in the T1W,
      T2W and proton weighted images and fairly large areas of contrast enhancement in
      the post contrast T1W images. The extent of brain and soft tissue involvement
      were well delineated and provided useful information concerning surgical
      planning. MR imaging provided a useful method of evaluating dogs with skull
      tumors.

PMID- 11245233
TI  - Magnetic resonance imaging features of cervical stenotic myelopathy in 21 dogs.
AB  - The cervical spine of 21 dogs with clinical signs of cervical stenotic myelopathy
      was evaluated using magnetic resonance (MR) imaging. Spin echo T1, T2 and
      gradient echo T2 weighted images were obtained with a 1.5 Tesla magnet in 12 dogs
      and a 1.0 Tesla magnet in 9 dogs. Sagittal or parasagittal T1W and T2W images
      were helpful in determining the presence of spinal cord compression or
      degenerative disease of the articular processes. Transverse T1W and T2W images
      were the most useful for the identification of dorsolateral spinal cord
      compression secondary to soft tissue and ligament hypertrophy, as well as
      synovial cysts, associated with the articular processes. The MR imaging findings
      were consistent with the surgical findings in all 14 dogs that underwent surgery.
      Magnetic resonance imaging provided a safe, non-invasive method of evaluating the
      cervical spine in dogs suspected of having cervical stenotic myelopathy.
      Veterinary

PMID- 11245234
TI  - Thoracic radiographic appearance in the normal llama.
AB  - The goal of this study was to collect quantitative and qualitative radiographic
      information of the normal adult llama thorax. Standing right-left lateral
      radiographs of the thorax of 16 normal llamas were made. Normal ratios of cardiac
      height, width, and height plus width to thoracic vertebrae 3-5 and thoracic
      height were calculated. Normal values determined for tracheal angle of divergence
      from the thoracic spine, cardiophrenic and cardiosternal contact are additional
      potential indicators of cardiac enlargement. Ratios of normal pulmonary artery
      and vein, caudal vena cava and trachea to the height of the fourth thoracic
      vertebra should allow identification of pathology of these structures.
      Observations regarding pulmonary vessels and airways, thoracic spine, sternebrae
      and portions of the gastrointestinal tract observed on thoracic radiographs are
      also included. It is proposed that these normal values and observations can be
      used to better evaluate diseases of the cardiovascular and respiratory systems of
      adult llamas.

PMID- 11245235
TI  - Multicentric lymphosarcoma in a dog with multiple-site skeletal involvement.
AB  - In this report the authors describe an unusual clinical presentation of
      lymphosarcoma (LSA) in a dog. A 9-year-old, neutered male, Golden Retriever was
      presented with a primary complaint of sudden onset of tetraparesis. Routine
      survey radiographs revealed multiple-site bony lesions and the histology revealed
      a diagnosis of LSA with diffuse skeletal and soft tissue involvement. The dog
      responded poorly to medical management and was euthanized on day two due to poor
      prognosis. Malignant LSA of the bone is a rare extranodal clinicopathologic
      entity and presents both a diagnostic and therapeutic hurdle. Reports of this
      kind are sparse and currently no optimal treatment for this entity has been
      determined.

PMID- 11245236
TI  - Vertebral angiomatosis in a cat.

PMID- 11245237
TI  - A retrospective study into the effects of operator experience on the accuracy of
      ultrasound in the diagnosis of gastric neoplasia in dogs.
AB  - The accuracy of three diagnostic techniques in two separate time periods was
      examined. In the first time period, 18 dogs were referred to the University of
      Bristol with signs suggestive of gastric neoplasia. Of these 18 dogs, 7 had a
      positive diagnosis of gastric neoplasia from histopathology samples (38%
      prevalence). The sensitivity of ultrasound was found to be 42.9% with a
      specificity of 63.6%. A year later the study was repeated with 40 cases referred
      for investigation. Of these 40 dogs, 16 had a positive histopathologic diagnosis
      of gastric neoplasia (40% prevalence). At this time the sensitivity of ultrasound
      had increased to 81.3 % and the specificity had increased to 70.8 %. The increase
      in sensitivity was attributed to an increase in operator experience in the
      performance of the ultrasound examination. This improvement in sensitivity and
      experience resulted in a greater accuracy at detecting the presence of gastric
      neoplasia.

PMID- 11245239
TI  - Mitral annulus motion as determined by M-mode echocardiography in normal dogs and
      dogs with cardiac disease.
AB  - M-mode echocardiography was used to assess apical mitral annulus motion (MAM) in
      103 normal dogs and 101 dogs with cardiac disease, to obtain information on
      systolic left ventricular long axis function. In normal dogs, a close
      relationship was found between MAM and body weight (r = 0.80, P < 0.001). There
      was a weak correlation between MAM and heart rate (r = -0.25, P < 0.05), but no
      correlation between MAM and age or left ventricular shortening fraction (P >
      0.05). Mean MAM (95% confidence intervals) were established for normal dogs of
      differing body weight, and were 0.70 cm (0.65 to 0.75) in dogs < 15 kg, 1.08 cm
      (1.03 to 1.13) in dogs weighing 15 to 40 kg, and 1.51 cm (1.21 to 1.81) in dogs >
      40 kg. "Cut-off" values to define decreased MAM for normal dogs of differing body
      weight were 0.45 cm (dogs < 15 kg), 0.80 cm (dogs 15-40 kg), and 1.20 cm (dogs >
      40 kg). In dogs with cardiac disease, median MAM was normal in mitral valve
      endocardiosis or aortic stenosis, but significantly decreased (P < 0.05) in
      dilated cardiomyopathy. All dogs with mitral valve endocardiosis (n = 54) or
      aortic stenosis (n = 26) had MAM above the above-mentioned "cut-off" values,
      suggesting normal or increased left ventricular longitudinal systolic shortening,
      whereas 81% (17/21) of dogs with dilated cardiomyopathy had MAM below the "cut
      off" value, indicating decreased long axis systolic function. It is concluded
      that MAM may be used to evaluate systolic left ventricular long axis performance
      in dogs and may add useful information on global left ventricular contraction
      dynamics.

PMID- 11245238
TI  - Magnetization transfer imaging of the canine brain: a review.
AB  - Magnetization transfer imaging is a modality capable of examining the non-water
      components of brain tissue by examining the effects they have on water protons.
      It may be used qualitatively to increase the visibility of lesions seen during
      magnetic resonance angiography and following the administration of an intravenous
      paramagnetic contrast medium. Quantitatively, it can be used to examine the
      effect of pathology on magnetization transfer contrast, to provide a measurement
      of myelination, as well as to quantify disease progression in trauma, neoplasia,
      neurodegeneration and other disorders of the brain. This paper reviews the theory
      of magnetization transfer imaging, its applications, and provides an example of
      its use in examining the canine brain.

PMID- 11245240
TI  - The use of gated radionuclide ventriculography as a noninvasive method of
      evaluating right ventricular function in dogs with experimentally induced
      congestive heart failure.
AB  - Gated radionuclide ventriculography was evaluated as a noninvasive method of
      quantifying right ventricular function in dogs with experimentally induced
      congestive heart failure. Gated radionuclide ventriculography measurements of
      right ventricular function (right ventricular ejection fraction, right
      ventricular average emptying rate, and right ventricular average filling rate)
      were related to standard hemodynamic and echocardiographic measurements.
      Congestive heart failure was induced by rapid ventricular pacing in eight normal
      dogs. Hemodynamic, echocardiographic, and gated radionuclide ventriculography
      measurements were obtained before and after development of biventricular failure.
      Congestive heart failure resulted in significant changes in all hemodynamic,
      echocardiographic, and gated radionuclide ventriculography measurements with the
      exception of systemic arterial pressure. Right ventricular ejection fraction was
      inversely related to pulmonary artery systolic, diastolic, and mean pressure, and
      right ventricular average emptying rate was inversely related to the pulmonary
      artery systolic, diastolic, and mean pressure. Right ventricular ejection
      fraction was inversely related to left ventricular filling pressure, (pulmonary
      capillary wedge pressure). Neither the echocardiographic measurements of right
      ventricular size (right ventricular internal diastolic dimension) nor the right
      ventricular end-diastolic pressure were related to right ventricular ejection
      fraction and right ventricular average emptying rate. However, echocardiographic
      measurements of right ventricular dimension were related to right ventricular
      filling pressure. The gated radionuclide ventriculography indexes of right
      ventricular function, right ventricular ejection fraction and right ventricular
      average emptying rate, are affected by afterload but unaffected by preload,
      whereas the echocardiographic measurement of right ventricular dimension is
      related to preload. Gated radionuclide ventriculography provides right
      ventricular data which is unique from that obtained by standard echocardiographic
      imaging. Also, gated radionuclide ventriculography has potential value as a
      noninvasive means of estimating a change in pulmonary artery pressure.

PMID- 11245241
TI  - Quantitative hepatobiliary scintigraphy in normal cats and in cats with
      experimental cholangiohepatitis.
AB  - Quantitative hepatobiliary scintigraphy using 99mTc-mebrofenin was performed on
      eight normal cats and on the same cats after induction of experimental
      cholangiohepatitis by infection with the liver fluke Platynosomum concinnum.
      Hepatobiliary scintigraphy was performed 3 times at 10 weeks, 4 months and 6
      months after infection. In addition, routine biochemical tests, hepatic
      ultrasound and ultrasound guided hepatic biopsy samples were obtained at the same
      time points, and the results compared with hepatobiliary scintigraphy. The normal
      hepatic extraction fraction was determined to be 85%, and the normal hepatic
      excretion half time (T 1/2) was 14 minutes. There was no significant change in
      scintigraphic parameters compared to pre-infection values at any time following
      infection with the liver fluke. No correlation between scintigraphic parameters
      and histologic scores was found; however, significant correlation was identified
      between parasite burden and histologic scores 6 months following infection.
      Despite the presence of severe multifocal histologic abnormalities, minimal
      clinical, biochemical and scintigraphic derangements were identified using this
      model of cholangiohepatitis. Based on this study, hepatobiliary scintigraphy
      appears to be an insensitive test for structural hepatobiliary abnormalities. The
      role of hepatobiliary scintigraphy in functional hepatobiliary abnormalities of
      the feline liver has not been determined.

PMID- 11245242
TI  - Response of feline oral squamous cell carcinoma to palliative radiation therapy.
AB  - Seven cats with advanced oral squamous cell carcinoma were treated with
      palliative radiotherapy. Megavoltage radiation in 8 Gray (Gy) fractions was
      delivered on days 0, 7, and 21 for a total dose of 24 Gy. Treatment field
      included the mandible, oropharynx, retropharyngeal lymph nodes, and tonsils.
      Adjuvant treatment with chemotherapy was variable. Age ranged from 13 to 18 years
      old with a median age of 15 years. Three of the seven cats (43%) did not complete
      treatment. Six cats were euthanized due to tumor growth and/or radiation side
      effects with a median survival time of 60 days (range = 42 to 97 days, mean = 63
      +/- 8.4 days). Radiotherapy complications or progression of disease occurred in 6
      of 7 (85.7 %) cats and included adverse clinical signs, such as mucositis,
      serosanguinous oral discharge, pain, and dysphagia. These data suggest that
      coarse fractionation radiotherapy did not result in palliation in cats with
      inoperable oral squamous cell carcinoma.

PMID- 11245243
TI  - ACVR 2000 oral certification examination: large animal elective.

PMID- 11245244
TI  - A pair of intranasal moose.

PMID- 11245245
TI  - MR imaging findings in a dog with lumbar ganglion cysts.
AB  - Intraspinal cysts of the L6-L7 and L7-S1 articular process joints in a six-year
      old neutered female German Shepherd Dog were diagnosed using magnetic resonance
      (MR) imaging. Histopathology provided a diagnosis of ganglion cysts. Clinical,
      laboratory, radiographic and MR imaging findings are described. Briefly,
      radiographic findings revealed lumbarization of the first sacral vertebra, and
      fusion of the first caudal vertebra to the sacrum. In addition, spondylosis and
      articular process osteoarthrosis occurred at L6-L7 and L7-S1. MR imaging revealed
      multiple, well encapsulated structures ranging in size from 3-10 mm in diameter
      which were found to arise from the L6-L7 and L7-S1 articular process joints.
      These cysts had signal intensities that varied from hyperintense to the
      cerebrospinal fluid (CSF) on T1 weighted images to isointense to CSF on T2
      weighted images. Decompressive surgery in conjunction with arthrodesis of these
      joints resulted in resolution of clinical signs. The dog remained pain-free 1 1/2
      years following surgical therapy.

PMID- 11245246
TI  - The telomeric dG(GT)4G sequence can adopt a parallel-stranded double helical
      conformation.
AB  - Oligonucleotides 3'-d(GTGTGTGTGG)-L-d(GGTGTGTGTG)-3' (hp-GT) and 3'
      d(G4STG4TG4STG4STGG)-L-d(GGTGTGTGTG)-3' (hp-SGT), (L=(CH2CH2O)3), were shown by
      use of several optical techniques to form a novel parallel-stranded (ps)
      intramolecular double helix with purine-purine and pyrimidine-pyrimidine base
      pairing. The rotational relaxation time of hp-GT was similar to that of a 10-bp
      reference duplex, and the fraction of unpaired bases was determined to be
      approximately 7%, testifying to the formation of an intramolecular double helical
      hairpin by the sequence under the given experimental conditions. A quasi-two
      state mode of ps-double helix formation was validated, yielding a helix-coil
      transition enthalpy of -135 +/- 5 kJ/mol. The G x G and T x T (or 4ST x T) base
      pair configurations and conformational parameters of the double helix were
      derived with molecular modeling by force field techniques. Repetitive d(GT)
      sequences are abundant in telomers of different genomes and in the regulatory
      regions of genes. Thus, the observed conformational potential of the repetitive
      d(GT) sequence may be of importance in the regulation of cell processes.

PMID- 11245248
TI  - Nucleosomal positioning and genetic divergence study based on DNA flexibility
      map.
AB  - Based on worm like chain model, DNA structural parameters--tilt, roll and rise,
      derived from crystallographic database have been used to determine the
      flexibility of DNA that regulates the nucleosomal translational positioning.
      Theoretically derived data has been compared to the experimental values available
      in loshikhes and Trifonov's database. The methodology has been extended to
      determine the flexibility of 18S rRNA genome in eukarya, where yeast shows a
      distinct difference when compared with mammals like human, mouse and rabbit.

PMID- 11245247
TI  - A refined prediction method for gel retardation of DNA oligonucleotides from
      dinucleotide step parameters: reconciliation of DNA bending models with crystal
      structure data.
AB  - The development and assessment of a prediction method for gel retardation and
      sequence dependent curvature of DNA based on dinulcleotide step parameters are
      described. The method is formulated using the Babcock-Olson equations for base
      pair step geometry (1) and employs Monte Carlo simulated annealing for parameter
      optimization against experimental data. The refined base pair step parameters
      define a stuctural construct which, when the width of observed parameter
      distributions is taken into account, is consistent with the results of DNA
      oligonucleotide crystal structures. The predictive power of the method is
      demonstrated and tested via comparisons with DNA bending data on sets of
      sequences not included in the training set, including A-tracts with and without
      periodic helix phasing, phased A4T4 and T4A4 motifs, a sequence with a phased
      GGGCCC motif, some "unconventional" helix phasing sequences, and three short
      fragments of kinetoplast DNA from Crithidia fasiculata that exhibit significantly
      different behavior on non-denaturing polyacrylamide gels. The nature of the
      structural construct produced by the methodology is discussed with respect to
      static and dynamic models of structure and representations of bending and
      bendability. An independent theoretical account of sequence dependent chemical
      footprinting results is provided. Detailed analysis of sequences with A-tract
      induced axis bending forms the basis for a critical discussion of the
      applicability of wedge models,junction models and non A-tract, general sequence
      models for understanding the origin of DNA curvature at the molecular level.

PMID- 11245249
TI  - Changes of nuclear structure induced by increasing temperatures.
AB  - Despite the recent improvement in understanding the higher-order structure of
      chromatin fibers, the organization of interphase chromosomes in specific nuclear
      domains emerged only recently and it is still controversial. This study took
      advantage of an integrated approach using complementary techniques in order to
      investigate the structure and organization of chromatin in interphase nucleus.
      Native CHO-K1 cells were progressively heated from 310 K to 410 K and the effects
      of increasing temperatures on nuclear chromatin were analyzed in situ by means of
      cytometric and calorimetric techniques. Distribution and organization of
      chromatin domains were analyzed by Fluorescence microscopy, while the mean
      condensation of nuclear chromatin was measured by Differential scanning
      calorimetry. The results show as changes of nuclear structures (envelope and
      matrix, namely) affect significantly organization and condensation of in situ
      chromatin. Moreover when volume is modified by an external force (the temperature
      gradient in our case) we observe significant alterations of chromatin structure.
      These data are in accordance with the hypothesis of an inverse relationship
      between nuclear volume and chromatin condensation.

PMID- 11245250
TI  - Quantum-chemical analysis of C-H...O and C-H...N interactions in RNA base pairs-
      H-bond versus anti-H-bond pattern.
AB  - Geometries and interaction energies of unusual UU and AA base pairs with one
      standard hydrogen bond (H-bond) and additional C-H...O or C-H...N contacts have
      been determined by quantum-chemical methods taking into account electron
      correlation. Whereas the C-H bond length in the UU C-H...O contact increases upon
      complex formation (H-bond pattern), the C-H bond of the AA C-H....N interaction
      is shortened (anti-H-bond pattern). The same properties are found for model
      complexes between U or A and formaldehyde that have intermolecular C-H...acceptor
      contacts but no standard H-bonds. Both the C-H...acceptor H-bond and anti-H-bond
      interactions are attractive. A possible influence of the donor CH group charge
      distribution on the interaction pattern is discussed.

PMID- 11245251
TI  - Papain does not cleave operator-bound lambda repressor: structural
      characterization of the carboxy terminal domain and the hinge.
AB  - The circular dichroism spectra of three different purified carboxy terminal
      fragments 93-236, 112-236 and 132-236 of the bacteriophage lambda cI repressor
      have been measured and compared with those of the intact repressor and the amino
      terminal fragment 1-92. All three carboxy terminal fragments contain mostly beta
      strands and loops, a minor helix content increasing with the size of the
      fragment, showing that the 93-131 region previously called a hinge is structured.
      Fourier transformed infrared spectra also showed that fragment 93-236 contains
      alpha-helices, alpha-sheets and turns but fragment 132-236 contains no detectable
      alpha-helix, only beta-sheets and turns. Papain is known to cleave the lambda
      repressor, but it is shown here that it cannot cleave the operator-bound
      repressor dimer. For the 132-236 fragment, both the wt and the SN228 mutant
      previously shown to be dimerization defective in the intact, gave similar
      dimerization properties as investigated by HPLC at 2 to 100 microM protein
      concentration, with a KD of 13.2 microM and 19.1 microM respectively. The papain
      cleavage for wt and SN228 proceed at equal rates for the first cleavage at 92-93;
      however, the subsequent cleavages are faster for SN228. The three Cys residues in
      the 132-236 fragment were found to be unreactive upon incubation with DTNB,
      indicating the thiol sulfur atoms are buried in the repressor carboxy terminal
      domain. Denaturation of the 132-236 fragment studied by tryptophan fluorescence
      shows two transitions centered at 1.5 M and 4.5 M of urea.

PMID- 11245253
TI  - Conformational preferences of heterochiral peptides. Crystal structures of
      heterochiral peptides Boc-(D) Val-(D) Ala-Leu-Ala-OMe and Boc-Val-Ala-Leu-(D) Ala
      OMe--enhanced stability of beta-sheet through C-H...O hydrogen bonds.
AB  - The crystal structures of Boc-(D) Val-(D) Ala-Leu-Ala-OMe (vaLA) and Boc-Val-Ala
      Leu-(D) Ala-OMe (VALa) have been determined. vaLA crystallises in space group
      P2(1),2(1),2(1), with a = 9.401 (4), b = 17.253 (5), c = 36.276 (9)A. V = 5,884
      (3) A3, Z = 8, R = 0.086. VALa crystallises in space group P2(1) with a = 9.683
      (9), b = 17.355 (7), c = 18.187 (9) A, beta = 95.84 (8) degrees , V = 3,040(4)
      A3, Z = 4, R = 0.125. There are two molecules in the asymmetric unit in
      antiparallel beta-sheet arrangement in both the structures. Several of the Calpha
      hydrogens are in hydrogen bonding contact with the carbonyl oxygen in the
      adjacent strand. An analysis of the observed conformational feature of D-chiral
      amino acid residues in oligopeptides, using coordinates of 123 crystal structures
      selected from the 1998 release of CSD has been carried out. This shows that all
      the residues except D-isoleucine prefer both extended and alphaL conformation
      though the frequence of occurence may not be equal. In addition to this, D
      leucine, valine, proline and phenylalanine have assumed alphaR conformations in
      solid state. D-leucine has a strong preference for helical conformation in linear
      peptides whereas they prefer an extended conformation in cyclic peptides.

PMID- 11245252
TI  - Recognition and stabilization of a unique CPRI--structural motif in cucurbitaceae
      family trypsin inhibitor peptides: molecular dynamics based homology modeling
      using the X-ray structure of MCTI-II.
AB  - The high resolution crystallographic structure of MCTI-II complexed with beta
      trypsin (PDB entry 1MCT) was used to model the corresponding structures of the
      six inhibitor peptides belonging to Cucurbitaceae family (MCTI-I, LA-1, LA-2,
      CMTI-I, CMTI-III, CMTI-IV). Two model inhibitors, LA-1 and LA-2 were refined by
      molecular dynamics to estimate the average solution structure. The difference
      accessible surface area (DASA) study of the inhibitors with and without trypsin
      revealed the Arginine and other residues of the inhibitors which bind to trypsin.
      The hydration dynamics study of LA1 and LA2 also confirm the suitability of water
      molecules at the active Arg site. Moreover, the presence of a unique 3D
      structural motif comprises with the four CPRI residues from the amino terminal is
      thought to be conserved in all the six studied inhibitors, which seems essential
      for the directional fixation for proper complexation of the Arg (5) residue
      towards the trypsin S1-binding pocket. The role of the disulphide linkage in the
      geometrical stabilization of CPRI (Cysteine, Proline, Arginine, Isoleucine) motif
      has also been envisaged from the comparative higher intra molecular Cys (3) -Cys
      (20) disulphide dihedral energies.

PMID- 11245254
TI  - Interactions between mastoparan B and the membrane studied by 1H NMR
      spectroscopy.
AB  - Mastoparan B (MP-B) is an antimicrobial cationic tetradecapeptide amide isolated
      from the venom of the hornet Vespa basalis. NMR spectroscopy was used to study
      the membrane associated structures of MP-B in various model membrane systems such
      as 120 mM DPC micelles, 200 mM SDS micelles, and 3%(w/v) DMPC/DHPC (1:2)
      bicelles. In all systems, MP-B has an amphiphilic alpha-helical structure from
      Lys2 to Leu14. NOESY experiments performed on MP-B in nondeuterated SDS micelles
      show that protons in the indole ring of Trp9 are in close contact with methylene
      protons of SDS micelles. T1 relaxation data and NOE data revealed that the bound
      form of MP-B may be dominant in SDS micelles. The interactions between MP-B and
      zwitterionic DPC micelles were much weaker than those between MP-B and anionic
      SDS micelles. By substitution of Trp9 with Ala9, the pore-forming activity of MP
      B was decreased dramatically. All of these results imply that strong
      electrostatic interactions between the positively charged Lys residues in MP-B
      and the anionic phospholipid head groups must be the primary factor for MP-B
      binding to the cell membrane. Then, insertion of the indole ring of Trp9 into the
      membrane, as well as the amphiphilic alpha-helical structures of MP-B may allow
      MP-B to span the lipid bilayer through the C-terminal portion. These structural
      features are crucial for the potent antibiotic activities of MP-B.

PMID- 11245255
TI  - Artificial neural network model for predicting membrane protein types.
AB  - Membrane proteins can be classified among the following five types: (1) type I
      membrane protein. (2) type II membrane protein. (3) multipass transmembrane
      proteins. (4) lipid chain-anchored membrane proteins, and (5) GPI-anchored
      membrane proteins. T. Kohonen's self-organization model which is a typical neural
      network is applied for predicting the type of a given membrane protein based on
      its amino acid composition. As a result, the high rates of self-consistency
      (94.80%) and cross-validation (77.76%), and stronger fault-tolerant ability were
      obtained.

PMID- 11245256
TI  - Lipid induced conformation of the tachykinin peptide Kassinin.
AB  - Both the aqueous and lipid-induced structure of Kassinin, a dodecapeptide of
      amphibian origin, has been studied by two-dimensional proton nuclear magnetic
      resonance (2D 1H-NMR) spectroscopy and distance geometry calculations.
      Unambiguous NMR assignments of protons have been made with the aid of correlation
      spectroscopy (DQF-COSY and TOCSY) experiments and nuclear Overhauser effect
      spectroscopy (NOESY and ROESY) experiments. The distance constraints obtained
      from the NMR data have been utilized in a distance geometry algorithm to generate
      a family of structures, which have been refined using restrained energy
      minimization and dynamics. These data show that, while in water Kassinin prefers
      to be in an extended chain conformation, in the presence of perdeuterated
      dodecylphosphocholine (DPC) micelles, a membrane model system, helical
      conformation is induced in the central core and C-terminal region (K4-M12) of the
      peptide. N-terminus though less defined also displays some degree of order and a
      possible turn structure. The conformation adopted by Kassinin in the presence of
      DPC micelles is consistent with the structural motif typical of neurokinin-1
      selective agonists and with that reported for Eledoisin in hydrophobic
      environment.

PMID- 11245257
TI  - NMR and simulated annealing investigations of bradykinin in presence of
      polyphenols.
AB  - Epidemiological studies have shown that the incidence of some cardiovascular
      degenerative diseases appears to be lower in populations with regular but
      moderate drinking of red wine rich in polyphenols. One of the most important
      properties of polyphenols is to form complexes with proteins. The linear
      nonapeptide hormone bradykinin (H-Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9
      OH) is involved in a variety of physiological processes such as the
      cardiovascular processes. Thus, the goal of this work was to study the effects of
      tannins on the peptide structure by NMR investigations and molecular modeling.
      The results of these investigations show that in the presence of catechin, the
      peptide conformation is not affected and is in a random coil structure. On the
      contrary, the peptide structure is modified by the addition of dimeric
      proanthocyanidin B3 (catechin 4alpha-->8 catechin). The dimer leads to the
      formation of a large flexible turn between the 6-9 residues. Thus, the biological
      activities of bradykinin in the presence of polyphenols could be affected.

PMID- 11245258
TI  - GD1a in phospholipid bilayer: a molecular dynamics simulation.
AB  - Molecular dynamics simulation of ganglioside GD1a attached to the upper layer of
      a fully hydrated lipid bilayer of dimyristoyl phosphatidyl choline (DMPC) at room
      temperature under periodic boundary conditions was performed. The time average
      conformation of GD1a reveals that the terminal sialic acid is more exposed into
      the solvent than the internal branched one. Many interresidual contacts between N
      acetyl galactosamine-internal branched sialic acid; external Gal-external sialic
      acid; N-acetyl galactosamine-internal gal are also observed. The conformation of
      the GD1-hexasaccharide is stabilized by a number of intra molecular hydrogen
      bonds that were previously observed experimentally. The simulation results
      indicate that the presence of a single GD1a molecule has local effects on the
      bilayer. A local disorder in the arrangement of the acyl chains as well as the
      head groups is evident in the upper layer due to the presence of GD1a.

PMID- 11245260
TI  - Embryo development rates after transfer of oocytes matured in vivo, in vitro, or
      within oviducts of mares.
AB  - Objectives of the present study were to use oocyte transfer: 1) to compare the
      developmental ability of oocytes collected from ovaries of live mares with those
      collected from slaughterhouse ovaries; and 2) to compare the viability of oocytes
      matured in vivo, in vitro, or within the oviduct. Oocytes were collected by
      transvaginal, ultrasound-guided follicular aspiration (TVA) from live mares or
      from slicing slaughterhouse ovaries. Four groups of oocytes were transferred into
      the oviducts of recipients that were inseminated: 1) oocytes matured in vivo and
      collected by TVA from preovulatory follicles of estrous mares 32 to 36 h after
      administration of hCG; 2) immature oocytes collected from diestrous mares between
      5 and 10 d after aspiration/ovulation by TVA and matured in vitro for 36 to 38 h;
      3) immature oocytes collected from diestrous mares between 5 and 10 d after
      aspiration/ovulation by TVA and transferred into a recipient's oviduct <1 h after
      collection; and 4) im mature oocytes collected from slaughterhouse ovaries
      containing a corpus luteum and matured in vitro for 36 to 38 hours. Embryo
      development rates were higher (P < 0.001) for oocytes matured in vivo (82%) than
      for oocytes matured in vitro (9%) or within the oviduct (0%). However, neither
      the method of maturation nor the source of oocytes affected (P > 0.1) embryo
      development rates after the transfer of immature oocytes.

PMID- 11245259
TI  - Effects of beta-carotene, selenium and vitamin A on in vitro polymorphonuclear
      leukocytic activity in peripartal buffalo (Bubalus bubalus).
AB  - The effect of different concentrations of three antioxidans on phagocytic and
      kill activities of blood polymorphonuclear leukocytes (PMN) isolated from
      buffaloes during the peripartum period (4 weeks before to 7 weeks after
      parturition) was investigated in this study. Two concentrations of beta-carotene
      and vitamin A (10(-6) and 10(-5) M) and one concentration of Se (10(-9) M) were
      used. Phagocytic activity of PMN treated with beta-carotene (10(-6)M)
      significantly enhanced (P < 0.05) after parturition (Week 0 until Week 3),
      whereas the kill activity of the same cells significantly (P < 0.05) increased
      before and after parturition (at Weeks -4, -3, -2, 0, 1, 2 and 3). The
      concentration of beta-carotene (10(-5) M) enhanced phagocytosis of PMN only at
      Weeks 0 and 1 and kill activity at Weeks -4, -3, -2, 0, and 1. Selenium (10(-9)M)
      significantly (P < 0.05) enhanced phagocytic activity of PMN starting from
      parturition (Week 0) until Week 3 postpartum. Kill activity increased
      significantly both before (Weeks -4, -3 and -2) and after (Weeks 0, 1, 2, 3 and
      4) parturition. Vitamin A (10(-6) M) significantly enhanced phagocytic activity
      of PMN at Weeks 0, 1, and 2, whereas, the concentration of beta-carotene (10(-5)
      M) increased phagocytic activity only at Week 0. Kill activity of PMN increased
      significantly (P < 0.05) at Weeks -1 and 0 (10(-6)M). These results demonstrate
      that beta-carotene and selenium significantly enhanced phagocytic and kill
      activities of PMN isolated from buffaloes around parturition in vitro. Vitamin A
      enhanced phagocytosis and kill activities but not to the same extent as beta
      carotene and selenium. Apparently, the in vitro killing activity of PMN is a
      distinctive function from phagocytosis and both activities may be enhanced by the
      use of essential nutrients, especially during the peripartum period. Moreover,
      beta-carotene is more effective as an antioxidant than vitamin A in enhancing the
      activities of phagocytic cells.

PMID- 11245261
TI  - Characterization of semen collected from beagles and captive Japanese black bears
      (Ursus thibetanus japonicus).
AB  - This study characterized semen collected from the Japanese black bear, Ursus
      thibetanus aponicus, to provide information on semen cryopreservation for
      artificial breeding. Preliminary studies using a beagle dog as the model species
      showed that sperm concentration and total sperm count were lower in semen
      collected by electroejaculation than in semen collected by digital manipulation,
      but that sperm motility, viability and morphology were similar. Characterization
      of semen obtained from Japanese black bears by electroejaculation under general
      anesthesia revealed that semen volume and total number of spermatozoa collected
      were lower; but that sperm concentration, motility, viability and morphology were
      equivalent to those reported in other ursids. When semen was collected via a
      catheter inserted into the urethra during the stimulation for ejaculation, the
      sperm concentration, total sperm count and motility were relatively higher than
      when semen was collected directly in a test tube. Specific normal semen
      characteristics (mean +/- SEM) were pH, 7.6 +/- 0.0; volume, 0.212 +/- 0.038 mL;
      sperm concentration, 361 +/- 100 x 10(6)/mL; total sperm count, 84.0 +/- 32.2 x
      106; +++ motility, 30 +/- 5%; motility, 77 +/- 3%; viability 77 +/- 2%; and
      abnormal morphology, 11+/- 2%. These results suggest that semen can be collected
      from Japanese black bears by electroejaculation.

PMID- 11245262
TI  - Evaluation of the "Hamilton Thorn computer-based automated system" for dog semen
      analysis.
AB  - An objective evaluation of semen is warranted to assess the canine male fertility
      and to select appropriate techniques and extenders for semen preservation. With
      conventional microscopic evaluation, the subjectivity of the analysis makes any
      comparison of results difficult. In the present study, we validated the Hamilton
      Thorn computer-aided semen analyzer (HTR-IVOS10 analyzer) for objective
      assessment of canine semen. A description of fertile canine motility parameters
      using this analyzer is reported. Semen analysis at 38 degreesC is found to be
      more optimal and accurate than 30 degreesC. The Makler chamber was preferred to
      the Cell-vu, which induced a decrease of all semen motility parameters. The
      repeatability of the measures was good with intra-and inter-assay coefficients of
      variation below 10% and 20%, respectively, for most of measured parameters. An
      overestimation of semen concentration, increasing with dilution of semen, was
      observed when HTR-IVOS10 results were compared with the classical manual Makler
      cell evaluation. A significant decrease in semen motility parameters was recorded
      when high semen dilutions were used. Generated from the analysis of 42 mature
      fertile male beagle dogs, a description of semen motility parameters using the
      CASA system is presented to serve as reference when comparing Beagle ejaculates
      both in clinical and experimental studies.

PMID- 11245263
TI  - Quality control of refrigerated and cryopreserved semen using computer-assisted
      sperm analysis (CASA), viable staining and standardized fertilization in African
      catfish (Clarias gariepinus).
AB  - A new integrated approach including computer-assisted sperm analysis (CASA),
      viability staining and fertilization was used to study the quality of
      cryodiluents used in fish sperm cryopreservation. As an example the sperm quality
      of an African catfish, Clarias gariepinus (Burchell, 1822), was assessed by its
      fertilizing ability, motility and viability at day 0 (fresh), after 2 days'
      storage at 4 degreesC and after 2 days, 5 months and 10 months frozen at -196
      degreesC using solutions containing dimethyl sulphoxide (DMSO) or glycerol as
      permeating cryoprotectants. Four of the best freezing solutions were used,
      namely, Steyn's extender (S1, S4) and Mounib's extender (M3, M4) associating 10%
      hen's egg yolk. Progressive sperm movement measured by CASA and expressed by the
      straight line velocity (VSL), the average path velocity (VAP) and the curvilinear
      velocity (VCL) was highly correlated with hatching rates obtained from
      fertilization using minimal sperm:egg ratios. After 2 days, the motility of
      spermatozoa frozen with DMSO and 10% egg yolk had deteriorated less than that of
      spermatozoa stored at 4 degreesC. Post-thaw hatching rates reflected the post
      thaw sperm viability, which was cryodiluent dependent: 14.9+/-2.0% (S4), 17.0+/
      4.2% (S1), 25.9+/-3.7% (M4) and 52.1+/-3.4% (M3) after 5 months of
      cryopreservation. The percent motility of 10-months-frozen spermatozoa was high
      in M3 (70.7+/-11.4%) and M4 (64.0+/-2.0%) cryoprotected sperm when measured
      between 5 and 20 sec after activation, but decreased rapidly to 24.3+/-8.3% (M3)
      and 23.0+/-9.0% (M4) between 21 and 35 sec after activation. Mounib's extender
      (M3, M4) provided the best cryoprotection to the spermatozoa for all post-thaw
      sperm quality measurements and at all freezing durations. Sperm motility was
      positively related to fertility. Our method will make it possible to develop even
      better extenders and cryoprotectants.

PMID- 11245264
TI  - Reconstruction of the heteroparental diploid condition in rabbit zygotes by
      nuclear transfer.
AB  - Studies on genomic imprinting showed that parental genomes have complementary
      roles during embryogenesis, are both essential and need to be synchronized in
      their embryonic stage for successful development to term. To our knowledge, these
      studies have not been performed in species other than mice. We studied the in
      vitro and in vivo development of reconstructed zygotes by combining female
      haploid nuclear donors and androgenetic hemizygous recipients. Haploid donor
      embryos at the 8- or 32-cell stage were obtained from electroactivated young
      rabbit ova (eight pulses maximum, consisting of 0 6 kVcm(-1) for 60 microsec
      each, 38 min apart) which were further cultured for 24 h or 32 h. Couplets formed
      by both the haploid male hemizygous recipients and haploid female donor cells
      were electrofused (2.2 kVcm(-1) for 60 microsec duration each, 30 min apart) and
      their nuclear configuration determined 122 of those fused (43%: 122/286) were
      diploid. Reconstructed diploid zygotes developed in vitro up to the compacted
      morula, blastocyst and hatched stages (1/8-nuclei x 50%, 18% and 9% vs. 1/32
      nuclei: 47%, 25% and 19%; P > 0.05), respectively. In embryo transfer assays,
      both 1/32-reconstructed zygotes and control, non-manipulated zygotes were
      transferred to synchronized does Four live reconstructed fetuses (4/49: 8 1%
      survival rate) and five in regression stage (9/49: 18% implantation rate) were
      observed on Day 21 post-ovulation, whereas from control zygotes, 11 fetuses were
      alive (11/53 21% fetal survival rate) and 2 degenerated (13/53 x 24 5%
      implantation rate). Similar results were obtained from a final experiment, in
      which development was allowed to progress to term. Six live rabbit pups derived
      front experimentally reconstructed zygotes (11%; 6/54) and three fetuses in
      regression stage were obtained; values slightly lower than those derived from non
      manipulated and transferred control zygotes (18% 9/50, live born rate).

PMID- 11245265
TI  - Influence of Eqvalan (ivermectin) on quality and freezability of stallion semen.
AB  - The objective of this study was to evaluate the effect of Eqvalan (ivermectin) on
      stallion semen quality and freezability. Experiments were performed using 22
      Freiberger stallions, randomly divided into a control and test group. Semen was
      collected once a week for 17 weeks from October 1997 to February 1998. Eqvalan
      was given orally to all stallions of the test group at a therapeutic dose of 0.2
      mg ivermectin/kg. Besides measuring the scrotal width, ejaculates were collected
      to determine the volume, concentration, and the motility and morphology (normal
      sperm, major defects, vacuoles and acrosome defects). In addition, the motility
      and viability (fluorescence staining with propidium iodide/SYBR-14) were tested
      in all frozen-thawed semen samples. During the experimental period, stallions
      treated with Eqvalan had significantly better concentration (P < 0.0001) and
      motility (P < 0.0001) in fresh semen compared to control animals. After freezing
      thawing, the motility (P < 0.0001) and viability (P = 0.0003) of semen also
      increased significantly for treated stallions. Regarding morphology, normal sperm
      (P < 0.0001), major defects (P = 0.0027) and vacuoles (P = 0.0236) were
      significantly better in the Eqvalan group. In addition to group differences we
      also observed a time effect on morphological parameters as shown by a decrease of
      normal sperm and an increase of major defects in both groups during the
      experiment. Our results demonstrate that a single oral application of Eqvalan did
      not negatively influence the quality and freezability of stallion semen in the
      nonbreeding season. Rather, it seems that Eqvalan has a favorable effect on
      stallion fertility as most sperm parameters examined were significantly improved
      in treated animals compared to control.

PMID- 11245266
TI  - Effect of cooling of equine spermatozoa before freezing on post-thaw motility:
      preliminary results.
AB  - The ability to ship cooled stallion semen to a facility that specializes in
      cryopreservation of spermatozoa would permit stallions to remain at home while
      their semen is cryopreserved at facilities having the equipment and expertise to
      freeze the semen properly. To accomplish this goal, methods must be developed to
      freeze cooled shipped semen. Three experiments were conducted to determine the
      most appropriate spermatozoal extender, package, time of centrifugation,
      spermatozoal concentration and length of time after collection that spermatozoa
      can be cooled before cryopreservation. In the first experiment, spermatozoa were
      centrifuged to remove seminal plasma, resuspended in either a skim milk extender,
      a skim milk-egg yolk-sugar extender or a skim milk-egg yolk-salt extender, cooled
      to 5 degreesC and frozen in 0.5- or 2.5-mL straws either 2.5 or 24 h after
      cooling. Samples frozen 2.5 h after cooling had higher percentages of
      progressively motile (PM) spermatozoa (27%) than samples frozen 24 h after
      cooling (10%; P < 0.05). Samples frozen 2.5 h after cooling in skim milk
      extenders containing egg yolk had higher percentages of PM spermatozoa (average
      32%) than did spermatozoa frozen in extender containing skim milk alone (average
      16%; P < 0.05). The percentages of PM spermatozoa frozen in 0.5- or 2.5-mL straws
      were similar (21 and 28%, respectively; P > 0.05). In the second experiment,
      spermatozoa were centrifuged to remove seminal plasma either before (25 degreesC)
      or after cooling (5 degreesC), and spermatozoa were frozen after being cooled to
      5 degreesC for 2, 6, or 12 h. The percentages of PM spermatozoa were higher (P <
      0.05) for spermatozoa centrifuged before cooling (30%) than for spermatozoa
      centrifuged after cooling (19%). Spermatozoa centrifuged at 25 degreesC then
      cooled for 12 h to 5 degreesC had higher (P < 0.05) post-thaw progressive
      motility (23%) compared to spermatozoa cooled for 12 h and centrifuged at 5
      degreesC (13%). In the third experiment, spermatozoa were centrifuged for seminal
      plasma removal, resuspended at spermatozoal concentrations of 50,250 or 500 x
      10(6)/mL, cooled to 5 degreesC for 12 h and then frozen. Samples with spermatozoa
      packaged at 50 or 250 x 10(6)/mL had higher (P < 0.05 percentages of PM
      spermatozoa (25 and 23%) after freezing than did samples packaged at 500 x 10(6)
      spermatozoa/mL (17%). We recommend that semen be centrifuged at 25 degreesC to
      remove seminal plasma, suspended to 250 x 10(6) spermatozoa/ml and held at 5
      degreesC for 12 h prior to freezing.

PMID- 11245268
TI  - The effect of heparin on motility parameters and protein phosphorylation during
      bovine sperm capacitation.
AB  - It is generally accepted that incubation with heparin is required to induce
      capacitation of ejaculated bovine spermatozoa in vitro. The capacitation process
      implicates many biochemical events, and is correlated with modified sperm
      motility and the phosphorylation of specific proteins on tyrosine residues. To
      better understand the molecular basis of heparin-induced capacitation, bovine
      spermatozoa were incorporated with a radioactive substrate of protein kinases
      [gamma32P]-ATP, to observe protein phosphorylation dynamics over time. Sperm
      motion parameters including the percentage of motile spermatozoa, amplitude of
      lateral head displacement (ALH) and flagellar beat cross frequency (BCF) were
      assessed to determine whether the protein phosphorylation patterns induced by
      heparin also promote changes in motility. Capacitation was confirmed using the
      chlortetracycline fluorescence assay and the appearance of 'pattern B' stained
      spermatozoa. Evaluation of the different motility parameters during capacitation
      reveal that heparin has a marked negative effect, over time, on the percentage of
      motile spermatozoa, consistent with hyperactivation. Indeed, the presence of
      heparin greatly increases the BCF of bull spermatozoa and induces a significant
      increase in the ALH compared to spermatozoa incubated without heparin. We
      detected several sperm proteins that are phosphorylated over time. A 45 kDa
      protein is the most intensely phosphorylated of the sperm proteins. However, it
      is visible regardless of the presence of heparin. Interestingly, a second
      phosphorylated protein of approximately 50 kDa undergoes more intense
      phosphorylation with heparin than without. In summary, the present study
      demonstrated that heparin induces physiological changes in several sperm motility
      parameters including ALH, BCF and the percentage of motile spermatozoa. Heparin
      also increases the intensity of phosphorylation of a 50 kDa sperm protein. These
      results suggest that capacitation of bovine spermatozoa and capacitation
      associated motility changes may be regulated by a mechanism that includes protein
      phosphorylation, and that a presently unknown protein kinase is involved.

PMID- 11245267
TI  - Ovarian follicular development following administration of progesterone or
      aspiration of ovarian follicles in Holstein cows.
AB  - The objective of this study was to compare the effects of administration of a
      single injection of progesterone (P4) and follicle aspiration on Day 7 of the
      estrous cycle on the timing and synchrony of follicular wave emergence, time of
      ovulation, and concentrations of P4, estradiol and FSH in Holstein cows. Twenty
      cows were assigned to 4 groups (n=5 cows per group) in a 2 by 2 factorial
      arrangement. Cows were treated on Day 7 (Day 0 = estrus) of the estrous cycle
      with either sham follicular aspiration and an oil vehicle administered
      intramuscularly (control), aspiration of ovarian follicles (aspiration), 200 mg
      of P4 im, or aspiration and 200 mg of P4 im (aspiration + P4). On Day 11,
      PGF(2alpha)(25mg) was administered to all groups. Synchrony of ovulation was less
      variable in each of the treatment groups compared with the control group
      (P<0.05), whereas ovulation was delayed in cows in the P4 group (P<0.05). Day of
      follicular wave emergence was delayed in the cows of the P4 group compared with
      cows in the aspiration and aspiration + P4 groups (P<0.01), whereas variability
      in wave emergence was less among both groups of aspirated cows compared with the
      cows in the control group (P<0.01). More follicles 4 to 7 mm in diameter were
      detected in the 2 aspiration groups compared with the cows in the control and P4
      group (P<0.05). No difference was detected among groups in the maximum
      concentration of FSH associated with follicular wave emergence. We conclude that
      both the administration of P4 and the aspiration of follicles on Day 7 of the
      estrous cycle improves the synchrony of ovulation when luteolysis is induced on
      Day 11 and results in similar concentrations of FSH at the time of follicular
      wave emergence, but the timing of wave emergence and the number of follicles post
      emergence differ.

PMID- 11245269
TI  - Collection of tubal stage bovine embryos by means of endoscopy. A technique
      report.
AB  - Here we describe the development and optimization of endoscopy-mediated
      transvaginal access for collecting ova and embryos from the bovine oviduct. The
      novel technique was developed in three experimental setups: In Experiment 1
      embryos were collected unilaterally from nonstimulated heifers. We flushed the
      oviducts of superovulated heifers unilaterally (Experiment 2) and bilaterally
      (Experiment 3). In Experiment 1 the oviducts of 18 heifers were successfully
      cannulated, which resulted in the collection of twelve 1-cell to 8-cell embryos
      and one empty zona. Unilateral flushing of 13 animals (Experiment 2) resulted in
      84 ova with 6.3 +/- 3.2 observed ovulation sites. Bilateral flushing of 25
      animals (Experiment 3) resulted in 293 ova plus 10 empty zonae from 11.8 +/- 5.4
      ovulation sites. Given our experience from these studies we optimized the
      technical equipment by improving the flushing metal catheter (Experiment 4). The
      novel catheter hermetically sealed the lumen of the ampulla at the moment, the
      medium was flushed through the oviduct. This resulted in a visible flow of medium
      via oviducts toward the embryo filter connected to an embryo flushing catheter
      that was fixed in the uterine horns. Our endoscopy-guided method is minimally
      invasive and facilitates the flushing of tubal stage embryos.

PMID- 11245270
TI  - Vasculogenesis and angiogenesis as mechanisms of vascular network formation,
      growth and remodeling.
AB  - Two distinct mechanisms, vasculogenesis and angiogenesis implement the formation
      of the vascular network in the embryo. Vasculogenesis gives rise to the heart and
      the first primitive vascular plexus inside the embryo and in its surrounding
      membranes, as the yolk sac circulation. Angiogenesis is responsible for the
      remodeling and expansion of this network. While vasculogenesis refers to in situ
      differentiation and growth of blood vessels from mesodermal derived
      hemangioblasts, angiogenesis comprises two different mechanisms: endothelial
      sprouting and intussusceptive microvascular growth (IMG). The sprouting process
      is based on endothelial cell migration, proliferation and tube formation. IMG
      divides existing vessel lumens by formation and insertion of tissue folds and
      columns of interstitial tissue into the vessel lumen. The latter are termed
      interstitial or inter-vascular tissue structures (ITSs) and tissue pillars or
      posts. Intussusception also includes the establishment of new vessels by in situ
      loop formation in the wall of large veins. The molecular regulation of these
      distinct mechanisms is discussed in respect to the most important positive
      regulators, vascular endothelial growth factor (VEGF) and its receptors flk-1
      (KDR) and flt-1, the Angiopoietin/tie system and the ephrin-B/EpH-B system. The
      cellular mechanisms and the molecular regulation of angiogenesis in the
      pathological state are summarized and the differences of physiological and
      pathological angiogenesis elaborated.

PMID- 11245271
TI  - VEGF in brain tumors.
AB  - Vascular endothelial growth factor (VEGF) is a regulator of angiogenesis,
      vasculogenesis and vascular permeability. In this contribution, molecular and
      biological properties of VEGF are described. Furthermore, this article focuses on
      the evidence that angiogenesis in brain tumors is mediated by VEGF. Among the
      topics discussed are expression patterns of VEGF and its receptors in different
      brain tumors, possible regulatory mechanism involved in the VEGF-driven tumor
      angiogenesis and the involvement of VEGF in the genesis of peritumoral edema.
      Finally, anti-angiogenesis approaches to target VEGF/VEGF receptors are
      discussed.

PMID- 11245273
TI  - Nitric oxide and angiogenesis.
AB  - The steps required for new vessel growth are biologically complex and require
      coordinate regulation of contributing components, including modifications of cell
      -cell interactions, proliferation and migration of endothelial cells and matrix
      degradation. The observation that in vivo angiogenesis is accompanied by
      vasodilation, that many angiogenesis effectors possess vasodilating properties
      and that tumor vasculature is in a persistent state of vasodilation, support the
      existence of a molecular/biochemical link between vasodilation and angiogenesis.
      Several pieces of evidence converge in the indication of a role for nitric oxide
      (NO), the factor responsible for vasodilation, in physiological and pathological
      angiogenesis. Data originated in different labs indicate that NO can act both as
      an 'actor' of angiogenesis and as a 'director of angiogenesis', both functions
      being equally expressed during physiological and pathological processes. NO
      significantly contributes to the prosurvival/proangiogenic program of capillary
      endothelium by triggering and transducing cell growth and differentiation via
      endothelial-constitutive NO synthase (ec-NOS) activation, cyclic GMP (cGMP)
      elevation, mitogen activated kinase (MAPK) activation and fibroblast growth
      factor-2 (FGF-2) expression. Re-establishment of a balanced NO production in the
      central nervous system results in a reduction of cell damage during inflammatory
      and vascular diseases. Elevation of NOS activity in correlation with angiogenesis
      and tumor progression has been extensively reported in experimental and human
      tumors. In the brain, tumor expansion and edema formation are sensitive to NOS
      inhibition. On this basis, the nitric oxide pathway appears to be a promising
      target for consideration in pro- and anti-angiogenic therapeutic strategies. The
      use of NOS inhibitors seems appropriate to reduce edema, block angiogenesis and
      facilitate antitumor drug delivery.

PMID- 11245275
TI  - Descriptive analysis and quantification of angiogenesis in human brain tumors.
AB  - Quantitative determination of the degree of vascularity has been shown to be
      independently prognostically significant in many human tumor types. In
      particular, tumor vascularity has known importance in astrocytomas, in which
      endothelial proliferation is a criterion for anaplasia in many grading schemes.
      This review analyzes reports of microvessel quantification performed on
      histologic sections of human brain tumors, and in which correlations with
      clinical outcome, or other pathobiologic factors have been made. Among the
      conclusions are: (1) brain tumors have the unique feature of complex
      'glomeruloid' vessels, as well as heterogeneity of microvascular distribution and
      caliber; (2) lower-grade astrocytomas may incorporate pre-existing vessels, while
      glioblastomas may develop new vessels; (3) quantification may have additional
      independent prognostic value over and above routine histologic grade in low-grade
      astrocytomas with low tumor cell proliferative indices. These findings have
      implications for the appropriateness of antiangiogenic therapies.

PMID- 11245272
TI  - Growth factors in glioma angiogenesis: FGFs, PDGF, EGF, and TGFs.
AB  - It has become well accepted that solid tumors must create a vascular system for
      nutrient delivery and waste removal in order to grow appreciably. This process,
      angiogenesis, is critical to the progression of gliomas, with vascular changes
      accompanying the advancement of these tumors. The cascade of events in this
      process of blood vessel formation involves a complex interplay between tumor
      cells, endothelial cells, and their surrounding basement membranes in which
      enzymatic degradation of surrounding ground substance and subsequent endothelial
      cell migration, proliferation, and tube formation occurs. It is likely that a
      host of growth factors is responsible for mediating these key events. To date, a
      role for Vascular Endothelial Growth Factor (VEGF) in glioma angiogenesis has
      been convincingly demonstrated. This review explores the contribution of other
      growth factors--Fibroblast Growth Factors (FGFs), Platelet-Derived Growth Factor
      (PDGF), Epidermal Growth Factor (EGF), and Transforming Growth Factors (TGFs)--to
      glioma angiogenesis. These growth factors may influence glioma angiogenesis by
      directly stimulating endothelial cell proliferation, by mediating the expression
      of key proteases on endothelial cells necessary for angiogenesis, or by
      regulating the expression of VEGF and of each other.

PMID- 11245276
TI  - Physiology of angiogenesis.
AB  - Angiogenesis is a key prerequisite for growth in all vertebrate embryos and in
      many tumors. Rapid growth requires efficient transport of oxygen and metabolites.
      Hence, for a better understanding of tissue growth, biophysical properties of
      vascular systems, in addition to their molecular mechanisms, need to be
      investigated. The purpose of this article is twofold: (1) to discuss the
      biophysics of growing and perfused vascular systems in general, emphasizing non
      sprouting angiogenesis and remodeling of vascular plexuses; and (2) to report on
      cellular details of sprouting angiogenesis in the initially non-perfused
      embryonic brain and spinal cord. It is concluded that (1) evolutionary
      optimization of the circulatory system corresponds to highly conserved vascular
      patterns and angiogenetic mechanisms; (2) deterministic and random processes
      contribute to both extraembryonic and central nervous system vascularization; (3)
      endothelial cells interact with a variety of periendothelial cells during
      angiogenesis and remodeling; and that (4) mathematical models integrating
      molecular, morphological and biophysical expertise improve our understanding of
      normal and pathological angiogenesis and account for allometric relations.

PMID- 11245277
TI  - Angiogenesis, metastasis, and endogenous inhibition.
AB  - Angiogenesis and the development of metastases are intrinsically connected.
      Experimental data suggest that establishment and growth of metastases are
      influenced by soluble factors secreted from the originating solid tumor. Among
      these factors are so-called endogenous inhibitors of angiogenesis which keep
      metastasis in a non-proliferating quiescent state. For a number of tumors it has
      been shown that this dormant state is mediated through inhibition of
      angiogenesis. This dormant state is characterized by normal proliferation,
      increased apoptosis, and insufficient neo-vascularization. Removal of inhibiting
      anti-angiogenic factors led to growth of dormant metastases. A number of
      endogenous inhibitors have been identified and have shown success in experimental
      therapeutic trials. This might be of special interest for the treatment of
      cerebral metastases which are the most common type of malignant brain tumors.
      Similar to the spread of metastases, it is known that single glioma cells can be
      found in distant parts of the brain. While local recurrence is a common
      phenomenon in glioma, formation of clinical apparent distant metastasis occurs
      rarely. Several lines of evidence suggest that growth inhibition of remote glioma
      cells may be mediated by an endogenous inhibitory mechanism.

PMID- 11245274
TI  - Anti-angiogenic treatment strategies for malignant brain tumors.
AB  - The use of angiogenesis inhibitors may offer novel strategies in brain tumor
      therapy. In contrast to traditional cancer treatments that attack tumor cells
      directly, angiogenesis inhibitors target at the formation of tumor-feeding blood
      vessels that provide continuous supply of nutrients and oxygen. With respect to
      brain tumor therapy, inhibitors of angiogenesis display unique features that are
      unknown to conventional chemotherapeutic agents. The most important features are
      independence of the blood-brain barrier, cell type specificity, and reduced
      resistance. Malignant brain tumors, especially malignant gliomas, are among the
      most vascularized tumors known. Despite multimodal therapeutic approaches, the
      prognosis remains dismal. Thus, angiogenesis inhibitors may be highly effective
      drugs against these tumors. In a clinical setting, they could be applied in the
      treatment of multiple tumors or postsurgically as an adjuvant therapy to prevent
      recurrence. This article provides an overview of current anti-angiogenic
      treatment strategies with emphasis on substances already in clinical trials or
      candidate substances for clinical trials. The cellular and molecular basis of
      these substances is reviewed.

PMID- 11245278
TI  - Local anti-angiogenic brain tumor therapies.
AB  - The critical role of angiogenesis in the growth of solid tumors, including
      neoplasms of the central nervous system, has provided the impetus for research
      leading to the discovery of inhibitors of tumor neovascularization. The
      therapeutic potential of systemically administered antiangiogenic drugs for brain
      tumors, however, is limited by a variety of anatomic and physiologic barriers to
      drug delivery. Implantable controlled-release polymers for local drug
      administration directly into the tumor parenchyma have therefore been developed
      to achieve therapeutic concentrations of these drugs within the brain while
      minimizing systemic toxicity. With use of these polymers, successful
      antiangiogenic therapy for treatment of experimental intracranial malignancies
      has been achieved. This has been demonstrated with a variety of otherwise
      unrelated drugs -- including the angiostatic steroids, tetracycline derivatives,
      and amiloride -- which modulate collagenase activity, and thus, basement membrane
      and interstitial matrix metabolism. Controlled-release polymers provide a
      clinically practicable method of achieving sustained antiangiogenic therapy which
      can be readily used in combination with other treatment modalities such as
      cytoreductive surgery, radiation, and cytotoxic chemotherapy.

PMID- 11245279
TI  - Antiangiogenesis -- therapeutic strategies and clinical implications for brain
      tumors.
AB  - The poor prognosis of patients with malignant brain tumors in spite of aggressive
      multimodality therapy has led to the search for novel therapeutic strategies.
      Among the targets for such treatment approaches, tumor angiogenesis has captured
      the attention of not only the medical field but also of the lay public because of
      its conceptual departure from traditional methods of cancer therapy. Angiogenesis
      and vascular proliferation are particularly important in the growth and
      progression of malignant gliomas and are used as indicators of the degree of
      malignancy. Recent studies have helped us gain a better understanding of the
      molecular mediators of this process. It is now evident that after the initial
      formation of malignancy the continued growth of a glioma is critically dependent
      on its angiogenic potential. Hence, several approaches to control angiogenesis
      are being developed and tested. In the present review, we examine some of these
      approaches from a therapeutic perspective and summarize the findings from early
      human trials of such agents.

PMID- 11245280
TI  - Mathematical modelling of angiogenesis.
AB  - Angiogenesis, the formation of blood vessels from a pre-existing vasculature, is
      a process whereby capillary sprouts are formed in response to externally supplied
      chemical stimuli. The sprouts then grow and develop, driven initially by
      endothelial cell migration, and organize themselves into a branched, connected
      network. Subsequent cell proliferation near the sprout-tips permits further
      extension of the capillaries and ultimately completes the process. Angiogenesis
      occurs during embryogenesis, wound healing, arthritis and during the growth of
      solid tumours. In this article we first of all present a review of a variety of
      mathematical models which have been used to describe the formation of capillary
      networks and then focus on a specific recent model which uses novel mathematical
      modelling techniques to generate both two- and three-dimensional vascular
      structures. The modelling focusses on key events of angiogenesis such as the
      migratory response of endothelial cells to exogenous cytokines (tumour angiogenic
      factors, TAF) secreted by a solid tumour; endothelial cell proliferation;
      endothelial cell interactions with extracellular matrix macromolecules such as
      fibronectin; capillary sprout branching and anastomosis. Numerical simulations of
      the model, using parameter values based on experimental data, are presented and
      the theoretical structures generated by the model are compared with the
      morphology of actual capillary networks observed in in vivo experiments. A final
      conclusions section discusses the use of the mathematical model as a possible
      angiogenesis assay.

PMID- 11245281
TI  - Models for assessment of angiogenesis in gliomas.
AB  - In the last two decades, much attention has been focussed on mechanisms of glioma
      vascularization including the investigation of growth factors and receptors
      involved. Recently, these efforts resulted in various approaches for
      antiangiogenic treatment of experimental brain tumors. These basic science and
      preclinical trials need an assortment of models, which should allow investigating
      a variety of questions. Several objectives concerning basic endothelial cell (EC)
      characteristics can adequately be studied in vitro using EC monolayer assays.
      Three-dimensional spheroid techniques respect the more complex cell-cell and cell
      environment interplay within a three-dimensional culture. To optimize the
      imitation of the crucial interaction of human gliomas with host endothelial
      cells, immunological cells and extracellular matrix, animal models are mandatory.
      An essential rule is to utilize an orthotopic model, since tumor-host interaction
      is organ specific. To avoid alloimmunogenic responses, it is desirable to use
      weakly or not immunogenic glioma grafts, what is best accomplished in a syngeneic
      model. However, since rat gliomas poorly resemble human glioma growth patterns,
      human glioma xenografting into immunocompromized animals should be considered. In
      vivo monitoring techniques like videoscopy via a cranial window or magnetic
      resonance imaging (MRI) allow for functional studies and improve the validity of
      the model employed. Finally, it is essentially to recognize the limitations of
      each model considered and to select that model, which seems to be most
      appropriate for the objectives to be investigated.

PMID- 11245282
TI  - Molecular mechanisms of tumor angiogenesis and tumor progression.
AB  - The formation of new blood vessels (angiogenesis) is crucial for the growth and
      persistence of primary solid tumors and their metastases. Furthermore,
      angiogenesis is also required for metastatic dissemination, since an increase in
      vascular density will allow easier access of tumor cells to the circulation.
      Induction of angiogenesis precedes the formation of malignant tumors, and
      increased vascularization seems to correlate with the invasive properties of
      tumors and thus with the malignant tumor phenotype. In the last few years, the
      discovery and characterization of tumor-derived angiogenesis modulators greatly
      contributed to our understanding of how tumors regulate angiogenesis. However,
      although angiogenesis appears to be a rate-limiting event in tumor growth and
      metastatic dissemination, a direct connection between the induction of
      angiogenesis and the progression to tumor malignancy is less well understood. In
      this review, we discuss the most recent observations concerning the modulation of
      angiogenesis and their implications in tumor progression, as well as their
      potential impact on cancer therapy.

PMID- 11245284
TI  - Angiogenesis in transgenic models of multistep carcinogenesis.
AB  - The histopathology and the epidemiology of human cancers, as well as studies of
      animal models of tumorigenesis, have led to a widely accepted notion that
      multiple genetic and epigenetic changes have to accumulate for progression to
      malignancy. Formation of new blood vessels (tumor angiogenesis) has been
      recognized, in addition to proliferative capabilities and to the ability to down
      modulate cell death (apoptosis), as essential for the progressive growth and
      expansion of solid tumors beyond microscopic sizes of about 1-2 mm in diameter.
      Mice overexpressing activated forms of oncogenes or carrying targeted mutations
      in tumor suppressor genes have proven extremely useful for to linking the
      function of these genes with specific tumor processes; the interbreeding of these
      mice let us study the extent of cooperativity between different genetic lesions
      in disease progression, leading to a greater understanding of multi-stage nature
      of tumorigenesis.

PMID- 11245286
TI  - Tachyphylaxis and statin drugs.

PMID- 11245285
TI  - Vascular microenvironment in gliomas.
AB  - Structural and functional abnormalities of the vascular microenvironment
      determine pathophysiological characteristics of gliomas, such as loss of blood
      brain barrier function, tumor cell invasiveness, or permselectivity for large
      molecules. Moreover, the effectiveness of various therapeutic strategies
      critically depends upon the successful transvascular delivery of molecules. In
      order to shed more light on the vascular microenvironment in gliomas, a variety
      of experimental and clinical techniques have been applied to study the glioma
      microvasculature, including histology, vascular corrosion casts, microangiography
      by injection of dyes, blood flow measurements by autoradiography, tracer washout
      techniques, magnetic resonance imaging, as well as intravital fluorescence
      microscopy. This review summarizes the characteristic features of vascular
      morphology, angio-architecture, tumor perfusion, microvascular permeability, as
      well as microvessel-related immunological competence in gliomas. An improved
      understanding of the vascular microenvironment in gliomas will help in the future
      to optimize glioma imaging and delivery of vectors for gene therapy or
      encapsulated drug carriers in patients.

PMID- 11245287
TI  - Scientific theories and reality in gastric pathology.

PMID- 11245288
TI  - The vacuolating toxin of Helicobacter pylori: a few answers, many questions.

PMID- 11245283
TI  - Genes that regulate metastasis and angiogenesis.
AB  - Genetic instability and an accumulation of genetic and epigenetic changes during
      tumor progression lead to an increasingly aggressive and treatment-resistant
      phenotype, and ultimately metastasis. In recent years it has become well
      established that angiogenesis, the process by which new vasculature is formed
      from pre-existing vessels, is an essential component to primary tumor growth and
      distant metastasis. A greater understanding of the complex multitude of factors
      involved in tumor angiogenesis and metastasis is fundamental to the development
      of potential therapeutics to treat malignant disease. As highlighted throughout
      this review, angiogenesis and metastasis share many common cellular and molecular
      features. We will briefly discuss the pertinent genes involved in the regulation
      of angiogenesis and metastasis.

PMID- 11245289
TI  - Helicobacter pylori cagA and vacA types and gastric carcinoma.

PMID- 11245290
TI  - Cadherins and catenins in inflammation and oncogenesis.

PMID- 11245291
TI  - Gastric cancer with mutator phenotype: molecular bases and mechanisms of
      progression.

PMID- 11245292
TI  - Risk factors for cancer development in Helicobacter pylori gastritis.

PMID- 11245293
TI  - Diagnosis of Helicobacter pylori infection: which is the best test? The stool
      test.

PMID- 11245294
TI  - Diagnosis of Helicobacter pylori infection: which is the best test? The urea
      breath test.

PMID- 11245295
TI  - Helicobacter pylori and dyspepsia. Pro and against.

PMID- 11245296
TI  - Gastro-oesophageal reflux and Helicobacter pylori.

PMID- 11245297
TI  - Therapy and drug resistance in Helicobacter pylori infection.

PMID- 11245298
TI  - Helicobacter pylori and non-steroidal anti-inflammatory drugs.

PMID- 11245299
TI  - Helicobacter pylori-related extradigestive diseases and effects of eradication
      therapy.

PMID- 11245300
TI  - Helicobacter species in liver and biliary diseases.

PMID- 11245301
TI  - Mechanism underlying post-infectious motility disorders.

PMID- 11245302
TI  - Characterization of the motilin receptor, a member of a new receptor family.

PMID- 11245303
TI  - Ontogenesis of gastrointestinal motor function.

PMID- 11245304
TI  - Neurogastroenterology: evolving concepts and techniques to study motility and
      hypersensitivity.

PMID- 11245305
TI  - New Rome criteria for functional gastrointestinal disorders.

PMID- 11245306
TI  - Pathophysiology of gastro-oesophageal reflux: recent advances and therapeutic
      implications.

PMID- 11245307
TI  - Diagnosing gastro-oesophageal reflux: endoscopy, pH-metry or empirical trial?

PMID- 11245308
TI  - Chest pain and gastro-oesophageal reflux.

PMID- 11245309
TI  - New techniques for the detection of gastro-oesophageal reflux.

PMID- 11245310
TI  - Long-term therapy of gastro-oesophageal reflux disease: medical or surgical?

PMID- 11245311
TI  - Diabetes and the stomach.

PMID- 11245312
TI  - Functional dyspepsia: from motility to sensitivity.

PMID- 11245313
TI  - Dyspepsia responsive to acid suppression therapy: reflux disease or duodenal
      hypersensitivity?

PMID- 11245314
TI  - Diagnosing and treating dyspepsia. Current practice and new developments.

PMID- 11245315
TI  - Post-gastrectomy problems.

PMID- 11245316
TI  - Arthropod-borne spirochetoses: a historical perspective.

PMID- 11245317
TI  - Clinical aspects and prognostic factors in elderly patients hospitalised for
      community-acquired pneumonia.
AB  - The aims of this study were to determine the clinical and epidemiological
      characteristics of community-acquired pneumonia (CAP) in the elderly, to identify
      prognostic factors, and to establish a predictive model for mortality of CAP.
      Elderly patients with CAP admitted to "Carlos Haya" Hospital in Malaga, Spain,
      over a 36-month period were included. Multivariate analysis was used to identify
      prognostic factors from variables present on admission, from which a
      discrimination rule was constructed to predict mortality. A total of 343 patients
      were included, with the annual incidence ranging from 16.3 to 28.1 per 1,000
      admissions. Most (82.5%) had some kind of accompanying or underlying disease.
      Clinical presentation was atypical in 87 (25.4%). Microbiological diagnosis was
      made in 24.5%. There were 49 (14.3%) deaths. The prognostic factors in
      multivariate analysis on admission were bilateral radiographic infiltrate, a
      blood urea nitrogen level of more than 7 mmol/l, absence of fever, a respiratory
      rate of 30/min or more, confusion, and shock. The discriminating rule to predict
      mortality comprising three or more of these factors was 91.2% specific, with a
      negative predictive value of 93.4% and an overall accuracy of 86.9%. CAP in the
      elderly is associated with a high degree of mortality. The discriminating rule
      incorporating the prognostic factors identified is a powerful predictor of
      mortality.

PMID- 11245318
TI  - Factors compromising antibiotic activity against biofilms of Staphylococcus
      epidermidis.
AB  - Several factors associated with bacterial biofilms were studied for their role in
      phenotypic resistance to antibiotics. These factors included bacterial slime
      extracted from biofilms, reduced growth rates of biofilm-embedded bacteria and
      high bacterial inocula. Antibiotic activity against suspended bacteria in the
      presence of these factors, either alone or combined, was compared with activity
      against adherent biofilms. All MICs, determined by standard susceptibility tests,
      were below the sensitivity breakpoints for Staphylococcus epidermidis strain V2.
      The addition of bacterial slime to suspended bacteria reduced the bactericidal
      activity of glycopeptides but had less or no effect on the activity of the other
      antibiotics tested. High bacterial inocula affected the activity of
      flucloxacillin and quinolones only moderately or not at all, though a more
      pronounced effect on glycopeptides was observed. In contrast, the bactericidal
      activity of most antibiotics was severely compromised when adherent bacterial
      biofilms were used as inocula. In conclusion, the presence of slime, slow growth
      rates and high bacterial counts may explain the poor activity of glycopeptides
      against biofilm-embedded organisms, but these factors, either alone or in
      combination, do not explain the lack of bactericidal activity of other drugs
      against biofilms. Thus, additional factors need to be identified.

PMID- 11245319
TI  - Highly epidemic strains of methicillin-resistant Staphylococcus aureus not
      distinguished by capsule formation, protein A content or adherence to HEp-2
      cells.
AB  - In order to investigate whether highly epidemic methicillin-resistant
      Staphylococcus aureus (EMRSA) strains possess special properties that favour
      their dissemination and survival, a study was undertaken that examined
      methicillin-sensitive and methicillin-resistant strains of Staphylococcus aureus
      isolated in the UK. Included in the study were EMRSA types 1, 2, 3, 15 and 16.
      Phage types EMRSA-15 and -16, in particular, have emerged as significant hospital
      pathogens in the UK, resisting standard methods of control and spreading widely,
      while the incidence of other epidemic types has either declined or not changed.
      All of the strains included in the study were examined for capsule formation, the
      amount of bound protein A produced, and quantitative adherence to the human
      continuous epithelial cell line HEp-2. Although all of these properties varied
      amongst the strains examined, there was no relationship between any of them and
      methicillin resistance or epidemic type and, incidentally, no relationship
      between cell wall-bound protein A content and adherence.

PMID- 11245320
TI  - Comparison of two rapid colorimetric methods for determining resistance of
      mycobacterium tuberculosis to rifampin, isoniazid, and streptomycin in liquid
      medium.
AB  - The usefulness of two colorimetric methods for the determination of the
      susceptibility or resistance of Mycobacterium tuberculosis to rifampin,
      streptomycin, and isoniazid in liquid medium based on the reduction of 2,3-bis(2
      methoxy-4-nitro-5-sulfo-phenyl)-2H-tetrazolium-5-carboxanilide (XTT) and 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was investigated. The
      agar proportion method was used as the reference method. Results obtained
      indicate that the sensitivity of the XTT reduction assay for the detection of
      rifampin resistance was comparable to that observed, and previously described,
      for the MTT assay. However, the reduction of XTT yields a water-soluble formazan
      that can be easily quantified without performing additional steps such as
      addition of lysing buffer and solubilization. Furthermore, the colorimetric
      assays, based on the reduction of XTT and MTT for the detection of isoniazid and
      streptomycin resistance in Mycobacterium tuberculosis, were standardized. The
      inhibition of MTT and

PMID- 11245321
TI  - Randomized trial of cefotiam prophylaxis in the prevention of postoperative
      infectious morbidity after elective cesarean section.
AB  - A prospective, randomized study was performed in order to evaluate the effect of
      cefotiam in the prevention of postoperative infectious morbidity in patients
      undergoing low-risk elective cesarean section. A total of 146 patients were
      randomly assigned to receive either intraoperative single-shot prophylaxis with 2
      g cefotiam (study group, n =76) or no prophylaxis (control group, n=70). Due to a
      higher rate of urinary tract infections, the incidence of infectious morbidity
      after cefotiam prophylaxis was higher in the study group than in the control
      group (16% vs. 9%, P=0.1). Postoperative infectious morbidity following low-risk
      elective cesarean section cannot be reduced by intraoperative cefotiam
      prophylaxis.

PMID- 11245322
TI  - Parovirus B19 infection in an HIV-infected patient with febrile pancytopenia and
      acute hepatitis.
AB  - The case of a 34-year-old male patient with HIV infection referred for severe
      febrile pancytopenia is reported. Clinical and laboratory evaluations revealed
      acute hepatitis B infection and concomitant parvovirus B19 infection. The patient
      died just before treatment with immune globulin was to be administered.
      Parvovirus B19 has been found to cause a wide variety of hematologic disorders
      such as neutropenia, thrombocytopenia, pancytopenia, and hemophagocytic syndrome.
      The role of parvovirus B19 in the pathogenesis of bone marrow or liver
      involvement is briefly discussed.

PMID- 11245323
TI  - HIV-1 plasma viremia not increased in patients receiving highly active
      antiretroviral therapy after influenza vaccination.
AB  - The effect of vaccinating patients with sustained undetectable HIV-1 viremia (VL)
      achieved with highly active antiretroviral therapy was prospectively
      investigated. During the 1998 influenza immunization period, 39 HIV-1-infected
      patients who showed a VL<20 copies/ml for at least 6 months before the study
      entry date were vaccinated for influenza. Twenty-two vaccinees were immunized at
      entry. Seventeen controls were followed for 4 weeks after entry, crossing over
      then to the vaccination group. The proportion of patients with undetectable VL
      was not significantly different between the vaccination and control groups 2 and
      4 weeks after entry. Therefore, influenza immunization of patients with
      undetectable viremia achieved with highly active antiretroviral therapy does not
      seem to affect VL.

PMID- 11245324
TI  - Tricuspid valve endocarditis in adult patients without known predisposing
      factors.
AB  - Four patients with no known predisposing conditions developed tricuspid valve
      endocarditis. All patients had community-acquired infection with a rapidly
      progressive course that was complicated by right heart failure and respiratory
      insufficiency. Pulmonary involvement was prominent in all cases. The infectious
      process was due to Staphylococcus aureus in three patients and to Streptococcus
      intermedius in one patient. Three patients underwent early surgical intervention;
      the outcome was favourable in all cases. It is clear that tricuspid valve
      endocarditis can occur in the absence of known predisposing factors, and when
      Staphylococcus aureus is involved, the course of the disease may be acute and
      rapidly progressive.

PMID- 11245325
TI  - Emerging erythromycin resistance among group B streptococci in Korea.
AB  - In order to determine possible trends in the susceptibility and distribution of
      group B streptococci (GBS) serotypes in a Korean population and to elucidate any
      relationship between the serotypes and the antimicrobial susceptibility patterns
      found, 185 clinical isolates of GBS were investigated between 1990 and 1998. The
      rate of erythromycin resistance increased from 0% during the period 1990-1995 to
      26% in 1996 and 40% in 1998. The overall rates of resistance to erythromycin and
      clindamycin were 20% and 22.2%, respectively. GBS serotype V was not detected
      until 1995, but it was isolated in 1996 and ranked third in frequency (18.8%) in
      1997. Among the 37 erythromycin-resistant strains detected, 54.1% and 29.7% were
      of serotype III and V, respectively. The emerging erythromycin resistance
      detected among these GBS isolates was mainly due to a sudden increase in the
      incidence of GBS serotypes with multidrug-resistant phenotypes.

PMID- 11245326
TI  - Antibiotic susceptibilities among recent clinical isolates of Haemophilus
      influenzae and Moraxella catarrhalis from fifteen countries.
AB  - Between July 1998 and July 1999, 3,060 Haemophilus influenzae and 1,486 Moraxella
      catarrhalis strains were isolated in 31 centers in 15 countries in order to
      determine their antimicrobial susceptibilities and the presence of beta-lactamase
      production in Haemophilus influenzae. Overall 17.1% of the Haemophilus influenzae
      isolates were beta-lactamase positive, while more than 95% were susceptible to
      amoxicillin/clavulanate, cefaclor, loracarbef, cefuroxime, azithromycin and
      ciprofloxacin. Eleven (0.3%) isolates were beta-lactamase positive and ampicillin
      resistant and 7 (0.2%) isolates were ciprofloxacin resistant. The minimum
      inhibitory concentrations for 90% of the isolates tested were lowest for
      ciprofloxacin (0.03) and highest for cefprozil (8) against Moraxella catarrhalis.

PMID- 11245327
TI  - Aspects of Lyme borreliosis in Europe.
AB  - Lyme borreliosis in Europe is somewhat different from that encountered in the
      USA. The aim of this review is to present historical, ecological,
      epidemiological, clinical, and therapeutic aspects associated with Lyme
      borreliosis in Europe. It becomes apparent that a considerable body of
      information about European Lyme borreliosis exists, which has been accumulated
      for more than 100 years.

PMID- 11245328
TI  - Clonal relationships among penicillin-susceptible, multiresistant serotype 6B
      Streptococcus pneumoniae isolates recovered in Greece and France.
AB  - In January 1996 the emergence of penicillin-susceptible, multiresistant serotype
      6B Streptococcus pneumoniae isolates resistant to chloramphenicol, tetracycline,
      erythromycin, clindamycin and trimethoprim-sulfamethoxazole was observed in young
      carriers in the city of Patras, located in the southwestern region of Greece.
      Later, a significant spread of pneumococci with this unusual phenotype was noted
      in carriers living in various other areas of the country. Using restriction
      fragment length polymorphism of the ribosomal RNA genes, clonal relationships
      were found between these Greek strains and serotype 6B penicillin-susceptible,
      multiresistant pneumococci isolated in France between January 1992 and September
      1996. The French and Greek isolates appear to have a common ancestry.

PMID- 11245330
TI  - Saliva samples not a reliable tool for diagnosis of Helicobacter pylori
      infection.

PMID- 11245329
TI  - Relationship of Ureaplasma urealyticum biovars to the presence or absence of
      bacterial vaginosis in pregnant women and to the time of delivery.
AB  - In a nested case-control study, the occurrence of Ureaplasma urealyticum in
      cervical specimens from 84 women with idiopathic preterm delivery and from 400
      women delivering at term was investigated. The two potential risk factors for
      preterm delivery, colonization with Ureaplasma urealyticum and bacterial
      vaginosis, were found to be interdependent variables. The association between
      these factors and preterm delivery was assessed by regression analysis. Neither
      colonization with Ureaplasma urealyticum (odds ratio [OR] 0.7, 95% confidence
      interval [CI] 0.4-1.2) nor bacterial vaginosis (OR 0.8, 95% CI 0.3-1.8) was
      associated with preterm delivery. In women who delivered preterm, biovar 2 was
      found significantly more often in those with the clinical diagnosis of bacterial
      vaginosis (43%) than in those without (5%) (OR 15, 95% CI 1.2-209).

PMID- 11245331
TI  - Emergence of group A beta-hemolytic streptococci resistant to erythromycin in
      Athens, Greece.

PMID- 11245332
TI  - Changing patterns in the etiology of HIV-associated bacterial pneumonia in the
      era of highly active antiretroviral therapy.

PMID- 11245333
TI  - Comparative activities of isepamicin, amikacin, cefepime, and ciprofloxacin alone
      or in combination with other antibiotics against Stenotrophomonas maltophilia.

PMID- 11245334
TI  - Macronutrient intake and estrogen metabolism in healthy postmenopausal women.
AB  - The purpose of this study was to determine if dietary factors could bias
      estimates of the relationships between estrogen metabolites and breast cancer
      risk factors. A lower ratio of urinary 2-hydroxyestrone/16alpha-hydroxyestrone
      (2/16) has been associated with breast cancer diagnosis. However, both estrogen
      metabolism and breast cancer risk have been associated with dietary intake, and
      breast cancer patients may have different dietary patterns than healthy controls.
      An association between urinary 2/16 levels and breast cancer risk may be due to
      transitory dietary change after diagnosis, or due to other breast cancer risk
      factors which have been associated to steroid hormone metabolism. Thirty-seven
      healthy postmenopausal women provided two 24-h urine samples at a two-week
      interval. Six 24-h diet recalls were administered in this same time period. In
      linear regression analysis, dietary fat-to-fiber ratio (fat/fiber) and the
      saturated fat/soluble fiber ratio was inversely associated with urinary 2/16
      values (b = -0.22, 95% CI (-0.43, -0.01); b= -0.26, 95% CI (-0.43, -0.09),
      respectively). The effects of these dietary factors on 2/16 were independent of
      body mass index or other breast cancer risk factors. These study results suggest
      that some of the variation in estrogen metabolite levels among postmenopausal
      Caucasian women may be due to dietary intake, and that dietary factors should be
      carefully measured and evaluated when investigating the relationship between
      estrogen metabolites and breast cancer risk.

PMID- 11245335
TI  - Downregulation of gelsolin correlates with the progression to breast carcinoma.
AB  - The actin cytoskeleton underlies several normal cellular functions and is
      deranged during carcinogenesis. Gelsolin, a multifunctional actin-binding
      protein, is downregulated in several types of tumors and its abnormal expression
      is one of the most common defects noted in invasive breast carcinoma (ICA). This
      study utilizes immunohistochemistry to examine the expression of gelsolin in 95
      ICA, 59 ductal carcinoma in situ (DCIS) and 36 benign lesions, including 17
      atypical ductal hyperplasia (ADH). Cytoplasmic staining was scored as positive,
      reduced or negative. Gelsolin expression was then correlated with patient's age,
      tumor size, histologic grade and lymph node status. All unremarkable breast
      biopsies, 88% of ADH, 44% of DCIS and 28% of ICA were positive for gelsolin. This
      represents a significant difference among the groups (p = < 0.0001) and the trend
      towards reduced gelsolin with the progression to ICA is significantly linear (p =
      < 0.0001). For invasive carcinoma, patients older than 44 years were
      significantly more likely to have decreased expression of gelsolin than patients
      44 years old and younger (p = 0.007). Bivariate analysis showed no correlation of
      gelsolin expression with lymph node status (p = 0.62), tumor size (p = 0.10),
      histologic grade (p = 0.42), estrogen receptor status (p = 1.0) or other
      clinicopathologic parameters. In clinical follow-up, there were 18 breast tumor
      related deaths within a median follow-up time of 4.2 years. Survival analysis
      indicated that the level of gelsolin expression may be associated with survival
      (p = 0.06). In summary, the frequency of gelsolin deficiency increases
      significantly with progression from ADH to DCIS to ICA. Additionally, gelsolin
      expression may be an independent marker of prognosis.

PMID- 11245336
TI  - Expression of CD44 isoforms in infiltrating lobular carcinoma of the breast.
AB  - Expression of CD44 has been shown to correlate with the progression and prognosis
      of some malignant tumors. The aim of this study was to evaluate the expression of
      CD44 isoforms in infiltrating lobular carcinomas and analyse their potential as
      prognostic indicators. A panel of 39 tumors were examined for their expression of
      membranous and cytoplasmic CD44s, v3, v5, v6, v7 and v3-10 in the infiltrating
      cells, by immunohistochemical staining. The protein positive tumors showed
      membranous and/or cytoplasmic staining with all antibodies used except for
      CD44v7, which only displayed cytoplasmic staining. Cytoplasmic expression of
      CD44v3 (P = 0.014) and membranous expression of v6 (P = 0.039) were significantly
      associated with alveolar, classical/alveolar carcinomas and mucinous/alveolar
      carcinomas. Furthermore, in alveolar, classical/alveolar and mucinous/alveolar
      carcinomas, cytoplasmic staining of CD44v5 was correlated with lymph node
      negative patients (P = 0.048), whereas membranous v5 was correlated with lymph
      positive patients (P = 0.048). In classical, classical/trabecular and trabecular
      carcinomas expression of membranous CD44s was significantly correlated with lymph
      node status (P = 0.042).

PMID- 11245337
TI  - Retinoid receptors in human breast carcinoma: possible modulators of in situ
      estrogen metabolism.
AB  - Retinoid receptors (retinoic acid (RARs) and retinoid X (RXRs) receptors) were
      immunolocalized in 32 human invasive ductal breast carcinomas. These findings
      were correlated with clinicopathological parameters to study their biological
      significance in breast carcinoma. Retinoid receptor immunoreactivity, except for
      RXRgamma, was detected in the nuclei of carcinoma cells. Percentage of positive
      cases were RARalpha; 81%, RARbeta; 6%, RARgamma; 28%, RXRalpha; 81%, and RXRbeta;
      59%. A significant correlation was detected between RARalpha labeling index (LI),
      and RXRalpha LI (r = 0.667, p < 0.001). Results from immunoblotting performed in
      three cases were consistent with those of immunohistochemistry. There was a
      significant correlation between RARalpha LI and 17beta-hydroxysteroid
      dehydrogenase (17beta-HSD) type 1 immunoreactivity (p < 0.05). A significant
      correlation was also detected between RARalpha (r= 0.413, p = 0.019) or RXRalpha
      (r = 0.429, p = 0.014) LI, and estrogen receptor (ER) LI. In T-47D breast cancer
      cells, which express RARalpha, RXRalpha and ER, 17beta-HSD reductive activity
      increased 1.76-fold (p < 0.001), five days following treatment with 10 nM
      retinoic acid. These data suggest that retinoid receptors modulate various
      effects of retinoids, including estrogen metabolism in human breast carcinomas.

PMID- 11245338
TI  - Tamoxifen suppresses histologic progression to atypia and DCIS in MCFIOAT
      xenografts, a model of early human breast cancer.
AB  - We evaluated the effects of tamoxifen on the growth and progression of MCFIOAT
      xenografts, an estrogen responsive model of human breast tumor progression, in
      which cells are injected orthotopically into the mammary fat pad of female nude
      mice. At 10 weeks following implantation, histologic sections of each graft were
      evaluated microscopically for histologic lesions analogous to human breast tumor
      progression, graded as simple hyperplasia, complex hyperplasia, atypical
      hyperplasia, ductal carcinoma in situ and invasive carcinoma. Three out of five
      xenografts in (endocrine intact) control animals progressed to atypical
      hyperplasia, one progressed to ductal carcinoma in situ and one to invasive
      carcinoma. The latter two control grafts also contained foci of putative
      precursor lesions (i.e. atypical hyperplasia and in situ carcinoma,
      respectively). Tamoxifen supplemented xenografts (N= 17) were uniformly smaller
      than controls, but contained invasive carcinoma in a similar proportion (4/17,
      24%). However, none of these grafts exhibited ductal carcinoma in situ and only
      one contained atypical hyperplasia. Most grafts in tamoxifen supplemented animals
      (10/17, including all four with carcinomas) showed complex hyperplasia, which
      typically dominated the graft. We conclude that tamoxifen selectively inhibits
      the appearance or growth of preinvasive index lesions. Development of malignancy
      in the absence of such precursors, though, implies selection for alternative
      histogenetic pathways as a result of endocrine manipulation.

PMID- 11245339
TI  - Detection of VIP receptors in MNU-induced breast cancer in rats: implications for
      breast cancer targeting.
AB  - Vasoactive intestinal peptide (VIP) is a 28 amino acid neuropeptide with a wide
      range of biological activities. Receptors for VIP (VIP-R) are overexpressed in
      breast cancer, where they may have diagnostic and therapeutic implications.
      Although N-methyl nitrosourea (MNU)-induced breast cancer in rats is used
      extensively as a model to study mammary carcinogenesis, there is no information
      about the expression of VIP-R in this model. Therefore, the purpose of this study
      was to investigate the presence of VIP-R in MNU-induced breast cancer in rats so
      that this model can be used to perform studies involving VIP-R. Breast cancer was
      induced in 36-day-old virgin female Sprague-Dawley rats, by a single intravenous
      injection of MNU (50 mg/kg body weight). The breast tumors were detected 100-150
      days after injection. The normal and cancerous rat breast tissue were excised and
      20 micro sections were incubated with 40 nM fluorescein-labeled VIP (Fluo
      VIP(TM)), in the presence and absence of 1000-fold excess unlabeled VIP,
      pituitary adenylate cyclase activating polypeptide (PACAP) or secretin. The
      sections were visualized under a fluorescence microscope and photographed. Fluo
      VIP(TM) stained rat breast cancer tissue homogeneously and to a much greater
      extent than normal rat breast tissue (p < 0.05). This staining was specific as
      indicated by displacement of Fluo-VIP(TM) by excess unlabeled VIP and PACAP.
      Displacement of Fluo-VIP(TM) by secretin indicated the probable presence of VIP
      receptors of type VPAC1 (VIP receptor subtype 1) in the rat breast. These data
      suggest that, as in human breast cancer, VIP-R, predominantly of type VPAC1, are
      overexpressed in MNU-induced rat breast cancer tissue as compared to the normal
      rat breast tissue. Thus, MNU-induced rat breast cancer model can be used as a
      tool to study the functional role of VIP-R in human mammary carcinogenesis and
      VIP-R mediated active breast cancer targeting. This could have implications in
      the diagnosis, prognosis and therapy of human breast cancer.

PMID- 11245340
TI  - Matrix metalloproteinase-2 (MMP-2) is associated with the risk for a relapse in
      postmenopausal patients with node-positive breast carcinoma treated with
      antiestrogen adjuvant therapy.
AB  - Node-positive breast carcinoma is an aggressive disease. Postmenopausal patients
      benefit from antiestrogen adjuvant therapy. Predictive markers could, however, be
      useful in selecting these patients for different modalities of adjuvant therapy.
      Recently, we showed that MMP-2 (72 kD type IV collagenase/gelatinase A) is
      correlated with unfavorable prognosis in premenopausal breast carcinoma patients.
      Expression of the immunoreactive protein for MMP-2 was evaluated prospectively in
      this study in paraffin tissue sections from primary tumors of 100 postmenopausal,
      node-positive breast carcinoma patients treated with an adjuvant antiestrogen
      therapy. A specific MMP-2 monoclonal antibody in an avidin-biotin
      immunohistochemical staining was used. Sixty nine percent of the samples were MMP
      2 positive. Eighty three percent of the MMP-2 negative patients lived for 5 years
      without a recurrence, while only 67% of the patients with an MMP-2 positive
      primary tumor were recurrence-free at that time (p < 0.05; log rank analysis).
      MMP-2 positivity showed a significant correlation with shortened survival in
      patients with a small primary tumor (T1-2) and a low axillary tumor burden. One
      hundred percent of these patients with an MMP-2 negative breast carcinoma
      survived for 5 years, compared to 73% of the MMP-2 positive cases alive at that
      time (p = 0.02). In conclusion, we show here that MMP-2 is a prognostic indicator
      in postmenopausal patients with node-positive breast carcinoma with a low tumor
      burden, and that it predicts a risk for failure in antiestrogen adjuvant therapy.
      It might have predictive value in selecting the most efficient adjuvant therapy
      in this set of patients.

PMID- 11245341
TI  - The effect of patient reminders on the use of screening mammography in an urban
      health department primary care setting.
AB  - Mammography screening continues to be under-utilized, especially among women from
      lower socioeconomic groups. In order to determine whether having direct access to
      health care services has an effect on mammography use among low income women, we
      conducted a randomized trial of two alternative letter reminders among 1,717
      women who were enrolled at two locations of a multi-site inner city health
      department in Detroit. All participants were 39(1/2) years of age and older and
      were due for a screening mammogram at randomization. A physician-directed
      reminder form was placed in each of the participant's medical records at the
      beginning of the study. In addition participants were randomized to receive
      either a letter directing them to visit their primary care physician, a letter
      directing them to contact the clinic directly to schedule a mammogram, or no
      letter. Study participants were predominantly African-American, two-thirds of
      whom were over age 50, and who had minimal health insurance coverage. During the
      intervention year, mammograms were completed by 179 out of 967 study women at
      site one (18.5%), and 90 out of 750 study women at site two (12%). A multivariate
      model controlling for the simultaneous effect of age, insurance type, visit
      history and past mammography use, showed no significant independent effect of
      either type of letter reminder on mammography completion during the study year.
      In conclusion, letters targeted at women due for screening mammograms did not
      have a beneficial effect on mammography utilization above and beyond that of a
      physician medical record reminder.

PMID- 11245342
TI  - Angiogenesis sustains tumor dormancy in patients with breast cancer treated with
      adjuvant chemotherapy.
AB  - Experimental studies performed in Folkman laboratories suggest that angiogenesis
      is involved in the biology of tumor dormancy. We determined the vascular index in
      a series of 190 women operated of node-positive invasive breast cancer treated
      with adjuvant chemotherapy (CMF schedule) and we studied the relationship between
      vascularity of primary tumors with the behaviour in time of metastasis. The study
      of the hazard function of recurrence (in any site) was performed resorting to a
      generalized linear modelling approach with a binominal error according to Efron.
      A total of 80 cases developed recurrences during the period of observation. We
      found that the hazard function of metastasis in time presented two peaks of
      incidence at 20 and 60 months, respectively. We also plotted the curves of the
      hazard function by considering three values of microvessel counts corresponding
      to the quartiles of their distribution. The risk of first recurrence was
      associated with vascular index, and the patients of the third quartile of
      distribution of microvessels had the highest risk. In the final full model for
      the risk of recurrence at 5 years vascular index provided the highest prognostic
      contribution followed by the number of involved axillary lymph nodes. The
      observation that the patients with highly angiogenic tumors are at high risk of
      recurrence coupled with the identification of the second peak of incidence after
      5 years which was also mainly sustained by angiogenic tumors suggest that a
      fraction of breast cancers promote metastasis after a period of tumor dormancy.
      The clinical and therapeutic implications of our results are discussed.

PMID- 11245343
TI  - Prognostic evaluation of proliferative activity and DNA content in the phyllodes
      tumor of the breast: immunohistochemical and flow cytometric study of 118 cases.
AB  - The goal of this study was the prognostic evaluation of histology, mitotic rate,
      S-phase fraction (SPF) and expression of proliferative antigen Ki67 and p53
      protein in phyllodes tumor of the breast. The study was performed in the group of
      118 patients with phyllodes tumor treated by surgery from 1952 to 1998. Mitotic
      rate was assessed on the representative histological specimens. Expressions of
      Ki67 and p53 were evaluated by immunohistochemistry on a section from the
      corresponding paraffin blocks which were also used for flow cytometric DNA
      evaluation. Histologically, 52 tumors were benign (LGM), 24 borderline
      malignancies (BM) while among 42 malignant tumors, 20 were monomorphous (HGM) and
      the remaining 22 revealed heterologic elements (HGH). Tumor recurrencies occurred
      in 17 patients, predominantly during the first three years after surgery, and 13
      patients died of the tumor (1 BM, 12 both malignant variants). Multivariate
      analysis demonstrated mitotic rate, SPF and p53 expression as independent
      prognostic parameters for the disease-free survival. Histological tumor type and
      expression of Ki67 influenced independently the overall survival. In conclusion,
      the histological type of tumor phyllodes forms the basis for the prognosis of
      clinical outcome, but the indicators of the proliferative activity, especially
      Ki67 index, are valuable prognostic factors among patients with malignant variant
      of phyllodes tumor of the breast. Expression of the p53 protein in tumor cells
      could be also useful when the percentage of cells and intensity of expression are
      considered.

PMID- 11245345
TI  - Low birthweight at a Papua New Guinea highlands hospital.
AB  - A prospective case-control study involving 75 low birthweight (LBW) babies and
      224 controls was carried out at the Mount Hagen General Hospital over a period of
      7 months, from June to December 1997. Identified risk factors for LBW in this
      population included maternal age (age less than 22 years or over 35 years, p =
      0.03), a birth interval of less than 2 years (p = 0.006), no antenatal booking (p
      = <0.005), low attendance at antenatal clinic (p = <0.005), fever during
      pregnancy (p = <0.005), PET (p = 0.05), APH (p = <0.015), and maternal smoking
      during pregnancy (p = 0.008). Other well-established risk factors for LBW, i.e.
      small stature, low body mass index (BMI), haemoglobin less than 8 g/dl, and low
      educational attainment, appeared to be more frequent in the mothers of the LBW
      babies than the controls but differences did not reach statistical significance.
      The results suggest the need for improved provision of, and efforts to increase
      the use of, antenatal and family planning services. The results also provide
      clear evidence of the deleterious effects of smoking during pregnancy in a
      developing country.

PMID- 11245344
TI  - Influence of consanguinity and IgE receptor genotypes on clinical manifestations
      of asthma in Kuwaiti children.
AB  - An association between IgE receptor FcepsilonRIbeta polymorphism and atopy has
      been reported and proposed to be maternally transmitted. In a previous
      communication we reported high prevalence of the IgE receptor FcepsilonRIbeta
      variant (Leu 181/Leu 183) in Kuwaiti Arabs with asthma. This study investigates
      the association of this variant with parental consanguinity, maternal vs paternal
      inheritance, gender, and severity of asthma in 52 Kuwaiti families in whom at
      least one person had asthma. Using an allele refractory mutation screening (ARMS)
      test, blood (from 212 subjects, including asthmatic children, their parents and
      siblings) was tested for the presence of the normal and variant sequence of the
      IgE receptor FcepsilonRIbeta [homozygous normal sequence (Ile 181/Val 183, NN),
      the variant sequence (Leu 181/Leu 183, LL) and the heterozygous state NL]. In the
      52 families 99 subjects were asthmatic. The consanguinity rate was 42 per cent
      which is similar to the 54 per cent reported for the Kuwaiti population as a
      whole. There were slightly more asthmatic fathers (27 per cent) than mothers (21
      per cent) but this difference is not significant. The male to female ratio
      amongst the asthmatics was 1.5:1 and there was no gender effect on the frequency
      of the homozygous variant. Fifty-eight subjects (59 per cent) had severe and 41
      (41 per cent) moderate asthma. Significantly more patients with severe asthma (58
      per cent) were homozygous for the variant (Leu 181/Leu 183) than those with
      moderate disease (33 per cent) (p < 0.018). Our data suggest an equal maternal
      and paternal contribution to the inheritance of asthma and an association of the
      homozygous variant (Leu 181/Leu 183) of the IgE receptor FcepsilonRIbeta with
      disease severity.

PMID- 11245346
TI  - Role of folate in preventive medicine.

PMID- 11245347
TI  - Safety and immunogenicity of combined or associated administration of PRP-T
      vaccine with diphtheria, tetanus and pertussis vaccine in Thai children.
AB  - To assess whether the combination of a diphtheria, tetanus and pertussis vaccine
      with a Haemophilus influenzae type b conjugate vaccine (PRP-T) had any effect on
      immunogenicity or safety compared with separate administration of the vaccines,
      158 infants were randomized to receive the vaccines either in association or as a
      combination at 2, 4, and 6 months of age. A total of 126 infants (59 associated,
      67 combination) completed the three-dose regimen and were analysed for
      immunogenicity and safety. With respect to safety, there were no significant
      differences between the two groups. The combination vaccine was well tolerated
      with adverse reactions consisting mainly of transient pain, redness, induration
      and some low-grade fever. With respect to immunogenicity, response to PRP-T
      vaccine was good. Following just two doses, all infants achieved anti-PRP titers
      >0.15 microg/ml, regardless of whether the vaccine was given in combination or
      association. Following three doses, 98.5 per cent of infants in the combination
      group and 98.3 per cent in the association group had titers higher than 1.0
      microg/ml.

PMID- 11245348
TI  - Perinatal outcome in an obstetric cohort of Mozambican women.
AB  - A prospective cohort of 908 consecutively enrolled pregnant women with biparietal
      diameter (DBP) compatible with gestational age equal to or below 21 weeks were
      followed up regularly at 2-4 weeks intervals. Normal antenatal care routine was
      applied. The newborns were followed until 7 days postpartum. The setting was two
      suburban antenatal clinics in Maputo and the delivery ward at the Maputo Central
      Hospital. The main outcome variables were low birth weight (LBW), preterm
      delivery, intrauterine fetal death, perinatal death and small for gestational age
      (SGA). For each of these variables the odds ratio for maternal risk factors was
      estimated with 95 per cent confidence interval and multiple logistic regression
      analysis was used. LBW occurred in 16.2 per cent and low maternal weight, low
      weight gain during pregnancy and not having a living child were risk factors.
      Prevalence of preterm birth was 15.4 per cent and low weight gain during
      pregnancy and malaria in the perinatal period were risk factors. Four per cent of
      mothers delivered stillborns and syphilis serology (positive VDRL test) was a
      risk factor. Perinatal death occurred in 4.7 per cent. These deaths were
      associated with being SGA, LBW or preterm at birth. Of the cohort women, 9.7 per
      cent delivered SGA newborns. It was concluded that maternal constitutional
      factors, particularly maternal weight gain, maternal height and maternal weight
      as well as syphilis and malaria during pregnancy, need to be given attention
      concerning the adverse outcomes addressed. The establishment of an obstetric
      cohort, followed prospectively, was possible in a low-income setting with limited
      numbers lost to follow-up at delivery.

PMID- 11245349
TI  - Vitamin E administration and reversal of neurological deficits in protein-energy
      malnutrition.
AB  - Neurological signs including posterior column, spinocerebellar, retinal, and
      peripheral nerve deficits are being increasingly recognized in vitamin E
      deficiency states. Children suffering from protein-energy malnutrition (PEM)
      revealed significantly reduced serum alpha-tocopherol levels compared to age
      matched normal children, the deficient subjects also exhibited the widely
      recognized signs of tocopherol deficiency. In this prospective therapeutic
      intervention study moderate PEM subjects were administered aqueous oral vitamin E
      supplementation for 6 weeks and compared with control PEM subjects. The
      parameters studied included pre- and post-therapy serum alpha-tocopherol levels,
      alpha-tocopherol lipid ratio, lipid profile, creatine phosphokinase levels, and
      electroneurophysiological studies. Vitamin E supplementation normalized serum
      alpha-tocopherol levels (p < 0.001), alpha-tocopherol lipid ratio (p < 0.001),
      reduced creatine phosphokinase levels (p < 0.01), and reduced neurological signs
      in PEM subjects (p < 0.001). The observed improvement in neurological dysfunction
      among PEM subjects is of great interest, especially in developing countries.
      While larger studies are recommended, the importance of vitamin E administration
      in PEM is being reported.

PMID- 11245350
TI  - A prospective study of nosocomial enteric pathogen acquisition in hospitalized
      children in South India.
AB  - Screening for enteric pathogens in stool samples from 249 children under the age
      of 36 months, admitted to hospital for non-gastrointestinal disorders, was
      positive at admission in 41 (16.4 per cent) in a prospective study of enteric
      pathogen acquisition and diarrhoea in hospitalized children. Infection with
      multiple organisms was found in 31/41 (75.6 per cent) children who were positive
      when screened at admission. Of 194 children who had no enteric pathogens on
      admission and could be followed up for 3 days after discharge, clinical or
      laboratory data showed nosocomial enteric infections in 39 (20.1 per cent).
      Presumed nosocomial infection with more than one organism was seen in only two
      patients and no pathogens were isolated in 14 (35.8 per cent). Children
      presenting to hospital may asymptomatically carry enteric pathogens and
      potentially act as a source of nosocomial infections. One in five children
      admitted into hospital without an enteric infection is at risk of developing a
      nosocomial gastrointestinal infection, with rotavirus being the most common
      aetiological agent.

PMID- 11245351
TI  - Tuberculous granulomas in childhood tuberculous meningitis: radiological features
      and course.
AB  - The clinical course and serial cranial computerized tomographic (CT) findings of
      202 children with tuberculous meningitis (TBM) admitted to Tygerberg Hospital
      between 1985 and 1994 were reviewed with regard to the incidence, CT appearance
      and clinical course of associated intracranial tuberculous granulomas. Thirty
      four patients (16.85 per cent) had associated intracranial granulomas. Thirty
      eight individual lesions were analysed and classified as meningeal, parenchymal
      or ependymal according to their central nervous system (CNS) location. Twenty
      five patients had round to irregular, brain iso-, hypo- or hyperdense meningeal
      granulomas with variable degrees of enhancement and peri-lesional hypodensities.
      Four patients had diffusely enhancing, brain isodense, enplaque-like ependymal
      granulomas associated with the ventricular ependymal lining. Four patients with
      miliary tuberculosis and TBM showed multiple small diffusely enhancing, brain iso
      or hyperdense parenchymal lesions and associated hypodensities on initial CT.
      Although granulomas in the meningeal and ependymal group had the propensity to
      paradoxically enlarge or appear on standard four-drug antituberculosis therapy,
      the majority resolved uneventfully. Rapid resolution of small parenchymal
      granulomas associated with miliary tuberculosis occurred in all cases. Most
      granulomas in this series were co-incidental, asymptomatic CT findings. In rare
      cases, the development or enlargement of a strategically located granuloma may
      result in complications.

PMID- 11245352
TI  - Multiple dose IVIG treatment in neonatal immune hemolytic jaundice.
AB  - Isoimmune hemolytic jaundice due to ABO and Rh blood group incompatibility is an
      important problem in the neonatal period. Intravenous immune globulin (IVIG)
      treatment in isoimmune jaundice has been shown to be effective, but the response
      to treatment is variable. In this study, the effect of multiple doses IVIG
      therapy versus single dose MG therapy was investigated in 61 babies who had ABO
      and Rh hemolytic disease. Patients were divided into three groups. Group I
      received multiple dose IVIG treatment, group II received single dose MG
      treatment, and group III was not given any IVIG. All three groups received
      phototherapy. No exchange transfusion was needed in group I. The rate of exchange
      transfusion was 12 per cent in group II and 33 per cent in group III. Duration of
      phototherapy was shorter in group I than in groups II and III. It was concluded
      that IVIG treatment reduces the need of exchange transfusion in neonatal
      isoimmune hemolytic jaundice by lowering hemolysis. Multiple doses IVIG treatment
      appears to be better at blocking ongoing hemolysis.

PMID- 11245353
TI  - Epidemiologic and clinical characteristics of Kawasaki disease in Shaanxi
      Province, China, 1993-1997.
AB  - The objective of this paper is to describe the epidemiological and clinical
      characteristics of Kawasaki disease (KD) in Shaanxi Province, China during the 5
      year period from January 1993 to December 1997. A province-wide epidemiological
      survey on KD was made by the China-Japan Kawasaki Disease Study Group. The
      questionnaire form and the diagnostic criteria of KD, which were prepared by the
      Japan Kawasaki Disease Research Committee and translated into Chinese, were sent
      to the departments of pediatrics of all the hospitals with 100 beds or more in
      Shaanxi province. All the KD patients who were diagnosed during the observation
      period from 1993 to 1997 were asked to take part in this survey. The databases of
      reported KD in this survey were analysed at the Department of Pediatrics of the
      Shaanxi Provincial People's Hospital, Xi'an, China. All the patients that
      satisfied the diagnostic criteria were included in the report. A total of 105 (70
      per cent) hospitals responded and 376 cases of KD were confirmed. More cases were
      reported in 1993 and 1994. Of the total patients reported, 69 per cent were
      children under 3 years old with a male to female ratio of 1.6:1. The proportion
      of patients with cardiac sequelae was 19 per cent with a male to female ratio of
      3:1. There were four fatal cases with a fatality rate of 1 per cent. It is
      concluded that KD is common in China. Continuous surveillance is necessary to
      maintain high awareness of KD so as to find possible risk factors and their
      association with the disease.

PMID- 11245355
TI  - Co-trimoxazole resistant Brucella.

PMID- 11245354
TI  - Lung function tests in asthma: which indices are better for assessment of
      severity?
AB  - Pulmonary function tests are objective evidence of the severity of asthma. A
      cross-sectional study was carried out to determine the sensitivity of various
      pulmonary function indices in picking up clinically diagnosed mild and severe
      asthma. Three groups, each with 60 subjects between 5 and 15 years all of either
      sex, with mild asthma, severe asthma, and without asthma, respectively, were
      studied. Pulmonary function tests were performed using a portable spirometer.
      FEV1 and FVC could differentiate mild asthma from non-asthmatic children in 38
      (63 per cent) and 35 (58 per cent), respectively. FEF25% and FEF75% could
      identify 46 (77 per cent), and 47 (78 per cent) of mild asthmatic children. In
      children with severe asthma, FEV1, FVC, FEF25%, and FEF75% were abnormal in 54
      (90 per cent), 48 (80 per cent), 58 (97 per cent) and 56 (94 per cent),
      respectively. Peak expiratory flow rate was abnormal in 77 per cent of mild and
      87 per cent of severe asthmatics. The FEV1/FVC ratio showed no significant
      difference between asthmatics and non-asthmatics. It is concluded that FEF25% and
      FEF75% are better indices for assessment of severity of asthma than FEV1 and FVC.
      The ratio FEV1/FVC is not useful.

PMID- 11245356
TI  - Comparison study of the immunogenicity of different types and dosages of
      recombinant hepatitis B vaccine in healthy neonates.

PMID- 11245357
TI  - Accuracy and qualities of real and suggested memories: nonspecific age
      differences.
AB  - This study examined adult age differences in the accuracy, confidence ratings,
      and vividness ratings of veridical and suggested memories. After seeing either
      one or two exposures of a vignette depicting a theft, young adults (M = 19 years)
      and older adults (M = 73 years) were given misleading information that suggested
      the presence of particular objects in the episode. Memory accuracy was higher for
      younger adults than for older adults, and the frequency of falsely reporting the
      presence of suggested objects was greater for older adults than for young adults.
      Further, levels of confidence and vividness ratings of the perceptual attributes
      (colors, locations) of falsely recognized items were higher for older adults than
      for young adults. Both young adults and older adults used more perceptual
      references when describing veridical memories than when describing suggested
      memories. Age differences in the suggestibility of memory were attributed to
      nonspecific or nondissociated memory aging effects.

PMID- 11245358
TI  - Symptoms of depression in the oldest old: a longitudinal study.
AB  - This study examined depressive symptoms in a population-based, longitudinal
      sample of people aged 80 and older to determine initial prevalence of depressive
      symptoms and changes over time. Depressive symptomatology was assessed with the
      Center for Epidemiologic Studies-Depression scale (CES-D). The sample was drawn
      from the OCTO-Twin study, which examined 702 Swedish twins over age 80 in which
      both members of the pair were still surviving. For the present study, one member
      of each twin pair was randomly selected, resulting in a sample of 351. A
      comprehensive biobehavioral assessment was conducted at three time points over 4
      years. Depressive symptoms were initially relatively low and decreased
      significantly between Wave 1 and Wave 2. At Wave 3, depressive symptoms increased
      slightly but not significantly. Participants who received a dementia diagnosis at
      some point in the study did not differ significantly on initial CES-D scores when
      compared to those participants who never received such a diagnosis. Lack of well
      being, as opposed to negative affect, was the biggest contributor to the overall
      depression score at each of the three waves of measurement. Predictors of
      negative affect for this sample included activities of daily living, subjective
      health, and performance on the cognitive test, block design. None of these
      predictors were significant for lack of well-being.

PMID- 11245359
TI  - Encoding tasks and the processing of perceptual information in young and older
      adults.
AB  - This study examined the degree to which different tasks promote the encoding of
      the characteristics of a talker's voice in young and older adults, and whether
      these characteristics encoded in long-term memory facilitate spoken word
      identification under difficult listening conditions. During the encoding phase,
      participants were given extensive exposure to the voices of two talkers and
      performed tasks that focused their attention on either voice characteristics
      (explicitly or incidentally) or linguistic information. Subsequently,
      participants identified novel words masked by noise, half of which were spoken by
      one of the familiar talkers and half by an unfamiliar talker. Young adults
      identified with greater accuracy words spoken in a familiar voice, whereas older
      adults benefited from voice familiarity only under instructions that promoted
      attention to voice characteristics either explicitly or incidentally. Age-related
      declines in sensory uptake (hearing loss) accounted for most of these task
      dependent voice effects.

PMID- 11245360
TI  - Well-being as a moving target: measurement equivalence of the Bradburn Affect
      Balance Scale.
AB  - Although the Bradburn Affect Balance scale (ABS) is a frequently used two-factor
      indicator of well-being in later life, its measurement and invariance properties
      are not well documented. We examined these issues using confirmatory factor
      analyses of cross-sectional (adults ages 54-87 years) and longitudinal data from
      the Victoria Longitudinal Study. Stability of the positive and negative affect
      factors was moderate across a 3-year period. Overall, factor loadings for
      positive affect items were invariant over time with the exception of the pleased
      item. Negative affect items were time invariant. However, age-group comparisons
      between young-old and old-old groups revealed age differences in loadings for the
      upset item at Time 1. Finally, gender groups differed in loadings for the top of
      the world and going your way items. Thus a pattern of partial measurement
      equivalence characterized item response to the ABS. Our results suggest that
      group comparisons and longitudinal change in ABS scale scores of positive and
      negative affect should be interpreted with caution.

PMID- 11245361
TI  - Caregivers' judgments of the functional abilities of the Alzheimer's disease
      patient: a comparison of proxy reports and objective measures.
AB  - The assessment of functional capacity is essential for the diagnosis of dementia
      by DSM-IV criteria and has important implications for patient intervention and
      management. Although ratings of functional disability by family or other proxy
      informants are widely used by clinicians, there have been concerns and empirical
      evidence that potential reporter biases may result in either overestimation or
      underestimation of specific functional deficits. In this study, we compared
      family members' judgments of the functional abilities of seventy-two patients
      diagnosed with Alzheimer's disease (AD). These judgments were compared to actual
      objective functional performance on an array of real-world tasks using the Direct
      Assessment of Functional Status (DAFS) scale. The results indicate that
      caregivers were extremely accurate in predicting the functional performance of AD
      patients who were not impaired during objective evaluation. In contrast,
      caregivers significantly overestimated the ability of impaired AD patients to
      tell time, to identify currency, to make change for a purchase, and to utilize
      eating utensils. Higher patient MMSE scores were associated with caregivers'
      overestimation of functional capacity, while the degree of caregivers' depressive
      symptoms, as measured by the CES-D depression scale, was not related to either
      overestimation or underestimation of patients' functional performance.

PMID- 11245362
TI  - Task specificity in age-related slowing: word production versus conceptual
      comparison.
AB  - We analyzed age-related slowing in 29 younger (M = 22 years) and 30 older adults
      (M = 70 years) who performed a conceptual comparison task, a naming task, and a
      simple reaction time task. Both vocal and manual responses were elicited in all
      except the naming task. Results did not support the hypothesis that there is
      greater age-related slowing in comparison tasks than in production tasks. In
      contrast, we found an interaction between age and response modality in the
      conceptual comparison task. Response latencies of younger participants were
      shorter in the manual modality whereas those of older participants were shorter
      in the vocal modality. In the simple reaction time task manual responses were
      faster in the two age groups. These findings are discussed in relation to models
      assuming task-specific slowing factors.

PMID- 11245363
TI  - Old age is associated with a pattern of relatively intact and relatively impaired
      task-set switching abilities.
AB  - In three experiments, we examined the effects of old age on the reaction time
      (RT) decrement associated with task alternation. Old age was associated with
      increased mixing-cost, which is the RT difference between two conditions: mixed
      task, where trials involving two tasks were intermixed, and single-task, where
      all the trials involved the same task. Old age was also associated with an
      increased switching-cost, which is the RT difference between trials in which the
      task was just changed and trials in which it was repeated. There was also
      indication of a slowed passive dissipation of task set adopted in the preceding
      trial. In contrast to these impairments, old age was also associated with an
      almost intact ability to prepare for an upcoming task switch. This ability was
      indicated by a normal reduction in switching-cost due to an increase in the time
      allowed to prepare for the switch. We discuss the implications of the results in
      relation to theories of task-switching and to the underlying brain mechanisms,
      especially with respect to the effect of old age on the prefrontal cortex.

PMID- 11245364
TI  - Aggregate changes in severe cognitive impairment among older Americans: 1993 and
      1998.
AB  - OBJECTIVES: This study explored whether improvements in cognitive functioning
      occurred during the 1990s among older Americans and investigated several possible
      explanations for such changes. METHODS: Using the 1993 Asset and Health Dynamics
      of the Oldest Old study (N = 7,443) and 1998 Health and Retirement Survey (N =
      7,624), this study examined aggregate changes in the proportion of the
      noninstitutionalized population aged 70 and older with severe cognitive
      impairment. Impairment was measured for self-respondents using a modified version
      of the Telephone Interview Cognitive Screen; for proxy respondents, ratings of
      memory and judgment were used. Logistic regression was used to investigate
      potential explanations for aggregate changes. RESULTS: The percentage of older
      Americans with severe cognitive impairment declined from 6.1% in 1993 to 3.6% in
      1998 (p < .001). The decline was statistically significant among self-respondents
      but not among those with proxy interviews. Improvements between 1993 and 1998
      were not explained by shifts in demographic and socioeconomic factors or by
      changes in the prevalence of stroke, vision, or hearing impairments. DISCUSSION:
      As a group, older persons, especially those well into their 80s, appear to have
      better cognitive functioning today than they did in the early 1990s.

PMID- 11245365
TI  - Social networks among blacks and whites: the interaction between race and age.
AB  - OBJECTIVES: This study examined the main and interactive effects of age and race
      on the core characteristics of social networks including size, frequency of
      contact, geographical proximity, and composition of network. METHODS: Respondents
      were drawn from a stratified probability sample of people aged 20-93 in the
      greater Detroit metropolitan area. Approximately 30% of the sample were African
      American, and people aged 60 and older were over-sampled (n = 1.382). The authors
      used hierarchical regression analysis to estimate the influence of race and age
      on each component of social network, controlling for marital status, gender, and
      education. An interaction term (Race x Age) was added to explore the extent to
      which age moderates any detected race differences. RESULTS: Older age was
      associated with smaller, less frequently seen, and less proximal networks that
      had a higher proportion of kin. Blacks and Whites were similar with regard to
      proximity, but Blacks had smaller networks, more contact with network members,
      and more family members in their networks. Race differences in frequency of
      contact and proportion of kin were moderated by age, such that the differences in
      these variables diminished with increasing age. DISCUSSION: A systematic analysis
      of how age, race, and their interaction influence the characteristics of social
      networks furnishes important empirical knowledge about social networks among
      diverse groups. Such data may provide a context for how, and some explanation for
      why, support exchanges occur.

PMID- 11245366
TI  - Exploring race variations in aging and personal control.
AB  - OBJECTIVES: The purpose of this study is twofold: (a) to see whether the
      association between age and perceived control is the same for Blacks as well as
      Whites; and (b) to see if education, health, income, social support, cognitive
      function, and religion account for the relationship between age and control in
      the same way for Blacks and Whites. METHODS: Data for this study come from the
      first wave of the Americans' Changing Lives panel study. Complete data are
      available for 357 Black and 2,792 White individuals. Respondents were asked
      questions about their feelings of control, health status, income, social support,
      cognitive function, religious participation, and demographic information.
      RESULTS: The findings suggest that age has an inverse and nonlinear association
      with feelings of control. Moreover, this relationship is similar for Blacks and
      Whites. The data further reveal that, across all age groups, Blacks report a
      lower sense of control than Whites. Less education, less income, greater
      cognitive impairments, and more religiosity are associated with a lower sense of
      control. These factors, along with health and social support, account for 69% of
      the association between age and control, with no differences according to race.
      DISCUSSION: These results show that lower levels of control are associated with
      older age in both Blacks and Whites, and that racial disparities in feelings of
      control persist across all age groups. This suggests that Blacks may be at a
      particular disadvantage in the face of the increasing challenges of aging.

PMID- 11245367
TI  - Access to care and functional status change among aged Medicare beneficiaries.
AB  - OBJECTIVES: This study examined whether the extra-individual factors of better
      access to care and supplementary health insurance coverage can prevent, delay, or
      reverse transitions from functional independence to disability over time.
      METHODS: Six years of the Medicare Current Beneficiary Survey were pooled,
      yielding 40,793 transition periods for community residents aged 66 or older.
      Multinomial logit models of transitions among functional states were estimated,
      with functional improvement, functional decline, and mortality as outcomes.
      RESULTS: Insurance coverage and better access to care increased survival chances
      and reduced the odds of transitions from independence to disability by roughly
      30%. Access and supplementary insurance did not appear to affect transitions from
      less disabled to more disabled states or affect functional improvement.
      DISCUSSION: The findings support the hypothesized role of extra-individual
      environmental factors in Verbrugge and Jette's conceptual scheme of the
      disablement process. Access to care is suggested to make the most difference in
      delaying or slowing down functional decline among functionally independent
      elderly persons. Transitions from less severe to more severe states of disability
      or to death appear to be influenced more by the natural course of chronic
      diseases, underlying health status, and medical instability.

PMID- 11245368
TI  - Does an increase in the Medicaid reimbursement rate improve nursing home quality?
AB  - OBJECTIVES: Numerous studies have documented poor nursing home quality over the
      last 3 decades. Previous research has questioned the effectiveness of Medicaid
      reimbursement policy in improving quality in the presence of certificate-of-need
      (CON) and construction moratoria regulation. This study evaluated how the
      Medicaid reimbursement rate may influence a home's decision to provide quality
      under CON and moratoria. METHODS: Linking national data from the On-Line Survey,
      Certification, and Reporting system, the Area Resource File, and aggregate
      reimbursement information, the author examined the effect of Medicaid
      reimbursement on a range of quality measures in the context of CON and moratoria.
      RESULTS: An increase in Medicaid reimbursement improved quality as measured by
      professional staffing, but there was not a statistically significant effect when
      quality was measured by nonprofessional staffing, various procedural measures, or
      regulatory deficiencies. However, this study did not support previous research
      showing a negative effect of Medicaid reimbursement on nursing home quality in
      the context of CON laws. DISCUSSION: This study supports recent trends suggesting
      that nursing home CON laws may be lessening in importance for the nursing home
      market. Nevertheless, further work is necessary to determine the quality returns
      to increased Medicaid reimbursement.

PMID- 11245369
TI  - Factors associated with food insecurity among U.S. elderly persons: importance of
      functional impairments.
AB  - OBJECTIVES: The authors examined factors associated with the food insecurity of
      elderly persons in the United States and particularly how functional impairments
      were associated with food insecurity. METHODS: Data were from the Third National
      Health and Nutrition Examination Survey (1988-94) and the Nutrition Survey of the
      Elderly in New York State (1994). The authors used multiple logistic regression
      and a hierarchical logistic regression analyses to examine how functional
      impairments as well as sociodemographic and economic factors contributed to food
      insecurity in elderly persons. RESULTS: Low income, low education, minority
      status, food assistance program participation, and social isolation were
      significantly related with food insecurity. Functional impairments were
      significantly related with food insecurity among elderly persons even after those
      factors were controlled. DISCUSSION: Food security in elderly persons is
      associated with functional impairments, suggesting that food insecurity in
      elderly persons comprises not only limited food affordability, availability, and
      accessibility but also altered food use. Food-insecure elderly persons experience
      multiple problems that prevent them from achieving nutritional well-being and
      seeking food assistance programs. Nutrition services should recognize and provide
      services to cover those needs.

PMID- 11245370
TI  - Surgical treatment of early-stage breast cancer in the Department of Defense
      Healthcare System.
AB  - BACKGROUND: The choice between breast-conserving surgery and modified radical
      mastectomy in the treatment of women with early stage breast cancer in the
      Department of Defense Healthcare System may be influenced by demographic factors.
      STUDY DESIGN: The Department of Defense Automated Central Tumor Registry (ACTUR)
      was queried for women diagnosed with American Joint Committee on Cancer Stage I
      or II invasive breast carcinoma from January 1, 1986, to December 31, 1996.
      Univariate analysis and multivariate analysis were applied to the study
      variables. Year of diagnosis, age at diagnosis, tumor size, type of hospital,
      geographic region, and local availability of radiation therapy were evaluated
      with respect to the type of surgical treatment performed. Surgical treatment was
      either breast conservation therapy (BCT) or modified radical mastectomy. RESULTS:
      After excluding women for whom the data were incomplete (n = 308), 7,815 women
      were identified who met study criteria. There was a progressive increase in the
      use of BCT to treat tumors of all sizes from 16% to 47% over the 11 years of the
      study (p < 0.0001). BCT was more frequently used for smaller tumors (< 2cm), with
      an odds ratio of 2.46 (2.20-2.76, 95% CI). In 1996, 54% of women with T1 (< 2 cm)
      tumors were treated with BCT. Women treated with BCT were nearly the same age as
      those undergoing modified radical mastectomy (55.5 years versus 56.8 years, p <
      0.0001). BCT was used at a slightly greater rate in medical centers than in
      community hospitals (31% versus 28%, p < 0.0001). Use of BCT varied among
      geographic regions from a low of 24% in the southwestern USA to a peak of 36% in
      the Northeast and 40% in hospitals outside of the continental United States (p <
      0.0001). Local availability of radiation therapy did not influence choice of
      treatment. CONCLUSIONS: The use of BCT to treat early stage invasive breast
      carcinoma in the Department of Defense Healthcare System is increasing. But BCT
      is used less often to treat larger tumors. Regional differences in the use of BCT
      persist, even after controlling for other factors. Patient age and type of
      hospital (community versus academic center) appear to exert little influence on
      the choice of treatment. Local availability of radiation therapy did not seem to
      influence the choice of treatment. Our data suggest that efforts to promote the
      use of BCT should target the central and southwestern USA. Use of BCT should also
      be emphasized for women with larger tumors (> 2 cm).

PMID- 11245371
TI  - Respiratory physiopathology in surgical repair for large incisional hernias of
      the abdominal wall.
AB  - BACKGROUND: The computerized noninvasive measurement of respiratory mechanics
      enables new prospects in the study of respiratory physiopathology in surgical
      repair of large incisional hernias. STUDY DESIGN: We studied 10 patients with
      COPD ventilated with a Servo Ventilator 900C. We measured inspiratory flow by
      means ofa pneumotacograph, the volume by integrating the flow signal, and
      esophageal and airway opening pressure by means of two differential pressure
      transducers (an esophageal balloon measures, separately, chest wall and lung
      mechanical properties). The signals were sent by an analogic-digital converter to
      a personal portable computer to be analyzed. We calculated compliance of total
      respiratory system (Crs), chest wall (Ccw), and lung (CI); maximum resistance of
      the total respiratory system (Rmax, Rs), chest wall (Rmax, w), and lung (Rmax,
      L); and work of breathing (Wob). Statistics were performed using one-way analysis
      of variance and p = 0.05 was considered significant. RESULTS: At the closure of
      the peritoneum a reduction of Crs and Wob was recorded in seven patients in whom
      a PTFE prosthesis widening the abdominal cavity was used to restore the baseline
      value. Variations in respiratory compliance are from variations in Ccw with
      unaffected CI (Ccw varied from 0.180 to 0.130 L/cmH2O at peritoneal closure and
      from 0.130 to 0.170 L/cmH2O by prosthetic peritoneal widening). Respiratory
      resistances remained unchanged (11.3 cmH2O/ L/s) at any time of measurement.
      CONCLUSIONS: The intraoperative assessment of respiratory mechanics is useful to
      evaluate and eventually to decrease the mechanical workload (prosthesis widening
      peritoneum or fascia incisions). The passive mechanical work performed by the
      ventilator needs to be kept constant or no higher than 10% basic data: if these
      conditions are maintained, mostly in patients with COPD, there is no risk of
      respiratory muscular fatigue during the postoperative period.

PMID- 11245372
TI  - Synovial sarcoma in children: surgical lessons from a single institution and
      review of the literature.
AB  - BACKGROUND: Synovial sarcomas are malignant high-grade, soft-tissue neoplasms
      that account for 7% to 8% of all malignant soft-tissue tumors and are the most
      common nonrhabdomyosarcoma soft-tissue sarcomas in pediatric patients. STUDY
      DESIGN: A retrospective review of the records of children younger than 17 years
      with synovial sarcoma treated at the University of Texas MD Anderson Cancer
      Center from 1966 until 1999 was undertaken. Primary site, tumor size, tumor
      margins, surgical treatment, adjuvant therapy, local and distant recurrence, and
      survival were recorded for 42 patients. Overall survival (OS) and progression
      free survival (PFS) rates were calculated by the Kaplan-Meier method. The PFS and
      OS comparisons were performed using the log-rank test. RESULTS: Forty-four
      patients were identified, but two patients were excluded because of incomplete
      records. The median followup duration for the 42 patients was 8.8 years (range
      0.2 to 22.4 years). The 5-year progression-free survival and overall survival
      rates were 75.6% and 87.7%, respectively. Eleven patients were dead and four
      others had progressed but were alive without evidence of disease after further
      therapy. Intergroup Rhabdomyosarcoma Study (IRS) grouping and tumor invasiveness
      were found to be significant prognostic indicators (p < 0.01 and p = 0.02,
      respectively). Patients with initial gross total resection (IRS Groups I and II)
      and noninvasive tumors (T1) were most likely to have prolonged PFS and OS.
      Patients with small tumors (<5 cm) (p = 0.09) had better PFS and OS. Adjuvant
      radiation therapy appeared to be of benefit, and chemotherapy did not seem to
      impact PFS or OS. Tumors > or = 5 cm are associated with increased risk of local
      recurrence and distant metastases. CONCLUSIONS: Complete resection with clear,
      yet not necessarily large, margins remains the treatment of choice for synovial
      sarcoma in children. Adjuvant radiation therapy should possibly be considered in
      patients with clear margins (IRS Group I) and in patients with microscopic
      residual tumor (IRS Group II). Chemotherapy did not seem to impact PFS or OS.
      Lymph nodes should be evaluated for local regional disease.

PMID- 11245373
TI  - The high morbidity of blunt cerebrovascular injury in an unscreened population:
      more evidence of the need for mandatory screening protocols.
AB  - BACKGROUND: Blunt cerebrovascular injuries are rare injuries causing substantial
      morbidity and mortality. The appropriate screening methods and treatment options
      for these injuries are controversial. We examined our experience with these
      injuries at a community Level I Trauma center over a 51 month period. STUDY
      DESIGN: A retrospective review and analysis was done of all patients with the
      diagnosis of a blunt cerebrovascular injury during this period. RESULTS: Fourteen
      patients had blunt carotid injury (0.40%) and three had blunt vertebral injury
      (0.09%) out of 3,480 total blunt admissions. The overall incidence of blunt
      cerebrovascular injury was 0.49%. The most common associated injuries were to the
      head (59%) and chest (47%) regions. The overall mortality rate was 59% (10 of
      17), with death occurring in 8 of 14 (57%) blunt carotid injury patients and 2 of
      3 (67%) blunt vertebral injury patients. Eight of ten (80%) deaths were directly
      attributable to the blunt cerebrovascular injury. Median time until diagnosis was
      12.5 h (range 1-336 h) for the entire group and 19.5 h for nonsurvivors.
      Diagnosis was delayed > 24h in 7 patients and > 48h in 5 patients. All five
      patients whose diagnoses were delayed > 48 h developed complications, and four
      (80%) of these patients died. CONCLUSIONS: Blunt cerebrovascular injury is
      uncommon, but lethal; particularly when the diagnosis is delayed. Aggressive
      screening protocols based on mechanism of injury, associated injuries, and
      physical findings are justified to minimize morbidity and mortality. Head and
      chest injuries may serve as markers for blunt cerebrovascular injury. Most deaths
      are directly attributable to the blunt cerebrovascular injury and not to
      associated injuries.

PMID- 11245374
TI  - Interleukin-6 production in lung tissue after transthoracic esophagectomy.
AB  - BACKGROUND: The mechanisms of the reported high increase in interleukin-6 (IL-6)
      levels after esophagectomy are unclear. We investigated the influence of an
      intrathoracic procedure, esophagectomy, on IL-6 production in lung tissue. STUDY
      DESIGN: Fourteen paired lung tissue samples were obtained from patients before
      and after they underwent transthoracic esophagectomy for esophageal cancer. IL-6
      levels in the lung were measured with enzyme-linked immunosorbent assay, and IL-6
      mRNA expression was determined with real-time quantitative reverse transcription
      polymerase chain reaction. Immunohistochemical staining was used to localize IL
      6, and circulating levels were also measured. RESULTS: IL-6 protein and mRNA were
      significantly increased in lung tissue after this intrathoracic procedure (p <
      0.05). Peak levels of plasma IL-6 after surgery were correlated with IL-6 levels
      in lung tissues obtained after the procedure (p < 0.05). Immunohistochemical
      staining revealed IL-6 production from alveolar and bronchial epithelial cells
      but not from alveolar macrophages. CONCLUSIONS: Transthoracic esophagectomy
      causes an increase in IL-6 production from airway epithelial cells, secondary to
      increased expression of IL-6 mRNA. Local response of lung tissue may be one
      source of increased serum IL-6 after this procedure.

PMID- 11245375
TI  - Safety and longterm efficacy of strictureplasty in 314 patients with obstructing
      small bowel Crohn's disease.
AB  - BACKGROUND: Since its introduction in the early 1980s, strictureplasty (SXP) has
      become a viable option in the surgical management of obstructing small bowel
      Crohn's disease. Questions still remain regarding its safety and longterm
      durability in comparison to resection. Precise indications and contraindications
      to the procedure are also not well defined. STUDY DESIGN: A retrospective review
      of all patients undergoing SXP for obstructing small bowel Crohn's disease at the
      Cleveland Clinic between 1984 and 1999 was conducted. A total of 314 patients
      underwent a laparotomy that included the index SXP The total number of SXPs
      performed was 1,124, with a median of two (range 1 to 19) per patient. Sixty-six
      percent of patients underwent a synchronous bowel resection. Recurrence was
      defined as the need for reoperation. Followup information was determined by
      personal interviews, phone interviews, or both. RESULTS: The overall morbidity
      rate was 18%, with septic complications occurring in 5% of patients. Preoperative
      weight loss (p = 0.004) and older age (p = 0.008) were found to be significant
      predictors of morbidity. The surgical recurrence rate was 34%, with a median
      followup period of 7.5 years (range 1 to 16 years). Age was found to be a
      significant predictor of recurrence (p = 0.02), with younger patients having a
      shorter time to reoperation. CONCLUSIONS: This large series of patients with
      longterm followup confirms the safety and efficacy of strictureplasty in patients
      with obstructing small bowel Crohn's disease. The 18% morbidity and 34% operative
      recurrence rates compare favorably with reported results of resective surgery.
      Caution should be used in patients with preoperative weight loss, because they
      experienced higher complication rates. Although young patients seem to follow an
      accelerated course, SXP remains indicated as part of an overall strategy to
      conserve intestinal length.

PMID- 11245376
TI  - Repeat liver resection for hepatocellular carcinoma.
AB  - BACKGROUND: Although hepatectomy has been accepted as a therapeutic option for
      the primary tumor of hepatocellular carcinoma (HCC), what role the second liver
      resection will play in the clinical care of patients with intrahepatic recurrence
      of HCC after the initial resection has not been well evaluated. STUDY DESIGN: In
      a retrospective review of the 6-year period between January 1991 and December
      1996, records were examined of 94 patients who underwent curative liver resection
      for HCC. Of these, 57 patients had isolated recurrent disease to the liver; 12 of
      the 57 patients underwent repeat surgical resection and 45 patients received
      nonsurgical ablative therapy. Clinical data for these patients were reviewed for
      operative morbidity and mortality, survival, disease-free survival, and pattern
      of failure. RESULTS: There were no perioperative deaths during repeat liver
      resections for recurrent HCC. Operative morbidity in the second resection was
      comparable to the initial resection. The disease-free survival rate after the
      second hepatectomy was 31% at 2 years, significantly lower than that after
      initial hepatectomy (62%) (p = 0.009). The overall survival rate after the second
      hepatectomy was 90% at 2 years, in contrast to 70% after nonsurgical ablative
      treatment for recurrent HCC (p = 0.253). CONCLUSIONS: Although the second liver
      resection for recurrent HCC can be performed safely and may improve survival, the
      disease-free survival rate after such resection therapy is low. This likelihood
      of further recurrences encourages studies for the selection of patients who may
      benefit from repeat liver resection.

PMID- 11245377
TI  - What's new in cardiac surgery.

PMID- 11245378
TI  - What's new in plastic surgery.

PMID- 11245379
TI  - What's new in transplantation.

PMID- 11245380
TI  - Virtual reality: surgical application--challenge for the new millennium.

PMID- 11245381
TI  - Assessing competency: a tale of two professions.

PMID- 11245382
TI  - The ACGME competencies: substance or form? Accreditation Council for Graduate
      Medical Education.

PMID- 11245383
TI  - Anatomy and physiology of lymphatic drainage of the breast from the perspective
      of sentinel node biopsy.
AB  - Knowledge of the anatomy and physiology of the lymphatic system is helpful when
      considering a particular sentinel node biopsy technique. The delicate balance
      between internal and external pressures in a lymphatic channel can be influenced
      by the injection volume and by massage in a negative or positive way. The narrow
      openings in the interendothelial junctions determine the speed of clearance of
      particles with a certain size, and this has implications for the timing of
      lymphoscintigraphy and surgery. Tracer uptake and lymph flow are highly variable
      and depend on a number of factors, some of which are beyond our control. The
      lymphatic anatomy is not completely understood despite numerous studies since the
      end of the 18th century. Several topics have been elucidated in more recent
      studies and through experience with sentinel node biopsy. First, although
      axillary drainage is the principal lymphatic path of the breast, any drainage
      pattern from any quadrant of the breast can occur. Second, most lymph from the
      breast flows to the nodal basins with a direct course, not passing through the
      subareolar plexus. Another relevant point is that gentle massage encourages lymph
      flow and facilitates sentinel node detection. What problems do we still face in
      clinical practice? The optimum size and number of labeled colloid particles
      remain to be established. The optimum volume of the tracer also remains to be
      determined. But the main controversy concerns the injection site. Although the
      intradermal injection technique has attractive practical features, there is
      currently insufficient certainty that drainage of tracer injected anywhere in or
      underneath the skin of the breast reflects drainage from the cancer. Connections
      between collecting lymphatic vessels from the tumor site and the collecting
      vessels from the skin and subdermal lymphatics can explain the concordance
      between intraparenchymal and superficial injections in most patients. To
      determine the technique that yields the best sentinel node identification rate
      with the lowest possible false-negative rate would require a large randomized
      trial with all patients undergoing a complete lymph node dissection and
      evaluation of all other axillary lymph nodes with serial sections and
      immunohistochemistry. Current knowledge about sensitivity is based on examination
      of the other axillary nodes with hematoxylin and eosin staining and not with
      immunohistochemistry, with the exception of two studies. (33,76) In addition, a
      complete level I to III dissection may not have been done in all patients, and it
      is not certain that pathologists removed and examined all the nodes from the
      specimens. The proposed study seems impossible now that routine axillary node
      dissection has been abandoned by the larger centers around the world. Choosing
      the most attractive approach requires determining the aim of lymphatic mapping. A
      superficial injection technique may be adequate when the purpose is to spare
      patients without lymph node metastases in the axilla an unnecessary axillary node
      dissection. An intraparenchymal injection technique should be used when the
      additional purpose is to determine the stage as accurately as possible and to
      identify sentinel nodes elsewhere.

PMID- 11245384
TI  - Abdominal aortic aneurysm and a horseshoe kidney.

PMID- 11245385
TI  - Obturator herniation visualized by multislice helical CT.

PMID- 11245386
TI  - The anterior approach: the right way for right massive hepatectomy.

PMID- 11245387
TI  - Posterior approach for the simultaneous, bilateral thoracoscopic sympathectomy.
AB  - If there is an indication for sympathectomy in the case of severe hyperhidrosis
      or rubeosis, in our opinion the posterior approach is preferable because of the
      advantages in surgical technique and anesthesia. Bilateral treatment can be
      accomplished in a single admission, with all the concomitant advantages.

PMID- 11245388
TI  - Human error in hospitals and industrial accidents.

PMID- 11245389
TI  - Preoperative imaging of nonrecurrent laryngeal nerve.

PMID- 11245390
TI  - Treatment of acute colonic pseudo-obstruction.

PMID- 11245391
TI  - Newborn lung treatment poses risk of intestinal perforation.

PMID- 11245392
TI  - Antibody-mediated immunotoxicity in American kestrels (Falco sparverius) exposed
      to polychlorinated biphenyls.
AB  - Antibody-mediated immune function in adult and recently fledged (30 to 33 d old)
      American kestrels (Falco sparverius) was examined in birds exposed directly, or
      only in ovo, to polychlorinated biphenyls (PCBs). In 1998, 9 mature male and 9
      female kestrels were fed PCBs, whereas 9 females and 10 males served as controls.
      A mixture of Aroclors 1248:1254:1260 suspended in safflower oil was injected into
      the kestrels' food items, while in control diets only the same volume of oil was
      added. The dosage of PCBs was approximately 7 mg/kg kestrel/d, beginning in March
      1998 and continuing for 120 d. In 1998, the antibody-mediated immune response was
      stimulated by immunization and booster vaccinations of the kestrels using a
      nonpathogenic antigen, dinitrophenol-keyhole limpet hemocyanin (DNP-KLH). In
      1999, offspring from three treatment groups based upon maternal exposure to PCBs
      were similarly tested for their antibody response. None of these mothers was
      vaccinated with DNP-KLH the previous year. The maternal groups were: (1) exposed
      to PCBs in 1998 for 120 d, (2) exposed in ovo in 1998 (i.e., mothers were
      produced by PCB-exposed parents), or (3) unexposed to PCBs. Serum antibody levels
      were determined using an enzyme-linked immunosorbent assay (ELISA). In 1998, PCB
      exposed adult females had a significantly higher antibody response than did
      controls, whereas adult males exposed to PCBs had significantly suppressed
      antibody production. For the nestlings produced in 1999, maternal treatment
      significantly affected antibody response. Generally, the antibody response in the
      nestlings was much lower than that seen in adult kestrels. Yet both male and
      female offspring from mothers that had been fed PCBs the previous year had
      significantly higher postbooster anti-DNP-KLH titers than control and in ovo
      exposed maternal groups, thus mimicking the response seen in the adult females
      the previous year. These sex-specific responses in PCB-exposed birds provide
      further evidence of the endocrine-disrupting behavior of PCBs. Both suppression
      and stimulation of the antibody response are undesirable because this indicates
      that the immune system is not able to respond normally to challenges by
      infectious or other disease-causing agents.

PMID- 11245393
TI  - Relationships between plasma levels of organochlorines, retinol and thyroid
      hormones from polar bears (Ursus maritimus) at Svalbard.
AB  - Associations were determined between retinol and the thyroid hormones thyroxine
      (T4) and triiodothyronine (T3), respectively, and the organochlorine contaminants
      (OCs) polychlorinated biphenyls (PCBs), 1, 1-dichloro-2,2-bis-(4
      chlorophenyl)ethylene (DDE), hexachlorobenzene (HCB), and hexachlorocyclohexanes
      (HCHs) in blood plasma from polar bears (Ursus maritimus) caught at Svalbard. The
      blood samples were collected from free-ranging polar bears of different age and
      sex in 1991-1994. The retinol concentration and the ratio of total T4 (TT4) to
      free T4(FT4) (TT4/FT4 ratio) decreased linearly with increasing concentrations of
      PCBs and HCB. Retinol was also negatively associated with HCHs, while the TT4/FT4
      ratio was positively associated with DDE. The concentrations of retinol and
      thyroid hormones were significantly higher in females than in males. However, the
      TT4/FT4 and TT3/FT3 ratios were significantly higher in males than in females.
      The concentrations of thyroid hormones were negatively correlated with age in
      male bears, while in females, thyroid hormones did not change with age. The OCs
      were found to explain 12, 30, and 7% of the variation of retinol concentrations
      and the TT4/FT4 and TT3/FT3 ratios, respectively, after correcting for age and
      sex. The potential consequence of these associations for the individual and the
      population is unknown.

PMID- 11245394
TI  - Investigation of organophilic montmorillonite clay inclusion in zearalenone
      contaminated diets using the mouse uterine weight bioassay.
AB  - Previous studies with low-pH montmorillonite (LPHM) clay exchanged with
      alkylammonium compounds showed that these organo clays were quite effective in
      sorbing the estrogenic mycotoxin zearalenone (ZEN) from aqueous solution. The
      potential toxicity of these types of clays, in particular
      hexadecyltrimethylammonium (HDTMA) LPHM, led to the investigation of the sorption
      efficacy of clay exchanged with a less toxic primary amine analog, hexadecylamine
      (HDA). Isothermal analysis studies showed that HDA LPHM was able to bind ZEN, but
      less effectively than HDTMA LPHM as evidenced by a significantly lower Freundlich
      K (63,900 vs. 845). The in vivo effectiveness of these two clays to bind ZEN was
      tested utilizing the mouse uterine weight bioassay. At a dietary inclusion level
      of 0.25%, the clays did not have a negative impact on overall animal health as
      measured by final body weight; however, they did not protect the animals from the
      estrogenic effects induced by 35 mg ZEN/kg in the feed (i.e., the uterine weights
      were not reduced in comparison to ZEN alone). In fact, the HDTMA LPHM group
      showed an increase in uterine weight that was more than the ZEN treatment group.
      When the animals were fed 0.5% clay, both exchanged clays (i.e., HDTMA LPHM and
      HDA LPHM) resulted in decreased body weight gain. The uterine weights of ZEN-fed
      animals (either alone or in combination with clays) were not significantly
      different from each other. In contrast, the uterine:body weight ratio showed a
      dramatic increase in the groups fed exchanged clay + ZEN compared to ZEN alone.
      These results suggest that alkylamine groups may assist the transport or uptake
      of ZEN and result in an enhanced toxicity from contaminated feed. The findings
      from this study clearly demonstrate the need for careful testing of all mycotoxin
      binding agents before their inclusion in the diet.

PMID- 11245395
TI  - In vitro effects of metal ions (Fe2+, Mn2+, Pb2+) on sperm motility and lipid
      peroxidation in human semen.
AB  - The effects of divalent manganese ion (Mn2+), ferrous iron (Fe2+), and lead ion
      (Pb2+) on human sperm motility and lipid peroxidation were examined. Human semen
      from healthy male volunteers was incubated with 0, 5, 50, or 500 ppm divalent
      metal ions, and the sperm motility was determined at 0, 2, 4, 6, or 8 h by
      microscopy. Malondialdehyde (MDA) levels in seminal plasma was measured by high
      performance liquid chromatography after 8 h of exposure. The results showed that
      500 ppm Mn2+ or Pb2+ significantly inhibited sperm motility without an
      accompanying change in seminal MDA levels. Incubation with Fe2+ significantly
      inhibited sperm motility at 5 ppm, associated with a marked rise in MDA levels.
      Our results suggested that Fe2+ may induce lipid peroxidation to inhibit sperm
      motility. In the case of Mn2+ and Pb2+ there is an absence of seminal lipid
      peroxidation and the observed inhibition of sperm motility at high concentrations
      is not biologically or environmentally relevant.

PMID- 11245396
TI  - Cadmium absorption in mice: effects of broiling on bioavailability of cadmium in
      foods of animal origin.
AB  - The absorption and organ distribution of organic Cd from raw and broiled horse
      kidney was compared to that of CdCl2 at two dose levels (0.05 and 3 mg Cd/kg
      feed) in a feeding study in mice. The high Cd concentration in the horse kidney
      (raw 112 mg/kg; broiled 53 mg/kg) made it possible to mix kidney into mouse feed
      without marked effects on the composition of the feed. The weight of the mice,
      feed and water consumption, and Cd levels in the feed were determined once a
      week. After 9 wk of exposure, the liver and kidneys of the mice were sampled and
      Cd was analyzed. The Cd concentration in horse kidney was halved by broiling, and
      the content of soluble Cd decreased from 12% in raw kidney to 5% in broiled
      kidney. The majority of the soluble Cd was associated with proteins with the same
      molecular weight as metallothionein (MT) in both raw and broiled kidney. Broiling
      of the kidney had no marked effect on the fractional accumulation of organic Cd
      in mice. The fractional accumulation of inorganic CdCl2, on the other hand, was
      significantly higher than that of organic Cd in the low dose groups but not in
      the high dose groups. The ratio between Cd accumulation in kidney and that in
      liver was higher in the group receiving raw kidney compared to the ratio in the
      group receiving CdCl2 at both the high and low exposure levels. This indicates
      that the raw kidney contained a Cd form that was more preferentially distributed
      to the kidneys.

PMID- 11245397
TI  - Uracil moiety is required for toxicity of the cyanobacterial hepatotoxin
      cylindrospermopsin.
AB  - A new natural derivative of the sulfated guanidinium zwitterionic toxin
      cylindrospermopsin, 7-epi-cylindrospermopsin, was recently isolated from the
      cyanobacterium Aphanizomenon ovalisporum (Forti). The toxicity of the molecule
      (LD50 ip 5 d), estimated by mouse bioassay, was 200 microg/kg mouse, a value
      similar to that of cylindrospermopsin. Treatment of cylindrospermopsin with
      chlorine solution or chlorine-related oxidants produced two new derivatives. The
      chemical structure of these products was elucidated by nuclear magnetic resonance
      (NMR) and mass spectrometry (MS) techniques and toxicity was determined. In the
      first derivative, the vinylic proton at position 5 of the pyrimidine ring was
      substituted by chlorine to yield 5-chlorocylindrospermopsin. The other product is
      a truncated one, where C-6 of the pyrimidine ring was oxidized to a carboxylic
      acid. A trivial name, cylindrospermic acid, was given to this compound. Both
      products showed no toxic effects even at doses 50 times higher than the LD50 of
      cylindrospermopsin (10 mg/kg mouse ip). Based on these results, the pyrimidine
      ring is postulated as the molecule component essential for the toxicity of
      cylindrospermopsin.

PMID- 11245399
TI  - Marine natural products.

PMID- 11245398
TI  - Effects of subchronic parathion exposure on cyclosporine pharmacokinetics in
      rats.
AB  - Parathion undergoes enzymatic oxidation by hepatic cytochrome P-450 (CYP450)
      enzymes to the active metabolite paraoxon. Consequently, alterations in CYP450
      dependent oxidation may affect the pharmacokinetics and pharmacodynamics of drugs
      that are metabolized in the liver. The CYP3A family is known to be responsible
      for the majority of cyclosporine metabolism. The aim of the present study was to
      assess the disposition kinetics of cyclosporine during subchronic parathion
      exposure. Male Wistar rats were administered either water or two different doses
      of parathion (1/100 LD50, 1/25 LD50; LD50 = 14 mg/kg) by gavage for 6 wk.
      Subsequently, rats in each experimental group received a single oral dose of
      cyclosporine (10 mg/kg), and serial blood samples were drawn from the carotid
      artery over a period of 48 h. Pharmacokinetic analysis showed that parathion
      increased the blood cyclosporine concentration twofold as evidenced by AUC (area
      under the curve), half life (t 1/2) and peak plasma concentration (Cmax). This
      may be due to inhibition of cyclosporine metabolism, an interaction that may be
      of clinical relevance in immunosuppression therapy.

PMID- 11245400
TI  - The biosynthesis of plant alkaloids and nitrogenous microbial metabolites.

PMID- 11245401
TI  - Simple indole alkaloids and those with a nonrearranged monoterpenoid unit.

PMID- 11245402
TI  - Diterpenoids.

PMID- 11245403
TI  - Amaryllidaceae, Sceletium, imidazole, oxazole, thiazole, peptide and
      miscellaneous alkaloids.

PMID- 11245404
TI  - Hot off the press.

PMID- 11245405
TI  - Prevention of disease with pharmaceuticals.
AB  - The idea that diseases such as cardiovascular disease and cancer can be prevented
      by taking a 'pill' is attractive to many people. Chemoprevention is an
      established method in the primary and secondary prevention of cardiovascular
      disease such as myocardial infarct and stroke. Clinical trials have demonstrated
      beyond reasonable doubt that both fatal and non-fatal coronary events and strokes
      can be prevented. Antihypertensive drugs have been shown to be effective through
      clinical trials in preventing myocardial infarctions, stroke and other
      cardiovascular morbidity and mortality. Statins are commonly used to lower the
      blood cholesterol concentration, and aspirin is widely used to prevent occlusive
      vascular disease. Aspirin and other non-steroidal antiinflammatory agents have
      shown promise in the chemoprevention of colorectal cancer. While observational
      epidemiological studies have consistently suggested that diets rich in
      antioxidants such as beta-carotene might be useful in preventing coronary heart
      disease and cancer, the published reports of randomized trials clearly indicate
      that beta-carotene supplements are of no value in persons of high risk for such
      conditions. Although the chemoprevention of cancer is decades behind that of
      cardiovascular disease, there is no reason to believe that progress in cancer
      chemoprevention will differ substantially from that in cardiovascular disease.
      Better understanding of the molecular steps critical to carcinogenesis should
      open new avenues for cancer chemoprevention.

PMID- 11245406
TI  - Diphenyl diselenide and ascorbic acid changes deposition of selenium and ascorbic
      acid in liver and brain of mice.
AB  - Sodium selenite (Na2SeO3) is the selenium form used in the composition of dietary
      supplements, and diphenyl diselenide (PhSe)2 is an important intermediate in
      organic synthesis, which increases the risk of human exposure to this chemical in
      the workplace. These compounds have been reported to inhibit the cerebral and
      hepatic aminolevulinic acid dehydratase (ALA-D) in vitro, and now we show that
      ascorbic acid can reverse some alterations caused by in vivo selenium exposure,
      but not ALA-D inhibition. The effect of Na2SeO3 or (PhSe)2 and ascorbic acid on
      selenium distribution, total non-protein thiol, ascorbic acid content (liver and
      brain) and haemoglobin was also examined. Mice were exposed to 250 micromol/kg
      (PhSe)2, or 18.75 micromol/kg Na2SeO3 subcutaneously, and to ascorbic acid, twice
      a day, 1 mmol/kg intraperitonially, for 10 days. Hepatic ALA-D of mice treated
      with (PhSe)2 was inhibited about 58% and similar results were observed in the
      animals that received ascorbic acid supplementation (P<0.01, for (PhSe)2-treated
      and (PhSe)2+ascorbic acid-treated mice). The haemoglobin content decreased after
      treatment with (PhSe)2 (P<0.01). However, the haemoglobin content of the
      (PhSe)2+ascorbic acid group was significantly higher than in the (PhSe)2-treated
      mice (P<0.05), and similar to control (P>0.10). Ascorbic acid treatment decreased
      significantly the hepatic and cerebral deposition of Se in (PhSe)2-exposed mice
      (P<0.01). Hepatic non-protein thiol content was not changed by treatment with
      (PhSe)2, ascorbic acid or (PhSe)2+ascorbic acid. Hepatic content of ascorbic acid
      was twice that in mice that received (PhSe)2, independent of ascorbic acid
      treatment (P<0.001). The results of this study suggest that vitamin C may have a
      protective role in organodiselenide intoxication.

PMID- 11245407
TI  - The ototoxic effects induced in rats by treatment for 12 weeks with 2
      butenenitrile, 3-butenenitrile and cis-2-pentenenitrile.
AB  - Brainstem auditory and visual evoked-potentials were studied in male Sprague
      Dawley rats during subchronic oral treatment with three unsaturated aliphatic
      nitriles. The rats were given, by gastric intubation, doses of 10, 20 and 40 mg x
      kg(-1) 3-butenenitrile (allyl cyanide) and 25, 50 and 100 mg x kg(-1) of either
      cis/trans-2-butenenitrile (crotononitrile) or cis-2-pentenenitrile once a day, 5
      days per week for 12 weeks. Oral administration of the three unsaturated nitriles
      produced deafness and absence of reaction when the animals were subject to
      droptest. Rats in the high dosage groups exhibited a complete disappearance of
      the five waves of the auditory evoked-potentials. There was a decrease in the
      amplitudes of the 2nd component of the auditory evoked-potentials. Those changes
      were not reversible at the 8th week of the recovery period. A dose-dependent
      effect on inner and outer hair cells was observed in the organ of Corti. The
      basal part of the cochlea was the most affected. Though no measurements were made
      of systemic exposure, a tentative ranking of decreasing ototoxicity of these
      three unsaturated nitriles might be proposed based on the electrophysiological
      deficiencies and histological losses observed: 3-butenenitrile >cis-2
      pentenenitrile >cis/trans-2-butenenitrile. Moreover, rats treated with those
      nitriles showed a corneal opacity as well as a decrease in the amplitude and
      lengthening of the peak latencies of the visual evoked-potentials. These latter
      changes were reversible by the end of the 8th week of the recovery period and
      appeared to be related to the opacity of the cornea.

PMID- 11245408
TI  - Autoprotection in acetaminophen intoxication in rats: the role of liver
      regeneration.
AB  - Autoprotection by acetaminophen, i.e. increased resistance to toxic effects
      caused by pretreatment, is a well-known phenomenon. The purpose of the present
      work was to identify mechanisms for increased acetaminophen tolerance induced by
      pretreatment of rats. One group of female Wistar rats (pretreated rats) received
      acetaminophen orally in increasing doses (1 to 4.3 g/kg) twice a week for 3
      weeks, one group (naive rats) received the vehicle. At time zero pretreated rats
      received a toxic dose of 7.5 g/kg (100% lethal in naive rats), and naive rats
      received a toxic dose of 4.3 g/kg. Blood and liver tissue were collected before
      and 12, 24, 36, and 48 hr after the toxic dose and were analysed for hepatic
      glutathione and cysteine contents, hepatic glutathione-S-transferase and blood
      alanine aminotransferase activity, as well as acetaminophen concentration in
      plasma. Steady-state mRNA levels of proteins involved in acetaminophen
      detoxification, cell division and acute phase response were measured, liver
      tissue was examined for proliferating cell nuclear antigen and degree of
      hepatocyte necrosis. Six naive rats not receiving acetaminophen served as
      controls. The mortality was the same in pre-treated and naive rats (33 percent).
      Thus, pretreatment increased the tolerance twice. Before the toxic dose
      pretreated rats compared to control rats had higher activity of glutathione-S
      transferase (liver) and alanine aminotransferase (serum), higher hepatic mRNA
      level of glutathione-S-transferase and gamma-glutamylcysteine synthetase heavy
      and light chain subunits, and lower hepatic concentration of glutathione,
      cysteine and mRNA of CYP1A2 than control rats. After the toxic dose, the mRNA
      levels of glutathione-S-transferase, gamma-glutamylcysteine synthetase heavy and
      light chain subunits, and CYP1A2 in naive rats rose, approaching those of
      pretreated rats. Proliferating cell nuclear antigen labelling was high in
      pretreated rats, while only slightly increased in a few of the naive rats.
      Necrotic hepatocytes were found at all time intervals in pretreated rats, and in
      naive rats they appeared after 12 hr, peaking after 36 hr. Pretreatment increased
      the tolerance to acetaminophen toxicity twice, as estimated by mortality. The
      data indicate that pretreatment may reduce the relative production of toxic
      metabolites, but it primarily enhances the protection against these metabolites
      by regenerating hepatocytes.

PMID- 11245409
TI  - Immunolocalisation of cytochrome P-450 3A enzymes in human breast carcinoma:
      relationship with tumour differentiation and steroid receptors.
AB  - Cytochrome P-450 3A enzymes belong to the most abundant subfamily of the
      cytochrome P-450 system. They are predominantly found in the liver where they
      metabolize numerous drugs and endogenous substances such as oestrogens. However,
      they are also expressed by normal and tumoural extrahepatic tissues. Accordingly,
      immunolocalization was assessed in malignant breast tumours (n=32) and normal
      counterparts, by using a monoclonal antibody that recognizes all human CYP3A
      proteins. We investigated a potential relation between expression of CYP3A
      protein expression, the degree of tumour differentiation assessed by the
      histological grade and the proliferation index assessed by Ki-67 immunostaining.
      Immunodetection of CYP3A was observed in 27 of the 32 tumours analyzed (84%). A
      focal staining was also observed in the adjacent normal breast tissue in 33% of
      the samples, but expression was always fainter than in tumours. A significant
      negative association was found between CYP3A and the proliferation index, but
      there was no relation with receptor status or tumour differentiation. While CYP3A
      protein expression can be found in normal breast tissues, these data highlight
      higher and more frequent CYP3A in malignant breast cells. Such expression in
      malignant breast cells appears inversely related to the proliferation index
      whereas no relation is found with tumour differentiation.

PMID- 11245411
TI  - Effects of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) on alpha2
      adrenoceptors which regulate the synthesis and release of noradrenaline in the
      rat brain.
AB  - N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) induces a degeneration of
      noradrenergic axons originating in the locus coeruleus. The sensitivity of alpha2
      adrenoceptors which regulate the synthesis and release of noradrenaline was
      investigated in three brain regions which receive an unequal innervation from
      locus coeruleus, 21 days after DSP4 (50 mg/kg) administration. After giving
      treated rats a dopa decarboxylase inhibitor, the in vivo tyrosine hydroxylase
      activity and the tissue concentrations of noradrenaline were also evaluated.
      Relevant reductions of noradrenaline levels were found in hippocampus and
      parietal cortex (91% and 77.5%, respectively; P<0.001) together with a less
      pronounced reduction in hypothalamus (32%, P<0.01). The administration of the
      neurotoxin led to decreases of the basal tyrosine hydroxylase activity,
      determined as the accumulation of 3,4-dihydroxyphenylalanine, in hippocampus and
      parietal cortex (75% and 50.5%, respectively; P<0.001), but not in hypothalamus.
      The inhibitory effect of clonidine on tyrosine hydroxylase activity was markedly
      reduced in hippocampus of rats treated with DSP4 (10+/-5% vs 57+/-3% in the
      control group, P<0.001) but was not changed in parietal cortex and hypothalamus.
      Moreover, in hippocampus, a lack of functionality of the alpha2-adrenoceptors
      which regulate K(+)-evoked [3H]noradrenaline release was determined. However, in
      cortical synaptosomes the concentration-effect curve for the oxymetazoline
      shifted to the right. The administration of the neurotoxin did not modify the
      inhibitory effects of the agonist in hypothalamus. These results support the
      previously described selectivity of DSP4 for noradrenergic terminals arising from
      locus coeruleus and suggest a more severe lesioning of the hippocampus than the
      parietal cortex.

PMID- 11245412
TI  - Inhibition of histone deacetylase activity by trichostatin A modulates gene
      expression during mouse embryogenesis without apparent toxicity.
AB  - Remodeling of the chromatin template by inhibition of histone deacetylase (HDAC)
      activities represents a major goal for transcriptional therapy in neoplastic
      diseases. Recently, a number of specific and potent HDAC-inhibitors that modulate
      in vitro cell growth and differentiation have been developed. In this study we
      analyzed the effect of trichostatin A (TSA), a specific and potent HDAC
      inhibitor, on mouse embryos developing in vivo. When administered i.p. to
      pregnant mice (at a concentration of 0.5-1 mg/kg) at postimplantation stages
      (embryonic day 8 to embryonic day 10), TSA was not toxic for the mother and did
      not cause any obvious malformation during somitogenesis or at later stages of
      development. Treated embryos were born at similar frequency and were
      indistinguishable from control animals, developed normally, and were fertile.
      Interestingly, embryos from TSA-treated mice killed during somitogenesis were
      modestly but consistently larger than control embryos and presented an increased
      (+2 to +6) number of somites. This correlated with an increased acetylation of
      histone H4, the number of somites expressing the myogenic factor Myf-5, and the
      expression of Notch, RARalpha2, and RARbeta2 mRNAs. These data indicate that the
      effects of TSA on transcription: (a) are not toxic for the mother; (b)
      transiently accelerated growth in mouse embryos without perturbing embryogenesis;
      and (c) do not result in teratogenesis, at least in rodents. Thus, TSA might
      represent a nontoxic and effective agent for the transcriptional therapy of
      neoplasia.

PMID- 11245410
TI  - Apomorphine-induced aggressive behaviour in para-chlorophenylalanine-treated male
      rats: implications to brain.
AB  - The aim of this study was to investigate the role of serotoninergic
      neurotransmission and the effect of acute para-chlorophenylalanine (350 mg/kg,
      intraperitoneally) treatment on apomorphine-induced aggressive behaviour in adult
      male Wistar rats. In addition, [3H]ketanserin binding and monoamine content were
      studied. Repeated administration of apomorphine (1.0 mg/kg, subcutaneously, once
      daily for two weeks) gradually induced aggressive behaviour. Acute p
      chlorophenylalanine treatment down-regulated the [3H]ketanserin binding and
      reduced over 90 per cent the content of serotonin and 5-hydroxyindolacetic acid.
      In a half of the p-chlorophenylalanine-treated animals, the aggressive behaviour
      was suppressed, while there was no difference in [3H]ketanserin binding or
      monoamine content between the p-chlorophenylalanine treated aggressive and non
      aggressive animals. In conclusion, the acute p-chlorophenylalanine treatment
      attenuates the aggressiveness only in half of the animals, while the latter
      phenomenon is independent on the CNS monoamine content or [3H]ketanserin binding.

PMID- 11245413
TI  - The ZNF217 gene amplified in breast cancers promotes immortalization of human
      mammary epithelial cells.
AB  - The functional consequences of overexpression of a candidate oncogene on
      chromosome 20q13.2, ZNF217, were examined by transducing the gene into finite
      life span human mammary epithelial cells (HMECs). In four independent
      experiments, ZNF217-transduced cultures gave rise to immortalized cells. HMECs
      that overcame senescence initially exhibited heterogeneous growth and continued
      telomere erosion, followed by increasing telomerase activity, stabilization of
      telomere length, and resistance to transforming growth factor beta growth
      inhibition. The incremental changes in telomerase activity and growth that
      occurred in ZNF217-transduced cultures after they overcame senescence were
      similar to the conversion pattern we have described previously in rare HMEC lines
      immortalized after exposure to a chemical carcinogen. Aberrant expression of
      ZNF217 may be selected for during breast cancer progression because it allows
      breast cells to overcome senescence and attain immortality.

PMID- 11245414
TI  - The effects of angiopoietin-1 and -2 on tumor growth and angiogenesis in human
      colon cancer.
AB  - Angiopoietin (Ang) 1 and Ang-2 are important regulators of endothelial cell
      survival. Current models suggest that an increase in Ang-2 expression in
      endothelial cells leads to initiation of angiogenesis. We stably transfected HT29
      colon cancer cells with cDNA constructs for Ang-1 or -2 or with vector alone,
      injected the cells s.c. into nude mice, and assessed tumor growth.
      Immunohistochemical analyses confirmed sustained increases of Ang-1 and -2 in the
      tumors. The tumors produced by the Ang-2-transfected cells were larger than the
      tumors produced in the other groups; those tumors also had higher vessel counts
      and proliferative indices than tumors in the other groups. Tumors produced by the
      Ang-1 transfectants had fewer vessels and lower tumor cell proliferative indices
      than tumors in the other groups. These data suggest that imbalances between Ang-1
      and -2 that result in a net gain of Ang-2 activity lead to enhanced tumor
      angiogenesis and growth.

PMID- 11245415
TI  - Apoptosis induction by the photosensitizer verteporfin: identification of
      mitochondrial adenine nucleotide translocator as a critical target.
AB  - We report that the photosensitizer verteporfin kills lymphoma cells by an
      apoptotic process involving a dissipation of the mitochondrial inner
      transmembrane potential (deltapsim). Light-activated verteporfin-induced
      apoptosis was abolished by transfection with Bcl-2, a procedure reported to
      inhibit the mitochondrial permeability transition pore complex (PTPC).
      Verteporfin triggered the deltapsim loss in isolated mitochondria in vitro, and
      this effect was suppressed by bongrekic acid and cyclosporin A. Verteporfin plus
      light also permeabilized proteoliposomes containing the semipurified PTPC or the
      purified PTPC component adenine nucleotide translocator (ANT), yet had no effect
      on protein-free control liposomes. Verteporfin phototoxicity on ANT
      proteoliposomes was mediated by reactive oxygen species and was prevented by
      recombinant Bcl-2 or the adenine nucleotides ATP and ADP. In conclusion,
      verteporfin belongs to a class of clinically used chemotherapeutic agents acting
      on PTPC and ANT.

PMID- 11245416
TI  - The fibroblast growth factor receptor 3 (FGFR3) mutation is a strong indicator of
      superficial bladder cancer with low recurrence rate.
AB  - We analyzed the possible prognostic value of the recently discovered fibroblast
      growth factor receptor 3 (FGFR3) mutations in bladder cancer. A FGFR3 mutation
      was found in 34 of 53 pTaG1-2 bladder cancers, whereas none of the 19 higher
      staged tumors had a mutation (P < 0.0001). In 57 patients with superficial
      disease followed prospectively by cystoscopy for 12 months, 14 of 23 patients in
      the wild-type FGFR3 group developed recurrent bladder cancer compared with only 7
      of 34 patients in the mutant group (P = 0.004). The recurrence rate per year was
      0.24 for the FGFR3 mutant tumors and 1.12 for tumors with a wild-type FGFR3 gene.
      In addition, FGFR3 mutation status was the strongest predictor of recurrence when
      compared with stage and grade (P = 0.008). This is the first mutation in bladder
      cancer that selectively identifies patients with favorable disease
      characteristics. Our results suggest that the frequency of cystoscopic
      examinations can be reduced considerably in patients with FGFR3-positive tumors.

PMID- 11245417
TI  - Age-associated risk of cancer among individuals with N-acetyltransferase 2 (NAT2)
      mutations and mutations in DNA mismatch repair genes.
AB  - Mutations in N-acetyltransferase 2 (NAT2), a highly polymorphic enzyme involved
      in the metabolism of xenobiotics and carcinogens, may affect risk for colorectal
      cancer (CRC), especially among individuals with germ-line mutations in DNA
      mismatch repair genes. We determined the NAT2 genotypes and allele frequencies
      for 86 individuals with CRC who had mutations in hMLH1, hMSH2, or hPMS1. No
      significant difference in time to onset was observed between rapid (NAT2*4) and
      slow (NAT2*5, NAT2*6, and NAT2*7) acetylators. However, when individuals were
      stratified separately by NAT2 polymorphism (NAT2*5, NAT2*6, and NAT2*7), those
      who were heterozygous at the mutant locus NAT2*7 after adjustment for the NAT2
      mutant loci NAT2*5 and NAT2*6 had a significantly higher risk of CRC (hazard
      ratio, 2.96; P = 0.012) and all of the cancers (hazard ratio, 3.37; P = 0.00004)
      than individuals homozygous for wild type at the NAT2*7 allele. These findings
      suggest that NAT2 genotype may be an important factor in tumorigenesis of CRC and
      cancers related to hereditary nonpolyposis CRC among individuals with mismatch
      repair defects.

PMID- 11245419
TI  - Coexpression of the partial androgen receptor enhances the efficacy of prostate
      specific antigen promoter-driven suicide gene therapy for prostate cancer cells
      at low testosterone concentrations.
AB  - The prostate specific antigen (PSA) promoter/enhancer has been clearly
      demonstrated to be tissue specific, and has been applied to prostate-specific
      gene therapy. However, the transcription of the PSA gene is strictly androgen
      dependent, and its promoter activity is very weak at low concentrations of
      testosterone, which are generally observed in prostatic cancer patients treated
      with androgen deprivation. In this study, we used a partial androgen receptor
      (ARf) containing amino acids 232-429 and 481-657 to transactivate the PSA gene
      without androgens. We made two expression vectors, ARfPPLUC and ARfPPTK. They
      contained ARf cDNA driven by cytomegalovirus promoter and cDNAs of either firefly
      luciferase (LUC) or herpes simplex virus thymidine kinase (TK) driven by PSA
      promoter/enhancer (PP). The expressed ARf enhanced the PP activity by about 110
      fold in the PSA-producing prostate cancer cell line, LNCaP, under low
      testosterone concentrations. Moreover, in a PSA-nonproducing prostate cancer cell
      line, DU145, ARf also enhanced the PP activity by about 60-fold in an androgen
      independent manner. In a growth inhibition assay, ARfPPTK treated with
      ganciclovir was found to inhibit the cell growth of LNCaP cells much more
      effectively than PPTK. Furthermore, in contrast to PPTK, ARfPPTK also had an
      inhibitory effect on DU145 cells. This system is thus considered to provide a
      useful therapeutic option in patients with prostate cancer who are receiving
      hormonal therapy.

PMID- 11245418
TI  - Hydroxamate-type matrix metalloproteinase inhibitor batimastat promotes liver
      metastasis.
AB  - Overexpression of matrix metalloproteinases (MMPs) facilitates tumor cell
      invasion. Synthetic MMP inhibitors such as batimastat have been designed to treat
      cancer. We report that because of batimastat treatment, human breast carcinoma
      cells metastasized to the liver in nude mice and that an increase of liver
      metastases of murine T-cell lymphoma cells was observed in syngeneic mice.
      Batimastat treatment also caused liver-specific overexpression of MMPs-2, -9, and
      mRNA up-regulation of angiogenesis factors and caspase-1, even in tumor-free
      animals. Induction of organ-specific side effects need to be taken into account
      regarding further development and clinical use of synthetic MMP inhibitors.

PMID- 11245420
TI  - CEP1612, a dipeptidyl proteasome inhibitor, induces p21WAF1 and p27KIP1
      expression and apoptosis and inhibits the growth of the human lung adenocarcinoma
      A-549 in nude mice.
AB  - The ubiquitin proteasome system is responsible for the proteolysis of important
      cell cycle and apoptosis-regulatory proteins. In this paper we report that the
      dipeptidyl proteasome inhibitor, phthalimide-(CH2)8CH-(cyclopentyl) CO-Arg(NO2)
      Leu-H (CEP1612), induces apoptosis and inhibits tumor growth of the human lung
      cancer cell line A-549 in an in vivo model. In cultured A-549 cells, CEP1612
      treatment results in accumulation of two proteasome natural substrates, the
      cyclin-dependent kinase inhibitors p21WAF1 and p27KIP1, indicating its ability to
      inhibit proteasome activity in intact cells. Furthermore, CEP1612 induces
      apoptosis as evident by caspase-3 activation and poly(ADP-ribose) polymerase
      cleavage. Treatment of A-549 tumor-bearing nude mice with CEP1612 (10 mg/kg/day,
      i.p. for 31 days) resulted in massive induction of apoptosis and significant
      (68%; P < 0.05) tumor growth inhibition, as shown by terminal
      deoxynucleotidyltransferase-mediated UTP end labeling. Furthermore,
      immunostaining of tumor specimens demonstrated in vivo accumulation of p21WAF1
      and p27KIP1 after CEP1612 treatment. The results suggest that CEP1612 is a
      promising candidate for further development as an anticancer drug and demonstrate
      the feasibility of using proteasome inhibitors as novel antitumor agents.

PMID- 11245421
TI  - Cytokine gene expression in neoplastic B cells from human mantle cell,
      follicular, and marginal zone lymphomas and in their postulated normal
      counterparts.
AB  - Cytokines may promote tumor growth by paracrine and/or autocrine pathways. Little
      information is available because malignant cells differ from their normal
      counterparts for the cytokine repertoire they express. Here we have investigated
      by reverse transcription-PCR the expression of 22 cytokine genes in neoplastic B
      lymphocytes from six patients with mantle cell lymphoma, 10 with follicular
      lymphoma, and 5 with marginal zone lymphoma and in their normal counterparts,
      i.e., naive, germinal center, and memory B cells, purified from tonsils. The
      overall profiles of cytokine gene expression in neoplastic B cells and in the
      corresponding normal B-cell subsets were similar, but some "holes" in the
      repertoire of malignant versus normal B lymphocytes were detected. Different
      "hole" combinations were identified consistently in mantle cell lymphoma,
      follicular lymphoma, and marginal zone lymphoma, thus representing molecular
      fingerprints of each individual lymphoma entity.

PMID- 11245423
TI  - Invasiveness of cutaneous malignant melanoma is influenced by matrix
      metalloproteinase 1 gene polymorphism.
AB  - The matrix metalloproteinases (MMPs) are implicated in connective tissue
      destruction during cancer invasion and metastasis. A naturally occurring variant
      arising from the insertion or deletion of a guanine in the promoter of the MMP-1
      gene has recently been reported and shown to influence its transcriptional
      activity in melanoma cells. In this study, MMP-1 genotype was determined in 139
      Caucasian patients with cutaneous malignant melanoma. The insertion allele was
      associated with deep invasive, and therefore poorer-prognosis, primary tumors
      [(34% of patients with vertical growth phase tumor were homozygous for the
      insertion allele compared with 17% of patients with horizontal growth phase tumor
      (P = 0.0333; odds ratio = 2.51)]. These data suggest that the invasiveness of
      cutaneous malignant melanoma is influenced by variation in the MMP-1 gene
      promoter that affects MMP-1 expression.

PMID- 11245422
TI  - Ovarian epithelial cell lineage-specific gene expression using the promoter of a
      retrovirus-like element.
AB  - We have isolated 462 bp of sequence termed ovarian-specific promoter 1 (OSP-1)
      that is part of a retrovirus-like element specifically expressed in the rat
      ovary. We have evaluated the ability of OSP-1 to activate gene expression in
      normal and neoplastic cell lines derived from the ovaries of rats and women. We
      have found that there was marked specificity in the ability of OSP-1 to drive
      reporter gene expression in an ovarian epithelial cell lineage manner. The
      expression of herpes simplex virus thymidine kinase (HSV-TK) under OSP-1 control
      was sufficiently ovarian cancer cell line specific to render ganciclovir
      approximately 50-fold more toxic in the A2780 human ovarian cancer cell line
      compared with clones of the HCT-116 and HT-29 colon cancer cell lines.
      Furthermore, ganciclovir had marked antitumor efficacy in vivo in severe combined
      immunodeficient mice bearing A2780OSP-1-HSV-TK as a s.c. xenograft. We suggest
      that these data support the use of OSP-1 as a tool to provide specificity to the
      gene therapy of ovarian cancer and to drive ovarian-specific oncogene expression
      for the creation of transgenic mouse models of ovarian cancer.

PMID- 11245424
TI  - Detection of mitochondrial DNA mutations in pancreatic cancer offers a "mass"-ive
      advantage over detection of nuclear DNA mutations.
AB  - We sequenced the complete 16.5-kb mitochondrial genome (mtDNA) in 15 pancreatic
      cancer cell lines and xenografts. Homoplasmic mtDNA somatic mutations and novel
      variants were identified in nearly all samples. Southern blot analysis and direct
      sequencing of mutation sites showed that the intracellular mass of mtDNA was
      greatly (6-8-fold) increased in pancreatic cancer cells in relation to
      corresponding normal cells; this property accounted for and greatly facilitated
      the identification of these mutations among the dense desmoplastic host reaction
      characteristic of primary pancreatic cancers. Structural characteristics and
      mathematical modeling of the evolution of mtDNA mutations suggested that many of
      the mutations identified might represent a random evolution of homoplasmic
      variants, rather than necessarily being a product of selective pressures.
      Complete sequencing of the nuclear MnSOD gene, which protects cells from the
      mitogenic and toxic effects of oxygen radicals, did not reveal any mutations.
      Nevertheless, the nearly ubiquitous prevalence and high copy number of mtDNA
      mutations suggest that they be considered of promising clinical utility in
      diagnostic applications.

PMID- 11245425
TI  - Epistatic interactions between skin tumor modifier loci in interspecific
      (spretus/musculus) backcross mice.
AB  - The development of cancer is influenced both by exposure to environmental
      carcinogens and by the host genetic background. Epistatic interactions between
      genes are important in determining phenotype in plant and animal systems and are
      likely to be major contributors to cancer susceptibility in humans. Several tumor
      modifier loci have been identified from studies of mouse models of human cancer,
      and genetic interactions between modifier loci have been detected by genome
      scanning using recombinant congenic strains of mice (R. Fijneman et al., Nat.
      Genet., 14: 465-467, 1996; T. van Wezel et al., Nat. Genet., 14: 468-470, 1996;
      W. N. Frankel et al., Nat. Genet., 14, 371-373, 1996). We demonstrate here that
      strong genetic interactions between skin tumor modifier loci can be detected by
      hierarchical whole genome scanning of a complete interspecific backcross [outbred
      Mus spretus X Mus musculus (NIH/Ola)]. A locus on chromosome 7 (Skts1) showed a
      highly significant interaction with Skts5 on chromosome 12 (P < 10(-16)), whereas
      additional significant interactions were detected between loci on chromosomes 4
      and 5, and 16 and 15. Some of these quantitative trait loci and their
      interactions, in particular the Skts1-Skts5 interaction, were confirmed in two
      completely independent backcrosses using inbred spretus strains (SEG/Pas and
      SPRET/Ei) and NIH/Ola. These results, therefore, illustrate the general use of
      interspecific crosses between Mus musculus and Mus spretus for the detection of
      strong genetic interactions between tumor modifier genes.

PMID- 11245426
TI  - Chromosomal alterations in lung adenocarcinoma from smokers and nonsmokers.
AB  - The etiology of lung tumors arising in nonsmokers remains unclear. Although
      mutations in the K-ras and p53 genes have been reported to be significantly
      higher in smoking-related lung carcinomas, in the present study we performed a
      more comprehensive analysis in search of additional genetic changes between lung
      adenocarcinoma from tobacco- and non-tobacco-exposed patients. We selected a
      matched cohort of 18 lifetime nonsmoking and 27 smoking patients diagnosed with
      primary adenocarcinoma of the lung and searched for chromosomal alterations in
      each tumor by testing normal and tumor tissue with 54 highly polymorphic
      microsatellite markers located on 28 different chromosomal arms. Allelic losses
      or gains at chromosomal arms 3p (37 versus 6%), 6q (46 versus 12%), 9p (65 versus
      22%), 16p (28 versus 0%), 17p (45 versus 11%), and 19p (58 versus 16%) were
      present significantly more often in adenocarcinomas from smokers than from
      nonsmokers. Chromosomal arms showing allelic imbalance in lung tumors from
      nonsmokers were rare but occurred more often at 19q (22%), 12p (22%), and 9p
      (22%). The FAL (fractional allelic loss or gain) is defined as the percentage of
      chromosomal arm losses/gains among the total informative chromosomal arms. Tumors
      from smokers harbored higher levels of FAL (13 (48%) of 27 showed FAL > or = 0.3)
      compared with the lung tumors from the nonsmoker patients (2 (11%) of 18 showed
      FAL > or = 0.3; P = 0.02; odds ratio, 0.13; 95% confidence interval, 0.01-0.79).
      Our data demonstrate that widespread chromosomal abnormalities are frequent in
      lung adenocarcinoma from smokers, whereas these abnormalities are infrequent in
      such tumors arising in nonsmokers. These observations support the notion that
      lung cancers in nonsmokers arise through genetic alterations distinct from the
      common events observed in tumors from smokers.

PMID- 11245427
TI  - Resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
      induced apoptosis in neuroblastoma cells correlates with a loss of caspase-8
      expression.
AB  - Disruption of apoptotic pathways may be involved in tumor formation, regression,
      and treatment resistance of neuroblastoma (NB). Tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL) is a potent inducer of apoptosis in cancer cell
      lines, whereas normal cells are not sensitive to TRAIL-mediated apoptosis. In
      this study we analyzed the expression and function of TRAIL and its agonistic and
      antagonistic receptors as well as expression of cellular FLICE-like inhibitory
      protein and caspase-2, -3, -8, -9, and -10 in 18 NB cell lines. Semiquantitative
      RT-PCR revealed that TRAIL-R2 and TRAIL-R3 are the main TRAIL-receptors used by
      NB cells. Sensitivity to TRAIL-induced apoptosis did not correlate with mRNA
      expression of TRAIL receptors or cellular FLICE-like inhibitory protein.
      Surprisingly, caspase-8 and caspase-10 mRNA expression was detected in only 5 of
      18 NB cell lines. Interestingly, only these five NB cell lines were susceptible
      to TRAIL-induced apoptosis in a time- and dose-dependent manner. Treatment with 5
      aza-2'-deoxycytidine restored mRNA and protein expression of caspase-8 and TRAIL
      sensitivity of resistant cell lines, suggesting that gene methylation is involved
      in caspase inactivation. The TRAIL system seems to be functional in NB cells
      expressing caspase-8 and/or caspase-10. Because many cytotoxic drugs induce
      caspase-dependent apoptosis, failure to express caspase-8 and/or caspase-10 might
      be an important mechanism of resistance to chemotherapy in NB.

PMID- 11245428
TI  - Breast stroma plays a dominant regulatory role in breast epithelial growth and
      differentiation: implications for tumor development and progression.
AB  - Although growth factors and extracellular matrix (ECM) are recognized as
      important contributors to breast epithelial growth, morphogenesis, hormone
      responsiveness, and neoplastic progression, the influence of functional
      interactions between breast stromal and epithelial cells on these processes has
      not been defined. Using a novel three-dimensional cell-cell interaction model, we
      have compared the abilities of different mesenchymal cell types, including breast
      fibroblasts derived from reduction mammoplasty and tumor tissues, and human
      umbilical endothelial cells (HUVECs) to induce three-dimensional morphogenesis
      and growth of normal MCF10A and preneoplastic MCF10AT1-EIII8 (referred as EIII8)
      human breast epithelial cells. Our data demonstrate a requirement for
      organspecific fibroblasts in the induction of epithelial morphogenesis. Whereas
      inclusion of normal reduction mammoplasty fibroblasts inhibit or retard
      morphological conversion and growth of MCF10A and EIII8 cells, respectively,
      tumor-derived breast fibroblasts evoke ductal-alveolar morphogenesis of both
      MCF10A and EIII8 cells. The growth and morphogenesis inhibitory effects of normal
      fibroblasts remain even in the presence of estrogen because they are able to
      suppress the estrogen-induced growth of EIII8 cells, whereas tumor fibroblasts
      support and maintain estrogen responsiveness of EIII8 cells. The inductive
      morphogenic effects of tumor fibroblasts on EIII8 cells is further augmented by
      the inclusion of HUVECs because these cocultures undergo a dramatic increase in
      proliferation and branching ductal-alveolar morphogenesis that is accompanied by
      an increase in invasion, degradation of coincident ECM, and expression of MMP-9.
      Therefore, tumor fibroblasts confer morphogenic and mitogenic induction of
      epithelial cells, and further enhancement of growth and progression requires
      active angiogenesis. These data illustrate the importance of structural and
      functional interactions between breast stromal and epithelial cells in the
      regulation of breast epithelial growth and progression.

PMID- 11245429
TI  - DNA methyltransferase inhibition enhances apoptosis induced by histone
      deacetylase inhibitors.
AB  - Histone acetylation has long been associated with transcriptional activation,
      whereas conversely, deacetylation of histones is associated with gene silencing
      and transcriptional repression. Here we report that inhibitors of histone
      deacetylase (HDAC), depsipeptide and trichostatin A, induce apoptotic cell death
      in human lung cancer cells as demonstrated by DNA flow cytometry and Western
      immunoblot to detect cleavage of poly(ADP-ribose) polymerase. This HDAC
      inhibitorinduced apoptosis is greatly enhanced in the presence of the DNA
      methyltransferase inhibitor, 5-aza-2'-deoxycytidine (DAC). The HDAC inhibitor
      induced apoptosis appears to be p53 independent, because no change in apoptotic
      cell death was observed in H1299 cells that expressed exogenous wild-type p53
      (H1299 cells express no endogenous p53 protein). To further investigate the
      mechanism of DAC-enhanced, HDAC inhibitor-induced apoptosis, we analyzed histone
      H3 and H4 acetylation by Western immunoblotting. Results showed that depsipeptide
      induced a dose-dependent acetylation of histones H3 and H4, which was greatly
      increased in DAC-pretreated cells. By analyzing the acetylation of specific
      lysine residues at the amino terminus of histone H4 (Ac-5, Ac-8, Ac-12, and Ac
      16), we found that the enhancement of HDAC inhibitor-induced acetylation of
      histones in the DAC-pretreated cells was not lysine site specific. These results
      demonstrate that DNA methylation status is an important determinant of apoptotic
      susceptibility to HDAC inhibitors.

PMID- 11245430
TI  - Global effects of anchorage on gene expression during mammary carcinoma cell
      growth reveal role of tumor necrosis factor-related apoptosis-inducing ligand in
      anoikis.
AB  - Anchorage-independent growth is a hallmark of tumor cells. We compared gene
      expression profiles of anchored and nonanchored human mammary carcinoma cells to
      study this phenomenon. In this study, we show that anchorage had striking effects
      on cell growth and morphology but altered transcript levels from a limited number
      of genes. Only about 1% of mRNA transcripts detected in these cells was altered
      by anchorage. These include genes related to amino acid and polyamine metabolism,
      apoptosis, ion channels, cytoskeletal and stress proteins, transcription factors,
      and growth factors. Some of these may be crucial for the survival of transformed
      cells. For example, clusterin and the tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL) were suppressed by anchorage, which could help prevent
      programmed cell death of these tumor cells. In addition to suppressing TRAIL
      expression, anchorage also decreased the susceptibility of these tumor cells to
      TRAIL-induced apoptosis as determined by poly(ADP-ribose) phosphorylase cleavage,
      annexin-V binding (P < 0.01), and cell cycle analysis (P < 0.0001). These data
      may help explain mechanisms by which anchorage prevents apoptosis of cells that
      would otherwise experience anoikis. Thus, genes found to be altered by this
      analysis could serve as potential targets for anticancer therapy. These findings
      suggest that TRAIL may be used as a means to target circulating epithelial tumor
      cells before their attachment and colonization at new sites.

PMID- 11245431
TI  - Down-regulation of promoter 1.3 activity of the human aromatase gene in breast
      tissue by zinc-finger protein, snail (SnaH).
AB  - Aromatase (estrogen synthetase) is expressed in breast cancer tissue, and in situ
      expression of the enzyme stimulates breast cancer growth. Promoter I.3 is one of
      the major promoters that control the expression of aromatase in breast cancer
      tissue. Using the yeast one-hybrid approach to screen a human breast tissue
      hybrid cDNA expression library, we found that the zinc-finger transcriptional
      factor Snail (SnaH) interacted with a regulatory region near promoter I.3 of the
      human aromatase gene. DNA mobility shift assays and mutation analyses using
      recombinant SnaH protein expressed in Escherichia coli have revealed that this
      protein interacts with a segment, 5'-CTGATGAAGT-3', which is between 66 and 76 bp
      upstream from the transcriptional start site of promoter I.3. Using mammalian
      cell transfection experiments, SnaH was found to act as a repressor of promoter
      I.3 activity. Site-directed mutagenesis experiments have revealed that the NH2
      terminal SNAG domain is important for the repressor activity of SnaH. To
      demonstrate the inhibitory activity against aromatase expression, a stable SnaH
      expressing MDA-MB-231 breast cancer cell line was generated, and the aromatase
      RNA messages in the SnaH-transfected cell line were found to be 30% of those in
      the vector-transfected cell line. Reverse transcription-PCR analysis on RNAs
      isolated from 12 cell lines has confirmed that SnaH is expressed at a higher
      level in normal breast epithelial cell and stromal fibroblast cell lines than in
      breast cancer cell lines. In addition, SnaH mRNA was detected in only 16 of 55
      breast cancer specimens. On the other hand, aromatase mRNA was detected in 54 of
      the 55 specimens. Our results indicate that SnaH acts as a repressor that down
      regulates the expression of aromatase in normal breast tissue by suppressing the
      function of promoter I.3. A reduction of the expression of SnaH in breast cancer
      tissue further suggests a cancer-protective role for this protein in normal
      breast tissue.

PMID- 11245432
TI  - Phosphorylation- and Skp1-independent in vitro ubiquitination of E2F1 by multiple
      ROC-cullin ligases.
AB  - Ubiquitin-dependent proteolysis plays a critical role in the control of many
      cellular processes and is mediated by a cascade of enzymes involving ubiquitin
      activating (El), conjugating (E2), and ligating (E3) activities. Cullin 1/CDC53
      functions as an E3 ligase by interacting with RING finger protein ROC1 and
      recruiting phosphorylated substrate. We report here that E2F1 transcription
      factor can be ubiquitinated in vitro and in vivo by multiple ROC-cullin ligases.
      In vitro, E2F1 can be ubiquitinated by E2/Ubc5 but not by E2/CDC34, is dependent
      on catalytically active ROC1, and is protected by the Rb protein. In contrast to
      substrates of the SKP1-Cullin 1-F box (SCF) complexes, in vitro ubiquitination of
      E2F1 by CUL1-ROC1 ligase does not require E2F1 phosphorylation, is not stimulated
      by overexpression of F box protein SKP2, and is not affected by immunodepletion
      of SKP1 or mutations in CUL1 disrupting SKPI binding. These results suggest a
      novel, SKP1-independent mechanism for targeting E2F1 ubiquitination.

PMID- 11245433
TI  - Modulation of nucleotide excision repair capacity by XPD polymorphisms in lung
      cancer patients.
AB  - Sequence variations have been identified in a number of DNA repair genes,
      including XPD, but the effect of these polymorphisms on DNA repair capacity (DRC)
      is uncertain. We therefore examined XPD polymorphisms at Lys751Gln and Asp312Asn
      in 341 white lung cancer cases and 360 age-, sex-, ethnicity-, and smoking
      matched controls accrued in a hospital-based molecular epidemiological study of
      susceptibility markers for lung cancer. As previously reported, DRC was
      statistically significantly lower in the cases than in the controls (7.8% versus
      9.5%; P < 0.001), which represents an average 18% reduction among the cases. The
      variant Lys751Gln and Asp312Asn allele frequencies were 0.36 and 0.29,
      respectively, for the cases and 0.33 and 0.27, respectively, for the controls.
      For subjects homozygous for the variant genotype at either locus, the adjusted
      odds ratio [95% confidence interval (CI)] was 1.84 (1.11-3.04; P = 0.018, for
      trend). Both cases and controls with the wild-type genotypes exhibited the most
      proficient DRC. The risk (95% CI) for suboptimal DRC (defined as less than the
      median DRC value among the controls) was 1.57 (0.74-3.35) for those with the
      Gln/Gln751 genotype. For cases with the Asn/Asn312 genotype, the risk (95% CI)
      was 3.50 (1.06-11.59). For cases who were homozygous at either locus, the risk
      was 2.29 (1.03-5.12; P = 0.048, for trend). The pattern was less evident among
      the controls, although there was a nonsignificant 41% increase in the risk of
      suboptimal DRC for controls who were homozygous at either locus. These results
      suggest that the two XPD polymorphisms have a modulating effect on DRC,
      especially in the cases.

PMID- 11245434
TI  - Erythropoietin restores the anemia-induced reduction in cyclophosphamide
      cytotoxicity in rat tumors.
AB  - The aim of this study was to examine the impact of anemia prevention by
      recombinant human erythropoietin (rHuEPO) treatment on the cytotoxicity of
      cyclophosphamide in solid experimental tumors. Anemia was induced using a single
      dose of carboplatin (50 mg/kg i.v.) resulting in a long-lasting reduction (30%)
      of the hemoglobin concentration. In a second group, the development of anemia was
      prevented by rHuEPO (1000 IU/kg) administered s.c. three times/week starting 7
      days before carboplatin application. Four days after carboplatin treatment,
      tumors (DS-sarcoma of the rat) were implanted s.c. onto the hind food dorsum.
      Neither carboplatin nor rHuEPO treatment influenced tumor growth rate per se.
      When tumors were treated with a single dose of cyclophosphamide (60 mg/kg i.p.) 5
      days after implantation, a growth delay with a subsequent regrowth of the tumors
      was observed. In the anemia group, the growth delay was significantly shorter
      compared with nonanemic controls (13.3 days versus 8.6 days). In the group where
      anemia was prevented by rHuEPO treatment, growth delay was comparable with that
      of nonanemic controls (13.3 days). These results suggest that chemotherapy
      induced anemia reduces cytotoxicity of cyclophosphamide in tumors, whereas
      correction of anemia by rHuEPO treatment (epoetin alpha) increases the
      sensitivity, probably as a result of an improved oxygen supply to tumor tissue.

PMID- 11245435
TI  - Altered profiles in nuclear matrix proteins associated with DNA in situ during
      progression of breast cancer cells.
AB  - Nuclear matrix proteins (NMPs) show promise as informative biomarkers in
      following the pathogenesis of breast cancer. The nuclear matrix is a dynamic RNA
      protein network involved in the organization and expression of chromatin.
      Cisplatin, which preferentially cross-links nuclear matrix proteins to DNA in
      situ, may be used to identify NMPs that organize and/or regulate the processing
      of DNA. In this study, we analyzed the nuclear matrix proteins from an estrogen
      receptor-positive breast cancer cell line panel consisting of MCF-7, MIII, LCC1,
      and LCC2 cell lines. This cell line panel reflects the stages of malignant
      progression in breast cancer. Proteins isolated from nuclear matrices and
      proteins cross-linked to nuclear DNA in situ with cisplatin were analyzed by two
      dimensional gel electrophoresis. Specific changes in nuclear matrix proteins
      bound to nuclear DNA were identified. In concordance with estrogen independence
      and antiestrogen insensitivity, a loss in cisplatin cross-linking of specific
      NMPs to nuclear DNA was observed. Our results suggest that progression of breast
      cancer is accompanied by a reorganization of chromosomal domains, which may lead
      to alterations in gene expression.

PMID- 11245436
TI  - Up-regulation of urokinase-type plasminogen activator by insulin-like growth
      factor-I depends upon phosphatidylinositol-3 kinase and mitogen-activated protein
      kinase kinase.
AB  - Elevated levels of urokinase plasminogen activator-1 (uPA) and the insulin-like
      growth factor-I receptor (IGF-IR) are associated with breast cancer recurrence
      and decreased survival. It is possible that activation of IGF-IR and elevations
      in uPA are mechanistically linked. Our laboratory recently showed that insulin
      like growth factor-I (IGF-I) induces uPA protein and mRNA in the breast cancer
      cell line MDA-MB-231. We also found that IGF-IR and uPA were commonly
      overexpressed in primary breast cancers. In this study, we investigated the
      signal transduction pathway through which IGF-I regulates uPA.
      Phosphatidylinositol 3-kinase, mitogen-activated protein kinase kinase, and p70
      kinase were inhibited with LY294002, PD98059, and rapamycin, respectively.
      Induction of uPA protein by IGF-I was partially inhibited by LY294002 (60%
      inhibition) or PD98059 (30% inhibition) but not by rapamycin. The production of
      uPA protein induced by IGF-I was blocked up to 90% by the tyrosine kinase
      inhibitor herbimycin A. Furthermore, herbimycin A suppressed the phosphorylation
      of AKT and Erk1/2. Next, we tested the impact of the signal transduction
      inhibitors on uPA gene expression. Both LY294002 and PD98059 were required to
      completely inhibit uPA mRNA expression, whereas each drug alone resulted in
      approximately 50% reduction in uPA expression. Next, using a minimal uPA
      luciferase promoter construct containing the binding sites for the AP-1 and Ets
      transcription factors, we observed that IGF-I stimulated the uPA promoter via
      these sites. Furthermore, both Ly294002 and PD98059 were necessary to block IGF-I
      stimulated uPA-Luc activity. In summary, we conclude that IGF-I requires both
      phosphatidylinositol 3-kinase and mitogen-activated protein kinase kinase
      dependent pathways to optimally induce uPA expression. These findings suggest
      that the development of drugs targeting these pathways may benefit breast cancer
      patients at a high risk of recurrence, such as those who have primary tumors
      overexpressing IGF-IR and uPA.

PMID- 11245437
TI  - Elevated protein kinase C betaII is an early promotive event in colon
      carcinogenesis.
AB  - Protein kinase C (PKC) has been implicated in colon carcinogenesis in humans and
      in rodent models. However, little is known about the specific role of individual
      PKC isozymes in this process. We recently demonstrated that elevated expression
      of PKC betaII in the colonic epithelium induces hyperproliferation in vivo (N. R.
      Murray et al., J. Cell Biol., 145: 699-711, 1999). Because hyperproliferation is
      a major risk factor for colon cancer, we assessed whether specific alterations in
      PKC betaII expression occur during azoxymethane-induced colon carcinogenesis in
      mice. An increase in PKC betaII expression was observed in preneoplastic lesions
      (aberrant crypt foci, 3.7-fold) compared with saline-treated animals, and in
      colon tumors (7.8-fold; P = 0.011) compared with uninvolved colonic epithelium.
      In contrast, PKC alpha and PKC betaI (a splicing variant of PKC betaII)
      expression was slightly decreased in aberrant crypt foci and dramatically reduced
      in colon tumors. Quantitative reverse transcription-PCR analysis revealed that
      PKC mRNA levels do not directly correlate with PKC protein levels, indicating
      that PKC isozyme expression is likely regulated at the
      posttranscriptional/translational level. Finally, transgenic mice expressing
      elevated PKC betaII in the colonic epithelium exhibit a trend toward increased
      colon tumor formation after exposure to azoxymethane. Taken together, our results
      demonstrate that elevated expression of PKC betaII is an important early,
      promotive event that plays a role in colon cancer development.

PMID- 11245438
TI  - Frequent mutations of Fas gene in thyroid lymphoma.
AB  - Fas (Apo-1/CD95) is a cell-surface receptor involved in cell death signaling
      through binding of Fas ligand. Mutation of the Fas gene results in accumulation
      of lymphoid cells and thus might contribute to lymphomagenesis. Thyroid lymphoma
      (TL) is supposed to arise from active lymphoid cells formed in the preceding
      autoimmune chronic lymphocytic thyroiditis (CLTH). We examined the open reading
      frame of Fas cDNA in 11 cases of CLTH and 26 cases of TL. These patients were
      admitted to the hospital with varying degrees of goiter. All of the CLTH patients
      were female, with median age of 65 years, and all but five cases of TL were
      female, with median age of 61 years. Mutations of the Fas gene were detected in 3
      (27.3%) of 11 cases of CLTH and 17 (65.4%) of 26 of TL. The Fas mutations
      comprised 18 frameshift, 3 missense, and 1 nonsense mutation. Frameshift
      mutations were caused by insertion of 1 bp (A) at nucleotide 1095 in 10 cases and
      by lack of exon 8 in 8 cases. The insertion of 1 bp (A) at nucleotide 1095 has
      never been reported in other kinds of malignancies. Thus, this might be unique in
      TL and CLTH and might be mutational hotspots in these diseases. All mutations
      occurred in the cytoplasmic region (death domain) known to be involved in the
      apoptotic signal transduction and thus could be loss-of-function mutations. These
      findings suggested that accumulation of lymphoid cells in CLTH with Fas mutation
      provides a basis for development of TL.

PMID- 11245440
TI  - Involvement of mammalian MLH1 in the apoptotic response to peroxide-induced
      oxidative stress.
AB  - MLH1 is an integral part of the mismatch repair complex, and the loss of this
      protein is associated with the acquisition of a mutator phenotype, microsatellite
      instability, and a predisposition to cancer. Deficiencies in the mismatch repair
      complex, including the loss of MLH1, result in elevated resistance to specific
      inducers of DNA damage, yet the mechanisms involved in this DNA-damage resistance
      are largely unknown. Abnormal cellular responses to DNA damage can lead to the
      selection of cells with a greater propensity for neoplastic transformation and
      might also reduce the effectiveness of certain chemotherapeutic drugs. It is
      therefore important to identify agents that provide selective pressure for growth
      of MLH1-deficient cells and to characterize further the pathways involved. In
      this study, we show that both human epithelial and mouse embryo fibroblast cell
      lines lacking the MLH1 protein are more resistant to two inducers of oxidative
      stress, hydrogen peroxide and tert-butyl hydroperoxide. Our analyses suggest that
      the observed differences in cellular viability are mediated primarily through
      apoptotic pathways and not through deficiencies in cell cycle checkpoint
      controls. Additional characterization of the signaling pathways for hydrogen
      peroxide-induced apoptosis in MLH1-proficient cells demonstrates the involvement
      of increased mitochondrial permeability, the release of cytochrome c, and caspase
      3 activation. Together, our data indicate that cells lacking MLH1 may possess a
      selective growth advantage under oxidatively stressed conditions via the
      disregulation of apoptosis, possibly involving the mitochondria.

PMID- 11245439
TI  - Suppression of tumor cell growth both in nude mice and in culture by n-3
      polyunsaturated fatty acids: mediation through cyclooxygenase-independent
      pathways.
AB  - Dietary n-3 polyunsaturated fatty acids (PUFAs), as compared with n-6 PUFAs,
      suppress cellular production of prostaglandins and tumor cell growth both in
      vitro and in vivo. However, the mechanism by which n-3 PUFAs suppress tumor
      growth is not understood. We investigated whether the suppression of tumor cell
      growth by dietary n-3 PUFAs is mediated through inhibition of cyclooxygenase
      (COX). A colon tumor cell line, HCT-116, that does not express COX was stably
      transfected with the constitutively expressed COX-1 or the inducible COX-2 cDNA
      using a retroviral transfection and infection system. Athymic nude mice
      transplanted with the cells expressing enzymatically active COX were fed
      isocaloric diets containing either safflower oil or fish oil for 2 weeks before
      the start of the experiment and for an additional 21 days after transplantation.
      Both tumor volume and tumor burden (tumor volume/body weight) were significantly
      reduced in mice fed the fish oil diet as compared with safflower oil-fed mice.
      This reduction occurred even in control mice that received injections with cells
      infected with the retroviral vector without COX-1 or COX-2 cDNA. The growth of
      tumor cells expressing COX was not different from the growth of those transfected
      with the vector alone in the nude mice and in soft agar. N-3 PUFAs, as compared
      with linoleic acid, also inhibited the growth of these cells in culture. This
      growth inhibition by n-3 PUFAs was not affected by COX-1 or COX-2 overexpression.
      Contrary to general belief, these results indicate that the suppression of tumor
      growth by dietary n-3 PUFAs is mediated through COX-independent pathways.

PMID- 11245441
TI  - Crkl enhances leukemogenesis in BCR/ABL P190 transgenic mice.
AB  - The adapter protein Crkl has been implicated in the abnormal signal transduction
      pathways activated by the Bcr/Abl oncoprotein, which causes Philadelphia-positive
      leukemias in humans. To investigate the role of Crkl in tumorigenesis, we have
      generated transgenic mice that express human Crkl from the CRKL promoter. Western
      blot analysis showed a 4-6-fold overexpression of transgenic Crkl above
      endogenous crkl in two lines and increased constitutive complex formation between
      Crkl and C3G, an exchange factor for the small GTPase Rap1. This was associated
      with a significant increase in integrin-based motility of transgenic macrophages.
      Overexpression of Crkl was associated with increased incidence of tumor
      formation, and Rap1 was activated in a metastatic mammary carcinoma. The
      coexpression of Crkl and Bcr/Abl in mice transgenic for P190 BCR/ABL and CRKL
      markedly increased the rapidity of development of leukemia/lymphoma, decreasing
      the average survival by 3.8 months. These results provide direct evidence that
      Crkl plays a role in tumor development and is important in the leukemogenesis
      caused by Bcr/Abl.

PMID- 11245442
TI  - Increased gastric epithelial cell apoptosis associated with colonization with
      cagA + Helicobacter pylori strains.
AB  - Gastric colonization by Helicobacter pylori is a risk factor for noncardia
      gastric cancer. The association between H. pylori and cancer may be attributable
      to increased epithelial cell turnover, possibly related to antigastric
      antibodies. Two previous studies reported a disproportionate increase in
      proliferation relative to apoptosis in patients with H. pylori strains expressing
      the virulence-related cagA gene. This has led to the hypothesis that an
      abrogation of apoptosis by cagA-positive strains may promote neoplasia. We,
      therefore, examined the effect of H. pylori on gastric epithelial proliferation,
      apoptosis, and the presence of serum antiparietal cell antibodies in a large
      prospective study. Proliferation and apoptosis were evaluated "blindly" using
      validated immunohistochemical methods in two antral and two gastric corpus
      biopsies from 60 patients with nonulcer dyspepsia, and results were correlated
      with the presence of serum antiparietal cell antibodies. H. pylori colonization
      was assessed by histology, biopsy urease test, and serology. Proliferation was
      increased 2-fold in both antrum and corpus in H. pylori-positive patients, was
      not related to H. pylori cagA status, and was positively correlated with
      histological gastritis. Apoptosis was increased in the antrum and body only in
      patients with cagA-positive H. pylori strains. Antiparietal cell antibodies were
      not more prevalent in H. pylori colonization, and their presence was inversely
      related to epithelial apoptosis scores we therefore conclude that in patients
      with nonulcer dyspepsia, H. pylori carriage is associated with increased
      proliferation. Futhermore the cag pathogenicity island is associated with
      increased apoptosis. Our results do not support the hypothesis that there is a
      relative deficiency of gastric epithelial cell apoptosis associated with the
      carriage of cagA-positive strains. Host factors may be more important than
      bacterial products in determining the long-term outcome of H. pylori
      colonization.

PMID- 11245443
TI  - P-Glycoprotein and multidrug resistance-related protein expressions in relation
      to technetium-99m methoxyisobutylisonitrile scintimammography findings.
AB  - The purpose of this study was to retrospectively study 48 patients with
      infiltrating ductal breast cancer to evaluate the relationship between the degree
      of accumulation of technetium-99m methoxyisobutylisonitrile (Tc-MIBI) and P
      glycoprotein (Pgp) or multidrug resistance-related protein (MRP) expression in
      breast cancer tissues. Before surgery or biopsy, all 48 patients underwent
      scintimammography started 10 min after the injection of Tc-MIBI. Tumor:background
      (T:B) ratios were calculated from the Tc-MIBI scintimammography.
      Immunohistochemical analysis was performed on the pathological specimens of the
      48 breast tumors to determine Pgp and MRP expression. According to the results of
      immunohistochemical analysis, the 48 breast cancers were separated into four
      groups: (a) group 1, 12 cancers with both positive Pgp expression and positive
      MRP expression; (b) group 2, 12 cancers with positive Pgp expression and negative
      MRP expression; (c) group 3, 12 cancers with negative Pgp expression and positive
      MRP expression; and (d) group 4, 12 cancers with both negative Pgp expression and
      negative MRP expression. Among the four groups, the T:B ratio was lowest in group
      1 (1.13+/-0.10) and highest in group 4 (2.17+/-0.14), respectively (P < 0.05).
      The T:B ratios of groups 2 (1.30+/-0.25) and 3 (1.32+/-0.26) were between those
      of groups 1 and 4. Our data confirmed that Tc-MIBI scintimammography is useful
      for determining Pgp and MRP expression in patients with breast cancers.

PMID- 11245444
TI  - The COOH-terminal Src kinase Csk is a tumor antigen in human carcinoma.
AB  - The cytoplasmic tyrosine kinase cSrc is involved in the regulation of many
      important cellular functions including cell growth and transformation, and its
      activity is down-regulated by phosphorylation of the Tyr530 residue by the COOH
      terminal Src tyrosine kinase, Csk. Because cSrc was previously found
      overexpressed, activated, and in some cases mutated in carcinoma, we investigated
      whether it could act as a tumor antigen. We show that whereas no autoantibodies
      were found against cSrc or its relative Fyn, up to 20% of patients with carcinoma
      had high-affinity autoantibodies against Csk. Immunity mainly resulted from a
      secondary response, as indicated by the presence of IgG1 in the sera. Antibodies
      were linked to the cancer because they were not detected in healthy subjects nor
      in patients with unrelated diseases, and their levels decreased in the sera of
      patients after surgical resection. Furthermore, they behaved as early markers of
      epithelial transformation because they were present in sera of patients with
      early-stage tumors and precancerous lesions such as colorectal polyps and in sera
      of patients that were scored negative for other cancer serological markers (CEA,
      CA15-3, CA19-9, p53 antibodies). Finally the presence of these antibodies was
      attributed, at least in part, to a substantial elevation of Csk protein levels in
      the corresponding tumors. However a strong increase in Src activity was also
      observed in these tissues, which suggested that Csk cannot regulate Src-like
      activity in carcinoma. Taken together, these data demonstrate that Csk acts as an
      autoantigen, and the detection of anti-Csk antibodies may have potential
      diagnostic usefulness in the early detection and postoperative follow-up of
      patients with carcinoma.

PMID- 11245445
TI  - Thymidine kinase and thymidylate synthase in advanced breast cancer: response to
      tamoxifen and chemotherapy.
AB  - Thymidylate synthase (TS) is a crucial target for 5-fluorouracil (5-FU) in the de
      novo pathway of pyrimidine synthesis, which is necessary for DNA synthesis.
      Thymidine kinase (TK) plays a key role in the complementary or alternative
      salvage pathway of pyrimidine synthesis in acute or pathological tissue stress.
      In the present study, the activity levels of TS and TK were determined in 257
      primary breast tumors of patients who received tamoxifen as first-line systemic
      therapy after diagnosis of advanced disease. In 155 (60%) responding patients,
      the median response duration was 23 months for tumors with low TK activity, 15
      months for tumors with intermediate TK activity, and 13 months for tumors with
      high TK activity (P = 0.003). In Cox multivariate analysis corrected for
      classical predictive factors including estrogen receptor and progesterone
      receptor, patients with intermediate and high levels of TK activity in their
      tumors showed a rapid disease progression (P = 0.0002) and an early death (P =
      0.002) after start of tamoxifen treatment. Tumor TS activity levels were not
      significantly associated with the efficacy of tamoxifen treatment. In 121
      patients who became resistant to tamoxifen or additional endocrine treatments and
      who received 5-FU-containing polychemotherapy, tumor TK activity was not
      significantly related to the efficacy of chemotherapy. Of the 13 patients with
      low tumor TS activity, only 1 (8%) responded favorably, whereas 46% (43 of 93) of
      those with intermediate and 73% (11 of 15) of those with high TS activity
      responded (P = 0.001). In Cox multivariate regression analysis in which TS was
      the only significant variable, intermediate and high TS activities were
      associated with a slow disease progression (P = 0.005) and prolonged survival (P
      = 0.016) on chemotherapy. In conclusion, for patients with recurrent breast
      cancer, high tumor TK activity is a significant marker of poor clinical outcome
      on tamoxifen therapy. Elevated tumor TS activity predicts a favorable outcome for
      5-FU-containing polychemotherapy when applied after tumor progression on
      endocrine therapy.

PMID- 11245446
TI  - Increased in vivo phosphorylation of ret tyrosine 1062 is a potential
      pathogenetic mechanism of multiple endocrine neoplasia type 2B.
AB  - Mutations of the Ret receptor tyrosine kinase are responsible for inheritance of
      multiple endocrine neoplasia (MEN2A and MEN2B) and familial medullary thyroid
      carcinoma syndromes. Although several familial medullary thyroid carcinoma and
      most MEN2A mutations involve substitutions of extracellular cysteine residues, in
      most MEN2B cases there is a methionine-to-threonine substitution at position 918
      (M918T) of the Ret kinase domain. The mechanism by which the MEN2B mutation
      converts Ret into a potent oncogene is poorly understood. Both MEN2A and MEN2B
      oncoproteins exert constitutive activation of the kinase. However, the highly
      aggressive MEN2B phenotype is not supported by higher levels of Ret-MEN2B kinase
      activity compared with Ret-MEN2A. It has been proposed that Ret-MEN2B is more
      than just an activated Ret kinase and that the M918T mutation, by targeting the
      kinase domain of Ret, might alter Ret substrate specificity, thus affecting Ret
      autophosphorylation sites and the ability of Ret to phosphorylate intracellular
      substrates. We show that the Ret-MEN2B mutation causes specific potentiated
      phosphorylation of tyrosine 1062 (Y1062) compared with Ret-MEN2A. Phosphorylated
      Y1062 is part of a Ret multiple effector docking site that mediates recruitment
      of the Shc adapter and of phosphatidylinositol-3 kinase (PI3K). Accordingly, we
      show that Ret-MEN2B is more active than Ret-MEN2A in associating with She and in
      causing constitutive activation of the Ras/mitogen-activated protein kinase and
      PI3K/Akt cascades. We conclude that the MEN2B mutation specifically potentiates
      the ability of Ret to autophosphorylate Y1062 and consequently to couple to the
      Ras/mitogen-activated protein kinase and the PI3K/Akt pathways. The more
      efficient triggering of these pathways may account for the difference between
      MEN2A and MEN2B syndromes.

PMID- 11245447
TI  - Role of the central melanocortin system in cachexia.
AB  - Individuals affected with either acute or chronic diseases often show disorders
      of nutrient balance. In some cases, a devastating state of malnutrition known as
      cachexia arises, brought about by a synergistic combination of a dramatic
      decrease in appetite and an increase in metabolism of fat and lean body mass.
      Stimulation of the hypothalamic melanocortin 4 receptor (MC4-R) produces relative
      anorexia and increased metabolic rate, even in a relatively starved state. Here
      we demonstrate that cachexia induced by lipopolysaccharide administration and by
      tumor growth is ameliorated by central MC4-R blockade. MC4-R knock-out mice or
      mice administered the MC3-R/MC4-R antagonist, agouti-related peptide, resist
      tumor-induced loss of lean body mass, and maintain normal circadian activity
      patterns during tumor growth. The final tumor mass is not affected in these
      animals, providing further support for the potential role of MC4-R antagonism in
      the treatment of cachexia in disease states.

PMID- 11245448
TI  - Vitamin D is a prooxidant in breast cancer cells.
AB  - The anticancer activity of the hormonal form of vitamin D, 1,25-dihydroxyvitamin
      D [1,25(OH)2D], is associated with inhibition of cell cycle progression,
      induction of differentiation, and apoptosis. In addition, 1,25(OH)2D3 augments
      the activity of anticancer agents that induce excessive reactive oxygen species
      generation in their target cells. This study aimed to find out whether
      1,25(OH)2D3, acting as a single agent, is a prooxidant in cancer cells. The ratio
      between oxidized and reduced glulathione and the oxidation-dependent inactivation
      of glyceraldehyde-3phosphate dehydrogenase (GAPDH) are considered independent
      markers of cellular reactive oxygen species homeostasis and redox state.
      Treatment of MCF-7 breast cancer cells with 1,25(OH)2D3 (10-100 nM for 24-48 h)
      brought about a maximal increase of 41+/-13% (mean +/- SE) in the
      oxidized/reduced glutathione ratio without affecting total glutathione levels.
      The in situ activity of glutathione peroxidase and catalase were not affected by
      1,25(OH)2D3, as assessed by the rate of H2O2 degradation by MCF-7 cell cultures.
      Neither did treatment with 1,25(OH)2D3 affect the levels of glutathione reductase
      or glutathione S-transferase as assayed in cell extracts. The hormone did not
      affect overall glutathione consumption and efflux as reflected in the rate of
      decline of total cellular glutathione after inhibition of its synthesis by
      buthionine sulfoximine. The extent of reversible oxidation-dependent inactivation
      of GAPDH in situ was determined by comparing the enzyme activity before and after
      reduction of cell extracts with DTT. The oxidized fraction was 0.13+/-0.02 of
      total GAPDH in control cultures and increased by 56+/-5.3% after treatment with
      1,25(OH)2D3, which did not affect the total reduced enzyme activity. Treatment
      with 1,25(OH)2D3 resulted in a approximately 40% increase in glucose-6-phosphate
      dehydrogenase, the rate-limiting enzyme in the generation of NADPH. This enzyme
      is induced in response to various modes of oxidative challenge in mammalian
      cells. Taken together, these findings indicate that 1,25(OH)2D3 causes an
      increase in the overall cellular redox potential that could translate into
      modulation of redox-sensitive enzymes and transcription factors that regulate
      cell cycle progression, differentiation, and apoptosis.

PMID- 11245449
TI  - Sensitivity to DNA damage induced by benzo(a)pyrene diol epoxide and risk of lung
      cancer: a case-control analysis.
AB  - Levels of DNA adducts vary greatly in vivo, attributable to individual
      differences in enzymatic bioactivation of benzo(a)pyrene. We developed an assay
      to measure the levels of DNA adducts induced in vitro by benzo(a)pyrene diol
      epoxide (BPDE), a bioactivated form of benzo(a)pyrene. In this large molecular
      epidemiological study of lung cancer, we tested the hypothesis that the level of
      in vitro BPDE-induced adducts is associated with risk of lung cancer. This
      hospital-based case-control study included 221 newly diagnosed lung cancer cases
      and 229 healthy controls frequency matched on age, sex, ethnicity, and smoking
      status. Short-term cultured peripheral blood lymphocytes from each subject were
      exposed in vitro to BPDE (4 microm) for 5 h, and the 32P-postlabeling method was
      then used to measure BPDE-induced DNA adducts in the host cells. Overall, the
      patients had significantly higher levels of BPDE-DNA adducts than did the
      controls (mean +/- SD per 107 nucleotides, 93.2+/-89.3 for cases versus 63.7+/
      61.1 for controls; P = 0.001). Univariate and multivariate logistic regression
      analyses were performed to calculate the crude and adjusted odds ratios and their
      95% confidence intervals. When the median adduct level of controls (46/10(7)
      nucleotides) was used as the cutoff point, 64% of cases had higher levels (odds
      ratio, 2.15; 95% confidence interval, 1.39-3.33, adjusted for age, sex,
      ethnicity, body mass index, recent weight loss, pack-years smoked, smoking in the
      last 24 h, and family history of cancer). Stratified analyses showed consistently
      higher levels of BPDE-induced adducts in cases than in controls, regardless of
      subgroup of age, sex, ethnicity, body mass index, recent weight loss, pack-years
      smoked, smoking in the last 24 h, and family history of cancer. A significant
      dose-response relationship between the quartile levels of BPDE-induced DNA
      adducts and the risk of lung cancer was observed (trend test, P < 0.001). The
      significant association between the level of in vitro BPDE-induced DNA adducts
      and risk for lung cancer suggests that subjects very sensitive to BPDE-induced
      DNA damage may have a suboptimal ability to remove the BPDE-DNA adducts and so
      are susceptible to tobacco carcinogen exposure and, therefore, may be at
      increased risk of lung cancer.

PMID- 11245450
TI  - Increased expression of cyclooxygenase-2 protein in 4-nitroquinoline-1-oxide
      induced rat tongue carcinomas and chemopreventive efficacy of a specific
      inhibitor, nimesulide.
AB  - Expression of cyclooxygenase (COX)-2 protein in 4-nitroquinoline-1-oxide (4-NQO)
      induced rat tongue lesions and the postinitiation chemopreventive potential of a
      selective COX-2 inhibitor, nimesulide (NIM), were examined in Fischer 344 male
      rats. NIM was administered in the diet at doses of 150, 300, and 600 ppm for 14
      weeks after treatment with 25-35 ppm 4-NQO in the drinking water for 12 weeks.
      Western blot analysis revealed COX-2 protein to be barely expressed in the normal
      tongue epithelia, whereas it was increased approximately 6-fold in squamous cell
      carcinomas (SCCs). Immunohistochemically, COX-2 protein was diffusely present in
      SCCs and dysplasia but expressed only in basal cells in hyperplasia and
      papillomas. In basal cells of normal epithelia, it was also occasionally weakly
      stained. NIM dose-dependently decreased at doses of 150 and 300 ppm, the
      incidences of SCCs to 4 of 12 (33.3%) and 1 of 13 (7.7%) and their multiplicity
      to 0.33+/-0.49 and 0.08+/-0.28 per rat, respectively, as compared with 4-NQO
      alone group values of 9 of 11 (81.8%) and 1.00+/-0.77. A lesser decrease was
      observed with 600 ppm, the values being 5 of 12 (41.7%) and 0.50+/-0.67. NIM did
      not significantly affect the development of hyperplasias, dysplasias, and
      papillomas. These results clearly indicate chemopreventive potential of a
      selective COX-2 inhibitor against the postinitiation development of SCCs in rat
      tongue carcinogenesis.

PMID- 11245451
TI  - Randomized trial of supplemental beta-carotene to prevent second head and neck
      cancer.
AB  - Beta-carotene has established efficacy in animal models of oral carcinogenesis
      and has been shown to regress oral precancerous lesions in humans. The purpose of
      this study was to see whether these effects extended to the prevention of
      oral/pharyngeal/laryngeal (head and neck) cancer in humans. The subject
      population for this randomized, placebo-controlled, double-blinded clinical trial
      included 264 patients who had been curatively treated for a recent early-stage
      squamous cell carcinoma of the oral cavity, pharynx, or larynx. Patients were
      assigned randomly to receive 50 mg of beta-carotene per day or placebo and were
      followed for up to 90 months for the development of second primary tumors and
      local recurrences. After a median follow-up of 51 months, there was no difference
      between the two groups in the time to failure [second primary tumors plus local
      recurrences: relative risk (RR), 0.90; 95% confidence interval (CI), 0.56-1.45].
      In site-specific analyses, supplemental beta-carotene had no significant effect
      on second head and neck cancer (RR, 0.69; 95% CI, 0.39-1.25) or lung cancer (RR,
      1.44; 95% CI, 0.62-3.39). Total mortality was not significantly affected by this
      intervention (RR, 0.86; 95% CI, 0.52-1.42). Whereas none of the effects were
      statistically significant, the point estimates suggested a possible decrease in
      second head and neck cancer risk but a possible increase in lung cancer risk.
      These effects are consistent with the effects observed in trials using
      intermediate end point biological markers in humans, in which beta-carotene has
      established efficacy in oral precancerous lesions but has no effect or slightly
      worsens sputum cytology, and in animal carcinogenicity studies, in which beta
      carotene has established efficacy in buccal pouch carcinogenesis in hamsters but
      not in animal models of respiratory tract/lung carcinogenesis, with some
      suggestions of tumor-promoting effects in respiratory tract/lung. If our results
      are replicated by other ongoing/completed trials, this suggests a critical need
      for mechanistic studies addressing differential responses in one epithelial site
      (head and neck) versus another (lung).

PMID- 11245452
TI  - Tyrosine kinase inhibition of multiple angiogenic growth factor receptors
      improves survival in mice bearing colon cancer liver metastases by inhibition of
      endothelial cell survival mechanisms.
AB  - Redundant mechanisms mediate colon cancer angiogenesis. Targeting multiple
      angiogenic factors simultaneously may improve survival of mice with colon cancer
      metastases. BALB/c mice underwent splenic injection with CT-26 colon cancer cells
      to generate liver metastases and received administration of either vehicle alone
      or a tyrosine kinase inhibitor for vascular endothelial growth factor, basic
      fibroblast growth factor, and platelet-derived growth factor receptors (SU6668).
      Mice were sacrificed when they became moribund as determined by a blinded
      observer. In a parallel experiment, groups of mice were sacrificed at earlier
      time points to better define the kinetics of the effect of SU6668 on angiogenic
      parameters over time. SU6668 increased median survival by 58% (P < 0.001) and led
      to a progressive increase in tumor cell and endothelial cell apoptosis that
      increased over time. In addition, pericyte vessel coverage and tumor vascularity
      were significantly decreased in mice treated with SU6668. Based on current
      knowledge of endothelial cell survival, these data suggest that SU6668 may
      prevent tumor endothelial cell survival directly (vascular endothelial growth
      factor) and indirectly (pericyte coverage) by affecting endothelial cell survival
      mechanisms.

PMID- 11245453
TI  - The pharmacological phenotype of combined multidrug-resistance mdr1a/1b- and mrp1
      deficient mice.
AB  - Two major classes of plasma membrane proteins that actively extrude a wide range
      of structurally diverse hydrophobic amphipathic antineoplastic agents from cells,
      with different mechanisms of action, lead to multidrug resistance. To study the
      importance of these ATP-binding cassette transporters to the toxicity of cancer
      chemotherapy agents, we have used mice genetically deficient in both the mdr1a
      and mdr1b genes [mdr1a/1b(-/-) mice], the mrp1 gene [mrp1(-/-) mice], and the
      combined genes mdr1a/1b and mrp1 [mdr1a/1b(-/-), mrp1(-/-) mice] and embryonic
      fibroblasts derived from wild-type mice and from the three gene knockout animals.
      The consequences of export pump deficiencies were evaluated primarily using
      vincristine and etoposide. Mice deficient in the three genes, mdr1a/1b and mrp1,
      exhibited a 128-fold increase in toxicity to vincristine and a 3-5-fold increase
      in toxicity to etoposide; increased toxicity to embryonic fibroblast cells from
      triple knockout mice also occurred with vincristine and etoposide. Vincristine,
      which normally does not express toxicity to the bone marrow and to the
      gastrointestinal mucosa when used at therapeutic doses, caused extensive damage
      to these tissues in mdr1a/1b(-/-), mrp1(-/-) mice. The findings indicate that the
      P-glycoprotein and mrpl are compensatory transporters for vincristine and
      etoposide in the bone marrow and the gastrointestinal mucosa and emphasize the
      potential for increased toxicities by the combined inhibition of these efflux
      pumps.

PMID- 11245454
TI  - Combination of phenylbutyrate and 13-cis retinoic acid inhibits prostate tumor
      growth and angiogenesis.
AB  - Differentiation-inducing agents, such as retinoids and short-chain fatty acids,
      have an inhibitory effect on tumor cell proliferation and tumor growth in
      preclinical studies. Clinical trials involving these compounds as single agents
      have been suboptimal in terms of clinical benefit. Our study evaluated the
      combination of phenylbutyrate (PB) and 13-cis retinoic acid (CRA) as a
      differentiation and antiangiogenesis strategy for prostate cancer. On the basis
      of previous evidence, common signal transduction pathways and possible modulation
      of retinoid receptors and retinoid response elements by PB could be responsible
      for such activities. We assessed the effect of the combination of PB and CRA on
      human and rodent prostate carcinoma cell lines. The combination of PB and CRA
      inhibited cell proliferation and increased apoptosis in vitro in an additive
      fashion as compared with single agents (P < 0.014). Prostate tumor cells treated
      with both PB and CRA revealed an increased expression of a subtype of retinoic
      acid receptor (retinoic acid receptor-beta), suggesting a molecular mechanism for
      the biological additive effect. The combination of PB and CRA also inhibited
      prostate tumor growth in vivo (up to 82-92%) as compared with single agents (P <
      0.025). Histological examination of tumor xenografts revealed decreased in vivo
      tumor cell proliferation, an increased apoptosis rate, and a reduced microvessel
      density in the animals treated with combined drugs, suggesting an
      antiangiogenesis effect of this combination. Thus, endothelial cell treatment
      with both PB and CRA resulted in reduced in vitro cell proliferation. In vivo
      testing using the Matrigel angiogenesis assay showed an additive inhibitory
      effect in the animals treated with a combination of PB + CRA (P < 0.004 versus
      single agents). In summary, this study showed an additive inhibitory effect of
      combination of differentiation agents PB and CRA on prostate tumor growth through
      a direct effect on both tumor and endothelial cells.

PMID- 11245456
TI  - Pharmacological inhibition of fatty acid synthase activity produces both
      cytostatic and cytotoxic effects modulated by p53.
AB  - Fatty acid synthetic metabolism is abnormally elevated in tumor cells, and
      pharmacological inhibitors of the anabolic enzyme fatty acid synthase (FAS),
      including the natural product cerulenin and the novel synthetic compound c75, are
      selective inhibitors of tumor cell growth. We have recently reported that these
      two FAS inhibitors both produce rapid, potent inhibition of DNA replication and S
      phase progression in human cancer cells, as well as apoptotic death. Here we
      report an additional characterization of the cellular response to FAS inhibition.
      RKO colon carcinoma cells were selected for study because they undergo little
      apoptosis within the first 24 h after FAS inhibition. Instead, RKO cells
      exhibited a biphasic stress response with a transient accumulation in S and G2 at
      4 and 8 h that corresponds to a marked reduction in cyclin A- and B1-associated
      kinase activities, and then by accumulation of p53 and p21 proteins at 16 and 24
      h and growth arrest in G1 and G2. The response of RKO cells to FAS inhibition
      resembled a genotoxic stress response, but DNA damage did not appear to be an
      important downstream effect of FAS inhibition, because none was detected using
      the single cell gel electrophoresis assay (comet assay) to assess DNA damage. p53
      function is probably important in protecting RKO cells from FAS inhibition
      because, similar to many other tumor lines, RKO cells expressing a dominant
      negative mutant p53 gene underwent extensive apoptosis within 24 h after FAS
      inhibition. Sensitization of cells to FAS inhibitors by the loss of p53 raises
      the possibility that these agents may be clinically useful against malignancies
      carrying p53 mutations. Whereas induction of apoptosis appeared related to
      accumulation of the substrate, malonyl-CoA, after FAS inhibition, the cytostatic
      effects were independent of malonyl-CoA accumulation and may have resulted from
      product depletion.

PMID- 11245455
TI  - Identification and characterization of A-105972, an antineoplastic agent.
AB  - A high-throughput screening assay was designed to select compounds that inhibit
      the growth of cultured mammalian cells. After screening more than 60,000
      compounds, A-105972 was identified and selected for further testing. A-105972 is
      a small molecule that inhibits the growth of breast, central nervous system,
      colon, liver, lung, and prostate cancer cell lines, including multidrug-resistant
      cells. The cytotoxic IC50 values of A-105972 were between 20 and 200 nM,
      depending on the specific cell type. The potency of A-105972 is similar in cells
      expressing wild-type or mutant p53. A majority of cells treated with A-105972
      were trapped in the G2-M phases, suggesting that A-105972 inhibits the
      progression of the cell cycle. Using [3H]A-105972, we found that A-105972 bound
      to purified tubulin. Unlabeled A-105972 competed with [3H]A-105972 binding with
      an IC50 value of 3.6 microL. Colchicine partially inhibited [3H]A-105972 binding
      with an IC50 value of approximately 90 microM, whereas paclitaxel and vinblastine
      had no significant effect. Tumor cells treated with A-105972 were observed to
      contain abnormal microtubule arrangement and apoptotic bodies. DNA ladder studies
      also indicated that A-105972 induced apoptosis. A-105972 caused a mobility shift
      of bcl-2 on SDS-PAGE, suggesting that A-105972 induced bcl-2 phosphorylation. A
      105972 treatment increased the life span of mice inoculated with B16 melanoma,
      P388 leukemia, and Adriamycin-resistant P388. These results suggest that A-105972
      is a small molecule that interacts with microtubules, arrests cells in G2-M
      phases, and induces apoptosis in both multidrug resistance-negative and multidrug
      resistance-positive cancer cells. A-105972 and its analogues may be useful for
      treating cell proliferative disorders such as cancer.

PMID- 11245457
TI  - The level of MHC class I expression on murine adenocarcinoma can change the
      antitumor effector mechanism of immunocytokine therapy.
AB  - The huKS1/4-IL2 fusion protein, directed against the human epithelial cell
      adhesion molecule (huEpCAM) has been shown to induce a strong CD8+ T-cell
      dependent, natural killer (NK) cell-independent, antitumor response in mice
      bearing the huEp-CAM-transfected CT26 colon cancer CT26-EpCAM. Here we
      investigate the effectiveness of huKS1/4-IL2 against CT26-Ep21.6, a subclone of
      CT26-EpCAM, expressing low levels of MHC class I. In vitro antibody-dependent
      cellular cytotoxicity (ADCC) assays in the presence of huKS1/4-IL2 demonstrate
      that murine NK cells from spleen and blood can kill CT26-Ep21.6 significantly
      better than they kill CT26-EpCAM. NK-mediated ADCC of CT26-EpCAM can be enhanced
      by blocking the murine NK cell-inhibitory receptor, Ly-49C. A potent in vivo
      antitumor effect was observed when BALB/c mice bearing experimental metastases of
      CT26-Ep21.6 were treated with huKS1/4-IL2. The depletion of NK cells during
      huKS1/4-IL2 treatment significantly reduced the antitumor effect against CT26
      Ep21.6. Together our in vitro and in vivo data in the huEp-CAM-transfected CT26
      models indicate that the amount of MHC class I expressed on the tumor target cell
      plays a critical role in the in vivo antitumor mechanism of huKS1/4-IL2
      immunotherapy. A low MHC class I level favors NK cells as effectors, whereas a
      high level of MHC class I favors T cells as effectors. Given the heterogeneity of
      MHC class I expression seen in human tumors and the prevailing T-cell suppression
      in many cancer patients, the observation that huKS1/4-IL2 has the potential to
      effectively activate an NK cell-based antitumor response may be of potential
      clinical relevance.

PMID- 11245458
TI  - P53 modulates the effect of loss of DNA mismatch repair on the sensitivity of
      human colon cancer cells to the cytotoxic and mutagenic effects of cisplatin.
AB  - This study examined how the DNA mismatch repair (MMR) system and p53 interact to
      maintain genomic integrity in the presence of the mutagenic stress induced by
      cisplatin (DDP). Sensitivity to the cytotoxic and mutagenic effect of DDP was
      assessed using a panel of sublines of the MMR-deficient HCT116 colon carcinoma
      cells in which MMR function had been restored by transfer of a copy of MLH1 on
      chromosome 3 or in which p53 function had been disabled by expression of HPV-16
      E6. Loss of p53 function by expression of E6 in MMR-proficient HCT116+ ch3 cells
      conferred only 1.1-2.0-fold resistance to a panel of commonly used
      chemotherapeutic agents, whereas disruption of p53 in MMR-deficient HCT116 cells
      resulted in substantial levels of resistance to some agents (paclitaxel, 1.9
      fold; gemcitabine, 2.7-fold; 6-thioguanine, 3.3-fold; and etoposide, 4.4-fold)
      but sensitization to other agents (topotecan, 2.5-fold; and DDP, 3.3-fold). Loss
      of MMR or p53 alone had only a minor effect on sensitivity to the mutagenic
      effect of DDP as measured by the appearance of variants resistant to 6
      thioguanine, etoposide, topotecan, gemcitabine, and paclitaxel in the population
      10 days later (1.0-2.4-fold), whereas loss of both p53 and MMR had a more
      profound effect (1.7-6.5-fold). Loss of both p53 and MMR increased the basal
      frequency insertion/deletion mutations detected by a shuttle vector-based assay
      to a greater extent than loss of either alone. In association with DDP-induced
      injury, loss of p53 or MMR alone resulted in 1.2- and 1.7-fold more mutations,
      whereas loss of both resulted in a 5.1-fold increase in mutant frequency.
      Examination of the impact of loss of p53 and/or MMR on the DDP-induced cell cycle
      checkpoint activation, p53 induction, ability of the cell to tolerate adducts in
      its DNA, and the rate of disappearance of platinum from genomic DNA indicated the
      effects of the loss of p53 and/or MMR on all of these parameters, suggesting a
      multifactorial etiology for the changes in sensitivity to the cytotoxic and
      mutagenic effects of DDP. These results indicate that p53 and MMR can cooperate
      to control sensitivity to the cytotoxic effect of DDP and to limit its mutagenic
      potential in the colon cancer cells.

PMID- 11245459
TI  - Interferon-inducible protein 10 induction and inhibition of angiogenesis in vivo
      by the antitumor agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA).
AB  - 5,6-Dimethylxanthenone-4-acetic acid (DMXAA), a drug synthesized in this
      laboratory that halts tumor blood flow and induces tumor hemorrhagic necrosis in
      transplantable murine tumors, is known to induce the synthesis of antiangiogenic
      cytokines in vitro. We have measured the induction of mRNA for modulators of
      angiogenesis in vivo and investigated whether DMXAA may also have an additional
      antiangiogenic action through the production of these cytokines. The genes for
      IFN-alpha and for interferon-inducible protein 10 (IP-10) were strongly induced
      in both spleen and Colon 38 tumor tissue after DMXAA treatment, whereas that for
      IFN-gamma was induced in spleen but not in tumor. Expression of mRNA for IFN-beta
      and for the p35 or the p40 subunits of interleukin 12 was not observed in either
      tissue. Splenic IP-10 mRNA induction was not a result of IFN-gamma production
      induced with DMXAA because spleen tissue from DMXAA-treated mice that lacked
      functional IFN-gamma receptors expressed similar amounts of IP-10 mRNA as those
      from wild-type mice. A single i.p. injection of DMXAA (20 mg/kg) was sufficient
      to reduce fibroblast growth factor-induced endothelial cell invasion of Matrigel
      implants in athymic nude mice by nearly 100%. The inactive analogue 8
      methylxanthenone-4-acetic acid did not up-regulate the genes for IP-10 or IFNs
      and did not inhibit endothelial cell invasion. Antibodies to IP-10 reversed the
      inhibition of DMXAA of endothelial cell invasion by 58%; antibodies to tumor
      necrosis factor-alpha, IFN-gamma, and IFN-alpha reversed inhibition by 7%, 5%,
      and 0%, respectively. The data support the hypothesis that DMXAA, in addition to
      antivascular effects mediated by tumor necrosis factor-alpha, may have an
      antiangiogenic effect mediated largely by the induction of IP-10.

PMID- 11245460
TI  - Methotrexate accumulates to similar levels in animals transplanted with normal
      versus drug-resistant transgenic marrow.
AB  - Gene transfer and expression of methotrexate (MTX)-resistant variants of
      dihydrofolate reductase (DHFR) in normal hematopoietic cells is a potential
      strategy to permit administration of larger doses of MTX by alleviating drug
      toxicity in normal cells and tissues that are drug sensitive. We have previously
      demonstrated that transplantation of marrow from transgenic mice expressing drug
      resistant DHFRs conferred upon normal recipient animals resistance to MTX at
      levels that are usually toxic for hematopoietic and gastrointestinal (GI)
      tissues. One explanation for the observed protection from GI toxicity by drug
      resistant marrow is that MTX could be cleared more rapidly in animals maintaining
      a more healthy hematopoietic system. To evaluate this possibility, we carried out
      MTX pharmacokinetic studies in mice that received transplanted transgenic marrow
      expressing either of two different DHFR variants, administering increasing doses
      of MTX up to 4 mg/kg/day. Animals received i.p. injection precisely every 24 h.
      Every 4 days, three animals from each group were sacrificed, and their plasma and
      intestines were assayed for MTX. Animals transplanted with transgenic Arg-22 DHFR
      drug-resistant marrow maintained hematocrit levels that were about 4-fold higher
      at 3 weeks after transplant than those of untreated animals or animals that
      received normal marrow cells. Animals that received normal marrow did not survive
      beyond 25 days and did not accumulate higher levels of MTX than animals that
      received a transgenic marrow transplant. Untreated animals exhibited a higher
      rate of survival (36 days) but again did not accumulate higher levels of MTX than
      the transgenic marrow recipients. When the experiment was repeated using
      transgenic Tyr-22 DHFR marrow, the levels of MTX in the plasma or GI tissues did
      not differ significantly between groups. Intestinal concentrations of MTX in both
      experiments were about 4-5-fold higher than those in the plasma. These results
      indicate that protection from MTX toxicity conferred by expression of drug
      resistant DHFR activity in the marrow is not the result of a higher rate of MTX
      clearance from the circulation in comparison with control animals but a true
      resistance of hematopoietic and GI tissues to MTX. The maintenance of antifolate
      levels in animals protected from MTX toxicity implies that this procedure should
      not compromise the antitumor efficacy of MTX.

PMID- 11245461
TI  - Antitumor activity of the rapamycin analog CCI-779 in human primitive
      neuroectodermal tumor/medulloblastoma models as single agent and in combination
      chemotherapy.
AB  - We examined the cytotoxicity of the immunosuppressant agent rapamycin and its
      analogue CCI-779 in human brain tumor cell lines in vitro and in vivo as single
      agents and in combination with standard chemotherapeutic drugs. In the rapamycin
      sensitive PNET/MB cell line DAOY, rapamycin exhibited additive cytotoxicity with
      cisplatin and with camptothecin. In vivo, CCI-779 delayed DAOY xenograft growth
      by 160% after 1 week and 240% after 2 weeks of systemic treatment, compared with
      controls. Single high-dose treatment induced 37% regression of tumor solume.
      Growth inhibition of DAOY xenografts was 1.3 times greater after simultaneous
      treatment with CCI-779 and cisplatin than after cisplatin alone. Interestingly,
      CCI-779 also produced growth inhibition of xenografts derived from U251 malignant
      glioma cells, a human cell line resistant to rapamycin in vitro. These studies
      suggest that the rapamycin analogue CCI-779 is an important new agent to
      investigate in the treatment of human brain tumors, particularly PNET/MB.

PMID- 11245462
TI  - Inhibition of extracellular signal-regulated kinase (ERK) mediates cell cycle
      phase independent apoptosis in vinblastine-treated ML-1 cells.
AB  - Chemotherapeutic agents induce alterations in intracellular signal transduction
      cascades that culminate in the initiation of the apoptotic program. Here, the
      relationship between the mitogen-activated protein kinase (MAPK) response and
      apoptosis in ML-1 cells treated with vinblastine and paclitaxel was investigated.
      We show that these compounds elicit different effects on MAPKs with vinblastine,
      but not paclitaxel, increasing both c-Jun-NH2-terminal kinase (JNK) and p38
      activity. However, vinblastine and paclitaxel both induced apoptosis with similar
      kinetics, suggesting that increased JNK and p38 activity is not required for
      apoptosis that is induced by microtubule interfering agents. Strikingly, the
      abrogation of extracellular signal-regulated kinase (ERK)-signaling by the
      MAPK/ERK kinase (MEK)1/2 inhibitor PD098059 in combination with vinblastine
      robustly induced apoptosis in ML-1 cells at a rate much faster than treatment
      with vinblastine alone and occurred at all phases of the cell cycle. This
      apoptotic induction was attributed to JNK activation because: (a) non-JNK
      activating concentrations of vinblastine failed to increase apoptosis in the
      presence of PD098059; (b) apoptosis induced by paclitaxel, which did not activate
      JNK, was not potentiated by PD098059; and (c) transduction of an inhibitor of JNK
      activity partially suppressed both JNK activity and apoptosis induced by
      vinblastine plus PD098059. Additionally, we found that the activation of JNK by
      vinblastine occurred upstream of effector caspase activation because treatment
      with a pan-specific caspase inhibitor (valine-alanine-aspartate
      fluoromethylketone) resulted in complete abrogation of apoptosis with no effect
      on MAPK signaling. Taken together, these data suggest that inhibition of the MEK-
      >ERK signal transduction cascade alleviates cell cycle dependence for vinblastine
      induced apoptosis by a mechanism that requires JNK activation.

PMID- 11245463
TI  - Inhibition of extracellular signal-regulated kinase 1/2 phosphorylation and
      induction of apoptosis by sulindac metabolites.
AB  - Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and
      sulindac is associated with a decreased mortality from colorectal cancer.
      Sulindac causes regression of precancerous adenomatous polyps and inhibits the
      growth of cultured colon cell lines. Whereas induction of apoptotic cell death is
      thought to account for the growth inhibitory effect of sulindac, less is known
      about its biochemical mechanism(s) of action. Sulindac is metabolized in vivo to
      sulfide and sulfone derivatives. Both the sulfide and sulfone metabolites of
      sulindac as well as more potent cyclic GMP-dependent phosphodiesterase inhibitors
      were shown to cause inhibition of extracellular signal-regulated kinase (ERK)1/2
      phosphorylation at doses (40-600 microM) and times (1-5 days) consistent with the
      induction of apoptosis by the drugs. Treatment of HCT116 human colon cancer cells
      with the specific mitogen-activated protein kinase kinase, U0126 (5-50 microM)
      resulted in a time- and dose-dependent inhibition of ERK1/2 phosphorylation, and
      induction of apoptosis. U0126 treatment (20 microM) increased basal apoptosis,
      and potentiated the apoptotic effect of sulindac sulfide and sulindac sulfone.
      These results suggest that the inhibition of ERK1/2 phosphorylation is
      responsible for at least part of the induction of programmed cell death by
      sulindac metabolites. Inhibition of ERK1/2 activity may, therefore, be a useful
      biochemical target for the development of chemopreventive and chemotherapeutic
      drugs for human colon cancer.

PMID- 11245464
TI  - Targeting a genetically engineered elastin-like polypeptide to solid tumors by
      local hyperthermia.
AB  - Elastin-like polypeptides (ELPs) are biopolymers of the pentapeptide repeat Val
      Pro-Gly-Xaa-Gly that undergo an inverse temperature phase transition. They are
      soluble in aqueous solutions below their transition temperature (T1) but
      hydrophobically collapse and aggregate at temperatures greater than T1. We
      hypothesized that ELPs conjugated to drugs would enable thermally targeted drug
      delivery to solid tumors if their T1 were between body temperature and the
      temperature in a locally heated region. To test this hypothesis, we synthesized a
      thermally responsive ELP with a T1 of 41 degrees C and a thermally unresponsive
      control ELP in Escherichia coli using recombinant DNA techniques. In vivo
      fluorescence videomicroscopy and radiolabel distribution studies of ELP delivery
      to human tumors (SKOV-3 ovarian carcinoma and D-54MG glioma) implanted in nude
      mice demonstrated that hyperthermic targeting of the thermally responsive ELP for
      1 h provides a approximately 2-fold increase in tumor localization compared to
      the same polypeptide without hyperthermia. We observed aggregates of the
      thermally responsive ELP by fluorescence videomicroscopy within the heated tumor
      microvasculature but not in control experiments, which demonstrates that the
      phase transition of the thermally responsive ELP carrier can be engineered to
      occur in vivo at a specified temperature. By exploiting the phase transition
      induced aggregation of these polypeptides, this method provides a new way to
      thermally target polymer-drug conjugates to solid tumors.

PMID- 11245465
TI  - Antibodies elicited by naked DNA vaccination against the complementary
      determining region 3 hypervariable region of immunoglobulin heavy chain idiotypic
      determinants of B-lymphoproliferative disorders specifically react with patients'
      tumor cells.
AB  - Several reports have suggested that the mechanism of protection induced by
      antiidiotypic vaccination against low-grade lymphoproliferative disorders is
      likely to be antibody mediated. Here we test the hypothesis that DNA vaccination
      with the short peptide encompassing the complementary-determining region 3
      hypervariable region of immunoglobulin heavy chain (VH-CDR3) may elicit a
      specific antibody immune response able to recognize the native antigens in the
      form required for therapy. As a test system, we used the VH-CDR3 sequences
      derived from two patients with non-Hodgkin's B lymphomas (PA, AS) and one patient
      with hairy cell leukemia (BA) to immunize outbred Swiss mice. This experimental
      model could mimic a clinical setting in which different patients present distinct
      HLA haplotypes. Individual tumor-specific VH-CDR3 sequences were amplified by a
      two-step procedure and directly cloned into multigenic plasmid vectors (pRC100
      and derived) with and without mouse interleukin 2 (mIL-2). Each tumor-specific
      sequence was characterized by sequencing. Female Swiss mice were vaccinated i.m.
      with plasmids expressing the tumor-specific VH-CDR3 sequence alone (pRC101-PA),
      mIL-2 plus the VH-CDR3 sequence (pRC111-PA), or a different unrelated antigen
      (NS3 of hepatitis C virus; pRC112), the sole mIL-2 (pRC110), and the empty
      plasmid (pRC100). Boost injections were performed at 3 and 16 weeks from the
      first vaccination, and sera were drawn before each vaccination and at 6, 9, and
      19 weeks. Induction of anti-VH-CDR3s antibodies in the sera and their ability to
      recognize native antigens on patients' tumor cells were evaluated by FACS
      analysis. Up to 56% (n = 25) of mice vaccinated with pRC111-PA plasmid and 20% (n
      = 15) of mice vaccinated with pRC101-PA developed a specific immune response that
      was maintained throughout 19 weeks of observation in 40% of pRC111-PA-vaccinated
      mice. No response was detected in sera obtained from mice vaccinated with the
      other plasmids (n = 45). pRC111-PA injection s.c. was less effective (13%, n =
      15) than i.m. injection (53%, n = 15). Indeed, we demonstrated that antibodies
      elicited by naked DNA vaccination against three different patient-derived VH-CDR3
      peptides (pRC111-PA or BA or AS) readily reacted with binding epitopes on the
      idiotypic proteins expressed on the surface of tumor cells derived from each
      patient; 60, 40, and 40% of, respectively, PA-, BA-, and AS-vaccinated mice
      developed specific antibodies. No cross-reactivity was detected among the three
      different CDR3s against tumor cells derived from the other two patients. The
      outbred mouse strategy confirmed the significant matching potential of three
      different VH-CDR3 peptides to be efficaciously presented through different MHCs.
      We conclude that individual VH-CDR3 DNA vaccination can result in a potentially
      effective specific immune response against non-Hodgkin's B lymphoma cells by a
      rapid and low-cost therapeutic approach.

PMID- 11245466
TI  - Identification and characterization of prostein, a novel prostate-specific
      protein.
AB  - In this report, we describe the application of a systematic, genome-based
      approach to identify prostein, a novel prostate-specific protein expressed in
      normal and malignant prostate tissues. Characterization of the prostein gene
      shows that prostein cDNA encodes a 553-amino acid protein. The protein is
      predicted to be a type IIIa plasma membrane protein with a cleavable signal
      peptide and 11 transmembrane-spanning regions. The prostein gene is located on
      chromosome 1 at the WI-9641 locus between q32 and q42. Prostein mRNA is shown to
      be uniquely expressed in normal and cancerous prostate tissues using Northern
      blot, eDNA microarray, and real-time PCR analyses. Furthermore, prostein mRNA
      expression does not appear to be prostate tumor grade related and is restricted
      exclusively to prostate cell lines. Immunohistochemical staining using a mouse
      monoclonal antibody generated against prostein demonstrates that this protein is
      specifically detected in prostate tissues both at the plasma membrane and in the
      cytoplasm. Prostein expression is androgen responsive because treatment of LNCaP
      cells with androgen up-regulates prostein message and protein expression levels.
      These results validate prostein as a prostate-specific marker with potential
      utility in the diagnosis and treatment of prostate cancer.

PMID- 11245467
TI  - Gene expression patterns associated with the metastatic phenotype in rodent and
      human tumors.
AB  - Using subtractive technology, we have generated metastasis-associated gene
      expression profiles for rat mammary and pancreatic adenocarcinomas. Several genes
      whose expression is thought to be related to tumor progression such as c-Met,
      urokinase-type plasminogen activator receptor, ezrin, HMG-1, oncomodulin,
      cathepsin, and caveolin were thereby isolated. Half of the metastasis-associated
      clones showed no significant homology to genes with known function. Notably,
      several of the metastasis-associated clones were also expressed in metastatic
      lines but not in nonmetastatic lines of other tumor models. Furthermore, in situ
      hybridization using selected clones documents the relevance of these results for
      human cancer because strong expression in tumor cells including metastases was
      detected in human colorectal cancer samples and, to a lesser extent, in mammary
      cancer samples. These data support the concept that tumors express a "metastatic
      program" of genes.

PMID- 11245468
TI  - Effect of adenoviral transduction of the fragile histidine triad gene into
      esophageal cancer cells.
AB  - Reintroduction of a tumor suppressor gene product in cancer cells is a promising
      strategy for cancer gene therapy. The fragile histidine triad (FHIT) gene has
      been identified in a region at chromosome 3p14.2, which is deleted in many
      tumors, including esophageal cancer. Previous studies have shown frequent
      biallelic alterations of the FHIT gene in numerous tumors, and have demonstrated
      a tumor suppressor function of Fhit. We have studied the biological effects of
      adenoviral-FHIT transduction in esophageal cancer cell lines. Results showed
      suppression of cell growth in vitro in three of seven esophageal cancer cell
      lines, all seven of which showed abundant expression of the transgene. Adenoviral
      FHIT expression, but not control adenoviral infections, induced caspase-dependent
      apoptosis in two esophageal cancer cell lines, TE14 and TE4, which express no or
      very little Fhit, respectively. Treatment of TE14 cells with adenoviral-FHIT
      vectors resulted in abrogation of tumorigenicity in nude mice. A third esophageal
      cancer cell line, TE12, without detectable endogenous Fhit, showed accumulation
      of cells at S to G2-M and a small apoptotic cell fraction after adenoviral-FHIT
      transduction. Thus, adenoviral-FHIT expression can inhibit the growth of
      esophageal cancer cells, at least in part through caspase-dependent apoptosis,
      suggesting that adenoviral-FHIT infection should be explored as a therapeutic
      strategy.

PMID- 11245469
TI  - End-joining deficiency and radiosensitization induced by gemcitabine.
AB  - The mechanism of radiosensitization by gemcitabine (2',2'-difluoro-2'
      deoxycytidine, dFdC) is not exactly known. We investigated the possible role of
      inhibition of the repair of DNA double-strand breaks by dFdC by measuring the
      extent of radiosensitization in different cell lines deficient and proficient in
      components of nonhomologous end-joining and in the parental cell lines. Different
      cell lines were incubated with 0.5 and 5 microM dFdC for 4 h. Cells deficient in
      DNA-dependent protein-kinase catalytic subunit (V3) showed sensitization similar
      to that of wild-type cells (AAS) and complemented cells (V3+YAC). Ku80-deficient
      cells (xrs5 and xrs6) showed even more radiosensitization by dFdC as compared
      with wild-type CHO-K1. However, Ku80-complemented cell lines (xrs5+huKu80 and
      xrs6+haKu80) did not show radiosensitization. The differences in dFdC-mediated
      radiosensitization were not attributable to different changes in deoxynucleotide
      triphosphate levels and cell cycle distribution. We conclude that a functional
      nonhomologous end-joining pathway is not required for dFdC-mediated
      radiosensitization.

PMID- 11245470
TI  - Transcriptional activation of the human HMG1 gene in cisplatin-resistant human
      cancer cells.
AB  - The nonhistone chromosomal protein, high mobility group 1 (HMG1), which is
      ubiquitously expressed in higher eukaryotic cells, preferentially binds to
      cisplatin-modified DNA. The observation that HMG1 is overexpressed in cisplatin
      resistant human cancer cells suggests that cisplatin resistance may be closely
      associated with HMG1. To decipher the mechanism of HMG1 overexpression in
      cisplatin-resistant cells, we isolated two overlapping genomic DNA clones
      containing the entire human HMG1 gene. These clones, which span approximately 15
      kb of contiguous DNA, include 5 kb of the 5' flanking region as well as the
      entire coding sequence. We sequenced 1500 bp upstream of the first exon. The
      segment proximal to the transcription initiation site did not contain a TATA box
      but did possess an activating transcription factor site, an activator protein-2
      site, one CCAAT box, and two CCAAT-binding transcription factor/nuclear factor-1
      (CTF/NF-1) sites. HMG1 promoter activity was 3-10-fold higher in cisplatin
      resistant KB-CP20 cells than in parental KB cells. An in vivo footprint
      experiment showed several differences of dimethyl sulfate modifications between
      KB and KB-CP20 cells in the area around the CTF/NF-1 sites. In addition,
      electrophoretic gel mobility shift assays showed that binding of a nuclear factor
      from cisplatin-resistant cells to the CTF/NF-1 site was significantly higher than
      the binding of the same factor from parental cells. Semiquantitative reverse
      transcription-PCR and Western blot analysis also showed that expression of CTF/NF
      1 was 3-20-fold higher in the resistant cell line than in its parental
      counterpart. These findings suggest that, in cisplatin-resistant cells, the
      expression of HMG1 gene product is enhanced at the transcriptional level and that
      this probably occurs through the enhanced expression of the CCAAT binding factor,
      CTF/NF-1.

PMID- 11245471
TI  - A possible role of p73 on the modulation of p53 level through MDM2.
AB  - MDM2, one of the transcriptional targets of p53, can target p53 for degradation
      in a negative feedback loop. The p53-related protein p73, however, can bind to
      MDM2 but is not consequently down-regulated. Here we demonstrate that p73 could
      transactivate the MDM2 promoter in p53-null cell lines. In p53-null cell lines,
      the level of MDM2 was increased by p73 due to increases in transcription and
      protein stability of MDM2. In transient transfection assays, inhibition of the
      transcriptional activity of p73 required a higher amount of MDM2 than that of
      p53. This is probably due to the fact that MDM2 can target p53, but not p73, for
      degradation. We demonstrated further that the level of p53 could be altered by a
      cooperation between MDM2 and p73, but not by transcriptional inactive mutants of
      p73. Expression of p73 resulted in a reduction of the ectopically expressed p53
      in transient transfections or of the endogenous p53 induced by Adriamycin- or UV
      mediated damage. These reductions of p53 were likely to be due to an increase in
      MDM2-mediated proteolysis. These results suggest the possibility that different
      levels of p73 in the cell may act as a mechanism to modulate p53 responses after
      DNA damage and other stresses and that an increase rather than a decrease in p73
      may play a role in tumorigenesis.

PMID- 11245472
TI  - Resveratrol-induced activation of p53 and apoptosis is mediated by extracellular
      signal-regulated protein kinases and p38 kinase.
AB  - Resveratrol, a phytoalexin found in grapes, berries, and peanuts, is one of the
      most promising agents for cancer prevention. Our previous study showed that the
      antitumor activity of resveratrol occurs through p53-mediated apoptosis. In this
      study, we have elucidated the potential signaling components underlying
      resveratrol-induced p53 activation and induction of apoptosis. We found that in a
      mouse JB6 epidermal cell line, resveratrol activated extracellular-signal
      regulated protein kinases (ERKs), c-Jun NH2-terminal kinases (JNKs), and p38
      kinase and induced serine 15 phosphorylation of p53. Stable expression of a
      dominant negative mutant of ERK2 or p38 kinase or their respective inhibitor,
      PD98059 or SB202190, repressed the phosphorylation of p53 at serine 15. In
      contrast, overexpression of a dominant negative mutant of JNKI had no effect on
      the phosphorylation. Most importantly, ERKs and p38 kinase formed a complex with
      p53 after treatment with resveratrol. Strikingly, resveratrol-activated ERKs and
      p38 kinase, but not JNKs, phosphorylated p53 at serine 15 in vitro. Furthermore,
      pretreatment of the cells with PD98059 or SB202190 or stable expression of a
      dominant negative mutant of ERK2 or p38 kinase impaired resveratrol-induced p53
      dependent transcriptional activity and apoptosis, whereas constitutively active
      MEK1 increased the transcriptional activity of p53. These data strongly suggest
      that both ERKs and p38 kinase mediate resveratrol-induced activation of p53 and
      apoptosis through phosphorylation of p53 at serine 15.

PMID- 11245473
TI  - Prostate short-chain dehydrogenase reductase 1 (PSDR1): a new member of the short
      chain steroid dehydrogenase/reductase family highly expressed in normal and
      neoplastic prostate epithelium.
AB  - Genes regulated by androgenic hormones are of critical importance for the normal
      physiological function of the human prostate gland, and they contribute to the
      development and progression of prostate carcinoma. We used cDNA microarrays
      comprised of prostate-derived cDNAs to profile transcripts regulated by androgens
      in prostate cancer cells. This study identified a novel gene that we have
      designated prostate short-chain dehydrogenase/reductase 1 (PSDR1), that exhibits
      increased expression on exposure to androgens in the LNCaP prostate cancer cell
      line. Northern analysis demonstrated that PSDR1 is highly expressed in the
      prostate gland relative to other normal human tissues. The PSDR1 cDNA and
      putative protein exhibit homology to the family of short-chain
      dehydrogenase/reductase enzymes and thus identify a new member of this family.
      Cloning and analysis of the putative PSDR1 promoter region identified a potential
      androgen-response element. We used a radiation-hybrid panel to map the PSDR1 gene
      to chromosome 14q23-24.3. In situ hybridization localizes PSDR1 expression to
      normal and neoplastic prostate epithelium. These results identify a new gene
      involved in the androgen receptor-regulated gene network of the human prostate
      that may play a role in the pathogenesis of prostate carcinoma.

PMID- 11245474
TI  - MSH6 and MSH3 are rarely involved in genetic predisposition to nonpolypotic colon
      cancer.
AB  - A set of 90 nonpolypotic colon cancer families in which germ-line mutations of
      MSH2 and MLH1 had been excluded were screened for mutations in two additional DNA
      mismatch repair genes, MSH6 and MSH3. Kindreds fulfilling and not fulfilling the
      Amsterdam I criteria, showing early and late onset colorectal (and other)
      cancers, and having microsatellite stable and unstable tumors were included. Two
      partly parallel approaches were used: genetic linkage analysis (19 large
      families) and the protein truncation test (85, mostly smaller, families). Whereas
      MSH3 was not involved in any family, a large Amsterdam-positive, late-onset
      family showed a novel germ-line mutation in MSH6 (deletion of CT at nucleotide
      3052 in exon 4). The mutation was identified through genetic linkage (multipoint
      lod score 2.4) and subsequent sequencing of MSH6. Furthermore, the entire MSH6
      gene was sequenced exon by exon in families with frameshift mutations in the (C)8
      tract in tumors, previously suggested as a predictor of MSH6 germ-line mutations;
      no mutations were found. We conclude that germ-line involvement of MSH6 and MSH3
      is rare and that other genes are likely to account for a majority of MSH2-, MLH1
      mutation negative families with nonpolypotic colon cancer.

PMID- 11245475
TI  - Cancer-specific genomic instability in bronchial lavage: a molecular tool for
      lung cancer detection.
AB  - We examined genomic instability in DNA from 80 bronchial lavage samples from
      patients with lung cancer and individuals with no malignant lung disease. We used
      a multiplex assay of eight fluorescent-tagged microsatellite markers that have a
      very high incidence of allelic imbalance in lung tumors. When genomic instability
      at individual loci was analyzed statistically against diagnosis, markers D3S1289
      (P = 0.033), D3S1300 (P = 0.001), D13S171 (P = 0.009), and D17S2179E (P = 0.017)
      demonstrated significantly higher frequency of instability in bronchial lavage
      specimens from lung cancer cases than those with nonmalignant conditions. In
      contrast, markers D9S157, D9S161, D13S153, and D5S644 demonstrated lower
      specificity (P > 0.05) for lung tumors. These results suggest that genomic
      instability in some loci may be related to high proliferation rates but not
      necessarily to cell commitment to malignancy. When genomic instability was scored
      with only the four cancer-specific markers, the assay produced a sensitivity of
      73.9% and a specificity of 76.5%. On combining the results from the cytological
      examination and the molecular assay, the sensitivity reached 82.6%. These results
      indicate that in our efforts to investigate genomic instability as a potential
      marker for the early detection of lung cancer, we need to identify cancer
      specific genomic instability markers. This paper has shown that these first four
      markers may be considered to form an individual set of cancer-specific genomic
      instability markers.

PMID- 11245476
TI  - Templated nucleotide addition and immunoglobulin JH-gene utilization in t(11;14)
      junctions: implications for the mechanism of translocation and the origin of
      mantle cell lymphoma.
AB  - The t(11;14)(q13;q32) between the BCL-1 and immunoglobulin heavy chain gene (IgH)
      loci in mantle cell lymphoma (MCL) are believed to be mediated by the mechanism
      of V(D)J recombination similar to the t(14; 18) in follicular lymphoma (FL). We
      have recently shown that the t(14;18) event creates staggered double-strand
      breaks in the BCL-2 locus, and that the t(14;18) junctions contain templated
      nucleotide insertions (T-nucleotides; U. Jager et al., Blood, 95: 3520-3529,
      2000). Reasoning that the earlier (pregerminal center) B-cell origin of MCL might
      be reflected in a different molecular structure of the chromosomal breakpoints,
      we PCR-amplified diagnostic samples from 93 patients. Thirty-six samples (39%)
      were positive for the direct (BCL-1/J(H)) and 23 for both direct and reciprocal
      (D(H)/BCL-1) junctions. The breaks on chromosome 14 exhibited features of V(D)J
      mediated recombination as shown by D(H) and J(H) coding end processing. However,
      duplications of BCL-1 sequences in 39% of the 23 patients indicate staggered
      double-strand breaks in the major translocation cluster region (MTC). This is
      incompatible with V(D)J recombination and indicates a different mechanism of
      cleavage. The use of J(H)6 in the junctions (39%) was similar to that in the
      immunoglobulin genes of normal B cells and B-CLL, but considerably less than in
      FL. Only 2 of 36 samples contained a BCL-1/DJ(H) rearrangement, which was
      indicative of a previous DJ(H) rearrangement. Most importantly, 19% of the BCL
      1/IgH junctions with inserts of > or =5 nucleotides contained error-prone copies
      (T-nucleotides) of 8-12 nucleotides originating from the surrounding BCL-1 or IgH
      regions, a lower rate than in FL. No correlation was found between the addition
      of T-nucleotides and the rate of somatic mutation in the immunoglobulin genes. We
      conclude that the t(11;14) and t(14;18) use the same basic mechanism of
      translocation including V(D)J-mediated recombination, double-strand staggered
      breaks, and template-dependent, error-prone DNA-synthesis. However, the distinct
      differences in the utilization of J(H) regions suggest that the t(11;14) occurs
      predominantly during an attempted primary D(H)-J(H) rearrangement in early B
      cells, whereas the t(14;18) mostly occurs during secondary rearrangement. This is
      in agreement with the pregerminal center B-cell origin of MCL.

PMID- 11245477
TI  - Receptor activator of nuclear factor kappaB ligand (RANKL) is a key molecule of
      osteoclast formation for bone metastasis in a newly developed model of human
      neuroblastoma.
AB  - Neuroblastoma originates from neural crest cells and is the most common
      extracranial solid tumor in childhood. Bone metastasis in neuroblastoma is an
      unfavorable prognostic factor even with intensive therapy. In the present study,
      we screened four cell lines of human neuroblastoma (NB-1, NB-16, NB-19, and NH-6)
      for tumorigenicity and metastatic capacity in nude mice and found that NB-19
      cells caused osteolytic lesions after s.c. injection into mice. To detect
      micrometastases in the host tissue, we performed two kinds of PCR-based
      metastasis assays: (a) genomic PCR assay using the primers for human genome
      specific Alu sequence; and (b) reverse transcription-nested PCR assay that
      detects the expression of tyrosine hydroxylase, a marker specific for
      neuroblastoma. The results of these PCR assays revealed the colonization of human
      neuroblastoma cells in the bone marrow of the mice that had received the s.c.
      injection of NB-19 cells. Because osteoclastic bone resorption has been reported
      to play important roles in osteolysis in some cancers such as breast cancer, we
      next examined the osteoclast (OC)-inducing activity of NB-19 cells using a
      coculture system in which NB-19 cells were cultured with murine bone marrow cells
      containing OC precursors and stromal cells. NB-19 cells induced tartrate
      resistant acid phosphatase-positive multinucleated OC-like cells without
      requirement of 1,25-dihydroxyvitamin D3 or other osteoclastogenic stimulators. To
      investigate the factors involved in the osteoclastogenesis in the coculture of
      mouse marrow cells and NB-19 cells, we performed reverse transcription-PCR
      analysis and revealed the increased expression of receptor activator of nuclear
      factor kappaB ligand (RANKL) in the coculture compared with the culture of bone
      marrow cells alone. Interleukin-1alpha and cyclooxygenase-2 expression in the
      murine marrow cells was also increased in the presence of NB-19 cells. To further
      study the role of RANKL in the OC-like cell formation in the coculture of NB-19
      cells and murine marrow cells, an expression vector encoding the active portion
      of the murine osteoprotegerin, which is the native inhibitor of RANKL action, was
      constructed and introduced into COS-7 cells. The conditioned media of the COS-7
      cells transfected with the osteoprotegerin expression vector effectively blocked
      OC-like cell formation in the coculture of the bone marrow cells and NB-19 cells.
      These results suggested that in the bone microenvironment of NB-19-bearing mice,
      the stimulated expression of RANKL plays an important role in OC formation,
      leading to osteolytic bone metastasis.

PMID- 11245478
TI  - Anticancer agents sensitize tumor cells to tumor necrosis factor-related
      apoptosis-inducing ligand-mediated caspase-8 activation and apoptosis.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a new cytokine
      that was proposed to specifically induce apoptosis of cancer cells. In tumor
      cells that are resistant to the cytokine, subtoxic concentrations of
      chemotherapeutic drugs can restore the response to TRAIL. The present study
      further explores the mechanisms that determine tumor cell sensitivity to TRAIL by
      comparing four human colon carcinoma cell lines We show that colon cancer cell
      sensitivity to TRAIL-induced apoptosis and cytotoxicity correlates with the
      expression of the death receptors TRAIL-R1 and TRAIL-R2 at the cell surface, as
      determined by now cytometry, whereas the two decoy receptors TRAIL-R3 and TRAIL
      R4 can be detected only in permeabilized cells. Clinically relevant
      concentrations of cisplatin and doxorubicin sensitize the most resistant colon
      cancer cell lines to TRAIL-induced cell death without modifying the expression
      nor the localization of TRAIL receptors in these cells. TRAIL induces the
      activation of procaspase-8 and triggers caspase-dependent apoptosis off colon
      cancer cells. Cytotoxic drugs lower the signaling threshold required for TRAIL
      induced procaspase-8 activation. In turn, caspase-8 cleaves Bid, a BH3 domain
      containing proapoptotic molecule of the Bcl-2 family and activates effector
      caspases. Together, these data indicate that chemotherapeutic drugs sensitize
      colon tumor cells to TRAIL-mediated caspase-8 activation and apoptosis.

PMID- 11245479
TI  - Identification of CGA as a novel estrogen receptor-responsive gene in breast
      cancer: an outstanding candidate marker to predict the response to endocrine
      therapy.
AB  - The estrogen receptor (ER) status of breast tumors is used to identify patients
      who may respond to endocrine agents such as tamoxifen. However, ER status alone
      is not perfectly predictive, and there is a pressing need for more reliable
      markers of endocrine responsiveness. Here, we identified the well-known CGA gene
      (coding for the alpha subunit of glycoprotein hormones) as a new ERalpha
      responsive gene in human breast cancer cells. We used a real-time quantitative
      reverse transcription-PCR assay to quantify CGA mRNA copy numbers in a large
      series of breast tumors. CGA overexpression (> 10 SD above the mean for normal
      breast tissues) was observed in 44 of 131 (33.6%) breast tumor RNAs, ranging from
      20 to 16,500 times the level in normal breast tissues; the highest levels of CGA
      gene expression were close to those observed in placenta. Significant links were
      observed between CGA gene overexpression and Scarff-Bloom-Richardson
      histopathological grade I+II (P = 0.015), and progesterone (P = 0.0009) and
      estrogen (P < 10(-7)) receptor positivity, which suggested that CGA is a marker
      of low tumor aggressiveness. We observed CGA mRNA overexpression in 44 of 90
      (48.9%) ERalpha-positive tumors and in none of the 41 ERalpha-negative tumors.
      Immunohistochemical studies demonstrated that human chorionic gonadotropin alpha
      protein was strictly limited to ERalpha-positive tumor cells. Overexpression of
      the CGA gene was not accompanied by overexpression of the CGB gene. Our results
      also suggest that CGA could be a more reliable marker than PS2 and PR for ERalpha
      functionality and, thus, for endocrine responsiveness. Moreover, the CGA marker
      has the added value of dichotomizing ERalpha-positive patients into two subgroups
      of similar size. Specific antibodies directed to secreted human chorionic
      gonadotropin alpha protein are commercially available, thus facilitating the
      future application of this marker to the clinical management of breast cancer.

PMID- 11245480
TI  - DNA fragments in the blood plasma of cancer patients: quantitations and evidence
      for their origin from apoptotic and necrotic cells.
AB  - Increased levels of DNA fragments have frequently been found in the blood plasma
      of cancer patients. Published data suggest that only a fraction of the DNA in
      blood plasma is derived from cancer cells. However, it is not known how much of
      the circulating DNA is from cancer or from noncancer cells. By quantitative
      methylation-specific PCR of the promoter region of the CDKN2A tumor suppressor
      gene, we were able to quantify the fraction of plasma DNA derived from tumor
      cells. In the plasma samples of 30 unselected cancer patients, we detected
      quantities of tumor DNA from only 3% to as much as 93% of total circulating DNA.
      We investigated possible origins of nontumor DNA in the plasma and demonstrate
      here a contribution of T-cell DNA in a few cases only. To investigate the
      possibility that plasma DNA originates from apoptotic or necrotic cells, we
      performed studies with apoptotic (staurosporine) and necrotic (staurosporine plus
      oligomycin) cells in vitro and with mice after induction of apoptotic (anti-CD95)
      or necrotic (acetaminophen) liver injury. Increasing amounts of DNA were found to
      be released in the supernatants of cells and in the blood plasma samples of
      treated animals. A clear discrimination of apoptotic and necrotic plasma DNA was
      possible by gel electrophoresis. The same characteristic patterns of DNA
      fragments could be identified in plasma derived from different cancer patients.
      The data are consistent with the possibility that apoptotic and necrotic cells
      are a major source for plasma DNA in cancer patients.

PMID- 11245481
TI  - Prognostic significance of polysialic acid expression in resected non-small cell
      lung cancer.
AB  - Polysialic acid (PSA) is a carbohydrate attached mainly to the neural cell
      adhesion molecule. Because PSA is composed of a linear homopolymer of alpha-2-8
      linked sialic acid residues and has a large negative charge, the presence of PSA
      attenuates the adhesive property of neural cell adhesion molecule and increases
      cellular motility. In an earlier study, we demonstrated that PSA and STX, a
      polysialyltransferase, were associated with tumor progression in non-small cell
      lung cancer (NSCLC) (F. Tanaka et al., Cancer Res., 60: 3072-3080, 2000).
      Therefore, in the present study, to assess the prognostic significance of PSA in
      resected NSCLC, a total of 236 patients who underwent complete resection for
      pathological (p)-stage I-IIIa disease were reviewed retrospectively. PSA was
      expressed in 44 of 236 (18.6%) patients, and the expression was correlated with p
      stage disease. For all p-stage patients, 5-year survival rates for those with PSA
      positive and PSA-negative tumors were 52.1% and 71.3%, respectively,
      demonstrating a significantly worse prognosis for the PSA-positive patients (P =
      0.012). Analysis for only p-stage I patients also demonstrated a significantly
      worse prognosis for the PSA-positive patients; 5-year survival rates of the PSA
      positive and the PSA-negative patients were 45.1% and 83.5%, respectively, (P <
      0.001). In addition, there proved to be no difference in the postoperative
      survival among p-stage I, II, and IIIa patients when PSA expression was positive.
      Multivariate analysis confirmed that PSA expression was an independent factor to
      predict poor prognosis in resected NSCLC. These results suggested that PSA could
      be an important clinical marker and that preoperative induction and/or
      postoperative adjuvant therapies should be performed for PSA-positive NSCLC, even
      if the disease is classified as p-stage I.

PMID- 11245482
TI  - Geldanamycin abrogates ErbB2 association with proteasome-resistant beta-catenin
      in melanoma cells, increases beta-catenin-E-cadherin association, and decreases
      beta-catenin-sensitive transcription.
AB  - Beta-catenin undergoes both serine and tyrosine phosphorylation. Serine
      phosphorylation in the amino terminus targets beta-catenin for proteasome
      degradation, whereas tyrosine phosphorylation in the COOH terminus influences
      interaction with E-cadherin. We examined the tyrosine phosphorylation status of
      beta-catenin in melanoma cells expressing proteasome-resistant beta-catenin, as
      well as the effects that perturbation of beta-catenin tyrosine phosphorylation
      had on its association with E-cadherin and on its transcriptional activity. Beta
      catenin is tyrosine phosphorylated in three melanoma cell lines and associates
      with both the ErbB2 receptor tyrosine kinase and the LAR receptor tyrosine
      phosphatase. Geldanamycin, a drug which destabilizes ErbB2, caused rapid cellular
      depletion of the kinase and loss of its association with beta-catenin without
      perturbing either LAR or beta-catenin levels or LAR/beta-catenin association.
      Geldanamycin also stimulated tyrosine dephosphorylation of beta-catenin and
      increased beta-catenin/E-cadherin association, resulting in substantially
      decreased cell motility. Geldanamycin also decreased the nuclear beta-catenin
      level and inhibited beta-catenin-driven transcription, as assessed using two
      different beta-catenin-sensitive reporters and the endogenous cyclin D1 gene.
      These findings were confirmed by transient transfection of two beta-catenin point
      mutants, Tyr-654Phe and Tyr-654Glu, which, respectively, mimic the
      dephosphorylated and phosphorylated states of Tyr-654, a tyrosine residue
      contained within the beta-catenin-ErbB2-binding domain. These data demonstrate
      that the functional activity of proteasome-resistant beta-catenin is regulated
      further by geldanamycin-sensitive tyrosine phosphorylation in melanoma cells.

PMID- 11245483
TI  - Identification of genes involved in human urothelial cell-matrix interactions:
      implications for the progression pathways of malignant urothelium.
AB  - Interactions between epithelial cells and the extracellular matrix are central to
      tissue homeostasis and have a dynamic role in tissue remodeling and repair.
      Regulation of these pathways is balanced by positive and negative feedback
      elements, many of which have been implicated in the pathways of malignant
      progression. We have used differential display to identify genes that are up
      regulated in normal human urothelial cells in response to exposure to
      extracellular matrix proteins (Matrigel) in vitro. This approach has identified
      genes that have key roles in cell-cell and cell-matrix interactions and that have
      been implicated in the progression of carcinomas of urothelial or other
      epithelial cell origins. One confirmed but unknown differentially expressed
      sequence was used to isolate a full-length gene, MIG-C4, from a human urothelial
      cDNA library. This gene was found to encode a novel urokinase plasminogen
      activator receptor-like member of the Ly-6 family of glycosyl
      phosphatidylinositol-anchored glycoproteins, and was identified as the human
      homologue of the rat metastasis-associated C4.4A gene. By in situ hybridization,
      MIG-C4 was expressed variably in normal urothelium and intensely in the tumor
      component of some noninvasive superficial lesions and in invasive and metastatic
      urothelial cancers. Thus, our approach has identified previously nonimplicated
      gene products involved in normal urothelium-matrix interactions that could be
      tumor-invasion or suppressor-gene targets in the development of invasive and
      metastatic tumor phenotypes.

PMID- 11245484
TI  - Catalytic cleavage of the androgen-regulated TMPRSS2 protease results in its
      secretion by prostate and prostate cancer epithelia.
AB  - We identified TMPRSS2 as a gene that is down-regulated in androgen-independent
      prostate cancer xenograft tissue derived from a bone metastasis. Using specific
      monoclonal antibodies, we show that the TMPRSS2-encoded serine protease is
      expressed as a Mr 70,000 full-length form and a cleaved Mr 32,000 protease
      domain. Mutation of Ser-441 in the catalytic triad shows that the proteolytic
      cleavage is dependent on catalytic activity, suggesting that it occurs as a
      result of autocleavage. Mutational analysis reveals the cleavage site to be at
      Arg-255. A consequence of autocatalytic cleavage is the secretion of the protease
      domain into the media by TMPRSS2-expressing prostate cancer cells and into the
      sera of prostate tumor-bearing mice. Immunohistochemical analysis of clinical
      specimens demonstrates the highest expression of TMPRSS2 at the apical side of
      prostate and prostate cancer secretory epithelia and within the lumen of the
      glands. Similar luminal staining was detected in colon cancer samples. Expression
      was also seen in colon and pancreas, with little to no expression detected in
      seven additional normal tissues. These data demonstrate that TMPRSS2 is a
      secreted protease that is highly expressed in prostate and prostate cancer,
      making it a potential target for cancer therapy and diagnosis.

PMID- 11245485
TI  - Drug resistance induced by ouabain via the stimulation of MDR1 gene expression in
      human carcinomatous pulmonary cells.
AB  - The inhibition of the Na+/K+-ATPase by cardiotonic drugs like ouabain deeply
      perturbs both the properties of the cell membrane and the ionic composition of
      the cytoplasm and hence alters fundamental cell reactions. These three types of
      reactions may be involved in the stimulation of multidrug resistance 1 (MDR-1)
      gene expression and the synthesis of permeability glycoprotein [P-glycoprotein (P
      gp)]. We have determined whether ouabain, which binds to an extracellular motif
      of the Na+/K+-ATPase, stimulates MDR-1 gene expression by measuring both mRNA and
      protein and whether the resulting P-gp extrudes hydrophobic compounds and causes
      resistance to antimitotic agents. The experiments were performed on Calu-3 cells,
      a human cell line from a pulmonary carcinoma. Northern blotting showed that
      treating the cells with submicromolar concentrations of ouabain stimulated MDR-1
      gene expression within 24 h. The ouabain-induced stimulation of MDR-1 expression
      was not restricted to Calu-3 cells but also occurred in human carcinomatous colon
      (T-84 and HT-29) and hepatic (H7V3) cells. However, it is not ubiquitous because
      it was not found in HeLa cells. The stimulation was reproduced by other Na+/K+
      ATPase inhibitors and occurred via enhanced gene transcription, apparently due to
      the increased cytosolic calcium concentration. Ouabain also increased the
      membrane content of P-gp, as detected by immunoblotting and immunohistology. We
      have developed a microvideo assay based on the properties of acetoxymethyl ester
      calcein and calcein to show that this P-gp extruded the hydrophobic acetoxymethyl
      ester calcein. Ouabain also caused the Calu-3 cells to become resistant to
      doxorubicin and vinblastine. Thus, although ouabain acts extracellularly, it may
      stimulate MDR-1 gene expression and P-gp synthesis and make cells resistant to
      hydrophobic cytotoxic compounds.

PMID- 11245486
TI  - Overexpression of BCL-X(L) underlies the molecular basis for resistance to
      staurosporine-induced apoptosis in PC-3 cells.
AB  - We have reported previously that among human prostate cancer cell lines LNCaP but
      not PC-3 cells undergo apoptosis after treatment with the protein kinase
      inhibitor staurosporine (STS). We have now further investigated this model to
      uncover the molecular mechanism causing resistance to STS-induced apoptosis in PC
      3 cells. S-100 lysates of both cell lines showed biochemical changes typical of
      apoptosis after the addition of cytochrome c and dATP, suggesting that the
      postmitochondrial phase of apoptosis was intact. Upon addition of STS, the
      proapoptotic molecules Bax and Bad became predominantly mitochondrial in both
      cell lines. This, in turn, was followed by loss of mitochondrial transmembrane
      potential, translocation of cytochrome c to the cytosol, activation of caspase-9,
      -3, and -7, and cleavage of the apoptotic targets, DNA fragmentation factor and
      poly(ADP-ribose) polymerase, in LNCaP but not in PC-3 cells. Components of the
      mitochondrial permeability transition pore, adenine nucleotide transporter and
      voltage-dependent anion channel, were normally expressed in the correct
      subcellular fraction of both cell lines. Overexpression of the proapoptotic
      proteins Bax and Bad, fused to a green fluorescent protein but not of green
      fluorescent protein alone, induced apoptosis in >80% of PC-3 cells. These
      experiments suggested that a factor protecting the mitochondria of PC-3 cells
      mediates resistance to STS-induced apoptosis. A wide search among the
      antiapoptotic Bcl-2 family members was performed, and Bcl-X(L) was found to be
      overexpressed in PC-3 cells. Experiments down-regulating Bcl-X(L) expression by
      using the tyrosine kinase inhibitor genistein, sodium butyrate, or an antisense
      Bcl-X(L) oligonucleotide restored sensitivity to apoptosis in PC-3 cells. Thus,
      Bcl-X(L) overexpression is one of the mediators of resistance to STS-induced
      apoptosis in the prostate cancer cell line PC-3.

PMID- 11245487
TI  - Anoikis and metastatic potential of cloudman S91 melanoma cells.
AB  - Anoikis is a form of apoptosis induced in normal cells as a result of loss of
      their adhesion to substrate. In the present study, we have tested whether tumor
      cells are also sensitive to anoikis and whether selection of tumor cells for
      resistance to anoikis could increase their metastatic ability. In vitro cultured
      Cloudman S91 melanoma cells are strongly adherent to the plastic. Prevention of
      their adherence by rocking or by covering culture plates with
      polyhydroxyethylmethacrylate resulted in induction of anoikis and death of almost
      all cells. Their death was prevented in the presence of caspase inhibitor Z-Val
      Ala-Asp-fluoromethyl ketone. To select anoikis-resistant cells, S91 cells
      floating in the culture medium were sequentially isolated and transferred for
      seven generations. As a result, a new subline of S91 cells capable of growing in
      free cell suspension was selected. These S91 nonadherent (S91Nadh) cells were
      completely resistant to anoikis and manifested higher metastatic ability than
      S91Adh cells. Anoikis resistance of S91Nadh cells was not attributable to their
      resistance to other apoptotic signals in vitro, and they showed no increase in
      their survival in vivo in the lungs after i.v. inoculation. Increased metastatic
      potential of the anoikis-resistant S91Nadh cells was associated with various
      phenotypic changes, including increased proliferation and loss of VLA-4 integrin
      expression because of down-regulation of the VLA-49alpha (CLD49d) gene. In
      parallel, they showed a reduction in homotypic aggregation and binding to
      endothelial cells, increased Matrigel invasiveness, and decreased matrix
      metalloproteinase-2 and matrix metalloproteinase-9 activity that paralleled up
      regulation of the TIMP-1 gene. S91Nadh cells also manifested changes in cell
      surface carbohydrates, such as appearance of alpha-galactosyl epitopes as a
      result of up-regulation of the alpha1,3-galactosyltransferase gene and
      concomitant reduction in cell membrane sialylation. Thus, selection of S91
      melanoma cells for anoikis resistance resulted in an increase in their metastatic
      potential in parallel with multiple alterations in their phenotypic properties.

PMID- 11245488
TI  - Inhibition of fibroblast growth factor/fibroblast growth factor receptor activity
      in glioma cells impedes tumor growth by both angiogenesis-dependent and 
      independent mechanisms.
AB  - We undertook a series of systematic studies to address the role of fibroblast
      growth factor/fibroblast growth factor receptor (FGF/FGFR) activity in tumor
      growth and angiogenesis. We expressed dominant-negative FGFR2 (FGFR2-DN) or FGFR1
      (FGFR1-DN) in glioma C6 cells by using constitutive or tetracycline-regulated
      expression systems. Anchorage-dependent or independent growth was inhibited in
      FGFR-DN-expressing cells. Tumor development after xenografting FGFR-DN-expressing
      cells in immunodeficient mice or after transplantation in rat brain was strongly
      inhibited. Quantification of microvessels demonstrated a significant decrease in
      vessel density in tumors derived from FGFR-DN-expressing cells. Furthermore, in a
      rabbit corneal assay, the angiogenic response after implantation of FGFR-DN
      expressing cells was decreased. In tumors expressing FGFR-DN, vascular
      endothelial growth factor expression was strongly inhibited as compared with
      control tumor. These results indicate that inhibition of FGF activity may
      constitute a dominant therapeutic strategy in the treatment of FGF-producing
      cerebral malignancies and may disrupt both angiogenesis-dependent and 
      independent signals required for glioma growth and invasion.

PMID- 11245489
TI  - Up-regulation of vascular endothelial growth factor in breast cancer cells by the
      heregulin-beta1-activated p38 signaling pathway enhances endothelial cell
      migration.
AB  - Heregulin (HRG) belongs to a family of polypeptide growth factors that bind to
      receptor tyrosine kinases ErbB3 and ErbB4. HRG binding induces ErbB3 and ErbB4
      heterodimerization with ErbB2, activating downstream signal transduction.
      Vascular endothelial growth factor (VEGF) is a primary regulator of physiological
      angiogenesis and is a major mediator of pathological angiogenesis, such as tumor
      associated neovascularization. In this study, we demonstrate that HRG-beta1
      increased secretion of VEGF from breast cancer cells in a time- and dosage
      dependent manner and that this increase resulted from up-regulation of VEGF mRNA
      expression via transcriptional activation of the VEGF promoter. Deletion and
      mutational analysis revealed that a CA-rich upstream HRG response element located
      between nucleotide-2249 and -2242 in the VEGF promoter mediated HRG-induced
      transcriptional up-regulation of VEGF. While investigating the downstream
      signaling pathways involved in HRG-mediated up-regulation of VEGF, we found that
      HRG activated extracellular signal-regulated protein kinases, Akt kinase, and p38
      mitogen-activated protein kinase (MAPK). However, only the specific inhibitor of
      p38 MAPK (SB203580), not extracellular signal-regulated kinase inhibitor PD98059
      nor the inhibitor of phosphatidylinositol 3-kinase-Akt pathway (Wortmannin),
      blocked the up-regulation of VEGF by HRG. The HRG-stimulated secretion of VEGF
      from breast cancer cells resulted in increased migration of murine lung
      endothelial cells, an activity that was inhibited by either VEGF-neutralizing
      antibody or SB203580. These results show that HRG can activate p38 MAPK to
      enhance VEGF transcription via an upstream HRG response element, leading to
      increased VEGF secretion and angiogenic response in breast cancer cells.

PMID- 11245491
TI  - Mechanism of functional inactivation of a Li-Fraumeni syndrome p53 that has a
      mutation outside of the DNA-binding domain.
AB  - The majority of p53 mutations are located in the DNA-binding domain of the
      protein. However, recently a family suffering from Li-Fraumeni syndrome (LFS) has
      been discovered, some of whom harbor a p53 mutation in exon 4, outside of the
      core domain. How this mutation affects p53 function and subsequently leads to
      malignant transformation is not yet clear. Interestingly, the p53 mutation found
      in this LFS family is localized to the p53 region that we have recently
      identified as necessary for Mdm2-mediated p53 degradation. We therefore
      endeavored to study further the LFS-associated p53 mutation at the molecular
      level by creating an equivalent lesion in a p53 expression construct and
      functionally characterizing it. Here we demonstrate that a mutation in this
      region is associated not only with resistance of the mutant p53 to Mdm2-mediated
      degradation, but also with an impaired response of mutant protein to DNA damage.
      In addition, the p53(LFS) mutant was found to be defective in its transactivation
      function, which correlated with its inability to suppress cell growth and to
      induce apoptosis. The molecular basis for p53(LFS) functional impairment appears
      to be its predominantly cytoplasmic localization caused by faulty nuclear import
      mechanism, which, at least in part, resulted from the mutant's decreased affinity
      to importin.

PMID- 11245490
TI  - Chemoprevention of intestinal polyposis in the Apcdelta716 mouse by rofecoxib, a
      specific cyclooxygenase-2 inhibitor.
AB  - Mutations in the human adenomatous polyposis (APC) gene are causative for
      familial adenomatous polyposis (FAP), a rare condition in which numerous colonic
      polyps arise during puberty and, if left untreated, lead to colon cancer. The APC
      gene is a tumor suppressor that has been termed the "gatekeeper gene" for colon
      cancer. In addition to the 100% mutation rate in FAP patients, the APC gene is
      mutated in >80% of sporadic colon and intestinal cancers. The Apc gene in mice
      has been mutated either by chemical carcinogenesis, resulting in the Min mouse
      Apcdelta850, or by heterologous recombination, resulting in the Apcdelta716 or
      Apedelta1368 mice (M. Oshima et al., Proc. Natl. Acad. Sci. USA, 92: 4482-4486,
      1995). Although homozygote Apc-/- mice are embryonically lethal, the
      heterozygotes are viable but develop numerous intestinal polyps with loss of Apc
      heterozygosity within the polyps (M. Oshima et al., Proc. Natl. Acad. Sci. USA,
      92: 4482-4486, 1995). The proinflammatory, prooncogenic protein cyclooxygenase
      (COX)-2 has been shown to be markedly induced in the Apcdelta716 polyps at an
      early stage of polyp development (M. Oshima et al., Cell, 87: 803-809, 1996). We
      demonstrate here that treatment with the specific COX-2 inhibitor rofecoxib
      results in a dose-dependent reduction in the number and size of intestinal and
      colonic polyps in the Apcdelta716 mouse. The plasma concentration of rofecoxib
      that resulted in a 55% inhibition of polyp number and an 80% inhibition of polyps
      > 1 mm in size is comparable with the human clinical steady-state concentration
      of 25 mg rofecoxib (Vioxx) taken once daily (A. Porras et al., Clin. Pharm.
      Ther., 67: 137, 2000). Polyps from both untreated and rofecoxib- or sulindac
      treated Apcdelta716 mice expressed COX-1 and -2, whereas normal epithelium from
      all mice expressed COX-1 but minimal amounts of COX-2. Polyps from either
      rofecoxib- or sulindac-treated mice had lower rates of DNA replication, expressed
      less proangiogenic vascular endothelial-derived growth factor and more membrane
      bound beta-catenin, but showed unchanged nuclear localization of this
      transcription factor. This study showing the inhibition of polyposis in the
      Apcdelta716 mouse suggests that the specific COX-2 inhibitor rofecoxib (Vioxx)
      has potential as a chemopreventive agent in human intestinal and colon cancer.

PMID- 11245493
TI  - Identification of a proviral structure in human breast cancer.
AB  - Involvement of a virus similar to mouse mammary tumor virus (MMTV) in human
      breast cancer has long been postulated but never demonstrated. We have detected
      by PCR a 660-bp sequence similar to the env gene of MMTV but not to the known
      endogenous viruses, in 38% of human breast cancers examined (Wang et al., Cancer
      Res., 55: 5173-5179, 1995). This sequence was expressed in 66% of the env
      positive tumors as detected by reverse transcription-PCR (Wang et al., Clin.
      Cancer Res., 4: 2565-2568, 1998). In this article we report the amplification of
      a whole proviral structure from each of two human breast carcinomas that were env
      positive. Using nested extra-long PCR and primers from specific MMTV sequences,
      overlapping env-long terminal repeat (LTR), LTR-gag, gag-pol, and pol-env
      segments were successfully amplified. The 9.9-kb provirus is 95% homologous to
      MMTV but only 57% to human endogenous retrovirus K10 in 3.5 kb of the gag and pol
      genes. The provirus displays typical features of a replication competent virus,
      plus the open reading frame for the superantigen and the glucocorticoid
      responsive element. Fluorescence in situ hybridization with a 2.7-kb env-LTR
      sequence of an env-positive breast cancer cell line revealed that the sequence is
      inserted in several chromosomes but not in chromosomes from normal breast cells.
      The origin of the MMTV-like sequences is uncertain. Because they are undetectable
      in normal tissues, because the similarity between the two isolates is high (96%),
      and because they maintain open reading frames, they appear to be exogenous.

PMID- 11245492
TI  - A novel serine-dependent proteolytic activity is responsible for truncated signal
      transducer and activator of transcription proteins in acute myeloid leukemia
      blasts.
AB  - Hematopoietic cytokine receptor signaling involves activation of signal
      transducer and activator of transcription (STAT) proteins that are thought to
      control cellular differentiation. Truncated STAT isoforms (beta forms, rather
      than the normal alpha forms) have been described and found to block the normal
      signaling function of the alpha isoforms. We recently demonstrated STATbeta
      isoforms in bone marrow samples from 21 of 27 (78%) acute myeloid leukemia (AML)
      patients. We sought to determine the mechanism by which the STATbeta forms were
      generated. Samples from eight newly diagnosed AML patients were studied; four
      expressed predominantly STATalpha, and four expressed predominantly STATbeta. The
      reverse transcription-PCR generated identical products in the two groups,
      suggesting that alternate mRNA splicing is not responsible for the genesis of
      STATbeta. Extracts from cells expressing predominantly STATbeta incubated with
      cell extracts from the MO7E cell line, which expresses predominantly STATa,
      caused a decrease of the alpha isoforms and an increase of the beta isoforms,
      suggesting the presence of proteolytic activity. This proteolytic activity was:
      (a) specific for STAT3 and STAT5, but not for STAT6; (b) serine dependent; (c)
      equally present in nuclear and cytoplasmic fractions of the leukemic blasts; and
      (d) different than the activity detected in a murine hematopoietic cell line. The
      cleaved beta isoforms retained their DNA-binding activity. Because expression of
      truncated STATs may be involved in blocking differentiation of AML blasts,
      elucidation of the regulation of the proteolytic activity may contribute to our
      understanding of leukemogenesis.

PMID- 11245494
TI  - Does the location of deep venous thrombosis affect the risk of developing
      postphlebitic syndrome?

PMID- 11245495
TI  - Low pressure cardiac tamponade.

PMID- 11245496
TI  - Australian general practice: the need for leaders and vision.

PMID- 11245497
TI  - Ethical issues in placebo-controlled trials in Alzheimer disease.

PMID- 11245498
TI  - Evaluation of the role of positron emission tomography in oncology.

PMID- 11245500
TI  - Complementary therapies.

PMID- 11245499
TI  - Complementary therapies.

PMID- 11245501
TI  - "Floss and (nearly) die": dental floss and endocarditis.

PMID- 11245502
TI  - Herbal medicines for menopause: do they work and are they safe?

PMID- 11245503
TI  - Unravelling the Buteyko effect.

PMID- 11245504
TI  - Normocholesterolaemic dyslipidaemia: is there a role for fibrates?

PMID- 11245505
TI  - The effects of Chinese medicinal herbs on postmenopausal vasomotor symptoms of
      Australian women. A randomised controlled trial.
AB  - OBJECTIVE: To evaluate the effects of a defined formula of Chinese medicinal
      herbs (CMH) on menopausal symptoms. DESIGN: A double-blind randomised placebo
      controlled trial. METHODS: Between August 1998 and April 1999, 55 postmenopausal
      Australian women recruited from an urban population completed 12 weeks of
      intervention with either a defined formula of CMH (n = 28) or placebo (n = 27)
      taken twice daily as a beverage. MAIN OUTCOME MEASURES: The primary end-point was
      change in frequency of vasomotor events (hot flushes and night sweats). The
      secondary end-points were changes in score for the domains measured in the
      Menopause Specific Quality of Life (MENQOL) Questionnaire. RESULTS: There was a
      reduction in average weekly frequency of vasomotor events with CMH (-15%; 95% CI,
      -31% to +1%) and with placebo (-31%; 95% CI, -42% to -21%). The difference
      between groups favoured the use of placebo; however, this was not significant
      (P=0.09). Although significant reductions in scores for the various domains of
      the MENQOL Questionnaire were observed for both CMH and placebo, there were no
      significant differences between the two treatment groups for any domain. There
      was evidence for effect modification by previous use of natural therapies for the
      vasomotor, physical and sexual domains of the MENQOL Questionnaire: women with no
      prior use of natural therapies for their menopausal symptoms responded to
      therapy, whereas prior users did not. CONCLUSIONS: The defined formula of CMH was
      no more effective than placebo in reducing vasomotor episodes in Australian
      postmenopausal women, or in improving any of the four symptom domains in the
      MENQOL Questionnaire. Three of the MENQOL Questionnaire domains were modified by
      prior use of natural therapies. This finding has implications for future studies.

PMID- 11245506
TI  - The effects of carbon dioxide on exercise-induced asthma: an unlikely explanation
      for the effects of Buteyko breathing training.
AB  - OBJECTIVES: To examine the effect of breathing 3% CO2 on exercise-induced asthma
      (EIA), as a raised airway CO2 level is suggested to mediate the effects of
      Buteyko breathing training (BBT). DESIGN: Double-blind crossover study, using a
      standard laboratory-based exercise challenge, with EIA defined as a fall of 15%
      or greater in the forced expiratory volume in one second (FEV1) within 30 minutes
      of completing a standard exercise protocol. SUBJECTS: 10 adults with confirmed
      EIA. INTERVENTION: Air enriched with 3% CO2 during and for 10 minutes after
      exercise. OUTCOME MEASURES: Maximum percentage fall in FEV1 after exercise. Area
      under curve (AUC) of the decrease in FEV1 with time. RESULTS: Mean maximum fall
      in FEV1 was similar: 19.9% with air, and 26.9% with 3% CO2 (P = 0.12). The mean
      AUC for the total 30-minute post-exercise period was 355 for air and 520 for 3%
      CO2 (P = 0.07). After discontinuing the 3% CO2 at 10 minutes after exercise,
      there was a further and sustained fall in FEV1. Mean AUC for the period 10-30
      minutes post-exercise was significantly greater for CO2 than air (275 and 137,
      respectively [P = 0.02]). Mean minute ventilation was increased when subjects
      exercised breathing 3% CO2: 77.5 L/min for 3% CO2, compared with 68.7 L/min for
      air (P = 0.02). CONCLUSION: Breathing 3% CO2 during exercise does not prevent
      EIA. The shape of the FEV1 response curve after 3% CO2 suggests that a greater
      degree of EIA (because of increased minute ventilation during exercise) was
      opposed by a direct relaxant effect of CO2 on the airway. Increased airway CO2
      alone is an unlikely mechanism for the reported benefits of BBT; nevertheless,
      further study of the effects of voluntary hypoventilation in asthma is warranted.

PMID- 11245507
TI  - Use of fake tanning lotions in the South Australian population.
AB  - OBJECTIVE: To explore the relationship between the use of fake tanning lotions
      and repeated sunburn among South Australian adults, with a view to informing the
      Anti-Cancer Foundation of South Australia's (ACFSA) policy on fake tanning
      products. STUDY DESIGN: Population survey. PARTICIPANTS: 2005 South Australians
      aged 18 years or older, selected randomly from the electronic White Pages. MAIN
      OUTCOME MEASURES: Self-reported use of fake tanning lotions in the past 12
      months; frequency of sunburn over summer; and various sun-protective behaviours.
      RESULTS: 2,005 of the 2,536 eligible participants (79%) were surveyed by
      telephone. Fake tan use was most prevalent among women (15.9%), people aged 18-24
      years (15.4%), and people with household incomes above $40 000 per year (11.9%).
      Fake tan users were more likely than non-users to use sunscreens (81.3% v 56.5%;
      P < 0.001), but less likely to take other precautions such as wearing hats (40.9%
      v 51.0%; P = 0.04) and protective clothing (22.3% v 34.1%; P = 0.005). They were
      also more likely to report having been burnt more than once over summer (26.2% v
      16.5%; P = 0.025). Multivariate analysis indicates a statistically significant
      association between fake tan use and repeated sunburn (odds ratio, 2.07; 95%
      confidence interval, 1.17-3.69), which was independent of age, sex, skin type and
      sun-protection practices. CONCLUSION: Users of fake tanning products may be at
      greater risk of repeated sunburn. The ACFSA sees no justification at this stage
      for altering its present policy position of not actively promoting the use of
      fake tanning lotions as a means of reducing sunburn.

PMID- 11245508
TI  - Clinical effects of bites from formally identified spiders in tropical Northern
      Territory.
AB  - OBJECTIVE: To determine the types of spiders causing bites and the clinical
      effects of their bites in tropical Northern Territory (north of the town of
      Katherine). DESIGN: A prospective study of confirmed and suspected spider-bites
      and a retrospective analysis of data from a standardised, local database of
      spider- and snake-bites. Confirmed spider-bites were those in which there was a
      clear history of the bite, and the captured spider was identified by an
      arachnologist. SETTING: Emergency department of a teaching hospital. SUBJECTS AND
      DATA SOURCE: All subjects with confirmed or suspected spider-bite presenting to
      the Emergency Department or referred from August 1999 to August 2000, or
      identified from the database. RESULTS: Thirty-four subjects had a confirmed
      spider-bite from an identified spider: 25 in the prospective group and nine in
      the retrospective group. The spiders were Sparassidae (huntsman spider) (12
      bites), Missulena pruinosa (northern mouse spider) (7), Latrodectus (widow
      spider) (4), Araneidae (orb-weaver) (4), Salticidae (jumping spider) (4),
      Nemesidae (trapdoor spider) (1), Conothele (1) and Selenocosmia (whistling
      spider) (1). Clinical effects were local pain in 97% (severe in 29%), redness in
      47% and swelling in 24% of cases. Systemic effects occurred in three victims, two
      of whom were bitten by M. pruinosa. There were no cases of confirmed necrotic
      arachnidism. CONCLUSIONS: None of the spider-bites resulted in severe effects.
      Compared with data from other parts of Australia, different species were involved
      and latrodectism was uncommon. Our study highlighted the importance of correctly
      identifying the spider species.

PMID- 11245509
TI  - Australian medical patents granted in the United States in 1984-1999.
AB  - OBJECTIVE: To describe all medical patents granted in the United States to
      Australian-resident inventors between 1984 and 1999. DATA SOURCES: All patent
      data originated from the US Patent and Trademark Office. Data for 1984-1994 were
      compiled by CHI Research Inc, and data for 1995-1999 were obtained from the
      Community of Science website. MAIN OUTCOME MEASURES: Number of medical patents
      granted in the US to Australian-resident inventors; assignees (owners) of these
      medical patents; proportion of these medical patents related to biotechnology.
      RESULTS: From 1984 to 1999, 7835 utility patents were granted in the US to
      Australian-resident inventors. Of these, 1308 patents (17%) were identified as
      medical patents; 489 (37%) of these were biotechnology patents. Medical patents
      account for an increasing proportion of all US patents granted to Australian
      inventors, increasing from 10% in 1984 to 25% in 1999. Biotechnology accounted
      for an increasing proportion of medical patents, rising from 10% to 55% between
      1984 and 1999. More than half the medical patents are owned by commercial
      interests, and 33% by only 14 organisations, six of which are universities and
      their affiliated institutions. CONCLUSION: Only a few organisations account for
      most of the patenting of medical technology. The inventors and their
      organisations listed on medical patents could be canvassed when developing
      government policy and targeted for support in commercialising their medical
      technology.

PMID- 11245510
TI  - A primer of complementary and alternative medicine commonly used by cancer
      patients.
AB  - Complementary and alternative medicine (CAM) is frequently used by cancer
      patients, and many oncologists have limited knowledge of CAM. This article
      provides a brief, evidence-based introduction to several CAM treatments relevant
      in the context of cancer. "Alternative" diets, chiropractic, coffee enemas, ozone
      therapy, and shark cartilage seem to have little to offer cancer patients. The
      evidence for or against homoeopathy and spiritual healing is at present
      inconclusive. Acupuncture, aromatherapy, and meditation may be useful for
      nausea/vomiting, for mild relaxation, and for pain/anxiety, respectively. Herbal
      treatments offer no reasonable prospect of a cure (mistletoe), but could be
      useful as palliative treatments (eg, for depression [St John's wort] or anxiety
      [kava]). Our knowledge regarding the potential benefit and harm of CAM is
      insufficient.

PMID- 11245511
TI  - The moving of St Vincent's: a tale in two cities.
AB  - In Australia, demographic changes have seen the population of large cities move
      away from the inner city. This, combined with changes in healthcare delivery and
      the ageing of many tertiary teaching hospitals, has led governments to attempt to
      close, relocate or redefine the role of some institutions. Tracing the media
      coverage of two such events--the attempts to move St Vincent's hospitals in
      Sydney and Melbourne--provides some interesting insights into the challenges of
      resource allocation facing policymakers within the healthcare sector. Both
      hospitals were long-established, much-loved fixtures on inner-city sites with
      powerful connections to government and business. In Sydney, where the attempt was
      part of a larger plan to reallocate resources to the western suburbs, the
      announcement was met with 10 days of intense media coverage and scrutiny by lobby
      groups and the general public. By contrast, in Melbourne, no such announcement
      was made and the low-key reporting of support and opposition to the move occurred
      over two months. Both attempts failed. No matter how the debate is handled,
      radical changes involving long-established hospitals, powerful provider groups
      and loyal communities are very difficult to accomplish.

PMID- 11245512
TI  - "Ript from the womb": a short history of caesarean section.

PMID- 11245513
TI  - Patterns of musculoskeletal infection in childhood.

PMID- 11245514
TI  - Pyomyositis of the iliacus muscle in a child.
AB  - Pyomyositis is rarely seen in temperate climates. Typically, it presents with the
      formation of an abscess requiring surgical drainage and it has been reported as a
      differential diagnosis for septic arthritis of the hip. We describe the
      occurrence of pyomyositis of the iliacus muscle in a ten-year-old girl which was
      diagnosed by MRI and blood culture. Formation of an abscess did not occur despite
      marked focal inflammation and swelling of the muscle. Conservative treatment with
      antibiotics alone led to complete clinical and radiological resolution of the
      infection. We could find no previous description of pyomyositis in a child in the
      British orthopaedic literature. Orthopaedic surgeons, particularly those with a
      paediatric interest, should be aware of this condition and its presentation,
      diagnosis and treatment.

PMID- 11245515
TI  - Discitis in young children.
AB  - Discitis is uncommon in children and presents in different ways at different
      ages. It is most difficult to diagnose in the uncommunicative toddler of one to
      three years of age. We present 11 consecutive cases. The non-specific clinical
      features included refusal to walk (63%), back pain (27%), inability to flex the
      lower back (50%) and a loss of lumbar lordosis (40%). Laboratory tests were
      unhelpful and cultures of blood and disc tissue were negative. MRI reduces the
      diagnostic delay and may help to avoid the requirement for a biopsy. In 75% of
      cases it demonstrated a paravertebral inflammatory mass, which helped to
      determine the duration of the oral therapy given after initial intravenous
      antibiotics. At a mean follow-up of 21 months (10 to 40), all the spines were
      mobile and the patients free from pain. Radiological fusion occurred in 20% and
      was predictable after two years. At follow-up, MRI showed variable appearances:
      changes in the vertebral body usually resolved at 24 months and recovery of the
      disc was seen after 34 months.

PMID- 11245516
TI  - An unusual cause of sciatic pain.
AB  - We describe a 47-year-old woman with sciatic neuropathy caused by compression of
      the sacral plexus by posterior shift of the uterus.

PMID- 11245517
TI  - Obturator dislocation of the hip.
AB  - We describe two patients with obturator dislocation of the hip which was
      irreducible by described techniques of closed reduction. The first required open
      reduction using the iliofemoral approach with release of rectus femoris. The
      second was treated on a traction table which allowed disengagement of the head
      and, when combined with simultaneous lateral traction, adduction and gradual
      release of the longitudinal traction, facilitated a smooth reduction. Since the
      hip is stable in flexion, early mobilisation in an extension-limiting brace
      avoids the prolonged bed rest traditionally recommended for this injury.

PMID- 11245518
TI  - Spontaneous bifocal Clostridium septicum gas gangrene.
AB  - Clostridium septicum gas gangrene (myonecrosis) is an acutely painful and rapidly
      fatal infection occurring in the absence of trauma. Urgent surgery is essential
      both to control pain and to ensure survival. Most patients who develop this
      infection have an underlying malignancy and clinicians should be aware of this
      association. We present a case of bifocal myonecrosis which to our knowledge has
      not been reported previously.

PMID- 11245519
TI  - A comparison of bone remodelling around hydroxyapatite-coated, porous-coated and
      grit-blasted hip replacements retrieved at post-mortem.
AB  - We investigated the implant-bone interface around one design of femoral stem,
      proximally coated with either a plasma-sprayed porous coating (plain porous) or a
      hydroxyapatite porous coating (porous HA), or which had been grit-blasted
      (Interlok). Of 165 patients implanted with a Bimetric hip hemiarthroplasty
      (Biomet, Bridgend, UK) specimens were retrieved from 58 at post-mortem. We
      estimated ingrowth and attachment of bone to the surface of the implant in 21 of
      these, eight plain porous, seven porous HA and six Interlok, using image analysis
      and light morphometric techniques. The amount of HA coating was also quantified.
      There was significantly more ingrowth (p = 0.012) and attachment of bone (p <
      0.05) to the porous HA surface (mean bone ingrowth 29.093 +/- 2.019%; mean bone
      attachment 37.287 +/- 2.489%) than to the plain porous surface (mean bone
      ingrowth 21.762 +/- 2.068%; mean bone attachment 18.9411 +/- 1.971%). There was
      no significant difference in attachment between the plain porous and Interlok
      surfaces. Bone grew more evenly over the surface of the HA coating whereas on the
      porous surface, bone ingrowth and attachment occurred more on the distal and
      medial parts of the coated surface. No significant differences in the volume of
      HA were found with the passage of time. This study shows that HA coating
      increases the amount of ingrowth and attachment of bone and leads to a more even
      distribution of bone over the surface of the implant. This may have implications
      in reducing stress shielding and limiting osteolysis induced by wear particles.

PMID- 11245521
TI  - Evaluation of the viability of bone fragments.
AB  - We used laser Doppler flowmetry (LDF) to measure flux in cortical bone fragments
      as a method of determining their vascular status and viability. In an
      experimental tibial osteotomy measurements of flux were made from specific
      cortical sites both before and after osteotomy. Flux levels fell rapidly in non
      vascularised fragments and remained significantly reduced throughout the
      experiment. By contrast, those in vascularised fragments were significantly
      reduced one and two hours after the osteotomy but then increased. From three
      hours after the osteotomy there was no significant difference in flux levels
      between the vascularised fragments and proximal bone stock. We conclude that
      measurement of bone flux by LDF may have a role in the objective evaluation of
      the viability of bone fragments, but that further studies are required to
      validate the technique before its adoption in the management of the injured
      patient.

PMID- 11245520
TI  - Identification of caveolae and detection of caveolin in normal human osteoblasts.
AB  - Caveolae, specialised regions of the cell membrane which have been detected in a
      wide range of mammalian cells, have not been described in bone cells. They are
      plasmalemmal invaginations, 50 to 100 nm in size, characterised by the presence
      of the structural protein, caveolin, which exists as three subtypes. Caveolin-1
      and caveolin-2 are expressed in a wide range of cell types whereas caveolin-3 is
      thought to be a muscle-specific subtype. There is little information on the
      precise function of caveolae, but it has been proposed that they play an
      important role in signal transduction. As the principal bone-producing cell, the
      osteoblast has been widely studied in an effort to understand the signalling
      pathways by which it responds to extracellular stimuli. Our aim in this study was
      to identify caveolae and their structural protein caveolin in normal human
      osteoblasts, and to determine which subtypes of caveolin were present. Confocal
      microscopy showed staining which was associated with the plasma membrane.
      Transmission electron microscopy revealed the presence of membrane invaginations
      of 50 to 100 nm, consistent with the appearance of caveolae. Finally, we isolated
      protein from these osteoblasts, and performed Western blotting using anti
      caveolin primary antibodies. This revealed the presence of caveolin-1 and -2,
      while caveolin-3 was absent. The identification of these structures and their
      associated protein may provide a significant contribution to our further
      understanding of signal transduction pathways in osteoblasts.

PMID- 11245522
TI  - Influence of the vitamin D receptor alleles on human osteoblast-like cells.
AB  - We investigated the effect of vitamin D receptor gene (VDRG) polymorphism on the
      responsiveness to 1,25(OH)2D3 in human osteoblast-like cells. The cells were
      obtained from the femoral heads of 18 women with osteoarthritis of the hip. Three
      different restriction enzymes, BsmI, ApaI, and TaqI, were used to analyse the
      polymorphism. The genotypes of the 18 patients were bbAaTT (8), bbaaTT (6),
      BbAaTt (3), and BbAATt (1). Our findings showed that there were no differences
      according to the VDR genotype, but there was a statistically significant
      difference in the production of osteocalcin between BbAaTt and bbAaTT, and
      between BbAaTt and bbaaTT. Northern blot analysis of osteocalcin and VDR mRNA
      showed no significant differences among the three VDR genotypes. These findings
      suggest that VDR gene polymorphism affects the individual responsiveness of
      1,25(OH)2D3.

PMID- 11245523
TI  - Biocompatibility and osseointegration in osteoporotic bone.
AB  - We implanted nails made of titanium (Ti6Al4V) and of two types of glass ceramic
      material (RKKP and AP40) into healthy and osteopenic rats. After two months, a
      histomorphometric analysis was performed and the affinity index calculated. In
      addition, osteoblasts from normal and osteopenic bone were cultured and the
      biomaterials were evaluated in vitro. In normal bone the rate of osseointegration
      was similar for all materials tested (p < 0.5) while in osteopenic bone AP40 did
      not osseointegrate (p < 0.0005). In vitro, no differences were observed for all
      biomaterials when cultured in normal bone-derived cells whereas in osteopenic
      bone-derived cells there was a significant difference in some of the tested
      parameters when using AP40. Our findings suggest that osteopenic models may be
      used in vivo in the preclinical evaluation of orthopaedic biomaterials. We
      suggest that primary cell cultures from pathological models could be used as an
      experimental model in vitro.

PMID- 11245524
TI  - A long-term review of a modified Evans procedure.
AB  - Of 111 primary ankle ligament arthroplasties (modified Evans procedure) performed
      between 1983 and 1994, we were able to identify 89 patients (94 ankles) for
      follow-up. All were under 50 years of age. Two had died and one refused to co
      operate; 86 patients (91 ankles) were therefore reviewed, 25 by telephone and the
      remainder by clinical examination with all but three also undergoing radiological
      review. Of the 91 ankles, 70 had no or very mild pain and 72 had no or rare
      episodes of instability and when considered together only 59 (65%) had no or mild
      pain and minimal instability. The results were supported by the Karlsson grading
      system. Clinical examination showed that 17 of the 66 ankles examined had
      increased inversion, while 21 had some limitation of inversion. Early
      degenerative changes were seen in 11 ankles, although only four had subtalar
      changes. These results show that this procedure does not give universally good
      clinical results. Patient satisfaction, however, was high with 97.7% being
      willing to undergo the same procedure if their other ankle became similarly
      affected.

PMID- 11245525
TI  - BMP-4 of Xenopus laevis stimulates differentiation of human primary osteoblast
      like cells.
AB  - Since bone morphogenetic proteins (BMPs) are highly homologous, we investigated
      the hypothesis that recombinant BMP-4 of the genome of Xenopus laevis (rxBMP-4)
      may influence the proliferation or differentiation of human primary osteoblast
      like cells (HPOC), as occurs with recombinant human BMP (rhBMP-2). HPOC were
      incubated in the presence of either rxBMP-4, rhBMP-2 or basic fibroblast growth
      factor (rh-bFGF). The last two were used as positive controls and are known to
      induce differentiation or proliferation of HPOC, respectively. rxBMP-4 (50 ng/ml
      and 100 ng/ml) induced a differentiation of HPOC to almost the same extent as
      rhBMP-2, whereas the addition of rh-bFGF, applied in the same concentration,
      failed to have any influence on cell differentiation. rh-bFGF however, provoked
      an increase in cell proliferation of up to 150% when compared with non-stimulated
      HPOC, while rhBMP-2 and rxBMP-4 had no such effect. Our results indicate an
      equipotent effect of rhBMP-2 and rxBMP-4 obtained from Xenopus laevis on the
      differentiation and proliferation of human primary osteoblast-like cells.

PMID- 11245526
TI  - Anatomy of the medial femoral circumflex artery and its surgical implications.

PMID- 11245527
TI  - Nonunion of the femoral diaphysis.

PMID- 11245528
TI  - Nonunion of the femoral diaphysis.

PMID- 11245529
TI  - Does 'canal clearance' affect neurological outcome after thoracolumbar burst
      fractures?

PMID- 11245530
TI  - Thromboprophylaxis-which treatment for which patients?

PMID- 11245531
TI  - The distress and risk assessment method (DRAM).
AB  - Our aim was to judge the influence of preoperative psychological disturbance on
      the outcome of lumbar discectomy. We evaluated 66 patients, before and after
      operation, using a self-administered questionnaire. Disability was assessed using
      the Oswestry disability index and psychological disturbance the Distress and Risk
      Assessment Method (DRAM) score. Patients were classified as normal, at risk or
      distressed, and the outcome of surgery in the three groups was compared at a
      follow-up of six months. The mean self-reported preoperative disability was
      significantly higher in those with psychological disturbance. A total of 54
      patients (82%) returned completed postoperative questionnaires. Postoperative
      disability scores at six months were not significantly different in the three
      risk groups. Psychological disturbance improved after surgery. Our study suggests
      that the early outcome of lumbar discectomy is not affected by preoperative
      psychological disturbance. We conclude that a patient with a symptomatic
      prolapsed intervertebral disc should not be denied surgery on the basis of
      preoperative psychological assessment.

PMID- 11245532
TI  - The treatment of scoliosis in muscular dystrophy using modified Luque and
      Harrington-Luque instrumentation.
AB  - We have treated 101 patients with scoliosis secondary to muscular dystrophy over
      a 13-year period; 64 had Duchenne's muscular dystrophy, 33 spinal muscular
      atrophy and four congenital muscular dystrophy. The patients underwent a modified
      Luque (87) or Harrington-Luque instrumentation (14) combined with a limited Moe
      fusion in all except 27 cases. A mean of 13 levels was instrumented. The mean
      preoperative sitting Cobb angle was 84 degrees (10 to 150) and the mean
      postoperative angle 40 degrees (52% correction). Most patients (96%) were able to
      discard their braces and there was a high level of patient satisfaction (89.6%).
      Less correction was seen for severe curves, and there was a greater recurrence of
      postoperative pelvic tilt in those patients not instrumented to the sacrum.
      Although the incidence of minor or temporary complications was high, these
      occurred chiefly in the early high-risk patients with very severe curves and
      considerable pre-existing immobility.

PMID- 11245533
TI  - Arthroscopic medial meniscectomy on stable knees.
AB  - We reviewed 74 partial medial meniscectomies in 57 patients with stable knees, to
      assess the long-term functional and radiological outcome. The International Knee
      Documentation Committee score and the residual laxity were assessed in both
      knees. At the time of surgery the mean age of the patients was 36 +/- 11 years
      and the mean follow-up was 12 +/- 1 years. All had a limited medial meniscectomy.
      The anterior cruciate ligament was intact in all cases. The meniscal tear was
      vertical in 95% and complex in 5%. The posterior part of the meniscus was removed
      in 99%. A peripheral rim was preserved in all cases. After 12 years 95% of the
      patients were satisfied or very satisfied with their knee(s). Objectively, 57%
      had grade A function and 43% were grade B. The outcome correlated only with the
      presence of anterior knee pain at final follow-up. In the 49 cases of
      arthroscopic meniscectomy for which there was a contralateral normal knee there
      was narrowing of the 'joint-space' in 16% of the operated knees. There was no
      correlation between this and other parameters such as age or different meniscal
      pathologies.

PMID- 11245534
TI  - Substitutes for autologous bone graft in orthopaedic trauma.

PMID- 11245535
TI  - Femoral condylar lift-off in vivo in total knee arthroplasty.
AB  - We carried out weight-bearing video radiological studies on 40 patients with a
      total knee arthroplasty (TKA), to determine the presence and magnitude of femoral
      condylar lift-off. Half (20) had posterior-cruciate-retaining (PCR) and half (20)
      posterior-cruciate-substituting (PS) prostheses. The selected patients had
      successful arthroplasties with no pain or instability. Each carried out
      successive weight-bearing knee bends to maximum flexion, and the radiological
      video tapes were analysed using an interactive model-fitting technique. Femoral
      lift-off was seen at some increment of knee flexion in 75% of patients (PCR TKA
      70%; PS TKA 80%). The mean values for lift-off were 1.2 mm with a PCR TKA and 1.4
      mm with a PS TKA. Lift-off occurred mostly laterally with the PCR TKA, and both
      medially and laterally with the PS TKA. Separation between the femoral condyles
      and the articular surface of the tibia was recorded at 0 degrees, 30 degrees, 60
      degrees and 90 degrees of flexion. Femoral condylar lift-off may contribute to
      eccentric polyethylene wear, particularly in designs of TKA which have flatter
      condyles. Coronal conformity is an important consideration in the design of a
      TKA.

PMID- 11245536
TI  - Tourniquet-induced wound hypoxia after total knee replacement.
AB  - We have investigated whether the thigh tourniquet used during total knee
      replacement (TKR) influenced the development of postoperative wound hypoxia and
      was a cause of delayed wound healing. We allocated randomly 31 patients (31 TKRs)
      to one of three groups: 1) no tourniquet; 2) tourniquet inflated at low pressure
      (about 225 mmHg); and 3) tourniquet inflated to high pressure of about 350 mmHg.
      Wound oxygenation was measured using transcutaneous oxygen electrodes. In the
      first week after surgery, patients with a tourniquet inflated to a high pressure
      had greater wound hypoxia than those with a low pressure. Those without a
      tourniquet also had wound hypoxia, but the degree and duration were less
      pronounced than in either of the groups with a tourniquet. Use of a tourniquet
      during TKR can increase postoperative wound hypoxia, especially when inflated to
      high pressures. Our findings may be relevant to wound healing and the development
      of wound infection.

PMID- 11245537
TI  - The routine of surgical management reduces failure after unicompartmental knee
      arthroplasty.
AB  - A total of 10,474 unicompartmental knee arthroplasties was performed for medial
      osteoarthritis in Sweden between 1986 and 1995. We sought to establish whether
      the number of operations performed in an orthopaedic unit affected the incidence
      of revision. Three different implants were analysed: one with a high revision
      rate, known to have unfavourable mechanical and design properties; a prosthesis
      which is technically demanding with a known increased rate of revision; and the
      most commonly used unicompartmental device. Most of the units performed
      relatively few unicompartmental knee arthroplasties per year and there was an
      association between the mean number carried out and the risk of later revision.
      The effect of the mean number of operations per year on the risk of revision
      varied. The technically demanding implant was most affected, that most commonly
      used less so, and the outcome of the unfavourable design was not influenced by
      the number of operations performed. For unicompartmental arthroplasty, the long
      term results are related to the number performed by the unit, probably expressing
      the standards of management in selecting the patients and performing the
      operation.

PMID- 11245538
TI  - Arthrodesis of the knee after an infected arthroplasty using the Ilizarov method.
AB  - We treated 15 patients by arthrodesis of the knee after removal of an infected
      total knee arthroplasty, using an Ilizarov ring fixator. Eight had a failed
      arthrodesis by another technique. The mean age of the patients was 75 years, the
      mean duration of retention of the frame was 28 weeks, the mean treatment time 51
      weeks, and the mean follow-up 52 months. All but one knee fused at the first
      attempt, a rate of union of 93%. The incidence of complications related to
      treatment was 80%. The length of treatment and rates of complication were
      attributed to advanced age and the adverse local clinical factors in these
      patients. The Ilizarov method is a promising technique for achieving arthrodesis
      under these circumstances.

PMID- 11245539
TI  - Fractures of the tuberosity of the calcaneus.
AB  - We describe 24 fractures of the tuberosity of the calcaneus in 22 patients. Three
      were similar to the type of avulsion fracture which has been well-defined but the
      remainder represent a group which has been unrecognised previously. Using CT and
      operative findings we have defined the different patterns of fracture of the
      calcaneal tuberosity. Ten fractures extended into the subtalar joint, but did not
      fit the pattern of the common intra-articular fracture as described classically.
      We have defined a new pattern which consists of a fracture of the medial
      calcaneal process with a further fracture which separates the upper part of the
      tuberosity in the semicoronal plane. Non-operative treatment of displaced
      fractures resulted in a mis-shapen heel and a poor functional outcome. Open
      reduction and internal fixation with either a plate or compression screw did not
      give satisfactory fixation. We prefer to use an oblique lateral tension-band
      wire. This technique gave excellent fixation and we recommend it for the
      treatment of displaced fractures of the tuberosity of the calcaneus.

PMID- 11245540
TI  - Treatment of open fractures of the shaft of the tibia.
AB  - We have systematically reviewed the effect of alternative methods of
      stabilisation of open tibial fractures on the rates of reoperation, and the
      secondary outcomes of nonunion, deep and superficial infection, failure of the
      implant and malunion by the analysis of 799 citations on the subject, identified
      from computerised databases. Although 68 proved to be potentially eligible, only
      eight met all criteria for inclusion. Three investigators independently graded
      the quality of each study and extracted the relevant data. One study (n = 56
      patients) suggested that the use of external fixators significantly decreased the
      requirement for reoperation when compared with fixation with plates. The use of
      unreamed nails, compared with external fixators (five studies, n = 396 patients),
      reduced the risk of reoperation, malunion and superficial infection. Comparison
      of reamed with unreamed nails showed a reduced risk of reoperation (two studies,
      n = 132) with the reamed technique. An indirect comparison between reamed nails
      and external fixators also showed a reduced risk of reoperation (two studies)
      when using nails. We have identified compelling evidence that unreamed nails
      reduced the incidence of reoperations, superficial infections and malunions, when
      compared with external fixators. The relative merits of reamed versus unreamed
      nails in the treatment of open tibial fractures remain uncertain.

PMID- 11245541
TI  - The hyperabduction test.
AB  - We studied 100 fresh human shoulders in cadavers (mean age 76 years), and the
      range of passive abduction (RPA) in 100 volunteers with normal shoulders and in
      90 patients with instability of the joint, over a period of six years. The
      anatomical and clinical findings showed that passive abduction occurs within the
      glenohumeral joint only, is controlled by the inferior glenohumeral ligament and
      has a constant value in 95% of both shoulders in normal subjects. In patients
      with instability, 85% showed an RPA of over 105 degrees with 90 degrees in the
      contralateral shoulder. In the remaining patients a strongly positive
      apprehension test suggested a diagnosis of instability. An RPA of more than 105
      degrees is associated with lengthening and laxity of the inferior glenohumeral
      ligament.

PMID- 11245542
TI  - Percutaneous release of trigger digits.
AB  - We describe a safe and easy percutaneous technique for release of trigger finger
      using a specially designed knife. The A1 pulley is sectioned by a blade which has
      a hooked end. We released, percutaneously, 185 trigger fingers, including 62
      which were locked using this technique. Satisfactory results were achieved in 173
      (93.5%). There were no significant complications. We recommend this as a safe and
      effective outpatient procedure for those patients who have not responded
      successfully to conservative treatment, have longstanding symptoms or severe
      triggering.

PMID- 11245543
TI  - Treatment of nonunion of the scaphoid by a limited combined approach.
AB  - Seven patients with nonunion of the scaphoid were treated by a limited approach
      combining a palmar wedge graft with insertion of a dorsal (retrograde) Herbert
      screw through small incisions. All patients had palmar bone deficiency and a
      'difficult' proximal fragment. They were followed up for a minimum of 12 months
      (12 to 38). Radiological union was achieved in all. In five patients correction
      of instability of the dorsal intercalary segment which was present before
      operation, was achieved. On a wrist-scoring chart, all patients had an excellent
      or good rating. The limited combined approach allows correction of the deformity
      with rigid fixation and has the advantage of preserving most of the palmar
      ligaments.

PMID- 11245544
TI  - Trochanteric rotational osteotomy for osteonecrosis of the femoral head.
AB  - The rate of success of transtrochanteric rotational osteotomy for osteonecrosis
      of the femoral head may be improved if patients are preselected using MRI. We
      have used three criteria for selection for osteotomy (i) minor collapse of the
      infarcted area, loss of congruity or the crescent sign, without narrowing of the
      joint space or acetabular involvement (ii) patients younger than 55 years and
      with a painful hip (iii) patients with an intact area constituting an arc of more
      than 120 degrees between the central vertical line of the femoral head and the
      posterior or anterior margin of the necrotic portion as seen on a midsagittal
      MRI. Seventeen patients were selected, with a follow-up of more than 42 months. A
      bone scan four weeks after operation showed adequate perfusion of the proximal
      segment in all hips. The hip score of Merle d'Aubigne et al improved from 13.5
      points before operation to 17.2 points at the latest follow-up. Further collapse
      of the femoral head did not occur. The use of MRI instead of plain radiographs
      for the selection of patients has improved the success rate of transtrochanteric
      rotational osteotomy.

PMID- 11245545
TI  - Arthroscopic treatment of anterior impingement in the ankle.
AB  - We performed a prospective study to assess the long-term outcome of 57
      arthroscopic debridement procedures carried out to treat anterior impingement in
      the ankle. Using preoperative radiographs, we grouped patients according to the
      extent of their osteoarthritis (OA). The symptoms of those with grade-0 changes
      could be attributed to anterior soft-tissue impingement alone. Patients with
      grade-I disease had both anterior soft-tissue and osteophytic impingement, but no
      narrowing of the joint space. In those with grade-II OA, narrowing of the joint
      space was accompanied by osteophytic impingement. Radiographs taken before and
      after operation and at follow-up were compared to assess the recurrence of
      osteophytes and the progression of narrowing of the joint space. At a mean follow
      up of 6.5 years (5 to 8) all patients without OA had excellent or good results.
      There were excellent or good results in 77% of patients with grade-I OA, despite
      partial or complete recurrence of osteophytes in two-thirds. In most patients
      with grade-II OA, narrowing of the joint space had not progressed at follow-up.
      There was a notable improvement in pain in these patients, 53% of whom had
      excellent or good results. Although some osteophytes recurred, at long-term
      follow-up arthroscopic excision of soft-tissue overgrowths and osteophytes proved
      to be an effective way of treating anterior impingement of the ankle in patients
      who had no narrowing of the joint space.

PMID- 11245546
TI  - Therapeutic embolisation for postoperative haemorrhage after total arthroplasty
      of the hip and knee.
AB  - We describe three cases of postoperative haemorrhage, two after total hip and one
      after total knee replacement, treated by percutaneous embolisation. After
      diagnostic angiography, this is the preferred method for the treatment of
      postoperative haemorrhage due to the formation of a false aneurysm, after hip or
      knee arthroplasty. This procedure, carried out under local anaesthesia, has a low
      rate of complications and avoids the uncertainty of further surgical exploration.

PMID- 11245547
TI  - Primary subacute haematogenous osteomyelitis in children.
AB  - Between 1990 and 1998 we saw 21 children with primary subacute haematogenous
      osteomyelitis. Pain, swelling and a limp had been present for two to 12 weeks
      with little functional impairment. Laboratory tests were non-contributory. The
      lesions were classified radiologically into metaphyseal, diaphyseal, epiphyseal
      and vertebral. There were 24 sites involved, with most (20) being in the tibia;
      17 lesions were in the diaphysis, five in the metaphysis and two in the
      epiphysis. The diagnosis was confirmed histologically in all cases.
      Staphylococcus aureus was cultured in six patients. Healing occurred in all
      patients after treatment with antibiotics for six weeks and radiological
      improvement was seen after three to six months. Subacute osteomyelitis develops
      as a result of increased host resistance and decreased bacterial virulence. The
      radiological features can mimic various benign or malignant bone tumours and non
      pyogenic infections. Histological confirmation is necessary to avoid a delay in
      diagnosis.

PMID- 11245548
TI  - The changing epidemiology of acute and subacute haematogenous osteomyelitis in
      children.
AB  - We have reviewed the incidence of bacteriologically or radiologically confirmed
      acute haematogenous osteomyelitis in children under 13 years of age resident in
      the area of the Greater Glasgow Health Board between 1990 and 1997. In this
      period there was a fall of 44% in the incidence of both acute and subacute
      osteomyelitis, mainly involving the acute form (p = 0.005). This mirrors the
      decline of just over 50% previously reported in the same population between 1970
      and 1990. Using multiple regression analysis a decline in incidence of 0.185
      cases per 100,000 population per year was calculated for the 28-year period (p <
      0.001). Staphylococcus was the most commonly isolated pathogen (70%). Only 20% of
      patients required surgery and there was a low rate of complications (10%). In
      general, patients with a subacute presentation followed a benign course and there
      were no complications or long-term sequelae in this group. Haematogenous
      osteomyelitis in children in this area is becoming a rare disease with an annual
      incidence of 2.9 new cases per 100,000 population per year.

PMID- 11245549
TI  - Misoprostol for abortion up to 9 weeks' gestation in adolescents.
AB  - The objectives of the present clinical study were to evaluate the safety and
      efficacy of misoprostol (Cytotec) self-administered into the vagina for medical
      abortion in adolescents under the age of 18 years. After obtaining written
      consent from the patients and parents or guardians, a group of 150 adolescents
      with gestations between 35 and 63 days received 800 microg of vaginal misoprostol
      every 24 h, up to a maximum of three main doses, for abortion. Outcomes assessed
      included successful abortion (complete abortion without surgery), side-effects,
      decrease in hemoglobin, mean time of vaginal bleeding, mean expulsion time and
      mean time for the return of menses. Complete abortion occurred in 133/150 (88.7%,
      95% confidence interval 82-93) patients. The frequencies of nausea, vomiting and
      diarrhea were statistically significantly higher when compared to those obtained
      for adult females. Vaginal bleeding lasted for 12.7 +/- 5.7 days (median 12 days,
      range 1-23 days). The mean expulsion time was 6.8 +/- 2.4 h (median 6 h, range 3
      14 h) for those who aborted after the first misoprostol dose. The mean time for
      the return of menses, for those who aborted with misoprostol, was 34.7 +/- 3.4
      days. The mean decrease in hemoglobin was statistically significant (p = 0.001),
      but had no clinical relevance. Taking into account the high abortion rate
      obtained, we could conclude that misoprostol alone is a valid method for
      terminating unwanted pregnancies in adolescents under the age of 18 years.

PMID- 11245550
TI  - Contraception with a novel 'frameless' intrauterine levonorgestrel-releasing drug
      delivery system: a pilot study.
AB  - OBJECTIVE: To evaluate the contraceptive performance, acceptability, side-effects
      and adverse events of a novel 'frameless' intrauterine drug delivery system, the
      FibroPlant levonorgestrel intrauterine system, releasing 14 microg of
      levonorgestrel/day. An ancillary objective was to evaluate the effect of the new
      intrauterine system on menstrual blood loss. STUDY DESIGN: This was an open
      label, non-comparative, ongoing pilot study. Fifty-four insertions were performed
      by the first author in fertile women between 16 and 51 years of age for
      contraception. Eighteen of these women were fitted with the FibroPlant
      levonorgestrel intrauterine system for the treatment of excessive bleeding as
      well as for contraceptive purposes. Of these women, 12 had medium-to-large-sized
      uterine fibroids in addition to heavy menstrual flow. The follow-up period of the
      trial was between 6 and 16 months. RESULTS: At the time of study analysis the
      total number of woman-months was 464 and 21 women had had the FibroPlant
      levonorgestrel intrauterine system in place for more than 1 year. No pregnancies
      occurred. All women reported greatly reduced bleeding; however, no cases of
      amenorrhea resulting from endometrial suppression were encountered. Significant
      spotting was rare after the first 3 months following insertion. No complications
      (e.g. infection, expulsion or perforation) occurred. The FibroPlant
      levonorgestrel intrauterine system was well tolerated by all women involved in
      the study and no systemic hormonal side-effects were reported. CONCLUSIONS:
      Although the average age of the study subjects was 40 years, this preliminary
      study suggests that the FibroPlant levonorgestrel intrauterine system is an
      effective contraceptive. The FibroPlant levonorgestrel intrauterine system is
      also highly efficacious in controlling bleeding in women presenting with
      excessive menstrual flow. Effective endometrial suppression is the principal
      mechanism underlying both the contraceptive effect and the effect on menstrual
      blood loss. The low release rate oflevonorgestrel results in an absence of
      hormonal side-effects. The unique 'frameless' design characteristics of the
      intrauterine system facilitate insertion and minimize pain and discomfort. These
      factors, together with the low incidence of amenorrhea, appear to be a
      significant step forward from the 'framed' Nova-T levonorgestrel intrauterine
      system (Mirena).

PMID- 11245551
TI  - Patterns of prescription of PC4 by general practitioners in England and Wales.
AB  - OBJECTIVE: To study the pattern of general practitioner prescribing of PC4, the
      most commonly used method of hormonal emergency contraception, in England and
      Wales. METHOD: The UK General Practice Research Database was used to identify,
      from a total population of 4.2 million people on the lists of contributing
      practices, all women aged 10-44 years who were prescribed PC4. Rates of
      prescribing were calculated to produce rates over time by age group, by day of
      week and month of year, and by region. RESULTS: The rate for PC4 prescribing rose
      from about 1.5 per 1,000 women per month in 1992 to about 3.0 in 1995, then
      remained relatively constant until 1998. Rates were highest among 15-19-year-old
      women and next highest among those aged 20-24 years. Rates were higher in Wales
      than in each of the English regions. Excesses of prescribing took place in the
      summer months and between Saturdays and Mondays. CONCLUSION: Reasons for the
      increase in PC4 prescribing rates in the early years of the study are unclear,
      although increasing knowledge of the technique among the population may have
      contributed. There was no evidence of an increase in prescribing following the
      pill scare of October 1995, although there was an increase some months earlier.
      The concentration of requests at weekends suggests the need for weekend access to
      emergency contraception. The summer peak may also indicate a heightened need in
      holiday areas at that time.

PMID- 11245552
TI  - Effect of a desogestrel-containing oral contraceptive on the skin.
AB  - OBJECTIVE: This pilot study evaluated the effects of a desogestrel-containing
      oral contraceptive (DSG-OC) on facial seborrhea (oiliness), acne and related
      factors in otherwise healthy women with moderate facial acne vulgaris. METHODS:
      In this double-blind, placebo-controlled study, 41 women received DSG-OC
      (50/100/150 microg desogestrel plus 35/30/30 microg ethinylestradiol given in a
      7/7/7 day regimen) and 41 received placebo for six cycles. Seborrhea and skin
      assessments, and hormone analyses were performed regularly. RESULTS: Analyses of
      sebum output (measured using Sebutape) indicated that the effect of DSG-OC on the
      skin varied with facial area. Compared with placebo, DSG-OC had a statistically
      significant effect on the cheeks (60% relative reduction in sebum output; p =
      0.02), and a non-significant effect on the forehead (30% relative reduction in
      sebum output). Acne lesion counts did not differ significantly between groups.
      Both patient and investigator assessments of skin condition (visual analog scale)
      indicated significant improvements with DSG-OC compared with placebo. The reduced
      sebum output with DSG-OC is associated with a three-fold increase in sex hormone
      binding globulin, as well as an expected decrease in free testosterone and other
      androgens that were found in this group. CONCLUSION: These results suggest that
      DSG-OC reduces facial oiliness and may be a useful contraceptive choice for women
      with this problem.

PMID- 11245553
TI  - A 1-year pharmacokinetic investigation of a novel oral contraceptive containing
      drospirenone in healthy female volunteers.
AB  - Drospirenone is a novel synthetic progestogen with a pharmacological profile
      similar to that of natural progesterone. It has been developed in combination
      with ethinylestradiol for use as an oral contraceptive (EE/DRSP, Yasmin, Schering
      AG, Berlin, Germany). The pharmacokinetic characteristics of drospirenone and
      ethinylestradiol have been assessed in healthy female volunteers over a 1-year
      period. During each of the 13 treatment cycles, volunteers received the combined
      active ingredients for 21 days, followed by a 7-day, tablet-free interval. The
      concentrations of the serum proteins, sex hormone binding globulin (SHBG) and
      corticoid binding globulin (CBG), were determined at intervals after the
      cessation of treatment (day 21) at the end of cycles 1, 6, 9 and 13. Drospirenone
      and ethinylestradiol were found to be absorbed rapidly and to reach a peak
      concentration in serum 1.5-2.0 h after dosing. Serum concentrations
      ofdrospirenone declined, with mean terminal half-lives of 30.8-32.5 h.
      Accumulation of both drospirenone and ethinylestradiol was observed within a
      treatment cycle, with a mean accumulation ratio of 3.0 for drospirenone and 2.1
      for ethinylestradiol. In addition, serum drospirenone concentrations increased
      between treatment cycles 1 and 6, but remained steady thereafter, as reflected in
      the AUC values determined at the end of treatment cycles 1, 6, 9 and 13. Serum
      SHBG and CBG concentrations declined in a biphasic manner after cessation of
      treatment at the end of cycle 13, and physiological steady-state concentrations
      were reached within 4-6 weeks. In conclusion, drospirenone was absorbed at a
      similar rate as other synthetic progestogens contained in various oral
      contraceptives, as indicated by similar tmax values. The terminal half-life of
      drospirenone was intermediate between those of 19-nortestosterone derivatives
      like desogestrel, levonorgestrel or gestodene and C21-progestogens like
      cyproterone acetate. Both active ingredients of the new contraceptive EE/DRSP
      showed accumulation within a treatment cycle, which is also the case with other
      synthetic progestogen/ethinylestradiol combinations. Similar to other oral
      contraceptives, a reversible induction of serum SHBG and CBG concentrations was
      observed under EE/DRSP treatment.

PMID- 11245554
TI  - The effects of age, body mass index, smoking and general health on the risk of
      venous thromboembolism in users of combined oral contraceptives.
AB  - OBJECTIVES: To investigate the factors associated with idiopathic venous
      thromboembolism in combined oral contraceptive users and to estimate the crude
      and age-specific incidence rates ofidiopathic venous thromboembolism among this
      population. METHODS: The UK MediPlus Database and the General Practice Research
      Database were searched to identify women with evidence of venous thromboembolism
      while exposed to combined oral contraceptives. Cohort and nested case-control
      studies were carried out using the same methodology on both databases. We
      conducted a meta-analysis using the individual data for the cases and controls
      from the two case-control studies to identify factors associated with idiopathic
      venous thromboembolism in women using combined oral contraceptives. RESULTS: The
      incidence rate of idiopathic venous thromboembolism among oral contraceptive
      users was 39.4 per 100,000 exposed woman-years. The age-specific incidence rates
      were found to rise sharply after the age of 39 years. Factors identified as being
      significantly associated with idiopathic venous thromboembolism in women using
      combined oral contraceptives were: body mass index of 25 kg/m2 and over, the
      association rising dramatically in women with a body mass index of 35 kg/m2 or
      more; smoking; general ill health; and asthma. CONCLUSION: We believe that,
      before prescribing combined oral contraceptives, the venous as well as the
      arterial factors need to be considered and, in addition, age, obesity and smoking
      are all relevant when assessing an individual patient's risk.

PMID- 11245556
TI  - Evidence-based family planning: the paradigm for the third millennium.
AB  - Evidence-based medicine applies clinical epidemiology to the care of the
      individual patient. In contrast, autocratic or authoritarian medicine rests
      largely on expert opinion and clinical tradition. The need for evidence-based
      medicine in family planning practice is acute, as counselling for intrauterine
      devices and tubal sterilization attests. Two international evidence-based
      guidelines in family planning, both published in 1996, represent a major advance
      in clinical practice. In addition, the Cochrane Collaboration, a global effort to
      identify and synthesize randomized controlled trials in medicine, now includes
      topics on fertility regulation. Evidence-based clinical guidelines and Cochrane
      systematic reviews are valuable tools for family planning practice. The use of
      evidence-based medicine will improve clinical care today, and, more importantly,
      in the millennium which is just beginning.

PMID- 11245555
TI  - A quantitative biometrological assessment of acne and hormonal evaluation in
      young women using a triphasic low-dose oral contraceptive containing gestodene.
AB  - OBJECTIVE: To investigate the effect of a triphasic low-dose oral contraceptive
      pill containing gestodene on acne severity and hormone levels in young women over
      13 menstrual cycles. METHODS: A total of 33 subjects aged 16-25 years with
      moderate facial acne were enrolled in the study. The primary efficacy end-points
      used in the clinical assessment of acne were the overall severity and number of
      lesions, sebum secretion and superficial follicular biopsy. Both physicians and
      patients evaluated acne status. Blood levels of sex hormone binding globulin
      (SHBG), estradiol, progesterone and androgens were monitored. RESULTS: By cycle
      13, the total lesion count had been reduced by 80%. Physicians and patients
      assessed acne status in 90% and 95% of cases, respectively, as better or much
      better (p < 0.001). At the end of the study, SHBG levels had increased by 229%
      and total and free testosterone levels had decreased by 41% and 70%,
      respectively. CONCLUSION: An oral contraceptive containing triphasic gestodene
      has a beneficial effect on the severity ofacne, decreases major circulating
      androgen levels and is well tolerated.

PMID- 11245557
TI  - Intrauterine contraception in the year 2001: can intrauterine device use be
      revived with new improved contraceptive technology?
AB  - Intrauterine contraception is the most cost-effective reversible method of
      contraception today. The method is becoming increasingly attractive to women due
      to the development of new technologies that not only enhance the performance of
      the intrauterine device (i.e. efficacy is now close to 100%), but also reduce the
      rate of expulsion (in the case of the 'frameless' GyneFix intrauterine device
      (IUD)) and the number of removals for medical reasons. This is important, since
      the demand for intrauterine devices is likely to increase drastically in the
      coming years. The size of the intrauterine foreign body with the mini GyneFix has
      been reduced six-fold since the development of the Lippes Loop, resulting in an
      almost total absence of incompatibility problems. Furthermore, intrauterine
      contraception is entering a new phase with the development of intrauterine
      systems (IUSs) that deliver potent progestins. The Mirena intrauterine system,
      which releases levonorgestrel, has been shown to drastically reduce menstrual
      bleeding. The FibroPlant levonorgestrel IUS has been clinically developed since
      1997 and is a further development of the 'frameless' anchoring IUD concept. The
      majority of women presenting with excessive bleeding can be treated by insertion
      of the IUS, resulting in greatly reduced menstrual blood loss. This is a very
      important result from both a health and a quality-of-life point of view. The fact
      that the IUS is also a potent contraceptive is extremely interesting. We believe,
      therefore, that these new technologies will lead to a re-appraisal of the IUD and
      could revive the use of intrauterine contraception in all parts of the world,
      including those regions where IUD use is presently very low.

PMID- 11245562
TI  - Behcet's disease and interferon: flaws in research integrity of randomized trial.

PMID- 11245558
TI  - Management of liver trauma.

PMID- 11245563
TI  - Is there a gap between preclinical and clinical studies of analgesia?

PMID- 11245564
TI  - Re: proprietary research.

PMID- 11245567
TI  - Superficial femoral vein.

PMID- 11245568
TI  - Embryonic retinoic acid synthesis is essential for heart morphogenesis in the
      mouse.
AB  - Retinoic acid (RA), the active derivative of vitamin A, has been implicated in
      various steps of cardiovascular development, but its contribution to early heart
      morphogenesis has not been clearly established in a mammalian system. To block
      endogenous RA synthesis, we have disrupted the gene encoding RALDH2, the first
      retinaldehyde dehydrogenase whose expression has been detected during early mouse
      post-implantation development. We describe here the heart abnormalities of the RA
      deficient Raldh2 mutants that die in utero at gestational day 10.5. The embryonic
      heart tube forms properly, but fails to undergo rightward looping and, instead,
      forms a medial distended cavity. Expression of early heart determination factors
      is not altered in mutants, and the defect in heart looping does not appear to
      involve the Nodal/Lefty/Pitx2 pathway. Histological and molecular analysis reveal
      distinct anteroposterior components in the mutant heart tube, although posterior
      chamber (atria and sinus venosus) development is severely impaired. Instead of
      forming trabeculae, the developing ventricular myocardium consists of a thick
      layer of loosely attached cells. Ultrastructural analysis shows that most of the
      ventricular wall consists of prematurely differentiated cardiomyocytes, whereas
      undifferentiated cells remain clustered rostrally. We conclude that embryonic RA
      synthesis is required for realization of heart looping, development of posterior
      chambers and proper differentiation of ventricular cardiomyocytes. Nevertheless,
      the precise location of this synthesis may not be crucial, as these defects can
      mostly be rescued by systemic (maternal) RA administration. However, cardiac
      neural crest cells cannot be properly rescued in Raldh2(-/- )embryos, leading to
      outflow tract septation defects.

PMID- 11245569
TI  - Sex determination genes control the development of the Drosophila genital disc,
      modulating the response to Hedgehog, Wingless and Decapentaplegic signals.
AB  - In both sexes, the Drosophila genital disc contains the female and male genital
      primordia. The sex determination gene doublesex controls which of these primordia
      will develop and which will be repressed. In females, the presence of
      Doublesex(F) product results in the development of the female genital primordium
      and repression of the male primordium. In males, the presence of Doublesex(M)
      product results in the development and repression of the male and female genital
      primordia, respectively. This report shows that Doublesex(F) prevents the
      induction of decapentaplegic by Hedgehog in the repressed male primordium of
      female genital discs, whereas Doublesex(M) blocks the Wingless pathway in the
      repressed female primordium of male genital discs. It is also shown that
      Doublesex(F) is continuously required during female larval development to prevent
      activation of decapentaplegic in the repressed male primordium, and during
      pupation for female genital cytodifferentiation. In males, however, it seems that
      Doublesex(M) is not continuously required during larval development for blocking
      the Wingless signaling pathway in the female genital primordium. Furthermore,
      Doublesex(M) does not appear to be needed during pupation for male genital
      cytodifferentiation. Using dachshund as a gene target for Decapentaplegic and
      Wingless signals, it was also found that Doublesex(M) and Doublesex(F) both
      positively and negatively control the response to these signals in male and
      female genitalia, respectively. A model is presented for the dimorphic sexual
      development of the genital primordium in which both Doublesex(M) and Doublesex(F)
      products play positive and negative roles.

PMID- 11245571
TI  - The cephalic neural crest provides pericytes and smooth muscle cells to all blood
      vessels of the face and forebrain.
AB  - Most connective tissues in the head develop from neural crest cells (NCCs), an
      embryonic cell population present only in vertebrates. We show that NCC-derived
      pericytes and smooth muscle cells are distributed in a sharply circumscribed
      sector of the vasculature of the avian embryo. As NCCs detach from the neural
      folds that correspond to the future posterior diencephalon, mesencephalon and
      rhombencephalon, they migrate between the ectoderm and the neuroepithelium into
      the anterior/ventral head, encountering mesoderm-derived endothelial precursors.
      Together, these two cell populations build a vascular tree rooted at the
      departure of the aorta from the heart and ramified into the capillary plexi that
      irrigate the forebrain meninges, retinal choroids and all facial structures,
      before returning to the heart. NCCs ensheath each aortic arch-derived vessel,
      providing every component except the endothelial cells. Within the meninges,
      capillaries with pericytes of diencephalic and mesencephalic neural fold origin
      supply the forebrain, while capillaries with pericytes of mesodermal origin
      supply the rest of the central nervous system, in a mutually exclusive manner.
      The two types of head vasculature contact at a few defined points, including the
      anastomotic vessels of the circle of Willis, immediately ventral to the
      forebrain/midbrain boundary. Over the course of evolution, the vertebrate
      subphylum may have exploited the exceptionally broad range of developmental
      potentialities and the plasticity of NCCs in head remodelling that resulted in
      the growth of the forebrain.

PMID- 11245570
TI  - TGF beta 2, LIF and FGF2 cooperate to induce nephrogenesis.
AB  - The metanephric kidney develops from interactions between the epithelial ureteric
      bud and adjacent metanephric mesenchyme, which is induced by the bud to form the
      epithelia of the nephron. We have found that leukemia inhibitory factor (LIF) and
      transforming growth factor beta 2 (TGF beta 2) are secreted by inductive rat bud
      cells and cooperate to enhance and accelerate renal tubule formation in uninduced
      rat metanephric mesenchymal explants. LIF alone or TGF beta 2 with fibroblast
      growth factor 2 induced numerous tubules in isolated mesenchymes over an 8 day
      period, while (in combination) all three caused abundant tubule formation in 72
      hours. Furthermore, neutralization of Wnt ligands with antagonist-secreted
      Frizzled-related protein 1 abrogated these responses and combinatorial
      cytokine/growth factor stimulation of explants augmented nuclear activation of
      Tcf1/Lef1, suggesting that LIF and TGF beta 2/FGF2 cooperate to regulate
      nephrogenesis through a common Wnt-dependent mechanism.

PMID- 11245572
TI  - A single histone H1 isoform (H1.1) is essential for chromatin silencing and
      germline development in Caenorhabditis elegans.
AB  - In remarkable contrast to somatic cells, the germline of the nematode
      Caenorhabditis elegans efficiently silences transgenic DNA. The molecular
      mechanisms responsible for this have been shown to implicate chromatin proteins
      encoded by the mes genes (Kelly, W. G. and Fire, A. (1998) Development 125, 2451
      2456), of which two are the C. elegans homologs of Polycomb Group gene
      transcriptional repressors. We have analyzed the contribution of the histone H1
      gene family to this specific aspect of germ cells in C. elegans. We show with
      isotype-specific double stranded RNA-mediated interference (RNAi) that a single
      member of this gene family (H1.1) is essential for the repression of a silenced
      reporter-transgene in the germline of hermaphrodites and males, whereas no change
      is found in the somatic expression of this reporter. Additionally, RNA-mediated
      interference with H1.1 gene expression can cause a phenotype with severe
      affection of germline proliferation and differentiation in the hermaphrodite, and
      even sterility (5%-11% penetrance). These and further features observed in
      histone H1.1 RNAi experiments are also characteristic of the mes phenotype
      (Garvin, C., Holdeman, R. and Strome, S. (1998) Genetics 148, 167-185), which is
      believed to result from the desilencing of genes required for somatic
      differentiation in the germline. Our observations therefore support this
      interpretation of the mes phenotype and they identify a single histone H1 isoform
      (H1.1) as a new component specifically involved in chromatin silencing in the
      germline of C. elegans.

PMID- 11245573
TI  - Inducible nuclear translocation of a STAT protein in Dictyostelium prespore
      cells: implications for morphogenesis and cell-type regulation.
AB  - Dd-STATa, the Dictyostelium STAT (signal transducer and activator of
      transcription) protein, is selectively localised in the nuclei of a small subset
      of prestalk cells located in the slug tip. Injection of cAMP into the
      extracellular spaces in the rear of the slug induces rapid nuclear translocation
      of a Dd-GFP:STATa fusion protein in prespore cells surrounding the site of
      injection. This suggests that cAMP signals that emanate from the tip direct the
      localised nuclear accumulation of Dd-STATa. It also shows that prespore cells are
      competent to respond to cAMP, by Dd-STATa activation, and it implies that cAMP
      signalling is in some way limiting in the rear of the slug. Co-injection of a
      specific inhibitor of the cAR1 serpentine cAMP receptor almost completely
      prevents the cAMP-induced nuclear translocation, showing that most or all of the
      cAMP signal is transduced by cAR1. Dd-GFP:STATa also rapidly translocates into
      the nuclei of cells adjoining the front and back cut edges when a slug is
      bisected. Less severe mechanical disturbances, such as pricking the rear of a
      slug with an unfilled micropipette, also cause a more limited nuclear
      translocation of Dd-GFP:STATa. We propose that these signalling events form part
      of a repair mechanism that is activated when the migrating slug suffers
      mechanical damage.

PMID- 11245574
TI  - SPATULA, a gene that controls development of carpel margin tissues in
      Arabidopsis, encodes a bHLH protein.
AB  - Studies involving mutants of the gene SPATULA indicate that it promotes the
      growth of carpel margins and of pollen tract tissues derived from them. We show
      that it encodes a new member of the basic-helix-loop-helix family of
      transcription factors. SPATULA is expressed in marginal and pollen tract tissues
      throughout their development confirming its role in regulating their growth. It
      is also expressed in many other tissues where it may act redundantly to control
      growth, including the peripheral zone of the shoot apical meristem, and specific
      tissues within leaves, petals, stamens and roots. Expression in the stomium,
      funiculus and valve dehiscence zone indicates an additional role in abscission.
      SPATULA expression does not require the function of the other carpel development
      genes CRABS CLAW and AGAMOUS, although its expression is repressed in first whorl
      organs by the A function gene APETALA2. Further, we have shown that disruptions
      to gynoecial pattern formation seen in ettin mutants can largely be attributed to
      ectopic SPATULA action. ETTIN's role seems to be to negatively regulate SPATULA
      expression in abaxial regions of the developing gynoecium. SPATULA is the first
      basic-helix-loop-helix gene in plants known to play a role in floral
      organogenesis.

PMID- 11245575
TI  - An instructive function for Notch in promoting gliogenesis in the zebrafish
      retina.
AB  - The Gal4-UAS technique has been used to misexpress a constitutively active Notch
      receptor variant (notch1a-intra) in the developing zebrafish retina. This is the
      first study to use this technique to misexpress genes and assess their function
      in neural development of the zebrafish. Expression of activated Notch1a either
      ubiquitously, driven by a heat-shock70 promoter, or in a spatially regulated
      manner, controlled by the deltaD promoter, causes a block in neuronal
      differentiation that affects all cell types. Developing cells take on either a
      glial fate or remain undifferentiated. A large number of cells eventually undergo
      apoptosis. These phenotypic effects of activated Notch1a are expressed cell
      autonomously. Cells within central regions of the retina adopt a glial fate if
      they express activated Notch1a in a time window that extends from 27 to 48 hours
      postfertilization. This period corresponds mainly to the time of origin of
      ganglion cells in the normal retina. Activation of notch1a at later stages
      results in defects in cell type specification that remain restricted to the
      ciliary marginal zone, whereas neuronal types are specified normally within the
      central region. These observations indicate that glial differentiation is
      initiated by Notch1a-intra expressing cells, which become postmitotic in the same
      time window. Our results strongly suggest that Notch1a instructs a certain cell
      population to enter gliogenesis, and keeps the remaining cells in an
      undifferentiated state. Some or all of these cells will eventually succumb to
      apoptosis.

PMID- 11245576
TI  - Establishment and maintenance of parasegmental compartments.
AB  - Embryos of higher metazoans are divided into repeating units early in
      development. In Drosophila, the earliest segmental units to form are the
      parasegments. Parasegments are initially defined by alternating stripes of
      expression of the fushi-tarazu and even-skipped genes. How fushi-tarazu and even
      skipped define the parasegment boundaries, and how parasegments are lost when
      fushi-tarazu or even-skipped fail to function correctly, have never been fully or
      properly explained. Here we show that parasegment widths are defined early by the
      relative levels of fushi-tarazu and even-skipped at stripe junctions. Changing
      these levels results in alternating wide and narrow parasegments. When shifted by
      30% or more, the enlarged parasegments remain enlarged and the reduced
      parasegments are lost. Loss of the reduced parasegments occurs in three steps;
      delamination of cells from the epithelial layer, apoptosis of the delaminated
      cells and finally apoptosis of inappropriate cells remaining at the surface. The
      establishment and maintenance of vertebrate metameres may be governed by similar
      processes and properties.

PMID- 11245577
TI  - Defective zonae pellucidae in Zp2-null mice disrupt folliculogenesis, fertility
      and development.
AB  - All vertebrate eggs are surrounded by an extracellular matrix. This matrix is
      known as the zona pellucida in mammals and is critically important for the
      survival of growing oocytes, successful fertilization and the passage of early
      embryos through the oviduct. The mouse zona pellucida is composed of three
      glycoproteins (ZP1, ZP2 and ZP3), each encoded by a single copy gene. Using
      targeted mutagenesis in embryonic stem cells, Zp2-null mouse lines have been
      established. ZP1 and ZP3 proteins continue to be synthesized and form a thin zona
      matrix in early follicles that is not sustained in pre-ovulatory follicles. The
      abnormal zona matrix does not affect initial folliculogenesis, but there is a
      significant decrease in the number of antral stage follicles in ovaries isolated
      from mice lacking a zona pellucida. Few eggs are detected in the oviduct after
      stimulation with gonadotropins, and no two-cell embryos are recovered after
      mating Zp2-null females with normal male mice. The structural defect is more
      severe than that observed in Zp1-null mice, which have decreased fecundity, but
      not quite as severe as that observed in Zp3-null mice, which never form a visible
      zona pellucida and are sterile. Although zona-free oocytes matured and fertilized
      in vitro can progress to the blastocyst stage, the developmental potential of
      blastocysts derived from either Zp2- or Zp3-null eggs appears compromised and,
      after transfer to foster mothers, live births have not been observed. Thus, in
      addition to its role in fertilization and protection of early embryos, these data
      are consistent with the zona pellucida maintaining interactions between granulosa
      cells and oocytes during folliculogenesis that are critical to maximize
      developmental competence of oocytes.

PMID- 11245578
TI  - The CUP-SHAPED COTYLEDON1 gene of Arabidopsis regulates shoot apical meristem
      formation.
AB  - In higher plants, molecular mechanisms regulating shoot apical meristem (SAM)
      formation and organ separation are largely unknown. The CUC1 (CUP-SHAPED
      COTYLEDON1) and CUC2 are functionally redundant genes that are involved in these
      processes. We cloned the CUC1 gene by a map-based approach, and found that it
      encodes a NAC-domain protein highly homologous to CUC2. CUC1 mRNA was detected in
      the presumptive SAM during embryogenesis, and at the boundaries between floral
      organ primordia. Surprisingly, overexpression of CUC1 was sufficient to induce
      adventitious shoots on the adaxial surface of cotyledons. Expression analyses in
      the overexpressor and in loss-of-function mutants suggest that CUC1 acts upstream
      of the SHOOT MERISTEMLESS gene.

PMID- 11245579
TI  - The role of centrosomes and astral microtubules during asymmetric division of
      Drosophila neuroblasts.
AB  - Drosophila neuroblasts are stem cells that divide asymmetrically to produce
      another large neuroblast and a smaller ganglion mother cell (GMC). During
      neuroblast division, several cell fate determinants, such as Miranda, Prospero
      and Numb, are preferentially segregated into the GMC, ensuring its correct
      developmental fate. The accurate segregation of these determinants relies on
      proper orientation of the mitotic spindle within the dividing neuroblast, and on
      the correct positioning of the cleavage plane. In this study we have analyzed the
      role of centrosomes and astral microtubules in neuroblast spindle orientation and
      cytokinesis. We examined neuroblast division in asterless (asl) mutants, which,
      although devoid of functional centrosomes and astral microtubules, form well
      focused anastral spindles that undergo anaphase and telophase. We show that asl
      neuroblasts assemble a normal cytokinetic ring around the central spindle midzone
      and undergo unequal cytokinesis. Thus, astral microtubules are not required for
      either signaling or positioning cytokinesis in Drosophila neuroblasts. Our
      results indicate that the cleavage plane is dictated by the positioning of the
      central spindle midzone within the cell, and suggest a model on how the central
      spindle attains an asymmetric position during neuroblast mitosis. We have also
      analyzed the localization of Miranda during mitotic division of asl neuroblasts.
      This protein accumulates in morphologically regular cortical crescents but these
      crescents are mislocalized with respect to the spindle orientation. This suggests
      that astral microtubules mediate proper spindle rotation during neuroblast
      division.

PMID- 11245580
TI  - mKlf7, a potential transcriptional regulator of TrkA nerve growth factor receptor
      expression in sensory and sympathetic neurons.
AB  - Development of the nervous system relies on stringent regulation of genes that
      are crucial to this process. TrkA, the receptor for nerve growth factor (NGF), is
      tightly regulated during embryonic development and is essential for the survival
      and differentiation of neural crest-derived sensory and sympathetic neurons. We
      have previously identified a mouse TrkA enhancer and have characterized several
      cis regulatory elements that are important for appropriate TrkA expression in
      vivo. We now report the cloning of a novel gene encoding a Kruppel-like factor
      from a mouse dorsal root ganglion expression library. This Kruppel-like factor,
      named mKlf7, binds specifically to an Ikaros core binding element that is crucial
      for in vivo TrkA enhancer function. Using in situ hybridization, we demonstrate
      that mKlf7 is coexpressed with TrkA in sensory and sympathetic neurons during
      embryogenesis and in adulthood. These data are consistent with the idea that
      mKlf7 may directly regulate TrkA gene expression in the peripheral nervous
      system.

PMID- 11245581
TI  - An autoregulatory feedback loop directs the localized expression of the
      Drosophila CPEB protein Orb in the developing oocyte.
AB  - The RRM-type RNA binding protein Orb plays a central role in the establishment of
      polarity in the Drosophila egg and embryo. In addition to its role in the
      formation and initial differentiation of the egg chamber, orb is required later
      in oogenesis for the determination of the dorsoventral (DV) and anteroposterior
      (AP) axes. In DV axis formation, Orb protein is required to localize and
      translate gurken mRNA at the dorsoanterior part of the oocyte. In AP axis
      formation, Orb is required for the translation of oskar mRNA. In each case, Orb
      protein is already localized at the appropriate sites within the oocyte before
      the arrival of the mRNAs encoding axis determinants. We present evidence that an
      autoregulatory mechanism is responsible for directing the on site accumulation of
      Orb protein in the Drosophila oocyte. This orb autoregulatory activity ensures
      the accumulation of high levels of Orb protein at sites in the oocyte that
      contain localized orb message.

PMID- 11245582
TI  - Specification of left-right asymmetry in the embryonic gut of Drosophila.
AB  - Most animals exhibit stable left-right asymmetries in their body. Although
      significant progress has been made in elucidating the mechanisms that set up
      these asymmetries in vertebrates, nothing is known about them in Drosophila. This
      is usually attributed to the fact that no reversals of stable left-right
      asymmetries have been observed in Drosophila, although relevant surveys have been
      carried out. We have focused on the asymmetry of the proventriculus in the
      embryonic gut of Drosophila, an aspect of left-right asymmetry that is extremely
      stable in wild-type flies. We show that this asymmetry can be reversed by
      mutations in the dicephalic and wunen genes, which also cause reversals in the
      antero-posterior axis of the embryo relative to its mother. This is the first
      observation to suggest that left-right asymmetries in Drosophila can be reversed
      by genetic/developmental manipulations. It also suggests that maternal signals
      may initiate the specification of some left-right asymmetries in the embryo.

PMID- 11245583
TI  - GAP-43 promoter elements in transgenic zebrafish reveal a difference in signals
      for axon growth during CNS development and regeneration.
AB  - A pivotal event in neural development is the point at which differentiating
      neurons become competent to extend long axons. Initiation of axon growth is
      equally critical for regeneration. Yet we have a limited understanding of the
      signaling pathways that regulate the capacity for axon growth during either
      development or regeneration. Expression of a number of genes encoding growth
      associated proteins (GAPs) accompanies both developmental and regenerative axon
      growth and has led to the suggestion that the same signaling pathways regulate
      both modes of axon growth. We have tested this possibility by asking whether a
      promoter fragment from a well characterized GAP gene, GAP-43, is sufficient to
      activate expression in both developing and regenerating neurons. We generated
      stable lines of transgenic zebrafish that express green fluorescent protein (GFP)
      under regulation of a 1 kb fragment of the rat GAP-43 gene, a fragment that
      contains a number of evolutionarily conserved elements. Analysis of GFP
      expression in these lines confirms that the rat 1 kb region can direct growth
      associated expression of the transgene in differentiating neurons that extend
      long axons. Furthermore, this region supports developmental down-regulation of
      transgene expression which, like the endogenous gene, coincides with neuronal
      maturation. Strikingly, these same sequences are insufficient for directing
      expression in regenerating neurons. This finding suggests that signaling pathways
      regulating axon growth during development and regeneration are not the same.
      While these results do not exclude the possibility that pathways involved in
      developmental axon growth are also active in regenerative growth, they do
      indicate that signaling pathway(s) controlling activation of the GAP-43 gene
      after CNS injury differ in at least one key component from the signals
      controlling essential features of developmental axon growth.

PMID- 11245584
TI  - Role of the EGFR/Ras/Raf pathway in specification of photoreceptor cells in the
      Drosophila retina.
AB  - The Drosophila EGF receptor is required for differentiation of many cell types
      during eye development. We have used mosaic analysis with definitive null
      mutations to analyze the effects of complete absence of EGFR, Ras or Raf proteins
      during eye development. The Egfr, ras and raf genes are each found to be
      essential for recruitment of R1-R7 cells. In addition Egfr is autonomously
      required for MAP kinase activation. EGFR is not essential for R8 cell
      specification, either alone or redundantly with any other receptor that acts
      through Ras or Raf, or by activating MAP kinase. As with Egfr, loss of ras or raf
      perturbs the spacing and arrangement of R8 precursor cells. R8 cell spacing is
      not affected by loss of argos in posteriorly juxtaposed cells, which rules out a
      model in which EGFR acts through argos expression to position R8 specification in
      register between adjacent columns of ommatidia. The R8 spacing role of the EGFR
      was partially affected by simultaneous deletion of spitz and vein, two ligand
      genes, but the data suggest that EGFR activation independent of spitz and vein is
      also involved. The results prove that R8 photoreceptors are specified and
      positioned by distinct mechanisms from photoreceptors R1-R7.

PMID- 11245585
TI  - serpent, a GATA-like transcription factor gene, induces fat-cell development in
      Drosophila melanogaster.
AB  - The GATA-like transcription factor gene serpent is necessary for embryonic fat
      cell differentiation in Drosophila (Sam, S., Leise, W. and Hoshizaki, D. K.
      (1996) Mech. Dev. 60, 197-205) and has been proposed to function in a cell-fate
      choice between fat cell and somatic gonadal precursors (Moore, L. A., Broihier,
      H. T., Van Doren, M. and Lehmann, R. (1998) Development 125, 837-44; Riechmann,
      V., Irion, U., Wilson, R., Grosskortenhaus, R. and Leptin, M. (1997) Development
      124, 2915-22). Here, we report that deregulated expression of serpent in the
      mesoderm induces the formation of ectopic fat cells and prevents the migration
      and coalescence of the somatic gonadal precursors. The ectopic fat cells do not
      arise from hyperproliferation of the primary fat-cell clusters but they do
      associate with the endogenous fat cells to form a fat body that is expanded in
      both the dorsal/ventral and anterior/posterior axes. Misexpression of serpent
      also affects the differentiation of muscle cells. Few body-wall muscle precursors
      are specified and there is a loss of most body-wall muscle fibers. The precursors
      of the visceral mesoderm are also absent and concomitantly the visceral muscle is
      absent. We suggest that the ectopic fat cells might originate from cells that
      have the potential, but do not normally, differentiate into fat cells or from
      cells that have acquired a fat-cell fate. In light of our results, we discuss the
      role of serpent in fat-cell specification and in cell fate choices.

PMID- 11245586
TI  - PAR-1 is required for the maintenance of oocyte fate in Drosophila.
AB  - The PAR-1 kinase is required for the posterior localisation of the germline
      determinants in C. elegans and Drosophila, and localises to the posterior of the
      zygote and the oocyte in each case. We show that Drosophila PAR-1 is also
      required much earlier in oogenesis for the selection of one cell in a germline
      cyst to become the oocyte. Although the initial steps in oocyte determination are
      delayed, three markers for oocyte identity, the synaptonemal complex, the
      centrosomes and Orb protein, still become restricted to one cell in mutant
      clones. However, the centrosomes and Orb protein fail to translocate from the
      anterior to the posterior cortex of the presumptive oocyte in region 3 of the
      germarium, and the cell exits meiosis and becomes a nurse cell. Furthermore,
      markers for the minus ends of the microtubules also fail to move from the
      anterior to the posterior of the oocyte in mutant clones. Thus, PAR-1 is required
      for the maintenance of oocyte identity, and plays a role in microtubule-dependent
      localisation within the oocyte at two stages of oogenesis. Finally, we show that
      PAR-1 localises on the fusome, and provides a link between the asymmetry of the
      fusome and the selection of the oocyte.

PMID- 11245587
TI  - Specification of ectodermal teloblast lineages in embryos of the oligochaete
      annelid Tubifex: involvement of novel cell-cell interactions.
AB  - In embryos of clitellate annelids (i.e. oligochaetes and leeches), four
      ectodermal teloblasts (ectoteloblasts N, O, P and Q) are generated on either side
      through a stereotyped sequence of cell divisions of a proteloblast, NOPQ. The
      four ectoteloblasts assume distinct fates and produce bandlets of smaller progeny
      cells, which join together to form an ectodermal germ band. The pattern of the
      germ band, with respect to the ventrodorsal order of the bandlets, has been
      highly preserved in clitellate annelids. We show that specification of
      ectoteloblast lineages in the oligochaete annelid Tubifex involves cell
      interaction networks distinct from those in leeches. Cell ablation experiments
      have shown that fates of teloblasts N, P and Q in Tubifex embryos are determined
      rigidly as early as their birth. In contrast, the O teloblast and its progeny are
      initially pluripotent and their fate becomes restricted to the O fate through an
      inductive signal emanating from the P lineage. In the absence of this signal, the
      O lineage assumes the P fate. These results differ significantly from those
      obtained in embryos of the leech Helobdella, suggesting the diversity of
      patterning mechanisms that give rise to germ bands with similar morphological
      pattern.

PMID- 11245588
TI  - Oxidant stress and endothelial cell dysfunction.
AB  - Reactive oxygen species (ROS) are generated at sites of inflammation and injury,
      and at low levels, ROS can function as signaling molecules participating as
      signaling intermediates in regulation of fundamental cell activities such as cell
      growth and cell adaptation responses, whereas at higher concentrations, ROS can
      cause cellular injury and death. The vascular endothelium, which regulates the
      passage of macromolecules and circulating cells from blood to tissues, is a major
      target of oxidant stress, playing a critical role in the pathophysiology of
      several vascular diseases and disorders. Specifically, oxidant stress increases
      vascular endothelial permeability and promotes leukocyte adhesion, which are
      coupled with alterations in endothelial signal transduction and redox-regulated
      transcription factors such as activator protein-1 and nuclear factor-kappaB. This
      review discusses recent findings on the cellular and molecular mechanisms by
      which ROS signal events leading to impairment of endothelial barrier function and
      promotion of leukocyte adhesion. Particular emphasis is placed on the regulation
      of cell-cell and cell-surface adhesion molecules, the actin cytoskeleton, key
      protein kinases, and signal transduction events.

PMID- 11245589
TI  - Bitter taste transduced by PLC-beta(2)-dependent rise in IP(3) and alpha
      gustducin-dependent fall in cyclic nucleotides.
AB  - Current evidence points to the existence of multiple processes for bitter taste
      transduction. Previous work demonstrated involvement of the polyphosphoinositide
      system and an alpha-gustducin (Galpha(gust))-mediated stimulation of
      phosphodiesterase in bitter taste transduction. Additionally, a taste-enriched G
      protein gamma-subunit, Ggamma(13), colocalizes with Galpha(gust) and mediates the
      denatonium-stimulated production of inositol 1,4,5-trisphosphate (IP(3)). Using
      quench-flow techniques, we show here that the bitter stimuli, denatonium and
      strychnine, induce rapid (50-100 ms) and transient reductions in cAMP and cGMP
      and increases in IP(3) in murine taste tissue. This decrease of cyclic
      nucleotides is inhibited by Galpha(gust) antibodies, whereas the increase in
      IP(3) is not affected by antibodies to Galpha(gust). IP(3) production is
      inhibited by antibodies specific to phospholipase C-beta(2) (PLC-beta(2)), a PLC
      isoform known to be activated by Gbetagamma-subunits. Antibodies to PLC-beta(3)
      or to PLC-beta(4) were without effect. These data suggest a transduction
      mechanism for bitter taste involving the rapid and transient metabolism of dual
      second messenger systems, both mediated through a taste cell G protein, likely
      composed of Galpha(gust)/beta/gamma(13), with both systems being simultaneously
      activated in the same bitter-sensitive taste receptor cell.

PMID- 11245590
TI  - cAMP-sensitive endocytic trafficking in A6 epithelia.
AB  - Blocker-induced noise analysis and laser scanning confocal microscopy were used
      to test the idea that cAMP-mediated vesicle exocytosis/endocytosis may be a
      mechanism for regulation of functional epithelial Na+ channels (ENaCs) at apical
      membranes of A6 epithelia. After forskolin stimulation of Na+ transport and
      labeling apical membranes with the fluorescent dye N-(3-triethylammoniumpropyl)4
      (6-4 diethylaminophenyl) hexatrienyl pyridinium dibromide (FM 4-64), ENaC
      densities (N(T)) decreased exponentially (time constant approximately 20 min)
      from mean values of 320 to 98 channels/cell within 55 min during washout of
      forskolin. Two populations of apical membrane-labeled vesicles appeared in the
      cytosol within 55 min, reaching mean values near 18 vesicles/cell, compared with
      five vesicles per cell in control, unstimulated tissues. The majority of cAMP
      dependent endocytosed vesicles remained within a few micrometers of the apical
      membranes for the duration of the experiments. A minority of vesicles migrated to
      >5 microm below the apical membrane. Because steady states require identical
      rates of endocytosis and exocytosis, and because forskolin increased endocytic
      rates by fivefold or more, cAMP/protein kinase A acts kinetically not only to
      increase rates of cycling of vesicles at the apical membranes, but also
      principally to increase exocytic rates. These observations are consistent with
      and support, but do not prove, that vesicle trafficking is a mechanism for cAMP
      mediated regulation of apical membrane channel densities in A6 epithelia.

PMID- 11245591
TI  - Differential global gene expression in red and white skeletal muscle.
AB  - The differences in gene expression among the fiber types of skeletal muscle have
      long fascinated scientists, but for the most part, previous experiments have only
      reported differences of one or two genes at a time. The evolving technology of
      global mRNA expression analysis was employed to determine the potential
      differential expression of approximately 3,000 mRNAs between the white quad
      (white muscle) and the red soleus muscle (mixed red muscle) of female ICR mice
      (30-35 g). Microarray analysis identified 49 mRNA sequences that were
      differentially expressed between white and mixed red skeletal muscle, including
      newly identified differential expressions between muscle types. For example, the
      current findings increase the number of known, differentially expressed mRNAs for
      transcription factors/coregulators by nine and signaling proteins by three. The
      expanding knowledge of the diversity of mRNA expression between white and mixed
      red muscle suggests that there could be quite a complex regulation of phenotype
      between muscles of different fiber types.

PMID- 11245592
TI  - Circulating monocytes are not the source of elevations in plasma IL-6 and TNF
      alpha levels after prolonged running.
AB  - The present study was undertaken to examine the effect of prolonged running on
      monocyte intracellular cytokine production and plasma cytokine concentration.
      Blood samples were collected 1 h before, immediately after, 2 h after, and 24 h
      after a competitive marathon run. There was no change in the number of cells
      spontaneously producing tumor necrosis factor (TNF)-alpha; however, there was a
      decrease in the number of cells producing interleukin (IL)-1alpha and IL-6 (P <
      0.01) postexercise. In contrast, there was an increase in the number of monocytes
      that responded to lipopolysaccharide stimulation by producing IL-1alpha, TNF
      alpha, and IL-6 (P < 0.01) immediately and 2 h postexercise; however, these cells
      contained less cytokine (P < 0.05). Plasma IL-6, TNF-alpha, epinephrine,
      norepinephrine, and cortisol concentrations were markedly increased (P < 0.01)
      postexercise. These data demonstrate that circulating monocytes are not the
      source of elevated levels of plasma IL-6 and TNF-alpha after prolonged running.
      In addition, it is likely that stress hormones result in a decrease in the amount
      of cytokine produced by LPS-stimulated cells postexercise.

PMID- 11245593
TI  - Role of SNAP-23 in trafficking of H+-ATPase in cultured inner medullary
      collecting duct cells.
AB  - The trafficking of H+-ATPase vesicles to the apical membrane of inner medullary
      collecting duct (IMCD) cells utilizes a mechanism similar to that described in
      neurosecretory cells involving soluble N-ethylmaleimide-sensitive factor
      attachment protein target receptor (SNARE) proteins. Regulated exocytosis of
      these vesicles is associated with the formation of SNARE complexes. Clostridial
      neurotoxins that specifically cleave the target (t-) SNARE, syntaxin-1, or the
      vesicle SNARE, vesicle-associated membrane protein-2, reduce SNARE complex
      formation, H+-ATPase translocation to the apical membrane, and inhibit H+
      secretion. The purpose of these experiments was to characterize the physiological
      role of a second t-SNARE, soluble N-ethylmaleimide-sensitive factor attachment
      protein (SNAP)-23, a homologue of the neuronal SNAP-25, in regulated exocytosis
      of H+-ATPase vesicles. Our experiments document that 25-50 nM botulinum toxin
      (Bot) A or E cleaves rat SNAP-23 and thereby reduces immunodetectable and (35)S
      labeled SNAP-23 by >60% within 60 min. Addition of 25 nM BotE to IMCD homogenates
      reduces the amount of the 20 S-like SNARE complex that can be immunoprecipitated
      from the homogenate. Treatment of intact IMCD monolayers with BotE reduces the
      amount of H+-ATPase translocated to the apical membrane by 52 +/- 2% of control
      and reduces the rate of H+ secretion by 77 +/- 3% after acute cell acidification.
      We conclude that SNAP-23 is a substrate for botulinum toxin proteolysis and has a
      critical role in the regulation of H+-ATPase exocytosis and H+ secretion in these
      renal epithelial cells.

PMID- 11245594
TI  - Effects of aging on actin sliding speed on myosin from single skeletal muscle
      cells of mice, rats, and humans.
AB  - The effects of aging on the mechanical properties of myosin were measured in 87
      fibers from muscles of humans (n = 40), rats (n = 21), and mice (n = 26) using a
      single fiber in vitro motility assay. Irrespective of species, an 18-25% aging
      related slowing in the speed of actin filaments was observed from 62 single
      fibers expressing the slow (type I) beta-myosin heavy chain isoform. The
      mechanisms underlying the aging-related slowing of motility speed remain unknown,
      but it is suggested that posttranslational modifications of myosin by oxidative
      stress, glycation, or nitration play an important role. The aging-related slowing
      in the speed of actin filaments propelled by the type I myosin was confirmed in
      three mammalian species with an approximately 3,400-fold difference in body size.
      Motility speed from human myosin was 3-fold slower than from myosin of the
      approximately 3,400-fold smaller mouse and approximately twofold slower when
      compared with the approximately 130-fold smaller rat, irrespective of age. A
      strong correlation was observed between the log values of actin sliding speed and
      body mass, suggesting that the effects of scaling is, at least in part, due to
      altered functional properties of the motor protein itself.

PMID- 11245595
TI  - PLD pathway involved in carbachol-induced Cl- secretion: possible role of TNF
      alpha.
AB  - In a previous study, it was found that exposure to tumor necrosis factor-alpha
      (TNF-alpha) potentiated the electrophysiological response to carbachol in a time
      dependent and cycloheximide-sensitive manner. It was deduced that the
      potentiation could be due to protein kinase C activity because of increased 1,2
      diacylglycerol. It was also observed that propranolol could decrease the
      electrophysiological response to carbachol (Oprins JC, Meijer HP, and Groot JA.
      Am J Physiol Cell Physiol 278: C463-C472, 2000). The aim of the present study was
      to investigate whether the phospholipase D (PLD) pathway plays a role in the
      carbachol response and the potentiating effect of TNF-alpha. The
      transphosphatidylation reaction in the presence of the primary alcohol 1-butanol
      [leading to stable phosphatidylbutanol (Pbut) formation] was used to measure
      activity of PLD. The phosphatidic acid (PA) levels were also measured. Muscarinic
      stimulation resulted in an increased formation of Pbut and PA. TNF-alpha
      decreased levels of PA.

PMID- 11245596
TI  - K+ channels and the microglial respiratory burst.
AB  - Microglial activation following central nervous system damage or disease often
      culminates in a respiratory burst that is necessary for antimicrobial function,
      but, paradoxically, can damage bystander cells. We show that several K+ channels
      are expressed and play a role in the respiratory burst of cultured rat microglia.
      Three pharmacologically separable K+ currents had properties of Kv1.3 and the
      Ca2+/calmodulin-gated channels, SK2, SK3, and SK4. mRNA was detected for Kv1.3,
      Kv1.5, SK2, and/or SK3, and SK4. Protein was detected for Kv1.3, Kv1.5, and SK3
      (selective SK2 and SK4 antibodies not available). No Kv1.5-like current was
      detected, and confocal immunofluorescence showed the protein to be subcellular,
      in contrast to the robust membrane localization of Kv1.3. To determine whether
      any of these channels play a role in microglial activation, a respiratory burst
      was stimulated with phorbol 12-myristate 13-acetate and measured using a single
      cell, fluorescence-based dihydrorhodamine 123 assay. The respiratory burst was
      markedly inhibited by blockers of SK2 (apamin) and SK4 channels (clotrimazole and
      charybdotoxin), and to a lesser extent, by the potent Kv1.3 blocker agitoxin-2.

PMID- 11245597
TI  - Differential effects of flavonoids on 3T3-L1 adipogenesis and lipolysis.
AB  - Flavonoids, polyphenolic compounds that exist widely in plants, inhibit cell
      proliferation and increase cell differentiation in many cancerous and
      noncancerous cell lines. Because terminal differentiation of preadipocytes to
      adipocytes depends on proliferation of both pre- and postconfluent preadipocytes,
      we predicted that flavonoids would inhibit adipogenesis in the 3T3-L1
      preadipocyte cell line. The flavonoids genistein and naringenin inhibited
      proliferation of preconfluent preadipocytes in a time- and dose-dependent manner.
      When added to 2-day postconfluent preadipocytes at the induction of
      differentiation, genistein inhibited mitotic clonal expansion, triglyceride
      accumulation, and peroxisome proliferator-activated receptor-gamma expression,
      but naringenin had no effect. The antiadipogenic effect of genistein was not due
      to inhibition of insulin receptor subtrate-1 tyrosine phosphorylation. When added
      3 days after induction of differentiation, neither flavonoid inhibited
      differentiation. In fully differentiated adipocytes, genistein increased basal
      and epinephrine-induced lipolysis, but naringenin had no significant effects.
      These data demonstrate that genistein and naringenin, despite structural
      similarity, have differential effects on adipogenesis and adipocyte lipid
      metabolism.

PMID- 11245598
TI  - Human neutrophils facilitate tumor cell transendothelial migration.
AB  - Tumor cell extravasation plays a key role in tumor metastasis. However, the
      precise mechanisms by which tumor cells migrate through normal vascular
      endothelium remain unclear. In this study, using an in vitro transendothelial
      migration model, we show that human polymorphonuclear neutrophils (PMN) assist
      the human breast tumor cell line MDA-MB-231 to cross the endothelial barrier. We
      found that tumor-conditioned medium (TCM) downregulated PMN cytocidal function,
      delayed PMN apoptosis, and concomitantly upregulated PMN adhesion molecule
      expression. These PMN treated with TCM attached to tumor cells and facilitated
      tumor cell migration through different endothelial monolayers. In contrast, MDA
      MB-231 cells alone did not transmigrate. FACScan analysis revealed that these
      tumor cells expressed high levels of intercellular adhesion molecule-1 (ICAM-1)
      but did not express CD11a, CD11b, or CD18. Blockage of CD11b and CD18 on PMN and
      of ICAM-1 on MDA-MB-231 cells significantly attenuated TCM-treated, PMN-mediated
      tumor cell migration. These tumor cells still possessed the ability to
      proliferate after PMN-assisted transmigration. These results indicate that TCM
      treated PMN may serve as a carrier to assist tumor cell transendothelial
      migration and suggest that tumor cells can exploit PMN and alter their function
      to facilitate their extravasation.

PMID- 11245599
TI  - Caveolin-1 expression sensitizes fibroblastic and epithelial cells to apoptotic
      stimulation.
AB  - The potential role of caveolin-1 in apoptosis remains controversial. Here, we
      investigate whether caveolin-1 expression is proapoptotic or antiapoptotic using
      a well-defined antisense approach. We show that NIH/3T3 cells harboring antisense
      caveolin-1 are resistant to staurosporine-induced apoptosis, as assessed using
      cell morphology, DNA content, caspase 3 activation, and focal adhesion kinase
      cleavage. Importantly, sensitivity to apoptosis is recovered when caveolin-1
      levels are restored. Conversely, recombinant stable expression of caveolin-1 in
      T24 bladder carcinoma cells sensitizes these cells to caspase 3 activation.
      Consistent with the observations using NIH/3T3 cells, downregulation of caveolin
      1 in T24 cells substantially diminishes caspase 3-like activity. Loss of
      sensitivity to apoptotic stimulation is recovered by inhibition of the
      phosphatidylinositol 3-kinase pathway using LY-294002, suggesting a possible
      mechanism for the sensitizing effect of caveolin-1. Thus our results suggest that
      caveolin-1 may act as a coupling or sensitizing factor in signaling apoptotic
      cell death in both fibroblastic (NIH/3T3) and epithelial (T24) cells.

PMID- 11245600
TI  - Cloning and functional expression of a liver isoform of the small conductance
      Ca2+-activated K+ channel SK3.
AB  - Small conductance Ca2+-activated K+ (SK) channels have been cloned from mammalian
      brain, but little is known about the molecular characteristics of SK channels in
      nonexcitable tissues. Here, we report the isolation from rat liver of an isoform
      of SK3. The sequence of the rat liver isoform differs from rat brain SK3 in five
      amino acid residues in the NH3 terminus, where it more closely resembles human
      brain SK3. SK3 immunoreactivity was detectable in hepatocytes in rat liver and in
      HTC rat hepatoma cells. Human embryonic kidney (HEK-293) cells transfected with
      liver SK3 expressed 10 pS K+ channels that were Ca2+ dependent (EC(50) 630 nM)
      and were blocked by the SK channel inhibitor apamin (IC(50) 0.6 nM); whole cell
      SK3 currents inactivated at membrane potentials more positive than -40 mV.
      Notably, the Ca2+ dependence, apamin sensitivity, and voltage-dependent
      inactivation of SK3 are strikingly similar to the properties of hepatocellular
      and biliary epithelial SK channels evoked by metabolic stress. These observations
      raise the possibility that SK3 channels influence membrane K+ permeability in
      hepatobiliary cells during liver injury.

PMID- 11245601
TI  - Regulation of SERCA Ca2+ pump expression by cytoplasmic Ca2+ in vascular smooth
      muscle cells.
AB  - Vascular smooth muscle cells (VSMC) express three isoforms of the sarcoplasmic or
      endoplasmic reticulum Ca2+-ATPase (SERCA) pump; SERCA2b predominates (91%),
      whereas SERCA2a (6%) and SERCA3 (3%) are present in much smaller amounts.
      Treatment with thapsigargin (Tg) or A-23187 increased the level of mRNA encoding
      SERCA2b four- to fivefold; SERCA3 increased about 10-fold, whereas SERCA2a was
      unchanged. Ca2+ chelation prevented the Tg-induced SERCA2b increase, whereas Ca2+
      elevation itself increased SERCA2b expression. These responses were discordant
      with those of 78-kDa glucose-regulated protein/immunoglobulin-binding protein
      (grp78/BiP), an endoplasmic reticulum stress-response protein. SERCA2b mRNA
      elevation was much larger than could be accounted for by the observed increase in
      message stability. The induction of SERCA2b by Tg did not require protein
      synthesis, nor was it affected by inhibitors of calcineurin, protein kinase C,
      Ca2+/calmodulin-dependent protein kinase, or tyrosine protein kinases. Treatment
      with the nonselective protein kinase inhibitor H-7 prevented Tg-induced SERCA2b
      expression from occurring, whereas another nonselective inhibitor, staurosporine,
      was without effect. We conclude that changes in cytosolic Ca2+ control the
      expression of SERCA2b in VSMC via a mechanism involving a currently
      uncharacterized, H-7-sensitive but staurosporine-insensitive, protein kinase.

PMID- 11245602
TI  - Potent NK1 antagonism by SR-140333 reduces rat colonic secretory response to
      immunocyte activation.
AB  - The potent neurokinin receptor 1 (NK1) antagonist SR-140333 has previously been
      shown to reduce castor oil-induced secretion in animal models. The importance of
      tachykinins in neuroimmune control of secretion and the effect of SR-140333 on
      key points in this pathway were elucidated in the present study to determine the
      type of intestinal dysfunction best targeted by this antagonist. Rat colonic
      secretion and substance P (SP) release were determined in vitro with the use of
      Ussing chamber and enzyme immunoassay techniques. NK1 receptors played a
      secretory role as receptor agonists stimulated secretion and SR-140333
      antagonized the response to SP response (pK(b) = 9.2). Sensory fiber stimulation
      released SP and evoked a large secretion that was reduced by 69% in the presence
      of SR-140333 (10 nM). Likewise, mastocytes also released SP. The subsequent
      secretory response was reduced by 43% in the presence of SR-140333 (50 nM). SP
      was also released from granulocytes; however, this did not cause secretion.
      Functional NK3 receptors were present in the colon as senktide stimulated
      secretion, an effect that was increased during stress. We conclude that NK3
      receptors may play a role in stress-related disorders, whereas NK1 receptors are
      more important in mast cell/afferent-mediated secretion.

PMID- 11245603
TI  - KCNQ4 channels expressed in mammalian cells: functional characteristics and
      pharmacology.
AB  - Human cloned KCNQ4 channels were stably expressed in HEK-293 cells and
      characterized with respect to function and pharmacology. Patch-clamp measurements
      showed that the KCNQ4 channels conducted slowly activating currents at potentials
      more positive than -60 mV. From the Boltzmann function fitted to the activation
      curve, a half-activation potential of -32 mV and an equivalent gating charge of
      1.4 elementary charges was determined. The instantaneous current-voltage
      relationship revealed strong inward rectification. The KCNQ4 channels were
      blocked in a voltage-independent manner by the memory-enhancing M current
      blockers XE-991 and linopirdine with IC(50) values of 5.5 and 14 microM,
      respectively. The antiarrhythmic KCNQ1 channel blocker bepridil inhibited KCNQ4
      with an IC(50) value of 9.4 microM, whereas clofilium was without significant
      effect at 100 microM. The KCNQ4-expressing cells exhibited average resting
      membrane potentials of -56 mV in contrast to -12 mV recorded in the
      nontransfected cells. In conclusion, the activation and pharmacology of KCNQ4
      channels resemble those of M currents, and it is likely that the function of the
      KCNQ4 channel is to regulate the subthreshold electrical activity of excitable
      cells.

PMID- 11245604
TI  - Glutathione protects chemokine-scavenging and antioxidative defense functions in
      human RBCs.
AB  - Oxidant stress, in vivo or in vitro, is known to induce oxidative changes in
      human red blood cells (RBCs). Our objective was to examine the effect of
      augmenting RBC glutathione (GSH) synthesis on 1) degenerative protein loss and 2)
      RBC chemokine- and free radical-scavenging functions in the oxidatively stressed
      human RBCs by using banked RBCs as a model. Packed RBCs were stored up to 84 days
      at 1-6 degrees C in Adsol or in the experimental additive solution (Adsol
      fortified with glutamine, glycine, and N-acetyl-L-cysteine). Supplementing the
      conventional additive with GSH precursor amino acids improved RBC GSH synthesis
      and maintenance. The rise in RBC gamma-glutamylcysteine ligase activity was
      directly proportional to the GSH content and inversely proportional to
      extracellular homocysteine concentration, methemoglobin formation, and losses of
      the RBC proteins band 3, band 4.1, band 4.2, glyceraldehyde-3-phosphate
      dehydrogenase, and Duffy antigen (P < 0.01). Reduced loss of Duffy antigen
      correlated well with a decrease in chemokine RANTES (regulated upon activation,
      normal T-cell expressed, and secreted) concentration. We conclude that the
      concomitant loss of GSH and proteins in oxidatively stressed RBCs can compromise
      RBC scavenging function. Upregulating GSH synthesis can protect RBC scavenging
      (free radical and chemokine) function. These results have implications not only
      in a transfusion setting but also in conditions like diabetes and sickle cell
      anemia, in which RBCs are subjected to chronic/acute oxidant stresses.

PMID- 11245605
TI  - Depletion of focal adhesion kinase by antisense depresses contractile activation
      of smooth muscle.
AB  - Focal adhesion kinase (FAK) undergoes tyrosine phosphorylation in response to the
      contractile stimulation of tracheal smooth muscle. We hypothesized that FAK may
      play an important role in signaling pathways that regulate smooth muscle
      contraction. FAK antisense or FAK sense was introduced into muscle strips by
      reversible permeabilization, and strips were incubated with antisense or sense
      for 7 days. Antisense decreased FAK expression compared with that in untreated
      and sense-treated tissues, but it did not affect the expression of vinculin or
      myosin light chain kinase. Increases in force, intracellular free Ca2+ and myosin
      light chain phosphorylation in response to stimulation with ACh or KCl were
      depressed in FAK-depleted tissues, but FAK depletion did not affect the
      activation of permeabilized tracheal muscle strips with Ca2+. The tyrosine
      phosphorylation of paxillin, a substrate for FAK, was also significantly reduced
      in FAK-depleted strips. We conclude that FAK is a necessary component of the
      signaling pathways that regulate smooth muscle contraction and that FAK plays a
      role in regulating intracellular free Ca2+ and myosin light chain
      phosphorylation.

PMID- 11245606
TI  - G protein coupling to M1 and M3 muscarinic receptors in sublingual glands.
AB  - Rat sublingual gland M2 and M3 muscarinic receptors each directly activate
      exocrine secretion. To investigate the functional role of coreceptor expression,
      we determined receptor-G protein coupling. Although membrane proteins of 40 and
      41 kDa are ADP-ribosylated by pertussis toxin (PTX), and 44 kDa proteins by
      cholera toxin (CTX), both carbachol-stimulated high-affinity GTPase activity and
      the GTP-induced shift in agonist binding are insensitive to CTX or PTX. Carbachol
      enhances photoaffinity labeling ([alpha-(32)P]GTP-azidoaniline) of only 42-kDa
      proteins that are subsequently tractable to immunoprecipitation by antibodies
      specific for Galpha(q) or Galpha(11) but not Galpha(12) or Galpha(13). Carbachol
      stimulated photoaffinity labeling as well as phosphatidylinositol 4,5
      bisphosphate (PIP2) hydrolysis is reduced 55% and 60%, respectively, by M1
      receptor blockade with m1-toxin. Galpha(q/11)-specific antibody blocks carbachol
      stimulated PIP2 hydrolysis. We also provide estimates of the molar ratios of
      receptors to Galpha(q) and Galpha(11). Although simultaneous activation of M1 and
      M3 receptors is required for a maximal response, both receptor subtypes are
      coupled to Galpha(q) and Galpha(11) to stimulate exocrine secretion via redundant
      mechanisms.

PMID- 11245607
TI  - Hypoxia-activated ligand HAL-1/13 is lupus autoantigen Ku80 and mediates lymphoid
      cell adhesion in vitro.
AB  - Hypoxia is known to induce extravasation of lymphocytes and leukocytes during
      ischemic injury and increase the metastatic potential of malignant lymphoid
      cells. We have recently identified a new adhesion molecule, hypoxia-activated
      ligand-1/13 (HAL-1/13), that mediates the hypoxia-induced increases in lymphocyte
      and neutrophil adhesion to endothelium and hypoxia-mediated invasion of
      endothelial cell monolayers by tumor cells. In this report, we used expression
      cloning to identify this molecule as the lupus antigen and DNA-dependent protein
      kinase-associated nuclear protein, Ku80. The HAL-1/13-Ku80 antigen is present on
      the surface of leukemic and solid tumor cell lines, including T and B lymphomas,
      myeloid leukemias, neuroblastoma, rhabdomyosarcoma, and breast carcinoma cells.
      Transfection and ectopic expression of HAL-1/13-Ku80 on (murine) NIH/3T3
      fibroblasts confers the ability of these normally nonadhesive cells to bind to a
      variety of human lymphoid cell lines. This adhesion can be specifically blocked
      by HAL-1/13 or Ku80-neutralizing antibodies. Loss of expression variants of these
      transfectants simultaneously lost their adhesive properties toward human lymphoid
      cells. Hypoxic exposure of tumor cell lines resulted in upregulation of HAL-1/13
      Ku80 expression at the cell surface, mediated by redistribution of the antigen
      from the nucleus. These studies indicate that the HAL-1/13-Ku80 molecule may
      mediate, in part, the hypoxia-induced adhesion of lymphocytes, leukocytes, and
      tumor cells.

PMID- 11245608
TI  - Insulin increases the turnover rate of Na+-K+-ATPase in human fibroblasts.
AB  - Insulin stimulates K+ transport by the Na+-K+-ATPase in human fibroblasts. In
      other cell systems, this action represents an automatic response to increased
      intracellular [Na+] or results from translocation of transporters from an
      intracellular site to the plasma membrane. Here we evaluate whether these
      mechanisms are operative in human fibroblasts. Human fibroblasts expressed the
      alpha(1) but not the alpha(2) and alpha(3) isoforms of Na+-K+-ATPase . Insulin
      increased the influx of Rb+, used to trace K+ entry, but did not modify the total
      intracellular content of K+, Rb+, and Na+ over a 3-h incubation period. Ouabain
      increased intracellular Na+ more rapidly in cells incubated with insulin, but
      this increase followed insulin stimulation of Rb+ transport. Bumetanide did not
      prevent the increased Na+ influx or stimulation of Na+-K+-ATPase. Stimulation of
      the Na+-K+-ATPase by insulin did not produce any measurable change in membrane
      potential. Insulin did not affect the affinity of the pump toward internal Na+ or
      the number of membrane-bound Na+-K+-ATPases, as assessed by ouabain binding. By
      contrast, insulin slightly increased the affinity of Na+-K+-ATPase toward
      ouabain. Phorbol esters did not mimic insulin action on Na+-K+-ATPase and
      inhibited, rather than stimulated, Rb+ transport. These results indicate that
      insulin increases the turnover rate of Na+-K+-ATPases of human fibroblasts
      without affecting their number on the plasma membrane or modifying their
      dependence on intracellular [Na+].

PMID- 11245609
TI  - Ca2+ mediates the effect of inhibition of Na+-K+-ATPase on the basolateral K+
      channels in the rat CCD.
AB  - We investigated the effect of inhibiting Na+-K+-ATPase on the basolateral 18-pS
      K+ channel in the cortical collecting duct (CCD) of the rat kidney. Inhibiting
      Na+-K+-ATPase with strophanthidin decreased the activity of the 18-pS K+ channel
      and increased the intracellular Ca2+ to 420 nM. Removal of extracellular Ca2+
      abolished the effect of strophanthidin. When intracellular Ca2+ was raised with 5
      microM ionomycin or A-23187 to 300, 400, and 500 nM, the activity of the 18-pS K+
      channel in cell-attached patches fell by 40, 85, and 96%, respectively. To
      explore the mechanism of Ca2+-induced inhibition, the effect of 400 nM Ca2+ on
      channel activity was studied in the presence of calphostin C, an inhibitor of
      protein kinase C, or KN-93 and KN-62, inhibitors of calmodulin-dependent kinase
      II. Addition of calphostin C or KN-93 or KN-62 failed to block the inhibitory
      effect of high concentrations of Ca2+ . This suggested that the inhibitory effect
      of high concentrations of Ca2+ was not mediated by protein kinase C or calmodulin
      dependent kinase II pathways. To examine the possibility that the inhibitory
      effect of high concentrations of Ca2+ was mediated by the interaction of nitric
      oxide with superoxide, we investigated the effect of 400 nM Ca2+ on channel
      activity in the presence of 4,5-dihydroxy-1,3-benzenedisulfonic acid (Tiron) or
      N(omega)-nitro-L-arginine methyl ester. Pretreatment of the tubules with 4,5
      dihydroxy-1,3-benzenedisulfonic acid or N(omega)-nitro-L-arginine methyl ester
      completely abolished the inhibitory effect of 400 nM Ca2+ on channel activity.
      Moreover, application of 4,5-dihydroxy-1,3-benzenedisulfonic acid reversed the
      inhibitory effect of strophanthidin. We conclude that the effect of inhibiting
      Na+-K+-ATPase is mediated by intracellular Ca2+ and the inhibitory effect of high
      concentrations of Ca2+ is the result of interaction of nitric oxide with
      superoxide.

PMID- 11245610
TI  - PKD in intestinal epithelial cells: rapid activation by phorbol esters, LPA, and
      angiotensin through PKC.
AB  - Protein kinase C (PKC) is implicated in the regulation of multiple important
      functions in intestinal epithelial cells, but the downstream signaling targets of
      PKCs in these cells remain poorly characterized. Here we report that treatment of
      normal rat intestinal cell lines IEC-6 and IEC-18 with phorbol 12,13-dibutyrate
      (PDBu) led to a rapid and striking PKC-dependent activation of protein kinase D
      (PKD; also known as PKCmu). Unlike conventional and novel PKCs, PKD did not
      undergo downregulation in response to prolonged (24 h) exposure of IEC-6 or IEC
      18 cells to PDBu. PKD was also rapidly activated in these cells by
      lysophosphatidic acid (LPA) or angiotensin in a concentration-dependent fashion
      via a PKC-dependent pathway. EC(50) values were 0.1 microM and 2 nM for LPA and
      angiotensin II, respectively. LPA-induced PKD activation was prevented
      selectively by treatment with pertussis toxin. PKD activation was tightly
      associated with an increase in PKD autophosphorylation at serine 916. Our results
      identify PKD as a novel early point of convergence and integration of G(i) and
      G(q) signaling in intestinal epithelial cells.

PMID- 11245611
TI  - Regulation of P2X(7) nucleotide receptor function in human monocytes by
      extracellular ions and receptor density.
AB  - P2X receptors function as ATP-gated cation channels. The P2X(7) receptor subtype
      is distinguished from other P2X family members by a very low affinity for
      extracellular ATP (millimolar EC50) and its ability to trigger induction of
      nonselective pores on repeated or prolonged stimulation. Previous studies have
      indicated that certain P2X(7) receptor-positive cell types, such as human blood
      monocytes and murine thymocytes, lack this pore-forming response. In the present
      study we compared pore formation in response to P2X(7) receptor activation in
      human blood monocytes with that in macrophages derived from these monocytes by in
      vitro tissue culture. ATP induced nonselective pores in macrophages but not in
      freshly isolated monocytes when both cell types were identically stimulated in
      standard NaCl-based salines. However, ion substitution studies revealed that
      replacement of extracellular Na+ and Cl- with K+ and nonhalide anions strongly
      facilitated ATP-dependent pore formation in monocytes. These ionic conditions
      also resulted in increased agonist affinity, such that 30-100 microM ATP was
      sufficient for activation of nonselective pores by P2X(7) receptors. Comparison
      of P2X(7) receptor expression in blood monocytes with that in macrophages
      indicated no differences in steady-state receptor mRNA levels but significant
      increases (up to 10-fold) in the amount of immunoreactive P2X(7) receptor protein
      at the cell surface of macrophages. Thus ability of ATP to activate nonselective
      pores in cells that natively express P2X(7) receptors can be modulated by
      receptor subunit density at the cell surface and ambient levels of extracellular
      Na+ and Cl-. These mechanisms may prevent adventitious P2X(7) receptor activation
      in monocytes until these proinflammatory leukocytes migrate to extravascular
      sites of tissue damage.

PMID- 11245612
TI  - Agouti regulates adipocyte transcription factors.
AB  - Agouti is a secreted paracrine factor that regulates pigmentation in hair
      follicle melanocytes. Several dominant mutations cause ectopic expression of
      agouti, resulting in a phenotype characterized by yellow fur, adult-onset obesity
      and diabetes, increased linear growth and skeletal mass, and increased
      susceptibility to tumors. Humans also produce agouti protein, but the highest
      levels of agouti in humans are found in adipose tissue. To mimic the human agouti
      expression pattern in mice, transgenic mice (aP2-agouti) that express agouti in
      adipose tissue were generated. The transgenic mice develop a mild form of
      obesity, and they are sensitized to the action of insulin. We correlated the
      levels of specific regulators of insulin signaling and adipocyte differentiation
      with these phenotypic changes in adipose tissue. Signal transducers and
      activators of transcription (STAT)1, STAT3, and peroxisome proliferator-activated
      receptor (PPAR)-gamma protein levels were elevated in the transgenic mice.
      Treatment of mature 3T3-L1 adipocytes recapitulated these effects. These data
      demonstrate that agouti has potent effects on adipose tissue. We hypothesize that
      agouti increases adiposity and promotes insulin sensitivity by acting directly on
      adipocytes via PPAR-gamma.

PMID- 11245613
TI  - Shear stress induces a time- and position-dependent increase in endothelial cell
      membrane fluidity.
AB  - Blood flow-associated shear stress may modulate cellular processes through its
      action on the plasma membrane. We quantified the spatial and temporal aspects of
      the effects of shear stress (tau) on the lipid fluidity of 1,1'-dihexadecyl
      3,3,3',3'-tetramethylindocarbocyanine perchlorate [DiIC(16)(13)]-stained plasma
      membranes of bovine aortic endothelial cells in a flow chamber. A confocal
      microscope was used to determine the DiI diffusion coefficient (D) by
      fluorescence recovery after photobleaching on cells under static conditions,
      after a step-tau of 10 or 20 dyn/cm(2), and after the cessation of tau. The
      method allowed the measurements of D on the upstream and downstream sides of the
      cell taken midway between the respective cell borders and the nucleus. In <10 s
      after a step-tau of 10 dyn/cm(2), D showed an upstream increase and a downstream
      decrease, and both changes disappeared rapidly. There was a secondary, larger
      increase in upstream D, which reached a peak at 7 min and decreased thereafter,
      despite the maintenance of tau. D returned to near control values within 5 s
      after cessation of tau. Downstream D showed little secondary changes throughout
      the 10-min shearing, as well as after its cessation. Further investigations into
      the early phase, with simultaneous measurements of upstream and downstream D,
      confirmed that a step-tau of 10 dyn/cm(2) elicited a rapid (5-s) but transient
      increase in upstream D and a concurrent decrease in downstream D, yielding a
      significant difference between the two sites. A step-tau of 20 dyn/cm(2) caused D
      to increase at both sites at 5 s, but by 30 s and 1 min the upstream D became
      significantly higher than the downstream D. These results demonstrate shear
      induced changes in membrane fluidity that are time dependent and spatially
      heterogeneous. These changes in membrane fluidity may have important implications
      in shear-induced membrane protein modulation.

PMID- 11245614
TI  - Activation of K+ channels induces apoptosis in vascular smooth muscle cells.
AB  - Intracellular K+ plays an important role in controlling the cytoplasmic ion
      homeostasis for maintaining cell volume and inhibiting apoptotic enzymes in the
      cytosol and nucleus. Cytoplasmic K+ concentration is mainly regulated by K+
      uptake via Na+-K+-ATPase and K+ efflux through K+ channels in the plasma
      membrane. Carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP), a
      protonophore that dissipates the H+ gradient across the inner membrane of
      mitochondria, induces apoptosis in many cell types. In rat and human pulmonary
      artery smooth muscle cells (PASMC), FCCP opened the large-conductance, voltage-
      and Ca2+-sensitive KK+ (maxi-K) channels, increased K+ currents through maxi-K
      channels [I(K(Ca))], and induced apoptosis. Tetraethylammonia (1 mM) and
      iberiotoxin (100 nM) decreased I(K(Ca)) by blocking the sarcolemmal maxi-K
      channels and inhibited the FCCP-induced apoptosis in PASMC cultured in media
      containing serum and growth factors. Furthermore, inhibition of K+ efflux by
      raising extracellular K+ concentration from 5 to 40 mM also attenuated PASMC
      apoptosis induced by FCCP and the K+ ionophore valinomycin. These results suggest
      that FCCP-mediated apoptosis in PASMC is partially due to an increase of maxi-K
      channel activity. The resultant K+ loss through opened maxi-K channels may serve
      as a trigger for cell shrinkage and caspase activation, which are major
      characteristics of apoptosis in pulmonary vascular smooth muscle cells.

PMID- 11245616
TI  - Ca2+-RhoA signaling pathway required for polyamine-dependent intestinal
      epithelial cell migration.
AB  - Expression of voltage-gated K(+) (Kv) channel genes is regulated by polyamines in
      intestinal epithelial cells (IEC-6 line), and Kv channel activity is involved in
      the regulation of cell migration during early restitution by controlling membrane
      potential (E(m)) and cytosolic free Ca2+ concentration ([Ca2+](cyt)). This study
      tests the hypothesis that RhoA of small GTPases is a downstream target of
      elevated ([Ca2+](cyt)) following activation of K(+) channels by increased
      polyamines in IEC-6 cells. Depletion of cellular polyamines by alpha
      difluoromethylornithine (DFMO) reduced whole cell K+ currents [I(K(v))] through
      Kv channels and caused membrane depolarization, which was associated with
      decreases in ([Ca2+](cyt)), RhoA protein, and cell migration. Exogenous polyamine
      spermidine reversed the effects of DFMO on I(K(v)), E(m), ([Ca2+](cyt)), and RhoA
      protein and restored cell migration to normal. Elevation of ([Ca2+](cyt)) induced
      by the Ca2+ ionophore ionomycin increased RhoA protein synthesis and stimulated
      cell migration, while removal of extracellular Ca2+ decreased RhoA protein
      synthesis, reduced protein stability, and inhibited cell motility. Decreased RhoA
      activity due to Clostridium botulinum exoenzyme C(3) transferase inhibited
      formation of myosin II stress fibers and prevented restoration of cell migration
      by exogenous spermidine in polyamine-deficient cells. These findings suggest that
      polyamine-dependent cell migration is partially initiated by the formation of
      myosin II stress fibers as a result of Ca2+-activated RhoA activity.

PMID- 11245617
TI  - Ontogenetic, gravity-dependent development of rat soleus muscle.
AB  - We tested the hypothesis that rat soleus muscle fiber growth and changes in
      myosin phenotype during the postnatal, preweaning period would be largely
      independent of weight bearing. The hindlimbs of one group of pups were unloaded
      intermittently from postnatal day 4 to day 21: the pups were isolated from the
      dam for 5 h during unloading and returned for nursing for 1 h. Control pups were
      either maintained with the dam as normal or put on an alternating feeding
      schedule as described above. The enlargement of mass (approximately 3 times),
      increase in myonuclear number (approximately 1.6 times) and myonuclear domain
      (approximately 2.6 times), and transformation toward a slow fiber phenotype (from
      56 to 70% fibers expressing type I myosin heavy chain) observed in controls were
      inhibited by hindlimb unloading. These properties were normalized to control
      levels or higher within 1 mo of reambulation beginning immediately after the
      unloading period. Therefore, chronic unloading essentially stopped the
      ontogenetic developmental processes of 1) net increase in DNA available for
      transcription, 2) increase in amount of cytoplasm sustained by that DNA pool, and
      3) normal transition of myosin isoforms that occur in some fibers from birth to
      weaning. It is concluded that normal ontogenetic development of a postural muscle
      is highly dependent on the gravitational environment even during the early
      postnatal period, when full weight-bearing activity is not routine.

PMID- 11245618
TI  - Predicted location and limited accessibility of protein kinase A phosphorylation
      site on Na-K-ATPase.
AB  - Regulation of Na-K-ATPase by cAMP-dependent protein kinase occurs in a variety of
      tissues. Phosphorylation of the enzyme's catalytic subunit at a classical
      phosphorylation consensus motif has been observed with purified enzyme.
      Demonstration of phosphorylation at the same site in normal living cells or
      tissues has been more difficult, however, making it uncertain that the Na-K
      ATPase is a direct physiological substrate of the kinase. Recently, the structure
      of the homologous sarco(endo)plasmic reticulum Ca-ATPase (SERCA1a) has been
      determined at 2.6 A resolution (Toyoshima C, Nakasako M, Nomura H, and Ogawa H.
      Nature 405: 647-655, 2000.), and the Na-K- ATPase should have the same fold.
      Here, the Na-K-ATPase sequence has been aligned with the Ca-ATPase structure to
      examine the predicted disposition of the phosphorylation site. The location is
      close to the membrane and partially buried by adjacent loops, and the site is
      unlikely to be accessible to the kinase in this conformation. Conditions that may
      expose the site or further bury it are discussed to highlight the issues facing
      future research on regulation of Na-K-ATPase by cAMP-dependent pathways.

PMID- 11245615
TI  - Ca2+-induced contraction of cat esophageal circular smooth muscle cells.
AB  - ACh-induced contraction of esophageal circular muscle (ESO) depends on Ca2+
      influx and activation of protein kinase Cepsilon (PKCepsilon). PKCepsilon,
      however, is known to be Ca2+ independent. To determine where Ca2+ is needed in
      this PKCepsilon-mediated contractile pathway, we examined successive steps in
      Ca2+-induced contraction of ESO muscle cells permeabilized by saponin. Ca2+ (0.2
      1.0 microM) produced a concentration-dependent contraction that was antagonized
      by antibodies against PKCepsilon (but not by PKCbetaII or PKCgamma antibodies),
      by a calmodulin inhibitor, by MLCK inhibitors, or by GDPbetas. Addition of 1
      microM Ca2+ to permeable cells caused myosin light chain (MLC) phosphorylation,
      which was inhibited by the PKC inhibitor chelerythrine, by D609
      [phosphatidylcholine-specific phospholipase C inhibitor], and by propranolol
      (phosphatidic acid phosphohydrolase inhibitor). Ca2+-induced contraction and
      diacylglycerol (DAG) production were reduced by D609 and by propranolol, alone or
      in combination. In addition, contraction was reduced by AACOCF(3) (cytosolic
      phospholipase A(2) inhibitor). These data suggest that Ca2+ may directly activate
      phospholipases, producing DAG and arachidonic acid (AA), and PKCepsilon, which
      may indirectly cause phosphorylation of MLC. In addition, direct G protein
      activation by GTPgammaS augmented Ca2+-induced contraction and caused dose
      dependent production of DAG, which was antagonized by D609 and propranolol. We
      conclude that agonist (ACh)-induced contraction may be mediated by activation of
      phospholipase through two distinct mechanisms (increased intracellular Ca2+ and G
      protein activation), producing DAG and AA, and activating PKCepsilon-dependent
      mechanisms to cause contraction.

PMID- 11245619
TI  - Caloxin: a novel plasma membrane Ca2+ pump inhibitor.
AB  - Plasma membrane (PM) Ca2+ pump is a Ca+-Mg2+-ATPase that expels Ca2+ from cells
      to help them maintain low concentrations of cytosolic Ca2+ . There are no known
      extracellularly acting PM Ca2+ pump inhibitors, as digoxin and ouabain are for
      Na+ pump. In analogy with digoxin, we define caloxins as extracellular PM Ca2+
      pump inhibitors and describe caloxin 2A1. Caloxin 2A1 is a peptide obtained by
      screening a random peptide phage display library for binding to the second
      extracellular domain (residues 401-413) sequence of PM Ca2+ pump isoform 1b.
      Caloxin 2A1 inhibits Ca2+-Mg2+-ATPase in human erythrocyte leaky ghosts, but it
      does not affect basal Mg2+-ATPase or Na+-K+-ATPase in the ghosts or Ca2+-Mg2+
      ATPase in the skeletal muscle sarcoplasmic reticulum. Caloxin 2A1 also inhibits
      Ca2+-dependent formation of the 140-kDa acid-stable acylphosphate, which is a
      partial reaction of this enzyme. Consistent with inhibition of the PM Ca2+ pump
      in vascular endothelium, caloxin 2A1 produces an endothelium-dependent relaxation
      that is reversed by N(G)-nitro-L-arginine methyl ester. Thus caloxin 2A1 is a
      novel PM Ca2+ pump inhibitor selected for binding to an extracellular domain.

PMID- 11245620
TI  - Man Is not a rodent: aquaporins in the airways.

PMID- 11245621
TI  - Expression and localization of epithelial aquaporins in the adult human lung.
AB  - Aquaporins (AQPs) facilitate water transport across epithelia and play an
      important role in normal physiology and disease in the human airways. We used in
      situ hybridization and immunofluorescence to determine the expression and
      cellular localization of AQPs 5, 4, and 3 in human airway sections. In nose and
      bronchial epithelia, AQP5 is expressed at the apical membrane of columnar cells
      of the superficial epithelium and submucosal gland acinar cells. AQP4 was
      detected in basolateral membranes in ciliated ducts and by in situ in gland
      acinar cells. AQP3 is present on basal cells of both superficial epithelium and
      gland acinus. In these regions AQPs 5, 4, and 3 are appropriately situated to
      permit transepithelial water permeability. In the small airways (proximal and
      terminal bronchioles) AQP3 distribution shifts from basal cell to surface
      expression (i.e., localized to the apical membrane of proximal and terminal
      bronchioles) and is the only AQP identified in this region of the human lung. The
      alveolar epithelium has all three AQPs represented, with AQP5 and AQP4 localized
      to type I pneumocytes and AQP3 to type II cells. This study describes an
      intricate network of AQP expression that mediates water transport across the
      human airway epithelium.

PMID- 11245622
TI  - Lung fibroblasts improve differentiation of rat type II cells in primary culture.
AB  - Epithelial-mesenchymal interactions mediate prenatal lung morphogenesis and
      differentiation, yet little is known about their effects in the adult. In this
      study we have examined the influence of cocultured lung fibroblasts on rat
      alveolar type II cell differentiation in primary culture. Type II cells that were
      co-cultured with lung fibroblasts showed significant increases in messenger RNA
      (mRNA) levels of surfactant protein (SP)-A, SP-B, SP-C, and SP-D. Metabolic
      labeling and immunohistochemistry demonstrated that these mRNAs were translated
      and processed. Addition of 10(-7) M dexamethasone (DEX) to cocultures antagonized
      the effects of the fibroblasts on SP-A and SP-C, but significantly augmented the
      effects on SP-B; expression of SP-D was unaffected. Coculture of type II cells
      with lung fibroblasts also increased acetate incorporation into phospholipids 10
      fold, which was antagonized by DEX. Keratinocyte growth factor (KGF) mimicked the
      effects of lung fibroblasts on SP gene expression, but KGF neutralizing
      antibodies only partially reduced the effects of lung fibroblasts. KGF increased
      acetate incorporation into surfactant phospholipids, and the addition of DEX
      augmented this response. Together, our observations suggest that epithelial-
      mesenchymal interactions affect type II cell differentiation in the adult lung,
      and that these effects are partially mediated by KGF.

PMID- 11245623
TI  - Na,K-ATPase gene transfer mitigates an oxidant-induced decrease of active sodium
      transport in rat fetal ATII cells.
AB  - We investigated whether adenovirus-mediated transfer of genes encoding for
      subunits of the Na,K-ATPase increases transepithelial Na(+) transport in rat
      fetal distal lung epithelial (FDLE) monolayers and renders them more resistant to
      hydrogen peroxide injury. FDLE cells, isolated from rat fetuses at a gestational
      age of 19 to 20 d (22 d = term), were seeded on filters and infected with
      replication-incompetent human type 5 adenoviruses containing complementary DNAs
      encoding for rat Na,K-ATPase alpha(1) or beta(1) subunits (ad alpha(1) and ad
      beta(1), respectively). Once confluent monolayers were formed, the filters were
      mounted in Ussing chambers and short circuit currents (I(SC)) were measured.
      Increased levels of alpha(1) or beta(1) subunit proteins after infection with ad
      alpha(1) and ad beta(1), respectively, were confirmed by Western blot analysis.
      Baseline I(SC) increased after transfection with 2 plaque-forming units (pfu) of
      ad beta(1) from 5.1 +/- 0.3 to 6.1 +/- 0.3 microA/cm(2) (mean +/- SEM; P < 0.05).
      Permeabilization of the apical membrane with amphotericin B caused a large
      increase in I(SC); the ouabain-sensitive component of the amphotericin B-elicited
      I(SC) (ouab(max)) was increased from 4.0 +/- 0.2 (n = 69) in controls to 4.8 +/-
      0.2 (n = 15), 5.9 +/- 0.3 (n = 53), 6.9 +/- 0.4 (n = 25), 7.7 +/- 0.9 (n = 16) in
      monolayers infected with 1, 2, 11, and 22 pfu of ad beta(1), respectively;
      transfection with ad alpha(1) had no effect on any measured variables. Further,
      transfection with ad beta(1) in comparison to noninfected monolayers resulted in
      higher baseline and ouab(max) I(SC) after injury with 500 microM H(2)O(2). We
      conclude that overexpression of the beta(1) subunit of the Na,K-ATPase may help
      maintain normal levels of vectorial Na(+) transport across ATII cell monolayers
      in pathologic conditions.

PMID- 11245624
TI  - Post-translational processing of surfactant protein-C proprotein: targeting
      motifs in the NH(2)-terminal flanking domain are cleaved in late compartments.
AB  - Rat surfactant protein (SP)-C is a 3.7-kD hydrophobic lung-specific protein
      generated from proteolytic processing of a 21-kD propeptide (SP-C(21)). We have
      demonstrated that initial post-translational processing of SP-C(21) involves two
      cleavages of the COOH-terminus (Beers and colleagues, J. Biol. Chem.
      1994;269:20,318--20,328). The goal of the current study was to define processing
      and function of the NH(2)-terminal flanking domain. Epitope-specific antisera
      directed against spatially distinct regions of the NH(2) terminus, NPROSP-C(2-9)
      (epitope = D(2)-L(9)) and NPROSP-C(11-23) (= E(11)-Q(23)) were produced. By
      Western blotting, both antisera identified SP-C(21) in microsomes. A 6-kD form
      (SP-C(6)), enriched in lamellar bodies (LBs), was detected only by NPROSP-C(11
      23) and not extractable with NaCO(3) treatment. Immunogold staining of ultrathin
      lung sections with NPROSP-C(11-23) identified proSP-C in both multivesicular
      bodies (mvb) and LBs whereas NPROSP-C(2-9) labeled only mvb. (35)S-pulse chase
      analysis demonstrated synthesis of SP-C(21) and three intermediate forms (SP
      C(16), SP-C(7), and SP-C(6)). Complete processing involved four separate
      cleavages with a precursor- product relationship between the low molecular weight
      forms SP-C(7) and SP-C(6). Fluorescence microscopy of A549 cells expressing
      fusion proteins of enhanced green fluorescent protein (EGFP) and proSP-C NH(2)
      terminal deletion mutants showed targeting of EGFP/SP-C(1-194) and EGFP/SP-C(10
      194) to early endosomal antigen-1-negative, CD-63-positive cytoplasmic vesicles
      whereas EGFP/SP-C(19-194), EGFP/SP-C(Delta 10-18), and EGFP/SP-C(24-194) were
      restricted to the endoplasmic reticulum (ER). We conclude that synthetic
      processing includes a previously unrecognized cleavage of the proximal NH(2)
      terminus (M(1)-L(9)), which occurs after removal of COOH-flanking domains (H(59)
      I(194)) but before packaging in LBs, and that the region M(10)-T(18) is required
      for targeting of proSP-C to post-ER vesicular compartments in the biosynthetic
      pathway.

PMID- 11245625
TI  - Role of osteopontin in the pathogenesis of bleomycin-induced pulmonary fibrosis.
AB  - Pulmonary fibrosis is initiated by migration, adhesion, and proliferation of
      fibroblasts. Osteopontin (OPN) is one of the cytokines produced by activated
      macrophages and mediates various functions, including cell attachment and
      migration, by interacting with alphav integrin. In this study, we have
      investigated the role of OPN in the pathogenesis of pulmonary fibrosis. We
      developed a mouse model for pulmonary fibrosis by intratracheal instillation of
      bleomycin (BLM). OPN was strongly expressed in alveolar macrophages accumulating
      in the fibrotic area of the lung. OPN messenger RNA (mRNA) in the lung was
      notably induced by BLM instillation, and the development of the fibrotic process
      was associated with an increase in the expression of OPN mRNA and protein. In
      vitro, recombinant OPN enhanced migration, adhesion, and platelet-derived growth
      factor (PDGF)-mediated DNA synthesis of murine fibroblast cell line NIH3T3. These
      effects of OPN on fibroblasts were significantly suppressed by addition of
      antimouse alphav integrin monoclonal antibody (RMV-7). Furthermore, treatment of
      mice with RMV-7 repressed the extent of pulmonary fibrosis in this model.
      Conclusively, these data suggest that OPN produced by alveolar macrophages
      functions as a fibrogenic cytokine that promotes migration, adhesion, and
      proliferation of fibroblasts in the development of BLM-induced pulmonary
      fibrosis.

PMID- 11245626
TI  - Early events in naphthalene-induced acute Clara cell toxicity. II. Comparison of
      glutathione depletion and histopathology by airway location.
AB  - One of the presumed roles of intracellular glutathione (GSH) is the protection of
      cells from injury by reactive intermediates produced by the metabolism of
      xenobiotics. To establish whether GSH depletion is a critical step in the
      initiation of events that lead to cytotoxicity by P450-activated cytotoxicants,
      naphthalene, a well-defined Clara cell cytotoxicant, was administered to mice
      (200 mg/kg) by intraperitoneal injection. Shortly after injection (1, 2, and 3
      h), intracellular GSH content was assessed by high performance liquid
      chromatography or quantitative epifluorescent imaging microscopy and compared
      with the degree of cytotoxicity as assessed by high resolution histopathology. In
      highly susceptible airways (distal bronchioles), GSH decreased by 50% in 1 h.
      Cytoplasmic vacuolization was not visible until 2 h, when GSH had decreased by an
      additional 50%. By 3 h, cytoplasmic blebbing was extensive. In minimally
      susceptible airways (lobar and proximal bronchi), GSH depletion varied widely
      within the population; a small proportion of the cells lost greater than 50% of
      their GSH by 2 h and a significant percentage of the cells retained most of their
      GSH throughout the entire 3 h. Cytoplasmic vacuolization was apparent in some of
      the cells at 2 h but not visible in any cells at 3 h. We conclude that (1) loss
      of intracellular GSH is an early event that precedes initial signs of cellular
      damage in Clara cell cytotoxicity; (2) this pattern of loss in relation to early
      injury is found both in highly susceptible and minimally susceptible airway
      sites; (3) there is wide cell-to-cell heterogeneity in the response; (4) the
      heterogeneity in the response profile varies between populations in highly
      susceptible and minimally susceptible sites; and (5) once the intracellular GSH
      concentration within the entire cell population drops below a certain threshold,
      the initial phase of injury becomes irreversible.

PMID- 11245627
TI  - Initiation of apoptosis by actin cytoskeletal derangement in human airway
      epithelial cells.
AB  - Changes in epithelial cell shape can lead to cell death and detachment. Actin
      filaments are cleaved during apoptosis, but whether disruption in the actin
      cytoskeletal network, as one manifestation of cell shape change, can itself
      induce apoptosis is not known. We tested this hypothesis in the airway epithelial
      cell line 1HAEo(-) and in primary airway epithelial cells by preventing actin
      filament elongation with cytochalasin D or by aggregating actin filaments with
      jasplakinolide. Disruption of actin filament integrity promptly induced apoptosis
      in adherent epithelial cells within 5 h. Jasplakinolide-induced apoptosis did not
      disrupt focal adhesions, whereas cytochalasin D-induced apoptosis decreased focal
      adhesion protein expression and occurred despite ligation of the fibronectin
      receptor. Death induction was abrogated by the caspase inhibitors z-VAD-fmk and
      Ac-DEVD-cho but not by blocking the Fas (CD95) receptor. Whereas cytochalasin D-
      induced apoptosis was associated with cleavage of pro-caspase-8, jasplakinolide
      induced apoptosis was not. Both agents induced formation of a death-inducing
      signaling complex. These data demonstrate that disruption of actin filament
      integrity with either cytochalasin D or jasplakinolide induces apoptosis in
      airway epithelial cells but by different mechanisms, and suggest that actin may
      be an early modulator of apoptotic commitment.

PMID- 11245628
TI  - Expression of heme oxygenase in human airway epithelial cells.
AB  - Elevated levels of carbon monoxide (CO) are found in the exhaled breath of
      patients with inflammatory diseases such as asthma and cystic fibrosis.
      Endogenous CO is derived from heme oxygenase (HO) (EC 1.14.99.3), which
      catabolizes heme-producing CO and biliverdin. There are three isoforms of HO: HO
      1 is inducible by inflammatory cytokines and oxidants, including nitric oxide
      (NO), whereas HO-2 and HO-3 are expressed constitutively. Primary airway
      epithelial cells were treated with either 50 ng/ml interleukin-1 beta, tumor
      necrosis factor-alpha, and interferon-gamma (cytomix), or the NO donor NOC-18 for
      up to 24 h. Cytomix-induced HO-1 expression peaked at 4 h, returning to baseline
      by 24 h, whereas HO-2 expression remained unchanged. This increase in HO-1
      expression could not be explained by an increase in NO production as inducible NO
      synthase expression increased between 12 and 24 h. However, the NO donor NOC-18
      (500 microM) increased HO-1 expression twofold and HO activity 25-fold, whereas
      cytomix treatment increased HO activity eightfold. NO induction of HO-1 was not
      mediated via guanylyl cyclase and was not attenuated by 1 microM dexamethasone,
      although dexamethasone increased HO-2 protein. Therefore, airway epithelial cells
      express HO-2 and can express HO-1; thus, the epithelium may be a source of
      increased CO in airway diseases.

PMID- 11245629
TI  - Inhibition of eosinophilic inflammation in allergen-challenged TNF receptor
      p55/p75--and TNF receptor p55-deficient mice.
AB  - To determine the relative in vivo importance of tumor necrosis factor (TNF)
      release after allergen challenge to the subsequent endothelial adhesion and
      recruitment of eosinophils, we have compared eosinophil recruitment in TNF
      receptor p55/p75--deficient, TNF receptor p55--deficient, and control wild-type
      mice challenged with allergen. Bronchoalveolar lavage eosinophil recruitment in
      TNF receptor p55/p75--deficient and TNF receptor p55--deficient mice challenged
      with ovalbumin was significantly reduced compared with wild-type mice. To
      determine the mechanism of inhibition of eosinophil recruitment in TNF receptor
      deficient mice, we used intravital microscopy to visualize the rolling and firm
      adhesion of fluorescently labeled mouse eosinophils in the microvasculature of
      the allergen-challenged mouse mesentery. Eosinophil rolling as well as eosinophil
      firm adhesion to endothelium were significantly inhibited in allergen-challenged
      TNF receptor p55/p75--deficient and TNF receptor p55--deficient mice compared
      with wild-type mice. Overall, these studies demonstrate that TNF, released after
      allergen challenge, is important in the induction of endothelial cell
      adhesiveness, a prerequisite for recruitment of circulating eosinophils.

PMID- 11245630
TI  - Granulocyte macrophage colony-stimulating factor and interleukin-5 activate STAT5
      and induce CIS1 mRNA in human peripheral blood eosinophils.
AB  - In these studies, we examined signaling through the transcription factor STAT5 in
      human peripheral blood eosinophils after treatment with granulocyte macrophage
      colony-stimulating factor (GM-CSF) or interleukin (IL)-5. In response to either
      cytokine, STAT5 was rapidly tyrosine phosphorylated and acquired interferon gamma
      activation site (GAS) DNA binding activity. Tyrosine-phosphorylated STAT5 was
      associated with both cytosolic and nuclear cell fractions. Consistent with
      activation, the transcription of a STAT5-dependent gene, cytokine inducible, SH2
      containing protein (CIS1), was enhanced after cytokine stimulation. This is the
      first report of IL-5 regulation of CIS1 gene expression in any cell type. Given
      its role in cytokine signaling, CIS1 upregulation may serve to attenuate IL-5 and
      GM-CSF modulation of eosinophil function. These data suggest that active nuclear
      STAT5 participates in the regulation of IL-5 and GM-CSF--inducible genes in
      stimulated human peripheral blood eosinophils.

PMID- 11245631
TI  - Nitric oxide inhibits rhinovirus-induced granulocyte macrophage colony
      stimulating factor production in bronchial epithelial cells.
AB  - Infection of asthmatics with human rhinovirus (HRV) enhances airway eosinophilia
      and airways hyperreactivity. The current studies were performed to further
      characterize HRV-induced generation by human bronchial epithelial cells of
      granulocyte macrophage colony-stimulating factor (GM-CSF), a cytokine that could
      contribute to airway eosinophilia by increasing the survival and activation of
      eosinophils, and to determine the effects of the antiviral agent nitric oxide
      (NO) on HRV-induced GM-CSF production. Maximal levels of messenger RNA (mRNA) for
      GM-CSF were seen 1 h after HRV infection. Expression was sustained through 24 h
      and declined by 48 h. GM-CSF protein was detected in cell supernatants by 2 h
      after infection and reached maximal concentrations by 24 h, with the most rapid
      rate of production occurring from 2 to 7 h. The NO donor 3-(2-hydroxy-2-nitroso-1
      propyl-hydrazino)-1-propanamine (NONOate) inhibited HRV-induced GM-CSF protein
      production in a time- and dose-dependent fashion. NONOate also inhibited HRV
      induced GM-CSF mRNA levels at both times (1 and 4 h) examined. NONOate increased
      GM-CSF mRNA stability, suggesting that reduced mRNA levels were due to inhibition
      of transcription. The transcription factor nuclear factor-kappa B was rapidly
      induced by HRV infection, but was not inhibited by NONOate, implying a role for
      other transcription factors. Thus, NO may play an important anti-inflammatory
      role in virally induced exacerbations of diseases such as asthma.

PMID- 11245632
TI  - Alveolar macrophage cell line MH-S is valuable as an in vitro model for
      Legionella pneumophila infection.
AB  - Alveolar macrophages are the preferential site for growth of Legionella
      pneumophila (Lp) during infection. However, the study of Lp infection in alveolar
      macrophages is difficult due to the limitation of available primary alveolar
      macrophages. In the present study, we established an in vitro Lp infection model
      in alveolar macrophages using a continuous cell line of murine alveolar
      macrophages designated MH-S. Infection of both MH-S cells and primary mouse
      alveolar macrophages obtained by alveolar lavage with virulent L. pneumophila (Lp
      V) showed vigorous growth of the bacteria, but infection with avirulent L.
      pneumophila (Lp-Av) resulted in only minimum growth. Cytokine message expression
      determination in the MH-S cells after infection showed strong induction of
      interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha messages induced by Lp
      V but minimal induction of these cytokines by Lp-Av infection. IL-1 alpha protein
      secretion and the message levels for IL-1 alpha were also analyzed, and
      remarkable induction of IL-1 alpha was evident in both macrophage types when
      infected with Lp-V. Analysis of IL-12 p40 responses of both macrophage types to
      Lp-V infection assessed by reverse transcriptase/polymerase chain reaction
      revealed induction of increased message levels, but significant levels were
      induced only slowly. Determination of IL-12 protein secretion by enzyme-linked
      immunosorbent assay of culture supernatants from both macrophage types infected
      with either Lp-V or Lp-Av showed only minimum production. Thus, MH-S alveolar
      macrophages showed a similar response to Lp infection compared with primary
      alveolar macrophages and can be a useful in vitro model system to study Lp
      infection. The study also revealed the restricted IL-12 protein secretion of
      alveolar macrophages by Lp infection.

PMID- 11245633
TI  - Human gamma/delta T-cell lines derived from airway biopsies.
AB  - gamma/delta T cells have been postulated to play an important role in the immune
      response at epithelial boundaries, but have not been well described in human lung
      tissue. We have identified and characterized gamma/delta T-cell lines from human
      airway biopsies and compared them with T-cell lines from paired peripheral blood
      samples. Airway-derived T-cell lines stimulated with tetanus toxoid (TT)
      contained a greater proportion of gamma/delta T cells compared with T-cell lines
      stimulated with mitogens, other antigens, or without antigen. TT-stimulated
      airway T cells expressed different T-cell receptors (TCRs) than did blood-
      derived T cells, and used predominantly variable region (V)gamma I family genes
      rather than V gamma II family genes. Airway-derived gamma/delta T cells produced
      high levels of interferon-gamma and were associated with T helper 1--like
      cytokine profiles. This study describes the presence and antigen-dependent
      proliferation of gamma/delta T cells from human airway tissue, and demonstrates
      differences in lung-derived gamma/delta TCRs compared with gamma/delta T cells
      derived from peripheral blood. The data suggest that gamma/delta T cells may be
      functionally enriched in human airways relative to peripheral blood.

PMID- 11245634
TI  - Induction and regulation of the carcinogen-metabolizing enzyme CYP1A1 by
      marijuana smoke and delta (9)-tetrahydrocannabinol.
AB  - Induction of the carcinogen-metabolizing enzyme cytochrome P4501A1 (CYP1A1) is a
      key step in the development of tobacco-related cancers. To determine if marijuana
      smoke activates CYP1A1, a murine hepatoma cell line expressing an inducible
      CYP1A1 gene (Hepa-1) was exposed in vitro to tar extracts prepared from either
      tobacco, marijuana, or placebo marijuana cigarettes. Marijuana tar induced higher
      levels of CYP1A1 messenger RNA (mRNA) than did tobacco tar, yet resulted in much
      lower CYP1A1 enzyme activity. These differences between marijuana and tobacco
      were primarily due to Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the
      psychoactive component of marijuana. Here we show that Delta(9)-THC acts through
      the aryl hydrocarbon receptor complex to activate transcription of CYP1A1. A 2
      microg/ml concentration of Delta(9)-THC produced an average 2.5-fold induction of
      CYP1A1 mRNA, whereas a 10- microg/ml concentration of Delta(9)-THC produced a 4.3
      fold induction. No induction was observed in Hepa-1 mutants lacking functional
      aryl-hydrocarbon receptor or aryl-hydrocarbon receptor nuclear translocator
      genes. At the same time, Delta(9)-THC competitively inhibited the CYP1A1 enzyme,
      reducing its ability to metabolize other substrates. Spiking tobacco tar with
      Delta(9)-THC resulted in a dose-dependent decrease in the ability to generate
      CYP1A1 enzyme activity as measured by the ethoxyresorufin-o-deethylase (EROD)
      assay. This inhibitory effect was confirmed by Michaelis-Menton kinetic analyses
      using recombinant human CYP1A1 enzyme expressed in insect microsomes. This
      complex regulation of CYP1A1 by marijuana smoke and the Delta(9)-THC that it
      contains has implications for the role of marijuana as a cancer risk factor.

PMID- 11245635
TI  - Airway administration of Escherichia coli endotoxin to mice induces
      glucocorticosteroid-resistant bronchoconstriction and vasopermeation.
AB  - The effects of the administration of Escherichia coli endotoxin
      (lipopolysaccharide, LPS) into the airways of C57Bl/6 mice were studied.
      Neutrophil sequestration in the lungs and their enrichment, together with tumor
      necrosis factor (TNF)-alpha, in bronchoalveolar lavage fluid (BALF) were
      associated with bronchoconstriction and bronchopulmonary hyperreactivity (BHR) to
      methacholine and alveolocapillary dysfunction. Granulocyte depletion by the
      myelotoxic drug vinblastine failed to modify TNF-alpha production and prevented
      LPS-induced neutrophil recruitment to lungs and BALF, bronchoconstriction, and
      BHR. Neutrophils were again sequestered in the lungs when LPS was administered 4
      to 5 d after vinblastine, whereas inhibition of their passage to BALF persisted.
      Under those conditions, bronchoconstriction and BHR by LPS also recovered,
      showing that these functional effects are independent from BALF neutrophil
      enrichment but require lung sequestration. Administration of granulocyte colony
      stimulating factor after vinblastine counteracted its effects and allowed the
      recovery of lung neutrophil sequestration by LPS and a partial recovery of
      bronchoconstriction under conditions where neutrophils still failed to migrate to
      BALF. Dexamethasone (the phosphate salt and its free base) suppressed LPS-induced
      TNF-alpha generation in BALF and its neutrophil enrichment, whereas neutrophil
      lung sequestration, bronchoconstriction, BHR, and alveolocapillary dysfunction
      were marginally reduced and only so at low doses of dexamethasone, higher doses
      being inactive or aggravating. In situ neutrophil activation could account for
      LPS-induced bronchoconstriction and BHR, both of which are refractory to steroids
      and appear to be mediated by unrelated mechanisms, which may be relevant for
      acute respiratory distress syndrome, a condition for which LPS administration is
      used as a model.

PMID- 11245636
TI  - Degranulation status of airway tissue eosinophils in mouse models of allergic
      airway inflammation.
AB  - Eosinophil degranulation is a characteristic feature of asthma and allergic
      rhinitis. However, degranulated eosinophils have not been convincingly
      demonstrated in the common mouse models of these airway diseases. This study uses
      eosinophil peroxidase (EPO) histochemistry and transmission electron microscopy
      (TEM) analysis to assess eosinophil degranulation in the airways of ovalbumin
      (OVA)-sensitized and challenged BALB/c and C57BL/6 mice. Using TEM we also
      examined mouse and human blood eosinophils after in vitro incubation with formyl
      Met-Leu-Phe (fMLP) or phorbol myristate acetate (PMA). Although OVA exposure
      induced significant nasal and lung eosinophilia, we did not observe any of the
      known cellular processes by which eosinophils release their granule products,
      i.e., eosinophil cytolysis, piecemeal degranulation, and exocytosis. The
      occurrence of other allergen-induced degranulation events was ruled out because
      no difference in granule morphology was observed between lung-tissue eosinophils
      and blood or bone-marrow eosinophils from control animals. Accordingly, there was
      no detectable extracellular EPO in lung tissues of allergic mice. Similarly,
      mouse blood eosinophils remained nondegranulated in vitro in the presence of fMLP
      and PMA, whereas the same treatment of human eosinophils resulted in extensive
      degranulation. This investigation indicates that OVA-induced airway inflammation
      in the present mouse strains does not involve significant eosinophil
      degranulation. It is speculated that this dissimilarity from the human disease
      may be due to a fundamental difference in the regulation of mouse and human
      eosinophils.

PMID- 11245637
TI  - Implantable cardioverter-defibrillator: A Volkswagen or a Rolls Royce: how much
      will we pay to save a life?

PMID- 11245638
TI  - Mechanotransduction in cardiomyocyte hypertrophy.

PMID- 11245639
TI  - Effects of urotensin II in human arteries and veins of varying caliber.
AB  - BACKGROUND: -Urotensin II (UII) is the ligand for the GPR14 receptor and the most
      potent vasoconstrictor in the cynomolgus monkey. UII also contracts rat thoracic
      aorta. We studied the effect of human UII (hUII) in human blood vessels Methods
      and Results-Small subcutaneous resistance arteries, internal mammary arteries,
      saphenous veins, and small subcutaneous veins were studied using standard
      techniques. Subcutaneous resistance arteries constricted in response to
      norepinephrine (maximum tension, 2.84+/-0.38 mN/mm; the concentration required to
      produce 50% of the maximum response [EC(50)], 0.52+/-0.07 micromol/L) and
      endothelin-1 (maximum tension, 4.19+/-0.93 mN/mm; EC(50), 1.6+/-0.1 nmol/L). hUII
      did not contract these arteries, internal mammary arteries, or either type of
      vein, but it was a potent vasoconstrictor in rat thoracic aorta (maximum tension,
      2.36+/-0.2 mN/mm; EC(50), 1.13+/-0.36 nmol/L). CONCLUSIONS: -hUII has no
      vasoconstrictor action in human arteries and veins of different sizes and
      vascular beds. Marked species differences in the actions of UII question its
      importance in human cardiovascular regulation.

PMID- 11245640
TI  - Effect of testosterone on plaque development and androgen receptor expression in
      the arterial vessel wall.
AB  - BACKGROUND: -Recent studies have suggested that testosterone has a protective
      effect in the arterial vascular system. However, little is known about the
      molecular aspects of the mechanism(s) involved in these processes. The aim of the
      present study was to investigate the effect of testosterone on neointimal plaque
      development and on the expression of the vascular androgen receptor. Methods and
      Results-Neointimal plaque formation was induced by endothelial denudation in the
      aortas of male New Zealand White rabbits. Aortic ring segments were cultured for
      21 days after endothelial denudation. Testosterone was applied to the culture
      medium in different doses. Compared with the non-hormone-treated control group, a
      significant inhibition of neointimal plaque development (expressed as the
      intima/media ratio) was found at testosterone concentrations of 10 ng/mL
      (P:=0.037) and 100 ng/mL (P:=0.012; intima/media ratios: median of controls,
      0.25; median of 10 ng/mL testosterone group, 0.15; median of 100 ng/mL
      testosterone group, 0.16). Associated with this inhibitory effect on plaque size
      was a 50% increase of the amount of androgen receptor mRNA in the arterial
      segments treated with testosterone. CONCLUSION: -The beneficial effects of
      testosterone on postinjury plaque development underlines, at least in males, the
      important role of androgens in the vascular system. As our data suggest, the
      vascular androgen receptor is probably involved in these processes. Further
      studies are required to characterize the androgen receptor-dependent pathways in
      the vascular system.

PMID- 11245641
TI  - Thrombomodulin Ala455Val polymorphism and risk of coronary heart disease.
AB  - BACKGROUND: Thrombomodulin (TM) is expressed on the endothelial surface and plays
      an important role in vasoprotection. A common polymorphism of TM at amino acid
      position 455 with an alanine (A) to valine (V) transition was previously reported
      to be associated cross-sectionally with acute myocardial infarction. Whether this
      single nucleotide polymorphism predicts risk of developing coronary heart disease
      (CHD) is unclear. METHODS AND RESULTS: Within a large cohort study, we identified
      467 incident CHD cases during an average of 5 years of follow-up. We determined
      TM-455 genotypes on 376 CHD cases (23% black, 77% white) and a reference sample
      of 461. The AA genotype was significantly more prevalent in noncases than in
      cases (P:=0.016). The prevalences of the AA genotype in noncase blacks and whites
      were 93% and 67%, respectively. The AA genotype frequency was significantly
      reduced in black cases versus noncases (P:=0.018). It was also lower in white
      cases than in noncases, but the difference was not statistically significant
      (P:=0.066). Weighted proportional hazards regression analysis after adjustment
      for age, sex, and other CHD risk factors showed that having the V allele
      increased risk of CHD by 6.1-fold (risk ratio 6.1, 95% CI 1.7 to 22.9) in blacks
      but did not significantly increase the risk in whites. CONCLUSIONS: The TM A455V
      polymorphism predicts risk of developing CHD in blacks.

PMID- 11245642
TI  - Enhanced progression of early carotid atherosclerosis is related to Chlamydia
      pneumoniae (Taiwan acute respiratory) seropositivity.
AB  - BACKGROUND: Chlamydia pneumoniae (Cp) infection has been associated with
      atherosclerosis and has been proposed as a possible additional cardiovascular
      risk factor. However, the relationship between Cp seropositivity and the
      progression of early carotid atherosclerosis is not unequivocally clarified.
      METHODS AND RESULTS: We evaluated the association between serological detection
      of Cp IgG and/or IgA antibodies and the progression of the intima-media thickness
      (IMT) of the common carotid artery using duplex ultrasonography in a prospective
      study with a follow-up of 3 years in 272 consecutive patients with
      cerebrovascular disease. Cp-seropositive patients showed a significantly enhanced
      progression of the IMT even after adjustment for other cardiovascular risk
      factors (0.12 mm/y [95% CI 0.11 to 0.14] versus 0.07 mm/y [0.05 to 0.09];
      P:<0.005). Patients with increased C-reactive protein (>/=0.5 mg/dL) and Cp
      seropositivity showed the most pronounced IMT progression. Multivariate
      regression analysis revealed Cp seropositivity to be an independent risk factor
      for progression of early carotid atherosclerosis. Cox proportional-hazard
      regression analysis demonstrated a significantly increased rate of
      cerebrovascular and cardiovascular events in patients with Cp seropositivity,
      particularly in patients with increased C-reactive protein levels. CONCLUSIONS:
      Our data support the importance of chronic inflammation and infection for the
      early stages of atherosclerotic development.

PMID- 11245643
TI  - Gene expression profiling of human stent-induced neointima by cDNA array analysis
      of microscopic specimens retrieved by helix cutter atherectomy: Detection of
      FK506-binding protein 12 upregulation.
AB  - BACKGROUND: Restenosis due to neointima formation is the major limitation of
      stent-supported balloon angioplasty. Despite abundant animal data, molecular
      mechanisms of neointima formation have been investigated on only a limited basis
      in patients. This study sought to establish a method for profiling gene
      expression in human in-stent neointima and to identify differentially expressed
      genes that may serve as novel therapeutic targets. METHODS AND RESULTS: We
      retrieved tissue specimens from patients with symptomatic in-stent restenosis
      using a novel helix cutter atherectomy device. cDNA samples prepared from
      neointima (n=10) and, as a control, from the media of normal arteries (n=14) were
      amplified using a novel polymerase chain reaction protocol and hybridized to cDNA
      arrays. Immunohistochemistry characterized the atherectomy material as neointima.
      cDNA arrays readily identified differentially expressed genes. Some of the
      differentially expressed genes complied with expected gene expression patterns of
      neointima, including downregulation of desmin and upregulation of thrombospondin
      1, cyclooxygenase-1, and the 70-kDa heat shock protein B. Additionally, we
      discovered previously unknown gene expression patterns, such as downregulation of
      mammary-derived growth inhibitor and upregulation of FK506-binding protein 12
      (FKBP12). Upregulation of FKBP12 was confirmed at the protein level in neointimal
      smooth muscle cells. CONCLUSIONS: Gene expression patterns of human neointima
      retrieved by helix-cutter atherectomy can be reliably analyzed by cDNA array
      technology. This technique can identify therapeutic targets in patients, as
      exemplified by the findings regarding FKBP12. FKBP12 is the receptor for
      Rapamycin (sirolimus), which in animal models reduced neointima formation. Our
      study thus yields a rationale for the use of Rapamycin to prevent restenosis in
      patients.

PMID- 11245644
TI  - Ticlopidine pretreatment before coronary stenting is associated with sustained
      decrease in adverse cardiac events: data from the Evaluation of Platelet IIb/IIIa
      Inhibitor for Stenting (EPISTENT) Trial.
AB  - BACKGROUND: Platelet inhibition at the time of a percutaneous coronary
      intervention has consistently been shown to decrease the risk of thrombotic
      adverse events but not restenosis. The role of enhanced antiplatelet protection
      through pretreatment with the platelet ADP-receptor antagonist ticlopidine in
      preventing both the early and late complications of coronary stenting has not
      previously been explored. METHODS AND RESULTS: In the Evaluation of Platelet
      IIb/IIIa Inhibitor for Stenting (EPISTENT) trial, approximately 1600 patients
      were randomized to stenting with either placebo or abciximab in addition to
      aspirin and heparin. All stented patients also received ticlopidine after the
      procedure, but 58% of these patients were given ticlopidine before stenting at
      the discretion of the investigating physician. Among patients randomized to
      placebo, ticlopidine pretreatment was associated with a significant decrease in
      the incidence of the composite end point of death, myocardial infarction, or
      target vessel revascularization (TVR) at 1 year (adjusted hazard ratio, 0.73; 95%
      CI, 0.54 to 0.98; P:=0.036). Ticlopidine pretreatment did not significantly
      influence the risk of death or myocardial infarction in patients randomized to
      abciximab. Controlling for patient characteristics and for the propensity of
      being on ticlopidine, Cox proportional hazards regression identified ticlopidine
      pretreatment as an independent predictor of the need for TVR at 1 year (hazard
      ratio, 0.62; 95% CI, 0.43 to 0.89; P:=0.010) in both placebo-treated and
      abciximab-treated patients. CONCLUSIONS: In the EPISTENT trial, among patients
      randomized to stenting, starting ticlopidine before the percutaneous coronary
      intervention was associated with a significant decrease in the incidence of the
      12-month composite end point for patients not receiving abciximab and the need
      for TVR among all patients.

PMID- 11245645
TI  - Polycystic ovary syndrome is associated with endothelial dysfunction.
AB  - BACKGROUND: We recently reported endothelial dysfunction as a novel
      cardiovascular risk factor associated with insulin resistance/obesity. Here, we
      tested whether hyperandrogenic insulin-resistant women with polycystic ovary
      syndrome (PCOS) who are at increased risk of macrovascular disease display
      impaired endothelium-dependent vasodilation and whether endothelial function in
      PCOS is associated with particular metabolic and/or hormonal characteristics.
      METHODS AND RESULTS: We studied leg blood flow (LBF) responses to graded
      intrafemoral artery infusions of the endothelium-dependent vasodilator
      methacholine chloride (MCh) and to euglycemic hyperinsulinemia in 12 obese women
      with PCOS and in 13 healthy age- and weight-matched control subjects (OBW). LBF
      increments in response to MCh were 50% lower in the PCOS group than in the OBW
      group (P:<0.01). Euglycemic hyperinsulinemia increased LBF above baseline by 30%
      in the PCOS and 60% in OBW group (P:<0.05 between groups). Across all subjects,
      the maximal LBF response to MCh exhibited a strong inverse correlation with free
      testosterone levels (r=-0.52, P:<0.007). This relationship was stronger than with
      any other parameter, including insulin sensitivity. CONCLUSIONS: PCOS is
      characterized by (1) endothelial dysfunction and (2) resistance to the
      vasodilating action of insulin. This endothelial dysfunction appears to be
      associated with both elevated androgen levels and insulin resistance. Given the
      central vasoprotective role of endothelium, these findings could explain, at
      least in part, the increased risk for macrovascular disease in women with PCOS.

PMID- 11245646
TI  - Cost-effectiveness of the implantable cardioverter-defibrillator: results from
      the Canadian Implantable Defibrillator Study (CIDS).
AB  - BACKGROUND: In the Canadian Implantable Defibrillator Study (CIDS), we assessed
      the cost-effectiveness of the implantable cardioverter-defibrillator (ICD) in
      reducing the risk of death in survivors of previous ventricular tachycardia (VT)
      or fibrillation (VF). METHODS AND RESULTS: Healthcare resource use was collected
      prospectively on the first 430 patients enrolled in CIDS (n=212 ICD, n=218
      amiodarone). Mean cost per patient, adjusted for censoring, was computed for each
      group based on initial therapy assignment. Incremental cost-effectiveness of ICD
      therapy was computed as the ratio of the difference in cost (ICD minus
      amiodarone) to the difference in life expectancy (both discounted at 3% per
      year). All costs are in 1999 Canadian dollars (C$1 approximately US$0.65). Over
      6.3 years, mean cost per patient in the ICD group was C$87 715 versus C$38 600 in
      the amiodarone group (difference C$49 115; 95% CI C$25 502 to C$69 508). Life
      expectancy for the ICD group was 4.58 years versus 4.35 years for amiodarone
      (difference 0.23, 95% CI -0.09 to 0.55), for incremental cost-effectiveness of
      ICD therapy of C$213 543 per life-year gained. ICD benefit was greater in
      patients with low left ventricular ejection fraction (<35%), and cost
      effectiveness in this group was more attractive (C$108 484). Alternative
      extrapolations of survival benefit and costs to 12 years indicated cost
      effectiveness in the range of C$100 000 to C$150 000 per life-year gained.
      CONCLUSIONS: At C$213 543, the value for the money offered by ICD therapy is not
      attractive by currently accepted standards. Further research is warranted to
      identify the indications and patient subgroups for whom ICDs are a cost-effective
      use of resources.

PMID- 11245647
TI  - Qtc interval as a guide to select those patients with congestive heart failure
      and reduced left ventricular systolic function who will benefit from
      antiarrhythmic treatment with dofetilide.
AB  - BACKGROUND: A prolonged QTc interval is considered a contraindication for class
      III antiarrhythmic drugs, but the influence of a normal or a slightly increased
      baseline QTc interval on the risk or benefit of treatment with a class III
      antiarrhythmic drug is not sufficiently clarified. METHODS AND RESULTS: This
      prospectively defined substudy included 703 patients enrolled in the Danish
      Investigations of Arrhythmia and Mortality on Dofetilide-Congestive Heart Failure
      (DIAMOND-CHF) study. Patients included had moderate to severe CHF and reduced
      left ventricular systolic function. Baseline QTc interval was measured before
      randomization to either dofetilide, a new class III antiarrhythmic drug, or
      placebo. During a median follow-up of 18 months (minimum 1 year), 285 patients
      (41%) died. Baseline QTc interval had no prognostic value on survival in placebo
      treated patients. In dofetilide-treated patients, a baseline QTc interval <429 ms
      was associated with a significant risk reduction (risk ratio 0.4, 95% CI 0.3 to
      0.8). With increasing QTc interval, the risk increased gradually, and for QTc
      interval >479 ms, risk ratio was 1.3 (0.8 to 1.9). CONCLUSIONS: A baseline QTc
      interval within normal limits is associated with a marked reduction of mortality
      in patients with CHF and left ventricular systolic dysfunction treated with
      dofetilide. This is a potentially important indication of which patients with CHF
      might benefit from prophylactic treatment with an antiarrhythmic drug.

PMID- 11245649
TI  - Catheter ablation of typical atrial flutter: a randomized comparison of 2 methods
      for determining complete bidirectional isthmus block.
AB  - BACKGROUND: Complete bidirectional isthmus conduction block (CBIB) was initially
      assessed by sequential detailed activation mapping at both sides of the ablation
      line during proximal coronary sinus and anteroinferior right atrium pacing.
      Mapping only the ablation line ("on-site" atrial potential analysis) was recently
      reported as a means of CBIB identification. The study was designed to compare
      these 2 techniques prospectively regarding the diagnosis of CBIB. METHODS AND
      RESULTS: In 76 consecutive patients (mean age, 63.4+/-10.5 years), typical atrial
      flutter ablation was performed using either the activation mapping technique
      (group I) or on-site atrial potential analysis (group II). Criteria for CBIB
      using on-site atrial potential analysis was the recording of parallel, widely
      spaced double atrial potentials along the ablation line. The CBIB criterion was
      retrospectively searched using the alternative technique at the end of the
      procedure. In successful patients, the mean radiofrequency delivery duration was
      longer in group II (845+/-776 versus 534+/-363 s; P:=0.03). On-site, clear-cut,
      widely spaced double atrial potentials and activation mapping suggesting CBIB
      were concomitantly observed in only 47 patients (54%), and ambiguous/atypical
      double potentials were recorded in 31 patients (39%). CONCLUSIONS: Although
      feasible, the on-site atrial potential analysis seemed to be inferior to the
      classic activation mapping technique, mainly because of the ambiguity of
      electrogram interpretation along the ablation line. However, when combined with
      the activation mapping technique, it provided additional information regarding
      isthmus conduction properties in some cases. Therefore, optimally, both methods
      should be used concomitantly.

PMID- 11245648
TI  - Heart rate and cardiac rhythm relationships with bisoprolol benefit in chronic
      heart failure in CIBIS II Trial.
AB  - BACKGROUND: beta-Blockade-induced benefit in heart failure (HF) could be related
      to baseline heart rate and treatment-induced heart rate reduction, but no such
      relationships have been demonstrated. METHODS AND RESULTS: In CIBIS II, we
      studied the relationships between baseline heart rate (BHR), heart rate changes
      at 2 months (HRC), nature of cardiac rhythm (sinus rhythm or atrial
      fibrillation), and outcomes (mortality and hospitalization for HF). Multivariate
      analysis of CIBIS II showed that in addition to beta-blocker treatment, BHR and
      HRC were both significantly related to survival and hospitalization for worsening
      HF, the lowest BHR and the greatest HRC being associated with best survival and
      reduction of hospital admissions. No interaction between the 3 variables was
      observed, meaning that on one hand, HRC-related improvement in survival was
      similar at all levels of BHR, and on the other hand, bisoprolol-induced benefit
      over placebo for survival was observed to a similar extent at any level of both
      BHR and HRC. Bisoprolol reduced mortality in patients with sinus rhythm (relative
      risk 0.58, P:<0.001) but not in patients with atrial fibrillation (relative risk
      1.16, P:=NS). A similar result was observed for cardiovascular mortality and
      hospitalization for HF worsening. CONCLUSIONS: BHR and HRC are significantly
      related to prognosis in heart failure. beta-Blockade with bisoprolol further
      improves survival at any level of BHR and HRC and to a similar extent. The
      benefit of bisoprolol is questionable, however, in patients with atrial
      fibrillation.

PMID- 11245650
TI  - Lysophosphatidylcholine and reactive oxygen species mediate the synergistic
      effect of mildly oxidized LDL with serotonin on vascular smooth muscle cell
      proliferation.
AB  - BACKGROUND: Mild oxidation of LDL enhances its atherogenic potential and induces
      a synergistic interaction with serotonin (5HT) on vascular smooth muscle cell
      (VSMC) proliferation. Because of its complex chemical nature, the mitogenic
      components of mildly oxidized LDL (moxLDL) remain unclear. METHODS AND RESULTS:
      We examined both the effects of lysophosphatidylcholine (LPC) and hydrogen
      peroxide (H(2)O(2)), a donor of reactive oxygen species, as major components of
      moxLDL and their interactions with 5HT on VSMC proliferation. Growth-arrested
      VSMCs were incubated with different concentrations of moxLDL, LPC, H(2)O(2), or
      LPC with H(2)O(2) in the absence or presence of 5HT. DNA synthesis in VSMCs was
      examined by [(3)H]thymidine incorporation. MoxLDL, LPC, H(2)O(2), and 5HT
      stimulated DNA synthesis in a dose-dependent manner. MoxLDL had a maximal
      stimulatory effect at a concentration of 5 microg/mL (211%), LPC at 15 micromol/L
      (156%), H(2)O(2) at 5 micromol/L (179%), and 5HT at 50 micromol/L (205%). Added
      together, moxLDL (50 ng/mL) and 5HT (50 micromol/L) synergistically increased DNA
      synthesis (443%). Coincubation of LPC (1 micromol/L) with H(2)O(2) (0.5
      micromol/L) and 5HT (5 micromol/L) resulted in a synergistic increase in DNA
      synthesis (439%), which was nearly equal to that of moxLDL with 5HT (443%). The
      combined effects of LPC, H(2)O(2), and 5HT on DNA synthesis were completely
      reversed by the combined use of an antioxidant, N:-acetylcysteine (400
      micromol/L) or butylated hydroxytoluene (20 micromol/L), with a 5HT(2) receptor
      antagonist, LY281067 (10 microg/mL). CONCLUSIONS: Our results suggest that both
      LPC and reactive oxygen species may contribute to the mitogenic effect of moxLDL
      on VSMCs and its synergistic effect with 5HT.

PMID- 11245651
TI  - Ribozyme-mediated inhibition of rat leukocyte-type 12-lipoxygenase prevents
      intimal hyperplasia in balloon-injured rat carotid arteries.
AB  - BACKGROUND: 12-Lipoxygenase (12-LO) products of arachidonate metabolism have
      growth and chemotactic effects in vascular smooth muscle cells. We have also
      recently demonstrated increased 12-LO mRNA and protein expression in the
      neointima of balloon-injured rat carotid arteries. In this study, we evaluated
      whether 12-LO activation plays a role in neointimal thickening in this rat model
      by using a specific ribozyme (Rz) directed to rat 12-LO. METHODS AND RESULTS: We
      designed a chimeric DNA-RNA hammerhead Rz to cleave rat leukocyte-type 12-LO
      mRNA. This Rz dose-dependently cleaved a 166-nucleotide target 12-LO mRNA
      substrate in vitro and reduced 12-LO mRNA and protein expression in rat vascular
      smooth muscle cells. A control mutant Rz (MRz) with a point mutation in the
      catalytic site was inactive. To test the in vivo efficacy of the 12-LO Rz, the
      left common carotid arteries of rats were injured with a balloon catheter. The
      distal half of the injured arteries was treated with Rz or MRz mixed with
      lipofectin. The proximal half received only lipofectin. Twelve days after injury,
      intima-to-media ratios were significantly lower in the Rz-treated sections than
      in untreated sections from the same rat (0.742+/-0.16 versus 1.749+/-0.12,
      P:<0.001). In contrast, the MRz had no significant effect. CONCLUSIONS: These
      results indicate the important role of the leukocyte-type 12-LO pathway in
      restenosis in response to injury.

PMID- 11245652
TI  - Cardiac overexpression of a G(q) inhibitor blocks induction of extracellular
      signal-regulated kinase and c-Jun NH(2)-terminal kinase activity in in vivo
      pressure overload.
AB  - BACKGROUND: Understanding the cellular signals that initiate cardiac hypertrophy
      is of critical importance in identifying the pathways that mediate heart failure.
      The family of mitogen-activated protein kinases (MAPKs), including the
      extracellular signal-regulated kinases (ERKs), c-Jun NH(2)-terminal kinase (JNK),
      and p38 MAPKs, may play specific roles in myocardial growth and function. METHODS
      AND RESULTS: To determine the mechanism of activation of MAPK pathways during the
      development of cardiac hypertrophy, we evaluated the induction of MAPK activity
      after aortic constriction in wild-type and in 2 types of cardiac gene-targeted
      mice: one overexpressing a carboxyl-terminal peptide of Galpha(q) that inhibits
      G(q)-mediated signaling (TG GqI mouse) and another overexpressing a carboxyl
      terminal peptide of beta-adrenergic receptor kinase-1 that inhibits Gbetagamma
      signaling (TG betaARKct mouse). Wild-type mice with pressure overload showed an
      acute induction of JNK, followed by the induction of p38/p38beta at 3 days and
      ERK at 7 days. Both JNK and p38 activity remained elevated at 7 days after
      banding. In TG GqI mice, hypertrophy was significantly attenuated, and induction
      of ERK and JNK activity was abolished, whereas the induction of p38 and p38beta
      was robust, but delayed. By contrast, all 3 MAPK pathways were activated by
      aortic constriction in the TG betaARKct hearts, suggesting a role for Galpha(q),
      but not Gbetagamma. CONCLUSIONS: Taken together, these data show that the
      induction of ERK and JNK activity in in vivo pressure-overload hypertrophy is
      mediated through the stimulation of G(q)-coupled receptors and that non-G(q)
      mediated pathways are recruited to activate p38 and p38beta.

PMID- 11245653
TI  - Regulation of cardiomyocyte mechanotransduction by the cardiac cycle.
AB  - BACKGROUND: Overloading the left ventricle in systole (pressure overload) is
      associated with a distinct morphological response compared with overload in
      diastole (volume overload). METHODS AND RESULTS: We designed a novel computer
      controlled experimental system that interfaces biaxially uniform strain with
      electrical pacing, so that cellular deformation can be imposed during a specified
      phase of the cardiac cycle. Cardiomyocytes were exposed to strain (4%) during
      either the first third (systolic phase) or last third (diastolic phase) of the
      cardiac cycle. Strain imposed during the systolic phase selectively activated
      p44/42 mitogen-activated protein kinase (MAPK) and MAPK/extracellular signal
      regulated protein kinase kinase (MEK1/2, an activator of p44/42 MAPK) compared
      with strain imposed during the diastolic phase. In contrast, there was no
      difference in activation of p38 and c-Jun NH(2)-terminal kinases induced by
      strain imposed during the systolic phase (5.8- and 3.3-fold versus control, n=4)
      compared with the diastolic phase (5.5- and 3.1-fold). Induction of both brain
      natriuretic peptide (5.8-fold versus control, P:<0.05, n=3) and tenascin-C (7.0
      fold, P:<0.02) mRNA expression by strain imposed during the systolic phase was
      greater than during the diastolic phase (3.9- and 3.6-fold, respectively).
      [(3)H]leucine incorporation induced by strain imposed during the systolic phase
      (4.0-fold versus control) was greater than during the diastolic phase (2.7-fold,
      P:<0.02, n=4); a selective inhibitor of MEK1/2 inhibited this difference.
      CONCLUSIONS: Mechanical activation of p44/42 MAPK and MEK1/2, gene expression,
      and protein synthesis is regulated by the cardiac cycle, suggesting that
      mechanotransduction at the cellular level may underlie differences between
      pressure and volume overload of the heart.

PMID- 11245654
TI  - Increased wave break during ventricular fibrillation in the epicardial border
      zone of hearts with healed myocardial infarction.
AB  - BACKGROUND: The action potential duration (APD) restitution hypothesis of wave
      break during ventricular fibrillation (VF) in the epicardial border zone (EBZ) of
      hearts with chronic myocardial infarction is unknown. METHODS AND RESULTS: VF was
      induced by rapid pacing, and the EBZ with the two adjoining sites (right
      ventricle and lateral left ventricle) were sequentially mapped in random order in
      7 open-chest anesthetized dogs 6 to 8 weeks after left anterior descending artery
      occlusion and in 4 control dogs. At each site, 3 seconds of VF was mapped with
      477 bipolar electrodes 1.6 mm apart. The number of wave fronts and approximate
      entropy were significantly (P:<0.01) higher in the EBZ than all other sites in
      both groups independent of the rate of invasion of new wave fronts and epicardial
      breakthroughs. The higher wavelet density in the EBZ was caused by increased
      (P:<0.01) incidence of spontaneous wave breaks. There was no difference between
      the two groups in either reentry period (80 episodes) or VF cycle length. Reentry
      in the EBZ had a smaller core perimeter, slower rotational speed, and a small or
      no excitable gap (P:<0.01), often causing termination after one rotation. The
      dynamic monophasic action potential duration restitution curve in the EBZ had
      longer (P:<0.01) diastolic intervals, over which the slope was >1. Connexin43
      positive staining was significantly (P:<0.01) and selectively reduced in the EBZ.
      CONCLUSIONS: A selective increase in wave break and alteration of reentry occur
      in the EBZ during VF in hearts with healed myocardial infarction. Increased wave
      break in the EBZ is compatible with the action potential duration restitution
      hypothesis.

PMID- 11245655
TI  - Improvement of defibrillation efficacy and quantification of activation patterns
      during ventricular fibrillation in a canine heart failure model.
AB  - BACKGROUND: Little is known about the effects of heart failure (HF) on the
      defibrillation threshold (DFT) and the characteristics of activation during
      ventricular fibrillation (VF). METHODS AND RESULTS: HF was induced by rapid right
      ventricular (RV) pacing for at least 3 weeks in 6 dogs. Another 6 dogs served as
      controls. Catheter defibrillation electrodes were placed in the RV apex, the
      superior vena cava, and the great cardiac vein (CV). An active can coupled to the
      superior vena cava electrode served as the return for the RV and CV electrodes.
      DFTs were determined before and during HF for a shock through the RV electrode
      with and without a smaller auxiliary shock through the CV electrode. VF
      activation patterns were recorded in HF and control animals from 21x24 unipolar
      electrodes spaced 2 mm apart on the ventricular epicardium. Using these
      recordings, we computed a number of quantitative VF descriptors. DFT was
      unchanged in the control dogs. DFT energy was increased 79% and 180% (with and
      without auxiliary shock, respectively) in HF compared with control dogs. During
      but not before HF, DFT energy was significantly lowered (21%) by addition of the
      auxiliary shock. The VF descriptors revealed marked VF differences between HF and
      control dogs. The differences suggest decreased excitability and an increased
      refractory period during HF. Most, but not all, descriptors indicate that VF was
      less complex during HF, suggesting that VF complexity is multifactorial and
      cannot be expressed by a scalar quantity. CONCLUSIONS: HF increases the DFT. This
      is partially reversed by an auxiliary shock. HF markedly changes VF activation
      patterns.

PMID- 11245656
TI  - Recombinant hirudin in clinical practice: focus on lepirudin.
AB  - Clinical applications for recombinant hirudins have been investigated for the
      past 10 years. The first indication for which a hirudin-lepirudin-has been
      approved is treatment of heparin-induced thrombocytopenia (HIT). Also, the
      recently completed trials for use of lepirudin in unstable angina indicate a
      potentially new indication. This review describes pharmacology and clinical
      applications of lepirudin with an emphasis on HIT and unstable angina. An
      overview of usage of lepirudin in acute coronary syndromes is given, as well as a
      summary of rare indications for lepirudin, such as extracorporeal circulation,
      for which comprehensive data are lacking.

PMID- 11245657
TI  - Ventricular lipoma detection by magnetic resonance imaging.

PMID- 11245658
TI  - Multiple cardiac tumors in the fetus.

PMID- 11245659
TI  - Percutaneous closure of patent foramen ovale in patients with paradoxical
      embolism.

PMID- 11245660
TI  - L-arginine and nitric oxide: an inseparable couple?

PMID- 11245661
TI  - Effects of intravenous and intracoronary adenosine 5'-triphosphate as compared
      with adenosine on coronary flow and pressure dynamics.

PMID- 11245662
TI  - Tissue factor overexpression in rat arterial neointima models: thrombosis and
      progression of advanced atherosclerosis.

PMID- 11245663
TI  - Electron-beam computed tomography in the assessment of coronary artery disease
      after heart transplantation.

PMID- 11245664
TI  - Trauma centers bleeding dollars with balance sheets in the red.

PMID- 11245665
TI  - Estrogen prevents the lipopolysaccharide-induced inflammatory response in
      microglia.
AB  - After neuronal injury and in several neurodegenerative diseases, activated
      microglia secrete proinflammatory molecules that can contribute to the
      progressive neural damage. The recent demonstration of a protective role of
      estrogen in neurodegenerative disorders in humans and experimental animal models
      led us to investigate whether this hormone regulates the inflammatory response in
      the CNS. We here show that estrogen exerts an anti-inflammatory activity on
      primary cultures of rat microglia, as suggested by the blockage of the phenotypic
      conversion associated with activation and by the prevention of lipopolysaccharide
      induced production of inflammatory mediators: inducible form of NO synthase
      (iNOS), prostaglandin-E(2) (PGE(2)), and metalloproteinase-9 (MMP-9). These
      effects are dose-dependent, maximal at 1 nm 17beta-estradiol, and can be blocked
      by the estrogen receptor (ER) antagonist ICI 182,780. The demonstration of
      ERalpha and ERbeta expression in microglia and macrophages and the observation of
      estrogen blockade of MMP-9 mRNA accumulation and MMP-9 promoter induction further
      support the hypothesis of a genomic activity of estrogen via intracellular
      receptors. This is the first report showing an anti-inflammatory activity of
      estrogen in microglia. Our study proposes a novel explanation for the protective
      effects of estrogen in neurodegenerative and inflammatory diseases and provides
      new molecular and cellular targets for the screening of ER ligands acting in the
      CNS.

PMID- 11245666
TI  - Chronic exposure to nicotine upregulates the human (alpha)4((beta)2 nicotinic
      acetylcholine receptor function.
AB  - Widely expressed in the brain, the alpha4beta2 nicotinic acetylcholine receptor
      (nAChR) is proposed to play a major role in the mechanisms that lead to and
      maintain nicotine addiction. Using the patch-clamp technique and pharmacological
      protocols, we examined the consequences of long-term exposure to 0.1-10
      micrometer nicotine in K-177 cells expressing the major human brain alpha4beta2
      receptor. The acetylcholine dose-response curves are biphasic and revealed both a
      high- and a low-affinity component with apparent EC(50) values of 1.6 and 62
      micrometer. Ratios of receptors in the high- and low-affinity components are 25
      and 75%, respectively. Chronic exposure to nicotine or nicotinic antagonists
      [dihydro-beta-erytroidine (DHbetaE) or methyllycaconitine (MLA)] increases the
      fraction of high-affinity receptors up to 70%. Upregulated acetylcholine-evoked
      currents increase by twofold or more and are less sensitive to desensitization.
      Functional upregulation is independent of protein synthesis as shown by the lack
      of effect of 20 micrometer cycloheximide. Single-channel currents recorded with
      100 nm acetylcholine show predominantly high conductances (38.8 and 43.4 pS),
      whereas additional smaller conductances (16.7 and 23.5 pS) were observed with 30
      micrometer acetylcholine. In addition, long-term exposure to dihydro-beta
      erytroidine increases up to three times the frequency of channel openings. These
      data indicate, in contrast to previous studies, that human alpha4beta2 nAChRs are
      functionally upregulated by chronic nicotine exposure.

PMID- 11245667
TI  - Tissue-specific proteolysis of Huntingtin (htt) in human brain: evidence of
      enhanced levels of N- and C-terminal htt fragments in Huntington's disease
      striatum.
AB  - Proteolysis of mutant huntingtin (htt) has been hypothesized to occur in
      Huntington's disease (HD) brains. Therefore, this in vivo study examined htt
      fragments in cortex and striatum of adult HD and control human brains by Western
      blots, using domain-specific anti-htt antibodies that recognize N- and C-terminal
      domains of htt (residues 181-810 and 2146-2541, respectively), as well as the 17
      residues at the N terminus of htt. On the basis of the patterns of htt fragments
      observed, different "protease-susceptible domains" were identified for
      proteolysis of htt in cortex compared with striatum, suggesting that htt
      undergoes tissue-specific proteolysis. In cortex, htt proteolysis occurs within
      two different N-terminal domains, termed protease-susceptible domains "A" and
      "B." However, in striatum, a different pattern of fragments indicated that
      proteolysis of striatal htt occurred within a C-terminal domain termed "C," as
      well as within the N-terminal domain region designated "A". Importantly, striatum
      from HD brains showed elevated levels of 40-50 kDa N-terminal and 30-50 kDa C
      terminal fragments compared with that of controls. Increased levels of these htt
      fragments may occur from a combination of enhanced production or retarded
      degradation of fragments. Results also demonstrated tissue-specific
      ubiquitination of certain htt N-terminal fragments in striatum compared with
      cortex. Moreover, expansions of the triplet-repeat domain of the IT15 gene
      encoding htt was confirmed for the HD tissue samples studied. Thus, regulated
      tissue-specific proteolysis and ubiquitination of htt occur in human HD brains.
      These results suggest that the role of huntingtin proteolysis should be explored
      in the pathogenic mechanisms of HD.

PMID- 11245668
TI  - Differential subcellular localization of mGluR1a and mGluR5 in the rat and monkey
      Substantia nigra.
AB  - Neurons in the rat substantia nigra (SN) are enriched in group I metabotropic
      glutamate receptor (mGluR) subtypes and respond to group I mGluR activation. To
      better understand the mechanisms by which mGluR1 and mGluR5 mediate these
      effects, the goal of this study was to elucidate the subsynaptic localization of
      these two receptor subtypes in the rat and monkey substantia nigra. At the light
      microscope level, neurons of the SN pars reticulata (SNr) displayed moderate to
      strong immunoreactivity for both mGluR1a and mGluR5 in rats and monkeys. However,
      mGluR1a labeling was much stronger in monkey than in rat SN pars compacta (SNc)
      neurons, whereas a moderate level of mGluR5 immunoreactivity was found in both
      species. At the electron microscope level, the immunoreactivity for both group I
      mGluR subtypes was primarily expressed postsynaptically, although light mGluR1a
      labeling was occasionally seen in axon terminals in the rat SNr. Immunogold
      studies revealed a striking difference in the subcellular distribution of mGluR1a
      and mGluR5 immunoreactivity in SNr and SNc neurons. Although the bulk of mGluR1a
      was attached to the plasma membrane, >80% of mGluR5 immunoreactivity was
      intracellular. Plasma membrane-bound immunoreactivity for group I mGluRs in both
      SNc and SNr neurons was mostly extrasynaptic or in the main body of symmetric,
      putative GABAergic synapses. On the other hand, asymmetric synapses either were
      nonimmunoreactive or displayed perisynaptic labeling. These data raise important
      questions about the trafficking, internalization, and potential functions of
      group I mGluRs at extrasynaptic sites or symmetric synapses in the substantia
      nigra.

PMID- 11245669
TI  - Subunit-dependent modulation of neuronal nicotinic receptors by zinc.
AB  - We examined the effect of zinc on rat neuronal nicotinic acetylcholine receptors
      (nAChRs) expressed in Xenopus oocytes as simple heteromers of alpha2, alpha3, or
      alpha4 and beta2 or beta4. Coapplication of zinc with low concentrations of
      acetylcholine (</=EC(10)) resulted in differential effects depending on receptor
      subunit composition. The alpha2beta2, alpha2beta4, alpha3beta4, alpha4beta2, and
      alpha4beta4 receptors exhibited biphasic modulation by zinc, with potentiation of
      the acetylcholine response occurring at 1-100 micrometer zinc and inhibition
      occurring at higher zinc concentrations. In contrast, alpha3beta2 receptors were
      only inhibited by zinc (IC(50) = 97 +/- 16 micrometer). The greatest potentiating
      effect of zinc was seen with alpha4beta4 receptors that were potentiated to 560
      +/- 17% of the response to ACh alone, with an EC(50) of 22 +/- 4 micrometer zinc.
      Cadmium, but not nickel, was also able to potentiate alpha4beta4 receptors. Both
      zinc potentiation of alpha4beta4 receptors and zinc inhibition of alpha3beta2
      receptors were voltage independent. The sensitivity of zinc potentiation of
      alpha4beta4 to diethylpyrocarbonate treatment and alterations in pH suggested the
      involvement of histidine residues. Zinc continued to inhibit alpha4beta4 and
      alpha3beta2 after diethylpyrocarbonate treatment. Application of a potentiating
      zinc concentration increased the response of alpha4beta2 and alpha4beta4
      receptors to saturating ACh concentrations. The rate of Ach-induced
      desensitization of these receptors was unaffected by zinc. Our results reveal
      zinc potentiation as a new mode of neuronal nAChR modulation.

PMID- 11245670
TI  - Minimizing synaptic depression by control of release probability.
AB  - Transmission at the end-bulb synapse formed by auditory nerve terminals onto the
      soma of neurons in the avian nucleus magnocellularis is characterized by high
      transmitter release probability and strong synaptic depression. Activation of
      presynaptic GABA(B) receptors minimizes depression at this synapse and
      significantly enhances synaptic strength during high-frequency activity. Here we
      investigate synaptic mechanisms underlying this phenomenon. EPSC amplitudes
      evoked by 200 Hz trains increased more than twofold when release probability was
      reduced with Cd(2+) or baclofen. This effect was not exhibited by a transmitter
      depletion model of presynaptic depression, which predicts that EPSC amplitudes
      reach a common steady-state amplitude during high-frequency trains, despite
      alterations of initial release probability. However, an additional source of
      postsynaptic depression was sufficient to explain our findings. Aniracetam, a
      modulator of AMPA receptors that reduces desensitization, decreased the amount of
      synaptic depression during trains, indicating that desensitization occurred
      during trains of stimuli. However, this effect of aniracetam was absent when
      release probability was lowered with baclofen or Cd(2+). No effect of aniracetam
      on the NMDA component of the EPSC was seen, confirming a postsynaptic site of
      action of aniracetam. When desensitization was reduced with aniracetam, steady
      state EPSC amplitudes during trains were found to converge over a wide range of
      release probabilities, as predicted by the depletion model. Additional evidence
      of AMPA receptor desensitization was provided by direct measurement of quantal
      amplitudes immediately after stimulus trains. Thus, presynaptic modulation by
      GABA(B) receptors regulates the extent of AMPA receptor desensitization and
      controls synaptic strength, thereby modulating the flow of information at an
      auditory synapse.

PMID- 11245671
TI  - Upregulation of dorsal root ganglion (alpha)2(delta) calcium channel subunit and
      its correlation with allodynia in spinal nerve-injured rats.
AB  - Peripheral nerve injury can lead to a persistent neuropathic pain state in which
      innocuous tactile stimulation elicits pain behavior (tactile allodynia). Spinal
      administration of the anticonvulsant gabapentin suppresses allodynia by an
      unknown mechanism. In vitro studies indicate that gabapentin binds to the
      alpha(2)delta-1 (hereafter referred to as alpha(2)delta) subunit of voltage-gated
      calcium channels. We hypothesized that nerve injury may result in altered
      alpha(2)delta subunit expression in spinal cord and dorsal root ganglia (DRGs)
      and that this change may play a role in neuropathic pain processing. Using a rat
      neuropathic pain model in which gabapentin-sensitive tactile allodynia develops
      after tight ligation of the left fifth and sixth lumbar spinal nerves, we found a
      >17-fold, time-dependent increase in alpha(2)delta subunit expression in DRGs
      ipsilateral to the nerve injury. Marked alpha(2)delta subunit upregulation was
      also evident in rats with unilateral sciatic nerve crush, but not dorsal
      rhizotomy, indicating a peripheral origin of the expression regulation. The
      increased alpha(2)delta subunit expression preceded the allodynia onset and
      diminished in rats recovering from tactile allodynia. RNase protection
      experiments indicated that the DRG alpha(2)delta regulation was at the mRNA
      level. In contrast, calcium channel alpha(1B) and beta(3) subunit expression was
      not co-upregulated with the alpha(2)delta subunit after nerve injury. These data
      suggest that DRG alpha(2)delta regulation may play an unique role in
      neuroplasticity after peripheral nerve injury that may contribute to allodynia
      development.

PMID- 11245672
TI  - Antisense knockdown of the glial glutamate transporter GLT-1, but not the
      neuronal glutamate transporter EAAC1, exacerbates transient focal cerebral
      ischemia-induced neuronal damage in rat brain.
AB  - Transient focal cerebral ischemia leads to extensive neuronal damage in cerebral
      cortex and striatum. Normal functioning of glutamate transporters clears the
      synaptically released glutamate to prevent excitotoxic neuronal death. This study
      evaluated the functional role of the glial (GLT-1) and neuronal (EAAC1) glutamate
      transporters in mediating ischemic neuronal damage after transient middle
      cerebral artery occlusion (MCAO). Transient MCAO in rats infused with GLT-1
      antisense oligodeoxynucleotides (ODNs) led to increased infarct volume (45 +/-
      8%; p < 0.05), worsened neurological status, and increased mortality rate,
      compared with GLT-1 sense/random ODN-infused controls. Transient MCAO in rats
      infused with EAAC1 antisense ODNs had no significant effect on any of these
      parameters. This study suggests that GLT-1, but not EAAC1, knockdown exacerbates
      the neuronal death and thus neurological deficit after stroke.

PMID- 11245673
TI  - Recovery from inactivation of t-type ca2+ channels in rat thalamic neurons.
AB  - We studied the gating kinetics, especially the kinetics of recovery from
      inactivation, of T-type Ca(2+) channels (T-channels) in thalamic neurons. The
      recovery course is associated with no discernible Ca(2+) current and is
      characterized by an initial delay, as well as a subsequent exponential phase.
      These findings are qualitatively similar to previous observations on neuronal
      Na(+) channels and suggest that T-channels also must deactivate to recover from
      inactivation. In contrast to Na(+) channels in which both the delay and the time
      constant of the exponential phase are shortened with increasing
      hyperpolarization, in T-channels the time constant of the exponential recovery
      phase remains unchanged between -100 and -200 mV, although the initial delay is
      still shortened e-fold per 43 mV hyperpolarization over the same voltage range.
      The deactivating kinetics of tail T-currents also show a similar voltage
      dependence between -90 and -170 mV. According to the hinged-lid model of fast
      inactivation, these findings suggest that the affinity difference between
      inactivating peptide binding to the activated channel and binding to the fully
      deactivated channel is much smaller in T-channels than in Na(+) channels.
      Moreover, the inactivating peptide in T-channels seems to have much slower
      binding and unbinding kinetics, and the unbinding rates probably remain unchanged
      once the inactivated T-channel has gone through the initial steps of deactivation
      and "closes" the pore (with the activation gate). T-channels thus might have a
      more rigid hinge and a more abrupt conformational change in the inactivation
      machinery associated with opening and closing of the pore.

PMID- 11245674
TI  - Mitochondria control ampa/kainate receptor-induced cytoplasmic calcium
      deregulation in rat cerebellar granule cells.
AB  - Although mitochondria mediate the delayed failure of cytoplasmic Ca(2+)
      homeostasis [delayed Ca(2+) deregulation (DCD)] in rat cerebellar granule cells
      resulting from chronic activation of NMDA receptors, their role in AMPA/KA
      induced DCD remains to be established. The mitochondrial ATP synthase inhibitor
      oligomycin protected cells against KA- but not NMDA-evoked DCD. In contrast to
      NMDA-evoked DCD, no additional protection was afforded by the further addition of
      rotenone. The effects of KA on cytoplasmic Ca(2+) homeostasis, including the
      protection afforded by oligomycin, could be reproduced by veratridine. KA
      exposure induced a partial mitochondrial depolarization that was enhanced by
      oligomycin, indicating ATP synthase reversal. The nonglycolytic substrates
      pyruvate and lactate were unable to maintain Ca(2+) homeostasis in the presence
      of KA. In contrast to NMDA, KA exposure did not cause mitochondrial Ca(2+)
      loading. The data indicate that Na(+) entry via noninactivating AMPA/KA receptors
      or voltage-activated Na(+) channels compromises mitochondrial function
      sufficiently to cause ATP synthase reversal. Oligomycin may protect by preventing
      the consequent mitochondrial drain of cytoplasmic ATP.

PMID- 11245675
TI  - Insulin-like growth factor I (IGF-I) protects cells from apoptosis by Alzheimer's
      V642I mutant amyloid precursor protein through IGF-I receptor in an IGF-binding
      protein-sensitive manner.
AB  - It has been found that insulin-like growth factor I (IGF-I) exerts cytoprotection
      against Abeta amyloid-induced neuronal cell death. Deposits of Abeta amyloid are
      one of the pathological hallmarks of Alzheimer's disease (AD). Here, we examined
      whether IGF-I exerts protective activity against cell death induced by a familial
      AD (FAD)-linked mutant of amyloid precursor protein (APP), and we found that IGF
      I protected cells from toxicity of FAD-associated V642I mutant of APP in multiple
      cell systems. IGFBP-3 blocked this action of IGF-I, but not of des(1-3)IGF-I,
      which was as active as IGF-I in the presence of IGFBP-3. The data also
      demonstrated that the IGF-I receptor (IGF-IR) mediates the protective activity of
      IGF-I. The antagonizing function of the IGF-I/IGF-IR system against V642I-APP,
      which is further antagonized by IGFBP-3, provides a molecular clue to the
      understanding of AD pathophysiology and to the establishment of potential therapy
      for AD.

PMID- 11245676
TI  - Differential regulation of transmitter release by presynaptic and glial Ca2+
      internal stores at the neuromuscular synapse.
AB  - The differential regulation of synaptic transmission by internal Ca(2+) stores of
      presynaptic terminals and perisynaptic Schwann cells (PSCs) was studied at the
      frog neuromuscular junction. Thapsigargin (tg), an inhibitor of Ca(2+)-ATPase
      pumps of internal stores, caused a transient Ca(2+) elevation in PSCs, whereas it
      had no effect on Ca(2+) stores of presynaptic terminals at rest. Tg prolonged
      presynaptic Ca(2+) responses evoked by single action potentials with no
      detectable increase in the resting Ca(2+) level in nerve terminals. However,
      Ca(2+) accumulation was observed during high frequency stimulation. Tg induced a
      rapid rise in endplate potential (EPP) amplitude, accompanied by a delayed and
      transient increase. The effects appeared presynaptic, as suggested by the lack of
      effects of tg on the amplitude and time course of miniature EPPs (MEPPs).
      However, MEPP frequency was increased when preparations were stimulated tonically
      (0.2 Hz). The delayed and transient increase in EPP amplitude was occluded by
      injections of the Ca(2+) chelator BAPTA into PSCs before tg application, whereas
      a rise in intracellular Ca(2+) in PSCs induced by inositol 1,4,5-triphosphate
      (IP(3)) injections potentiated transmitter release. Furthermore, increased Ca(2+)
      buffering capacity after BAPTA injection in PSCs resulted in a more pronounced
      synaptic depression induced by high frequency stimulation of the motor nerve (10
      Hz/80 sec). It is concluded that presynaptic Ca(2+) stores act as a Ca(2+)
      clearance mechanism to limit the duration of transmitter release, whereas Ca(2+)
      release from glial stores initiates Ca(2+)-dependent potentiation of synaptic
      transmission.

PMID- 11245677
TI  - Traumatic axonal injury induces calcium influx modulated by tetrodotoxin
      sensitive sodium channels.
AB  - Diffuse axonal injury (DAI) is one of the most common and important pathologies
      resulting from the mechanical deformation of the brain during trauma. It has been
      hypothesized that calcium influx into axons plays a major role in the
      pathophysiology of DAI. However, there is little direct evidence to support this
      hypothesis, and mechanisms of potential calcium entry have not been explored. In
      the present study, we used an in vitro model of axonal stretch injury to evaluate
      the extent and modulation of calcium entry after trauma. Using a calcium
      sensitive dye, we observed a dramatic increase in intra-axonal calcium levels
      immediately after injury. Axonal injury in a calcium-free extracellular solution
      resulted in no change in calcium concentration, suggesting an extracellular
      source for the increased post-traumatic calcium levels. We also found that the
      post-traumatic change in intra-axonal calcium was completely abolished by the
      application of the sodium channel blocker tetrodotoxin or by replacement of
      sodium with N-methyl-d-glucamine. In addition, application of the voltage-gated
      calcium channel (VGCC) blocker omega-conotoxin MVIIC attenuated the post
      traumatic increase in calcium. Furthermore, blockade of the Na(+)-Ca(2+)
      exchanger with bepridil modestly reduced the calcium influx after injury. In
      contrast to previously proposed mechanisms of calcium entry after axonal trauma,
      we found no evidence of calcium entry through mechanically produced pores
      (mechanoporation). Rather, our results suggest that traumatic deformation of
      axons induces abnormal sodium influx through mechanically sensitive Na(+)
      channels, which subsequently triggers an increase in intra-axonal calcium via the
      opening of VGCCs and reversal of the Na(+)-Ca(2+) exchanger.

PMID- 11245678
TI  - Delayed neurodegeneration in neonatal rat thalamus after hypoxia-ischemia is
      apoptosis.
AB  - Brain injury in newborns can cause deficits in motor and sensory function. In
      most models of neonatal brain injury, thalamic damage often occurs. Using the
      Rice-Vannucci model of neonatal hypoxic-ischemic brain injury, we have shown that
      neuronal degeneration in somatosensory thalamus is delayed in onset (
      approximately 24 hr) compared with cortical and striatal injury and exhibits
      prominent structural features of apoptosis. In the present study, we examined
      whether cell death in the thalamus has molecular features of apoptosis. Fas death
      receptor protein expression increased rapidly after neonatal hypoxia-ischemia, in
      concert with cleavage of procaspase 8 to its active form. Concurrently, the
      levels of Bax in mitochondrial-enriched cell fractions increase, and cytochrome c
      accumulates in the soluble fraction. Mitochondria accumulate in a perinuclear
      distribution by 6 hr after hypoxia-ischemia. Cytochrome oxidase subunit 1 protein
      levels also increase at 6 hr after hypoxia-ischemia. Increased levels of Fas
      death receptor, Bax, and cytochrome c, activation of caspase 8, and abnormalities
      in mitochondria in the thalamus significantly precede the activation of caspase 3
      and the appearance of neuronal apoptosis at 24 hr. We conclude that the delayed
      neurodegeneration in neonatal rat ventral basal thalamus after hypoxic-ischemic
      injury is apoptosis mediated by death receptor activation.

PMID- 11245679
TI  - Domain interactions regulating ampa receptor desensitization.
AB  - Desensitization is a common property of glutamate and other ligand-gated ion
      channels, yet its molecular mechanism is unknown. For glutamate receptors,
      agonist binding involves interactions with identified amino acids from two lobes
      and may result in stabilizing the lobes in a closed "clamshell" conformation. The
      present studies demonstrate that two structures, beta-strands 7 and 8 and alpha
      helices J and K, functionally interact with each other and likely form hinges
      between the two lobes, influencing the coupling between agonist binding and
      desensitization. Two amino acids identified within these regions form a solvent
      exposed interface with a third amino acid, a mutation of which was shown
      previously to block receptor desensitization (L(507) in glutamate receptor 3).
      This interface may regulate a concerted conformational shift of the AMPA subtype
      of glutamate receptor subunits to the desensitized state.

PMID- 11245680
TI  - Evidence for redox regulation of cytochrome C release during programmed neuronal
      death: antioxidant effects of protein synthesis and caspase inhibition.
AB  - Sympathetic neurons die by apoptosis when they are deprived of nerve growth
      factor (NGF). Activation of caspases by cytochrome c released from mitochondria
      is central to this death. In this report we present evidence that cellular redox
      state regulates cytochrome c redistribution in these neurons. An increase of
      mitochondrial-produced reactive oxygen species (ROS) occurred in rat sympathetic
      neurons in cell culture within 3 hr of NGF withdrawal. Caspase inhibitors blocked
      this ROS burst. By 6 hr after NGF deprivation, glutathione (GSH) levels had
      increased, neutralizing elevated hydrogen peroxide levels and returning cellular
      redox state to basal levels. By 12 hr after deprivation, ROS levels had again
      increased and remained elevated during the rest of the apoptotic process. The
      later ROS burst appeared to have both caspase-dependent and caspase-independent
      components and was coincident with the period of cytochrome c release. Inhibition
      of protein synthesis with cycloheximide (CHX) and treatment with the antioxidant
      compound, N-acetyl-l-cysteine (l-NAC), blocked both the early and late ROS bursts
      by increasing cellular GSH levels (Ratan et al., 1994; Tan et al., 1998). Both
      compounds, and a membrane-permeant form of GSH, also inhibited cytochrome c
      release and death. Treatment of NGF, CHX-, l-NAC-, and GSH-saved cells with
      hydrogen peroxide caused rapid cytochrome c release. These data suggest a role
      for cellular redox state in regulating cytochrome c release during apoptosis
      induced by NGF withdrawal.

PMID- 11245681
TI  - Direct interaction of a brain voltage-gated K+ channel with syntaxin 1A:
      functional impact on channel gating.
AB  - Presynaptic voltage-gated K(+) (Kv) channels play a physiological role in the
      regulation of transmitter release by virtue of their ability to shape presynaptic
      action potentials. However, the possibility of a direct interaction of these
      channels with the exocytotic apparatus has never been examined. We report the
      existence of a physical interaction in brain synaptosomes between Kvalpha1.1 and
      Kvbeta subunits with syntaxin 1A, occurring, at least partially, within the
      context of a macromolecular complex containing syntaxin, synaptotagmin, and SNAP
      25. The interaction was altered after stimulation of neurotransmitter release.
      The interaction with syntaxin was further characterized in Xenopus oocytes by
      both overexpression and antisense knock-down of syntaxin. Direct physical
      interaction of syntaxin with the channel protein resulted in an increase in the
      extent of fast inactivation of the Kv1.1/Kvbeta1.1 channel. Syntaxin also
      affected the channel amplitude in a biphasic manner, depending on its
      concentration. At low syntaxin concentrations there was a significant increase in
      amplitudes, with no detectable change in cell-surface channel expression. At
      higher concentrations, however, the amplitudes decreased, probably because of a
      concomitant decrease in cell-surface channel expression, consistent with the role
      of syntaxin in regulation of vesicle trafficking. The observed physical and
      functional interactions between syntaxin 1A and a Kv channel may play a role in
      synaptic efficacy and neuronal excitability.

PMID- 11245682
TI  - Extracellular ATP or ADP induce chemotaxis of cultured microglia through Gi/o
      coupled P2Y receptors.
AB  - The initial microglial responses that occur after brain injury and in various
      neurological diseases are characterized by microglial accumulation in the
      affected sites of brain that results from the migration and proliferation of
      these cells. The early-phase signal responsible for this accumulation is likely
      to be transduced by rapidly diffusible factors. In this study, the possibility of
      ATP released from injured neurons and nerve terminals affecting cell motility was
      determined in rat primary cultured microglia. Extracellular ATP and ADP induced
      membrane ruffling and markedly enhanced chemokinesis in Boyden chamber assay.
      Further analyses using the Dunn chemotaxis chamber assay, which allows direct
      observation of cell movement, revealed that both ATP and ADP induced chemotaxis
      of microglia. The elimination of extracellular calcium or treatment with
      pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid, suramin, or adenosine-3'
      phosphate-5'-phosphosulfate did not inhibit ATP- or ADP-induced membrane
      ruffling, whereas AR-C69931MX or pertussis toxin treatments clearly did so. As an
      intracellular signaling molecule underlying these phenomena, the small G-protein
      Rac was activated by ATP and ADP stimulation, and its activation was also
      inhibited by pretreatment with pertussis toxin. These results strongly suggest
      that membrane ruffling and chemotaxis of microglia induced by ATP or ADP are
      mediated by G(i/o)-coupled P2Y receptors.

PMID- 11245683
TI  - Cell-specific expression of connexins and evidence of restricted gap junctional
      coupling between glial cells and between neurons.
AB  - The transmembrane connexin proteins of gap junctions link extracellularly to form
      channels for cell-to-cell exchange of ions and small molecules. Two primary
      hypotheses of gap junction coupling in the CNS are the following: (1) generalized
      coupling occurs between neurons and glia, with some connexins expressed in both
      neurons and glia, and (2) intercellular junctional coupling is restricted to
      specific coupling partners, with different connexins expressed in each cell type.
      There is consensus that gap junctions link neurons to neurons and astrocytes to
      oligodendrocytes, ependymocytes, and other astrocytes. However, unresolved are
      the existence and degree to which gap junctions occur between oligodendrocytes,
      between oligodendrocytes and neurons, and between astrocytes and neurons. Using
      light microscopic immunocytochemistry and freeze-fracture replica immunogold
      labeling of adult rat CNS, we investigated whether four of the best-characterized
      CNS connexins are each present in one or more cell types, whether
      oligodendrocytes also share gap junctions with other oligodendrocytes or with
      neurons, and whether astrocytes share gap junctions with neurons. Connexin32
      (Cx32) was found only in gap junctions of oligodendrocyte plasma membranes, Cx30
      and Cx43 were found only in astrocyte membranes, and Cx36 was only in neurons.
      Oligodendrocytes shared intercellular gap junctions only with astrocytes, with
      each oligodendrocyte isolated from other oligodendrocytes except via astrocyte
      intermediaries. Finally, neurons shared gap junctions only with other neurons and
      not with glial cells. Thus, the different cell types of the CNS express different
      connexins, which define separate pathways for neuronal versus glial gap
      junctional communication.

PMID- 11245684
TI  - Regulation of neurotransmitter vesicles by the homeodomain protein UNC-4 and its
      transcriptional corepressor UNC-37/groucho in Caenorhabditis elegans cholinergic
      motor neurons.
AB  - Motor neuron function depends on neurotransmitter release from synaptic vesicles
      (SVs). Here we show that the UNC-4 homeoprotein and its transcriptional
      corepressor protein UNC-37 regulate SV protein levels in specific Caenorhabditis
      elegans motor neurons. UNC-4 is expressed in four classes (DA, VA, VC, and SAB)
      of cholinergic motor neurons. Antibody staining reveals that five different
      vesicular proteins (UNC-17, choline acetyltransferase, Synaptotagmin,
      Synaptobrevin, and RAB-3) are substantially reduced in unc-4 and unc-37 mutants
      in these cells; nonvesicular neuronal proteins (Syntaxin, UNC-18, and UNC-11) are
      not affected, however. Ultrastructural analysis of VA motor neurons in the mutant
      unc-4(e120) confirms that SV number in the presynaptic zone is reduced (
      approximately 40%) whereas axonal diameter and synaptic morphology are not
      visibly altered. Because the UNC-4-UNC-37 complex has been shown to mediate
      transcriptional repression, we propose that these effects are performed via an
      intermediate gene. Our results are consistent with a model in which this unc-4
      target gene ("gene-x") functions at a post-transcriptional level as a negative
      regulator of SV biogenesis or stability. Experiments with a temperature-sensitive
      unc-4 mutant show that the adult level of SV proteins strictly depends on unc-4
      function during a critical period of motor neuron differentiation. unc-4 activity
      during this sensitive larval stage is also required for the creation of proper
      synaptic inputs to VA motor neurons. The temporal correlation of these events may
      mean that a common unc-4-dependent mechanism controls both the specificity of
      synaptic inputs as well as the strength of synaptic outputs for these motor
      neurons.

PMID- 11245685
TI  - Acetylcholine becomes the major excitatory neurotransmitter in the hypothalamus
      in vitro in the absence of glutamate excitation.
AB  - Glutamate and GABA are two major fast neurotransmitters (excitatory and
      inhibitory, respectively) in the CNS, including the hypothalamus. They play a key
      role in the control of excitation/inhibition balance and determine the activity
      and excitability of neurons in many neuronal circuits. Using neuronal cultures,
      whole-cell recording, Ca(2+) imaging, and Northern blots, we studied the
      compensatory regulation of neuronal activity during a prolonged decrease in
      glutamate excitation. We report here that after a chronic (6-17 d) blockade of
      ionotropic glutamate receptors, neurons in hypothalamic cultures revealed
      excitatory electrical and Ca(2+) synaptic activity, which was not elicited in the
      control cultures that were not subjected to glutamate blockade. This activity was
      suppressed with acetylcholine (ACh) receptor antagonists and was potentiated by
      eserine, an inhibitor of acetylcholinesterase, suggesting its cholinergic nature.
      The upregulation of ACh receptors and the contribution of ACh to the control of
      the excitation/inhibition balance in cultures after a prolonged decrease in
      glutamate activity were also demonstrated. Enhanced ACh transmission was also
      found in chronically blocked cerebellar but not cortical cultures, suggesting the
      region-specific character of glutamate-ACh interactions in the brain. We believe
      that in the absence of glutamate excitation in the hypothalamus in vitro, ACh, a
      neurotransmitter normally exhibiting only weak activity in the hypothalamus,
      becomes the major excitatory neurotransmitter and supports the
      excitation/inhibition balance. The increase in excitatory ACh transmission during
      a decrease in glutamate excitation may represent a novel form of neuronal
      plasticity that regulates activity and excitability of neurons during the
      glutamate/GABA imbalance.

PMID- 11245686
TI  - Regulation of microglial development: a novel role for thyroid hormone.
AB  - The postnatal development of rat microglia is marked by an important increase in
      the number of microglial cells and the growth of their ramified processes. We
      studied the role of thyroid hormone in microglial development. The distribution
      and morphology of microglial cells stained with isolectin B4 or monoclonal
      antibody ED1 were analyzed in cortical and subcortical forebrain regions of
      developing rats rendered hypothyroid by prenatal and postnatal treatment with
      methyl-thiouracil. Microglial processes were markedly less abundant in
      hypothyroid pups than in age-matched normal animals, from postnatal day 4 up to
      the end of the third postnatal week of life. A delay in process extension and a
      decrease in the density of microglial cell bodies, as shown by cell counts in the
      developing cingulate cortex of normal and hypothyroid animals, were responsible
      for these differences. Conversely, neonatal rat hyperthyroidism, induced by daily
      injections of 3,5,3'-triiodothyronine (T3), accelerated the extension of
      microglial processes and increased the density of cortical microglial cell bodies
      above physiological levels during the first postnatal week of life. Reverse
      transcription-PCR and immunological analyses indicated that cultured cortical
      ameboid microglial cells expressed the alpha1 and beta1 isoforms of nuclear
      thyroid hormone receptors. Consistent with the trophic and morphogenetic effects
      of thyroid hormone observed in situ, T3 favored the survival of cultured purified
      microglial cells and the growth of their processes. These results demonstrate
      that thyroid hormone promotes the growth and morphological differentiation of
      microglia during development.

PMID- 11245687
TI  - A unique role for Fyn in CNS myelination.
AB  - We analyzed the role of Fyn tyrosine kinase in CNS myelination by using fyn(-/-)
      null mutant mice, which express no Fyn protein. We found a severe myelin deficit
      in forebrain at all ages from 14 d to 1 year. The deficit was maximal at 1 month
      of age and was similar regardless of mouse strain background or whether it was
      determined by bulk isolation of myelin or by quantitation of myelin basic
      protein. To determine the cellular basis of the myelin deficit, we counted
      oligodendrocytes in tissue sections of mice expressing oligodendrocyte-targeted
      beta-galactosidase, and we used light and electron microscopy to examine the
      number and morphology of myelinated fibers and size of myelinated CNS structures.
      All of these parameters were reduced in fyn(-/-) mice. Unexpectedly, there were
      regional differences in the myelin deficit; in contrast to forebrain, fyn(-/-)
      cervical spinal cord exhibited no reduction in myelin content, number of
      oligodendrocytes, or number of myelinated fibers, nor was myelination delayed
      developmentally. We found that oligodendrocytes express Src, but there was no
      significant reduction of myelin content in null mutants lacking the Fyn-related
      kinases Src, Yes, or Lyn. Finally, we investigated the molecular features of Fyn
      that are required for myelination and found that a single amino acid
      substitution, which abolishes the tyrosine kinase activity of Fyn, resulted in a
      myelin deficit as great as that observed in the complete absence of Fyn protein.
      These results demonstrate that Fyn plays a unique role in myelination, one that
      requires its kinase activity.

PMID- 11245688
TI  - Reduced excitatory drive onto interneurons in the dentate gyrus after status
      epilepticus.
AB  - Impaired GABAergic inhibition may contribute to the development of
      hyperexcitability in epilepsy. We used the pilocarpine model of epilepsy to
      demonstrate that regulation of excitatory synaptic drive onto GABAergic
      interneurons is impaired during epileptogenesis. Synaptic input from granule
      cells (GCs), perforant path, and CA3 inputs onto hilar border interneurons of the
      dentate gyrus were examined in rat hippocampal slices during the latent period (1
      8 d) after induction of status epilepticus (SE). Short-term depression (STD) of
      GC inputs to interneurons induced by brief (500-800 msec), repetitive (5-20 Hz)
      stimulation, as well as paired-pulse depression at both GC and CA3 inputs to
      interneurons, were significantly (p < 0.05) enhanced in SE-experienced rats. In
      contrast, we found no significant differences between SE-experienced and age
      matched control rats in the properties of minimal EPSCs evoked at low frequency
      (0.3 Hz). Consistent with reduced GABAergic inhibition onto granule cells, paired
      pulse depression of perforant path-evoked granule cell population spikes was lost
      in SE-experienced rats. Enhanced STD was partially mediated by group II
      metabotropic glutamate receptors, because the selective antagonist, 2S-2-amino-2
      (1S,2S-2-carboxycyclopropyl-1-yl)-3-(xanth-9-yl)propanoic acid, attenuated STD in
      SE-experienced rats but had no effect on STD of GC inputs in the normal adult
      rat. The group II mGluR agonist, (2S',1R',2R',3R')-2-(2,3-dicarboxylcyclopropyl)
      glycine (1 micrometer), produced a greater depression of GC input to hilar border
      interneurons in SE-experienced rats than in controls. These results indicate
      that, in the SE-experienced rat, excitatory drive to hilar border inhibitory
      interneurons is weakened through a use-dependent mechanism involving group II
      metabotropic glutamate receptors.

PMID- 11245689
TI  - Reduction of potassium currents and phosphatidylinositol 3-kinase-dependent AKT
      phosphorylation by tumor necrosis factor-(alpha) rescues axotomized retinal
      ganglion cells from retrograde cell death in vivo.
AB  - Tumor-necrosis-factor-alpha (TNF-alpha) prevented secondary death of retinal
      ganglion cells (RGCs) after axotomy of the optic nerve in vivo. This RGC rescue
      was confirmed in vitro in a mixed retinal culture model. In accordance with our
      previous findings, TNF-alpha decreased outward potassium currents in RGCs.
      Antagonism of the TNF-alpha-induced decrease in outward potassium currents with
      the potassium channel opener minoxidilsulfate (as verified by electrophysiology)
      abolished neuroprotection. Western blot analysis revealed an upregulation of
      phospho-Akt as a consequence of TNF-alpha-induced potassium current reduction.
      Inhibition of the phosphatidylinositol 3-kinase-Akt pathway with wortmannin
      decreased TNF-alpha-promoted RGC survival. These data point to a functionally
      relevant cytokine-dependent neuroprotective signaling cascade in adult CNS
      neurons.

PMID- 11245690
TI  - The primate amygdala mediates acute fear but not the behavioral and physiological
      components of anxious temperament.
AB  - Temperamentally anxious individuals can be identified in childhood and are at
      risk to develop anxiety and depressive disorders. In addition, these individuals
      tend to have extreme asymmetric right prefrontal brain activity. Although common
      and clinically important, little is known about the pathophysiology of anxious
      temperament. Regardless, indirect evidence from rodent studies and difficult to
      interpret primate studies is used to support the hypothesis that the amygdala
      plays a central role. In previous studies using rhesus monkeys, we characterized
      an anxious temperament endophenotype that is associated with excessive anxiety
      and fear-related responses and increased electrical activity in right frontal
      brain regions. To examine the role of the amygdala in mediating this
      endophenotype and other fearful responses, we prepared monkeys with selective
      fiber sparing ibotenic acid lesions of the amygdala. Unconditioned trait-like
      anxiety-fear responses remained intact in monkeys with >95% bilateral amygdala
      destruction. In addition, the lesions did not affect EEG frontal asymmetry.
      However, acute unconditioned fear responses, such as those elicited by exposure
      to a snake and to an unfamiliar threatening conspecific were blunted in monkeys
      with >70% lesions. These findings demonstrate that the primate amygdala is
      involved in mediating some acute unconditioned fear responses but challenge the
      notion that the amygdala is the key structure underlying the dispositional
      behavioral and physiological characteristics of anxious temperament.

PMID- 11245691
TI  - Linked target selection for saccadic and smooth pursuit eye movements.
AB  - In natural situations, motor activity must often choose a single target when
      multiple distractors are present. The present paper asks how primate smooth
      pursuit eye movements choose targets, by analysis of a natural target-selection
      task. Monkeys tracked two targets that started 1.5 degrees eccentric and moved in
      different directions (up, right, down, and left) toward the position of fixation.
      As expected from previous results, the smooth pursuit before the first saccade
      reflected a vector average of the responses to the two target motions
      individually. However, post-saccadic smooth eye velocity showed enhancement that
      was spatially selective for the motion at the endpoint of the saccade. If the
      saccade endpoint was close to one of the two targets, creating a targeting
      saccade, then pursuit was selectively enhanced for the visual motion of that
      target and suppressed for the other target. If the endpoint landed between the
      two targets, creating an averaging saccade, then post-saccadic smooth eye
      velocity also reflected a vector average of the two target motions. Saccades with
      latencies >200 msec were almost always targeting saccades. However, pursuit did
      not transition from vector-averaging to target-selecting until the occurrence of
      a saccade, even when saccade latencies were >300 msec. Thus, our data demonstrate
      that post-saccadic enhancement of pursuit is spatially selective and that noncued
      target selection for pursuit is time-locked to the occurrence of a saccade. This
      raises the possibility that the motor commands for saccades play a causal role,
      not only in enhancing visuomotor transmission for pursuit but also in choosing a
      target for pursuit.

PMID- 11245692
TI  - Estrogen biphasically modifies hypothalamic GABAergic function concomitantly with
      negative and positive control of luteinizing hormone release.
AB  - The principal role of estrogen is its control of the female ovulatory cycle via
      negative and positive feedback on gonadotropin secretion. However, a detailed,
      cohesive picture of how the steroid specifically regulates the excitability of
      hypothalamic neurons involved in the central control of gonadotropin secretion is
      still emerging. Here, we used an ovariectomized female guinea pig model to test
      the hypothesis that estrogen acts on GABAergic neurons in the preoptic area (POA)
      to elicit a biphasic profile of luteinizing hormone (LH) secretion. Intracellular
      electrophysiological recordings revealed that estradiol benzoate (EB; 25
      microgram, s.c.) decreased the hyperpolarizing response of GABAergic neurons to
      the GABA(B) receptor agonist baclofen 24 hr after treatment. This effect of
      GABA(B) receptor stimulation in unidentified POA neurons was still depressed 42
      hr after EB administration. By the use of a ribonuclease protection assay,
      however, EB reduced glutamic acid decarboxylase mRNA expression 42 hr but not 24
      hr after its administration. Thus, estrogen attenuated the autoinhibition of
      GABAergic POA neurons during the initial LH suppressive (i.e., negative feedback)
      phase and subsequently reduced GABAergic function during the LH surge (i.e.,
      positive feedback). These studies demonstrate that the effects of estrogen on
      hypothalamic GABAergic neurons coincide with the inhibitory and stimulatory
      actions, respectively, of the steroid on LH secretion. Furthermore, the data
      provide novel insights into the mechanism by which estrogen regulates
      hypothalamic GABAergic neurons, which are critical for the biphasic modulation of
      LH release observed over the course of the female ovulatory cycle.

PMID- 11245693
TI  - Reduced neurogenesis after neonatal seizures.
AB  - Although neonatal seizures are quite common, there is controversy regarding their
      consequences. Despite considerable evidence that seizures may cause less cell
      loss in young animals compared with mature animals, there are nonetheless clear
      indications that seizures may have other potentially deleterious effects. Because
      it is known that seizures in the mature brain can increase neurogenesis in the
      hippocampus, we studied the extent of neurogenesis in the granule cell layer of
      the dentate gyrus over multiple time points after a series of 25 flurothyl
      induced seizures administered between postnatal day 0 (P0) and P4. Rats with
      neonatal seizures had a significant reduction in the number of the thymidine
      analog 5-bromo-2'-deoxyuridine-5'-monophosphate- (BrdU) labeled cells in the
      dentate gyrus and hilus compared with the control groups when the animals were
      killed either 36 hr or 2 weeks after the BrdU injections. The reduction in BrdU
      labeled cells continued for 6 d after the last seizure. BrdU-labeled cells
      primarily colocalized with the neuronal marker neuron-specific nuclear protein
      and rarely colocalized with the glial cell marker glial fibrillary acidic
      protein, providing evidence that a very large percentage of the newly formed
      cells were neurons. Immature rats subjected to a single seizure did not differ
      from controls in number of BrdU-labeled cells. In comparison, adult rats
      undergoing a series of 25 flurothyl-induced seizures had a significant increase
      in neurogenesis compared with controls. This study indicates that, after
      recurrent seizures in the neonatal rat, there is a reduction in newly born
      granule cells.

PMID- 11245694
TI  - Membrane potential and conductance changes underlying length tuning of cells in
      cat primary visual cortex.
AB  - Spike responses for many cells of cat primary visual cortex are optimized for the
      length of a drifting grating stimulus. Stimuli that are longer or shorter than
      this optimal length elicit submaximal spike responses. To investigate the
      mechanisms responsible for this length tuning, we have recorded intracellularly
      from visual cortical neurons in the cat while presenting drifting grating stimuli
      of varying lengths. We have found that the membrane potential responses of the
      cells also exhibit length tuning, but that the suppression of spike responses at
      lengths longer than the preferred is 30-50% stronger than the corresponding
      suppression of the membrane potential responses. This difference may be
      attributed to the effects of spike threshold. Furthermore, using steady injected
      currents, we have measured changes in the excitatory and inhibitory components of
      input conductance evoked by stimuli of different lengths. We find that, compared
      with optimal stimuli, long stimuli evoke both an increase in inhibitory
      conductance and a decrease in excitatory conductance. These two mechanisms differ
      in their contrast sensitivity, resulting in stronger end stopping and shorter
      optimal lengths for high-contrast stimuli. These patterns suggest that response
      suppression for long stimuli is generated by a combination of active inhibition
      from stimuli outside the excitatory receptive field, as well as decreased
      excitation from other cortical cells that are themselves end-inhibited.

PMID- 11245695
TI  - Symmetry, stereotypy, and topography of odorant representations in mouse
      olfactory bulbs.
AB  - The molecular basis of vertebrate odorant representations has been derived
      extensively from mice. The functional correlates of these molecular features were
      visualized using optical imaging of intrinsic signals in mouse olfactory bulbs.
      Single odorants activated clusters of glomeruli in consistent, restricted
      portions of the bulb. Patterns of activated glomeruli were clearly bilaterally
      symmetric and consistent in different individual mice, but the precise number,
      position, and intensity of activated glomeruli in the two bulbs of the same
      individual and between individuals varied considerably. Representations of
      aliphatic aldehydes of different carbon chain length shifted systematically along
      a rostral-caudal strip of the dorsal bulb, indicating a functional topography of
      odorant representations. Binary mixtures of individual aldehydes elicited
      patterns of glomerular activation that were topographic combinations of the maps
      for each individual odor. Thus the principles derived from the molecular
      organization of a small subset of murine olfactory receptor neuron projection
      patterns-bilateral symmetry, local clustering, and local variability-are reliable
      guides to the initial functional representation of odorant molecules.

PMID- 11245696
TI  - Sexual behavior induction of c-Fos in the nucleus accumbens and amphetamine
      stimulated locomotor activity are sensitized by previous sexual experience in
      female Syrian hamsters.
AB  - Dopamine transmission in the nucleus accumbens can be activated by drugs, stress,
      or motivated behaviors, and repeated exposure to these stimuli can sensitize this
      dopamine response. The objectives of this study were to determine whether female
      sexual behavior activates nucleus accumbens neurons and whether past sexual
      experience cross-sensitizes neuronal responses in the nucleus accumbens to
      amphetamine. Using immunocytochemical labeling, c-Fos expression in different
      subregions (shell vs core at the rostral, middle, and caudal levels) of the
      nucleus accumbens was examined in female hamsters that had varying amounts of
      sexual experience. Female hamsters, given either 6 weeks of sexual experience or
      remaining sexually naive, were tested for sexual behavior by exposure to adult
      male hamsters. Previous sexual experience increased c-Fos labeling in the rostral
      and caudal levels but not in the middle levels of the nucleus accumbens. Testing
      for sexual behavior increased labeling in the core, but not the shell, of the
      nucleus accumbens. To validate that female sexual behavior can sensitize neurons
      in the mesolimbic dopamine pathway, the locomotor responses of sexually
      experienced and sexually naive females to an amphetamine injection were then
      compared. Amphetamine increased general locomotor activity in all females.
      However, sexually experienced animals responded sooner to amphetamine than did
      sexually naive animals. These data indicate that female sexual behavior can
      activate neurons in the nucleus accumbens and that sexual experience can cross
      sensitize neuronal responses to amphetamine. In addition, these results provide
      additional evidence for functional differences between the shell and core of the
      nucleus accumbens and across its anteroposterior axis.

PMID- 11245697
TI  - Selective processing of vestibular reafference during self-generated head motion.
AB  - The vestibular sensory apparatus and associated vestibular nuclei are generally
      thought to encode head-in-space motion. Angular head-in-space velocity is
      detected by vestibular hair cells that are located within the semicircular canals
      of the inner ear. In turn, the afferent fibers of the vestibular nerve project to
      neurons in the vestibular nuclei, which, in head-restrained animals, similarly
      encode head-in-space velocity during passive whole-body rotation. However, during
      the active head-on-body movements made to generate orienting gaze shifts, neurons
      in the vestibular nuclei do not reliably encode head-in-space motion. The
      mechanism that underlies this differential processing of vestibular information
      is not known. To address this issue, we studied vestibular nuclei neural
      responses during passive head rotations and during a variety of tasks in which
      alert rhesus monkeys voluntarily moved their heads relative to space. Neurons
      similarly encoded head-in-space velocity during passive rotations of the head
      relative to the body and during passive rotations of the head and body together
      in space. During all movements that were generated by activation of the neck
      musculature (voluntary head-on-body movements), neurons were poorly modulated. In
      contrast, during a task in which each monkey actively "drove" its head and body
      together in space by rotating a steering wheel with its arm, neurons reliably
      encoded head-in-space motion. Our results suggest that, during active head-on
      body motion, an efferent copy of the neck motor command, rather than the monkey's
      knowledge of its self-generated head-in-space motion or neck proprioceptive
      information, gates the differential processing of vestibular information at the
      level of the vestibular nuclei.

PMID- 11245698
TI  - NMDA and AMPA antagonist infusions into the ventral striatum impair different
      steps of spatial information processing in a nonassociative task in mice.
AB  - Most of the research on ventral striatal functions has been focused on their role
      in modulating reward and motivation. More recently, a possible role of this
      structure in cognitive functions has been suggested. However, very little
      information is available on the involvement of the nucleus accumbens in the
      different stages of the consolidation process. In this study, the effect of focal
      injections of AP-5 and DNQX, competitive antagonists at the NMDA and AMPA
      receptors, respectively, was examined in a nonassociative task designed to
      estimate the ability of mice to react to spatial changes. The task consists of
      placing the animals in an open field containing five objects; after three
      sessions of habituation, their reactivity to object displacement was examined 24
      hr later. AP-5 injections administered after training impaired the ability of
      mice to detect the spatial novelty but did not affect response when injected 120
      min after training or before testing. On the contrary, DNQX did not affect
      response when administered immediately or 120 min after training but did impair
      spatial discrimination when administered before training or testing. These data
      demonstrate a double dissociation between glutamate receptor subtypes, such that
      accumbens NMDA receptors are important for consolidation and not ongoing
      discrimination of spatial information, whereas AMPA receptors have an opposite
      role in these processes.

PMID- 11245699
TI  - Tension distribution to the five digits of the hand by neuromuscular compartments
      in the macaque flexor digitorum profundus.
AB  - The macaque flexor digitorum profundus (FDP) consists of a muscle belly with four
      neuromuscular regions and a complex insertion tendon that divides to serve all
      five digits of the hand. To determine the extent to which compartments within FDP
      act on single versus multiple digits, we stimulated the primary nerve branch
      innervating each neuromuscular region while recording the tension in all five
      distal insertion tendons. Stimulation of each primary nerve branch activated a
      distinct region of the muscle belly, so that each primary nerve branch and the
      muscle region innervated can be considered a neuromuscular compartment. Although
      each neuromuscular compartment provided a distinct distribution of tension across
      the five distal tendons, none acted on only one digital tendon. Most of the
      distribution of tension to multiple digits could be attributed to passive
      biomechanical interactions in the complex insertion tendon, although for the
      larger compartments a wider distribution resulted from the broad insertion of the
      muscle belly. Nerve ligations excluded contributions of spinal reflexes or distal
      axon reflexes to the distribution of tension to multiple digits. We conclude that
      the macaque FDP consists of four neuromuscular compartments, each of which
      provides a distinct distribution of tension to multiple digits.

PMID- 11245700
TI  - Parabrachial internal lateral neurons convey nociceptive messages from the deep
      laminas of the dorsal horn to the intralaminar thalamus.
AB  - This study investigates the physiological properties of parabrachial internal
      lateral (PBil) neurons that project to the paracentral thalamic (PC) nucleus
      using antidromic activation and single-unit recording techniques in anesthetized
      rat. We reported here that most of these neurons responded exclusively to the
      nociceptive stimulation of large receptive fields with a sustained firing that
      often outlasted the stimulus up to several minutes. These responses were
      depressed by intravenous morphine. Our results demonstrated a novel spino-PBil-PC
      pathway, which transmits nociceptive messages to the PC nucleus, which in turn
      projects to the prefrontal cortex. Recent clinical imaging studies showed the
      important participation of prefrontal cortex in emotional response to pain. This
      spino-PBil-PC pathway may explain how nociceptive messages reach the prefrontal
      cortex and thus trigger unbearable aversive aspects of pain.

PMID- 11245701
TI  - GABA(A) receptors containing (alpha)5 subunits in the CA1 and CA3 hippocampal
      fields regulate ethanol-motivated behaviors: an extended ethanol reward
      circuitry.
AB  - GABA receptors within the mesolimbic circuitry have been proposed to play a role
      in regulating alcohol-seeking behaviors in the alcohol-preferring (P) rat.
      However, the precise GABA(A) receptor subunit(s) mediating the reinforcing
      properties of EtOH remains unknown. We examined the capacity of intrahippocampal
      infusions of an alpha5 subunit-selective ( approximately 75-fold) benzodiazepine
      (BDZ) inverse agonist [i.e., RY 023 (RY) (tert-butyl 8-(trimethylsilyl) acetylene
      5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5a] [1,4] benzodiazepine-3-carboxylate)]
      to alter lever pressing maintained by concurrent presentation of EtOH (10% v/v)
      and a saccharin solution (0.05% w/v). Bilateral (1.5-20 microgram) and unilateral
      (0.01-40 microgram) RY dose-dependently reduced EtOH-maintained responding, with
      saccharin-maintained responding being reduced only with the highest doses (e.g.,
      20 and 40 microgram). The competitive BDZ antagonist ZK 93426 (ZK) (7 microgram)
      reversed the RY-induced suppression on EtOH-maintained responding, confirming
      that the effect was mediated via the BDZ site on the GABA(A) receptor complex.
      Intrahippocampal modulation of the EtOH-maintained responding was site-specific;
      no antagonism by RY after intra-accumbens [nucleus accumbens (NACC)] and
      intraventral tegmental [ventral tegmental area (VTA)] infusions was observed.
      Because the VTA and NACC contain very high densities of alpha1 and alpha2
      subunits, respectively, we determined whether RY exhibited a "negative" or
      "neutral" pharmacological profile at recombinant alpha1beta3gamma2,
      alpha2beta3gamma2, and alpha5beta3gamma2 receptors expressed in Xenopus oocytes.
      RY produced "classic" inverse agonism at all alpha receptor subtypes; thus, a
      neutral efficacy was not sufficient to explain the failure of RY to alter EtOH
      responding in the NACC or VTA. The results provide the first demonstration that
      the alpha5-containing GABA(A) receptors in the hippocampus play an important role
      in regulating EtOH-seeking behaviors.

PMID- 11245702
TI  - Functional consequences of 5-HT transporter gene disruption on 5-HT(1a) receptor
      mediated regulation of dorsal raphe and hippocampal cell activity.
AB  - The consequences of the absence of 5-HT reuptake on the functional properties of
      5-HT(1A) receptors were examined in the dorsal raphe nucleus and the hippocampus
      of knock-out mice lacking the serotonin transporter (5-HTT). Extracellular
      recordings showed that application of selective 5-HT reuptake inhibitors such as
      paroxetine and citalopram onto brainstem slices resulted in a concentration
      dependent inhibition of 5-HT neuron firing in the dorsal raphe nucleus of wild
      type 5-HTT+/+ mice, but not 5-HTT-/- mutants. By contrast, the 5-HT(1A) receptor
      agonists ipsapirone and 5-carboxamidotryptamine inhibited the discharge in both
      groups. However, the potency of these agonists was markedly decreased (by
      approximately 55- and approximately 6-fold, respectively) in 5-HTT-/- compared
      with 5-HTT+/+ animals. Similarly, intracellular recordings showed that the
      potency of 5-carboxamidotryptamine to hyperpolarize 5-HT neurons in the dorsal
      raphe nucleus was significantly lower in 5-HTT-/- than in 5-HTT+/+ animals. These
      data contrasted with those obtained with hippocampal slices in which 5
      carboxamidotryptamine was equipotent to hyperpolarize CA1 pyramidal neurons in
      both mutant and wild-type mice. As expected from their mediation through 5-HT(1A)
      receptors, the effects of ipsapirone and 5-carboxamidotryptamine were
      competitively inhibited by the selective 5-HT(1A) antagonist WAY 100635 in both
      groups. These data showed that 5-HTT gene knock-out induced a marked
      desensitization of 5-HT(1A) autoreceptors in the dorsal raphe nucleus without
      altering postsynaptic 5-HT(1A) receptor functioning in the hippocampus.
      Similarities between these changes and those evoked by chronic treatment with 5
      HT reuptake inhibitors emphasize the existence of regional differences in 5
      HT(1A) receptor regulatory mechanisms.

PMID- 11245703
TI  - Cellular imaging of zif268 expression in the hippocampus and amygdala during
      contextual and cued fear memory retrieval: selective activation of hippocampal
      CA1 neurons during the recall of contextual memories.
AB  - The neuroanatomical and molecular basis of fear memory retrieval was studied by
      analyzing the expression of the plasticity-associated immediate early gene
      zif268. Cellular quantitative in situ hybridization revealed that zif268 is
      expressed within specific regions of the hippocampus and amygdala during fear
      memory retrieval. Within the hippocampus, increased expression of zif268 was
      observed within CA1 neurons, but not dentate gyrus neurons, during the retrieval
      of contextual, but not cued, fear associations. In contrast, zif268 expression
      was increased within neurons of the amygdala (lateral, basal, and central nuclei)
      during the retrieval of both contextual and cued fear memories. These results
      demonstrate activation of hippocampal CA1 neurons in contextual fear memory
      retrieval that was not merely a correlate of the behavioral expression of fear
      itself, because it was limited to the retrieval of contextual, and not cued, fear
      memories. Further studies revealed that the selective increase in hippocampal CA1
      zif268 expression seen after contextual fear memory retrieval was limited to the
      retrieval of recent (24 hr) but not older (28 d) memories. These experiments
      represent the first demonstration that zif268 expression in specific neuronal
      populations is associated with memory retrieval and suggest that this gene may
      contribute to plasticity and reconsolidation accompanying the retrieval process.

PMID- 11245704
TI  - The amygdala is essential for the development of neuronal plasticity in the
      medial geniculate nucleus during auditory fear conditioning in rats.
AB  - The medial geniculate nucleus of the thalamus (MGN) and the basolateral complex
      of the amygdala (BLA) are critical components of the neural circuit that mediates
      auditory fear conditioning. Several studies indicate that neurons in both the MGN
      and BLA exhibit associative plasticity of spike firing during auditory fear
      conditioning. In the present study, we examined whether the development of
      plasticity in the MGN requires the BLA. Single units were recorded from chronic
      multichannel electrodes implanted in the medial division of the MGN of conscious
      and freely moving rats. Rats received auditory fear conditioning trials, which
      consisted of a white-noise conditional stimulus (CS) and a co-terminating
      footshock unconditional stimulus (US). Unpaired (sensitization) controls received
      the same number of trials as paired animals, but the CS and US were explicitly
      unpaired. Before fear conditioning, rats received either an intra-amygdala
      infusion of muscimol, a GABA(A) receptor agonist, to inactivate BLA neurons or an
      infusion of the saline vehicle. Auditory fear conditioning produced a substantial
      increase in both CS-elicited spike firing in the MGN and conditional freezing
      behavior in vehicle-treated rats receiving paired training. Muscimol inactivation
      of the BLA severely attenuated the development of both conditioning-related
      increases in CS-elicited spike firing in the MGN and conditional freezing to the
      auditory CS. Unpaired training did not yield increases in either CS-elicited
      spike firing or freezing to the tone CS. These results reveal that the BLA is
      essential to the development of plasticity in the auditory thalamus during fear
      conditioning.

PMID- 11245705
TI  - Evidence for a common binding cavity for three general anesthetics within the
      GABAA receptor.
AB  - The GABA(A) receptor is an important target for a variety of general anesthetics
      (Franks and Lieb, 1994) and for benzodiazepines such as diazepam. Specific point
      mutations in the GABA(A) receptor selectively abolish regulation by
      benzodiazepines (Rudolph et al., 1999; McKernan et al., 2000) and by anesthetic
      ethers (Mihic et al., 1997; Krasowski et al., 1998; Koltchine et al., 1999),
      suggesting the existence of discrete binding sites on the GABA(A) receptor for
      these drugs. Using anesthetics of different molecular size (isoflurane >
      halothane > chloroform) together with complementary mutagenesis of specific amino
      acid side chains, we estimate the volume of a proposed anesthetic binding site as
      between 250 and 370 A(3). The results of the "cutoff" analysis suggest a common
      site of action for the anesthetics isoflurane, halothane, and chloroform on the
      GABA(A) receptor. Moreover, the data support a crucial role for Leu232, Ser270,
      and Ala291 in the alpha subunit in defining the boundaries of an amphipathic
      cavity, which can accommodate a variety of small general anesthetic molecules.

PMID- 11245706
TI  - New treatments for tics?

PMID- 11245707
TI  - Rett syndrome: "We'll keep the genes on for you".

PMID- 11245708
TI  - A profile of neurology practice based on Medicare services: an AAN Medical
      Economics and Management Committee report. American Academy of Neurology.
AB  - OBJECTIVE: This report uses Medicare data to provide insight into the patient
      care services most often provided by neurologists. METHODS: The 1998 Medicare
      data set for physician services was obtained from the Health Care Financing
      Administration. Neurologists' services were tabulated and compared to the 1998
      American Academy of Neurology Member Demographic and Practice Characteristics
      Report. A profile was derived of neurologists' typical services. RESULTS: Patient
      visits represent 70% of neurologists' services when evaluated by income. Office
      was the site of service for 62% of patient visit income. Established patients
      were 29% of patient visit income. Neurologists frequently code patient visits at
      levels of service higher than used by other physicians. EMG and nerve conduction
      velocity together represent 55% of neurodiagnostic services when evaluated by
      income. CONCLUSIONS: Patient care continues to be the main service of
      neurologists, with office care more than hospital care. Established patient care
      is an important part of patient services, confirming the role of the neurologist
      in principal care. Neurologists' patient care levels of service are higher than
      for other physicians.

PMID- 11245709
TI  - Baclofen treatment in Tourette syndrome: a double-blind, placebo-controlled,
      crossover trial.
AB  - OBJECTIVE: To investigate the effectiveness of baclofen for the treatment of tics
      in children with Tourette syndrome (TS). BACKGROUND: Baclofen, which contains
      both gamma-aminobutyric acid (GABA) and phenylethylamine moieties, was suggested
      in an open-label protocol to be an effective treatment for TS. This is a double
      blind, placebo-controlled study to investigate this medication in children with
      TS. METHODS: Subjects received, in a randomized sequence, 4-week medication
      cycles of baclofen (20 mg three times daily) and placebo with a 2-week
      intervening washout period between the cycles. Outcome measures included the
      Clinical Global Impression (CGI) scale, and the Yale Global Tic Severity Scale
      (YGTSS), the latter including subscales for total tics and overall impairment.
      Measures were assessed at baseline and on days 28, 42, and 70 of the study.
      RESULTS: Ten children (seven boys and three girls, aged 8 to 14) with TS
      participated. Nine subjects completed the protocol; one dropped out for
      psychosocial reasons. No major side effects were reported. The mean change in CGI
      score (-0.9) after 4 weeks of baclofen treatment as compared with placebo
      treatment showed a significant improvement (95% CI, -1.7 to -0.1; p = 0.04). All
      subjects showed some amelioration in total YGTSS score during baclofen treatment.
      The mean change in total YGTSS score (-14.7) approached significance (95% CI, 
      30.3 to 0.9; p = 0.06). Examination of differences between baclofen and placebo
      treatment groups expressed as a percent change from baseline showed that baclofen
      had a statistically significant effect on both outcome measures. Subscales of the
      YGTSS showed that the reduction in total tic scores was primarily due to a
      reduction in the impairment score rather than a decrease in tics. CONCLUSIONS:
      Children with TS may benefit from treatment with baclofen, although improvements
      may be related to factors other than tics. Larger studies directly comparing
      baclofen against other tic-suppressing agents are recommended.

PMID- 11245710
TI  - Botulinum toxin for simple motor tics: a randomized, double-blind, controlled
      clinical trial.
AB  - OBJECTIVE: To determine the effect of injections of botulinum toxin on simple
      motor tics. BACKGROUND: Case series with unblinded assessments have reported
      improvement in tic frequency and associated urge with botulinum toxin. METHODS:
      Patients with suitable simple motor tics were randomized to receive botulinum
      toxin and placebo in a double blind, crossover design. All outcomes compared week
      2 to baseline measurements. The primary outcome measure was the number of treated
      tics per minute on a videotape segment. Secondary outcome measures were number of
      untreated tics per minute, the Shapiro Tourette Syndrome Severity Scale score, a
      numerical assessment of the urge to perform the treated tic (0 to 4), the
      premonitory sensation associated with the treated tic (0 to 4), and the patient's
      global impression of change. RESULTS: Eighteen patients completed the study. The
      median relative change in treated tics per minute with botulinum toxin was -0.39
      (or a 39% reduction) versus 0.058 (or a 5.8% increase) with placebo (net effect 
      0.37, p = 0.0007). The average change in urge scores (score range 0 to 4) was 
      0.46 in the treatment phase and +0.49 in the placebo phase (net effect 0.94, p =
      0.02). Other secondary outcome measures were not significantly different between
      the two groups. CONCLUSION: Botulinum toxin reduced treated tic frequency and the
      urge associated with the treated tic. Despite these changes, patients did not
      report an overall benefit from the treatment. Careful consideration of the
      contribution of the target tic to the patient's disability is needed before
      making treatment decisions.

PMID- 11245711
TI  - Leukoaraiosis three-dimensional in Binswanger disease.

PMID- 11245712
TI  - MECP2 gene analysis in classical Rett syndrome and in patients with Rett-like
      features.
AB  - OBJECTIVE: To discuss the diagnostic criteria for Rett syndrome based on
      mutational screening of the methyl-CpG-binding protein 2 gene ( MECP2 ) in
      patients with classic Rett syndrome and patients with Rett-like features.
      METHODS: Thirty-nine patients with classical Rett syndrome, one with preserved
      speech variant (PSV), and 12 patients with developmental delay and some features
      of Rett syndrome were recruited for sequence analysis of the MECP2 gene coding
      region. The phenotype of the patients was correlated with the presence and type
      of the mutation as well as the X-chromosome inactivation (XCI) pattern. RESULTS:
      found in 100% of the patients with classical Rett syndrome originating from
      Finland. One novel mutation, P127L, was detected in a patient with PSV. No
      mutations were found in other cases. The XCI status was found to be random in 72%
      of the patients with classical Rett syndrome, including the patient with PSV and
      all patients with developmental delay informative for the analysis. CONCLUSIONS:
      An MECP2 mutation can be found in almost every patient with classical Rett
      syndrome. More patients need to be analyzed in order to clarify the mutation
      prevalence in patients with atypical Rett syndrome and in patients with mental
      retardation.

PMID- 11245713
TI  - Cognitive status and quality of life in patients with suspected versus proven low
      grade gliomas.
AB  - BACKGROUND: The preferred management of patients with suspected low-grade gliomas
      (S-LGG) remains controversial. The benefits of resection or radiotherapy early in
      the course of the disease have not been proven in terms of survival. Little is
      known about the effects of early therapy on quality of life (QOL) and cognitive
      status. The authors compared functional status, QOL, and cognitive status of
      patients suspected of having a LGG, in whom treatment was deferred, and patients
      with proven LGG (P-LGG), who underwent early surgery. METHODS: The authors
      recruited 24 patients suspected of having an LGG. These patients were matched
      with 24 patients with a histologically proven LGG and healthy control subjects
      for educational level, handedness, age, and gender. The two patient groups were
      also matched for tumor laterality, use of anticonvulsants, and interval between
      diagnosis and testing. Functional status was determined in both patient groups.
      QOL and cognitive status were compared between the three groups. RESULTS:
      Matching criteria and functional status did not differ significantly between
      groups. Both patient groups scored worse on QOL scales than healthy control
      subjects. Unoperated patients with S-LGG scored better on most items than
      patients with P-LGG. Cognitive status was worse in both groups than in healthy
      control subjects, but, again, patients with S-LGG performed better than patients
      with P-LGG. CONCLUSION: These data suggest that a wait-and-see policy in patients
      with S-LGG has no negative effect on cognitive performance and QOL.

PMID- 11245714
TI  - Use of specialized coagulation testing in the evaluation of patients with acute
      ischemic stroke.
AB  - OBJECTIVE: To investigate the use and appropriateness of specialized coagulation
      tests in the evaluation of patients with acute ischemic stroke and identify
      factors that influence test ordering. BACKGROUND: Coagulation abnormalities are a
      rare but recognized cause of ischemic stroke. METHODS: Patient demographics,
      stroke risk factors, history of venous thrombosis or miscarriage, family history
      of stroke, and the results of specialized tests for coagulation disorders were
      recorded for a consecutive series of ischemic stroke patients over age 18
      admitted to an academic medical center over 3 years (n = 674). Factors associated
      with testing were identified with univariate analyses in a random sample of two
      thirds of the patients (n = 450). Multivariate logistic regression modeling was
      then used to identify variables independently associated with testing and then
      validated in the remaining patients (n = 224). RESULTS: Of the 31% of patients (n
      = 208) tested for coagulopathies, 29% (n = 60) were tested when the result was
      unlikely to influence therapeutic decisions. Historical factors associated with
      an increased incidence of a coagulopathy, such as history of venous thrombosis or
      miscarriage, were not commonly documented. The absence of small-artery
      atherosclerosis (OR 0.36, 95% CI 0.17 to 0.76) and younger age (OR 0.89 per year,
      95% CI 0.87 to 0.92) were independently related to the frequency of specialized
      coagulation testing. CONCLUSIONS: One-third of specialized coagulation tests were
      ordered when the test results were unlikely to affect therapeutic decisions. Age
      was the only clinical factor increasing the likelihood of a coagulopathy that
      appeared to influence ordering of specialized coagulation tests.

PMID- 11245715
TI  - MRI hyperintensities of the temporal lobe and external capsule in patients with
      CADASIL.
AB  - BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts
      and leukoencephalopathy (CADASIL) is an inherited, autosomal dominant condition
      caused by mutations of the Notch3 gene. Affected individuals have migraine, mood
      disturbance, and recurrent strokes, often progressing to subcortical dementia and
      premature death. MRI findings include focal lacunar infarcts and diffuse T2
      weighted hyperintensity, or leukoaraiosis. However, such findings are seen much
      more commonly in patients with cardiovascular risk factors, particularly
      hypertension, where they are believed to represent cerebral small vessel disease.
      No previous study has sought to identify specific radiologic markers of CADASIL.
      METHODS: MRI scans from 20 consecutive patients with CADASIL and 20 patients with
      sporadic leukoaraiosis due to presumed small-vessel disease were compared using
      the previously validated semiquantitative MRI rating scale devised by Scheltens
      et al. Analysis was blinded to clinical category. RESULTS: Scores for
      hyperintensities of the temporal white matter and external capsule-insula region
      were significantly higher in patients with CADASIL. Hyperintensity confined to
      the pole of the temporal lobe was a characteristic finding in CADASIL, occurring
      in 19 patients with CADASIL but no patients with ischemic leukoaraiosis.
      Involvement of the external capsule, though less specific, was seen early in the
      disease course. In a few patients with CADASIL, involvement of the corpus
      callosum was observed. CONCLUSIONS: Temporal pole hyperintensity is a radiologic
      marker of CADASIL. Involvement of the external capsule and corpus callosum are
      also characteristic findings that may help to distinguish the disease.

PMID- 11245716
TI  - Altered white and gray matter metabolism in CADASIL: a proton MR spectroscopy and
      1H-MRSI study.
AB  - OBJECTIVE: Subcortical white matter hyperintensities (WMH) and small cystic
      lesions are the radiologic hallmark of cerebral autosomal dominant arteriopathy
      with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary
      angiopathy causing stroke in young adults. To further characterize the cerebral
      pathology in vivo we analyzed metabolite concentrations in normal and abnormal
      appearing brain tissue using single and multiple voxel proton MR spectroscopy (1H
      MRS and 1H-MRSI). METHODS: Twenty patients with CADASIL and 21 age-matched
      controls were studied with 1H-MRSI at the level of the centrum semiovale; short
      echo time 1H-MRS was performed in six patients (WMH) and 10 controls. LCModel
      fits were used to estimate absolute and relative concentrations of N:
      acetylaspartate (NAA), choline-containing compounds (Cho), total creatine (Cr)
      within WMH, normal appearing white matter (NAWM), and cortical gray matter (GM)
      as well as myo-inositol (mI) and lactate in WMH. RESULTS: 1H-MRSI-Patients with
      CADASIL showed significantly reduced NAA, Cho, Cr, and total metabolite content
      (Met(tot)) in WMH and NAWM. Normalization to Met(tot) revealed that NAA/Met(tot)
      was reduced in all regions, whereas Cho and Cr were relatively elevated in WMH.
      Short echo time 1H-MRS showed decreased NAA, Cr, Met(tot), and NAA/Met(tot) and
      elevated mI/Met(tot) and lactate in WMH. Metabolite changes were larger in
      severely affected subjects. Rankin scores correlated negatively with NAA/Met(tot)
      (all regions) and NAA/Cho (WMH), and positively with Cho/Met(tot) (WMH) and
      Cr/Met(tot) (NAWM). CONCLUSION: Marked metabolic abnormalities were observed in
      abnormal and normal appearing white matter in patients with CADASIL. The findings
      suggest axonal injury, enlarged extracellular spaces, myelin loss, and gliosis.
      The cortical abnormalities may reflect structural damage or functional neuronal
      impairment secondary to white matter pathology. NAA reductions were correlated
      with clinical disability emphasizing the clinicopathologic relevance of axonal
      injury in CADASIL.

PMID- 11245717
TI  - Occipital hypoperfusion on SPECT in dementia with Lewy bodies but not AD.
AB  - OBJECTIVE: To compare regional cerebral blood flow (rCBF) changes using 99mTc
      hexamethylpropyleneamine oxime (99mTc-HMPAO) SPECT in subjects with dementia with
      Lewy bodies (DLB) and AD and in normal age-matched control subjects; to examine
      the utility of SPECT changes in the differential diagnosis of AD and DLB. METHOD:
      Whole-brain SPECT scans were acquired using a single-headed rotating gamma camera
      (IGE CamStar XR/T) in elderly subjects with consensus criteria DLB (n = 23; mean
      age = 79.4 years), National Institute of Neurological and Communicative Disorders
      and Stroke-Alzheimer's Disease and Related Disorders Association AD (n = 50; 81.9
      years), and normal control subjects (n = 20; 78.1 years) after injection with 500
      MBq of 99mTc-HMPAO. Region-of-interest analysis was performed using a SPECT
      template registered in Talairach space, with rCBF normalized to cerebellum.
      RESULTS: Both DLB and AD subjects had significantly reduced rCBF in parietal and
      temporal regions compared with the control subjects. The AD group also showed a
      significant reduction in rCBF in the frontal and medial temporal regions and the
      DLB in the occipital areas compared with control subjects. AD and DLB groups
      differed only in occipital perfusion (p < 0.01). SPECT measures (occipital and
      medial temporal) correctly classified 69% of all subjects, with a 65% sensitivity
      and 87% specificity for DLB against AD and control subjects. CONCLUSION:
      Temporoparietal hypoperfusion on SPECT is common to both AD and DLB. Occipital
      hypoperfusion is more frequently seen in DLB. Although not diagnostically
      specific in individual cases, occipital hypoperfusion on SPECT should raise
      suspicion that DLB may be the cause of dementia, prompting careful search for
      other features of the disorder.

PMID- 11245718
TI  - Gender differences in predictors of mortality in nursing home residents with AD.
AB  - OBJECTIVE: To evaluate whether the excess mortality in men with AD can be
      explained by a gender difference in the predictors of mortality. METHODS: The
      authors studied 2,838 men and 6,385 women over 65 years of age with AD admitted,
      between 1992 and 1995, to 1 of nearly 1,500 nursing homes in five U.S. states
      (Kansas, Maine, Mississippi, New York, and South Dakota). Resident level data
      including sociodemographic characteristics, dementia severity, measures of
      physical disability, comorbidity, and other clinical variables were collected
      with the Minimum Data Set. Information on death was derived through linkage to
      Medicare enrollment files; the median follow-up was 23 months. Baseline
      characteristics were used to predict age at time of death in Cox proportional
      hazard models. RESULTS: Men with AD had an increased risk of mortality relative
      to women, adjusted for differences in the distribution of age and race. The most
      important predictors of death in men were those related to the disease itself.
      These were the severity of dementia and the occurrence of episodes of delirium.
      Instead, death among women was associated with measures of disability, namely,
      impairment in performing the activities of daily living, presence of pressure
      sores, malnutrition, and comorbidity. CONCLUSION: These data suggest that the
      underlying mechanisms for AD may be different in men and women. Future studies of
      survival and progression of AD need to examine men and women separately.

PMID- 11245720
TI  - Reversible pontine edema in hypertension.

PMID- 11245719
TI  - APOE-epsilon4 is associated with weight loss in women with AD: a population-based
      study.
AB  - OBJECTIVE: To investigate whether the APOE-epsilon4 allele is associated with
      weight loss in patients with AD or in nondemented elderly subjects. BACKGROUND:
      Weight loss has been considered a typical feature of AD. APOE-epsilon4 is a risk
      factor for AD and was recently proposed to be associated with weight loss in
      elderly women. It is not known whether APOE-epsilon4 is associated with weight
      loss in patients with AD or in the general population. METHODS: Weight and BMI
      measurements at an average interval of 3.5 years and APOE phenotype determination
      were performed in an elderly population (n = 980), including 46 patients with AD
      and 911 control subjects at the end of the follow-up. RESULTS: On average,
      patients with AD with the epsilon4 allele lost 1.9 +/- 4.0 kg (BMI 0.8 +/- 1.8
      kg/m2) whereas epsilon4 noncarriers gained 1.2 +/- 3.8 kg (BMI 0.4 +/- 1.5 kg/m2)
      (both p < 0.05), after controlling for diabetes and exercise. However, when men
      and women were analyzed separately, weight loss was observed only in those women
      with AD with the epsilon4 allele. Clinically significant weight loss, defined as
      loss of > or = 5% of body weight, occurred more frequently in both patients with
      AD (30% versus 6%; p < 0.05) and control subjects (28% versus 18%; p < 0.001)
      carrying the epsilon4 allele. CONCLUSIONS: The APOE-epsilon4 allele may
      contribute to the unexplained weight loss in AD, especially in women.

PMID- 11245721
TI  - Calpain-3 and dysferlin protein screening in patients with limb-girdle dystrophy
      and myopathy.
AB  - BACKGROUND: Mutations in the genes encoding for calpain-3 and dysferlin are
      responsible for limb-girdle muscular dystrophy (LGMD) type 2A and 2B, the most
      common forms of autosomal recessive LGMD. OBJECTIVE: To identify calpain-3 or
      dysferlin deficiency in a large cohort of patients with as yet unclassified LGMD
      and myopathy through candidate protein analysis. METHODS: The authors' muscle
      biopsy database search identified 407 candidate muscle biopsies with normal
      dystrophin and sarcoglycan. Calpain-3 and dysferlin were studied by Western
      blotting and immunohistochemistry. RESULTS: Combined calpain-3 and dysferlin
      Western blot analysis identified calpain-3 deficiency in 66 (16%) muscle
      biopsies. In 31 cases (47%), the protein was absent, and in 35 (53%), it was
      severely reduced in amount (3 to 50% of control). Dysferlin deficiency was found
      in 26 (6.5%) muscle biopsies. In 9, the protein was absent (35%), and in 17
      (65%), it was severely reduced in amount (traces to 20% of control). Twenty-eight
      percent (53/191) of patients with LGMD phenotype had calpain-3 deficiency. Sixty
      percent (21/35) of patients with distal myopathy had dysferlin deficiency.
      Dysferlin immunohistochemistry showed, in the completely dysferlin-deficient
      patients, absent reaction at the sarcolemma but positive nuclear membrane
      labeling and, in the partially dysferlin-deficient patients, scattered granular
      positive cytoplasmic areas and diffuse reaction in regenerating fibers.
      CONCLUSION: About 25% of previously unclassified dystrophy/myopathy cases are due
      to calpain-3 or dysferlin protein deficiency. These results suggest that
      immunoblot analysis may be used to define patients for calpain-3 and dysferlin
      gene mutation studies.

PMID- 11245722
TI  - Disappearing "face of the giant panda".

PMID- 11245723
TI  - Serum levels of tumor necrosis factor-alpha in chronic inflammatory demyelinating
      polyneuropathy.
AB  - BACKGROUND: Activated macrophages and T lymphocytes may play a role in the
      pathogenesis of chronic inflammatory demyelinating polyneuropathy (CIDP). Both
      cell types secrete tumor necrosis factor-alpha (TNFalpha), which has toxic
      effects on myelin and endothelial cells. METHODS: The serum concentration of
      TNFalpha was measured by ELISA and compared with clinical and
      electrophysiological profiles in 20 patients with CIDP. RESULTS: An increased
      serum level of TNFalpha was detected in 5 (25%) patients and was associated with
      subacute progression, severe neurologic disabilities, and symmetric weakness
      involving proximal as well as distal muscles. TNFalpha levels increased during
      the active phase in this subgroup of patients. The levels of TNFalpha correlated
      with the severity of demyelinating conduction abnormalities in the intermediate
      as well as distal nerve segments, suggesting demyelination diffusely distributed
      along the nerves. CONCLUSION: Circulating TNFalpha increases during the active
      phase in a subgroup of CIDP patients and may play a role in the pathogenesis of
      demyelination and the breakdown of the blood-nerve barrier in CIDP.

PMID- 11245724
TI  - Restoring blood pressure reperfused Wernicke's area and improved language.
AB  - Longitudinal clinical and imaging data from a patient who sustained a left
      frontal-temporal stroke with hypoperfusion of the adjacent Wernicke's area are
      reported. His language deficits were partially ameliorated by pharmacologically
      increasing his blood pressure, and were exacerbated when blood pressure dropped.
      There was a striking temporal and statistical correlation between mean arterial
      pressure and language accuracy. MR perfusion imaging showed that language gains
      were accompanied by improved perfusion of Wernicke's area when mean arterial
      pressure was increased.

PMID- 11245725
TI  - Aldosterone synthase (CYP11B2) gene polymorphism and cerebral white matter
      hyperintensities.
AB  - The association between aldosterone synthase (CYP11B2) gene polymorphism and
      white matter hyperintensities seen on cerebral MRI was studied in a population
      based sample of 829 individuals aged 63 to 75 years. The T allele was associated
      with the risk of severe white matter hyperintensities. Compared with the CC
      genotype, the adjusted OR for severe white matter hyperintensities was 4.61 (95%
      CI, 1.46 to 14.55) for the TT genotype and 2.45 (95% CI, 0.81 to 7.46) for the TC
      genotype in men. This association was independent of hypertension.

PMID- 11245726
TI  - Evidence for genetic heterogeneity in hereditary neuralgic amyotrophy.
AB  - Hereditary neuralgic amyotrophy (HNA) is a rare autosomal dominant disorder
      characterized by recurrent episodes of severe arm and shoulder pain with
      weakness, atrophy, and sensory impairment in a brachial plexus distribution.
      Recent studies mapped the HNA locus to chromosome 17q25. Two pedigrees with
      clinically typical HNA in which markers from chromosome 17q25 do not cosegregate
      with the disease and in which lod scores do not support linkage to chromosome
      17q25 were identified.

PMID- 11245727
TI  - Chronic encephalitis and temporal lobe epilepsy: a variant of Rasmussen's
      syndrome?
AB  - The authors report two adult patients with chronic temporal lobe epilepsy and
      pathologic features consistent with Rasmussen's encephalitis. Although seizures
      persisted after temporal lobe surgery no progressive cognitive or neurologic
      deficit has emerged. Prominent auditory auras in each suggested a persisting
      epileptogenic focus in the superior temporal gyrus. The current findings expand
      the clinical spectrum of Rasmussen's encephalitis and suggest that chronic
      nonprogressive encephalitis may serve as the pathologic substrate of medically
      intractable temporal lobe epilepsy.

PMID- 11245728
TI  - Catathrenia (nocturnal groaning): a new type of parasomnia.
AB  - Four patients between 15 and 25 years of age presented with exclusively
      expiratory groaning during sleep. Groaning usually occurred during the second
      part of the night, beginning at age 5 to 16 years. Patients were unaware of the
      nocturnal noise, but it alarmed others. Results of otorhinolaryngologic and
      neurologic examinations were normal. Expiratory groaning arose during REM and non
      REM sleep stage 2, and was repeated in clusters. Nocturnal groaning, which the
      authors term catathrenia, represents a distinctive parasomnia.

PMID- 11245729
TI  - Continuous vertigo and spontaneous nystagmus due to canalolithiasis of the
      horizontal canal.
AB  - The authors present a patient with benign paroxysmal positional vertigo of the
      right horizontal semicircular canal who developed persistent vertigo with
      spontaneous horizontal nystagmus to the left and caloric hypoexcitability on the
      right after a head shaking maneuver. Both spontaneous nystagmus and canal paresis
      resolved after repeated shaking of the head. The most probable mechanism of this
      type of vertigo is plugging of the horizontal canal by otoconial particles with a
      negative endolymph pressure between plug and cupula.

PMID- 11245731
TI  - Treatment of ALS with pleconaril.

PMID- 11245730
TI  - The T9176G mtDNA mutation severely affects ATP production and results in Leigh
      syndrome.
AB  - The authors identified a novel mtDNA mutation (T9176G) in the ATPase 6 gene in a
      family in which a 10-year-old girl had a severe neurodegenerative disorder, her
      elder sister had died of Leigh syndrome (LS), and a maternal uncle had a
      spinocerebellar disorder. Biochemical studies disclosed a reduced rate of ATP
      synthesis in skin fibroblast cultures from the proposita as the likely
      explanation of her severe illness. The findings expand the genetic variants
      associated with LS.

PMID- 11245732
TI  - Normal calpain expression in genetically confirmed limb-girdle muscular dystrophy
      type 2A.

PMID- 11245733
TI  - Is Epstein-Barr virus present in the CNS of patients with MS?

PMID- 11245734
TI  - Chenodeoxycholic treatment of cerebrotendinous xanthomatosis.

PMID- 11245735
TI  - Practice parameter: risk of driving and Alzheimer's disease.

PMID- 11245736
TI  - AIDS-related focal brain lesions in the era of highly active antiretroviral
      therapy.

PMID- 11245737
TI  - Case-control study of leatherwork and male infertility.
AB  - OBJECTIVES: To test the hypothesis that leatherwork is associated with male
      infertility mediated through the development of oligozoospermia. The basis of any
      association was postulated, at the outset, to be with exposure to the solvents
      used in leatherwork. METHODS: All new referrals with infertility presenting in
      Leicestershire hospital clinics between November 1988 and September 1992 and
      Kettering District General Hospital from August 1990 were eligible to
      participate; 88.5% agreed to be interviewed. Exposure to leatherwork and work
      with solvents was defined by job title. Comparisons were made with fertile
      controls and in an analysis within men from infertile couples with
      oligozoospermia as the primary outcome. Effects on sperm motility and deformity
      were investigated secondarily. Analyses used logistic regression for binary
      outcomes and multilevel modelling for continuous outcomes. RESULTS: 1906 men were
      interviewed. Compared with the fertile controls the men from infertile couples
      were 1.10 times (95% confidence interval (95% CI) 0.46 to 2.63; p=0.99) more
      likely to be leatherworkers and 1.73 times (95% CI 1.26 to 2.38; p<0.001) more
      likely to work with solvents. Compared with other men, leatherworkers were 1.20
      times (95% CI 0.43 to 3.33; p=0.73) more likely to present with oligozoospermia
      and 1.65 times (95% CI 0.37 to 7.30; p=0.51) more likely to present with
      teratozoospermia. Being a leatherworker was associated with only a 6% reduction
      in sperm concentration; motility and deformity were similarly unaffected by this
      exposure. Work with solvents did not statistically, nor clinically, increase the
      risk of oligozoospermia, teratozoospermia, or asthenozoospermia. CONCLUSIONS:
      There was little evidence to support the hypothesis that leatherwork is
      associated with an increased risk of presenting with infertility or
      oligozoospermia. There was limited evidence that leatherwork is a risk factor for
      teratozoospermia. Workers with solvents were at an increased risk of presenting
      with infertility, although this was not mediated through effects on standard
      measures of semen quality; this finding merits further investigation.

PMID- 11245738
TI  - Solvent use and time to pregnancy among female personnel in biomedical
      laboratories in Sweden.
AB  - OBJECTIVES: To elucidate possible effects on fecundability from chemical,
      biological, and physical agents in laboratories, a retrospective study based on a
      questionnaire was conducted among female personnel who worked in Swedish
      biomedical research laboratories. Female personnel in non-laboratory departments
      were used as a reference group. The maximum number of women included in the
      analyses was 560. This corresponded to 2519 menstrual cycles. These women had
      given birth at least once during the period 1990-4. METHODS: Time to pregnancy
      was used to estimate the fecundability-that is, probability of conception of a
      clinically detectable pregnancy per cycle. The fecundability ratio (FR) between
      exposed and unexposed cycles was calculated with a discrete time analogue of the
      Cox's proportional-hazards model. The FR estimates below unity indicate
      subfecundity. RESULTS: Work with organic solvents in general in laboratory work,
      gave a decreased adjusted fecundability ratio (FR) of 0.79 (95% confidence
      interval (95 % CI) 0.68 to 0.93). Moreover, work with acetone and use of viruses
      also showed decreased FRs, 0.72 (0.53 to 0.97) and 0.66 (0.49 to 0.90),
      respectively. CONCLUSIONS: The results of the present study give some indications
      of reduced fecundability for work with specific agents in laboratories, and
      support previously reported findings of a negative influence of organic solvents
      on fecundity among female laboratory personnel.

PMID- 11245739
TI  - Public health response to an incident of secondary chemical contamination at a
      beach in the United Kingdom.
AB  - OBJECTIVES: To gather enough data from a large scale investigation involving two
      health authorities, to assess the possible concentrations and routes of exposure
      and the consequent health implications. To use the data to decide whether a
      polluted beach should remain open to the public. In Spring 1997, a chemical
      incident came to light at a beach on the south coast of England when a local
      resident reported a sulphurous smell, visible signs of oil, and reduced numbers
      of fishing bait. The beach was situated adjacent to a former gasworks site and
      was accessible to the public. The incident was reported to the local authority
      and was initially investigated by the Environment Agency and the local authority.
      An Environment Agency report confirmed contamination of the beach with cyanide,
      ammonia, and polycyclic aromatic hydrocarbons (PAHs) with associated potential
      health risks. The incident was then referred to the local health authorities for
      investigation. METHODS: The investigation was carried out in four stages:
      comprehensive sampling and analysis to identify the extent of contamination,
      followed by an assessment of risk to health; establishment of a long term
      monitoring programme to identify any changes in contaminant concentrations;
      investigation of the effects of the contamination on shellfish; and review of the
      routine monitoring data and current sampling strategy. RESULTS: The initial
      investigation confirmed that the beach was contaminated, with the most likely
      source being the adjacent former gasworks site. The level of contamination was
      not found to be likely to pose a hazard to users of the beach. However,
      subsequent investigation of shellfish in the area led to warning signs being
      erected on the beach to prevent human consumption of mussels contaminated with
      PAHs. CONCLUSIONS: Several lessons can be learnt from this investigation, which
      can be applied to incident management more generally: the importance of
      collaboration and coordination; the need for early involvement of the health
      authority; and the importance of carrying out appropriate sampling and analysis
      as soon as possible, to assess the risk to health and the environment.

PMID- 11245740
TI  - Cross sectional and longitudinal study on selenium, glutathione peroxidase,
      smoking, and occupational exposure in coal miners.
AB  - OBJECTIVES: To understand the variations of selenium (Se) concentration relative
      to changes in occupational exposure to coal dust, taking into account age and
      changes in smoking habits in miners surveyed twice, in 1990 and 1994. To better
      understand the relation of Se concentration with glutathione peroxidase
      activities (GSH-Px) in these miners. METHODS: In 1994, blood samples were
      obtained from active (n=131) and retired (n=40) miners without coal worker's
      pneumoconiosis, in whom Se concentration was available at both surveys and in
      whom International Labour Organisation (ILO) profusion grade had not been
      changed. Active miners were exposed to high dust concentrations (n=48) or low
      dust concentrations (n=83). Miners were classified into three subgroups according
      to their estimated cumulative exposure to dust, and into three subgroups
      according to their smoking habits. RESULTS: Selenium concentration and GSH-Px
      activities were significantly lower in active than in retired miners (Se adjusted
      means: 62.6 v 72.2 ng/ml p=0.01). Moreover, Se concentration was lower in miners
      exposed to high compared with those exposed to low dust concentrations (adjusted
      means: 59.4 v 65.8). In miners exposed to high dust concentrations, Se
      concentration was significantly lower whereas erythrocyte GSH-Px activity was
      significantly higher in the subgroup with estimated cumulative exposure >68
      mg/m(3).y. In all miners, plasma GSH-Px activity was correlated with Se
      concentration (r=0.22, p<0.005). The 4 year Se changes were negatively related to
      exposure to high dust concentrations and positively related to change in exposure
      from high to retirement and to change from smoker to ex-smoker (p=0.01).
      CONCLUSION: The variations of Se concentration in relation to changes in
      occupational exposure to coal dust and in smoking habits, and the close
      correlation found between plasma Se concentration and GSH-Px activity suggest
      that both are required in antioxidant defence. These results agree well with the
      hypothesis that the decrease in Se concentration reflects its use against
      reactive oxygen species generated by exposure to coal mine dust and by smoking.

PMID- 11245741
TI  - Prognostic factors for respiratory sickness absence and return to work among blue
      collar workers and office personnel.
AB  - OBJECTIVES: To analyze factors that determine the occurrence of sickness absence
      due to respiratory disorders and the time it takes to return to work. METHODS: A
      longitudinal study with 2 year follow up was conducted among 326 male blue collar
      and white collar workers. The survey started with an interview on respiratory
      complaints and spirometry. Sixty six (21%) workers were lost to follow up.
      Complete data on sickness absence among 251 workers during the follow up were
      collected from absence records and self reports. Regression analysis based on a
      proportional hazards model was applied to identify risk factors for the
      occurrence and duration of sickness absence due to respiratory disorders.
      RESULTS: During the follow up 35% workers attributed at least one period of
      sickness absence to respiratory complaints, which accounted for 14.2% of all days
      lost. A history of chronic obstructive pulmonary disease (COPD) did not predict
      sickness absence for COPD; the same was true for chronic non-specific lung
      disease (CNSLD). Complaints about asthma contributed significantly to absence due
      to asthma (relative risk (RR) 3.96; 95% confidence interval (95% CI) 1.99 to
      7.90). Job title was a significant predictor of sickness absence due to
      respiratory complaints. Decrease in forced vital capacity (FVC, <80% of the
      reference value) was also a significant predictor of absence due to asthma (RR
      4.03; 95% CI 1.41 to 11.54) and of respiratory absence (RR 2.49; 95% CI 1.07 to
      5.79). Absence with respiratory complaints was not associated with age, height,
      body mass index, or smoking. Duration of employment was a weak almost significant
      predictor against respiratory absenteeism (RR 0.94; 95% CI 0.91 to 0.97). Return
      to work after respiratory absence was worse for blue collar workers than office
      personnel (RR 5.74; 95% CI 1.90 to 17.4 for welders, and RR 6.43; 95% CI 2.08 to
      19.85 for metal workers). CONCLUSIONS: Asthmatic complaints in the 12 months
      before the study were associated with sickness absence for these complaints
      during the follow up. An abnormal level of FVC also influenced respiratory
      absenteeism. Blue collar workers had more often and more prolonged absences due
      to respiratory disorders than white collar workers. Workers with absence due to
      respiratory complaints were at higher risk of subsequent sickness absence in the
      next year.

PMID- 11245742
TI  - Hospital admissions among male drivers in Denmark.
AB  - OBJECTIVES: To facilitate decisions about interventions and to establish baseline
      values for future evaluation of preventive efforts, the aim of the present study
      was to elucidate the disease pattern among male professional drivers in Denmark.
      The study differentiated between drivers of goods vehicles and drivers of
      passenger transport. METHODS: Cohorts of all 20-59 year old Danish male
      professional drivers in the years 1981, 1986, 1991, and 1994 were formed, to
      calculate age standardised hospital admission ratios (SHRs) and time trends (1981
      97) for many diagnostic aggregations. RESULTS: SHRs for diseases in practically
      all systems and organs of the body were higher among professional drivers than
      they were in the male working population at large. Also drivers of passenger
      transport, compared with drivers of goods vehicles, had significantly high SHRs
      due to infectious and parasitic diseases, diseases of the circulatory system, and
      diseases of the respiratory system, and significantly lower rates of injury. For
      both driver groups, the SHRs for acute myocardial infarction increased with time
      whereas the SHR for acute gastritis decreased, and for drivers of passenger
      transport an increasing SHR for chronic obstructive pulmonary disease, was found
      over time. CONCLUSION: Drivers of passenger transport and drivers of goods
      vehicles differ in their disease patterns. The results support the hypothesis
      that preventive efforts are needed in both groups, but underline that different
      strategies are required for different categories of drivers.

PMID- 11245743
TI  - Erionite bodies and fibres in bronchoalveolar lavage fluid (BALF) of residents
      from Tuzkoy, Cappadocia, Turkey.
AB  - OBJECTIVES: The high incidence of malignant mesothelioma in some villages of
      Cappadocia (Turkey) is due to environmental exposure to erionite fibres. The aim
      was to evaluate the fibre burden in bronchoalveolar lavage fluid (BALF) from
      inhabitants of an erionite village and compare it with Turkish subjects with or
      without environmental exposure to tremolite asbestos. METHODS: Ferruginous bodies
      (FBs) and fibres were measured and analyzed by light and transmission electron
      microscopy (TEM) in the BALF of 16 subjects originating from Tuzkoy. RESULTS: FBs
      were detected in the BALF of 12 subjects, with concentrations above 1 FB/ml in
      seven of them. Erionite was the central fibre of 95.7% of FBs. Erionite fibres
      were found in the BALF of all subjects, by TEM, and these fibres were low in Mg,
      K, and Ca compared with erionite from Tuzkoy soil. The mean concentration of
      erionite fibres in BALF was similar to that of tremolite fibres in Turks with
      environmental exposure to tremolite. The proportion of fibres longer than 8
      microm in BALF represented 35.6% for erionite compared with 14.0% for tremolite.
      The asbestos fibre concentrations in erionite villagers was not different from
      that in Turks without environmental exposure to tremolite. CONCLUSION: Analysis
      of BALF gives information about fibre retention in populations environmentally
      exposed to erionite for whom data on fibre burden from lung tissue samples are
      scarce. This may apply to exposed Turks having emigrated to other countries.

PMID- 11245744
TI  - Psychological factors and visual fatigue in working with video display terminals.
AB  - OBJECTIVES: To examine the part played by psychological factors in complaints
      about visual health reported by banking officers who work at video display
      terminals (VDTs). METHODS: Out of a population of 385 bank workers, a group of
      212 subjects without organic visual disturbances (as determined by
      ophthalmological examination) who share a work environment and job duties was
      selected. Three questionnaires were administered to these subjects: (a) the NIOSH
      job stress questionnaire; (b) a questionnaire investigating subjective discomfort
      related to environmental and lighting conditions of the workplace; (c) a
      questionnaire on the existence of oculovisual disturbances. Correlation and
      multiple regression analyses were performed to examine for the presence of
      predictors of asthenopia. RESULTS: Social support, group conflict, self esteem,
      work satisfaction, and underuse of skills were found to be predictors of visual
      complaints; social support played a part also as a moderating factor in the
      stress and strain model; this model accounted for 30% of the variance. Subjective
      environmental factors, although in some cases significantly correlated with
      asthenopia, were not found to be strong predictors of the symptoms. CONCLUSIONS:
      Some part of the complaints about visual health reported by VDT workers are
      likely indirect expressions of psychological discomfort related to working
      conditions.

PMID- 11245745
TI  - Consumer satisfaction with occupational health services: should it be measured?
AB  - OBJECTIVES: To find answers in the literature to the questions if, why, and how
      consumer satisfaction with occupational health services (OHSs) should be
      measured. METHODS: Publications about the concept of consumer satisfaction with
      health care and surveys of consumer satisfaction with occupational health care
      were reviewed. RESULTS: For care providers, surveys of consumer satisfaction can
      be useful to improve quality or as indicators of non-compliant behaviour among
      patients. For clients, satisfaction surveys can be helpful for choosing between
      healthcare providers. Satisfaction is made up of an affective component of
      evaluation and a cognitive component of expectations. Also, in occupational
      health care, patient satisfaction is measured by dimensions such as the humanness
      and competence of the care provider similar to health care in general. However,
      there are dimensions that are specific to occupational health-such as the
      perceived independence of the physician, unclear reasons for visiting an OHS, and
      the perceived extent of knowledge of OHS professionals about the patient's
      working conditions. Dimensions of client satisfaction are mostly similar to
      patient satisfaction but include more businesslike aspects. They are different
      for the two groups of client, employers and employees. To measure consumer
      satisfaction in occupational healthcare specific questionnaires must be
      constructed. To achieve the highest possible reader satisfaction guidelines are
      provided for construction of a questionnaire. CONCLUSIONS: Consumer satisfaction
      is a complex theoretical concept, but it is relatively easy to measure in
      practice and can be a valuable tool for quality improvement. Consumers'
      evaluations of occupational health services will become increasingly important
      due to changes in the organisation of occupational health care. Occupational
      healthcare providers are encouraged to measure the consumer satisfaction of their
      services.

PMID- 11245748
TI  - Rehabilitation medicine: coming together in partnership.

PMID- 11245747
TI  - Are problems with male reproductive health caused by endocrine disruption?

PMID- 11245749
TI  - Outcome after traumatic brain injury: pathway analysis of contributions from
      premorbid, injury severity, and recovery variables.
AB  - OBJECTIVE: To examine the relationship of premorbid variables, injury severity,
      and cognitive and functional status to outcome 1 year after traumatic brain
      injury (TBI) and to assess the feasibility of multivariate path analysis as a way
      to discover those relationships. DESIGN: Prospective, longitudinal. SETTINGS:
      Level I trauma center, acute inpatient rehabilitation hospital. PATIENTS: One
      hundred seven subjects (87 men, 20 women; mean age, 33.91 +/- 14.2 yr) who had
      experienced severe TBI, typically from motor vehicle crashes. INTERVENTIONS:
      Acute medical and rehabilitation care. MAIN OUTCOME MEASURES: Disability Rating
      Scale, Community Integration Questionnaire, and return to employment. Evaluated
      in acute rehabilitation, and at 6 and 12 months' postinjury. RESULTS: Path
      analyses revealed that premorbid factors had significant relationships with
      injury severity, functional skills, cognitive status, and outcome; injury
      severity affected cognitive and functional skills; and cognitive status
      influenced outcome. No significant relationships were found between injury
      severity and emotional status, injury severity and outcome, emotional status and
      outcome, and functional skills and outcome. CONCLUSIONS: Multivariate analysis is
      important to understanding outcome after TBI. Injury severity, as measured in
      this study, is less important to 12-month outcome than the premorbid status of
      the person and the difficulties (particularly cognitive deficits) exhibited at
      follow-up 6 months after the trauma.

PMID- 11245750
TI  - Severe penetrating head injury: a study of outcomes.
AB  - OBJECTIVE: To determine and describe the demographics and functional outcomes of
      persons who require inpatient rehabilitation for severe penetrating head injury
      resulting from a gunshot wound to the head. DESIGN: Data were collected
      prospectively from the time of admission to acute care through discharge from
      inpatient rehabilitation. SETTING: Two sites: an urban, level I, acute care,
      trauma center and an inpatient rehabilitation hospital with a specialized brain
      injury unit. PARTICIPANTS: Twenty-seven persons with severe penetrating head
      injury. MAIN OUTCOME MEASURES: The FIM instrument, the Disability Rating Scale
      (DRS), and the length of stay (LOS). RESULTS: Demographic data showed our
      population to be similar to other groups of persons at high risk for violent
      injury. Eighty-five percent of the subjects were men with a mean age of 34 years.
      The majority were African American (93%), reflective of our general patient
      population. Average acute care LOS was 31 days and average rehabilitation LOS was
      44 days. Average FIM gain was 40.2 and, on average, DRS scores improved 7.6
      points from rehabilitation admission to discharge. All study participants made
      enough progress to be discharged to private residences. CONCLUSION: Although the
      mortality rate is high among patients with penetrating head injury, those who
      survive to receive inpatient rehabilitation can achieve functional improvement.

PMID- 11245751
TI  - Positive outcomes in traumatic brain injury-vegetative state: patients treated
      with bromocriptine.
AB  - OBJECTIVE: To assess the effects of multidisciplinary rehabilitation
      interventions and use of bromocriptine on outcome in patients with traumatic
      brain injury-vegetative state (TBI-VS). DESIGN: Retrospective review of clinical
      cases. SETTING: Free-standing rehabilitation hospital; Acute and extended
      rehabilitation hospital. PARTICIPANTS: Five consecutive TBI-VS patients, as well
      as 33 TBI-VS patients and 37 traumatic brain injury-minimally conscious state
      (TBI-MCS) patients reported in the literature. INTERVENTIONS: Bromocriptine
      administration, systematic neuropsychologic testing, sensory stimulation, and
      traditional comprehensive rehabilitation with physical therapy, occupational
      therapy, and speech therapy. MAIN OUTCOME MEASURES: Disability Rating Scale (DRS)
      at 1, 3, 6, and 12 months postinjury and FIM instrument scores at 1 month and 12
      months postinjury, Coma Recovery Scale, and Barry Rehabilitation Inpatient
      Screening of Cognition. RESULTS: The 5 TBI-VS patients emerged from a VS into a
      MCS and regained functional status. Their recovery of physical and cognitive
      functioning, as rated by the DRS, was greater than previously reported in the
      literature for patients in a VS or MCS at 3, 6, and 12 months postinjury.
      CONCLUSION: Bromocriptine administration, systematic neuropsychologic testing,
      sensory stimulation, a comprehensive rehabilitation program, or a combination of
      these treatments may enhance functional recovery in this TBI-VS patient group.
      Further systematic study to quantify the contribution of these variables and to
      reproduce this data in a larger patient population should be performed.

PMID- 11245752
TI  - Sleep apnea in adults with traumatic brain injury: a preliminary investigation.
AB  - OBJECTIVE: To determine the occurrence and nature of sleep-related breathing
      disorders in adults with traumatic brain injury (TBI). DESIGN: Prospective,
      observational, consecutive sample enrollment of subjects admitted for
      rehabilitation after TBI. SETTING: Inpatient rehabilitation and subacute
      rehabilitation units of a tertiary care university medical system. PARTICIPANTS:
      Subjects (n = 28) included adults with TBI and a Rancho Los Amigos Scale level of
      3 or greater who were less than 3 months postinjury and admitted for
      comprehensive inpatient rehabilitation. INTERVENTIONS: Overnight sleep study
      using portable 6-channel monitoring system. MAIN OUTCOME MEASURE: Respiratory
      disturbance index (RDI), which is the number of apneic and hypopneic episodes per
      hour of sleep. RESULTS: Evidence of sleep apnea was found in 10 of 28 (36%)
      subjects as measured by a RDI level of 5 or greater and in 3 of 28 (11%) subjects
      as measured by a RDI level of 10 or greater. This rate of sleep apnea is
      significantly (p =.002) higher than would be predicted based on population norms.
      No correlation was found between the occurrence of significant sleep apnea and
      measures of TBI severity or other demographic variables. Sleep-related breathing
      disorders were primarily central though obstructive apneas were also noted.
      CONCLUSION: In this preliminary investigation, sleep-related breathing disorders
      as defined by a respiratory disturbance index of 5 or greater appears to be
      common in adult subjects with TBI.

PMID- 11245753
TI  - Recovery of functional status after right hemisphere stroke: relationship with
      unilateral neglect.
AB  - OBJECTIVE: To evaluate relationships between unilateral spatial neglect and both
      overall and cognitive-communicative functional outcomes in patients with right
      hemisphere stroke. DESIGN: Assessment of overall and cognitive-communicative
      function was conducted on admission to acute rehabilitation, at discharge, and at
      3-month follow-up. SETTING: Urban, acute inpatient rehabilitation facility.
      PATIENTS: Fifty-two consecutive admissions of adult right-handed patients with a
      single, right hemispheric stroke, confirmed by computed tomography scan. MAIN
      OUTCOME MEASURES: The FIM instrument and reading comprehension and written
      expression items of the Rehabilitation Institute of Chicago Functional Assessment
      Scale(R). RESULTS: Patients made significant functional gains between admission
      and discharge, and between discharge and follow-up on the FIM. Severity of
      neglect was correlated with total, motor, and cognitive FIM scores at admission,
      discharge, and follow-up. Subjects with neglect had significantly more days from
      onset to admission and a longer length of rehabilitation stay than subjects
      without neglect. FIM outcomes were significantly different for subject groups
      with more severe neglect. Both the presence of neglect and its severity were
      significantly related to functional outcomes for reading and writing.
      CONCLUSIONS: Patients with neglect show reduced overall and cognitive
      communicative functional performance and outcome than patients without neglect.
      Further studies are needed to explore causal relationships between these factors.

PMID- 11245754
TI  - Hierarchical linear modeling of FIM instrument growth curve characteristics after
      spinal cord injury.
AB  - OBJECTIVE: To examine the recovery of aspects of functional independence as a
      continuous process using growth curve analysis. DESIGN: Retrospective database
      review of functional outcome assessment data from inception cohort. SETTING:
      Inpatient rehabilitation unit; community. PATIENTS: A total of 142 subjects
      (79.6% men; age range, 18-77yr; mean age +/- standard deviation, 36.2 +/- 15.5yr)
      who were admitted to a rehabilitation unit between March 1986 and November 1994
      with a minimum of 4 postinjury FIM assessments. Neurologic subgroups included 63
      individuals with paraplegia, 36 with low tetraplegia, 24 with high tetraplegia,
      and 19 with incomplete injury. MAIN OUTCOME MEASURE: FIM instrument. RESULTS:
      Growth curve analyses with hierarchical linear modeling using a decelerating
      recovery function yielded a reliable model in which longer rehabilitation length
      of stay was associated with a more rapid rate of recovery but lower plateau.
      Neurologic injury category had expected effects on rate and degree of recovery.
      Level of impairment-specific results included an age effect in which older age
      was associated with lower level of plateau. In specific neurologic groups there
      was a significant gender effect, in which men made more rapid recovery than
      women, and a significant effect of level of education, in which higher education
      was associated with more rapid rate of recovery. Rate of FIM recovery was
      reliably modeled in the sample with incomplete injuries, but none of the
      demographic predictors was significant. CONCLUSIONS: Functional recovery can be
      modeled as a decelerating rather than simple linear function. The study of
      predictors of recovery characteristics, including rate of recovery and plateau,
      offers a valuable way of understanding rehabilitative needs and outcomes. Gender
      and education effects on the recovery process are intriguing and warrant further
      investigation.

PMID- 11245755
TI  - Pulmonary function and spinal characteristics: their relationships in persons
      with idiopathic and postpoliomyelitic scoliosis.
AB  - OBJECTIVE: To identify what influence the various features of spinal deformity
      have on pulmonary function in persons with idiopathic and the postpoliomyelitic
      scoliosis. DESIGN: Prospective, cohort, observational study with clinical and
      radiologic evaluations. SETTING: Hospital-based rehabilitation units. PATIENTS:
      Forty-four patients with idiopathic scoliotis and 16 with postpoliomyelitic
      scoliotis. Each group was divided into subgroups: normal and abnormal pulmonary
      function. INTERVENTION: Clinical and radiologic evaluation of spinal deformity,
      full pulmonary functional test and respiratory muscle strength were performed.
      Presence of dyspnea on exertion and low back pain (LBP) was recorded. MAIN
      OUTCOME MEASURES: Pulmonary function: spirometry, lung volume test, and diffusing
      capacity. Respiratory muscle strength: maximal inspiratory pressure (MIP) and
      maximal expiratory pressure (MEP). Presence of dyspnea on exertion (DOE), and LBP
      were also recorded. Characteristics of spinal deformity: direction of convexity,
      uppermost vertebra, number of involved vertebrae, Cobb angle, the apical
      vertebra, degree of rotation at the apical vertebra, type of scoliotic curve, and
      presence of balanced spine and pelvic obliquity. Chi-square analyses and Mann
      Whitney U test for between-groups comparisons. Spearman's rho correlation
      coefficient to determine the existence and magnitude of a relationship. RESULTS:
      We found significant differences between the idiopathic and postpoliomyelitis
      groups in the degree of rotation at the apical vertebra, MIP, average percentage
      of predicted vital capacity, residual volume/total lung capacity, presence of
      double or triple curves, pelvic obliquity, and DOE. Between the idiopathic
      scoliotis subgroups we found significant differences in the uppermost vertebra
      and number of vertebrae in the scoliotic curve. Between the subgroups of the
      postpoliomyelitis group were significant differences in the location of the
      apical vertebra and the uppermost vertebral body of scoliotic curve. In the
      idiopathic group, pulmonary function was mostly related to scoliotic angle,
      number of vertebrae in the scoliotic curve, location of the uppermost vertebra,
      and the patients' age; MIP and MEP were negatively related to the scoliotic angle
      and degree of rotation of apical vertebra. In the postpoliomyelitis group,
      pulmonary function was mostly related to scoliotic angle, kyphotic angle,
      location of the uppermost vertebra of the scoliotic curve, and age. CONCLUSION:
      No single factor can predict the severity of impairment in scoliotic patients'
      pulmonary function. In both groups, severity of pulmonary impairment was related
      to the combined features of the spinal deformity. However, uppermost vertebra,
      scoliotic angle, and patient's age may play important roles influencing pulmonary
      function in both groups.

PMID- 11245756
TI  - The reversal of antagonists facilitates the peak rate of tension development.
AB  - OBJECTIVE: The present study was designed to test the effects of the reversal of
      antagonists on the peak rate of tension development (dF/dt(max)) of the elbow
      extensors. DESIGN: Experimental, with matched controls. SETTING: A biomechanics
      research laboratory. PARTICIPANTS: Twenty-six healthy women without a history of
      upper extremity injury or neurologic disorder, randomly assigned to experimental
      (n = 13) or control (n = 13) groups. INTERVENTIONS: Two groups of healthy
      subjects followed identical exercise protocols, except that the control group
      performed maximal isometric contractions of the elbow extensors and the
      experimental group executed a maximal isometric elbow flexion contraction
      immediately before a maximal elbow extension contraction. Both groups performed 5
      cycles of a 2-second contraction with 22-second rest periods between agonist
      muscle contractions and were evaluated at 4 test sessions spaced 2 weeks apart.
      MAIN OUTCOME MEASURES: All measurements were done with the shoulder and elbow at
      90 degrees of flexion in the sagittal plane to ensure reproducibility. A load
      cell was used to measure elbow extension moment and to calculate the peak rate of
      tension development (dF/dt(max)). Biceps and triceps brachii surface
      electromyographic activity was monitored concurrently. The electromyographic
      measures were mean spike (peak-to-peak) amplitude and mean spike frequency of the
      biceps and triceps brachii activity. RESULTS: Intraclass dF/dt(max) and
      electromyographic reliability was good (r > or = .72) in both groups. Because
      biceps electromyographic measures were considerably less reliable (r < or = .53),
      they were not included in our analysis. While dF/dt(max) increased quadratically
      in both groups (p <.05), the experimental group was on average 36.1Nm. s(-1)
      (63%) greater across sessions 2 to 4 (p <.05). In contrast, triceps
      electromyographic activity did not differ significantly between groups (p >.05).
      The means averaged across groups exhibited a quadratic increase from session 1 to
      session 4: 91microV or 48% for mean spike amplitude (p <.05) and 7Hz or 16% for
      mean spike frequency (p <.05). CONCLUSIONS: The greater dF/dt(max) for the
      experimental group was not associated with increased electromyographic activity.
      The experimental group appeared to use the biomechanic properties of the
      pretensioned extensor muscle-tendon complex, rather than neurologic biasing, to
      accomplish its power gains.

PMID- 11245757
TI  - Benefits of an inpatient pulmonary rehabilitation program: a prospective
      analysis.
AB  - OBJECTIVE: To examine the effect of an inpatient pulmonary rehabilitation program
      on functional outcome, supplemental oxygen use, quality of life (QOL), and
      rehospitalization. DESIGN: A prospective study. SETTING: Inpatient pulmonary
      rehabilitation unit. PATIENTS: One hundred fifty-seven patients with moderate to
      severe chronic obstructive pulmonary disease (COPD) admitted to an inpatient
      pulmonary rehabilitation program over a 3-year period. INTERVENTION:
      Comprehensive interdisciplinary inpatient pulmonary rehabilitation program with
      an average length of stay of 21 days. MAIN OUTCOME MEASURES: Improvements in QOL
      questionnaire scores, COPD knowledge questionnaire scores, 6-minute walking test
      (with 3 ambulation categories: bed-bound, household ambulators, community
      ambulators), and supplemental oxygen use. Rehospitalization 1 year after
      completion of the program was also assessed and compared with hospital days for
      the year before the program. RESULTS: On discharge from the program, 88% of
      individuals walked farther (p <.0001), and community ambulators doubled their
      walking distance, whereas bed-bound patients decreased 10-fold; supplemental
      oxygen use dropped 33% during the day (p <.0001) and 57% during the night (p
      <.0001); 82% showed improved QOL (p <.0001); 67% showed improved knowledge of
      COPD (p <.0001); and 67% of the sample spent less time in the hospital during the
      12 months after program completion compared with the 12 months before admission
      (p <.001). CONCLUSIONS: An inpatient pulmonary rehabilitation program leads to
      improved endurance and functional ambulation, decreased supplemental oxygen use,
      and fewer hospitalizations 1 year after discharge for patients with COPD.

PMID- 11245758
TI  - Evaluation of clinical, electrophysiologic, and computed tomographic parameters
      in replanted hands.
AB  - OBJECTIVE: To compare clinical, electrophysiologic, and computed tomography (CT)
      imaging correlates of reinnervation in replanted limbs. DESIGN: Patients were
      assessed between 8 and 194 months after replantation of completely severed hands.
      SETTING: University hospital, departments for neurology and for plastic and
      reconstructive surgery. PARTICIPANTS: Thirteen patients, 10 with total and 3 with
      subtotal type V amputation, whose hands had been reattached. INTERVENTIONS:
      Clinical assessment of function of hand and finger muscles; electromyographic
      tests of sensory nerve action potentials (SNAPs) of median, ulnar, and radial
      nerves; and compound motor action potentials (CMAPs) of abductor pollicis brevis,
      first dorsal interosseus, and abductor digiti minimi muscles. CT assessment of
      motor unit action potentials. Measurements of both replanted and normal hands.
      MAIN OUTCOME MEASURES: Medical Research Council scale of force; sensory functions
      of anatomic areas of nerves; SNAP and CMAP amplitudes; CT area, mean absorption,
      standard deviation (SD) from mean absorption, and root mean square SD of
      absorption. RESULTS: Correlates of reinnervation were evidenced by all methods,
      except by surface recordings of SNAPs, which could not be elicited even in hands
      with good sensory function. CMAP amplitudes were the electrophysiologic parameter
      that correlated best with the clinical restoration. Of the CT measures, the cross
      sectional area was the most useful parameter for the detection of denervation,
      but no CT parameter was sufficiently sensitive to detect reinnervation. In cases
      with good functional recovery, CMAP amplitudes were superior to clinical rating
      in showing incomplete reinnervation. CONCLUSION: The combination of clinical and
      electrophysiologic methods supplied sufficient data for a reliable evaluation of
      reinnervation. Usually, CT parameters did not add useful information.

PMID- 11245759
TI  - Recovery from hip and knee arthroplasty: Patients' perspective on pain, function,
      quality of life, and well-being up to 6 months postoperatively.
AB  - OBJECTIVE: To provide a more detailed description from patients' perspectives
      than is yet available of recovery from hip and knee arthroplasty and to use this
      information to test 2 assumptions about recovery from these procedures: that
      recovery from knee arthroplasty, as assessed by patients, routinely reaches the
      level achieved by hip arthroplasty; and that fatigue is prolonged after major
      orthopedic surgery. DESIGN: A cohort study. SETTING: University teaching
      hospitals. PARTICIPANTS: Consecutive patients undergoing hip (n = 107) or knee (n
      = 53) arthroplasty. INTERVENTIONS: Unilateral hip or knee arthroplasty. MAIN
      OUTCOME MEASURES: Standardized self-rated measurements of pain, function, quality
      of life, and well-being from preoperatively to 6 months follow-up. RESULTS: Pain
      and function improved significantly less after knee arthroplasty than after hip
      arthroplasty, but the 2 procedures led to similar improvements in life
      evaluation, mood, and subjective health. Fatigue was only transiently increased.
      CONCLUSION: The findings were inconsistent with both assumptions. Nevertheless,
      despite poorer recovery in pain and function, patients receiving knee
      arthroplasty felt that life had improved as much as did patients with hip
      arthroplasty. Detailed information about how major joint arthroplasty in routine
      practice affects patients' lives can be used to advise patients and clinicians
      and can invalidate influential, but inaccurate, assumptions.

PMID- 11245760
TI  - Assessing traumatic brain injury outcome measures for long-term follow-up of
      community-based individuals.
AB  - OBJECTIVES: To determine which outcome measures are best and least suited for
      assessing long-term functional outcome of individuals with traumatic brain injury
      (TBI) in the community. DESIGN: Survey of participants in the community an
      average of 5 years after TBI. A battery of outcome measures was given. SETTING:
      Community in northern California after inpatient rehabilitation. PARTICIPANTS:
      Forty-eight adult individuals with prior moderate to severe TBI. All subjects had
      received inpatient rehabilitation 2 to 9 years previously and could be reached
      for telephone interview. MAIN OUTCOME MEASURES: The Community Integration
      Questionnaire, Neurobehavioral Functioning Inventory (NFI), Patient Competency
      Rating Scale (PCRS), Level of Cognitive Functioning Scale (LCFS), FIM instrument,
      Functional Assessment Measure (FIM+FAM), Supervision Rating Scale (SRS),
      Disability Rating Scale (DRS), Revised Craig Handicap Assessment and Reporting
      Technique (R-CHART), and Glasgow Outcome Scale (GOS). The number of maximal
      scores on each of the surveys was studied to determine which instruments
      continued to reveal deficits years after TBI. RESULTS: Most individuals obtained
      maximum scores, ie, functional independence, on these scales: LCFS, FIM motor
      subscale and total score, R-CHART physical independence subscale, FIM+FAM, GOS,
      and the SRS. Measures with the fewest maximum scores (<36%, measuring deficits
      still extant in the group) were the R-CHART cognition subscale and the NFI
      memory/attention and communication subscales, and employment subscales. Items,
      subscales, and total scores that showed good variability and correlated most
      highly and frequently with other scales also demonstrating good variability were
      the PCRS, the DRS and FIM+FAM employment items, the R-CHART cognition subscale,
      and the NFI motor, memory/attention, communication, and depression subscales (the
      R-CHART cognition subscale and NFI memory/attention subscale were highly
      correlated with the PCRS;.84,.83). CONCLUSIONS: Measures that appeared to
      contribute little to assessing functional status of a TBI sample years postinjury
      were the FIM, FIM+FAM, SRS, GOS, and LCFS. Measures that showed a range of
      deficits across participants were DRS employability, the NFI, PCRS, and the R
      CHART cognition subscale.

PMID- 11245761
TI  - Neurourologic findings in patients with traumatic thoracolumbar vertebra junction
      lesions.
AB  - OBJECTIVE: To investigate neurourologic involvement in injuries to the
      thoracolumbar vertebra junction with magnetic resonance imaging (MRI) and
      electrophysiologic and urodynamic measurements and to characterize the neurogenic
      mechanisms of voiding dysfunctions. DESIGN: Baseline comparisons among 3 anatomic
      groups before neural repair. SETTING: Tertiary care center. PATIENTS: Thirty-five
      T11 to L2 spinal cord injury patients consecutively admitted to a rehabilitation
      unit. Eight patients (Group 1) had above-conus lesions without denervation and
      polyphasic waves revealed in the anal sphincter electromyography; 13 patients
      (Group 2) had conal and/or above-conus lesions and anal sphincter
      electromyographic abnormalities; and 14 patients (Group 3) had below-conus
      lesions and anal sphincter electromyographic abnormalities. MAIN OUTCOME
      MEASURES: Comparison of features identified on pudendal nerve terminal motor
      latency, urethral pressure profiles, and multichannel voiding pressure-flow
      study. RESULTS: The pudendal nerve terminal motor latency in Group 3, showing a
      significantly higher abnormal ratio (100%; p =.011, Fisher's exact test),
      indicated that cauda equina lesions might be the cause. Urodynamic data from
      Group 3 showed a significant decrease in maximal urethral closure pressure (48 +/
      17cm H2O, p =.0022, analysis of variance [ANOVA], repeated measure) and an
      increase in bladder capacity (429 +/- 194mL, p =.037, ANOVA, repeated measure).
      There were no significant changes in the other groups. CONCLUSION: Neurourologic
      abnormalities are less predictable with injuries to thoracolumbar junction,
      except in patients with cauda equina lesions.

PMID- 11245762
TI  - New wheelie aid for wheelchairs: controlled trial of safety and efficacy.
AB  - OBJECTIVE: To test hypotheses that people learning to perform aided wheelies (AW)
      with a new self-deploying wheelie aid (WA) (1) are safer than those who use the
      conventional wheelie (CW), (2) are more successful at learning the skills, (3)
      learn more quickly, and (4) find such skills less difficult. DESIGN: Randomized,
      controlled study. SETTING: Wheelchair obstacle course. PARTICIPANTS: Forty-two
      subjects (12 wheelchair users, 30 able-bodied) randomly assigned to the CW (n =
      23) or AW (n = 19) groups. INTERVENTIONS: We performed static tests on a WA
      modified wheelchair occupied by a test dummy. We also attempted to teach each
      subject to perform a set of 14 wheelie-related skills. MAIN OUTCOME MEASURES:
      Visual analog scale (VAS) of safety, percentage of subjects able to learn the
      skills, the time required, and subjective difficulty scores (from 1 for "very
      easy" to 5 for "very difficult"). RESULTS: Up to 11.2 degrees of antitip-device
      stability was available without the WA extending beyond the rearmost aspect of
      the rear wheel in the resting position. For the CW and AW groups, the mean +/-
      standard deviation VAS safety scores were 43% +/- 27% and 98% +/- 2% (p <.0001),
      respectively; the overall success rates were 93% and 96% (p =.079), respectively;
      the mean times required to learn a skill (in 5-min increments) were 1.56 +/- 1.08
      minutes and.72 +/-.35 minutes (p =.002), respectively; and the mean difficulty
      scores were 2.94 +/-.38 and 2.23 +/-.34 (p <.0001), respectively. CONCLUSIONS:
      The new WA provides stability and wheelie-like function without interfering with
      maneuverability. Although both groups were equally successful, learning to
      perform AWs is safer, faster, and less difficult than learning CWs.

PMID- 11245763
TI  - Early rehabilitation effect for traumatic spinal cord injury.
AB  - OBJECTIVE: To determine the natural course of traumatic spinal cord injury (SCI)
      and the effect of early rehabilitation on it. DESIGN: A retrospective,
      multicenter study. SETTING: Sixteen Rosai hospitals and 1 medical school.
      PARTICIPANTS: One hundred twenty-three SCI patients (104 men, 19 women; mean age,
      48.8 +/- 17.7yr) enrolled. INTERVENTIONS: Dividing the subjects into an early
      rehabilitation group and a delayed group; differences were ensured by
      international classification of SCI. MAIN OUTCOME MEASURES: Using the American
      Spinal Injury Association (ASIA) classifications, the motor recovery rate (MRR)
      was defined as (ASIA motor score at discharge - ASIA motor score at
      admission)/(100 - ASIA motor score at admission). The regression lines for FIM
      instrument score and ASIA motor score were determined for 6 subgroups (early or
      delayed tetraplegia, central cord injury, paraplegia) by the MRR staging. The
      regression lines for physical or cognitive FIM score and ASIA motor score were
      also determined for 6 subgroups. RESULTS: Three stages were obtained: acute
      stage: 2 weeks postinjury; recovery stage: 2 weeks to 6 months postinjury; and
      chronic stage: more than 6 months postinjury. Regression lines showed that
      rehabilitation improved physical functional independence for ASIA motor score,
      especially in the early rehabilitation subgroups. There was no correlation
      between cognitive FIM score and ASIA motor score in 6 subgroups. CONCLUSION:
      Early SCI rehabilitation contributes to good physical activities of daily living
      for motor function.

PMID- 11245764
TI  - Intra- and intertester reliability and criterion validity of the parallelogram
      and universal goniometers for measuring maximum active knee flexion and extension
      of patients with knee restrictions.
AB  - OBJECTIVE: To examine the intra- and intertester reliability of the universal
      goniometer (UG) and parallelogram goniometer (PG), and to assess the criterion
      validity of the same instruments on subjects with knee restrictions. DESIGN:
      Reliability and validation study. SETTING: Radiology department at university
      hospital. PARTICIPANTS: Sixty subjects (34 men, 26 women; mean age, 52yr) with
      various knee restrictions. INTERVENTIONS: Sixteen goniometric measurements were
      collected per patient by 2 physical therapists. Subjects were evaluated in knee
      flexion and knee extension positions. To serve as a gold standard, radiographs
      were taken in both positions. MAIN OUTCOME MEASURES: Active knee flexion and knee
      extension on 2 goniometers, radiographs. Maximum active range of motion (AROM).
      RESULTS: The UG intratester reliability (intraclass correlation coefficients
      [ICCs]) was .997 in flexion and .972 to .985 in extension. The results were also
      high with the PG (ICC =.996,.953-.955) for flexion and extension, respectively.
      The intertester reliability was high for flexion (ICC =.977-.982) and for
      extension (ICC =.893-.926) when using the UG. For the PG, ICC results ranged from
      .959 to .970 for flexion and from .856 to .898 for extension. Criterion validity
      (r) varied from .975 to .987 for flexion and from .390 to .442 for extension with
      the UG, and from .976 to .985 for flexion and .423 to .514 for extension with the
      PG. CONCLUSION: Intra- and intertester reliability were high for both
      goniometers. The results for the criterion validity varied. Our study also
      revealed that it is preferable to use goniometry rather than visual estimations
      when measuring AROM. It is recommended that the same therapist take all the
      measurements when assessing AROM for UG and PG goniometric measurements on
      patients with knee restrictions.

PMID- 11245765
TI  - Effects of upper limb unilateral isometric efforts on postural stabilization in
      subjects with hemiparesis.
AB  - OBJECTIVE: To characterize postural stabilization during a progressive unilateral
      isometric abduction of the upper limb in a seated position in healthy subjects
      and subjects with hemiparesis. DESIGN: Convenience sample. SETTING: University
      secondary care rehabilitation center. PATIENTS: Twelve patients with hemiparesis
      and 12 subjects without neurologic disorder. INTERVENTIONS: Subjects were seated
      on a forceplate, with forearms fixed in cuffs mounted on a force transducer. Two
      trials per side of isometric abduction of arm were conducted. The orthogonal
      force and torque exerted was measured for each arm. MAIN OUTCOME MEASURES: Forces
      at the upper limbs and at the seat, global motor performance, spasticity of upper
      limb, grip force, and dexterity. RESULTS: Results of analyses of variance showed
      differences in the magnitude of the contralateral limb forces generated by
      subjects with hemiparesis and healthy subjects (p <.05). Normalized contralateral
      forces in the nonparetic upper limb associated with paretic isometric efforts
      were higher than those associated with nonparetic efforts and higher than those
      associated with efforts in healthy subjects. CONCLUSION: These results suggest
      that postural stabilization during isometric efforts is impaired in subjects with
      hemiparesis.

PMID- 11245766
TI  - Reflex sympathetic dystrophy with hidradenitis suppurativa exacerbation: a case
      report.
AB  - Reflex sympathetic dystrophy (RSD) or complex regional pain syndrome type 1, is
      characterized by spontaneous pain or allodynia and hyperalgesia disproportionate
      to the inciting event, multiperipheral nerve involvement, edema, vasomotor or
      sudomotor change, and possible loss of function. It has been described in
      relation to various insults, including a number of infectious and inflammatory
      conditions. We report a case of a patient who developed RSD 1 week after an
      exacerbation of hidradenitis suppurativa, a rare chronic inflammatory disease of
      apocrine sweat glands. The patient responded well to a combination of range-of
      motion exercises, thermal modalities, and oral steroids. Hidradenitis suppurativa
      should be considered when searching for an etiology of new onset RSD.

PMID- 11245767
TI  - Bilateral, simultaneous, spontaneous rupture of quadriceps tendons without trauma
      in an obese patient: a case report.
AB  - This is a single case report of bilateral, simultaneous, spontaneous rupture of
      the quadriceps tendon caused by obesity without trauma. The patient was a 52-year
      old, 350-pound, morbidly obese man with a sedentary life style whose quadriceps
      tendons ruptured while he was descending a staircase. He presented with a large
      deficit superior to the patella and an inability to straighten his knees. After
      surgery, his knees were immobilized in extension for 6 weeks, followed by gradual
      weight bearing and gait training with braces. He was weaned off the braces as he
      increased the range of motion and strength in his knees. The rehabilitation
      process was protracted, and he returned to full-time work 6 months postinjury.
      Physiatrists should be familiar with the diagnosis, treatment, and rehabilitation
      of this rare condition.

PMID- 11245768
TI  - The validity and reliability of the GAITRite system's measurements: A preliminary
      evaluation.
AB  - OBJECTIVE: To compare the concurrent validity and reliability of the GAITRite
      computerized gait analysis system with validated paper-and-pencil and video-based
      methods. DESIGN: Within-groups, repeated-measures design. SETTING: Research
      laboratory in a physical therapy education program. PARTICIPANT: One healthy
      woman, age 27 years. INTERVENTIONS: A subject walked across the walkway of the
      GAITRite system at various walking rates and degrees of step symmetry for 2 of
      the 3 analyses. Paper placed over the walkway enabled concurrent paper-and-pencil
      analysis. The subject was concurrently videotaped from the side. For the other
      analysis, a stride simulator with known step and stride lengths was applied to
      the walkway to simulate 2 steps and 1 stride. MAIN OUTCOME MEASURES: Cadence,
      walking speed, right and left step and stride lengths, and right and left step
      times. RESULTS: Excellent paper-and-pencil and GAITRite correlations (intraclass
      correlation coefficient [ICC] > 95) for spatial measures and excellent video
      based and GAITRite correlations (ICC > 93) for temporal measures were found.
      GAITRite measures of step lengths and times were reliable in both walkway center
      and left-of-center measurements. CONCLUSIONS: Based on this data, GAITRite is a
      valid and reliable tool for measuring selected spatial and temporal parameters of
      gait.

PMID- 11245769
TI  - Postinjection vastus lateralis atrophy.

PMID- 11245772
TI  - Genetic renal tubular disorders of renal ion channels and transporters.
AB  - This perspective on genetic renal tubular transport disorders selectively reviews
      the pathophysiology of renal apical Na(+) transport systems. These transporters
      play an essential role in the control of extracellular fluid volume and blood
      pressure. Significant advancements in the understanding of the role of these
      genes in Mendelian forms of extracellular volume homeostatic disorders have been
      achieved in the recent years. Of even greater importance will be the ongoing
      definition of the various factors that regulate the expression and activity of
      the Na(+) transport systems. These regulatory pathways, and the responses to
      environmental factors such as dietary salt, stress, and so on, may determine the
      appearance, severity and complexity of the clinical phenotypes that result from
      genetic disorders of the renal apical Na(+) transporters.

PMID- 11245773
TI  - Biochemical and genetic advances in distal renal tubular acidosis.
AB  - Distal renal tubular acidosis is a constellation of syndromes arising from
      different derangements of tubular acid transport. Recent advances in the biology
      of urinary acidification have allowed us to discern various molecular mechanisms
      responsible for these syndromes. This article relates clinical disorders of
      distal acidification to the underlying defective mechanisms responsible for them.
      A clinical classification of these disorders is presented which integrates each
      disorder with the prevailing serum potassium concentration. That distal renal
      tubular acidosis can be associated with low, normal, or high serum potassium
      concentration is now explainable by identifying the specific defect in transport
      causing each syndrome.

PMID- 11245774
TI  - The genetics and physiology of polycystic kidney disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a major, inherited
      disorder that is characterized by the growth of large, fluid-filled cysts from
      the tubules and collecting ducts of affected kidneys, and by a number of
      extrarenal manifestations including liver and pancreatic cysts, hypertension,
      heart valve defects, and cerebral and aortic aneurysms. Mutations in either of 2
      different genes (PKD1 or PKD2) give rise to ADPKD. Most mutations identified in
      affected families appear to inactivate the PKD genes, and accumulating evidence
      suggests that a 2-hit mechanism, in which the normal PKD1 or PKD2 allele is also
      mutated, may be required for cyst growth. The protein products of the PKD genes
      (polycystin-1 and polycystin-2) are thought to function together as part of a
      multiprotein membrane-spanning complex involved in cell-cell or cell-matrix
      interactions. Polycystin-1 and polycystin-2 can initiate signal transduction,
      leading to the activation of a number of downstream effectors, including
      heterotrimeric G-proteins, protein kinase C, mitogen-activated protein kinases,
      beta-catenin, and the AP-1 transcription factor. In addition, polycystin-2 may
      function in mediating calcium flux. The pathogenesis of cyst formation is
      currently thought to involve increased cell proliferation, fluid accumulation,
      and basement membrane remodeling. It now appears that cyclic adenosine
      monophosphate (cAMP) metabolism is a central component of cyst formation,
      stimulating apical chloride secretion and driving the accumulation of cyst fluid.
      Recent evidence has shown that ADPKD cells also have an altered responsiveness to
      cyclic AMP. In contrast to normal kidney cells whose cell proliferation is
      inhibited by cyclic AMP, ADPKD cells are stimulated to proliferate. Thus, it is
      likely that an alteration in polycystin function transforms the normal cellular
      phenotype to one that responds to elevated cyclic AMP by an increased rate of
      cell proliferation and that the enlarging cyst expands by an increased rate of
      cyclic AMP-driven fluid secretion. Cyclic AMP and growth factors, including
      epidermal growth factor, have complementary effects to accelerate the enlargement
      of ADPKD cysts, and thereby to contribute to the progression of the disease. This
      knowledge should facilitate the discovery of inhibitors of signal transduction
      cascades that can be used in the treatment of ADPKD.

PMID- 11245775
TI  - In memory of a legendary athlete: measured success in diabetic nephropathy.
AB  - Historically diabetic nephropathy has been a devastating complication of both
      type I and type II diabetes. The past 2 decades have seen enormous conceptual
      advances in understanding the pathogenesis of diabetic nephropathy. The genetic
      determinants of diabetic renal disease have also been elucidated as well as
      biochemical events and cytokine interactions. Most importantly, key clinical
      trials have identified therapeutic interventions which can slow or halt the
      progression of diabetic nephropathy, specifically the therapeutic use of
      angiotensin-converting enzyme inhibition and intensive blood sugar control.
      Multiple treatment modalities for patients once they reach end-stage renal
      disease are also available and great strides have been improving outcomes in
      these areas as well.

PMID- 11245776
TI  - Urinary tract obstruction.
AB  - Angiotensin II plays a pivotal role in the progression of renal diseases,
      including obstructive nephropathy. Increasing levels of angiotensin II in
      obstructive nephropathy upregulate the expression of several factors:
      transforming growth factor-beta1 (TGF-beta1), tumor necrosis factor-alpha (TNF
      alpha), platelet-derived growth factor (PDGF), insulin-like growth factor (IGF
      1), osteopontin, vascular cell adhesion molecule-1 (VCAM-1), nuclear factor
      kappaB (NF-kappaB), monocyte chemoattractant peptide-1 (MCP-1), intercellular
      adhesion molecule-1 (ICAM-1), and CD14 among others. Local production of TGF
      beta, by intrinsic renal cells or by macrophages invading the kidney, is a key
      mediator of renal fibrosis. Activation of TGF-beta stimulates endothelin
      production. Endothelin, in turn, is a potent stimulus for fibrogenesis. Oxidative
      stress, fueled in part by angiotensin II, upregulates the expression of adhesion
      molecules, chemoattractant compounds and cytokines. Sustained obstructive
      nephropathy leads to apoptosis of tubular epithelial cells. Several factors and
      genes involved in apoptosis have been described. Nuclear factor kappa-B is
      involved in the transcriptional regulation of genes present in several organs,
      including the kidney. NF-kappaB is activated in the setting of ureteral
      obstruction. Administration of angiotensin-converting enzyme (ACE) inhibitors
      decreased significantly the activation of NF-kappaB in the obstructed kidney.
      Studies in neonatal rats indicate that chronic ureteral obstruction decreases the
      expression of epidermal growth factor (EGF). Replacement of this factor decreased
      apoptosis and reduced the expression of vimentin, clusterin, and TGF-beta. The
      administration of IGF-1 also lessened the tubular and interstitial pathology in
      the setting of ureteral obstruction. A spectrum of urinary tract malformations
      have been described. The utility of certain markers such as fetal serum beta(2)
      microglobulin as a predictor of postnatal renal function in bilateral uropathies
      has been described. A number of pharmacologic interventions that ameliorate the
      increased expansion of the interstitial volume, decrease the expression of TGF
      beta, and down-regulate the production of extracellular matrix and the
      infiltration of the interstitium by macrophages have been described. Drugs used
      include ACE inhibitors, administration of arginine, administration of osteogenic
      protein-1, Pirferidone, and so on. It is likely that in the next decade advances
      in genetic manipulations and new drug therapies may forestall the development of
      fibrosis in the setting of urinary tract obstruction.

PMID- 11245777
TI  - Hypertension in chronic renal failure and ESRD: prevalence, pathophysiology, and
      outcomes.
AB  - Hypertension and cardiovascular disease were detected to be major problems in end
      stage renal disease patients soon after the application of chronic dialysis to
      treat uremia. Nearly 40 years later, and despite awesome technological and
      pharmacological advances, cardiovascular diseases remain the number one cause of
      death in all categories of renal patients, ie, chronic renal insufficiency, end
      stage renal disease on dialysis and the renal transplant recipient. This is quite
      likely related to the massive clinical burden of cardiovascular risk factors:
      hypertension, cardiac fibrosis and hypertrophy, abnormal lipid profiles, smoking,
      dietary factors, and enhanced sympathetic activity. For example, left ventricular
      hypertrophy and abnormal echocardiograms are present in up to 75% to 80% of
      incident dialysis patients related to the interactions of these cardiovascular
      risks. It is important to understand how hypertension and the other
      cardiovascular disease risk factors interact in these patients. Based on the
      latest national data from the USRDS, the prevalence of underlying cardiac disease
      is increasing during the period of chronic renal failure. A proper understanding
      of the pathophysiology and prevalence of hypertension and its consequences in
      renal patients may lead to more rational therapies and clinical trials. At this
      time, the nephrologists are dealing with an epidemic of cardiovascular diseases
      in their patients.

PMID- 11245778
TI  - Pathogenesis and management of sodium and water retention in cardiac failure and
      cirrhosis.
AB  - The kidneys play the crucial role in the maintenance of the body fluid volume
      homeostasis. Several hypotheses have been introduced to explain sodium and water
      retention leading to edematous states in such pathologic conditions as congestive
      heart failure (CHF) and cirrhosis. We have suggested a unifying arterial
      underfilling hypothesis, explaining the development of edema in these conditions.
      Arterial underfilling, caused by decreased cardiac output or peripheral arterial
      vasodilation, leads to activation of the sympathetic nervous system, renin
      angiotensin-aldosterone system, and nonosmotic vasopressin release. This review
      discusses the pathophysiologic mechanisms resulting in renal sodium and water
      retention, impaired mineralocorticoid escape, and resistance to atrial
      natriuretic peptide in patients with CHF and cirrhosis. Furthermore, the basis of
      current therapies in these disorders is discussed, including beta-blockers,
      angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers,
      aldosterone antagonists, and diuretics in CHF and cirrhosis, as well as new
      approaches to treatment of water retention with vasopressin V(2) receptor
      antagonists.

PMID- 11245779
TI  - The kidney and hypertension in pregnancy: twenty exciting years.
AB  - Before 1980 research on the kidney and hypertension during pregnancy was
      neglected, although these diseases, especially hypertension, are major causes of
      morbidity to mother and child. The past 20 years, however, has witnessed a
      striking reversal of this neglect. This review focuses on recent progress in
      renal physiology, kidney disease, and hypertension as relates to pregnancy. Why
      do renal hemodynamics increase markedly in pregnancy? Studies have suggested
      roles for nitric oxide synthase, prostaglandins, endothelin and relaxin. This
      area of research is exciting, as unraveling why glomerular filtration rate and
      renal plasma flow increase in pregnancy may eventually help all patients with
      acute and chronic renal function loss. Concerning other advances: Micropuncture
      studies in rats, and the interpretation of fractional dextran clearances in
      humans show that the hyperfiltration that occurs during normal gestation is not
      associated with increased glomerular capillary pressure. Finally, description of
      changes in osmoregulation and in the metabolic disposal of arginine vasopressin
      in human pregnancy led to identification and appropriate treatment of a new group
      of disorders termed "transient diabetes insipidus of pregnancy." Chronic renal
      disease of any severity once led to proscription or interrupting of pregnancy.
      Clinical-pathological correlation studies and long-term follow-up of the mothers
      have revealed that most of these gestations succeed with little risk of worsening
      the natural history of the kidney disorder. This is also true in allograft
      recipients, and we now have guidelines to counsel both groups of patients.
      Progress relating to hypertension in pregnancy has been in 2 broad areas;
      systematic attempts to accurately define and differentiate the various disorders
      and population studies to predict, prevent, and improve the management of
      preeclampsia. There has also been considerable progress in unraveling the
      pathophysiology and identifying the cause of preeclampsia.

PMID- 11245780
TI  - Erythropoietin and anemia.
AB  - Recombinant human erythropoietin (rHuEPO) has revolutionized the treatment of
      anemia of chronic renal failure. RHuEPO has been shown to increase survival,
      decrease hospitalizations, improve brain and cognitive function, and improve
      quality of life for renal patients. Much has been learned about the normal and
      pathologic physiology of anemia because rHuEPO has become available to
      investigators, and this has been widely applied. Additional work is needed in
      better defining the sites of production of endogenous EPO as well as the nature
      and control of the oxygen sensor(s) in the kidney. Remaining clinical issues
      related to this remarkable compound include predicting and overcoming resistance;
      avoiding iron deficiency; determining the appropriate target hemoglobin;
      increasing the use strategies such as subcutaneous administration to increase
      efficiency; and devising a more rational payment scheme.

PMID- 11245781
TI  - Dialysis.
AB  - Willem Kolff designed his "kunstmatige nier" in the early 1940s using spare parts
      obtained from the Wehrmacht; with it, he treated 14 patients with acute renal
      failure. Although there has been a tremendous improvement in the design and
      construction of dialysis machines, the basic concepts are unchanged. In this
      review we show that dialysis dose and adequacy can now be predicted using simple
      clinical methodology. The second part of the article discusses the accumulation
      or excess removal of important biologically active substances which can result in
      hitherto unseen clinical syndromes and even pose a threat to life.

PMID- 11245782
TI  - Renal transplantation.
AB  - Renal Transplantation has progressed from an experiment in surgery, nephrology,
      and immunology to the preferred means of renal replacement therapy for patients
      with end-stage renal disease. Patient and graft survival rates are spectacular in
      the short run and improving steadily in the long. The current state of the art
      reflects deepened understanding of the alloimmune response and the T lymphocyte
      activation cascade in part driving the discovery of ever more potent
      immunosuppressive agents. Important issues remain such as chronic allograft
      dysfunction, the organ shortage, and tolerance induction. In this review, we will
      look at the history, the expanding treatment options based on better
      understanding of the immunobiology of alloantigen response, and the persistent
      challenges awaiting.

PMID- 11245783
TI  - Evidence for a quinone binding site close to the interface between NUOD and NUOB
      subunits of Complex I.
AB  - Piericidin, rotenone and pyridaben are specific inhibitors of the NADH-ubiquinone
      oxidoreductase (Complex I) that bind to its ubiquinone binding site(s). Using
      site directed mutagenesis, we demonstrate that residues G409, D412, R413 and V407
      of the C-terminus of Complex I NUOD subunit are directly involved in the binding
      of these inhibitors. We propose that the corresponding inhibitor/quinone binding
      site would be located close to NUOD-NUOB interface.

PMID- 11245784
TI  - Fungal respiration: a fusion of standard and alternative components.
AB  - In animals, electron transfer from NADH to molecular oxygen proceeds via large
      respiratory complexes in a linear respiratory chain. In contrast, most fungi
      utilise branched respiratory chains. These consist of alternative NADH
      dehydrogenases, which catalyse rotenone insensitive oxidation of matrix NADH or
      enable cytoplasmic NADH to be used directly. Many also contain an alternative
      oxidase that probably accepts electrons directly from ubiquinol. A few fungi lack
      Complex I. Although the alternative components are non-energy conserving, their
      organisation within the fungal electron transfer chain ensures that the transfer
      of electrons from NADH to molecular oxygen is generally coupled to proton
      translocation through at least one site. The alternative oxidase enables
      respiration to continue in the presence of inhibitors for ubiquinol:cytochrome c
      oxidoreductase and cytochrome c oxidase. This may be particularly important for
      fungal pathogens, since host defence mechanisms often involve nitric oxide,
      which, whilst being a potent inhibitor of cytochrome c oxidase, has no inhibitory
      effect on alternative oxidase. Alternative NADH dehydrogenases may avoid the
      active oxygen production associated with Complex I. The expression and activity
      regulation of alternative components responds to factors ranging from oxidative
      stress to the stage of fungal development.

PMID- 11245785
TI  - Generation and propagation of radical reactions on proteins.
AB  - The oxidation of proteins by free radicals is thought to play a major role in
      many oxidative processes within cells and is implicated in a number of human
      diseases as well as ageing. This review summarises information on the formation
      of radicals on peptides and proteins and how radical damage may be propagated and
      transferred within protein structures. The emphasis of this article is primarily
      on the deleterious actions of radicals generated on proteins, and their
      mechanisms of action, rather than on enzymatic systems where radicals are
      deliberately formed as transient intermediates. The final section of this review
      examines the control of protein oxidation and how such damage might be limited by
      antioxidants.

PMID- 11245786
TI  - Stoichiometry of subunit e in rat liver mitochondrial H(+)-ATP synthase and
      membrane topology of its putative Ca(2+)-dependent regulatory region.
AB  - Previous studies have revealed that residues 34-65 of subunit e of mitochondrial
      H(+)-ATP synthase are homologous with the Ca(2+)-dependent tropomysin-binding
      region for troponin T and have suggested that subunit e could be involved in the
      Ca(2+)-dependent regulation of H(+)-ATP synthase activity. In this study, we
      determined the content of subunit e in H(+)-ATP synthase purified from rat liver
      mitochondria, and we also investigated the membrane topology of a putative Ca(2+)
      dependent regulatory region of subunit e using an antibody against peptide
      corresponding to residues 34-65 of subunit e. Quantitative immunoblot analysis of
      subunit e in the purified H(+)-ATP synthase revealed that 1 mol of H(+)-ATP
      synthase contained 2 mol of subunit e. The ATPase activity of mitoplasts, in
      which the C-side of F(0) is present on the outer surface of the inner membrane,
      was significantly stimulated by the addition of the antibody, while the ATPase
      activity of submitochondrial particles and purified H(+)-ATP synthase was not
      stimulated. The antibody bound to mitoplasts but not to submitochondrial
      particles. These results suggest that the putative Ca(2+)-dependent regulatory
      region of subunit e is exposed on the surface of the C-side of F(0) and that
      subunit e is involved in the regulation of mitochondrial H(+)-ATP synthase
      activity probably via its putative Ca(2+)-dependent regulatory region.

PMID- 11245787
TI  - Temperature-induced decoupling of phycobilisomes from reaction centers.
AB  - Temperature-induced decoupling of phycobilisomes (PBSs) from the reaction centers
      in the PBS-thylakoid membrane complexes was observed at 0 degrees C. The
      fluorescence yields of photosystem (PS) I and PSII decreased and that of PBSs
      increased with selective excitation of PBSs at 0 degrees C, while the yield of
      PBSs decreased and those of the two photosystems increased with selective
      excitation of chlorophyll a at room temperature (RT). It indicated that the
      decoupling of PBSs from the two photosystems led to changes of energy transfer
      efficiencies, which can be explained by partial detachment of PBSs from thylakoid
      membrane. The temperature-dependent processes were reversible, i.e. with
      temperature going up to RT, the complexes could restore to the functionally
      coupled state with a time constant about 30 s. Based on these results, it could
      be deduced that PBSs should be in parallel connection with the two photosystems.

PMID- 11245788
TI  - Modification of inhibitor binding sites in the cytochrome bf complex by directed
      mutagenesis of cytochrome b(6) in Synechococcus sp. PCC 7002.
AB  - The cytochrome bf complex, which links electron transfer from photosystem II to
      photosystem I in oxygenic photosynthesis, has not been amenable to site-directed
      mutagenesis in cyanobacteria. Using the cyanobacterium Synechococcus sp. PCC
      7002, we have successfully modified the cytochrome b(6) subunit of the cytochrome
      bf complex. Single amino acid substitutions in cytochrome b(6) at the positions
      D148, A154, and S159 revealed altered binding of the quinol-oxidation inhibitors
      2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB), myxothiazol, and
      stigmatellin. Cytochrome bf and mitochondrial-type cytochrome bc(1) complexes are
      closely related in structure and function but exhibit quite different inhibitor
      specificities. Cytochrome bf complexes are insensitive to myxothiazol and
      sensitive to DBMIB, whereas cytochrome bc(1) complexes are sensitive to
      myxothiazol and relatively insensitive to DBMIB. Measurements of flash-induced
      and steady-state electron transfer rates through the cytochrome bf complex
      revealed increased resistance to DBMIB in the mutants A154G and S159A, increased
      resistance to stigmatellin in A154G, and created sensitivity to myxothiazol in
      the mutant D148G. Therefore these mutations made the cytochrome bf complex more
      like the cytochrome bc(1) complex. This work demonstrates that cyanobacteria can
      be used as effective models to investigate structure-function relationships in
      the cytochrome bf complex.

PMID- 11245790
TI  - The oxidation state of the photosystem II manganese cluster influences the
      structure of manganese stabilizing protein.
AB  - Exposure of photosystem II membranes to trypsin that has been treated to inhibit
      chymotrypsin activity produces limited hydrolysis of manganese stabilizing
      protein. Exposure to chymotrypsin under the same conditions yields substantial
      digestion of the protein. Further probing of the unusual insensitivity of
      manganese stabilizing protein to trypsin hydrolysis reveals that increasing the
      temperature from 4 to 25 degrees C will cause some acceleration in the rate of
      proteolysis. However, addition of low (100 microM) concentrations of NH2OH, that
      are sufficient to reduce, but not destroy, the photosystem II Mn cluster, causes
      a change in PS II-bound manganese stabilizing protein that causes it to be
      rapidly digested by trypsin. Immunoblot analyses with polyclonal antibodies
      directed against the N-terminus of the protein, or against the entire sequence
      show that trypsin cleavage produces two distinct peptide fragments estimated to
      be in the 17-20 kDa range, consistent with proposals that there are 2 mol of the
      protein/mol photosystem II. The correlation of trypsin sensitivity with Mn redox
      state(s) in photosystem II suggest that manganese stabilizing protein may
      interact either directly with Mn, or alternatively, that the polypeptide is bound
      to another protein of the photosystem II reaction center that is intimately
      involved in binding and redox activity of Mn.

PMID- 11245789
TI  - The rapid mode of calcium uptake into heart mitochondria (RaM): comparison to RaM
      in liver mitochondria.
AB  - A mechanism of Ca(2+) uptake, capable of sequestering significant amounts of
      Ca(2+) from cytosolic Ca(2+) pulses, has previously been identified in liver
      mitochondria. This mechanism, the Rapid Mode of Ca(2+) uptake (RaM), was shown to
      sequester Ca(2+) very rapidly at the beginning of each pulse in a sequence
      [Sparagna et al. (1995) J. Biol. Chem. 270, 27510-27515]. The existence and
      properties of RaM in heart mitochondria, however, are unknown and are the basis
      for this study. We show that RaM functions in heart mitochondria with some of the
      characteristics of RaM in liver, but its activation and inhibition are quite
      different. It is feasible that these differences represent different
      physiological adaptations in these two tissues. In both tissues, RaM is highly
      conductive at the beginning of a Ca(2+) pulse, but is inhibited by the rising
      [Ca(2+)] of the pulse itself. In heart mitochondria, the time required at low
      [Ca(2+)] to reestablish high Ca(2+) conductivity via RaM i.e. the 'resetting
      time' of RaM is much longer than in liver. RaM in liver mitochondria is strongly
      activated by spermine, activated by ATP or GTP and unaffected by ADP and AMP. In
      heart, RaM is activated much less strongly by spermine and unaffected by ATP or
      GTP. RaM in heart is strongly inhibited by AMP and has a biphasic response to
      ADP; it is activated at low concentrations and inhibited at high concentrations.
      Finally, an hypothesis consistent with the data and characteristics of liver and
      heart is presented to explain how RaM may function to control the rate of
      oxidative phosphorylation in each tissue. Under this hypothesis, RaM functions to
      create a brief, high free Ca(2+) concentration inside mitochondria which may
      activate intramitochondrial metabolic reactions with relatively small amounts of
      Ca(2+) uptake. This hypothesis is consistent with the view that
      intramitochondrial [Ca(2+)] may be used to control the rate of ADP
      phosphorylation in such a way as to minimize the probability of activating the
      Ca(2+)-induced mitochondrial membrane permeability transition (MPT).

PMID- 11245791
TI  - Chloroplastic ascorbate peroxidase is the primary target of methylviologen
      induced photooxidative stress in spinach leaves: its relevance to
      monodehydroascorbate radical detected with in vivo ESR.
AB  - Methylviologen (MV) induces oxidative damages in leaves. In order to understand
      its mechanism we studied initial biochemical events under light in MV-fed spinach
      leaves. When isolated chloroplasts were illuminated in the presence of MV, both
      stromal and thylakoid-bound ascorbate peroxidases (APX) were inactivated rapidly
      at the same rates, and their inactivation was retarded by ascorbate (AsA) at
      higher concentrations. Since MV accelerates the photoproduction of O2- in
      Photosystem (PS) I and simultaneously inhibits the photoreduction of
      monodehydroascorbate (MDA) to AsA, the inactivation of APX was attributed to the
      loss of AsA and accumulation of H2O2 in the stroma. Following APX, superoxide
      dismutase and NADP(+)-glyceraldehyde 3-phosphate dehydrogenase, both of which are
      vulnerable to H2O2, were inactivated by MV plus light. Dehydroascorbate
      reductase, monodehydroascorbate reductase, PS II, PS I and ferredoxin-NADP(+)
      reductase were far less sensitive to the treatment. In the treated leaves,
      cytosolic APX and guaiacol-specific peroxidase were also inactivated, but slower
      than chloroplastic APXs were. Catalase was not inactivated. Thus the MV-induced
      photooxidative damages of leaves are initiated with the inactivation of
      chloroplastic APXs and develop via the inactivation of other H2O2-sensitive
      targets. The decay half-life of the MDA signal after a short illumination in the
      leaves, as determined by in vivo electron spin resonance spectrometry (ESR), was
      prolonged when the H2O2-scavenging capacity of the leaf cells was abolished by
      the inactivation of chloroplastic and cytosolic APXs. The measurement of MDA in
      leaves by ESR, therefore, allows to estimate in vivo cellular capacity to
      scavenge the photoproduced H2O2.

PMID- 11245792
TI  - Photoreducible high spin iron electron paramagnetic resonance signals in dark
      adapted Photosystem II: are they oxidised non-haem iron formed from interaction
      of oxygen with PSII electron acceptors?
AB  - An electron paramagnetic resonance (EPR) signal near g=6 in Photosystem II (PSII)
      membranes has been assigned to a high spin form of cytochrome (Cyt) b(559) (R.
      Fiege, U. Schreiber, G. Renger, W. Lubitz, V.A. Shuvalov, FEBS Lett. 377 (1995)
      325-329). Here we have further investigated the origin of this signal. A slow
      formation of the signal during storage in the dark is observed in oxygen-evolving
      PSII membranes, which correlate with the oxidation of Fe(2+) by plastosemiquinone
      or oxygen. Removal of oxygen inhibits formation of the high spin iron signal. The
      g=6 EPR signal is photoreduced at cryogenic temperatures and is restored slowly
      by subsequent dark storage at 77 K. The amplitude of the photoreduced signal
      increases as the pH is lowered, which shows that the origin is not the hydroxyl
      ligated Cyt b(559) species proposed previously. Different cryoprotectants also
      influence the amplitude and lineshape of the high spin iron signal in a manner
      suggesting that smaller cryoprotectants can penetrate the iron environment. A
      correlation between the high spin iron and g=1.6 EPR signal assigned to an
      interaction involving the semiquinones of Qa and Qb is shown. It is concluded
      that the appearance of the high spin iron signal in oxygen-evolving PSII
      membranes involves reduced PSII electron acceptors and oxygen and suggests that
      the signal is from the non-haem iron of PSII.

PMID- 11245793
TI  - Two functionally distinct manganese clusters formed by introducing a mutation in
      the carboxyl terminus of a photosystem II reaction center polypeptide, D1, of the
      green alga Chlamydomonas reinhardtii.
AB  - To study the function of the carboxyl-terminal domain of a photosystem II (PSII)
      reaction center polypeptide, D1, chloroplast mutants of the green alga
      Chlamydomonas reinhardtii have been generated in which Leu-343 and Ala-344 have
      been simultaneously or individually replaced by Phe and Ser, respectively. The
      mutants carrying these replacements individually, L343F and A344S, showed a wild
      type phenotype. In contrast, the double mutant, L343FA344S, evolved O2 at only 20
      30% of the wild-type rate and was unable to grow photosynthetically. In this
      mutant, PSII accumulated to 60% of the wild-type level, indicating that the O2
      evolving activity per PSII was reduced to approximately half that of the wild
      type. However, the amount of Mn atom detected in the thylakoids suggested that a
      normal amount of Mn cluster was assembled. An investigation of the kinetics of
      flash-induced fluorescence yield decay revealed that the electron transfer from
      Q(-)(A) to Q(B) was not affected. When a back electron transfer from Q(-)(A) to a
      donor component was measured in the presence of 3-(3,4-dichlorophenol)-1,1
      dimethylurea, a significantly slower component of the Q(-)(A) oxidation was
      detected in addition to the normal component that corresponds to the back
      electron transfer from the Q(-)(A) to the S(2)-state of the Mn cluster.
      Thermoluminescence measurements revealed that L343FA344S cells contained two
      functionally distinct Mn clusters. One was equivalent to that of the wild-type,
      while the other was incapable of water oxidation and was able to advance the
      transition from the S(1)-state to the S(2)-state. These results suggested that a
      fraction of the Mn cluster had been impaired by the L343FA344S mutation, leading
      to decreased O2 evolution. We concluded that the structure of the C-terminus of
      D1 is critical for the formation of the Mn cluster that is capable of water
      oxidation, in particular, transition to higher S-states.

PMID- 11245794
TI  - Long-lived charge-separated states in bacterial reaction centers isolated from
      Rhodobacter sphaeroides.
AB  - We studied the accumulation of long-lived charge-separated states in reaction
      centers isolated from Rhodobacter sphaeroides, using continuous illumination, or
      trains of single-turnover flashes. We found that under both conditions a long
      lived state was produced with a quantum yield of about 1%. This long-lived
      species resembles the normal P(+)Q(-) state in all respects, but has a lifetime
      of several minutes. Under continuous illumination the long-lived state can be
      accumulated, leading to close to full conversion of the reaction centers into
      this state. The lifetime of this accumulated state varies from a few minutes up
      to more than 20 min, and depends on the illumination history. Surprisingly, the
      lifetime and quantum yield do not depend on the presence of the secondary
      quinone, Q(B). Under oxygen-free conditions the accumulation was reversible, no
      changes in the normal recombination times were observed due to the intense
      illumination. The long-lived state is responsible for most of the dark adaptation
      and hysteresis effects observed in room temperature experiments. A simple method
      for quinone extraction and reconstitution was developed.

PMID- 11245795
TI  - Evaluation of the hydrogen bonding interactions and their effects on the
      oxidation-reduction potentials for the riboflavin complex of the Desulfovibrio
      vulgaris flavodoxin.
AB  - The oxidation-reduction potentials for the riboflavin complex of the
      Desulfovibrio vulgaris flavodoxin are substantially different from those of the
      flavin mononucleotide (FMN) containing native protein, with the midpoint
      potential for the semiquinone-hydroquinone couple for the riboflavin complex
      being 180 mV less negative. This increase has been attributed to the absence in
      the riboflavin complex of unfavorable electrostatic effects of the dianionic 5'
      phosphate of the FMN on the stability of the flavin hydroquinone anion. In this
      study, 15N and 1H-15N heteronuclear single-quantum coherence nuclear magnetic
      resonance spectroscopic studies demonstrate that when bound to the flavodoxin,
      (1) the N1 of the riboflavin hydroquinone remains anionic at pH 7.0 so the
      protonation of the hydroquinone is not responsible for this increase, (2) the N5
      position is much more exposed and may be hydrogen bonded to solvent, and (3) that
      while the hydrogen bonding interaction at the N3H appears stronger, that at the
      N5H in the reduced riboflavin is substantially weaker than for the native FMN
      complex. Thus, the higher reduction potential of the riboflavin complex is
      primarily the consequence of altered interactions with the flavin ring that
      affect hydrogen bonding with the N5H that disproportionately destabilize the
      semiquinone state of the riboflavin rather than through the absence of the
      electrostatic effects of the 5'-phosphate on the hydroquinone state.

PMID- 11245796
TI  - Reversible ischemic inhibition of F(1)F(0)-ATPase in rat and human myocardium.
AB  - The physiological role of F(1)F(0)-ATPase inhibition in ischemia may be to retard
      ATP depletion although views of the significance of IF(1) are at variance. We
      corroborate here a method for measuring the ex vivo activity of F(1)F(0)-ATPase
      in perfused rat heart and show that observation of ischemic F(1)F(0)-ATPase
      inhibition in rat heart is critically dependent on the sample preparation and
      assay conditions, and that the methods can be applied to assay the ischemic and
      reperfused human heart during coronary by-pass surgery. A 5-min period of
      ischemia inhibited F(1)F(0)-ATPase by 20% in both rat and human myocardium. After
      a 15-min reperfusion a subsequent 5-min period of ischemia doubled the inhibition
      in the rat heart but this potentiation was lost after 120 min of reperfusion.
      Experiments with isolated rat heart mitochondria showed that ATP hydrolysis is
      required for effective inhibition by uncoupling. The concentration of oligomycin
      for 50% inhibition (I(50)) for oxygen consumption was five times higher than its
      I(50) for F(1)F(0)-ATPase. Because of the different control strengths of F(1)F(0)
      ATPase in oxidative phosphorylation and ATP hydrolysis an inhibition of the
      F(1)F(0)-ATPase activity in ischemia with the resultant ATP-sparing has an
      advantage even in an ischemia/reperfusion situation.

PMID- 11245797
TI  - Identification of Lhcb1/Lhcb2/Lhcb3 heterotrimers of the main light-harvesting
      chlorophyll a/b-protein complex of Photosystem II (LHC II).
AB  - Using non-denaturing isoelectric focusing in polyacrylamide vertical slab gel, we
      have purified to homogeneity three trimeric subcomplexes of LHC II from
      Arabidopsis thylakoid membranes. The polypeptide composition of the subcomplexes
      were studied by immunoblotting. Our results indicate the existence in vivo of LHC
      II heterotrimers containing Lhcb1, Lhcb2 and Lhcb3 gene products.

PMID- 11245798
TI  - Heterocyclic ortho-quinones, a novel type of Photosystem II inhibitors.
AB  - Members of the new chemical class of 7-substituted 6-bromo
      benzo[4,5]imidazo[1,2alpha]pyridin-8,9-diones were found to be excellent
      inhibitors at the Q(B) site of the photosystem II D1 reaction center protein. The
      best inhibitors with pI(50)-values of >7 are: dimethyl-propyl, 7.05; i-pentyl,
      7.36; t. butyl, 7.47; and i-propyl, 7.51. Displacement experiments with
      [14C]atrazine revealed that the 8,9-diones behave non-competitively in respect of
      Photosystem II herbicides and, hence, have to be considered as a new type of
      Photosystem II inhibitors. This notion is further corroborated by their
      inhibitory activity in D1 mutants of Chlamydomonas reinhardtii.

PMID- 11245799
TI  - Transmembrane orientation and topology of the NADH:quinone oxidoreductase
      putative quinone binding subunit NuoH.
AB  - NADH:quinone oxidoreductase, or Complex I, is a multi-subunit membrane-bound
      enzyme in the respiratory chain of many pro- and eukaryotes. The enzyme catalyzes
      the oxidation of NADH and donates electrons to the quinone pool, coupled to
      proton translocation across the membrane, but the mechanism of energy
      transduction is not understood. In bacteria the enzyme consists of 14 subunits,
      seven membrane spanning and seven protruding from the membrane. The hydrophobic
      NuoH (NQO8, ND1, NAD1, NdhA) subunit is seemingly involved in quinone binding. A
      homologous, structurally and most likely functionally similar subunit is also
      found in F(420)H2 oxidoreductases and in complex membrane-bound hydrogenases. We
      have made theoretical analyses of NuoH and NuoH-like polypeptides and
      experimentally analyzed the transmembrane topology of the NuoH subunit from
      Rhodobacter capsulatus by constructing and analyzing alkaline phosphatase fusion
      proteins. This demonstrated that the NuoH polypeptide has eight transmembrane
      segments, and four highly conserved hydrophilic sequence motifs facing the
      inside, bacterial cytoplasm. The N-terminal and C-terminal ends are located on
      the outside of the membrane. A topology model of NuoH based on these results is
      presented, and implications from the model are discussed.

PMID- 11245800
TI  - Efficient large scale purification of his-tagged proton translocating
      NADH:ubiquinone oxidoreductase (complex I) from the strictly aerobic yeast
      Yarrowia lipolytica.
AB  - Proton translocating NADH:ubiquinone oxidoreductase (complex I) is the largest
      membrane bound multiprotein complex of the respiratory chain and the only one for
      which no molecular structure is available so far. Thus, information on the
      mechanism of this central enzyme of aerobic energy metabolism is still very
      limited. As a new approach to analyze complex I, we have recently established the
      strictly aerobic yeast Yarrowia lipolytica as a model system that offers a
      complete set of convenient genetic tools and contains a complex I that is stable
      after isolation. For crystallization of complex I and to obtain its molecular
      structure it is a prerequisite to prepare large amounts of highly pure enzyme.
      Here we present the construction of his-tagged complex I that for the first time
      allows efficient affinity purification. Our protocol recovers almost 40% of
      complex I present in Yarrowia mitochondrial membranes. Overall, 40-80 mg highly
      pure and homogeneous complex I can be obtained from 10 l of an overnight Y.
      lipolytica culture. After reconstitution into asolectin proteoliposomes, the
      purified enzyme exhibits full NADH:ubiquinone oxidoreductase activity, is fully
      sensitive to inhibition by quinone analogue inhibitors and capable of generating
      a proton-motive force.

PMID- 11245801
TI  - Origin and properties of fluorescence emission from the extrinsic 33 kDa
      manganese stabilizing protein of higher plant water oxidizing complex.
AB  - The fluorescence properties of the isolated extrinsic 33 kDa subunit acting as
      'manganese stabilizing protein' (MSP) of the water oxidizing complex in
      photosynthesis was analyzed in buffer solution. Measurements of the emission
      spectra as a function of excitation wavelength, pH and temperature led to the
      following results: (a) under all experimental conditions the spectra monitored
      were found to be the composite of two contributions referred to as '306 nm band'
      and 'long-wavelength band', (b) the excitation spectra of these two bands closely
      resemble those of tyrosine and tryptophan in solution, respectively, (c) the
      spectral shape of the '306 nm band' is virtually independent on pH but its
      amplitude drastically decreases in the alkaline with a pK of 11.7, (d) the
      amplitude of the 'long-wavelength' emission band at alkaline pH slightly
      increases when the pH rises from 7.2 to about 11.3 followed by a sharp decline at
      higher pH, and (e) the shape of the overall spectrum at pH 7.2 is only slightly
      changed upon heating to 90 degrees C whereas the amplitude significantly
      declines. Based on these findings the two distinct fluorescence bands are
      ascribed to tyrosine(s) ('306 nm band') and the only tryptophan residue W241 of
      MSP from higher plants ('long-wavelength band') as emitters which are both
      embedded into a rather hydrophobic environment.

PMID- 11245803
TI  - Changes of absorption spectra during heat-induced denaturation of Photosystem II
      core antenna complexes CP43 and CP47: revealing the binding states of chlorophyll
      molecules in these two complexes.
AB  - The Photosystem II (PSII) core antenna complexes, CP43 and CP47, were prepared
      from spinach (Spinacia oleracea L.). The absorption spectra in the red region at
      room temperature were recorded for the PSII core antenna samples after increased
      temperature treatment (up to 80 degrees C). Derivative and difference spectra
      revealed the existence of two groups of chlorophyll a (Chl a) molecules in both
      CP43 and CP47. The one with the absorption peak in the shorter wavelength region
      was designated as CP43-669 and CP47-669, while the other with the absorption peak
      in the longer wavelength region was designated as CP43-682 and CP47-680. The
      results of the thermal treatment experiment demonstrated that CP43-669 and CP47
      669 may exist as monomers of Chl a and that their binding sites on the
      polypeptides are insensitive to thermal treatment, whereas CP43-682 and CP47-680
      may exist as dimers or multimers of Chl a and their binding regions in the
      polypeptide chains are more sensitive to heat treatment. The excitation energy
      transfer mechanism between these two different groups of Chl a molecules is also
      analyzed.

PMID- 11245802
TI  - Functional complexes of mitochondria with Ca,MgATPases of myofibrils and
      sarcoplasmic reticulum in muscle cells.
AB  - Regulation of mitochondrial respiration in situ in the muscle cells was studied
      by using fully permeabilized muscle fibers and cardiomyocytes. The results show
      that the kinetics of regulation of mitochondrial respiration in situ by exogenous
      ADP are very different from the kinetics of its regulation by endogenous ADP. In
      cardiac and m. soleus fibers apparent K(m) for exogenous ADP in regulation of
      respiration was equal to 300-400 microM. However, when ADP production was
      initiated by intracellular ATPase reactions, the ADP concentration in the medium
      leveled off at about 40 microM when about 70% of maximal rate of respiration was
      achieved. Respiration rate maintained by intracellular ATPases was suppressed
      about 20-30% during exogenous trapping of ADP with excess pyruvate kinase (PK, 20
      IU/ml) and phosphoenolpyruvate (PEP, 5 mM). ADP flux via the external PK+PEP
      system was decreased by half by activation of mitochondrial oxidative
      phosphorylation. Creatine (20 mM) further activated the respiration in the
      presence of PK+PEP. It is concluded that in oxidative muscle cells mitochondria
      behave as if they were incorporated into functional complexes with adjacent ADP
      producing systems - with the MgATPases in myofibrils and Ca,MgATPases of
      sarcoplasmic reticulum.

PMID- 11245804
TI  - The manganese stabilizing protein (MSP) and the control of O2 evolution in the
      unicellular, diazotrophic cyanobacterium, Cyanothece sp. ATCC 51142.
AB  - The unicellular diazotrophic cyanobacterium, Cyanothece sp. ATCC 51142 temporally
      separates N2 fixation from photosynthesis. To better understand the processes by
      which photosynthesis is regulated, we have analyzed Photosystem (PS) II O2
      evolution and the PSII lumenal proteins, especially the Mn stabilizing protein
      (MSP). We describe a procedure using glycine betaine to isolate photosynthetic
      membranes from Cyanothece sp. that have high rates of PSI and PSII activity.
      Analysis with these membranes demonstrated similar patterns of O2 evolution in
      vivo and in vitro, with a trough at the time of maximal N2 fixation and with a
      peak in the late light period. The pattern of PSI activity was also similar in
      vivo and in vitro. We cloned the genes for MSP (psbO) and the 12 kDa protein
      (psbU) and analyzed their transcriptional properties throughout the diurnal
      cycle. We suggest that the changes in PSII activity in Cyanothece sp. were due to
      conformational changes in a highly flexible MSP, a suggestion which can now be
      studied in a chimera. The Cyanothece sp. psbO gene has been transformed into
      Synechocystis sp. PCC 6803; MSP and O2 evolution in the resulting transformant
      had properties that were similar to those in Cyanothece sp., providing additional
      confirmation for the properties of Cyanothece sp. MSP.

PMID- 11245805
TI  - Plasma membrane electron transport coupled to Na(+) extrusion in the halotolerant
      alga Dunaliella.
AB  - The halotolerant alga Dunaliella adapts to exceptionally high salinity and
      maintains low [Na(+)](in) at hypersaline solutions, suggesting that it possesses
      efficient mechanisms for regulating intracellular Na(+). In this work we examined
      the possibility that Na(+) export in Dunaliella is linked to a plasma membrane
      electron transport (redox) system. Na(+) extrusion was induced in Dunaliella
      cells by elevation of intracellular Na(+) with Na(+)-specific ionophores.
      Elevation of intracellular Na(+) was found to enhance the reduction of an
      extracellular electron acceptor ferricyanide (FeCN). The quinone analogs NQNO and
      dicumarol inhibited FeCN reduction and led to accumulation of Na(+) by inhibition
      of Na(+) extrusion. These inhibitors also diminished the plasma membrane
      potential in Dunaliella. Anaerobic conditions elevated, whereas FeCN partially
      decreased intracellular Na(+) content. Cellular NAD(P)H level decreased upon
      enhancement of plasma membrane electron transport. These results are consistent
      with the operation of an electrogenic NAD(P)H-driven redox system coupled to
      Na(+) extrusion in Dunaliella plasma membrane. We propose that redox-driven Na(+)
      extrusion and recycling in Dunaliella evolved as means of adaptation to
      hypersaline environments.

PMID- 11245806
TI  - Accessibility of tyrosine Y(.)(Z) to exogenous reductants and Mn(2+) in various
      Photosystem II preparations.
AB  - The reduction of tyrosine Y(.)(Z) by benzidine and exogenous Mn(2+) was studied
      by kinetic EPR experiments in various Photosystem II (PSII) preparations. Using
      lanthanide treated PSII membranes it was demonstrated that neither the extrinsic
      polypeptides (17, 23 and 33 kDa) nor the Mn complex block the accessibility of
      Y(.)(Z) to exogenous reductants, such as benzidine. In addition, it was shown
      that in the presence of the native Mn complex exogenous Mn(2+) does not reduce
      Y(.)(Z).

PMID- 11245807
TI  - Adenylate kinase activity in rod outer segments of bovine retina.
AB  - The rod outer segments of bovine retina contain two different adenylate kinases:
      a soluble activity, which is not sensitive to calcium ion, and an activity bound
      to disk membranes, which is dependent on the calcium levels. In fact, the maximal
      activity associated to the disks is reached at Ca(2+) concentrations between 10(
      6) and 10(-7) M, which is the range of calcium level actually present in the rod
      cell. The Michaelis-Menten kinetics of the enzyme activity on disk membranes was
      determined and the actual concentrations of ATP, AMP and ADP were measured in the
      photoreceptor outer segment. Therefore, the physiological relevance of the
      adenylate kinase activity was discussed considering the above results. The
      formation of ATP catalyzed by the enzyme seems appropriate to supply at least
      some of the reactions necessary for phototransduction, indicating that ATP could
      be regenerated from ADP directly on the disk membranes where the photoreception
      events take place.

PMID- 11245808
TI  - The energy level scheme for the ferryl heme in compound II of the peroxidase
      catalase family as determined from analysis of low-temperature magnetic circular
      dichroism.
AB  - The expressions for temperature-dependent magnetic circular dichroism (MCD) of
      the ferryl heme (Fe(4+)Por, S=1), which is a model of an intermediate product of
      the catalytic cycle of heme enzymes (compound II), have been derived in the
      framework of a two-term model. Theoretical predictions for the temperature and
      magnetic field dependence of MCD intensity of the ferryl heme are compared with
      those of the high-spin and low-spin ferric heme. Analysis of reported MCD spectra
      of myoglobin peroxide [Foot et al., Biochem. J. 2651 (1989) 515-522] and compound
      II of horseradish peroxidase [Browett et al., J. Am. Chem. Soc. 110 (1987) 3633
      3640] has shown the presence in the samples of approximately 1% of a low-spin
      ferric component, which, however, should be taken into account in simulating
      observed temperature dependences of MCD intensity. The values of two adjustable
      parameters are estimated from the fit of the observed and simulated plots of MCD
      intensity against the reciprocal of the absolute temperature. One of them, the
      energy gap between the ground and excited terms, predetermines the axial zero
      field splitting. The other parameter is correlated with the energy of splitting
      of excited quartets arising from either the porphyrin pi-->pi* transition or the
      spin-allowed charge-transfer transition.

PMID- 11245809
TI  - Expression of bone morphogenetic protein-6 and transforming growth factor-beta1
      in the rat brain after a mild and reversible ischemic damage.
AB  - We have examined the distribution of transforming growth factor-beta1 (TGF-beta1)
      and bone morphogenetic protein-6 (BMP-6) in the brain of rats subjected to a mild
      and reversible ischemic damage produced by a 20-min occlusion of both carotid
      arteries without occlusion of the vertebral arteries. We have selected this model
      to study how the expression of trophic factor of the TGF-beta superfamily changes
      in neurons that recover from a transient insult. Immunocytochemical analysis
      showed a loss of TGF-beta1 in neurons of all hippocampal subfields immediately
      after the ischemic period, followed by a recovery of immunoreactivity in CA1 and
      CA3 neurons after reperfusion. BMP-6 immunoreactivity was also lost in most
      hippocampal neurons, but immunostaining became particularly intense in the
      interstitial space after both ischemia and reperfusion. An interstitial
      localization of BMP-6 was also observed in the cerebral cortex, particularly
      after reperfusion. Mild ischemia also induced substantial changes in the
      expression of TGF-beta1 and BMP-6 within the cerebellar cortex. In control
      animals, these factors appeared to be localized in granule cells (TGF-beta1) and
      Purkinje cells (both), whereas the molecular layer was not immunopositive. Both
      TGF-beta1 and BMP-6 were highly expressed in the interstitial spaces of the
      cerebellar cortex either 20 min after ischemia or 20 min after reperfusion. Taken
      collectively, these results suggest that a mild and reversible ischemia
      stimulates the release of BMP-6 from neurons into the interstitial space. We
      speculate that BMP-6, besides functioning during brain development, may also
      regulate neuronal resistance to insults of the adult brain.

PMID- 11245810
TI  - Biotinylated m4-toxin demonstrates more M4 muscarinic receptor protein on direct
      than indirect striatal projection neurons.
AB  - The striatum has nearly equal numbers of striatonigral and striatopallidal
      projection neurons. All are GABAergic and inhibitory, but they lie in separate
      neuronal circuits ('direct' and 'indirect', respectively) that appear to exert
      opposite effects on movement. Methods are needed to evaluate the function of each
      circuit. A potential way to control striatonigral neurons selectively is via M4
      muscarinic receptors. The striatum has many more M4 receptors than other tissues,
      they are located on approximately half of all projection neurons, and mRNA for M4
      receptors is prevalent only in striatonigral neurons. In order to more rigorously
      compare the distribution of M4 receptors on rat neurons in these pathways a toxin
      that binds with very high specificity to M4 receptors (m4-toxin) was biotinylated
      for use as a selective probe for M4 receptor protein. Pooled biotin-toxin
      complexes were found to retain high M4-specificity and affinity. Neurons were
      first labeled by retrograde transport of fluorescent microbeads (FluoSpheres)
      injected into the substantia nigra and globus pallidus. Coincident labeling of
      only 4% of the cells confirmed the validity of the retrograde labeling technique.
      Labeled neurons were probed for M4 receptor protein using biotinylated m4-toxin
      and fluorescent avidin. M4 receptors were found on 14% of indirect and 86% of
      direct neurons. It may be concluded that there is a relative abundance of M4
      receptors controlling the direct pathway. This work supports the hypothesis that
      M4-selective drugs will prove useful to control the function of striatonigral
      neurons in the direct projection pathway.

PMID- 11245811
TI  - Beta-amyloid-induced glial expression of both pro- and anti-inflammatory
      cytokines in cerebral cortex of aged transgenic Tg2576 mice with Alzheimer plaque
      pathology.
AB  - To elucidate the mechanisms involved in beta-amyloid-mediated inflammation in
      Alzheimer's disease, transgenic Tg2576 mice containing as transgene the Swedish
      double mutation of human amyloid precursor protein 695, were examined for the
      expression pattern of various cytokines using double immunocytochemistry and
      laser scanning microscopy. Tg2576 mice studied at postnatal ages of 13, 16 and 19
      months demonstrated an age-related accumulation of both senile and diffuse beta
      amyloid plaques in neocortex and hippocampus. Reactive interleukin (IL)-1beta
      immunoreactive astrocytes were found in close proximity to both fibrillary and
      diffuse beta-amyloid deposits detectable at very early stages of plaque
      development, while activated microglia appeared in and around fibrillary beta
      amyloid plaques only. Subpopulations of reactive astrocytes also demonstrated
      immunolabeling for transforming growth factor (TGF)-beta1, TGF-beta3, and IL-10,
      already detectable in 13-month-old transgenic mouse brain, while a few IL-6
      immunoreactive astrocytes were observed only at later stages of plaque
      development. The early beta-amyloid-mediated upregulation of IL-1beta, TGF-beta,
      and IL-10 in surrounding reactive astrocytes indicates the induction of both pro-
      and anti-inflammatory mechanisms. The transgenic approach used in this study may
      thus provide a useful tool to further disclose the in vivo mechanisms by which
      pro- and anti-inflammatory cytokines interact and/or contribute to the
      progression of Alzheimer's disease.

PMID- 11245812
TI  - Prolonged exposure to hypobaric hypoxia transiently reduces GABA(A) receptor
      number in mice cerebral cortex.
AB  - The central nervous system is severely affected by hypoxic conditions, which
      produce alterations in neural cytoarchitecture and neurotransmission, resulting
      in a variety of neuropathological conditions such as convulsive states,
      neurobehavioral impairment and motor CNS alterations. Some of the
      neuropathologies observed in hypobaric hypoxia, corresponding to high altitude
      conditions, have been correlated with a loss of balance between excitatory and
      inhibitory neurotransmission, produced by alterations in glutamatergic and
      GABAergic receptors. In the present work, we have studied the effect of chronic
      hypobaric hypoxia (506 hPa, 18 h/day x 21 days) applied to adult male mice on
      GABA(A) receptors from cerebral cortex, to determine whether hypoxic exposure may
      irreversibly affect central inhibitory neurotransmission. Saturation curves for
      [3H]GABA specifically bound to GABA(A) receptors in isolated synaptic membranes
      showed a 30% decrease in maximal binding capacity after hypoxic exposure (Bmax
      control, 4.70+/-0.19, hypoxic, 3.33+/-0.10 pmol/mg protein), with no effect on
      GABA binding sites affinity (Kd control: 159.3+/-13.3 nM, hypoxic: 164.2+/-15.1
      nM). Decreased B(max) values were observed up to the 10th post-hypoxic day,
      returning to control values by the 15th post-hypoxic day. Pharmacological
      properties of GABA(A) receptor were also affected by hypoxic exposure, with a 45
      to 51% increase in the maximal effect by positive allosteric modulators
      (pentobarbital and 5alpha-pregnan-3alpha-ol-20-one). We conclude that long-term
      hypoxia produces a significant but reversible reduction on GABA binding to
      GABA(A) receptor sites in cerebral cortex, which may reflect an adaptive response
      to this sustained pathophysiological state.

PMID- 11245813
TI  - Metallothionein III is reduced in Alzheimer's disease.
AB  - Metallothionein III (MT-III) is a functionally distinct member of the
      metallothionein family that displays neuroinhibitory activity and is involved in
      the repair of neuronal damage. Altered expression levels of MT-III have been
      observed in Alzheimer's disease (AD) which has led to suggestions that it could
      be a mitigating factor in AD-related neuronal dysfunction. However, conflicting
      results have been reported on this issue which may be due to methodological
      differences and/or sampling size. In the current study, we have assessed MT-III
      expression in a large number of AD cases through the quantification of mRNA as
      well as by immunohistochemistry and Western blotting using an MT-III specific
      antibody. The results of this comprehensive study indicate that the
      mononucleosome DNA encoding MT-III is occluded preventing transcription and that
      message levels are reduced by approximately 30%. In addition, protein levels were
      specifically decreased by approximately 55% in temporal cortex. These data
      support the conclusion that MT-III is significantly downregulated in AD and may
      contribute to the loss of its protective effects and/or repair functions that
      lead to an exacerbation of the pathogenic processes.

PMID- 11245814
TI  - Intraventricular administration of the neurotrophic factor midkine ameliorates
      hippocampal delayed neuronal death following transient forebrain ischemia in
      gerbils.
AB  - Midkine (MK) is a growth factor with neurotrophic activities, and is expressed
      during the early stages of experimental cerebral infarction in rats in the zone
      surrounding the infarct. To evaluate in vivo activity of MK in preventing
      neuronal death, MK produced in yeast (Pichia pastoris) was administered into the
      brain ventricle immediately before occlusion of the bilateral common carotid
      artery of Mongolian gerbils. MK administration at the dose of 0.5-2 microg
      immediately before occlusion was found to ameliorate delayed neuronal death in
      the hippocampal CA1 region caused by transient ischemia 7 days after the insult.
      The hippocampal neurons of the MK-administered gerbils tended to degenerate 14
      and 21 days after the insult, but their numbers remained higher than those in
      saline-administered controls; however, the hippocampal neurons were degenerated
      28 days after the insult. MK administration at 2 h after occlusion did not
      ameliorate the neuronal death. These findings suggested that the therapeutic time
      window was narrow. The two to four times repeated administration of 2 microg MK
      immediately before and at 1, 2, or 3 weeks after the occlusion were not
      significantly different for the hippocampal neuronal death at 28 days after the
      insult compared with a single injection, but were significantly effective
      compared with vehicle administration alone. These findings suggested that the
      therapeutic time window was relatively narrow. The potent neuroprotective
      activity of MK observed in vivo suggested that MK might be useful as a
      therapeutic reagent for prevention of neuronal death in neurodegenerative
      diseases.

PMID- 11245815
TI  - Hippocampal neurons exhibit both persistent Ca2+ influx and impairment of Ca2+
      sequestration/extrusion mechanisms following excitotoxic glutamate exposure.
AB  - Exposure of neurons to glutamate is an essential element of neuronal function,
      producing transient elevations in free intracellular calcium ([Ca2+]i) that are
      required for normal physiological processes. However, prolonged elevations in
      [Ca2+]i have been observed following glutamate excitotoxicity and have been
      implicated in the pathophysiology of delayed neuronal cell death. In the current
      study, we utilized indo-1 and fura-2ff Ca2+ imaging techniques to determine if
      glutamate-induced prolonged elevations in [Ca2+]i were due to persistent influx
      of extracellular Ca2+ or from impairment of neuronal Ca2+ extrusion/sequestration
      mechanisms. By experimentally removing Ca2+ from the extracellular solution
      following glutamate exposure, influx of Ca2+ into the neurons was severely
      attenuated. We observed that brief glutamate exposures (<5 min, 50 microM
      glutamate) resulted in a Ca2+ influx that continued after the removal of
      glutamate. The Ca2+ influx was reversible, and the cell was able to effectively
      restore [Ca2+]i to resting levels. Longer, excitotoxic glutamate exposures (> or
      = 5 min) generated a Ca2+ influx that continued for the duration of the recording
      period (>1 h). This persistent Ca2+ influx was not primarily mediated through
      traditionally recognized Ca2+ channels such as glutamate receptor-operated
      channels or voltage-gated Ca2+ channels. In addition to the persistent Ca2+
      influx, longer glutamate exposures also produced a lasting disruption of Ca2+
      extrusion/sequestration mechanisms, impairing the ability of the neuron to
      restore resting [Ca2+]i. These data suggest that glutamate-induced protracted
      [Ca2+]i elevations result from at least two independent, simultaneously occurring
      alterations in neuronal Ca2+ physiology, including a persistent Ca2+ influx and
      damage to Ca2+ regulation mechanisms.

PMID- 11245816
TI  - Pharmacological evidence that alpha-ketoisovaleric acid induces convulsions
      through GABAergic and glutamatergic mechanisms in rats.
AB  - Neurological dysfunction is common in patients with maple syrup urine disease
      (MSUD). However, the mechanisms underlying the pathophysiology of this disorder
      are poorly known. In the present study we investigated the effect of
      intrastriatal administration of the alpha-keto acids accumulating in MSUD on the
      behavior of adult rats. After cannula placing, rats received unilateral
      intrastriatal injections of alpha-ketoisocaproic acid (KIC, 8 micromol), alpha
      ketoisovaleric acid (KIV, 8 micromol), alpha-keto-beta-methylvaleric acid (KMV, 6
      micromol) or NaCl. KIV elicited clonic convulsions in a dose-response manner,
      whereas KIC and KMV did not induce seizure-like behavior. Convulsions provoked by
      KIV were prevented by intrastriatal preadministration of muscimol (46 pmol) and
      MK-801 (3 nmol), but not by the preadministration of DNQX (8 nmol). These results
      indicate that among the keto acids that accumulate in MSUD, KIV is the only
      metabolite capable of causing convulsions in the present animal model and
      indicates that KIV is an important excitatory metabolite. Moreover, the
      participation of GABAergic and glutamatergic NMDA mechanisms in the KIV-induced
      convulsant behavior is suggested, since KIV-induced convulsions are attenuated by
      muscimol and MK-801. The authors suggest that KIV may play an important role in
      the convulsions observed in MSUD, and highlight its relevance to the
      understanding of the pathophysiology of the neurological dysfunction of MSUD
      patients.

PMID- 11245817
TI  - Amphetamine-stimulated cortical acetylcholine release: role of the basal
      forebrain.
AB  - Systemic administration of amphetamine results in increases in the release of
      acetylcholine in the cortex. Basal forebrain mediation of this effect was
      examined in three experiments using microdialysis in freely-moving rats.
      Experiment 1 examined whether dopamine receptor activity within the basal
      forebrain was necessary for amphetamine-induced increase in cortical
      acetylcholine by examining whether intra-basalis perfusion of dopamine
      antagonists attenuates this increase. Systemic administration of 2.0 mg/kg
      amphetamine increased dopamine efflux within the basal forebrain nearly 700%
      above basal levels. However, the increase in cortical acetylcholine efflux
      following amphetamine administration was unaffected by intra-basalis perfusions
      of high concentrations of D1- (100 microM SCH 23390) or D2-like (100 microM
      sulpiride) dopamine receptor antagonists. Experiments 2 and 3 determined whether
      glutamatergic or GABAergic local modulation of the excitability of the basal
      forebrain cholinergic neurons influences the ability of systemic amphetamine to
      increase cortical acetylcholine efflux. In Experiment 2, perfusion of kynurenate
      (1.0 mM), a non-selective glutamate receptor antagonist, into the basal forebrain
      attenuated the increase in cortical acetylcholine produced by amphetamine.
      Experiment 3 revealed that positive modulation of GABAergic transmission by
      bilateral intra-basalis infusion of the benzodiazepine receptor agonist
      chlordiazepoxide (40 microg/hemisphere) also attenuated the amphetamine
      stimulated increase in cortical acetylcholine efflux. These data suggest that
      amphetamine increases cortical acetylcholine release via a complex neuronal
      network rather than simply increasing basal forebrain D1 or D2 receptor activity.

PMID- 11245818
TI  - Dynamic changes in glucose metabolism accompanying the expression of the neural
      phenotype after differentiation in PC12 cells.
AB  - To assess what properties of glucose metabolism are most closely related to
      expression of the neural phenotype, some parameters of glucose metabolism in PC12
      cells before (tumor-type) and after differentiation (neuron-type) were
      investigated. Neuron-type cells exhibited a 2.7-fold higher level of [3H]DG
      retention than tumor-type cells, accompanied by a higher glucose transport rate
      and higher levels of hexokinase activity. [14C]CO2 production from [U-14C]glucose
      in neuron-type was also more than four-times greater than that in tumor-type
      cells. The levels of [14C]carbon in macromolecules from [14C]glucose in neuron
      type cells were also much higher (10.6-fold) than those in tumor-type cells, and
      the levels of incorporation of [14C]carbon were almost as high as those of
      [14C]CO2. From the metabolite analysis, amino acids appeared to be the major
      compounds converted from glucose. On the other hand, the uptakes of
      [35S]methionine-[35S]cysteine and [3H]uridine in neuron-type cells were lower
      than those in tumor-type cells. Following depolarization with 50 mM potassium,
      [14C]CO2 production increased, but the retention of [14C]carbon was not changed
      in neuron-type cells. The largest change accompanied by acquisition of the neural
      phenotype was carbon incorporation into the macromolecules derived from glucose.
      This property may be important for the expression of the neural phenotype as well
      as the higher levels of both glucose uptake and oxygen consumption.

PMID- 11245819
TI  - Development of tolerance to nicotine's anxiogenic effect in the social
      interaction test.
AB  - The purpose of the present experiment was to explore the role of the dorsal
      hippocampus in mediating the development of tolerance to the anxiogenic effect of
      nicotine in the social interaction test of anxiety, and to determine whether
      tolerance develops to the effects of nicotine on [3H]-5-HT release in this area.
      Nicotine (1 microg) administered bilaterally into the dorsal hippocampus
      significantly reduced the time spent in social interaction in vehicle pre-treated
      rats, indicating an anxiogenic effect, but tolerance to this effect was seen in
      the rats pre-treated for 6 days with s.c. nicotine (0.1 mg/kg/day). In rats that
      had been pre-treated with vehicle for 6 days, nicotine (50-200 microM),
      significantly stimulated [3H]-5-HT release from dorsal hippocampal slices. This
      stimulation was significantly reduced in rats pre-treated with nicotine (0.1
      mg/kg/day) for 6 days, indicating the development of tolerance to the effects of
      nicotine on 5-HT release. This suggests that tolerance to the anxiogenic effect
      of nicotine administered into the dorsal hippocampus could be mediated by a
      reduction in the nicotine enhancement of 5-HT release in this area.

PMID- 11245820
TI  - Is the AMPA receptor subunit GluR2 mRNA an early indicator of cell fate after
      ischemia? A quantitative single cell RT-PCR study.
AB  - After a moderate global cerebral ischemia, two hypothetical populations of
      pyramidal neurons are present among the hippocampal CA1 pyramidal neurons: one
      that will die and another one that will survive. Prior analysis of dissected
      hippocampal CA1 regions has shown a reduction of the GluR1-3 mRNA following
      ischemia. In order to identify these changes in single neurons, quantitative
      single cell RT-PCR was used to analyze the expression of GluR1-4 mRNA in rats 24
      h after ischemia and also in rats after tolerance inducing ischemia. Control CA1
      cells had a median copy-number of 290, 247, 207 and 16 GluR1-4, respectively. The
      tolerant cells showed small significant up-regulations of GluR1, 3 and 4 mRNA,
      while the GluR2 mRNA showed a more than 4-fold up-regulation compared to control
      cells. All the cells from ischemic animals displayed down-regulations of GluR1-3
      mRNA. The GluR4 mRNA was not detectable in the ischemic animals. Our results thus
      show that the CA1 neurons react uniformly 24 h after a moderate ischemia
      independent of the fate of the neuron: thus two neuron populations with different
      GluR2 profiles cannot be identified in post-ischemic animals at 24 h. It seems
      however that an increased level of GluR2 can be used as an indicator of tolerance
      to ischemia.

PMID- 11245821
TI  - Differential immunolocalization of m2 and m3 muscarinic receptors in the
      anteroventral and anterodorsal thalamic nuclei of the rat.
AB  - In this study, to identify the precise localization of m2 and m3 muscarinic
      receptors in the anteroventral and anterodorsal thalamic nuclei of the rat, we
      used receptor-subtype-specific antibodies and characterized their
      immunolocalization patterns by light and electron microscopy. Many m2-positive
      neurons were distributed throughout these nuclei. Ultrastructural analysis showed
      that more than 30% of m2-positive dendritic profiles in these nuclei are proximal
      dendritic shafts. Moreover, a few m2-positive fiber terminals were found only in
      the anterodorsal thalamic nucleus. These m2-positive terminals were large (1.10+/
      0.30 microm in diameter) and formed asymmetrical synapses with dendritic
      profiles. The m3-positive neurons were also distributed in both nuclei, and the
      m3-positive neuropil exhibited a significant staining gradient, with the most
      intense staining in the ventrolateral part of the anteroventral thalamic nucleus.
      This region receives the densest cholinergic input originating from the dorsal
      tegmental region. At the ultrastructural level, the majority of m3-positive
      dendritic profiles were more distal regions of the dendrites compared to the m2
      receptors in the anteroventral thalamic nucleus. However, no significant
      difference in the intradendritic distribution pattern between m2 and m3 receptors
      was found in the anterodorsal thalamic nucleus, which receives no cholinergic
      input. These findings show the differential localization of m2 and m3 receptors
      in the anteroventral and anterodorsal thalamic nuclei, and suggest that the m3
      receptors are spatially more closely associated with ascending cholinergic
      afferent fibers in the anteroventral thalamic nucleus.

PMID- 11245822
TI  - The temporal patterns of c-Fos and basic fibroblast growth factor expression
      following a unilateral anteromedial cortex lesion.
AB  - Following a unilateral anteromedial cortex lesion, a critical period of 12 h to 6
      days exists during which the recovery process is exquisitely vulnerable to
      manipulation. Certain anti-convulsant drugs, as well as convulsive seizures
      impede recovery when administered during, but not after, the critical period. The
      mechanisms underlying these behavioral phenomena have not been delineated. Thus,
      the present study was designed to determine potential mechanisms underlying and
      responsible for the critical period. To this end, we measured the
      immunoreactivity of two important markers of the post-injury response cascade, c
      Fos and bFGF, at designated times after a unilateral anteromedial cortex lesion.
      These temporal patterns of expression in the perilesional cortex and ipsilateral
      dorsal striatum were mapped onto functional recovery patterns. Within the
      critical period, c-Fos was dramatically elevated through 48 h after the lesion,
      while bFGF peaked later, on day 6. Upregulation of these markers preceded
      recovery from somatosensory deficits, which was most dramatic after post
      operative day 9 and complete by day 23. Early post-lesion expression of c-Fos may
      contribute to lesion-induced bFGF expression, which through its neurotrophic
      properties could be responsible for subsequent functional recovery. Gaining a
      similar understanding of the critical period following human traumatic brain
      injury could be an important first step toward improved treatment strategies and
      neurobehavioral outcome.

PMID- 11245823
TI  - Methylmercury inhibits the in vitro uptake of the glutathione precursor, cystine,
      in astrocytes, but not in neurons.
AB  - Maintenance of adequate intracellular glutathione (GSH) levels is vital for
      intracellular defense against oxidative damage. The toxic effects of
      methylmercury (MeHg) are attributable, at least in part, to elevated levels of
      reactive oxygen species, and thus decreases in GSH synthesis may increase
      methylmercury toxicity. Astrocytes have recently been proposed to play an
      essential role in providing GSH precursors to neurons. Therefore, cystine
      transport, a prerequisite to GSH production, was characterized in cultured
      astrocytes and neurons, and the effects of methylmercury on this transport were
      assessed. Astrocytes and neurons both possessed temperature dependent transport
      systems for cystine. Astrocytes accumulated cystine by Na+-independent (X(C)-)
      and -dependent (X(AG)-) systems while neurons used exclusively Na+-independent
      systems. Inhibition of the X(AG)- transport system decreased cystine transport in
      astrocytes to levels equivalent to those in sodium-depleted conditions,
      suggesting that cystine is carried by a glutamate/aspartate transporter in
      astrocytes. Inhibition of the multifunction ectoenzyme/amino acid transporter
      gamma-glutamyltranspeptidase (GGT) decreased cystine transport in both neurons
      and astrocytes. Inhibition of System X(C)- with quisqualate also decreased
      cystine uptake in both astrocytes and neurons. These data demonstrate that
      cultured astrocytes accumulate cystine via three independent mechanisms, System
      X(AG)-, System X(C)-, and GGT, while cultured hippocampal neurons use System X(C)
      and GGT exclusively. Inhibition of cystine uptake in astrocytes by methylmercury
      appears to be due to actions on the System X(AG)- transporter.

PMID- 11245824
TI  - NO synthesis inhibition decreases cortical ACh release and impairs retention of a
      conditioned response.
AB  - We investigated in rats the effect N(G)-nitro-L-arginine methyl ester (L-NAME) on
      retention of a passive avoidance response, and cortical ACh release monitored
      using the microdialysis technique. Post-training administration of L-NAME
      impaired 24 h retention of a passive avoidance and decreased cortical ACh
      release. Both effects of L-NAME were reversed by L-Arg. These results suggest
      that nitric oxide is involved in retention of the passive avoidance response
      through the modulation of the forebrain cholinergic system.

PMID- 11245825
TI  - Novel synthetic analogue of ACTH 4-10 (Semax) but not glycine prevents the
      enhanced nitric oxide generation in cerebral cortex of rats with incomplete
      global ischemia.
AB  - This work investigates whether nitric oxide production and lipid peroxidation
      contribute to the pathophysiology of ischemia and whether glycine and a novel
      Russian compound, Semax are neuroprotective via a mechanism involving the
      regulation nitric oxide (NO) and lipid peroxidation. In brief, nitric oxide and
      indices of lipid peroxidation were elevated following global ischemia. While
      glycine proved ineffective in reducing NO levels or ameliorating the neurological
      deficits following global ischemia, Semax proved to be highly effective in
      abating the rise in nitric oxide and restoring neurologic functioning.

PMID- 11245826
TI  - Attenuation of hyperalgesia by LY235959, a competitive N-methyl-D-aspartate
      receptor antagonist.
AB  - N-methyl-D-aspartate (NMDA) receptor antagonists may be of value in the
      management of hyperalgesia. LY235959, a competitive NMDA receptor antagonist, at
      doses of 0.001 and 0.003 nmol, intrathecally (i.t.) blocked the hyperalgesia
      induced by 11.1 nmol of NMDA in rats prepared with a chronic i.t. cannula.
      However, LY235959 does not block the hyperalgesia produced by kainic acid (a non
      NMDA glutamate receptor agonist) providing evidence of its selectivity for the
      NMDA receptor. Using the formalin nociceptive test, 0.001 nmol LY235959 (i.t.)
      significantly reduced the number of Phase 2 flinches by about 80%. LY235959 can
      also reduce the flinching in Phase 2 by 30% when given subcutaneously (s.c.) at
      the lowest dose which does not produce motor deficits (20 mmol/kg). Thus,
      LY235959 (i.t. or s.c.) has NMDA receptor antagonist activity as defined by its
      ability to prevent hyperalgesia and formalin-induced central sensitization.
      Moreover, it is a much more potent antihyperalgesic after i.t. as compared to
      s.c. administration.

PMID- 11245827
TI  - Prenatal morphine exposure alters estrogen regulation of kappa receptors in the
      cortex and POA of adult female rats but has no effects on these receptors in
      adult male rats.
AB  - The binding characteristics of kappa receptors were assessed in the frontal
      cortex (CX), striatum, hypothalamus, preoptic area (POA), cerebellum, and ventral
      tegmental area of adult male and female rats exposed prenatally to morphine or
      saline. Prenatal morphine exposure altered estrogen regulation of kappa receptors
      in the CX and POA of females, but had no effects on kappa receptors in any of the
      examined brain regions in male rats.

PMID- 11245830
TI  - Addition of hydrophilic and lipophilic compounds of biological relevance to the
      monoolein/water system II - 13C NMR relaxation study.
AB  - The addition of hydrophilic and hydrophobic molecules to the 1-monooleoyl
      glycerol (MO)/water (W) system has been investigated at a molecular level by 13C
      nuclear magnetic resonance (NMR) relaxation. Depending on the nature of the
      additive, the liquid crystalline phases of the MO/W binary system are modified.
      The 13C NMR spin lattice relaxation rates of the various MO carbons were
      determined in the presence of the additives for different types of L(2) and
      liquid crystalline phases. Data revealed that local dynamics are independent of
      type and amount of additive (within 5 wt.%), and also of the type of the
      structural arrangement. The curvature of the interface does not affect the local
      mobility of MO carbons, with the exception of the glycerol G3 and the carboxylic
      C1 carbons. Moreover, the presence of the double bond in the mid part of the
      hydrocarbon chain induces a levelling in the relaxation rates on the neighboring
      carbons. The 13C NMR spin lattice relaxation rates at two magnetic field
      strengths and the Overhauser enhancement were measured in the L(2) phase of the
      MO/W/sodium decanoate system. The use of a two-step model of relaxation allowed
      to estimate order parameters, and slow and fast motions of MO in the structured
      aggregate.

PMID- 11245829
TI  - Analysis of pulmonary surfactant by Fourier-transform infrared spectroscopy
      following exposure to Stachybotrys chartarum (atra) spores.
AB  - Lung cells are among the first tissues of the body to be exposed to air-borne
      environmental contaminants. Consequently the function of these cells may be
      altered before other cells are affected. As gas exchange takes place in the
      lungs, changes in cellular function may have serious implications for the
      processes of oxygen uptake and carbon dioxide elimination. In order for these
      processes to occur, the lung must maintain a high degree of expandability. This
      latter function is accomplished in part by the pulmonary surfactant which is
      synthesized and released by alveolar type II cells. Earlier studies have shown
      that exposure to gas phase materials such as smoke or organic solvents can alter
      the composition and function of the surfactant. The present study examines the
      ability of highly toxigenic mold spores to alter surfactant composition.
      Stachybotrys chartarum spores suspended in saline were instilled into mouse
      trachea as described earlier. After 24 h, the lungs were lavaged and the
      different processing stages of surfactant isolated by repeated centrifugation.
      Intracellular surfactant was isolated from the homogenized lung tissue by
      centrifugation on a discontinuous sucrose gradient. Samples were extracted into
      chloroform-methanol, dried and analyzed by Fourier-Transform infrared
      spectroscopy (FTIR). Exposure to S. chartarum induced an overall reduction of
      phospholipid among the three surfactant subfractions. The intermediate and spent
      surfactant fractions in particular were reduced to about half of the values
      observed in the saline-treated group. The relative distribution of phospholipid
      was also altered by spore exposure. Within the intracellular surfactant pool,
      higher levels of phospholipid were detected after spore exposure. In addition,
      changes were observed in the nature of the phospholipids. In particular strong
      intramolecular hydrogen bonding, together with other changes, suggested that
      spore exposure was associated with absence of an acyl chain esterified on the
      glycerol backbone, resulting in elevated levels of lysophospholipid in the
      samples. This study shows that mold spores and their products induce changes in
      regulation of both secretion and synthesis of surfactant, as well as alterations
      in the pattern of phospholipid targeting to the pulmonary surfactant pools.

PMID- 11245831
TI  - Use of a fluorescence spectroscopy technique to study the adsorption of sodium
      dodecylsulfonate on liposomes.
AB  - The fluorescent probe 2-(p-toluidinyl)-naphthalene-6-sodium sulfonate was used to
      study the surface adsorption of sublytic concentrations of the anionic surfactant
      sodium dodecylsulfonate (C(12)-SO(3)) on phosphatidylcholine bilayers. The number
      of adsorbed molecules was quantified by determination of the electrostatic
      potential (psi(0)) of the bilayers. The abrupt decrease in the fluorescence
      intensity already detected 10 s after the surfactant addition and the slight
      fluorescence variations with time indicated that the surfactant adsorption was
      very fast and almost complete. For a given number of monomers adsorbed, a linear
      dependence between the lipid and C(12)-SO(3) concentrations was obtained,
      indicating a similar adsorption mechanism regardless of the surfactant
      concentration. Hence, a monomeric adsorption is assumed even in systems with a
      C(12)-SO(3) concentration above its critical micellar concentration (CMC). In
      addition, this linear correlation allowed us to determine the surfactant/lipid
      molar ratios (Re) (inversely related to the C(12)-SO(3) ability to be adsorbed on
      liposomes) and the bilayer/aqueous phase coefficients (K). The fact that the
      lowest values for Re were always reached after 10 s of incubation corroborates
      the rapid kinetic of the process. The decrease in the C(12)-SO(3) partitioning
      (K) when the number of surfactant molecules exceeded 15000 was possibly due to
      the electrostatic repulsion between the free and the adsorbed monomers, which
      could hinder the incorporation of new monomers on the charged surface of
      liposomes.

PMID- 11245832
TI  - Curvature elasticity of multilamellar lipid bilayers close to the chain-melting
      transition.
AB  - We directly measured curvature elasticity of dipalmitoylphosphatidylcholine
      multilamellar bilayers close to the chain-melting transition using the method of
      electric-field-induced bending deformation of the cylindrical tubes. The result
      shows that the bending modulus, kappa(c), decreases remarkably at temperatures
      close to the melting transition temperature. This reflects a softening of the
      bilayer resulted from the area fluctuations as predicted theoretically. However,
      the decrease of kappa(c) near the transition is far smaller than that predicted.
      This is due to the experimental method and the narrow transition width of the
      multilamellar bilayers. Nevertheless, the result obtained gives direct evidence
      of the kappa(c) reduction predicted for multilamellar membranes in the transition
      regime. Below about 41 degrees C, almost of all cylindrical tubes cannot response
      to the electric field, indicating a very large bending rigidity.

PMID- 11245833
TI  - Chain length dependence of lipid partitioning between the air/water interface and
      its subphase: thermodynamic and structural implications.
AB  - We have investigated phosphatidylcholines with the same two saturated hydrocarbon
      chains of 12, 10 and 8 C-atoms. Langmuir trough data could be evaluated towards
      even small lipid subphase desorption when applying a novel approach that had
      recently been developed in our laboratory. The C12 lipid turned out to form a
      nearly insoluble monolayer with slight desorption only beyond 15 mN/m for an
      area/volume ratio around 1 cm(-1). Above 22 mN/m micellation in the subphase
      apparently terminates further accumulation in the interface forcing additionally
      added lipid to enter the bulk volume. A comparatively substantial increase of
      solubilization was observed for the C10 monolayer. When turning to the C8 lipid
      partitioning proved to take place in nearly equal parts. In that case, strong
      multimeric aggregation is indicated to occur in both the interfacial and the bulk
      volume domains. All the results are quantitatively discussed in the light of
      basic thermodynamic and structural considerations.

PMID- 11245834
TI  - Effect of the hydrophobic surfactant proteins on the surface activity of spread
      films in the captive bubble surfactometer.
AB  - The main function of pulmonary surfactant, a mixture of lipids and proteins, is
      to reduce the surface tension at the air/liquid interface of the lung. The
      hydrophobic surfactant proteins SP-B and SP-C are required for this process. When
      testing their activity in spread films in a captive bubble surfactometer, both SP
      B and SP-C showed concentration dependence for lipid insertion as well as for
      lipid film refinement. Higher activity in DPPC refinement of the monolayer was
      observed for SP-B compared with SP-C. Further differences between both proteins
      were found, when subphase phospholipid vesicles, able to create a monolayer
      attached lipid reservoir, were omitted. SP-C containing monolayers showed
      gradually increasing minimum surface tensions upon cycling, indicating that a
      lipid reservoir is required to prevent loss of material from the monolayer.
      Despite reversible cycling dynamics, SP-B containing monolayers failed to reach
      near-zero minimum surface tensions, indicating that the reservoir is required for
      stable films.

PMID- 11245835
TI  - Sequential substitution of 1,2-dichloro-ethene: a convenient stereoselective
      route to (9Z,11E)-, (10E,12Z)- and (10Z,12Z)-.
AB  - Conjugated linoleic acid (CLA) isomers are present in human foods derived from
      milk or ruminant meat. To study their metabolism, (9Z,11E)-, (10E,12Z)- and
      (10Z,12Z)-[1-(14)C]-octadecadienoic acids with high radiochemical and isomeric
      purities (>98%) were prepared by stereoselective multi-step syntheses involving
      sequential substitution of 1,2-dichloro-ethene. In the case of the (9Z,11E)
      isomer, a first metal-catalyzed cross-coupling reaction between (E)-1,2-dichloro
      ethene and 2-non-8-ynyloxy-tetrahydro-pyran, obtained from 7-bromo-heptan-1-ol,
      gave a conjugated chloroenyne. A second coupling reaction with hexylmagnesium
      bromide provided a heptadecenynyl derivative. Stereoselective reduction of the
      triple bond and bromination afforded (7E,9Z)-17-bromo-heptadeca-7,9-diene.
      Formation of the Grignard reagent and carbonation with 14CO(2) gave (9Z,11E)-[1
      (14)C]-octadeca-9,11-dienoic acid (overall yield from 7-bromo-heptan-1-ol,
      14.4%). (10E,12Z)- and (10Z,12Z)-[1-(14)C]-octadeca-10,12-dienoic acids were
      synthesized by the same methodology using 1-heptyne, 8-bromo-octan-1-ol and,
      respectively, (E)-1,2-dichloro-ethene and its (Z) isomer (overall yield from 8
      bromo-octan-1-ol, 13.1% (10E,12Z); 17.2% (10Z,12Z)). Impurities (<2% if present)
      were identified as being (E,E) CLA isomers and were removed by RP-HPLC.
      Metabolism studies in animal are in progress.

PMID- 11245837
TI  - Incorporation of plastoquinone and ubiquinone into liposome membranes studied by
      HPLC analysis. The effect of side chain length and redox state of quinone.
AB  - The efficiency of incorporation of plastoquinones and ubiquinones into
      phospholipid liposomes has been studied. The representatives of short (PQ1 and
      UQ1) middle (PQ4 and UQ4) and long (PQ9, UQ9 and UQ10) prenylquinones have been
      used to investigate the effect of quinone side chain length. The properties of
      hydroquinones have been also thoroughly examined in relation to the quinone
      forms. The extraction procedure was modified and further developed which enables
      removing of nonincorporated quinone by pentane washing and then determination of
      quinone content inside the lipid bilayer. The quantitatively evaluation of the
      amount of prenylquinone was assayed by means of HPLC analysis which offers much
      greater sensitivity and could be easily applied in case of hydroquinones. It has
      been found that PQ1 and UQ1 as well as their reduced forms were present mainly
      (about 80%) in the aqueous phase, when attempting to introduce them into
      phospholipid bilayer. In case of quinones having four and more isoprenyl units in
      side chain, a high level of quinone incorporation, ranging about 95%, was
      observed. The results pointed out that when comparing the effects of different
      exogenous quinones on membrane related processes, one has to consider the
      effectiveness of their incorporation within lipid bilayer.

PMID- 11245836
TI  - A comparative study of the ability of ferric nitrilotriacetate [correction of
      nitriloacetate] and other iron chelators to assist membrane lipid peroxidation by
      superoxide radicals.
AB  - This study examined some of the variables determining the efficiency of lipid
      peroxidation in egg yolk phosphatidylcholine liposomes and in microsomes exposed
      to enzymatically-generated superoxide radicals. The initiation of peroxidation
      required the presence of preformed lipid peroxides and a chelated metal catalyst.
      Comparison of the relative effectiveness of four iron chelating agents showed
      that the chelate must bind to the membrane by coulombic attraction between the
      charged membrane and a chelate carrying an opposite net charge. Of the chelates
      tested, only the carcinogenic ferric nitrilotriacetate [corrected] (Fe(3+)-NTA)
      was an effective catalyst of oxidation of all membranes, whether carrying a net
      charge, or not. We postulate that the unique catalytic capacity of the ferric
      nitrilotriacetate [corrected] (Fe(3+)-NTA) can be explained by its existence in
      two forms at neutral pH, each binding to oppositely charged membranes and
      initiating their peroxidation. This gives the complex the unique ability to bind
      to any membrane, which may be a factor in its carcinogenicity.

PMID- 11245838
TI  - Objects and attention: the state of the art.
AB  - What are the units of attention? In addition to standard models holding that
      attention can select spatial regions and visual features, recent work suggests
      that in some cases attention can directly select discrete objects. This paper
      reviews the state of the art with regard to such 'object-based' attention, and
      explores how objects of attention relate to locations, reference frames,
      perceptual groups, surfaces, parts, and features. Also discussed are the dynamic
      aspects of objecthood, including the question of how attended objects are
      individuated in time, and the possibility of attending to simple dynamic motions
      and events. The final sections of this review generalize these issues beyond
      vision science, to other modalities and fields such as auditory objects of
      attention and the infant's 'object concept'.

PMID- 11245839
TI  - Attention-based visual routines: sprites.
AB  - A central role of visual attention is to generate object descriptions that are
      not available from early vision. Simple examples are counting elements in a
      display or deciding whether a dot is inside or outside a closed contour (Ullman,
      Cognition 18 (1984) 97). We are interested in the high-level descriptions of
      dynamic patterns - the motions that characterize familiar objects undergoing
      stereotypical action - such as a pencil bouncing on a table top, a butterfly in
      flight, or a closing door. We examine whether the perception of these action
      patterns is mediated by attention as a high-level animation or 'sprite'. We have
      studied the discrimination of displays made up of simple, rigidly linked sets of
      points in motion: either pairs of points in orbiting motion or 11 points in
      biological motion mimicking human walking. We find that discrimination of even
      the simplest dynamic patterns demands attention.

PMID- 11245840
TI  - Segmentation, attention and phenomenal visual objects.
AB  - Issues concerning selective attention provoke new questions about visual
      segmentation, and vice-versa. We illustrate this by describing our recent work on
      grouping under conditions of inattention, on change blindness for background
      events and the residual processing of undetected background changes, on modal
      versus amodal completion in visual search, and the differential effects of these
      two forms of completion on attentional processes, and on attentional modulation
      of lateral interactions thought to arise in early visual cortex. Many of these
      results indicate that segmentation processes substantially constrain attentional
      processes, but the reverse influence is also apparent, suggesting an interactive
      architecture. We discuss how the 'proto-objects' revealed by studies of
      segmentation and attention (i.e. the segmented perceptual units which constrain
      selectivity) may relate to other object-based notions in cognitive science, and
      we wrestle with their relation to phenomenal visual awareness.

PMID- 11245841
TI  - Auditory and visual objects.
AB  - Notions of objecthood have traditionally been cast in visuocentric terminology.
      As a result, theories of auditory and cross-modal perception have focused more on
      the differences between modalities than on the similarities. In this paper we re
      examine the concept of an object in a way that overcomes the limitations of the
      traditional perspective. We propose a new, cross-modal conception of objecthood
      which focuses on the similarities between modalities instead of the differences.
      Further, we propose that the auditory system might consist of two parallel
      streams of processing (the 'what' and 'where' subsystems) in a manner analogous
      to current conceptions of the visual system. We suggest that the 'what'
      subsystems in each modality are concerned with objecthood. Finally, we present
      evidence for - and elaborate on - the hypothesis that the auditory 'where'
      subsystem is in the service of the visual-motor 'where' subsystem.

PMID- 11245842
TI  - Visual indexes, preconceptual objects, and situated vision.
AB  - This paper argues that a theory of situated vision, suited for the dual purposes
      of object recognition and the control of action, will have to provide something
      more than a system that constructs a conceptual representation from visual
      stimuli: it will also need to provide a special kind of direct (preconceptual,
      unmediated) connection between elements of a visual representation and certain
      elements in the world. Like natural language demonstratives (such as 'this' or
      'that') this direct connection allows entities to be referred to without being
      categorized or conceptualized. Several reasons are given for why we need such a
      preconceptual mechanism which individuates and keeps track of several individual
      objects in the world. One is that early vision must pick out and compute the
      relation among several individual objects while ignoring their properties.
      Another is that incrementally computing and updating representations of a dynamic
      scene requires keeping track of token individuals despite changes in their
      properties or locations. It is then noted that a mechanism meeting these
      requirements has already been proposed in order to account for a number of
      disparate empirical phenomena, including subitizing, search-subset selection and
      multiple object tracking (Pylyshyn et al., Canadian Journal of Experimental
      Psychology 48(2) (1994) 260). This mechanism, called a visual index or FINST, is
      briefly discussed and it is argued that viewing it as performing a demonstrative
      or preconceptual reference function has far-reaching implications not only for a
      theory of situated vision, but also for suggesting a new way to look at why the
      primitive individuation of visual objects, or proto-objects, is so central in
      computing visual representations. Indexing visual objects is also, according to
      this view, the primary means for grounding visual concepts and is a potentially
      fruitful way to look at the problem of visual integration across time and across
      saccades, as well as to explain how infants' numerical capacity might arise.

PMID- 11245843
TI  - What is a visual object? Evidence from target merging in multiple object
      tracking.
AB  - The notion that visual attention can operate over visual objects in addition to
      spatial locations has recently received much empirical support, but there has
      been relatively little empirical consideration of what can count as an 'object'
      in the first place. We have investigated this question in the context of the
      multiple object tracking paradigm, in which subjects must track a number of
      independently and unpredictably moving identical items in a field of identical
      distractors. What types of feature clusters can be tracked in this manner? In
      other words, what counts as an 'object' in this task? We investigated this
      question with a technique we call target merging: we alter tracking displays so
      that distinct target and distractor locations appear perceptually to be parts of
      the same object by merging pairs of items (one target with one distractor) in
      various ways - for example, by connecting item locations with a simple line
      segment, by drawing the convex hull of the two items, and so forth. The data show
      that target merging makes the tracking task far more difficult to varying degrees
      depending on exactly how the items are merged. The effect is perceptually
      salient, involving in some conditions a total destruction of subjects' capacity
      to track multiple items. These studies provide strong evidence for the object
      based nature of tracking, confirming that in some contexts attention must be
      allocated to objects rather than arbitrary collections of features. In addition,
      the results begin to reveal the types of spatially organized scene components
      that can be independently attended as a function of properties such as
      connectedness, part structure, and other types of perceptual grouping.

PMID- 11245844
TI  - Infants' knowledge of objects: beyond object files and object tracking.
AB  - Two independent research communities have produced large bodies of data
      concerning object representations: the community concerned with the infant's
      object concept and the community concerned with adult object-based attention. We
      marshal evidence in support of the hypothesis that both communities have been
      studying the same natural kind. The discovery that the object representations of
      young infants are the same as the object files of mid-level visual cognition has
      implications for both fields.

PMID- 11245845
TI  - Doxorubicin and mechanical performance of cardiac trabeculae after acute and
      chronic treatment: a review.
AB  - Doxorubicin, a very potent and often used anti-cancer drug, has a wide spectrum
      of biological activity. Classic studies have demonstrated that doxorubicin and
      other members of the anthracycline family intercalate with DNA and partially
      uncoil the double-stranded helix. Doxorubicin has a high affinity for cell
      nuclei: as much as 60% of the total intracellular amount of doxorubicin is found
      in the nucleus. Once binding to DNA occurs, several consequences may ensue. The
      binding of anthracyclines to DNA inhibits DNA polymerase and nucleic acid
      synthesis. In addition, anthracyclines are known to stabilize the otherwise
      cleavable complex between DNA and homodimeric topoisomerase II enzyme subunits,
      resulting in the formation of protein-linked DNA double strand breaks. In tumor
      cells, these anthracycline-induced perturbations are believed to result in a
      final common pathway of endonucleolytic DNA fragmentation known as apoptosis.
      Because proliferation is an important determinant of tumor growth, interference
      with the genome is regarded as the primary cause of the anti-tumor action of
      doxorubicin. Intercalation with DNA may not be important in the cardiotoxicity
      associated with doxorubicin therapy (see next section), because cardiac cell
      proliferation in humans stops after 2 months of age. This review is focussed on
      the effects of doxorubicin on mechanical performance in skinned cardiac
      trabeculae after acute and chronic administration of doxorubicin. We look
      especially at the mechanical performance and the molecular changes observed and
      related to mechanical performance.

PMID- 11245846
TI  - A23187 causes release of inositol phosphates from cultured rat Kupffer cells.
AB  - The Ca2+ ionophore A23187 is routinely used to illustrate the extracellular Ca2+
      dependence of a variety of cellular reactions. We found that A23187-induced
      hydrolysis of phosphoinositides to various inositol phosphates in rat Kupffer
      cells was accompanied by their release from the cells. The synthesis and release
      of inositol phosphates was A23187 concentration-dependent (0.5-10 microM), and
      was apparent at the lowest concentration tested. A23187-induced release of
      inositol phosphates increased time-dependently, was apparent at 5 s of
      stimulation and maximal at 20 min. The effects of A23187 were reversed by EGTA.
      The integrity of the cells was not affected by A23187 treatment as indicated by
      their exclusion of trypan blue and the lack of release of lactate dehydrogenase.
      We propose that such effects should be considered while evaluating the Ca2+
      dependence of biological processes based on the actions of A23187.

PMID- 11245847
TI  - Monoamine oxidase in developing rat renal cortex: effect of dexamethasone
      treatment.
AB  - The expression of the biogenic amine degrading enzyme monoamine oxidases-A and -B
      depends on several factors including regional distribution, development and
      hormonal environment. In the present study, we investigated the expression of
      monoamine oxidases in developing kidney and their regulation by dexamethasone
      treatment. Immunoblots and enzyme assays, performed using [14C]5
      hydroxytriptamine and [14C]beta-phenylethylamine as substrates for monoamine
      oxidases-A and -B, respectively, showed that monoamine oxidase-A is the isoenzyme
      largely predominant in 9-day-old rats renal cortex. Experiments performed in 5
      week-old rats showed an increase in monoamine oxidase-B activity and a decrease
      in monoamine oxidase-A activity and substrate affinity. The changes of monoamine
      oxidase-A activity and affinity were mimicked by dexamethasone treatment (0.60
      mg/kg body weight injected subcutaneously three times at intervals of 24 h) of 9
      day-old rats. In contrast, dexamethasone administration induced a modification of
      monoamine oxidase-B activity opposite to that found between 9-day- and 5-week-old
      rats. Dexamethasone treatment did not modify immunoreactivity and mRNA
      corresponding to monoamine oxidases-A and -B indicating that changes of enzyme
      activities were unrelated to regulation of protein synthesis and mRNA turnover.
      These results show that monoamine oxidases-A and -B are differently expressed in
      developing renal cortex and are regulated by dexamethasone treatment.

PMID- 11245848
TI  - Mechanisms involved in the blunted nitric oxide-cGMP pathway in hypertensive
      TGR(mREN2)27 rats.
AB  - In hypertensive TGR(mREN2)27 rats (TGR), the subsensitivity of vascular guanylyl
      cyclase to nitric oxide could depend on oxidized heme, reduced heme content, or
      decreased expression of the enzyme. In this study, enzyme activity was stimulated
      by protoporphyrin-IX, which acts independently of heme, and expression was
      assessed by Western blot analysis. In TGR aorta, maximum stimulation of soluble
      guanylyl cyclase by protoporphyrin-IX was 40% lower than in Sprague-Dawley
      controls, and expression of the beta1-subunit of the enzyme was reduced by 50%
      (P<0.05, t-test). In conclusion, decreased expression of soluble guanylyl cyclase
      leads to a blunted response of the nitric oxide-cGMP (guanosine 3',5'-cyclic
      monophosphate) pathway in TGR aorta.

PMID- 11245849
TI  - The role of delta-opioid receptor subtypes in neuropathic pain.
AB  - A large body of evidence suggests an important role of delta-opioid receptor
      agonists in antinociception at the level of the spinal cord. Our study was
      undertaken to analyse the spinal antinociceptive and antiallodynic effects of
      delta(1)- and delta(2)-opioid receptor agonists and antagonist after their acute
      and chronic intrathecal administration in a neuropathic pain model in the rat. In
      rats with a crushed sciatic nerve, the delta(1)-opioid receptor agonist [D
      Pen(2), D-Pen(5)]enkephalin (DPDPE, 5-25 microg i.t.) and the delta(2)-opioid
      receptor agonist deltorphin II (1.5-25 microg i.t.) dose dependently antagonized
      the cold-water allodynia which developed after sciatic nerve injury. These
      effects of DPDPE were antagonized by 7-benzylidenenaltrexon (BNTX, 1 microg i.t.)
      while the effects of deltorphin II were antagonized by 5'naltrindole
      izotiocyanate (5'NTII, 25 microg i.t.). Both agonists had a dose-dependent,
      statistically significant effect on the tail-flick latency in two tests, with
      focused light and cold water. Chronic administration of DPDPE (25 microg i.t.)
      and deltorphin II (15 microg i.t.) resulted in significant prolongation of the
      reaction time determined on days 2, 4 and 6 post-injury. In conclusion, our
      results show an antiallodynic and antinociceptive action of DPDPE and deltorphin
      II at the spinal cord level, which suggests that both delta-opioid receptor
      subtypes play a similar role in neuropathic pain. This indicates that not only
      delta(1)- but also delta(2)-opioid receptor agonists can be regarded as potential
      drugs for the therapy of neuropathic pain.

PMID- 11245850
TI  - Characterisation of the effects of a non-peptide CGRP receptor antagonist in SK-N
      MC cells and isolated human cerebral arteries.
AB  - The cerebral circulation is innervated by calcitonin gene-related peptide (CGRP)
      containing fibers originating in the trigeminal ganglion. During a migraine
      attack, there is a release of CGRP in conjunction with the head pain, and triptan
      administration abolishes both the CGRP release and the pain at the same time. In
      the search for a novel treatment of migraine, a non-peptide CGRP antagonist has
      long been sought. Here, we present data on a human cell line and human and guinea
      pig isolated cranial arteries for such an antagonist, Compound 1 (4-(2-Oxo-2,3
      dihydro-benzoimidazol-1-yl)-piperidine-1-carboxylic acid [1-(3,5-dibromo-4
      hydroxy-benzyl)-2-oxo-2-(4-phenyl-piperazin-1-yl)-ethyl]-amide). On SK-N-MC cell
      membranes, radiolabelled CGRP binding was displaced by both CGRP-(8-37) and
      Compound 1, yielding pK(i) values of 8.9 and 7.8, respectively. Functional
      studies with SK-N-MC cells showed that CGRP-induced cAMP production was
      antagonised by both CGRP-(8-37) and Compound 1 with pA(2) values of 7.8 and 7.7,
      respectively. Isolated human and guinea pig cerebral arteries were studied with a
      sensitive myograph technique. CGRP induced a concentration-dependent relaxation
      in human cerebral arteries which was antagonized by both CGRP-(8-37) and Compound
      1 in a competitive manner. In guinea pig basilar arteries, CGRP-(8-37)
      antagonised the CGRP-induced relaxation while Compound 1 had a weak blocking
      effect. The clinical studies of non-peptide CGRP antagonists are awaited with
      great interest.

PMID- 11245852
TI  - Growth hormone interferes with the progression of myocarditis in rats.
AB  - In this study, we investigated whether recombinant human growth hormone (rhGH)
      influences the progression of myocarditis. We induced experimental autoimmune
      myocarditis in F344 rats by subcutaneous injection of cardiac myosin, and divided
      the rats into three groups: (1) control group, saline injection; (2) pre-treated
      group, subcutaneous injection of rhGH (100 mIU/rat/day for 10 days) before
      induction of experimental autoimmune myocarditis; and (3) post-treated group,
      subcutaneous injection of rhGH (100 mIU/rat/day for 10 days) after induction of
      experimental autoimmune myocarditis. On the 35th day after induction of
      experimental autoimmune myocarditis, all rats were sacrificed and the hearts were
      examined. The increase in body weight was smaller in the control group than the
      pre-treated group and the rate of heart weight/body weight was larger in the
      control group than in the two treated groups. Histopathologically, rats in the
      control group showed multifocal infiltration by inflammatory cells, mainly
      neutrophils, lymphocytes and macrophages, extensive fibrosis, and a higher
      proportion of mast cells in the inflamed region. In contrast, rats in the two
      treated groups showed only minor changes. We found that rhGH did not influence
      the distribution of lymphocytes in peripheral blood in the three groups, and that
      rhGH induced G1 checkpoint dysfunction, thereby arresting the cell cycle in G1
      and inhibiting the proliferation of mast cells in vitro. These findings suggest a
      possible role for mast cells in the progression of myocarditis and the rhGH may
      be a candidate for use as a new tool to treat myocarditis.

PMID- 11245851
TI  - Potentiation by endothelin-1 of vasoconstrictor response in stroke-prone
      spontaneously hypertensive rats.
AB  - Norepinephrine-induced vasoconstriction was significantly greater in perfused
      mesenteric arteries of stroke-prone spontaneously hypertensive rats (SHRSPs)
      compared with cases of age-matched Wistar Kyoto rats (WKYs). Neither endothelin
      ET(A) receptor antagonist FR139317 ((R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1H
      azepinyl)]carbonyl]amino-4-methyl-pentanoyl] amino-3-[3-(1-methyl-1H
      indoyl)]propionyl]amino-3-(2-pyridyl) propionic acid) nor endothelin ET(B)
      receptor antagonist BQ788 [N-cis-2,6-dimethylpiperidinocarbonyl-L-g-methylleucyl
      D-1-methoxycarbonyl-tryptophanyl-D-norleucine] affected the increased responses
      observed in SHRSPs, suggesting that endogenous endothelin-1 is not involved in
      this phenomenon. Norepinephrine-induced vasoconstriction was significantly
      enhanced by subpressor dose of endothelin-1 (0.3 nM), both in SHRSPs and WKYs. In
      SHRSPs, endothelin-1-induced enhancement was abolished by FR139317, in contrast
      to the case with WKYs, in which BQ788 markedly suppressed endothelin-1-induced
      augmentation of norepinephrine responses. Our results indicate that exogenous
      endothelin-1 enhances contractile responses to norepinephrine in mesenteric
      arteries of WKYs and SHRSPs, through activation of different receptor subtypes.

PMID- 11245853
TI  - Effect of a tachykinin NK(2) receptor antagonist, nepadutant, on cardiovascular
      and gastrointestinal function in rats and dogs.
AB  - The effect of the tachykinin NK(2) receptor antagonist, nepadutant (MEN 11420 or
      (c[[(beta-D-GlcNAc)Asn-Asp-Trp-Phe-Dpr-Leu]c(2beta-5beta)])) was assessed on
      cardiovascular function (unanaesthetized rats and anaesthetized dogs) and
      gastrointestinal motor activity (fasted unanaesthetized dogs). The selective
      tachykinin NK(2) receptor agonist, [betaAla(8)]neurokinin A (4-10), up to 100
      nmol/kg, i.v., did not produce changes on mean blood pressure or heart rate in
      unanaesthetized rats. Nepadutant did not affect blood pressure and heart rate up
      to 10 micromol/kg, whereas saredutant (SR 48968 or ((S)-N-methyl-N[4-(4
      acetylamino-4-phenyl piperidino)-2-(3,4-dichlorophenyl)butyl] benzamide), a
      nonpeptide antagonist, produced a transient reduction of mean blood pressure and
      heart rate. Nepadutant up to 20 micromol/kg, i.v. neither caused changes of
      cardiovascular and respiratory parameters in anaesthetized dogs nor induced any
      changes in left ventricular systolic pressure, left ventricular dP/dt or of
      electrocardiogram (lead II) waveforms. Intravenous administration of neurokinin A
      (9 nmol/kg) in unanaesthetized dogs stimulated gastrointestinal motility for 20
      25 min. Nepadutant at 0.1 micromol/kg suppressed the stimulant effects of
      neurokinin A but, up to a dose of 10 micromol/kg, did not produce significant
      changes in the basal migrating motor complexes. We conclude that tachykinin NK(2)
      receptors do not participate in the physiologic regulation of resting
      cardiovascular and respiratory functions and that they do not regulate the fasted
      pattern of gastrointestinal motility. The cardiovascular changes induced by the
      nonpeptide tachykinin NK(2) receptor antagonist, saredutant, likely arise from
      nonspecific effects unrelated to tachykinin NK(2) receptor blockade.

PMID- 11245854
TI  - Role of K+ channels in N-acetylprocainamide-induced relaxation of bovine tracheal
      smooth muscle.
AB  - We examined the relaxant effects of N-acetylprocainamide, the major hepatic
      metabolite of procainamide, on bovine tracheal smooth muscle, focusing on the
      possible involvement of K+ channels. N-acetylprocainamide produced a
      concentration-dependent and full inhibition of the tension development elicited
      by methacholine (0.3 or 1 microM). The potency of N-acetylprocainamide in
      diminishing methacholine-elicited tension development was one-half of that of
      procainamide. By comparison, N-acetylprocainamide inhibited high-K+ (40 mM)
      induced contraction more potently than procainamide though both inhibitions were
      largely reduced when compared to those against methacholine-induced contraction.
      Iberiotoxin (30 nM), Ba(2+) (1 mM) or a combination of both agents significantly
      attenuated the relaxant effect of N-acetylprocainamide on methacholine-induced
      contraction, whereas apamin (100 nM), 4-aminopyridine (300 microM), and
      glibenclamide (10 microM) did not affect it. These results suggest that N
      acetylprocainamide, similar to procainamide, elicits tracheal smooth muscle
      relaxation mainly through the activation of plasma membrane K+ channels.

PMID- 11245855
TI  - The cholesterol absorption inhibitor, ezetimibe, decreases diet-induced
      hypercholesterolemia in monkeys.
AB  - Ezetimibe (1-(4-fluorophenyl)-(3R)-[3-(4-fluorophenyl)-(3S)-hydroxypropyl]-(4S)
      (4-hydroxyphenyl)-2-azetidinone) potently and selectively inhibits the intestinal
      absorption of cholesterol, thereby reducing plasma cholesterol in preclinical
      models of hypercholesterolemia. In rhesus monkeys fed a diet containing 375
      mg/day of cholesterol, 0.1 mg/kg of ezetimibe completely prevented the doubling
      of plasma cholesterol normally induced under these dietary conditions
      (ED(50)=0.0005 mg/kg). Low-density lipoprotein cholesterol (LDL) was dose
      dependently reduced, while high-density lipoprotein cholesterol (HDL) and plasma
      triglyceride were unchanged. A single dose of an ezetimibe analog administered to
      cynomolgus monkeys fed a single cholesterol-containing meal caused a significant
      reduction (-69%) of cholesterol in chylomicrons during the postprandial phase
      without affecting triglyceride content. In rhesus monkeys, apolipoprotein (apo)
      B(48) concentrations in chylomicrons did not differ between control and the
      ezetimibe analog, but apo B(100) was significantly reduced in LDL (-41%). These
      data indicate that these cholesterol absorption inhibitors reduce cholesterol
      content in chylomicrons, which indirectly leads to a decrease in LDL cholesterol
      and particle number.

PMID- 11245856
TI  - GPI 6150, a poly (ADP-ribose) polymerase inhibitor, exhibits an anti-inflammatory
      effect in rat models of inflammation.
AB  - Poly (ADP-ribose) polymerase, a nuclear enzyme activated by DNA strand breaks,
      has been show to play an important role in the pathogenesis of inflammation.
      Here, we investigate the effects of GPI 6150 (1,11b-dihydro-[2H]benzopyrano
      [4,3,2-de]isoquinolin-3-one), a new poly (ADP-ribose) polymerase inhibitor, in
      animal models of acute and chronic inflammation (carrageenan-induced paw edema,
      adjuvant-induced arthritis and zymosan-induced multiple organ failure) where
      oxygen radicals, nitric oxide and peroxynitrite are known to play a crucial role
      in the inflammatory process. The results show that the poly (ADP-ribose)
      polymerase inhibitor GPI 6150 inhibits the inflammatory response (paw swelling,
      and organ injury). The present results demonstrate that inhibition of poly (ADP
      ribose) polymerase by GPI 6150 exerts potent anti-inflammatory effects. Part of
      these anti-inflammatory effects may be related to a reduction of neutrophil
      recruitment into the inflammatory site.

PMID- 11245857
TI  - Inhibition by nifedipine of adherence- and activated macrophage-induced death of
      human gingival fibroblasts.
AB  - The effects of nifedipine on the death and proliferation of gingival fibroblasts
      were investigated to elucidate the mechanism of gingival overgrowth that is
      associated with chronic administration of Ca2+ channel blockers. The number of
      adhered viable and dead fibroblasts obtained from healthy human gingiva increased
      after confluence, whereas cell death was inhibited by nifedipine in a
      concentration-dependent manner. A similar inhibition was also observed in the
      presence of other calcium channel blockers, such as nicardipine, diltiazem, and
      verapamil. When gingival fibroblasts were co-cultured with RAW264 (macrophage
      like) cells, lipopolysaccharide (LPS) caused the concentration-dependent death of
      fibroblasts. Nifedipine significantly inhibited the LPS-induced cell death.
      Although neither LPS nor N-ethyl-2-(1-ethyl-2-hydroxy-2-nitroso-hydrazino)
      ethanamine, a nitric oxide donor, directly caused fibroblast death, 3-morpholino
      sydnonimine (SIN-1), a peroxynitrite donor, induced fibroblast death, regardless
      of the presence of RAW cells. The cell death induced by SIN-1 was not affected by
      nifedipine treatment. LPS stimulation caused an increase in the immunoreactivity
      of inducible nitric oxide synthase (iNOS) and in the nitrite concentration in the
      incubation medium of RAW cells. The induction of iNOS was completely prevented by
      the incubation with nifedipine. The inhibition by nifedipine of nitrite
      production in RAW cells was also observed after treatment with nicardipine, but
      not with either diltiazem or verapamil. Therefore, the inhibition by nifedipine
      of both adherence- and LPS-stimulated macrophage-induced death of fibroblasts may
      be the mechanism of gingival overgrowth seen during chronic treatment with Ca(2+)
      channel blockers.

PMID- 11245858
TI  - Effects of verapamil and elgodipine on isoprenaline-induced metabolic responses
      in rabbits.
AB  - Verapamil (0.17 microg kg(-1) min(-1) intravenous, i.v.) but not elgodipine (35
      ng kg(-1) min(-1)) modestly enhanced the weak blood glucose increase induced by
      the i.v. infusion of isoprenaline (0.3 microg kg(-1) min(-1)) in conscious
      rabbits. However, elgodipine but not verapamil suppressed the increase in
      circulating insulin evoked by the agonist. Both drugs enhanced the rise in plasma
      lactate mediated by isoprenaline but only elgodipine potentiated the lipolytic
      effect of the agonist. In isolated islets elgodipine (10(-6) M) blocked forskolin
      (10(-6) M)-induced insulin release. However, in rabbit adipocytes elgodipine
      potentiated both glycerol release and cAMP accumulation induced by isoprenaline
      (10(-8)-10(-6) M). Excess K(+) (40-60 mM) did not alter basal lipolysis or the
      response to isoprenaline in either rabbit or mouse adipocytes. Therefore, Ca2+
      influx through L-type Ca2+ channels does not seem to play a significant role in
      the lipolytic effect of isoprenaline. Metabolic alterations found with Ca2+
      channel antagonists were of minor intensity and probably devoid of pathological
      implications.

PMID- 11245860
TI  - Cannabinoid CB(1) receptor upregulation in a rat model of chronic neuropathic
      pain.
AB  - Although cannabinoids are known to be more effective analgesics against chronic
      rather than acute pain, the mechanism underlying this phenomenon is still
      unclear. We report now that contralateral thalamic cannabinoid CB(1) receptors
      are upregulated after unilateral axotomy of the tibial branch of the sciatic
      nerve, a rat model of chronic neuropathic pain, and hypothesize that cannabinoid
      CB(1) receptor upregulation contributes to the increased analgesic efficacy of
      cannabinoids in chronic pain conditions.

PMID- 11245859
TI  - Morphine and clonidine activate different K+ channels on rat amygdala neurons.
AB  - In cell-attached patch-clamp recordings from freshly dissociated neurons of the
      rat amygdalohippocampal area, clonidine principally activated a 95-pS
      (picosiemens) inwardly rectifying K+-permeable channel, whereas morphine acting
      at mu-opioid receptors activated a different 130-pS channel. Clonidine's effects
      were largely antagonized by the alpha(2)-adrenoceptor antagonist idazoxan, but
      were poorly mimicked by agmatine. These results partially contradict the
      prevailing hypothesis that alpha(2) and opioid receptors act through the same ion
      channel transduction pathways.

PMID- 11245861
TI  - Research capacity in nursing.

PMID- 11245862
TI  - Using the nursing minimum data set for the Netherlands (NMDSN) to illustrate
      differences in patient populations and variations in nursing activities.
AB  - RATIONALE: A nursing minimum data set (NMDS) provides data that are useful to
      legitimate nurses' contribution to healthcare. In Belgium and the US, such NMDS
      are operational, other countries are developing it, among which is the
      Netherlands. OBJECTIVE: To evaluate whether the nursing minimum data set for the
      Netherlands (NMDSN) is suitable to describe the diversity of patient populations
      and the variability of nursing care. METHODOLOGY: Using the NMDSN data collection
      forms, patient data were collected from 15 different hospital wards. During one
      week, nurses manually completed the NMDSN list for every patient. The data
      analysis methodology from the Belgian MVG was used, including ridit analysis and
      graphs. RESULTS: The NMDSN includes items related to hospital, patient
      demographics, medical condition, nursing process, nursing phenomena, nursing
      interventions, outcomes of nursing care, and complexity of care. There were 686
      individual patients in the study, while for the data analysis their 2090 patient
      days in the hospital were used. Frequencies of nursing phenomena, nursing
      activities and results of care were calculated, transformed into ridit scores,
      and presented graphically as 'fingerprints'. CONCLUSION: The set of NMDSN items
      allows illustrating the diversity of patient populations, and variation in
      nursing care by means of 'fingerprints'.

PMID- 11245863
TI  - A controlled clinical trial of home care management versus hospital care
      management for preterm labour.
AB  - Prenatal hospitalisation has not been shown to reduce perinatal morbidity and
      mortality, yet it is still the treatment of choice for women who experience
      preterm labour. Home care management may be an alternative means of delivering
      safe, efficacious and care for these women. The objectives of this controlled
      clinical trial were to examine differences in neonate's gestational age and
      birthweight, and antenatal stress, social support satisfaction, and family
      functioning among pregnant women receiving home care and those receiving hospital
      care management. Pregnant women experiencing preterm labour (N=250) were randomly
      assigned to home care management (the experimental group [EG]) or hospital care
      management (the control group [CG]). A Perinatal Information Form was used to
      collect data on sociodemographic and pregnancy variables. The High-Risk Pregnancy
      Stress Scale, Brown's Social Behaviors Inventory, and the Family Assessment
      Measure III Dyadic Relationships Scale were administered to the women at
      randomisation (T1) and at 1-week (T2) and 2-weeks (T3) after randomisation.
      Gestational age and birthweight were similar in the two groups of neonates. Women
      in the EG reported that antenatal stress was significantly lower at T3 than at T1
      and T2, while for those in the CG, antenatal stress was significantly lower at T3
      than at T1, and significantly lower at T2 than at T1. Women in the EG were more
      satisfied with support from the male partner at T3 than women in the CG. There
      was no significant difference between the two groups in family functioning at T1,
      T2 and T3. These findings indicate that home care management is a safe and
      efficacious mode of health care delivery for women experiencing preterm labour.

PMID- 11245865
TI  - Student nurses' experiences of caring for patients in pain.
AB  - Poor pain assessment contributes to inadequate pain relief. Studies in the United
      States have shown that while student nurses become more sensitive to
      psychological distress during training, they become less sensitive to pain.
      However, a recent study by the authors in the United Kingdom found that while
      inferences of psychological distress increased there was no change in inferences
      of pain over the common foundation programme. This study set out to explore their
      experiences of caring for patients in pain during the first 18 months of their
      training in order to understand how these experiences might affect their
      sensitivity to patient's pain. Interviews with 15 students following their common
      foundation programme showed that they experienced a wide range of strong emotions
      when caring for patients in pain. Their relatively junior status in the wards
      seemed to place them in difficult positions and provided them with little
      support. Theories of desensitisation, cognitive dissonance and acculturation have
      been proposed to explain decreasing sensitivity to pain. The lack of a
      significant change in students' inferences of pain and the analysis of their
      interviews suggest that their experiences are more varied than these theories
      suggest. The students experiences echo those found in previous studies relating
      to the socialisation of student nurses and emotional labour (Melia, 1987.
      Learning and Working. The Occupational Socialization Nurses. Tavistock
      Publishers, London; Smith, 1992. The Emotional Labour of Nursing. Macmillan,
      London). These findings have important implications for both nurse education and
      the mechanisms to support student nurses in clinical practice.

PMID- 11245864
TI  - Actions seen as demanding in patients with severe dementia during one year of
      intervention. Comparison with controls.
AB  - Behaviours, viewed by nurses as demanding, performed by patients with severe
      dementia were investigated during one year of intervention. Supervised
      implementation of individually planned care and systematic clinical supervision
      were implemented on one experimental ward (EW) while another ward (CW) served as
      control. Each ward had 11 patients. At baseline and after 6 and 12 months of
      intervention structured interviews with the patients' assigned nurses were
      conducted based on the Demanding Behaviour Assessment Scale and Multi Dimensional
      Dementia Assessment Scale. At the EW there was a decreased frequency (p=0.000)
      and a reduced occurrence of physical behaviours (p=0.008), a decreased frequency
      (p=0.029) and a reduced occurrence of vocal behaviours (p=0.002). No significant
      changes were seen at the CW. Bearing the small sample size in mind, the findings
      indicate that individually planned care and systematic clinical supervision could
      be a means of reducing the frequency, and/or effect the nurses' attitude and
      interpretation of the patients' behaviour as demanding. The findings, however,
      can only be seen as indications for further research, but point to the importance
      of including effect variables related to patients when intervening in nursing
      care.

PMID- 11245866
TI  - Risk factors of child maltreatment within the family: towards a knowledgeable
      base of family nursing.
AB  - The purpose of this study was to compare family dynamics in child maltreating
      families (n=42) with that in ordinary families with children (n=77), and to
      ascertain risk factors of child maltreatment within the family. Child
      maltreatment was defined as physical, psychological or sexual abuse or neglect of
      a child by a parent. Data were collected using questionnaires (Family Dynamics
      Measure 2, FMD 2) (N=119) basing on Barnhill's conceptual framework of healthy
      family systems and analysed by forming sum variables and logistic regression. The
      study results indicate that family functioning in child maltreating families is
      lower on all dimensions of family dynamics (individuation, mutuality,
      flexibility, stability, communication and roles) than that in ordinary families
      with children. Furthermore, it seems that specific risk factors, detected with
      logistic regression analysis, are related to whether child maltreatment occurs in
      the family or not. These include the parent's low educational background, many
      children in the family, unemployment of a parent, low individuation of the family
      members, and poor stability and security within the family. The results of this
      study provide guidelines for detecting and preventing child maltreatment as well
      as for recognising its existence, although no generalizations can be made due to
      the small sample size and complexity of the phenomenon under study.

PMID- 11245867
TI  - Recognising pain in older adults living in sheltered accommodation: the views of
      nurses and older adults.
AB  - Sixty-six randomly selected older adults and their contact nurses participated in
      interviews based on standardised assessments of pain and open-ended questions
      focusing how pain was expressed and recognised. The sample included older adults
      with normal as well as cognitively impaired function. Seventy-nine percent of
      older adults with normal cognition were often in pain. Contact nurses assessed
      pain in 57% of cognitively impaired older adults. The content in the statements
      showed that pain recognition was a communicative interactive process based on
      verbal and non-verbal expressions. The process comprised attempts to understand
      the cause and intention of the expression and to verify the presence of pain.
      Changes in mood, facial expressions and physiological responses were described
      less often by older adults than by their nurses. Contact nurses of cognitively
      impaired older adults judged immobility as the source of pain, that it was
      possible to see when the person was in pain and that pain was expressed by
      paralinguistic and body language more often than contact nurses of cognitively
      healthy older adults. Characteristics of nurses and older adults could facilitate
      or hinder pain recognition. The findings indicate a need for reflective
      discussions in the staff group focusing on how to perform systematic assessments
      of verbal and non-verbal expressions and of hindrances and facilitators for
      recognising pain in older adults.

PMID- 11245868
TI  - Measuring stroke patients' health status in the early post-stroke phase using the
      SF36.
AB  - This paper aims to explore the self-perceived health status of stroke patients,
      the factors that contribute to the perception and the relevance of the findings
      to researchers and practitioners. Outcomes were measured at one, three and six
      months post-stroke for 153 stroke patients and pre-morbid characteristics were
      gathered from GPs. Health status was measured using the Short Form 36 (SF36).
      Stroke patients' health status was significantly worse than a general population
      for four health dimensions (physical functioning, role physical, vitality and
      social functioning). Regression analyses with the SF36 profile scores as
      dependent variables revealed one model where associations between independent and
      dependent variables were relatively strong (physical functioning), the remaining
      seven models yielded weak associations. Self-perceived health status was not
      strongly related to impairment, disability or cognitive function. There are
      implications for researchers and practitioners across a range of professions.
      Researchers should aim to identify factors that explain stroke patients'
      perception of their own health and the impact of their perception on
      rehabilitation. Practitioners should consider the possible effects of low
      vitality on treatment concordance.

PMID- 11245869
TI  - Postoperative pain: a comparison of adolescent inpatient and day patient
      experiences.
AB  - This three-year study investigated the experience of postoperative pain and its
      management following elective surgery in an adolescent population aged 12-18
      years (n=351) in 5 NHS trusts. In addition to the adolescents, one parent of each
      adolescent and a range of health professionals including surgeons, anaesthetists
      and registered nurses were interviewed concerning their views on acute pain in
      adolescent patients. The results presented in this paper are those related to the
      management of day and inpatient surgery in this adolescent population. Data were
      collected pre-operatively and postoperatively (days 1 and 3) using semi
      structured interviews, telephone interviews, self-completion questionnaires and
      standardised tools to measure pain intensity (Adolescent Pediatric Pain Tool),
      psychological adjustment to adolescence (Offer Self-Image Questionnaire-Revised)
      and emotional state (Hospital Anxiety and Depression Scale). Day cases were
      discharged on the day of surgery while most inpatients were discharged on the
      first postoperative day.

PMID- 11245870
TI  - Stress, loneliness, and depression in Taiwanese rural community-dwelling elders.
AB  - This study examined the stressors and stress levels, loneliness, and depression
      experienced by Taiwanese rural elders and determine if differences in the level
      of stress were associated with specific person-environmental characteristics. The
      relationship between stress and depression was also explored. A total of 201
      older rural community residents participated in the study. Findings showed that
      rural elders experienced a number of stressors related to health and family
      issues. Differences in the degree of stressfulness of individuals differed by
      gender, educational level, living arrangement, and socioeconomic status (SES).
      Findings in this study also showed that there was a high association among stress
      level, depressive symptoms, and mood status. The findings of this study will
      assist community health policy-makers in determining the need for health-related
      services for rural elders experiencing these problems.

PMID- 11245871
TI  - Autonomy: an important component for nurses' job satisfaction.
AB  - This quantitative pilot study (n=178), conducted in a large Brisbane teaching
      hospital in Australia, found autonomy to be the most important job component for
      registered nurses' job satisfaction. The actual level of satisfaction with
      autonomy was 4.6, on a scale of 1 for very dissatisfied to 7 for very satisfied.
      The mean for job satisfaction was 4.3, with the job components professional
      status and interaction adding most substantially to the result. There was
      discontentment with the other two job components, which were task requirements
      and organisational policies. Demographic comparisons showed that nurses who were
      preceptors had significantly less job satisfaction than the other nurses at the
      hospital.

PMID- 11245873
TI  - Scales of mussel bed complexity: structure, associated biota and recruitment.
AB  - Hierarchically scaled surveys were carried out on beds of the brown mussel Perna
      perna (Linnaeus) on the South coast of South Africa. The object was to assess
      spatial and temporal variations in the complexity of mussel beds and to
      investigate relationships between mussel bed complexity and mussel recruitment.
      Complexity was divided into three components: physical complexity; demographic
      complexity; associated biota. A series of variables within each component were
      recorded at two different scales (10 and 50 cm) within nested quadrats on three
      separate occasions. The nested ANOVA design explicitly incorporated spatial scale
      as levels of the ANOVA. These scales were: shores (areas 1 km in length separated
      by 25 km); transects (areas 20 m in length separated by 100s of meters); 50x50-cm
      quadrats separated by meters and 10x10-cm quadrats separated by cm) This approach
      was intended to generate hypotheses concerning direct associations between
      recruitment and complexity versus co-variation due external processes. Three main
      questions were addressed: (1) At what scale does each variable of complexity
      exhibit greatest significant variation? (2) At these scales is there similar
      ranking of variables of complexity and recruitment? (3) Within this/these scales,
      is there any significant relationship between the variables measured and mussel
      recruitment? On two occasions (Nov. 97 and Mar. 98) the majority of variables
      showed greatest significant variation at the transect-scale. On a third occasion
      (Oct. 97) most variables showed greatest significant variation at the quadrat
      scale and the site-scale. On all occasions a markedly high percentage of the
      variation encountered also occurred at the smallest scale of the study, i.e., the
      residual scale of the ANOVA analyses. Some similarity in the ranking of variables
      occurred at the transect scale. Within the transect-scale, there was little
      indication of any relationship between variables of complexity and recruitment.
      Relationships were inconsistent either among transects or among sampling
      occasions. Overall, the results suggest that a high degree of variation in mussel
      bed complexity consistently occurs at very small scales. High components of
      variance generally also occur at one or more larger scales; however, these scales
      vary with season. Mussel recruitment does not appear to be directly affected by
      complexity of mussel beds. Instead it appears external factors may influence both
      complexity and recruitment independently. In addition recruitment may influence
      complexity rather than vice versa.

PMID- 11245872
TI  - Treatment type and symptom severity among oncology patients by self-report.
AB  - Oncology patients receiving chemotherapy (n=109) and radiation therapy RT (n=161)
      reported symptom concerns and severity on the 25-item therapy-related symptom
      checklist (TRSC). Secondary analysis of the self-reports of the two treatment
      groups was done using the Mann-Whitney U Test. Thirteen symptoms differed
      significantly between the two groups. RT patients reported significantly greater
      severity of five symptoms (p<0.05) during therapy. Chemotherapy patients reported
      significantly greater severity of eight different symptoms. The other 14 items
      showed a heterogeneous pattern of self-reported patient symptom concerns. The
      TRSC appears to be a clinically useful self-report checklist that captures the
      more important symptom concerns of both RT and chemotherapy patients. Earlier
      efforts to develop this checklist are reviewed briefly.

PMID- 11245874
TI  - Photo-acclimation of the hermatypic coral Stylophora pistillata while subjected
      to either starvation or food provisioning.
AB  - This study investigated the photo-acclimation capacity of the coral Stylophora
      pistillata (Esper). Outer branches of coral colonies, taken from 2 m, were
      subjected to 90, 20, or 3% of incident surface photosynthetic active radiation
      (PAR(0)), or kept in total darkness. The corals were maintained either in
      filtered seawater (i.e., under starvation), or in seawater that had daily
      additions of zooplankton (rotifers). The experiments were maintained for 31 days.
      Zooxanthellae population densities and chlorophyll concentrations increased in S.
      pistillata fragments subjected to 20 and 3% PAR(0). The zooxanthellae densities
      decreased after 6 days in corals kept in total darkness, although chlorophyll
      concentrations remained higher. Corals that were fed and subjected to 90% PAR(0)
      showed lower degrading zooxanthellae frequencies, higher photosynthetic and
      respiration rates, and higher chlorophyll concentrations than corals in the same
      light regime under starvation. Complete acclimation to dim (20% PAR(0)) and low
      (3% PAR(0)) light was only apparent for corals fed with zooplankton. Changes in
      zooxanthellae population densities occurred through differential rates of
      zooxanthellae division and degradation.

PMID- 11245875
TI  - Factors influencing planktonic, post-settlement dispersal of early juvenile blue
      crabs (Callinectes sapidus Rathbun).
AB  - An emerging body of literature points to post-settlement, planktonic dispersal as
      a key determinant of distribution and abundance patterns of aquatic organisms,
      yet little is known about mechanisms inducing such dispersal. Recent evidence
      suggests that early juvenile blue crabs (Callinectes sapidus Rathbun) may use
      planktonic emigration as a means of post-settlement dispersal. The goal of this
      study was to identify mechanisms inducing post-settlement, planktonic dispersal
      of early juvenile blue crabs. A combination of field mark-recapture experiments
      in large seagrass beds within a 2x3 km region near Oregon Inlet, North Carolina,
      USA, and a series of laboratory flume experiments examined the effects of day vs.
      night, crab size (first-second juvenile benthic instars: J1-J2 vs. third-fifth
      juvenile benthic instars: J3-J5), crab density and current speed on planktonic
      dispersal of early juvenile blue crabs. Transport of dead crabs in the flume
      experiment identified that planktonic dispersal was an active behavioral response
      rather than a passive response to increasing current speed. The experimental
      results demonstrated that planktonic dispersal can range from 4 to 18% under
      medium to high flow conditions. Planktonic dispersal of juvenile crabs is (1) an
      active behavioral response, (2) increased significantly with current speeds above
      20 cms(-1), and (3) was higher for relatively large (J3-J5) than small (J1-J2)
      instars. There was a non-significant trend towards greater dispersal at night
      than during the day in the field experiment, and no effect of crab density on
      dispersal in the flume experiment. The results from this study highlight the need
      to consider mechanisms inducing post-settlement, planktonic dispersal when
      attempting to understand and predict recruitment and population dynamics of
      aquatic organisms, as well as when linking hydrodynamics, animal behavior and
      planktonic dispersal.

PMID- 11245876
TI  - Effects of herbivorous snails and macroalgal canopy on recruitment and early
      survivorship of the barnacle Semibalanus balanoides (L.).
AB  - This study investigated the effects of grazing by the herbivorous snail Littorina
      littorea (L.) and the presence of a macroalgal canopy on recruitment and early
      survivorship of the barnacle Semibalanus balanoides (L.) at four sites of various
      distances from the mouth of Toothacher Cove on Swans Island in the Gulf of Maine
      in 1998. Recruitment plates were attached to the substrate at each site in all
      possible treatment combinations, including either presence of absence of
      macroalgal canopy, presence or absence of the herbivore, and presence or absence
      of a cage. Significant differences in recruitment were observed among sites in
      April and May, but not in June. The average number of recruits also varied
      significantly among herbivore treatments in May and June, and in the May
      macroalgaexherbivore interaction. Survivorship did not differ among sites, but
      did vary significantly among herbivore treatments. These differences were due
      almost entirely to consistently low recruitment and survival in the uncaged or
      open controls. Comparisons of the caged and open treatments explained between 88
      and 99% of the variation in the respective main effects tests. The presence or
      absence of L. littorea or of macroalgal canopy had little effect on S. balanoides
      recruitment or survivorship. Results support previous conclusions that
      recruitment is greater on more exposed shores and suggest that exclusion cages
      may protect barnacle recruits from factors such as desiccation and the whiplash
      effect of macroalgal fronds.

PMID- 11245877
TI  - Validation of daily otolith increments in glass-phase American eels Anguilla
      rostrata (Lesueur) during estuarine residency.
AB  - Prior to making inferences from otoliths about the residence time and growth rate
      of glass-phase anguillid eels Anguilla in estuaries, it is necessary to validate
      the deposition rate of microincrements in the otoliths. Glass-phase American eels
      Anguilla rostrata (Lesueur), which had been captured near the mouth of an estuary
      in Maine, USA, prior to freshwater exposure, deposited increments at a daily rate
      at ambient temperature and salinity in a field and laboratory study. The
      regression for glass eels not possessing a transition ring was: I=0.976(D
      1)+0.434, where I is the number of otolith increments distal to a fluorescent
      mark placed on the otolith at the beginning of the experiment, and D is the
      number of days in the experiment, which ranged from 7 to 49. The slope was not
      significantly different than 1. Unexpectedly, many glass eels deposited the
      transition ring during the experiment, although this ring had previously been
      thought to mark entry into fresh water. The regression for these glass eels was:
      I=0.961(D-1)-3.880, and the slope was not significantly different than 1. The
      negative intercept suggests that approximately 4 days were lost from the otolith
      record during deposition of the ring. This study demonstrated daily deposition of
      increments prior to freshwater exposure and demonstrated that deposition of the
      transition ring is not linked to freshwater entry.

PMID- 11245878
TI  - Why do juvenile fish utilise mangrove habitats?
AB  - Three hypotheses to discern the strong positive association between juvenile fish
      and mangrove habitat were tested with field and laboratory experiments.
      Artificial mangrove structure in the field attracted slightly more juvenile fish
      than areas without structure. Artificial structure left to accumulate fouling
      algae attracted four-times the total number of juvenile fish than areas without
      structure or areas with clean structure. Community composition of fish attracted
      to structure with fouling algae was different when compared with areas with no
      structure or clean structure; five species were attracted by structure with
      fouling algae whilst two species were associated with structure regardless of
      fouling algae. Algae were linked to increased food availability and it is
      suggested that this is an important selection criteria for some species. Other
      species were apparently attracted to structure for different reasons, and
      provision of shelter appears to be important. Predation pressure influenced
      habitat choice in small juvenile fish in laboratory experiments. In the absence
      of predators, small juveniles of four out of five species avoided shelter but
      when predators were introduced all species actively sought shelter. Large fish
      were apparently less vulnerable to predators and did not seek shelter when
      predators were added to their tank. Feeding rate was increased in the mangrove
      habitat for small and medium-sized fish compared with seagrass beds and mudflats
      indicating increased food availability or foraging efficiency within this
      habitat. Larger fish fed more effectively on the mudflats with an increased
      feeding rate in this habitat compared with adjacent habitats. The most important
      aspect of the mangrove habitat for small juvenile fish is the complex structure
      that provides maximum food availability and minimises the incidence of predation.
      As fish grow a shift in habitat from mangroves to mudflat is a response to
      changes in diet, foraging efficiency and vulnerability to predators.

PMID- 11245879
TI  - Effects of 4-n-nonylphenol and 17beta-oestradiol on early development of the
      barnacle Elminius modestus.
AB  - Pollutants that are present in the aquatic environment and cause abnormal
      endocrine function in wildlife populations have been termed endocrine disrupting
      chemicals (EDCs). The impacts of these chemicals on the reproduction and
      development of vertebrates has been shown to be significant in both field studies
      and laboratory experiments. Over the past decade the number of investigations
      into the impacts of EDCs that affect reproductive and sexual characteristics
      (reproductive EDCs) has increased and evidence of their potency is evident in
      numerous wildlife species and through data from in vitro tests. However, little
      information is available on whether chemicals which act as EDCs in vertebrate
      species affect aquatic invertebrates. The case of imposex in archeogastropods
      following exposure to tributyltin (TBT) is a notable exception. Moreover, a
      number of studies have shown that development, fecundity and reproductive output
      of some aquatic invertebrates are affected significantly by exposure to
      pollutants. In order to determine whether external signs of exposure to
      vertebrate EDCs can be observed and monitored in invertebrate species, we exposed
      larvae of the barnacle Elminius modestus to environmentally realistic
      concentrations of the xeno-oestrogen, 4-n-nonylphenol (NP), and the natural
      oestrogen, 17beta-oestradiol (E(2)). Early life stages (nauplii and cyprids) were
      also exposed in the laboratory to determine whether there were effects on the
      timing of larval development and settlement. Ovary development and size of
      juveniles was measured following chronic exposure. Exposure to NP in the
      concentration range 0.01-10 ug l(-1) resulted in disruption of the timing of
      larval development. Similar results were obtained with E(2). Pulse exposures
      showed that the timing of exposure is critical and exposures for a period of 12
      months caused long-term effects. A linear, concentration-dependent response was
      not evident.

PMID- 11245880
TI  - Effects of toxic and non-toxic cyanobacteria on grazing, zooplanktivory and
      survival of the mysid shrimp Mysis mixta.
AB  - We measured the effect of toxic and non-toxic cyanobacteria strains on grazing,
      predation rates and survival of the mysid shrimp Mysis mixta by means of
      laboratory experiments. Juvenile and adult M. mixta fed most actively on the non
      toxic strains Aphanizomenon flos-aquae and Nodularia sphaerocarpa as on high
      quality food, the green flagellate Brachiomonas submarina, whereas grazing on the
      toxic N. spumigena was significantly lower than on the other strains. The mysids
      showed normal functional responses; decreasing clearance rates at increasing
      concentrations of cyanobacteria. In a separate predation experiment, the feeding
      rates on copepods declined in the presence of aggregated non-toxic cyanobacteria.
      However, we could not demonstrate increased mortality in a 7-week experiment
      where mysids were exposed to high concentrations of toxic N. spumigena

PMID- 11245881
TI  - Feeding characteristics of two tintinnid ciliate species on phytoplankton
      including harmful species: effects of prey size on ingestion rates and
      selectivity.
AB  - The feeding abilities of two tintinnid ciliates, Favella ehrenbergii and Favella
      taraikaensis, on 10 species of flagellates including harmful marine algae were
      examined under single prey conditions, and selective feeding of F. taraikaensis
      on two species of algae of different sizes was investigated under mixed prey
      conditions. Ingestion rates calculated from the rate of increases of auto
      fluorescent particles inside food vacuoles in individuals ranged from 0.5 to 22.1
      cells ind(-1) h(-1) for F. ehrenbergii and from 0.8 to 44.9 cells ind(-1) h(-1)
      for F. taraikaensis on nine species of prey algae. Significant ingestion rates of
      both Favella species could not be detected on Heterosigma akashiwo, although some
      individuals of both species were observed ingesting H. akashiwo in the initial
      incubation period. The relationship between prey cell volume and ingestion rate
      could be expressed mathematically for both Favella species, indicating that it is
      possible to estimate the potential feeding activity of each Favella species on
      specific algae using an equation, and may be applicable to evaluate the food
      value of prey alga for both Favella species. When F. taraikensis was fed mixtures
      of H. circularisquama and Pavlova lutheri, significant ingestion rates of H.
      circularisquama by F. taraikaensis could not be measured when H. circularisquama
      accounted for less than 20% of the other prey biomass. However, clear selectivity
      for H. circularisquama was observed when H. circularisquama reached and exceeded
      34% of the other prey biomass. Under mixed prey conditions, it is likely that the
      selectivity of F. taraikaensis is stronger for larger prey compared to prey algae
      with a size near the lower limit on which F. taraikaensis can feed.

PMID- 11245882
TI  - Size-related shifts in the habitat associations of young-of-the-year winter
      flounder (Pseudopleuronectes americanus): field observations and laboratory
      experiments with sediments and prey.
AB  - Field surveys and laboratory studies were used to determine the role of substrata
      in habitat selection by young-of-the year winter flounder. A synoptic field
      survey of winter flounder and sediments in the Navesink River-Sandy Hook Bay
      estuarine system in New Jersey demonstrated that winter flounder distribution was
      related to sediment grain size. Analysis using a generalized additive model
      indicated that the probability of capturing 10-49 mm SL winter flounder was high
      on sediments with a mean grain diameter of </=0.5 mm, while fish 50-95 mm were
      least likely to be collected on fine sediments and most commonly on sediments
      with a grain-size near 1.0 mm. In the laboratory, sediment preferences and the
      burying ability of winter flounder (15-69 mm SL) were tested by exposing fish in
      10-mm size groups to a choice of azoic sediments of different sediment grain
      sizes. Smaller individuals (<40 mm SL) preferred fine-grained sediments while
      larger individuals (>/=40 mm SL) preferred coarse-grained sediments. Burying
      ability increased with size and all flounders avoided sediments that prevented
      burial. Subsequent laboratory experiments revealed that the presence of live prey
      (Mya arenaria) can over-ride sediment choice by winter flounder (50-68 mm SL)
      indicating the complexity of interrelated factors in habitat choice.

PMID- 11245883
TI  - The placebo effect and relaxation response: neural processes and their coupling
      to constitutive nitric oxide.
AB  - The placebo effect appears to be a real phenomenon as is the scientifically
      demonstrated and examined relaxation response. Given this, we attempt to
      understand how these phenomena work in light of our current understanding of
      central and peripheral nervous system mechanisms. Central to our hypothesis is
      the significance of norepinephrine, nitric oxide and opioid signaling both in the
      central and peripheral nervous system. In this regard, we find that nitric oxide
      controls norepinephrine processes on many levels, including synthesis, release
      and actions. In closing, we conclude that enough scientific information exists to
      support these phenomena as actual physical processes that can be harnessed to
      provide better patient care.

PMID- 11245884
TI  - Receptor systems mediating c-fos expression within trigeminal nucleus caudalis in
      animal models of migraine.
AB  - In intracranial structures unmyelinated C- and Adelta-fibers of the trigeminal
      nerve transmit pain stimuli from meninges to the trigeminal nucleus caudalis
      (Sp5C). Peripheral nerve endings surround meningeal vessels (the so-called
      trigeminovascular system) and contain vasoactive neuropeptides (calcitonin gene
      related peptide, substance P and neurokinin A). Activation of the
      trigeminovascular system promotes a meningeal sterile inflammatory response
      through the release of neuropeptides by peripheral endings. Orthodromic
      conduction along trigeminovascular fibers transmits information centrally with
      induction of immediate early c-fos gene within post-synaptic Sp5C neurons, as a
      marker of neuronal activity within central nociceptive pathways. In laboratory
      animals the system is activated by either electrical stimulation of the TG,
      chemical stimulation of the meninges, electrical or mechanical stimulation of the
      superior sagittal sinus or by induction of cortical spreading depression. All
      these techniques induce c-fos within Sp5C and are used as a rodent/feline model
      of vascular headache in humans. Up-to-date there is evidence that at least ten
      receptors (5-HT(1B), 5-HT(1D), 5-HT(lF), 5-HT(2B), NK-1, GABA(A), NMDA, AMPA,
      class III metabotropic glutamate receptors, and opioids mu receptors) modulate c
      fos expression within Sp5C. These receptors represent potential targets for anti
      migraine drugs as shown by triptans (5-HT(1B/1D/1F)) and ergot alkaloids (5
      HT(1A1B/1D/1F)). This review discusses the importance of c-fos expression within
      Sp5C as a marker of cephalic nociception, the different cephalic pain models that
      induce c-fos within Sp5C, the receptors involved and their potential role as
      targets for anti-migraine drugs.

PMID- 11245885
TI  - Emerging roles for semaphorins in neural regeneration.
AB  - Progressive axon outgrowth during neural development contrasts with the failure
      of regenerative neurite growth in the mature mammalian central nervous system
      (CNS). During neuroembryogenesis, spatiotemporal patterns of repellent and
      attractant activities in the vicinity of the growth cone favor neurite outgrowth.
      In the mature CNS, however, a relative balance between forces supporting and
      restricting axon growth has been established, only allowing subtle morphological
      changes in existing neuritic arbors and synapses. Following CNS injury, this
      balance shifts towards enhanced expression of growth-inhibiting molecules and
      diminished availability of their growth-promoting counterparts. Evidence is now
      emerging that the proteins governing developmental axon guidance critically
      contribute to the failure of injured central neurons to regenerate. As a first
      step toward elucidation of the role of chemorepulsive axon guidance signals in
      axonal regeneration, the effects of lesions of the central and peripheral nervous
      system on the expression of Semaphorin3A, the prototype and founding member of
      the semaphorin family of axon guidance signals, and of the Semaphorin3A receptor
      proteins neuropilin-1 and plexin-A1 have recently been examined. Here we review
      the first evidence indicating that (i) lesion-induced changes in the expression
      of chemorepulsive semaphorins relate to the success or failure of injured neurons
      to regenerate and (ii) semaphorins may represent important molecular signals
      controlling multiple aspects of the cellular response that follows CNS injury. In
      the future, genetic manipulation of the injury-induced changes in the
      availability of semaphorins and/or of their receptors will provide further
      insight into the mechanisms by which semaphorins influence neural regeneration.

PMID- 11245886
TI  - Microglia and the pathogenesis of spongiform encephalopathies.
AB  - Alterations in the phenotype and function of microglia, the resident mononuclear
      phagocytes of the central nervous system, are among the earliest indications of
      pathology within the brain and spinal cord. The prion diseases, also known as
      spongiform encephalopathies, are fatal neurodegenerative disorders with sporadic,
      genetic or acquired infectious manifestations. A hallmark of all prion diseases
      is the aberrant metabolism and resulting accumulation of the prion protein.
      Conversion of the normal cellular protein [PrP(c)] into the abnormal pathogenic
      (or disease-causing) isoform [PrP(Sc)] involves a conformational alteration
      whereby the alpha-helical content is transformed into beta-sheet. The
      histological characteristics of these disorders are spongiform change,
      astrocytosis, neuronal loss and progressive accumulation of the protease
      resistant prion isoform. An additional upregulation in microglial response has
      been reported in Kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler
      Scheinker syndrome (GSS), scrapie, in transgenic murine models and in culture,
      where microglial activation often accompanies prion protein deposition and
      neuronal loss. This article will review the roles of microglia in spongiform
      encephalopathies.

PMID- 11245887
TI  - Say NO to Alzheimer's disease: the putative links between nitric oxide and
      dementia of the Alzheimer's type.
AB  - Alzheimer's disease (AD) is the most common form of dementia, with progressive
      cognitive deficits being the primary symptom. AD is neuropathologically
      characterized by amyloid and neurofibrillary tangle depositions, basal forebrain
      cholinergic deficit, and extensive neuronal loss and synaptic changes in the
      cortex and hippocampus. Mutations of amyloid precursor protein or presenilin
      genes or apolipoprotein E gene polymorphism appear to affect amyloid formation,
      which in turn causes neuronal death via a number of possible mechanisms,
      including Ca(2+) homeostasis disruption, oxidative stress, excitotoxicity, energy
      depletion, neuro-inflammation and apoptosis. Nitric oxide (NO) is an enzymatic
      product of nitric oxide synthase, which exists in three isoforms. In addition to
      its vasoactive and immunological properties, NO has significant
      neurophysiological functions. However, NO can also be neurotoxic primarily due to
      its free radical properties, and it has been implicated in neurodegenerative
      diseases. Interestingly, there is increasing evidence that NO may have a role in
      the aforementioned AD pathogenetic mechanisms, and putative links between NO and
      AD are beginning to be recognized. This review focuses on these issues
      highlighting the possible relevance of NO in AD, either as a neuroprotective or
      neurotoxic agent.

PMID- 11245888
TI  - In situ zymography: topographical considerations.
AB  - In situ gelatin zymography is a simple technique providing valuable information
      about the cellular and tissue localization of gelatinases. Until recently, the
      use of this technique has been confined to soft, relatively homogeneous tissue.
      In this report in situ zymography has been utilized to assess the sub-lamellar
      location of gelatinases in the hard, semi-keratinized epidermal layer and the
      adjacent soft connective tissue matrix of the dermis of the equine hoof. We show
      that alterations in the orientation at which the tissue is dipped and withdrawn
      from the emulsion cause profound alterations in emulsion thickness. Microscopic
      variations in the surface topography of frozen tissue sections also influence
      emulsion thickness making interpretation of the results difficult. Given these
      results, researchers must be aware of potential variations in zymographic
      analysis may be influenced by physical tissue parameters in addition to suspected
      gelatinase activity.

PMID- 11245889
TI  - Screening of the Bacillus thuringiensis Cry1Ac delta-endotoxin on the artificial
      phospholipid monolayer incorporated with brush border membrane vesicles of
      Plutella xylostella by optical biosensor technology.
AB  - The binding of Cry1Ac, an insecticidal protein of Bacillus thuringiensis, to a
      brush border membrane (BBM) isolated from midguts of the diamondback moth
      Plutella xylostella was examined by surface plasmon resonance (SPR)-based
      biosensor. BBM was mixed with 1,3-ditetradecylglycero-2-phosphocholine (PC14), a
      neutral charged artificial lipid, and was reconstructed to a monolayer on a
      hydrophobic chip for the biosensor. The binding of Cry1Ac to the reconstructed
      monolayer was analyzed by a two-state binding model, and it was shown that Cry1Ac
      bound to the monolayer in the first step with an affinity constant (K(1)) of 508
      nM, followed by the second uni-molecular step with an equilibrium constant (K(2))
      of 0.472. The overall affinity constant K(d) was determined to be 240 nM. The
      binding was markedly inhibited by N-acetyl-D-galactosamine (K(i)=8 mM). The
      monolayer was shown to retain a high affinity to Cry1Ac, providing an insect-free
      system for rapid and large-scale screening of B. thuringiensis insecticidal
      proteins by the SPR-based biosensor technology.

PMID- 11245890
TI  - Dansylation of hydroxyl and carboxylic acid functional groups.
AB  - Fluorescent labeling of primary and secondary amines using dansyl chloride has
      been widely used in the past. Its application provides an extremely sensitive
      means to detect amine functional groups to amounts of less than 1 microg of
      material. This work describes a method for the dansylation of hydroxyl (-OH) and
      carboxylic acid (-COOH) functional groups. This technique is demonstrated with
      ethanol, gamma hydroxy butyric acid (GHB), benzoic acid, and p-chloroaniline.
      Sensitivity of detection for all compounds are microgram or microliter. For the
      compounds ethanol and GHB which are liquids at room temperature, as little as 1
      microl quantity can be detected. Benzoic acid and p-chloroaniline which are
      solids at room temperature can be detected at levels of 1 microg. Fast thin layer
      chromatography was accomplished using acetone as the resolving solvent, which
      resulted in good differentiation of analytes for R(f) measurement. The
      dansylation reaction performed similarly at pH 11, 10 and 9.6 and uses 2 molar
      Na(2)CO(3).

PMID- 11245891
TI  - Protein concentration of cerebrospinal fluid by precipitation with Pyrogallol Red
      prior to sodium dodecyl sulphate-polyacrylamide gel electrophoresis.
AB  - The Pyrogallol Red Molybdate (PRM) and Coomassie Brilliant Blue (CBB) protein dye
      binding assays have been applied to samples of cerebrospinal fluid (CSF) to
      investigate protein concentration by dye precipitation prior to sodium dodecyl
      sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The protein concentration
      values of the CSF samples (N=62) showed good agreement between the PRM and CBB
      assays as indicated by linear regression analysis (y(PRM)=1.033x(CBB)+1.004 in
      units of mg/l, r=0.99) but the PRM assay was optimal for protein concentration as
      the PRM protein-dye complex was less soluble allowing protein recovery over a
      wider working range. Dye precipitation using PRM is recommended as a simple,
      rapid and economic method for protein concentration of samples of CSF prior to
      SDS-PAGE.

PMID- 11245892
TI  - A piezoelectric quartz crystal impedance study on Cu(2+)-induced precipitation of
      bovine serum albumin in aqueous solution.
AB  - Piezoelectric quartz crystal impedance (QCI) technique was used for monitoring
      the Cu(2+)-induced precipitation of bovine serum albumin onto the gold electrode.
      The critical precipitate concentration of Cu(2+) reflected by the significant
      decrease in the resonant frequency was estimated to be 9.98 x 10(-5) mol x l(-1),
      and the saturated adherence of the precipitate on the electrode occurred when the
      Cu(2+) concentration was greater than 9.79x10(-3) mol x l(-1). The frequency
      shift in air was about 85.5% of that in liquid, and the Deltaf(0)/DeltaR(1) ratio
      found in solution was 82.67 Hz Omega(-1), suggesting that the frequency response
      was predominated by the mass change due to precipitate adherence to the electrode
      surface. The response of the resonant frequency was analyzed using an equation
      Deltaf=a(0) + a(1) e(-t/tau(1)) + a(2) e(-t/tau(2)). The relationship between the
      total a(0) values and the Cu(2+) concentration was discussed.

PMID- 11245893
TI  - Optimizing the immobilization of single-stranded DNA onto glass beads.
AB  - The attachment of single-stranded DNA to a solid support has many biotechnology
      and molecular biology applications. This paper compares different immobilization
      chemistries to covalently link single-stranded DNA (20 base pairs), oligo(1),
      onto glass beads via a 5'-amino terminal end. Immobilization methods included a
      one-step 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and a two-step EDC
      reaction to succinylated and PEG-modified glass beads. The third method used 1,4
      phenylene diisothiocyanate to immobilize oligo(1) to aminopropyl glass beads. The
      influence of coupling buffer, oligo(1) concentration, and EDC concentration was
      also investigated. The one-step EDC-mediated procedure with succinylated or PEG
      modified beads in 0.1 M MES buffer, pH 4.5, resulted in the highest
      immobilization efficiency, 82-89%. EDC concentrations greater than 50 mM and
      oligo(1) concentrations of 3 microg/g bead were required for effective
      immobilization. A complementary oligonucleotide, oligo(2), was able to hybridize
      to the immobilized oligo(1) with a 58% efficiency. This oligonucleotide was
      subsequently released at 70 degrees C. The relationship between the surface
      density of oligo(1) and the hybridization efficiency of the complementary
      oligonucleotide is described.

PMID- 11245894
TI  - A simple technique for the simultaneous determination of molecular weight and
      activity of superoxide dismutase using SDS-PAGE.
AB  - A direct and rapid SDS-PAGE staining method for in situ identification of
      activity and molecular weight of superoxide dismutase following denaturing
      treatment has been developed. This technique was based on the removal of SDS
      after SDS-PAGE and two-step staining procedures of the SDS-polyacrylamide gel to
      present the achromatic activity-zones of the enzymes. We demonstrated that the
      detection sensitivity of SDS-PAGE staining method was the same as the traditional
      xanthine oxidase-NBT solution assay. Through the SDS-PAGE staining method, three
      classes of superoxide dismutases with distinct molecular sizes were identified in
      situ. Moreover, activity of copper and zinc containing superoxide dismutase in
      crude extracts of Escherichia coli and Actinobacillus pleuropneumoniae was
      significantly enhanced using the two-step staining procedure.

PMID- 11245895
TI  - Recombinant human nerve growth factor for clinical trials: protein expression,
      purification, stability and characterisation of binding to infusion pumps.
AB  - Nerve growth factor (NGF) has been suggested to be of therapeutic benefit to
      patients with Alzheimer's disease. One of the early changes in this disease is a
      loss of cholinergic function within the brain, and NGF is able to rescue
      cholinergic neurons both in vitro and in vivo. We describe the production of
      recombinant human beta-NGF (rhNGF), using baculovirus infection of insect cells;
      its purification, formulation and subsequent stability for use in clinical
      trials. Tests were also carried out to monitor release of protein from infusion
      pumps and catheters for intracerebroventricular administration (icv). Initial
      problems with non-specific binding were overcome using a blocking formula.

PMID- 11245896
TI  - Tailored biopolymers.

PMID- 11245897
TI  - Biodegradation of polyesters containing aromatic constituents.
AB  - Polymers, which undergo a controlled biological degradation by micro-organisms
      came to remarkable interest during the last years. Composting for instance could
      so be established as an alternative waste management system for parts of the
      plastic waste. Within this group of innovative polymer, polyesters play a
      predominant role, due to their potentially hydrolyzable ester bonds. While
      aromatic polyesters such as poly(ethylene terephthalate) exhibit excellent
      material properties but proved to be almost resistant to microbial attack, many
      aliphatic polyesters turned out to be biodegradable but lack in properties, which
      are important for application. To combine good material properties with
      biodegradability, aliphatic-aromatic copolyesters have been developed as
      biodegradable polymers for many years. This article reviews the attempts to
      combine aromatic and aliphatic structures in biodegradable plastics and work,
      which has been done to evaluate the degradation behaviour and environmental
      safety of biodegradable polyesters, containing aromatic constituents.

PMID- 11245898
TI  - Factors involved in the regulatory network of polyhydroxyalkanoate metabolism.
AB  - Polyhydroxyalkanoates (PHAs) are bacterial storage materials which are
      accumulated by various bacteria under unbalanced growth conditions. Although PHAs
      are produced in larger amounts and are studied because of their plastic material
      properties, not much is known about the regulation of PHA accumulation and the
      regulatory interactions with the general cell metabolism. In this report, we
      point out the diversity of regulatory mechanisms involved in PHA metabolism, and
      present examples for factors acting at the transcription or enzymatic level.

PMID- 11245899
TI  - Production of PHA from starchy wastewater via organic acids.
AB  - Polyhydroxyalkanoate (PHA) was produced from a starchy wastewater in a two-step
      process of microbial acidogenesis and acid polymerization. The starchy organic
      waste was first digested in a thermophilic upflow anaerobic sludge blanket (UASB)
      reactor to form acetic (60-80%), propionic (10-30%) and butyric (5-40%) acids.
      The total volatile fatty acids reached 4000 mg l(-1) at a chemical oxygen demand
      (COD) loading rate of 25-35 g l(-1) day(-1). A carbon balance indicates that up
      to 43% of the organic carbon in the starchy waste went to the organic acids and
      the rest to biogas, volatile suspended solids and residual sludge accumulated in
      the reactor. The acid composition profile was affected by COD loading rate: a
      medium rate around 9 g l(-1) day(-1) gave a high propionic acid content (29% wt)
      and a high rate around 26 g l(-1) day(-1) led to a high butyric acid content (34%
      wt). The acids in the effluent solution after microfiltration were utilized and
      polymerized into PHA by bacterium Alcaligenes eutrophus in a second reactor.
      Fifty grams of PHA was produced from 100 g total organic carbon (TOC) utilized, a
      yield of 28% based on TOC, which is comparable with 55 g PHA per 100 g TOC of
      pure butyric and propionic acids used. PHA formation from individual acids was
      further investigated in a semi-batch reactor with three acid feeding rates. With
      a limited nitrogen source (80-100 mg NH(3) per liter), the active biomass of A.
      eutrophus, not including the accumulated PHA in cells, was maintained at a
      constant level (8-9 g l(-1)) while PHA content in the cell mass increased
      continuously in 45 h; 48% PHA with butyric acid and 53% PHA with propionic acid,
      respectively. Polyhydroxybutyrate was formed from butyric acid and
      poly(hydroxybutyrate-hydroxyvalerate) formed from propionic acid with 38%
      hydroxyvalerate.

PMID- 11245900
TI  - Degradation of natural and synthetic polyesters under anaerobic conditions.
AB  - Often, degradability under anaerobic conditions is desirable for plastics claimed
      to be biodegradable, e.g. in anaerobic biowaste treatment plants, landfills and
      in natural anaerobic sediments. The biodegradation of the natural polyesters
      poly(beta-hydroxybutyrate) (PHB), poly(beta-hydroxybutyrate-co-11.6%-beta
      hydroxyvalerate) (PHBV) and the synthetic polyester poly(epsilon-caprolactone)
      (PCL) was studied in two anaerobic sludges and individual polyester degrading
      anaerobic strains were isolated, characterized and used for degradation
      experiments under controlled laboratory conditions. Incubation of PHB and PHBV
      films in two anaerobic sludges exhibited significant degradation in a time scale
      of 6-10 weeks monitored by weight loss and biogas formation. In contrast to
      aerobic conditions, PHB was degraded anaerobically more rapidly than the
      copolyester PHBV, when tested with either mixed cultures or a single strained
      isolate. PCL tends to degrade slower than the natural polyesters PHB and PHBV.
      Four PHB and PCL degrading isolates were taxonomically identified and are
      obviously new species belonging to the genus Clostridium group I. The
      depolymerizing enzyme systems of PHB and PCL degrading isolates are supposed to
      be different. Using one isolated strain in an optimized laboratory degradation
      test with PHB powder, the degradation time was drastically reduced compared to
      the degradation in sludges (2 days vs. 6-10 weeks).

PMID- 11245901
TI  - Producing poly-3-hydroxybutyrate with a high molecular mass from methane.
AB  - Poly-3-hydroxybutyrate (PHB) and other polyesters can be produced by various
      species of bacteria. Of the possible carbon sources, methane could provide a
      suitable substrate for the production of PHB. Methane is cheap and plentiful -
      not only as natural gas, but also as biogas. The methanotrophic strain
      Methylocystis sp. GB 25 DSMZ 7674 is able to accumulate PHB in a brief non
      sterile process. The studies were carried out using a 7-l and a 70-l pressure
      bioreactor. Cultivation was performed in two stages: a continuous growth phase
      (dilution rate 0.17 h(-1)) and a PHB accumulation phase under deficiency
      conditions of an essential nutrient (ammonium, phosphorus or magnesium) in batch
      culture. The PHB content of biomass was as high as 51%; efficiency was highest
      during the first 5 h of the product formation process. The maximum PHB yield
      relative to the methane consumed was estimated to be 0.55 g g(-1). The PHB
      produced is of very high quality, having a high molecular mass of up to 2.5x10(6)
      Da.

PMID- 11245902
TI  - Versatility of biodegradable biopolymers: degradability and an in vivo
      application.
AB  - Biodegradable materials have various important applications in the biomedical
      field. There are basically two groups of polyesters which have significant
      importance in this field. These are polylactides and polyhydroxybutyrates. Both
      groups degrade via hydrolysis with the rates of degradation depending on medium
      properties such as pH, temperature, solvent and presence of biocatalysts, as well
      as on chemical compositions. In order for these biomaterials to be suitable for
      use in load bearing applications without deformation or warping their strengths
      and their capability to maintain their form must be improved. To insure
      dimensional stability during degradation and to match modulus and strength to
      that of bone, introduction of a reinforcing structure for those applications to
      plate fixation through the creation of an interpenetrating network might be a
      feasible approach. In this study, poly(lactide-co-glycolide) (PLGA), was the
      major structural element to be strengthened by a three-dimensional network or
      "scaffold" of another biodegradable polymer, poly(propylene fumarate) (PPF). PPF
      would be crosslinked with a biocompatible vinyl monomer, vinylpyrrolidone (VP).
      Three different approaches were tested to create dimensionally stable bone
      plates. First, via in situ crosslinking of PPF in the presence of PLGA. Secondly,
      by blending of precrosslinked PPF with PLGA. Finally, by simultaneous
      crosslinking and molding of the PLGA, PPF and VP. These were compared against
      extruded or compression molded PLGA controls. Results showed that compression
      molding at room temperature followed by crosslinking under pressure at elevated
      temperature and subsequently by gamma-irradiation appeared to yield the most
      favorable product as judged by swelling, hardness and flexural strength data. The
      composition of the implant material, PLGA(3):PPF(1):VP(0.7), appeared to be
      suitable and formed the compositional and procedural basis for in vivo
      biocompatibility studies.

PMID- 11245903
TI  - Biodegradable fibres spun from poly(lactide) generated by reactive extrusion.
AB  - Poly(lactide) (PLA) was spun both in a high speed spinning process with take-up
      velocities of 1000-5000 m min(-1) and in a spin drawing process at draw ratios of
      4-6. The effect of the melt spinning conditions on the development of the
      structural hierarchy in the fibres and the relations to the textile physical
      properties were investigated. The PLA fibres were characterised with regard to
      the degree of crystallinity by DSC and WAXS, the orientation by WAXS and
      birefringence, and the stress-strain behaviour. The maximum physical break stress
      and the E-modulus observed in the spin drawn fibres were about 490 MPa and 6.3
      GPa, respectively, at an elongation at break of 30%. The PLA was a copolymer of L
      lactide (92 wt.%) and meso-lactide (8 wt.%) and was generated by reactive
      extrusion polymerisation. The PLA virgin pellets were analysed regarding their
      degradation during the spinning processes. Their thermal and rheological
      properties were determined by DSC and dynamic rheological measurements,
      respectively, to derive suitable parameters for the melt spinning processes.

PMID- 11245904
TI  - Targeting of superoxide dismutase and catalase to vascular endothelium.
AB  - Reactive oxygen species, such as superoxide anion (O2(-)) and H2O2, cause
      oxidative stress in endothelial cells, a condition implicated in the pathogenesis
      of many cardiovascular and pulmonary diseases. Antioxidant enzymes, superoxide
      dismutases (SOD, converting superoxide anion into H2O2) and catalase (converting
      H2O2 into water), are candidate drugs for augmentation of antioxidant defenses in
      endothelium. However, SOD and catalase undergo fast elimination from the
      bloodstream, which compromises delivery and permits rather modest, if any,
      protection against vascular oxidative stress. Coupling of polyethylene glycol
      (PEG) to the enzymes and encapsulating them in liposomes increases their
      bioavailability and enhances their protective effect. Chemical modifications and
      genetic manipulations of SOD and catalase have been proposed in order to provide
      more effective delivery to endothelium. For example, chimeric protein constructs
      consisting of SOD and heparin-binding peptides have an affinity for charged
      components of the endothelial glycocalix. However, the problem of developing a
      more effective and precise delivery of the drugs to endothelial cells persists.
      Endothelial surface antigens may be employed to provide targeting and subcellular
      addressing of drugs (vascular immunotargeting strategy). Thus, SOD and catalase
      conjugated to antibodies directed against the constitutively expressed
      endothelial antigens, angiotensin-converting enzyme (ACE) and adhesion molecules
      (ICAM-1 or PECAM-1), bind to endothelium in intact animals after intravascular
      administration, accumulate in the pulmonary vasculature, enter endothelial cells
      and augment their antioxidant defenses. Such immunotargeting strategies may
      provide secondary therapeutic benefits by inhibiting the function of target
      antigens. For example, blocking of ICAM-1 and PECAM-1 by carrier antibodies may
      attenuate inflammation and leukocyte-mediated vascular damage. Additional studies
      in animal models of vascular oxidative stress are necessary in order to more
      fully characterize potential therapeutic effects and limitations of targeting of
      antioxidant enzymes to endothelial cells.

PMID- 11245905
TI  - Effect of therapeutic ultrasound on partition and diffusion coefficients in human
      stratum corneum.
AB  - Application of various enhancers including ultrasound and chemicals has been
      shown to enhance transdermal drug transport. Most of these enhancers increase
      transdermal transport by increasing either partition or diffusion coefficients in
      lipid bilayers. Although the effect of such enhancers on skin permeability has
      been measured in many cases, the effect of the same enhancers on solute partition
      and diffusion coefficients has not been measured since such measurements are
      difficult. In this paper, we describe application of a new method that can be
      used to determine the effect of enhancers on partition and diffusion
      coefficients. This method is based on two independent measurements of the
      transport properties of the SC and a theoretical model. This method was tested
      for five solutes including estradiol, napthol, aldosterone, lidocaine, and
      testosterone. Measurements based on our method showed that the primary effect of
      therapeutic ultrasound (1 MHz) is on diffusion coefficient and not partition
      coefficient. Specifically, ultrasound enhanced diffusion coefficients of these
      solutes by up to 15-fold. However, it did not significantly enhance partition
      coefficients. The method described in this paper is quite general and can be used
      to measure the effect of various enhancers on partition and diffusion
      coefficients.

PMID- 11245906
TI  - Release of BSA from poly(ortho ester) extruded thin strands.
AB  - A solventless procedure was used where powdered polymer and micronized protein
      were intimately mixed and then extruded into 1 mm strands that were cut to the
      desired length. The polymers used were poly(ortho esters) specifically designed
      to allow extrusion in the neighborhood of 70 degrees C. At these temperatures
      many proteins maintain activity in the dry state. In vitro erosion and BSA
      release results indicate that after a fairly long lag-time, BSA release and
      polymer erosion occur concomitantly indicating an erosion-controlled process. The
      lag-time could be eliminated by the addition to the mixture prior to extrusion
      between 1 and 5 wt% poly(ethylene glycol) or its methoxy derivatives. The lag
      time could also be eliminated by using an AB-block copolymer where A is
      poly(ortho ester) and B is poly(ethylene glycol).

PMID- 11245907
TI  - In vitro uptake of polystyrene microspheres: effect of particle size, cell line
      and cell density.
AB  - Uptake of polycation-DNA particles is the first step in achieving gene delivery
      with non-viral vehicles. One of the important characteristics determining uptake
      of DNA particles is their size. Here we have characterized the ability of several
      cell lines to internalise labelled polystyrene microspheres of different sizes.
      All the cell lines tested ingested 20-nm microspheres avidly. With larger
      microspheres (93, 220, 560 and 1010 nm) cell type as well as growth related
      differences were observed. Whereas some cell lines (HUVEC, ECV 304 and HNX 14C)
      took up microspheres up to 1010 nm even when the cells were confluent, others did
      not take up many microspheres larger than 93 nm (Hepa 1-6 and HepG2). In one cell
      line (KLN 205), uptake of 93-, 220- and 560-nm microspheres was avid in growing
      cells, but not detectable when they were confluent. In KLN 205 cells, a good
      correlation was found between the uptake of 560-nm microspheres and the uptake of
      a peptide-DNA polyplex formulation, when it was prepared under conditions leading
      to small particle sizes. Little correlation was found when the polyplex
      formulation was allowed to aggregate.

PMID- 11245908
TI  - Effects of emulsifiers on the controlled release of paclitaxel (Taxol) from
      nanospheres of biodegradable polymers.
AB  - Paclitaxel (Taxol) is an antineoplastic drug effective for various cancers
      especially ovarian and breast cancer. Due to its high hydrophobicity, however, an
      adjuvant such as Cremophor EL has to be used in its clinical administration,
      which causes serious side-effects. Nanospheres of biodegradable polymers could be
      an ideal solution. This study investigates the effects of various emulsifiers on
      the physical/chemical properties and release kinetics of paclitaxel loaded
      nanospheres fabricated by the solvent extraction/evaporation technique. It is
      shown that phospholipids could be a novel type of emulsifiers. The nanospheres
      manufactured with various emulsifiers were characterized by laser light
      scattering for their size and size distribution; scanning electron microscopy
      (SEM) and atomic force microscopy (AFM) for their surface morphology; zeta
      potential analyser for their surface charge; and, most importantly, X-ray
      photoelectron spectroscopy (XPS) for their surface chemistry. The encapsulation
      efficiency and in vitro release profile were measured by high performance liquid
      chromatography (HPLC). It is found that dipalmitoyl-phosphatidylcholine (DPPC)
      can provide more complete coating on the surface of the products which thus
      results in a higher emulsifying efficiency compared with polyvinyl alcohol (PVA).
      Our result shows that the chain length and unsaturation of the lipids have a
      significant influence on the emulsifying efficiency. Phospholipids with short and
      saturated chains have excellent emulsifying effects.

PMID- 11245909
TI  - Carrier and dose effects on the pharmacokinetics of T-0128, a camptothecin
      analogue-carboxymethyl dextran conjugate, in non-tumor- and tumor-bearing rats.
AB  - T-0128 is a novel camptothecin (CPT) analogue (T-2513: 7-ethyl-10-aminopropyloxy
      CPT)-carboxymethyl (CM) dextran conjugate via a Gly-Gly-Gly linker, with a
      molecular weight (MW) of 130 kDa. Our previous studies demonstrated that T-0128
      has strong antitumor activity against human tumor xenografts that are highly
      refractory to CPT analogues attributable to the passive tumor targeting of
      released T-2513. This study examines the effects of carrier, dose, and tumor on T
      0128 pharmacokinetics. To study carrier effect, tumor-bearing rats received one
      i.v. injection of fluorescein isothiocyanate (FITC)-labeled CM dextran with a
      different degree of substitution (DS) of the carboxymethylated groups and a
      different MW. Results showed that CM dextran from Dextran T-110 (MW 110 kDa) with
      a DS value of 0.4 is an appropriate drug carrier for T-0128 regarding plasma half
      life and passive tumor targeting. To study dose and tumor effects, non-tumor- and
      tumor-bearing rats were treated with T-0128 doses ranging from 1 to 25 mg/kg
      (based on the amount of T-2513 bound to CM dextran). Dose-dependent
      pharmacokinetics of T-0128 were observed in both kinds of rats. The presence of
      tumor reduced the plasma half-life and systemic exposure of T-0128. The
      saturation of hepatic and splenic tissue uptake clearances (CLups), and a large
      contribution of the tumor CLup to the total body clearance explain these results.
      Overall, our data provide a rationale for the selection of the carrier for T-0128
      and a need for pharmacokinetic studies to evaluate the influences of tumor on the
      drug disposition.

PMID- 11245910
TI  - Sustained elevated plasma aprotinin concentration in mice following
      intraperitoneal injections of w/o emulsions incorporating aprotinin.
AB  - This study was initiated to test the feasibility of w/o emulsions as a sustained
      release system for aprotinin following intraperitoneal injection in mice. The
      emulsion was well tolerated in mice and sustained release was observed over a
      period of 96 h. The time for maximum plasma concentration of aprotinin was 10 min
      and 12 h after injection of a control solution and the emulsion dosage form,
      respectively. Furthermore, the hemolytic activity of the emulsion constituents
      was low indicating a low acute toxicological potential of the emulsion. The
      present study also showed that the lipolytic activity in peritoneal exudate from
      mice is important for the clearance of oily vehicles from the peritoneal cavity
      with lipolytic rate constants ranging from 50 to 130 nmol free fatty acid
      released/min/mg exudate protein at 37 degrees C, pH 8.5. It was concluded that
      the w/o emulsion was well suited to provide sustained elevated plasma aprotinin
      concentrations in mice.

PMID- 11245911
TI  - In vitro transdermal iontophoretic transport of timolol maleate: effect of age
      and species.
AB  - Transdermal iontophoresis would be a promising method for the systemic delivery
      of water soluble and ionic drugs of relatively high molecular size, including
      peptides. In the present study, the effect of biological parameters such as age
      of the animal and species variation (rat, rabbit, mouse, guinea pig and human) on
      the transdermal iontophoretic transport was studied using timolol maleate (TM) as
      a model drug. The iontophoretic transport of TM across the skins obtained from
      the rats of different age groups was found to be similar. The results of the
      present study suggest that the age of the animal (Wistar rats: 1-8 months) did
      not appear to influence the transdermal iontophoretic transport of TM
      significantly. The amount of TM transported during iontophoresis (2 h) was
      significantly different among the different skin species. But the total amount of
      TM transported up to 24 h (2 h iontophoresis+22 h post-iontophoretic passive
      diffusion) was not significantly different among the different species studied.
      The present study provides further evidence that iontophoresis technique reduces
      the interspecies differences in the transdermal permeation of drugs, which is
      normally observed in passive diffusion of drugs. However, it must be noted that
      excised skins have been used in the present study to investigate the role of age
      and species variation on the iontophoretic transport of TM. The influence of
      these parameters under in vivo conditions might be different considering the
      physiological differences in different species and in the animals of different
      age groups.

PMID- 11245912
TI  - Preclinical evaluation of pharmacokinetic-pharmacodynamic rationale for oral CR
      metformin formulation.
AB  - We examined the pharmacokinetic (PK) and pharmacodynamic (PD) rationales to
      develop controlled release (CR) formulations of metformin. Unrestrained diabetic
      rats received the drug as intravenous bolus (i.v.), oral solution (p.o.), intra
      duodenal bolus, 4-h infusion, or intra-colonic bolus. In addition, we developed
      two CR-gastroretentive dosage forms (CR-GRDF) that released the drug over 3 or 6
      h (in vitro), and retained in the rats' stomach for 8-10 h. Metformin exhibited
      flip-flop PK. The colonic absorption was low but sustained and was associated
      with highly variable glucose-lowering effects, thus providing a PK rationale to
      develop CR-GRDF. In addition, the glucose-lowering effect was greater following
      p.o. vs. i.v. administration, despite equivalent AUC, indicating a first pass PD
      effect, thus, adding a PD rationale to develop metformin CR-GRDF. When
      administered to the diabetic rats, CR-GRDFs produced bioavailability and extent
      of glucose-lowering effects that were similar to those of the duodenal infusion
      and p.o. metformin administration. These findings are attributed to the
      adsorption of metformin to the intestine that yields slow and prolonged
      absorption even following p.o. administration of drug solution. The data
      indicates that unless the CR formulation could significantly extend the
      absorption period, it is not likely to improve glucose-lowering efficacy.

PMID- 11245913
TI  - Preparation and characterisation of rose Bengal-loaded surface-modified albumin
      nanoparticles.
AB  - Surface-modified albumin nanoparticles were prepared from two poly(ethylene
      glycol)-human serum albumin conjugates: poly(thioetheramido acid)-poly(ethylene
      glycol) copolymer-grafted HSA (HSA-PTAAC-PEG) and methoxy poly(ethylene glycol)
      grafted HSA (HSA-mPEG). Rose bengal (RB) was used as a model drug for
      encapsulation into the nanoparticles either during the particle production or by
      adsorption post particle preparation. The drug incorporation and release was
      affected by the different production methods and the different polymer
      compositions. When RB was loaded in HSA and HSA/HSA-PTAAC-PEG nanoparticles, up
      to 5% (w/w) drug content was achieved. The drug loading in HSA-mPEG nanoparticles
      was much lower and the results from the microcalorimetry study indicated that the
      low loading efficiency was due to less drug-protein binding sites available in
      the HSA-mPEG molecule as compared to the HSA molecule. The release of RB from the
      albumin nanoparticles was very slow in PBS and dramatically accelerated in the
      presence of trypsin. Compared with unmodified nanoparticles, the slower release
      of RB from the surface-modified HSA nanoparticles in the presence of the enzyme
      suggested that the existence of a steric hydrophilic barrier on the surface of
      the nanoparticles made digestion of the nanoparticles more difficult.

PMID- 11245914
TI  - NSAIDs bound to methacrylic carriers: microstructural characterization and in
      vitro release analysis.
AB  - Chemically controlled drug delivery systems or 'polymeric drugs' based on
      copolymers of 2-hydroxyethyl methacrylate, HEMA, and five methacrylic derivatives
      which incorporate ibuprofen or ketoprofen in their chemical structure by means of
      labile ester bonds, MAI, MAK, MAEK, MEI and MEK, have been prepared by free
      radical polymerization in solution at 50 degrees C. Three different spacers have
      been incorporated to the monomer structure: an aromatic amide, an aliphatic ester
      and a combined aromatic amide/aliphatic ester. Copolymerization reactions of the
      methacrylamide derivatives with HEMA follow the terminal model with reactivity
      ratio values, determined by the Tidwell and Mortimer (J. Polym. Sci. A 1965;3:369
      378) non-linear least-squares treatment, of r(MAI)=0.38, r(HEMA)=1.69;
      r(MAK)=0.30, r(HEMA)=0.48; and r(MAEK)=0.66, r(HEMA)=2.85. From these values and
      considering that the methacrylates MEI and MEK are structurally related to HEMA,
      the microstructural analysis give us a random distribution of the monomeric
      units. The HEMA-rich copolymers, used for the in vitro experiments, showed a very
      high population of sequences with the active residue isolated by HEMA units. The
      in vitro release experiments were carried out at pH 7.4 and 9, using six
      different compositions for each copolymer system (1, 2.5, 5, 10, 20 and 30 wt% of
      the active acrylic monomer). The results show a controlled release in terms of
      weeks with very different profiles which depend on the type of spacer (the
      aromatic ester is more susceptible to hydrolysis than the aliphatic one), drug
      (ketoprofen release rate is higher than the ibuprofen one), composition of the
      copolymer (as a general rule, the release rate increases with the content of the
      attached drug until some composition where this effect is reverted because of the
      global increase in hydrophobicity) and pH (the release rate is noticeably higher
      in a strong basic medium, pH 9).

PMID- 11245915
TI  - Lipid-based microtubular drug delivery vehicles.
AB  - Lipid microtubules that self-assemble from a diacetylenic lipid are suitable
      structures for the sustained release of bioactive agents. Microtubules were
      loaded with agents under aqueous conditions and embedded in an agarose hydrogel
      for localization at areas of interest. Protein release from our microtubule
      hydrogel delivery system was characterized in vitro, and in vivo biocompatibility
      was examined. The influences of protein molecular weight and initial loading
      concentration on release profile were evaluated by releasing test proteins
      myoglobin, albumin, and thyroglobulin. Protein molecular weight inversely
      affected the release rate, and loading with a higher protein concentration
      increased the mass but not the percent of initially loaded protein released
      daily. Preservation of protein activity was demonstrated by the ability of a
      neurotrophic factor released from the delivery system to induce neurite extension
      in PC12 cells. Bovine aortic smooth muscle cells co-cultured with the microtubule
      hydrogel system showed no evidence of cytotoxicity and proliferated in the
      presence of the microtubules. Subcutaneous implantation of microtubules in
      rodents revealed no significant inflammatory response after 10 days. Our
      microtubule-hydrogel system is useful for applications where sustained release
      without contact between agent and organic solvents is desired.

PMID- 11245916
TI  - Evidence for an endocannabinoid system in the central nervous system of the leech
      Hirudo medicinalis.
AB  - In invertebrates, like Hydra and sea urchins, evidence for a functional
      cannabinoid system was described. The partial characterization of a putative CB1
      cannabinoid receptor in the leech Hirudo medicinalis led us to investigate the
      presence of a complete endogenous cannabinoid system in this organism. By using
      gas chromatography-mass spectrometry, we demonstrate the presence of the
      endocannabinoids anandamide (N-arachidonoylethanolamine, 21.5+/-0.7 pmol/g) and 2
      arachidonoyl-glycerol (147.4+/-42.7 pmol/g), and of the biosynthetic precursor of
      anandamide, N-arachidonylphosphatidyl-ethanolamine (16.5+/-3.3 pmol/g), in the
      leech central nervous system (CNS). Anandamide-related molecules such as N
      palmitoylethanolamine (32.4+/-1.6 pmol/g) and N-linolenoylethanolamine (5.8
      pmol/g) were also detected. We also found an anandamide amidase activity in the
      leech CNS cytosolic fraction with a maximal activity at pH 7 and little
      sensitivity to typical fatty acid amide hydrolase (FAAH) inhibitors. Using an
      antiserum directed against the amidase signature sequence, we focused on the
      identification and the localization of the leech amidase. Firstly, leech nervous
      system protein extract was subjected to Western blot analysis, which showed three
      immunoreactive bands at ca. approximately 42, approximately 46 and approximately
      66 kDa. The former and latter bands were very faint and were also detected in
      whole homogenates from the coelenterate Hydra vulgaris, where the presence of CB1
      like receptors, endocannabinoids and a FAAH-like activity was reported
      previously. Secondly, amidase immunocytochemical detection revealed numerous
      immunoreactive neurons in the CNS of three species of leeches. In addition, we
      observed that leech amidase-like immunoreactivity matches to a certain extent
      with CB1-like immunoreactivity. Finally, we also found that stimulation by
      anandamide of this receptor leads, as in mammals, to inhibition of cAMP
      formation, although this effect appeared to be occurring through the previously
      described anandamide-induced and CB1-mediated activation of nitric oxide release.
      Taken together, these results suggest the existence of a complete and functional
      cannabinoid system in leeches.

PMID- 11245917
TI  - Schizophrenia: elevated mRNA for dopamine D2(Longer) receptors in frontal cortex.
AB  - Because dopamine D2 receptors are the primary targets for antipsychotic drugs,
      including clozapine and quetiapine, and because some studies have found D2
      receptors to be elevated in schizophrenia, we examined the mRNA of three forms of
      the D2 receptor, particularly the new form of the dopamine D2 receptor,
      D2(Longer), in post-mortem brains from patients who died with schizophrenia.
      Using quantitative competitive RT-PCR (reverse transcriptase-polymerase chain
      reaction), the D2(Longer) mRNA was higher in the frontal cortex, compared to
      control tissues. The mRNA concentration of D2(Long) and D2(Short) was also higher
      in the frontal cortex, compared to control tissues. Although most of the
      schizophrenia patients had received different antipsychotic drugs for varying
      periods of time, the mRNA of D2(Longer), as well as that for D2(Long) and
      D2(Short), in such medicated tissues was similar to that in a frontal cortex
      tissue from a patient who had reliably never received antipsychotic drugs. It is
      possible, therefore, that the elevation of the mRNAs for D2(Longer), D2(Long) and
      D2(Short) in the frontal cortex may be related to the disease of schizophrenia
      itself.

PMID- 11245918
TI  - Effect of PS1 deficiency and an APP gamma-secretase inhibitor on Notch1 signaling
      in primary mammalian neurons.
AB  - Presenilin1 (PS1) has been implicated in normal Notch1 processing and signaling
      in several experimental systems. In the present study, the relationship between
      PS1 and Notch1 in mammalian neurons is studied by analyzing Notch1 cleavage and C
      terminal nuclear translocation as well as Notch1 signaling via the
      transactivation of a CBF1-luciferase reporter construct. We show that full-length
      Notch1 [N1(FL)] transfected into wild type (WT) primary neurons is cleaved in the
      presence of its biological ligand Delta (Dl) and translocated to the nucleus
      within 1--3 min of ligand addition. PS1 deficient neurons show normal Notch1
      insertion into the cellular membrane, yet lack Notch1 activation resulting in
      markedly inhibited nuclear translocation of the C-terminal Notch fragment (NICD).
      PS1 deficient neurons also have impaired Notch1 signaling which can be restored
      fully or partially to levels seen in WT littermates by transfection with WT or
      familial Alzheimer's disease-associated M146L mutant PS1, respectively. We also
      show that pharmacological inhibition of PS1-associated gamma-secretase activity
      parallels the effects of genetic PS1 deficiency in these assays. These results
      support the hypothesis that PS1 deficiency blocks neuronal Notch1 processing and
      signaling.

PMID- 11245920
TI  - Inhibition of MAO-A fails to alter cocaine-induced increases in extracellular
      dopamine and norepinephrine in rat nucleus accumbens.
AB  - Monoamine oxidase (MAO) inhibitors are being investigated as possible medications
      for cocaine dependence, but there are potential problems with this approach. In
      the present study, we tested the hypothesis that inhibition of catecholamine
      metabolism with the MAO-A inhibitor, clorgyline, might enhance cocaine-induced
      increases in extracellular dopamine and norepinephrine in rat nucleus accumbens.
      Male rats were pretreated with clorgyline (1 mg/kg, s.c.) or its saline vehicle
      (1 ml/kg, s.c.), and microdialysis probes were inserted into previously implanted
      guide cannulae. After overnight perfusion of the probes in situ, rats received an
      acute challenge injection of either cocaine (1 mg/kg, i.v.) or its saline vehicle
      (1 ml/kg, i.v.). Clorgyline pretreatment alone caused significant elevations in
      basal levels of dialysate norepinephrine but not dopamine. Cocaine administration
      elicited significant increases in extracellular dopamine and norepinephrine in
      all groups of rats, and this effect was not altered by clorgyline pretreatment.
      The 1 mg/kg dose of clorgyline decreased dopamine metabolites in postmortem brain
      tissue by more than 80%. Our data are consistent with clinical studies that
      demonstrate pretreatment with the MAO-B selective inhibitor, selegeline, fails to
      alter cocaine-induced subjective effects in human drug users. Moreover, these
      findings suggest that adverse consequences related to altered catecholamine
      transmission would not occur if patients taking phenelzine, a non-selective MAO
      inhibitor, relapsed and used cocaine.

PMID- 11245919
TI  - Selective inhibition of nicotinic cholinergic receptors by proadrenomedullin N
      terminal 12 peptide in bovine adrenal chromaffin cells.
AB  - We studied whether a novel proadrenomedullin derived peptide was present and what
      was its physiological function in cultured bovine adrenal chromaffin cells. We
      found a high level of proadrenomedullin N-terminal 12 peptide (PAMP-12) which
      consists of a peptide from 9th amino acid to 20th amino acid of proadrenomedullin
      N-terminal 20 peptide (PAMP-20). PAMP-12 was released from the cells along with
      catecholamine upon stimulation of nicotinic cholinergic receptors. When PAMP-12
      was added in the incubation medium, this peptide inhibited nicotinic receptor
      mediated catecholamine release and influx of Na(+) and Ca(2+) into the cells.
      PAMP-12 did not affect catecholamine release evoked by histamine or by
      depolarization by high concentration of potassium. PAMP-12 also inhibited
      synthesis of catecholamines as well as the activation of tyrosine hydroxylase by
      nicotinic stimulation. Thus, PAMP-12 is an endogenous peptide that regulates
      release and synthesis of catecholamines by acting on nicotinic cholinergic
      receptors in an autocrine manner in adrenal chromaffin cells.

PMID- 11245921
TI  - Splice isoforms of ubiquitous 6-phosphofructo-2-kinase/fructose-2,6
      bisphosphatase in human brain.
AB  - In human brain we were able to demonstrate sequence diversity of the ubiquitous 6
      phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2). Six
      different isoforms of PFK-2/FBPase-2, two of which are identical with the
      ubiquitous PFK-2/FBPase-2 and the inducible PFK-2, respectively, could be
      identified. The heterogeneity of human brain PFK-2/FBPase-2 isoforms is generated
      by alternative splicing. Three hitherto unrecognized exons were detected. The
      multiple PFK-2/FBPase-2 transcripts encode proteins which differ with respect to
      their length and to the amino acid composition of the carboxyl-termini. The
      isoform pattern of ubiquitous PFK-2/FBPase-2 is more complex in human brain than
      in skeletal muscle and liver.

PMID- 11245922
TI  - Aging selectively suppresses vasoactive intestinal peptide messenger RNA
      expression in the suprachiasmatic nucleus of the Syrian hamster.
AB  - Aging leads to many changes in the expression of circadian rhythms, including
      reduced amplitude, altered relationship to the environmental illumination cycle,
      and reduced sensitivity to phase resetting signals. Neuropeptide synthesizing
      neurons in the suprachiasmatic nucleus (SCN), the principal circadian pacemaker
      in mammals, play a role in regulating pacemaker function and in coupling the
      pacemaker to overt circadian rhythms. Aging may alter the activity of
      neuropeptide neurons in the SCN, which could be reflected in changes in mRNA
      expression. Therefore, this study investigated whether aging alters the level or
      rhythm of expression of neuropeptide mRNAs in the SCN of male Syrian hamsters, a
      well established model for the study of age-related changes in circadian rhythms.
      Three age groups of hamsters (young [3--5 months old], middle-aged [12--15 months
      old] and old [19--22 months old] were sacrificed at five times of day. Their
      brains were dissected and sections through the suprachiasmatic nucleus were
      prepared and used for in situ hybridization for mRNAs for vasoactive intestinal
      peptide (VIP), arginine vasopressin (AVP) and somatostatin (SS). Aging
      selectively decreased the SCN expression of VIP mRNA without affecting AVP mRNA
      or SS mRNA. Also, only AVP mRNA expression exhibited a robust 24-h rhythm, in
      contrast to previous findings in other species that VIP mRNA and SS mRNA, as well
      as AVP mRNA, exhibit 24-h rhythms in the SCN. The present findings suggest that
      age-related reductions in VIP mRNA expression may contribute to the alterations
      in entrainment and attenuated sensitivity to phase resetting signals that are
      characteristic of aging. Furthermore, the results demonstrate that neuropeptide
      gene expression in the SCN is differentially regulated by aging and varies among
      species.

PMID- 11245923
TI  - A functional retinoic acid response element (RARE) is present within the distal
      promoter of the rat gonadotropin-releasing hormone (GnRH) gene.
AB  - We previously demonstrated that all-trans-retinoic acid (all-trans-RA) regulates
      gonadotropin-releasing hormone (GnRH) release and gene expression in rat
      hypothalamic fragments and GT1-1 neuronal cells. Promoter analysis of rat GnRH
      gene revealed that the enhancing effect of all-trans-RA on GnRH transcription is
      mediated by cis-elements localized within --1640/--1438 of the rat GnRH promoter.
      In the present study, we attempted to localize functional retinoic acid response
      elements (RAREs) within the all-trans-RA-responsive region of the rat GnRH gene.
      Sequence analysis showed that there exist three putative repeats of AGGTCA
      related sequences (--1637/--1617, --1579/--1562, and --1494/--1470) within this
      promoter sequence. Among them, only the --1494/--1470 sequence could compete the
      specific binding of GT1-1 nuclear extracts to the consensus RARE (direct repeat
      of AGGTCA with a 5-bp spacer, DR-5) and vice versa in electrophoretic mobility
      shift assays. In addition, like consensus RARE, the --1494/--1470 sequence could
      confer all-trans-RA responsiveness when inserted into the upstream region of SV40
      promoter. Treatment of GT1-1 cells with all-trans- or 9-cis-RA increased the
      specific bindings of GT1-1 nuclear extracts to the consensus RARE and to the -
      1494/--1470 sequence while not affecting the specific binding to the cAMP
      response element (CRE). Both retinoids induced RARbeta gene expression in GT1-1
      cells. The --1494/--1470 sequence (5'-TCTTAGGACTCTGTGTGACCTAAGA) is similar to
      the direct repeat of TGACCT (complementary sequence of AGGTCA) with a spacer of 5
      bp (i.e. DR-5 in the reverse orientation). A mutation of the second core
      recognition motif of the --1494/--1470 sequence to a more divergent one from
      consensus RARE (from TGACCT to TTACAT) abolished the responsiveness to all-trans
      RA, whereas a mutation of first core recognition motif to a more TGACCT-like
      sequence (from AGGACT to TGAACT) increased the responsiveness to all-trans-RA.
      These results indicate that the --1494/--1470 sequence is indeed a weak but
      functional RARE of the modified DR-5 type. Taken together, these data indicate
      that all-trans-RA enhances GnRH transcription via functional RARE present in the
      distal region of the GnRH promoter.

PMID- 11245924
TI  - 9-cis-Retinoic acid represses transcription of the gonadotropin-releasing hormone
      (GnRH) gene via proximal promoter region that is distinct from all-trans-retinoic
      acid response element.
AB  - We previously reported an enhancing effect of all-trans-retinoic acid (all-trans
      RA) on gonadotropin-releasing hormone (GnRH) gene transcription via distal
      promoter elements of the rat GnRH gene. The present study examined the effects of
      another biologically active retinoid, 9-cis-retinoic acid (9-cis-RA), on GnRH
      transcription in GT1-1 cells. Similar to the action of all-trans-RA, 9-cis-RA
      significantly induced the luciferase activity of the strong retinoic acid
      response element (RARE) reporter construct, 3X beta RARE-Luc, by about 60-fold,
      indicating that GT1-1 cells are also responsive to 9-cis-RA. In contrast to the
      stimulatory effect of all-trans-RA on GnRH transcription, 9-cis-RA inhibited the
      GnRH promoter activity in a dose- and time-dependent manner. Significant
      inhibition by 9-cis-RA required at least an 18 h treatment and a further decrease
      of GnRH promoter-driven luciferase activity was observed up to 48 h of
      incubation. Accordingly, GnRH mRNA levels were decreased by 9-cis-RA treatment in
      a similar dose- and time-related manner, indicating that mouse GnRH expression is
      also negatively regulated by 9-cis-RA. Transient transfections of serial deletion
      constructs of the rat GnRH promoter revealed that the --230/--110 sequence of the
      rat GnRH promoter is responsible for 9-cis-RA-induced inhibition of GnRH
      transcription. Within this region, however, no consensus retinoid X receptor
      response element was found. To gain insights into the role of retinoid X
      receptors (RXRs) in GnRH expression, we examined the effects of RXR
      overexpression on GnRH transcriptional activity. Interestingly, co-transfection
      of RXR overexpression vectors significantly increased the GnRH promoter-driven
      luciferase activity, while treatment with 9-cis-RA not only nullified the
      enhancing effect of RXR overexpression but also decreased the basal GnRH promoter
      driven luciferase activity by 50% compared to vehicle-treated controls. This
      implies that RXRs in the absence of its cognate ligand 9-cis-RA contribute to the
      maintenance of basal GnRH gene transcription. Northern blot analysis revealed
      that 9-cis-RA, but not all-trans-RA, down-regulated RXR beta expression in GT1-1
      cells, suggesting that one possible mechanism of 9-cis-RA-induced repression
      involves down-regulation of RXR expression. In conclusion, the present study
      clearly demonstrates that 9-cis-RA is a negative regulator of GnRH gene
      expression in immortalized GnRH neurons.

PMID- 11245925
TI  - Characterization of mouse brain-specific angiogenesis inhibitor 1 (BAI1) and
      phytanoyl-CoA alpha-hydroxylase-associated protein 1, a novel BAI1-binding
      protein.
AB  - Previously, PAHX-AP1 (PAHX-associated protein 1) was isolated as a novel protein
      to interact with Refsum disease gene product (phytanoyl-CoA alpha-hydroxylase,
      PAHX) and specifically expressed in mouse brain. PAHX-AP1 is also suggested to be
      involved in the development of the central neurologic deficits of Refsum disease.
      To clarify its function, we have searched for proteins that associate with PAHX
      AP1 via yeast two-hybrid system. We found that PAHX-AP1 interacts with the
      cytoplasmic region of human brain-specific angiogenesis inhibitor 1 (hBAI1), and
      isolated murine homolog of hBAI1. Structural analysis of the PAHX-AP1 with three
      reported hBAI-associated proteins (BAP) revealed no homology among them, and we
      designated PAHX-AP1 as BAP4. The ability of BAP4 to interact with BAI1 was
      confirmed by pulling-down BAI1 with GST-BAP4 protein and immunoprecipitation
      study using brain lysate. Northern and Western blot analyses demonstrated a
      unique pattern of BAI1 expression in the brain. The peak level of BAI1 was
      observed 10 days after birth. In situ hybridization analyses of the brain showed
      the same localization of BAI1 as BAP4, such as most neurons of cerebral cortex,
      hippocampus, and V, VI, VII, VIII, and XII nuclei. Because BAI1 possessed
      thrombospondin-type 1 repeats in its extracellular region, changes of BAI1
      expression were examined in the focal cerebral ischemia model. The BAI1
      expression decreased on the ischemic side after 24 h but BAP4 was not changed
      after the time-course of ischemia. Our results indicate that expression and
      localization of BAI1 in the brain is correlated with BAP4, and that BAI1 is
      involved in inhibition of angiogenesis and neuronal differentiation.

PMID- 11245927
TI  - Molecular targets of disulfiram action on song maturation in zebra finches.
AB  - Disulfiram, an aldehyde dehydrogenase inhibitor, interferes with normal song
      maturation when applied to brain nucleus HVC of male zebra finches. We present
      here evidence from Western blots and enzymatic assays showing that known
      disulfiram targets other than retinaldehyde-specific aldehyde dehydrogenase
      (zRalDH) are absent in HVC. These findings are consistent with the conclusion
      that disulfiram disrupts song maturation by interfering with retinoic acid
      production.

PMID- 11245926
TI  - Association of membrane-bound amyloid precursor protein APP with the
      apolipoprotein E receptor LRP.
AB  - In order to identify cell surface proteins that interact with the amyloid
      precursor protein (APP), we biotinylated H4 human neuroglioma cells in culture
      with a water soluble biotinylating agent, immunoprecipitated APP with an antibody
      specific to the intracellular domain, and probed the precipitated proteins with
      anti-biotin. In human neuroglioma cells overexpressing APP751, we found a high
      molecular weight protein that immunoprecipitated with APP. This band was
      identified as the low density lipoprotein receptor-related protein (LRP) by three
      criteria: first, the band immunolabeled with anti-LRP antibodies; second, the
      band bound the LRP receptor associated protein, RAP; and third, this band was
      present in LRP-expressing fibroblasts, but not LRP-deficient fibroblasts. In
      complementary experiments, we found that APP co-precipitated with LRP, with a
      preference for an isoform of APP containing the Kunitz protease inhibitor domain.
      Interaction of APP and LRP on the surface of living cells was demonstrated by
      crosslinking APP and LRP with the water-soluble cross-linking agent BS(3). APP
      and LRP were shown by confocal microscopy to colocalize in perinuclear
      structures, but to primarily remain separate in vesicles and on the cell surface.
      We propose that full-length APP can transiently interact with the receptor LRP on
      the cell surface, affecting the processing and intracellular transport of APP.

PMID- 11245928
TI  - Expression of aldose reductase and sorbitol dehydrogenase genes in Schwann cells
      isolated from rat: effects of high glucose and osmotic stress.
AB  - To investigate the polyol pathway activity in Schwann cells, we determined the
      mRNA levels of aldose reductase (AR) and sorbitol dehydrogenase (SDH) in cultured
      cells under hyperglycemic or hyperosmotic conditions using competitive RT-PCR
      technique. The expressions of AR and SDH mRNAs in Schwann cells were unaltered by
      high (30 mM) glucose content in the medium. On the other hand, osmotic stress
      elicited significant increases in AR mRNA without any effect on SDH mRNA
      expression. The levels of AR mRNA determined by this RT-PCR system were
      significantly correlated with AR activity, as well as the levels of sorbitol
      accumulated in Schwann cells cultured under hyperosmotic conditions. These
      findings suggest that in contrast to the induction of AR expression by osmotic
      stress, high glucose per se does not up-regulate expression of the enzymes
      constituting the polyol pathway in Schwann cells. The RT-PCR system developed in
      this study may be a useful tool in ascertaining the relative contributions of AR
      and SDH to the metabolic derangements leading to diabetic complications.

PMID- 11245929
TI  - Hippocampal neurons of mice deficient in DNA-dependent protein kinase exhibit
      increased vulnerability to DNA damage, oxidative stress and excitotoxicity.
AB  - DNA damage has been documented in neurodegenerative conditions ranging from
      Alzheimer's disease to stroke. DNA-dependent protein kinase (DNA-PK) is involved
      in V(D)J recombination and DNA double strand break repair, and may play a role in
      cell death induced by DNA damage. We now report that cultured hippocampal neurons
      from severe combined immunodeficient (scid) mice which lack DNA-PK activity are
      hypersensitive to apoptosis induced by exposure to topoisomerase inhibitors,
      amyloid beta peptide (A beta) and glutamate. A similar increased vulnerability of
      hippocampal CA1 and CA3 neurons was observed in adult scid mice after kainate
      induced seizures. Our results suggest that DNA-PK activity is important for
      neuron survival under conditions that may occur in neurological disorders.

PMID- 11245930
TI  - The R100Q mutation of the GABA(A) alpha(6) receptor subunit may contribute to
      voluntary aversion to ethanol in the sNP rat line.
AB  - We have investigated the GABA(A) alpha(6) subunit molecular composition in two
      rat lines selectively bred for high or low ethanol preference and consumption,
      namely Sardinian alcohol-preferring (sP) and Sardinian non-alcohol-preferring
      (sNP) rats, which have been bred at the University of Cagliari, Italy, since
      1981. A total of 27 sP, 22 sNP and 25 control rats belonging to five other
      different strains, were studied by direct sequencing and amplification refractory
      mutation system analysis. Among the sNPs, only one was found to be normal, 11
      heterozygotes, and 10 homozygotes for the G-->A substitution in codon 100, the
      same R100Q point mutation previously described in Alcohol Non Tolerant rats,
      while no other animal showed any mutated allele. Pharmacological studies have
      extensively demonstrated that this substitution in the mature peptide changes the
      benzodiazepine-insensitive receptor to a sensitive one. In order to test the
      functional significance of this mutation in native cerebellar GABA(A) receptors,
      selective breeding from Q/R rats was employed to obtain a sufficient number of
      R/R homozygotes. Xenopus laevis oocytes were then injected with cerebellar
      synaptosomes extracted from Q/Q, R/Q and R/R sNP rats. Consistently, utilizing
      the two-electrode voltage-clamp technique, GABA-evoked currents mediated by
      GABA(A) receptors containing the mutated alpha(6) subunit were potentiated by
      diazepam with about a two-fold increased potency, as compared to receptors
      containing the wild-type, benzodiazepine-insensitive alpha(6) subunit. Our data
      show for the first time that a mutated GABA(A) alpha(6) receptor subunit
      segregates in a rat line which voluntarily avoids alcohol consumption, and
      further support a possible involvement of the GABA(A) receptor containing a
      mutated alpha(6) subunit in the genetic predisposition to alcohol preference.

PMID- 11245932
TI  - Herbivore host choice and optimal bad motherhood.
AB  - When theory predicts which phenotypes are well adapted to a given environment,
      the data do not always match the predictions. Host-plant selection by herbivorous
      insects is one such example. Herbivorous insects often appear to make poor
      choices about where their offspring should develop. New evidence presented by
      Scheirs et al. suggests that adult insects can choose oviposition sites that
      enhance their own long-term fitness at the expense of their individual offspring.
      This suggests that herbivorous insects might be genuinely bad mothers, that host
      choice is nonetheless adaptive, and that theory needs to incorporate new
      assumptions about host effects on adult performance.

PMID- 11245931
TI  - Dopamine D(1) receptor expression in human basal ganglia and changes in
      Parkinson's disease.
AB  - The expression of the human dopamine D(1) receptor was examined by reverse
      transcription polymerase chain reaction (RT-PCR) and radioligand binding using
      [(3)H]-SCH23390 in post-mortem brain tissue that was obtained from normal
      subjects and patients dying with Parkinson's disease who were receiving treatment
      with dopaminergic drugs. D(1) receptor mRNA and specific [(3)H]-SCH23390 binding
      sites were found in both striatal (nucleus accumbens, caudate nucleus and
      putamen) and extrastriatal (globus pallidus and substantia nigra) brain regions.
      In parkinsonian brain, D(1) receptor mRNA was increased in the nucleus accumbens,
      while a decrease was detected in the substantia nigra pars compacta. No change in
      D(1) mRNA levels was found in the other brain areas examined. An increase in the
      density of specific [(3)H]-SCH23390 binding sites was found in the anterior
      putamen and a decrease in the external segment of the globus pallidus, no changes
      were detected elsewhere. This study demonstrates that regulation of D(1) receptor
      expression in the brain of patients dying with Parkinson's disease that were
      treated with L-DOPA is confined to small alterations in restricted brain regions.

PMID- 11245933
TI  - Doubly duped males: the sweet and sour of the orchid's bouquet.
AB  - Flowers of the orchid genus Ophrys resemble female insects, and thereby sexually
      deceive, attract and are pollinated by male insects. Floral bouquet is thought to
      play a major role in this sexual mimicry, although the search for functional
      odour components has been something of a chemical ecologist's Holy Grail. Two new
      papers unravel the exquisite intricacy of the chemical deception by the orchid.

PMID- 11245935
TI  - An evolutionary slant on species-area curves.

PMID- 11245934
TI  - Mediterranean marine protected areas.
AB  - A collection of five recent papers assesses the role and effectiveness of marine
      protected areas (MPAs) in the Mediterranean. The papers provide a broad
      perspective of MPAs and include social, economic, cultural, biological and
      statistical components.

PMID- 11245937
TI  - Infidelity as a transaction between social mates.

PMID- 11245936
TI  - Skink skirmishes: why do owners win?

PMID- 11245938
TI  - Toxic nectar: one man's meat is another man's poison.

PMID- 11245939
TI  - Consequences of EU expansion for farmland birds in eastern Europe.

PMID- 11245940
TI  - The evolution of social behavior in microorganisms.
AB  - Recent studies of microorganisms have revealed diverse complex social behaviors,
      including cooperation in foraging, building, reproducing, dispersing and
      communicating. These microorganisms should provide novel, tractable systems for
      the analysis of social evolution. The application of evolutionary and ecological
      theory to understanding their behavior will aid in developing better means to
      control the many pathogenic bacteria that use social interactions to affect
      humans.

PMID- 11245941
TI  - Family values: group dynamics and social control of reproduction in African mole
      rats.
AB  - To exploit ecological niches where constraints have favoured selection for group
      living and cooperation, both vertebrates and invertebrates have evolved elaborate
      social systems. In mammals, numerous divergent taxa have converged at similar
      solutions to these ecological challenges (such as food distribution and predator
      avoidance), culminating in the social insect-like behaviour of the naked mole
      rat. Characteristically, breeding is partitioned unequally in such groups,
      resulting in a 'reproductive skew'. New research linking studies of physiology,
      behaviour and molecular ecology in African mole-rats is helping us to elucidate
      why different proximate mechanisms that control groups of cooperative breeders
      might have evolved.

PMID- 11245942
TI  - Functional ecology and palaeolimnology: using cladoceran remains to reconstruct
      anthropogenic impact.
AB  - The field of lake palaeoecology has undergone significant changes. Powerful
      quantitative techniques have been developed to investigate anthropogenic impacts
      on lakes. Inclusion of zooplankton and benthic chydorid cladocerans has provided
      previously unavailable information on the historical development of planktivorous
      fish populations, submerged macrophytes and lake production, and has been used to
      document exotic species introductions, rapid genetic evolution and human
      disturbance of lakes. In particular, new techniques now allow a more complete
      evaluation of changes in past and present trophic structure to be made, and
      provide insights on the rapid evolutionary responses of aquatic invertebrate
      communities to anthropogenic perturbation of lakes.

PMID- 11245943
TI  - Progress in invasion biology: predicting invaders.
AB  - Predicting which species are probable invaders has been a long-standing goal of
      ecologists, but only recently have quantitative methods been used to achieve such
      a goal. Although restricted to few taxa, these studies reveal clear relationships
      between the characteristics of releases and the species involved, and the
      successful establishment and spread of invaders. For example, the probability of
      bird establishment increases with the number of individuals released and the
      number of release events. Also, the probability of plant invasiveness increases
      if the species has a history of invasion and reproduces vegetatively. These
      promising quantitative approaches should be more widely applied to allow us to
      predict patterns of invading species more successfully.

PMID- 11245944
TI  - Species coexistence in temperate, mixed deciduous forests.
AB  - The response of tree life-history traits to community profiles (horizontal and
      vertical heterogeneity, disturbances and biotic interactions) determines
      community assembly rules, which are currently a hot issue in community ecology.
      Important mechanisms of coexistence differ throughout the developing stages of
      tree life history. Many processes of niche partitioning and tradeoffs that
      potentially enable tree coexistence have been reported to be present in temperate
      forests, although some of these life-history traits are either correlated with
      each other or are not independent. Not all of the proposed mechanisms explain
      coexistence equally well; some could predominate in determining the community
      organization of forest communities. Population studies need to concentrate more
      on the component species of a target community to detect the ecological assembly
      rule. These approaches can also address how chance factors contribute to the
      composition of temperate tree communities, which might be less dependent on
      chance than are tropical ones.

PMID- 11245945
TI  - Corrigendum.

PMID- 11245946
TI  - Erratum.

PMID- 11245965
TI  - Introduction to special issue on substance abuse and the immune system.

PMID- 11245966
TI  - Substance abuse and the immune system.

PMID- 11245967
TI  - Opioids, opioid receptors, and the immune response.
AB  - It is now clear that opioid receptors participate in the function of the cells of
      the immune system, and evidence suggests that opioids modulate both innate and
      acquired immune responses. We review literature here which establishes that mu-,
      kappa-, and delta-opioid compounds alter resistance to a variety of infectious
      agents, including the Human Immunodeficiency Virus (HIV). The nature of the
      immunomodulatory activity of the opioids has been the subject of a great deal of
      research over the last ten years. There is increasing evidence that effects of
      opioids on the immune response are mediated at several levels. Modulation of the
      inflammatory response appears to be a target of these compounds, including
      effects on phagocytic activity, as well as the response of cells to various
      chemoattractant molecules. Moreover, findings from several laboratories have
      demonstrated the impact of opioid treatment on antibody responses, and the
      molecular basis for this effect is likely due, at least in part, to the
      modulation of both cytokine and cytokine receptor expression. Future research
      should provide a clearer understanding of the cellular and molecular targets of
      opioid action within the immune system.

PMID- 11245968
TI  - Partial characterization and tissue distribution of the feline mu opiate
      receptor.
AB  - Heroin abuse is a common route of acquiring HIV-1 infection. However, the effects
      of opiates on lentivirus disease progression are not well understood. Feline
      immunodeficiency virus is recognized as a good animal model for HIV-1, but
      characterization of the opiate receptor system in cats is lacking. Here we report
      the partial sequencing of the feline mu opiate receptor (MOR) and demonstrate a
      homology of 92 and 93% to the published human MOR sequences. Additionally, MOR
      transcripts were detected in the feline brain and tonsil but not in the spleen.
      Also, specific receptor ligand interactions were observed using microphysiometry.

PMID- 11245969
TI  - The morphine-binding site on human activated T-cells is not related to the mu
      opioid receptor.
AB  - Mitogen activation of human T-lymphocytes induces a morphine-binding site.
      Morphine binding is displaceable by beta-endorphin (1--31) and (--)-naloxone but
      not DAMGO. This site is not stereoselective for (--)-morphine. T-lymphocytes,
      expressing this binding site, were assayed by reverse-transcription polymerase
      chain reaction (RT-PCR) for expression of hMOR-1 mRNA. Several primer sets were
      used and each assay compared with cells known to express human or mouse MOR-1
      mRNA. Neither hMOR-1 nor any homologous receptor was detected in human T
      lymphocytes. Therefore, the morphine-binding site on mitogen-activated T
      lymphocytes is unlikely to be closely related to hMOR-1.

PMID- 11245970
TI  - Reversal of acute effects of high dose morphine on lymphocyte activity by
      chlorisondamine.
AB  - To explore the mechanisms mediating the effects of acute morphine on the immune
      system, effects of ganglionic blockade with chlorisondamine on acute high dose
      morphine-induced alterations in blood lymphocyte proliferation, white blood cell
      counts, spleen lymphocyte proliferation and splenic natural killer (NK) cell
      cytolytic activity were examined in male Sprague--Dawley rats. Two hours after
      morphine (30 mg/kg, s.c.) administration, blood lymphocyte proliferation (ConA)
      was decreased 85%; this effect was antagonized by chlorisondamine (5 mg/kg,
      i.p.). Notably, however, such morphine exposure did not significantly decrease
      splenic lymphocyte proliferation, although depression of NK cell activity was
      also evident and appeared to be chlorisondamine-sensitive. Immune effects of
      morphine 1 h after treatment were somewhat different. In this case, blood
      lymphocyte proliferation decreased and plasma levels of corticosterone increased,
      with ED(50) values of 2.2 and 7.8 mg/kg, respectively. Splenic lymphocyte
      proliferation and NK activity were also significantly depressed in the 1-h
      exposure paradigm, but only after administration of 30 mg/kg morphine. These
      results indicate that chlorisondamine blocks the effects of relatively high doses
      of morphine on blood lymphocyte activity and indicate that blood lymphocyte
      proliferation is more sensitive to effects of acute morphine exposure than
      splenic lymphocyte proliferation, NK cell cytolytic activity and activation of
      the HPA axis.

PMID- 11245972
TI  - Gene delivery and gene therapy with herpes simplex virus-based vectors.
AB  - The development of efficient means of delivery genes in vivo is essential both
      for testing gene function in the intact animal and for human gene therapy
      procedures. A number of viral and non-viral gene delivery methods have been
      developed for this purpose. Of those herpes simplex virus (HSV)-based vectors
      have particular advantages for gene delivery to the nervous system including
      their ability to infect non-dividing neurones and establish asymptomatic latent
      infections. Moreover, considerable progress has been made, firstly, in disabling
      HSV vectors so as to prevent the damaging effects of wild type virus and
      secondly, to ensure long-term expression of the inserted transgene(s). These
      vectors thus offer a valuable tool for testing gene function in neuronal cells in
      vivo and may ultimately be safe enough for use in human gene therapy procedures.

PMID- 11245971
TI  - U50488 inhibits HIV-1 expression in acutely infected monocyte-derived
      macrophages.
AB  - Opioids may play an immunomodulatory role in the pathogenesis of human
      immunodeficiency virus-1 (HIV-1) infection. Recently, synthetic kappa-opioid
      receptor (KOR) ligands have been found to have anti-human immunodeficiency virus
      type 1 activity in acutely infected brain macrophages. In the present study, we
      investigated whether the selective KOR ligand U50488 would exert such an anti-HIV
      1 effect in acutely infected blood monocyte-derived macrophages (MDM). Treatment
      of acutely infected MDM with U50488 induced a concentration-dependent inhibition
      of HIV-1 expression. The dose--response relationship of U50488 was U-shaped with
      a peak effect observed at 10(-13) M, which was evident at both 7 and 14 days post
      infection. The KOR antagonist nor-binaltorphimine blocked the anti-HIV-1 effect
      of U50488 by 73%, indicating involvement of a KOR-mediated mechanism. Also,
      expression of KOR mRNA and binding activity with a fluorescence-labeled KOR
      ligand supported the existence of KOR on MDM. Antibodies to the beta-chemokine,
      RANTES (regulated on activation normal T-cell expressed and secreted), but not to
      various other cytokines, blocked U50488 inhibition by 56% suggesting that the
      anti-HIV-1 effect of U50488 involved, in part, the production of RANTES by MDM.
      Taken together, these in vitro findings support the anti-HIV-1 property of
      U50488, and suggest that KOR ligands may have therapeutic potential for treating
      patients with acquired immunodeficiency syndrome.

PMID- 11245973
TI  - Construction of a PAC vector system for the propagation of genomic DNA in
      bacterial and mammalian cells and subsequent generation of nested deletions in
      individual library members.
AB  - The BAC and PAC cloning systems allow investigators to propagate large genomic
      DNA fragments up to 300 kb in size in E. colicells. We describe a new PAC shuttle
      vector that can be propagated in both bacterial and human cells. Specifically,
      the P1 cloning vector pAd10sacBII was modified by the insertion of a puromycin
      resistance gene (pac), the Epstein-Barr Virus (EBV) latent replication origin
      oriP,and the EBV EBNA1 gene. Transfection studies in HEK 293 cells demonstrated
      that the modified vector was stably maintained as an episome for at least 30
      generations. And since pJCPAC-Mam1 contains a loxP site, genomic DNA cloned into
      this vector can be subjected to loxP-Cre -mediated deletion events. The
      transposon vector pTnPGKpuro/loxP was modified to make this system amenable to
      propagation in human cells by inserting pac, oriP, and EBNA1 elements into the
      vector (Chatterjee, P.K., Coren, J.C., 1997. Isolating large nested deletions in
      PACs and BACs by in vivo selection of P1 headful-packaged products of Cre
      catalyzed recombination between the loxP site in PAC and BAC and one introduced
      in transposition. NAR 25, 2205-2212.). pTnPGKpuro/loxP-EBV was then used to
      generate deletions in an individual library member to demonstrate that all of the
      deletions still contain the required eukaryotic elements and that they were
      nested. All library members constructed in pJCPAC-Mam1 can be directly
      transformed into human cells to assess function. And the deletion technology can
      be used to aid in delineating the boundaries of genes and other cis-acting
      elements.

PMID- 11245974
TI  - Characterization and promoter analysis of the mouse gene for transcription factor
      Sp4.
AB  - Transcription factor Sp4 is a member of the Sp1 family. It functions differently
      from other members of this family, such as Sp1 and Sp3, and the gene for Sp4 is
      transcribed in a tissue-specific manner. Recent studies in mice suggest that Sp4
      might play an important role in growth, viability, and male fertility. We report
      here the isolation and characterization of the gene for Sp4 from a mouse genomic
      library. The mouse gene for Sp4 was about 80 kb in length and it consisted of six
      exons and five introns. The promoter was found in a CpG island and had a high G+C
      content. The proximal promoter contained multiple putative binding sites for the
      transcription factors Sp1 and MAZ but lacked a consensus TATA box. Multiple sites
      for the initiation of transcription were mapped in a GC-rich region from 286 bp
      to 211 bp upstream of the ATG triplet at the site of initiation of translation,
      and all of the sites were either C or G. Transfection experiments and deletion
      analysis allowed us to localize the promoter to a region that was no more than 93
      bp upstream from the first site of initiation of transcription. We also found
      that ectopic expression of Sp1 and of MAZ, but not of Sp3, suppressed expression
      of the Sp4 promoter in a dose-dependent manner.

PMID- 11245975
TI  - The genomic basis of K(V)3.4 potassium channel mRNA diversity in mice.
AB  - K(V)3.4 belongs to the shaw subfamily of shaker-type potassium channels. It
      conducts fast inactivating, high threshold currents in the central nervous system
      and in fast-twitch skeletal muscle fibers. The corresponding mouse gene, Kcnc4,
      consists of five exons spanning a region of 20 kb. Approximately 700 bp of
      regulatory sequence were delineated. It is GC-rich and lacks typical TATA and
      CAAT motifs. Instead, seven Sp-1 and three E-box elements define putative
      regulatory sequences. The mouse K(V)3.4 mRNA has a size of 3639 bp, 1120 bp of
      which are 3' untranslated region. A transcript initiated from an alternative 5'
      exon was identified by RACE and verified by genomic analysis. This isoform,
      designated K(V)3.4d, is predominantly expressed in skeletal muscle and probably
      results from alternative promoter usage. It encodes a channel protein with a
      novel N-terminal cytoplasmic domain. It lacks the conserved sequence motifs
      encoding the shaw-type tetramerization domain and the 'ball' peptide, which
      confers fast inactivation properties. Another splice variant, K(V)3.4c, is
      derived by exon skipping in the C-terminal region and is expressed at similar
      levels in brain and muscle. These data demonstrate that differential splicing and
      alternative transcription start sites are utilised to generate a set of K(V)3.4
      variants in skeletal muscle and brain, presumably involved in the regulation of
      excitability.

PMID- 11245976
TI  - Characterization and tissue expression of a novel human gene npdc1.
AB  - We report the molecular characterization of a novel human homologue of mouse
      npdc1 (neural proliferation, differentiation and control, 1) gene, designated
      human npdc1 (hnpdc1). hnpdc1 was identified by large-scale sequencing of fetal
      liver cDNA libraries and the full-length cDNA was obtained by PCR amplification.
      The hnpdc1 gene, which contains nine exons, was mapped to human chromosome 15. It
      encodes a polypeptide of 325 amino acids, which shows high homology (77%
      identity) to the mouse NPDC1. Sequence analysis has shown that hNPDC1 protein
      contains a putative signal peptide of 34 amino acids, a transmembrane segment,
      and a typical bipartite nuclear localization signal. Northern blot and dot blot
      hybridization indicates that, just like mnpdc1, hnpdc1 mRNA is strongly expressed
      in adult brain (especially in hippocampus, frontal lobe and temporal lobe) and
      about 1.82-fold higher in adult brain than that in fetal brain. Unlike mnpdc1,
      however, hnpdc1 contains two transcripts instead of only one (1.5 kb), and has
      high expression levels in prostate, pituitary gland, and mammary glands. These
      results support that hNPDC1 plays a role in the control of neural cell
      proliferation and differentiation, and suggest that it may be involved in the
      development of several secretion glands.

PMID- 11245977
TI  - The lens protein alpha-B-crystallin of the blind subterranean mole-rat: high
      homology with sighted mammals.
AB  - Blind subterranean mole rats, Spalax ehrenbergi, retain a subcutaneous,
      degenerated eye, which is visually non-functional but which does function in
      circadian entrainment. Crystallins, members of the small heat shock protein
      family, constitute approximately 90% of the water-soluble proteins of the
      transparent eye lens and are crucial for its optical properties, but they are
      also expressed in other tissues. In our attempt to understand the role of the eye
      in the blind mole-rat, we now describe the cloning, sequencing, and expression of
      the cDNA of alpha-B-Crystallin from two species of Spalax (S. galili and S.
      Judaei, with diploid chromosome numbers 2n=52 and 60, respectively). Spalax alpha
      B-Crystallin is highly conserved. It is expressed in many tissues of Spalax,
      among them Spalax eye. The sequence of the cDNA of alpha-B-Crystallin in the eye
      and in the heart of Spalax is identical. Further studies are essential to clarify
      the role of this gene in the lens of an atrophied eye of a visually blind mammal.

PMID- 11245979
TI  - Gulliver, a long terminal repeat retrotransposon from the genome of the oriental
      blood fluke Schistosoma japonicum.
AB  - We characterized the consensus sequence and structure of a long terminal repeat
      (LTR) retrotransposon from the genome of the human blood fluke, Schistosoma
      japonicum, and have named this element, Gulliver. The full length, consensus
      Gulliver LTR retrotransposon was 4788 bp, and it was flanked at its 5'- and 3'
      ends by LTRs of 259 bp. Each LTR included RNA polymerase II promoter sequences, a
      CAAT signal and a TATA box. Gulliver exhibited features characteristic of a
      functional LTR retrotransposon including two read through (termination) ORFs
      encoding retroviral gag and pol proteins of 312 and 1071 amino acid residues,
      respectively. The gag ORF encoded motifs conserved in nucleic acid binding
      proteins, while the pol ORF encoded conserved domains of aspartic protease,
      reverse transcriptase (RT), RNaseH and integrase, in that order, a pol pattern
      conserved in the gypsy lineage of LTR retrotransposons. Whereas the sequence and
      structure of Gulliver was similar to that of gypsy, phylogenetic analysis
      revealed that Gulliver did not group particularly closely with the gypsy family.
      Rather, its closest relatives were a LTR retrotransposon from Caenorhabditis
      elegans, mag from Bombyx mori and, to a lesser extent, easel from the salmon
      Oncorhynchus keta. Dot blot hybridizations indicated that Gulliver was present at
      between 100 and several thousand copies in the S. japonicum genome, and Southern
      hybridization analysis suggested its probable presence in the genome of
      Schistosoma mansoni. Transcripts encoding the RT domain of Gulliver were detected
      by RT-PCR in larval and adult stages of S. japonicum, indicating that (at least)
      the RT domain of Gulliver is transcribed. This is the first report of the
      sequence and structure of an LTR retrotransposon from any schistosome or indeed
      from any species belonging to the phylum Platyhelminthes.

PMID- 11245978
TI  - Active genes in junk DNA? Characterization of DUX genes embedded within 3.3 kb
      repeated elements.
AB  - The human genome contains hundreds of repeats of the 3.3 kb family in regions
      associated with heterochromatin. We have previously isolated a 3.3 kb-like cDNA
      encoding a double homeodomain protein (DUX1). Demonstration that the protein was
      expressed in human rhabdomyosarcoma TE671 cells, and characterization of a
      homologous promoter suggested that functional DUX genes might be present in 3.3
      kb elements. In the present study, we describe two nearly identical 3.3 kb/DUX
      genes derived from PAC 137F16 (DUX3), and TE671 genomic DNA (DUX5), both mapping
      to all the acrocentric chromosomes. Their promoters harbor a GC and a TATAA box,
      and the open reading frame of the intronless structural part encodes two DUX
      proteins differing by alternative translation initiation. The shorter protein of
      the DUX5 gene is identical to DUX1. Using a protein truncation test, we could
      show that these two proteins are encoded by total RNA, but not by poly (A)(+)
      RNA, from different human tissues and cell lines. Our results indicate that
      active genes of unusual structure are present in chromosome regions characterized
      by large amounts of heterochromatic repetitive DNA.

PMID- 11245980
TI  - Cloning a calcium channel alpha2delta-3 subunit gene from a putative tumor
      suppressor gene region at chromosome 3p21.1 in conventional renal cell carcinoma.
AB  - We have identified loss of heterozygosity (LOH) of approx. 1 cM region around
      locus D3S1289 at chromosome 3p21.1 in a conventional renal cell carcinoma (RCC).
      During construction of a YAC/BAC contig for this region and shotgun sequencing of
      BACs 277p5, 55m24 and 428i24, we detected four new microsatellites. We narrowed
      down the target region by analysing these new loci to less than 100 kb within the
      BAC 55m24 and subsequently cloned a human calcium channel alpha2delta-3 subunit
      gene. This gene is widely expressed in fetal tissues and different types of adult
      tumors. The exons of the alpha2delta-3 subunit gene are distributed along approx.
      500 kb DNA sequences. As the LOH involved exclusively intronic sequences and
      sequencing the entire coding region did not reveal any mutation, the alpha2delta
      3 subunit gene is probably not a tumor suppressor gene.

PMID- 11245981
TI  - Analysis of the pobA and pobR genes controlling expression of p-hydroxybenzoate
      hydroxylase in Azotobacter chroococcum.
AB  - We report the cloning and analysis of a gene and its cognate regulatory element
      from a member of the Azotobacteriaceae which are involved in the breakdown of an
      aromatic compound. The genes from Azotobacter chroococcum encoding p
      hydroxybenzoate hydroxylase (pobA) and its regulatory protein (pobR) were cloned
      from a genomic library and sequenced. Sequence analysis of pobA revealed homology
      with other bacterial p-hydroxybenzoate hydroxylase enzymes. Residues essential to
      the structure and function of the enzyme have been conserved. The pobR gene
      encodes a DNA binding regulatory protein with similarity to proteins from the
      AraC/XylS family of transcriptional activators. A fragment containing both pobA
      and pobR was cloned into pUC19 and p-hydroxybenzoate hydroxylase activity was
      induced in Escherichia coli by the addition of p-hydroxybenzoate. A frame-shift
      mutation introduced into the pobR gene prevented expression of p-hydroxybenzoate
      hydroxylase, indicating that PobR is the protein required for transcription of
      pobA. Interestingly, A. chroococcum PobR has no homology to the PobR protein that
      is the transcriptional activator of pobA in Acinetobacter strain ADP1, a protein
      that is homologous to the IclR family of transcriptional regulators. However,
      PobR from A. chroococcum is homologous to several other proteins, suggesting that
      these proteins will also function as transcriptional activators of pobA.

PMID- 11245982
TI  - Identification of a new multigene four-transmembrane family (MS4A) related to
      CD20, HTm4 and beta subunit of the high-affinity IgE receptor.
AB  - We report here the cloning of eight new cDNAs that encode a family of proteins
      related to the B-cell-specific antigen CD20, a hematopoietic-cell-specific
      protein HTm4, and high affinity IgE receptor beta chain (FcvarepsilonRIbeta).
      They include four clones from human, and another four clones from mouse. They
      share similar structure (four transmembrane domains) with amino acid identities
      of 25-40%. Therefore, they represent distinct genes and comprise a gene
      superfamily. This superfamily is now named membrane-spanning four-domains,
      subfamily A (the approved symbol is MS4A) to distinguish them from tetraspanins
      with similar structure. The highest homologies among these proteins are found in
      the transmembrane domains, especially in the first and second transmembrane
      domains, and conserved residues are also recognized in the inter-transmembrane
      domains. In northern blot, they were mostly expressed in lymphoid tissues: thymus
      and spleen. However, some were expressed in nonlymphoid tissues including brain,
      heart, kidney, liver, testis, lung, GI tracts, and pancreas. They may represent
      proteins functioning either directly as ligand-gated ion channels or as essential
      components of such channels. The identification of this relatively large gene
      family in various tissues will allow the further elucidation of physiological
      significance of this gene family, that is currently unclear.

PMID- 11245984
TI  - The carcinoembryonic antigen (CEA) gene family in non-human primates.
AB  - Carcinoembryonic antigen (CEA) is a tumor marker of wide clinical use though its
      function remains unknown. The CEA counterpart and some related macromolecules
      cannot be demonstrated in mice, thus prohibiting studies of CEA function by gene
      disruption strategies. In an attempt to find a relevant animal model for
      functional studies of CEA we have investigated the occurrence of CEA subgroup
      members in baboon and African green monkey at the genomic and mRNA levels. The
      investigation was focused on the characteristic immunoglobulin-variable region
      like (IgV-like) N-terminal domain of the family members. Based on N-domain
      sequences 3 and 4 different CEA subgroup genes, respectively, were identified.
      One sequence in each monkey species corresponded to human CEACAM8, while it was
      not possible to assign an obvious human counterpart for the other N-domain
      sequences. However, studies of cDNAs from African green monkey COS-1 cells
      identified one of the sequences as CEACAM1. Expression of CEACAM1 mRNA and
      protein was upregulated by IFNgamma as has previously been demonstrated for human
      CEACAM1. Presence of GPI-linked CEA subgroup members in African green monkey was
      suggested by sequencing. Both monkey species would thus seem suitable for
      functional studies of selected CEA subgroup members.

PMID- 11245983
TI  - The human gastrin-releasing peptide receptor gene structure, its tissue
      expression and promoter.
AB  - The human gastrin-releasing peptide receptor (hGRP-R) is aberrantly expressed in
      cancers of the colon, lung and prostate and mediates signals of cellular
      proliferation. However, the underlying mechanisms of aberrant and/or activation
      of hGRP-R expression are unknown. Therefore, a genomic clone is identified, the
      hGRP-R gene is characterized, and the hGRP-R promoter is defined. The protein
      coding region is divided into three exons and exon/intron splice sites occur in
      the proximal 2nd and distal 3rd intracellular loops of the receptor molecule. The
      hGRP-R locus extends over more than 27 kb and is assigned to the chromosomal band
      Xp22 by fluorescence in situ hybridization. With primer extension experiments, we
      demonstrate two major transcription start sites in gastrointestinal and breast
      cancer cells, located 43 and 36 bp downstream of a TTTAAA motif which is
      identified 407 to 402 bp upstream of the ATG start codon. The hGRP-R is found
      most abundantly expressed in the normal human pancreas, where four gene-specific
      transcripts can be detected by Northern blot analysis, whereas only two
      transcripts are detected in the human stomach and, very weakly, in the adrenal
      cortex and the brain. In contrast, the human GRP-R is not expressed in the normal
      human colon, lung, and prostate. Steady state hGRP-R mRNA can also be detected in
      some cultured cells from breast, lung, and duodenal cancer. Robust hGRP-R
      promoter activity is demonstrated in a duodenal carcinoma cell line that natively
      expresses the functional hGRP-R. Truncation studies suggest a CRE motif, located
      112 bp upstream of the major transcription start site, is required to confer
      basal hGRP-R promoter activity in duodenal cancer cells. These studies provide
      the necessary data to further elucidate molecular mechanisms of aberrant hGRP-R
      expression in human cancers.

PMID- 11245985
TI  - Genomic structures of SCN2A and SCN3A - candidate genes for deafness at the
      DFNA16 locus.
AB  - DFNA16 is a form of autosomal dominant non-syndromic hearing loss (ADNSHL)
      characterized by fluctuating progressive hearing impairment. Earlier, we mapped
      the deafness-causing gene to chromosome 2q23-24.3. In this paper, we describe
      fine mapping results using additional markers tightly linked to the DFNA16
      candidate region. Critical recombinants at markers D2S354 and D2S124 define a 3.5
      cM interval that contains the DFNA16 gene. Positional candidate genes include two
      members of the voltage-gated sodium channel family, the type 2 alpha subunit
      (SCN2A) and the type 3 alpha subunit (SCN3A). After showing that SCN2A is
      expressed in human fetal cochlea, we determined its genomic structure to
      facilitate mutation screening in our DFNA16 kindred. We also determined the
      genomic structure of SCN3A. These two genes are oriented head-to-head, with their
      5' ends separated by approximately 40 kb; their homology is 82% at the nucleotide
      level, and 85% for identities and 90% for positives at the amino acid level. They
      share similar genomic structures and have alternative splice isoforms that are
      developmentally regulated and highly conserved between species. Although no
      DFNA16-causing mutations were found in either gene, haplotype analysis with
      polymorphic markers in SCN2A introns further narrowed the candidate gene interval
      to the region flanked by D2S354 and STS SHGC-82894.

PMID- 11245986
TI  - A novel growth-related nuclear protein binds and inhibits rat aldolase B gene
      promoter.
AB  - The promoter of the rat aldolase B (AldB) gene that confers liver-specific
      transcription has an additional role. It functions in vivo as an origin region of
      DNA replication in the cells in which the gene is repressed (Zhao, Y., Tsutsumi,
      R., Yamaki, M., Nagatsuka, N., Ejiri, S., Tsutsumi, K., 1994. Initiation zone of
      DNA replication at the rat aldolase B locus encompasses transcription promoter
      region. Nucleic Acids Res. 22, 5385-5390). This promoter/origin region has
      multiple protein-binding sites and, thus, binding of a particular set of protein
      factors in AldB-expressing or non-expressing cells seems to correlate with
      functional switch of this promoter/origin region. In the present study, we
      characterized two closely related proteins, termed AlF-C1 and AlF-C2, which are
      assumed to be involved in repression of the AldB gene. These two proteins share
      an identical amino acid sequence except for a 47-residue-insertion in AlF-C1, and
      are members of a gene family including heterogeneous nuclear ribonucleoprotein
      (hnRNP) and CCAAT-binding factor subunit A (CBF-A) genes. Bacterially expressed
      AlF-C1 can bind sequence-specifically to the AldB gene promoter, whereas AlF-C2
      can only weakly. Transfection experiments using mammalian expression vectors
      showed that AlF-C1 down-regulates the AldB gene promoter in rat hepatoma cells,
      while AlF-C2 had no or little effect. Expressions of mRNAs encoding these two
      proteins are enriched in fetal livers and in regenerating livers. These results
      implied that AlF-C1 and/or C2 is involved in growth-regulated repression of the
      AldB gene.

PMID- 11245987
TI  - The human ubiquitous 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene
      (PFKFB3): promoter characterization and genomic structure.
AB  - A DNA fragment containing 1.5 kb of the 5'-flanking region of the human
      ubiquitous PFKFB3 gene, coding for 6-phosphofructo-2-kinase/fructose-2,6
      bisphosphatase, was cloned and its promoter activity was examined. The 5'
      flanking region contains a TATA box-like and GC-rich sequences, yielding several
      potential Specific protein (Sp-1) and activator protein (AP)-2 binding sites.
      Putative regulatory motifs for E-box, nuclear factor (NF)-1 and progesterone
      response element were also found by computer assisted analysis. Transient
      expression assays of truncated promoter-reporter constructs in HeLa cells showed
      that this gene is induced by phorbol esters (PDB) and cyclic-AMP-dependent
      protein kinase signal activation. Furthermore, the genomic organization of the
      PFKFB3 gene is reported. This gene spans more than 26 kb containing at least 16
      exons that accounts for the two reported isoforms, inducible and ubiquitous,
      generated through alternative splicing of exon 15.

PMID- 11245988
TI  - Characterization of the 5' and 3' untranslated regions in murine mdm2 mRNAs.
AB  - The murine double minute 2 (mdm2) gene is essential for embryogenesis in mice
      that express the p53 tumor suppressor protein. Mdm2 levels must be regulated
      tightly because overexpression of mdm2 contributes to tumorigenesis. We
      investigated whether the 5' and 3' untranslated regions (UTRs) of murine mdm2
      affect the expression of MDM2 proteins. Induction of mdm2 expression by p53
      results in synthesis of an mdm2 mRNA with a short 5' UTR. The long 5' UTR
      increases internal initiation of translation of a minor MDM2 protein, p76(MDM2),
      without affecting the efficiency of translation of the full-length p90(MDM2). We
      discovered two alternative 3' untranslated regions in murine mdm2 mRNA expressed
      in the testis. The longer 3' UTR contains a consensus instability element, but
      mdm2 mRNAs containing the long and short 3' UTRs have comparable half-lives. The
      3' UTRs do not affect either initiation codon use or translation efficiency.
      Thus, the murine 5' UTR, but not the 3'UTR, influences the ratio of the two MDM2
      proteins but neither UTR affects MDM2 abundance significantly.

PMID- 11245989
TI  - cDNA cloning, mapping and expression of the mouse propionyl CoA carboxylase beta
      (pccb), the gene for human type II propionic acidaemia.
AB  - Propionyl CoA carboxylase (PCC) is a mitochondrial, biotin-dependent enzyme
      involved in the catabolism of amino acids, odd-chained fatty acids and other
      metabolites. PCC is composed of two equal subunits, alpha and beta, which are
      encoded by two separate genes at two distinct human loci. Mutations of either
      gene in humans results in propionic acidemia (PA). To identify the mouse cDNA for
      the propionyl CoA carboxylase beta-subunit (pccb), we have screened the mouse EST
      database using the human sequence. The murine mRNA transcript is approximately
      2.3 kb, nearly 500 bps larger than the human approximately 1.8 kb transcript. A
      PAC genomic DNA clone from the mouse was also isolated and used to generate
      probes and PCR primers for mapping the pccb locus in the mouse. Both the
      C57Bl/6JEi and Spret/Ei alleles for regions flanking the pccb gene were sequenced
      to identify RFLPs. The Jackson Laboratory BSS and BSB backcross panel DNAs were
      then analyzed using a DdeI polymorphism placing the pccb locus on mouse
      chromosome 9. Northern blots of adult tissue show that the pccb gene is broadly
      expressed in the mouse. The approximately 2.3 kb transcript is most abundantly
      expressed in the kidney, liver, small intestine and stomach tissues.

PMID- 11245990
TI  - Placental lesion multiplicity: risk factor for IUGR and neonatal cranial
      ultrasound abnormalities.
AB  - OBJECTIVE: To determine whether placental lesions are risk factors for neurologic
      morbidities in intrauterine growth restricted (IUGR) infants, we compared the
      incidence of cranial ultrasound (CUS) abnormalities and the number and type of
      placental lesions in IUGR cases and gestational age-matched appropriate for
      gestational age (AGA) controls. STUDY DESIGN: Retrospective case-control study of
      94 singleton IUGR and 145 AGA infants. Medical records, CUS reports, and
      placental histology were reviewed. Analyses included chi2, t-test, analysis of
      variance and logistic regressions to identify those variables significantly
      associated with IUGR and those associated with CUS abnormalities. RESULTS: The
      incidence of CUS abnormalities was 1.7-fold higher in IUGR cases (50%) than
      controls (29.7%) (p<0.05). A total placental lesion score of > or =3 was
      associated with an increased risk for IUGR (OR 14.18, 3.41-58.99; p<0.001) and
      increased risk for CUS abnormality (OR 12.571, 3.33-47.416; p<0.05). In a
      logistic regression model only > or =2 placental lesions, IUGR and gestational
      age <30 weeks were significant independent predictors of CUS abnormalities.
      CONCLUSIONS: The severity of placental abnormalities expressed as the cumulative
      number of placental lesions is a significant risk factor for IUGR and perinatal
      brain injury. These results suggest that abnormal uteroplacental or fetoplacental
      blood flow may adversely affect intrauterine growth and increase the risk for
      brain injury.

PMID- 11245991
TI  - Pulmonary surfactant protein A in sera for assessing neonatal lung maturation.
AB  - To examine whether surfactant protein A (SP-A) in postnatal serum can predict the
      development of respiratory distress syndrome (RDS), we analyzed the relationship
      between serum concentrations of SP-A and the risk of RDS using sera from neonates
      within 24 h after birth. A total of 104 blood samples including 23 samples from
      newborn infants with RDS were obtained. SP-A content in sera was measured with an
      enzyme-linked immunosorbent assay system consisting of a standard of native SP-A
      and two monoclonal antibodies against human SP-A. The level of serum SP-A
      increased with advancing gestation. Since the mean level of serum SP-A in
      patients with RDS (3.8 ng/ml) was significantly lower than those without RDS
      (12.0 ng/ml) (P<0.001), we calculated the diagnostic index values at various
      cutoff points and chose cutoff values to predict the risk of RDS. Maximum
      diagnostic value of 85% was obtained at a cutoff point of 3.8 ng/ml (sensitivity
      57% and specificity 93%). We also chose a cutoff value of 2.1 ng/ml for
      definitive diagnosis of RDS, and 8.3 ng/ml for exclusive diagnosis of RDS. The
      adjusted odds ratios of RDS was significantly elevated when SP-A concentration in
      serum was under the cutoff values. The presence of SP-A in cord blood serum was
      also confirmed by immunoblotting analysis. We emphasize the value of SP-A
      examination in cord blood or postnatal serum from infants who exhibited
      respiratory difficulties at birth. We believe that our results are consistent
      with the hypothesis that SP-A is a useful serum marker in predicting the
      development of RDS.

PMID- 11245992
TI  - Monitoring of early postnatal glucose homeostasis and cerebral function in
      newborn infants of diabetic mothers. A pilot study.
AB  - The aims of this pilot study were to evaluate a new technique in the monitoring
      of postnatal glucose homeostasis (microdialysis) and also to study possible
      associations between early postnatal hypoglycaemia and influences on cerebral
      function monitoring (CFM) in 12 newborn infants of diabetic mothers. In order to
      study the postnatal glucose homeostasis, frequent dialysate samples were obtained
      from a subcutaneous microdialysis catheter for measurements of glucose. In
      addition, we also received samples of dialysate lactate and glycerol. Dialysate
      glucose concentrations were correlated to capillary blood glucose levels,
      measured by a glucose oxidase method. The cerebral function monitor was applied
      postnatally and a registration was obtained continuously. Capillary blood glucose
      decreased initially, and seven newborns received intravenous glucose infusions
      due to glucose concentrations less than 2.2 mmol/l. Dialysate glucose
      concentrations were, on average, 0.4 mmol/l higher than corresponding
      concentrations in capillary blood. The correlation coefficient between the two
      measurements was 0.63 and the coefficient of variation was 19.2%. Dialysate
      lactate and glycerol levels increased significantly, with peak values 3-4 h
      postnatally. No significant overall influence of hypoglycaemia was detectable in
      the CFM tracing. We conclude that a relatively poor correlation was observed
      between glucose measurements in capillary samples and microdialysis. However,
      using the microdialysis technique saw indication of marked lipolysis and
      increased lactate production, which may be of importance for cerebral postnatal
      adaptation. The mild postnatal hypoglycaemia in infants of diabetic mothers does
      not seem to give visually detectable influences on CFM.

PMID- 11245993
TI  - HeatBalance, a computer program to determine optimum incubator air temperature
      and humidity. A comparison against nurse settings for infants less than 29 weeks
      gestation.
AB  - BACKGROUND: Very immature newborn infants need close control of their thermal
      environment. Decisions on incubator temperature and humidity settings can be
      difficult and available charts are not readily applicable to these babies. A
      computer program (HeatBalance) using basic principles to calculate heat gains and
      losses has been developed. The program recommends incubator temperature and
      humidity settings to keep babies in thermal balance. AIM: The aim of this study
      was to compare the effect of the program on temperature control of infants <29
      weeks gestation with that achieved by experienced nurses. METHOD: Twenty
      consecutive babies were studied over the first 5 days of life, all nursed in
      incubators using air mode control. The first 10 had temperature and humidity set
      by the nurses while the next 10 had incubator settings determined by the program.
      Nurses could alter the parameters if the babies were too hot or cold. Incubator
      temperature and humidity data along with central and peripheral temperatures from
      the babies were collected autonomicallly onto a cotside computer system. RESULTS:
      There were no differences between the groups in mean central temperatures or the
      periods of time the babies were either too hot (central temperature T(c)>37.5) or
      too cold (T(c)<36.5). In the control group, the nurses often altered incubator
      temperature because of changes in the infant's temperature on the monitors. On
      each day of the study, the nurses deviated from the HeatBalance recommendations
      between 11% and 22% of the time. CONCLUSIONS: The HeatBalance program and the
      nurses achieved similar results in temperature stability for these immature
      infants. Whichever method was used to determine the initial incubator settings,
      this study highlighted the importance of continuous monitoring of central and
      peripheral temperatures in these infants.

PMID- 11245994
TI  - International Child Care Practices Study: infant sleeping environment.
AB  - BACKGROUND: The International Child Care Practices Study (ICCPS) has collected
      descriptive data from 21 centres in 17 countries. In this report, data are
      presented on the infant sleeping environment with the main focus being sudden
      infant death syndrome (SIDS) risk factors (bedsharing and infant using a pillow)
      and protective factors (infant sharing a room with adult) that are not yet well
      established in the literature. METHODS: Using a standardised protocol, parents of
      infants were surveyed at birth by interview and at 3 months of age mainly by
      postal questionnaire. Centres were grouped according to geographic location. Also
      indicated was the level of SIDS awareness in the community, i.e. whether any
      campaigns or messages to "reduce the risks of SIDS" were available at the time of
      the survey. RESULTS: Birth interview data were available for 5488 individual
      families and 4656 (85%) returned questionnaires at 3 months. Rates of bedsharing
      varied considerably (2-88%) and it appeared to be more common in the samples with
      a lower awareness of SIDS, but not necessarily a high SIDS rate. Countries with
      higher rates of bedsharing appeared to have a greater proportion of infants
      bedsharing for a longer duration (>5 h). Rates of room sharing varied (58-100%)
      with some of the lowest rates noted in centres with a higher awareness of SIDS.
      Rates of pillow use ranged from 4% to 95%. CONCLUSIONS: It is likely that methods
      of bedsharing differ cross-culturally, and although further details were sought
      on different bedsharing practices, it was not possible to build up a composite
      picture of "typical" bedsharing practices in these different communities. These
      data highlight interesting patterns in child care in these diverse populations.
      Although these results should not be used to imply that any particular child care
      practice either increases or decreases the risk of SIDS, these findings should
      help to inject caution into the process of developing SIDS prevention campaigns
      for non-Western cultures.

PMID- 11245996
TI  - Estimating the testis volume during the fetal period using the stereological
      method.
AB  - The purpose of the present study is to assess the development of seminiferous
      tubule volume, stromal volume and total testis volume in the human fetal testis
      during the fetal period using the stereological method. In this study, we
      examined 90 testes of 45 human fetuses with no congenital anomalies and
      pathologies. They were aged between 12 and 40 weeks and localized between the
      scrotum and the abdomen. Total testis volume, seminiferous tubule volume, and
      stromal volume were estimated using Cavalier Principles. The weight and density
      of the testes were calculated as well. During the fetal period, the testes were
      firstly found on the right in the 27th week and on the left in the 32nd week in
      the scrotum. At the end of the third trimester and full term, the migration of
      the testes into scrotum was completed (98%). When the second trimester, third
      trimester and full term fetuses were compared, the differences between testis
      volumes were significant (p<0.001). The density of the testes between the groups
      was not significant (p>0.05). Testis parameters during the fetal period were not
      significantly (p>0.05) different between the right and left testes localization.
      The correlation between the fetal testis parameters was significant (p<0.001).
      Towards the end of the fetal period, the rate of seminiferous tubule volume to
      stromal volume changed in the favor of seminiferous tubule volume. It was
      observed that interstitial tissue became more regular and had a good organized
      structure with the progress of gestational age. In the third trimester, the lumen
      in the seminiferous tubules became more regular and clear and the interstitial
      tissue had a clear appearance.

PMID- 11245995
TI  - The role of blood transfusions and iron intake on retinopathy of prematurity.
AB  - BACKGROUND: The role of blood transfusions and iron intake in the pathogenesis or
      retinopathy of prematurity (ROP) is controversial. AIM: To evaluate the influence
      of packed red cell (PRC) transfusions and iron intake on ROP incidence. STUDY
      DESIGN: Prospective observational study. SUBJECTS: Forty-five preterm infants
      with birthweight <1250 g were studied. After ophthalmological study, they were
      divided into group A (n=24) that included newborns without ROP, and group B
      (n=21) that included newborns with ROP. RESULTS: Logistic regression analysis
      demonstrated that gestational age (OR 0.61; 95% C.I. 0.41-0.90), transfusion
      volume during the first week (OR 1.16; 95% C.I. 1.03-1.3) and during the first 2
      months of life (OR 2.93; 95% C.I. 1.52-5.62), and iron intake during the first
      week of life (OR 1.15; C.I. 1.01-1.32) and during the first 2 months of life (OR
      2.93; 95% C.I. 1.52-5.62) were associated with the development of ROP.
      CONCLUSION: Our study showed that gestational age, blood transfusion volume and
      iron load by transfusions are associated with the risk of occurrence of ROP in
      infants with a birthweight of less than 1250 g.

PMID- 11245997
TI  - The effect of shoulder-girdle loading by a school bag on lung volumes in Chinese
      primary school children.
AB  - BACKGROUND: Heavy loading of the spine may induce musculoskeletal problems in
      children. Local surveys reported frequent overloading of school bags carried by
      primary school children. The effect of an overweight school bag on the child's
      lung function has not been reported. AIMS: To investigate the effect of shoulder
      girdle loading on forced expiratory lung volumes in primary school children and
      to compare this effect with that of an assumed kyphotic posture. STUDY DESIGN AND
      SUBJECTS: Forty-three primary school children, mean age 9.6 years underwent
      spirometry lung-function measurements, while adopting the following five
      conditions in random order: free standing; kyphotic standing; standing wearing a
      backpack weighing 10%, 20% and 30% of their body weight. OUTCOMES MEASURES:
      Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC)
      and peak expiratory flow rate (PEF). RESULTS: There were no significant
      differences in FEV1 and FVC between free standing and the 10% body weight load.
      However, both FEV1 and FVC decreased significantly when the student adopted the
      kyphotic posture and when the load in the backpack was increased to 20% and 30%
      of body weight. CONCLUSIONS: This study demonstrates a restrictive effect on lung
      volumes when a school-bag load is heavier than 10% of a child's body weight. Our
      results also confirm the detrimental effect of a kyphotic posture on pulmonary
      mechanics and the necessity for health-care professionals to advocate proper
      postural advice to school children, teachers and parents.

PMID- 11245999
TI  - Molecules involved in the formation of synaptic connections in muscle and brain.
AB  - Synapses are highly specialized structures designed to guarantee precise and
      efficient communication between neurons and their target cells. Molecules of the
      extracellular matrix have an instructive role in the formation of the
      neuromuscular junction, the best-characterized synapse. In this review, the
      molecular mechanisms underlying these instructive signals will be discussed with
      particular emphasis on the receptors involved. Additionally, recent evidence for
      the involvement of specific adhesion complexes in the formation and modulation of
      synapses in the central nervous system will be reviewed. Synapses are specialized
      junctions between neurons and their target cells where information is transferred
      from the pre- to the postsynaptic cell. At most vertebrate synapses, this
      transfer is accomplished by the release of a specific neurotransmitter from the
      presynaptic nerve terminal. The release of neurotransmitter is initiated by the
      action potential and the subsequent influx of Ca(2+) into the presynaptic nerve
      terminal. This results in the rapid fusion of vesicles with the nerve membrane
      and the release of the neurotransmitter into the synaptic cleft. The
      neurotransmitter then diffuses across the cleft and binds to specific
      postsynaptic receptors, resulting in a change in the membrane potential of the
      postsynaptic cell. This can result in the generation of an action potential. The
      high precision of synaptic transmission requires that pre- and postsynaptic
      structures are both highly organized and in juxtaposition to each other. In
      addition, alterations in synaptic transmission are the basis of learning and
      memory and are likely to be accompanied by the remodeling of synaptic structures
      (Toni et al., 1999). Thus, the study of how synapses are formed during
      development is also of relevance for the understanding of the cellular and
      molecular processes involved in learning and memory. This review focuses on the
      molecular mechanisms involved in the formation and the function of synapses.

PMID- 11246000
TI  - The structure and function of tenascins in the nervous system.
AB  - The tenascins are a family of large extracellular matrix glycoproteins that
      comprise five known members. Three of these, tenascin-C (TN-C) tenascin-R (TN-R)
      and tenascin-Y (TN-Y) are expressed in specific patterns during nervous system
      development and are down-regulated after maturation. The expression of TN-C, the
      best studied member of the family, persists in restricted areas of the nervous
      system that exhibit neuronal plasticity and is reexpressed after lesion. Numerous
      studies in vitro suggest specific roles for tenascins in the nervous system
      involving precursor cell migration, axon growth and guidance. TN-C has been shown
      to occur in a large number of isoform variants generated by combinatorial
      variation of alternatively spliced fibronectin type III (FNIII) repeats. This
      finding indicates that TN-C might specify neural microenvironments, a hypothesis
      supported by recent analysis of TN-C knockout animals, which has begun to reveal
      subtle nervous system dysfunctions.

PMID- 11246001
TI  - Proteoglycans in the nervous system--the quest for functional roles in vivo.
AB  - Large numbers of different proteoglycans are expressed in tightly regulated
      spatio-temporal patterns by both the nerve cells (neurons) and the supporting
      glial cells of the nervous system. Several of these proteoglycans have been shown
      by studies in vitro to affect the migration of neural precursor cells, the
      elongation and pathfinding of neurites and the formation and stabilization of
      synapses. Such processes are important for the accurate wiring of the nervous
      system, and so it has been postulated that proteoglycans play an essential role
      during neural development. However, with few exceptions, the phenotypes of null
      mutations in mice and some human genetic diseases have provided little support
      for this view. Here we will review recent data from both in vitro and in vivo
      studies analyzing the function of proteoglycans in the nervous system in order to
      provide possible explanations for their apparent lack of function.

PMID- 11246002
TI  - In the mammalian eye type VI collagen tetramers form three morphologically
      different aggregates.
AB  - The organization of the aggregates occurring in the stroma: (1) of the murine and
      human cornea after incubation in an ATP acidic solution; (2) of surgically
      excised epiretinal membranes (ERM); and (3) of the trabecular meshwork of monkey
      eyes was investigated morphologically and immunocytochemically on thin section
      electron microscopy. Morphology. The aggregates in the cornea appeared as cross
      banded fibrils. The bands were uniformly electron dense (single banded form);
      they were separated from each other by interbands consisting of a bundle of
      filaments emerging in cross section as small areas of randomly assembled dot-like
      structures. In the ERM, most of the aggregates stood out as heteromorphic cross
      banded bodies showing dense bands with electron denser borders (double banded
      form) and interbands composed of longitudinally oriented, parallel sheets or
      laminae of amorphous material enclosing thin, similarly oriented filaments. These
      extended, thinner and double in number (since interlacing with similar components
      of the opposite sheet), into the pale central zone of the dense band. The
      aggregates of the trabecular meshwork were heteromorphic, had uniformly dense
      bands (single banded form as in the cornea), but their interbands displayed
      longitudinal sheets (as the ERM aggregates). Immunocytochemistry revealed type VI
      collagen in the three eye aggregates with gold particles preferentially localized
      at the interbands. The specificity of the antibodies used was tested by Western
      blot analysis of type VI collagen samples extracted from human placenta and on
      homogenates of human cornea. In conclusion, the results indicate that the
      tetramers of type VI collagen may aggregate differently into structures with
      distinct supramolecular arrangements. These are illustrated in schematic
      drawings.

PMID- 11246003
TI  - Differential expression of two exons of the alpha1(XI) collagen gene (Col11a1) in
      the mouse embryo.
AB  - The amino terminal domain of collagen XI has a unique structure, which is
      believed to participate in the regulation of matrix assembly. Interestingly,
      several distinct isoforms of the amino terminal domain of alpha1(XI) and
      alpha2(XI) collagen chains exist as a result of alternative splicing. Here we
      report the analysis of the alternative splicing pattern of the mouse alpha1(XI)
      collagen gene (Col11a1). Like other vertebrate species, the mutually exclusive
      expression of exons 6A and 6B of Col11a1 results in the inclusion in the alpha1
      chain of either an acidic peptide (pI 3.14) or a basic peptide (pI 11.66).
      Expression of these two exons was monitored in several tissues of the 16.5-day
      mouse embryo by in situ hybridization and immunohistochemistry, with exon
      specific cDNA probes and peptide-specific antibodies, respectively. The results
      documented that isoforms containing the exon 6B-encoded peptide accumulate
      predominantly in the vertebrae, skeletal muscles and intestinal epithelium. By
      contrast, exon 6A products were found to be most abundant in the smooth muscle
      cells of the intestine, aorta and lung. The results using in situ hybridization
      confirmed those using immunohistochemistry. Albeit correlative, the evidence
      suggests distinct contributions of the two peptides to the differential assembly
      of tissue-specific matrices.

PMID- 11246004
TI  - Identification of a novel heparin-binding site in the alternatively spliced IIICS
      region of fibronectin: roles of integrins and proteoglycans in cell adhesion to
      fibronectin splice variants.
AB  - The extracellular matrix molecule fibronectin (FN) is a glycoprotein whose major
      functional property is to support cell adhesion. FN contains at least two
      distinct cell-binding domains: the central cell-binding domain and the
      HepII/IIICS region. The HepII region comprises type III repeats 12-14 and
      contains proteoglycan-binding sites, while the alternatively spliced IIICS
      segment possesses the major alpha4beta1 integrin-binding sites. Both cell surface
      proteoglycans and integrins are important for mediating the adhesion of cells to
      this region of FN. By comparing heparin binding to different recombinant splice
      variants of the HepII/IIICS region, evidence was obtained for the existence of a
      novel heparin-binding site in the centre of the IIICS. Site-directed mutagenesis
      of basic amino acid sequences in this region reduced heparin binding to
      recombinant HepII/IIICS proteins and, in conjunction with mutations in the HepII
      region, caused a synergistic loss of activity. Using the H/120 variant of FN,
      which contains type III repeats 12-15 and the full-length IIICS region, and the
      H/95 variant of FN, which contains type III repeats 12-15 but lacks the high
      affinity integrin-binding LDV sequence, the relative roles played by cell-surface
      proteoglycans and integrins in mediating cell adhesion have been investigated.
      This was achieved by studying the effects of anti-integrin antibodies and
      exogenous heparin on A375 melanoma cell attachment to the wild-type and three
      different mutants of H/120 and H/95 in which the potential proteoglycan-binding
      sites were partially or completely removed. A375 cell adhesion to H/120 and its
      mutants was found to involve the co-operative action of both integrin and cell
      surface proteoglycan binding, although integrin made a dominant contribution.
      Anti-integrin antibodies and exogenous heparin were capable of inhibiting
      melanoma cell adhesion to H/95 and in this case adhesion was due primarily to
      cell-surface proteoglycan and not integrin binding.

PMID- 11246005
TI  - The archaeal homolog of the Imp4 protein, a eukaryotic U3 snoRNP component.
AB  - Homologs of the Imp4 protein, a component specific to the eukaryotic U3 snoRNP
      complex, have been found in all archaeal genomes. The archaeal and eukaryotic
      Imp4 proteins that are related to four other protein families, the Imp4-like, the
      SSF1 homologs and two sets of hypothetical proteins, are characterized by the
      Imp4 signature pattern. These findings, together with the presence of other
      snoRNPs homologs in Archaea, provide evidence for similar RNA processing and
      folding in Eukarya and Archaea.

PMID- 11246006
TI  - DDT -- a novel domain in different transcription and chromosome remodeling
      factors.
AB  - Homology-based sequence analyses have revealed the presence of a novel domain
      (DDT) in bromodomain PHD finger transcription factors (BPTFs), chromatin
      remodeling factors of the BAZ-family and other putative nuclear proteins. This
      domain is characterized by a number of conserved aromatic and charged residues
      and is predicted to consist of three alpha helices. Recent studies indicate a
      likely DNA-binding function for the DDT domain.

PMID- 11246007
TI  - The protease-associated domain: a homology domain associated with multiple
      classes of proteases.
AB  - The non-catalytic part of proteases frequently harbours domains responsible for
      regulation or targeting. Here, we describe a novel sequence motif conserved in
      proteins that belong to different protease superfamilies, the subtilases and Zn
      containing metalloproteases. The structure of the transferrin receptor, a
      catalytically inactive member of the latter family, suggests that the protease
      associated domain forms a lid structure that covers the active site. In addition
      to proteases, the domain is also found in two different families of plant
      vacuolar sorting receptors.

PMID- 11246012
TI  - Revised nomenclature for high mobility group (HMG) chromosomal proteins.

PMID- 11246020
TI  - Microsomal monooxygenase in apoptosis: another target for cytochrome c signaling?
AB  - The main function of eukaryotic microsomal monooxygenase (MMO) is thought to be
      the oxygenation of xenobiotics and hydrophobic endogenous substrates. However,
      there are important inconsistencies in the concept that the biological role of
      MMO is limited to the catalysis of these reactions. It is probable that MMO is
      also a regulated generator of reactive oxygen species (ROS) that is involved in
      both the initiation and execution of apoptosis. Additional support for this
      hypothesis came with the discovery of a role for cytochrome c (cyt c) in
      apoptotic signaling. This article introduces the theory that microsomal
      cytochrome b(5), which modulates the production of ROS in MMO, is among the
      principal interacting targets of cyt c. The role of this interaction in the
      initiation of apoptosis is discussed.

PMID- 11246021
TI  - Substrate assisted catalysis -- application to G proteins.
AB  - The idea that both the substrate and the enzyme contribute to catalysis
      (substrate assisted catalysis; SAC) is applicable to guanine nucleotide-binding
      proteins (G proteins). Naturally occurring SAC uses GTP as a general base in the
      GTPase reaction catalyzed by G proteins. Engineered SAC has identified a putative
      rate-limiting step for the GTPase reaction and shown that GTPase-deficient
      oncogenic Ras mutants are not irreversibly impaired. Thus, anti-cancer drugs
      could potentially be designed to restore the blocked GTPase reaction.

PMID- 11246022
TI  - HMG1 and 2, and related 'architectural' DNA-binding proteins.
AB  - The HMG-box proteins, one of the three classes of high mobility group (HMG)
      chromosomal proteins, bend DNA and bind preferentially to distorted DNA
      structures. The proteins appear to act primarily as architectural facilitators in
      the assembly of nucleoprotein complexes; for example, in effecting recombination
      and in the initiation of transcription. HMG-box proteins might be targeted to
      particular DNA sites in chromatin by either protein-protein interactions or
      recognition of specific DNA structures.

PMID- 11246023
TI  - The world according to PARP.
AB  - An immediate cellular response to DNA damage is the synthesis of poly(ADP-ribose)
      by the enzyme poly(ADP-ribose) polymerase (PARP). This nuclear enzyme and the
      unique post-translational modification it catalyzes have long been considered to
      function exclusively in cellular surveillance of genotoxic stress. The recent
      identification of multiple members of a PARP family might force a revision of
      this concept. The novel primary structures and subcellular localizations for some
      of these PARPs suggests new and unexpected roles for poly(ADP-ribosyl)ation in
      telomere replication and cellular transport.

PMID- 11246024
TI  - Metabolic modeling of microbial strains in silico.
AB  - The large volume of genome-scale data that is being produced and made available
      in databases on the World Wide Web is demanding the development of integrated
      mathematical models of cellular processes. The analysis of reconstructed
      metabolic networks as systems leads to the development of an in silico or
      computer representation of collections of cellular metabolic constituents, their
      interactions and their integrated function as a whole. The use of quantitative
      analysis methods to generate testable hypotheses and drive experimentation at a
      whole-genome level signals the advent of a systemic modeling approach to cellular
      and molecular biology.

PMID- 11246025
TI  - I kappa B-independent control of NF-kappa B activity by modulatory
      phosphorylations.
AB  - Activation of the transcription factor nuclear factor kappa B (NF-kappa B)
      requires its release from inhibitor of NF-kappa B (I kappa B) proteins in the
      cytoplasm. Much work has focussed on the identification of pathways regulating
      this cytosolic rate-limiting step of NF-kappa B activation. However, there is
      increasing evidence for another complex level of NF-kappa B activation, which
      involves modulatory phosphorylations of the DNA-binding subunits. These
      phosphorylations can control several functions of NF-kappa B, including DNA
      binding and transactivation properties, as well as interactions between the
      transcription factor and regulatory proteins. Although their overall impact on NF
      kappa B function has yet to be determined, modifications of this factor will very
      probably provide a mechanism to fine tune NF-kappa B function.

PMID- 11246026
TI  - Serine proteinase inhibitors from nematodes and the arms race between host and
      pathogen.
AB  - Serine proteinase inhibitors are encoded by a large gene family of long
      evolutionary standing. Recent discoveries of parasite proteins that inhibit human
      serine proteinases, together with the complete genomic sequence from
      Caenorhabditis elegans, have provided a set of new serine proteinase inhibitors
      from more primitive metazoan animals such as nematodes. The structural features
      (e.g. reactive centre residues), gene organization (including intron
      arrangements) and inhibitory function and targets (e.g. inflammatory and
      coagulation pathway proteinase) all contribute important new insights into
      proteinase inhibitor evolution. Some parasite products have evolved that block
      enzymes in the mammalian host, but the human host responds with a significant
      immune response to the parasite inhibitors. Thus, infection produces a finely
      balanced conflict between host and pathogen at the molecular level, and this
      might have accelerated the evolution of these proteins in parasitic species as
      well as their hosts.

PMID- 11246027
TI  - The Wiskott-Aldrich syndrome protein (WASP) family.

PMID- 11246028
TI  - Hantavirus.
AB  - Although hantaviruses have been known to exist for over 40 years, they were
      thought only to be the cause of hemorrhagic fever and renal syndrome (HFRS) in
      Europe and Asia. Rodents are the primary hosts of hantaviruses, and humans become
      infected mainly by inhalation of viral particles in the rodent excreta. The
      United States was thought to be spared from pathologic hantaviruses until the
      summer of 1993, when an outbreak of acute respiratory distress syndrome occurred
      in the Four Corners region of the United States, which includes Colorado, New
      Mexico, Arizona, and Utah. Through serological studies, the etiologic agent of
      this respiratory disease was found to be a heretofore-unknown hantavirus that was
      named the Sin Nombre virus. The resulting condition was renamed Hantavirus
      Pulmonary Syndrome (HPS). HPS begins as a febrile prodrome and quickly progresses
      to a life-threatening cardiorespiratory failure. A laboratory triad of
      thrombocytopenia, leucocytosis with bandemia, and immunoblasts is specific to
      HPS, and enzyme-linked immunosorbent assay remains the gold standard for
      diagnosis of hantaviruses. The management of both HFRS and HPS is mainly
      supportive, although ribavirin has been shown to be useful for HFRS. Eliminating
      exposure to rodents remains the key to prevention of hantavirus infection.

PMID- 11246030
TI  - Amebiasis.
AB  - Human amebiasis is caused by the protozoan parasite Entamoeba histolytica.
      Invasion of the colonic mucosa by the trophozoite form of this parasite generally
      results in the clinical syndrome of amebic dysentery, although there is a wide
      range of clinical presentations. Some patients will progress to disseminated
      disease, with resulting amebic liver abscesses. Although it is estimated that 10%
      of the world's population is infected with E. histolytica, only 1% of these
      patients will manifest disease. The diagnosis is usually made by microscopically
      identifying the microorganism in a stool specimen. The antibiotic of choice for
      treatment of amebiasis is metronidazole, 750 mg, three times daily for 10 days.

PMID- 11246029
TI  - The protease inhibitors.
AB  - With the advent of newer antiretroviral agents for the treatment of patients with
      human immunodeficiency virus (HIV) infection and acquired immune deficiency
      syndrome (AIDS), health care providers are faced with many options to optimize
      their patients' therapy. Currently, there are three groups of drugs available for
      the treatment of patients with HIV infection: nucleoside reverse transcriptase
      inhibitors (also known as nucleoside analogues), nonnucleoside reverse
      transcriptase inhibitors, and protease inhibitors (PIs). The preferred initial
      treatment regimen now consists of two nucleoside analogues and a PI. Protease
      inhibitors cause profound and sustained suppression of viral replication,
      increase time to first AIDS-defining illness, and reduce mortality. Each of the
      available PIs have distinct pharmacokinetic and metabolic properties that result
      in different dosing regimens and potential for interactions with food and other
      drugs. Patients with HIV infection typically receive several drugs; therefore,
      convenience of administration, optimal side-effect profile, and cost of the
      agents must also be considered along with the potential for drug interactions.A
      growing proportion of HIV patients worldwide are women. HIV-infected pregnant
      women should be offered antiretroviral prophylaxis to prevent perinatal HIV
      transmission as well as to optimize their own health. Zidovudine (ZDV) treatment
      has been the standard antiretroviral treatment during pregnancy; however, recent
      data has shown that combination regimens produce a more pronounced antiviral
      effect and may be more effective than ZDV monotherapy in preventing perinatal HIV
      transmission.

PMID- 11246031
TI  - A survey on the management of nausea and vomiting in pregnancy by
      obstetrician/gynecologists.
AB  - Our objective was to survey obstetrician/gynecologists concerning their
      management of nausea and vomiting in pregnancy. We mailed a survey on nutrition
      during pregnancy to the 230 ACOG Fellows who are members of the Collaborative
      Ambulatory Research Network and to a control sample of 800 non-Network Fellows.
      Results presented here are for the questions concerning prevalence and management
      of pregnancy-induced nausea. A total of 488 surveys (47.4% response rate) were
      analyzed. Respondents reported that on average, 51.4% of patients complain of
      nausea during pregnancy, and 9.2% complain of severe or prolonged nausea with
      vomiting. Respondents reported that on average, 2.4% of patients require
      hospitalization because of hyperemesis gravidarum. Treatments recommended by a
      majority of respondents for moderate nausea were eating frequent small meals
      (95.5%), snacking on soda crackers (88.5%), avoiding strong odors (75.6%), taking
      a prescribed antiemetic (71.3%), taking ginger (51.8%), and eliminating iron
      supplements (50%). Women physicians were more likely to recommend ginger and less
      likely to prescribe an antiemetic. For severe and sustained nausea with vomiting,
      with additional symptoms such as dehydration or weight loss, intravenous
      hydration (88.7%) and antiemetics (74.0%) were the most common treatment options.
      Almost half (48.8%) of respondents would hospitalize such patients. We conclude
      that obstetrician/gynecologists appear to be knowledgeable concerning current
      opinion on managing nausea and vomiting of pregnancy. Improvements in the
      management of nausea during pregnancy are more likely to come from further
      research, not education of physicians.

PMID- 11246032
TI  - Infectious mononucleosis.
AB  - Infectious mononucleosis in its classical presentation consists of the clinical
      triad of fever, pharyngitis, and cervical lymphadenopathy. The majority of cases
      are caused by primary infection with the Epstein-Barr virus (EBV). There is,
      however, a wide clinical spectrum of disease manifestations, including pulmonary,
      hematologic, and neurologic findings and a series of associated laboratory
      abnormalities, such as lymphocytosis, heterophile antibodies, and anti-EBV
      antibodies. The disease is typically self-limited and treated with supportive
      therapy only. Rarely, serious complications such as airway obstruction, severe
      thrombocytopenia, or severe hemolytic anemia can occur. Infectious mononucleosis
      does not cause congenital anomalies, and pregnant women are not at increased risk
      of serious complications resulting from the disorder.

PMID- 11246033
TI  - Folic acid and preconceptional care.
AB  - If all women capable of becoming pregnant consumed 400 ug (0.4 mg) of the B
      vitamin folic acid daily before conception and during the first trimester, the
      annual number of neural-tube birth defect (NTD)-affected pregnancies in this
      country could be reduced by 50% to 70%. Despite this important relationship, most
      women are not aware that folic acid prevents NTDs, and folic acid supplementation
      rates remain low. If folic acid consumption is to succeed as a public health
      intervention on a societal scale, physicians who care for reproductive-age women
      must become informed about the folic acid-NTD prevention linkage. Next, they must
      be encouraged to counsel patients about the need to consume sufficient folic acid
      before conception. Studies reveal that few physicians have adequate knowledge of
      the appropriate timing and dosage of folic acid supplementation. Studies also
      show that women are more likely to get important folic acid information not from
      their physicians but from other sources. This article provides information about
      ways in which physicians can improve their folic acid knowledge and education
      practices.

PMID- 11246034
TI  - Clinical management of insomnia: pharmacological and psychological strategies.
AB  - Each year, insomnia affects more than 60 million adults in the United States-a
      startling 30% to 50% of the general population. It is one of the most common
      presenting complaints in primary care and, like so many mental health problems,
      disproportionally affects women. Sleep research demonstrates that women need as
      much as an hour and a half more sleep than men-a (suggested) total of 8-9 hours
      of sleep per day. For both men and women, a good night's sleep is essential to
      overall physical and mental health. Sleep needs among individuals vary a great
      deal, but a basic step that anyone can take to feel healthy, increase energy, and
      even fight physical disease is to get as much sleep as needed.1

PMID- 11246035
TI  - Physiological consequences of feeding in animals. Symposium proceedings. Exeter,
      United Kingdom, 27-31 March 2000.

PMID- 11246036
TI  - Prey processing in amniotes: biomechanical and behavioral patterns of food
      reduction.
AB  - In this paper we examine the biomechanics of prey processing behavior in the
      amniotes. Whether amniotes swallow prey items whole or swallow highly processed
      slurries or boluses of food, they share a common biomechanical system where hard
      surfaces (teeth or beaks) are brought together on articulated jaws by the actions
      of adductor muscles to grasp and process food. How have amniotes modified this
      basic system to increase the chewing efficiency of the system? To address this
      question we first examine the primitive condition for prey processing
      representative of many of the past and present predatory amniotes. Because
      herbivory is expected to be related to improved prey processing in the jaws we
      review patterns of food processing mechanics in past and present herbivores.
      Herbivory has appeared numerous times in amniotes and several solutions to the
      task of chewing plant matter have appeared. Birds have abandoned jaw chewing in
      favor of a new way to chew--with the gut--so we will detour from the jaws to
      examine the appearance of gut chewing in the archosaurs. We will then fill in the
      gaps among amniote taxa with a look at some new data on patterns of prey
      processing behavior and jaw mechanics in lizards. Finally, we examine
      evolutionary patterns of amniote feeding mechanism and how correlates of chewing
      relate to the need to increase the efficiency of prey processing in order to
      facilitate increased metabolic rate and activity.

PMID- 11246037
TI  - Neural modulation of visuomotor functions underlying prey-catching behaviour in
      anurans: perception, attention, motor performance, learning.
AB  - The present review points out that visuomotor functions in anurans are modifiable
      and provides neurophysiological data which suggest modulatory forebrain
      functions. The retino-tecto/tegmento-bulbar/spinal serial processing streams are
      sufficient for stimulus-response mediation in prey-catching behaviour. Without
      its modulatory connections to forebrain structures, however, these processing
      streams cannot manage perceptual tasks, directed attention, learning
      performances, and motor skills. (1) Visual prey/non-prey discrimination is based
      on the interaction of this processing stream with the pretectal thalamus
      involving the neurotransmitter neuropeptide-Y. (2) Experiments applying the
      dopamine agonist apomorphine in combination with 2DG mapping and single neurone
      recording suggest that prey-catching strategies in terms of hunting prey and
      waiting for prey depend on dose dependent dopaminergic adjustments in the neural
      macronetwork in which retinal, pretecto-tectal, basal ganglionic, limbic, and
      mesolimbic structures participate. (3) Visual response properties of striatal
      efferent neurones support the concept that ventral striatum is involved in
      directed attention. (4) Various modulatory loops involving the ventral medial
      pallium modify prey-recognition in the course of visual or visual-olfactory
      learning (associative learning) or are responsible for stimulus-specific
      habituation (non-associative learning). (5) The circuits suggested to underlie
      modulatory forebrain functions are accentuated in standard schemes of the neural
      macronetwork. These provide concepts suitable for future decisive experiments.

PMID- 11246038
TI  - Consequences of feeding for future feeding.
AB  - The intake of food has physiological consequences via physical (e.g. distension)
      and chemical (e.g. glucose) stimulation of receptors in the viscera and, in the
      longer term, by changes in signals from adipose tissue (e.g. leptin), integrated
      by the CNS. These consequences are associated with the sensory properties of the
      food such that repeated exposure to a food generates a conditioned acceptance or
      rejection reflex with the physiological consequences of eating as the
      unconditioned stimulus (US) and the sensory characteristics of the food as the
      conditioned stimulus (CS). Such learnt preferences and aversions occur throughout
      the animal kingdom, from nematodes to human beings, with much of the research
      being carried out with insects, laboratory animals and farm animals. Preferences
      for and aversions to particular foods are manifested in non-random choices
      between two or more foods on offer but also influence the quantity eaten when
      only one food is available. These considerations have been developed into a
      theory of Minimal Total Discomfort which proposes that an animal experiments with
      the amount eaten per day, and its selection between different foods, until the
      total of the signals generated from excesses or deficiencies of food components
      is minimised. Changes in food composition and/or nutrient requirements can
      therefore be matched by appropriate changes in intake and selection.

PMID- 11246039
TI  - Regulatory peptides and control of food intake in non-mammalian vertebrates.
AB  - The current view of the control of food intake involves a central feeding system
      in the hypothalamus receiving input from peripheral systems. The presence of food
      in the gut stimulates the release of several regulatory peptides that control gut
      motility and secretion. Some of these peptides also act as feedback satiety
      signals, responsible for termination of a meal. Among the regulatory peptides
      suggested as peripheral satiety signals are cholecystokinin and gastrin releasing
      peptide. A more long-term peripheral regulation of food intake has also been
      postulated and leptin has been suggested as a regulator of food intake. Several
      regulatory peptides mediate orexigenic or anorexigenic effects in the central
      feeding system. Neuropeptide Y and galanin both act centrally and stimulate the
      intake of food, while corticotropin releasing factor reduces food intake. At
      present, most information about the regulation of food intake is gained from
      mammalian studies and these findings are used as a base for a discussion on the
      current knowledge of how regulatory peptides control appetite in non-mammalian
      vertebrates.

PMID- 11246040
TI  - The control of gut motility.
AB  - Gut motility in non-mammalian vertebrates as in mammals is controlled by the
      presence of food, by autonomic nerves and by hormones. Feeding and the presence
      of food initiates contractions of the stomach wall and subsequently gastric
      emptying, peristalsis, migrating motor complexes and other patterns of motility
      follow. This overview will give examples of similarities and differences in
      control systems between species. Gastric receptive relaxation occurs in fish and
      is an enteric reflex. Cholecystokinin reduces the rate of gastric emptying in
      fish as in mammals. Inhibitory control of peristalsis is exerted, e.g. by VIP,
      PACAP, NO in fish and amphibians, while excitatory stimuli arise from nerves
      releasing tachykinins, acetylcholine or serotonin (5-HT). In crocodiles, we have
      found the presence of the same nerve types, although the effects on peristalsis
      have not been studied. Recent studies on signal transduction in the gut smooth
      muscle of fish and amphibians suggest that external Ca2+ is of great importance,
      but not the only source of Ca2+ recruitment in tachykinin-, acetylcholine- or
      serotonin-induced contractions of rainbow trout and Xenopus gastrointestinal
      smooth muscle. The effect of acetylcholine involves reduction of cAMP-levels in
      the smooth muscle cells. It is concluded that, in general, the control systems in
      non-mammalian vertebrates are amazingly similar between species and animal groups
      and in comparison with mammals.

PMID- 11246041
TI  - Control of gastric acid secretion:the gastrin-ECL cell-parietal cell axis.
AB  - Gastric acid secretion is under nervous and hormonal control. Gastrin, the major
      circulating stimulus of acid secretion, probably does not stimulate the parietal
      cells directly but acts to mobilize histamine from the ECL cells in the oxyntic
      mucosa. Histamine stimulates the parietal cells to secrete HCl. The gastrin-ECL
      cell pathway has been investigated extensively in situ (gastric submucosal
      microdialysis), in vitro (isolated ECL cells) and in vivo (intact animals).
      Gastrin acts on CCK2 receptors to control the synthesis of ECL-cell histamine,
      accelerating the expression of the histamine-forming enzyme histidine
      decarboxylase (HDC) at both the transcription and the translation/posttranslation
      levels. Depletion of histamine by alpha-fluoromethylhistidine (an irreversible
      inhibitor of HDC) prevents gastrin-induced but not histamine-induced gastric acid
      secretion. Acute CCK2 receptor blockade inhibits gastrin-evoked but not histamine
      induced acid secretion. Studies both in vivo/in situ and in vitro have suggested
      that while acetylcholine seems capable of activating parietal cells, it does not
      affect histamine secretion from ECL cells. Unlike acetylcholine, the
      neuropeptides pituitary adenylate cyclase-activating peptide and vasoactive
      intestinal peptide mobilize ECL-cell histamine. Whether vagally stimulated acid
      secretion reflects an effect of the enteric nervous system on the ECL cells
      (neuropeptides) and/or a direct one on the parietal cells needs to be further
      investigated.

PMID- 11246042
TI  - Energetic and physiological correlates of prey handling and ingestion in lizards
      and snakes.
AB  - In this review, we summarize the energetic and physiological correlates of prey
      handling and ingestion in lizards and snakes. There were marked differences in
      the magnitude of aerobic metabolism during prey handling and ingestion between
      these two groups, although they show a similar pattern of variation as a function
      of relative prey mass. For lizards, the magnitude of aerobic metabolism during
      prey handling and ingestion also varied as a function of morphological
      specializations for a particular habitat, prey type, and behavior. For snakes,
      interspecific differences in aerobic metabolism during prey handling seem to be
      correlated with adaptations for prey capture (venom injection vs. constriction).
      During ingestion by snakes, differences in aerobic metabolism might be due to
      differences in cranial morphology, although allometric effects might be a
      potentially confounded effect. Anaerobic metabolism is used for prey handling and
      ingestion, but its relative contribution to total ATP production seems to be more
      pronounced in snakes than in lizards. The energetic costs of prey handling and
      ingestion are trivial for both groups and cannot be used to predict patterns of
      prey-size selection. For lizards, it seems that morphological and ecological
      factors set the constraints on prey handling and ingestion. For snakes, besides
      these two factors, the capacity of the cardio-respiratory system may also be an
      important factor constraining the capacity for prey handling and ingestion.

PMID- 11246044
TI  - Gut blood flow in fish during exercise and severe hypercapnia.
AB  - This paper reviews the effects of exercise and hypercapnia on blood flow to the
      splanchnic circulation. Brief struggling behaviours are known to decrease blood
      flow to the gut (GBF). Likewise, prolonged swimming in unfed fish has been shown
      to reduce GBF in proportion to the increased oxygen uptake. Therefore, the normal
      postprandial increase in GBF theoretically should be impaired whenever fish are
      active. However, indirect evidence suggests that GBF is spared to some degree
      when fed fish swim continuously but at a cost (10-15%) to their critical swimming
      speed. Severe respiratory acidosis can be created by the new intensive
      aquaculture settings that use oxygen injection into re-circulated water. The only
      study so far to examine the effects of severe hypercapnia on GBF and its
      regulation showed that routine GBF and alpha-adrenergic control of GBF remained
      normal in unfed white sturgeon (Acipenser transmontanus). However, severe
      hypercapnia produced a hyperactive state and increased sensitivity of GBF to
      struggling. As a result, routine GBF was maintained for a short period of time.
      Thus, environmental changes such as severe hypercapnia can indirectly impact GBF
      through altered struggling behaviour, but the implications of the overall
      reduction in GBF to food assimilation have yet to be established.

PMID- 11246043
TI  - The respiratory consequences of feeding in amphibians and reptiles.
AB  - Many ectothermic vertebrates ingest very large meals at infrequent intervals. The
      digestive processes associated with these meals, often coupled with an extensive
      hypertrophy of the gastrointestinal organs, are energetically expensive and
      metabolic rate, therefore, increases substantially after feeding (specific
      dynamic action, SDA). Here, we review the cardio-respiratory consequences of SDA
      in amphibians and reptiles. For some snakes, the increased oxygen uptake during
      SDA is of similar magnitude to that of muscular exercise, and the two
      physiological states, therefore, exert similar and profound demands on oxygen
      transport by the cardiorespiratory systems. In several species, SDA is attended
      by increases in heart rate and overall systemic blood flows, but changes in blood
      flow distribution remain to be investigated. In snakes, the regulation of heart
      rate appears to involve a non-adrenergic-non-cholinergic mechanism, which may be
      a regulatory peptide released from the gastrointestinal system during digestion.
      Digestion is also associated with a net acid secretion to the stomach that causes
      an increase in plasma HCO3- concentration (the 'alkaline tide'). Experiments on
      chronically cannulated amphibians and reptiles, show that this metabolic
      alkalosis is countered by an increased P(CO2), so that the change in arterial pH
      is reduced. This respiratory compensation of arterial pH is accomplished through
      a reduction in ventilation relative to metabolism, but the estimated reductions
      in lung P(O2) are relatively small. The SDA response is also associated with
      haematological changes, but large interspecific differences exist. The studies on
      cardiorespiratory responses to digestion may allow for a further understanding of
      the physiological and structural constraints that limits the ability of reptiles
      and amphibians to sustain high metabolic rates.

PMID- 11246045
TI  - Regulation of digestive performance: a proposed adaptive response.
AB  - Among snakes a correlation exists between feeding habits (frequent or infrequent)
      and the magnitude by which digestive performance is regulated (modest or large).
      This paper investigates whether the observed regulation of digestive performance
      is an adaptation to feeding habits and therefore, a product of natural selection.
      Using data on metabolic and intestinal responses to feeding for amphibians and
      reptiles, it is attempted to show the selective advantage and independent origin
      of either modestly or widely regulating gut performance. In an energetic model,
      snakes that naturally feed frequently on small meals benefit (from lower energy
      output) from modestly regulating gut performance as opposed to widely regulating
      gut performance. Likewise, the model suggests an energetic benefit for
      infrequently-feeding snakes secondary to the wide regulation of gut performance.
      This benefit is a function of long spans of fasting with a down-regulated gut
      (thereby incurring a lower standard metabolic rate) and the occasionally
      incursion of a costly up-regulation of the gut. In a comparison across several
      distantly-related lineages of amphibians and reptiles, frequently-feeding species
      all exhibit small postprandial responses in metabolism and intestinal nutrient
      transport capacities. In contrast, frogs and snakes that routinely fast for long
      periods independently experience five- to 30-fold increases in metabolism and
      intestinal performance with feeding. Among amphibians and reptiles the evidence
      presented supports the hypothesis that the extent by which the gut is regulated
      is an adaptive trait that evolved with divergence in feeding habits and energy
      budgets. In finishing, the foundations, caveats, and suggested future tests of
      this adaptive hypothesis are presented.

PMID- 11246046
TI  - Phenotypic flexibility in digestive system structure and function in migratory
      birds and its ecological significance.
AB  - Birds during migration must satisfy the high energy and nutrient demands
      associated with repeated, intensive flight while often experiencing unpredictable
      variation in food supply and food quality. Solutions to such different challenges
      may often be physiologically incompatible. For example, increased food intake and
      gut size are primarily responsible for satisfying the high energy and nutrient
      demands associated with migration in birds. However, short-term fasting or food
      restriction during flight may cause partial atrophy of the gut that may limit
      utilization of ingested food energy and nutrients. We review the evidence
      available on the effects of long- and short-term changes in food quality and
      quantity on digestive performance in migratory birds, and the importance of
      digestive constraints in limiting the tempo of migration in birds. Another
      important physiological consequence of feeding in birds is the effect of diet on
      body composition dynamics during migration. Recent evidence suggests that birds
      utilize and replenish both protein and fat reserves during migration, and diet
      quality influences the rate of replenishment of both these reserves. We conclude
      that diet and phenotypic flexibility in both body composition and the digestive
      system of migratory birds are important in allowing birds to successfully
      overcome the often-conflicting physiological challenges of migration.

PMID- 11246047
TI  - Protein synthesis and specific dynamic action in crustaceans: effects of
      temperature.
AB  - Temperature influences the specific dynamic action (SDA), or rise in oxygen
      uptake rate after feeding, in eurythermal and stenothermal crustaceans by
      changing the timing and the magnitude of the response. Intra-specific studies on
      the eurythermal crab, Carcinus maenas, show that a reduction in acclimation
      temperature is associated with a decrease in SDA magnitude, resulting from an
      increase in SDA duration but a decrease in peak factorial scope (the factorial
      rise in peak SDA over prefeeding values). Inter-specific feeding studies on
      stenothermal polar isopods revealed marked differences in SDA response between
      the Antarctic species, Glyptonotus antarcticus and the Arctic species, Saduria
      entomon. Compared to S. entomon held at 4 and 13 degrees C, the SDA response in
      G. antarcticus held at 1 degrees C was characterised by a lower absolute oxygen
      uptake rate at peak SDA and an extended SDA duration. At peak SDA, whole animal
      rates of protein synthesis increased in proportion to the postprandial increase
      in oxygen uptake rate in the Antarctic and the Arctic species. Rates of oxygen
      uptake plotted against whole animal rates of protein synthesis gave similar
      relationships in both isopod species, indicating similar costs of protein
      synthesis after a meal, despite their differences in SDA response and thermal
      habitat.

PMID- 11246048
TI  - Effects of dietary fatty acids on the respiratory and cardiovascular physiology
      of fish.
AB  - In animals, the composition of fatty acids (FAs) in body pools reflects dietary
      intake. This paper reviews evidence that the manipulation of tissue lipids of
      farmed fish, by feeding them different natural oils, can have significant effects
      on their respiratory and cardiovascular physiology. Sturgeon and eels with tissue
      lipids rich in highly unsaturated FAs of the n-3 series (n-3HUFAs, accumulated
      from dietary menhaden oil) had significantly lower metabolic rates than fish with
      tissues rich in saturated FAs (SFAs, from coconut oil), although they grew
      equally well. In sturgeon, the difference in metabolism influenced tolerance of
      hypoxia. Degrees of hypoxia that depressed oxygen uptake and spontaneous activity
      in fish rich in SFAs had no such effects on fish rich in n-3HUFAs. In the
      isolated sturgeon heart working in vitro, reduced oxygen supply depressed the
      performance of hearts with lipids rich in SFAs but not that of hearts rich in n
      3HUFAs. In salmon fed diets with graded mixtures of menhaden and canola oils,
      there was no relationship between tissue n-3HUFA content (from menhaden oil) and
      any measured aspect of swimming performance, but a linear relationship between
      maximum sustainable swimming speed and muscle oleic acid levels (from canola
      oil). Such exploratory studies indicate that an animal's responses to its
      environment may be profoundly affected by the oils and FAs it consumes in its
      diet.

PMID- 11246049
TI  - Digestion in relation to feeding strategies exhibited by crustacean larvae.
AB  - Decapod crustaceans have adopted a full range of reproductive strategies from the
      release of large numbers of small eggs (Penaeoidea) to the release of relatively
      low numbers of large advanced larvae (Nephropidae). As larval size determines
      trophic position in planktonic food webs, all food sources from phyto- to
      zooplankton are exploited, with many species changing trophic level during
      ontogenetic development. Comparative studies on digestive enzymes, levels of
      activity and changes during ontogeny, together with measurements of
      gastroevacuation rates and food energy values appear to reveal a general pattern.
      While herbivorous decapod larvae adapt to low food energy values with high enzyme
      activity levels, rapid food turnover and low assimilation efficiency, carnivorous
      larvae exhibit low levels of enzyme activity but compensate by extending
      retention time of high-energy food to maximise assimilation efficiency. New
      studies on digestive enzyme levels during development in the penaeid Litopenaeus
      vannamei, the caridean Lysmata debelius and the cirriped Elminius modestus,
      appear to agree with previous observations.

PMID- 11246050
TI  - Meeting energy budgets by modulation of behaviour and physiology in the eel
      (Anguilla anguilla L.).
AB  - Availability of energy for feeding, and the scope to accommodate the associated
      increase in oxygen demand (SDA: specific dynamic action) can, to a large degree,
      regulate the future feeding and energy availability of an animal. There is a
      fundamental conflict between locomotion and SDA within the physiological capacity
      of a mobile organism to respire sufficiently in order to simultaneously meet both
      requirements. This paper is a first attempt to integrate the costs of behaviour
      and physiology and produce a testable model of energy allocation in the eel.
      Total oxygen consumption (metabolic rate MO2) of the eel (Anguilla anguilla L.)
      was 109 micromol O2 x g(-1) x day(-1) with a cost of measured protein synthesis
      representing 49% of this value, and measured routine swimming (locomotor)
      activity representing approximately 34%. By allocating periods of reduced
      activity, the eel is able to develop a strategy to prudently meet the costs of
      feeding and temporally balance energy budgets (in terms of oxygen) by modulation
      of the behaviour and demands of physiology.

PMID- 11246051
TI  - Long-term fasting and re-feeding in penguins.
AB  - Spontaneous fasting during reproduction (sometimes with a full stomach) and moult
      is a major characteristic of the annual cycle of penguins. Long-term fasting (up
      to four months in male emperor penguins) is anticipated by the accumulation of
      fat (incubation fast) and of fat and protein (moult fast). During most of the
      incubation fast, birds rely almost entirely on lipids as an energy source, body
      proteins being spared. However, below a critical (but non-total) fat store
      depletion, marked behavioural, metabolic, and endocrine changes occur.
      Spontaneous locomotor activity increases and the egg is transitorily left
      unincubated for increasingly long periods, until its definitive abandon and the
      bird departs to re-feed at sea. These changes are thought to be activated by an
      endogenous re-feeding signal triggered before lethal energy depletion. An
      increase in body protein catabolism in the face of a reduction in lipid
      availability and utilisation, and an increase in circulating corticosterone vs. a
      decrease in plasma prolactin, are likely to be major metabolic and hormonal
      components of this signal. The survival and rapid restoration of energy stores in
      birds having departed to re-feed at a stage of near total lipid depletion
      demonstrates the effectiveness of the re-feeding signal. Penguins, and possibly
      other seabirds, are therefore appropriate animal models for understanding the
      long-term interactions between body energy reserves and fasting, breeding and
      feeding physiology and behaviour.

PMID- 11246052
TI  - Elevated serum levels of soluble interleukin-2 receptor, neopterin and beta-2
      microglobulin in idiopathic dilated cardiomyopathy: relation to disease severity
      and autoimmune pathogenesis.
AB  - BACKGROUND: It has not been assessed whether high levels of soluble interleukin 2
      receptor (sIL-2R), neopterin and beta-2 microglobulin in idiopathic dilated
      cardiomyopathy reflect heart failure severity and/or an active autoimmune
      process. The aim of this study was to relate serum levels of these markers to
      clinical and autoimmune features. METHODS: We studied 60 patients with idiopathic
      dilated cardiomyopathy, 67 controls with ischemic heart failure and 34 normals.
      RESULTS: Abnormal levels of sIL-2R, but not of neopterin and beta-2
      microglobulin, were more frequent in idiopathic dilated cardiomyopathy than in
      ischemic patients (35% vs. 16%; P=0.02) or in normals (35% vs. 12%, P=0.01); mean
      sIL-2R levels were, however, similar in idiopathic dilated cardiomyopathy and
      ischemic heart failure (842+/-75 vs. 762+/-93 U/ml, P=NS). In idiopathic dilated
      cardiomyopathy abnormal levels of sIL-2R were associated with lower peak oxygen
      consumption (P=0.008), higher neopterin and HLA class II expression in the
      myocardium (P=0.02), but were unrelated to cardiac autoantibody status or titer.
      In addition, abnormal levels of neopterin were associated with adverse prognosis
      and higher beta-2 microglobulin; abnormal levels of beta-2 microglobulin with
      lower echocardiographic percent fractional shortening, higher sIL-2R and higher
      neopterin. CONCLUSIONS: There is no convincing evidence that abnormal sIL-2R,
      neopterin and/or beta-2 microglobulin are disease-specific markers of idiopathic
      dilated cardiomyopathy. The lack of association with cardiac autoantibodies
      suggests that these abnormalities are mainly related to heart failure severity
      rather than autoimmune pathogenesis. In keeping with this view, high levels of
      sIL-2R, neopterin and/or beta-2 microglobulin identified a subset of idiopathic
      dilated cardiomyopathy patients with advanced disease and poor prognosis.

PMID- 11246054
TI  - Doppler echocardiography reliably predicts pulmonary artery wedge pressure in
      patients with chronic heart failure even when atrial fibrillation is present.
AB  - BACKGROUND AND AIMS: In patients with chronic congestive heart failure a high
      pulmonary artery wedge pressure (PAWP) is associated with poor prognosis, severe
      symptoms and low exercise tolerance. When atrial fibrillation is present the non
      invasive prediction of PAWP by Doppler echocardiography is generally considered
      to be not reliable. METHODS: In 51 consecutive patients with chronic heart
      failure, due to either ischemic and non-ischemic dilated cardiomyopathy, and
      atrial fibrillation simultaneous Doppler echocardiographic and hemodynamic
      studies were used to estimate PAWP. The power of the obtained multivariate
      equation was compared with that of previously developed equations and was then
      prospectively tested in a group of 15 patients. RESULTS: The deceleration rate
      (DR) of early diastolic mitral flow, the left ventricular iso-volumic relaxation
      time (IVRT) and the systolic fraction of pulmonary venous flow (SF) were
      independent predictors of PAWP and the following multivariable equation was
      derived: PAWP=24.04 + 1.23 x DR- 0.089 x IVRT - 0.175 x SF. The correlation
      between invasive PAWP and the PAWP non-invasively estimated by this equation in
      the testing group was 0.91 (standard error of estimate=3.2 mmHg). The mean
      difference was 0.93 and the standard error of differences was 2.7 mmHg.
      CONCLUSION: In patients with chronic heart failure due to dilated cardiomyopathy
      who are in atrial fibrillation a relatively accurate estimation of PAWP can be
      obtained by Doppler echocardiography of mitral and pulmonary venous flow.

PMID- 11246053
TI  - Increased circulating levels of ouabain-like factor in patients with asymptomatic
      left ventricular dysfunction.
AB  - BACKGROUND: Much evidence has been accumulated that human plasma contains
      digitalis-like factor(s) with Na/K ATPase inhibitor properties. Increased
      concentrations of ouabain-like factor (OLF) have been reported in patients with
      moderate to severe hypertension and in patients with overt congestive heart
      failure due to dilated cardiomyopathy. AIM: The presence of circulating OLF has
      not been investigated in borderline to mild hypertension or in the early stage of
      dilated cardiomyopathy. METHODS AND RESULTS: The study population consisted of 18
      normal volunteers, 24 patients with borderline to mild hypertension, 47 patients
      with asymptomatic left ventricular dysfunction (ALVD) due to dilated
      cardiomyopathy and 26 patients with cardiac arrhythmias but normal left
      ventricular function. OLF values (pM ouabain equivalent) were assayed in
      extracted plasma, using a radioimmunoassay for ouabain. OLF was, respectively,
      29.4+/-20.6 pM in normal controls, 39.1+/-23.8 pM in hypertensives, 35+/-18 pM in
      patients with cardiac arrhythmias, 52.3+/-25.8 pM in ALVD patients not treated
      with digoxin and 64.6+/-29.6 pM in ALVD patients treated with digoxin. Patients
      with ALVD, both treated and not treated with digoxin, had OLF significantly
      higher (P<0.05) than all the other groups. In patients with ALVD no correlation
      between OLF and left ventricular ejection fraction was observed. In the
      hypertensive group no correlation between OLF and both diastolic and systolic
      pressure was found. CONCLUSION: Increased concentrations of OLF were observed in
      patients with left ventricular dysfunction due to dilated cardiomyopathy, before
      the occurrence of overt heart failure, suggesting that OLF may be an early marker
      of the disease.

PMID- 11246055
TI  - Altered diaphragm position and function in patients with chronic heart failure.
AB  - BACKGROUND: Breathlessness is a common symptom experienced by patients with
      chronic heart failure (CHF) but its etiology remains controversial. Various
      molecular and histological adaptations have been reported for the diaphragm in
      CHF but their functional consequences are poorly described. AIMS: This study aims
      to determine the position and function of the diaphragm in CHF patients. METHODS:
      The diaphragm position was measured, relative to the renal pelvis, by ultrasound
      in 20 CHF patients and ninety controls matched for age and body mass. The extent
      and velocity of diaphragm movement was also measured during quiet breathing and
      sniffing. RESULTS: At the end of expiration, the diaphragm was significantly
      nearer to the renal pelvis in CHF patients (89.3+/-16.8 vs. 96.3+/-19.2 mm,
      P<0.05) and also moved further during quiet breathing (18.2+/-4.4 vs. 12.7+/-4.6
      mm, P<0.001) and sniffing (23.9+/-7.4 vs. 18.2+/-5.7 mm, P<0.005). Velocity of
      diaphragm movement was also increased in CHF patients during quiet breathing
      (26.5+/-8.2 vs. 15.9+/-6.1 mm s(-1), P<0.001). CONCLUSIONS: These data
      demonstrate that the position and function of the diaphragm is altered in CHF.

PMID- 11246056
TI  - Altered baroreflex gain during voluntary breathing in chronic heart failure.
AB  - BACKGROUND: We assessed the behavior of the baroreflex (BR) gain in chronic heart
      failure (CHF) patients using the spectral analysis method during application of a
      forcing stimulus, i.e. respiration. METHODS: Simultaneous RR interval and
      arterial pressure fluctuation recordings were obtained during two random-order
      periods of voluntary paced-breathing (0.15 Hz and 0.25 Hz) in seven patients with
      moderate CHF (NYHA class II/III; EF, 30+/-9%; peak VO(2), 18+/-5 ml kg(-1) min(
      1)) and six age-matched controls. BR gain was assessed in the time (sequential
      method) and frequency (cross-spectral gain in the low and high frequency)
      domains. RESULTS: Slower breathing was associated with a BR gain decrease in CHF
      patients whereas a BR gain increase was evidenced in controls (BR gain: 6+/-5 ms
      mmHg(-1) at 0.25 Hz vs. 4+/-3 ms mmHg(-1) at 0.15 Hz, P<0.05 in CHF; BR gain:
      12+/-7 ms mmHg(-1) at 0.25 Hz vs. 15+/-7 ms mmHg(-1) at 0.15 Hz, P<0.05 in
      controls). CONCLUSIONS: Voluntary breathing, which involves cortical centers in
      the brain, had major effects on cardiovascular system controller gain in CHF
      patients, indicating an impairment of the central neural regulation of the
      autonomic outflow.

PMID- 11246057
TI  - Different baseline sympathovagal balance and cardiac autonomic responsiveness in
      ischemic and non-ischemic congestive heart failure.
AB  - BACKGROUND: A profound autonomic unbalance is present in heart failure: its
      correlation with the etiology of the disease has never been investigated. AIMS:
      We characterized the sympatho-vagal balance and autonomic responsiveness of 42
      patients (21 with ischemic heart failure, 21 with idiopathic dilated
      cardiomyopathy). Patients had comparable NYHA class, ejection fraction, exercise
      pVO(2), exercise ventilatory response, incidence of beta-blocking treatment. None
      showed periodic breathing or nocturnal arterial desaturation. METHODS: Heart rate
      variability was assessed in the time and frequency domain during: (1) 10 min of
      quiet supine resting and free breathing; (2) 10 min of regular breathing at a
      frequency of 20 acts/min (=parasympathetic stimulus); and (3) 10 min of active
      standing (=sympathetic stimulus). The ratio of the low- to high-frequency
      components of each autospectrum obtained in the frequency domain (LF/HF) was used
      as an index of sympathovagal balance. RESULTS: Patients with ischemic heart
      failure had a greater baseline sympathetic activation (higher LF/HF) than those
      with idiopathic dilated cardiomyopathy, maintaining some parasympathetic
      responsiveness as well (reduced LF/HF with regular breathing). CONCLUSIONS: There
      is a distinct autonomic control according to the etiology of heart failure, a
      finding that may help understanding its pathophysiology, and could be useful in
      the clinical management of patients.

PMID- 11246058
TI  - Aspirin does not influence the effect of angiotensin-converting enzyme inhibition
      on left ventricular ejection fraction 3 months after acute myocardial infarction.
AB  - The aim of the present study was to evaluate the possible interaction between
      chronic aspirin therapy and angiotensin-converting enzyme inhibitor (ACE-I) on
      left ventricular ejection fraction (LVEF) in patients surviving an acute
      myocardial infarction (AMI). Forty-two patients with reduced LVEF were recruited
      from the warfarin aspirin reinfarction study (WARIS-II), a randomized, open study
      comparing enteric coated aspirin (160 mg/d), warfarin (INR 2.8--4.2) and the
      combination of aspirin (75 mg/d) and warfarin (INR 2.0--2.5) on mortality,
      reinfarction and stroke after AMI. LVEF and relevant biochemical measurements
      were performed before discharge and after 3 months. The overall LVEF increased
      during the study period from median 35 to 39% (P<0.001). There was no difference
      between patients on aspirin and warfarin regarding the main end point, LVEF.
      Furthermore, neither endothelin-1 nor ANP showed significant differences between
      the treatment groups. A possible interaction between ACE-I and aspirin might
      theoretically lead to reduced levels of renin activity in patients on aspirin,
      but we did not find any such inter-group difference. In conclusion, we did not
      find evidence of interaction between ACE-I and low-dose aspirin.

PMID- 11246059
TI  - Elimination of early rehospitalization in a randomized, controlled trial of
      multidisciplinary care in a high-risk, elderly heart failure population: the
      potential contributions of specialist care, clinical stability and optimal
      angiotensin-converting enzyme inhibitor dose at discharge.
AB  - BACKGROUND: Despite a growing body of data demonstrating the benefits of
      multidisciplinary care in heart failure, persistently high rates of readmission,
      especially within the first month of discharge, continue to be documented. AIMS:
      As part of an ongoing randomized study on the value of multidisciplinary care in
      a high risk (NYHA Class IV), elderly (mean age 69 years) heart failure
      population, we examined the effects of this intervention on previously high (20%)
      1-month readmission rates. METHODS: Unlike previous studies of this approach,
      both multidisciplinary (MC) and routine care (RC) populations were cared for by
      the cardiology service, complied with adherence to clinical stability criteria
      prior to discharge (100% of patients) and received at least target dose
      angiotensin-converting enzyme (ACE) inhibition with perindopril prior to
      discharge (94% of indicated patients). We analysed death and unplanned
      readmission for heart failure at 1 month. RESULTS: This early report from the
      first 70 patients (67% male, 71% systolic dysfunction with a mean ejection
      fraction of 31.0+/-6.7%) enrolled in this study demonstrates elimination of 1
      month hospital readmission in both RC and MC groups. This unexpected result
      represents a dramatic improvement both for this patient cohort (20% 30-day
      readmission rate prior to enrollment reduced to 0% following the index admission
      in both care groups) and in comparison with available data. CONCLUSIONS: Critical
      contributors to this improvement appear to be specialist cardiology care,
      adherence to clinical stability criteria prior to discharge and routine use of
      target or high-dose ACE inhibitor therapy prior to discharge. Widespread
      application of this approach may have a dramatic improvement in morbidity of CHF
      while limiting the escalating costs of this condition.

PMID- 11246060
TI  - Perceived benefit after participating in positive or negative/neutral heart
      failure trials: the patients' perspective.
AB  - BACKGROUND: Clinical trials, the gold standard for the evaluation of new
      therapeutic strategies, may prove a drug to be beneficial, harmful or neutral
      according to its effect on the end-point(s) under study. AIMS: To study the
      reaction and perspective of the patients participating in a clinical heart
      failure trial, particularly in relation to whether the trial subsequently proved
      to be positive, negative or neutral. METHODS: Anonymous self-completed
      questionnaire was sent to 78 and returned by 70 consecutive patients 1--6 months
      after participating in six clinical heart failure trials. The trial was neutral
      or negative regarding the primary end-point in four (47 patients) of the six
      studies (MACH-1 trial of mibefradil, REACH trial of bosentan, CASCO trial of
      calcium sensitizer, ecadotril trial of neutral endopeptidase inhibitor) and
      positive in two (23 patients) (ICARUS Israel carvedilol study, exercise study of
      candesartan cilexetil). RESULTS: Most patients reported subjective global
      clinical benefit (78% for positive, 74% for negative or neutral trial, NS) after
      participating in a clinical trial. After adjustment for age, sex, level of
      education, previous research, perceived comprehension, and treatment allocation
      (active drug/placebo) in a stepwise regression model, perceived global
      improvement was greater in older patients (P=0.02), after participation in a
      positive trial (P=0.05) and in females (P=0.07). The major reason given by the
      patient for perceived clinical improvement was better follow-up, some believed it
      was due to change in medication, particularly those who had participated in a
      positive trial. CONCLUSIONS: More than 70% of patients participating in clinical
      trials of new drugs for heart failure reported perceived global improvement.
      Clinical improvement was greater in, but not limited to, patients who
      participated in positive trials. These salutary findings support the continued
      recruitment of patients to clinical heart failure trials.

PMID- 11246061
TI  - Incidence of newly diagnosed heart failure in UK general practice.
AB  - AIM: To estimate the incidence rate of heart failure in the general population
      and to assess risk factors associated with the occurrence of newly diagnosed
      heart failure. METHODS: From the source population that was derived from the UK
      General Practice Research Database, we identified patients aged 40--84 years
      newly diagnosed with heart failure in 1996, and estimated incidence rates. We
      sent questionnaires to a random sample of heart failure patients (N=1200) and
      performed a nested case-control analysis to assess risk factors for heart
      failure. RESULTS: The overall incidence rate for heart failure was 4.4 per 1000
      person-years in men and 3.9 per 1000 person-years in women. The incidence
      increased steeply with age in both sexes. The relative risk of heart failure was
      2.1 (95% C.I.: 1.7--2.6) among men compared with women less than 65 years old and
      1.3 (95% C.I.: 1.2--1.4) above the age of 65. Slightly more than half of the
      cases were categorized in NYHA III--IV at the time of the first diagnosis. Within
      one month of initial diagnosis 62% of the men and 50% of the women were referred
      to specialists and/or hospitalized for heart failure. Smoking, hypertension,
      diabetes, obesity were independently associated with heart failure as well as
      history of distant dyspnoea. Coronary heart disease was the most common cause of
      heart failure with a greater relative prevalence in men than women. CONCLUSION:
      Incident heart failure cases mainly comprised elderly men and women frequently
      burdened with several diseases in general practice. Women had a lower incidence
      of heart failure than men. However, traditional risk factors such as smoking,
      hypertension, obesity, diabetes and dyspnoea appeared to confer the same relative
      increase in heart failure risk among women and men.

PMID- 11246063
TI  - Isolated diastolic heart failure as a cause of breathlessness in the community:
      the Arbroath study.
AB  - The aim of this study was to examine the prevalence of exercise limitation due to
      diastolic heart failure among patients felt to have cardiac breathlessness by
      their general medical practitioner but not referred to hospital. We found that
      18% of patients had a simple investigated profile compatible with isolated
      diastolic dysfunction as a cause of their symptoms. Symptoms appeared to pre-date
      major cardiac events (infarction; stroke; arrhythmia) that dominated the
      subsequent clinical course. The patients in this group have adverse
      cardiovascular risk profiles. Obesity was a common co-morbidity which may impair
      detailed 2-D echocardiographic assessment.

PMID- 11246064
TI  - Poles apart, but are they the same? A comparative study of Australian and
      Scottish patients with chronic heart failure.
AB  - This paper reports on an international comparison of the characteristics,
      treatment and health outcomes of chronic heart failure (CHF) patients discharged
      from acute hospital care in Australia and Scotland. The baseline characteristics
      and treatment of 200 CHF patients recruited to a randomised study of a non
      pharmacological intervention in Australia and 157 CHF patients concurrently
      recruited to a similar study in Scotland were compared. Subsequent health
      outcomes (including survival and readmission) within 3 months of discharge in
      those patients who received usual post-discharge care in Australia (n=100) and
      Scotland (n=75) were also compared. Individuals in both countries were
      predominantly old and frail with significant comorbidity likely to complicate
      treatment. Similar proportions of Australian and Scottish patients were
      prescribed either a 'high' (20 vs. 18%) or medium (64 vs. 66%) dose of an
      angiotensin-converting enzyme inhibitor. Proportionately more Australian patients
      were prescribed a long-acting nitrate, digoxin and/or a beta-blocker. At 3 months
      post-discharge, 57 of the 100 (57%: 95% CI 47--67%) Australian and 37 of the 75
      (49%: 95% CI 38--61%) Scottish patients assigned to 'usual care' remained event
      free (NS). Similarly, 15 vs. 12% required > or =2 unplanned readmission (NS) and
      16 vs. 19% of Australian and Scottish patients, respectively, died (NS).
      Australian and Scottish patients accumulated a median of 0.6 vs. 0.9 days,
      respectively, of hospitalisation/patient/month (NS). On multivariate analysis
      (including country of origin), unplanned readmission or death was independently
      correlated with severe renal impairment (adjusted odds ratio 4.4, P<0.05), a
      previous hospitalisation for CHF (2.3, P<0.05), longer index hospitalisation (2.7
      for >10 days, P<0.05) and greater comorbidity (1.3 for each incremental unit of
      the Charlson Index, P=0.05). Health outcomes among predominantly old and frail
      CHF patients appear to be independent of the health-care system in which the
      patient is managed and more likely to be dependent on the syndrome itself.

PMID- 11246062
TI  - Worsening of heart failure during hospital course of an unselected cohort of 2507
      patients with myocardial infarction is a factor of poor prognosis: the PRIMA
      study. Prise en charge de l'Infarctus du Myocarde Aigu.
AB  - Worsening of heart failure in patients with myocardial infarction is seldom
      studied, elderly patients often are not included, and multivariate analysis is
      uncommon. The prospective PRIMA study (Prise en charge de l'Infarctus du Myocarde
      Aigu; management of acute myocardial infarction) sought to determine the
      incidence of worsening heart failure, its risk factors, and its prognostic
      importance in patients with myocardial infarction, regardless of age and hospital
      facilities, in the 'real world' in a region in France, using multivariate
      analysis. Data were prospectively collected in all patients with myocardial
      infarction admitted in all hospitals in three departments in the Rhone--Alpes
      region in France between 1 September 1993 and 31 January 1995. Among the 2507
      patients included, 33% were in Killip classes II--IV at admission. After
      exclusion of patients with admission Killip class IV, 416 patients (17% of the
      cohort, 24% of women and 14% of men) had worsening of Killip class during the
      first 5 days. In-hospital mortality (overall, 14%) increased dramatically with
      Killip class at admission (9% in class I, 62% in class IV) and with worsening of
      Killip class during the first 5 days (36.5 vs. 8.5% if no worsening). In
      multivariate analysis, older age, diabetes mellitus and anterior Q-wave
      myocardial infarction were significant predictors of Killip class at admission
      and of its worsening; Killip class >I at admission was a significant predictor of
      Killip-class worsening. The significant predictors of in-hospital mortality were
      older age, Killip class III at admission and worsening of Killip class during the
      first 5 days. This large, unselected cohort revealed that, among patients with
      myocardial infarction, heart failure and its worsening are frequent, especially
      in the elderly, and dramatically worsen the in-hospital mortality.

PMID- 11246065
TI  - How patients with heart failure are managed in Italy.
AB  - In Italy, the National Health System is funded from the taxation system of the
      state. It is organized by general practitioners in the community and specialists
      in the hospitals. All Italian citizens are registered with one of the general
      practitioners. Patients with suspected heart failure are generally referred from
      the family practitioner to a higher level of medical care. Only a minority of
      patients with heart failure are cared for by cardiologists, either as in- or
      outpatients. Echocardiography is widely available; nevertheless, few patients
      admitted to internal medicine divisions receive an echocardiogram compared to
      cardiology units. The ACE inhibitor usage by Italian cardiologists in patients
      with heart failure is satisfied, and the use of beta blockers is increasing in
      Italy at this time. Since only a small proportion of patients with heart failure
      are followed by cardiologists in Italy, further efforts are necessary until
      internists and general practitioners could be involved in treatment trials in
      heart failure. The aim of this approach is to transfer the beneficial effects
      observed in the trials to clinical practice.

PMID- 11246066
TI  - Bacterial formyl peptide mediated chemotaxis and extracellular acidification in
      shrimp haemocytes.
AB  - The bacterial formyl peptide N-formylmethionine-leucine-phenylalanine (fMLP) is a
      potent chemoattractant for mammalian neutrophils. In this study, we demonstrated
      the binding of fluorescent dye-conjugated-fMLP to haemocytes of the penaeid
      shrimp Penaeus penicillatus (Alcock), through the use of flow cytometry.
      Fluorescence microscopy with rhodamine-fMLP suggested that fMLP receptors are
      present only in sub-populations of the haemocytes: granulocytes and the semi
      granular cells. In addition, fMLP dose-dependently mediated chemotaxis in sub
      populations of haemocytes. Microphysiometry experiments demonstrated rapid
      extracellular acidification upon addition of fMLP, which is in agreement with the
      observation in neutrophils. t-BOC, the specific fMLP receptor antagonist, was
      able to block the binding, chemotaxis and extracellular acidification induced by
      the peptide. The ability of shrimp haemocytes to migrate toward fMLP in vitro
      suggests that this mechanism may be important for the accumulation of these cells
      in infected tissues of the shrimps.

PMID- 11246067
TI  - Monoclonal antibodies against haemocyte molecules of Penaeus monodon shrimp react
      with haemolymph components of other crustaceans and disparate taxa.
AB  - In a previous study, monoclonal antibodies (mAbs) against different haemolymph
      molecules of the marine shrimp Penaeus monodon were produced and characterised.
      It was suggested that these mAbs could be used in studying haemocyte
      differentiation, behaviour and function in P. monodon. In the present study, the
      reaction of these mAbs on P. monodon was compared with other crustaceans and
      disparate taxa. The mAbs also reacted with haemolymph components of three
      freshwater crustaceans, a terrestrial isopod crustacean and with coelomic fluid
      of an annelid. No reactions were observed with haemolymph of an insect and a
      mollusc, nor with blood cells of two vertebrates. This comparative study shows
      reactivity of the mAbs with a wide range of crustaceans and related animals and
      suggests that well conserved molecules are recognised, which may indicate
      functional importance. Well-described mAbs can be used in studies of the
      crustacean defence system and may finally result in a better insight into this
      system.

PMID- 11246068
TI  - Noradrenaline modulates hemocyte reactive oxygen species production via beta
      adrenergic receptors in the oyster Crassostrea gigas.
AB  - Catecholamines (CA) are known to be present in the microenvironment of molluscan
      immunocytes. In the present study, experiments were conducted to determine the
      effects of noradrenaline (NA), the principal CA circulating in bivalve hemolymph,
      on the luminol-dependent chemiluminescence (CL) of oyster Crassostrea gigas
      hemocytes. Results show that NA had a dose-dependent inhibitory effect on the CL
      response at the physiological concentration of 0.1 microM and above. The alpha
      adrenoceptor agonist phenylephrine had no significant effect on the CL-response
      whereas the beta-adrenoceptor agonist isoproterenol mimicked the inhibitory
      effects of NA on the CL-response. The beta-adrenoceptor antagonist propanolol,
      but not the alpha-adrenoceptor antagonist prazosin, prevented the negative
      effects of NA on the CL-response. Taken together, these results show that beta
      adrenergic receptors are present at the surface of oyster hemocytes and allow NA
      to down-regulate the CL-response.

PMID- 11246069
TI  - Expression of immunoglobulin heavy chain transcripts (VH-families, IgM, and IgD)
      in head kidney and spleen of the Atlantic cod (Gadus morhua L.).
AB  - Expression of the immunoglobulin (Ig) heavy chain transcripts in spleen and head
      kidney of the Atlantic cod (Gadus morhua L.) was investigated using in situ
      hybridization (ISH) and northern blotting. Specific detection of plasma cells was
      done with a probe for secretory IgM transcripts (mu 4). The plasma cells were
      often clustered close to blood vessels. Cells expressing surface IgM and IgD
      transcripts were detected using ISH with tyramide signal amplification (TSA). The
      positive cells were more abundant than plasma cells, had a lymphocyte-like
      morphology, and were evenly distributed throughout the tissues. This suggests
      that cod IgD mainly is expressed as a B-cell receptor akin to IgD in mammals. The
      VH-III family dominated the repertoire within the plasma cells, in agreement with
      data from cDNA cloning. Immunization with hapten-carrier antigen did not induce a
      systemic antibody response, and neither was any change in the clustering or
      distribution pattern of plasma cells within the tissues seen. A few clusters of
      plasma cells expressed only the rare VH-I and VH-II families, suggesting an
      ongoing clonal expansion and differentiation in these regions independently of
      immunization.

PMID- 11246070
TI  - Cloning and sequencing of caspase 6 in rainbow trout, Oncorhynchus mykiss, and
      analysis of its expression under conditions known to induce apoptosis.
AB  - The rainbow trout caspase 6 gene has been cloned and sequenced. The open reading
      frame consisted of 906bp, which translated into a protein of 302 amino acids,
      containing the caspase active site pentapeptide (QACRG) and the caspase family
      signature (HADADCFVCVFLSHG). Amino acids involved in catalysis and those known to
      form the P1 carbohydrate binding pocket were conserved. Phylogenetic tree
      analysis showed a tight grouping with other known caspase 6 genes. Conserved
      aspartic acid residues at positions 33, 191 and 202 suggested that this molecule
      is produced as a proenzyme that is subsequently cleaved to release active
      subunits, with the region between Asp-191 and Ala-203 acting as a linker that is
      cleaved out. RT-PCR analysis revealed that the trout caspase 6 gene was expressed
      in brain, blood, gill, liver, head kidney and spleen. Addition of LPS or cortisol
      to head kidney leucocyte cultures had no effect upon caspase 6 expression.
      However, addition of LPS after preincubation with cortisol increased expression
      relative to control cultures. Incubation with RU486 abrogated this effect,
      confirming it was mediated via glucocorticoid receptors. Lastly, a confinement
      stress in vivo increased caspase 6 expression. The data are discussed with
      respect to the immunoregulatory role of apoptosis in fish immune responses.

PMID- 11246071
TI  - CpG oligodeoxynucleotides and plasmid DNA stimulate Atlantic salmon (Salmo salar
      L.) leucocytes to produce supernatants with antiviral activity.
AB  - Unmethylated CpG dinucleotides are more frequent in the genomes of bacteria and
      viruses than of vertebrates. We report herein that plasmid DNA and synthetic
      oliogodeoxynucleotides (ODNs) containing unmethylated CpG induce production of
      antiviral cytokine activity in Atlantic salmon leucocytes, whereas ODNs with an
      inverted motif (GpC) or with methylated cytosines have nearly no stimulatory
      effect. The adherent cell population, representing mainly macrophages, is
      directly activated by CpG-ODN, while the effect on the non-adherent population is
      weak. Since the peak antiviral activity in ODN-stimulated leucocytes is seen
      after 48h, this might indicate that the unmethylated DNA stimulates the adherent
      cells to produce co-stimulatory molecules, which in turn stimulates production of
      antiviral cytokines in the non-adherent cell population. The potent immune
      activation by CpG ODNs points to possible new applications as adjuvant in fish
      vaccines.

PMID- 11246072
TI  - In vitro thymocyte differentiation in MHC class I-negative Xenopus larvae.
AB  - CTX is a surface antigen whose expression in larval and adult Xenopus is
      primarily restricted to MHC class I-negative immature cortical thymocytes. In
      adult Xenopus, surface expression of CTX marks a population of MHC class I(-)
      CD8(+) immature thymocytes that appears to be the equivalent of the mammalian
      CD4CD8 double positive subset. The present study reveals that transient in vitro
      exposure of immature CTX(+) thymocytes from MHC class I-negative tadpoles to
      suboptimal mitogenic concentrations of phorbol ester (PMA) plus ionomycin,
      induces larval cells to differentiate into more mature T-lymphoblasts that
      express high level of surface CD5 and CD45. These T-lymphoblasts have
      downregulated CTX, Rag 1 and TdT genes, whereas TCR-beta genes remain actively
      transcribed. Signaling induced by PMA/ionomycin modulates both class I and class
      II expression of MHC class I/II-negative larval thymocytes. This study also
      reveals that larval T-lymphoblasts are composed of two distinct subsets:
      CD5(high)CD8(-) and CD5 (high)CD8 (high).

PMID- 11246073
TI  - Evidence for the direct action of thymulin on avian NK cells.
AB  - The ability of thymulin to directly enhance NK cell-mediated cytotoxicity was
      examined. Specific cell population depletions were done in K and SLD chicken
      splenocyte preparations using anti-CD3, CD4, and CD8 monoclonal antibodies and
      secondary complement-fixing polyclonal antibodies. The remaining cells were
      incubated overnight with in vitro treatments of thymulin and IFN-gamma, either
      separately or together, followed by an assay for cytotoxicity. Although the
      control K-strain had higher overall NK cell-mediated cytotoxicity than the
      thymulin-deficient SLD-strain, the following trends were seen in both strains.
      Thymulin continued to enhance NK activity following CD4 or CD3 cell depletion,
      but not after CD8 or CD8 and CD4 cell depletion. Since avian NK cells express CD8
      alpha, but not CD3 or CD4 on their surface, these results suggest that the
      ability of in vitro thymulin treatments to enhance NK activity is not mediated by
      T-cells but may be due to direct effects on NK cells.

PMID- 11246074
TI  - Soluble type-I interleukin-1 receptor blocks chicken IL-1 activity.
AB  - The ligand-binding domain of the chicken type-I interleukin-1 (IL-1) receptor
      (soluble IL-1R(I); sIL-1R(I)) was cloned into a Pichia pastoris expression system
      and the resulting sIL-1R(I) binding protein was used to produce antisera in
      rabbits (anti-IL-1R(I)). Two experiments were conducted to determine the capacity
      of sIL-1R(I) or anti-IL-1R(I) to block the IL-1 bioactivity (thymocyte co
      stimulation) in conditioned media (CM) from HD11 chicken macrophages stimulated
      with lipopolysaccharide. In the first experiment, pre-incubation of CM with
      unpurified sIL-1R(I) significantly decreased its thymocyte co-stimulation
      activity by 57%. Further purification of sIL-1R(I) from other proteins secreted
      or shed from P. pastoris expression system by size exclusion filtration or
      ammonium sulfate (60%) precipitation did not influence its capacity to neutralize
      IL-1 bioactivity. These partially purified sIL-1R(I) preparations significantly
      decreased thymocyte co-stimulation activity in CM by 70.7 and 77.3%,
      respectively. In the second experiment, pre-incubation of thymocytes with
      antisera against the sIL-1R(I) decreased IL-1 activity in CM by 70% relative to
      control thymocyte cultures that received no antibody and by 59% relative to
      thymocyte cultures incubated with pre-immune sera. Presumably anti-sIL-1R(I)
      diminished the IL-1 bioactivity in CM by blocking IL-1 binding to its type-I
      receptor on thymocytes. Thus, 30% of the IL-1-like activity released by LPS
      stimulated HD11 macrophages is probably due to at least one other cytokine. Our
      data are consistent with the type-I receptor being the primary IL-1 receptor on
      chicken thymocytes that is capable of providing a signal for proliferation.

PMID- 11246075
TI  - Convulsive therapy: a review of the first 55 years.
AB  - Convulsive therapy was introduced to psychiatric practice in 1934. It was widely
      hailed as an effective treatment for schizophrenia and quickly recognized as
      equally effective for the affective disorders. Like other somatic treatments, it
      was replaced by psychotropic drugs introduced in the 1950s and 1960s. But two
      decades later, ECT was recalled to treat pharmacotherapy-resistant cases. Avid
      searches to optimize seizure induction and treatment courses, to reduce risks and
      fears, to broaden the indications for its use, and to understand its mechanism of
      action followed. Unlike other medical treatments, however, these searches were
      severely impeded by a vigorous antipsychiatry movement among the public and
      within the profession. ECT is effective in the treatment of patients with major
      depression, delusional depression, bipolar disorder, schizophrenia, catatonia,
      neuroleptic malignant syndrome, and parkinsonism, and this breadth of action is
      both remarkable and unique. ECT is a safe treatment. No age or systemic condition
      bars its use. Its major limitations are the high relapse rates and the occasional
      profound effects on memory and recall that mar its success. Experiments to
      sustain its benefits with medications and with continuation ECT are underway. Its
      mode of action remains a mystery and this puzzle is an unappreciated challenge.
      The full impact of this intervention is yet to be felt.

PMID- 11246076
TI  - Electroconvulsive therapy is associated with superior symptomatic and functional
      change in depressed patients after psychiatric hospitalization.
AB  - BACKGROUND: Major depressive episode is associated with quality of life (QOL)
      deficits, and QOL improves following remission of depression. We conducted an
      observational study of the relationship between depressive symptoms and QOL for 1
      year after psychiatric hospitalization, and compared QOL in patients who received
      ECT against those who did not. METHODS: We examined 88 patients with major
      depressive disorder (53.4+/-15.4 years old; 69 women) upon admission, with
      repeated measurements at discharge, 1, 3, 6, and 12 months after discharge.
      Depression severity was measured with the Beck Depression Inventory. QOL
      measurements encompassed ADLs, IADLs, performance in major roles, and
      satisfaction with relationships. Treatment for depression was at the discretion
      of the respective physicians. RESULTS: Depression severity dropped dramatically
      by discharge, and changed little thereafter. QOL measures showed improvement at
      the first month, with additional improvement at the third month. Improvement in
      QOL was closely tied to improvement in depression severity. ECT during the index
      hospitalization was associated with greater improvement in depressive symptoms
      and in most measures of QOL. LIMITATIONS: The results of this study may not apply
      to the treatment of outpatients, and the large number of statistical comparisons
      may have resulted in some spurious associations. CONCLUSIONS: Inpatient treatment
      of depression is followed by improvement in QOL. Novel findings in this study
      include evidence that maximum improvement in QOL does not occur until an average
      of 3 months after discharge, and that ECT-treated patients had superior outcomes.

PMID- 11246077
TI  - Immune-inflammatory markers in patients with seasonal affective disorder: effects
      of light therapy.
AB  - BACKGROUND: There is increasing evidence that an activation of the immune
      inflammatory system is involved in the pathophysiology of depressive disorders.
      The purposes of this study were to (1) compare immune-inflammatory markers in
      patients with seasonal affective disorder (SAD) with those in matched normal
      controls; and (2) examine the effects of light therapy on the immune-inflammatory
      markers in patients with SAD. METHODS: Plasma concentrations of interleukin-6 (IL
      6), soluble IL-6 receptor (sIL-6R) and soluble IL-2 receptor (sIL-2R) were
      measured in 15 patients with SAD and 15 age- and sex-matched normal controls. Of
      the 15 patients, 14 had repeated blood sampling for these variables following 2
      weeks of light therapy. RESULTS: We found that patients with SAD had
      significantly increased IL-6 levels compared to normal controls (P<0.0005). There
      was a trend toward increased sIL-2R in patients with SAD (P=0.09). There was no
      significant difference in sIL-6R level between the two diagnostic groups
      (P=0.18), but the product term (IL-6xsIL-6R) was significantly higher in patients
      with SAD than that in normal control controls (P<0.0003). Furthermore, all 14
      patients who completed the study improved with 2 weeks of light therapy and nine
      of them (64%) had 50% reduction in score of the Hamilton Depression Rating Scale
      SAD version post-treatment compared to baseline. However, the initially increased
      immune markers in SAD patients were not significantly altered by the therapeutic
      light therapy. LIMITATIONS: This study was limited to a small sample size and
      other immune inflammatory markers should be measured for further evidence of
      immune activation in seasonal depression. CONCLUSIONS: Our results of increased
      IL-6, IL-6xsIL-6R, and sIL-2R in patients with SAD suggest an activation of the
      immune-inflammatory system in winter depression, which is not altered by 2 weeks
      of successful light therapy.

PMID- 11246078
TI  - Long-term medical conditions and major depression in a Canadian population study
      at waves 1 and 2.
AB  - BACKGROUND: Cross-sectional studies have reported that certain long-term medical
      conditions are associated with major depression. Here, these associations are
      explored using a longitudinal analysis. METHODS: Data from the first (1994/95)
      and second (1996/97) waves of the Canadian National Population Health Survey
      (NPHS) were utilized. The first wave of the NPHS utilized a probability sample of
      17626 members of the Canadian population. Members of this cohort were recontacted
      by Statistics Canada 2 years later. The Composite International Diagnostic
      Interview Short Form for Major Depression was used to identify episodes of major
      depression in both waves of the survey. Subjects free of major depression in the
      year preceding the 1994/95 survey were selected for inclusion in this analysis.
      The incidence of new-onset episodes in subjects with and without reported long
      term medical conditions was compared. RESULTS: Individuals suffering from one or
      more long-term medical conditions were found to be at increased risk of major
      depression. Migraine headaches, sinusitis and back problems were the conditions
      most strongly associated with major depression. Having a long-term medical
      condition approximately doubled the risk of major depression in this analysis.
      LIMITATIONS: The most important limitation of this study was its reliance on self
      report data about medical conditions. CONCLUSIONS: A large proportion of the
      general population in Canada suffers from long-term medical conditions. These
      individuals are at increased risk of major depression. This study suggests an
      important role for long-term medical conditions in the etiology of major
      depression.

PMID- 11246079
TI  - Expressed emotion of families and the course of mood disorders: a cohort study in
      Japan.
AB  - BACKGROUND: Findings on expressed emotion (EE) of the family and the course of
      mood disorders have not been consistent. There has also been no report on these
      problems from Asia. METHODS: The subjects were 32 patients diagnosed to have mood
      disorders on the basis of DSM-IV and ICD-10 and 36 principal members of their
      families. EE was evaluated using Camberwell Family Interview (CFI). A cohort
      study was conducted for 9 months after discharge of the patients. The patients
      were divided into a high-EE group and a low-EE group using a few cut-off points
      concerning the number of critical comments (CCs) and emotional over-involvement
      (EOI), the 9-month relapse risks were compared, and the relapse risk ratio and
      its 95% confidence interval were calculated. Also, the sensitivity, specificity,
      positive predictive value, and negative predictive value were calculated, and the
      optimal cut-off point was evaluated. Multiple logistic regression analysis was
      performed to control the effects of potential confounding factors. RESULTS: When
      the subjects with three or more CCs, or an EOI score of three or higher were
      regarded as a high-EE group, and the others as a low-EE group, the nine-month
      relapse risks were 83.3% (5/6) and 19.2% (5/26), respectively, and the relapse
      risk ratio (95% confidence interval) was 4.3 (1.8-12.2). The values of the
      validity parameters were the highest with these cut-off points. The effect of EE
      was also significant on multiple logistic regression analysis. LIMITATIONS: Small
      sample size and severity of the patients. CONCLUSIONS: Families' EE based on CFI
      correlated with relapse also in Japan.

PMID- 11246080
TI  - Subsyndromal depression in adolescents after a brief psychotherapy trial: course
      and outcome.
AB  - INTRODUCTION: Subsyndromal depression has been associated with an increased risk
      of the development of major depressive disorder (MDD). Since treatment trials of
      adolescent MDD often result in subsyndromal depression as the outcome, the long
      term course of these youth would be useful to understand. METHODS: 107
      adolescents with MDD participated in a clinical psychotherapy trial, of whom 99
      were followed up for two years after acute treatment. Those with subsyndromal
      depression (2-3 symptoms) at the end of acute treatment were compared to those
      who were well (< or =1 symptom) and those who were still depressed (> or =4
      symptoms) on presentation at intake, the end of treatment, and over the two-year
      follow-up. RESULTS: Of the 99 youth, at the end of acute treatment 26 were well,
      18 were subsyndromal, and 55 were still depressed. A substantial proportion of
      the subsyndromally depressed youth were functionally impaired (38%), and showed a
      protracted time to recovery. The risk of recurrence was similar to those who were
      without depression at the end of acute treatment (46% vs. 44%). Recurrence was
      predicted by depressive symptom severity and family difficulties at the end of
      acute treatment. LIMITATIONS: A large proportion of the subsyndromal groups
      received open treatment that may have altered their course. Also, this was a
      referred sample, rather than an epidemiological one. CONCLUSIONS: In clinical
      samples treated with psychotherapy, subsyndromal depression poses a significant
      risk for functional impairment and protracted recovery. Depressive recurrence may
      be prevented by targeting reduction of symptom severity and of family
      difficulties.

PMID- 11246081
TI  - Suicidal thoughts and attempts among adolescents: a longitudinal 8-year follow-up
      study.
AB  - BACKGROUND: To study the prevalence of and factors associated with suicidal
      behaviour among 580 adolescents. METHODS: An 8-year longitudinal study included
      questions about suicidal attempts and thoughts at age 16. Children were evaluated
      with parent and teacher Rutter scales and self-reported Child Depression
      Inventory at age 8. At age 16, parents filled in the Child Behaviour Check List
      and adolescents the Youth Self Report. RESULTS: 14% of girls and 7% of boys
      reported suicidal thoughts or preoccupations at age 16. Emotional and behavioural
      problems at age 8, especially antisocial symptoms, reported by parents and
      teachers and depressive symptoms reported by the child were correlated with
      suicidal thoughts and behaviour 8 years later. At age 16, internalizing and
      externalizing problems and low social competence were associated with suicidal
      features. Only about 20% of those who reported suicidal features had been
      referred to child mental health services. CONCLUSIONS: Many adolescents with
      suicidal thoughts and behaviour had a high rate of behavioural and emotional
      problems already at age 8. CLINICAL IMPLICATIONS: The early school years
      represent an opportunity for interventions which may prevent self-destructive
      behaviours in adolescence.

PMID- 11246082
TI  - Personality and outcome in depression: an 18-month prospective follow-up study.
AB  - BACKGROUND: The relationship between personality and depressive illness is
      complex. The aim of this study was to assess whether the presence of a
      personality disorder or high neuroticism (N) scores predicted longer times to
      discharge or remission onset or higher risks of relapse for a cohort of depressed
      subjects admitted for the first time. METHODS: 100 consecutive subjects with ICD
      10-defined depression were recruited on admission and followed up prospectively
      over an 18-month period. Personality function was rated using the informant-rated
      Standard Assessment of Personality in addition to the self-rated Maudsley
      Personality Inventory. Remission onset and relapse were defined operationally by
      scores on the Hamilton Rating Scale using recommended criteria. RESULTS: The
      presence of a personality disorder predicted longer times to remission onset.
      Personality trait accentuation did not. Higher end N-scores correlated with
      longer times to remission onset. Neither personality disorder nor high N-scores
      predicted relapse or discharge risk. Subjects with a personality disorder were
      treated as aggressively as those without but those with higher N-scores were not.
      LIMITATIONS: It is an in-patient sample. Fifteen subjects dropped out of follow
      up and those who did so were more likely to have met criteria for two or more
      personality disorder categories or four or more traits from one personality
      disorder category. The analysis assumes that state and scar effects on N-scores
      were minimised. Treatment decisions were not controlled. CONCLUSIONS: These
      findings support the view that the presence of a personality disorder and high N
      scores modify the short-term course to remission onset in depression.

PMID- 11246083
TI  - Mood-stabilisers reduce the risk of developing antidepressant-induced maniform
      states in acute treatment of bipolar I depressed patients.
AB  - BACKGROUND: The aim of this study was to give further support to the available
      evidence that mood stabilizers can reduce the risk of antidepressant-induced
      maniform switch phenomena in bipolar I depressed patients. METHODS: Medical
      records of 158 patients with bipolar I depression were analysed for the incidence
      of switch phenomena from depression to maniform states (mania and hypomania). The
      impact of mood stabilizers on reducing the risk of switching was analyzed using
      logistic regression analyses. RESULTS: Maniform switches during inpatient
      treatment were observed in 39 (25%) patients out of the total of 158 patients.
      Results indicate that especially patients receiving tricyclic antidepressants are
      at risk of switching to maniform states. This risk was shown to be significantly
      less when patients also received a mood stabilising medication (lithium,
      carbamazepine or valproic acid). LIMITATIONS: This was a retrospective study with
      patients receiving naturalistic treatment. A prospective, double-blind design
      would probably lead to more conclusive findings. CONCLUSIONS: Treatment with mood
      stabilizers may be a potent strategy to reduce the risk of antidepressant-induced
      maniform switches in bipolar I depressed patients.

PMID- 11246084
TI  - The inflammatory response following delivery is amplified in women who previously
      suffered from major depression, suggesting that major depression is accompanied
      by a sensitization of the inflammatory response system.
AB  - BACKGROUND: There is now evidence that some patients with major depression show
      an activation of the inflammatory response system (IRS). This study was carried
      out to examine whether major depression may induce sensitization with increased
      IRS responses to the stress of child birth. METHODS: Serum concentrations of
      interleukin-6 (IL-6), the soluble IL-6 receptor (sIL-6R), sgp130 (the IL-6 signal
      transducing protein) and the sIL-1R antagonist (sIL-1RA) were determined in 16
      and 50 women with and without a lifetime history of major depression,
      respectively. Blood was collected 3-6 days before delivery and 1 and 3 days after
      delivery. On each occasion the women completed the Zung Depression Rating Scale
      (ZDS). RESULTS: Serum IL-6, sIL-6R, sIL-1RA were significantly higher 1 and 3
      days after delivery than before. Women who had suffered from a lifetime history
      of major depression had greater increases in serum IL-6 and sIL-1RA in the early
      puerperium than women without a lifetime history. Women who had suffered from a
      lifetime history of major depression had significantly higher IL-6, and sIL-1RA
      concentrations 1 and 3 days after delivery than women with a negative life-time
      history. CONCLUSIONS: The responses of IL-6 and sIL-1RA following delivery are
      amplified in women who previously suffered from major depression. The results
      suggest that major depression is accompanied by a sensitization of the IRS.

PMID- 11246085
TI  - Inflammatory markers in major depression and melancholia.
AB  - BACKGROUND: There is evidence that patients with major depression (MD) also
      suffer an inflammatory immune reaction. However, the results remain ambiguous.
      This could be due to the psychiatrically heterogeneous patient samples
      investigated in many published studies. Since melancholic depression is
      psychopathologically and possibly etiologically different from non-melancholic
      MD, we focused on investigating immune parameters in these two subgroups.
      METHODS: 43 in-patients suffering from acute major depression were diagnosed, sub
      classified according to DSM IV criteria, and compared to 43 matched healthy
      controls. Cell counts were determined by morphology, and acute phase proteins [c
      reactive protein (CRP), alpha(2)-macroglobulin (A2M), haptoglobin (HP)] were
      measured by laser nephelometry. Cytokine production (IL-1beta) upon mitogen
      stimulation was measured by ELISA in a whole blood assay. RESULTS: Non
      melancholic patients showed increased monocyte counts and A2M serum
      concentrations in the acute stage of disease and after 2 and 4 weeks of
      treatment. Melancholic patients demonstrated a decreased monocyte count upon
      admission and after 4 weeks of treatment. HP levels and IL-1beta production were
      unchanged in all studied subjects. LIMITATIONS: Medication of the patients
      varied. The differentiation between melancholic and non-melancholic depression
      was performed clinically and was not performed using any standardized instrument.
      CONCLUSION: Melancholic and non-melancholic patients show different immune
      patterns. This differentiation might clarify immunological findings in MD and
      point towards etiological factors that are involved in the development of various
      subtypes of MD.

PMID- 11246087
TI  - Risk and preventive factors of post-traumatic stress disorder (PTSD): alcohol
      consumption and intoxication prior to a traumatic event diminishes the relative
      risk to develop PTSD in response to that trauma.
AB  - BACKGROUND: Previous reports examined the effects of selected pre- (e.g. female
      gender, previous trauma), peri- (e.g. the horror of the trauma, threatened death)
      or post-exposure (e.g. the physical injury caused by the trauma) risk factors on
      the development of post-traumatic stress disorder (PTSD), an anxiety disorder
      associated with a traumatic event outside the range of usual human experience. We
      hypothesized that alcohol consumption prior to traumatic events may reduce the
      incidence rate of PTSD. The aim of this study was to examine the effects of the
      above risk factors and preventive factors, such as alcohol consumption, on the
      development of PTSD. METHODS: An epidemiological cohort study was carried out on
      127 victims trapped in a ballroom fire. Data were collected, 7-9 months after the
      traumatic event, by means of the Composite International Diagnostic Interview
      (CIDI) and structured interviews, aimed to assess the above pre-, peri- and post
      exposure factors. Logistic regression analysis was used to examine the
      association of PTSD with the etiologic factors and to delineate those risk
      factors which contribute most to the development of PTSD. RESULTS: Female gender,
      the number of previous trauma, a past history of simple phobia, threatened death,
      trauma exposure, hospitalization for trauma-induced injuries and the presence of
      burns increased the odds of PTSD, whereas a sense of control during the trauma,
      and alcohol consumption and intoxication decreased the odds of PTSD. Six factors
      made independent contributions to the prediction of PTSD, i.e. the number of
      previous trauma, a past history of simple phobia, loss of control (increase the
      odds), a sense of control, alcohol consumption and alcohol intoxication (decrease
      the odds). CONCLUSIONS: The results of this study show that the development of
      PTSD is determined by the effects of pre-, peri- and post-exposure risk factors
      and may be prevented by the effects of peri-traumatic factors, such as sense of
      control, alcohol consumption and intoxication.

PMID- 11246086
TI  - Can personality traits predict increases in manic and depressive symptoms?
AB  - BACKGROUND: There has been limited research investigating personality traits as
      predictors of manic and depressive symptoms in bipolar individuals. The present
      study investigated the relation between personality traits and the course of
      bipolar disorder. The purpose of this study was to identify specific personality
      traits that predict the course of manic and depressive symptoms experienced by
      bipolar individuals. METHODS: The sample consisted of 39 participants with
      bipolar I disorder assessed by the Structured Clinical Interview for DSM-IV.
      Personality was assessed using the NEO Five-Factor Inventory. The Modified
      Hamilton Rating Scale for Depression and the Bech-Rafaelsen Mania Rating Scale
      were used to assess symptom severity on a monthly basis. RESULTS: Consistent with
      previous research on unipolar depression, high Neuroticism predicted increases in
      depressive symptoms across time while controlling for baseline symptoms.
      Additionally, high Conscientiousness, particularly the Achievement Striving
      facet, predicted increases in manic symptoms across time. LIMITATIONS: The
      current study was limited by the small number of participants, the reliance on a
      shortened version of a self-report personality measure, and the potential state
      dependency of the personality measures. CONCLUSIONS: Specific personality traits
      may assist in predicting bipolar symptoms across time. Further studies are needed
      to tease apart the state-dependency of personality.

PMID- 11246088
TI  - Seasonal depression: the dual vulnerability hypothesis revisited.
AB  - OBJECTIVE: In DSM-IV, winter seasonal affective disorder (SAD) is classified as a
      seasonal pattern of recurrent major depressive episodes in winter with full
      remission of symptoms in summer. However, other groups with "winter depression"
      have been identified, including patients with incomplete summer remission (ISR)
      and subsyndromal SAD (sub-SAD, winter depressive symptoms that do not meet
      criteria for major depression). In this study, we compare the clinical
      characteristics of these three seasonal groups and their response to light
      therapy. METHOD: 558 patients assessed at a specialized SAD Clinic were diagnosed
      using DSM-III-R or DSM-IV criteria. Clinical information was recorded using a
      checklist at index assessment. A subset of patients (N=192) were treated with an
      open, 2 week trial of light therapy using a 10000 lux fluorescent light box for
      30 min per day in the early morning. Patients were assessed before and after
      treatment with the 29 item modified Hamilton Depression Rating Scale and clinical
      response was defined as greater than 50% improvement in scores. RESULTS: The
      rates of some melancholic symptoms, anxiety, panic, suicidal ideation, and family
      history of mood disorder were lowest in the sub-SAD group. The clinical response
      rates to light therapy were highest in the sub-SAD group (N=32, 78%),
      intermediate in the SAD group (N=113, 66%), and lowest in the ISR group (N=47,
      51%). LIMITATIONS: This was a retrospective study of patients seen in a specialty
      clinic, although information was obtained in a standardized format. The light
      therapy trial had an open design so that placebo response could not be
      determined. CONCLUSIONS: There are differences in both the patterns of clinical
      symptoms and the response to light therapy in these three groups with winter
      depression. These results are consistent with a dual vulnerability hypothesis
      that considers these groups to result from interaction of separate factors for
      seasonality and depression.

PMID- 11246089
TI  - Beyond the Winokur concept of depression spectrum disease: which types of
      alcoholism are related to primary affective illness?
AB  - BACKGROUND: This study explored the familial relationship between alcoholism and
      depression. The familial prevalence of major depression and alcoholism among
      alcoholic probands and controls was examined. METHOD: Alcoholic patients were
      classified on the basis of absence or presence of major depression preceding or
      following alcohol dependence. Research Diagnosis Criteria (RDC) family history
      method was performed on 62 males and 49 females with alcohol dependence, on 50
      healthy controls and on first degree relatives from all subjects. RESULTS: Female
      alcoholics had most commonly primary depression (74%) and alcoholic men had
      predominantly pure alcoholism (55%) and alcoholism with secondary depression
      (29%). Subjects with comorbid alcoholism and depression had earlier onset of
      alcohol dependence. The first degree relatives of probands with primary
      depression and secondary alcoholism had greater risk of alcoholism compared with
      the relatives of probands with alcoholism and secondary depression and with the
      relatives of pure alcoholics. In families of probands with primary depression and
      secondary alcoholism, increased prevalence of depression was observed.
      LIMITATION: The study has a relatively small population and only family history
      method to collect familial data of alcoholism and depression was used.
      CONCLUSION: Our results support Winokur's depressive spectrum hypothesis from
      another perspective. In our sample, male and female probands with primary
      depression and secondary alcoholism had the highest familial prevalence of both
      alcoholism and depression.

PMID- 11246090
TI  - Delta sleep EEG in depressed adolescent females and healthy controls.
AB  - BACKGROUND: Quantitative EEG studies have identified a number of sleep
      abnormalities in adults with major depressive disorders (MDD), including a
      reduction in the amplitude of delta activity during NREM sleep. To date, these
      methodologies have not been used in early onset MDD. METHODS: Delta activity
      during NREM sleep was compared in eight symptomatic but unmedicated adolescent
      females with MDD and eight age- and gender-matched healthy controls. RESULTS: The
      depressed group showed significantly lower delta amplitude and power in the first
      NREM sleep period. By contrast, standard sleep architecture did not differentiate
      between groups. LIMITATIONS: Given the sample size, this study is best viewed as
      tentative. In addition, it has yet to be determined whether adolescent males with
      MDD also show delta sleep abnormalities. Further, failure to find between-group
      differences in REM latency or other macroarchitectural measures may be due to the
      small sample size. CONCLUSIONS: The findings of this study underscore the utility
      of quantitative sleep EEG techniques in early onset MDD. The results of the
      present study do, however, diverge from reports in adults with MDD, where delta
      abnormalities are more prevalent in men. Such findings suggest that the
      maturational time course of sleep EEG disturbances may differ for males and
      females with depression. Early emergence of delta abnormalities in depression may
      be of relevance to clinical course of illness.

PMID- 11246091
TI  - Is gender a factor in psychiatrists' evaluation and treatment of patients with
      major depression?
AB  - BACKGROUND: Gender differences in clinical assessment and treatment have been
      reported in several areas of medicine. We examine whether differences exist in
      the routine outpatient psychiatric management of men and women with major
      depression. METHODS: Psychiatrists practicing in the community completed case
      forms on a systematic sample of their adult outpatients with major depression.
      Comparisons are presented between male (n=261) and female (n=472) patients
      focusing on their background characteristics, clinical presentation, assessment,
      and treatment. Significant gender disparities in assessment and treatment are
      also examined with respect to the gender of the treating psychiatrist. RESULTS:
      Although male and female patients had generally similar clinical profiles, a
      significantly greater proportion of males than females had psychomotor
      retardation and substance use disorders. No significant gender differences were
      observed in the assessment of depressive symptoms, psychiatric comorbidities, and
      treatment with antidepressant medications or psychotherapy. However, a
      significantly smaller percentage of depressed women than men received assessments
      of sexual function and medication-related sexual side effects. Female patients
      were also less likely to have discussed their treatment preferences with their
      psychiatrists. LIMITATIONS: Only a minority (33.2%) of psychiatrists invited to
      participate contributed patients to this study. The results are based on
      structured assessments completed by practicing psychiatrists rather than patient
      self-assessments or independent research assessments. CONCLUSIONS: Although we
      find overall little evidence of gender bias in the clinical management of major
      depression, both male and female psychiatrists need to further explore sexual
      function and treatment preferences in female patients.

PMID- 11246092
TI  - Suicide in young people aged 15-24: a psychological autopsy study.
AB  - BACKGROUND: The suicide rate in young people in the United Kingdom has increased
      over the last decade. As there is a paucity of information about the
      characteristics of young suicides we have undertaken a detailed investigation of
      suicides in people aged 15-24 years by means of the psychological autopsy
      approach. METHODS: The sample consisted of 27 subjects (25 males, two females)
      whose deaths received a verdict of suicide (N=24) or undetermined cause (N=3).
      Information was collected from informant interviews, coroners' inquest notes,
      medical records and psychiatric case notes. A sub-sample of 22 male subjects was
      compared with an age-matched sample of male deliberate self-harm (DSH) patients.
      RESULTS: Psychiatric disorders were diagnosed in 19 (70.4%) subjects. These were
      most commonly depressive disorders (55.5%). Very few individuals were receiving
      treatment for their disorders. Substance abuse disorders were uncommon but a
      substantial proportion of individuals had problems with alcohol or drug misuse.
      Personality disorders were present in 29.6% of subjects and disorders or
      personality trait accentuation in 55.6%. Comorbidity of psychiatric disorders was
      found in a third of subjects. The suicides were often the end-point of long-term
      difficulties extending back to childhood or early adolescence. In addition to
      mental disorders, relationship and legal difficulties were identified as
      relatively common contributory factors to the suicides. In comparison to
      deliberate self-harm patients, male suicides were more likely to use dangerous
      methods and live alone. LIMITATIONS: Several potential informants could not be
      interviewed and there was no general population control sample. CONCLUSIONS: The
      process leading to suicide in young people is often long term, with untreated
      depression in the context of personality and/or relationship difficulties being a
      common picture at the time of death. The prevention of suicide in the young
      clearly requires multiple strategies.

PMID- 11246093
TI  - Prolonged desipramine treatment increases the production of interleukin-10, an
      anti-inflammatory cytokine, in C57BL/6 mice subjected to the chronic mild stress
      model of depression.
AB  - BACKGROUND: Depression is associated with activation of the inflammatory response
      system (IRS). In humans, antidepressants significantly increase the production of
      interleukin-10 (IL-10), a negative immunoregulatory cytokine. The aims of the
      present study were to examine the effects of desipramine, a tricyclic
      antidepressant, on the IRS in C57BL/6 mice with and without exposure to chronic
      mild stress (CMS). METHODS: We examined the effects of desipramine on the
      cytotoxic activity of natural killer (NK) cells, the proliferative responses of
      lymphocytes after stimulation with IL-1, IL-2, lipopolysaccharide (LPS),
      concanavaline-A (Con-A), phytohaemagglutinin-P (PHA), pokeweed mitogen (PWM), and
      anti-CD3 monoclonal antibodies, the production of IL-2, IL-4, IL-10 and
      interferon-gamma (IFNgamma) by T lymphocytes and the ability of B cells to
      proliferate after stimulation by lipopolysaccharide (LPS). RESULTS: Prolonged
      treatment of C57BL/6 mice subjected to CMS with desipramine increases the ability
      of T cells to produce IL-10 and the ability of B cells to proliferate after
      stimulation with LPS; and significantly decreases the cytotoxic activity of NK
      cells and the proliferative responses of lymphocytes after stimulation with Con
      A, PHA and anti-CD3 monoclonal antibodies. Repeated administration of desipramine
      to non-stressed mice increases the activity of T lymphocytes, lowers that of B
      lymphocytes, increases the production of IL-10 by T cells and has no significant
      effect on the activity of NK cells. CONCLUSION: Prolonged desipramine treatment
      of stressed and non-stressed C57BL/6 mice induces an increase in the production
      of IL-10, an anti-inflammatory cytokine.

PMID- 11246094
TI  - The influence of positive and negative mood states on risk taking, verbal
      fluency, and salivary cortisol.
AB  - BACKGROUND: significant frontal cortex dysfunction. It is hypothesised that
      performance on frontal lobe tasks may be sensitive to induced fluctuations in
      mood state in non-clinical samples. METHODS: Subjects performed one of two
      neuropsychological tasks immediately subsequent to a musical mood induction
      procedure designed to induce either elation or depression. Mood was assessed
      using self-report measures. Salivary cortisol levels were also measured in an
      attempt to objectively validate mood induction effects. The tasks used were
      verbal fluency and Damasio's Gambling Game. Two groups of subjects were
      recruited: a group with previous (subclinical) hypomanic experience (n=23) and a
      control group without previous hypomanic experience (n=23). RESULTS: The positive
      and negative mood inductions produced robust and contrasting effects on self
      reported mood, but had no significant differential effects on salivary cortisol
      levels and neuropsychological performance. LIMITATIONS: The findings are
      restricted by the absence of a neutral mood control condition. CONCLUSIONS:
      Salivary cortisol recording does not provide a simple and reliable method of
      validating psychological mood induction. Performance on frontal lobe tests
      appears to be insensitive to normal mood fluctuations, which supports the
      argument that the deficits in mood disorder patient groups may instead reflect
      core disturbances of neurobiological processes.

PMID- 11246095
TI  - International development of the Quality of Life in Depression Scale (QLDS).
AB  - BACKGROUND: The Quality of Life in Depression Scale (QLDS) employs the needs
      based model of quality of life (QoL) and was developed in the UK and The
      Netherlands as an outcome measure for clinical trials. This paper describes the
      production and psychometric assessment of nine new language versions for Canada
      (French and English), Denmark, France, Germany, Italy, Morocco, Spain and the US.
      METHODS: Three adaptation stages were employed; production of conceptually
      equivalent translations, field-test interviews and assessment of reliability and
      construct validity by survey of patients with major depression. RESULTS: Few
      problems were experienced with producing conceptually equivalent translations,
      except in Morocco. Patients in the field-test interviews found the instrument to
      have appropriate content and to be easy to complete. Internal consistency and
      test-retest reliability were excellent for all language versions and scores were
      found to relate appropriately to measures of depression severity and health
      status. LIMITATIONS: Further investigation is required of the ability of the
      measure to assess individuals at the extremes of the QoL continuum. Data
      collected with the Arabic QLDS should not be combined with those from other
      countries. CONCLUSIONS: The QLDS is the first instrument designed to assess QoL
      in depression based on a coherent model of the construct. Each language version
      has been shown to be well accepted by respondents and to have excellent
      psychometric properties. As the instrument is now available in a large number of
      languages, the QLDS is the QoL instrument of choice for inclusion in clinical
      trials of interventions for depression.

PMID- 11246096
TI  - Infant massage improves mother-infant interaction for mothers with postnatal
      depression.
AB  - BACKGROUND: Postnatal depression can have long term adverse consequences for the
      mother-infant relationship and the infant's development. Improving a mother's
      depression per se has been found to have little impact on mother-infant
      interaction. The aims of this study were to determine whether attending regular
      massage classes could reduce maternal depression and also improve the quality of
      mother-infant interaction. METHOD: Thirty-four primiparous depressed mothers,
      median 9 weeks postpartum, identified as being depressed following completion of
      the Edinburgh Postnatal Depression Scale (EPDS) at 4 weeks postpartum, were
      randomly allocated either to an infant massage class and a support group (massage
      group) or to a support group (control group). Each group attended for five weekly
      sessions. Changes in maternal depression and mother-infant interaction were
      assessed at the beginning and the end of the study by comparing EPDS scores and
      ratings of videotaped mother-infant interaction. RESULTS: The EPDS scores fell in
      both groups. Significant improvement of mother-infant interaction was seen only
      in the massage group. LIMITATION: The sample size was small and had relatively
      high dropout. It was not possible to distinguish which aspects of the infant
      massage class contributed to the benefit. CONCLUSION: This study suggests that
      learning the practice of infant massage by mothers is an effective treatment for
      facilitating mother-infant interaction in mothers with postnatal depression.

PMID- 11246097
TI  - Measuring depression in women around menopausal age: towards a validation of the
      Edinburgh Depression Scale.
AB  - BACKGROUND: The relationship between menopause and depression is still rather
      unclear. Studies using different methodology - especially those lacking a clear
      definition of depression - are hardly comparable. Since the Edinburgh Depression
      Scale (EDS) is not influenced by (menopause-related) somatic symptoms, the
      validity of the Dutch version of this instrument was investigated in a large
      community sample of menopausal women. METHODS: In 951 women, aged between 47 and
      56 years, depressive symptomatology was measured using the EDS, together with a
      syndromal diagnosis of depression using Research Diagnostic Criteria. RESULTS:
      Twenty-two percent of the subjects had scores of 12 or higher on the EDS. With
      this cut-off point, depression (major or minor) was detected with a sensitivity
      of 66%, a specificity of 89%, and a positive predictive value (PPV) of 62%. A cut
      off score of 15 or higher detected half of the women with major depression
      (sensitivity 73%, specificity 93%, PPV 53%). LIMITATIONS: Screening of depressive
      symptomatology at menopausal age in women of the community can only partly detect
      women with clinical depression. The relation between menopausal status and
      depression should preferentially be investigated using a longitudinal rather than
      a cross-sectional design. CONCLUSIONS: The EDS, which is easy to implement in
      both community and clinical settings (e.g., General Practice), might be used as
      an effective screening tool for detecting women at menopausal age who are at risk
      for depression, followed by clinical evaluation in those with high scores.

PMID- 11246098
TI  - 15-year outcome of treated bipolar disorder.
AB  - BACKGROUND: Prior reports suggested that bipolar patients in Taiwan had
      comparable long-term outcome to Western patients despite markedly lower rates of
      co-occurring substance use disorders. Thus, predictors of long-term outcome
      identified from Taiwanese bipolar samples may be less influenced by substance
      abuse. METHODS: One hundred and one patients with bipolar disorder (DSM-III-R)
      having been naturalistically treated for at least 15 years were recruited. These
      patients were annually followed for 2 years to assess overall outcome,
      psychiatric symptoms, rehospitalization, work, and social adjustment. A
      combination of medical record reviews and direct personal interviews with
      patients and family members provided the clinical data. RESULTS: Of these
      patients, 16.8% expressed a poor overall long-term outcome, even though only two
      (2.0%) patients exhibited alcohol dependence during the follow-up period.
      Multivariate regression showed that full compliance with medication was the
      strongest predictor of favorable overall long-term outcome, followed by younger
      age at onset and male sex. Younger age at onset as well as male sex, but not full
      compliance, also predicted a favorable psychosocial outcome. LIMITATIONS:
      Recruiting our sample from a clinical population with uncontrollable long-term
      treatment limits the generalizability of the findings. CONCLUSIONS: Compliance
      with pharmacotherapy is important to achieve a favorable overall long-term
      outcome of bipolar disorder. A portion of bipolar patients may have an
      unfavorable psychosocial outcome regardless of the psychopharmacological
      intervention or presence of substance abuse.

PMID- 11246099
TI  - Elevated plasma nitrate levels in depressive states.
AB  - BACKGROUND: Previous studies have shown that nitric oxide (NO) synthase
      inhibitors show preclinical antidepressant-like properties, suggesting that NO is
      involved in the pathogenesis of depression. The purpose of this study is to
      examine whether or not NO production increases in depressed patients. METHODS:
      Plasma nitrate concentrations, an index of NO production, were measured by high
      performance liquid chromatography in depressed patients (n=17) and compared with
      patients suffering anxiety (n=6) and with healthy controls (n=12). RESULTS:
      Plasma nitrate concentrations were significantly higher in depressed patients
      than in patients with an anxiety disorder (P<0.05) or in controls (P<0.01).
      LIMITATIONS: The study group was small. The source of the surplus production of
      NO in patients with major depressive episode remains unclear. CONCLUSIONS: These
      results suggest that NO production is increased in depression.

PMID- 11246100
TI  - Anti-depressant prescribing patterns for prison inmates with depressive
      disorders.
AB  - BACKGROUND: Although prison inmates are reported to exhibit elevated rates of
      depressive disorders, little is known about anti-depressant prescribing patterns
      in correctional institutions. METHODS: The study population consisted of 5305
      Texas Department of Criminal Justice (TDCJ) inmates who were diagnosed with one
      of three depressive disorders: major depression, dysthymia, and bipolar disorder
      (excluding those with manic episodes only). Information on medical conditions,
      sociodemographic factors, and pharmacotherapy was obtained from an institution
      wide medical information system. RESULTS: In 1998, 78.2% of all inmates diagnosed
      with depressive disorders were treated with antidepressant medication. Of these,
      47.3% were treated exclusively with tricyclic anti-depressants (TCA); 30.9% were
      treated with selective serotonin re-uptake inhibitors (SSRI); and 21.8% were not
      treated with any form of anti-depressant medication. Prescribing patterns varied
      substantially according to a number of sociodemographic factors under study.
      LIMITATIONS: Because the present study relied on retrospective, clinical data,
      the investigators had limited ability to assess: specific symptomatology for each
      diagnosed depressive condition under study; socio-economic status, pre
      incarceration access to health care; and the overall reliability and validity of
      the data. CONCLUSION: The proportion of prison inmates with depressive disorders
      who receive appropriate medication management is substantially higher than that
      reported among similarly diagnosed nonincarcerated samples. It will be important,
      however, for future investigators to examine the sources of sociodemographic
      variation in treatment patterns found in the present study.

PMID- 11246101
TI  - Screening for postnatal depression: are specific instruments mandatory?
AB  - BACKGROUND: Few studies have examined the utility of rating scales developed in
      non-puerperal context in detecting postnatal depression. This study evaluated the
      utility of the General Health Questionnaire (GHQ) and the Beck Depression
      Inventory (BDI) in screening for depression among recently delivered women in
      Hong Kong. METHODS: A prospective cohort of 145 Chinese women completed the GHQ,
      BDI and Edinburgh Postnatal Depression Scale (EPDS) 6 weeks after delivery. They
      were then assessed using the non-patient version of the Structured Clinical
      Interview for DSM-III-R (SCID-NP) to establish psychiatric diagnosis, against
      which the criterion validity of the GHQ and BDI was evaluated against this
      clinical diagnosis. The psychometric performance of the GHQ, BDI and EPDS in
      detecting postnatal depression was assessed using the receiver operating
      characteristic (ROC) curves. RESULTS: Both Chinese GHQ and BDI had satisfactory
      sensitivity and positive predictive value in detecting postnatal depression.
      Their receiver operating characteristic (ROC) curves were comparable to that of
      the EPDS. LIMITATION: The study was conducted in Chinese women using translated
      version of the rating scales. CONCLUSIONS: The GHQ and BDI are useful for
      detecting postnatal depression among recently delivered Chinese women. The
      results of this study suggest that rating scales developed in non-puerperal
      context may also be applicable for postnatal depression.

PMID- 11246102
TI  - Prevalence of premenstrual dysphoric disorder in female patients with seasonal
      affective disorder.
AB  - BACKGROUND: Both seasonal affective disorder/winter type (SAD) and premenstrual
      dysphoric disorder (PMDD) are cyclical disorders characterized by so-called
      atypical depressive symptoms. In the present study we compared the point
      prevalence rates of PMDD between a sample of premenopausal female patients
      suffering from SAD and healthy female controls. METHODS: Forty-six female
      patients with SAD and 46 healthy controls were included in our study. All
      subjects underwent a semistructured clinical interview according to DSM IV
      criteria and completed the Seasonal Pattern Assessment Questionnaire. PMDD was
      diagnosed in a self-rating interview for PMDD according to DSM IV criteria. To
      verify the diagnosis of PMDD, all patients were followed up in stable summer
      remission using daily self-rating scales for two full menstrual cycles. RESULTS:
      Patients with SAD fulfilled significantly more often the diagnostic criteria for
      PMDD than female healthy controls (46% vs. 2%, respectively; chi-square:
      P<0.001). CONCLUSIONS: These results provide preliminary evidence for a high
      point prevalence rate of PMDD in premenopausal females with SAD. CLINICAL
      IMPLICATIONS: It would be worthwhile to investigate whether an additional
      diagnosis of PMDD has an impact on the clinical outcome and the response to
      bright light therapy in female patients with SAD.

PMID- 11246103
TI  - Adjunctive gabapentin in treatment-resistant depression: a retrospective chart
      review.
AB  - BACKGROUND: Previous studies in predominantly bipolar patients have suggested
      that gabapentin may be useful in treating mood disorders. This report describes
      its efficacy and tolerability as an adjunctive agent in treatment-resistant
      depression. METHODS: A chart review was conducted on 27 outpatients presenting
      with a depressive disorder in whom gabapentin was added to ongoing treatment with
      a conventional antidepressant to which patients had not responded after at least
      6 weeks. The majority of patients had either prominent anxiety or a history of
      soft bipolar features, but patients with bipolar I disorder were excluded.
      Clinical state and adverse effects were assessed retrospectively at each visit.
      RESULTS: Mean gabapentin trial duration was 15.2+/-7.8 weeks, with a mean final
      dose of 904+/-445 mg/day (range, 300-1800 mg/day). Clinician-rated measures of
      clinical state improved significantly from baseline to endpoint. Overall, 37.0%
      (n=10) of patients were responders at endpoint; another 18.5% (n=5) manifested a
      transient response not sustained to endpoint. Gabapentin was well tolerated; the
      most common adverse effects were fatigue, sedation, dizziness, and
      gastrointestinal symptoms. LIMITATIONS: Treatment was uncontrolled and efficacy
      assessments were retrospective. CONCLUSION: These findings suggest that
      gabapentin may be of adjunctive benefit in the management of treatment-resistant
      depression.

PMID- 11246104
TI  - Primary and secondary depersonalisation disorder: a psychometric study.
AB  - INTRODUCTION: Depersonalisation may be part of a symptom-complex, a primary or a
      secondary disorder. Optimal methods of measurement and diagnosis have not been
      established. METHODS: We assessed 42 patients with primary or secondary
      depersonalisation, plus psychiatric and non-psychiatric controls using a variety
      of self-report questionnaire scales including the Beck depression and anxiety
      Inventories, and one developed by the authors (the Fewtrell Depersonalisation
      Scale (FDS)). The correlations between the scales and measures of anxiety and
      depression were calculated, as were sensitivity and specificity against an
      operational case definition. RESULTS: All the scales were highly correlated. All
      could distinguish depersonalisation cases from the rest but none could
      distinguish between primary and secondary depersonalisation disorder. Anxiety and
      especially depression were correlated with depersonalisation symptoms. The FDS
      had high sensitivity (85.7%) and specificity (92.3%) which compared favourably
      with other instruments. Patients with both derealisation and depersonalisation
      scored the highest on the FDS. DISCUSSION: Depersonalisation disorder comprises a
      measurable cluster of symptoms which may be quantified with the help of self
      report scales. Primary and secondary forms overlap, with depressed mood a
      frequent feature.

PMID- 11246106
TI  - Applying concepts, deductive reasoning and integrative physiology at the bedside.

PMID- 11246107
TI  - McCance paper revisited: 65 years gone by.

PMID- 11246108
TI  - Medical problems in mineral metabolism. 1936.

PMID- 11246109
TI  - The approach to a patient with acute polyuria and hypernatremia: a need for the
      physiology of McCance at the bedside.
AB  - We present a case to illustrate the importance of emphasizing elementary
      physiology to deduce the basis for the acute onset of polyuria and hypernatremia.
      An imaginary consultation with Professor McCance is utilized to illustrate how a
      clinician-physiologist would have explained why these abnormalities developed and
      how they should have been treated. His approach began with a consideration of the
      most impressive abnormality. His analysis relied heavily on deductions and the
      anticipation of the expected responses to a stimulus in quantitative terms. The
      goals of therapy became evident after he performed mass balance calculations.
      Professor McCance would not understand why modern clinicians abandoned this form
      of analysis.

PMID- 11246110
TI  - Intravenous fluid therapy taken into theoretical and practical consideration:
      physiology revisited.

PMID- 11246111
TI  - Hyponatremia in intracranial disorders.
AB  - Hyponatremia is a common electrolyte disturbance following intracranial
      disorders. Hyponatremia is of clinical significance as a rapidly decreasing serum
      sodium concentration as well as rapid correction of chronic hyponatremia may lead
      to neurological symptoms. Especially two syndromes leading to hyponatremia in
      intracranial disorders need to be distinguished, as they resemble each other in
      many, but not all ways. These are the syndrome of inappropriate ADH secretion
      (SIADH) and the cerebral salt wasting syndrome (CSW). The syndrome of
      inappropriate ADH secretion is characterized by water retention, caused by
      inappropriate release of ADH, leading to dilutional hyponatremia. The cerebral
      salt wasting syndrome on the other hand, represents primary natriuresis, leading
      to hypovolemia and sodium deficit. SIADH should be treated by fluid restriction,
      whereas the treatment of CSW consists of sodium and water administration.
      However, in the literature there is abundant evidence that hyponatremia in
      intracranial diseases is mostly caused by CSW. Therefore, treatment with fluid
      and salt supplementation seems indicated in patients with intracranial disorders
      who develop hyponatremia and natriuresis.

PMID- 11246112
TI  - Lactic acidosis: pathophysiology, diagnosis and treatment.
AB  - Lactic acidosis is common in severely ill patients. We describe four patients
      with a lactic acidosis combined with other acid-base disturbances. In daily
      practice it is important to consider these combined disturbances since there is
      no specific treatment in lactic acidosis. Treating the underlying causes of the
      acid-base disturbances is the only warranted intervention. However, lactic
      acidosis is still associated with high mortality.

PMID- 11246113
TI  - Lithium-induced nephrogenic diabetes insipidus.
AB  - Two patients with severe lithium-induced nephrogenic diabetes insipidus are
      described. Although it is known lithium can cause diabetes insipidus, one should
      be especially alert in psychiatric patients, as the main defence mechanisms
      thirst and drinking behaviour may not function adequately in these patients. The
      major form of therapy in both patients consisted of drinking, a thiazide
      diuretic, as well as a protein and sodium restricted diet.

PMID- 11246114
TI  - Hyponatremia due to hypothyroidism: a pure renal mechanism.
AB  - Hyponatremia is a common disorder. When hyponatremia is the result of
      hypothyroidism it can be successfully treated with thyroid hormone substitution.
      We followed cumulative sodium- and fluid balances of a patient with hyponatremia,
      resulting from hypothyroidism. We concluded that hyponatremia in hypothyroidism
      is due to a pure renal mechanism, and cannot be ascribed to inappropriate
      secretion of antidiuretic hormone.

PMID- 11246115
TI  - Hypernatremia in a non insulin dependent (type 2) diabetic patient with central
      diabetes insipidus.
AB  - We describe a patient with central diabetes insipidus who presented with
      hyperosmolar, non-ketotic hyperglycaemia. The role in this case of reduced thirst
      sensation with decreased water intake and abnormal AVP production illustrates the
      importance of these protective mechanisms in normal physiology regarding
      maintenance of normal plasma osmolality. Despite the complex pathophysiology in
      this patient, fluid resuscitation aimed at normalisation of the water deficit
      resulted in full recovery.

PMID- 11246116
TI  - Sixty-eight-year-old patient with hypokalemia.
AB  - A 68-year-old patient with severe hypokalemia and metabolic alkalosis is
      described. Six years before admission he had been treated for a small cell
      bronchial carcinoma. We discuss the diagnostic approach of hypokalemia and the
      way in which we reached the diagnosis. The patient suffered from metastatic small
      cell carcinoma with a very high plasma adrenocorticotropic hormone concentration,
      possibly due to production of corticotropin-releasing hormone by the malignancy.

PMID- 11246117
TI  - Laudatio in honour of Professor Hanspeter Witschi, the retired Editor for the
      Americas and Japan.

PMID- 11246118
TI  - Gel microdrop flow cytometry assay for low-dose studies of chemical and radiation
      cytotoxicity.
AB  - Low-level cytotoxicity may affect low-dose dose-response relations for cancer and
      other endpoints. Conventional colony-forming assays are rarely sensitive enough
      to examine small changes in cell survival and growth. Automated image-analysis
      techniques are limited to ca. 10(4) cells/plate. An alternative method involves
      encapsulation of single proliferating cells into ca. 35-75-microm-diameter
      agarose gel microdrops (GMDs) that are randomly grouped, differential exposure of
      these groups, culture at 37 degrees C for 3-5 days, and finally GMD analysis by
      flow cytometry (FC) to determine the ratio of GMDs containing multiple versus
      single cells as a measure of clonogenic survival. This GMD/FC assay was used to
      examine low-dose cell killing induced by a cooked-meat mutagen/rodent-carcinogen
      (MeIQx) in DNA-repair-deficient/metabolically-sensitive CHO cells. Results of
      conventional colony-forming assays using up to 30 replicate plates indicate a
      shouldered, threshold-like dose-response; in contrast, those obtained using the
      GMD/FC assay suggest "hypersensitivity"-like nonlinearity in dose-response. The
      GMD/FC assay was also applied to human A549 lung cells after GMD-encapsulation
      and gamma radiation followed by culture for a total of 4 days, to examine
      survival after exposure to > or =100 cGy delivered at a relatively low dose rate
      (0.18 cGy/min). Dose-response for clonogenic growth was again observed to be
      reduced with apparent nonlinear suggesting hypersensitivity between 0 and 50 cGy,
      insofar as doses of 5 and 10 cGy appear to be ca. fivefold more effective per
      unit dose than the 50- or 100-cGy doses used. The GMD/FC assay may thus reveal
      low-dose dose-response relations for chemical and radiation effects on cell
      proliferation/killing with implications for low-dose risk assessment.

PMID- 11246119
TI  - Cytosolic xanthine oxidoreductase mediated bioactivation of ethanol to
      acetaldehyde and free radicals in rat breast tissue. Its potential role in
      alcohol-promoted mammary cancer.
AB  - Epidemiological evidence links alcohol intake with increased risk in breast
      cancer. Not all the characteristics of the correlation can be explained in terms
      of changes in hormonal factors. In this work, we explore the possibility that
      alcohol were activated to acetaldehyde and free radicals in situ by xanthine
      dehydrogenase (XDh) and xanthine oxidase (XO) and/or aldehyde oxidase (AO).
      Incubation of cytosolic fraction with xanthine oxidoreductase (XDh+XO) (XOR)
      cosubstrates (e.g. NAD+, hypoxanthine, xanthine, caffeine, theobromine,
      theophylline or 1,7-dimethylxanthine) significantly enhanced the
      biotransformation of ethanol to acetaldehyde. The process was inhibited by
      allopurinol and not by pyrazole or benzoate or desferrioxamine and was not
      accompanied by detectable formation of 1HEt. However, hydroxylated aromatic
      derivatives of PBN were detected, suggesting either that hydroxyl free radicals
      might be formed or that XOR might catalyze aromatic hydroxylation of PBN. No
      bioactivation of ethanol to acetaldehyde was detectable when a cosubstrate of AO
      such as N-methylnicotinamide was included in cytosolic incubation mixtures.
      Results suggest that bioactivation of ethanol in situ to a carcinogen, such as
      acetaldehyde, and potentially to free radicals, might be involved in alcohol
      breast cancer induction. This might be the case, particularly also in cases of a
      high consumption of purine-rich food (e.g. meat) or beverages or soft drinks
      containing caffeine.

PMID- 11246120
TI  - Intracellular signal transduction pathways as targets for neurotoxicants.
AB  - The multiple cascades of signal transduction pathways that lead from receptors on
      the cell membrane to the nucleus, thus translating extracellular signals into
      changes in gene expression, may represent important targets for neurotoxic
      compounds. Among the biochemical steps and pathways that have been investigated
      are the metabolism of cyclic nucleotides, the formation of nitric oxide, the
      metabolism of membrane phospholipids, the activation of a multitude of protein
      kinases and the induction of transcription factors. This brief review will focus
      on the interactions of three known neurotoxicants, lead, ethanol and
      polychlorinated biphenyls, with signal transduction pathways, particularly the
      family of protein kinase C isozymes, and discusses how such effects may be
      involved in their neurotoxicity.

PMID- 11246121
TI  - Pesticide use in developing countries.
AB  - Chemical pesticides have been a boon to equatorial, developing nations in their
      efforts to eradicate insect-borne, endemic diseases, to produce adequate food and
      to protect forests, plantations and fibre (wood, cotton, clothing, etc.).
      Controversy exists over the global dependence on such agents, given their
      excessive use/misuse, their volatility, long-distance transport and eventual
      environmental contamination in colder climates. Many developing countries are in
      transitional phases with migration of the agricultural workforce to urban centres
      in search of better-paying jobs, leaving fewer people responsible for raising
      traditional foods for themselves and for the new, industrialized workforce.
      Capable of growing two or three crops per year, these same countries are becoming
      "breadbaskets" for the world, exporting nontraditional agricultural produce to
      regions having colder climates and shorter growing seasons, thereby earning much
      needed international trade credits. To attain these goals, there has been
      increased reliance on chemical pesticides. Many older, nonpatented, more toxic,
      environmentally persistent and inexpensive chemicals are used extensively in
      developing nations, creating serious acute health problems and local and global
      environmental contamination. There is growing public concern in these countries
      that no one is aware of the extent of pesticide residue contamination on local,
      fresh produce purchased daily or of potential, long-term, adverse health effects
      on consumers. Few developing nations have a clearly expressed "philosophy"
      concerning pesticides. There is a lack of rigorous legislation and regulations to
      control pesticides as well as training programs for personnel to inspect and
      monitor use and to initiate training programs for pesticide consumers.

PMID- 11246122
TI  - Regulation of mucous differentiation and mucin gene expression in the
      tracheobronchial epithelium.
AB  - The goal of our studies is to elucidate mechanisms that control and modulate
      mucous differentiation and mucin gene expression in the conducting airways. We
      used cultures of normal human tracheobronchial epithelial (NHTBE) cells that were
      shown to secrete two major airway mucins, namely MUC5AC and MUC5B as well as
      several other secretory products. Mucous differentiation and expression of MUC2,
      MUC5AC, MUC5B and MUC7, but not MUCi, MUC4, and MUC8 mucin genes, were shown to
      be retinoic acid- (RA) or retinol-dependent. We found that RA control of mucin
      genes was mediated by the retinoid acid receptors RAR alpha and, to a lesser
      extent, by RAR gamma. Our studies also showed that other important bioregulators
      such as thyroid hormone (T3) and epidermal growth factor (EGF) modulate basal
      expression of mucin genes, interacting with RA in a concentration-dependent
      manner. T3, which binds to thyroid receptors (TRs) belonging to the same
      superfamily of steroid hormone nuclear receptors as the RARs, inhibits mucin gene
      expression, particularly MUC5AC. One possible mechanism of this T3 effect is
      downregulation of RAR proteins, which are critical for mucin gene expression.
      However, we also found that T3 inhibits MUC5AC transcription.EGF, which had
      previously been shown to stimulate mucin expression and mucin secretion in
      cultured rat tracheal epithelial (RTE) cells, inhibited mucin secretion in human
      bronchial epithelial cell cultures. This effect was EGF concentration- and time
      dependent and was progressively abolished by increasing the RA concentration.
      Subsequent studies suggested that the inhibitory effects of high concentrations
      of EGF may result from selective reduction of MUC5AC expression. These studies
      thus point to potentially important species differences in the mechanisms
      regulating mucous production, and they also confirm previous findings indicating
      differential regulation of MUC5AC and MUC5B gene expression.

PMID- 11246123
TI  - Investigation of the role of the 2',3'-epoxidation pathway in the bioactivation
      and genotoxicity of dietary allylbenzene analogs.
AB  - The genotoxic potential of naturally occurring allylbenzene analogs, including
      safrole, eugenol, estragole, and others, has been examined in many studies over
      the past 30 years. It has been established that these compounds are subject to
      biotransformation in the liver, which can lead to the formation of reactive
      electrophilic intermediates. The major route of bioactivation is via
      hydroxylation of the 1' carbon atom of the allylic side chain. We have
      synthesized 2',3'- (allylic) epoxide derivatives of allylbenzene, estragole
      eugenol and safrole, and have used them to characterize the genotoxic potential
      of epoxidation at the allylic double bond for allylbenzene and its naturally
      occurring analogs. In order to assert that this pathway has the potential for
      genotoxicity, it is necessary to demonstrate (1) that epoxide metabolites of
      these compounds are capable of forming covalent adducts with DNA bases; and (2)
      that these epoxide metabolites are actually formed in vivo. We have demonstrated
      that allylic epoxides derived from allylbenzene and estragole are capable of
      forming covalent adducts with all four deoxyribonucleotides in vitro and, in the
      case of deoxyguanosine, form at least four different adducts. We also deduce,
      from evidence obtained using the isolated perfused rat liver, that formation of
      potentially genotoxic 2',3' epoxide metabolites occurs readily in vivo, but that
      these metabolites are rapidly further metabolized to less toxic dihydrodiol or
      glutathione conjugates. We conclude that 2',3' epoxide metabolites of
      allylbenzene analogs are formed in vivo and that these epoxides are sufficiently
      reactive to facilely form covalent bonds with DNA bases. Epoxide formation at the
      allylic double bond represents, therefore, a potentially genotoxic bioactivation
      pathway for allylbenzene analogs. However, comparison of the relative kinetics of
      epoxide metabolism and epoxide formation suggests that a wide margin of
      protection from DNA covalent adduct formation exists in the rat liver, thus
      preventing genotoxicity resulting from this pathway to any significant degree. In
      this regard, we have also observed that the general rate of epoxide hydrolysis is
      much greater in human liver than in rat liver. We therefore suggest that while
      the epoxidation pathway poses a potential genotoxic threat to humans, no actual
      genotoxicity occurs as a result of this metabolic pathway.

PMID- 11246124
TI  - Global toxicology and risk analysis: roles of the Internet and World Wide Web.
AB  - There are many challenges and opportunities in being a global and/or "local"
      toxicologist, risk assessor, or risk manager. These include the information
      gathering approaches used to address human hazard identification, exposure
      assessment, risk characterization, risk management, risk perceptions, and needs
      for risk communication. Finding the best ways to keep current with the literature
      and other information associated with the many aspects of toxicology and risk
      analysis is another challenge and opportunity, as are access to good sources of
      training and staying aware of the applicable regulations in various countries and
      regions. Fortunately, a greatly increasing number of people throughout the world
      will have access to the Internet and World Wide Web; these systems provide 24 h a
      day access to numerous valuable sources of information and opportunities for
      training and information sharing.

PMID- 11246125
TI  - Cadmium adaptation in the lung - a double-edged sword?
AB  - This review article discusses the major cellular and molecular responses
      characterizing pulmonary adaptation to cadmium (Cd) that may ultimately
      contribute to Cd carcinogenesis. Hallmarks of Cd adaptation include hyperplasia
      and hypertrophy of type II alveolar epithelial stem cells, an inflammatory
      response involving polymorphonuclear leukocytes, and the increased gene and
      protein expression of several resistance factors. The most prominent biochemical
      change is associated with Cd-induced up-regulation of metallothionein, a cysteine
      rich, metal-binding protein that sequesters Cd and also possesses considerable
      free radical scavenging ability. Increased levels of glutathione (GSH) and
      induction of enzymes involved with both the synthesis of GSH (gamma
      glutamylcysteine synthetase regulatory and catalytic subunits) and its metabolism
      (GSH S-transferases) also constitute important components of the pulmonary
      adaptive response. Enhancement of several important cellular defense systems in
      response to Cd exposure may, at first, appear to be beneficial. However, recent
      evidence suggests that the Cd-adaptive phenotype could have deleterious
      consequences and may represent a double-edged sword. It has been discovered that
      Cd-adapted alveolar epithelial cells have a reduced ability to repair DNA damage
      due, in part, to the inhibition of two base excision repair enzymes (8-oxoguanine
      DNA glycosylase and endonuclease III). Cells with genetic aberrations resulting
      from unrepaired DNA lesions would normally be removed from the lung by apoptosis.
      However, another study has demonstrated that apoptotic cell death, following an
      oxidant challenge, is significantly attenuated in Cd-adapted cells compared to
      non-adapted counterparts. Suppressed apoptosis could leave pre-neoplastic or
      neoplastic cells alive, favor their clonal expansion, and ultimately promote
      tumor development. The presence of superior antioxidant defenses would also be
      expected to increase the resistance of these tumors to chemotherapeutic agents.

PMID- 11246126
TI  - Species and organ specificity of fumonisin-induced endothelial alterations:
      potential role in porcine pulmonary edema.
AB  - Fumonisins, mycotoxins that commonly contaminate corn, induce cardiovascular
      toxicity and pulmonary edema in pigs, leukoencephalomalacia in horses, and
      nephropathy in rats, rabbits, and lambs. The mechanisms of these species-specific
      target organ toxicoses are poorly understood. We have previously reported
      perinuclear accumulation of membranous material in pulmonary capillary
      endothelial cells of pigs fed fumonisin-containing culture material. We
      hypothesized that these endothelial accumulations may be important in the
      pathogenesis of fumonisin-induced pulmonary edema and target organ toxicity in
      other species. Both target and non-target tissues from fumonisin-exposed pigs,
      sheep, rabbits, and rats were examined ultrastructurally. Specifically, lung,
      liver, heart and kidney were examined. In agreement with our previous work
      (Gumprecht, L.A., Beasley, V.R., Weigel, R.M., Parker, H.M., Tumbleson, M.E.,
      Bacon, C.W., Meredith, F.I., Haschek, W.M., 1998. Development of fumonisin
      induced hepatotoxicity and pulmonary edema in orally dosed swine: morphological
      and biochemical parameters. Tox. Pathol. 26, 777-788), endothelial alterations
      were present in the pulmonary capillary endothelial cells of pigs fed fumonisin
      containing culture material, but at doses that did not induce pulmonary edema, as
      well as in pigs injected intravenously with purified fumonisin B(1). These
      alterations were present only in the pulmonary capillary endothelium of pigs and
      not in other species. In addition, these endothelial alterations were not present
      in any other organ of pigs or other species examined. Thus, these endothelial
      alterations are induced by fumonisin B(1), but only in pulmonary capillary
      endothelium and only in pigs. Although evidence that these alterations play a
      role in fumonisin-induced pulmonary edema is limited, other endothelial functions
      may be affected by fumonisin treatment.

PMID- 11246127
TI  - Urinary butadiene diepoxide: a potential biomarker of blood diepoxide.
AB  - The carcinogenicity of 1,3-butadiene (BD) varies greatly in the rodent species in
      which 2-year bioassay studies were completed. This raises the question of whether
      the risk of BD exposure in humans is more like that of the sensitive species, the
      mouse, or more like that of the resistant species, the rat. Numerous studies have
      indicated that one reason for the species differences in response to BD is that
      the blood and tissues of BD-exposed mice contain high levels of both the mono-
      and the diepoxide metabolite, while the tissue and blood of exposed rats contain
      very little of the diepoxide. The diepoxide is far more mutagenic than the
      monoepoxide, and so it is reasonable that the diepoxide plays a major role in
      tumor induction in the mouse. If the diepoxide is the primary carcinogen, the
      presence of the diepoxide in the blood of exposed individuals should be an
      indicator of risk from BD exposure. In this study, we report that the diepoxide
      is sufficiently stable to be excreted into the urine of exposed rodents and that
      the urinary levels of the diepoxide reflect the relative levels of the compound
      in the blood of the two species. The conclusion is that urinary diepoxide should
      be investigated as a potential biomarker of the formation of the diepoxide in
      humans exposed to BD.

PMID- 11246128
TI  - Confounding factors in toxicity testing.
AB  - The necessity for understanding normal human functions and the mechanisms which
      underlie dysfunction in these processes is essential in the promotion of a
      healthier lifestyle. To achieve this goal utilization of a suitable animal model
      is necessary in order to develop new pharmaceutical agents to alleviate diseases
      or chemicals to enhance the quality of life. It is incumbent upon investigators
      to choose a species in which pharmacokinetic principles are established and it is
      important that these phenomena resemble those of the humans. The choice of rats
      has specific advantages in that these rodents possess similar pharmacodynamic
      parameters to humans. Other advantages include availability, low cost, ease of
      breeding, and an extensive literature data-base to enable comparisons to present
      findings. However, in the interpretation of data from animals to humans, there
      are factors which need to be recognized as playing important roles in chemical
      induced outcomes. The confounding factors include strain, supplier, age, gender,
      hormonal status and dietary intake. The aim of this article is to demonstrate
      that there are differences in the responsiveness of rat stock/strains to
      chemicals and that lack of consideration of confounding factors yields
      inappropriate conclusions regarding risk assessment for humans.

PMID- 11246130
TI  - A perspective on the progression of immunotoxicology.
AB  - Immunotoxicology originated in the early 1970s, when scientists began
      investigating chemicals. During the 1970s and early 1980s, a few investigators
      determined that chemicals were immunotoxic, developed and/or refined
      immunoassays, and began to characterize immunotoxic responses. In the 1980s, many
      new investigators entered the field, graduates were being trained as
      immunotoxicologists, the immune system was identified as a primary target organ,
      mechanisms of action studies proliferated, a comprehensive immunotoxicological
      panel was validated, the discipline gained universal credibility, and human
      studies emerged. The 1990s were ushered in with the concept of biological markers
      in immunotoxicology, a better understanding of "immune function", inclusion of
      immunotoxicology in risk assessment analysis, and a focus on molecular
      immunology. Future investigations will continue to improve and expand this
      foundation, pursue the relationship of immunotoxic chemicals and adverse health
      effects in humans, utilize genetically altered rodent models, and use gene
      expression technology to better understand the pathogenesis of
      immunotoxicological processes. Immunotoxicology has not only matured since its
      inception nearly 30 yr ago, but has become a prominent and respected discipline
      with global recognition; one that has made significant contributions to the
      advancement of the biomedical sciences.

PMID- 11246131
TI  - Role of macrophages and inflammatory mediators in chemically induced toxicity.
AB  - Macrophages are critical cellular effectors of nonspecific host defense. They are
      also potent secretory cells releasing an array of mediators including
      proinflammatory and cytotoxic cytokines and growth factors, bioactive lipids,
      hydrolytic enzymes and reactive oxygen and nitrogen intermediates, each of which
      has been implicated in tissue injury. The research in our laboratories has
      focused on analyzing the role of macrophages in chemically induced injury in the
      lung and the liver. In both these tissues, a localized accumulation of
      macrophages is observed following toxicant exposure. This is directly correlated
      with the generation of cytotoxic inflammatory mediators at these sites. Moreover,
      when macrophage functioning is blocked, pulmonary and hepatic injury induced by
      toxicants such as ozone or acetaminophen is prevented. These findings provide
      direct support for our hypothesis that macrophages contribute to tissue injury.
      Approaches using pharmacologic inhibitors and transgenic animals are currently
      being used to evaluate the specific macrophage-derived products involved in the
      pathogenic process. Our results suggest that the extent to which a particular
      mediator contributes to injury depends on the nature of the toxicant, the target
      tissue, and quantities of the mediator produced.

PMID- 11246129
TI  - Association between bcl-x(L) and 5-lipoxygenase activating protein (FLAP) levels
      in IL-3-dependent FL5.12 cells.
AB  - The expression of 5-lipoxygenase activating protein (FLAP) in murine
      hematopoietic FL5.12 cells that are transfected to overexpress bcl-x(L) is less
      than in control cells. In addition, the withdrawal of IL-3 from the bcl-x(L)
      overexpressing cells, but not control cells, leads to the rapid loss of FLAP even
      though these cells, in contrast to control cells, do not undergo apoptosis (Datta
      et al., J. Biol. Chem. 273, 28163-28169 [1998]). The mechanism(s) underlying
      these observations is not known. Basal FLAP mRNA levels were actually 2.8-fold
      higher in bcl-x(L) than control cells indicating that this difference does not
      have a transcription basis. In addition, an examination of FLAP mRNA levels in
      response to withdrawal of IL-3 revealed a 2-3-fold increase after 4 and 8 h
      relative to time-matched samples in both control and bcl-x(L) overexpressing
      cells. This further indicates that the decrease in FLAP levels in bcl-x(L)
      overexpressing cells is not related to transcription and suggests an attempt at
      compensation perhaps in response to increased FLAP degradation/turnover. A
      proteolytic mechanism was explored by examining the effect of the general caspase
      inhibitor Boc-D-FMK, and the non-caspase protease inhibitors phenylmethylsulfonyl
      fluoride (PMSF), pepstatin and leupeptin, on the loss of FLAP in bcl-x(L)
      overexpressing cells subsequent to IL-3 withdrawal. All inhibitors provided some
      protection from the loss of FLAP, with PMSF being the most effective, actually
      increasing FLAP levels above those seen in untreated cells. Given the absence of
      apoptosis in bcl-x(L) cells, it appears that protease activation is an effect
      that can accompany a variety of cellular perturbations. The functional
      consequences of a loss of FLAP in growth-factor deprived cells overexpressing bcl
      x(L) is not known. However, these data continue to suggest some link between bcl
      x(L) and FLAP.

PMID- 11246132
TI  - Inhibition of normal human lung fibroblast growth by beryllium.
AB  - Inhalation of particulate beryllium (Be) and its compounds causes chronic Be
      disease (CBD) in a relatively small subset ( approximately 1-6%) of exposed
      individuals. Hallmarks of this pulmonary disease include increases in several
      cell types, including lung fibroblasts, that contribute to the fibrotic component
      of the disorder. In this regard, enhancements in cell proliferation appear to
      play a fundamental role in CBD development and progression. Paradoxically,
      however, some existing evidence suggests that Be actually has antiproliferative
      effects. In order to gain further information about the effects of Be on cell
      growth, we: (1) assessed cell proliferation and cell cycle effects of low
      concentrations of Be in normal human diploid fibroblasts, and (2) investigated
      the molecular pathway(s) by which the cell cycle disturbing effects of Be may be
      mediated. Treatment of human lung and skin fibroblasts with Be added in the
      soluble form of BeSO(4) (0.1-100 microM) caused inhibitions of their growth in
      culture in a concentration-dependent manner. Such growth inhibition was found to
      persist, even after cells were further cultured in Be(2+)-free medium. Flow
      cytometric analyses of cellular DNA labeled with the DNA-binding fluorochrome
      DAPI revealed that Be causes a G(0)-G(1)/pre-S phase arrest. Western blot
      analyses indicated that the Be-induced G(0)-G(1)/pre-S phase arrest involves
      elevations in TP53 (p53) and the cyclin-dependent kinase inhibitor CDKN1A
      (p21(Waf-1,Cip1)). That Be at low concentrations inhibits the growth of normal
      human fibroblasts suggests the possibility of the existence of abnormal cell
      cycle inhibitory responses to Be in individuals who are sensitive to the metal
      and ultimately develop CBD.

PMID- 11246133
TI  - Two-dimensional gel electrophoresis: a powerful method to elucidate cellular
      responses to toxic compounds.
AB  - Humans are exposed to a variety of environmental toxicants and combinations
      thereof, and a large number of interacting factors contribute to an individual's
      risk for disease. Therefore, new strategies in toxicological research are needed
      for efficient screening of environmental hazards on complex living systems. The
      rapidly expanding field of proteomics relies heavily upon the use of two
      dimensional gel electrophoresis (2-DE) of protein samples. 2-DE is a key
      separation technique in proteome analysis due to its advantage of simultaneous
      separation of thousands of proteins at a time, excellent reproducibility, and
      ability to exhibit post-translational modifications. Therefore, 2-D proteome
      analysis is becoming a popular method of choice to detect differentially
      expressed proteins between proteome profiles after exposure to toxicants. The
      goal of this study was to examine the response of pancreas carcinoma cells to
      increasing concentrations of the cytotoxic agent daunorubicin (DRC). The
      proteomic investigation revealed a number of proteins that were up-regulated by
      DRC treatment, some in a dose-dependent manner. However, these changes were not
      seen by reverse transcriptase-polymerase chain reaction. The determination of
      proteome changes following exposure to xenobiotics will aid our understanding of
      the mechanisms of their toxicity as well as providing the possibility for the
      establishment of biomarkers that can be used in risk assessment as well as for
      the identification of individual susceptibility factors.

PMID- 11246134
TI  - Effects of heptachlor epoxide on components of various signal transduction
      pathways important in tumor promotion in mouse hepatoma cells. Determination of
      the most sensitive tumor promoter related effect induced by heptachlor epoxide.
AB  - The effects of the organochlorine (OC) liver tumor promoter heptachlor epoxide
      (HE; 0, 0.1, 1, 10, and 50 microM) on several cellular tumor promoter-sensitive
      parameters were studied in mouse 1c1c7 hepatoma cells in an effort to identify
      the most sensitive biomarker for OC promoter exposure and the critical pathway
      and target of OC promoters. The levels of Ca2+ in the endoplasmic reticulum (ER)
      store, connexin43 (Cx43), PLCgamma(1), nPKCvarepsilon, and AP-1 DNA binding in
      nucleus were studied to screen for effects induced by submicromolar HE levels.
      While all the parameters tested elicited effects, particulate PLCgamma(1) and AP
      1 DNA binding were found to be the most sensitive parameters affected by HE on
      both dose and temporal bases. Their levels were increased with 10- to 100-fold
      lower HE concentrations than were required to affect nPKCvarepsilon or Cx43.
      Further, with the lower HE dosages, particulate PLCgamma(1) and nuclear AP-1 were
      positively modulated by HE after 1 h versus 3 or 72 h for nPKCvarepsilon and
      Cx43. Ca2+ store depletion was probably the third most sensitive parameter, after
      AP-1 and PLCgamma(1). These results suggest the tyrosine kinase growth factor
      receptor pathway is the probable critical pathway for HE-induce tumor promotion
      with the critical target most likely being upstream of PLCgamma(1) and AP-1. This
      work also demonstates that upon exposure to a tumor promoter such as HE, many
      hepatocellular effects or changes result, suggesting that a cellular-program
      shift occurs similar to that described by the resistant hepatocyte model after
      exposure to a carcinogen or enzyme inducer.

PMID- 11246135
TI  - Reanalysis with optimized power of red blood cell acetylcholinesterase activity
      from a 1-year dietary treatment of dogs to chlorpyrifos.
AB  - A no-observed-effect level (NOEL) of 0.1 mg/kg/day was reported for inhibition of
      red blood cell (RBC) acetylcholinesterase (AChE) in two groups of Beagle dogs fed
      chlorpyrifos (0, 0.01, 0.03, 0.1, 1 or 3 mg/kg/day) in the diet for 1 or 2 years
      (McCollister et al., Food Cosmet. Toxicol. 12 (1974) 45-61). The statistical
      analyses were by t-test that had low statistical power due to small sample sizes.
      Common time points for blood samples in both phases allowed a reanalysis of the
      grouped data over a 1-year time period. The reanalysis increased statistical
      power by increasing the sample size to n=14 from n=3 or 4, and decreasing the
      variance, by statistical step-by-step aggregation of the data from both phases,
      both sexes, and four sample periods. Factors retained in the ANOVA were dose,
      sex, and phase (sex-by-dose was not significant). Contrasts with one-sided t
      tests indicated the 1 and 3 mg/kg/day groups had significantly inhibited RBC AChE
      (P<0.0001). At alpha=0.05, the uncorrected one-sided model had 80% power to
      detect a 12% decrease, 93% power for a 15% decrease, and 99.5% power for a 20%
      decrease in AChE activity. Overall, the reanalysis had high power to detect a
      clinically significant decrease in RBC AChE activity, and substantiated the
      original NOEL for chronic treatment of dogs to dietary chlorpyrifos at 0.1
      mg/kg/day.

PMID- 11246136
TI  - Sites and mechanisms for uptake of gases and vapors in the respiratory tract.
AB  - Inhalation is a common route by which individuals are exposed to toxicants. The
      air contains a multitude of gases and vapors that are brought into the
      respiratory tract with each breath. Depending upon the physical and chemical
      characteristics of the toxicant, the respiratory tract can be considered as a
      target organ in addition to a portal of entry. Sufficient information is not
      always available on the fate or effects of an inhaled gas or vapor. Two
      physiochemical principles, water solubility and reactivity, can be used to
      predict the site of uptake of gases and vapors in the respiratory tract and
      potential mechanisms for reaction with respiratory tract tissue and absorption
      into the blood. Four model compounds, formaldehyde, ozone, dibasic esters, and
      butadiene are discussed as examples of how knowledge of aqueous solubility and
      chemical reactivity can help toxicologists predict sites and mechanisms by which
      inhaled gases and vapors interact with respiratory tract tissues.

PMID- 11246137
TI  - Factors modulating the epithelial response to toxicants in tracheobronchial
      airways.
AB  - As one of the principal interfaces between the organism and the environment, the
      respiratory system is a target for a wide variety of toxicants and carcinogens.
      The cellular and architectural complexity of the respiratory system appears to
      play a major role in defining the focal nature of the pulmonary response to
      environmental stressors. This review will address the biological factors that
      modulate the response of one of the major target compartments within the
      respiratory system, the tracheobronchial airway tree. Individual airway segments
      respond uniquely to toxic stress and this response involves not only the target
      cell population, e.g. epithelium, but also other components of the airway wall
      suggesting a trophic interaction within all components of the airway wall in
      maintaining steady state and responding to injury. A number of biological factors
      modulate the nature of the response, including: (1) metabolic potential at
      specific sites for activation and detoxification; (2) the nature of the local
      inflammatory response; (3) age of the organism at the time of exposure; (4)
      gender of the exposed organism; (5) history of previous exposure; and (6) species
      and strain of the organism exposed.

PMID- 11246138
TI  - Genomics-based identification of targets in pathogenic bacteria for potential
      therapeutic and diagnostic use.
AB  - The availability of numerous complete microbial genome sequences has profoundly
      altered our understanding of a number of fundamental biological processes. For
      example the enzymes involved in aminoacyl-tRNA (AA-tRNA) synthesis, the key
      process responsible for the accuracy of protein synthesis, have been found to be
      highly species-specific. In particular, a number of pathogens contain certain
      pathways of AA-tRNA synthesis that are unrelated to those found in their
      mammalian hosts. Since AA-tRNA synthesis is indispensable for cell viability, the
      discovery of pathogen-specific pathways and enzymes presents novel therapeutic
      and diagnostic targets. Here we will review recent advances in the elucidation of
      AA-tRNA synthesis pathways and discuss the possible pharmaceutical exploitation
      of these discoveries. In particular, the integration of genomic and biochemical
      approaches to identify novel targets for the treatment of Chlamydial infections
      and the diagnosis and treatment of Lyme disease will be presented.

PMID- 11246139
TI  - Paracelsus, Haber and Arndt.
AB  - After a brief overview of the contributions of Paracelsus, Haber and Arndt to the
      theory of toxicology, examples are provided for quantitative risk/safety
      assessments using dose (c), time (t) and effect (E) as macroscopic variables of
      toxicity. The discussion offers explanations for application of the decision tree
      approach in identifying rate-determining steps in the toxicity of chemicals.
      Having done so allows for reasonably accurate predictions of cancer incidence
      (bladder, liver, heart, histiocyte) using Haber's Product under isoeffective
      conditions and the equation cxt=kxE for isodosic and isotemporal responses.

PMID- 11246140
TI  - Studies using structural analogs and inbred strain differences to support a role
      for quinone methide metabolites of butylated hydroxytoluene (BHT) in mouse lung
      tumor promotion.
AB  - Chronic treatment of BALB and GRS mice with BHT (2,6-di-tert-butyl-4
      methylphenol) following a single urethane injection increases lung tumor
      multiplicity, but this does not occur in CXB4 mice. Previous data suggest that
      promotion requires the conversion of BHT to a tert-butyl-hydroxylated metabolite
      (BHTOH) in lung and the subsequent oxidation of this species to an electrophilic
      quinone methide. To obtain additional evidence for the importance of quinone
      methide formation, structural analogs that form less reactive quinone methides
      were tested and found to lack promoting activity in BHT-responsive mice. The
      possibility that promotion-unresponsive strains are unable to form BHTOH was
      tested by substituting this compound for BHT in the promotion protocol using CXB4
      mice. No promotion occurred, and in-vitro work demonstrated that CXB4 mice are,
      in fact, capable of producing BHTOH and its quinone methide, albeit in smaller
      quantities. Incubations with BALB lung microsomes and radiolabeled substrates
      confirmed that more covalent binding to protein occurs with BHTOH than with BHT
      and, in addition, BHTOH quinone methide is considerably more toxic to mouse lung
      epithelial cells than BHT quinone methide. These data are consistent with the
      hypothesis that a two-step oxidation process, i.e. hydroxylation and quinone
      methide formation, is required for the promotion of mouse lung tumors by BHT.

PMID- 11246141
TI  - Cigarette smoke impairs neutrophil respiratory burst activation by aldehyde
      induced thiol modifications.
AB  - Exposure to airborne pollutants such as tobacco smoke is associated with
      increased activation of inflammatory-immune processes and is thought to
      contribute to the incidence of respiratory tract disease. We hypothezised that
      cigarette smoke (CS) could synergize with activated inflammatory/immune cells to
      cause oxidative injury or result in the formation of unique reactive oxidants.
      Isolated human neutrophils were exposed to gas-phase CS, and the production of
      nitrating and chlorinating oxidants following neutrophil stimulation was
      monitored using the substrate 4-hydroxyphenylacetate (HPA). Stimulation of
      neutrophils in the presence of CS resulted in a reduced oxidation and
      chlorination of HPA, suggesting inhibition of NADPH oxidase or myeloperoxidase
      (MPO), the two major enzymes involved in inflammatory oxidant formation.
      Peroxidase assays demonstrated that neutrophil MPO activity was not significantly
      affected after CS-exposure, leaving the NADPH oxidase as a likely target. The
      inhibition of neutrophil oxidant formation was found to coincide with depletion
      of cellular GSH, and a similar modification of critical cysteine residues, such
      as those in NADPH oxidase components, might be involved in reduced respiratory
      burst activity. As alpha,beta-unsaturated aldehydes such as acrolein have been
      implicated in thiol modifications by CS, we exposed neutrophils to acrolein prior
      to stimulation, and observed inhibition of NADPH oxidase activation in relation
      to GSH depletion. Additionally, translocation of the cytosolic components of
      NADPH oxidase to the membrane, a necessary requirement for enzyme activation, was
      inhibited. Protein adducts of acrolein (or related aldehydes) could be detected
      in several neutrophil proteins, including NADPH oxidase components, following
      neutrophil exposure to either CS or acrolein. Alterations in neutrophil function
      by exposure to (environmental) tobacco smoke may affect inflammatory/infectious
      conditions and thereby contribute to tobacco-related disease.

PMID- 11246142
TI  - Weight-of-evidence versus strength-of-evidence in toxicologic hazard
      identification: Di(2-ethylhexyl)phthalate (DEHP).
AB  - Toxicokinetic and mode of action data for DEHP reduce the concern for its
      potential carcinogenic hazard to human health. Chronic, high dose ingestion of
      DEHP and related peroxisome proliferators (PP) by mice and rats precipitate the
      following: activation of peroxisome proliferator activated receptor (PPARalpha)
      and its binding to peroxisome proliferator response elements (PPREs) within
      promoters of PP-responsive genes, peroxisome proliferation, increased microsomal
      fatty acid oxidation, increased hepatic hydrogen peroxide, hepatomegaly,
      hyperplasia and subsequent neoplasia. Neither peroxisome proliferation nor
      increased liver cancer occur in patients treated with pharmacologic doses of PP.
      Species differences in endogenous PPARalpha expression and differential activity
      of the peroxisome proliferator response element (PPRE) contribute to the failure
      of humans to respond in a manner qualitatively similar to that of rats or mice.
      Where it can be demonstrated that a mechanism for rodent tumor formation has no
      relevance for humans, then a substance which elicits a carcinogenic response in
      the test species via that mechanism should not be classified as anything other
      than an animal carcinogen. Systemic noncarcinogenic endpoints are available for
      definition of a DEHP reference dose. Considerable difficulty is encountered in
      the revision of promulgated regulations and in public risk communication when a
      material is no longer considered a carcinogenic hazard to humans.

PMID- 11246143
TI  - A concise review of the toxicity and carcinogenicity of dimethylarsinic acid.
AB  - Dimethylarsinic acid (DMA) has been used as a herbicide (cacodylic acid) and is
      the major metabolite formed after exposure to tri- (arsenite) or pentavalent
      (arsenate) inorganic arsenic (iAs) via ingestion or inhalation in both humans and
      rodents. Once viewed simply as a detoxification product of iAs, evidence has
      accumulated in recent years indicating that DMA itself has unique toxic
      properties. DMA induces an organ-specific lesion--single strand breaks in DNA--in
      the lungs of both mice and rats and in human lung cells in vitro. Mechanistic
      studies have suggested that this damage is due mainly to the peroxyl radical of
      DMA and production of active oxygen species by pulmonary tissues. Multi-organ
      initiation-promotion studies have demonstrated that DMA acts as a promotor of
      urinary bladder, kidney, liver and thyroid gland cancers in rats and as a
      promotor of lung tumors in mice. Lifetime exposure to DMA in diet or drinking
      water also causes a dose-dependent increase in urinary bladder tumors in rats,
      indicating that DMA is a complete carcinogen. These data collectively suggest
      that DMA plays a role in the carcinogenesis of inorganic arsenic.

PMID- 11246144
TI  - Global cosmetic regulatory harmonization.

PMID- 11246145
TI  - Mild prenatal stress enhances learning performance in the non-adopted rat
      offspring.
AB  - The present study was designed to investigate whether mild stress during
      pregnancy affects offspring behaviors, including learning performance. Prenatal
      stress was induced by short-lasting, mild restraint stress, which had previously
      been shown to facilitate the morphological development of fetal brain neurons.
      Adult offspring whose dams had been restrained in a small cage for 30min daily
      from gestation day 15 to 17 showed enhanced active avoidance and radial maze
      learning performance. In addition, the prenatally stressed rats showed weaker
      emotional responses than unstressed control, as indicated by decreases both in
      ambulation upon initial exposure to an open field and in Fos expression in the
      amygdala induced by physical stress. The observed effects of prenatal stress on
      learning performance and emotional behavior were attenuated by foster rearing by
      unstressed dams. Fos expression in the hypothalamic paraventricular nucleus
      following physical stress and corticosterone secretion during physical and
      psychological stress did not differ between the prenatally stressed and
      unstressed control rats. From these results we suggest that mild prenatal stress
      facilitates learning performance in the adult offspring. The enhancement of
      learning performance appears to be accompanied by reduced emotionality, but not
      by any apparent alterations in hypothalamic-pituitary-adrenal responses. In
      addition, the observation of differential behaviors in the adopted and non
      adopted animals supports the notion that the postnatal environment modifies the
      behavioral effects of prenatal stress.

PMID- 11246146
TI  - Involvement of protein kinase Cgamma isoform in morphine-induced reinforcing
      effects.
AB  - The present study was designed to investigate the role of protein kinase C (PKC)
      isoform in the morphine-induced reinforcing effect in mice. An
      intracerebroventricular injection of calphostin C, a specific PKC inhibitor,
      produced a dose-dependent reduction in the morphine-induced place preference. The
      protein level of PKCgamma was significantly up-regulated in membrane preparations
      of the limbic forebrain obtained from the morphine-conditioned mice compared to
      that from the saline-conditioned mice. However, the protein levels of PKCalpha,
      betaI, betaII and epsilon were not affected in the same preparation. By contrast,
      there were no changes in the protein level of all five PKC isoforms in the lower
      midbrain. Furthermore, we investigated the rewarding properties of morphine in
      mice lacking PKCgamma gene. A significant place preference was observed following
      treatment with morphine in wild-type mice, whereas such an effect of morphine was
      not found in PKCgamma knockout mice. These findings suggest that activated
      PKCgamma in the limbic forebrain following the treatment with morphine may be
      critical for the development and/or maintenance of reinforcing effects induced by
      morphine in mice.

PMID- 11246147
TI  - Structural and functional abnormalities of the hippocampal formation in rats with
      environmentally induced reductions in prepulse inhibition of acoustic startle.
AB  - The effects of social isolation on prepulse inhibition of acoustic startle (PPI),
      electrophysiology and morphology of subicular pyramidal neurons and the densities
      of interneuronal sub-types in the hippocampal formation were examined. Wistar
      rats (male weanlings) were housed socially (socials, n=8) or individually
      (isolates, n=7). When tested eight weeks later, PPI was lower in isolates. Rats
      then received terminal anaesthesia before slices of hippocampal formation were
      made in which the electrophysiological properties of a total of 108 subicular
      neurons were characterized. There were no differences in neuronal sub-types
      recorded in socials compared with isolates. Intrinsically burst-firing and
      regular spiking pyramidal neurons were examined in detail. There were no
      differences in resting membrane potential or input resistance in isolates
      compared with socials but action potential height was reduced and action
      potential threshold raised in isolates. A limited morphological examination of
      Neurobiotin-filled intrinsically burst-firing neurons did not reveal differences
      in cell-body area or in number of primary dendrites. Sections from the
      contralateral hemispheres of the same rats were stained with antibodies to
      calretinin, parvalbumin and the neuronal isoform of nitric oxide synthase (nNOS).
      In isolates, the density of calretinin positive neurons was increased in the
      dentate gyrus but unchanged in areas CA3, CA1 and subiculum. Parvalbumin and nNOS
      positive neuronal densities were unchanged. Hence in rats with environmentally
      induced reductions in PPI there are structural and functional abnormalities in
      the hippocampal formation. If the reduction in PPI stems from these
      abnormalities, and reduced PPI in rats is relevant to schizophrenia, then drugs
      that correct the reported electrophysiological changes might have antipsychotic
      effects.

PMID- 11246148
TI  - Hyperactivity and disruption of prepulse inhibition induced by N-methyl-D
      aspartate stimulation of the ventral hippocampus and the effects of pretreatment
      with haloperidol and clozapine.
AB  - This study re-examined the hyperactivity and disruption of prepulse inhibition
      induced by N-methyl-D-aspartate stimulation of the rat ventral hippocampus and
      compared how both effects were affected by pretreatment with either haloperidol
      or clozapine. While the hyperactivity is thought to depend on dopamine receptor
      activation in the nucleus accumbens, the dopamine D2-class receptor blocker
      haloperidol failed to antagonize the disruption of prepulse inhibition in
      previous studies. However, an ameliorative effect of the atypical neuroleptic
      clozapine on disruption of prepulse inhibition was suggested by our previous
      experiments [Zhang et al. (1999) NeuroReport 10, 1-6]. In the present study,
      bilateral infusion of N-methyl-D-aspartate (0.5microg/side) into the ventral
      hippocampus of Wistar rats increased open field locomotor activity and disrupted
      prepulse inhibition. Both effects were observed immediately after infusion but
      disappeared 24h later. Injection of haloperidol (0.2mg/kg) or clozapine (5mg/kg),
      45min prior to N-methyl-D-aspartate infusion, totally antagonized the
      hyperactivity but did not affect the disruption of prepulse inhibition. We
      conclude that dopaminergic mechanisms are differentially involved in the
      hyperactivity and disruption of prepulse inhibition induced by N-methyl-D
      aspartate stimulation of the ventral hippocampus. Activation of accumbal dopamine
      receptors, which is blocked by clozapine and haloperidol to a comparable extent,
      seems to be crucial for the hyperactivity but not the disruption of prepulse
      inhibition. The present finding that both clozapine and haloperidol failed to
      antagonize the disruption of prepulse inhibition induced by N-methyl-D-aspartate
      stimulation of the ventral hippocampus is discussed with respect to our previous
      contrary finding concerning the ameliorative effect of clozapine and with respect
      to the disruption of prepulse inhibition in rats being considered as a model of
      sensorimotor gating deficits in schizophrenia.

PMID- 11246149
TI  - Differential immunoreactivity for alpha-actinin-2, an N-methyl-D-aspartate
      receptor/actin binding protein, in hippocampal interneurons.
AB  - Recent studies have demonstrated that hippocampal interneurons possess distinct
      cytoskeletal and cell-signaling proteins in comparison to hippocampal principal
      cells; however, little is known about the differences in the actin cytoskeleton
      between these two populations. This study examined the immunoreactivity of alpha
      actinin-2, an actin binding/N-methyl-D-aspartate-receptor linking protein, in the
      rat hippocampal formation using double-labelling immunofluorescence. Alpha
      actinin-2 immunoreactivity is seen throughout the hippocampus with heavy labeling
      observed in the dendrites of granule cells, in CA2 pyramidal cells and in
      presumed interneuronal somata throughout the dentate gyrus and CA1. All the cells
      with heavy somatic alpha-actinin-2 immunoreactivity in the dentate gyrus and CA1
      were GABAergic interneurons labeled by glutamate decarboxylase (99%). Examination
      of the neurochemical marker content of the alpha-actinin-2 immunoreactive
      interneurons revealed that the majority of this population was neuropeptide-Y
      positive and a minority was positive for calretinin. Fluid percussion head trauma
      did not result in significant alterations of alpha-actinin-2 immunoreactivity in
      hippocampal interneurons. The developmental profile of alpha-actinin-2
      immunoreactivity showed the presence of alpha-actinin-2 in the hippocampus at P1,
      labeling of interneurons by P7 and the adult staining pattern seen by P21. This
      study demonstrates that principal cells and interneurons are differentially
      immunoreactive for alpha-actinin-2, and that alpha-actinin-2 staining is
      restricted to a subpopulation of interneurons. Each of the three classes of
      cytoskeletal elements have been shown to be differentially expressed in
      hippocampal interneurons and principal cells, suggesting that the cytoskeleton is
      a defining feature of neuronal populations. Additionally, the limited expression
      of alpha-actinin-2 could have important functional implications in N-methyl-D
      aspartate receptor localization and modulation.

PMID- 11246150
TI  - Dahl salt-sensitive and salt-resistant rats: examination of learning and memory
      performance, blood pressure, and the expression of central nicotinic
      acetylcholine receptors.
AB  - Substantial human and animal data suggest a correlation between hypertension and
      memory impairment that may appear prior to overt manifestations of
      cerebrovascular pathology. It is unclear, however, whether hypertension plays a
      causal role in these memory deficits, whether hypertension and cognitive
      impairment are each based in family history and not interdependent, or whether a
      combination of these factors is important. The purpose of this study was to
      assess whether deficits in memory performance and nicotinic acetylcholine
      receptors were present in Dahl salt-sensitive rats (as observed previously in
      spontaneously hypertensive rats) and whether the presence of hypertension per se
      (induced with an 8% Na(+) diet) contributed to the deficits. Memory was assessed
      in a passive avoidance task, an eight-arm radial arm maze and in a water maze
      task, and nicotinic receptors were measured via quantitative receptor
      autoradiography utilizing [125I]alpha-bungarotoxin and [3H]epibatidine. Salt
      sensitive rats exhibited impaired performance in both spatial learning tasks, but
      not the passive avoidance task, compared to controls (salt-resistant strain) and
      they exhibited reductions in nicotinic receptors labeled by [125I]alpha
      bungarotoxin but not [3H]epibatidine in some brain regions, including some areas
      important for memory (e.g. the hippocampus and amygdala). In the radial arm maze,
      the degree of memory impairment and in binding studies the reduced expression of
      nicotinic receptors each failed to correlate with the highest blood pressures,
      and the salt-sensitive animals were impaired relative to controls whether or not
      the high Na(+) diet was administered. In contrast, higher blood pressures did
      correlate with inferior task performance in the water maze. These findings may
      suggest that the genetics of the subjects were critical for performance when
      appetitive drives were involved, but diet (and perhaps hypertension) were key to
      performance when memory did not involve appetitive drives or mechanisms. Overall,
      the data obtained from Dahl rats appear to support the role of family history
      (selective breeding in rats) as underlying the reductions in central nicotinic
      acetylcholine receptors, whereas both family history and hypertension may
      contribute to poor cognitive performance.

PMID- 11246151
TI  - Glucose plus choline improve passive avoidance behaviour and increase hippocampal
      acetylcholine release in mice.
AB  - The present study tests the effects of glucose and choline, the biosynthetic
      precursors of acetylcholine, on passive avoidance behaviour and hippocampal
      acetylcholine release measured by microdialysis in awake mice. Glucose (10 and
      30mg/kg) or choline chloride (6-60mg/kg), given by i.p. injection immediately
      after training, dose-dependently enhanced retention in an inhibitory avoidance
      task. Combinations of low doses of glucose (10mg/kg) and choline chloride
      (20mg/kg) which alone were submaximally effective significantly increased
      retention latencies in a synergistic manner, an effect which was sensitive to
      atropine (0.5mg/kg). This beneficial effect vanished when higher doses of glucose
      or choline were combined. Basal hippocampal acetylcholine release in mice
      habituated to their environment was not affected by administration of glucose and
      choline. However, when hippocampal acetylcholine release was stimulated either by
      infusion of scopolamine (0.3microM) or by transferring the mice into a novel
      environment, the combination of glucose plus choline further increased
      acetylcholine release to a significant extent. We conclude that low doses of
      glucose and choline act synergistically to improve memory storage, an effect
      which is due to facilitation of acetylcholine release. This finding reinforces
      the view that central cholinergic functions are influenced under certain
      conditions by dietary intake of precursors.

PMID- 11246153
TI  - Tamoxifen abolishes estrogen's neuroprotective effect upon methamphetamine
      neurotoxicity of the nigrostriatal dopaminergic system.
AB  - The effects of 17beta-estradiol and the anti-estrogen, tamoxifen, on
      methamphetamine-induced neurotoxicity of the nigrostriatal dopaminergic system
      were examined in ovariectomized CD-1 mice. In Experiment 1, striatal dopamine
      concentrations from estrogen treated mice were significantly greater than that
      from non-estrogen treated mice following methamphetamine. Dopamine concentrations
      from estrogen+tamoxifen+methamphetamine treated mice were decreased compared to
      estrogen+methamphetamine treated mice and not significantly different from those
      of tamoxifen+methamphetamine treated mice or mice receiving methamphetamine
      alone. These results suggest that estrogen is functioning as a neuroprotectant of
      methamphetamine-induced nigrostriatal dopaminergic neurotoxicity and that this
      neuroprotective effect of estrogen is abolished in the presence of tamoxifen. In
      Experiment 2, estrogen administration after methamphetamine treatment did not
      produce any significant changes in dopamine concentrations compared with
      methamphetamine treatment alone. The data from Experiment 2 show that estrogen
      cannot reverse the methamphetamine-induced neurotoxicity upon the nigrostriatal
      dopaminergic system. Similar results were observed for the potassium-stimulated
      dopamine outputs from these treatment conditions as evaluated with in vitro
      superfusion, although a difference between the two measures for the
      estrogen+methamphetamine treated group was obtained in Experiment 1. These
      results have important implications for estrogen-tamoxifen interactions upon the
      nigrostriatal dopaminergic system and the gender differences which are observed
      in Parkinson's disease and animal models of nigrostriatal dopaminergic
      neurotoxicity as well as for the proposed use of tamoxifen in pre-menopausal
      women at risk for breast cancer.

PMID- 11246152
TI  - Protein oxidation in the brain in Alzheimer's disease.
AB  - In this study we used immunohistochemistry and two-dimensional fingerprinting of
      oxidatively modified proteins (two-dimensional Oxyblot) together to investigate
      protein carbonyl formation in the Alzheimer's disease brain. Increased protein
      oxidation was detected in sections from the hippocampus and parahippocampal
      gyrus, superior and middle temporal gyri of six Alzheimer's disease and six age
      matched control human subjects, but not in the cerebellum. In two brain regions
      severely affected by Alzheimer's disease pathology, prominent protein carbonyl
      immunoreactivity was localized in the cytoplasm of neurons without visual
      pathomorphological changes and degenerating neurons, suggesting that
      intracellular proteins might be significantly affected by oxidative
      modifications. Following two-dimensional electrophoresis the positions of some
      individual proteins were identified using specific antibodies, and immunoblot
      analysis for protein carbonyls was performed. These studies demonstrated the
      presence of protein carbonyl immunoreactivity in beta-tubulin, beta-actin and
      creatine kinase BB in Alzheimer's disease and control brain extracts. Protein
      carbonyls were undetectable in spots matching glial fibrillary acidic protein and
      tau isoforms. Specific protein carbonyl levels in beta-actin and creatine kinase
      BB were significantly higher in Alzheimer's disease than in control brain
      extract. beta-Tubulin did not demonstrate a significant increase in specific
      protein carbonyl content in Alzheimer's disease brains. We suggest that oxidative
      stress-induced injury may involve the selective modification of different
      intracellular proteins, including key enzymes and structural proteins, which
      precedes and may lead to the neurofibrillary degeneration of neurons in the
      Alzheimer's disease brain.

PMID- 11246154
TI  - Stimulation of metabotropic but not ionotropic glutamatergic receptors in the
      nucleus accumbens is required for the D-amphetamine-induced release of functional
      dopamine.
AB  - We have previously shown that a large part of the D-amphetamine-induced release
      of dopamine in the nucleus accumbens is not associated with an increase in
      locomotor activity, and that "functional" dopamine release (i.e. release of
      dopamine associated with locomotor activity) requires the distal facilitation of
      noradrenergic transmission through alpha1-adrenergic receptors in the prefrontal
      cortex. To determine the role of monosynaptic or polysynaptic projections from
      the prefrontal cortex to the nucleus accumbens in these amphetamine responses,
      either AMPA/kainate (6-cyano-7-nitroquinoxaline-2,3-dione, CNQX, 300microM), N
      methyl-D-aspartate (D(-)-2-amino-5-phosphono-pentanoic acid, APV, 500microM) or
      metabotropic [(+)-alpha-methyl-4-carboxy-phenylglycine, MCPG, 10mM] glutamate
      receptor antagonists were infused through a dialysis probe in the rat nucleus
      accumbens. CNQX and MCPG but not APV reduced the "non-functional" release of
      dopamine evoked by local (3microM) and systemic D-amphetamine (2mg/kg i.p.)
      treatments. However, the locomotor hyperactivity and functional dopamine release
      induced by systemic D-amphetamine were abolished by MCPG, but neither by CNQX nor
      by APV. MCPG treatment also abolished the hyperlocomotor activity and functional
      dopamine release evoked by bilateral morphine injection into the ventral
      tegmental area. The dopamine release evoked by this morphine treatment was 16
      fold lower than that induced by the systemic D-amphetamine injection, although
      similar behavioral activations were observed. Altogether, our results further aid
      the discrimination of functional and non-functional release of dopamine. We
      suggest that the activation of metabotropic glutamate receptors in the nucleus
      accumbens is required for functional dopamine release following systemic D
      amphetamine injection.

PMID- 11246155
TI  - Unilateral dopamine depletion increases expression of the 2A subunit of the N
      methyl-D-aspartate receptor in enkephalin-positive and enkephalin-negative
      neurons.
AB  - Striatal efferent neurons receive dopamine- and glutamate-utilizing afferents.
      Previous studies have shown that dopamine depletion increases gene expression in
      striatopallidal neurons and decreases it in striatonigral neurons. Previous work
      has also reported increased expression of the 2A subunit of the N-methyl-D
      aspartate receptor in the dopamine-depleted striatum. The purpose of this study
      therefore was to determine whether dopamine depletion differentially alters the
      expression of the 2A subunit of the N-methyl-D-aspartate receptor in rat striatal
      neurons. 6-Hydroxydopamine (8microg/2microl) was infused unilaterally into the
      medial forebrain bundle. Rats were killed three weeks later. Double-label in situ
      hybridization was performed using an 35S-labeled ribonucleotide probe directed
      against the messenger RNA of the 2A subunit and a digoxigenin-labeled
      ribonucleotide probe directed towards preproenkephalin messenger RNA to mark
      striatopallidal neurons. Analysis of single-labeled film autoradiograms revealed
      a significant increase in the expression of 2A subunit messenger RNA in the
      ipsilateral, but not the contralateral, striatum of dopamine-depleted animals,
      consistent with other studies in the literature. Cellular analysis of 2A subunit
      expression indicated that as a consequence of dopamine depletion there is a
      significant increase in the expression of this subunit in both enkephalin
      positive and enkephalin-negative neurons. From this study we conclude that
      dopamine depletion increases messenger RNA expression of the 2A subunit of the N
      methyl-D-aspartate receptor in striatopallidal and presumed striatonigral
      (enkephalin-negative) neurons. Such alterations may affect the pharmacology and
      function of the resultant receptor, and thus alter glutamate transmission in both
      populations of medium spiny neurons after dopamine depletion.

PMID- 11246156
TI  - Cholinergic neurons expressing neuromedin K receptor (NK3) in the basal forebrain
      of the rat: a double immunofluorescence study.
AB  - By using a double immunofluorescence method we have examined the distribution of
      cholinergic neurons expressing neuromedin K receptor (NK3) in the rat brain and
      spinal cord. The distribution of neuromedin K receptor-like immunoreactive
      neurons completely overlapped with that of choline acetyltransferase-positive
      neurons in certain regions of the basal forebrain, e.g. the medial septal
      nucleus, nucleus of the diagonal band of Broca, magnocellular preoptic nucleus
      and substantia innominata. Partially overlapping distributions of neuromedin K
      receptor-like immunoreactive and choline acetyltransferase-positive neurons were
      found in the basal nucleus of Meynert, globus pallidus, ventral pallidum of the
      forebrain, tegmental nuclei of the pons and dorsal motor nucleus of the vagus.
      Neurons showing both neuromedin K receptor-like and choline acetyltransferase
      immunoreactivities, however, were found predominantly in the medial septal
      nucleus, nucleus of the diagonal band of Broca and magnocellular preoptic nucleus
      of the basal forebrain: 66-80% of these choline acetyltransferase-positive
      neurons displayed neuromedin K receptor-like immunoreactivity. Neurons showing
      both neuromedin K receptor-like and choline acetyltransferase immunoreactivities
      were hardly detected in other aforementioned regions of the forebrain, brainstem
      and spinal cord. The present study has provided morphological evidence for direct
      physiological modulation or regulation of cholinergic neurons by tachykinins
      through the neuromedin K receptor in the basal forebrain of rats.

PMID- 11246157
TI  - Distribution of galanin messenger RNA-expressing cells in murine brain and their
      regulation by leptin in regions of the hypothalamus.
AB  - Galanin is widely distributed throughout the mammalian brain and has been
      implicated in the regulation of food intake, metabolism and reproduction
      functions that are also thought to be under the control of leptin. To investigate
      the possible role of galanin in mediating the physiological effects of leptin in
      the mouse, we had three experimental objectives: first, to map the distribution
      of galanin messenger RNA-expressing cells in the brain of the mouse; second, to
      assess the effects of leptin on galanin gene expression in areas of the brain
      thought to be involved in the regulation of body weight and reproduction; and
      third, to determine whether galanin neurons in these regions express leptin
      receptor messenger RNA. We found the pattern of galanin messenger RNA expression
      in the mouse brain to be similar, but not identical, to that in the rat. Leptin
      treatment (2microg/g for six days) significantly reduced cellular levels of
      galanin messenger RNA in the hypothalamic periventricular nucleus of leptin
      deficient obese (ob/ob) mice (P<0.01) by approximately 30%; however, leptin did
      not appear to influence the expression of galanin in the arcuate or dorsomedial
      nucleus of the hypothalamus. Galanin-producing neurons in the arcuate,
      dorsomedial and periventricular nuclei did not appear to express leptin receptor
      messenger RNA (P>0.05). These results demonstrate that galanin distribution
      patterns in the mouse brain are comparable to other species and, yet, possess
      unique features. In addition, galanin-expressing neurons in the hypothalamic
      periventricular nucleus are targets for regulation by leptin; however, the effect
      of leptin on galanin gene expression is likely to be mediated indirectly, perhaps
      through either proopiomelanocortin- or neuropeptide Y-expressing cells in the
      hypothalamus.

PMID- 11246158
TI  - Pituitary adenylate cyclase-activating polypeptide induces period1 and period2
      gene expression in the rat suprachiasmatic nucleus during late night.
AB  - The suprachiasmatic nucleus generates circadian rhythms which are synchronized to
      the environmental light-dark cycle via the retinohypothalamic tract. Pituitary
      adenylate cyclase-activating polypeptide and glutamate, two neurotransmitters co
      stored in the retinohypothalamic tract of the rat, are able to phase shift the
      endogenous rhythm similar to light. The "clock genes" period1 (per1) and per2,
      which show circadian oscillation within the suprachiasmatic nucleus, have been
      attributed a role in light-induced resetting of the mammalian circadian clock due
      to rapid induction of the period (per) genes after light stimulation at night.
      Using a rat in vitro brain slice model, we demonstrate by quantitative in situ
      hybridization histochemistry that the diurnal alteration in expression of both
      per genes in the suprachiasmatic nucleus was retained in vitro. In the model, we
      examined the effects of pituitary adenylate cyclase-activating polypeptide and
      glutamate alone and in combination on per1 and per2 gene expression at late
      subjective night (circadian time 19). Glutamate administration (10(-3)M) induced
      both per1 and per2 gene expression in the suprachiasmatic nucleus of the brain
      slice within 1h. The per gene responses were similar to the induction of gene
      expression observed after light stimulation in vivo at late night. Pituitary
      adenylate cyclase-activating polypeptide (10(-6)M) administered alone had no
      effect on the per gene expression, but when pituitary adenylate cyclase
      activating polypeptide in micromolar concentration was applied before glutamate,
      the neuropeptide blocked the glutamate-induced per1 and per2 gene expression in
      the suprachiasmatic nucleus. In contrast to the lack of effect of pituitary
      adenylate cyclase-activating polypeptide itself in micromolar concentration,
      pituitary adenylate cyclase-activating polypeptide (10(-9)M) induced both per1
      and per2 gene expression, an effect which was not augmented by co-application of
      glutamate. Our results provide the molecular substrate for the previous
      electrophysiological findings that pituitary adenylate cyclase-activating
      polypeptide in high concentration is able to block glutamate-induced phase
      advance at late night, and that the peptide in low concentration can induce a
      phase advance similar to light and glutamate.

PMID- 11246159
TI  - Expression of messenger RNAs for glutamic acid decarboxylase, preprotachykinin,
      cholecystokinin, somatostatin, proenkephalin and neuropeptide Y in the adult rat
      superior colliculus.
AB  - The mammalian superior colliculus is an important subcortical integrator of
      sensorimotor behaviours. It is multi-layered, each layer containing specific
      neuronal types and possessing distinct input/output relationships. Here we use in
      situ hybridisation methods to map the distribution of seven
      neurotransmitters/neuromodulator systems in adult rat superior colliculus.
      Coronal sections were probed for preprotachykinin, cholecystokinin, somatostatin,
      proenkephalin, neuropeptide Y and the enzymes glutamic acid decarboxylase and
      choline acetyltransferase, markers for GABA and acetylcholine respectively. Cells
      expressing glutamic acid decarboxylase messenger RNA were the most abundant, the
      highest density being found in the superficial layers. Many cells containing
      proprotachykinin messenger RNA were found in stratum zonale and the upper two
      thirds of stratum griseum superficiale; cells were also located in deeper tectal
      laminae, particularly caudomedially. Most cholecystokinin messenger RNA
      expressing cells were located in the superficial layers with a prominent band in
      the middle third of stratum griseum superficiale. Cells expressing moderate to
      high levels of somatostatin messenger RNA formed a dense band in the lower third
      of stratum griseum superficiale/upper stratum opticum; two less distinct tiers of
      labelling were seen in deeper layers. These in situ hybridisation data reveal
      three distinct sub-laminae in rat stratum griseum superficiale. Cells expressing
      moderate to low levels of proenkephalin messenger RNA were located in lower
      stratum griseum superficiale/upper stratum opticum and intermediate laminae. A
      cluster of enkephalinergic cells was located medially in the deep tectal laminae.
      Expression of neuropeptide Y messenger RNA was relatively low and mostly confined
      to cells in stratum griseum superficiale and stratum opticum. No choline
      acetyltransferase messenger RNA was detected. This in situ analysis of seven
      different neurotransmitters/neuromodulator systems sheds new light on the
      neurochemical organisation of the rat superior colliculus. The data are related
      to what is known anatomically and physiologically about intrinsic and extrinsic
      tectal circuitry, and the potential involvement of different neuropeptides in
      these circuits is discussed. The work forms the basis for future developmental
      studies examining the effects of transplantation and visual
      deprivation/deafferentation on tectal neurochemistry and function.

PMID- 11246160
TI  - Nitric oxide in the afferent synaptic transmission of the axolotl vestibular
      system.
AB  - This study was performed using intracellular and multiunit extracellular
      recording techniques in order to characterize the role of nitric oxide in the
      afferent synaptic transmission of the vestibular system of the axolotl (Ambystoma
      tigrinum). Bath application of nitric oxide synthase inhibitors N(G)-nitro-L
      arginine (0.01microM to 10microM) and N-nitro-L-arginine methyl ester
      hydrochloride (0.1microM to 1000microM) elicited a dose-dependent decrease in the
      basal discharge of the semicircular canal afferent fibers. N(G)-Nitro-L-arginine
      also diminished the response to mechanical stimuli. Moreover, N(G)-nitro-L
      arginine (1microM) produced a hyperpolarization associated with a decrease in the
      spike discharge and diminished the frequency of the excitatory postsynaptic
      potentials on afferent fibers recorded intracellularly. Nitric oxide donors were
      also tested: (i) S-nitroso-N-acetyl-DL-penicillamine (0.1microM to 100microM)
      increased the basal discharge and the response to mechanical stimuli. At the
      maximum effective concentration (100microM) this drug affected neither the
      amplitude nor the frequency of the excitatory postsynaptic potentials. However,
      it slightly depolarized the afferent neurons and decreased their input
      resistance. (ii) 3-Morpholino-sydnonimine hydrochloride did not significantly
      affect the basal discharge or the mechanically evoked peak response of afferent
      neurons at any of the concentrations used (1microM to 1000microM). However, after
      10min of perfusion in the bath, 1microM and 10microM 3-morpholino-sydnonimine
      hydrochloride significantly modified the baseline of the mechanically evoked
      response, producing an increase in the mean spike discharge of the afferent
      fibers. These results indicate that nitric oxide may have a facilitatory role on
      the basal discharge and on the response to mechanical stimuli of the vestibular
      afferent fibers. Thus, nitric oxide probably participates in the sensory coding
      and adaptative changes of vestibular input in normal and pathological conditions.

PMID- 11246161
TI  - Neuronal BC1 RNA: co-expression with growth-associated protein-43 messenger RNA.
AB  - Brain-specific cytoplasmic RNA 1 (BC1-RNA), a non-coding RNA polymerase III
      transcript, is a neuronal RNA that is specifically targeted to dendritic domains.
      It is co-localized with components of the dendritic protein synthetic machinery,
      and it has been suggested to operate in the regulation of local translation
      related processes in postsynaptic microdomains, thus subserving long-term
      synaptic plasticity in neurons. To probe the relevance of BC1 expression in
      neuronal plasticity, we have analyzed the expression pattern of BC1 RNA in the
      rat nervous system. We found that BC1 RNA is expressed by a specific subset of
      neurons (but not by non-neuronal cells) in the central and peripheral nervous
      system of the adult rat. The BC1 labeling pattern indicates that the subcellular
      location of the RNA is typically postsynaptic which, depending on cell type,
      manifests itself in a predominantly somatic, somatodendritic, or dendritic
      location. Our results further show that BC1-expressing neurons typically co
      express the messenger RNA for growth-associated protein-43 (GAP-43). Such co
      expression was observed in diverse brain areas, including the olfactory bulb,
      neocortex, and hippocampus, among others. While BC1 RNA was in many neuronal cell
      types detectable in distal dendritic domains, GAP-43 messenger RNA was typically
      more restricted to neuronal perikarya. In the mature nervous system, expression
      of GAP-43 has been described as an intrinsic determinant of predominantly
      presynaptic plasticity, while BC1 RNA has been implicated in postsynaptic
      plasticity. Co-expression of both RNAs, as reported here, thus identifies a
      distinct subset of neurons in the rat nervous system that exhibits both types of
      plasticity.

PMID- 11246162
TI  - Localization of the K(+)-Cl(-) cotransporter, KCC3, in the central and peripheral
      nervous systems: expression in the choroid plexus, large neurons and white matter
      tracts.
AB  - Na(+)-independent K(+)-Cl(-) cotransporters function in the regulation of cell
      volume, control of CNS excitability and epithelial ion transport. Several K(+)
      Cl(-) cotransporter isoforms are expressed in the nervous system, and KCC3 in
      particular is expressed at significant levels in both the brain and spinal cord.
      The cellular localization of this transporter has, however, not been determined.
      In this study, we generated a polyclonal antibody against the KCC3 cotransporter
      in order to characterize and localize this protein in the brain. Western blot
      analysis of mouse kidney and brain demonstrated KCC3 proteins of different size,
      150 and 170kDa, respectively; this disparity remained after deglycosylation.
      Northern blot confirmed the presence of two distinct forms of KCC3, KCC3a and
      KCC3b, generated by the inclusion of different first coding exons. KCC3a
      predominates in the brain, whereas KCC3b is more abundant in the kidney. Western
      blots with membrane protein from dissected mouse brain revealed abundant
      expression in all brain regions examined: the cerebral cortex, hippocampus,
      diencephalon, brainstem and cerebellum. The spinal cord showed the highest levels
      of KCC3 expression, whereas peripheral nerves did not contain immunoreactive KCC3
      protein. Western blot analysis of whole brain from rats of various ages indicated
      increasing expression in the postnatal period, concurrent with CNS maturation and
      myelination. Immunofluorescence studies demonstrated strong signal in myelinated
      tracts of the spinal cord, consistent with individual myelin sheaths. Brain
      sections also showed white matter enhancement, but also cellular signal
      consistent with pyramidal neurons and Purkinje cells. The base of the choroid
      plexus epithelium was also strongly labeled. These data demonstrate the
      specificity and diversity of KCC3 expression in the mouse CNS.

PMID- 11246163
TI  - Spinal cord genes enriched in rat dorsal horn and induced by noxious stimulation
      identified by subtraction cloning and differential hybridization.
AB  - Persistent nociceptive input increases neuronal excitability and induces a
      program of gene expression in the dorsal spinal cord. The alteration in gene
      expression commences with phosphorylation and induction of immediate early genes
      and proceeds to target genes. Only a few target genes have been identified as
      yet. The present report uses a polymerase chain reaction-based subtraction
      cloning procedure to obtain an "anatomically focused" complementary DNA library
      enriched in transcripts related to sensory spinal cord (rat dorsal horn minus
      ventral horn). A subset of clones from this library (n=158) was screened to
      verify dorsal horn enrichment and to identify those regulated by carrageenan
      induced peripheral inflammation. Molecular classes which displayed enriched
      expression included a proto-oncogene not previously associated with sensory
      processes, two regulators of the Rho/Rac pathway which controls cell shape, and
      three genes involved in cytoskeletal regulation and scaffolding. Additional
      transcripts coded for proteins involved in intercellular communication or
      intracellular function. Within the set of 158 transcripts, one known and two
      unknown genes were induced by persistent noxious input. The known gene codes for
      the secreted cysteine proteinase inhibitor, cystatin C, suggesting that
      modulation of extracellular proteolytic activity occurs. Since it is secreted,
      cystatin C may also provide a cerebrospinal fluid bio-marker for persistent pain
      states. Using a combined anatomical and functional approach, we have extended the
      molecular repertoire of genes expressed and induced in second-order neurons or
      supporting glial cells in several new directions, with particular emphasis on
      regulation of cell morphology and plasma membrane dynamics. Some of these
      proteins reveal new pathways for information signaling in the sensory half of the
      spinal cord and require further research to understand their role in the adult
      spinal cord. The induced genes may provide new molecular targets for therapeutic
      development and provide new probes for investigating the dynamic state of
      cellular activity that occurs during persistent pain states.

PMID- 11246164
TI  - Improved functional recovery of denervated skeletal muscle after temporary
      sensory nerve innervation.
AB  - Prolonged muscle denervation results in poor functional recovery after nerve
      repair. The possible protective effect of temporary sensory innervation of
      denervated muscle, prior to motor nerve repair, has been examined in the rat.
      Soleus and gastrocnemius muscles were denervated by cutting the tibial nerve, and
      the peroneal nerve was then sutured to the transected distal tibial nerve stump
      either immediately or after two, four or six months. In half of the animals with
      delayed repair, the saphenous (sensory) nerve was temporarily attached to the
      distal nerve stump. Muscles were evaluated three months after the peroneal-to
      tibial union, and were compared with each other, with unoperated control muscles
      and with untreated denervated muscles. After four to six months of sensory
      "protection", gastrocnemius muscles weighed significantly more than unprotected
      muscles, and both gastrocnemius and soleus muscles exhibited better preservation
      of their structure, with less fiber atrophy and connective tissue hyperplasia.
      The maximum compound action potentials were significantly larger in gastrocnemius
      and soleus muscles following sensory protection, irrespective of the delay in
      motor nerve union. Isometric force, although less than in control animals and in
      those with immediate nerve repair, remained reasonably constant after sensory
      protection, while in unprotected muscles there was a progressive and significant
      decline as the period of denervation lengthened. We interpret these results as
      showing that, although incapable of forming excitable neuromuscular junctions,
      sensory nerves can nevertheless exert powerful trophic effects on denervated
      muscle fibers. We propose that these findings indicate a useful strategy for
      improving the outcome of peripheral nerve surgery.

PMID- 11246165
TI  - Medullary reticulospinal tract mediating the generalized motor inhibition in
      cats: parallel inhibitory mechanisms acting on motoneurons and on interneuronal
      transmission in reflex pathways.
AB  - The present study was designed to elucidate the spinal interneuronal mechanisms
      of motor inhibition evoked by stimulating the medullary reticular formation. Two
      questions were addressed. First, whether there is a parallel motor inhibition to
      motoneurons and to interneurons in reflex pathways. Second, whether the
      inhibition is mediated by interneurons interposed in known reflex pathways. We
      recorded the intracellular activity of hindlimb motoneurons in decerebrate cats
      and examined the effects of medullary stimulation on these neurons and on
      interneuronal transmission in reflex pathways to them. Stimuli (three pulses at
      10-60microA and 1-10ms intervals) delivered to the nucleus reticularis
      gigantocellularis evoked inhibitory postsynaptic potentials in alpha-motoneurons
      (n=147) and gamma-motoneurons (n=5) with both early and late latencies. The early
      inhibitory postsynaptic potentials were observed in 66.4% of the motoneurons and
      had a latency of 4.0-5.5ms with a segmental delay of more than 1.4ms. The late
      inhibitory postsynaptic potentials were observed in 98.0% of the motoneurons and
      had a latency of 30-35ms, with a peak latency of 50-60ms. Both types of
      inhibitory postsynaptic potentials were evoked through fibers descending in the
      ventrolateral quadrant. The inhibitory postsynaptic potentials were not
      influenced by recurrent inhibitory pathways, but both types were greatly
      attenuated by volleys in flexor reflex afferents. Conditioning medullary
      stimulation, which was subthreshold to evoke inhibitory postsynaptic potentials
      in the motoneurons, neither evoked primary afferent depolarization of dorsal
      roots nor reduced the input resistance of the motoneurons. However, the
      conditioning stimulation often facilitated non-reciprocal group I inhibitory
      pathways (Ib inhibitory pathways) to the motoneurons in early (<20ms) and late
      (30-80ms) periods. In contrast, it attenuated test postsynaptic potentials evoked
      through reciprocal Ia inhibitory pathways, and excitatory and inhibitory pathways
      from flexor reflex afferent and recurrent inhibitory pathways. The inhibitory
      effects were observed in both early and late periods. The present results provide
      new information about a parallel inhibitory process from the medullary reticular
      formation that produces a generalized motor inhibition by acting on alpha- and
      gamma-motoneurons, and on interneurons in reflex pathways. Interneurons receiving
      inhibition from flexor reflex afferents and a group of Ib interneurons may
      mediate the inhibitory effects upon motoneurons.

PMID- 11246166
TI  - Intrathecal interleukin-1 receptor antagonist in combination with soluble tumor
      necrosis factor receptor exhibits an anti-allodynic action in a rat model of
      neuropathic pain.
AB  - The expression of interleukin-1beta and tumor necrosis factor has previously been
      shown to be up-regulated in the spinal cord of several rat mononeuropathy models.
      This present study was undertaken to determine whether blocking the action of
      central interleukin-1beta and tumor necrosis factor attenuates mechanical
      allodynia in a gender-specific manner in a rodent L5 spinal nerve transection
      model of neuropathic pain, and whether this inhibition occurs via down-regulation
      of the central cytokine cascade or blockade of glial activation. Interleukin-1
      receptor antagonist or soluble tumor necrosis factor receptor was administered
      intrathecally via lumbar puncture to male Holtzman rats in a preventative pain
      strategy, in which therapy was initiated 1h prior to surgery. Administration of
      soluble tumor necrosis factor receptor attenuated mechanical allodynia, while
      interleukin-1 receptor antagonist alone was unable to decrease allodynia.
      Interleukin-1 receptor antagonist in combination with soluble tumor necrosis
      factor receptor, administered to both male and female rats in a preventative pain
      strategy, significantly reduced mechanical allodynia in a dose-dependent manner
      (P<0.01). The magnitude of attenuation in allodynia was similar in both males and
      females. Immunohistochemistry on L5 spinal cord revealed similar astrocytic and
      microglial activation regardless of treatment. At days 3 and 7 post-transection,
      animals receiving daily interleukin-1 receptor antagonist in combination with
      soluble tumor necrosis factor receptor exhibited significantly less interleukin
      6, but not interleukin-1beta, in the L5 spinal cord compared to vehicle-treated
      animals. In an existing pain paradigm, in which treatment was initiated on day 7
      post-transection, interleukin-1 receptor antagonist in combination with soluble
      tumor necrosis factor receptor attenuated mechanical allodynia (P<0.05) in male
      rats. These findings further support a role for central interleukin-1beta and
      tumor necrosis factor in the development and maintenance of neuropathic pain
      through induction of a proinflammatory cytokine cascade.

PMID- 11246167
TI  - alpha7-Containing nicotinic receptors are segregated to the somatodendritic
      membrane of the cholinergic neurons in the avian nucleus semilunaris.
AB  - Segregation of ion channels and neurotransmitter receptors is an important
      mechanism for determining the functionality of the nervous system. In the case of
      nicotinic acetylcholine receptors, electrophysiological and anatomical studies
      have demonstrated that these receptors can be located at the somatodendritic and
      the axon terminal portions of neurons. Functionally, somatodendritic nicotinic
      receptors mediate fast excitatory transmission and possibly regulate other cell
      functions, while presynaptic nicotinic receptors enhance the release of
      neurotransmitters from axon terminals. Neurons in the mesencephalic lateral
      spiriform nucleus of the chick do not appear to restrict the localization of
      nicotinic receptors to specific membrane compartments, since receptors containing
      alpha5 and/or beta2 subunits are found both on the cell bodies and on the axonal
      projections of these neurons [Torrao A. S. et al. (1996) Brain Res. 743, 154
      161]. We report here that, in contrast to lateral spiriform neurons, neurons in
      the nucleus semilunaris do appear to compartmentalize nicotinic receptors. The
      cholinergic nucleus semilunaris neurons express a high density of alpha7
      containing nicotinic receptors on their somas [Britto L. R. G. et al. (1992) J.
      comp. Neurol. 317, 325-340]. However, when we examined the projections of these
      neurons in the lateral spiriform nucleus, we found no evidence for expression of
      alpha7-containing receptors on the cholinergic fibers from nucleus semilunaris
      neurons. Furthermore, patch-clamp electrophysiological recording from lateral
      spiriform neurons indicated an absence of presynaptic alpha7-containing nicotinic
      receptors capable of modulating the release of acetylcholine. We conclude that
      neurons are capable of segregating alpha7-containing nicotinic receptors to
      specific areas of their plasma membrane. Such targeting of nicotinic receptors
      would play an important role in determining their functional role in neurons.

PMID- 11246168
TI  - Up- and down-regulation of Helix command-specific 2 (HCS2) gene expression in the
      nervous system of terrestrial snail Helix lucorum.
AB  - A novel gene named Helix command-specific 2 (HCS2) was shown to be expressed
      predominantly in four giant parietal interneurons involved in withdrawal behavior
      of the terrestrial snail Helix lucorum L. and several single neurons in other
      ganglia. Decrease in spontaneous electrophysiological activity of neurons in the
      isolated CNS by 24h incubation in saline with elevated Mg(2+) concentration
      significantly decreased the number of HCS2-expressing neurons. Five short-term
      serotonin applications (each of 10microM), during a 24h incubation of the nervous
      system in saline induced expression of the HCS2 gene in many cells in cerebral,
      parietal, pleural and pedal ganglia. Dopamine applications under similar
      conditions were not effective. Application of anisomycin or cycloheximide, known
      to block protein synthesis, did not prevent the induction of HCS2 expression
      under serotonin influence. Skin injury elicited a significant increase in the
      number of HCS2-expressing cells 24h later in pleural and cerebral ganglia.
      Incubation of the isolated nervous system preparations for three days in culture
      medium elicited close to a maximum increase in number of HCS2-expressing cells.
      Elevation of the normal Mg(2+) concentration in the culture medium significantly
      decreased the number of cells demonstrating HCS2 expression. Application of the
      cAMP activator forskolin (10microM) increased the expression under Mg(2+),
      indicating that cAMP was involved in the up-regulation of HCS2. Application of
      thapsigargin (10microM), known to release Ca(2+) from intracellular stores, was
      also effective in increasing expression, suggesting participation of Ca(2+) in
      regulation of HCS2 expression. Cellular groups expressing the HCS2 gene under
      different conditions seem to be functionally related since it was demonstrated
      earlier that some neurons constituting these clusters are involved in the
      withdrawal behavior and the response of the organism to stress stimuli. From
      these results we suggest that the HCS2 pattern of expression can be down
      regulated by a decrease in synaptic activity in the nervous system, and up
      regulated by external noxious inputs, as well as the application of
      neurotransmitters and second messengers known to be involved in the withdrawal
      behavior and maintenance of isolated ganglia in culture medium. When up
      regulated, the HCS2 expression appears, at least in part in neurons, to be
      involved in the withdrawal behavior.

PMID- 11246169
TI  - Slow inhibitory potentials in the teleost Mauthner cell.
AB  - In vivo recordings from Mauthner cells in adult zebrafish (Danio rerio) and
      goldfish (Carassius auratus) preparations with potassium chloride filled
      electrodes revealed a new class of long-lasting synaptic events in these cells.
      Their decay time constant ranged from 20 to 80ms, which is about 20 times longer
      than that of previously identified fast glycinergic inhibitory postsynaptic
      potentials in this neuron. The average time to peak of these slow events ranged
      from 1 to 6ms. We demonstrated that they are also inhibitory since (i) they were
      resistant to antagonists of the excitatory glutamatergic receptors; (ii) their
      amplitude was increased following chloride loading of the Mauthner cell; (iii)
      their reversal potential was the same as that of fast, glycinergic inhibitory
      postsynaptic potentials; and (iv) they produced an inhibitory shunt of the cell's
      membrane resistance. Furthermore, as with the fast inhibitory postsynaptic
      potentials, the decay time of the slow events is voltage dependent, increasing
      when the Mauthner cell is depolarized. However, these inhibitory postsynaptic
      potentials had a different pharmacological profile to the fast glycinergic ones.
      That is, they persisted in the presence of strychnine at doses that abolished the
      fast ones and they were more sensitive to bicuculline. These data are compatible
      with the notion that these inhibitory postsynaptic potentials are mediated by
      activation of a different inhibitory receptor type, and may be GABAergic. In
      addition, the decay time constant of the fast inhibitory postsynaptic current was
      shorter than the first of the two components that contribute to the bi
      exponential decay reported previously for miniature inhibitory postsynaptic
      currents in Mauthner cells of larval zebrafish. This suggests developmental
      modifications and/or a switch in the assembly of glycine receptor subtypes. While
      amplitude distributions of the fast miniature inhibitory postsynaptic potentials
      recorded in the presence of tetrodotoxin generally could fit with a single
      Gaussian function, the amplitude histograms of slow miniature events were skewed,
      often with multiple nearly equally spaced peaks, consistent with the synchronous
      release of several quantal units. These previously undescribed slow unitary
      inhibitory postsynaptic potentials contribute to inhibitory synaptic noise
      recorded in the Mauthner cells. Specifically, autocorrelation analysis revealed
      gamma-like rhythms (30-80Hz) in each of two phases, characterized as "noisy" and
      "quiet", and dominated by the fast and slow inhibitory postsynaptic potentials,
      respectively. The major frequencies of these two states were significantly
      different (i.e. around 90 and 40Hz, respectively), suggesting that the fast and
      slow inhibitory postsynaptic potentials are derived from different inhibitory
      networks. Chloride-filled Mauthner cells gradually hyperpolarized in the presence
      of tetrodotoxin, reflecting the effect of ongoing activity in the interneurons
      that produce the slow events. We conclude that this new class of inhibitory
      postsynaptic potentials contributes to the tonic inhibition which controls the
      Mauthner cell's excitability. In physiological conditions, this regulatory
      influence is expressed as a continuous shunt of this neuron's input resistance
      and responsiveness to sensory inputs.

PMID- 11246170
TI  - Role of corticosterone in ethyl carbamate-induced immunosuppression in female
      BALB/c mice.
AB  - We have recently demonstrated that the antibody response to the T-cell-dependent
      antigen, sheep red blood cells (SRBCs), was suppressed by ethyl carbamate in
      female BALB/c mice. At the same doses, ethyl carbamate decreased in the numbers
      of splenic macrophages, B cells, total T cells, CD4(+) T cells and CD8(+) T
      cells. In addition, the serum level of corticosterone was increased dose
      dependently. To investigate the possible role of corticosterone in ethyl
      carbamate-induced immunosuppression, the antibody response to SRBCs and the
      subpopulation changes of splenocytes and thymocytes were determined in naive,
      sham-operated and adrenalectomized (ADX) female BALB/c mice. When the mice were
      treated intraperitoneally with 400 mg/kg ethyl carbamate, the antibody response
      was significantly suppressed by ethyl carbamate in naive and sham-operated mice
      in accompanying the decrease in spleen and thymus weights and/or the increase in
      the level of serum corticosterone. Meanwhile, the antibody response was not
      suppressed by ethyl carbamate in the ADX mice. The splenic numbers of total
      cells, macrophages, B and T cells, and CD4(+) cells were decreased by ethyl
      carbamate in naive and sham-operated mice. Meanwhile, each cell number was
      comparable with control in the ADX mice. The flow cytometric analyses on
      thymocytes did not show obvious differences as seen in the spleen. Finally, when
      the ADX mice were treated intraperitoneally with 25 mg/kg corticosterone, the
      antibody response was significantly suppressed. Taken together, our present
      results suggested that corticosterone might be, at least partially, responsible
      for ethyl carbamate-induced immunosuppression in female BALB/c mice.

PMID- 11246171
TI  - Induction of delayed-type hypersensitivity to sulfamethoxazole in mice: role of
      metabolites.
AB  - Although cutaneous adverse drug reactions (ADRs) are relatively frequent and
      potentially severe, their mechanisms are poorly understood and no validated
      predictive experimental model is available. Sulfamethoxazole (SMX) is commonly
      used to treat infections in HIV-positive patients and severe cutaneous ADRs have
      been described. This study was undertaken to test whether sensitization to SMX
      could be achieved in mice using a combination of in vivo and in vitro endpoints.
      No delayed-type hypersensitivity (DTH) response could be evidenced following SMX
      injection in the back and subsequent challenge into the footpad or onto the ear.
      Pretreatment with the enzymatic inducers phenobarbitone and betanaphtoflavone, or
      depletion in CD4(+) T-lymphocytes were not successful either. In contrast, the
      injection of SMX/S9 mix in the back and challenge with SMX/S9 mix induced a
      significant increase in footpad thickness. A significant proliferation of spleen
      cells from SMX- or SMX/S9 mix-treated mice was evidenced following incubation
      with SMX/S9 mix, but not SMX alone. This study provides indirect evidence that
      SMX metabolites are involved and confirms previous in vitro results obtained with
      lymphocytes from patients with a history of SMX-induced ADRs cultured with murine
      microsomes. Further investigations using other drugs known to induce similar ADRs
      are warranted to establish the predictive value of this murine model.

PMID- 11246172
TI  - Effects of long-term exposure to manganese chloride on fertility of male and
      female mice.
AB  - The effect of long-term ingestion of manganese (II) chloride tetrahydrate was
      investigated on fertility of male and female Swiss mice. Adult male or female
      mice ingested a solution of manganese chloride along with drinking water at
      concentrations of 1000, 2000, 4000 and 8000 mg/l for 12 weeks. Fertility was
      significantly reduced in male mice exposed to manganese chloride solution at a
      concentration of 8000 mg/l, but not at the other concentrations. There were no
      treatment-related effects on the number of implantation sites, viable fetuses or
      the number of resorptions in female rats impregnated by males who had ingested
      manganese chloride. Fertility was not significantly reduced in female mice
      exposed to manganese chloride solution at all concentrations used in this study.
      However, the numbers of implantations and viable fetuses were significantly
      reduced in females exposed to manganese chloride solution at a concentration of
      8000 mg/l. There was no significant effect on the number of resorbed fetuses in
      females exposed to manganese chloride solution compared to their control
      counterparts. Absolute body weight was not significantly affected in females
      exposed to manganese chloride solutions. However, ovarian weight was
      significantly increased in females exposed to manganese chloride solution at
      concentrations of 4000 and 8000 mg/l. A significant increase in the uterine
      weight was also observed at all concentrations used in the study. These results
      indicate that ingestion of manganese chloride by adult male and female mice
      causes some adverse effects on fertility and reproduction.

PMID- 11246173
TI  - Development of non-radio isotopic endpoint of murine local lymph node assay based
      on 5-bromo-2'-deoxyuridine (BrdU) incorporation.
AB  - Allergic contact dermatitis is a serious health problem. Over the last decade,
      the murine local lymph node assay (LLNA) has been developed to detect chemical
      allergens, and international validation studies have been conducted. We have
      tried to establish an alternative non-radioisotopic endpoint for the LLNA by
      using 5-bromo-2'-deoxyuridine (BrdU) incorporation in place of radioisotopes,
      such as [3H]thymidine, employed in the standard method. BrdU was given as a
      single administration at 5 mg/animal 2 days following three consecutive daily
      applications of a test chemical. BrdU incorporation into draining lymph node
      cells was measured using an enzyme immunosorbent assay technique. In this study,
      p-benzoquinone(PBQ), trimellitic anhydride (TMA), citral(CT) and dextran (DEX)
      were used as pilot chemicals. PBQ, TMA and CT, which are classified as moderate
      to strong sensitizers in the guinea pig maximization test and were positive in
      the original LLNA, were also found to elicit positive responses in the
      alternative LLNA using BrdU incorporation. In contrast, DEX tested negative in
      the modified assay consistent with previous guinea pig and LLNA data.
      Consequently, the modified LLNA endpoint using BrdU incorporation may represent a
      useful alternative to the standard assay in situations, where there is a need to
      avoid the use of radioisotopes.

PMID- 11246175
TI  - Interaction of plasma proteins with cytochromes P450 mediated metabolic
      reactions: inhibition by human serum albumin and alpha-globulins of the
      debrisoquine 4-hydroxylation (CYP2D) in liver microsomes of human, hamster and
      rat.
AB  - The effect of human serum albumin (HSA), alpha1-acid glycoprotein (alpha1-AGP),
      and alpha- and gamma-globulins on the in vitro metabolism of debrisoquine in
      human, hamster and rat liver microsomes was studied. Interaction of albumin with
      cytochrome P450 mediated phenytoin metabolism has been reported. Since plasma
      protein binding of phenytoin is high, in the present study a weakly protein bound
      drug, debrisoquine, was studied. Debrisoquine is a substrate of CYP2D6. The
      debrisoquine 4-hydroxylation was measured using a radio-TLC method. Among the
      four plasma proteins, alpha-globulins had the strongest inhibitory effect on the
      debrisoquine 4-hydroxylase activity. The inhibition with 2% alpha-globulins was
      42+/-18% for human and higher for hamster and rat liver microsomes (65-71%). HSA
      had less effect than alpha-globulins. In the presence of HSA, the decrease in
      activity was between 18 and 35% for all liver microsomes studied. The
      debrisoquine 4-hydroxylase activity was not significantly changed by alpha1-AGP
      or gamma-globulins. Using an ultra-filtration method, the protein binding of
      debrisoquine to 4% HSA, 0.5% alpha1-AGP, 2% alpha-globulins and 2% gamma
      globulins was found to be 22, 20, 22 and 5%, respectively. Since the observed
      inhibition is inconsistent with level of protein binding, it appears,
      particularly in the case of alpha-globulins, that the plasma proteins interact
      with CYP2D directly.

PMID- 11246174
TI  - Cytokine induction as a measure of cutaneous toxicity in primary and immortalized
      porcine keratinocytes exposed to jet fuels, and their relationship to normal
      human epidermal keratinocytes.
AB  - The purpose of this study was to identify biomarkers of toxicity in primary
      porcine keratinocytes (PKC) and an immortalized porcine keratinocyte cell line
      (MSK3877) exposed to jet fuels Jet A, JP-8, and JP-8+100. Cells were exposed to
      0.1% jet fuels and assayed for interleukin-8 (IL-8) and tumor necrosis factor
      alpha (TNF-alpha) mRNA using the TaqMan real time quantitative reverse
      transcriptase PCR assay. IL-8 and TNF-alpha protein release was measured using an
      ELISA. PKC exposed to jet fuels caused a slight upregulation of TNF-alpha mRNA at
      early time points, but no significant differences in TNF-alpha protein production
      were detected. IL-8 mRNA was increased at 4 h following exposure, and IL-8
      protein was increased at 8 h. In MSK 3877 cells, jet fuels were shown to increase
      the production and expression of TNF-alpha mRNA and protein at 30 min and 1 h
      following exposure, respectively. IL-8 mRNA was only slightly induced compared to
      control. IL-8 protein release was suppressed by jet fuel exposure. These results
      were compared with those of a previous study in our laboratory to evaluate the
      utility of using porcine cells in lieu of normal human epidermal keratinocytes
      (NHEK). Similarities exist between PKC and NHEK with respect to both TNF-alpha
      and IL-8 production. The expression profile of TNF-alpha in MSK3877 cells mimics
      that of NHEK. In contrast, the profile of IL-8 expression opposes that of PKC and
      NHEK. These results suggest that porcine keratinocytes are susceptible to jet
      fuel toxicity. However, the responses of immortalized cells may vary from those
      of PKC and NHEK necessitating cautious interpretation of such data.

PMID- 11246176
TI  - The anti-anginal drug fendiline increases intracellular Ca(2+) levels in MG63
      human osteosarcoma cells.
AB  - The effect of fendiline, an anti-anginal drug, on cytosolic free Ca(2+) levels
      ([Ca(2+)](i)) in MG63 human osteosarcoma cells was explored by using fura-2 as a
      Ca(2+) indicator. Fendiline at concentrations between 1 and 200 microM increased
      [Ca(2+)](i) in a concentration-dependent manner and the signal saturated at 100
      microM. The Ca(2+) signal was inhibited by 65+/-5% by Ca(2+) removal and by 38+/
      5% by 10 microM nifedipine, but was unchanged by 10 microM La(3+) or verapamil.
      In Ca(2+)-free medium, pre-treatment with 1 microM thapsigargin (an endoplasmic
      reticulum Ca(2+) pump inhibitor) to deplete the endoplasmic reticulum Ca(2+)
      store inhibited fendiline-induced intracellular Ca(2+) release. The Ca(2+)
      release induced by 50 microM fendiline appeared to be independent of IP(3)
      because the [Ca(2+)](i) increase was unaltered by inhibiting phospholipase C with
      2 microM U73122. Collectively, the results suggest that in MG63 cells fendiline
      caused an increase in [Ca(2+)](i) by inducing Ca(2+) influx and Ca(2+) release in
      an IP(3)-independent manner.

PMID- 11246177
TI  - Sex-dependent regulation by dexamethasone of murine hydroxysteroid
      sulfotransferase gene expression.
AB  - To determine whether glucocorticoid-inducible expression of hepatic
      hydroxysteroid sulfotransferase is conserved in mouse, the effects of
      dexamethasone (DEX) on hydroxysteroid sulfotransferase (mSULT2A) gene expression
      were investigated in primary cultured hepatocytes prepared from C57BL/6J mice. In
      female mouse hepatocytes, DEX (10(-7) and 10(-5) M, respectively) produced 8.2-
      and 17.8-fold increases, respectively, in the amounts of mSULT2A mRNA relative to
      control. By contrast, mSULT2A mRNA levels were undetectable in male mouse
      hepatocytes. Female-predominant mSULT2A mRNA expression was also observed in
      liver samples from C57BL/6J and three other mouse strains. Treatment of primary
      cultured female mouse hepatocytes with dihydrotestosterone in the presence of DEX
      suppressed mSULT2 expression. Transfection of primary cultured male or female
      mouse hepatocytes with a rat SULT2-40/41 reporter construct revealed that
      hepatocytes of both sexes have sufficient machinery to achieve DEX-inducible
      SULT2 transcription. However, treatment with the potent histone deacetylase
      inhibitor trichostatin A failed to elicit mSULT2A expression in male mouse
      hepatocytes.

PMID- 11246179
TI  - Effect of structured preoperative teaching on anxiety levels of patients
      scheduled for cataract surgery.
AB  - Cataract surgery is an outpatient, fast-paced surgical intervention that requires
      preoperative patient education to ensure success. The purpose of this study was
      to determine the effect of structured preoperative instructions on anxiety levels
      of patients scheduled for cataract surgery. A pretest/posttest classical
      experimental design was used to test the hypothesis. Anxiety was assessed by
      using the Spielberger State-Trait Anxiety Inventory. Blood pressure, pulse, and
      respiration were measured to assess the stimulation of the sympathetic nervous
      system in response to stress. The findings of this study support the hypothesis
      that structured preoperative instructions will decrease the anxiety level of
      patients scheduled for cataract surgery.

PMID- 11246180
TI  - Developing nursing leadership in an ambulatory surgical center through shared
      responsibility.
AB  - As health care continues to change at an unprecedented pace, so must nursing
      models of leadership. Nurse managers must look at successful models of leadership
      from the past and build successful components into new models of nursing health
      care leadership. The bureaucratic hierarchical system of the past does not keep
      today's nurse satisfied, nor are there monies in our current health care system
      for multiple layers of management. The leadership skills inherent in every
      professional staff nurse must be used and developed within the new health care
      arena for fiscal responsibility as well as professional satisfaction. Presented
      is one model used at our ambulatory surgical center. It is based on the premise
      of "shared responsibility" in which each person functions as a manager and a
      leader instead of one individual functioning to lead all who must be managed.
      Duties and responsibilities are divided among staff members, and each person has
      authority, responsibility, and accountability for specific tasks and functions
      with the ambulatory surgical center (ASC).

PMID- 11246181
TI  - Certification and competency: what's the connection?

PMID- 11246182
TI  - My involvement in ophthalmic nursing.

PMID- 11246183
TI  - Identifying pain in the hospice patient.

PMID- 11246185
TI  - The complexity of visual hallucinations.

PMID- 11246186
TI  - A paradigm shift in cataract surgery: less for the surgeon to do--more for the
      nurses and technicians to do.

PMID- 11246188
TI  - The KySS (Keep your children/yourself Safe and Secure) campaign: a national
      effort to reduce psychosocial morbidities in children and adolescents.

PMID- 11246191
TI  - Childhood obesity: taking on the issue.

PMID- 11246192
TI  - PNPs as catalysts in child care policymaking.
AB  - Dramatic socioeconomic changes in American family life, along with welfare
      reform, school readiness initiatives, and research on the relationship between
      child development and child care, have generated new interest in child care
      policy. Pediatric nurse practitioners and other pediatric nurses have much to
      contribute to the formulation of national, state, and local child care policies,
      especially if they are knowledgeable of key policies and regulatory issues. This
      article outlines these concepts with an eye toward promoting how pediatric nurses
      might reclaim their role as catalysts for promoting high-quality child care.

PMID- 11246193
TI  - Reshaping primary care: the Healthy Steps Initiative.
AB  - The Healthy Steps Initiative, funded by the Commonwealth Fund in New York and
      developed and implemented by Boston University School of Medicine, is an enhanced
      approach to pediatric care in the first 3 years of life. The goals of this effort
      in transforming pediatric care include (a) supporting the physical and emotional
      development of each infant and young child; (b) supporting a parental sense of
      confidence in their child-rearing knowledge and skills; and (c) supporting the
      clinical effectiveness of pediatric primary care practices to meet the needs of
      young children and families. The Healthy Steps Initiative enhances well-child
      care to achieve these goals by providing child development information and
      support as part of an expanded approach to pediatric primary care. Healthy Steps
      offers both pediatric practices and families a vehicle for meeting the needs of
      infants and young children within a preventative framework. This unique program,
      which is being quantitatively and qualitatively evaluated over 3 years, has been
      initiated in more than 24 pediatric sites nationwide.

PMID- 11246194
TI  - The precollege examination: fostering a healthy transition.
AB  - The college years are marked by major life changes, character development,
      decision making about the future, added responsibilities, and moving away from
      home. Nurse practitioners have the unique opportunity to facilitate this
      transition to adulthood by using the precollege examination to screen for
      potential problems and to encourage the development of responsible health
      promoting behaviors.

PMID- 11246195
TI  - Repeated sexual abuse allegations: a problem for primary care providers.
AB  - Sexual abuse of children is a problem of epidemic proportions in the United
      States. Primary care providers, including pediatric nurse practitioners, are
      increasingly presented with the problem of alleged sexual abuse in their
      patients, and primary care providers typically find it difficult to perform
      medical evaluations of children for sexual abuse. Having a child present
      repeatedly with sexual abuse concerns that cannot be substantiated is a stressful
      and frustrating experience for primary care providers. A case study is presented
      that illustrates the complexity and difficulty of one such case. A review of the
      literature will discuss the impact of divorce and Munchausen syndrome by proxy on
      repeated allegations of sexual abuse. Implications for practice are discussed,
      and a plan that addresses repeated sexual allegations in primary care settings is
      outlined.

PMID- 11246196
TI  - Amela's view of war-torn Sarajevo.

PMID- 11246197
TI  - Shaken baby syndrome.

PMID- 11246198
TI  - New anticonvulsants for use in pediatric patients (part I).

PMID- 11246199
TI  - Constipation and weakness.

PMID- 11246200
TI  - The grand finale.

PMID- 11246201
TI  - Making time for teaching.

PMID- 11246202
TI  - Practice identity, collaboration, and optimal access to effective health care.

PMID- 11246203
TI  - Macromolecular triplex zipping observed in derivatives of fungal (1 --> 3)-beta-D
      glucan by electron and atomic force microscopy.
AB  - Scleroglucan, a comb-like branched (1 --> 3)-beta-D-glucan, dissolves in water as
      a stiff, triple-helical structure with the single glucose branches extending from
      the surface. The aim of this study is to investigate structural changes in the
      triple-helical structure associated with selective chemical modification of the
      side chains. Electron and atomic force microscopy, respectively, were used to
      investigate the macromolecular structures of aldehyde and carboxylated
      derivatives of scleroglucan-namely, scleraldehyde and sclerox-with different
      degrees of substitution. Scleraldehyde was observed to have structures resembling
      the triplex of the unmodified scleroglucan for all degrees of substitution up to
      1.0. Additionally, an increasing tendency to aggregate for the higher degrees of
      substitution was observed. Fully carboxylated scleroglucan, sclerox(1.0),
      prepared from solutions at ionic strengths below 1.0M, revealed dispersed,
      flexible, coil-like structures. This indicates an electrostatic-driven strand
      separation of the scleroglucan triple-helical structure occurring concomitant
      with an increasing fraction of the side chains bearing carboxylate groups.
      Annealed sclerox(1.0) samples in aqueous 1.0 and 1.5M NaCl exhibited partly, or
      completely, reassociated triplex ensembles, with species ranging from apparently
      fully zipped linear and circular topologies, partly zipped structures with
      triplex strand separation occurring at the ends, to dispersed single-strands with
      random coil-like appearance. This study shows that periodate oxidation of the
      scleroglucan side chains is not a sufficient modification of the side chains to
      induce dissociation of the triple-helical structure, whereas further oxidation of
      the side chains to carboxylic groups dissociates the triple-helical structure
      when the degree of substitution is above 0.6.

PMID- 11246204
TI  - NMR conformational analysis of cis and trans proline isomers in the neutrophil
      chemoattractant, N-acetyl-proline-glycine-proline.
AB  - Alkaline hydrolysis of corneal proteins in the alkali-injured eye releases N
      acetyl-proline-glycine-proline (Ac-Pro-Gly-Pro-OH) among other peptides. It has
      been shown that this tripeptide is a neutrophil chemoattractant. Existing data
      suggest that the release of this peptide is the catalytic event for early
      neutrophil invasion of the cornea leading to corneal ulcers. In order to design
      inhibitors of this tripeptide chemoattractant that would block neutrophil
      invasion and diminish corneal ulcers, we studied the solution properties of this
      tripeptide by NMR spectroscopy and compared this peptide to Ac-Pro-Gly-OH (a
      weaker chemoattractant), and to Ac-Pro-OH (inactive). The NMR data were
      consistent with Ac-Pro-Gly-Pro-OH existing in solution as a mixture of four
      isomers with different cis and trans conformations about the two X-proline amide
      bonds. The isomer with two trans conformations (trans-trans) was the most
      dominant (41%) in aqueous solution. This was followed by the isomers with mixed
      cis and trans conformations (trans-cis, 26% and cis-trans, 20%). The isomer with
      two cis conformations (cis-cis) was the least favored (13%). The populations of
      these isomers were investigated in DMSO and they were similar to those reported
      in aqueous solutions except that the ordering of the trans-cis and cis-trans
      isomers were reversed. NMR NH temperature coefficients and nuclear Overhauser
      effect (NOE) measurements as well as CD spectroscopy were used to demonstrate
      that the four isomers exist primarily in an extended conformation with little
      hydrogen bonding. The available (NOE) information was used with molecular
      dynamics calculations to construct a dominant solution conformation for each
      isomer of the tripeptide. This information will serve as a model for the design
      of peptide and nonpeptide inhibitors of the chemoattractant.

PMID- 11246205
TI  - Sequence distribution and intercooperativity detection for two ligands
      simultaneously binding to DNA.
AB  - A method for detecting and quantifying the cooperativity in the simultaneous
      binding of two ligands, A and B, to DNA (intercooperativity; omega(AB)) is
      proposed. This involves the determination of an apparent affinity constant K(app)
      for one of the ligands (A) in the limit of its null saturation (nu(Alpha) --> 0),
      in the presence of the second one (B). A definition for this constant is given
      and an expression is derived corresponding to a simple model of competitive
      binding to an unbranched three-state homogeneous polar lattice with nearest
      neighbor interactions (Markov chain). The ratio between the apparent and
      intrinsic affinity constants of one ligand in the maximum saturation limit of the
      other one becomes omega(2)(AB), and thus can be graphically obtained from
      K(app)(A) vs nu(B) plots. All the frequencies that define the sequence
      distribution of ligands can be easily calculated by introducing some generalized
      statistical weights for the free lattice monomer in a standard sequence
      generating function procedure. A model of fluorescence quenching emission is
      obtained from such frequencies under the hypothesis of a short-range electron
      transfer mechanism of the deactivation; it confirms, as suggested by the binding
      model, an outstanding influence of the intercooperativity on the distribution.

PMID- 11246206
TI  - Scaled quantum mechanical force field for alanyl-alanine peptide in solution.
AB  - We have obtained ab initio scale factors and assigned frequencies for the alanine
      alanine peptide in water. Calculations were performed on the isolated acidic and
      basic Ala-Ala structures, two one-water basic Ala-Ala supermolecules, and one two
      water acidic and one two-water basic Ala-Ala supermolecules. Force constants were
      scaled using the experimentally determined Raman and Fourier transform infrared
      vibrational frequencies of four isotopic species of Ala-Ala in water at pH 13 and
      pH 1. Most of the 4-31G scale factors were transferable from smaller molecules.
      All but one scale factor were directly transferable between the pH 1 and pH 13
      species for coordinates unchanged by protonation in both the isolated and two
      water supermolecule structures. Scale factors for nonpolar coordinates were
      transferable between all Ala-Ala species with only a few small changes. Good
      agreement was obtained between the calculated and experimental frequencies for
      all isotopic species and structures.

PMID- 11246207
TI  - Quantitative analyses of anatomical and electrotonic structures of local spiking
      interneurons by three-dimensional morphometry in crayfish.
AB  - We quantitatively investigated the three-dimensional structure of the dendrites
      of local spiking interneurons using a confocal laser scanning microscope in the
      terminal abdominal ganglion of crayfish. We also studied their passive membrane
      properties electrophysiologically using the single-electrode current clamp
      techniques to analyze their electrotonic structure. All of the local spiking
      interneurons examined in this study lacked distinctive axonal structure and had a
      monopolar cell body that was connected with a fine primary process to a thick
      main segment. Numerous fine secondary processes projected from the main segment
      in the ganglionic neuropile. The average anatomical length of a secondary process
      from the main segment to its terminal was 261.9 +/- 15.2 microm. The average
      input resistance and membrane time constant of local spiking interneurons,
      obtained from their voltage responses to intracellular injection of step current
      pulses in the main segment, were 15.2 +/- 1.6 MOmega and 13.9 +/- 1.9 msec,
      respectively. Calculation of the electrotonic length of dendritic processes based
      on morphological and physiological data obtained in this study revealed that the
      average electrotonic length of secondary processes in local spiking interneurons
      was significantly longer than in local nonspiking interneurons, although both
      types of local interneurons showed apparently similar anaxonic structure. The
      steady-state voltage attenuation factors for the secondary processes of local
      spiking interneurons were significantly greater than those of local nonspiking
      interneurons in both centrifugal and centripetal directions. The larger
      electrotonic structure of local spiking interneurons compared to that of
      nonspiking interneurons appears to be compensated for by their excitable
      dendritic membrane.

PMID- 11246208
TI  - Brevican in the developing hippocampal fimbria: differential expression in
      myelinating oligodendrocytes and adult astrocytes suggests a dual role for
      brevican in central nervous system fiber tract development.
AB  - Brevican is one of the most abundant extracellular matrix proteoglycans in the
      mammalian brain. We have previously shown that brevican produced by gray matter
      astrocytes constitutes a major component of perineuronal extracellular matrix in
      the adult brain. In this paper, we investigate the expression of brevican in the
      postnatal hippocampal fimbria to explore the role of the proteoglycan in central
      nervous system fiber tract development. We demonstrate that brevican is expressed
      by both oligodendrocytes and white matter astrocytes in the fimbria, but the
      expression of brevican in these two glial cell types is differently regulated
      during development. At P14, brevican immunoreactivity was observed throughout the
      fimbria, with particularly strong immunoreactivity in the developing
      interfascicular glial rows. In situ hybridization showed that oligodendrocytes in
      the glial rows strongly express brevican during the second and third postnatal
      weeks. Expression in oligodendrocytes was then down-regulated after P21. In the
      adult fimbria, no brevican expression was observed in oligodendrocytes. The time
      window of brevican expression coincides with the phase in which immature
      oligodendrocytes actively extend membrane processes and enwrap axon fibers. In
      contrast, the expression in astrocytes started around P21 as oligodendrocytes
      began to down-regulate the expression. In the adult fimbria, brevican expression
      was restricted to astrocytes. In situ hybridization with isoform-specific probes
      and RNase protection assays showed that the authentic, secreted form of brevican,
      not the glycosylphosphatidylinositol-anchored variant, is the predominant species
      expressed in the developing fimbria. Our results suggest that brevican plays a
      dual role in developing and adult fiber tracts.

PMID- 11246209
TI  - Characterization of neuropeptide Y-expressing cells in the mouse retina using
      immunohistochemical and transgenic techniques.
AB  - The amacrine cells of the retina are a complex family of interneurons. They are
      made up of numerous subgroups, each with different morphologic and/or biochemical
      properties and each presumably serving a different function. In this study, we
      characterized one subgroup, defined by its expression of a peptide, neuropeptide
      Y (NPY). The cells were identified using antibodies to NPY and characterized
      using a transgenic mouse line that expressed the reporter enzyme, beta
      galactosidase, in the NPY-immunoreactive (NPY-IR) cells. We found that NPY-IR
      cells were present in two layers, the inner nuclear layer (INL) and the ganglion
      cell layer (GCL). The cells in both layers were densely distributed, with those
      in the INL having a mean density of 1452 +/- 65 cells/mm(2), and those in the GCL
      having a mean density of 644 +/- 41 cells/mm(2). The cells in the INL extended
      their processes in the sublamina of the inner plexiform layer (IPL) closest to
      the INL/IPL border, the presumptive OFF sublamina, and the cells in the GCL
      extended their processes in the sublamina near the GCL/IPL border, the
      presumptive ON sublamina. Both populations of cells were immunoreactive to a GABA
      transporter and, thus, likely GABAergic. The high density of these cells suggests
      that they play a prominent role in IPL processing. The location of their
      processes suggests that one population acts in the pathway that mediates OFF
      responses, and the other in the pathway that mediates ON responses, and their
      expression of a GABA marker indicates that their actions are likely inhibitory.

PMID- 11246210
TI  - Orbitomedial prefrontal cortical projections to hypothalamus in the rat.
AB  - A previous study in the rat revealed that distinct orbital and medial prefrontal
      cortical (OMPFC) areas projected to specific columns of the midbrain
      periaqueductal gray region (PAG). This study used anterograde tracing techniques
      to define projections to the hypothalamus arising from the same OMPFC regions. In
      addition, injections of anterograde and retrograde tracers were made into
      different PAG columns to examine connections between hypothalamic regions and PAG
      columns projected upon by the same OMPFC regions. The most extensive patterns of
      hypothalamic termination were seen after injection of anterograde tracer in
      prelimbic and infralimbic (PL/IL) and the ventral and medial orbital (VO/MO)
      cortices. Projections from rostral PL/IL and VO/MO targeted the rostrocaudal
      extent of the lateral hypothalamus, as well as lateral perifornical, and dorsal
      and posterior hypothalamic areas. Projections arising from caudal PL/IL
      terminated within the dorsal hypothalamus, including the dorsomedial nucleus and
      dorsal and posterior hypothalamic areas. There were also projections to medial
      perifornical and lateral hypothalamic areas. In contrast, it was found that
      anterior cingulate (AC), dorsolateral orbital (DLO), and agranular insular (AId)
      cortices projected to distinct and restricted hypothalamic regions. Projections
      arising from AC terminated within dorsal and posterior hypothalamic areas,
      whereas DLO and AId projected to the lateral hypothalamus. The same OMPFC regions
      also projected indirectly, by means of specific PAG columns, to many of the same
      hypothalamic fields. In the context of our previous findings, these data indicate
      that, in both rat and macaque, parallel but distinct circuits interconnect OMPFC
      areas with specific hypothalamic regions, as well as PAG columns.

PMID- 11246211
TI  - Influence of sex and estrus cycle on the sexual dimorphisms of the hypothalamic
      ventromedial nucleus: stereological evaluation and Golgi study.
AB  - Neurons in the ventromedial nucleus of the hypothalamus (VMN) display structural
      and biochemical sex differences in response to estrogen. Despite this fact,
      reports on sex differences in the morphology of the VMN are restricted to its
      volume and synaptic patterning. The aim of this study was to characterize the
      neuroanatomical sexual dimorphisms in the VMN and to investigate whether
      endogenous changes in ovarian steroid secretion influence such dimorphisms. The
      VMN of adult male rats and intact, aged-matched female rats killed on proestrus
      and diestrus day 1 was examined by using stereological methods applied to
      conventionally stained sections and Golgi-impregnated material. The VMN contained
      55,000 neurons in rats of both sexes, but its volume was, on average, 1.25 times
      larger in males than in females. The volume was greater in proestrus than in
      diestrus rats due to parallel changes in the neuronal somatic size. Unlike the
      dorsomedial division, neurons in the ventrolateral division had longer dendritic
      trees in proestrus than in diestrus females and males. The spine density was
      consistently higher in females than in males in both VMN divisions. In addition,
      in the ventrolateral part the magnitude of the sex differences varied across the
      estrus cycle, and reached the greatest value when females were in proestrus. The
      volume of the neuropil was significantly larger in males than in females, and was
      not affected by the estrus phase. Our results reveal that the magnitude of the
      neuroanatomical sex differences in the VMN vary across the estrus cycle due to
      the trophic influence of estrogen upon its neurons. They also show that the
      fundamental sex difference in the structure of the VMN is accounted for by the
      neuropil components.

PMID- 11246212
TI  - Functional organization of the suprachiasmatic nucleus of Xenopus laevis in
      relation to background adaptation.
AB  - The process of background adaptation in the toad Xenopus laevis is controlled by
      neurons in the suprachiasmatic nucleus (SC) that inhibit the release of alpha
      melanophore-stimulating hormone from the neuroendocrine melanotrope cells in the
      pituitary gland. We have identified the structural and functional organization of
      different neuropeptide Y (NPY)-containing cell groups in the Xenopus SC in
      relation to background adaptation. A ventrolateral, a dorsomedial, and a caudal
      group were distinguished, differing in location as well as in number, size, and
      shape of their cells. They also show different degrees of NPY immunoreactivity in
      response to different background adaptation conditions. In situ hybridization
      using a Xenopus mRNA probe for the exocytosis protein DOC2 revealed that
      melanotrope cells of black-adapted animals have a much higher expression of DOC2
      mRNA than white-adapted ones. This establishes that the degree of DOC2-mRNA
      expression is a good parameter to measure cellular secretory activity in Xenopus.
      We show that in the ventrolateral SC group, more NPY-positive neurons express
      DOC2-mRNA in white- than in black-adapted animals. In contrast, NPY-positive
      neurons in the dorsomedial group have a high secretory activity under the black
      adaptation condition. We propose that in black-adapted animals, NPY-positive
      neurons in the ventrolateral group, known to inhibit the melanotrope cells in
      white-adapted animals synaptically, are inhibited by NPY-containing interneurons
      in the dorsmedial group. NPY-positive neurons in the caudal group have similar
      secretory dynamics as the dorsomedial NPY neurons, indicating that they also play
      a role in background adaptation, distinct from that exerted by the ventrolateral
      and dorsomedial group.

PMID- 11246213
TI  - Olfactory protocerebral pathways processing sex pheromone and plant odor
      information in the male moth Agrotis segetum.
AB  - We investigated protocerebral processing of behaviorally relevant signals in the
      turnip moth, Agrotis segetum. Single neurons were studied both physiologically
      and morphologically using intracellular recording techniques. In moth pheromone
      communication systems, the presence of the complete, female-produced pheromone
      blend is necessary for male attraction. We predicted that more protocerebral
      neurons, compared with AL, would display blend interactions. However, only a few
      protocerebral neurons responded differently to the blend than could be deduced
      from the response to single components. The majority of the pheromone-sensitive
      protocerebral neurons identified in this study responded to the major pheromone
      component. In coding time, most AL neurons can follow a 5-Hz odor stimulus,
      whereas most protocerebral neurons failed at higher frequencies than 1 Hz. The
      majority of neurons that responded to the odorants tested innervated one or both
      of the protocerebral lateral accessory lobes. If only one of these was
      innervated, then the innervation always displayed a varicose appearance,
      suggesting a presynaptic function. Thus, information seems to be transferred from
      other protocerebral areas to the lateral accessory lobes. Into these, descending
      neurons sent smooth, postsynaptic branches. A majority of the neurons innervating
      the superior medial protocerebrum were found to display single-component
      specificity. Few additional correlations between odor specificity and structural
      characteristics were apparent.

PMID- 11246214
TI  - Subcellular distribution of 5-HT(1B) and 5-HT(7) receptors in the mouse
      suprachiasmatic nucleus.
AB  - The suprachiasmatic nucleus (SCN), a circadian oscillator, receives glutamatergic
      afferents from the retina and serotonergic (5-HT) afferents from the median
      raphe. 5-HT(1B) and 5-HT(7) receptor agonists inhibit the effects of light on SCN
      circadian activity. Electron microscopic (EM) immunocytochemical procedures were
      used to determine the subcellular localization of 5-HT(1B) and 5-HT(7) receptors
      in the SCN. 5-HT(1B) receptor immunostaining was associated with the plasma
      membrane of thin unmyelinated axons, preterminal axons, and terminals of optic
      and nonoptic origin. 5-HT(1B) receptor immunostaining in terminals was almost
      never observed at the synaptic active zone. To a much lesser extent, 5-HT(1B)
      immunoreaction product was noted in dendrites and somata of SCN neurons. 5-HT(7)
      receptor immunoreactivity in gamma-aminobutyric acid (GABA), vasoactive
      intestinal polypeptide (VIP), and vasopressin (VP) neuronal elements in the SCN
      was examined by using double-label procedures. 5-HT(7) receptor immunoreaction
      product was often observed in GABA-, VIP-, and VP-immunoreactive dendrites as
      postsynaptic receptors and in axonal terminals as presynaptic receptors. 5-HT(7)
      receptor immunoreactivity in terminals and dendrites was often associated with
      the plasma membrane but very seldom at the active zone. In GABA-, VIP-, and VP
      immunoreactive perikarya, 5-HT(7) receptor immunoreaction product was distributed
      throughout the cytoplasm often in association with the endoplasmic reticulum and
      the Golgi complex. The distribution of 5-HT(1B) receptors in presynaptic afferent
      terminals and postsynaptic SCN processes, as well as the distribution of 5-HT(7)
      receptors in both pre- and postsynaptic GABA, VIP, and VP SCN processes, suggests
      that serotonin plays a significant role in the regulation of circadian rhythms by
      modulating SCN synaptic activity.

PMID- 11246215
TI  - Chemical organization of the macaque monkey olfactory bulb: II. Calretinin,
      calbindin D-28k, parvalbumin, and neurocalcin immunoreactivity.
AB  - The distribution and morphologic features of calcium-binding protein- (calbindin
      D-28k, calretinin, neurocalcin, and parvalbumin) immunoreactive elements were
      studied in the macaque monkey olfactory bulb by using specific antibodies and the
      avidin-biotin-immunoperoxidase method. A characteristic laminar pattern of
      stained elements was observed for each marker. Scarce superficial short-axon
      cells and superficial stellate cells demonstrated calbindin D-28k
      immunoreactivity in the outer layers, whereas a moderate number of calbindin D
      28k-immunoreactive granule cells and scarce deep short-axon cells were observed
      in the inner layers. Calretinin-staining demonstrated abundant periglomerular
      cells and granule cells and a scarce number of other interneuronal populations.
      Most neurocalcin-immunopositive elements were external and medial tufted cells
      and periglomerular cells, although other scarcer interneuronal populations were
      also immunostained. A few superficial and deep short-axon cells as well as small
      interneurons in the external plexiform layer were the only elements
      immunoreactive to parvalbumin. The distribution of the immunoreactive elements in
      the olfactory bulb of the macaque monkey showed a high similarity to that
      reported in the human, whereas it demonstrated a different and simpler pattern to
      what has been reported in the olfactory bulb of macrosmatic animals. It suggests
      more homogeneous calcium-mediated cell responses after stimulation that could be
      correlated to the lower capability to modulate olfactory signals in microsmatic
      animals. In addition, these results indicate that experimental models in rodents
      do not provide an accurate estimation of calcium-binding protein-immunoreactive
      neuronal populations in the primate olfactory system.

PMID- 11246217
TI  - Genetic and environmental interactions on oral cancer in Southern Thailand.
AB  - Many countries are interested in understanding the relationship between genetic
      susceptibility and their prevalent environmental cancers for disease prevention.
      In Thailand we conducted a population-based case-control study of 53 matched
      pairs to assess the risk of oral cancer in relation to genetic polymorphism of
      the glutathione-S-transferase genes (GSTM1 and GSTT1) in cigarette smokers,
      alcohol drinkers, and betel quid chewers. Interaction of the genes with other
      potential risk factors such as local bean consumption were also elucidated.
      Homozygous deletion of GSTM1 has a frequency of 56.6% (n = 30 over 53) among the
      patients and 30.2% (16/53) among the controls. This gene is associated with a 2.6
      fold higher risk for development of oral cancer (95% CI 1.04-6.5). Among the null
      GSTM1 individuals, those who smoke, consume alcohol, and/or chew betel quid have
      a significantly increased risk for oral cancer with an odd ratio (OR) = 4.0 (95%
      CI = 1.2-13.7), OR = 7.2 (95% CI = 1.5-33.8), and OR = 4.4 (95% CI = 1.1-17.8),
      respectively. Interactions between any two of the lifestyle habits for oral
      cancer risk, however, are not found. The frequency of the GSTT1 null genotype is
      34.0% (18/53) among the patients and 47.2% (25/53) among our controls. There is
      no association between the GSTT1 null allele and oral cancer risk. In conclusion,
      our study provides data to indicate that individuals who have homozygous deletion
      of the GSTM1 gene have increased risk for oral cancer. The risk increases further
      when these individuals are exposed to environmental toxicants such as chemicals
      in cigarette smoke, alcohol, and betel quid. These baseline data can be applied
      to a larger population-based study, both to verify the observation and to conduct
      mechanistic investigations.

PMID- 11246216
TI  - Evaluation of the rodent micronucleus assay by a 28-day treatment protocol:
      Summary of the 13th Collaborative Study by the Collaborative Study Group for the
      Micronucleus Test (CSGMT)/Environmental Mutagen Society of Japan (JEMS)-Mammalian
      Mutagenicity Study Group (MMS).
AB  - To examine whether micronucleus tests can be incorporated into general toxicology
      assays, we performed micronucleus tests applying the treatment protocols
      typically used in such assays. In this 13th Collaborative Study of the CSGMT,
      both rats and mice were tested, although rats were used in the majority of the
      studies. Fifteen mutagens were tested in rats, mainly by oral (p.o.)
      administration. Micronucleus induction was evaluated 2, 3, and 4 days, and 1, 2,
      3, and 28 days after the beginning of the treatment in the peripheral blood, and
      at 28 days in the bone marrow. Of the 15 chemicals that induced micronuclei in
      rats in short-term assays, two chemicals (1,2-dimethylhydrazine.2HCl and
      mitomycin C) were negative in all our experiments, possibly because of
      insufficient dose levels. The remaining 13 were positive within the estimated
      dose range of a general toxicology assay, suggesting the possibility of
      integrating the micronucleus assay into general toxicology assays. Three patterns
      were observed in micronucleus induction during the period of repeated treatment:
      (1) gradual increases in micronucleus frequency with sequential doses, (2) a peak
      at 3-5 days followed by gradual decreases in micronucleus frequency with
      sequential doses, and (3) a rapid increase in micronucleus frequency followed by
      a plateau. We evaluated factors that might have been involved in those patterns,
      such as the spleen function, target organ exposure, extramedullary hematopoiesis,
      hypothermia, and hypoxia. Another factor we considered was dosage. Because the
      dosages employed in a general toxicity assay are usually lower than those used in
      short-term micronucleus assays, this discrepancy was considered the greatest
      potential problem for integrating the micronucleus assay into general toxicology
      assays. Our results indicate that the integration of the micronucleus assay into
      a 28-day toxicological assay is feasible. To serve this purpose, blood samples
      collected 4 days after the beginning of treatment and blood and bone marrow
      samples collected at autopsy should be examined. Furthermore, although it is
      recognized that mice may be suitable for performing independent micronucleus
      assays, we propose that rats can provide biologically important and relevant
      information regarding potential chemical mutagens that can be evaluated under
      conditions used in the conduct of general toxicology studies.

PMID- 11246218
TI  - Structure-activity analysis of the potentiation by aminothiols of the chromosome
      damaging effect of bleomycin in G0 human lymphocytes.
AB  - The radioprotective aminothiols 2-[(aminopropyl)amino] ethanethiol (WR-1065) and
      cysteamine (CSM) potentiate the induction of chromosomal damage by the
      radiomimetic compound bleomycin (BLM) in G0 human lymphocytes. To investigate the
      mechanism of potentiation, we measured the clastogenic activity of BLM in the
      cytokinesis-block micronucleus assay in the presence and absence of amines,
      thiols, and aminothiols. The hydroxy analog of WR-1065, 2-(3-aminopropylamino)
      ethanol (WR-OH), potentiates BLM only slightly, indicating the critical nature of
      the thiol group. As thiols, WR-1065 and CSM may donate electrons for the
      activation of Fe(+2)-BLM or for the regeneration of Fe(+2)-BLM from inactive
      Fe(+3)-BLM. The amines putrescine, spermidine, and spermine all potentiate BLM,
      but they are weaker potentiators than the aminothiols, and they are effective
      only at high concentrations. Their activity, like that of WR-OH, is probably a
      consequence of conformational alteration of DNA. Dithioerythritol (DTE) and 2
      mercaptoethanol (2-ME), thiols lacking an amino group, are less effective
      potentiators of BLM than are the aminothiols. The thiol group of WR-1065 and CSM
      is therefore essential, but insufficient, for explaining the strong enhancement
      of BLM activity. The cationic nature of CSM and WR-1065, conferred by the amino
      groups, evidently concentrates the active thiol function at the site of BLM
      action on DNA. As expected on this basis, the diamine WR-1065 is a more effective
      potentiator of BLM than is the monoamine CSM, whereas cysteine and N
      acetylcysteine (NAC), which lack a net positive charge, potentiate BLM only
      weakly. These studies suggest that potentiation of the clastogenic action of BLM
      by aminothiols can be explained by the combination of a thiol-mediated redox
      mechanism and an amine-mediated targeting of the thiol function to DNA.

PMID- 11246219
TI  - Expression of ATM in ataxia telangiectasia fibroblasts rescues defects in DNA
      double-strand break repair in nuclear extracts.
AB  - Ataxia telangiectasia (A-T) is a human genetic disorder characterized by
      progressive cerebellar degeneration, hypersensitivity to ionizing radiation (IR),
      immunodeficiency, and high cancer risk. At the cellular level, IR sensitivity and
      increased frequency of spontaneous and IR-induced chromosomal breakage and
      rearrangements are the hallmarks of A-T. The ATM gene, mutated in this syndrome,
      has been cloned and codes for a protein sharing homology with DNA-PKcs, a protein
      kinase involved in DNA double-strand break (DSB) repair and DNA damage responses.
      The characteristics of the A-T cellular phenotypes and ATM gene suggest that ATM
      may play a role similar to that of DNA-PKcs in DSB repair and that there is a
      primary DNA repair defect in A-T cells. In the current study, the function of ATM
      in DNA DSB repair was evaluated in an in vitro system using two plasmids,
      carrying either an EcoRI-induced DSB within the lacZalpha gene or various
      endonuclease-induced DSB in the SupF suppressor tRNA gene. We found that the DSB
      repair efficiency in A-T nuclear extracts was comparable to, if not higher than,
      that in normal nuclear extracts. However, the repair fidelity in A-T nuclear
      extracts was decreased when repairing DSB with short 5' and 3' overhangs (<4 base
      pairs (bp)) or blunt ends, but not 5' 4-bp overhangs. Sequencing of the mutant
      plasmids revealed that deletions involving 1-6 nucleotide microhomologies were
      the major class of mutations in both A-T and normal extracts. However, the size
      of the deletions in plasmids from A-T nuclear extracts was larger than that from
      normal nuclear extracts. Expression of the ATM protein in A-T cells corrected the
      defect in DSB repair in A-T nuclear extracts. These results suggest that ATM
      plays a role in maintaining genomic stability by preventing the repair of DSB
      from an error-prone pathway.

PMID- 11246220
TI  - Spontaneous mutation of the lacI transgene in rodents: absence of species,
      strain, and insertion-site influence.
AB  - Comparison of spontaneous mutation spectra derived from different transgenic
      constructs can provide valuable insights for interpreting the mechanisms of
      spontaneous mutation. In this study, spontaneous mutation frequencies and spectra
      of the lacI transgene are compared in the liver of C57BL/6, B6C3F1, and BC-1 mice
      and F344 rats. Before correction for clonal expansion, the mutant frequency
      varied from 2.6 +/- 0.45 to 5.0 +/- 2.4 x 10(-5). Correction for potential clonal
      expansion reduced the range in mutation frequency to between 2.3 +/- 0.45 and 3.5
      +/- 2.0 x 10(-5). There is thus no statistical difference in spontaneous mutation
      frequency between the different strains and species. G:C --> A:T transitions and
      to a lesser extent, G:C --> T:A transversions dominate the mutational spectra in
      all of these animals. In three strains of mice, G:C --> A:T transitions account
      for 50.7-53.3% of mutation, 81.7-83.8% of which involve CpG sites, whereas G:C -
      > T:A transversions account for 17.8-32.9% of mutations with 43.2-50.0% found at
      CpG sites. In rats, G:C --> A:T transitions account for 38.0% of the spectra,
      70.0% of which involve CpG sites, whereas G:C --> T:A transversions account for
      23.0% of the spectra, 70.0% of which involve CpG sites. The distribution of other
      classes of mutations is also very similar. We conclude that, despite reports
      about species and strain differences in induced mutation, spontaneous mutations
      in the lacI transgene appear to be similar, regardless of genomic location,
      rodent strain, or species. In addition to insights into spontaneous mutation,
      this study also provides essential data for comparison with and interpretation of
      induced mutations.

PMID- 11246221
TI  - Quantitative plasmid mixture analysis using the fluorogenic 5'-nuclease
      polymerase chain reaction assay.
AB  - The fluorogenic 5'-nuclease polymerase chain reaction (PCR) assay has been shown
      to be useful for quantifying a given DNA target in a sample. Here we show how an
      existing PCR protocol can be amended for quantification by incorporating
      distinctive dual-labeled, sequence-specific oligonucleotide probes and resulting
      in a two- to threefold broader and more reliable dynamic range than that of
      conventional end-point analysis of PCR products. Moreover, we show a multiplex
      situation in which two targets, one normal and one mutated, can be amplified and
      quantified simultaneously and in the same reaction tube. Use of this novel
      approach for quantitative PCR applications eliminates the need for post-PCR
      processing and has clinical- and research-based diagnostic applications,
      particularly for measuring levels of mutations in a mixture.

PMID- 11246222
TI  - Genotoxic effects of carbon black particles, diesel exhaust particles, and urban
      air particulates and their extracts on a human alveolar epithelial cell line
      (A549) and a human monocytic cell line (THP-1).
AB  - The possible genotoxicity of small particulate matter has been under
      investigation for the last 10 years. Diesel exhaust particles (DEP) are
      considered as "probably carcinogenic" (IARC group 2A) and a number of studies
      show genotoxic effects of urban particulate matter (UPM). Carbon black (CB) is
      carcinogenic in rats. In this study the cytotoxic and genotoxic potency of these
      three particle types was investigated by exposing human cells (A549 and THP-1
      cell lines) in vitro to CB, DEP (SRM 1650, NIST), and UPM (SRM 1648, NIST) for 48
      hr. Cytotoxicity was assessed using the Alamar Blue assay, whereas genotoxicity
      was assessed using the single-cell gel electrophoresis (comet assay). The
      particles were characterized with regard to their mean diameter in tissue culture
      medium (CB 100 nm, DEP 400 nm, UPM 2 microm), their total carbon content (CB 99%,
      DEP 85%, UPM 15%), and their acid-soluble metal composition (UPM >> CB
      approximately DEP). The concentrations ranged from 16 ng/ml to 16 microg/ml for
      cytotoxicity tests and from 16 ng/ml to 1.6 microg/ml for genotoxicity tests. In
      both assays, paraquat was used as a reference chemical. The CB, DEP, and UPM
      particles showed no significant cytotoxicity. However, all three particles were
      able to cause significant DNA damage, although to a different extent in the two
      cell lines. The genotoxicity of washed particles and dichloromethane extracts was
      also investigated. In THP-1 cells CB washed particles and DEP extracts caused
      significant DNA damage. This difference in effect may be related to differences
      in size, structure, and composition of the particles. These results suggest that
      CB, DEP, and UPM are able to cause DNA damage and, therefore, may contribute to
      the causation of lung cancer. More detailed studies on influence of size,
      structure, and composition of the particles are needed.

PMID- 11246223
TI  - Pentachlorophenol potentiates benzo[a]pyrene DNA adduct formation in adult but
      not infant B6C3F1 male mice.
AB  - The objective of this study is to determine whether pentachlorophenol (PCP)
      alters benzo[a]pyrene (B[a]P)-induced DNA adduct formation in infant and adult
      B6C3F1 male mice. Mice were exposed intraperitoneally to 55 microg B[a]P/g body
      weight (BW) alone and in combination with several doses of PCP in DMSO. The 32P
      postlabeling assay was used to analyze for (+/-) anti-7,8-diol-9,10-epoxide-B[a]P
      N(2)deoxyguanosine (BPDE-N(2)G) adducts formed in liver and lung DNA. Hepatic DNA
      also was analyzed for 8-hydroxy-2'-deoxyguanosine (8-OHdG) base damage in mice
      exposed to PCP. 8-OHdG was not detected at any dose of PCP in infant or adult
      mice. PCP exhibited an antagonistic effect on BPDE-N(2)G accumulation in infant
      mice exposed to B[a]P in combination with 50 microg PCP/g BW at both 12 and 24
      hr. Comparatively, BPDE-N(2)G adducts were increased in adult mice exposed to
      binary mixtures at 24 hr in both hepatic and lung DNA (P < 0.05). Multiple
      comparison analysis between infant and adult mice revealed that adduct levels in
      infants exposed to B[a]P alone or in combination with PCP were not different from
      those observed in adult mice exposed to B[a]P. However, a significant increase in
      adducts was observed in adult mice exposed to a combination of B[a]P and PCP
      compared to that in all other treatment groups (P < 0.05). These results suggest
      that PCP alters the metabolism of B[a]P in both infant and adult mice through
      different mechanisms, and that infants are not susceptible to the potentiating
      effects of PCP observed in adult mice.

PMID- 11246224
TI  - Variation of micronucleated erythrocytes in peripheral blood of Sciurus
      aureogaster in relation to age: an increment of micronucleated polychromatic
      erythrocytes after the administration of colchicine.
AB  - In some species, in which the human is included, the influence of age in the
      variation in the number of micronucleated erythrocytes (MNE) is known. In the
      present work we show how the process of aging influences the number of
      spontaneous MNE in the gray squirrel (Sciurus aureogaster). Because of the
      difficulty of knowing the age of each animal, 69 animals were weighed at their
      arrival to the laboratory and at the start of sample taking, with the supposition
      that the heaviest animals were the oldest and those with the lightest weight were
      the youngest. The major number of MNE was found in the younger animals, whereas
      the adults displayed less MNE (P < 0.0001). A group of 11 animals were sampled
      every 15 days over a period of 6 months, and the number of MNE were found to
      decrease with an increment in the weight in conformity with the time elapsed.
      These results showed that in the gray squirrel, the number of spontaneous MNE in
      peripheral blood depend on age. An additional interesting datum about the
      increment of MNE after the administration of colchicine is shown.

PMID- 11246225
TI  - Thyrotropin-releasing hormone and its receptor in glia.
AB  - The presence of thyrotropin-releasing hormone (Thyroliberin, TRH) and its
      receptor (TRH-R) in frozen coronal sections of the adult rat spinal cord and
      neonatal rat astroglial cultures was investigated by means of immunocytochemistry
      and Western blot using polyclonal antibodies generated against the hormone and
      monoclonal antibodies originated against discrete sequences of the type 1 rat TRH
      receptor (TRH-R1). TRH-R1 and TRH are present both in astroglial cells from adult
      rats and in cultured cells from newborn animals. The localization of TRH and TRH
      R1 in nonneuronal cells in the central nervous system may reflect that some of
      the neurotrophic actions of TRH upon the central nervous system are mediated by
      glial cells.

PMID- 11246226
TI  - Differential microglial response to progressive neurodegeneration in the murine
      mutant Wobbler.
AB  - Activated microglia is associated with neurodegenerative processes, but the
      precise role of this cell population is difficult to identify. Most experimental
      models employed to examine microglial responses involve acute alterations of
      neuronal integrity, in contrast to the progressive nature of neurodegenerative
      diseases. In order to approach the clinical situation better, the microglial
      response was analyzed in the murine mutant Wobbler, which exhibits a well
      characterized neurodegenerative pathology, manifested by motoneuronal death
      following a period of cellular dysfunction with characteristic morphological
      features. Microglial cells were identified using anti-Mac1 or anti-IgG
      antibodies. Examination of the changes in density, localization, and phenotype of
      microglia differentiated two types of responses in Wobblers. A first type of
      response was observed as early as in the third week after birth, when the only
      apparent neuronal defect was the morphological alteration of a subset of
      motoneurons in the cervical spinal cord, which was maintained later on. The
      activated microglia extended long processes that selectively ensheathed
      vacuolated motoneurons. At later stages, when motoneuron death became prominent,
      an additional type of response was characterized by an increased density of
      reactive microglia that was seen extending throughout the cervical enlargement.
      This secondary microglial response occurred in parallel to the infiltration of T
      lymphocytes. Thus, these results point to a differential response of microglial
      cells to a progressive neurodegenerative process.

PMID- 11246227
TI  - Protein kinase C mediates neurite guidance at an astrocyte boundary.
AB  - During development, astrocytes play an active role in directing axons to their
      final targets. This guidance has been attributed in part to the increased
      expression of guidance molecules, such as tenascin-C and chondroitin sulfate
      proteoglycans, by boundary-forming astrocytes. We have previously used a culture
      model of astrocyte boundaries to demonstrate that neurites growing on permissive
      astrocytes alter their trajectory as they encounter less-permissive astrocytes.
      The present study investigated the role of the protein kinase C (PKC) family of
      signal transduction molecules in this form of axonal guidance. Neurons were
      plated onto mixed astrocyte monolayers in the presence of agents that either
      downregulate the phorbol ester-sensitive PKC isoforms or inhibit PKC. Both
      downregulation and inhibition of PKC increased the percentage of neurons that
      crossed onto the nonpermissive astrocytes. On astrocyte monolayers, phorbol ester
      modulation of PKC but not PKC inhibitors resulted in a decrease in overall
      neurite extension. PKC inhibitors also caused a similar alteration in the
      neuronal response to cell-free boundaries, at concentrations that did not inhibit
      neurite extension. Thus, phorbol-ester-sensitive PKC isoforms direct the guidance
      of neurites by astrocyte-derived matrix molecules.

PMID- 11246228
TI  - Synthesis and processing of apolipoprotein E in human brain cultures.
AB  - Apolipoprotein E (apoE) plays a role in the distribution of lipid within many
      organs and cell types in the human body, including neurons and astrocytes of the
      central nervous system (CNS). The apoE4 isoform is also a genetic risk factor for
      late onset Alzheimer's disease (AD). However, the mechanism by which apoE is
      involved in AD is largely unknown. In order to understand how apoE is involved in
      the distribution of lipid in the CNS, we sought to investigate not only the
      origin of intraneuronal apoE, but the pathway by which it is processed once
      synthesized. We have established that human neurons can synthesize apoE in the
      presence of astrocytes, and that intracellular neuronal apoE is processed through
      the rough endoplasmic reticulum, golgi, and CD63-positive lysosomes where it may
      be stored before secretion. Our results also suggest that apoE synthesis is
      regulated by a feedback mechanism, controlled by the neuron itself. This
      regulatory mechanism may be essential to the maintenance of neuronal cholesterol
      concentrations and in turn membrane stability.

PMID- 11246229
TI  - Neuronal nicotinic acetylcholine receptor expression by O2A/oligodendrocyte
      progenitor cells.
AB  - Oligodendrocyte precursor cells (O2A/OPC, A2B5(+)) were examined for expression
      of neuronal nicotinic acetylcholine receptors (nAChR). RT-PCR analysis and
      immunocytochemistry of O2A/OPCs purified from the rat corpus collusum revealed
      the expression of nAChR subunits alpha3, alpha4, alpha5, alpha7, beta2, and
      beta4. Immunoreactivity toward nAChR subunits was not detected in cells induced
      to differentiate into either oligodendrocytes or astrocytes. Approximately 65% of
      O2A/OPCs loaded with the calcium-responsive dye FURA-2 increased their
      intracellular free calcium in response to nicotine application. This response was
      sensitive to the nAChRalpha4/beta2 antagonist, dihydro-beta-erythroidine
      (DHbetaE), and the voltage-gated calcium channel antagonist, nifedipine. A subset
      of nicotine-responsive cells (37%) established DHbetaE or nifedipine-sensitive
      intracellular free calcium oscillations that continued in the presence of
      nicotine. Typical oscillations occurred at intervals of 20 to 30 s with
      progressively diminished amplitudes over a period of 2 to 3 min. In rare cases,
      oscillations persisted for as long as 10 min. O2A/OPCs exposed to carbachol or
      AMPA produced no oscillations despite robust increases in intracellular free
      calcium. The expression of nAChRs in non-neuronal glial precursor cells suggests
      an expanded role for this receptor system in the development of the mammalian
      brain. GLIA 33:306-313, 2001. Published 2001 Wiley-Liss, Inc.

PMID- 11246230
TI  - Neurofibromatosis 1 (NF1) heterozygosity results in a cell-autonomous growth
      advantage for astrocytes.
AB  - Individuals with neurofibromatosis 1 (NF1) develop low-grade astrocytomas at an
      increased frequency. To gain insight into the function of the Nf1 gene product as
      a growth regulator for astrocytes, we examined mice heterozygous for a targeted
      Nf1 mutation. In our previous studies, we demonstrated increased numbers of
      proliferating astrocytes in Nf1 heterozygote (Nf1+/-) mice in vivo. We now show
      that cultured Nf1+/- astrocytes exhibit a cell-autonomous growth advantage in
      vitro associated with increased p21-ras pathway activation. Furthermore, we
      demonstrate that Nf1+/-;wild-type N-ras mice have a similar astrocyte growth
      advantage in vitro and in vivo as either oncogenic N-ras or Nf1+/-; oncogenic N
      ras mice. Lastly, mice heterozygous for targeted defects in both Nf1 and p53 as
      well as Nf1 and Rb exhibit 3- and 2.5-fold increases in astrocyte proliferation
      in vivo, respectively, suggesting that abnormalities in Nf1- and p53/Rb-regulated
      pathways cooperate in the heterozygous state to confer a growth advantage for
      brain astrocytes. Collectively, these results provide evidence for a cell
      autonomous growth advantage in Nf1+/- astrocytes and suggest that some of the
      brain pathology in individuals with NF1 might result from reduced, but not
      absent, NF1 gene function.

PMID- 11246231
TI  - Repression of proinflammatory cytokine and inducible nitric oxide synthase (NOS2)
      gene expression in activated microglia by N-acetyl-O-methyldopamine: protein
      kinase A-dependent mechanism.
AB  - Excessive proinflammatory cytokine and NO production by activated microglia play
      a role in neurodegenerative disorders. To investigate whether the neuroprotectant
      N-acetyl-O-methyldopamine (NAMDA) downregulates genes associated with microglial
      activation, we measured gene expression of TNF-alpha, IL-1beta, inducible nitric
      oxide synthase (NOS2), and an associated cofactor synthesis gene, GTP
      cyclohydrolase I (GTPCH) in LPS-stimulated microglia cells in the presence or
      absence of NAMDA. The temporal pattern of cytokine gene expression showed that
      LPS (0.2 microg/ml) increased TNF-alpha and IL-1beta gene expression at 1 and 3
      h, which was repressed by cotreatment of NAMDA. Similarly, LPS also induced GTPCH
      and NOS2 gene expression at 3 and 6 h, and cotreatment of NAMDA repressed the
      induction with parallel reduction of nitrite, an oxidative metabolite of nitric
      oxide. Since transcription factor NF-kappaB is involved in regulating expression
      of these genes, the effects of NAMDA on NF-kappaB nuclear translocation and DNA
      binding in immunostimulated microglia were investigated. We found that neither
      LPS-induced NF-kappaB translocation nor DNA binding activity was affected by
      cotreatment with NAMDA in BV-2 microglia. On the other hand, NAMDA increased
      intracellular cAMP levels and potentiated LPS-induced phosphorylated cAMP
      responsive element binding protein (pCREB) expression. Treatment with adenosine
      3'5'-cyclic monophosphothioate, a specific inhibitor of cAMP-dependent protein
      kinase (PKA), reversed not only NAMDA-induced pCREB upregulation but also NAMDA
      induced repression of TNF-alpha and IL-1beta gene transcription. The data
      demonstrate that NAMDA represses LPS-induced proinflammatory cytokines gene
      expression via a cAMP-dependent protein kinase pathway. Thus, repressing
      proinflammatory cytokines and NOS2 gene expression in activated microglia by
      NAMDA may provide new therapeutic strategies for ischemic cerebral disease as
      well as other neurodegenerative diseases.

PMID- 11246232
TI  - Mitogenic response of adult rat olfactory ensheathing glia to four growth
      factors.
AB  - Olfactory ensheathing glia (EG) from adult rat proliferate slowly in vitro
      without added mitogens. The potential future use of EG in transplantation within
      the central nervous system to improve neural repair is dependent on identifying
      mitogens that will effectively expand EG without altering their phenotype. The
      mitogenic effects of heregulin (HRG), fibroblast growth factor 2 (FGF-2),
      platelet-derived growth factor BB (PDGF-BB), insulin-like growth factor 1 (IGF
      1), and forskolin (FSK) on cultured adult-derived rat EG were monitored by
      tritiated-thymidine labeling and p75 immunostaining. In serum-containing medium,
      HRG, FGF-2, PDGF-BB, IGF-1, and FSK were capable of stimulating EG proliferation,
      and the stimulation by these growth factors was potentiated by FSK. The
      combinations of HRG + FGF-2, HRG + PDGF-BB, HRG + IGF-1, FGF-2 + PDGF-BB, and FGF
      2 + IGF-1 all promoted EG proliferation in an additive manner. In serum-free
      medium, HRG and FGF-2 were mitogenic, but PDGF-BB, IGF-1 and FSK were not;
      however, FSK potentiated the stimulation by HRG and FGF-2, and the combination of
      HRG + FGF-2 promoted EG proliferation in an additive manner. This new information
      will be useful for the design of protocols to achieve sufficient numbers of adult
      derived EG for clinical purposes. This study also further establishes
      similarities between EG and Schwann cells.

PMID- 11246233
TI  - Astrocytes overexpressing Cu,Zn superoxide dismutase have increased resistance to
      oxidative injury.
AB  - Overexpression of Cu,Zn SOD (SOD1) can increase survival of neurons under some
      pathological conditions. Prior studies have shown, however, that SOD1
      overexpression can reduce neuronal survival during exposure to superoxide
      generators by a mechanism involving excess H(2)O(2) accumulation. Since
      astrocytes exhibit greater H(2)O(2) catabolism capacity than do neurons, the
      present study examined the effects of SOD1 overexpression on astrocyte survival
      under these conditions. Cultures were prepared from transgenic mice that
      overexpress human SOD1 and from nontransgenic littermate controls. Exposure to
      xanthine oxidase/hypoxanthine (XO/HPX) or menadione caused dose-dependent
      astrocyte death. In contrast to prior observations with neurons, astrocytes that
      overexpress SOD1 showed increased resistance to superoxide toxicity.
      Surprisingly, increased survival in SOD1 overexpressing cultures remained evident
      even when H(2)O(2) catabolism was inhibited by preincubation with aminotriazole
      (to block catalase) and buthionine sulfoximine (to deplete glutathione). These
      findings suggest differences in superoxide metabolism between neurons and
      astrocytes, and that the greater resistance of astrocytes to oxidative stress is
      due at least partly to factors other than greater glutathione peroxidase and
      catalase activity in astrocytes. GLIA 33:343-347, 2001. Published 2001 Wiley
      Liss, Inc.

PMID- 11246234
TI  - SMART: The microstent's ability to limit restenosis trial.
AB  - In this randomized, prospective, multicenter trial (n = 661) of patients with de
      novo or restenotic coronary lesions, 330 patients received the MicroStent(R) II
      (MSII), and 331 received the Palmaz-Schatz (PS) stent. The short-term procedural
      success rates were 94.4% and 95.7%, respectively (P = 0.47). The 30-day
      cumulative incidence of major adverse events [death, myocardial infarction, CVA,
      target lesion revascularization (TLR)] was 6.4% for the MSII and 4.5% for the PS
      stent (P = 0.31). The in-stent binary restenosis rate at 6 months was 25.2% for
      the MSII and 22.1% for the PS stent (P = 0.636). Using Kaplan-Meier estimates,
      the incidence of clinically driven TLR was 8.9% for the MSII and 9.2% for the PS
      stent at 180 days; at 270 days, it was 12.8% and 12.1%, respectively (P = 0.83).
      MSII and the PS stents were comparable with respect to short-term procedural
      success, complications, and late clinical and angiographic restenosis.

PMID- 11246236
TI  - Coronary perforation during percutaneous coronary intervention in the era of
      abciximab platelet glycoprotein IIb/IIIa blockade: an algorithm for percutaneous
      management.
AB  - Coronary perforation is an uncommon but potentially life-threatening complication
      of percutaneous coronary intervention. The use of both atheroablative
      technologies for coronary intervention and adjunctive platelet glycoprotein
      blockade pharmacology may increase the incidence of or risk for life-threatening
      bleeding complications following the occurrence of coronary artery perforation.
      The interventional database for 6,214 percutaneous coronary interventions
      performed between January 1995 and June 1999 was analyzed. Hospital charts and
      cine angiograms for all patients identified in the database as having had
      coronary perforation were reviewed. Coronary perforation complicated 0.58% of all
      procedures and was more commonly observed in patients with a history of
      congestive heart failure and following use of atheroablative interventional
      technologies (2.8%). There was no association of abciximab therapy with either
      the incidence of or classification for coronary perforation. Adverse clinical
      outcomes (death, emergency surgical exploration) were related to the angiographic
      classification of perforation and were more frequently observed in patients who
      experienced a class 3 coronary perforation. These data suggest that specific
      clinical and procedural demographic factors are associated with the occurrence
      and severity of angiographic coronary perforation. An angiographic perforation
      class-specific algorithm for treatment of coronary perforation is proposed.

PMID- 11246237
TI  - Coronary perforation: angioplasty out of control.

PMID- 11246238
TI  - Complications of cardiac catheterization in the current era: a single-center
      experience.
AB  - Consecutive cardiac catheterization procedures done over a 2-yr period (April
      1996 to March 1998) were prospectively analyzed to determine and characterize
      procedure-related complications (in-hospital and 1-mo follow-up), as they occur
      at present. During the study period, 11,821 procedures (7,953 diagnostic and
      3,868 therapeutic) were performed. The majority of procedures (> 60%) were done
      in high-risk patients. Stents were implanted in 33% of patients, and adjunctive
      abciximab was used in 6.6% of therapeutic procedures. The overall complication
      rate was 8% (3.6% of diagnostic procedures and 15.1% of therapeutic procedures).
      The procedure-related mortality rates were 0.2%, 0.1%, and 0.5% for total,
      diagnostic, and therapeutic procedures, respectively. Cardiac complications were
      seen in 3.9% (1.5% of diagnostic and 9% of therapeutic procedures). Emergency
      cardiac surgery was required in 0.05% of the diagnostic procedure group and 0.3%
      of the therapeutic procedure group (total, 0.1%). Despite marked changes in
      patient population and practice, the complication rates of cardiac
      catheterization remain very low.

PMID- 11246239
TI  - Complications of cardiac catheterization: what else is new?

PMID- 11246240
TI  - Impact of abciximab versus tirofiban on hospital length of stay for PCI patients.
AB  - The purpose of this retrospective study was to examine in a naturalistic setting
      the effect of abciximab versus tirofiban on hospital length of stay for patients
      undergoing percutaneous coronary intervention (PCI). Retrospective data were
      obtained from HCIASach's Clinical Pathways Database on 5,560 PCI patients who
      were administered either abciximab or tirofiban. Multivariate analysis was used
      to control for a wide range of factors (GPIIb/IIIa selection, patient
      demographics, insurance provider, health conditions, admission information, and
      hospital characteristics) that may influence hospital length of stay. Estimation
      was conducted via a two-stage sample selection model. After controlling for high
      risk indications and sources of selection bias, results indicate that receipt of
      abciximab was associated with significantly shorter lengths of hospital stays
      compared to tirofiban (1.01 fewer days; p < 0.001). In a subgroup analysis of
      patients having an acute myocardial infarction (AMI; n = 2,593), receipt of
      abciximab was also found to be associated with significantly shorter hospital
      stays compared to tirofiban (0.60 fewer days; p < 0.001). Results of this study
      indicate that patients who are administered abciximab versus tirofiban have
      significantly shorter hospital stays. This reduction in length of stay may imply
      potential cost offsets for PCI patients who receive abciximab.

PMID- 11246241
TI  - Efficacy of heparin-coated stent in early setting of acute myocardial infarction.
AB  - Primary stenting has been reported to be superior to balloon percutaneous
      transluminal coronary angioplasty (PTCA) in acute myocardial infarction (AMI) for
      recurrent ischemia, target lesion revascularization, and restenosis. However,
      concerns about early reocclusion or thrombosis after stenting in the very
      thrombotic environment of acute myocardial infarction still remain. Therefore,
      postprocedural short-term heparin or GpII(b)/III(a) receptor blockades has been
      used. The aim of our study was to evaluate the safety, feasibility, and long-term
      efficacy of heparin-coated stent in the early setting of AMI without
      postprocedural heparin or GpII(b)/III(a) receptor blockade infusion. We studied
      102 consecutive patients presenting to cardiac catheterization laboratory < or =
      6 hr from the onset of chest pain. No patients who were implanted with heparin
      coated stents received heparin or GpII(b)/III(a) receptor blockade infusion after
      the procedures, not even patients who showed an angiographically large thrombus
      burden before stenting. Patients were evaluated for clinical endpoints at 30 days
      and 6 months. Coronary angiography was required for all patients at 2 weeks and 6
      months after the procedure. Angiographic and procedural successes were 100% and
      98%, respectively. Two patients (2%) died of heart failure without evidence of
      reocclusion of stented vessel during the hospitalization and 4 (4%) additional
      patients died of refractory heart failure within the first 6 months. Major
      bleeding complication occurred in one patient (1%). Recurrent myocardial
      infarction developed in one patient at 4 months. Early angiographic follow up at
      2 weeks was performed in 88% of all patients, none of whom showed thrombotic
      stent occlusion. Six-month angiographic follow-up was completed in 71%(64/91) of
      eligible patients and binary restenosis was present in 17.2% of stented vessels.
      Eight(8%) patients underwent repeat PTCA. Cardiac event-free survival rate at 6
      months was 86.3%. This study demonstrates that heparin-coated stents are safe in
      the early setting of acute myocardial infarction and no additional heparin
      infusion after stenting is necessary, which may reduce bleeding complications.
      Angiographic restenosis rate compares favorably to the binary restenosis rate
      from other studies with uncoated stents.

PMID- 11246242
TI  - True potential of stents.

PMID- 11246243
TI  - Comparison of low-volume versus standard-volume left ventriculography.
AB  - Left ventriculography provides useful information about cardiac function, wall
      motion, and mitral regurgitation (MR). However, standard volumes of contrast
      agent frequently are associated with ventricular ectopy. This study compares the
      use of low-volume (Low-vol) ventriculography to standard volume (Std-vol)
      ventriculography. Left ventricular (LV) ejection fraction (EF), changes in LV end
      diastolic pressure (LVEDP), the incidence of ectopy, and > 2+ MR were
      prospectively determined from the random order use of standard (15 mL/ second for
      3 sec) and low-volume (15 mL/sec for 1 sec) contrast agents in 102 patients. Each
      patient served as his or her own control. Twenty-seven percent of the 204
      ventriculograms were not interpretable due to ectopy. Ectopy > or = 3 beats was
      more common with Std-vol angiograms (41% vs. 14%, P < 0.001). Post-injection
      LVEDP increased from baseline after both Std-vol and Low-vol injections (P <
      0.001). In patients for whom both angiograms could be interpreted (n = 58), no
      differences were noted between planimetered EFs (Low-vol = 61 +/- 20% vs. Std-vol
      = 62 +/- 20%, with r = 0.87; P < 0.001). A Bland-Altman test of agreement
      indicated a mean difference +/- 95% CI = -2 +/- 19%. Low-volume ventriculography
      reduces contrast load and ectopy while providing similar estimates of EF compared
      with standard volumes.

PMID- 11246244
TI  - Low-volume left ventriculography: the heart of the matter is large or small.

PMID- 11246245
TI  - Comparison of myocardial fractional flow reserve and intravascular ultrasound for
      the assessment of slotted-tube stents.
AB  - Intravascular ultrasound (IVUS) and myocardial fractional flow reserve (FFR) have
      been reported to provide similar results for assessment of coil stent deployment.
      Their relative value in slotted-tube stents has not been investigated. Fourteen
      patients subjected to coronary angioplasty and IVUS-guided elective stenting with
      a slotted-tube stent underwent IVUS assessment and FFR measurement following
      stent implantation at inflation pressures of 12 and 18 atm. FFR values (mean +/-
      SD) preangioplasty, postangioplasty, and poststenting at 12 atm and 18 atm, were
      0.58 +/- 0.07, 0.83 +/- 0.05, 0.94 +/- 0.02, and 0.94 +/- 0.02, respectively.
      After inflation at 12 atm, the area under the receiver operating characteristic
      (ROC) curve for the concordance of IVUS and FFR measurements was 0.89 (P = 0.02).
      Six patients had either an abnormal IVUS (n = 2) or FFR < 0.94 (n = 1) or both
      abnormal IVUS and FFR < 0.94 (n = 3) after the first inflation and had a second
      inflation at 18 atm. The area under the ROC curve for the concordance between
      IVUS and FFR final measurements was 0.855 (P = 0.10). Perfect concordance between
      IVUS and FFR was seen only for FFR values less than 0.91 or larger than 0.94.
      Overall, IVUS and FFR have substantial concordance with respect to slotted-tube
      stent deployment. However, FFR values between 0.91 and 0.94 after inflation are
      difficult to interpret.

PMID- 11246247
TI  - Effects of left atrial compliance on left atrial pressure in pure mitral
      stenosis.
AB  - In mitral stenosis (MS), left atrial (LA) pressure is commonly elevated because
      of increased LA afterload. There is a wide spectrum of LA pressure in patients
      with MS, however, despite a similar mitral valve orifice area. LA compliance is
      an important determinant of both cardiovascular performance and pathological
      physiology. Few data are available, however, regarding the effects of LA
      compliance on LA pressure. We hypothesized that LA pressure may be higher in
      patients with decreased LA compliance. We analyzed the right heart and
      transseptal catheterization data in 47 patients (41 female, mean age 40 +/- 10
      years) with pure MS and sinus rhythm. The magnitude of LA a and v waves was
      measured from transseptal catheterization. Fick's method was used to determine
      cardiac output. LA compliance was calculated by dividing the systolic rise in LA
      pressure (DeltaP(LA) = P(LA(v)) - P(LA(x))) into the stroke volume. LA size,
      mitral valve area (MVA), mean diastolic pressure gradient (MG), left ventricular
      (LV) end-diastolic and end-systolic dimensions were obtained by using two
      dimensional and Doppler echocardiography. Multiple regression analysis was
      performed to identify independent factors determining LA pressure. The mean MVA
      was 0.95 +/- 0.22 cm(2). MG and LA dimension were 11.2 +/- 5.2 mm Hg and 50.6 +/-
      5.2 mm, respectively. The mean LA pressure and cardiac output obtained by cardiac
      catheterization were 23.4 +/- 8.4 mm Hg and 4.3 +/- 1.5 L/min, respectively. The
      calculated LA compliance was 4.9 +/- 2.8 cm(3)/mm Hg. Univariate analysis showed
      that factors associated with increased LA pressure were smaller MVA (r = -0.33, P
      < 0.05), higher MG (r = 0.69, P < 0.01) and lower LA compliance (r = -0.55, P <
      0.01); among them, MG (beta coefficient 0.59, SE 0.19, P < 0.01) and LA
      compliance (beta coefficient -0.26, standard error 0.34, P < 0.05) were the
      strongest predictors of LA pressure. In conclusion, LA compliance, along with MG
      that reflects the severity of MS, is an important contributing factor determining
      LA pressure in patients with pure MS and sinus rhythm.

PMID- 11246248
TI  - Suitability of the Cordis Stabilizer marker guide wire for quantitative coronary
      angiography calibration: an in vitro and in vivo study.
AB  - Catheters usually are used for calibration purposes in quantitative coronary
      angiography (QCA). The systematic and random errors in these calibration factors
      (CFs) are dependent on the size and quality of the catheters and limited by out
      of-plane magnification (OPM). Theoretically, a guide wire with evenly spaced
      marker bands would solve many of these potential problems. For this reason, we
      tested the Cordis Stabilizer marker wire, featuring 10 radiopaque platinum marker
      bands 15 mm apart, in in vitro and in vivo studies. To assess the effect of
      foreshortening, wires were positioned in a tube phantom; a centimeter grid was
      used as the gold standard. Radiographic images were acquired at 5-inch and 7-inch
      image-intensifier sizes, 512(2) and 1,024(2) matrix sizes and angulations from 0
      degrees to 70 degrees in steps of 10 degrees. It was concluded that the relative
      errors in CFs are less than 7% if the foreshortening angles remain less than 20
      degrees. In DICOM images of 15 patients, 65 measurements were taken after
      calibration on an 8F catheter and on a guide wire positioned in the coronary
      lesion. In all but two cases, the wire CFs were larger than the catheter CFs
      (relative difference, 24.7 +/- 19.6%). The measurements were divided into four
      groups: (I) no apparent OPM or foreshortening (n = 7), (II) only OPM (n = 4),
      (III) only foreshortening (n = 10), and (IV) the combination of both (n = 44). In
      group I (no OPM or foreshortening) the QCA results were similar using the guide
      wire or catheter as the calibration device (relative CF difference, 2.9% only).
      In group III the diameters were overestimated using the guide wire (obstruction
      diameter difference, 0.22 +/- 0.11 mm; reference diameter difference, 0.35 +/-
      0.06 mm). For only OPM (group II) and the combination of OPM and foreshortening
      (group IV), the lesion length was underestimated on average by 2.4 mm using the
      catheter instead of the guide wire. In conclusion, if accurate assessment of the
      lesion length is important, the marker wire should be used for calibration
      purposes. For vessel diameter measurements, the conventional catheter calibration
      approach is the method of choice.

PMID- 11246249
TI  - Catheter-based electromechanical mapping to assess regional myocardial function:
      a comparative analysis with transthoracic echocardiography.
AB  - Recent studies using a nonfluoroscopic three-dimensional left ventricular mapping
      system showed considerable changes in voltage potentials and mechanical activity
      detected in ischemic and infarcted myocardial regions with mechanical
      dysfunction. This study examined the electromechanical characteristics in
      relation to regional wall motion assessed by echocardiography in patients with
      coronary artery disease. A 12-segment model of mapping (apical, mid, basal of
      septal, anterior, lateral, and inferior/posterior segments) was compared to echo
      wall motion score in 74 patients (836 segments). Unipolar voltage and local
      endocardial shortening signals were distinguished according to graded echo
      segmental rest scores (0 = normal, 1 = mild hypokinesis, 2 = moderate
      hypokinesis, 3 = severe hypokinesis, 4 = akinesis). Results show a significant
      difference in voltage potentials and shortening values in groups distinguished
      according to echocardiography motion score. The average voltage potentials and
      shortening values were highest in myocardial segments with normal or slightly
      reduced contractility and lowest in myocardial segments with moderate to severely
      impaired contractility scores (voltage: 12.3 +/- 5.0, 12.1 +/- 5.3, 10.7 +/- 5.4,
      8.7 +/- 3.9, 7.1 +/- 3.0 mV, P = 0.0001; local shortening: 9.7 +/- 6.5, 8.4 +/-
      5.9, 8.0 +/- 5.4, 5.6 +/- 6.3, 5.1 +/- 4.6%, P = 0.0001 in regions with segmental
      scores of 0, 1, 2, 3, 4 by echo, respectively). Using receiver-operating curve
      calculations, the area under the curve was 0.72 +/- 0.06 (voltage) and 0.67 +/-
      0.05 (local shortening) without a significant difference between the two curves.
      The 90% thresholds for defining preserved vs. impaired contractility were 12.8
      and 5.6 mV for voltage and 12.6% and 1.6% for local shortening. We conclude that
      electromechanical mapping correlates with regional changes in wall motion scores
      assessed by echo, showing a gradual proportional decrease in measured voltage and
      shortening signals in segments with impaired function.

PMID- 11246250
TI  - Biosensibility of viability: NOGA or no good?

PMID- 11246251
TI  - Stent implantation for superior vena cava occlusion after the Mustard operation.
AB  - A 25-year-old man who had undergone a Mustard repair for complete transposition
      of the great arteries 21 years previously developed complete occlusion of the
      superior vena cava and obstruction of the inferior vena cava. Transcatheter
      recanalization was performed using needle puncture of the superior obstruction
      followed by stent implantation into both systemic venous pathways with relief of
      obstructive symptoms.

PMID- 11246253
TI  - Transcatheter closure of a 16 mm hypertensive patent ductus arteriosus with the
      Amplatzer muscular VSD occluder.
AB  - There is little experience with transcatheter closure of very large, hypertensive
      patent ductus arteriosus. We present a case of successful closure of a 16 mm
      ductus with the Amplatzer VSD occluder, a device originally designed for
      transcatheter closure of congenital muscular ventricular septal defects. To our
      best knowledge this is the largest ductus ever closed by an interventional
      technique.

PMID- 11246252
TI  - Percutaneous stent placement as treatment for an infant with superior vena cava
      syndrome.
AB  - The percutaneous use of stents for the treatment of superior vena cava (SVC)
      syndrome is well described in the adult population. We report the successful use
      of intravascular stents to treat an infant with severe SVC syndrome.

PMID- 11246254
TI  - Left main crumpling during left anterior descending angioplasty: hitherto
      unreported location for the "accordion effect".
AB  - Vessel wall shortening and deformity due to "arterial telescoping" is a not
      infrequent reversible phenomenon that occurs during coronary angioplasty and is
      associated with the advancement of a stiff wire through elongated and tortuous
      segments, with straightening of the artery and deep guiding catheter introduction
      beyond the coronary ostium. We present the first described case of the accordion
      effect involving the left main coronary artery. On detecting arterial crumpling,
      it is essential to make a differential diagnosis between the accordion syndrome
      and PTCA potential complications (spasm, thrombosis and dissection), to avoid
      further therapeutic intervention.

PMID- 11246255
TI  - Percutaneous transluminal angioplasty of ostial lesions of internal mammary
      artery grafts.
AB  - The internal mammary artery (IMA) is currently the best graft for coronary bypass
      surgery and is therefore preferentially anastomosed to major arteries, usually
      the left anterior descending (LAD) artery. This graft may develop a stenosis,
      most often at the distal anastomosis. Ostial stenoses are rare and their
      pathophysiology uncertain. While angioplasty of distal anastomotic lesions
      provides adequate results, the very small number of published cases of
      angioplasty of ostial lesions explains the lack of knowledge on results of this
      type of procedure. The authors report six procedures of this type on five
      patients, including two with stenting. The primary success rate was 100%, with
      only one hospital complication in the form of pulmonary edema. Mean follow-up for
      35 months revealed one sudden death due to probable restenosis, another death 3
      years after angioplasty from rapid fatal shock without complementary
      investigation, and one case of unstable angina secondary to intrastent
      restenosis. These results suggest that this type of angioplasty is technically
      feasible with low risk, and that the restenosis rate seems relatively high,
      potentially presenting as sudden death, in the same way as unprotected dilatation
      of the native left main artery. A very close clinical follow-up of these patients
      is therefore necessary, with angiographic control in case of suspected ischemia.

PMID- 11246256
TI  - Percutaneous treatment of symptomatic vertebral artery stenosis with coronary
      stents.
AB  - Atherosclerotic disease of the vertebral artery can pose a significant clinical
      problem. The treatment of that disease is not uniformly accepted. We report two
      cases of patients with vertebral basilar insufficiency due to stenosis of the
      vertebral artery origins and contralateral occlusions that were treated
      percutaneously with coronary stent placement.

PMID- 11246257
TI  - Congenital origin of the left main coronary artery from the innominate artery in
      a 37-year-old man with syncope and right ventricular dysplasia.

PMID- 11246258
TI  - In vitro and in vivo comparison of three different intravascular ultrasound
      catheter designs.
AB  - Intravascular ultrasound (IVUS) is an invasive imaging modality, which provides
      detailed two-dimensional images of blood vessels. There are currently two
      different types of IVUS catheters available, namely, the phased-array and the
      mechanical designs. The operating ultrasound frequency of these catheters ranges
      from 20 to 40 MHz. This study sought to evaluate the image quality, accuracy of
      diameter and pullback length measurements, and catheter handling characteristics
      of three different IVUS catheters currently available for clinical use using both
      in vitro phantom models and in patients undergoing percutaneous coronary
      intervention (PCI). In gelatin phantom models, image quality assessed on a
      semiquantitative scale was significantly different between the three IVUS
      catheters (P = 0.01) with the 40-MHz catheter providing the best images. Accuracy
      of lumen diameter measurements, when compared to optical microscopy, were similar
      between the three IVUS catheter designs (all R(2) = 0.99). There were no
      significant differences in accuracy of pullback length measurements in vitro
      between the three designs. However, there were differences in the performance of
      the three IVUS catheters when used for preinterventional imaging in patients
      undergoing PCI. Both mechanical IVUS catheters were associated with lower
      procedural, fluoroscopy, and lesion crossing times compared to the phased-array
      catheter (all P < 0.05). There were no significant differences between the
      catheters during postinterventional IVUS imaging. There were also small but
      potentially important differences with regards to clinical events and
      complications associated with the use of the different IVUS catheters during the
      PCI procedures, reflecting differences in catheter design.

PMID- 11246259
TI  - Coronary angiography using 4 Fr catheters with acisted power injection: A
      randomized comparison to 6 Fr manual technique and early ambulation.
AB  - Coronary angiography using 4 Fr catheters may reduce access site complications,
      promote better utilization of outpatient facilities, but at a cost of suboptimal
      image quality. To determine whether 4 Fr diagnostic angiography with power
      injection (Acist, Minneapolis, MN) was equivalent to 6 Fr manual technique, 101
      unselected patients were randomized to transfemoral coronary angiography with 4
      or 6 Fr catheters. Procedural characteristics, angiographic quality scores, and
      results of 90 min ambulation were analyzed. Coronary angiographic quality scores
      using 4 Fr and 6 Fr catheters were equivalent (left coronary artery 4.73 +/- 0.6
      vs. 4.80 +/- 0.65, P = 0.28; right coronary artery 4.98 +/- 90.13 vs. 4.97 +/-
      0.16, P = 0.48). However, 4 Fr left ventriculographic image score was lower (4.53
      +/- 0.68 vs. 4.83 +/- 0.42, P = 0.0002), attributed, in part, to a smaller
      injected contrast volume (32 +/- 11 vs. 37 +/- 4 mL, P = 0.001). The total study
      contrast volume was significantly less in the 4 Fr group (119 +/- 35 vs. 159 +/-
      52 mL, P = 0.001). Complications related to early ambulation at 90 min were
      similar and minimal in both groups. Compared to 6 Fr manual contrast injection
      technique, diagnostic angiography through 4 Fr catheters with power contrast
      injection resulted in equivalent coronary angiographic image quality, slightly
      reduced but diagnostic left ventricular image quality, and significantly less
      contrast volume. Four Fr angiography facilitates early ambulation without
      compromising safety and image quality.

PMID- 11246260
TI  - Are you dyed-in-the-wool?

PMID- 11246261
TI  - Assessment of NOGA catheter stability during the entire cardiac cycle by means of
      a special needle-tipped catheter.
AB  - The NOGA system maps regional myocardial function and delivers local catheter
      based therapeutics, requiring stability and precise localization of the catheter
      tip throughout the cardiac cycle. A special catheter having a retractable needle
      at its tip was used to compare tip stability with and without needle insertion
      into the myocardium, assuming this prevents catheter slippage. For multiple sites
      in seven pig left ventricles, we recorded sets of three consecutive point
      locations: pre-, post-, and during needle insertion. In-point location stability
      (LocStab), defined as the mean displacement between catheter tip trajectories of
      two consecutive cardiac cycles at a specific point, did not differ among the
      three groups of points (mean, 1.33 +/- 0.61 mm; P = 0.37 by ANOVA), indicating
      that trajectories are equally stable and repeatable with or without needle
      insertion. Between-point LocStab(p1,p2), i.e., displacement between the
      trajectories of two different points (p1 and p2) at the same location, was not
      increased when p1 = a needle insertion point and p2 = a noninsertion point,
      compared to both p1,p2 = noninsertion points, suggesting that slippage of
      noninsertion points is negligible. In conclusion, catheter tip trajectories at
      any location are highly stable throughout the cardiac cycle.

PMID- 11246262
TI  - Catheter-based device closure of Fontan fenestrations.

PMID- 11246266
TI  - Computer simulations for biological aging and sexual reproduction.
AB  - The sexual version of the Penna model of biological aging, simulated since 1996,
      is compared here with alternative forms of reproduction as well as with models
      not involving aging. In particular we want to check how sexual forms of life
      could have evolved and won over earlier asexual forms hundreds of million years
      ago. This computer model is based on the mutation-accumulation theory of aging,
      using bits-strings to represent the genome. Its population dynamics is studied by
      Monte Carlo methods.

PMID- 11246267
TI  - Effect of leaf essential oil from Piper solmsianum C.DC. in mice behaviour.
AB  - The essential oil from Piper solmsianum leaves and its major compound (sarisan)
      were tested to verify their influences upon mice behaviour. The essential oil was
      obtained by hydrodistillation in a modified Clevenger extractor and analysed by
      GC/ MS. This analysis revealed in the oil the presence of monoterpenes,
      sesquiterpenes and of arylpropanoids. The compound sarisan, a myristicin
      analogue, was isolated from the oil to perform the pharmacological tests.
      Emulsions of the oil and of sarisan (5.0 and 10.0% v/v) were used in the tests.
      Pentobarbital (30 mg/ kg s.c.) or diazepam (2.5 mg/ kg s.c.) were tested as
      standard drugs to verify depressant or anxiolytic effects, respectively. Both
      essential oil and sarisan showed to have exciting and depressant effects in the
      tested animals.

PMID- 11246268
TI  - Bacterioplankton abundance, biomass and production in a Brazilian coastal lagoon
      and in two German lakes.
AB  - The bacterioplanktonic abundance, biomass, and production within a tropical
      lagoon (Cabiunas, Brazil) and two temperate lakes (Stechlin and Dagow, Germany)
      were compared. Bacterial abundance and production were significantly different
      among the three water bodies. The lowest bacterial production (0.8 microg C l(-1)
      d(-1)) was observed in the tropical Cabiunas Lagoon despite its higher mean
      temperature and dissolved organic carbon concentration. Highest bacterioplankton
      abundance (2.6 x 10(9) cells l(-1)) and production (68.5 microg C l(-1) d(-1))
      were measured in eutrophic Lake Dagow. In oligotrophic Lake Stechlin, the lowest
      bacterial biomass (48.05 microg C l(-1)) was observed because of lower bacterial
      biovolume (0.248 microm(3)) and lower bacterial abundance. Bacterial populations
      in the temperate lakes show higher activity (production/biomass ratio) than in
      the tropical lagoon. The meaning of isotopic dilution and leucine incorporation
      by non-bacterial micro-organisms were evaluated in the oligotrophic temperate
      system. Leucine uptake by non-bacterial micro-organisms did not have significant
      influence on bacterial production.

PMID- 11246269
TI  - Alcohol and atherosclerosis.
AB  - Atherosclerosis is manifested as coronary artery disease (CAD), ischemic stroke
      and peripheral vascular disease. Moderate alcohol consumption has been associated
      with reduction of CAD complications. Apparently, red wine offers more benefits
      than any other kind of drinks, probably due to flavonoids. Alcohol alters
      lipoproteins and the coagulation system. The flavonoids induce vascular
      relaxation by mechanisms that are both dependent and independent of nitric oxide,
      inhibits many of the cellular reactions associated with atherosclerosis and
      inflammation, such as endothelial expression of vascular adhesion molecules and
      release of cytokines from polymorphonuclear leukocytes. Hypertension is also
      influenced by the alcohol intake. Thus, heavy alcohol intake is almost always
      associated with systemic hypertension, and hence shall be avoided. In individuals
      that ingest excess alcohol, there is higher risk of coronary occlusion,
      arrhythmias, hepatic cirrhosis, upper gastrointestinal cancers, fetal alcohol
      syndrome, murders, sex crimes, traffic and industrial accidents, robberies, and
      psychosis. Alcohol is no treatment for atherosclerosis; but it doesn't need to be
      prohibited for everyone. Thus moderate amounts of alcohol (1-2 drinks/day),
      especially red wine, may be allowed for those at risk for atherosclerosis
      complications.

PMID- 11246270
TI  - Multidrug resistance in tumour cells: characterization of the multidrug resistant
      cell line K562-Lucena 1.
AB  - Multidrug resistance to chemotherapy is a major obstacle in the treatment of
      cancer patients. The best characterised mechanism responsible for multidrug
      resistance involves the expression of the MDR-1 gene product, P-glycoprotein.
      However, the resistance process is multifactorial. Studies of multidrug
      resistance mechanisms have relied on the analysis of cancer cell lines that have
      been selected and present cross-reactivity to a broad range of anticancer agents.
      This work characterises a multidrug resistant cell line, originally selected for
      resistance to the Vinca alkaloid vincristine and derived from the human
      erythroleukaemia cell K562. This cell line, named Lucena 1, overexpresses P
      glycoprotein and have its resistance reversed by the chemosensitisers verapamil,
      trifluoperazine and cyclosporins A, D and G. Furthermore, we demonstrated that
      methylene blue was capable of partially reversing the resistance in this cell
      line. On the contrary, the use of 5-fluorouracil increased the resistance of
      Lucena 1. In addition to chemotherapics, Lucena 1 cells were resistant to
      ultraviolet A radiation and hydrogen peroxide and failed to mobilise
      intracellular calcium when thapsigargin was used. Changes in the cytoskeleton of
      this cell line were also observed.

PMID- 11246275
TI  - Bacillary angiomatosis: description of 13 cases reported in five reference
      centers for AIDS treatment in Rio de Janeiro, Brazil.
AB  - The aim of this case series was to describe the clinical, laboratory and
      epidemiological characteristics and the presentation of bacillary angiomatosis
      cases (and/or parenchymal bacillary peliosis) that were identified in five public
      hospitals of Rio de Janeiro state between 1990 and 1997; these cases were
      compared with those previously described in the medical literature. Thirteen case
      patients were enrolled in the study; the median age was 39 years and all patients
      were male. All patients were human immunodeficiency virus type 1 (HIV-1) infected
      and they had previous or concomitant HIV-associated opportunistic infections or
      malignancies diagnosed at the time bacillary angiomatosis was diagnosed. Median
      T4 helper lymphocyte counts of patients was 96 cells per mm(3). Cutaneous
      involvement was the most common clinical manifestation of bacillary angiomatosis
      in this study. Clinical remission following appropriate treatment was more common
      in our case series than that reported in the medical literature, while the
      incidence of relapse was similar. The frequency of bacillary angiomatosis in HIV
      patients calculated from two of the hospitals included in our study was 1.42
      cases per 1000 patients, similar to the frequencies reported in the medical
      literature. Bacillary angiomatosis is an unusual opportunistic pathogen in our
      setting.

PMID- 11246276
TI  - Heparin-antivenom association: differential neutralization effectiveness in
      Bothrops atrox and Bothrops erythromelas envenoming.
AB  - Heparin, in some regions of Brazil has been used in the treatment of bothropic
      accidents, but the data found in the literature are inconclusive about its
      effectiveness. The venoms of Bothrops atrox and of B. erythromelas were
      characterized according to their biological activities. The capacity of heparin
      in neutralizing these activities was tested with doses of 3 and 6 IU in isolated
      form and associated to Antibothropic Serum (ABS). It was verified that heparin,
      in doses of 3 and 6 IU, was not effective in neutralizing the desfibrinating and
      edema-forming activities of B. atrox venom and the hemorrhagic and coagulant
      actions of both venoms. Heparin diminished the effectiveness of the ABS in the
      neutralization of the hemorrhagic and edema-forming activities of the B. atrox
      venom. However, heparin in the 6 IU dose was capable of neutralize the edema
      forming of the B. erythromelas and increase the effectiveness of the ABS. Heparin
      also neutralized the phospholipasic A2 activity of B. atrox (14.3%) and B.
      erythromelas (28.0%) venoms. For B. erythromelas venom, the associated treatment,
      heparin and ABS, was more effective in the neutralization of its lethal activity.

PMID- 11246277
TI  - Hepatitis C virus seroprevalence and risk factors among patients with HIV
      infection.
AB  - The objective of this study was to evaluate the prevalence and risk factors
      associated with HCV infection in a group of HIV seropositive patients. We
      analyzed the medical records of 1,457 patients. All patients were tested for HCV
      infection by third generation ELISA. Whenever possible, a sample of the positive
      patients was also tested for HCV by PCR. HCV positive patients were analyzed
      according to their risk factors for both infections. The prevalence of anti-HCV
      positive patients was 17.7% (258 patients). Eighty-two (82) of these patients
      were also tested by PCR and 81 were positive for HCV virus (98%). One hundred
      fifty-one (58.5%) were intravenous drug users (IDU); 42 (16.3%) were sexual
      partners of HIV patients; 23 (8.9%) were homosexual males; 12 (4.7%) had received
      blood transfusion; 61 (17.5%) had promiscuous sexual habits; 14 (5.4%) denied any
      risk factor; 12 (4.7%) were sexual partners of IDU. Two hundred four patients
      mentioned only one risk factor. Among them, 28 (10.9%) were sexual partners of
      HIV-positive patients. Although intravenous drug use was the most important risk
      factor for co-infection, sexual transmission seemed to contribute to the high HCV
      seroprevalence in this group of patients.

PMID- 11246279
TI  - hsp65 PCR-restriction enzyme analysis (PRA) for identification of mycobacteria in
      the clinical laboratory.
AB  - More than 70 species of mycobacteria have been defined, and some can cause
      disease in humans, especially in immunocompromised patients. Species
      identification in most clinical laboratories is based on phenotypic
      characteristics and biochemical tests and final results are obtained only after
      two to four weeks. Quick identification methods, by reducing time for diagnosis,
      could expedite institution of specific treatment, increasing chances of success.
      PCR restriction-enzyme analysis (PRA) of the hsp65 gene was used as a rapid
      method for identification of 103 clinical isolates. Band patterns were
      interpreted by comparison with published tables and patterns available at an
      Internet site (http://www.hospvd.ch:8005). Concordant results of PRA and
      biochemical identification were obtained in 76 out of 83 isolates (91.5%).
      Results from 20 isolates could not be compared due to inconclusive PRA or
      biochemical identification. The results of this work showed that PRA could
      improve identification of mycobacteria in a routine setting because it is
      accurate, fast, and cheaper than conventional phenotypic identification.

PMID- 11246278
TI  - Etiology of acute diarrhea among children in Ribeirao Preto-SP, Brazil.
AB  - To study the main enteropathogens causing diarrhea in the region of Ribeirao
      Preto regarding serogroups and serotypes, the feces of 1836 children under 10
      years old, from both sexes, attack of acute gastroenteritis, were analysed during
      a period of 4 years in Adolfo Lutz Institute - Ribeirao Preto, SP. The pathogens
      identified by standard methods were the following: Escherichia coli, Salmonella
      spp., Shigella spp., Campylobacter spp., Yersinia spp., and Cryptosporidium spp.
      Positive samples were 22.8% (419) with 1.7% association of pathogens. Larger
      isolates were mainly from children 0 to 11 months old. Enteropathogenic E. coli
      (EPEC) was most frequent (8.7%) with predominance of serogroup O119 (40.2%),
      followed by Shigella (6.2%), 63.6% of which S. sonnei.

PMID- 11246280
TI  - Experimental dermatophytosis in hamsters inoculated with Trichophyton
      mentagrophytes in the cheek pouch.
AB  - This study presents the results of T. mentagrophytes inoculation in the cheek
      pouch of the hamster, an immunologically privileged site. Forty two animals were
      used: 21 inoculated with 10(6) fungi in the cheek pouch (group 1) and 21
      inoculated initially with 10(6) fungi in the foot pad and 15 days later in the
      cheek pouch, with the same amount of fungi (group 2). Animals were sacrificed at
      20 hours, 3, 7, 14, 30, 60, and 120 days; samples from inoculated cheek pouch,
      and foot pads submitted to the foot pad test (FPT), were collected. Independent
      of group and time of evolution of infection, animals did not develop delayed
      hypersensitivity evaluated through the FPT. The pre-inoculation of fungi in the
      foot pad did not change the morphology of lesions induced in the cheek pouch.
      Therefore, in animals of group 1 and 2, the introduction of the fungus in the
      cheek pouch resulted in focal lesion composed of a sterile acute inflammatory
      infiltrate, with abscess formation that evolved to a macrophagic reaction, and
      later to resolution even in the absence of immune response detectable by FPT. Our
      results indicate that in spite of the important role of the immune response in
      the spontaneous regression of dermatophytosis, other factors are also an integral
      part in the defense against this fungal infection.

PMID- 11246281
TI  - Treatment of pemphigus vulgaris and pemphigus foliaceus: experience with 71
      patients over a 20 year period.
AB  - Forty one cases of pemphigus vulgaris and thirty cases of pemphigus foliaceus
      were investigated at Hospital Universitario Clementino Fraga Filho from 1978 to
      1999. They were divided into two treatment groups: one group received up to 100
      mg of oral prednisone daily and the other group received >120 mg daily. The dose
      up to 100 mg provided good initial control of pemphigus vulgaris and pemphigus
      foliaceus and did not increase the mortality rate associated to disease. The dose
      >120 mg induced higher morbidity. These data allowed us to establish a regimen of
      oral prednisone (1-2 mg/kg/daily) with maximum of 120 mg daily in the treatment
      of pemphigus vulgaris and pemphigus foliaceus.

PMID- 11246282
TI  - Interrupting Chagas disease transmission in Venezuela.
AB  - The interruption of vectorial transmission of Chagas disease in Venezuela is
      attributed to the combined effects of ongoing entomoepidemiological surveillance,
      ongoing house spraying with residual insecticides and the concurrent building and
      modification of rural houses in endemic areas during almost five decades. The
      original endemic areas which totaled 750,000 km(2), have been reduced to 365,000
      km(2). During 1958-1968, initial entomological evaluations carried out showed
      that the house infestation index ranged between 60-80%, the house infection index
      at 8-11% and a house density index of 30-50 triatomine bugs per house. By 1990
      98, these indexes were further reduced to 1.6-4.0%, 0.01-0.6% and 3-4 bugs per
      house respectively. The overall rural population seroprevalence has declined from
      44.5% (95% C.I.: 43.4-45.3%) to 9.2% (95% C.I.: 9.0-9.4%) for successive grouped
      periods from 1958 to 1998. The annual blood donor prevalence is firmly
      established below 1%. The population at risk of infection has been estimated to
      be less than four million. Given that prevalence rates are stable and appropriate
      for public health programmes, consideration has been given to potential biases
      that may distort results such as: a) geographical differences in illness or
      longevity of patients; b) variations in levels of ascertainment; c) variations in
      diagnostic criteria; and d) variations in population structure, mainly due to
      appreciable population migration. The endemic areas with continuous transmission
      are now mainly confined to piedmonts, as well as patchy foci in higher
      mountainous ranges, where the exclusive vector is Rhodnius prolixus. There is
      also an unstable area, of which landscapes are made up of grasslands with
      scattered broad-leaved evergreen trees and costal plains, where transmission is
      very low and occasional outbreaks are reported.

PMID- 11246283
TI  - Whipple's disease. Report of five cases with different clinical features.
AB  - Whipple's disease (WD) is a rare systemic disease of infectious etiology which
      involves the small intestine but can virtually affect any organ. We present here
      five cases (four males and one female) ranging in age from 20 to 59 years. All
      patients had intestinal involvement associated or not with clinical
      manifestations linked to this organ. Vegetation in the tricuspid valve was
      observed in one patient, suggesting endocarditis caused by Tropheryma whippelii,
      with disappearance of the echocardiographic alterations after treatment. In one
      of the male patients the initial clinical manifestation was serologically
      negative spondylitis, with no diarrhea occurring at any time during follow-up.
      Ocular involvement associated with intestinal malabsorption and significant
      weight loss were observed in one case. In the other two cases, diarrhea was the
      major clinical manifestation. All patients were diagnosed by histological
      examination of the jejunal mucosa and, when indicated, of extraintestinal tissues
      by light and electron microscopy. After antibiotic treatment, full remission of
      symptoms occurred in all cases. A control examination of the intestinal mucosa
      performed after twelve months of treatment with sulfamethoxazole-trimethoprim
      revealed the disappearance of T. whippelii in four patients. The remaining
      patient was lost to follow-up.

PMID- 11246284
TI  - Proposal of abolition of the skin sensitivity test before equine rabies immune
      globulin application.
AB  - An epizootic outbreak of rabies occurred in 1995 in Ribeirao Preto, SP, with 58
      cases of animal rabies (54 dogs, 3 cats and 1 bat) confirmed by the Pasteur
      Institute of Sao Paulo, and one human death. The need to provide care to a large
      number of people for the application of equine rabies immune globulin (ERIG)
      prevented the execution of the skin sensitivity test (SST) and often also the
      execution of desensitization, procedures routinely used up to that time at the
      Emergency Unit of the University Hospital of the Faculty of Medicine of Ribeirao
      Preto, University of Sao Paulo (EU-UHFMRP-USP), a reference hospital for the
      application of heterologous sera. In view of our positive experience of several
      years with the abolition of SST and of the use of premedication before the
      application of antivenom sera, we used a similar schedule for ERIG application.
      Of the 1489 victims of animal bites, 1054 (71%) received ERIG; no patient was
      submitted to SST and all received intravenously anti-histamines (anti-H1 + anti
      H2) and corticosteroids before the procedure. The patients were kept under
      observation for 60 to 180 minutes and no adverse reaction was observed. On the
      basis of these results, since December 1995 ERIG application has been
      decentralized in Ribeirao Preto and has become the responsibility of the
      Emergency Unit of the University Hospital and the Central Basic Health Unit,
      where the same routine is used. Since then, 4216 patients have received ERIG
      (1818 at the Basic Health Unit and 2398 at the EU-UHFMRP), with no problems. The
      ideal would be the routine use of human rabies immune globulin (HRIG) in public
      health programs, but this is problematic, because of their high cost. However,
      while this does not occur, the use of SST is no longer justified at the time of
      application of ERIG, in view of the clinical evidence of low predictive value and
      low sensitivity of SST involving the application of heterologous sera. It is very
      important to point out that a negative SST result may lead the health team to a
      feeling of false safety that no adverse reaction will occur, but this is not true
      for the anaphylactoid reactions. The decision to use premedication, which is
      based on knowledge about anaphylaxis and on the pharmacology of the medication
      used, is left to the judgment of health professionals, who should always be
      prepared for eventual untoward events.

PMID- 11246286
TI  - Borna disease virus and psychiatry.
AB  - Borna disease virus (BDV), a noncytolytic neurotropic nonsegmented negative
      stranded RNA virus with a wide geographic distribution, infects several
      vertebrate animal species and causes an immune-mediated central nervous system
      (CNS) disease with various manifestations, depending on both host and viral
      factors. In animal infections, BDV can persist in the CNS and induce alterations
      in brain cell functions, neurodevelopmental abnormalities and behavioral
      disturbances. An association between BDV and psychiatric disorders (essentially
      schizophrenia and affective disorders) has been suggested by some serologic and
      molecular studies but further investigations are required to substantiate the
      possible contribution of this virus to the pathogenesis of these disorders.

PMID- 11246285
TI  - First isolation of dengue 3 in Brazil from an imported case.
AB  - The authors report the isolation of dengue 3 virus for the first time in Brazil.
      The patient, resident in Limeira-SP, traveled to Nicaragua on May 16th, 1998,
      where he stayed for two months. Starting on August 14 th he had fever, headache,
      myalgia, arthralgia, retro-orbital pain and diarrhea. He returned to Brazil on
      August 16th and was hospitalized in the next day. The patient had full recovery
      and was discharged on August 20th. The virus was isolated in C6/36 cell culture
      inoculated with serum collected on the 6th day after the onset of the symptoms.
      The serotype 3 was identified by indirect immunofluorescence assays performed
      with type-specific monoclonal antibodies. This serotype was further confirmed by
      polymerase chain reaction analysis. The introduction of a new dengue serotype in
      a susceptible population is a real threat for the occurrence of severe forms of
      the disease. The isolation and identification of dengue virus are important in
      order to monitoring the serotypes circulating in Brazil and to take the measures
      necessary to prevent and control an epidemic.

PMID- 11246287
TI  - Familial factors influencing the consumption of anxiolytics and hypnotics by
      children and adolescents.
AB  - Many hypotheses have been made to explain the high rate of benzodiazepine
      consumption in France, including a general cultural and/or familial tendency to
      use certain types of psychotropic drugs. This study explored the association
      between lifetime medication use by parents and their children. Two hundred and
      twenty-one young patients (158 boys and 63 girls) consulting at a child and
      adolescent psychiatry department, six to 16 years of age (mean = 9.7 years), were
      screened for lifetime use of psychotropic drugs using a structured interview.
      Parents were asked about their own consumption, as well as their children's.
      Lifetime consumption rates (at least once) were 22.2% in boys and 20.6% in girls,
      and 19.6% in children less than 11 years old. Higher rates were found in patients
      with emotional disorders (anxiety disorders and depression). In parents, 45.1% of
      mothers and 24.1% of fathers reported using medications at least once. A
      significant association was found between child and parental medication use:
      34.1% of children had positive lifetime consumption when their mothers also used
      medications at least once versus only 13.6% in other children (odds ratio = 3.31
      [1.68-6.50]; P = 0.001). The most significant association was found between
      medication use by girls and their mothers (odds ratio = 12.1 [2.38-61.5]; P =
      0.003). These data point to the existence of a family pattern of psychotropic
      drug consumption, especially in females.

PMID- 11246288
TI  - Family- and school-related stresses in depressed Hungarian children.
AB  - The aim of the study was 1) to identify recent and past life stresses as having a
      significant differential risk of childhood depression versus other childhood
      psychiatric illnesses, and 2) to establish if life stresses shared with other
      family members had a greater impact on the depression of the child than events of
      only personal relevance. Using a recently developed semi-structured interview
      (Diagnostic Evaluation Schedule for Children and Adolescents - Hungarian version,
      DESCA-H ), 68 life events of a total sample of 526 children were investigated.
      Two hundred and fifteen depressed preadolescents (mean age 12.73 years, SD 2.58)
      were compared with identical variables of 311 nondepressed mixed clinical
      controls (mean age: 10.91 years, SD 2.46) referred to child psychiatry care with
      other psychiatric symptomatology than depression. The life event questionnaire
      part of the DESCA-H was administered separately by means of lists of recent
      (within 1 year) and past stresses (events prior to 1 year before the assessment).
      With the two series of life stresses, two separate logistic regression analyses
      were performed. Of past stressors, physical punishment of the child by teachers,
      serious financial problems of the family and mental health problems of family
      members were found to be significant predictors of depression. From the series of
      recent stresses, moving to a new school, somatic illness, death of relatives and
      mental health disorders of family members were proved to be independent risk
      factors of depression for the children. The findings suggest that significant
      stresses of the child shared with other family members dominate in demarcating
      depressed children from nondepressed ones. School-related stresses are critically
      discussed.

PMID- 11246289
TI  - What becomes of children hospitalized for enuresis? Results of a catch-up study.
AB  - BACKGROUND: . The purpose of this study was to reassess former child and
      adolescent psychiatric patients with nocturnal enuresis as young adults and to
      compare them with former patients without enuretic symptoms and with a comparison
      group from the general population. METHOD: We used a 'catch-up' design. From a
      former child and adolescent psychiatric patient cohort we identified all subjects
      with documented enuretic symptoms in childhood and compared them with two groups
      matched for gender and age - non-enuretic patients and a comparison group from
      the general population. Subjects were assessed as adults with standardized
      instruments according to the criteria of ICD-10 (SCAN, IPDE) and dimensional
      values for depression, satisfaction with life, global functioning and personality
      (NEO-FFI). RESULTS: We assessed 55 former patients with nocturnal enuresis
      (recruitment rate 68%) after a mean interval of 13.1 years. At catch-up the
      former enuretic patients had a lower frequency of personality disorders (ICD-10),
      lower mean depression values, higher global functioning and a lower rate of
      psychiatric treatment after the age of 18 years than did former non-enuretic
      patients. Former enuretic patients did not differ significantly from the
      comparison group from the general population concerning any of the outcome
      variables, although there was a non-significant trend for former enuretic
      patients to more often fulfill criteria for a psychiatric ICD-10 diagnosis at
      catch-up. There were no differences concerning personality among the three groups
      at catch-up. CONCLUSION: Although it may constitute a mild vulnerability factor
      for further development, nocturnal enuresis had a good long-term outcome in a
      cohort of treated subjects.

PMID- 11246291
TI  - The structured interview for anorexic and bulimic disorders for DSM-IV and ICD-10
      (SIAB-EX): reliability and validity.
AB  - OBJECTIVE: For reliable and valid assessment and diagnostic categorization of
      eating disorders, self-report measures have considerable limitations. A semi
      structured interview - the SIAB-EX - was developed for a more reliable and valid
      assessment of eating disorders. METHODS: One study (videotapes of 31 inpatients,
      seven raters) was made to establish inter-rater reliability; in another study
      with 80 patients the SIAB-EX was compared to another semi-structured interview
      designed for comparable purposes (EDE). In a third study data was obtained on 377
      eating disorder patients seeking treatment to explore discriminant and convergent
      (construct) validity using the following self-rating scales: EDI, TFEQ, SCL-90,
      BDI, and the PERI Demoralization Scale. RESULTS: Inter-rater reliability of
      dichotomous ratings was good with mean kappa values of.81 (current) and.85
      (past). Comparison of the SIAB-EX with the EDE generally showed quite similar
      results and higher intercorrelation of the total scale (.77). There are, however,
      a number of differences between the two scales, which are discussed in detail.
      Construct validity of the SIAB-EX was established. CONCLUSION: Inter-rater
      reliability was good. Convergent and discriminant (construct) validity of the
      SIAB-EX was demonstrated. The constructs assessed by the SIAB and its subscales
      and items are discussed in the context of their correlations with other well
      known scales.

PMID- 11246290
TI  - Depressive symptoms as measured by the CDI in a population of northern Italian
      children.
AB  - The aim of this study was to evaluate some Children's Depression Inventory (CDI)
      psychometric properties and the prevalence of depressive symptoms in an
      unselected Italian sample of two hundred and eighty-four children aged 8 years.
      The CDI internal consistency was adequate (Cronbach's alpha:.80). The mean and
      standard deviation of CDI and the percentage of children at risk of depression
      (10.6%) in this sample are consistent with the figures reported by other studies
      carried out in northern Europe and North America. There were differences in
      gender and socioeconomic level in that boys scored higher than girls, and in the
      lower socioeconomic level there were more children at risk of depression. Ten
      items best discriminated children at risk for depression with 94% of correct
      classification. Most of these items consisted of observable signs. It is
      suggested that the CDI has noteworthy consistency across samples of relatively
      different cultures, that it can reliably be employed in the assessment of young
      children, and that observable signs outnumber internalizing symptoms of
      depression among children at risk

PMID- 11246293
TI  - Long-term treatment of chronic schizophrenia with risperidone: a study with
      plasma levels.
AB  - Twenty-four chronic schizophrenic outpatients with a mean age of 37.21 years +/-
      9.96 SD were treated with risperidone (RSP) at the dosage of 2-9 mg/die (mean
      4.46 mg/die +/- 1.30 SD, mean 0.06 mg/kg +/- 0.01 SD) for a year. Clinical
      evaluation was assessed with the Brief Psychiatric Rating Scale (BPRS), Positive
      and Negative Symptoms Scale (PANSS), Extrapyramidal Side Effects Rating Scale
      (EPSE) and a checklist for Anticholinergic Side Effects (ACS) at T0, then after 1
      (T1), 2 (T2), 3 (T3), 6 (T6), 9 (T9) and 12 (T12) months. RSP and 9-hydroxy
      risperidone (9OH-RSP) plasma levels were determined at T12 by the HPLC method.
      BPRS and PANSS mean values showed a significant improvement during the study. No
      correlation between RSP dosage (mg/kg) and RSP, 9OH-RSP plasma levels or active
      moiety resulted. A positive correlation between age and active moiety was
      observed. A positive correlation between RSP and 9OH-RSP plasma levels was
      observed. A curvilinear relationship between active moiety and PANSS improvement
      (%) was observed. Patients with the higher PANSS amelioration showed RSP + 9OH
      RSP plasma levels ranging from 15 to 30 ng/mL. RSP seems to be quite an effective
      drug. It seems, however, difficult to devise appropriate dose schedules and
      plasma level determination seems to be necessary in some cases.

PMID- 11246292
TI  - Associations of past conduct disorder with personality disorders in 'non
      psychotic' psychiatric inpatients.
AB  - The aim was to investigate associations of a history of features of DSM-III-R
      conduct disorder (CD) with features of DSM-III-R personality disorders (PDs) and
      psychopathy, in inpatient psychiatric practice. Fifty-six psychiatric inpatients,
      without a history of specified 'psychoses', were assessed by the SCID structured
      interview for DSM-III-R PDs and the 'Psychopathy Checklist Revised' (PCL-R). In a
      sample in which 59% had borderline PD, significant associations between a history
      of CD criteria and the adult features of antisocial PD (APD) were relatively
      specific compared with other PDs, but were weaker in women. However, significant
      correlations between the number of positive CD criteria and PCL-R scores were
      similar in both genders. The relatively specific associations between CD and
      adult features of APD are likely to be relevant to psychiatric patients who show
      various presentations of PD, if these include some adult features of APD. The
      findings inform the understanding of the development and classification of PDs.

PMID- 11246294
TI  - Childhood sexual abuse. An evaluation of a two-year group therapy in adult women.
AB  - Twenty-two female psychiatric outpatients with experiences of childhood sexual
      abuse took part in a two-year group therapy. All completed therapy. At the end of
      therapy the women's psychiatric symptoms were reduced and their social
      interaction and adjustment were improved. They evaluated relationships to their
      children, partners and friends to be improved.

PMID- 11246295
TI  - Pain modulation role of melatonin in eating disorders.
AB  - The objective of this study was to test the effect of melatonin on thermal pain
      threshold in female patients with eating disorders. Fourteen patients were
      included in the study. We found a parabolic relation between pain threshold and
      the content of urine sulfatoxymelatonin (r = 0.6299, P < 0.05). We can speculate
      that increase in severity of eating disorder pathology may decrease both the
      melatonin level and pain sensitivity. In contrast with expected melatonin
      analgesic effect, our results showed its possible normalizing influence as well
      on pathologically decreased pain sensitivity.

PMID- 11246296
TI  - Affective symptomatology in schizophrenia: a risk factor for tardive dyskinesia?
AB  - Affective symptomatology has repeatedly been suggested to confer susceptibility
      to tardive dyskinesia (TD). In our sample of 174 schizophrenic patients a history
      of depressive symptoms was not associated with the occurrence of TD, whereas
      manic symptomatology was significantly associated with the absence of TD. Thus,
      our data suggest that affective symptomatology cannot unambiguously be considered
      to predispose to TD.

PMID- 11246297
TI  - Verbal perseveration after right-unilateral ECT.
AB  - After electroconvulsive therapy (ECT), many patients experience a decrement in
      their mnestic capacity. We studied episodic memory in eight severely depressed
      patients treated with a course of right-unilateral ECT. For this purpose, a
      testing instrument was constructed by the authors. It was made of paper cards
      that held four pieces of information, namely a word, a number, a figure, and the
      color of the card. One of the cards was presented to the patients and the
      respective information was asked for on the subsequent day. Patients were tested
      every morning during the first two weeks of the ECT course. About half of the
      responses were correct. Patients did best in recalling the color; they did worst
      in recalling the number. Seven of the patients showed verbal perseverations. This
      is in accordance with the literature on perseveration in patients with neurologic
      deficits, especially in proactive-inhibitory tasks. Perseveration may be
      attributed to a deficit in selective attention, producing an arousal of
      irrelevant cues.

PMID- 11246298
TI  - Is a low transfusion threshold safe in critically ill patients with
      cardiovascular diseases?
AB  - OBJECTIVE: To compare a restrictive red blood cell transfusion strategy with a
      more liberal strategy in volume-resuscitated critically ill patients with
      cardiovascular disease. SETTING: Twenty-two academic and three community critical
      care units across Canada. STUDY DESIGN: Randomized controlled clinical trial.
      STUDY POPULATION: Three hundred fifty-seven critically ill patients with
      cardiovascular diseases from the Transfusion Requirements in Critical Care trial
      who had a hemoglobin concentration of <90 g/L within 72 hrs of admission to the
      intensive care unit. INTERVENTIONS: Patients were randomized to a restrictive
      strategy to receive allogeneic red blood cell transfusions at a hemoglobin
      concentration of 70 g/L (and maintained between 70 and 90 g/L) or a liberal
      strategy to receive red blood cells at 100 g/L (and maintained between 100 and
      120 g/L). RESULTS: Baseline characteristics in the restrictive (n = 160) and the
      liberal group (n = 197) were comparable, except for the use of cardiac and
      anesthetic drugs (p <.02). Average hemoglobin concentrations (85 +/- 6.2 vs. 103
      +/- 6.7 g/L; p <.01) and red blood cell units transfused (2.4 +/- 4.1 vs. 5.2 +/-
      5.0 red blood cell units; p <.01) were significantly lower in the restrictive
      compared with the liberal group. Overall, all mortality rates were similar in
      both study groups, including 30-day (23% vs. 23%; p = 1.00), 60-day, hospital,
      and intensive care unit rates. Changes in multiple organ dysfunction from
      baseline scores were significantly less in the restrictive transfusion group
      overall (0.2 +/- 4.2 vs. 1.3 +/- 4.4; p =.02). In the 257 patients with severe
      ischemic heart disease, there were no statistically significant differences in
      all survival measures, but this is the only subgroup where the restrictive group
      had lower but nonsignificant absolute survival rates compared with the patients
      in the liberal group. CONCLUSION: A restrictive red blood cell transfusion
      strategy generally appears to be safe in most critically ill patients with
      cardiovascular disease, with the possible exception of patients with acute
      myocardial infarcts and unstable angina.

PMID- 11246299
TI  - Variability among institutional review boards' decisions within the context of a
      multicenter trial.
AB  - BACKGROUND: Institutional review boards (IRBs) are given discretion to interpret
      and apply the federal regulations governing the protection of human subjects in
      research. OBJECTIVE: To determine the extent of the variability among different
      IRBs on their approved research practices and informed consent forms within the
      context of a multicenter trial that used a common protocol. DESIGN: Descriptive
      analysis of survey information and informed consent forms. SETTING AND
      PARTICIPANTS: Sixteen IRBs from the institutions participating in a multicenter
      trial comparing lower vs. traditional tidal volume ventilation in patients with
      acute lung injury. MEASUREMENTS: Analysis of survey information on IRBs' approved
      research practices. Analysis of informed consent forms for the presence and the
      adequacy of description of each basic element of informed consent specified in
      the federal regulations. Reading levels of informed consent forms. MAIN RESULTS:
      Surveys and IRB-approved consent forms were obtained from all of the contacted
      IRBs (n = 16). Variability was observed among several of the research practices;
      one IRB waived the requirement for informed consent, five IRBs permitted
      telephone consent, and three IRBs allowed prisoners to be enrolled. Three consent
      forms contained all of the basic elements of informed consent outlined in the
      federal regulations, and 13 forms had varying numbers of these elements absent
      (six forms without one element, four without two, one without three, and two
      without four). Reading levels of the consent forms ranged from grades 8.2 to 13.4
      (mean +/- sd was 11.6 +/- 1.2 grade level). CONCLUSIONS: Within a multicenter
      trial, IRBs reviewing a common protocol varied in several of their approved
      research practices and in the extent to which the basic elements of informed
      consent were included in their consent forms.

PMID- 11246300
TI  - Early postoperative enteral nutrition improves gut oxygenation and reduces costs
      compared with total parenteral nutrition.
AB  - OBJECTIVE: To evaluate the potential clinical, metabolic, and economic advantages
      of enteral nutrition over total parenteral nutrition. DESIGN: Prospective,
      randomized clinical trial. SETTING: Department of surgery in a university
      hospital. PATIENTS: Two hundred and fifty-seven patients with cancer of the
      stomach (n = 121), pancreas (n = 110), or esophagus (n = 26) were randomized to
      receive postoperative total parenteral nutrition (TPN group, n = 131) or early
      enteral nutrition (EEN group, n = 126). The nutritional goal was 25 kcal/kg/day.
      The two nutritional formulas were isocaloric and isonitrogenous, and they were
      continued until oral intake was at least 800 kcal/day. MEASUREMENTS: Morbidity,
      mortality, length of hospital stay, and treatment costs were evaluated in all
      patients. In 40 consecutive patients, selected nutritional, immunologic and
      inflammatory variables were studied. Moreover, intestinal oxygen tension was
      evaluated by micropolarographic implantable probes. MAIN RESULTS: The nutritional
      goal was reached in 100/126 (79.3%) patients in the EEN group and in 128/131
      (97.7%) patients in the TPN group (p <.001). In the EEN group, hyperglycemia
      (serum glucose, >200 mg/dL) was observed in 4.7% of the patients vs. 9.1% in the
      TPN group (p = NS). Alteration of serum electrolyte levels was 3.9% in the EEN
      group vs. 13.7% in the TPN group (p <.01). No significant difference was found in
      nutritional, immunologic, and inflammatory variables between the two groups. The
      overall complication rate was similar (40.4% for TPN vs. 35.7%, for EEN; p =.52).
      No difference was detected for either infectious or noninfectious complications,
      length of hospital stay, and mortality. From postoperative day 5, intestinal
      oxygen tension recovered faster in the EEN group than in the TPN group (43 +/- 5
      mm Hg vs. 31 +/- 4 mm Hg at day 7; p <.001). EEN was four-fold less expensive
      than TPN ($25 vs. $90.60/day, respectively). CONCLUSION: EEN represents a
      rational alternative to TPN in patients who undergo upper gastrointestinal tract
      surgery for cancer and who clinically require postoperative artificial nutrition.

PMID- 11246301
TI  - Bronchoscopy with bronchoalveolar lavage via the laryngeal mask airway in high
      risk hypoxemic immunosuppressed patients.
AB  - OBJECTIVE: Fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL) are
      major tools in the diagnosis of pulmonary complications in immunocompromised
      patients. Nevertheless, severe hypoxemia is an accepted contraindication to FOB
      in nonintubated patients. The purpose of this study was to evaluate the
      feasibility and safety of laryngeal mask airway (LMA)-supported FOB with BAL in
      immunosuppressed patients with suspected pneumonia and severe hypoxemia. DESIGN:
      Prospective, clinical investigation. SETTING: Medical intensive care unit of a
      university hospital. PATIENTS: Forty-six immunosuppressed patients admitted to
      our intensive care unit with suspected pneumonia and Pao2/Fio2 < or = 125.
      INTERVENTIONS: After the administration of 0.3 mg x kg(-1) of etomidate, the
      patients were ventilated manually while receiving 1.0 Fio2. After the
      administration of 2.5 mg x kg(-1) of propofol, followed by an infusion of 9.1 +/-
      2.3 mg x kg(-1) x hr(-1) of propofol, the LMA (size 3 or 4) was placed and
      connected to a bag-valve unit to allow manual ventilation with 1.0 Fio2. The FOB
      was introduced through a T-adapter attached to the LMA, and BAL was carried out
      with 150 mL of sterile 0.9% saline solution by sequential instillation and
      aspiration of 50-mL aliquots. MEASUREMENTS AND MAIN RESULTS: Three patients
      developed transient laryngospasm during passage of the bronchoscope via the LMA,
      which resolved with deepening of anesthesia. Changes in mean blood pressure,
      heart rate, Pao2/Fio2, and Paco2 values induced by the procedure did not reach
      significance. Seven patients (15%) presented hypotension (mean blood pressure,
      <60 mm Hg) maintained for 120 +/- 40 secs, which required plasma expanders in
      three cases. Oxygen desaturation to <90% occurred in six patients (13%) during
      BAL. Nevertheless, the lowest Sao2 during the procedure was significantly higher
      than the initial Sao2 (94% +/- 4% vs. 90% +/- 2%). No patient required tracheal
      intubation during the 8 hrs after the procedure. BAL had an overall diagnostic
      yield of 65%. Because of the results obtained by using the BAL analysis,
      treatment was modified in 33 (72%) cases. CONCLUSION: Application of the LMA
      appears to be a safe and effective alternative to intubation for accomplishing
      FOB with BAL in immunosuppressed patients with suspected pneumonia and severe
      hypoxemia.

PMID- 11246302
TI  - The hepatosplanchnic area is not a common source of lactate in patients with
      severe sepsis.
AB  - OBJECTIVE: To investigate the role of the splanchnic region in the
      hyperlactatemia of septic patients. DESIGN: Prospective, observational study.
      SETTING: Thirty-one-bed mixed medicosurgical intensive care unit. PATIENTS:
      Ninety invasively monitored and mechanically ventilated patients with severe
      sepsis. MEASUREMENTS AND MAIN RESULTS: Splanchnic lactate balance was measured in
      all patients. Splanchnic blood flow was determined by using the primed continuous
      indocyanine green infusion technique in 69 patients. In 71 patients, gastric
      mucosal Pco2 and the Pco2 gap (the difference between gastric and arterial Pco2)
      also were determined by using gas tonometry with an automated gas analyzer. In
      each patient, arterial, mixed-venous, and hepatic venous blood samples were
      obtained to determine hemoglobin oxygen saturations and lactate concentrations.
      Arterial and hepatic venous lactate concentrations were determined in triplicate
      and were averaged, and the arterial hepatic venous difference in lactate and
      lactate consumption were calculated. The splanchnic region produced lactate in
      only six of the 90 patients. Mean arterial pressure, cardiac index, arterial
      lactate, hepatic venous oxygen saturation, and catecholamine use were similar in
      the six patients with splanchnic lactate production and in the 84 others. The
      arterial hepatic venous differences in lactate and splanchnic lactate consumption
      were related directly to arterial lactate concentrations (y = 0.073x + 0.209,
      r(2) =.06, p <.05, and y = 0.06x + 0.183, r(2) =.08, p <.05, respectively) but
      were not related to Pco2 gap, to the gradient between mixed-venous and hepatic
      venous oxygen saturations, or to bilirubin concentrations. CONCLUSIONS:
      Splanchnic lactate release is uncommon in septic patients, even when
      hyperlactatemia is severe.

PMID- 11246303
TI  - Tissue factor pathway inhibitor response does not correlate with tissue factor
      induced disseminated intravascular coagulation and multiple organ dysfunction
      syndrome in trauma patients.
AB  - OBJECTIVE: To determine the precise relationship between tissue factor and tissue
      factor pathway inhibitor (TFPI) after trauma, as well as to test the hypothesis
      that low TFPI levels are not sufficient to prevent tissue factor-dependent
      intravascular coagulation, leading to multiple organ dysfunction syndrome (MODS).
      DESIGN: Prospective, observational cohort study. SETTING: Emergency room and
      intensive care unit in a university hospital. PATIENTS: Thirty-three trauma
      patients, 18 with disseminated intravascular coagulation (DIC) and 15 without DIC
      were studied. Ten normal, healthy volunteers served as control subjects.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Antigen concentration of
      tissue factor and TFPI, and global parameters of coagulation and fibrinolysis
      were measured on the day of admission, and on days 1-4 after admission. The
      number of systemic inflammatory response syndrome (SIRS) criteria that patients
      met and the DIC score were determined, simultaneously. The results of these
      measurements, incidence of MODS, and outcome were compared between the DIC
      patients and those without DIC. In the DIC patients, significantly higher tissue
      factor levels (p =.0049) and lower platelet counts (p =.0016) were found compared
      with the non-DIC patients and control subjects. However, the TFPI values remained
      at normal levels during the study period. No correlation was found between the
      peak levels of tissue factor and TFPI. The mean duration of SIRS and the maximum
      number of the SIRS criteria being met by the patients in the DIC group were
      statistically longer and higher than those in the non-DIC patients. The incidence
      of MODS and the number of the dysfunctioning organs were higher in the DIC
      patients compared with those in the non-DIC patients, and the DIC patients had a
      poor outcome. CONCLUSIONS: We systematically elucidated the relationship between
      tissue factor and TFPI in post-trauma patients. Highly activated tissue factor
      dependent coagulation pathway is not sufficiently prevented by the normal TFPI
      levels in patients with DIC. The DIC associated with thrombotic and inflammatory
      responses causes MODS, and leads to poor outcome in post-trauma patients.

PMID- 11246304
TI  - Plasma aluminum levels during sucralfate prophylaxis for stress ulceration in
      critically ill patients on continuous venovenous hemofiltration: a randomized,
      controlled trial.
AB  - OBJECTIVE: To investigate plasma aluminum levels in critically ill patients
      requiring continuous venovenous hemofiltration (CVVH), while receiving sucralfate
      for stress ulcer prophylaxis. DESIGN: Randomized, controlled study. SETTING:
      Cardiothoracic intensive care unit. PATIENTS: Twenty postoperative cardiac
      surgical patients INTERVENTIONS: Twenty patients requiring CVVH support for acute
      renal failure were randomized into two groups for concurrent stress ulcer
      prophylaxis. Group 1 (n = 10) received nasogastric sucralfate, and group 2
      patients received intravenous ranitidine. Plasma aluminum samples were analyzed
      at baseline and on days 1, 4, 8, and 14. MEASUREMENTS AND MAIN RESULTS: In both
      the sucralfate and ranitidine groups, clinical characteristics, number of days
      the patients were on CVVH support (median, 5.5 [range, 2-32] days, and median, 3
      [range, 2-18] days, respectively) and duration of prophylaxis (median, 12 [range,
      4-42] days, and median, 16 [range, 3-62] days, respectively) were similar. There
      were no significant differences in the baseline aluminum concentrations (median,
      0.37 [range, 0.15-1.63] micromol/L, vs. median, 0.32 [range, 0.11-1.0]
      micromol/L; p =.79). On initiation of therapy, aluminum levels in the sucralfate
      group increased dramatically on day 1 (median, 0.87 [range, 0.26-4.4] micromol/L)
      and peaked on day 4 (median, 2.84 [range, 1.52-4.44] micromol/L) with seven of
      the ten patients exhibiting levels of >2 micromol/L. In the ranitidine group,
      there were no significant elevations in aluminum levels above baseline. Analysis
      of the two groups at the four time points revealed that aluminum levels in the
      sucralfate group were up to 14 times higher, with the confidence intervals
      suggesting that the true value may be 2-27 times higher (p <.0001). On cessation
      of CVVH, a rapid decline in aluminum levels was observed. No clinical
      manifestations of these potentially toxic levels were observed. CONCLUSIONS: The
      use of sucralfate for stress ulcer prophylaxis in patients requiring CVVH results
      in toxic elevations in plasma aluminum levels. Alternative agents should be
      considered for prophylaxis in these patients.

PMID- 11246306
TI  - Self-reported symptom experience of critically ill cancer patients receiving
      intensive care.
AB  - OBJECTIVE: To characterize the symptom experience of a cohort of intensive care
      unit (ICU) patients at high risk for hospital death. DESIGN: Prospective analysis
      of patients with a present or past diagnosis of cancer who were consecutively
      admitted to a medical ICU during an 8-month period. SETTING: Academic, university
      affiliated, tertiary-care, urban medical center. PATIENTS: One hundred cancer
      patients treated in a medical ICU. INTERVENTION: Assessment of symptoms.
      MEASUREMENTS: Patients' self-reports of symptoms using the Edmonton Symptom
      Assessment Scale (ESAS), and ratings of pain or discomfort associated with ICU
      diagnostic/therapeutic procedures and of stress associated with conditions in the
      ICU. MAIN RESULTS: Hospital mortality for the group was 56%. Fifty patients had
      the capacity to respond to the ESAS, among whom 100% provided symptom reports.
      Between 55% and 75% of ESAS responders reported experiencing pain, discomfort,
      anxiety, sleep disturbance, or unsatisfied hunger or thirst that they rated as
      moderate or severe, whereas depression and dyspnea at these levels were reported
      by approximately 40% and 33% of responders, respectively. Significant pain,
      discomfort, or both were associated with common ICU procedures, but most
      procedure-related symptoms were controlled adequately for a majority of patients.
      Inability to communicate, sleep disruption, and limitations on visiting were
      particularly stressful among ICU conditions studied. CONCLUSIONS: Among
      critically ill cancer patients, multiple distressing symptoms were common in the
      ICU, often at significant levels of severity. Symptom assessment may suggest more
      effective strategies for symptom control and may direct decisions about
      appropriate use of ICU therapies.

PMID- 11246305
TI  - N-acetylcysteine reduces respiratory burst but augments neutrophil phagocytosis
      in intensive care unit patients.
AB  - OBJECTIVE: The antioxidant N-acetylcysteine (NAC) has been shown to attenuate
      septic tissue injury. To evaluate whether NAC affects host defense mechanisms in
      critically ill patients, thus predisposing to increased risk of infection, the
      current study focuses on neutrophil phagocytotic and burst activity after
      treatment with NAC. DESIGN: Prospective, randomized, clinical trial. SETTING:
      Twelve-bed operative intensive care unit in a university hospital. PATIENTS:
      Thirty patients diagnosed with sepsis/systemic inflammatory response syndrome, or
      multiple trauma. INTERVENTIONS: Patients were randomly assigned to receive either
      NAC (n = 15) for 4 days in increasing dosages (day 1: 6 g; day 2: 12 g; days 3
      and 4: 18 g) or a mucolytic basis dosage of NAC (3 x 300 mg/day [control]; n =
      15), respectively. MEASUREMENTS AND MAIN RESULTS: Blood samples were taken before
      NAC high-dose infusion (day 1), after increasing doses of NAC (days 3 and 5) and
      4 days after the last high-dose treatment (day 8). Neutrophil oxidative burst
      activity after stimulation with Escherichia coli and polymorphonuclear
      phagocytosis were determined in a flow cytometric assay. Baseline values of
      polymorphonuclear functions were comparable in both groups. NAC high-dose
      treatment resulted in a significantly improved phagocytosis activity compared
      with control patients. In contrast to this, polymorphonuclear burst activity was
      significantly reduced in the NAC high-dose treated group on day 3. CONCLUSION:
      These findings suggest that infusion of NAC in high doses affects granulocyte
      functions in critically ill patients. Antimicrobial host defense requires the
      effective sequence of cell adhesion, phagocytosis, and bactericidal respiratory
      burst. The enhanced phagocytotic activity might be a compensatory mechanism in
      states of impaired respiratory burst to maintain tissue sterility. For certain
      mechanisms of disease, the effects observed might be favorable (e.g.,
      ischemia/reperfusion, endothelial cell activation), for others (infection) this
      might be detrimental.

PMID- 11246307
TI  - Incidence of pressure ulcers in a neurologic intensive care unit.
AB  - OBJECTIVES: To determine the risk factors for pressure ulceration in an intensive
      care setting, to evaluate the Braden scale as a predictor of pressure ulcer risk
      in critically ill patients, and to determine whether pressure ulcers are likely
      to occur early in the hospital stay. DESIGN: Cohort study of patients with no
      preexisting ulcers with a 3-month enrollment period. SETTING: The neurologic
      intensive care unit and the neurologic intermediate unit at a primary
      care/referral hospital with a level I trauma center. PATIENTS: A total of 186
      patients entered the study. INTERVENTION: Within 12 hrs of admittance, initial
      assessment, photographs, and Braden score were completed. Patients were re
      examined every 4 days or at discharge from the unit, whichever came first. MAIN
      OUTCOME MEASURES: Determining risk factors for pressure ulcers, performing
      detailed statistical analyses, and testing the usefulness of the Braden score as
      a predictor of pressure ulcer risk. RESULTS: Twenty-three of 186 patients
      developed at least one pressure ulcer (incidence = 12.4%) after an average stay
      of 6.4 days. The Braden scale, which measures six characteristics of skin
      condition and patient status, proved to be a primary predictor of ulcer
      development. No ulcers developed in the 69 patients whose Braden score was 16 or
      higher. The likelihood of developing a pressure sore was predicted mathematically
      from the Braden score. However, being underweight was a significant and distinct
      factor in pressure ulcer development. CONCLUSIONS: Pressure ulcers may develop
      within the first week of hospitalization in the intensive care unit. Patients at
      risk have Braden scores of < or = 16 and are more likely to be underweight. These
      results suggest that aggressive preventive care should be focused on those
      patients with Braden scores of < or = 13 and/or a low body mass index at
      admission.

PMID- 11246308
TI  - Predicting hospital mortality for patients in the intensive care unit: a
      comparison of artificial neural networks with logistic regression models.
AB  - OBJECTIVE: Logistic regression (LR), commonly used for hospital mortality
      prediction, has limitations. Artificial neural networks (ANNs) have been proposed
      as an alternative. We compared the performance of these approaches by using
      stepwise reductions in sample size. DESIGN: Prospective cohort study. SETTING:
      Seven intensive care units (ICU) at one tertiary care center. PATIENTS: Patients
      were 1,647 ICU admissions for whom first-day Acute Physiology and Chronic Health
      Evaluation III variables were collected. INTERVENTIONS: None. MEASUREMENTS AND
      MAIN RESULTS: We constructed LR and ANN models on a random set of 1,200
      admissions (development set) and used the remaining 447 as the validation set. We
      repeated model construction on progressively smaller development sets (800, 400,
      and 200 admissions) and retested on the original validation set (n = 447). For
      each development set, we constructed models from two LR and two ANN
      architectures, organizing the independent variables differently. With the 1,200
      admission development set, all models had good fit and discrimination on the
      validation set, where fit was assessed by the Hosmer-Lemeshow C statistic (range,
      10.6-15.3; p > or = .05) and standardized mortality ratio (SMR) (range, 0.93 [95%
      confidence interval, 0.79-1.15] to 1.09 [95% confidence interval, 0.89-1.38]),
      and discrimination was assessed by the area under the receiver operating
      characteristic curve (range, 0.80-0.84). As development set sample size
      decreased, model performance on the validation set deteriorated rapidly, although
      the ANNs retained marginally better fit at 800 (best C statistic was 26.3 [p =
      .0009] and 13.1 [p = .11] for the LR and ANN models). Below 800, fit was poor
      with both approaches, with high C statistics (ranging from 22.8 [p <.004] to 633
      [p <.0001]) and highly biased SMRs (seven of the eight models below 800 had SMRs
      of <0.85, with an upper confidence interval of <1). Discrimination ranged from
      0.74 to 0.84 below 800. CONCLUSIONS: When sample size is adequate, LR and ANN
      models have similar performance. However, development sets of < or = 800 were
      generally inadequate. This is concerning, given typical sample sizes used for
      individual ICU mortality prediction.

PMID- 11246309
TI  - Effect of a collaborative weaning plan on patient outcome in the critical care
      setting.
AB  - OBJECTIVE: The process of weaning from mechanical ventilation can be complex,
      requiring collaborative care planning by members of the healthcare team. Improved
      outcomes have been demonstrated to result from collaborative decision-making
      processes (e.g., when ventilator teams were utilized). The purpose of this study
      was to evaluate the effect of a collaborative weaning plan (CWP) on length of
      time on mechanical ventilation, length of stay in the intensive care unit (ICU),
      and cost. DESIGN: A new, collaborative weaning plan in the form of a weaning
      board and flowsheet was introduced into a medical intensive care unit (MICU)
      setting. A pre- and post-quasi-experimental design using historical controls was
      used to test the hypotheses. Attempts to control for the effects of history were
      made by collecting data related to patient, staffing, and organizational
      variables that could independently effect outcome. SETTING: MICU in a west coast
      teaching hospital. PATIENTS: Critically ill patients receiving mechanical
      ventilation for 3 days or greater. INTERVENTION: Implementation of a
      collaborative weaning plan. MEASUREMENTS: Outcomes studied included length of
      stay in the MICU, length of time patients were mechanically ventilated in the
      MICU, cost per MICU stay, and the incidence of complications (e.g.,
      reventilation, readmission to the ICU, and mortality rate). MAIN RESULTS: The CWP
      decreased length of stay in the MICU by 3.6 days (p =.03) and length of
      ventilator time by 2.7 days (p =.06). There were no significant differences
      between groups related to cost or incidence of complications. CONCLUSIONS: These
      results support the usefulness of collaborative structures (such as weaning
      boards/flowsheets) in decreasing ICU length of stay.

PMID- 11246310
TI  - Risk factors for nosocomial pneumonia in critically ill trauma patients.
AB  - OBJECTIVE: To determine risk factors for nosocomial pneumonia in critically ill
      trauma patients. DESIGN: Prospective cohort study. SETTING: The trauma intensive
      care unit (ICU) of a 1500-bed tertiary-care hospital. PATIENTS: All critically
      ill trauma patients (n = 103) admitted consecutively between November 1995 and
      October 1996. INTERVENTIONS: A comparison of data recorded at the time of ICU
      admission and during the clinical evolution in patients with (n = 23) and without
      (n = 80) nosocomial pneumonia was made. Data referred mainly to possible risk
      factors were recorded; they also included factors related to pneumonia etiology
      and evolutive factors. Predictors of nosocomial pneumonia were assessed by
      logistic regression analysis. MEASUREMENTS AND MAIN RESULTS: The presence of
      significant growth on quantitative cultures of the protected specimen brush (> or
      = 103 colony forming units/mL) was required to accept pneumonia as
      microbiologically proven, as well as the concurrence of a cohort of clinical and
      radiologic signs. Twenty-three (22.3%) patients developed nosocomial pneumonia.
      The mean age of these patients was 41.7 yrs; 18 of them (78.3%) were men. The
      microorganisms isolated in significant concentrations were Acinetobacter baumanii
      (ten cases), Staphylococcus aureus (11 cases), Pseudomonas aeruginosa (five
      cases), Haemophilus influenzae (two cases), and Klebsiella pneumoniae,
      Citrobacter freundii, Serratia marcescens, Enterococcus spp., Enterobacter spp.,
      coagulase-negative Staphylococcus, and Streptococcus intermedius (one case each
      one). Risk factors for pneumonia by univariate analysis included nasogastric
      tube; continuous enteral feeding; prolonged mechanical ventilation (>1 day); use
      of H2-receptor antagonist, sucralfate, muscle relaxants, corticosteroids,
      barbiturates, and inotropic agents; positive end-expiratory pressure; intense
      sedation; re-intubation; tracheotomy; urgent brain computed tomography (CT) scan;
      craniotomy; iatrogenic event; and hyperventilation. The mortality rate was 43.5%
      (10 of 23) in the nosocomial pneumonia group and 18.8% in patients without
      nosocomial pneumonia (p =.02). Also, the mean stay in the ICU, the therapeutic
      charge (measured with total and mean punctuation of the Therapeutic Intervention
      Scoring System) and the complications, infectious and noninfectious, of the
      clinical evolution were significantly more frequent in patients with nosocomial
      pneumonia than in those without pneumonia (p <.05). In the multivariate analysis,
      continuous enteral feeding, craniotomy, prolonged mechanical ventilation (>24
      hrs), use of positive end-expiratory pressure, and corticotherapy were
      independent predictors of nosocomial pneumonia. CONCLUSIONS: It seems that
      factors related to the patient's clinical course, rather than variables
      registered on the first days of ICU admission, are those that would exert an
      influence on the development of nosocomial pneumonia in critically ill trauma
      patients. In this way, from our point of view, in our study the main risk factors
      are the use of prolonged mechanical ventilation (>4 hrs) and positive end
      expiratory pressure. At the same time, we can conclude that the reduction of this
      infection incidence could decrease the mean stay in the ICU, the therapeutic
      charge, and the prognosis in terms of mortality and morbidity.

PMID- 11246311
TI  - The hypothalamic-pituitary-adrenal axis of patients with severe sepsis: altered
      response to corticotropin-releasing hormone.
AB  - OBJECTIVE: To investigate the functional integrity of the hypothalamic-pituitary
      adrenal (HPA) axis in patients with severe sepsis by stimulating with
      corticotropin-releasing hormone (CRH). DESIGN: Prospective observational study in
      consecutive intensive care unit patients with severe sepsis. SETTING: Surgical
      intensive care unit and outpatient department of endocrinology in a university
      hospital. PATIENTS: The study included 20 patients with the diagnosis of severe
      sepsis; six critically ill, nonseptic patients after major surgery; ten patients
      with primary adrenal insufficiency; ten patients with anterior pituitary
      insufficiency; and ten individuals without clinical signs of HPA axis
      disturbance. INTERVENTIONS: CRH tests were performed with an intravenous bolus
      injection of 100 microg of human CRH. MEASUREMENTS AND MAIN RESULTS: We studied
      the functional integrity of the HPA axis in patients with severe sepsis by
      performing the CRH test. In addition, during the period of severe sepsis, we
      repeatedly measured basal plasma concentrations of adrenocorticotropin hormone
      (ACTH) and cortisol. The mean basal plasma cortisol concentration was decreased
      significantly in nonsurvivors with severe sepsis (288.8 +/- 29.1 [sem] nmol/L)
      compared with survivors (468.1+/- 18.6 nmol/L; p <.01). By calculating the
      ACTH/cortisol indices, we found no evidence for adrenal insufficiency in patients
      with severe sepsis. The mean ACTH/cortisol indices of nonsurvivors with severe
      sepsis (0.02 +/- 0.008) and survivors (0.01 +/- 0.002) were significantly lower
      compared with the index of patients with primary adrenal insufficiency (6.8 +/-
      1.0; p <.001). In contrast, in nonsurvivors with severe sepsis, the plasma
      cortisol response to CRH stimulation was impaired compared with survivors: The
      mean basal cortisol concentration within the CRH test was 269.4 +/- 39.8 nmol/L
      in nonsurvivors compared with 470.8 +/- 48.4 nmol/L in survivors and increased to
      a peak value of 421.6 +/- 72.6 nmol/L in nonsurvivors and 680.7 +/- 43.8 nmol/L
      in survivors (p <.02). However, the change in plasma cortisol, expressed as mean
      +/- sem and calculated by subtracting the basal cortisol from the peak cortisol
      after CRH stimulation, was not significantly different in survivors with severe
      sepsis (243.5 +/- 36.1, range 111.0-524.0 nmol/L, n = 15) compared with
      nonsurvivors (161.0 +/- 38.9, range 42.0-245.0 nmol/L, n = 5; p >.05).
      CONCLUSIONS: We found lower basal plasma cortisol concentrations in nonsurvivors
      compared with survivors of severe sepsis. In addition, the plasma cortisol
      response to a single CRH stimulation was impaired in nonsurvivors compared with
      survivors. Reduced responses to CRH stimulation may reflect a state of
      endocrinologic organ dysfunction in severe sepsis.

PMID- 11246313
TI  - Hyperprocalcitonemia in patients with perioperative myocardial infarction after
      cardiac surgery.
AB  - OBJECTIVE: To describe and compare procalcitonin (PCT) concentrations after
      cardiac surgery in uncomplicated patients and in patients with perioperative
      myocardial infarction (PMI). DESIGN: Retrospective comparative study. SETTING:
      One university hospital. PATIENTS: Fifty-eight adult patients undergoing cardiac
      surgery. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: In a first step,
      plasma PCT and C-reactive protein concentrations were measured preoperatively and
      until 72 hrs postoperatively in ten consecutive patients who underwent
      uncomplicated cardiac surgery. PCT concentrations increased progressively from
      the end of cardiopulmonary bypass (0.09 +/- 0.09 ng/mL), peaked at 24 hrs
      postoperatively (1.14 +/- 1.24 ng/mL), and began to decrease at 48 hrs. C
      reactive protein appeared to peak at 48 hrs (from 5.8 +/- 11.7 mg/L
      preoperatively to 265.1 +/- 103.5 mg/L on the second postoperative day). In a
      second step, PCT concentrations were measured at day one in 23 patients (PMI
      group) who presented high postoperative plasma cardiac troponin I concentrations
      and were compared with PCT concentrations observed in 25 matched uncomplicated
      patients. All patients were free from infection. PCT in the PMI group was
      significantly higher than in the control group (27.1 +/- 63.2 vs. 2.0 +/- 2.4
      ng/mL, respectively; p =.0053). CONCLUSION: Because high plasma concentrations of
      PCT were found in patients with PMI after cardiac surgery, it may be suggested
      that, in the early postoperative period, elevated plasma PCT concentrations
      should be interpreted with caution regarding infection diagnosis.

PMID- 11246312
TI  - Pharmacoeconomic assessment of propofol 2% used for prolonged sedation.
AB  - OBJECTIVE: To demonstrate that the use of propofol 2% is comparable to propofol
      1% in effectiveness and in the wake-up time used for prolonged sedation. DESIGN:
      Open-label, case cohort study with a cohort of historical controls, phase IV
      clinical trial. SETTING: Medical and surgical intensive care unit (ICU) in a
      community hospital. PATIENTS: Fifty-one consecutive patients (medical, surgical,
      and trauma) admitted to our ICU requiring mechanical ventilation for >24 hrs.
      METHODS: All patients received propofol 2% (1-6 mg.kg-1.hr-1, starting with the
      lowest dose) and morphine chloride (0.5 mg.kg-1.24 hrs-1). A 4-5 level of
      sedation (Ramsay scale) was recommended. When weaning was indicated clinically,
      sedation and analgesia were interrupted abruptly, mechanical ventilation was
      discontinued, and the patient was connected to a T-bridge. OUTCOME MEASUREMENTS:
      Inability to attain the desired level of sedation with the highest dose rate of
      proposal, and hypertriglyceridemia >500 mg/dL, were considered therapeutic
      failure. The time between discontinuation of mechanical ventilation and
      extubation was measured. Those variables, as well as different items related to
      ICU cost, were compared between the study group and two historical groups sedated
      with propofol 1% and midazolam. RESULTS: The duration of sedation was 122.4 +/-
      89.2 (sd) hrs for the propofol 2% group. The frequency of hypertriglyceridemia
      was 3.9% and 20.4% for the propofol 2% and the propofol 1% groups, respectively
      (p =.016). Therapeutic failure rates were 19.6% and 33.4% for the propofol 2% and
      propofol 1% groups, respectively (p =.127). The lower frequency of
      hypertriglyceridemia was associated with a higher number of patients reaching
      weaning. Weaning time was similar in the two propofol groups, 32.3 hrs ($1,744)
      for the propofol 2% group vs. 97.9 hrs ($5,287) for the midazolam group. Cost of
      sedation was $2.68 per hour for the midazolam group and $7.69 per hour for the
      propofol group. There was a favorable cost-benefit ratio for the propofol group,
      attributable to the shorter weaning time, although benefit was less than expected
      because higher doses of propofol 2% than propofol 1% were required during the
      first 48 hrs (p <.05). CONCLUSIONS: The new propofol 2% preparation is an
      effective sedative agent and is safe because of the low frequency of associated
      hypertriglyceridemia. The shorter weaning time associated with the use of
      propofol 2% as compared with midazolam compensates for its elevated cost. The
      economic benefit of propofol 2% is less than expected because higher doses of
      propofol 2% than propofol 1% are required over the first 48 hrs.

PMID- 11246314
TI  - Differential effects of clonidine, dopamine, dobutamine, and dopexamine on basal
      and acid-stimulated mucosal blood flow in the rat stomach.
AB  - OBJECTIVE: To analyze the effects of clonidine, dopamine, dobutamine, and
      dopexamine on gastric mucosal blood flow (GMBF) at baseline and after stimulation
      by acid back diffusion through a disrupted gastric mucosal barrier. DESIGN:
      Prospective, randomized, unblinded study. SETTING: University research
      laboratory. SUBJECTS: Adult Sprague-Dawley rats. INTERVENTIONS: Mean arterial
      blood pressure (MAP) and heart rate (HR) were recorded from a carotid artery of
      the phenobarbital-anesthetized animals. A jugular vein was cannulated for
      continuous infusion of saline and intravenous drug administration. The stomach
      was prepared for luminal perfusion and for recording GMBF with the hydrogen gas
      clearance technique. Gastric mucosal vascular conductance (GMVC) was calculated
      as GMBF divided by MAP. MEASUREMENTS AND MAIN RESULTS: Clonidine (37.5 and 112.5
      nmol x kg(-1)) lowered MAP and HR and caused gastric vasodilation as shown by a
      rise of GMVC. The 2.5-fold increase in GMVC elicited by gastric perfusion with
      HCl (0.15 M) plus ethanol (25%) was depressed by clonidine. All cardiovascular
      effects of clonidine were prevented by the alpha2-adrenoceptor antagonist
      idazoxan (2 micromol x kg(-1)). Infusion of dopamine (15 and 45 micromol x kg(-1)
      x hr(-1)), dobutamine, or dopexamine (each at 5 and 15 micromol x kg(-1) x hr(
      1)) caused tachycardia. GMVC at baseline was attenuated by the higher dose of
      dopamine and dopexamine, but not dobutamine. In contrast, the acid-induced
      vasodilation in the gastric mucosa was depressed by dobutamine and dopexamine,
      but not dopamine. CONCLUSIONS: Clonidine, dobutamine, and dopexamine at high
      dosage suppress the gastric mucosal vasodilator response to acid back diffusion,
      which is an important defense mechanism. Although the dose equivalence between
      rats and humans is not known, the antivasodilator effects highlight an adverse
      action whereby large doses of dobutamine, dopexamine, and clonidine may
      compromise gastric mucosal homeostasis and facilitate stress ulcer formation.
      Dopamine lacks this detrimental activity.

PMID- 11246315
TI  - Effect of NaHCO3 on cardiac energy metabolism and contractile function during
      hypoxemia.
AB  - OBJECTIVE: To examine the impact of administration of NaHCO3 on contractility and
      energy metabolism of the myocardium during hypoxemia. METHODS: Regional
      myocardial hypoxia was induced in the left anterior descending (LAD) artery
      myocardium in anesthetized, open-chest dogs, using a perfusion circuit between
      the right atrium and the LAD artery, and a membrane oxygenator. The rate of flow
      in LAD artery was maintained constant with the use of a roller pump. During
      hypoxia, eight dogs were administered isotonic NaHCO3 in the circuit and six
      other dogs received equimolar NaCl. Myocardial contractile function was assessed
      using sonomicrometry for measurement of percentage of systolic shortening and
      preload recruitable stroke work. Oxygen consumption and the rate of appearance of
      lactate were measured. Clamp-frozen tissue samples were obtained at the end of
      the experiment from the hypoxic LAD myocardium and the nonhypoxic circumflex
      myocardium for measurement of tissue lactate level. RESULTS: During hypoxia,
      there was a significant decrease in oxygen consumption by the LAD myocardium (35
      +/- 7 micromol/min in the NaCl group and 40 +/- 7 micromol/min in the NaHCO3
      group during hypoxia vs. 131 +/- 11 micromol/min during aerobic perfusion). There
      was also a significant decrease in myocardial contractility as measured by
      percentage of systolic shortening (14 +/- 3% to -8 +/- 3%); NaHCO3 infusion
      during hypoxia did not improve myocardial contractility (-7 +/- 2%). Similar
      results were obtained with measurements of preload recruitable stroke work. The
      rate of production of lactate during hypoxia was substantially lower than
      expected, based on the calculated oxygen deficit, and was not significantly
      increased by the administration of NaHCO3 (33 +/- 9 micromol/min in the NaCl
      group and 51 +/- 5 micromol/min in the NaHCO3 group). Tissue lactate was not
      statistically different in the hypoxic myocardium supplied by the LAD artery and
      the nonhypoxic myocardium supplied by the circumflex artery in either group.
      CONCLUSION: The response of the myocardium to hypoxia is to decrease its
      mechanical work and metabolic demand. The infusion of NaHCO3 did not enhance
      myocardial contractile function or flux in glycolysis during hypoxia. We
      speculate that this diminished mechanical work and metabolic demand may represent
      an adaptive response to preserve cellular integrity until oxygen delivery is
      restored.

PMID- 11246316
TI  - Beneficial effects of low-dose prostacyclin on cat intestinal perfusion during
      endotoxemia as evaluated with microdialysis and oxygen transport variables.
AB  - OBJECTIVE: To evaluate the effects of low-dose prostacyclin on intestinal
      perfusion during endotoxemia. DESIGN: A randomized, blinded experimental study.
      SETTING: A university laboratory. SUBJECTS: Sixteen anesthetized cats.
      INTERVENTIONS: The animals received endotoxin by continuous intravenous infusion
      (0.5 mg/kg plus 0.5 mg x kg(-1) x hr(-1)) and a continuous volume replacement
      throughout the experiment. Four hours after the start of endotoxin, the animals
      were randomized to receive an infusion of either prostacyclin at a dose of 1 ng x
      kg(-1) x min(-1) (prostacyclin group) or vehicle (control group) during the next
      4 hrs. MEASUREMENTS AND MAIN RESULTS: Intestinal vascular resistance was
      calculated from systemic arterial pressure, central venous pressure, and superior
      mesenteric artery blood flow, and intestinal oxygen delivery and uptake were
      calculated from superior mesenteric artery and vein blood samples and blood flow.
      Interstitial lactate, pyruvate, glucose, and glycerol in the ileal wall were
      measured by using microdialysis. There were no differences in baseline values
      between the groups. Systemic blood pressure decreased initially but recovered and
      remained stable in both groups. In the control group, intestinal vascular
      resistance increased from 10.9 +/- 1.0 to 24.7 +/- 5.3 mm Hg x mL x min(-1) x kg(
      1) (p <.05) at 8 hrs, and oxygen delivery decreased from 2.6 +/- 0.2 to 1.3 +/-
      0.3 mL x min(-1) x kg(-1) (p <.05). Simultaneously, microdialysis lactate
      increased from 1.6 +/- 0.1 to 3.6 +/- 0.5 mmol/L (p <.05) with concomitant
      pyruvate increase and unchanged lactate/pyruvate ratio. Blood lactate increased
      and pH decreased. In the prostacyclin group at 8 hrs, intestinal vascular
      resistance of 6.9 +/- 0.8 mm Hg x mL x min(-1) x kg(-1) was lower and intestinal
      oxygen delivery of 3.2 +/- 0.3 was higher (p <.05) than in the control group at 8
      hrs. Intestinal oxygen uptake of 0.54 +/- 0.10 mL x min(-1) x kg(-1) was higher
      than in the control group, in which oxygen uptake was 0.26 +/- 0.04 mL x min(-1)
      x kg(-1). Lactate, pyruvate, and pH were normalized at 8 hrs in the prostacyclin
      group. CONCLUSION: Low-dose prostacyclin has beneficial effects on small
      intestinal perfusion during endotoxemia in this experimental cat model.

PMID- 11246317
TI  - Inhibition of hypoxic pulmonary vasoconstriction by carbon monoxide in dogs.
AB  - OBJECTIVE: We tested the hypothesis that carbon monoxide might participate in the
      modulation of hypoxic pulmonary vasoconstriction (HPV) by prostacyclin (PGI2) and
      nitric oxide. DESIGN: Prospective, interventional study. SETTING: University
      laboratory. SUBJECTS: Nineteen intact anesthetized mongrel dogs. INTERVENTIONS:
      Right heart catheterization for the measurements of mean pulmonary artery
      pressure (Ppa), left atrial pressure estimated from occluded Ppa (Ppao),
      pulmonary capillary pressure (Pcp) calculated from the Ppa decay curve after
      balloon occlusion, and cardiac output (Q); inferior vena cava balloon for the
      control of Q by manipulation of venous return; ventilation in hyperoxia (fraction
      of inspired O2, 0.4) or in hypoxia (Fio2, 0.1); inhibition of cyclooxygenase by
      indomethacin (Indo); inhibition of nitric oxide synthase by NG-nitro-l-arginine
      (L-NA); inhibition of heme oxygenase by mesoporphyrin IX (SnMP); inhalation of
      nitric oxide (20 ppm); and inhalation of carbon monoxide (100 ppm). MEASUREMENTS
      AND MAIN RESULTS: The first seven dogs were weak responders to hypoxia as
      assessed by a hypoxia-induced increase in the gradient between Ppa and Ppao,
      measured at one level of Q kept constant, by an average of only 2 mm Hg (p = NS).
      This HPV was markedly increased by the combined administration of Indo and L-NA.
      A further enhancement of HPV was observed after the addition of SnMP, leading to
      severe pulmonary hypertension with an average increase in Ppa to 39 mm Hg.
      Inhaled nitric oxide inhibited HPV only after the combined administration of
      Indo, L-NA, and SnMP. Inhaled carbon monoxide had no effect. The next 12 dogs
      were stronger responders to hypoxia, as assessed by a hypoxia-induced increase in
      the gradient between Ppa and Ppao, measured at several levels of Q, by an average
      of 3 mm Hg (p <.05). This HPV was of the same magnitude after administration of
      placebo (n = 6) or SnMP (n = 6). Addition of Indo enhanced HPV to the same extent
      in the placebo and in the SnMP groups. Addition of L-NA induced a further
      enhancement of HPV, which was, however, greater in the SnMP group. There was a
      slight increase in the capillary-venous segment relative to the arterial segment
      in hypoxic conditions, but the partitioning of pulmonary vascular resistance was
      otherwise unaffected by nitric oxide, carbon monoxide, or PGI2. CONCLUSIONS:
      Endogenous carbon monoxide modulates canine HPV only in the absence of nitric
      oxide. The vasodilation mediated by nitric oxide, PGI2, or carbon monoxide is
      essentially distributed between proximal and distal sites proportionally to the
      degree of constriction produced during hypoxia.

PMID- 11246318
TI  - Effects of epinephrine on intestinal oxygen supply and mucosal tissue oxygen
      tension in pigs.
AB  - OBJECTIVE: To study the effects of increasing dosages of epinephrine given
      intravenously on intestinal oxygen supply and, in particular, mucosal tissue
      oxygen tension in an autoperfused, innervated jejunal segment. DESIGN:
      Prospective, randomized experimental study. SETTING: Animal research laboratory.
      SUBJECTS: Domestic pigs. INTERVENTIONS: Sixteen pigs were anesthetized,
      paralyzed, and normoventilated. A small segment of the jejunal mucosa was exposed
      by midline laparotomy and antimesenteric incision. Mucosal oxygen tension was
      measured by using Clark-type surface oxygen electrodes. Microvascular hemoglobin
      oxygen saturation and microvascular blood flow (perfusion units) were determined
      by tissue reflectance spectrophotometry and laser-Doppler velocimetry. Systemic
      hemodynamics, mesenteric-venous acid-base and blood gas variables, and systemic
      acid-base and blood gas variables were recorded. Measurements were performed
      after a resting period and at 20-min intervals during infusion of increasing
      dosages of epinephrine (n = 8; 0.01, 0.05, 0.1, 0.5, 1, and 2 microg x kg(-1) x
      min(-1)) or without treatment (n = 8). In addition, arterial and mesenteric
      venous lactate concentrations were measured at baseline and at 60 and 120 mins.
      MEASUREMENTS AND MAIN RESULTS: Epinephrine infusion led to significant
      tachycardia; an increase in cardiac output, systemic oxygen delivery, and oxygen
      consumption; and development of lactic acidosis. Epinephrine significantly
      increased jejunal microvascular blood flow (baseline, 267 +/- 39 perfusion units;
      maximum value, 443 +/- 35 perfusion units) and mucosal oxygen tension (baseline,
      36 +/- 2.0 torr [4.79 +/- 0.27 kPa]; maximum value, 48 +/- 2.8 torr [6.39 +/-
      0.37 kPa]) and increased hemoglobin oxygen saturation above baseline. Epinephrine
      increased mesenteric venous lactate concentration (baseline, 2.9 +/- 0.6 mmol x
      L(-1); maximum value, 5.5 +/- 0.2 mmol x L(-1)) without development of an
      arterial-mesenteric venous lactate concentration gradient. CONCLUSIONS:
      Epinephrine increased jejunal microvascular blood flow and mucosal tissue oxygen
      supply at moderate to high dosages. Lactic acidosis that develops during infusion
      of increasing dosages of epinephrine is not related to development of
      gastrointestinal hypoxia.

PMID- 11246319
TI  - Methylene blue reduces lung fluid filtration during the early phase of
      endotoxemia in awake sheep.
AB  - OBJECTIVE: To determine whether methylene blue (MB), an inhibitor of soluble
      guanylate cyclase and nitric oxide synthase, alters lung hemodynamics and fluid
      filtration after endotoxin in sheep. DESIGN: Prospective, randomized, controlled
      experimental study with repeated measurements. SETTING: University animal
      laboratory. SUBJECTS: Eight yearling, awake sheep. INTERVENTIONS: Sheep were
      instrumented for a chronic study with vascular and lung lymph catheters. In two
      experiments, separated by 1 wk of recovery, the animals received intravenously
      either an injection of MB 10 mg/kg or a corresponding volume of 0.9% sodium
      chloride as pretreatment. Thirty minutes later, sheep received a bolus injection
      of Escherichia coli endotoxin 1 microg/kg, followed by either an infusion of MB
      2.5 mg/kg/hr or a corresponding volume of 0.9% sodium chloride for 5 hrs.
      MEASUREMENTS AND MAIN RESULTS: MB decreased the early phase endotoxin-induced
      rises in pulmonary capillary pressure and pulmonary vascular resistance. MB also
      reduced the increments in lung lymph flow (QL) and protein clearance (CL) as well
      as the rightward shift of the permeability-surface area product (PS). In
      addition, MB diminished the decrease in cardiac output, stabilized mean arterial
      pressure, and precluded the rise in plasma and lung lymph cyclic guanosine 3'-5'
      monophosphate. However, during the late phase, MB-treated sheep presented with a
      faster rise in QL with no difference in CL and PS from the endotoxemic controls.
      CONCLUSIONS: During the early phase of endotoxemia in sheep, MB attenuates lung
      injury by decreasing the enhanced lung fluid filtration as a result of reduced
      pulmonary capillary pressure and permeability. However, MB does not counteract
      the late phase increase in lung fluid filtration.

PMID- 11246320
TI  - Dehydroepiandrosterone decreases mortality rate and improves cellular immune
      function during polymicrobial sepsis.
AB  - OBJECTIVE: Sepsis is associated with a marked depression of cellular immune
      function. The steroid hormone dehydroepiandrosterone (DHEA) is proposed to have
      immunoenhancing activities. We, therefore, investigated the effect of DHEA on the
      mortality rate and cellular immune functions in an experimental model of sepsis.
      DESIGN: Randomized animal study. SETTING: Level I trauma center, university
      research laboratory. SUBJECTS: Male NMRI mice. INTERVENTIONS: Mice were subjected
      to laparotomy (sham) or cecal ligation and puncture (CLP). Mice were treated with
      (sham/DHEA; CLP/DHEA) or without (sham; CLP) the steroid hormone DHEA (30 mg/kg
      sc). Animals were killed 48 hrs after the onset of sepsis. MEASUREMENTS AND MAIN
      RESULTS: The survival rate of septic mice was determined 24 and 48 hrs after
      onset of sepsis. Forty-eight hours after the septic challenge, a white blood cell
      count was performed and serum tumor necrosis factor (TNF)-alpha and interleukin
      (IL)-1beta concentrations were monitored using ELISA. Furthermore, the delayed
      type of hypersensitivity (DTH) reaction was evaluated on the basis of ear pinna
      swelling after dinitrofluorobenzene (DNFB) administration, and clinical variables
      (body weight, temperature, heart rate, fluid input/output, food intake) were
      monitored using metabolic cages. DHEA administration improved the survival rate
      (87% vs. 53% after 48 hrs; p <.001). This was accompanied by a restoration of the
      depressed DTH reaction and a reduction in TNF-alpha serum concentrations (20.7 +/
      1.4 pg/mL vs. 32.4 +/- 6.6 pg/mL). CONCLUSIONS: These results demonstrate that
      DHEA administration leads to an increased survival following a septic challenge.
      The immunoenhancing effect of DHEA is accompanied by a reduction of TNF-alpha
      release and an improved activity of T-cellular immunity. DHEA administration may,
      therefore, be beneficial in systemic inflammation.

PMID- 11246321
TI  - Impaired target site penetration of beta-lactams may account for therapeutic
      failure in patients with septic shock.
AB  - OBJECTIVE: Current guidelines for adjusting antimicrobial therapy regimens
      commonly are based on drug concentrations measured in plasma. In septic patients,
      however, the interstitial space of soft tissues in addition to the central
      compartment represents the target site of infection. We thus hypothesized that
      one explanation for therapeutic failure during antibiotic treatment might be the
      inability to achieve effective antimicrobial concentrations in the interstitial
      space fluid of soft tissues. This is corroborated by the fact that piperacillin,
      a frequently administered beta-lactam antibiotic, often fails to be effective
      despite documented susceptibility of the causative pathogen in vitro. DESIGN:
      Prospective comparative study of two groups. SETTING: The intensive care unit and
      research ward of an university hospital. SUBJECTS: Six patients with septic shock
      and a control group of six gender- and age-matched healthy volunteers.
      INTERVENTIONS: To measure piperacillin penetration into the interstitial space
      fluid of skeletal muscle and subcutaneous adipose tissue, we employed
      microdialysis after a single intravenous administration of 4.0 g of piperacillin
      to patients and healthy volunteers. Piperacillin concentrations were assayed by
      using reversed-phase high-pressure liquid chromatography. MEASUREMENTS AND MAIN
      RESULTS: In septic shock patients, interstitial piperacillin concentrations in
      skeletal muscle and subcutaneous adipose tissue were five- to ten-fold lower than
      corresponding free plasma concentrations (p <.03). Mean piperacillin
      concentrations in subcutaneous adipose tissue never exceeded 11 microg/mL, which
      is below the minimal inhibitory concentration for a range of relevant pathogens
      in patients with septic shock. CONCLUSION: The results of the present study
      demonstrate that in septic shock patients, piperacillin concentrations in the
      interstitial space may be subinhibitory, even though effective concentrations are
      attained in plasma. The lack of success of antimicrobial therapy in these
      patients thus might be attributable to inadequate target site penetration of
      antibiotics.

PMID- 11246322
TI  - Protective effects of low tidal volume ventilation in a rabbit model of
      Pseudomonas aeruginosa-induced acute lung injury.
AB  - OBJECTIVE: To determine whether low "stretch" mechanical ventilation protects
      animals from clinical sepsis after direct acute lung injury with Pseudomonas
      aeruginosa as compared with high "stretch" ventilation. DESIGN: Prospective
      study. SETTING: Experimental animal laboratory. SUBJECTS: Twenty-seven
      anesthetized and paralyzed rabbits. INTERVENTIONS: P. aeruginosa (109 colony
      forming units) was instilled into the right lungs of rabbits that were then
      ventilated at a tidal volume of either 15 mL/kg (n = 11) or 6 mL/kg (n = 7) for 8
      hrs. Control animals were ventilated at a tidal volume of either 15 mL/kg (n = 4)
      or 6 mL/kg (n = 5) for 8 hrs, but an instillate without bacteria was used. A
      positive end-expiratory pressure of 3-5 cm H2O was used for all experiments.
      Radiolabeled albumin was used as a marker of alveolar epithelial permeability.
      MEASUREMENTS AND MAIN RESULTS: Hemodynamics, arterial blood gas determination,
      alveolar permeability, wet-to-dry ratios on lungs, and time course of bacteremia
      were determined. When final values were compared with the values at the beginning
      of the experiment, there were significant decreases in mean arterial pressure
      (from 104 +/- 15 to 57 +/- 20 mm Hg), pH (from 7.46 +/- 0.04 to 7.24 +/- 15),
      Pao2 (from 528 +/- 35 to 129 +/- 104 torr [70.4 +/- 4.7 to 17.2 +/- 13.9 kPa]),
      and temperature (from 38.2 +/- 1 to 36.2 +/- 1.2 degrees C) in the high tidal
      volume group, whereas no significant differences were found in the low tidal
      volume group. Decreased alveolar permeability was shown in the low tidal volume
      group, as was decreased extravascular lung water in the uninstilled lung in the
      low tidal volume group (12.7 +/- 2.5 vs. 4.3 +/- 0.45 g H2O/g dry lung). No
      noteworthy difference was noted in the time course of bacteremia, although there
      was a trend toward earlier bacteremia in the high tidal volume group.
      CONCLUSIONS: In our animal model of P. aeruginosa-induced acute lung injury, low
      tidal volume ventilation was correlated with improved oxygenation, hemodynamic
      status, and acid-base status as well as decreased alveolar permeability and
      contralateral extravascular lung water.

PMID- 11246323
TI  - Interstitial brain adenosine and xanthine increase during jugular venous oxygen
      desaturations in humans after traumatic brain injury.
AB  - OBJECTIVE: Adenosine decreases the cerebral metabolic rate for oxygen and
      increases cerebral blood flow, and it may play an important role in
      cerebrometabolic and cerebrovascular responses to hypoperfusion after traumatic
      brain injury. Jugular venous oxygen saturation is monitored after traumatic brain
      injury to assess brain oxygen extraction, and desaturations may reflect secondary
      brain insults. We hypothesized that brain interstitial adenosine and related
      purine metabolites would be increased during jugular venous oxygen saturation
      desaturations (<50%) and determined associations between the purines, lactate,
      and glucose to assess the role of adenosine during secondary insults in humans.
      DESIGN: Study of critically ill adults with severe traumatic brain injury.
      SETTING: Adult neurointensive care unit. PATIENTS: We prospectively defined
      periods of normal saturation and desaturation in six patients after severe
      traumatic brain injury. INTERVENTIONS: During these periods, cerebral
      microdialysis samples of brain interstitial fluid were collected, and adenosine
      and purine metabolites were measured by high-pressure liquid chromatography.
      MEASUREMENTS AND MAIN RESULTS: Adenosine increased 3.1-fold and xanthine
      increased 2.5-fold during desaturation periods (both p <.05 vs. normal saturation
      period, signed rank). Adenosine, xanthine, hypoxanthine, and cyclic-adenosine
      monophosphate correlated with lactate over both study periods (r(2)
      =.32,.14,.31,.07, and.26, respectively, all p <.05, Pearson product moment
      correlation). CONCLUSION: The marked increases in interstitial brain adenosine
      that occur during jugular venous oxygen desaturations suggest that adenosine may
      play an important role during periods of secondary insults after traumatic brain
      injury. The correlation of these metabolites with lactate further suggests that
      adenosine is increased during periods of enhanced glycolytic metabolism.

PMID- 11246324
TI  - The role of gown and glove isolation and strict handwashing in the reduction of
      nosocomial infection in children with solid organ transplantation.
AB  - OBJECTIVE: Nosocomial infection is an important contributor to morbidity and
      mortality in pediatric solid organ transplantation. The relative effect of
      protective gown and glove isolation was compared with strict handwashing in
      pediatric intensive care unit (PICU) patients with solid organ transplantation.
      DESIGN/SETTING: A prospective, randomized design was used; children in a 23-bed
      PICU with solid organ transplantation were enrolled into a gown and glove
      protective isolation protocol or a strict handwashing protocol. PATIENTS: All
      children admitted to the PICU immediately after solid organ transplantation,
      excluding renal transplantation, and at subsequent readmissions to the PICU were
      eligible for the study. Children with current infection or known exposure to
      varicella were excluded from the study initially or at readmission.
      INTERVENTIONS: By using a block randomization design based on organ transplanted,
      age, and initial admission vs. readmission, each patient was randomized to either
      strict handwashing or protective gown and glove isolation intervention groups.
      MEASUREMENTS: We analyzed demographics, infection outcomes (defined according to
      Centers for Disease Control criteria), and monitoring of patient contacts in
      compliance with protocols. RESULTS: The infection rate in the overall PICU
      population did not change significantly from the year before the study compared
      with during the study (2.1 per 100 vs. 1.95 per 100 patient days; p =.4) The
      infection rate in the gown and glove group (2.3 per 100 patient days) was reduced
      significantly compared with the prestudy infection rate in the transplant
      population (4.9 per 100 patient days; p =.0008). Strict handwashing also
      significantly reduced the infection rate in the transplant population (3.0 per
      100 patient days; p =.008). Compliance with gowning and gloving was 82% and
      compliance with handwashing was 76% (compared with 22% before study [p <.0001]
      and 52% after the study [p <.0001]). Despite an increased mean length of stay in
      the PICU in the gown and glove group (p =.014), there was a trend toward
      reduction in the incidence of infection (Fisher's exact test, p =.07; odds
      ratio,.76) in the gown and glove group. CONCLUSIONS: Increased compliance with
      handwashing was associated with a reduction in nosocomial infections, and gown
      and glove isolation appeared to have an additional protective effect. Some
      nosocomial infections may be preventable in the pediatric solid organ
      transplantation population.

PMID- 11246325
TI  - Deadspace free ventilatory measurements in newborns during mechanical
      ventilation.
AB  - OBJECTIVE: To improve the accuracy of ventilatory measurements in ventilated
      newborns by means of a numerical correction when a deadspace free differential
      measuring method using two pneumotachographs (PNTs) is applied and to investigate
      the clinical usefulness of this correction procedure. DESIGN: In vitro study and
      prospective animal study. SETTING: Research laboratory of the Clinic of
      Neonatology and the Animal Research Laboratory, Charite Hospital Berlin.
      SUBJECTS: Ten newborn piglets, weighing 610-1340 g (median, 930 g), age <12 hrs.
      INTERVENTIONS: The accuracy of both the deadspace free method and the
      endotracheal flow measurements (conventional method) was investigated using
      mechanical lung models. A correction procedure for the deadspace free method was
      developed considering signal delay time and tube compliance between both PNTs.
      This method was applied to the piglets measured during partial liquid ventilation
      (PLV). Measurements were done before and after lung lavage and during 30 and 120
      mins of PLV (30 mL/kg body weight perfluorocarbon). MEASUREMENTS AND MAIN
      RESULTS: In vitro measurements showed volume differences between both methods of
      8%, 12%, 16%, and 17%, respectively, depending on the distance between the PNTs
      of 10, 60, 120, and 180 cm. After applying the correction algorithm, the
      differences decreased to 3%, 0%, -2%, and -8%, respectively. The piglets were
      measured with 120-cm tube length between the PNTs. The correction algorithm
      reduced the measured tidal volume before lavage by 7%, after lavage by 14%, 30
      min PLV by 12%, and 120-min PLV by 10%, corresponding to the changes in
      respiratory compliance of 1.2, 0.6, 1.0, and 1.1 mL/cm H2O. CONCLUSIONS: The
      deadspace free method can be advantageously used for continuous measurements in
      newborns despite much higher technical expense. The correcting procedure improved
      the accuracy of the volume measurement remarkably, especially for lower
      respiratory compliance.

PMID- 11246327
TI  - Critical care medicine for the 21st century.

PMID- 11246326
TI  - Accuracy and utility of a continuous intra-arterial blood gas monitoring system
      in pediatric patients.
AB  - OBJECTIVES: To determine the accuracy of the Paratrend 7 continuous intra
      arterial blood gas monitor (CI-ABGM) in radial and femoral artery catheters
      placed in children compared with simultaneous measurements of pH, Pa(CO2), and
      Pa(O2) performed by intermittent blood gas analysis. To determine sensor
      longevity in pediatric patients at different arterial sites. To determine the
      utility of CI-ABGM for tracking unanticipated events related to blood gas
      deterioration. SETTING: A pediatric intensive care unit of a university hospital.
      DESIGN: A prospective clinical investigation. PATIENTS: Fifty critically ill
      pediatric patients, ranging in age from 1 wk to 18 yrs of age, who required
      either radial or femoral artery catheters for intermittent arterial blood gas
      monitoring. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A Paratrend 7
      intra-arterial sensor was placed through either an 18- or 20-gauge catheter
      previously inserted into the radial or femoral artery. At clinically
      predetermined intervals ranging from every 1 to 8 hrs, the CI-ABGM measurements
      of pH, P(CO2), and P(O2) were compared with the values determined by standard
      intermittent blood gas analysis. The Paratrend 7 system values were individually
      adjusted to match ABG results when the Paratrend 7 pH differed by greater than +/
      0.05 units, P(CO2) was greater than +/-5 torr (0.7 kPa), and P(O2) was greater
      than +/-15% of the ABG value. Significant aberrations in gas exchange defined as
      unanticipated events were categorized as isolated metabolic acidosis (pH <7.20),
      hypercapnia (P(CO2), >70 torr; 9.3 kPa), and hypoxemia (P(O2), <50 torr; 6.7
      kPa). All unanticipated events were earmarked from consecutive monitoring epochs
      ranging from 4 to 24 hrs duration from the time of Paratrend 7 sensor insertion
      to the time of sensor removal. Fifteen sensors were placed into the radial
      artery, 34 sensors were placed into the femoral artery, and one sensor was
      initially placed in the radial and moved to a femoral artery location. Mean
      radial artery insertion duration was 35 hrs. Mean femoral artery duration was
      137.2 hrs. A total of 1445 pairs of ABG results were available for comparison.
      After removal of individual values, which did not meet inclusion criteria, 1411
      pH data pairs, 1408 P(CO2) data pairs, and 1326 P(O2) data pairs were analyzed.
      The bias and precision for the pH data were 0.00 and 0.04 units, respectively;
      for the P(CO2) data were -0.4 and 4.8 torr (-0.05 and 0.64 kPa), respectively;
      and for the P(O2) data 1.0 and 25 torr (0.1 and 3.3 kPa), respectively. Detection
      of unanticipated events was evenly spread across the three categories and was
      most commonly related to iatrogenic causes or cardiac failure. Persistent
      waveform dampening necessitating sensor removal was more frequently encountered
      in radial placement compared to femoral placement. CONCLUSIONS: The Paratrend 7
      CI-ABGM is accurate within the extremes of physiologic gas exchange typically
      encountered in the pediatric intensive care setting. The device is capable of
      tracking extreme fluctuations in gas exchange with a response rate suitable for
      making real-time therapeutic decisions. The sensor can be recommended for
      insertion into a femoral artery cannula. There is a high incidence of blood
      pressure waveform dampening encountered in radial artery use.

PMID- 11246328
TI  - Sclerosing cholangitis and liver cirrhosis after extrabiliary infections: report
      on three cases.
AB  - OBJECTIVE: To describe three unusual cases of sclerosing cholangitis after severe
      extrahepatic/extrabiliary bacterial infections. DESIGN: Case report, clinical.
      SETTING: Tertiary care intensive care unit (ICU). PATIENTS: Three patients
      admitted to the ICU with infections from Gram-positive bacteria followed by
      sclerosing cholangitis and secondary biliary cirrhosis. MAIN RESULTS: Three
      unusual cases of persisting cholestasis that occurred after bacterial infections
      originating from extrahepatic/extrabiliary foci are described. Endoscopic
      retrograde cholangiopancreatography and magnetic resonance
      cholangiopancreatography revealed multiple strictures of the intrahepatic bile
      ducts as a sign of sclerosing cholangitis. All patients progressed to biliary
      cirrhosis within months after the onset of cholestasis. CONCLUSION: Infection
      associated cholestasis is usually a functional disorder and subsides after
      effective treatment of the underlying inflammatory focus. In rare cases, however,
      extrahepatic/extrabiliary infections may lead to sclerosing cholangitis and
      secondary biliary cirrhosis via unknown mechanisms.

PMID- 11246329
TI  - Is blood transfusion good for the heart?

PMID- 11246330
TI  - Variability among institutional review boards and the value of local research
      context.

PMID- 11246331
TI  - Confusion reigns: enteral versus total parenteral nutrition.

PMID- 11246332
TI  - The hepatosplanchnic area and hyperlactatemia: A tale of two lactates.

PMID- 11246333
TI  - Caring for those who need critical care: understanding the patient experience.

PMID- 11246334
TI  - Adrenal tea leaves: Is the adrenal response to sepsis discernible?

PMID- 11246335
TI  - Tissue capnometry.

PMID- 11246336
TI  - Intramucosal pH titrated therapy: jumping to conclusions?

PMID- 11246337
TI  - Ventilation, cardiopulmonary bypass, and acute respiratory distress syndrome: Are
      the lungs the problem?

PMID- 11246338
TI  - Not all propofol is created equal.

PMID- 11246339
TI  - Acellular bronchial casts in children after cardiac surgery.

PMID- 11246340
TI  - Drug compatibility differences with propofol injectable emulsion products.

PMID- 11246341
TI  - Ernest Starling and the discovery of secretin.
AB  - The demonstration by Bayliss and Starling that acid liberates a chemical
      messenger from the cells of the duodenal and jejunal mucosa and that this, by
      traveling through the blood, excites the pancreas to secrete revolutionized
      physiology. It subsequently provided the impetus to establish endocrinology as a
      specialist field in medicine. Together, their contributions to physiology covered
      a vast sphere of knowledge, ranging from hormones to the heart and from enzymes
      to osmotic forces. Every subject that they studied was augmented by their
      efforts, and their lucid scientific writing brought both clarity and organization
      to the field of physiological endeavor throughout the world. Both contributed in
      a very definite way to crystallizing physiology into a rigorous scientific
      discipline and their respective texts the "Principles of General Physiology"
      (Bayliss) and the "Principles of Human Physiology" (Starling) established a
      framework of thought that for decades remained the lodestar of physiological
      science. As mentors, they devoted themselves to aspirant physiologists from all
      parts of the world, and their dedication to the activities of the Physiological
      Society in London was legendary. Indeed from 1896, when Starling became
      secretary, until the death of Bayliss in 1924, the two ran this august body in
      one capacity or another for more than a quarter of a century. There is little
      doubt that the felicitous collaboration that led to the discovery of secretin and
      the introduction of the concept of chemical messengers represents an advance that
      not only revolutionized physiological thought but the entire face of clinical
      medicine.

PMID- 11246342
TI  - Proximal small bowel enteropathy in patients with microscopic colitis: is it
      gluten-sensitive?

PMID- 11246343
TI  - Update on the pathologic approach to the diagnosis of gastritis, gastric atrophy,
      and Helicobacter pylori and its sequelae.
AB  - Biopsy sampling of the gastric mucosa at diagnostic endoscopy provides
      information that cannot be obtained otherwise. The most common indication for
      gastric biopsy is the need to know whether the patient is infected with
      Helicobacter pylori or not and whether the stomach is gastritic or not.
      Microscopic examination of gastric biopsy specimens gives, in addition to H.
      pylori status, information about the grade, extent, and topography of gastritis-
      and atrophy-related alterations in the gastric mucosa. This information provides
      further possibilities for the assessment of risk and likelihood of various
      gastric disorders. The presence of atrophy (loss of mucosal glands) results in
      failures in secretory functions of the corresponding mucosa and leads to errors
      in the homeostasis of normal gastric physiology. The grade of atrophy of the
      corpus mucosa linearly correlates with peak and maximal output of acid. The
      presence of advanced (moderate or severe) corpus atrophy indicates an extremely
      hypochlorhydric or achlorhydric stomach in which, for example, ordinary peptic
      ulcer is unlikely or impossible in spite of a possible H. pylori infection. Some
      well characterized and common topographic phenotypes of H. pylori gastritis and
      atrophic gastritis can be delineated as follows: Predominance or restriction of
      the H. pylori-related inflammation in antrum, in association with a nonatrophic
      corpus mucosa--of which phenotype is the most common--and with an increased risk
      of peptic ulcer disease, duodenal ulcer in particular ("duodenal ulcer phenotype"
      of gastritis); the presence of atrophic gastritis in corpus of the stomach
      ("corpus predominant gastritis"), which indicates a low risk of peptic ulcer and
      a reduction in the capacity of the patient to secrete acid; the occurrence of
      advanced atrophic gastritis and intestinal metaplasia multifocally in the stomach
      (advanced "multifocal atrophic gastritis"), which are features of a gastritis
      type and which also indicate a low acid secretion capacity and an increased risk
      of gastric neoplasias ("gastric cancer phenotype of gastritis"), suggesting a
      need for a careful exclusion of concomitant presence of small focal neoplastic or
      dysplastic lesions; and the presence of normal and healthy gastric mucosa, which
      indicates an extremely low risk of both peptic ulcer disease or gastric cancer
      and, therefore, is a finding of high clinical relevance. The presence of duodenal
      or gastric ulcer in conjunction with normal, healthy gastric mucosa suggests
      either aspirin or nonsteroidal antiinflammatory drugs to be the most likely cause
      of the ulcer.

PMID- 11246344
TI  - Nutrition in acute pancreatitis.
AB  - The majority of patients (80%) admitted with acute pancreatitis recovers after a
      few days of bowel rest and intravenous fluids. However, some cases progress to a
      fulminant disease complicated by a severe systemic inflammatory response and
      multiple organ failure, a condition in which mortality is related to the degree
      of negative nitrogen balance. The goal of nutrition support in this situation is
      to cover the increased metabolic demands without stimulating pancreatic secretion
      and exacerbating the "autodigestion" that characterizes the condition. Although
      human and animal studies have shown conflicting results regarding the effect of
      composition and location of feeding on pancreatic enzyme secretion, there is
      consensus that total parenteral nutrition (TPN), given at moderate infusion
      rates, does not significantly stimulate secretion in humans and that enteral
      diets stimulate enzyme secretion unless delivered below the jejunum.
      Consequently, until recently TPN has been the standard of therapy. The fact that
      the cost and complications of TPN can often outweigh its benefits (catheter
      sepsis, hyperglycemia) has led to a series of recent controlled clinical trials
      of modified enteral diets in which the diet is delivered by nasojejunal tube.
      Results have demonstrated that enteral nutrition, with either elemental or
      polymeric formulas, was cheaper, safer, and at the same time more effective in
      reducing the systemic inflammatory response. The pathophysiologic explanation for
      these observations needs further investigation.

PMID- 11246345
TI  - Helicobacter pylori and gastroesophageal reflux disease: lack of influence of
      infection on twenty-four-hour esophageal pH monitoring and endoscopic findings.
AB  - The precise role of Helicobacter pylori infection in gastroesophageal reflux
      disease (GERD) is a matter of intense debate. Twenty-four-hour esophageal pH
      monitoring has a higher accuracy than endoscopy for the diagnosis of GERD, but
      the correlation between H. pylori infection and esophageal pH-metric parameters
      has almost never been assessed. Therefore, we evaluated the relationship between
      the infection and the presence of disturbances not only in endoscopy but also in
      24-hour esophageal pH monitoring. One hundred consecutive patients undergoing 24
      hour esophageal pH monitoring because of symptoms suggestive of GERD were
      included in the study. Esophageal manometry was carried out to study the position
      and the pressure of the lower esophageal sphincter (LES). Prevalence of H. pylori
      infection was evaluated by histology (hematoxylin and eosin stain) and rapid
      urease test. The mean age of the patients was 50 +/- 15 years; 50% were men and
      56% had an abnormal pH-metry (DeMeester score more than 14.7). The prevalence of
      H. pylori in patients with abnormal pH-metry was 57% (95% CI, 42-70%) and was 52%
      (95% CI, 39-64%) in those with normal pH-metry (nonsignificant differences [NS]).
      In the multivariate analysis, H. pylori infection did not correlate with an
      abnormal pH-metry (odds ratio, 0.8; 95% CI, 0.4-1.8; NS). The proportion of cases
      with abnormal pH-metry among infected patients was 54% (95% CI, 41-66%) and was
      59% (95% CI, 44-72%) among uninfected patients (NS). Mean values of pH-metric
      parameters (+/-SD), respectively for H. pylori-positive and -negative patients,
      were total score (30 +/- 33 vs. 36 +/- 38), number of reflux episodes (7 +/- 7
      vs. 11 +/- 11), number of episodes more than 5 minutes (3.7 +/- 5 vs. 3.8 +/- 5),
      longest reflux episode (2.4 +/- 2 minutes vs. 3.1 +/- 3 minutes), and fraction
      time (%) with pH less than 4 (total, 6 +/- 7 vs. 6.8 +/- 8; upright, 3.9 +/- 4
      vs. 4.5 +/- 5; supine, 7.4 +/- 12 vs. 7.2 +/- 10) (all findings were NS).
      Endoscopic findings, respectively for H. pylori-positive and -negative, were
      hiatus hernia (41% vs. 41%), endoscopic esophagitis (Savary-Miller) (54% vs.
      46%), and Barrett's esophagus (15% vs. 11%) (all findings were NS). Finally,
      differences were not demonstrated in the pressure of the lower esophageal
      sphincter (12 +/- 8 mmHg vs. 14 +/- 12 mmHg) among H. pylori-positive and 
      negative patients. H. pylori infection is not associated with gastroesophageal
      reflux disease, as evaluated endoscopically and with 24-hour esophageal pH
      monitoring.

PMID- 11246346
TI  - Helicobacter pylori prevalence in patients with diabetes and its relationship to
      dyspeptic symptoms.
AB  - As available data on Helicobacter pylori infection in patients with diabetes are
      scattered and discordant, we evaluated the prevalence of H. pylori and its
      relationship to dyspeptic symptoms in adult patients with diabetes and subjects
      with dyspepsia. H. pylori infection (evaluated using the 13C urea breath test)
      and dyspeptic symptoms (nausea, bloating, and epigastric distress) were
      investigated in 71 consecutive diabetic outpatients; the presence of gross
      lesions, histologic gastritis, and Helicobacter was verified in the patients with
      a positive urea test who agreed to undergo upper gastrointestinal tract
      endoscopy. Seventy-one age- and gender-matched subjects with dyspepsia were used
      as controls. Helicobacter pylori infection was detected in 49 (69%) patients with
      diabetes and in 33 (46%) subject with dyspepsia (p = 0.007). Helicobacter pylori
      was present in 27 (77%) of 35 patients with diabetes with dyspeptic symptoms and
      in 22 (61%) of 36 patients without dyspeptic symptoms. Endoscopy revealed peptic
      ulcers in 13 of 23 patients; H. pylori infection was histologically confirmed in
      the gastric antrum of all patients with diabetes, and in the body of the stomach
      in 74%. The significantly higher prevalence of H. pylori infection in the
      patients with diabetes may partially explain their dyspeptic symptoms. The high
      prevalence of H. pylori infection, esophagitis, and peptic ulcers found in our
      patients with diabetes (with or without dyspepsia) suggests that this population
      should be considered "at risk" for H. pylori infection and suitable candidates
      for treatment.

PMID- 11246347
TI  - Gastric corpus mucin expression after partial gastrectomy, in relation to
      colonization with Helicobacter pylori.
AB  - Twelve different genes for mucin have been described. MUC5AC and MUC6 encode the
      secreted apomucins of the stomach. A gradient from the surface epithelium
      (foveola) to the glands is typical for MUC5AC synthesis, whereas a gradient in
      the opposite direction was found for MUC6. Our goal was to determine the
      distribution of MUC5AC and MUC6 in the postoperative stomach, with relation to
      the H. pylori status. Gastric corpus biopsy specimens from patients who underwent
      partial gastrectomy were examined by immunohistochemistry for mucin gene (MUC5AC
      and MUC6) apoproteins. We used polyclonal antibodies for amino acid tandem
      repeats of both proteins. A scoring system (0-3) was used to assess staining
      intensity at four sites: the lumen, the foveola, the mucous neck cells, and the
      glands. Helicobacter pylori status was determined by histology and rapid urease
      test and was considered positive or negative when both tests were positive or
      negative, respectively. We studied 19 H. pylori-positive and 32 H. pylori
      negative patients. No significant change in MUC5AC or MUC6 synthesis and
      secretion was demonstrated between H. pylori-positive or -negative patients. A
      gradient similar to that shown for the intact stomach (from the surface
      epithelium to the glands) for MUC5AC protein and an increase of MUC6 protein
      presentation from the mucous neck cell to the glands were demonstrated. The
      pattern of MUC5AC protein synthesis was not different between H. pylori-positive
      and -negative patients in the postoperative stomach. MUC6 expression was higher
      in the foveola in H. pylori-positive patients, whereas there was no difference in
      the other cell layers.

PMID- 11246348
TI  - The effect of the eradication of Helicobacter pylori infection on hemorrhage
      because of duodenal ulcer.
AB  - The cost of a recurrently bleeding duodenal ulcer (DU) is very high, both from a
      human and an economic point-of-view. Helicobacter pylori infection plays an
      important role in the pathogenesis of DU disease and its complications, such as
      bleeding. Cure of H. pylori infection is recommended in patients with DU and its
      complications, although in the latter case, the most efficient management is not
      yet a defined issue. In particular, acid secretion inhibitors may not contribute
      to long-term cure. Our aims were to ascertain whether the recurrence of bleeding
      because of DU could be prevented by H. pylori eradication and whether long-term
      inhibition of gastric acid output is needed to prevent recurrence. Eighty-four
      patients (65 men; mean age, 55.1 years), who had bled because of recurrent DU,
      were followed after the cure of H. pylori infection. None of the patients were on
      therapy with nonsteroidal antiinflammatory drugs. Successful cure of H. pylori
      was determined by gastroscopy, histology, and serology performed at 3, 6, 12, 24,
      and 48 months after the eradication treatment. A 13C urea breath test was
      performed when the results of serology were unclear and also at recurrence of DU
      or bleeding. After the antibiotic treatment, 46 patients stopped all medications,
      whereas 38 continued long-term therapy with histamine type 2 receptor
      antagonists. During a mean follow-up period of 47.2 months (range, 37-65 months),
      recurrence of DU at endoscopy was observed in three patients in each group (p =
      0.56), but none bled again. We conclude that H. pylori eradication prevents DU
      recurrence and rebleeding, that reinfection rate by H. pylori after cure was nil
      at 4 years, and that long-term inhibition of acid secretion may not improve
      outcome after cure of H. pylori, even in patients whose DU was complicated by
      hemorrhage.

PMID- 11246349
TI  - Celiac disease is highly prevalent in lymphocytic colitis.
AB  - A high frequency of celiac disease is reported in patients with collagenous
      colitis. Limited information is available on the frequency of celiac disease in
      lymphocytic colitis. The aim of our study was to determine the prevalence of
      celiac disease in microscopic colitis (collagenous and lymphocytic colitis).
      Patients were identified from a pathology registry of microscopic colitis from
      1987 to 1999. Pathology reports and medical records were reviewed for previous
      small bowel biopsies and/or celiac serology. We identified 113 patients with
      microscopic colitis, and 46 patients underwent a small bowel biopsy and/or celiac
      serology. Of these, 27 patients had lymphocytic colitis (63% female; age, 58.6 +/
      16.2 years) and 19 patients had collagenous colitis (79% female; age, 61.8 +/-
      13.6 years). Small bowel biopsy alone was performed in 28 of 46 patients, celiac
      serology alone was performed in 10, and both small bowel biopsy and celiac
      serology were performed in 8. Celiac disease was identified in 4 patients by
      small bowel histology; all had lymphocytic colitis (4 of 27 patients, 15%). This
      frequency of celiac disease is significantly higher than the highest reported
      U.S. prevalence of celiac disease (4/1,000 individuals; p < 0.01). There is a
      high frequency of celiac disease in patients with lymphocytic colitis. Given the
      importance of the early detection of celiac disease, it should be excluded in all
      patients with lymphocytic colitis, particularly if diarrhea does not respond to
      conventional treatment.

PMID- 11246350
TI  - Effect of chemotherapy with 5-fluorouracil on intestinal permeability and
      absorption in patients with advanced colorectal cancer.
AB  - 5-Fluorouracil (5-FU), in association with leucovorin (LV), is the most used
      chemotherapy agent in the treatment of colorectal cancer. Response rate, as well
      as side-effect incidence, increases with the dose intensity of regimens that are
      used. The most common dose-limiting toxicity for 5-FU/LV modulation is diarrhea.
      To assess the modification of small intestinal function, we investigated the
      changes in intestinal permeability (IP) and intestinal absorption (IA) in 41
      chemo-naive patients (21 men and 22 women; mean age, 61 +/- 9 years) with
      advanced colorectal cancer after treatment with the association of folinic acid
      and 5-FU. After chemotherapy administration, we found a marked increase in IP and
      a reduction in IA, measured as cellobiose-mannitol (CE-MA) ratio (p < 0.0001) and
      D-xylose absorption (p = 0.0001), respectively. Patients who experienced diarrhea
      have an increase in CE-MA ratio and a reduction in D-xylose absorption values,
      both statistically significant. Cellobiose-mannitol ratio and D-xylose absorption
      tests can be used for the assessment of toxic effect of 5-FU on mature intestinal
      epithelium and also for evaluating the role of cytoprotective agents.

PMID- 11246352
TI  - Utility of retroflexion in lower gastrointestinal endoscopy.
AB  - Although recommended, retroflexion to evaluate the rectal vault is not always
      practiced in endoscopy. A prospective study of 600 consecutive patients
      undergoing flexible sigmoidoscopy or colonoscopy was done to evaluate whether
      retroflexion increased the diagnostic yield compared with straight view
      examination of the distal rectum and whether the findings altered subsequent
      patient management. In this study, 30 patients were found to have distinct
      lesions in the anorectum. More than 50% of lesions in the rectal vault were
      identified only by retroflexion. Adenomatous polyps were seen in nine patients,
      of which six were identified only by retroflex view. Fifty percent of patients
      with adenomatous polyps in the rectal vault identified only by retroflexion
      during screening sigmoidoscopy were found to have right sided adenomas on
      colonoscopy. The retroflex view produced significant additional information,
      compared with standard forward view of the rectum, and altered the patient
      management plan. The procedure was easily performed without complications and was
      tolerated well by patients. Unless contraindicated, rectal retroflexion should be
      universally practiced and emphasized in training as more nonphysicians become
      involved in performing sigmoidoscopy.

PMID- 11246351
TI  - The analysis of resectability and survival in pancreatic cancer patients with
      vascular invasion.
AB  - One of the major limitations of curative resection in patients with pancreatic
      cancer is local tumor extension to the mesenteric vessels. Thus, the purposes of
      our study were to assess the clinical value of contrast-enhanced spiral computed
      tomography (CT) in predicting the resectability and survival of patients with
      pancreatic cancer with suspicious vascular invasion and to assess the influence
      of curative resection on the survival of these patients. We enrolled 40 patients
      with pancreatic cancer who were suspected of having an involvement of the
      adjacent large vessels and who subsequently underwent operation with curative
      intent in the study. Resectability and survival were correlated with CT findings
      such as segment length, degree of encasement, and type and number of vessels
      involved. The survival rate was compared between the curative and palliative
      resection groups, and survival rate was compared between the resected and
      unresected groups. Of the 40 patients with adenocarcinoma of the pancreas, 14 had
      curative resections and 26 had palliative resections. The probability of curative
      resection was higher in patients with segment lengths less than 2 cm, as compared
      with segment lengths more than 2 cm. However, there was no difference in survival
      between the two groups. There were no differences in resectability and survival
      according to the degree of encasement and type and number of vessels involved.
      There was no difference in survival between the curative and palliative resection
      groups. There was no difference in survival between the resected and unresected
      groups. A survival benefit was not achieved by curative resection in patients
      with pancreatic cancer with vascular invasion. Therefore, it would be better to
      avoid aggressive surgery in patients with pancreatic cancer with vascular
      invasion.

PMID- 11246353
TI  - The effect of stimulant laxatives and polyethylene glycol-electrolyte lavage
      solution for colonoscopy preparation on serum electrolytes and hemodynamics.
AB  - We have previously shown that magnesium citrate or bisacodyl before polyethylene
      glycol electrolyte lavage solution (PEG-ELS) improves colonoscopy preparation.
      Patients prefer this to preparation with full-volume PEG-ELS alone. However, such
      combinations might cause undesirable changes in hemodynamics or serum
      electrolytes. This study examined the effects of these combinations on heart
      rate, blood pressure, and serum electrolytes. We randomized 68 consecutive
      patients undergoing colonoscopy to one of three preparations. Group 1 received 4
      L of PEG-ELS, group 2 received 2 L of PEG-ELS with 20 mg bisacodyl, and group 3
      received 2 L of PEG-ELS preceded by 296 mL of magnesium citrate. Heart rate,
      blood pressure, and serum electrolytes were measured before starting the
      preparation and immediately before colonoscopy. Mean serum magnesium fell by 0.01
      mg/dL and 0.11 mg/dL in groups 1 and 2, respectively, and rose by 0.06 mg/dL in
      group 3 (p = 0.044). There were no other significant changes. Statistically
      significant changes in serum magnesium after preparation with PEG-ELS and a
      stimulant laxative are minor and probably of no clinical relevance. Two liters of
      PEG-ELS with a stimulant laxative is safe and effective for colonoscopy.

PMID- 11246354
TI  - Clinical, virologic, and pathologic significance of elevated serum alpha
      fetoprotein levels in patients with chronic hepatitis C.
AB  - Elevated serum alpha-fetoprotein (AFP) in patients with chronic hepatitis C is
      not uncommonly seen, but the pathogenesis of this phenomenon remains unclear. The
      aims of this study were to assess the prevalence of elevated serum AFP in
      patients with chronic hepatitis C and to evaluate the clinical, virologic, and
      histopathologic significance of this phenomenon. One hundred and fifteen Chinese
      patients with a histologic diagnosis of chronic hepatitis C were enrolled. None
      had evidence of hepatocellular carcinoma by image study at enrollment and for at
      least 2 years' follow-up. Of the 115 patients, 33 (29%) had elevated serum AFP
      (more than 12 ng/mL). There was a significantly lower mean serum albumin (4.0 +/-
      0.1 vs. 4.3 +/- 0.1 gm/dL, p <0.001) and higher mean scores for periportal
      necroinflammation (3.3 +/- 0.3 vs. 2.3 +/- 0.2, p = 0.007) and fibrosis (2.3 +/-
      0.2 vs. 1.1 +/- 0.1, p < 0.001) in patients with elevated serum AFP when compared
      with patients without elevated serum AFP. Patients with elevated serum AFP had
      significantly more incidences of genotype 1b infection when compared with
      patients without elevated serum AFP (77% vs. 51%, p = 0.021). Mean serum
      hepatitis C virus (HCV) RNA titer showed no significant difference between the
      two groups. Multivariate logistic regression analysis showed that as serum
      albumin of less than 4.2 gm/dL, a histology fibrotic score of more than 3, and
      HCV genotype 1b infection were significantly independent predictors associated
      with elevated serum AFP. In conclusion, elevated serum AFP levels were
      significantly correlated with lower serum albumin levels, advanced
      fibrosis/cirrhosis, and genotype 1b infection in patients with chronic hepatitis
      C.

PMID- 11246355
TI  - Autoimmune hemolytic anemia in treatment-naive chronic hepatitis C infection.
AB  - Extrahepatic immunologic abnormalities have been shown to occur in patients with
      chronic hepatitis C virus (HCV) infection. Induction of autoimmune hemolytic
      anemia has been reported, either during or after interferon treatment of HCV
      infection. I report a 48-year-old patient with HCV infection who developed Coombs
      positive autoimmune hemolytic anemia in the absence of treatment with interferon,
      with a review of the available literature. Other potential etiologies of
      autoimmune hemolytic anemia were ruled out. Prednisone therapy was instituted
      because of the severity of the fall in the hemoglobin. There was resolution of
      the hemolytic anemia and the prednisone was tapered gradually. No deterioration
      of the underlying HCV liver disease was evident even though an increase in HCV
      viremia was noted. Coombs-positive autoimmune hemolytic anemia can occur as an
      extrahepatic immunologic abnormality in treatment-naive patients with chronic HCV
      infection.

PMID- 11246356
TI  - Ulcerative colitis and thrombotic thrombocytopenic purpura.
AB  - Inflammatory bowel disease is often associated with hematologic abnormalities
      such as anemia, leukocytosis, and thrombocytosis. We report for the first time an
      unusual case of ulcerative colitis complicated by thrombotic thrombocytopenic
      purpura. Severe lower gastrointestinal bleeding resolved with subtotal colectomy,
      but the thrombotic thrombocytopenic purpura proved unresponsive to medical
      treatment. Splenectomy and completion proctectomy were performed, ultimately
      resulting in a successful outcome.

PMID- 11246357
TI  - Pleuropericarditis and disseminated intravascular coagulation in ulcerative
      colitis.
AB  - We report a 30-year-old woman with pleuropericarditis, cardiac tamponade, and
      disseminated intravascular coagulation complicating active ulcerative colitis
      (UC). Other autoimmune diseases were not present. She responded to pulsed steroid
      therapy and anticoagulant with resolution of the complication and UC. We reviewed
      the literature and found 27 cases of pleuropericarditis associated with
      idiopathic inflammatory bowel disease (IBD). It has been reported that
      pleuropericarditis associated with IBD responds well to nonsteroidal
      antiinflammatory drugs, as well as steroids. The causes of cardiac involvement in
      IBD remain unclear, but the pleuropericarditis must be recognized as a potential
      extraintestinal manifestation of IBD.

PMID- 11246358
TI  - Jaundice caused by a pancreatic mass: an exceptional presentation of Crohn's
      disease.
AB  - It is well known that Crohn's disease can involve the pancreas. However,
      granulomatous inflammation of the pancreas causing jaundice is extremely rare. In
      this report, we describe a patient presenting with jaundice in whom a Whipple
      procedure was performed because of the suspicion of a malignant pancreatic tumor.
      However, on histologic examination a benign granulomatous pancreatic mass was
      found. Further investigations revealed no other organ involvement and no
      underlying disease could be identified. Therefore, the tentative diagnosis of an
      idiopathic inflammatory pseudotumor was made. Only 6 months later, when the
      patient developed bloody diarrhea, Crohn's disease was diagnosed. This case
      stresses that, especially in young patients, Crohn's disease should be included
      in the differential diagnosis of benign common bile duct strictures even if no
      other symptoms of Crohn's disease are present.

PMID- 11246359
TI  - Panniculitis and arthritis as the presenting manifestation of chronic
      pancreatitis.
AB  - Although rare, panniculitis and polyarthritis can be the presenting
      manifestations of pancreatitis. Early recognition of this triad is critical
      because of the high mortality rate from pancreatic disease when the diagnosis is
      delayed. We report a patient with chronic alcohol intake whose sole presentation
      was severe polyarthritis and skin lesions secondary to chronic pancreatitis
      associated with extra pancreatic pseudocyst. Both arthritis and skin lesions
      disappeared after partial pancreatectomy and pancreatic stent insertion for a
      pancreatic duct stricture.

PMID- 11246360
TI  - Idiopathic pylephlebitis and idiopathic sclerosing peritonitis in a man with
      protein S deficiency.
AB  - Idiopathic pylephlebitis and primary sclerosing peritonitis are two highly
      unusual entities. To our knowledge, the association of the two diseases has not
      been described previously. We report a 42-year-old patient with a protein S
      deficiency who presented with fever and chills, in whom idiopathic pylephlebitis
      was diagnosed. A year later, the patient was readmitted because of recurrent
      vomiting and weight loss. An exploratory laparotomy yielded diagnosis of
      sclerosing peritonitis, which resolved after surgery. The short time interval
      between the processes suggests that they were related to each other, and also to
      the protein S deficiency.

PMID- 11246361
TI  - Leishmaniasis diagnosed by liver biopsy: management of two atypical cases.
AB  - Two patients presenting with pyrexia of unknown origin were diagnosed as having
      visceral leishmaniasis based on the presence of Leishmania donovani bodies in
      liver tissue. Of particular interest is that these two case reports suggest that
      in patients with pyrexia of unknown origin, a liver biopsy for L. donovani bodies
      should be considered even when several months have passed since leaving an
      endemic area, when splenomegaly is absent, when bone marrow examination and
      serology are not diagnostic, and even when abnormal coagulation necessitates a
      transjugular liver biopsy.

PMID- 11246362
TI  - The "serendipitous" surgical cure of the Zollinger-Ellison syndrome in a patient
      with multiple endocrine neoplasia type 1 despite an unsuspected diagnosis of
      either disease.
AB  - Zollinger-Ellison syndrome (ZES) is a relatively uncommon disease that usually
      presents with peptic ulcer disease or refractory diarrhea. It occurs as a
      component of multiple endocrine neoplasia type 1 (MEN-1) syndrome in more than
      25% of cases. Surgical management of MEN-1 ZES remains controversial. In this
      case report, we describe the serendipitous cure of ZES in a patient with
      recurrent peptic ulcer disease who underwent two surgical procedures. The
      diagnosis of MEN-1 ZES syndrome was neither suspected nor recognized during
      either operation. This case is presented to highlight the important principles in
      the diagnosis and current management of patients with MEN-1 ZES.

PMID- 11246363
TI  - Helicobacter pylori-related gastric outlet obstruction: is there a role for
      medical treatment?
AB  - The role of Helicobacter pylori in the pathogenesis of duodenal and gastric ulcer
      and ulcer recurrence is widely known. Bleeding, perforation, and gastric outlet
      obstruction represent the most serious, potentially life-threatening
      complications of ulcer disease. At present, the effect of H. pylori eradication
      on complicated ulcer disease has not been fully established. Case reports exist
      on the resolution of gastric outlet obstruction after eradication of H. pylori.
      We report the first case of H. pylori-related gastric outlet obstruction
      successfully treated with parenteral antibiotics.

PMID- 11246364
TI  - Delayed orocecal transit time and bacterial overgrowth in Crohn's disease.

PMID- 11246365
TI  - The etiology of hepatic granulomas.

PMID- 11246366
TI  - Acute pancreatitis possibly related to finasteride.

PMID- 11246367
TI  - Immune thrombocytopenic purpura, profuse diarrhea, and new onset ulcerative
      colitis: a dramatic response to splenectomy.

PMID- 11246368
TI  - The reliability of urease tests for Helicobacter pylori in childhood.

PMID- 11246369
TI  - Lumbar disc herniation: a new equilibrium is needed between nonoperative and
      operative treatment.

PMID- 11246370
TI  - Effects of electrical stimulation of the sciatic nerve on background
      electromyography and static stretch reflex activity of the trunk muscles in rats:
      possible implications of neuronal mechanisms in the development of sciatic
      scoliosis.
AB  - STUDY DESIGN: The effects of electrical stimulation of the sciatic nerve on
      background electromyographic and static stretch reflex activity of the trunk
      muscles were studied. OBJECTIVES: To verify the hypotheses that sciatic scoliosis
      is induced reflexively by radiculopathic pain, and that scoliosis might be
      maintained by prolonged asymmetric alteration of the trunk muscle tonus caused by
      central sensitization of the spinal neurons that constitute the postural reflex
      pathways. SUMMARY OF BACKGROUND DATA: Sciatic scoliosis usually occurs with
      convexity to the side of the herniated disc. The neuronal mechanism of sciatic
      scoliosis has not been well clarified. Recently, prolonged alteration of motor
      function in the hindlimbs of animals caused by central sensitization has been
      reported. METHODS: In spinalized rats (transection of the spinal cord), the
      sciatic nerve was stimulated electrically as a conditioning stimulus. Muscle
      stretch elicited by bending of the lumbar spine was applied as a test stimulus.
      Background and stretch reflex activities of the bilateral oblique abdominal,
      psoas, and quadratus lumborum muscles were recorded. Rats in which MK-801, an N
      methyl-d-aspartate antagonist, was preadministered also were used. RESULTS: The
      conditioning stimulus enhanced background electromyographic activity in bilateral
      oblique abdominal, contralateral psoas, and quadratus lumborum muscles.
      Furthermore, the conditioning stimulus induced prolonged facilitation and
      depression of stretch reflex activity of the contralateral psoas and quadratus
      lumborum, and ipsilateral psoas and quadratus lumborum muscles, respectively.
      Preadministration of MK-801 reduced these excitatory and inhibitory effects.
      CONCLUSION: It was found that the pattern of electromyographic activity of the
      trunk muscles evoked by sciatic nerve stimulation coincided with the typical
      direction of sciatic scoliosis in patients with lumbar disc herniation. It was
      supposed that the prolonged asymmetric alteration of the trunk muscle tonus was
      caused by central sensitization, and that central sensitization of spinal neurons
      may underlie the neuronal mechanism of sciatic scoliosis.

PMID- 11246371
TI  - Intervertebral disc composition in neuromuscular scoliosis: changes in cell
      density and glycosaminoglycan concentration at the curve apex.
AB  - STUDY DESIGN: An analysis of the variation in glycosaminoglycan, water content,
      and cell density with disc level in patients with neuromuscular scoliosis.
      OBJECTIVES: To determine whether the composition of the apical disc differed from
      that of adjacent discs in the same spine. SUMMARY OF BACKGROUND DATA:
      Compositional differences between the convex and concave sides of scoliotic discs
      have been noted and are thought to be secondary to altered loading. However,
      there is little information on changes relative to the apex. METHODS: Intact
      wedges of disc obtained during anterior fusion procedures were taken from 23
      discs of 6 patients with neuromuscular scoliosis. Radial profiles of
      glycosaminoglycan, water content, and cell density were measured. Concentrations
      were compared at a standard distance (5 mm) into the disc and plotted versus
      spinal level. RESULTS: Glycosaminoglycan and water content were lowest in the
      outer annulus and increased steadily toward the disc center, whereas the cell
      density was highest in the outer 2 mm, fell steeply and then remained constant.
      At 5 mm from the annulus edge, cell density was lowest in apical discs and, in
      most cases, was noticeably higher in adjacent discs of the same spine. At the
      same point, there was no consistent change in glycosaminoglycan/dry weight from
      disc to disc, indicating no significant proteoglycan loss. However,
      glycosaminoglycan/tissue water, and therefore swelling pressure, was highest in
      the apical discs, suggesting that these discs were the most heavily loaded.
      CONCLUSIONS: The loss of cells from the disc at the curve apex probably arose
      because this disc experiences greater mechanical stress or is more deformed than
      its neighbors. The decrease in cell density was not associated with major changes
      in tissue composition, possibly because rates of degradation and of synthesis
      were reduced, leaving the matrix largely unchanged.

PMID- 11246372
TI  - Expression of Fas ligand and apoptosis of disc cells in herniated lumbar disc
      tissue.
AB  - STUDY DESIGN: An examination of surgically obtained herniated lumbar disc tissues
      performed by using immunohistochemical staining and the DNA nick end labeling
      method. OBJECTIVE: To investigate the cell type that expresses Fas ligand (FasL)
      and any evidence of apoptosis of the disc cells in herniated lumbar disc tissues.
      SUMMARY OF BACKGROUND DATA: The Fas/FasL system is involved in delivering a death
      signal that rapidly commits the cells to apoptosis. In the authors' previous
      study, the expression of Fas on disc cells was identified in herniated lumbar
      disc tissue. METHODS: Twenty-three herniated lumbar disc tissues (contained disc,
      n = 9; noncontained disc, n = 14) were examined to investigate the cell type that
      expresses FasL and any evidence of apoptosis of the disc cells by using
      immunohistochemical staining and the DNA nick end labeling method, respectively.
      The percentage of FasL-positive disc cells was calculated and compared with
      clinical and radiologic data. RESULTS: FasL was expressed in the cytoplasm of the
      disc cells, and nuclear DNA fragmentation in a few disc cells was identified. A
      higher degree of FasL expression in disc cells was found in noncontained discs
      than in contained discs (P < 0.05). The percentage of FasL-positive disc cells
      significantly increased with the patient's age (P < 0.05), but not with the
      degree of disc degeneration (P > 0.05). CONCLUSION: The current results indicate
      that disc cells, after herniation, undergo apoptotic cell death via autocrine or
      paracrine FasL mechanisms by the disc cells themselves.

PMID- 11246373
TI  - Histochemical changes in the multifidus muscle in patients with lumbar
      intervertebral disc herniation.
AB  - STUDY DESIGN: The histochemical changes in the multifidus muscle in 29 patients
      with L4-L5 lumbar intervertebral disc herniation were studied. OBJECTIVES: To
      clarify how nerve root impairment affects the histochemical properties of the
      lumbar multifidus muscle in patients with lumbar intervertebral disk herniation.
      SUMMARY OF BACKGROUND DATA: There have been several studies on histochemical
      changes in lumbar muscles in patients with nerve root impairment, but the
      findings concerning changes in muscle fiber sizes vary among investigators.
      METHODS: Biopsy specimens were obtained intraoperatively from the L4 and L5 bands
      of the multifidus muscle on the affected and nonaffected sides. The specimens
      were stained with ATPase to evaluate the size of the fibers and structural
      changes. RESULTS: In the L5 muscle band, the mean sizes of Type 1 and Type 2
      fibers on the affected side were significantly smaller than those on the
      nonaffected side (Type 1: P < 0.01, Type 2: P < 0.001). The decrease in size was
      6.4% for Type 1 and 9.8% for Type 2. Increased percentages of Type 1 fibers and a
      high incidence of small angular fibers and fiber type grouping were also shown on
      the affected side. In contrast, in the L4 muscle band, no side-to-side
      differences in the histologic findings were observed. There was no significant
      level-to-level difference in the mean size of Type 1 or Type 2 fibers on either
      the affected or the nonaffected side. CONCLUSIONS: These results suggest that
      nerve root impairment leads to atrophy of Type 1 and Type 2 fibers, with
      structural changes in the multifidus muscle only at the involved level.

PMID- 11246374
TI  - Is it possible to simulate physiologic loading conditions by applying pure
      moments? A comparison of in vivo and in vitro load components in an internal
      fixator.
AB  - STUDY DESIGN: Loads acting in an internal fixator measured in vitro under the
      application of pure moments such as those commonly used for implant testing and
      basic research were compared with loads measured in 10 patients in vivo.
      OBJECTIVES: To investigate whether these recommended loading conditions are valid
      by comparing in vivo measurements and those obtained in an in vitro experiment.
      SUMMARY OF BACKGROUND DATA: Pure bending moments are often preferred as loading
      conditions for spinal in vitro testing, either for implant testing or basic
      research. The advantage of this loading pattern is that the bending moment is
      uniform along the multisegmental specimen. However, functional loading of the
      spine by muscles or external loads subjects the spine to a combination of forces
      and moments. METHODS: In an in vivo experiment, loads acting on an internal
      spinal fixator in 10 patients were determined before and after anterior interbody
      fusion during flexion, extension, left and right lateral bending, and left and
      right axial twisting of the upper body with the patient standing. For comparison,
      an equivalent in vitro data set was created with 7 human lumbar specimens in
      which the same type of fixator was used. All specimens were tested under the
      application of pure bending moments in the three main motion planes in the intact
      state with fixator, after corpectomy, and with bone graft. RESULTS: Consistent
      qualitative agreement between in vivo and in vitro measurements for the loads
      acting in the internal spinal fixator were found for axial rotation and lateral
      bending. For flexion and extension, reasonable agreement was found only for the
      intact spines with fixators. After corpectomy and after inserting a bone graft,
      the median values for axial force and bending moment in the sagittal plane in
      vitro did not agree with in vivo measurements. An axial preload in the in vitro
      experiment slightly increased the axial compression force and flexion bending
      moment in the fixators. CONCLUSIONS: The application of pure moments to intact
      lumbar spinal specimens in vitro produces forces and moments in implants
      comparable with loads observed in vivo. During basic research on intact specimens
      or implant testing involving a removed disc or corpectomy, muscle forces are
      necessary to simulate realistic conditions.

PMID- 11246376
TI  - Increased fusion rates with cervical plating for three-level anterior cervical
      discectomy and fusion.
AB  - STUDY DESIGN: A retrospective review of all patients surgically treated by a
      single surgeon with a three-level anterior cervical discectomy and fusion with
      and without anterior plate fixation. OBJECTIVES: To compare the clinical and
      radiographic success of anterior three-level discectomy and fusion performed with
      and without anterior cervical plate fixation. SUMMARY OF BACKGROUND DATA:
      Previous studies of multilevel cervical discectomies and fusions have shown
      fusion rates to decrease as the number of surgical levels increases. Anterior
      cervical plate stabilization can provide more stability and may increase fusion
      rates for multilevel fusions. METHODS: Over a 7-year period, 59 patients were
      treated surgically with a three-level anterior cervical discectomy and fusion by
      the senior author. Forty patients had cervical plates, whereas 19 had fusions
      with no plates. These patients were observed for an average of 3.2 years.
      Clinical and radiographic follow-up data were obtained. RESULTS: Of the 59
      patients, 14 had a pseudarthrosis (7 in each group). The pseudarthrosis rates
      were 18% (7 of 40) for patients with plating and 37% (7 of 19) for patients with
      no plating. Although the nonunion rate for unplated fusions was double that of
      plated fusions, this difference was not statistically significant. There was no
      statistically significant correlation between pseudarthrosis and gender, age,
      level of surgery, history of tobacco use, or previous anterior surgery. The
      fusion rates were improved with the use of a cervical plate. Inferior clinical
      results were demonstrated in patients with a pseudarthrosis, regardless of the
      use of a cervical plate. CONCLUSIONS: The addition of plate fixation for three
      level anterior cervical discectomy and fusion is a safe procedure and does not
      result in higher complication rates. In this study, the pseudarthrosis rate was
      lower for patients with a cervical plate. However, this difference was not
      statistically significant. Patients treated with cervical plating had overall
      better results when compared with those of patients treated without cervical
      plates. Although the use of cervical plates decreased the pseudarthrosis rate, a
      three-level procedure is still associated with a high nonunion rate, and other
      strategies to increase fusion rates should be explored.

PMID- 11246377
TI  - Types of lumbar herniated disc and clinical course.
AB  - STUDY DESIGN: A retrospective study of different types of herniated discs and
      duration of symptoms in patients with lumbar disc herniation, and a trial of
      longer conservative treatment to reduce the number of operations. OBJECTIVE: To
      determine whether noncontained and contained herniated discs have different
      clinical courses and to evaluate the results of the clinical trial of longer and
      vigorous conservative treatment. SUMMARY OF BACKGROUND DATA: The possibility of a
      difference in clinical features between contained and noncontained disc
      herniation has been suggested previously. METHODS: In the first study, the
      medical history and intraoperative findings of 156 patients who had undergone
      herniotomy were reviewed. In the second study, conservative treatment of at least
      2 months' duration was recommended for all patients with lumbar disc herniation.
      RESULTS: In the first study, patients with noncontained disc herniation had a
      shorter preoperative clinical course than those with contained disc herniation.
      It was rare for noncontained herniation to require surgery 4 months or more after
      the onset of symptoms. In the second study, the authors' protocol reduced the
      number of herniotomies required, especially the number of operations for the
      patients with noncontained disc herniation. CONCLUSIONS: The authors believe that
      patients with noncontained lumbar disc herniation can be treated without surgery,
      if these patients can tolerate the symptoms for the first 2 months.

PMID- 11246379
TI  - Long-term outcomes of standard discectomy for lumbar disc herniation: a follow-up
      study of more than 10 years.
AB  - STUDY DESIGN: A retrospective analysis of the long-term outcomes of standard
      discectomy for lumbar disc herniation. OBJECTIVES: To investigate the long-term
      outcomes of standard discectomy to address postoperative problems, including
      residual low back pain and recurrent herniation. SUMMARY OF BACKGROUND DATA: Most
      previous investigators found that favorable outcomes of standard discectomy were
      maintained for the long-term postoperative period. Although they observed
      postoperative complications such as residual low back pain and recurrent
      herniation, detailed analyses of these results have not been conducted. METHODS:
      The long-term follow-up results in patients who were observed for a minimum of 10
      years after standard discectomy were evaluated by using the Japanese Orthopedic
      Association scoring system through direct examinations and questionnaires.
      Radiography also was used in patients who agreed to visit the hospital, and
      findings were compared with those on preoperative radiographs. RESULTS: The
      average recovery rate calculated by using Japanese Orthopedic Association scores
      was 73.5 +/- 21.7%. Even though residual low back pain was found in 74.6% of the
      patients, only 12.7% had severe low back pain. The majority of the patients with
      severe low back pain were under 35 years of age at the time of operation, with
      preoperative advanced disc degeneration. The final Japanese Orthopedic
      Association scores in the patients with decreased disc height were significantly
      lower than those in patients with no decrease. However, the disc height of
      patients with a recurrent herniation was preserved. CONCLUSION: The long-term
      outcome of standard discectomy in this series was favorable. Although patients
      with preserved disc height generally had favorable results, the risk of recurrent
      disc herniation was high in this population.

PMID- 11246381
TI  - Postoperative narcotic requirement after microscopic lumbar discectomy is not
      affected by intraoperative ketorolac or bupivacaine.
AB  - STUDY DESIGN: Prospective, randomized, double-blind study. OBJECTIVE: To assess
      the efficacy of ketorolac and bupivacaine in reducing postoperative pain after
      microsurgical lumbar discectomy. SUMMARY OF BACKGROUND DATA: Microsurgical lumbar
      discectomy often is performed as an ambulatory procedure. Pain, nausea, and
      urinary retention may delay discharge. It was hypothesized that intraoperative
      ketorolac or bupivacaine would reduce postoperative pain as measured by morphine
      demand. METHODS: After Institutional Review Board (IRB) approval and informed
      consent, 30 patients undergoing single-level microsurgical lumbar discectomy
      under general anesthesia randomly received either intravenous ketorolac,
      intramuscular bupivacaine, or placebo before wound closure. After surgery, all
      patients received intravenous, MSO4, patient-controlled analgesia. MSO4 demand
      was compared between groups at 30 minutes and at 1, 4, 8, 16, 20, and 24 hours
      after surgery by one-way ANOVA. Pre- and postoperative pain was assessed by using
      a standard scale and was correlated to postoperative MSO4 demand by Pearson
      correlation. Significance was assumed at P < 0.05. RESULTS: There were no group
      differences in age, gender, weight, disc level, preoperative pain, or
      preoperative use of pain medication. Neither ketorolac nor bupivacaine decreased
      pain or nausea scores, MSO4 demand, or time to void and ambulation. Preoperative
      pain was significantly correlated to postoperative narcotic demand (r = 0.46, P <
      0.01). Preoperative narcotic or NSAID use was not correlated to either
      preoperative pain scores or postoperative MSO4 requirement. CONCLUSIONS: Neither
      ketorolac nor bupivacaine decreased the postoperative narcotic requirement in
      patients undergoing microsurgical lumbar discectomy. Postoperative narcotic
      requirements are increased in patients who are in severe pain before surgery,
      regardless of preoperative narcotic use.

PMID- 11246382
TI  - Clinical features of extraforaminal lumbar disc herniation based on the
      radiographic location of the dorsal root ganglion.
AB  - STUDY DESIGN: The relations between the location of the dorsal root ganglion and
      pre- and postoperative symptoms were reviewed retrospectively in 27 patients who
      underwent radiculography and posterior discectomy. OBJECTIVES: To evaluate the
      clinical features and surgical outcome of extraforaminal lumbar disc herniation
      based on the location of dorsal root ganglion. SUMMARY OF BACKGROUND DATA: The
      location of dorsal root ganglia has been reported to be correlated with a variety
      of radicular symptoms. Extraforaminal lumbar disc herniation has several specific
      clinical features, one of which is severe radicular pain. However, there is no
      report in the literature on the association between the location of the dorsal
      root ganglia and the severity of the symptoms of extraforaminal lumbar disc
      herniation. METHODS: The radiographic location of the dorsal root ganglion of
      each compressed nerve root was determined by preoperative direct radiculograms.
      All patients were classified into the following three groups according to the
      location of dorsal root ganglion: intraspinal, intraforaminal, and
      extraforaminal. The incidences of these locations were 5 of 27 (18.5%), 15 of 27
      (55.5%), and 7 of 27 (25.9%), respectively. The relation between the location of
      the dorsal root ganglion and clinical parameters such as the level of the
      compressed nerve root, the degree of limitation on straight leg raising test, the
      severity of the pre- and postoperative subjective symptoms (leg pain, low back
      pain, and walking capacity), clinical signs (sensory and motor disturbance), and
      the recovery rate were investigated. RESULTS: The degree of limitation on the
      straight leg raising test in the extraforaminal group tended to be low, compared
      with that in the intraspinal and intraforaminal groups. Low back pain in the
      extraforaminal group was more severe than that in the intraspinal and
      intraforaminal groups. Preoperative leg pain in the extraforaminal group was
      significantly more severe that that in the intraspinal group, and the walking
      capacity in the extraforaminal group tended to be lower than that in the
      intraspinal and intraforaminal groups. No significant differences were found
      between the location of dorsal root ganglion and the preoperative sensory or
      motor disturbance and surgical outcomes. CONCLUSION: The location of the dorsal
      root ganglion might influence the severity of radicular symptoms (pain and
      walking distance tolerance) in patients with extraforaminal lumbar disc
      herniation.

PMID- 11246383
TI  - Lumbosacral scoliotic list by lumbar disc herniation.
AB  - STUDY DESIGN: A prospective study of 45 patients with lumbar disc herniation and
      scoliotic list who had undergone conventional open discectomy. OBJECTIVES: To
      determine the association between the location of the disc herniation and the
      direction of sciatic scoliotic list and to clarify the mechanism of sciatic
      scoliosis. SUMMARY OF BACKGROUND DATA: The association between the scoliotic list
      and lumbar disc herniation is well known. However, there have been few studies
      regarding the direction of scoliotic list and the location of the disc herniation
      observed during surgery. METHODS: The direction of scoliotic list, the
      preoperative and postoperative Cobb's angle, and the displacement of the first
      lumbar vertebra from the center sacral line were measured. The location, side,
      and degree of disc herniation were observed during surgery. RESULTS: There was no
      statistically significant association observed between the location or degree of
      nerve root compression and the direction or degree of sciatic scoliosis.
      Moreover, there was no statistically significant association observed between the
      location or degree of nerve root compression and the displacement of the first
      lumbar spine from the center sacral line. However, there was a significant
      association between the side of the disc herniation and the direction of sciatic
      scoliosis. Most of the sciatic scoliotic list disappeared after surgical
      decompression. CONCLUSION: The direction of sciatic scoliosis was not observed to
      be associated with the location of nerve root compression, although it was
      related to the side of disc herniation.

PMID- 11246384
TI  - Recurrent lumbar disc herniation: results of operative management.
AB  - STUDY DESIGN: A retrospective evaluation of 28 patients with recurrent lumbar
      disc herniation. OBJECTIVES: To analyze the outcome of the revisions (repeat
      discectomy), the risk factors of recurrent disc herniation, and the factors that
      influenced the outcomes of repeat discectomy. SUMMARY OF BACKGROUND DATA:
      Recurrent herniation following disc excision has been reported in 5-11% of
      patients. There have been many studies on recurrent disc herniation, but these
      studies have analyzed mixed patient populations. METHODS: Recurrent lumbar disc
      herniation was defined as disc herniation at the same level, regardless of
      ipsilateral or contralateral herniation, with a pain-free interval greater than 6
      months. Eight women and 20 men were studied. The levels of disc herniation were
      L4-L5 (19 cases) and L5-S1 (9 cases). Gadolinium-enhanced magnetic resonance
      imaging was performed in all patients. Revision surgery was performed in all
      patients by using conventional open discectomy. The pain-free interval, side and
      degree of herniation, operation time, duration of hospital stay, and clinical
      improvement rate were recorded. RESULTS: The mean pain-free interval was 60.8
      months. There were 21 cases of ipsilateral herniation and 7 cases of
      contralateral herniation. The degrees of herniation in revision were protrusion
      (14 cases), subligamentous extrusion (3 cases), transligamentous extrusion (8
      cases), and sequestration (3 cases). The degrees of herniation in the previous
      discectomy were protrusion (17 cases), subligamentous extrusion (10 cases), and
      transligamentous extrusion (1 case). The length of surgery was significantly
      different (P = 0.003) between the revision surgery and the previous discectomy.
      There were no significant differences between revision and previous surgery in
      terms of hospital stay or clinical improvement rates. Age, gender, smoking,
      professions, traumatic events, level and degree of herniation, and pain-free
      interval did not affect the clinical outcomes. CONCLUSION: Conventional open
      discectomy as a revision surgery for recurrent lumbar disc herniation showed
      satisfactory results that were comparable with those of primary discectomy. Based
      on the results of this study, repeat discectomy can be recommended for the
      management of recurrent lumbar disc herniation.

PMID- 11246386
TI  - Disc height and signal intensity of the nucleus pulposus on magnetic resonance
      imaging as indicators of lumbar disc degeneration.
AB  - STUDY DESIGN: A cross-sectional magnetic resonance imaging (MRI) study of
      degeneration of the lumbar spine. OBJECTIVES: To compare the usefulness of disc
      height and that of T2-weighted signal intensity as indicators of disc
      degeneration. SUMMARY OF BACKGROUND DATA: Disc height and signal intensity have
      been used as indicators for disc degeneration. Their relation to each other and
      to early degeneration has not been well documented. There is evidence that
      physical load can affect disc height. METHODS: Forty-one machine operators, 41
      construction carpenters, and 46 office workers, aged 40-45 years, and 22 students
      aged 18-20 years were examined with sagittal magnetic resonance imaging. All
      study participants were men. The mean value of the anterior and posterior disc
      height and the relative T2-weighted signal intensity of the nucleus pulposus of
      discs L2-L3 to L5-S1 were measured. RESULTS: Young men showed the lowest disc
      height but the highest relative signal intensity. Disc height showed an
      increasing trend from the office workers (sedentary) to blue-collar workers (more
      physical work) at all disc levels but L5-S1. Relative signal intensity showed a
      decreasing trend for these same worker types at all levels. In generalized linear
      modeling, signal intensity and the occupations, in reference to the young
      students, showed a significant effect on disc height. CONCLUSIONS: Relative
      signal intensity was lower in the middle-aged men than in the young men,
      indicating age-related disc degeneration. Despite the general positive
      association between disc narrowing and decreased relative signal intensity, disc
      narrowing may behave unexpectedly in relation to signal intensity and age. Signal
      intensity may be a more sensitive measure of disc degeneration. The validity of
      disc height as an indicator of early degeneration seems questionable.

PMID- 11246388
TI  - A modified technique for harvesting full-thickness iliac crest bone graft.
AB  - STUDY DESIGN: A prospective follow-up study of patients undergoing anterior
      spinal decompression and bone graft with cortical iliac crest bone. OBJECTIVE: To
      describe a modified technique for harvesting cortical bone graft from the
      anterior iliac crest. SUMMARY OF BACKGROUND DATA: Cortical bone graft from the
      iliac crest frequently is used in various orthopedic and spinal procedures. The
      resulting defect in the iliac crest has been associated with many complications.
      METHODS: Twenty patients were included in this study. All had burst vertebral
      fracture requiring anterior spinal decompression and cortical bone grafting. The
      modified technique was used for harvesting the iliac crest bone graft in all
      patients. RESULTS: All patients were satisfied with the appearance of the iliac
      crest. None reported chronic pain at the graft site. None had fracture of the
      iliac wing, and none had symptoms related to the lateral femoral cutaneous nerve
      or herniation of pelvic contents through the bony defect in the iliac wing.
      CONCLUSION: This modified technique is technically straightforward and cost
      effective. It preserves the contour and shape of the iliac crest and avoids
      cosmetic deformities and chronic pain at the graft site. It creates a window in
      the iliac wing rather than disrupting the continuity of the iliac crest, which
      leaves the iliac wing structurally stronger than with currently used techniques.

PMID- 11246385
TI  - Facet tropism: a comparison between far lateral and posterolateral lumbar disc
      herniations.
AB  - STUDY DESIGN: An assessment of the difference in the degree of facet tropism and
      disc degeneration between far lateral and posterolateral lumbar disc herniations.
      OBJECTIVE: To investigate the effect of the difference in the degree of the facet
      tropism and disc degeneration with respect to the development of far lateral
      lumbar disc herniation and posterolateral lumbar disc herniation, and to compare
      the effect between the two types of herniations. SUMMARY OF BACKGROUND DATA: The
      effect of facet tropism on the development of posterolateral lumbar disc
      herniation has been investigated previously, but there has been no study on far
      lateral lumbar disc herniation. METHODS: Thirty-eight lumbar disc herniations
      (far lateral, n = 19; posterolateral, n = 19) were included this study. The
      degree of facet tropism and disc degeneration was measured at the herniated disc
      level by using magnetic resonance imaging. The results were compared to show any
      differences between the two types of lumbar disc herniations. RESULTS: There were
      significant differences in the degree of facet tropism (24.74 vs. 14.26, P =
      0.004) and disc degeneration (23.92 vs. 15.08, P = 0.005) between the far lateral
      and posterolateral lumbar disc herniations. There was no significant correlation
      between the degree of facet tropism and the degree of disc degeneration in far
      lateral lumbar disc herniation (r = -0.369, P = 0.120). CONCLUSION: This results
      suggest that the differences in the degree of facet tropism and disc degeneration
      might be considered a key factor in distinguishing the development of far lateral
      lumbar disc herniation from that of posterolateral lumbar disc herniation.

PMID- 11246387
TI  - Nonautologous interbody fusion materials in cervical spine surgery: how strong is
      the evidence to justify their use?
AB  - STUDY DESIGN: A review of the literature concerning the use of interbody fusion
      devices and materials in anterior cervical surgery. OBJECTIVES: To examine the
      evidence supporting the use of interbody fusion devices as an alternative to
      autologous bone after anterior cervical discectomy. SUMMARY OF BACKGROUND DATA:
      Concerns over the morbidity associated with harvesting autologous bone and the
      risk of transmissible infectious from allografts and xenografts have prompted the
      search for alternative methods of achieving interbody fusion. Several of these
      methods have been associated with an unacceptable rate of complications. The
      clinical and health economic implications of the widespread introduction of
      interbody fusion devices in the absence of sound evidence cannot be ignored.
      METHODS: A systematic review of the literature relating to cervical interbody
      fusion was undertaken. Studies were assessed critically with respect to their
      methodology, results, and conclusions. RESULTS: Thirty-two clinical studies and
      10 laboratory studies were analyzed. Methodologic weaknesses were identified in
      the majority. Only four clinical reports were either randomized or blinded or
      involved independent assessment of their outcomes. Fewer than half of the studies
      included a valid statistical analysis. Radiologic evidence of fusion was limited
      in many cases. There was little evidence that nonautologous fusion devices
      offered a reduction in the length of hospital stay. Autologous bone was as
      effective as, or superior to, many other fusion devices. The early results of
      some new fusion techniques used alone or in combination showed promise.
      CONCLUSIONS: There is limited evidence supporting the use of a cervical interbody
      fusion device in place of autologous bone. There is a need to standardize the
      testing of implants with good quality laboratory work preceding clinical use.
      Certain devices including cages, some forms of hydroxyapatite, and bone
      morphogenic proteins merit further study.

PMID- 11246389
TI  - Cervical intradural disc herniation.
AB  - STUDY DESIGN: A case report of anterior en bloc resected cervical intradural disc
      herniation and a review of the literature. OBJECTIVE: To discuss the pathogenesis
      of cervical intradural disc herniation. SUMMARY OF BACKGROUND DATA: Including
      this study case, only 17 cases of cervical intradural disc herniation have been
      reported. There have been few detailed reports concerning the pathogenesis of
      cervical intradural disc herniation. METHODS: A cervical intradural disc
      herniation at C6-C7, with localized hypertrophy and segmentally ossified
      posterior longitudinal ligament, is reported in a 45-year-old man who had Brown
      Sequard syndrome diagnosed on neurologic examination. Neuroradiologic, operative,
      and histologic findings, particularly the pathology of the anterior en bloc
      resected posterior vertebral portion of C6 and C7, were evaluated for discussion
      of the pathogenesis. RESULTS: Adhesion of dura mater and hypertrophic posterior
      longitudinal ligament was observed around a perforated portion of the herniated
      disc, and histologic study showed irregularity in fiber alignment accompanied by
      scattered inflammatory cell infiltration and hypertrophy in the posterior
      longitudinal ligament. The cervical intradural disc herniation was removed
      successfully and followed by C5-Th1 anterior interbody fusion with fibular strut
      graft. Neurologic recovery was complete except for minor residual sensory
      disturbance in the leg 7 years after the surgery. CONCLUSIONS: Cervical
      intradural disc herniation is an extremely rare condition. The pathogenesis
      remains obscure. Only 16 cases have been reported in the literature, and there
      has been little discussion concerning the local pathology of the herniated
      portion. The pathogenesis of the disease in the patient reported here was
      considered to be the adhesion and fragility of dura mater and posterior
      longitudinal ligament. This was caused by hypertrophy, with chronic inflammation
      and ossification of the posterior longitudinal ligament sustaining chronic
      mechanical irritation to the dura mater, leading to perforation of the herniated
      disc by an accidental force.

PMID- 11246390
TI  - Transarticular screw fixation for atlanto-occipital dislocation.
AB  - STUDY DESIGN: A case report of traumatic atlanto-occipital dislocation managed by
      transarticular screw fixation. OBJECTIVES: To present a case with initial failed
      wire fixation but successful reduction and fixation with transarticular screw
      fixation and occipitocervical plate stabilization. SUMMARY OF BACKGROUND DATA:
      Atlanto-occipital dislocation is generally a fatal injury, except when it occurs
      in children. Management of this injury is difficult because of multidirectional
      instability and the problems associated with technical stabilization. METHODS:
      Intraoperative atlanto-occipital reduction was achieved and maintained by direct
      C0-C1 transarticular screw fixation. To protect this fixation, a posterior
      occipitocervical fusion at C0-C2 using a Y-plate was performed. RESULTS: The
      internal fixation and reduction were maintained, indicating a good surgical
      outcome, at examination 2 years after surgery. The initially severe neurologic
      deficit was reduced to some motor weakness of the right hand and weakness of
      oculomotor function. CONCLUSIONS: Anatomic reduction and reliable fixation with
      transarticular screws may provide satisfactory clinical results with important
      neurologic recovery in cases of atlanto-occipital dislocation.

PMID- 11246391
TI  - Traumatic T9 burst fracture in an 8-month-old infant: incomplete neurologic
      deficit and its recovery.
AB  - STUDY DESIGN: Case report of a rare burst fracture of the ninth thoracic vertebra
      in an 8-month-old male infant. OBJECTIVES: To describe a rare traumatic lesion in
      an infant. SUMMARY OF BACKGROUND DATA: There are two reported cases of fracture
      dislocation in an infant in the literature, both of which were managed
      surgically. However, this is the first reported clinical case of burst fracture
      in an infant. METHODS: The patient was treated conservatively and observed for 40
      months. His spine was examined by using roentgenography and magnetic resonance
      imaging. His neurologic condition was evaluated by clinical examination and
      somatosensory-evoked potential (SEP). RESULTS: The infant became ambulant with no
      need for support 2 years after injury. At that time, the burst vertebra was
      remodeling gradually and showed no spinal deformity. CONCLUSION: Fracture
      dislocation of the spine with neurologic deficit requires surgical management.
      However, burst fracture can be managed conservatively, provided the neurologic
      condition improves.

PMID- 11246394
TI  - Load-sharing between anterior and posterior elements in a lumbar motion segment
      implanted with an artificial disc.
AB  - STUDY DESIGN: A nonlinear three-dimensional finite element model of the
      osteoligamentous L3-L4 motion segment was used to predict changes in posterior
      element loads as a function of disc implantation and associated surgical
      procedures. OBJECTIVES: To evaluate the effects of disc implantation on the
      biomechanics of the posterior spinal elements (including the facet joints,
      pedicles, and lamina) and on the vertebral bodies. SUMMARY OF BACKGROUND DATA:
      Although several artificial disc designs have been used clinically, biomechanical
      data-particularly the change in loads in the posterior elements after disc
      implantation-are sparse. METHODS: A previously validated intact finite element
      model was implanted with a ball-and-cup-type artificial disc model via an
      anterior approach. The implanted model predictions were compared with in vitro
      data. To study surgical variables, small and large windows were cut into the
      anulus, and the implant was placed anteriorly and posteriorly within the disc
      space. The anterior longitudinal ligament was also restored. Models were
      subjected to either 800 N axial compression force alone or to a combination of 10
      N-m flexion-extension moment and 400 N axial preload. Implanted model predictions
      were compared with those of the intact model. RESULTS: Facet loads were more
      sensitive to the anteroposterior location of the artificial disc than to the
      amount of anulus removed. Under 800 N axial compression, implanted models with an
      anteriorly placed artificial disc exhibited facet loads 2.5 times greater than
      loads observed with the intact model, whereas posteriorly implanted models
      predicted no facet loads in compression. Implanted models with a posteriorly
      placed disc exhibited greater flexibility than the intact and implanted models
      with anteriorly placed discs. Restoration of the anterior longitudinal ligament
      reduced pedicle stresses, facet loads, and extension rotation to nearly intact
      levels. CONCLUSIONS: The models suggest that, by altering placement of the
      artificial disc in the anteroposterior direction, a surgeon can modulate motion
      segment flexuralstiffness and posterior load-sharing, even though the specific
      disc replacement design has no inherent rotational stiffness.

PMID- 11246393
TI  - A functional subdivision of hip, abdominal, and back muscles during asymmetric
      lifting.
AB  - STUDY DESIGN: An experimental study of muscle recruitment patterns during
      asymmetric lifting in healthy individuals. OBJECTIVE: To investigate muscle
      recruitment patterns during asymmetric lifting, representing a common daily
      living activity, to determine whether systematic differences exist between
      functioning of the local and global muscle systems. SUMMARY OF BACKGROUND DATA:
      The normal function of the local muscle system is to provide sufficient segmental
      stability to the spine. The global muscle system provides general trunk
      stabilization and enables the static and dynamic work necessary for daily living
      and sports activities. Current knowledge about these two muscle groups appears to
      be specifically derived from anatomic findings and experiments conducted under
      artificial circumstances. To the authors' knowledge, the recruitment patterns of
      both muscle groups have not been investigated in daily living activities.
      METHODS: Twenty-nine healthy individuals performed different variants of
      asymmetric lifting activities. Electromyographic data were collected from seven
      hip, abdominal, and back muscle pairs. In addition, trunk kinematics were
      measured by means of an ultrasonic movement analysis system. RESULTS: The left
      and right obliquus internus, rectus femoris, and multifidus showed symmetric co
      contraction in all variants of activities. In contrast, significant left/right
      differences were observed in the external oblique, gluteus maximus, iliocostalis
      lumborum pars thoracis, and latissimus dorsi. CONCLUSIONS: The results of this
      study show a symmetric activation of the local muscles during the performance of
      low-load, asymmetric lifting tasks, which suggests that these muscles play a
      stabilizing role during these manoeuvres. The global muscles, however, hand show
      asymmetric patterns of activation during the same tasks, supporting their role as
      global stabilizers and prime movers.

PMID- 11246395
TI  - Combined laminectomy and thoracoscopic resection of dumbbell-type thoracic cord
      tumor.
AB  - STUDY DESIGN: A study of five patients whose dumbbell or paraspinal tumors of the
      thoracic spine were managed by using thoracoscopic surgery is reported.
      OBJECTIVES: To report on the use of combined laminectomy and thoracoscopic
      resection for the management of dumbbell-type thoracic cord tumor. SUMMARY OF
      BACKGROUND DATA: Some posterior mediastinal tumors can be resected safely with
      video-assisted thoracic surgery. However, there are few reports on thoracoscopic
      resection of dumbbell and paraspinal tumors of the thoracic spine. METHODS: Five
      patients who received treatment for thoracic spine dumbbell tumors and paraspinal
      tumors were studied retrospectively. Three patients had dumbbell tumors, and two
      had paraspinal tumors of the thoracic spine. Preoperative evaluation of each
      patient included plain chest radiography, magnetic resonance imaging, and
      computed tomography. All patients underwent total resection by means of a
      combined posteroanterior approach, with thoracoscopic surgery for dumbbell tumors
      and thoracoscopic surgery alone for paraspinal tumors. In all patients, a gross
      total resection was achieved with this approach. All patients were observed for a
      minimum of 3 years. RESULTS: All patients regained their ability to walk 2 days
      after surgery, except for one patient who had a hemothorax. A gross total tumor
      resection, documented by magnetic resonance imaging, was performed on all
      patients. Follow-up imaging at 6 weeks, 1 year, 2 years, and 3 years after
      surgery did not show residual tumor or recurrence in any patient. To date, spinal
      instability has not developed in any patient. CONCLUSIONS: Combined laminectomy
      and thoracoscopic surgery may be a good alternative method for managing thoracic
      dumbbell tumors.

PMID- 11246397
TI  - Fenestration of the extracranial vertebral artery: review of the literature.
AB  - STUDY DESIGN: A case report on fenestration of the extracranial vertebral artery
      found at forensic autopsy. OBJECTIVE: To describe an extracranial vertebral
      artery fenestration involving the subaxial cervical region, assessed
      radiographically and angiographically at forensic autopsy, in a young man.
      SUMMARY OF BACKGROUND DATA: Duplications or fenestrations of the extracranial
      course of the vertebral artery are rare and seen almost exclusively as a
      coincidental finding in angiographic studies. The terms "fenestration" and
      "duplication" are often incorrectly used synonymously. The former describes the
      passage of the duplicated vessel within the vertebral foramen transversarium,
      whereas the latter refers to the duplicated vessel coursing additionally through
      the spinal canal. The reported cases describing duplication are more common. Only
      three cases of vertebral extracranial fenestrations, involving only the upper
      cervical spinal segments, have been described in the literature. RESULTS:
      Angiography showed a fenestration of the vertebral artery localized between the
      intervertebral spaces of C2-C3 and C3-C4. At dissection, the vertebral artery
      appeared as a single vessel in the area of the fenestration. Histologically, a
      distinct difference in the thickness and composition of the vessel walls was
      found between the two vessel trunks. At autopsy, no further anomalies were
      observed in the vessels supplying the brain, which is contrary to the commonly
      held belief that fenestration is frequently associated with vascular
      malformations. CONCLUSION: Fenestration of the extracranial course of the
      vertebral artery is a developmental or congenital anomaly. A review of the
      literature demonstrated that this is apparently only a coincidental finding and
      has no pathologic significance.

PMID- 11246399
TI  - Fast Algorithm for X-ray Cone-beam Microtomography.
AB  - Cone-beam X-ray microtomography attracts increasing attention due to its
      applications in biomedical sciences, material engineering, and industrial
      nondestructive evaluation. Rapid volumetric image reconstruction is highly
      desirable in all these areas for prompt visualization and analysis of complex
      structures of interest. In this article, we reformulate a generalized Feldkamp
      cone-beam image reconstruction algorithm, utilize curved voxels and mapping
      tables, improve the reconstruction efficiency by an order of magnitude relative
      to a direct implementation of the standard algorithm, and demonstrate the
      feasibility with numerical simulation and experiments using a prototype cone-beam
      X-ray microtomographic system. Our fast algorithm reconstructs a 256-voxel cube
      from 100 projections within 2 min on an Intel Pentium II(R) 233 MHz personal
      computer, produces satisfactory image quality, and can be further accelerated
      using special hardware and/or parallel processing techniques.

PMID- 11246396
TI  - Iliopsoas hematoma with femoral neuropathy presenting a diagnostic dilemma after
      spinal decompression.
AB  - STUDY DESIGN: Case report of an iliopsoas hematoma with femoral neuropathy
      appearing 8 weeks after a posterior spinal decompression procedure. OBJECTIVES:
      To describe a potential complication and differential diagnosis for nerve root
      symptoms following spinal decompression. SUMMARY OF BACKGROUND DATA: Iliopsoas
      hematoma is usually a complication of anticoagulation, hemophilia, or trauma. It
      has not been described previously as a complication of posterior spinal
      decompression. Femoral neuropathy results from compression within the iliopsoas
      compartment. METHODS: A 53-year-old woman reported pain in the right side of her
      groin and an increasing fixed flexion deformity of the right hip 8 weeks after a
      posterior, midline, spinal decompression. A femoral neuropathy later developed.
      Magnetic resonance imaging and computed tomography were performed. RESULTS:
      Imaging studies demonstrated a diffusely enlarged iliopsoas. Exploration revealed
      a large hematoma, which was evacuated. The compartment was fully decompressed
      with resolution of the nerve root symptoms within 48 hours. CONCLUSIONS:
      Iliopsoas pathology is a rare cause of nerve root symptoms and presented
      diagnostic difficulties after an apparently successful spinal decompression.

PMID- 11246400
TI  - Advances in Atom Probe Specimen Fabrication from Planar Multilayer Thin Film
      Structures.
AB  - A sample preparation method has been developed whereby sharp needle-shaped
      specimens for atom probe analysis are fabricated from multilayer thin films
      deposited onto silicon substrates. The specimens are fabricated in an orientation
      such that atom probe composition profiles across the layer interfaces can be
      determined with atomic-layer spatial resolution, i.e., the layer normals are
      parallel to the needle axis. The method uses standard silicon etching techniques
      and focused ion-beam milling. The feasibility and utility of this technique are
      shown through its application to a NiFe/CoFe/Cu/CoFe-based thin film structure.

PMID- 11246401
TI  - Force Modulation Elasticity Mapping of Plastic-embedded, Thin-sectioned Skeletal
      Muscle.
AB  - We have been researching the capability of atomic force microscopy to reveal
      nontopographic properties of tissue embedded in plastic and sectioned with
      standard electron microscopic techniques. We present topography and elasticity
      maps of plastic-embedded, thin sections of muscle tissue. The images show
      topography correlated with the normal repeating structure of the sarcomere.
      Elasticity mapping using force modulation revealed contrast between the actin-
      and myosin-rich areas. We attribute the observed contrast in elasticity to the
      difference in local concentrations of biological material in embedding plastic.

PMID- 11246402
TI  - Morphometrical Method for Estimating Mean Cell Volume of Phagocytosing Cells.
AB  - A method is described for the estimation of mean cell volume of phagocytosing
      cells. The cells are coembedded with yeast particles of known size. By
      combination of data obtained from morphometrical analysis of sections in both the
      light and transmission electron microscopes, an estimate of the ratio between
      cell volume and yeast particle volume is obtained. The method makes use of the
      dissector but does not require measurements on serial sections or knowledge of
      section thickness. Evaluation of the method was done by studying the effect of
      phagocytosis of latex beads on macrophage cell volume and surface area. It was
      found that the surface area of phagocytosing macrophages remained constant
      although the cell volume increased by 27%. Furthermore, in phagocytosing
      macrophages, the amount of membrane enclosing intracellular vacuoles decreased by
      28%, but this loss of membrane was balanced by the appearance of membrane
      enclosing the phagocytosed latex beads. The method described here may prove
      useful for morphometrical studies on phagocytosing leukocytes, as well as on
      intracellular parasites located within these cells.

PMID- 11246403
TI  - Extracellular Adenosine Triphosphate Triggers Arrhythmias and Elemental
      Redistribution in Electrically Stimulated Rat Cardiac Myocytes.
AB  - An increase in extracellular adenosine triphosphate (ATP) is arrhythmogenic in
      rat cardiac myocytes and extracellular ATP levels are elevated during cardiac
      ischemia. To gain insight into the mechanism by which the arrhythmic contractions
      are generated, we investigated changes in subcellular elemental content by
      electron probe microanalysis (EPMA) in isolated adult rat cardiac myocytes
      stimulated by the ATP analog, 2-methylthio-ATP (2-M-S-ATP). We also measured the
      effects of 2-M-S-ATP stimulation on myocyte cell shortening. In electrically
      stimulated myocytes, 2-M-S-ATP stimulation generated arrhythmic contractions and
      also increased the amplitude of cell shortening. However, only the arrhythmic
      contractions were reversed by 2-M-S-ATP washout. EPMA of freeze-dried
      cryosections of rapidly frozen 2-M-S-ATP-stimulated myocytes showed increased
      cytosolic Na and Cl, decreased K, but no significant change in mitochondrial Ca
      upon 2-M-S-ATP stimulation. The arrhythmias were abolished upon 2-M-S-ATP
      washout, and the observed changes in cytosolic elemental content also reversed
      upon agonist washout, thus suggesting that the increased Na and Cl, and decreased
      K, are specifically associated with the ATP-dependent spontaneous contractile
      activity. The observed increase in intracellular Na upon 2-M-S-ATP stimulation
      may explain our observation of prolonged relaxation time of 2-M-S-ATP-stimulated
      contractions. This may be due to inhibition of Ca(2+) efflux via the Na(+) Ca(2+)
      exchanger.

PMID- 11246404
TI  - Cardiac Defects Associated with the Absence of the Platelet-derived Growth Factor
      alpha Receptor in the Patch Mouse.
AB  - In this report, we describe the distribution of the platelet-derived growth
      factor receptor alpha (PDGFRalpha) by immunolocalization in the embryonic day
      10.5 mouse heart and defects in heart development associated with the absence of
      this receptor in the Patch mouse. The Patch mouse is a naturally occurring mutant
      that has been accepted as a model for determining the role of the PDGFRalpha in
      early cardiac development. Even though other genetic defects exist in this
      naturally occurring mutant, most defects associated with cardiac development are
      believed to be a result of the absence of this receptor. Gross morphological
      defects including improper septation of the outflow tract, dysmorphic shape of
      the heart, and lack of trabecular development are similar to those that have been
      previously described. Many of these defects have been attributed to the failure
      of a subset of non-neuronal neural crest cells to properly migrate into the
      region of the developing outflow tract. In these studies, we have also used
      confocal scanning laser and transmission electron microscopy to describe and
      compare the organization and differentiation of the cytoskeletal proteins actin
      and myosin in littermate control and Patch mouse hearts. Cytoskeletal
      organization of the cardiac myocytes in Patch mouse hearts has not previously
      been described. In most cardiac myocytes of Patch mice, actin was found only on
      the periphery of the cells, and the organization of actin, myosin, and precursor
      Z-band material into distinct myofibrils was greatly reduced.

PMID- 11246405
TI  - News and Commentary.

PMID- 11246406
TI  - Isolation and Characterization of Microsatellite Loci for Striped Bass (Morone
      saxatilis).
AB  - Genetic variation has been difficult to detect in striped bass (Morone
      saxatilis). Therefore, we identified and characterized 13 microsatellite loci to
      provide additional genetic markers for striped bass. Microsatellites were
      identified by screening a striped bass genomic library or by using primers
      developed for European sea bass (Dicentrarchus labrax) microsatellite loci. We
      found that 6 of the 13 microsatellite loci were polymorphic in DNA samples
      obtained from wild populations of striped bass. The number of alleles per locus
      varied from 3 to 12, and the observed heterozygosities ranged from 0.55 to 0.78.
      These results indicate that microsatellite loci provide more alleles and higher
      heterozygosities than other genetic markers developed for striped bass.

PMID- 11246407
TI  - Complementary DNA Cloning and Characterization of Pearlin, a New Class of Matrix
      Protein in the Nacreous Layer of Oyster Pearls.
AB  - Calcified shell layer is composed of two polymorphs of CaCO(3), aragonite or
      calcite, and an organic matrix. The organic matrix consists of EDTA-soluble and
      insoluble fractions. These fractions are thought to regulate the formation of the
      elaborate shell structure. After decalcification of powdered pearl with 0.3 M
      EDTA, an EDTA-insoluble fraction was extracted with 0.3 M EDTA/8 M urea. This
      extraction step enabled us to purify a new class of EDTA-insoluble protein,
      Pearlin, almost homogeneously. Pearlin has a molecular weight of about 15 kDa and
      contains a sulfated mucopolysaccharide. We cloned the complementary DNA coding
      for Pearlin and deduced its complete amino acid sequence. Sequence analysis
      reveals that Pearlin is composed of 129 amino acids with a high proportion of Gly
      (10.8%), Tyr (10.0%), Cys (8.5%), Asn (7.7%), Asp (7.7%), and Arg (7.7%).
      Northern blot analysis showed that Pearlin messenger RNA was expressed
      specifically in mantle epithelium. From the sequencing data, Pearlin was shown to
      be quite different from the fibrous protein rich in Ala and Gly. The function of
      this protein in biomineralization is discussed.

PMID- 11246408
TI  - Sequence of the Small Subunit Ribosomal RNA Gene of Perkinsus atlanticus-like
      Isolated from Carpet Shell Clam in Galicia, Spain.
AB  - Parasites identified as Perkinsus atlanticus have been reported infecting carpet
      shell clams in Galicia (northwest Spain). We have sequenced the 18S ribosomal RNA
      gene of in vitro cultured Perkinsus atlanticus-like or hypnospores from diseased
      clams, and compared it with the same genomic region from P. marinus and Perkinsus
      sp. We have also compared the sequence of internal transcribed spacer (ITS) 1,
      ITS 2, and 5.8S rRNA from our isolate with the P. atlanticus GenBank sequence.
      The phylogenetic analysis of our cultured parasite based on the 18S gene led us
      to conclude that this isolate is not related to the genus Perkinsus but to the
      protists Anurofeca, Ichthyophonus, and Psorospermium, located near the animal
      fungal divergence. These last two genera have been included, together with
      Dermocystidium, in the newly described DRIPs (Dermocystidium, rossete agent,
      Ichthyophonus, and Psorospermium) clade, recently named Mesomycetozoa.

PMID- 11246409
TI  - Diel Patterns of Regulation of rbcL Transcription in a Cyanobacterium and a
      Prymnesiophyte.
AB  - Diel patterns of rbcL transcription, ribulose-1,5-bisphosphate
      carboxylase/oxygenase (RubisCO) activity, and whole cell carbon fixation were
      compared in the marine cyanobacterium Synechococcus PCC7002 and the chromophytic
      prymnesiophyte Pavlova gyrans. Both organisms were grown on a 12:12 light-dark
      cycle, with the light period starting at 0700. Strong diel patterns in these
      three aspects of carbon fixation occurred in both organisms, with maximal levels
      in the light period and minima in the dark. In Synechococcus, maximal rbcL
      transcript abundance occurred at noon and was followed by rapid disappearance.
      RubisCO enzyme activity and whole cell carbon fixation were elevated at 1600, and
      they disappeared over the next 8 hours. In contrast, in Pavlova, rbcL transcript
      abundance was maximal at 1600, and it was maintained at 66% of this level into
      the dark period (2000). Whole cell carbon fixation and RubisCO activity were
      elevated into the dark period (at 2000), being 77% and 81%, respectively, of the
      maximum. A similar diel pattern of cyanobacterial-like and chromophyte-like rbcL
      transcription has been observed in natural phytoplankton populations. These
      studies suggest that chromophytes are more adapted to take advantage of carbon
      fixation late in the day than cyanophytes.

PMID- 11246410
TI  - Linkage Relationships and Haplotype Variation of the Major Histocompatibility
      Complex Class I A Genes in the Cichlid Fish Oreochromis niloticus.
AB  - The haplochromine cichlid species flocks of the East African Great Lakes are one
      of the best examples of adaptive radiation. Analysis of genetic variation among
      these species provides valuable information on species relationships and timing
      of speciation events. Although the haplochromine cichlids generally display
      little genetic variation, the major histocompatibility complex (Mhc) genes have
      been found to be highly variable. A study of the linkage relationships of the Mhc
      class I A genes in the cichlid fish Oreochromis niloticus was therefore
      undertaken. Class I loci were identified, and their segregation in seven mothers
      and their haploid embryos was determined. In total, 56 class I A sequences were
      found among the seven families. A strong concordance of segregation was observed
      in five haplotypes among the embryos, indicating a close linkage of all loci. The
      number of loci per haplotype varied from 11 to 17, while the total number of
      distinct loci found among all families was 22. These findings show that all class
      I A loci are linked in a single genetic cluster in O. niloticus.

PMID- 11246411
TI  - Comparison of Four Mendelian Loci of the California Sea Hare (Aplysia
      californica) from Populations of the Coast of California and the Sea of Cortez.
AB  - Aplysia californica is a species widely used in neurobiology, and specimens are
      collected from a wide range of places along its distribution range. A.
      californica is endemic to the coast of California and the Gulf of California. On
      the west coast, this is an unusual distribution range relative to other benthic
      species from that region. Four polymorphic nuclear Mendelian markers were
      identified (three single-copy nuclear DNA loci and one microsatellite) for an
      initial survey of genetic variation of wild populations. F(ST) values not
      significantly different from 0 (overall F(ST) = 0.0148) suggest there was no
      geographic genetic population subdivision in 177 individuals examined.

PMID- 11246412
TI  - Use of Competitive PCR to Detect and Quantify Haplosporidium nelsoni Infection
      (MSX disease) in the Eastern Oyster (Crassostrea virginica).
AB  - This study was undertaken to develop a quantitative polymerase chain reaction
      assay that would improve the utility of PCR for detecting Haplosporidium nelsoni
      (MSX), a serious parasite of the eastern oyster Crassostrea virginica. A
      competitive PCR sequence was generated from the H. nelsoni small subunit
      ribosomal DNA fragment, originally described by Stokes and colleagues, that was
      amplified by the same PCR primers and had similar amplification performance.
      Assays performed using competitor dilutions ranging from 0.05 to 500 pg/ul DNA
      were used to test oyster samples designated using histological techniques as
      having "light" or "heavy" MSX infections. Visual diagnoses were confirmed equally
      well with three methods: densitometry of ethidium-bromide-stained agarose,
      densitometry of SYBRGreen-stained polyacrylamide gels, and analysis by GeneScan
      3.0 of fluorescent products detected in ultrathin gels. Oysters diagnosed as
      negative for MSX tested as negative or light by PCR. Oysters with light MSX
      infections generally had less than 5 pg/ul infectious DNA. Oysters with heavy
      infections generally corresponded to 5 pg/ul or greater competitor dilutions.

PMID- 11246413
TI  - Triploid and Tetraploid Zhikong Scallop, Chlamys farreri Jones et Preston,
      Produced by Inhibiting Polar Body I.
AB  - Triploid scallops are valuable for aquaculture because of their enlarged adductor
      muscle, and tetraploids are important for the commercial production of triploids.
      We tested tetraploid induction in the zhikong scallop by inhibiting polar body I
      in newly fertilized eggs. The ploidy of resultant embryos was determined by
      chromosome counting at 2- to 4-cell stage and by flow cytometry thereafter.
      Embryos from the control groups were mostly diploids (79%), along with some
      aneuploids. Embryos from the treated groups were 13% diploids, 18% triploids, 26%
      tetraploids, 13% pentaploids, and 36% aneuploids. Tetraploids, pentaploids, and
      most aneuploids suffered heavy mortality during the first week and became
      undetectable among the larvae at day 14. Five tetraploids (2%) were found among a
      sample of 267 spat from one of the replicates, and none was detected at day 450.
      The adductor muscle of triploid scallops was 44% heavier (P <.01) than that of
      diploids, confirming the value of the triploid technology in this species.

PMID- 11246414
TI  - Development of Species-Specific Markers of the Tropical Oyster (Crassostrea
      belcheri) in Thailand.
AB  - Randomly amplified polymorphic DNA (RAPD) analysis was used to identify species
      specific markers of 5 oyster species in Thailand: Crassostrea belcheri,
      Crassostrea iredalei, Saccostrea cucullata, Saccostrea forskali, and Striostrea
      (Parastriostrea) mytiloides. Species-specific markers were found in C. belcheri,
      C. iredalei, and S. cucullata but not in S. forskali and S. mytiloides. Three C.
      belcheri-specific RAPD fragments were cloned and sequenced. A primer set was
      designed from each of the recombinant clones (pPACB1, pPACB2, and pPACB3). The
      polymerase chain reaction products showed expected sizes of 536, 600, and 500 bp,
      respectively, with the sensitivity of detection approximately 30 pg of C.
      belcheri total DNA template. The specificity of pPACB1 was examined against 135
      individuals of indigenous oyster species in Thailand and against outgroup
      references S. commercialis (N = 12) and Perna viridis (N = 12). Results indicated
      the species-specific nature of primers developed from pPACB1. This primer set can
      be used for broodstock selection and determination of C. belcheri larvae to
      assist the selective breeding program for this commercially important species.

PMID- 11246415
TI  - Synthesis of Hemolymph High-Density Lipoprotein beta-Glucan Binding Protein by
      Penaeus vannamei Shrimp Hepatopancreas.
AB  - It was recently shown that the shrimp high-density lipoprotein (HDL) and the beta
      1,3-glucan binding protein (BGBP) are identical, implying dual functions for the
      same protein: lipid transport and involvement in the defense system. Because this
      protein is present in plasma, and the hepatopancreas is a major lipid storage
      gland, we investigated the presence of the HDL/BGBP polypeptide and its messenger
      RNA in this tissue using a monospecific antibody against HDL/BGBP. Hepatopancreas
      crude protein extracts, as well as polypeptides produced by poly(A)(+) RNA in
      vitro translation, were recognized by the anti-HDL/BGBP. Furthermore, a specific
      pattern was revealed in hepatopancreas thin sections by immunodetection. Strong
      recognition was seen in the epithelial cells of hepatopancreatic tubules,
      probably related to the secretion process of this protein.

PMID- 11246416
TI  - Expressed Sequence Tag Analysis of Kidney and Gill Tissues from Rainbow Trout
      (Oncorhynchus mykiss) Infected with Infectious Hematopoietic Necrosis Virus.
AB  - Expressed sequence tags (ESTs) were obtained from the kidney and gill tissues of
      rainbow trout, Oncorhynchus mykiss, infected with infectious hematopoietic
      necrosis virus (IHNV). The results of single-pass sequencing of ESTs from 198
      clones (AU081027-AU081192) from kidney complementary DNA and 45 clones (AU081193
      AU081236) from gill cDNA are reported herein. Sequences of the cDNA clones were
      compared with sequences in the GenBank database. Fourteen clones (20%) appeared
      to be completely unknown and may represent newly described genes, whereas 158
      clones (80%) were identified on the basis of matches to sequences in the
      database. Three of the unidentified sequences were isolated from both the kidney
      and the gill cDNA libraries. However, no sequences were identical between kidney
      and gill clones.

PMID- 11246417
TI  - Tropomyosin Is the Major Mollusk Allergen: Reverse Transcriptase Polymerase Chain
      Reaction, Expression and IgE Reactivity.
AB  - The complementary DNAs encoding tropomyosins of the abalone Haliotis
      diversicolor, the scallop Chlamys nobilis, and the mussel Perna viridis were
      amplified by reverse transcriptase polymerase chain reaction and thereafter
      cloned in plasmid vectors for expression. Immunoblot analysis showed that
      recombinant proteins of abalone, scallop, and mussel tropomyosin were reactive to
      serum IgE antibodies from subjects allergic to shellfish but not to nonallergic
      controls. Nucleotide and amino acid sequences of abalone, scallop, and mussel
      tropomyosins are highly similar (mostly > 55%) to those of crustacean allergens
      identified as tropomyosins. Absorption experiments showed that recombinant
      tropomyosins from the 3 mollusks were able to remove serum IgE reactivity against
      the 38-kDa tropomyosin of the organisms. These results demonstrate that
      tropomyosin is the major allergen among various common edible mollusks. Yet a
      comparison between the amino acid sequences of putative epitopes in crustaceans
      and mollusks suggests that the epitopes in the two groups may be distinct.
      Parsimony analysis of the nucleotide sequences of tropomyosin from different
      mollusks suggests that the tropomyosin gene sequence is a useful tool for
      phylogenetic analysis of this group of animals.

PMID- 11246418
TI  - Structure and function of mitochondrial anion transport proteins.

PMID- 11246419
TI  - Role of pre-epithelial "unstirred" layers in absorption of nutrients from the
      human jejunum.
AB  - Pre-epithelial "unstirred" layers (abbr. pL) are generally regarded as
      undesirable diffusion barriers that impede access to absorptive cells of
      exogenous hexoses, amino acids or other experimental probes added to fluids
      bathing the mucosal surface. In the present paper it is suggested that the pL may
      have a functional role. Diffusion plus convection of saccharides and
      oligopeptides from lumen to brush border, combined with absorption to blood of
      their hydrolytic products, confers rectifying properties to the pL. The proposed
      model, based on experimental data from segmental jejunal perfusions in normal
      human subjects, indicates that the functional pathway for diffusion plus
      convection through the pL of hexoses and amino acids bound in the form of
      oligomers is only 10 +/- 2 microm or little more than the anatomical thickness of
      the glycocalyx and mucus layers. In contrast, the pathlength from brush border to
      lumenal perfusion fluid for diffusion minus convection of monomers generated by
      membrane bound hydrolases is 50-150 microm. According to this model the pL offers
      little resistance to the passage of saccharides or oligopeptides from lumen to
      brush border but at the same time it provides a protective blanket that
      diminishes diffusional losses to lumenal chyme of hexoses and amino acids
      generated in the brush border. The model provides a theoretical explanation for
      the "kinetic advantage" of transporting hexoses or amino acids through the pL in
      the form of oligomers and it predicts the proximal-distal concentrations of free
      glucose or fructose found experimentally in the outflows from jejunal segments
      perfused with sucrose or maltose.

PMID- 11246420
TI  - Complex effects of papain on function and inhibitor sensitivity of the red cell
      anion exchanger AE1 suggest the presence of different transport subsites.
AB  - Band 3 (AE1), the anion exchanger of the human erythrocyte membrane, mediates not
      only fluxes of small hydrophilic anions (e.g., chloride, oxalate), but also the
      flip-flop of long-chain amphiphilic anions (e.g., dodecylsulfate). Treatment of
      erythrocytes with papain, long known to inhibit the transport of the former type
      of anions, accelerates the transport of the latter type. In an attempt to
      elucidate the basis of these opposite responses to papain, several small
      amphiphilic arylalkyl sulfonates and -sulfates were tested for the response of
      their transport, via AE1, to papain. Although all these probes are most likely
      transported by a flux and not by flip-flop, their transport was inhibited by
      papain only in some cases, but accelerated in others. Different responses to
      papain therefore most likely do not reflect differences between transport by flux
      or by flip. The transports of different species of anions also differed
      considerably in the changes of their sensitivity, to noncovalent and some
      covalent inhibitors, brought about by papain treatment. While oxalate transport
      remained as sensitive as in native cells, transports of small amphiphilic anions
      lost their sensitivity to a major extent, regardless of the inhibition or
      acceleration of their transport by papain. The results are discussed in the light
      of present concepts of the structural organisation of AE1, and interpreted in
      terms of a model of different transport subsites for different species of anions
      in this transporter.

PMID- 11246421
TI  - Two-step mechanism of phlorizin binding to the SGLT1 protein in the kidney.
AB  - The relationships between phlorizin binding and Na+-glucose cotransport were
      addressed in rabbit renal brush-border membrane vesicles. At pH 6.0 and 8.6, high
      affinity phlorizin binding followed single exponential kinetics. With regard to
      phlorizin concentrations, the binding data conformed to simple Scatchard kinetics
      with lower apparent affinities of onset binding (Kdi = 12-30 microM) compared to
      steady-state binding (Kde = 2-5 microM), and the first-order rate constants
      demonstrated a Michaelis-Menten type of dependence with Km values identical to
      Kdi. Phlorizin dissociation from its receptor sites also followed single
      exponential kinetics with time constants insensitive to saturating concentrations
      of unlabeled phlorizin or D-glucose, but directly proportional to Na+
      concentrations. These results prove compatible with homogeneous binding to SGLT1
      whereby fast Na+ and phlorizin addition on the protein is followed by a slow
      conformation change preceding further Na+ attachment, thus occluding part of the
      phlorizin-bound receptor complexes. This two-step mechanism of inhibitor binding
      invalidates the recruitment concept as a possible explanation of the fast-acting
      slow-binding paradigm of phlorizin, which can otherwise be resolved as follows:
      the rapid formation of an initial collision complex explains the fast-acting
      behavior of phlorizin with regard to its inhibition of glucose transport;
      however, because this complex also rapidly dissociates in a rapid filtration
      assay, the slow kinetics of phlorizin binding are only apparent and reflect its
      slow isomerization into more stable forms.

PMID- 11246422
TI  - Ni2+ slows the activation kinetics of high-voltage-activated Ca2+ currents in
      cortical neurons: evidence for a mechanism of action independent of channel-pore
      block.
AB  - The effects of Ni2+ were evaluated on slowly-decaying, high-voltage-activated
      (HVA) Ca2+ currents expressed by pyramidal neurons acutely dissociated from
      guinea-pig piriform cortex. Whole-cell, patch-clamp recordings were performed
      with Ba2+ as the charge carrier. Ni2+ blocked HVA Ba2+ currents (IBas) with an
      EC50 of approximately 60 microM. Additionally, after application of nonsaturating
      Ni2+ concentrations, residual currents activated with substantially slower
      kinetics than both total and Ni2+-sensitive I(Ba)s. None of the pharmacological
      components of slowly decaying, HVA currents activated with kinetics significantly
      different from that of total currents, indicating that the effect of Ni2+ on
      I(Ba)s kinetics cannot be attributed to the preferential inhibition of a fast
      activating component. The effect of Ni2+ on I(Ba) amplitude was voltage
      independent over the potential range normally explored in our experiments (-60 to
      +20 mV), hence the Ni2+-dependent decrease of I(Ba) activation rate is not due to
      a voltage- and time-dependent relief from block. Moreover, Ni2+ significantly
      reduced I(Ba) deactivation speed upon repolarization, which also is not
      compatible with a depolarization-dependent unblocking mechanism. The dependence
      on Ni2+ concentration of the I(Ba) activation-rate reduction was remarkably
      different from that found for I(Ba) block, with an EC50 of approximately 20
      microM and a Hill coefficient of approximately 1.73 vs. approximately 1.10. These
      results demonstrate that Ni2+, besides inhibiting the I(Ba)s under study probably
      by exerting a blocking action on the pore of the underlying Ca2+ channels, also
      interferes with Ca2+-channel gating kinetics, and strongly suggest that the two
      effects depend on Ni2+ occupancy of binding sites at least partly distinct.

PMID- 11246423
TI  - Ion selectivity of the cytoplasmic binding sites of the Na,K-ATPase: II.
      Competition of various cations.
AB  - In the E1 state of the Na,K-ATPase all cations present in the cytoplasm compete
      for the ion binding sites. The mutual effects of mono-, di- and trivalent cations
      were investigated by experiments with the electrochromic fluorescent dye RH421.
      Three sites with significantly different properties could be identified. The most
      unspecific binding site is able to bind all cations, independent of their valence
      and size. The large organic cation Br2-Titu3+ is bound with the highest affinity
      (<microM), among the tested divalent cations Ca2+ binds the strongest, and Na+
      binds with about the same equilibrium dissociation constant as Mg2+
      (approximately 0.8 mM). For alkali ions it exhibits binding affinities following
      the order of Rb+ approximately equals K+ > Na+ > Cs+ > Li+. The second type of
      binding site is specific for monovalent cations. its binding affinity is higher
      than that of the first type, for Na+ ions the equilibrium dissociation constant
      is < 0.01 mM. Since binding to that site is not electrogenic it has to be close
      to the cytoplasmic surface. The third site is specific for Na+, no other ions
      were found to bind, the binding is electrogenic and the equilibrium dissociation
      constant is 0.2 mM.

PMID- 11246424
TI  - CFTR activation raises extracellular pH of NIH/3T3 mouse fibroblasts and C127
      epithelial cells.
AB  - Cystic Fibrosis (CF) is caused by mutations in the gene for CFTR, a cAMP
      activated anion channel found in apical membranes of wet epithelia. Since CFTR is
      permeable to HCO3- and changes in extracellular fluid composition may contribute
      to CF lung disease, we investigated possible differences in extracellular pH
      (pHo) between CFTR-expressing and control cell lines. The Cytosensor
      Microphysiometer was used to study forskolin-stimulated extracellular
      acidification rates in CFTR-expressing and control mouse mammary epithelial
      (C127) and fibroblast (NIH/3T3) cell lines. Forskolin, which activates CFTR via
      raised cAMP, caused decreased extracellular acidification of CFTR-expressing
      NIH/3T3 and C127 cells by 15-35%. By contrast, forskolin caused increased
      extracellular acidification of control cells by 10-20%. Ionomycin, which may
      activate CFTR via PKC, also elicited this decreased extracellular acidification
      signal only in cells expressing CFTR. In control experiments, dideoxyforskolin
      had no effect on the acidification rates and osmotic stimuli were shown to
      equally stimulate all cell lines. These results suggest a role for CFTR in
      controlling pHo and complement recent evidence that HCO3- dependent epithelial
      secretion may be reduced in amount and altered in composition in CF.

PMID- 11246425
TI  - Comparative evaluation of traditional, ultrasonic, and pneumatic assisted
      lipoplasty: analysis of local and systemic effects, efficacy, and costs of these
      methods.
AB  - Recently ultrasound assisted liposuction (UAL) and pneumatic assisted liposuction
      (PAL) have been introduced as an attempt to improve the results and reduce the
      pitfalls of standard liposuction (SAL). Until now no studies comparing, at the
      same time, UAL, PAL, and SAL have been published. The aim of this study was to
      analyze these methods from the surgeon's point of view, focusing not only on
      aesthetic results but also on local and systemic trauma, efficacy, handling, and
      cost. Forty-five cosmetic patients affected by local lipodystrophy, divided into
      three equal groups, have undergone liposuction with the three above-mentioned
      techniques. Quantitative and qualitative analysis of lipoaspirates, together with
      blood chemistry, local and systemic complications, time to aspirate 100 cm3,
      distress, fatigue, and costs of the procedures, has been recorded. Our results
      showed bloodier lipoaspirates in SAL and a higher percentage of triglycerides in
      UAL lipoaspirates. Blood tests revealed a slight decrease in the postoperative Hb
      in SAL only. Early complications observed were four erythemas in PAL, three
      ecchymoses in SAL, and one long-lasting edema in UAL. Aesthetic results rated by
      independent viewers were similar for all methods. Efficacy was higher in the PAL
      group (4 min x 100 cm3 fat aspirated) than in SAL (7 min x 100 cm3 fat) and UAL
      (10 min x 100 cm3 fat). Surgeon's distress was higher in PAL than in SAL and UAL.
      Surgeon's fatigue was much lower in the PAL group than in the others. Costs
      expressed as multiples of 1 unit (1 unit = $500 U.S.) were highest for UAL, low
      for PAL, and lowest for SAL. In conclusion, PAL and UAL caused reduced vascular
      injury, UAL being more selective for adipocyte removal. Complications of UAL and
      PAL were mostly related to the longer learning curve of these methods. The UAL
      procedure was much more expensive than PAL and, especially, SAL. PAL proved to be
      a handy technique, with the most favorable cost/benefit ratio, and seems to be
      the best option for busy liposuction practices or fast office procedures, even
      though the choice of the ideal technique always depends on the surgeon's
      preference.

PMID- 11246427
TI  - Contour surgery in the patient with great weight loss.
AB  - Obesity can be defined as a chronic disease in which there is excess of body
      adiposity, leading to severe secondary health problems. This metabolic pathology
      shortens life-span and is a main cause of diabetes, atherosclerosis, systemic
      arterial hypertension, and reduction of pulmonary function, among others. The
      plastic surgeon is involved with the obese patient under two circumstances:
      either the patient is currently overweight and requests reduction of excess
      adipose tissue, or has suffered a great weight loss and desires correction of
      one, or more, contour deformities. In either case, planning demands a close
      preoperative analysis and careful preparation of the patient, execution of a
      meticulous surgical routine, and close postoperative follow-up. In this article,
      various body contour deformities will be addressed, showing the senior author's
      strategy in treating the obese patient that has achieved the loss of considerable
      weight.

PMID- 11246426
TI  - Lipoplastics of legs: our experience with a new cannula compared with classical
      technique.
AB  - The Authors compare the results obtained between two groups of patients suffering
      from leg lipodystrophy, who were subjected to a reducing lipoplasty. In the first
      group, surgeons made use of a new sort of cannula, deprived of the classical
      grip, whereas in the second group, they employed the traditional probe. The best
      results, achieved with the first group, prove this new operating system is really
      effective, particularly on legs, for the following reasons: (1) Higher precision
      and better control of the instrument (2) Swan-neck cannula abolition (3)
      Opportunity to operate with both hands (4) Halved operating time (5) No tiredness
      after the operation.

PMID- 11246428
TI  - Gluteus augmentation with fat grafting.
AB  - This study presents the authors' experience with gluteus augmentation with
      autologus fat grafts and liposuction methods, having recorded the evolution of
      gluteus reshaping with autologus intramuscular fat graft injections for the past
      5 years. Preoperative shape is discussed and patient evaluations, operative
      techniques, postoperative management, and longterm results are emphasized.

PMID- 11246430
TI  - Benefits from lifting of the lower eyelid.
AB  - Lifting the lower eyelid includes removing skin excess of the lid and, most of
      the time, improves the fat herniation without any removal of the fat because of
      the tension of the orbicularis muscle obtained with this maneuver. The "lifting"
      also corrects the arcus marginalis as well as malar bags when they exist. Most of
      the crow's-feet lines are eliminated by this procedure, and the superior aspect
      of the nasolabial fold is often considerably smoothed.

PMID- 11246429
TI  - Orbital septorhaphy for the correction of baggy upper and lower eyelids.
AB  - Eyelid bags are the result of relaxation of lid structures like the skin, the
      orbicularis muscle, and mainly the septum, with subsequent protrusion or pseudo
      herniation of intraorbital fat contents. The logical treatment of baggy upper and
      lower eyelids should therefore include repositioning the herniated fat into the
      orbit and strengthening the attenuated septum in the form of a septorhaphy as a
      hernia repair. The preservation of orbital fat results in a more youthful
      appearance. The operative technique of the orbital septorhaphy is demonstrated
      for the upper and lower eyelid. A prospective series of 60 patients (50 upper and
      90 lower blepharoplasties) with a maximum follow-up of 17 months were analyzed.
      Pleasing results were achieved in 56 patients. A partial recurrence was noted in
      3 patients and widening of the palpebral fissure in 1 patient. Orbital
      septorhaphy for baggy eyelids is a rational, reliable procedure to correct the
      herniation of orbital fat in the upper and lower eyelids. Tightening of the
      orbicularis muscle and skin may be added as usual. The procedure is technically
      simple and without trauma to the orbital contents. The morbidity is minimal, the
      rate of complications is low, and the results are pleasing and reliable.

PMID- 11246431
TI  - Correction of sideburn defects after facelift operations.
AB  - The senior author has been using micrografts for correction of male pattern
      baldness since 1978. He has also been using these small grafts for correction of
      temporal hairline and loss of sideburn due to rhytidectomies, burns, avulsions,
      irradiation, and alopecia triangularis congenitas circumscripta [1,2]. Technique
      and results are presented.

PMID- 11246432
TI  - The "lazy S-shaped" plication of the SMAS-platysma musculoaponeurotic system: a
      10-year review.
AB  - Morphological changes that appear with the aging process are expressed by loss of
      the youthful face and neck contours. A "lazy S-shaped" plication involving the
      superficial musculoaponeurotic system (SMAS)-Platysma has been performed to
      recover the face and neck contour. On the neck, the posterior segment of the
      lateral portion of the muscle was stretched upward and backward to the mastoid.
      On the face, plication was done laterally and superiorly to the corner of the
      mouth toward the zygomatic arch. The anterior platysmal bands were approached in
      the midline to reinforce the muscle sling of the neck. Extensive skin dissection
      with suction lipectomy under direct visualization of the submental and cervical
      fat were associated. Photographs were taken preoperatively, 1 year, and 10 years
      after the surgery. Face and neck contour at 10 years was compared with that at 1
      year after the surgery and with the patient look before the surgery. Improvement
      of the face and neck contour was achieved in all patients at 1 year
      postoperatively. At 10 years after the surgery the face and neck contour was
      equal or eventually better than before the surgery.

PMID- 11246433
TI  - Augmentation mammaplasty with a new cohesive gel prosthesis.
AB  - We present our experience with augmentation mammaplasty on 14 patients with a
      thin chest wall and poor subcutaneous tissue. Thanks to Polytech Silimed code
      20675, a new anatomical prosthesis filled with "soft" cohesive gel, the lodging
      in a subglandular position was possible without anomalous salience in the upper
      pole, and a more natural mammary profile was achieved without capsular
      contracture, dislocation, or misplacement of the mammary implants.

PMID- 11246434
TI  - The tuberous breast syndrome.
AB  - The tuberous breast syndrome is the result of a complex series of defects with
      various degrees of expression. However, much confusion has been generated in the
      literature by the use of often inadequate terminology, which is partly the cause
      of multiplicity of managements being proposed that mainly aim to correct the
      major defect and not the entire syndrome. The surgical approach adopted by our
      group stems from the improvement of classic techniques, consisting essentially of
      a combination of periareolar mastopexis, additive mastoplasty, and gland base
      enlargement by cross incision. Our results were fully satisfying both
      aesthetically and functionally. We achieved a correct shape, resolved ptosys and
      reduced areolas with no double-fold effect, and attained good symmetry in more
      complex unilateral cases.

PMID- 11246435
TI  - Circumareolar mastectomy in female-to-male transsexuals and large gynecomastias:
      a personal approach.
AB  - Breast reduction or amputation in female-to-male surgery presents a specific
      surgical problem: obtaining a good breast shape of the masculine type. Over a 2
      year period, 17 patients (12 female-to-male transsexuals and 5 extreme
      gynecomastias) were operated on using the circumareolar approach for subcutaneous
      mastectomy. The nipple-areola complex was left on a very wide deepithelialized
      dermal pedicle, and the final closure of the wound was performed using a round
      block technique followed by numerous fine sutures to reduce wrinkling. This
      technique provides naturally flat masculine breasts, leaving sufficient dermal
      vascularization for the nipple-areola complex which is of the utmost importance.
      All the patients were very satisfied with the result because of the periareolar
      scar only. Two areolar necroses occurred due to perforation of the thin vascular
      dermal pedicle: one superficial which epithelialized spontaneously in a short
      period of time and one deeper which required skin grafting.

PMID- 11246436
TI  - Submuscular periareolar approach to augmentation mammoplasty in Korean women.
AB  - Augmentation mammoplasty can be approached by various methods according to the
      type of implant and implantation site depending on the status of the patient or
      surgeon's preference. The advantage for submuscular placement is based on
      problems associated with subglandular placement, especially capsular contracture
      and sensory changes in the nipple, and interference with the interpretation of
      mammograms is avoided. There are fewer complications such as hematoma, infection,
      and extrusion of the implant with submuscular dissection and relatively
      avascular, minimal sensory changes in the nipple compared with subglandular
      approach. The submuscular periareolar approach to augmentation mammoplasty was
      first described in the 1970s. This approach provides easy access to both the
      subglandular and subpectoral planes. It also provides a central point of access
      for creation of the implant pocket, which allows for easier and more accurate
      dissection in all diameters. The resultant periareolar scar is usually minimal
      with less injury to breast parenchyme and eventual biopsy or mastectomy incision
      to be performed through or around the areola. During the period of March 1999 to
      January 2000, 19 cases of who received submuscular periareolar augmentation
      mammoplasty under general anesthesia resulted in favorable scars with accurate
      access to pocket margin, easier dissection, and less bleeding compared with
      submuscular transaxillary augmentation mammoplasty. In our experience with the
      submuscular periareolar approach to breast augmentation it was highly versatile,
      safe, and less painful; postoperative hematoma incidence was greatly reduced and
      breast tissue injury was minimized.

PMID- 11246437
TI  - Scar wars.

PMID- 11246450
TI  - Molecular scanning for mutations in the melanocortin-4 receptor gene in
      obese/diabetic Japanese.
AB  - Decreased function of the melanocortin-4 receptor (MC4R) was reported to cause
      late-onset obesity and insulin resistance in rodents. Thus mutations in the MC4R
      gene drew strong attention as a possible cause of obesity and diabetes. We
      screened for mutations in the MC4R gene in extremely obese [body mass index (BMI)
      > or = 35 kg/m2] Japanese with diabetes by direct sequencing. A heterozygous
      mutation (V103I) was detected in one case (2.0 %), however the frequency was not
      significantly different from that in non-obese (BMI < or = 24 kg/m2) and non
      diabetic subjects (2.7 %). No other mutations were detected. These results
      suggest that mutations including V103I in the MC4R gene are not a major cause of
      obesity or diabetes in Japanese.

PMID- 11246451
TI  - Molecular instability of the mitochondrial haplogroup T sequences at nucleotide
      positions 16292 and 16296.
AB  - The mitochondrial haplogroup T, characterized by the nucleotide motif 16126C
      16294T in the hypervariable segment I (HVS I), is one of the most frequent among
      Europeans. It has been shown that this haplogroup includes the only well-resolved
      subgroup, T1, but that other HVS I sequences cannot be differentiated into
      subgroups due to possible homoplasies at nucleotide positions 16292, 16296 and
      16304, leading to the reticulations in the topology of phylogenetic networks. To
      study the problem of molecular instability at these positions, we have performed
      an analysis of 159 previously published West Eurasian HVS I sequences belonging
      to haplogroup T, together with 12 new HVS I sequences of Eastern Slavs. These 12
      sequences represent 16.9% of a total of 71 samples analysed and identified as
      haplogroup T mtDNAs by RFLP analysis in this study. A search for rare point
      mutations associated with different combinations of nucleotides 16292T, 16296T
      and 16304C within the haplogroup T sequences, and specific to certain populations
      or a group of closely related-by-descent populations, was performed. This
      analysis revealed 11 marker mutations, each of which was characteristic for a
      certain group of linguistically or geographically close individuals - the Adygei,
      Germans, Kazakhs and linguistic isolates of the Eastern Italian Alps. The
      occurrence of these rare population-specific polymorphisms in association with
      various combinations of mutations at positions 16292 and 16296 on the haplogroup
      T background provides evidence of molecular instability at these nucleotide
      positions. Molecular instability in the haplogroup T HVS I sequences is also
      suggested by multiple independent losses of the haplogroup T diagnostic
      nucleotide variants in different populations. The results of the present study
      suggest that identical haplogroup T HVS I sequence types might have arisen
      independently in different human populations.

PMID- 11246452
TI  - Analysis of lipoprotein lipase haplotypes reveals associations not apparent from
      analysis of the constituent loci.
AB  - Simultaneously analysing genotype effects at several closely-linked loci may be
      preferable to analysing them separately, but can be difficult, due to multiple
      genotype classes, small class sizes, and non-independence induced by associations
      among loci. Analysis of haplotype effects offers an alternative approach. We
      studied effects of haplotypes comprising 3 loci (5' to 3': PvuII, HindIII, and
      Ser 447 -Stop) in the lipoprotein lipase (LPL) gene on plasma lipid levels and
      LPL activity, in 807 Dutch males with coronary atherosclerosis. We analysed
      haplotype effects in individuals for whom haplotypes could either be determined
      unequivocally or inferred with high probability, using contrasts suggested by
      likely evolutionary relationships among the haplotypes. One haplotype was
      associated with significantly higher total cholesterol, while another was
      associated with significantly lower triglyceride levels. Though these two
      haplotypes had generally opposite effects on lipids, both were associated with
      significantly higher LPL activity. In genotype analyses, the HindIII (-) allele
      was associated with higher LPL activity; however, one haplotype bearing it had no
      significant effect on LPL activity. Haplotypes thus provided more information
      than genotypes alone would have. The two haplotypes with consistently different
      effects on lipid levels despite similar effects on LPL activity, provide further
      evidence that aspects of LPL biology, apart from its catalytic function in
      lipolysis, may mediate its effects on plasma lipids at least in coronary artery
      disease patients.

PMID- 11246453
TI  - Linking genotype to aorto-coronary atherosclerosis: a model using familial
      hypercholesterolemia and aorto-coronary calcification.
AB  - Most studies of the pathogenesis of coronary heart disease occur between gene
      variants and biochemical or physiological variables known to be atherogenic. In
      many situations, however, the gene products are not necessarily known. We studied
      17 families (n = 122) with mutations in the low density lipoprotein (LDL)
      receptor gene as a model in which to test formally for linkage directly between
      an atherogenic genotype and ischemic heart disease (IHD) or aorto-coronary
      calcified atherosclerosis. In each family one of three different mutations was
      found: the Trp66-Gly mutation, the Trp23-Stop mutation, or a ten kilobase
      deletion removing exons 3-6 of the LDL receptor gene. Genomic DNA was used to
      determine these mutations by either enzymatic cleavage assays or Southern
      blotting. Aorto-coronary calcification was significantly associated with age and
      plasma cholesterol. Sex, hypertension, BMI and smoking were not associated with
      aorto-coronary calcification. Nonparametric analysis indicated significant
      linkage of the LDL receptor gene locus to aortic (p < 0.00005) and to aorto
      coronary calcified atherosclerosis (p < 0.00001). Assuming a dominant mode of
      inheritance, significant linkage was detected for aortic (LOD = 3.89) and aorto
      coronary calcified atherosclerosis (LOD = 4.10). We suggest that the
      atherogenicity of variations in other genes could be assessed by a similar
      approach.

PMID- 11246454
TI  - Skewed secondary sex ratio in the offspring of carriers of the 214G > A mutation
      of the RS1 gene.
AB  - Carriers of X-linked juvenile retinoschisis (RS) were previously suggested to
      give birth to an excess of boys. We determined the carrier status for the 214G >
      A mutation of the RS1 gene in 202 females belonging to a large RS founder
      pedigree. The secondary sex ratio (SSR) in the offspring of 149 carriers was
      129.8 (z = 2.25), which differed significantly from that of the Finnish
      population (SSR 106) but not from that of 53 non-carrier females belonging to the
      same pedigree (SSR 116.7; z = 0.51). Since possible causes for the skewed SSR
      include factors affecting fertilisation, implantation and embryonic death, we
      searched for expression of RS1 in various placental and uterine cells and found
      that, in addition to the retina, RS1 is expressed in the uterus. We hypothesize
      that the RS1 protein has a role in implantation or embryonic survival.

PMID- 11246455
TI  - Hardy-Weinberg quality control.
AB  - An efficient test of deviation from Hardy-Weinberg frequencies with one degree of
      freedom was applied to 44 marker loci in a genome scan, and 7 loci had a
      significant excess of apparent homozygotes (chi2 (1) > 6) suggestive of typing
      error. In this example evidence for linkage did not increase when outliers were
      censored. Statistical quality control is an essential part of genotyping, and the
      effect of mistyping and map error should be considered in evaluating any genome
      scan.

PMID- 11246456
TI  - Familial association of disease and the structure of trivariate distributions.
AB  - In its usual form, the multifactorial model of disease transmission assumes that
      the liabilities to disease have a multivariate normal distribution. This paper
      studies how sensitive to this assumption are the quantitative results from the
      model. Accordingly, bounds are established for the probability of a child having
      a disease, given that both parents have it and taking the heritability of the
      disease to be known. Unfortunately, these bounds turn out to be wide. For
      example, a probability that is 0.38 under the trivariate normal model may be as
      low as 0.12 or as high as 0.78 under other trivariate models, even if attention
      is restricted to those of variables-in-common form. The broader statistical issue
      of the meaning of trivariate dependence, as distinct from bivariate dependence,
      is also discussed.

PMID- 11246457
TI  - Power of variance component linkage analysis to detect quantitative trait loci.
AB  - Expressions are derived for the sample size required to achieve a given power in
      variance component linkage analysis of a quantitative trait in unascertained
      samples. For simplicity an additive model, comprising effects due to a single
      QTL, residual additive genetic factors, and individual-specific random
      environmental variation, is considered. Equations are given relating sample size
      to trait heritability for sibpairs, sib trios, nuclear families having two and
      three sibs, and arbitrary relative pairs. The effects of nonzero residual
      additive genetic variance and parental information are discussed, and a scale
      relationship for sample sizes with sibships and nuclear families is derived. For
      larger sampling structures such as extended pedigrees the inheritance space is
      randomly sampled and the relevant equations are solved numerically. Comparative
      power curves are presented for sibships of size 2-4 and for an extended pedigree
      of 48 individuals. Simulation results for sibpairs confirm the validity of the
      theoretical results.

PMID- 11246458
TI  - Isolation, sequence, and chromosomal localisation of the human IkappaBR gene
      (NFKBIL2).
AB  - The inhibitors of NF-kappaB (IkappaBs) play an important role in the regulation
      of the NF-kappaB pathway. IkappaBR (for IkappaB-Related) is proposed to be a
      novel member of this family. We report the cloning and characterization of the
      region of the human gene encoding the previously reported mRNA. This region
      contains 13 exons, spread over 6550 bp of genomic sequence. The coding sequence
      is only weakly similar to other IkappaBs and the exons display a more complicated
      structure than has been found in other members of the IkappaB gene family.
      Moreover, the positions of intron-exon junctions are different from those found
      in other IkappaB genes, even within the otherwise conserved ankyrin-like repeat
      region, suggesting that the IkappaBR gene is not a member of this extended gene
      family. We report a revised mRNA and protein sequence for IkappaBR, which
      predicts that the protein is larger than originally described. We also report the
      chromosomal localisation of the human IkappaBR gene (approved gene symbol
      NFKBIL2) to 8q24.3 using PCR-based somatic cell hybrid panel analysis and
      fluorescence in situ hybridization (FISH) mapping.

PMID- 11246459
TI  - Four novel mutations in the tyrosine hydroxylase gene in patients with infantile
      parkinsonism.
AB  - Mutation detection in the tyrosine hydroxylase gene (TH) was performed in
      patients from two families. DNA sequencing revealed the presence of four novel
      missense mutations (exon 9 and 14 in family A, exon 8 and 9 in family B); the
      mutations were confirmed with restriction enzyme analysis, and did not occur in
      control alleles. Three mutations are in the catalytic domain of the enzyme and
      one may disturb tetramerization. At the moment, all patients are in the fourth
      decade of life. For more than 30 years they have been able to live a normal life
      with low-dose L-DOPA medication.

PMID- 11246461
TI  - A two-locus model for non-syndromic congenital dysplasia of the hip (CDH).
AB  - Complex segregation analysis was conducted in a sample of 171 pedigrees collected
      through probands affected by non-syndromic dysplasia of the hip (CDH) treated in
      Ferrara's CDH Centre in the period 1991-6. The analysis favoured a two-locus
      model, in which the accepted segregation model at the major locus was compatible
      with recessive transmission, with a gene frequency of the deleterious allele of
      around 0.20. For the other locus, among the Mendelian hypotheses tested, the
      recessive model turned out to be the most parsimonious. When ultrasonographic
      level was examined as an indication of severity, a significant improvement in the
      fit of the model was observed, giving clear evidence that information on the
      severity of CDH is important for a better definition of the hereditary
      transmission model.

PMID- 11246460
TI  - A genome-based study of consanguinity in three co-resident endogamous Pakistan
      communities.
AB  - In a study based on 173 individuals drawn from three endogamous, co-resident
      communities in the province of Punjab, the Awan, Khattar and Rajpoot, an analysis
      of 10 autosomal single tandem repeats on chromosomes 13 and 15 revealed
      distinctive genetic profiles in each community. A total of 99 different alleles
      were detected, with 28 alleles (28.3%) shared by all three communities. The mean
      private allele frequency was 7.7%. There was a reduction in heterozygosity and
      high average inbreeding effects (FIS and/or HS), particularly in the Awan,
      indicating genetic isolation and a high cumulative level of autozygosity.
      Genotyping with eight Y-chromosome STRs resulted in the construction of six
      haplotypes, one each for the Awan and the Khattar but four for the Rajpoot,
      suggesting marked variation in the patterns of male founder effects in the
      history of each community. The lower than expected levels of homozygosity
      observed at a number of loci may be indicative of cosegregation of the STRs with
      nearby early development genes subject to selection.

PMID- 11246462
TI  - Equivalence by descent: pedigree analysis with inbreeding and gametic phase
      disequilibrium.
AB  - In the presence of gametic phase disequilibrium and inbreeding, multiple locus
      genotype frequencies cannot be written solely in terms of identity by descent
      (IBD) probabilities. Following Cockerham & Weir (1973) we introduce the concept
      of 'equivalence by descent' (EBD), an extension of the concept of IBD to include
      non-allelic genes. Two genes are said to be EBD if they derive ultimately from
      the same founding gamete of a pedigree. Allelic genes that are EBD are also IBD.
      For two loci 11 EBD probabilities, the 'J-coefficients,' are required and for
      three loci 117 J-coefficients are required to write genotype probabilities. It is
      shown how the 117 J-coefficients for three loci can be reduced to a basic set of
      37. Computer programs, written in the algebraic programming language, MAPLE, are
      described which are capable of calculating the two- and three-locus J
      coefficients for any pedigree, subject only to size limitations. The MAPLE
      packages are available from the author upon request.

PMID- 11246463
TI  - Cloning and characterization of the TATA-less promoter from the human GFI1 proto
      oncogene.
AB  - The growth factor independent 1 (GFI1) gene encodes a zinc finger protein which
      acts as a transcriptional repressor and confers growth factor independence on
      tumor cells, as suggested by the study of its mouse ortholog, Gfi1. We previously
      isolated the human GFI1 gene but no information about the structure and location
      of the promotor of this gene has been reported. In this study we have cloned and
      characterized the human GFI1 promoter. The nucleotide sequence of the promoter
      region is GC-rich and does not contain a typical TATA or CAAT box. Several Sp1
      sites are present and computer predictions indicate that either of the two Sp1
      sites might serve as the sites for transcription initiation. Analysis of various
      lengths of the promoter region using the luciferase reporter assay identifies a
      functional promoter that is active in NIH3T3 cells. The strongest activity lies
      within a region 312-602 basepairs upstream from the translation start site.

PMID- 11246464
TI  - The FMR2 gene, FRAXE and non-specific X-linked mental retardation: clinical and
      molecular aspects.
AB  - FRAXE fragile site associated mental retardation remains unique among X-linked
      mental retardation phenotypes due to its very mild to borderline nature (50< IQ<
      85). It is the most prevalent form of non-specific X-linked mental retardation so
      far delineated, with an estimated incidence of at least 1/50-100,000 males, and
      with more than 50 families known worldwide. The FRAXE site is within, or
      immediately adjacent to, the 5' untranslated region of the FMR2 gene.
      Hyperexpansion of the FRAXE CCG repeat silences transcription of the gene. The
      structure of FMR2 has been characterized, but its function remains unknown. Gene
      localizations for numerous (> 75) large families with non-specific X-linked
      mental retardation (MRX) have been determined so far. Recently the molecular
      basis for some of them has been unravelled by identification of the responsible
      genes, which participate in complex common signalling pathways. This review
      summarises the new data on FRAXE associated mental retardation and the FMR2 gene
      in the light of the recent discoveries of new genes responsible for other forms
      of non-specific X-linked mental retardation.

PMID- 11246465
TI  - Human 18 kDa phosphotyrosine protein phosphatase (ACP1) polymorphism: studies of
      rare variants provide evidence that substitutions within or near alternatively
      spliced exons affect splicing result.
AB  - The mammalian low molecular weight phosphotyrosine protein phosphatase is
      expressed as two distinct isoforms. The human 'fast' and 'slow' isoforms differ
      only in the sequence of an internal segment of 34 residues, and the ACP1 gene
      contains two adjacent exons (E3F and E3S) which encode these segments. We have
      previously suggested that the fast and slow isoforms are generated by mutually
      exclusive pre-mRNA splicing of E3F and E3S. The common alleles ACP1*A, *B and *C
      express the fast and slow isoforms in different ratios. The *A and *C alleles
      differ from *B by C --> T transitions in E3S and E3F respectively. To test the
      idea that the fast : slow ratio is determined by nucleotide substitutions in the
      E3F-I3F-E3S region, four groups of rare ACP1 variants with unusual fast : slow
      ratios and the rare *E and *R alleles, expressing fast&ratio;slow ratios similar
      to *C and *B, respectively, were analysed. Gene segments of the I2-I3S region
      were amplified by PCR and analysed by SSCP and variant bands were excised and
      sequenced. For each of the rare isozymic variants one of six different nucleotide
      substitutions in E3F (nts+42, +85, +109, +110), I3F (nt+1) and I3S (nt+8) was
      observed. The *E and *R alleles showed C and B sequence, respectively, in
      accordance with the fast : slow ratio. The results support the hypothesis that
      the fast : slow ratio is constitutive.

PMID- 11246466
TI  - Microsatellite evolution in modern humans: a comparison of two data sets from the
      same populations.
AB  - We genotyped 64 dinucleotide microsatellite repeats in individuals from
      populations that represent all inhabited continents. Microsatellite summary
      statistics are reported for these data, as well as for a data set that includes
      28 out of 30 loci studied by Bowcock et al. (1994) in the same individuals. For
      both data sets, diversity statistics such as heterozygosity, number of alleles
      per locus, and number of private alleles per locus produced the highest values in
      Africans, intermediate values in Europeans and Asians, and low values in
      Americans. Evolutionary trees of populations based on genetic distances separated
      groups from different continents. Corresponding trees were topologically similar
      for the two data sets, with the exception that the (deltamu)2 genetic distance
      reliably distinguished groups from different continents for the larger data set,
      but not for the smaller one. Consistent with our results from diversity
      statistics and from evolutionary trees, population growth statistics S k and
      beta, which seem particularly useful for indicating recent and ancient population
      size changes, confirm a model of human evolution in which human populations
      expand in size and through space following the departure of a small group from
      Africa.

PMID- 11246467
TI  - Beta2-adrenergic receptor allele frequencies in the Quechua, a high altitude
      native population.
AB  - The beta2-adrenergic receptor is involved in the control of numerous
      physiological processes and, as the primary catecholamine receptor in the lungs,
      is of particular importance in the regulation of pulmonary function. There are
      several polymorphic loci in the beta2-adrenergic receptor gene that have alleles
      that alter receptor function, including two (A/G46, G/C79) that increase agonist
      sensitivity. As such a phenotype may increase vaso and bronchial dilation,
      thereby facilitating air and blood flow through the lungs, we hypothesized that
      selection may have favoured these alleles in high altitude populations as part of
      an adaptive strategy to deal with the hypoxic conditions characteristic of such
      environments. We tested this hypothesis by determining the allele frequencies for
      these two polymorphisms, as well one additional missense mutation (C/T491) and
      two silent mutations (G/A252 and C/A523) in 63 Quechua speaking natives from
      communities located between 3200 and 4200 m on the Peruvian altiplano. These
      frequencies were compared with those of two lowland populations, one native
      American (Na-Dene from the west coast of Canada) and one Caucasian of Western
      European descent. The Quechua manifest many of the pulmonary characteristics of
      high altitude populations and differences in allele frequencies between the
      Quechua and lowlanders could be indicative of a selective advantage conferred by
      certain genotypes in high altitude environments. Allele frequencies varied
      between populations at some loci and patterns of linkage disequilibrium differed
      between the old-world and new-world samples; however, as these populations are
      not closely related, significant variation would be expected due to stochastic
      effects alone. Neither of the alleles associated with increased receptor
      sensitivity (A46, G79) was significantly over-represented in the Quechua compared
      with either lowland group. The Quechua were monomorphic for the C allele at base
      79. This variant has been associated with body mass index; however no clearly
      defined metabolic phenotype has been established. In addition, we sequenced the
      coding region of the gene in three unrelated Quechua to determine if there were
      any other polymorphisms common in this population. None were detected.

PMID- 11246468
TI  - Probable ancestors of Hungarian ethnic groups: an admixture analysis.
AB  - The history of Hungary starts in the 9th century with the arrival of the Magyars
      in the Carpathian Basin. They spoke, like modern Hungarians, an Uralic language
      belonging to the Finno-Ugric language group. Their original composition probably
      included Iranian and Turkish people, while other populations were already present
      in the territory (Avars, Slavs, Germans). Some of the Hungarian ethnic groups
      claim to be descendants of ancient Magyars settlers (such as the Orseg), others
      of Huns, Turks or Iranians. We collected and compared the previously published
      gene frequencies of eight ethnic groups and seven hypothetical ancestral
      populations, including Uralics, applying a model of admixture. The results, most
      of which confirm historical hypotheses or the oral tradition, show that only one
      ethnic group (Orseg) highly resembles the Uralic population.

PMID- 11246469
TI  - The effect of marker characteristics on the power to detect linkage
      disequilibrium due to single or multiple ancestral mutations.
AB  - An important design issue in allelic association studies for mapping disease
      genes is the choice of markers. We have used a simple model of a founder
      population, similar to those of Ott & Rabinowitz (1997) and Chapman & Wijsman
      (1998), to explore the effect of the number of alleles at a marker polymorphism
      on the power to detect linkage disequilibrium due to single or multiple ancestral
      disease mutations. We show that the optimal number of alleles is more than 2 even
      in the case of a single ancestral disease mutation, and much higher still if
      multiple ancestral mutations are present. In large samples, much power is lost by
      using too few alleles, but relatively little power is lost by using too many
      alleles. These results confirm the desirability of using highly polymorphic
      markers or multi-locus haplotypes for association analysis. They also show that
      multiple ancestral disease mutations do not necessarily preclude linkage
      disequilibrium mapping, if highly polymorphic markers or multi-locus haplotypes
      are used.

PMID- 11246470
TI  - Estimation of admixture and detection of linkage in admixed populations by a
      Bayesian approach: application to African-American populations.
AB  - We describe a novel method for analysis of marker genotype data from admixed
      populations, based on a hybrid of Bayesian and frequentist approaches in which
      the posterior distribution is generated by Markov chain simulation and score
      tests are obtained from the missing-data likelihood. We analysed data on
      unrelated individuals from eight African-American populations, genotyped at ten
      marker loci of which two (FY and AT3) are linked (22 cM apart). Linkage between
      these two loci was detected by testing for association of ancestry conditional on
      parental admixture. The strength of this association was consistent with European
      gene flow into the African-American population between five and nine generations
      ago. To mimic the mapping of an unknown gene in an 'affecteds- only' analysis, a
      binary trait was constructed from the genotype at the AT3 locus and a score test
      was shown to detect linkage of this 'trait' with the FY locus. Mis-specification
      of the ancestry-specific allele frequencies - the probabilities of each allelic
      state given the ancestry of the allele - was detected at three of the ten marker
      loci. The methods described here have wide application to the analysis of data
      from admixed populations, allowing the effects of linkage and population
      structure (variation of admixture between individuals) to be distinguished. With
      more markers and a more complex statistical model, genes underlying ethnic
      differences in disease risk could be mapped by this approach.

PMID- 11246471
TI  - Association of a polymorphism at the 5'-region of the angiotensin II type 1
      receptor with hypertension.
AB  - Molecular variants of individual components of the renin-angiotensin system are
      thought to contribute to inherited predisposition towards essential hypertension.
      Using polymerase chain reaction-denaturing gradient gel electrophoresis (PCR
      DGGE) and sequence analysis, we identified seven polymorphisms in the 5'-flanking
      region of the angiotensin II type 1 receptor (AGTR1/AT 1 ) gene. We conducted a
      case-control study in a sample from the Japanese population to determine whether
      polymorphic markers in the 5'-flanking region of the AT 1 gene were associated
      with essential hypertension. The study compared 149 hypertensive subjects to 156
      normotensive control subjects. A significantly higher frequency of the AT 1 (
      535)*T allele was observed in hypertensive subjects. Evidence was obtained that
      the AT 1 (-535)*T allele showed a synergistic effect on risk of hypertension with
      angiotensin I converting enzyme D allele (ACE*D).

PMID- 11246472
TI  - Adaptation of the extended transmission/disequilibrium test to distinguish
      disease associations of multiple loci: the Conditional Extended
      Transmission/Disequilibrium Test.
AB  - Linkage and association studies in complex diseases are used to identify and fine
      map disease loci. The process of identifying the aetiological polymorphism, the
      molecular variant responsible for the linkage and association of the chromosome
      region with disease, is complicated by the low penetrance of the disease variant,
      the linkage disequilibrium between physically-linked polymorphic markers flanking
      the disease variant, and the possibility that more than one polymorphism in the
      most associated region is aetiological. It is important to be able to detect
      additional disease determinants in a region containing a cluster of genes, such
      as the major histocompatibility complex (MHC) region on chromosome 6p21. Some
      methods have been developed for detection of additional variants, such as the
      Haplotype Method, Marker Association Segregation Chi-squares (MASC) Method, and
      the Homozygous Parent Test. Here, the Extended Transmission/Disequilibrium Test
      is adapted to test for association conditional on a previously associated locus.
      This test is referred to as the Conditional Extended TDT (CETDT). We discuss the
      advantages of the CETDT compared to existing methods and, using simulated data,
      investigate the effect of polymorphism, inheritance, and linkage disequilibrium
      on the CETDT.

PMID- 11246473
TI  - Conditional ETDT analysis of the human leukocyte antigen region in type 1
      diabetes.
AB  - Several studies have indicated that additional genes in the major
      histocompatibility complex (MHC) region, other than the class II genes HLA-DQB1
      and -DRB1 (the IDDM1 locus), may contribute to susceptibility and resistance to
      type 1 diabetes. The relative magnitude of these non- DR/DQ effects is uncertain
      and their map location is unknown owing to the extraordinary linkage
      disequilibrium that extends over the 3.5 Mb of the MHC. The homozygous parent
      test has been proposed as a method for detection of additional risk factors
      conditional on HLA-DQB1 and -DRB1. However, this method is inefficient since it
      uses only parents homozygous for the primary disease locus, the DQB1-DRB1
      haplotype. To overcome this limitation, Conditional ETDT was used in the present
      report to test for association conditional on the DQB1-DRB1 haplotype, thereby
      allowing all parents to be included in the analysis. First, we confirm in UK and
      Sardinian type 1 diabetic families that allelic variation at HLA-DRB1 has a very
      significant effect on the association of DQB1 and vice versa. The Conditional
      ETDT was then applied to the HLA TNF (tumour necrosis factor) region and
      microsatellite marker D6S273 region, both of which have been reported to
      contribute to IDDM1 independent of the HLA-DQB1-DRB1 genes. We found no evidence
      for a major role for either of these two regions in IDDM1.

PMID- 11246474
TI  - Fine scale association mapping of disease loci using simplex families.
AB  - We present a new method for the fine scale mapping of disease loci based on
      samples of simplex families, each containing an affected child. The method is
      based on a generalisation of a single locus allele transmission model to multiple
      marker loci. The model is developed under the assumption of a single ancestral
      mutation and allows for the calculation of posterior probabilities that each
      allele at a particular marker was present on the founder chromosome. We
      illustrate the method using simulated family data for cystic fibrosis and
      Huntingtons disease, for which the locations of mutations in the disease genes
      are now known. For both diseases, our new method provides good estimates of the
      location of the mutations.

PMID- 11246475
TI  - Effects of age at onset on the power of the affected sib pair and
      transmission/disequilibrium tests.
AB  - Information on the age of a patient at disease onset, an important feature of
      complex diseases, is often collected in studies designed to map the disease
      genes. Penetrance-model-free methods, requiring no specification of penetrance
      functions, have been used extensively for detecting linkage and association
      between marker and disease loci. In this paper, we conduct an analytical study to
      examine the effects of incorporation of age at onset information on the power of
      two commonly used penetrance-model-free methods, the affected sib-pair (ASP) and
      transmission/disequilibrium tests (TDT). Assuming a Cox model with a major gene
      effect for the age at onset, we quantify analytically how age at onset affects
      the identity by descent (IBD) probabilities, the mean IBD values, and the
      expected numbers of alleles transmitted from heterozygous parents to affected
      children under various genetic models. We show that the power of the mean IBD
      test and the TDT can be greatly affected by the ages at onset of affected
      siblings or children used in the study. Generally, the most powerful test for
      ASPs is that based on affected sib pairs both having early disease onset and for
      TDT analyses is that based on trios with early-onset children. Naively combining
      affected sib pairs with different ages at onset or parent-children trios with
      different ages at onset of affected children can result in reduced power for
      detecting linkage or association. These results may be used to guide collection
      and analysis of sib pairs or families for diseases with variable age at onset.

PMID- 11246476
TI  - An EM algorithm for obtaining maximum likelihood estimates in the multi-phenotype
      variance components linkage model.
AB  - In recent years variance components models have been developed for localising
      genes that contribute to human quantitative variation. In typical applications
      one assumes a multivariate normal model for phenotypes and estimates model
      parameters by maximum likelihood. For the joint analysis of several correlated
      phenotypes, however, finding the maximum likelihood estimates for an appropriate
      multivariate normal model can be a difficult computational task due to complex
      constraints among the model parameters. We propose an algorithm for computing
      maximum likelihood estimates in a multi-phenotype variance components linkage
      model that readily accommodates these parameter constraints. Data simulated for
      Genetic Analysis Workshop 10 are used to demonstrate the potential increase in
      power to detect linkage that can be obtained if correlated phenotypes are
      analysed jointly rather than individually.

PMID- 11246479
TI  - Fifty years of evolution: essays in honour of John Maynard Smith.

PMID- 11246480
TI  - Acceptance and digestibility of some selected browse feeds with varying tannin
      content as supplements in sheep nutrition in west Africa.
AB  - In 1994 and 1995 leaves from 10 selected West African trees and shrubs with
      varying tannin content were tested to determine their suitability as an
      alternative and supplementary browse feed for West African dwarf sheep to improve
      productivity in small-scale holdings in Benin. Dry matter intake per kg metabolic
      body weight (DM g/kg W0.75) varied between the different browse feeds and between
      the different trials and ranged from zero (Leucaena leucocephala) up to 26.7 DM
      g/kg W0.75 (Margaritaria discoidea). The digestibility of the organic matter
      varied between 58.9% (L. leucocephala) and 68.2% (Mallotus oppositifolius).
      Agelaea obliqua showed the highest levels of total phenols (10.2%), tannin
      phenols (8.8%) and extractable condensed tannins (8.0%). Leaves from various
      browse feeds are a good and protein-rich supplementary fodder in addition to the
      grass Panicum maximum. However, feeding of A. obliqua and Cnestis ferruginea
      should be avoided due to toxic components.

PMID- 11246482
TI  - Proceedings of the 1st Australian Schizophrenia Prevention Conference 1999.

PMID- 11246481
TI  - [Indicators of quality for hospital antisepsis].
AB  - In any health care institution, the most important quality indicator for
      antisepsis is the existence of systems of reference of use, secondly the
      knowledge of those systems and then the compliance by the different classes of
      professionals. These refrentials must be regularly evaluated and updated
      according to general consensus.

PMID- 11246484
TI  - 3rd Basic Multidisciplinary Hemodialysis Access Course. September 13-14, 2000.
      Maastricht, The Netherlands. Abstracts.

PMID- 11246483
TI  - Addictions 2000. Proceedings of an international symposium. Hyannis,
      Massachusetts, USA. 22-24 September 2000.

PMID- 11246485
TI  - Never audit alone--the case for audit teams.
AB  - On-site audits, conducted by technical and quality assurance (QA) experts at the
      data-gathering location, are the core of an effective QA program. However,
      inadequate resources for such audits are the bane of a QA program and,
      frequently, the proposed solution is to send only one auditor to the study site.
      There are several reasons why audits should be performed by more than one person:
      1. SAFETY: Audits of EPA projects frequently involve hazardous chemicals or other
      environmental hazards. They also often involve working after normal work hours in
      remote locations with dangerous equipment. It is unsafe to work alone under such
      conditions. 2. Skills: Many of EPA's projects are multidisciplinary, involving
      multiple measurements systems, several environmental media, and complex automated
      data collection and analysis systems. It is unlikely that one auditor would have
      the requisite skills to assess all of these operations. 3. Separateness: Two
      auditors can provide two (sometimes differing) perspectives on problems
      encountered during an audit. Two auditors can provide complementary expertise and
      work experience. Two auditors can provide twice the surveillance power. 4.
      Support: The operations that need to be assessed are sometimes in different parts
      of a site, requiring two auditing devices or considerable commuting time. Also,
      auditors are occasionally diverted by managers wishing to show their best efforts
      rather than the whole operation; if two auditors are on-site, one can interview
      managers while the other talks with technical staff. If there is a dispute, one
      auditor can support the other in verifying observations. 5. Savings: Although
      sending one auditor is perceived to be a cost-saving measure, it may be more
      economical to send two auditors. Time on site (lodging, food) is decreased, more
      of the project is assessed in one visit, less pre-audit training is required, and
      report preparation is accelerated. In summary, sending more than one auditor on a
      field audit is smarter, safer and more effective, and can be less expensive in
      the long run.

PMID- 11246486
TI  - Validating existing data in the Environmental Technology Verification Program.
AB  - Establishing the credibility of existing data is an ongoing issue, particularly
      when the data sets are to be used for a secondary purpose, i.e., not the original
      reason for which they were collected. If the secondary purpose is similar to the
      primary purpose, the potential user may have little difficulty establishing
      credibility since the acceptance criteria for both purposes should be similar. If
      the secondary purpose is different, then data credibility may be more difficult
      to establish because the experiment generating the data may not have been
      conducted optimally for the secondary purpose and all of the necessary quality
      assurance data ("metadata") may not have been collected. In either case, a
      process will be required to determine the acceptability of the data. For this
      reason, at the time the U.S. Environmental Protection Agency (EPA) Environmental
      Technology Verification (ETV) program was established, similar certification and
      verification programs run by states or foreign countries routinely used existing
      data sets, for cost reasons, rather than generate new data by testing. The issue
      of whether existing data could be used in the ETV program immediately surfaced.
      In response, a policy and a process that addressed existing data were written and
      published in Appendix C of the ETV Quality and Management Plan (Hayes et al.,
      1998). This paper discusses how the ETV program determines the credibility of
      existing data used to verify the performance of environmental technologies.

PMID- 11246487
TI  - Association of particulate matter components with daily mortality and morbidity
      in urban populations.
AB  - Indices of atmospheric particulate matter (PM) have been reported to be
      associated with daily mortality and morbidity in a large number of recent time
      series studies. However, the question remains as to which components of PM are
      responsible for the reported associations. Multiple PM components rarely are
      measured simultaneously. To investigate PM effects on mortality and morbidity, we
      used the multiple PM components measured in Windsor, Ontario, at a site only a
      few miles from downtown Detroit, Michigan. This study focused primarily on two
      study periods in which multiple PM components were measured in Windsor: 1985 to
      1990, when levels of total suspended particles (TSP), sulfate from TSP (TSP-SO4(2
      )), PM less than 10 microns in diameter (PM10), and nonthoracic TSP (TSP-PM10)
      were measured throughout the year; and 1992 to 1994, when data on PM10, PM2.5 (PM
      less than 2.5 microns in diameter), PM10-2.5 (PM10 minus PM2.5), particle acidity
      (H+), and artifact-free sulfates (SO4(2-)) were available for mostly summer
      months. Mortality data were analyzed for the 1985 to 1990 study period, and data
      on both mortality and hospital admissions of elderly patients were analyzed for
      the 1992 through 1994 period. Poisson regressions were used to estimate the
      effects of these PM components and gaseous criteria pollutants on mortality
      (nonaccidental, circulatory, respiratory, and nonaccidental without circulatory
      and respiratory) and on hospital admissions of elderly patients (for pneumonia,
      chronic obstructive pulmonary disease [COPD], ischemic heart disease,
      dysrhythmias, heart failure, and stroke), adjusting for temperature and humidity,
      trends and seasonal cycles, and day of the week. Both PM10 and TSP were
      associated significantly with respiratory mortality for the 1985 to 1990 period,
      with similar relative risk (RR) estimates for PM10 (RR = 1.123; 95% confidence
      interval [CI] 1.0361-1.218) and TSP (RR = 1.109; 95% CI 1.028-1.197), per 5th to
      95th percentile increment. The effect-size estimates for TSP-SO4(2-) and TSP-PM10
      were smaller and less significant. In two-pollutant models, simultaneous
      inclusion of gaseous pollutants with PM10 or TSP reduced PM coefficients by 0 to
      34%. The effect-size estimates for total mortality, circulatory mortality, and
      total minus circulatory and respiratory mortality were less than those for
      respiratory mortality. Ozone (O3) and nitrogen dioxide (NO2) also were associated
      significantly with total and circulatory mortality, but a simultaneous
      consideration of these pollutants with PM10 reduced PM10 coefficients only
      slightly, or even increased them. In these results, pollution coefficients often
      were positive at multiple lag days (0-day through 3-day lags were examined), but
      for PM indices, 1-day lag coefficients were most significant. However, when all
      combinations of multiple-day average exposures were examined, for cases in which
      multiple lag days were positive, the choice of single-day or multiple-day average
      exposure did not appreciably change the estimated effect sizes. An examination of
      temporal correlation showed that the order of spatial uniformity as expressed by
      the median site-to-site correlation was O3 (0.83), PM10 (0.78), TSP (0.71), NO2
      (0.70), carbon monoxide (CO) (0.50), and sulfur dioxide (SO2) (0.49), which
      suggests less exposure error for O3 and PM10 than for the other measured
      pollutants. Thus, these results suggest that spatially homogeneous pollution
      indices show higher associations with measured health outcomes.

PMID- 11246488
TI  - Generation of oligodendroglial progenitors from neural stem cells.
AB  - To understand how the differentiation of stem cells to oligodendroglial
      progenitors is regulated, we established cultures of neural stem cells from
      neonatal rat striatum in the presence of epidermal growth factor (EGF) as free
      floating neurospheres that were then exposed to an increasing amount of B104 cell
      conditioned medium (B104CM). The resultant cells proliferated in response to
      B104CM but no longer to EGF. In vitro analysis and transplantation studies
      indicated that these cells were committed to the oligodendroglial lineage, and
      they were thus referred to as oligospheres. Further characterization of their
      expression of early markers, cell cycle, migration, and self-renewal suggests
      that they were pre-O2A progenitors. RT-PCR analysis indicated that the
      oligosphere cells expressed mRNAs of platelet-derived growth factor alpha
      receptor in addition to fibroblast growth factor receptor but not EGF receptor;
      the latter two receptor mRNAs were expressed by neurosphere cells. Thus, the
      progression of stem cells to oligodendroglial progenitors is likely induced by
      factors in B104CM.

PMID- 11246489
TI  - Suramin disrupts the gliotic response following a stab wound injury to the adult
      rat brain.
AB  - Reactive gliosis, observed in numerous pathological states, leads to the
      formation of a glial scar that is believed to impede axonal regeneration.
      Astrocyte reactivity can be initiated both in vitro and in vivo by various
      cytokines. Thus, the aim of this study was to investigate if suramin, a
      polysulfonated napthylurea that has been shown to inhibit the binding of many
      different cytokines to their cell surface receptors, could attenuate the glial
      response after brain injury. A single dose of suramin (5 microl, 75 microM) or
      saline vehicle was injected intracerebrally through the same needle used to make
      the stab wound at the time of lesioning. Suramin-treated animals showed an
      obvious reduction in several parameters of CNS inflammation: cellular
      proliferation, GFAP levels, and tenascin-C immunoreactivity were reduced in
      suramin-treated as compared to control animals at early time points. GFAP
      immunoreactivity was strikingly reduced at 3 days after injury, as confirmed by
      Western blot analysis. This reduction was transient, however, in that the
      difference in GFAP expression between suramin-treated and control animals was
      less apparent at 7 days and had disappeared by 30 days after injury. Likewise,
      fewer BrdU-positive cells were noted in treated versus control tissue at 1 and 3
      days, but this difference was not significant by 7 days. Moreover, tenascin
      immunoreactivity was significantly diminished at 24 h as confirmed by Western
      blot analysis in suramin-treated lesion areas, which is analogous to our
      observations that suramin can antagonize tenascin expression by cultured
      astrocytes treated with bFGF. In addition, examination of the corpus callosum of
      saline-treated animals 30 days post-trauma revealed a disruption of the fiber
      tract within the lesion site, while suramin-treated animals displayed numerous
      fibers spanning the lesion. These results demonstrate that a single injection of
      suramin transiently inhibits the gliotic response, which may be sufficient to
      ameliorate subsequent tissue damage.

PMID- 11246490
TI  - Laser scanning confocal microscopy of the hearing organ: fluorochrome-dependent
      cellular damage is seen after overexposure.
AB  - In order to combine laser confocal microscopy with physiological measurements, a
      number of conditions have to be met: the dye must not be toxic to the cells the
      laser light itself must not damage the cells; and the excitation of the
      fluorochrome during imaging must not generate products with toxic effects. We
      have investigated these conditions the hearing organ of the guinea pig. Two dyes
      were used, namely, calcein-AM, which is metabolized in vital cells to a
      fluorescent product in the cytoplasm, and a lipophilic membrane dye. The effect
      of the dyes on cell function was tested in the intact hearing organ, maintained
      in the isolated temporal bone, by measuring the electrophysiological potentials
      generated by the sensory cells in response to tone pulses. The loading of the
      cells with the dyes had no adverse effects. The effect of the laser beam was
      explored on isolated coils from the cochlea. In two preparations, the specimens
      viewed in the confocal system were fixed and processed for electron microscopy.
      Identified cells were followed before, during, and after laser exposure and could
      ultimately be examined at the ultrastructural level. Exposure to the laser beam
      did not cause damage in unstained cells, even at high intensities. In stained
      tissue, confocal microscopy could safely be performed at normal beam intensity
      without causing ultrastructural changes. At high intensities, about 100 times
      normal for 60 times as long, irradiation damage was seen that was selective in
      that the cells stained with the different dyes exhibited damage at the different
      sites corresponding to the subcellular location of the dyes. Cells stained with
      calcein showed lysis of mitochondria and loss of cytoplasmic matrix, whereas
      cells stained with the styryl membrane dye showed swelling of subsurface
      cisternae, contortion of the cell wall, and shrinkage. The styryl dyes, in
      particular, which selectively stain the sensory and neuronal cells in the organ
      of Corti, could be exploited for phototoxic use.

PMID- 11246491
TI  - Structure of outer hair cell stereocilia links in the chinchilla.
AB  - The structure of side, tip, and "attachment" links of chinchilla outer hair cell
      (OHC) stereocilia was studied by transmission and scanning electron microscopy
      using tannic acid and Cuprolinic blue histochemical procedures. Tannic acid,
      which interacts with many different types of proteins and glycoproteins
      irrespective of their electrical charge, showed strong reactivity for the central
      area of the side links and weak reactivity for the marginal area of these links
      adjacent to the stereocilia membrane. Tannic acid treatment revealed the tip
      links as thin strands, about 5 nm thick. Attachment links were poorly visualized
      after tannic acid treatment and appeared as sparse filamentous strands at tips of
      the tallest OHC stereocilia. Cuprolinic blue, at a high critical electrolyte
      concentration, reacted with strongly negative, primarily sulfated, carbohydrate
      residues of glycoconjugate macromolecules. In contrast to the tannic acid
      treatment, the central portions of the OHC stereocilia side links were unstained
      after Cuprolinic blue treatment; however, membrane-associated ends of these links
      were darkly stained. The tip links showed a similar appearance as after tannic
      acid treatment; however, Cuprolinic blue revealed an electron-dense substructure
      at both ends of its insertion into the stereocilia. Cuprolinic blue reactive
      structures were also observed as attachment links only at the tips of the OHC
      stereocilia of the tallest row in each bundle. These structures formed a crown
      like array around the tip of each stereocilium. Their primary function appears to
      be attachment of type B fibrils of the tectorial membrane to the tallest OHC
      stereocilia. Cuprolinic blue reactive structures of the side, tip, and attachment
      links appear to contain acidic, sulfated residues of proteoglycans or
      glycoproteins. These structures may function as connective elements between the
      stereocilia links and the hair cell cytoskeleton.

PMID- 11246492
TI  - The distribution of single P2x1-receptor clusters on smooth muscle cells in
      relation to nerve varicosities in the rat urinary bladder.
AB  - The distribution of purinergic (P2x1) receptors on smooth muscle cells in
      relation to autonomic nerve varicosities in the rat urinary bladder has been
      determined using immunofluorescence and confocal microscopy. P2x1 receptors were
      visualized using rabbit polyclonal antibodies against the extracellular domain of
      the P2x1 receptor, and varicosities were visualized using a mouse monoclonal
      antibody against the ubiquitous synaptic vesicle proteoglycan SV2. Two size
      classes of P2x1 receptor clusters were observed on the smooth muscle cells of the
      detrusor, namely, a large ellipse of mean long axis 1.23+/-0.21 microm and short
      axis 0.92+/-0.17 microm and a smaller spherical cluster with a mean diameter of
      0.40+/-0.04 microm. The latter occured in much greater numbers than the former in
      selected areas, with a density as high as 0.8 per microm2 or two orders of
      magnitude more than the larger-sized clusters. The large clusters are in general
      located beneath varicosities, with only 4.5% of P2x1 clusters not possessing an
      overlying varicosity. None of the small clusters was associated with
      varicosities. Three-dimensional reconstruction of the P2x1 and SV2 labelling at
      individual varicosities showed that the varicosities were immediately apposed to
      the P2x1 receptor clusters. On occasions, two or more small SV2-labelled
      varicosities about 0.7 microm in diameter each with a receptor patch were found
      juxtaposed to each other; these might represent the splitting up of a single
      large varicosity. These observations are discussed in relation to the identity of
      the autonomic neuromuscular junction.

PMID- 11246493
TI  - The demonstration by transplantation of the very restricted remyelinating
      potential of post-mitotic oligodendrocytes.
AB  - To examine the remyelinating ability of post-mitotic oligodendrocytes, we
      subjected cell preparations derived from neonatal and adult rats to 40 Grays of X
      irradiation to remove mitotically active cells and injected them into areas of
      demyelination in which the inherent ability to generate remyelinating cells had
      been inhibited. The extensive remyelination seen following implantation of non
      irradiated neonatal and adult cells was almost completely abolished when the
      transplanted cell suspension was exposed to 40 Grays of X-irradiation,
      demonstrating that effective remyelination requires the generation of cells by
      mitosis. Radiation-resistant and therefore non-dividing oligodendrocytes were
      detected in areas of demyelination following transplantation of neonatal cultures
      and oligodendrocyte preparations derived from the adult nervous system. However,
      the pattern of myelin formation associated with the radiation-resistant
      oligodendrocytes from the two sources was different. Following implantation of X
      irradiated neonatal cultures, a small number of oligodendrocytes could be found
      within the area of demyelination, and although these cells formed sheets of
      myelin membrane, they did not form myelin sheaths. After implantation of X
      irradiated adult cells, in addition to the aberrant myelin formation seen with
      the neonatal cells, some myelin sheaths were observed. Our findings confirm that
      effective remyelination requires cell division and suggest that there may be
      diverse populations of radiation-resistant oligodendrocytes in the adult nervous
      system, some of which can form myelin sheaths and others of which can only make
      myelin sheets. Important for the interpretation of our previous studies is the
      demonstration here that 40 Grays of X-irradiation per se does not inhibit
      oligodendrocytes from remyelinating axons.

PMID- 11246494
TI  - Comparative study of acetylcholinesterase and butyrylcholinesterase in brain and
      serum of several freshwater fish: specific activities and in vitro inhibition by
      DDVP, an organophosphorus pesticide.
AB  - A comparative study of specific activities and in vitro inhibition of brain and
      serum acetylcholinesterase (AChE; EC 3.1.1.7) and serum butyrylcholinesterase
      (BChE; EC 3.1.1.8) by DDVP, an organophosphorus pesticide, was conducted in 11
      freshwater teleost species belonging to four families (Cyprinidae; common carp
      Cyprinus carpio, bream Abramis brama, blue bream A. ballerus, white bream Blicca
      bjoerkna, roach Rutilus rutilus, bleak Alburnus alburnus, ide Leuciscus idus;
      Percidae: perch Perca fluviatilis, pikeperch Stizostedion lucioperca; Esocidae:
      pike Esox lucius and Coregonidae: whitefish Coregonus albula). Specific AChE and
      BChE activities in brain and serum of fish were determined. Brain AChE activity
      varied among fish species approximately 10-fold, ranging from 192.6 to 1353.2
      micromol g(-1) h(-1), respectively in perch and whitefish. All cyprinids had
      higher brain AChE activity than those of other fish families. Serum AChE activity
      was 100-fold lower than in brain. Serum BChE activity was found only in cyprinids
      with the exception of the common carp. It varied from 163.8 to 970.3 micromol g(
      1) h(-1), respectively in roach and bleak. The bimolecular enzyme inhibition rate
      constants (kIIs) and pI50) values for DDVP were calculated. Sensitivity of fish
      AChEs both in brain and serum is similar to those of typical AChEs in mammals.
      The range of kIIs was 3.4-51.7 x 10(3) mol(-1) 1 min(-1) (pI50s were 5.3-6.5),
      respectively in white bream and ide. In contrast, fish serum BChE was more
      sensitive to inhibition than typical BChE and AChE in mammals. Values of kII for
      BChE were 1.0-2.5 x 10(7) mol(-1) 1 min(-1) (pI50 was 8.8-9.2), respectively in
      ide and bleak.

PMID- 11246496
TI  - In vivo metallothionein and glutathione status in an acute response to cadmium in
      Mercenaria mercenaria brown cells.
AB  - Brown cells that are found in the red glands of Mercenaria mercenaria accumulate,
      detoxify and excrete cadmium. Brown cell involvement in metal detoxification was
      due in part to endogenous glutathione (GSH) and protein sulfhydryl.
      Metallothionein (MT) and GSH have been shown to play an important role in metal
      detoxification in bivalve molluscs. This study showed that the protein sulfhydryl
      in brown cells of Mercenaria was in fact MT, that brown cell GSH functioned in
      acute protection against Cd2+ toxicity, that GSH provided the initial defense
      against Cd2+ toxicity prior to MT induction and that MT variants were unequal in
      response to Cd2+. During treatment of Mercenaria with 0.5 and 1.0 ppm Cd2+, brown
      cells were analyzed for MT by capillary electrophoresis and GSH colorimetrically
      after 0.25, 1, 2, 3, and 4 days. The data indicated that the cadmium-binding
      protein was MT with an apparent molecular weight of 9 kDa determined by gel
      filtration or 6 kDa as indicated by capillary electrophoresis. Glutathione
      appeared to prevail in the brown cell acute response to 0.5 ppm Cd2+, whereas MT
      appeared to prevail in the acute response to 1.0 ppm Cd2+. Capillary
      electrophoresis can be used to monitor and quantify MT and its variants in brown
      cells without need for prior separation of cytosolic components by
      chromatography. The change in MT-II was greater relative to the change in MT-I in
      the brown cell acute response to 0.5 ppm Cd2+, whereas the change in MT-1 was
      greater relative to the change in MT-II in the acute response to 1.0 ppm Cd2+.
      The variants of brown cell MT appeared to respond differentially to Cd2+
      depending upon the Cd2+ treatment concentration.

PMID- 11246495
TI  - Nitric oxide and inducible nitric oxide synthase expression are downregulated in
      acute cholestasis in the rat accompanied by liver ischemia.
AB  - Hepatic blood flow decreases under cholestasis and there is evidence that NO
      regulates liver microvascular perfusion. Thus, the aim of the present study was
      to evaluate NO synthesis in cholestasis. Cholestasis was induced by bile-duct
      ligation (BDL) in male Wistar rats. Bilirubins and enzyme activities were
      measured in serum. Lipid peroxidation, GSH, GSSG and glycogen were determined in
      liver. Histopathological analysis was performed. Serum NO2- + NO3- concentration
      was measured by the Gries reaction. iNOS immunoblot analysis was carried out
      using an iNOS polyclonal antibody. After 7 days of BDL lipid peroxidation
      increased while GSH/GSSG ratio decreased. Serum NO2- + NO3- and liver iNOS
      protein were reduced, accompanied by ischemia as revealed by the
      histopathological analysis. GSH upregulates NO synthesis by increasing iNOS mRNA
      levels and iNOS activity, thus the reduction of GSH/GSSG ratio may be responsible
      for the downregulation of iNOS protein and NO synthesis, which in turn may
      explain the observed ischemia and the decreased hepatic blood perfusion in
      cholestasis reported by others.

PMID- 11246497
TI  - Progesterone metabolism in the ovaries and testes of the echinoid Lytechinus
      variegatus Lamarck (Echinodermata).
AB  - In the present study we examined the metabolic fate of progesterone (P4) in
      homogenate and tissue minces of the ovaries and testes of Lytechinus variegatus.
      P4 was metabolized primarily into 5alpha-reduced metabolites including, 5alpha
      pregnane-3,20-dione (DHP), 3beta-hydroxy-5alpha-pregnan-20-one (3beta,20-one),
      5alpha-pregnane-3beta,20alpha-diol (3beta,20alpha-diol), 5alpha-pregnane
      3beta,20beta-diol (3beta,20beta-diol), and 5alpha-pregnane-3alpha,20alpha-diol
      (3alpha,20alpha-diol) by both the ovaries and testes. The capacity to metabolize
      P4 did not differ between the ovaries and testes. However, the relative quantity
      of Salpha-pregnane-3beta,20zeta-diol synthesized from ovary and testis tissue
      minces was about 3.3-fold higher than from homogenate preparations. Differences
      in the synthesis of 3beta,20-one and 3alpha,20alpha-diol in both ovary and testis
      minces were dependent on reproductive state. This study demonstrates the pathway
      of P4 conversion in the ovaries and testes of L. variegatus and indicates the
      rapid conversion of P4 into 5alpha-reduced metabolites in these tissues. Although
      P4 metabolism is not sex specific, sex-specific responses to P4 metabolites have
      been demonstrated previously. We hypothesize that the sex-specific responses of
      the ovaries and the testes to P4 may be associated with receptor-level regulatory
      processes.

PMID- 11246498
TI  - Activation and desensitization of the caffeine-sensitive cation channels and
      calcium stores have no persistent effect on the electrophysiological properties
      of leech P neurones.
AB  - In leech P neurones caffeine activates unselective ion channels in the plasma
      membrane and induces intracellular Ca2+ release (Schoppe, J., Hochstrate, P.,
      Schlue, W.-R., 1997. Caffeine mediates cation influx and intracellular Ca2+
      release in leech P neurones. Cell Calcium 22, 385-397). These effects are
      prominent only upon the first caffeine exposure, while subsequent applications
      are largely ineffective; i.e. both plasma membrane channels and intracellular
      Ca2+ release mechanism desensitize irreversibly. In order to examine whether this
      desensitization is paralleled by irreversible changes in the electrophysiological
      parameters of the cells, we investigated the action of caffeine on changes in
      membrane potential and the cytosolic free Ca2+ concentration, which were induced
      by varying the ionic composition of the extracellular fluid or by application of
      5-hydroxytryptamine. Neither the resting values nor any of the experimentally
      induced shifts in membrane potential or cytosolic Ca2+ concentration were
      affected by caffeine, which suggests strongly that activation and/or
      desensitization of the caffeine-sensitive ion channels and Ca2+ stores have no
      long-lasting effect on the relevant electrochemical gradients, membrane
      conductances, or transport mechanisms.

PMID- 11246499
TI  - In vivo changes in free choline level induced by autonomic agonists in mouse
      organs, including three major salivary glands.
AB  - Whether free choline levels are changeable in vivo in response to different types
      of autonomic agonists was examined in several mouse organs. Upon one subcutaneous
      injection of isoproterenol, phenylephrine and pilocarpine, choline levels in
      whole organ decreased, increased and decreased, respectively, in various organs
      within 30 min and returned to initial levels in a day. In the three major
      salivary glands, a delayed choline elevation also appeared on day 2 after one
      isoproterenol injection and subsided by day 6. Only in the three salivary glands
      more choline was accumulated after 10 once-a-day injections of isoproterenol than
      after one isoproterenol injection. Neither phenylephrine nor pilocarpine induced
      comparable choline accumulation in any organs examined. Isoproterenol injection
      repeated at a 2-day interval augmented the subsequent, delayed choline elevation.
      Examination with dobutamine and the adenylyl cyclase activator 6-(3
      dimethylaminopropionyl)forskolin suggested that isoproterenol-induced immediate
      choline lowering was down-stream of cAMP synthesis and linked to cAMP more
      tightly than the choline accumulation, though both choline changes occurred via
      beta1-adrenergic receptors. Choline levels in the salivary glands also changed
      depending on the form of diet given and particularly in the parotid gland in
      parallel with gland weights. These results provide the first evidence for the
      autonomic control of intracellular choline levels; intracellular choline levels
      might be an integral part of the autonomic signalling pathway.

PMID- 11246500
TI  - Combined effects of 2,4-D and azinphosmethyl on antioxidant enzymes and lipid
      peroxidation in liver of Oreochromis niloticus.
AB  - This study aims to investigate the effects of the herbicide 2,4-D and the
      insecticide azinphosmethyl on hepatic antioxidant enzyme activities and lipid
      peroxidation in tilapia. Fish were exposed to 27 ppm 2,4-D, 0.03 ppm
      azinphosmethyl and to a mixture of both for 24, 48, 72 and 96 h. Activities of
      catalase (EC 1.11.1.6), glutathione-S-transferase (GST, EC 2.5.1.18) and the
      level of malondialdehyde (MDA) in the liver of Oreochromis niloticus exposed to
      2,4-D and azinphosmethyl, both individually and in combination, were not affected
      by the pesticide exposures. However, glucose-6-phosphate dehydrogenase (G6PD, EC
      1.1.1.49) and glutathione reductase (GR, EC 1.6.4.2) activities in individual and
      combined treatments, increased significantly compared to controls. Furthermore,
      glutathione peroxidase (GPx, EC 1.11.1.9) activity increased in individual
      treatment, while the same enzyme activity decreased in combination. 2,4-D did not
      affect the activity of superoxide dismutase (SOD, EC 1.15.1.1), but the activity
      of this enzyme in azinphosmethyl treatment decreased, while its activity
      increased in combination. Combined treatment of the pesticides exerted
      synergistic effects in the activity of SOD, while antagonistic effects were found
      in the activities of G6PD, GPx, GR. The results indicate that O. niloticus
      resisted oxidative stress by antioxidant mechanisms and prevented increases in
      lipid peroxidation.

PMID- 11246501
TI  - Excitatory actions of propofol and ketamine in the snail Lymnaea stagnalis.
AB  - This study compares the actions of the intravenous anaesthetics propofol and
      ketamine on animal behaviour and neuronal activity in the snail Lymnaea
      stagnalis, particularly in relation to excitatory effects observed clinically.
      When injected into the whole animal, neither agent induced total anaesthesia.
      Rather, behavioural activity was enhanced by propofol (10(-5) M) and ketamine
      (10(-7) M), indicating excitatory effects. When superfused over the isolated
      central nervous system (CNS), differential effects were produced in two
      identified neurons, right pedal dorsal 1 (RPeD1) and visceral dorsal 4 (VD4).
      Resting membrane properties were largely unaffected. However, spike after
      hyperpolarisation was significantly reduced in RPeD1, but not VD4, with some
      evidence of increased excitability. In addition, an intrinsic bursting property
      (post-stimulus burst) in VD4 was altered by propofol (10(-7) M). The results
      suggest significant excitatory components in the actions of some intravenous
      anaesthetics, as well as a potential role in modifying excitation and bursting
      mechanisms in the CNS.

PMID- 11246502
TI  - Glutathione S-transferase and UDP-glucuronyltransferase activity in primary
      cultures of rainbow trout gill epithelial cells.
AB  - The objective of this study was to characterize rainbow trout (Oncorhynchus
      mykiss) gill epithelial cells in primary culture by evaluating their ability to
      maintain glutathione and glucuronide conjugating enzymes. The activity and
      inducibility of the phase II enzymes was investigated as a function of culture
      time. Glutathione S-transferase (GST) and UDP-glucuronyltransferase (UDPGT)
      enzyme activities were measured in freshly isolated cells and in cells cultured
      for 7 and 12 days. GST activity, determined with 1-chloro-2,4-dinitrobenzene,
      decreased gradually to 72% after 7 days and to 38% after 12 days in culture
      compared with freshly isolated cells. There was no significant difference between
      UDPGT activities in freshly isolated cells compared with cells cultured up to 12
      days although a transient decrease in activity was observed at day 7. In vitro
      induction of the enzymes was studied using beta-naphtoflavone (BNF) and 3
      methylcholanthrene (3-MC) as inducers. GST activity increased 2-fold after
      exposure to BNF and 1.5-fold after 3-MC exposure for 48 h in 7 days old cultures.
      No induction was observed in 12 days old cultures. UDPGT activity was not induced
      either at day 7 or 12.

PMID- 11246503
TI  - Growth, lipid class and fatty acid composition in juvenile mud crabs
      (Rhithropanopeus harrisii ) following larval exposure to Fenoxycarb, insect
      juvenile hormone analog.
AB  - This study examines the effects of Fenoxycarb on larval growth, and lipid class
      and fatty acid composition in first crabs of the mud crab Rhithropanopeus
      harrisii reared through total larval development in nominal water concentrations
      from 1 to 100 microg/l. In first crabs of R. harrisii, dry weight (microg)
      decreased significantly (P < 0.05) from 228.8+/-38.2 microg (n = 9) in the
      controls to 131.8+/-10.1 microg (n = 4) in animals exposed throughout larval
      development to 100 microg/l. A significant (P < 0.05) reduction was found between
      total lipid content in the controls and first crabs reared at concentrations
      greater than 50 microg/l. In relative terms (% dry weight), different lipid
      classes predominated in the controls and the various fenoxycarb exposure
      concentrations. There were no significant (P > 0.05) differences among the
      treatment groups in phospholipid level, while the triglyceride content was
      significantly lower in crabs exposed to 10 and 100 microg/l. No significant
      differences in the percent of free fatty acids were found in crabs exposed to 1
      10 microg/l and the controls. Free sterols in crabs exposed to concentrations
      higher than 10 microg/l were below the detection limit. Control animal fatty acid
      profiles were dominated by palmitic, stearic, and oleic acid, accounting for 48%
      of total fatty acids (TFA). The fatty acid composition of crabs exposed to 100
      microg/l significantly (P < 0.05) differed from the controls. The results suggest
      that fenoxycarb has substantial effects on growth, lipid class and fatty acid
      composition in developing larvae of R. harrisii at water concentrations greater
      than 10 microg/l.

PMID- 11246504
TI  - Cytochrome P450 4A, peroxisomal enzymes and nicotinamide cofactors in koala
      liver.
AB  - We have examined hepatic levels of microsomal lauric acid hydroxylase activity
      and cyanide-insensitive palmitoyl coenzyme A oxidative activity in koala
      (Phascolarctos cinereus) and tammar wallaby (Macropus eugenii) and compared our
      results to those determined in rat. Microsomal lauric acid hydroxylation was
      significantly higher in koala than in tammar wallaby or rat. However, cyanide
      insensitive palmitoyl-CoA oxidation was absent in the koala. We have also
      determined the hepatic nicotinamide cofactors in these species. Hepatic
      nicotinamide-adenine dinucleotide (NAD) and the ratio of NAD/nicotinamide-adenine
      dinucleotide phosphate (NADP) were higher in koala than in tammar wallaby and rat
      liver. Reverse transcription of koala liver mRNA, followed by polymerase chain
      reaction using primers based on highly conserved areas in the CYP4A family led to
      the cloning of a partial, near full length, cDNA clone with approximately 70%
      nucleotide and deduced amino acid sequence identity to human CYP4A11. The CYP has
      been named CYP4A15.

PMID- 11246505
TI  - Effects of zinc on lipids of erythrocytes from carp (Cyprinus carpio L.)
      acclimated to different temperatures.
AB  - We compared the effect of zinc (0.01, 0.1, 0.5 and 1 mM) at two temperatures (5
      and 20 degrees C) on erythrocytes from summer and winter acclimatised carp. An
      increase in temperature from 5 to 20 degrees C increased the unsaturation index
      (UI) and relative proportion (UI/SFA) of unsaturated to saturated fatty acids in
      total lipids of the red cells. At 5 degrees C, the unsaturation index of
      phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylethanolamine (PE)
      and phosphatidylinositol (PI) decreased (30-40%) in the presence of 1 mM zinc.
      The change in unsaturation of phospholipids in the presence of zinc at 5 degrees
      C is probably responsible for the alteration in structural integrity of
      erythrocyte membrane as observed by hemolysis and the decreased thiol group
      content in the erythrocytes. In light of this result, zinc may be considered an
      environmental hazard for these fish at low temperatures.

PMID- 11246506
TI  - Differential accessibility of bilirubin to erythrocyte membrane vesicles bearing
      different structural features.
AB  - Interaction of bilirubin with different types of erythrocyte membrane vesicles
      such as unsealed, heterogeneous, sealed and inside-out membrane vesicles prepared
      from human and goat erythrocytes was studied. Out of various types of membrane
      vesicles, in both species, unsealed membrane vesicles bound quantitatively higher
      amounts of bilirubin followed by heterogeneous and sealed membrane vesicles
      whereas inside-out membrane vesicles bound the lowest amount of bilirubin. These
      differences in the amount of bound bilirubin to different membrane vesicles were
      correlated well with the percentage accessibility of sialic acid to neuraminidase
      in these membranes suggesting that bilirubin bound preferentially to the outer
      layer of erythrocyte membranes than the inner layer. Further, membrane vesicles
      prepared from human erythrocytes bound higher amounts of bilirubin than those
      prepared from goat erythrocytes. This can be ascribed to different phospholipid
      composition of these membranes.

PMID- 11246507
TI  - Characterisation of tolbutamide hydroxylase activity in the common brushtail
      possum, (Trichosurus vulpecula) and koala (Phascolarctos cinereus): inhibition by
      the eucalyptus terpene 1,8-cineole.
AB  - Plant constituents such as terpenes are major constituents of the essential oil
      in Eucalyptus sp. 1,8-Cineole and p-cymene (Terpenes present in high amounts in
      Eucalyptus leaves) are potential substrates for the CYP family of enzymes. We
      have investigated tolbutamide hydroxylase as a probe substrate reaction in both
      koala and terpene pretreated and control brushtail possum liver microsomes and
      examined inhibition of this reaction by Eucalyptus terpenes. The specific
      activity determined for tolbutamide hydroxylase in the terpene treated brushtails
      was significantly higher than that for the control animals (1865+/-334 nmol/mg
      microsomal protein per min versus 895+/-27 nmol/mg microsomal protein per min).
      The activity determined in koala microsomes was 8159+/-370 nmol/mg microsomal
      protein per min. Vmax values and Km values for the terpene treated possum,
      control, possum and koala were 1932-2225 nmol/mg microsomal protein per min and
      0.80 0.81 mM; 1406-1484 nmol/mg microsomal protein per min and 0.87-0.92 mM and
      5895-6403 nmol/mg microsomal protein per min and 0.067-0.071 mM, respectively.
      Terpenes were examined as potential inhibitors of tolbutamide hydroxylase
      activity. 1,8-Cineole was found to be a competitive inhibitor for the enzyme
      responsible for tolbutamide hydroxylation (Ki 15 microM) in the possum. In koala
      liver microsomes stimulation of tolbutamide hydroxylase activity was observed
      when concentrations of cineole were increased. Therefore, although inhibition was
      observed, the type of inhibition could not be determined.

PMID- 11246508
TI  - Anxiolytic and anticonvulsant properties of doramectin in rats: behavioral and
      neurochemistric evaluations.
AB  - Doramecin is an antiparasitic drug that may interfere with gamma-aminobutyric
      acid (GABA) neurotransmission. Some behavioral manifestations are related with
      GABAergic neurotransmissions as anxiety and seizures. The objective of the
      present study was to examine the possible central nervous system (CNS) effects of
      doramectin (100, 300 and 1000 microg/kg, SC) in rats, using anxiety behavioral
      models, susceptibility to seizures and central neurotransmitter evaluations. The
      open-field results showed (i) few alterations in locomotion frequency; (ii) a
      biphasic effect on rearing frequency that may be the consequence of least
      habituation in open-field; (iii) the reduction of grooming durations might be
      attributed to a possible anxiolytic effect of doramectin since GABAergic agonists
      reduced this parameter in apparatus. Our data in the hole board showed no effects
      in locomotion and rearing frequencies but increased head dipping frequency of
      rats administered doramectin similarly to anxiolytic drugs. In plus-maze test,
      doramectin administration increased the number of entries and time into open
      arms, indicating also an anxiolytic effect. Doramectin protected animals from
      convulsant effects of picrotoxin, indicative of an anxiolytic pharmacological
      profile of a drug with GABAergic properties. The alterations observed in central
      dopaminergic, noradrenergic and serotoninergic neurotransmissions might be the
      consequence of reinforcement in central GABAergic neurotransmission induced by
      doramectin. The present results suggest that doramectin has the pharmacological
      profile of an anxiolytic/anticonvulsant drug with GABAergic properties.

PMID- 11246510
TI  - Organization of intestinal pacemakers.

PMID- 11246509
TI  - Thyroid hormone deiodination in tissues of American plaice, Hippoglossoides
      platessoides: characterization and short-term responses to polychlorinated
      biphenyls (PCBs) 77 and 126.
AB  - We have described the tissue distribution and properties of thyroid hormone (TH)
      deiodination activities of the marine American plaice, Hippoglossoides
      platessoides. We then studied the 1- or 4-week responses of the plaice liver and
      brain deiodination activities and the plasma thyroxine (T4) and 3,5,3'
      triiodothyronine (T3) levels to an intraperitoneal injection (5-500 ng/g) of the
      polychlorinated biphenyl (PCB) congeners 77 (3,3'-4,4'-tetrachlorobiphenyl) or
      126 (3,3',4,4',5-pentachlorobiphenyl). T4 and 3,3'5'-triiodothyronine (rT3) outer
      ring deiodination (ORD) activities were greater in liver than in kidney, gill,
      heart, brain, intestine or muscle; inner-ring deiodination (IRD) activity
      occurred in all tissues but was consistently higher in brain. Deiodination
      characteristics (optimal pH, optimal dithiothreitol concentration, responses to
      inhibitors and apparent Km values of 0.6-4 nM) fell in the same rage as those of
      low-Km deiodinases in other teleosts. Deiodination activities were maximal when
      assayed at 25 degrees C but uniformly low over the natural range of 0-9 degrees
      C. Neither PCB 77 nor PCB 126 altered brain T4ORD activity or plasma T4 levels (P
      < 0.05). However, at 1 week post injection hepatic T4ORD activity was increased
      and plasma T3 levels lowered by PCB 77 (5 and 25 ng/g), while hepatic IRD
      activity was increased by PCB 126 (50 and 500 ng/g). Neither PCB 77, PCB 126 nor
      selected hydroxylated. PCBs given in vitro compared with T4 for binding sites on
      plasma proteins or altered hepatic deiodination activity, indicating no direct
      action on plasma proteins or deiodinases We conclude that plaice TH deiodination
      tissue distribution and characteristics resemble those of other teleosts.
      Deiodination activities are low at natural assay temperatures but at 1 week show
      some responses to PCBs 77 and 126.

PMID- 11246511
TI  - Abnormal hepatic sinusoidal bile acid transport: new insights into the
      pathogenesis of cholestasis?

PMID- 11246512
TI  - Helicobacter species identified in liver from patients with cholangiocarcinoma
      and hepatocellular carcinoma.

PMID- 11246513
TI  - Helicobacter pylori infection and gastric cancer.

PMID- 11246514
TI  - Variability of serologic testing for H. pylori using U.S. and Peruvian antigens.

PMID- 11246515
TI  - Image of the month. Pheochromocytoma.

PMID- 11246516
TI  - On stratification, minimization and protection against types 1 and 2 error.

PMID- 11246518
TI  - Proceedings of the International Symposium on Probiotics and Prebiotics. Kiel,
      Germany, June 11-12, 1998.

PMID- 11246517
TI  - Acknowledgement and corrections for flawed data.

PMID- 11246519
TI  - 52nd Annual Conference of the Cardiology Society of India. December 7-10, 2000,
      Chennai. Abstracts.

PMID- 11246520
TI  - International Anesthesia Research Society 75th Clinical and Scientific Congress.
      Fort Lauderdale, Florida, USA. March 16-20, 2001. Abstracts.

PMID- 11246521
TI  - [XXXVI National Congress of the Spanish Society of Cardiology. Granada, 18-21
      October 2000. Abstracts].

PMID- 11246522
TI  - 9th Congress of the European Academy of Dermatology and Venereology. 11-15
      October 2000. Geneva, Switzerland. Abstracts.

PMID- 11246523
TI  - Annual Conference of the British Association of Sport and Exercise Sciences. 29
      August-1 September 2000, United Kingdom. Abstracts.

PMID- 11246524
TI  - XXIII International Congress of the International Academy of Pathology and 14th
      World Congress of Academic and Environmental Pathology. 15-20 October 2000.
      Nagoya, Japan. Abstracts.

PMID- 11246525
TI  - NordTox 2001, 6th Nordic Conference of the Nordic Societies of Toxicology and
      Environmental Mutagenesis. January 24-28, 2001, Norway. Abstracts.

PMID- 11246527
TI  - 2001 ASBMT, IBMTR, ABMTR Tandem Bone Marrow Transplantation Meetings. February 15
      19, 2001. Keystone, Colorado, USA. Abstracts.

PMID- 11246526
TI  - [Pediatrics in Bosnia-Herzegovina--new trends].

PMID- 11246528
TI  - Proceedings of the 2000 Winter Conference on Plasma Spectrochemistry. Fort
      Lauderdale, Florida, USA. January 10-15, 2000.

PMID- 11246529
TI  - Influence of contact system deficiencies during cardiopulmonary bypass.

PMID- 11246530
TI  - MHC class II and III polymorphisms and the antiphospholipid syndrome.

PMID- 11246531
TI  - High molecular weight kininogen deficiency: a patient who underwent cardiac
      surgery.
AB  - A 66 year old male, referred for cardiac surgery, was found to have high
      molecular weight kininogen deficiency (activity <1%). Apart from activated
      partial thromboplastin time (APTT) >300 s, tests of haemostasis were otherwise
      normal (factors VIII, IX, XI, XII and prekallikrein). No inhibitor of coagulation
      was found. The activated coagulation time (ACT) was 800 s pre-operatively and
      >1000 s after heparin. Heparin levels were measured directly by an anti-Xa
      chromogenic assay, with values of between 2.9 and 3.2 u/ml during cardiopulmonary
      bypass. Thrombin-antithrombin levels rose from 2.3*g/l before surgery to a peak
      of 83.5*g/l at the end of cardiopulmonary bypass. Cross linked fibrin d-dimers
      (XDP) levels rose from 100 ng/ml before operation to 600 ng/ml after protamine
      administration. The patient had no excess bleeding and no thrombotic
      complications from surgery. This patient shows that high molecular weight
      kininogen is not required for thrombin formation or fibrinolysis during cardiac
      surgery and illustrates the need to measure heparin directly in patients with
      such contact factor deficiencies.

PMID- 11246533
TI  - Thrombin induces the release of angiopoietin-1 from platelets.
AB  - Blood platelets contain angiopoietin-1, a growth factor essential for blood
      vessel development via stabilization of proliferating endothelial cells. It has
      recently been reported that angiopoietin-1 can act as a vascular stability factor
      (Nature Medicine 6:460, 2000). In investigating the normal tissue distribution of
      angiopoietin-1 from surgically-removed frozen specimens by RT-PCR, we found it
      consistently present in platelets and megakaryocytes, usually absent in
      relatively non-vascular tissue: breast, colon, lung, skin, kidney, thyroid,
      testicle, cervix and occasionally present in tissue enriched with vasculature:
      prostate, endometrium, ovary, under conditions in which mRNA stability was
      verified by the positive detection of internal control, actin mRNA. The
      consistent distribution in platelets and relatively absent distribution in non
      vascular normal tissue suggested that the well-known role of platelets in
      maintaining vascular stability, may in part be due to platelet release of
      angiopoietin-1 following platelet activation. In this communication we report the
      incidence of Ang-1 in various normal tissues and demonstrate that thrombin
      treated human platelets release angiopoietin-1 in vitro.

PMID- 11246534
TI  - An update of the Grutzbalg  hypothesis: the role of thrombosis and coagulation in
      atherosclerotic progression.
AB  - The Grutzbalg analogy has obviously held up and been greatly extended by current
      work implicating specific molecules in inflammation and proteolysis. Still,
      Virchow's explanation is only partly able to account for the chronic outcome of
      this disease. Many of the open questions center on fibrin. For example, we do not
      know why fibrin forms in Virmani's eroded lesions. If the source of tissue factor
      in erosion is Nemerson's "stealth" particles, we may also need to rethink the
      source of tissue factor in plaque rupture. At the other extreme, as we all know,
      atherosclerotic vascular disease is a chronic disease. While multiple episodes of
      plaque rupture are likely to be important in this chronic process, the critical
      events here--scarring, narrowing of the lumen--remain largely unexplained. The
      data reviewed here suggest that intramural coagulation could be a critical
      process underlying these chronic changes.

PMID- 11246532
TI  - Plasma tumor necrosis factor alpha levels and the -238*A promoter polymorphism in
      patients with antiphospholipid syndrome.
AB  - OBJECTIVES: To explore the possible involvement of the proinflammatory and
      prothrombotic cytokine TNFalpha in APS by determining the plasma levels in
      patients and to test for association of TNFA promoter polymorphisms and HLA class
      II genotypes with both plasma TNFalpha and disease. PATIENTS AND METHOD: We
      studied 83 Caucasoid patients with APS and two groups of healthy controls.
      TNFalpha levels were determined in plasma from 35 patients' and 21 controls using
      a highly sensitive sandwich ELISA. The full patient group was genotyped together
      with 95 ethnically matched healthy controls. -308 and -238 TNFA promoter
      polymorphisms were assessed by ARMS-PCR. HLA-DQB1, DQA1 and DRB1 genotypes were
      determined by PCR using sequence specific primers. RESULTS: TNFalpha levels were
      significantly higher in patients with APS than healthy controls (median 2.95
      pg/ml [range 0.51-10.75] vs. 0.95 pg/ml [0.51-1.6], respectively; p = 0.0001).
      Frequencies of TNFA-308*2 genotype did not differ between patients and controls.
      In contrast, TNFA-238*A positive genotype was more frequent in APS patients with
      arterial thrombosis and pregnancy loss than in controls (OR 3.7 [95% CI 1.37
      10.1], p = 0.007 and OR 3.95 [95% CI 1.3-11.7], p = 0.01; respectively).
      DQB1*0303-DRB1*0701 haplotype was associated with TNFA-238*A in the control group
      (OR 96.0 [95% CI 9.6-959], p <0.0001) as well as in APS patient's group (OR 54.2
      [95% CI 9.6-306.5], p <0.0001). CONCLUSIONS: Raised plasma TNFalpha levels were
      found in patients with APS. As a prothrombotic and proinflammatory cytokine,
      TNFalpha may be involved in the development of clinical features of APS. The lack
      of correlation between the TNFA-238 polymorphism and plasma levels associated
      with disease suggests that the TNF genetic marker may only indirectly relate to
      protein levels by virtue of allelic association with a functional marker which
      may reside in the HLA class II region.

PMID- 11246535
TI  - Symptomatic onset of severe hemophilia A in childhood is dependent on the
      presence of prothrombotic risk factors.
AB  - It has been recently suggested that the clinical phenotype of severe hemophilia A
      (HA) is influenced by co-inheritance with the factor V G1691A mutation. We
      therefore investigated 124 pediatric PUP patients with hemophilia (A: n = 111)
      consecutively admitted to German pediatric hemophilia treatment centers. In
      addition to factor VIII activity, the factor V (FV) G1691A mutation, the
      prothrombin (PT) G20210A variant, antithrombin, protein C, protein S and
      antithrombin were investigated. 92 out of 111 HA patients (F VIII activity < 1%)
      were suffering from severe HA. The prevalence of prothrombotic risk factors in
      children with severe HA was no different from previously reported data: FV G1691A
      6.5%, PT G20201A 3.2%, and protein C type I deficiency 1.1%. No deficiency states
      of antithrombin or protein S were found in this cohort of hemophilic patients.
      The first symptomatic bleeding leading to diagnosis of severe hemophilia (< 1%)
      occurred with a median (range) age of 1.6 years (0.5-7.1) in children carrying
      defects within the protein C pathway or the PT gene mutation compared with non
      carriers of prothrombotic risk factors (0.9 years (0.1-4.0; p = 0.01). The
      cumulative event-free bleeding survival was significantly prolonged in children
      carrying additionally prothrombotic defects (log-rank/Mantel-Cox: p = 0.0098). In
      conclusion, data of this multicenter cohort study clearly demonstrate that the
      first symptomatic bleeding onset in children with severe HA carrying
      prothrombotic risk factors is significantly later in life than in non-carriers.

PMID- 11246536
TI  - Treatment with simvastatin and low-dose aspirin depresses thrombin generation in
      patients with coronary heart disease and borderline-high cholesterol levels.
AB  - Aspirin and statins are beneficial in coronary heart disease across a broad range
      of cholesterol levels. We assessed the effects of low-dose aspirin (75 mg daily)
      on thrombin generation in patients with coronary heart disease and average blood
      cholesterol levels. We also investigated whether in patients with borderline-high
      cholesterol level who have been already taking aspirin, additional treatment with
      simvastatin would affect thrombin generation. Seven-day treatment with low-dose
      aspirin decreased thrombin generation ex vivo only in patients with total
      cholesterol < or = 5.2 mmol/L. In patients with higher cholesterol levels aspirin
      had no effect. In these patients, already taking low-dose aspirin, additional
      three-month simvastatin treatment resulted in a reduction of thrombin generation.
      This demonstrates that low-dose aspirin depresses thrombin generation only in
      subjects with desirable blood cholesterol levels, while in others, with
      borderline-high cholesterol, thrombin formation is being reduced following the
      addition of simvastatin.

PMID- 11246537
TI  - Lack of association between the platelet glycoprotein Ia C807T gene polymorphism
      and myocardial infarction in Japanese. An approach entailing melting curve
      analysis with specific fluorescent hybridization probes.
AB  - The platelet-collagen receptor, glycoprotein Ia/IIa (integrin alpha2beta1) plays
      a fundamental role in the adhesion of platelets to fibrillar collagen, an event
      leading to platelet activation and thrombus formation and contributing to the
      pathogenesis of thrombotic disease. Further, glycoprotein Ia/IIa receptor density
      and function may be associated with two linked and silent polymorphisms (807C/T
      and 873G/A) within the glycoprotein Ia gene. We tested the extent to which these
      polymorphisms serve as genetic markers of myocardial infarction in a Japanese
      population. A case-control study was carried out using 210 Japanese myocardial
      infarction patients and 420 age- and sex-matched controls. Genotyping was
      accomplished using PCR followed by melting curve analysis with specific
      fluorescent hybridization probes. The 807CC, CT, TT genotypes linked perfectly to
      the 873GG, GA, AA genotypes, respectively. Allele frequencies of the 807T (873A)
      variant were similar in the control and patient groups (0.373 vs. 0.352). The
      807T and 873A variants of platelet glycoprotein Ia gene are common and in a
      perfect linkage in the Japanese population, but it appears unlikely that the 807T
      (873A) variant represents a useful marker of increased risk for myocardial
      infarction.

PMID- 11246538
TI  - The E27 beta2-adrenergic receptor polymorphism reduces the risk of myocardial
      infarction in dyslipidemic young males.
AB  - In the present study we evaluated whether two polymorphisms of beta2-adrenergic
      receptors (beta2-AR) gene (R16G and Q27E) could modify the risk of myocardial
      infarction (MI). Using a case-control design, we analyzed the data from 125 male
      patients who had experienced a first episode of MI before the age of 45 years and
      108 male controls matched for age. The allele frequencies for R16G and Q27E were:
      G16=0.56 and E27=0.36 in patients with MI and G16=0.61 and E27=0.42 in the
      control group. There was a trend (not statistically significant) of decreasing MI
      risk according to E27 or G16 alleles. Combined effect between E27 allele and
      history of dyslipidemia has been observed. Whereas dyslipidemia conferred a
      relative risk of MI of 4.8 (P<0.001) compared with normolipidemia in the entire
      study population, the relative risk increased to 9.0 (P<0.001) in Q27 homozygotes
      with dyslipidemia, and decreased to 1.8 (P=0.36) in E27 homozygotes. Our results
      show that the E27 allele of the beta2-adrenergic receptor has a significant
      protective effect on MI in dyslipidemic young male.

PMID- 11246539
TI  - Activation products of the haemostatic system in coronary, cerebrovascular and
      peripheral arterial disease.
AB  - To determine the presence of a 'hypercoagulable state' as assessed by indices of
      thrombin and plasmin generation and of the amount of fibrin that is lysed, in
      patients with stable coronary, cerebral and peripheral arterial disease a
      population-based cross-sectional study was performed. From a population-based
      cohort comprising 7983 men and women aged 55 years and over, we randomly selected
      127 subjects with a history of myocardial infarction, 124 with a history of
      stroke and/or transient ischemic attack, 131 patients with peripheral arterial
      disease and 263 control subjects in the same age group without arterial disease.
      Subjects using anticoagulant drugs were not selected. F1+2, TAT, and PAP were not
      associated with a history of cardiovascular events, nor with peripheral arterial
      disease. In contrast, positive associations were found for D-Dimer. Mean D-Dimer
      level was 40 microg/l (95% CI 35, 44) in control subjects; 53 microg/l (47, 61)
      in those with a history of myocardial infarction and 51 microg/l (45, 58) in
      those with a history of stroke and or transient ischemic attack. D-Dimer
      increased gradually with increasing severity of peripheral atherosclerosis; a
      decrease in ankle/arm systolic blood pressure ratio of 0.1 was associated with an
      increase in D-Dimer of 3.9 microg/l (p<0.01). This was more pronounced in
      subjects with higher F1+2, TAT and PAP concentration. In conclusion, the markers
      of onset of coagulation F1+2, TAT and PAP are not associated with the presence of
      arterial disease, but increased levels of these markers are necessary for the
      positive association between D-Dimer and arterial disease.

PMID- 11246540
TI  - Tissue factor pathway inhibitor (TFPI) levels in the plasma and urine of children
      with meningococcal disease.
AB  - Tissue factor pathway inhibitor (TFPI) is a potent inhibitor of the TF-dependent
      coagulation system. In meningococcal disease, up-regulation of tissue factor
      expression on blood monocytes and possibly on endothelial cells has the potential
      to trigger the activation of the TF-dependent pathway of coagulation.
      Intravascular coagulation is considered to be a major pathogenic factor in
      meningococcal disease. We postulated that imbalance between TF expression and
      TFPI concentration might lead to uncontrolled coagulation in meningococcal
      disease. The aim of this study was to assess the levels of total TFPI in the
      plasma of patients with meningococcal disease and assess whether increased
      leaking of the TFPI was occurring. TFPI antigen levels and activity were measured
      in the plasma of 54 patients with meningococcal disease, and 13 healthy control
      children. TFPI antigen level were also determined in the urines of 14 of the 54
      and 9 healthy control children. Plasma TFPI activity was reduced in the
      meningococcal diseased patients (mean of 0.503 +/- 0.341 U/ml; control, 1.010 +/-
      0.199 U/ml: p <0.0001), as was the TFPI antigen levels (mean of 54.85 +/- 35.05
      ng/ml; Control, 94.51 +/- 11.44 ng/ml; p <0.0001). In contrast, TFPI antigen
      levels were increased in the urine of these patients when compared to the levels
      found in the urine of the healthy control children (mean of 12.96 +/- 5.392
      ng/mmol creatinine; Control, 0.239 +/- 0.191 ng/mmol creatinine; p <0.035). A
      lack of correlation between TFPI-activity and TFPI-antigen plasma levels was
      observed (r = 0.002, p = 0.85). This data is consistent with the hypothesis that
      in meningococcal disease there is increased inactivation of plasma TFPI by the up
      regulation of tissue factor expression but in addition increased clearance of
      TFPI in urine is occurring.

PMID- 11246541
TI  - Prothrombotic changes in hemostatic parameters and C-reactive protein in the
      elderly with winter acute respiratory tract infections.
AB  - Mortality rates attributable to cerebrovascular and ischemic heart disease
      increase among older adults during the winter. Prothrombotic changes in the
      hemostatic system related to seasonal factors, such as ambient temperature
      changes, and winter acute respiratory tract infections, may contribute to this
      excess seasonal mortality. A prospective nested case-control study was conducted
      to assess the impact of winter acute respiratory tract infections on fibrinogen,
      factor VII, factor VIIa, D-dimer, prothrombin fragment 1.2, PAI-1, soluble P
      selectin and C-reactive protein (CRP) in older adults. The change in laboratory
      parameters from baseline (fall) to the time of infection in both middle-aged and
      elderly individuals was compared with matched non-infected controls. In older
      adult participants with winter acute respiratory tract infections, significant
      increases occurred in fibrinogen and C-reactive protein, but not in any other
      markers. The mean fibrinogen increased 1.52 g/L (38%) and the mean CRP increased
      37 mg/L (370%) over baseline (both p <0.001). In a multivariate analysis, both
      infection and season were associated with the increase in fibrinogen, but only
      infection was associated with the CRP increase. Old age magnified the increase in
      CRP but not in fibrinogen. Winter acute respiratory tract infections induce an
      exaggerated inflammatory response in older adults. The associated increase in
      fibrinogen, an independent risk factor for ischemic heart disease, may be partly
      responsible for the excess winter vascular mortality.

PMID- 11246542
TI  - Whole blood tissue factor procoagulant activity remains detectable during severe
      aplasia following bone marrow and peripheral blood stem cell transplantation.
AB  - Using a novel whole blood assay, we recently demonstrated that tissue factor
      procoagulant activity (TF PCA) is present in normal individuals. Preliminary
      experiments suggested that this activity is localized in the mononuclear cell
      fraction. Postulating that whole blood TF PCA would therefore be undetectable
      when monocytes and neutrophils are absent from peripheral blood, we assayed TF
      PCA during the peri-transplant period in 15 consecutive patients undergoing
      allogeneic (n = 12) or autologous (n = 3) bone marrow transplantation (BMT) or
      peripheral blood stem cell transplantation (PBSCT). Baseline (pre-transplant)
      mean TF PCA was higher in patients compared to normal controls (P <0.005).
      Unexpectedly, although TF PCA during the period of profound aplasia was
      significantly reduced compared to baseline (p <0.05), fully 55% of the initial
      activity remained detectable. During the engraftment phase, TF PCA returned to
      pre-transplant levels, with a linear correlation between monocyte counts and TF
      PCA (r = 0.63). In contrast to normal whole blood, incubation of aplastic samples
      with E. Coli lipopolysaccharide ex vivo failed to induce TF PCA. Throughout the
      period of study--but especially during the aplastic phase--the absolute number of
      circulating endothelial cells (CECs) that were TF antigen-positive was increased
      compared to normals (P <0.001). However, removal of these cells from whole blood
      samples failed to significantly diminish total TF PCA indicating that CECs alone
      could not account for the detectable TF PCA during aplasia. We conclude that
      neither circulating mature myelo-monocytic cells nor endothelial cells can
      account for all the functionally intact TF in peripheral blood. Further studies
      are needed to identify the other source(s) of TF PCA.

PMID- 11246543
TI  - Interaction of heritable and estrogen-induced thrombophilia: possible etiologies
      for ischemic optic neuropathy and ischemic stroke.
AB  - Our specific aim was to assess how thrombophilic exogenous estrogens interacted
      with heritable thrombophilias leading to non-arteritic ischemic optic neuropathy
      (NAION) and ischemic stroke. Coagulation measures were performed in a 74 year old
      patient and her immediate family. The proband had a 47 year history of 9 previous
      thrombotic episodes, and developed unilateral NAION 4 years after starting
      estrogen replacement therapy (ERT). The proband was heterozygous for two
      thrombophilic gene mutations (G20210A prothrombin gene, platelet glycoprotein
      IIIa P1A1/A2 polymorphism), and homozygous for the C677T mutation in the
      methylenetetrahydrofolate reductase (MTHFR) gene. Of 238 normal controls, none
      had these 3 gene mutations together. The proband's mother and brother had deep
      venous thrombosis (DVT). The proband's brother, sister, nephew, daughter, and two
      granddaughters were homozygous for the C677T MTHFR mutation. The proband's
      brother was heterozygous for the G20210A prothrombin gene mutation. The proband's
      niece was heterozygous for the G20210A prothrombin gene mutation, homozygous for
      the C677T MTHFR mutation, homozygous for the hypofibrinolytic 4G polymorphism of
      the plasminogen activator inhibitor-1 (PAI-1) gene, and heterozygous for the
      platelet glycoprotein IIIa P1A1/A2 polymorphism. Of 238 normal controls, none had
      the niece's combination of 4 gene mutations. When ERT-mediated thrombophilia was
      superimposed on the proband's heritable thrombophilias, unilateral ischemic optic
      neuropathy developed, her tenth thrombotic event over a 5 decade period. When
      estrogen-progestin oral contraceptives were given to the proband's niece, she had
      an ischemic stroke at age 22. Exogenous estrogen-mediated thrombophilia
      superimposed on heritable thrombophilia and hypofibrinolysis is associated with
      arterial and venous thrombi, and appears to be a preventable, and potentially
      reversible etiology for ischemic optic neuropathy and ischemic stroke.

PMID- 11246544
TI  - Factor VIII Arg2304 --> His binds to phosphatidylserine and is a functional
      cofactor in the factor X-ase complex.
AB  - Four factor VIII light chain constructs containing hemophilia A mutations at
      R2304 and R2307 were prepared and expressed in mammalian cells. These mutations
      are located in a putative phosphatidylserine binding site identified by peptide
      studies (spanning amino acids 2303-2332). The levels of all four mutants in
      conditioned medium were significantly less than wild type by immunoprecipitation
      and ELISA. R2304H and wild type factor VIII light chains were concentrated by
      cation exchange chromatography from medium. R2304H and wild type factor VIII
      light chains bound immobilized phosphatidylserine similarly. The reconstituted
      cofactor activity of R2304H factor VIII light chain was slightly greater than
      wild type factor VIII light chain. These results are consistent with the recently
      reported crystal structure of factor VIII C2 domain that suggests R2304H is not
      directly involved in phospholipid binding. The observed clinical phenotype is
      probably due to decreased circulating levels of a functional protein.

PMID- 11246545
TI  - F X Nottingham and F X Taunton. Two novel mutations in factor X resulting in loss
      of functional activity and an interpretation using molecular modelling.
AB  - We report two novel mutations in the Factor X gene which result in a bleeding
      tendency in two unrelated Caucasian families. Although the mutations occur at
      adjacent codons in exon 8 and result in reduced functional activity with normal
      antigen levels, the patterns of inheritance appear to be quite distinct. Factor X
      Nottingham (alanine 404 threonine) appears to be associated with an autosomal
      recessive pattern of inheritance. In contrast, Factor X Taunton (arginine 405
      glycine) results in a mode of inheritance consistent with an autosomal dominant
      pattern, all five of the heterozygotes in this family being clinically affected.
      Molecular modelling studies suggest that, in the case of Factor X Nottingham, a
      drastic conformational change causes major unfolding of the protein. For Factor X
      Taunton, less extreme conformational changes occur causing loss of functional
      activity such that substrate binding sites might be maintained. It is proposed
      that competition with wild type for substrate binding could occur leading to a
      dominant negative effect.

PMID- 11246546
TI  - Factor V Arg306 --> Gly mutation is not associated with activated protein C
      resistance and is rare in Taiwanese Chinese.
AB  - Polymerase chain reaction amplification followed by BstOI enzyme digestion and
      DNA sequencing was employed to detect the mutation of factor V gene. The subjects
      consisted of 105 venous thrombophilic patients and 183 healthy controls. Only one
      patient was found to have factor V Arg306 --> Gly mutation, his elder son also
      had an identical mutation. None of the healthy subjects studied had Arg306 -->
      Thr mutation. The rare event of factor V Arg306 --> Gly mutation in patients and
      controls suggest that this mutation is not associated with increased risk of
      venous thrombosis. Conventional, modified and extended activated protein C (APC)
      resistance assays in this patient and his family members clearly showed that
      factor V Arg306 --> Gly mutation is not associated with APC resistance (APC
      sensitivity ratio <2). In conclusion, factor V Arg306 --> Gly mutation is rare in
      Taiwanese Chinese and not associated with APC resistance, it is possibly not a
      risk factor for venous thrombophilic thrombosis.

PMID- 11246547
TI  - Anticoagulant dysfunction of human Arg352Trp-activated protein C caused by
      defective factor Va inactivation.
AB  - The dysfunctional mutant R352W-protein C was found in two patients with venous
      thrombosis. The mutant R352A-protein C was constructed to define the contribution
      of charge/size of the residue at 352 on protein C (chymotrypsin numbering 187).
      Compared with wild type-protein C, R352W-protein C showed no difference in
      activation by thrombin-thrombomodulin or alpha-thrombin. However, R352W-activated
      protein C (APC) anticoagulant activity (aPTT assay) was reduced to approximately
      65%. Although the catalytic efficiency of R352W-APC towards the oligopeptide
      substrate S-2366 was unperturbed, factor Va and R506Q-factor Va were not
      efficiently inactivated by R352W-APC compared with wild type-APC. R352A-APC
      showed reduced anticoagulant activity and reduced efficiency in factor Va
      inactivation and in factor VIIIa-inactivation in the presence of protein S. These
      observations suggest that the dysfunction of R352W-APC in factor Va inactivation
      may be one of the mechanisms leading to venous thrombosis in affected patients
      and that R352 plays an important role in the physiological functioning of APC.

PMID- 11246548
TI  - Effects of diets containing olive oil, sunflower oil, or rapeseed oil on the
      hemostatic system.
AB  - Various studies have already shown that the fatty acid composition of dietary fat
      has different effects on hemostasis and platelet function. However, knowledge on
      this topic is incomplete. In the present study, fifty-eight healthy students
      received either a 4-week rapeseed oil [high content of monounsaturated fatty
      acids (MUFA) and high n-3/n-6 PUFA ratio], an olive oil (high content of MUFA,
      low n-3/n-6 PUFA ratio) or a sunflower oil (low content of MUFA, low n-3/n-6 PUFA
      ratio) diet. In each group, effects on hemostatic parameters were compared with a
      wash-in diet rich in saturated fatty acids with respect to intermediate-time
      effects on the hemostatic system and platelet function. With the olive oil diet,
      a reduction of coagulation factors VIIc, XIIc, XIIa, and Xc was found, whereas
      sunflower oil led to lower values of coagulation factors XIIc, XIIa, and IXc. In
      all study groups levels of plasmin-alpha2-antiplasmin were lower in week 4 than
      at baseline. Lower fibrinogen binding on platelets was found after the sunflower
      oil diet, whereas expression of CD62 and spontaneous platelet aggregation were
      slightly higher after the olive oil diet. However, given the major differences in
      the fatty acid compositions of the diets, the differences between the groups with
      respect to hemostasis tended to be small. Therefore, the clinical significance of
      the present findings remains to be evaluated.

PMID- 11246549
TI  - Beneficial effect of the active form of vitamin D3 against LPS-induced DIC but
      not against tissue-factor-induced DIC in rat models.
AB  - 1Alpha,25-dihydroxyvitamin D3 (active form of vitamin D3; vitamin D3) has been
      reported to induce the upregulation of thrombomodulin and downregulation of
      tissue factor (TF) on monocytes. The possibility exists that vitamin D3 prevents
      the development of disseminated intravascular coagulation (DIC). In particular,
      monocyte TF production plays an important role in the pathophysiology of DIC in
      septic patients. We have attempted to determine whether vitamin D3 is effective
      against DIC in a rat model induced by lipopolysaccharides (LPS) (30 mg/kg, 4 h)
      or TF (3.75 U/kg, 4 h) using selective hemostatic parameters, markers of organ
      dysfunction and pathological findings (assessment of glomelular fibrin
      deposition). Vitamin D3 was administered orally each day at a dose of 2.0
      mg/kg/day for 3 days, or low molecular weight heparin (LMWH 200 u/kg; i.v.) was
      given 10 min before the injection of TF or LPS in each treatment group. Vitamin
      D3 was effective against DIC in the rat model induced by LPS only, whereas LMWH
      was effective against DIC in both rat models induced by either TF or LPS. The
      anti-DIC effect of vitamin D3 was equal to (or more potent than) that of LMWH.
      The results suggested that vitamin D3 was useful for the treatment of LPS-induced
      DIC, and that the assessment of a drug's efficacy should be done carefully given
      the markedly different results obtained according to the agents used to induce
      DIC.

PMID- 11246550
TI  - Multicenter study of homocysteine measurement--performance characteristics of
      different methods, influence of standards on interlaboratory agreement of
      results.
AB  - After the demonstration that moderate hyperhomocysteinemia is associated with
      thrombosis, many hematological labs are becoming interested in total homocysteine
      (tHcy) measurement. This prompted us to organize a collaborative study to
      investigate the performance of methods used in this setting and to assess the
      between-lab comparability of results. Two pairs of pooled plasma (A1-A2 and B1
      B2) were prepared at the coordinating Center. tHcy levels were normal in A1-A2
      and moderately high in B1-B2. Within each pair tHcy levels were similar but not
      identical. Aliquots were taken from each pool to prepare sets of 100 samples
      (coded from 1 to 100). Each set consisted of 25 replicates for each pool. Samples
      were frozen and shipped in dry ice to 16 labs with a common frozen aqueous
      standard. Labs were asked to measure (in blind) tHcy with their methods and
      standards. Results were sent to the coordinating Center both as raw readings and
      as tHcy levels. The following methods were used: High Pressure Liquid
      Chromatography (HPLC) in 12 labs (home-made in 10 and commercial in 2); Enzyme
      Immuno Assays (EIA) in 2; Fluorescence Polarization Immunoassay (FPIA) in 2 and
      Capillary Electrophoresis (CE) in one. Results for paired pools (A1-A2 and B1-B2)
      were analyzed by the Student t test to assess for the ability to discriminate
      between similar but not identical tHcy levels. Results for each pool were used to
      assess within-lab reproducibility and between-lab comparability. Within-lab
      reproducibility expressed as median CV ranged from 12.6 to 13.9% (home-made
      HPLC); from 9.2 to 11.4% (commercial HPLC); from 21.8 to 24.2% (EIA); from 2.7 to
      3.3% (FPIA) and from 11.2 to 22.0% (CE). All labs, except one using CE and 2
      using home-made HPLC, were able to discriminate between similar tHcy levels in
      the normal range (pools A1-A2). Ten labs (4 using home-made HPLC, 2 commercial
      HPLC, 2 FPIA, one EIA and one CE) were able to discriminate between similar
      moderately high tHcy levels (pools B1-B2). Between-lab comparability expressed as
      CV was 14.0% 13.9%, 15.6% and 14.5% for pools A1, A2, B1, and B2. These values
      were considerably lower (CV values < 5.2%) when a common plasma standard was used
      for calculation of tHcy levels, while the use of a common aqueous standard failed
      to achieve the necessary harmonization. In conclusion, performance
      characteristics of the FPIA method compare favorably with the well-established
      HPLC methods. It is simpler and more suitable to be used by general hematological
      labs. Between-lab comparability of results is still a problem. The establishment
      of an international plasma standard would be of help to harmonize tHcy
      measurement across laboratories.

PMID- 11246552
TI  - Platelet shape change evoked by selective activation of P2X1 purinoceptors with
      alpha,beta-methylene ATP.
AB  - Simultaneous measurements of [Ca2+]i and light transmission were used to examine
      the relationship between P2X1 receptor activation and functional platelet
      responses. The P2X1 agonist alpha,beta-MeATP evoked a transient [Ca2+]i increase
      and a reversible decrease in light transmission; both responses required external
      Ca2+ and the nucleotidase apyrase. The transmission response was due to shape
      change only, verified by scanning electron microscopy and insensitivity to
      Reopro, a GPIIbIIIa antagonist. Alpha,beta-MeATP stimulated smaller shape changes
      than ADP, however P2X1 responses had a lifespan of <2 h following resuspension in
      saline and may be considerably larger in vivo. A peak [Ca2+]i increase of >50 nM
      was required for detectable shape change. Overlap of concentration-response
      relationships for alpha,beta-MeATP-evoked [Ca2+]i and shape change suggests that
      other second messengers are not involved. Therefore, the physiological P2X1
      agonist ATP can contribute to platelet activation, in contrast to its previously
      described inhibitory action at metabotropic platelet purinoceptors.

PMID- 11246551
TI  - Vascular endothelial growth factor enhances the expression of urokinase receptor
      in human endothelial cells via protein kinase C activation.
AB  - Among other proteolytic enzymes, the urokinase-type plasminogen activator (u
      PA)/plasmin cascade contributes to cell migration and the formation of capillary
      like structures in a fibrinous exudate. The u-PA receptor (u-PAR) focuses
      proteolytical activity on the cell surface of the endothelial cell and hereby
      accelerates the pericellular matrix degradation. Vascular endothelial growth
      factor (VEGF) and fibroblast growth factor (FGF)-2 enhance u-PA receptor
      expression in human endothelial cells. In this paper we show that the protein
      kinase C (PKC) inhibitors Ro31-8220 and GF109203X inhibit VEGF165-induced u-PAR
      antigen expression in human endothelial cells, whereas PKC inhibition had no
      effect on FGF-2-induced u-PAR antigen enhancement. In addition, inhibition of PKC
      activity had no effect on VEGF165- or FGF-2-induced proliferation in human
      endothelial cells. We conclude that VEGF165 induces u-PAR via a PKC-dependent
      pathway, whereas proliferation is induced via a different pathway probably
      involving tyrosine phosphorylation of proteins downstream of the VEGF receptors.

PMID- 11246554
TI  - Beta2-glycoprotein I binding to platelet microparticle membrane specifically
      reduces immunoreactivity of glycoproteins IIb/IIIa.
AB  - We have investigated beta2-glycoprotein I (beta2GPI) binding to platelet-derived
      microparticles (PMP) and its effect on GPIIb/IIIa. PMP were isolated from washed
      human platelets after stimulation with A23187, and analyzed by surface plasmon
      resonance spectroscopy. Beta2GPI as well as activated protein C (APC) or annexin
      V bound to PMP-coated sensorchips, demonstrating exposure of anionic
      phospholipids on immobilized PMP. Beta2GPI binding was impaired by calcium and
      occurred in a concentration-dependent manner with apparent k(on) = 2.6 x 10(4) M(
      1) s(-1) and k(off) = 4.4 x 10(-3) s(-1), corresponding to a KD value of 1.7 x
      10(-7) M. When analyzed by flow cytometry, the binding of certain mAbs specific
      for GPIIb and/or GPIIIa was reduced in the presence of beta2GPI but not of APC or
      annexin V, whereas the binding of anti-GPIb or anti-P-selectin mAbs, or of
      soluble fibrinogen remained unchanged. These results suggest a broad but specific
      influence of beta2GPI on GPIIb/IIIa immunoreactivity, and indicate that beta2GPI
      may act as a modulator of GPIIb/IIIa-dependent functions of PMP.

PMID- 11246553
TI  - Time and dose dependent augmentation of inhibitory effects of abciximab by
      aspirin.
AB  - Aspirin and abciximab independently decrease the incidence of cardiac events. To
      identify potential interactions, antiplatelet effects of abciximab were
      characterized in blood from healthy subjects given aspirin. Platelet activation
      was determined in whole blood with and without abciximab (2 microg/ml) added in
      vitro. Flow cytometry was used to quantify fibrinogen binding (glycoprotein IIb
      IIIa activation). Binding of fluorochrome-labeled and 125I-labeled abciximab was
      determined before and after exposure to aspirin. In blood from subjects given
      aspirin for 5 days, abciximab-induced inhibition of the capacity to bind
      fibrinogen in response to 1 microM ADP was greater when the daily dose had been
      325 mg compared with 81 mg (% inhibition: no aspirin 53 +/- 6; 81 mg daily 62 +/-
      5; 325 mg daily 69 +/- 6). The effect of 5 daily doses of aspirin was greater
      than that of one. Larger single doses elicited larger effects (% inhibition 2 h
      after 325 mg 59 +/- 6; 2 h after 650 mg 78 +/- 5). Neither salicylsalicylic acid
      nor naproxen sodium potentiated the effect of abciximab. Exposure of platelets to
      14C-acetylsalicylic acid led to acetylation of glycoprotein IIb and IIIa. Binding
      of 125I-abciximab to platelets was increased after 30 and 60 min. Acetylation of
      glycoprotein IIb-IIIa by aspirin augments inhibitory effects of abciximab in a
      dose- and time-dependent manner by increasing binding of abciximab to platelets.

PMID- 11246555
TI  - Evidence for platelet alphaIIb beta3 activation despite elevated cytosolic cAMP.
AB  - Cyclic nucleotides, such as cAMP, are known to inhibit the multistep cascade that
      results in platelet aggregation. In the present study we provide evidence that it
      is possible to bypass cAMP inhibitory effect on fibrinogen binding site exposure
      induced by the thromboxane A2 synthetic analogue U46619, the snake venom toxin
      convulxin, or by the direct PKC activator OAG, by concomitantly activating a G1
      coupled receptor by means of epinephrine or by inducing cytosolic calcium influx
      by means of ionomycin. In fact, in our study we demonstrate that, in iloprost
      treated platelets, the inhibition of both platelet aggregation and fibrinogen
      binding was overcome by adding epinephrine or ionomycin. To further confirm this,
      we used the cAMP analogue dibutyryl cAMP and we obtained platelet aggregation in
      response to U46619, convulxin or OAG plus epinephrine. Moreover, a complete
      inhibition of platelet aggregation in the presence of high concentrations of cAMP
      was observed only in the case of U46619, while a small percentage of aggregation
      persisted when convulxin or OAG were used, due to the small amount of ADP that
      both convulxin and OAG are able to release. Since PKC inhibition didn't allow
      platelet aggregation to occur in response to the concomitant activation of U46619
      or convulxin, plus epinephrine or ionomycin, we can conclude that cAMP-induced
      inhibition of aggregation can be counteracted by the simultaneous activation of
      PKC in the presence of an activated G1-coupled receptor or of an induced calcium
      influx.

PMID- 11246556
TI  - Development and assessment of enzyme immunoassay for platelet-derived
      microparticles.
AB  - Platelet-derived microparticles (PMPs) are released from platelets through the
      platelet activation by high shear stress, collagen, or calcium ionophore
      (A23187). PMPs are observed in patients with acute myocardial infarction,
      thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, heparin-induced
      thrombocytopenia and other thrombotic disorders, but the importance of
      circulating PMPs in the pathogenesis of these diseases is still debated. Numbers
      of PMPs are usually determined by flowcytometry (FCM), but easier and
      reproducible PMP assay systems are needed. To develop a better ELISA for PMPs, we
      used antibodies against the platelet antigens anti-GPIb (NNKY5-5), anti
      GPIIb/IIIa (NNKY2-11, anti-CD41), anti-GPIX (KMP-9), and anti-CD9 (NNKY1-19).
      PMPs were detected with all combinations of these antibodies, but the ELISA
      having the highest and most specific absorbance was obtained with a combination
      of KMP-9 (capture antibody) and NNKY5-5 (detecting antibody). PMPs in blood
      samples were measured by ELISA and FCM. ELISA correlated with PMPs quantitated by
      FCM. By shaking ELISA plates during incubation, nonspecific binding of platelets
      was eliminated. The level of PMPs was not increased in diabetes mellitus,
      thrombotic thrombocytopenic purpura, antiphospholipid syndrome, or sepsis. The
      concentration of PMP was elevated in hemolytic uremic syndrome. Activated PMPs
      were absorbed to 0.8 microm filter, but circulating PMPs were not absorbed. These
      results suggest that activated PMPs are likely to adhere to leukocytes or
      endothelial cells at the activation site and that the circulating form of PMPs
      are likely to be a residue of activated PMPs. To detect only the activated form
      of PMPs, a new ELISA needs to be developed, and it will likely use a combination
      of antibodies that detect platelet activation markers such as P-selectin (CD62P)
      or activated GPIIb/IIIa.

PMID- 11246557
TI  - Genetic and pharmacological analyses of involvement of Src-family, Syk and Btk
      tyrosine kinases in platelet shape change. Src-kinases mediate integrin alphaIIb
      beta3 inside-out signalling during shape change.
AB  - Platelet shape change was found to be associated with an increase in protein
      tyrosine phosphorylation upon stimulation of thrombin-, ADP- and thromboxane A2-G
      protein coupled receptors in human platelets and thromboxane A2 receptors in
      mouse platelets. By using PP1 and PD173956, two structurally unrelated specific
      inhibitors of Src-family tyrosine kinases, and mouse platelets deficient in the
      Src-kinase Fyn or Lyn, we show that Src-family kinases cause the increase in
      protein tyrosine phosphorylation. We further detected that the non-Src tyrosine
      kinase Syk was activated during shape change in a manner dependent on Src-family
      kinaseactivation. The pharmacological experiments and the studies on Fyn-, Lyn-
      and Syk-deficient mouse platelets showed that neither Src-family kinases nor Syk
      are functionally involved in shape change. Also human platelets deficient of the
      tyrosine kinase Btk showed a normal shape change. Binding of PAC-1 that
      recognizes activated integrin alphaIIb beta3 complexes on the platelet surface
      was enhanced during shape change and blocked by inhibition of Src-kinases. We
      conclude that the activation of Src-kinases and the subsequent Syk stimulation
      upon activation of G-protein coupled receptors are not involved in the
      cytoskeletal changes underlying shape change of human and mouse platelets, but
      that the stimulation of this evolutionary conserved pathway leads to integrin
      alphaIIb beta3 exposure during shape change.

PMID- 11246558
TI  - Potentiation of thromboxane A2-induced platelet secretion by Gi signaling through
      the phosphoinositide-3 kinase pathway.
AB  - Platelet activation results in shape change, aggregation, generation of
      thromboxane A2, and release of granule contents. We have recently demonstrated
      that secreted ADP is essential for thromboxane A2-induced platelet aggregation
      (J. Biol. Chem. 274: 29108-29114, 1999). The aim of this study was to investigate
      the role of secreted ADP interacting at P2 receptor subtypes in platelet
      secretion. Platelet secretion induced by the thromboxane A2 mimetic U46619 was
      unaffected by adenosine-3'phosphate-5'-phosphate, a P2Y1 receptor selective
      antagonist. However, AR-C66096, a selective antagonist of the P2T(AC) receptor,
      inhibited U46619-induced platelet secretion, indicating an important role for Gi
      signaling in platelet secretion. Selective activation of either the P2T(AC)
      receptor or the alpha2A adrenergic receptor did not cause platelet secretion, but
      potentiated U46619-induced platelet secretion. SC57101, a fibrinogen receptor
      antagonist, failed to inhibit platelet secretion, demonstrating that outside-in
      signaling was not required for platelet secretion. Since Gi signaling results in
      reduction of basal cAMP levels through inhibition of adenylyl cyclase, we
      investigated whether this is the signaling event that potentiates platelet
      secretion. SQ22536 or dideoxyadenosine, inhibitors of adenylyl cyclase, failed to
      potentiate U46619-induced primary platelet secretion, indicating that reduction
      in cAMP levels does not directly contribute to platelet secretion. Wortmannin, a
      selective inhibitor of PI-3 kinase, minimally inhibited U46619-induced platelet
      secretion when it was solely mediated by Gq, but dramatically ablated the
      potentiation of Gi signaling. We conclude that signaling through the P2T(AC)
      receptor by secreted ADP causes positive feedback on platelet secretion through a
      PI-3 kinase pathway.

PMID- 11246559
TI  - Purification of proplatelet formation (PPF) stimulating factor:
      thrombin/antithrombin III complex stimulates PPF of megakaryocytes in vitro and
      platelet production in vivo.
AB  - In this study, the protein which stimulates proplatelet formation (PPF) of
      megakaryocytes was purified from normal human plasma using 7 steps procedures.
      Two different protease inhibitors were identified based on their amino acid
      sequences, i.e. antithrombin III (AT III) and C1 inhibitor. They were included in
      high density lipoprotein (HDL). HDL was necessary for AT III to be active in PPF
      in vitro. The biological effects of the AT III/HDL or thrombin-AT III (TAT)/HDL
      were studied in vitro. PPF of murine megakaryocytes was stimulated by negative
      control (BSA) (1.8 +/- 0.3%), AT III (2.0 +/- 0.4%), HDL (1.2 +/- 0.9%), AT
      III/HDL (14.8 +/- 2.1%) or TAT/HDL (23.3 +/- 3.5%), respectively. TAT/HDL also
      had a synergistic effect with the mpl ligand, judging by the acetylcholinesterase
      (AchE) expression of murine megakaryocytes (2.7 fold increase). In vivo
      subcutaneous administration of AT III alone or TAT for 3 days significantly
      stimulated thrombocytosis (136% and 144%, respectively, p<0.05) and AT III/HDL
      showed rapid and further stimulation (150%, p <0.01). These results and the
      previous studies indicate that megakaryocytopoiesis is regulated by the mpl
      ligand, while a protease/protease inhibitor complex such as TAT, which is
      involved in the coagulation cascade associated with platelet consumption, might
      be one of the regulators in platelet production.

PMID- 11246560
TI  - Expression and anticoagulant function of the endothelial cell protein C receptor
      (EPCR) in cancer cell lines.
AB  - Induction of procoagulant factors in malignant cells is considered to be the
      major cause of coagulation disorders in cancer. Thrombomodulin (TM), a negative
      regulator of coagulation was also found to be expressed in cancer cells. We
      report here evidence for another anticoagulant, the endothelial cell protein C
      receptor (EPCR), in cancer cells. EPCR was detected in several cell lines derived
      from various types of cancer. Significant levels of protein C (PC) activation
      were detected only with cell lines expressed both EPCR and TM. Anti-EPCR
      monoclonal antibodies (mAbs) specifically inhibited the activation. Thus, EPCR
      function appears to be important for PC activation by cancer cells. In addition,
      we detected EPCR expression in tumor cells from breast cancer patients, with an
      extremely high frequency. EPCR function may contribute to progression or
      pathogenesis of some types of cancer, and may explain the complexity of
      coagulopathy in cancer patients.

PMID- 11246561
TI  - Effect of intradermal tumor necrosis factor-alpha-induced inflammation on
      coagulation factors in dermal vessel endothelium. An in vivo study of human skin
      biopsies.
AB  - Inflammatory mediators were shown to exert procoagulant effects on cultured human
      endothelial cells (EC). In the present study the effect of intradermal
      application of tumor necrosis factor-alpha (TNF-alpha) on the expression of
      factors involved in regulation of coagulation at the EC surface, i.e. tissue
      factor (TF), thrombomodulin (TM) and tissue factor pathway inhibitor (TFPI) was
      studied in humans in vivo. The endothelial expression of these factors was
      evaluated immunohistochemically in biopsies taken after intradermal application
      of 5000 U TNF-alpha in 8 healthy volunteers. After 6 and 22 h biopsies were taken
      from the injection sites. At TNF-alpha injected sites typical inflammatory
      changes. e.g. EC upregulation of adhesion molecules and accumulation of
      leukocytes were detected. In parallel we could document EC expression of TF,
      downregulation of TM and depletion of tissue factor pathway inhibitor (TFPI) in
      inflamed areas. Early depletion of endothelial IkappaB alpha at the site of
      inflammation after application of TNF-alpha points to an activation of the NF
      kappaB pathway. Our data suggest that, as shown in in vitro experiments, TNF
      alpha activates the NF-kappaB pathway and induces specific procoagulant changes
      of EC due to expression of TF, down-regulation of TM and depletion of TFPI in
      vivo in humans. This procoagulant shift in the haemostatic balance on the cell
      surface, caused by TNF-alpha-induced inflammation, is likely to contribute to
      thrombosis associated with tissue inflammation in humans.

PMID- 11246562
TI  - Oxidative stress and increase of vascular endothelial growth factor in plasma of
      patients with peripheral arterial occlusive disease.

PMID- 11246563
TI  - Influence of the ABO blood type on the platelet function analyzer PFA-100.

PMID- 11246564
TI  - Deep vein thrombosis during varicella in a child with factor V Leiden mutation
      and familial deficiency of protein S.

PMID- 11246565
TI  - Hemostatic effects of tamoxifen in hereditary hemorrhagic telangiectasia.

PMID- 11246566
TI  - Rebuttal to circulating IL-6 levels in chronic obstructive pulmonary disease.

PMID- 11246567
TI  - Rebuttal to massive skin necrosis associated to the prothrombin gene G20210A
      mutation.

PMID- 11246568
TI  - 5th International Dead Sea Symposium on Cardiac Arrhythmias and Device Therapy.
      Dead Sea, Israel, 29 February-3 March 2000. Abstracts.

PMID- 11246570
TI  - ANAKON 99: A preview of tomorrow's Analytical Chemistry. Proceedings of a
      conference. Konstanz, Germany, April 7-10, 1999.

PMID- 11246569
TI  - Cardiostim 2000. 12th International Congress on Cardiac Electrophysiology. Nice
      Acropolis, France, 14-17 June 2000. Abstracts.

PMID- 11246571
TI  - Causal values.

PMID- 11246572
TI  - Is the jury still out on folic acid and congenital anomalies?

PMID- 11246573
TI  - The epidemiologic study of birth defects and pesticides.

PMID- 11246575
TI  - Assessment of structured socioeconomic effects on health.
AB  - Social epidemiologists study effects of variables such as education or income on
      health outcomes. Because other factors may influence both the exposure and the
      outcome, adjustments are commonly made in an effort to estimate the "independent"
      effect of exposure. The validity of common adjustment strategies when estimating
      the outcome distribution under hypothetical interventions of the exposure is
      potentially compromised by structured relations between covariates, observed and
      unobserved. These considerations of covariate structure may be particularly
      important for the study of "distal" socioeconomic factors that affect health
      through specified intermediates, therefore making standard adjustments in social
      epidemiology potentially problematic. Two related approaches have been proposed
      for defining and estimating causal effects in light of covariate structure:
      Robins' g-computation algorithm and Pearl's non-parametric structural equations.
      We review the conceptual foundation for these techniques, and provide a heuristic
      example using data from the National Longitudinal Mortality Study (NLMS) to
      demonstrate the extent to which selected causal effects (contrasts between
      hypothetical intervention regimens) are sensitive to structured relations among
      measured and unmeasured covariates, even in very simple systems.

PMID- 11246574
TI  - A case-control study of pesticides and fetal death due to congenital anomalies.
AB  - We examined the association between late fetal death due to congenital anomalies
      (73 cases, 611 controls) and maternal residential proximity to pesticide
      applications in ten California counties. A statewide database of all applications
      of restricted pesticides was linked to maternal address to determine daily
      exposure status. We examined five pesticide chemical classes. The odds ratios
      from logistic regression models, adjusted for maternal age and county, showed a
      consistent pattern with respect to timing of exposure; the largest risks for
      fetal death due to congenital anomalies were from pesticide exposure during the
      3rd-8th weeks of pregnancy. For exposure either in the square mile of the
      maternal residence or in one of the adjacent 8 square miles, odds ratios ranged
      from 1.4 (95% confidence interval = 0.8-2.4) for phosphates, carbamates, and
      endocrine disruptors to 2.2 (95% confidence interval = 1.3-3.9) for halogenated
      hydrocarbons. Similar odds ratios were observed when a more restrictive
      definition of nonexposure (not exposed to any of the five pesticide classes
      during the 3rd-8th weeks of pregnancy) was used. The odds ratios for all
      pesticide classes increased when exposure occurred within the same square mile of
      maternal residence.

PMID- 11246576
TI  - Low serum cholesterol concentration and risk of suicide.
AB  - Recent reports have suggested a link between low serum total cholesterol and risk
      of death from suicide. We examined this association using participants in the
      1970-1972 Nutrition Canada Survey. We determined the mortality experience of
      Nutrition Canada Survey participants older than 11 years of age at baseline
      through 1993 by way of record linkage to the Canadian National Mortality
      Database. The relation between low serum total cholesterol and mortality from
      suicide was assessed using a stratified analysis (N = 11,554). There were 27
      deaths due to suicide. Adjusting for age and sex, we found that those in the
      lowest quartile of serum total cholesterol concentration (<4.27 mmol/liter) had
      more than six times the risk of committing suicide (rate ratio = 6.39; 95%
      confidence interval = 1.27-32.1) as did subjects in the highest quartile (>5.77
      mmol/liter). Increased rate ratios of 2.95 and 1.94 were observed for the second
      and third quartiles, respectively. The effect persisted after the exclusion from
      the analysis of the first 5 years of follow-up and after the removal of those who
      were unemployed or who had been treated for depression. These data indicate that
      low serum total cholesterol level is associated with an increased risk of
      suicide.

PMID- 11246577
TI  - Body mass index and mortality: a twelve-year prospective study in Korea.
AB  - The relation between body mass index (kg/m2) and noncoronary mortality is not
      well established. To study this relation, a population with low coronary
      mortality may be especially useful. We conducted a 12-year follow-up study of
      235,398 Korean men 40-64 years of age. Study subjects had undergone health
      examinations in 1986 (baseline) and 1990. We excluded subjects with substantial
      weight loss during this period. There were 13,387 deaths, including 600 deaths
      from coronary events, between 1990 and 1998. We estimated the relation of body
      mass index to the risk of death after adjusting for common risk factors. There
      was a positive relation between body mass index and coronary mortality, but this
      relation was attenuated after serum total cholesterol, blood pressure, and
      fasting serum glucose were taken into account. A J-shaped relation with
      cerebrovascular mortality was also attenuated after adjustment. Even after this
      adjustment and exclusion of early deaths between 1990 and 1994, the relation of
      body mass index to all-cause (U-shaped), cancer (J-shaped), and noncancer
      noncoronary noncerebrovascular (inverse J-shaped) mortality remained. Both high
      and low body mass index were related to increased mortality among these Korean
      men.

PMID- 11246578
TI  - Work-related stress and early atherosclerosis.
AB  - The purpose of this study was to examine the link between work-related stress and
      early atherosclerosis as measured by common carotid artery intima-media thickness
      and focal lesions in the common carotid artery and bifurcation. Four hundred
      sixty-seven members of an occupational cohort (total N = 573) were examined via
      questionnaires and B-mode ultrasound. We used multiple linear and logistic models
      to regress lesion risk and intima-media thickness on work-related stress scores
      from a questionnaire administered at an 18-month follow-up examination. In an age
      adjusted model, the prevalence of carotid lesions among men scoring in the
      highest stress quintile was 36% compared with 21% among men in the lowest
      quintile. We also observed an increase in intima-media thickness in the highest
      quintile relative to the lowest (difference = 0.048 +/- 0.025 mm) among men.
      Among women, stress was not related to the prevalence of lesions or intima-media
      thickness. These findings suggest that men with greater work-related stress are
      at increased risk for atherosclerotic disease. Women in this age group may be
      protected from such effects, or current work-place questionnaires may not
      accurately assess stress in women.

PMID- 11246579
TI  - Referent selection in case-crossover analyses of acute health effects of air
      pollution.
AB  - The case-crossover design was proposed for the study of a transient effect of an
      intermittent exposure on the subsequent occurrence of a rare acute-onset disease.
      This design can be an alternative to Poisson time series regression for studying
      the health effects of fine particulate matter air pollution. Characteristics of
      time-series of particulate matter, including long-term time trends, seasonal
      trends, and short-term autocorrelations, require that referent selection in the
      case-crossover design be considered carefully and adapted to minimize bias. We
      performed simulations to evaluate the bias associated with various referent
      selection strategies for a proposed case-crossover study of associations between
      particulate matter and primary cardiac arrest. Some a priori reasonable
      strategies were associated with a relative bias as large as 10%, but for most
      strategies the relative bias was less than 2% with confidence interval coverage
      within 1% of the nominal level. We show that referent selection for case
      crossover designs raises the same issues as selection of smoothing method for
      time series analyses. In addition, conditional logistic regression analysis is
      not strictly valid for some case-crossover designs, introducing further bias.

PMID- 11246580
TI  - A case-crossover analysis of particulate matter air pollution and out-of-hospital
      primary cardiac arrest.
AB  - Numerous epidemiologic studies have reported increases in the daily incidence of
      cardiovascular mortality and morbidity associated with increases in daily levels
      of particulate matter air pollution. We studied the association between the
      incidence of primary cardiac arrest and two daily measures of particulate matter
      using a case-crossover study of 362 cases of out-of-hospital cardiac arrest. All
      cases were attended by paramedics and had no history of clinically recognized
      heart disease or life-threatening comorbidities. We compared particulate matter
      levels at index times with particulate matter levels from referent days matched
      on day of week within strata defined by month and year. The estimated relative
      risk at a lag of 1 day for an interquartile range (IQR) change in nephelometry
      (0.51 x 10(-1) km(-1)) was 0.893 (95% CI = 0.779-1.024). The estimated relative
      risk at a lag of 1 day for an IQR change in PM10 (19.3 microg m(-3)) was 0.868
      (95% CI = 0.744-1.012). Other lag periods gave similar results. We did not find
      evidence of confounding by carbon monoxide or sulfur dioxide. Analysis of effect
      modification by individual-level variables did not reveal any susceptible
      subgroups. These findings do no support an association between particulate matter
      and increased risk of primary cardiac arrest among persons without clinically
      recognized heart disease. The null results of this study may result from several
      factors, including the highly selected nature of this case series and the
      relatively low particulate matter levels in the Seattle metropolitan area.

PMID- 11246581
TI  - Air pollution and exacerbation of asthma in African-American children in Los
      Angeles.
AB  - Significant increases in asthma morbidity and mortality in the United States have
      occurred since the 1970s, particularly among African-Americans. Exposure to
      various environmental factors, including air pollutants and allergens, has been
      suggested as a partial explanation of these trends. To examine relations between
      several air pollutants and asthma exacerbation in African-Americans, we recruited
      a panel of 138 children in central Los Angeles. We recorded daily data on
      respiratory symptoms and medication use for 13 weeks and examined these data in
      conjunction with data on ozone (O3) nitrogen dioxide (NO2), particulate matter
      (PM10 and PM2.5), meteorological variables, pollens, and molds. Using generalized
      estimating equations, we found associations between respiratory symptom
      occurrence and several environmental factors. For example, new episodes of cough
      were associated with exposure to PM10 (OR = 1.25; 95% CI = 1.12-1.39;
      interquartile range [IQR] = 17 microg/m3, 24-hour average), PM2.5 (OR = 1.10; 95%
      CI = 1.03-1.18; IQR = 30 microg/m3, 12-hour average), NO2, and the molds
      Cladosporium and Alternaria, but not with exposure to O3 or pollen. The factors
      PM10 and O3 were associated with the use of extra asthma medication. For this
      population several bioaerosols and air pollutants had effects that may be
      clinically significant.

PMID- 11246582
TI  - Alcohol as a gastric disinfectant? The complex relationship between alcohol
      consumption and current Helicobacter pylori infection.
AB  - Alcoholic beverages have antimicrobial effects against Helicobacter pylori in
      vitro. To elucidate the relation between alcohol consumption and current
      infection with H. pylori in vivo, we carried out a pooled analysis of three
      recent studies from Southern Germany, comprising 1410 adults age 15 to 69.
      Detailed information on consumption of various alcoholic beverages was collected
      through standardized questionnaires. Helicobacter pylori infection was measured
      by 15C-urea breath test. Overall, prevalence of current H. pylori infection was
      lower among subjects who consumed alcohol (34.9%) than among nondrinkers (38.0%).
      The adjusted odds ratio was 0.79, with a 95% confidence interval of 0.58-1.08.
      Furthermore, alcohol consumption showed a strong inverse relation to the result
      of the 13C-urea breath test, a semiquantitative measure of the bacterial load,
      among infected subjects. The inverse association between alcohol consumption and
      H. pylori infection was not monotonic, however. Odds of infection were lowest at
      moderate levels of alcohol consumption and increased at higher levels of alcohol
      consumption, regardless of the type of alcoholic beverages consumed. These
      results support the hypothesis that moderate alcohol consumption may favor
      suppression and eventual elimination of H. pylori infection. At higher levels of
      alcohol consumption, the antimicrobial effects of alcoholic beverages may be
      opposed by adverse systemic effects of drinking, such as adverse effects on the
      immune defense.

PMID- 11246583
TI  - Family history of coronary heart disease, a strong risk factor for myocardial
      infarction interacting with other cardiovascular risk factors: results from the
      Stockholm Heart Epidemiology Program (SHEEP).
AB  - We explored the relation between family history of coronary heart disease and the
      risk of myocardial infarction in a case-control study of subjects, 45 to 70 years
      of age, living in Stockholm, Sweden. Our cases comprised 1091 male and 531 female
      first-time acute myocardial infarction patients who had survived at least 28 days
      after their infarction. Referents were randomly selected from the population from
      which the cases were derived. The adjusted odds ratio (OR) of myocardial
      infarction was 2.0 (95% confidence interval [CI] = 1.6-2.6) for men reporting >
      or = 1 affected parent or sibling, compared with men with no family history of
      coronary heart disease, and 3.4 (95% CI = 2.1-5.9) for those reporting > or = 2
      affected parents or siblings. The corresponding OR for women were 2.1 (95% CI =
      1.5-3.0) and 4.4 (95% CI = 2.4-8.1). We found evidence for synergistic
      interactions in women exposed to family history of coronary heart disease in
      combination with current smoking and with a high quotient between low-density
      lipoprotein and high-density lipoprotein cholesterol (>4.0), respectively, which
      yielded adjusted synergy index scores of 2.9 (95% CI = 1.2-7.2) and 3.8 (95% CI =
      1.5-9.7), respectively. Similarly, in men we found evidence for interaction for
      the co-exposure of family history of coronary heart disease and diabetes
      mellitus. Our study shows that family history of coronary heart disease is not
      only a strong risk factor for myocardial infarction in both sexes, but that its
      effect is synergistic with other cardiovascular risk factors as well.

PMID- 11246584
TI  - A population-based case-referent study of myocardial infarction and occupational
      exposure to motor exhaust, other combustion products, organic solvents, lead, and
      dynamite. Stockholm Heart Epidemiology Program (SHEEP) Study Group.
AB  - This case-referent study investigated the risk of myocardial infarction from
      occupational exposure to motor exhaust, other combustion products, organic
      solvents, lead, and dynamite. We identified first-time, nonfatal myocardial
      infarctions among men and women 45-70 years of age in Stockholm County from 1992
      through 1994. We selected referent subjects from the population to match the
      demographic characteristics of the cases. A lifetime history of occupations was
      obtained by questionnaire. The response rate was 81% for the cases and 74% for
      the referents, with 1,335 cases and 1,658 referents included in the study. An
      occupational hygienist assessed occupational exposures, coding the intensity and
      probability of exposure for each subject. We adjusted relative risk estimates for
      tobacco smoking, alcohol drinking, hypertension, diabetes mellitus, overweight,
      and physical inactivity at leisure time. The relative risk of myocardial
      infarction was 2.11 (95% confidence interval = 1.23-3.60) among those who were
      highly exposed and 1.42 (95% confidence interval = 1.05-1.92) among those who
      were intermediately exposed to combustion products from organic material. We
      observed an exposure-response pattern, in terms of both maximum exposure
      intensity and cumulative dose. Exposure to dynamite and organic solvents was
      possibly associated with an increased risk. The other exposures were not
      consistently associated with myocardial infarction.

PMID- 11246585
TI  - The risk of cataract among users of inhaled steroids.
AB  - Prolonged exposure to inhaled corticosteroids among adults over 49 years old has
      been reported to increase cataract risk. Small-scale studies of inhaled steroid
      users suggest that no increased risk for children and young adults exists. To
      describe cataract risk among people with asthma who use inhaled corticosteroids
      relative to patients with asthma with no history of corticosteroid use, we
      conducted a retrospective observational cohort study of patients identified from
      the United Kingdom-based General Practice Database with a nested case-control
      analysis. Relative to patients who do not use corticosteroids, all inhaled
      corticosteroid users were at a marginally increased risk of cataract (RR = 1.3).
      Among individuals 40 years of age or older, the risk ratio increased with use of
      increasing numbers of inhaled corticosteroid prescriptions after controlling for
      diabetes mellitus, hypertension, and smoking history. This trend was not evident
      in those under age 40.

PMID- 11246586
TI  - The association of indicators of fetal growth with visual acuity and hearing
      among conscripts.
AB  - Impaired fetal growth is associated with increased susceptibility to several
      chronic diseases. We studied the association between birth weight, indicators of
      disproportional fetal growth, and impaired visual acuity and hearing in 4,300
      conscripts from a well-defined region in Denmark from August 1, 1993, to July 31,
      1994. From the standard health examination for conscripts, we obtained data on
      sight based on the Snellen's chart and data on hearing acuity based on
      audiometry. By means of record linkage, we obtained data on outcomes for the
      conscripts at birth from the Medical Birth Registry. From this registry, we have
      data on birth weight, gestational age, and birth length that were recorded from
      existing computerized registers based on the records of midwives. A birth weight
      of less than 3,000 gm and a body mass index at birth of less than 3.4 were
      associated with reduced visual acuity and impaired hearing. The results could be
      due to fetal brain programming or due to confounding, by early birth trauma or
      other factors.

PMID- 11246587
TI  - Alcohol consumption in relation to 20-year  COPD mortality and pulmonary function
      in middle-aged men from three European countries.
AB  - Alcohol consumption shows a U-shaped relation with all-cause and cardiovascular
      mortality. To determine whether a similar relation exists between alcohol and
      chronic obstructive pulmonary disease mortality, we analyzed data on alcohol
      consumption in 1970 and 20-year mortality from chronic obstructive pulmonary
      disease among 2,953 middle-aged men from Finland, Italy, and the Netherlands. We
      also studied alcohol consumption in relation to pulmonary function (FEV1 or
      FEV0.75) at baseline. We used regression models adjusted for age, height (for
      pulmonary function only), body mass index, smoking habits, energy intake, and
      country. A smoothed spline-plot showed a U-shaped relation between alcohol and
      chronic obstructive pulmonary disease mortality. Compared with non-drinkers and
      occasional drinkers, the relative risk of chronic obstructive pulmonary disease
      mortality was 0.60 (95% CI = 0.33-1.09) in light drinkers (> 1 drink per week, <
      or = 3 drinks per day) and 1.25 (95% CI = 0.47-3.31) in moderate-to-heavy
      drinkers. Pulmonary function was lower in non-drinkers compared with occasional
      and light drinkers in Finland (75 ml, 95% CI = -2 to 151) and the Netherlands (93
      ml, 95% CI = 0-186) and lower in very heavy (> 12 drinks per day) compared with
      moderate-to-heavy drinkers in Italy (99 ml, 95% CI = 9-189). In conclusion, we
      observed a U-shaped curve between alcohol consumption and 20-year chronic
      obstructive pulmonary disease mortality in middle-aged men that was supported by
      cross-sectional data on alcohol and pulmonary function.

PMID- 11246588
TI  - A psychometric experiment in causal inference to estimate evidential weights used
      by epidemiologists.
AB  - A psychometric experiment in causal inference was performed on 159 Australian and
      New Zealand epidemiologists. Subjects each decided whether to attribute causality
      to 12 summaries of evidence concerning a disease and a chemical exposure. The
      1,748 unique summaries embodied predetermined distributions of 19 characteristics
      generated by computerized evidence simulation. Effects of characteristics of
      evidence on causal attribution were estimated from logistic regression, and
      interactions were identified from a regression tree analysis. Factors with the
      strongest influence on the odds of causal attribution were statistical
      significance (odds ratio = 4.5 if 0.001 < or = P < 0.05 and 7.2 if P < 0.001, vs
      P > or = 0.05); refutation of alternative explanations (odds ratio = 8.1 for no
      known confounder vs none adjusted); strength of association (odds ratio = 2.0 if
      1.5 < relative risk < or = 2.0 and 3.6 if relative risk > 2.0, vs relative risk <
      or = 1.5); and adjunct information concerning biological, factual, and
      theoretical coherence. The refutation of confounding reduced the cutpoint in the
      regression tree for decision-making based on strength of association. The effect
      of the number of supportive studies reached saturation after it exceeded 12
      studies. There was evidence of flawed logic in the responses concerning
      specificity of effects of exposure and a tendency to discount evidence if the P
      value was a "near miss" (0.050 < P < 0.065). Evidential weights based on
      regression coefficients for causal criteria can be applied to actual scientific
      evidence.

PMID- 11246589
TI  - Is there a common etiology for the rising incidence of and decreasing survival
      with adenocarcinoma of the lung?
AB  - We studied possible explanations for the deteriorating survival for
      adenocarcinoma of the lung between 1975 and 1994 in relation with trends in
      incidence. The proportion of adenocarcinoma among men has been increasing since
      1975 and for those born after 1920, while survival has decreased since 1975 and
      for those born since 1930. Among women, both the proportion of adenocarcinoma and
      survival have remained more or less constant. The rising incidence and the
      decreasing survival may both be related to changes in tobacco use, the increased
      use of low-tar filter cigarettes since the 1960s being the most likely candidate.

PMID- 11246590
TI  - A comparison of the National Death Index and Social Security Administration
      databases to ascertain vital status.
AB  - We compared vital status follow-up by the National Death Index and the Social
      Security Administration for a cohort of breast cancer patients. Only the National
      Death Index allowed follow-up for subjects with an unknown Social Security
      number. All of the deaths identified by the Social Security Administration were
      reported by the National Death Index. No subject reported to be alive by the
      Social Security Administration matched a National Death Index record. Subjects
      with inaccurate identifying information were more effectively followed up by the
      National Death Index. The National Death Index more accurately reported dates of
      death.

PMID- 11246591
TI  - Do we need another randomized controlled trial of folic acid alone?
AB  - As a public health strategy to help prevent neural tube defect-affected
      pregnancies, enriched flour and pasta in the United States and Canada are being
      fortified with folic acid, and women are being advised to take supplementary
      folic acid around the time of pregnancy to ensure an adequate intake. But in
      spite of the recently published results of a public health campaign in China, the
      burden of proof that folic acid alone is responsible for a decreased risk of
      these birth defects rests on the results of a randomized controlled trial
      conducted by the Medical Research Council of the United Kingdom. Supporting
      evidence comes primarily from studies that have shown a protective effect of
      multivitamins containing folic acid as one of many nutrients. Based on a striking
      and potentially hazardous type of non-compliance observed in an earlier study in
      which a participant took multiple vitamin doses simultaneously and a suggestion
      of similar incidents in the Medical Research Council study, we conclude that a
      further randomized controlled trial of the protective effect of folic acid alone
      may be necessary.

PMID- 11246592
TI  - The role of epidemiology in understanding the health effects of Helicobacter
      pylori.
AB  - Helicobacter pylori infects one-half or more of the world population and causes
      chronic gastritis, peptic ulcer, and probably gastric cancer as well. The public
      health impact of this infection is far from trivial. Chronic gastritis and peptic
      ulcer disease are common across populations. Gastric cancer rates have declined
      during this century, but this cancer remains second among causes of cancer deaths
      worldwide. Much has been learned about biological and clinical aspects of H.
      pylori, but key epidemiologic questions have not been answered. How infection
      results in diverse diseases, the precise modes of transmission, and a
      comprehensive solution to H. pylori as a public-health problem remain elusive. In
      this paper, we highlight methodologic challenges and outline an agenda for future
      research. Challenges include improving validation of detection methods and
      considering the limitations of these methods when interpreting epidemiologic
      data. The role of cofactors in H. pylori-induced diseases requires extensive
      exploration. Many intriguing areas of H. pylori research require the skills of
      epidemiologists. The discovery of an infectious etiology of common chronic
      diseases presents a promising opportunity for improving public health.

PMID- 11246593
TI  - Role of organochlorine compounds in the etiology of pancreatic cancer: a proposal
      to develop methodological standards.
AB  - Studies on the possible role of organochlorine compounds in the etiology of
      pancreatic and other cancers face a set of methodologic and logistic issues that
      stem from the lipophilic nature of most organochlorines, and from the fact that
      tumor-induced lipid mobilization, weight loss, and metabolic changes can be
      profound before diagnosis. The question thus arises: do the xenobiotic
      concentrations in blood and adipose tissue result, in part, from such
      pathophysiologic changes? To assess and control potential selection and
      information biases, a flexible framework is warranted. It could be based on
      indicators such as time elapsed between the first symptom of cancer and blood or
      fat sample extraction; signs, symptoms and clinical status at the time of
      extraction; cholesterol and triglycerides levels; other laboratory findings;
      tumor stage at diagnosis; diagnostic procedures; treatment type and timing;
      clinical complications; and survival. Before adopting qualitative criteria and
      quantitative standards, their impact upon causal estimators should be assessed
      empirically.

PMID- 11246594
TI  - Update on World Health Organization's initiative to assess environmental burden
      of disease.

PMID- 11246595
TI  - Use of different hospital data bases in the estimation of the relation between
      air pollution and chronic obstructive pulmonary disease.

PMID- 11246596
TI  - Second primary cancers after in situ and invasive cervical cancer.

PMID- 11246597
TI  - Population factors not addressed in cohort study.

PMID- 11246598
TI  - Drospirenone--a new progestogen with antimineralocorticoid activity, resembling
      natural progesterone.
AB  - In the second half of a normal menstrual cycle, progesterone levels rise.
      Progesterone binds to its specific receptor, but also to the mineralocorticoid
      receptor; thus progesterone acts as a mineralocorticoid antagonist. For this
      reason, natriuresis is slightly enhanced in the luteal phase, and, as a
      reflection of the negative sodium balance, plasma renin and aldosterone rise by
      20-50%. This rise is of a compensatory nature, and prevents further sodium
      losses. All conventional synthetic progestogens, whether they are derivatives of
      17alpha-hydroxyprogesterone or 19-nortestosterone, lack the antimineralocorticoid
      effect of natural progesterone. Ethinylestradiol, as the estrogenic component of
      combined oral contraceptives, is a sodium-retaining drug. This effect is mainly
      due to a significant increase of the hepatic synthesis of renin substrate
      (angiotensinogen). Even with low-dose oral contraceptives, systolic and diastolic
      blood pressure may be raised in susceptible individuals. Drospirenone is a new
      progestogen, derived from 17alpha-spirolactone, and the relationship between its
      progestogenic and its antimineralocorticoid potency is almost identical to that
      of natural progesterone. In an early preclinical study in 12 normal young women,
      it was found that the oral administration of 2 mg drospirenone for 6 days led to
      a cumulative sodium loss of 84 mmol and a significant rise in plasma renin and
      aldosterone, compared with placebo. In a second experiment, it was found that 2
      mg drospirenone given from cycle days 5 to 25 to six regularly menstruating women
      suppressed ovulation and led to a slight natriuresis without a change in blood
      pressure, while renin and aldosterone levels slightly increased. The natriuresis
      and the increase in renin and aldosterone levels did not occur in six other women
      who received 1 mg cyproterone acetate (a progestogen with antiandrogenic
      properties), instead of drospirenone. Consequently, an oral contraceptive was
      designed containing 30 microg ethinylestradiol and 3 mg drospirenone (Yasmin,
      Schering AG, Berlin, Germany) in the hope of developing a contraceptive that
      might prevent the sodium retention brought about by the effect of
      ethinylestradiol. In a 6-month study involving 20 regularly menstruating women,
      it was shown that the addition of drospirenone to ethinylestradiol did indeed
      prevent the small rise in body weight and blood pressure observed in some women
      taking a conventional oral contraceptive. In all studies conducted so far with
      Yasmin, cycle control and tolerability have been found to be good. In conclusion,
      Yasmin may become an especially well-tolerated combined oral contraceptive, due
      to the striking similarity between its progestogenic component drospirenone and
      progesterone.

PMID- 11246599
TI  - The contraceptive profile of a new oral contraceptive with antimineralocorticoid
      and antiandrogenic effects.
AB  - Yasmin (Schering AG, Berlin, Germany), a new oral contraceptive containing 30
      microg ethinylestradiol combined with 3 mg drospirenone, effectively inhibits
      ovulation, as demonstrated by measurement of plasma hormone levels (follicle
      stimulating hormone, luteinizing hormone, estradiol and progesterone), and
      echographic evaluation of follicular ripening. Like other low-dose oral
      contraceptives, the combination of ethinylestradiol and drospirenone markedly
      limits cervical function, spinnbarkeit and degree of crystallization, resulting
      in a hostile environment for sperm penetration. Two large, randomized,
      multicenter, open-label clinical studies have compared the contraceptive efficacy
      of ethinylestradiol/drospirenone with that of Marvelon, a well-established
      contraceptive containing 30 microg ethinylestradiol plus 150 microg desogestrel.
      Both preparations provided effective contraception and good cycle control. There
      were no negative effects on hemostatic parameters, lipids and carbohydrate
      metabolism. However, in both studies, ethinylestradiol/drospirenone had a more
      favorable effect on body weight than ethinylestradiol/desogestrel, with mean body
      weight remaining lower in the ethinylestradiol/ drospirenone group, the
      difference between the two preparations being statistically significant. Pre
      existing acne and seborrhea were improved by ethinylestradiol/ drospirenone and
      blood pressure was essentially unchanged. These studies show that
      ethinylestradiol/drospirenone provides effective oral contraception, excellent
      cycle control and good tolerability, with effects on body weight and skin
      condition that are likely to confer a significant beneficial effect on
      compliance, especially in women with a tendency to gain weight under oral
      contraceptives due to water retention.

PMID- 11246600
TI  - The acceptability of a novel oral contraceptive containing drospirenone and its
      effect on well-being.
AB  - Low-dose combined oral contraceptives are generally well tolerated and represent
      an excellent reversible form of contraception that is suitable for most women.
      Certain aspects of the clinical profile of combined oral contraceptives, such as
      intermenstrual bleeding and a tendency to weight gain, are, however, known to
      have an adverse effect on compliance, which may in a few women lead to
      contraceptive failure or pill discontinuation. Conversely, factors that have a
      positive effect, such as relief from the symptoms of premenstrual syndrome, can
      enhance compliance. An oral contraceptive that minimizes the adverse and enhances
      the positive effects would, therefore, be likely to improve compliance. Recently,
      a new combined oral contraceptive containing 30 microg ethinylestradiol and 3 mg
      drospirenone (Yasmin, EE/DRSP) has been developed. The pharmacological profile of
      drospirenone is very similar to that of natural progesterone; in particular, it
      has antimineralocorticoid activity. This counteracts estrogen-mediated fluid
      retention, resulting in stable or slightly lowered body weight. In addition,
      drospirenone has antiandrogenic activity and therefore a positive effect on skin
      conditions. Present data also indicate that EE/DRSP has a favorable effect on the
      symptoms of premenstrual syndrome. In order to evaluate whether the positive
      effects of drospirenone on body weight, skin and the symptoms of premenstrual
      syndrome are also observed on well-being, a survey was carried out. This asked
      women who had been involved in two major clinical trials how they felt after
      these trials had ended, in comparison with the study periods when they were
      taking EE/DRSP or a combined oral contraceptive containing 30 microg
      ethinylestradiol/150 microg desogestrel (Marvelon, EE/DSG). The returned
      questionnaires demonstrated that, with respect to their disposition before and
      during menses, women who had taken EE/DRSP felt worse after the trial had ended
      and they had returned to taking a conventional preparation. This was also evident
      on the basis of their body weights and the condition of their skin and hair.
      These results from clinical trials with EE/DRSP indicate that it is a well
      tolerated combined oral contraceptive that has a positive effect on body weight,
      skin and the symptoms of premenstrual syndrome. Overall, the combination of 30
      microg ethinylestradiol/3 mg drospirenone appears to improve specific aspects
      associated with feelings of well-being, which may result in better compliance.

PMID- 11246601
TI  - Yasmin--a new oral contraceptive, a new progestogen: the reasons why.
AB  - There are over 60 million women using oral contraceptives worldwide, yet there
      are wide differences between different countries in the use of oral
      contraceptives and, in particular, in discontinuation rates. Large differences in
      rates of sterilization and of teenage pregnancy also highlight the fact that
      there are considerable geographical differences in oral contraceptive use. There
      are probably many reasons for these differences, including lack of information
      about the non-contraceptive benefits of oral contraceptives, differences in
      national health-care policies and systems, women's fears about side-effects and
      possible side-effects, and social, cultural and religious differences. In order
      to provide better choices of oral contraceptives, there is a need to consider new
      oral contraceptives, such as Yasmin (Schering AG, Berlin, Germany), which is
      formulated with ethinylestradiol and drospirenone, a progestogen which is
      pharmacologically very similar to progesterone. Unlike other progestogens,
      drospirenone is associated with weight stability or slight weight loss due to
      less water retention, one of the factors which is known to be of great importance
      in supporting compliance with oral contraceptives. Drospirenone also shares with
      some other progestogens the capacity to improve acne and seborrhea in
      hyperandrogenic women. Taken together, these properties make it likely that the
      combination of ethinylestradiol with drospirenone will contribute to improving
      oral contraceptive compliance, thereby maximizing the overall benefits of oral
      contraception.

PMID- 11246602
TI  - The pharmacokinetics and pharmacodynamics of Implanon, a single-rod etonogestrel
      contraceptive implant.
AB  - This paper reviews pharmacokinetic and pharmacodynamic studies with Implanon,
      which provides serum etonogestrel levels sufficient to inhibit ovulation within 8
      h of insertion. After a peak of 813 pg/ml at 4 days, levels reach steady state
      (200 pg/ml) after 4-6 months and remain sufficient to prevent ovulation for 3
      years. Variability is lower than with Norplant. Etonogestrel levels are similar
      in most ethnic groups, but 40% higher in women weighing < 50 kg. After implant
      removal, etonogestrel is not detectable within 1 week. Implanon inhibits
      ovulation by preventing the mid-cycle luteinizing hormone peak. Although it
      initially suppresses follicular development and estradiol production, ovarian
      activity slowly increases after 6 months, and follicle stimulating hormone and
      estradiol levels are almost normal. Endogenous progesterone levels remain in the
      subovulatory range for > 3 years in most subjects. In ovarian ultrasound studies,
      ovulation occurred in < 5% of users after 30 months of use. Ovulation was
      observed in most women within 3-4 weeks of implant removal. The pharmacokinetics
      and pharmacodynamics of Implanon indicate that it has high contraceptive
      efficacy, as reflected in a zero pregnancy rate over 5,629 woman-years of use.
      Its excellent reliability, ease of use, and reversibility make Implanon a
      valuable addition to current contraceptives.

PMID- 11246603
TI  - Implantable contraception.
AB  - This article reviews the advantages and disadvantages of progestogen-only
      contraceptive implants in light of the development of Implanon, a new, single
      rod, etonogestrel-releasing system. Implants rapidly produce serum progestogen
      levels sufficient to ensure contraception for 1-5 years. The steady release
      ofprogestogen avoids the peaks and troughs associated with oral contraceptives,
      the profound ovarian suppression observed with depot injections and the need for
      user compliance. Implants have few serious complications. Ectopic pregnancy rates
      are low, and follicular hypertrophy is generally self-limiting. The principal
      acceptability limitation to both users and providers of Norplant is insertion and
      removal. Implanon is easy to insert and remove with minimal complications and
      pain. The main adverse event causing discontinuation of implants is a change in
      bleeding pattern. However, with good counselling, this is well tolerated by most
      women. Implants thus provide an effective, safe, economical and convenient
      alternative to oral, injectable or intrauterine contraceptives. Implanon is an
      extremely effective single-rod implant with a Pearl index of 0. It employs a new
      polymer and a less androgenic progestogen. These features provide easier
      insertion and removal for both users and clinicians, a more stable release rate
      and potentially fewer adverse androgenic effects compared with existing
      formulations.

PMID- 11246604
TI  - Clinical profile of Implanon: a single-rod etonogestrel contraceptive implant.
AB  - This 3-year study investigating the contraceptive efficacy and tolerability of
      Implanon in 635 volunteers demonstrates that it was well tolerated and had
      excellent, reversible, contraceptive efficacy. No pregnancies (Pearl index, 0;
      95% CI 0.0-0.2) occurred during 1,200 woman-years of exposure. Irregular
      bleeding, mainly frequent and prolonged, was the primary reason for
      discontinuation (19.0%). Infrequent bleeding (29-51%) was the most common
      bleeding disturbance. Adverse events, other than bleeding irregularities, were
      generally mild to moderate in intensity and resulted in 9.3% of discontinuations.
      Over 85% of women with dysmenorrhea at baseline noted an improvement at the end
      of treatment, while 4% reported new or worsened symptoms. The most commonly
      reported non-bleeding adverse events were breast pain (16%), acne (12.6%),
      vaginitis (12%) and pharyngitis (10.5%). However, acne present at enrolment
      improved or disappeared during treatment in 59% of women. Less than 5% of women
      experienced implant site symptoms after insertion or removal, mainly mild pain of
      short duration. Average insertion and removal times were 2.2 and 5.4 min,
      respectively. In most women, menses returned to normal within 3 months of implant
      removal. Of those using no contraceptive method, 13.8% became pregnant within 90
      days. Implanon represents a highly effective contraceptive option for women.

PMID- 11246605
TI  - Insertion and removal of Implanon: practical considerations.
AB  - Implanon, a novel contraceptive implant containing the progestogen, etonogestrel
      (68 mg), provides highly effective, well-tolerated contraception for up to 3
      years. Its single-rod design, semi-rigid polymer base and convenient pre-loaded
      presentation mean that Implanon has potential insertion and removal advantages
      over the six-capsule Norplant implant. Insertion of Implanon is simple: the
      applicator needle is positioned subdermally and the cannula is withdrawn, leaving
      the implant rod in place. Implanon is removed using the 'pop out' technique,
      involving a 2-mm incision. A meta-analysis of data from seven open-label,
      randomized studies in 1,378 women compared the ease of insertion and removal of
      the Implanon and Norplant implants and the frequency of associated complications.
      It was approximately four times quicker to insert and remove Implanon than
      Norplant (mean insertion times 1.1 vs. 4.3 min, respectively; mean removal times
      2.6 vs.10.2 min, respectively). Insertion complications were very rare with both
      Implanon (0.3%) and Norplant (0.0%). However, Implanon was associated with a
      significantly lower frequency of removal complications (0.2 vs. 4.8% with
      Norplant; p < 0.001). Implant site abnormalities were uncommon. The simplicity of
      the insertion and removal procedures with Implanon may have significant
      implications for contraceptive implant training programs and user counselling.

PMID- 11246606
TI  - A swollen leg unmasks longstanding SLE.
AB  - We report a case of long-standing SLE which presented with symptomatic muscle
      vasculitis on a background of photosensitivity, arthralgia and myalgia. The
      diagnosis was complicated by cardiomyopathy, nephrotic syndrome and diabetes. We
      highlight the benefits of aggressive treatment in severe disease and the
      importance of recognising and treating comorbidity especially ih relation to
      atherosclerosis.

PMID- 11246607
TI  - Efficacy and tolerability of a low microparticle diet in a double blind,
      randomized, pilot study in Crohn's disease.
AB  - BACKGROUND: Ultrafine and fine particles are potent adjuvants in antigen-mediated
      immune responses, and cause inflammation in susceptible individuals. Following
      recent findings that microparticles accumulate in the phagocytes of intestinal
      lymphoid aggregates, this study is the first investigation of whether their
      reduction in the diet improves the symptoms of Crohn's disease. METHODS: In a
      double blind study, 20 patients with active corticosteroid-treated ileal or ileo
      colonic Crohn's disease randomly received either a low microparticle diet (trial
      group; n = 10) or a control diet (n = 10) for 4 months. Crohn's disease activity
      index (CDAI) and corticosteroid requirements were compared. RESULTS: One patient
      in each group was withdrawn. In the trial group there was a progressive decrease
      in CDAI from entry (392 +/- 25) to month 4 (145 +/- 47) (P = 0.002 vs control
      group) and seven patients were in remission (CDAI <150). In contrast, the control
      group had returned to baseline levels (302 +/- 28 on entry and 295 +/- 25 at
      month 4), with none in remission. Corticosteroid intake was reduced more in the
      trial group although this did not reach significance. CONCLUSIONS: A low
      microparticle diet may be effective in the management of ileal Crohn's disease
      and could explain the efficacy of elemental diets, which similarly are low in
      microparticles.

PMID- 11246608
TI  - Alterations in intestinal microflora, faecal bile acids and short chain fatty
      acids in dextran sulphate sodium-induced experimental acute colitis in rats.
AB  - BACKGROUND: The physiological effects on faecal bile acids and short chain fatty
      acids (SCFAs) or intestinal microflora in dextran sulphate sodium (DSS)-induced
      colitis remain unknown and are an area of interest DESIGN ALTERATIONS: of these
      parameters in DSS-induced colitis in rats were evaluated. METHODS: Male Sprague
      Dawley rats (n = 10) were given a 3% DSS aqueous solution orally for 7 days. The
      concentrations of bile acids and SCFAs in the faeces were measured using gas
      chromatography and high-performance liquid chromatography. Intestinal microflora,
      especially anaerobes, were investigated by microbiological methods. RESULTS: On
      day 7, the concentrations of lithocholic acid and alpha-muricholic acid were
      significantly decreased and that of cholic acid was significantly increased.
      There was a strong correlation between the concentration of cholic acid and the
      macroscopic area of damaged tissue in the colon (R = 0.74, P < 0.05). With
      respect to SCFAs, DSS administration significantly decreased the concentrations
      of acetic acid and n-butyric acid. There was also some correlation between the
      concentration of acetic acid and macroscopic damaged area in the colon (R = 
      0.60, P = 0.07). Bacteriological studies revealed significantly decreased
      eubacteria, bifidobacteria and total anaerobes after the administration of DSS.
      In contrast, lactobacilli were significantly increased. CONCLUSIONS: With the
      progression of DSS-induced colitis, faecal bile acids, SCFAs and intestinal
      microflora were altered. It is possible that these alterations contribute in part
      to the progression of DSS-induced colitis.

PMID- 11246609
TI  - Epidemiological, clinical, and histological characteristics of intestinal
      metaplasia at the oesophagogastric junction compared to short segments of
      columnar-lined oesophagus.
AB  - OBJECTIVE: Intestinal metaplasia (IM) close to the oesophagogastric junction
      (OGJ) has become a focus of research interest against a background of the rising
      incidence of malignancies in that area. Studies have focused on the presence of
      IM in short columnar segments (0-3 cm). Recently it has been suggested that IM at
      the OGJ and IM in short columnar segments may represent different entities. The
      objective of this current study was to determine the prevalence of IM in these
      areas and to assess clinical characteristics in order to test the hypothesis that
      IM at the OGJ and IM in short columnar segments are different entities. METHODS:
      Six hundred and fifty-eight patients referred for gastroscopy, in whom a columnar
      lining of 0-3 cm was found, participated in the study. Endoscopic oesophagitis
      was graded, distances to endoscopic landmarks were measured, and biopsies
      (antrum, corpus, 'cardia', and immediately distal to the squamocolumnar junction)
      were taken. Biopsies were stained with haematoxylin & eosin, Alcian Blue (pH
      2.5), modified Giemsa for Helicobacter pylori (Hp), and immunohistochemistry in
      cases of a negative Giemsa. According to endoscopy, patients were categorized as
      having a normal OGJ (0-1 cm) or having a short columnar segment (1 -3 cm, tongues
      >1 cm). RESULTS: In this study 77.7% of patients had a normal OGJ (IM-positive
      15.1%), and 22.3% had a short columnar segment (IM-positive 29.3%). In the first
      group, IM was correlated with Hp (P = 0.003) and antral IM (P = 0.002), in the
      second IM was associated with the presence of a hiatal hernia (P < 0.001) and
      reflux oesophagitis (P = 0.023). CONCLUSION: These findings suggest that IM at
      the OGJ is not the same entity as IM in short columnar segments.

PMID- 11246610
TI  - Evolution of clinical and radiological features at diagnosis of achalasia during
      a 19-year period in central France.
AB  - OBJECTIVES: Symptoms of achalasia are often misinterpreted, resulting in delayed
      diagnosis. The aims of our study were (1) to estimate the evolution of clinical
      and radiological features of a large population of achalasic patients between two
      successive periods; and (2) to determine the influence of symptoms on diagnostic
      delay. METHODS: Between 1980 and 1998, all achalasia patients treated in our unit
      were assessed at the time of manometric diagnosis for clinical and radiological
      features. These data were compared between two successive periods (1980-1994 and
      1994-1998). Then, a correlation between the diagnostic delay, clinical and
      radiological data and symptoms was investigated. RESULTS: Three hundred and forty
      five consecutive achalasia patients were assessed (mean age at diagnosis, 56
      years; mean diagnostic delay, 5.7 years). The duration of the disease was
      correlated with the oesophageal diameter (P = 0.0001). Dysphagia, chest pain and
      heartburn were more frequent in young patients (respectively, P = 0.003, 0.0001
      and 0.001). Women had 1.7 times the risk of men for suffering of chest pain (95%
      CI, 1.1 -2.6) and 2.2 times the risk for heartburn (95% CI, 1.2-4.0). Pulmonary
      involvement was more frequent when the oesophagus was dilated (P = 0.0002), and
      3.4 times more frequent when associated with regurgitations (95% CI, 1.3-8.9).
      The oesophageal diameter was significantly smaller (38 vs 48 mm) in the last
      period, but we have not observed any significant shortening of the diagnostic
      delay. No symptoms influenced the diagnostic delay. CONCLUSIONS: Despite a
      smaller oesophageal diameter at the time of diagnosis, during the period 1994
      1998, diagnostic delay was not reduced. No clinical features associated with late
      diagnoses could be identified.

PMID- 11246611
TI  - Acid stimulates E-cadherin surface expression on gastric epithelial cells to
      stabilize barrier functions via influx of calcium.
AB  - BACKGROUND AND AIMS: E-cadherin, which is a [Ca2+]-dependent, homotypic cell-cell
      adhesion molecule, is expressed in gastrointestinal epithelial cells. Much has
      been learned about the down-regulation of E-cadherin expression in
      gastrointestinal tumours, Barrett's oesophageal dysplasia, and Crohn's disease,
      but the functions of this molecule in normal gastrointestinal mucosa are less
      known. METHODS: In this study, we investigated the relationship between E
      cadherin expression and permeability using rat cultured gastric and intestinal
      epithelial cells following a 30-min exposure to various pH solutions. We also
      investigated the participation of [Ca2+] in these events. RESULTS: E-cadherin
      expression increased under acid (pH 4) but not alkali (pH 10 or 11) exposure only
      for gastric epithelial cells. Gastric epithelial permeability was maintained only
      against acid exposure while intestinal permeability increased under both
      conditions. Transient influx of [Ca2+] was only observed for gastric epithelial
      cells just after acid exposure. CONCLUSIONS: These findings suggest that E
      cadherin expression on gastric epithelium stabilizes the epithelial barrier
      against acid, probably through influx of [Ca2+]. This event is thought to be one
      of the protective mechanisms in gastric mucosa against acid back-diffusion, which
      is one of the causes of peptic ulcer formation.

PMID- 11246612
TI  - Serum pro-collagen III peptide levels are related to lobular necrosis in
      untreated patients with chronic hepatitis C.
AB  - OBJECTIVE: Liver biopsy is mandatory for correctly grading and staging chronic
      hepatitis activity. Nevertheless, serum markers of fibrogenesis may be useful to
      help us understand the mechanisms of the fibrogenic process, to follow-up
      patients, and to establish the efficacy of therapy. In this study, our aim was to
      identify the relationships between pro-collagen III peptide (PIIIP) serum levels
      and detailed liver histology in a group of untreated patients with chronic
      hepatitis C (CHC). METHODS: We studied 147 CHC patients. Correlation analysis of
      PIIIP serum levels was performed in 109 patients, after having excluded those
      with alcohol abuse or concomitant hepatitis B virus infection. PIIIP serum levels
      were assessed using an assay that measures both Col 1-3 peptide (reflecting
      collagen synthesis) and Col 1 peptide (reflecting collagen degradation).
      Relationships of serum PIIIP with histology was carried out by evaluating grading
      and staging separately. Moreover, each component of the necro-inflammatory score
      was also taken into consideration. RESULTS: PIIIP levels were abnormal in 101
      patients (93%). Moreover, PIIIP levels were no different between patients with
      (12.1 +/- 6.3 ng/ml) or without (13 +/- 5.8 ng/ml) fibrosis. In univariate
      analysis, no relationship was observed with fibrosis (rs = 0.033, not
      significant), while PIIIP levels were significantly correlated with lobular
      necrosis only (rs = 0.295, P = 0.0020). Multivariate analysis confirmed this
      latter finding (P = 0.0150). Among biochemical parameters, PIIIP showed
      relationships with aminotransferase (AST, rS = 0.294, P = 0.0022; ALT, rs =
      0.236, P = 0.0142) and alkaline phosphatase (rs = 0.146, P = 0.0223).
      CONCLUSIONS: In patients with CHC, serum PIIIP levels reflect histological
      parameters strictly related to fibrogenesis. Therefore, PIIIP is a useful tool to
      evaluate ongoing fibrogenic activity of CHC. A complete histological score is
      needed in order to understand the relationships between biochemical markers of
      fibrogenesis and histology.

PMID- 11246613
TI  - Treatment of mild chronic hepatitis C with interferon alpha-2b: results of a
      multi-centre randomized study in 80 patients.
AB  - OBJECTIVE: The natural history of mild chronic hepatitis C is not well-known and
      the benefit of treating this form of the disease is not well-defined. We
      conducted a pilot study to answer this question. DESIGN: Mild chronic hepatitis C
      was defined by positivity for anti-HCV antibodies, detectable serum HCV RNA by
      PCR, and a Knodell score < or = 5 on a liver biopsy performed within the previous
      6 months. Eighty patients from six centres were randomized into two groups
      receiving interferon alpha-2b, 3 MU three times a week for 6 months (group 1, n =
      39) or no treatment (group 2, n = 41). Sustained response was defined by the loss
      of detectable serum HCV RNA at 6 months after therapy. RESULTS: The two groups
      were not different at entry with respect to age, sex ratio, source of infection,
      disease duration, genotype, viral load and Knodell score. One patient (group 1)
      was excluded from the study, while two patients in group 1 (5%) and seven in
      group 2 (17.1 %) did not complete the trial. A sustained response was observed in
      seven patients (18%) in group 1 versus none in group 2 (P < 0.01). The difference
      in mean Knodell score remained non-statistically significant between the two
      groups at the end of the study. Reduction or interruption of interferon was
      necessary in eight patients (24.2%). CONCLUSIONS: This first randomized
      controlled study in mild chronic hepatitis C shows a proportion of sustained
      responders to interferon alpha-2b similar to that observed in active chronic
      hepatitis C.

PMID- 11246614
TI  - Treatment with interferon-alpha2b of naive non-cirrhotic patients with chronic
      hepatitis C according to viraemia and genotype. Results of a randomized
      multicentre study. The North West Italian Hepatological Group.
AB  - OBJECTIVE: To establish whether tailoring the dosage of interferon (IFN)-alpha2b
      in non-cirrhotic naive patients with chronic hepatitis C according to hepatitis C
      virus (HCV) genotype and viraemic level improves the rate of sustained response
      (normal alanine aminotransferase values and HCV-RNA negativity 6 months after the
      end of therapy). PATIENTS: A total of 538 consecutively collected HCV-positive
      patients with non-cirrhotic chronic hepatitis who had not been previously
      treated. METHODS: Quantitative viraemia and genotype were determined in each
      patient by a core laboratory. The patients were randomized to: Group 1, 86
      patients with genotype non-1 and viraemia < 1,000,000 HCV genome equivalents/ml
      (GenEq/ml) treated with 3 Million Units (MU) IFN three times weekly (t.i.w.) for
      1 year; Group 2, 42 patients with genotype 1 and viraemia < 1,000,000 GenEq/ ml
      treated with 3 MU IFN t.i.w. for 1 year; Group 3, 46 patients with genotype 1 and
      viraemia < 1,000,000 GenEq/ ml treated with 5 MU IFN t.i.w. for 1 year; Group 4,
      85 patients with genotype non-1 and viraemia > 1,000,000 GenEq/ml treated with 3
      MU IFN t.i.w. for 1 year; Group 5, 88 patients with genotype non-1 and viraemia >
      1,000,000 GenEq/ml treated with 5 MU IFN t.i.w. for 1 year; Group 6, 94 patients
      with genotype 1 and viraemia > 1,000,000 GenEq/ml treated with 3 MU IFN t.i.w.
      for 1 year; Group 7, 97 patients with genotype 1 and viraemia > 1,000,000
      GenEq/ml treated with 5 MU IFN daily for 2 months followed by 5 MU t.i.w. for a
      further 10 months. RESULTS: According to an intention-to-treat analysis, a
      sustained virological response (negative HCV-RNA by polymerase chain reaction 6
      months after the end of therapy) was observed in 42% of Group 1 patients, in 21%
      of Group 2 patients versus 24% of Group 3 patients [P = not significant (NS)], in
      28% of Group 4 patients versus 35% of Group 5 patients (P = NS), and in 8.5% of
      Group 6 patients versus 12% of Group 7 patients (P = NS). CONCLUSIONS: Even
      though a trend towards a therapeutic improvement is observed, the adoption of
      more aggressive IFN protocols, such as induction therapy, does not appear to
      significantly improve the rate of sustained response in patients with chronic
      hepatitis C associated with HCV genotype 1 and highly viraemic levels compared
      with standard therapy. Moreover, patients with only one unfavourable predictive
      factor (genotype 1 or high viraemia) do not gain major therapeutic benefits when
      treated with high doses of IFN.

PMID- 11246615
TI  - Elevation of cytokeratin 19 fragment in serum in patients with hepatoma: its
      clinical significance.
AB  - OBJECTIVES: Cytokeratin 19 fragment (CK19) levels in serum have already been
      documented as a useful tumour marker for lung cancer. In the present study, we
      hypothesize that CK19 may be increased in serum from patients with hepatoma.
      METHODS: We measured the CK19 levels in serum from patients with hepatoma and
      evaluated the correlation between CK19 level and each clinical parameter. We
      studied 70 patients diagnosed with hepatoma, and used 14 patients with chronic
      hepatitis C and 45 patients with liver cirrhosis as controls. RESULTS: In 33 of
      70 patients (47.1%) with hepatoma, the serum CK19 level was elevated to above the
      normal range. CK19 levels in serum from patients with hepatoma were significantly
      correlated with levels of alpha-fetoprotein and prothrombin induced by vitamin K
      absence for factor II (PIVKA-II). In 57 patients with hepatoma in whom both CK19
      and alpha-fetoprotein were measured, only CK19 was elevated in seven patients
      (12.3%). Immunohistochemical studies using hepatoma tissues demonstrated that
      hepatoma cells were stained by anti-human CK19 antibody. We also demonstrated
      that the HepG2 cell line expressed CK1 9. CONCLUSIONS: Our data demonstrate that
      hepatomas aberrantly express CK19, and that measurement of CK19 might be a useful
      tumour marker in diagnosing hepatoma.

PMID- 11246616
TI  - Haemodynamic effects of propranolol, octreotide and their combination during
      fasting and post-prandial splanchnic hyperaemia in patients with cirrhosis.
AB  - BACKGROUND/AIMS: This double-blind study was designed to evaluate the
      haemodynamic effect of two drugs, propranolol and octreotide, and their
      combination in patients with cirrhosis. METHODS: Fifteen patients with cirrhosis
      were randomly assigned to two groups receiving either octreotide subcutaneously
      at 100 microg ('octreotide' group, n = 9) or propranolol orally at 40 mg followed
      by a subcutaneous dose of octreotide (100 microg) after 1 h ('propranolol +
      octreotide' group, n = 6); then, after 30 min, a standard meal was administered
      to both groups. The hepatic vein pressure gradient by hepatic vein
      catheterization, portal and superior mesenteric artery blood flow velocity,
      superior mesenteric artery pulsatility index by the echo-Doppler duplex system
      were recorded at baseline, 1 h after propranolol in the 'propranolol +
      octreotide' group, and in both groups 30 min after octreotide and 30 min after
      meal. RESULTS: At fast, propranolol was more active in decreasing portal pressure
      (from 16 +/- 2.2 to 12.7 +/- 3.8 mmHg, -20%, P < 0.05) as compared to octreotide
      (from 18.6 +/- 4.8 to 16.6 +/- 4.3 mmHg, -11%, P < 0.05). Conversely, octreotide
      was more active on the mean blood flow velocity of superior mesenteric artery
      (from 22.8 +/- 5 to 19 +/- 4.5 cm/ s, -17%; P< 0.05). Octreotide administration
      in patients receiving beta-blockers showed, also, a trend to increase the
      mesenteric vascular resistances (pulsatility index from 3.14 +/- 0.69 to 3.68 +/-
      1.29, +17%, not significant (NS)) which had not been affected by previous
      treatment with propranolol. After the meal, a reduction of the expected
      hyperaemic response occurred in both groups. CONCLUSIONS: The combined acute
      haemodynamic effect of this association suggests the possible combination of
      these two drugs in critical situations, such as variceal bleeding in patients
      receiving beta-blockers. The simultaneous use of echo-Doppler and hepatic vein
      catheterization permitted us a more complete analysis of the acute haemodynamic
      events.

PMID- 11246617
TI  - No beneficial effects of transdermal nicotine in patients with primary sclerosing
      cholangitis: results of a randomized double-blind placebo-controlled cross-over
      study.
AB  - BACKGROUND/AIMS: Smoking is associated with a decreased risk of primary
      sclerosing cholangitis. We aimed to explore the therapeutic efficacy of and
      tolerance for transdermal nicotine treatment in this disease. METHODS: Twelve
      patients (11 males; 37 +/- 6 years; six with ulcerative colitis) who did not
      achieve complete biochemical remission on ursodeoxycholic acid (14 mg/ kg/day)
      were treated in a randomized cross-over trial with transdermal nicotine (15
      mg/day) or a placebo, each for 8 weeks (4-week washout period between
      treatments). RESULTS: One patient developed de novo ulcerative colitis and two
      did not complete the entire protocol because of intercurrent bacterial
      cholangitis. Baseline values [mean (range)] were: bilirubin, 1.3 (0.5-2.6);
      alkaline phosphatase (APh), 2.5 (1.4-4.7); gamma-glutamyl transpeptidase
      (gammaGT), 7.7 (0.7-38); aspartate aminotransferase (AST), 1.9 (0.5-3.2); alanine
      aminotransferase (ALT), 2.4 (0.4-7.3); and bile salts, 10.9 (2.1 -39) times the
      upper limit of normal. No significant effect on pruritus or fatigue was noted
      during either period, but a small increase in bodyweight was observed during
      placebo treatment. No significant differences were observed between the two
      treatment modalities after 8 weeks in bilirubin (nicotine versus placebo, +13%
      versus -6% change from baseline), APh (-3% versus -17%), gammaGT (-11% versus 
      13%), AST (+2% versus -10%), ALT (-1% versus -11%) or bile salts (+36% versus 
      3%). CONCLUSION: Transdermal nicotine does not seem to have a clear short-term
      beneficial effect in primary sclerosing cholangitis treated with ursodeoxycholic
      acid.

PMID- 11246618
TI  - The racial cohort phenomenon: seroepidemiology of Helicobacter pylori infection
      in a multiracial South-East Asian country.
AB  - BACKGROUND: Malaysia is a multiracial country where three major Asian races live
      together: Malay, Chinese and Indian. In addition, there are a number of native or
      indigenous races, particularly in East Malaysia. Differences in prevalence of
      gastric diseases between races have been noted, particularly with respect to
      peptic ulcer disease and gastric cancer. The aim of this study is to determine
      the prevalence rates and risk factors for Helicobacter pylori infection among
      various races in Malaysia. METHODS: A large-scale prospective seroepidemiological
      study in West and East Malaysia using the HEL-p II commercial enzyme-linked
      immunosorbent assay kit (AMRAD, Melbourne, Australia) to detect H. pylori
      antibodies. Populations surveyed in West Malaysia were a rural community from
      Kuala Pilah, and blood donors from Kuala Lumpur and Kota Baru. Subjects studied
      in East Malaysia were volunteer blood donors from Kota Kinabalu, and blood donors
      and healthy volunteers from Sibu. Statistical analyses using multiple logistic
      regression analysis were carried out to identify independent risk factors for H.
      pylori infection RESULTS: A total of 2,381 subjects were evaluated. H. pylori
      prevalence varied from different areas of study and ranged from a low of 26.4% in
      blood donors from Kota Baru to a high of 55.0% in Kota Kinabalu. The most
      striking differences, however, were noted in the prevalence rates among different
      racial groups. Prevalence rates among the Malays ranged from 11.9 to 29.2%, while
      the Chinese ranged from 26.7 to 57.5%, and those of Indians in two studies were
      49.4 and 52.3%. In every location, Malays had a significantly lower prevalence
      compared with the other races. The highest prevalence rates were recorded among
      the indigenous races in Kota Kinabalu, East Malaysia. There was no difference
      between males and females in the studies. An increasing trend with age was noted
      in the majority of studies; however, no increase in prevalence rates was noted
      among the Malays. CONCLUSIONS: The pattern of infection in a multiracial
      population in Malaysia points to a 'racial cohort' phenomenon. The infection
      appears to be confined to a racial group, with the Malays having consistently low
      prevalence rates. This observation may provide clues to the mode of transmission
      of infection.

PMID- 11246619
TI  - Prevalence of and risk factors for Helicobacter pylori infection among healthcare
      workers at a teaching hospital in Rome: the Catholic University Epidemiological
      Study.
AB  - OBJECTIVES: To evaluate the prevalence of and the risk factors for Helicobacter
      pylori in a population of medical and non-medical workers at a teaching hospital
      in Rome, Italy. DESIGN: A cross-sectional study. METHODS: From January to October
      1998, 655 subjects (65% of the total population) underwent a 13C-urea breath test
      to assess H. pylori infection. Subjects completed a questionnaire concerning
      sociodemographic characteristics, work departments and history of some
      gastrointestinal symptoms. Differences in means and proportions were evaluated
      and independent predictors of H. pylori infection status were assessed by
      multiple logistic regression analysis. RESULTS: Forty percent of the subjects
      were found to be H. pylori infected. The mean age of positive subjects was
      significantly higher than that of negative ones (38 +/- 14 versus 34 +/- 12
      years; P < 0.01). No significant difference was found between males and females
      concerning the infection status (40.2% males versus 39.9% females). Lower years
      of father's education [odds ratio (OR), 3.1; 95% confidence interval (CI), 1.9
      5.1] and age older than 35 years (OR, 2.0; 95% CI, 1.3-3.1) were the only
      independent predictors of the likelihood of H. pylori positivity. Prevalence of
      gastrointestinal symptoms was similar in infected and uninfected subjects.
      Physicians were significantly less infected than nurses and auxiliary personnel
      (26% versus 47% versus 55%, respectively); however, a loss of association was
      observed after adjustment by multiple logistic regression (OR, 1.8; 95% CI, 0.9
      3.7). In all groups, some specific departments appear to be associated with a
      higher infection status. CONCLUSIONS: Among healthcare workers, H. pylori
      infection was associated with specific sociodemographic characteristics, such as
      age and level of father's education. The prevalence of H. pylori infection was
      not associated with different professional categories. However, some specific
      departments seem to increase infection risk.

PMID- 11246621
TI  - Inflammatory bowel disease, azathioprine and skin cancer: case report and
      literature review.
AB  - A 42-year-old blond Caucasian woman taking azathioprine for 8 years developed an
      intra-epidermal carcinoma of the shin. She regularly used a sun bed to maintain a
      tan. Although the increased risk of non-melanoma skin cancer in immunosuppressed
      transplant recipients is well recognized, patients with Crohn's disease are not
      currently warned of the risk of exposure to ultraviolet light. Individuals with
      inflammatory bowel disease who take azathioprine, especially those with a fair
      complexion, should be informed of the potential dangers of sun bathing and should
      be advised to limit sun exposure.

PMID- 11246620
TI  - Infliximab therapy for Crohn's disease in the presence of chronic hepatitis C
      infection.
AB  - Treatment of Crohn's disease with infliximab is an important drug therapy for
      patients with refractory and fistulating disease. There are concerns over its use
      in a proportion of Crohn's patients with concurrent hepatitis C infection, since
      there are theoretical risks of accelerated hepatic decompensation due to the
      immunomodulatory impact of infliximab. We report a patient with both Crohn's
      disease and ongoing active hepatitis C infection who underwent infliximab
      therapy, with no worsening of his liver function or PCR status.

PMID- 11246622
TI  - Virus-like particles in a case of acute hepatitis with human GB virus-C viraemia.
AB  - BACKGROUND/AIMS: It is still controversial whether the human GB virus-C can cause
      liver injury, as in situ demonstration of the virus is still inconclusive.
      METHODS: Here we describe the case report of a patient with two episodes of
      severe acute hepatitis, who had a meticulous clinical, immunological and
      microbiological work-up, including human GB virus-C RNA detection by in situ
      hybridization and electron microscopy. RESULTS: Human GB virus-C viraemia was
      found as the only potential cause of hepatitis in this patient. Furthermore,
      virus-like particles could be demonstrated in the cytoplasm of single hepatocytes
      by electron microscopy and human GB virus-C RNA was detected in the liver by in
      situ hybridization. CONCLUSION: The presence of human GB virus-C RNA in serum
      together with the demonstration of human GB virus-C RNA in the liver, favour
      acute human GB virus-C infection as the cause of liver injury in this patient.
      Thus virus-like particles and hepatic human GB virus-C RNA should be specifically
      looked for by electron microscopy and in situ hybridization, especially during
      the diagnostic work-up of patients with unexplained hepatitis.

PMID- 11246623
TI  - An unusual cause of biliary stricture in a patient with neurofibromatosis type 1.
AB  - The majority of biliary strictures occur as a consequence of iatrogenic injury to
      the extrahepatic biliary tract, with more than 80% following cholecystectomy. The
      laparoscopic era has led to heightened awareness of this problem. The occurrence
      of an iatrogenic stricture can be particularly devastating to both patient and
      surgeon. The literature highlights a number of factors involved in the aetiology
      of such traumatic stricture formation. We report an unusual case of a Bismuth 2
      stricture of the proximal common hepatic duct,occurring in a patient with type 1
      neurofibromatosis, following an iatrogenic bile duct injury that occurred during
      a laparoscopic cholecystectomy. Histological examination of the strictured region
      of bile duct removed at surgery demonstrated multiple neurofibromas of varying
      sizes present in the submucosa. Neurofibromatosis type 1 (von Recklinghausen
      disease) affects the gastrointestinal tract in up to 25% of cases, and in such
      cases is characterized by multiple submucosal neurofibromas. We believe this is
      the first reported case of a biliary stricture in a patient with
      neurofibromatosis type 1, which appeared to be as a consequence of neurofibromas
      in the submucosa of the bile duct.

PMID- 11246624
TI  - Overlap syndrome of primary sclerosing cholangitis and autoimmune hepatitis.
AB  - We report a 46-year-old patient with the typical biochemical, histological and
      cholangiographic findings of primary sclerosing cholangitis (PSC) whose clinical
      and laboratory findings would also qualify her for the diagnosis of definite
      autoimmune hepatitis (AIH), according to the aggregate score of the International
      Autoimmune Hepatitis Group. We suggest that this patient may represent an example
      of the overlapping syndrome of PSC and AIH.

PMID- 11246625
TI  - A malignant gastrointestinal stromal tumour in a patient with multiple endocrine
      neoplasia type 1.
AB  - Loss of heterozygosity for polymorphic markers flanking the multiple endocrine
      neoplasia type 1 (MEN-1) gene in parathyroid and pancreatic islet tumours from
      subjects with MEN-1 has been well documented and has led to the hypothesis that
      the MEN-1 gene functions as a recessive tumour suppressor gene. We report a case
      of MEN-1 with duodeno-pancreatic gastrinoma, parathyroid hyperplasia, pituitary
      adenoma, adrenal adenoma, and lipomas, whose rare association with a malignant
      gastrointestinal stromal tumour (GIST) represents an undescribed combination. MEN
      1 mutation in this family was shown as a frameshift (1607delA) in exon 10. To
      assess the role of the MEN-1 gene in the pathogenesis of tumours less commonly
      associated with MEN-1, we studied GIST DNA for loss of the unaffected MEN-1 gene
      allele. Stromal tumour and peripheral leucocyte DNAs from our patient were
      examined for loss of heterozygosity using the PYGM microsatellite polymorphism
      and an intragenic polymorphism (D418D in exon 9) in the MEN-1 gene. We showed no
      evidence for loss of the wild-type MEN-1 allele in GIST. The MEN-1 germline
      inactivating mutation 1607delA-ter558 in exon 10 was detected in the stromal
      tumour DNA, but no somatic mutation in the wild-type MEN-1 allele in GIST DNA was
      detected. Occurrence of GIST could be consistent with the possibility that this
      MEN-1-related uncommon neoplasm arose independently by a mechanism unrelated to
      the MEN-1 gene.

PMID- 11246626
TI  - Endomysial antibody production after in vitro gliadin challenge.

PMID- 11246627
TI  - The urban diet and Crohn's disease: is there a relationship?
AB  - The aetiology and pathogenesis of Crohn's disease (CD) remain to be elucidated.
      In addition to genetic influences and immune mediated cytokine gene activation,
      various specific and non-specific environmental factors are considered to be
      associated with the induction and/or exacerbation of inflammatory bowel disease
      (IBD). The incidence of CD is higher in urban areas than in the rural,
      environment. Patients with CD have a higher dietary intake of sucrose, refined
      carbohydrates and (omega-6 fatty acids, and reduced intake of fruit and
      vegetables. Elemental and exclusion diets are known to be effective in CD.
      However, patients relapse on returning to a normal diet, which suggests that
      there is something in an ordinary diet which, on penetrating the mucosal defence
      mechanism of the terminal ileum, generates a pathogenic immune process. It has
      been suggested that the urban diet contains large quantities of inert inorganic
      non-nutrient microparticles, such as natural contaminants (soil and dust), food
      additives and anti-caking agents which may combine with intestinal luminal
      components such as bacterial cell wall lipopolysaccharides, to form antigenic
      particles. When these are taken up by mucosal mononuclear cells they can mediate
      immune reactions both locally in the mucosa and in the systemic circulation. In a
      study published in this issue of the journal, CD patients allocated to a low
      microparticle diet experienced a significant reduction in CD activity and the
      requirement for corticosteroids, when compared with the control group on a normal
      diet. The main advantage of the microparticle free diet, when compared with
      elemental and exclusion diets, is its enhanced tolerance by the patients and its
      relatively low cost. The preliminary results may give an explanation for the
      rising incidence of the disease in urban society. The results of an on-going
      multi-centre trial by the authors are awaited with interest.

PMID- 11246628
TI  - Who defines Barrett's oesophagus: endoscopist or pathologist?
AB  - The diagnosis of Barrett's oesophagus has traditionally relied on the
      identification of a 3-cm segment of endoscopically abnormal epithelium (columnar)
      in the distal oesophagus. More recently, the presence of intestinal metaplasia
      has become essential. The importance of the definition relates to the
      identification of the risk of cancer development. These factors are discussed in
      the context of the rising incidence of adenocarcinoma, and the relative
      contributions of endoscopists and pathologists in determining likely progression
      are explored. We also discuss the advances in endoscopic technology that may aid
      the endoscopist in predicting malignant progression.

PMID- 11246629
TI  - Environmental Mutagen Society 32nd Annual Meeting. San Diego, California, USA.
      March 16-21, 2001. Abstracts.

PMID- 11246631
TI  - New safety and error reduction standards for hospitals.

PMID- 11246630
TI  - [Bronchiolitis in infants. How to improve the organization of care?].

PMID- 11246632
TI  - Improving educational efforts.

PMID- 11246633
TI  - Continuum of care requirements revised across manuals.

PMID- 11246634
TI  - Scoring definitions revised for all accreditation manuals.

PMID- 11246635
TI  - What is a type I and how do you clear one?

PMID- 11246636
TI  - Taking a look at pain in your organization.

PMID- 11246637
TI  - Using data to prevent a sentinel event with high-risk patients.

PMID- 11246638
TI  - Cumulative author, subject, compound and special issue indexes volumes 852-900
      (1999-2000).

PMID- 11246639
TI  - Singlet oxygen induces oxidation of cellular DNA.
AB  - The aim of the present work was to evaluate the potential for (1)O(2) to induce
      oxidation of cellular DNA. For this purpose cells were incubated in the presence
      of a water-soluble endoperoxide whose thermal decomposition leads to the
      formation of singlet oxygen. Thereafter, DNA was extracted and the level of
      several modified DNA bases was determined by HPLC analysis coupled to a tandem
      mass spectrometric detection. A significant increase in the level of 8-oxo-7,8
      dihydro-2'-deoxyguanosine was observed upon incubation of the cells with the
      chemical generator of (1)O(2), whereas the level of the other DNA bases measured
      remained unchanged. To demonstrate that singlet oxygen is directly involved in
      the formation of 8-oxo-7, 8-dihydro-2'-deoxyguanosine, the corresponding (18)O
      labeled endoperoxide was used. Incubation of the cells with such a generator of
      (18)O-labeled singlet oxygen results in the formation of (18)O-labeled 8-oxo-7,8
      dihydro-2'-deoxyguanosine in the nuclear DNA. This result clearly demonstrates
      that singlet oxygen, when released within cells, is able to directly oxidize
      cellular DNA.

PMID- 11246640
TI  - Cystic fibrosis critical care: no longer an oxymoron.

PMID- 11246641
TI  - Reevaluation of outpatients with Streptococcus pneumoniae bacteremia.

PMID- 11246642
TI  - Subdural hematomas and glutaric aciduria type I.

PMID- 11246643
TI  - Aseptic meningitis.

PMID- 11246644
TI  - Pulmonary hypertension-hyperventilation versus alkali infusion.

PMID- 11246645
TI  - Hospitalists.

PMID- 11246646
TI  - Prostate sampling to predict radical prostatectomy outcome.

PMID- 11246647
TI  - Older adults' multiple stereotypes of young adults.
AB  - Although the nature of younger adults' attitudes toward older adults has been
      researched extensively, there are long-neglected questions regarding older
      adults' views of young adults. In the first phase of this three phase study,
      community dwelling seniors generated traits they believed characterized young
      people. In the second phase, a subsample of the original participants sorted the
      traits into groups that could be found in one and the same young person. Fifteen
      stereotypes appeared when these results were submitted to hierarchical cluster
      analysis. In the final phase, a subsample of the original older adult
      participants rated how typical each of the stereotypes was of younger people. As
      well, each of the stereotypes were rated using an abbreviated version of Kogan
      and Wallach's (1961) semantic differential scale. Results indicate that the
      stereotypes older people hold of younger people are generally more positive than
      negative. Further, the positive stereotypes are viewed as more typical of younger
      adults than are the negative stereotypes.

PMID- 11246648
TI  - Prognostic factors of effectiveness of a support program for caregivers of
      dementia patients.
AB  - In a randomized controlled study, positive effects were found of a support
      program for caregivers of dementia patients. The aim of this study is to identify
      in a secondary analysis the prognostic factors of success of the support program
      by comparing characteristics of patients and primary caregivers for whom the
      support program was effective with those for whom the program was not effective
      (n = 49 pairs of patients and caregivers). The theoretically based individualized
      support program which is presented in this article, was most effective with
      regard to primary caregivers' sense of competence for females sharing a household
      with the dementia patient. The program was most effective in reducing the number
      of patient admissions when patients did not receive support from a district nurse
      and the primary caregivers experienced less emotional support from the informal
      network. A proactive approach by offering this flexible support before caregivers
      ask for support may prolong the stage in which they feel able to care for
      patients at home. Offering this support to females, who usually are supposed to
      care for the patient without assistance, may be both effective and efficient.

PMID- 11246649
TI  - Stressful events and depressive symptoms among old women and men: a longitudinal
      study.
AB  - Depression is quite common among the elderly members of Hong Kong Chinese
      society. This study examined the impact of a series of common stressful life
      events (SLEs) on changes in depressive symptoms among the older people. The
      respondents were 260 people aged seventy years or older from a longitudinal study
      of a representative community sample of the elderly population in Hong Kong.
      Using multiple regression models, the authors found that, of eight SLEs examined,
      only widowhood was associated with depressive symptoms three years later, even
      after controlling sociodemographic, physical health status, and social support
      variables were applied. In addition, the SLE influenced the depression
      differently for men and women, as we found that the death of a spouse was
      associated with increased in depressive symptoms among elder women, and the
      moving out of children was associated with a decrease in depressive symptoms
      among old men. Finally, we also found a close relationship between number of SLEs
      and depression.

PMID- 11246650
TI  - A path model of elder caregiver burden in Indian/Pakistani families in the United
      States.
AB  - Caregiver burden can be seen and analyzed within a cost/reward exchange
      framework. Within this context of caregiving the importance of relationship
      quality as a determinant of burden was examined for 118 Indian/Pakistani
      families. The quality of relationship between the caregiver and the elderly
      emerged as a key factor in predicting burden. Other factors predicting burden
      were gender, role overload, role conflict, and health problems of the elder. In
      addition, it was found that there were several indirect effects through
      relationship quality that predicted burden: support tasks by elder, role
      conflict, and gender of the caregiver.

PMID- 11246651
TI  - Effective communication and counseling with older adults.
AB  - Age-sensitive communication skills must be developed to achieve greater
      effectiveness in assisting older adults. These skills should be guided by
      research findings on the development changes related to normal aging. A listening
      responding technique is presented outlining six principles that can be applied in
      a wide variety of situations. These principles are governed by the intention to
      preserve self-esteem and to clarify the needs of elderly clients. By using this
      approach with the older adult, the practitioner will achieve an effective
      communication process that generates accurate information, supports self
      determination, and achieves a therapeutic process.

PMID- 11246652
TI  - Whiplash and the clinician.

PMID- 11246653
TI  - Occupational low back pain.

PMID- 11246654
TI  - Globalization of rheumatology: activities of ILAR. Think global--act local.
      International League of Associations for Rheumatology.

PMID- 11246655
TI  - HLA-DRB1 alleles encoding an aspartic acid at position 70 protect against
      development of rheumatoid arthritis.
AB  - OBJECTIVE: To determine whether the association between rheumatoid arthritis (RA)
      and HLA-DRB1 is influenced by the amino acid residue encoded at position 70
      (beta70) of the third hypervariable region (HVR3) of the HLA-DRbeta chain.
      METHODS: The frequencies of HLA-DRB1 alleles encoding different amino acid
      residues at beta70 were compared between patients with RA and controls in a
      population from the UK and in a confirmatory population from northwestern Spain.
      HLA-DRB1 typing was done by polymerase chain reaction methods on 476 clinic based
      patients with RA and 180 healthy controls from Staffordshire and Cheshire in the
      UK, and on 179 clinic patients and 145 controls from Lugo, Spain. Associations
      were investigated using chi-square analyses and regression analyses. The extended
      Mantel-Haenszel procedure was used for trend analysis. RESULTS: Carriage of 2
      shared epitope (SE)+ alleles encoding a glutamine at beta70 (Q70SE+/Q70SE+) was
      associated with the greatest risk of RA in the UK and Spanish population (odds
      ratios 7.93 and 4.66, respectively), while possession of 2 SE- alleles encoding
      an aspartic acid at beta70 (D70SE-D70SE-) was associated with the lowest risk (OR
      0.23 and 0.34, respectively). In individuals carrying one SE+ allele and an
      accompanying D70SE- allele there was no increased risk of developing RA [OR 0.93
      (UK) and 1.30 (Spain)]. Possession of D70SE- was more strongly protective than
      possession of Q70SE. Analysis of trend indicated that the strength of association
      of different DRB1 genotypes with RA could be ranked in order (from Q70SE+/Q70SE+
      to D70SE-/D70SE-) according to which amino acid residues were encoded at beta70,
      and whether or not they formed part of a SE sequence. The severity of
      radiographic damage could not be ranked in the same fashion. CONCLUSION: The
      amino acid residue at position 70 of the HVR3 in HLA-DRbeta molecules influences
      susceptibility to RA. The strength of the association of DRB1 genotypes with RA
      is dependent not only on SE status, but also on which amino acid residues are
      encoded at beta70 of the DRB1 alleles. Presence of an aspartic acid residue at
      beta70 protects against development of RA. However, the severity of erosive
      damage does not appear to be associated with the amino acid substitution at 1370.

PMID- 11246657
TI  - Rheumatoid arthritis at a time of passage.
AB  - OBJECTIVE: To determine the relationship of what has been called pre-Columbian
      Old World rheumatoid arthritis (RA) to the RA identified in pre-Columbian North
      America. METHODS: All published claims of pre-Columbian Old World RA were
      reviewed against the established North American standard for its recognition in
      archeologic sites. Those characteristics included polyarticular symmetrical
      marginal erosions [in the absence of subchondral erosions, peripheral joint
      fusion, or axial skeletal involvement (C1-2 excepted)], but requiring the
      presence of perilesional osteopenia on radiographic examination. T test and
      Fisher's exact test were used to assess the significance of the extent of joint
      distribution and the presence of subchondral erosions, peripheral joint fusion,
      and axial disease in the Old World cases that some have claimed represent RA.
      RESULTS: Old World reports of alleged RA often describe isolated bones or
      isolated "finds" without epidemiologic consideration. Subchondral erosions were
      present in 95%. The 2 cases without subchondral erosions had peripheral joint
      fusion and axial joint disease. Peripheral joint fusion and axial joint
      involvement were present in almost all cases. Perilesional sclerosis was actually
      quite prominent, as was other evidence of reactive new bone formation, but not
      perilesional osteopenia. CONCLUSION: As the pre-Columbian Old World erosive
      arthritis is clearly a different phenomenon from what has been documented in the
      New World, the issue appears to relate to criteria for naming RA. There clearly
      are 2 distinct groups that some classify under the broad banner of RA. As the Old
      World variety is indistinguishable from spondyloarthropathy, it is suggested that
      the Old World cases should be recategorized with spondyloarthropathy and that
      only the variety reported in archeologic sites in North America be classified as
      RA.

PMID- 11246656
TI  - Abundant expression of common cytokine receptor gamma chain (CD132) in rheumatoid
      joints.
AB  - OBJECTIVE: Activated macrophages upregulate surface expression of common cytokine
      receptor gamma chains (gammac, CD132), triggering of which induces secretion of
      proinflammatory cytokines. Rheumatoid synovial tissues contain a number of
      macrophages that play a pathogenic role by secreting proinflammatory cytokines.
      We studied the expression of gammac in the rheumatoid synovial tissues. METHODS:
      Cryosections of synovial tissues from patients with active rheumatoid arthritis
      (RA) or with osteoarthritis (OA) were stained with an anti-gammac Mab. Single
      cell suspensions from the rheumatoid synovial tissues were stained with the same
      antibody and an anti-CD14 monoclonal antibody (Mab) for 2-color flow cytometric
      analysis. A soluble form of gammac in synovial fluids collected from rheumatoid
      or OA joints was quantitated by ELISA. RESULTS: Rheumatoid synovial tissues, but
      not the OA tissues, expressed gammac at a high level. Flow cytometric analysis
      showed that gammac were expressed by virtually all CD 14 positive synovial cells
      in RA. Synovial fluid derived from the rheumatoid joints contained a high
      concentration of soluble gammac. CONCLUSION: Membrane bound and soluble forms of
      gammac are abundant in rheumatoid joints. They might play a complex role in the
      pathology of RA.

PMID- 11246658
TI  - Methotrexate (MTX) inhibits osteoblastic differentiation in vitro: possible
      mechanism of MTX osteopathy.
AB  - OBJECTIVE: To clarify the mechanism of impaired bone formation during low dose
      methotrexate (MTX) therapy. METHODS: The in vitro effects of MTX on the function
      and differentiation of osteoblastic cells were investigated using (1) a mouse
      osteogenic cell line (MC3T3-E1) with the capacity to differentiate into
      osteoblastic or osteocytes, (2) a human osteoblastic osteosarcoma cell line (SaOS
      2) with a mature osteoblastic phenotype, and (3) mouse bone marrow stromal cells
      containing osteoblast precursors. Osteoblast function was assessed by measuring
      the cellular activity of alkaline phosphatase (ALP) and the mineralization
      capacity of cultures. RESULTS: MTX suppressed ALP activity dose-dependently in
      growing MC3T3-E1 cells, but proliferation of these cells was only inhibited by a
      high concentration of MTX. In contrast, inhibition of ALP activity in MC3T3-E1
      cells of mature osteoblastic phenotype was only observed with 10(-8) M and 10(-7)
      M MTX, and proliferation was not influenced. ALP activity and the proliferation
      of SaOS-2 cells were not inhibited by MTX, even when growing cells were treated.
      However, both ALP activity and formation of calcified nodules in bone marrow
      stromal cell cultures were significantly suppressed by MTX at concentrations
      between l0(-10) and 10(-7) M. CONCLUSION: These results suggest that MTX
      suppresses bone formation by inhibiting the differentiation of early osteoblastic
      cells.

PMID- 11246659
TI  - Treatment of systemic lupus erythematosus with LJP 394.
AB  - OBJECTIVE: LJP 394 is a novel therapy under development for the treatment of
      systemic lupus erythematosus (SLE). We investigated the optimal LJP 394 dosing
      regimen required to maximally reduce serum dsDNA antibodies. We also evaluated
      the safety and tolerability of repeated doses of LJP 394 as well as the effects
      of therapy on SLE related disease activity and health related quality of life.
      METHODS: This was a multicenter, partially randomized, placebo controlled, double
      blind, dose-ranging trial. Study drug or placebo was administered at weekly,
      biweekly, or monthly intervals for a total of 17, 9, or 5 doses, respectively.
      Fifty-eight patients were randomly assigned to receive 1, 10, or 50 mg LJP 394 or
      placebo. After a 2 month pretreatment period, dosing visits continued for 16
      weeks, after which there was a 2 month posttreatment period. RESULTS: The
      greatest reductions in mean dsDNA antibody titers were observed in the group of
      patients who received 50 mg LJP 394 weekly (38.1% and 37.1 % at Weeks 16 and 24,
      respectively). A reduction (29.3%) in dsDNA antibody titers was also observed at
      Week 24 in the group of patients who received 10 mg LJP 394 weekly. The
      frequencies of adverse events were comparable in the placebo and active treatment
      groups. CONCLUSION: This clinical trial, in which a large number of patients with
      SLE were treated with LJP 394, expanded the safety profile of LJP 394 and
      demonstrated its capacity to reduce dsDNA antibodies.

PMID- 11246660
TI  - Disease course in systemic lupus erythematosus: changes in health status, disease
      activity, and organ damage after 2 years.
AB  - OBJECTIVE: To examine changes in health status, disease activity, and organ
      damage after 2 years and to study possible disease variables predicting change in
      health status, disease activity, and organ damage at followup in systemic lupus
      erythematosus (SLE). Second, to compare changes in health status in patients with
      SLE to that of matched patients with rheumatoid arthritis (RA) and matched
      healthy controls. METHODS: A 2 year longitudinal observational study, measuring
      health status (Short-Form 36. visual analog scale for pain and fatigue, modified
      Health Assessment Questionnaire, patient global assessment of disease activity),
      disease activity, and organ damage in 87 patients with SLE. Health status
      measures in SLE were compared to 65 matched RA patients selected from the Oslo RA
      register and to 77 matched healthy controls from the population register.
      RESULTS: On a group level the SLE patients showed stable health status measures
      and disease activity scores 2 years after baseline, but organ damage scores
      increased significantly. Increase in organ damage was significantly and
      independently predicted by baseline scores of disease activity and organ damage,
      health status, and disease activity by the respective baseline scores. Changes in
      health status measures over 2 years were similar in SLE, RA, and healthy
      controls. CONCLUSION: Our 2 year longitudinal observational SLE study showed a
      stable course of health status and disease activity, whereas organ damage
      increased. Disease activity and organ damage at baseline predicted the latter.
      Our results indicate the value of careful monitoring of disease activity over
      time in SLE and individually tailored treatment guided by the predictors of
      course and outcome.

PMID- 11246661
TI  - Selective reduction and recovery of invariant Valpha24JalphaQ T cell receptor T
      cells in correlation with disease activity in patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: To study the regulatory role of CD4-CD8- double-negative (DN)
      invariant T cell receptor (TCR) Valpha24JalphaQ T cells, a human counterpart of
      murine NK 1 + T cells, in the autoimmune process of systemic lupus erythematosus
      (SLE). METHODS: We carried out a 2 step frequency analysis of DN Valpha24JalphaQ
      T cells in patients with SLE before and after prednisolone therapy; the frequency
      of DN Valpha24+ T cells was determined by 3 color FACS analysis and subsequently
      the frequency of Valpha24JalphaQ rearrangement among DN Valpha24+ T cells was
      determined by sequencing. RESULTS: DN Valpha24+ T cells were significantly
      increased in patients with active SLE compared to healthy subjects. In healthy
      subjects, invariant Valpha24JalphaQ TCR dominated in DN Valpha24+ T cells at a
      high frequency (93-100%). However, the invariant Valpha24JalphaQ TCR was not
      detected in DN Valpha24+ T cells from patients with active SLE, and instead 2 to
      9 Jalpha genes other than the invariant JalphaQ were oligoclonally expanded in
      the patients. In inactive SLE induced by prednisolone therapy, the invariant
      Valpha24JalphaQ TCR could be detected in DN Valpha24+ T cells from all the
      patients and dominated in most of the patients. Further, oligoclonally expanded
      Valpha24+ clones other than the invariant JalphaQ gene in active disease states
      were significantly decreased by prednisolone therapy. CONCLUSION: The selective
      reduction of DN invariant Valpha24JalphaQ T cells is related to the disease
      progression of SLE, while DN TCR Valpha24 T cells other than Valpha24JalphaQ T
      cells constitute autoaggressive T cells in SLE.

PMID- 11246662
TI  - Autoantibodies within families of patients with systemic lupus erythematosus are
      not directed against the same nuclear antigens.
AB  - OBJECTIVE: The presence of antinuclear autoantibodies in systemic lupus
      erythematosus (SLE) is influenced by genetic factors. The presence of
      autoantibodies in healthy family members of patients has been reported. Our
      hypothesis was that autoantibodies are directed against the same antigens in
      first-degree family members of patients with SLE as in their patient relative.
      METHODS: Plasma was harvested from 50 patients with SLE, 154 unaffected first
      degree family members, and 330 healthy controls. Presence of autoantibodies
      against 14 specific nuclear antigens was tested by the ELISA based line
      immunoassay INNO-LIA method. RESULTS: Seventy-four percent of patients, 32% of
      first-degree family members, and 1.5% of healthy controls had antibodies against
      any nuclear antigen. Most frequent autoantibodies in the patients were anti
      histone and anti-SSA, whereas in the family members these were anti-RNP-C and
      anti-Topo-I/Scl. Presence and specificity of autoantibodies in family members
      were independent of the presence or absence of that autoantibody in their patient
      relative (chi-square p > 0.1 for all 14 antigens). CONCLUSION: Autoantibodies in
      family members and their patient relatives are not directed against the same
      nuclear antigens. Thus a familial aspecific dysfunction of the B lymphocyte is
      the most likely explanation for autoantibody production in SLE.

PMID- 11246663
TI  - Telomerase activity in peripheral blood mononuclear cells of systemic connective
      tissue diseases.
AB  - OBJECTIVE: Telomerase activity has been detected in a large number of cancers, as
      well as human germline tissue, but is absent in most normal somatic tissue. It
      has been reported that telomerase is also expressed at a low level in normal
      peripheral blood lymphocytes and that its activity is increased by antigen
      processing. We investigated if the telomerase activity in peripheral blood
      mononuclear cells (PBMC) from patients with systemic connective tissue diseases
      reflects disease activity. METHODS: We examined the enzyme activity of PBMC from
      patients with systemic lupus erythematosus (SLE), mixed connective tissue disease
      (MCTD), primary Sjogren's syndrome (SS), and systemic sclerosis (SSc) using the
      telomeric repeat amplification protocol. In SLE and SS patients, the telomerase
      activity level was assessed for correlations with clinical disease activity.
      RESULTS: Telomerase activity was detected in 64.7% (11/17) of SLE patients, 63.6%
      (7/11) of MCTD, 54.5% (6/11) of SS, and 44.4% (4/9) of SSc. There was a
      significant correlation between SLE Disease Activity Index scores and telomerase
      activity in patients with SLE (p < 0.01). In patients with SS, telomerase
      activity was detected predominantly in patients with extraglandular
      manifestations, but was less detectable in patients without extraglandular
      manifestations (p < 0.05). CONCLUSION: Our data show that telomerase activity of
      PBMC is an indicator of disease activity, and may play a role in pathogenesis of
      systemic connective tissue diseases.

PMID- 11246664
TI  - Lack of relationship between functional ability and skin score in patients with
      systemic sclerosis.
AB  - OBJECTIVE: To examine the hypothesis that functional ability is related to skin
      score in patients with systemic sclerosis (SSc). METHODS: In 140 patients with
      SSc attending clinics in the northwestern region of England, functional ability
      (measured using a recently developed 11 item functional questionnaire) was
      correlated with skin score (measured using a modified Rodnan technique--17 sites,
      maximum score 3 for each site). RESULTS: The median functional score was 6 (range
      0-31) and the median skin score 7 (range 0-37). There was no correlation between
      functional score and total skin score (rS = 0.11, p = 0.19, Spearman). Because
      most of the questions of the functional score related to upper limb function,
      separate analyses were undertaken restricting consideration of skin involvement
      to (1) upper limbs only and (2) digital skin only, versus the overall functional
      score. Again, no evidence of an association was observed. CONCLUSION: Functional
      ability in this broad group of patients with SSc cannot be predicted from the
      skin score. Although skin score is useful prognostically, it is not a major
      determinant of a patient's ability to perform activities of everyday living.

PMID- 11246665
TI  - Sympathetic dysfunction in patients with primary Sjogren's syndrome.
AB  - OBJECTIVE: To investigate autonomic nervous system function in patients with
      primary Sjogren's syndrome (SS) and relate the findings to clinical variables.
      METHODS: Autonomic nervous system function was determined in 30 patients with
      primary SS using the finger skin blood flow test [vasoconstrictory (VAC) index],
      deep-breathing test [expiration/inspiration (E/I) ratio], and the tilt table
      (orthostatic) test [acceleration index (AI), brake index (BI), and orthostatic
      blood pressure]. The results were compared with age matched control materials
      (finger skin blood flow test, n = 80, and deep-breathing and tilt table tests, n
      = 56). RESULTS: The VAC index was found to be significantly increased and the E/I
      ratio significantly decreased in patients compared to controls, indicating both a
      sympathetic and a parasympathetic dysfunction. Further, the patients, especially
      the anti-SSA and anti-SSB antibody seropositives, were found to have an abnormal
      blood pressure reaction to tilt compared to controls. No correlations were found
      between autonomic nerve function variables measured and the clinical
      ophthalmologic or the oral tests, performed at the time of diagnosis. CONCLUSION:
      Patients with primary SS show signs of both sympathetic and parasympathetic
      dysfunction. Further, immunological mechanisms seem to influence blood pressure
      in patients with primary SS.

PMID- 11246666
TI  - Autoantibodies to receptor induced neoepitopes of fibrinolytic proteins in
      rheumatic and vascular diseases.
AB  - OBJECTIVE: Abnormal plasminogen activation has been implicated in vascular and
      rheumatic diseases. The development of an autoimmune response to neoepitopes of
      plasminogen and its activator (tissue-type plasminogen activator, t-PA) was
      explored in sera from patients with rheumatoid arthritis (RA, n = 30), Behcet's
      disease (n = 20), primary antiphospholipid syndrome (APS, n = 23), and idiopathic
      arterial (n = 33) or venous thrombosis (n = 16). METHODS: Sera diluted 1/50 were
      incubated with either plasminogen or t-PA bound to their natural receptors
      (immobilized fibrin or monocytic cells), and bound immunoglobulins were detected
      using a sheep peroxidase labeled anti-human Fab IgG. Controls included plates
      coated with fibrin or cells alone or plasminogen passively adsorbed to the
      plastic. Sera were considered positive when the absorbance at 405/490 nm was
      above the mean + 2 SD of normal sera. RESULTS: Reactivity of sera against
      plasminogen bound to cells (28%) or to fibrin (22%) was a predominant feature in
      patients with RA compared with other patient groups and controls. However, some
      patients with primary APS had reactivity against cell and fibrin bound
      plasminogen (9 and 13%, respectively). Autoantibodies against fibrin bound t-PA
      were detected in only 8% of patients with arterial or venous thrombosis.
      CONCLUSION: Conformational changes induced by molecular assembly of plasminogen
      on cell or fibrin surfaces result in the expression of neoepitopes recognized by
      autoantibodies. These autoantibodies could be markers of the proteolytic events
      associated with plasminogen activation in autoimmune diseases.

PMID- 11246667
TI  - Uveitis as a cause of visual loss in arthritides and comparable conditions.
AB  - OBJECTIVE: To examine the role of inflammatory rheumatic diseases and comparable
      conditions in the etiology of severe uveitis leading to visual impairment and
      blindness. METHODS: A retrospective study based on the Finnish Register of Visual
      Impairment. At the end of 1996, the Finnish Register of Visual Impairment
      included 296 uveitis patients in whom uveitis was the main cause of visual
      impairment. The patient records were examined retrospectively to investigate the
      etiology of severe uveitis. Due to the incompleteness of data obtained of the
      patients blinded a long time ago, we included only 174 uveitis patients whose
      visual handicap (best corrected visual acuity in the better eye < 20/60 or severe
      visual field loss) was stated during 1980-1996. RESULTS: A total of 174 uveitis
      patients were found, 72 male and 102 female. A diagnosed or presumed inflammatory
      rheumatic disease or comparable condition was found in 38/174 (22%) patients:
      juvenile rheumatoid arthritis in 14 (8%), spondyloarthropathy (ankylosing
      spondylitis or reactive arthritis) in 10 (6%), sarcoidosis in 5 (3%),
      seronegative rheumatoid arthritis in 4 (2%); Behcet's disease was diagnosed in 2
      (1%), 1 patient had polymyositis, 1 polyarteritis nodosa, and 1 juvenile systemic
      lupus erythematosus. In addition to the above, 10 (6%) patients had chronic back
      pain and 5 (3%) patients various noninflammatory joint problems. Diverse other
      ophthalmologic or systemic disease was detected in 38 (22%) cases. Trauma or
      surgery caused uveitis in 9 (5%) patients. For 74/174 (43%) uveitis patients no
      specific associating condition could be shown. Legal blindness was documented in
      65/174 (37%) patients, including 8 totally blind persons. CONCLUSION: This study
      provides first data on the relative importance of inflammatory rheumatic diseases
      and comparable conditions in the etiology of severe uveitis leading to visual
      handicap and blindness.

PMID- 11246668
TI  - Association between vitiligo and spondyloarthritis.
AB  - OBJECTIVE: To establish if spondyloarthritis (SpA) and vitiligo occur together
      more frequently than by chance. METHODS: All consecutive patients with SpA seen
      in a 6 month period were evaluated for vitiligo by an experienced dermatologist.
      The control group included the 2 consecutive patients without SpA seen after each
      patient with SpA. RESULTS: Two hundred thirty-four patients with SpA (131 men,
      103 women; mean age 59 +/- 18.3 yrs) were seen in the study period. Of these, 43
      had ankylosing spondylitis (AS), 112 psoriatic arthritis (PsA), 14 SpA associated
      with inflammatory bowel disease, 64 undifferentiated SpA, and one reactive
      arthritis. The 468 control patients (360 women, 108 men; mean age 68.5 +/- 2 yrs)
      had various degenerative and inflammatory rheumatic diseases. Eight (3.4%)
      patients out of 234 with SpA had type A vitiligo. In the control group, 5 (1.06%)
      out of 468 had type A vitiligo. The difference was statistically significant (p <
      0.05). Of the 8 patients with coexisting vitiligo and SpA, 4 had PsA, 2 primary
      AS, one AS associated with Crohn's disease, and one undifferentiated SpA. Of the
      5 patients with vitiligo in the control group, one had rheumatoid arthritis, one
      S ogren's syndrome, one palindromic rheumatism, one crystal arthropathy, and one
      osteoarthritis. CONCLUSION: Our results suggest that vitiligo and SpA do not
      coexist by chance and that vitiligo should be included in the list of diseases
      associated with SpA.

PMID- 11246669
TI  - Risk factors for work disability in patients with ankylosing spondylitis.
AB  - OBJECTIVE: To identify risk factors for work disability in patients with
      ankylosing spondylitis (AS). METHODS: Risk factors for permanent work disability
      and for receipt of disability payments were assessed using Cox regression models
      in a retrospective cohort study of 234 patients with AS. Candidate risk factors
      included age at onset of AS, sex, race, education level, marital status, the
      presence of comorbid conditions, smoking and drinking history, recreational
      activity, occupation, and physical activity at work. Risk factors for changes in
      the type of work performed, decrease in number of hours worked, long sick leave,
      and the need for help at work were assessed using logistic regression models in a
      prospective study of the subset of 144 patients who reported working for pay
      during the study. Candidate risk factors for these aspects of work disability
      were age, sex, race, education level, levels of functional disability, pain and
      stiffness, changes in functional disability, pain or stiffness over the preceding
      6 months, minutes/week of recreational exercise, back exercises, freedom of
      movement at work, control over the pace of work, and physical activity at work.
      RESULTS: In a cohort of 234 patients with a median duration of AS of 21.4 years,
      31 patients (13.2%) developed permanent work disability and 57 patients (24.3%)
      had received disability payments. Older age at onset of AS, less formal
      education, and having had jobs that were more physically active were significant
      risk factors for permanent work disability. These factors, along with the
      presence of a comorbid condition and being female, were also significantly
      associated with the receipt of disability payments. In a prospective study of 144
      patients followed for a median of 4 years, higher levels of functional disability
      and pain were associated with increased risks of decreased work hours, long sick
      leaves, and needing help at work, while higher levels of pain were also
      associated with an increased risk of changing the type of work performed. Women
      were significantly more likely than men to change their type of work or decrease
      their work hours. Patients whose jobs were more physically demanding were more
      likely to change their type of work or need help at work. CONCLUSION: Patients
      with AS who have physically demanding jobs are more likely to experience
      permanent or temporary work disability, or need to change the type of work done
      or receive help at work, than those with jobs that are less physically demanding.

PMID- 11246670
TI  - Diagnostic value of ferritin and glycosylated ferritin in adult onset Still's
      disease.
AB  - OBJECTIVE: To determine the usefulness of serum ferritin and glycosylated
      ferritin (GF) levels in diagnosing adult onset Still's disease (AOSD). METHODS:
      We performed a retrospective multicenter study of 205 patients who had ferritin
      and GF assays in one hospital laboratory. Records of all patients were reviewed,
      and a standardized questionnaire used to extract all data available at the time
      of the assay. The clinicians' final diagnosis was also recorded. Patients were
      classified as having "certain AOSD" (based on Yamaguchi's criteria) or a control
      disease. The concordance of ferritin and GF levels with final diagnosis was
      evaluated. RESULTS: In total 49 AOSD and 120 control patients were eligible. The
      mean ferritin value was significantly higher in the AOSD group (4,752 +/- 9,599
      microg/l) than in the control group (1,571 +/- 3,807 microg/l), p = 0.029. GF was
      significantly lower in AOSD patients (15.9 +/- 11.9%) than in the control group
      (31.5 +/- 18.7%), p < 0.001. The combination of a GF level of < or = 20% with
      ferritin above the upper limit of normal yielded a sensitivity of 70.5% and
      specificity of 83.2%. The combination of a GF level < or = 20% with ferritin 5
      times normal produced a sensitivity of 43.2% and specificity of 92.9%. This
      latter combination allowed an AOSD diagnosis to be ruled out for 6 of the 8
      control patients who met Yamaguchi's positive criteria. CONCLUSION: Ferritin and
      GF levels are powerful diagnostic markers of AOSD. They may be helpful in
      clinical practice for excluding differential diagnoses.

PMID- 11246671
TI  - Expression of transduced HSP70 gene protects chondrocytes from stress.
AB  - OBJECTIVE: To investigate the efficacy of adenovirus vector mediated transduction
      of heat shock protein 70 (HSP70) gene to human chondrocyte-like cell (HCS-2/8)
      against heat stress. METHODS: Two adenovirus vectors that contain wild-type
      (AxSHEwt) or mutant-type (AxSHEmt) HSP70 gene, and that are regulated by SRalpha
      promoter, were constructed. The mutant-type lacks the area that expresses stress
      durability. One of the 2 adenovirus vectors was added to the cultures of human
      chondrocyte-like cells (HCS-2/8). Heat stress (48 degrees C) was applied to the
      transduced cells for 2 h, and the efficacy of adenovirus vector mediated
      transduction of HSP70 gene against heat stress in the chondrocytes was
      investigated using alamar blue assay and MTT assay. RESULTS: Absorbance levels at
      48 degrees C were 300.3 +/- 51.9 and 1.173 +/- 0.011 in the controls, 278.5 +
      33.8 and 1.217 +/- 0.018 in the AxSHEmt transduced cells, and 349 +/- 14.7 and
      1.371 +/- 0.033 in the AxSHEwt transduced cells. The level in the AxSHEwt
      transduced cells was significantly higher than in the other 2 groups (p < 0.05).
      With 37 degrees C treatment, no significant difference was observed. CONCLUSION:
      Chondrocytes to which HSP70 gene was transduced had a significantly higher
      metabolic activity and viability under heat stress.

PMID- 11246672
TI  - Minocycline inhibits the production of inducible nitric oxide synthase in
      articular chondrocytes.
AB  - OBJECTIVE: To determine the in vitro effects of tetracyclines and nonsteroidal
      antiiflammatory drugs on interleukin 1alpha (IL-1alpha) induced NO production and
      biosynthesis of inducible NO synthase (iNOS) by articular chondrocytes. METHODS:
      Bovine chondrocytes were cultured in alginate beads. Cells were treated with IL
      lalpha in the presence or absence of drugs at various concentrations. Expression
      of mRNA for iNOS was analyzed by reverse transcription polymerase chain reaction
      ELISA. Protein synthesis of iNOS was determined by immunoprecipitation. NO
      production was taken as a measure for the activity of the enzyme. RESULTS:
      Minocycline dose dependently reduced IL-1 stimulated NO production by inhibition
      of the mRNA expression (IC50 = 69.9 microM) and protein synthesis (IC50 = 37.11
      microM) of iNOS. Diclofenac-Na at a concentration of 10 microM only weakly
      reduced nitrite accumulation and mRNA expression of iNOS. No effects were
      observed for tetracycline, doxycycline, and meloxicam. CONCLUSION: Inhibition of
      iNOS in articular chondrocytes may be a new mechanism by which minocycline could
      exert its beneficial effects in the treatment of joint diseases.

PMID- 11246673
TI  - Concentration and localization of YKL-40 in hip joint diseases.
AB  - OBJECTIVE: YKL-40 is a major secretory protein from human chondrocytes and
      synovial fibroblasts. We evaluated the concentrations and localization of YKL-40
      in hip joint diseases, and analyzed the possibility of YKL-40 as a new
      inflammatory joint marker. METHODS: The concentration of YKL-40 in synovial fluid
      (SF) was measured by a sandwich-type ELISA. SF samples were collected from 19
      hips with osteoarthritis (OA) of the hip joint, 21 hips with osteonecrosis of the
      femoral head (ONFH), and 5 hips with failed total hip arthroplasty (failed THA).
      In all cases of failed THA, cartilage tissue in hip joints was removed completely
      during the previous THA. The localization of YKL-40 was determined through
      immunohistochemical analysis using a specific antibody. RESULTS: The mean SF
      concentration of YKL-40 was significantly higher in ONFH and failed THA than in
      OA. Comparison by OA grade was not significantly different. In staging of ONFH,
      Ficat stage III with collapsed femoral head showed significantly higher YKL-40
      concentrations than the other stages. Immunohistochemical studies showed that YKL
      40 was localized in chondrocytes in the superficial and middle layers of the
      cartilage. In the synovium, YKL-40 was localized in fibroblasts and macrophages.
      CONCLUSION: YKL-40 reflects the degree of inflammation rather than cartilage
      metabolism. YKL-40 may be a useful inflammatory marker of hip joint diseases.

PMID- 11246674
TI  - Low back pain: prevalence and risk factors in an industrial setting.
AB  - OBJECTIVE: To examine various factors associated with low back pain (LBP) in an
      industrial setting. METHODS: A cross sectional study was carried out among 1,562
      employees of a large utilities corporation in Ontario using a self-administered
      questionnaire. Abdominal muscle strength was measured using a modified
      sphygmomanometer. Statistical analysis was carried out with Student's t test, chi
      square test, and logistic regression analysis. RESULTS: Among 1,302 male
      employees the lifetime and point prevalence of LBP were 60% and 11%,
      respectively. Low back pain was significantly more prevalent among married
      employees, with more physically demanding jobs, regular lifting, poor general
      health, and past major illness. Abdominal muscle weakness was associated with
      current LBP. The mean time lost from work due to LBP over 5 years was 17 days.
      Sedentary workers developing LBP were more likely to require hospital admission.
      CONCLUSION: This study confirms the high prevalence of LBP in industry and
      identifies several risk factors.

PMID- 11246675
TI  - Whiplash injury and hippocrates: practical points for contemporary practitioners.
AB  - The purpose of this article is to consider how the basic principles used by
      Hippocrates in assessing and managing disease in general and musculoskeletal
      problems in particular relate to the better management of "whiplash injury"
      today. Hippocrates' principles of observing, listening, touching, examining, and
      recording, and finally of considering the patient in his/her past and present
      environment are most relevant for contemporary practitioners, particularly those
      who are asked to assess and/or treat cervical sprain or whiplash injury.

PMID- 11246676
TI  - Women with inflammatory polyarthritis have babies of lower birth weight.
AB  - OBJECTIVE: To assess the effect on fetal outcome, and development of the child
      over the first 8 months of life, of rheumatoid arthritis (RA) during pregnancy.
      METHODS: Women with RA or undifferentiated inflammatory polyarthritis (IP) were
      recruited from throughout the UK and followed prospectively from late pregnancy
      to 8 months postpartum. Matched controls were obtained from general
      practitioners. The babies' health at birth and development at 8 months were
      monitored by the weight, head circumference, and length. Potential confounding
      variables were noted. RESULTS: One hundred thirty-three women with RA or
      undifferentiated IP took part in the study. There were 5 (4%) admissions for
      hypertension during pregnancy and no cases of preeclampsia. Cesarean section was
      common (23%). Matched controls were found for 103 (77%) subjects. There were no
      significant differences between groups in head circumference or length at birth.
      Babies born to women with arthritis had lower mean birth weight than controls
      [3.3 kg (standard deviation 0.5) compared to 3.5 kg (0.4); p = 0.004], even after
      adjustment for potential confounding factors. Within the patient group those
      whose arthritis was in remission had significantly heavier babies than those with
      active disease [mean 3.5 kg (0.5) compared with 3.3 kg (0.5); p = 0.04]. This
      trend was still apparent at 8 months, but differences were no longer
      statistically significant. CONCLUSION: This is the first relatively large
      prospective study of the effects on mother and baby of RA during pregnancy. The
      results suggest that, although disease improves in most women during pregnancy,
      it is still sufficiently active to have a modest negative effect on birth weight.

PMID- 11246677
TI  - Clinical response to etanercept in polyarticular course juvenile rheumatoid
      arthritis.
AB  - OBJECTIVE: To evaluate safety and clinical response to treatment with etanercept
      in the polyarticular course of patients with juvenile rheumatoid arthritis (JRA).
      METHODS: Ten patients were studied (8 female, 2 male; 6 polyarticular JRA, 4
      systemic onset; mean age 13.3 yrs; mean duration of disease 6.6 yrs). Patients
      received 0.4 mg/kg etanercept subcutaneously twice weekly in addition to their
      existing therapeutic regimen. Observed duration of treatment ranged between 4 and
      12 months. RESULTS: Patients tolerated treatment with etanercept well. No serious
      adverse events were noted. Treatment response showed considerable improvement of
      morning stiffness (mean reduction of 96 min approximately equal to -93%) and
      joint counts including swollen joints (delta -8.2 approximately equal to -40%),
      tender joints (delta -9.2 approximately equal to -88%), and total joints (delta 
      9.8 approximately equal to -37%). Laboratory results included decreases in ESR
      (delta -46 mm/h approximately equal to -53%) and improvement of anemia.
      CONCLUSION: Our results confirm etanercept is a powerful adjunct in the therapy
      of polyarticular JRA resistant to conventional treatment regimens.

PMID- 11246678
TI  - Anti-alpha-fodrin autoantibody is an early diagnostic marker for childhood
      primary Sjogren's syndrome.
AB  - OBJECTIVE: alpha-fodrin is a recently identified autoantigen associated with
      adult primary Sjogren's syndrome (SS). We tested whether anti-alpha-fodrin
      antibody could also be used as a diagnostic marker for childhood SS. METHODS: We
      performed immunoblot analysis of sera from 7 patients with childhood primary SS
      using glutathione-S-transferase alpha-fodrin fusion protein as an antigen.
      RESULTS: Anti-alpha-fodrin antibody was detected in sera from all 7 patients with
      childhood primary SS, 2 of 4 with secondary SS, and one of 7 with systemic lupus
      erythematosus, but in no other healthy controls. CONCLUSION: The anti-alpha
      fodrin autoantibody was detected before anti-SSA or SSB antibody became positive;
      thus anti-alpha-fodrin antibody could be a useful marker for the early diagnosis
      of SS.

PMID- 11246679
TI  - Absence of conduction defects in the electrocardiograms [correction of
      echocardiograms] of mothers with children with congenital complete heart block.
AB  - OBJECTIVE: To investigate the association between complete congenital heart block
      (CCHB) in the fetus and adult disease. METHODS: We prospectively studied 111
      consecutive patients with systemic lupus erythematosus (SLE) or a positive
      extractable nuclear antigen (Ro, La, or RNP) attending a connective tissue
      disease (CTD) clinic and 19 patients who had had children with CCHB.
      Electrocardiographs were recorded on all patients and subsequently analyzed
      blindly. RESULTS: There was a significantly shorter PR interval in the mothers of
      children with CCHB compared to patients attending the CTD clinic (p < 0.02).
      There was no significant difference in PR interval between Ro positive and Ro
      negative patients in the CTD clinic. There were no significant differences in QRS
      or QTc duration between mothers with CCHB children and Ro positive or Ro negative
      patients attending the CTD clinic. The shorter PR interval in the mothers with
      CCHB children may be explained by their significantly younger age compared to
      patients in the CTD clinic (p < 0.02, 95% CI) and the lower incidence of CTD.
      CONCLUSION: We were unable to confirm the association between anti-Ro antibodies
      and cardiac conduction defects in adults. This supports theories that CCHB is due
      to vulnerability peculiar to the fetal heart during a particular stage of
      development between 16 and 30 weeks of gestation.

PMID- 11246680
TI  - Effects of inherited thrombophilic mutations in an adolescent with
      antiphospholipid syndrome and systemic lupus erythematosus.
AB  - Thrombophilia can result from either inherited or acquired conditions. We
      describe a teenager who developed extensive thrombosis requiring aggressive and
      prolonged anticoagulation. Laboratory evaluation revealed an acquired lupus
      anticoagulant, consistent with the antiphospholipid antibody syndrome (APS). DNA
      analysis revealed inherited thrombophilic mutations in the factor V and methylene
      tetrahydrofolate reductase genes. We believe that the combination of inherited
      and acquired hypercoagulable conditions affected her therapeutic response to
      anticoagulant therapy. Inherited thrombophilic DNA mutations may contribute to
      the hypercoagulability observed in patients with acquired thrombophilic
      conditions such as APS and systemic lupus erythematosus.

PMID- 11246681
TI  - Primary Sjogren's syndrome--treatment of fetal incomplete atrioventricular block
      with dexamethasone.
AB  - Pregnancies in women with autoantibodies against Ro/SSA and/or La/SSB may be
      associated with permanent and treatment resistant fetal atrioventricular (AV)
      block. We describe a patient with primary S ogren's syndrome and anti-Ro (60 kDa
      and 52 kDa) and anti-La autoantibodies, in whom fetal bradycardia with second
      degree AV block was detected at 19 + 0 weeks of gestation. Maternal treatment
      with dexamethasone (4 mg/day po) was started 2 days later. The baby's heart rate
      improved gradually, returning to normal after about 6 weeks of treatment. Our
      case illustrates the importance of close monitoring of the fetal heart rate in
      risk-pregnancies from about week 16 of gestation and initiation of dexamethasone
      treatment without delay when a block is detected.

PMID- 11246682
TI  - Minocycline induced autoimmune disease in rheumatoid arthritis: a missed
      diagnosis?
AB  - Minocycline is one of the major drugs for acne and is effective in rheumatoid
      arthritis (RA). We describe the first case of drug induced lupus secondary to the
      use of minocycline in a patient with RA. The dificulties of making this diagnosis
      as well as the implications for its pathogenesis are discussed.

PMID- 11246683
TI  - Corneal melt as the initial presentation of primary Sjogren's syndrome.
AB  - Corneal melting is a rare complication of S ogren's syndrome (SS). Previously
      reported cases of corneal ulceration occurred in patients with established SS,
      usually secondary to RA. We describe the first case of corneal ulceration with
      stromal melting as the initial presentation of primary SS. A 79-year-old man
      without prior sicca symptoms developed a large sterile corneal ulcer that
      required extensive treatment over several months with ocular lubricants, systemic
      immunosuppressives, and surgical repair. Evaluation for an underlying connective
      tissue disease revealed positive antinuclear antibodies (1:640 speckled) and anti
      SSA antibody. A lip biopsy established the diagnosis of SS. Ulceration later
      occurred in the contralateral eye. Two years after the last corneal ulcer and no
      longer taking prednisone, the patient's ocular disease remained quiescent taking
      azathioprine 175 mg and hydroxychloroquine 400 mg daily. This case highlights the
      potential for primary SS to present with serious ocular complications despite
      lack of a priori sicca symptoms, as well as the importance of immunosuppressive
      therapy in the treatment of this complication.

PMID- 11246684
TI  - Hypocomplementemic urticarial vasculitis, jaccoud's arthropathy, valvular heart
      disease, and reversible tracheal stenosis: a surfeit of syndromes.
AB  - We describe a patient who, during 29 years of observation, manifested
      polyarthralgia and polyarthritis leading to progressive deformity of the joints
      of hands and feet (without loss of cartilage or erosion of bone); persistent
      urticaria made worse by cold and accompanied by hypocomplementemia; and
      progressive cardiac valvular disease with mitral and aortic stenosis and
      regurgitation. In 1996, she developed subglottic tracheal stenosis that resolved
      by the end of 1997 without a change in treatment, which has consisted of low dose
      azathioprine, glucocorticoid, and nonsteroidal antiinflammatory drugs. Tests for
      cryoprecipitable protein, antineutrophil cytoplasmic antibodies, antinuclear
      antibody, and rheumatoid factor were negative. Skin biopsy was consistent with
      "leukocytoclastic vasculitis." The pathogenesis of this remarkable combination of
      syndromes is unknown.

PMID- 11246685
TI  - Selective involvement of the choroid plexus on cerebral magnetic resonance
      images: a new radiological sign in patients with systemic lupus erythematosus
      with neurological symptoms.
AB  - The selective involvement of the choroid plexus on brain magnetic resonance (MR)
      images is described in 2 patients with systemic lupus erythematosus presenting
      with neurological symptoms. The decrease in choroid plexus abnormalities on
      followup MR examination paralleled the clinical recovery with glucocorticoid
      therapy in both patients. Our cases indicate that selective involvement of the
      choroid plexus should be included in the spectrum of the radiological signs for
      neurological lupus.

PMID- 11246686
TI  - Characteristic marco- and microscopic aspect of the synovial membrane in crystal
      induced arthritis.

PMID- 11246687
TI  - Looking for important change/differences in studies of responsiveness. OMERACT
      MCID Working Group. Outcome Measures in Rheumatology. Minimal Clinically
      Important Difference.
AB  - The purpose of this paper is to describe a classification system for studies of
      responsiveness that was designed to help organize these studies, and identify
      those with the potential to provide information on minimal clinically important
      difference (MCID). We developed a 3 dimensional cube into which studies of
      responsiveness can be categorized based on their evaluation of 3 attributes: 1.
      individual or group setting; 2. which scores are contrasted; and 3. the type of
      change or difference being assessed. We present and discuss examples of studies
      that fit into categories in the classification cube. This classification system
      helps to focus attention on whether the literature is able to provide information
      on the specific type of change a person is interested in. It reinforces that the
      ability of an instrument to detect a certain category of discrimination within
      the cube does not mean it will necessarily be responsive to another category. The
      cube has been shown here as a means to separate out studies that address
      important change. These studies can then be examined as the source of information
      on MCID.

PMID- 11246688
TI  - Minimal clinically important differences: review of methods.
AB  - Determining a minimal clinically important difference to be detected in a
      clinical trial is a critical methodological step in the design of a study. In
      this review, the different methods that have been used in detecting important
      changes or differences are considered and categorized according to a
      classification system consisting of which groups are contrasted, the setting of
      the results, and the type of change of difference being quantified. It was found
      that most methods and procedures for deriving minimal clinically important
      differences considered important changes from the viewpoint of a group of
      patients. Development of methods that focus on individuals should be a goal of
      the future.

PMID- 11246689
TI  - Discrimination of changes in osteoporosis outcomes.
AB  - The purpose of this paper was to identify existing work related to
      discrimination, responsiveness, and minimal clinically important differences
      (MCID) for 4 key clinical outcomes in osteoporosis, to serve as a background to
      discussions about how to define MCID for both individuals and groups. The
      outcomes assessed were bone density, fractures, quality of life, and function. We
      conducted a systematic literature search in MEDLINE, EMBASE, and Current Contents
      for articles that discussed responsiveness, detectable difference, improvement
      criteria, and clinical importance. We used the Beaton cube to classify the
      studies depending on whether they compared differences between or changes within
      individuals or groups. Although a number of studies were identified that
      presented data on detectable differences beyond error and observed differences,
      few studies presented data on how to define clinically important differences. A
      key priority for future research is to define minimally clinical important
      differences for clinically important osteoporosis outcomes using a consensus
      based approach that will be accepted by the osteoporosis community at large.
      Furthermore, these MCID will likely be different for individual patients seen in
      clinical practice than for individuals in a clinical trial.

PMID- 11246690
TI  - A review of evidence on the discriminant validity of outcome measures in
      rheumatoid arthritis.
AB  - We have assessed the discriminant validity of functional status measures and
      measures that are part of the core set for rheumatoid arthritis. Papers were
      identified by a systematic literature search in MEDLINE and hand searching of
      references.

PMID- 11246691
TI  - Towards a definition of "difference" in osteoarthritis.
AB  - To assess existing information regarding detectable differences in osteoarthritis
      (OA), a systematic literature search was conducted up to December 1999. Thirty
      three articles were considered methodologically relevant to the definition and
      categorization of detectable differences in OA. It was determined that the
      musculoskeletal literature contains a wealth of information that relates to
      observed changes, much of which is derived from the clinical trials literature,
      but there have been relatively few methodological studies that have
      systematically evaluated the nature, categorization, and relevance of the change.
      Furthermore, most of those that have been published take the perspective of an
      individual or groups of experts other than that of the patient. This summary of
      the current literature reveals that the diverse sources of information go part
      way towards developing an understanding of detectable differences and their
      importance in the area of OA research and clinical practice. Stakeholders'
      interests as well as factors that modulate perceptions of importance need to be
      taken under consideration. In particular, the patient's perspective of the
      importance of change at an individual level requires further evaluation. This
      area of clinical research is relatively underdeveloped, but there is considerable
      opportunity for progress.

PMID- 11246692
TI  - Minimal clinically important difference. Low back pain: outcome measures.
AB  - A proposed standard "core set" of outcome measures for low back pain includes 5
      domains: back-specific function, generic health status, pain, work disability,
      and patient satisfaction. This paper focuses on the 2 recommended back-specific
      measures of function: the Roland-Morris Disability Questionnaire (RDQ) and the
      Oswestry Disability Index (ODI). We specifically address their ability to measure
      change. A systematic review of the literature identified a total of 78 and 71
      (RDQ and ODI, respectively) articles as potentially relevant. Detailed tables are
      provided for each citation, with the type of back pain population studied, the
      type of change measured, the estimate of change, and the interval over which the
      change was studied. These tables should be used as a reference for sample size
      calculation. The responsiveness of the RDQ found in the literature ranges from 2
      to 8 points on its 0 to 24 scale depending on what change is being measured. As a
      rough guide, Roland recommends that a change in 2-3 points on the RDQ should be
      considered the minimum clinically important change. Choosing any value larger
      than 5 in designing a clinical trial would risk underpowering the trial, since
      fewer patients are needed if a trial is designed on the basis of a large change
      score.

PMID- 11246693
TI  - Minimum clinically important difference: the crock of gold at the end of the
      rainbow?
AB  - The minimum clinically important difference (MCID), like the crock of gold at the
      end of the rainbow, is attractive but unattainable. Empirical data on how
      rheumatologists make clinical decisions show a wide variety of approaches and
      lack of agreement in decision making. Clinical importance needs to consider the
      magnitude of both the benefits and adverse events. A proposal for future attempts
      to define MCID could explore links between short term changes in outcomes to
      improvement in disability outcome many years later. Defining response to
      treatment could be explored using different approaches and involving patients and
      other professional groups.

PMID- 11246694
TI  - Individualized functional priority approach to the assessment of health related
      quality of life in rheumatology.
AB  - Over the past several years an interest has developed in health related quality
      of life questionnaires that address the specific concerns of each individual
      rather than the entire range of potential concerns for all patients. Even disease
      specific questionnaires do not capture the concerns of all individuals and some
      items in these questionnaires are irrelevant for a fairly large minority of
      people. This paper focuses on individualized functional priority questionnaires
      that allow patients to specify and prioritize their own personal disease related
      problems. Of particular interest are the scoring methods and responsiveness of
      these questionnaires, both necessary variables for defining minimal clinically
      important differences.

PMID- 11246695
TI  - Minimal clinically important difference module: summary, recommendations, and
      research agenda.

PMID- 11246696
TI  - IgG anti-beta2-glycoprotein I antibodies in adult patients with systemic lupus
      erythematosus.

PMID- 11246697
TI  - Epidemiologic and clinical features of Behcet's disease.

PMID- 11246698
TI  - Classification of chronic arthritides of childhood (juvenile idiopathic
      arthritis): criticisms and suggestions to improve the efficacy of the Santiago
      Durban criteria.

PMID- 11246699
TI  - Bone resorption and local interleukin-1alpha and interleukin-1beta synthesis
      induced by Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis
      lipopolysaccharide.
AB  - Different types of periodontopathic bacterial lipopolysaccharide (LPS) exert
      various biological activities in vitro. However, whether or not these activities
      also occur in vivo remains unclear. Thus the present study investigates bone
      resorption, as well as local IL-1alpha and IL-1beta synthesis induced by
      Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis LPS in the
      periodontal tissue of mice. Both types of LPS were injected into mouse gingiva
      every 48 h and the animals were sacrificed 6 h after the 1st. 4th, 7th, 10th,
      13th, 16th, 20th, or 24th injection. Bone resorption in the injected gingiva was
      histopathologically and histomorphometrically investigated and local
      concentrations of IL-1alpha and IL-1beta were detected using an enzyme-linked
      immunosorbent assay. The active resorption ratio was significantly higher in the
      group given the 10th injection of LPS from A. actinomycetemcomitans than in the
      group given P. gingivalis LPS. Furthermore, A. actinomycetemcomitans LPS
      stimulated significantly more synthesis of IL-1alpha than P. gingivalis LPS after
      the 4th and 10th injections. and of IL-1beta after the 4th, 7th, 10th, 13th, 16th
      and 20th injections. These results suggest that A. actinomycetemcomitans LPS is a
      more potent inducer of bone resorption and synthesis of IL-1alpha and IL-1beta in
      the short term than P. gingivalis LPS.

PMID- 11246700
TI  - Detection of putative periodontal pathogens in non-insulin-dependent diabetes
      mellitus and non-diabetes mellitus by polymerase chain reaction.
AB  - It has been assumed that there is a relationship between periodontal diseases and
      diabetes mellitus, however the putative periodontal microorganisms in non
      diabetes mellitus (non-DM) individuals and non-insulin-dependent diabetes
      mellitus (NIDDM) patients have not been well studied. In this study, the
      detection rates of 5 putative periodontal pathogens: Actinobacillus
      actinomycetemcomitans, Porphyromonas gingivalis, Eikenella corrodens, Treponema
      denticola, and Candida albicans by polymerase chain reaction (PCR) between NIDDM
      and non-DM adults were compared. A total of 246 adults were randomly recruited
      and periodontal parameters including: plaque index (P1I), gingival index (GI),
      probing depth (PD) and attachment level (AL) were recorded. Subgingival plaque
      samples were collected by sterile curettes from the most diseased and healthy
      sites based on PD and AL. The differences in periodontal parameters and
      microbiological data in healthy and diseased sites between non-DM and NIDDM
      patients were compared by chi-square analysis. The results showed no significant
      differences in age, gender, GI, P1I, PD, and prevalence of the 5 microorganisms
      between the NIDDM and the non-diabetic groups. However, except for A.
      actinomycetemcomitans, the prevalence of the periodontal microorganisms tested
      was significantly higher (p <0.001) in diseased sites than in the healthy sites
      in both groups. The P1I, GI, PD and AL were significantly higher in T. denticola
      positive sites than in negative sites. The results suggested that P. gingivalis,
      T. denticola, E. corrodens and C. albicans may play important roles in the
      periodontitis of both NIDDM and non-DM individuals, however the etiology of
      periodontitis in both groups may not be different from each other.

PMID- 11246701
TI  - Effect of lipopolysaccharide from periodontal pathogens on the production of
      tissue plasminogen activator and plasminogen activator inhibitor 2 by human
      gingival fibroblasts.
AB  - Both tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 2
      (PAI-2) are important proteolysis factors present in inflamed human periodontal
      tissues. The aim of the present study was to investigate the effect of
      lipopolysaccharide (LPS) on the synthesis of t-PA and PAI-2 by human gingival
      fibroblasts (HGF). LPS from different periodontal pathogens including
      Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Fusobacterium
      nucleatum were extracted by the hot phenol water method. The levels of t-PA and
      PAI-2 secreted into the cell culture media were measured by enzyme-linked
      immunosorbent assays (ELISA). The mRNA for t-PA and PAI-2 were measured by RT
      PCR. The results showed t-PA synthesis was increased in response to all types of
      LPS studied and PAI-2 level was increased by LPS from A. actinomycetemcomitans
      and F. nucleatum, but not P. gingivalis. When comparing the effects of LPS from
      non-periodontal bacteria (Escherichia coli and Salmonella enteritidis) with the
      LPS from periodontal pathogens, we found that the ratio of t-PA to PAI-2 was
      greater following exposure of the cells to LPS from periodontal pathogens. The
      highest ratio of t-PA to PAI-2 was found in those cells exposed to LPS from P.
      gingivalis. These results indicate that LPS derived from periodontal pathogens
      may cause unbalanced regulation of plasminogen activator and plasminogen
      activator inhibitor by HGF and such an effect may, in part, contribute to the
      destruction of periodontal connective tissue through dysregulated pericellular
      proteolysis.

PMID- 11246702
TI  - Nicotine effects on polymorphonuclear cell apoptosis and lipopolysaccharide
      induced monocyte functions. A possible role in periodontal disease?
AB  - Apoptosis provides a mechanism for clearance of unwanted cells in a variety of
      situations in which programmed or physiological cell death occurs; but the
      premature death of defensive cells could promote infection, inflammation and
      concomitant disease. We detected high values of apoptosis in polymorphonuclear
      cells (PMN) elicited from crevicular sulci of smokers affected by adult
      periodontitis. To learn more about the effects of nicotine on the periodontal
      environment, we studied its ability to modulate the apoptosis of two phagocytic
      lines, PMN and mononuclear cells, which are continuously recruited from gingival
      vessels to prevent or control plaque extension. Brief exposure of PMN to nicotine
      concentrations ranging from 0.01 to 0.3% shortened, in a dose-dependent
      relationship, the lag culture time required to observe at fluorescent microscopy
      the morphological traces of apoptosis. These observations were confirmed by
      specific tools of apoptosis: DNA fragmentation on gel electrophoresis and
      expression of the apoptosis-signaling receptor Fas/Apo-1. The apoptotic effect
      excited by nicotine on these first line defensive cells may be an important
      feature of the pathogenesis of periodontal disease. As for mononuclear
      leukocytes, nicotine was unable to induce apoptotic modifications on cells
      observed up to 72 h culture time, but the drug inhibited IL-1beta release and
      procoagulant activity (PCA) expression. The conflicting role played by these
      lipopolysaccharide (LPS)-induced monocyte functions in the inflammatory process
      is a further intrigue in the mechanism by which nicotine compromises the oral
      health.

PMID- 11246704
TI  - The dentogingival epithelial surface area revisited.
AB  - Recent studies implicating periodontitis as a cause of systemic diseases have
      reported that the surface area of periodontal pockets exposed to bacterial
      biofilm ranges from 50 cm2 to 200 cm2. Since the root surface area of the typical
      human dentition (excluding 3rd molars) is 75 cm2, these estimates appear too
      large. The goal of this study was to relate linear periodontal probing
      measurements to the dentogingival surface area (DGES). The DGES comprises both
      the sulcular and junctional epithelium, present in health, as well as any
      intervening pocket epithelium present in periodontitis. Formulas to estimate the
      DGES from clinical measures were derived from a meta-analysis of root surface
      areas, published values of root length, and a study that related the percent
      remaining root surface area to the percent remaining root length. These formulas
      were applied to a survey of the adult US population, the Veterans Affairs (VA)
      Dental Longitudinal Study, and a population of individuals visiting a
      periodontist. Individuals without periodontitis had a typical DGES of 5 cm2.
      Among individuals with periodontitis, the mean DGES in the three samples ranged
      from 8 cm2 (ranging from 1 cm2 to 29 cm2) to 20 cm2 (ranging from 2 cm2 to 44
      cm2). It was concluded that the mean DGES among individuals with periodontitis
      ranges from 8 cm2 to 20 cm2, considerably smaller than the range of 50 cm2 to 200
      cm2 currently assumed.

PMID- 11246703
TI  - Involvement of caspases in apoptotic cell death of murine macrophages infected
      with Actinobacillus actinomycetemcomitans.
AB  - Infection of murine macrophages in vitro with periodontopathic bacterium
      Actinobacillus actinomycetemcomitans induces apoptotic cell death. In this study,
      we investigated the involvement of caspases in apoptotic cell death of A.
      actinomycetemcomitans-infected macrophages. Two peptide inhibitors of caspases,
      benzyloxycarbonyl-Val-Ala-Asp (OMe)-fluoromethyl ketone (Z-VAD-FMK) and
      benzyloxycarbonyl-Asp-Glu-Val-Asp (OMe)-fluoromethyl ketone (Z-DEVD-FMK),
      inhibited apoptotic cell death of murine macrophage cell line J774.1 infected
      with A. actinomycetemcomitans. During the process of apoptosis, interleukin-1beta
      (IL-1beta) was detected in the culture supernatants of J774.1 cells. IL-1beta
      secretion was blocked by the caspase-1 inhibitor, Z-VAD-FMK, indicating that
      caspase-1 is involved in not only the induction of apoptosis but also the IL
      1beta secretion from A. actinomycetemcomitans-infected J774.1 cells. Immunoblot
      analysis revealed that the infection of A. actinomycetemcomitans to J774.1 cells
      induced the cleavage of retinoblastoma protein (Rb), suggesting that caspase-3
      was activated by A. actinomycetemcomitans infection. The cytosol from A.
      actinomycetemcomitans-infected J774.1 cells induced Rb proteolysis in vitro,
      which was inhibited by the caspase-3 inhibitor, Z-DEVD-FMK. Furthermore, caspase
      3-like activity was markedly increased in J774.1 cells infected with
      A.actinomycetemcomitans between 12 h and 24 h, which was subsequently inhibited
      by the addition of caspase-3 inhibitor, Z-DEVD-FMK. These findings indicate that
      caspase-3 induces apoptosis in J774.1 cells infected with A.
      actinomycetemcomitans. Taken together, these results suggest that caspase-1 and
      caspase-3 are involved in the induction of apoptosis in A. actinomycetemcomitans
      infected macrophages.

PMID- 11246705
TI  - Periodontal ligament cells secrete the factor that inhibits osteoclastic
      differentiation and function: the factor is osteoprotegerin/osteoclastogenesis
      inhibitory factor.
AB  - The periodontal ligament, a highly specialized connective tissue situated between
      the tooth and the alveolar bone of the tooth socket, has been thought to
      influence the remodeling of the alveolar bone. The effects of two human
      periodontal ligament fibroblastic cell populations (HPLFs) on osteoclast-like
      cell (OCL) formation and the function of authentic osteoclasts were examined. The
      addition of the conditioned media (CM) from both HPLF cultures (HPLF-CMs) to
      mouse bone marrow culture inhibited OCL formation in spite of the presence of 10(
      8)M 1alpha, 25 dihydroxyvitamin D3 (1alpha,25(OH)2D3). This inhibitory effect was
      most remarkable when both CMs were added during day 6 to day 9 following bone
      marrow culture, just at the late stage of OCL differentiation. HPLF-CMs also
      induced a significant decrease in the pit area and the pit number formed by
      authentic osteoclasts on ivory slices. The administration of neutralizing
      monoclonal antibody (OI-1) against human osteoprotegerin (OPG)/osteoclastogenesis
      inhibitory factor (OCIF) with HPLF-CMs to mouse bone marrow culture almost
      completely blocked the inhibitory effect of these CMs on OCL formation.
      Immunofluorescent examination of HPLF with OI-1 revealed intense positive
      reactivity in the cytoplasm. Western blot analysis of HPLF-CM using anti-human
      OPG/OCIF polyclonal antibody resulted in the detection of bands of 60 kDa and 120
      kDa which were consistent with those of OPG/OCIF. These results suggest that HPLF
      cells produce and secrete OPG/OCIF, and that this factor from HPLF prevents the
      differentiation of the late preosteoclast and the function of the mature
      osteoclasts.

PMID- 11246706
TI  - Occlusal hypofunction causes changes of proteoglycan content in the rat
      periodontal ligament.
AB  - The biological functions of proteoglycans and glycosaminoglycans are closely
      associated with mechanical stress on the tissue. In order to reveal the
      relationship between proteoglycans in the periodontal ligament and mechanical
      stress such as occlusal stimuli, occlusal hypofunction of rat unilateral
      mandibular molars was induced by extraction of the opposing first, second and
      third maxillary molars. Immunohistochemical analyses were performed using
      antibodies for chondroitin sulfate, decorin, biglycan, heparan sulfate and
      keratan sulfate, and hyaluronic acid-binding protein. Chondroitin sulfate,
      observed more strongly in the cervical side than in the apical side of the
      periodontal ligament of the unextracted sides of mandible, and uniformly present
      in the extracellular matrix of the periodontal ligament, decreased significantly
      from 1 wk post-extraction of the antagonists, with a decrease in thickness and
      disarrangement in fibrous components. Decorin core protein, uniformly present in
      the periodontal ligament of the unextracted sides, decreased as early on as 2 d
      post-extraction. Heparan sulfate, mainly localized on the cell surface of
      vascular endothelial cells and osteoclastic cells as well as in the extracellular
      matrix of the unextracted sides, decreased significantly in association with the
      decreased number of blood vessels and osteoclastic cells as early on as 2 d post
      extraction. Biglycan, keratan sulfate and hyaluronic acid, uniformly distributed
      in the periodontal ligament of the unextracted sides, showed little change after
      the extraction. These results demonstrate that occlusal hypofunction causes
      tissue remodeling of the periodontal ligament, with a significant decrease of
      chondroitin sulfate, decorin and heparan sulfate.

PMID- 11246707
TI  - American Academy of Allergy, Asthma and Immunology 57th Annual Meeting. March 16
      21, 2001. Abstracts.

PMID- 11246708
TI  - Introduction to the special issue on behavioral phenotypes.

PMID- 11246709
TI  - Variability in FMRP and early development in males with fragile X syndrome.
AB  - To test the hypothesis that variability in development in fragile X syndrome is
      related to FMRP (the protein deficient in this syndrome expression), we studied
      53 males between 23 and 98 months of age. For the entire group, which included
      males with either mosaism, partially methylated full mutation, and fully
      methylated full mutation, FMRP expression ranged from 1% to 40% and accounted for
      a small but significant amount of variance in level, but not rate, of total
      development as well as motor, social, adaptive, cognitive, and language
      development. For males with a fully methylated full mutation, the association was
      in the hypothesized direction, but not statistically significant. Findings
      support the hypothesized relationship between FMRP and individual capabilities
      but suggest that other factors also play a major role.

PMID- 11246710
TI  - Conversational characteristics of children with fragile X syndrome: repetitive
      speech.
AB  - The production of repetitive speech during conversations was studied in people
      with fragile X syndrome, autistic disorder, or mental retardation not caused by
      fragile X. Repetitive speech was found to be more prevalent among those with
      fragile X compared to the control groups, especially within atypical utterances.
      These results suggest that the repetitive speech seen in individuals with fragile
      X is not the result of either general developmental delay or undiagnosed autistic
      disorder, and they support our hypothesis that such speech dysfluency reflects
      the effects of physiological arousal caused by hypersensitivity to social and
      sensory stimuli. Our results are interpreted within Perkins' theory of
      neuropsycholinguistic function.

PMID- 11246711
TI  - Emergence of compulsive behavior and tantrums in children with Prader-Willi
      syndrome.
AB  - Many adults with Prader-Willi syndrome are affected by behaviors such as
      tantrums, skin-picking, and compulsions. The nature and extent of these problems
      suggest more attention be directed to their emergence in childhood. Our purpose
      was to investigate behavior problems in children with this syndrome and identify
      the age at which these behaviors emerge. Parents of children with Prader-Willi
      syndrome, Down syndrome, and those developing typically completed questionnaires.
      Children with Prader-Willi syndrome exhibited more compulsions, skin-picking, and
      tantrums than did the other groups. A discriminant analysis of behavior variables
      derived two statistically significant functions that were interpreted as
      developmental milestones and problematic behavior. These functions correctly
      predicted membership for 79% of grouped cases.

PMID- 11246712
TI  - Strengthening behavioral research on genetic mental retardation syndromes.
AB  - In this article we examine the status of behavioral research on genetic mental
      retardation syndromes. Although surveys suggest increased interest in such
      research, the field continues to struggle with three methodological issues: (a)
      how to think about control or contrast groups, (b) the interplay of behavioral
      phenotypes with development and other factors relating to within-group variation,
      and (c) the efficacy of etiology-based interventions. For each issue, we discuss
      salient concerns and make suggestions for future work.

PMID- 11246713
TI  - Characterization of self-injurious behaviors in children and adults with Smith
      Magenis syndrome.
AB  - A characteristic pattern of stereotypic and self-injurious behavior (SIB)
      distinguishes Smith-Magenis syndrome from many other genetic disorders. We
      examined the prevalence and severity of 11 specific types of SIB in 29 children
      and adults with Smith-Magenis syndrome. We confirmed the near universal presence
      of SIB in people with this disorder. The overall prevalence of SIB was found to
      increase with age as was the number of different types of SIB demonstrated by
      individuals with Smith-Magenis syndrome. The number of different types of SIB
      exhibited was also directly correlated with level of intellectual functioning.
      Our data suggest that with increasing age and ability levels, people with Smith
      Magenis syndrome add to their repertoire of SIB from among a small number of
      specific behaviors.

PMID- 11246714
TI  - Emotion recognition by children with Down syndrome.
AB  - In three studies, children with Down syndrome were presented with emotion
      recognition tasks designed to tap their knowledge of simple emotions, their
      ability to label emotions, and their understanding of emotions from simple, story
      based contexts. Results indicate that young children with Down syndrome perform
      similarly to typical controls matched on MAs of approximately 3 years. However,
      by developmental age of 4 years, children with Down syndrome performed worse than
      both MA-matched typical children and children with non-Down syndrome types of
      mental retardation. Although the MAs of children with Down syndrome increased
      over 2-years, their emotion recognition abilities did not. Taken together,
      findings suggest both etiological and developmental differences in the emotion
      recognition abilities of children with Down syndrome.

PMID- 11246715
TI  - Longitudinal course of behavioral and emotional problems in Williams syndrome.
AB  - A follow-up study of behavior and emotional problems in a cohort of young people
      with Williams syndrome 5 years after first assessment is described. Using a
      between-/within-subjects factorial layout, we compared scores on the
      Developmental Behaviour Checklist between young people with Williams syndrome and
      a large epidemiological control sample of young people with mental retardation
      due to other causes from Time 1 (1990/1991) to Time 2 (1995/1996). Results showed
      substantial persistence of the overall level of behavior and emotional problems.
      However, there were changes in certain types of behavior. Participants with
      Williams syndrome had significantly higher overall behavioral and emotional
      problems, communication disturbance, and anxiety over the 5-year period. Further,
      10 or 13 checklist items maintained significantly higher levels among the
      Williams syndrome sample.

PMID- 11246716
TI  - Adaptive behavior of 4- through 8-year-old children with Williams syndrome.
AB  - The adaptive behavior of forty-one 4- through 8-year-olds with Williams syndrome
      was assessed using the Vineland Adaptive Behavior Scales-Interview Edition. Based
      on the cognitive and personality profiles characteristic of children with this
      syndrome, we predicted that the domains of Socialization and Communication would
      be relative strengths, whereas Daily Living Skills and Motor Skills would be
      relative weaknesses. We also expected that Socialization Skills would be more
      advanced than Communication skills, and that within the Socialization domain,
      interpersonal skills would be stronger than play/leisure or coping skills. All
      predictions were confirmed. Adaptive behavior standard score was not related to
      CA. The children earned similar overall standard scores on the Vineland and the
      Differential Ability Scales. Interrelations among adaptive behavior, cognitive
      abilities, and personality characteristics are discussed.

PMID- 11246718
TI  - 2001 Annual Meeting of the American Society for Clinical Pharmacology and
      Therapeutics. Orlando, Florida, USA. March 6-10, 2001. Abstracts.

PMID- 11246717
TI  - Drawings by individuals with Williams syndrome: are people different from shapes?
AB  - Because it is unclear whether people with Williams syndrome produce drawings that
      are delayed or deviant, we examined these two possibilities in Draw a Person and
      figure copying tasks (VMI) in 28 persons with Williams syndrome, 28 with mixed
      etiologies, and 28 with Down syndrome. All human figures could be classified into
      discrete stages of drawing development, and in all groups, drawing tasks were
      significantly correlated with MA. Human figures from participants with Williams
      syndrome were no more deviant than their counterparts, nor did they show "local
      global" differences. Draw a Person scores exceeded VMI scores in the Williams
      syndrome group, whereas the Down syndrome group showed relative strengths on both
      drawing tasks, and the mixed group had no profile. Developmental and phenotypic
      implications of findings are discussed.

PMID- 11246719
TI  - The war on addiction.

PMID- 11246720
TI  - How it all starts inside your brain.

PMID- 11246721
TI  - New ways to stay clean.

PMID- 11246722
TI  - Rethinking zero tolerance.

PMID- 11246723
TI  - Can this pill stop you from hitting the bottle?

PMID- 11246724
TI  - The war on drugs goes to the air.

PMID- 11246725
TI  - Robert Downey Jr., takes one day at a time.

PMID- 11246726
TI  - 'The enemy is every one of us'.

PMID- 11246727
TI  - Full stem ahead.

PMID- 11246728
TI  - Building blocks for every kid.

PMID- 11246730
TI  - Chemotherapy agents in transitional cell carcinoma: the old and the new.
AB  - Transitional cell carcinoma is a malignancy in which a number of single agents
      with different mechanisms of action are effective. Most older agents have limited
      activity, but several combinations are quite active. The most common regimens
      over the past 15 years were cyclophosphamide, doxorubicin, and cisplatin (CAP,
      CISCA); cisplatin, methotrexate, and vinblastine (CMV, MCV); and (methotrexate,
      vinblastine, doxorubicin, and cisplatin (M-VAC). Several new agents have been
      identified recently, including docetaxel, paclitaxel, gemcitabine, and
      ifosfamide. Combinations using these new agents now provide alternatives to the M
      VAC combination that have much less toxicity and, in some instances, are used as
      multimodality therapy in patients with unresectable primary tumors without the
      degree of toxicity associated with older combinations of chemotherapy. Phase II
      and Phase III trials evaluating these new combinations are reviewed.

PMID- 11246729
TI  - Life after cystectomy and orthotopic neobladder versus ileal conduit urinary
      diversion.
AB  - Patients frequently complain about changes in their everyday life after radical
      cystectomy and urinary diversion. The aim of this study was to compare subjective
      morbidity of ileal neobladder to the urethra versus ileal conduit urinary
      diversion and to elucidate its influence on quality of life. A total of 102
      patients who underwent radical cystectomy due to a bladder malignancy were
      included in the study: 69 patients (67.6%) with an orthotopic neobladder and 33
      patients (32.4%) with an ileal conduit. The compliance was 99% and mean follow-up
      was 37 months. All patients completed two retrospective quality-of-life
      questionnaires, namely the QLQ-C30 and a questionnaire developed at our
      institution to elucidate specific items regarding urinary diversion. The
      questioning was performed by a nonurologist. The results obtained from the
      validated (QLQ-C30) and our self-designed questionnaire clearly demonstrate that
      patients with an orthotopic neobladder better adapt to the new situation than
      patients with an ileal conduit. In addition, neobladder to the urethra improves
      quality of life due to a better self-confidence, better rehabilitation as well as
      restoration of leisure, professional, traveling, and social activities, and
      reduced risk of inadvertent loss of urine. For example, 74.6% of neobladder
      patients felt absolutely safe with the urinary diversion in contrast to 33.3% in
      the ileal conduit group. Only 1.5% of neobladder patients had wet clothes caused
      by urine leakage during day versus 48.5% of ileal conduit patients; 92.8% of
      neobladder patients felt not handicapped at all; and 87% felt not sickly or ill
      in contrast to 51.5% and 66.7% of ileal conduit patients, respectively. Moreover,
      97% of our neobladder patients would recommend the same urinary diversion to a
      friend suffering from the same disease in contrast to only 36% of ileal conduit
      patients. The results obtained by this study demonstrate that quality of life is
      preserved in a higher degree after orthotopic neobladder than after ileal conduit
      urinary diversion.

PMID- 11246731
TI  - Rebuilding the lower urinary tract after cystectomy: a roadmap for patient
      selection and counseling.
AB  - Numerous options exist for reconstructing the lower urinary tract after radical
      cystectomy. Deciding between continent and noncontinent urinary diversion can be
      challenging for both physician and patient. This process should be logical and
      should integrate factors including the patient's malignancy, comorbid disease,
      functional status, and personal preference. Thorough patient education and a
      delicate balance between risk and benefit are critical to the success of any
      strategy for urinary diversion. This review presents a basic algorithm for
      planning reconstructive options and counseling patients before cystectomy.

PMID- 11246732
TI  - Indications for urethrectomy.
AB  - This review article addresses the pertinent issues regarding management of the
      urethra in the setting of transitional cell carcinoma of the bladder. This topic
      is often a subject of considerable confusion among urologic surgeons and is
      timely in this era of routine orthotopic diversion. The risk of urethral
      recurrence in the retained urethra is approximately 10%. Of the potential risk
      factors that may predispose the retained anterior urethra to metachronous
      transitional cell carcinoma, involvement of the prostatic urethra, glands, or
      stroma is the most significant. In this circumstance, if a cutaneous diversion is
      performed, urethrectomy is indicated. Conversely, for orthotopic diversion,
      involvement of the prostatic urethra with transitional cell carcinoma is not a
      contraindication to proceeding. Orthotopic diversion should be aborted, and
      cutaneous diversion and urethrectomy should be performed, only if intraoperative
      frozen section of the prostatic urethra margin is positive. In a woman, en bloc
      urethrectomy should be included with cystectomy if cutaneous diversion is
      planned. Although tumor involvement of the female bladder neck is a risk factor
      for urethral disease, prospective studies suggest that intraoperative frozen
      section evaluation of the proximal urethra is more accurate and can be used to
      exclude orthotopic diversion at cystectomy. Using these and other guidelines,
      management of the urethra should be straightforward and less concerning for the
      urologic surgeon.

PMID- 11246733
TI  - Pelvic recurrences post cystectomy: current treatment strategies.
AB  - Pelvic recurrence following cystectomy is a devastating problem for both
      physician and patient. Patients who recur locally usually do so within the first
      2 years following surgery. Stage, grade, and possibly p53 status of the tumor are
      prognostic indicators for local failure. Patients with extensive disease at the
      time of diagnosis may benefit from adjuvant or neoadjuvant treatment to attempt
      to decrease the rate of recurrence. Treatment of patients with local failure
      should use a multimodality approach that includes systemic chemotherapy with or
      without local radiation therapy or surgery. Although rare, long-term survival can
      be achieved in selected patients.

PMID- 11246734
TI  - Cystectomy in the elderly.
AB  - Invasive bladder cancer is a disease of the elderly. With the elderly population
      rapidly growing and living longer than ever before, a larger number of patients
      75 years of age or older will develop invasive bladder cancer. Currently
      available data indicate that well-selected elderly patients, even those 80 years
      old or older, do not have a significantly higher risk of morbidity or mortality
      from cystectomy than do younger patients. Cystectomy in patients of advanced age
      requires a multidisciplinary team approach and increased vigilance in the
      perioperative period but can be performed safely. Most elderly patients diagnosed
      with invasive bladder cancer, if left untreated by cystectomy, will die of the
      disease and not from competing age-related illness. Therefore, radical cystectomy
      should not be withheld from elderly patients on the basis of age alone.

PMID- 11246735
TI  - Quality of life with reconstruction.
AB  - Quality-of-life considerations were one of the main driving forces behind the
      development of continent urinary diversion. However, the field of formal quality
      of-life study that allows us to document these aspects of treatment is still
      relatively young. In the past decade, a number of quality-of-life studies of
      cystectomy patients have been undertaken, with somewhat mixed results. Many of
      these studies have been limited by small patient numbers, and the differences in
      the various treatment groups, for example, in age and comorbidities. Most have
      shown that overall quality of life after cystectomy remains good for most
      patients, with the expected problems with urinary diversion and sexual
      dysfunction. However, few differences between the diversion groups have been
      demonstrated, suggesting that patients adapt to whatever is required of them. One
      large study from Germany did find significant improvement in several aspects of
      quality of life in patients with continent diversion. Patient education,
      exploration of the pros and cons of the various alternatives, and active patient
      participation in the treatment decisions seem to be key to postoperative
      satisfaction.

PMID- 11246736
TI  - Randomized trials of adjuvant and neoadjuvant chemotherapy in bladder cancer.
AB  - Data of randomized studies of adjuvant and neoadjuvant chemotherapy for patients
      with muscle-invasive bladder cancer were reviewed. Four adjuvant studies have
      been published. The interpretation of their data is compromised primarily because
      of small patient numbers. Thus, a possible survival advantage cannot be
      documented, and significantly larger, prospective studies are needed. However,
      there is some evidence of improved disease-free survival for patients with non
      organ-confined tumors treated with cisplatin-based combination chemotherapy. More
      data are available for neoadjuvant chemotherapy. The already published randomized
      studies, including a large trial of who was designed to detect a 10% survival
      benefit, do not indicate a significant advantage for neoadjuvant chemotherapy.
      Radical cystectomy remains the standard treatment to which other therapeutic
      modalities must be compared.

PMID- 11246737
TI  - The National Bladder Cancer Group's experience: invasive and metastatic bladder
      cancer selected reports.
AB  - The National Bladder Cancer Group, a multidisciplinary organization that was
      originally the therapeutic arm of the National Bladder Cancer Project, reported
      the results of trials using cisplatin with and without cyclophosphamide in
      patients with advanced bladder cancer. The objective response rate in both arms
      was 16% of 109 patients with no difference between the arms. Other studies
      included cisplatin and irradiation for patients who had comorbid conditions that
      prevented cystectomy (local response--cT2 11/13 patients; cT3 & cT4 2/4
      patients). Seventy patients were treated on the same protocol, and 33 were alive
      4 years later. Complete response versus local failure produced 57% versus 11% at
      4 years. After cessation of funding, the clinicians at the Massachusetts General
      Hospital agreed to follow a potentially bladder-sparing multimodality protocol,
      which stipulated that visible tumor be resected following which the patient
      received methotrexate, vinblastine and cisplatin (MCV), small-volume irradiation,
      and more cisplatin with midcourse cystectomy if local tumor persisted. Overall
      survival was 45%. The Radiation Therapy Oncology Group conducted a similar study
      omitting MCV from one arm. The 5-year survival rate was 38% with no advantage for
      either arm.

PMID- 11246738
TI  - The Nordic experience of cooperative urinary bladder cancer trials.
AB  - The Nordic Urological Association Urothelial Group has been organizing phase 3
      trials in urinary bladder cancer therapy since 1986. In total, around 1,000
      patients from three countries have entered these studies. The results of the
      different trials are reviewed, and the problems with cooperative trials are
      discussed. The importance of these kind of trials in setting up management
      guidelines is underscored.

PMID- 11246739
TI  - VI--choosing the right reconstruction for your female patients.
AB  - Like in male patients, selection of female patients for an orthotopic neobladder
      is important from an oncological and functional standpoint. The anatomy and the
      behavior of the isolated urethra in women had to be restudied because of the
      shorter urethra, the absence of the prostate, an undefined level of urethral
      dissection, and the different anatomy of the urethral sphincter-system.
      Retrospective long-term observations of female patients with primary bladder
      cancer revealed a 2% incidence of secondary urethral tumors in women. The only
      significant risk factor for urethral tumor involvement was primary bladder cancer
      at the bladder neck. Any type of gastrointestinal segment may be used for
      creating a pouch in women. As a result of an approximately 15% possibility of
      urinary retention or larger post-void residuals, the use of an efficient
      antireflux valve mechanism seems prudent. Clinical experience in an increasing
      number of women confirms the preliminary favorable results. Despite the selection
      criteria outlined in this article, most women can safely and rewardingly be
      offered an orthotopic neobladder.

PMID- 11246740
TI  - A case of Standford type B aortic dissection involving a right-sided aortic arch
      with mirror-image branching and right-sided descending aorta.
AB  - Isolated right aortic arch with mirror-image branching is a rare congenital
      anomaly. To date, no case has been reported for aortic dissection involving a
      right aortic arch with mirror-image branching. We report here on a case involving
      a 58-year-old man in whom expanding type B aortic dissection was demonstrated in
      the right aortic arch with mirror-image branching and a right descending aorta.
      The patient was successfully treated by interposition of a prosthetic graft via a
      right posterolateral thoracotomy approach. We also reviewed the literature.

PMID- 11246741
TI  - Coupling of inflammatory cytokine signaling pathways probed by measurements of
      extracellular acidification rate.
AB  - There is a growing interest in the mechanisms of how cells integrate the
      multitude of signals that emanate during inflammatory stimuli, such as the
      hepatic acute phase response to burn or trauma. We have used measurements of
      extracellular acidification rate (ECAR) of HepG2 cells cultured on microporous
      membranes to probe the coupling between signaling pathways for gp130 family
      cytokines (interleukin-6, oncostatin M) and IL-1, each of which is considered to
      play a significant role in the hepatic acute phase response. We found that brief
      (30 min or less) exposure to any of these cytokines desensitized the HepG2 cells
      to subsequent exposure with the same cytokine. Furthermore, we found that this
      property serves as a probe of the coupling of signaling pathways: exposure to IL
      1 did not desensitize the cells to exposure to OSM and vice versa. However, cells
      exposed to IL-6 with soluble gp80, which together share with OSM the use of gp130
      as a signal transducing receptor, were subsequently unable to respond to OSM, and
      vice versa. Simultaneous exposure of cells to moderate concentrations (near their
      respective EC50 values) of both IL-1 and OSM resulted in synergistic effects on
      the ECAR, but simultaneous exposure to saturating concentrations of IL-1 and OSM
      resulted in a response that tracked that of OSM alone. These results suggest that
      the signaling pathways of IL-1 and OSM may be simultaneously activated in HepG2
      cells under moderate inflammatory cytokine challenge but that the cells must
      prioritize their response under extreme cytokine challenges.

PMID- 11246742
TI  - Re-evaluation of osmotic effects as a general adaptative strategy for bacteria in
      sub-freezing conditions.
AB  - We studied the molecular mechanisms of adaptation of a Siberian psychrophilic
      bacterial strain. Upon adaptation to 4 degreesC from 24 degreesC, the major
      changes observed were in the membrane and cell surface chemistry. There was no
      evidence for the formation of so-called 'compatible metabolites' that are thought
      to be responsible for the survival at very low to sub-freezing temperatures. The
      membrane fatty acids were shorter with an increased amount of unsaturation in the
      4 degreesC cells compared to the 24 degreesC cells. The absence of a significant
      amount of phosphorylation in the membrane lipids at 4 degreesC compared to the
      levels at 24 degreesC was another significant difference. At 4 degreesC, the cell
      size was reduced in volume by a factor of approximately 14 compared to its size
      at 24 degreesC. The polar polysaccharide capsular layer was also significantly
      reduced. There were no significant changes in the protein profiles indicating
      that antifreeze proteins were not being produced. The results obtained here are
      consistent with observations and established theories and principles on and about
      the behavior of water in confined spaces. These indicate that ordering effects,
      surface charge and polarity are the key determinants of the freezing point and
      the type of ice structure that will be formed when water is confined to an area
      of the size of a bacterial cell.

PMID- 11246743
TI  - Conformation transition kinetics of regenerated Bombyx mori silk fibroin membrane
      monitored by time-resolved FTIR spectroscopy.
AB  - The ethanol-induced conformation transition of regenerated Bombyx mori silk
      fibroin membrane from a poorly defined to the well ordered state was monitored by
      time-resolved Fourier transform infrared spectroscopy (FTIR) for the first time.
      From the analysis of FTIR difference spectra, taken on time scales as short as 6
      s and up to 1 h after addition of ethanol, intensity vs. time plots of an
      increasing band at 1618 cm(-1) were observed indicating formation of a beta-sheet
      coincident with the loss of intensity of a band at 1668 cm(-1) indicating
      decreases of random coil and/or silk I structure. Both infrared markers were
      fitted with identical biphasic exponential decay functions, however, there was a
      clear burst phase occurring prior to the onset of the observed transitions. The
      conformation transition process is indicated to either proceed sequentially
      through (at least) two intermediate states that contain different levels of beta
      sheet structure or to have parallel pathways of initial beta-sheet formation
      followed by a slower 'perfection' phase. The first observed process forms in a
      burst phase a few seconds after mixing (or even faster), prior to the collection
      of the first spectrum at 6 s. The second observed process occurs with a time
      constant of approximately 0.5 min, the intermediate present at this stage then
      continues with a time constant of 5.5 min completing the observed formation of
      the beta-sheet. The conformation transition of this slower intermediate is not
      only indicated by an analysis of the kinetics of the random coil and beta-sheet
      specific bands discussed above, it roughly coincides with the appearance of an
      additional infrared marker at 1695 cm(-1), which may be a marker for beta-sheet
      structure specific to the formation of the perfected structure. The conformation
      transition of this protein analyzed by infrared spectroscopy provides insight
      into a part of the fascinating process of cocoon formation in B. mori.

PMID- 11246744
TI  - Intracellular Mg2+ diffusion within isolated rat skeletal muscle fibers.
AB  - Intracellular free magnesium concentration ([Mg2+]i) was measured in
      enzymatically isolated rat skeletal muscle fibers using the fluorescent dye mag
      indo-1. The change in [Mg2+]i produced by a local intracellular microinjection of
      magnesium pidolate (magnesium pyrrolidone carboxylate) was measured at a given
      distance from the injection site. In one series of experiments this protocol was
      tested on isolated fibers that were completely embedded into silicone grease:
      under these conditions, the injection produced an increase in [Mg2+]i that
      reached a steady level some time following the injection. The time-course of the
      [Mg2+]i change could be well accounted for by a model of longitudinal diffusion.
      The mean apparent Mg2+ diffusion coefficient (D(app)) was 188+/-9 microm2 s(-1)
      (n = 16), approximately four times lower than the value measured in vitro. This
      reduction likely results from the effects of cytoplasmic viscosity and of Mg2+
      binding to low affinity static sites. Another series of measurements was
      performed on fibers that were either partially or completely free of silicone:
      under these conditions, the time course of the change in [Mg2+]i was in many
      cases more complex than predicted by simple diffusion.

PMID- 11246745
TI  - Binding of small alcohols to a lipid bilayer membrane: does the partitioning
      coefficient express the net affinity?
AB  - The total vapor pressures at 26 degreesC of binary (water-alcohol) and ternary
      (water-alcohol-vesicle) systems were measured for six short chain alcohols. The
      vesicles were unilamellar dipalmitoyl phosphatidylcholine (DMPC). The data was
      used to evaluate the effect of vesicles on the chemical potential of alcohols
      expressed as the preferential binding parameter of the alcohol-lipid interaction,
      gamma23. This quantity is a thermodynamic (model-free) measure of the net
      strength of membrane-alcohol interactions. For the smaller investigated alcohols
      (methanol, ethanol and 1-propanol) gamma23 was negative. This is indicative of so
      called preferential hydration, a condition where the affinity of the membrane for
      water is higher than the affinity for the alcohol. For the longer alcohols (1
      butanol, 1-pentanol, 1-hexanol) gamma23 was positive and increasing with
      increasing chain length. This demonstrates preferential binding, i.e. enrichment
      of alcohol in the membrane and a concomitant depletion of the solute in the
      aqueous bulk. The measured values of gamma23 were compared to the number of
      alcohol-membrane contacts specified by partitioning coefficients from the
      literature. It was found that for the small alcohols the number of alcohol
      membrane contacts is much larger than the number of preferentially bound solutes.
      This discrepancy, which is theoretically expected in cases of very weak binding,
      becomes less pronounced with increasing alcohol chain length, and when the
      partitioning coefficient exceeds approximately 3 on the molal scale (10(2) in
      mole fraction units) it vanishes. Based on this, relationships between structural
      and thermodynamic interpretations of membrane partitioning are discussed.

PMID- 11246746
TI  - Lens crystallins and oxidation: the special case of gammaS.
AB  - Among lens crystallins, gamma-crystallins are particularly sensitive to
      oxidation, because of their high amount of Cys and Met residues. They have the
      reputation to induce, upon ageing, lens structural modifications leading to
      opacities. A combination of small angle X-ray scattering and chromatography was
      used to study the oxidation of gamma-crystallins. At pH 7.0, all the gamma
      crystallins under study were checked to have the same structure in solution.
      Under gentle oxidation conditions at pH 8.0, human gammaS (hgammaS) and bovine
      gammaS (bgammaS) formed disulfide-linked dimers, whereas the other bgamma
      crystallins did not. Cys20 was shown to be responsible for dimer formation since
      the C20S mutant only formed monomers. The hgammaS dimers were stable for weeks
      and did not form higher oligomers. In contrast, monomeric gammaS-crystallins
      freshly prepared at pH 8.0, and submitted to more drastic oxidation by X-ray
      induced free radicals, were rapidly transformed into higher oligomers. So, only
      extensive oxidation causing partial unfolding could be detrimental to the lens
      and linked to cataract formation. The gammaS-crystallins lack the temperature
      induced opacification observed with the other gamma-crystallins and known as cold
      cataract. The oxidation-induced associative behaviour and cold cataract are
      therefore demonstrated to be uncoupled.

PMID- 11246747
TI  - No effect of trimethylamine N-oxide on the internal dynamics of the protein
      native fold.
AB  - Trimethylamine N-oxide (TMAO) is a natural osmolyte accumulated in cells of
      organisms as they adapt to environmental stresses. In vitro, TMAO increases
      protein stability and forces partially unfolded structures to refold. Its effects
      on the native fold are unknown. To investigate the interrelationship between
      protein stability, internal dynamics and function, the influence of TMAO on the
      flexibility of the native fold was examined with four different proteins by Trp
      phosphorescence spectroscopy. Its influence on conformational dynamics was
      assessed by both the intrinsic phosphorescence lifetime, which reports on the
      local structure about the triplet probe, and the acrylamide bimolecular quenching
      rate constant that is a measure of the average acrylamide diffusion coefficient
      through the macromolecule. The results demonstrate that for apoazurin, alcohol
      dehydrogenase, alkaline phosphatase and glyceraldehydes-3-phosphate dehydrogenase
      1.8 M TMAO does not perturb the flexibility of these macromolecules in a
      temperature range between - 10 degreesC and up to near the melting temperature.
      This unexpected finding contrasts with the dampening effect observed with polyols
      as well as with the expectations based on the preferential exclusion of the
      osmolyte from the protein surface.

PMID- 11246748
TI  - In-situ FTIR study on adsorption and oxidation of native and thermally denatured
      calf thymus DNA at glassy carbon electrodes.
AB  - In-situ Fourier transform infra-red (FTIR) spectra of native and thermally
      denatured calf thymus DNA (CT DNA) adsorbed and/or oxidized at a glassy carbon
      (GC) electrode surface are reported. The adsorption of native DNA occurs
      throughout the potential range (- 0.2 approximately 1.3 V) studied, and the
      adsorbing state of DNA at electrode surface is changed from through the C=O band
      of bases and pyrimidine rings to through the C=O of cytosine and imidazole rings
      while the potential shifts negatively from 1.3 V to -0.2 V. An in-situ FTIR
      spectrum of native CT DNA adsorbed at GC electrode surface is similar to that of
      the dissolved DNA, indicating that the structure of CT DNA is not distorted while
      it is adsorbed at the GC electrode surface. In the potential range of -0.2
      approximately1.30 V, the temperature-denatured CT DNA is adsorbed at the
      electrode surface first, then undergoes electrochemical oxidation reaction and
      following that, diffuses away from the electrode surface.

PMID- 11246751
TI  - Electrical systems in medical locations.

PMID- 11246752
TI  - Biting on sandwich issues.

PMID- 11246750
TI  - Cumulative author and subject index for volumes 173-183.

PMID- 11246749
TI  - Fluctuations in sliding motion generated by independent and random actions of
      protein motors.
AB  - We consider theoretical fluctuations in the in vitro sliding movement of
      individual cytoskeletal filaments generated by an ensemble of protein motors
      whose actions are assumed to be statistically independent and random. We show
      that the mean square deviation of the sliding distances of a filament for a given
      period of time around their average is proportional to the inverse of the
      filament length. This result provides a basis for an experimental test of the
      general assumption on the independent and random actions of protein motors.

PMID- 11246753
TI  - Mortuaries: issues of safety.

PMID- 11246754
TI  - Office humidity must be monitored.

PMID- 11246755
TI  - The heavyweights.

PMID- 11246756
TI  - 100 top hospitals. Orthopedic benchmarks.

PMID- 11246758
TI  - 100 top hospitals. ICU benchmarks.

PMID- 11246757
TI  - 100 top hospitals. Stroke benchmarks.

PMID- 11246759
TI  - 100 top hospitals. Cardiovascular benchmarks.

PMID- 11246760
TI  - 100 top hospitals. Clinical research program.

PMID- 11246761
TI  - Best at 100 top. Breast cancer management.

PMID- 11246763
TI  - Pediatric. Length of stay guidelines.

PMID- 11246762
TI  - Saving lives and money. Stent use.

PMID- 11246765
TI  - Wasted opportunities. Report rips healthcare industry's failure to use IT to its
      full capabilities.

PMID- 11246764
TI  - 100 top hospitals. National benchmarks.

PMID- 11246766
TI  - The rule of law. Planned closure of Mass. hospital runs into state's patient
      protection law.

PMID- 11246767
TI  - Road to nowhere? Tennessee the latest battleground in debate over not-for
      profits' tax status.

PMID- 11246768
TI  - Back in the feud. CON battle between Novant, Carolinas HealthCare continues to
      escalate.

PMID- 11246769
TI  - The latest surgery suite, and a room with a view. Short-stay surgical hospitals
      boast hotellike amenities.

PMID- 11246770
TI  - At the heart of the matter. Cardiac-care hospital projects pit provider against
      provider.

PMID- 11246772
TI  - IPO resurgence. Healthcare services offerings show signs of life after two slow
      years.

PMID- 11246771
TI  - Chapter 11 snags one more. N.Y.'s Crouse Hospital will not close, merge or sell.

PMID- 11246773
TI  - Tort and retort. Florida lawmakers to consider changes in liability laws for
      nursing homes.

PMID- 11246775
TI  - XI European Meeting of the French Society of Cardiology. 17-20 January 2001.
      Paris, France. Abstracts.

PMID- 11246774
TI  - Hard bargaining. High court takes on highly charged issues of nursing duties vs.
      union eligibility.

PMID- 11246776
TI  - Could a tax cut generate unexpected help for the uninsured?

PMID- 11246777
TI  - New faces appear at key congressional committees.

PMID- 11246778
TI  - Regulatory review by the new administration: what's the impact?

PMID- 11246779
TI  - Congressional outlook: nursing shortages.

PMID- 11246780
TI  - Career patterns of healthcare executives.
AB  - This research examines the job and career changes of healthcare executives and
      managers working in different segments of the healthcare industry in the western
      United States. The results suggest that the job and career patterns in the
      healthcare delivery sector are undergoing significant transformation. One third
      of the respondents reports that at least one of their last four job changes was
      involuntary or unplanned. One half of those attempted to make a career change.
      This study identifies four different executive and management career patterns.
      The most common was one of multiple career changes. The second pattern was that
      of a single career change, followed by a 'traditional' career in which one did
      not seek a career change. The final pattern was characterized as a movement back
      and forth between two different segments of the healthcare industry. Age, gender,
      marital status and education were not associated with any specific career
      pattern. The need to achieve results early in the respondent's career had a
      strong influence on career patterns. This study confirms the fluidity of career
      movement and the changing permeability between the various segments of the
      healthcare industry. It also suggests that career success increasingly will
      require broad management experience in those different segments.

PMID- 11246781
TI  - Effect of organizational and environmental factors on service differentiation
      strategy of integrated healthcare networks.
AB  - During the past decade, the missions/goals of medical providers of healthcare
      services in the United States have shifted--from emphasizing individual,
      independent illness treatments to focusing on the continuum of care, population
      based wellness, and providing the appropriate care in the most efficient way.
      Integrated healthcare networks (IHNs)--or integrated healthcare delivery systems-
      have been focusing heavily on their level of various partnership integration
      (i.e. service differentiation strategy) in order to offer a full continuum of
      care. The aim of this study, using the individual IHN as the unit of analysis,
      was to identify organizational and environmental factors that influence IHN
      administrators to focus on their service differentiation of market lines,
      including the establishment of third-party payers' contracts, the affiliation of
      managed-care organizations, and the alliances of various nonhospital medical
      providers, to provide a continuum of care. The study findings show that tax
      status of an IHN, its age, and market competition affect its service
      differentiation strategy in the provision of a full continuum of care.

PMID- 11246782
TI  - Measurement of patient satisfaction in a public hospital in Ankara.
AB  - This article communicates the results of a patient satisfaction survey
      administered to 420 adults discharged from a major public hospital in Turkey. The
      direct measurement of patient satisfaction is a relatively new phenomenon for
      this country. A system was designed similar to those available in the US and was
      applied during an exit interview. Three areas of analysis were identified:
      accessibility and availability of services, perceived quality of patient care and
      organizational and administrative issues. Relationships and percentages within
      and among several variables are reported. Overall, most individuals were
      satisfied with direct patient care, although in some areas this varied
      significantly and was based on the education level of the respondent. In
      addition, many customers reported discontentment with organizational and
      administrative support services. We recommend that hospitals in Turkey adapt
      routine policies similar to those in the US for conducting these types of
      evaluations.

PMID- 11246783
TI  - Mediating the cultural boundaries between medicine, nursing and management--the
      central challenge in hospital reform.
AB  - This paper documents the resilience of medical and nursing profession-based
      subcultures and the extent of the differences between them. Against this
      background, we assess the capacity and willingness of medical and nursing
      managers to promote changes that will extend the accountability of clinicians and
      engender more evidence-based, financially driven and output-oriented approaches
      to service delivery.

PMID- 11246784
TI  - Cost of nosocomial infection in Turkey: an estimate based on the university
      hospital data.
AB  - Nosocomial infections significantly affect the resource needs of hospitalized
      patients. They increase the mortality and morbidity of affected individuals and
      expose hospital staff to increased risk of infection. To estimate the additional
      resources needed in the hospital sector to deal with such infections, a sample of
      infection cases was selected from the Hacettepe University Hospital in Ankara,
      Turkey. Each case of nosocomial infection was matched with a noninfected case
      after controlling for age, sex, clinical diagnosis etc. of the patients. The
      empirical results indicate that hospital infection increases the average hospital
      stay by about four days. Total cost of an infected case, on average, was found to
      be $442 higher than that for a matched noninfected case. Using this incremental
      cost estimate, projections for Turkey implies that the hospital sector had to
      spend an additional $48 million in 1995 for medical management of nosocomial
      infections. The benefit: cost ratio for a hospital-based infection control
      programme is found to be about 4.6. Clearly, a programme for preventing
      nosocomial infections will not only pay for itself but also will generate other
      direct and indirect benefits to patients and society as a whole.

PMID- 11246785
TI  - HIV/AIDS challenges the normative model of healthcare delivery in Canada.
AB  - With advances in therapeutics, effective therapy for human immunodeficiency virus
      (HIV) has shifted the focus of HIV care from an acute illness to a chronic
      disease requiring the services of several disciplines in a primary care setting.
      This article describes a collaborative model in the delivery of HIV care for HIV
      infected individuals who remain fragile, both physically and psychosocially.

PMID- 11246786
TI  - Economics and euthanasia.
AB  - This paper argues that a cost/benefit-type economic analysis of whether or not to
      prohibit euthanasia should not be undertaken by health services managers unless
      ethical issues have been resolved to a particular conclusion. A conclusion on
      ethical grounds in favour of the prohibition of euthanasia renders the
      consideration of economic criteria redundant. The case of the German euthanasia
      programme in the 1930s is used to illustrate the danger of attempting to combine
      ethical and economic criteria into a single decision rule.

PMID- 11246787
TI  - Cost analysis of dialysis modalities in Italy.
AB  - This study analyses management and costs of dialysis in the Italian National
      Health Service (NHS). Information on efficacy and health-related quality of life
      (HRQOL) based on the existing literature also is presented. The clinical
      differences between the dialysis modalities seem to be related to their
      appropriateness to specific patient groups. Efficacy rates are similar and the
      only differences are in complications and HRQOL. Traditional haemodialysis (THD)
      can be done by Italian patients in dialysis centres or in hospital. Highflux
      haemodialysis (HFHD) is generally only done in hospital. Peritoneal dialysis (PD)
      is usually done at home. The cost analysis was performed on a sample of Italian
      dialysis centres and hospitals, according to the full cost method. As expected,
      HFHD was more expensive than THD and PD, but no marked differences emerged among
      the different HFHD modalities. THD modalities in dialysis centres were less
      costly than in hospitals. Automated PD (APD) was much more expensive (almost
      twice) than continuous ambulatory PD (CAPD), the cheapest method in absolute
      terms. This study confirms that dialysis is costly and that it is very difficult
      to assess the cost-effectiveness of the different approaches. Although this study
      has limits, it should provide sufficient analytical information to local
      healthcare managers for more rational allocation of financial resources to
      dialysis services.

PMID- 11246788
TI  - American Roentgen Ray Society 101st Annual Meeting. April 29-May 4, 2001.
      Seattle, Washington, USA. Abstracts.

PMID- 11246789
TI  - Pumping iron Jr. Weight training won't stunt a child's growth, but the lifts have
      to be chosen with care. Here's how.

PMID- 11246791
TI  - New JCAHO standards require integrated patient safety program.
AB  - The Joint Commission on Accreditation of Healthcare Organizations is getting
      mostly positive reviews on its recently approved standards focused on patient
      safety and medical error reduction in hospitals. But experts warn that
      integrating these new standards into existing safety protocols will be no easy
      task. The new standards augment the nearly 50% of current Joint Commission
      standards related to patient safety. Requirements for establishing ongoing
      patient safety programs in organizations accredited under the Comprehensive
      Accreditation Manual for Hospitals will be added in the areas of leadership,
      management of information, and other functions.

PMID- 11246790
TI  - World wide waist.

PMID- 11246792
TI  - JCAHO gears up for patient confidentiality.
AB  - Hospitals gearing up to meet the patient privacy requirements of the Health
      Insurance Portability and Accountability Act should bear in mind that the Joint
      Commission has no plans to abandon its role in this area.

PMID- 11246793
TI  - Present comparative data effectively.
AB  - The Joint Commissions' ORYX project is impacting the way hospital caregivers
      evaluate performance. Ten years ago, there were very little data from external
      groups that could be used for comparative purposes. Today, with all the different
      report card initiatives, such data are easier to find. Now quality managers are
      facing the challenge of sharing these data with administrative and medical staff
      leaders in a way that allows for accurate evaluation.

PMID- 11246794
TI  - Satisfied patients yield better outcomes, revenue.

PMID- 11246795
TI  - Ohio rehab therapists learn the 24/7 standard.

PMID- 11246796
TI  - Winning physician support for your quality initiatives.
AB  - Joel Mattison, MD, a member of Hospital Peer Review's editorial board, offers
      practical tips for bringing physicians on board for hospital quality initiatives.
      He is the physician advisor in the department of clinical resource management and
      medical director at St. Joseph's Hospital in Tampa, FL.

PMID- 11246797
TI  - Quantification of Stachybotrys chartarum conidia in indoor dust using real time,
      fluorescent probe-based detection of PCR products.
AB  - Analyses of fungal spores or conidia in indoor dust samples can be useful for
      determining the contamination status of building interiors and in signaling
      instances where potentially harmful exposures of building occupants to these
      organisms may exist. A recently developed method for the quantification of
      Stachybotrys chartarum conidia, using real-time, fluorescence probe--based
      detection of PCR products (TaqMan system) was employed to analyze indoor dust
      samples for this toxigenic fungal species. Dust samples ofup to 10 mg were found
      to be amenable to DNA extraction and analysis. Quantitative estimates of S.
      chartarum conidia in composite dust samples, containing a four-log range of these
      cells, were within 25 -- 104% of the expected quantities in 95% of analyses
      performed by the method. Calibrator samples containing known numbers of S.
      chartarum conidia were used as standards for quantification. Conidia of an
      arbitrarily selected strain of Geotrichum candidum were added in equal numbers to
      both dust and calibrator samples before DNA extraction. Partial corrections for
      reductions in overall DNA yields from the dust samples compared to the calibrator
      samples were obtained by comparative analyses of rDNA sequence yields from these
      reference conidia in the two types of samples. Dust samples from two contaminated
      homes were determined to contain greater than 10(3) S. chartarum conidia per
      milligram in collection areas near the sites of contamination and greater than
      10(2) conidia per milligram in several areas removed from these sites in analyses
      performed by the method. These measurements were within the predicted range of
      agreement with results obtained by direct microscopic enumeration of presumptive
      Stachybotrys conidia in the same samples.

PMID- 11246798
TI  - Monitor-to-monitor temporal correlation of air pollution and weather variables in
      the North-Central U.S.
AB  - Numerous time series studies have reported associations between daily ambient
      concentrations of air pollution and morbidity or mortality. Recent personal
      exposure studies have also reported relatively high longitudinal correlation
      between personal exposures to particulate matter (PM) and home outdoor PM
      concentrations, lending support to the health effects reported in time series
      studies. However, the question remains as to how well the temporal fluctuations
      in the air pollution levels observed at an outdoor monitor represent the temporal
      fluctuations in the population exposures to pollution of outdoor origins in a
      city, and how such representativeness affects the size and significance of risk
      estimates. Also, such spatio-temporal correlations would vary from pollutant to
      pollutant, likely influencing their relative significance of statistical
      associations with health outcomes. In this study, we characterized the extent of
      monitor-to-monitor correlation over time among multiple monitoring sites for PM
      less than 10 microm (PM10), gaseous criteria pollutants, and several weather
      variables in seven central and eastern contiguous states (IL, IN, MI, OH, PA, WI,
      and WV) during the study period of 1988-1990. After removing seasonal trends, the
      monitor-to-monitor temporal correlation among the air pollution/weather variables
      within 100-mile separation distance in these areas could be generally ranked into
      three groups: (1 ) temperature, dew point, relative humidity (r>0.9); (2) O3,
      PM10, NO2 (r: 0.8-0.6); and (3) CO, SO2 (r<0.5). Using the subsets for separation
      distance less than 100 miles, regression analyses of these monitor-to-monitor
      correlation coefficients were also conducted with explanatory variables including
      separation distance, qualitative (land use, location setting, and monitoring
      objectives) and quantitative (large and small variance) site characteristics, and
      region indicators for Air Quality Control Region (AQCR). The separation distance
      was a significant predictor of monitorto-monitor correlation decline especially
      for PM10 and NO2 (approximately 0.2 drop over 30 miles). Site characteristic
      variables were, in some cases, significant predictors of monitor-to-monitor
      correlation, but the magnitude of their impacts was not substantial. Regional
      differences, as examined by AQCR, were in some cases (e.g., in Metropolitan
      Philadelphia) substantial. In these areas, the pollutants that had generally poor
      monitor-to-monitor correlation in the overall seven states data (i.e., for SO2
      and CO) showed higher monitor-to-monitor correlations, comparable with PM10 and
      O3, within the AQCR. These results are useful in interpreting some of the past
      time series epidemiological results. The differences in monitor-to-monitor
      correlations found across pollutants in this work (i.e., r approximately 0.8 vs.
      r approximately 0.4) are sufficiently large that they could be a factor in the
      different pollutant significance levels reported in the epidemiologic literature.
      It is recommended that future epidemiological studies collect and incorporate
      information on spatial variability among air pollutants in the analysis and
      interpretation of their results.

PMID- 11246799
TI  - Childhood respiratory symptoms, hospital admissions, and long-term exposure to
      airborne particulate matter.
AB  - The effects of long-term exposure to air pollution on respiratory symptoms and
      respiratory hospitalization (for asthma, bronchitis or pneumonia) were assessed
      in a cross-sectional study of children (ages 7--11 years, N=667) living in a
      moderately industrialized city in Central Slovakia. Individual health, residence
      and family history data obtained through the CESAR study were coupled, using
      Geographic Information System (GIS) technologies, with total suspended
      particulate (TSP) exposure estimates derived from dispersion modeling of almost
      all local stationary sources. These data were used to assess, at the intra-city
      level and child-specific level, the potential for TSP as a risk factor for
      respiratory disease in children. TSP, PM10, and PM2.5 monitored ambient
      concentrations are highly correlated in the study location. Modeled TSP
      concentrations resulting from local source emissions are dominated by a large
      wood processing facility, suggesting variation in exposures among children. The
      prevalence of respiratory non-asthmatic symptoms and hospitalizations was
      associated with increased TSP. No association between long-term exposure to TSP
      and asthma diagnosis or wheeze symptoms was found. Logistic regression modeling
      indicated a significant increase in hospital admissions for asthma, bronchitis or
      pneumonia associated with increasing air pollution (OR 2.16, CI, 1.01--4.60),
      doctor-diagnosed bronchitis (OR 1.53, CI, 1.02-2.30), and parent-reported chronic
      phlegm (OR 3.43, CI, 1.64--7.16), expressed as odds for a 15 microg/m3 increase
      in estimated TSP exposure, and these increases are not due to differences in
      socio-economic, health care or other identified factors.

PMID- 11246800
TI  - Household appliance use and residential exposure to 60-hz magnetic fields.
AB  - We characterized the distribution of exposure to magnetic fields (MFs) during
      daily activities and during household appliance use, and estimated the relative
      contribution of various activities and appliances to total daily exposure. One
      hundred sixty-two subjects provided information on their patterns of appliance
      use and wore personal monitors for 24 h to collect MF exposure data. Of total
      exposure, 27% accumulated while subjects were in bed; 41% while at home but not
      in bed; 9% at work; and 24% elsewhere. Less than 2% of the total MF exposure
      accumulated during the use of each of the eight individual appliances considered,
      except computers, during the use of which 9% of the total exposure accumulated.
      Of the time subjects spent at exposure levels higher than 2 microT, 8%
      accumulated while they were using microwave ovens, and 4% and 3% while using
      computers and electric stoves, respectively. Mean MF measurements tended to be
      lowest when subjects were in bed and highest at work and during the use of
      microwave ovens, coffee grinders, hair dryers, and electric shavers. Results from
      questionnaires on household appliance use in the past year were not useful in
      predicting the total mean exposure level and over-threshold exposures measured by
      24-h personal monitors. Significant MF exposure accumulates at home, at work, and
      elsewhere; therefore, accurate exposure assessment needs to consider residential,
      occupational, and other sources together. Questionnaire-based information on
      appliance use has limited value in the assessment of average and over-threshold
      exposure to MFs.

PMID- 11246802
TI  - Temporal changes in TCDD levels in 1419 Air Force Vietnam-era veterans not
      occupationally exposed to herbicides.
AB  - We summarize temporal changes in the distribution of 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) measurements made in serum drawn in 1987, 1992, and 1997 from 1419
      Air Force Vietnam-era veterans who served as comparisons in a 20-year prospective
      study of health and exposure to herbicides and their TCDD contaminant in Air
      Force veterans of Operation Ranch Hand, the unit responsible for aerial spraying
      of Agent Orange and other herbicides in Vietnam. Among comparison veterans, TCDD
      levels decreased significantly with time at a rate of -- 0.25 parts per trillion
      per year. We also describe paired serum TCDD measurements in a subgroup of 33
      veterans who had detectable levels in both 1987 and 1992. The paired measurements
      suggested that serum TCDD levels decreased with time, including those near the
      limit of detection.

PMID- 11246801
TI  - Design and validation of a high-flow personal sampler for PM2.5.
AB  - A high-flow personal sampler (HFPS) for airborne particulate matter has been
      developed and fully characterised, and validation tests have been carried out.
      The sampler is a low-cost gravimetric instrument designed to collect particulate
      matter with a 50% cut point at 2.5 microm aerodynamic equivalent diameter
      (PM2.5), where size selection is achieved by the use of porous polyurethane foam.
      Development of a porous foam selector was chosen over a cyclone or impactor due
      to the lightweight, low-cost, and compact design that could be achieved. The
      sampler flow rate of 16 1/min is achieved using a portable, flow-controlled pump;
      this flow rate is far higher than that of conventional personal samplers and the
      HFPS can therefore be used for personal sampling in the ambient environment over
      short sampling periods of much less than 24 h. The HFPS is currently being used
      in a study of particle exposure of urban transport users (cyclists, car drivers,
      bus and Underground rail passengers) where personal sampling over short time
      periods representing typical commuter journey times is required. The HFPS was
      fully characterised in chamber studies with a TSI aerodynamic particle sizer
      (APS). The sampler was then validated against a co-located U.S. EPA Federal
      Reference PM2.5 Well Impactor Ninety Six (WINS) and a KTL cyclone, and parallel
      testing was performed. Initial testing showed some penetration of particles
      through the porous foam structure; applying an oil coating to the foam eliminated
      this problem. Chamber testing was carried out on a number of different selector
      prototypes, with the final design giving a 50% penetration diameter (i.e., d50)
      of 2.4 microm at 16 1/min. The new sampler exhibited good agreement in three sets
      of co-located tests with established samplers, and parallel testing showed
      excellent agreement between paired HFPS samplers.

PMID- 11246803
TI  - On predicting multi-route and multimedia residential exposure to chlorpyrifos and
      diazinon.
AB  - This paper formulates regression models and examines their ability to associate
      exposures to chlorpyrifos and diazinon in residences with information obtained
      from questionnaires and environmental sampling of the National Human Exposure
      Assessment Survey Arizona (NHEXAS-AZ) database. A knowledge-based list of 29
      potential exposure determinants was assembled from information obtained from six
      questionnaires administered in the course of the study. This list was used to
      select the independent variables of each model statistically and electronically.
      Depending on the data type of dependent and independent variables, four classes
      of regression models were developed to determine desired associations. Route
      specific exposures were estimated using the indirect method of exposure
      estimation and measurements from the NHEXAS-AZ field study. The stepwise
      procedure was used to construct regression models. Significance level at P=0.10
      was used for entry and retention of independent variables in a model. Twelve
      significant regression models were formulated to quantify associations among
      exposures and other variables in the NHEXAS-AZ database. Route-specific exposures
      to pesticides associate significantly with questionnaire-based variables such as
      preparation of pesticides, use of pesticide inside the house, and income level;
      and with concentration variables in three media: dermal wipe, sill wipe, and
      indoor air. Models formulated in this study may be used to estimate exposures to
      each of the pesticides. Yet, the use of these models must incorporate clear
      statements of the assumptions made in the formulation as well as the coefficient
      of determination and the confidence and prediction intervals of the dependent
      variable.

PMID- 11246804
TI  - Placing facilitator in ED cuts avoidable hospital stays.

PMID- 11246805
TI  - DM programs take different roads to CHF success.
AB  - Improving CHF outcomes: There's no single right way. But there are some elements
      in common, as suggested by the experience of Duke, Kaiser Permanente, and First
      Priority Health. The challenge is to identify high-risk patients and provide as
      comprehensive an array of services as possible.

PMID- 11246806
TI  - Improve scheduling of fistula patients to slash unnecessary costs, improve care
      for ESRD.
AB  - A $20 cab ride makes the difference. When ESRD patients needed emergency surgery,
      Senatra Norfolk General Hospital found scheduling to be a huge problem. A little
      investigation and a $20 cab ride are two of the several tactics administrators
      used to cut costs dramatically among this population.

PMID- 11246807
TI  - Preventive health program aims to reduce cost, incidence of breast cancer.
AB  - Targeted prevention for breast cancer. BlueCross BlueShield of Minnesota and an
      affiliated pharmacy therapy company believes it can identify patients at risk of
      breast cancer so well that it's prevention program will enhance the members'
      quality of life while saving costs.

PMID- 11246808
TI  - Providers debate pros and cons of pneumonia vaccination at discharge.
AB  - When to vaccinate against pneumonia? Does it makes sense when patients are in the
      hospital? Or should patients wait for the first post-op visit with the PCP?
      Office-based and hospital-based physicians weigh the pros and cons of each.

PMID- 11246809
TI  - Millennium fat-cell lipolysis reveals unsuspected novel tracks.
AB  - Adipose tissue lipolysis, i.e., the catabolic process leading to the breakdown of
      triglycerides into fatty acids and glycerol, is often considered as a simple and
      well-understood metabolic pathway. However, progress on the hormonal regulation
      and molecular mechanism of fat-cell lipolysis is opening new avenues and points
      to a number of unanswered questions. Recent studies on the lipolytic beta- and
      antilipolytic alpha2-adrenergic control of lipolysis has allowed a better
      understanding of the relative contribution of the two types of receptors and
      provide strong evidence for the in vivo implication of alpha2-adrenoceptors in
      the physiological control of subcutaneous adipose-tissue lipolysis. A novel
      lipolytic system has been characterized in human fat cells. Natriuretic peptides
      stimulate lipolysis through a cGMP-dependent pathway. The molecular details of
      the lipolytic reaction are not fully understood. Translocation of hormone
      sensitive lipase, the rate-limiting enzyme of lipolysis, to the lipid droplet
      seems to be an important step during lipolytic activation. Reorganization of the
      lipid droplet coating by perilipins may also facilitate the access of the enzyme.
      Unexpectedly, hormone-sensitive lipase-deficient mice are not obese and show
      residual adipose-tissue lipolysis, which suggests the existence of another
      triglyceride lipase. Whether the expression of this uncharacterized neutral
      lipase is compensatory for the lack of hormone-sensitive lipase is an important
      question yet to be resolved. In humans, alterations of hormone-sensitive lipase
      expression are associated with changes in lipolysis in various physiological and
      pathological states. Genetic studies show that beta2-adrenoceptor and hormone
      sensitive lipase genes may participate in the polygenic background of obesity.

PMID- 11246810
TI  - The endocrine function of the fat cell-regulation by the sympathetic nervous
      system.
AB  - The landmark discovery of leptin established beyond question the fact that
      adipose tissue is a crucial active regulator of body weight, an endocrine organ
      in its own right and part of a feedback circuit possessing both afferent and
      efferent loops. This is in addition to its more established roles as a receiver
      of incoming endocrine signals and modulator of circulating hormones such as sex
      steroids. Since this discovery, much has been learned about the role of leptin in
      the afferent loop of the hypothalamic regulation of body weight and indeed about
      some of the neuro-endocrine circuitry involved in the regulation of appetite and
      weight. Much less, however, is known about the efferent limb of the circuit,
      specifically relating to how the hypothalamus is able to influence adipocyte
      behaviour and how this link may itself be influenced by endocrine and paracrine
      signals, both acting on and emanating from adipocytes themselves, acting at
      multiple levels. This review will focus on the role of the sympathetic nervous
      system (SNS) and adreno-medullary system in relation to the regulation of adipose
      tissue physiology and endocrine function. The evidence in support of the
      hypothesis that the SNS is a crucial mediator of the efferent loop of this
      feedback circuit will be considered.

PMID- 11246811
TI  - TSH receptor in adipose cells.
AB  - Although there have been reports supporting the presence of the TSH receptor
      (TSHR) in human adipose tissue, these findings are still not universally
      accepted. Contributing to the controversy is a paucity of data about the
      physiological role the TSH receptor might play in adipose cells. In addition to
      mature lipid-filled adipocytes, adipose tissue also harbors a pool of
      specialized, fibroblast-like preadipocytes within the stromal-vascular
      compartment. Upon appropriate induction, preadipocytes can either differentiate
      into adipocytes or undergo apoptosis. Since TSHR has been detected in
      preadipocytes and adipocytes, its potential impact on adipose tissue function may
      relate to differentiation stage-specific cellular properties.

PMID- 11246812
TI  - A marked upregulation of uncoupling protein 2 gene expression in adipose tissue
      of hyperthyroid subjects.
AB  - Recently, a family of uncoupling protein (UCP) genes has been discovered. The
      role of these genes is unknown, but it has been suggested that they are involved
      in regulating resting metabolic rate. In this study, we hypothesised that thyroid
      hormone status may influence the expression of UCP2 mRNA. The adipose tissue
      levels of UCP2 mRNA were measured in eight female subjects before and after
      treatment for thyrotoxicosis. All subjects in the hyperthyroid condition had
      markedly enhanced plasma levels of thyroxine (62.0 +/- 6.9 vs. 17.9 +/- 1.7, p =
      0.012) and triiodothyronine (37.9 +/- 6.9 vs. 5.9 +/- 0.9, p = 0.012),
      accelerated heart rate (94 +/- 7 vs. 69 +/- 5, p = 0.012), decreased BMI (24.5 +/
      1.9 vs. 25.1 +/- 1.9, p = 0.025) and decreased percentage body fat (32.8 +/- 4.4
      vs. 37.1 +/- 4.5, p = 0.018), as compared to the euthyroid state. Using RT
      competitive-PCR, the UCP2 mRNA levels were found to be 2.5-fold upregulated in
      hyperthyroidism (10.4 +/- 1.7 vs. 4.2 +/- 1.3 amol/microg RNA, p = 0.012). In
      contrast, no difference in expression levels of the reference gene 18SrRNA was
      seen in the hyperthyroid versus the euthyroid state (317 +/- 49 vs. 279 +/- 25
      amol/microg RNA, p = 0.48) but the difference in UCP2 mRNA levels between the
      hyper- and euthyroid state remained when UCP2 was related to 18SrRNA (p = 0.012).
      In conclusion, thyrotoxicosis markedly increases the expression of UCP2 mRNA in
      adipose tissue, which suggests a role for thyroid hormones in the regulation of
      this uncoupling protein in man.

PMID- 11246813
TI  - Nitric oxide production by adipocytes: a role in the pathogenesis of insulin
      resistance?

PMID- 11246814
TI  - Role of adipose tissue for cardiovascular-renal regulation in health and disease.
AB  - Obesity is associated with profound alterations of the cardiovascular system
      including an increase in systemic blood pressure. Several vasoactive factors,
      including non-esterified fatty acids, angiotensin II, prostaglandins, and nitric
      oxide are known to be produced by adipose tissue, and are therefore of particular
      interest regarding their potential role for the regulation of vascular tone and
      structure. In addition, central nervous system actions of the adipose tissue
      derived hormone leptin may contribute to increased sympathetic nervous system
      activity that is typically found in obesity. Enhanced leptin-driven renal
      sympathetic out-flow, in combination with low atrial natriuretic peptide plasma
      levels possibly due to over-expression of the natriuretic peptide clearance
      receptor in adipocytes, may enhance sodium retention and volume expansion, both
      key features in the pathophysiology of obesity-associated hypertension. In this
      review, we discuss these and other possible contributions of adipose tissue to
      the regulation of cardiovascular-renal function and speculate on the role of
      adipose tissue for the development of obesity-associated hypertension.

PMID- 11246815
TI  - Production of angiotensin II receptors type one (AT1) and type two (AT2) during
      the differentiation of 3T3-L1 preadipocytes.
AB  - During their development from progenitor cells, adipocytes not only express
      enzymatic activities necessary for the storage of triglycerides, but also achieve
      the capability to produce a number of endocrine factors such as leptin, tumor
      necrosis factor alpha (TNFalpha), complement factors, adiponectin/adipoQ,
      plasminogen activator inhibitor-1 (PAI-1), angiotensin II and others. Angiotensin
      II is produced from angiotensinogen by the proteolytic action of renin and
      angiotensin-converting enzyme; and several data point to the existence of a
      complete local renin-angiotensin system in adipose tissue, including angiotensin
      II receptors. In this study, we directly monitored the production of angiotensin
      II type one receptor (AT1) and angiotensin II type two receptor (AT2) proteins
      during the adipose conversion of murine 3T3-L1 preadipocytes by immunodetection
      with specific antibodies. AT1 receptors could be detected throughout the whole
      differentiation period. The strong AT2 signal in preadipocytes however was
      completely lost during the course of differentiation, which suggests that
      expression of AT2 receptors is inversely correlated to the adipose conversion
      program.

PMID- 11246817
TI  - Beta-Adrenoceptor agonists and other cAMP elevating agents suppress PAI-1
      production of human adipocytes in primary culture.
AB  - Recent studies showed that catecholamines contribute to the regulation of
      plasminogen activator inhibitor-1 (PAI-1) expression, at least in endothelial
      cells. Aim of this study was to examine the role of catecholamines on PAI-1
      production by human adipocytes and, in particular, to clarify which adrenoceptor
      (AR) subtypes are involved. Addition of the unselective AR agonist isoproterenol
      led to a dose- and time-dependent suppression of PAI-1 mRNA and protein release
      in adipocytes from the subcutaneous and omental depot of obese subjects. A
      similar degree of suppression was observed in subcutaneous mammary adipocytes of
      lean women. This effect was mainly mediated via the beta2-adrenoceptor according
      to experiments using selective agonists. Moreover, addition of cAMP-elevating
      agents such as dibutyryl-cAMP, forskolin and the phosphodiesterase inhibitors
      isobutyl-methylxanthine and milrinone resulted in a reduction of PAI-1 of varying
      degrees. In conclusion, the results of this study support the assumption that
      catecholamines are able to down-regulate PAI-1 expression and secretion in human
      adipocytes via beta-adrenergic receptors.

PMID- 11246816
TI  - Fat cell function and fibrinolysis.
AB  - Plasminogen activator inhibitor-1 (PAI-1) is a specific inhibitor of plasminogen
      activators and may be the principal regulator of plasminogen activation in vivo.
      PAI-1 levels are elevated in insulin-resistant subjects and are associated with
      an increased risk of atherothrombosis. After adjustment for metabolic parameters,
      increased PAI-1 levels were no longer considered as a cardiovascular risk factor.
      The mechanisms underlying the strong association between PAI-1 levels and the
      metabolic disturbances found in insulin resistance are still not understood.
      Several studies have suggested that visceral adipose tissue may be a major source
      of PAl-1. Accordingly, adipose tissue PAI-1 production particularly that from
      visceral fat, was found to be elevated in obese human subjects. Within human
      adipose tissue, stromal cells appear to be the main cells involved in PAI-1
      synthesis. This review discusses the potential mechanisms linking adipose tissue
      to plasma PAI-1 levels such as the intervention of cytokines (TNFalpha and
      TGFbeta), free fatty acids and hormones (insulin and glucocorticoids). Moreover
      alteration of adipose tissue cellular composition induced by the modulation of
      PAI-1 expression opens a novel field of interest.

PMID- 11246818
TI  - Regulation of plasminogen activitor inhibitor-1 in human adipose tissue:
      interaction between cytokines, cortisol and estrogen.
AB  - To investigate further the role of plasminogen activator inhibitor-1 (PAI-1) in
      human adipose tissue, the regulation of cytokines, cortisol (dexamethasone) as
      well as estrogen on PAI-1 were determined in human adipose tissue fragments. PAI
      1 activity was increased in human adipose tissue fragments incubated for 48 h
      with interleukin-1beta (IL-1beta) (2.6-fold, p < 0.01) and tumor necrosis factor
      alpha (2.3-fold, p < 0.01). Incubation with interleukin-6 revealed a non
      significant decrease in PAI-1 activity. Parallel findings were obtained when
      studying the PAI-1 mRNA expression. Dexamethesone increased PAI-1 activity after
      incubation for 8 h (p < 0.05) and enhanced the stimulation of IL-1beta after 8 h
      incubation. However, after 24 and 48 h, dexamethasone significantly reduced the
      IL-1beta induced increase in PAI-1 activity by 24-52% (p < 0.05), accordingly,
      PAI-1 mRNA expression was reduced 60%. Finally, the induction of PAI-1 activity
      and PAI-1 mRNA expression by IL-1beta was attenuated by estrogen (17.8+/-4.9%, p
      < 0.05 and 20.9+/-5.8%, p < 0.05, respectively). These results indicate that
      multiple cytokines, estrogen and dexamethasone may be involved in the regulation
      of PAI-1 biosynthesis in human adipose tissue, and suggest that there are
      interactions between cytokines and these steroid hormones. The interplay between
      these hormones may be of importance for the levels of PAI-1 observed in obesity
      and associated states.

PMID- 11246819
TI  - The abdominal obesity phenotype and insulin resistance are associated with
      abnormalities of the hypothalamic-pituitary-adrenal axis in humans.

PMID- 11246820
TI  - Sex steroid hormones, sex hormone-binding globulin, and obesity in men and women.
AB  - Sex steroid hormones in both males and females have been closely related to the
      regulation of adiposity, either through direct or indirect physiological
      mechanisms. Evidence also suggests a direct relationship between sex hormones and
      risk factors for cardiovascular disease. In the present review article, we will
      discuss recent studies that have examined the complex interrelationships between
      sex hormones, SHBG, obesity and risk factors for cardiovascular disease. Male
      obesity and excess abdominal adipose tissue accumulation is associated with
      reductions in gonadal androgen and low adrenal C19 steroid concentrations.
      Reduced C19 steroids are also related to an altered metabolic risk factor profile
      including glucose intolerance and an atherogenic dyslipidemic state. However, the
      concomitant visceral obese state appears as a major correlate in these
      associations. In women, menopause-induced estrogen deficiency and increased
      androgenicity are associated with increased abdominal obesity and with the
      concomitant alterations in the metabolic risk profile. The accelerated accretion
      of adipose tissue in the intra-abdominal region coincident with the onset of
      menopause may explain part of the increased risk of cardiovascular disease in
      postmenopausal women. In both men and women, plasma levels of sex hormone-binding
      globulin are strong correlates of obesity and risk factors for cardiovascular
      disease, and more importantly, the relationships between low SHBG and altered
      plasma lipid levels appear to be independent from the concomitant increased
      levels of visceral adipose tissue. SHBG concentration may, therefore, represent
      the most important and reliable marker of the sex hormone profile in the
      examination of the complex interrelation of sex steroid hormones, obesity, and
      cardiovascular disease risk.

PMID- 11246821
TI  - Interleukin-8 production in human adipose tissue. inhibitory effects of anti
      diabetic compounds, the thiazolidinedione ciglitazone and the biguanide
      metformin.
AB  - Obesity and Type 2 diabetes are associated with an increased risk of developing
      cardiovascular disease. Reports have suggested that the chemokine, interleukin-8,
      may be involved in the development of diabetic macroangiopathy as well as in the
      pathogenesis of atherosclerosis. Two classes of drugs, the biguanides and the
      insulin-sensitizing thiazolidinediones seem to have additional beneficial effects
      on cardiovascular risk-factors besides their effects on glucose homeostasis. In
      this study, we investigated the effects of the thiazolidinedione, Ciglitazone,
      the peroxisome proliferator-activated receptor alpha-agonist 5,8,11,14
      eicosatetraynoic acid (ETYA) and the biguanide, Metformin on interleukin-8 gene
      expression and production in human adipose tissue in vitro. Ciglitazone 10-100 M
      inhibited interleukin-8 release by 25-33% (p < 0.05) and mRNA expression by 33
      60% (p < 0.05). Metformin 0.1-10 mM inhibited interleukin-8 release by 20-50% (p
      < 0.05) and mRNA expression by 20-90% (p < 0.05). However, ETYA did not effect
      the production of interleukin-8 in the adipose tissue. In conclusion, we
      demonstrate the ability of two anti-diabetic compounds to decrease the release of
      interleukin-8 from human adipose tissue in vitro. These findings open the
      possibility that the beneficial effects on cardiovascular risk-factors of these
      anti-diabetic compounds might involve a reduction in the interleukin-8 produced
      in human adipose tissue.

PMID- 11246822
TI  - Regulation of metallothionein gene expression and secretion in rat adipocytes
      differentiated from preadipocytes in primary culture.
AB  - The gene encoding metallothionein, a low mol. wt. metal binding and stress
      response protein, is expressed in white adipose tissue. In the present study,
      metallothionein (MT-1) gene expression and factors regulating metallothionein
      production have been examined in adipocytes induced to differentiate from
      fibroblastic preadipocytes in primary cell culture. On the induction of
      differentiation, the metallothionein-1 gene was strongly expressed in the cells
      and metallothionein released into the medium. A peak in metallothionein-1 mRNA
      level and metallothionein secretion occurred at 2 and 10 days post
      differentiation, respectively, with a decrease in protein release after this
      time. The metallothionein-1 gene was expressed in the adipocytes prior to the
      adipsin and lipoprotein lipase genes, suggesting that it is an early marker of
      adipocyte differentiation. The addition of the glucocorticoid, dexamethasone, led
      to a substantial increase in metallothionein-1 mRNA in the cells and
      metallothionein secretion. Insulin and leptin also stimulated metallothionein
      production, although the effect was small. Neither noradrenaline nor the beta3
      adrenoceptor agonist, BRL 37 344, altered metallothionein release but forskolin
      and bromo-cAMP were stimulatory, markedly increasing both metallothionein-1 level
      and metallothionein secretion. It is suggested that metallothionein is a novel
      secretory product of the differentiated white adipocyte and that its production
      is regulated particularly by glucocorticoids and through a cAMP-dependent
      pathway.

PMID- 11246824
TI  - IGF-I- and IGFBP-3-expression in cultured human preadipocytes and adipocytes.
AB  - The expression and secretion of IGF-I and IGFBP-3 were investigated in cultured
      human preadipocytes and in in vitro differentiated adipocytes derived from human
      subcutaneous adipose tissue under chemically defined culture conditions. Human
      preadipocytes expressed mRNAs for IGF-I and IGFBP-3 and secreted the
      corresponding proteins into the culture medium as measured by sensitive
      radioimmunoassays. In human adipocytes; specific mRNA-expression was comparable
      to that found in preadipocytes, but IGF-I secretion was increased 10-fold (3.87
      +/- 0.69 vs. 0.41 +/- 0.11 ng/ml/10(6) cells/48 hrs, p < 0.05) and IGFBP-3
      secretion 2.5-fold (7.34+/-1.15 vs. 3.27+/-0.38 ng/ml/10(6) cells/48 hrs, p<0.05)
      in the presence of adipogenic medium probably resulting in an increase of unbound
      IGF-I. Under serum-free, chemically defined conditions human growth hormone (hGH)
      and insulin were found to be positive regulators and cortisol was found to be a
      negative regulator of IGF-I and IGFBP-3 secretion in preadipocytes. In cultured
      human adipocytes, hGH showed no effect on IGF-I and IGFBP-3 secretion, whereas
      insulin stimulated and cortisol inhibited the secretion of both proteins. We
      conclude that IGF-I and IGFBP-3 may not only exert their actions in human adipose
      tissue via circulation, but also in an auto/paracrine way.

PMID- 11246826
TI  - Smoking cessation. Pulling out the stops.
AB  - The launch of smoking-cessation drug Zyban in June last year greatly increased
      demand on a local smoking-cessation service. It is important to use local media
      to increase awareness of local services. Health authorities and pharmaceutical
      companies should work with the media when new drugs may put extra strain on local
      services.

PMID- 11246823
TI  - Influences of ionomycin, dibutyryl-cycloAMP and tumour necrosis factor-alpha on
      intracellular amount and secretion of apM1 in differentiating primary human
      preadipocytes.
AB  - 3T3-L1-adipocytes produce the adipocyte complement related protein of 30 kD
      (Acrp30), which is also designated as AdipoQ. In order to study the expression
      and secretion of the human homologue of this protein, apM1 (adipose Most abundant
      gene transcript 1, also named gelatin-binding protein of 28 kD [GBP28] or
      adiponectin), a polyclonal antibody was produced. Both expression and secretion
      can be detected beginning with day 4 after induction of differentiation. The
      amount of expressed apM1 correlates with the specific activity of the
      differentiation marker glycerol-3-phosphate dehydrogenase. Secretion of apM1 is
      increased by the addition of ionomycin. Both the nonhydrolysable dibutyryl
      cycloAMP and tumour necrosis factor alpha reduce the expression and secretion of
      apM1.

PMID- 11246825
TI  - Mental health. Doing the hurdles.
AB  - A survey of senior mental health managers in London found that less than half
      thought they would stay in their job more than a year. The resulting turnover
      could create significant instability. Respondents considered the development of
      community mental health teams as the top priority for implementation. Financial
      restrictions were seen as the major obstacle to service development. Most
      respondents welcomed the national service framework for mental health.

PMID- 11246827
TI  - Primary care groups. Voice recognition.
AB  - A survey of primary care groups in the South West region found a lack of
      expertise in involving the public. Respondents saw the main obstacles as lack of
      time, expertise and money. If the NHS plan's ambitious agenda for public
      involvement is to be achieved the shortage of expertise must be addressed.

PMID- 11246828
TI  - Welfare. Mutual benefits.

PMID- 11246829
TI  - Two's a crowd.

PMID- 11246830
TI  - AHA's Rick Pollack reflects on BBA battle, discusses new political landscape.

PMID- 11246831
TI  - Free transportation to hospital patients approved in OIG advisory opinion.

PMID- 11246832
TI  - In the face of adversity, hospitals win again in budget battle.

PMID- 11246833
TI  - The epidemiologic transition. A theory of the Epidemiology of population change.
      1971.

PMID- 11246834
TI  - Web sites for health care law practitioners.

PMID- 11246835
TI  - Fiduciary duty litigation experiences setbacks. Peterson v. Connecticut General
      Life Insurance Co. and Neade v. Portes.

PMID- 11246836
TI  - Joint Commission's medical staff standards for 2001.

PMID- 11246837
TI  - Hypertension control improved through patient education. Chinese PEP
      Investigators.
AB  - OBJECTIVE: To evaluate the effects of patient education for hypertension on
      hypertension control. METHODS: Of 169 eligible patients (systolic blood pressure
      > or = 160 mmHg and/or diastolic blood pressure > or = 95 mmHg), 60 were assigned
      to educational group (group E, antihypertensive drug treatment with an addition
      of patient education) and 109 to routine group (group R, antihypertensive drug
      treatment alone). The average follow-up approximated to 3 years. RESULTS: The
      blood pressure was reduced from at baseline and sustained in the three-year
      follow-up by 20/13 mmHg in group E and by 22/13 mmHg in group R. For this similar
      blood pressure reduction, about 10 mg less of metoprolol and 6 mg less of
      nitrendipine were used in group E than in group R. The percentage of the patients
      in whom goal blood pressure (under 160/90 mmHg) was achieved during follow-up was
      higher and progressively increased in group E (1st year: 65%, 2nd year: 72%) in
      comparison with in group R (1st year: 45%; 2nd year: 55%). Body weight was
      significantly reduced by 1.36 and 1.81 kg from at baseline to at the 1st and 2nd
      year repeated measurements in group E. The significant reduction from at baseline
      to at the 2nd year was significantly different from that in group R (P = 0.02).
      For 24-hour urinary sodium excretion, it was decreased in the group E, whereas it
      was increased in the group R. The cumulative rates of hypertension-related
      complications were 4.43% in group E and 7.02% in group R (absolute difference =
      2.59%, P = 0.48). The rate of missed appointments was somewhat higher in group R
      (10%) than in group E (7%) during the first year but lower in the 2nd and 3rd
      year (R vs E: 10% vs 2% in the 2nd year; 8% vs 2% in the 3rd year). Four patients
      lost to follow-up in group R (6.87%) and 1 patient in group E (1.74%, P = 0.08).
      CONCLUSION: The findings of this study suggest that patient education is of some
      benefits to the hypertension control.

PMID- 11246838
TI  - Effects of mammographic density and benign breast disease on breast cancer risk
      (United States).
AB  - BACKGROUND: Having either a history of benign breast disease, particularly
      atypical hyperplasia or extensive mammographic breast density, is associated with
      increased breast cancer risk. Previous studies have described an association
      between benign breast disease histology and breast density. However, whether
      these features measure the same risk, or are independent risk factors, has not
      been addressed. METHODS: This case-control study, nested within the prospective
      follow-up of the Breast Cancer Detection Demonstration Project, evaluated both
      benign histologic and mammographic density information from 347 women who later
      developed breast cancer and 410 age- and race-matched controls without breast
      cancer. Multivariate logistic regression analyses provided maximum-likelihood
      estimates of the odds ratios (OR) and 95% confidence intervals (CI) to evaluate
      the relative risk of breast cancer associated with each exposure. RESULTS:
      Adjusting for mammographic density, the OR for atypical hyperplasia was 2.1 (95%
      CI: 1.3-3.6), and adjusting for benign breast histology, the OR for > or = 75%
      density was 3.8 (95% CI: 2.0-7.2). Women with nonproliferative benign breast
      disease and > or = 75% density had an OR of 5.8 (95% CI: 1.8-18.6), and women
      with < 50% density and atypical hyperplasia had an OR of 4.1 (95% CI: 2.1-8.0).
      CONCLUSIONS: In this study, both benign breast disease histology and the
      percentage of the breast area with mammographic density were associated with
      breast cancer risk. However, women with both proliferative benign breast disease
      and > or = 75% density were not at as high a risk of breast cancer due to the
      combination of effects (p = 0.002) as women with only one of these factors.

PMID- 11246839
TI  - Incidence of cancer among women using long versus monthly cycle hormonal
      replacement therapy, Finland 1994-1997.
AB  - OBJECTIVE: This study was initiated as a consequence of a clinical observation in
      one hospital of several endometrial carcinomas among users of a fixed combination
      of a 3-month cycle oral hormonal replacement therapy (HRT), which has been
      marketed in Finland since 1990. We studied whether the use of 3-month ("long")
      cycle HRT is accompanied by a higher risk of endometrial cancer than the use of
      monthly cycle HRT. METHODS: A nationwide cohort of 15,956 long cycle and 78,549
      monthly cycle HRT users since January 1994 was extracted from the files of the
      national medical reimbursement register and followed up for cancer incidence
      through the Finnish Cancer Registry up to the end of 1997. RESULTS: There were 61
      cases of endometrial cancer among long cycle HRT users which significantly
      exceeds the average incidence in the Finnish population (standardized incidence
      ratio (SIRlong) 2.0, 95% confidence interval (CI) 1.6-2.6). The SIR among users
      of monthly cycle HRT products (SIRmonthly) was 1.3 (1.1-1.6) and the ratio
      SIRlong/SIRmonthly thus 1.5 (95% CI 1.1-2.1). Endometrial cancers among long
      cycle HRT users occur more often in early stages than in the general population
      and are more often highly differentiated. A survey of a sample of endometrial
      cancer patients in the long cycle HRT group revealed that all of them also had a
      history of other HRT. Users of both long and monthly cycle HRT had a similar
      statistically significant 30% excess of breast cancer in comparison to national
      incidence rates, while the incidence of colon cancer was decreased in both
      groups. There was no difference between the HRT groups in overall cancer
      morbidity. CONCLUSIONS: Our results imply that all HRT users have an increased
      risk of endometrial cancer, and long cycle HRT carries a higher relative risk
      than monthly cycle HRT. However, in this non-randomized setting it is impossible
      to judge whether this excess is attributable to the type of HRT or to patient
      selection. In-depth studies are needed to find out possible dose-response
      associations and to evaluate the role of potential confounders in detail.

PMID- 11246840
TI  - Diet and nutrition as risk factors for multiple myeloma among blacks and whites
      in the United States.
AB  - OBJECTIVES: To explore whether dietary factors contribute to the risk of multiple
      myeloma and the two-fold higher incidence among blacks compared to whites in the
      United States. METHODS: Data from a food-frequency questionnaire were analyzed
      for 346 white and 193 black subjects with multiple myeloma, and 1086 white and
      903 black controls who participated in a population-based case-control study of
      multiple myeloma in three areas of the United States. RESULTS: Elevated risks
      were associated with obese vs. normal weight (OR = 1.9, 95% confidence interval
      (CI) = 1.2-3.1 for whites and OR = 1.5, 95% CI = 0.9-2.4 for blacks), while the
      frequency of obesity was greater for black than white controls. Reduced risks
      were related to frequent intake of cruciferous vegetables (OR = 0.7, 95% CI = 0.6
      0.99) and fish (OR = 0.7, 95% CI = 0.5-0.9) in both races combined, and to
      vitamin C supplements in whites (OR = 0.6, 95% CI = 0.5-0.9) and blacks (OR =
      0.8, 95% CI = 0.5-1.4), with the frequency of vitamin supplement use being
      greater for white than black controls. However, frequent intake of vitamin C from
      food and supplements combined was associated with a protective effect in whites
      (OR = 0.6, 95% CI = 0.4-0.9), but not blacks (OR = 1.2, 95% CI = 0.8-2.1).
      CONCLUSIONS: The greater use of vitamin C supplements by whites and the higher
      frequency of obesity among blacks may explain part of the higher incidence of
      multiple myeloma among blacks compared to whites in the United States. In
      addition, the increasing prevalence of obesity may have contributed to the upward
      trend in the incidence of multiple myeloma during recent decades.

PMID- 11246841
TI  - Tubal sterilization and risk of breast cancer mortality in US women.
AB  - OBJECTIVE: To investigate the hypothesis that tubal sterilization is associated
      with a reduced risk of breast cancer. METHODS: We examined this hypothesis in a
      large prospective study of US adults. After 14 years of mortality follow-up, 3837
      deaths from breast cancer were observed in a cohort of 619,199 women who were
      cancer-free at study entry in 1982. RESULTS: Cox proportional hazards models
      (adjusted for multiple breast cancer risk factors) showed a significant inverse
      association between tubal sterilization and breast cancer mortality (adjusted
      rate ratio (RR) = 0.82, 95% confidence interval (CI) 0.70-0.96). Women who were
      sterilized before age 35 had a lower risk (adjusted RR = 0.69, 95% CI 0.53-0.88)
      than women who were sterilized at 35 years of age or older (adjusted RR = 0.92,
      95% CI 0.75-1.13). Also, sterilizations performed before 1975 resulted in a lower
      risk (RR = 0.75, 95% CI 0.62-0.91) than those performed during or after 1975 (RR
      = 0.98, 95% CI 0.74-1.29), possibly reflecting the likelihood of greater tissue
      damage with earlier procedures. CONCLUSIONS: These results suggest that tubal
      sterilization may lower subsequent risk of breast cancer, especially among women
      who are sterilized at a relatively young age. Additional studies are needed to
      confirm or refute these findings.

PMID- 11246842
TI  - Physical activity and breast cancer risk: the Women's Health Study (United
      States).
AB  - OBJECTIVE: It is biologically plausible for physical activity to decrease breast
      cancer risk; however, epidemiologic studies have yielded inconsistent findings.
      We therefore examined physical activity and breast cancer risk in the Women's
      Health Study. METHODS: We assessed physical activity among 39,322 apparently
      healthy women, aged > or = 45 years, and prospectively followed them for an
      average of 48 months. Four hundred eleven women developed breast cancer, with 222
      positive for both estrogen and progesterone receptors. RESULTS: Among all women
      the multivariate relative risks of all breast cancer associated with < 840, 840
      2519, 2520-6299, and > or = 6300 kJ/week expended on recreational activities and
      stair climbing were 1.00 (referent), 1.04 (95% confidence interval, 0.77-1.40),
      0.86 (0.64-1.17), and 0.80 (0.58-1.12), respectively; p-trend = 0.11. However,
      among postmenopausal women there was a significant inverse trend for all breast
      cancer; the corresponding relative risks were 1.0 (referent), 0.97 (0.68-1.4),
      0.78 (0.54-1.1), and 0.67 (0.44-1.0), respectively; p-trend = 0.03. Physical
      activity was unrelated to breast cancers positive for both estrogen and
      progesterone receptors either among all or postmenopausal women (p-trend = 0.50
      and 0.26, respectively). When we assessed only vigorous recreational activity,
      requiring > or = 6 METs or multiples of resting metabolic rate, we observed no
      significant associations with all or steroid hormone receptor positive breast
      cancer, either among all or postmenospausal women. CONCLUSIONS: These data
      suggest that physical activity during middle age and older is not uniformly
      associated with decreased breast cancer risk. Among postmenopausal women only,
      higher levels of physical activity may decrease the risk of breast cancer. This
      study, however, had limited statistical power to detect small effects.

PMID- 11246843
TI  - Completeness in an African cancer registry.
AB  - OBJECTIVE: A high level of completeness of case-finding is essential if data from
      cancer registries are to be useful for comparative studies. A large case series,
      collected independently of the cancer registry case-finding mechanisms, as part
      of a study of the influence of HIV infection on cancer risk, was used to evaluate
      the completeness of the registry in Kampala, Uganda, for the years 1994-1996.
      RESULTS: For adults aged 15 or more, the completeness of registration of
      diagnosed cancer cases was 89.6% (95% CI 87.0-91.7) overall. It varied with age
      (better ascertainment of younger cases, aged under 30) and cancer site (with
      Kaposi sarcoma cases significantly better identified), and cases with a histology
      report were more likely to be registered than those without (though the
      difference was not significant). Completeness declined with time, as in most
      registries, which continue to identify "late" cases some time after the initial
      diagnosis. CONCLUSION: This is the first objective measurement of completeness of
      cancer registration in Africa, and it gives reassurance that published incidence
      rates are reasonablyaccurate (provided that there is not an insistence on the
      very latest results).

PMID- 11246844
TI  - Associations between smoking and adenocarcinomas and squamous cell carcinomas of
      the uterine cervix (United States).
AB  - OBJECTIVES: Few studies of smoking and cervical carcinoma have addressed the rare
      cervical adenocarcinomas or used DNA-based tests to control for human
      papillomavirus (HPV) infection. METHODS: This multicenter case-control study
      included 124 adenocarcinoma cases, 307 community controls (matched on age, race,
      and residence to adenocarcinoma cases), and 139 squamous carcinoma cases (matched
      on age, diagnosis date, clinic, and disease stage to adenocarcinoma cases).
      Participants completed risk-factor interviews and volunteered cervical samples
      for PCR-based HPV testing. Polychotomous logistic regression generated adjusted
      odds ratios (ORs) and 95% confidence intervals (CIs) for both histologic types.
      RESULTS: Eighteen percent of adenocarcinoma cases, 43% of squamous carcinoma
      cases, and 22% of controls were current smokers. After control for HPV and other
      questionnaire data, adenocarcinomas were consistently inversely associated with
      smoking (e.g. current: OR = 0.6, 95% CI 0.3-1.1; > or = 1 pack per day: OR = 0.7,
      95% CI 0.4-1.3), while squamous carcinomas were positively associated with
      smoking (e.g. current: OR = 1.6, 95% CI 0.9-2.9; > or = 1 pack per day: OR = 1.8,
      95% CI 1.0-3.3). Results in analyses restricted to HPV-positive controls were
      similar. CONCLUSION: Smoking has opposite associations with cervical
      adenocarcinomas and squamous carcinomas. Although both histologic types are
      caused by HPV and arise in the cervix, etiologic co-factors for these tumors may
      differ.

PMID- 11246845
TI  - Dietary patterns, nutrient intake and gastric cancer in a high-risk area of
      Italy.
AB  - OBJECTIVES: To better understand the role of overall dietary patterns and major
      energy-providing components in gastric cancer etiology. METHODS: In a population
      based case-control study conducted in a high-risk area in central Italy, 382
      gastric cancer cases and 561 controls were available for analysis. Multivariate
      models based on energy-adjusted residuals and completely partitioned logistic
      models were used; dietary patterns were evaluated by factor analysis and multiple
      correspondence analysis. RESULTS: Gastric cancer risk was inversely related to
      high energy-adjusted intakes of vegetable fat, sugar, beta-carotene, vitamin C,
      alpha-tocopherol, and nitrates. In contrast, significant positive associations
      emerged with high intake of protein, nitrite, and sodium. According to energy
      decomposition models, gastric cancer risk increased with increasing intake of
      protein and decreased with increasing intake of sugar and total fat. The pattern
      analysis identified four dietary profiles, overall explaining 75% of total
      dietary variability. Two patterns, named "traditional" and "vitamin-rich", were
      strongly associated with gastric cancer risk and overall accounted for 44% of
      estimated gastric cancer attributable risk. The other two patterns, "refined" and
      "fat-rich", were not consistently associated with gastric cancer. CONCLUSION:
      Innovative methodological approaches may contribute to better evaluation of the
      complex relationship between diet and cancer risk and to planning dietary
      interventions.

PMID- 11246846
TI  - Anorexia nervosa and cancer risk.
AB  - OBJECTIVE: Energy restriction reduces the incidence of malignant tumors in
      experimental animals, but evidence for a similar effect in humans is lacking. To
      test the hypothesis in humans, we investigated cancer incidence among patients
      with anorexia nervosa, who have had an extremely low intake of calories for
      prolonged periods of their lives. METHODS: Patients with anorexia nervosa (2151
      women and 186 men) during 1970-1993 were identified in the population-based
      Danish Psychiatric Case Register and the National Registry of Patients. The
      cohort was linked to the Danish Cancer Registry, and cancer incidence among
      cohort members was compared with that of the general population. RESULTS: The
      overall cancer incidence among women with anorexia nervosa was reduced by a
      factor of 0.80 (95% confidence interval 0.52-1.18) below that of the general
      population on the basis of 25 observed and 31.4 expected cases. Among men, two
      cases of cancer were observed, both confined to the brain, whereas 0.2 cases were
      expected. CONCLUSIONS: The finding of a slight reduction in cancer risk among
      women with anorexia nervosa may support the theory that a low-energy diet may
      decrease tumor development in humans. However, longer follow-up and control for
      confounding factors are needed to obtain more convincing evidence.

PMID- 11246847
TI  - Smoking during pregnancy and breast cancer risk in very young women (United
      States).
AB  - OBJECTIVE: To evaluate the association of smoking during a woman's first
      pregnancy, a period of pronounced growth and differentiation of mammary tissue,
      and her subsequent breast cancer risk. METHODS: In this matched case-control
      study, we used linked birth certificate and tumor registry data from the New York
      State Health Department. Cases were 319 women aged 26-45 who were diagnosed with
      breast cancer in New York State between 1989 and 1995 and who completed a first
      pregnancy in New York State after 1987 at least one year prior to diagnosis of
      cancer. Controls were 768 primiparous women matched to cases on county of
      residence and delivery date. Information on prenatal smoking and other factors
      characterizing the woman's first pregnancy was obtained from the pregnancy record
      of each subject, and the association of these factors to breast cancer risk was
      assessed using conditional logistic regression. RESULTS: Smoking during pregnancy
      was associated with increased risk for breast cancer (crude OR = 2.7, 95%
      confidence interval (CI): 1.1-6.3). Adjustment for maternal age, subject age,
      race, and education strengthened this association (OR = 4.8, CI 1.6-14.6).
      CONCLUSIONS: These findings suggest that cigarette smoking during a woman's first
      pregnancy may increase her risk for early-onset breast cancer.

PMID- 11246848
TI  - A prospective cohort study of physical activity and body size in relation to
      prostate cancer risk (United States).
AB  - OBJECTIVES: To examine the associations of physical activity and body size with
      risk of prostate cancer. METHODS: At baseline in 1988, 8922 men (mean age 67
      years) completed a health questionnaire which included information on physical
      activity, body weight, and waist girth. In a subgroup (74% of men), physical
      activity data also had been provided in 1962 or 1966 and again in 1977.
      Additionally, body weight measured at age 18 was available for 92% of men. During
      follow-up from 1988 through 1993, 439 men developed prostate cancer. RESULTS: In
      multivariate analyses that accounted for potential confounders, the RRs (95% CI)
      for < 4200, 4200-8399, 8400-12,599, and > or = 12,600 kJ/week of physical
      activity at baseline were 1.00 (referent), 1.13 (0.84-1.52), 0.96 (0.68-1.35),
      and 1.04 (0.79-1.38), respectively. For body mass indexes (BMI) of < 22.5, 22.5
      24.9, 25.0-27.4, and > or = 27.5 kg/m2 at baseline, corresponding results were
      1.00 (referent), 1.27 (0.94-1.71), 1.26 (0.92-1.72), and 1.02 (0.68-1.53),
      respectively. For waist girths of < or = 86.4, 86.5-91.4, 91.5-96.5, and > 96.5
      cm, they were 1.00 (referent), 1.30 (0.96-1.76), 1.31 (0.96-1.80), and 1.19 (0.85
      1.65), respectively. Combining physical activity measures from the past, or
      examining vigorous activities only, did not yield any significant associations.
      BMI at age 18 also was not related to risk. CONCLUSION: These findings do not
      support a role of physical activity or body weight in prostate cancer etiology.

PMID- 11246849
TI  - Risk of breast cancer in female flight attendants: a population-based study
      (Iceland).
AB  - OBJECTIVES: To study whether increased cancer risk, particularly of cancer types
      previously related to radiation, was found among cabin attendants, using
      employment time as a surrogate of exposure to cosmic radiation. METHODS: A cohort
      of 1690 cabin attendants, 158 men and 1532 women from the Icelandic Cabin Crew
      Association and two airline companies in Iceland, was established. Cancer sites
      were ascertained between 1955 and 1997 by follow-up in a cancer registry. The
      personal identification number of each subject was used in record linkage to
      population-based registers containing vital and emigration status, reproductive
      factors and histologically verified cancer diagnosis. Standardized incidence
      rates (SIR) of different cancer sites in relation to employment time and year of
      hiring were calculated, as well as predictive values of breast cancer risk for
      evaluating possible confounding due to reproductive factors. RESULTS: The total
      number of person-years was 27,148. Among the women, 64 cancers were observed
      whereas 51.63 were expected (SIR 1.2, 95% CI 1.0-1.6), and significantly
      increased risk for malignant melanoma (SIR 3.0, 95% CI 1.2-6.2) was found.
      Significantly increased risks of overall cancers (SIR 1.3, 95% CI 1.0-1.8) and
      breast cancer (SIR 1.6, 95% CI 1.0-2.4) were observed among the female cabin
      attendants when 15 years lag time was applied. Those hired in 1971 or later had
      the heaviest exposure to cosmic radiation at a young age and had significantly
      increased risk of overall cancer (SIR 2.8, 95% CI 1.4-4.9) and breast cancer (SIR
      4.1, 95% CI 1.7-8.5). Predictive values calculated on the basis of reproductive
      factors among the cabin attendants and the population, and risk of breast cancer
      were 1.0 for parous vs. nulliparous, 1.0 for number of children, and 1.1 for age
      at birth of first child. CONCLUSION: The increased risk of breast cancer and
      malignant melanoma among cabin attendants seems to be occupationally related. The
      part played by occupational exposures, i.e. cosmic radiation, disturbance of the
      circadian rhythm, and electromagnetic fields or combination of these factors in
      the etiology of breast cancer among the cabin crew, is still a puzzle as
      confounding due to parity appears to be ruled out. The relationship between the
      sunbathing habits of the cabin crew and the increased risk of malignant melanoma
      needs to be clarified. There is also an urgent need to elucidate the importance
      of these findings for today's aviation.

PMID- 11246850
TI  - [Bone marrow transplant].

PMID- 11246851
TI  - Sugar conformation of a stereospecific 2'-R or 2'-S deuterium-labeled DNA decamer
      studied with proton-proton J coupling constants.
AB  - The sugar conformation of a DNA decamer was studied with proton-proton 3J
      coupling constants. Two samples, one comprising stereospecifically labeled 2'-R
      2H for all residues and the other 2'-S-2H, were prepared by the method of
      Kawashima et al. [J. Org. Chem. (1995) 60, 6980-6986; Nucleosides Nucleotides
      (1995) 14, 333-336], the deuterium labeling being highly stereospecific (> or =
      99% for all 2''-2H, > or = 98% for 2'-2H of A, C, and T, and > or = 93% for 2'-2H
      of G). The 3J values of all H1'-H2' and H1'-H2'' pairs, and several H2'-H3' and
      H2''-H3' pairs were determined by line fitting of 1D spectra with 0.1-0.2 Hz
      precision. The observed J coupling constants were explained by the rigid sugar
      conformation model, and the sugar conformations were found to be between C3'-exo
      and C2'-endo with phi(m) values of 26 degrees to 44 degrees, except for the
      second and 3' terminal residues C2 and C10. For the C2 and C10 residues, the
      lower fraction of S-type conformation was estimated from JH1'H2' and JH1'H2''
      values. For C10, the N-S two-site jump model or Gaussian distribution of the
      torsion angle model could explain the observed J values, and 68% S-type
      conformation or C1'-exo conformation with 27 degrees distribution was obtained,
      respectively. The differences between these two motional models are discussed
      based on a simple simulation of J-coupling constants.

PMID- 11246852
TI  - 15N NMR relaxation as a probe for helical intrinsic propensity: the case of the
      unfolded D2 domain of annexin I.
AB  - The isolated D2 domain of annexin I is unable to adopt a tertiary fold but
      exhibits both native and non-native residual structures. It thus constitutes an
      attractive model for the investigation of dynamics of partially folded states in
      the context of protein folding and stability. 15N relaxation parameters of the D2
      domain have been acquired at three different magnetic fields, 500, 600 and 800
      MHz. This enables the estimation of the contribution of conformational exchange
      to the relaxation parameters on the micro- to millisecond time scale, thus
      providing a suitable data set for the description of motions on the pico- and
      nanosecond time scale. The analysis of the seven spectral densities obtained
      (J(0), J(50 MHz), J(60 MHz), J(80 MHz), <J(500 MHz)>, <J(600 MHz)>, <J(800 MHz)>)
      provides complementary and meaningful results on the conformational features of
      the D2 domain structure previously depicted by chemical shift and NOE data.
      Especially, residual helix segments exhibit distinct dynamical behaviors that are
      related to their intrinsic helical propensity. Beside the spectral density
      analysis, a series of models derived from the Lipari and Szabo model-free
      approach are investigated. Two models containing three parameters are able to
      reproduce equally well the experimental data within experimental errors but
      provide different values of order parameters and correlation times. The inability
      to find a unique model to describe the data emphasizes the difficulty to use and
      interpret the model-free parameters in the case of partially or fully unfolded
      proteins consisting of a wide range of interconverting conformers.

PMID- 11246855
TI  - Simple multidimensional NMR experiments to obtain different types of one-bond
      dipolar couplings simultaneously.
AB  - In order to measure residual dipolar couplings, the molecule under study has to
      be partially oriented in the presence of the magnetic field. It has been observed
      that some protein samples are not stable under the conditions imposed by the
      orienting media. If different types of dipolar couplings are measured
      sequentially, their values will not agree with a unique alignment tensor that is
      changing slowly over time. This could bias the structure calculation. It would be
      more appropriate to obtain different types of dipolar couplings simultaneously,
      such that all the data correspond to one effective alignment tensor. We describe
      here a general NMR strategy designed to do so, that can be adapted to various
      existing pulse sequences.

PMID- 11246853
TI  - Enhanced loop DNA folding induced by thymine-CH3 group contact and perpendicular
      guanine-thymine interaction.
AB  - A remarkable stabilizing effect induced by T-CH3 group and perpendicular guanine
      thymine interactions in the DNA loop conformation has been demonstrated for the
      d(TTTG) loop structure using UV melting, high resolution NMR, distance geometry,
      and molecular dynamics studies. Contrary to the previously published d(TTCG)
      sequence that exhibits no specific inter-nucleotide interaction, we have found
      that d(TTTG), which differs only by one nucleotide with the d(TTCG) sequence (C7 
      -> T7), forms a rather stable and well-defined loop structure. Two characteristic
      structural features account for the stabilization of an otherwise flexible loop
      structure; the second loop T (T6) residue folds into the minor groove and engages
      in perpendicular interaction with the G8-NH2, while the third loop T (T7) residue
      stacks well upon the closing T5 x G8 wobble base pair and exhibits good contacts
      with many of the loop T5 and T6 sugar protons, which may form a hydrophobic core
      in the loop region. The importance of the bulky T7-CH3 was also proved by the UV
      melting study; while d(TTCG) hairpin exhibits a lower melting point (74.5 degrees
      C) than d(TTTG) hairpin (80.5 degrees C), d(TT(5-methyl)CG) hairpin resumes the
      same higher melting point (80 degrees C). Similarly, the fact that the melting
      temperature (74 degrees C) of d(TTTI) is lower than that of d(TTTG) indicates the
      critical role played by the G8-NH2 group. Our structural studies of the d(TTTG)
      loop indicate that DNA and RNA use a different strategy to establish stable
      tertiary folds. Comparison with several other pyrimidine-rich loop hairpins
      suggests that different minor-groove folding modes exist for the folding
      thymidine residue.

PMID- 11246856
TI  - Editing and diagonal peak suppression in three-dimensional HCCH protein NMR
      correlation experiments.
AB  - A novel three-dimensional (3D) HCCH NMR experiment is introduced. It involves 13C
      13C COSY or TOCSY coherence transfer plus two independent editing steps according
      to the number of protons attached to the individual carbons before and after the
      13C-13C homonuclear mixing. This double editing leads to simplification of HCCH
      protein side chain spectra that otherwise are prone to spectral overlap. Another
      interesting feature is amino acid selectivity, i.e. that the presence of certain
      correlations in a doubly edited HCCH subspectrum gives a clue as to assignment to
      a particular subgroup of amino acids or segments thereof. Finally, the selection
      of two different multiplicities in the two editing steps leads to diagonal peak
      suppression in the 1H-1H (3D spectrum recorded with two 1H and one 13C dimension)
      or the 13C-13C (3D spectrum recorded with one 1H and two 13C dimensions) two
      dimensional projection. The new experiment is demonstrated using a 13C,15N
      labeled protein sample, chymotrypsin inhibitor 2, at 500 MHz.

PMID- 11246854
TI  - Variability in automated assignment of NOESY spectra and three-dimensional
      structure determination: a test case on three small disulfide-bonded proteins.
AB  - Three independent runs of automatic assignment and structure calculations were
      performed on three small proteins, calcicludine from the venom of the green mamba
      Dendroaspis angusticeps, kappa-conotoxin PVIIA from the purple cone Conus
      purpurascens and HsTX1, a short scorpion toxin from the venom of Heterometrus
      spinnifer. At the end of all the runs, the number of cross peaks which remained
      unassigned (0.6%, 1.4% and 2% for calcicludine, kappa-conotoxin and HsTX1,
      respectively), as well as the number of constraints which were rejected as
      producing systematic violations (2.7%, 1.0%, and 1.4% for calcicludine, kappa
      conotoxin and HsTX1, respectively) were low. The conformation of the initial
      model used in the procedure (linear model or constructed by homology) has no
      influence on the final structures. Mainly two parameters control the procedure:
      the chemical shift tolerance and the cut-off distance. Independent runs of
      structure calculations, using the same parameters, yield structures for which the
      rmsd between averaged structures and the rmsd around each averaged structure were
      of the same order of magnitude. A different cut-off distance and a different
      chemical shift tolerance yield rmsd values on final average structures which did
      not differ more than 0.5 A compared to the rmsd obtained around the averaged
      structure for each calculation. These results show that the procedure is robust
      when applied to such a small disulfide-bonded protein.

PMID- 11246857
TI  - NMR structure of the pheromone Er-22 from Euplotes raikovi.

PMID- 11246858
TI  - NMR assignment of the A form of the pheromone-binding protein of Bombyx mori.

PMID- 11246859
TI  - Backbone (1H, 15N, 13C) resonance assignments of a 21 kDa construct of S. aureus
      peptide deformylase.

PMID- 11246860
TI  - Complete 1H, 15N, and 13C assignments of an exchangeable apolipoprotein, Locusta
      migratoria apolipophorin III.

PMID- 11246861
TI  - Assignment of 1H, 13C and 15N resonances of domain III of the ectodomain of
      apical membrane antigen 1 from Plasmodium falciparum.

PMID- 11246862
TI  - 1H, 15N and 13C resonance assignments and secondary structure determination of
      the RC-RNase 2 from oocytes of bullfrog Rana catesbeiana.

PMID- 11246863
TI  - 1H, 13C and 15N resonance assignment and secondary structure of Mycobacterium
      tuberculosis adenylate kinase.

PMID- 11246864
TI  - Assignment of 1H, 13C and 15N resonances to the sensory domain of the membraneous
      two-component fumarate sensor (histidine protein kinase) DcuS of Escherichia
      coli.

PMID- 11246865
TI  - Secondary structure and backbone resonance assignments for human interleukin-13.

PMID- 11246866
TI  - Defective function of Fas in patients with type 1 diabetes associated with other
      autoimmune diseases.
AB  - Fas (CD95) triggers programmed cell death and is involved in cell-mediated
      cytotoxicity and in shutting off the immune response. Inherited loss-of-function
      mutations hitting the Fas system cause the autoimmune/lymphoproliferative
      syndrome (ALPS). We have recently shown that ALPS patients' families display
      increased frequency of common autoimmune diseases, including type 1 diabetes.
      This work evaluates Fas function in type 1 diabetic patients without typical
      ALPS. Cell death induced by anti-Fas monoclonal antibody was investigated in T
      cells from 13 patients with type 1 diabetes alone and 19 patients with type 1
      diabetes plus other autoimmune diseases (IDDM-P). Moreover, we analyzed 19
      patients with thyroiditis alone (TYR), because most IDDM-P patients displayed
      thyroiditis. Frequency of resistance to Fas-induced cell death was significantly
      higher in patients with IDDM-P (73%) than in type 1 diabetic (23%) or TYR (16%)
      patients or in normal control subjects (3%). The defect was specific because
      resistance to methyl-prednisolone-induced cell death was not significantly
      increased in any group. Fas was always expressed at normal levels, and no Fas
      mutations were detected in four Fas-resistant IDDM-P patients. Analysis of the
      families of two Fas-resistant patients showing that several members were Fas
      resistant suggests that the defect has a genetic component. Moreover, somatic
      fusion of T-cells from Fas-resistant subjects and the Fas-sensitive HUT78 cell
      line generates Fas-resistant hybrid cells, which suggests that the Fas resistance
      is due to molecules exerting a dominant-negative effect on a normal Fas system.
      These data suggest that Fas defects may be a genetic factor involved in the
      development of polyreactive type 1 diabetes.

PMID- 11246867
TI  - Markedly decreased oxygen tension in transplanted rat pancreatic islets
      irrespective of the implantation site.
AB  - In this study, we syngeneically transplanted islets to three different
      implantation sites of diabetic and nondiabetic rats, then 9-12 weeks later we
      measured the blood perfusion and compared the tissue partial pressure of oxygen
      (PO2) levels of these transplanted islets to endogenous islets. Modified Clark
      microelectrodes (outer tip diameter 2-6 microm) were used for the oxygen tension
      measurements, and islet transplant blood perfusion was recorded by laser-Doppler
      flowmetry (probe diameter 0.45 mm). The islet graft blood perfusion was similar
      in all islet grafts, irrespective of the implantation site. In comparison, the
      three implantation organs (the kidney cortex, liver, and spleen) differed
      markedly in their blood perfusion. There were no differences in islet graft blood
      perfusion between diabetic and nondiabetic recipients. Within native pancreatic
      islets, the mean PO2 was approximately 40 mmHg; however, all transplanted islets
      had a mean PO2 of approximately 5 mmHg. The oxygen tension of the grafts did not
      differ among the implantation sites. In diabetic recipients, an even lower PO2
      level was recorded in the islet transplants. We conclude that the choice of
      implantation site seems less important than intrinsic properties of the
      transplanted islets with regard to the degree of revascularization and
      concomitant blood perfusion. Furthermore, the mean PO2 level in islets implanted
      to the kidney, liver, and spleen was markedly decreased at all three implantation
      sites when compared with native islets, especially in diabetic recipients. These
      results are suggestive of an insufficient oxygenization of revascularized
      transplanted islets, irrespective of the implantation site.

PMID- 11246868
TI  - Effects of kidney-pancreas transplantation on atherosclerotic risk factors and
      endothelial function in patients with uremia and type 1 diabetes.
AB  - Cardiovascular disease and the development of coronary artery disease play a
      pivotal role in increasing mortality in patients with type 1 diabetes. The aim of
      our study was to evaluate the effects of pancreas transplantation on
      atherosclerotic risk factors, endothelial-dependent dilation (EDD), and
      progression of intima media thickness (IMT) in patients with uremia and type 1
      diabetes after kidney-alone (KA) or kidney-pancreas (KP) transplantation. A cross
      sectional study comparing two groups of patients with type 1 diabetes was
      performed. Sixty patients underwent KP transplantation and 30 patients underwent
      KA transplantation. Age and cardiovascular risk profile were comparable in
      patients before transplantation. In all patients, atherosclerotic risks factors
      (lipid profile, fasting and post-methionine load plasma homocysteine, von
      Willebrand factor levels, D-dimer fragments, and fibrinogen) were assessed and
      Doppler echographic evaluation of IMT and endothelial function with flow-mediated
      and nitrate dilation of the brachial artery was performed. Twenty healthy
      subjects were chosen as controls (C) for EDD. Compared with patients undergoing
      KA transplantation, patients undergoing KP transplantation showed lower values
      for HbA1c (KP = 6.2 +/- 0.1% vs. KA = 8.4 +/- 0.5%; P < 0.01), fasting
      homocysteine (KP = 14.0 +/- 0.7 mcromol/l vs. KA = 19.0 +/- 2.0 micromol/l; P =
      0.02), von Willebrand factor levels (KP = 157.9 +/- 8.6% vs. KA = 212.5 +/-
      16.2%; P < 0.01), D-dimer fragments (KP = 0.29 +/- 0.02 microg/ml vs. KA = 0.73
      +/- 0.11 microg/ml;P < 0.01), fibrinogen (KP = 363.0 +/- 11.1 mg/dl vs. KA =
      397.6 +/- 19.4 mg/dl; NS), triglycerides (KP = 122.7 +/- 8.6 mg/dl vs. KA = 187.0
      +/- 30.1 mg/dl; P = 0.01), and urinary albumin excretion rate (KP = 13.5 +/- 1.9
      mg/24 h vs. KA = 57.3 +/- 26.3 mg/24 h; P < 0.01). Patients undergoing KP
      transplantation showed a normal EDD (KP = 6.21 +/- 2.42%, KA = 0.65 +/- 2.74%, C
      = 8.1 +/- 2.1%; P < 0.01), whereas no differences were observed in nitrate
      dependent dilation. Moreover, IMT was lower in patients undergoing KP
      transplantation than in patients undergoing KA transplantation (KP = 0.74 +/-
      0.03 mm vs. KA = 0.86 +/- 0.09 mm; P = 0.04). Our study showed that patients with
      type 1 diabetes have a lower atherosclerotic risk profile after KP
      transplantation than after KA transplantation. These differences are tightly
      correlated with metabolic control, fasting homocysteine levels, lower D-dimer
      fragments, and lower von Willebrand factor levels. Normal endothelial function
      and reduction of IMT was observed only in patients undergoing KP transplantation.

PMID- 11246869
TI  - Characterization of the mouse islet-specific glucose-6-phosphatase catalytic
      subunit-related protein gene promoter by in situ footprinting: correlation with
      fusion gene expression in the islet-derived betaTC-3 and hamster insulinoma tumor
      cell lines.
AB  - Glucose-6-phosphatase (G6Pase) is a multicomponent system located in the
      endoplasmic reticulum comprising a catalytic subunit and transporters for glucose
      6-phosphate, inorganic phosphate, and glucose. We have recently cloned a novel
      gene that encodes an islet-specific G6Pase catalytic subunit-related protein
      (IGRP) (Ebert et al., Diabetes 48:543-551, 1999). To begin to investigate the
      molecular basis for the islet-specific expression of the IGRP gene, a series of
      truncated IGRP-chloramphenicol acetyltransferase (CAT) fusion genes were
      transiently transfected into the islet-derived mouse betaTC-3 and hamster
      insulinoma tumor cell lines. In both cell lines, basal fusion gene expression
      decreased upon progressive deletion of the IGRP promoter sequence between -306
      and -66, indicating that multiple promoter regions are required for maximal IGRP
      CAT expression. The ligation-mediated polymerase chain reaction footprinting
      technique was then used to compare trans-acting factor binding to the IGRP
      promoter in situ in betaTC-3 cells, which express the endogenous IGRP gene, and
      adrenocortical Y1 cells, which do not. Multiple trans-acting factor binding sites
      were selectively identified in betaTC-3 cells that correlate with regions of the
      IGRP promoter identified as being required for basal IGRP-CAT fusion gene
      expression. The data suggest that hepatocyte nuclear factor 3 may be important
      for basal IGRP gene expression, as it is for glucagon, GLUT2, and Pdx-1 gene
      expression. In addition, binding sites for several trans-acting factors not
      previously associated with islet gene expression, as well as binding sites for
      potentially novel proteins, were identified.

PMID- 11246870
TI  - Efficient ex vivo transduction of pancreatic islet cells with recombinant adeno
      associated virus vectors.
AB  - The ability to transfer immunoregulatory, cytoprotective, or antiapoptotic genes
      into pancreatic islet cells may allow enhanced posttransplantation survival of
      islet allografts and inhibition of recurrent autoimmune destruction of these
      cells in type 1 diabetes. However, transient transgene expression and the
      tendency to induce host inflammatory responses have limited previous gene
      delivery studies using viral transfer vectors. We demonstrate here that
      recombinant adeno-associated virus (rAAV) serotype 2, a vector that can overcome
      these limitations, effectively transduces both human and murine pancreatic islet
      cells with reporter genes as well as potentially important immunoregulatory
      cytokine genes (interleukin-4, interleukin-10), although a very high multiplicity
      of infection (10,000 infectious units/islet equivalent) was required. This
      requirement was alleviated by switching to rAAV serotype 5, which efficiently
      transduced islets at a multiplicity of infection of 100. Although adenovirus (Ad)
      coinfection was required for efficient ex vivo expression at early time points,
      islets transduced without Ad expressed efficiently when they were transplanted
      under the renal capsule and allowed to survive in vivo. The rAAV-delivered
      transgenes did not interfere with islet cell insulin production and were
      expressed in both beta- and non-beta-cells. We believe rAAV will provide a useful
      tool to deliver therapeutic genes for modulating immune responses against islet
      cells and markedly enhance longterm graft survival.

PMID- 11246871
TI  - Multipotential nestin-positive stem cells isolated from adult pancreatic islets
      differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic
      phenotypes.
AB  - The endocrine cells of the rat pancreatic islets of Langerhans, including insulin
      producing beta-cells, turn over every 40-50 days by processes of apoptosis and
      the proliferation and differentiation of new islet cells (neogenesis) from
      progenitor epithelial cells located in the pancreatic ducts. However, the
      administration to rats of islet trophic factors such as glucose or glucagon-like
      peptide 1 for 48 h results in a doubling of islet cell mass, suggesting that
      islet progenitor cells may reside within the islets themselves. Here we show that
      rat and human pancreatic islets contain a heretofore unrecognized distinct
      population of cells that express the neural stem cell-specific marker nestin.
      Nestin-positive cells within pancreatic islets express neither the hormones
      insulin, glucagon, somatostatin, or pancreatic polypeptide nor the markers of
      vascular endothelium or neurons, such as collagen IV and galanin. Focal regions
      of nestin-positive cells are also identified in large, small, and centrolobular
      ducts of the rat pancreas. Nestin-positive cells in the islets and in pancreatic
      ducts are distinct from ductal epithelium because they do not express the ductal
      marker cytokeratin 19 (CK19). After their isolation, these nestin-positive cells
      have an unusually extended proliferative capacity when cultured in vitro
      (approximately 8 months), can be cloned repeatedly, and appear to be
      multipotential. Upon confluence, they are able to differentiate into cells that
      express liver and exocrine pancreas markers, such as alpha-fetoprotein and
      pancreatic amylase, and display a ductal/endocrine phenotype with expression of
      CK19, neural-specific cell adhesion molecule, insulin, glucagon, and the
      pancreas/duodenum specific homeodomain transcription factor, IDX-1. We propose
      that these nestin-positive islet-derived progenitor (NIP) cells are a distinct
      population of cells that reside within pancreatic islets and may participate in
      the neogenesis of islet endocrine cells. The NIP cells that also reside in the
      pancreatic ducts may be contributors to the established location of islet
      progenitor cells. The identification of NIP cells within the pancreatic islets
      themselves suggest possibilities for treatment of diabetes, whereby NIP cells
      isolated from pancreas biopsies could be expanded ex vivo and transplanted into
      the donor/recipient.

PMID- 11246872
TI  - The prohormone convertase enzyme 2 (PC2) is essential for processing pro-islet
      amyloid polypeptide at the NH2-terminal cleavage site.
AB  - Impaired processing of pro-islet amyloid polypeptide (proIAPP), the precursor of
      the beta-cell peptide islet amyloid polypeptide (IAPP) (amylin), has been
      implicated in islet amyloid formation in type 2 diabetes. The prohormone
      convertase enzymes PC3 (also known as PC1) and PC2 are localized to beta-cell
      secretory granules with proIAPP and proinsulin and are responsible for proinsulin
      processing. To determine whether PC2 might be essential for proIAPP processing,
      we performed Western blot analysis of freshly isolated islets from normal mice
      and mice lacking active PC2. As expected, the primary species of IAPP
      immunoreactivity in islets from wild-type mice was fully processed (4-kDa) IAPP,
      with only small amounts of the 8-kDa precursor (unprocessed proIAPP) present.
      Islets from heterozygous PC2 null mice were identical to wild-type animals,
      suggesting that half the normal complement of PC2 is sufficient for normal
      proIAPP processing. By contrast, in islets from homozygous PC2 null mice, the
      predominant IAPP-immunoreactive form was of intermediate size (approximately 6
      kDa), with no detectable mature IAPP and slightly elevated amounts of the 8-kDa
      precursor form present. Thus, in the absence of PC2, proIAPP processing appears
      to be blocked at the level of a proIAPP conversion intermediate.
      Immunofluorescence of pancreas sections and immunoblotting using antisera raised
      to the NH2- and COOH-terminal flanking regions of mouse proIAPP demonstrated that
      the 6-kDa intermediate form was an NH2-terminally extended proIAPP conversion
      intermediate (processed only at the COOH-terminus). These data indicate that PC2
      is essential for processing of proIAPP at the NH2-terminal cleavage site in vivo
      and that PC3 is likely only capable of processing proIAPP at the COOH-terminal
      cleavage site.

PMID- 11246874
TI  - Distinction between interleukin-1-induced necrosis and apoptosis of islet cells.
AB  - Interleukin (IL)-1beta is known to cause beta-cell death in isolated rat islets.
      This effect has been attributed to induction of nitric oxide (NO) synthase in
      beta-cells and subsequent generation of toxic NO levels; it was not observed,
      however, in dispersed rat beta-cells. The present study demonstrates that IL
      1beta induces NO-dependent necrosis in rat beta-cells cultured for 3 days at high
      cell density or in cell aggregates but not as single cells. Its cytotoxic
      condition is not explained by higher NO production rates but might result from
      higher intercellular NO concentrations in statically cultured cell preparations
      with cell-to-cell contacts; nitrite levels in collected culture medium are not a
      reliable index for these intercellular concentrations. Absence of IL-1-induced
      necrosis in rat alpha-cells or in human beta-cells is attributed to the
      cytokine's failure to generate NO in these preparations, not to their reduced
      sensitivity to NO: the NO donor GEA 3162 (15 min, 50-100 micromol/l) exerts a
      comparable necrotic effect in rat and human alpha- or beta-cells. In preparations
      in which IL-1beta does not cause beta-cell necrosis, its combination with gamma
      interferon (IFN-gamma) results in NO-independent apoptosis, starting after 3 days
      and increasing with the duration of exposure. Because IFN-gamma alone was
      apoptotic for rat alpha-cells, it is proposed that IL-1beta can make beta-cells
      susceptible to this effect, conceivably through altering their phenotype. It is
      concluded that IL-1beta can cause NO-dependent necrosis or NO-independent
      apoptosis of islet cells, depending on the species and on the environmental
      conditions. The experiments in isolated human beta-cell preparations suggest that
      these cells may preferentially undergo apoptosis when exposed to IL-1beta plus
      IFN-gamma unless neighboring non-beta-cells produce toxic NO levels.

PMID- 11246873
TI  - Measurements of cytoplasmic Ca2+ in islet cell clusters show that glucose rapidly
      recruits beta-cells and gradually increases the individual cell response.
AB  - The proportion of isolated single beta-cells developing a metabolic,
      biosynthetic, or secretory response increases with glucose concentration
      (recruitment). It is unclear whether recruitment persists in situ when beta-cells
      are coupled. We therefore measured the cytoplasmic free Ca2+ correction ([Ca2+]i)
      (the triggering signal of glucose-induced insulin secretion) in mouse islet
      single cells or clusters cultured for 1-2 days. In single cells, the threshold
      glucose concentration ranged between 6 and 10 mmol/l, at which concentration a
      maximum of approximately 65% responsive cells was reached. Only 13% of the cells
      did not respond to glucose plus tolbutamide. The proportion of clusters showing a
      [Ca2+]i rise increased from approximately 20 to 95% between 6 and 10 mmol/l
      glucose, indicating that the threshold sensitivity to glucose differs between
      clusters. Within responsive clusters, 75% of the cells were active at 6 mmol/l
      glucose and 95-100% at 8-10 mmol/l glucose, indicating that individual cell
      recruitment is not prominent within clusters; in clusters responding to glucose,
      all or almost all cells participated in the response. Independently of cell
      recruitment, glucose gradually augmented the magnitude of the average [Ca2+]i
      rise in individual cells, whether isolated or associated in clusters. When
      insulin secretion was measured simultaneously with [Ca2+]i, a good temporal and
      quantitative correlation was found between both events. However, beta-cell
      recruitment was maximal at 10 mmol/l glucose, whereas insulin secretion increased
      up to 15-20 mmol/l glucose. In conclusion, beta-cell recruitment by glucose can
      occur at the stage of the [Ca2+]i response. However, this type of recruitment is
      restricted to a narrow range of glucose concentrations, particularly when beta
      cell association decreases the heterogeneity of the responses. Glucose-induced
      insulin secretion by islets, therefore, cannot entirely be ascribed to
      recruitment of beta-cells to generate a [Ca2+]i response. Modulation of the
      amplitude of the [Ca2+]i response and of the action of Ca2+ on exocytosis
      (amplifying actions of glucose) may be more important.

PMID- 11246875
TI  - Effect of vagal cooling on the counterregulatory response to hypoglycemia induced
      by a low dose of insulin in the conscious dog.
AB  - We previously demonstrated, using a nerve-cooling technique, that the vagus
      nerves are not essential for the counterregulatory response to hypoglycemia
      caused by high levels of insulin. Because high insulin levels per se augment the
      central nervous system response to hypoglycemia, the question arises whether
      afferent nerve fibers traveling along the vagus nerves would play a role in the
      defense of hypoglycemia in the presence of a more moderate insulin level. To
      address this issue, we studied two groups of conscious 18-h-fasted dogs with
      cooling coils previously placed on both vagus nerves. Each study consisted of a
      100-min equilibration period, a 40-min basal period, and a 150-min hypoglycemic
      period. Glucose was lowered using a glycogen phosphorylase inhibitor and a low
      dose of insulin infused into the portal vein (0.7 mU.kg(-1) min(-1)). The
      arterial plasma insulin level increased to 15 +/- 2 microU/ml and the plasma
      glucose level fell to a plateau of 57 +/- 3 mg/dl in both groups. The vagal
      cooling coils were perfused with a 37 degrees C (SHAM COOL; n = 7) or a -20
      degrees C (COOL; n = 7) ethanol solution for the last 90 min of the study to
      block parasympathetic afferent fibers. Vagal cooling caused a marked increase in
      the heart rate and blocked the hypoglycemia-induced increase in the arterial
      pancreatic polypeptide level. The average increments in glucagon (pg/ml),
      epinephrine (pg/ml), norepinephrine (pg/ml), cortisol (microg/dl), glucose
      production (mg.kg(-1). min(-1)), and glycerol (micromol/l) in the SHAM COOL group
      were 53 +/- 9, 625 +/- 186, 131 +/- 48, 4.63 +/- 1.05, -0.79 +/- 0.24, and 101 +/
      18, respectively, and in the COOL group, the increments were 39 +/- 7, 837 +/-
      235, 93 +/- 39, 6.28 +/- 1.03 (P < 0.05), -0.80 +/- 0.20, and 73 +/- 29,
      respectively. Based on these data, we conclude that, even in the absence of high
      insulin concentrations, afferent signaling via the vagus nerves is not required
      for a normal counterregulatory response to hypoglycemia.

PMID- 11246876
TI  - Effect of glucagon-like peptide-1(7-36)-amide on initial splanchnic glucose
      uptake and insulin action in humans with type 1 diabetes.
AB  - In vitro studies indicate that glucagon-like peptide-1(7-36)-amide (GLP-1) can
      enhance hepatic glucose uptake. To determine whether GLP-1 increases splanchnic
      glucose uptake in humans, we studied seven subjects with type 1 diabetes on two
      occasions. On both occasions, glucose was maintained at approximately 5.5 mmo/l
      during the night using a variable insulin infusion. On the morning of the study,
      a somatostatin, glucagon, and growth hormone infusion was started to maintain
      basal hormone levels. Glucose (containing [3H]glucose) was infused via an
      intraduodenal tube at a rate of 20 micromol.kg(-1).min(-1). Insulin
      concentrations were increased to approximately 500 pmol/l while glucose was
      clamped at approximately 8.8 mmol/l for the next 4 h by means of a variable
      intravenous glucose infusion labeled with [6,6-2H2]glucose. Surprisingly, the
      systemic appearance of intraduodenally infused glucose was higher (P = 0.01)
      during GLP-1 infusion than saline infusion, indicating a lower (P < 0.05) rate of
      initial splanchnic glucose uptake (1.4 +/- 1.5 vs. 4.8 +/- 0.8 micromol.kg(
      1).min(-1)). On the other hand, flux through the hepatic uridine-diphosphate-
      glucose pool did not differ between study days (14.2 +/- 5.5 vs. 13.0 +/- 4.2
      micromol.kg(-1).min(-1)), implying equivalent rates of glycogen synthesis. GLP-1
      also impaired (P < 0.05) insulin-induced suppression of endogenous glucose
      production (6.9 +/- 2.9 vs. 1.3 +/- 1.4 micromol.kg(-1).min(-1)), but caused a
      time-dependent increase (P < 0.01) in glucose disappearance (93.7 +/- 10.0 vs.
      69.3 +/- 6.3 micromol.kg(-1).min(-1); P < 0.01) that was evident only during the
      final hour of study. We conclude that in the presence of hyperglycemia,
      hyperinsulinemia, and enterally delivered glucose, GLP-1 increases total body but
      not splanchnic glucose uptake in humans with type 1 diabetes.

PMID- 11246878
TI  - Cellular mechanism of nutritionally induced insulin resistance in Psammomys
      obesus: overexpression of protein kinase Cepsilon in skeletal muscle precedes the
      onset of hyperinsulinemia and hyperglycemia.
AB  - The sand rat (Psammomys obesus) is an animal model of nutritionally induced
      diabetes. We report here that several protein kinase C (PKC) isoforms (alpha,
      epsilon, and zeta, representing all three subclasses of PKC) are overexpressed in
      the skeletal muscle of diabetic animals of this species. This is most prominent
      for the epsilon isotype of PKC. Interestingly, increased expression of PKCepsilon
      could already be detected in normoinsulinemic, normoglycemic (prediabetic)
      animals of the diabetes-prone (DP) line when compared with a diabetes-resistant
      (DR) line. In addition, plasma membrane (PM)-associated fractions of PKCalpha and
      PKCepsilon were significantly increased in skeletal muscle of diabetic animals,
      suggesting chronic activation of these PKC isotypes in the diabetic state. The
      increased PM association of these PKC isotypes revealed a significant correlation
      with the diacylglycerol content in the muscle samples. Altered
      expression/activity of PKCepsilon, in particular, may thus contribute to the
      development of diabetes in these animals; along with other PKC isotypes, it may
      be involved in the progression of the disease. This may possibly occur through
      inhibition of insulin receptor (IR) tyrosine kinase activity mediated by
      serine/threonine phosphorylation of the IR or insulin receptor substrate 1 (IRS
      1). However, overexpression of PKCepsilon also mediated down-regulation of IR
      numbers in a cell culture model (HEK293), resulting in attenuation of insulin
      downstream signaling (reduced protein kinase B [PKB]/Akt activity). In accordance
      with this, we detected decreased 125I-labeled insulin binding, probably
      reflecting a downregulation of IR numbers, in skeletal muscle of Psammomys
      animals from the DP line. The number of IRs was inversely correlated to both the
      expression and PM-associated levels of PKCepsilon. These data suggest that
      overexpression of PKCepsilon may be causally related to the development of
      insulin resistance in these animals, possibly by increasing the degradation of
      IRs.

PMID- 11246877
TI  - Insulin resistance with enhanced insulin signaling in high-salt diet-fed rats.
AB  - Previous clinical studies showed an apparent correlation between hypertension and
      insulin resistance, and patients with diabetes are known to have increased blood
      pressure responsiveness to salt loading. To investigate the effect of high salt
      intake on insulin sensitivity and the insulin signaling pathway, a high-salt diet
      (8% NaCl) or a normal diet was given to 7-week-old SD rats for 2 weeks. High salt
      fed rats developed slightly but significantly higher systolic blood pressure than
      controls (133 +/- 2 vs. 117 +/- 2 mmHg, P < 0.001), with no change in food intake
      or body weight. High salt-fed rats were slightly hyperglycemic (108.5 +/- 2.8 vs.
      97.8 +/- 2.5 mg/dl, P = 0.01) and slightly hyperinsulinemic (0.86 +/- 0.07 vs.
      0.61 +/- 0.06 ng/ml, P = 0.026) in the fasting condition, as compared with
      controls. Hyperinsulinemic-euglycemic clamp study revealed a 52.7% decrease in
      the glucose infusion rate and a 196% increase in hepatic glucose production in
      high salt-fed rats, which also showed a 66.4% decrease in 2-deoxyglucose uptake
      into isolated skeletal muscle and a 44.5% decrease in insulin-induced glycogen
      synthase activation in liver, as compared with controls. Interestingly, despite
      the presence of insulin resistance, high salt-fed rats showed enhanced insulin
      induced tyrosine phosphorylation of insulin receptor substrate (IRS)-1, IRS-2
      (liver and muscle), and IRS-3 (liver only). Phosphatidylinositol (PI) 3-kinase
      activities associated with IRS and phosphotyrosine in the insulin-stimulated
      condition increased 2.1- to 4.1-fold, as compared with controls. Insulin-induced
      phosphorylation of Ser-473 of Akt and Ser-21 of glycogen synthase kinase-3 also
      increased 2.9- and 2-fold, respectively, in the liver of the high salt-fed rats.
      Therefore, in both the liver and muscle of high salt-fed rats, intracellular
      insulin signaling leading to PI 3-kinase activation is enhanced and insulin
      action is attenuated. The hyperinsulinemic-euglycemic clamp study showed that
      decreased insulin sensitivity induced with a high-salt diet was not reversed by
      administration of pioglitazone. The following can be concluded: 1) a high-salt
      diet may be a factor promoting insulin resistance, 2) the insulin-signaling step
      impaired by high salt intake is likely to be downstream from PI 3-kinase or Akt
      activation, and 3) this unique insulin resistance mechanism may contribute to the
      development of diabetes in patients with hypertension.

PMID- 11246880
TI  - Preferential channeling of energy fuels toward fat rather than muscle during high
      free fatty acid availability in rats.
AB  - The preferential channeling of different fuels to fat and changes in the
      transcription profile of adipose tissue and skeletal muscle are poorly understood
      processes involved in the pathogenesis of obesity and insulin resistance.
      Carbohydrate and lipid metabolism may play relevant roles in this context. Freely
      moving lean Zucker rats received 3- and 24-h infusions of Intralipid (Pharmacia
      and Upjohn, Milan, Italy) plus heparin, or saline plus heparin, to evaluate how
      an increase in free fatty acids (nonesterified fatty acid [NEFA]) modulates fat
      tissue and skeletal muscle gene expression and thus influences fuel partitioning.
      Glucose uptake was determined in various tissues at the end of the infusion
      period by means of the 2-deoxy-[1-3H]-D-glucose technique after a euglycemic
      hyperinsulinemic clamp: high NEFA levels markedly decreased insulin-mediated
      glucose uptake in red fiber-type muscles but enhanced glucose utilization in
      visceral fat. Using reverse transcriptase-polymerase chain reaction and Northern
      blotting analyses, the mRNA expression of fatty acid translocase (FAT)/CD36,
      GLUT4, tumor necrosis factor (TNF)-alpha, peroxisome proliferator-activated
      receptor (PPAR)-gamma, leptin, uncoupling protein (UCP)-2, and UCP-3 was
      investigated in different fat depots and skeletal muscles before and after the
      study infusions. GLUT4 mRNA levels significantly decreased (by approximately 25%)
      in red fiber-type muscle (soleus) and increased (by approximately 45%) in
      visceral adipose tissue. Furthermore, there were marked increases in FAT/CD36,
      TNF-alpha, PPAR-gamma, leptin, UCP2, and UCP3 mRNA levels in the visceral fat and
      muscle of the treated animals in comparison with those measured in the saline
      treated animals. These data suggest that the in vivo gene expression of FAT/CD36,
      GLUT4, TNF-alpha, PPAR-gamma, leptin, UCP2, and UCP3 in visceral fat and red
      fiber-type muscle are differently regulated by circulating lipids and that
      selective insulin resistance seems to favor, at least in part, a prevention of
      fat accumulation in tissues not primarily destined for fat storage, thus
      contributing to increased adiposity and the development of a prediabetic
      syndrome.

PMID- 11246879
TI  - GLUT4 overexpression in db/db mice dose-dependently ameliorates diabetes but is
      not a lifelong cure.
AB  - We previously reported that overexpression of GLUT4 in lean, nondiabetic
      C57BL/KsJ-lepr(db/+) (db/+) mice resulted in improved glucose tolerance
      associated with increased basal and insulin-stimulated glucose transport in
      isolated skeletal muscle. We used the diabetic (db/db) litter mates of these mice
      to examine the effects of GLUT4 overexpression on in vivo glucose utilization and
      on in vitro glucose transport and GLUT4 translocation in diabetic mice. We
      examined in vivo glucose disposal by oral glucose challenge and hyperinsulinemic
      hyperglycemic clamps. We also evaluated the in vitro relationship between glucose
      transport activity and cell surface GLUT4 levels as assessed by photolabeling
      with the membrane-impermeant reagent 2-N-(4-(1-azi-2,2,2-trifluoroethyl)benzoyl)
      1,3-bis(D-mannose-4-yloxy)-2-propylamine in extensor digitorum longus (EDL)
      muscles. All parameters were examined as functions of animal age and the level of
      GLUT4 overexpression. In young mice (age 10-12 weeks), both lower (two- to
      threefold) and higher (four- to fivefold) levels of GLUT4 overexpression were
      associated with improved glucose tolerance compared to age-matched nontransgenic
      (NTG) mice. However, glucose tolerance deteriorated with age in db/db mice,
      although less rapidly in transgenic mice expressing the higher level of GLUT4.
      Glucose infusion rates during hyperinsulinemic-hyperglycemic clamps were
      increased with GLUT4 overexpression, compared with NTG mice in both lower and
      higher levels of GLUT4 overexpression, even in the older mice. Surprisingly,
      isolated EDL muscles from diabetic db/db mice did not exhibit alterations in
      either basal or insulin-stimulated glucose transport activity or cell surface
      GLUT4 compared to nondiabetic db/+ mice. Furthermore, both GLUT4 overexpression
      levels and animal age are associated with increased basal and insulin-stimulated
      glucose transport activities and cell surface GLUT4. However, the observed
      increased glucose transport activity in older db/db mice was not accompanied by
      an equivalent increase in cell surface GLUT4 compared to younger animals. Thus,
      although in vivo glucose tolerance is improved with GLUT4 overexpression in young
      animals, it deteriorates with age; in contrast, insulin responsiveness as
      assessed by the clamp technique remains improved with GLUT4 overexpression, as
      does in vitro insulin action. In summary, despite an impairment in whole-body
      glucose tolerance, skeletal muscle of the old transgenic GLUT4 db/db mice is
      still insulin responsive in vitro and in vivo.

PMID- 11246881
TI  - Reduced postprandial concentrations of intact biologically active glucagon-like
      peptide 1 in type 2 diabetic patients.
AB  - Incretin hormones importantly enhance postprandial insulin secretion but are
      rapidly degraded to inactive metabolites by ubiquitous dipeptidyl peptidase IV.
      The concentrations of the intact biologically active hormones remain largely
      unknown. Using newly developed assays for intact glucagon-like peptide (GLP)-1
      and glucose-dependent insulinotropic polypeptide (GIP), we measured plasma
      concentrations after a mixed breakfast meal (566 kcal) in 12 type 2 diabetic
      patients (age 57 years [range 49-67], BMI 31 kg/m2 [27-38], and HbA1c 9.2% [7.0
      12.5]) and 12 matched healthy subjects. The patients had fasting hyperglycemia
      (10.7 mmol/l [8.0-14.8]) increasing to 14.6 mmol/l (11.5-21.5) 75 min after meal
      ingestion. Fasting levels of insulin and C-peptide were similar to those of the
      healthy subjects, but the postprandial responses were reduced and delayed.
      Fasting levels and meal responses were similar between patients and healthy
      subjects for total GIP (intact + metabolite) as well as intact GIP, except for a
      small decrease in the patients at 120 min; integrated areas for intact hormone
      (area under the curve [AUC]INT) averaged 52 +/- 4% (for patients) versus 56 +/-
      3% (for control subjects) of total hormone AUC (AUC(TOT)). AUC(INT) for GLP-1
      averaged 48 +/- 2% (for patients) versus 51 +/- 5% (for control subjects) of
      AUC(TOT). AUC(TOT) for GLP-1 as well as AUC(INT) tended to be reduced in the
      patients (P = 0.2 and 0.07, respectively); but the profile of the intact GLP-1
      response was characterized by a small early rise (30-45 min) and a significantly
      reduced late phase (75-150 min) (P < 0.02). The measurement of intact incretin
      hormones revealed that total as well as intact GIP responses were minimally
      decreased in patients with type 2 diabetes, whereas the late intact GLP-1
      response was strongly reduced, supporting the hypothesis that an impaired
      function of GLP-1 as a transmitter in the enteroinsular axis contributes to the
      inappropriate insulin secretion in type 2 diabetes.

PMID- 11246882
TI  - A genome-wide scan for abdominal fat assessed by computed tomography in the
      Quebec Family Study.
AB  - To identify chromosomal regions harboring genes influencing the propensity to
      store fat in the abdominal area, a genome-wide scan for abdominal fat was
      performed in the Quebec Family Study. Cross-sectional areas of the amount of
      abdominal total fat (ATF) and abdominal visceral fat (AVF) were assessed from a
      computed tomography scan taken at L4-L5 in 521 adult subjects. Abdominal
      subcutaneous fat (ASF) was obtained by computing the difference between ATF and
      AVF. The abdominal fat phenotypes were adjusted for age and sex effects as well
      as for total amount of body fat (kilogram of fat mass) measured by underwater
      weighing, and the adjusted phenotypes were used in linkage analyses. A total of
      293 microsatellite markers spanning the 22 autosomal chromosomes were typed. The
      average intermarker distance was 11.9 cM. A maximum of 271 sib-pairs were
      available for single-point (SIBPAL) and 156 families for multipoint variance
      components (SEGPATH) linkage analyses. The strongest evidence of linkage was
      found on chromosome 12q24.3 between marker D12S2078 and ASF (logarithm of odds
      [LOD] = 2.88). Another marker (D12S1045) located within 2 cM of D12S2078 also
      provided evidence of sib-pair linkage with ASF (P = 0.019), ATF (P = 0.015), and
      AVF (P = 0.0007). Other regions with highly suggestive evidence (P < 0.0023 or
      LOD > or =1.75) of multipoint linkage and evidence (P < 0.05) of single-point
      linkage, all for ASF, included chromosomes 1p11.2, 4q32.1, 9q22.1, 12q22-q23, and
      17q21.1. Three of these loci (1p11.2, 9q22.1, and 17q21.1) are close to genes
      involved in the regulation of sex steroid levels, whereas two others (4q32.1 and
      17q21.1) are in the proximity of genes involved in the regulation of food intake.
      This first genome-wide scan for abdominal fat assessed by computed tomography
      indicates that there may be several loci determining the propensity to store fat
      in the abdominal depot and that some of these loci may influence the development
      of diabetes in obese subjects.

PMID- 11246883
TI  - Glucokinase gene locus transgenic mice are resistant to the development of
      obesity-induced type 2 diabetes.
AB  - Transgenic mice that overexpress the entire glucokinase (GK) gene locus have been
      previously shown to be mildly hypoglycemic and to have improved tolerance to
      glucose. To determine whether increased GK might also prevent or diminish
      diabetes in diet-induced obese animals, we examined the effect of feeding these
      mice a high-fat high-simple carbohydrate low-fiber diet (HF diet) for 30 weeks.
      In response to this diet, both normal and transgenic mice became obese and had
      similar BMIs (5.3 +/- 0.1 and 5.0 +/- 0.1 kg/m2 in transgenic and non-transgenic
      mice, respectively). The blood glucose concentration of the control mice
      increased linearly with time and reached 17.0 +/- 1.3 mmol/l at the 30th week. In
      contrast, the blood glucose of GK transgenic mice rose to only 9.7 +/- 1.2 mmol/l
      at the 15th week, after which it returned to 7.6 +/- 1.0 mmol/l by the 30th week.
      The plasma insulin concentration was also lower in the GK transgenic animals (232
      +/- 79 pmol/l) than in the controls (595 +/- 77 pmol/l), but there was no
      difference in plasma glucagon concentrations. Together, these data indicate that
      increased GK levels dramatically lessen the development of both hyperglycemia and
      hyperinsulinemia associated with the feeding of an HF diet.

PMID- 11246884
TI  - Autonomic neuropathy in nondiabetic offspring of type 2 diabetic subjects is
      associated with urinary albumin excretion rate and 24-h ambulatory blood
      pressure: the Fredericia Study.
AB  - The aim of this study was to examine the impact of parental type 2 diabetes on
      the autonomic nervous system and to determine whether autonomic neuropathy is
      present and associated with changes in 24-h ambulatory blood pressure (AMBP) and
      urinary albumin excretion rate (UAER) in nondiabetic subjects with parental type
      2 diabetes. We examined 223 nondiabetic offspring of type 2 diabetic subjects and
      a control group of 258 offspring of nondiabetic subjects. The autonomic nervous
      system was assessed by three cardiovascular reflex tests, 24-h AMBP was measured
      with an oscillometric recorder (90207; Spacelabs, Redmond, WA), and UAER was
      determined through three overnight urine samples. The subjects with parental type
      2 diabetes had significantly lower heart rate variation in all three bedside
      tests (P < 0.01) than subjects without parental diabetes. The prevalence of
      autonomic neuropathy in the nondiabetic offspring with parental type 2 diabetes
      (6.7%) was significantly (P < 0.01) higher compared with the control group
      (1.6%). Autonomic neuropathy was associated with a higher fasting insulin level
      (P < 0.05), higher UAER (P < 0.001), higher 24-h mean AMBP (P < 0.01), and
      reduced diurnal blood pressure variation (P < 0.001) after adjustment for age,
      sex, and BMI. In conclusion, parental type 2 diabetes was found to be associated
      with alterations in the autonomic nervous system in nondiabetic subjects. The
      presence of autonomic neuropathy in subjects with parental type 2 diabetes was
      associated with higher UAER, fasting insulin level, and 24-h AMBP and a reduced
      diurnal blood pressure variation. This study indicates that parental type 2
      diabetes has an impact on the cardiac autonomic function in nondiabetic subjects.

PMID- 11246885
TI  - A polymorphism in the gene for IGF-I: functional properties and risk for type 2
      diabetes and myocardial infarction.
AB  - Evidence is accumulating that low levels of IGF-I play a role in the pathogenesis
      of type 2 diabetes and cardiovascular diseases. We examined the role of a genetic
      polymorphism in the promoter region of the IGF-I gene in relation to circulating
      IGF-I levels and growth measured as body height, and we studied the relationship
      of this polymorphism with type 2 diabetes and myocardial infarction. The relation
      between the IGF-I polymorphism and body height was assessed in a population-based
      sample of 900 subjects from the Rotterdam Study. Within each genotype stratum, 50
      subjects were randomly selected for a study of the relation of this polymorphism
      with serum IGF-I levels. To assess the risk for type 2 diabetes, we studied 220
      patients and 596 normoglycemic control subjects. For myocardial infarction, 477
      patients with evidence of myocardial infarction on electrocardiogram and 808
      control subjects were studied. A 192-bp allele was present in 88% of the
      population, suggesting that this is the wild-type allele from which all other
      alleles originated. Body height was, on average, 2.7 cm lower (95% CI for
      difference -4.6 to -0.8 cm, P = 0.004), and serum IGF-I concentrations were 18%
      lower (95% CI for difference -6.0 to -1.3 mmol/l, P = 0.003) in subjects who did
      not carry the 192-bp allele. In noncarriers of the 192-bp allele, an increased
      relative risk for type 2 diabetes (1.7 [95% CI 1.1-2.7]) and for myocardial
      infarction (1.7 [95% CI 1.1-2.5]) was found. In patients with type 2 diabetes,
      the relative risk for myocardial infarction in subjects without the 192-bp allele
      was 3.4 (95% CI 1.1-11.3). Our study suggests that a genetically determined
      exposure to relatively low IGF-I levels is associated with an increased risk for
      type 2 diabetes and myocardial infarction.

PMID- 11246886
TI  - Studies with apolipoprotein A-II transgenic mice indicate a role for HDLs in
      adiposity and insulin resistance.
AB  - Apolipoprotein A-II (apoA-II) is the second most abundant protein in HDLs.
      Genetic studies in humans have provided evidence of linkage of the apoA-II gene
      locus to plasma free fatty acid (FFA) levels and to type 2 diabetes, and
      transgenic mice overexpressing mouse apoA-II have elevated levels of both FFA and
      triglycerides. We now show that apoA-II promotes insulin resistance and has
      diverse effects on fat homeostasis. ApoA-II transgenic mice have increased
      adipose mass and higher plasma leptin levels than C57BL/6J control mice. Fasting
      glucose levels were similar between apoA-II transgenic and control mice, but
      plasma insulin levels were elevated approximately twofold in the apoA-II
      transgenic mice. Compared with control mice, apoA-II transgenic mice exhibited a
      delay in plasma clearance of a glucose bolus. Adipose tissue isolated from fasted
      apoA-II transgenic mice exhibited a 50% decrease in triglyceride hydrolysis
      compared with adipose tissue from control mice. This is consistent with a normal
      response of adipose tissue to the increased insulin levels in the apoA-II
      transgenic mice and may partially explain the increased fat deposition. Skeletal
      muscle isolated from fasted apoA-II transgenic mice exhibited reduced uptake of 2
      deoxyglucose compared with muscles isolated from control mice. Our observations
      indicate that a primary disturbance in lipoprotein metabolism can result in
      several traits associated with insulin resistance, consistent with the hypothesis
      that insulin resistance and type 2 diabetes can, under certain circumstances, be
      related primarily to altered lipid metabolism rather than glucose metabolism.

PMID- 11246887
TI  - Lipid transfer protein activities in type 1 diabetic patients without renal
      failure and nondiabetic control subjects and their association with coronary
      artery calcification.
AB  - This study examined the role of cholesteryl ester transfer (CET), cholesteryl
      ester transfer protein (CETP) activity, and phospholipid transfer protein (PLTP)
      activity in the increased prevalence of coronary artery calcification (CAC) in
      diabetic subjects compared with nondiabetic subjects and in the loss of the sex
      difference in CAC in diabetes. CETP activity, PLTP activity, and CET were
      measured in 195 type 1 diabetic subjects without renal failure and 194
      nondiabetic control subjects of similar age (30-55 years) and sex distribution
      (50% female). CAC was quantified with electron beam computed tomography. CETP
      activity was higher in diabetic subjects (mean 84 arbitrary units [AU]) than in
      nondiabetic subjects (80 AU, P = 0.028). PLTP activity was also higher in
      diabetic subjects (96 AU) than in nondiabetic subjects (81 AU, P < 0.001).
      However, CET was lower in diabetic men (geometric mean 32 nmol. ml(-1).h(-1))
      than nondiabetic men (37 nmol.ml(-1).h(-1), P = 0.004) and did not differ between
      diabetic (30 nmol. ml(-1).h(-1)) and nondiabetic (32 nmol.ml(-1).h(-1), P = 0.3)
      women. CETP and PLTP activities were not associated with CAC. CET was positively
      associated with CAC in both diabetic and nondiabetic subjects (odds ratio per 10
      nmol.ml(-1).h(-1) increase in CET in all subjects = 1.4, P = 0.001). The
      prevalence of CAC was similar in diabetic (51%) and nondiabetic (54%, P = 0.7)
      men but was much higher in diabetic (47%) than nondiabetic (21%, odds ratio 3.6,
      P < 0.001) women so that there was no sex difference in CAC in diabetic subjects.
      The odds of CAC in diabetic women compared with nondiabetic women was altered
      little by adjustment for CETP activity, PLTP activity, or CET (odds ratio on
      adjustment 3.7, P < 0.001). The greater effect of diabetes on CAC in women than
      in men, i.e., the loss of the sex difference in CAC, was independent of CETP and
      PLTP activity and CET. In conclusion, among both diabetic and nondiabetic
      subjects, higher cholesteryl ester transfer is a risk factor for CAC. However,
      abnormalities in cholesteryl ester transfer or lipid transfer protein activities
      do not underlie the increased CAC risk in diabetic women compared with
      nondiabetic women or the loss of the sex difference in CAC in diabetes.

PMID- 11246888
TI  - Direct regulatory effect of fatty acids on macrophage lipoprotein lipase:
      potential role of PPARs.
AB  - Atherosclerosis is a major complication of type 2 diabetes. The pathogenesis of
      this complication is poorly understood, but it clearly involves production in the
      vascular wall of macrophage (Mo) lipoprotein lipase (LPL). Mo LPL is increased in
      human diabetes. Peripheral factors dysregulated in diabetes, including glucose
      and free fatty acids (FAs), may contribute to this alteration. We previously
      reported that high glucose stimulates LPL production in both J774 murine and
      human Mo. In the present study, we evaluated the direct effect of FAs on murine
      Mo LPL expression and examined the involvement of peroxisome proliferator
      activated receptors (PPARs) in this effect. J774 Mo were cultured for 24 h with
      0.2 mmol/l unsaturated FAs (arachidonic [AA], eicosapentaenoic [EPA], and
      linoleic acids [LA]) and monounsaturated (oleic acid [OA]) and saturated FAs
      (palmitic acid [PA] and stearic acid [SA]) bound to 2% bovine serum albumin. At
      the end of this incubation period, Mo LPL mRNA expression, immunoreactive mass,
      activity, and synthetic rate were measured. Incubation of J774 cells with LA, PA,
      and SA significantly increased Mo LPL mRNA expression. In contrast, exposure of
      these cells to AA and EPA dramatically decreased this parameter. All FAs, with
      the exception of EPA and OA, increased extra- and intracellular LPL
      immunoreactive mass and activity. Intracellular LPL mass and activity paralleled
      extracellular LPL mass and activity in all FA-treated cells. In Mo exposed to AA,
      LA, and PA, an increase in Mo LPL synthetic rate was observed. To evaluate the
      role of PPARs in the modulatory effect of FAs on Mo LPL gene expression, DNA
      binding assays were performed. Results of these experiments demonstrate an
      enhanced binding of nuclear proteins extracted from all FA-treated Mo to the
      peroxisome proliferator-response element (PPRE) consensus sequence of the LPL
      promoter. PA-, SA-, and OA-stimulated binding activity was effectively diminished
      by immunoprecipitation of the nuclear proteins with anti-PPAR-alpha antibodies.
      In contrast, anti-PPAR-gamma antibodies only significantly decreased AA-induced
      binding activity. Overall, these results provide the first evidence for a direct
      regulatory effect of FAs on Mo LPL and suggest a potential role of PPARs in the
      regulation of Mo LPL gene expression by FAs.

PMID- 11246889
TI  - Inhibition of lipid peroxidation restores impaired vascular endothelial growth
      factor expression and stimulates wound healing and angiogenesis in the
      genetically diabetic mouse.
AB  - Impaired wound healing is a well-documented phenomenon in experimental and
      clinical diabetes. Experimental evidence suggests that a defect in vascular
      endothelial growth factor (VEGF) regulation might be associated with wound
      healing disorders. We studied the involvement of lipid peroxidation in the
      pathogenesis of altered VEGF expression in diabetes-related healing deficit by
      using an incisional skin-wound model produced on the back of female diabetic
      C57BL/KsJ db+/ db+ mice and their normal (db+/+m) littermates. Animals were then
      randomized to the following treatment: raxofelast (15 mg.kg(-1).day(-1) i.p.), an
      inhibitor of lipid peroxidation, or its vehicle (DMSO/NaCl 0.9%, 1:1 vol: vol).
      The animals were killed on different days (3, 6, and 12 days after skin injury),
      and the wounded skin tissues were used for histological evaluation, for analysis
      of conjugated dienes (CDs), as an index of lipid peroxidation and wound breaking
      strength. Furthermore, we studied the time course of VEGF mRNA expression
      throughout the skin-repair process (3, 6, and 12 days after skin injury), by
      means of reverse transcriptase-polymerase chain reaction, as well as the mature
      protein in the wounds. Diabetic mice showed impaired wound healing with delayed
      angiogenesis, low breaking strength, and increased wound CD content when compared
      with their normal littermates. In healthy control mice, a strong induction of
      VEGF mRNA was found between day 3 and day 6 after injury, while no significant
      VEGF mRNA expression was observed at day 12 after injury. In contrast, VEGF mRNA
      levels, after an initial increase (day 3), were significantly lower in diabetic
      mice than in normal littermates, and light induction of VEGF mRNA expression was
      also present at day 12 after injury. Similarly, the wound content of the
      angiogenic factor was markedly changed in diabetic mice. Administration of
      raxofelast did not modify the process of wound repair in normal mice, but
      significantly improved the impaired wound healing in diabetic mice through the
      stimulation of angiogenesis, re-epithelization, and synthesis and maturation of
      extracellular matrix. Moreover, raxofelast treatment significantly reduced wound
      CD levels and increased the breaking strength of the wound. Lastly, the
      inhibition of lipid peroxidation restored the defect in VEGF expression during
      the process of skin repair in diabetic mice and normalized the VEGF wound
      content. The current study provides evidence that lipid peroxidation inhibition
      restores wound healing to nearly normal levels in experimental diabetes-impaired
      wounds and normalizes the defect in VEGF regulation associated with diabetes
      induced skin-repair disorders.

PMID- 11246890
TI  - A gene conferring susceptibility to type 2 diabetes in conjunction with obesity
      is located on chromosome 18p11.
AB  - Genome-wide nonparametric linkage analysis of 480 sib-pairs affected with type 2
      diabetes revealed linkage to a previously unreported susceptibility locus on
      chromosome 18p11. This result improved with stringent subphenotyping using age-
      and sex-adjusted BMI, ultimately reaching a logarithm of odds of 3.82 (allele
      sharing 0.6654) at a point between markers D18S976 and D18S391 when the most
      obese 20% of the sample was analyzed. Several genes on chromosome 18 have been
      suggested as metabolic disease candidates, but none of these colocalize with our
      linkage result. We conclude that our results provide support for the presence of
      a currently uncharacterized gene on chromosome 18p, certain alleles of which
      confer increased susceptibility to type 2 diabetes in conjunction with obesity.
      We additionally observed moderate evidence for linkage to chromosome 1, near
      marker D1S3462; chromosome 4, near marker D4S2361; chromosome 5, near marker
      D5S1505; and chromosome 17, near marker D17S1301.

PMID- 11246891
TI  - A genome scan for type 2 diabetes susceptibility loci in a genetically isolated
      population.
AB  - A total of 896 individuals of Ashkenazi Jewish descent were ascertained in Israel
      from 267 multiplex families, including 472 sib-pairs affected with type 2
      diabetes. A genome-wide scan with average marker spacing of 9.5 cM revealed five
      regions on four chromosomes (4q, 8q, 14q, and 20q) that exhibited nominal
      evidence for linkage (P < 0.05). The highest observed nonparametric linkage Z
      score was 2.41 (equivalent to a logarithm of odds score of 1.26) at marker
      D4S1501. A maximal signal, with a Z score of 2.05, was observed on chromosome 20
      near marker D20S195, and another on 20p near marker D20S103 (Z 1.80). A single
      marker on chromosome 8 (D8S593) and two adjacent markers on chromosome 14
      (D14S749 and D14S605) also attained evidence of linkage. To explore the
      hypothesis that the signals on chromosomes 4 and 20 are differentially
      attributable to variation in BMI or age of onset, an ordered subset analysis was
      conducted. This analysis revealed that only when the families were ranked by BMI
      (in increasing order) did a subset attain nominal significance, and only for
      chromosome 4. The findings reported here lend credence to the hypothesis, now
      supported by four studies of Caucasian populations and most recently by a
      combined analysis of 1,852 pedigrees, that a type 2 diabetes susceptibility locus
      resides on chromosome 20q. This population, because of its unique genetic
      attributes, may facilitate identification of this and other genes contributing to
      type 2 diabetes.

PMID- 11246892
TI  - Evidence for gene-nutrient interaction at the PPARgamma locus.
AB  - The importance of the nuclear receptor peroxisome proliferator-activated receptor
      gamma (PPARgamma) in regulating insulin resistance and blood pressure has been
      demonstrated in families with loss of function mutations. Gain of function
      mutations has been associated with severe obesity. However, previous population
      studies of the common variant Pro12Ala have produced conflicting results. As it
      is likely that the natural ligands for this receptor may include fatty acids, we
      hypothesized that the effect of this common variant may be altered by the
      character of the diet, particularly the ratio of dietary polyunsaturated fat to
      saturated fat (P:S ratio). We studied 592 nondiabetic participants in an ongoing
      population-based cohort study who were genotyped for the Pro12Ala polymorphism in
      the PPAR gamma2 isoform. As the Ala homozygotes were uncommon (2.0%), all
      analyses were conducted comparing Pro homozygotes (79.1%) to Ala allele carriers.
      There was no difference in fasting insulin concentration or BMI between Ala
      allele carriers and Pro homozygotes. The fasting insulin concentration was
      negatively associated with the P:S ratio (P = 0.0119) after adjustment for age
      and sex, and a strong interaction was evident between the P:S ratio and the
      Pro12Ala polymorphism for both BMI (P = 0.0038) and fasting insulin (P = 0.0097).
      The data suggest that when the dietary P:S ratio is low, the BMI in Ala carriers
      is greater than that in Pro homozygotes, but when the dietary ratio is high, the
      opposite is seen. This gene-nutrient interaction emphasizes the difficulty of
      examining the effect of common polymorphisms in the absence of data on nongenetic
      exposures, and may explain the heterogeneity of findings in previous studies.

PMID- 11246894
TI  - Mutations in the coding region of the neurogenin 3 gene (NEUROG3) are not a
      common cause of maturity-onset diabetes of the young in Japanese subjects.
AB  - Mutations in transcription factors that play a role in the development of the
      endocrine pancreas, such as insulin promoter factor-1 and NeuroD1/BETA2, have
      been associated with diabetes. Cell type-specific members of the basic helix-loop
      helix (bHLH) family of transcription factors play essential roles in the
      development and maintenance of many differentiated cell types, including
      pancreatic beta-cells. Neurogenin 3 is a bHLH transcription factor that is
      expressed in the developing central nervous system and the embryonic pancreas.
      Mice lacking this transcription factor fail to develop any islet endocrine cells
      and die postnatally from diabetes. Because neurogenin 3 is required for the
      development of beta-cells and other pancreatic islet cell types, we considered it
      a candidate diabetes gene. We screened the coding region of the human neurogenin
      3 gene (NEUROG3) for mutations in a group of unrelated Japanese subjects with
      maturity-onset diabetes of the young (MODY). We found three sequence variants: a
      deletion of 2-bp in the 5'-untranslated region (NEUROG3-g.-44-45delCA), a G-to-A
      substitution in codon 167 (g.499G/ A), resulting in a Gly-to-Arg replacement
      (G/R167), and a T-to-C substitution in codon 199 (g.596T/C), resulting in a
      Phe/Ser polymorphism F/S199. These polymorphisms were not associated with MODY,
      thereby suggesting that mutations in NEUROG3 are not a common cause of MODY in
      Japanese patients.

PMID- 11246893
TI  - In vitro and in vivo studies of a naturally occurring variant of the human
      p85alpha regulatory subunit of the phosphoinositide 3-kinase: inhibition of
      protein kinase B and relationships with type 2 diabetes, insulin secretion,
      glucose disappearance constant, and insulin sensitivity.
AB  - In humans, the Met326Ile missense variant of the p85alpha regulatory subunit of
      the phosphoinositide 3-kinase (PI3K) has been associated with either significant
      reductions in glucose effectiveness and intravenous glucose tolerance in
      Caucasians or a significantly higher insulin secretory response in Pima Indians.
      In the present study, we genotyped 1,190 Caucasian males to evaluate the impact
      in vivo of the Met326Ile variant of the p85alpha subunit of PI3K on the acute
      insulin response, intravenous glucose tolerance, insulin-mediated glucose uptake,
      and the prevalence of type 2 diabetes after 20 years of follow-up. We also
      expressed the variant in vitro to evaluate the impact on insulin-stimulated
      activation of protein kinase B (PKB). The Met326Ile variant of p85alpha was not
      associated with type 2 diabetes or with alterations in insulin secretion, insulin
      sensitivity, or intravenous glucose tolerance in vivo. Expressed in vitro, the
      Ile326 and the Met326 variant acted equally as a dominant-negative and prevented
      (60-70% inhibition) insulin-mediated activation of PKB by inhibiting the
      phosphorylation of PKB at Thr308. We conclude that the Met326Ile variant of the
      p85alpha regulatory subunit of PI3K is likely to be as functionally normal in
      vivo as in vitro.

PMID- 11246896
TI  - Cumulative author and subject index for volumes 35-72.

PMID- 11246895
TI  - Decreased fasting and oral glucose stimulated C-peptide in nondiabetic subjects
      with sequence variants in the sulfonylurea receptor 1 gene.
AB  - The high-affinity sulfonylurea receptor 1 (SUR1) plays an important role in
      regulating insulin secretion. In the Quebec Family Study, we genotyped 731
      individuals (685 nondiabetic [ND] subjects) for the SUR1 gene IVS15-3c-->t and
      exon 18 Thr759(ACC-->ACT) polymorphisms using polymerase chain reaction
      restriction fragment-length polymorphism analysis. Phenotypes measured were
      fasting plasma glucose (GLU), fasting plasma insulin (INS), and fasting C-peptide
      (CPEP), as well as oral glucose tolerance test (OGTT) responses; they were
      adjusted for age, sex, waist circumference, and the sum of six skinfold
      thicknesses. In ND subjects, exon 18 Thr759(ACC-->ACT) T allele carriers (T+) had
      lower CPEP (P = 0.022, -12.8%) and acute C-peptide responses (area above basal in
      first 30 min [CP30]) (P = 0.051, -12.4%) than noncarriers (T-). Also, in those
      with the cT/tC haplotype (from both IVS15-3c-->t and exon 18 Thr759[ACC-->ACT]
      polymorphisms), CPEP (P = 0.005, -21.2%), CP30 (P = 0.034, -19.2%), and total C
      peptide responses (P = 0.016, -20.2%) were lower than that in cT- subjects. In
      overweight individuals (BMI >25 kg/m2), differences between carriers and
      noncarriers of the T or cT alleles were greater for GLU (P = 0.023-0.034), CPEP
      (P = 0.021-0.015), acute OGTT insulin response (P = 0.014-0.019), and CP30 (P =
      0.034-0.019). These results suggest that the T and cT allele variants are
      associated with lower insulin secretion parameters, particularly in female and
      overweight subjects, adding evidence to the role of SUR1 sequence variants in
      decreased insulin secretion.

PMID- 11246897
TI  - Solving the surgical waiting list problem? New Zealand's 'booking system'.
AB  - This article discusses the development and implementation of New Zealand's
      booking system for publicly funded non-urgent surgical and medical procedures.
      The 'booking system' emerged out of New Zealand's core services debate and the
      government's desire to remove waiting lists. It was targeted for implementation
      by mid-1998. However, the booking system remains in an unsatisfactory state and a
      variety of problems have plagued its introduction. These include a lack of
      national consistency in the priority access criteria, failure to pilot the system
      and a shortfall in the levels of funding available to treat the numbers of
      patients whose priority criteria 'scores' deem them clinically eligible for
      surgery. The article discusses endeavours to address these problems. In
      conclusion, based on the New Zealand experience, the article provides lessons for
      policy-makers interested in introducing surgical booking systems.

PMID- 11246898
TI  - Vertical or holistic decentralization of the health sector? Experiences from
      Zambia and Uganda.
AB  - Many countries in Africa have embarked on health sector reforms. The design of
      the reforms differs considerably. A key feature of the reforms is
      decentralization, of which Uganda and Zambia are implementing two different
      models. This paper analyses the two models of health sector reform, and their
      implications for ultimate development goals. In Uganda, the whole government has
      been decentralized, with a wide range of powers and resources transferred to the
      districts. The health care system is part of the political set up of the country.
      In Zambia, only the health sector has been decentralized. Power and resources for
      health care have been divested to new parallel organizations. While useful
      lessons can be drawn from the managerial and administrative experience in the two
      countries, not least concerning donor coordination, it seems that neither form of
      decentralization has so far led to a clear and appreciable improvement of health
      services and, ultimately, to a clear focus on development goals, such as poverty
      alleviation. The conditions for this to happen are discussed in this paper.

PMID- 11246899
TI  - The equity impacts of community financing activities in three African countries.
AB  - Although the Bamako Initiative from its very beginning was caught up in wider
      debates about the potential equity impact of any form of user financing, to date
      there has been little empirical investigation of this impact. This three-country
      study, undertaken in Benin, Kenya and Zambia in 1994/95, was initiated to add to
      the body of relevant evidence. It sought to understand not only what had been the
      equity impacts of community financing activities in these countries but also how
      they had been brought about. As a result, it investigated equity primarily
      through consideration of the design of these financing activities and through the
      perceptions of different actors, within a limited number of purposively selected
      geographical areas in each country, about their strengths and weaknesses.
      Additional data on utilization were either collected during the course of the
      study (Kenya) or drawn from other available studies (Benin and Zambia). Key
      issues considered in the studies' assessment of equity were the extent to which
      both relative and absolute affordability gains were achieved, as well as as an
      influence over both the distributional and procedural justice of the financing
      activities, the pattern of decision-making. Across countries there was evidence
      of relative affordability gains in Benin and Kenya, but Kenyan gains were not
      sustained over time and no such gains were identified in Zambia. In addition, no
      country had given attention either to the issue of absolute affordability,
      through the implementation of effective exemption mechanisms to protect the
      poorest from the burden of payment, or to the establishment of community decision
      making bodies that effectively represented the interests of all groups including
      the poorest. Overall, therefore, although the Benin Bamako Initiative programme
      might be judged as successful in terms of what appear to be its own equity
      objectives, the other two countries' schemes had clear equity problems even in
      these terms. The experience across countries also highlights the unresolved
      question of whether equity is concerned with the greatest good for the greatest
      number or with promoting the interests of the most disadvantaged.

PMID- 11246901
TI  - Health sector reform and STD/AIDS control in resource poor settings--the case of
      Tanzania.
AB  - Integration in health sector reform tends to mean horizontal interaction between
      vertical programmes. This can result in a larger more complex system than a set
      of individual vertical programmes. This article looks at the HIV/AIDS programme
      in Tanzania and the possible impact of system-wide health sector reform involving
      'decentralization' and horizontal integration. It implies that the build-up to
      reform is likely to be costly, at least initially (although eventually the system
      may become more cost-effective). Integration can thus save resources, but it will
      also demand additional inputs, and may lead to reduced service output if
      operations depend on horizontal functions that fail to deliver. The objective of
      reform must be to create a reasonably sized, well-balanced, system which aims to
      maximize the output of quality services, both preventive and curative, and to
      facilitate community efforts to improve health. It is doubtful whether present
      reform efforts in Tanzania will contribute to more effective services, if not
      based on a more thorough analysis adapted to the local situation and given
      considerably more resources, both human and financial. There is also a risk that
      key preventive programmes, such as those aimed at the control of STD/AIDS, will
      be further weakened because of both integration with subsequent dependence on
      poorly functioning horizontal units and reduction in allocated resources.

PMID- 11246900
TI  - Financing health care at the local level: the community drug funds of Honduras.
AB  - In response to UNICEF's Bamako Initiative, hundreds of privately run Community
      Drug Funds were established in Honduras during the 1990s, generally under the
      auspices of a non-government organization and usually with the financial
      assistance of international agencies. Honduras' Community Drug Funds (CDF) are
      rotating drug funds intended to: (1) serve as a means of increasing access to
      care in isolated rural populations, (2) promote the more rational use of
      medicines and (3) promote community participation in the financing and oversight
      of primary health care activities. This study is the first to analyse empirically
      the impact and efficiency of these institutions, relying upon primary data
      obtained from a survey of 51 of the 450 active CDFs in Honduras. Archival data
      from Ministry of Health and other sources were also analysed. The structure,
      operations, and impact of CDFs are detailed, with special attention given to
      access and quality of care issues. The study found that CDFs are rapidly becoming
      under-capitalized because of basic management problems, principally in pricing
      and in medicine purchasing practices. These shortcomings, and more generally,
      increasing financial pressures on NGO sponsors, are negatively affecting quality
      and access to care. Given the rate of erosion in CDF assets, unless they are
      recapitalized, the current average estimated lifespan of a CDF is 5.5 years. If
      these funds are to be sustainable, changes in their financing, training and
      supervision will be required. In addressing these issues, Honduran health policy
      makers must decide how best to balance the competing goals of holding down costs,
      while maintaining adequate quality and improving access to care.

PMID- 11246902
TI  - The microbiology of South African traditional fermented milks.
AB  - A total of 15 samples of traditional fermented milk were collected from
      individual households in South Africa and Namibia. Lactic acid bacteria dominated
      the microflora of these samples, especially the genera Leuconostoc, Lactococcus
      and Lactobacillus. Other groups identified included pyogenic streptococci and
      enterococci. The dominant lactococci species was Lactococcus lactis subsp.
      lactis. Eighty-three percent of the leuconostoc isolates were identified as
      Leuconostoc mesenteroides subsp. dextranicum. Other species identified included
      Leuconostoc citreum, Leuconostoc lactis, Lactobacillus delbrueckii subsp. lactis
      and Lactobacillus plantarum.

PMID- 11246903
TI  - Prevalence and behaviour of Bacillus cereus in a REPFED of Italian origin.
AB  - This paper reports on the prevalence and behaviour of Bacillus cereus in gnocchi,
      a REPFED of Italian origin. A survey of gnocchi under varying storage conditions,
      revealed that, although B. cereus was found in 33% of the samples, the
      contamination level was lower than 10(2) CFU/g for the unstored and the
      refrigerated (8 degrees C) samples. Counts increased with increasing storage
      temperatures and prolonged storage times in samples prepared without sorbic acid.
      The effect of different formulations (sorbic, citric and lactic acid) and storage
      conditions (8, 12 and 20 degrees C) have been evaluated in a challenge testing
      with spores of B. cereus. Results indicate that the use of sorbic acid in
      association with citric or lactic acid to pH 5.0 is effective in inhibiting
      growth of B. cereus and the anticipated shelf life of the product is safe even if
      temperature abuse occurs. If sorbic acid is omitted, lactic acid can inhibit B.
      cereus growth during storage at 8 degrees C. On the contrary, when temperature
      abuse occurs (12 and 20 degrees C), lactic or citric acid are not able to prevent
      growth of B. cereus.

PMID- 11246904
TI  - Effect of sodium chloride concentration on the heat resistance and recovery of
      Salmonella typhimurium.
AB  - The survival of Salmonella typhimurium (ATCC 13311) heated and recovered in media
      with 0, 1, 2, 3, 4 or 5% (w/w) added sodium chloride was investigated. A
      protective effect in the heating medium and an inhibitory effect in the recovery
      medium were observed. The results showed an interaction between the effect on,
      D(58 degrees C) values, of sodium chloride concentration in both media. Lower
      concentration in the heating media led to a greater effect of the sodium chloride
      concentration in the recovery media. When the sodium chloride concentration was
      the same in both media, the protective effect exerted in the heating media
      dominated over its inhibitory effect in the recovery media.

PMID- 11246905
TI  - Characterization of Shiga toxin producing E. coli and O157 serotype E. coli
      isolated in France from healthy domestic cattle.
AB  - A study was carried out in France in collaboration with the meat industry to
      investigate the occurrence and characteristics of Shiga toxin-producing E. coli
      (STEC) and O157 E. coli in a population of healthy bovines representative of
      French livestock. A total of 851 animals belonging to three bovine classes (106
      young bulls, 374 dairy cows and 371 meat cows) were included in the study.
      Samples of feces and of the corresponding carcasses were collected from March 97
      to August 97 in seven abattoirs spread throughout the national territory. STEC
      cultures from the 1702 samples were screened using PCR for the presence of stx
      genes. Positive samples were further subjected to colony blot hybridization and
      to O157-specific immunomagnetic separation. Probe-positive colonies and O157
      colonies were then analyzed for the presence of virulence genes and phenotypic
      characters (serotype, Stx production). In 154 (18.1%) feces and 91 (10.7%)
      carcass samples stx genes were detected. Two hundred and twenty-two STEC colonies
      were isolated from 67 (7.9%) feces and 16 (1.9%) carcass samples, with 183 STEC
      isolated from feces and 39 from carcasses. Only eight O157 isolates were
      collected from feces samples. None of these O157 E. coli isolates presented stx
      genes and thus could not be considered as pathogenic regarding hemorrhagic
      colitis (HC) and hemolytic uremic syndrome (HUS). In 3.2% of STEC isolated from
      feces and in 10.2% of STEC from carcasses eae genes were detected. In 17% of STEC
      from feces and in 30.7% from carcasses ehx genes were detected. Using these data,
      the 222 STEC colonies could be classified in 11 different 'virulence patterns'
      (presence/absence of stx1, stx2, eae and ehx genes), showing that more than 77%
      of isolates presented only one virulence factor. Only three STEC on 222 colonies
      (1.3%) presented the three virulence factors stx, eae and ehx in association,
      none of them reacting with antisera specific for enterohemorrhagic E. coli.
      (EHEC). These data, together with the fact that only five isolates on the 222
      (2.2%) reacted with such antisera (three O111 and two O26 isolates) demonstrated
      that the natural bacterial populations isolated during this study were clearly
      distinct from EHEC.

PMID- 11246906
TI  - Automated simultaneous detection of low levels of listeriae and salmonellae in
      foods.
AB  - Salmonella spp. and Listeria monocytogenes continue to be major pathogens of
      concern to food processors. However, routine screening of food samples to detect
      these pathogens is generally labor intensive and costly. Automated optical
      procedures for the detection of salmonellae and listeriae in foods were developed
      in our laboratory. In the present study we report their adaptation to a
      simultaneous recovery and detection procedure. Milk, shell eggs, fresh and ready
      to-eat (RTE) meats or raw chicken contaminated with a combination of sub-lethally
      injured salmonellae and listeriae (10-50 cells each) were incubated for 6 h at 35
      degrees C in modified universal pre-enrichment broth (MUPB). Volumes (4 ml) were
      then transferred to vials containing selective liquid media for these pathogens
      (4 ml), and incubated overnight at 35 degrees C in a BioSys instrument. The
      presence of the pathogens was identified by a black coloration of the media and a
      sharp drop in light transmittance caused by hydrogen sulfide production
      (Salmonella organisms), or esculin hydrolysis (Listeria organisms). There was no
      difference in the detection time of salmonellae when incubated alone or with
      listeriae, but listeriae grew at a slower rate in the presence of salmonellae,
      resulting in a delay of < or = 1 h in their detection. Overall, the detection of
      10-50 salmonellae and 10-50 listeriae in 25 g of the tested foods required a
      total of 24 h. Confirmation of the pathogens by PCR-based assay (6 h) was
      completed the following day directly from positive vials, requiring a total of <
      or = 30 h for detection and confirmation. Negative samples required no
      confirmation. The testing system was confirmed in 70 naturally contaminated
      foods.

PMID- 11246907
TI  - Effect of different complex carbon sources on growth and bacteriocin synthesis of
      Enterococcus faecium.
AB  - Different criteria are followed in order to select bacteria to be used in
      probiotic and symbiotic supplements. A new parameter to choose strains could be
      fermentation by intestinal bacteria of some complex carbohydrates because they
      are prebiotics and promote the development of beneficial microorganisms in the
      intestinal environment. An Enterococcus faecium strain, isolated from the crop of
      a free-range chicken, was assayed in order to determine the utilization of
      commercial sugars and/or crude carbohydrate samples from a sugar mill. The
      production of antimicrobial substances, under these conditions, was also
      considered. Ent. faecium CRL1385 grew well in the presence of complex
      carbohydrates and its ability to produce bacteriocin, active against poultry
      pathogens such as Ent. hirae, Salmonella pullorum and Listeria monocytogenes, was
      not significantly modified. These results are promising because the trend today
      is to employ eubiotic or symbiotic products and their use in the poultry industry
      could be a natural way to protect the flocks against potential pathogens.

PMID- 11246908
TI  - Effects of hot water pasteurizing treatments on the microbiological condition of
      manufacturing beef used for hamburger patty manufacture.
AB  - Ten 12-kg lots of manufacturing beef from a single packing plant were obtained
      from a hamburger patty manufacturing plant. Each lot was divided into two, 6-kg
      portions, one of which was not treated while the other was treated with water of
      85 degrees C. A portion from one lot was treated for 15 s. A portion from each of
      three lots was treated for 30 s, three portions were treated for 45 s, and three
      were treated for 60 s. Twenty-five pieces of meat from each portion were swabbed
      over areas of 100 cm2. Subsequently, each portion was first coarsely ground then
      finely ground, with twenty-five 100-g samples being taken from each portion at
      each stage of grinding. Each swab and sample of ground meat was separately
      processed for the enumeration of total aerobic counts, coliforms and Escherichia
      coli at levels of detection of 1 cfu/cm2, 1 cfu/100 cm2 and 1 cfu/100 cm2,
      respectively, for swab samples; and at a level of detection of 1 cfu/g for all
      three types of bacteria in samples of ground beef. A 250-kg batch of
      manufacturing beef was treated with water of 85 degrees C for 60 s. The product
      was processed through commercial equipment for manufacturing frozen hamburger
      patties. The flavour of patties prepared from the pasteurized product was
      compared with the flavour of patties prepared during normal commercial operation
      of the equipment. The weight of the manufacturing beef was not affected by the
      treatments. Similar total numbers of coliforms or E. coli were recovered per 2500
      cm2 from the 25 swab samples or per 25 g from the 25 ground beef samples from
      each untreated portion. As the ratio of the surface area in cm2 to the weight in
      g would likely be < or = 1, the similar numbers indicated that swab sampling was
      inefficient for recovering coliforms and E. coli from the meat. However,
      coliforms and E. coli were recovered more frequently from swab than from ground
      beef samples from treated portions. Thus, some swabs from all three portions of
      beef treated for 30 s yielded coliforms and E. coli, but samples from portions
      treated for 45 or 60 s yielded few coliforms and no E. coli. The numbers
      recovered from the treated and untreated portions indicated that treatments for
      45 or 60 s reduced both coliform and E. coli numbers by two orders of magnitude.
      The flavours of cooked patties prepared from the meat pasteurized with water of
      85 degrees C for 60 s were not distinguished from the normal commercial product.
      The data indicate that pasteurizing manufacturing beef with water of 85 degrees C
      for 45 s could be a practicable treatment for enhancing the microbiological
      safety of frozen hamburger patties.

PMID- 11246909
TI  - Effect of heat activation and inactivation conditions on germination and thermal
      resistance parameters of Bacillus cereus spores.
AB  - The effect of isothermal and non-isothermal heat activation on germination and
      thermoresistance of two strains of Bacillus cereus spores was studied. Results
      indicated that the germination after isothermal activation was lower than after
      non-isothermal heating. The activation rate affected the z value, which increased
      with faster heating rates. For each temperature and inactivation rate, the non
      isothermal activation at rate of 2 degrees C/min resulted in larger D values (D90
      = 4.70 min) than isothermal activation (D90 = 4.04 min). The two mathematical
      equations used to analyse non-isothermal data produced similar predicted D and z
      values, nevertheless the Hayakawa equation modified in this work for non-linear
      regression analysis, requires less computational effort.

PMID- 11246910
TI  - A cardinal model to describe the effect of water activity on the growth of
      moulds.
AB  - A simple model was proposed to describe the effect of water activity (Aw) on the
      radial growth rate of moulds. This model is deduced from the cardinal model
      family proposed by Rosso in 1995, which is only defined from cardinal values of
      environmental factors (minimum, optimum and maximum values), the growth rate
      observed at the optimal value of the environmental factors, and n, a shape
      parameter. For Aw, a simple form of cardinal model is proposed. This form is
      obtained for n = 2 and Aw(max) = 1.0 (pure water). The final model is so defined
      from only three parameters: Aw(min), Aw(opt), and optimal radial growth rate
      (RGR(opt)). This model was successfully fitted on a data set of Aspergillus
      flavus, Aspergillus nomius, Aspergillus oryzae, Aspergillus parasiticus,
      Aspergillus candidus, Aspergillus sydowii, Eurotium amstelodami, Eurotium
      chevalieri, and Xeromyces bisporus. The same quality of fit was obtained for
      different solutes used to control the Aw (NaCl, glucose/fructose mixture,
      glycerol), and at different pH values. From this model and using cardinal values
      extracted from the literature, theoretical evolutions of the RGR of enicillium
      roqueforti, and Paecilomyces variotii, were proposed and superimposed on data
      published in the literature. The results showed a good concordance between the
      predicted and the observed values for these species. The use of this model in
      Predictive Microbiology is discussed.

PMID- 11246911
TI  - Characterization and evaluation of some virulence markers of Listeria
      monocytogenes strains isolated from Brazilian cheeses using molecular,
      biochemical and serotyping techniques.
AB  - A total of 207 L. monocytogenes strains isolated from different types of cheeses
      commercialized in the city of Rio de Janeiro, Brazil, were serotyped and
      evaluated for their ability to produce beta-haemolysin and lecithinase and to
      adsorb Congo red dye. Of the 207 strains, 59.9, 27.5 and 12.6% belonged to
      serotypes 1/2a, 1/2b and 4b, respectively. In addition, 175 strains of L.
      monocytogenes produced lecithinase while strains of the other species did not.
      Some of the non-L. monocytogenes strains adsorbed the dye Congo red, while some
      L. monocytogenes did not. Statistical analysis of the results showed significant
      differences (P < 0.05) amongst the virulence tests and the three serotypes found.
      In the present study, 32 L. monocytogenes strains were also analyzed by RAPD
      (randomly amplified polymorphic DNA). RAPD analysis allowed the discrimination
      among strains of different serotypes, as well as among strains of the same
      serotype. It is important to emphasize that the use of more than one primer is
      needed for characterization of L. monocytogenes strains. With RAPD the strains
      were grouped into six different profiles, some of them common for strains
      belonging to different serotypes. The results also indicated a close genetic
      relationship among strains of different serotypes.

PMID- 11246912
TI  - Survival of Helicobacter pylori in ready-to-eat foods at 4 degrees C.
AB  - The survival of Helicobacter pylori (NCTC 11638) in various semiprocessed and
      fresh, ready-to-eat foods, and one raw chicken was studied at 4 degrees C and
      under aerobic conditions by experimentally inoculating these with 10(4) CFU.
      Cells were concentrated by two centrifugation cycles followed by plating onto
      selective blood agar medium made from Wilkins-Chalgren agar supplemented with 5%
      whole horse blood, and 30 mg/l colistin methanesulfonate, 100 mg/l cycloheximide,
      30 mg/l nalidixic acid, 30 mg/l trimethoprim, and 10 mg/l vancomycin. H. pylori
      was recovered from spiked pasteurized milk and tofu samples up to 5 days and from
      spiked leaf lettuce and raw chicken up to 2 days. H. pylori could not be
      recovered from yogurt after any length of storage time. H. pylori is unlikely to
      grow in foods; however, it may survive in low acid-high moisture environments
      under refrigeration and pose a possible risk for transmission of infection via
      foods.

PMID- 11246913
TI  - Bibliography of food microbiology.

PMID- 11246914
TI  - California cap rates up, but will other states follow?

PMID- 11246915
TI  - Cardiac cath utilization and costs rising quickly.

PMID- 11246916
TI  - Study documents impact of mental disorders on overall health care utilization,
      claims.

PMID- 11246917
TI  - New data source offers snapshot of population health.

PMID- 11246918
TI  - Introducing T-shaped managers. Knowledge management's next generation.
AB  - Most companies do a poor job of capitalizing on the wealth of expertise scattered
      across their organizations. That's because they tend to rely on centralized
      knowledge-management systems and technologies. But such systems are really only
      good at distributing explicit knowledge, the kind that can be captured and
      codified for general use. They're not very good at transferring implicit
      knowledge, the kind needed to generate new insights and creative ways of tackling
      business problems or opportunities. The authors suggest another approach,
      something they call T-shaped management, which requires executives to share
      knowledge freely across their organization (the horizontal part of the "T"),
      while remaining fiercely committed to their individual business unit's
      performance (the vertical part). A few companies are starting to use this
      approach, and one--BP Amoco--has been especially successful. From BP's
      experience, the authors have gleaned five ways that T-shaped managers help
      companies capitalize on their inherent knowledge. They increase efficiency by
      transferring best practices. They improve the quality of decision making
      companywide. They grow revenues through shared expertise. They develop new
      business opportunities through the cross-pollination of ideas. And they make bold
      strategic moves possible by delivering well-coordinated implementation. All that
      takes time, and BP's managers have had to learn how to balance that time against
      the attention they must pay to their own units. The authors suggest, however,
      that it's worth the effort to find such a balance to more fully realize the
      immense value of the knowledge lying idle within so many companies.

PMID- 11246919
TI  - High tech the old-fashioned way. An interview with Tom Siebel of Siebel Systems.
      Interview by Bronwyn Fryer.
AB  - There is a growing awareness among corporations that the quality of the customer
      experience they provide directly affects their bottom line. Many are turning to
      high-flying software maker Siebel Systems for help in managing those
      relationships. The young company holds a leadership position in an explosive
      market-enterprise application software. But customer satisfaction, not dot-com
      chic, is foremost on the mind of Siebel Systems' founder, chairman, and CEO, Tom
      Siebel. The buttoned-down Siebel rejects the freewheeling management style and
      culture that characterize many Silicon Valley companies. As the former CEO of
      Gain Technology and a former executive at Oracle, Siebel believes in putting
      customers ahead of technology, discipline ahead of inspiration. In this
      interview, conducted at the company's San Mateo, California, headquarters, Siebel
      describes how this obsessive focus on customer satisfaction has been the driving
      force behind the company's success. He talks about how the organization remains
      true to its core values: a deep commitment to providing customer satisfaction;
      responsible fiscal practices that have created a cash-positive business amid
      today's cash-negative dot-coms; and general professionalism. "The notion of
      dressing in jeans and a T-shirt to greet the CEO of a major financial institution
      who just got off the plane from Munich is not acceptable," he says. Siebel
      Systems rejects the concept of going to war with rivals; instead, the CEO says,
      the company has forged an ecosystem of partnerships that allows it to support and
      integrate its own systems with other companies' software products and ultimately
      ease the customer's software installations. Indeed, Siebel says, the CEO's most
      important job is to understand what customers need and deliver that.

PMID- 11246920
TI  - Unleash innovation in foreign subsidiaries.
AB  - In multinational corporations, growth-triggering innovation often emerges in
      foreign subsidiaries from employees closest to customers and least attached to
      the procedures and politeness of the home office. But too often, heavy-handed
      responses from headquarters squelch local enthusiasm and drive out good ideas-
      and good people. The authors' research into more than 50 multinationals suggests
      that encouraging innovation in foreign subsidiaries requires a change in
      attitude. Companies should start to think of foreign subsidiaries as peninsulas
      rather than as islands--as extensions of the company's strategic domain rather
      than as isolated outposts. If they do, innovative ideas will flow more freely
      from the periphery to the corporate center. Basing their arguments on a rich
      array of examples, the authors say that encouraging such "innovation at the
      edges" also requires a new set of practices, with two aims: to improve the formal
      and informal channels of communication between headquarters and subsidiaries and
      to give foreign subsidiaries more authority to see their ideas through. The
      challenge for executives of multinationals is to find ways to liberalize, not
      tighten, internal systems and to delegate more authority to local subsidiaries.
      It isn't enough to ask subsidiary managers to be innovative; corporate managers
      need to give them incentives and support systems to facilitate their efforts. The
      authors suggest four approaches: give seed money to subsidiaries; use formal
      requests for proposals as a way of increasing the demand for seed money;
      encourage subsidiaries to be incubators for fledgling businesses; and build
      international networks. As part of the last approach, multinationals also need to
      create roles for idea brokers who can link entrepreneurs in foreign subsidiaries
      with other parts of the company.

PMID- 11246922
TI  - Mommy-track backlash.
AB  - "Please don't tell me that I need to have a baby to have this time off." Those
      words were still ringing in the ears of Jessica Gonon an hour after a tense
      meeting with Jana Rowe, one of her key account managers. Jessica, the vice
      president of sales and customer support at ClarityBase, considered Jana's request
      for a four-day workweek, for which she was willing to take a corresponding 20%
      cut in pay. Although the facts seemed simple, the situation was anything but.
      Just last week, Davis Bennett, another account manager, had made a similar
      request. He wanted a lighter workload so he could train for the Ironman Triathlon
      World Championship. Both Jana and Davis were well aware that Megan Flood, another
      account manager, had been working a reduced schedule for nearly two years. When
      she was hired, Megan had requested Fridays off to spend time with her two young
      sons. And since she came highly recommended and the talent pool was tight,
      Jessica had agreed to the arrangement. The eight account managers at ClarityBase
      were in charge of helping the company's largest clients install and maintain
      database applications, which often required no small amount of hand-holding and
      coddling. Because Megan had an abbreviated schedule, the other account managers
      were assigned the more difficult clients. But if Jessica agreed to a shorter
      workweek for Jana and Davis, who would take on the toughest customers? And what
      would happen if the other account managers started asking for similar deals? How
      can Jessica maintain the productivity of her department and meet her staff's
      needs for flexible work schedules while striking an equitable solution for both
      parents and nonparents? Four experts advise Jessica on her next move in this
      fictional case study.

PMID- 11246921
TI  - Making the most of on-line recruiting.
AB  - Ninety percent of large U.S. companies are already recruiting via the Internet.
      By simply logging on to the Web, company recruiters can locate vast numbers of
      qualified candidates for jobs at every level, screen them in minutes, and contact
      the most promising ones immediately. The payoffs can be enormous: it costs
      substantially less to hire someone on-line, and the time saved is equally great.
      In this article, Peter Cappelli examines some of the emerging service providers
      and technologies--matchmakers, job boards, hiring management systems software,
      and applicant-screening mechanisms that test skills and record interests. He also
      looks at some of the strategies companies are adopting as they enter on-line
      labor markets. Recruiting needs to be refashioned to resemble marketing, he
      stresses. Accordingly, smart companies are designing Web pages, and even product
      ads, with potential recruits in mind. They're giving line managers authority to
      hire so that candidates in cyberspace aren't lost. They're building internal on
      line job networks to retain talent. Integrating recruiting efforts with overall
      marketing campaigns, especially through coordination and identification with the
      company's brand, is the most important thing companies can do to ensure success
      in on-line hiring. Along the way, Cappelli sounds two cautionary notes. First, a
      human touch, not electronic contact, is vital in the last steps of a successful
      hiring process. Second, companies must make sure that on-line testing and hiring
      criteria do not discriminate against women, disabled people, workers over 40, or
      members of minority groups. When competition for talent is fierce, companies that
      master the art and science of on-line recruiting will be the ones that attract
      and keep the best people.

PMID- 11246923
TI  - The job no CEO should delegate.
AB  - In 1991, AlliedSignal was in poor shape: morale was low, operating margins were
      lower than 5%, return on equity was only 10.5%, and--most troubling--the
      operating management team was weak. But by 1999, when AlliedSignal merged with
      Honeywell, it was a strong and thriving business. Operating margins had tripled,
      return on equity stood near 28%, and it had a top-notch management group. How did
      the company right its course? Larry Bossidy, CEO of AlliedSignal from 1991
      through 1999, believes the turnaround was made possible by a dramatic improvement
      in people processes. And the extraordinary amount of time and emotional energy he
      put into evaluating, recruiting, and developing great managers-tasks that most
      CEOs delegate--was the key to this process improvement. In this First Person
      article, Bossidy explains why he believes the interview "is the most flawed
      process in American business." He talks candidly about how he assesses candidates
      and what types of questions he asks references. He also describes the four
      leadership traits he looks for when evaluating job candidates: first, the ability
      to execute--that is, being able to turn ideas into reality. The second trait is
      what Bossidy calls "a career runway." When Bossidy hires someone, he wants to
      hire him or her for this job and the next job, never for the person's final
      position. A third quality is a team orientation--good leaders are able to work
      well with others. And the fourth quality is having a wide range of experience. To
      build their skill sets, Bossidy tries to ensure that up-and-coming executives sit
      in many seats en route to leadership roles.

PMID- 11246924
TI  - The Nut Island effect. When good teams go wrong.
AB  - The team that operated the Nut Island sewage treatment plant in Quincy,
      Massachusetts, was every manager's dream. Members of the group performed
      difficult, dangerous work without complaint. They needed little supervision. They
      improvised their way around operational difficulties and budgetary constraints.
      They were dedicated to the organization's mission. But their hard work led to
      catastrophic failure. How could such a good team go so wrong? In this article,
      the author tells the story of the Nut Island plant and identifies a common, yet
      destructive organizational dynamic that can strike any business. The Nut Island
      effect begins with a deeply committed team that is isolated from a company's
      mainstream activities. Pitted against this team is its senior management.
      Preoccupied with high-visibility problems, management assigns the team a vital
      but behind-the-scenes task. Allowed considerable autonomy, team members become
      adept at managing themselves. Management takes the team's self-sufficiency for
      granted and ignores team members when they ask for help. When trouble strikes and
      management is unresponsive, team members feel betrayed and develop an us-against
      the-world mentality. They stay out of management's line of sight, hiding
      problems. The team begins to make up its own rules, which mask grave problems in
      its operations. Management, disinclined in the first place to focus on the team's
      work, is easily misled by team members' skillful disguising of its performance
      deficiencies. The resulting stalemate typically can be broken only by an external
      event. The Nut Island story serves as a warning to managers who concentrate their
      efforts on their organization's most visible shortcomings: sometimes the most
      debilitating problems are the ones we can't see.

PMID- 11246925
TI  - Strategy and the Internet.
AB  - Many of the pioneers of Internet business, both dot-coms and established
      companies, have competed in ways that violate nearly every precept of good
      strategy. Rather than focus on profits, they have chased customers
      indiscriminately through discounting, channel incentives, and advertising. Rather
      than concentrate on delivering value that earns an attractive price from
      customers, they have pursued indirect revenues such as advertising and click
      through fees. Rather than make trade-offs, they have rushed to offer every
      conceivable product or service. It did not have to be this way--and it does not
      have to be in the future. When it comes to reinforcing a distinctive strategy,
      Michael Porter argues, the Internet provides a better technological platform than
      previous generations of IT. Gaining competitive advantage does not require a
      radically new approach to business; it requires building on the proven principles
      of effective strategy. Porter argues that, contrary to recent thought, the
      Internet is not disruptive to most existing industries and established companies.
      It rarely nullifies important sources of competitive advantage in an industry; it
      often makes them even more valuable. And as all companies embrace Internet
      technology, the Internet itself will be neutralized as a source of advantage.
      Robust competitive advantages will arise instead from traditional strengths such
      as unique products, proprietary content, and distinctive physical activities.
      Internet technology may be able to fortify those advantages, but it is unlikely
      to supplant them. Porter debunks such Internet myths as first-mover advantage,
      the power of virtual companies, and the multiplying rewards of network effects.
      He disentangles the distorted signals from the marketplace, explains why the
      Internet complements rather than cannibalizes existing ways of doing business,
      and outlines strategic imperatives for dot-coms and traditional companies.

PMID- 11246926
TI  - Building the emotional intelligence of groups.
AB  - The management world knows by now that to be effective in the workplace, an
      individual needs high emotional intelligence. What isn't so well understood is
      that teams need it, too. Citing such companies as IDEO, Hewlett-Packard, and the
      Hay Group, the authors show that high emotional intelligence is at the heart of
      effective teams. These teams behave in ways that build relationships both inside
      and outside the team and that strengthen their ability to face challenges. High
      group emotional intelligence may seem like a simple matter of putting a group of
      emotionally intelligent individuals together. It's not. For a team to have high
      EI, it needs to create norms that establish mutual trust among members, a sense
      of group identity, and a sense of group efficacy. These three conditions are
      essential to a team's effectiveness because they are the foundation of true
      cooperation and collaboration. Group EI isn't a question of dealing with a
      necessary evil--catching emotions as they bubble up and promptly suppressing
      them. It's about bringing emotions deliberately to the surface and understanding
      how they affect the team's work. Group emotional intelligence is about exploring,
      embracing, and ultimately relying on the emotions that are at the core of teams.

PMID- 11246927
TI  - Not all M&As are alike--and that matters.
AB  - Despite all that's been written about mergers and acquisitions, even the experts
      know surprisingly little about them. The author recently headed up a year-long
      study sponsored by Harvard Business School on the subject of M&A activity. In
      depth findings will emerge over the next few years, but the research has already
      revealed some interesting results. Most intriguing is the notion that, although
      academics, consultants, and businesspeople lump M&As together, they represent
      very different strategic activities. Acquisitions occur for the following
      reasons: to deal with overcapacity through consolidation in mature industries; to
      roll up competitors in geographically fragmented industries; to extend into new
      products and markets; as a substitute for R&D; and to exploit eroding industry
      boundaries by inventing an industry. The different strategic intents present
      distinct integration challenges. For instance, if you acquire a company because
      your industry has excess capacity, you have to determine which plants to shut
      down and which people to let go. If, on the other hand, you buy a company because
      it has developed an important technology, your challenge is to keep the
      acquisition's best engineers from jumping ship. These scenarios require the
      acquiring company to engage in nearly opposite managerial behaviors. The author
      explores each type of M&A--its strategic intent and the integration challenges
      created by that intent. He underscores the importance of the acquiring company's
      assessment of the acquired group's culture. Depending on the type of M&A,
      approaches to the culture in place must vary, as will the level to which culture
      interferes with integration. He draws from the experiences of such companies as
      Cisco, Viacom, and BancOne to exemplify the different kinds of M&As.

PMID- 11246928
TI  - Rigor and compassion: the paradoxical challenge of peer review.

PMID- 11246929
TI  - International Conference on Health Research for Development (COHRED), Bangkok,
      Thailand, October 9-13, 2000: report on the symposium on traditional medicine,
      October 9, 2000.

PMID- 11246930
TI  - The White House Commission on Complementary and Alternative Medicine Policy:
      meeting on the Access to, and Delivery of, Complementary and Alternative Medicine
      Services.

PMID- 11246931
TI  - Double standards and double jeopardy for CAM research.

PMID- 11246932
TI  - Valeriana officinalis.

PMID- 11246933
TI  - Assessment of outcomes at alternative medicine cancer clinics: a feasibility
      study.
AB  - OBJECTIVE: This pilot study tested the feasibility of performing outcomes and
      more advanced research regarding cancer patients at two complementary and
      alternative (CAM) clinics. The primary objectives were to determine the
      feasibility of (1) obtaining and collecting data from medical records, (2)
      determining 5-year survival, and (3) comparing 5-year survival to that of
      conventional treatment. In addition, in this paper we present the barriers and
      recommend strategies to facilitate high-quality research. SETTINGS/LOCATION: The
      Bio-Medical Center in Tijuana, Mexico, and the Livingston Foundation Medical
      Center in San Diego, California. SUBJECTS: New patients who were treated for
      cancer during 1992 at the Livingston Foundation Medical Center and during the
      first quarter of 1992 at the Bio-Medical Center. RESULTS: Charts were available
      for 89.6% of the 307 new patients treated at the Bio-Medical Center; 149 (54%)
      patients were treated for cancer and 65 (43.6%) cases were confirmed by pathology
      reports. In contrast, all records were available for 193 new patients treated for
      cancer at the Livingston Clinic; 152 (78.8%) cases had pathology confirmation. At
      both clinics, patients were equally divided by gender and were predominantly
      Caucasian, were married, and were U.S. residents. On average, patients were 51-54
      years old and within 1 year of diagnosis for breast, colorectal, lung, or male
      genital cancer. Most patients (61.1%-63.7%) arrived with distant or regional
      disease after conventional surgery and/or chemotherapy/radiotherapy. Survival at
      5 years was determined for 57.0% at the Bio-Medical Center (11.4% were alive and
      45.6% were deceased) and 94.8% at Livingston (14.5% were alive and 80.3% were
      deceased). The limited number of cases by cancer site prevented comparison to
      conventional treatment. CONCLUSIONS: Historical, widespread use of clinics such
      as these with anecdotal reports of extraordinary survival merit prospective,
      systematic monitoring of patient outcomes. For data to be meaningful, however,
      disease status must be pathologically confirmed and patient follow-up improved.

PMID- 11246934
TI  - Use of orally administered anhydrous crystalline maltose for relief of dry mouth.
AB  - OBJECTIVES: To examine the safety and efficacy of anhydrous crystalline maltose
      (ACM) for treatment of dry mouth. DESIGN: ACM was delivered orally as a 200-mg
      lozenge given three times daily over a 12-week (study Alpha) or 24-week (study
      Omega) period to a total of 22 and 97 subjects, respectively. All participants
      had prominent complaints of persistent dry mouth associated with primary
      Sjogren's syndrome. Patients were examined every 4 weeks in study Alpha and every
      6 weeks in study Omega. SETTINGS: Patients were seen in outpatient clinics at a
      total of 33 sites within the United States. OUTCOME MEASURES: Unstimulated whole
      saliva output, a measure of basal salivary gland function, was determined at each
      visit. Symptoms associated with oral and ocular dryness were assessed at the same
      time with the use of 100-mm visual analog scales. Safety was assessed by physical
      examination and laboratory studies. RESULTS: During these clinical trials, a
      majority of subjects demonstrated an increase in unstimulated whole saliva output
      and the treatment exhibited an excellent safety profile. The ACM treatment in
      study Omega led to significant improvement in several subjective measures of oral
      and ocular comfort. CONCLUSIONS: In these two studies, ACM lozenges administered
      three times daily for 12 or 24 weeks improved salivary output and decreased
      complaints of dry mouth and eyes. Side effects were minimal, and treatment was
      without significant adverse events. This safe and simple intervention may provide
      clinical benefit to individuals with distressing dry mouth symptoms.

PMID- 11246935
TI  - Chronically ill patients treated by spiritual healing improve in quality of life:
      results of a randomized waiting-list controlled study.
AB  - OBJECTIVE: Little is known about the effects of distant healing in chronically
      ill patients, the population most likely to see a healer in practice. This study
      investigated whether distant healing as found in normal practice with patients
      representative of those seeking treatment from healers changes patients' quality
      of life substantially. METHOD: Randomized, waiting-list controlled study of
      distant healing (anonymous, amulet, and allowing for personal contact) in
      chronically ill patients. OUTCOME MEASURE: Patient-reported quality of life as
      expressed by the sum of all MOS SF-36 health survey items. RESULTS: Sixty
      patients were treated by various methods of distant healing over 5 months; 59
      patients were put on a waiting list (control). Quality of life improved
      significantly (p < 0.0005) in the treated group (10 points), while it remained
      stable in the control group. Positive expectation was significantly correlated
      with outcome. CONCLUSION: Chronically ill patients who want to be treated by
      distant healing and know that they are treated improve in quality of life.

PMID- 11246936
TI  - The middle way: realistic randomized controlled trials for the evaluation of
      spiritual healing.

PMID- 11246937
TI  - Static magnetic fields for treatment of fibromyalgia: a randomized controlled
      trial.
AB  - OBJECTIVE: To test effectiveness of static magnetic fields of two different
      configurations, produced by magnetic sleep pads, as adjunctive therapies in
      decreasing patient pain perception and improving functional status in individuals
      with fibromyalgia. DESIGN: Randomized, placebo-controlled, 6-month trial
      conducted from November 1997 through December 1998. SETTING AND SUBJECTS: Adults
      who met the 1990 American College of Rheumatology criteria for fibromyalgia were
      recruited through clinical referral and media announcements and evaluated at a
      university-based clinic. INTERVENTIONS: Subjects in Functional Pad A group used a
      pad for 6 months that provided whole-body exposure to a low, uniform static
      magnetic field of negative polarity. Subjects in the Functional Pad B group used
      a pad for 6 months that exposed them to a low static magnetic field that varied
      spatially and in polarity. Subjects in two Sham groups used pads that were
      identical in appearance and texture to the functional pads but contained inactive
      magnets; these groups were combined for analysis. Subjects in the Usual Care
      group continued with their established treatment regimens. OUTCOME MEASURES:
      Primary outcomes were the change scores at 6 months in the following measures:
      functional status (Fibromyalgia Impact Questionnaire), pain intensity ratings,
      tender point count, and a tender point pain intensity score. RESULTS: There was a
      significant difference among groups in pain intensity ratings (p = 0.03), with
      Functional Pad A group showing the greatest reduction from baseline at 6 months.
      All four groups showed a decline in number of tender points, but differences
      among the groups were not significant (p = 0.72). The functional pad groups
      showed the largest decline in total tender point pain intensity, but overall
      differences were not significant (p = 0.25). Improvement in functional status was
      greatest in the functional pad groups, but differences among groups were not
      significant (p = 0.23). CONCLUSIONS: Although the functional pad groups showed
      improvements in functional status, pain intensity level, tender point count, and
      tender point intensity after 6 months of treatment, with the exception of pain
      intensity level these improvements did not differ significantly from changes in
      the Sham group or in the Usual Care group.

PMID- 11246938
TI  - A case study of misrepresentation of the scientific literature: recent reviews of
      chiropractic.
AB  - Accurate use of published data and references is a cornerstone of the peer-review
      process. Statements, inferences, and conclusions based upon these references
      should logically ensue from the data they contain. When journal articles and
      textbook chapters summarizing the safety and efficacy of particular therapies or
      interventions use references inaccurately or with apparent intent to mislead, the
      integrity of scientific reporting is fundamentally compromised. Ernst et al.'s
      publication on chiropractic include repeated misuse of references, misleading
      statements, highly selective use of certain published papers, failure to refer to
      relevant literature, inaccurate reporting of the contents of published work, and
      errors in citation. Meticulous analysis of some influential negative reviews has
      been carried out to determine the objectivity of the data reported. The
      misrepresentation that became evident deserves full debate and raises serious
      questions about the integrity of the peer-review process and the nature of
      academic misconduct.

PMID- 11246940
TI  - The House of Lords Select Committee's report on CAM.

PMID- 11246939
TI  - Emerging paradigms in mind-body medicine.
AB  - The emerging paradigms in medicine can be seen through mind-body interactions.
      Observations in many meditative traditions suggest a series of objective
      indicators of health beyond absence of disease. Several of the physical signs
      have been confirmed by research or are consistent with modern science. Further
      correlation with long term health outcome is needed. Integration of meditation
      with conventional therapy has enriched psychotherapy with parallels drawn between
      the Nine Step Qigong and Freudian developmental psychology. A unified theory of
      the chakra system and the meridian system widely used in traditional mind-body
      interventions and acupuncture is presented in terms of modern science based on
      the morphogenetic singularity theory. Acupuncture points originate from the
      organizing centers in morphogenesis. Meridians and chakras are related to the
      underdifferentiated, interconnected cellular network that regulates growth and
      physiology. This theory explains the distribution and nonspecific activation of
      organizing centers and acupuncture points; the high electric conductance of the
      meridian system; the polarity effect of electroacupuncture; the side-effect
      profile of acupuncture; and the ontogeny, phylogeny, and physiologic function of
      the meridian system and chakra system. It also successfully predicted several
      findings in conventional biomedical science. These advances have implications in
      many disciplines of medicine.

PMID- 11246941
TI  - Search for medical applications of qigong with the Qigong Database.

PMID- 11246942
TI  - Platelet counting by the RBC/platelet ratio method. A reference method.
AB  - The International Council for Standardization in Haematology (ICSH) and the
      International Society of Laboratory Hematology (ISLH) recommend the counting of
      specifically labeled platelets relative to the RBCs with a fluorescence flow
      cytometer, together with an accurate RBC count determined with a semiautomated,
      single-channel aperture-impedance counter as a reference method for the
      enumeration of platelets. Fresh EDTA-anticoagulated venous blood specimens are
      measured within 4 hours of the draw. The specimen is prediluted (1:20) and the
      platelets labeled with two monoclonal antibodies specific to a cluster of
      differentiation common to all platelets. A final 1:1,000 dilution is made and at
      least 50,000 events with a minimum of 1,000 platelet events are counted with a
      flow cytometer to determine the RBC/platelet ratio. The platelet count is then
      calculated from this ratio and the RBC concentration of the original blood
      specimen.

PMID- 11246944
TI  - Mechanical and thermal properties of gelatin films at different degrees of
      glutaraldehyde crosslinking.
AB  - The mechanical, thermal, swelling and release properties of glutaraldehyde (GTA)
      crosslinked gelatin films have been investigated in order to verify the influence
      of GTA concentration on the stability of the films. Air-dried films were
      submitted to treatment with GTA solutions at concentrations ranging from 0.05 to
      2.5 wt%. At the smallest GTA concentration, the crosslinking degree, determined
      by trinitrobenzensulfonic acid assay, amounts to about 60% and increases up to
      values near 100%, obtained with GTA concentrations > or = 1 wt%. Simultaneously,
      the deformability of the films decreases, whereas the stress at break, sigmab,
      and the Young's modulus, E, increase. A crosslinking degree of about 85%,
      obtained using 0.25% GTA, is enough to prevent gelatin release in buffer solution
      and to provoke a significant reduction of the swelling in physiological solution.
      Furthermore, crosslinking greatly affects the thermal stability of the samples,
      as indicated by the results of differential scanning calorimetry (d.s.c.)
      investigation carried out on wet and air-dried films. The data suggest that the
      use of GTA at low concentration, which is desiderable to prevent toxicity, allows
      to modulate the physico-chemical properties of gelatin films, in order to obtain
      stable materials with a wide range of possible biomedical applications.

PMID- 11246943
TI  - Influence of particle size in the effect of polyethylene on human osteoblastic
      cells.
AB  - The influence of two different sizes of polyethylene particles (< 30 and 20-200
      microm) on osteoblastic function has been studied in primary human bone cell
      cultures. Cells were obtained from trabecular bone fragments of patients
      undergoing knee reconstructive surgery. On reaching confluency, cells were
      subcultured in three flasks: < 30 microm polyethylene particles were added to the
      first flask, 20-200 microm particles to the second flask and none to the third
      flask, which was the control. The resulting subcultures were incubated until
      confluence. Osteoblastic function was evaluated by assaying the secretion of
      osteocalcin, alkaline phosphatase, and C-terminal type I procollagen (PICP), with
      or without 1.25(OH)2D3 stimulation in the cell-conditioned medium. Adding < 30
      microm polyethylene particles to these osteoblastic cell cultures increased the
      levels of osteocalcin secreted after 1,25(OH)2D3 stimulation. Treating stimulated
      or basal osteoblastic cultures with either polyethylene particle size did not
      affect alkaline phosphatase secretion. However, the addition of <30 microm
      polyethylene particles decreased PICP levels in the basal and stimulated
      cultures. A parallel series of osteoblastic cultures was treated with < 30 microm
      polyethylene particles and stimulated or not with 1,25(OH)2D3 to determine the
      effect on osteocalcin mRNA expression using RT-PCR amplification. Polyethylene
      particle-treated cultures had higher osteocalcin mRNA expression regardless of
      whether they had been stimulated with 1,25(OH)2D3 or not. We conclude that
      particle size affects the influence of polyethylene on osteoblastic function
      markers. Particles with a diameter of less than 30 microm increase osteocalcin
      expression and secretion.

PMID- 11246945
TI  - Ocular biomaterials and implants.
AB  - The maintenance of vision is a key determinant of healthy ageing. This has been
      facilitated over recent decades by the development of a wide range of implants
      and biomedical devices to correct the functional deficiencies of disease, age and
      ocular trauma. This brief overview provides an insight into the structure of this
      unique organ, the major physiological functions of the component tissues and the
      present state of the art with respect to modern ocular implants. The review
      focuses primarily on the existing limitations of existing ocular biomaterials
      used in the fabrication of contact lenses, intraocular lenses, glaucoma
      filtration implants, keratoprostheses, intracorneal implants, scleral buckles and
      viscoelastic replacement agents. The challenge of improving ocular compatibility
      and ensuring the longevity of indwelling ocular devices is addressed along with
      the need to improve the physicochemical and mechanical properties of existing
      ocular biomaterials.

PMID- 11246946
TI  - A photoacoustic FTIRS study of the chemical modifications of human dentin
      surfaces: I. Demineralization.
AB  - Acids are used to modify the structure and composition of dentin surfaces to
      improve bonds formed with resins. The purpose of this work is to investigate such
      chemical modifications using the surface-sensitive technique photoacoustic
      Fourier transform infrared spectroscopy (PA-FTIRS). Spectra of acid-treated
      samples (citric, maleic, nitric, and phosphoric at pH = 1.0) were recorded at
      various time intervals. Analysis of these spectra indicates a gradual increase in
      sample surface area with treatment time. A decrease of the bands associated with
      calcium hydroxyapatite (HAP) and carbonate apatite inherent to the mineral phase
      of dentin are also observed. A comparison of spectra of samples treated for 2 min
      with each acid also reveals that maleic and phosphoric acids remove more HAP than
      citric acid. We conclude that citric acid may cause the formation of precipitates
      at the etching front which inhibit etching.

PMID- 11246947
TI  - A photoacoustic FTIRS study of the chemical modifications of human dentin
      surfaces: II. Deproteination.
AB  - This work focuses on the chemical alterations occurring on the dentin surface on
      treatment with sodium hypochlorite (NaOCl), a known deproteinating agent. In
      addition, sequential treatment with both acid and NaOCl are characterized.
      Modifications are evaluated using photoacoustic FTIR (PA-FTIRS), a surface
      sensitive spectroscopy. Spectra of NaOCl-treated dentin samples show a slow and
      heterogeneous removal of its organic phase, leaving calcium hydroxyapatite and
      carbonate apatite unchanged. Spectra of this deproteinated surface resemble those
      of apatites synthesized at low temperatures and having very high-surface areas. A
      combined sequential 2-min treatment of dentin with both maleic acid and NaOCl
      indicates that this treatment can produce a surface region which is neither
      significantly demineralized nor deproteinated. This sequential treatment can be
      used to remove the smear layer and restore the dentin surface to its natural
      composition.

PMID- 11246949
TI  - Chemically formed HAp-Ca poly(vinyl phosphonate) composites.
AB  - The formation of biocompatible organic-inorganic composites by reactions between
      tetracalcium phosphate (Ca4(PO4)2O, TetCP) and the biomedical polymer poly(vinyl
      phosphonic acid) (PVPA) is described. Composites were prepared by hot pressing
      mixtures of these powders at 80 kpsi and 300 degrees C for 30 min. Composite
      formation was investigated depending on the proportions of reactants and the
      processing route used. Two inorganic phases were produced as a result of the acid
      base reaction between TetCP and PVPA: hydroxyapatite (Ca10(PO4)6(OH)2, HAp) and
      anhydrous dicalcium phosphate (CaHPO4, DCPA). The later phase preferentially
      formed at lower TetCP/PVPA ratios while the amount of HAp increased with
      increasing TetCP/PVPA ratio. The reactions appear to start with the softening of
      the polymer when heated to T > Tg. The flowing polymer surrounds the TetCP grains
      permitting the TetCP to initially form DCPA crystallites in a matrix of the Ca
      salt of the polymer. When H2O is added prior to pressing, the DCPA produced
      reacts with the remaining TetCP forming HAp.

PMID- 11246948
TI  - Mechanical properties of a novel PVA hydrogel in shear and unconfined
      compression.
AB  - Poly(vinyl alcohol) (PVA) hydrogels have been proposed as promising biomaterials
      to replace diseased or damaged articular cartilage. A critical barrier to their
      use as load-bearing tissue replacements is a lack of sufficient mechanical
      properties. The purpose of this study was to characterize the functional
      compressive and shear mechanical properties of a novel PVA hydrogel. Two
      formulations of the biomaterial were tested, one with a lower water content (75%
      water), and the other with higher water content (80% water). The compressive
      tangent modulus varied with biomaterial formulation and was found to be
      statistically strain magnitude and rate dependent. Over a strain range of 10-60%,
      the compressive modulus increased from approximately 1-18 MPa, which is within
      the range of the modulus of articular cartilage. The shear tangent modulus (0.1
      0.4 MPa) was also found to be strain magnitude dependent and within the range of
      normal human articular cartilage, but it was not statistically dependent on
      strain rate, This behavior was attributed to the dominance of fluid flow and
      related frictional drag on the viscoelastic behavior. Compressive failure of the
      hydrogels was found to occur between 45 and 60% strain, depending on water
      content.

PMID- 11246950
TI  - Bioactive immobilization of r-hirudin on CVD-coated metallic implant devices.
AB  - The poor biocompatibility of metallic coronary stents which leads to un
      satisfying restenosis rates is mainly caused by contact activation of blood
      cells, smooth muscle cells and endothelial cells. Mimicking a metal surface with
      a biocompatible coating that actively suppresses mechanisms leading to restenosis
      may overcome today's limitations regarding the complications of metal stents.
      Nitinol coronary stents were coated by CVD polymerization of functionalized
      [2.2]paracyclophanes. The monomers 4-amino [2.2]paracyclophane, 4-hydroxy methyl
      [2.2]paracyclophane and [2.2]paracyclophane-4,5,12,13-tetracarboxylic acid
      dianhydride were previously synthesized. A suitable installation for the CVD
      polymerization procedure was designed and used for the polymerization procedures.
      Physical and chemical properties of the polymers were shown to fulfill the
      requirements regarding the application as a stent coating material. The
      functional groups of the polymer coatings were used for the immobilization of the
      thrombin inhibitor r-hirudin. In vitro results indicate that the bioactively
      coated stents are less thrombogenic than virgin metallic stents. Surface-bound r
      hirudin decreases platelet adhesion drastically due to interactions between
      platelets and r-hirudin.

PMID- 11246951
TI  - In vitro study of monocyte viability during the initial adhesion to albumin- and
      fibrinogen-coated surfaces.
AB  - Surface adherent monocytes and macrophages play a central role in the
      inflammatory response to biomaterials. In the present study the adhesion,
      viability and apoptotic changes in material surface adherent monocytes during the
      first hours of cell-surface interactions in vitro were studied, using tissue
      culture polystyrene surfaces coated with human albumin and fibrinogen. Human
      peripheral blood monocytes were enriched by a two-step gradient centrifugation
      and resuspended (1 x 10(6)/ml) in RPMI with 10% fetal bovine serum. The cells
      were added to polystyrene surfaces coated with human fibrinogen or albumin and
      incubated in 37 degrees C (5% CO2, 100% humidity) for 30 min, 1, 2, 3 and 24 h.
      The adherent cells were stained for early apoptotic changes (exposed
      phosphatidylserine) and cell death using Annexin-V-fluorescein and propidium
      iodide staining, respectively. A bi-phasic adhesion was observed on the
      fibrinogen coated surface, having the highest number of adherent cells after 30
      min and 24 h, while the cell number was markedly reduced after 1-3 h. The number
      of adherent cells on albumin was relatively low after all short time incubations
      but had reached a high level after 24 h. The number of adherent dead cells was
      highest after I h on both albumin (approximately 30%) and fibrinogen
      (approximately 15%). In the 24 h cultures, the viability of adherent cells was
      high on both surfaces (95-100%). Viable cells staining positive for early
      apoptotic changes could only be clearly observed on the albumin coated surface,
      after 30 min of cell-material surface interaction. Cell death, including
      apoptotic death, thus seems to play an important role during the initial
      interactions between monocytes and a foreign surface.

PMID- 11246952
TI  - Structure and immersion behavior of plasma-sprayed apatite-matrix coatings.
AB  - The microstructure and properties of a series of plasma-sprayed coatings from
      sinter-granulated powders fabricated from SiO2, CaO, P2O5 and Na2O-containing HA
      composite powders on Ti-6Al-4V substrate were reported. The immersion behavior of
      these coatings in a simulated body fluid (SBF) was also investigated. The results
      showed that sinter-granulated apatite-matrix powders were irregularly shaped and
      appeared quite similar. XRD patterns showed that during fabrication of the
      powders, P2O5 and SiO2 enhanced the decomposition of HA structure, while CaO and
      Na2O did not. Reasonably high bond strengths (45-50 MPa) were obtained from all
      coatings. The plasma spray process itself enhanced the decomposition of apatite
      and chemical reactions among different phases. When immersed in SBF, the
      intensities of such phases as alpha- and beta-TCP in all coatings decreased with
      immersion time and an apatite precipitation took place on all coating surfaces.
      The immersed SiO2- and CaO-containing HA (HSC) coating had the highest rate of
      apatite precipitation among all coatings. The variations in calcium ion
      concentration in simulated body fluid indicated that the HSC-immersed solution
      reached its maximal Ca concentration the earliest, while the HSCP (HA, SiO2, CaO
      and P2O5)-immersed solution reached its maximum the latest.

PMID- 11246953
TI  - Development of a new calcium phosphate cement that contains sodium calcium
      phosphate.
AB  - A cement powder consisting of sodium calcium phosphate, Na3Ca6(PO4)5, in addition
      to tetracalcium phosphate and beta-tricalcium phosphate was prepared by
      pulverizing blocks of 4 wt% sodium-, 11 wt% carbonate-containing apatite samples
      that were heated at 1700 degrees C for 5 h. When mixed with 30 wt% malic acid or
      citric acid at a powder liquid ratio of 3:1, the cement set in 3 or 7 min at room
      temperature with compressive strength being around 52 or 27 MPa. In HeLa-cell
      cultures, the cement mixed with malic acid was less cytotoxic than the cement
      mixed with citric acid, which was far less cytotoxic than a commercial
      carboxylate cement used as a negative control, suggesting malic acid to be
      superior to citric acid as a liquid in this regard. Similar findings were also
      obtained with osteoclasts, of which culture experiments clearly suggested that
      the number of osteoclasts on the cement mixed with malic acid was significantly
      greater than that on the cement mixed with citric acid. Since osteoclastic
      response to substrates could be used as a maker in evaluating their
      bioresorbability associated with osteoclasts, the above finding may suggest that
      the cement that is to be mixed with malic acid would be more useful as bone
      substitutes.

PMID- 11246954
TI  - Films of collagen crosslinked by S-S bonds: preparation and characterization.
AB  - Collagen (type I from calf-skin) was chemically modified by 4-butyrothiolactone
      to obtain the mercapto group-bearing collagen (collagenSH), which possessed SH
      groups in 8-19 M% of a total amino acid residues. The triple helical strands of
      the collagen was not completely perturbed to exhibit the rotary dispersion
      [theta]221, which was as much as 70% of an original intensity of the collagen. In
      the presence of the oxygen dissolved in water, the collagenSH was cross-linked by
      disulfide bonds to afford the collagenSS. The collagenSS could preserve about 15
      and 40% of an original helix structure at 55-70 degrees C and in 2mm sodium
      dodecyl sulfate, respectively. The film made of the collagenSS exhibited the
      tensile strength as high as 36 MPa and was insoluble in most organic solvents
      including water. The collagenSS film was more resistant to degradation by
      collagenase (type I) than the collagen film. The collagenSS film supported the
      growth of L929 fibroblast cell in a manner similar to a collagen film.

PMID- 11246956
TI  - Nuclear methods to characterize biomaterials.
AB  - Techniques using X-rays are often used to study biomaterials fields. However,
      when one is interested by quantitative and very sensitive measurements, it is
      valuable to develop nuclear instruments and methods, in addition and complement
      with others. Fast neutron activation is appropriate for non-destructive analysis.
      Thermal neutron activation can evaluate trace elements as a reference. Proton
      induced X-rays emission is applied to cartography of heavy elements. If
      necessary, proton-induced gamma-rays emission and charged particles scattering
      are suitable for evaluation and cartography of light elements. Radioactivated
      nuclei and labelled molecules can tag element transfers and biofunctionality. In
      our work, these methods are related to biomaterials field.

PMID- 11246955
TI  - Poly(L-lysine)-GRGDS as a biomimetic surface modifier for poly(lactic acid).
AB  - The immobilization of adhesion peptide sequences (such as RGD) at the surfaces of
      poly(alpha-hydroxyacid)s, including poly(lactic acid) (PLA), is complicated by an
      absence of functional groups to support covalent attachment. We demonstrate a
      method to overcome this problem, by attaching the peptide to poly(L-lysine)
      (PLL), which immobilizes the sequence through adsorption at the poly(alpha
      hydroxyacid) surface. When coated using a 0.01% w/v solution of PLL-GRGDS, bovine
      aortic endothelial cells seeded upon the modified PLA showed a marked increase in
      spreading over unmodified PLA. However, inhibition of the cell-spreading effect
      occurred when using higher concentrations of PLL-GRGDS, which we attribute to the
      PLL component. This inhibitory effect can be challenged by increasing the amount
      of GRGDS attached to each PLL molecule. Potentially, this is a flexible method of
      surface modification that can engineer many different types of tissue engineering
      scaffolds with a variety of biomolecules, thus allowing initial cell adhesion to
      be controlled.

PMID- 11246957
TI  - In vitro corrosion resistance of plasma source ion nitrided austenitic stainless
      steels.
AB  - Plasma source ion nitriding has emerged as a low-temperature, low-pressure
      nitriding approach for low-energy implanting nitrogen ions and then diffusing
      them into steel and alloy. In this work, a single high nitrogen face-centered
      cubic (f.c.c.) phase (gammaN) formed on the 1Cr18Ni9Ti and AISI 316L austenitic
      stainless steels with a high nitrogen concentration of about 32 at % was
      characterized using Auger electron spectroscopy, electron probe microanalysis,
      glancing angle X-ray diffraction, and transmission electron microscopy. The
      corrosion resistance of the gammaN-phase layer was studied by the electrochemical
      cyclic polarization measurement in Ringer's solutions buffered to pH from 3.5 to
      7.2 at a temperature of 37 degrees C. No pitting corrosion in the Ringer's
      solutions with pH = 7.2 and 5.5 was detected for the gammaN-phase layers on the
      two stainless steels. The high pitting potential for the gammaN-phase layers is
      higher, about 500 and 600 mV, above that of the two original stainless steels,
      respectively, in the Ringer's solution with pH = 3.5. The corroded surface
      morphologies of the gammaN-phase layers observed by scanning electron microscopy
      are consistent with the results of the electrochemical polarization measurement.

PMID- 11246958
TI  - Evaluation of an in vitro endothelialized vascular graft under pulsatile shear
      stress with a novel radiolabeling procedure.
AB  - OBJECTIVE: To improve the hemocompatibility of vascular grafts, endothelial cell
      (EC) seeding of biomaterials prior to implantation is critical. The current in
      vitro study was designed to investigate such a feasibility on a collagen-coated
      heparin-bonded graft and to evaluate cell detachment upon pulsatile shear stress.
      MATERIALS AND METHODS: Endothelial cells (EA-hy-926) were seeded onto grafts. The
      endothelialization of the grafts was evaluated by the [3H]-thymidine
      incorporation, scanning electron microscopy (SEM) and histological examinations.
      After in situ EC radiolabeling with a novel 99mTc technique, the prostheses were
      exposed to pulsatile shear stress (0.27 N/m2), mimicking the shear rate occurring
      in a superficial femoral artery, for 3 h in a flow circuit and EC loss quantified
      by gamma camera detection. RESULTS: Complete EC coverage was achieved after 5
      days. Three hours of artificial perfusion resulted in a low EC loss (12.9+/-0.8%,
      n = 7). SEM shows EC withstanding shear stress in valleys of prosthesis
      circumvolutions. CONCLUSIONS: These satisfactory results could be explained by
      the high affinity of EC for heparinized surfaces in addition to cell surface
      receptors involved in adhesion to collagen.

PMID- 11246959
TI  - Morphology and metabolism of hepatocytes cultured in Petri dishes on films and in
      non-woven fabrics of hyaluronic acid esters.
AB  - Polymers of hyaluronic acid (Hyal) esters exhibit good tissue compatibility and
      are available in various geometrical configurations. These properties can be
      exploited for the design of innovative bioartificial liver support devices
      (BALSDs) using primary hepatocytes. In this paper, we report a preliminary
      investigation of the polymer feasibility of the ethyl and the benzyl Hyal ester
      in the form of films and non-woven fabrics for the in vitro culture of primary
      rat hepatocytes. Cell function was evaluated daily in Petri dishes with respect
      to the rate of ammonia elimination (AER) and urea synthesis (USR). Cells cultured
      in non-woven fabrics of the ethyl ester of Hyal (HYAFF7nw) exhibited an initial
      AER about 32% lower and synthesised urea 33% faster than that of cells on
      collagen films. After a week in culture, cells on collagen films retained only a
      minor fraction of their initial rates. Cells cultured in non-woven fabrics of
      HYAFF7nw retained about 62 and 44% of their initial AER and USR, respectively,
      and exhibited an AER approximately equal to and a USR 3.6 times greater than
      those of cells adherent to collagen. These results suggest that non-woven fabrics
      of HYAFF7nw are promising substrata for hepatocyte culture in BALSDs.

PMID- 11246960
TI  - Water absorption and surface properties of novel poly(ethylmethacrylate) polymer
      systems for use in bone and cartilage repair.
AB  - The surface and bulk properties of novel methacrylate polymers prepared by
      gelling poly(ethyl methacrylate) (PEMA) powder with different ratios of
      tetrahydrofurfuryl methacrylate (THFMA) and hydroxyethyl methacrylate (HEMA)
      monomers were investigated. The water adsorption and desorption characteristics
      of these polymers were measured in water and phosphate buffered saline (PBS). The
      desorption diffusion coefficients were higher than the adsorption coefficients in
      both water and PBS. Linear relationships between the equilibrium mass of water
      taken up and the mass of water desorbed with the concentration of HEMA in the
      polymer were established. Polymer surfaces were analysed using scanning electron
      microscopy (SEM) and atomic force microscopy (AFM). Surface features varied with
      polymer composition; during hydration only selective areas of the surface
      hydrated indicating a heterogeneous surface. Contact angle data showed no trend
      between the different polymers indicating that contact angles are not an
      acceptable method of assessing hydrophobicity/wettability of a material which
      does not have a homogeneous surface. The effect of these bulk and surface
      characteristics on biological interactions were examined using bovine
      chondrocytes and human osteoblast (HOB) cell cultures. Cell attachment decreased
      when HEMA was present in the copolymer.

PMID- 11246961
TI  - Tissue reaction around metal implants observed by X-ray scanning analytical
      microscopy.
AB  - The soft tissues implanted with Cu, Ni, Fe, Ag, Ti, Ni-Ti, SUS304 and SUS316
      wires were investigated with XSAM and compared with histological observation. The
      relationship between the distribution of dissolved metal elements and the tissue
      response was evaluated. Of the metals whose dissolution was clearly observed by
      XSAM, severe tissue damage was observed around Ni and Cu implants, while fibrous
      connective tissue was formed around the Fe implant. The concentration in
      surrounding tissue was estimated by XSAM using the newly prepared standard
      specimens. The dissolved concentration was approximately 10-20 mm for Ni and Cu
      and was considered to be in the order of ten times higher in Fe. The results
      indicated that the toxicity at the same concentration was from greater Ni > Cu >
      Fe. For Ag, Ti, Ni-Ti, SUS304 and SUS316 implants, significant dissolution and
      severe tissue damage were not observed. The XSAM was especially useful to obtain
      the information of dissolution and distribution behavior of rare content of toxic
      and chemically unstable metals in the soft tissue.

PMID- 11246963
TI  - In vitro dissolution behaviour of two morphologically different thermally sprayed
      hydroxyapatite coatings.
AB  - Two types of hydroxyapatite coating on titanium substrates were produced by
      vacuum plasma spraying and detonation gun spraying. The response of the coatings
      to immersion in Ringer's solution at pH 7.2 and held at 37 degrees C for periods
      of one, two, four and eight weeks was compared. X-ray diffraction was used to
      measure changes in crystallinity and residual stresses. Porosity and coating
      thickness were measured using optical microscopy combined with image analysis.
      Surface morphology was characterised using scanning electron microscopy and
      Talysurf measurements. The DGUN coatings were found initially to have a lower
      crystallinity and porosity but higher surface roughness and residual stress level
      than the VPS coatings. This resulted in a higher rate of dissolution compared to
      the more stable VPS coatings.

PMID- 11246962
TI  - Chitosan microparticles for oral vaccination: preparation, characterization and
      preliminary in vivo uptake studies in murine Peyer's patches.
AB  - Although oral vaccination has numerous advantages over parenteral injection,
      degradation of the vaccine in the gut and low uptake in the lymphoid tissue of
      the gastrointestinal tract still complicate the development of oral vaccines. In
      this study chitosan microparticles were prepared and characterized with respect
      to size, zeta potential, morphology and ovalbumin-loading and -release.
      Furthermore, the in vivo uptake of chitosan microparticles by murine Peyer's
      patches was studied using confocal laser scanning microscopy (CLSM). Chitosan
      microparticles were made according to a precipitation/coacervation method, which
      was found to be reproducible for different batches of chitosan. The chitosan
      microparticles were 4.3+/-0.7 microm in size and positively charged (20+/-1 mV).
      Since only microparticles smaller than 10 microm can be taken up by M-cells of
      Peyer's patches, these microparticles are suitable to serve as vaccination
      systems. CLSM visualization studies showed that the model antigen ovalbumin was
      entrapped within the chitosan microparticles and not only associated to their
      outer surface. These results were verified using field emission scanning electron
      microscopy, which demonstrated the porous structure of the chitosan
      microparticles, thus facilitating the entrapment of ovalbumin in the
      microparticles. Loading studies of the chitosan microparticles with the model
      compound ovalbumin resulted in loading capacities of about 40%. Subsequent
      release studies showed only a very low release of ovalbumin within 4 h and most
      of the ovalbumin (about 90%) remained entrapped in the microparticles. Because
      the prepared chitosan microparticles are biodegradable, this entrapped ovalbumin
      will be released after intracellular digestion in the Peyer's patches. Initial in
      vivo studies demonstrated that fluorescently labeled chitosan microparticles can
      be taken up by the epithelium of the murine Peyer's patches. Since uptake by
      Peyer's patches is an essential step in oral vaccination, these results show that
      the presently developed porous chitosan microparticles are a very promising
      vaccine delivery system.

PMID- 11246964
TI  - Bioactivity in glass/PMMA composites used as drug delivery system.
AB  - Gentamicin sulfate has been incorporated in composites prepared from a SiO2-CaO
      P2O5 bioactive glass and polymethylmethacrylate. Data showed that these materials
      could be used as drug delivery system, keeping the bioactive behavior of the
      glass. The composites supply high doses of the antibiotic during the first hours
      when they are soaked in simulated body fluid (SBF). Thereafter, a slower drug
      release is produced, supplying 'maintenance' doses until the end of the
      experiment. The gentamicin release rate is related with the ionic Ca2+ and H3O+
      exchange between composite and SBF. The porous structure of the composites allows
      the growth of hydroxycarbonate apatite on the surface and into the pores.

PMID- 11246965
TI  - Immobilization of bisphosphonates on surface modified titanium.
AB  - The efficiency of surface modifications on the immobilization of bisphosphonates
      on titanium was investigated with Ca-ion implantation and thin hydroxyapatite
      coatings. The ALP activity of osteoblastic cells and the inhibitory effects on
      the initial adherence of P. gingivalis were also evaluated using bisphosphonate
      immobilized titanium. X-ray photoelectron spectroscopy analysis suggested that
      titanium surfaces modified with Ca-ion implantation and thin hydroxyapatite
      coatings caused the immobilization of bisphosphonate on titanium plates. The ALP
      activity of osteoblastic cells cultured on plates immobilized with bisphosphonate
      was almost the same as that of cells cultured on titanium plates, indicating that
      the bisphosphonate-immobilization showed no toxic effect on osteoblastic cells,
      and that it provides a favorable micro-environment with osteogenetic ability.
      Data of the adherence of oral bacteria showed that a bisphosphonate-immobilized
      titanium surface inhibited the initial adherence of P. gingivalis. These results
      indicate that the immobilization of bisphosphonates on titanium modified with Ca
      ion implantation and thin hydroxyapatite coatings are useful for dental implants.

PMID- 11246966
TI  - Mixed oxides prosthetic ceramic ball heads. Part 3: effect of the ZrO2 fraction
      on the wear of ceramic on ceramic hip joint prostheses. A long-term in vitro wear
      study.
AB  - Using ceramic materials it is possible to obtain a number of beneficial
      mechanical properties such as considerable hardness, good chemical resistance,
      high tensile strength, and a good fracture toughness. The use of ceramic-on
      ceramic as bearing surfaces for hip joint prostheses has been reported to produce
      a lower wear rate than other combinations (i.e. metal-on-polyethylene and ceramic
      on-polyethylene) in total hip artroplasty. These advantages may increase the life
      expectancy of hip implants and improve the life of patients. Two new types of
      mixed-oxide ceramics (alumina and yttria-stabilised zirconia) femoral heads and
      acetabular cups containing different ratios of alumina and zirconia were compared
      with pure commercial alumina in terms of wear behaviour in a hip joint simulator.
      Hip joint wear simulator studies were carried out with a full-peak load of 2030 N
      and a frequency of 1 Hz in bovine calf serum. After 10 million cycles the
      measured weight loss of all specimens was very low. However, the experimental
      results did not show any significant difference between the new experimental
      mixed-oxide ceramics prototype and the commercial ceramic material couplings.

PMID- 11246967
TI  - Biomechanical and histological aspects of fracture healing, stimulated with
      osteogenic protein-1.
AB  - Fracture healing could be stimulated with osteoinductive bone morphogenetic
      proteins (bmp's), such as osteogenic protein-1 (OP-1), but little is known about
      its effectiveness in stimulation of fracture healing. In this study,
      biomechanical and histological aspects of fracture healing after an injection of
      OP-1 in the fracture gap were investigated. In 40 goats, a closed fracture was
      created in the left tibia. The fractures were stabilized with an external fixator
      and the animals were assigned to four different groups: no injection, injection
      of 1 mg OP-1, injection of 1 mg OP-1 with collagenous carrier material, and
      injection of carrier material alone. Twenty-one animals were sacrificed after 2
      weeks and 19 after 4 weeks. Biomechanical testing was perfomed on both explanted
      tibiae. Four longitudinal samples of the fracture were sawn, processed for
      histology, and examined by two observers. Biomechanical evaluation showed a
      higher stiffness and strength at 2 weeks after injection of OP-1. Histological
      evaluation showed normal fracture healing patterns in all animals without adverse
      effects of the given injections. These data show that fracture healing can be
      accelerated with a single injection of OP-1, eventually resulting in normally
      healed bone.

PMID- 11246968
TI  - Local factor production by MG63 osteoblast-like cells in response to surface
      roughness and 1,25-(OH)2D3 is mediated via protein kinase C- and protein kinase A
      dependent pathways.
AB  - Titanium (Ti) surface roughness affects bone formation in vivo and osteoblast
      attachment, proliferation and differentiation in vitro. MG63 cells exhibit
      decreased proliferation and increased differentiation when cultured on rough Ti
      surfaces (Ra > 2 microm) and response to 1,25-(OH)2D3 is enhanced, resulting in
      synergistic increases in TGF-beta1 and PGE2. To examine the hypothesis that
      surface roughness and 1,25-(OH)2D3 exert their effects on local factor production
      through independent, but convergent, signaling pathways, MG63 cells were cultured
      on tissue culture plastic or on smooth (PT, Ra = 0.60 microm) and rough (SLA, Ra
      = 3.97 microm; TPS, Ra = 5.21 microm) Ti disks. At confluence (5 days), cultures
      were treated for 24h with 10(-8) M 1alpha,25-(OH)2D3 and active and latent TGF
      beta1 in the conditioned media measured by ELISA. Cell layers were digested with
      plasmin and released TGF-beta1 was also measured. 1,25-(OH)2D3 regulated the
      distribution of TGF-beta1 between the media and the matrix in a surface-dependent
      manner; the effect was greatest in the matrix of cells cultured on SLA and TPS.
      Inhibition of PKA with H8 for the last 24 h of culture increased PGE2 on SLA and
      TPS, but when present throughout the entire culture period H8 caused an increase
      in PGE2 on all surfaces. 1,25-(OH)2D3 reduced the effect of H8 on PGE2 production
      in cultures treated for 24 h. H8 had no effect on TGF-beta1 in the media by
      itself but caused a complete inhibition of the 1,25-(OH)2D3 dependent increase.
      Inhibition of PKC with chelerythrine increased PGE2 in a surface-dependent manner
      and 1,25-(OH)2D3 reduced the effect of the PKC inhibitor. Chelerythrine also
      increased TGF-beta1 but the effect was not surface dependent; however, 1,25
      (OH)2D3 reduced the effects of chelerythrine with the greatest effects on the
      smooth surface. Thus, the distribution of TGF-beta1 between the media and the
      matrix is regulated by 1,25-(OH)2D3 in a surface-dependent manner. Surface
      roughness exerts its effects on TGF-beta1 production via PKC but not PKA. The
      effect of 1,25-(OH)2D3 on TGF-beta1 production is not via PKC. PKA is involved in
      the surface-dependent regulation of PGE2 but not in the regulation of PGE2 by
      1,25-(OH)2D3 on rough surfaces. Regulation of PKC affects PGE2 production but it
      is not involved in the surface roughness-dependent response to 1,25-(OH)2D3.
      These results suggest two independent but interconnected pathways are involved.

PMID- 11246969
TI  - Expansion behaviour of compomer restoratives.
AB  - This study measured the dimensional changes due to hygroscopic expansion that
      occur in five commercially available compomer restorative materials using a
      computer-controlled laser micrometer. The materials tested were; [C] = Compoglass
      F (Vivadent); [D] = Dyract AP (Dentsply DeTrey); [E] = Elan (Kerr); [F] = F2000
      (3M); [H] = Hytac (Espe). Twelve discs of each test material were prepared, 10 mm
      diameter x 1 mm thickness. All specimens were kept dry for 48 h during
      polymerisation. Two control specimens of each group were kept in a desiccating
      chamber; five specimens in deionized water at 37 degrees C and five specimens in
      artificial saliva (Salivace, Penn) at 37 degrees C. The diameter of each disc was
      measured automatically across 200 points by rotation through the laser beam.
      These measurements, together with weight measurements, were carried out at
      intervals over a 2 month period. At 2 months, the mean % changes in volume after
      water immersion were: [C] = 2.45% (SD = 0.10); [D] = 1.50% (SD = 0.12); [E] =
      1.53% (SD = 0.09); [F] = 1.69% (SD = 0.12); [H] = 1.44% (SD = 0.18). Specimens
      immersed in artificial saliva showed expansion rates identical to those immersed
      in water with the exception of material [H] at 1.73% (SD = 0.02) (p = 0.01). All
      specimens immersed in saliva showed a greater weight gain than those in water.
      The time taken to reach 90% of the final expansion varied from 7 days [F] to 50
      days [H].

PMID- 11246970
TI  - The effect of surface coating on the bond strength of machinable ceramics.
AB  - This study examined the nature of the surface presented by a machinable
      feldspathic porcelain and by a machinable glass-ceramic for bonding to
      conventional composite luting agents and measured the bond strengths which may be
      achieved with various surface treatments. There was no significant difference
      between the bond strengths achieved to etched porcelain, Silicoated porcelain or
      etched glass-ceramic. Silicoated glass-ceramic specimens showed a significantly
      higher adhesive assembly strength (p = 0.02). Examination of the fractured
      specimens showed that in all cases the failure involved part cohesive failure of
      the ceramic surface and part failure at the cement-ceramic interface.

PMID- 11246971
TI  - Localization, regulation, and function of metallothionein-III/growth inhibitory
      factor in the brain.
AB  - The metallothionein (MT) family is a class of low molecular, intracellular, and
      cysteine-rich proteins with a high affinity for metals. Although the first of
      these proteins was discovered nearly 40 years ago, their functional significance
      remains obscure. Four major isoforms (MT-I, MT-II, MT-III, and MT-IV) have been
      identified in mammals. MT-I and MT-II are ubiquitously expressed in various
      organs including the brain, while expression of MT-III and MT-IV is restricted in
      specific organs. MT-III was detected predominantly in the brain, and
      characterized as a central nervous system-specific isomer. The role of MTs in the
      central nervous system has become an intense focus of scientific research. An
      isomer of MTs, MT-III, of particular interest, was originally discovered as a
      growth inhibitory factor, and has been found to be markedly reduced in the brain
      of patients with Alzheimer's disease and several other neurodegenerative
      diseases. MT-III fulfills unique biological roles in homeostasis of the central
      nervous system and in the etiology of neuropathological disorders.

PMID- 11246972
TI  - Galectins, galactoside-binding mammalian lectins: clinical application of multi
      functional proteins.
AB  - Galectins are beta-galactoside binding mammalian lectins and they share
      homologous carbohydrate recognition domains. To date, 11 members of galectin
      family have been cloned and identified. They have been shown to play roles in
      diverse biological events, such as embryogenesis, oncogenesis, adhesion and
      proliferation of the cells, receptor for advanced glycation end products, mRNA
      splicing, bacterial colonization, apoptosis, and in the modulation of the immune
      response. The mechanisms by which galectins exert these diverse effects remain
      largely unknown. However, the elucidation of multi-functional proteins belong to
      galectin family are going to open new fields in clinical science including
      diagnosis and therapy of autoimmune disorders, cancers, and vascular
      complications in diabetes and hypertension.

PMID- 11246973
TI  - The contribution of low affinity NGF receptor (p75NGFR) to delayed neuronal death
      after ischemia in the gerbil hippocampus.
AB  - The implication of low affinity nerve growth factor receptor (p75NGFR), which is
      believed to play a pro-apoptotic role, in delayed neuronal death (DND) after
      ischemia in the gerbil hippocampus was investigated. Immunohistochemistry and
      Western blot analysis revealed that the presence of p75 NGFR immunoreactivity
      (IR) was negligible in the hippocampus of the sham control gerbil but appeared
      clearly in CA1 neurons 3 and 4 days after 5-min transient ischemia. Terminal
      deoxynucleotidyl transferase-mediated UTP nick end labeling (TUNEL) positive
      nuclei appeared when the level of p75NGFR IR increased. Furthermore, almost all
      TUNEL-positive CA1 neurons also costained for p75NGFR. These results suggest that
      p75NGFR contributes to DND after ischemia by an apoptotic mechanism.

PMID- 11246974
TI  - Reduction of ischemic damage by application of insulin-like growth factor-1 in
      rat brain after transient ischemia.
AB  - In order to investigate a possible effect of insulin-like growth factor-1 (IGF-1)
      on ischemic brain injury, IGF-1 was applied topically on the brain surface of
      reperfused rat brain after 60 min of transient middle cerebral artery occlusion.
      In contrast to the cases treated with vehicle, the infarct volume was greatly
      reduced at 24 h of reperfusion by the treatment with IGF-1. Immunohistochemical
      analysis in the middle cerebral artery territory showed that Caspase-3 staining
      was markedly reduced in the cases with IGF-1 treatment, but 72-kDa heat shock
      protein staining remained almost unchanged. The present results suggest that
      treatment with IGF-1 exerts a significant effect on ameliorating brain injury
      after transient focal brain ischemia. Moreover, this effect is greatly associated
      with the reduction of Caspase-3 staining, but is only minimally associated with a
      decreasd stress response at the cellular level.

PMID- 11246975
TI  - Analysis of the immune status in the recipients with long-term well-functioning
      kidneys allografts.
AB  - The immune status of thirteen living and related kidney transplant recipients
      with stable allografts were examined. The immunological assays consisted of a
      mixed lymphocyte reaction (MLR), cell-mediated lympholysis (CML) assay,
      interleukin-2 (IL-2) production in mixed lymphocytes culture (MLC) and IL-2
      receptor (IL-2 R) expression on MLC cells. The suppression rates of the
      monoclonal antibodies (mAbs) against IL-2 R were tested on MLRs. The stimulation
      indices (SI) of the MLR against both donor and third-party cells increased
      compared with those of pretransplantation. The MLC responder cells stimulated by
      donor cells produced detectable amounts of IL-2, these amounts were lower than
      those by third-party cells. The MLC cells against donor cells expressed IL-2 R
      alpha and beta chains to the same degree as those against third-party cells. Anti
      IL-2 R mAbs equally inhibited the MLRs between recipient and donor or third-party
      cells. Cytotoxic T lymphocytes (CTL) against donor cells were not generated, even
      with the addition of recombinant IL-2 in any of recipients except one, while anti
      donor CTL had been detected prior to transplantation and the CTL against third
      party cells were induced in posttranspalnt CML assays. These results indicate
      that the clonal anergy phenomenon might mediate the specific CTL unresponsiveness
      observed in kidney transplant recipients and the anergy phenomenon might serve in
      the long-term acceptance of allograft.

PMID- 11246976
TI  - Experimental study of fast and ultrafast T2-weighted imaging sequences using AMI
      25 superparamagnetic iron oxide (SPIO).
AB  - The objective of this study was to evaluate fast and ultrafast T2-weighted images
      (T2WI), including echo planar imaging (EPI), using an AMI-25 agar phantom. Image
      quality for conventional spin echo (CSE) and turbo spin echo (TSE) was almost
      equivalent. In high-resolution TSE, image quality was highest due to the use of a
      512 x 256 matrix. Half-Fourier single-shot turbo SE (HASTE) was associated with
      blurring of images, and turbo-gradient SE (TGSE) showed a deterioration of image
      quality. EPI also suffered from poor image quality because this method is very
      sensitive to magnetic field inhomogeneity. CSE showed good signal-to-noise ratio
      (S/N) and contrast ratio (CR), but also required the longest imaging times. Among
      the TSE sequences, TSE with a short echo train length (ETL) was superior in terms
      of S/N. The CR of EPI and fast low angle shot (FLASH) images were improved in
      proportion to the effective echo time (TE). At present, TSE is inferior to CSE in
      terms of S/N and CR. However, taking into consideration scanning time, TSE with a
      short ETL is thought to be suitable for routine examinations. Effective TE is an
      important factor in gradient echo (GRE) examinations.

PMID- 11246978
TI  - [Therapeutic guidelines for allergic rhinitis].

PMID- 11246977
TI  - Retroperitoneal liposarcoma presenting a indirect inguinal hernia.
AB  - A 60-year-old man was admitted to our hospital with a right inguinal swelling
      that had been growing in size without any pain for 7 months. We diagnosed the
      growth as a right inguinal hernia and operated on him. The growth, however, was
      found to be a tumor it situated along the spermatic cord and testicular vessels.
      We diagnosed it as a lipoma. The tumor was resected near part of the internal
      inguinal ring. Histopathological diagnosis showed well-differentiated liposarcoma
      of the sclerosing type. Postoperative computed tomography (CT) revealed a large
      residual tumor in the retroperitoneum. We believed that the tumor was a
      retroperitoneal liposarcoma and that it developed in the inguinal region. The
      residue of the liposarcoma was resected onto the right inguinal tract. A periodic
      follow up has been performed and no evidence of recurrence or metastasis has been
      seen in the 4 years and 9 months since the second surgery. No adjuvant therapy
      was performed. Inguinal liposarcomas are relatively rare and in most cases these
      tumors are thought to originate in the spermatic cord. The origin of the tumor is
      believed to be the retroperitoneum.

PMID- 11246979
TI  - [Beta stimulant for asthma treatment].

PMID- 11246980
TI  - [Clinical characteristics of asthmatics who stop peak expiratory flow monitoring
      (PFM)--analysis of patients who continued PFM more than eight weeks].
AB  - To estimate the effect of treatment and for patient education, we recommend 8
      weeks PFM for all asthmatics when we start their treatments. To elucidate
      clinical characteristics of asthmatics who stop PFM, we analyzed 311 patients
      (145 males aged 15-76 years and 166 females aged 17-79 years) who could measure
      their PEFs twice daily for more than 8 consecutive weeks. The analysis of
      cumulative continuation rate of PEF monitoring revealed that the patients'
      withdrawal rate was 19% per year. The sixty asthmatics who gave up monitoring
      their PEFs (group A) showed significantly younger present ages (38.8 +/- 14.2,
      mean +/- S.D.) and younger ages of onset of their asthma (29.8 +/- 19.6) than the
      other 251 asthmatics who could continue to monitor their PEFs (group B). The
      present ages and ages of onset of asthma of group B were 46.2 +/- 16.7 and 37.6
      +/- 21.2 years, respectively. Despite no significant differences in the severity
      of the asthma based on both clinical symptoms and PEF between groups A and B, the
      asthma severity based only on the clinical symptoms of group A were significantly
      less than those of group B. The analysis of Cox's proportional hazards model
      revealed that major factors which influence patients' stopping of PFM were
      present age and severity of their asthma which was estimated by the patients'
      symptoms only, without PEF assessment. These results suggest that asthmatics
      whose present age is young and whose ability of perception of asthma is poor will
      be apt to stop PFM.

PMID- 11246981
TI  - [Relationship between atopic factors and physical symptoms induced by gaseous
      formaldehyde exposure during an anatomy dissection course].
AB  - Formaldehyde (FA) is an occupational and general indoor hazard often affecting
      the respiratory airways. One of the main causes of multiple chemical sensitivity
      is gaseous FA, and it has become an important social problem in developed
      countries. FA concentrations in anatomy dissection classrooms are thought to be
      higher than under usual circumstances. The number of students developing physical
      symptoms during the anatomy dissection course in our university has been
      increasing over recent years. We planned to clarify the causes of such symptoms.
      Ninety-five medical students were interviewed using a questionnaire about
      allergic histories, physical symptoms developed during the anatomy dissection
      course, and symptoms related to chemical sensitivity up to three months after the
      course had finished. We measured total IgE, specific IgE to FA and specific IgE
      to house dust mites. Eighty-three percent of students had experienced symptoms,
      such as burning eyes, nasal discharge, sore throat, general fatigue or skin
      irritation during the course. Fifty percent of students had a past history of
      atopic disease. Fifty-eight percent of students tested positive to specific IgE
      to house dust mites; however, only one student, who did not complain of any
      symptoms during the course, tested positive to FA-IgE. Students with atopic
      factors (present histories of atopic diseases and higher total IgE) and/or
      chemical sensitivity demonstrated worse physical symptoms during the anatomy
      dissection course than students without such histories. In conclusion, it is
      suggested that gaseous FA exposure may exacerbate basic allergic symptoms, and
      moreover that people with chemical sensitivity demonstrated worse symptoms
      following gaseous FA exposure. Nevertheless, in our study we find no relationship
      between FA-IgE and the physical symptoms of gaseous FA exposure during or
      following an anatomy dissection course.

PMID- 11246983
TI  - [A case of systemic scleroderma accompanied by lower leg gangrene].

PMID- 11246984
TI  - [Psychosomatic treatment of allergic disorders].

PMID- 11246982
TI  - [Oral allergy syndrome (OAS) induced by spices with systemic symptoms--also with
      OAS induced by fruits and birch, aler and Japanese cedar pollinosis].

PMID- 11246985
TI  - [Specific inhibition of thrombin activity during cardiopulmonary bypass reduces
      ischemia-reperfusion injury of the lung].
AB  - The pathophysiologic role of thrombin in the development of lung injury after the
      normothermic cardiopulumonary bypass (CPB) was studied in the rabbit model. A
      control group (group D) was subjected to the pericardiotomy without institution
      of CPB. Group A rabbits (n = 6) underwent left heart bypass (80 ml/kg/min) for 60
      minutes without occlusion of the systemic or pulmonary artery and a succeeding
      reduced flow (20-30 ml/kg/min) for another 30 minutes, group B rabbits (n = 6)
      underwent complete CPB (80 ml/kg/min) for 60 minutes in the working mode with
      occlusion of the pulmonary arterial trunk and a succeeding reduced flow without
      occlusion of the pulmonary artery for another 30 minutes, group C rabbits (n = 6)
      underwent the same CPB technique as group B in conjunction with continuous
      intravenous infusion of argatroban (60 micrograms/kg/min), the specific thrombin
      inhibitor. In this group, infusion of argatroban was initiated 60 minutes prior
      to institution of CPB and terminated at the end of the experiment. We sacrificed
      rabbits four hours after the experiment began, and assessed not only
      morphometrically thrombus formation, leukocytic infiltration and luminal
      narrowing of small-sized pulmonary arteries but also immunohistochemically the
      expression of tissue factor (TF) and IL-1 beta, and physico-functionally
      respiratory index (RI) and pulmonary vascular resistance (PVR). Rabbits in group
      A showed multiple occurrence of lung thrombi, luminal narrowing of small
      arteries, and mild infiltration of macrophages and neutrophils positive for TF,
      and, in addition, their RI and PVR became mildly worse. In group B, all these
      morphological and physico-functional parameters became much worse than those
      observed in group A rabbits (p < .01). In contrast, argatroban treatment could
      significantly improve these parameters (p < .01). The expression of TF and IL-1
      beta, however, was not significantly different in group A, B and C. These
      findings indicate that thrombin function intimately participates in the
      development of pulmonary ischemia-reperfusion injury during CPB. In addition, the
      anti-thrombin treatment would be an effective therapeutical tool for the
      prevention of not only activation of extrinsic coagulation pathway but also its
      sequential inflammatory and circulatory disturbance in ischemia-reperfusion
      injury of lung during CPB.

PMID- 11246986
TI  - [3D-MR coronary angiography without breath-hold used for 24 neurosurgical cases].

PMID- 11246987
TI  - [The long-term perfusion system on amylase release from dispersed acinar cells-
      comparative study with direct incubation techinique and residual stimulation].
AB  - We have modified the perfused guinea pig pancreatic acini system in order to
      obtain reproducible results in repeated secretagogue stimulation. No signs of
      tachyphylaxis were observed when cholecystokinin-8 (CCK-8) was administered as
      short pulse for 5 minutes and the interval between administrations were kept more
      than 90 minutes. Maximal amylase response was obtained at 10(-8) M of CCK-8 and a
      supra-maximal significant inhibition on amylase release was observed with higher
      doses of CCK-8. Twenty minutes stimulation with 10(-8) M of CCK-8 showed a
      biphasic response; while, 5 minutes stimulation showed a mono-phasic pattern. The
      results suggest that amylase response was highly influenced not only by the
      concentration of the secretagogue but also the duration of the stimulation in
      this perfusion system. The mechanism of this phenomenon may be comprehensive by
      the double-ligand-complex theory based on low and high affinity site on cell
      surface receptors.

PMID- 11246988
TI  - [Laparoscopic radical nephrectomy for renal cell carcinomas; report on two
      initial cases].
AB  - We recently performed a laparoscopic radical nephrectomy (LRN) on two patients
      with a renal cell carcinoma. Case 1, a 72-year-old man, was diagnosed as having a
      renal cell carcinoma 2.5 cm in diameter in the right kidney, and also a
      submucosal tumor of the cecum. LRN and laparoscopically assisted ileocecal
      resection were performed using a transperitoneal approach on September 28, 1999.
      Total operation time and blood loss during the operation were 308 minutes and 320
      ml, respectively. The operation time needed for LRN, which was calculated as the
      total operation time minus the time spent on ileocecal resection, was 199
      minutes. There were no complications after surgery, and the patient was
      recommended for discharge on the 7th postoperative day, but was actually
      discharged on the 10th postoperative day. Case 2, an 81-year-old man, was
      diagnosed as having a renal cell carcinoma 3.0 cm in diameter in the right
      kidney. He had been undergone a total gastrectomy for a gastric carcinoma at age
      77, and a sigmoidectomy for a sigmoid colon carcinoma at age 79. A
      transperitoneal approach was applied for LRN to detect any recurrence of previous
      carcinomas on September 30, 1999. During adhesiolytic procedures, the colon was
      injured due to an inappropriate maneuver of the grasping forceps. A small
      laparotomy (5 cm) was required for repair of the colon. The total operation time
      and blood loss during surgery were 370 minutes and 850 ml. The operation time
      calculated from the video of LRN was 274 minutes. Two additional surgical
      procedures were required in this case. The first was for a postoperative
      intraperitoneal hemorrhage due to the hemoclip dropping out of the small vein.
      The second was for hemorrhage in the abdominal wall. Fortunately, the clinical
      course after surgery was good and the patient was discharged on the 8th
      postoperative day. There were no complications in case 1. Omitting ileocecal
      resection was considered to speed up oral intake, leading to earlier discharge.
      However, major complications occurred in case 2. It is important to clarify the
      cause of postoperative hemorrhage by careful observation of the video recording,
      in order to suggest safer procedures in laparoscopic surgery. Although these are
      only two LRN experiences, we are convinced that LRN can improve postoperative QOL
      (Quality of life) and is an acceptable alternative for the treatment of renal
      cell carcinomas.

PMID- 11246990
TI  - [Surgery and surgeons in future].

PMID- 11246989
TI  - [A case of traumatic retroperitoneal hematoma with duodenal occlusion].
AB  - A case 67-year old male was admitted with abdominal blunt injury from a traffic
      accident. An abdominal CT revealed a retroperitoneal hematoma behind the pancreas
      head, so we began a conservative therapy of continuous drip while fasting. The
      patient vomited frequently on the 6th day after injury. Upper gastroduodenography
      visualized a narrowing of the descending part of the duodenum. The conservative
      therapy was continued with nasogastric drainage and intravenous fluid.
      Obstructive symptoms disappeared 14 days after the beginning of the therapy. It
      is a rare case that can be considered a candidate for 2 weeks of conservative
      therapy, with no additional damage or peritonitis.

PMID- 11246992
TI  - Doing it for themselves.

PMID- 11246991
TI  - [The C tube in biliary surgery--its development and clinical application].
AB  - BACKGROUND: The T tube procedure for bile drainage after biliary surgery has been
      used all over the world for more than 90 years. However, this method has serious
      drawbacks: a high complication ratio and a need for long-term hospitalization.
      Therefore other bile drainage methods including PTGBD, PTBD and ENBD have been
      developed, but none has so far been able to replace T tube. We have developed a
      new technique for bile drainage using the C tube (cystic duct tube), which is a
      slender tube (6Fr. polyvinyl) inserted via the cystic duct into the common bile
      duct (CBD). We have used C tube in more than 400 cases over the last 20 years:
      for open surgery during the first 10 years, and for laparoscopic surgery in the
      last 10 years. Here we describe the history of improvements in the C tube method
      and the techniques of C tube application in biliary surgery. Elastic surgical
      suture has been used to fix the C tube to the cystic duct, which successfully
      prevented bile leakage from the ductal stump after withdrawal of the tube. C tube
      is not only used for postoperative bile drainage but also for the management of
      remnant stones. The purpose of this study is to assess the safety and benefits of
      the C tube procedure. METHODS: I: From 1980 to 1998, 335 cholecystectomized cases
      which had undergone the C tube procedure were examined for complications
      resulting from C tube placement. II: We analyzed 134 patients with
      choledocholithiasis: 34 patients had been treated using C tube drainage, and 100
      patients had been treated with the T tube procedure after undergoing CBD
      exploration. The main outcome criteria were: the frequency of post-operative
      complications, quantity of bile drainage, drainage period, and length of post
      operative hospital stay. III: Between 1990 and 1999, 131 patients (15.2%) of a
      total of 860 laparoscopically cholecystectomized patients with gallstones
      underwent C tube treatment. We assessed the usefulness of the C tube procedure
      for the detection and management of remnant stones. RESULTS: I: There were no
      major complications (bile-leakage, CBD stenosis, etc.) in 335 cases which
      underwent the C tube procedure. Minor complications related to C tube were:
      spontaneous withdrawal of the tube in 5 cases, movement of the tube tip in 17
      cases, and difficulties during tube removal in 32 cases which included slight
      resistance. Two cases had liver dysfunction (GOT 705 IU/l and 488 IU/l), although
      this was easily normalized after withdrawal of the tube tip from the duodenal
      papillae into the CBD. II: The frequency of complications in patients who
      underwent the C tube procedure was zero, whilst in the T tube group the major
      complication rate was 3% and the minor complication rate was 21%. The quantity of
      bile drainage was 283.6 +/- 22.9 ml/day in the C tube group compared with 302.7
      +/- 10.3 ml/day in the T tube group, showing no significant difference. The
      drainage period (5.9 +/- 0.6 days) in the C tube group was significantly shorter
      than in the T tube group (27.7 +/- 0.9 days). Hospital stays (11.6 +/- 0.6 days)
      in the C tube group were significantly shorter than in the T tube group (45.0 +/-
      1.5 days). III: Remnant CBD stones were detected by postoperative cholangiography
      via the C tube in 28 (21.4%) of the C tube replacement cases and in 3.3% of all
      the laparoscopically cholecystectomized patients. Seventeen patients with remnant
      stones were managed using glyceryl trinitrate CBD perfusion-induced relaxation of
      the sphincter of Oddi. The remaining patients were managed with endoscopic
      papillary balloon dilatation (EPBD) and/or endoscopic sphincterotomy (EST)
      without reoperation. We also have described other applications of the C tube
      procedure for the evaluation of sphincter of Oddi motility as an indication for
      EST, for bile drainage in liver resection, in the treatment of liver injuries,
      and for duodenal decompression after duodenal surgery. Finally we have mentioned
      the possibility of C tube application in the management of obstructive jaundice
      and bile drainage in liver transplantation surgery. CONCLUSION: The C tube method
      in biliary surgery is safe and useful in comparison with the T tube method. We
      are strongly convinced that the T tube will be completely replaced by the C tube.

PMID- 11246993
TI  - Getting through 2 kids.

PMID- 11246994
TI  - Weeds up her bottom.

PMID- 11246995
TI  - Practice makes perfect.

PMID- 11246996
TI  - Interaction between non-ionic contrast medium and prostaglandin E1 incorporated
      in lipid microspheres: in-vitro comparative study of direct and non-direct
      mixing.
AB  - PURPOSE: To examine whether there is any interaction between non-ionic contrast
      medium and prostaglandin E1 incorporated in lipid microspheres (Lipo-PGE1) in
      direct and non-direct mixing. MATERIALS AND METHODS: Iopamidol 300 and 370
      mgI/ml, iohexol 300 and 350 mgI/ml, and iopromide 300 and 370 mgI/ml were mixed
      with Lipo-PGE1. In the direct mixing test, both agents were mixed directly in a
      tube. The appearance of the mixture, average size of the Lipo-PGE1 particles, and
      changes in pH were observed. In the non-direct mixing test, both agents were
      poured one after the other into a narrow luminal glass tube. The appearance of
      the mixture was observed. Lipo-PGE1 and the contrast agent were discharged
      sequentially via a catheter placed in 5 L of physiological saline. The appearance
      of the physiological saline was observed. RESULTS: In the direct mixing test, no
      interaction was observed between iopamidol, iohexol, or iopromide 300 mgI/ml and
      Lipo-PGE1. Aggregation and creaming were observed in the mixture of iopromide 370
      mgI/ml and Lipo-PGE1, and average particle size increased over time. However,
      there was no apparent change in pH. In the non-direct mixing test, none of the
      test contrast agents interacted with Lipo-PGE1. CONCLUSION: The test non-ionic
      contrast media, even if they interacted with Lipo-PGE1 when mixed directly, did
      not appear to interact with Lipo-PGE1 when mixed in a non-direct manner, which
      represents the clinically used prescription in pharmacoangiography.

PMID- 11246997
TI  - Does granulocyte colony-stimulating factor exacerbate radiation-induced acute
      lung injury in rats?
AB  - Radiation pneumonitis (RP) frequently occurs as a complication of thoracic
      irradiation. However, the mechanism of RP is not well known.. Activated
      neutrophils are a possible pathogenesis of RP. Neutrophil activation induced by
      granulocyte colony-stimulating factor (G-CSF) may exacerbate RP. We studied the
      effects of recombinant human G-CSF on acute lung injury induced by thoracic
      irradiation using rats. Animals were divided into three groups: sham irradiation
      with saline control, irradiation alone, and irradiation with G-CSF. Actual
      irradiation was given as a single fraction of 16 Gy delivered to the right
      hemithorax. G-CSF at a dose of 12 microg/body was administered subcutaneously
      once a day from 14 to 18 days after actual irradiation. Lung injury was evaluated
      21 days after irradiation by bronchoalveolar lavage (BAL) fluid findings and the
      lung wet/dry weight (W/D) ratio. Neutrophil and lymphocyte counts in BAL fluid
      and the W/D ratio were significantly increased in the irradiation alone and the
      irradiation with G-CSF groups compared with those of the sham irradiation +
      saline control group. However, there was no significant difference observed
      between the irradiation alone and irradiation with G-CSF groups. In conclusion,
      this study suggests that postradiation administration of G-CSF does not
      exacerbate acute lung injury induced by thoracic irradiation in rats.

PMID- 11246998
TI  - Acute and subacute non-infectious lung diseases: usefulness of HRCT for
      evaluation of activity especially in follow-up.
AB  - PURPOSE: The purpose of this study was to survey the usefulness of high
      resolution CT (HRCT) for the evaluation of activity in acute and subacute non
      infectious diffuse infiltrative lung diseases before and after corticosteroid
      treatment. PATIENTS AND METHODS: Sequential HRCT images and chest radiographs
      obtained before and after treatment were retrospectively evaluated in 33 patients
      with acute or subacute noninfectious diffuse infiltrative lung diseases. All
      these patients were histologically confirmed to have pulmonary Inflammation and
      to have responded to treatment with corticosteroid. Radiographic and CT scores
      were correlated with the degree of dyspnea and the results of arterial blood gas
      analysis using Spearman's rank-correlation coefficient. RESULTS: On follow-up
      HRCT, the profusion score of areas with increased attenuation was significantly
      correlated with arterial oxygen tension (PaO2) (p=.003, r=-.53) and the alveolar
      arterial oxygen tension difference (AaDO2) (p=.001, r=.57). No other correlation
      was found after treatment. Nodular and linear opacities were more commonly seen
      on follow-up chest radiographs and HRCT images than on initial ones. CONCLUSION:
      HRCT is useful for the evaluation of disease activity in acute and subacute
      noninfectious infiltrative lung diseases before and after treatment if paying
      special attention to the profusion of ground-glass attenuation. Even if
      pretreatment HRCT has not been performed, posttreatment HRCT should be examined.

PMID- 11246999
TI  - Flow volume in the common carotid artery detected by color duplex sonography: an
      approach to the normal value and predictability of cerebral blood flow.
AB  - PURPOSE: To determine normal common carotid artery (CCA) flow volume, its
      relationship with age, and the predictability of cerebral blood flow (CBF) by
      color duplex sonography. SUBJECTS AND METHODS: Forty-five healthy subjects (18
      men, 27 women, 23-86 years old) and 13 patients (3 men, 10 women, 51-88 years
      old) without neurological disease underwent color duplex sonography. All 13
      patients also underwent xenon CT. CCA flow volume in the healthy subjects was
      measured to determine normal values. This volume was divided by mean brain weight
      to estimate CBF, which was correlated with CBF measured by xenon CT in regions of
      ipsilateral internal carotid arteries (ICA). RESULTS: In healthy subjects, CCA
      flow volume ranged from 155.0-458.8 ml/min (mean+/-SD: 267.77+/-59.91),
      corresponding to an estimated CBF of 12.43-32.84 ml/min/100 g brain weight
      (mean+/-SD: 20.63+/-4.22). No relationship was found between flow volume and age.
      A good correlation was found between estimated CBF and CBF measured by xenon CT
      in regions of both ICAs (gamma=0.713, p=0.0062 on the left; gamma=0.686, p=0.0096
      on the right). CONCLUSION: By using color duplex sonography, we established a set
      of normal CCA flow volumes, which do not decline with age. Estimated CBF derived
      from flow volume can predict actual CBF.

PMID- 11247000
TI  - Radiotherapy for localized relapse in patients with non-Hodgkin's lymphoma: a
      preliminary report.
AB  - PURPOSE: To evaluate the usefulness of radiotherapy for relapse of non-Hodgkin's
      lymphoma (NHL) at a localized site. METHODS: Of 79 patients with relapsed
      intermediate- or high-grade NHL, 13 patients (16.5%) with a localized relapse
      were analyzed retrospectively. RESULTS: Five patients were treated with
      radiotherapy alone and eight were treated with radiotherapy plus conventional
      chemotherapy (CHOP or other combinations). Radiotherapy was delivered to the
      involved field to a mean total dose of 34.1 Gy (range, 21-51 Gy). The 5-year
      overall and disease-free survival rates were 80.2% and 76.2%, respectively. Four
      patients relapsed subsequently. After further salvage therapy, two patients died
      of NHL and two were alive without active disease. CONCLUSION: Radiotherapy may be
      an important component of treatment for selected patients with NHL who relapse at
      a localized site.

PMID- 11247001
TI  - Usefulness of MR venography in diagnosing sinus pericranii: case report.
AB  - A case of sinus pericranii communicating with the superior sagittal sinus is
      reported. Computed tomography (CT), magnetic resonance (MR) imaging, and
      angiography showed characteristic findings of sinus pericranii. However, MR
      venography was useful to visualize the entire lesion.

PMID- 11247002
TI  - A case of deep soft tissue leiomyoma: CT and MRI findings.
AB  - A 25-year-old man presented with a firm tissue mass of the right elbow and
      intermittent pain. CT showed a dumbbell-shaped soft tissue mass with foci of
      dense calcification in the muscular layer of the triceps brachii muscle and
      subcutaneous tissue. The tumor showed slightly higher signal intensity on T1
      weighted images and markedly higher intensity on T2-weighted images compared with
      the surrounding muscle. Prominent enhancement was present after the intravenous
      injection of Gd-DTPA. Histopathological examination of the resected specimen
      revealed a deep soft tissue leiomyoma.

PMID- 11247003
TI  - Primary ileal volvulus in neonates: radiologic findings in two cases.
AB  - Two cases of primary small bowel volvulus in neonates are presented. On abdominal
      plain radiographs pseudotumor sign was seen in both cases. CT showed intensely
      distended fluid-filled small bowel loops on the right side of the abdomen and
      diffuse distention of the proximal small bowel loops with air-fluid levels. US
      also showed distended fluid-filled loops containing echogenic foci without
      peristalsis. We consider that CT and US can play important roles in the diagnosis
      of small bowel volvulus in neonates.

PMID- 11247004
TI  - Spontaneous rupture of bladder diverticulum after postoperative radiotherapy for
      carcinoma of the uterine cervix: a case report.
AB  - We present a case of spontaneous rupture of bladder diverticulum three years
      after postoperative whole pelvic irradiation (50.4 Gy) for carcinoma of the
      uterine cervix. The patient had suffered from a neurogenic bladder after
      hysterectomy, but excretory urography revealed no abnormalities. Bladder
      diverticulum was found two years later. Spontaneous rupture of the urinary
      bladder is one of the late complications associated with radiotherapy, although
      it is very rare. Postoperative neurogenic bladder may also be associated with
      rupture. We should be aware of this rare complication in patients who receive
      pelvic irradiation.

PMID- 11247005
TI  - Retroperitoneal squamous cell carcinoma: metastasis from uterine endometrial
      carcinoma?
AB  - A case of a retroperitoneal squamous cell carcinoma (SCC) in a 61-year-old woman
      is reported. Imaging studies demonstrated a well-defined solid and cystic mass
      with suggested inferior vena cava (IVC) invasion. She had had a history of
      uterine endometrioid adenocarcinoma (EAC) with squamous differentiation (Grade 1)
      five years previously. Based on the pathological findings, this retroperitoneal
      neoplasm was thought to be a metastasis from the uterine EAC.

PMID- 11247006
TI  - Functional status, medical impairments, and rehabilitation resources in 84
      females with Rett syndrome: a snapshot across the world from the parental
      perspective.
AB  - PURPOSE: Rett syndrome is a neurological disorder almost exclusively affecting
      females. Information on its genetic basis has recently become available. However
      there is little information on the burden and impact of this disorder on the
      family despite the apparent variability in phenotype. The purpose of this study
      was to obtain information on the burden and impact of Rett syndrome by examining
      the functional abilities, medical needs and use of medical, therapy and
      accommodation services in the sample. METHOD: We used the internet to access an
      opportunistic sample of parents of 86 females with Rett syndrome. Data on
      functional status (using the Wee FIM in questionnaire format) morbidity patterns
      and use of services were collected. RESULTS: The response indicated that the
      instrument used would be appropriate for tracking these parameters in a
      population-based cohort. Subjects with Rett syndrome in this pilot sample were
      completely or partially dependent in all functional domains and significantly
      more so than children with Down syndrome. CONCLUSION: The complexity of
      dependency with need for quality medical surveillance throughout adolescence and
      adulthood requires accessible centres of excellence linking families and skilled
      professionals. We plan to use this instrument to obtain a more comprehensive
      profile of the health, functioning and service use of a total population of
      children with Rett syndrome.

PMID- 11247007
TI  - Growth and nutrition in Rett syndrome.
AB  - PURPOSE/METHOD: In this paper we review the existing literature on factors that
      contribute to growth failure in Rett syndrome (RS) with particular emphasis on
      the extent and nature of the feeding difficulties that arise. Data on growth and
      feeding related problems, collected over four years in a specialized clinic for
      females with Rett syndrome are presented and management protocols developed in
      the clinic discussed. RESULTS/CONCLUSION: Feeding related problems and growth
      failure occur commonly in Rett syndrome yet our understanding of the mechanisms
      causing growth failure are poorly understood. Both nutritional and non
      nutritional factors are thought to contribute and it has not been possible to
      develop efficacious intervention strategies. Consequently, clinical management of
      growth failure in Rett syndrome is not evidence based.

PMID- 11247008
TI  - Behavioural and emotional features in Rett syndrome.
AB  - PURPOSE/METHOD: There is increasing agreement that many genetic disorders have
      characteristic behavioural phenotypes; that is genetic anomalies have specific
      effects on behaviour. In this paper the existing literature is reviewed with an
      aim to identify behavioural and emotional features that are candidates for Rett
      syndrome (RS) specific behaviours. RESULT/CONCLUSION: A number of behavioural and
      emotional features have been reported to be common in individuals with RS. These
      behaviours may constitute an RS-specific profile of behaviour or behavioural
      phenotype. Alternatively, these behaviours may simply reflect the multiple
      disabilities found in individuals with severe or profound cognitive impairment.
      The diagnostic criteria for Rett syndrome include a number of the behavioural
      features, such as hand stereotypies and breathing difficulties, although other
      behavioural features are not included.

PMID- 11247009
TI  - Analysis of aberrant behaviour associated with Rett syndrome.
AB  - PURPOSE: The purpose of this study was to identify the variables involved in the
      maintenance of aberrant behaviours associated with Rett syndrome. The occurrence
      of aberrant behaviours associated with Rett syndrome is typically attributed to
      biological variables associated with the disorder. In some cases. however, these
      behaviours have been shown to be sensitive to manipulations of environmental
      variables (i.e. operant contingencies). However, little research exists regarding
      the variables involved in the maintenance of these behaviours and the manner in
      which these variables can be manipulated to effectively reduce the occurrence of
      these behaviours. METHOD: We conducted functional analyses of the aberrant
      behaviours exhibited by two females diagnosed with Rett syndrome. Following the
      functional analyses, treatments were developed to disrupt the relationship
      between the aberrant response and the reinforcer maintaining it. RESULTS: Results
      from the functional analysis suggested that in both cases the aberrant behaviours
      (i.e. hand wringing and hand mouthing) were maintained by automatic
      reinforcement. Treatment, which included interrupting hand wringing for one
      individual and preventing hand mouthing for the other participant, resulted in
      dramatic changes in the levels of aberrant behaviour for both participants. These
      changes suggested that preventing reinforcement delivery reduced the motivation
      to engage in aberrant behaviour. CONCLUSIONS: These results suggest that operant
      variables can be manipulated to influence the occurrence of aberrant behaviour
      associated with Rett syndrome.

PMID- 11247011
TI  - Rett syndrome and ageing: a case study.
AB  - PURPOSE: This case study of an elderly women with Rett syndrome is used to
      consider whether observed changes may be related to physiological processes
      involved in ageing or environmental adaptations, which is important for delivery
      of rehabilitation. METHOD: The life story of a woman with Rett syndrome who lived
      to the age of 60 is presented. It is based on medical records, older and more
      recent videotapes, and interviews with her sister and care staff. RESULTS: After
      21 years without walking, following intensive physiotherapy, she regained the
      ability to walk without support. She also showed improvement in hand use a few
      years before she died. During the early regression she appeared to lose social
      interest. The interest improved after some time, but she remained wary of people
      she did not know. CONCLUSION: The walking and hand use indicate that these
      functions may have been present to a greater extent than assumed by people in the
      environment and that her poor function reflects dyspraxia and lack of opportunity
      and training rather than lack of ability. Although more studies of elderly women
      with Rett syndrome is needed to answer whether the observed changes were due to
      physiological processes involved in ageing or environmental adaptations, the
      present case story demonstrates that identification of females with Rett syndrome
      is important at all age levels.

PMID- 11247010
TI  - Storybook-based communication intervention for girls with Rett syndrome and their
      mothers.
AB  - PURPOSE: Storybook reading provides a natural language learning context in which
      to support early symbolic communication. In this study, we explored the impact of
      (1) resting hand splints, (2) light tech augmentative communication systems such
      as voice-output devices and symbols, and (3) very basic parent training on the
      symbolic communication and labelling behaviours of six girls with Rett syndrome.
      METHOD: Mothers and daughters were videotaped as they read familiar and
      unfamiliar storybooks in their homes. RESULTS: Group and individual data
      collected from the six girls indicated that they became more active and
      successful participants in the interactions during storybook reading. The girls
      employed a wider range of communication modes and increased the frequency of
      their labelling. Familiar storybook reading encouraged greater symbolic
      communication than unfamiliar storybooks in half the girls. CONCLUSION: This
      study suggests that motivated parents may not require expensive technologies or
      lengthy training in order to enhance their children's early communication and
      participation in storybook reading.

PMID- 11247012
TI  - Having friends and Rett syndrome: how social relationships create meaningful
      contexts for limited skills.
AB  - PURPOSE: The experiences of a teenage girl with Rett syndrome who was being
      educated in an inclusive middle school are described to provide a better
      understanding of how social relationships create meaningful contexts for
      individuals with limited skills. The case example is used to illustrate the
      principle that contexts (including expectancies, acceptance, philosophical
      principles) can be designed to support meaningful social relationships, despite
      social and intellectual disabilities. METHOD: Naturalistic observations of social
      interactions over a two year period are reported to illustrate the possible types
      of social relationship between this young person and her adolescent friends and
      peers. RESULTS/CONCLUSIONS: While someone with this syndrome might be judged
      objectively to have minimal social skills, an accepting social environment
      willing to read minimal communicative cues provided the context for many typical
      social interactions. Since contexts require subjective judgement. the post-modern
      concept that disability represents a social construction can be viewed as a
      metaphor compatible with the reality that careful planning and structuring of the
      environment is in some instances the most appropriate intervention focus rather
      than the person with a disability. The sorts of positive friendship experiences
      described in this paper did not occur spontaneously, or by chance alone, nor were
      they the result of social skills instruction. Instead, they were associated with
      observable social behaviour by caregivers and peers who were extending their own
      repertoires to accommodate someone objectively determined to have a severe
      disability.

PMID- 11247013
TI  - Special issue on Rett syndrome.

PMID- 11247014
TI  - Rett syndrome: clinical characteristics and recent genetic advances.
AB  - PURPOSE: Rett syndrome is a neurodevelopmental disorder that occurs almost
      exclusively in females. In recent years there has been increased knowledge
      concerning the multidisciplinary management of individuals with Rett syndrome.
      The aim of this paper is to provide an update of the clinical phenotype, natural
      history and current genetic understanding of the disorder. RESULTS/CONCLUSION:
      Rett syndrome is thought to be the second most common cause of severe mental
      retardation in females after Down syndrome. it now appears that females with RS
      present with a much broader phenotype than originally described. Recently,
      mutations in the MECP2 gene encoding X-linked methyl-CpG-binding-protein 2 have
      been identified in some females with Rett syndrome.

PMID- 11247015
TI  - [Prophylaxis of venous thromboembolic complications in patients operated on
      abdominal organs].
AB  - Comparative analysis of results of venous thromboembolic complications
      prophylaxis (deep vein thrombosis--DVT1, pulmonary artery thromboembolism--PAT)
      in patients operated on abdominal organs during two periods--from 1980 to 1983
      (when traditional methods were used--leg bandage, rarely--0.25-0.5 g aspirin 1-2
      times a day 5-8 days after surgery) and from 1984 to 1998 (when in the operated
      patients with moderate, high and very high risk of DVT and PAT combination of
      physical methods of blood flow acceleration in leg deep veins with drugs was used
      -minidoses or individually selected doses of non-fractionated heparin, low
      molecular heparin, dextrans) was carried out. Compared with first period the rate
      of manifested DVT decreased from 1 to 0.3%, fatal PAT (percentage of those who
      died from all operated)--from 0.3% in 1982-1983 to 0.026% in 1998, i.e. more than
      10 times. In some years (1992-1993) there were no lethal outcomes of PAT.

PMID- 11247016
TI  - [Main principals of clinical diagnosis formation in peritonitis].
AB  - Based on great clinical experience (more 1000 patients) the author makes attempt
      to standardize classification of peritonitis. Bearing in mind the critical
      analysis of available peritonitis classifications, it is proposed to divide toxic
      phase of peritonitis (by K.S. Simonyan) into two variants--with poliorganic
      insufficiency or without it. This elaboration permits to make the treatment of
      the patients with general peritonitis more detailed. Besides, the changes were
      made in division of peritonitis by degree of generalization along peritoneum, it
      is proposed to distinguish only 4 types by abdominal exudate character that also
      determine the actions of surgeon. Individual surgical situations in various forms
      and types of peritonitis are analyzed. The own model of peritonitis
      classification permits to receive comparable immediate results of treatment.

PMID- 11247017
TI  - [Eventrations after median laparotomies].
AB  - The proposed method of eventration treatment was used in 7 patients with a
      positive effect. The main element of this method is guiding Kirschner's wires
      through sheath of the rectus abdominis. The method may be used for prophylaxis of
      eventration if indicated. It has some advantages over other methods and can be
      recommended for use in surgical practice.

PMID- 11247018
TI  - [Surgical treatment of patients with purulent cholangitis in cholelithiasis].
AB  - Results of treatment of 89 patients with cholelithiasis complicated by
      obstructive jaundice and purulent cholangitis using the minimally invasive
      technologies are analyzed. The advantages of two-stages surgical treatment of
      these patients are demonstrated. The decompression of biliary tract are performed
      as the first stage, radical operations by laparoscopy or minilaparotomy--as the
      second stage. This method permits to refuse the large and traumatic operations
      and to improve significantly the nearest and long-term results of treatment.

PMID- 11247019
TI  - [Anatomic resection of spleen in experiment].
AB  - The study was carried out in 35 dogs. Basic surgical techniques developed
      experimentally for organ-saving operations on the spleen are presented. Methods
      of lobar and segmental resections of the spleen based on detailed study of
      variants of branching of splenic artery and vein are described. Angiography
      visualized sharply splenic arteries after lobar and segmental resections,
      including the stumps of transected arteries. Ultrasonic examination, performed
      before operation and in different terms after it (3-360 days), specified the
      size, shape echostructure and anatomic relationship of the spleen with adjacent
      organs before and after operation.

PMID- 11247020
TI  - [Surgical treatment of hepatic echinococcosis and its complications].
AB  - Over 11 years 280 patients underwent surgery for hepatic echinococcosis. A
      complicated form of the disease was revealed in 151 (54%) patients. Suppuration
      of cyst was in 88 (31.4%) patients, perforation of cyst into biliary tract--in 87
      (31.1%), compression of bile ducts by cyst with mechanical jaundice--in 5 (1.8%),
      perforation into abdominal cavity--in 2 (0.7%) and cyst's calcification--in 9
      (3.2%). The diagnosis was based on clinical, objective and instrumental
      examinations. The most informative methods in diagnosis of hepatic echinococcosis
      were US (96.7%) and CT (100%). Radical operations were performed in 26 patients:
      pericystectomy--6, "ideal" echinococcectomy--11, resection of the liver--9. In
      true bursting of parasite's elements into biliary tract with mechanical jaundice
      and cholangitis, the correction of biliary tract's passability was carried out.
      Postoperative complications were revealed in 33.2% patients, in the most cases
      they were non-specific. Lethality was 1.7% (3 patients).

PMID- 11247021
TI  - [Laparoscopic operations in acute adhesive intestinal obstruction in children].
AB  - Results of treatment of 148 children suspected for acute adhesive intestinal
      obstruction (AAIO) after laparoscopy are analyzed. Age of the patients ranged
      from 3 weeks to 14 years. There were 90 (61.4%) boys and 58 (38.6%) girls.
      Diagnosis of AAIO was confirmed in 129 patients (other diseases were revealed in
      19 children). Laparoscopic adhesiotomy was impossible in 13 cases because of
      contraindications (necrosis of strangulated intestine, abscess-forming
      infiltration, general adhesive process). Laparoscopy was performed by specially
      developed technique decreasing the risk of examination in the conditions of
      adhesive process. The contraindications to laparoscopic adhesiotomy were
      developed. Laparoscopy permitted to remove the obstruction in 79.8% patients with
      AAIO. There was one intraoperative complication--colon injury in the area of
      earlier spontaneously closed fistula (laparotomy and suturing of colon's defect
      were performed). Postoperative period after laparoscopic operations was easier
      than after open operations: physical activity of the patients recovered quickly,
      number of postoperative complications decreased more than 3 times, hospital stay
      reduced more than 2 times. There were no lethal outcomes.

PMID- 11247022
TI  - [Organ-saving operations in different localization of breast cancer].
AB  - Two methods of filling breast defects after radical resection for nodular cancer
      located in inner and low quadrants were developed allowing to perform axillary
      lymphadenectomy without additional axillary approach (patents No. 2125408 and No.
      2127552). The methods are based on transposition of breast skin flaps. These
      methods have been used in 43 patients: in 31 women with T1-2N0 M0 stage, in 12
      women T1-2N1-2M0, and with breast size B(2)--in 8, C(3)--in 30, D-E(4-5)--in 5
      patients. Flap's marginal necrosis was in 3 patients only. Cosmetic results were
      excellent and good in 72.1% of operated patients.

PMID- 11247023
TI  - [Importance of lower limbs diabetic angioneuropathy classification ].
AB  - The author proposes classification which determines continuity in the treatment
      of patients with lower limbs diabetic angioneuropathy. In working classification
      the stage of disease (compensation, decompensation), form (with or without major
      circulation disorder), type (complicated, uncomplicated) are taken into account.
      The proposed classification solves tactical, diagnostic and curative problems.
      This permitted to decrease the rate of amputations from 32 to 5.7% and lethality
      from 15 to 3.5%.

PMID- 11247025
TI  - [Extended left-sided resection of liver in hamartoma rupture].

PMID- 11247024
TI  - [Combined treatment of purulent-necrotic lesions of lower extremities in diabetic
      patients].
AB  - Combined treatment of pyonecrotic focus and purulent see pages on foot by means
      of permanent abacterial medium creation was performed in 38 patients with
      decompensated diabetic ischemia of lower extremities. 2% boric acid was used as
      antiseptic (affected foot was immersed in the solution). Local use of this medium
      during 7-10 days with sodium succinate and other modern drugs administration
      permits to decrease lethality to 7.9%, rate of high amputations--to 5.3% (mean
      hospital stay was 24.6 +/- 0.83 bed days).

PMID- 11247026
TI  - [Prediction of vagotomy results].

PMID- 11247027
TI  - [Drainage and lavage of abdominal cavity and hollow gastrointestinal tract organs
      in the treatment of peritonitis].

PMID- 11247028
TI  - [Hepatic echinococcosis complicated by cystobiliary fistula].

PMID- 11247029
TI  - [Role of bacterial translocation in pathogenesis of surgical infection].

PMID- 11247030
TI  - [Biopsy of non-palpable tumors of the breast].
AB  - 14 biopsies were performed in patients with non-palpable tumors of the breast
      with stereotaxic automated system (ABBI) and disposable "pistol-needle" ("Auto
      Suture") whose needle-harpoon penetrates into pathologic focus under local
      anesthesia (four fold digital stereotaxic control guarantees the precision of
      biopsy). Non-palpable breast cancer in the tissue areas of 4, 7 and 11 mm in
      horizontal section was diagnosed in 3 patients. Biopsy was performed
      outpatiently, there were no complications. The procedure is like a diagnostic
      sectoral resection of the breast.

PMID- 11247031
TI  - [Diagnosis and surgical treatment of penetrating duodenal ulcer].
AB  - The results of complex diagnosis and surgical treatment of 152 patients with
      penetrating duodenal ulcer were analyzed. The disease is accompanied by chronic
      recurrent pancreatitis in 80.5% of them. Organo-saving operations with vagotomy
      and duodenoplasty have an advantage over resection methods in patients with
      penetrating duodenal ulcer combined with chronic recurrent pancreatitis.

PMID- 11247032
TI  - Cadmium biosorption by a cadmium resistant strain of Bacillus thuringiensis:
      regulation and optimization of cell surface affinity for metal cations.
AB  - A marine bacterial strain putatively identified as Bacillus thuringiensis strain
      DM55, showed multiple heavy metal resistance and biosorption phenotypes. Electron
      microscopic studies revealed that DM55 cells are encased in anionic cell wall
      polymers that can immobilize discrete aggregates of cations. Factors affecting
      cell surface affinity for metal cations, monitored by means of Cd2+ binding
      capability, are investigated. The mechanisms of cadmium resistance and Cd2+
      biosorption by the bacterium appeared to be inducible and coincident. Medium
      components affecting metal removal under cadmium-stressed growth conditions were
      explored based on the application of two sequential multi-factorial statistical
      designs. Concentrations of potassium phosphates and peptone were the most
      significant variables. Optimized culture conditions allowed DM55 cells grown in
      the presence of 0.25 mM CdCl2 to remove about 79% of the metal ions within 24 h
      with a specific biosorption capacity of 21.57 mg g(-1) of biomass. Both fresh and
      dry cells of DM55 prepared under cadmium-free optimal nutrient condition were
      also able to biosorb Cd2+. In addition to the concentration of phosphate in the
      medium, KinA, a major phosphate provider in the phosphorelay of Bacillus cells,
      was also demonstrated to regulate the magnitude of cell surface affinity for
      cadmium ions.

PMID- 11247033
TI  - Role of conserved histidine residues in metalloactivation of the ArsA ATPase.
AB  - The ArsA ATPase is the catalytic subunit of a pump that is responsible for
      resistance to arsenicals and antimonials in Escherichia coli. Arsenite or
      antimonite allosterically activates the ArsA ATPase activity. ArsA homologues
      from eubacteria, archaea and eukarya have a signature sequence (DTAPTGHT) that
      includes a conserved histidine. The ArsA ATPase has two such conserved motifs,
      one in the NH2-terminal (Al) half and the other in the COOH-terminal (A2) half of
      the protein. These sequences have been proposed to be signal transduction domains
      that transmit the information of metal occupancy at the allosteric to the
      catalytic site to activate ATP hydrolysis. The role of the conserved residues
      His148 and His453, which reside in the A1 and A2 signal transduction domains
      respectively, was investigated by mutagenesis to create H148A, H453A or
      H148A/H453A ArsAs. Each altered protein exhibited a decrease in the Vmax of
      metalloid-activated ATP hydrolysis, in the order wild type
      ArsA>H148A>H453A>H148A/H453A. These results suggest that the histidine residues
      play a role in transmission of the signal between the catalytic and allosteric
      sites.

PMID- 11247034
TI  - Removal of catalytic activity by EDTA from antibody light chain.
AB  - Gp41 peptide antigen of the HIV-1 envelope (TP41-1:TPRGPDRPEGIEEEGGERDR, a highly
      conserved region) was enzymatically degraded by the antibody light chain 41S-2-L
      after an induction period. The peptide bond between Glu14 and Gly15 was cleaved
      early in the reaction. When EDTA was added in the induction period, it inhibited
      the degradation of TP41-1 thus ceasing the catalytic activity of 41S-2-L. In
      contrast, when EDTA was added after the induction period, only a small reduction
      in the catalytic activity was observed. These observations suggest that metal
      ions are important in stimulating catalytic activity early in the reaction.

PMID- 11247035
TI  - Kinetic studies of the reactions of some metal reconstituted metallothioneins
      with the electrophilic disulfide 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB).
AB  - Rabbit liver Pt7MT, Zn7MT, Bi7MT were reconstituted and the kinetic studies of
      the reactions with electrophilic disulphide 5, 5'-dithiobis-(2-nitrobenzoic acid)
      (DTNB) were investigated to explore the possible mechanism of metals release from
      metallothioneins. It is revealed that the Pt7MT, Zn7MT react with DTNB
      biphasically, yielding a four-term rate law: Rate = k1f [MT] + k2f [DTNB][MT] +
      k1s [MT] + k2s [DTNB][MT]. Zn7MT reacts with disulphide DTNB more rapidly and has
      significantly greater observed rate constants ks, kf than Pt7MT. The kinetic data
      for Bi7MT indicate that the reaction is monophasic and the rate law is proved to
      be: Rate = k1 [MT] + k2 [DTNB][MT]. The observed pseudo-first order rate
      constants for above MTs are insensitive to pH value. Based on the available
      experimental data, the different kinetic behaviors of MTs reactions with
      electrophilic disulphide DTNB and a possible mechanism to release the coordinated
      metal ions are discussed.

PMID- 11247036
TI  - The structure of a pyoverdine from Pseudomonas sp. CFML 96.188 and its relation
      to other pyoverdines with a cyclic C-terminus.
AB  - From Pseudomonas sp. CFML 96.188 a pyoverdine was isolated and its primary
      structure was elucidated by spectroscopic methods and degradation reactions. This
      strain is of interest as it accepts the structurally different pyoverdines from
      several other Pseudomonas strains. They all have in common as a specific
      structural feature a C-terminal cyclic substructure, the importance of which for
      the recognition of a pyoverdine at the cell surface of a given strain will be
      discussed.

PMID- 11247037
TI  - Cadmium concentration in blood in an elderly urban population.
AB  - Concentration of cadmium in blood in an elderly population with a mean age of 87
      years was studied in relation to age, blood pressure, BMI, cognitive function,
      gender and smoking. This population-based study consisted of 804 subjects both
      men and women. Clinical examination included medical and social history, physical
      and neurologic examination, and assessment of cognitive functions with Mini
      Mental State Examination (MMSE). Information on prescription and non-prescription
      drug use was collected. Anti-hypertensive drugs included all medicines
      potentially used for treating high blood pressure. Blood pressure was measured.
      Whole blood from 763 subjects was analysed for cadmium by atomic absorption
      spectrophotometry (GFAAS) with Zeeman background correction and with a graphite
      furnace using the L'vov platform technique including quality control. Differences
      in cadmium concentrations were related to non-smokers (3.9 nmol/l), previous
      smokers (4.4 nmol/l) and current smokers (7.5 nmol/l). There were no relations
      between cadmium and age, blood pressure or cognitive functions. In conclusion,
      increased cadmium levels were found in smokers. A possible contribution from
      previous occupational exposure needs to be further evaluated.

PMID- 11247038
TI  - Biochemical properties of canine serum ferritin: iron content and nonbinding to
      concanavalin A.
AB  - A sandwich enzyme-linked immunosorbent assay using H-subunit-rich canine heart
      ferritin as a standard has been developed for measuring canine serum ferritin
      which is H-subunit-rich. Serum ferritin concentrations in 51 normal dogs ranged
      from 143 to 1766 ng ml(-1), with a mean value of 479 +/- 286 (SD) ng ml(-1).
      Serum ferritin iron concentrations as determined by an immunoprecipitation
      technique ranged from 30.4 to 115.9 ng ml(-1) in 15 normal dogs with serum
      ferritin protein levels of 298 to 959 ng ml(-1). There was a significant linear
      correlation between the serum ferritin iron and protein levels (r=0.9441,
      P<0.001), and the mean iron/protein ratio of serum ferritin was 0.112 +/- 0.017.
      When canine sera were incubated with concanavalin A-Sepharose 4B, we observed the
      apparent binding of serum ferritin to concanavalin A. However, ferritin obtained
      by heat-treating the sera at pH 4.8 to remove the ferritin-binding proteins did
      not bind to the lectin. These results suggest that canine serum ferritin contains
      a considerable amount of iron but no concanavalin A-binding G subunit present in
      human serum ferritin.

PMID- 11247039
TI  - Superparamagnetic magnetite in the upper beak tissue of homing pigeons.
AB  - Homing pigeons have been subject of various studies trying to detect magnetic
      material which might be involved in magnetic field perception. Here we focus on
      the upper-beak skin of homing pigeons, a region that has previously been shown to
      contain nerves sensitive to changes of the ambient magnetic field. We localized
      Fe3+ concentrations in the subcutis and identified the material by transmission
      electronmicroscopy (TEM) as aggregates of magnetite nanocrystals (with grain
      sizes between 1 and 5 nm). The particles form clusters of 1-3 microm diameter,
      which are arranged in distinct coherent elongated structures, associated with
      nervous tissue and located between fat cells. Complementary low-temperature
      magnetic measurements confirm the microscopic observations of fine-grained
      superparamagnetic particles in the tissue. Neither electron-microscopic nor
      magnetic measurements revealed any single-domain magnetite in the upper-beak skin
      tissue.

PMID- 11247040
TI  - New synthetic catecholate-type siderophores based on amino acids and dipeptides.
AB  - New analogs of bacterial siderophores with one, two or three catecholate moieties
      were synthesized using various mono- and diamino acid and dipetide scaffolds,
      respectively. In addition to 2,3-dihydroxybenzoyl siderophore analogs and their
      acylated derivatives, 3,4-dihydroxybenzoyl derivatives were prepared.
      Furthermore, the synthesis of a new triscatecholate serving as an intimate model
      for enterobactin is reported. Most of the new compounds gave a positive CAS-test
      and were active as siderophores tested by growth promotion assays with a set of
      siderophore indicator mutants under iron limitation. Structure-activity
      correlations have also been studied.

PMID- 11247041
TI  - Complexation of peptide with Cu2+ responsible to inducing and enhancing the
      formation of alpha-helix conformation.
AB  - Role of some metal ions on the conformations of peptides was examined by using a
      series of short alanine-based peptides with single Trp-His (W-H) interaction in
      different environments. Circular dichroism (CD), Trp (W) fluorescence emission,
      and Fourier transform infrared (FTIR) spectroscopy revealed that there is a
      conformational role of Cu2+ in inducing and enhancing the formation of alpha
      helix conformation. The complexation of the peptide with Cu2+ is responsible to
      the conformational effect because the chelation is able to stabilize peptide with
      an alpha-helix conformation. The possible factors affecting the role of Cu2+ are
      discussed in the paper. The results in this paper are useful to understand the
      important structural role of Cu2+ in protein folding and the possible mechanism
      in some neurodegenerative diseases such as Alzheimer's disease.

PMID- 11247042
TI  - Relation between trace element levels in plasma and myocardium during
      coxsackievirus B3 myocarditis in the mouse.
AB  - During most infections the plasma levels of trace elements change, but it is not
      clear if this reflects changes in the infected tissues. Coxsackievirus B3 (CB3)
      infection may result in viral replication, subsequent inflammation and changed
      trace element levels in the myocardium. In the present study, the trace element
      levels in the plasma and heart of adult male A/J mice were determined during the
      pre-inflammatory stage (day 4) of CB3 myocarditis for the following trace
      elements: aluminium (Al), arsenic (As), calcium (Ca), cobalt (Co), copper (Cu),
      iron (Fe), magnesium (Mg), manganese (Mn), selenium (Se), silver (Ag), vanadium
      (V) and zinc (Zn). The severity of the infection was assessed through clinical
      signs of disease and trace element levels were measured through inductively
      coupled plasma mass-spectrometry (ICP-MS). In the heart, the levels decreased for
      V (59%; p < 0.01), Co (38%; p < 0.01), Al (81%; p < 0.01), As (66%; p < 0.01) and
      Se (16%; p < 0.01). Increased levels were detected for Mn (13%; p < 0.05), Fe
      (48%; p < 0.01), Cu (34%; p < 0.01) and Ag (46%; p < 0.01). In the plasma,
      decreases were detected in the level of Zn (32%; p < 0.05), whereas increases
      were seen in Mn (362%; p < 0.05), Fe (272%; p < 0.01), Co (71%; p < 0.05), Cu
      (25%; n.s.) and Mg (43%; p < 0.01) levels. A correlation was found between the
      levels in plasma and myocardium for Co (r(s) = -0.636; p < 0.05), Fe (r(s) =
      0.764; p < 0.05), Mn (r(s) = 0.682; p < 0.05) and Mg (r(s) = -0.791; p < 0.05).
      Thus, determination of some of these trace elements in the plasma may be useful
      to indicate target tissue involvement in the early pre- inflammatory stage of an
      infectious disease. Some of these elements are important nutrients for the immune
      system, while others may be associated with the development of disease
      complications, such as cardiac arrhythmias.

PMID- 11247044
TI  - Maedi-visna virus, a model for in vitro testing of potential anti-HIV drugs.
AB  - A series of beta-D- and beta-L-cytidine analogues were evaluated for their
      inhibitory effect on the replication of maedi-visna virus (MVV) strains KV1772
      and MV1514 cultured on sheep choroid plexus cells and the sheep chondrocyte cell
      line G81092, respectively. Eleven cytidine analogues were selected for the anti
      viral test. Five of them belong to the family of the 2',3'-dideoxycytidine
      analogues, well known for their activity against human immunodeficiency virus
      (HIV). The others, all newly synthesized, were potential anti-viral and/or anti
      leukemic agents. None of the compounds under study had a toxic effect in both
      anti-viral assay systems up to a 300 microM concentration. Based on the
      cytopathic effects (CPE), the virus replication was completely inhibited by the
      five 2',3'-dideoxycytidine analogues at a concentration of 50 microM, whereas the
      others six newly synthesized compounds induced titre reductions of 4-5 log units.
      The effective concentration causing 50% reduction of CPE (EC50) was of 5 microM
      for the five 2',3'-dideooxycytidine analogues and for beta-L-XyloFc, whereas the
      value of 50 microM was found for the b-L-XyloC and the four 5-azacytidine
      compounds tested. All these data reveal a good correlation between inhibition of
      MVV replication by several nucleoside cytidine analogues and their reported anti
      HIV activity.

PMID- 11247043
TI  - Cross-reactive proteins among eight bovine mycoplasmas detected by monoclonal
      antibodies.
AB  - Whole cell proteins of eight bovine mycoplasmas (M. bovoculi, M. bovis, M.
      dispar, M. bovirhinis, M. arginini, M. verecundum, M. canadense, M. alkalescens)
      were separated by SDS-PAGE and transferred to nitrocellulose paper. Rabbit anti
      M. bovoculi serum was found to react with immunoblots of all mycoplasma species
      tested. These cross-reactive proteins were in the range of 35,000-100,000
      molecular weight. Monoclonal antibody MA25.5 developed against a M. bovoculi 94
      kDa surface protein cross-reacted with a band of 62 kDa from M. dispar and three
      bands of 89, 85 and 74 kDa from M. arginini only while MA18.13 that recognized a
      band of 57 kDa from M. bovoculi did not react with the other species. The role of
      MA25.5 monoclonal antibody in inhibiting the growth of M. bovoculi, M. dispar and
      M. arginini was tested using the metabolic-inhibition (MI) test. Monoclonal
      antibody MA25.5 inhibited the growth of M. bovoculi and also inhibited M. dispar
      growth but at lower MI titers, while it showed no effect on the growth of M.
      arginini.

PMID- 11247045
TI  - Isolation of virulent Rhodococcus equi from native Japanese horses.
AB  - R. equi was isolated from soil samples obtained from the environment of seven
      native Japanese horse breeds (Hokkaido, Kiso, Noma, Misaki, Tokara, Miyako and
      Yonaguni) and from fecal samples collected from three native horse breeds
      (Hokkaido, Kiso and Misaki). Virulent R. equi at various levels (ranging from 0.5
      to 12.9%) was isolated from the feces or soil environment of Hokkaido, Kiso and
      Misaki horses. Isolates were investigated both for the presence of 15- to 17-kDa
      antigens (virulence-associated protein antigens; VapA) by colony blotting, using
      the monoclonal antibody 10G5, and the gene of VapA by PCR. Plasmid DNAs extracted
      from positive isolates were digested with restriction endonucleases, and the
      digestion patterns of the plasmids of virulent isolates were divided into three
      types. Two of the three types (87-kb type II and 90-kb type I) had already been
      reported in Japanese isolates, and a new type (tentatively designated as 90-kb
      type II) had been found in isolates from Kiso horses. Six virulent R. equi
      isolates from the Hokkaido horses contained an 87-kb type II plasmid. Eight of 24
      isolates from the Kiso horses contained an 87-kb type II plasmid, and the
      remaining 16 contained a 90-kb type II (a new type) plasmid. Two isolates from
      the Misaki horses contained a 90-kb type I plasmid. These results demonstrate the
      geographic difference in the distribution of virulence plasmids in R. equi
      isolates among native Japanese horses.

PMID- 11247046
TI  - Simultaneous isolation of verotoxin-producing strains of Escherichia coli O128:H2
      and viruses in gastroenteritis outbreaks.
AB  - Three outbreaks of gastroenteritis from which the Verotoxin producing Escherichia
      coli serotype O128:H2 was isolated are reported. In addition Norwalk-like viruses
      were detected in patients from two of the outbreaks and astrovirus in the third
      outbreak. While it cannot be specifically determined which of these agents played
      the major role in these outbreaks, the findings suggest that the viral agents
      need to be considered in investigations of gastroenteritis outbreaks, regardless
      of whether bacterial enteropathogens have also been isolated. This study points
      to a strong need to investigate gastroenteritis outbreaks for both bacterial and
      viral agents and to review in detail the asymptomatic carriage rate of Verotoxin
      producing bacteria and gastroenteritis-associated viral agents; these areas of
      public health significance have been largely neglected.

PMID- 11247049
TI  - Analysis of potential antigens of protoscoleces isolated from pulmonary and
      hepatic hydatid cysts of Bubalus bubalis.
AB  - The aqueous soluble proteins of the protoscoleces of Echinococcus granulosus
      isolated from the pulmonary and hepatic hydatid cysts of Bubalus bubalis were
      partially purified on Sephadex G-200 column. The isolated fractions were tested
      for their antigenicity by immunodot using the sera collected from experimentally
      infected puppies during the prepatent period of infection. Six protein profiles
      (F1-F6) were recovered from both the isolates but the polypeptide recovery of
      each fraction of the two isolates were some what different, particularly protein
      concentration of F5 in the liver isolate was greater than the lung isolate.
      Contrary to this, the concentration of F1 polypeptides of the lung origin
      protoscoleces is greater as compared to that of the liver. In addition, some
      antigenic dissimilarity has also been observed in the two isolates. A weak IgG
      response against F1, F2 and F6 polypeptides was observed in the 4th day post
      infection (p.i.) sera. With the age of infection the response against these
      antigens increased as revealed by the intensity of the spot in immunodot
      analysis. Our studies show that the differences in the elution profile and
      antigenic profile of the lung and liver isolates, as revealed by gel filtration
      and immunodot analysis, might be either due to the influence of the microhabitat
      or these may be two different strains. Further studies are certainly required in
      this direction.

PMID- 11247047
TI  - Isolation of antibacteriologically active compounds from species of the Cottidae
      family.
AB  - Antibacteriologically active compounds were isolated from the skin of several
      species of the fish family Cottidae. Suitable samples were obtained from species
      living in the Pacific, lakes in North America and the Fenno-Scandinavian
      peninsula as well as the Baltic sea. The compounds isolated from the skin of
      Triglops quadricornis (fourhorn sculpin) from the Baltic sea were particularly
      studied. The activity was partially characterised by chemical and biochemical
      investigations and the susceptibility of several human and fish pathogens
      described. The substance or substance(s) are of a high molecular mass, resist
      proteolytic and glycolytic enzymes, are heat and pH sensitive and water soluble.

PMID- 11247048
TI  - Chlortetracycline modulates acute phase response of ex vivo perfused pig livers,
      and inhibits TNF-alpha secretion by isolated Kupffer cells.
AB  - Tetracyclines have been shown to have anti-inflammatory effects in addition to
      their antimicrobial action. We investigated the effects of in vivo administration
      of chlortetracycline (CTC) on ex vivo perfused pig livers. The retention and
      clearance of Salmonella choleraesuis, production of acute phase proteins C
      reactive protein (CRP), and haptoglobin (HPG) by whole livers were studied. The
      in vitro modulation by CTC of TNF-alpha secretion by pig Kupffer cells (KC) was
      also studied. Pigs were dosed orally with CTC for three days, and given
      injections of Salmonella LPS 24 h before removal of the liver. Salmonella
      retention and clearance by livers of pigs given CTC was lower than by control
      livers (p < 0.01 and p < 0.05, respectively). We demonstrated an increase of CRP
      and HPG by livers from control pigs after a three-hour perfusion while pigs from
      CTC pretreated pigs varied in this response. Further, CTC decreased the secretion
      of TNF-alpha by cultured KC incubated in vitro with LPS. Modulation of TNF-alpha
      production by CTC suggests a potential for attenuating the inflammatory response.
      However, this possible beneficial action of CTC was accompanied by a significant
      decline in the antimicrobial effect of the liver.

PMID- 11247050
TI  - Sleep in the blind mole rat Spalax ehrenbergi.
AB  - STUDY OBJECTIVES: The mole rat, Spalax ehrenbergi, is an interesting species for
      sleep because of its pronounced specialization to a fossorial life. These rodents
      spend most of their life-time underground, and are less exposed to many of the
      environmental stimuli and challenges that are common to non-fossorial rodents. A
      prominent adaptation is their blindness, which is due to an atrophy of the eyes.
      DESIGN: Continuous 24-h recordings of EEG, EMG and cortical temperature, and EEG
      spectral analysis were performed in six individuals caught in the wild and
      adapted to the laboratory for several months. SETTING: N/A. PATIENTS OR
      PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Total sleep time
      (52% of recording time) and the amount of REM sleep (8% of recording time) in
      these subterranean rodents are in the range of values found in the laboratory
      rat, mouse and hamster recorded under similar conditions. In contrast to these
      species, the polyphasic sleep-wakefulness distribution in mole rats was more
      distinct. A predominance of sleep in the dark period was only minor and not
      present in all individuals, which resembles sleep in the guinea pig. As in all
      other mammals investigated, the daily time course of EEG slow-wave activity (SWA)
      in nonREM sleep closely followed the polyphasic sleep-wake pattern and the light
      dark preference. The transitions from non REM sleep to REM sleep were
      characterized, as in other rodents, by a gradual increase in EEG activity in the
      theta and sigma frequency bands before the transition. However, the power surge
      in these frequencies massively exceeded that found in other rodents. This feature
      may be related to adaptations of the brain to the requirements of the
      subterranean habitat. CONCLUSIONS: It is remarkable that large ecological
      differences between species within the same order have relatively small effects
      on many sleep features. The time course of SWA confirmed its predictability on
      the basis of the previous sleep-wake history.

PMID- 11247051
TI  - The effects of ondansetron on sleep-disordered breathing in the English bulldog.
AB  - Serotonin and serotoninergic drugs have significant effects on respiration, at
      many sites throughout the nervous system, and serotonin has been implicated in
      the pathogenesis of obstructive sleep apnea. Thus, understanding the
      serotoninergic mechanisms underlying respiratory control may help discover novel
      pharmacotherapies for sleep-disordered breathing. Ondansetron, a serotonin (5-HT)
      antagonist selective for the 5-HT3 receptor subtype has recently been shown to
      suppress sleep-related central apneas in rats, particularly in rapid-eye-movement
      (REM) sleep. To evaluate the potential of ondansetron in the treatment of
      obstructive sleep-disordered breathing, we have performed randomized trials of
      two doses of ondansetron (20 and 40 mg orally) and placebo (4 studies for each of
      the 3 conditions) in our animal model of obstructive sleep apnea, the English
      Bulldog. Ondansetron significantly reduced the respiratory disturbance index
      (RDI) in REM sleep from 24.15+/-4.85 events/hour at placebo to 11.01+/-1.56
      events/hour with high dose treatment, n=4, p<0.05. In contrast, the effects of
      drug on the RDI in non-rapid-eye-movement (NREM) sleep (5.23+/-1.30 events/hour,
      placebo; 4.31+/-1.36, with 20 mg ondansetron and 2.89+/-1.30 with 40 mg
      ondansetron, n=4) were not significant. Ondansetron, however, had no effect on
      either sleep efficiency or sleep architecture, and there were no effects on
      either oxyhemoglobin saturation nadirs or on the sleep time with saturations
      <90%. Although a trend towards reduction in the latter measure of oxygenation was
      seen at the higher dose of ondansetron. These data suggest a therapeutic
      potential for ondansetron in obstructive sleep-disordered breathing, particularly
      REM sleep apnea.

PMID- 11247052
TI  - Memory sources associated with REM and NREM dream reports throughout the night: a
      new look at the data.
AB  - The data from three previously published studies on the memory sources of dreams,
      representing nine different moments of awakening throughout the night, are re
      examined. In the original studies, elicited reports were recorded and segmented
      online into thematic units. The segmented reports were played back to Ss who were
      asked to identify memory sources or to associate to each segment. Memory sources
      were classified as episodic, semantic, or abstract self-references. In the meta
      analysis and re-analyses reported here, the mean percentages of episodic memory
      sources are plotted separately for NREM and REM awakenings throughout the night.
      Within stages, neither NREM nor REM mean percentages differ significantly from
      each other, whereas between stages the mean percentage of episodic memory sources
      is significantly greater for NREM than for REM. Even when the correlation between
      report length and sleep stage is controlled by computing memory source density,
      the stage effect throughout the night persists for episodic memory sources. The
      relatively flat episodic memory curves for both NREM and REM indicate a rather
      constant recruitment of episodic memory sources throughout the night. No stage
      effect was found for strictly semantic memory sources. When semantic memory was
      defined generically, however, to include all non-spatio-temporal, "unmarked,"
      information of self as well as of world, significantly more generic semantic
      memory sources derived from REM than from NREM reports, though not when corrected
      for the length of dream reports.

PMID- 11247054
TI  - Exogenous melatonin in periodic limb movement disorder: an open clinical trial
      and a hypothesis.
AB  - STUDY OBJECTIVES: The etiology of Periodic Limb Movement Disorder (PLMD) as well
      as the precise role of melatonin in human physiology remains poorly understood.
      Inspired by a single case observation we performed the presented study in order
      to obtain first evidence for the hypothesis that exogenous melatonin would
      decrease PLM's and thereby improves symptoms of PLMD patients. DESIGN: N/A.
      SETTING: N/A. PATIENTS/PARTICIPANTS: Nine patients with first time diagnosis of
      PLMD without RLS were treated over a six-week period with 3 mg melatonin, taken
      between 10 and 11 p.m. INTERVENTIONS: N/A. RESULTS: Melatonin improved well-being
      in 7 of the 9 patients. Polysomnography, performed prior and at the end of
      melatonin treatment, demonstrated a significant reduction of investigated
      movement parameters, such as PLMs, PLM index, PLMs with arousals and PLM-arousal
      index. Actigraphy, measured over 14 nights prior and during the last 14 days of
      melatonin treatment, showed a significant reduction in movement rate and minutes
      with movements during Time in Bed. CONCLUSIONS: The temporal distribution of
      PLMs, as well as the coupling of PLMs with the phase position of circadian
      temperature curve, suggest an involvement of the circadian timing system in the
      pathophysiology of PLMD. Locomotor activity in animals clearly exhibits a
      circadian pattern and can be strongly influenced by exogenous melatonin. Results
      suggest a chronobiotic effect of exogenous melatonin in PLMD. More specifically,
      we hypothesize that the mode of action of melatonin in the presented PLMD
      patients might have been an increase of output-amplitude of the circadian timing
      system, thereby enhancing the circadian rhythmicity of locomotor activity with a
      reduction of sleep motor activity.

PMID- 11247053
TI  - Brain-mind states: I. Longitudinal field study of sleep/wake factors influencing
      mentation report length.
AB  - STUDY OBJECTIVES: To collect and analyze reports of mental activity across
      sleep/wake states. DESIGN: Mentation reports were collected in a longitudinal
      design by combining our Nightcap sleep monitor with daytime experience sampling
      techniques. Reports were collected over 14 days and nights from active and quiet
      wake, after instrumental awakenings at sleep onset, and after both spontaneous
      and instrumental awakenings from REM and NREM sleep. SETTING: All reports were
      collected in the normal home, work and school environments of the subjects.
      PARTICIPANTS: Subjects included 8 male and 8 female undergraduate students (19-26
      years of age). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: A total of 1,748
      reports, averaging 109 per subject, were collected from active wake across the
      day (n=894), from quiet wake in the pre-sleep onset period (n=58), from sleep
      onset (n=280), and from later REM (n=269) and nonREM (n=247) awakenings. Median
      report lengths varied more than 2-fold, in the order REM > active wake > quiet
      wake > NREM = sleep onset. The extended protocol allowed many novel comparisons
      between conditions. In addition, while spontaneous REM reports were longer than
      those from forced awakenings, the difference was explained by the time within the
      REM period at which the awakenings occurred. Finally, intersubject differences in
      REM report lengths were correlated with similar differences in waking report
      lengths. CONCLUSIONS: The use of the Nightcap sleep monitoring system along with
      waking experience sampling permits a more complete sampling and analysis of
      mental activity across the sleep/wake cycle than has been previously possible.

PMID- 11247055
TI  - The association of upper airway resistance with periodic limb movements.
AB  - STUDY OBJECTIVES: We hypothesized that the upper airway resistance syndrome
      (UARS), the component event being a respiratory effort related arousal (RERA),
      and periodic limb movements in sleep (PLMS), the component event being
      repetitive, stereotyped extremity movements occurring in a periodic fashion, were
      associated in certain patients. DESIGN: Invasive polysomnography using Pes and
      full facemask pneumotachography was used to identify RERA's in patients. Periodic
      limb movements (PLM) were scored according to standard criteria and as associated
      with RERA if the movement occurred between the Pes nadir and the onset of the
      arousal. SETTING: A university hospital Sleep Disorders Laboratory. PARTICIPANTS:
      Patients consecutively diagnosed with PLMS in our sleep disorders laboratory over
      a 1 year period. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Fourteen of
      twenty patients demonstrated UARS in addition to PLMS (70%). In those 14, 63% of
      RERAs were associated with a PLM (mean = 51.7 + 36.2 PLM/RERAs per study vs 5.6 +
      6.3 PLM/RERAs per study if the association were random). Patients with UARS had
      more arousals with their PLMs (P = 0.0006). CONCLUSIONS: An association exists
      between PLMS and UARS on both a group level and an event level. A high percentage
      of PLM with arousals correlated with breathing events due to increased effort in
      UARS; this may be of clinical utility in the management of PLMS patients.

PMID- 11247056
TI  - Effect of total sleep deprivation on the dimensional complexity of the waking
      EEG.
AB  - STUDY OBJECTIVES: Sleep deprivation can affect the waking EEG that may reflect
      information processing of the brain. We examined the effect of total sleep
      deprivation (TSD) on nonlinear dynamics of the waking EEG. DESIGN: Paired-group
      design. SETTING: A sleep disorders laboratory in a hospital. PARTICIPANTS: Twenty
      healthy male volunteers. INTERVENTIONS: Waking EEG data were recorded from
      subjects with eyes closed after (a) an 8-hour night's sleep and (b) TSD for 24
      hours. The dimensional complexity (D2), as a nonlinear measure of complexity, of
      the EEG after a full night sleep were compared with those of the EEG after TSD.
      MEASUREMENTS AND RESULTS: The sleep-deprived states had lower D2 values at three
      channels (P4, O2, and C3) than normal states. CONCLUSIONS: TSD results in the
      decrease of complexity in the brain, which may imply sub-optimal information
      processing of the cerebral cortex. We suggest that the investigation of the
      relation between nonlinear dynamics of the waking EEG induced by TSD and
      cognitive performance may offer fruitful clues for understanding the role of
      sleep and the effects of sleep deprivation on brain function.

PMID- 11247057
TI  - The contributing role of sleepiness in highway vehicle accidents.
AB  - STUDY OBJECTIVE: To evaluate the contributing role of sleepiness in Italian
      highway vehicle accidents during the time span 1993-1997. DESIGN: We analyzed
      separately the hourly distribution of accidents ascribed by police officers
      univocally to sleepiness and the rest. PATIENTS: N/A. INTERVENTIONS: N/A.
      MEASUREMENTS: Using a polynomial regression, we evaluated the relation between
      accidents (whether sleep-ascribed or not) and sleepiness as derived from a 24
      hour sleep propensity curve. The relation between sleep-influenced and non-sleep
      influenced accidents was analysed using a linear regression. RESULTS: The rate of
      non-sleep ascribed accidents is closely related with sleep propensity and bears a
      strong similarity with the pattern of sleep-ascribed accidents. A close
      relationship between the curves of non-sleep ascribed accidents and sleep
      ascribed accidents is confirmed. The regression coefficient, which can be seen as
      the ratio between the quota of accidents that can be considered as sleep affected
      and those actually ascribed to sleepiness, results in a value of 5.83.
      Considering that the rate of sleep ascribed accidents is 3.2%, we can calculate
      the quota of sleep influenced accidents out of those not officially ascribed to
      sleepiness as 18.7% reaching an estimate of accidents related in some way to
      sleepiness equal to 21.9%. CONCLUSIONS: Our indirect estimate of sleep influenced
      accidents approaches data reported by other European countries and highlights the
      importance of sleepiness as a direct and/or contributing factor in vehicle
      accident rates.

PMID- 11247058
TI  - Cardiorespiratory and autonomic interactions during snoring related resistive
      breathing.
AB  - STUDY OBJECTIVES: We hypothesized that blood pressure (BP) is less during snoring
      as compared to periods of non-snoring in non-apneic individuals. Furthermore, we
      hypothesized that this reduction may be accompanied by a simultaneous decrease in
      sympathetic (SNSA) and parasympathetic (PNSA) nervous system activity and an
      increase in heart rate (HR). DESIGN: N/A. SETTING: N/A. PATIENTS OR PARTICIPANTS:
      N/A. MEASUREMENTS: The variables mentioned above in addition to breathing
      frequency were measured in 9 subjects during NREM sleep. In addition, the lowest
      systolic (SBP) and diastolic blood pressure (DBP) during inspiration and the
      highest SBP and DBP during expiration was determined breath-by-breath from
      segments selected from each NREM cycle. Heart rate variability was used as a
      marker of autonomic nervous system activity. RESULTS: Our results showed that BP
      during snoring decreased compared to non-snoring and the breath-by-breath BP
      analysis suggested that this difference may have been mediated by changes in
      intrathoracic pressure. In conjunction with the decrease in BP, SNSA decreased
      and HR increased however PNSA remained constant. Thus, a decrease in PNSA was
      likely not the primary mechanism responsible for the HR response. CONCLUSIONS: We
      conclude that BP responses and SNSA during snoring are similar to that reported
      previously in non-snoring individuals. However, the causal mechanisms maybe
      different and manifested in other measures such as HR. Thus, nocturnal
      cardiovascular and autonomic function maybe uniquely different in non-apneic
      snoring individuals.

PMID- 11247059
TI  - Increase in bilirubin levels of patients with obstructive sleep apnea in the
      morning--a possible explanation of induced heme oxygenase-1.
AB  - STUDY OBJECTIVES: In the absence of heme oxygenase-1 (HO-1), which catalyzes the
      oxidation of heme to generate carbon monoxide and indirect bilirubin, hypoxia
      induces severe right ventricular dilation and infarction. Despite severe
      hypoxemia during sleep, patients with obstructive sleep apnea-hypopnea syndrome
      (OSAHS) rarely die during sleep. We hypothesized that apnea-related hypoxemia
      would induce HO-1 and increase bilirubin levels in the morning in OSAHS patients.
      Therefore, bilirubin levels in OSAHS patients were analyzed before and after
      nasal continuous positive airway pressure (nCPAP) therapy. DESIGN: Bilirubin
      levels in the afternoon before sleep and in the morning immediately after sleep
      were determined before and after nCPAP treatment. SETTING: University Hospital in
      Kyoto, Japan. PATIENTS: The subjects were 22 patients with OSAHS (mean (SEM)
      apnea and hypopnea index of 60 (5)) who were treated with nCPAP and 13 controls.
      INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Before nCPAP treatment, total after
      sleep bilirubin level was significantly higher than the pre-sleep level
      (p<0.0001). The difference between the serum indirect bilirubin levels in the
      morning versus in the previous afternoon [D-(M-A)-IB] decreased significantly
      with nCPAP treatment (p<0.01). The magnitude of decrease in D-(M-A)-IB after
      nCPAP treatment correlated significantly with changes in the percent time spent
      with arterial O2 saturation below 90% (r=0.44; p=0.04) and 85% (r=0.49; p=0.02),
      respectively, during sleep after nCPAP treatment. CONCLUSIONS: The increase in
      bilirubin level by HO-1 might protect OSAHS patients from disorders related to
      hypoxemia.

PMID- 11247060
TI  - Development of a brief, self-administered instrument for assessing sleep
      knowledge in medical education: "the ASKME Survey".
AB  - STUDY OBJECTIVES: This report describes the construction and validation of a
      brief self-administered scale to assess sleep knowledge in medical education
      ("ASKME Survey"). Few measures of this type have been developed previously; none
      have been validated or widely adopted. The current instrument was designed as a
      standardized assessment measure for use in medical education in sleep. DESIGN:
      Instrument was developed in four phases: initial item selection, expert panel
      review, reliability and construct validity assessment, and final item selection.
      Content validity was assessed in six general domains: basic sleep principles;
      circadian sleep/wake regulation; normal sleep architecture; sleep disorders;
      effects of drugs and alcohol on sleep; and sleep in medical disorders. SETTING:
      N/A. PARTICIPANTS: Medical students at Robert Wood Johnson Medical School (RWJMS)
      and University of Kentucky College of Medicine; students in clinical psychology,
      nursing and other health-related professions at Rutgers University; school nurses
      at Texas Christian University; practicing physicians; accredited sleep
      specialists. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Individual item
      analysis of 30-item survey demonstrated a high degree of discriminant validity.
      Internal consistency for test items was relatively high (KR-20=0.89). Overall
      mean percentage correct was highest for accredited sleep specialists (85.3%+/
      10.8%) and lowest for school nurses (53.1%+/-13.7%). Significant group
      differences were observed across all question categories (p < 0.0001). Medical
      students scored significantly higher than the nurses on questions related to
      sleep architecture (59.5% vs. 42.5%) and narcolepsy (36.4% vs. 21.3%).
      CONCLUSIONS: "ASKME" demonstrates a high degree of internal consistency and
      reliability among survey items. It discriminates between samples with varied
      levels of education, experience, and specialty training. The survey is currently
      available via the American Academy of Sleep Medicine website
      (http://www.aasmnet.org).

PMID- 11247061
TI  - [Minimally invasive laparoscopic cholecystectomy - analgesia and pulmonary
      function].
AB  - This is a report on 27 patients subjected to cholecystectomy for calculous
      cholecystitis through minilaparotomy. In 21 of them minicholecystectomy is
      performed under conditions of intubation inhalatory anesthesia. In the remainder
      (6 cases) intraoperative epidural analgesia is approbated, proceed-in during the
      short postoperative period. The laboratory and functional parameters, having an
      essential practical bearing on analgesia and pulmonary function, are monitored
      both intra- and postoperatively.

PMID- 11247062
TI  - [The role of laparoscopy and laparoscopic ultrasonography in the diagnosis and
      differential diagnosis of nodular hepatocellular lesions].
AB  - The diagnostic relevance of laparoscopy (LS) and laparoscopic echography (LE) in
      nodular hepatocellular lesions is studied. LS is done using a R. Wolf
      laparoscope, and LE--with a 7.5 MHz linear transducer, obtained from the Aloka
      Company. A total of 250 patients presenting 288 nodular hepatocellular lesions
      are investigated over 15 years (1983-1998), including: focal nodular hyperplasia
      (FNH)--1, nodular regenerative hyperplasia (NRH)--1, hepatocellular adenoma (HCA)
      -1, adenomatous hyperplasia (AH)--38, hepatocellular carcinoma (HCC)--58, Budd
      Chiari syndrome--2, primary sclerosing cholangitis (PSCh)--2, and cirrhosis of
      liver--185. The lesions are distributed according to the updated classification
      of the International Working Party, published in 1995. In addition to the latter,
      a case of cholangiocellular adenoma undergoing malignant degeneration and a case
      presenting carcinoma, giving rise to differential diagnostic difficulties are
      also described. Some of the aforementioned diseases are reported for the first
      time in the Bulgarian literature. Emphasis is laid on the practicability of
      combining endoscopic with imaging diagnostics, attributable to laparoscopic
      echography and to the advantages of echolaparoscopic biopsy. Almost half of the
      foci (46.1%) are morphologically verified. The aim of cytological assessment is
      to establish the malignant character of the lesion, first and foremost, while the
      histological finding is essential for making a correct diagnosis.

PMID- 11247063
TI  - [Breast carcinoma - a challenge faced by surgeons].
AB  - We are representing results of some projects of Oncology Centre in Pleven about
      some problems in breast cancer, like: local screening program for early
      diagnostic of the disease and how to choose axillary dissection and axillary
      staging by sentinel lymphadenectomy and reconstructive surgery after mastectomy.

PMID- 11247064
TI  - [Factors influencing the cosmetic outcome in early breast cancer patients
      following salvage surgery and radioisotope teletherapy].
AB  - It is the purpose of the report to analyze the factors exerting effect on the
      cosmetic outcome in breast cancer patients (I-II clinical stage), following organ
      salvaging operation in conjunction with telegammatherapy. Assessment of the
      cosmetic results in 100 female patients with early mammary gland cancer is done 5
      years after complex treatment (conservative surgery, postoperative radiotherapy,
      and chemo- and/or hormonotherapy when indicated). The influence of eight factors
      on the cosmetic outcome attained is evaluated through correlative statistical
      analysis, namely: breast size, scope of the surgical intervention, number of
      lymph nodes dissected, type of operative cicatrix, dose exposure of the entire
      mamma, homogeneity of radiation dose distribution in tre entire mammary gland,
      dose exposure of the tumor bed and adjuvant therapy. The analysis performed
      points to the important practical implications of three of the factors: size of
      operative intervention (axillary dissection range), breast volume and homogeneity
      of the irradiation dose in the entire breast.

PMID- 11247065
TI  - [Salvage therapy in early stage breast carcinoma. II. Radiotherapy - an essential
      and necessary component in a new therapeutic approach].
AB  - A concerving surgery in the treatment of early breast carcinoma definitely need
      to be followed by radiotherapy to control local recurrence of disease. However,
      the rate of local recurrence is lowest with quadrantectomy versus tumotectomy,
      while the reverse is true as regards cosmetic results. Progressive integration of
      the different therapeutic approaches is expected to characterise the coming
      years, to combine safety with good esthetic results.

PMID- 11247066
TI  - [The role of urinary tract infections in burn patients].
AB  - Patients with burns are predisposed to a variety of infectious complications,
      urinary tract infections inclusive. It is the aim of the study to assay the
      incidence rate, etiology and antibacterial sensitivity of the leading pathogens
      causing bacteriuria in burnt patients, and compare them with the respective
      characteristics of the pathogens causing wound infection in the same contingent
      of patients, and urinary tract infection in uro-nephrological patients. Over a
      five-year period, a total of 2452 urines and 4236 wound exudates from 963
      patients with burns, and 8800 urines from 2908 uro-nephrological patients are
      studied. In 35.4 per cent of patients positivation of 29.2 per cent of the urines
      being examined is noted. The major causing agents producing bacteriuria in burns-
      E. coli (19.2%) and Proteus mirabilis (13.9%)--are similar to the ones found in
      uro-nephrological patients, and differ from the causing agents of wound infection
      (the isolates concur in 16.7 per cent of the cases only). The inference is
      reached that strict monitoring of burnt patients is absolutely necessary because
      they run a high risk of urinary infection development, most frequently caused by
      multiresistant hospital strains, worsening the prognosis of either of the
      conditions. Monotherapy prescription with broad-spectrum antibacterial agents,
      based on the sensitivity of isolates in vitro, is strongly recommended.

PMID- 11247068
TI  - [Bilateral endometriosis of the ureters].

PMID- 11247067
TI  - [Treatment of benign prostatic hyperplasia with tamsulosin].
AB  - The past few decades mark a rejuvenation of the contingent of benign prostate
      hyperplasia (BPH) patients. The condition affects mainly the active age in men,
      with the substantial financial burden of treatment leading to a surge of interest
      in the disease. The hazards of postoperative complications development constrain
      modern urologists to seek for new, safer and more effective methods of
      conservative management. The task undertaken is to assay the effect of
      application and possible side phenomena of Tamsulosin treatment in BPH patients,
      administered at dose 0.4 mg a single time on a daily basis over 12 to 24 weeks. A
      nationwide multicenter, parallel, randomized study is conducted in seven
      urological clinical units throughout the country, covering a one year period. For
      the purpose a total of 310 men, aged 52 to 68 years, presenting moderately
      expressed BPH symptomatology are investigated. IPSS improvement is documented in
      229 patients (74%), and a significant MUD improvement is observed in 115 patients
      (37%), with the residual urine quantity decreasing significantly in 108 patients
      (35%). In conclusion, it is believed that Tamsulosin administration as a
      superselective alpha-1-A adrenoblocker is one of major achievements in the
      conservative therapeutic approach to prostate adenoma.

PMID- 11247069
TI  - [Urothelial tumors versus "endemic" nephropathy - myth or reality?].
AB  - Malignant tumors of the renal pelvis account for over 78 per cent of all
      malignant tumors of the kidney, and less than 1 per cent of all urogenital
      neoplasms. At the time of diagnosing, almost one third of these patients present
      with tumor of the ipsilateral ureter or bladder, and 40-50 per cent have ureteral
      tumor located elsewhere (D. Crawford, S. Das, 1990). After World War Two, the
      frequency of publications on cases of primary tumors of the pelvis show a
      noticeable increase, e.g. in Yugoslavia and Bulgaria the ratio of parenchymatous
      renal tumors to those of the renal pelvis is conspicuously altered. S. Petcovic
      (1970) and S. Lambrev (1972) attribute this fact to the existence of endemic
      "nephropathy" foci. It is the purpose of this work to analyze twenty-nine
      patients presenting carcinoma of the upper urinary ways, studied in the Chair of
      Urology in the period 1991 through 1997. Of them only four come from "endemic"
      regions. Over the period 1972-1975, fifty-nine patients with the same condition
      undergo treatment in the aforementioned Chair. It is worth noting that patients
      from the so-called "endemic" regions lack the typical signs of "endemic"
      nephropathy. The assumption is warranted that "endemic" nephropathy is a still
      not well enough clarified nosological entity, bearing resemblance to
      contamination with radioactive elements with a "boom" during the half-life period
      gradually subsiding.

PMID- 11247070
TI  - [Nodular regenerative hepatic hyperplasia in the differential diagnosis of focal
      hepatic lesions. Case report and review of the literature].

PMID- 11247071
TI  - [Clinical assessment in patients presenting brain metastases].
AB  - Over the period January 1988 to January 1998, in the clinic of emergency
      neurology and neurosurgery of the University Hospital "Queen Giovanna"--Sofia a
      total of 348 patients with brain tumors are hospitalized. Of them 329 cases are
      subjected to operation, and in 19 no surgery is undertaken. Forty-four patients
      with metastatic brain tumors are operated, and in 14 no operation is done. Of
      those operated 25 (56.8%) are men, and 19 (43.2%)--women. The mean age of male
      patients is 53.9 years, and of female patients--54.4 years. In 35 cases the
      metastases are supratentorially situated, and in eight--subtentorially (a female
      patient has both supra- and subtentorial metastases). Reoperation is performed in
      three patients, and one dies after the operation. In 13 cases (29.5%) the primary
      focus of lesion is known prior to operation. Of all patients included in the
      series 6 present pulmonary carcinoma (46%), 5--melanoma (30.8%), 2--breast
      carcinoma (15.4%), and one--carcinoma of the gastrointestinal tract (7.8%).

PMID- 11247072
TI  - [A modified variant biliary passage restoration in iatrogenic lesions].

PMID- 11247073
TI  - [Two-year experience with the jet dissector "Parenchymotome 01" in clinical
      practice].

PMID- 11247075
TI  - [Reconstructive surgery of the gastrointestinal tract].

PMID- 11247074
TI  - [Liver resection in a state of normothermic ischemia].
AB  - Thirty-three patients undergoing liver resection in a state of normothermic
      ischemia are described: portal clamping is done in 25 cases at mean duration 41
      +/- 8 min, and vascular exclusion of liver--10 cases at mean duration 44 +/- 12
      min. This is a procedure accounting for a substantial reduction of intraoperative
      hemorrhages. In 17 patients hemotransfusion proves unnecessary, while in the
      remainder the amount of blood transfused averaged 1500 +/- 950 ml.

PMID- 11247077
TI  - [Restitution in colorectal carcinoma patients after Hartmann's operation].

PMID- 11247076
TI  - [Complications of colorectal carcinoma in advanced and old age].

PMID- 11247079
TI  - [Microlaparocholecystectomy].

PMID- 11247078
TI  - [Surgical treatment of insulinomas with observations on six cases in one year].
AB  - Insulinomas are among the endocrine pancreatic tumors most commonly met with.
      Regardless of their small proportion compared to other tumors of the digestive
      system, they give rise to pressing surgical problems on account of a number of
      reasons, namely: 1) early clinical diagnosis and undertaking opportune operative
      management in those presenting benign neoplasms, even in oligosymptomatic cases,
      2) exact topical preoperative diagnosis using echography, CAT, MRI, angiography
      and the like; 3) intraoperative identification of the tumor/tumors in the event
      of multiple involvement, and choice of the most adequate operative approach, 4)
      intra- and postoperative monitoring of the blood sugar levels and appropriate
      insulin therapy prescription. Over the period Jan/Oct 1997, six patients
      presenting clinical, laboratory and instrumental evidence of insulinomas are
      subjected to operation in Department of General and Operative Surgery of the
      Medical University-Sofia. The basic principles with a reference to preoperative
      topical diagnosis and surgical tactics adopted, as well as postoperative care and
      monitoring of hyperglycemia developing as the result of surgery, are thoroughly
      discussed. Good immediate and long-term postoperative results are recorded in all
      six patients.

PMID- 11247081
TI  - [Diffuse purulent peritonitis in advanced and old age patients].

PMID- 11247080
TI  - [Surgical treatment of small intestinal obstruction in advanced and old age].

PMID- 11247082
TI  - [Ten-years' experience in the treatment of perforated gastric and duodenal
      ulcers].

PMID- 11247083
TI  - [Complications of cholelithiasis in advanced and old age patients under emergency
      conditions].

PMID- 11247084
TI  - [Surgical treatments in recurrent Graves' disease].
AB  - Seventy-six patients with clinical diagnosis Graves' disease, reoperated in the
      Clinic of Endocrine Surgery over the period 1985 through 1996, are analyzed.
      Distribution by gender and age: 3 men with mean age 55.33 y (range 49-60), and 73
      women at mean age 39.67 years (range 19-69). The scope of secondary operation
      includes: thyroidectomy--3 cases, subtotal thyroid resection--55, lobectomy with
      contralateral subtotal resection--2, and unilateral predominantly subtotal
      resection--16 cases. It is the purpose of the study to assay the underlying
      causes of surgical relapse in Graves' disease, its relationship to the radicalism
      of the intervention, thyrostatic therapy duration, and early and late
      postoperative complications associated with its removal. In 16 cases (21.05%)
      secondary operative intervention is done against the background of enhanced
      production of thyroid hormones. A short 3 to 6-month thyrostatic course precedes
      the reoperation in eleven patients (14.47%). Unilateral thyroid resection is
      resorted to in 16 patients (21.05%). Postoperative hypothyroidism is observed in
      6 cases (7.89%). A relapse of Graves' disease after reoperation is noted in 3
      instances (3.94%). Six patients of the series reviewed (7.89%) develop
      postoperative hypoparathyroidism: transitory in four (5.26%) and permanent in two
      (2.63%). In the early postoperative period, paresis of n recurrents (n laryngeus
      inferior) develops in 2 patients (2.63%): left- and rightside, one each
      respectively. In terms of morphological patterns, the ensuing relapses after
      surgery in Graves' disease patients portray the initial pathological process:
      some cases show a tendency of nodular adenomatous hyperplasia development,
      sporadic cases form follicular adenomas, and in 14 cases (18.42%) lymphoid
      infiltrates predominate with a tendency to be converted into Hashimoto's
      thyroiditis. The presence of enhanced proliferative response induced by a variety
      of factors, therapeutic ones inclusive, is the basic morphological factor of the
      recurrent conditions described.

PMID- 11247085
TI  - [Application of skin expander in the operative treatment of extensive hemangiomas
      and lymphangiomas in early childhood]].

PMID- 11247086
TI  - [Surgery in advanced and old-age diseases].

PMID- 11247087
TI  - [Conservative surgery in renal carcinoma in case of contralateral kidney
      involvement]].
AB  - A serious problem faced in renal carcinoma treatment are patients presenting
      bilateral tumor, or those with virtually one kidney. Over a 2-year period, in the
      Department of Urology three patients are subjected to operation--one with
      bilateral renal carcinoma, one with dysfunction of the contralateral kidney, and
      one with a large cyst of the contralateral kidney. In the patient presenting
      bilateral tumor, nephrectomy on one side and partial resection on the other are
      performed, and in the remainder two--enucleation of the neoplasm. The patient
      with contralateral loss of renal function is subjected to ipsilateral operation
      for calculosis before the intervention with ensuing lithotripsy--three times.
      Within a year of the operation the same patient undergoes operation for
      ipsilateral pyonephrosis. At the time of study, all three patients are in a good
      general condition with values of the residual nitrogen bodies within normal
      limits.

PMID- 11247088
TI  - [One-stage surgical techniques in various hypospadias locations].
AB  - Hypospadias is a common developmental anomaly in the male (8.2@1000). Over the
      last twenty years, one-stage operative techniques for the correction of this
      anomaly have been widely adopted. Two-stage procedures remain a method of choice
      in strictly selected cases only. In the period 1992 through 1997, thirty patients
      aged 2-19 years presenting different locations of hypospadias are picked out in
      the Department of Urology-"Alexandrovska" University Hospital. The following
      operative techniques are used: Magpai-Duplay-Fierlit, Flip-Flap, Duket De-Sey,
      Huchson, Ducet-Duplay, Ducet-Flip-Flap. The complications resulting are
      operatively closed within 3 months of plastic repair, and in case of stenosis of
      the meatus meatoplasty is done. The good results of one-stage operations in
      hypospadias, irrespective of the location, justify their adoption as a plastic
      repair method of choice.

PMID- 11247089
TI  - [Echinococcus cyst perforation into the colon].

PMID- 11247090
TI  - [Acute onset of abdominal complications in thoracic sarcoidosis patients].

PMID- 11247091
TI  - [M. Sternalis - anomaly associated with diagnostic problems in breast cancer].

PMID- 11247092
TI  - [An instrument for reconstruction and plastic surgery of the terminal
      choledochus].

PMID- 11247093
TI  - Longitudinal follow-up of naturalistic treatment outcome in patients with
      trichotillomania.
AB  - BACKGROUND: Little is known about the longitudinal course of treatment outcome in
      patients with trichotillomania. The authors conducted a second follow-up
      assessment on a cohort of hair pullers previously studied. METHOD: Forty-four
      subjects completed a hair-pulling questionnaire and paper-and-pencil measures of
      hair-pulling severity and impact, psychosocial functioning, depression, anxiety,
      and self-esteem. Mean time elapsed between the first and second follow-up
      assessment was 2.5 years (index evaluation to first follow-up = 3.5 years).
      RESULTS: Twenty-seven subjects (61.4%) had active treatment since the first
      follow-up. No significant changes in hair pulling, depression, anxiety, or
      psychosocial functioning were reported from first to second follow-up. Self
      esteem scores significantly worsened during this period (p = .000). A trend
      toward worsening also existed for psychosocial impact scores. Comparison of
      scores at index evaluation with second follow-up still showed significant
      improvement over time for hair pulling (p = .001) but significant worsening in
      self-esteem (p = .000). Treatment and responder status were unrelated to clinical
      functioning, with the exception of depression and psychosocial impact.
      CONCLUSION: Although hair pullers exhibit initial improvement with treatment,
      scale scores plateau or worsen by second follow-up. Significant worsening in self
      esteem at second follow-up may be related to the absence of further improvements
      in hair-pulling severity. Future research should focus on the interrelationships
      among self-esteem, depression, and hair pulling during treatment for this
      disorder.

PMID- 11247094
TI  - Electroconvulsive therapy and cardiovascular complications in patients taking
      trazodone for insomnia.
AB  - BACKGROUND: Trazodone has been used widely to treat insomnia in depressed
      patients. When used in combination with electroconvulsive therapy (ECT),
      trazodone has been suspected to cause cardiovascular side effects. METHOD: A
      retrospective study was done of 100 patients who received ECT with concurrent
      trazodone. One patient was excluded because permission to review the patient's
      records had not been given. The remaining 99 patients were matched with control
      ECT patients. RESULTS: No statistically significant between-group differences
      were identified in cardiovascular side effects, although a trend toward more
      orthostatic hypotension was observed in patients taking trazodone. CONCLUSION:
      Administering low-dose trazodone for insomnia in conjunction with ECT does not
      appear to increase cardiovascular complications. The true incidence of adverse
      cardiac events was not higher than 3.66% at a 95% confidence level.

PMID- 11247095
TI  - Serum fluvoxamine levels in breastfed infants.
AB  - BACKGROUND: Between 10% and 15% of new mothers will experience an episode of
      postpartum depression. Although antidepressants are effective agents for the
      treatment of postpartum depression, minimal data are available to support their
      safety in infants of breastfeeding mothers. METHOD: In this article, we present 2
      cases of nursing mother-infant pairs in which the mother was treated with
      fluvoxamine and in which infant serum fluvoxamine levels were obtained. Both
      mothers began the fluvoxamine treatment postpartum, and serum levels were
      obtained from mothers and infants after a minimum of 7 days on a stable maternal
      dose. One level was obtained from the infant in case 1, and 2 levels were
      obtained from the infant in case 2. RESULTS: Each of the infant serum fluvoxamine
      levels obtained was too low to quantify (at a limit of detection of 2.5 ng/mL).
      Neither of the infants experienced adverse events related to the mother's
      treatment with fluvoxamine. Each of the infants is reportedly healthy 2 to 3
      years after the exposure. CONCLUSION: While these results are encouraging, they
      are limited and cannot be generalized to all cases of infants exposed to
      fluvoxamine. Additional mother-infant serum fluvoxamine levels and infant
      behavioral observations will facilitate the risk-benefit decision-making process
      for women who choose to breast-feed while taking fluvoxamine.

PMID- 11247096
TI  - Weight gain with risperidone among patients with mental retardation: effect of
      calorie restriction.
AB  - BACKGROUND: The atypical antipsychotics cause weight gain, which is poorly
      understood in terms of its mechanism and treatment. A usual recommendation for
      treatment of antipsychotic-induced weight gain includes calorie restriction and
      exercise. The authors describe their recent clinical experience with calorie
      restriction in adults with mental retardation treated with risperidone. METHOD: A
      retrospective chart review was performed on the records of 50 adult patients with
      mental retardation treated with risperidone while residing at a habilitation
      center. We assessed dose and duration of risperidone treatment, weight, changes
      in calorie intake, and frequency of aggressive behavior. RESULTS: Of the 50
      patients, 39 had adequate data for analysis. Thirty-seven of the 39 patients
      gained weight with a mean of 18.8 lb (8.3 kg) over about 2 years. Twenty of the
      37 patients were calorie restricted. Three of the 20 calorie-restricted patients
      lost weight at a rate of 0.2 lb (0.1 kg) per month. The other 17 calorie
      restricted patients and the 17 patients who were not calorie restricted continued
      to gain weight at a rate of 0.8 lb (0.4 kg) per month over about another 2 years
      of treatment. The amount of weight gain was not dose related. Calorie restriction
      led to no deterioration in behavior. CONCLUSION: The current investigation lends
      support to data that note weight gain with risperidone in adults with mental
      retardation. It suggests that calorie restriction does not lead to weight loss or
      behavioral deterioration and that weight gain is not dose related.

PMID- 11247097
TI  - Assessing the comparative effectiveness of antidepressant therapies: a
      prospective clinical practice study.
AB  - BACKGROUND: Although efficacy studies suggest equal potency among antidepressant
      treatments, their effectiveness in clinical practice appears more variable,
      particularly in that the newer antidepressants may be less effective in either
      more severe depression or the melancholic subtype of depression. We pursue some
      factors that may impact the effectiveness of antidepressant treatments in a
      clinical sample. METHOD: A sample of 182 patients with DSM-IV major depressive
      disorder was assessed at baseline and 12 months later to establish treatments
      provided, identify patients who had recovered from the index episode, and
      quantify likely treatment determinants. Four systems for distinguishing patients
      with melancholic and non-melancholic depression were examined to assess for
      differential effects of the antidepressant strategies across those subtypes.
      RESULTS: Multimodal therapy (commonly, psychotherapy combined with an
      antidepressant drug) and patients' frequent attribution of recovery to
      spontaneous improvement made for difficulty in disentangling recovery
      determinants. After excluding a spontaneous improvement component,
      electroconvulsive therapy (ECT) and the irreversible monoamine oxidase inhibitors
      (MAOIs) appeared to be the most effective therapies across the sample, while the
      reversible inhibitor of monoamine oxidase-A (RIMA) appeared to be the least
      effective. The distinct gradient of suggested effectiveness of various strategies
      appeared to be contributed to principally by the varied effectiveness of
      alternate treatments across the melancholic subtype, whereby ECT, tricyclic
      antidepressants, and MAOIs were the most effective, and the selective serotonin
      reuptake inhibitors (SSRIs), RIMAs, and antipsychotic drugs were much less
      effective. For the nonmelancholic disorders, the effectiveness of SSRIs appeared
      to be comparable with that of older antidepressants. CONCLUSION: Although most
      patients received a physical treatment, they commonly judged psychotherapy and
      spontaneous improvement to be influential in their recovery. Reasons for such
      attributions are worthy of clarifying studies. Despite patients' concerns about
      the side effects and stigma of ECT as well as the side effects associated with
      the older antidepressants, these therapies were rated as more helpful by patients
      and were more strongly associated with recovery-than the newer antidepressant
      drugs. Such overall results are compatible with an earlier study undertaken by us
      involving an independent sample and retrospective data. The overall gradient is
      clarified by studying depressive subtypes, allowing an important conclusion.
      Although the newer and older antidepressant drugs may be of similar effectiveness
      in nonmelancholic depression, the newer agents appear comparatively inferior for
      the treatment of melancholia, findings that have clinical implications and
      perhaps inform us about the pathogenesis of melancholia.

PMID- 11247098
TI  - Mannitol-induced acute manic state.

PMID- 11247099
TI  - Sexual dysfunction and fluvoxamine therapy.

PMID- 11247100
TI  - Priapism associated with polypharmacy.

PMID- 11247101
TI  - Treatment of tardive dyskinesia with donepezil.

PMID- 11247102
TI  - Addition of risperidone to clozapine therapy in chronically psychotic inpatients.

PMID- 11247103
TI  - Antidepressant treatment and global tests of coagulation and fibrinolysis.

PMID- 11247104
TI  - Switching versus augmentation: a prospective, naturalistic comparison in
      depressed, treatment-resistant patients.
AB  - OBJECTIVE: (1) To directly compare the effectiveness of switching antidepressants
      with augmenting them in depressed patients who do not respond to an initial
      adequate trial and (2) to determine whether there is a decreased likelihood of
      response to a second switch or augmentation trial in those patients who did not
      respond to the first intervention for treatment-resistant depression. METHOD: In
      a naturalistic, open-label design, all depressed outpatients (DSM-IV criteria)
      who were treatment resistant were prospectively assessed. Short- and long-term
      outcomes of switching versus augmentation were compared using the Clinical Global
      Impressions scale. RESULTS: In the acute phase, 37 (50.0%) of 74 subjects
      responded to 1 of the 2 interventions for treatment-resistant depression. Forty
      five percent (N = 17) and 56% (N = 20) of the patients who had their
      antidepressant switched or augmented, respectively, responded to that
      intervention. Nearly three fourths (71.4%) of the acute responders maintained
      their response through 6 months of follow-up. In 18 patients who did not respond
      to the first switch or augmentation, 9 (50.0%) responded to a second trial.
      CONCLUSION: Switching antidepressants was somewhat less effective than
      augmentation, although this difference was not statistically significant. For
      patients who do not respond to an augmentation or switch, our results suggest
      that a second trial for treatment-resistant depression may be as effective as the
      first.

PMID- 11247105
TI  - The psychopharmacology of sex, Part 1: Neurotransmitters and the 3 phases of the
      human sexual response.

PMID- 11247106
TI  - Prevention of recurrent postpartum depression: a randomized clinical trial.
AB  - BACKGROUND: Women who have suffered one episode of postpartum-onset major
      depression (PPMD) comprise a high-risk group for subsequent episodes. We
      conducted a double-blind, randomized clinical trial to test the efficacy of
      nortriptyline in the prevention of recurrent PPMD. METHOD: Nondepressed women who
      had at least one past episode of PPMD (Research Diagnostic Criteria) were
      recruited during pregnancy. Subjects were randomly assigned to nortriptyline or
      placebo. Treatment began immediately postpartum. Each subject was assessed for 20
      sequential weeks with the Hamilton Rating Scale for Depression and Research
      Diagnostic Criteria for recurrence of major depression. RESULTS: No difference
      was found in the rate of recurrence in women treated with nortriptyline compared
      with those treated with placebo. Of 26 subjects who took nortriptyline
      preventively, 6 (0.23, 95% exact confidence interval [CI] = 0.09 to 0.44)
      suffered recurrences. Of 25 subjects who took placebo, 6 (0.24, 95% exact CI =
      0.09 to 0.45) suffered recurrence (Fisher exact p = 1.00). CONCLUSION:
      Nortriptyline did not confer additional preventive efficacy beyond that of
      placebo. The rate of recurrence of PPMD (one fourth of women) was unacceptably
      high.

PMID- 11247107
TI  - Delusionality and response to open-label fluvoxamine in body dysmorphic disorder.
AB  - BACKGROUND: Available data suggest that the delusional variant of body dysmorphic
      disorder (BDD), a type of delusional disorder, may respond to serotonin reuptake
      inhibitors (SRIs) and that delusionality (lack of insight) in BDD may improve
      with SRI treatment. However, this research has been hampered by the lack of a
      reliable and valid scale to assess delusionality. METHOD: Thirty subjects (21
      women, 9 men; mean age = 33.3 +/- 9.0 years) with DSM-IV BDD were prospectively
      treated with open-label fluvoxamine for 16 weeks. Subjects were assessed at
      regular intervals with the Brown Assessment of Beliefs Scale (BABS), the Yale
      Brown Obsessive Compulsive Scale Modified for BDD (BDD-YBOCS; a measure of BDD
      severity), and other instruments. The BABS is a reliable and valid 7-item,
      semistructured, clinician-administered scale that assesses current delusionality.
      RESULTS: In this prospective, open-label study, 63% of BDD subjects responded to
      fluvoxamine. Delusional and nondelusional subjects had similar improvement in BDD
      symptoms. In addition, insight significantly improved in both delusional and
      nondelusional subjects. Baseline BABS scores did not contribute significantly to
      endpoint BDD-YBOCS scores in a regression analysis. CONCLUSION: Degree of
      delusionality did not predict fluvoxamine response, and delusionality
      significantly improved. These findings are preliminary and require confirmation
      in controlled trials. The implications of these findings for other types of
      delusions requires investigation.

PMID- 11247108
TI  - Long-term olanzapine treatment: weight change and weight-related health factors
      in schizophrenia.
AB  - BACKGROUND: Weight change and the weight-related health factors of nonfasting
      serum glucose, serum cholesterol, and diastolic blood pressure levels were
      analyzed in patients with DSM-III-R schizophrenia and related disorders who
      received treatment with olanzapine for up to 3 years, and comparisons were made
      to patients treated with haloperidol. Baseline body mass index (BBMI; kg/m2) and
      dose (mg/day) were investigated as predictors of long-term weight change
      experienced during olanzapine treatment. METHOD: This analysis retrospectively
      examined 573 patients receiving olanzapine and 103 patients receiving haloperidol
      for 39 weeks or more from a study of 1,996 patients randomly assigned 2:1 to
      either olanzapine, 5 to 20 mg/day, or haloperidol, 5 to 20 mg/day. After 6 weeks
      of acute therapy, patients continued for 1 year or more with either double-blind
      or open-label olanzapine therapy or double-blind haloperidol therapy. RESULTS:
      Mean weight gain for olanzapine-treated patients observed for a median of 2.54
      years trended toward a plateau after the first 39 weeks of treatment with a last
      observation-carried-forward mean weight change of 6.26 kg (13.8 lb) and a median
      of 5.90 kg (13.0 lb). This was significantly higher than that for haloperidol
      treated patients, whose mean weight gain was 0.69 kg (1.5 lb) after 1.15 years (p
      < .001). Patients with higher BBMI (> 27.6) gained significantly less weight
      during treatment with olanzapine than their lighter counterparts (BBMI < 27.6) (p
      < .001). The effect of olanzapine dose on weight was not significant (p > or = .
      183). Median serum glucose at endpoint was not significantly associated (p =
      .096) with weight change for olanzapine. Median serum cholesterol and diastolic
      blood pressure for olanzapine-treated patients at endpoint showed a relationship
      with weight change that was statistically (p < or = .001) but not clinically
      significant. The difference in incidence of elevated serum glucose, cholesterol,
      or diastolic blood pressure between olanzapine and haloperidol therapy groups was
      not different (p > .05). CONCLUSION: Mean weight gain during olanzapine treatment
      trended toward a plateau after the initial 39 weeks of treatment with no further
      significant gain out to 3 years. Higher BBMI was predictive of a lower long-term
      weight gain, while dose was not a significant predictor of greater longer term
      weight change. The relationship between weight change and glucose was not
      statistically significant. The association between weight change and changes in
      cholesterol as well as changes in diastolic blood pressure was statistically
      significant but not considered clinically relevant based on the ranges observed.

PMID- 11247109
TI  - Diversity and development of circadian rhythms in the European rabbit.
AB  - Three main concerns underlie this review: 1) The need to draw together the widely
      dispersed information available on the circadian biology of the rabbit. Although
      the rabbit is a classic laboratory mammal, this extensive body of information is
      often overlooked by chronobiologists, and despite several advantages of this
      species. In terms of its general biology the rabbit is the best studied
      laboratory mammal in the wild, it demonstrates a wide variety of robust circadian
      functions, and being a lagomorph, it provides a useful comparison with more
      commonly studied rodent species. 2) The need to more fully exploit a
      developmental approach to understanding circadian function, and the particular
      suitability of the rabbit for this. Female rabbits only visit their altricial
      young for a few minutes once every 24 h to nurse, and survival of the young
      depends on the tight circadian-controlled synchronization in behavior and
      physiology of the two parties. Patterns of circadian rhythmicity in neonatal pups
      associated with nursing do not form a smooth continuum into weaning and adult
      life, and may reflect the action of separate mechanisms operating in their own
      right. 3) Using information from the first two points, to emphasize the diversity
      and complexity of circadian rhythms underlying behavioral and physiological
      functions in adult and developing mammals. Information accruing on circadian
      functions in the rabbit makes it increasingly difficult to account for these in
      terms of one or two regulatory mechanisms or "oscillators." Thus, it is argued
      that in addition to the reductionist, molecular approaches currently dominating
      much of chronobiology, the study of circadian systems as emergent characteristics
      of whole organisms operating in complex environments merits special attention.

PMID- 11247110
TI  - Impaired modulation of circadian rhythms in patients with diabetes mellitus: a
      risk factor for cardiac thrombotic events?
AB  - Serious adverse cardiovascular events, including myocardial infarction, sudden
      cardiac death, and stroke, frequently result from rupture of atherosclerotic
      plaques with superimposed thrombosis and exhibit a pronounced circadian
      rhythmicity, peaking in the morning hours. Two potentially synergistic mechanisms
      play a pathogenic role in the circadian variation of arterial thrombotic events.
      A morning surge in sympathetic activity alters hemodynamic forces and predisposes
      vulnerable coronary atherosclerotic plaques to rupture. Day-night variations of
      hemostatic and fibrinolytic factors result in morning hypercoagulability and
      hypofibrinolysis, promoting intraluminal thrombus formation at the same time when
      the risk for plaque rupture is highest. Diabetic patients have a very high
      cardiac event rate but fail to show normal circadian fluctuations in the
      occurrence of myocardial infarction. Alterations in the circadian variation
      autonomic tone, blood pressure, and the thrombotic-thrombolytic equilibrium have
      been documented in diabetic patients. These include reduced or absent 24-h
      periodicity in autonomic tone, fibrinolytic activity, and thrombotic tendency,
      and a blunted decline in nocturnal blood pressure. Disruption of these circadian
      rhythms explains the lack of significant circadian distribution of cardiac events
      in diabetic patients. Moreover, the loss of these normal biorhythms results in a
      continuous susceptibility to thrombotic events throughout the day and may
      contribute to the excess cardiovascular mortality and morbidity in these
      patients.

PMID- 11247111
TI  - Valproic acid has temporal variability in urinary clearance of metabolites.
AB  - The reasons for the intra- and interindividual variability in the clearance of
      valproic acid (VPA) have not been completely characterized. The aim of this study
      was to examine day-night changes in the clearance of 3-oxovalproate (3-oxo-VPA),
      4-hydroxy-valproate (4-OH-VPA), and valproic acid glucuronides under steady
      state. Six diurnally active healthy male volunteers ingested 200 mg sodium
      valproate 12 hourly, at 0800 and 2000, for 28 days. On the last study day, two
      sequential 12-h urine samples were collected commencing at 2000 the evening
      before. Plasma samples were obtained at the end of each collection. Following
      alkaline hydrolysis, urine was analyzed for concentrations of VPA, 3-oxo-VPA, and
      4-OH-VPA. A separate aliquot was assayed for creatinine (CR). The plasma
      concentrations of VPA, 3-oxo-VPA, 2-en-VPA, and CR were determined. The analysis
      of VPA and its metabolites was performed by GC-MS. There was an increase in
      plasma 3-oxo-VPA concentration at 0800, sampling as compared to 2000 sampling (p
      < .05). The urinary excretion of 3-oxo-VPA and VPA glucuronides were decreased
      between 2000 and 0800, compared to between 0800, and 2000, by 40% and 50%
      respectively (p < .05). These results indicate a nocturnal decrease in renal
      clearance of 3-oxo-VPA rather than a decrease in the beta-oxidation of VPA at
      night. These differences were not explained by differences between the sampling
      periods in CR excretion. These results indicate the importance of collecting
      samples of 24-h duration when studying metabolic profiles of VPA.

PMID- 11247112
TI  - Time-keeping system of the eel pout, Zoarces viviparus.
AB  - Observations on the rhythmic activity of 71 juvenile specimens of the inter-tidal
      blenny Zoarces viviparus reveal an endogenous pattern of swimming at three
      different periodicities. Circatidal swimming, with activity peaks phased to high
      water or the ebb of the subjective 12.4-h tides, was found in 50 fish and was the
      predominant pattern seen immediately after collection, when the rhythm generally
      persisted for between 3 and 12 cycles. Discrete activity peaks, with a free
      running period of approximately 24 h were also evident in the swimming pattern of
      eight fish. A circadian influence was also manifest as a modulation in amplitude,
      phase shifts and changes in free-running period of the circa-tidal rhythm.
      Overall, the activity level declined with time but those fish that remained
      active long enough showed a semi-lunar rhythm, with maximum activity at the time
      of the spring tides. A comparison of the behavior of animals collected at
      different times of the year suggests a seasonal variation in the persistence of
      circatidal swimming. The results are consistent with a control system involving
      circatidal, circadian, and semi-lunar oscillators.

PMID- 11247113
TI  - Circadian locomotor activity rhythms of the diurnal Indian palm squirrel in
      constant light.
AB  - The parametric or tonic effects of light were studied in a recently established
      diurnal circadian model-the Indian palm squirrel, Funambulus pennanti. Sixteen
      squirrels (7 female, 9 male) were housed individually under varying constant
      light conditions (0.1 lux to 46 lux) with gross locomotor activity continuously
      monitored. Free-running period (tau), amplitude, mesor and day-to-day stability
      of the activity rhythm were determined using modified periodogram and iterative
      harmonic analyses, while the ratio of activity to rest time was estimated by eye
      fit. The main findings were as follows: 1) tau did not vary between sexes or
      between light conditions, although a trend for tau to lengthen when light
      intensity was increased was noted; 2) amplitude and mesor did not show sex
      differences, but both sexes showed a decrease in amplitude and mesor when light
      intensity was decreased; 3) the stability of the activity rhythm was greater in
      males than in females, and a trend was observed for rhythm stability to decrease
      when light intensity was reduced. These descriptive data contribute to the
      growing literature on this diurnal species.

PMID- 11247114
TI  - Relationship between the annual rhythms in melatonin and immune system status in
      the tropical palm squirrel, Funambulus pennanti.
AB  - Melatonin (MEL) regulation of seasonal variation in immunity has been studied
      extensively in temperate mammals. This report is the first on a tropical mammal,
      the Indian palm squirrel, F. pennanti. In response to the annual environmental
      cycle, we studied the rhythms of plasma MEL and the immune parameters of total
      blood leucocytes, absolute blood lymphocytes and blastogenic responses of blood,
      thymus and spleen lymphocytes. We found that in parallel with MEL all the immune
      parameters increased during the month of April onward, when natural day length,
      temperature, humidity and rainfall were increasing. Maximum values occurred
      during November (reproductively inactive phase) when the values of all the
      physical factors were comparatively low. Lowest values occurred during January
      March (reproductively active phase) when the values of the physical factors were
      lowest. In order to establish a clear interrelationship between the pineal MEL
      and the immune system function, we manipulated these squirrels with exogenous MEL
      (25mg/100 g B wt/day) at 1730 h during their pineal inactive phase (March) while
      another group was pinealectomized (Px) during November when their pineal was
      active. The MEL injection significantly increased all the immune parameters,
      while Px decreased them significantly. Hence, we suggest that MEL is immuno
      enhancing for this tropical squirrel, and plays an important role in the
      maintenance of its immunity in accordance with the seasonal changes in
      environmental factors and gonadal status.

PMID- 11247115
TI  - Nonlinear behavior of human respiratory movement during different sleep stages.
AB  - To investigate the nonlinear properties of respiratory movement during different
      sleep stages, we applied an algorithm proposed by Grassberger and Procaccia to
      calculate the correlation dimension in rapid eye movement and non-rapid eye
      movement sleep. We also tested for nonlinearity in respiratory movement by
      comparing the correlation dimension for the original data with that for surrogate
      data. The study population included eight healthy volunteers. We recorded
      respiratory movement and the sleep electroencephalogram for 8 h. The correlation
      dimension for respiratory movement was 3.28+/-0.19 (mean +/- SD) during rapid eye
      movement sleep, 2.31+/-0.21 during light sleep (stage I) and 1.64+/-0.25 during
      deep slow-wave sleep (stage IV). Thus, the correlation dimension differed
      significantly by sleep stage (p < 0.001): it was least during stage IV sleep and
      greatest during REM. The correlation dimension for the original data also
      differed from that for surrogate data, confirming nonlinearity in original data.
      The results suggest that the nonlinear dynamics of respiratory movement in sleep
      changes with sleep stage, presumably due to the information processing by the
      cerebral cortex. The increased correlation dimension for respiratory movement in
      REM sleep may be related to increased cortical information processing associated
      with dreaming.

PMID- 11247116
TI  - Repeated assessment of the endogenous 24-hour profile of blood pressure under
      constant routine.
AB  - The impact of environmental and behavioral factors on the 24-h profile of blood
      pressure (BP) has been well established. Various attempts have been made to
      control these exogenous factors, in order to investigate a possible endogenous
      circadian variation of BP. Recently, we reported the results of the first
      environmentally and behaviorally controlled laboratory study with 24-h recordings
      of BP and heart rate (HR) during maintained wakefulness. In this constant-routine
      study, a pronounced endogenous circadian rhythm of HR was found, but circadian
      variation of BP was absent. This result suggested that the circadian rhythm of BP
      observed in earlier controlled studies, with sleep allowed, was evoked by the
      sleep-wake cycle as opposed to the endogenous circadian pacemaker. In order to
      verify our previous finding during maintained wakefulness, we repeated the
      experiment five times with six normotensive, healthy young subjects. Statistical
      analyses of the hourly measurements of BP and HR confirmed the replicable
      presence of an endogenous circadian rhythm of HR, as well as the consistent
      absence of an endogenous circadian variation of BP. Thus, this study provided
      additional evidence that the 24-h profile of BP--as observed under normal
      circumstances--is the sole result of environmental and behavioral factors such as
      the occurrence of sleep, and has no endogenous circadian component.

PMID- 11247117
TI  - Is melatonin circadian rhythm a physiological feature associated with healthy
      longevity? A study of long-living subjects and their progeny.
AB  - The study investigates the circadian rhythm (CR) of urinary 6-sulphatoxy
      melatonin (aMT6s) in long-living (longevous) subjects and their progeny. The aim
      is to detect whether or not the melatonin CR is a physiological feature
      associated with healthy longevity. The aMT6s CR was investigated in 10 longevous
      subjects, 8 of their children and 9 of their grandchildren, all in good health.
      Control data were obtained respectively from 13 adult subjects and 9 young
      subjects, in good health, but characterized by a negative family history for
      longevity. All the subjects were born and living in the same city. The study was
      performed in the summer of 1996. The aMT6s CR was found to persist in longevous
      subjects, being characterized by a lower mesor and amplitude. The aMT6s CR was
      found not to show properties consistently different in children and grandchildren
      as compared respectively to their adult and young controls. Because of its
      preservation in longevous subjects, it can be argued that the melatonin CR is a
      physiological feature associated with healthy longevity. Because of the
      comparability of aMT6s CR in children and grandchildren, with respect to their
      controls without a positive family history of longevity, it can be argued that
      the melatonin CR is not a marker that can be used for an earlier identification
      of the candidates for longevity.

PMID- 11247118
TI  - [Distribution of biological particles in two-phase systems of water soluble
      polymers and salts].
AB  - The paper discusses the problems of purification of Provachek's rickettsias used
      to prepare typhus vaccines and diagnostic kits. The currently available agents
      contain many admixtures of rickettsias products, more commonly yolk and chick
      embryo yolk sack cell detritus, which make it impossible to determine the true
      antigenic properties of rickettsias in the context of protection and diagnosis.
      By applying the well-known principle of distribution of biological particles in
      the two-phase systems of water soluble polymers, investigations were made to
      examine the distribution of rickettsias and their infected biological mass in the
      system: polyethylene glycol-6600, sodium-500 dextran sulfate, potassium
      phosphate, sodium chloride in order to prepare agents of pure rickettsias. It has
      been found that rickettsias are distributed in the polymer-enriched phase, their
      number and the degree of purity when isolated from the infected biological mass
      depends on the capacity of an interphase wherein tissue detritus sorption occurs.

PMID- 11247119
TI  - [Development and design of a sampling kit for microbiological studies].
AB  - The paper deals with the development and design of a kit for choosing samples
      from various objects for microbiological studies. The studies clarified the
      composition of the set and requirements for the complete set and its parts. The
      design of this set parts was made and the design documents were drawn up for
      manufacturing the sampling set. A programme and procedures for microbiological
      and pilot tests of the kit were developed and its trials were performed.

PMID- 11247120
TI  - [Use of laser flow-type fluorescence aerosol particle counter to evaluate the
      concentration of microbes in the surface air under high dust content].
AB  - The paper deals with the use of a laser flow-type fluorescence aerosol particle
      counter to evaluate the concentrations of microbes in the surface air under high
      dust content. Various circuits of flow-type optic aerosol recorders are analyzed.
      Flow spectral luminescence analysis of some particles flow while exciting the
      fourth harmonics of a pulse laser on yttrium-aluminium garnet with neodymium by
      ultraviolet radiation is shown to be the most optimum method for indication of
      individual aerosol particles. Experiments were conducted on the authors' model of
      a pilot plant based on this method. The model of a laser flow-type optic analyzer
      was developed for experimental studies that give a clear display of biological
      aerosols in complex aerosols. The laser flow-type analyzer-based unit developed
      may provide a fluorescence signal of aerosol particles in the flow of a sample
      and that light diffusion signal from them at an exciting light wavelength of 266
      nm. Experiments with BVC aerosols and soil dust particles were conducted in
      different regions of Russia. They showed it possible to detect and to rapidly
      calculate soil microorganisms by laser flow-type fluorescence assay of individual
      particles when excited by ultraviolet radiation.

PMID- 11247121
TI  - [Sulforodamine 101: novel effective marker in liposomal immunoassay].
AB  - The new fluorescence marker Sulforodamine 101 that allows one to avoid a labour
      consuming stage of purification of a marker substance (for example, calceine,
      other fluorescein derivatives) from hydrophobic admixtures that reduce the
      storage of a liposomal reagent was used in liposomal immunoassay. Sulforodamine
      101 shows the maximum increase in a fluorescence signal when liposomes are
      destroyed with encapsulated marker, which is 45 times greater than does
      Sulforodamine B (8 times) and comparable with calceine (30 times). The
      comparative studies using liposomes containing calceine and Sulforodamine 101
      have indicated that they are similar storage and sensitivity (50 ng/ml) of
      liposomal test system as determined by the concentration of F. tularensis
      polysaccharides in solutions.

PMID- 11247122
TI  - [Rapid indication of microbiological damage and biodegradation of structural
      materials in space vehicles].
AB  - The study was undertaken to design a kit of indicators for rapid detection and
      group identification of microbes causing biological damages to the materials.
      Indication is accomplished by dropwise colorimetric reaction for which modified
      chromatographic materials serve as substrates. Reactions are made by the
      indicators whose design allows reagents and samples to be measured on board space
      vehicles. The designed kit of indicators detects microorganisms, biodegrade
      products, and identifies them by groups: vegetative or spore-forming bacteria,
      and lower fungi. The paper considers the characteristics of colorimetric
      reactions and an algorithm of group identification of microbes by the respective
      combination of positive and negative results of the reactions. It also presents
      data on the sensitivity levels of tests provided by the kit, which were obtained
      from laboratory and field ground tests.

PMID- 11247123
TI  - [The human genome project as a scientific background of preventive medicine].
AB  - Conspicuous achievements in the Human Genome Project have already found
      spectacular implementation in both basic research and practice. The Human Genome
      Diversity, Functional Genomics, and numerous Social Programmes are under way and
      they are rapidly expanding the scientific area induced by the Human Genome
      Project. Its practical implication is mainly confined to molecular medicine and
      to its quickly growing area Predictive (Preventive) Medicine. The paper briefly
      considers the existing concepts of molecular genetic tests of "predisposition"
      genes, including such groups as "environmental" genes and "trigger"-genes to
      detect subjects highly susceptible to different common multifactorial diseases
      and the expediency for testing the genes whose mutations cause diseases showing
      their manifestations at the late stage. Evidence is provided for that there is a
      progressive increase in population, family, and personal predisposition gene DNA
      databanks. There is need for close interaction between researchers and all strata
      of society, including the clergy, governments, political parties, etc. in order
      to optimize perception of scientific achievements of modern genetics and their
      effective used for the welfare of mankind.

PMID- 11247124
TI  - [Problems of disinfection and decontamination in the biological protection and
      prevention of contagious diseases].
AB  - The problems of biological protection of the general population and military
      staff against biological hazard sources, primarily against biological terrorism
      and military threat underlie works on the design of new disinfectants having a
      universal spectrum of antimicrobial action and less ecological hazard than
      currently available ones. Elimination of biological hazard require effective
      chemical disinfectants that can completely inactivate microbes of unknown
      etiology as rapidly as possible and that cause the minimum damage to
      environmental objects. The disinfectant PFK of various modifications is evaluated
      in terms of the requirements of that ecological and chemical concept aimed at
      testing chemicals entering the environment.

PMID- 11247126
TI  - [Atherogenesis as a reflection of immune inflammation in the vascular wall].
AB  - Despite numerous basic and applied studies into the pathogenesis and treatment of
      atherosclerosis, there is no theory which could explain the development of the
      whole complex of changes united under the term "atherosclerosis". Examining the
      causes of atherosclerosis disclosed a pathogenetic association of the
      immunoregulatory signal CD40-CD40L with the occurrence of arterial
      atherosclerotic lesions. Studies of the immune mechanisms responsible for the
      pathogenesis of atherosclerosis (autoimmune complexes containing oxidative
      modification of LDL, T and B lymphocytes, inflammation mediators, hemoadhesive
      molecules, and immunoregulatory molecules showed the leading role of autoimmune
      mechanisms in atherosclerosis. The conceptual result of the studies is that the
      authors have elucidated the leading role of immune inflammation in the appearance
      and development of arterial atherosclerotic lesions. The development of a new
      concept of assessing the pathogenesis of atherosclerosis in the context of immune
      inflammation in the vascular wall opens new vistas for the treatment of this
      disease.

PMID- 11247125
TI  - [Increased proinflammatory cytokine production by human peripheral lymphocytes
      treated with glucocorticoids].
AB  - Glucocorticosteroids (GC) are the true immunomodulators that can depress and
      enhance immune reactions. Hormone-activated GC receptors (GCR) change the
      transcription of many genes, resulting in modified immune responses. The
      direction of immunomodulation under which GC act depends on their level, the
      quantity and state of GCR, the amount of different cytokines and cytokine
      receptors and other immunoactive molecules. The modulation of proinflammatory (IL
      1 beta, IL-6, TNF-alpha) cytokine production by human peripheral lymphocytes
      treated with a wide range of dexamethasone (10(-6)-10(-12) mol) in the serum-free
      culture medium was observed in the present study. Enhanced or suppressed cytokine
      release depends on GC doses, intermittent or continuous contact with the hormone
      and cell environment. The magnitude of changes in IL-1 beta and TNF-alpha
      production was similar (parallel stimulation or depression) while diminished TNF
      alpha was observed simultaneously with enhanced IL-6 production and vice versa.
      The suppression of proinflammatory cytokine production by GC is well documented.
      The experimental conditions of increased cytokine release with dexamethasone in
      the serum-free culture medium can serve as a model of investigation in false
      results of steroid immunosuppression.

PMID- 11247127
TI  - [Elimination of autologous cytotoxicity at the level of nonspecific adhesion].

PMID- 11247128
TI  - [Preparation and use of chemical disinfectants in biological protection and
      prevention of contagious diseases : ecological aspects].
AB  - Ecological requirements to reduce negative effects of chemical disinfectants were
      one on major determinants the line of works to develop and introduce novel
      compounds that are environmentally safe hydrogen peroxide derivatives. The paper
      analyzes the possible routes of entering different fluorine compounds into the
      environment when disinfecting measures are made at therapeutical-and-preventive
      institutions, when emergencies occur at microbiological synthesis plants. The
      maximum concentration of a chemical that has no effect on biochemical processes
      when it is continuously used at sewage works is chosen as a safe (permissible)
      level. Preliminary calculations show that the use of PFK for disinfection will
      not pollute the environment with fluorides.

PMID- 11247129
TI  - [Effects of regulator peptides on expression of mannose-containing membrane
      structures in leukocytes in acute stress].
AB  - We have investigated the influence of regulative peptides (oxytocin, pituitrin,
      thyroid-releasing hormone and SNC) on the expression of mannose-containing
      membrane structures (MCMS) of lymphocytes and neutrophils in acute stress (3-hour
      immobilization on the back). MCMS were assayed by the indirect lectin-peroxidase
      test. We have found that MCMS-expression of lymphocytes significantly decreased
      but neutrophil MCMS-expression changed in different directions. SNC and thyroid
      releasing hormone decreased and MCMS expression increased, respectively. Acute
      stress activated MCMS expression of lymphocytes. This activation was
      uncorrectable by the investigated peptides, MCMS expression of neutrophils was
      corrected by oxytocin, thyroid-releasing hormone and pituitrin. Thus, MCMS
      expression of leukocytes changed as a multimodal system by acute stress and
      peptide administration. This system may take part in pathogenesis of the stress
      reaction.

PMID- 11247130
TI  - [Immunomodulating and antioxidant effects of magnetic and laser irradiation
      combined with administration of beta-carotene, essentiale, and riboxine during
      cold stress].
AB  - We studied effects of beta-carotine, essentiale and riboxine on immunometabolic
      effects induced by laser or magnetic laser radiation in intact rats and rats
      exposed to immersion cold. We found that combination of laser or magnetic laser
      radiation with administration of beta-carotine or riboxine more effectively
      corrected antioxidant status and immunological reactivity than radiation alone or
      in combination with essentiale.

PMID- 11247131
TI  - [Age changes in properties of myofibrillary creatine phosphokinase enzyme in the
      rat myocardium during stress].
AB  - The activity of the myofibrillar isoenzyme creatine phosphokinase (CPK) in the
      heart inhibits with age. This may be explained by impaired association of CPK
      with myofibrils. The immobilization stress led to a sharp fall in CPK activity in
      its decreased affinity to the substrate. Changes in the catalytic properties of
      myofibrillar CPK in the myocardium of adult stressed rats raise effectiveness of
      its function in altered cardiac metabolism in stress.

PMID- 11247132
TI  - [Adaptation of the myocardium to psychoemotional stress in patients with
      myocardial infarction and painless ischemia].
AB  - To assess features of heart adaptation to psychoemotional stress in patients with
      myocardial infarction (MI), we studied contractile and pump functions of the left
      ventricle in conditions of modelled informational stress. A total of 36 MI
      patients were examined using informational stress, echocardiography,
      electrocardiography, impedance plethysmography. We established variants of
      biological rhythms of the heart in MI patients with painless myocardial ischemia
      of psychogenic origin.

PMID- 11247133
TI  - [Stress phenomenon. Emotional stress and its role in pathology (continuation)].

PMID- 11247134
TI  - [Hydrodynamic efficiency of various forms of free DNA].
AB  - DNA of blood plasma is the factor which corrects hydrodynamic resistance (HR) of
      blood flow and provides Thomes' effect. As comparative hydrodynamic effectiveness
      of various plasma DNA forms (nucleoprotein, thread and denaturated DNA isolated
      standardly from human leukocytes) remains unknown, the in vitro test identified
      HR of the flow of the above DNA forms weak solutions--10(-6) to 10(-5) g/ml-
      necessary for achievement of Thomes' effect in strictly similar hydrodynamic
      conditions warranting a turbulent flow (Re 8000). Thomes' effect was confirmed in
      blood samples in its absence in low-molecular solutions (glycerine) with the same
      asymptotic viscosity. It was found that HR of the flow of synthetic polymer
      solutions producing Thomes' effect depends on its initial concentrations.
      Hydrodynamic effectiveness in the used solutions of the nucleoprotein and DNA was
      high being comparable to that of the synthetic polymer widely used in production
      for obtaining Thomes' effect.

PMID- 11247135
TI  - [Use of the novel taurine derivative for prevention of changes in the systemic
      hemodynamics induced by electric stimulation of the rabbit aorta].
AB  - The influence of a new taurine derivative on hemodynamic changes induced by
      electrostimulation of an aortic reflexogenic zone was studied. It is shown that 3
      hour electrostimulation increased total peripheral resistance and decreased
      cardiac output and aortic pressure. Intravenous infusion of the taurine
      derivative during electrostimulation normalized abnormal hemodynamic
      characteristics.

PMID- 11247136
TI  - [Clinical forms of ischemic heart disease and natural evolution of live
      information-thermodynamic systems].
AB  - Clinical forms of myocardial ischemia are considered in terms of a new approach
      towards illness formation as a violation of information exchange in a human
      organism. The latter is suggested to be an open information-thermodynamic system
      developing to a closed equilibrium stationary thermodynamic system with
      information as a factor of system stability and direction of the evolution guided
      by the second thermodynamic law.

PMID- 11247137
TI  - [Post-stress state and communicative alterations of immunity and blood].
AB  - It is shown that intact animals caged with stressed animals or in smell contact
      with natural secretions of stressed animals develop alterations of the immune
      system and peripheral blood cell composition. The decline in the genesis of
      antibodies to T-dependent antigen is related to the animals' gender and occurs at
      the height of poststress immunodepression.

PMID- 11247138
TI  - [Use of physiotherapeutic technology in correcting risk factors for
      cardiovascular diseases].

PMID- 11247139
TI  - [Meteopathogenic mechanisms of exacerbating ischemic heart disease in an arid
      zone].
AB  - In arid zone of Uzbekistan summer heat discomfort aggravates the course of
      ischemic heart disease, provokes meteopathic reactions which we call
      "meteorological strain syndrome". In this season anginal attacks, episodes of
      arrhythmia and coronary failure become more frequent especially in patients over
      70 years of age and migrants.

PMID- 11247140
TI  - [Carbonic acid baths and magnetolaser in treating diabetic angiopathies].

PMID- 11247141
TI  - [Acupunctureal electrostimulation in rehabilitating patients with gunshot
      injuries to the peripheral nerves].
AB  - The efficacy of acuelectrostimulation (AES) and some aspects of the mechanism of
      motor function recovery were studied in 46 patients with gunshot injuries of 66
      nerves and plexuses using cliniconeurophysiologic examination. It is shown that
      AES promotes regression of motor, sensitive and vegetovascular disturbances. A
      positive effect of AES on structural and restorative processes in the patients
      with gunshot injuries of peripheral nerves was confirmed by the results of
      electrophysiologic studies (EMG, ENMG) which register an increase in muscular
      biopotential amplitude, M-response, recovery of conduction or enhancement of
      impulse conduction velocity in the motor fibres of the peripheral nerves, an
      increase of functioning motor units. After a treatment course an increase of H
      reflex and M-response amplitudes in the musculus soleus and medial musculus
      gastrocnemius of calf developed in the patients with gunshot injuries of lower
      extremity peripheral nerves this indicating improvement of the state of afferent
      and efferent links of neuromuscular system.

PMID- 11247142
TI  - [Therapeutic efficacy of electrophoresis of humic acids from sea mud in
      osteoarthritis].
AB  - Therapeutic action and efficiency of electrophoresis of humic acids (HA) from
      Khaapsaluskaya sea mud were studied in 97 patients with osteoarthrosis in
      comparison with electrophoresis of physiologic salt solution (PS). HA
      electrophoresis was found more effective (p < 0.01) as providing more potent
      anesthetic effects and more beneficial effect on joint function than PS
      electrophoresis (p < 0.005 and p < 0.01).

PMID- 11247143
TI  - [Criteria for the efficacy of the therapeutic action of preformed factors in
      fracture of cotyloid cavity].

PMID- 11247144
TI  - [Method for treating inflammatory diseases of the uterine appendages using the
      eplir mud preparation].
AB  - Ultraphonophoresis of 1% oil solution of eplir in patients with acute
      inflammation of the uterine appendages as an adjuvant to drug therapy enhances
      the latter by immediate (anesthetic, antiexudative action), short-term
      (immunocorrection) and long-term (preservation and restoration of reproductive
      function, prevention of chronicity) treatment results.

PMID- 11247145
TI  - [Laser therapy as a method of eliminating tolerance to nitrates and potentiation
      of their action].
AB  - Infrared laser therapy was examined for the ability to eliminate tolerance to
      nitrates and to potentiate their action. Laser radiation (0.85 micron) reduced
      tolerance to nitrates and potentiated nitrates action. This was evident from a
      rise in threshold load power, less frequent and weaker myocardial ischemia.

PMID- 11247147
TI  - [Some aspects of the development of physiotherapy from the State Institute of
      Physiotherapy until the present].

PMID- 11247146
TI  - [Turpentine white emulsion baths in the rehabilation in patients with sexual
      dysfunctions].
AB  - 100 patients with sexual dysfunction (SD) and 20 SD patients took turpentine
      white emulsion baths and sodium chloride baths, respectively. The turpentine
      baths were given with step-by-step rise in turpentine concentration from 20 to 50
      ml per 200 l of water, temperature 36-37 degrees C, duration of the procedure 10
      15 min. The course consisted of 10-12 procedures which were conducted daily or
      each other day. The turpentine baths were more effective than sodium chloride
      baths (85 vs 50%, respectively).

PMID- 11247148
TI  - [Role of the State Institute of Physiotherapy in setting up physiotherapy and
      preparing staff].

PMID- 11247149
TI  - [Requirement for studying the origin of therapeutic mud (part 1)].

PMID- 11247150
TI  - [Economic aspects of sanitorium-resort and health-improving services].

PMID- 11247151
TI  - [Rehabilitation of athletes with cardiovascular pathology].

PMID- 11247152
TI  - [Use of low-intensity laser radiation in injuries to the extremities].

PMID- 11247153
TI  - [Auricular reflexotherapy in Reiter's disease].

PMID- 11247154
TI  - [Effect of Belokurikha resort water, obtained in biological objects].

PMID- 11247155
TI  - [Modification of experimental fever reaction by various physiotherapeutic
      factors].
AB  - The study of the effects of different physical factors (UV radiation, infrared
      radiation, magnetic field) on the course of endotoxemia and its sequelae has
      found that dynamics and severity of the temperature and pain reactions,
      biochemical parameters in the animals noticeably depend on the nature of the
      physical factor and initial general condition of the animal.

PMID- 11247156
TI  - [Physiotherapy of hypertension in elderly persons].

PMID- 11247157
TI  - [Effect of infrared radiation and combination of it with constant and alternating
      magnetic fields on the recuperative processes in the thymus, liver, and blood of
      stressed rats].
AB  - Changes in thymic cells activity in stressed animals were compared to the level
      of 11-oxycorticosteroids in the blood and antioxidant hepatic activity in
      exposure of the hepatic projection region and solar plexus to varying doses of
      infrared radiation and its combination with constant or alternating magnetic
      fields. It was shown that combined action of constant or variable (pulsed with
      negative semiperiods) magnetic fields and infrared radiation in the above
      exposure promotes optimal conditions for regeneration in stressed rats.

PMID- 11247158
TI  - [Free radical oxidation and food antioxidants in allergic diseases].
AB  - The article reviews experimental and clinical data that supports free radicals
      participation in allergic reactions development. Free radical reactions were
      shown to take place in activation of first and second order target cells, in
      cellular interactions participating in allergic inflammation; besides these free
      radicals initiate lipid peroxidation in target cells and produce shift in
      eicosanoid metabolism. The review discusses participation of free radicals in
      allergy pathogenesis and proposes the expedience of food antioxidants utilization
      in complex treatment and prophylactic of allergic diseases.

PMID- 11247159
TI  - [Effects of biologically-active dietary supplement from marine biology on
      cholinesterase activity and blood lipid peroxidation in humans].
AB  - Influence of dietary supplement Tinrostim-C on cholinesterase (ChE) activity and
      serum lipids peroxidation (LP) in patients whose work connects with emotional
      stress was examined. Activity of ChE was measured by Ellman calorimetric method
      (with acetylthiocholin as substrate), LP--by fluorimetric method with malone
      dialdehyde. Tinrostim-C was given three times a day in 0.5 g. On the 10th day of
      taking the preparation an activity of serum ChE increased 23.5% higher and had
      been staying higher during the whole period of observation. In vitro experiments
      showed an activating effect of Tinrostim-C and piracetam for serum ChE. The level
      of LP being initially higher was decreasing to values close to normal and had
      been staying at decreased level during the whole period of observation.

PMID- 11247160
TI  - [Effects of bioflavonoids on the toxicity of T-toxin in rats. A biochemical
      study].
AB  - The enrichment of a diet of rats by flavonoids of milk thistle, Silybum marianum,
      reduced toxicity of T-2 toxin and was accompanied by reduction of a degree of
      change of total and nonsedimentable activity of lysosomal enzymes and microsomal
      xenobiotic metabolizing enzymes.

PMID- 11247161
TI  - [Effects of bioflavonoids on the toxicity of T-toxin in rats. A morphological
      study].
AB  - Subacute toxicity of T-2 toxin in rats was characterized by a primary defeat of
      liver, thymus, spleen and intraorgan arteries. In 75% of animals found out
      increase of the size and adipose infiltration of a liver, in all animals-
      reduction of the size of thymus (sharp) and spleen (moderate) and pronounced
      hypoplasia of lymphoid tissue. In the majority of rats vacuolation of cytoplasma
      of smooth-muscular walls of coronary and intrarenal arteries was revealed. In
      animals received T-2 toxin against a background of a diet with addition a flour
      from seeds of milk thistle with high contents of flavonoids, described
      morphological changes were expressed to a lesser degree and were observed less
      often. Moderate periportal adipose infiltration of a liver was revealed in 30% of
      animals, occupancy by cells of lymphoid tissue increased, the quantity and sizes
      of vacuoles in walls of vessels decreased.

PMID- 11247163
TI  - [The 70th anniversary of the RAMN Institute of Nutrition: basic landmarks in its
      foundation and development].

PMID- 11247162
TI  - [Medical and biological problems of relationship between food product quality and
      free radical oxidation state in humans].
AB  - Relation between quality of nutrition products and condition not infectious
      morbidity of the population of Republic Adygea, connected with development of
      free-radical processes are shown. The levels of contamination of products by
      nitrates, pesticides, heavy metals are investigated, the contents of vitamins
      antioxidants is established. Was applied biotesting fats with use test-culture T.
      piriformis which had shown in 50% of cases subacute toxicity of the investigated
      samples and 6.2%--acute toxicity. In 1994-1998 is marked the growth of morbidity
      of the population a cataract (21.3%) and stomach ulcer (61.8%), diabetes (51.5%)
      on a background of insignificant decrease of morbidity in general. The priority
      directions in optimization antioxidative status of organism and decrease of free
      radical pathologies level.

PMID- 11247164
TI  - [Study of the role of the feeding factor in the development of induced
      experimental mammary cancer in rats].
AB  - It is studied the influence of two types of experimental diets on rats origin
      mammary tumors. The first diet was enriched by pig's fat and 2nd diet contained
      soybean protein and induced N-nitrozo-N-methylurea (MNM). The tumors of rat's
      mamma were induced by intramammary injections of N-nitrozo-N-methylurea in area
      of the 2nd left mamma in dose 2.5 mg per rat once a week during 5 weeks. The rats
      of control group were not exposed to any additional influences except for a
      carcinogenic one. The rats of first and second subgroup were fed with lard (50
      mg/kg) and soybean protein (200 mg/kg) during 30 weeks. It was shown that lard
      evinced cocarcinnogenic action on the origin of mammary tumors to stimulating
      their growth and development while the soybean protein considerably reduced
      frequency of mammary tumors and slowed the time of their appearance.

PMID- 11247165
TI  - [Contents of water-soluble vitamins in canned fish and seafood].
AB  - Data of contents of vitamins (B1 and B2, C, PP) in production from gidrobionts is
      given. Is established, that the process of sterilization of canned food from
      gidrobionts in to container provides significant (almost twofold) decrease
      (reduction) of vitamins B1 [symbol: see text] B2, smaller losses of vitamin C
      (less than 30%) and proves to be true sufficient stability (almost on 85-90%) to
      action of high temperatures (120 degrees C) of vitamin PP. The canned food from
      sea gidrobionts represent the certain interest basically as a source of vitamin
      PP, and canned food "Herring smoked in oil"--vitamin B2. The canned food
      "Skobljanka from cucumber and fish" can be considered as a source of vitamins B2,
      C, PP.

PMID- 11247166
TI  - [Effects of diet therapy including eiconol on clinical and metabolic parameters
      in patients with type 2 diabetes mellitus].
AB  - It was investigated the influence of a diet supplemented with PUFA omega-3
      ("Eiconol") on dynamic of basal and postprandial glycemia, blood pressure, lipid
      levels, parameters of lipid peroxidation in 60 patients with non-insulin
      dependent diabetes mellitus. Fish oil ("Eiconol") was used as a dietary
      supplement of PUFA omega-3. The results of investigations indicated that a diet
      supplemented with "Eiconol" (8 g/day) increased the effect of dietary therapy in
      correction of essential hypertension and atherogenic lipids. It was not the
      worsening of the glycemia and activation of lipid peroxidation.

PMID- 11247167
TI  - [Study of fatty acid composition of cell membranes during the use of soya oil in
      diet therapy of patients with cardiovascular diseases].
AB  - Anti-atherogenic diet supplemented with 20 g soy oil has been analyzed in
      patients with coronary artery disease and high blood pressure. The vegetable PUFA
      omega-3 and omega-6 from soy oil have been found to change physical, biological
      and chemical property of membranes; improved clinical condition as well as to
      modify erythrocyte membrane fatty acid composition.

PMID- 11247168
TI  - [Analysis of modern concepts concerning the role of processed soybean products in
      diet therapy of patients with cardiovascular diseases].
AB  - In this review the analysis of chemical structure of soybeans is given, are
      indicated and the outcomes of evaluation of medical and preventive efficiency of
      use soy and products of its processing in a feed of the patients with
      cardiovascular diseases on data of experimental researches and clinical natural
      observations are discussed.

PMID- 11247169
TI  - [Role of glutamine in enteral nutrition in intestinal insufficiency].
AB  - In this review the role of glutamine in enteral nutrition in intestinal
      insufficiency is shown. It is emphasized, that glutamine plays an important role
      in preservation of structure and function of intestines in normal state and under
      stressful condition.

PMID- 11247170
TI  - [Sources of energy values and contribution of various products to maintenance of
      chemical contents of the diet of an unorganized population of Moscow].
AB  - With use of a method of daily reproduction at representative sample of an
      unorganized population of inhabitants of Moscow the sources of energy value and
      contribution of various products to supply organism by the basic food substances
      (protein, fats, carbohydrates and cholesterol) are investigated. Is established
      that the nutrition structure is obviously debalanced. More quarters of daily diet
      energy is provided for consumption of animal fats and simple sugars. Is shown
      that the main part of fat (2/3) enters in organism as the "latent" fats of animal
      products, the fats "in the pure form" half consist from butters. The main source
      of the saturated fats and cholesterol for men are meat, and for women--the dairy
      products. 12% researched refuse purified sugars.

PMID- 11247171
TI  - [Organization of lung digital X-ray fluorography and its introduction into the
      health care services of Russia].
AB  - Based on comprehensive study of the capacities of digital X-ray fluorography
      (DXRF), the authors give their views on two main aspects of its use. These are
      firstly the most acceptable organizational forms of lung DXRF into the health
      care services of Russia and, secondly, its place in the diagnosis of pulmonary
      tuberculosis, lung cancer, chronic nonspecific lung diseases, and mediastinal
      tumors. As for its organization and introduction, the authors are against the
      fact that film fluorography should be rapidly replaced by DXRF. They give
      recommendations based on the reasonable and stepwise introduction of DXRF, which
      may rule out their negative perception versus the present attitude to the so
      called prophylactic film fluorography. In the part dealing with diagnosis that
      analyzes 955 cases of various lung diseases (from over 8000 DXRFs) verified by
      different studies (morphological, cytological, etc.) and chest X-ray computed
      tomography, the authors show the results of monitoring imaging, by demonstrating
      all its potentialities. At the same time they recommend that image printing
      fixing should be also rather widely employed. In the authors' opinion, DXRF may
      become the method of choice in detecting pulmonary tuberculosis, lung cancer,
      chronic nonspecific lung diseases, and mediastinal tumors.

PMID- 11247172
TI  - [Radiation diagnosis of bronchioloalveolar cancer].
AB  - The paper analyzes the results of examination of 260 patients with
      bronchioloalveolar cancer (BAC) who were followed up at the Russian Research
      Center of Radiology and Roentgenology for 30 years. It provides its clinical, X
      ray, and morphological manifestations and classification and the methodological
      aspects of differential diagnosis. An optimum radiation diagnosis programme has
      been drawn up, which involves currently available procedures, including computed
      tomography. The morphological forms of BAC are given in detail.

PMID- 11247173
TI  - [Experience with computerized technologies in the diagnosis of respiratory
      diseases in children].
AB  - The paper summarizes the experience gained in using an automatic X-ray study
      system (AXRSS) for 5 years. AXRSS is successful in tackling the task of having a
      display image of the quality that allows one to make X-ray diagnosis with the
      same confidence as that of an X-ray film.

PMID- 11247174
TI  - [Magnetic resonance imaging in the diagnosis of renal neoplasms : MRI -
      histopathological comparison].
AB  - The study evaluates the diagnostic of the MRI in the discovery and characterizing
      renal neoplasms. The principle of the comparative study of MRI, other diagnostic
      modalities and histopathological data was applied by the author, using a large
      pool statistically significant clinical material (419 cases). Renal cell
      carcinoma--the most wide-spread renal parenchyma's tumor, was selected as a
      morphological model (302 cases). As a result of this investigation, the MRI
      semiotics of renal cell carcinoma was more precisely defined and detailed and
      this method's high level of sensitivity (98.4%) was detected, concerning the
      detection of such a type of pathology. The MRI data reliably reflect (r > 0.8; P
      < 0.05) the true morphological structure of the tumor's growth, the secondary
      tumor's tissue alterations and its interaction with surrounding anatomical
      formations. Thus, MRI is appreciated as a method of choice for oncological
      urology.

PMID- 11247175
TI  - [Comparative assessment of hemodynamic parameters in ventricular septal defect,
      obtained by Doppler echocardiography and catheterization of cardiac cavities].
AB  - The study was undertaken to assess hemodynamic parameters by Doppler
      echocardiography in patients with ventricular septal defect (VSD) and pulmonary
      hypertension. Seventy-two patients aged 5 months to 9 years (mean 2.5 years) who
      had isolated VSD were examined. The authors conclude that it is possible and
      necessary to assess hemodynamics in the lesser circulation by using Doppler
      echocardiography. The method permits monitoring the time course of changes in the
      right heart, which makes it possible to follow the natural history of disease
      without applying invasive studies.

PMID- 11247176
TI  - [Magnetic resonance tomography of temporomandibular joint].
AB  - The paper shows the place of magnetic resonance imaging among other radiation
      diagnostic techniques in detecting abnormal changes in the temporomandibular
      joint. The authors' own data were based on the results of 315 examinations. The
      paper describes the technical features of examination of the joint and shows it
      possible to visualize different anatomic structures on T1-, T2- and Pd-weighted
      images. It also indicates the diagnostic potentialities of magnetic resonance
      imaging in identifying abnormal changes in the joint in its diseases and lesions.
      This has allowed the authors to show what is indicated for magnetic resonance
      imaging of the temporomandibular joint and that it is necessary to develop an
      algorithm of radiation diagnosis for patients with different clinical forms of
      joint diseases.

PMID- 11247177
TI  - [Postcholecystectomic ultrasound diagnosis (a review of literature)].

PMID- 11247178
TI  - [Use of artificial contrasting methods in interventional radiology].

PMID- 11247179
TI  - [The role of clinical investigations in the study of mechanisms of development of
      acquired demyelinating polyneuropathies].

PMID- 11247180
TI  - [Spectrum of neuropsychological changes in multiple sclerosis].
AB  - Early disability of patients with multiple sclerosis at the able-bodied age is
      often caused by both a neurological disorder and the difficulties of their social
      and psychological adaptation that is aggravated significantly by higher cortical
      dysfunctions and by behavioral problems. The paper presents the results of the
      dynamic neuropsychological observation of 124 patients with multiple sclerosis
      and of their first degree relatives. Even at the early stage of the disease there
      were some cognitive disorders as worse transitent verbal, semantic, visual memory
      active attention and slower sensomotor reactions; difficulties in conceptual
      mentality. The cognitive functions, the activity of the disease, an actual
      psychological state, depression for example, and the expression of brain atrophy
      and the localization of the foci are bound by the certain way. The personality
      traits of patients and their close relatives testified a possible psychosomatic
      nature of this disease.

PMID- 11247181
TI  - [Alcoholic hypomanic syndrome].
AB  - There were examined 115 patients with I and II stages alcoholism who had
      hypomaniacal syndrome. This syndrome was observed in form of "jolly hypomania" in
      the I stage of alcoholism and by more complex forms--"angry" or "obsessive"
      hypomania--in the II stage. The correlation of psychopathologic peculiarities of
      hypomania and psychological personality traits and EEG data was found.

PMID- 11247182
TI  - [The irritable bowel syndrome in mental patients].
AB  - 140 patients with the irritable bowel syndrome were examined. According to the
      results of clinical analysis of the manifestations, symptomatology and structure
      of comorbidity, two syndrome types were identified. These included those: with
      the phenomena of autonomic or conversive neurosis (89.3 and 10.7% respectively).
      The syndrome with signs autonomic neurosis were characterized by: 1) spontaneous
      or somatogenic manifestation; 2) homomorphism and stability of both abdominalgias
      and defecation disorders; 3) limitation of functional disorders in
      gastrointestinal organs; 4) syndromal and temporary (parallelism of formation and
      dynamics) comorbidity with endogenous diseases (66%) (cyclothymia, slowly
      progressive schizophrenia), hypochondriac development (16%) and anxious-phobic
      disorders (18%); 5) correlation with subclinic somatic pathology of
      gastrointestinal tract. Syndrome with the phenomena of conversive neurosis was
      characterized by: 1) psychogenically induced manifestation; 2) polymorphism and
      instability of abdomnalgias and stool disorders; 3) polymorphism of functional
      disorders of different organ systems; 4) syndromic and temporary (parallelism of
      formation and dynamics) comorbidity with subsyndromic psychic disorders:
      transitent hysterohypochondriac phobias (cardiophobia, tanatophobia)--60%,
      transitent (less than 2-3 months) hysteroaffective reactions caused by situations
      -40%; 5) none or minimal concomitant subclinical gastrointestinal pathology.

PMID- 11247184
TI  - [Ozone therapy of migraine].
AB  - Application of ozone therapy was based on the notions of a significant role of
      lipid peroxidation in the pathogenesis of migraine attacks. A therapy was
      performed in form of intravenous infusions of the ozonized physiologic solutions
      with ozone, concentration 1200 micrograms/l; a therapy course included 8-9
      procedures. 68 patients with migraine attacks, followed by the pronounced
      autonomic changes, that developed in the frequency range from 5-6 times a year to
      2-3 times a week were examined. 40 patients formed a study group and 28
      individuals control one (in a control group the physiologic solution was used
      without ozone). The intensity of a headache, the expression of an anxiety, the
      state of the vessels of the brain and some biochemical indices were determined.
      Positive dynamics of the disease was 25% higher in the study group than made up a
      those in the controls (p < 0.05). In 58% of the patients the attacks were absent
      during 3-5 months after ozone therapy; less intensity of headache was observed
      after their relapse. Improvements in the patients coincides with changes in
      biochemical parameters.

PMID- 11247183
TI  - [The experience with endolumbar application of cerebrolysin in hemispheric
      ischemic stroke].
AB  - The purpose of the investigation was to evaluate the efficiency of therapy of
      patients with hemispheric ischemic stroke with cerebrolysin (C) (using two
      different regimens of its injections) versus placebo. One endolumbar C injection
      (5 ml) made in the first 12 hours of stroke and after the subsequent therapy with
      dropwise C injections (10 ml) significantly enhanced the efficiency of therapy
      and improved the functional recovery of patients was observed 12 hours following.

PMID- 11247185
TI  - [Dynamics of mental disorders after extracerebral implantation of embryonal
      nervous tissue in epilepsy].
AB  - The paper presents the method elaborated by the authors for production, storage
      and implantation of embryonal nervous tissue (ENT). Extracerebral implantation
      was performed in 33 epileptic patients aged 2-58 years. Clinical state of the
      patients and EEG alterations were studied. Before treatment the patients' mental
      status was characterized by affective disorders, dysphoria, depression,
      exhaustion of mental processes, varying intellectual-mnestic decrease and
      behavioral disinhibition. Oligophrenia as of debility was observed in several
      cases. After implantation the pronounced positive changes in both paroxysmal
      states and overall mental status were observed in all the cases irrespective of
      their age of the patients. These clinical changes correlated with the dynamics of
      EEG changes (EEG changes were not observed in 2 individuals with positive
      clinical effects).

PMID- 11247186
TI  - [On rare forms of transient delirious states (afterword by N.M. Zharikov)].

PMID- 11247187
TI  - [Biochemical mechanisms of impaired neuroimmune interaction in multiple
      sclerosis].
AB  - Neurotransmitters and cytokines that play a key role in the mechanisms of
      interaction of the nervous and immune systems have been studied in both the blood
      and cerebrospinal fluid of 195 patients with multiple sclerosis. The findings
      suggest that neurotransmitters and cytokines play a role in the pathochemical
      mechanisms of development of the disease and that certain neurotransmitter
      systems are involved into the development of some neurological symptoms. It was
      proposed that excitotoxic mechanisms are responsible for the damages to nervous
      tissue and for death of oligodendroglial cells in multiple sclerosis. Alterations
      in norepinephrine levels and platelet serotonergic indices may be manifestations
      of compensatory protective mechanisms that resulted in activation of primarily
      suppressor T-lymphocytes. The inflammatory cytokines--interferon-gamma and tumor
      necrosis factor-alpha participate in the mechanisms of pathologic process
      activation and in the development of the disease. On the contrary, interferon
      alpha was supposed to promote remission and involved in the mechanisms of a
      favorable course of multiple sclerosis that testified the necessity of
      differential immunocorrection at different stages of the disease.

PMID- 11247188
TI  - [P300 auditory evoked potentials in schizophrenia].
AB  - P300 auditory evoked potentials were recorded in 27 schizophrenic patients in the
      standard oddball paradigm. P300 amplitude in the right frontal zone correlated
      positively with the age of the patients at the onset of disease. As compared with
      normal (18 subjects), schizophrenics showed both smaller P300 amplitudes and
      longer latencies. The findings are assumed to reflect impairment of information
      processing in schizophrenia. It is emphasized that the level of impairment is
      higher when the disease occurs in adolescence.

PMID- 11247189
TI  - [Clinical development and computed tomographic diagnosis of tumors in the
      posterior cranial fossa in children].

PMID- 11247190
TI  - [A role of phosphoinositides in the development of multiple sclerosis].

PMID- 11247191
TI  - [Modern approaches to beta-interferon application in therapy of multiple
      sclerosis].
AB  - Recently a disease-modifying treatment of multiple sclerosis (MS) became
      possible. The first choice in this kind of treatment is the use of beta
      interferons. The longest history has the studies of beta-interferon-1b, which has
      a beneficial effect on the course of MS reducing the annual exacerbation rate and
      slowing the disability progression. This kind of treatment is very expensive and
      has only a moderate influence on the disease course, only slowing its
      progression, but still are widely used and causes attention all over the world.
      The most important question is the appropriate selection of MS patients for this
      kind of treatment. Numerous regional neurological community has elaborated
      special recommendations for the use of this treatment. These recommendations are
      usually base on the data of clinical trials, own experience and current financial
      situation (to cover the high cost of this treatment). Analyses of the last data
      on the mechanisms of beta-interferons treatment showed several specific and
      nonspecific effects. In recently published studies beta-interferon-1b was shown
      to slow the progression of confirmed disability in secondary progressive MS and
      delay the switch from relapsing/remitting to secondary progressive MS. Still the
      most beneficial clinical effect is seen in relapsing/remitting cases. The problem
      of neutralizing antibodies (NAT) and treatment of possible side effects seem now
      not to be so principle. Recommendations for the selection of patients with MS for
      treatment with beta-interferon were proposed.

PMID- 11247192
TI  - [A combination of antidepressants and neuroleptics in the treatment of affective
      disorders and schizophrenia: indications, side effects and complications].

PMID- 11247193
TI  - An integrated approach to communicable disease surveillance.

PMID- 11247194
TI  - Health conditions for travellers to Saudi Arabia.

PMID- 11247195
TI  - First outbreak of Japanese encephalitis in two villages of Dharmapuri district in
      Tamil Nadu.
AB  - BACKGROUND & OBJECTIVES: Three cases of Japanese encephalitis (JE) were reported
      for the first time from two villages in Krishnagiri Health Unit district of Tamil
      Nadu during November 1999. Two children died and one developed neurological
      sequelae. A serological survey was conducted in these villages to find out the
      prevalence of JE antibodies among children below 15 yr of age in addition to the
      epidemiological investigations. METHODS: The prevalence of haemagglutination
      inhibiting (HI) antibodies to JE virus (JEV), West Nile virus (WNV) and dengue-2
      virus (DEN-2) was detected by HI test and IgM antibody capture ELISA (MAC ELISA)
      was performed to determine recent infections with JE virus. Adult mosquitoes were
      collected in the study villages and females of Culex pseudovishnui, C.
      tritaeniorhynchus and C. vishnui were tested for the presence of JE viral antigen
      by ELISA. RESULTS: Out of 146 sera samples from children below 15 yr, the
      prevalence of HI antibodies to JEV, WNV and DEN-2 virus was found to be 8.9, 3.4
      and 6.85 per cent respectively and three children had IgM antibodies to JEV. Of
      the 13 species of mosquitoes identified, C. tritaeniorhynchus (30.8%) was the
      most abundant species in the study villages. Two pools of female C.
      tritaeniorhynchus were found to be positive for JEV antigen. Fogging with 2 per
      cent pyrethrum and residual spray with 10 per cent cyfluthrin were effective in
      reducing vector density. INTERPRETATION & CONCLUSIONS: Serological investigations
      revealed that the JE virus was predominant in the study villages. In addition,
      DEN-2 and WN viruses were also prevalent. Detection of JE virus specific IgM
      antibodies in three specimens and the presence of JE viral antigen in 2 pools of
      C. tritaeniorhynchus emphasized the need for constant surveillance and monitoring
      so as to prevent future large outbreaks.

PMID- 11247196
TI  - Comparison of various conventional methods with a polymerase chain reaction assay
      for detecting methicillin-resistant & susceptible Staphylococcus aureus strains.
AB  - BACKGROUND & OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA), a
      major nosocomial pathogen world-wide, is often difficult to detect due to the
      heterogeneous nature of expression of oxacillin resistance. In the present study,
      various conventional methods were compared with polymerase chain reaction on 106
      clinical isolates of Staph. aureus for detection of oxacillin resistance.
      METHODS: A total of 106 clinical isolates of Staph. aureus were tested for
      oxacillin resistance by disc diffusion, screen agar plates (3 micrograms and 6
      micrograms/ml of oxacillin), oxacillin broth (3 micrograms/ml) and mecA based
      PCR. RESULTS: PCR detected mecA gene amplified product of 604 bp in 57 strains.
      Disc diffusion failed to detect 7 mecA positive strains but identified 5 mecA
      negative strains as oxacillin resistant. Screen agar 3 micrograms, screen agar 6
      micrograms and oxacillin broth 3 micrograms detected 55, 53 and 55 respectively
      of the 57 mecA positive strains; however, they also falsely identified 5, 3 and 3
      strains of mecA negative strains respectively as oxacillin resistant. The
      sensitivity, specificity and accuracy of disc diffusion, 3 micrograms screen
      agar, 6 micrograms screen agar and 3 micrograms oxacillin broth against PCR as
      gold standard were as follows: 87.7, 89.9 and 88.7 per cent; 96.5, 89.8 and 93.4
      per cent; 93.0, 93.9 and 93.4 per cent; 96.5, 93.9 and 95.3 per cent
      respectively. INTERPRETATION & CONCLUSIONS: The present study demonstrated that
      disc diffusion test was least reliable and 3 micrograms broth had the highest
      sensitivity and specificity when compared with PCR for detection of oxacillin
      resistance. Because of variations among the methods, a combination of tests
      should be used for the accurate detection of MRSA till new guidelines by an
      appropriate body are formulated.

PMID- 11247197
TI  - A four year follow up study of filaria specific IgE response in individuals with
      hydrocele.
AB  - BACKGROUND & OBJECTIVES: Hydrocele is the most common clinical manifestation in
      males infected with Wuchereria bancrofti. IgE response to a filarial allergen
      Sd30 was evaluated in hydrocele patients living in a W. bancrofti endemic region
      of Orissa, India. METHODS: IgE levels to Sd30, an antigenic fraction isolated
      from Setaria digitata, were determined by ELISA in sera from patients of
      filariasis (n = 93). IgG and IgM levels were also determined. RESULTS: It was
      observed that microfilaraemic patients with hydrocele (n = 16) exhibited
      considerably reduced (P < 0.01) IgE levels in comparison to hydrocele patients
      without microfilariae (n = 27) and to other filarial groups (elephantiasis,
      asymptomatic microfilaraemics). The reduced IgE response in microfilariae
      positive patients with hydrocele persisted even after a gap of four years in the
      majority of patients. INTERPRETATION & CONCLUSIONS: The results show low IgE
      levels in microfilaraemic patients with hydrocele in comparison to other groups
      in filaria endemic regions. The exact mechanism of this reduction in IgE is not
      known but these patients make a distinct group in filaria endemic regions and
      should be considered separately for immunological evaluation.

PMID- 11247198
TI  - Multicentric study of efficacy of periconceptional folic acid containing vitamin
      supplementation in prevention of open neural tube defects from India.
AB  - BACKGROUND & OBJECTIVES: A folic acid containing multivitamin preparation was
      evaluated for its efficacy in preventing recurrence of open neural tube defect
      (NTD) in a blind, placebo-controlled randomized trial. The trial was carried out
      at the five centres in India, viz., Bangalore, Mumbai, Lucknow, New Delhi and
      Pune. METHODS: The preparation contained 4 mg of folic acid besides calcium,
      iron, zinc and vitamins A, B1, B2, B6, C, D and nicotinamide. The placebo
      contained calcium and iron only. A total of 466 women with previous history of
      giving birth to a child with open NTD were included in the trial (231 in the
      vitamin group and 235 in the placebo group). The supplementation was given for at
      least one month prior to conception and up to three months after conception. All
      women were offered antenatal diagnosis with screening of maternal serum alpha
      foetoprotein (AFP) and ultrasound. RESULTS: Pregnancy outcome with reference to
      recurrence of NTD was unknown in 137 women in the vitamin group and 142 in the
      placebo group. The recurrence of open NTD in the vitamin group was 2.92 per cent
      compared to 7.04 per cent in the placebo group, a reduction by about 60 per cent.
      The difference, however, was not statistically significant (P = 0.06).
      INTERPRETATION & CONCLUSIONS: The study seems to support the role of
      periconceptional folic acid supplementation in prevention of recurrence of NTDs
      in the Indian population. The reason for high recurrence rate observed in the
      placebo group requires further investigation.

PMID- 11247199
TI  - Effects of massage & use of oil on growth, blood flow & sleep pattern in infants.
AB  - BACKGROUND & OBJECTIVES: The present study was undertaken to investigate if
      massage with oils commonly used in the community for massage in infancy is
      beneficial. METHODS: Full term born healthy infants (n = 125), 6 +/- 1 wk of age,
      wt > 3000 g were randomly divided into five groups. Infants received (i) herbal
      oil, (ii) sesame oil, (iii) mustard oil, or (iv) mineral oil for massage daily
      for 4 wk. The fifth group did not receive massage and served as control. The
      study tools were anthropometeric measurements; microhaematrocrit; serum proteins,
      creatinine and creatine phosphokinase; blood flow using colour doppler and sleep
      pattern. RESULTS: Massage improved the weight, length, and midarm and midleg
      circumferences as compared to infants without massage. However, in the group with
      sesame oil massage increase in length, midarm and midleg circumferences by 1.0,
      0.9 and 0.7 cm, respectively was significant (P < 0.05, < 0.01 & < 0.05). There
      was no change in microhaematocrit, serum: proteins, albumin, creatinine and
      creatine phosphokinase between both the groups. The femoral artery blood
      velocity, diameter and flow improved significantly by 12.6 cm/sec, 0.6 cm and
      3.55 cm3/sec respectively in the group with sesame oil massage as compared to the
      control group. Massage improved the post massage sleep, the maximum being 1.62 h
      in the sesame oil group (P < 0.0001). INTERPRETATION & CONCLUSIONS: Massage in
      infancy improves growth and post-massage sleep. However, only sesame oil showed
      significant benefit.

PMID- 11247200
TI  - Association of drug levels & pharmacokinetics of carbamazepine with seizure
      control.
AB  - BACKGROUND & OBJECTIVES: A sizeable number of epilepsy patients remain
      uncontrolled with carbamazepine (CBZ) monotherapy. While the therapeutic plasma
      concentration range of CBZ is only vaguely defined, pharmacokinetic differences
      in the disposition of CBZ among subjects could be responsible for the inadequate
      control of seizures in some. This study was aimed at associating serum CBZ levels
      with seizure control and elucidating any pharmacokinetic differences between
      patients with controlled and uncontrolled epilepsy. METHODS: The study was
      conducted in 16 controlled and 15 uncontrolled adult epileptic patients receiving
      CBZ monotherapy for the previous 3 or more months, without any dosage change.
      Blood samples were drawn from the patients before and 0.5, 1, 2, 3, 4, 8, 12 and
      24 h after ingestion of their total daily dose of CBZ. Serum CBZ levels were
      measured by HPLC and the pharmacokinetic parameters were calculated. RESULTS: The
      uncontrolled epileptic patients were receiving a higher daily dose of CBZ
      (difference not significant). The trough and peak serum CBZ levels were
      relatively higher in the uncontrolled group, and at no time point were the drug
      levels lower in these patients compared to the controlled group. The absorption
      kinetics, volume of distribution and plasma half life of CBZ were similar in the
      two groups. Thus, non-attainment or non-maintenance of therapeutic CBZ level or
      other pharmacokinetic difference was not responsible for occurrence of seizures
      in the uncontrolled patients. A high percentage of patients with generalised
      tonic clonic seizures (73%) and simple partial seizures (SPS) with generalisation
      (66%) were controlled by CBZ, while SPS and complex partial seizures (CPS) were
      largely uncontrolled. INTERPRETATION & CONCLUSIONS: It appears that
      pharmacodynamic resistance of the seizure to CBZ rather than pharmacokinetic
      factors is responsible for lack of efficacy of CBZ in nonresponding epileptic
      patients.

PMID- 11247201
TI  - Are the complexities of women's sexual function reflected in the new consensus
      definitions of dysfunction?

PMID- 11247202
TI  - The sexual pain disorders: a desexualized approach.

PMID- 11247203
TI  - Pertinent points.

PMID- 11247204
TI  - Physiologic applications of the new female sexual response classification system.

PMID- 11247205
TI  - My personal distress over the inclusion of personal distress.

PMID- 11247207
TI  - An external perspective on the report of the International Consensus Development
      Conference on Female Sexual Dysfunction: more work to be done.

PMID- 11247206
TI  - Report of the International Consensus Development Conference on Female Sexual
      Dysfunction: a view from down under.

PMID- 11247208
TI  - Clinical and research perspective.

PMID- 11247209
TI  - Ideal female sexual function.

PMID- 11247210
TI  - A call for non-proprietary peer-reviewed research.

PMID- 11247211
TI  - Musings on the report of the International Consensus Development Conference on
      Female Sexual Dysfunction: definitions and classifications.

PMID- 11247212
TI  - Small print and conspicuous omissions: commentary on the "FSD" classification
      report.

PMID- 11247213
TI  - How Japanese culture affects the sexual functions of normal females.

PMID- 11247214
TI  - Penetration disorder: dyspareunia exists on the extension of vaginismus.

PMID- 11247215
TI  - After reading the report of the International Consensus Conference on Female
      Sexual Dysfunction.

PMID- 11247216
TI  - Critical overview of the new consensus-based definitions and classification of
      female sexual dysfunction.

PMID- 11247217
TI  - Satisfaction and distress: disjunctions in the components of sexual response.

PMID- 11247218
TI  - Understanding female sexual dysfunction and the consensus conference: this is
      progress?

PMID- 11247219
TI  - Do we need a new classification system for female sexual dysfunction? A comment
      on the 1999 consensus classification system.

PMID- 11247220
TI  - Receptivity and personal distress: considerations for redefining female sexual
      dysfunction.

PMID- 11247221
TI  - The impact of female sexual dysfunction in the evaluation and management of the
      impotent patient.

PMID- 11247222
TI  - Are we ready for this classification system?

PMID- 11247223
TI  - Vaginismus is better not included in sexual pain disorder.

PMID- 11247224
TI  - New diagnostic categories for female sexual dysfunction: does the falling tree
      make a sound if no one is there to hear it?

PMID- 11247225
TI  - Meeting sexual dysfunction again for the first time.

PMID- 11247226
TI  - Female sexuality comes out of the psychiatric closet.

PMID- 11247227
TI  - Historical and international context of nosology of female sexual disorders.

PMID- 11247228
TI  - Strategic planning in research and development is needed in female sexual
      dysfunction.

PMID- 11247229
TI  - Another procrustean bed for female sexual functioning.

PMID- 11247230
TI  - A physiatrist's views regarding the report of the International Consensus
      Conference on Female Sexual Dysfunction: potential concerns regarding women with
      disabilities.

PMID- 11247231
TI  - New classification on female sexual dysfunction: some reflections on the
      consensus report.

PMID- 11247232
TI  - The consensus-based classification of female sexual dysfunction: barriers to
      universal acceptance.
AB  - Although the CCFSD attempts to clarify and modify the existing definitions of
      female sexual dysfunctions, the current authors (a sex therapist and a sex
      researcher) believe that the classification system has significant flaws that
      will prevent its widespread acceptance and application. The major concern is that
      the CCFSD is based on the triphasic model of sexual response. The triphasic model
      is based on male sexual response and does not take into account the documented
      variety of ways that women respond sexually. Instead, the parameters of male
      sexual response are extrapolated to women. The current authors suggest an
      alternative approach that considers a woman's subjective as well as physiological
      responses, and includes pleasure and satisfaction as characteristics of normal
      sexual function. A reconsideration of the CCFSD model is suggested and an
      alternative approach is offered.

PMID- 11247233
TI  - The "consensus" conference on female sexual dysfunction: conflicts of interest
      and hidden agendas.

PMID- 11247234
TI  - Classification of sexual dysfunctions in women.

PMID- 11247235
TI  - Female sexual dysfunction: definitions and classifications.

PMID- 11247236
TI  - Conceptualizing women's sexual problems.

PMID- 11247237
TI  - [Indications to tympanotomy at early stages of exudative otitis media].
AB  - 82 patients with exudative otitis media were treated surgically. Tympanotomy with
      revision of the auditory tube, retrotympanum and hypotympanum accompanied with
      reconstruction of the tympanic cavity was conducted. The effect of the surgery
      was the highest in early disease (3.5-6.5 weeks).

PMID- 11247238
TI  - [Radionuclide tests of cerebral circulation in the assessment of treatment of
      sensorineural hearing loss].
AB  - Examination and treatment results are available for 59 patients with acute and
      chronic neurosensory hypoacusis. Cerebral circulation was investigated at
      radionuclide carotid arteriography and radionuclide single-photon emission
      computed tomography. Arterial flow to the brain, microcirculation of the gray
      matter and venous outflow from the cranial cavity were studied before and after
      the course of quantum hemotherapy.

PMID- 11247240
TI  - [Red cell rheology in patients with purulent-inflammatory diseases of the nose
      and paranasal sinuses].
AB  - The study of rheological properties of red cells from peripheral blood in 61
      patients with pyoinflammatory diseases of the nasal and paranasal sinuses has
      revealed defective red cell deformability, augmentation of their aggregation,
      alterations in their shape and volume. The severity of rheological disorders
      directly correlated with severity of intoxication and inflammation. Pathogenetic
      grounds are provided validating correction of hemorheological abnormalities.

PMID- 11247239
TI  - [Detection of the central hearing defects in persons exposed to industrial noise
      by duration of the rise and fall of sound signals].
AB  - Hearing was studied using speech, audiometer MA-31 and rise and fall of loudness
      in 365 workers exposed to industrial noise only and 86 workers exposed to noise
      and dust containing lead. Identification of the front of growing loudness was
      impaired more in persons exposed to lead-containing dust; therefore they have
      more serious central hearing defects.

PMID- 11247241
TI  - [Prognostication and treatment of fronto-spheno-ethmoiditis in patients with post
      traumatic deformities of the upper and middle parts of the face].
AB  - Different types of frontosphenoethmoiditis in patients with posttraumatic
      deformities of the upper and middle facial regions including deformation of the
      naso-orbito-ethmoidal, naso-fronto-orbito-ethmoidal and sphenoidal complexes are
      described. Mechanisms of development of posttraumatic sinusitis are considered
      regarding type of the trauma. Clinical symptoms and diagnosis, problems of
      reconstructive interventions, variants of treatment policy are discussed.

PMID- 11247244
TI  - [Cochlear implantation with implant Combi 40+ produced by MED-El].
AB  - The paper reports three cases of cochlear implantation using implant Combi 40+
      produced by Med-El (Austria). Short-term postoperative testing results
      demonstrate an appreciable progress in hearing. Changes in speech discrimination
      and speech production are evaluated.

PMID- 11247243
TI  - [Computer-assisted audiometry].
AB  - A computer audiometer has been designed on the computer using program
      "Audiometry". No special devices are needed. This computer audiometric complex
      can perform all kinds of behavioral audiometry: tonal threshold, suprathreshold,
      speech and in a free sound field.

PMID- 11247242
TI  - [Clinical effectiveness of Duracef in children with ENT inflammation].
AB  - 106 children aged 4 to 14 years received duracef for different acute and chronic
      (exacerbation) ENT inflammation. The drug proved highly effective in acute
      diseases of the parynx, paranasal sinuses and ear. In exacerbations of chronic
      inflammatory diseases it was insufficiently effective. In acute inflammation use
      of duracef is beneficial as it is effective, inexpensive, low toxic, convenient
      in administration, is well tolerated, friendly to the intestine.

PMID- 11247245
TI  - [Potentiation of local anesthesia in endonasal surgery].
AB  - An original method of buccal administration of the drugs (by means of chewing
      gum) was tried in 30 patients aged 18-33 years. The drugs (ketrodol--0.5 mg/kg,
      diazepam--0.15 mg/kg, clofelin--1 microg/kg) were used to potentiate local
      anesthesia in operation--submucosal resection of the nasal septum under novocain
      solution anesthesia. Control 15 patients were operated under local anesthesia
      with morphine premedication (dose 10 mg). Adequacy of anesthesia was assessed by
      parameters of central and peripheral hemodynamics. Local anesthesia with morphine
      significantly activated sympathoadrenal system. Hyperdynamia was secured at the
      expense of accelerated cardiac rhythm with relatively low myocardial performance.
      Premedication with the chewing gum allowed to avoid pressor responses to the
      trauma in moderate hyperdynamia with adequate cardiac performance and minimal
      shifts in myocardial contractility.

PMID- 11247246
TI  - [Chronic tonsillitis: therapeutic and diagnostic approaches].
AB  - The article is a brief review of clinical and topographic anatomy of the palatine
      tonsils. Their role in formation of general and local immunity is shown.
      Etiological and pathogenetic aspects of chronic tonsillitis are considered: most
      frequent causing agents, underlying pathogenetic and immunological mechanisms.
      B.S. Preobrazhensky's and V.T. Palchun's clinical classification of chronic
      tonsillitis is presented. New approaches to etiopathogenetic treatment of chronic
      tonsillitis are described.

PMID- 11247248
TI  - [Methodology and design of research in otorhinolaryngology].

PMID- 11247247
TI  - [Immune preparation IRS-19 in the treatment of inflammation in the upper
      respiratory tracts].

PMID- 11247249
TI  - [A rare case of paratonsillitis and parapharyngitis complicated by acute purulent
      otitis media, mastoiditis and facial nerve paresis].

PMID- 11247250
TI  - [Laryngeal leiomyosarcoma].

PMID- 11247251
TI  - [A gigantic oropharyngeal fibropapilloma].

PMID- 11247252
TI  - [The development of ozena in a child suffering from anhydrotic ectodermal
      dysplasia].

PMID- 11247253
TI  - [Vestibular neuronitis].

PMID- 11247254
TI  - [An update on neurofibromatosis type 2 (bilateral vestibular schwannoma, acoustic
      neuroma)].

PMID- 11247255
TI  - [Report on the activity of international symposium "Tonsils and Adenoids"].

PMID- 11247256
TI  - [Immune status of patients with exudative otitis media before and after
      dimephosphon treatment].
AB  - General immunological reactivity and nonspecific resistance were studied in 50
      patients with exudative otitis media (EOM) treated with oral dimephosphon (a
      course of 14 days). Blood serum immunoglobulins and lymphocyte subpopulations
      were measured with single radial immunodiffusion and flow cytofluorimetry,
      respectively. Multivariate correlation analysis of immune status made with a
      special computer program gave grounds to assert that dimephosphon promotes active
      reaction of immune system which results in positive changes in T-cell, humoral
      and neutrophilic-phagocytic links of immunity.

PMID- 11247257
TI  - Technologist-performed double-contrast barium enema: United Kingdom experience
      and relevance for screening.

PMID- 11247258
TI  - Colorectal cancer screening of high-risk individuals.

PMID- 11247259
TI  - Detection of eosinophilic myocarditis using contrast-enhanced magnetic resonance
      imaging: case report.

PMID- 11247260
TI  - What to do when a misreading is discovered.

PMID- 11247261
TI  - Geographic variation in the number of authors on scientific abstracts.
AB  - OBJECTIVE: To determine if there was statistically significant geographic
      variation in the number of authors on abstracts of the 1999 Radiological Society
      of North America (RSNA) Scientific Assembly. METHODS: Information on type of
      presentation, number of authors listed in each presentation and country of origin
      was obtained for 2450 abstracts from the 1999 RSNA Scientific Assembly (1292 for
      scientific sessions, 1158 for scientific exhibitions). RESULTS: In scientific
      sessions, there were significantly more multiauthor (> 6 authors) presentations
      from Japan (32%, p < 0.001) and Germany (19%, p = 0.004) than there were from
      North America (United States and Canada) (11%). There were also significantly
      more multiauthor scientific exhibitions from Japan (29%, p < 0.001) than from
      North America (9%). Overall, the percentages of multiauthor presentations from
      Japan (30%, p < 0.001) and Germany (18%, p < 0.001) were significantly higher
      than those from North America (10%). CONCLUSION: There seems to be significant
      geographic variation in the number of authors credited on scientific
      presentations.

PMID- 11247263
TI  - Bladder stone caused by an ectopic intrauterine contraceptive device: case
      report.

PMID- 11247264
TI  - Local complications after limb-salvage surgery for pediatric bone tumours: a
      pictorial essay.
AB  - The prognosis for patients with bone sarcoma treated with LSS has improved
      considerably over the past 2 decades, but this has also lead to an increase in
      the number of complications requiring treatment. Imaging plays an important role,
      not only in assessing the primary tumour, but also in identifying postsurgical
      complications. Plain radiography demonstrates the majority of the complications
      associated with LSS and remains the mainstay of follow-up imaging. Complications
      such as fractures are common and warrant frequent plain film follow-up. Imaging
      with scintigraphy, MRI and CT should be tailored to the patient's clinical
      history, type of surgery and suspected complications. A baseline postoperative
      bone scan examination can be helpful for comparisons with subsequent scans for
      the detection of complications. Sonography should be considered if infection is
      suspected. Finally, tumour recurrence may be frequent enough to consider more
      extensive use of MRI.

PMID- 11247262
TI  - Stereotaxic percutaneous core biopsy versus surgical biopsy of nonpalpable breast
      lesions using a standard mammographic table with an add-on device.
AB  - OBJECTIVE: To determine the accuracy of using a regular mammographic table with
      an add-on device for biopsy of nonpalpable breast lesions in women in a community
      hospital setting. PATIENTS AND METHODS: During a 3-year period, 70 consenting
      women (39-80 years of age) with a nonpalpable mammographically suspicious lesion
      on routine screening mammography underwent 14-gauge automated percutaneous core
      biopsies, immediate needle localization and lumpectomy. The needle and surgical
      biopsy results were independently classified into 1 of 5 categories: cancer,
      fibroadenoma, fibrocystic change, normal or other. RESULTS: The procedure was
      well tolerated, and all core specimens yielded adequate tissue for pathologic
      evaluation. There were 3 episodes of vasovagal reaction. There was complete
      agreement in histologic findings in 64 cases (91%), including 22 of 24 cancers
      (92%). The overall agreement for categorizing lesions was 91% (kappa = 0.88), and
      there was 97% agreement (kappa = 0.94) for the classification of cancer versus
      benign lesion. CONCLUSION: The results are similar to those of studies performed
      with dedicated prone equipment. Stereotaxic core biopsies can be done safely and
      accurately in a community hospital setting with relatively inexpensive
      nondedicated mammographic equipment.

PMID- 11247265
TI  - Magnetic resonance imaging findings in tuberculous meningoencephalitis.
AB  - OBJECTIVE: To evaluate the efficacy of magnetic resonance imaging (MRI) for
      distinguishing tuberculosis from other types of meningoencephalitis. PATIENTS AND
      METHODS: MRIs of 100 patients with tuberculous (50), pyogenic (33), viral (14),
      or fungal (3) meningoencephalitis were analyzed independently by 2 radiologists.
      Number, size, location, signal characteristics, surrounding edema, and contrast
      enhancement pattern of nodular lesions; location and pattern of meningeal
      enhancement; extent of infarct or encephalitis and hydrocephalus were evaluated.
      RESULTS: Contrast-enhancing nodular lesions were detected in patients with
      tuberculous (43 of 50 patients), pyogenic (9 of 33), and fungal (3 of 3)
      infections. No nodules were detected in patients with viral meningoencephalitis.
      Using the criteria of 1 or more solid rim or homogeneously enhancing nodules
      smaller than 2 cm, the sensitivity, specificity and accuracy for diagnosing
      tuberculous meningitis were 86.0%, 90.0% and 88.0%, respectively. CONCLUSION:
      Magnetic resonance imaging is useful in distinguishing tuberculous from pyogenic,
      viral and fungal meningoencephalitis.

PMID- 11247266
TI  - Residents' corner. Answer to case of the month # 80. Congenital pericardial
      defect. Diagnosis: pericardial defect with right ventricular herniation.

PMID- 11247267
TI  - Colorectal cancer screening in Canada.

PMID- 11247268
TI  - Characterization of wet massing behavior of silicified microcrystalline cellulose
      and alpha-lactose monohydrate using near-infrared spectroscopy.
AB  - The purpose of this study was to investigate the energetic state of water in
      silicified microcrystalline cellulose (SMCC) and alpha-lactose monohydrate wet
      masses using near-infrared (NIR) spectroscopy. The applicability of NIR
      spectroscopy to studying pharmaceutical wet masses at a wide moisture range was
      evaluated in comparison with mixer torque rheometry (MTR). With increasing
      moisture content changes in the physical properties of the samples resulted in an
      apparent increase in log (1/R) throughout the whole spectrum. The upward
      displacement of baseline and the relative height of water bands were greatest
      with materials that had a poor liquid-retention capacity. In the case of SMCC and
      1:1 mixture of SMCC and alpha-lactose monohydrate, the height of the baseline
      corrected water bands increased linearly at low moisture contents, thereafter
      achieving a plateau stage. According to the MTR results, the plateau stage of the
      band heights indicated a capillary state of liquid saturation. The second
      derivative spectrum was capable of distinguishing monohydrate, absorbed, and
      adsorbed water, which overlapped in the absorbance spectrum. When water was
      absorbed to the internal structure of the material (SMCC), the water bands were
      first seen at higher wavelengths, then followed by a shift to lower wavelengths.
      When water was only adsorbed onto the surface of the particles (glass ballotini),
      the water bands were seen directly in the region of bulk water.

PMID- 11247269
TI  - A novel method for measuring gel strength of controlled release hydrogel tablets
      using a cone/plate rheometer.
AB  - A novel method for measuring gel strength of hydrogel controlled release (CR)
      tablets is presented. CR tablets containing hydroxypropyl methylcellulose (HPMC)
      were fixed to a glass plate, placed in a dissolution apparatus, and subjected to
      dissolution conditions corresponding to 50% drug release. Tablets were then
      removed from the dissolution apparatus without disturbing the swollen (gel)
      layer. Tablet gel strength (gamma) was determined by shearing the external gelled
      layer of the tablet by a cone/plate rheometer recording E, energy/volume, as a
      function of rotational speed of the cone, RPM. The RPM is increased to the point
      of "Shear Failure," RPMsf, i.e., until there is no further increase in E. Plots
      of E vs. RPM were fit to a bi-exponential equation, where epsilon is the zero RPM
      intercept of the plot. gamma is calculated from gamma = ERPMsf - epsilon. gamma
      is defined as the minimum energy input/unit volume needed to cause shear failure
      of the tablet gel layer. Mean gamma for tablets containing 50% theophylline and
      different ratios of HPMC to Fast Flo lactose were determined. Tablets containing
      30%, 15%, and 8% HPMC K100MP have gamma means of 6600, 4700, and 1500 ergs/cm3,
      and percent relative standard deviations of 9, 13, 33%, respectively. Tablets
      made entirely of HPMC K100MP (no theophylline or lactose) have an gamma of 15,500
      ergs/cm3. gamma values are significantly different (p < 0.0001) between the
      various formulations. gamma values also show a strong inverse correlation with
      the cumulative percent of drug released in vitro. Results obtained demonstrate
      the application of this novel method for measuring gel strength of different CR
      hydrogel tablets and using this strength to characterize drug diffusion in vitro.

PMID- 11247270
TI  - A better dissolution method for ranitidine tablets USP.
AB  - Ranitidine tablets USP showed variable intra- and inter-lab dissolution results.
      In order to ascertain the reason for this behavior, ranitidine tablets USP
      produced by (BIPI) Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, and
      Zantac Tablets (brand of ranitidine USP), Glaxo Inc., Research Triangle, NC, were
      subjected to the compendia (USP) dissolution testing using paddle and basket
      apparatus. Two potencies of tablets 150 mg and 300 mg were tested. Comparison of
      BIPI tablets and matching Zantac tablets indicated that both brands of ranitidine
      tablets USP had similar dissolution behavior. When the basket apparatus was
      substituted for the paddle apparatus the overall rate and extent of tablet
      dissolution increased, while the individual tablet variability decreased. BIPI
      150 mg tablets using the basket apparatus, but at reduced rotational speed of 30
      rpm, showed increase in rate and extent of drug dissolved, with less individual
      tablet variability compared to the paddle apparatus at 50 rpm. The 300 mg tablet
      (30 rpm/basket apparatus) had an initial slower rate, but then rapidly equaled
      the paddle apparatus dissolution results, and had less individual tablet
      variability. Paddle apparatus tablet sinkers were used to prevent tablets from
      sticking to the bottom of the dissolution vessel. Overall dissolution for all
      tablets with sinkers showed a trend which was more rapid and complete than
      tablets without sinkers. Results showed that dissolution artifacts for ranitidine
      tablets could be reduced by the use of baskets or tablet sinkers.

PMID- 11247271
TI  - Assessment of the extrudability of three different mixtures of saturated
      polyglycolysed glycerides by determination of the "specific work of extrusion"
      and by capillary rheometry.
AB  - PURPOSE: Assessment of the extrudability of mixtures of saturated polyglycolysed
      glycerides used as carriers for poorly soluble drugs. METHODS: Three different
      mixtures of saturated polyglycolysed glycerides were extruded in a ram extruder
      at different rates and using different dies. The force applied to the ram and its
      displacement were recorded and used to determine the "specific work of extrusion"
      and pursuit rheometric determinations, according to the Bagley's approach.
      RESULTS: As the melting range of the mixtures, or the length of the dies
      increased, the higher the "specific work of extrusion" observed. From the
      rheometric analysis, viscoelastic properties were identified and decomposed into
      plastic and elastic components. The elastic component contributed more to the
      total pressure loss, and for the majority of the cases, was higher than the
      plastic component. From the Bagley plot it was possible to calculate the wall
      shear stress (sigma w), that increased with the melting range of the materials
      and the shear rate applied (gamma). The viscosity (eta) decreased as the shear
      rate increased, reflecting a non-Newtonian behavior of the materials. Finally,
      materials showing lower viscosities required less work to produce the extrudates.
      CONCLUSIONS: This study has (a) shown the possibility of preparing extrudates
      from different mixtures of polyglycolysed glycerides alone in a non-aqueous
      environment, (b) demonstrated the usefulness of the "specific work of extrusion,"
      and (c) revealed through the rheometric studies the viscoelastic nature of the
      materials quantifying the contribution of the elastic and the plastic components
      for the total pressure loss.

PMID- 11247272
TI  - A comparison of reflectance and transmittance near-infrared spectroscopic
      techniques in determining drug content in intact tablets.
AB  - Drug contents of intact tablets were determined using non-destructive near
      infrared (NIR) reflectance and transmittance spectroscopic techniques. Tablets
      were compressed from blends of Avicel PH-101 and 0.5% w/w magnesium stearate with
      varying concentrations of anhydrous theophylline (0, 1, 2, 5, 10, 20 and 40%
      w/w). Ten tablets from each drug content batch were randomly selected for
      spectral analysis. Both reflectance and transmittance NIR spectra were obtained
      from these intact tablets. Actual drug contents of the tablets were then
      ascertained using a UV-spectrophotometer at 268 nm. Multiple linear regression
      (MLR) models at 1116 nm and partial least squares (PLS) calibration models were
      generated from the second derivative spectral data of the tablets in order to
      predict drug contents of intact tablets. Both the reflectance and the
      transmittance techniques were able to predict the drug contents in intact tablets
      over a wide range. However, a comparison of the results of the study indicated
      that the lowest percent errors of prediction were provided by the PLS calibration
      models generated from spectral data obtained using the transmittance technique.

PMID- 11247274
TI  - Evaluation of the functional equivalence of crospovidone NF from different
      sources. I. Physical characterization.
AB  - In the past two decades, three categories of newer disintegrants have come into
      widespread use. These substances are a synthetic polymer (crospovidone),
      chemically modified starch (sodium starch glycolate) and cellulose
      (croscarmellose sodium). Multiple suppliers are now available for each category.
      Current NF monographs do not provide tests which reflect on their functionality
      and one cannot assume reliable performance of disintegrants from different
      sources meeting NF standards. The objective of this study was to identify
      differences in physical properties thought to be related to functionality among
      crospovidones from multiple sources. Physical properties examined included
      particle size and distribution, surface area, porosity and surface morphology.
      Disintegration and dissolution were performed on a model tablet formulation using
      either an insoluble or a soluble filler. Substantial differences in particle size
      and distribution, surface area, porosity and surface morphology were observed
      which correlated with differences in disintegration time and dissolution rate of
      the model drug from an insoluble tablet core. None of the differences in physical
      properties resulted in any differences in the disintegration or dissolution of
      the model drug from a soluble tablet core.

PMID- 11247273
TI  - The antioxidant system beta-D(+) glucose-glucose oxidase-catalase: tests for
      pyrogenicity and antigenicity.
AB  - PURPOSE: beta-D(+) glucose-glucose oxidase (E.C.# 1.1.3.4)-catalase (E.C.#
      1.11.1.6) (GO-CAT) is being investigated as a new antioxidant system for use in
      pharmaceutical solutions. This study reports the results of tests for
      pyrogenicity and antigenicity of GO-CAT derived from Aspergillus niger when used
      parenterally in autoclaved preparations. METHODS: The Limulus amebocyte lysate
      (LAL) method was used to test the pyrogenicity of native GO-CAT.
      Pyrogenicity/antigenicity was evaluated in vivo by injecting autoclaved GO-CAT
      into New Zealand white rabbits. Antigenicity was also evaluated by Ouchterlony
      and Western blotting. RESULTS: None of the native GO-CAT concentrations tested
      (up to 30.83 u/ml) produced a positive gel clot in the LAL test, thereby
      suggesting its non-pyrogenicity. The rabbits, which received seven injections of
      autoclaved GO-CAT over a period of eleven weeks, remained healthy during and
      after the GO-CAT injections. All Ouchterlony and Western blot assays using sera
      from rabbits injected with autoclaved GO-CAT were negative. Furthermore,
      autoclaved GO-CAT could not be detected in Ouchterlony assays using a mouse
      monoclonal antibody (GO40 mAb) to native A. niger glucose oxidase. Control
      samples containing native GO-CAT produced an antigen-antibody complex reaction in
      Ouchterlony assays against the GO40 mAb. Antigen-antibody complexes could be
      detected by non-denaturing PAGE in samples containing native GO-CAT/GO40 and
      boiled GO-CAT/GO40, but not in samples containing autoclaved GO-CAT/GO40. These
      results indicate autoclaved GO-CAT is neither pyrogenic nor antigenic.
      CONCLUSIONS: Based on these results, there is potential for the use of beta-D(+)
      glucose-glucose oxidase-catalase as an antioxidant system in pharmaceutical
      solutions, particularly in terminally autoclaved aqueous formulations for
      parenteral use.

PMID- 11247275
TI  - Influence of curing on the adhesive and thermomechanical properties of an applied
      acrylic polymer.
AB  - The objective of the current study was to investigate the relationship between
      polymer adhesion and post-coating thermal treatment. A novel adhesion technique
      was used to quantify the adhesive properties of applied acrylic films.
      Differential scanning calorimetry was used to determine the glass transition
      temperature of the applied polymer. Post-coating thermal treatment, or curing,
      was found to significantly influence the adhesive and thermomechanical properties
      of the applied film coating. Adhesion of triethyl citrate-plasticized films to
      tablets increased during storage at elevated temperatures, equilibrating within
      four hours. The glass transition temperature of the applied triethyl citrate
      plasticized coatings also increased during curing. Equilibration of polymer
      properties was found to be dependent on the hydrophobicity of the plasticizer
      incorporated into the coating formulation, with longer curing times required for
      films containing the hydrophobic plasticizer tributyl citrate. The curing
      temperature was shown to influence polymer properties, with stronger film-tablet
      adhesion and higher glass transition temperatures resulting when the coated
      tablets were stored at higher temperatures. Substrate hydrophobicity was also
      found to influence the curing process, suggesting that the mechanisms involved in
      film formation and polymer-substrate adhesion may contribute to the internal
      stresses within the film.

PMID- 11247276
TI  - Time dependence of elastic recovery for characterization of tableting materials.
AB  - The purpose of this study was to complete information on elastic recovery during
      a compression cycle by measuring the expansion of the tablet after ejection, and
      thus, to measure the whole recovery process, which means the time dependency of
      elastic recovery. Two methods were applied: manual measurement by a micrometer
      screw, and a continuous measurement by thermomechanical analysis, always at a
      constant temperature and humidity. Elastic recovery of the tablet continued after
      ejection from the die, and the amount of expansion was different for the
      tableting materials used. The results showed that expansion continued for most of
      the materials over several days, until a steady state of the tablet and its
      physical properties was reached. The extent and the profiles of the elastic
      recovery curves were different for the tableting materials dicalcium phosphate
      dihydrate, carrageenan, microcrystalline cellulose, cellulose acetate,
      hydroxypropyl methylcellulose and theophylline monohydrate. There were slight
      differences between both the methods used. The profiles of the materials could be
      related to some properties of the materials.

PMID- 11247277
TI  - Interpolymer complexation. II. Entrapment of ibuprofen by in-situ complexation
      between polyvinyl acetate phthalate (PVAP) and polyvinylpyrrolidone (PVP) and
      development of a chewable tablet formulation.
AB  - A new method involving in situ complexation between polyvinyl acetate phthalate
      (PVAP) and polyvinylpyrrolidone (PVP) has been developed for the entrapment of
      ibuprofen, a bitter tasting anti-inflammatory drug. The procedure involved
      dissolving ibuprofen in a thoroughly mixed aqueous alkaline solution of PVAP and
      PVP, and subsequently slowly adjusting the pH of the solution to 1 with dilute
      HCl. The yield of the entrapped product, and the percent entrapment of ibuprofen,
      were 85-90%, and 90-98%, respectively. The PVAP-PVP entrapped granules showed no
      bitter taste due to ibuprofen. The chewable tablets, prepared by mixing the
      granules with a cherry-flavored directly compressible tableting excipient,
      exhibited a release of less than 2% of ibuprofen in pH 1.2 buffer over a period
      of three hours. In pH 7.4, 100% of ibuprofen was released in six hours. The
      results presented show that in situ complexation between PVAP and PVP may be
      useful to produce palatable ibuprofen granules suitable for use in the
      development of chewable tablets.

PMID- 11247278
TI  - Ultrasonic nebulization system for respiratory drug delivery.
AB  - An ultrasonic spray system was tested for the production of aerosols for ultimate
      use in the respiratory delivery of drug to animals. A Sono-Tek ultrasonic spray
      system was mounted on top of a baffle to entrain aerosol particles within the
      carrier gas. Solvent was removed from the aerosol cloud by passing the droplets
      through drying columns composed of either charcoal or silica. The efficiency of
      removing ethanol and water were determined by measuring the outflow
      concentrations. Sodium fluorescein and sodium cromolyn dissolved in water were
      tested, and the effect of the liquid flow rate and drug concentration entering
      the atomizer on the output, and particle size distribution, were determined by
      the filter capture method, and by cascade impactor, respectively. Similar studies
      were conducted with budesonide and indomethacin dissolved in ethanol. The
      theoretical count median size distribution was calculated and compared with the
      experimental values calculated from the observed mass median aerodynamic
      diameter. The output rate expressed as the mass of aerosol collected in unit time
      increased nearly proportionately with the liquid flow rate (0.18-0.7 ml/min) and
      with the concentration of drug (0.19-12 mg/ml) entering the nebulizer. The mean
      particle size increased with solute concentration, but not by liquid flow rate.
      The calculated count median diameters were dependent on the type of solvent, but
      were independent of solute. At the high dose of cromolyn, there was very good
      agreement between the theoretical and observed. At lower doses, the observed size
      was larger than predicted, which was also true for the ethanol soluble solutes.
      The system has the potential of providing a wide range of dose levels for testing
      of drug delivery to animals including high doses with a controlled and relatively
      narrow particle size distribution.

PMID- 11247279
TI  - Release of furosemide from multiple-unit and single-unit preparations containing
      different viscosity grades of sodium alginate.
AB  - The release characteristics and the effect of viscosity of sodium alginate on the
      release rate of furosemide (a rather poorly soluble drug) from hard gelatin
      capsules (single-unit), and minitablets (multiple-unit) filled in hard gelatin
      capsules, were evaluated. Swelling and erosion experiments showed a different
      behavior for each viscosity grade. Polymer characteristics influenced
      significantly the release of the drug from the preparations prepared and tested.
      The results indicate that erosion plays a significant role, accelerates release
      rate and shortens duration of drug release. Low viscosity formulations exhibited
      a greater erosion, and drug release was completed in 4 hours. Medium viscosity
      formulations showed intermediate erosion, while high viscosity formulations
      exhibited less erosion, and drug release was completed in 8 hours. The
      minitablets always displayed lower release and dissolution efficiency values than
      the capsules, and as the viscosity increased, the difference of dissolution
      efficiency between the two formulations increased accordingly. The results
      further indicated that the multiple-unit system demonstrated a more pronounced
      sustained effect than the single-unit, and therefore, it is a more suitable
      preparation for sustained release delivery of poorly soluble drugs. Analysis of
      release data indicate a rather zero-order release mechanism, which may be
      attributed mainly to swelling and an erosion/dissolution process.

PMID- 11247280
TI  - Effects of light intensity, n-alcohols, water-soluble colorants, and solution
      viscosity on photoisomerization of sorivudine.
AB  - Effects of various factors, such as light intensity, polarizability of n-alcohol
      solvents, addition of colorants, and viscosity of solutions on the kinetics of
      the photoisomerization of therapeutically effective E-isomer of sorivudine to its
      less effective Z-isomer were studied. Solutions of known concentrations of E
      isomer or Z-isomer in water or in a series of n-alcohols were directly exposed to
      ultraviolet (UV) A light, or visible light of 400 or 900 foot candles (fc). E
      isomer solutions containing various colorants at 1% w/v, or in a series of
      poloxamer solutions of different viscosities, were also exposed to 400 or 900 fc
      light. Using the stability-indicating HPLC assay, which showed mass-balance
      between the starting isomer and the converting isomer, the kinetics of
      photoisomerization were monitored. The photoisomerization reaction, which takes
      place on the vinyl side chain, was found to be a first-order reversible reaction.
      In water, the rate of conversion of E-isomer to Z-isomer was faster than that of
      Z-isomer to E-isomer, since, E-isomer with higher extinction coefficient absorbed
      substantially more light than Z-isomer. The rate of photoisomerization increased
      with the intensity of the visible light and was very rapid in the presence of UV
      A light (300 to 400 nm), which is to be expected based on the 239 nm and 283 nm
      absorption maxima of sorivudine. Addition of water-soluble colorants retarded the
      photoisomerization process significantly, especially as the maximum absorption
      wavelengths (lambda max) of the colorants approached the UV region. The rate of
      photoisomerization increased with increasing polarizability (alpha s) of the n
      alcohol solvents. Polarizable solvents such as alcohols could compensate for the
      electron density built up in the excited state, and thus facilitated the
      photoisomerization process. The rate of photoisomerization decreased as the
      viscosity of solution increased. This may be attributed to the fact that the
      twisting of the C=C bond in the excited state can be inhibited by the friction
      imposed by the viscous medium.

PMID- 11247281
TI  - [Social psychological factors of interest in lay personality theories: why is ABO
      blood-typing popular?].
AB  - We hypothesized that one of the reasons that not a few Japanese are interested in
      lay personality theories of ABO blood-typing and similar unsupported beliefs on
      human nature, was unsatisfied needs of having clear collective and personal
      identities. To test the hypothesis, we asked 149 married women, 34 to 62 years of
      age, to describe themselves as in self introduction to strangers, and then
      separately indicate the degree of interest in lay personality theories. We then
      counted the number of references to personal/private aspects (an index of
      personal identity) and the number to social groups whose membership was known to
      be exclusive and limited (an index of collective one). Results showed that those
      who were high on both indices were less interested in lay theories than those low
      on one or both of personal and collective indices.

PMID- 11247282
TI  - [The effects of long-term husband absence on wives' stress: a cross-sectional and
      longitudinal study].
AB  - The effects of long-term husband absence on wives' stress reaction and child-care
      anxiety were examined in a cross-sectional and longitudinal study. Women whose
      husband was transferred together with his family (taido-funin, N = 180) and those
      without his (tanshin-funin, N = 229) completed a questionnaire of their own
      stress reaction and child-care anxiety. Five years later, they were again asked
      to complete the same questionnaire. Of those who participated in the second
      survey, husbands of 25 wives were still away as tanshin-funin, those of 51
      returned and rejoined his family, and 37 families remained as taido-funin.
      Results of ANOVAs were as follows: Women whose husband continued tanshin-funin
      reported more stress reaction than those whose husband returned. Expectation of
      long-term absence was more harmful than that of brief absence. Expectation of
      long-term absence was more harmful than actual long-term absence. Expectation as
      well as actual experience of long-term absence had worse effects on wives who had
      older children, e.g., of college age, than those with younger ones. Finally, no
      effect of prolonged husband absence was found on child-care anxiety.

PMID- 11247283
TI  - [Construction of scales to measure thematic tendencies of paranoid ideation].
AB  - In order to measure thematic tendencies of paranoid ideation in non-clinical
      samples, Delusional Ideation Checklist (DICL) was developed. A wide range of
      items indicating themes of delusion were collected. From the results of factor
      analysis on the data of 308 college students, eight scales were constructed. They
      were: alienation, belittlement, persecution, other-harming, guardedness, self
      conceit, favoredness, and other-manipulation. These scales could be classified in
      terms of emotion: positive versus negative, and direction: self versus others,
      and could deal with themes of paranoid ideation in a comprehensive and systematic
      way. Alpha coefficients of the scales were between .66 and .87, and test-retest
      reliability between .49 and .71. To examine content validity, ten psychiatrists
      were asked to rate diagnostic importance for each scale item. Six scales were
      rated as significantly more important in the diagnosis of paranoid schizophrenia
      than that of anxiety neurosis. Current data revealed that ordinary students
      experienced delusional ideation more frequently than psychiatrists would expect.

PMID- 11247284
TI  - [The influence of verbal encoding on the memory of visual information].
AB  - The previous research which investigated the effect of verbal encoding on the
      memory of visual information has yielded contradictory results: facilitation and
      inhibition of performance by verbal encoding. However, it has not been elucidated
      why and how these conflicting results were brought about. The main purpose of
      this study is to show that verbal encoding not only facilitates but also impairs
      performance by taking task demand and characteristics of visual representations
      into account. Another purpose is to investigate how verbal encoding would
      influence the memory of color information, which is irrelevant for the memory
      task. In Experiment 1, the results showed that verbal encoding could have two
      opposite effects in the same task. In Experiment 2, the results showed that the
      effect of verbal encoding on the memory of color would differ from that on the
      memory of the shapes of pictures.

PMID- 11247285
TI  - [Does negative priming occur by rotated characters?].
AB  - We conducted three experiments in order to investigate the effect of stimulus
      orientation on negative priming (NP). Using the picture naming task, Murray
      (1995) reported the occurrence of semantic NP by rotated distractors. As the
      rotation of picture stimuli seems to have little effect to reduce distractor
      interference, in the present study we used the character (katakana)
      identification task to ensure the effect of stimulus rotation. When the
      distractors were rotated (180 degrees), no NP was observed whether the targets
      were upright (Experiment 1) or rotated (Experiment 2). On the other hand,
      significant NP was observed when the distractors were upright and the targets
      were rotated (Experiment 3). These results suggest that the inhibitory mechanism
      of attention may not operate on the rotated distractor characters.

PMID- 11247286
TI  - [Effects of impression of faces on recognition of changes in face arrays:
      addition versus deletion].
AB  - A study was conducted examine whether the asymmetric confusability effect was
      generalized to an array of face photographs, and furthermore to investigate how
      the impression of faces affected the recognition of addition and deletion of the
      faces. In a preliminary investigation, 27 subjects rated the impression of 83
      face photographs, and the photographs to be used in the present study were chosen
      on the basis of the impression scores. In the study, 40 subjects saw 14
      photographs consisted of three or four faces and took a recognition test of
      unchanged photographs and changed photographs with a specific face added or
      deleted. The data showed that (a) the addition superiority was not found in the
      recognition of changes in face arrays; (b) the impression of faces differentially
      affected the recognition of addition and deletion changes in face arrays. These
      results suggest that the mechanism underlying the recognition of the deletion of
      a face may be different from that of addition.

PMID- 11247287
TI  - [Is more really up?: experimental evidence for orientational metaphor].
AB  - The purpose of this study was to provide experimental evidence for orientational
      metaphors based on the UP-DOWN image schema. Two experiments were conducted to
      examine the effects of the image schema on the picture-word comparison tasks. In
      the experiments, subjects were required to judge if the location of kanji-target
      matched the word printed at the center of a reference square. Under the condition
      in which the location and the metaphorical orientation of the kanji-target
      disagree, it took longer time for judgment. These results are interpreted in
      terms of accessibility and availability of the image schema.

PMID- 11247288
TI  - [Rethinking the Sapir-Whorf hypothesis: role of language in shaping thought].
AB  - Traditionally, the issue of the relationship between language and thought has
      been framed as the Sapir-Whorf hypothesis, in which crosslinguistic-crosscultural
      universality or diversity of thought has been the center of the debate. The long
      lasting debate revolving around the hypothesis has not yielded a clear,
      satisfactory conclusion. This unsatisfactory result seems to be largely
      attributed to the fact that (a) the term "thought" has been so vaguely defined,
      and that (b) the interpretation of the Sapir-Whorf hypothesis itself has been
      quite diverse among researchers. In this paper, I argue that the question we
      should ask is not whether thought is universal or different across different
      language groups. Instead, we should ask more specific (and realistic) questions,
      taking it for granted that our thought is constrained by innate language
      independent cognitive faculties but at the same time a large part of our thought
      is shaped by language. The questions we should ask are: in what cognitive domains
      (e.g., spatial cognition, ontological knowledge, categorization of natural
      objects etc.), at what specific level (e.g., perception, memory, knowledge
      representation, on-line information processing) and in what degree (a) our
      thought is influenced by the specific structure of the given language (or is
      immune to it) and (b) our thought is shaped by language learning (or constrained
      by language-independent innate cognitive structure). In order to reevaluate the
      Sapir-Whorf hypothesis in this new perspective, I reviewed literature mainly
      focusing on three distinctive cognitive domains: ontological knowledge with
      respect to individuation, categorization of natural objects, and spatial
      cognition.

PMID- 11247289
TI  - [Predictive factors of the mortality of digestive hemorrhage caused by esophageal
      varices in elderly patients].
AB  - Complications of liver cirrhosis are increasingly frequent in elderly patients
      due to increased life expectancy and better management of cirrhotic patients.
      However, the influence of this condition on the evolution of variceal bleeding
      has not been well established. The aim of the present study was to determine the
      characteristics of esophagogastric variceal bleeding in elderly patients and the
      possible influence of advanced age on hemorrhage-related mortality. We analyzed
      321 episodes of variceal bleeding in 227 cirrhotic patients. One hundred and
      thirteen (35.2%) episodes occurred in patients older than 65 years. No
      differences were found among patients older or younger than this age in terms of
      bleeding characteristics or Child-Pugh score. Patients older than 65 years more
      frequently presented serious associated diseases, hepatocellular carcinoma and
      hepatic encephalopathy during the episode (52.7% vs. 14%, p < 0.001; 19.7% vs.
      8.7%, p = 0.01 and 17.4% vs. 10%, p = 0.09 respectively). Although hemorrhage
      related mortality was higher in elderly patients (23.2% vs. 13.5%, p = 0.04),
      only the Child-Pugh score, definitive hemostasis, hepatocellular carcinoma and
      the development of encephalopathy or bacterial infection were independent
      predictive factors of mortality. A considerable proportion of the patients with
      esophagogastric variceal bleeding were older than 65 years. Advanced age does not
      independently influence mortality due to variceal bleeding.

PMID- 11247290
TI  - [Basal concentrations of gastrin and pepsinogen I and II in gastric ulcer:
      influence of Helicobacter pylori infection and usefulness in the control of the
      eradication].
AB  - AIM: To study the influence of Helicobacter pylori eradication on basal gastrin
      and pepsinogen I and II levels in patients with gastric ulcer over a 1-year
      follow-up period, and to assess the usefulness of these values in confirming H.
      pylori eradication after treatment. METHODS: Fifty-six patients with gastric
      ulcer and H. pylori infection were prospectively studied. At the beginning of the
      study, endoscopy with biopsies for histologic examination and urease testing was
      carried out, as were 13C-urea breath test and blood samples for determination of
      gastrin and pepsinogen I and II values by radioimmunoassay and serology.
      Histologic study, 13C-urea breath test and laboratory determinations were
      repeated at months 1, 6 and 12 after completion of eradication treatment.
      RESULTS: H. pylori infection was eradicated in 82.1% of patients. In patients
      with successful H. pylori eradication, the initial mean gastrin value was 75.5 +/
      39.1 pg/ml, while at 1 month after treatment this value decreased to 49.2 +/- 21
      pg/ml (p < 0.0001). No further reductions were noted. Initial pepsinogen I and II
      values were 104 +/- 58 and 15.8 +/- 10 ng/ml, respectively, whereas at month 1
      after treatment these values were 77 +/- 42 and 7.3 +/- 4 ng/ml, respectively (p
      < 0.0001) and were 72 +/- 41 and 6.7 +/- 3 ng/ml respectively at month 6 (p <
      0.01); no further variations were observed thereafter. The area under the ROC
      curve which reveals eradication through reductions in hormonal values was 0.70
      for gastrin, 0.78 for pepsinogen I, 0.93 for pepsinogen II and 0.92 for the
      pepsinogen I/II ratio. At months 6 and 12 after treatment completion, differences
      in mean gastrin and pepsinogen I and II values between the patients with normal
      histologic findings and those with chronic gastritis were significant (p < 0.05).
      CONCLUSIONS: a) H. pylori eradication is associated with an early fall in basal
      gastrin values and a progressive decrease in basal pepsinogen I and II values. b)
      In patients with gastric ulcer, determination of the decrease in basal pepsinogen
      II levels is a useful and early non-invasive method for confirming eradication.
      c) Determination of gastrin and pepsinogen I and II values may be useful for
      assessing improvement in gastritis 6 months after treatment completion.

PMID- 11247291
TI  - [Krukenberg tumor secondary to gastric carcinoma in a woman in her eighth month
      of pregnancy].
AB  - The association of gastric cancer and pregnancy is rare. The cases reported by
      non-Japanese authors are unusual. Tumors tend to be in advanced stage when
      diagnosed since the symptoms of gastric cancer are easily presumed to be
      secondary to those of normal pregnancy. We report the case of a 43-year-old
      female with gastric carcinoma presenting as a Krukenberg's tumor in the eighth
      month of gestation. A healthy child was born and after delivery, partial
      gastrectomy was performed and adjuvant chemotherapy was administered. The patient
      died 12 months after diagnosis.

PMID- 11247293
TI  - [Pharmacologic and clinical interest of serotonergic receptors of the
      gastrointestinal tract].

PMID- 11247292
TI  - [Polyps of the biliary tract: is their preoperative diagnosis possible?].
AB  - Bile duct polyps are a very uncommon cause of obstructive jaundice. We present
      our experience of three patients diagnosed in the last 10 years. Initial
      presentation usually takes the form of obstructive jaundice associated with
      abdominal pain, which simulates biliary lithiasis. The diagnosis is usually
      surgical. Although in some cases radiological studies and endoscopic retrograde
      cholangiopancreatography (ERCP) may sometimes detect bile duct polyps, exact
      diagnosis before surgery is very unusual. The radiological signs that suggest the
      existence of a bile duct polyp in the ERCP seem to be the presence of repletion
      defects, fixed unilaterally to the biliary conduit, without meniscus and without
      circumferential stenosis of the affected conduit. The most frequently found
      polyps are fibroinflammatory, and less frequently adenomatous.

PMID- 11247294
TI  - [Interventional endoscopic ultrasonography].

PMID- 11247295
TI  - [Azathioprine and cavum carcinoma in a patient with autoimmune hepatitis and
      Crohn's disease].

PMID- 11247296
TI  - [Klippel-Trenaunay syndrome. Another cause of colorectal varices].

PMID- 11247297
TI  - [Brain pathology in atherosclerosis and arterial hypertension: systemic
      approach].

PMID- 11247298
TI  - [The stress phenomenon. Emotional stress and its role in pathology
      (continuation)].

PMID- 11247299
TI  - [Prospects of medicinal use of achievements in genomics: the beginning of era of
      complete genome medical genetics].

PMID- 11247301
TI  - A third specificity-determining site in mu 2 adaptin for sequences upstream of
      Yxx phi sorting motifs.
AB  - Internalization signals of the Yxx phi type (phi = bulky hydrophobic side chain)
      interact with the mu 2 chain of AP-2 adaptors. Internalization activity is
      intolerant of non-conservative substitution of either the tyrosine or the phi
      side chains, which bind to hydrophobic pockets in mu 2 adaptin in a conformation
      described as 'a two pinned plug into a socket'. P-selectin, a type I
      transmembrane protein, contains the Yxx phi-like sequence YGVF in its cytoplasmic
      domain, but substitution of either the tyrosine or phenylalanine with alanine in
      the full-length protein causes only small changes in the rate of endocytosis. It
      is shown here that the sequence YGVF contained within a peptide corresponding to
      the 17 COOH-terminal amino acids of P-selectin binds to mu 2 adaptin in the same
      fashion previously seen for other Yxx phi motifs. In addition, the P-selectin
      peptide binds to a third hydrophobic pocket in mu 2 adaptin through a leucine at
      position Y-3 in the peptide. This structure suggests that some sequences can
      function as a 'three pinned plug', in which internalization activity is not
      critically dependent on any one of the three interacting side chains.

PMID- 11247302
TI  - Disabled-2 colocalizes with the LDLR in clathrin-coated pits and interacts with
      AP-2.
AB  - Disabled-2 (Dab2) is a widely expressed relative of Disabled-1, a neuron-specific
      signal-transduction protein that binds to and receives signals from members of
      the low-density lipoprotein receptor (LDLR) family. Members of the LDLR family
      internalize through clathrin-coated pits and vesicles to endosomes, from where
      they return to the cell surface through the secretory pathway. In this study, we
      show that the Dab2 phosphotyrosine-binding domain binds peptides containing the
      sequence FXN-PXY. This core sequence is found in the intracellular domains of
      LDLR family members and is important for receptor internalization. Dab2
      transiently colocalizes with the LDLR in clathrin-coated pits, but is absent from
      endosomes and lysosomes. Dab2 is alternatively spliced and its localization
      depends on a region of the protein that contains two DPF motifs that are present
      in the p96 Dab2 protein and absent in the p67 splice variant. This region is
      sufficient to confer Dab2 binding to the alpha-adaptin subunit of the clathrin
      adaptor protein, AP-2. Overexpression of p96 but not of p67 Dab2 disrupts the
      localization of AP-2. These findings suggest that in addition to previously
      reported signal-transduction functions, Dab2 could also act as an adaptor protein
      that may regulate protein trafficking.

PMID- 11247303
TI  - Antigen loading of MHC class I molecules in the endocytic tract.
AB  - Major histocompatibility complex (MHC) class I molecules bind antigenic peptides
      that are translocated from the cytosol into the endoplasmic reticulum by the
      transporter associated with antigen processing. MHC class I loading independent
      of this transporter also exists and involves peptides derived from exogenously
      acquired antigens. Thus far, a detailed characterization of the intracellular
      compartments involved in this pathway is lacking. In the present study, we have
      used the model system in which peptides derived from measles virus protein F are
      presented to cytotoxic T cells by B-lymphoblastoid cells that lack the peptide
      transporter. Inhibition of T cell activation by the lysosomotropic drug
      ammoniumchloride indicated that endocytic compartments were involved in the class
      I presentation of this antigen. Using immunoelectron microscopy, we demonstrate
      that class I molecules and virus protein F co-localized in multivesicular
      endosomes and lysosomes. Surprisingly, these compartments expressed high levels
      of class II molecules, and further characterization identified them as MHC class
      II compartments. In addition, we show that class I molecules co-localized with
      class II molecules on purified exosomes, the internal vesicles of multivesicular
      endosomes that are secreted upon fusion of these endosomes with the plasma
      membrane. Finally, dendritic cells, crucial for the induction of primary immune
      responses, also displayed class I in endosomes and on exosomes.

PMID- 11247304
TI  - Energetics of clathrin basket assembly.
AB  - A minimal thermodynamic model is used to study the in vitro equilibrium assembly
      of reconstituted clathrin baskets. The model contains parameters accounting for
      i) the combined bending and flexing rigidities of triskelion legs and hubs, ii)
      the intrinsic curvature of an isolated triskelion, and iii) the free energy
      changes associated with interactions between legs of neighboring triskelions.
      Analytical expressions for basket size distributions are derived, and published
      size distribution data (Zaremba S, Keen JH. J Cell Biol 1983;97: 1339-1347) are
      then used to provide estimates for net total basket assembly energies. Results
      suggest that energies involved in adding triskelions to partially formed clathrin
      lattices are small (of the order of kBT), in accord with the notion that lattice
      remodeling during basket formation occurs as a result of thermodynamic
      fluctuations. In addition, analysis of data showing the effects of assembly
      proteins (APs) on basket size indicates that the binding of APs increases the
      intrinsic curvature of an elemental triskelial subunit, the stabilizing energy of
      leg interactions, and the effective leg/hub rigidity. Values of effective
      triskelial rigidity determined in this investigation are similar to those
      estimated by previous analysis of shape fluctuations of isolated triskelia.

PMID- 11247305
TI  - Neurotoxic traffic: uncovering the mechanics of amyloid production in Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) is thought by many to result from the accumulation of
      the neurotoxic amyloid-beta (A beta) peptide in brain parenchyma. The process by
      which A beta is proteolytically derived from the larger amyloid precursor protein
      (APP) has been the focus of much attention in the AD research field over the past
      decade. Recently, several of the proteins directly involved in the generation of
      A beta have been identified and characterized providing a number of viable
      therapeutic targets for the treatment of AD. However, the cellular mechanisms by
      which these proteins interact in the proteolytic processing of APP have not been
      well defined, nor are they readily apparent when one considers what is known
      about the intracellular localization and trafficking of the various participants.
      This article will review the underlying cell biology of A beta production and
      discuss the mechanistic options for APP processing given the current knowledge of
      the proteases involved.

PMID- 11247306
TI  - Prominin: a story of cholesterol, plasma membrane protrusions and human
      pathology.
AB  - Prominin is the first identified member of a novel family of polytopic membrane
      proteins conserved throughout the animal kingdom. It has an unusual membrane
      topology, containing five transmembrane domains and two large glycosylated
      extracellular loops. In mammals, prominin is expressed in various embryonic and
      adult epithelial cells, as well as in nonepithelial cells, such as hematopoietic
      stem cells. At the subcellular level, prominin is selectively localized in
      microvilli and other plasma membrane protrusions, irrespective of cell type. At
      the molecular level, prominin specifically interacts with membrane cholesterol
      and is a marker of a novel type of cholesterol-based lipid 'raft'. A frameshift
      mutation in the human prominin gene, which results in a truncated protein that is
      no longer transported to the cell surface, is associated with retinal
      degeneration. Given that prominin is concentrated in the plasma membrane
      evaginations at the base of the outer segment of rod photoreceptor cells, which
      are essential precursor structures in the biogenesis of photoreceptive disks, it
      is proposed that prominin has a role in the generation of plasma membrane
      protrusions, their lipid composition and organization and their membrane-to
      membrane interactions.

PMID- 11247307
TI  - The roles of claudin superfamily proteins in paracellular transport.
AB  - The claudin superfamily consists of at least 18 homologous proteins in humans.
      These proteins are important structural and functional components of tight
      junctions in paracellular transport. Complexed with two other integral
      transmembrane proteins, occludin and junctional adhesion molecule, claudins are
      located in both epithelial and endothelial cells in all tight junction-bearing
      tissues. Claudins interact directly with tight junction-specific, membrane
      associated guanylate kinase homologues, ZO-1, ZO-2, and ZO-3, and indirectly with
      AF-6 and the myosin-binding molecule cingulin. These protein-protein interactions
      promote scaffolding of the tight junction transmembrane proteins and provide a
      link to the actin cytoskeleton for transducing regulatory signals to and from
      tight junctions. The distinct permeability properties observed in different
      epithelia and endothelia seemingly result from the restricted tissue expression,
      variability of the homopolymer and heteropolymer assembly, regulated
      transcription and translation, and the subcellular localization of claudin family
      proteins. Defects in claudins are causatively associated with a variety of human
      diseases, demonstrating that claudins play important roles in human physiology.
      In conditions where the cell adhesion function contributed by tight junctions is
      essential, such as in altered paracellular transport, in proliferative diseases,
      and during morphogenesis, the claudin superfamily of homologous proteins provides
      the molecular basis for the uniqueness of tight junctions and emerges as a new
      target for intervention.

PMID- 11247308
TI  - Strategies for prokaryotic expression of eukaryotic membrane proteins.
AB  - High-level heterologous expression of integral membrane proteins at full-length
      is a useful tool for their structural and functional characterization. Here,
      systems that have previously been used for efficient bacterial expression of
      eukaryotic membrane proteins are reviewed and novel vectors consisting of a
      modular fusion moiety based on nuclease A from Staphylococcus aureus are
      presented.

PMID- 11247310
TI  - Raynaud's phenomenon is linked to unopposed estrogen replacement therapy in
      postmenopausal women.

PMID- 11247309
TI  - Is fibromyalgia a generalized reflex sympathetic dystrophy?
AB  - Fibromyalgia and reflex sympathetic dystrophy share defining characteristics,
      namely chronic pain and allodynia, as well as other important clinical features
      such as onset after trauma, female predominance, paresthesias, vasomotor
      instability, response to sympathetic blockade and anxiety/depression. Recent
      research using heart rate variability analysis demonstrated that patients with
      fibromyalgia have changes consistent with relentless circadian sympathetic
      hyperactivity. I propose that fibromyalgia is a sympathetically maintained pain
      syndrome in which ongoing sympathetic hyperactivity sensitises the primary
      nociceptors and induces widespread pain and allodynia.

PMID- 11247311
TI  - A recently recognised chronic inflammatory disease of early onset characterised
      by the triad of rash, central nervous system involvement and arthropathy.
AB  - Chronic Infantile Neurological Cutaneous and Articular (CINCA) syndrome, also
      called Neonatal Onset Multisystemic Inflammatory Disease (NOMID) is characterised
      by the triad of cutaneous rash, chronic meningitis and arthropathy. It is a
      chronic inflammatory illness that starts most often at birth and persists for the
      whole lifespan of the patient. Attempts at therapy have been disappointing. The
      long-term prognosis is poor, with progressive deafness and visual impairment, and
      worsening of the central nervous system manifestations. Some cases of death have
      been reported secondary to infection, vasculitis and amyloidosis. Usually
      observed as sporadic cases, some familial association is recognised.

PMID- 11247312
TI  - Acute carpal tunnel syndrome caused by calcific periarthritis of the wrist.

PMID- 11247313
TI  - Dramatic efficacy of cyclosporine A in macrophage activation syndrome.

PMID- 11247314
TI  - Sacroiliitis as a presenting manifestation of infective endocarditis.

PMID- 11247315
TI  - Serum neurone-specific enolase in the primary antiphospholipid syndrome: a new
      biochemical marker for cerebral vascular involvement?

PMID- 11247316
TI  - Long-term efficacy and toxicity of a combination therapy in rheumatoid arthritis
      patients.

PMID- 11247318
TI  - Unusual overlap of systemic lupus erythematosus and diffuse scleroderma.

PMID- 11247317
TI  - Vasculitis of adnexa, greater omentum and gallbladder as abdominal manifestations
      of cryoglobulinemic vasculitis.

PMID- 11247319
TI  - Influence of cyclic intravenous pamidronate on proinflammatory monocytic cytokine
      profiles and bone density in rheumatoid arthritis treated with low dose
      prednisolone and methotrexate.
AB  - OBJECTIVES: The aim of this work was to evaluate in a randomised double-blind
      prospective study the effect of pamidronate on intracellular monocytic cytokine
      profiles (IL-1, IL-6, TNF-alpha) and bone density in rheumatoid arthritis
      patients. METHODS: Twenty rheumatoid arthritis patients were treated for one year
      with methotrexate and a low dose of prednisolone. Double blind randomisation was
      performed for either i.v. pamidronate (at 3-month intervals) or placebo. The
      effect of pamidronate was evaluated on intracellular cytokine profiles (IL-1, IL
      6, TNF-alpha), disease activity and bone mass measurements. The human monocytic
      cell line THP-1 was used to evaluate in vitro apoptosis by pamidronate. RESULTS:
      Spontaneous production of interleukin-1 beta by patient blood monocytes was lower
      in the pamidronate group and was associated with an increase in bone density of
      the spine after 12 months of therapy. In vitro a dose-related increase in
      pamidronate induced apoptosis was found in THP-1 cells. CONCLUSIONS: This
      prospective double-blind randomised study demonstrated that pamidronate therapy
      resulted in an increase of bone density despite treatment with steroids. This
      rise is associated with a suppression of interleukin-1 beta production in
      monocytes of patients treated with pamidronate. Our in vitro experiments suggest
      that this anti-inflammatory effect could be due to an increase in the apoptosis
      of monocytic cells.

PMID- 11247320
TI  - Dehydroepiandrosterone sulphate serum levels in systemic sclerosis.
AB  - OBJECTIVE: To evaluate in a cohort of women with systemic sclerosis (SSc) the
      dehydroepiandrosterone sulphate (DHEAS) serum levels and their relationship with
      disease severity. METHODS: DHEAS serum concentrations were measured by
      radioimmunoassay in 40 SSc patients and compared with those in 40 controls
      matched for sex and reproductive status. IL-2 sR alpha was evaluated as a disease
      activity index. A preliminary organ/system severity scale proposed by Medsger et
      al. in 1999 was used to evaluate disease severity. RESULTS: Mean serum levels of
      DHEAS in SSc women of childbearing age were significantly lower than in controls
      (0.87 +/- 0.85 microgram/ml versus 2.75 +/- 0.42 micrograms/ml; p < 0.001). On
      the contrary, no difference was found between postmenopausal women and controls.
      A reduction below the 95% confidence limits was found in 10 out of 11 patients of
      childbearing age and in 8 out of 29 postmenopausal women, respectively. In 5 out
      of 11 patients of childbearing age taking steroids for their SSc (< 10 mg/daily)
      DHEAS levels were significantly lower than in patients not taking steroids (p =
      0.01). On the contrary, 16 out of 29 postmenopausal women using steroids had
      lower DHEAS concentrations than in patients not taking steroids, although the
      difference was not statistically significant. There was no statistically
      significant difference in DHEAS levels between patients with diffuse or limited
      SSc, or between those with or without organ system involvement. No correlations
      were found either in pre- and post-menopausal steroid nonusers, or in limited and
      diffuse subsets, between DHEAS levels and age, postmenopausal years, disease
      duration, IL-2 sR alpha, disease organ/system severity scale. CONCLUSION: Our
      data show that, as in other autoimmune diseases, low serum DHEAS is a feature of
      premenopausal SSc patients. More extensive prospective studies are needed to
      define the exact role of DHEAS dysregulation in SSc.

PMID- 11247321
TI  - Interactions between human osteoarthritic chondrocytes and synovial fibroblasts
      in co-culture.
AB  - OBJECTIVE: To imitate the in vivo joint situation and to allow cell interactions,
      a co-culture system of human osteoarthritic chondrocytes and synovial fibroblasts
      from a single joint was established and characterized with or without stimulation
      by IL-1 beta. METHODS: Culture settings included chondrocytes in alginate alone,
      synovial fibroblasts in monolayer alone and a co-culture of both. Proteoglycan
      (PG) synthesis was measured by 35S-incorporation, PG content by a
      dimethylmethylene blue assay, DNA content by a fluorometric assay, and
      prostaglandin-E2 and IL-1 beta release by ELISA. RESULTS: In co-culture PG
      synthesis by chondrocytes was significantly reduced in the presence of IL-1 beta
      (1 ng/ml) compared to controls. PG content of chondrocyte cultures was reduced
      for controls and IL-1 beta treated co-cultures. Synovial fibroblasts in co
      culture did not show significant change of PG synthesis or content when compared
      to cells in mono-cell culture. PG release into the medium was relatively high in
      co-cultures. IL-1 beta significantly decreased the proliferation rate of
      chondrocytes in co-cultures and slightly increased prostaglandin-E2 release.
      CONCLUSIONS: Co-culturing of osteoarthritic chondrocytes and synovial fibroblasts
      from a single human joint allows interactions between both entities and may offer
      a useful tool to study the effects of mediators or new drugs under more in vivo
      like conditions compared to mono-cell cultures.

PMID- 11247322
TI  - Prevalence of self-reported peripheral joint pain and swelling in an Italian
      population: the Chiavari study.
AB  - OBJECTIVE: To evaluate the prevalence of self-reported joint pain and swelling in
      the peripheral joints of subjects from an Italian general population. To
      correlate the result with demographic data and physical activity. METHODS: A
      total of 4,456 subjects aged 16 years or more listed in four general practices
      were invited to participate in the study and to fill out the ARC questionnaire.
      The 3,294 responders were asked to report: (a) any past occurrence of joint
      swelling lasting more than 4 weeks and the distribution of the swollen joints on
      a mannequin; (b) any joint pain lasting more than 4 weeks; (c) current joint pain
      or swelling; (d) morning stiffness; (e) whether they had been previously told by
      a doctor they had arthritis; and (f) their physical activity according to a three
      class scale. RESULTS: Joint pain was reported by 889 (27%) subjects and joint
      swelling was reported by 463 (14%) subjects. Women reported joint pain and
      swelling more frequently than men, except for the younger age classes. The
      prevalence of joint pain and swelling increased with age in both sexes until age
      55-64, when a plateau was observed. Age was involved in the determination of
      joint pain and swelling. Physical activity was involved only marginally.
      CONCLUSIONS: We found high levels of prevalence of pain and swelling in the
      peripheral joints in a general Italian population. Prevalence was higher in
      Italian subjects than in subjects from China and Pakistan studied using the same
      questionnaire. These differences may reflect cultural and social diversity in the
      perception of disease, as well as true differences in the prevalence of rheumatic
      symptoms across the world.

PMID- 11247323
TI  - The emerging problem of oxidative stress and the role of antioxidants in systemic
      sclerosis.

PMID- 11247324
TI  - Spanish version of the Northwick Park Neck Pain Questionnaire: reliability and
      validity.
AB  - OBJECTIVE: To validate a Spanish version of the Northwick Park Neck Pain
      Questionnaire (NPQ) and to prove its usefulness in clinical practice. METHODS: We
      studied 58 patients with non-inflammatory neck pain of more than 4 months
      duration. A blind back translation of the NPQ was made, and the resulting back
      translation version was then compared with the original. The NPQ comprises 9
      questions with 5 statements of increasing difficulty. Patients completed the
      questionnaire 3 times: on their initial assessment; 8-10 days later (test
      retest); and after physiotherapy treatment 3 months later. Neck pain was assessed
      by a visual analogue scale (VAS). RESULTS: Fifty-three patients completed the
      questionnaire (90%). There was a good intra-class correlation between the test
      retest NPQ (r = 0.63), indicating good agreement. For each of the 9 sections,
      agreement ranged from r = 0.43 to r = 0.85, p < 0.05 in all cases. Correlation
      with the VAS was also good, between r = 0.51 (test) and r = 0.74 (retest) (p <
      0.05 in all cases). Pain measured by the VAS increased according to the NPQ
      score, grouped by percentages (p = 0.003). The mean scores for each section
      increased with that of the intensity of pain, in most sections showing good
      internal consistency. Pain and the NPQ score improved after treatment (56.1 +/-
      20.2 to 29.9 +/- 20.1, p = 0.0001 and 45.9% +/- 12.7% to 28.9% +/- 15.3%, p =
      0.0001 respectively), as did all the other items except for driving (p < 0.05).
      CONCLUSIONS: The Spanish version of the NPQ is a feasible, reliable and valid
      instrument to measure pain in Spanish-speaking patients with chronic neck pain.

PMID- 11247325
TI  - The modulation of chlamydial replication by HLA-B27 depends on the cytoplasmic
      domain of HLA-B27.
AB  - OBJECTIVE: The intracellular persistence of viable Chlamydia trachomatis (CT)
      within the joint is thought to initiate and maintain the inflammatory process in
      CT-induced arthritis. CT-induced arthritis is associated with HLA-B27. Recently
      it was shown that HLA-B27, besides being a T-cell restriction element, can
      directly influence the invasion and/or replication of enterobacteriae and alters
      salmonella-induced signal transduction. It was the aim of this study to analyze
      the effect of HLA-B27 on CT-invasion and replication in human host cells.
      METHODS: Human Hela cells and Hela cells transfected with either HLA-B27 cDNA or
      controls (HLA-A1 cDNA; HLA-B27 mutant = HLA-B27 without cytoplasmic tail; B27Q10
      = HLA-B27 Exon 1-4 linked to Exon 5 of murine Q10) were infected with CT. By
      direct immunofluorescence chlamydial invasion was determined 4 hours post
      infection (p.i.), chlamydial replication 2 days and 4 days p.i. The number of
      infective CT in the different cell lines was determined by titration of the cell
      lysates on Hep-2 cells with subsequent immunoperoxidase staining. RESULTS:
      Invasion was not affected by HLA-B27. However, formation of chlamydial inclusion
      bodies and replication was suppressed by HLA-B27. Genetically engineered mutants
      of HLA-B27 (HLA-B27 mutant, B27Q10) lacking the cytoplasmic tail of HLA-B27 did
      not affect replication. CONCLUSION: The reduction of chlamydial replication by
      HLA-B27 depends on the cytoplasmic domain of HLA-B27, thus providing a new
      hypothesis for chlamydial persistence in HLA-B27 positive reactive arthritis.

PMID- 11247326
TI  - Immunohistologic markers of immune activation and changes of glycosylation of
      serum proteins in primary Sjogren's syndrome.
AB  - OBJECTIVE: [corrected] To assess the possible correlations between the immune
      activation of certain surface antigens at the lip salivary gland (LSG) level, and
      changes in glycosylation of serum proteins in primary Sjogren's syndrome (SS).
      METHODS: LSG biopsy samples were obtained from 22 SS patients (mean age 56.3
      years; mean disease duration 70.8 months) and prepared for immunohistochemical
      analysis using murine monoclonal antibodies for interleukin-2 receptor (IL-2R)
      (CD25) and for the class II major histocompatibility antigen HLA-DR. The
      glycosylation of serum proteins was evaluated in all patients by an enzyme-linked
      lectin assay (ELLA) using concanavalin A (Con A). RESULTS: In LSG specimens the
      presence of IL-2R was observed at the infiltrating level, mainly periductally, in
      13 (59%) cases and on the epithelial cells of 14 (64%) patients. In 13 out of 22
      SS patients (59%) a marked positivity both of the infiltrates and of the
      epithelium was found for anti-HLA-DR monoclonal antibody. The degree of
      expression of different antigens on LSG samples was correlated with their
      histologic class according to Tarpley evaluation. The positivity for IL-2R and
      HLA-DR molecules on glandular tissues was correlated. A significant increase in
      the total Con A reactivity of serum proteins was found in those patients
      expressing IL-2R and HLA-DR antigens on LSG specimens. CONCLUSIONS: The co
      expression of IL-2R and HLA-DR antigens on both the epithelium and infiltrates of
      LSG is consistent with a participation of these cells in the immune process of
      SS. Moreover, changes in the glycosylation of serum proteins seem to be related
      to the presence of these immunoactivation markers of the disease at the LSG
      level, suggesting that the control of protein glycosylation could be mediated by
      the same mechanisms involved in the tissue damage of SS.

PMID- 11247327
TI  - Effect of immune complexes in serum from patients with rheumatoid vasculitis on
      the expression of cell adhesion molecules on polymorphonuclear cells.
AB  - OBJECTIVE: Immune complexes (IC) are frequently detected in patients with
      rheumatoid vasculitis (RV). To explore the pathogenic role of IC in the
      development of vasculitis among patients with rheumatoid arthritis (RA), we
      examined the effect of IC on the expression of cell adhesion molecules (CAM) on
      polymorphonuclear cells (PMN). METHODS: PMN from healthy volunteers were
      incubated with the sera from 26 patients with RA including 9 patients with RV,
      and the expression of CAM on the PMN was assessed by flow cytometry. RESULTS: We
      found that 67% (6/9) of the serum samples from RV patients and 18% (3/17) of the
      samples from RA patients without RV revealed up-regulated CD11b expression. On
      the other hand, 89% (8/9) of the samples from RV patients and 12% (2/17) of the
      samples from RA patients without RV revealed up-regulated CD18 expression.
      However, the expression of CD11a was not affected. Up-regulation of CD11b and
      CD18 on PMN was also induced by the immunoglobulin G (IgG) fraction of the sera
      of RV patients. Moreover, L-selectin expression on PMN was down-regulated by the
      sera or IgG of some patients with RV. These changes in CAM expression on PMN
      induced by IgG of RV patients were not observed when PMN were incubated with the
      IgG of RV patients from which the IC formed by IgG had been removed. CONCLUSION:
      These results suggest that IC formed by IgG in patients with RA are involved in
      the development of vasculitis by affecting the expression of CAM on PMN.

PMID- 11247329
TI  - Lack of association between antiphospholipid antibody and WHO classification in
      lupus nephritis.
AB  - OBJECTIVE: To study the prevalence of antiphospholipid antibody (aPL) in patients
      with biopsy proven lupus nephritis (LN) and to investigate if there is any
      association between the presence of serum aPL and WHO classes. METHODS: Seventy
      one patients (68 female and 3 male, mean age 31 years, range 10-67) meeting ACR
      criteria for the classification of SLE and with biopsy proven LN were included.
      For every patient, we evaluated anticardiolipin antibodies, lupus anticoagulant
      and renal biopsy classified according to the WHO classification criteria
      (activity and chronicity scores were included). Twenty-four hour urinary protein
      at the time of biopsy was considered. RESULTS: Twenty-nine patients had class V
      LN, 27 had class IV, 11 had class III, 3 had class II and 1 had class I. Twenty
      seven (40.2%) patients were aPL positive. The prevalence of aPL positive patients
      was 45% in class V, 33.3% in class IV and 45.6% in class III. We did not find any
      significant association between the presence of aPL and the WHO class (p = 0.61
      with class V, p = 0.31 with class IV and p = 0.73 with class III). There was no
      association between the presence of aPL and activity (p = 0.52) or chronicity
      scores (p = 0.42). We also did not find any association between proteinuria and
      the presence of aPL (p = 0.3). CONCLUSIONS: Our results suggest that there is no
      association between the presence of aPL and the different WHO classes. The
      presence of these antibodies does not seem to be related to histological activity
      or the chronicity of lupus nephritis nor proteinuria.

PMID- 11247328
TI  - Type III procollagen N-terminal propeptide, soluble interleukin-2 receptor, and
      von Willebrand factor in systemic sclerosis.
AB  - OBJECTIVE: To evaluate the blood concentration of type III procollagen N-terminal
      propeptide (PIIINP), soluble interleukin-2 receptor (sIL-2R), and von Willebrand
      factor (vWF) in systemic sclerosis (SSc) patients. METHODS: PIIINP, sIL-2R, and
      vWF were measured in the sera and plasma of 29 SSc patients and 29 sex- and age
      matched healthy controls. Serum PIIINP was determined by radioimmunoassay. Both
      serum sIL-2R and plasma vWF were measured by enzyme-linked immunosorbent assay
      (ELISA). Associations between concentrations and clinical and laboratory features
      were evaluated. RESULTS: Serum levels of PIIINP and sIL-2R were significantly
      higher in the SSc group than in the control group (p < 0.01 for both). No
      differences in serum PIIINP and sIL-2R levels were found between the limited and
      diffuse cutaneous subsets. However, PIIINP concentrations were significantly
      higher in anti-Scl-70 positive SSc patients compared with those of anti-Scl-70
      negative patients (p = 0.01). Serum PIIINP levels were significantly higher in
      SSc patients with restrictive pulmonary function (FVC < 80%) than in patients
      with normal pulmonary function (p < 0.05). The correlation between PIIINP levels
      and FVC (p < 0.05) was negative, but the correlation between PIIINP levels and
      modified Rodnan skin scores (p < 0.05) was positive. sIL-2R levels were not
      correlated with skin and pulmonary involvement of SSc. There was no difference in
      vWF levels between those of the SSc patients and those of the control groups.
      CONCLUSION: These results suggest that serum PIIINP serves as a biologic marker
      for the extent of skin and pulmonary involvement in systemic sclerosis. Increased
      serum levels of sIL-2R in SSc patients support a role for T lymphocyte activation
      in the pathogenesis of systemic sclerosis.

PMID- 11247330
TI  - Reliability of spot samples for assessment of urinary excretion of pyridinoline
      in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To determine how well a spot urine sample of patients with active
      rheumatoid arthritis (RA) can predict 24-hour urinary pyridinoline and
      deoxypyridinoline excretion. METHODS: Urine samples of 11 hospitalized RA
      patients taken on 2 consecutive days at 8 a.m. and 4 p.m. were compared with
      samples from 24-hour collections (gold standard). High-performance liquid
      chromatography was used to measure the collagen crosslink concentrations.
      RESULTS: Sampling time was the only significant factor (repeated measurement
      ANOVA). Significant differences were found between morning and 24-hour samples
      and between morning and afternoon samples, but not between afternoon and 24-hour
      samples. CONCLUSIONS: Samples collected in the afternoon (4 p.m.) give the best
      approximation of 24-hour urinary pyridinoline excretion in patients with active
      rheumatoid arthritis. In longitudinal studies the sampling time should be fixed.

PMID- 11247331
TI  - Changes in systemic levels of insulin-like growth factors and their binding
      proteins in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To determine whether circulating levels of insulin-like growth factors
      and their binding proteins are altered in patients with adult onset rheumatoid
      arthritis. METHODS: Plasma-levels of insulin-like growth factor-I (IGF-I), IGF
      II, IGF-binding-protein 2 (IGFBP-2), and IGFBP-3 were measured by
      radioimmunoassay in 53 patients with clinically active rheumatoid arthritis (RA)
      and in 51 control subjects. RESULTS: In RA patients plasma levels of IGF-II were
      lower (601 +/- 34 vs. 731 +/- 32 micrograms/L (mean +/- SEM); p = 0.005; Mann
      Whitney rank sum test) than in age- and sex-matched controls (n = 30 per group).
      In contrast, plasma levels of IGFBP-2 (412 +/- 40 vs. 254 +/- 20 micrograms/L; p
      = 0.003) and IGFBP-3 were elevated in RA patients (3.34 +/- 0.19 vs. 2.87 +/-
      0.21 mg/L; p = 0.019) as compared with the matched controls. The molar ratio of
      IGF-I to IGFBP-3 was significantly reduced in subjects with RA (0.18 +/- 0.01 vs.
      0.24 +/- 0.02; p = 0.008). Furthermore, in RA patients plasma levels of IGFBP-2
      were positively (r = 0.45), and levels of IGF-2 negatively (r = -0.45) correlated
      with circulating levels of C-reactive protein (p < 0.01 in both cases; Spearman
      rank correlation). CONCLUSION: Increased levels of IGFBPs in RA may result in the
      reduced availability of free IGFs that can bind to IGF receptors. The observed
      changes in the IGF system may thus participate in the catabolic processes in
      rheumatoid arthritis.

PMID- 11247332
TI  - Hypersensitivity vasculitis in adults: a benign disease usually limited to skin.
AB  - OBJECTIVES: To examine the clinical spectrum of hypersensitivity vasculitis (HV)
      in an unselected population of adults and establish differences between patients
      with HV limited to the skin and those with systemic involvement. METHODS:
      Retrospective study of adult patients (> 20 years) with biopsy-proven cutaneous
      leukocytoclastic vasculitis diagnosed as having HV, who were seen at the single
      hospital serving a well defined population between 1984 and 1998. Patients were
      classified as having HV according to the criteria of Michel et al. (9). To
      examine outcome and relapses of the disease only those patients with a follow-up
      of at least 1 year were included in this study. RESULTS: 64 patients with a mean
      follow-up of 4.9 +/- 3.5 (range: 1.1-13.6) years were studied. Ten (15.6%) had
      visceral involvement (3 gastrointestinal and 7 renal manifestations) during the
      course of the disease. The remaining patients had a leukocytoclastic vasculitis
      limited to the skin. When the study was concluded persistent hematuria and
      proteinuria was only observed in 1 patient and none developed renal
      insufficiency. Patients with a history of drug treatment and elevated ESR had
      more systemic complications but the difference was not statistically significant.
      The outcome was excellent in both patients with HV limited to the skin and in
      those with systemic complications during the course of the disease. CONCLUSIONS:
      In unselected adults HV is generally a benign disease confined exclusively to the
      skin. In those patients with systemic manifestations, visceral involvement is
      generally mild and transient.

PMID- 11247334
TI  - Intra-articular sodium hyaluronate reduces pain and improves function in
      osteoarthritis of knee.

PMID- 11247333
TI  - Intraobserver repeatability and interobserver reproducibility in musculoskeletal
      ultrasound imaging measurements.
AB  - OBJECTIVE: To assess the repeatability and reproducibility of ultrasonographic
      measurements at the anterior surface of the femoral neck and iliofemoral ligament
      and on a human tissue-mimicking phantom. METHODS: Two independent investigators
      studied 22 consecutive hips. One investigator had previous experience in
      musculoskeletal ultrasonography (US). The other investigator had undergone a
      short course in hip sonography (only 3 hours). Both investigators were blinded to
      their own and each other's results. On the phantom both observers had taken 10
      vertical measurements at 6 cm deep where two objects were placed at 2 cm from
      each other. Calculation of measurement errors, percent errors and the Bland
      Altman graphic technique were used for analysis of data. RESULTS: After 132
      examinations the first investigator's within-subject standard deviation was 0.4
      mm. The intraobserver error was 4.75%. The second investigator's within-subject
      standard deviation was 0.6 mm and his intraobserver error was 7.00%. The
      interobserver error was 10.91%. After 20 phantom examinations the first
      investigators's intraobserver error was 1.11% and the second investigator's
      intraobserver error was 1.47%. CONCLUSION: An inexperienced musculoskeletal
      sonographer can achieve an acceptable performance if given appropriate training.

PMID- 11247335
TI  - Vesical telangiectasias as a cause of macroscopic hematuria in systemic
      sclerosis.
AB  - A 36-year-old female with diffuse cutaneous systemic sclerosis (dcSSc) developed
      macrohematuria due to vesical telangiectasias that was responsive to
      diathermocoagulation of the vasal lesions. This is the first report of a patient
      with dcSSc and vesical telangiectasias leading to severe macrohematuria that was
      successfully treated with diathermocoagulation.

PMID- 11247336
TI  - Reactivation of primary hypertrophic osteoarthropathy by bronchogenic carcinoma.
AB  - This paper reports 2 cases of primary hypertrophic osteoarthopathy (PHO) which
      evolved into secondary hypertrophic osteoarthopathy (SHO) under the influence of
      bronchogenic carcinoma. The patients had a clinical picture of primary
      hypertrophic osteoarthropathy but without any signs of disease activity until in
      the last several months when a malignant bronchopulmonary condition developed.
      This activated all the symptoms: joint swelling; enlarged fingers and distal
      forearms and legs; moist palms and soles; unpleasant odour of perspiration; and
      deeper folds of the forehead and nasolabial furrow. A bone scan showed increased
      accumulation of the radioisotope in specific regions of the skeleton. To our
      knowledge, no similar cases have been described in the literature.

PMID- 11247337
TI  - Arthropathy of genetic hemochromatosis: a major and distinctive manifestation of
      the disease.
AB  - Genetic hemochromatosis is not a rare disease and represents a frequently
      underestimated cause of arthropathy. Joint involvement is one of the most
      frequent manifestations of the disease and presents typical clinical and
      radiological features that strongly suggest the diagnosis. Joint complaints are
      often the first clinical manifestation of GH. Their identification may be crucial
      to establish the diagnosis in the pre-cirrhotic phase and to institute
      appropriate therapy to prevent organ damage and associated mortality. Recent
      identification of the genetic defect responsible for the disease is leading to
      new insights into the pathogenesis of GH and the associated arthropathy.

PMID- 11247338
TI  - [Restriction analysis of plasmid of the strain Streptomyces sp.27].
AB  - Plasmid pSS27 was found in streptomycete strain isolated from the soil sample in
      the Kyiv region. The paper deals with the data of restriction analysis of
      streptomycete plasmid pSS27 and its molecular weight. Plasmid pSS27 has unique
      restriction sites for endonucleases BglII and EcoRI, there are also the
      restriction sites for SalGI (3 sites), PstI (4 sites), BglI (5 sites), Bsp120I (7
      sites) and SacII (11 sites). The molecular weight of plasmid DNA pSS27, being
      equal to 13.7 +/- 0.2 kb has been determined as a result of its restriction
      analysis.

PMID- 11247339
TI  - [Properties of bacteria of pathovars of Pseudomonas syringae affecting cereals].
AB  - Antigenic properties of Pseudomonas syringae pv. coronafaciens isolated from the
      oats have been studied for the first time, and serologic grouping of the strains
      of P. syringae pv. coronafaciens and P. syringae pv. atrofaciens has been carried
      out. It has been determined that the strains of P. syringae pv. coronafaciens, as
      to availability of specific antigenic complexes belong to two serological groups
      I and V, and thus they are differed from the strains of the pathovar atrofaciens
      which includes four serological groups of the strain isolated from wheat (II, IV,
      V, VI) and five serological groups of the strains, isolated from rye (I, II, IV,
      V, VI). It has been shown that the overwhelming majority of strains of P.
      syringae pv. coronafaciens isolated from the affected plants of the oats belong
      to serogroup V, while P. syringae pv. atrofaciens from the rye--to serogroup I.
      The strains of these bacteria, isolated as epiphytes, dominate in the other
      serological groups.

PMID- 11247340
TI  - [Ecological diagnosis of pyoseptic diseases in newborns using the "Diastaph"
      disc].
AB  - The etiological spectrum of pyoseptic diseases was studied in 113 newborns. It
      was established, that between 187 strains of microorganisms, belonging to 19
      species, 73.3% were staphylococci and streptococci, 25.1%--Enterobacteriaceae,
      1.6%--Candida albicans. Mixed infection, caused by association of 2-5 Gram
      positive and (or) Gram-negative microorganisms, was marked in 51.3% of newborns.
      In cases of mono-infection (42.5%) staphylococci and streptococci were leading
      etiological agents. The possibility of generic identification of staphylococci
      using the diagnostic disks "Diastaph" which contain a new antibiotic batumin has
      been studied. All the isolated staphylococci strains were highly sensitive to
      batumin in contrast to other Gram-positive and Gram-negative microorganisms that
      caused pyodermia in newborns.

PMID- 11247341
TI  - [Use of biological stimulants to decrease negative effect of pesticides on the
      soil microflora].
AB  - Natural and synthetic biostimulants have been studied for their effect on
      resistance of soil microbe associations to pesticides. It has been shown that in
      the presence of growth-stimulating preparations (ivin, emistym, agrostimulin) in
      the microbial groups the number of microorganisms resistant to such fungicides as
      phenpiclonyl, fluodioxonyl, diphenoconasol increases. The activity of redox
      systems which can initiate the oxidative destruction of pesticides increased in
      microbial associations under the simultaneous use of biostimulants and
      fungicides.

PMID- 11247343
TI  - [Formation of erythromycin resistance in Corynebacterium diphtheriae induced by
      long-term effect of the antibiotic].
AB  - Erythromycin resistance induced in Corynebacterium diphtheriae strains by
      subinhibitory concentrations of this antibiotic has been investigated. Six
      strains of C. diphtheriae highly susceptible to erythromycin were grown in the
      broth with 0.5 minimal inhibitory concentration (MIC). After 23-25 cultivations
      the susceptibility to erythromycin in the strains tested began to decrease
      gradually. After 46-52 consequent cultivations the strains became moderately
      resistant, and after 60-72 ones 5 cultures became resistant. The induced
      resistance to erythromycin was associated with that to oleandomycin. The strains
      of C. diphtheriae with induced resistance had no changes in morphology of
      colonies, saccharolytic and adhesive properties and toxigenicity, but their
      growth was slower than that of the original strains.

PMID- 11247342
TI  - [Screening of alpha-N-acetylgalactosaminidase producers among microorganisms of
      different taxonomic groups].
AB  - Screening of producers of alpha-N-acetylgalactosaminidase among 854 strains of
      micromycetes, 171 yeast and 357 bacterial cultures has been carried out. A
      capacity to synthesize the enzyme was revealed in 11% of cultures.
      Representatives of Aspergillus genus (activity--0.11-0.142 un./ml) were most
      active in producing the enzyme. It has been established that glucosidases
      spectrum in the culture liquid of 18 most active strains was characterized by
      complete homogeneity and by the presence of a rather high level (0.5-0.9 un./ml)
      of alpha-galactosidase activity. Complex preparations of alpha-N
      acetylgalactosaminidase and alpha-galactosidase have been obtained from the
      culture liquid of producers by fractionation by ammonium sulphate (30 and 90%
      saturation); their pH- and thermo-optimum, pH- and thermal stability have been
      studied. It was shown possibility to induce alpha-N-acetylgalactosaminidase
      synthesis by a number of carbohydrates (galactose, glucose, galactosamine, and
      glucosamine), complex-forming substances (guanidine HCl), nitroaminoguanidin and
      guanidine carbonate and bovine blood. As a result the strain of Aspergillus niger
      185 III was chosen which activity level could be increased more than 3 times
      (activity--0.6 un./ml as compared to initial one).

PMID- 11247344
TI  - [Current classification and nomenclature of plant viruses (by materials of the
      International Committee on Virus Taxonomy). Part I].
AB  - The rules of classification and nomenclature of plant viruses are reviewed in
      connection with the reports of the International Committee on Viruses Taxonomy.
      The characteristics of the families and genera of plant viruses approved by the
      Committee in 1995 are presented.

PMID- 11247345
TI  - Streptomycete complexes of "Evolution Canyon" soils (Mount Carmel, Natural
      Preserve, Israel).
AB  - It had been studied the quantitative and qualitative structure of the soil
      Streptomyces complexes at three ecotopes of "Evolution Canyon" (Israel) for the
      first time. Numbers of streptomycetes changed from 3'000 to 15'000 CFU per 1 g of
      dry soil depending on edaphic and microclimatic conditions. Eighty-eight species
      and subspecies were found as a whole. Synecological analysis demonstrated the
      high difference between the soil Streptomyces complexes of various Canyon'
      ecotopes, opposite stations and stations across the Canyon.

PMID- 11247347
TI  - [Scientific legacy of K.G. Bel'tiukova--an organizer of studies on
      phytopathogenic bacteria in Ukraine (1900-1971)].

PMID- 11247348
TI  - [Use of the expression coefficient to evaluate the effect of various substances
      on HIV-1 in vitro].
AB  - The effect of some saponins (taurosides) and muramyl peptides (MDP and
      cholesteryl-MDP) on HIV-1 reproduction in Jurkat-tat T cells was studied by the
      coefficient of the virus expression CE. CE was calculated as ratio of
      concentration of HIV p24 to the amount of viable cells. Various substances caused
      diverse effects on HIV-1 propagation (taurosid I and cholesteryl-MDP possessed
      potent antiviral and HIV-stimulating properties respectively). The effectiveness
      of the CE usage for detection of HIV-modulating characteristics of various
      substances was discussed.

PMID- 11247349
TI  - [Use of atomic force microscopy to study the morphology and structure of
      viruses].
AB  - The paper describes AFM methodic approaches in the investigation of viruses (TMV,
      phage T4). A possibility is shown to use this method to obtain high-quality three
      dimensional image of objects without additional treatment with salts of heavy
      metals. The phage T4 was also a model to study the object density, using the
      phase shift of the AFM. Such researches can determine the internal structure of a
      virion and folding of nucleic acid inside a virion.

PMID- 11247350
TI  - [Effect of heavy metals and reclaimers on formation and functioning of legume
      Rhizobium symbiosis].
AB  - The influence of a mixture of salts of heavy metals Cd2+, Cu2+, Pb2+, Zn2+ on the
      efficiency of legume-rhizobial symbiosis and a part of reclaimers in the decrease
      of toxic effect of pollutants have been studied under conditions of the
      vegetative and field experiment on small plots. Concentrations of salts of heavy
      metals were tested in the interval of 1 to 20 MPC (maximum permissible
      concentrations). Negative effect of the tested substances on the growth, photo
      assimilation properties of soybean plants, nodulation intensity, nitrogenase
      activity and yield (correlation coefficients made, respectively, -0.58; -0.86; 
      0.88; -0.84 and -0.86 under reliability 95-99.9%) has been established. The
      increase of concentration of heavy metals was accompanied by the decrease of the
      indices of symbiosis efficiency. The complete suppression of symbiotic system of
      soy-beans was registered under the maximum of test doses which was equal to 20
      MPC. The reclaimer white zeolite has displayed protective properties with respect
      to legume-rhizobial symbiosis against a background of soil contamination with
      high doses of heavy metals. The use of combined reclaimer gypsum-streptomycete
      may be also considered promising for decreasing negative effect of heavy metals
      on legume-rhizobial symbiosis.

PMID- 11247346
TI  - [Action of natural gamma-interferons on functional activity of phagocytes and
      antibody synthesis after vaccination].
AB  - Natural swine and cattle gamma-IFNs were prepared for trials. One dose of gamma
      suiferon contained 1000 IU, that of gamma-boviferon--2000 IU. Three series of
      researches were carried out to estimate the in vitro and in vivo absorbing
      activity of phagocytes (monocytes and neutrophiles), their bactericidal ability
      (on new born pigs and calves, 2 months old animals, sows and cows with calf) and
      antibodygenesis after immunization of animals by colibacteriosis vaccine. It has
      been shown in trials that gamma-IFN increased to significant degree (several
      times, as a rule) the absorbing activity of phagocytes (especially that of
      monocytes in new-born animals). At the same time bactericidal activity of
      phagocytes sharply increased--their functional reserve in experimental animals
      was significantly higher (2-3-times), than in control. Immunization by
      colinebacteriosis vaccine with additional treatment by homologous gamma-IFN 3-4
      times increased antibodygenesis in comparison with control.

PMID- 11247351
TI  - [Accumulation of uranium, plutonium and americium by granulated microbial
      biosorbent].
AB  - A possibility of efficient extraction of 238U, 239Pu and 241Am by microorganisms
      from solutions with activity 520-3200 Bq/l has been shown on the example of
      microbial biosorbent (MBS). MBS presents water-resistant granules consisting of
      living microorganisms and nutrient substances. The ratio MBS:solution being equal
      to 1:100 and 1:20, microorganisms extracts 98.9 and 99.8% of 238U; 99.1 and 99.8%
      of 239Pu, 241Am, respectively. The worked out MBC granules may be utilized by
      burning with the 4-8 decrease of the volume. It is foreseen to use MBS in
      industrial processes of treatment of liquid radioactive waste (LRW) for uranium
      and transuranium elements.

PMID- 11247352
TI  - [Modification of the Hungate vessel for cultivation of facultative and obligate
      anaerobic bacteria].
AB  - Modified Hungate vessel made of native penicillinum bottles and chemical vessels
      has been created and experimentally studied. The vessels can be used for
      cultivation of facultative and obligate anaerobe microorganisms on liquid and
      solid nutrient media. Locking devices of the vessel are described.

PMID- 11247353
TI  - [Use of PCR for the identification of representatives of Lactobacillus and
      Streptococcus].
AB  - REP- and ERIC-PCR genome analysis of lactic acid bacteria of genera Lactobacillus
      and Streptococcus have shown the presence of REP- and ERIC-repetitive sequences
      with high degree of homology. Amplification products which separation in agar gel
      results in formation of a specific fingerprint are obtained under REP- and ERIC
      PCR. It is shown that REP- and ERIC-specific primers can be used for PCR
      identification of both enterobacteria and lactic acid bacteria isolated from
      different ecological niches.

PMID- 11247354
TI  - [Many drugs are produced with risk material from cattle. Can drugs transmit BSE?
      (interview byWaldtraud Paukstadt)].

PMID- 11247355
TI  - [Colleague with broken leg, fractures will not heal. More rapid return to
      practice with ultrasound?].

PMID- 11247356
TI  - [Illegal antibiotics and hormones in swine raising. Is the meat a health risk?].

PMID- 11247357
TI  - [Arthritis, headache, facial paralysis. Despite negative laboratory tests
      Borrelia can still be the cause].

PMID- 11247358
TI  - [The physician's bag and emergency case. What should be in it?].
AB  - The contents of the doctor's bag will be determined by the doctor concerned and
      will depend on his medical training and specialization, on local conditions, the
      nature of his field of activity, and on the organization of medical emergency
      services. A selection of commonly employed preparations, classified by indication
      is proposed and discussed. In addition to the "drug collection", the essential
      "hardware" (syringes, stethoscope, etc.) and "software" (prescription forms,
      accounting forms, list of hospital telephone numbers, etc.) are also listed. The
      specific demands to be met by the contents of an emergency kit are discussed
      separately.

PMID- 11247359
TI  - [Emergencies in general practice, 1. Headache as an alarm symptom].
AB  - Primary headache, such as migraine and tension type headache is a common symptom
      in patients presenting in emergency departments. Suspicious of secondary headache
      is a medical history of new onset, changing character of a previously known
      headache, resistancy to medication or symptoms which are not typical of primary
      headache.

PMID- 11247360
TI  - [Allergy to dust mites. During the heating season asthma threatens].

PMID- 11247361
TI  - [Iron deficiency. When parenteral substitution?].

PMID- 11247362
TI  - [When physicians become manic or depressive... Self treatment is malpractice!].

PMID- 11247363
TI  - [Examination techniques in lumbar pain syndrome. 1: Evaluating the function of
      the lumbar vertebrae in discogenic and arthro-ligamentous lumbar pain syndrome].

PMID- 11247364
TI  - [Diagnostic quiz. "Grippe" following visitors from Angola. Tuberculosis (primary
      complex)].

PMID- 11247365
TI  - [Salmeterol plus fluticasone--a powerful team. New combined preparation improves
      compliance].

PMID- 11247366
TI  - [Diskus--an innovative inhalation system. Simple administration, reliable drug
      liberation].

PMID- 11247368
TI  - [Up to 6,000 DM per month profit. Nice subsidy for nutrition counseling].

PMID- 11247367
TI  - [Insurance carriers want to lower fixed rates. Physicians must deal with the
      anger in their practices].

PMID- 11247369
TI  - [Treating not only blood pressure. Advantages for microcirculation].

PMID- 11247370
TI  - [Well tolerated sartans. More normal blood pressure finally?].

PMID- 11247372
TI  - [Modern calcium channel blockade. Lowering blood pressure with added benefits].

PMID- 11247373
TI  - [Acute coronary syndrome. Statins in the early phase save lives].

PMID- 11247371
TI  - [New glucose regulator. More comfort for the type 2 diabetic patient].

PMID- 11247374
TI  - [Broad-spectrum fluoroquinolones. Passed safety tests up to now].

PMID- 11247375
TI  - [Ulcers after use of non-steroidal anti-inflammatory drugs. Can the risk be
      calculated?].

PMID- 11247377
TI  - [Friction electricity to high frequency therapy. With current].

PMID- 11247376
TI  - [Early recognition not hopeless. Alzheimer disease can be delayed].

PMID- 11247378
TI  - Effects of an urban high school-based child care center on self-selected
      adolescent parents and their children.
AB  - This study examined the effects of an urban high school-based child care center
      on parenting teens and their children enrolled during 1995-1998. Retrospective
      record review of 52 low-income, urban adolescent parents enrolled at the Celotto
      Child Care Center (CCCC) during the period of study was conducted from the CCCC
      and the high school records. Mean age of the student parents was 17 years (s.d. =
      1.3) and mean grade level was 11.2 (s.d. = 1). Most parents were female (98%) and
      African American (62%). Children enrolled at CCCC had a mean age of 10 months
      (s.d. = 10.8). Students using the services of CCCC showed improvement in overall
      grade point averages, and 100% were educationally successful as defined by
      promotion to the next grade or graduating from high school. None of the students
      experienced a repeat childbirth during the period of CCCC enrollment. Ninety
      percent of children were up-to-date with pediatric health visits and
      immunizations. These results lend strong support to the importance of extending
      child care and social support services to teen parents, and for the
      implementation of high school-based child care centers as alternative sites for
      these critically important services.

PMID- 11247379
TI  - A school-community partnership for at-risk students in Pennsylvania.
AB  - This four-year, school-community health improvement project addressed
      fragmentation and under-utilization of services of an at risk population in a
      county in central Pennsylvania. A population profile was developed that included
      demographic, attitudinal, and behavioral information as well as information
      related to liabilities and assets that affect resiliency and decrease or increase
      the likelihood of academic success. The profile was used in the planning and
      implementation of risk-reduction strategies that promote a healthy family and, in
      turn, a healthy community. More than 50 local, state, and national organizations
      as well as individuals volunteered or provided services at each school. The
      project produced a 22% increase in parental involvement in school activities; a
      15% increase in parental involvement in educational sessions; a 22% increase in
      volunteers within the school; and a 75% decrease in truancy.

PMID- 11247380
TI  - What do master teachers consider important in professional preparation for school
      health education.
AB  - The purpose of the two studies presented in this article was for master health
      education teachers at the middle school and high school levels to identify
      content, skills, and experiences that are important for professional preparation
      in school health education. Teachers were identified by health education
      directors in state departments of education. The Delphi technique was used for
      data collection and analysis for both studies. Teachers completed three rounds of
      questionnaires gradually coming to consensus on content, skills, and learning
      experiences in nine areas related to professional preparation. Fifty high school
      teachers representing 29 states and 46 middle school teachers representing 32
      states provided input. Professional preparation priorities were identified for
      both middle school and high school levels. Four responses--awareness/use of a
      variety of instructional techniques; skill in working with parents; knowledge of
      health content; and awareness of, and ability to work with community
      agencies/organizations--were ranked as priorities at both levels. Recommendations
      for future research and practice activities are presented.

PMID- 11247381
TI  - Pilot-testing a cancer education curriculum for grades K-6.
AB  - Risk behaviors established during childhood including tobacco use, sunning, and
      eating habits contribute to most adult cancers. This project pilot-tested a
      developmentally appropriate cancer prevention curriculum for grades K-6, using a
      treatment group only design with pretesting and posttesting using a standardized,
      semistructured interview and involving 67 students (77% of eligible students)
      attending mixed grade classes. A seven-unit curriculum based on cognitive
      development, social cognitive, and social influence theories was taught by
      classroom teachers. Students showed a significant (p < .0001) gain in conceptual
      understanding for causality and prevention of cancer; the gain for causality of
      cancer was comparable to the baseline difference between kindergarten and the
      highest (5-6) grade. Significant gains in factual knowledge and decreases in
      misconceptions about casual contact also were documented. A developmentally based
      elementary school cancer prevention curriculum can enhance young children's
      conceptual understanding and factual knowledge of common contributors to adult
      cancers.

PMID- 11247383
TI  - Incorporating expanded school mental health programs in state children's health
      insurance program plans.

PMID- 11247382
TI  - Support for school-based reproductive health services among South Carolina
      voters.
AB  - In 1997 a statewide random digit-dialed telephone survey of 534 South Carolina
      registered voters was conducted to determine level of support for school-based
      reproductive health services. Results indicated most voters supported services in
      secondary schools that would provide students with information and counseling
      about contraceptive methods and refer students to community-based agencies for
      abstinence education and counseling. Voters were less supportive of reproductive
      health services that would diagnose or treat sexually transmitted diseases, test
      for pregnancy, refer students to community-based agencies for contraceptives, or
      make contraceptives available to students at school. Significant associations in
      support for school-based reproductive health services were reported based on
      income, personal beliefs, intentions, and outcome expectations regarding
      sexuality education and contraceptive availability. These data reinforce the need
      for school-aged youth in South Carolina to have access to reproductive health
      services within their communities, outside of the school setting.

PMID- 11247384
TI  - Synthesizing the relationship between homeostasis and health.

PMID- 11247385
TI  - A Medicaid reimbursement program in Colorado schools.

PMID- 11247386
TI  - Are teachers using computers for instruction?

PMID- 11247387
TI  - 1st Conference on Reward Deficiency Syndrome: Genetic Antecedents and Clinical
      Pathways. San Francisco, California, USA. November 12-13, 2000. Abstracts.

PMID- 11247388
TI  - Morphological changes and morphological-functional correlations in acute
      experimental ischemia/reperfusion pancreatitis in rats.
AB  - The etiology of acute pancreatitis, apart from alcohol abuse and cholelithiasis
      may also include a vascular component responsible for pancreatic ischemia. It is
      now acknowledged that chronic pancreatitis may be a consequence of the acute
      variant, but it remains unclear what factors influence this sequence of
      morphological changes. In order to clarify this issue we proposed a model of
      experimental acute pancreatitis in rats induced by a 30 min reduction of blood
      flow in inferior splenic artery followed by reperfusion. Rats were sacrificed at
      1 h, 12 h, 24 h, and 2, 3, 5, 7, 14, 21, 28 days after cessation of ischemia. We
      performed histopathological examination of pancreatic tissue and measured
      pancreatic blood flow, plasma amylase activity and interleukin-1 beta
      concentration. The present findings indicate that transient pancreatic ischemia
      leads to the development of acute necro-haemorrhagic pancreatitis. The
      morphological features of acute inflammation are correlated positively with
      functional disorders. In some cases the features of chronic pancreatitis may
      appear transiently after the acute phase, whereas the repair of postinflammatory
      injury involves the regeneration of acinar cells.

PMID- 11247389
TI  - Primary splenic B-cell lymphoma (marginal zone lymphoma). Clinicopathological
      evaluation of 10 cases.
AB  - SMZL has been included in the REAL classification of lymphoid neoplasms (1994) as
      an entity. It affects middle aged adults presenting with splenomegaly, mild
      lymphocytosis and in 40% of cases with the presence of monoclonal paraprotein.
      Our material includes 10 patients (6 women + 4 men). In all patients bone marrow
      biopsy was the initial material for histopathological examination. With
      characteristic intertrabecular nodular interstitial infiltrates of CD20+ small
      lymphocytes and corresponding clinical data (splenomegaly, lymphocytosis in
      peripheral blood and sporadic elevation of IgM levels) it was very suggestive of
      SMZL diagnosis. Splenectomy was the treatment of choice. The spleen showed
      micronodular white foci in all cases. Morphologically the pattern of white pulp
      involvement was observed with lymphoma infiltrates as well as small foci in the
      red pulp. The white pulp showed follicles surrounded by a wide marginal zone,
      resembling reactive splenic follicles. A corona-like rim consisted of medium size
      cells with abundant clear cytoplasm, resembling monocytoid B cells, often with
      plasmacytoid differentiation, or centrocyte-like cells. Smaller aggregates of
      these cells were present in the red pulp. Lymphoma cells were CD20+, bcl-2 and
      IgM+. In all cases monoclonal kappa light chains were found. Although SMZL is a
      disseminated lymphoma at diagnosis, its course is indolent and splenectomy is the
      treatment of choice. Clinical and histopathological differential diagnoses
      include hairy cell leukemia and secondary involvement of the spleen by
      infiltrates of nodal B-cell lymphomas.

PMID- 11247390
TI  - ALS-Plus syndrome. A clinical and neuropathological case study.
AB  - ALS-Plus syndrome occurs rarely and usually presents typical ALS phenotype
      associated with dementia, Parkinsonism or both. We reported a case of sporadic,
      definite ALS with pseudobulbar palsy, emotional lability and selective cognitive
      deficit in the presence of frontal lobe dementia. Neuropsychological tests
      predominantly demonstrated perserveration and dynamic apraxia, CT and MRI scans
      showed widened subarachnoideal spaces in the frontal and temporal regions. The
      neuropathological findings confirmed ALS processes i.e. atrophy of motor nuclei
      in brainstem and anterior horns of cervical spinal cord and showed mild atrophy
      and status spongiosus in the frontal lobes. These findings suggest the co
      occurrence of sporadic ALS and frontal lobe dementia: ALS-Plus syndrome.

PMID- 11247391
TI  - Membrane-bound paracrystalloid structures in alveolar rhabdomyosarcoma.
AB  - We report here a case of an alveolar rhabdomyosarcoma in a 25-year-old woman.
      Ultrastructural examination revealed a few periodical membrane-bound
      crystalloids, similar to those regarded as specific for alveolar soft-part
      sarcoma. Our study provides evidence supporting a myogenic origin of those
      periodic structures, and simultaneously a myogenic origin of alveolar soft-part
      sarcoma.

PMID- 11247392
TI  - Syringomatous adenoma of the nipple.
AB  - Syringomatous adenoma of the nipple (SAN) is an extremely rare neoplasm of the
      breast. We present a case of 41-year-old female with a retroareolar mass in her
      left breast. The patient has been operated on twice and remains free of disease
      for 20 months after the second operation. The nosological status of SAN and its
      relationship to the microcystic adnexal carcinoma of the skin is discussed.

PMID- 11247393
TI  - 2000 World Health Organization classification of tumors of the nervous system.
AB  - This is a review of the 2000 World Health Organization (WHO) classification of
      tumors of the nervous system. It contains an overview of the most important
      changes and short descriptions of the new entities or variants of already
      existing entities included in the current classification. These are: chordoid
      glioma of the third ventricle, cerebellar liponeurocytoma, large cell
      medulloblastoma, medulloblastoma with extensive nodularity and advanced neuronal
      differentiation, atypical teratoid/rhabdoid tumor, perineuroma, and rhabdoid
      meningioma. In contrast to the former WHO tumor classification series, the
      present one is based on the complex criteria, which include not only the clinical
      course and histologic appearance of the neoplasm but its immunophenotypic
      features and molecular/cytogenetic profile as well. Thus, it is strongly disease
      oriented and uses extensively the recent advances in the basic sciences.

PMID- 11247394
TI  - Factors associated with progression of primary gastric marginal zone B-cell
      lymphomas of mucosa-associated lymphoid tissue (MALT type).
AB  - Sixty cases of primary MALT type lymphomas were subjected to a retrospective
      analysis, which assessed the proliferative (PI) and apoptotic (AI) indices. The
      MIB-1 antibody was used for the Ki-67 proliferative antigen epitope, as well as
      the Apoptag In Situ Apoptosis Detection Kit (Oncor). The group included 32 low
      grade and 28 high-grade lymphomas. In addition, the high-grade lymphomas group
      was divided into subgroups, depending on the presence or absence of a low-grade
      component. Significant differences were demonstrated in proliferative and
      apoptotic indices for cases differing with respect to their histological grade
      and stage. In low-grade lymphomas, the increase of AI value was associated with
      the increase of blast cells in the neoplastic infiltrate. It was necessary to
      exclude from this group cases of intensified plasmocytic differentiation, as such
      intensified differentiation alone was associated with increased AI values also.
      Considerable variations were noted in AI and PI values, even in groups with the
      same histological grade. The results suggest a potential clinical importance of
      AI and PI evaluations, stressing the necessity of treating each case of primary
      MALT type lymphoma individually. It appears that histological grade and stage
      evaluation alone may be insufficient when planning the management and
      prognosticating the response to therapy.

PMID- 11247395
TI  - Endocrine cells in colorectal carcinomas. Immunohistochemical study.
AB  - Immunostaining for chromogranin A, serotonin, glucagon and somatostatin revealed
      the presence of endocrine cells in 20 (35.1%) out of 57 randomly selected
      colorectal carcinomas. Expression of a general "neuroendocrine" marker,
      chromogranin A was detected in 18 tumours, whereas in the remaining two
      carcinomas positive reactivity with glucagon only was seen. Serotonin was
      expressed in 9 carcinomas, glucagon in 5 and somatostatin in 4 carcinomas. In 3
      tumours coexpression of active products was found: in one--serotonin and
      glucagon, in another--serotonin and somatostatin, and in the last one--serotonin,
      glucagon and somatostatin. In 6 carcinomas expressing chromogranin A there was no
      expression of active products. Twelve carcinomas were assigned to a group with a
      small number of endocrine cells (up to 50/cm2 of tumour cross sectional area), 6
      to a group with an intermediate number of endocrine cells (over 50 to 500/cm2)
      and 2 to a group with a large number of endocrine cells (over 500/cm2). The
      endocrine cells were significantly more frequent in less advanced and better
      differentiated carcinomas and in neoplasms with abundant mucin production. The
      cells were an integral part of glandular structures of the carcinoma, which
      argues in favour of a unitarian theory, i.e. common, endodermal origin of
      endocrine cells and other cellular elements of intestinal epithelium.

PMID- 11247396
TI  - Correlation between type and grade of ductal carcinoma in situ and concomitant
      invasive ductal carcinoma of the breast.
AB  - Morphological analysis was made in a group of 52 breast cancers, in which ductal
      carcinoma in situ (DCIS) was coexisted with invasive ductal carcinoma. DCIS was
      graded according to the cytological, Van Nuys and Holland classifications sharing
      a criterion of evaluating the degree of cancer cell nuclear atypia, and the
      histological classification. Histological grading of invasive breast carcinoma
      was based upon the modified Bloom and Richardson classification. Statistical
      analysis revealed a significant correlation between grades of invasive carcinoma
      and concomitant DCIS. This indicates a high prognostic value of above-mentioned
      DCIS classifications, proving their clinical usefulness. The Van Nuys
      classification should be recommended as its criteria are precise and there is no
      need to isolate DCIS with intermediate nuclear atypia, which improves assessment
      of the lesion.

PMID- 11247397
TI  - Correlative ultrastructural and immunohistochemical study of developing vascular
      basement membrane in postnatal rat spinal cord.
AB  - We investigated the development of vascular basement membrane in immature spinal
      cord vessels during rat spinal cord myelination. Correlative ultrastructural and
      immunohistochemical study indicated that fibronectin was the first component of
      extracellular matrix. Then, on the 9th postnatal day, laminin appeared. At that
      time, lamina lucida of vascular basement membrane was not detectable. On the 15th
      day, when collagen IV was visible, lamina densa and lamina lucida were
      occasionally observed. All components of basement membrane--fibronectin, laminin,
      collagen IV, alpha-2 laminin (merosin)--and ultrastructural division into two
      layers were detected on the 25th postnatal day. The results of this study
      indicates that a gradual development of endothelium in immature rat spinal cord
      blood vessels leads to a gradual increase of synthesis of extracellular matrix
      components.

PMID- 11247398
TI  - Epithelial-myoepithelial carcinoma of the bronchus.
AB  - The authors describe an extremely rare case of epithelial-myoepithelial carcinoma
      of bronchial mucous glands involving lower lobe of the right lung, which was
      detected on a routine radiological examination in a 34-year-old woman, and then
      surgically resected.

PMID- 11247399
TI  - Neoplasms of the central nervous system of lipoid origin.
AB  - In general tumours of lipoid origin are benign. A high proportion of cases are
      mesenchymal neoplasms localised in subcutaneous tissue. Neurological signs
      related to compression of neural structures by fat within the vertebral canal
      were first presented in 1975. The lipogenic neoplasms represent 1-4% of spinal
      tumours, and generally are associated with congenital disorders of the spine.
      These fatty swellings are usually benign, but penetrating deeply into the spine,
      and connecting with spinal cord, cauda equina or filium terminale, they produce
      deficits. The deficits may be present at birth but they may also occur in the
      middle age. These events are classified as epidural lipomatosis (mostly observed
      in patients on chronic steroid treatment) or as lipoma, common in spinal
      disraphism. Intracranial tumours of lipoid origin are very rare (0.06-0.5% of
      brain tumours), and are probably congenital. They occur anywhere within the
      cranium, however a high proportion of cases tend to be located around the
      midline, and approximately 50% of tumours are found in the corpus callosum.
      Usually they are asymptomatic, and when the symptoms occur, they are frequently a
      result of general clinical condition. The authors present three cases of
      lipomatous tumours; one intracranial and two of spinal location.

PMID- 11247400
TI  - [Factors influencing the length of hospital stay of patients qualified for
      elective carotid endarterectomy].
AB  - The aim of this retrospective study was to identify the factors affecting long
      hospital stay of patients who underwent carotid endarterectomy. The analysis was
      based on 233 records of all patients operated on between 1995 and 1998. We have
      found that the main reasons of lengthened preoperative hospitalization were:
      insulin dependent diabetes and admission on the day excluding the chance of
      operation in a short time. Postoperatively, monitoring in intensive care unit and
      unfounded delay of discharge were the leading reasons of prolonged hospital stay.

PMID- 11247401
TI  - [Effect of asymmetric respiratory exercise therapy on respiratory system
      function; evaluation using spirometric examination in children with idiopathic
      scoliosis].
AB  - Current work presents the results of spirometric examinations in 124 children
      aged 5 to 16 years (mean age 12.1 years) suffering from idiopathic scoliosis.
      Children were treated according to asymmetric respiratory exercises method
      applied in period of 24 days. Healthy children living in Upper Silesia industrial
      region were the control group. Examined scoliotic group was characterized by
      generally mild lung function impairment, although the values of spirometric
      indexes tended to deplete with time of duration and severity of the scoliosis.
      Especially the tendency of the forced expiratory volume in first second (FEV1)
      decrease was apparent, as well as maximal expiratory flows MEF50 and MEF25, in
      conjunction with Cobb angle increase. Slight but evident increase of forced vital
      capacity (FVC) and FEV1 was observed as a result of rehabilitation utilizing
      asymmetric respiratory exercises method.

PMID- 11247402
TI  - [Detection of silent ischemia symptoms in patients with carbohydrate metabolism
      disorders].
AB  - Early detection of silent ischaemia plays an important role in prevention of
      sudden cardiac death. Glucose metabolism disturbances are important risk factor
      of ischaemic heart disease. More frequent occurrence of silent ischaemia in
      patients with diabetes mellitus has been reported in several studies. We studied
      24-hour Holter ECG monitoring of 335 patients with stable angina pectoris.
      Patients were divided in two groups. The first group consisted of 158 patients
      with glucose metabolism disturbances, the second-controlled group consisted of
      177 patients without these disturbances. The aim of this study was to analyse the
      frequency of occurrence of silent ischaemia according to the grade of glucose
      metabolism disturbances. We only found that silent ischaemia is more frequent in
      patients with higher grade glucose metabolism disturbances. Additionally, we
      found that more frequent occurrence of silent ischaemia may depend on coexisting
      hypertension and hypertriglyceridemia. The comparison of Holter ECG monitoring
      and exercise test in detection of silent ischaemia has shown that both methods
      are useful in the detection of silent ischaemia.

PMID- 11247404
TI  - [Selection of bronchoscope type for removal of foreign bodies from the lower
      respiratory tract based on personal experience].
AB  - 32 patients, in whom bronchoscopy was performed due to the removal of foreign
      body from the lower respiratory tract were described. Age of the patients
      clinical symptoms and a time lapse between aspiration and removal of foreign body
      from the lover respiratory tract and localization of foreign body in the
      particular bronchus were analysed. We conclude, that rigid bronchoscopy is still
      more useful and safe method of foreign body removing from the lower respiratory
      tract.

PMID- 11247403
TI  - [Levels of cystatin C, activity of antipapain and antitrypsin in plasma of
      patients with diabetes mellitus type 2].
AB  - In plasma of 72 patients with diabetes mellitus type 2, cystatin C concentration,
      the antipapain as well as antitrypsin activities were determined. Statistically
      significant increase of levels of all the examined parameters (higher for
      inhibitors of cysteine proteases) was found in comparison to healthy persons.
      When considering types of vascular complications, the highest concentration of
      cystatin C and the strongest positive correlation with antipapain activity was
      found in the group of patients with microangiopathy. It might be connected with
      glomerular damages. Only antipapain as well as antitrypsin activities showed
      significant correlation with glycaemic control as measurement by glycated
      haemoglobin concentration.

PMID- 11247405
TI  - [Knowledge and competence of primary care physicians in diagnosis and treatment
      of nervous system diseases].
AB  - The diagnosis and treatment of neurological diseases in primary health care
      requires not only the specialistic knowledge but also easy access to the
      diagnostic and rehabilitation procedures and co-operation with neurologist. The
      aim of this study was to specify the quality of diagnosis and treatment of the
      neurological diseases in primary health care. The knowledge and practical skills
      of physicians working in the primary health care were analysed paralell to their
      possibilities of the diagnostics and rehabilitation of the patients suffering
      from neurological disturbances. Furthermore the quality of the co-operation with
      specialised neurologist was assessed. The research was carried on in 1999 using
      anonymous inquiry in the group of 151 primary health care (p.h.c.) physicians
      participating in the teaching courses in the Institute of Agricultural Medicine
      in Lublin. The research proved that patients with disturbances of the nervous
      system were frequently admitted to the primary health care outpatient
      departments. Among the diseases the low back pain, headaches and dizziness
      dominated. Most of the p.h.c. physicians used to examine patients by themselves
      but were sceptical about their skills. They tried to diagnose the neurological
      problems according to their abilities. The final effect was satisfactory, however
      neurological diseases treated by p.h.c. physicians were limited to the low back
      pain, headache, zoster and the febrile seizures. Only small percentage of
      patients was treated properly and in accordance with new trends in neurological
      art. Also the co-operation between primary health care physician and neurologist
      was not satisfactory.

PMID- 11247406
TI  - [Pulmonary function in patients treated for esophageal cancer].
AB  - The data concerning lung function and smoking history were evaluated before
      oesophagus cancer surgery in 54 patients. The parameters of forced expiration and
      inspiration (FVC, FEV1, PEF, FEF and VCin) were measured and as well as the
      bodyplethysmography was performed. More than 90% of patients smoked cigarettes.
      Mean values of FVC and FEV1 were within normal range in the whole group but
      FEV1/FVC (%) was decreased. Current smokers had the highest airways resistance.
      In the group of former smokers RV and ITGV were elevated. All mean values of
      forced expiratory flow parameters were below normal range. In the whole examined
      group spirometry revealed 28.9% of patients with FEV1 lower than 80% of predicted
      value and 83.7% of patients with small airways obstruction (FEF25 < 80% of
      predicted value. There were 74% of patients with Raw > 0.3 kPa/l/s. The high
      frequency of airways obstruction in the evaluated group of patients enhanced the
      risk of bronchopulmonary complications during surgery as well in postoperative
      period.

PMID- 11247407
TI  - [Identification of mutation and polymorphic changes in the CFTR gene of patients
      with obstructive azoospermia].
AB  - Obstructive azoospermia is one of the symptoms of congenital bilateral absence of
      the vas deferens (CBAVD)--disease which is suggested as primarily genital form of
      cystic fibrosis. CBAVD is a result of mutations and polymorphisms in CFTR gene.
      We studied 9 the most common mutations and identified 3 mutations (delta F508,
      R117H, G542X). The study showed that: 37.1% of CBAVD patients (13 out of 35
      examined patients) carried mutations in a single or both copies of the gene. We
      also found the increased frequency of IVS8-5T allele in this group. No increased
      frequency of mutations in CFTR gene was found in group of men with incorrect
      spermatogenesis.

PMID- 11247408
TI  - [The value of lipofuscin determination in blood at the pathophysiologic clinic-
      literature review].
AB  - Lipofuscin is a conjugated Schiff base delivered from reaction of
      malonylodialdehyde with proteins, amino acids and phosphatidylethanolamines. It
      emits yellow-green autofluorescence in ultraviolet light. It is believed to be
      one of the parameters of oxidation stress in vivo. Increased amount of lipofuscin
      in the blood has been found in uremia, diabetes, aging process, adult respiratory
      distress syndrome and multiple organ failure.

PMID- 11247410
TI  - [How nitrate tolerance be prevented in the treatment of ischemic heart disease?].
AB  - Organic nitrates are widely used for chronic treatment of ischaemic heart
      disease. However, the clinical value of long-term nitrate therapy is limited by
      the development of tolerance to their anti-anginal effects. This paper examines
      the different effects of nitrates, especially cellular effects. The theories put
      forward to explain nitrate tolerance are examined, including recent work on
      vascular superoxide and endothelin-1 regulation. Clinically, tolerance can be
      prevented by intermitted dosing of nitrates. This topic, and the practical
      results of work using other pharmacologic interventions in a clinical setting are
      discussed in the final section of this article.

PMID- 11247409
TI  - [Mechanisms regulating appetite and energy expenditure].
AB  - The nutrition instinct is regulated by central nervous system, hypothalamus,
      rhinencephalon, lobus limbicus, corpus amygdaloideum and cortex cerebri. These
      centers constantly get impulses informing about nutrition situation of tissues.
      There are: psychical, nervous, humoral and metabolic impulses, which are
      organized in central nervous system. Central nervous system sends the centrifugal
      impulses to regulate the mechanisms. There is dependence present between
      neurogenic, momentary and longwave regulation and thermogenesis.

PMID- 11247412
TI  - [Laboratory diagnosis and some remarks concerning mortality and treatment of
      children with myocardial infarction].
AB  - There are presented in the paper laboratory findings, echocardiographic and
      radioisotope studies results, as well as heart catheterization including
      coronarography in the pediatric patients suffering from heart infarction.
      Mortality and malignant arrhythmias due to heart infarct in pediatric age are
      shortly discussed, too. At last there are some remarks concerning myocardial
      infarction treatment in children.

PMID- 11247411
TI  - [Long-term controlled release of drugs].
AB  - The surveys of long-term controlled drugs supply systems have become recently one
      of more important branches of pharmacy. Many systems were elaborated. The systems
      differ from each other by the mechanism and time of drug release and the way of
      administering it. A large number of polymers have been developed with the
      capability of controlling the release rate over a long period of time (from 12 hr
      to 5 years). The programmed delivery of drugs offers advantages over conventional
      methods of administration. Controlled release drug delivery systems include oral,
      transdermal, injectable, implanted, intrauterine and intravaginal systems. In
      this paper different sustained-release systems in current use are reviewed.

PMID- 11247413
TI  - [Contemporary views on the subject of male hormonal contraception].
AB  - Contemporary studies of male hormonal contraception are presented. The authors
      used many forms of testosterone (testosterone enanthate, testosterone buciclate),
      in their works and they estimated its activity in mono- and politherapy.
      Parallely the effect of this hormone was tested on some parameters of endocrine
      system, blood cell count, mood and sexuality of normal men. The alternative forms
      for intramuscular injections can be oral administrations, implants or vaccines.

PMID- 11247414
TI  - [Simultaneous coronary artery bypass grafting on the beating heart without
      assisted circulation and radical modified Patey mastectomy--case report].
AB  - A case of 53-year-old female with unstable angina pectoris and primary right
      breast cancer is presented. Simultaneous operation including coronary artery
      bypass grafting and modified radical mastectomy was performed. On the beating
      heart coronary anastomoses were done without cardiopulmonary bypass (CPB) through
      median sternotomy (OPCABG). Immediately after OPCABG cancer operation was
      performed under stable hemodynamics without any bleeding tendency. There were
      neither perioperative nor postoperative complications noticed. Three months after
      operation adjuvant local radiotherapy was started. Concomitant surgical treatment
      seems to be safe and beneficial in carefully selected patients who have
      surgically correctable coronary artery disease and potentially curable breast
      cancer.

PMID- 11247415
TI  - [Epileptic seizure as the first neurologic symptom of Recklinghausen disease in a
      10-year old boy with a brain tumor].
AB  - Epileptic seizure as the first neurological symptom in von Recklinghausen disease
      (Neurofibromatosis type 1, NF 1) in 10 year old boy with cerebral tumour was
      described. Non-typical location of von Recklinghausen disease in central nervous
      system, characteristic for neurofibromatosis type II (NF2), besides rare
      manifestation of cerebral tumour in the form of generalized convulsions, without
      neurological focal and brain oedema symptoms induced us to describe this case.

PMID- 11247416
TI  - [Repeated excision of abdominal aortic aneurysm--case report].
AB  - A case of 69-year-old male patient with recurrent abdominal aortic aneurysm is
      described. The patient had been successfully operated on for infrarenal abdominal
      aortic aneurysm 4 years before, and 2 months postoperatively dilatation of
      juxtarenal part of abdominal aorta was diagnosed in ultrasonic examination. Due
      to progressive enlargement of juxtarenal aneurysm the patient was admitted to
      hospital again and operated on. Excision of aneurysm with implantation of both
      renal arteries to the prosthesis was done. The perioperative course was
      uneventful. Authors emphasize the importance of evaluation of abdominal aorta
      after operative treatment of aneurysm (ultrasonic, CT, MRI) to diagnose recurrent
      aneurysms.

PMID- 11247417
TI  - [Teaching medicine of disasters in the Military Academy of Medicine].
AB  - In the article the author's teaching programme of The Medical Military Academy of
      Lodz was presented. The programme is executed in an interdisciplinary way on each
      year of the studies, in full time of 80 hours of lectures: 30 hours of theory and
      50 hours of practice. The programme takes into consideration the gradation of
      difficulty. In the teaching process particular emphasis is placed on the
      standards of proceedings in cases of life threat.

PMID- 11247418
TI  - [Blood circulation disorder in thoracic outlet compression syndrome].
AB  - In 123 patients the peculiarities of the blood circulation disorder of upper
      extremities in presence of the compression thoracic outlet syndrome were studied.
      The m. scaleni syndrome was noted in 61 (49.5%) patients, cervical rib syndrome-
      in 9 (7.3%), costoclavicular syndrome--in 22 (18%), hyperabduction syndrome--in
      31 (25.2%). The dependence of the blood circulation disorder from the kind of
      compression was established, permitting to choose the method of treatment
      differentially and to improve its results.

PMID- 11247420
TI  - [Applications of immunomodulators in complex of treatment of the soft tissue
      purulent wounds].
AB  - In 31 patients with purulent wound of soft tissues more rapid cleansing and
      healing of the wound, the immunity indexes normalization were noted while
      application of immunomodulator thymogen in combination with the siliceous sorbent
      sillard application and adaptogenic preparation--tincture of Echinacea Purpurea.

PMID- 11247419
TI  - [The influence of antral on the immunological and hemodynamic indices in the
      treatment of purulent-necrotic complications of diabetes mellitus].
AB  - Efficacy of application of antrahl in 41 patients with purulent-necrotic
      complications of diabetes mellitus was studied. Positive effect of the antrahl on
      the disease course was established, application of preparation had promoted the
      surgical intervention volume reduction and duration of treatment in hospital
      also, as well as positive dynamic of the immune and microhemodynamical indexes.

PMID- 11247421
TI  - [Contemporary aspects of treatment of the gun shot thoracic wounds].
AB  - The traumatic disease occurrence with characteristic periods of course constitute
      the peculiarity of gunshot penetrating thoracic wound (PTW). Tactics of treatment
      is managed taking into account the specificity of the traumatic disease course.
      Hemorrhage and shock with gunshot PTW are determining the severity of patient's
      state and mortality in early period after trauma.

PMID- 11247422
TI  - [Treatment of fistula of abdominal part of the esophagus, stomach and duodenum].
AB  - The results of treatment of 142 patients with fistula of the abdominal esophagus,
      stomach and duodenum were analyzed. Tactic and principles of treatment of
      different types of the alimentary canal fistulas were elaborated. Mortality was
      31.7%.

PMID- 11247423
TI  - [Proteolytic activity of duodenal mucosa in elderly and senile patients in the
      presence of duodenal hemorrhage from ulcer].
AB  - During investigation of proteolisis of duodenum mucosa in patients of elderly and
      senile age with duodenal ulcer, complicated by hemorrhage, in terms up 8 for days
      there was revealed considerable increase of proteolytic activity, especially of
      high-molecular proteins and collagens, maximum--on the first day of hemorrhage.
      In all terms the revealed activity of anterior wall of duodenum was higher, than
      posterior.

PMID- 11247424
TI  - [Laparoscopic resection of the colon].
AB  - Possibilities of laparoscopic colonic resection and colectomy in the treatment of
      the patients with tumoral and nontumoral affection of colon and rectum were
      determined. Laparoscopic resection of colon and rectum was performed in 94
      patients, including 67--for colorectal cancer. Due to the disease recurrency 10
      patients died. Laparoscopic resection is the method of choice in the treatment of
      patients with nontumoral affection of colon.

PMID- 11247425
TI  - [Contemporary aspects of treatment of colonic cancer, complicated by ileus. Part
      III. Treatment of rectal cancer, complicated by ileus].
AB  - There were operated 331 patients with cancer of rectum, complicated by ileus.
      Radical operation was performed in 168 patients, palliative--in 57, symptomatic-
      in 106. Possibility of widening of evidences for performance of primary
      restorational, sphincter-preservational operations was proved.

PMID- 11247426
TI  - [Activity of the prostanoids system in inflammatory diseases of the colon].
AB  - Content of prostaglandins (PG) E2 and E2 alpha, prostacycline (PC) and tromboxane
      B2 (TxB2) in plasma of patient's blood with inflammatory diseases of large
      intestine was studied. In patients with nonspecific ulcerative colitis and
      Crohn's disease content of PGE2 is increased by 72.1%, PC--is decreased by 57%,
      TxB2--is increased by 144.8%. Detected changes have pathogenetic significance,
      their severity correlated with severity of the disease course. Tendency to
      normalization of the prostanoid system state was noted after performance of
      complex treatment.

PMID- 11247427
TI  - [Iatrogenic injury of biliary ducts during laparoscopic cholecystectomy].
AB  - Damage of biliary ducts (BD) during performance of laparoscopic cholecystectomy
      occurred in 24 (3.8%) of 635 patients. Damage of BD was identified in good time
      only in 4 (17%) observations. Noncorrected choledocholithialis and stenosis of
      major duodenal papilla sphincter were promoted by functioning of biliary fistula
      in 47% observations.

PMID- 11247428
TI  - [Diagnosis and surgical treatment of Mirizzi's syndrome].
AB  - Retrospective analysis was done concerning the course of cholelithic disease, the
      results of laboratory, ultrasonographic, radiological, endoscopical methods of
      investigation, conducted in 52 patients with different forms of Mirizzi syndrome.
      The method and extent of surgical correction of the disease are recommended.

PMID- 11247429
TI  - [Post-cholecystectomy syndrome in the era of laparoscopic cholecystectomy].
AB  - Functional disorders of gastric and intestinal motility as well as noncorrected
      residual or arised due to iatrogenic damage the biliary ducts pathology were the
      causes of postcholecystectomy syndrome occurrence after the laparoscopic
      cholecystectomy conduction.

PMID- 11247430
TI  - [Decompressive laparostomy as the method of choice in the treatment of the
      abdominal compression syndrome].
AB  - The experience of examination and treatment of 126 patients with severity trauma
      of abdomen was summarized. The performance of decompressive laparostomy in
      treatment of the abdominal compression syndrome was suggested. In 28 patients
      temporary closure of abdominal cavity by polychlorvinyl blend was applied.

PMID- 11247431
TI  - [Aspects of bile chemical contents in patients after cholecystectomy].
AB  - Chemical contents of bile was studied in 38 patients with cholelithic disease
      after conduction of cholecystectomy. It was established that in up to 4 weeks
      after the operation bile has lithogenic properties. It is expedient to do the
      bile reinfusion through the drain into duodenum to achieve its chemical contents
      normalization.

PMID- 11247432
TI  - [The treatment of postoperative abdominal hernia].
AB  - The results of treatment of 67 patients with postoperative abdominal hernia were
      analyzed. Approach to the choice of method and volume of operative intervention
      was proposed.

PMID- 11247433
TI  - [Diagnosis and treatment of embryonal hernia].
AB  - In 1994-1999 years in clinic 19 children with omphalocele were treated, 8 of them
      died. Authors proposed tactic of treatment of their own, giving preference to
      conservative method, what permitted to reduce mortality of children with
      embryonal hernia.

PMID- 11247434
TI  - [The drained blood reinflusion during knee and hip joint endoprosthetic surgery].
AB  - In 102 patients, to whom the total coxofemoral endoprosthesis was performed, and
      in 19--the knee joint endoprosthesis was done, reinfusion of blood, collected
      from the drain, was applied. The application of blood reinfusion have permitted
      to reduce quantity of the donor's blood applied or to escape it at all.

PMID- 11247435
TI  - [Radical cystectomy with ileoneocystoplasty].
AB  - There were examined 32 patients with cancer of bladder, to whom radical
      cystectomy with ileoneocystoplasty in the author's modification was performed.
      Operative intervention was done for the transitional cell carcinoma of bladder in
      T2-T4 stage. The method of the bladder formation using resection of the ileum
      segment 40-60 cm in length was adduced. The intestinal segment was transsected
      along the side opposite to mesentery, the transplant was placed in U-like
      fashion, the posterior wall of bladder was formed sewing together medial edges,
      anastomosis between bladder and ureter was performed. In 17 patients
      postoperative complications had occurred, mainly of septic-purulent character.
      Postoperative mortality was 9.4%. Radical cystectomy with ileoneocystoplasty is
      an effective method of medico-social rehabilitation of patients, which secures
      restoration of urodynamics of upper urinary ways and urination.

PMID- 11247436
TI  - [Estimation of the cerebral hemodynamics in patients with pathological kinking of
      arteries originated from the aortal arch according to angiography].
AB  - The state of cerebral blood flow was studied in 81 patients with chronic disorder
      of cerebral blood circulation using angiographic investigation. Various kinds of
      pathological kinking of the vessels, originated from the aortic arch, the
      reducing of their contrasting, the lowering of the blood flow velocity were
      disclosed. Enhancement of the capacity reserve of vascular channel while
      conducting the probe with sodium nitroprusside more than by 10% gave evidence
      about possibility of the blood flow restoration after reconstruction of the
      affected artery.

PMID- 11247438
TI  - [Pathomorphological aspects of the inflammatory process in soft tissues during
      the ozone application in the experiment].
AB  - In 35 white rats of Wistar line abscess of soft tissues was modelled. In animals
      of principle group influence of ozone-oxygenous gaseous mixture with
      concentration of ozone 0.1 mg/m3 times daily during 10 min were applied. While
      applicating ozone were noted reduction of exudative reaction and more rapid
      change of inflammatory phase, more early formation and maturation capsule around
      necrotic zone, than in control group, that promoted effective delineation of
      damage focus and enhancement of the inflammatory and dystrophic changes severity
      in tissues surrounding abscess.

PMID- 11247437
TI  - [Indices of lipid peroxidation and antioxidant defense system and prostanoid
      level in patients with uterine cancer].
AB  - The state of peroxydal oxidation of lipids, system of antioxidant defense and
      content of prostanoids in patients with cancer of the corpus uteri were
      investigated. Syndrome of endogenous intoxication with lowering of antioxidant
      potential and dysbalance of cyclic nucleotides and prostaglandines was
      established. The severity of above-cited disorders increased significantly after
      operation and during conduction of radiotherapy. This demanded administration of
      antioxidant and detoxicational therapy in complex of preoperative preparation.

PMID- 11247439
TI  - [Peripheric artery diseases. Systemic character of atherothrombosis needs a
      systemic approach to therapy].

PMID- 11247440
TI  - [Surgical treatment of intrathoracic compression of respiratory ways caused by
      the vascular ring anomaly in children].

PMID- 11247441
TI  - [Endogenic intoxication syndrome in appendicular peritonitis in children].

PMID- 11247442
TI  - [Application of preparation endotelon in complex treatment of chronic arterial
      insufficiency of lower extremities].
AB  - The results of treatment of 43 patients with chronic ischemia of extremities with
      application of preparation endotelon were summarized. Stable positive effect,
      preserved during 2-4 month was noted in 34 patients. Lowering of regional venous
      pressure, at average for the first week by (1.3 +/- 0.31) kPa, or (10 +/- 2.3) mm
      Hg, was observed after the first course of treatment conduction.

PMID- 11247444
TI  - [The restoration of colon continuity after the Hartmann surgery].
AB  - The operation of Duhamel for restoration of intestinal continuity after its
      obstructive resection for cancer of colon in 42 patients was applied.
      Postoperative complications had occurred in 16.7% patients, insufficiency of
      anastomotic sutures wasn't noted. Two (4.75%) patients with an acute
      cardiovascular insufficiency died.

PMID- 11247445
TI  - [Prophylaxis of the anastomotic sutures insufficiency in surgical treatment of
      complicated colonic cancer].
AB  - The existing methods of prophylaxis of the anastomosis sutures insufficiency
      (ASI) in surgical treatment of complicated colonic cancer (CC) were considered.
      High safety of the invagination anastomosis formation method, elaborated in the
      clinic, was shown. It was used in surgical intervention with primary restoration
      of intestinal continuity, which was performed in 379 patients with complicated
      CC. Postoperative complications had occurred in 89 (23.5%) patients, 35 (9.2%) of
      them died. Purulent-septic complications dominated in structure of postoperative
      complications, the ASI was noted in 4 (1.1%) patients.

PMID- 11247446
TI  - [The neuro-endocrinal system status in patients with severe inflammatory colonic
      diseases].
AB  - There were examined 27 patients with inflammatory diseases of colon. In cases of
      the nonspecific ulcerative colitis and Crohn's disease of colon the thyroid gland
      insufficiency occurs in variant of the thriiodinethyronine low contents syndrome,
      causing the necessity of the substitution therapy conduction in postoperative
      period.

PMID- 11247447
TI  - [Operative treatment of complicated duodenal and pyloric ulcer disease].
AB  - There were examined 135 patients with perforative ulcer of the gastric terminal
      portion (GTP) and of duodenum. Performance of duodeno- or gastroduodenoplasty
      without vagotomy, the correcting therapy conduction in early postoperative period
      had promoted the normalization of the GTP motor function and the gastric acid
      output reduction in late follow-up period, trusting the expediency of organ
      preserving operation conduction without vagotomy as radical method of the
      complicated ulcer disease treatment.

PMID- 11247443
TI  - [Early extubation of children in the the first year of life with inborn heart
      failure after surgery, performed with artificial blood circulation].
AB  - The possibility of early extubation of the first year of life children after
      surgical correction of congenital heart diseases while artificial blood
      circulation conduction was studied. For the 1996-1999 period surgical treatment
      was conducted in 381 patients aged at average (5.71 +/- 3.17) month, body mass at
      average (5.77 +/- 1.8) kg. 163 (42.7%) patients were converted to independent
      respiration in 6-12 hours after operation, satisfactory clinical state and
      indexes of gas exchange were in 122 (74.8%), 8 patients needed reintubation.
      Early extubation permit to reduce of respiratory complications frequency,
      duration of treatment in intensive therapy unit.

PMID- 11247448
TI  - [Diagnostic and prognostic significance of the blood neutrophils functional
      activity in patients with an acute destructive pancreatitis].
AB  - The neutrophils functional state was studied in 101 patients with an acute
      destructive pancreatitis (DP), complicated by parapancreatitis, in 20 patients
      with edematic pancreatitis and in 25 healthy persons using cytochemical reactions
      with determination of the enzymes activity of alkaline phosphatase,
      myeloperoxidase, and also of lysosomic-cation proteins, phospholipids and
      glycogen. The enzymatic contents of neutrophils changes in acute period of
      destructive pancreatitis (DP) are causing their function inhibition, promoting
      the infection complications occurrence. The neutrophils functional activity
      indexes may be used in early diagnosis and prognostication of the DP course.

PMID- 11247449
TI  - [Surgical treatment of an acute destructive pancreatitis using laparoscopy and
      peritoneal dialysis].
AB  - Laparoscopic intervention was performed in early stages of acute destructive
      pancreatitis in 34 patients. In 23 patients after draining of the abdominal
      cavity the laparoscopic intermitting peritoneal dialysis with application of the
      "Gambro" firm solutions during 2-4 days was done. Efficacy of the proposed method
      of detoxication in complex treatment of patients was established.

PMID- 11247450
TI  - [The anti-hypoxic agent influence on the early postoperative period course in
      patients with peritonitis].
AB  - In 70 patients with diffuse peritonitis, occurred in early postoperative period,
      preparation lipine was included in complex of treatment, promoting the results of
      treatment improvement.

PMID- 11247452
TI  - [The anatomy of coronary arteries in the main vascular transposition].
AB  - The analysis of the coronary arteries (CA) morphology in the main vessels
      transposition (MVT) cases was presented, basing on the clinical and cadaveric
      investigations data. During performance of 88 operations there were revealed 8
      different morphological variants of the CA branching. There were studied 8 heart
      macropreparations with MVT and there were disclosed 4 different types of the CA
      morphology.

PMID- 11247451
TI  - [The first experience of application of photo-modified erythrocytes for the
      treatment of the chronic arterial ischemia syndrome].
AB  - Efficacy of application of intraarterial erythrocytes infusion, photomodified by
      using low-energy laser irradiation, was proved, basing on comparative analysis of
      treatment results of the different groups of patients with obliterating disease
      of the lower extremities vessels.

PMID- 11247453
TI  - [Surgical treatment of chronic ischemia of upper extremities].
AB  - In 300 patients with chronic disorder of the upper extremities blood circulation
      725 operative interventions were performed. Application of differentiated
      approach to the choice of the surgical correction method had allowed the positive
      result achievement in late follow up period in 77.8% patients.

PMID- 11247454
TI  - [Surgical treatment of recurrence of the varicose veins in the lower
      extremities].
AB  - The results of treatment in 1080 patients with the lower extremities varicose
      disease (VD) were analyzed. For the subcutaneous veins recurrent varicose (SVV)
      there were operated 11.2% patients, including, once--76.1%, twice--17.4%, three
      times--6.5%. In all 146 the operations were performed. Sclerosing therapy of SVV
      was applied in 21 patients. Basic mistake during performance of the first
      operative intervention for the VD was insufficient evaluation of character of the
      blood outflow disorder.

PMID- 11247455
TI  - [The ATP, phosphoenolpyruvate contents and the hexokinase activity in
      erythrocytes in injured persons with the pulmonary gun shot wound].
AB  - The adenosine triphosphate and phosphoenolpyruvate contents in erythrocytes are
      enhancing before and in early terms after the operation for the gunshot lungs
      parenchyma damage. The study of molecular mechanisms of the lungs pathology
      allows to evaluate the severity of their damage, to substantiate the operative
      treatment tactic and the medicinal therapy principles.

PMID- 11247456
TI  - [The pulmonary microangiopathy in patients with tuberculosis coexisting with
      diabetes mellitus].
AB  - There were done histologic, electron-microscopic investigations of the lungs
      preparations in 47 patients with destructive tuberculosis (DT) and diabetes
      mellitus, the operations were performed, the signs of the disseminated
      microangiopathy were revealed. This complication negatively influence the DT
      course before and after the operation, and the final result of operation also.

PMID- 11247457
TI  - [Treatment and monitoring of patients with differentiated cancer of thyroid
      gland].
AB  - There were examined 200 patients aged from 19 to 77 years with differentiated
      cancer of the thyroid gland (TG). The combined treatment, which included
      performance of operation, radioiodine therapy and hormonotherapy, was conducted
      to all the patients. Total and maximum subtotal TG resection was performed in 90%
      patients, nonradical operation--in 10%, 23% patients were reoperated.
      Postoperative monitoring according to chart was done with application of dynamic
      scintigraphy and determination of the thyroglobuline level in the blood serum.
      The TG residual tissue (RT) was revealed in 61% patients and in 39%--the cancer
      metastases in the lymphatic nodes. RT of TG was eliminated in 86.8% patients
      after the first radioiodine therapy course conduction in middle remedial activity
      (2.79 +/- 0.11) GBq, the metastases devitalization--in 67.9% in middle remedial
      activity (4.07 +/- 0.12) GBq.

PMID- 11247458
TI  - [The surgical choice strategies in the treatment of femoral bone fractures in
      injured persons with combined trauma].
AB  - In 1990-1999 years osteosynthesis of the hip bone was performed in 500 injured
      persons with combined trauma. In 63.1% patients the plates were used, in 19.6%-
      pivots, in 17.3%--apparatuses of external fixation. The choice of the method and
      optimal terms of performance of the surgical stabilization procedure of fracture
      were determined by the trauma severity in accordance with anatomo-functional
      model. In 12-18 months after the operation 198 patients were examined. Good
      result was noted in 79.6% of patients, satisfactory--in 17.3%, bad--in 3.1%.

PMID- 11247459
TI  - [Operative correction of deformity of the foot posterior part].
AB  - The results of operative treatment of 29 patients with the posterior part of foot
      deformity were analyzed. There were applied the heel bone osteotomy according to
      Dwyer and Evans, subastragalar and triple arthrodesis. The result of treatment in
      terms from 10 months to 12 years was evaluated as good--in 19 patients, fair--in
      10, bad--in 2. Application of internal fixation and osseous autoplasty had
      promoted the achievement of better results of treatment.

PMID- 11247461
TI  - [The dynamics of the tissue blood flow changes of the oxygen pressure and of the
      vessels reactivity in non-damaged hepatic tissue in mechanical trauma].
AB  - The mechanical hepatic trauma was simulated in experiment on dogs. Long local
      blood flow reduction, the oxygen pressure lowering in nonaffected hepatic tissue
      and organic blood flow in kidney as well were noted while the 34.2% hepatic mass
      injury with 10.58% blood loss. The magnitude of the vessels reactivity
      coefficient of these organs is reducing in 30 min and 1 hour after the hepatic
      injury occurrence and then changes in untrustworthy manner.

PMID- 11247460
TI  - [Endoprosthesis in patients with dysplastic coxarthrosis or in those who suffered
      Perthes' disease in childhood].
AB  - Endoprosthesis of the hip joint was performed in 48 patients with coxarthrosis
      aged 40-50 years, which had occurred after the Perthes's disease. The non-cement
      fixing of the Ver Sys endoprosthesis was applied, osteotomy and bringing down of
      the greater trochanter were done in 33% of observations simultaneously or 3-6
      months before doing the endoprosthesis.

PMID- 11247462
TI  - [Modern trends in the treatment of the obturated colonic ileus].
AB  - The results of treatment of 365 patients with obturated colonic ileus, caused by
      tumor, for the period from 1979 to 2000 years were analyzed. Till 1987 year in
      clinic were applied proximal colostomy, excision of tumor, restorative stage--in
      3-4 months. From 1987 year using the method of intraoperative colonic lavage we
      performed simultaneous intervention with formation of primary anastomosis.

PMID- 11247463
TI  - [Verification of diagnosis of the gastric ulcer malignant degeneration].

PMID- 11247464
TI  - [Cystic transformation of biliary ducts].

PMID- 11247465
TI  - [Surgical treatment of colonic cancer in young patients].

PMID- 11247466
TI  - [Comparative estimation of the myocardium functional reserves in patients with
      combined atherosclerotic affection of arteries].

PMID- 11247467
TI  - [ The shortened antibacterial therapy course during Helicobacter infection
      treatment with clacid].

PMID- 11247468
TI  - [Observation of spontaneous rupture syndrome].

PMID- 11247469
TI  - [The preoperative diagnosis and treatment peculiarities of patients with pharyngo
      facial myasthenia].

PMID- 11247470
TI  - [Performance of the programmed revision of the hip stump after the lower
      extremity amputation conduction].

PMID- 11247471
TI  - [Long-term stay of foreign body in abdominal cavity].

PMID- 11247472
TI  - [Prophylaxis and treatment of eventration].

PMID- 11247473
TI  - [Improvement of the surgical treatment results of patients with an acute ileus].
AB  - The results of surgical treatment of 339 patients with an acute ileus (AI) were
      analyzed. Severe disorders of water-electrolytic, protein metabolism and immune
      status in 62 patients were revealed. Method of treatment of functional
      postoperative AI with application of serotonin adipinate was proposed.

PMID- 11247474
TI  - [Surgical treatment of gastroesophageal reflux disease in the presence of
      coexistent hiatal hernia].
AB  - Experience of treatment of coexistent hiatal hernia (HH) and gastroesophageal
      reflux disease (GERD) in 491 patients using simultant hernioplastic and
      antireflux operation was summarized. Complete fundoplication was performed in 478
      (97.4%) patients, noncomplete one--in 13 (2.6%), cruroraphy--in 321 (65.4%),
      including complex method of hernioplasty--in 80 (16.3%). Postoperative mortality
      was 0.8% (4 patients). The tactical and methodical principles applied have
      permitted to guarantee the physiologicity and safety of the coexistent HH and
      GERD surgical treatment.

PMID- 11247475
TI  - [Chronic pancreatitis].
AB  - Performance of complex examination using endoscopic pancreatography permitted to
      study the pancreatic ductal system state, disorder of which constitutes an
      objective criterion in diagnosis of chronic pancreatitis and in the choice of
      optimal volume of operative intervention.

PMID- 11247476
TI  - [Prophylaxis of cardiovascular and respiratory complications after conduction of
      cholecystectomy in elderly and senile patients].
AB  - Surgical treatment of calculous cholecystitis was done in 150 elderly and senile
      patients. Open intervention was applied in 60 patients, laparoscopic
      cholecystectomy (LCHE)--in 90, of them in 30--using epidural anesthesy. The LCHE
      performance in combination with epidural anesthesy reduces the risk of occurrence
      of vascular and respiratory complications in elderly and senile patients.

PMID- 11247477
TI  - [Application of auxiliary manipulation channel during performance of
      cholecystectomy using minimal access].
AB  - The conduction of the supportive manipulation channel (SMCH) during the
      cholecystectomy and the oblique-changing gall bladder puncture performance was
      proposed to improve the conditions for doing the operation, rational application
      of minimal oblique subcostal access (MOSA) and postoperative complications
      prophylaxis. There were operated 17 patients using MOSA, in 15 SMCH was
      conducted, including 2 with intervention on extrahepatic biliary ducts:
      choledocholithotomy with external draining of common biliary ducts. In 12
      patients intradermal suture was done.

PMID- 11247478
TI  - [Ultrasonic duplex scanning in occlusion of abdominal aorta, arteries of iliac
      segment and of lower extremities].
AB  - The regional hemodynamics peculiarities were studied in patients with various
      types of occlusive-stenotic affection of abdominal aorta and iliac arteries,
      using ultrasonic duplex scanning. The character of the blood flow peculiarity
      along main arteries and collateral branches was determined depending on the
      affection level. The quantitative indexes of blood flow along the most
      significant collaterals were studied as well as their role in the compensation
      process of the disordered distal blood flow.

PMID- 11247479
TI  - [Hemodynamic correction of the main vascular transposition].
AB  - From 1992 till 2000 yr 70 patients were operated on in the clinic for the main
      vessels transposition (MVT) using method of Senning. In the principal group 53
      patients were incorporated suffering MVT with unchanged interventricular septum
      (IVS) and with its minimal defect as well. The IVS defect and concurrent
      anomalies were revealed in 17 patients. Hospital mortality was 38.4%. In the 3.8
      yrs follow-up period at average all the patients were alive, in majority of them
      satisfactory function of right systemic ventriculus was noted.

PMID- 11247480
TI  - [Strategies of surgical treatment of gastroesophageal reflux disease].
AB  - The improved surgical tactics for gastroesophageal reflux disease was applied in
      treatment of 706 patients with all stages, popular forms and complications. The
      tactics was based on principles, concerning the selection of patients for
      operative treatment, taking into account specific indications and
      contraindications for its performance and methods of the intervention choice.

PMID- 11247481
TI  - [The usage of the laser induced fluorescence in laparoscopy].
AB  - Optic biopsy (the laser-induced fluorescence) was applied in laparoscopic surgery
      in 14 patients with colonic malignancy. There were investigated 66 lymph nodes.
      Trustworthiness of the laser induced fluorescence was 80.7%.

PMID- 11247482
TI  - [Intensive therapy and strategy of management of patients with rectal cancer
      after the colonic descending to the perineum].
AB  - Optimal tactic for management of the patients on various stages of treatment was
      elaborated together with surgical procedure, basing on the experience of 3500
      operations conduction for cancer recti, mainly abdominal resection with colon
      descendant to perineum. Methods of preoperative preparation and anesthesiological
      support were stated as well as the tactics of postoperative management of
      patients.

PMID- 11247483
TI  - [The ways of the efficacy raising in surgical treatment of patients with colonic
      cancer].
AB  - The indications extension for the radical surgical intervention conduction in
      elderly and senile patients and with locally spreading colonic cancer had
      promoted the result of their treatment improvement.

PMID- 11247484
TI  - [The Helicobacter pylori role in origination of hemorrhage in elderly and senile
      patients with duodenal ulcer disease].
AB  - During examination of 37 patients with duodenal ulcer disease aging more than 60
      years it was established that while presence of the ulcer complicated by bleeding
      the revelation frequency of Helicobacter pylori (HP) in gastric antrum is
      increasing up to 74% and in cases of noncomplicated ulcer--70%. HP was revealed
      most frequently in patients with "senile" ulcer. For an "inveterate" ulcer the
      presence of S-like forms is typical. The absence of HP in 41.6% patients with
      "senile" ulcer testifies the presence of other mechanisms of occurrence and
      support of bleeding.

PMID- 11247485
TI  - [Complications after conduction of hemorrhoidectomy].
AB  - The results of examination of 724 patients after hemorrhoidectomy conduction were
      analyzed. In term from 6 month to 7 years in 172 patients the diseases of colon
      and rectum occurred. While the immunologic investigation conduction in them the
      secondary immune deficient state was noted, causing the purulent-inflammatory
      complications and other postoperative disorders origination.

PMID- 11247487
TI  - [Application of aortocoronary shunting in patients with ischemic heart disease
      and congestive heart failure].
AB  - In 280 patients with an ischemic heart disease and congestive heart failure the
      aortocoronary shunting was performed. While doing the heart catheterization there
      was established complete overlap or significant stricture of 3.9 coronary
      arteries or branches at average per one patient. Selective operation was done in
      242 (86%) patients, urgent--in 28 (10%), reoperation--in 10 (3.6%). Operative
      mortality was 2.5% (7 patients died).

PMID- 11247486
TI  - [Reconstructive reoperations on abdominal aorta and main arteries of extremities
      in the synthetic prosthesis thrombosis].
AB  - The results of surgical treatment of 176 patients aging from 42 to 75 years, to
      whom earlier the reconstruction operation on abdominal aorta and the lower
      extremities main arteries was performed, were analyzed. The causes of the
      synthetic prosthesis thrombosis occurrence were studied, individualized surgical
      tactics, depending on the hip arteries inflow and outflow, was substantiated.
      There was proposed an access to a. femoris profunda and the profundoplasty
      method. The immediate and late follow-up results of their application are
      satisfactory.

PMID- 11247488
TI  - [Origination of mediastinal hernia in late follow up period after performance of
      pulmonectomy].
AB  - In 25-40 years after pneumonectomy conduction the mediastinal hernia (MH)
      occurred in 62.4% of 210 patients. Principal clinico-radiological signs of MH
      were vicarious hypertrophy and true pulmonary emphysema. Vicarious hypertrophy of
      single lung is forming, as a rule, in patients, operated on in childhood, is
      characterized by favourable clinical course and constitutes the MH compensated
      stage.

PMID- 11247489
TI  - [Application of xeno-spleen in treatment of purulent-septic complication].
AB  - In 22 patients with purulent-septic complications the extracorporal attaching of
      the xenolien cryopreserved sections was applied together with conventional
      therapy. Distinct reduction of the endogenic intoxication severity an the immune
      state of patients normalization were noted.

PMID- 11247490
TI  - [Changes of the glycemia level in surgical treatment of purulent-necrotic
      affection of the foot in patients with diabetes mellitus].
AB  - Of 266 patients with diabetes mellitus (DM) 240 were operated on for purulent
      necrotic affection of foot. The carbohydrate metabolism state before the
      operation and the postoperative course of DM do not influence the surgical
      intervention volume and the operative wound healing. The glycemia level exceeding
      11 mmol/l 3 days after the operation trusts the nonviability of the tissues
      resided and the need for reoperation.

PMID- 11247491
TI  - [Application of the color Doppler scanning in dynamic follow up after the
      operation on thyroid gland].
AB  - After conduction of operation on thyroid gland (TG) 35 patients were examined
      using color Doppler mapping. The TG stump blood supply was determined mainly
      along periphery in sites of newly created membranes. Maximal rate of the TG
      tissue growth was observed in 1 year. The changes of the structure type can not
      be used as the test for establishing of the "goiter recurrency" diagnosis.

PMID- 11247493
TI  - [Application of the compression biliary-digestive anastomosis in surgical
      treatment of the biliary ducts obstruction].
AB  - The methods of formation and the surgical instruments for the biliodigestive
      compression anastomoses (BDA) doing were elaborated in the clinic. For the 1997
      2000 years period 137 patients were operated on for the biliary ducts
      impassibility, in 36 of whom the compression BDA was formated. In 69% patients
      the rejection was noted on 7-10th day after the operation. The result of
      treatment was studied in 6 month-4 years term and estimated as good in 32
      (94.12%) patients.

PMID- 11247492
TI  - [Radical nephrectomy for the kidney tumor with the thrombus invading vena cava
      inferior].
AB  - The results of treatment were analyzed in 92 patients with the kidney tumor in
      whom the thrombus invasion into vena cava inferior was revealed. Ultrasonographic
      scanning and magnetic resonance tomography were most informative methods in the
      diagnosis. The staging of the tumoral thrombus invasion was elaborated depending
      on which the surgical tactics was choosen. The procedure technique was depicted
      and the operations schemes were adduced. The vena cava thrombectomy performance
      is absolutely indicated in patients without metastases in lymph nodes and distant
      organs. The five-year survival index for this patients was 55-60%.

PMID- 11247495
TI  - [Surgical treatment of destructive pancreatitis].

PMID- 11247494
TI  - [The influence of the combined treatment on the energy metabolism in patients
      with the uterine cancer].
AB  - The experience of management of the patients with cancer of the uterus body was
      summarized to improve the results of combined (surgical and radiation) treatment.
      The essential initial disorders of the power supply metabolism, keeping worsening
      after the operation, were revealed. The conduction of the immune correction
      therapy in complex of preoperative preparation with individual selection of the
      immune preparations using the tests in vitro had promoted the postoperative
      period course improvement, the frequency of complications reduction, the
      stabilization and tendency for the power supply metabolism restoration after the
      operation and further during the radiation therapy conduction.

PMID- 11247496
TI  - [Observation of the vena cava inferior damage while performing laparoscopic
      cholecystectomy].

PMID- 11247498
TI  - [Computer and ultrasonic diagnosis of destructive pancreatitis].
AB  - During investigation of 118 patients with destructive pancreatitis using
      ultrasonographic investigation and computeric tomography the signs of
      pancreonecrosis and retroperitoneal phlegmon were revealed correlating with
      origination of methane and enhancement of its concentration in blood, trusting
      the pancreatic tissue structural and functional insufficiency occurrence.

PMID- 11247497
TI  - [Performance of segmental vein surgery in patients with acute thrombophlebitis of
      the varicose veins of the lower extremities].

PMID- 11247500
TI  - [Typological characteristics of energy supply to muscles of racing skiers].

PMID- 11247499
TI  - [Functional body capacity under conditions of various carbon dioxide and oxygen
      ratios].

PMID- 11247501
TI  - [Typical responses of the immune system in pathological processes].

PMID- 11247502
TI  - [Correlations between the leukocyte number and their volume distribution
      parameters in humans].

PMID- 11247503
TI  - [Principles of physiological regulation of body functions in incomplete
      adaptation].

PMID- 11247504
TI  - [New stage in the immunogram technique--visual streptavidin-biotin method].

PMID- 11247505
TI  - [Human log-latency auditory evoked potentials during radial motion of the source
      of sound].

PMID- 11247506
TI  - [Peripheral blood parameters in humans under low temperature conditions in the
      far North].

PMID- 11247507
TI  - [Various indices of the health status of school children in a big city depending
      of their life style].

PMID- 11247508
TI  - [Dynamic mapping of temperature fields of the human brain].

PMID- 11247509
TI  - [Functional brain asymmetry and principles of analysis of lexical and grammatical
      material].

PMID- 11247510
TI  - [Dynamics of the adolescent EEG parameters and changes in the CNS functional
      state (relaxation) caused by rhythmic acoustic stimulation].

PMID- 11247511
TI  - [Perception of the emotional speech component against a noise background by
      stuttering children. Communication II. Analysis of temporal characteristics of
      recognition of various emotions].

PMID- 11247512
TI  - [Neurophysiological correlates of changed mental state in labor. Communication I.
      EEG characteristics].

PMID- 11247513
TI  - [EEG correlates of mild impairments in higher cortical functions].

PMID- 11247515
TI  - [Physiological mechanisms of homeostasis in stress in humans].

PMID- 11247514
TI  - [The neuropeptide compensation for impared brain functions in the ascending row
      of mammals: interaction between the nervous and immune systems].

PMID- 11247516
TI  - [Effects of climate in the arid region on the human hormonal status].

PMID- 11247517
TI  - [Forecast of the health status, physical work capacity, and professional success
      under arid zone conditions].

PMID- 11247518
TI  - [Effect of argon on oxygen consumption during physical load under hypoxic
      conditions in humans].

PMID- 11247519
TI  - Frequently asked questions ... again.

PMID- 11247520
TI  - Living in a house of cards: family experiences with long-term childhood
      technology dependence.
AB  - Families' experiences of providing long-term home care for the child who is
      technology dependent were explored via parental interviews. Families identified
      frequent change, uncertainty, and unpredictability in their lives, a phenomenon
      described as "living in a house of cards." Attempts to increase stability
      involved the use of vigilance, advocacy, and reframing. Areas of challenge,
      change, and growth included making sense of life, managing daily life with
      technology, and maintaining a functioning family. Increased understanding of
      family experiences with long-term childhood technology dependence can provide
      nurses with additional strategies for providing optimal care to this population.

PMID- 11247521
TI  - The infant with Pierre Robin sequence: review and implications for nursing
      practice.
AB  - Pierre Robin sequence (PRS) is associated with long-term respiratory,
      nutritional, and developmental difficulties. Hypoxic complications, including
      cerebral impairment, cor pulmonale, and failure to thrive may be prevented or
      minimized with early detection and comprehensive care. This article reviews the
      embryological development of PRS and outlines the medical and nursing
      implications for treatment. Partnership with parents and a coordinated community
      care team are essential for successful management of infants and children with
      PRS.

PMID- 11247522
TI  - Measuring parental uncertainty during the diagnosis phase of serious illness in a
      child.
AB  - The purpose of this study was to revise and evaluate the Parental Perception of
      Uncertainty Scale (PPUS) for use in measuring parental uncertainty during the
      diagnosis of serious illness in a child. The concept of parental uncertainty
      during diagnosis was elaborated and original PPUS items were revised based on a
      review of the literature. Content validity of the revision was judged by nurse
      and parent experts. Preliminary psychometric evaluation of the measure was
      conducted in a sample of 25 biological mothers of infants who are HIV
      seropositive. The results offer initial support for the reliability and validity
      of the revised instrument.

PMID- 11247523
TI  - Self-esteem and hopefulness in adolescents with cancer.
AB  - Increased survivorship in childhood cancer has raised questions about
      adolescents' psychosocial functioning during the treatment experience and long
      term adaptation as cancer survivors. This descriptive correlation study examines
      the relationships among the stages of adolescence, gender, self-esteem, and
      hopefulness in a sample of 45 adolescents with cancer. The perceived level of
      self-esteem was measured by using the Coopersmith Self-Esteem Inventory; the
      amount of hopefulness was measured by using the Hopefulness Scale for
      Adolescents. Mean scores for self-esteem and hopefulness were comparable to
      normative data reported for healthy adolescents on each scale. Perceived level of
      self-esteem and hopefulness did not significantly differ between boys and girls
      overall; early, middle, and late adolescents; or between boys and girls within
      each stage of adolescence. A stepwise multiple regression analysis showed self
      esteem and the early stage of adolescence accounted for 27.3% (R2 = .306) of the
      variance in hopefulness scores. Self-esteem was the most significant predictor (F
      = 12.456, p = .001), explaining 20.7% of the variance (R2 = .225, p = .001). This
      study contributes to nursing the knowledge of the psychosocial response and the
      treatment experience in adolescents with cancer. These results can be used in
      future research to develop and test nursing actions that can influence a
      perceived sense of self-esteem and hopefulness and potentially allow for
      continued psychosocial development and effective coping among these adolescents
      during treatment and into survivorship.

PMID- 11247525
TI  - Improving adolescent parent-infant interactions: a pilot study.
AB  - The study objective was to pilot test Keys to Caregiving, a program designed to
      improve interactions and contingent responsiveness between adolescent mothers and
      their infants. First-time adolescent parents, aged 15 to 19 years, received
      either the Keys to Caregiving program delivered by 6-weekly visits or a control
      program consisting of 6-weekly neutral visits. Parent-infant interactions and
      contingent responsiveness during teaching and feeding, and infant cognitive
      development were assessed when infants completed the program. The results suggest
      that the Keys to Caregiving program shows promise as a method of improving
      adolescent mothers' interactions with their infants.

PMID- 11247524
TI  - Adolescent research recruitment issues and strategies: application in a rural
      school setting.
AB  - This report discusses adolescent research recruitment strategies in general and
      specifically, those developed by a research team for a rural school setting.
      Recruitment of adolescent subjects involves the consideration of several complex
      issues. These issues include adolescent development, ethical and legal
      guidelines, and access to school settings. Specific strategies are discussed
      regarding access and culture of the rural setting, collaboration, and recruitment
      procedures in relation to their use to recruit adolescent subjects from rural
      schools.

PMID- 11247527
TI  - Children and puberty.

PMID- 11247526
TI  - Health insurance programs for children.

PMID- 11247529
TI  - Continuing nursing care needs of children at time of discharge from one regional
      medical center in Sweden.
AB  - Hospital nurses used an investigator designed survey instrument to record
      demographics and anticipated nursing needs of 29 children discharged from 7 units
      during a 1 month period. The median age of the children was 18 months and 77% of
      the sick children had one or more siblings. Parental leave enabled most parents
      to participate in the child's hospital care. Over three quarters of the families
      reported no support person available to assist them at home. At time of discharge
      42% of the children required long-term nursing interventions related to chronic
      illness. Nurses trained parents visiting in the hospital for an average of 3
      hours and 40 minutes per family before discharge. Nurses also arranged an
      informal system of follow-up telephone contact but few community referrals. With
      decreasing length of hospital stay, parents need a formal system of nursing
      support before and after the discharge of their child from a hospital.

PMID- 11247528
TI  - The sanctity of death.

PMID- 11247531
TI  - Development of a profitable procedure for the extraction of 2-H-1-benzopyran-2
      one (coumarin) from Mikania glomerata.
AB  - This report deals with a new procedure suitable for the extraction of coumarin 1
      from Mikania glomerata. The aim of this investigation is to obtain this compound
      in an economically profitable way, taking into account the yield of its
      extraction, the cost, and the time of the overall process. Fresh and dried plants
      collected in several areas of the State of Rio de Janeiro were used, and seasonal
      effects on coumarin content were studied. Obtained results indicated that
      extraction with a 1% (w/v) NaOH solution, under appropriate conditions, allows a
      simple and complete recovery of the desired product and that the best yields were
      obtained with the fresh aerial parts of the plant. Season and area of harvesting
      effects have also been studied.

PMID- 11247530
TI  - Polymeric controlled drug-delivery systems: perspective issues and opportunities.
AB  - Although, the drug-delivery system (DDS) concept is not new, great progress has
      been made recently in the treatment of a variety of diseases. Targeting delivery
      of drugs to the diseased lesions is one of the most important aspects of DDS. To
      convey a sufficient dose of drug to the lesion, suitable carriers of drugs are
      needed. Polymers, which swell and contract in response to external pH levels, are
      being explored. The research in this area is being carried out all over the world
      at a great pace. Not only that new developments are emerging in the existing
      technologies, but also various new technologies are being developed and tested.
      Consequently, a huge amount of new information is available, which should be
      compiled and presented in a comprehensive way to benefit large numbers of users
      in this area as well as to help active research workers in the field. The purpose
      of this review is to discuss some recent advances and future prospects in
      controlled drug-delivery technology. The article serves as a useful tool for the
      beginners as well as for the researchers actively involved in this fascinating
      area of applied polymer science.

PMID- 11247532
TI  - Determination of the aqueous solubility of drugs using a convenient 96-well plate
      based assay.

PMID- 11247533
TI  - Characterizing colloidal structures of pseudoternary phase diagrams formed by
      oil/water/amphiphile systems.
AB  - Two pseudoternary phase diagrams were constructed using ethyl oleate, water, and
      a surfactant blend containing poly (oxyethylene 20) sorbitan monooleate and
      sorbitan monolaurate with or without the cosurfactant 1-butanol. Two colloidal
      regions were identified in the cosurfactant-free phase diagram; a microemulsion
      (ME) and a region containing lamellar liquid crystals (LC). The addition of 1
      butanol increased the area in which systems formed microemulsions and eliminated
      the formation of any liquid crystalline phases. Samples that form the colloidal
      regions of both systems were investigated by freeze-fracture transmission
      electron microscopy and by viscosity and conductivity measurements. The three
      techniques were compared and evaluated as characterisation tools for such
      colloidal systems and also to identify transitions between the colloidal systems
      formed. A droplet ME was present at a low water volume fraction (phi w) in both
      systems (phi w < 0.15) as revealed by electron microscopy. At higher phi w
      values, LC structures were observed in micrographs of samples taken from the
      cosurfactant-free system while the structure of samples from the cosurfactant
      containing system was that of a bicontinuous ME. The viscosity of both systems
      increased with increasing phi w to 0.15 and flow was Newtonian. However,
      formation of LC in the cosurfactant-free system resulted in a dramatic increase
      in viscosity that was dependent on phi w and a change to pseudoplastic flow. In
      contrast, the viscosity of the bicontinuous ME was independent of phi w. Three
      different methods were used to estimate the percolation threshold from the
      conductivity data for the cosurfactant-containing system. The use of nonlinear
      curve fitting was found to be most useful yielding a value close to 0.15 for the
      phi w.

PMID- 11247534
TI  - High-performance liquid chromatography assay for indorenate in pharmaceutical
      powders.
AB  - A high-performance liquid chromatographic (HPLC) method for quantification of
      indorenate admixed of pharmaceutical excipients (Pharmatose DCL 21, Povidone USP
      and Helmcel 200) is described. Indorenate was extracted from the mixtures using a
      mobile phase composed of acetonitrile and a sodium acetate buffer solution 0.1 M
      (63:37) and separated from other dissolved components by ion supression-HPLC. The
      method was standardized using a C-18 column (250 mm x 4.8 mm, i.d., 5 microns).
      The photometric detector was fixed at 228 or 272 nm depending on the admixed
      excipients. Validation parameters included linearity, precision, accuracy,
      reproducibility, and specificity. The method was specific, selective, and capable
      to distinguish indorenate from their degradation products and the
      antihypertensive pelanserine.

PMID- 11247535
TI  - Using experimental design to optimize the process parameters in fluidized bed
      granulation.
AB  - In this study many parameters were screened for a small-scale granulation process
      for their effect on the yield of granules between 75 and 500 microns and the
      geometrical granule mean size (d50). First a Plackett-Burman design was applied
      to screen the inlet air temperature, the inlet flow rate, the spray rate, the
      nozzle air pressure, the nozzle spray diameter, and the nozzle position. The
      Plackett-Burman design showed that the key process parameters were the inlet flow
      rate and the spray rate and probably also the inlet air temperature. Afterward a
      fractional factorial design (2(5-2)) was applied to screen the remaining
      parameters plus the nozzle aircap position and the spraying time interval. The
      fractional factorial design showed that the nozzle air pressure was also
      important. As the target values for the granule yield (between 75 and 500
      microns) and the geometric mean granule size (between 300 and 500 microns) were
      reached during the screening experiments, further optimization was not considered
      necessary.

PMID- 11247536
TI  - Effect of urea and pantothenol on the permeation of progesterone through excised
      rat skin from polymer matrix systems.
AB  - Standard in vitro permeation experiments, using excised rat skin, were carried
      out to establish the release profile and permeation behavior of progesterone from
      polymethacrylate (PMA), polyvinylpyrrolidon (PVP), and polyvinylalcohol (PVA)
      transdermal systems. Data obtained show significant differences in release
      characteristics from each polymer systems. The greatest amount of progesterone
      was released from the PVA system. The influence of urea and pantothenol on
      progesterone release was also investigated. Release data were compared with the
      permeation rates of progesterone across excised rat skin. The highest permeation
      rates were measured from PVA matrices containing 5% urea (860 +/- 138
      micrograms/cm2; cumulative amount permeated in 24 hr) and from PVP matrices
      containing 6% pantothenol (660 +/- 73 micrograms/cm2; cumulative amount permeated
      in 24 hr). A good correlation between release and permeation data was found with
      the polymer matrices; however, this was not the case when additives were
      included.

PMID- 11247538
TI  - Influence of water on the solubility of two steroid drugs in hydrofluoroalkane
      (HFA) propellants.
AB  - The objective of this research work was to investigate the influence of water
      level, temperature, and propellant composition on the solubility of two
      hydrophobic steroid drugs, triamcinolone acetonide (TAA) and beclomethasone
      diapropionate (BDP). pMDIs containing TAA or BDP, spiked water, and propellant
      blend with different ratios of HFA 134a and HFA 227 were prepared. The contents
      of the prepared pMDIs were filtered through a 0.22 mm Acrodisc, syringe filter
      into a receiving canister after the pMDIs were equilibrated at 15 degrees C, 25
      degrees C, 30 degrees C, and 40 degrees C. The drug concentration in the
      receiving canisters was determined by HPLC and the drug solubility in the
      propellant blend was calculated. Also, the drug crystal collected on the filter
      from the donor pMDIs were characterized by x-ray diffraction. The solubility of
      TAA and BDP varied with propellant composition at all experimental temperatures
      investigated. The solubility of TAA and BDP increased as the temperature was
      increased at all propellant compositions and water levels studied, but decreased
      as the water level in the propellant system was increased at all compositions and
      temperatures. The x-ray diffraction results indicated that the water in the
      propellant system had no significant influence on the crystal characteristics of
      TAA in HFA propellant system, but had a significant impact on the crystal
      characteristics of BDP was higher than TAA at all propellant compositions,
      experimental temperatures and water levels investigated. The solubility of TAA
      and BDP was not only influenced by propellant composition and storage
      temperature, but also depended on the water level in the propellant system. As a
      consequence, the crystallinity of the drugs formulated in HFA propellant was
      influenced by the temperature, propellant composition and the water level in the
      propellant system. The impact of these factors on the crystallinity of formulated
      drugs.

PMID- 11247537
TI  - Activity profile of glycolamide ester prodrugs of ibuprofen.
AB  - Glycolamide esters of ibuprofen (I), namely, unsubstituted (II), N,N dimethyl
      (III), and N,N diethyl (IV), were synthesized and studied for different
      physicochemical, pharmacological, and toxicological properties. They were
      comparable with I in respect of anti-inflammatory and analgesic activity but did
      not exhibit reduction in the ulcerogenicity on oral administration. However, all
      three exhibited significantly better topical activity in carrageenan-induced rat
      paw edema assay. In the same assay, they provided significant protection against
      inflammation when applied at a site remote to the inflammation site.

PMID- 11247539
TI  - Study on tablet binding and disintegrating properties of alternative starches
      prepared from taro and sweet potato tubers.
AB  - To demonstrate the potential alternative sources of starch used in tablet
      formulations, starches from taro (TS) and sweet potato (SPS) tubers were prepared
      with obtained yields of 11.0 and 9.6%, respectively. Both TS and SPS met USP22
      NF17 identification and specifications. Their equilibrium moisture contents and
      gelatinization temperatures were comparable with those of commercial starch,
      whereas amylose contents of TS and SPS were 21.38% w/w and 41.76% w/w,
      respectively. Both were found to possess similar flow characteristics. To
      evaluate TS and SPS as granulating agents and disintegrants, tablets with
      controlled compression loads were prepared by incorporating a starch candidate
      with dibasic calcium phosphate in paste and powders forms, respectively. Tablets
      were then evaluated based on compressibility, friability, and disintegration. It
      was found that the binding and disintegrating performance of both TS and SPS was
      similar to that of commercial cornstarch.

PMID- 11247540
TI  - Development of a lyophilized formulation for (R,R)-formoterol (L)-tartrate.
AB  - (R,R)-formoterol is a beta-agonist for inhalation. Aqueous instability suggested
      the need for a reconstitutable lyophilized dosage form. The objective of these
      studies was to devise a stable, rapid-dissolving, therapeutically compatible
      dosage form. The effects of diluents and residual moisture on the stability of
      thermally stressed formoterol formulations were investigated. Drug and various
      excipients (acetate, lactose, and mannitol) were lyophilized and placed in
      humidity chambers (0 to 90% relative humidity) at 25 to 50 degrees C. Stability
      was characterized by time-dependent changes using HPLC, pH, and XRD. Residual
      moisture were determined by Karl Fisher methods. Regression models were developed
      to quantify the effects of formulation and environmental variation on drug
      stability. Solid-state instability was observed as a function of high residual
      moisture and diluent type. Although the residual moisture in mannitol
      formulations were typically below 1%, the degradation rate (50 degrees C) varied
      from 2 to 10 mcg/day, which was 1.3- to 20-fold high than observed for lactose
      formulations under the same relative humidity conditions. At high relative
      humidity, the presence of acetate significantly increased the degradation rate (p
      < 0.04). The critical residual moisture content for lactose formulations was 3%.
      The amount of lactose was optimized by evaluating the degradation over the
      temperature range 25 to 50 degrees C. Mannitol and acetate were shown to be
      unsuitable excipients, and an optimal lactose amount was 50 mg for vials
      containing 50 mcg of drug.

PMID- 11247542
TI  - Netting an important database.

PMID- 11247541
TI  - Synthesis and properties of dextran-linked ampicillin.
AB  - Ampicillin was coupled to dextran of average molecular weight 9,000 or 81,200 via
      the cyanogen bromide method. The degree of drug substituted per glucose unit
      (DSG) was varied from 0.104 to 0.028 (by weight bases: 22.1-5.9%) depending on
      the ratio of the reactants. Water solubility of dextran-linked ampicillin
      increased compared with free ampicillin, and the solubility decreased as the
      amount of ampicillin substituted increased. Plasma concentration of ampicillin,
      which appeared after intravenous administration of dextran-linked ampicillin in
      rats, was higher than when free ampicillin was administered, and the more so, the
      higher the molecular weight of dextran. Plasma half-life of dextran-linked
      ampicillin was two times longer than that of free ampicillin in rats.
      Antibacterial activities of dextran-linked ampicillin were evaluated against
      Staphylococcus aureus, Bacillus substillis, and Escherichia coli at two
      concentration levels according to the cup-plate method by measuring the diameter
      of inhibition zone, which was comparable to that of free ampicillin.

PMID- 11247543
TI  - Lung volume reduction surgery: a quality operation?

PMID- 11247544
TI  - CD36, insulin resistance, and coronary heart disease.

PMID- 11247546
TI  - Matrix metalloproteinases in pathophysiology and treatment of heart failure.

PMID- 11247545
TI  - Extending the role of allogeneic stem-cell transplantation.

PMID- 11247547
TI  - Insecticide resistance and mosquito-borne disease.

PMID- 11247548
TI  - Relation between plasma ascorbic acid and mortality in men and women in EPIC
      Norfolk prospective study: a prospective population study. European Prospective
      Investigation into Cancer and Nutrition.
AB  - BACKGROUND: Ascorbic acid (vitamin C) might be protective for several chronic
      diseases. However, findings from prospective studies that relate ascorbic acid to
      cardiovascular disease or cancer are not consistent. We aimed to assess the
      relation between plasma ascorbic acid and subsequent mortality due to all causes,
      cardiovascular disease, ischaemic heart disease, and cancer. METHODS: We
      prospectively examined for 4 years the relation between plasma ascorbic acid
      concentrations and mortality due to all causes, and to cardiovascular disease,
      ischaemic heart disease, and cancer in 19 496 men and women aged 45-79 years. We
      recruited individuals by post using age-sex registers of general practices.
      Participants completed a health and lifestyle questionnaire and were examined at
      a clinic visit. They were followed-up for causes of death for about 4 years.
      Individuals were divided into sex-specific quintiles of plasma ascorbic acid. We
      used the Cox proportional hazard model to determine the effect of ascorbic acid
      and other risk factors on mortality. FINDINGS: Plasma ascorbic acid concentration
      was inversely related to mortality from all-causes, and from cardiovascular
      disease, and ischaemic heart disease in men and women. Risk of mortality in the
      top ascorbic acid quintile was about half the risk in the lowest quintile
      (p<0.0001). The relation with mortality was continuous through the whole
      distribution of ascorbic acid concentrations. 20 micromol/L rise in plasma
      ascorbic acid concentration, equivalent to about 50 g per day increase in fruit
      and vegetable intake, was associated with about a 20% reduction in risk of all
      cause mortality (p<0.0001), independent of age, systolic blood pressure, blood
      cholesterol, cigarette smoking habit, diabetes, and supplement use. Ascorbic acid
      was inversely related to cancer mortality in men but not women. INTERPRETATION:
      Small increases in fruit and vegetable intake of about one serving daily has
      encouraging prospects for possible prevention of disease.

PMID- 11247549
TI  - Effectiveness of the direct observation component of DOTS for tuberculosis: a
      randomised controlled trial in Pakistan.
AB  - BACKGROUND: DOTS is the control strategy for tuberculosis promoted by WHO.
      Pakistan is currently developing its National Tuberculosis Programme, and
      requires guidance on types of direct observation of treatment appropriate for the
      local conditions. We did a randomised trial to assess the effectiveness of
      different packages for tuberculosis treatment under operational conditions in
      Pakistan. METHODS: We enrolled 497 adults with new sputum-positive tuberculosis.
      170 were assigned DOTS with direct observation of treatment by health workers;
      165 were assigned DOTS with direct observation of treatment by family members;
      and 162 were assigned self-administered treatment. The trial was done at three
      sites that provide tuberculosis services strengthened according to WHO guidelines
      for the purposes of the research, with a standard daily short-course drugs
      regimen (2 months of isoniazid, rifampicin, pyrazinamide, and ethambutol,
      followed by 6 months of isoniazid and ethambutol). The main outcome measures were
      cure, and cure or treatment completion. Analysis was by intention to treat.
      FINDINGS: Within the strengthened tuberculosis services, the health-worker DOTS,
      family-member DOTS, and self-administered treatment strategies gave very similar
      outcomes, with cure rates of 64%, 55%, and 62%, respectively, and cure or
      treatment-completed rates of 67%, 62%, and 65%, respectively. INTERPRETATION:
      None of the three strategies tested was shown to be superior to the others, and
      direct observation of treatment did not give any additional improvement in cure
      rates. The effectiveness of direct observation of treatment remains unclear, and
      further operational research is needed.

PMID- 11247550
TI  - Parents' accounts of obtaining a diagnosis of childhood cancer.
AB  - BACKGROUND: Quick diagnosis and treatment of cancers is a UK government priority.
      However, the process of arriving at a diagnosis of childhood cancer has been
      neglected in comparison with the attention given to cancers in adults. We
      investigated parents' narratives about the period before their child's diagnosis.
      METHODS: We undertook semistructured interviews with 20 parents whose children
      (aged 4-18 years) had a confirmed diagnosis of cancer or brain tumour. All
      interviews were recorded and fully transcribed. Dates of consultations and
      investigations were noted from children's medical records. Data were analysed by
      the constant comparison method. FINDINGS: The time before diagnosis is very
      significant for parents and might affect their adaptation and reaction to their
      child's diagnosis. Parents were first alerted to their child's illness by a range
      of signs and symptoms, and by behavioural and affective changes. These early
      symptoms were often vague, non-specific, and common, and some older children were
      reluctant to disclose symptoms. Ten families' accounts of this period before
      diagnosis included a dispute with doctors. Disagreements between parents and
      doctors about the seriousness of children's symptoms and the need for
      investigations occurred in both primary and secondary care. Some parents felt
      that doctors discounted their special knowledge of their child. INTERPRETATION:
      Parents' accounts offer valuable insights into their experiences of obtaining a
      diagnosis of childhood cancer and into possible sources of delays in this complex
      process. If delays are to be avoided or reduced, attention must be given to the
      different roles of parents, children, general practitioners, hospital
      specialists, and type of cancer. Our findings have important implications for
      policy, practice, and research, and for the management of childhood illnesses.

PMID- 11247551
TI  - Cell-wall-deficient bacteria and culture-negative febrile episodes in bone-marrow
      transplant recipients.
AB  - BACKGROUND: Although about 75-80% of neutropenic fevers are thought to be caused
      by infections, a causal organism can be confirmed microbiologically or suspected
      clinically in only 30-50%, and even fewer of these cases (16%) have a documented
      bacteraemia. The cause of neutropenic fever in the remaining cases remains
      elusive. We investigate the role of cell-wall-deficient bacteria in bone-marrow
      transplantation (BMT). METHODS: Blood cultures were obtained from bone-marrow
      transplant recipients and were inoculated into an aerobic bottle with resin, an
      anaerobic bottle, and a bottle to isolate cell-wall deficient bacteria. When
      growth was detected in the blood-culture bottle for cell-wall-deficient bacteria,
      20 microL of the broth was subcultured and the isolate identified by standard
      biochemical methods. The microbiological findings were correlated with the
      clinical characteristics of the patients. FINDINGS: From the 86 BMT recipients
      enrolled into the study, 798 sets of blood cultures were sent for laboratory
      analysis. 55 blood cultures were positive in the aerobic bottle, and the same
      isolates were also detected in 52 blood-culture bottles for cell-wall-deficient
      forms. For 20 sets of blood cultures, the isolates were detected only in the
      bottle for cell-wall-deficient forms. Blood for 13 (65%) of these 20 sets were
      sampled in the pre-engraftment neutropenic period, three (15%) during
      conditioning when the absolute neutrophil count was above 0.5 x 10(3)/L, and four
      (20%) in the post-engraftment period. 17 (85%) of the isolates were gram
      positive: four (20%) were Staphylococcus spp and ten (50%) were Bacillus spp.
      Antibiotic treatment was successful in 19 (95%) of 20 episodes. INTERPRETATION:
      Bacteraemia due to cell-wall-deficient forms causes a significant proportion of
      so-called culture-negative febrile episodes in BMT recipients.

PMID- 11247552
TI  - Survival estimates for patients with homozygous sickle-cell disease in Jamaica: a
      clinic-based population study.
AB  - BACKGROUND: Information about life expectancy of patients with homozygous sickle
      cell disease is needed for research and patient counselling. Our aim was to study
      two Jamaican populations, one clinic-based and one birth cohort and, by careful
      consideration of data quality and statistical analysis, to identify ways to
      increase the chances of obtaining valid and generalisable results. METHODS: We
      investigated the survival experience of 3301 patients with homozygous sickle-cell
      disease attending the Jamaican sickle-cell clinic between Jan 1, 1987, and Dec
      31, 1996. We applied and assessed a simulation technique for incorporating early
      life mortality using a birth cohort, and analysed the precision of this
      technique. Kaplan-Meier survival estimates are produced. FINDINGS: 290 of the
      3301 patients died. Median survival calculated with the excess mortality rate
      simulation data was 53 years (95% CI 49.3-57.0) for men and 58.5 (55.1-67.5) for
      women. INTERPRETATION: Our simulation technique, with realistic assumptions based
      on empirical evidence, offers a new estimate of median survival for patients with
      homozygous sickle-cell disease. We present the precision of these survival
      estimates, which introduces an important level of uncertainty. The inherent
      biases of clinically ascertained populations of patients, and the assumptions
      underlying analysis techniques are crucial features of survival studies in sickle
      cell disease, and can modify summary statistics substantially.

PMID- 11247553
TI  - Is it truly dementia?

PMID- 11247554
TI  - Dengue seroepidemiology in Singapore.
AB  - The resurgence of dengue in Singapore since 1986 had been associated with an
      adult predominance and a very low incidence in children. No study had been
      carried out to investigate this finding. Here we report a serological study of
      1068 children aged 0 to 15 years. There is a significant rise in seroconversion
      in children aged 6 years and older coinciding with the start of formal schooling.
      This suggests that there may be a change in the location where dengue is
      acquired.

PMID- 11247555
TI  - CD36 deficiency associated with insulin resistance.
AB  - No major genes responsible for insulin resistance have yet been identified. CD36
      is a multifunctional receptor, which plays a part in mediating intracellular
      signalling as well as in taking up biologically active substances such as long
      chain fatty acids. We looked for insulin resistance in genetic CD36 deficiency,
      which is common in Asian and African populations. The euglycaemic
      hyperinsulinaemic clamp technique showed insulin resistance in the five CD36
      deficient people tested. We conclude that CD36 could be responsible for insulin
      resistance.

PMID- 11247556
TI  - Prophylaxis with a nevirapine-containing triple regimen after exposure to HIV-1.
AB  - Evidence suggests that nevirapine, a non-nucleoside reverse-transcriptase
      inhibitor, might be very effective in the prevention of HIV-1 integration and the
      reduction of risk of HIV-1 acquisition after exposure. We used a triple
      combination regimen, including nevirapine, for prophylaxis after occupational or
      sexual exposure to HIV-1 infection. Of 57 individuals who started therapy, only
      41 returned for follow-up. Five had a grade three or four drug-induced hepatitis,
      two of whom also had a rash. This high rate of major adverse events raises
      concerns over the safety of such a regimen for its use in this population.

PMID- 11247557
TI  - Defective cellular trafficking of lacrimal gland aquaporin-5 in Sjogren's
      syndrome.
AB  - Dry eyes and dry mouth are clinical hallmarks of Sjogren's syndrome. We assessed
      the distribution of aquaporin-5 (AQP5) in lacrimal gland biopsy samples. Healthy
      controls and patients with Mikulicz's disease or non-Sjogren's syndrome dry eye
      had the expected apical distribution of AQP5 in lacrimal acinar cells. By
      contrast, cytoplasmic AQP5 was seen in patients with Sjogren's syndrome. Sodium
      channel and sodium-potassium ATPase distributions were normal in all groups.
      These findings show a selective defect in lacrimal gland AQP5 trafficking in
      Sjogren's syndrome that might contribute to decreased lacrimation and dry eye in
      these patients.

PMID- 11247558
TI  - Ischaemic colitis in a patient taking meloxicam.
AB  - The safety of cyclo-oxygenase 2 (COX-2) preferential inhibitors such as meloxicam
      is debated. We describe a patient who presented with bloody diarrhoea after 15 mg
      meloxicam daily for 10 days for osteoarthritis. The endoscopic and histological
      features were consistent with the diagnosis of ischaemic colitis. Symptoms and
      endoscopic lesions quickly regressed within 1 week of meloxicam withdrawal. There
      was no evidence of another cause of colonic ischaemia. We suggest that meloxicam
      might have intestinal toxic effects when taken in high doses, because of reduced
      COX-2 selectivity.

PMID- 11247559
TI  - US company's plan for trial in Latin America draws fire.

PMID- 11247560
TI  - What's the story H. pylori?

PMID- 11247561
TI  - Bulgaria's health-care reforms--there may be trouble ahead.

PMID- 11247562
TI  - Climate change likely to prove deadly, says United Nations report.

PMID- 11247563
TI  - Still a long way to go in the war against tobacco.

PMID- 11247564
TI  - Korea's pharmacists protest against drug law reforms.

PMID- 11247565
TI  - International leaders create billion-dollar fund to help world's poor children.

PMID- 11247566
TI  - Council of Europe proposes new approach to tackling drug abuse.

PMID- 11247567
TI  - Ireland discusses how to handle projected increase in medical litigation.

PMID- 11247568
TI  - Changing face of medical curricula.
AB  - The changing role of medicine in society and the growing expectations patients
      have of their doctors means that the content and delivery of medical curricula
      also have to change. The focus of health care has shifted from episodic care of
      individuals in hospitals to promotion of health in the community, and from
      paternalism and anecdotal care to negotiated management based on evidence of
      effectiveness and safety. Medical training is becoming more student centred, with
      an emphasis on active learning rather than on the passive acquisition of
      knowledge, and on the assessment of clinical competence rather than on the
      ability to retain and recall unrelated facts. Rigid educational programmes are
      giving way to more adaptable and flexible ones, in which student feedback and
      patient participation have increasingly important roles. The implementation of
      sustained innovation in medical education continues to present challenges,
      especially in terms of providing institutional and individual incentives.
      However, a continuously evolving, high quality medical education system is needed
      to assure the continued delivery of high quality medicine.

PMID- 11247569
TI  - The uses of error: missed opportunities.

PMID- 11247570
TI  - The Meuse Valley fog of 1930: an air pollution disaster.

PMID- 11247571
TI  - Misconceptions about the use of genetic tests in populations.

PMID- 11247573
TI  - The problems of medical relief agencies.

PMID- 11247572
TI  - Torture widespread in China.

PMID- 11247574
TI  - Emergencies in developed countries: are aid organisations ready to adapt?

PMID- 11247575
TI  - Blood-pressure-lowering treatment.

PMID- 11247576
TI  - Blood-pressure-lowering treatment.

PMID- 11247577
TI  - Blood-pressure-lowering treatment.

PMID- 11247578
TI  - Blood-pressure-lowering treatment.

PMID- 11247579
TI  - Blood-pressure-lowering treatment.

PMID- 11247580
TI  - Blood-pressure-lowering treatment.

PMID- 11247581
TI  - Blood-pressure-lowering treatment.

PMID- 11247582
TI  - Vitamin K for warfarin-associated coagulopathy.

PMID- 11247583
TI  - Drug therapy in paediatric patients.

PMID- 11247584
TI  - North Thames Dialysis Study.

PMID- 11247585
TI  - North Thames Dialysis Study.

PMID- 11247587
TI  - Ultrasonographic assessment of the scrotum.

PMID- 11247586
TI  - Antihypertensive drugs in Japan.

PMID- 11247588
TI  - Hypoplastic left-heart syndrome.

PMID- 11247589
TI  - Obstetricians' choice of delivery.

PMID- 11247590
TI  - Response to prednisolone in COPD.

PMID- 11247591
TI  - Where to practise evidence-based medicine?

PMID- 11247592
TI  - Where to practise evidence-based medicine?

PMID- 11247593
TI  - Where to practise evidence-based medicine?

PMID- 11247594
TI  - Treating the person.

PMID- 11247595
TI  - Spermatorrhoea.

PMID- 11247596
TI  - Religion, spirituality, and health care: social, ethical, and practical
      considerations.

PMID- 11247597
TI  - Late infections after blood progenitor cell transplantation in patients with
      multiple myeloma.

PMID- 11247598
TI  - Hypersensitivity syndrome associated with azithromycin.

PMID- 11247599
TI  - Mannitol-induced toxicity in a diabetic patient receiving losartan.

PMID- 11247600
TI  - Mesophyll-specific, light and metabolic regulation of the C4 PPCZm1 promoter in
      transgenic maize.
AB  - To play an essential role in C4 photosynthesis, the maize C4 phosphoenolpyruvate
      carboxylase gene (PPCZm1) acquired many new expression features, such as leaf
      specificity, mesophyll specificity, light inducibility and high activity, that
      distinguish the unique C4 PPC from numerous non-C4 PPC genes in maize. We present
      here the first investigation of the developmental, cell-specific, light and
      metabolic regulation of the homologous C4 PPCZm1 promoter in stable transgenic
      maize plants. We demonstrate that the 1.7 kb of the 5'-flanking region of the
      PPCZm1 gene is sufficient to direct the C4-specific expression patterns of beta
      glucuronidase (GUS) activity, as a reporter, in stable transformed maize plants.
      In light-grown shoots, GUS expression was strongest in all developing and mature
      mesophyll cells in the leaf, collar and sheath. GUS activity was also detected in
      mesophyll cells in the outer husks of ear shoots and in the outer glumes of
      staminate spikelets. We did not observe histological localization of GUS activity
      in light- or dark-grown callus, roots, silk, developing or mature kernels, the
      shoot apex, prop roots, or pollen. In addition, we used the stable expressing
      transformants to conduct and quantify physiological induction studies. Our
      results indicate that the expression of the C4 PPCZm1-GUS fusion gene is
      mesophyll-specific and influenced by development, light, glucose, acetate and
      chloroplast biogenesis in transgenic maize plants. These studies suggest that the
      adoption of DNA regulatory elements for C4-specific gene expression is a crucial
      step in C4 gene evolution.

PMID- 11247601
TI  - Protein phosphatase 2A: identification in Oryza sativa of the gene encoding the
      regulatory A subunit.
AB  - A 2225 bp cDNA, designated RPA1, was isolated from an Oryza sativa cDNA library.
      Analysis revealed a 1761 bp coding sequence with 15 non-identical repeat units.
      The ORF encoded the A regulatory subunit of protein phosphatase 2A (PP2A-A) as
      ascertained by complementation of the yeast tpd3 mutant defective in this gene.
      The corresponding genomic DNA from a rice genome BAC library revealed that the
      gene contains eleven introns. The rice genome contains only a single copy of this
      gene as judged by Southern blot analysis. The PP2A protein is highly conserved in
      nature; the rice protein shows 88% amino acid identity with its counterparts in
      Arabidopsis or Nicotiana tabacum.

PMID- 11247602
TI  - High-resolution mapping of YACs and the single-copy gene Hs1(pro-1) on Beta
      vulgaris chromosomes by multi-colour fluorescence in situ hybridization.
AB  - Fluorescence in situ hybridization (FISH) is a powerful approach for physical
      mapping of DNA sequences along plant chromosomes. Nematode-resistant sugar beets
      (Beta vulgaris) carrying a Beta procumbens translocation were investigated by
      FISH with two differentially labelled YACs originating from the translocation. At
      mitotic metaphases, the translocation was identified with both YACs in the
      terminal region on a pair of chromosomes. Meiotic chromosomes, representing a far
      more extended hybridization target, were used to determine the orientation of
      YACs with respect to chromosomal domains in combination with chromosomal landmark
      probes for telomeres and centromeres. The in situ detection of plant single-copy
      sequences is technically difficult, and the wild beet translocation was used to
      explore the potential resolution of the FISH approach and to introduce the
      chromosomal mapping of single-copy genes into genome analysis of Beta species. An
      internal fragment of the nematode resistance gene Hs1(pro-1), 684 bp long, was
      detected on both chromatids of different Beta chromosomes and represents one of
      the shortest unique DNA sequences localized on mitotic plant chromosomes so far.
      Comparative chromosomal mapping of the 684 bp Hs1(pro-1) probe in the
      translocation line, a monosomic addition line and in B. procumbens revealed the
      origin of the wild beet translocation leading to nematode-resistant sugar beets.

PMID- 11247603
TI  - Tissue-dependent enhancement of transgene expression by introns of replacement
      histone H3 genes of Arabidopsis.
AB  - Intron-bearing replacement histone H3 genes in Arabidopsis and other plants are
      highly and constitutively expressed. We demonstrate that the introns located
      within the 5'-untranslated regions (5'-UTR) of the two Arabidopsis replacement H3
      genes will abolish the cell cycle dependence of an endogenous histone H4
      promoter. We demonstrate that these introns, functionally combined with their
      endogenous promoters, could produce the high and constitutive expression of the
      replacement H3 genes observed in planta. They strongly increase gene expression
      whatever the promoter, from the strong 35S CaMV promoter to complete and resected
      promoters of cell cycle-dependent and replacement histone genes. Quantitative
      analysis of the extent of reporter gene enhancement in different parts of
      developing transgenic plantlets, ranging from 2-fold to 70-fold, supports the
      notion that trans-acting factors are responsible for this effect. Such factors
      appear most abundant in roots.

PMID- 11247604
TI  - Surveying CpG methylation at 5'-CCGG in the genomes of rice cultivars.
AB  - We investigated the CpG methylation status of the sequence CCGG in the rice
      genome by using methylation-sensitive AFLP and subsequent Southern analyses with
      the isolated AFLP fragments as probes. CpGs located in single- or low-copy
      sequence regions could be grouped into two classes on the basis of their
      methylation status: methylation status at the class 1 CpG sites was conserved
      among genetically diverse rice cultivars, whereas cultivar-specific differential
      methylation was frequently detected among the cultivars at the class 2 CpG sites.
      The frequency of occurrence of methylation polymorphism between a pair of
      cultivars was not related to the genetic distance between the two. Through
      mapping, five class 2 CpG sites were localized on different chromosomes and were
      not clustered together in the genome. Segregation analysis of the cultivar
      specific methylations with their target sites indicated that the differential
      methylation was stably inherited in a Mendelian fashion over 6 generations,
      although alterations in the methylation status at the class 2 CpG sites were
      observed with a low frequency.

PMID- 11247605
TI  - A recombinase-mediated transcriptional induction system in transgenic plants.
AB  - We constructed and tested a Cre-loxP recombination-mediated vector system termed
      pCrox for use in transgenic plants. In this system, treatment of Arabidopsis
      under inducing conditions mediates an excision event that removes an intervening
      piece of DNA between a promoter and the gene to be expressed. The system
      developed here uses a heat-shock-inducible Cre to excise a DNA fragment flanked
      by lox sites, thereby generating a constitutive GUS reporter gene under control
      of the CaMV 35S promoter. Heat-shock-mediated excision of several, independent
      lines resulted in varying degrees of recombination-mediated GUS activation.
      Induction was shown to be possible at essentially any stage of plant growth. This
      single vector system circumvents the need for genetic crosses required by other,
      dual recombinase vector systems. The pCrox system may prove particularly useful
      in instances where transgene over-expression, or under-expression by antisense,
      would otherwise affect embryo, seed or seedling viability.

PMID- 11247606
TI  - The brassica MIP-MOD gene encodes a functional water channel that is expressed in
      the stigma epidermis.
AB  - In crucifers, the ability of the stigma to differentially modulate hydration of
      pollen grains, depending on whether the pollen is recognized to be compatible or
      incompatible, represents a crucial stage in pollination. Our recent analysis of
      the mod mutation of Brassica, which results in a breakdown of the self
      incompatibility response, led to the isolation of a gene linked to the MOD locus
      which is expressed at low levels in mod mutants. The gene is predicted to encode
      a plasma membrane-localized aquaporin-like protein and has been designated MIP
      MOD. We utilized reporter gene analysis to demonstrate that the MIP-MOD promoter
      is active in Brassica papillar cells as well as in some vegetative tissues. The
      encoded protein is also likely to be plasma membrane-localized based on the
      observation that all plasma membrane-intrinsic aquaporin-like proteins in
      Brassica leaves are enriched in plasma membrane fractions. The MIP-MOD protein
      results in a low but measurable enhancement in osmotic water permeability of
      Xenopus oocytes and hence represents a functional aquaporin. The results are
      consistent with the notion that MIP-MOD is involved in the regulation of water
      transport across the stigma epidermal cell membrane.

PMID- 11247607
TI  - DNA-binding and dimerization preferences of Arabidopsis homeodomain-leucine
      zipper transcription factors in vitro.
AB  - Homeodomain-leucine zipper (HDZip) proteins constitute a large family of
      transcription factors apparently unique to plants. In this report we characterize
      the DNA-binding and dimerization preferences in vitro of class I HDZip proteins.
      Using gel-exclusion chromatography and in vitro protein binding assays we
      demonstrate that the HDZip class I protein ATHB5 forms a homodimeric complex in
      solution. Consistent with this finding we have demonstrated the sequence-specific
      interaction of ATHB5 with a 9 bp pseudopalindromic DNA sequence, CAATNATTG,
      composed of two half-sites overlapping at a central position, by use of a PCR
      assisted binding-site selection assay and competitive EMSA experiments. A
      majority of other known members of HDZip class I interacted with similar DNA
      sequences, but differed in their preference for A/T versus G/C in the central
      position of the binding site. Selective heterodimerization in vitro was
      demonstrated between ATHB5 and different class I HDZip proteins. Heterodimer
      formation between class I HDZip proteins is of potential functional significance
      for the integration of information from different signalling pathways in the
      control of plant development.

PMID- 11247610
TI  - Gestational diabetes: universal or selective screening?

PMID- 11247608
TI  - Molecular cloning and expression in yeast of 2,3-oxidosqualene-triterpenoid
      cyclases from Arabidopsis thaliana.
AB  - A vast array of triterpenes are found in living organisms in addition to
      lanosterol and cycloartenol, which are involved in sterol biosynthesis in non
      photosynthetic and photosynthetic eukaryotes respectively. The chemical structure
      of these triterpenes is determined by a single step catalysed by 2,3
      oxidosqualene-triterpene cyclases. The present study describes cloning and
      functional expression in yeast of several OS-triterpene cyclases. Three
      Arabidopsis thaliana cDNAs encoding proteins (ATLUP1, ATLUP2, ATPEN1) 57%, 58%
      and 49% identical to cycloartenol synthase from the same plant were isolated.
      Expression of these cDNAs in yeast showed that the recombinant proteins catalyse
      the synthesis of various pentacyclic triterpenes. Whereas ATLUP1 is essentially
      involved in the synthesis of lupeol, ATLUP2 catalyses the production of lupeol,
      beta- and alpha-amyrin (in a 15:55:30 ratio). ATLUP2 is therefore a typical
      multifunctional enzyme. Under the same conditions, ATPEN1 did not lead to any
      product. Systematic sequencing of the Arabidopsis genome has led to genomic
      sequences encoding proteins identical to the above triterpene synthases. ATLUPI
      and ATLUP2 are representative of a small subfamily (A) of at least five genes,
      whereas ATPEN1 is representative of a subfamily (B) of at least seven genes. The
      number of introns is characteristic of each subfamily. Whereas genes of family A
      possess 17 exons and 16 introns, genes of the subfamily B contain 14 exons and 13
      introns. The size of each exon is remarkably conserved within each subfamily
      whereas that of each intron appears to be highly variable. Organization of the
      genes, sequences and functions of the deduced proteins are discussed in
      evolutionary terms.

PMID- 11247611
TI  - Bed availability and transfer of critically ill patients.

PMID- 11247609
TI  - Expression of a membrane-anchored endo-1,4-beta-glucanase from Brassica napus,
      orthologous to KOR from Arabidopsis thaliana, is inversely correlated to
      elongation in light-grown plants.
AB  - A PCR fragment derived from a membrane-anchored endo-1,4-beta-glucanase cDNA was
      amplified using degenerated oligonucleotides and mRNA from oilseed rape (Brassica
      napus L.) siliques. Sequence analysis of the corresponding gene, Cel16, showed
      that the predicted Cel16 protein has high identity with the Arabidopsis KOR
      protein (94%). High-stringency genomic Southern analysis further revealed that
      Cel16 and KOR are most likely orthologous genes performing a similar function in
      both species. Northern blot and GUS analysis of transgenic Arabidopsis containing
      a fusion between a 2.0 kb Cel16 promoter fragment and the GUS reporter gene
      showed that Cel16 was expressed at a low level in the primary raceme, the young
      lateral stems, the elongation zone of the primary root and the older root base.
      By contrast, a high level of Cel16 mRNA accumulation was found in the young root
      and in the main stem carrying flowers and young siliques. Cel16 transcripts were
      localized to the apical meristem, cambium, primary xylem and cortex of oilseed
      rape stem tissue by in situ RT-PCR. A similar pattern of activity was found in
      the GUS analysis of transgenic Arabidopsis. Cel16 mRNA accumulation in the main
      stem was lower in the zone of most rapid cell elongation than in the subjacent,
      fully elongated internodes. Similarly, Cel16 transcripts accumulated to a higher
      level in leaves as they reached full size than during early leaf expansion.
      Analysis of the expression pattern in elongating, light-grown seedlings showed
      that Cel16 mRNA accumulated at a lower level in the elongating upper third than
      elsewhere in the hypocotyl. This is contrary to etiolated hypocotyls, where we
      found a higher expression level in the rapidly elongating upper part. This
      difference in expression most probably reflects a difference in cell wall
      assembly between light- and dark-grown seedlings.

PMID- 11247612
TI  - Male infertility: the case for continued research.

PMID- 11247613
TI  - Selective versus universal screening for gestational diabetes mellitus: an
      evaluation of predictive risk factors.
AB  - OBJECTIVE: To assess whether selective screening for gestational diabetes
      mellitus (GDM) on the basis of risk-factor assessment is a practicable
      alternative to universal screening. DESIGN: Case-control study. SETTING: A 212
      bed regional specialist hospital in Melbourne, providing services in obstetrics
      and gynaecology, paediatrics, geriatrics and rehabilitation. SUBJECTS: 6,032
      women who gave birth at the hospital, May 1996 to August 1997 and November 1997
      to August 1998; all were screened for GDM, and 313 were diagnosed with the
      condition. MAIN OUTCOME MEASURES: Odds ratios (ORs) for risk factors (age,
      obesity, family history of diabetes mellitus and high-risk racial heritage) in
      women with GDM compared to those without GDM; proportion of women with GDM whose
      diagnosis would have been missed by selective screening. RESULTS: ORs were 1.9
      for age > or = 25 years (95% CI, 1.3-2.7), 2.3 for body mass index > or = 27kg/m2
      (95% CI, 1.6-3.3), 2.5 for high-risk racial heritage (95% CI, 2.0-3.2), and 7.1
      for family history of diabetes mellitus (95% CI, 5.6-8.9). Other proposed
      criteria (previous GDM and glycosuria) added no further diagnostic power.
      Selective screening using the above four criteria would have missed two of 313
      cases (0.6%) and could have saved screening up to 1,025 women without GDM (17% of
      all women). CONCLUSIONS: Selective screening for GDM based on prior risk
      assessment can reduce the need for testing, with negligible loss of diagnostic
      efficiency.

PMID- 11247614
TI  - Outcome of critically ill patients undergoing interhospital transfer.
AB  - OBJECTIVE: To quantify the morbidity and mortality associated with acute
      interhospital transfer of critically ill patients requiring intensive care (ICU)
      services. DESIGN: Three-year (1 July 1996-30 June 1999) retrospective case
      control study based on review of patients' medical records. SETTING: Metropolitan
      hospitals in Melbourne, Victoria. PARTICIPANTS: 73 (of 75) consecutive,
      critically ill patients from one metropolitan teaching hospital who were
      transferred to other hospitals because ICU services were not available. OUTCOME
      MEASURES: Primary endpoints included inhospital mortality and length of stay in
      ICU and hospital. Secondary endpoints included time from study entry to ICU
      admission and the change in predicted mortality risk after resuscitation and
      transfer to ICU (inter- or intrahospital transfer). RESULTS: The Transfer Group
      experienced a significant delay in admission to ICU (5.0 [4.0-6.0] v 3.0 [2.0
      5.5] hours; P=0.001), and a longer stay in ICU (48 [33-111] v 44 [25-78] hours;
      P=0.04), and hospital (10 [3-14] v 6 [3-13] days; P=0.02). Hospital mortality in
      the Transfer Group (24.7%) was not statistically different from that in the
      Control Group (17.8%; P= 0.41; OR, 1.5; 95% CI, 0.68-3.4). CONCLUSION: Acute
      interhospital transfer is associated with a delay in ICU admission and a longer
      stay in ICU and hospital, but no statistically significant difference in
      mortality. A study of over 300 patient transfers would be required to clarify the
      morbidity and mortality risk of acute interhospital transfer.

PMID- 11247615
TI  - Management of women with minor abnormalities of the cervix detected on screening:
      a qualitative study.
AB  - OBJECTIVE: To examine the consistency of decisions by pathology staff and general
      practitioners in managing women in whom minor cervical abnormalities are detected
      by screening, with current National Health and Medical Research (NHMRC) Council
      guidelines, and to look at reasons for inconsistencies. DESIGN: Qualitative
      interview study. PARTICIPANTS: 14 pathology staff (12 pathologists and two
      cytoscientists) from 10 of the 17 laboratories providing cervical cytology
      services in Victoria, and a sample of 22 GPs from metropolitan and rural
      locations in Victoria. MAIN OUTCOME MEASURES: Comparison of management practice
      with NHMRC guidelines; reasons for current decision-making practice. RESULTS:
      Most pathologists provided more cautious recommendations for minor abnormalities
      of the cervix than the NHMRC recommendations in all reporting categories except
      human papillomavirus. Pathologists had concerns about the appropriateness of the
      NHMRC recommendations, particularly for glandular atypia, lack of an endocervical
      component and inflammatory smears, where they believed that the NHMRC
      recommendations were not well supported by evidence. GPs generally followed the
      recommendations of their laboratories. Medicolegal concerns were a major
      influence on clinical decisions for both pathologists and GPs, and have
      contributed to the development of cautious management practice. Reporting and
      management practice of pathologists and GPs reflects the ambiguity of minor
      cervical abnormalities that the NHMRC guidelines fail to highlight. CONCLUSION:
      Many pathologists and GPs are reluctant to follow NHMRC guidelines because they
      believe they are inadequate for some minor cervical abnormalities. The cervical
      screening guidelines should be reviewed according to the NHMRC guidelines for
      developing clinical practice guidelines, to promote consistent practice based on
      an up-to-date, accurate evidence base.

PMID- 11247616
TI  - What are appropriate rates of invasive procedures following acute myocardial
      infarction? A systematic review.
AB  - OBJECTIVE: To assess the evidence that higher rates of coronary angiography (CA)
      and revascularisation (RV) in the subacute phase of acute myocardial infarction
      (AMI) improve patient outcomes. DATA SOURCES: MEDLINE 1990 - December 1999,
      Current Contents 1990-1999, Cochrane Library (Issue 4, 1999), HealthSTAR 1990
      1999, selected websites and bibliographies of retrieved articles. STUDY SELECTION
      AND DATA EXTRACTION: Studies selected were (1) randomised trials comparing
      outcomes of "invasive" versus "conservative" use of CA and RV following AMI; (2)
      observational studies with formal methods comparing outcomes of high versus low
      rates of use of these procedures; and (3) clinical practice guidelines (CPGs),
      expert panel statements and decision analyses which met critical appraisal
      criteria, and which specified procedural indications. Outcome measures were rates
      of mortality, re-infarction and limiting or unstable angina. DATA SYNTHESIS: 56
      articles were identified; 24 met inclusion criteria. Pooled data from nine RCTs
      of "invasive" (CA rate 96%; RV rate 66%) versus "conservative" (CA rate 28%; RV
      rate 19%) strategies showed no significant differences in mortality or re
      infarction rates. Pooled results from 12 observational studies showed no
      mortality differences, but an excess reinfarction rate (8.0% vs 6.4%; P<0.001) in
      high- versus low-rate populations. Evidence of survival benefit from procedural
      intervention was strongest for patients with recurrent ischaemia combined with
      left ventricular dysfunction. CONCLUSIONS: In the subacute phase of AMI, rates of
      CA and RV in excess of 30% and 20%, respectively, may not confer additional
      benefit in preventing death or re-infarction. However, variability between
      studies in design, patient selection, and extent of cross-over from medical to
      procedural groups, as well as limited data on symptom status, limits
      generalisability of results.

PMID- 11247617
TI  - Idiopathic pulmonary fibrosis: in need of focused and systematic management.
AB  - Idiopathic pulmonary fibrosis (IPF) is an increasingly recognised, serious lung
      disease. A recent International Consensus Statement has redefined the term
      "idiopathic pulmonary fibrosis", restricting its use to the entity previously
      described as "usual interstitial pneumonia" and reclassifying some of the more
      benign inerstitial lung diseases formerly included under IPF. There is
      insufficient quality evidence for the effectiveness of current medical therapies
      for IPF. Lung transplantation provides a potential surgical therapeutic option
      for selected individuals with IPF, but referral for transplant needs to be made
      as early as possible. Multidisciplinary clinics specialising in interstitial lung
      disease have a potential role in determining which patients may benefit from
      novel and existing medical therapies and which patients should be referred for
      lung transplantation.

PMID- 11247618
TI  - What is the optimal treatment for hypothyroidism?
AB  - Standard treatment of primary hypothyroidism is with thyroxine, with the aim of
      relieving symptoms and bringing the serum TSH (thyroid-stimulating hormone)
      concentration to within the reference range. Recent research suggests that in
      some patients symptoms of hypothyroidism persist despite standard thyroxine
      replacement therapy. The optimal treatment of these patients is not known.
      Adjusting the thyroxine dose until the serum TSH concentration is in the lower
      part of the reference range (eg, 0.3-2.0 mU/L) may be beneficial. Animal studies
      and a single small clinical trial suggest that a combination of thyroxine and T3
      (triiodothyronine), rather than thyroxine alone, may be required for optimal
      thyroid replacement therapy. Further research is needed to determine why some
      patients appear to have a suboptimal response to thyroxine, and whether combined
      thyroxine/T3 treatment is preferable to thyroxine alone in these patients.

PMID- 11247620
TI  - What is the best emergency treatment for children who ingest warfarin
      rodenticide?

PMID- 11247619
TI  - Do doctors know best? Comments on a failed trial.
AB  - A randomised controlled trial was planned to compare two different treatment
      strategies--structured problem solving and selective serotonin reuptake inhibitor
      (SSRI) medication--for patients with mild to moderate major depression. The trial
      was to be conducted in the primary care setting with all treatment given by
      general practitioners. When no patients had been recruited into the study after
      six months, we performed an audit of all patients with depressive symptoms
      attending the doctors' practices over three weeks. Exclusion criteria were
      changed to ease entry into the trial, but still no patients were recruited over
      the following six months. What went wrong?

PMID- 11247621
TI  - Health and safety information carried by travel brochures in Australia.

PMID- 11247622
TI  - Vitamin D insufficiency in south-east Queensland.

PMID- 11247623
TI  - Munchausen's syndrome.

PMID- 11247624
TI  - Use of the Autopap as a primary automated cervical cancer screening system.

PMID- 11247625
TI  - The autopsy in private hospitals in Victoria.

PMID- 11247626
TI  - Predictive value of personal recall of chicken pox infection: implications for
      the use of varicella vaccine.

PMID- 11247627
TI  - Nitrofurantoin and peripheral neuropathy: a forgotten problem?

PMID- 11247628
TI  - Career choices of Junior Medical Officers: influence of a general practice term.

PMID- 11247630
TI  - Imagined ugliness: a symptom which can become a disorder.

PMID- 11247629
TI  - Anorexia nervosa, infertility and pregnancy.

PMID- 11247631
TI  - The drosophila genome and its oncological implications.
AB  - The genome of the fruit fly has recently been sequenced, prior to the release of
      the human genome sequence within the next few years. The fly has some 13 600
      genes, compared with the estimated 80 000 genes in the human genome. Some 70% of
      genes appear to be broadly conserved across eukaryotic species, and some
      remarkable homologies have been found between 177 genes in the fly and the 289
      human genes so far associated with diseases in man. The fruit fly genome is
      likely to prove an elegant model and a rich source of experimentation for the
      aetiology and regulation of human cancers.

PMID- 11247633
TI  - Color Doppler sonographic findings of fetal upper respiratory tract obstruction.

PMID- 11247632
TI  - Soft tissue carcinoma in the retroperitoneum: an often neglected diagnosis.
AB  - AIMS: Successful surgical treatment of patients with retroperitoneal soft tissue
      sarcoma (RSTS) is based on pre-operative planning that starts with a correct pre
      operative diagnosis. In a population-based study, we determined which patients
      were initially treated for assumed other conditions. The effect of an erroneous
      diagnosis on the installed treatment was analysed. METHOD: With the help of the
      Dutch Network and National Database for Pathology (PALGA), data were collected on
      143 patients in the Netherlands in whom a primary RSTS was found and confirmed
      histologically between 1 January 1989 and 1 January 1994. Satisfactory clinical
      information was obtained on 138 patients, 64 males and 74 females (54%). The
      median age was 60 (range 18-88) years. RESULTS: At the time of actual treatment
      37% of the patients with RSTS were assumed to have another disorder (group 1
      n=51), whereas 87 patients were diagnosed as having RSTS (group 2). In group 1,
      an acute presentation was more common (18 vs 2% P=0.002), and the tumour was less
      often palpable at physical examination (43 vs 69% P=0.004), while clinical work
      up less frequently included CT-imaging (57 vs 89% P<0.001) and a biopsy (29 vs
      77% P<0.001). Although tumours in group 1 were smaller (median diameter 13 vs 19
      cm P<0.05), this was not reflected in a better operative result: less patients
      underwent complete tumour resection (51 vs 57%) and more patients underwent
      surgery for tumours that proved to be irresectable (14 vs 1% P=0.004).
      CONCLUSIONS: (1) More than one-third of patients with RSTS are misdiagnosed and
      inappropriately treated; and (2) biopsies and cross-sectional imaging improve
      diagnosis.

PMID- 11247634
TI  - IL-12 enhances lymphoaccumulation by suppressing cell death of T cells in MRL-
      lpr/lpr mice.
AB  - Lymphoaccumulation occurs in MRL- lpr/lpr mice, because double-negative T cells
      (DNT cells) cannot be deleted due to their Fas mutation, i.e., lpr. We show here
      that IL-12 enhances in lymphoaccumulation by suppressing cell death of DNT cells
      in [corrected] MRL- lpr/lpr mice. It has been reported that viable DNT cells from
      MRL- lpr/lpr mice undergo rapid apoptosis in ordinary cell culture without
      additional stimulation, suggesting that unknown in vivo factors other than lpr
      suppress the apoptosis. In the present study, we found that plasma IL-12p40
      monomer and/or homodimer level increased with age in MRL- lpr/lpr but not in MRL
      +/+ mice, and the increase in IL-12 correlated well with lymphoaccumulation.
      Requirement of IL-12 in lymphoaccumulation and in suppressed cell death of DNT
      cells of MRL- lpr/lpr mice was assessed. When an antibody neutralizing IL-12 was
      injected into old MRL- lpr/lpr mice with high plasma IL-12 level,
      lymphoaccumulation was diminished. When IL-12p40- or IL-12p70-encoding plasmid
      was administered to young MRL- lpr/lpr mice before the plasma IL-12 level
      increases, lymphoaccumulation was enhanced. The ordinary cell culture-induced
      cell death of DNT cells from MRL- lpr/lpr mice was suppressed in the presence of
      IL-12. Since DNT cells produce IFN-gamma, a potent inducer of IL-12, the INF
      gamma induced-IL-12 may enhance lymphoaccumulation in MRL- lpr/lpr mice.

PMID- 11247635
TI  - IL-12 plays a pathologic role at the inflammatory loci in the development of
      diabetes in NOD mice.
AB  - Accumulating evidence suggests that CD4(+)T helper type 1 (Th1) cells play a
      major role in the development of insulin-dependent diabetes mellitus (IDDM) in
      the non-obese diabetic (NOD) mouse model. Interleukin (IL)-12 is a potent
      immunoregulatory molecule that is a key determinant of T-cell differentiation
      into Th1 cells, and has been implicated in the development of IDDM. To
      investigate the role of IL-12 that is locally produced by islet-infiltrating
      cells in the development of IDDM, we generated transgenic NOD mice in which the
      IL-12 p40 homodimer, a natural antagonist of IL-12, was produced exclusively in
      islets without affecting the levels of IL-12 p40 in the systemic circulation. We
      found that the incidence of diabetes was significantly reduced in these
      transgenic mice. These results clearly demonstrate that IL-12 locally produced by
      islet-infiltrating cells plays a critical role in the development of IDDM.

PMID- 11247636
TI  - CTLA-4-/- mice display T cell-apoptosis resistance resembling that ascribed to
      autoimmune-prone non-obese diabetic (NOD) mice.
AB  - The genes conferring susceptibility to autoimmune (insulin-dependent) diabetes
      mellitus (IDDM) are, in most cases, not defined. Among the loci so far identified
      as associated with murine IDDM (Idd1-19), only the nature of Idd1 has been
      assessed. Here we show that thymocytes and peripheral lymphocytes of the non
      obese diabetic (NOD) mouse are relatively resistant to apoptosis induced by gamma
      irradiation. By linkage analysis of F2 progeny mice, we map this trait to a locus
      on chromosome 1 containing the Idd5 diabetes susceptibility region. By the use of
      congenic mice, we confirm the linkage data and map this locus to a 6 cM region on
      proximal chromosome 1. Ctla4, being localized in this chromosomal region and
      mediating crucial functions in T cell biology, is a logical candidate gene in the
      Idd5 susceptibility region. In line with this, we demonstrate that T cells from
      Ctla4(-/-)deficient mice show a similar resistance to gamma-irradiation-induced
      apoptosis as observed in the NOD mice. This reinforces the notion that CTLA-4
      contributes to the pathogenesis of autoimmune diabetes.

PMID- 11247638
TI  - Toxic shock syndrome toxin-1 accelerated collagen-induced arthritis in mice.
AB  - The aim of this study was to explore the roles of toxic shock syndrome toxin-1
      (TSST-1) in collagen-induced arthritis (CIA). DBA/1 mice were immunized with type
      II collagen (CII) and treated with TSST-1. Intraperitoneal and intravenous
      injections of TSST-1 aggravated CIA, enhancing its incidence and severity. CIA
      was accompanied by an increase in anti-CII IgG Ab levels. Intraperitoneal
      administration with TSST-1 enhanced IFN-gamma, TNF-alpha, and IL-4 production in
      DBA/1 mice. We discovered the mRNA expressions of IFN-gamma, IL-2, TNF-alpha, IL
      1beta, and iNOS in spleen cells stimulated with TSST-1 in vitro. However, IL-12
      and IL-4 mRNA expression were seen constitutively without stimulation. Only a
      little increase of IL-12 and IL-4 mRNA expression was seen at 2-3 h after
      treatment with TSST-1. Our experiments demonstrated that CIA was aggravated by
      the treatment with TSST-1, which may have induced various proinflammatory
      cytokines and the production of both Th1 and Th2 cytokines.

PMID- 11247637
TI  - Differential cytokine requirements for regulation of autoimmune gastritis and
      colitis by CD4(+)CD25(+) T cells.
AB  - Murine autoimmune gastritis, induced by neonatal thymectomy or the injection of
      CD25-depleted lymphocytes into nu/nu recipients, is characterized by an
      inflammatory infiltrate into the gastric mucosa, parietal cell destruction and
      circulating anti-parietal cell antibodies. Using RAG-2(-/-)mice as recipients, we
      determined that the induction of disease relies on CD4(+)CD25(-)effector cells
      and prevention relies on CD4(+)CD25(+)regulatory cells; neither requires
      participation of CD8 cells or B cells. The severity of gastritis was dependent on
      the cytokine repertoire of CD4(+)CD25(-)effector T cells. Recipients of IL-4(-/
      )T cells developed more severe gastritis and recipients of INF-gamma(-/-)T cells
      developed milder disease than recipients of wildtype or IL-10(-/-)effector T
      cells. Gastritis did not develop in the absence of IL-12. Protection from
      gastritis does not require either IL-4 or IL-10 because CD4(+)CD25(+)cells from
      IL-4(-/-)or IL-10(-/-)mice completely abrogated the disease process.
      CD4(+)CD25(+)cells also protected RAG-2(-/-)recipients from colitis and
      inhibitory activity was partially dependent on IL-10 expression. These findings
      highlight the critical role of CD4(+)CD25(+)regulatory T cells in protection from
      several autoimmune syndromes and delineate the differential contribution of IL-10
      to CD4(+)CD25(+)Treg activity in the settings of gastritis and colitis.

PMID- 11247640
TI  - Autoantibodies against neonatal heart M1 muscarinic acetylcholine receptor in
      children with congenital heart block.
AB  - Isolated congenital heart block may be associated with autoimmune disorder such
      as Sjogren Syndrome and systemic lupus erythematosus. In this work we demonstrate
      circulating autoantibodies against neonatal heart M1 muscarinic acetylcholine
      receptor (mAChR) in the sera of children with congenital heart block. This
      antibody were able to react with the second extracellular loop of the human M1
      mAChR as demonstrated using a synthetic peptide in enzyme immune assay and
      binding assay. Affinity purified anti-peptide IgG as well as total IgG from
      children with congenital heart block, interfered with the specific radioligand
      occupancy from neonatal heart M1 mAChR, interacting irreversibly. The antipeptide
      antibodies also displayed an 'agonist-like' activity, i.e. decreased
      contractility, activated nitric oxide synthase activity and increased production
      of cyclic GMP. All of these effects were selectively blunted by pirenzepine and
      neutralized by the synthetic M1 peptide. Both binding and biological effects were
      obtained using neonatal rat heart instead adult heart and were independent of
      Ro/SS-A and La/SS-B antibodies and were also absent in the sera of normal
      children. A clinical relevance of these findings is demonstrated by a strong
      association between the existence of circulating M1 mAChR antipeptide antibodies
      and the presence of isolated congenital heart block, making these antibodies a
      proper marker of this disease.

PMID- 11247639
TI  - Polymorphisms/mutations of TCR-zeta-chain promoter and 3' untranslated region and
      selective expression of TCR zeta-chain with an alternatively spliced 3'
      untranslated region in patients with systemic lupus erythematosus.
AB  - A vast majority of systemic lupus erythematosus (SLE) patients display decreased
      expression of TCR zeta-chain mRNA, a critical signaling molecule implicated in
      the selection of the TCR repertoire and in the prevention of autoimmunity. To
      identify the molecular mechanisms involved in the downregulation of TCR zeta
      chain transcripts in SLE T cells, we investigated the possibility of
      polymorphisms/mutations in the promoter and the 3' untranslated region. PCR,
      cloning and sequence analysis of the promoter region from the genomic DNA showed
      significantly higher number of polymorphisms in SLE T cells compared to non-SLE
      control subjects (P = 0.044). Promoter sequence was also analysed from
      granulocytes to delineate the possibility of somatic mutations in activated SLE T
      cells. Promoter polymorphisms were significantly higher in granulocytes of SLE
      patients compared to non-SLE controls (P = 0.048), suggesting that these
      polymorphisms were of genomic origin. Nucleotide analysis of the promoter
      sequence revealed a -76T insertion compared to the published sequence, in all of
      the SLE samples and controls. RT-PCR analysis of the TCR zeta-chain 3'
      untranslated region showed a 344 bp product in addition to the expected 906 bp
      product. Cloning and sequence analysis of the 344 bp product indicated that it is
      an alternatively spliced form with both splicing donor and acceptor sites,
      resulting in deletion of nucleotides 672-1233 of TCR zeta-chain mRNA. Unlike the
      nomal TCR zeta-chain, the expression of TCR zeta-chain with the alternatively
      spliced 344 bp 3' untranslated region was higher in SLE T cells compared to non
      SLE controls. The number of mutations/polymorphisms in the 906 bp TCR zeta-chain
      3' untranslated region were significantly higher in SLE T cells compared to non
      SLE subjects (P = 0.032). Frequent mutations/polymorphisms and aberrant splicing
      of the downstream 3' untranslated region may affect the stability and/or
      transport of TCR zeta-chain mRNA, leading to its downregulation in SLE T cells.

PMID- 11247641
TI  - Autoantibodies in endometriosis sera recognize a Thomsen-Friedenreich-like
      carbohydrate antigen.
AB  - Autoantibody responses to endometrial antigens are a common feature of
      endometriosis. Antibody responses to a number of serum and tissue antigens such
      as alpha(2)-Heremans Schmidt glycoprotein (alpha(2)-HSG), transferrin, and
      carbonic anhydrase have been identified. The nature of the epitopes recognized on
      these proteins has not been determined. In this study we show that the serum
      antibody response to alpha(2)-HSG and carbonic anhydrase is against a common
      carbohydrate epitope which is also expressed on bovine fetuin. Removal of
      carbohydrate moieties from these antigens resulted in loss of antibody binding.
      Antibody reactivity with alpha(2)-HSG, fetuin and other antigens was removed by
      binding with the lectin jacalin. Jacalin specifically binds the Thomsen
      Friedenreich antigen (Galbeta1-3GalNAc). Demonstrating that the autoantibodies
      also reacted with other Thomsen-Friedenreich antigen-bearing proteins, serum IgA1
      and haemopexin confirmed an association with this epitope. These antigens have
      not been previously described as autoantigens in endometriosis and are of
      interest since they raise the possibility that this autoimmune response may
      either play a direct role in the disease process or reflect an abnormality of
      glycosylation in endometriosis. These results may also prove useful in the
      development of a serum diagnostic test for endometriosis.

PMID- 11247642
TI  - Induction of natural autoantibody activity following treatment of human
      immunoglobulin with dissociating agents.
AB  - Treatment of normal polyclonal human IgG and of F(ab')2 fragments of IgG with 6.0
      M urea, 1.3 M sodium thiocyanate or with acidic buffers (pH 2.0), resulted in a
      dramatic and selective enhancement of the preexisting antibody reactivity with
      self antigens. Enhanced antibody activity revealed by the dissociating agents was
      inhibited by the addition of an excess of the relevant soluble antigen. Human
      monoclonal IgG, including four different IgG1m(1) V(H)3+ and V(K)3+ paraproteins
      differing only in their CDRs, exhibited different changes in reactivity following
      urea treatment indicating major involvement of CDR sequences. The calculated
      dissociation constant of the binding reaction of normal IgG to the self antigen
      actin was 10(-6) M, whether IgG had been treated or not, indicating that the
      treatment increased the proportion of available self-reactive molecules instead
      of increasing the affinity of the preexisting natural autoantibodies. Enhanced
      autoreactivity was not due to aggregation of Ig, unmasking of the antibody site
      by removal of low MW antigens, nor to the denaturation of natural Id-anti-Id
      complexes. Taken together, these results suggest that treatment of Ig with
      dissociating agent results in the exposure of basic polyreactive antibody
      structures. The enhancement of reactivity may be of relevance in physiology of
      mucosal immunity and in therapeutic immunomodulation.

PMID- 11247643
TI  - Functional heterogeneity of inferior frontal gyrus is shaped by linguistic
      experience.
AB  - A crosslinguistic, positron emission tomography (PET) study was conducted to
      determine the influence of linguistic experience on the perception of segmental
      (consonants and vowels) and suprasegmental (tones) information. Chinese and
      English subjects (10 per group) were presented binaurally with lists consisting
      of five Chinese monosyllabic morphemes (speech) or low-pass-filtered versions of
      the same stimuli (nonspeech). The first and last items were targeted for
      comparison; the time interval between target tones was filled with irrelevant
      distractor tones. A speeded-response, selective attention paradigm required
      subjects to make discrimination judgments of the target items while ignoring
      intervening distractor tones. PET scans were acquired for five tasks presented
      twice: one passive listening to pitch (nonspeech) and four active (speech =
      consonant, vowel, and tone; nonspeech = pitch). Significant regional changes in
      blood flow were identified from comparisons of group-averaged images of active
      tasks relative to passive listening. Chinese subjects show increased activity in
      left premotor cortex, pars opercularis, and pars triangularis across the four
      tasks. English subjects, on the other hand, show increased activity in left
      inferior frontal gyrus regions only in the vowel task and in right inferior
      frontal gyrus regions in the pitch task. Findings suggest that functional
      circuits engaged in speech perception depend on linguistic experience. All
      linguistic information signaled by prosodic cues engages left-hemisphere
      mechanisms. Storage and executive processes of working memory that are implicated
      in phonological processing are mediated in discrete regions of the left frontal
      lobe.

PMID- 11247644
TI  - Knowledge-based inferencing after childhood head injury.
AB  - Inferencing was studied with a story comprehension task that required inferences
      to be made from a controlled knowledge base. Despite similar rates of knowledge
      base acquisition, knowledge base retention, and speeded access to the knowledge
      base across groups, the 18 children with severe head injury had lower rates of
      inferencing than the 15 children with mild head injury or the 18 age-matched
      controls. Results suggest that cognitive functions such as working memory and
      metacognitive skill that are disrupted by severe head injury may also play a role
      in some of the text- and discourse-level deficits commonly reported in these
      children, notably those involving inferencing.

PMID- 11247645
TI  - Contextual influences on phonetic identification in aphasia: the effects of
      speaking rate and semantic bias.
AB  - Two experiments examined the influence of context on stop-consonant voicing
      identification in fluent and nonfluent aphasic patients and normal controls.
      Listeners were required to label the initial stop in a target word varying along
      a voice onset time (VOT) continuum as either voiced or voiceless ([b]/[p] or
      [d]/[t]). Target stimuli were presented in sentence contexts in which the rate of
      speech of the sentence context (Experiment 1) or the semantic bias of the context
      (Experiment 2) was manipulated. The results revealed that all subject groups were
      sensitive to the contextual influences, although the extent of the context
      effects varied somewhat across groups and across experiments. In addition, a
      number of patients in both the fluent and nonfluent aphasic groups could not
      consistently identify even endpoint stimuli, confirming phonetic categorization
      impairments previously shown in such individuals. Results are discussed with
      respect to the potential reliance by aphasic patients on higher level context to
      compensate for phonetic perception deficits.

PMID- 11247646
TI  - Does dyslexia develop from learning the alphabet in the wrong hemisphere? A
      cognitive neuroscience analysis.
AB  - A new perspective is described which views developmental dyslexia as the outcome
      of learning to write the alphabet in the nondominant (right) hemisphere. The
      letter-level and whole-word subtypes of dyslexia are seen as differing responses
      adopted to cope with this predicament. Striking similarities between dyslexics
      and callosotomy patients in the allocation of covert attention to lateralized
      stimuli provide direction for integrating a diversity of dyslexic research within
      this framework. This synthesis, together with information from pure alexia, brain
      activation, and reading research, lends insight into the neural circuitry of the
      compensatory strategies adopted by the two dyslexic subtypes.

PMID- 11247647
TI  - Supra- and infrasylvian conduction aphasia.
AB  - Fifteen cases of conduction aphasia which were tested with the Aachen Aphasia
      Test (AAT), are presented. The CT lesion data were transformed to a standard 3D
      reference brain referring to the ACPC line. According to the lesion profiles a
      group of 6 patients had pure suprasylvian lesions, a group of 4 patients had pure
      infrasylvian lesions, and a group of 5 patients had lesions in both supra- and
      infrasylvian regions. Suprasylvian conduction aphasics are superior to
      infrasylvian conduction aphasics in the token test and in repetition tasks.
      Infrasylvian conduction aphasics use more stereotypes in spontaneous speech than
      suprasylvian conduction aphasics. Conduction aphasics with both lesion sites
      perform less well in tests of naming, writing, and comprehension than the pure
      types. Thus conduction aphasia is a heterogeneous syndrome anatomically and
      linguistically.

PMID- 11247648
TI  - Early and late mismatch negativity elicited by words and speech-like stimuli in
      children.
AB  - In auditory perception the brain's attentional and preattentional mechanisms
      select certain stimuli for preferential processing and filter out irrelevant
      input. This study investigated nonattentive auditory processing in children.
      Event-related potentials (ERPs) provide a means to study neural correlates
      related to language and speech-sound processing. Mismatch negativity (MMN) is an
      ERP wave that indicates attention-independent perceptual change detection. In
      this study cortical ERPs were elicited by complex tones, naturally spoken words,
      and pseudowords, with each stimulus type containing equal acoustical elements.
      Tones elicited a bifurcated mismatch negativity (MMN), with early MMN (peaking at
      150-200 ms) being more dominant. On the other hand, words elicited a strong late
      MMN, peaking at about 400-450 ms after stimulus onset. The MMN wave form was
      significantly weaker for pseudowords than for words. The late MMN wave,
      especially for word differences, was found to reflect summating MMN generators
      and memory trace formation on gestalt bases. Results suggest that the auditory
      processing, even nonattended, is highly associated with the cognitive meaning of
      the stimuli.

PMID- 11247649
TI  - Linking sight and sound: fMRI evidence of primary auditory cortex activation
      during visual word recognition.
AB  - We describe two studies that used repetition priming paradigms to investigate
      brain activity during the reading of single words. Functional magnetic resonance
      images were collected during a visual lexical decision task in which nonword
      stimuli were manipulated with regard to phonological properties and compared to
      genuine English words. We observed a region in left-hemisphere primary auditory
      cortex linked to a repetition priming effect. The priming effect activity was
      observed only for stimuli that sound like known words; moreover, this region was
      sensitive to strategic task differences. Thus, a brain region involved in the
      most basic aspects of auditory processing appears to be engaged in reading even
      when there is no environmental oral or auditory component.

PMID- 11247652
TI  - Semantic cueing effects on word retrieval in aphasic patients with lexical
      retrieval deficit.
AB  - We examined lexical access in word production, focusing on lexical retrieval
      deficit in aphasic patients. These patients were asked to name one picture at a
      time and we investigated how semantic cueing affected their ability to retrieve
      the word. When the subjects experienced a retrieval failure, they were presented
      with one type of cue, and then they tried to name the target picture again. Four
      types of cues were used: phonological, semantic related, semantic category
      member, and baseline cue. Both phonological and semantically related cues
      improved performance. In contrast, category member cues had no effects on
      releasing the retrieval block. These results can be explained by an interactive
      activation model in word production (Dell & O'Seaghdha, 1991).

PMID- 11247654
TI  - Multifactorial processes in recovery from aphasia: developing the foundations for
      a multileveled framework.
AB  - This paper develops the foundations for a framework of recovery from aphasia
      which attempts to integrate knowledge from several domains to form a basis for an
      approach to treatment as managed recovery. We still have a mainly operational
      appreciation of recovery derived from atheoretical group investigations using
      psychometric batteries and generic definitions of aphasia and a lack of clarity
      in the use of the terms restoration, compensation, and reorganization. There is a
      failure to appreciate the interrelation of different levels (e.g., neural,
      cognitive, behavioral) and the importance of different perceptions (e.g.,
      patient, relative, clinician) in individual recovery. The multileveled framework
      may improve understanding of what underlies individual recovery and form a
      framework for mapping interactions between levels as a basis for intervention.

PMID- 11247653
TI  - Memory and encoding of spoken discourse following right hemisphere damage:
      evidence from the Auditory Moving Window (AMW) technique.
AB  - We investigated the hypotheses that impaired discourse processing following right
      hemisphere damage is mediated by task difficulty and is associated with deficits
      in discourse encoding. Spoken discourse passages differing in contextual
      predictability were presented to right hemisphere-damaged (RHD) patients and to
      non-brain-damaged (NBD) controls for subsequent recall using the Auditory Moving
      Window paradigm. To manipulate processing difficulty, speech segments were of
      normal or accelerated speech rates. The recall results showed that RHD adults
      recalled less than NBD controls overall and failed to recall major idea units
      better than minor idea units for high predictability passages presented at
      accelerated speech rates. Both RHD patients and NBD controls failed to recall
      major idea units better than minor idea units for low predictability passages,
      regardless of speech rate. The encoding results showed that RHD adults were both
      slower overall and differentially slower than NBD controls when listening to
      accelerated passage segments. Taken together, the encoding and recall results are
      consistent with the view that extracting passage gist under difficult listening
      conditions is especially vulnerable for patients with right hemisphere strokes.

PMID- 11247655
TI  - Acquisition of new "words" in normal subjects: a suggestion for the treatment of
      anomia.
AB  - The study explores the efficacy of three learning methods in normal controls.
      Thirty subjects, randomly assigned to the repetition, reading aloud, or
      orthographic cueing method, were asked to learn 30 new "words" (legal nonwords
      arbitrarily assigned to 30 different pictures); 30 further new "words" were used
      as controls. Number of trials to criterion was significantly lower, and number of
      words remembered at follow-up was significantly higher for the orthographic
      cueing method. Two aphasic patients with damage to the output lexicons were also
      rehabilitated with the same three methods. In both patients the orthographic
      cueing method was significantly more efficacious. The differences in learning
      efficacy of the three methods are discussed.

PMID- 11247656
TI  - The N400 component in parents of children with specific language impairment.
AB  - Children with specific language impairment (SLI) often have a family history of
      language disorder. In this study, ERPs in response to a visual semantic priming
      task were recorded in parents of children with SLI. Despite equal performance,
      the ERPs displayed differences in language processing: larger N400 amplitudes
      indicated that the parents, especially the fathers, were less primed by the
      preceding context. Difference waveforms showed that the fathers of SLI children,
      contrary to controls, had less differentiated responses to congruent versus
      incongruent sentences. We propose that the N400 observations may be residual
      markers of past language deficiencies in the fathers. No differences in the N400
      effect were found in the mothers of SLI children.

PMID- 11247657
TI  - Neuropragmatics: extralinguistic communication after closed head injury.
AB  - This work is concerned with the decay of communicative abilities after head
      trauma. A protocol composed of 16 videotaped scenes was devised in order to
      investigate the comprehension of several types of communicative actions realized
      with extralinguistic means, like pointing or clapping. The protocol was
      administered to 30 closed-head-injured individuals. The results showed that
      performance decreased from simple standard acts to complex standard acts,
      deceits, and ironies. The subjects' performance was worse with the scenes
      reproducing failing, rather than successful, communicative actions. The results
      are compared with those we previously obtained with a linguistic protocol. A
      theory of the cognitive processes underlying intentional communication is
      outlined and used to explain the results.

PMID- 11247658
TI  - Relating selective brain damage to impairments with voicing contrasts.
AB  - Research is reviewed concerning the performance of several neurological groups on
      the perception and production of voicing contrasts in speech. Patients with
      cerebellar damage, Parkinson's disease, specific language impairment, Broca's
      aphasia, apraxia, and Wernicke's aphasia have been reported to be impaired in the
      perception and articulation of voicing. The types of deficits manifested by these
      neurologically impaired groups in creating and discriminating voicing contrasts
      are discussed and the respective contributions of separate neural areas are
      identified. A model is presented specifying the level of phonemic processing
      thought to be impaired for each patient group and critical tests of the model's
      predictions are identified.

PMID- 11247659
TI  - The anatomy of auditory word processing: individual variability.
AB  - This study used functional magnetic resonance imaging (fMRI) to investigate the
      neural substrate underlying the processing of single words, comparing activation
      patterns across subjects and within individuals. In a word repetition task,
      subjects repeated single words aloud with instructions not to move their jaws. In
      a control condition involving reverse speech, subjects heard a digitally reversed
      speech token and said aloud the word "crime." The averaged fMRI results showed
      activation in the left posterior temporal and inferior frontal regions and in the
      supplementary motor area, similar to previous PET studies. However, the
      individual subject data revealed variability in the location of the temporal and
      frontal activation. Although these results support previous imaging studies,
      demonstrating an averaged localization of auditory word processing in the
      posterior superior temporal gyrus (STG), they are more consistent with
      traditional neuropsychological data, which suggest both a typical posterior STG
      localization and substantial individual variability. By using careful head
      restraint and movement analysis and correction methods, the present study further
      demonstrates the feasibility of using overt articulation in fMRI experiments.

PMID- 11247661
TI  - Genetic diversity of the human serotonin receptor 1B (HTR1B) gene.
AB  - We systematically and comprehensively investigated polymorphisms of the HTR1B
      gene as well as their linkage disequilibrium and ancestral relationships. We have
      detected the following polymorphisms in our sample via denaturing gradient gel
      electrophoresis, database comparisons, and/or previously published assays: G
      511T, T-261G, -182INS/DEL-181, A-161T, C129T, T371G, T655C, C705T, G861C, A1099G,
      G1120A, and A1180G. The results of the intermarker analyses showed strong linkage
      disequilibrium between the C129T and the G861C polymorphisms and revealed four
      common haplotypes: ancestral (via chimpanzee comparisons), 129T/861C, -161T, and 
      182DEL-181. The results of association tests with schizophrenia were negative,
      although A-161T had a nominal P = 0.04 via ASPEX/sib_tdt. The expressed missense
      substitutions, Phe124Cys, Phe219Leu, Ile367Val, and Glu374Lys, could potentially
      affect ligand binding or interaction with G proteins and thus modify drug
      response in carriers of these variants. On average, the human cSNPs and
      differences among other primates clustered in the more thermodynamically unstable
      regions of the mRNA, which suggests that the evolutionary survival of nucleotide
      sequence variation may be influenced by the mRNA structure of this gene.

PMID- 11247662
TI  - Linkage and allelic association of chromosome 5 cytokine cluster genetic markers
      with atopy and asthma associated traits.
AB  - Linkage and association of polymorphic markers in the chromosome 5q31-q33
      cytokine cluster to atopy and asthma associated phenotypes have been reported by
      a number of groups. To investigate this region, 29 polymorphic markers were used
      to genotype a combined set of 233 families. These markers were ordered based upon
      the genetic data, supplemented by published genetic and physical maps.
      Significant two-point linkage was observed for asthma (most significant marker
      IRF1, P = 0.0002) and atopy (CD14SNP, P = 0.0001). Allelic association was
      observed between D5S463 and atopy (P = 0.002) and the skin prick test index (P =
      0.04). The data support the possibility of three asthma/atopy loci in the 5q31
      q33 region, each with a relatively small effect.

PMID- 11247663
TI  - Axonemal beta heavy chain dynein DNAH9: cDNA sequence, genomic structure, and
      investigation of its role in primary ciliary dyskinesia.
AB  - Dyneins are multisubunit protein complexes that couple ATPase activity with
      conformational changes. They are involved in the cytoplasmatic movement of
      organelles (cytoplasmic dyneins) and the bending of cilia and flagella (axonemal
      dyneins). Here we present the first complete cDNA and genomic sequences of a
      human axonemal dynein beta heavy chain gene, DNAH9, which maps to 17p12. The 14
      kb-long cDNA is divided into 69 exons spread over 390 kb. The cDNA sequence of
      DNAH9 was determined using a combination of methods including 5' rapid
      amplification of cDNA ends, RT-PCR, and cDNA library screening. RT-PCR using
      nasal epithelium and testis RNA revealed several alternatively spliced
      transcripts. The genomic structure was determined using three overlapping BACs
      sequenced by the Whitehead Institute/MIT Center for Genome Research. The
      predicted protein, of 4486 amino acids, is highly homologous to sea urchin
      axonemal beta heavy chain dyneins (67% identity). It consists of an N-terminal
      stem and a globular C-terminus containing the four P-loops that constitute the
      motor domain. Lack of proper ciliary and flagellar movement characterizes primary
      ciliary dyskinesia (PCD), a genetically heterogeneous autosomal recessive
      disorder with respiratory tract infections, bronchiectasis, male subfertility,
      and, in 50% of cases, situs inversus (Kartagener syndrome, KS). Dyneins are
      excellent candidate genes for PCD and KS because in over 50% of cases the
      ultrastructural defects of cilia are related to the dynein complex. Genotype
      analysis was performed in 31 PCD families with two or more affected siblings
      using a highly informative dinucleotide polymorphism located in intron 26 of
      DNAH9. Two families with concordant inheritance of DNAH9 alleles in affected
      individuals were observed. A mutation search was performed in these two
      "candidate families," but only polymorphic variants were found. In the absence of
      pathogenic mutations, the DNAH9 gene has been excluded as being responsible for
      autosomal recessive PCD in these families.

PMID- 11247664
TI  - Whole-body gene expression by data mining.
AB  - To date, a comprehensive survey of the expression of lysyl oxidase (LOX), lysyl
      oxidase-like 1 (LOXL1), and lysyl oxidase-like 2 (LOXL2) has yet to be performed.
      The use of in vitro strategies to accomplish this task would prove daunting as it
      is both time-consuming and costly. We present a new in silico data mining
      strategy that directly addresses these limitations. Sequences corresponding to
      the 3' untranslated regions of LOX, LOXL1, and LOXL2 were individually queried
      against the human expressed sequence tag database (dbEST). In this manner, the
      entire tissue repertoire available in the dbEST was surveyed. This provided an
      estimate of the levels of mRNA transcripts in a variety of adult and fetal
      tissues. We have also employed this strategy to determine the pattern of
      expression and levels of a newly discovered gene, CGI-15. The veracity of this
      technique has been independently assessed by semiquantitative PCR analysis. The
      application of this technology is bounded only by the ever-growing information
      available in the GenBank, UniGene, and human EST databases. The utility of our
      data mining strategy to establish relative transcript levels in numerous tissues
      is presented.

PMID- 11247665
TI  - Cloning and characterization of SLC26A6, a novel member of the solute carrier 26
      gene family.
AB  - The SLC26 gene family (solute carrier family 26) comprises five mammalian genes
      that encode anion transporter-related proteins. In addition to sat-1 and prestin,
      which were cloned from rat and gerbil, respectively, three human members have
      been identified and associated with specific genetic diseases (DTD, diastrophic
      dysplasia; CLD, congenital chloride diarrhea; PDS, Pendred syndrome). In this
      study we used a homology approach combined with RACE PCR to identify human
      SLC26A6, the sixth member of this gene family. Northern blot analysis showed the
      highest SLC26A6 transcript levels in kidney and pancreas. Expression in MDCK
      cells and in Xenopus oocytes demonstrated trafficking of the SLC26A6 protein to
      the cell membrane but did not reveal anion transport activity with tracer uptake
      or intracellular pH measurements. We determined the genomic structure of the
      SLC26A6 gene and excluded mutations in the 21 coding exons as the cause of DFNB6
      and USH2B, which closely map to the SLC26A6 chromosomal locus (3p21).

PMID- 11247666
TI  - High-resolution mapping of the blood pressure QTL on chromosome 7 using Dahl rat
      congenic strains.
AB  - It was previously shown using Dahl salt-sensitive (S) and salt-resistant (R) rats
      that a blood pressure quantitative trait locus (QTL) was present on rat
      chromosome 7. In the present work, this QTL was localized to a region less than
      0.54 cM in size on the linkage map using a series of congenic strains. This
      region was contained in a single yeast artificial chromosome that was 220 kb
      long. This small segment still contained the primary candidate locus Cyp11b1
      (11beta-hydroxylase), but the adjacent candidate genes Cyp11b2 (aldosterone
      synthase) and Cyp11b3 were ruled out. It is concluded that 11beta-hydroxylase,
      through its known genetic variants altering the production of 18-hydroxy-11-deoxy
      corticosterone, is very likely to account for the blood pressure QTL on
      chromosome 7 in the Dahl rat model of hypertension. This QTL accounts for about
      23 mm Hg under the condition of 2% NaCl diet for 24 days.

PMID- 11247667
TI  - A double-deletion mutation in the Pitx3 gene causes arrested lens development in
      aphakia mice.
AB  - The recessive aphakia (ak) mouse mutant is characterized by bilateral
      microphthalmia due to a failure of lens morphogenesis. We fine-mapped the ak
      locus to the interval between D19Umi1 and D19Mit9, developed new polymorphic
      markers, and mapped candidate genes by construction of a BAC contig. The Pitx3
      gene, known to be expressed in lens primordia, shows zero recombination with the
      ak mutation on our intersubspecific intercross panel representing 1170 meioses. A
      recent report described a deletion in the intergenic region between Gbf1 and
      Pitx3 as the possible ak mutation. Our results differ in that we find not only
      the distant intergenic deletion, but also a much larger deletion directly in the
      Pitx3 gene, eliminating exon 1 and extending into intron 1 and the promoter
      region. Pitx3 transcript levels are severely reduced in ak/ak mice from E11.5 to
      newborn (5 +/- 1% of the wildtype levels at E13.5), while an involvement of the
      flanking Gbf1 and Cig30 genes in the aberrant lens development is highly unlikely
      based on expression analysis. We conclude that the ak mutation consists of two
      deletions, the larger of which removes part of Pitx3, indicating a crucial role
      of this gene in early lens development.

PMID- 11247668
TI  - A chromosome 15 quantitative trait locus controls levels of radiation-induced
      jejunal crypt cell apoptosis in mice.
AB  - Jejunal crypt cells undergo apoptosis in response to ionizing radiation exposure.
      In mice the number of cells deleted by apoptosis is determined by several factors
      including the dose of radiation, the time of day the apoptosis level is
      quantified, and the strain of mouse irradiated. We previously found that the
      difference in radiation-induced apoptosis levels between C57BL/6J (B6) and
      C3Hf/Kam (C3H) mice is controlled by multiple genes, and this set of genes is
      distinct from that controlling thymocyte apoptosis levels in the same strain
      combination. Here, we report that a new quantitative trait locus on chromosome
      15, Rapop5, partly accounts for the murine strain difference in susceptibility to
      radiation-induced jejunal crypt cell apoptosis. In addition, we show sexual
      dimorphism in the extent of radiation-induced jejunal crypt cell apoptosis, with
      female mice having higher levels.

PMID- 11247669
TI  - Disruption of Apc10/Doc1 in three alleles of oligosyndactylism.
AB  - Oligosyndactylism (Os) is a radiation-induced mouse mutation associated with
      recessive lethality and a dominant effect on limb and kidney development. The
      lethal effect of the mutation is due to a cell-autonomous block in the transition
      from metaphase to anaphase. We have previously characterized two transgene
      induced mutations, 94-A and 94-K, which are allelic with Os. These mutations
      facilitated the identification of genomic segments and transcribed sequences in
      the affected region. One of the transcripts in this region corresponds to the
      mouse homolog of the anaphase-promoting complex component APC10/DOC1. The
      disruption of this gene can explain the mitotic arrest phenotype of all three
      alleles of Os.

PMID- 11247670
TI  - Identification of mesoderm development (mesd) candidate genes by comparative
      mapping and genome sequence analysis.
AB  - The proximal albino deletions identify several functional regions on mouse
      Chromosome 7 critical for differentiation of mesoderm (mesd), development of the
      hypothalamus neuroendocrine lineage (nelg), and function of the liver (hsdr1).
      Using comparative mapping and genomic sequence analysis, we have identified four
      novel genes and Il16 in the mesd deletion interval. Two of the novel genes,
      mesdc1 and mesdc2, are located within the mesd critical region defined by BAC
      transgenic rescue. We have investigated the fetal role of genes located outside
      the mesd critical region using BAC transgenic complementation of the mesd early
      embryonic lethality. Using human radiation hybrid mapping and BAC contig
      construction, we have identified a conserved region of human chromosome 15
      homologous to the mesd, nelg, and hsdr1 functional regions. Three human diseases
      cosegregate with microsatellite markers used in construction of the human BAC/YAC
      physical map, including autosomal dominant nocturnal frontal lobe epilepsy
      (ENFL2; also known as ADNFLE), a syndrome of mental retardation, spasticity, and
      tapetoretinal degeneration (MRST); and a pyogenic arthritis, pyoderma
      gangrenosum, and acne syndrome (PAPA).

PMID- 11247671
TI  - Synergy between tetA and rpsL provides high-stringency positive and negative
      selection in bacterial artificial chromosome vectors.
AB  - Bacterial artificial chromosome (bacmid) vectors are used to stably propagate
      large, complex fragments of cloned DNA and are a core technology for functional
      genomics. The simplest method of analyzing bacmid clones would involve a direct
      mutagenesis or allele exchange protocol utilizing positive and negative
      selectable markers. The utility of three different negative selectable markers to
      function in the context of a bacmid vector was therefore investigated: sacB from
      Bacillus subtilis, which confers sensitivity to sucrose; tetA from TN10, which
      confers resistance to tetracycline, osmotic sensitivity, and sensitivity to
      kanamycin and streptomycin; and rpsL from Escherichia coli, which confers
      sensitivity to streptomycin. When expressed individually in the context of a
      bacmid vector, each of these markers confers a similar stringency of negative
      selection, with plating efficiencies on selective media of 2.3 x 10(-5), 9.4 x
      10(-4), and 5.7 x 10(-5), respectively. However coexpression of rpsL and tetA
      results in a synergistic enhancement of the osmotic, kanamycin, and streptomycin
      sensitivities, with a stringency of selection of approximately 50- to
      approximately 1000-fold over that obtained with rpsL or tetA alone and
      approximately 20-fold more than that obtained using sacB. The combination of rpsL
      and tetA thus serves as the most efficient positive and negative selectable
      marker system described to date.

PMID- 11247673
TI  - Frequent germline deletion polymorphism of chromosomal region 8p12-p21 identified
      as a recurrent homozygous deletion in human tumors.
AB  - A number of carcinomas show high frequency of loss of heterozygosity (LOH) at
      chromosome 8p, suggesting that putative tumor suppressor genes are present in
      this region. While searching for homozygous deletions in a panel of pancreatic
      and biliary tumors, we discovered a homozygous deletion at the microsatellite
      AFMa224wh5 in chromosome region 8p12-p21. We applied a six-step algorithm
      comprising germline analysis, breakpoint sequencing, population screening, online
      gene mapping, allelic discrimination of tumor-associated LOH, and family history
      analysis. The results indicated that the deletion was likely due to a normal 102
      bp deletion polymorphism present in nearly 10% of the study population, not
      likely to involve a recessive cancer-associated gene. Researchers need to be
      aware that germline insertion/deletion polymorphisms can affect the results of
      positional cloning efforts in human neoplasms. This problem would be accentuated
      in studies of cell lines where a paired sample of constitutional DNA is often
      unavailable.

PMID- 11247672
TI  - A sequence-ready map of the human chromosome 1q telomere.
AB  - A 260-kb half-YAC clone derived from human chromosome 1q was mapped at high
      resolution using cosmid subclone fingerprint analysis and was integrated with
      overlapping clones from the telomeric end of a separately derived 1q44 BAC contig
      to create a sequence-ready map extending to the molecular telomere of 1q.
      Analysis of 100 kb of sample sequences from across the 260-kb region encompassed
      by the half-YAC revealed the presence of EST sequence matches corresponding to 12
      separate Unigene clusters and to 12 separate unclustered EST sequences. Low-copy
      subtelomeric repeats typical of many human telomere regions are present within
      the distal-most 30 kb of 1q. The previously isolated and radiation hybrid-mapped
      markers Bda84F03, 1QTEL019, and WI11861 localized at distances approximately 32,
      88, and 99 kb, respectively, from the 1q terminus. This sequence-ready map
      permits high-resolution integration of genetic maps with the DNA sequences
      directly adjacent to the tip of human chromosome 1q and will enable telomeric
      closure of the human chromosome 1q DNA reference sequence by connecting the
      molecular 1q telomere to an internal BAC contig.

PMID- 11247674
TI  - Molecular cloning of a novel member of the GLUT family of transporters, SLC2a10
      (GLUT10), localized on chromosome 20q13.1: a candidate gene for NIDDM
      susceptibility.
AB  - Non-insulin-dependent diabetes mellitus (NIDDM) is a multifactoral disease with
      both environmental and genetics causes. Genome-wide screening procedures have
      identified several susceptibility loci for NIDDM within the human genome. We
      describe the cloning of a putative sugar transporter that has been localized to
      human chromosome 20q12-q13.1, one of the genomic loci associated with NIDDM.
      Because of the strong resemblance of this novel protein to members of the
      mammalian facilitative glucose transporter family (GLUT), we refer to the protein
      as GLUT10 (HGMW-approved gene symbol SLC2A10). GLUT10 contains 541 amino acids
      with several glucose transporter sequence motifs and amino acids essential for
      glucose transport function. In addition, secondary structure analysis of GLUT10
      predicts 12 putative transmembrane domains, a hallmark structure of the GLUT
      family. The tissue distribution of GLUT10 was determined by Northern analysis,
      which revealed highest levels of expression in the liver and pancreas. From these
      data, we believe that the chromosomal localization, tissue distribution, and
      predicted function make GLUT10 an excellent candidate for a susceptibility gene
      involved in NIDDM.

PMID- 11247675
TI  - Infection control in the Netherlands.

PMID- 11247676
TI  - The effectiveness of interventions aimed at increasing handwashing in healthcare
      workers - a systematic review.
AB  - Handwashing is widely accepted as being key to the prevention of hospital
      acquired infection but the frequency of handwashing by healthcare workers has
      been found to be low. A systematic critical literature review was conducted to
      establish the effectiveness of interventions aimed at increasing compliance with
      handwashing in healthcare workers. The results showed that one-off educational
      interventions have a very short-term influence on handwashing behaviour. Use of
      strategically placed reminders, or asking patients to remind staff of the need to
      conduct handwashing can have a modest but more sustained effect. Feedback of
      performance can increase levels of handwashing but if feedback is not repeated
      regularly, then this effect is not maintained over long periods. Automated sinks
      increase the quality of handwashing but healthcare workers can be discouraged
      from using these because of the additional time involved. Provision of
      moisturized soaps appears to make little difference to handwashing behaviour but
      providing 'dry' hand rubs near patient beds may lead to a minimal increase in the
      frequency with which staff decontaminate their hands. Multifaceted approaches
      which combine education with written material, reminders and continued feedback
      of performance can have an important effect on handwashing compliance and rates
      of hospital-acquired infection.

PMID- 11247677
TI  - Investigation of aciclovir-resistant herpes simplex virus I infection in a bone
      marrow transplantation unit: genotyping shows that different strains are
      involved.
AB  - Over an eight-month period from October 1997 to May 1998, four patients who had
      received a bone marrow transplant (BMT) from an unrelated donor presented with
      severe mucosal cutaneous infections involving aciclovir resistant herpes simplex
      virus 1 (HSV-1). The emergence within a short period of resistant HSV-1 strains
      in the bone marrow transplantation unit raised fears of hospital-acquired
      infections. The hypothesis was investigated by restriction fragment length
      polymorphism (RFLP), sequencing of the thymidine kinase (TK) gene and genotyping
      of hypervariable regions of these four strains. Restriction fragment length
      polymorphism proved to be poorly discriminant and the TK sequence did not rule
      out transmission between these patients. Amplification of reiterating
      hypervariable genomic HSV-1 regions designated Re IV and Re VII clearly
      differentiated patients' strains. Thus, in this study, there was no evidence of
      nosocomial transmission of HSV-1 strains between the four patients.

PMID- 11247678
TI  - Chryseobacterium (Flavobacterium) meningosepticum outbreak associated with
      colonization of water taps in a neonatal intensive care unit.
AB  - From September 1994 to May 1996, a strain of multi-resistant Chryseobacterium
      (Flavobacterium) meningosepticum was isolated from eight neonates on a neonatal
      intensive care unit. The strain was resistant to ampicillin, ceftazidime,
      imipenem, gentamicin, ciprofloxacin and trimethoprim-sulphamethoxazole,
      susceptible to piperacillin and amikacin, and had variable susceptibility to
      rifampicin and vancomycin. Two neonates were infected (one had pneumonia and one
      septicaemia and meningitis); the remaining six neonates were colonized in the
      respiratory secretions. Two cases occurred that could not be explained by cross
      infection during the outbreak. Environmental screening recovered C.
      meningosepticum from sink taps. Pulsed-field gel electrophoresis of chromosomal
      macrorestriction digests of patient and environmental isolates showed them to be
      representatives of a single strain. The outbreak was controlled after staff were
      required to use an alcoholic handrub after washing hands, and toiletting of
      babies was done with sterile water instead of tap-water. Repair and chlorination
      of the water-tanks and changing the sink-taps resolves the outbreak.

PMID- 11247679
TI  - Microbiological screening of post-mortem bone donors - two case reports.
AB  - This study assesses the value of blood cultures in combination with swab
      culturing techniques in association with bone banking procedures. The results of
      blood and swab cultures of two postmortem bone donors were compared with procured
      grafts, cultured in their entirety. In one donor, who died of drowning, three of
      the 12 entire graft cultures were positive with the same microorganism of high
      pathogenicity as the blood culture, whilst the swab culture of only one graft was
      positive. In the second donor, who died from myocardial infarction, four entire
      cultures were positive with the same organism of high pathogenicity as the blood
      culture, whilst the swab cultures of three grafts were positive. In both donors
      identical organisms were cultured from the myocardium of the pulmonary or aortic
      heart valve. The results confirm the limited sensitivity of swab culturing
      techniques. Especially micro-organisms inside a graft, disseminated through the
      bloodstream, can remain unnoticed. Blood cultures seem to provide additional
      information on micro-organisms that have spread haematogenously pre-mortem and
      may even provide information on the source from which they have spread.

PMID- 11247680
TI  - The rate and cost of hospital-acquired infections occurring in patients admitted
      to selected specialties of a district general hospital in England and the
      national burden imposed.
AB  - Between April 1994 and May 1995 4000 adult patients admitted to selected
      specialties of a district general hospital were recruited to this study. Hospital
      acquired infections presenting during the in-patient stay were identified using
      previously validated methods of surveillance, and information on daily resource
      use by both infected and uninfected patients was recorded and estimates of their
      cost derived. Linear regression modelling techniques were used to estimate how
      much of the observed variation in resource use and costs could be explained by
      the presence of an infection. Complete in-patient data sets were obtained for
      3980 patients. Of these, 309 patients (7.8%; 95% CI; 7.0, 8.6) presented with one
      or more hospital-acquired infections during the in-patient period. Infected
      patients, on average, incurred hospital costs 2.9 (regression model estimate:
      2.8; 95% CI; 2.6, 3.0) times higher than uninfected patients, equivalent to an
      additional pound3154 (regression model estimate pound2917). Both the incidence
      and the economic impact varied with site of infection and with admission
      specialty. Estimates of the burden of hospital-acquired infections occurring in
      adult patients admitted to similar specialties at NHS hospitals in England were
      derived from the results of this study. An estimated 320 994 (95% CI; 288 071,
      353 916) patients per annum acquire one or more infections which present during
      the in-patient period, and these infections cost the hospital sector an estimated
      930.62 million pounds (95% CI; 780.26 pounds; 1080.97 million pounds) per annum.
      The results presented represent the gross economic benefits that might accrue if
      these infections are prevented. Further research is required to establish the net
      benefits of prevention.

PMID- 11247681
TI  - Five-year surveillance of patients with communicable diseases nursed in
      isolation.
AB  - During a five year surveillance program of patients with communicable diseases
      nursed in isolation, we gathered information on 2880 patients who were nursed in
      isolation for 28 145 days, from January 1994 to December 1998. The mean number of
      patients nursed in isolation was 575.4 (range, 427-709) per year. On average 2.4%
      of patients admitted yearly to the University Medical Center (UMC) were nursed in
      isolation. The mean number of days nursed in isolation was 9.8 days per
      patient.1996 was a peak year in isolations due to outbreaks of gentamicin
      resistant enterobacteriaceae (GRB) and methicillin resistant Staphylococcus
      aureus (MRSA). The main reasons for requiring isolation were: GRB, MRSA (proven
      and suspected cases), Clostridium difficile, viral infections and Mycobacterium
      tuberculosis. Registration of quantitative data on nursing patients in isolation,
      as presented in this paper, makes it possible to gain insight into the type and
      number of isolation indications, the required isolation room capacity on
      different wards, the workload of healthcare workers resulting from isolation and
      the trends in incidence of communicable diseases.

PMID- 11247682
TI  - Lapses in measures recommended for preventing hospital-acquired infection.
AB  - This study was carried out in a rural tertiary care referral hospital in central
      India, to ascertain lapses made by people caring for neonates in measures
      recommended for preventing hospital-acquired infections. Unobtrusive observation
      of the healthcare personnel (doctors, nurses, mothers and hospital attendants)
      during care of the newborn was undertaken. Lapse in handwashing by healthcare
      personnel was observed around 41% of the time, although mothers practiced their
      instructions meticulously. Lapses in methods of hand drying were seen around 7-8%
      of the time, in those who did wash their hands. Gloves were not used around 21%
      of the time, when they should have been; and of those using gloves, they were
      unsterile in around 22% cases. At delivery babies were received unhygienically on
      approximately 67% of occasions observed. Lapses during cord care ranged from
      14.2% to 28.6% and during resuscitation from 16.6% to 60% of occasions. An
      uncleaned stethoscope was used 75% of the time. The practice of putting a finger
      in the baby's mouth was observed on 18 occasions. Considerable lapses by all, in
      every measure recommended for the prevention of hospital-acquired infections were
      observed. It is concluded that nothing other than an individual's commitment is
      likely to be successful in preventing hospital-acquired infections.

PMID- 11247683
TI  - Additional hospital stay and charges due to hospital-acquired infections in a
      neonatal intensive care unit.
AB  - A comparative retrospective cohort study was performed to evaluate the influence
      of hospital-acquired infection (HAI) in neonates on additional charges and
      hospital stay. Neonates admitted between October 1993 and discharged alive before
      December 1995 at the neonatal intensive care unit of a university hospital were
      studied. Of 515 neonates, 69 (13%) had one or more HAI; 45 (20 with proven HAI,
      25 with suspected HAI) were matched to 45 controls. After matching for
      gestational age, surgery, artificial ventilation and patent ductus arteriosus,
      central vascular catheter utilization was the only factor significantly
      associated with HAI. Charges were obtained from hospital discharge abstracts and
      the duration of hospitalization from patients' files. The mean additional length
      of hospital stay in neonates with HAI was 24 days (54 days vs. 30 days, P= 0.002)
      but did not differ significantly in patients with proven or suspected HAI (67
      days vs. 51 days, P> 0.05). The mean extra charges for patients with a HAI were
      11 750 EURO (9635 pounds). Accommodation accounted for 72%, fees for 22%,
      pharmaceuticals for 5% and ancillary items for 1% of these extra charges. The
      mean charges per day were similar for controls [443 EURO (363 pounds)] and HAI
      patients [453 EURO (372 pounds)]. Overall charges and charges per day were
      similar for neonates with proven and suspected HAI.

PMID- 11247684
TI  - Do plastic adhesive drapes prevent post caesarean wound infection?
AB  - We conducted a prospective randomized controlled double-blind trial at a regional
      referral centre for the Eastern Cape area, (Livingstone Hospital) to determine
      whether the use of plastic adhesive drapes intraoperatively would prevent Post
      Caesarean Section Wound Infection. A total of 620 patients undergoing Caesarean
      section (CS) were enrolled for randomization in the trial. Fifteen patients were
      excluded, while 305 received drapes (test group) and 300 did not (control group).
      Two patients in the control group were subsequently excluded. The primary outcome
      measure was the presence of Post Caesarean Wound Infection. A secondary outcome
      measure was the number of days in hospital post operation. The study and control
      groups were comparable at entry. Results show that 34 patients in the test group
      (N= 305) developed wound sepsis (11.1%) compared with 30 in the control group (N=
      298) (10.1%) (difference not significant; Fisher's exact test 0.6933). Average
      days spent in hospital postoperatively were similar for both test (infected
      cases: mean 10.56 SD 3.84; non-infected cases: mean 5.21 SD 1.3) and control
      groups (infected cases: mean 10.18 SD 3.81; non-infected cases: mean 5.2 SD 0.93)
      (NS). We concluded that the use of plastic adhesive skin drapes did not avert
      PCWS or decrease the length of post operative stay in hospital for septic cases.

PMID- 11247685
TI  - Could irrigation, debridement and antibiotic therapy cure an infection of a total
      hip arthroplasty?
AB  - Seven patients suffering from an acute (less than two weeks) infection of a total
      hip arthroplasty were treated by irrigation and debridement, with appropriate
      antibiotic therapy and retention of the prosthesis. They were followed for an
      average of 30 months. Infection did not recur in five (71%) patients, but the
      other two required further surgery. We conclude that a cure can be obtained by
      this method, although the results are inferior to re-implantation. A minimal
      procedure spares a patient the morbidity and cost of a more extensive operation.
      Higher success rates might have been achieved by selecting patients infected with
      organisms of low virulence, but there are insufficient data to predict whether
      this treatment would decrease the success of subsequent re-implantation.

PMID- 11247686
TI  - Candida colonization in mechanically ventilated patients.
AB  - The diagnosis of pulmonary candidosis is controversial. We undertook a
      prospective study on 50 mechanically ventilated (>48 h) patients who were
      hospitalized (>72 h) in the intensive care unit (ICU) with the aim of assessing
      the incidence of the isolation of Candida species from endotracheal aspirates
      (EA). Patients were categorized as individuals already colonized with Candida
      spp. on admission, individuals becoming colonized during hospitalization, or
      patients with no colonization. Patients in the ICU were hospitalized for a mean
      of 23 days. The percentage of patients already colonized with Candida was low
      (six of 50; 12%), the incidence of Candida isolation from EA in critically ill,
      mechanically ventilated patients in ICU was also low (six of 50; 12%). Age,
      duration of hospitalization, pre-treatment with antimicrobials or
      immunosuppressive agents and occurrence of underlying disease were not risk
      factors in our study. Both antifungal usage and neutropenia were more common in
      already colonized patients. No risk factors were determined for patients
      colonized during hospitalization. As all the isolates identified were C.
      albicans. It appears that at present, colonization and/or infection by more
      resistant Candida species is not a problem in our unit.

PMID- 11247687
TI  - Should health care workers in the tropics be immunized against varicella?
AB  - In tropical regions, chickenpox affects both adults and children. Therefore,
      healthcare workers in the tropics are vulnerable to hospital-acquired varicella
      infection and they may transmit infection to susceptible hospitalized
      individuals. Although the varicella vaccine is safe and effective, its cost is a
      deterrent to its use in routine immunization programmes. In order to assess
      whether vaccination of susceptible healthcare workers to prevent hospital
      acquired transmission may be justified, we have documented the frequency of
      varicella among healthcare workers in our hospital. There were 96 admissions for
      varicella during the 1993-1997 period; staff and student nurses accounted for
      76%. The peak season of admission was from February to April. The attack rate in
      staff and student nurses was 0.78 and 1.54 per 100 person-years, respectively.
      While community outbreaks of varicella occur in this region once in 4-5 years,
      hospital outbreaks of varicella occurred every year. This poses the risk of
      transmission to hospitalized patients, with serious consequences among
      immunocompromized individuals. Therefore, we recommend systematic selective
      vaccination of susceptible healthcare workers to break this cycle of annual
      varicella outbreaks among hospital personnel.

PMID- 11247688
TI  - Epidemiological characterization of hospital-acquired Acinetobacter baumannii
      isolates from a 1500-bed teaching hospital by phenotypic and genotypic methods.

PMID- 11247689
TI  - Decontamination of minimally invasive surgical endoscopes and accessories.

PMID- 11247692
TI  - The imaging of ischaemic stroke.
AB  - Stroke is a clinical syndrome of a rapidly developing focal neurological deficit
      that may be classified for practical purposes into ischaemic and haemorrhagic.
      The role of imaging is to exclude mimics of ischaemic stroke or intracranial
      haemorrhage and confirm the presence of an ischaemic stroke. Computed tomography
      (CT) remains the investigation of choice to exclude acute intracranial
      haemorrhage but diffusion weighted magnetic resonance (MR) has proved to be a
      sensitive method of detecting early ischaemic infarction. Perfusion weighted MR
      allows further assessment at the same examination that could help guide the
      clinician in the risk/benefit analysis of treatment with thrombolytics or
      neuroprotective agents under evaluation. This can also be achieved with CT. This
      review article discusses the imaging of ischaemic stroke, relating the
      pathophysiology of stroke to it. It deals separately in more detail with these
      newer MR techniques.

PMID- 11247693
TI  - Angiomatosis of bone and soft tissue: a spectrum of disease from diffuse
      lymphangiomatosis to vanishing bone disease in young patients.
AB  - The application of cross-sectional imaging in the investigation of patients with
      angiomatosis reveals that lymphangiomatosis and vanishing bone disease should not
      be considered as separate entities, but rather as a spectrum of disease. We
      present a pictorial review of eight patients demonstrating the manifestations of
      soft tissue and bony involvement. We highlight a subgroup of patients with
      chyloid pleural effusions who have a poor prognosis.

PMID- 11247694
TI  - Thoracic radiology.

PMID- 11247695
TI  - Thoracic computed tomography in patients with suspected malignant pleural
      effusions.
AB  - AIM: To assess the role of contrast-enhanced computed tomography (CT)
      prospectively in patients with suspected malignant pleural effusions. MATERIALS
      AND METHODS: Forty consecutive patients referred for the investigation of a
      suspected malignant pleural effusion had contrast-enhanced thoracic CT,
      thoracoscopy, thoraco-centesis and pleural biopsy, either percutaneously or at
      thoracoscopy. Final diagnoses were based on histopathological or cytological
      analysis (n = 30), autopsy findings (n = 3) or clinical follow-up (n = 7). The
      pleural surfaces were classified at contrast-enhanced CT as normal or abnormal
      and, if abnormal, as benign or malignant in appearance using previously
      established CT criteria for malignant pleural thickening by two observers unaware
      of the pathological diagnosis. RESULTS: Pleural effusions were malignant in 32
      patients and benign in eight patients. Pleural surfaces assessed at CT showed
      features of malignancy in 27 out of 32 patients with a malignant effusion
      (sensitivity 84%, specificity 100%). Overall, CT appearances indicated the
      presence of malignancy in 28 of 32 (87%) patients. All eight patients with benign
      pleural disease were correctly diagnosed by CT. CONCLUSION: Contrast-enhanced CT
      is of value in patients with suspected malignant pleural effusions. The
      previously established criteria for malignant pleural thickening of nodularity,
      irregularity and pleural thickness >1 cm are reliable in the presence of a
      pleural effusion.

PMID- 11247696
TI  - Distribution of intranodal vessels in differentiating benign from metastatic neck
      nodes.
AB  - AIM: Recent studies report high accuracy of power Doppler sonography in the
      differentiation of benign from malignant cervical lymphadenopathy. This study was
      undertaken to identify which of the parameters used in Doppler sonography of
      cervical lymph nodes is accurate and readily applicable in routine clinical
      practice. MATERIALS AND METHODS: We reviewed the power Doppler ultrasound
      examinations of 50 patients with cytologically proven metastatic nodes from
      nasopharyngeal carcinoma and 50 patients with proven reactive lymphadenopathy.
      All the examinations had been performed by an experienced sonologist, and
      intranodal vascular distribution and resistance were evaluated during real-time
      ultrasound. Twenty metastatic nodes and 40 reactive nodes were less than 10 mm in
      maximum transverse diameter. The vascular patterns of lymph nodes were classified
      into three categories: (1) hilar; (2) capsular; (3) hilar and capsular. The
      resistive index (RI) and pulsatility index (PI) were measured by spectral
      Doppler. RESULTS: Although metastatic nodes (RI, 0.81 +/- 0.11; PI, 1.89 +/-
      0.89) tended to have higher intranodal vascular resistance than reactive nodes
      (RI, 0.65 +/- 0.08; PI, 1.07 +/- 0.26), there was considerable overlap of the
      resistance parameters between benign and malignant nodes. Most of the metastatic
      nodes showed the presence of capsular vascularity (capsular, 16%; capsular and
      hilar, 78%), whereas the majority of the reactive nodes showed hilar vascularity
      (98%), and the difference was significant. CONCLUSION: The distribution of
      intranodal vascularity appears to be more useful than RI or PI in differentiating
      benign from malignant cervical lymphadenopathy. It is also easier to evaluate the
      distribution and the results are therefore readily applicable in routine clinical
      practice.

PMID- 11247697
TI  - Chest pain following oesophageal stenting for malignant dysphagia.
AB  - AIM: The palliative use of self-expanding metallic stents has been widely
      reported to relieve dysphagia in cases of oesophageal carcinoma. Little has been
      documented on the severity of chest pain following oesophageal stenting. The aim
      of this study was to investigate the association of pain with oesophageal
      stenting for malignant dysphagia. METHODS: Fifty-two patients with inoperable
      oesophageal carcinoma underwent stent placement between 1995-1999. Daily opioid
      analgesic requirements (mg of morphine equivalent doses) were monitored for 3
      days before and 7 days after stenting. The degree of palliation was expressed as
      a dysphagia score (0-3). Hospital stay, readmission days, stent complications and
      patient survival time were also recorded. RESULTS: Twenty-six patients (50%)
      required opioid analgesia for chest pain (median dose: 80 mg morphine/day) within
      48 h of the procedure compared to 11 (21.2%) patients before stenting (P =
      0.0041). A significant increase was evident in the analgesic consumption
      following stent deployment (P < 0.001). The dysphagia score improved by a median
      value of 1 (CI 0.25)P < 0.001, with a re-intervention rate of 11.5%. The median
      survival time was 40 days post stenting (range 1-120). CONCLUSION: A significant
      proportion of patients developed chest pain after oesophageal stenting, requiring
      high dose opioid analgesia. As the origin of the pain is still unknown, pre
      emptive analgesia may a play role in reducing stent-related morbidity and
      possibly in-hospital stay.

PMID- 11247698
TI  - Imaging of non-central nervous system primitive neuroectodermal tumours:
      diagnostic features and correlation with outcome.
AB  - AIM: To document the varied radiological features before, during, and after
      treatment of non-Central Nervous System Primitive Neuroectodermal Tumours
      (PNETs), which are rare tumours of childhood. MATERIALS AND METHODS: Thirty-three
      children with PNETs have been treated at our institution between 1990 and 1999.
      Full radiological and clinical follow-up was obtained in 29 (17 females, 12
      males). Imaging was retrospectively reviewed, with particular attention to
      Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). RESULTS: Age range
      at diagnosis was 0-16 years old (mean 4.4 years). There were five main sites of
      tumour: head and neck (n = 7), scapula/axilla (n = 2), chest (n = 11), abdomen (n
      = 3), and spinal/paraspinal (n = 6). Overall mortality was 62%. Tumours of the
      scapula or paraspinal region appear to show better survival than other sites. Of
      23 patients who had Tc99m-methylene diphosphonate (MDP) bone scans at diagnosis,
      four patients showed widespread distant metastases, seven showed focal increased
      uptake in an adjacent bone only, and 12 had normal examinations. CT was performed
      in 25 patients and MRI in 20, both at diagnosis and follow-up. Average size of
      tumours at presentation was 4.5 cm in the paraspinal, head and neck and scapular
      regions and 7.5 cm in the chest and abdomen. Tumours were typically of soft
      tissue density on CT with the larger (>5 cm) masses tending to be more
      heterogeneous in character. The lesions were slightly higher signal than muscle
      on T1-weighted (T1W) MRI and all masses were heterogeneous on T2W sequences.
      Calcification was uncommon (n = 6) and generally sparse. Tumours tended to
      displace adjacent soft tissue structures such as vessels and bronchi rather than
      invade or encase them. Tumours rarely crossed the midline. Local or bony invasion
      was seen in 12 patients at diagnosis. Metastases were identified in the lung (n =
      5), pleura (n = 2), brain (n = 4), bone (n = 4), lymph nodes (n = 2), liver (n =
      2), subcutaneous tissues (n = 2), kidney (n = 1) and peritoneum (n = 1).
      CONCLUSIONS: Imaging characteristics of non-CNS PNETs are described. Tumours tend
      to displace rather than encase adjacent structures; local invasion occurred in
      43%. Tumour calcification is uncommon. Poor prognostic features included the
      presence of distant metastases at diagnosis (all four patients with distant
      metastases at diagnosis died), but even patients without metastatic disease have
      a relatively poor prognosis.

PMID- 11247699
TI  - Lobular carcinoma in situ on core biopsy-what is the clinical significance?
AB  - AIM: To retrospectively review the surgical histological findings in all cases
      where lobular carcinoma in situ(LCIS) was identified on percutaneous core biopsy
      (CB) performed as part of the Cambridge and Huntingdon breast screening
      programme. MATERIALS AND METHODS: We retrospectively reviewed all the core
      biopsies performed in our department for screen detected abnormalities over a 5
      year period between 1 April 1994 and 31 March 1999. All patients where LCIS was
      identified on CB were reviewed. As the significance of LCIS on CB was unclear all
      went on to surgical excision. We reviewed the clinical and imaging findings,
      biopsy technique and subsequent surgical histology of each patient. RESULTS:
      During the study period 60 769 women were invited for screening, of whom 47 975
      attended (attendance rate = 79%). Of these, 2330 (4.9%) were recalled for
      assessment and 749 (1.6%) underwent CB. A malignant diagnosis was obtained in 311
      (42%), 211 invasive and 100 in situ lesions. LCIS was identified on CB in 13
      (2%). LCIS was the only lesion identified in seven cases. All seven cases
      subsequently underwent surgical excision. Surgical histology revealed a single
      case of LCIS and invasive lobular carcinoma. There were two cases of LCIS and
      DCIS one with a probable focus of invasive ductal carcinoma. In one case LCIS was
      identified in association with a radial scar. In three of the seven cases LCIS
      was the only abnormality on both CB and surgical biopsy. CONCLUSION: Our series
      shows that isolated LCIS on CB following mammographic screening is an infrequent
      finding, and it may be associated with either an invasive cancer or DCIS. It is
      therefore advisable that when LCIS is identified on CB, surgical excision of the
      mammographic abnormality should be performed. Decisions on management should be
      undertaken in a multidisciplinary setting taking into account clinical and
      imaging findings.

PMID- 11247700
TI  - Radionuclide bone scintigraphy in the detection of significant complications
      after total knee joint replacement.
AB  - AIM: Post-arthroplasty knee pain is common and clinically it can be difficult to
      identify those patients with complications requiring active treatment. The aim of
      this study was to determine the usefulness of(99)Tc(m)-MDP bone scintigraphy.
      METHOD: A retrospective study of all patients having a(99)Tc(m)-MDP bone
      scintigram for a painful knee arthroplasty between 1993 and 1999 was performed.
      Bone scintigrams were classified as normal or abnormal by a single observer. The
      results of these investigations were correlated with clinical outcome. RESULTS:
      Seventy-five patients with painful knee arthroplasties were referred for
      investigation. A total of 80 bone scintigrams were performed. The average patient
      age was 66.2 years (42 female and 33 male). The mean time period between surgery
      and onset of knee pain was 3 years. A final clinical diagnosis based on
      arthroscopy, open surgery, and extended clinical follow-up was available for all
      patients. Forty-three (53.8%) of the scintigrams were normal and 37 (46.3%)
      abnormal. Two patients with a normal bone scintigram has loose prostheses.
      Thirteen patients with an abnormal study had normal prostheses on follow-up and
      these tended to be patients scanned less than a year after surgery. The
      sensitivity, specificity, positive predictive value and negative predictive value
      of an unequivocally normal or abnormal bone scintigram was 92.3, 75.9, 64.9 and
      95.0%, respectively. The pattern of isotope uptake in the abnormal studies was
      not specific enough to reliably differentiate aseptic from septic loosening.
      CONCLUSION: Radionuclide bone scintigraphy is useful in the assessment of the
      painful knee arthroplasty. A negative bone scintigram is reassuring and makes
      loosening or infection unlikely.

PMID- 11247701
TI  - Transabdominal ultrasonography of the small bowel after oral administration of a
      non-absorbable anechoic solution: comparison with barium enteroclysis.
AB  - AIM: The aim of this study was to determine if oral administration of a non
      absorbable anechoic solution conveys any benefit during abdominal ultrasound
      (US), with special reference to its accuracy. MATERIALS AND METHODS: Fifty-three
      adult out-patients scheduled for small bowel barium enema (SBE) were included.
      The day before SBE all patients underwent abdominal US before and after oral
      administration of an isotonic non-absorbable electrolyte solution containing
      polyethylene glycol (PEG-ELS). Sensitivity and specificity were evaluated using
      SBE as a gold standard. RESULTS: After ingestion of PEG-ELS satisfactory
      distension of the intestinal lumen was obtained (11-25 mm) with sequential
      visualization of jejunoileal loops in 30.9 +/- 17.3 min. In 15 out of 53 cases
      both US and SBE showed bowel changes characteristic of Crohn's disease. In three
      out of 53 cases both US and SBE showed neoplasms. In one out of 53 cases US was
      negative, SBE positive for local nodularity and ulcerations typical of Crohn's
      disease. In one out of 53 cases US was negative, SBE positive for macronodularity
      consistent with coeliac disease. In five out of 53 cases US was negative, while
      SBE was positive for mininodularity expressive of lymphoid hyperplasia. In 28 out
      of 53 cases both examinations were negative. CONCLUSION: PEG-ELS administration
      allows a thorough US investigation of the small bowel, with fair sensitivity
      (72%) and excellent specificity (100%). False negative findings are mainly due to
      lymphoid hyperplasia, a feature of uncertain significance in adults.

PMID- 11247702
TI  - Detection of intraarticular bodies of the elbow with saline arthrosonography.
AB  - AIM: To assess whether ultrasound with intraarticular injection of saline
      increases the detection of intraarticular bodies of the elbow. SUBJECTS AND
      METHODS: Twelve patients (age range 21-42 years, mean 29 years; 8 male, 4 female)
      referred over a 2-year period with an equivocal history of elbow locking and
      plain radiographs had a joint injection of at least 12 ml of sterile saline
      during ultrasound examination. No patient had a joint effusion before injection.
      Surgical correlation was available in six patients. RESULTS: Ten patients had
      intraarticular bodies but these were demonstrated only after joint injection in
      six patients. Arthroscopy performed in six patients confirmed intraarticular
      bodies in five. Radiographs were falsely positive in one and falsely negative in
      seven patients. CONCLUSION: Joint injection improves the sonographic evaluation
      and conspicuity of small and radiographically occult intraarticular loose bodies
      in the clinically equivocal elbow. The procedure is simple, quick, well tolerated
      and reproducible.

PMID- 11247703
TI  - Dual phase helical CT versus portal venous phase CT for the detection of
      colorectal liver metastases: correlation with intra-operative sonography,
      surgical and pathological findings.
AB  - AIM: To assess whether dual phase helical computed tomography (DPCT) of the liver
      improves the detection of colorectal liver metastases compared with portal venous
      phase (PVP) imaging alone. MATERIALS AND METHODS: DPCT was performed in 33
      consecutive patients before laparotomy for resection of colorectal liver
      metastases. CT comprised 8-mm slice collimation with a pitch of 1 to 1.25;
      imaging was commenced 20-25 and 65-70 s after the start of injection of 150 ml of
      contrast medium at 5 ml/s to coincide with hepatic arterial phase (HAP) and PVP
      contrast enhancement, respectively. Four blinded observers independently reviewed
      the HAP, PVP and DPCT images recording the site and size of all lesions.
      Alternative-free response receiver operating characteristic (AFROC) methodology
      was used to analyse the results, which were correlated with surgery, intra
      operative ultrasound and histology. RESULTS: The mean observer sensitivities for
      malignant lesion detection were 75.3% for DPCT, 69.7% for PVP imaging and 66.7%
      for HAP imaging alone. There was a statistically significant improvement in
      malignant lesion detection using DPCT when compared with PVP imaging alone (P <
      0.05). The mean areas under the AFROC curves were 0.84 for DPCT and 0.82 for PVP
      (P < 0.03) imaging alone. CONCLUSION: The detection of colorectal liver
      metastases was marginally better with DPCT than with PVP imaging alone, but the
      discovery of additional lesions did not affect the management of any of the
      patients in this study.

PMID- 11247704
TI  - Percutaneous management of a choledochocutaneous fistula.

PMID- 11247705
TI  - An unusual case of ataxia.

PMID- 11247706
TI  - Carcinoid crisis provoked by mammographic compression of metastatic carcinoid
      tumour of the breast.

PMID- 11247707
TI  - Guide to development of practice guidelines.

PMID- 11247708
TI  - Search for primary infection by Pneumocystis carinii in a cohort of normal,
      healthy infants.
AB  - To determine whether Pneumocystis carinii is associated with clinical illness in
      the competent host, 107 normal, healthy infants were enrolled in a 2-year
      prospective cohort study in Chile. P. carinii was identified by specific stains
      and nested--deoxyribonucleic acid (DNA) amplification of the large subunit
      mitochondrial ribosomal ribonucleic acid gene of P. carinii f. sp. hominis, and
      seroconversion was assessed by enzyme-linked immunosorbent assay of serum samples
      drawn every 2 months. P. carinii DNA was identified in nasopharyngeal aspirates
      obtained during episodes of mild respiratory infection in 24 (32%) of 74 infants
      from whom specimens were available for testing. Three (12.5%) of those 24 infants
      versus 0 of 50 infants who tested negative for P. carinii had apnea episodes.
      Seroconversion developed in 67 (85%) of 79 infants who remained in the study by
      20 months of age and occurred in the absence of any symptoms of disease in 14
      (20.8%). The study indicates that P. carinii DNA can be frequently detected in
      healthy infants, and it raises the hypothesis that they may be an infectious
      reservoir of P. carinii in the community. Further investigation is needed to
      identify whether P. carinii causes overt respiratory disease in infants.

PMID- 11247709
TI  - Serial measurements of hematologic counts during the active phase of human
      granulocytic ehrlichiosis.
AB  - To describe the changes that occur in blood count parameters during the natural
      course of human granulocytic ehrlichiosis, we designed a retrospective cross
      sectional case study of 144 patients with human granulocytic ehrlichiosis and
      matched controls who had a different acute febrile illness. Patients from New
      York State and the upper Midwest were evaluated from June 1990 through December
      1998. Routine complete blood counts and manual differential leukocyte counts of
      peripheral blood were performed on blood samples that were collected during the
      active illness, and values were recorded until the day of treatment with an
      active antibiotic drug. Thrombocytopenia was observed more frequently than was
      leukopenia, and the risk of having ehrlichiosis varied inversely with the
      granulocyte count and the platelet count. Patients with ehrlichiosis displayed
      relative and absolute lymphopenia and had a significant increase in band
      neutrophil counts during the first week of illness. Knowledge of characteristic
      complete blood count patterns that occur during active ehrlichiosis may help
      clinicians to identify patients who should be evaluated specifically for
      ehrlichiosis and who should receive empiric antibiotic treatment with
      doxycycline.

PMID- 11247710
TI  - Adenovirus infections in adult recipients of blood and marrow transplants.
AB  - Adenoviruses are increasingly recognized pathogens that affect blood and marrow
      transplant (BMT) recipients. Experiences with 2889 adult BMT recipients were
      reviewed to study the incidence, clinical spectrum, risk factors for
      dissemination, response to therapy, and outcome of adenovirus infections. Eight
      five patients (3%) were diagnosed by means of culture (n=85) or culture and
      histopathological examination (n=6). Nine patients had asymptomatic viruria, and
      76 had symptomatic infections, which included upper respiratory tract infection
      (n=20), enteritis (n=18), hemorrhagic cystitis (n=10), pneumonia (n=15), and
      disseminated disease (n=13). The overall mortality rate was 26%. A higher
      mortality rate was observed among patients with pneumonia (73%) and disseminated
      disease (61%). Risk factors for dissemination included receipt of an allogeneic
      transplant, presence of graft-versus-host disease (GVHD), and receipt of
      concurrent immunosuppressive therapy. Intravenous ribavirin was not associated
      with an appreciable benefit among 12 patients who received this treatment. In
      conclusion, adenovirus infections are an important cause of morbidity and
      mortality in adult BMT recipients, particularly allogeneic transplant recipients
      with GVHD who are receiving immunosuppressive therapy. The need for an effective,
      nontoxic antiviral therapy is apparent.

PMID- 11247711
TI  - Poststernotomy mediastinitis due to Staphylococcus aureus: comparison of
      methicillin-resistant and methicillin-susceptible cases.
AB  - The objective of the study was to compare the outcome of poststernotomy
      mediastinitis (PSM) caused by methicillin-resistant and methicillin-susceptible
      Staphylococcus aureus (MRSA and MSSA, respectively). Hospital records of 41
      patients with S. aureus PSM who were all treated by closed drainage from 1 April
      1996 through 1 February 2000 were reviewed. PSM was caused by MRSA in 15 patients
      and by MSSA in 26. Follow-up (+/-SD) averaged 12.5+/-14.0 months per patient.
      Both groups had similar perioperative characteristics. Patients with MRSA PSM had
      a significantly lower actuarial survival rate than did patients with MSSA PSM
      (60.0%+/-12.6%, 52.5%+/-3.4%, and 26.3%+/-19.7% versus 84.6%+/-7.1%, 79.0%+/
      8.6%, and 79.0%+/-8.65 at 1 month, and at 1 and 3 years, respectively; values are
      +/- SD; P=.04). PSM-related death and treatment failure were significantly higher
      in the MRSA group than in the MSSA group (P=.03 and.02, respectively). Logistic
      regression analysis revealed that MRSA was the only independent risk factor for
      overall mortality. In conclusion, the clinical outcome of PSM caused by MRSA is
      poorer than that caused by MSSA.

PMID- 11247712
TI  - Treatment failure with the use of ciprofloxacin for gonorrhea correlates with the
      prevalence of fluoroquinolone-resistant Neisseria gonorrhoeae strains in
      Bangladesh.
AB  - Although ciprofloxacin is one of the recommended drugs of choice for the
      treatment of gonorrhea, in vitro resistance to this drug has been observed in
      surveillance studies and case reports from many parts of the world, including
      Bangladesh. However, to our knowledge, there have been no prospective studies of
      the correlation between in vitro response to the drug and treatment outcome.
      Therefore, a prospective study of 217 female sex workers in Dhaka, Bangladesh,
      was conducted to examine the correlation between the in vitro response of
      Neisseria gonorrhoeae and the outcome of ciprofloxacin treatment. Overall, 37.8%
      of the gonococcal isolates recovered from female sex workers were resistant to
      ciprofloxacin, and there was a good correlation between in vitro resistance and
      treatment failure. These findings suggest that in vitro resistance to
      ciprofloxacin is predictive of clinical treatment failure in patients with
      gonorrhea.

PMID- 11247714
TI  - Ticks and tickborne bacterial diseases in humans: an emerging infectious threat.
AB  - Ticks are currently considered to be second only to mosquitoes as vectors of
      human infectious diseases in the world. Each tick species has preferred
      environmental conditions and biotopes that determine the geographic distribution
      of the ticks and, consequently, the risk areas for tickborne diseases. This is
      particularly the case when ticks are vectors and reservoirs of the pathogens.
      Since the identification of Borrelia burgdorferi as the agent of Lyme disease in
      1982, 15 ixodid-borne bacterial pathogens have been described throughout the
      world, including 8 rickettsiae, 3 ehrlichiae, and 4 species of the Borrelia
      burgdorferi complex. This article reviews and illustrate various aspects of the
      biology of ticks and the tickborne bacterial diseases (rickettsioses,
      ehrlichioses, Lyme disease, relapsing fever borrelioses, tularemia, Q fever),
      particularly those regarded as emerging diseases. Methods are described for the
      detection and isolation of bacteria from ticks and advice is given on how tick
      bites may be prevented and how clinicians should deal with patients who have been
      bitten by ticks.

PMID- 11247713
TI  - Emergence of Salmonella enteritidis phage type 4 in the Caribbean: case-control
      study in Trinidad and Tobago, West Indies.
AB  - A prospective case-control study involving 46 case patients and 92 age- and
      neighborhood-matched control subjects was conducted in Trinidad and Tobago (T&T)
      between March 1998 and May 1999 to determine the etiology, sources, and risk
      factors for Salmonella enteritidis (SE) infection. SE infection in T&T was found
      to be associated with the consumption of shell eggs, and in particular raw or
      undercooked eggs. SE isolates from 30 (88%) of 34 patients and from 9 implicated
      egg or egg-containing food samples were phage type 4. Homemade eggnog and ice
      cream, cake batter, and egg-containing beverages were the main raw egg-containing
      foods, reflecting the cultural practices of the people of T&T. Public health
      education on the risks of eating raw or undercooked eggs, thorough cooking of all
      egg dishes, and refrigeration of shell eggs and egg dishes; studies tracing
      infected eggs to their sources; and testing of flocks of layer chickens for SE
      are needed to reduce the incidence of this infection.

PMID- 11247715
TI  - Update on leprosy in immigrants in the United States: status in the year 2000.
AB  - The World Health Organization established a goal in 1991 of "elimination of
      leprosy as a public health problem by the year 2000." Although prevalence rates
      of leprosy have decreased in many geographic areas, it is clear that in some
      countries where leprosy is endemic, such as Brazil and India, this goal will not
      be reached. Leprosy is rare in the United States, but 85% of detected cases are
      in immigrants in whom the disease may mimic many common dermatologic and
      neurological entities, leading to delay of diagnosis. The statuses of polymerase
      chain reaction analysis, serological testing, and vaccines are reviewed.
      Effective multidrug therapy and prevention of permanent damage to nerves by early
      recognition and treatment will help prevent residual disabilities. This update
      reviews what is known about the pathophysiology and treatment of leprosy.
      Increased awareness will lead to earlier recognition, diagnosis, and treatment.

PMID- 11247716
TI  - Chronic fatigue syndrome and fibromyalgia resources on the world wide web: a
      descriptive journey.
AB  - A wealth of information on chronic fatigue syndrome (CFS) and fibromyalgia is
      available on the World Wide Web for health care providers and patients. These
      illnesses have overlapping features, and their etiologies remain unknown.
      Multiple Web sites were reviewed, and selected sites providing useful information
      were identified. Sites were classified according to their content and target
      audience and were judged according to suggested standards of Internet publishing.
      Fifty-eight sites were classified into groups as follows: comprehensive and
      research Web sites for CFS and fibromyalgia, meetings, clinical trials,
      literature search services, bibliographies, journal, and CFS and fibromyalgia Web
      sites for the patient.

PMID- 11247717
TI  - State-of-the-art treatment of chronic venous disease.
AB  - The article summarizes the epidemiology, classification and differential
      diagnosis of venous disease and its complications. Theories of venous ulceration
      and diagnostic and treatment modalities are reviewed.

PMID- 11247718
TI  - Clinical presentation and risk behaviors of patients with acquired
      immunodeficiency syndrome in Thailand, 1994--1998: regional variation and
      temporal trends.
AB  - From 1994 through 1998, the clinical and demographic features and risk behaviors
      of 101,945 adolescent and adult patients with acquired immunodeficiency syndrome
      (AIDS) were reported to the Ministry of Public Health in Thailand. The number of
      reported cases of AIDS infection increased from 12,005 in 1994 to 24,722 in 1997.
      Nearly 40% of the cases were reported from the northern provinces, which
      contained only approximately 20% of the adult population. About 80% of cases were
      among male patients, and 87% had been acquired via sexual contact. Tuberculosis
      was the most commonly reported opportunistic infection, occurring in 28.9% of
      patients; it was more commonly reported among injection drug abusers, especially
      in Bangkok. Pneumocystis carinii pneumonia and cryptococcal meningitis each
      occurred in nearly 20% of patients and were more frequently reported in patients
      with risk factors related to sex than in injection drug abusers. Penicillium
      marneffei infections were reported in 6.8% of patients from the northern
      provinces but less frequently elsewhere. These data suggest that AIDS is common
      in Thailand, and human immunodeficiency virus-infected persons should be given
      prophylaxis for tuberculosis, fungal infections, and P. carinii pneumonia.

PMID- 11247719
TI  - Evaluation of chronic hepatitis B virus (HBV) infection in coinfected patients
      receiving lamivudine as a component of anti-human immunodeficiency virus
      regimens.
AB  - The effect of lamivudine on chronic coinfection with hepatitis B virus (HBV) in
      human immunodeficiency virus (HIV)--infected patients was studied prospectively.
      Nineteen patients with HIV infection, who were receiving an anti-HIV regimen
      containing lamivudine (150 mg twice daily), and who had replicative chronic HBV
      infection, were followed for a median of 14 months. Twelve patients' regimens
      contained protease inhibitors. Serum HBV DNA became undetectable, by means of
      molecular hybridization, in 14. Seroconversion of hepatitis B e antigen to
      antibody occurred in 6 of 17 patients, and seroconversion of hepatitis B surface
      antigen to antibody occurred in 1 of 19. The median serum alanine
      aminotransferase concentration had decreased by the time of the final evaluation.
      The median CD4 cell count increased and plasma HIV RNA was undetectable in 10 of
      19 patients. Five patients had recurrence of detectable serum HBV DNA despite
      good compliance with treatment, and 2 mutations related to the resistance of HBV
      were detected. These patients had a significantly longer duration of treatment
      (21 versus 13 months; P<.05). In conclusion, resistant strains of HBV emerge at
      high detectable levels while patients receive anti-HIV regimens containing
      lamivudine.

PMID- 11247720
TI  - Penicillin-resistant Streptococcus pneumoniae endocarditis: a case report and
      review.
AB  - Streptococcus pneumoniae has been a rare cause of endocarditis in the
      postantibiotic era. The emergence of antibiotic-resistant Pneumococcus species
      has been accompanied by isolated reports of penicillin-resistant S. pneumoniae
      (PRSP) endocarditis. We report a case of bivalvular PRSP endocarditis that was
      treated with vancomycin and trovafloxacin, and we review the literature on this
      topic.

PMID- 11247721
TI  - Significance of Clostridium tertium bacteremia in neutropenic and nonneutropenic
      patients: review of 32 cases.
AB  - In the nonneutropenic host, bacteremia due to Clostridium tertium is rare and of
      unclear significance. We describe a patient in whom presentation with Clostridium
      tertium bacteremia was the harbinger of Crohn's disease. In order to understand
      the significance of C. tertium bacteremia in neutropenic and nonneutropenic
      hosts, we review all 32 cases of C. tertium bacteremia that occurred at Duke
      University Medical Center from 1992 to 1999.

PMID- 11247722
TI  - Epidemic typhus meningitis in the southwestern United States.
AB  - A patient residing in New Mexico had murine typhus diagnosed. A novel molecular
      assay was performed at the Centers for Disease Control and Prevention, and
      Rickettsia prowazekii, the agent of epidemic typhus, was found, rather than R.
      typhi. To our knowledge, this is the first reported case of epidemic typhus
      confirmed by means of polymerase chain reaction--based testing of cerebrospinal
      fluid, and it introduces a novel assay for the molecular diagnosis of both
      epidemic and murine typhus.

PMID- 11247723
TI  - Acute cytomegalovirus infection complicated by vascular thrombosis: a case
      report.
AB  - We present a case report of a previously healthy adult with cytomegalovirus
      infection that was complicated by extensive mesenteric arterial and venous
      thrombosis. To our knowledge, this is the first reported case of this syndrome in
      an immunocompetent individual who had no predisposing risk factors for
      thrombosis, and it demonstrates the propensity for cytomegalovirus to be involved
      in vascular disease.

PMID- 11247724
TI  - Possible misidentification of Haemophilus aphrophilus as Pasteurella gallinarum.

PMID- 11247725
TI  - Long-term high-dose acyclovir and AIDS-related non-Hodgkins lymphoma.

PMID- 11247727
TI  - Comparison of nephrotoxicity of amphotericin B products.

PMID- 11247728
TI  - Unmasking mask aversion.

PMID- 11247729
TI  - Prevalence of infection with human immunodeficiency virus in East Timor.

PMID- 11247730
TI  - Late prosthetic valve endocarditis caused by Staphylococcus hemolyticus.
AB  - We describe a case of late PVE in a 78-year-old man that was caused by
      Stapylococcus hemolyticus and occurred 5 years after aortic valve replacement.
      This is the first reported case of PVE due to this organism.

PMID- 11247731
TI  - Pediatric septic bursitis: case report of retrocalcaneal infection and review of
      the literature.
AB  - Septic bursitis in children is rarely discussed in the medical literature. This
      review summarizes the clinical manifestations and management of 10 cases of
      septic bursitis involving patients aged <16 years. In every case in this series,
      acute trauma was the predisposing condition. Group A streptococci were frequently
      isolated from the infected bursa. Septic bursitis, an underappreciated infection
      in children, should be considered in the differential diagnosis of common
      childhood conditions.

PMID- 11247732
TI  - Adult Still's disease associated with Mycoplasma pneumoniae infection.
AB  - Adult Still's disease (ASD) is a systemic inflammatory disorder of unknown
      origin. Several reports have suggested a triggering infection in ASD. We describe
      a case of ASD associated with acute Mycoplasma pneumoniae infection. The close
      temporal relationship between ASD and acute infection strongly suggests that M.
      pneumoniae triggered ASD. We suggest that M. pneumoniae should be added to the
      list of infectious agents that may play a role in its etiology.

PMID- 11247733
TI  - Successful treatment of an infant with Chromobacterium violaceum sepsis.
AB  - Chromobacterium violaceum sepsis, a rarely reported phenomenon, has a high
      mortality rate. We report a unique case of C. violaceum sepsis in an infant. A 4
      month-old girl presented to our institution with fever, pustular skin lesions,
      and distended abdomen, as well as diminished activity and mental status.
      Radiological investigation revealed brain, lung, and hepatic abscesses. The
      infant was successfully treated with trimethoprim-sulfamethoxazole and
      ciprofloxacin.

PMID- 11247734
TI  - Captivity diets alter egg yolk lipids of a bird of prey (the American kestrel)
      and of a galliforme (the red-legged partridge).
AB  - The salient feature of the fatty acid profile of kestrel eggs collected in the
      wild was the very high proportion of arachidonic acid (15.2%+/-0.7% of fatty acid
      mass, n=5) in the phospholipid fraction of the yolk. Kestrels in captivity fed on
      day-old chickens produced eggs that differed from those of the wild birds in a
      number of compositional features: the proportion of linoleic acid was increased
      in all the lipid fractions; the proportion of arachidonic acid was increased in
      yolk phospholipid and cholesteryl ester; the proportion of alpha-linolenic acid
      was decreased in all lipid classes, and that of docosahexaenoic acid was
      decreased in phospholipid and cholesteryl ester. Partridge eggs from the wild
      contained linoleic acid as the main polyunsaturate of all the yolk lipid
      fractions. Captive partridges maintained on a formulated diet very rich in
      linoleic acid produced eggs with increased levels of linoleic, arachidonic, and n
      6 docosapentaenoic acids in the phospholipid fraction; reduced proportions of
      alpha-linolenic acid were observed in all lipid classes, and the proportion of
      docosahexaenoic acid was markedly reduced in the phospholipid fraction. Thus,
      captive breeding of both the kestrel and the partridge increases the n-6/n-3
      polyunsaturate ratio of the yolk lipids.

PMID- 11247735
TI  - Metabolic heating and the prediction of sex ratios for green turtles (Chelonia
      mydas).
AB  - We compared incubation temperatures in nests (n=32) of the green turtle (Chelonia
      mydas) on Ascension Island in relation to sand temperatures of control sites at
      nest depth. Intrabeach thermal variation was low, whereas interbeach thermal
      variation was high in both control and nest sites. A marked rise in temperature
      was recorded in nests from 30% to 40% of the way through the incubation period
      and attributed to metabolic heating. Over the entire incubation period, metabolic
      heating accounted for a mean rise in temperature of between 0.07 degrees and 2.86
      degrees C within nests. During the middle third of incubation, when sex is
      thought to be determined, this rise in temperature ranged between 0.07 degrees
      and 2.61 degrees C. Metabolic heating was related to both the number of eggs laid
      and the total number of hatchlings/embryos produced in a clutch. For 32 clutches
      in which temperature was recorded, we estimate that metabolic heating accounted
      for a rise of up to 30% in the proportion of females produced within different
      clutches. Previous studies have dismissed any effect of metabolic heating on the
      sex ratio of marine turtle hatchlings. Our results imply that metabolic heating
      needs to be considered when estimating green turtle hatchling sex ratios.

PMID- 11247736
TI  - Regulation of drinking rate in euryhaline tilapia larvae (Oreochromis
      mossambicus) during salinity challenges.
AB  - Euryhaline tilapia larvae are capable of adapting to environmental salinity
      changes even when transferred from freshwater (FW) to seawater (SW) or vice
      versa. In this study, the water balance of developing tilapia larvae (Oreochromis
      mossambicus) adapted to FW or SW was compared, and the short-term regulation of
      drinking rate of the larvae during salinity adaptation was also examined.
      Following development, wet weight and water content of both SW- and FW-adapted
      larvae increased gradually, while the dry weight of both group larvae showed a
      slow but significant decline. On the other hand, the drinking rate of SW-adapted
      larvae was four- to ninefold higher than that of FW-adapted larvae from day 2 to
      day 5 after hatching. During acute salinity challenges, tilapia larvae reacted
      profoundly in drinking rate, that is, increased or decreased drinking rate within
      several hours while facing hypertonic or hypotonic challenges, to maintain their
      constancy of body fluid. This rapid regulation in water balance upon salinity
      challenges may be critical for the development and survival of developing larvae.

PMID- 11247737
TI  - Body oxygen stores, aerobic dive limits, and the diving abilities of juvenile and
      adult muskrats (Ondatra zibethicus).
AB  - Intraspecific variability in body oxygen reserves, muscle buffering capacity,
      diving metabolic rate, and diving behavior were examined in recently captured
      juvenile and adult muskrats. Allometric scaling exponents for lung (b=1.04),
      blood (b=0.91), and total body oxygen storage capacity (b=1.09) did not differ
      from unity. The concentration of skeletal muscle myoglobin scaled positively with
      mass in 254-600-g juveniles (b=1.63) but was mass-independent in larger
      individuals. Scaling exponents for diving metabolic rate and calculated aerobic
      dive limit (ADL) were 0.74 and 0.37, respectively. Contrary to allometric
      predictions, we found no evidence that the diving abilities of muskrats increased
      with age or body size. Juveniles aged 1-2 mo exhibited similar dive times but
      dove more frequently than summer-caught adults. Average and cumulative dive times
      and dive&rcolon;surface ratios were highest for fall- and winter-caught muskrats.
      Total body oxygen reserves were greatest in winter, mainly due to an increase in
      blood oxygen storage capacity. The buffering capacity of the hind limb swimming
      muscles also was highest in winter-caught animals. Several behavioral indicators
      of dive performance, including average and maximum duration of voluntary dives,
      varied positively with blood hemoglobin and muscle myoglobin concentration of
      muskrats. However, none of the behavioral measures were strongly correlated with
      the total body oxygen reserves or ADLs derived for these same individuals.

PMID- 11247738
TI  - Field cost of activity in the kit fox, Vulpes macrotis.
AB  - Field metabolic rates and daily movement distances were measured in 26 individual
      kit foxes (Vulpes macrotis) over a 29-mo period in the southern Mojave Desert of
      California. Kit foxes traveled long distances (up to 32 km d(-1)), with males
      usually traveling farther than females. Daily movement distances were affected by
      season, since males traveled the greatest distances in spring and females
      traveled farthest in summer. Individual foxes tracked multiple times demonstrated
      repeatability of daily movement distance between nights, between summer and
      winter, and between consecutive winters. The field cost of activity per unit
      distance was estimated as 15.6 kJ km(-1) from the partial regression coefficient
      of a multiple linear regression model, a value not significantly different from
      the incremental cost of locomotion derived from laboratory measurements. The
      field cost of activity was not affected by season, despite the expectation of
      higher costs of activity in the winter with increased thermoregulatory
      expenditure. The large daily movement distances resulted in significant activity
      energy expenditure (11%-33% of field metabolic rate), with a mean of 21% of field
      metabolic rate expended in activity during nonreproductive seasons.

PMID- 11247739
TI  - Tissue-specific expression and cold-induced mRNA levels of uncoupling proteins in
      the Djungarian hamster.
AB  - The uncoupling protein 1 (UCP1), a mitochondrial transmembrane protein, is
      responsible for adaptive thermogenesis in brown adipose tissue (BAT). Two UCP1
      homologues, UCP2 and UCP3, were recently discovered, but it is controversial
      whether they also play a role in energy homeostasis. Djungarian hamster UCPs were
      found to exhibit high similarity with homologues known in other species. UCP1
      mRNA was restricted to BAT, UCP2 mRNA was expressed in multiple tissues, and UCP3
      mRNA was detected mainly in BAT and skeletal muscles. We examined the cold
      induced regulation of hamster UCP mRNA levels and tested their correlation with
      serum free fatty acid (FFA) concentrations. In BAT UCP1, UCP2, and UCP3
      expression was upregulated in the cold, but the increase and time course of
      increase differed. In skeletal muscle, UCP2 and UCP3 mRNA levels were not
      altered. Cold-induced changes of serum FFA levels correlated with the stimulation
      of UCP1 mRNA in BAT but not with UCP2 and UCP3.

PMID- 11247740
TI  - Early nutrition causes persistent effects on pheasant morphology.
AB  - Differences in growth conditions during early ontogeny have been suggested to
      cause permanent effects on the morphology and quality of birds. Yearly variation
      in growth conditions could thus result in morphological and quality differences
      between cohorts. In this study, we investigated the effect of small differences
      in the dietary protein content of captive ring-necked pheasants (Phasianus
      colchicus) during their first 8 wk posthatching. An experimental increase of the
      proportion of dietary protein during the first 3 wk of life accelerated growth,
      whereas a similar manipulation during the following 5 wk had only a limited
      effect. Compensatory growth during the postexperimental period equalized the size
      of chicks from different experimental treatments. However, a difference in tarsus
      length resulting from experimental treatment during the first 3 wk remained into
      adulthood. Furthermore, the protein content of the diet during the first 3 wk had
      an effect on the degree of fluctuating asymmetry in tarsus length, suggesting
      persistent effects on the quality of birds. The results of this study may explain
      size differences between cohorts that exist in pheasants and may also provide a
      link between the use of pesticides in agriculture and population effects on
      pheasants.

PMID- 11247742
TI  - The loach Misgurnus anguillicaudatus reduces amino acid catabolism and
      accumulates alanine and glutamine during aerial exposure.
AB  - The loach Misgurnus anguillicaudatus inhabits rice fields in Southern China. It
      encounters drought during summer and ammonia loading during agricultural
      fertilization. In the laboratory, aerial exposure led to decreases in its ammonia
      and urea excretion. Ammonia accumulated to very high levels in the muscle and
      liver. Urea synthesis through the ornithine-urea cycle was not involved in
      ammonia detoxification in M. anguillicaudatus. However, M. anguillicaudatus was
      capable of partial amino acid catabolism leading to the accumulation of alanine
      in the first 24 h of aerial exposure. This was apparently coupled to a possible
      decrease in protein/amino acid catabolism. These are not detoxification
      mechanisms but mechanisms that avoid internal fouling by ammonia. Misgurnus
      anguillicaudatus was also capable of detoxifying internally produced ammonia in
      part to glutamine, which appears to be an important adaptation after 24 h of
      aerial exposure. However, unlike the case of the marble goby (Oxyeleotris
      marmoratus), there was no alteration to the kinetic properties of the hepatic
      glutamine synthetase. During dry seasons, M. anguillicaudatus moves actively on
      land until it encounters soft mud in which it can bury itself through several
      strong wriggling actions of the body. Hence, it is possible that M.
      anguillicaudatus uses partial amino acid catabolism to fuel its short period of
      activities on land and switches to the formation of glutamine to detoxify
      internally produced ammonia when it remains relatively inactive in the mud.

PMID- 11247743
TI  - Thermoregulation and the energetic significance of clustering behavior in the
      white-backed mousebird (Colius colius).
AB  - Thermoregulation and the energetic significance of clustering behavior were
      assessed in the white-backed mousebird Colius colius. Basal metabolic rate was
      40% below the predicted allometric values. Rest-phase body temperature (T(b)) was
      highly labile and as low as 26 degrees C. Rest-phase T(b) was not regulated with
      respect to a constant set point temperature, as occurs typically in endotherms.
      Rather, we observed periods of linear decreases in rest-phase T(b) at a rate
      dependent on ambient temperature (T(a)) and the number of individuals in a
      cluster. The apparent inability of individual mousebirds to maintain rest-phase
      homeothermy suggests that clustering behavior is obligatory in the defense of a
      rest-phase set point T(b). The low rest-phase body temperatures exhibited by
      single C. colius hence appear to represent a normothermic state rather than
      typical avian facultative hypothermia. The birds were able to make significant
      energy savings by means of clustering behavior. These energy savings were
      dependent on T(a) and the number of birds in the cluster. At a T(a) of 15 degrees
      C, the mean energy expenditure of each bird in a cluster of six was 50% of that
      of a single bird. The metabolic traits of C. colius are likely be adaptive in the
      arid habitats that this species inhabits.

PMID- 11247741
TI  - Effects of helium/oxygen and temperature on aerobic metabolism in the marsupial
      sugar glider, Petaurus breviceps.
AB  - Helox (79% helium and 21% oxygen) has often been used for thermobiological
      studies, primarily because helium is thought to be metabolically inert and to
      produce no adverse effects other than increasing heat loss. However, these
      assumptions have been questioned. As basal metabolic rate (BMR) represents
      maintenance energy requirements for vital body functions, potential physiological
      effects of helox should be reflected in changes of BMR. In this study, sugar
      gliders were subjected to both air and helox atmospheres over a wide range of
      T(a)'s, including the thermoneutral zone (TNZ), to determine (1) whether helox
      has any influence other than on heat loss and (2) the maximum heat production
      (HP(max)) and thermal limits of this species. Although thermal conductance in the
      TNZ increased in helox, BMR was similar in air and helox (0.55+/-0.07 and 0.57+/
      0.06 mL g(-1) h(-1), respectively). The TNZ in helox, however, was shifted
      upwards by about 3 degrees C. Below the TNZ, sugar gliders were able to withstand
      an effective temperature of -24.7+/-7.3 degrees C with an HP(max) of 3.14+/-0.36
      mL g(-1) h(-1). The low effective temperature tolerated by sugar gliders shows
      that they are competent thermoregulators despite their apparent lack of
      functional brown fat. Similarities of BMRs in air and helox suggest that the
      effect of helox is restricted to an increase of heat loss, and, consequently,
      helox represents a useful tool for thermal physiologists. Moreover, the lack of
      increase of BMR in helox despite an increase in thermal conductance of sugar
      gliders suggests that BMR is not a function of body surface.

PMID- 11247744
TI  - Catabolic capacity of the muscles of shorebird chicks: maturation of function in
      relation to body size.
AB  - Newly hatched precocial chicks of arctic shorebirds are able to walk and regulate
      their body temperatures to a limited extent. Yet, they must also grow rapidly to
      achieve independence before the end of the short arctic growing season. A rapid
      growth rate may conflict with development of mature function, and because of the
      allometric scaling of thermal relationships, this trade-off might be resolved
      differently in large and small species. We assessed growth (mass) and functional
      maturity (catabolic enzyme activity) in leg and pectoral muscles of chicks aged 1
      16 d and adults of two scolopacid shorebirds, the smaller dunlin (Calidris
      alpina: neonate mass 8 g, adult mass 50 g) and larger whimbrel (Numenius
      phaeopus; neonate mass 34 g, adult mass 380 g). Enzyme activity indicates maximum
      catabolic capacity, which is one aspect of the development of functional maturity
      of muscle. The growth rate-maturity hypothesis predicts that the development of
      catabolic capacity should be delayed in faster-growing muscle masses. Leg muscles
      of both species were a larger proportion of adult size at hatching and grew
      faster than pectoral muscles. Pectoral muscles grew more rapidly in the dunlin
      than in the whimbrel, whereas leg muscles grew more rapidly in the whimbrel. In
      both species and in both leg and pectoral muscles, enzyme activities generally
      increased with age, suggesting increasing functional maturity. Levels of citrate
      synthase activity were similar to those reported for other species, but l-3
      hydroxyacyl-CoA-dehydrogenase and pyruvate kinase (PK) activities were
      comparatively high. Catabolic capacities of leg muscles were initially high
      compared to those of pectoral muscles, but with the exception of glycolytic (PK)
      capacities, these subsequently increased only modestly or even decreased as
      chicks grew. The earlier functional maturity of the more rapidly growing leg
      muscles, as well as the generally higher functional maturity in muscles of the
      more rapidly growing dunlin chicks, contradicts the growth rate-maturity function
      trade-off and suggests that birds have considerable latitude to modify this
      relationship. Whimbrel chicks, apparently, can rely on allometric scaling of
      power requirements for locomotion and the thermal inertia of their larger mass to
      reduce demands on their muscles, whereas dunlin chicks require muscles with
      higher metabolic capacity from an earlier age. Thus, larger and smaller species
      may adopt different strategies of growth and tissue maturation.

PMID- 11247745
TI  - Rapid metabolic recovery following vigorous exercise in burrow-dwelling larval
      sea lampreys (Petromyzon marinus).
AB  - Although the majority of the sea lamprey's (Petromyzon marinus) life cycle is
      spent as a burrow-dwelling larva, or ammocoete, surprisingly little is known
      about intermediary metabolism in this stage of the lamprey's life history. In
      this study, larval sea lampreys (ammocoetes) were vigorously exercised for 5 min,
      and their patterns of metabolic fuel depletion and replenishment and oxygen
      consumption, along with measurements of net whole-body acid and ion movements,
      were followed during a 4-24-h postexercise recovery period. Exercise led to
      initial five- to sixfold increases in postexercise oxygen consumption, which
      remained significantly elevated by 1.5-2.0 times for the next 3 h. Exercise also
      led to initial 55% drops in whole-body phosphocreatine, which was restored by 0.5
      h, but no significant changes in whole-body adenosine triphosphate were observed.
      Whole-body glycogen concentrations dropped by 70% immediately following exercise
      and were accompanied by a simultaneous ninefold increase in lactate. Glycogen and
      lactate were quickly restored to resting levels after 0.5 and 2.0 h,
      respectively. The presence of an associated metabolic acidosis was supported by
      very high rates of metabolic acid excretion, which approached 1,000 nmol g(-1)
      during the first 2 h of postexercise recovery. Exercise-induced ion imbalances
      were also rapidly alleviated, as initially high rates of net Na(+) and Cl(-) loss
      (-1,200 nmol g(-1) h(-1) and -1,800 nmol g(-1) h(-1), respectively) were
      corrected within 1-2 h. Although larval sea lampreys spend most of their time
      burrowed, they are adept at performing and recovering from vigorous anaerobic
      exercise. Such attributes could be important when these animals are vigorously
      swimming or burrowing as they evade predators or forage.

PMID- 11247746
TI  - Enzyme activities support the use of liver lipid-derived ketone bodies as aerobic
      fuels in muscle tissues of active sharks.
AB  - Few data exist to test the hypothesis that elasmobranchs utilize ketone bodies
      rather than fatty acids for aerobic metabolism in muscle, especially in
      continuously swimming, pelagic sharks, which are expected to be more reliant on
      lipid fuel stores during periods between feeding bouts and due to their high
      aerobic metabolic rates. Therefore, to provide support for this hypothesis,
      biochemical indices of lipid metabolism were measured in the slow-twitch,
      oxidative (red) myotomal muscle, heart, and liver of several active shark
      species, including the endothermic shortfin mako, Isurus oxyrinchus. Tissues were
      assayed spectrophotometrically for indicator enzymes of fatty acid oxidation (3
      hydroxy-o-acyl-CoA dehydrogenase), ketone-body catabolism (3-oxoacid-CoA
      transferase), and ketogenesis (hydroxy-methylglutaryl-CoA synthase). Red muscle
      and heart had high capacities for ketone utilization, low capacities for fatty
      acid oxidation, and undetectable levels of ketogenic enzymes. Liver demonstrated
      undetectable activities of ketone catabolic enzymes but high capacities for fatty
      acid oxidation and ketogenesis. Serum concentrations of the ketone beta
      hydroxybutyrate varied interspecifically (means of 0.128-0.978 micromol mL(-1))
      but were higher than levels previously reported for teleosts. These results are
      consistent with the hypothesis that aerobic metabolism in muscle tissue of active
      sharks utilizes ketone bodies, and not fatty acids, derived from liver lipid
      stores.

PMID- 11247747
TI  - Torpor and digestion in food-storing hibernators.
AB  - Many species of hibernating mammals rely on hoarded food rather than body fat to
      support winter energy requirements. Here, we evaluate whether the associated
      ingestive and digestive requirements reduce the benefits that food-storing
      hibernators can accrue from torpor. Using a simple model, we predict (1) that
      digestive efficiency could either increase or decrease with increased use of
      torpor, depending on the Q(10) of digestion relative to the Q(10) of whole-animal
      metabolism and (2) that increased torpor will result in a linear decrease in
      energy consumption but an exponential increase in euthermic intake requirements.
      In 16 captive eastern chipmunks (Tamias striatus), the proportion of time that
      different individuals spent in torpor was highly variable (29.8%+/-5.9%; 0.0%
      86.3%), positively correlated with dry matter digestibility (r2=0.53, P=0.02) and
      negatively correlated with energy consumption (r2=0.72, P=0.002). Thus, by both
      increasing conversion efficiency and reducing energy requirements, torpor appears
      to provide a double benefit for energy conservation by food-storing hibernators.
      Despite this, a comparative analysis shows that the euthermic intervals of food
      storing rodents are four times as long and torpor intervals are half as long as
      that of fat-storing rodents. Given that required euthermic intake rates are
      expected to increase exponentially at high levels of torpor, the reduced torpor
      expression of food-storing species may result from constraints on their ability
      to load enough food into the gut when euthermic to cover the energy requirements
      of the subsequent torpor cycle.

PMID- 11247748
TI  - Genetic and diurnal variation in the juvenile hormone titer in a wing-polymorphic
      cricket: implications for the evolution of life histories and dispersal.
AB  - The wing-polymorphic cricket, Gryllus firmus, contains (1) a flight-capable morph
      (LW(f)) with long wings and functional flight muscles, (2) a flightless morph
      with reduced wings and underdeveloped flight muscles (SW), and (3) a flightless
      morph with histolyzed flight muscles but with fully developed wings (LW(h)). The
      LW(f) morph differed genetically from the SW morph and phenotypically from the
      LW(h) morph in the size of flight muscles, ovarian growth during the first week
      of adulthood, and the hemolymph titer of juvenile hormone (JH). This is the first
      study to document that phenotypes that differ genetically in morphological
      aspects of dispersal capability and in ovarian growth also differ genetically in
      the titer of a hormone that potentially regulates those traits. The JH titer rose
      9-100-fold during the photophase in the flight-capable LW(f) morph but did not
      change significantly during this time in either flightless morph. Prolonged
      elevation of the in vivo JH titer in flight-capable females, by topical
      application of a hormone analogue, caused a substantial increase in ovarian
      growth and histolysis of flight muscles. The short-term, diurnal rise in the JH
      titer in the dispersing morph may be a mechanism that allows JH to positively
      regulate nocturnal flight behavior, while not causing maladaptive histolysis of
      flight muscles and ovarian growth. This is the first demonstration of naturally
      occurring, genetically based variation for diurnal change in a hormone titer in
      any organism.

PMID- 11247749
TI  - Intermittent feeding in a migratory omnivore: digestion and body composition of
      American black duck during autumn.
AB  - Birds fast intermittently during weather disturbances and migration. We tested
      responses of black duck to lost feeding days during autumn mass gain. Nine adult
      males were fed a pelleted diet (1.5% fat, 15.8% protein, and 18.3% neutral
      detergent fiber) and caged indoors during September and October (12 h light; 17
      degrees -24 degrees C) to measure balances over 14 d when fed ad lib. each day
      and fasted intermittently for 2 d wk(-1) (short fast) or 4 d wk(-1) (long fast).
      Body mass (1,081 g), body water content, and metabolizable intakes of energy and
      protein were maintained as daily intakes of dry matter increased to 1.65 (short
      fast) and 2.35 (long fast) times the unfasted level. Intermittent feeding reduced
      metabolizability of dry matter, energy, protein, and acid detergent fiber.
      Concentrations of Mn provided similar estimates of metabolizability to direct
      measures in unfasted birds but underestimated measures of birds on long fasts.
      Fasting regimes continued outdoors for 9 wk when temperatures declined to -9
      degrees C. Birds on short fasts were heavier (1,373 vs. 1,241 g) and fatter (159
      vs. 58 g) than those on long fasts, while body water (894 g) and protein (316 g)
      were similar between groups after 5 wk. Birds on long fasts subsequently gained
      mass when fed daily, but those on short fasts lost mass when fed each day.
      Omnivorous waterfowl combine ingestive and digestive flexibility with plasticity
      of body lipid to contend with uncertain food availability.

PMID- 11247750
TI  - Integrins and mechanotransduction of the vascular myogenic response.
AB  - This review summarizes what is currently known about the role of integrins in the
      vascular myogenic response. The myogenic response is the rapid and maintained
      constriction of a blood vessel in response to pressure elevation. A role for
      integrins in this process has been suggested because these molecules form an
      important mechanical link between the extracellular matrix and the vascular
      smooth muscle cytoskeleton. We briefly summarize evidence for a general role of
      integrins in mechanotransduction. We then describe the integrin subunit
      combinations known to exist in smooth muscle and the vascular wall matrix
      proteins that may interact with these integrins. We then discuss the effects of
      integrin-specific peptides and antibodies on vascular tone and on calcium entry
      mechanisms in vascular smooth muscle. Because integrin function is linked to the
      cytoskeleton, we discuss evidence for the role of the cytoskeleton in determining
      myogenic responsiveness. Finally, we analyze evidence that integrin-linked
      signaling pathways, such as those involving protein tyrosine phosphorylation
      cascades and mitogen-activated protein kinases, are required for myogenic tone.

PMID- 11247751
TI  - Use of functional proteomics to investigate PKC epsilon-mediated
      cardioprotection: the signaling module hypothesis.
AB  - The characterization of biological processes on the basis of alterations in the
      cellular proteins, or "proteomic" analysis, is a powerful approach that may be
      adopted to decipher the signaling mechanisms that underlie various
      pathophysiological conditions, such as ischemic heart disease. This review
      represents a prospectus for the implementation of proteomic analyses to delineate
      the myocardial intracellular signaling events that evoke cardioprotection against
      ischemic injury. In concert with this, the manifestation of a protective
      phenotype has recently been shown to involve dynamic modulation of protein kinase
      C-epsilon (PKC epsilon) signaling complexes (Ping P, Zhang J, Pierce WM Jr, and
      Bolli R. Circ Res 88: 59--62, 2001). Accordingly, "the signaling module
      hypothesis" is formulated as a plausible mechanism by which multipurpose stress
      activated proteins and signaling kinases may function collectively to facilitate
      the genesis of cardioprotection.

PMID- 11247752
TI  - RI in central retinal artery as assessed by CDI does not correspond to retinal
      vascular resistance.
AB  - The aim of the present study was to investigate the association between
      ultrasound Doppler measurements of resistive index (RI) in the central retinal
      artery and retinal vascular resistance (R) assessed with laser Doppler
      velocimetry, vessel size measurement, and calculation of ocular perfusion
      pressure (PP) in healthy subjects. An increase in vascular resistance was induced
      by inhalation of 100% O(2). During hyperoxia no significant changes in PP were
      observed. Mean flow velocity in main retinal veins was reduced by -27.5 +/- 2.0%.
      The average decrease in diameter was -11.5 +/- 1.0%. R, which was calculated as
      the ratio of PP to flow rate, increased by 97.6 +/- 7.7%. RI increased as well,
      but the effect was much smaller (6.6 +/- 2.2%). In addition, a negative
      correlation was found between baseline values of R and RI (r = -0.83). During
      hyperoxia R and RI were not associated. In conclusion, our data indicate that RI
      as assessed with color Doppler imaging in the central retinal artery is not an
      adequate measure of R.

PMID- 11247753
TI  - Role of nitric oxide in the cerebrovascular and thermoregulatory response to
      interleukin-1 beta.
AB  - Central administration of interleukin-1 beta (IL-1 beta) increases cerebral blood
      flow (CBF) and body temperature, in part, through the production of
      prostaglandins. In previous studies, the temporal relationship between these
      effects of IL-1 beta have not been measured. In this study, we hypothesized that
      the increase in CBF occurs before any change in brain or body temperature and
      that the cerebrovascular and thermoregulatory effects of IL-1 beta would be
      attenuated by inhibiting the production of nitric oxide (NO). Adult male rats
      received 100 ng intracerebroventricular (icv) injection of IL-1 beta, and
      cortical CBF (cCBF) was measured by laser-Doppler in the contralateral cerebral
      cortex. A central injection of IL-1 beta caused a rapid increase in cCBF to 133
      +/- 12% of baseline within 15 min and to an average of 137 +/- 12% for the
      remainder of the 3-h experiment. Brain and rectal temperature increased by 0.4 +/
      0.2 and 0.5 +/- 0.2 degrees C, but not until 45 min after IL-1 beta
      administration. Pretreatment with N(omega)-nitro-L-arginine methyl ester (L-NAME;
      5 mg/kg iv) completely prevented the changes in cCBF and brain and rectal
      temperature induced by IL-1 beta. L-Arginine (150 mg/kg iv) partially reversed
      the effects of L-NAME and resulted in increases in both cCBF and temperature.
      These findings suggest that the vasodilatory effects of IL-1 beta in the cerebral
      vasculature are independent of temperature and that NO plays a major role in both
      the cerebrovascular and thermoregulatory effects of centrally administered IL-1
      beta.

PMID- 11247754
TI  - Both central command and exercise pressor reflex reset carotid sinus baroreflex.
AB  - In decerebrate unanesthetized cats, we determined whether either "central
      command," the exercise pressor reflex, or the muscle mechanoreceptor reflex reset
      the carotid baroreflex. Both carotid sinuses were vascularly isolated, and the
      carotid baroreceptors were stimulated with pulsatile pressure. Carotid baroreflex
      function curves were determined for aortic pressure, heart rate, and renal
      vascular conductance. Central command was evoked by electrical stimulation of the
      mesencephalic locomotor region (MLR) in cats that were paralyzed. The exercise
      pressor reflex was evoked by statically contracting the triceps surae muscles in
      cats that were not paralyzed. Likewise, the muscle mechanoreceptor reflex was
      evoked by stretching the calcaneal tendon in cats that were not paralyzed. We
      found that each of the three maneuvers shifted upward the linear relationship
      between carotid sinus pressure and aortic pressure and heart rate. Each of the
      maneuvers, however, had no effect on the slope of these baroreflex function
      curves. Our findings show that central command arising from the MLR as well as
      the exercise pressor reflex are capable of resetting the carotid baroreflex.

PMID- 11247755
TI  - Targeted disruption of ICAM-1, P-selectin genes improves cardiac function and
      survival in TNF-alpha transgenic mice.
AB  - We have developed a transgenic mouse model in which tumor necrosis factor (TNF)
      alpha is overexpressed exclusively in the heart under the regulation of the alpha
      myosin heavy chain promoter. These animals develop chronic heart failure
      associated with severe leukocyte infiltration in both the atria and the
      ventricles. The purpose of this study was to investigate the role of adhesion
      molecules in mediating cardiac dysfunction in the TNF-alpha transgenic model. TNF
      alpha transgenic mice were bred with mice null for intercellular adhesion
      molecule (ICAM)-1 and P-selectin genes to obtain a lineage of ICAM-1 and P
      selectin null mice with selective overexpression of TNF-alpha in the heart. TNF
      alpha transgenic animals showed marked upregulation of ICAM-1 mRNA and protein;
      however, P-selectin mRNA and protein remained undetectable despite chronic TNF
      overexpression. Cardiac function was markedly improved in the ICAM-1(-/-), P
      selectin(-/-), TNF-alpha transgenic group versus the ICAM(+/+), P-selectin(+/+),
      TNF-alpha transgenic group. Kaplan-Meier survival curves showed statistically
      significant prolonged survival in the ICAM-1(-/-), P-selectin(-/-), TNF-alpha
      transgenic animals. These data suggest that ICAM-1 mediates at least in part the
      cardiac dysfunction induced by TNF-alpha expression by cardiac myocytes.

PMID- 11247756
TI  - Infinite number of solutions to the hemodynamic inverse problem.
AB  - Investigators have had much success solving the "hemodynamic forward problem,"
      i.e., predicting pressure and flow at the entrance of an arterial system given
      knowledge of specific arterial properties and arterial system topology. Recently,
      the focus has turned to solving the "hemodynamic inverse problem," i.e.,
      inferring mechanical properties of an arterial system from measured input
      pressure and flow. Conventional methods to solve the inverse problem rely on
      fitting to data simple models with parameters that represent specific mechanical
      properties. Controversies have arisen, because different models ascribe pressure
      and flow to different properties. However, an inherent assumption common to all
      model-based methods is the existence of a unique set of mechanical properties
      that yield a particular pressure and flow. The present work illustrates that
      there are, in fact, an infinite number of solutions to the hemodynamic inverse
      problem. Thus a measured pressure-flow pair can result from an infinite number of
      different arterial systems. Except for a few critical properties, conventional
      approaches to solve the inverse problem for specific arterial properties are
      futile.

PMID- 11247757
TI  - Platelet hyperactivity and abnormal Ca(2+) homeostasis in diabetes mellitus.
AB  - We sought to determine the mechanisms for hyperactivity and abnormal platelet
      Ca(2+) homeostasis in diabetes. The glycosylated Hb (HbA(1c)) level was used as
      an index of glycemic control. Human platelets were loaded with Ca- green-fura
      red, and cytosolic Ca(2+) ([Ca(2+)](i)) and aggregation were simultaneously
      measured. In the first series of experiments, the platelets from diabetic and
      normal subjects were compared for the ability to release Ca(2+) or to promote
      Ca(2+) influx. A potent and relatively specific inhibitor of Na(+)/Ca(2+)
      exchange, 5-(4-chlorobenzyl)-2',4'-dimethylbenzamil (CB-DMB), increased the
      second phase of thrombin-induced Ca(2+) response, suggesting that the
      Na(+)/Ca(2+) exchanger works in the forward mode to mediate Ca(2+) efflux. In
      contrast, in the platelets from diabetics, CB-DMB decreased the Ca(2+) response,
      indicating that the Na(+)/Ca(2+) exchanger works in the reverse mode to mediate
      Ca(2+) influx. In the second series of experiments we evaluated the direct effect
      of hyperglycemia on platelets in vitro. We found that thrombin- and collagen
      induced increases in [Ca(2+)](i) and aggregation were not acutely affected by
      high glucose concentrations of 45 mM. However, when the platelet-rich plasma was
      incubated with a high glucose concentration at 37 degrees C for 24 h, the second
      phase after thrombin activation was inhibited by CB-DMB. In addition, collagen
      stimulated [Ca(2+)](i) response and aggregation were also increased. Thus in
      diabetes the direction and activity of the Na(+)/Ca(2+) exchanger is changed,
      which may be one of the mechanisms for the increased platelet [Ca(2+)](i) and
      hyperactivity. Prolonged hyperglycemia in vitro can induce similar changes,
      suggesting hyperglycemia per se may be the factor responsible for the platelet
      hyperactivity in diabetes.

PMID- 11247758
TI  - Contributions of prostacyclin and nitric oxide to carbon monoxide-induced
      cerebrovascular dilation in piglets.
AB  - Carbon monoxide (CO) is an endogenous dilator in the newborn cerebral
      microcirculation. Other dilators include prostanoids and nitric oxide (NO), and
      interactions among the systems are likely. Experiments on anesthetized piglets
      with cranial windows address the hypothesis that CO-induced dilation of pial
      arterioles involves interaction with the prostanoid and NO systems. Topical
      application of CO or the heme oxygenase substrate heme-L-lysinate (HLL) produced
      dilation. Indomethacin, N(omega)-nitro-L-arginine (L-NNA), and either iberiotoxin
      or tetraethylammonium chloride (TEA) were used to inhibit prostanoids, NO, and
      Ca(2+)-activated K(+) (K(Ca)) channels, respectively. Indomethacin, L-NNA,
      iberiotoxin, or TEA blocked cerebral vasodilation to CO and HLL. Vasodilations to
      both CO and HLL were returned to indomethacin-treated piglets by topical
      application of iloprost. Vasodilations to both CO and HLL were returned to L-NNA
      treated piglets by sodium nitroprusside but not iloprost. In iberiotoxin- or TEA
      treated piglets, dilations to CO and HLL could not be restored by either iloprost
      or sodium nitroprusside. The dilator actions of CO involve prostacyclin and NO as
      permissive enablers. The permissive actions of prostacyclin and NO may alter the
      K(Ca) channel response to CO because neither iloprost nor sodium nitroprusside
      could restore dilation to CO when these channels were blocked.

PMID- 11247759
TI  - Nonnoradrenergic mechanism of reflex cutaneous vasoconstriction in men.
AB  - We tested for a nonnoradrenergic mechanism of reflex cutaneous vasoconstriction
      with whole body progressive cooling in seven men. Forearm sites (<1 cm(2)) were
      pretreated with: 1) yohimbine (Yoh; 5 mM id) to antagonize alpha-adrenergic
      receptors, 2) Yoh plus propranolol (5 mM Yoh-1 mM PR id) to block alpha- and beta
      adrenergic receptors, 3) iontophoretic application of bretylium tosylate (BT) to
      block all sympathetic vasoconstrictor nerve effects, or 4) intradermal saline.
      Skin blood flow was measured by laser Doppler flowmetry and arterial pressure by
      finger photoplethysmography; cutaneous vascular conductance (CVC) was indexed as
      the ratio of the two. Whole body skin temperature (T(SK)) was controlled at 34
      degrees C (water-perfused suit) for 10 min and then lowered to 31 degrees C over
      15 min. During cooling, vasoconstriction was blocked at BT sites (P > 0.05). CVC
      at saline sites fell significantly beginning at T(SK) of 33.4 +/- 0.01 degrees C
      (P <0.05). CVC at Yoh-PR sites was significantly reduced beginning at TSK of 33.0
      +/- 0.01 degrees C (P < 0.05). After cooling, iontophoretic application of
      norepinephrine (NE) confirmed blockade of adrenergic receptors by Yoh-PR. Because
      the effects of NE were blocked at sites showing significant reflex
      vasoconstriction, a nonnoradrenergic mechanism in human skin is indicated,
      probably via a sympathetic cotransmitter.

PMID- 11247760
TI  - Interstitial exclusion of positively and negatively charged IgG in rat skin and
      muscle.
AB  - Volume exclusion, i.e., the space not available for a specific probe, may be
      dependent on the probe charge. Therefore, interstitial exclusion was measured for
      positively and negatively charged immunoglobulin (IgG) in skin and muscle of rats
      by using a continuous infusion method (30). Steady-state concentration of (125)I
      labeled IgG 1 (pI = 8.7) and (131)I- labeled IgG 4 (pI = 6.6) was maintained by
      infusion of tracer for 120-168 h with an implanted osmotic pump. At the end of
      the infusion period and before tissue sampling, the rat was anesthetized and
      nephrectomized, and (51)Cr-labeled EDTA was injected and allowed 4 h for
      equilibration to measure interstitial fluid volume (V(i)). Interstitial fluid was
      isolated from skin and muscle by using nylon wicks implanted post mortem. The
      relative IgG available space was measured as the ratio between labeled IgG and
      (51)Cr-labeled EDTA wick fluid equivalent spaces, and relative excluded volume
      fraction (V(e)/V(i)) was calculated as 1--V(a)/V(i). V(e)/V(i) in hindlimb skin
      averaged 0.37 +/- 0.05 (SE) and 0.65 +/- 0.06 (P < 0.01) for IgG 1 and 4,
      respectively, with corresponding figures of 0.24 +/- 0.05 and 0.51 +/- 0.04 (P <
      0.01) in hindlimb muscle (n = 9 for both tissues). These experiments suggest that
      fixed negative charges, most likely glycosaminoglycans, influence distribution of
      macromolecules in the interstitium and therefore affect interstitial fluid
      balance.

PMID- 11247762
TI  - Constructive and destructive addition of forward and reflected arterial pulse
      waves.
AB  - Although the physics of arterial pulse wave propagation and reflection is well
      understood, there is considerable debate as to the effect of reflection on
      vascular input impedance (Z(in)), pulsatile pressure, and stroke work (SW). This
      may be related to how reflection is studied. Conventionally, reflection is
      experimentally abolished (thus radically changing unrelated parameters), or a
      specific model is assumed from which reflection can be removed (yielding model
      dependent results). The present work proposes a simple, model-independent method
      to evaluate the effect of reflection directly from measured pulsatile pressure
      (P) and flow (Q). Because characteristic impedance (Z(0)) is Z(in) in the absence
      of reflection, the P with reflection theoretically removed can be calculated from
      Q x Z(0). Applying this insight to an illustrative case indicates that reflection
      has the least effect on P and SW at normal pressure but a greater effect with
      vasodilation and vasoconstriction. Z(in), P, and SW are increased or decreased
      depending on the relative amount of constructive and destructive addition of
      forward and reflected arterial pulse waves.

PMID- 11247761
TI  - A common mechanism for concurrent changes of diastolic muscle length and systolic
      function in intact hearts.
AB  - Mechanical properties of the myocardium at end diastole have been thought to be
      dominated by passive material properties rather than by active sarcomere cross
      bridge interactions. This study tested the hypothesis that residual cross-bridges
      significantly contribute to end-diastolic mechanics in vivo and that changes in
      end-diastolic cross-bridge interaction parallel concurrent changes in systolic
      cross-bridge interaction. Open-chest anesthetized pigs were treated with
      intracoronary verapamil (n = 7) or 2,3-butanedione monoxime (BDM; n = 8).
      Regional left ventricular external work and end-diastolic pressure (EDP) versus
      end-diastolic segment length (EDL) relations were determined in the treated and
      untreated regions of each heart. Both agents reduced external work of treated
      regions to 31-38% of baseline and concurrently shifted EDP versus EDL relations
      to the right (i.e., greater EDL at a given EDP) by an average of 5% (P < 0.05).
      During washout of the drugs, EDP versus EDL returned to baseline in parallel with
      recovery of external work. Sarcomere length, measured by transmission electron
      microscopy in BDM-treated and untreated regions of the same hearts after
      diastolic arrest and perfusion fixation, was 8% greater in BDM-treated regions (P
      < 0.01). We concluded that residual diastolic cross-bridges significantly and
      reversibly influence end-diastolic mechanics in vivo. Alterations of end
      diastolic and systolic cross-bridge interactions occur in parallel.

PMID- 11247763
TI  - Angiotensin II stimulates cardiac L-type Ca(2+) current by a Ca(2+)- and protein
      kinase C-dependent mechanism.
AB  - Angiotensin II (ANG II) evokes positive inotropic responses in various species.
      However, the effects of this peptide on L-type Ca(2+) currents (I(Ca)) are still
      controversial. We report in this study that the effects of ANG II on I(Ca) differ
      depending on the mode of patch-clamp technique used, standard whole cell (WC) or
      perforated patch (PP). No significant effects of ANG II (0.5 microM) were
      observed when WC in cells dialyzed with high EGTA was used. However, when the
      intracellular milieu was preserved using PP, ANG II induced a significant 77 +/-
      6% increase in I(Ca) (-2.2 +/- 0.3 in control and -3.9 +/- 0.6 pA/pF in ANG II, n
      = 8, P < 0.05). When WC was used in cells dialyzed with low Ca(2+) buffer
      capacity (EGTA 0.1 mM), ANG II was able to induce an increase in I(Ca) (-3.5 +/-
      0.3 in control vs. -4.8 +/- 0.4 pA/pF in ANG II, n = 13, P < 0.05). This increase
      was prevented when the cells were also dialyzed with the protein kinase C (PKC)
      inhibitor chelerythrine (50 microM) or calphostin C (1 microM). The above results
      allow us to conclude that strong intracellular Ca(2+) buffering prevents the
      physiological actions of ANG II on cardiac I(Ca), which are also dependent on
      activation of PKC.

PMID- 11247764
TI  - Regulation of B(2)-kinin receptors by glucose in vascular smooth muscle cells.
AB  - The development of vascular disease is accelerated in hyperglycemic states.
      Vascular injury plays a pivotal role in the progression of atherosclerotic
      vascular disease in diabetes, which is characterized by increased vascular smooth
      muscle cell (VSMC) proliferation and extracellular matrix accumulation. We
      previously reported that diabetes alters the activity of the kallikrein-kinin
      system and results in the upregulation of kinin receptors in the vessel wall. To
      determine whether glucose can directly influence the regulation of kinin
      receptors, the independent effect of high glucose (25 mM) on B(2)-kinin receptors
      (B2KR) in VSMC was examined. A threefold increase in B2KR protein levels and a
      40% increase in B2KR surface receptors were observed after treatment with high
      glucose after 24 h. The mRNA levels of B2KR were also significantly increased by
      high glucose as early as 4 h later. To elucidate the cellular mechanisms by which
      glucose regulates B2KR, we examined the role of protein kinase C (PKC). High
      glucose increased total PKC activity and resulted in the translocation of
      conventional PKC isoforms (beta(1) and beta(2)), novel (epsilon), and atypical
      (zeta) PKC isoforms into the membrane. Inhibition of PKC activity prevented the
      increase in B2KR levels induced by ambient high glucose. These findings provide
      the first evidence that glucose regulates the expression of B(2) receptors in
      VSMC and provide a rationale to further study the interaction between glucose and
      kinins on the pathogenesis of atherosclerotic vascular disease in diabetes.

PMID- 11247765
TI  - Remodeling of the zero-stress state of femoral arteries in response to flow
      overload.
AB  - The goal of this study is to quantitatively describe the remodeling of the zero
      stress state of the femoral artery in flow overload. Increased blood flow,
      approximately as a unit step change, was imposed on the femoral artery by making
      an arteriovenous (a-v) fistula with the epigastric vein. The a-v fistula was
      created in the right leg of 36 rats, which were divided equally into six groups
      (2 days and 1, 2, 4, 8, and 12 wk after the fistula). The vessels in the left leg
      were used as controls without operative trauma. The in vivo blood pressure, flow,
      and femoral outer diameter and the in vitro zero-stress state geometry were
      measured. The in vivo shear rate at the endothelial surface increased
      approximately as a step function by approximately 83%, after 2 days, compared
      with the control artery. The arterial luminal and wall area significantly
      increased postsurgically from 0.15 +/- 0.02 and 0.22 +/- 0.02 mm(2) to 0.28 +/-
      0.04 and 0.31 +/- 0.05 mm(2), respectively, after 12 wk. The wall thickness did
      not change significantly over time (P > 0.1). The opening angle decreased to 82
      +/- 4.2 degrees postsurgically when compared with controls (102 +/- 4.4) after 12
      wk and correlated linearly with the thickness-to-radius ratio. Histological
      analysis revealed vascular smooth muscle cell growth. The remodeling data are
      expressed mathematically in terms of indicial functions, i.e., change of a
      particular feature of a blood vessel in response to a unit step change of blood
      flow. The indicial function approach provides a quantitative description of the
      remodeling process in the blood vessel wall.

PMID- 11247766
TI  - Aortic depressor nerve unmyelinated fibers in spontaneously hypertensive rats.
AB  - The objective of the present study was to compare the morphology of the
      unmyelinated fibers in the aortic depressor nerves (ADN) of spontaneously
      hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). In anesthetized rats, the
      ADN was identified by its spontaneous activity synchronous with the arterial
      pulses. Thin sections of the proximal and distal segments of the ADN were
      analyzed by electron microscopy, and a morphometric study of the unmyelinated
      fibers and Schwann cells was performed. The proximal segments of WKY and SHR ADN
      contain an average of 335 +/- 68 and 130 +/- 14 unmyelinated fibers, respectively
      (P < 0.05), and the distal segments contain an average of 337 +/- 46 and 242 +/-
      77 unmyelinated fibers, respectively (P < 0.05). The distribution of the
      diameters of unmyelinated fibers was unimodal for both strains, with the
      histogram from the SHR significantly shifted to the left. Because the
      unmyelinated fibers play a role in the tonic inhibition of the medullary
      vasomotor centers, especially in the presence of hypertension, the morphological
      differences observed in the ADN from SHR may account, at least in part, for the
      blunted baroreflex of SHR.

PMID- 11247767
TI  - Effect of NO donors on protein phosphorylation in intact vascular and nonvascular
      smooth muscles.
AB  - It is generally well accepted that nitrovasodilator-induced relaxation of
      vascular smooth muscle involves elevation of cGMP and activation of a specific
      cGMP-dependent protein kinase [protein kinase G (PKG)]. However, the protein
      targets of PKG and the underlying mechanisms by which this kinase leads to a
      relaxant response have not been elucidated. Several types of smooth muscle,
      including rat myometrium and vas deferens, are not relaxed by sodium
      nitroprusside, even at concentrations that produce marked elevation of cGMP and
      activation of PKG. The main objective of our studies was to compare PKG-mediated
      protein phosphorylation in intact rat aorta, rat myometrium, and rat vas deferens
      using two-dimensional gel electrophoresis. In intact rat aorta, seven PKG
      substrates were detected during relaxation of the tissue. None of the PKG
      substrates identified in the rat aorta appeared to be phosphorylated in the
      myometrium or vas deferens after administration of various cGMP-elevating agents.
      Thus the failure of the rat myometrium and rat vas deferens to relax in the face
      of cGMP elevation and PKG activation may be due to a lack of PKG substrate
      phosphorylation.

PMID- 11247768
TI  - Differential dynamic baroreflex regulation of cardiac and renal sympathetic nerve
      activities.
AB  - Although regional difference in sympathetic efferent nerve activity has been well
      investigated, whether this regional difference exists in the dynamic baroreflex
      regulation of sympathetic nerve activity remains uncertain. In anesthetized,
      vagotomized, and aortic-denervated rabbits, we isolated carotid sinuses and
      randomly perturbed intracarotid sinus pressure (CSP) while simultaneously
      recording cardiac (CSNA) and renal sympathetic nerve activities (RSNA). The
      neural arc transfer function from CSP to CSNA and that from CSP to RSNA revealed
      high-pass characteristics. The increasing slope of the transfer gain in the
      frequencies between 0.03 and 0.3 Hz was significantly greater for CSNA than for
      RSNA (2.96 +/- 0.72 vs. 1.64 +/- 0.73 dB/octave, P < 0.01, n = 9). The difference
      was hardly explained by the difference in static nonlinear characteristics of CSP
      CSNA and CSP-RSNA relationships or by the difference in conduction velocities in
      the multifiber recording. These results indicate that the central processing in
      the brain stem differs between CSNA and RSNA. The neural arc of the baroreflex
      may exert differential effects on the heart and kidney in response to dynamic
      baroreflex activation.

PMID- 11247769
TI  - Hypertonic saline-dextran suppresses burn-related cytokine secretion by
      cardiomyocytes.
AB  - Whereas hypertonic saline-dextran (HSD, 7.5% NaCl in 6% D70) improves cardiac
      contractile function after burn trauma, the mechanisms of HSD-related
      cardioprotection remain unclear. We recently showed that cardiomyocytes secrete
      tumor necrosis factor-alpha (TNF-alpha), a response that was enhanced by burn
      trauma. This study addressed the question: does HSD modulate cardiac
      contraction/relaxation by altering cardiomyocyte TNF-alpha secretion? Wistar
      Furth rats (325 g) were given a burn injury over 40% of the total body surface
      area and were then randomized to receive a bolus of either isotonic saline or HSD
      (4 ml/kg, n = 14 rats/group). Sham burn rats were given either isotonic saline or
      HSD (n = 14 rats/group) to provide appropriate controls for the two burn groups.
      Hearts were isolated 24 h postburn for either Langendorff perfusion (n = 8
      hearts/group) or to prepare cardiomyocytes (n = 6 hearts/group). Myocytes were
      stimulated with lipopolysaccharide (LPS) (0, 10, 25, or 50 microg for 18 h) to
      measure cytokine secretion. Burn trauma increased myocyte TNF-alpha and
      interleukin-1 beta and -6 secretion, exacerbated cytokine response to LPS
      stimulus, and impaired cardiac contraction. HSD treatment of burns decreased
      cardiomyocyte cytokine secretion, decreased responsiveness to LPS challenge with
      regard to cytokine secretion, and improved ventricular function. These data
      suggest that HSD mediates cardioprotection after burn trauma, in part, by
      downregulating cardiomyocyte secretion of inflammatory cytokines.

PMID- 11247770
TI  - Dynamic sympathetic control of atrioventricular conduction time and heart period.
AB  - Although power spectra of R-R and P-R intervals in response to random respiration
      show similar frequency distributions, the way in which dynamic sympathetic
      regulation contributes to such similarity remains unknown. We estimated the
      transfer function from sympathetic stimulation to the atrioventricular interval
      (AV conduction time; T(AV)) with and without constant atrial pacing in seven
      anesthetized cats. The transfer function from sympathetic stimulation to T(AV),
      except for absolute gain values, approximated a low-pass filter similar to that
      from sympathetic stimulation to the A-A interval (heart period; T(AA)). The 90%
      rise times did not differ between the T(AA) and T(AV) step responses (32.3 +/-
      1.8 vs. 29.6 +/- 3.2 s). Constant pacing augmented the T(AV) step response (-0.58
      +/- 0.10 vs. -0.86 +/- 0.12 ms/Hz, P < 0.05) without affecting the 90%-rise time.
      These findings suggest that the dynamic characteristics of sympathetic control
      are similar between T(AA) and T(AV) despite the different electrophysiological
      mechanisms determining T(AA) and T(AV). A numerical simulation indicated that if
      the dynamic characteristics of the sympathetic control do not match between T(AA)
      and T(AV), a critical condition for initiation of reentrant tachycardia would be
      encountered.

PMID- 11247771
TI  - Differential effects of caspase inhibitors on endotoxin-induced myocardial
      dysfunction and heart apoptosis.
AB  - Endotoxin is one of the major factors causing myocardial depression and death
      during sepsis in humans. Recently, it was reported that endotoxin may induce
      cardiomyocyte apoptosis. Also, multiple caspase activation has been implicated in
      endotoxin-induced apoptosis in several organ systems. In this study, we
      investigated whether endotoxin would increase myocardial caspase activities and
      evaluated the effects of in vivo administration (3 mg/kg) of the broad-spectrum
      caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone(z-VAD.fmk),
      the caspase-3-like inhibitor benzyloxycarbonyl-Asp-Glu-Val-Asp-chloromethylketone
      (z-DEVD.cmk), and the caspase-1-like inhibitor acetyl-Tyr-Val-Ala-Asp
      chloromethylketone (Ac-YVAD. fmk), on endotoxin-induced myocardial dysfunction
      and apoptosis. Endotoxin administration (10 mg/kg iv) induced myocardial
      contractile dysfunction that was associated with caspase activity increases and
      nuclear apoptosis. Broad-spectrum z-VAD.fmk and z-DEVD.cmk improved endotoxin
      induced myocardial dysfunction and reduced caspase activation and nuclear
      apoptosis when given immediately and 2 h after endotoxin. In contrast, no effects
      of Ac-YVAD.fmk were observed on myocardial function and caspase-induced
      apoptosis. Administration of caspase inhibitors 4 h after endotoxin treatment was
      not able to protect the rat heart from myocardial dysfunction and nuclear
      apoptosis. These observations provide evidence that in our model, caspase
      activation plays a role in endotoxin-induced myocardial apoptosis. Caspase
      inhibition strategy may represent a therapeutic approach to endotoxin-induced
      myocardial dysfunction.

PMID- 11247772
TI  - Juxtacrine effects of IL-1 alpha precursor promote iNOS expression in vascular
      smooth muscle cells.
AB  - After injury to the blood vessel wall, vascular smooth muscle cells (SMC)
      synthesize interleukin (IL)-1 and inducible nitric oxide (NO) synthase (iNOS).
      The present study tested whether endogenous production of IL-1 alpha stimulates
      iNOS expression in vascular SMC, and assessed whether IL-1 alpha exerts autocrine
      effects on the cells producing IL-1 alpha or juxtacrine effects on cells that
      contact the IL-1 alpha producing cells. Rat aortic SMC were transiently
      transfected with expression plasmids encoding either IL-1 alpha precursor, which
      localizes to the plasma membrane, or mature IL-1 alpha, which remains cytosolic.
      iNOS mRNA levels, determined by RT-PCR, and production of nitrite, a stable
      oxidation product of NO, were markedly elevated in SMC overexpressing IL-1 alpha
      precursor, and modestly elevated in SMC overexpressing mature IL-1 alpha,
      relative to SMC transfected with vector alone. Exposure to exogenous IL-1 beta or
      TNF-alpha further stimulated iNOS gene expression in SMC producing IL-1 alpha;
      low levels of IL-1 beta (20 pg/ml) were effective in SMC transfected with IL-1
      alpha precursor plasmid, whereas SMC transfected with mature IL-1 alpha plasmid
      or vector alone required higher concentrations of IL-1 beta (200 and 2,000 pg/ml,
      respectively). The increases in iNOS mRNA levels and NO production in SMC
      overexpressing IL-1 alpha precursor were prevented by exogenous IL-1 receptor
      antagonist, suggesting that these effects were mediated by the type I IL-1
      receptor. Immunostaining studies indicated that IL-1 alpha precursor stimulates
      iNOS gene expression via cell-cell contact. Expression of iNOS was enhanced in
      cells that were in contact with a cell overexpressing IL-1 alpha precursor
      (identified by coexpression of green fluorescent protein), and in cells that were
      overexpressing IL-1 alpha themselves, but only when the cell contacted another
      cell. Together these results indicate that IL-1 alpha precursor acts by cell-cell
      contact as an autocrine and juxtacrine enhancer of iNOS gene expression, inducing
      moderate iNOS expression on its own, and markedly augmenting the responsiveness
      of rat aortic SMC to exogenous cytokines.

PMID- 11247773
TI  - Iodide and bromide inhibit Ca(2+) uptake by cardiac sarcoplasmic reticulum.
AB  - Recent studies indicate that the Ca(2+) permeability of the sarcoplasmic
      reticulum (SR) can be affected by its anionic environment. Additionally, anions
      could directly modulate the SR Ca(2+) pump or the movement of compensatory charge
      across the SR membrane during Ca(2+) uptake or release. To examine the effect of
      anion substitution on cardiac SR Ca(2+) uptake, fluorometric Ca(2+) measurements
      and spectrophotometric ATPase assays were used. Ca(2+) uptake into SR vesicles
      was inhibited in a concentration-dependent manner when Br(-) or I(-) replaced
      extravesicular Cl(-) (when Br(-) completely replaced Cl(-), uptake velocity was
      approximately 70% of control; when I(-) completely replaced Cl(-), uptake
      velocity was approximately 39% of control). Replacement of Cl(-) with SO(2)(-4)
      had no effect on SR uptake. Although both I(-) and Br(-) inhibited net Ca(2+)
      uptake, neither anion directly inhibited the SR Ca(2+) pump nor did they increase
      the permeability of the SR membrane to Ca(2+). Our results support the hypothesis
      that an anionic current that occurs during SR Ca(2+) uptake is reduced by the
      substitution of Br(-) or I(-) for Cl(-).

PMID- 11247774
TI  - Neural blockade during exercise augments central command's contribution to
      carotid baroreflex resetting.
AB  - This investigation was designed to determine central command's role on carotid
      baroreflex (CBR) resetting during exercise. Nine volunteer subjects performed
      static and rhythmic handgrip exercise at 30 and 40% maximal voluntary contraction
      (MVC), respectively, before and after partial axillary neural blockade. Stimulus
      response curves were developed using the neck pressure-neck suction technique and
      a rapid pulse train protocol (+40 to -80 Torr). Regional anesthesia resulted in a
      significant reduction in MVC. Heart rate (HR) and ratings of perceived exertion
      (RPE) were used as indexes of central command and were elevated during exercise
      at control force intensity after induced muscle weakness. The CBR function curves
      were reset vertically with a minimal lateral shift during control exercise and
      exhibited a further parallel resetting during exercise with neural blockade. The
      operating point was progressively reset to coincide with the centering point of
      the CBR curve. These data suggest that central command was a primary mechanism in
      the resetting of the CBR during exercise. However, it appeared that central
      command modulated the carotid-cardiac reflex proportionately more than the
      carotid-vasomotor reflex.

PMID- 11247775
TI  - Severe exercise alters the strength and mechanisms of the muscle metaboreflex.
AB  - Previous studies have shown that in dogs performing mild to moderate treadmill
      exercise, partial graded reductions in hindlimb blood flow cause active skeletal
      muscle to become ischemic and metabolites to accumulate thus evoking the muscle
      metaboreflex. This leads to a substantial reflex increase in mean arterial
      pressure (MAP) mediated almost solely via a rise in cardiac output (CO). However,
      during severe exercise CO is likely near maximal and thus metaboreflex-mediated
      increases in MAP may be attenuated. We therefore evoked the metaboreflex via
      partial graded reductions in hindlimb blood flow in seven dogs during mild,
      moderate, and severe treadmill exercise. During mild and moderate exercise there
      was a large rise in CO (1.5 +/- 0.2 and 2.2 +/- 0.3 l/min, respectively), whereas
      during severe exercise no significant increase in CO occurred. The rise in CO
      caused a marked pressor response that was significantly attenuated during severe
      exercise (26.3 +/- 7.0, 33.2 +/- 5.6, and 12.2 +/- 4.8 mmHg, respectively). We
      conclude that during severe exercise the metaboreflex pressor response mechanisms
      are altered such that the ability of this reflex to increase CO is abolished, and
      reduced pressor response occurs only via peripheral vasoconstriction. This shift
      in mechanisms likely limits the effectiveness of the metaboreflex to increase
      blood flow to ischemic active skeletal muscle. Furthermore, because the
      metaboreflex is a flow-raising reflex and not a pressure-raising reflex, it may
      be most appropriate to describe the metaboreflex magnitude based on its ability
      to evoke a rise in CO and not a rise in MAP.

PMID- 11247777
TI  - Beneficial effects of adenosine A(2a) agonist CGS-21680 in infarcted and stunned
      porcine myocardium.
AB  - Although there are conflicting results on whether adenosine infusion during
      reperfusion alters infarct size, there are several reports that indicate
      adenosine A(2a) agonists reduce infarct size. There are also reports that the
      A(2a) agonist CGS-21680 increases cAMP and contractility in ventricular myocytes.
      The purpose of this study was to determine whether low-dose intracoronary
      infusions of CGS-21680 during reperfusion exert any beneficial effects in
      irreversibly and reversibly injured myocardium. Open-chest pigs were submitted to
      60 min of coronary artery occlusion and 3 h of reperfusion. Treated pigs were
      administered intracoronary CGS-21680 (0.2 microg x kg(-1) x min(-1)) for the
      first 60 min of reperfusion. Pigs submitted to regional stunning (15 min
      ischemia) were treated with intracoronary CGS-21680 (0.15 microg x kg(-1) x min(
      1)) after 2 h of reperfusion. In the infarct protocol, CGS-21680 reduced infarct
      size from 62 +/- 2% of the region at risk to 36 +/- 2%. In stunned myocardium,
      CGS increased load-independent regional preload recruitable stroke work and area
      by > or =70%, but the same infusion in normal myocardium was associated with no
      inotropic effect. Both beneficial effects were associated with little systemic
      hemodynamic effects. These findings suggest that reperfusion infusions of low
      doses of the A(2a) agonist CGS-21680 exert beneficial effects in reversibly and
      irreversibly injured myocardium.

PMID- 11247778
TI  - Effects of simulated ischemia on spiral wave stability.
AB  - Regional hyperkalemia during acute myocardial ischemia is a major factor
      promoting electrophysiological abnormalities leading to ventricular fibrillation
      (VF). However, steep action potential duration restitution, recently proposed to
      be a major determinant of VF, is typically decreased rather than increased by
      hyperkalemia and acute ischemia. To investigate this apparent contradiction, we
      simulated the effects of regional hyperkalemia and other ischemic components
      (anoxia and acidosis) on the stability of spiral wave reentry in simulated two
      dimensional cardiac tissue by use of the Luo-Rudy ventricular action potential
      model. We found that the hyperkalemic "ischemic" area promotes wavebreak in the
      surrounding normal tissue by accelerating the rate of spiral wave reentry, even
      after the depolarized ischemic area itself has become unexcitable. Furthermore,
      wavebreak and fibrillation can be prevented if the dynamical instability of the
      normal tissue is reduced significantly by targeting electrical restitution
      properties, suggesting a novel therapeutic approach.

PMID- 11247776
TI  - Abnormal contraction caused by expression of G(i)-coupled receptor in transgenic
      model of dilated cardiomyopathy.
AB  - Although increased G(i) signaling has been associated with dilated cardiomyopathy
      in humans, its role is not clear. Our goal was to determine the effects of
      chronically increased G(i) signaling on myocardial function. We studied
      transgenic mice that expressed a G(i)-coupled receptor (Ro1) that was targeted to
      the heart and regulated by a tetracycline-controlled expression system. Ro1
      expression for 8 wk resulted in abnormal contractions of right ventricular muscle
      strips in vitro. Ro1 expression reduced myocardial force by >60% (from 35 +/- 3
      to 13 +/- 2 mN/mm(2), P < 0.001). Nevertheless, sensitivity to extracellular
      Ca(2+) was enhanced. The extracellular [Ca(2+)] resulting in half-maximal force
      was lower with Ro1 expression compared with control (0.41 +/- 0.05 vs. 0.88 +/-
      0.05 mM, P < 0.001). Ro1 expression slowed both contraction and relaxation
      kinetics, increasing the twitch time to peak (143 +/- 6 vs. 100 +/- 4 ms in
      control, P < 0.001) and the time to half relaxation (124 +/- 6 vs. 75 +/- 6 ms in
      control, P < 0.001). Increased pacing frequency increased contractile force
      threefold in control myocardium (P < 0.001) but caused no increase of force in
      Ro1-expressing myocardium. When stimulation was interrupted with rests, postrest
      force increased in control myocardium, but there was postrest decay of force in
      Ro1-expressing myocardium. These results suggest that defects in contractility
      mediated by G(i) signaling may contribute to the development of dilated
      cardiomyopathy.

PMID- 11247779
TI  - Stenosis differentially affects subendocardial and subepicardial arterioles in
      vivo.
AB  - The presence of a coronary stenosis results primarily in subendocardial ischemia.
      Apart from the decrease in coronary perfusion pressure, a stenosis also decreases
      coronary flow pulsations. Applying a coronary perfusion system, we compared the
      autoregulatory response of subendocardial (n = 10) and subepicardial (n = 12)
      arterioles (<120 microm) after stepwise decreases in coronary arterial pressure
      from 100 to 70, 50, and 30 mmHg in vivo in dogs (n = 9). Pressure steps were
      performed with and without stenosis on the perfusion line. Maximal arteriolar
      diameter during the cardiac cycle was determined and normalized to its value at
      100 mmHg. The initial decrease in diameter during reductions in pressure was
      significantly larger at the subendocardium. Diameters of subendocardial and
      subepicardial arterioles were similar 10--15 s after the decrease in pressure
      without stenosis. However, stenosis decreased the dilatory response of the
      subendocardial arterioles significantly. This decreased dilatory response was
      also evidenced by a lower coronary inflow at similar average pressure in the
      presence of a stenosis. Inhibition of nitric oxide production with N(G)
      monomethyl-L-arginine abrogated the effect of the stenosis on flow. We conclude
      that the decrease in pressure caused by a stenosis in vivo results in a larger
      decrease in diameter of the subendocardial arterioles than in the subepicardial
      arterioles, and furthermore stenosis selectively decreases the dilatory response
      of subendocardial arterioles. These two findings expand our understanding of
      subendocardial vulnerability to ischemia.

PMID- 11247780
TI  - Conduction left-to-right and right-to-left across the crista terminalis.
AB  - A line of block between the vena cava and the crista terminalis (CT) region is
      important for atrial flutter (AFL), but whether it is fixed or functional is
      controversial. To test the hypothesis that conduction across the CT normally
      occurs, but when block occurs in this region it is functional, we analyzed atrial
      activation during right and left atrial pacing (cycle lengths of 500--130 ms),
      AFL, and atrial fibrillation in 15 dogs with sterile pericarditis and 7 normal
      dogs. Electrograms from 396 right, left, and septal atrial sites were
      simultaneously recorded. Activation across the CT occurred during atrial pacing,
      AFL, and atrial fibrillation. Activation wave fronts from the right to the left
      atrium and vice versa traveled over several routes, including Bachmann's bundle
      and inferior to the inferior vena cava, as well as across the CT. In these
      models, there is no fixed conduction block across the CT, and when block in the
      CT region occurs, as during AFL, it is functional.

PMID- 11247781
TI  - Endothelial vasodilator production by uterine and systemic arteries. VI. Ovarian
      and pregnancy effects on eNOS and NO(x).
AB  - Normal pregnancy and the follicular phase of the ovarian cycle are both estrogen
      dominated physiological states that are characterized by elevations in uterine
      blood flow and endothelial nitric oxide synthase (eNOS) protein expression in the
      uterine artery (UA) endothelium. It is unknown if elevations in mRNA level
      account for the changes in protein or eNOS activity. We tested the hypothesis
      that pregnancy and the follicular phase are associated with increases in eNOS
      mRNA and the consequent elevated expression of eNOS protein results in increased
      circulating nitric oxide (NO) levels. UA were obtained from pregnant (PREG; n =
      8; 110-130 days gestation; term = 145 +/- 3 days), nonpregnant luteal (LUT; n =
      6), nonpregnant follicular (FOL; n = 6), and nonpregnant ovariectomized (OVEX; n
      = 6) sheep. Circulating NO levels were analyzed as total NO(2)-NO(3) (NO(x)).
      Western analysis performed on UA endothelial-isolated proteins demonstrated that
      eNOS protein levels were OVEX = LUT < or = FOL < PREG (P < 0.05), whereas eNOS
      mRNA expression (RT-PCR) in UA endothelial cells obtained by limited collagenase
      digestion was OVEX < LUT < FOL < PREG (P < 0.05). Pregnancy dramatically elevated
      eNOS protein (4.1- to 6.9-fold) and mRNA (2.4- to 6.9-fold) over LUT controls (P
      < 0.01). Circulating NO(x) levels were not altered by ovariectomy or the ovarian
      cycle but were elevated from 4.4 +/- 1.1 microM in LUT to 12 +/- 4, 22 +/- 3, and
      41 +/- 3 microM at 110, 120, and 130 days gestation (P < 0.01). Systemic NO(x)
      levels in singleton (12.5 +/- 1.6 microM) were less (P < 0.01) than in multiple
      (twin 27.6 +/- 6.5 microM; triplet = 46 +/- 10 microM) pregnancies. Therefore,
      the follicular phase and, to a much greater extent, pregnancy are associated with
      elevations in UA endothelium-derived eNOS expression, although significant
      increases in systemic NO(x) levels were only observed in the PREG group (multiple
      > singleton). Thus, although UA endothelial increases in eNOS protein and mRNA
      levels are associated with high estrogen states, increases in local UA NO
      production may require additional eNOS protein activation to play its important
      role in the maintenance of uterine blood flow in pregnancy.

PMID- 11247782
TI  - Endothelial vasodilator production by uterine and systemic arteries. VII.
      Estrogen and progesterone effects on eNOS.
AB  - Uterine blood flow (UBF) and uterine artery endothelial nitric oxide synthase
      (eNOS) expression are greatest during the follicular vs. luteal phase. 17 beta
      Estradiol (E(2)beta) increases UBF and elevates eNOS in ovine uterine but not
      systemic arteries; progesterone (P(4)) effects on E(2)beta changes of eNOS remain
      unclear. Nonpregnant ovariectomized sheep received either vehicle (n = 10), P(4)
      (0.9 g Controlled Internal Drug Release vaginal implants; n = 13), E(2)beta (5
      microg/kg bolus + 6 microg x kg(-1) x day(-1); n = 10), or P(4) + E(2)beta (n =
      12). Reproductive (uterine/mammary) and nonreproductive (omental/renal) artery
      endothelial proteins were procured on day 10, and eNOS was measured by Western
      analysis. P(4) and E(2)beta alone and in combination increased (P < 0.05) eNOS
      expression in uterine artery endothelium (vehicle = 100 +/- 16%, P(4) = 251 +/-
      59%, E(2)beta = 566 +/- 147%, P(4) + E(2)beta = 772 +/- 211% of vehicle). Neither
      omental, renal, nor mammary artery eNOS was altered, demonstrating the local
      nature of steroid-induced maintenance of uterine arterial eNOS. In the myometrial
      microvasculature, eNOS was increased slightly (P = 0.06) with E(2)beta and
      significantly with P(4) + E(2)beta. Systemic NO(x) was increased with P(4) and
      P(4) + E(2)beta, but not E(2)beta, suggesting differential regulation of eNOS
      expression and activity, since P(4) increased eNOS in uterine artery endothelium
      while E(2)beta and the combination further increased eNOS protein.

PMID- 11247784
TI  - Role of leukocyte accumulation and oxygen radicals in ischemia-reperfusion
      induced injury in skeletal muscle.
AB  - The role of leukocytes and nonleukocyte-derived reactive oxygen metabolites
      (ROMs) in reperfusion-induced skeletal muscle injury was determined. Male rats
      received 2 h no-flow hindlimb ischemia-reperfusion (I/R, n = 6) or were rendered
      neutropenic via antineutrophil serum (ANS) before I/R (I/R + ANS, n = 5). Oxygen
      radicals in the absence of neutrophils were tested by administration of
      dimethylthiourea (DMTU) (I/R + ANS + DMTU, n = 5). Perfused capillaries (CD(per))
      and rolling (L(r)), adherent (L(a)), and extravasated leukocytes (L(e)) in the
      extensor digitorum longus muscle were measured every 15 min during 90 min of
      reperfusion using intravital microscopy. The vital dyes bisbenzimide (BB) and
      ethidium bromide (EB) provided direct measures of tissue injury (EB/BB). CD(per)
      decreased immediately on reperfusion in the I/R and I/R + ANS groups. CD(per) in
      the I/R + ANS + DMTU group remained at baseline throughout reperfusion. L(a)
      increased in the I/R group; however, EB/BB was the same between I/R and I/R + ANS
      groups. Injury in the I/R + ANS + DMTU group did not differ from other groups >
      or =60 min, after which EB/BB became significantly lower. L(e) did not differ
      between groups and was highly correlated to tissue injury. The results suggest
      that L(e) lead to parenchymal injury, and ROMs lead to perfusion deficits during
      the early reperfusion period after ischemia.

PMID- 11247783
TI  - High-affinity prorenin binding to cardiac man-6-P/IGF-II receptors precedes
      proteolytic activation to renin.
AB  - Mannose-6-phosphate (man-6-P)/insulin-like growth factor-II (man-6-P/IgF-II)
      receptors are involved in the activation of recombinant human prorenin by
      cardiomyocytes. To investigate the kinetics of this process, the nature of
      activation, the existence of other prorenin receptors, and binding of native
      prorenin, neonatal rat cardiomyocytes were incubated with recombinant, renal, or
      amniotic fluid prorenin with or without man-6-P. Intact and activated prorenin
      were measured in cell lysates with prosegment- and renin-specific antibodies,
      respectively. The dissociation constant (K(d)) and maximum number of binding
      sites (B(max)) for prorenin binding to man-6-P/IGF-II receptors were 0.6 +/- 0.1
      nM and 3,840 +/- 510 receptors/myocyte, respectively. The capacity for prorenin
      internalization was greater than 10 times B(max). Levels of internalized intact
      prorenin decreased rapidly (half-life = 5 +/- 3 min) indicating proteolytic
      prosegment removal. Prorenin subdivision into man-6-P-free and man-6-P-containing
      fractions revealed that only the latter was bound. Cells also bound and activated
      renal but not amniotic fluid prorenin. We concluded that cardiomyocytes display
      high-affinity binding of renal but not extrarenal prorenin exclusively via man-6
      P/IGF-II receptors. Binding precedes internalization and proteolytic activation
      to renin thereby supporting the concept of cardiac angiotensin formation by renal
      prorenin.

PMID- 11247785
TI  - NGF-independent survival of postganglionic sympathetic neurons in neuronal
      vascular smooth muscle cocultures.
AB  - The present study tests the hypothesis that vascular cells promote the survival
      of postganglionic sympathetic neurons in the absence of nerve growth factor
      (NGF). To test this hypothesis, neurons isolated from superior cervical ganglia
      of 2- to 4-day-old rat pups were grown in the absence of NGF and in the absence
      and presence of vascular smooth muscle cells (VSM). Neuronal survival was
      assessed as a function of time in culture. At all time points studied, VSM
      promoted the survival of the neurons. After 5 days in the absence of NGF, 7 +/-
      2% of neurons survived in the absence and 28 +/- 7% survived in the presence of
      VSM. An endothelin receptor antagonist reduced neuronal survival in cocultures
      grown in the absence of NGF. These data indicate that VSM produce factors other
      than NGF that promote the survival of cultured postganglionic sympathetic
      neurons. The data also indicate that endothelin contributes to this effect and
      suggest that endothelin as well as other VSM-derived factors may play a role in
      the development of sympathetic innervation to the vasculature.

PMID- 11247786
TI  - Assessment of segmental wall motion abnormalities using contrast two-dimensional
      echocardiography in awake mice.
AB  - Murine models of cardiac disease are becoming an important tool for studying
      pathophysiological processes. Development of methods to accurately assess
      ventricular function are therefore important. The purpose of this study was to
      evaluate the feasibility of echocardiographic assessment of segmental wall motion
      abnormalities in a murine model of myocardial infarction. Two-dimensional
      contrast (C+) and noncontrast (C-) echocardiography were performed in 76 awake
      mice 2 days before and 2 days after left coronary ligation. The short-axis images
      obtained with two-dimensional echocardiography and corresponding postmortem cross
      sectional histological samples stained with Evans blue dye were each divided into
      16 segments, and all matched segments were examined for correlation between wall
      motion abnormalities and myocardial hypoperfusion. With the use of contrast
      enhancement, the number of visualized segments was significantly increased (base:
      C- 86%, C+ 98%; midpapillary: C- 57%, C+ 89%; apex: C- 30%, C+ 74%). Agreement
      between echocardiographically assessed regional wall motion abnormalities and
      pathologically determined hypoperfusion in basal, midpapillary, and apical levels
      were 90%, 93%, and 93%, respectively. Agreement between echocardiographically
      normal wall motion and pathologically normal findings in basal, midpapillary, and
      apical levels were 99%, 88%, and 71%, respectively. Thus echocardiographic
      assessment of segmental wall motion in awake mice was feasible and the accuracy
      was improved with the use of a contrast agent.

PMID- 11247787
TI  - Heat pretreatment differentially affects cardiac fatty acid accumulation during
      ischemia and postischemic reperfusion.
AB  - We investigated whether the cardioprotection induced by heat stress (HS)
      pretreatment is associated with mitigation of phospholipid degradation during the
      ischemic and/or postischemic period. The hearts, isolated from control rats and
      from heat-pretreated rats (42 degrees C for 15 min) either 30 min (HS0.5-h) or 24
      h (HS24-h) earlier, were subjected to 45 min of no-flow ischemia, followed by 45
      min of reperfusion. Unesterified arachidonic acid (AA) accumulation was taken as
      a measure for phospholipid degradation. Significantly improved postischemic
      ventricular functional recovery was only found in the HS24-h group. During
      ischemia, AA accumulated comparably in control and both HS groups. During
      reperfusion in control and HS0.5-h hearts, AA further accumulated (control hearts
      from 82 +/- 33 to 109 +/- 51 nmol/g dry wt, not significant; HS-0.5h hearts from
      52 +/- 22 to 120 +/- 53 nmol/g dry wt; P < 0.05). In contrast, AA was lower at
      the end of the reperfusion phase in HS24-h hearts than at the end of the
      preceding ischemic period (74 +/- 18 vs. 46 +/- 23 nmol/g dry wt; P < 0.05). Thus
      accelerated reperfusion-induced degradation of phospholipids in control hearts is
      completely absent in HS24-h hearts. Furthermore, the lack of functional
      improvement in HS0.5-h hearts is also associated with a lack of beneficial effect
      on lipid homeostasis. Therefore, it is proposed that enhanced membrane stability
      during reperfusion is a key mediator in the heat-induced cardioprotection.

PMID- 11247789
TI  - Characterization of stretch-activated cation current in coronary smooth muscle
      cells.
AB  - Stretch-activated ion currents were recorded from vascular smooth muscle (VSM)
      after enzymatic isolation of single cells from porcine coronary arterioles. Patch
      pipettes were used to record whole cell current and control cell length. Under
      voltage clamp in physiological saline solution, an inward cation current (I(CAT))
      was activated by 105--135% longitudinal stretch. I(CAT) coincided with an
      increase in intracellular Ca(2+) concentration. Under current clamp, membrane
      depolarization was induced by stretch. The magnitude of I(CAT) varied from -0.8
      to -6.9 pA/pF at a holding potential of -60 mV. I(CAT) was graded with stretch,
      inactivated on release, and could be repeatedly induced. A potassium current
      (I(K)) activated in unstretched cells by depolarization was also enhanced by
      stretch. In Ca(2+)-free bath solution, stretch-induced enhancement of I(K) was
      blocked, but I(CAT) was still present. Hexamethyleneamiloride (50 microM), a
      reputed inhibitor of mechanosensitive channels, blocked I(CAT) and the stretch
      induced increase in I(K) but not basal I(K). Grammostolla spatulata venom
      (1:100,000) blocked basal I(K), blocked stretch-induced increases in I(K), and
      blocked I(CAT). Iberiotoxin, a specific Ca(2+)-activated K(+) channel blocker,
      did not alter I(CAT) but blocked the stretch-induced increase in I(K) and
      increased the magnitude of stretch-induced depolarization. We concluded that
      longitudinal stretch directly activates a cation current and secondarily
      activates a Ca(2+)-activated K(+) current in isolated coronary myocytes. Although
      these two currents would partially counteract each other, the predominance of
      I(CAT) at physiological potentials is likely to explain the depolarization and
      contraction observed in intact coronary VSM during pressure elevation.

PMID- 11247790
TI  - Dichloroacetate improves cardiac efficiency after ischemia independent of changes
      in mitochondrial proton leak.
AB  - Dichloroacetate (DCA) is a pyruvate dehydrogenase activator that increases
      cardiac efficiency during reperfusion of ischemic hearts. We determined whether
      DCA increases efficiency of mitochondrial ATP production by measuring proton leak
      in mitochondria from isolated working rat hearts subjected to 30 min of ischemia
      and 60 min of reperfusion. In untreated hearts, cardiac work and efficiency
      decreased during reperfusion to 26% and 40% of preischemic values, respectively.
      Membrane potential was significantly lower in mitochondria from reperfused (175.6
      +/- 2.2 mV) versus aerobic (185.8 +/- 3.1 mV) hearts. DCA (1 mM added at
      reperfusion) improved recovery of cardiac work (1.9-fold) and efficiency (1.5
      fold) but had no effect on mitochondrial membrane potential (170.6 +/- 2.9 mV).
      At the maximal attainable membrane potential, O(2) consumption (nmol O(2) x mg(
      1) x min(-1)) did not differ between untreated or DCA-treated hearts (128.3 +/-
      7.5 and 120.6 +/- 7.6, respectively) but was significantly greater than aerobic
      hearts (76.6 +/- 7.6). During reperfusion, DCA increased glucose oxidation 2.5
      fold and decreased H(+) production from glucose metabolism to 53% of untreated
      hearts. Because H(+) production decreases cardiac efficiency, we suggest that DCA
      increases cardiac efficiency during reperfusion of ischemic hearts by increasing
      the efficiency of ATP use and not by increasing the efficiency of ATP production.

PMID- 11247788
TI  - Diabetes and hyperglycemia impair activation of mitochondrial K(ATP) channels.
AB  - Hyperglycemia is an important predictor of cardiovascular mortality in patients
      with diabetes. We investigated the hypothesis that diabetes or acute
      hyperglycemia attenuates the reduction of myocardial infarct size produced by
      activation of mitochondrial ATP-regulated potassium (K(ATP)) channels. Acutely
      instrumented barbiturate-anesthetized dogs were subjected to a 60-min period of
      coronary artery occlusion and 3 h of reperfusion. Myocardial infarct size
      (triphenyltetrazolium chloride staining) was 25 +/- 1, 28 +/- 3, and 25 +/- 1% of
      the area at risk (AAR) for infarction in control, diabetic (3 wk after
      streptozotocin-alloxan), and hyperglycemic (15% intravenous dextrose) dogs,
      respectively. Diazoxide (2.5 mg/kg iv) significantly decreased infarct size (10
      +/- 1% of AAR, P < 0.05) but did not produce protection in the presence of
      diabetes (28 +/- 5%) or moderate hyperglycemia (blood glucose 310 +/- 10 mg/dl;
      23 +/- 2%). The dose of diazoxide and the degree of hyperglycemia were
      interactive. Profound (blood glucose 574 +/- 23 mg/dl) but not moderate
      hyperglycemia blocked the effects of high-dose (5.0 mg/kg) diazoxide [26 +/- 3,
      15 +/- 3 (P < 0.05), and 11 +/- 2% (P < 0.05), respectively]. There were no
      differences in systemic hemodynamics, AAR, or coronary collateral blood flow (by
      radioactive microspheres) between groups. The results indicate that diabetes or
      hyperglycemia impairs activation of mitochondrial K(ATP) channels.

PMID- 11247791
TI  - Detection of regional temporal abnormalities in left ventricular function during
      acute myocardial ischemia.
AB  - Echocardiographic diagnosis of myocardial ischemia is based on visualizing
      hypokinesis, which occurs late in the ischemic cascade. We hypothesized that
      temporal changes in endocardial motion may constitute sensitive early markers of
      ischemia. Two protocols were performed in 19 anesthetized pigs. Protocol 1
      included 54 intracoronary balloon occlusions. Transthoracic images were acquired
      at baseline and every 15 s during 5 min of occlusion and reperfusion. In protocol
      2, ischemia was induced in 12 animals by use of graded dobutamine infusion, after
      creating significant partial occlusions without a resting wall motion
      abnormality. Systolic and diastolic endocardial motion was color encoded using
      color kinesis and analyzed using custom software. All ischemic episodes caused
      detectable and reversible changes. The earliest sign of ischemia was tardokinesis
      in 31/54 occlusions, whereas hypokinesis appeared first in 23/54 cases.
      Dobutamine-induced ischemia caused tardokinesis first in 9/12 and hypokinesis in
      3/12 animals. Reversible ischemic changes in regional left ventricular
      performance can be objectively detected using analysis of echocardiographic
      images and will likely improve the early noninvasive diagnosis of acute ischemia.

PMID- 11247792
TI  - Cardiomyopathy in transgenic mice with cardiac-specific overexpression of serum
      response factor.
AB  - Serum response factor (SRF), a member of the MCM1, agamous, deficiens, SRF (MADS)
      family of transcriptional activators, has been implicated in the transcriptional
      control of a number of cardiac muscle genes, including cardiac alpha-actin,
      skeletal alpha-actin, alpha-myosin heavy chain (alpha-MHC), and beta-MHC. To
      better understand the in vivo role of SRF in regulating genes responsible for
      maintenance of cardiac function, we sought to test the hypothesis that increased
      cardiac-specific SRF expression might be associated with altered cardiac
      morphology and function. We generated transgenic mice with cardiac-specific
      overexpression of the human SRF gene. The transgenic mice developed
      cardiomyopathy and exhibited increased heart weight-to-body weight ratio,
      increased heart weight, and four-chamber dilation. Histological examination
      revealed cardiomyocyte hypertrophy, collagen deposition, and interstitial
      fibrosis. SRF overexpression altered the expression of SRF-regulated genes and
      resulted in cardiac muscle dysfunction. Our results demonstrate that sustained
      overexpression of SRF, in the absence of other stimuli, is sufficient to induce
      cardiac change and suggest that SRF is likely to be one of the downstream
      effectors of the signaling pathways involved in mediating cardiac hypertrophy.

PMID- 11247793
TI  - Sodium-induced rise in blood pressure is suppressed by androgen receptor
      blockade.
AB  - Our objective was to test the hypothesis that 1) a high Na (HNa, 3%) diet would
      increase blood pressure (BP) in male Wistar-Kyoto (WKY) and spontaneously
      hypertensive Y chromosome (SHR/y) rat strains in a territorial colony; 2)
      sympathetic nervous system (SNS) blockade using clonidine would lower BP on a HNa
      diet; and 3) prepubertal androgen receptor blockade with flutamide would lower BP
      on a HNa diet. A 2 x 4 factorial design used rat strains (WKY, SHR/y) and
      treatment [0.3% normal Na (NNa), 3% HNa, HNa/clonidine, and HNa/flutamide]. BP
      increased in both strains on the HNa diet (P < 0.0001). There was no significant
      decrease in BP in either strain with clonidine treatment. Androgen receptor
      blockade with flutamide significantly decreased BP in both strains (P < 0.0001)
      and normalized BP in the SHR/y colony. Neither heart rate nor activity could
      explain these BP differences. In conclusion, a Na sensitivity was observed in
      both strains, which was reduced to normotensive values by androgen blockade but
      not by SNS blockade.

PMID- 11247794
TI  - Carbon monoxide wash-in method to determine gas transfer in vascular beds:
      application to rat hindlimb.
AB  - The vascular barrier to gas transfer is an important physiological parameter;
      however, no readily applicable technique exists to quantitate the process. A
      simple technique to measure the permeability-surface area (PS) product for gas
      transfer in vascular beds is proposed using wash in of carbon monoxide (CO) and
      Crone-Renkin analysis. Wash-in experiments were performed on the perfused
      hindlimbs of male Wistar rats (n = 15) by using CO as a surrogate marker for
      oxygen and technetium-99m-labeled albumin as the vascular marker. The use of CO
      and erythrocyte-free perfusate and the collection of outflow samples into tubes
      preloaded with erythrocytes obviated the need for an anaerobic collection device
      or consideration of Hb binding in the analysis. The PS product for CO was
      determined from the early extraction as 0.013 +/- 0.006 ml. s(-1). g(-1).
      Compartmental analysis revealed that the fractional recovery of CO was 0.45 +/-
      0.14 and the volume of distribution was 2.31 +/- 0.76 ml/g. This technique
      detected a small measurable barrier to the transfer of CO across the hindlimb
      vasculature and is potentially applicable to other vascular beds in health and
      disease.

PMID- 11247795
TI  - Regulation of extracellular volume and interstitial fluid pressure in rat bone
      marrow.
AB  - The volume and fluid pressure characteristics of the intact bone marrow is
      incompletely understood. We used microspheres and lipoproteins for measurements
      of intravascular volume (IVV) and EDTA for interstitial fluid volume (IFV) within
      the rat bone marrow. Interstitial fluid pressure (IFP) was determined with
      micropipettes connected to a servo-controlled counter-pressure system. Both the
      microspheres and the lipoproteins yielded estimates of IVV of approximately 1
      ml/100 g. After a brief reactive hyperemia, IVV increased to 2.5 ml/100 g,
      whereas IFV decreased with approximately 1.5 ml/100 g, so that total
      extracellular volume did not change. Baseline bone marrow IFP was 9.7 mmHg. The
      hyperemia led to a transient twofold increase in IFP, whereas a marked blood loss
      decreased IFP by almost one-half. These novel data suggest that extracellular
      volume and IFP within the bone marrow can be measured with tracer methods and the
      micropuncture technique. The responses of IVV, IFV, and IFP during changes in
      blood flow to the bone marrow suggest a tight regulation and are thus compatible
      with those for a low-compliant tissue.

PMID- 11247796
TI  - Human cardiac myosin heavy chain isoforms in fetal and failing adult atria and
      ventricles.
AB  - The goal of this study was to test the hypothesis that the relative amounts of
      the cardiac myosin heavy chain (MHC) isoforms MHC-alpha and MHC-beta change
      during development and transition to heart failure in the human myocardium. The
      relative amounts of MHC-alpha and MHC-beta in ventricular and atrial samples from
      fetal (gestational days 47--110) and nonfailing and failing adult hearts were
      determined. The majority of the fetal right and left ventricular samples
      contained small relative amounts of MHC-alpha (mean < 5% of total MHC). There was
      a small significant decrease in the level of MHC-alpha in the ventricles between
      7 and 12 wk of gestation. Fetal atria expressed predominantly MHC-alpha (mean >
      95%), with MHC-beta being detected in most samples. The majority of adult
      nonfailing right and left ventricular samples had detectable levels of MHC-alpha
      ranging from 1 to 10%. Failing right and left ventricles expressed a
      significantly lower level of MHC-alpha. MHC-alpha comprised approximately 90% of
      the total MHC in adult nonfailing left atria, whereas the relative amount of MHC
      alpha in the left atria of individuals with dilated or ischemic cardiomyopathy
      was approximately 50%. The differences in MHC isoform composition between fetal
      and nonfailing adult atria and between fetal and nonfailing adult ventricles were
      not statistically significant. We concluded that the MHC isoform compositions of
      fetal human atria are the same as those of nonfailing adult atria and that the
      ventricular MHC isoform composition is different between adult nonfailing and
      failing hearts. Furthermore, the marked alteration in atrial MHC isoform
      composition, associated with cardiomyopathy, does not represent a regression to a
      pattern that is uniquely characteristic of the fetal stage.

PMID- 11247798
TI  - Causal linear parametric model for baroreflex gain assessment in patients with
      recent myocardial infarction.
AB  - Spectral and cross-spectral analysis of R-R interval and systolic arterial
      pressure (SAP) spontaneous fluctuations have been proposed for noninvasive
      evaluation of baroreflex sensitivity (BRS). However, results are not in good
      agreement with clinical measurements. In this study, a bivariate parametric
      autoregressive model with exogenous input (ARXAR model), able to divide the R-R
      variability into SAP-related and -unrelated parts, was used to quantify the gain
      (alpha(ARXAR)) of the baroreflex regulatory mechanism. For performance assessing,
      two traditional noninvasive methods based on frequency domain analysis [spectral,
      baroreflex gain by autogressive model (alpha(AR)); cross-spectral, baroreflex
      gain by bivariate autoregressive model (alpha(2AR))] and one based on the time
      domain [baroreflex gain by sequence analysis (alpha(SEQ))] were considered and
      compared with the baroreflex gain by phenylephrine test (alpha(PHE)). The BRS
      evaluation was performed on 30 patients (61 +/- 10 yr) with recent (10 +/- 3
      days) myocardial infarction. The ARXAR model allowed dividing the R-R variability
      (950 +/- 1,099 ms(2)) into SAP-related (256 +/- 418 ms(2)) and SAP-unrelated (694
      +/- 728 ms(2)) parts. alpha(AR) (12.2 +/- 6.1 ms/mmHg) and alpha(2AR) (8.9 +/-
      5.6 ms/mmHg) as well as alpha(SEQ) (12.6 +/- 7.1 ms/mmHg) overestimated BRS
      assessed by alpha(PHE) (6.4 +/- 4.7 ms/mmHg), whereas the ARXAR index gave a
      comparable value (alpha(ARXAR) = 5.4 +/- 3.3 ms/mmHg). All noninvasive methods
      were significantly correlated to alpha(PHE) (alpha(ARXAR) and alpha(SEQ) were
      more correlated than the other indexes). Thus the baroreflex gain obtained
      describing the causal dependence of R-R interval on SAP showed a good agreement
      with alpha(PHE) and may provide additional information regarding the gain
      estimation in the frequency domain.

PMID- 11247797
TI  - Assembly and activation of HK-PK complex on endothelial cells results in
      bradykinin liberation and NO formation.
AB  - Prekallikrein (PK) activation on human umbilical endothelial cells (HUVEC)
      presumably leads to bradykinin liberation. On HUVEC, PK activation requires the
      presence of cell-bound high-molecular-weight kininogen (HK) and Zn(2+). We
      examined the Zn(2+) requirement for HK binding to and the consequences of PK
      activation on endothelial cells. Optimal HK binding (14 pmol/10(6) HUVEC) is seen
      with no added Zn(2+) in HEPES-Tyrode buffer containing gelatin versus 16--32
      microM added Zn(2+) in the same buffer containing bovine serum albumin. The
      affinity and number of HK binding sites on HUVEC are a dissociation constant of
      9.6 +/- 1.8 nM and a maximal binding of 1.08 +/- 0.26 x 10(7) sites/cell (means
      +/- SD). PK is activated to kallikrein by an antipain-sensitive mechanism in the
      presence of HK and Zn(2+) on HUVEC, human microvascular endothelial cells,
      umbilical artery smooth muscle cells, and bovine pulmonary artery endothelial
      cells. Simultaneous with kallikrein formation, bradykinin (5.0 or 10.3 pmol/10(6)
      HUVEC in the absence or presence of lisinopril, respectively) is liberated from
      cell-bound HK. Liberated bradykinin stimulates the endothelial cell bradykinin B2
      receptor to form nitric oxide. Assembly and activation of PK on endothelial cells
      modulates their physiological activities.

PMID- 11247799
TI  - Cytochrome P-450 omega-hydroxylase: a potential O(2) sensor in rat arterioles and
      skeletal muscle cells.
AB  - The purposes of this study were to 1) further evaluate the possible role that
      vasoconstrictor metabolites of cytochrome P-450 (CYP) omega-hydroxylase plays in
      O(2)-induced constriction of arterioles in the rat skeletal muscle
      microcirculation, 2) determine whether omega-hydroxylases are expressed in rat
      cremaster muscle, and 3) determine whether the enzyme is located in the
      parenchyma or the arterioles. O(2)-induced constriction of third-order arterioles
      in the in situ cremaster muscle of Sprague-Dawley rats was significantly
      inhibited by the CYP inhibitors N-methyl-sulfonyl-12,12-dibromododec-11-enamide
      (DDMS; 50 microM) and 17-octadecynoic acid (ODYA; 10 microM). Immunoblot analysis
      with antibody raised against CYP4A protein indicated the presence of
      immunoreactive proteins in the cremaster muscle and in isolated arterioles and
      muscle fibers from this tissue. However, the molecular mass of the immunoreactive
      proteins was 85 kDa instead of the expected 50--52 kDa for CYP4A omega
      hydroxylase isolated from rat liver or kidney. Treatment of the cremaster muscle
      with deglycosidases shifted the bands to the expected range which indicates that
      these proteins are likely glycosylated in skeletal muscle. Immunohistochemistry
      revealed intense staining of both muscle fibers and microvessels in the cremaster
      muscle. The results of this study indicate that O(2) sensing in the skeletal
      muscle microcirculation may be mediated by CYP4A omega-hydroxylases in both
      arterioles and parenchymal cells.

PMID- 11247800
TI  - Influence of timing and magnitude of arterial wave reflection on left ventricular
      relaxation.
AB  - The influence of timing and magnitude of arterial wave reflection (WR) on
      afterload-dependent relaxation was evaluated in patients with a variety of heart
      diseases (group 1, age < 30 yr; group 2, age > 40 yr) and in dogs. While both
      femoral arteries were compressed (FC), WR returned just after the dicrotic notch
      (early diastole) in group 1 but before the dicrotic notch (late systole) in group
      2. The time constant of the left ventricular pressure decay (tau) was shortened
      during FC in group 1, whereas it was prolonged in group 2. In dogs, a
      constriction of the thoracic aorta induced a late systolic augmentation of WR
      with a prolongation of tau (cf. group 2), whereas constriction of the lower
      abdominal aorta induced an early diastolic augmentation of WR with a shortening
      of tau (cf. group 1). With aortic constriction, coronary flow increased, and
      there was a close correlation between the peak change in backward aortic pressure
      and that in coronary flow regardless of the timing of WR. Thus the time at which
      WR returns during the cardiac cycle may have an important effect on left
      ventricular relaxation and coronary flow.

PMID- 11247801
TI  - The role of ANG II and endothelin-1 in exercise-induced diastolic dysfunction in
      heart failure.
AB  - The diastolic dysfunction present at rest in congestive heart failure (CHF) is
      exacerbated during exercise (Ex). Increases in circulating ANG II and endothelin
      1 (ET-1) during Ex may contribute to this response. We assessed the effect of Ex
      on circulating plasma levels of ANG II and ET-1 and left ventricular (LV)
      dynamics before and after pacing-induced CHF at rest and during Ex in nine
      conscious, instrumented dogs. Before CHF, there were modest increases in
      circulating levels of ANG II (but not ET-1) during Ex. LV diastolic performance
      was enhanced during Ex with decreases in the time constant of LV relaxation
      (tau), LV end-systolic volume (V(ES)), and LV minimum pressure with a downward
      shift of the LV early diastolic portion of the pressure-volume (P-V) loop. This
      produced an increase in peak LV filling rate without an increase in mean left
      atrial (LA) pressure. After CHF, the resting values of ANG II and ET-1 were
      elevated and increased to very high levels during Ex. After CHF, mean LA
      pressure, tau, and LV minimum pressure were elevated at rest and increased
      further during Ex. Treatment with L-754,142, a potent ET-1 antagonist, or
      losartan, an ANG II AT(1)-receptor blocker, decreased these abnormal Ex responses
      in CHF more effectively than an equally vasodilatory dose of sodium
      nitroprusside. Combined treatment with both ANG II- and ET-1-receptor blockers
      was more effective than either agent alone. We conclude that in CHF, circulating
      ANG II and ET-1 increase to very high levels during Ex and exacerbate the
      diastolic dysfunction present at rest.

PMID- 11247802
TI  - TNF-alpha induces protein synthesis through PI3-kinase-Akt/PKB pathway in cardiac
      myocytes.
AB  - The activation of phosphatidylinositol (PI) 3-kinase and Akt/protein kinase B
      (PKB) by tumor necrosis factor (TNF)-alpha and their roles on stimulation of
      protein synthesis were investigated in cultured neonatal rat cardiac myocytes.
      Treatment of cells with TNF-alpha resulted in enlargement of cell surface area
      and stimulation of protein synthesis without affecting myocyte viability. TNF
      alpha induced marked activation of PI3-kinase and Akt/PKB, and the activation of
      PI3-kinase and Akt/PKB was rapid (maximal at 10 and 15 min, respectively) and
      concentration dependent. Akt/PKB activation by TNF-alpha was inhibited by a PI3
      kinase-specific inhibitor LY-294002 and adenovirus-mediated expression of a
      dominant negative mutant of PI3-kinase, indicating that TNF-alpha activates
      Akt/PKB through PI3-kinase activation. Furthermore, TNF-alpha-induced protein
      synthesis was inhibited by pretreatment with LY-294002 and expression of a
      dominant negative mutant of PI3-kinase or Akt/PKB. These results indicate that
      activation of the PI3-kinase-Akt/PKB pathway plays an essential role in protein
      synthesis induced by TNF-alpha in cardiac myocytes.

PMID- 11247803
TI  - Regulation of Na(+) pump expression by vascular smooth muscle cells.
AB  - The Na(+) pump and its regulation is important for maintaining membrane potential
      and transmembrane Na(+) gradient in all mammalian cells and thus is essential for
      cell survival and function. Vascular smooth muscle cells (VSMC) have a relatively
      low number of pump sites on their membrane compared with other cells. We wished
      to determine the mechanisms for regulating the number of pump sites in these
      cells. We used canine saphenous vein VSMC cultured in 10% serum and passaged one
      time. These cells were subcultured in 5% serum media with low K(+) (1 mM vs.
      control of 5 mM), and their pump expression was assessed. These VSMC upregulated
      their pump sites as early as 4 h after treatment (measured by [(3)H]ouabain
      binding). At this early time point, there was no detectable increase in protein
      expression of either alpha(1)- or beta(1)-subunits of the pump shown by Western
      blots. When the cells were treated with the phosphoinositide 3-kinase (PI-3-K)
      inhibitor LY-294002 (which is known to inhibit cytoplasmic transport processes)
      in low-K(+) media, the pump site upregulation was inhibited. These data suggest
      that the low-K(+)-induced upregulation of Na(+) pump number can occur by
      translocation of preformed pumps from intracellular stores.

PMID- 11247804
TI  - Helium inhalation enhances vasodilator effect of inhaled nitric oxide on
      pulmonary vessels in hypoxic dogs.
AB  - There are theoretical and experimental indications that the presence of He as a
      balance gas markedly increase the diffusion velocity of other gases contained in
      a gas mixture. We allowed dogs with pulmonary vasoconstriction induced by hypoxia
      to inhale a mixture of 5 parts per million (ppm) of nitric oxide (NO) and O(2)
      balanced with He (NO in He) instead of N(2) (NO in N(2)). The dilating effect of
      NO in He and NO in N(2) on the pulmonary artery was evaluated by determining
      conventional pulmonary hemodynamic parameters, mean pulmonary artery (PA)
      pressure (MPAP), and pulmonary vascular resistance indexed to body surface area
      (PVRI), pulmonary impedance (Z), and the recently developed hemodynamic index,
      time-corrected wave intensity (WI). The main findings in this study were as
      follows: 1) hypoxia increased MPAP, PVRI, Z at 0 Hz (Z(0)), Z at the first
      harmonics, characteristic impedance (Z(c)), the reflection coefficient (Gamma),
      and the first peak of WI; 2) NO in N(2) reduced Z(0) and Gamma; and 3) NO in He
      reduced the first peak of WI and reduced Z(0) and Gamma more than NO in N(2). The
      enhanced vasodilatory effect of NO in He might be associated with facilitated
      diffusion of NO diluted in the gas mixture with He. In conclusion, increased
      efficacy of NO in He offers the possibility to reduce the inhaled NO
      concentration.

PMID- 11247806
TI  - Optical mapping of activation patterns in an animal model of congenital heart
      block.
AB  - Congenital heart block (CHB) is associated with high mortality and affects
      children of mothers with autoantibodies (IgG) to ribonucleoproteins SSB/La and
      SSA/Ro. IgG from mothers of children with CHB (positive IgG) was used to assess
      activation patterns in both the right atrium (RA) and right ventricle (RV) of
      Langendorff-perfused young rabbit hearts. Optical action potentials (AP) were
      obtained by using a 124-site photodiode array with 4-[-[2-(di-n-butylamino)-6
      naphthyl]vinyl]pyridinium. Optical APs were recorded to simultaneously image
      activation patterns from the RA and RV. Perfusion of positive IgG (800--1,200
      micro resulted in sinus bradycardia and varying degrees of heart block.
      Activation maps revealed marked conduction delay at the sinoatrial junction but
      only minor changes in overall atrial and ventricular activation patterns. No
      conduction disturbances were seen in the presence of IgG from mothers with
      healthy children. In conclusion, besides atrioventricular (AV) block, positive
      IgG induces sinus bradycardia. These results establish that the sequelae of CHB
      are associated with impaired intrasinus and/or sinoatrial conduction. The
      findings raise the possibility that sinus bradycardia in the developing heart may
      indicate the potential for AV conduction disturbances.

PMID- 11247805
TI  - ATP consumption by uncoupled mitochondria activates sarcolemmal K(ATP) channels
      in cardiac myocytes.
AB  - We tested whether close coupling exists between mitochondria and sarcolemma by
      monitoring whole cell ATP-sensitive K(+) (K(ATP)) current (I(K,ATP)) as an index
      of subsarcolemmal energy state during mitochondrial perturbation. In rabbit
      ventricular myocytes, either pinacidil or the mitochondrial uncoupler
      dinitrophenol (DNP), which rapidly switches mitochondria from net ATP synthesis
      to net ATP hydrolysis, had little immediate effect on I(K,ATP). In contrast, in
      the presence of pinacidil, exposure to 100 microM DNP rapidly activated I(K,ATP)
      with complex kinetics consisting of a quick rise [time constant of I(K,ATP)
      increase (tau) = 0.13 +/- 0.01 min], an early partial recovery (tau = 0.43 +/-
      0.04 min), and then a more gradual increase. This DNP-induced activation of
      I(K,ATP) was reversible and accompanied by mitochondrial flavoprotein oxidation.
      The F(1)F(0)-ATPase inhibitor oligomycin abolished the DNP-induced activation of
      I(K,ATP). The initial rapid rise in I(K,ATP) was blunted by atractyloside (an
      adenine nucleotide translocator inhibitor), leaving only a slow increase (tau =
      0.66 +/- 0.17 min, P < 0.01). 2,4-Dinitrofluorobenzene (a creatine kinase
      inhibitor) slowed both the rapid rise (tau = 0.20 +/- 0.01 min, P < 0.05) and the
      subsequent declining phase (tau = 0.88 +/- 0.19 min, P < 0.05). From single
      K(ATP) channel recordings, we excluded a direct effect of DNP on K(ATP) channels.
      Taken together, these results indicate that rapid changes in F(1)F(0)-ATPase
      function dramatically alter subsarcolemmal energy charge, as reported by
      pinacidil-primed K(ATP) channel activity, revealing cross-talk between
      mitochondria and sarcolemma. The effects of mitochondrial ATP hydrolysis on
      sarcolemmal K(ATP) channels can be rationalized by reversal of F(1)F(0)-ATPase
      and the facilitation of coupling by the creatine kinase system.

PMID- 11247807
TI  - Mechanism of reversible (99m)Tc-sestamibi perfusion defects during
      pharmacologically induced vasodilatation.
AB  - Reversible perfusion defects on (99m)Tc-sestamibi imaging during hyperemia are
      thought to occur due to myocardial blood flow (MBF) "mismatch" between regions
      with and without stenosis. We have recently shown that myocardial blood volume
      (MBV) distal to a stenosis decreases during hyperemia, resulting in a reversible
      perfusion defect on myocardial contrast echocardiography (MCE). In this study, we
      hypothesized that a reversible perfusion defect on (99m)Tc-sestamibi imaging
      during hyperemia results from the same mechanism. We tested our hypothesis under
      the following conditions: 1) increases in MBF in the absence of changes in MBV by
      using direct intracoronary infusion of adenosine (group I, n = 10 dogs); 2)
      decrease in MBV despite an increase in MBF by left main infusion of adenosine
      proximal to a noncritical coronary stenosis placed on either coronary artery
      (group II, n = 13 dogs); and 3) reduction in both resting MBF and MBV by
      placement of a severe stenosis (group III, n = 7 dogs). In group I dogs, no
      difference in MBV or (99m)Tc-sestamibi uptake was found between the two coronary
      beds despite an up to fourfold increase in MBF in one bed with adenosine. In
      group II dogs, MBV distal to the stenosis decreased during hyperemia despite a
      twofold increase in mean MBF. A good correlation was found between (99m)Tc
      sestamibi uptake and MBV ratios from the stenosed versus normal bed (r = 0.91, P
      < 0.001). In group III dogs, both MBF and MBV were decreased in the stenosed bed
      at rest with a good correlation noted between (99m)Tc-sestamibi uptake and MBV
      ratios from the stenosed versus normal bed (r = 0.92, P = 0.004). We conclude
      that reversible defects on (99m)Tc-sestamibi during vasodilator stress imaging
      are related to decreases in MBV distal to a stenosis and not to "flow mismatch"
      between beds. The decrease in MBV results in reduced (99m)Tc-sestamibi uptake
      during hyperemia.

PMID- 11247810
TI  - Sites of respiratory rhythmogenesis during development in the tadpole.
AB  - During ontogeny, amphibian larvae experience a dramatic alteration in the motor
      act of breathing as the premetamorphic gill breather develops into the
      postmetamorphic lung ventilator. We tested the hypothesis that the site of lung
      rhythmogenesis relocates during metamorphosis by recording fictive lung
      ventilation before and after transecting the in vitro brain stem of pre- and
      postmetamorphic Rana catesbeiana into four segments. In premetamorphic tadpoles,
      the two caudalmost brain stem segments combined proved to be the minimum brain
      stem configuration necessary and sufficient for lung burst generation. In the
      postmetamorphic counterpart, this function was supplied by the combination of the
      two rostralmost brain stem segments. In the postmetamorphic brain stem, a 500
      microm segment lying just rostral to cranial nerve IX conveys rhythmogenic
      capability to neighboring rostral or caudal segments. We conclude that lung
      rhythmogenic capability translocates rostrally during development as the tadpole
      shifts from gill to lung ventilation.

PMID- 11247811
TI  - Location of central respiratory chemoreceptors in the developing tadpole.
AB  - The location of central respiratory chemoreceptors in amphibian larvae may change
      as the central chemoreceptive function shifts from driving gill to driving lung
      ventilation during metamorphosis. We examined this possibility in the in vitro
      brain stem of the pre- and postmetamorphic Rana catesbeiana tadpole by
      microinjecting hypercapnic artificial cerebrospinal fluid (aCSF) while recording
      fictive lung ventilation. The rostral and caudal brain stem were separately
      explored systematically using injections of 11 nl of aCSF equilibrated with 100%
      CO2 that transiently acidified a 500-microm region, producing a maximum reduction
      in pH of 0.23 +/- 0.06 at the site of injection. In postmetamorphic tadpoles,
      chemoreceptive sites were concentrated in the rostral compared with the caudal
      brain stem. No such segregation was observed in the premetamorphic tadpole. We
      conclude that, as in lung rhythmogenic function, respiratory chemosensitivity
      emerges rostrally in the amphibian brain stem during development.

PMID- 11247809
TI  - Changes in cardiac contractile function and myocardial.
AB  - Cutaneous burn trauma causes cardiac contraction and relaxation defects, but the
      mechanism is unclear. Previous studies suggest that burn-related changes in
      myocyte handling of calcium may play an important role in postburn cardiac
      dysfunction. With the use of a high dissociation constant (K(d)) calcium
      indicator 1,2-bis(2-amino-5,6-difluorophenoxy)-ethane-N,N,N',N'-tetraacetic acid
      (TF-BAPTA) and (19)F NMR spectroscopy, this study examined the correlation
      between the changes in cytosolic free calcium concentration ([Ca(2+)](i)) and
      cardiac function after burn trauma. Sprague-Dawley rats were given scald burn
      (over 40% of the total body surface area) or sham burn. Twenty-four hours later,
      the hearts were excised and perfused by the Langendorff method with a modified
      phosphate-free Krebs-Henseleit bicarbonate buffer. Left ventricular (LV)
      developed pressure (LVDP), calculated from peak systolic LV pressure and LV end
      diastolic pressure, was assessed through a catheter attached to an
      intraventricular balloon. At the same time, (31)P and (19)F NMR spectroscopy was
      performed before and after TF-BAPTA loading. LVDP measured in hearts from burned
      rats was <40% than that measured in hearts from sham burn rats (65 +/- 6 vs. 110
      +/- 12 mmHg, P < 0.01); [Ca(2+)](i) was increased fourfold in hearts from the
      burned group compared with that measured in the sham burn group (0.807 +/- 0.192
      vs. 3.891 +/- 0.929 microM). Loading TF-BAPTA in hearts transiently decreased
      LVDP by 15%. Phosphocreatine-to-P(i) ratio decreased, but ATP and intracellular
      pH remained unchanged by either TF-BAPTA loading or burn trauma. In conclusion,
      burn trauma impaired cardiac contractility, and this functional defect was
      paralleled by a significant rise in [Ca(2+)](i) in the heart.

PMID- 11247808
TI  - Localized injury in cardiomyocyte network: a new experimental model of ischemia
      reperfusion arrhythmias.
AB  - We developed a new experimental approach to study the effects of local injury in
      a multicellular preparation and tested the ability of the method to induce
      reperfusion arrhythmias in cardiomyocyte monolayers. A small region of injury was
      created using geometrically defined flows of control and ischemia-like solutions.
      Calcium transients were acquired simultaneously from injured, control, and border
      zone cells using fluo 4. Superfusion with the injury solution rapidly diminished
      the amplitude of calcium transients within the injury zone, followed by cessation
      of cell beating. Reperfusion caused an immediate tachyarrhythmic response in
      approximately 17% of experiments, with a wave front propagating from a single
      cell or small cell cluster within the former injury zone. Inclusion of a gap
      junction uncoupler (1 mM heptanol) in the injury solution narrowed the functional
      border and sharply increased the number of ectopic foci and the incidence of
      reperfusion arrhythmias. The model holds a potential to reveal both micro- and
      macroscopic features of propagation, conduction, and cell coupling in the normal
      and diseased myocardium and to serve as a new tool to test antiarrhythmic
      protocols in vitro.

PMID- 11247812
TI  - The contribution of the vagus nerve in interleukin-1beta-induced fever is
      dependent on dose.
AB  - It has been suggested that proinflammatory cytokines communicate to the brain via
      a neural pathway involving activation of vagal afferents by interleukin-1beta (IL
      1beta), in addition to blood-borne routes. In support, subdiaphragmatic vagotomy
      blocks IL-1beta-induced, brain-mediated responses such as fever. However,
      vagotomy has also been reported to be ineffective. Neural signaling would be
      expected to be especially important at low doses of cytokine, when local actions
      could occur, but only very small quantities of cytokine would become systemic.
      Here, we examined core body temperature after intraperitoneal injections of three
      doses of recombinat human IL-1beta (rh-IL-1beta). Subdiaphragmatic vagotomy
      completely blocked the fever produced by 0.1 microg/kg, only partially blocked
      the fever produced by 0.5 microg/kg, and had no effect at all on the fever that
      followed 1.0 microg/kg rh-IL-1beta. Blood levels of rh-IL-1beta did not become
      greater than normal basal levels of endogenous rat IL-beta until the 0.5
      microg/kg dose nor was IL-1beta induced in the pituitary until this dose. These
      results suggest that low doses of intraperitoneal IL-1beta induce fever via a
      vagal route and that dose may account for some of the discrepancies in the
      literature.

PMID- 11247813
TI  - GRK3 mediates desensitization of CRF1 receptors: a potential mechanism regulating
      stress adaptation.
AB  - Potential G protein-coupled receptor kinase (GRK) and protein kinase A (PKA)
      mediation of homologous desensitization of corticotropin-releasing factor type 1
      (CRF1) receptors was investigated in human retinoblastoma Y-79 cells. Inhibition
      of PKA activity by PKI(5-22) or H-89 failed to attenuate homologous
      desensitization of CRF1 receptors, and direct activation of PKA by forskolin or
      dibutyryl cAMP failed to desensitize CRF-induced cAMP accumulation. However,
      treatment of permeabilized Y-79 cells with heparin, a nonselective GRK inhibitor,
      reduced homologous desensitization of CRF1 receptors by approximately 35%.
      Furthermore, Y-79 cell uptake of a GRK3 antisense oligonucleotide (ODN), but not
      of a random or mismatched ODN, reduced GRK3 mRNA expression by approximately 50%
      without altering GRK2 mRNA expression and inhibited homologous desensitization of
      CRF1 receptors by approximately 55%. Finally, Y-79 cells transfected with a GRK3
      antisense cDNA construct exhibited an approximately 50% reduction in GRK3 protein
      expression and an ~65% reduction in homologous desensitization of CRF1 receptors.
      We conclude that GRK3 contributes importantly to the homologous desensitization
      of CRF1 receptors in Y-79 cells, a brain-derived cell line.

PMID- 11247814
TI  - Mechanisms of blood pressure regulation that differ in men repeatedly exposed to
      high-G acceleration.
AB  - The purpose of this study was to test the hypothesis that repeated exposure to
      high acceleration (G) would be associated with enhanced functions of specific
      mechanisms of blood pressure regulation. We measured heart rate (HR), stroke
      volume (SV), cardiac output (), mean arterial blood pressure, central venous
      pressure, forearm and leg vascular resistance, catecholamines, and changes in leg
      volume (%DeltaLV) during various protocols of lower body negative pressure
      (LBNP), carotid stimulation, and infusions of adrenoreceptor agonists in 10 males
      after three training sessions on different days over a period of 5-7 days using a
      human centrifuge (G trained). These responses were compared with the same
      measurements in 10 males who were matched for height, weight, and fitness but did
      not undergo G training (controls). Compared with the control group, G-trained
      subjects demonstrated greater R-R interval response to equal carotid baroreceptor
      stimulation (7.3 +/- 1.2 vs. 3.9 +/- 0.4 ms/mmHg, P = 0.02), less
      vasoconstriction to equal low-pressure baroreceptor stimulation (-1.4 +/- 0.2 vs.
      -2.6 +/- 0.3 U/mmHg, P = 0.01), and higher HR (-1.2 +/- 0.2 vs. -0.5 +/- 0.1
      beats. min(-1). mmHg(-1), P = 0.01) and alpha-adrenoreceptor response (32.8 +/-
      3.4 vs. 19.5 +/- 4.7 U/mmHg, P = 0.04) to equal dose of phenylephrine. During
      graded LBNP, G-trained subjects had less decline in and SV, %DeltaLV, and
      elevation in thoracic impedance. G-trained subjects also had greater total blood
      (6,497 +/- 496 vs. 5,438 +/- 228 ml, P = 0.07) and erythrocyte (3,110 +/- 364 vs.
      2,310 +/- 96 ml, P = 0.06) volumes. These results support the hypothesis that
      exposure to repeated high G is associated with increased capacities of mechanisms
      that underlie blood pressure regulation.

PMID- 11247815
TI  - Nitric oxide increases fluid extravasation from the splenic circulation of the
      rat.
AB  - We hypothesized that nitric oxide (NO) contributes to intrasplenic fluid
      extravasation by inducing greater relaxation in splenic resistance arteries than
      veins such that intrasplenic microvascular pressure (P(C)) rises. Fluid efflux
      was estimated by measuring the difference between splenic blood inflow and
      outflow. Intrasplenic infusion of the NO donor S-nitroso-N-acetylpenicillamine
      (SNAP) (0.3 microg. 10 microl(-1). min(-1)) caused a significant increase in
      intrasplenic fluid efflux (baseline: 0.8 +/- 0.4 ml/min, n = 10 vs. peak rise
      during SNAP infusion: 1.3 +/- 0.4 ml/min, n = 10; P < 0.05). Intrasplenic P(C)
      was measured in the isolated, blood-perfused rat spleen. Intrasplenic infusion of
      SNAP (0.1 microg. 10 microl(-1). min(-1)) caused a significant increase in P(C)
      (saline: 10.9 +/- 0.2 mmHg, n = 3 vs. SNAP: 12.2 +/- 0.2 mmHg, n = 3; P < 0.05).
      Vasoreactivity of preconstricted splenic resistance vessels to sodium
      nitroprusside (SNP) (1 x 10(-12)-1 x 10(-4) M) and SNAP (1 x 10(-10)-3 x 10(-4)
      M) was investigated with the use of a wire myograph system. Significantly greater
      relaxation of arterioles than of venules occurred with both SNP (%maximal
      vasorelaxation: artery 96 +/- 2.3, n = 9 vs. vein 26 +/- 1.9, n = 10) and SNAP
      (%maximal vasorelaxation: artery 50 +/- 3.5, n = 11 vs. vein 32 +/- 1.7, n = 8).
      These results are consistent with our proposal that differential vasoreactivity
      of splenic resistance arteries and veins to NO elevates intrasplenic P(C) and
      increases fluid extravasation into the systemic lymphatic system.

PMID- 11247816
TI  - Expression of myogenic constrictor tone in the aorta of hypertensive rats.
AB  - We investigated the effect of intraluminal pressure or stretch on the development
      of tone in the descending thoracic aorta from rats with aortic coarctation
      induced hypertension of 7-14 days duration. Increments of pressure >100 mmHg
      decreased the diameter of thoracic aortas from hypertensive but not from
      normotensive rats. The pressure-induced constriction was not demonstrable in
      vessels superfused with calcium-free buffer. Stretched rings of aorta from
      hypertensive rats exhibited a calcium-dependent constrictor tone accompanied by
      elevated calcium influx that varied in relation to the degree of stretch.
      Blockers of L-type calcium channels and inhibitors of protein kinase C reduced
      both basal tone and calcium influx in aortic rings of hypertensive rats. Hence,
      the thoracic aorta of hypertensive rats expresses a pressure- and stretch
      activated constrictor mechanism that relies on increased calcium influx through L
      type calcium channels via a protein kinase C-regulated pathway. The expression of
      such a constrictor mechanism is suggestive of acquired myogenic behavior.

PMID- 11247817
TI  - Sympathoinhibition from ventrolateral periaqueductal gray mediated by 5-HT(1A)
      receptors in the RVLM.
AB  - The role of 5-hydroxytryptamine 1A (5-HT(1A)) receptors located in the rostral
      ventrolateral medulla (RVLM) in the mediation of a sympathoinhibitory and
      depressor response elicited from the ventrolateral periaqueductal gray (vlPAG)
      matter of the midbrain was examined in pentobarbital sodium-anesthetized rats.
      Activation of neurons in the vlPAG evoked a decrease in renal and lumbar
      sympathetic nerve activities and a decrease in arterial blood pressure. After
      microinjection of the specific 5-HT(1A)-receptor antagonist WAY-100635 into the
      pressor area of the RVLM, the vlPAG-evoked sympathoinhibition and hypotension was
      attenuated to control levels (7 of 15 animals) or converted into a
      sympathoexcitation and pressor response (8 of 15 animals). Baroreflex inhibition
      of sympathetic nerve activity was not impaired by microinjection of WAY into the
      sympathoexcitatory region of the RVLM. These data suggest that sympathoinhibition
      and hypotension elicited by activation of neurons in the vlPAG are mediated by 5
      HT(1A) receptors in the RVLM.

PMID- 11247818
TI  - Defense reaction alters the response to blood loss in the conscious rabbit.
AB  - The interaction of sensory stressors with the cardiovascular response to blood
      loss has not been studied. The cardiovascular response to a stressor (i.e., the
      defense reaction) includes increased skeletal muscle blood flow and perhaps a
      reduction in arterial baroreflex function. Arterial pressure maintenance during
      blood loss requires baroreflex-mediated skeletal muscle vasoconstriction.
      Therefore, we hypothesized that the defense reaction would limit arterial
      pressure maintenance during blood loss. Male, New Zealand White rabbits were
      chronically prepared with arterial and venous catheters and Doppler flow probes.
      We removed venous blood in conscious rabbits until mean arterial pressure
      decreased to <40 mmHg. We repeated the experiment with (air) and without (sham)
      simultaneous exposure to an air jet stressor. Air resulted in a defense reaction
      (e.g., mean arterial pressure = 94 +/- 1 and 67 +/- 1 mmHg for air and sham,
      respectively). Contrary to our hypothesis, air increased the blood loss necessary
      to produce hypotension (19.3 +/- 0.2 vs. 16.9 +/- 0.2 ml/kg for sham). Air did
      not reduce skeletal muscle vasoconstriction during normotensive hemorrhage.
      However, air did enhance renal vasoconstriction (97 +/- 3 and 59 +/- 3% of
      baseline for sham and air, respectively) during the normotensive phase. Thus the
      defense reaction did not limit but rather extended defense of arterial pressure
      during hemorrhage.

PMID- 11247819
TI  - Mechanisms of angiotensin-(1-7)-induced inhibition of angiogenesis.
AB  - Angiotensin-(1-7) [ANG-(1-7)], an endogenous bioactive peptide constituent of the
      renin-angiotensin system, acts as an inhibitory growth factor in vitro and in
      vivo. In this study, we evaluated whether the antiangiogenic effect of ANG-(1-7)
      in the mouse sponge model of angiogenesis might be receptor mediated and involved
      in the release of nitric oxide (NO). The hemoglobin content (microg/mg wet
      tissue) of 7-day-old sponge implants was used as an index of the vascularization
      and showed that daily injections of ANG-(1-7) (20 ng) inhibited significantly the
      angiogenesis in the implants relative to the saline-treated group. The specific
      receptor antagonist D-Ala(7)-ANG-(1-7); A-779 prevented ANG-(1-7)-induced
      inhibition of angiogenesis. The antiangiogenic effect was also abolished by
      pretreatment with NO synthase inhibitors aminoguanidine (1 mg/ml) or N(G)-nitro-L
      arginine methyl ester (0.3 mg/ml). Selective AT1 and AT2 angiotensin-receptor
      antagonists and an angiotensin-converting enzyme inhibitor, in combination with
      ANG-(1-7) or alone, did not alter angiogenesis in the implants. These results
      establish that the regulation of the vascular tissue growth by ANG-(1-7) is
      associated with NO release by activation of an angiotensin receptor distinct from
      AT1 and AT2.

PMID- 11247820
TI  - Glial cell line-derived neurotrophic factor promotes sleep in rats and rabbits.
AB  - Various growth factors (e.g., growth hormone-releasing hormone, acidic fibroblast
      growth factor, nerve growth factor, brain-derived neurotrophic factor, and
      interleukin-1) are implicated in sleep regulation. It is hypothesized that
      neuronal activity enhances the production of such growth factors, and they in
      turn form part of the sleep regulatory mechanism. Glial cell line-derived
      neurotrophic factor (GDNF) promotes development, differentiation, maintenance,
      and regeneration of neurons, and its production is induced by well-characterized
      sleep regulatory substances such as interleukin-1 and tumor necrosis factor.
      Therefore, we investigated whether GDNF would promote sleep. Twenty-six male
      Sprague-Dawley rats and 30 male New Zealand White rabbits were surgically
      implanted with electroencephalogram (EEG) and electromyogram (EMG; rats only)
      electrodes, a brain thermistor, and a lateral intracerebroventricular cannula.
      The animals were injected intracerebroventricularly with pyrogen-free saline and
      on a separate day with one of the following doses of GDNF: 5, 50, and 500 ng in
      rabbits and 50 and 500 ng in rats. The EEG, brain temperature, EMG (in rats), and
      motor activity (in rabbits) were recorded for 23 h after the
      intracerebroventricular injection. GDNF (500-ng dose) increased the time spent in
      nonrapid eye movement sleep in both rats and rabbits. Rapid eye movement sleep
      was not affected by the lower doses of GDNF but was inhibited in rabbits after
      the high dose. EEG slow-wave activity was not affected by GDNF. The current
      results provide further evidence that various growth factors are involved in
      sleep regulation.

PMID- 11247821
TI  - Cardiovascular and metabolic responses to fasting and thermoneutrality are
      conserved in obese Zucker rats.
AB  - The primary purpose of the study was to test the hypothesis that reduced leptin
      signaling is necessary to elicit the cardiovascular and metabolic responses to
      fasting. Lean (Fa/?; normal leptin receptor; n = 7) and obese (fa/fa; mutated
      leptin receptor; n = 8) Zucker rats were instrumented with telemetry transmitters
      and housed in metabolic chambers at 23 degrees C (12:12-h light-dark cycle) for
      continuous (24 h) measurement of metabolic and cardiovascular variables. Before
      fasting, mean arterial pressure (MAP) was higher (MAP: obese = 103 +/- 3; lean =
      94 +/- 1 mmHg), whereas oxygen consumption (VO(2): obese = 16.5 +/- 0.3; lean =
      18.6 +/- 0.2 ml. min(-1). kg(-0.75)) was lower in obese Zucker rats compared with
      their lean controls. Two days of fasting had no effect on MAP in either lean or
      obese Zucker rats, whereas VO(2) (obese = -3.1 +/- 0.3; lean = -2.9 +/- 0.1 ml.
      min(-1). kg(-0.75)) and heart rate (HR: obese = -56 +/- 4; lean = -42 +/- 4
      beats/min) were decreased markedly in both groups. Fasting increased HR
      variability both in lean (+1.8 +/- 0.4 ms) and obese (+2.6 +/- 0.3 ms) Zucker
      rats. After a 6-day period of ad libitum refeeding, when all parameters had
      returned to near baseline levels, the cardiovascular and metabolic responses to 2
      days of thermoneutrality (ambient temperature 29 degrees C) were determined.
      Thermoneutrality reduced VO(2) (obese = -2.4 +/- 0.2; lean = -3.3 +/- 0.2 ml.
      min(-1). kg(-0.75)), HR (obese = -46 +/- 5; lean = -55 +/- 4 beats/min), and MAP
      (obese = -13 +/- 6; lean = -10 +/- 1 mmHg) similarly in lean and obese Zucker
      rats. The results indicate that the cardiovascular and metabolic responses to
      fasting and thermoneutrality are conserved in Zucker rats and suggest that intact
      leptin signaling may not be requisite for the metabolic and cardiovascular
      responses to reduced energy intake.

PMID- 11247823
TI  - Functioning of the rat circadian system is modified by light applied in critical
      postnatal days.
AB  - Lighting conditions influence biological clocks. The present experiment was
      designed to test the presence of a critical window of days during the lactation
      stage of the rat in which light has a decisive role on the development of the
      circadian system. Rats were exposed to 4, 8, or 12 days of constant light (LL)
      during the first days of life. Their circadian rhythm was later studied under LL
      and constant darkness. The response to a light pulse was also examined. Results
      show that the greater the number of LL days during lactation, the stronger the
      rhythm under LL and the smaller the phase shift due to the light pulse. These
      responses are enhanced when rats are exposed to LL days around postnatal day 12.
      A mathematical model was built to explain the responses of the circadian system
      with respect to the timing of LL during lactation, and we deduced that between
      postnatal days 10 to 20 there is a critical period of sensitivity to light;
      consequently, exposure to LL during this time modifies the circadian organization
      of the motor activity.

PMID- 11247822
TI  - NO supports right ventricular flow dominance and whole body O(2) utilization in
      midgestation fetal lambs.
AB  - It is unknown if nitric oxide (NO) modulates the relative levels of left (LV) and
      right (RV) ventricular output, fetal O2 consumption, or blood flow distribution
      between the body and placenta at midgestation. To address these questions, six
      fetal lambs were instrumented at 89-96 days gestation (term 147 days), and blood
      flows were measured with radioactive microspheres 3-4 days later at baseline and
      after inhibition of NO synthesis with 10 mg/kg (L-NNA10) and 25 mg/kg (L-NNA25)
      N(omega)-nitro-L-arginine. LV output fell by 74 +/- 15 ml. min(-1). kg(-1) at L
      NNA10 (P < 0.005), whereas RV output decreased by 90 +/- 18 ml. min(-1). kg(-1)
      at L-NNA10 (P < 0.02) and by a further 80 +/- 22 ml. min(-1). kg(-1) at L-NNA25
      (P < 0.05). As a result, RV output exceeded LV output at baseline (P = 0.03) and
      L-NNA10 (P < 0.02) but not at L-NNA25. Fetal body blood flow fell by 95 +/- 25
      ml. min(-1). kg(-1) at L-NNA10 (P < 0.01), but because placental blood flow
      decreased by 70 +/- 22 ml. min(-1). kg(-1) at L-NNA10 (P < 0.01) and a further 71
      +/- 21 ml. min(-1). kg(-1) at L-NNA25 (P < 0.01), the fetal body-to-placental
      blood flow ratio was near unity at baseline and L-NNA10 but rose to 1.5 +/- 0.3
      at L-NNA25 (P < 0.05). In association with these flow changes, fetal O2
      consumption declined by 1.4 +/- 0.3 ml. min(-1). kg(-1) at L-NNA10 (P < 0.05) and
      by a further 1.5 +/- 0.6 ml. min(-1). kg(-1) at L-NNA25 (P < 0.02). These
      findings suggest that, in midgestation fetal lambs, NO supports an RV flow
      dominance, whole body O2 utilization, and the maintenance of a near-equal
      fetoplacental blood flow distribution.

PMID- 11247825
TI  - Fcgamma-receptor signaling augments the LPS-stimulated increase in serum tumor
      necrosis factor-alpha levels.
AB  - The phagocytosis of IgG-coated erythrocytes (EIgG) has been shown to augment the
      bacterial lipopolysaccharide (LPS)-stimulated increase in serum tumor necrosis
      factor-alpha (TNF-alpha) levels. The present study evaluated the role of Fcgamma
      receptor (FcgammaR) signaling and complement activation in the effect of EIgG on
      the TNF-alpha response to LPS. The role of FcgammaR was determined using FcR
      gamma-chain knockout mice that lack functional FcgammaRI and FcgammaRIII. In wild
      type animals, EIgG caused a 16-fold augmentation of the serum TNF-alpha response
      to LPS, whereas there was no augmentation in the FcgammaR-deficient animals. Heat
      damaged erythrocytes also augmented the TNF-alpha response to LPS. This effect
      was absent in FcgammaR-deficient animals. An IgG antibody against heated
      erythrocytes was detected in mouse serum. The complement activation caused by
      EIgG had little effect on the LPS-stimulated increase in serum TNF-alpha levels
      as indicated by activation of complement with cobra venom factor or IgM-coated
      erythrocytes as well as studies with C5-deficient mice. These results indicate
      that FcgammaR signaling primarily mediates the augmented serum TNF-alpha response
      to LPS caused by EIgG.

PMID- 11247824
TI  - Increased heat-escape/cold-seeking behavior following hypertonic saline injection
      in rats.
AB  - We examined the effect of hypertonic saline injection on heat-escape/cold-seeking
      behavior in desalivated rats. Rats were exposed to 40 degrees C heat after normal
      (154 mM NaCl, control) or hypertonic saline (2,500 mM NaCl) injection (1 ml/100 g
      body wt). The rats received a 0 degrees C air for 30 s when they entered a
      specific area in an experimental box. Core temperature (T(c)) surpassed 40
      degrees C in both conditions when 0 degrees C air was not available. Hypertonic
      saline injection produced a lower baseline T(c) than control [36.9 +/- 0.2 and
      37.9 +/- 0.2 degrees C (means +/- SE), P < 0.05] and a greater number of 0
      degrees C air rewards during the 2-h heat with lower T(c) at the end (48 +/- 1
      and 34 +/- 2, 37.6 +/- 0.1, and 37.3 +/- 0.1 degrees C in the control and
      hypertonic saline injection trial, respectively, P < 0.05, n = 6). However, T(c)
      was similar (37.7 +/- 0.2 and 37.6 +/- 0.4 degrees C in the control and
      hypertonic saline injection trial, n = 5) when 0 degrees C air was automatically
      and intermittently (35 times) given during the heat. Rats augment heat-defense
      mechanisms in response to osmotic stress by lowering the baseline T(c) and
      increasing heat-escape/cold-seeking behavior.

PMID- 11247826
TI  - Nonimmune hydrops fetalis and activation of the renin-angiotensin system after
      asphyxia in preterm fetal sheep.
AB  - This study examined the hypothesis that the development of hydrops fetalis after
      asphyxia in the 0.6 gestation sheep fetus would be associated with activation of
      the fetal renin-angiotensin system (RAS). Fetuses were randomly assigned to
      either sham occlusion (n = 7) or to 30 min of asphyxia induced by complete
      umbilical cord occlusion for 30 min (n = 8). Asphyxia led to severe bradycardia
      and hypotension that resolved after release of occlusion. After occlusion, plasma
      renin concentration was significantly increased in the asphyxia group compared
      with controls (P < 0.005) after 3 min (16.3 +/- 5.3 vs. 4.1 +/- 1.3 ng. ml(-1).
      h(-1)), and 72 h (30.6 +/- 6.3 vs. 3.7 +/- 1.2 ng. ml(-1). h(-1)). Renal renin
      concentrations and mRNA levels were significantly greater in the asphyxia group
      after 72 h of recovery. All fetuses in the asphyxia group showed generalized
      tissue edema, ascites, and pleural effusions after 72 h of recovery. In
      conclusion, asphyxia in the preterm fetus caused sustained activation of the RAS,
      which was associated with hydrops fetalis.

PMID- 11247828
TI  - Neuropeptide Y inhibits estrous behavior and stimulates feeding via separate
      receptors in Syrian hamsters.
AB  - Central injections of neuropeptide Y (NPY) increase food intake in Syrian
      hamsters; however, the effect of NPY on sexual behavior in hamsters is not known
      nor are the receptor subtypes involved in feeding and sexual behaviors. We
      demonstrate that NPY inhibits lordosis duration in a dose-related fashion after
      lateral ventricular injection in ovariectomized, steroid-primed Syrian hamsters.
      Under the same conditions, we compared the effect of two receptor-differentiating
      agonists derived from peptide YY (PYY), PYY-(3-36) and [Leu(31),Pro(34)]PYY, on
      lordosis duration and food intake. PYY-(3-36) produced a 91% reduction in
      lordosis duration at 0.24 nmol. [Leu(31),Pro(34)]PYY was less potent, producing a
      reduction in lordosis duration (66%) only at 2.4 nmol. These results suggest NPY
      effects on estrous behavior are principally mediated by Y2 receptors. PYY-(3-36)
      and [Leu(31),Pro(34)]PYY stimulated comparable dose-related increases in total
      food intake (2 h), suggesting Y5 receptors are involved in feeding. The
      significance of different NPY receptor subtypes controlling estrous and feeding
      behavior is highlighted by results on expression of Fos immunoreactivity (Fos-IR)
      elicited by either PYY-(3-36) or [Leu(31),Pro(34)]PYY at a dose of each that
      differentiated between the two behaviors. Some differences were seen in the
      distribution of Fos-IR produced by the two peptides. Overall, however, the
      patterns of expression were similar. Our behavioral and anatomic results suggest
      that NPY-containing pathways controlling estrous and feeding behavior innervate
      similar nuclei, with the divergence in pathways controlling the separate
      behaviors characterized by linkage to different NPY receptor subtypes.

PMID- 11247827
TI  - Reduced feeding response to neuropeptide Y in senescent Fischer 344 rats.
AB  - The anorexia of aging syndrome in humans is characterized by spontaneous body
      weight loss reflecting diminished food intake. We reported previously that old
      rats undergoing a similar phenomenon of progressive weight loss (i.e., senescent
      rats) also display altered feeding behavior, including reduced meal size and
      duration. Here, we tested the hypothesis that blunted responsiveness to
      neuropeptide Y (NPY), a feeding stimulant, occurs concurrently with senescence
      associated anorexia/hypophagia. Young (8 mo old, n = 9) and old (24-30 mo old, n
      = 11) male Fischer 344 rats received intracerebroventricular NPY or artificial
      cerbrospinal fluid injections. In response to a maximum effective NPY dose (10
      microg), the net increase in size of the first meal after injection was similar
      in old weight-stable (presenescent) and young rats (10.85 +/- 1.73 and 12.63 +/-
      2.52 g/kg body wt (0.67), respectively). In contrast, senescent rats that had
      spontaneously lost approximately 10% of body weight had significantly lower net
      increases at their first post-NPY meal (1.33 +/- 0.33 g/kg body wt (0.67)) than
      before they began losing weight. Thus altered feeding responses to NPY occur in
      aging rats concomitantly with spontaneous decrements in food intake and body
      weight near the end of life.

PMID- 11247829
TI  - Effects of dietary salt intake on plasma arginine.
AB  - Because L-arginine is degraded by hepatic arginase to ornithine and urea and is
      transported by the regulated 2A cationic amino acid y(+) transporter (CAT2A),
      hepatic transport may regulate plasma arginine concentration. Groups of rats (n =
      6) were fed a diet of either low salt (LS) or high salt (HS) for 7 days to test
      the hypothesis that dietary salt intake regulates plasma arginine concentration
      and renal nitric oxide (NO) generation by measuring plasma arginine and ornithine
      concentrations, renal NO excretion, and expression of hepatic CAT2A, and
      arginase. LS rats had lower excretion of NO metabolites and cGMP, lower plasma
      arginine concentration (LS: 83 +/- 7 vs. HS: 165 +/- 10 micromol/l, P < 0.001),
      but higher plasma ornithine concentration (LS: 82 +/- 6 vs. HS: 66 +/- 4
      micromol/l, P < 0.05) and urea excretion. However, neither the in vitro hepatic
      arginase activity nor the mRNA for hepatic arginase I was different between
      groups. In contrast, LS rats had twice the abundance of mRNA for hepatic CAT2A
      (LS: 3.4 +/- 0.4 vs. HS: 1.6 +/- 0.5, P < 0.05). The reduced plasma arginine
      concentration with increased plasma ornithine concentration and urea excretion
      during LS indicates increased arginine metabolism by arginase. This cannot be
      ascribed to changes in hepatic arginase expression but may be a consequence of
      increased hepatic arginine uptake via CAT2A.

PMID- 11247830
TI  - Abnormal renal medullary response to angiotensin II in SHR is corrected by long
      term enalapril treatment.
AB  - This study tested the hypotheses that renal medullary blood flow (MBF) in
      spontaneously hypertensive rats (SHR) has enhanced responsiveness to angiotensin
      (ANG) II and that long-term treatment with enalapril can correct this. MBF,
      measured by laser Doppler flowmetry in anesthetized rats, was not altered
      significantly by ANG II in Wistar-Kyoto (WKY) rats, but was reduced dose
      dependently (25% at 50 ng. kg(-1). min(-1)) in SHR. Infusion of N(G)-nitro-L
      arginine methyl ester (L-NAME) into the renal medulla unmasked ANG II sensitivity
      in WKY rats while L-arginine given into the renal medulla abolished the responses
      to ANG II in SHR. In 18- to 19-wk-old SHR treated with enalapril (25 mg. kg(-1).
      day(-1) when 4 to 14 wk old), ANG II did not alter MBF significantly, but
      sensitivity to ANG II was unmasked after L-NAME was infused into the renal
      medulla. Endothelium-dependent vasodilation (assessed with aortic rings) was
      significantly greater in treated SHR when compared with that in control SHR.
      These results indicate that MBF in SHR is sensitive to low-dose ANG II and
      suggest that this effect may be due to an impaired counterregulatory effect of
      nitric oxide. Long-term treatment with enalapril improves endothelium-dependent
      vascular relaxation and decreases the sensitivity of MBF to ANG II. These effects
      may be causally related to the persistent antihypertensive action of enalapril in
      SHR.

PMID- 11247831
TI  - Muscimol infusions in the brain stem reticular formation reversibly block
      ingestion in the awake rat.
AB  - Previous studies have localized a central pattern generator for mastication to
      the midline pontomedullary reticular formation (RF) based on cortically induced
      ororhythmic movements. The present study determined whether this same substrate
      mediated licking responses evoked by more natural stimuli. Licking in the awake
      rat was initiated either through an appetitive response to sucrose presented in a
      bottle or by intraoral (IO) infusions. Oral rejection responses also were
      obtained by IO infusions of quinine hydrochloride. Small volumes of the GABA(A)
      agonist muscimol bilaterally infused into the lateral medullary RF significantly
      reduced licking and oral rejection responses measured electromyographically from
      the anterior digastric and geniohyoid muscles. Other than the decrement or
      absence of ororhythmic activity, rats appeared normal and actively approached and
      probed the water bottle. The suppression was reversible and returned to baseline
      within 3 h. In contrast, midline infusions of muscimol did not affect licking or
      rejection responses. We postulate that the lateral medullary RF is an essential
      final common path for ingestive consummatory responses.

PMID- 11247833
TI  - Slow oscillations in blood pressure via a nonlinear feedback model.
AB  - Blood pressure is well established to contain a potential oscillation between 0.1
      and 0.4 Hz, which is proposed to reflect resonant feedback in the baroreflex
      loop. A linear feedback model, comprising delay and lag terms for the
      vasculature, and a linear proportional derivative controller have been proposed
      to account for the 0.4-Hz oscillation in blood pressure in rats. However,
      although this model can produce oscillations at the required frequency, some
      strict relationships between the controller and vasculature parameters must be
      true for the oscillations to be stable. We developed a nonlinear model,
      containing an amplitude-limiting nonlinearity that allows for similar
      oscillations under a very mild set of assumptions. Models constructed from
      arterial pressure and sympathetic nerve activity recordings obtained from
      conscious rabbits under resting conditions suggest that the nonlinearity in the
      feedback loop is not contained within the vasculature, but rather is confined to
      the central nervous system. The advantage of the model is that it provides for
      sustained stable oscillations under a wide variety of situations even where gain
      at various points along the feedback loop may be altered, a situation that is not
      possible with a linear feedback model. Our model shows how variations in some of
      the nonlinearity characteristics can account for growth or decay in the
      oscillations and situations where the oscillations can disappear altogether. Such
      variations are shown to accord well with observed experimental data.
      Additionally, using a nonlinear feedback model, it is straightforward to show
      that the variation in frequency of the oscillations in blood pressure in rats
      (0.4 Hz), rabbits (0.3 Hz), and humans (0.1 Hz) is primarily due to scaling
      effects of conduction times between species.

PMID- 11247832
TI  - Effect of repetitive icv injections of ANG II on c-Fos and AT(1)-receptor
      expression in the rat brain.
AB  - ANG II has been implicated in neuroplastic processes via stimulation of inducible
      transcription factors (ITF) in the brain. In the present study, we investigated
      the effects of acute vs. repetitive once daily intracerebroventricular injections
      of ANG II for 7 days on the expression of ITF and constitutive transcription
      factor (CTF) and the AT1 receptor in the median preoptic area (MnPO), the
      subfornical organ (SFO), and the hypothalamic paraventricular (PVN) and
      supraoptic nuclei (SON). After repetitive injections, the expression of c-Fos
      declined by approximately 50% in MnPO, SFO, PVN, and SON compared with controls
      injected once. The desensitization of c-Fos occurred on the transcriptional level
      as shown in the SON by RT-PCR. Apart from a novel expression of c-Jun in the SON,
      the ITF c-Jun, JunB, JunD, and Krox-24 did not change after repetitive
      stimulation. Neither were the CTF, calcium response element binding protein,
      activating transcription factor 2, and serum response factor altered after
      repetitive vs. single injections of ANG II. The AT1 receptor was coexpressed with
      c-Fos/c-Jun. Immunohistochemical stainings suggest an increase in AT1-receptor
      number in MnPO, SFO, PVN, and SON on chronic stimulation compared with once
      injected controls. These findings demonstrate that repetitive periventricular
      stimulation with ANG II essentially alters the expression of transcription
      factors compared with acute stimulation and suggest c-Fos and c-Jun as major
      intermediates of the AT1-receptor transcription.

PMID- 11247834
TI  - The functional regeneration of syncytiotrophoblast in cultured explants of term
      placenta.
AB  - We have investigated the functional characteristics of term human placental
      villous explants kept in long-term (7-11 days) culture. Fragments of placental
      villous tissue (approximately 5-10 mg wet wt) were cultured in supplemented CMRL
      1066 culture medium for up to 11 days. After the first day of culture, the
      syncytiotrophoblast appeared vacuolated and eventually degenerated. However, a
      new syncytiotrophoblast developed by day 4, being indistinguishable from that of
      a fresh placenta by 11 days. Release of human chorionic gonadotrophin increased
      and activity of lactate dehydrogenase in culture medium decreased with culture
      time. Transport variables were measured over the first 7 days of culture. Basal
      (86)Rb efflux was reduced with time in culture and was inhibited by Ba2+,
      suggesting the efflux was mediated by K+ channels. At all stages of culture,
      (86)Rb efflux was stimulated by ATP, hyposmotic medium, and ANG II. A complex
      pattern of efflux changes with culture time and type of stimulator was observed,
      suggesting that several compartments of the tissue contributed to stimulated
      efflux. This culture system provides opportunities for studies of chronic
      regulation of placental function.

PMID- 11247836
TI  - Prenatal nicotine alters vigilance states and AchR gene expression in the
      neonatal rat: implications for SIDS.
AB  - Maternal smoking is a major risk factor for sudden infant death syndrome (SIDS).
      The mechanisms by which cigarette smoke predisposes infants to SIDS are not
      known. We examined the effects of prenatal nicotine exposure on sleep/wake
      ontogenesis and central cholinergic receptor gene expression in the neonatal rat.
      Prenatal nicotine exposure transiently increased sleep continuity and accelerated
      sleep/wake ontogeny in the neonatal rat. Prenatal nicotine also upregulated
      nicotinic and muscarinic cholinergic receptor mRNAs in brain regions involved in
      regulating vigilance states. These findings suggest that the nicotine contained
      in cigarette smoke may predispose human infants to SIDS by interfering with the
      normal maturation of sleep and wake.

PMID- 11247837
TI  - Parabrachial nucleus modulates cardiovascular responses to blood loss.
AB  - The goal of this study was to determine the role of the pontine lateral
      parabrachial nucleus (LPBN) in the compensatory responses to blood loss.
      Conscious unrestrained rats with complete, partial, or sham bilateral ibotenic
      acid lesions of the LPBN were subjected to a hypotensive 16-ml/kg blood
      withdrawal via arterial catheter. Complete lesions (LPBNx) encompassed the entire
      LPBN and extended into the ventrolateral parabrachial region to encroach on the
      Kolliker-Fuse nucleus. Partial lesions were restricted to the body of the LPBN
      and spared the outer rim of the external lateral subnucleus of the LPBN. In all
      three groups, serum corticosterone concentration and plasma renin activity
      increased four- to fivefold after hemorrhage (P < 0.01), and immunocytochemistry
      demonstrated numerous Fos-positive neurons in the hypothalamic supraoptic
      nucleus. However, the cardiovascular responses to hypotensive blood loss differed
      for complete and partial lesions. Blood pressure failed to recover in LPBNx rats
      and was significantly lower in LPBNx (66 +/- 4 mmHg) than in rats with partial or
      sham lesions (98 +/- 4 and 85 +/- 5 mmHg, respectively) at 40 min posthemorrhage.
      In contrast, rats with partial lesions had a significant attenuation of the
      posthemorrhage bradycardia. This implies that a population of neurons within the
      body of the LPBN is essential for full expression of the bradycardia that
      accompanies hemorrhagic hypotension, whereas the ventrolateral parabrachial
      region is essential for normal restoration of arterial pressure after hypotensive
      hemorrhage.

PMID- 11247835
TI  - Oxygen affinity and amino acid sequence of myoglobins from endothermic and
      ectothermic fish.
AB  - Myoglobin (Mb) buffers intracellular O2 and facilitates diffusion of O2 through
      the cell. These functions of Mb will be most effective when intracellular PO2 is
      near the partial pressure of oxygen at which Mb is half saturated (P50) of the
      molecule. We test the hypothesis that Mb oxygen affinity has evolved such that it
      is conserved when adjusted for body temperature among closely related animals. We
      measure oxygen P50s tonometrically and oxygen dissociation rate constants with
      stopped flow and generate amino acid sequence from cDNA of Mbs from fish with
      different body temperatures. P50s for the endothermic bluefin tuna, skipjack
      tuna, and blue marlin at 20 degrees C were 0.62 +/- 0.02, 0.59 +/- 0.01, 0.58 +/-
      0.04 mmHg, respectively, and were significantly lower than those for ectothermic
      bonito (1.03 +/- 0.07 mmHg) and mackerel (1.39 +/- 0.03 mmHg). Because the oxygen
      affinity of Mb decreases with increasing temperature, the above differences in
      oxygen affinity between endothermic and ectothermic fish are reduced when
      adjusted for the in vivo muscle temperature of the animal. Oxygen dissociation
      rate constants at 20 degrees C for the endothermic species ranged from 34.1 to
      49.3 s(-1), whereas those for mackerel and bonito were 102 and 62 s(-1),
      respectively. Correlated with the low oxygen affinity and fast dissociation
      kinetics of mackerel Mb is a substitution of alanine for proline that would
      likely result in a more flexible mackerel protein.

PMID- 11247838
TI  - Loxiglumide, a CCK-A receptor antagonist, stimulates calorie intake and hunger
      feelings in humans.
AB  - Exogenous cholecystokinin (CCK) induces early satiety when infused into humans.
      Whether alimentary CCK (CCK-A) receptor blockade stimulates food intake in humans
      is, however, uncertain. The aim of the present investigation was, therefore, to
      establish the effect of CCK-A receptor blockade on satiety and eating behavior in
      healthy volunteers. To further explore the role of endogenous CCK, the effects of
      the specific CCK-A receptor antagonist loxiglumide (Lox; 22 micromol. kg(-1). h(
      1)) on satiety and eating behavior were investigated in healthy men and compared
      with saline infusions (as placebo) in a series of randomized, double-blind,
      placebo-controlled, crossover studies. Lox produced a slight (7%), but not
      significant (P = 0.104), increase in food intake that was accompanied by a modest
      (10%), but significant (P < 0.004), increase in calorie intake. Fluid ingestion
      was not affected by Lox. Subjects experienced more hunger and delayed fullness
      during Lox infusion than during saline infusion (P < 0.05). This study provides
      further evidence that CCK is an endogenous physiological satiety signal acting
      through CCK-A receptor-mediated mechanisms. Repeated-dose studies comparing
      hunger and satiety responses after CCK-A receptor blockade in healthy subjects
      and patients with eating disorders may help clarify the possible involvement of
      endogenous CCK in these conditions.

PMID- 11247841
TI  - Lactation decreases angiotensinogen mRNA expression in the midcaudal arcuate
      nucleus of the rat brain.
AB  - In lactating rats, ANG II receptor binding in the arcuate nucleus (ARH) and
      median eminence is decreased. To further evaluate brain angiotensinergic activity
      during lactation, we assessed angiotensinogen (AON) mRNA by in situ hybridization
      in forebrains of day 10 or 11 postpartum lactating and diestrous rats. AON mRNA
      was abundantly expressed in the ARH, preoptic, suprachiasmatic, supraoptic,
      paraventricular, and dorsomedial hypothalamic nuclei, and other regions, similar
      to that reported in male rat brains. AON mRNA levels were decreased 27% in the
      midcaudal ARH of lactating rats but did not differ between lactating or diestrous
      rats in any of the other brain areas examined. Immunofluorescence for AON and
      glial fibrillary acidic protein or tyrosine hydroxylase confirmed that the AON
      immunoreactivity in the ARH was limited to astrocytes. Confocal microscopy
      revealed close appositions of AON-positive astrocytes to dopaminergic neurons in
      the ARH. The decrease in AON mRNA in the midcaudal ARH during lactation coupled
      with decreased ARH ANG II receptor binding suggests that lactating rats are less
      subject to ANG II-mediated inhibition of prolactin secretion.

PMID- 11247842
TI  - Enhanced central response to dehydration in mice lacking angiotensin AT(1a)
      receptors.
AB  - The objective was to determine the central nervous system (CNS) responses to
      dehydration (c-Fos and vasopressin mRNA) in mice lacking the ANG AT(1a) receptor
      [ANG AT(1a) knockout (KO)]. Control and AT(1a) KO mice were dehydrated for 24 or
      48 h. Baseline plasma vasopressin (VP) was not different between the groups;
      however, the response to dehydration was attenuated in AT(1a) KO (24 +/- 11 vs.
      10.6 +/- 2.7 pg/ml). Dehydration produced similar increases in plasma osmolality
      and depletion of posterior pituitary VP content. Neuronal activation was observed
      as increases in c-Fos protein and VP mRNA. The supraoptic responses were not
      different between groups. In the paraventricular nucleus (PVN), c-Fos-positive
      neurons (57.4 +/- 10.7 vs. 98.4 +/- 7.4 c-Fos cells/PVN, control vs. AT(1a) KO)
      and VP mRNA levels (1.0 +/- 0.1 vs. 1.4 +/- 0.1 microCi, control vs. AT(1a) KO)
      were increased with greater responses in AT(1a) KO. A comparison of 1- to 2-day
      water deprivation showed that plasma VP, brain c-Fos, and VP mRNA returned toward
      control on day 2, although plasma osmolality remained high. Data demonstrate that
      AT(1a) KO mice show a dichotomous response to dehydration, reduced for plasma VP
      and enhanced for PVN c-Fos protein and VP mRNA. The results illustrate the
      importance of ANG AT(1a) receptors in the regulation of osmotic and endocrine
      balance.

PMID- 11247839
TI  - Adaptation of intestinal production of apolipoprotein A-IV during chronic feeding
      of lipid.
AB  - We examined the effect of daily fat supplementation on intestinal gene expression
      and protein synthesis and plasma levels of apolipoprotein A-IV (apo A-IV). Rats
      were fasted overnight and then given intragastric bolus infusion of either saline
      or fat emulsion after 0, 1, 2, 4, 8, or 16 days of similar daily feedings. Four
      hours after the final saline or fat infusion, plasma and jejunal mucosa were
      harvested; plasma levels of apo A-IV, triglycerides, and leptin were measured, as
      well as mucosal apo A-IV mRNA levels and biosynthesis of apo A-IV protein. In
      response to fat, plasma apo A-IV showed an initial 40% increase compared with
      saline-injected control rats; with continued daily fat feeding, the plasma A-IV
      response showed rapid and progressive diminution such that by 4 days, plasma A-IV
      was not different between fat- and saline-fed groups. Jejunal mucosal apo A-IV
      synthesis and mRNA levels also showed time-dependent refractoriness to fat
      feeding. However, the kinetics of this effect were considerably slower than in
      the case of plasma, requiring 16 days for completion. There was no correlation
      between plasma leptin or triglyceride levels and intestinal apo A-IV synthesis or
      plasma apo A-IV. These results indicate rapid, fat-induced, posttranslational
      adapation of plasma apo A-IV levels and a slower, but similarly complete
      pretranslational adaptation of intestinal apo A-IV production, which are
      independent of plasma levels of leptin.

PMID- 11247840
TI  - Brain angiotensin receptors and sympathoadrenal regulation during insulin-induced
      hypoglycemia.
AB  - Simultaneous blockade of systemic AT1 and AT2 receptors or converting enzyme
      inhibition (CEI) attenuates the hypoglycemia-induced reflex increase of
      epinephrine (Epi). To examine the role of brain AT1 and AT2 receptors in the
      reflex regulation of Epi release, we measured catecholamines, hemodynamics, and
      renin during insulin-induced hypoglycemia in conscious rats pretreated
      intracerebroventricularly with losartan, PD-123319, losartan and PD-123319, or
      vehicle. Epi and norepinephrine (NE) increased 60-and 3-fold, respectively.
      However, the gain of the reflex increase in plasma Epi (Deltaplasma
      Epi/Deltaplasma glucose) and the overall Epi and NE responses were similar in all
      groups. The ensuing blood pressure response was similar between groups, but the
      corresponding bradycardia was augmented after PD-123319 (P < 0.05 vs. vehicle) or
      combined losartan and PD-123319 (P < 0.01 vs. vehicle). The findings indicate 1)
      brain angiotensin receptors are not essential for the reflex regulation of Epi
      release during hypoglycemia and 2) the gain of baroreceptor-mediated bradycardia
      is increased by blockade of brain AT2 receptors in this model.

PMID- 11247844
TI  - Ambient temperature modulates hypoxic-induced changes in rat body temperature and
      activity differentially.
AB  - When rats, acclimated to an ambient temperature (T(a)) of 29 degrees C, are
      exposed to 10% O(2) for 63 h, the circadian rhythms of body temperature (T(b))
      and level of activity (L(a)) are abolished, T(b) falls to a hypothermic nadir
      followed by a climb to a hyperthermic peak, L(a) remains depressed (Bishop B,
      Silva G, Krasney J, Salloum A, Roberts A, Nakano H, Shucard D, Rifkin D, and
      Farkas G. Am J Physiol Regulatory Integrative Comp Physiol 279: R1378-R1389,
      2000), and overt brain pathology is detected (Krasney JA, Farkas G, Shucard DW,
      Salloum AC, Silva G, Roberts A, Rifkin D, Bishop B, and Rubio A. Soc Neurosci
      Abstr 25: 581, 1999). To determine the role of T(a) in these hypoxic-induced
      responses, T(b) and L(a) data were detected by telemetry every 15 min for 48 h on
      air, followed by 63 h on 10% O(2) from rats acclimated to 25 or 21 degrees C.
      Magnitudes and rates of decline in T(b) after onset of hypoxia were inversely
      proportional to T(a), whereas magnitudes and rates of T(b) climb after the
      hypothermic nadir were directly proportional to T(a). No hyperthermia, so
      prominent at 29 degrees C, occurred at 25 or 21 degrees C. The hypoxic depression
      of L(a) was least at 21 degrees C and persisted throughout the hypoxia. In
      contrast, T(a) was a strong determinant of the magnitudes and time courses of the
      initial fall and subsequent rise in T(b). We propose that the absence of
      hyperthermia at 21 and 25 degrees C as well as a persisting hypothermia may
      protect the brain from overt pathology.

PMID- 11247845
TI  - Control of vascular tone in notothenioid fishes is determined by phylogeny, not
      environmental temperature.
AB  - We examined potential vasomotor control mechanisms in an Antarctic fish
      (Trematomus bernacchii; usual core temperature approximately -1 degrees C),
      comparing sensitivity to agonists by means of the cumulative dose response and
      potency with reference to depolarization by 50 mM KCl. In efferent branchial
      arteries, norepinephrine (NE) produced approximately 20% of the maximal KCl
      tension and ~40% in the presence of 10(-3)M sotalol, suggesting a modest
      contribution of alpha- and beta-adrenergic tonus [half-maximal response (pEC(50))
      = 6.29 +/- 0.37 M]. Carbachol (CBC) and serotonin (5-HT) had different
      sensitivities (pEC(50) = 4.50 +/- 0.40 and 6.82 +/- 0.08 M, respectively) but
      similar potencies (21.6 +/- 11.1 and 31.1 +/- 5.3% of KCl). A related species
      from warmer waters around New Zealand, Paranotothenia angustata, had similar
      vascular reactivity for NE (pEC(50) = 5.48 +/- 0.31 M), CBC (pEC(50) = 4.94 +/-
      0.22 M), and methysergide-sensitive vasoconstriction with 5-HT (pEC(50) = 6.22 +/
      0.40 M). Agonist potencies were 9, 65, and 45% that of KCl, respectively.
      Bovichtus variegatus, a member of the phylogenetic sister group to the
      notothenioids, also gave broadly similar responses. In contrast, Dissostichus
      mawsoni, a pelagic Antarctic notothenioid, showed a dominance of vasodilatation
      over vasoconstriction, with sensitive isoprenaline (pEC(50) = 6.66 +/- 0.05 M)
      but weak serotonergic (5.2 +/- 1.5% KCl) responses. The unusual dominance of
      serotonergic control appears to be primarily a consequence of evolutionary
      lineage rather than low environmental temperature, but the pattern may be
      modified according to functional demand.

PMID- 11247843
TI  - Identification of the suprachiasmatic nucleus in birds.
AB  - Circadian rhythms are generated by an internal biological clock. The
      suprachiasmatic nucleus (SCN) in the hypothalamus is known to be the dominant
      biological clock regulating circadian rhythms in mammals. In birds, two nuclei,
      the so-called medial SCN (mSCN) and the visual SCN (vSCN), have both been
      proposed to be the avian SCN. However, it remains an unsettled question which
      nuclei are homologous to the mammalian SCN. We have identified circadian clock
      genes in Japanese quail and demonstrated that these genes are expressed in known
      circadian oscillators, the pineal and the retina. Here, we report that these
      clock genes are expressed in the mSCN but not in the vSCN in Japanese quail, Java
      sparrow, chicken, and pigeon. In addition, mSCN lesions eliminated or
      disorganized circadian rhythms of locomotor activity under constant dim light,
      but did not eliminate entrainment under light-dark (LD) cycles in pigeon.
      However, the lesioned birds became completely arrhythmic even under LD after the
      pineal and the eye were removed. These results indicate that the mSCN is a
      circadian oscillator in birds.

PMID- 11247846
TI  - A molecular explanation for the long-term suppression of circadian rhythms by a
      single light pulse.
AB  - With the use of a molecular model for circadian rhythms in Drosophila based on
      transcriptional regulation, we show how a single, critical pulse of light can
      permanently suppress circadian rhythmicity, whereas a second light pulse can
      restore the abolished rhythm. The phenomena occur via the pulsatile induction of
      either protein degradation or gene expression in conditions in which a stable
      steady state coexists with stable circadian oscillations of the limit cycle type.
      The model indicates that suppression by a light pulse can only be accounted for
      by assuming that the biochemical effects of such a pulse much outlast its actual
      duration. We determine the characteristics of critical pulses suppressing the
      oscillations as a function of the phase at which the rhythm is perturbed. The
      model predicts how the amplitude and duration of the biochemical changes induced
      by critical pulses vary with this phase. The results provide a molecular, dynamic
      explanation for the long-term suppression of circadian rhythms observed in a
      variety of organisms in response to a single light pulse and for the subsequent
      restoration of the rhythms by a second light pulse.

PMID- 11247847
TI  - Vagotomy attenuates tumor necrosis factor-alpha-induced sleep and EEG delta
      activity in rats.
AB  - Much evidence suggests that tumor necrosis factor-alpha (TNF-alpha) is involved
      in the regulation of physiological sleep. However, it remains unclear whether
      peripheral administration of TNF-alpha induces sleep in rats. Furthermore, the
      role of the vagus nerve in the somnogenic actions of TNF-alpha had not heretofore
      been studied. Four doses of TNF-alpha were administered intraperitoneally just
      before the onset of the dark period. The three higher doses of TNF-alpha (50,
      100, and 200 microg/kg) dose dependently increased nonrapid eye movement sleep
      (NREMS), accompanied by increases in electroencephalogram (EEG) slow-wave
      activity. TNF-alpha increased EEG delta-power and decreased EEG alpha- and beta
      power during the initial 3 h after injection. In vagotomized rats, the NREMS
      responses to 50 or 100 microg/kg of TNF-alpha were attenuated, while significant
      TNF-alpha-induced increases in NREMS were observed in a sham-operated group.
      Moreover, the vagotomized rats failed to exhibit the increase in EEG delta-power
      induced by TNF-alpha intraperitoneally. These results suggest that peripheral TNF
      alpha can induce NREMS and vagal afferents play an important role in the effects
      of peripheral TNF-alpha and EEG synchronization on sleep. Intraperitoneal TNF
      alpha failed to affect brain temperature at the doses tested, thereby
      demonstrating that TNF-alpha-induced sleep effects are, in part, independent from
      its effects on brain temperature. Results are consistent with the hypothesis that
      a cytokine network is involved in sleep regulation.

PMID- 11247848
TI  - Metabolic consequences of a species difference in Gibbs free energy of Na+/Ca2+
      exchange: rat versus guinea pig.
AB  - The Gibbs free energy of the sarcolemmal Na+/Ca2+ exchanger (DeltaG(Na/Ca))
      determines its net Ca2+ flux. We tested the hypothesis that a difference of
      diastolic DeltaG(Na/Ca) exists between rat and guinea pig myocardium. We measured
      the suprabasal rate of oxygen consumption (VO2) of arrested Langendorff-perfused
      hearts of both species, manipulating DeltaG(Na/Ca) by reduction of extracellular
      Na+ concentration, [Na+](o). Hill equations fitted to the resulting VO2-[Na+](o)
      relationships yielded Michaelis constant (K(m)) values of 67 and 25 mM for rat
      and guinea pig, respectively. We developed and tested a simple thermodynamic
      model that attributes this difference of K(m) values to a 7.84 kJ/mol difference
      of DeltaG(Na/Ca). The model predicts that reversal of Na+/Ca2+ exchange, leading
      to diastolic Ca2+ influx, should occur at a value of [Na+](o) about three times
      higher in rat myocardium. We verified this quantitative prediction using fura 2
      fluorescence to index intracellular Ca2+ concentration in isolated ventricular
      trabeculae at 37 degrees C. The postulated difference in free energy of Na+/Ca2+
      exchange explains a number of reported disparities of Ca2+ handling at rest
      between rat and guinea pig myocardia.

PMID- 11247849
TI  - IGFs stimulate zebrafish cell proliferation by activating MAP kinase and PI3
      kinase-signaling pathways.
AB  - Insulin-like growth factor (IGF)-I and -II have been cloned from a number of
      teleost species, but their cellular actions in fish are poorly defined. In this
      study, we show that both IGF-I and -II stimulated zebrafish embryonic cell
      proliferation and DNA synthesis in a concentration-dependent manner, whereas
      insulin had little mitogenic activity. Affinity cross-linking and immunoblotting
      studies revealed the presence of IGF receptors with the characteristics of the
      mammalian type I IGF receptor. Competitive binding assay results indicated that
      the binding affinities of the zebrafish IGF-I receptors to IGF-I, IGF-II, and
      insulin are 1.9, 2.6, and >190 nM, indicating that IGF-I and -II bind to the IGF
      I receptor(s) with approximately equal high affinity. To further investigate the
      cellular mechanism of IGF actions, we have studied the effects of IGFs on two
      major signal transduction pathways: mitogen-activated protein kinase (MAPK) and
      phosphatidylinositol 3-kinase (PI3 kinase). IGFs activated MAPK in zebrafish
      embryonic cells in a dose-dependent manner. This activation occurred within 5 min
      of IGF-I stimulation and disappeared after 1 h. IGF-I also caused a concentration
      dependent activation of protein kinase B, a downstream target of PI3 kinase, this
      activation being sustained for several hours. Inhibition of MAPK activation by
      the MAPK kinase inhibitor PD-98059 inhibited the IGF-I-stimulated DNA synthesis.
      Similarly, use of the PI3 kinase inhibitor LY-294002 also inhibited IGF-I
      stimulated DNA synthesis. When both the MAPK and PI3 kinase pathways were
      inhibited using a combination of these compounds, the IGF-I-stimulated DNA
      synthesis was completely negated. These results indicate that both IGF-I and -II
      are potent mitogens for zebrafish embryonic cells and that activation of both the
      MAPK and PI3 kinase-signaling pathways is required for the mitogenic action of
      IGFs in zebrafish embryonic cells.

PMID- 11247850
TI  - Impaired muscle oxygen transfer in patients with chronic renal failure.
AB  - We hypothesized that impaired O2 transport plays a role in limiting exercise in
      patients with chronic renal failure (CRF). Six CRF patients (25 +/- 6 yr) and six
      controls (24 +/- 6 yr) were examined twice during incremental single-leg isolated
      quadriceps exercise. Leg O2 delivery (QO2(leg)) and leg O2 uptake (VO2(leg)) were
      obtained when subjects breathed gas of three inspired O2 fractions (FI(O2))
      (0.13, 0.21, and 1.0). On a different day, myoglobin O2 saturation and muscle
      bioenergetics were measured by proton and phosphorus magnetic resonance
      spectroscopy. CRF patients, but not controls, showed O2 supply dependency of peak
      VO2 (VO2(peak)) by a proportional relationship between peak VO2(leg) at each
      inspired O2 fraction (0.59 +/- 0.20, 0.47 +/- 0.10, 0.43 +/- 0.10 l/min,
      respectively) and 1) work rate (933 +/- 372, 733 +/- 163, 667 +/- 207 g), 2)
      QO(2leg) (0.80 +/- 0.20, 0.64 +/- 0.10, 0.59 +/- 0.10 l/min), and 3) cell PO2
      (6.3 +/- 5.4, 1.7 +/- 1.3, 1.2 +/- 0.7 mmHg). CRF patients breathing 100% O2 and
      controls breathing 21% O2 had similar peak QO2(leg) (0.80 +/- 0.20 vs. 0.79 +/-
      0.10 l/min) and similar peak VO2(leg) (0.59 +/- 0.20 vs. 0.57 +/- 0.10 l/min).
      However, mean capillary PO2 (47.9 +/- 4.0 vs. 38.2 +/- 4.6 mmHg) and the
      capillary-to-myocite gradient (40.7 +/- 6.2 vs. 34.4 +/- 4.0 mmHg) were both
      higher in CRF patients than in controls (P < 0.03 each). We conclude that low
      muscle O2 conductance, but not limited mitochondrial oxidative capacity, plays a
      role in limiting exercise tolerance in these patients.

PMID- 11247851
TI  - Effects of age and photoperiod on reproduction and the spleen in the marsh rice
      rat (Oryzomys palustris).
AB  - To examine the interactions between age and photoperiod on reproduction and
      spleen weights, we exposed adult male and female rice rats of various ages to
      photoperiods of 16:8-h light-dark photoperiods (16L:8D) or 12L:12D. After 10 wk,
      animals were killed and the following data were recorded: weights of testes,
      seminal vesicles, uterus, ovaries, body, and spleen and, in addition, vaginal
      patency. Young adult males displayed a greater degree of testicular and seminal
      vesicle regression in short photoperiods than did older males; the testes of most
      older males did not regress in response to short photoperiods. Spleen weight was
      unresponsive to short photoperiods in all males, but was affected by age.
      Females, however, exhibited reproductive organ regression and decreased vaginal
      patency in response to short photoperiods at all ages examined. Body weights were
      affected by photoperiod in young females, and, as in males, photoperiod had no
      effect on spleen weights. These data suggest that the reproductive response to
      photoperiod in adult male rice rats declines with age, whereas in adult females
      it does not.

PMID- 11247852
TI  - Skeletal muscle calcineurin: influence of phenotype adaptation and atrophy.
AB  - Calcineurin (CaN) has been implicated as a signaling molecule that can transduce
      physiological stimuli (e.g., contractile activity) into molecular signals that
      initiate slow-fiber phenotypic gene expression and muscle growth. To determine
      the influence of muscle phenotype and atrophy on CaN levels in muscle, the levels
      of soluble CaN in rat muscles of varying phenotype, as assessed by myosin heavy
      chain (MHC)-isoform proportions, were determined by Western blotting. CaN levels
      were significantly greater in the plantaris muscle containing predominantly fast
      (IIx and IIb) MHC isoforms, compared with the soleus (predominantly type I MHC)
      or vastus intermedius (VI, contains all 4 adult MHC isoforms). Three months after
      a complete spinal cord transection (ST), the CaN levels in the VI muscle were
      significantly reduced, despite a significant increase in fast MHC isoforms.
      Surprisingly, the levels of CaN in the VI were highly correlated with muscle mass
      but not MHC isoform proportions in ST and control rats. These data demonstrate
      that CaN levels in skeletal muscle are highly correlated to muscle mass and that
      the normal relationship with phenotype is lost after ST.

PMID- 11247854
TI  - An unexpected cause of muscle pain in diabetes.
AB  - Diabetic muscle infarction is a rare condition which may present to a
      rheumatologist. It was first reported in 1965. Two illustrative cases are
      described here and the mechanisms of pathogenesis discussed. Analysis of the
      published data, results of the muscle biopsies, and a technetium-99m sestamibi
      scan suggest that the condition, which occurs against a background of diabetic
      microangiopathy, can be triggered by an ischaemic event and causes extensive
      muscle necrosis through hypoxia-reperfusion injury and compartment syndrome.

PMID- 11247855
TI  - Unusual and memorable.

PMID- 11247853
TI  - Stem cells for repair of cartilage and bone: the next challenge in osteoarthritis
      and rheumatoid arthritis.

PMID- 11247858
TI  - Immunohistological study of entheses in spondyloarthropathies: comparison in
      rheumatoid arthritis and osteoarthritis.
AB  - OBJECTIVE: To determine which inflammatory cell types are present in entheses
      from patients with spondyloarthropathy (SpA) compared with patients with
      rheumatoid arthritis (RA) or osteoarthritis (OA). METHODS: Enthesis specimens
      were obtained during orthopaedic procedures in eight patients with SpA, four with
      RA, and three with OA. After decalcification, the lymphocyte subsets (CD3, CD4,
      CD8, CD20) in the bone marrow component of each enthesis were measured by an
      immunohistochemical technique. RESULTS: Oedema and an inflammatory infiltrate
      were present in all the SpA specimens, being clearly predominant in the bone
      marrow component of the entheses. The density of all cell types in the bone
      marrow was significantly higher in the SpA group than in the two other groups.
      The cell type CD3+ showed the greatest difference between the SpA and RA groups,
      being increased fivefold in the SpA group. Within the SpA group, CD3+ cells were
      considerably more numerous than CD20+ cells-a difference from the RA group-and
      the predominant T cells were CD8+. CONCLUSION: Persistent oedema with an
      inflammatory infiltrate composed predominantly of CD8+ cells was noted in the
      entheses of patients with SpA, being predominant in the bone marrow. These
      results suggest that CD8+ cells may have a key role in local inflammation in
      SpAs.

PMID- 11247859
TI  - Bone destruction, upward migration, and medialisation of rheumatoid shoulder: a
      15 year follow up study.
AB  - OBJECTIVE: To evaluate bone destruction, upward migration, and medialisation of
      the glenohumeral (GH) joint in a cohort of 74 patients with seropositive and
      erosive rheumatoid arthritis followed up prospectively. METHODS: At the 15 year
      follow up 148 shoulders were radiographed by a standard method. Bone destruction
      in the GH joint was examined from the radiographs by four methods, of which three
      measured the migration and one the remodelling of the humeral head. The distances
      from the greater tuberosity of the humeral head to the coracoid process
      (medialisation distance (MD)) and to the articular surface of the humeral head
      (GA) have been previously developed to evaluate the preoperative offsets of the
      arthritic GH joint. Medial displacement index (MI) and upward migration index
      (UI) have been recently developed to evaluate the destructive pattern of the
      rheumatoid GH joint. Destruction of the GH joints was assessed by the Larsen
      method on a scale of 0 to 5. The relation between the measurements and the grade
      of destruction of the GH joints was examined. UI was compared with our previous
      measurements of the subacromial space. RESULTS: Both the MI and the UI had a
      negative correlation with the GH joint destruction (Larsen grade), r=-0.49 (95%
      CI -0.36 to -0.60) and r=-0.58 (95% CI -0.46 to -0.68). The UI correlated
      significantly with the subacromial space, r=0.90 (95% CI 0.86 to 0.93). The mean
      MI and UI measurements of the non-affected joints were within the reported normal
      variation. The mean MD collapsed between Larsen grades 4 (83.0 mm) and 5 (65.5
      mm). The morphology of the humeral head began to flatten and erode from the grade
      3 onwards and medial head destruction was detected at grade 5. CONCLUSIONS:
      Medialisation seems to be preceded by upward migration of the humeral head,
      indicating rotator cuff damage. Symptomatic Larsen grade 3 shoulders should be
      intensively followed up by clinical and radiological means. If a total shoulder
      arthroplasty is considered, an orthopaedic consultation is worthwhile at a
      sufficiently early stage (Larsen 3 and 4), when soft tissue structures
      responsible for function are still in proper condition and timing of the
      operative procedure can be well planned.

PMID- 11247860
TI  - A prospective study of renal disease in patients with early rheumatoid arthritis.
AB  - OBJECTIVES: This prospective study was designed to clarify the frequency, causes,
      and clinical course of renal disease in patients with early rheumatoid arthritis
      (RA). METHODS: 235 patients (185 women, mean age 49.4 years) with early RA of
      less than one year's duration were enrolled and assessed monthly. Proteinuria was
      defined as a positive dipstick result and microscopic haematuria was defined as
      the presence of > or =5 red blood cells per high power field. Urinary
      abnormalities lasting three months or longer were defined as persistent
      abnormalities. RESULTS: At entry, 40 patients exhibited haematuria, two had a
      raised serum creatinine concentration, and none had proteinuria. During the
      observation period (average 42 months), persistent haematuria was found in 43,
      persistent proteinuria in 17, and a raised serum creatinine concentration in 14
      patients. Persistent proteinuria was caused by drugs in 14 of 17 patients and
      disappeared in most cases. Risk factors for drug induced proteinuria included a
      raised C reactive protein and erythrocyte sedimentation rate and age over 50 at
      entry. Drugs resulted in a raised serum creatinine concentration in eight of 14
      patients. The incidence of haematuria at entry did not differ among patients who
      had been treated with non-steroidal anti-inflammatory drugs, disease modifying
      antirheumatic drugs, or no drugs. In some patients with isolated haematuria, the
      haematuria appeared when the activity of RA was high and resolved when it was
      low. CONCLUSIONS: This study suggests that a raised serum creatinine
      concentration or persistent proteinuria in patients with early RA is
      predominantly drug related whereas, in contrast, isolated haematuria is more
      directly associated with the activity of the disease process.

PMID- 11247861
TI  - Users of oestrogen replacement therapy have more knee cartilage than non-users.
AB  - BACKGROUND: Osteoarthritis (OA) is increasingly prevalent in the years after
      menopause. Epidemiological data suggest that the use of oestrogen replacement
      therapy (ERT) may protect against knee OA. AIM: To test the hypothesis that long
      term ERT (longer than five years) is associated with increased knee cartilage in
      postmenopausal women. METHODS: The study involved 81 women (42 current users (>
      or = five years) of ERT and 39 who had never used it). Articular cartilage
      volumes were determined by processing images acquired in the sagittal plane using
      a T1 weighted fat suppressed magnetic resonance sequence on an independent work
      station. RESULTS: After bone size had been accounted for, ERT users had higher
      tibial cartilage volume than non-users. Total tibial cartilage volume was 7.7%
      (0.23 ml) greater in the group of ERT users (2.98 (0.47) ml; mean (SD)) than in
      the untreated group (2.75 (0.50) ml). The difference, after adjustment for the
      significant explanatory factors (years since menopause, body mass index, age at
      menopause, and smoking), between the ERT users and non-users increased from 0.23
      ml to 0.30 ml (95% confidence interval 0.08 to 0.52, p=0.008). These differences
      persisted after exclusion of women with OA. CONCLUSIONS: After adjustment for
      multiple confounders, women using long term ERT have more knee cartilage than
      controls. This may indicate that ERT prevents loss of knee articular cartilage.

PMID- 11247863
TI  - Does the Stanford Health Assessment Questionnaire have potential as a monitoring
      tool for subjects with rheumatoid arthritis?
AB  - OBJECTIVE: To assist in the interpretation of the Stanford Health Assessment
      Questionnaire (HAQ) score changes for individual patients with rheumatoid
      arthritis (RA), by determining the minimum size of score change that can
      confidently be considered to reflect a significant change in disability from the
      patient's perspective. METHOD: HAQ score changes were calculated for 40 clinic
      patients with RA who had reported no change to health in general over two months.
      These were considered to reflect both inconsistencies in questionnaire completion
      and any true but minor changes not considered significant enough by the patients
      to represent a change to their health in general. HAQ score changes over one year
      were also calculated for 207 clinic patients with RA. RESULTS: The range within
      which 95% of score changes would be expected to lie in the absence of significant
      change was estimated as +/-0.48 points (+/-2SD of the score changes) and 80%
      within +/-0.31 points (+/-1.29SD). A chi(2) test showed no significant
      association between an HAQ score increase of >0.31 over one year and decline in
      health related to arthritis reported by the patient over the same period.
      CONCLUSION: As a general guideline, an HAQ score needs to change by 0.48 points
      or more for 95% confidence that it reflects significant change (0.31 for 80%
      confidence). Although the value of HAQ as a group outcome measure is well
      established, this study questions the usefulness of monitoring individual HAQ
      scores in a clinical setting.

PMID- 11247864
TI  - Reporting of outcomes in arthritis trials measured on ordinal and interval scales
      is inadequate in relation to meta-analysis.
AB  - OBJECTIVES: To study whether the reporting of clinical outcomes in arthritis
      trials measured on ordinal and interval scales is adequate in relation to meta
      analysis. METHODS: Systematic review of randomised trials of non-steroidal anti
      inflammatory drugs in patients with rheumatoid arthritis. Optimal reporting was
      defined as data in the original ordered categories for global evaluation and
      pain, and as mean and SD for number of tender joints and grip strength, and if a
      visual analogue scale had been used to measure pain. RESULTS: A total of 144
      trials were included. The median sample size was 60 patients. The quality of the
      reporting increased over time for three of the four variables. Global evaluation
      was optimally reported in 52 of the 127 trials (41%) in which it was recorded.
      Pain was optimally reported in 27 of 98 trials (28%), number of tender joints in
      41 of 123 trials (33%), and grip strength in 34 of 124 trials (27%). Even if
      rather broad criteria are adopted, only about half of the data were reported in a
      potentially useful way for a meta-analysis. CONCLUSIONS: Arthritis trials have
      been reported inadequately in relation to meta-analysis. As most trials are
      underpowered, meta-analysis is indispensable and the deficit therefore needs
      urgent improvement. Investigators should specify a priori what constitutes an
      important treatment effect and report numbers of patients improved.

PMID- 11247862
TI  - Frequency of triggering bacteria in patients with reactive arthritis and
      undifferentiated oligoarthritis and the relative importance of the tests used for
      diagnosis.
AB  - OBJECTIVE: Reactive arthritis (ReA) triggered by Chlamydia trachomatis or enteric
      bacteria such as yersinia, salmonella, Campylobacter jejuni, or shigella is an
      important differential diagnosis in patients presenting with the clinical picture
      of an undifferentiated oligoarthritis (UOA). This study was undertaken to
      evaluate the best diagnostic approach. PATIENTS AND METHODS: 52 patients with
      ReA, defined by arthritis and a symptomatic preceding infection of the gut or the
      urogenital tract, and 74 patients with possible ReA, defined by oligoarthritis
      without a preceding symptomatic infection and after exclusion of other diagnoses
      (UOA), were studied. The following diagnostic tests were applied for the
      identification of the triggering bacterium: for yersinia induced ReA-stool
      culture, enzyme immunoassay (EIA), and Widal's agglutination test for detection
      of antibodies to yersinia; for salmonella or campylobacter induced ReA-stool
      culture, EIA for the detection of antibodies to salmonella and Campylobacter
      jejuni; for infections with shigella-stool culture; for infections with Chlamydia
      trachomatis-culture of the urogenital tract, microimmunofluorescence and
      immunoperoxidase assay for the detection of antibodies to Chlamydia trachomatis.
      RESULTS: A causative pathogen was identified in 29/52 (56%) of all patients with
      ReA. In 17 (52%) of the patients with enteric ReA one of the enteric bacteria was
      identified: salmonella in 11/33 (33%) and yersinia in 6/33 (18%). Chlamydia
      trachomatis was the causative pathogen in 12/19 (63%) of the patients with
      urogenic ReA. In patients with the clinical picture of UOA a specific triggering
      bacterium was also identified in 35/74 (47%) patients: yersinia in 14/74 (19%),
      salmonella in 9/74 (12%), and Chlamydia trachomatis in 12/74 (16%). CONCLUSIONS:
      Chlamydia trachomatis, yersinia, and salmonella can be identified as the
      causative pathogen in about 50% of patients with probable or possible ReA if the
      appropriate tests are used.

PMID- 11247865
TI  - Employment, work disability, and work days lost in patients with ankylosing
      spondylitis: a cross sectional study of Dutch patients.
AB  - OBJECTIVE: To evaluate employment status, work disability, and work days lost in
      patients with ankylosing spondylitis (AS). METHODS: A questionnaire was sent to
      709 patients with AS aged 16-60. The results of 658 of the patients could be
      analysed. RESULTS: After adjustment for age, labour force participation was
      decreased by 15.4% in male patients and 5.2% in female patients compared with the
      general Dutch population. Work disability (all causes) was 15.7% and 16.9% higher
      than expected in the general population for male and female patients
      respectively. In particular, the proportion of those with a partial work
      disability pension was increased. Patients with a paid job lost 5.0% of work days
      as the result of having AS, accounting for a mean of 10.1 days of sick leave due
      to AS per patient per year in addition to the national average of 12.3
      unspecified days of sick leave. CONCLUSION: This study on work status in AS
      provides data adjusted for age and sex, and the differences from the reference
      population were significant. The impact of AS on employment and work disability
      is considerable. Work status in patients with AS needs more attention as an
      outcome measure in future research.

PMID- 11247866
TI  - Antibiotic prophylaxis for haematogenous bacterial arthritis in patients with
      joint disease: a cost effectiveness analysis.
AB  - OBJECTIVE: To assess the cost effectiveness of antibiotic prophylaxis for
      haematogenous bacterial arthritis in patients with joint disease. METHODS: In a
      decision analysis, data from a prospective study on bacterial arthritis in 4907
      patients with joint disease were combined with literature data to assess risks
      and benefits of antibiotic prophylaxis. Effectiveness and cost effectiveness
      calculations were performed on antibiotic prophylaxis for various patient groups.
      Grouping was based on (a) type of event leading to transient bacteraemia-that is,
      infections (dermal, respiratory/urinary tract) and invasive medical procedures
      and (b) the patient's susceptibility to bacterial arthritis which was increased
      in the presence of rheumatoid arthritis, large joint prostheses, comorbidity, and
      old age. RESULTS: Of the patients with joint disease, 59% had no characteristics
      that increased susceptibility to bacterial arthritis, and 31% had one. For dermal
      infections, the effectiveness of antibiotic prophylaxis was maximally 35 quality
      adjusted life days (QALDs) and the cost effectiveness maximally $52 000 per
      quality adjusted life year (QALY). For other infections, the effectiveness of
      prophylaxis was lower and the cost effectiveness higher. Prophylaxis for invasive
      medical procedures seemed to be acceptable only in patients with high
      susceptibility: 1 QALD at a cost of $1300/QALY; however, the results were
      influenced substantially when the level of efficacy of the prophylaxis or cost of
      prophylactic antibiotics was changed. CONCLUSION: Prophylaxis seems to be
      indicated only for dermal infections, and for infections of the urinary and
      respiratory tract in patients with increased susceptibility to bacterial
      arthritis. Prophylaxis for invasive medical procedures, such as dental treatment,
      may only be indicated for patients with joint disease who are highly susceptible.

PMID- 11247867
TI  - Epidemiology of biopsy proven giant cell arteritis in northwestern Spain: trend
      over an 18 year period.
AB  - OBJECTIVE: In Europe giant cell arteritis (GCA) is more common in Scandinavian
      countries than in southern regions. Epidemiological studies on GCA in other more
      distant countries have indicated a progressive increase in incidence. A regular
      cyclical pattern in incidence of GCA over 20 years has been reported in Olmsted
      County (Minnesota, USA). In contrast, no cyclical fluctuation has been recently
      reported in Sweden. To investigate further the epidemiology of GCA in southern
      Europe the trend in incidence and fluctuations of this vasculitis over 18 years
      in the Lugo region of northwestern Spain were examined. METHODS: A retrospective
      study of biopsy proven GCA diagnosed between 1 January 1981 and 31 December 1998
      at a single hospital for a well defined population of almost 250 000 people.
      Annual incidence was calculated for the whole group of patients and for men and
      women separately. Monthly variations, annual peaks of incidence, and trend in the
      incidence of biopsy proven GCA with and without polymyalgia rheumatica (PMR) were
      also examined. RESULTS: One hundred and sixty one Lugo residents were diagnosed
      with biopsy proven GCA between 1981 and 1998. The average annual incidence for
      the population aged 50 and older was 10.24/100 000 (men 11.00/100 000, women
      9.57/100 000). A progressive increase in the incidence in both men and women was
      seen. In men there was an annual increase of 8% (95% CI 4% to 13%; p<0.0001). In
      women the annual increase was 11% (95% CI 5% to 17%; p<0.0001). The overall
      annual increase for men and women was 10% (95% CI 6% to 14%; p<0.0001). No
      seasonal pattern or peaks in the incidence were seen. During the period 1981-94
      GCA was more common in men than in women. In contrast, during the last years of
      study the increase in incidence was higher in women. In women the annual ratio of
      incidence of GCA with PMR/incidence of GCA without PMR was generally higher than
      1. However, in men the annual ratio was initially 1 but decreased gradually,
      indicating a progressive decrease in the proportion of men with biopsy proven GCA
      associated with PMR. CONCLUSION: In northwestern Spain there has been a
      progressive increase in GCA incidence. As seen in other countries where GCA is
      more common, during the past few years the increase in incidence has been mainly
      due to a higher number of new cases in women.

PMID- 11247868
TI  - Increased levels of proinflammatory cytokines and nitric oxide metabolites in
      neuropsychiatric lupus erythematosus.
AB  - OBJECTIVE: To investigate systemic and intrathecal production of proinflammatory
      cytokines in relation to cerebrospinal fluid (CSF) nitric oxide (NO) release in
      patients with neuropsychiatric lupus erythematosus (NPLE). METHODS: Thirty
      patients with NPLE rated as mild, moderate, or severe were studied and CSF was
      obtained from 21 of these. Cytokine mRNA expressing cells were detected by in
      situ hybridisation. Soluble cytokines were assessed by enzyme linked
      immunosorbent assay (ELISA). Nitrite and nitrate were determined by capillary
      electrophoresis. RESULTS: Patients with NPLE had high numbers of lymphocytes
      expressing mRNA for tumour necrosis factor alpha (TNFalpha), interferon gamma,
      and interleukin 10 in blood. The number of peripheral blood TNFalpha mRNA
      positive cells correlated strongly with the level of NO metabolites in the CSF
      (r(2)=0.69). Both the number of peripheral blood mononuclear cells expressing
      mRNA for TNFalpha as well as the CSF level of NO metabolites correlated with NPLE
      disease severity. CONCLUSION: These data suggest that increased peripheral
      production of proinflammatory cytokines such as TNFalpha may contribute both to
      an increased production of NO in the central nervous system and to generation of
      clinical NPLE. The data also support the possibility that measurements of NO
      metabolites in CSF may be of value in the diagnosis of neurological symptoms
      related to SLE.

PMID- 11247869
TI  - Glucocorticosteroid dependent decrease in the activity of calcineurin in the
      peripheral blood mononuclear cells of patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To compare the activity of calcineurin in the peripheral blood
      mononuclear cells (PBMC) of 32 patients with systemic lupus erythematosus (SLE)
      and 35 healthy controls. METHODS: The activity of calcineurin was assayed in the
      supernatants of sonicated mononuclear cells. RESULTS: There was no significant
      difference in the calcineurin activity of patients with SLE not taking
      glucocorticosteroids (GCS) compared with the healthy controls. On the other hand,
      the activity of calcineurin was reduced in patients with SLE taking GCS,
      correlating negatively with the dose of GCS. The stimulation of PBMC by phorbol
      ester and calcium ionophore decreased the calcineurin activity both in patients
      with SLE and in healthy controls. GCS could also reduce calcineurin activity in
      the mononuclear cells of healthy subjects in vitro. CONCLUSIONS: In patients with
      SLE the decrease in the calcineurin activity of PBMC depended on the dose of GCS
      used for treatment, and it was not a disease specific alteration. The higher the
      dose of GCS, the greater the inhibition of calcineurin activity. The reduction of
      calcineurin activity is a new element in the immunosuppressive effects of GCS
      during the treatment of patients with SLE.

PMID- 11247870
TI  - Immunological and clinical follow up of hepatitis C virus associated
      cryoglobulinaemic vasculitis.
AB  - OBJECTIVE: To study immunological markers and compare these markers with standard
      measures for the clinical and immunological follow up of vasculitis activity in
      hepatitis C virus (HCV) associated cryoglobulinaemic vasculitis (CV). METHODS:
      Serial serum samples from eight patients with newly diagnosed HCV associated CV
      were followed during interferon alpha treatment induced remission of the CV.
      Vasculitis activity and disease extent were evaluated with the Birmingham
      vasculitis activity score (BVAS) and disease extent index (DEI).
      Cryoglobulinaemia, complement levels (C3c, C4, and CH50), rheumatoid factor (RF),
      autoantibodies such as antinuclear antibodies, soluble interleukin 2 receptor
      (sIL2r), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble CD30
      (sCD30) were determined. RESULTS: All patients achieved either complete or
      partial remission of their CV during interferon alpha treatment. There was a
      significant reduction in vasculitis activity and disease extent (BVAS, DEI),
      cryoglobulinaemia, RF, sIL2r, sICAM-1, and sCD30. Complement C3c levels increased
      significantly during this period. Erythrocyte sedimentation rate and levels of
      complement C4 and CH50 did not change significantly. Both clinical measures (BVAS
      and DEI) correlated significantly only with C3c and sCD30. CONCLUSIONS: Although
      this study was of only a small group of patients, it shows that BVAS and DEI as
      clinical measures and C3c and sCD30 as immunological markers may be useful in the
      follow up of disease activity of HCV associated CV. The data indicate that
      activity of the humoral (cryoglobulinaemia, RF, autoantibodies) and cellular
      (sIL2r, sICAM-1, sCD30) immune response and endothelial damage (sICAM-1) are
      found in HCV associated CV.

PMID- 11247871
TI  - Down regulation of interleukin 1beta production in human osteoarthritic synovial
      tissue and cartilage cultures by aminoguanidine.
AB  - OBJECTIVE: To evaluate the effect of aminoguanidine (AG) on de novo interleukin
      1beta (IL1beta), nitric oxide (NO), and interleukin 1 receptor antagonist (IL1ra)
      production by osteoarthritic human synovial tissue and articular cartilage
      cultures. METHODS: Synovial tissue and cartilage, obtained during surgery from 29
      patients undergoing total knee or hip replacement for osteoarthritis, were cut
      into small pieces and cultured in the presence or absence of lipopolysaccharide
      (LPS) and test materials. IL1beta, IL1ra, and NO were determined in culture
      media. The inducible nitric oxide synthase inhibitor, AG, was added to cultures
      in various concentrations (0.3-3 mmol/l). RESULTS: In synovial tissue cultures AG
      (0.3, 1, and 3 mmol/l) decreased LPS (1 microg/ml) stimulated IL1beta and NO
      release in the media in a dose dependent manner (p<0.05 at 1 mmol/l and p<0.05 at
      0.3 mmol/l, respectively). In articular cartilage cultures AG (0.3, 1, and 3
      mmol/l) decreased LPS (1 microg/ml) stimulated IL1beta and NO release in the
      media in a dose dependent manner (p<0.05 at 1 mmol/l and p<0.01 at 0.3 mmol/l,
      respectively). Hydrocortisone (5 microg/ml) also significantly decreased LPS
      stimulated IL1beta release in media of synovial tissue and cartilage cultures and
      NO in media of synovial cultures. AG (0.3, 1, and 3 mmol/l) decreased LPS (1
      microg/ml) stimulated IL1ra levels in media of synovial tissue cultures in a dose
      dependent manner (p<0.05 at 1 mmol/l) but increased LPS (1 microg/ml) stimulated
      IL1ra release in media of cartilage cultures (p<0.01 at 3 mmol/l). The NO donor,
      nitroprusside (10, 30, 100, and 300 microg/ml) stimulated IL1beta release in
      media of synovial tissue cultures in a dose dependent manner (p<0.01 at 100
      microg/ml). AG and nitroprusside at the concentrations used had no toxic effect
      on human synovial cells. CONCLUSIONS: NO synthase inhibitors may modulate
      osteoarthritis and articular inflammatory processes not only by decreasing NO
      synthesis but also by their effects on ILbeta and IL1ra production.

PMID- 11247872
TI  - Tensile properties of rat anterior cruciate ligament in collagen induced
      arthritis.
AB  - OBJECTIVES: To investigate the effects of collagen induced arthritis (CIA) on the
      tensile properties of rat anterior cruciate ligament (ACL). METHODS: The tensile
      strength, bone mineral density (BMD), and histology of ACL units from rats with
      CIA were investigated. RESULTS: The tensile strength of the ACL unit was
      significantly lower in the rats with CIA at 10 weeks after immunisation (ultimate
      failure load, 74.9% of the control; stiffness, 62.0% of the control). The major
      mode of failure was femoral avulsion, and the BMD was significantly lower in the
      rats with CIA. A histological examination of the ligament insertion in rats with
      CIA showed resorption of the cortical bone beneath the ACL insertion and an
      enlarged mineralised fibrocartilage zone. CONCLUSIONS: These findings indicate
      that the decrease in tensile strength of ACL units correlated with histological
      changes in the ligament-bone attachment, such as bone resorption beneath the
      ligament insertion site and an enlargement of the mineralised fibrocartilage
      zone.

PMID- 11247873
TI  - Basic calcium phosphate crystals activate human osteoarthritic synovial
      fibroblasts and induce matrix metalloproteinase-13 (collagenase-3) in adult
      porcine articular chondrocytes.
AB  - OBJECTIVE: To determine the ability of basic calcium phosphate (BCP) crystals to
      induce (a) mitogenesis, matrix metalloproteinase (MMP)-1, and MMP-13 in human
      osteoarthritic synovial fibroblasts (HOAS) and (b) MMP-13 in cultured porcine
      articular chondrocytes. METHODS: Mitogenesis of HOAS was measured by
      [3H]thymidine incorporation assay and counts of cells in monolayer culture. MMP
      messenger RNA (mRNA) accumulation was determined either by northern blot analysis
      or reverse transcriptase-polymerase chain reaction (RT-PCR) of RNA from
      chondrocytes or HOAS treated with BCP crystals. MMP-13 secretion was identified
      by immunoprecipitation and MMP-1 secretion by western blot of conditioned media.
      RESULTS: BCP crystals caused a 4.5-fold increase in [3H]thymidine incorporation
      by HOAS within 20 hours compared with untreated control cultures (p< or =0.05).
      BCP crystals induced MMP-13 mRNA accumulation and MMP-13 protein secretion by
      articular chondrocytes. In contrast, in HOAS, MMP-13 mRNA induced by BCP crystals
      was detectable only by RT-PCR, and MMP-13 protein was undetectable. BCP crystals
      induced MMP-1 mRNA accumulation and MMP-1 protein secretion by HOAS. MMP-1
      expression was further augmented when HOAS were co-incubated with either BCP and
      tumour necrosis factor alpha (TNFalpha; threefold) or BCP and interleukin 1alpha
      (IL1alpha; twofold). CONCLUSION: These data confirm the ability of BCP crystals
      to activate HOAS, leading to the induction of mitogenesis and MMP-1 production.
      MMP-13 production in response to BCP crystals is substantially more detectable in
      porcine articular chondrocytes than in HOAS. These data support the active role
      of BCP crystals in osteoarthritis and suggest that BCP crystals act
      synergistically with IL1alpha and TNFalpha to promote MMP production and
      subsequent joint degeneration.

PMID- 11247874
TI  - Differentiation between primary and secondary Raynaud's phenomenon: a prospective
      study comparing nailfold capillaroscopy using an ophthalmoscope or
      stereomicroscope.
AB  - BACKGROUND: Nailfold capillary microscopy is a routine procedure in the
      investigation of patients with Raynaud's phenomenon (RP). As a standard method,
      nailfold capillary morphology is inspected with a stereomicroscope to look for
      capillary abnormalities such as giant loops, avascular areas, and bushy
      capillaries, which have all been found to be associated with certain connective
      tissue diseases. AIM: To investigate prospectively whether nailfold capillary
      inspection using an ophthalmoscope is of equivalent diagnostic value to standard
      nailfold capillary microscopy. METHOD: All the fingers of 26 patients with RP
      were examined in a blinded fashion and compared with the final diagnosis one
      month later. RESULTS: All giant loops, large avascular areas, and bushy
      capillaries were identified by both methods. The correlation for moderate
      avascular areas and crossed capillaries was 0.93 and 0.955 respectively. The
      correlation for minor abnormalities that do not contribute to the differentiation
      between primary and secondary RP was 0.837 and 0.861 respectively. All patients
      were classified identically by the two methods. CONCLUSION: For the evaluation of
      patients with RP, nailfold capillary morphology can reliably be assessed with an
      ophthalmoscope.

PMID- 11247875
TI  - A combination of etanercept and methotrexate for the treatment of refractory
      juvenile idiopathic arthritis: a pilot study.
AB  - OBJECTIVE: To study the efficacy of combination therapy with etanercept and
      methotrexate in patients with refractory juvenile idiopathic arthritis. METHODS:
      Seven children with active juvenile idiopathic arthritis refractory to at least
      combination therapy with methotrexate and sulfasalazine or cyclosporin A were
      studied. Concomitant treatment, consisting of non-steroidal drugs,
      corticosteroids, and methotrexate, remained unchanged. RESULTS: Six patients
      continued the treatment for at least 24 weeks. In the child with systemic
      arthritis, etanercept was stopped because of persisting spiking fever, joint
      pain, and rash. In the remaining children an immediate significant decrease in
      joint pain (p<0.05), disappearance of morning stiffness, and regression of joint
      swelling (p<0.05) were observed. Improvement was apparent after two injections.
      An immediate significant (p<0.05) decrease in erythrocyte sedimentation rate, C
      reactive protein, and interleukin 6 was observed. Side effects consisted of mild
      reactions at the injection site in two children. CONCLUSIONS: In this
      observational study, etanercept in combination with methotrexate was well
      tolerated and highly effective in treating juvenile polyarthritis but not in the
      patient with systemic arthritis. Combination treatment appears to be feasible in
      terms of toxicity and may enhance efficiency.

PMID- 11247877
TI  - Calcium pyrophosphatase dihydrate (CPPD) crystal deposition disease in a teaching
      hospital in Kuwait.
AB  - OBJECTIVE: A Medline electronic search showed a paucity of reports on calcium
      pyrophosphate dihydrate crystal deposition disease (CPPD-CDD) from the Gulf
      region. To date only a single case report has been published from this region.
      Therefore, this study aimed, firstly, at finding out the prevalence of
      chondrocalcinosis in adult Arabs in Kuwait presenting with knee arthritis and,
      secondly, at carrying out an observational study of CPPD-CDD among Arabs in
      Kuwait. METHODS: For the study of the prevalence of chondrocalcinosis 100
      consecutive adult patients presenting with knee arthritis were radiologically
      examined. For the observational study the clinical, laboratory, and radiological
      findings were analysed in patients with CPPD-CDD seen over a period of five
      years. RESULTS: This study showed the presence of chondrocalcinosis in two (2%)
      of the 100 adult Kuwaiti and other Middle-Eastern Arab patients (70 men, 30
      women, median age 50 (range 45-80)) who presented to the rheumatology clinic for
      the evaluation of knee pain. When the younger age of the group (only three
      patients aged >70) is taken into account the figure was comparable with that
      reported from Western countries. Over a period of five years a total of 2726 new
      patients were evaluated at the rheumatology clinic of this institution. A
      diagnosis of crystal arthritis was made in 85 patients (3%). Fourteen of these 85
      (that is, 16.5%, but 0.5% of the total cases) were diagnosed with definite (eight
      patients) or probable (six patients) CPPD-CDD. Different clinical presentations,
      including that of acute monarthritis (that is, pseudogout), premature generalised
      osteoarthritis, and polyarticular rheumatoid-like presentations, were seen in
      different patients. Overlap with true gout, with the additional presence of
      monosodium urate crystals in the joint aspirate, was seen in two patients.
      CONCLUSION: The present report shows that CPPD-CDD may not be uncommon among
      Arabs in the Gulf region. A high degree of clinical awareness and routine
      examination of joint aspirates with careful analysis for crystals may make it a
      more common diagnosis in this part of the world. In this regard it is interesting
      to note that cases and case series including familial cases have been reported
      from North Africa, especially Tunisia, indicating that the disease has been well
      described in Arabs of other geographical regions.

PMID- 11247876
TI  - Differences between female and male patients with familial rheumatoid arthritis.
AB  - OBJECTIVE: To determine whether there are genetic differences between female and
      male patients with familial rheumatoid arthritis (RA). METHODS: 45 men and 119
      women from 78 families with RA who all had at least one first degree relative
      with RA were compared. HLA-DRB1 alleles were analysed, including DRB1*04 subtypes
      and associations of DRB1*04 haplotypes with DQB1*0301 or DQB1*0302 alleles, the
      age of the patients at disease onset, the presence of rheumatoid factor (RF),
      joint erosions, and rheumatoid nodules. RESULTS: HLA-DRB1*13 allele (the subtype
      allele of DR6, reported to be protective against the development of RA) was found
      in 14/119 (12%) of female but in none of the male patients (p=0.036). The HLA-DR4
      allele was found slightly more often in men than women patients with familial RA
      (31/45 (69%) v 75/119 (63%), NS). Men were also more often RF positive than women
      (44/45 (98%) v 98/117 (84%); p=0.031). On the other hand, the mean age at onset
      of RA was significantly lower in the female group (40.4 years) than in men (46.6
      years, p=0.0044). CONCLUSION: The results indicate that there is stronger genetic
      background in familial male than female patients with RA in the genetic
      susceptibility defined by the studied HLA antigens. However, the earlier age of
      onset of the disease in female group and the increased proportion of women with
      RA indicate that there are additional sex related predisposing factors enhanced
      in familial cases.

PMID- 11247878
TI  - Type I collagen degradation does not diminish with RA disease duration.
AB  - OBJECTIVE: To assess the relation between type I collagen degradation and the
      duration of rheumatoid arthritis (RA). METHODS: The serum concentrations of cross
      linked carboxyterminal telopeptide of type I collagen (ICTP) measured earlier in
      a community based series (90 patients) and a hospital based series (59 patients)
      were re-evaluated with reference to the duration of RA. RESULTS: The serum ICTP
      showed a positive correlation with the duration of the disease in the hospital
      based series (r(s)=0.40, p<0.01) but not in the community based one (r(s)=0.18,
      p=0.10). CONCLUSIONS: Type I collagen degradation predominantly reflecting
      pathological bone destruction does not seem to diminish in longlasting RA.

PMID- 11247879
TI  - MRI guided muscle biopsy confirmed polymyositis diagnosis in a patient with
      interstitial lung disease.
AB  - Idiopathic inflammatory myopathies, such as polymyositis (PM), may present with
      general symptoms such as fever and fatigue and only minimal muscle weakness,
      making it difficult to make a definite diagnosis and provide adequate treatment.
      Here a case is described in which interstitial lung disease was the first and
      most prominent manifestation of PM. Later, when muscle weakness became apparent
      and inflammatory muscle disease was suspected the first muscle biopsy was non
      diagnostic. However, magnetic resonance imaging (MRI) scans of the clinically
      weak thigh muscles showed high signal on T(2) weighted images, suggesting muscle
      inflammation more proximal to the first biopsy site. A second biopsy at this site
      disclosed typical histopathological findings for myositis. After treatment with
      prednisolone in combination with cyclophosphamide both pulmonary and muscle
      function improved. CONCLUSION: MRI scans of muscles may be helpful in selection
      of a site for muscle biopsy in patients with suspected inflammatory myopathy when
      a first muscle biopsy turns out to be negative. Additionally, patients with
      interstitial lung disease of unknown cause should be tested for muscular function
      to exclude an associated inflammatory muscle disorder.

PMID- 11247880
TI  - Treatment of idiopathic retroperitoneal fibrosis using cyclosporin.
AB  - The main goal of traditional treatment of idiopathic retroperitoneal fibrosis is
      limitation of morbidity, and surgery of already formed fibrous masses has been
      the main therapeutic approach. More recently, the knowledge that the disorder may
      be the result of an allergic reaction to atherosclerotic lipids has prompted the
      use of corticosteroids and cytotoxic drugs, which proved efficacious, but also
      toxic. On the basis of data indicating a T cell pathogenesis of idiopathic
      retroperitoneal fibrosis, cyclosporin, a non-cytotoxic pretranscriptional
      inhibitor of proinflammatory cytokines, was used to treat the case reported here.
      A 65 year old man with aggressive retroperitoneal fibrosis and obstructive renal
      failure initially received steroids, which eventually lost their efficacy and led
      to vertebral collapse. He responded to 5 mg/kg/day cyclosporin, with radiological
      reduction of tissue deposition, relief of urether compression, and reduction in
      acute phase reactants in the blood. Chronic disease remission required stable
      drug concentrations. In conclusion, progress in research into the T cell
      pathogenesis of idiopathic retroperitoneal fibrosis may justify attempts with
      drugs such as cyclosporin to block the disease at its origin rather than treating
      the morbidity.

PMID- 11247882
TI  - Boning up on vitamin K.

PMID- 11247881
TI  - Prion proteins and the gut: une liaison dangereuse?

PMID- 11247883
TI  - Bugs and the gut: breaking barriers to understanding.

PMID- 11247885
TI  - COX-2 inhibitors and the gastrointestinal tract.

PMID- 11247886
TI  - Little benefit from mesalazine taken prophylactically after surgery for Crohn's
      disease.

PMID- 11247887
TI  - Predictive value of endoscopic ultrasonography for regression of gastric low
      grade and high grade MALT lymphomas after eradication of Helicobacter pylori.
AB  - BACKGROUND: While a close association between gastric mucosa associated lymphoid
      tissue (MALT) lymphoma and Helicobacter pylori infection has been established,
      there are still cases which do not respond to H pylori eradication. AIMS: To
      investigate the clinicopathological factors which may help predict the
      therapeutic efficacy of H pylori eradication in gastric MALT lymphoma. PATIENTS:
      Forty one patients with gastric MALT lymphoma, including low and high grade
      lesions. METHODS: After endosonographic staging was determined, H pylori was
      eradicated in all patients, and the subsequent gastric pathological course was
      then investigated. RESULTS: Complete regression of MALT lymphoma was observed in
      29(71%) patients, partial regression in five (12%), and no regression in seven
      (17%). Twenty six (93%) of 28 MALT lymphomas restricted to the mucosa but only
      three (23%) of 13 lymphomas which invaded the deep portion of the submucosa or
      beyond completely regressed. Kaplan-Meier analysis for the probability of
      complete regression of MALT lymphoma revealed a significant difference between
      tumours restricted to the mucosa and those invading the submucosa deeply or
      beyond (p<0.05). Neither the presence of a high grade component, perigastric
      lymphadenopathy, nor clinical staging prior to eradication correlated with the
      probability of lymphoma regression. CONCLUSIONS: Assessment of deep submucosal
      invasion by endosonography is valuable for predicting the efficacy of H pylori
      eradication in gastric MALT lymphoma.

PMID- 11247888
TI  - Association of the interleukin 1 receptor antagonist gene with ulcerative colitis
      in Northern European Caucasians.
AB  - BACKGROUND AND AIMS: An association between the allele 2 of the interleukin 1
      receptor antagonist gene variable number tandem repeats polymorphism in intron 2
      and ulcerative colitis was first reported in 1994. Subsequent studies in
      Caucasian Northern European patients have not confirmed this, although trends
      towards an association were observed. The lack of statistical significance could
      reflect inadequate power. In this study the association was reassessed in a large
      independent set of well characterised Caucasian patients and a meta-analysis of
      reported patient series was performed. PATIENTS AND METHODS: A total of 320
      patients with endoscopically and histologically confirmed ulcerative colitis (124
      pancolitis, 196 left sided and distal disease) and 827 ethnically matched
      controls were genotyped at polymorphic sites in the interleukin 1 receptor
      antagonist gene. Carriage rates were compared using chi(2) statistics. A meta
      analysis of this and seven previous studies in North European Caucasian patients
      was performed using the Mantel-Haenszel chi(2) test. RESULTS: Patients had a
      significantly increased carriage rate of allele 2 compared with controls (52% v
      45%; odds ratio 1.3 (95% confidence interval (CI) 1.01-1.7); p=0.04). The allele
      2 carriage rate was highest in extensive colitis (carriage rate 56%; odds ratio
      1.5 (95% CI 1.1-2.3) p=0.02) and in individuals who had undergone colectomy
      (carriage rate 55%; odds ratio 1.5 (95% CI 0.95-2.4); p=0.08). Meta-analysis of
      all eight studies showed a significant association between carriage of allele 2
      and ulcerative colitis (odds ratio 1.23 (95% CI 1.04-1.45); p=0.01). CONCLUSIONS:
      The association of the interleukin 1 receptor antagonist gene polymorphism with
      ulcerative colitis is confirmed. The association is minor and confers only a
      small risk to an individual but will contribute a high attributable risk in a
      population due to the high allelic frequency. Accurate phenotypic
      characterisation defines more homogeneous subsets of patients, such as those with
      extensive disease, in whom the association is greater.

PMID- 11247889
TI  - Neuronal COX-2 expression in human myenteric plexus in active inflammatory bowel
      disease.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is associated with changes in
      colonic motility which may contribute to the pain and diarrhoea associated with
      exacerbations of this disease. These changes may be mediated by prostaglandins
      which are increased in this condition. Increased expression of the inducible
      isoform of cyclo-oxygenase (COX-2) has been found in active IBD although its
      cellular distribution remains uncertain. AIMS: To evaluate the cellular
      distribution of COX-2 in active IBD. PATIENTS AND METHODS: Using reverse
      transcription-polymerase chain reaction, in situ hybridisation, and
      immunohistochemistry, COX-2 expression was evaluated in 12 colectomy specimens
      from patients with active ulcerative colitis (UC), and six specimens from
      patients with Crohn's colitis that had failed medical therapy. Histologically
      normal colon was obtained from 12 patients having resection for colorectal
      neoplasia and evaluated as above, acting as control specimens. RESULTS: All
      specimens expressed COX-2 mRNA, with some 6-8-fold increase in inflamed tissues
      on densitometric analysis (both UC and Crohn's) compared with controls. In situ
      hybridisation localised this mRNA to myenteric neural cells, surrounding smooth
      muscle cells, and inflammatory cells of the lamina propria in the IBD specimens,
      with some weaker labelling seen in the epithelium. No COX-2 labelling was seen in
      normal tissues. Immunohistochemistry confirmed these sites of COX-2 expression in
      all inflamed specimens, with absence of immunoreactivity in control tissues.
      CONCLUSIONS: These findings provide the first evidence of COX-2 expression in
      neural cells of the myenteric plexus in active IBD which, via increased
      prostaglandin synthesis at this site, may contribute to the dysmotilty seen in
      this condition.

PMID- 11247890
TI  - Low serum and bone vitamin K status in patients with longstanding Crohn's
      disease: another pathogenetic factor of osteoporosis in Crohn's disease?
AB  - BACKGROUND: A high prevalence of osteoporosis is reported in Crohn's disease. The
      pathogenesis is not completely understood but is probably multifactorial.
      Longstanding Crohn's disease is associated with a deficiency of fat soluble
      vitamins, among them vitamin K. Vitamin K is a cofactor in the carboxylation of
      osteocalcin, a protein essential for calcium binding to bone. A high level of
      circulating uncarboxylated osteocalcin is a sensitive marker of vitamin K
      deficiency. AIMS: To determine serum and bone vitamin K status in patients with
      Crohn's disease and to elucidate its relationship with bone mineral density.
      METHODS: Bone mineral density was measured in 32 patients with longstanding
      Crohn's disease and small bowel involvement, currently in remission, and
      receiving less than 5 mg of prednisolone daily. Serum levels of vitamins D and K,
      triglycerides, and total immunoreactive osteocalcin, as well as uncarboxylated
      osteocalcin ("free" osteocalcin) were determined. The hydroxyapatite binding
      capacity of osteocalcin was calculated. Data were compared with an age and sex
      matched control population. RESULTS: Serum vitamin K levels of CD patients were
      significantly decreased compared with normal controls (p<0.01). "Free"
      osteocalcin was higher and hydroxyapatite binding capacity of circulating
      osteocalcin was lower than in matched controls (p<0.05 and p<0.001,
      respectively), indicating a low bone vitamin K status in Crohn's disease. In
      patients, an inverse correlation was found between "free" osteocalcin and lumbar
      spine bone mineral density (r=-0.375, p<0.05) and between "free" osteocalcin and
      the z score of the lumbar spine (r=-0.381, p<0.05). Multiple linear regression
      analysis showed that "free" osteocalcin was an independent risk factor for low
      bone mineral density of the lumbar spine whereas serum vitamin D was not.
      CONCLUSIONS: The finding that a poor vitamin K status is associated with low bone
      mineral density in longstanding Crohn's disease may have implications for the
      prevention and treatment of osteoporosis in this disorder.

PMID- 11247892
TI  - Role of T lymphocytes in rat 2,4,6-trinitrobenzene sulphonic acid (TNBS) induced
      colitis: increased mortality after gammadelta T cell depletion and no effect of
      alphabeta T cell depletion.
AB  - BACKGROUND AND AIM: Indirect evidence suggests that CD4+ T cells have a
      pathogenic while gammadelta T cells have a protective role in the initiation and
      perpetuation of inflammatory bowel disease. To define the role of T cell subsets
      in a rat colitis model (2,4,6-trinitrobenzene sulphonic acid (TNBS)) we analysed
      colitis severity after effective depletion of T helper cells, alphabeta T cells,
      or gammadelta T cells. METHODS: T helper cells, alphabeta T cells, or gammadelta
      T cells were depleted using previously described monoclonal antibodies directed
      at the CD4 molecule (OX38), the CD2 molecule (OX34, both depleting CD4+ T cells),
      the alphabeta T cell receptor (R73), and the gammadelta T cell receptor (V65).
      Depletion was verified by flow cytometry and/or immunohistology. Colitis was
      induced using intracolonic application of TNBS. RESULTS: Surprisingly, depletion
      of T helper cells or alphabeta T cells had no influence on survival, macroscopic
      or microscopic scores, or myeloperoxidase activity following colitis induction.
      In contrast, depletion of gammadelta T cells resulted in significantly increased
      mortality (V65: 73%, n=15) compared with controls (30%, n=13; p<0.03). In
      addition, colitis was histologically more severe in the gammadelta T cell
      depleted group compared with controls (p<0.05). CONCLUSIONS: T helper cells or
      alphabeta T cells did not influence the initiation or perpetuation of rat TNBS
      colitis. In contrast, gammadelta T cells had a protective role in rat TNBS
      colitis as depletion caused increased mortality.

PMID- 11247894
TI  - Modulation of colonic barrier function by the composition of the commensal flora
      in the rat.
AB  - BACKGROUND AND AIMS: Altered intestinal permeability is a key pathogenetic factor
      of idiopathic bowel inflammation. We investigated in the rat if changes in the
      composition of the bowel flora can alter colonic permeability. METHODS: A colonic
      segment was surgically excluded from faecal transit and brought out as a loop to
      the abdominal wall through two colostomies. The loop was used for colonisation
      with specific bacterial strains after eradication of the native flora with
      antibiotics. Lumen to blood clearance of dextran (molecular weight 70 000) and
      mannitol (molecular weight 182) was measured in rats recolonised with a single
      bacterial strain from rat colonic origin, and in control rats whose colonic loop
      was kept free of bacteria by antibiotics. Actual colonisation was confirmed by
      culture of segment effluents. RESULTS: Colonisation with Escherichia coli,
      Klebsiella pneumoniae, and Streptococcus viridans significantly increased lumen
      to blood clearance of mannitol. Colonisation with Lactobacillus brevis had the
      opposite effect and reduced permeability to mannitol. Bacteroides fragilis did
      not induce significant changes. Permeability to dextran was not altered by any of
      the strains tested. CONCLUSIONS: Certain commensal bacteria can modify colonic
      wall permeability to luminal substances.

PMID- 11247891
TI  - Calpain inhibitor I reduces colon injury caused by dinitrobenzene sulphonic acid
      in the rat.
AB  - BACKGROUND AND AIMS: Inflammatory bowel disease is characterised by oxidative and
      nitrosative stress, leucocyte infiltration, upregulation of expression of
      intercellular adhesion molecule 1 (ICAM-1), and upregulation of P-selectin in the
      colon. The aim of the present study was to examine the effects of calpain
      inhibitor I in rats subjected to experimental colitis. METHODS: Colitis was
      induced in rats by intracolonic instillation of dinitrobenzene sulphonic acid
      (DNBS). RESULTS: Rats experienced haemorrhagic diarrhoea and weight loss. Four
      days after administration of DNAB, the mucosa of the colon exhibited large areas
      of necrosis. Neutrophil infiltration (determined by histology as well as by an
      increase in myeloperoxidase activity in the mucosa) was associated with
      upregulation of ICAM-1 and P-selectin as well as high tissue levels of
      malondialdehyde. Immunohistochemistry for nitrotyrosine and poly (ADP-ribose)
      polymerase (PARP) showed intense staining in the inflamed colon. Staining of
      sections of colon obtained from DNBS treated rats with an anti-cyclooxygenase 2
      antibody showed diffuse staining of the inflamed tissue. Furthermore, expression
      of inducible nitric oxide synthase was found mainly in macrophages located within
      the inflamed colon of DNBS treated rats. Calpain inhibitor I (5 mg/kg daily
      intraperitoneally) significantly reduced the degree of haemorrhagic diarrhoea and
      weight loss caused by administration of DNBS. Calpain inhibitor I also caused a
      substantial reduction in (i) degree of colon injury, (ii) rise in myeloperoxidase
      activity (mucosa), (iii) increase in tissue levels of malondialdehyde, (iv)
      increase in staining (immunohistochemistry) for nitrotyrosine and PARP, as well
      as (v) upregulation of ICAM-1 and P-selectin caused by DNBS in the colon.
      CONCLUSION: Calpain inhibitor I reduces the degree of colitis caused by DNBS. We
      propose that calpain inhibitor I may be useful in the treatment of inflammatory
      bowel disease.

PMID- 11247893
TI  - Parallel expression of macrophage metalloelastase (MMP-12) in duodenal and skin
      lesions of patients with dermatitis herpetiformis.
AB  - BACKGROUND: Dermatitis herpetiformis (DH) is a specific dermatological
      manifestation of coeliac disease and 80% of DH patients have gluten sensitive
      enteropathy manifested by crypt hyperplasia and villous atrophy. Matrix
      degradation mediated by collagenase 1 (MMP-1) and stromelysin 1 (MMP-3) has
      previously been implicated in the pathobiology of coeliac intestine and cutaneous
      DH blisters. AIMS: To study expression of stromelysin 2, metalloelastase,
      collagenase 3, and matrilysin in the intestine and skin of DH patients. METHODS:
      In situ hybridisation using 35S labelled cRNA probes was performed on duodenal
      biopsies of 15 DH patients, three samples each of control duodenal or jejunal
      mucosa, fetal ileal explants, lesional DH skin, and 19 serial biopsies of
      experimental DH blisters. Immunostaining was used to examine type IV collagen,
      macrophages (CD68), and 92 kDa gelatinase (MMP-9) in the specimens. RESULTS:
      Metalloelastase (MMP-12) was abundantly expressed by subepithelial macrophages in
      both coeliac intestine and spontaneous and induced DH rash. It was also
      upregulated in the experimental model of coeliac disease (staphylococcal
      endotoxin B stimulated fetal explants). The only other MMP detected was MMP-9
      which did not colocalise with MMP-12. CONCLUSIONS: Upregulation of
      metalloelastase is associated with T cell mediated immune responses both in the
      intestine and skin. In addition to modulating macrophage migration, it may
      contribute to degradation of proteoglycans or basement membrane components in the
      subepithelial mucosa.

PMID- 11247895
TI  - Familial adenomatous polyposis: more evidence for disease diversity and genetic
      heterogeneity.
AB  - Familial adenomatous polyposis (FAP) is characterised by the presence of profuse
      colonic carpeting of adenomas throughout the entire colon and rectum. The genetic
      basis of FAP has been shown to be primarily associated with germline mutations in
      the APC gene. Notwithstanding, several reports have been published indicating
      that there is genetic heterogeneity in FAP and that the most likely explanation
      is the existence of another gene. In this report we further delineate the
      genotype/phenotype correlation in families that harbour germline mutations in the
      APC gene and identify some previously unreported changes in the APC gene which
      predispose to an attenuated disease phenotype. From 53 index patients diagnosed
      with either FAP or attenuated FAP, 27 harboured changes in the APC gene. The
      remaining 26 patients were further subgrouped according to their colonic
      phenotype. There were nine patients with a mixed hyperplastic/adenomatous colonic
      phenotype and there were 17 patients with an adenomatous colonic phenotype.
      Evaluation of the disease characteristics of these patients and their families is
      presented which may aid in the identification of new genes associated with
      colonic polyposis.

PMID- 11247896
TI  - Can APC mutation analysis contribute to therapeutic decisions in familial
      adenomatous polyposis? Experience from 680 FAP families.
AB  - BACKGROUND AND AIMS: In familial adenomatous polyposis (FAP), correlations
      between site of mutation in the adenomatous polyposis coli (APC) gene and
      severity of colonic polyposis or extracolonic manifestations are well known.
      While mutation analysis is important for predictive diagnosis in persons at risk,
      its relevance for clinical management of individual patients is open to question.
      METHODS: We examined 680 unrelated FAP families for germline mutations in the APC
      gene. Clinical information was obtained from 1256 patients. RESULTS: APC
      mutations were detected in 48% (327/680) of families. Age at diagnosis of FAP
      based on bowel symptoms and age at diagnosis of colorectal cancer in untreated
      patients were used as indicators of the severity of the natural course of the
      disease. A germline mutation was detected in 230 of 404 patients who were
      diagnosed after onset of bowel symptoms (rectal bleeding, abdominal pain,
      diarrhoea). When these patients were grouped according to the different sites of
      mutations, mean values for age at onset of disease differed significantly:
      patients carrying APC mutations at codon 1309 showed a disease onset 10 years
      earlier (mean age 20 years) compared with patients with mutations between codons
      168 and 1580 (except codon 1309) (mean age 30 years), whereas patients with
      mutations at the 5' end of codon 168 or the 3' end of codon 1580 were diagnosed
      at a mean age of 52 years. Within each group of patients however large phenotypic
      variation was observed, even among patients with identical germline mutations. A
      higher incidence of desmoids was found in patients with mutations between codons
      1445 and 1580 compared with mutations at other sites, while no correlation
      between site of mutation and presence of duodenal adenomas was observed.
      CONCLUSIONS: As age at manifestation and course of the disease may be rather
      variable, even in carriers of identical germline mutations, therapeutic decisions
      should be based on colonoscopic findings in individual patients rather than on
      the site of mutation. However, in patients with mutations within codons 1445
      1580, it may be advisable to postpone elective colectomy because desmoids may
      arise through surgical intervention.

PMID- 11247897
TI  - Flexible sigmoidoscopy and the changing distribution of colorectal cancer:
      implications for screening.
AB  - BACKGROUND AND AIMS: There has been a significant proximal shift in the
      distribution of colorectal cancer (CRC) in Northern Ireland over recent decades.
      The aim of this study was to investigate the potential implications of this
      proximal shift in CRC distribution on the efficacy of flexible sigmoidoscopy (FS)
      as a screening tool. PATIENTS AND METHODS: The site distribution of 5153 CRCs was
      available from the Northern Ireland Colorectal Cancer Register for the period
      1990-1997. Similar data on 1241 CRCs between 1976 and 1978 were available from a
      previous study. Data on the site reached by FS were obtained from a prospectively
      collected endoscopy database at one of Northern Ireland's main teaching hospitals
      for the period 1993-1998. RESULTS: There was a significant proximal shift in CRC
      distribution between the two periods (23.5% proximal to the splenic flexure
      between 1976 and 1978 v 36.7% between 1990 and 1997; p<0.001). The descending
      colon was visualised during 74.4% of FS examinations. By combining the observed
      extent of FS examination with CRC site distribution, it was calculated that FS
      could have visualised 68.8% of CRCs between 1976 and 1978 but only 56.0% between
      1990 and 1997. Extrapolating these data to a Northern Ireland screening programme
      involving FS and faecal occult blood testing suggests that significantly more
      CRCs could have been detected between 1976 and 1978 than between 1990 and 1997
      (51.7% v 48.2%, respectively; p=0.03). CONCLUSIONS: This study confirms the
      previously documented left to right shift in CRC distribution in Northern Ireland
      and demonstrates that if this shift continues, FS will become less successful as
      a screening tool than is currently predicted.

PMID- 11247899
TI  - Analysis of sporadic neuroendocrine tumours of the enteropancreatic system by
      comparative genomic hybridisation.
AB  - BACKGROUND: Chromosomal instability is observed in a wide spectrum of human
      cancer syndromes. However, to date, little is known of the characteristic genetic
      changes in sporadic neuroendocrine tumours of the gastroenteropancreatic system.
      AIMS AND METHOD: We have studied copy number aberrations (CNAs) in 26 sporadic
      neuroendocrine tumours of the enteropancreatic system (12 foregut and 14 midgut
      tumours) by comparative genomic hybridisation (CGH), allowing simultaneous
      evaluation of the entire tumour genome. RESULTS: Nearly all tumours (25/26; that
      is, 96%) showed chromosomal imbalances, including full chromosomal aneuploidies,
      losses and gains of chromosome arms, interstitial deletions, and amplifications.
      Whereas gains of chromosomes 4, 5, and 19 were found in both foregut and midgut
      tumours, gains of chromosomes 20q (58%), 19 (50%), as well as 17p (50%), and
      partial losses of chromosomes 1p (42%), 2q (42%), 3p, 4q, and 6q (25% each) were
      frequently observed only in foregut tumours. In contrast, midgut tumours
      displayed less CNAs. Gains were detected for chromosomes 17q and 19p (57%). Most
      frequent losses affected chromosomes 18 (43%) and 9p (21%). CONCLUSIONS: The
      results of our CGH analyses revealed new distinct candidate regions in the human
      genome associated with sporadic neuroendocrine tumours. Some of the genetic
      alterations were shared by foregut and midgut tumours while others discriminated
      between the two groups. Thus our results allude to the involvement of identical
      as well as discriminative genetic loci in tumorigenesis and progression of
      neuroendocrine neoplasms of the foregut and midgut. Based on these findings
      potential new candidate genes will be discussed.

PMID- 11247900
TI  - Expression and penetrance of the hereditary pancreatitis phenotype in monozygotic
      twins.
AB  - BACKGROUND: Hereditary pancreatitis (HP) is a rare autosomal dominant disorder
      with variable expression and an overall lifetime penetrance of 80%. We
      hypothesised that (1) monozygotic twins within similar environments would develop
      the typical signs of HP at a similar age, and (2) if penetrance were due to
      modifier genes or environment, all twin pairs would be concordant for expression
      of HP. AIM: Identify monozygotic twins with HP and determine the penetrance,
      concordance, and age of onset of symptoms. METHODS: Twins from HP kindreds were
      identified from the Midwest Multicenter Pancreatic Study group database,
      referrals, and literature searches. Each twin set was assessed for phenotypic
      expression, concordance, and difference in age of phenotypic onset of
      pancreatitis. The difference in onset of symptoms for symptomatic affected non
      twin sibling pairs as well as non-twin pairs that were mutation, sex, and age
      matched were calculated as two comparison groups. RESULTS: Seven of 11
      monozygotic pairs identified were suitable for evaluation and four were
      concordant for pancreatitis. Forty eight affected sibling pairs and 33 pairs of
      mutation, sex, and age matched (cationic trypsinogen R122H (30 pairs) and N29I
      (three pairs)) subjects were identified for comparison groups. The median
      (quartiles Q1, Q3) difference in the age of phenotypic onset in the concordant
      twins was 1 (0, 2.4) years, 2 (1, 6) for the affected siblings, and 7 (2, 15)
      years in the comparison control group. Three of the seven sets of twins (43%)
      were discordant for phenotypic expression of pancreatitis. The overall penetrance
      in the seven pairs of monozygotic twins was 78.6%. CONCLUSIONS: Genetic and/or
      environmental factors contribute to expression and age of onset of HP. Nuclear
      genes or general environmental factors alone cannot explain the 80% penetrance.
      Determining the mechanism of non-penetrance may help in developing a strategy to
      prevent the phenotypic expression of pancreatitis in individuals with an
      underlying genetic predisposition.

PMID- 11247901
TI  - Apoptosis of hepatic stellate cells: involvement in resolution of biliary
      fibrosis and regulation by soluble growth factors.
AB  - BACKGROUND: Activated hepatic stellate cells (HSC) are central to the
      pathogenesis of liver fibrosis, both as a source of fibrillar collagens that
      characterise fibrosis and matrix degrading metalloproteinases and their tissue
      inhibitors, the TIMPs. AIMS: To test the hypothesis that HSC apoptosis is
      critical to recovery from biliary fibrosis and that soluble growth factors may
      regulate HSC survival and apoptosis. METHODS: Rats (n=15) were subjected to bile
      duct ligation for 21 days, after which biliodigestive anastomosis was undertaken
      (n=13). Livers were harvested at fixed time points of recovery for periods of up
      to 42 days. Numbers of activated HSCs were quantified after alpha smooth muscle
      actin staining and HSC apoptosis was detected by terminal UDP-nick end labelling
      (TUNEL) staining and quantified at each time point. HSC apoptosis was quantified
      in vitro in the presence or absence of insulin-like growth factor (IGF)-1, IGF-2,
      platelet derived growth factor (PDGF), and transforming growth factor beta1 (TGF
      beta1). RESULTS: Following biliodigestive anastomosis after 21 days of bile duct
      ligation, rat liver demonstrated a progressive resolution of biliary fibrosis
      over 42 days, associated with a fivefold decrease in activated HSC determined by
      alpha smooth muscle actin staining. TUNEL staining indicated that loss of
      activated HSC resulted from an increase in the rate of apoptosis during the first
      two days post biliodigestive anastomosis. Serum deprivation and culture in the
      presence of 50 microM cycloheximide was associated with an increase in HSC
      apoptosis which was significantly inhibited by addition of 10 ng/ml and 100 ng/ml
      IGF-1, respectively (0.05>p, n=5). In contrast, 1 and 10 ng/ml of TGF-beta1
      caused a significant increase in HSC apoptosis compared with serum free controls
      (p<0.05, n=4). PDGF and IGF-2 were neutral with respect to their effect on HSC
      apoptosis. CONCLUSION: HSC apoptosis plays a critical role in the spontaneous
      recovery from biliary fibrosis. Both survival and apoptosis of HSC are regulated
      by growth factors expressed during fibrotic liver injury.

PMID- 11247898
TI  - The risk of colorectal cancer in ulcerative colitis: a meta-analysis.
AB  - BACKGROUND AND AIMS: Controversy surrounds the risk of colorectal cancer (CRC) in
      ulcerative colitis (UC). Many studies have investigated this risk and reported
      widely varying rates. METHODS: A literature search using Medline with the
      explosion of references identified 194 studies. Of these, 116 met our inclusion
      criteria from which the number of patients and cancers detected could be
      extracted. Overall pooled estimates, with 95% confidence intervals (CI), of
      cancer prevalence and incidence were obtained using a random effects model on
      either the log odds or log incidence scale, as appropriate. RESULTS: The overall
      prevalence of CRC in any UC patient, based on 116 studies, was estimated to be
      3.7% (95% CI 3.2-4.2%). Of the 116 studies, 41 reported colitis duration. From
      these the overall incidence rate was 3/1000 person years duration (pyd), (95% CI
      2/1000 to 4/1000). The overall incidence rate for any child was 6/1000 pyd (95%
      CI 3/1000 to 13/1000). Of the 41 studies, 19 reported results stratified into 10
      year intervals of disease duration. For the first 10 years the incidence rate was
      2/1000 pyd (95% CI 1/1000 to 2/1000), for the second decade the incidence rate
      was estimated to be 7/1000 pyd (95% CI 4/1000 to 12/1000), and in the third
      decade the incidence rate was 12/1000 pyd (95% CI 7/1000 to 19/1000). These
      incidence rates corresponded to cumulative probabilities of 2% by 10 years, 8% by
      20 years, and 18% by 30 years. The worldwide cancer incidence rates varied
      geographically, being 5/1000 pyd in the USA, 4/1000 pyd in the UK, and 2/1000 pyd
      in Scandinavia and other countries. Over time the cancer risk has increased since
      1955 but this finding was not significant (p=0.8). CONCLUSIONS: Using new meta
      analysis techniques we determined the risk of CRC in UC by decade of disease and
      defined the risk in pancolitics and children. We found a non-significant increase
      in risk over time and estimated how risk varies with geography.

PMID- 11247903
TI  - Ultrasound appearance of preclinical Oesophagostomum bifurcum induced colonic
      pathology.

PMID- 11247902
TI  - Enhanced glypican-3 expression differentiates the majority of hepatocellular
      carcinomas from benign hepatic disorders.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is a common malignant tumour
      worldwide, and its differential diagnosis from benign lesions of the liver is
      often difficult yet of great clinical importance. In the present study, we
      analysed whether glypican-3 is useful in differentiating between benign and
      malignant liver diseases and whether it influences the growth behaviour of HCC.
      METHODS: Northern blot analysis and in situ hybridisation. RESULTS: Northern blot
      analysis indicated that expression of glypican-3 mRNA was either low or absent in
      normal liver, in focal nodular hyperplasia (FNH), and in liver cirrhosis. In
      contrast, expression of glypican-3 mRNA was markedly increased in 20 of 30 and
      moderately increased in five of 30 HCC samples. The average increase in glypican
      3 mRNA expression in HCC was significant compared with expression in normal liver
      (21.7-fold increase, p<0.01). In comparison with FNH or liver cirrhosis, glypican
      3 mRNA expression in HCC was increased 7.2- (p<0.05) and 10.8-fold (p<0.01),
      respectively. In addition, pushing HCCs exhibited significantly higher glypican-3
      mRNA expression than invading tumours (p<0.05). In situ hybridisation analysis
      demonstrated weak expression of glypican-3 mRNA in normal hepatocytes and bile
      ductular cells, and weak to occasionally moderate signals in hepatocytes forming
      nodules of liver cirrhosis and in regenerated hepatic nodules of FNH. In
      contrast, glypican-3 in situ hybridisation signals were intense in hepatic cancer
      cells with even higher levels in pushing HCCs than in invading HCCs. CONCLUSIONS:
      These findings suggest that glypican-3, in many cases, has the potential to
      differentiate between benign and malignant liver diseases.

PMID- 11247904
TI  - Search and treat strategy to eliminate Helicobacter pylori associated ulcer
      disease.

PMID- 11247913
TI  - Respiratory control in humans after 8 h of lowered arterial PO2, hemodilution, or
      carboxyhemoglobinemia.
AB  - In humans exposed to 8 h of isocapnic hypoxia, there is a progressive increase in
      ventilation that is associated with an increase in the ventilatory sensitivity to
      acute hypoxia. To determine the relative roles of lowered arterial PO2 and oxygen
      content in generating these changes, the acute hypoxic ventilatory response was
      determined in 11 subjects after four 8-h exposures: 1) protocol IH (isocapnic
      hypoxia), in which end-tidal PO2 was held at 55 Torr and end-tidal PCO2 was
      maintained at the preexposure value; 2) protocol PB (phlebotomy), in which 500 ml
      of venous blood were withdrawn; 3) protocol CO, in which carboxyhemoglobin was
      maintained at 10% by controlled carbon monoxide inhalation; and 4) protocol C as
      a control. Both hypoxic sensitivity and ventilation in the absence of hypoxia
      increased significantly after protocol IH (P < 0.001 and P < 0.005, respectively,
      ANOVA) but not after the other three protocols. This indicates that it is the
      reduction in arterial PO2 that is primarily important in generating the increase
      in the acute hypoxic ventilatory response in prolonged hypoxia. The associated
      reduction in arterial oxygen content is unlikely to play an important role.

PMID- 11247905
TI  - Intestinal luminal pH in inflammatory bowel disease: possible determinants and
      implications for therapy with aminosalicylates and other drugs.
AB  - Measurements of luminal pH in the normal gastrointestinal tract have shown a
      progressive increase in pH from the duodenum to the terminal ileum, a decrease in
      the caecum, and then a slow rise along the colon to the rectum. Some data in
      patients with ulcerative colitis suggest a substantial reduction below normal
      values in the right colon, while limited results in Crohn's disease have been
      contradictory. Determinants of luminal pH in the colon include mucosal
      bicarbonate and lactate production, bacterial fermentation of carbohydrates and
      mucosal absorption of short chain fatty acids, and possibly intestinal transit.
      Alterations in these factors, as a result of mucosal disease and changes in diet,
      are likely to explain abnormal pH measurements in inflammatory bowel disease
      (IBD). It is conceivable that reduced intracolonic pH in active ulcerative
      colitis impairs bioavailability of 5-aminosalicylic acid from pH dependent
      release formulations (Asacol, Salofalk) and those requiring cleavage by bacterial
      azo reductase (sulphasalazine, olsalazine, balsalazide), but further
      pharmacokinetic studies are needed to confirm this possibility. Reports that
      balsalazide and olsalazine may be more efficacious in active and quiescent
      ulcerative colitis, respectively, than Asacol suggest that low pH may be a more
      critical factor in patients taking directly pH dependent release than azo bonded
      preparations. Reduced intracolonic pH also needs to be considered in the
      development of pH dependent colonic release formulations of budesonide and
      azathioprine for use in ulcerative and Crohn's colitis. This paper reviews
      methods for measuring gut pH, its changes in IBD, and how these may influence
      current and future therapies.

PMID- 11247914
TI  - Effect of unilateral denervation on maximum specific force in rat diaphragm
      muscle fibers.
AB  - We hypothesize that 1) the effect of denervation (DNV) is more pronounced in
      fibers expressing fast myosin heavy chain (MHC) isoforms and 2) the effect of DNV
      on maximum specific force reflects a reduction in MHC content per half sarcomere
      or the number of cross bridges in parallel. Studies were performed on single
      Triton X-100-permeabilized fibers activated at a pCa (-log Ca2+ concentration) of
      4.0. MHC content per half sarcomere was determined by densitometric analysis of
      SDS-PAGE gels and comparison to a standard curve of known MHC concentrations.
      After 2 of wk DNV, the maximum specific force of fibers expressing MHC2X was
      reduced by approximately 40% (MHC(2B) expression was absent), whereas the maximum
      specific force of fibers expressing MHC2A and MHC(slow) decreased by only
      approximately 20%. DNV also reduced the MHC content in fibers expressing MHC2X,
      with no effect on fibers expressing MHC2A and MHC(slow). When normalized for MHC
      content per half sarcomere, force generated by DNV fibers expressing MHC2X and
      MHC2A was decreased compared with control fibers. These results suggest the force
      per cross bridge is also affected by DNV.

PMID- 11247915
TI  - CNTF genotype is associated with muscular strength and quality in humans across
      the adult age span.
AB  - The relationship between ciliary neurotrophic factor (CNTF) genotype and muscle
      strength was examined in 494 healthy men and women across the entire adult age
      span (20-90 yr). Concentric (Con) and eccentric (Ecc) peak torque were assessed
      using a Kin-Com isokinetic dynamometer for the knee extensors (KE) and knee
      flexors (KF) at slow (0.52 rad/s) and faster (3.14 rad/s) velocities. The results
      were covaried for age, gender, and body mass or fat-free mass (FFM). Individuals
      heterozygous for the CNTF null (A allele) mutation (G/A) exhibited significantly
      higher Con peak torque of the KE and KF at 3.14 rad/s than G/G homozygotes when
      age, gender, and body mass were covaried (P < 0.05). When the dominant leg FFM
      (estimated muscle mass) was used in place of body mass as a covariate, Con peak
      torque of the KE at 3.14 rad/s was also significantly greater in the G/A
      individuals (P < 0.05). In addition, muscle quality of the KE (peak torque at
      3.14 rad x s(-1) x leg muscle mass(-1)) was significantly greater in the G/A
      heterozygotes (P < 0.05). Similar results were seen in a subanalysis of subjects
      60 yr and older, as well as in Caucasian subjects. In contrast, A/A homozygotes
      demonstrated significantly lower Ecc peak torque at 0.52 rad/s for both KE and KF
      compared with G/G and G/A groups (P < 0.05). No significant relationships were
      observed at 0.52 rad/s between genotype and Con peak torque. These data indicate
      that individuals exhibiting the G/A genotype possess significantly greater
      muscular strength and muscle quality at relatively fast contraction speeds than
      do G/G individuals. Because of high positive correlations between fast-velocity
      peak torque and muscular power, these findings suggest that further
      investigations should address the relationship between CNTF genotype and muscular
      power.

PMID- 11247918
TI  - Hormonal regulation of PGE2 and COX-2 production in rabbit uterine cervical
      fibroblasts.
AB  - Prostaglandins (PGs) cause uterine contraction to initiate labor at term. We
      investigated the effect of progesterone and 17beta-estradiol on the production of
      PGE2 in rabbit uterine cervical fibroblasts. When the cervical fibroblasts were
      treated with interleukin-1alpha (IL-1alpha), the level of PGE2 was augmented in a
      time- and dose-dependent manner. The IL-1alpha-augmented PGE2 level was almost
      completely suppressed by progesterone and 17beta-estradiol at the physiological
      concentration (0.01 microM), whereas a slight decrease in the basal level of PGE2
      was observed in the cervical fibroblasts treated with both hormones at a
      pharmacological concentration (1 microM). In addition, the level of PGE2
      augmented by IL-1alpha was due to the increase of cyclooxygenase (COX) activity,
      which was inhibited by progesterone and 17beta-estradiol as well as by
      indomethacin and a specific COX-2 inhibitor, NS-398, but not by the well-known
      COX-1 inhibitor, aspirin. Furthermore, progesterone and 17beta-estradiol
      suppressed the IL-1alpha-augmented COX-2 production but not the constitutive
      production of COX-1 in rabbit uterine cervical fibroblasts. These results suggest
      that progesterone and 17beta-estradiol prevent the initiation of labor by
      inhibiting PGE2 production after the suppression of COX-2 production during
      pregnancy in the rabbit.

PMID- 11247917
TI  - Effect of short-term exercise training on angiogenic growth factor gene responses
      in rats.
AB  - We investigated whether 1) 5 days of exercise training would reduce the acute
      exercise-induced increase in skeletal muscle growth factor gene expression; and
      2) reductions in the increase in growth factor gene expression in response to
      short-term exercise training would be coincident with increases in skeletal
      muscle oxidative potential. Female Wistar rats were used. Six groups (rest;
      exercise for 1-5 consecutive days) were used to measure the growth factor
      response through the early phases of an exercise training program. Vascular
      endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1),
      and basic fibroblast growth factor (bFGF) mRNA were analyzed from the left
      gastrocnemius by quantitative Northern blot. Citrate synthase activity was
      analyzed from the right gastrocnemius. VEGF and TGF-beta1 mRNA increased after
      each of 5 days of exercise training, whereas exercise on any day did not increase
      bFGF mRNA. On day 1, the VEGF mRNA response was significantly greater than on
      days 2-5. However, the reduced increase in VEGF mRNA observed on days 2-5 was not
      coincident with increases in citrate synthase activity. These findings suggest
      that, in skeletal muscle, 1) VEGF and TGF-beta1 mRNA are increased through 5 days
      of exercise training and 2) the reduced exercise-induced increase in VEGF mRNA
      responses on days 2-5 does not result from increases in oxidative potential.

PMID- 11247916
TI  - Habituation of thermal sensations, skin temperatures, and norepinephrine in men
      exposed to cold air.
AB  - We studied habituation processes by exposing six healthy men to cold air (2 h in
      a 10 degrees C room) daily for 11 days. During the repeated cold exposures, the
      general cold sensations and those of hand and foot became habituated so that they
      were already significantly less intense after the first exposure and remained
      habituated to the end of the experiment. The decreases in skin temperatures and
      increases in systolic blood pressure became habituated after four to six
      exposures, but their habituations occurred only at a few time points during the
      120-min cold exposure and vanished by the end of the exposures. Serum thyroid
      stimulating hormone, total thyroxine and triiodothyronine, norepinephrine,
      epinephrine, cortisol, and total proteins were measured before and after the 120
      min cold exposure on days 0, 5, and 10. The increase in norepinephrine response
      became reduced on days 5 and 10 and that of proteins on day 10, suggesting that
      the sympathetic nervous system became habituated and hemoconcentration became
      attenuated. Thus repeated cold-air exposures lead to habituations of cold
      sensation and norepinephrine response and to attenuation of hemoconcentration,
      which provide certain benefits to those humans who have to stay and work in cold
      environments.

PMID- 11247919
TI  - Angiogenin gene-race interaction for resting and exercise BP phenotypes: the
      HERITAGE Family Study.
AB  - We examined the association between an angiogenin gene polymorphism and blood
      pressure (BP) at rest and in response to acute exercise before and after a 20-wk
      endurance-training program. Subjects were 737 normotensive and borderline
      hypertensive subjects (257 black and 480 white). The polymorphism was detected by
      PCR and digestion with AvaII, yielding an allele of 253 bp or a rare allele of
      194 + 59 bp. Resting and exercise [50 W; 60, 80, and 100% of maximal O2
      consumption (VO2 max)] systolic (SBP) and diastolic BP were determined before and
      after training. Among blacks, adjusted SBP in the sedentary state was
      significantly lower in carriers of the rare allele at rest and exercise
      intensities of 60, 80, and 100% of VO2 max. In the trained state, carriers of the
      rare allele had a significantly (P < 0.05) lower SBP than did noncarriers at rest
      and at 80 and 100% of VO2 max. The genotypic effect observed among blacks was not
      evident among whites. Furthermore, change in BP (after--before) was not
      significantly associated with the genotype. In conclusion, the angiogenin gene
      AvaII polymorphism is associated with a lower SBP at rest and in response to
      acute high-intensity exercise in blacks but not in whites.

PMID- 11247920
TI  - Effect of exercise and medium-chain fatty acids on postprandial lipemia.
AB  - The purpose of this study was to evaluate the effect of medium-chain
      triglycerides (MCT) with and without exercise on postprandial lipemia (PPL).
      Subjects were 25 young men and women. Each subject performed three trials: 1)
      control (fat meal only, 1.5 g fat/kg) 2) MCT (substitution of MCT oil, 30% of fat
      calories), and 3) MCT + Ex (exercise 12 h before the MCT meal). Before each
      trial, the subject underwent consistent dietary preparation. Blood was collected
      on 2 separate days for baseline measurements of postheparin lipases and, in each
      trial, at 0 h (premeal), at 2, 4, 6, and 8 h after the fat meal for triglycerides
      and cholesterol ester transfer protein (CETP), and at 8 h for postheparin
      lipoprotein lipase (LPL) and hepatic lipase activities (HL). ANOVA indicated that
      the partial substitution of MCT oil to the fat meal did not affect the PPL
      response. However, the PPL was significantly lower after the MCT + Ex trial vs.
      the other trials. LPL activity was significantly elevated after all trials
      compared with baseline, whereas HL was lower in the MCT + Ex trial only. CETP
      mass was significantly lower at 4 and 8 h than 0 h during all trials but
      relatively higher in the MCT + Ex trial vs. the nonexercise trials. These results
      suggest that MCT does not affect the TG response to a fat meal. LPL and CETP are
      affected by a fat meal with or without exercise, but HL is affected only when
      exercise is included.

PMID- 11247921
TI  - CO2 dialysis in the medullary raphe of the rat increases ventilation in sleep.
AB  - Central chemoreceptors are widespread within the brain stem. We hypothesize that
      function at different sites varies with arousal state. In unanesthetized rats, we
      produced focal acidification at single sites by means of microdialysis using
      artificial cerebrospinal fluid equilibrated with 25% CO2. Tissue acidosis,
      measured under anesthesia, is equivalent to that observed with 63 Torr end-tidal
      PCO2 and is limited to 600 microm. Focal acidification of the retrotrapezoid
      nucleus increased ventilation by 24% only in wakefulness via an increase in tidal
      volume (Li A, Randall M, and Nattie E. J Appl Physiol 87: 910-919, 1999). In this
      study of the medullary raphe, the effect of such focal acidification was in sleep
      (defined by electroencephalographic and electromyographic criteria): ventilation
      and frequency increased by 15-20% in non-rapid eye movement sleep, and frequency
      increased by 15% in rapid eye movement sleep. There was no effect in wakefulness.
      Chemoreception in the medullary raphe appears to be responsive in sleep. Central
      chemoreceptors at two different locations appear to vary in effectiveness with
      arousal state.

PMID- 11247922
TI  - Effects of smooth muscle activation on axial mechanical properties of excised
      canine bronchi.
AB  - This study tested the hypothesis that airway smooth muscle (ASM) activation
      produces an airway active axial force (AAAF). Bronchi (n = 10) immersed in a
      tissue bath containing 95% O2-5% CO2-equilibrated Krebs solution were subjected
      to passive axial lengthening and shortening at 0-20 cmH2O of transmural pressure.
      ASM was relaxed with isoproterenol and activated with methacholine. Axial tensile
      (epsilonx), transverse compressive (epsilony), and shear strains (epsilonxy) were
      computed from the displacements of four markers placed onto the specimen's
      surface. The AAAF was estimated by subtracting the control axial force (AF)
      values at a given epsilonx from those obtained after methacholine. epsilonx-AF
      relationships were curvilinear, with maximum epsilonx being approached at
      approximately 15 g of AF. The epsilony decreased during bronchial lengthening.
      Cholinergic stimulation produced 1) a decrease of both epsilonx and epsilony at a
      given AF relative to control, indicating ASM shortening, and 2) an AAAF that
      increased with increasing epsilonx and transmural pressure. A portion of the work
      of expanding the lungs is required to lengthen the airways; therefore, an AAAF
      would increase lung elastance and recoil.

PMID- 11247923
TI  - Regional differences in intramyocellular lipids in humans observed by in vivo 1H
      MR spectroscopic imaging.
AB  - Regional differences in the content of intramyocellular lipids (IMCL),
      extramyocellular lipids, and total creatine (TCr) were quantified in soleus (S),
      tibialis posterior (TP), and tibialis anterior (TA) muscles in humans using in
      vivo 1H proton spectroscopic imaging at 4 T. Improved spatial resolution (0.25-ml
      nominal voxel resolution) made it feasible to measure IMCL in S, TP, and TA
      simultaneously in vivo. The most significant regional difference was found in the
      content of IMCL compared with extramyocellular lipids or TCr. The concentrations
      of TCr were found to be 29-32 mmol/kg, with little regional variation. IMCL
      content was measured to be 4.8 +/- 1.6 mmol/kg tissue wt in S, 2.8 +/- 1.3
      mmol/kg tissue wt in TP, and 1.6 +/- 0.9 mmol/kg tissue wt in TA in the order of
      S > TP > TA (P < 0.05). It is likely that these IMCL values are consistent with
      the known fiber types of these muscles, with S having the greatest fraction of
      type I (slow-twitch, oxidative) fibers and TA having a large fraction of type IIb
      (fast-twitch, glycolytic) fibers.

PMID- 11247924
TI  - Interdependence of bronchial circulation and clearance of 99mTc-DTPA from the
      airway surface.
AB  - The extent to which the systemic vasculature is involved in soluble-particle
      uptake in the conducting airways has not been studied extensively. In
      anesthetized, ventilated sheep, 6-10 microl of technetium-99m-labeled
      diethylenetriamine pentaacetic acid (99mTc-DTPA) was delivered through a
      microspray nozzle to a fourth-generation airway. Perfusion of the cannulated
      bronchial artery was varied between control flow (0.6 ml x min(-1) x kg(-1)),
      high flow (1.8 ml x min(-1) x kg(-1)) or no flow (the infusion pump was stopped).
      Airway retention of the radioactive tracer was monitored using gamma camera
      imaging, and venous blood was sampled. During control perfusion, tracer retention
      at the site of deposition at 30 min averaged 20 +/- 6% (n = 7). With no flow,
      retention was significantly elevated to 32 +/- 8% (P = 0.03). In another group of
      sheep (n = 5) with a control retention of 13 +/- 4%, high flow resulted in an
      increase in tracer (25 +/- 4%; P = 0.04). Maximum blood uptake of tracer was
      calculated by estimating circulating blood volume and averaged 16% of total
      activity during control flow. Only during high-flow conditions was 99mTc-DTPA in
      the blood decreased (10%; P = 0.04). Most of the tracer was cleared by
      mucociliary clearance as visualized by imaging. This component was substantially
      decreased during no flow. The results demonstrate that both decreased and
      increased airway perfusion limit removal of soluble tracer applied to the
      conducting airways.

PMID- 11247925
TI  - A method of reconstruction of clinical gas-analyzer signals corrupted by positive
      pressure ventilation.
AB  - The use of sidestream infrared and paramagnetic clinical gas analyzers is
      widespread in anesthesiology and respiratory medicine. For most clinical
      applications, these instruments are entirely satisfactory. However, their ability
      to measure breath-by-breath volumetric gas fluxes, as required for measurement of
      airway dead space, oxygen uptake, and so on, is usually inferior to that of the
      mass spectrometer, and this is thought to be due, in part, to their slower
      response times. We describe how volumetric gas analysis with the Datex Ultima
      analyzer, although reasonably accurate for spontaneous ventilation, gives very
      inaccurate results in conditions of positive-pressure ventilation. We show that
      this problem is a property of the gas sampling system rather than the technique
      of gas analysis itself. We examine the source of this error and describe how
      cyclic changes in airway pressure result in variations in the flow rate of the
      gas within the sampling catheter. This results in the phenomenon of "time
      distortion," and the resultant gas concentration signal becomes a nonlinear time
      series. This corrupted signal cannot be aligned or integrated with the measured
      flow signal. We describe a method to correct for this effect. With the use of
      this method, measurements required for breath-by-breath gas-exchange models can
      be made easily and reliably in the clinical setting.

PMID- 11247926
TI  - c-Fos expression in the central nervous system elicited by phrenic nerve
      stimulation.
AB  - Phrenic nerve afferents (PNa) have been shown to activate neurons in the spinal
      cord, brain stem, and forebrain regions. The c-Fos technique has been widely used
      as a method to identify neuronal regions activated by afferent stimulation. This
      technique was used to identify central neural areas activated by PNa. The right
      phrenic nerve of urethane-anesthetized rats was stimulated in the thorax. The
      spinal cord and brain were sectioned and stained for c-Fos expression. Labeled
      neurons were found in the dorsal horn laminae I and II of the C3-C5 spinal cord
      ipsilateral to the site of PNa stimulation. c-Fos-labeled neurons were found
      bilaterally in the medial subnuclei of the nucleus of the solitary tract, rostral
      ventral respiratory group, and ventrolateral medullary reticular formation. c-Fos
      labeled neurons were found bilaterally in the paraventricular and supraoptic
      hypothalamic nuclei, in the paraventricular thalamic nucleus, and in the central
      nucleus of the amygdala. The presence of c-Fos suggests that these neurons are
      involved in PNa information processing and a component of the central mechanisms
      regulating respiratory function.

PMID- 11247927
TI  - Generation of oxidative stress contributes to the development of pulmonary
      hypertension induced by hypoxia.
AB  - Chronic hypoxia causes pulmonary hypertension and right ventricular hypertrophy
      associated with pulmonary vascular remodeling. Because hypoxia might promote
      generation of oxidative stress in vivo, we hypothesized that oxidative stress may
      play a role in the hypoxia-induced cardiopulmonary changes and examined the
      effect of treatment with the antioxidant N-acetylcysteine (NAC) in rats. NAC
      reduced hypoxia-induced cardiopulmonary alterations at 3 wk of hypoxia. Lung
      phosphatidylcholine hydroperoxide (PCOOH) increased at days 1 and 7 of the
      hypoxic exposure, and NAC attenuated the increase in lung PCOOH. Lung xanthine
      oxidase (XO) activity was elevated from day 1 through day 21, especially during
      the initial 3 days of the hypoxic exposure. The XO inhibitor allopurinol
      significantly inhibited the hypoxia-induced increase in lung PCOOH and pulmonary
      hypertension, and allopurinol treatment only for the initial 3 days also reduced
      the hypoxia-induced right ventricular hypertrophy and pulmonary vascular
      thickening. These results suggest that oxidative stress produced by activated XO
      in the induction phase of hypoxic exposure contributes to the development of
      chronic hypoxic pulmonary hypertension.

PMID- 11247928
TI  - Lactate removal is not enhanced in nonstimulated perfused skeletal muscle after
      endurance training.
AB  - The effects of endurance training (running 40 m/min grade for 60 min, 5 days/wk
      for 8 wk) on skeletal muscle lactate removal was studied in rats by utilizing the
      isolated hindlimb perfusion technique. Hindlimbs were perfused (single-pass) with
      Krebs-Henseleit bicarbonate buffer, fresh bovine erythrocytes (hematocrit
      approximately 30%), 10 mM lactate, and [U-14C]lactate (30,000 dpm/ml). Arterial
      and venous blood samples were collected every 10 min for the duration of the
      experiment to assess lactate uptake. During perfusions, no significant
      differences in skeletal muscle lactate uptake were observed between trained (7.31
      +/- 0.20 micromol/min) and control hindlimbs (6.98 +/- 0.43 micromol/min). In
      support, no significant differences were observed for [14C]lactate uptake in
      trained (22,776 +/- 370 dpm/min) compared with control hindlimbs (21,924 +/-
      1,373 dpm/min). Concomitant with these observations, no significant differences
      were observed between groups for oxygen consumption (4.93 +/- 0.18 vs. 4.92 +/-
      0.13 micromol/min), net skeletal muscle glycogen synthesis (7.1 +/- 0.4 vs. 6.5
      +/- 0.3 micromol x 40 min(-1) x g(-1)), or 14CO2 production (2,203 +/- 185 vs.
      2,098 +/- 155 dpm/min), trained and control, respectively. These findings
      indicate that endurance training does not affect lactate uptake or alter the
      metabolic fate of lactate in quiescent skeletal muscle.

PMID- 11247930
TI  - Overnight responses of the circulating IGF-I system after acute, heavy-resistance
      exercise.
AB  - This study evaluated the individual components of the insulin-like growth factor
      I (IGF-I) system [i.e., total and free IGF-I, insulin-like growth factor binding
      protein (IGFBP)-2 and -3, and the acid-labile subunit (ALS)] in 10 young, healthy
      men (age: 22 +/- 1 yr, height: 177 +/- 2 cm, weight: 79 +/- 3 kg, body fat: 11 +/
      1%) overnight for 13 h after two conditions: a resting control (Con) and an
      acute, heavy-resistance exercise protocol (Ex). The Ex was a high-volume,
      multiset exercise protocol that alternated between 10- and 5-repetition maximum
      sets with 90-s rest periods between sets. The Ex was performed from 1500 to 1700;
      blood was obtained immediately postexercise and sampled throughout the night
      (every 10 min for the first hour and every hour thereafter) until 0600 the next
      morning. For the first hour, significant differences (P < or = 0.05) were only
      observed for IGFBP-3 (Ex: 3,801 > Con: 3,531 ng/ml). For the overnight responses,
      no differences were observed for total or free IGF-I or IGFBP-3, whereas IGFBP-2
      increased (Ex: 561 > Con: 500 ng/ml) and ALS decreased (Ex: 35 < Con: 39
      microg/ml) after exercise. The results from this study suggest that the impact
      that resistance exercise exerts on the circulating IGF-I system is not in the
      alteration of the amount of IGF-I but rather of the manner in which IGF-I is
      partitioned among its family of binding proteins. Thus acute, heavy-resistance
      exercise can lead to alterations in the IGF-I system that can be detected in the
      systemic circulation.

PMID- 11247931
TI  - Endurance training alters outward K+ current characteristics in rat cardiocytes.
AB  - The effect of endurance run training on outward K+ currents with rapidly
      inactivating (I(to)) and sustained or slowly inactivating (I(sus))
      characteristics was examined in left ventricular (LV) cardiocytes isolated from
      sedentary (Sed) and treadmill-trained (Tr) female Sprague-Dawley rats. Isolated
      LV cardiocytes were used in whole cell patch-clamp studies to characterize whole
      cell I(to) and I(sus). Peak I(to) was greatest in cells isolated from the Tr
      group. When I(to) was corrected for cell capacitance to yield a current density,
      most, but not all, of the Sed vs. Tr differences in I(to) magnitude were
      eliminated. Regardless of how I(to) was expressed (e.g., I(to) or I(to) density),
      the time required to achieve a peak value was markedly shortened in the
      cardiocytes isolated from the Tr group. Training elicited a reduction in I(sus)
      density. Action potential characteristics were determined in Sed and Tr
      cardiocytes in primary culture. Training did not affect resting membrane
      potential, whereas peak membrane potential was reduced and time to peak membrane
      potential was prolonged in the Tr group. In addition, time to 50% repolarization
      was significantly increased in cells from the Tr group. Collectively, these data
      indicate that I(to) and I(sus) characteristics are altered by training in
      isolated LV cardiocytes. These alterations in I(to) and I(sus) may be
      responsible, at least in part, for the training-induced alterations in action
      potential configuration in cardiocytes in primary culture.

PMID- 11247929
TI  - Evaluation of laser-Doppler perfusion imaging for measurement of blood flow in
      cortical bone.
AB  - Most techniques currently available to measure blood flow in bone are time
      consuming and require destruction of the tissue, but laser-Doppler technology
      offers a less invasive method. This study assessed the utility of laser-Doppler
      perfusion imaging (LDI) to measure perfusion in cortical bone. Twelve mature New
      Zealand White rabbits were assigned to one of three groups: normal control,
      constriction (norepinephrine), or dilatation (nitroprusside). The left and right
      medial tibiae were consecutively scanned at red (634-nm) and near-infrared (810
      nm) wavelengths to examine the repeatability of LDI output. The pharmacological
      intervention groups were injected with the respective drug, and LDI measurements
      at 810 nm were obtained concurrently with colored microsphere-determined flow in
      all of the groups. LDI effectively quantified blood flow in cortical bone and
      detected physiologically induced changes in perfusion. A significant positive
      correlation was found between microsphere-determined flow and LDI output (r =
      0.6, P < 0.05). Repeatability of consecutive LDI measurements was within 5%. The
      effectiveness of LDI to measure perfusion in bone suggests this method has
      potential for investigating the role of blood flow in bone metabolism and
      remodeling.

PMID- 11247932
TI  - Relationship between fat-to-fat-free mass ratio and decrements in leg strength
      after downhill running.
AB  - The purpose of this study was to determine whether greater body fat mass (FM)
      relative to lean mass would result in more severe muscle damage and greater
      decrements in leg strength after downhill running. The relationship between the
      FM-to-fat-free mass ratio (FM/FFM) and the strength decline resulting from
      downhill running (-11% grade) was investigated in 24 male runners [age 23.4 +/-
      0.7 (SE) yr]. The runners were divided into two groups on the basis of FM/FFM:
      low fat (FM/FFM = 0.100 +/- 0.008, body mass = 68.4 +/- 1.3 kg) and normal fat
      (FM/FFM = 0.233 +/- 0.020, body mass = 76.5 +/- 3.3 kg, P < 0.05). Leg strength
      was reduced less in the low-fat (-0.7 +/- 1.3%) than in the normal-fat
      individuals (-10.3 +/- 1.5%) 48 h after, compared with before, downhill running
      (P < 0.01). Multiple linear regression analysis revealed that the decline in
      strength could be predicted best by FM/FFM (r2 = 0.44, P < 0.05) and FM-to-thigh
      lean tissue cross-sectional area ratio (r2 = 0.53, P < 0.05), with no additional
      variables enhancing the prediction equation. There were no differences in muscle
      glycogen, creatine phosphate, ATP, or total creatine 48 h after, compared with
      before, downhill running; however, the change in muscle glycogen after downhill
      running was associated with a higher FM/FFM (r = -0.56, P < 0.05). These data
      suggest that FM/FFM is a major determinant of losses in muscle strength after
      downhill running.

PMID- 11247933
TI  - Pulmonary perfusion in supine and prone positions: an electron-beam computed
      tomography study.
AB  - Acute respiratory distress syndrome is characterized by alterations in the
      ventilation-perfusion ratio. Present techniques for studying regional pulmonary
      perfusion are difficult to apply in the critically ill. Electron-beam computed
      tomography was used to study the effects of prone positioning on regional
      pulmonary perfusion in six healthy subjects. Contrast-enhanced sections were
      obtained sequentially in the supine, prone, and (original) supine positions at
      full inspiration. Regions of interest were placed along the nondependent to
      dependent axis and relative perfusion calculated. When corrected for the
      redistribution of lung parenchyma, a gravitational gradient of pulmonary
      perfusion existed in both supine and prone positions. The distribution of
      perfusion between the supine or prone positions did not differ, but data analysis
      using smaller regions of interest demonstrated marked heterogeneity of perfusion
      between anatomically adjacent regions of lung. The distribution of lung
      parenchyma was more uniform in the prone position. Gravity was estimated to be
      responsible for 22-34% of perfusion heterogeneity in the supine and 27-41% in the
      prone positions. These data support the hypothesis that factors other than
      gravity may be at least as important in determining the distribution of pulmonary
      perfusion in humans. The influence of nongravitational factors may not be
      detectable if techniques that sample large tissue volumes are employed.

PMID- 11247934
TI  - Behavior of fascicles and tendinous structures of human gastrocnemius during
      vertical jumping.
AB  - Behavior of fascicles and tendinous structures of human gastrocnemius medialis
      (MG) was determined by use of ultrasonography in vivo during jumping. Eight male
      subjects jumped vertically without countermovement (squat jump, SQJ).
      Simultaneously, kinematics, kinetics, and electromyography from lower leg muscles
      were recorded during SQJ. During phase I (-350 to -100 ms before toe-off), muscle
      tendon complex (MTC) length was almost constant. Fascicles, however, shortened by
      26%, and tendinous structures were stretched by 6%, storing elastic energy of 4.9
      J during phase I. During phase II (-100 ms to toe-off), although fascicles
      generated force quasi-isometrically, MTC shortened rapidly by 5.3%, releasing
      prestored elastic energy with a higher peak positive power than that of
      fascicles. Also, the compliance of tendinous structures in vivo was somewhat
      higher than that of external tendon used in the simulation studies. The results
      demonstrate that the compliance of tendinous structures, together with no
      yielding of muscle fibers, allows MTC to effectively generate relatively large
      power at a high joint angular velocity region during the last part of push-off.

PMID- 11247935
TI  - Aged bone displays an increased responsiveness to low-intensity resistance
      exercise.
AB  - The ability of bone to respond to increased loading as a function of age was
      tested by use of three-point bending and histomorphometry. The hindlimbs of male
      Fischer 344 rats of three age groups (young = 4 mo, adult = 12 mo, and old = 22
      mo; n = 10 per age group) were progressively overloaded by training the rats to
      depress a lever high on the side of a cage while wearing a weighted backpack.
      This squatlike movement required full extension of the hindlimbs. Exercised
      (Exer) rats performed 50 repetitions three times per week for 9 wk. Pack weight
      was gradually increased to 65% of body weight. Controls (n = 10 per age group)
      performed the same exercise without additional weight. Neither the mechanical
      properties of the femur nor histomorphometry in the proximal tibia was
      significantly affected in young or adult rats. However, old Exer rats were found
      to have significantly smaller medullary areas and a decreased trabecular spacing
      than their age-matched controls. These results suggest a greater sensitivity to
      increased loading in aged rats.

PMID- 11247936
TI  - Role of ventilation strategy on perfluorochemical evaporation from the lungs.
AB  - To study the effect of ventilation strategy on perfluorochemical (PFC)
      elimination profile (evaporative loss profile; E(L)), 6 ml/kg of perflubron were
      instilled into anesthetized normal rabbits. The strategy was to maintain minute
      ventilation (VE, in ml/min) in three groups: VE(L) (low-range VE, 208 +/- 2),
      VE(M) (midrange VE, 250 +/- 9), and VE(H) (high-range VE, 293 +/- 1) over 4 h. In
      three other groups, respiratory rate (RR, breaths/min) was controlled at 20, 30,
      or 50 with a constant VE and adjusted tidal volume. PFC content in the expired
      gas was measured, and E(L) was calculated. There was a significant VE- and time
      dependent effect on E(L.) Initially, percent PFC saturation and loss rate
      decreased in the VE(H) > VE(M) > VE(L) groups, but by 3 h the lower percent PFC
      saturation resulted in a loss rate such that VE(H) < VE(M) < VE(L) at 4 h. For
      the groups at constant VE, there was a significant time effect on E(L) but no RR
      effect. In conclusion, E(L) profile is dependent on VE with little effect of the
      RR-tidal volume combination. Thus measurement of E(L) and VE should be considered
      for the replacement dosing schemes during partial liquid ventilation.

PMID- 11247938
TI  - Mechanical compression influences intracellular Ca2+ signaling in chondrocytes
      seeded in agarose constructs.
AB  - Ca2+ signaling forms part of a possible mechanotransduction pathway by which
      chondrocytes may alter their metabolism in response to mechanical loading. In
      this study, a well-characterized model system utilizing bovine articular
      chondrocytes embedded in 4% agarose constructs was used to investigate the effect
      of physiological mechanical compressive strain applied after 1 and 3 days in
      culture. The intracellular Ca2+ concentration was measured by use of the
      ratiometric Ca2+ indicator indo 1-AM and confocal microscopy. A positive Ca2+
      response was defined as a percent increase in Ca2+ ratio above a preset
      threshold. A significantly greater percentage of cells exhibited a positive Ca2+
      response in strained constructs compared with unstrained controls at both time
      points. In strained constructs, treatment with either Ga3+ or EGTA significantly
      reduced the number of positive Ca2+ responders compared with untreated controls.
      These results represent an important step in understanding the physiological role
      of intracellular Ca2+ in chondrocytes under mechanical compression.

PMID- 11247937
TI  - MRI study of pharyngeal airway changes during stimulation of the hypoglossal
      nerve branches in rats.
AB  - The medial branch (Med) of the hypoglossal nerve innervates the tongue protrudor
      muscles, whereas the lateral branch (Lat) innervates tongue retractor muscles.
      Our previous finding that pharyngeal airflow increased during either selective
      Med stimulation or whole hypoglossal nerve (WHL) stimulation (coactivation of
      protrudor and retractor muscles) led us to examine how WHL, Med, or Lat
      stimulation affected tongue movements and nasopharyngeal (NP) and oropharyngeal
      (OP) airway volume. Electrical stimulation of either WHL, Med, or Lat nerves was
      performed in anesthetized, tracheotomized rats while magnetic resonance images of
      the NP and OP were acquired (slice thickness 0.5 mm, in-plane resolution 0.25
      mm). NP and OP volume was greater during WHL and Med stimulation vs. no
      stimulation (P < 0.05). Ventral tongue depression (measured in the midsagittal
      images) and OP volume were greater during Med stimulation than during WHL
      stimulation (P < 0.05). Lat stimulation did not alter NP volume (P = 0.39). Our
      finding that either WHL or Med stimulation dilates the NP and OP airways sheds
      new light on the control of pharyngeal airway caliber by extrinsic tongue muscles
      and may lead to new treatments for patients with obstructive sleep apnea.

PMID- 11247939
TI  - Hypnotic manipulation of effort sense during dynamic exercise: cardiovascular
      responses and brain activation.
AB  - The purpose of this investigation was to hypnotically manipulate effort sense
      during dynamic exercise and determine whether cerebral cortical structures
      previously implicated in the central modulation of cardiovascular responses were
      activated. Six healthy volunteers (4 women, 2 men) screened for high
      hypnotizability were studied on 3 separate days during constant-load exercise
      under three hypnotic conditions involving cycling on a 1) perceived level grade,
      2) perceived downhill grade, and 3) perceived uphill grade. Ratings of perceived
      exertion (RPE), heart rate (HR), blood pressure (BP), and regional cerebral blood
      flow (rCBF) distributions for several sites were compared across conditions using
      an analysis of variance. The suggestion of downhill cycling decreased both the
      RPE [from 13 +/- 2 to 11 +/- 2 (SD) units; P < 0.05] and rCBF in the left insular
      cortex and anterior cingulate cortex, but it did not alter exercise HR or BP
      responses. Perceived uphill cycling elicited significant increases in RPE (from
      13 +/- 2 to 14 +/- 1 units), HR (+16 beats/min), mean BP (+7 mmHg), right insular
      activation (+7.7 +/- 4%), and right thalamus activation (+9.2 +/- 5%). There were
      no differences in rCBF for leg sensorimotor regions across conditions. These
      findings show that an increase in effort sense during constant-load exercise can
      activate both insular and thalamic regions and elevate cardiovascular responses
      but that decreases in effort sense do not reduce cardiovascular responses below
      the level required to sustain metabolic needs.

PMID- 11247940
TI  - Lung tissue mechanics and extracellular matrix composition in a murine model of
      silicosis.
AB  - The dynamic mechanical properties of lung tissue and its contents of collagen and
      elastic fibers were studied in strips prepared from mice instilled
      intratracheally with saline (C) or silica [15 (S15) and 30 days (S30) after
      instillation]. Resistance, elastance, and hysteresivity were studied during
      oscillations at different frequencies on S15 and S30. Elastance increased from C
      to silica groups but was similar between S15 and S30. Resistance was augmented
      from C to S15 and S30 and was greater in S30 than in S15 at higher frequencies.
      Hysteresivity was higher in S30 than in C and S15. Silica groups presented a
      greater amount of collagen than did C. Elastic fiber content increased
      progressively along time. This increment was related to the higher amount of
      oxytalan fibers at 15 and 30 days, whereas elaunin and fully developed elastic
      fibers were augmented only at 30 days. Silicosis led not only to pulmonary
      fibrosis but also to fibroelastosis, thus assigning a major role to the elastic
      system in the silicotic lung.

PMID- 11247941
TI  - Exercise-enhanced satellite cell proliferation and new myonuclear accretion in
      rat skeletal muscle.
AB  - The effects of increased functional loading on early cellular regenerative events
      after exercise-induced injury in adult skeletal muscle were examined with the use
      of in vivo labeling of replicating myofiber nuclei and immunocyto- and
      histochemical techniques. Satellite cell proliferation in the soleus (Sol) of
      nonexercised rats (0.4 +/- 0.2% of fibers) was unchanged after an initial bout of
      declined treadmill exercise but was elevated after two (1.0 +/- 0.2%, P < or =
      0.01), but not four or seven, daily bouts of the same task. Myonuclei produced
      over the 7-day period comprised 0.9-1.9% of myonuclei in isolated fibers of Sol,
      tibialis anterior, and vastus intermedius of nonexercised rats. The accretion of
      new myonuclei was enhanced (P < or = 0.05) in Sol and vastus intermedius by the
      initial exercise followed by normal activity (to 3.1-3.4% of myonuclei) and more
      so by continued daily exercise (4.2-5.3%). Observed coincident with a lower
      incidence of histological fiber injury and unchanged fiber diameter and myonuclei
      per millimeter, the greater new myonuclear accretion induced by continued muscle
      loading may contribute to an enhanced fiber repair and regeneration after
      exercise-induced injury.

PMID- 11247942
TI  - Single-breath washouts in a rotating stretcher.
AB  - Vital capacity single-breath washouts using 90% O2-5% He-5% SF6 as a test gas
      mixture were performed with subjects sitting on a stool (upright) or recumbent on
      a stretcher (prone, supine, lateral left, lateral right, with or without rotation
      at end of inhalation). On the basis of the combinations of supine and prone
      maneuvers, gravity-dependent contributions to N2 phase III slope and N2 phase IV
      height in the supine posture were estimated at 18% and 68%, respectively. Whereas
      both He and SF6 slope decreased from supine to prone, the SF6-He slope difference
      actually increased (P = 0.015). N2 phase III slopes, phase IV heights, and
      cardiogenic oscillations were smallest in the prone posture, and we observed
      similarities between the modifications of He and SF6 slopes from upright to prone
      and from upright to short-term microgravity. These results suggest that phase III
      slope is partially due to emptying patterns of small units with different
      ventilation-to-volume ratios, corresponding to acini or groups of acini. Of all
      body postures under study, the prone position most reduces the inhomogeneities of
      ventilation during a vital capacity maneuver at both inter- and intraregional
      levels.

PMID- 11247943
TI  - Effects of vitamin E and alpha-lipoic acid on skeletal muscle contractile
      properties.
AB  - Initial experiments were conducted using an in situ rat tibialis anterior (TA)
      muscle preparation to assess the influence of dietary antioxidants on muscle
      contractile properties. Adult Sprague-Dawley rats were divided into two dietary
      groups: 1) control diet (Con) and 2) supplemented with vitamin E (VE) and alpha
      lipoic acid (alpha-LA) (Antiox). Antiox rats were fed the Con rats' diet (AIN
      93M) with an additional 10,000 IU VE/kg diet and 1.65 g/kg alpha-LA. After an 8
      wk feeding period, no differences existed (P > 0.05) between the two dietary
      groups in maximum specific tension before or after a fatigue protocol or in force
      production during the fatigue protocol. However, in unfatigued muscle, maximal
      twitch tension and tetanic force production at stimulation frequencies < or = 40
      Hz were less (P < 0.05) in Antiox animals compared with Con. To investigate which
      antioxidant was responsible for the depressed force production, a second
      experiment was conducted using an in vitro rat diaphragm preparation. Varying
      concentrations of VE and dihydrolipoic acid, the reduced form of alpha-LA, were
      added either individually or in combination to baths containing diaphragm muscle
      strips. The results from these experiments indicate that high levels of VE
      depress skeletal muscle force production at low stimulation frequencies.

PMID- 11247944
TI  - Intermittent hypoxia increases ventilation and Sa(O2) during hypoxic exercise and
      hypoxic chemosensitivity.
AB  - The purpose of this study was 1) to test the hypothesis that ventilation and
      arterial oxygen saturation (Sa(O2)) during acute hypoxia may increase during
      intermittent hypoxia and remain elevated for a week without hypoxic exposure and
      2) to clarify whether the changes in ventilation and Sa(O2) during hypoxic
      exercise are correlated with the change in hypoxic chemosensitivity. Six subjects
      were exposed to a simulated altitude of 4,500 m altitude for 7 days (1 h/day).
      Oxygen uptake (VO2), expired minute ventilation (VE), and Sa(O2) were measured
      during maximal and submaximal exercise at 432 Torr before (Pre), after
      intermittent hypoxia (Post), and again after a week at sea level (De). Hypoxic
      ventilatory response (HVR) was also determined. At both Post and De, significant
      increases from Pre were found in HVR at rest and in ventilatory equivalent for O2
      (VE/VO2) and Sa(O2) during submaximal exercise. There were significant
      correlations among the changes in HVR at rest and in VE/VO2 and Sa(O2) during
      hypoxic exercise during intermittent hypoxia. We conclude that 1 wk of daily
      exposure to 1 h of hypoxia significantly improved oxygenation in exercise during
      subsequent acute hypoxic exposures up to 1 wk after the conditioning, presumably
      caused by the enhanced hypoxic ventilatory chemosensitivity.

PMID- 11247945
TI  - Respiratory dynamics during laughter.
AB  - Lung and chest wall mechanics were studied during fits of laughter in 11 normal
      subjects. Laughing was naturally induced by showing clips of the funniest scenes
      from a movie by Roberto Benigni. Chest wall volume was measured by using a three
      dimensional optoelectronic plethysmography and was partitioned into upper thorax,
      lower thorax, and abdominal compartments. Esophageal (Pes) and gastric (Pga)
      pressures were measured in seven subjects. All fits of laughter were
      characterized by a sudden occurrence of repetitive expiratory efforts at an
      average frequency of 4.6 +/- 1.1 Hz, which led to a final drop in functional
      residual capacity (FRC) by 1.55 +/- 0.40 liter (P < 0.001). All compartments
      similarly contributed to the decrease of lung volumes. The average duration of
      the fits of laughter was 3.7 +/- 2.2 s. Most of the events were associated with
      sudden increase in Pes well beyond the critical pressure necessary to generate
      maximum expiratory flow at a given lung volume. Pga increased more than Pes at
      the end of the expiratory efforts by an average of 27 +/- 7 cmH2O.
      Transdiaphragmatic pressure (Pdi) at FRC and at 10% and 20% control forced vital
      capacity below FRC was significantly higher than Pdi at the same absolute lung
      volumes during a relaxed maneuver at rest (P < 0.001). We conclude that fits of
      laughter consistently lead to sudden and substantial decrease in lung volume in
      all respiratory compartments and remarkable dynamic compression of the airways.
      Further mechanical stress would have applied to all the organs located in the
      thoracic cavity if the diaphragm had not actively prevented part of the increase
      in abdominal pressure from being transmitted to the chest wall cavity.

PMID- 11247946
TI  - Scoring of surface parameters of physiological relevance to surfactant therapy in
      respiratory distress syndrome.
AB  - The Wilhelmy balance was used for in vitro testing of surface parameters of
      surfactants used for respiratory distress syndrome therapy. Two commercial
      protein-free surfactants, ALEC and Exosurf, were compared with pure forms of the
      three main phospholipids in natural surfactants, dipalmitoyl phosphatidylcholine
      (PC), phosphatidylglycerol (PG), and phosphatidylethanolamine (PE), and their
      binary mixtures, PC with PE and PG each in the ratio 2:3. Surface excess films
      (15 A2/molecule) were compressed at 1.2 cycles/min past collapse to a compression
      ratio of 4:1. The maximum surface pressure, spreading time, compressibility,
      respreading ratio, recruitment index, and hysteresis area were compared. A
      consolidated list of criteria for selection of suitable surfactants was compiled
      from the literature. A relative scoring system was devised for comparison based
      on these criteria. PC/PG (2:3) performed the best as it fulfilled all the
      criteria and obtained the highest relative score. Exosurf also performed well,
      except on the respreading criterion. ALEC and PC/PE were equivalent in their
      performance and performed well, except on two criteria: hysteresis area and
      recruitment index. Thus the scoring system proposed here proved valuable to rate
      the overall efficacy as well as relative merits of surfactant formulations.

PMID- 11247948
TI  - Baroreceptor modulation of active cutaneous vasodilation during dynamic exercise
      in humans.
AB  - The hypothesis that baroreceptor unloading during dynamic limits cutaneous
      vasodilation by withdrawal of active vasodilator activity was tested in seven
      human subjects. Increases in forearm skin blood flow (laser-Doppler velocimetry)
      at skin sites with (control) and without alpha-adrenergic vasoconstrictor
      activity (vasodilator only) and in arterial blood pressure (noninvasive) were
      measured and used to calculate cutaneous vascular conductance (CVC). Subjects
      performed two similar dynamic exercise (119 +/- 8 W) protocols with and without
      baroreceptor unloading induced by application of -40 mmHg lower body negative
      pressure (LBNP). The LBNP condition was reversed (i.e., either removed or
      applied) after 15 min while exercise continued for an additional 15 min. During
      exercise without LBNP, the increase in body core temperature (esophageal
      temperature) required to elicit active cutaneous vasodilation averaged 0.25 +/-
      0.08 and 0.31 +/- 0.10 degrees C (SE) at control and vasodilator-only skin sites,
      respectively, and increased to 0.44 +/- 0.10 and 0.50 +/- 0.10 degrees C (P <
      0.05 compared with without LBNP) during exercise with LBNP. During exercise
      baroreceptor unloading delayed the onset of cutaneous vasodilation and limited
      peak CVC at vasodilator-only skin sites. These data support the hypothesis that
      during exercise baroreceptor unloading modulates active cutaneous vasodilation.

PMID- 11247949
TI  - Role of nitric oxide during hyperventilation-induced bronchoconstriction in the
      guinea pig.
AB  - Airway function is largely preserved during exercise or isocapnic
      hyperventilation in humans and guinea pigs despite likely changes in airway
      milieu during hyperpnea. It is only on cessation of a hyperpneic challenge that
      airway function deteriorates significantly. We tested the hypothesis that nitric
      oxide, a known bronchodilator that is produced in the lungs and bronchi, might be
      responsible for the relative bronchodilation observed during hyperventilation
      (HV) in guinea pigs. Three groups of anesthetized guinea pigs were given saline
      and three groups given 50 mg/kg N(G)-monomethyl-L-arginine (L-NMMA), a potent
      nitric oxide synthase inhibitor. Three isocapnic ventilation groups included
      normal ventilation [40 breaths/min, 6 ml/kg tidal volume (VT)], increased
      respiratory rate only (150 breaths/min, 6 ml/kg VT), and increased respiratory
      rate and increased volume (100 breaths/min, 8 ml/kg VT). L-NMMA reduced expired
      nitric oxide in all groups. Expired nitric oxide was slightly but significantly
      increased by HV in the saline groups. However, inhibition of nitric oxide
      production had no significant effect on rate of rise of respiratory system
      resistance (Rrs) during HV or on the larger rise in Rrs seen 6 min after HV. We
      conclude that nitric oxide synthase inhibition has no effect on changes in Rrs,
      either during or after HV in guinea pigs.

PMID- 11247950
TI  - Static and dynamic operating characteristics of a pericardial balloon.
AB  - Previously, we developed a balloon transducer to measure the constraint of the
      pericardium (i.e., pericardial pressure) on the surface of the heart. It was
      validated physiologically in that it was shown to measure a pressure equal to the
      difference between the left ventricular end-diastolic pressure measured before
      and after pericardiectomy at the same left ventricular volume. To define its
      static operating characteristics, we loaded the balloon nonuniformly with weights
      that covered fractions of the balloon surface and found that the balloon
      accurately recorded the average stress if the stress was applied over at least
      23% of its surface. To test its performance when curved, we placed it in large
      and small cylinders (minimum diameter 31 mm) and found that the balloon
      accurately recorded the stress. To define its dynamic operating characteristics,
      we applied sinusoidal stresses and found that its frequency response was limited
      only by that of the connecting catheter. When better dynamic response is
      required, we introduce a micromanometer-tipped catheter to obtain a unity-gain
      frequency response that is flat to 200 Hz.

PMID- 11247947
TI  - Cardiac and respiratory activity at arousal from sleep under controlled
      ventilation conditions.
AB  - Arousal from sleep is associated with elevated cardiac and respiratory activity.
      It is unclear whether this occurs because of homeostatic mechanisms or a reflex
      activation response associated with arousal. Cardiorespiratory activity was
      measured during spontaneous arousals from sleep in subjects breathing passively
      on a ventilator. Under such conditions, homeostatic mechanisms are eliminated.
      Ventilation, end-tidal PCO2, mask pressure, diaphragmatic electromyograph, heart
      rate, and blood pressure were measured in four normal subjects under two
      conditions: assisted ventilation and a normal ventilation control condition. In
      the control condition, there was a normal, sleep-related fall in ventilation and
      rise in end-tidal PCO2. Subsequently, at an arousal, there was an increase in
      respiratory and cardiac activity. In the ventilator condition, a vigorous
      cardiorespiratory response to a spontaneous arousal from sleep remained. These
      results indicate that sleep-related respiratory stimuli are not necessary for the
      occurrence of elevated cardiorespiratory activity at an arousal from sleep and
      are consistent with the hypothesis that such activity is at least in part due to
      a reflex activation response.

PMID- 11247951
TI  - Contribution of amiloride-insensitive pathways to alveolar fluid clearance in
      adult rats.
AB  - The contributions of amiloride-sensitive and -insensitive fractions of alveolar
      fluid clearance in adult ventilated rats were studied under control conditions
      and after beta-adrenergic stimulation. Rats were instilled with a 5% albumin
      solution containing terbutaline (10(-4) M) or dibutyryl-cGMP (DBcGMP; 10(-4) M)
      with or without the cyclic nucleotide-gated cation channel inhibitor l-cis
      diltiazem (10(-3) M) and/or amiloride (10(-3) M). Alveolar fluid clearance over 1
      h was 18 +/- 2% in controls. In controls, amiloride inhibited 46 +/- 15% of
      alveolar fluid clearance, whereas l-cis-diltiazem had no inhibitory effect.
      Terbutaline and DBcGMP stimulated alveolar fluid clearance by 85 +/- 3 and 36 +/-
      5%, respectively. Amiloride and l-cis-diltiazem inhibited nearly equal fractions
      of terbutaline-stimulated alveolar fluid clearance when given alone. Amiloride
      and l-cis-diltiazem given together inhibited a significantly larger fraction of
      alveolar fluid clearance in terbutaline-stimulated rats and in DBcGMP-stimulated
      rats. Based on these data, terbutaline stimulation recruited both amiloride
      sensitive and l-cis-diltiazem-sensitive pathways. In contrast, DBcGMP mainly
      recruited l-cis-diltiazem-sensitive pathways. Therefore, the amiloride
      insensitive fraction of Na+-driven alveolar fluid clearance may be partly
      mediated through cyclic nucleotide-gated cation channels and activated by an
      increase in intracellular cGMP.

PMID- 11247952
TI  - Effects of strength training on muscle power and serum hormones in middle-aged
      and older men.
AB  - Effects of 16-wk strength training on maximal strength and power performance of
      the arm and leg muscles and serum concentrations [testosterone (T), free
      testosterone (FT), and cortisol] were examined in 11 middle-aged (M46; 46 +/- 2
      yr) and 11 older men (M64; 64 +/- 2 yr). During the 16-wk training, the relative
      increases in maximal strength and muscle power output of the arm and leg muscles
      were significant in both groups (P < 0.05-0.001), with no significant differences
      between the two groups. The absolute increases were higher (P < 0.01-0.05) in M46
      than in M64 mainly during the last 8 wk of training. No significant changes were
      observed for serum T and FT concentrations. Analysis of covariance showed that,
      during the 16-wk training period, serum FT concentrations tended to decrease in
      M64 and increase in M46 (P < 0.05). However, significant correlations between the
      mean level of individual serum T and FT concentrations and the individual changes
      in maximal strength were observed in a combined group during the 16-wk training
      (r = 0.49 and 0.5, respectively; P < 0.05). These data indicate that a prolonged
      total strength-training program would lead to large gains in maximal strength and
      power load characteristics of the upper and lower extremity muscles, but the
      pattern of maximal and power development seemed to differ between the upper and
      lower extremities in both groups, possibly limited in magnitude because of
      neuromuscular and/or age-related endocrine impairments.

PMID- 11247953
TI  - Endotoxemia increases relative perfusion to dorsal-caudal lung regions.
AB  - Changes in the spatial distribution of perfusion during acute lung injury and
      their impact on gas exchange are poorly understood. We tested whether endotoxemia
      caused topographical differences in perfusion and whether these differences
      caused meaningful changes in regional ventilation-to-perfusion ratios and gas
      exchange. Regional ventilation and perfusion were measured in anesthetized,
      mechanically ventilated pigs in the prone position before and during endotoxemia
      with the use of aerosolized and intravenous fluorescent microspheres. On average,
      relative perfusion halved in ventral and cranial lung regions, doubled in caudal
      lung regions, and increased 1.5-fold in dorsal lung regions during endotoxemia.
      In contrast, there were no topographical differences in perfusion before
      endotoxemia and no topographical differences in ventilation at any time point.
      Consequently, endotoxemia increased regional ventilation-to-perfusion ratios in
      the caudal-to-cranial and dorsal-to-ventral directions, resulting in end
      capillary PO2 values that were significantly lower in dorsal-caudal than ventral
      cranial regions. We conclude that there are topographical differences in the
      pulmonary vascular response to endotoxin that may have important consequences for
      gas exchange in acute lung injury.

PMID- 11247954
TI  - Hypoxia augments apnea-induced peripheral vasoconstriction in humans.
AB  - Obstructive apnea and voluntary breath holding are associated with transient
      increases in muscle sympathetic nerve activity (MSNA) and arterial pressure. The
      contribution of changes in blood flow relative to the contribution of changes in
      vascular resistance to the apnea-induced transient rise in arterial pressure is
      unclear. We measured heart rate, mean arterial blood pressure (MAP), MSNA
      (peroneal microneurography), and femoral artery blood velocity (V(FA), Doppler)
      in humans during voluntary end-expiratory apnea while they were exposed to room
      air, hypoxia (10.5% inspiratory fraction of O2), and hyperoxia (100% inspiratory
      fraction of O2). Changes from baseline of leg blood flow (Q) and vascular
      resistance (R) were estimated from the following relationships: Q proportional to
      V(FA), corrected for the heart rate, and R proportional to MAP/Q. During apnea,
      MSNA rose; this rise in MSNA was followed by a rise in MAP, which peaked a few
      seconds after resumption of breathing. Responses of MSNA and MAP to apnea were
      greatest during hypoxia and smallest during hyperoxia (P < 0.05 for both compared
      with room air breathing). Similarly, apnea was associated with a decrease in Q
      and an increase in R. The decrease in Q was greatest during hypoxia and smallest
      during hyperoxia (-25 +/- 3 vs. -6 +/- 4%, P < 0.05), and the increase in R was
      the greatest during hypoxia and the least during hyperoxia (60 +/- 8 vs. 21 +/-
      6%, P < 0.05). Thus voluntary apnea is associated with vasoconstriction, which is
      in part mediated by the sympathetic nervous system. Because apnea-induced
      vasoconstriction is most intense during hypoxia and attenuated during hyperoxia,
      it appears to depend at least in part on stimulation of arterial chemoreceptors.

PMID- 11247955
TI  - Muscularity and the density of the fat-free mass in athletes.
AB  - The purpose of this study was to use estimates of body composition from a four
      component model to determine whether the density of the fat-free mass (D(FFM)) is
      affected by muscularity or musculoskeletal development in a heterogenous group of
      athletes and nonathletes. Measures of body density by hydrostatic weighing, body
      water by deuterium dilution, bone mineral by whole body dual-energy X-ray
      absorptiometry (DXA), total body skeletal muscle estimated from DXA, and
      musculoskeletal development as measured by the mesomorphy rating from the Heath
      Carter anthropometric somatotype were obtained in 111 collegiate athletes (67 men
      and 44 women) and 61 nonathletes (24 men and 37 women). In the entire group,
      D(FFM) varied from 1.075 to 1.127 g/cm3 and was strongly related to the water and
      protein fractions of the fat-free mass (FFM; r = -0.96 and 0.89) and moderately
      related to the mineral fraction of the FFM (r = 0.65). Skeletal muscle (%FFM)
      varied from 40 to 68%, and mesomorphy varied from 1.6 to 9.6, but neither was
      significantly related to D(FFM) (r = 0.11 and -0.14) or to the difference between
      percent fat estimated from the four-component model and from densitometry (r =
      0.09 and -0.16). We conclude that, in a heterogeneous group of young adult
      athletes and nonathletes, D(FFM) and the accuracy of estimates of body
      composition from body density using the Siri equation are not related to
      muscularity or musculoskeletal development. Athletes in selected sports may have
      systematic deviations in D(FFM) from the value of 1.1 g/cm3 assumed in the Siri
      equation, resulting in group mean errors in estimation of percent fat from
      densitometry of 2-5% body mass, but the cause of these deviations is complex and
      not simply a reflection of differences in muscularity or musculoskeletal
      development.

PMID- 11247957
TI  - Ventilatory effects of impaired glial function in a brain stem chemoreceptor
      region in the conscious rat.
AB  - Glia are thought to regulate ion homeostasis, including extracellular pH;
      however, their role in modulating central CO2 chemosensitivity is unclear. Using
      a push-pull cannula in chronically instrumented and conscious rats, we
      administered a glial toxin, fluorocitrate (FC; 1 mM) into the retrotrapezoid
      nucleus (RTN), a putative chemosensitive site, during normocapnia and
      hypercapnia. FC exposure significantly increased expired minute ventilation (VE)
      to a value 38% above the control level during normocapnia. During hypercapnia, FC
      also significantly increased both breathing frequency and expired VE. During FC
      administration, maximal ventilation was achieved at approximately 4% CO2,
      compared with 8-10% CO2 during control hypercapnic trials. RTN perfusion of
      control solutions had little effect on any ventilatory measures (VE, tidal
      volume, or breathing frequency) during normocapnic or hypercapnic conditions. We
      conclude that unilateral impairment of glial function in the RTN of the conscious
      rat results in stimulation of respiratory output.

PMID- 11247956
TI  - Chronic hypoxia attenuates resting and exercise-induced VEGF, flt-1, and flk-1
      mRNA levels in skeletal muscle.
AB  - Vascular endothelial growth factor (VEGF) is a hypoxia-inducible angiogenic
      mitogen. However, chronic hypoxia is generally not found to increase mammalian
      skeletal muscle capillarity. We sought to determine the effect of chronic hypoxia
      (8 wk, inspired O2 fraction = 0.12) on skeletal muscle gene expression of VEGF,
      its receptors (flt-1 and flk-1), basic fibroblast growth factor, and transforming
      growth factor-beta1. Wistar rats were exposed to chronic hypoxia (n = 12) or room
      air (n = 12). After the exposure period, six animals from each group were
      subjected to a single 1-h treadmill exercise bout (18 m/min on a 10 degrees
      incline) in room air while the remaining six animals served as rest controls.
      Morphological analysis revealed that chronic hypoxia did not increase skeletal
      muscle capillarity. Northern blot analyses showed that chronic hypoxia decreased
      resting VEGF, flt-1, and flk-1 mRNA by 23, 68, and 42%, respectively (P < 0.05).
      The VEGF mRNA response to exercise was also decreased (4.1- and 2.7-fold increase
      in room air and chronic hypoxia, respectively, P < 0.05). In contrast, neither
      transforming growth factor-beta1 nor basic fibroblast growth factor mRNA was
      significantly altered by chronic hypoxia. In conclusion, prolonged exposure to
      hypoxia attenuated gene expression of VEGF and its receptors flt-1 and flk-1 in
      rat gastrocnemius muscle. These findings may provide an explanation for the lack
      of mammalian skeletal muscle angiogenesis that is observed after chronic hypoxia.

PMID- 11247958
TI  - Effect of load on preferred speed and cost of transport.
AB  - Horses have a tendency to utilize a relatively narrow set of speeds near the
      middle of a much broader range they are capable of using within a particular
      gait, i.e., a preferred speed. Possible explanations for this behavior include
      minimizing musculoskeletal stresses and maximizing metabolic economy. If
      metabolic economy (cost of transport, CT) and preferred speeds are linked, then
      shifts in CT should produce shifts in preferred speed. To test this hypothesis,
      preferred speed was measured in trotting horses (n = 7) unloaded on the level and
      loaded with 19% of their body weight on the level. The preferred speed on the
      level was 3.33 +/- 0.09 (SE) m/s, and this decreased to 3.13 +/- 0.11 m/s when
      loaded. In both conditions (no load and load), the rate of O2 consumption (n = 3)
      was a curvilinear function of speed that produced a minimum CT (i.e., speed at
      which trotting is most economical). When unloaded, the speed at which CT was
      minimum was very near the preferred speed. With a load, CT decreased and the
      minimum was also near the preferred speed of horses while carrying a load.

PMID- 11247959
TI  - Effects of spaceflight on human calf hemodynamics.
AB  - Chronic microgravity may modify adaptations of the leg circulation to
      gravitational pressures. We measured resting calf compliance and blood flow with
      venous occlusion plethysmography, and arterial blood pressure with
      sphygmomanometry, in seven subjects before, during, and after spaceflight. Calf
      vascular resistance equaled mean arterial pressure divided by calf flow.
      Compliance equaled the slope of the calf volume change and venous occlusion
      pressure relationship for thigh cuff pressures of 20, 40, 60, and 80 mmHg held
      for 1, 2, 3, and 4 min, respectively, with 1-min breaks between occlusions. Calf
      blood flow decreased 41% in microgravity (to 1.15 +/- 0.16 ml x 100 ml(-1) x min(
      1)) relative to 1-G supine conditions (1.94 +/- 0.19 ml x 100 ml(-1) x min(-1), P
      = 0.01), and arterial pressure tended to increase (P = 0.05), such that calf
      vascular resistance doubled in microgravity (preflight: 43 +/- 4 units; in
      flight: 83 +/- 13 units; P < 0.001) yet returned to preflight levels after
      flight. Calf compliance remained unchanged in microgravity but tended to increase
      during the first week postflight (P > 0.2). Calf vasoconstriction in microgravity
      qualitatively agrees with the "upright set-point" hypothesis: the circulation
      seeks conditions approximating upright posture on Earth. No calf hemodynamic
      result exhibited obvious mechanistic implications for postflight orthostatic
      intolerance.

PMID- 11247960
TI  - Inconsistent link between low-frequency oscillations: R-R interval responses to
      augmented Mayer waves.
AB  - Low-frequency oscillations in arterial blood pressure (Mayer waves) and R-R
      interval are thought to be linked through the arterial baroreflex. To delve into
      this relationship, we applied low (10 mmHg) and moderate (30 mmHg) lower body
      negative pressure (LBNP) in 10-s cycles to 18 healthy young male subjects. They
      showed no change in average blood pressure with this oscillatory stimulus but did
      show a significant decrease in R-R interval (P < 0.05) during both levels of
      LBNP. In addition, we succeeded in augmenting low-frequency blood pressure
      oscillations in a graded response to oscillatory LBNP level (P < 0.05) while
      significantly increasing low-frequency R-R interval oscillations (P < 0.05).
      However, cross-spectral coherence between these increased oscillations was highly
      variable across individuals and stimulus level. Although nearly all subjects
      showed significant coherence during basal conditions (n = 17), only seven
      subjects maintained significant coherence during both levels of LBNP. These
      results suggest that a complex interaction of regulatory mechanisms determines
      the link between low-frequency oscillations and the responses to even low levels
      of LBNP.

PMID- 11247961
TI  - Effects of SNP, ouabain, and amiloride on electrical potential profile of
      isolated sheep pleura.
AB  - The fluid and solute transport properties of pleural tissue were studied by using
      specimens of intact visceral and parietal pleura from adult sheep lungs. The
      samples were transferred to the laboratory in a Krebs-Ringer solution at 4
      degrees C within 1 h from the death of the animal. The pleura was then mounted as
      a planar sheet in a Ussing-type chamber. The results that are presented in this
      study are the means of six different experiments. The spontaneous potential
      difference and the inhibitory effects of sodium nitroprusside (SNP), ouabain, and
      amiloride on transepithelial electrical resistance (R(TE)) were measured. The
      spontaneous potential difference across parietal pleura was 0.5 +/- 0.1 mV,
      whereas that across visceral pleura was 0.4 +/- 0.1 mV. R(TE) of both pleura was
      very low: 22.02 +/- 4.1 Omega. cm2 for visceral pleura and 22.02 +/- 3.5 Omega.
      cm2 for parietal pleura. There was an increase in the R(TE) when SNP was added to
      the serosal bathing solution of parietal pleura and to the serosal or mucosal
      bathing solution in visceral pleura. The same was observed when ouabain was added
      to the mucosal surface of visceral pleura and to either the mucosal or serosal
      surface of parietal pleura. Furthermore, there was an increase in R(TE) when
      amiloride was added to the serosal bathing solution of parietal pleura.
      Consequently, the sheep pleura appears to play a role in the fluid and solute
      transport between the pleural capillaries and the pleural space. There results
      suggest that there is a Na+ and K+ transport across both the visceral and
      parietal pleura.

PMID- 11247962
TI  - Central GABAergic mechanisms are involved in apnea induced by SLN stimulation in
      piglets.
AB  - Stimulation of the superior laryngeal nerve (SLN) results in apnea in animals of
      different species, the mechanism of which is not known. We studied the effect of
      the GABA(A) receptor blocker bicuculline, given intravenously and
      intracisternally, on apnea induced by SLN stimulation. Eighteen 5- to 10-day-old
      piglets were studied: bicuculline was administered intravenously to nine animals
      and intracisternally to nine animals. The animals were anesthetized and then
      decerebrated, vagotomized, ventilated, and paralyzed. The phrenic nerve responses
      to four levels of electrical SLN stimulation were measured before and after
      bicuculline. SLN stimulation caused a significant decrease in phrenic nerve
      amplitude, phrenic nerve frequency, minute phrenic activity, and inspiratory time
      (P < 0.01) that was proportional to the level of electrical stimulation.
      Increased levels of stimulation were more likely to induce apnea during
      stimulation that often persisted beyond cessation of the stimulus. Bicuculline,
      administered intravenously or intracisternally, decreased the SLN stimulation
      induced decrease in phrenic nerve amplitude, minute phrenic activity, and phrenic
      nerve frequency (P < 0.05). Bicuculline also reduced SLN-induced apnea and
      duration of poststimulation apnea (P < 0.05). We conclude that centrally mediated
      GABAergic pathways are involved in laryngeal stimulation-induced apnea.

PMID- 11247963
TI  - Effects of morphine and naloxone on fetal heart rate and movement in the pig.
AB  - To test the hypothesis that an increasing opioid tonus is involved in decreases
      in fetal heart rate (FHR) and movement (FM) during late gestation, we studied the
      effects of intravenous bolus injections of morphine (1 mg) and naloxone (1 mg) on
      FHR and FM in the fetal pig. Twenty-one fetuses (1 per sow) were catheterized at
      90-104 days of gestation (median 100 days). Recordings of FHR (electrocardiograph
      or Doppler-derived signals) and FM (ultrasonography) were made from 15 min before
      to 45 min after treatment. Morphine administration significantly decreased FHR,
      but it increased FHR variation and forelimb movements (LM). LM were clustered,
      and this stereotyped behavior has never before been observed in any mammalian
      fetus. Naloxone administration increased gross body movements and FHR without
      significant changes in FHR variation. It is concluded that FHR and motility are
      under opioidergic control in the pig fetus. Both morphine and naloxone induce
      hypermotility, suggesting that naloxone does not act as a pure opioid antagonist
      in the fetal pig.

PMID- 11247964
TI  - Airway branching morphology of mature and immature rabbit lungs.
AB  - The scheme of Horsfield et al. for describing the pulmonary airway tree (J Appl
      Physiol 52: 21-26, 1982) catalogs each airway according to its order and the
      difference in order of its two daughters (denoted Delta). Although this scheme
      captures the natural asymmetry in the airway tree, it is still deterministic,
      because it assumes that all airways of a given order are the same; yet such
      variability is extremely important in determining the overall behavior of the
      lungs. We therefore analyzed complete lung lobes from three mature and two
      immature rabbits and determined the Horsfield order and Delta of every airway
      down to the terminal bronchioles. We also measured the diameter of each airway.
      This allowed us to determine the average structure of the rabbit airway tree, the
      variation about this average, and also how the structures of mature and immature
      airway trees compare. We found some variation in branching asymmetry and airway
      diameter at a given order between animals but no evidence of systematic
      differences in structure between mature and immature lungs. We found evidence of
      a difference in the branching structure of the peripheral vs. the central part of
      the airway tree (the break point being around order 20). We also determined the
      nature of the variation in Delta and diameter as a function of order, which
      should be valuable for the development of computer models seeking to encapsulate
      the naturally occurring regional variation in airway geometry in the normal
      rabbit lung.

PMID- 11247965
TI  - Invited review: Physiological and pathophysiological responses to intermittent
      hypoxia.
AB  - This mini-review summarizes the physiological adaptations to and
      pathophysiological consequences of intermittent hypoxia with special emphasis
      given to the pathophysiology associated with obstructive sleep apnea.
      Intermittent hypoxia is an effective stimulus for evoking the respiratory,
      cardiovascular, and metabolic adaptations normally associated with continuous
      chronic hypoxia. These adaptations are thought by some to be beneficial in that
      they may provide protection against disease as well as improve exercise
      performance in athletes. The long-term consequences of chronic intermittent
      hypoxia may have detrimental effects, including hypertension, cerebral and
      coronary vascular problems, developmental and neurocognitive deficits, and
      neurodegeneration due to the cumulative effects of persistent bouts of hypoxia.
      Emphasis is placed on reviewing the available data on intermittent hypoxia,
      making extensions from applicable information from acute and chronic hypoxia
      studies, and pointing out major gaps in information linking the genomic and
      cellular responses to intermittent hypoxia with physiological or
      pathophysiological responses.

PMID- 11247966
TI  - Invited review: Physiological consequences of intermittent hypoxia: systemic
      blood pressure.
AB  - One of the major manifestations of obstructive sleep apnea is profound and
      repeated hypoxia during sleep. Acute hypoxia leads to stimulation of the
      peripheral chemoreceptors, which in turn increases sympathetic outflow, acutely
      increasing blood pressure. The chronic effect of these repeated episodic or
      intermittent periods of hypoxia in humans is difficult to study because chronic
      cardiovascular changes may take many years to manifest. Rodents have been a
      tremendous source of information in short- and long-term studies of hypertension
      and other cardiovascular diseases. Recurrent short cycles of normoxia-hypoxia,
      when administered to rats for 35 days, allows examination of the chronic
      cardiovascular response to intermittent hypoxia patterned after the episodic
      desaturation seen in humans with sleep apnea. The result of this type of
      intermittent hypoxia in rats is a 10- to 14-mmHg increase in resting
      (unstimulated) mean blood pressure that lasts for several weeks after cessation
      of the daily cyclic hypoxia. Carotid body denervation, sympathetic nerve
      ablation, renal sympathectomy, adrenal medullectomy, and angiotensin II receptor
      blockade block the blood pressure increase. It appears that adrenergic and renin
      angiotensin system overactivity contributes to the early chronic elevated blood
      pressure in rat intermittent hypoxia and perhaps to human hypertension associated
      with obstructive sleep apnea.

PMID- 11247968
TI  - Selected contribution: chemoreflex responses to CO2 before and after an 8-h
      exposure to hypoxia in humans.
AB  - The ventilatory sensitivity to CO2, in hyperoxia, is increased after an 8-h
      exposure to hypoxia. The purpose of the present study was to determine whether
      this increase arises through an increase in peripheral or central
      chemosensitivity. Ten healthy volunteers each underwent 8-h exposures to 1)
      isocapnic hypoxia, with end-tidal PO2 (PET(O2)) = 55 Torr and end-tidal PCO2
      (PET(CO2)) = eucapnia; 2) poikilocapnic hypoxia, with PET(O2) = 55 Torr and
      PET(CO2) = uncontrolled; and 3) air-breathing control. The ventilatory response
      to CO2 was measured before and after each exposure with the use of a
      multifrequency binary sequence with two levels of PET(CO2): 1.5 and 10 Torr above
      the normal resting value. PET(O2) was held at 250 Torr. The peripheral (Gp) and
      the central (Gc) sensitivities were calculated by fitting the ventilatory data to
      a two-compartment model. There were increases in combined Gp + Gc (26%, P <
      0.05), Gp (33%, P < 0.01), and Gc (23%, P = not significant) after exposure to
      hypoxia. There were no significant differences between isocapnic and
      poikilocapnic hypoxia. We conclude that sustained hypoxia induces a significant
      increase in chemosensitivity to CO2 within the peripheral chemoreflex.

PMID- 11247969
TI  - Selected contribution: variation in acute hypoxic ventilatory response is linked
      to mouse chromosome 9.
AB  - Genetic determinants confer variation among inbred mouse strains with respect to
      the magnitude and pattern of breathing during acute hypoxic challenge.
      Specifically, inheritance patterns derived from C3H/HeJ (C3) and C57BL/6J (B6)
      parental strains suggest that differences in hypoxic ventilatory response (HVR)
      are controlled by as few as two genes. The present study demonstrates that at
      least one genetic determinant is located on mouse chromosome 9. This genotype
      phenotype association was established by phenotyping 52 B6C3F2 (F2) offspring for
      HVR characteristics. A genome-wide screen was performed using microsatellite DNA
      markers (n = 176) polymorphic between C3 and B6 mice. By computing log-likelihood
      values (LOD scores), linkage analysis compared marker genotypes with minute
      ventilation (&Vdot;E), tidal volume (VT), and mean inspiratory flow (VT/TI, where
      TI is inspiratory time) during acute hypoxic challenge (inspired O2 fraction =
      0.10, inspired CO2 fraction = 0.03 in N2). A putative quantitative trait locus
      (QTL) positioned in the vicinity of D9Mit207 was significantly associated with
      hypoxic VE (LOD = 4.5), VT (LOD = 4.0), and VT/TI (LOD = 5.1). For each of the
      three HVR characteristics, the putative QTL explained more than 30% of the
      phenotypic variation among F(2) offspring. In conclusion, this genetic model of
      differential HVR characteristics demonstrates that a locus approximately 33
      centimorgans from the centromere on mouse chromosome 9 confers a substantial
      proportion of the variance in VE, VT, and VT/TI during acute hypoxic challenge.

PMID- 11247970
TI  - Selected contribution: role of spleen emptying in prolonging apneas in humans.
AB  - This study addressed the interaction between short-term adaptation to apneas with
      face immersion and erythrocyte release from the spleen. Twenty healthy
      volunteers, including ten splenectomized subjects, participated. After prone
      rest, they performed five maximal-duration apneas with face immersion in 10
      degrees C water, with 2-min intervals. Cardiorespiratory parameters and venous
      blood samples were collected. In subjects with spleens, hematocrit and hemoglobin
      concentration increased by 6.4% and 3.3%, respectively, over the serial apneas
      and returned to baseline 10 min after the series. A delay of the physiological
      breaking point of apnea, by 30.5% (17 s), was seen only in this group. These
      parameters did not change in the splenectomized group. Plasma protein
      concentration, preapneic alveolar PCO2, inspired lung volume, and diving
      bradycardia remained unchanged throughout the series in both groups. Serial
      apneas thus triggered the hematological changes that have been previously
      observed after long apneic diving shifts; they were rapidly reversed and did not
      occur in splenectomized subjects. This suggests that splenic contraction occurs
      in humans as a part of the diving response and may prolong repeated apneas.

PMID- 11247971
TI  - Three types of depolarization-activated potassium currents in acutely isolated
      mouse vestibular neurons.
AB  - The nature and electrophysiological properties of Ca(2+)-independent
      depolarization-activated potassium currents were investigated in vestibular
      primary neurons acutely isolated from postnatal mice using the whole cell
      configuration of the patch-clamp technique. Three types of currents were
      identified. The first current, sensitive to TEA (I(TEA)) and insensitive to 4
      aminopyridine (4-AP), activated at -40 mV and exhibited slow activation (tau(ac),
      38.4 +/- 7.8 ms at -30 mV, mean +/- SD). I(TEA) had a half activation potential
      [V(ac(1/2))] of -14.5 +/- 2.6 mV and was inactivated by up to 84.5 +/- 5.7% by 10
      s conditioning prepulses with a half inactivation potential [V(inac(1/2))] of 
      62.4 +/- 0.2 mV. The second current, sensitive to 4-AP (maximum block around 0.5
      mM) and to alpha-dendrotoxin (I(DTX)) appeared at -60 mV. Complete block of
      I(DTX) was achieved using either 20 nM alpha-DTX or 50 nM margatoxin. This
      current activated 10 times faster than I(TEA) (tau(ac), 3.5 +/- 0.8 ms at -50 mV)
      with V(ac(1/2)) of -51.2 +/- 0.6 mV, and inactivated only slightly compared with
      I(TEA) (maximum inactivation, 19.7 +/- 3.2%). The third current, also sensitive
      to 4-AP (maximum block at 2 mM), was selectively blocked by application of blood
      depressing substance (BDS-I; maximum block at 250 nM). The BDS-I-sensitive
      current (I(BDS-I)) activated around -60 mV. It displayed fast activation
      (tau(ac), 2.3 +/- 0.4 ms at -50 mV) and fast and complete voltage-dependent
      inactivation. I(BDS-I) had a V(ac(1/2)) of -31.3 +/- 0.4 mV and V(inac(1/2)) of 
      65.8 +/- 0.3 mV. It displayed faster time-dependent inactivation and recovery
      from inactivation than I(TEA). The three types of current were found in all the
      neurons investigated. Although I(TEA) was the major current, the proportion of
      I(DTX) and I(BDS-I) varied considerably between neurons. The ratio of the density
      of I(BDS-I) to that of I(DTX) ranged from 0.02 to 2.90 without correlation with
      the cell capacitances. In conclusion, vestibular primary neurons differ by the
      proportion rather than the type of the depolarization-activated potassium
      currents they express.

PMID- 11247972
TI  - Specific force of the rat extraocular muscles, levator and superior rectus,
      measured in situ.
AB  - Extraocular muscles are characterized by their faster rates of contraction and
      their higher resistance to fatigue relative to limb skeletal muscles. Another
      often reported characteristic of extraocular muscles is that they generate lower
      specific forces (sP(o), force per muscle cross-sectional area, kN/m(2)) than limb
      skeletal muscles. To investigate this perplexing issue, the isometric contractile
      properties of the levator palpebrae superioris (levator) and superior rectus
      muscles of the rat were examined in situ with nerve and blood supply intact. The
      extraocular muscles were attached to a force transducer, and the cranial nerves
      exposed for direct stimulation. After determination of optimal muscle length
      (L(o)) and stimulation voltage, a full frequency-force relationship was
      established for each muscle. Maximum isometric tetanic force (P(o)) for the
      levator and superior rectus muscles was 177 +/- 13 and 280 +/- 10 mN (mean +/-
      SE), respectively. For the calculation of specific force, a number of rat levator
      and superior rectus muscles were stored in a 20% nitric acid-based solution to
      isolate individual muscle fibers. Muscle fiber lengths (L(f)) were expressed as a
      percentage of overall muscle length, allowing a mean L(f) to L(o) ratio to be
      used in the estimation of muscle cross-sectional area. Mean L(f):L(o) was
      determined to be 0.38 for the levator muscle and 0.45 for the superior rectus
      muscle. The sP(o) for the rat levator and superior rectus muscles measured in
      situ was 275 and 280 kN/m(2), respectively. These values are within the range of
      sP(o) values commonly reported for rat skeletal muscles. Furthermore P(o) and
      sP(o) for the rat levator and superior rectus muscles measured in situ were
      significantly higher (P < 0.001) than P(o) and sP(o) for these muscles measured
      in vitro. The results indicate that the force output of intact extraocular
      muscles differs greatly depending on the mode of testing. Although in vitro
      evaluation of extraocular muscle contractility will continue to reveal important
      information about this group of understudied muscles, the lower sP(o) values of
      these preparations should be recognized as being significantly less than their
      true potential. We conclude that extraocular muscles are not intrinsically weaker
      than skeletal muscles.

PMID- 11247973
TI  - Whole muscle length-tension properties vary with recruitment and rate modulation
      in areflexive cat soleus.
AB  - The length-tension relationship is a fundamental property of muscle. In its
      classic form, which is used in muscle models incorporated into studies of motor
      control, the length-tension relationship is measured during maximal activation
      via tetanic electrical stimulation in whole muscles or during high intracellular
      calcium levels in single muscle fibers. In this study, we measured the length
      tension relationship of the cat soleus muscle during different levels of natural
      activation consisting of recruitment and rate modulation of motor units generated
      by the crossed extension reflex. The ipsilateral dorsal roots were cut to
      eliminate sensory feedback from the soleus. Length-tension was measured by large
      shortening steps that transiently allowed force to drop to zero. Force then
      recovered to a new steady value as the shorter length was maintained for several
      seconds. The effects of various levels of crossed extension activation on length
      tension were compared with direct electrical stimulation of the muscle at 5, 10,
      20, and 100 Hz. At all levels of crossed extension, the slope of the length
      tension function was much steeper than the slope for tetanic stimulation at 100
      Hz. Most slopes for crossed extension fell between the slopes seen with
      electrical stimulation at 10 and 20 Hz. There was a modest overall tendency for
      slope to decrease with the level of crossed extension activation. Because much of
      the normal movement repertoire requires submaximal activation, muscle models
      based on the tetanic length tension relationship will greatly underestimate the
      contribution of this relationship to force modulation at different muscle
      lengths.

PMID- 11247974
TI  - Temporal coding of contrast in primary visual cortex: when, what, and why.
AB  - How do neurons in the primary visual cortex (V1) encode the contrast of a visual
      stimulus? In this paper, the information that V1 responses convey about the
      contrast of static visual stimuli is explicitly calculated. These responses often
      contain several easily distinguished temporal components, which will be called
      latency, transient, tonic, and off. Calculating the information about contrast
      conveyed in each component and in groups of components makes it possible to
      delineate aspects of the temporal structure that may be relevant for contrast
      encoding. The results indicate that as much or more contrast-related information
      is encoded into the temporal structure of spike train responses as into the
      firing rate and that the temporally coded information is manifested most strongly
      in the latency to response onset. Transient, tonic, and off responses contribute
      relatively little. The results also reveal that temporal coding is important for
      distinguishing subtle contrast differences, whereas firing rates are useful for
      gross discrimination. This suggests that the temporal structure of neurons'
      responses may extend the dynamic range for contrast encoding in the primate
      visual system.

PMID- 11247975
TI  - Modulation by extracellular pH of low- and high-voltage-activated calcium
      currents of rat thalamic relay neurons.
AB  - The effects of changes in the extracellular pH (pH(o)) on low-voltage- (LVA) and
      high-voltage- (HVA) activated calcium currents of acutely isolated relay neurons
      of the ventrobasal thalamic complex (VB) were examined using the whole cell patch
      clamp technique. Modest extracellular alkalinization (pH 7.3 to 7.7) reversibly
      enlarged LVA calcium currents by 18.6 +/- 3.2% (mean +/- SE, n = 6), whereas
      extracellular acidification (pH 7.3 to 6.9) decreased the current by 24.8 +/-
      3.1% (n = 9). Normalized current amplitudes (I/I(7.3)) fitted as a function of
      pH(o) revealed an apparent pK(a) of 6.9. Both, half-maximal activation voltage
      and steady-state inactivation were significantly shifted to more negative
      voltages by 2-4 mV on extracellular alkalinization and to more positive voltages
      by 2-3 mV on extracellular acidification, respectively. Recovery from
      inactivation of LVA calcium currents was not significantly affected by changes in
      pH(o). In contrast, HVA calcium currents were less sensitive to changes in pH(o).
      Although extracellular alkalinization increased maximal HVA current by 6.0 +/-
      2.0% (n = 7) and extracellular acidification decreased it by 11.9 +/- 0.02% (n =
      11), both activation and steady-state inactivation were only marginally affected
      by the moderate changes in pH(o) used in the present study. The results show that
      calcium currents of thalamic relay neurons exhibit different pH(o) sensitivity.
      Therefore activity-related extracellular pH transients might selectively modulate
      certain aspects of the electrogenic behavior of thalamic relay neurons.

PMID- 11247976
TI  - Damping actions of the neuromuscular system with inertial loads: human flexor
      pollicis longus muscle.
AB  - Our previous work in an animal model showed that neuromuscular damping properties
      help maintain limb posture by effectively dissipating mechanical energy arising
      from disturbances. The purpose of this study was to determine whether similar
      damping properties were expressed in intact, normal human muscles. To review
      briefly, when the reflexively active soleus muscle in a decerebrate cat is
      coupled to an inertial load, application of a force impulse to the load results
      in lightly damped oscillations. By calculating the logarithmic decrement in
      muscle velocity following the impulse (the decrement being related to the amount
      of energy dissipated from the inertia), we found that damping increased with
      oscillation amplitude, a nonlinear property. This nonlinearity represents an
      automatic compensation for larger perturbations. Our findings in parallel
      experiments on the interphalangeal joint of the human thumb were that the long
      thumb flexor, the flexor pollicis longus (FPL), displayed mechanical and reflex
      behavior closely comparable to that reported earlier for the cat soleus, despite
      differences in architectural and metabolic properties between these muscles.
      Specifically, by selecting experimental trials that did not include voluntary
      interventions, we observed amplitude-dependent differences in damping in which
      larger amplitude movements elicited larger damping than did smaller movements. In
      addition, even after accounting for amplitude-dependent differences in damping,
      damping was found to be larger in later cycles than in the first cycle. This
      nonlinearity indicates that both mechanical properties of muscle and reflex
      mechanisms are dependent on prior movement history. We propose that this history
      dependent behavior arises from the effects of prior movement on stretch reflex
      gain, and these effects are mediated primarily via changes in muscle spindle
      properties. Recordings of electromyographic activity from the FPL, during the
      first and second cycles of oscillation supported this postulate of a reduced
      reflex gain following prior motion. The functional significance of these
      nonlinear damping properties is that during the initial muscle stretch, the
      stiffness is high, which helps to preserve the initial position (although at the
      expense of promoting oscillation). Subsequently, the ensuing increase in damping
      helps suppress continuing oscillation. This sequence of varying mechanical
      properties is broadly analogous to the features of a predictive, or feed-forward
      controller, designed to produce a response that initially maintains position, and
      subsequently dampens oscillations. These results show that the intrinsic
      properties of muscle and spinal reflexes automatically provide a complex time
      varying response, appropriate for maintenance of stable limb posture.

PMID- 11247978
TI  - Plasticity of bat's central auditory system evoked by focal electric stimulation
      of auditory and/or somatosensory cortices.
AB  - Recent findings indicate that the corticofugal system would play an important
      role in cortical plasticity as well as collicular plasticity. To understand the
      role of the corticofugal system in plasticity, therefore, we studied the amount
      and the time course of plasticity in the inferior colliculus (IC) and auditory
      cortex (AC) evoked by focal electrical stimulation of the AC and also the effect
      of electrical stimulation of the somatosensory cortex on the plasticity evoked by
      the stimulation of the AC. In adult big brown bats (Eptesicus fuscus), we made
      the following major findings. 1) Electric stimulation of the AC evokes best
      frequency (BF) shifts, i.e., shifts in frequency-response curves of collicular
      and cortical neurons. These BF shifts start to occur within 2 min, reach a
      maximum (or plateau) at 30 min, and then recover approximately 180 min after a 30
      min-long stimulus session. When the stimulus session is lengthened from 30 to 90
      min, the plateau lasts approximately 60 min, but BF shifts recover approximately
      180 min after the session. 2) The electric stimulation of the somatosensory
      cortex delivered immediately after that of the AC, as in fear conditioning,
      evokes a dramatic lengthening of the recovery period of the cortical BF shifts
      but not that of the collicular BF shift. The electric stimulation of the
      somatosensory cortex delivered before that of the AC, as in backward
      conditioning, has no effect on the collicular and cortical BF shifts. 3) Electric
      stimulation of the AC evokes BF shifts not only in the ipsilateral IC and AC but
      also in the contralateral IC and AC. BF shifts are smaller in amount and shorter
      in recovery time for contralateral collicular and cortical neurons than for
      ipsilateral ones. Our findings support the hypothesis that the AC and the
      corticofugal system have an intrinsic mechanism for reorganization of the IC and
      AC, that the reorganization is highly specific to a value of an acoustic
      parameter (frequency), and that the reorganization is augmented by excitation of
      nonauditory sensory cortex that makes the acoustic stimulus behaviorally relevant
      to the animal through associative learning.

PMID- 11247977
TI  - Excitatory synaptic input to granule cells increases with time after kainate
      treatment.
AB  - Temporal lobe epilepsy is usually associated with a latent period and an
      increased seizure frequency following a precipitating insult. After kainate
      treatment, the mossy fibers of the dentate gyrus are hypothesized to form
      recurrent excitatory circuits between granule cells, thus leading to a
      progressive increase in the excitatory input to granule cells. Three groups of
      animals were studied as a function of time after kainate treatment: 1-2 wk, 2-4
      wk, and 10-51 wk. All the animals studied 10-51 wk after kainate treatment were
      observed to have repetitive spontaneous seizures. Whole cell patch-clamp
      recordings in hippocampal slices showed that the amplitude and frequency of
      spontaneous excitatory postsynaptic currents (EPSCs) in granule cells increased
      with time after kainate treatment. This increased excitatory synaptic input was
      correlated with the intensity of the Timm stain in the inner molecular layer
      (IML). Flash photolysis of caged glutamate applied in the granule cell layer
      evoked repetitive EPSCs in 10, 32, and 66% of the granule cells at the different
      times after kainate treatment. When inhibition was reduced with bicuculline,
      photostimulation of the granule cell layer evoked epileptiform bursts of action
      potentials only in granule cells from rats 10-51 wk after kainate treatment.
      These data support the hypothesis that kainate-induced mossy fiber sprouting in
      the IML results in the progressive formation of aberrant excitatory connections
      between granule cells. They also suggest that the probability of occurrence of
      electrographic seizures in the dentate gyrus increases with time after kainate
      treatment.

PMID- 11247979
TI  - Neonatal deafferentation does not alter membrane properties of trigeminal nucleus
      principalis neurons.
AB  - In the brain stem trigeminal complex of rats and mice, presynaptic afferent
      arbors and postsynaptic target cells form discrete modules ("barrelettes"), the
      arrangement of which duplicates the patterned distribution of whiskers and sinus
      hairs on the ipsilateral snout. Within the barrelette region of the nucleus
      principalis of the trigeminal nerve (PrV), neurons participating in barrelettes
      and those with dendritic spans covering multiple barrelettes (interbarrelette
      neurons) can be identified by their morphological and electrophysiological
      characteristics as early as postnatal day 1. Barrelette cells have focal
      dendritic processes, are characterized by a transient K(+) conductance (I(A)),
      whereas interbarrelette cells with larger soma and extensive dendritic fields
      characteristically exhibit low-threshold T-type Ca(2+) spikes (LTS). In this
      study, we surveyed membrane properties of barrelette and interbarrelette neurons
      during and after consolidation of barrelettes in the PrV and effects of
      peripheral deafferentation on these properties. During postnatal development
      (PND1-13), there were no changes in the resting potential, composition of active
      conductances and Na(+) spikes of both barrelette and interbarrelette cells. The
      only notable changes were a decline in input resistance and a slight increase in
      the amplitude of LTS. The infraorbital (IO) branch of the trigeminal nerve
      provides the sole afferent input source to the whisker pad. IO nerve transection
      at birth abolishes barrelette formation as well as whisker-related neuronal
      patterns all the way to the neocortex. Surprisingly this procedure had no effect
      on membrane properties of PrV neurons. The results of the present study
      demonstrate that distinct membrane properties of barrelette and interbarrelette
      cells are maintained even in the absence of input from the whiskers during the
      critical period of pattern formation.

PMID- 11247981
TI  - Burst and tonic response modes in thalamic neurons during sleep and wakefulness.
AB  - Thalamic neurons can exhibit two distinct firing modes: tonic and burst. In the
      lateral geniculate nucleus (LGN), the tonic mode appears as a relatively faithful
      relay of visual information from retina to cortex. The function of the burst mode
      is less understood. Its prevalence during slow-wave sleep (SWS) and linkage to
      synchronous cortical electroencephalogram (EEG) suggest that it has an important
      role during this form of sleep. Although not nearly as common, bursting can also
      occur during wakefulness. The goal of this study was to identify conditions that
      affect burst probability, and to compare burst incidence during sleeping and
      waking. LGN neurons are extraordinarily heterogenous in the degree to which they
      burst, during both sleeping and waking. Some LGN neurons never burst under any
      conditions during wakefulness, and several never burst during slow-wave sleep.
      During wakefulness, <1% of action potentials were associated with bursting,
      whereas during sleep this fraction jumps to 18%. Although bursting was most
      common during slow-wave sleep, more than 50% of the bursting originated from 14%
      of the LGN cells. Bursting during sleep was largely restricted to episodes
      lasting 1-5 s, with approximately 47% of these episodes being rhythmic and in the
      delta frequency range (0.5-4 Hz). In wakefulness, although visual stimulation
      accounted for the greatest number of bursts, it was still a small fraction of the
      total response (4%, 742 bursts/17,744 cycles in 93 cells). We identified two
      variables that appeared to influence burst probability: size of the visual
      stimuli used to elicit responses and behavioral state. Increased stimulus size
      increased burst probability. We attribute this to the increased influence large
      stimuli have on a cell's inhibitory mechanisms. As with sleep, a large fraction
      of bursting originated from a small number of cells. During visual stimulation,
      50% of bursting was generated by 9% of neurons. Increased vigilance was
      negatively correlated with burst probability. Visual stimuli presented during
      active fixation (i.e., when the animal must fixate on an overt fixation point)
      were less likely to produce bursting, than when the same visual stimuli were
      presented but no fixation point present ("passive" fixation). Such observations
      suggest that even brief departures from attentive states can hyperpolarize
      neurons sufficiently to de-inactivate the burst mechanism. Our results provide a
      new view of the temporal structure of bursting during slow-wave sleep; one that
      supports episodic rhythmic activity in the intact animal. In addition, because
      bursting could be tied to specific conditions within wakefulness, we suggest that
      bursting has a specific function within that state.

PMID- 11247980
TI  - beta-NAAG rescues LTP from blockade by NAAG in rat dentate gyrus via the type 3
      metabotropic glutamate receptor.
AB  - N-Acetylaspartylglutamate (NAAG) is an agonist at the type 3 metabotropic
      glutamate receptor (mGluR3), which is coupled to a Gi/o protein. When activated,
      the mGluR3 receptor inhibits adenylyl cyclase and reduces the cAMP-mediated
      second-messenger cascade. Long-term potentiation (LTP) in the medial perforant
      path (MPP) of the hippocampal dentate gyrus requires increases in cAMP. The
      presence of mGluR3 receptors and NAAG in neurons of the dentate gyrus suggests
      that this peptide transmitter may inhibit LTP in the dentate gyrus. High
      frequency stimulation (100 Hz; 2 s) of the MPP resulted in LTP of extracellularly
      recorded excitatory postsynaptic potentials at the MPP-granule cell synapse of
      rat hippocampal slices. Perfusion of the slice with NAAG (50 and 200 microM)
      blocked LTP. Neither 50 nor 200 microM NAAG produced N-methyl-D-aspartate
      receptor currents in the granule cells of the acute hippocampal slice. The group
      II mGluR antagonist ethyl glutamate (100 microM) and a structural analogue of
      NAAG, beta-NAAG (100 microM), prevented the blockade of LTP by NAAG. Paired-pulse
      depression of the excitatory postsynaptic potential at 20- and 80-ms interpulse
      intervals (IPI) was not affected by NAAG or beta-NAAG. beta-NAAG did not affect
      inositol trisphosphate production stimulated by the agonist glutamate in cells
      expressing the group I mGluR1alpha or mGluR5. beta-NAAG blocked the decrease in
      forskolin-stimulated cAMP by the group II mGluR agonist (2S,2'R,3'R)-2-(2',3'
      dicarboxycyclopropyl)glycine (DCG-IV) but not the group III mGluR agonist L(+)-2
      amino-4-phosphonobutyric acid in cerebellar granule cells. In cells transfected
      with mGluR3, but not mGluR2, beta-NAAG blocked forskolin-stimulated cAMP
      responses to glutamate, NAAG, the nonspecific group I, II agonist trans-ACPD, and
      the group II agonist DCG-IV. We conclude that beta-NAAG is a selective mGluR
      antagonist capable of differentiating between mGluR2 and mGluR3 subtypes and that
      the mGluR3 receptor functions to regulate activity-dependent synaptic
      potentiation in the hippocampus.

PMID- 11247982
TI  - Visual influences on the development and recovery of the vestibuloocular reflex
      in the chicken.
AB  - Whenever the head turns, the vestibuloocular reflex (VOR) produces compensatory
      eye movements to help stabilize the image of the visual world on the retina.
      Uncompensated slip of the visual world across the retina results in a gradual
      change in VOR gain to minimize the image motion. VOR gain changes naturally
      during normal development and during recovery from neuronal damage. We ask here
      whether visual slip is necessary for the development of the chicken VOR (as in
      other species) and whether it is required for the recovery of the VOR after hair
      cell loss and regeneration. In the first experiment, chickens were reared under
      stroboscopic illumination, which eliminated visual slip. The horizontal and
      vertical VORs (h- and vVORs) were measured at different ages and compared with
      those of chickens reared in normal light. Strobe-rearing prevented the normal
      development of both h- and vVORs. After 8 wk of strobe-rearing, 3 days of
      exposure to normal light caused the VORs to recover partially but not to normal
      values. In the second experiment, 1-wk-old chicks were treated with streptomycin,
      which destroys most vestibular hair cells and reduces hVOR gain to zero. In
      birds, vestibular hair cells regenerate so that after 8 wk in normal illumination
      they appear normal and hVOR gain returns to values that are normal for birds of
      that age. The treated birds in this study recovered in either normal or
      stroboscopic illumination. Their hVOR and vVOR and vestibulocollic reflexes (VCR)
      were measured and compared with those of untreated, age-matched controls at 8 wk
      posthatch, when hair cell regeneration is known to be complete. As in previous
      studies, the gain of the VOR decreased immediately to zero after streptomycin
      treatment. After 8 wk of recovery under normal light, the hVOR was normal, but
      vVOR gain was less than normal. After 8 wk of recovery under stroboscopic
      illumination, hVOR gain was less than normal at all frequencies. VCR recovery was
      not affected by the strobe environment. When streptomycin-treated, strobe
      recovered birds were then placed in normal light for 2 days, hVOR gain returned
      to normal. Taken together, the results of these experiments suggest that
      continuous visual feedback can adjust VOR gain. In the absence of appropriate
      visual stimuli, however, there is a default VOR gain and phase to which birds
      recover or revert, regardless of age. Thus an 8-wk-old chicken raised in a strobe
      environment from hatch would have the same gain as a streptomycin-treated chicken
      that recovers in a strobe environment.

PMID- 11247983
TI  - Short-latency disparity vergence in humans.
AB  - Eye movement recordings from humans indicated that brief exposures (200 ms) to
      horizontal disparity steps applied to large random-dot patterns elicit horizontal
      vergence at short latencies (80.9 +/- 3.9 ms, mean +/- SD; n = 7). Disparity
      tuning curves, describing the dependence of the initial vergence responses
      (measured over the period 90-157 ms after the step) on the magnitude of the
      steps, resembled the derivative of a Gaussian, with nonzero asymptotes and a
      roughly linear servo region that extended only a degree or two on either side of
      zero disparity. Responses showed transient postsaccadic enhancement: disparity
      steps applied in the immediate wake of saccadic eye movements yielded higher
      vergence accelerations than did the same steps applied some time later (mean time
      constant of the decay, 200 ms). This enhancement seemed to be dependent, at least
      in part, on the visual reafference associated with the prior saccade because
      similar enhancement was observed when the disparity steps were applied in the
      wake of saccadelike shifts of the textured pattern. Vertical vergence responses
      to vertical disparity steps were qualitatively similar: latencies were longer (on
      average, by 3 ms), disparity tuning curves had the same general form but were
      narrower (by approximately 20%), and their peak-to-peak amplitudes were smaller
      (by approximately 70%). Initial vergence responses usually had directional errors
      (orthogonal components) with a very systematic dependence on step size that often
      approximated an exponential decay to a nonzero asymptote (mean space constant +/-
      SD, 1.18 +/- 0.66 degrees ). Based on the asymptotes of these orthogonal
      responses, horizontal errors (with vertical steps) were on average more than
      three times greater than vertical errors (with horizontal steps). Disparity steps
      >7 degrees generated "default" responses that were independent of the direction
      of the step, idiosyncratic, and generally had both horizontal and vertical
      components. We suggest that the responses depend on detectors that sense local
      disparity matches, and that orthogonal and "default" responses result from
      globally "false" matches. Recordings from three monkeys, using identical
      disparity stimuli, confirmed that monkeys also show short-latency disparity
      vergence responses (latency approximately 25 ms shorter than that of humans), and
      further indicated that these responses show all of the major features seen in
      humans, the differences between the two species being solely quantitative. Based
      on these data and those of others implying that foveal images normally take
      precedence, we suggest that the mechanisms under study here ordinarily serve to
      correct small vergence errors, automatically, especially after saccades.

PMID- 11247984
TI  - Kappa opioid receptor inhibition of glutamatergic transmission in the nucleus
      accumbens shell.
AB  - Microinjection of kappa-opioid receptor agonists into the nucleus accumbens
      produces conditioned place aversion. While attention has focused primarily on the
      inhibition of dopamine release by kappa-receptor agonists as the synaptic
      mechanism underlying this effect, recent anatomical studies have raised the
      possibility that regulation of noncatecholaminergic transmission also contribute.
      We have investigated the effects of kappa-receptor activation on fast excitatory
      synaptic transmission in an in vitro slice preparation using whole cell voltage
      clamp or extracellular field recordings in the shell region of the nucleus
      accumbens. The kappa-receptor agonist U69593 produces a pronounced, dose
      dependent inhibition of glutamatergic excitatory postsynaptic currents (EPSCs)
      that can be reversed by 100 nM nor-BNI. Furthermore, U69593 causes an increase in
      the paired-pulse ratio as well as a decrease in the frequency of spontaneous
      miniature events, suggesting a presynaptic site of action. Despite anatomical
      evidence for kappa-receptor localization on dendritic spines of nucleus accumbens
      neurons, no electrophysiological evidence of a postsynaptic effect was found.
      This presynaptic inhibition of excitatory synaptic transmission in the nucleus
      accumbens shell provides a novel mechanism that may contribute to the kappa
      receptor-mediated aversion observed in intact animals.

PMID- 11247985
TI  - Hypoglycemia enhances ionotropic but reduces metabotropic glutamate responses in
      substantia nigra dopaminergic neurons.
AB  - It is widely accepted that energy deprivation causes a neuronal death that is
      mainly determined by an increase in the extracellular level of glutamate.
      Consequently an excessive membrane depolarization and a rise in the intracellular
      concentration of sodium and calcium are produced. In spite of this scenario, the
      function of excitatory and inhibitory amino acids during an episode of energy
      failure has not been studied yet at a cellular level. In a model of cerebral
      hypoglycemia in the rat substantia nigra pars compacta, we measured neuronal
      responses to excitatory amino acid agonists. Under single-electrode voltage-clamp
      mode at -60 mV, the application of the ionotropic glutamate receptor agonists N
      methyl-D-aspartate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid,
      kainate, and the metabotropic group I agonist (S)-3,5-dihydroxyphenilglycine
      (DHPG) produced reversible inward currents in the dopaminergic cells. In
      addition, an outward current was caused by the superfusion of the metabotropic
      GABA(B) agonist baclofen. Glucose deprivation enhanced the inward responses
      caused by each ionotropic glutamate agonist. In contrast, hypoglycemia depressed
      the DHPG-induced inward current and the baclofen-induced outward current. These
      effects of hypoglycemia were reversible. To test whether a failure of the
      Na(+)/K(+) ATPase pump could account for the modification of the agonist-induced
      currents during hypoglycemia, we treated the midbrain slices with strophanthidin
      (1-3 microM). Strophanthidin enhanced the inward currents caused by glutamate
      agonists. However, it did not modify the GABA(B)-induced outward current. Our
      data suggest that glucose deprivation enhances the inward current caused by the
      stimulation of ionotropic glutamate receptors while it dampens the responses
      caused by the activation of metabotropic receptors. Thus a substantial component
      of the augmented neuronal response to glutamate, during energy deprivation, is
      very likely due to the failure of Na(+) and Ca(2+) extrusion and might ultimately
      favor excitotoxic processes in the dopaminergic cells.

PMID- 11247986
TI  - Encoding of different aspects of afferent activities by two types of cells in the
      corpus glomerulosum of a teleost brain.
AB  - The corpus glomerulosum (CG) is an expansive nucleus in acanthopterigian teleosts
      that has been suggested to be involved in vision-related information processing
      and the control of the hypothalamic function. The CG has only two types of
      constituent cells, the large cell and the small cell, and well-defined
      afferent/efferent fiber connections. One of the three types of teleostean CG,
      type III has additional outstanding morphological characters: clearly laminated
      organization and giant (>50 microm in diameter) tips of postsynaptic dendrites.
      Although such histological architecture is potentially advantageous for the study
      of information processing in a brain nucleus based on the physiological
      properties of identified cells and synapses, previous studies on the CG have been
      limited to anatomy. In this study, we developed a slice preparation of the type
      III CG in a teleost, Stephanoplepis cirrhifer, and studied the morphology and
      physiology of individual cells and synaptic transmission by means of dendritic
      intracellular and somatic whole cell recordings. The characteristic morphology of
      the two types of cells was revealed by intracellular staining. While both of them
      received similar glutamatergic and GABAergic projections from the nucleus
      corticalis mediated by AMPA, N-methyl-D-aspartate, and GABA(A) receptors, they
      showed quite distinctive firing properties and postsynaptic responses with
      current injection and synaptic inputs: the large cell fired a single spike, and
      the small cell fired a spike train whose frequency was dependent on the stimulus
      intensity. Furthermore, the large cell showed low-pass temporal filtering
      properties with paired stimuli. These results suggest that the large cell and the
      small cell may encode different aspects of the corticalis activities.

PMID- 11247987
TI  - Differential regulation of cutaneous and H-reflexes during leg cycling in humans.
AB  - Reflexes undergo modulation according to task and timing during standing,
      walking, running, and leg cycling in humans. Both cutaneous and Hoffman (H-)
      reflexes are modulated by movement and task. However, recent evidence suggests
      that the modulation pattern for cutaneous and H-reflexes may be different. We
      sought to clarify this issue by reducing the effect of movement phase and
      altering the level of background muscle activation (low and high) in static and
      dynamic (leg cycling) conditions. Electromyography was recorded from the ankle
      extensors soleus and medial gastrocnemius (MG) and the knee extensor vastus
      lateralis (VL). Reflexes were evoked during the downstroke of stationary leg
      cycling. Cutaneous reflexes were evoked with trains of 5 x 1.0 ms pulses at 300
      Hz delivered to the distal tibial nerve, whereas H-reflexes were evoked in soleus
      by stimulation with single 1.0-ms pulses. There were two main observations in
      this study: 1) middle latency cutaneous reflexes were facilitatory during static
      contraction but were dramatically attenuated or reversed to suppressive responses
      during cycling (task-dependent modulation); 2) soleus H-reflexes were larger in
      the high muscle activation condition but were unaffected by task (no task
      dependent modulation). Thus opposite results were obtained in the two reflex
      pathways. It is concluded that cutaneous and H-reflexes are modulated by
      different mechanisms during active locomotor-like movements.

PMID- 11247988
TI  - Zinc-induced augmentation of excitatory synaptic currents and glutamate receptor
      responses in hippocampal CA3 neurons.
AB  - Zinc is found throughout the CNS at synapses co-localized with glutamate in
      presynaptic terminals. In particular, dentate granule cells' (DGC) mossy fiber
      (MF) axons contain especially high concentrations of zinc co-localized with
      glutamate within vesicles. To study possible physiological roles of zinc,
      visualized slice-patch techniques were used to voltage-clamp rat CA3 pyramidal
      neurons, and miniature excitatory postsynaptic currents (mEPSCs) were isolated.
      Bath-applied zinc (200 microM) enhanced median mEPSC peak amplitudes to 153.0% of
      controls, without affecting mEPSC kinetics. To characterize this augmentation
      further, rapid agonist application was performed on perisomatic outside-out
      patches to coapply zinc with glutamate extremely rapidly for brief (1 ms)
      durations, thereby emulating release kinetics of these substances at excitatory
      synapses. When zinc was coapplied with glutamate, zinc augmented peak glutamate
      currents (mean +/- SE, 116.6 +/- 2.8% and 143.8 +/- 9.8% of controls at 50 and
      200 microM zinc, respectively). This zinc-induced potentiation was concentration
      dependent, and pharmacological isolation of alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) receptor-mediated currents (AMPAR currents) gave
      results similar to those observed with glutamate application (mean, 115.0 +/-
      5.4% and 132.5 +/- 9.1% of controls at 50 and 200 microM zinc, respectively).
      Inclusion of the AMPAR desensitization blocker cyclothiazide in the control
      solution, however, abolished zinc-induced augmentation of glutamate-evoked
      currents, suggesting that zinc may potentiate AMPAR currents by inhibiting AMPAR
      desensitization. Based on the results of the present study, we hypothesize that
      zinc is a powerful modulator of both excitatory synaptic transmission and
      glutamate-evoked currents at physiologically relevant concentrations. This
      modulatory role played by zinc may be a significant factor in enhancing
      excitatory neurotransmission and could significantly regulate function at the
      mossy fiber-CA3 synapse.

PMID- 11247989
TI  - Serine/threonine protein phosphatases and synaptic inhibition regulate the
      expression of cholinergic-dependent plateau potentials.
AB  - We previously identified cholinergic-dependent plateau potentials (PPs) in CA1
      pyramidal neurons that were intrinsically generated by interplay between voltage
      gated calcium entry and a Ca(2+)-activated nonselective cation conductance. In
      the present study, we examined both the second-messenger pathway and the role of
      synaptic inhibition in the expression of PPs. The stimulation of m1/m3
      cholinergic receptor subtypes and G-proteins were critical for activating PPs
      because selective receptor antagonists (pirenzepine, hexahydro-sila-difenidol
      hydrochloride, 4-diphenylacetoxy-N-methylpiperidine methiodide) and intracellular
      guanosine-5'-O-(2-thiodiphosphate) prevented PP generation in carbachol. Intense
      synaptic stimulation occasionally activated PPs in the presence of oxytremorine
      M, a cholinergic agonist with preference for m1/m3 receptors. PPs were
      consistently activated by synaptic stimulation only when oxytremorine M was
      combined with antagonists at both GABA(A) and GABA(B) receptors. These latter
      data indicate an important role for synaptic inhibition in preventing PP
      generation. Both intrinsically generated and synaptically activated PPs could not
      be elicited following inhibition of serine/threonine protein phosphatases by
      calyculin A, okadaic acid, or microcystin-L, suggesting that muscarinic-induced
      dephosphorylation is necessary for PP generation. PP genesis was also inhibited
      following irreversible thiophosphorylation by intracellular perfusion with ATP
      gamma-S. These data indicate that the expression of cholinergic-dependent PPs
      requires protein phosphatase-induced dephosphorylation via G-protein-linked m1/m3
      receptor(s). Moreover, synaptic inhibition via both GABA(A) and GABA(B) receptors
      normally prevents the synaptic activation of PPs. Understanding the regulation of
      PPs should provide clues to the role of this regenerative potential in both
      normal activity and pathophysiological processes such as epilepsy.

PMID- 11247990
TI  - Temporal representation of iterated rippled noise as a function of delay and
      sound level in the ventral cochlear nucleus.
AB  - The discharge patterns of single units in the ventral cochlear nucleus (VCN) of
      anesthetized guinea pigs were examined in response to iterated rippled noise
      (IRN) as a function of the IRN delay (which determines the IRN pitch) and the IRN
      sound level. Delays were varied over five octaves in half-octave steps, and sound
      levels were varied over a 30- or 50-dB range in steps of 5 dB. Neural responses
      were analyzed in terms of first-order and all-order inter-spike intervals (ISIs).
      The IRN quasi-periodicity was preserved in the all-order ISIs for most units
      independent of unit type or best frequency (BF). A deterioration of the temporal
      all-order code was found, however, when the neural response was influenced by
      inhibition. The IRN quasi-periodicity was also preserved in first-order ISIs for
      a limited range of IRN delays and levels. Sustained Chopper units (CS) in the VCN
      responded with very regular ISIs when the IRN delay corresponded to the unit's
      chopping period; i.e., the unit showed an increased proportion of intervals
      corresponding to the IRN delay (interval enhancement) relative to an equal-level,
      white-noise stimulation. This interval enhancement has a band-pass characteristic
      with a peak corresponding to the chopping period. Moreover, for CS units in rate
      saturation, the chopping period, and thus the interval enhancement to the IRN,
      did not vary with level. Units classified as onset-chopper also show a band-pass
      interval enhancement to the IRN stimuli; however, they show more level-dependent
      changes than CS units. Primary-like (PL) units also show level-dependent changes
      in their ability to code the IRN pitch in first-order intervals. The range of
      delays where PL units showed interval enhancement was broader and extended to
      shorter delays. Based on these findings, it is suggested that CS units may play
      an important role in pitch processing in that they transform a higher-order
      interval code into a first-order interval place code. Their limited dynamic range
      together with the preservation of the temporal stimulus features in saturation
      may serve as a physiological basis for the perceived level independence of pitch.

PMID- 11247991
TI  - Spectro-temporal response field characterization with dynamic ripples in ferret
      primary auditory cortex.
AB  - To understand the neural representation of broadband, dynamic sounds in primary
      auditory cortex (AI), we characterize responses using the spectro-temporal
      response field (STRF). The STRF describes, predicts, and fully characterizes the
      linear dynamics of neurons in response to sounds with rich spectro-temporal
      envelopes. It is computed from the responses to elementary "ripples," a family of
      sounds with drifting sinusoidal spectral envelopes. The collection of responses
      to all elementary ripples is the spectro-temporal transfer function. The complex
      spectro-temporal envelope of any broadband, dynamic sound can expressed as the
      linear sum of individual ripples. Previous experiments using ripples with
      downward drifting spectra suggested that the transfer function is separable,
      i.e., it is reducible into a product of purely temporal and purely spectral
      functions. Here we measure the responses to upward and downward drifting ripples,
      assuming reparability within each direction, to determine if the total
      bidirectional transfer function is fully separable. In general, the combined
      transfer function for two directions is not symmetric, and hence units in AI are
      not, in general, fully separable. Consequently, many AI units have complex
      response properties such as sensitivity to direction of motion, though most
      inseparable units are not strongly directionally selective. We show that for most
      neurons, the lack of full separability stems from differences between the upward
      and downward spectral cross-sections but not from the temporal cross-sections;
      this places strong constraints on the neural inputs of these AI units.

PMID- 11247992
TI  - Cellular mechanisms of thalamically evoked gamma oscillations in auditory cortex.
AB  - The purpose of this study was to clarify the neurogenesis of thalamically evoked
      gamma frequency (approximately 40 Hz) oscillations in auditory cortex by
      comparing simultaneously recorded extracellular and intracellular responses
      elicited with electrical stimulation of the posterior intralaminar nucleus of the
      thalamus (PIL). The focus of evoked gamma activity was located between primary
      and secondary auditory cortex using a 64-channel epipial electrode array, and all
      subsequent intracellular recordings and single-electrode field potential
      recordings were made at this location. These data indicate that PIL stimulation
      evokes gamma oscillations in auditory cortex by tonically depolarizing pyramidal
      cells in the supra- and infragranular layers. No cells revealed endogenous
      membrane properties capable of producing activity in the gamma frequency band
      when depolarized individually with injected current, but all displayed both sub-
      and supra-threshold responses time-locked to extracellular fast oscillations when
      the population was depolarized by PIL stimulation. We propose that cortical gamma
      oscillations may be produced and propagated intracortically by network
      interactions among large groups of neurons when mutually excited by modulatory
      input from the intralaminar thalamus and that these oscillations do not require
      specialized pacemaker cells for their neurogenesis.

PMID- 11247993
TI  - Synaptic and nonsynaptic contributions to giant ipsps and ectopic spikes induced
      by 4-aminopyridine in the hippocampus in vitro.
AB  - Hippocampal slices bathed in 4-aminopyridine (4-AP, < or =200 microM) exhibit 1)
      spontaneous large inhibitory postsynaptic potentials (IPSPs) in pyramidal cells,
      which occur without the necessity of fast glutamatergic receptors, and which
      hence are presumed to arise from coordinated firing in populations of
      interneurons; 2) spikes of variable amplitude, presumed to be of antidromic
      origin, in some pyramidal cells during the large IPSP; 3) bursts of action
      potentials in selected populations of interneurons, occurring independently of
      fast glutamatergic and of GABA(A) receptors. We have used neuron pairs, and a
      large network model (3,072 pyramidal cells, 384 interneurons), to examine how
      these phenomena might be inter-related. Network bursts in electrically coupled
      interneurons have previously been shown to be possible with dendritic gap
      junctions, when the dendrites were capable of spike initiation, and when action
      potentials could cross from cell to cell via gap junctions; recent experimental
      data showing that dendritic gap junctions between cortical interneurons lead to
      coupling potentials of only about 0.5 mV argue against this mechanism, however.
      We now show that axonal gap junctions between interneurons could also lead to
      network bursts; this concept is consistent with the occurrence of spikelets and
      partial spikes in at least some interneurons in 4-AP. In our model, spontaneous
      antidromic action potentials can induce spikelets and action potentials in
      principal cells during the large IPSP. The probability of observing this type of
      activity increases significantly when axonal gap junctions also exist between
      pyramidal cells. Sufficient antidromic activity in the model can lead to
      epileptiform bursts, independent of alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors, in some
      principal cells, preceded by IPSPs and spikelets. The model predicts that gap
      junction blockers should suppress large IPSPs observed in 4-AP and should also
      reduce the probability of observing antidromic activity, or bursting, in
      pyramidal cells. Experiments show that, indeed, the gap junction blocking
      compound carbenoxolone does suppress spontaneous large IPSCs, occurring in 4-AP
      plus ionotropic glutamate blockers, together with a GABA(B) receptor blocker;
      carbenoxolone also suppresses large, fast inward currents, corresponding to
      ectopic spikes, which occur in 4-AP. Carbenoxolone does not suppress large
      depolarizing IPSPs induced by tetanic stimulation. We conclude that in 4-AP,
      axonal gap junctions could, at least in principle, account in part for both the
      large IPSPs, and for the antidromic activity in pyramidal neurons.

PMID- 11247994
TI  - Unilateral hearing losses alter loud sound-induced temporary threshold shifts and
      efferent effects in the normal-hearing ear.
AB  - In animals with bilaterally normal hearing, olivocochlear pathways can protect
      the cochlea from the temporary shifts in hearing sensitivity (temporary threshold
      shifts; TTSs) caused by short-duration intense loud sounds. The crossed
      olivocochlear pathway provides protection during binaural loud sound, and
      uncrossed pathways protect when monaural or binaural loud sounds occur in noise
      backgrounds. Here I demonstrate that when there is a chronic unilateral hearing
      loss, effects of loud sounds, and efferent effects on loud sound, in the normal
      hearing ear differ markedly from normal. Three categories of test animals with
      unilateral hearing loss were tested for effects at the normal-hearing ear. In all
      categories a monaural loud tone to the normal-hearing ear produced lower-than
      normal TTSs, apparently because of a tonic re-setting of that ear's
      susceptibility to loud sound. Second, in the two test categories in which the
      hearing-loss ear was only partly damaged, binaural loud sound exacerbated TTSs in
      the normal-hearing ear because it caused threshold shifts that were a combination
      of "pure" TTSs and uncrossed efferent suppression of cochlear sensitivity. (In
      normal cats, this binaural tone results in crossed olivocochlear protection that
      reduces TTS.) Binaural loud sound did not produce such uncrossed efferent effects
      in the test category in which the nontest ear had suffered total hearing loss,
      suggesting that this uncrossed efferent effect required binaural input to the
      CNS. It is noteworthy that, in the absence of this uncrossed efferent
      suppression, the pure loud sound-alone induced TTSs after binaural exposure were
      low. Thus in the absence of any efferent effect, the normal-hearing cochlea had a
      reduced susceptibility to loud tone-induced damage. Finally, the results suggest
      that, with respect to cochlear actions at high sound levels, uncrossed and
      crossed efferent pathways may exert different effects at the one type of receptor
      cell.

PMID- 11247995
TI  - Adrenergic hyperactivity and metanephrine excess in the nucleus accumbens after
      prefrontocortical dopamine depletion.
AB  - Selective dopamine depletion within the medial prefrontal cortex in rats is known
      to enhance dopamine and norepinephrine levels in the nucleus accumbens and to
      induce characteristic behavioral disturbances. The present study was designed to
      determine levels of adrenaline, apart from dopamine and norepinephrine, and
      metabolites in the nucleus accumbens after prefrontocortical dopamine depletion.
      Prefrontocortical dopamine depletion was carried out by injecting 6
      hydroxydopamine, and it was validated through: the emergence of behavioral
      disturbances such as amphetamine-induced stereotypies, spontaneous motor
      hyperactivity, and enhanced "anxiety-like" responses and through postmortem
      quantification of catecholamine levels by using high-performance liquid
      chromatography. The findings indicated that lesioned rats exhibited more oral
      stereotypies after amphetamine, were hyperlocomotive, and showed more pronounced
      anxiety-like behaviors than controls. Following prefrontocortical dopamine
      depletion, postmortem concentrations of dopamine and norepinephrine, along with
      the metabolites 3,4-dihydroxyphenylacetic acid and vanillylmandelic acid, were
      reliably enhanced in the nucleus accumbens as expected, and dopamine turnover was
      decreased. Furthermore the nucleus accumbens contained higher levels of
      adrenaline and its transmethylated metabolite metanephrine. To sum up,
      prefrontocortical dopamine depletion induces motor and emotional disturbances in
      rats and alters the neurochemical profile of the nucleus accumbens, not only
      inducing dopaminergic and noradrenergic hyperactivity but also leading to
      adrenaline and metanephrine excess.

PMID- 11247996
TI  - Dendritic glutamate autoreceptors modulate signal processing in rat mitral cells.
AB  - It has been shown recently that in mitral cells of the rat olfactory bulb, N
      methyl-D-aspartate (NMDA) autoreceptors are activated during mitral cell firing.
      Here we consider in more details the mechanisms of mitral cell self-excitation
      and its physiological relevance. We show that both ionotropic NMDA and non-NMDA
      autoreceptors are activated by glutamate released from primary and secondary
      dendrites. In contrast to non-NMDA autoreceptors, NMDA autoreceptors are almost
      exclusively located on secondary dendrites and their activation generates a large
      and sustained self-excitation. Both intracellularly evoked and miniature NMDA-R
      mediated synaptic potentials are blocked by intracellular bis-(o-aminophenoxy)
      N,N,N',N'-tetraacetic acid (BAPTA) and result from a calcium-dependent release of
      glutamate. Self-excitation can be produced by a single spike, and trains of
      spikes result in frequency facilitation. Thus activation of excitatory
      autoreceptors is a major function of action potentials backpropagating in mitral
      cell dendrites, which results in an immediate positive feedback counteracting
      recurrent inhibition and increasing the signal-to-noise ratio of olfactory
      inputs.

PMID- 11247997
TI  - Spontaneous and stimulus-evoked intrinsic optical signals in primary auditory
      cortex of the cat.
AB  - Spontaneous and tone-evoked changes in light reflectance were recorded from
      primary auditory cortex (A1) of anesthetized cats (barbiturate induction,
      ketamine maintenance). Spontaneous 0.1-Hz oscillations of reflectance of 540- and
      690-nm light were recorded in quiet. Stimulation with tone pips evoked localized
      reflectance decreases at 540 nm in 3/10 cats. The distribution of patches
      "activated" by tones of different frequencies reflected the known tonotopic
      organization of auditory cortex. Stimulus-evoked reflectance changes at 690 nm
      were observed in 9/10 cats but lacked stimulus-dependent topography. In two
      experiments, stimulus-evoked optical signals at 540 nm were compared with
      multiunit responses to the same stimuli recorded at multiple sites. A significant
      correlation (P < 0.05) between magnitude of reflectance decrease and multiunit
      response strength was evident in only one of five stimulus conditions in each
      experiment. There was no significant correlation when data were pooled across all
      stimulus conditions in either experiment. In one experiment, the spatial
      distribution of activated patches, evident in records of spontaneous activity at
      540 nm, was similar to that of patches activated by tonal stimuli. These results
      suggest that local cerebral blood volume changes reflect the gross tonotopic
      organization of A1 but are not restricted to the sites of spiking neurons.

PMID- 11247998
TI  - Propofol anesthesia and cerebral blood flow changes elicited by vibrotactile
      stimulation: a positron emission tomography study.
AB  - We investigated the effects of the general anesthetic agent propofol on cerebral
      structures involved in the processing of vibrotactile information. Using positron
      emission tomography (PET) and the H(2)(15)O bolus technique, we measured regional
      distribution of cerebral blood flow (CBF) in eight healthy human volunteers. They
      were scanned under five different levels of propofol anesthesia. Using a computer
      controlled infusion, the following plasma levels of propofol were targeted: Level
      W (Waking, 0 microg/ml), Level 1 (0.5 microg/ml), Level 2 (1.5 microg/ml), Level
      3 (3.5 microg/ml), and Level R (Recovery). At each level of anesthesia, two 3-min
      scans were acquired with vibrotactile stimulation of the right forearm either on
      or off. The level of consciousness was evaluated before each scan by the response
      of the subject to a verbal command. At Level W, all volunteers were fully awake.
      They reported being slightly drowsy at Level 1, they had a slurred speech and
      slow response at Level 2, and they were not responding at all at Level 3. The
      following variations in regional CBF (rCBF) were observed. During the waking
      state (Level W), vibrotactile stimulation induced a significant rCBF increase in
      the left thalamus and in several cortical regions, including the left primary
      somatosensory cortex and the left and right secondary somatosensory cortex.
      During anesthesia, propofol reduced in a dose-dependent manner rCBF in the
      thalamus as well as in a number of visual, parietal, and prefrontal cortical
      regions. At Level 1 through 3, propofol also suppressed vibration-induced
      increases in rCBF in the primary and secondary somatosensory cortex, whereas the
      thalamic rCBF response was abolished only at Level 3, when volunteers lost
      consciousness. We conclude that propofol interferes with the processing of
      vibrotactile information first at the level of the cortex before attenuating its
      transfer through the thalamus.

PMID- 11247999
TI  - Surface orientation discrimination activates caudal and anterior intraparietal
      sulcus in humans: an event-related fMRI study.
AB  - Perception of surface orientation is an essential step for the reconstruction of
      the three-dimensional (3D) structure of an object. Human lesion and functional
      neuroimaging studies have demonstrated the importance of the parietal lobe in
      this task. In primate single-unit studies, neurons in the caudal part of the
      intraparietal sulcus (CIP) were found to be active during the extraction of
      surface orientation through monocular (two-dimensional) cues such as texture
      gradients and linear perspective as well as binocular (3D) cues such as disparity
      gradient and orientation disparity. We used event-related fMRI to study the
      functional neuroanatomy of surface orientation discrimination using stimuli with
      monocular depth cues in six volunteers. Both posterior (CIP) and anterior (AIP)
      areas within the intraparietal sulcus showed a stronger activation during surface
      orientation as compared with a control (color discrimination) task using
      identical stimuli. Furthermore, the signal changes in CIP showed a greater
      performance effect than those in AIP, suggesting that CIP is tightly linked to
      the discrimination task.

PMID- 11248000
TI  - Representation of pleasant and aversive taste in the human brain.
AB  - In this study, the representation of taste in the orbitofrontal cortex was
      investigated to determine whether or not a pleasant and an aversive taste have
      distinct or overlapping representations in this region. The pleasant stimulus
      used was sweet taste (1 M glucose), and the unpleasant stimulus was salt taste
      (0.1 M NaCl). We used an ON/OFF block design in a 3T fMRI scanner with a
      tasteless solution delivered in the OFF period to control for somatosensory or
      swallowing-related effects. It was found that parts of the orbitofrontal cortex
      were activated (P < 0.005 corrected) by glucose (in 6/7 subjects) and by salt (in
      6/7 subjects). In the group analysis, separate areas of the orbitofrontal cortex
      were found to be activated by pleasant and aversive tastes. The involvement of
      the amygdala in the representation of pleasant as well as aversive tastes was
      also investigated. The amygdala was activated (region of interest analysis, P <
      0.025 corrected) by the pleasant taste of glucose (5/7 subjects) as well as by
      the aversive taste of salt (4/7 subjects). Activation by both stimuli was also
      found in the frontal opercular/insular (primary) taste cortex. We conclude that
      the orbitofrontal cortex is involved in processing tastes that have both positive
      and negative affective valence and that different areas of the orbitofrontal
      cortex may be activated by pleasant and unpleasant tastes. We also conclude that
      the amygdala is activated not only by an affectively unpleasant taste, but also
      by a taste that is affectively pleasant, thus providing evidence that the
      amygdala is involved in effects produced by positively affective as well as by
      negatively affective stimuli.

PMID- 11248001
TI  - Somatosensory input to auditory association cortex in the macaque monkey.
AB  - We investigated the convergence of somatosensory and auditory inputs in within
      subregions of macaque auditory cortex. Laminar current source density and
      multiunit activity profiles were sampled with linear array multielectrodes during
      penetrations of the posterior superior temporal plane in three macaque monkeys.
      At each recording site, auditory responses to binaural clicks, pure tones, and
      band-passed noise, all presented by earphones, were compared with somatosensory
      responses evoked by contralateral median nerve stimulation. Subjects were awake
      but were not required to discriminate the stimuli. Borders between A1 and
      surrounding belt regions were identified by mapping best frequency and stimulus
      preferences and by subsequent histological analysis. Regions immediately
      caudomedial to A1 had robust somatosensory responses co-represented with auditory
      responses. In these regions, both somatosensory and auditory response profiles
      had "feedforward" patterns; initial excitation beginning in Lamina 4 and
      spreading to extragranular laminae. Auditory and somatosensory responses
      displayed a high degree of temporal overlap. Anatomical reconstruction indicated
      that the somatosensory input region includes, but may not be restricted to, the
      caudomedial auditory association cortex. As was earlier reported for this region,
      auditory frequency tuning curves were broad and band-passed noise responses were
      larger than pure tone responses. No somatosensory responses were observed in A1.
      These findings suggest a potential neural substrate for multisensory integration
      at an early stage of auditory cortical processing.

PMID- 11248002
TI  - Feedforward and feedback connections between areas V1 and V2 of the monkey have
      similar rapid conduction velocities.
AB  - It is often assumed that the action of cortical feedback connections is slow and
      modulatory, whereas feedforward connections carry a rapid drive to their target
      neurons. Recent results from our laboratory showed a very rapid effect of
      feedback connections on the visual responses of neurons in lower order areas. We
      wanted to determine whether such a rapid action is mediated by fast conducting
      axons. Using electrical stimulation, we compared the conduction velocities along
      feedforward and feedback axons between areas V1 and V2 of the macaque monkey. We
      conclude that feedback and feedforward connections between V1 and V2 have
      comparable fast conduction velocities (around 3.5 m/s).

PMID- 11248003
TI  - Enhancement of short-term synaptic plasticity by prior environmental stress.
AB  - All chemical synapses can rapidly up- or downregulate the strength of their
      connections to reshape the postsynaptic signal, thereby stressing the
      informational importance of specific neural pathways. It is also true that an
      organism's environment can exert a powerful influence on all aspects of neural
      circuitry. We investigated the effect of a prior high-temperature stress on the
      short-term plasticity of a neuromuscular synapse in the hindleg tibial extensor
      muscle of Locusta migratoria. We found that the prior stress acted to
      precondition the synapse by increasing the upper temperature limit for synaptic
      transmission during a subsequent stressful exposure. As well, preexposure to a
      stressful high-temperature environment increased short-term facilitation of
      excitatory junction potentials concurrent with a decrease in excitatory junction
      potential amplitude and a reduction in its temporal parameters. We conclude that
      a stressful environment can modify synaptic physiological properties resulting in
      an enhancement of short-term plasticity of the synapse.

PMID- 11248004
TI  - Dopaminergic substantia nigra neurons express functional nmda receptors in
      postnatal rats.
AB  - Activation of N-methyl-D-aspartate (NMDA) receptors in the Substantia Nigra zona
      compacta (SNc) may determine the degree of physiological apoptosis during the
      early postnatal period. However, the expression of these receptors during this
      stage of development is uncertain, as a recent study failed to detect responses
      to NMDA in unidentified SNc neurons isolated from 2-wk-old rats. Using
      conventional or perforated-patch whole cell recordings, we examined the presence
      of NMDA-evoked responses in SNc neurons acutely dissociated from P4 to P16 rats,
      applying strict criteria for identification of these neurons as nigrostriatal and
      dopaminergic. The SNc neurons were identified by retrograde labeling after
      striatal injection of Fluoro-Gold; the presence of I(h) current; and the
      inhibition of firing by dopamine (50 microM). NMDA (100 microM, V(hold) = -60 mV)
      evoked inward, APV-sensitive currents (56.4 +/- 8.6 pA) in all tested neurons (n
      = 29). Strong depolarizing responses were observed under current-clamp. These
      results indicate that NMDA receptors play a functional role in SNc neurons during
      the first two postnatal weeks.

PMID- 11248005
TI  - Venom from the platypus, Ornithorhynchus anatinus, induces a calcium-dependent
      current in cultured dorsal root ganglion cells.
AB  - The platypus (Ornithorhynchus anatinus), a uniquely Australian species, is one of
      the few living venomous mammals. Although envenomation of humans by many
      vertebrate and invertebrate species results in pain, this is often not the
      principal symptom of envenomation. However, platypus envenomation results in an
      immediate excruciating pain that develops into a very long-lasting hyperalgesia.
      We have previously shown that the venom contains a C-type natriuretic peptide
      that causes mast cell degranulation, and this probably contributes to the
      development of the painful response. Now we demonstrate that platypus venom has a
      potent action on putative nociceptors. Application of the venom to small to
      medium diameter dorsal root ganglion cells for 10 s resulted in an inward current
      lasting several minutes when the venom was diluted in buffer at pH 6.1 but not at
      pH 7.4. The venom itself has a pH of 6.3. The venom activated a current with a
      linear current-voltage relationship between -100 and -25 mV and with a reversal
      potential of -11 mV. Ion substitution experiments indicate that the current is a
      nonspecific cationic current. The response to the venom was blocked by the
      membrane-permeant Ca(2+)-ATPase inhibitor, thapsigargin, and by the tyrosine- and
      serine-kinase inhibitor, k252a. Thus the response appears to be dependent on
      calcium release from intracellular stores. The identity of the venom component(s)
      that is responsible for the responses we have described is yet to be determined
      but is probably not the C-type natriuretic peptide or the defensin-like peptides
      that are present in the venom.

PMID- 11248006
TI  - Extracellular calcium fluctuations and intracellular potentials in the cortex
      during the slow sleep oscillation.
AB  - During slow wave sleep the main activity of cortical neurons consists of
      synchronous and rhythmic alternations of the membrane potential between
      depolarized and hyperpolarized values. The latter are long-lasting (200-600 ms)
      periods of silence. The mechanisms responsible for this periodical interruption
      of cortical network activity are unknown. Here we report a decrease of
      approximately 20% in the extracellular calcium concentration ([Ca](out))
      progressively taking place in the cortex between the onset and the offset of the
      depolarizing phase of the slow sleep oscillation. Since [Ca](out) exerts a high
      gain modulation of synaptic transmission, we estimated the associated transmitter
      release probability and found a corresponding 50% drop. Thus the periods of
      silence occurring in the cortical network during slow wave sleep are promoted by
      recurrent [Ca](out) depletions.

PMID- 11248007
TI  - Chemoprevention: increased potential to bear fruit.

PMID- 11248008
TI  - Closing down on glyphosate inhibition--with a new structure for drug discovery.

PMID- 11248009
TI  - Calcineurin inhibition and cardiac hypertrophy: a matter of balance.

PMID- 11248011
TI  - Hand morphology, manipulation, and tool use in Neandertals and early modern
      humans of the Near East.

PMID- 11248010
TI  - Right on target: novel approaches for the direct visualization of CD1-specific T
      cell responses.

PMID- 11248012
TI  - The increasingly plastic, hormone-responsive adult brain.

PMID- 11248014
TI  - Using three-dimensional microfluidic networks for solving computationally hard
      problems.
AB  - This paper describes the design of a parallel algorithm that uses moving fluids
      in a three-dimensional microfluidic system to solve a nondeterministically
      polynomial complete problem (the maximal clique problem) in polynomial time. This
      algorithm relies on (i) parallel fabrication of the microfluidic system, (ii)
      parallel searching of all potential solutions by using fluid flow, and (iii)
      parallel optical readout of all solutions. This algorithm was implemented to
      solve the maximal clique problem for a simple graph with six vertices. The
      successful implementation of this algorithm to compute solutions for small-size
      graphs with fluids in microchannels is not useful, per se, but does suggest
      broader application for microfluidics in computation and control.

PMID- 11248013
TI  - Breaking open a protein barrel.

PMID- 11248016
TI  - Logic gates using high Rydberg states.
AB  - Connected logic gates can be operated on the levels of one molecule by making use
      of the special properties of high Rydberg states. Explicit experimental results
      for the NO molecule are provided as an example. A number of other options,
      including that of several gates concatenated so as to operate as a full adder,
      are discussed. Specific properties of high Rydberg states that are used are:
      their autoionization is delayed so that they can be distinguished from direct
      multiphoton ionization, during their long life such states also can decay by
      energy transfer to the molecular core in a way that can be controlled by the
      judicious application of very weak external electrical fields, and the Rydberg
      states can be detected by the application of an ionizing electrical field. The
      combination of two (or three) color photons with and without external weak fields
      allows the construction of quite elaborate logic circuit diagrams and shows that
      taking advantage of the different intramolecular dynamics of levels that differ
      by their excitation enables the compounding of logic operations on one molecular
      frame.

PMID- 11248015
TI  - Global analysis of proteasomal substrate specificity using positional-scanning
      libraries of covalent inhibitors.
AB  - The proteasome is a large protease complex consisting of multiple catalytic
      subunits that function simultaneously to digest protein substrates. This
      complexity has made deciphering the role each subunit plays in the generation of
      specific protein fragments difficult. Positional scanning libraries of peptide
      vinyl sulfones were generated in which the amino acid located directly at the
      site of hydrolysis (P1 residue) was held constant and sequences distal to that
      residue (P2, P3, and P4 positions) were varied across all natural amino acids
      (except cysteine and methionine). Binding information for each of the individual
      catalytic subunits was obtained for each library under a variety of different
      conditions. The resulting specificity profiles indicated that substrate positions
      distal to P1 are critical for directing substrates to active subunits in the
      complex. Furthermore, specificity profiles of IFN-gamma-regulated subunits
      closely matched those of their noninducible counterparts, suggesting that subunit
      swapping may modulate substrate processing by a mechanism that does require a
      change in the primary sequence specificity of individual catalytic subunits in
      the complex. Finally, specificity profiles were used to design specific
      inhibitors of a single active site in the complex. These reagents can be used to
      further establish the role of each subunit in substrate processing by the
      proteasome.

PMID- 11248017
TI  - Behavioral inferences from the Skhul/Qafzeh early modern human hand remains.
AB  - Two groups of humans are found in the Near East approximately 100,000 years ago,
      the late archaic Neanderthals and the early modern Skhul/Qafzeh humans.
      Observations that Neanderthals were more heavily muscled, had stronger upper-limb
      bones, and possessed unusual shapes and orientations of some upper-limb joint
      complexes relative to the Skhul/Qafzeh hominids, have led some researchers to
      conclude that significant between-group upper-limb-related behavioral differences
      must have been present, despite the association of the two groups with similar
      Middle Paleolithic archeological complexes. A three-dimensional morphometric
      analysis of the hand remains of the Skhul/Qafzeh hominids, Neanderthals, early
      and late Upper Paleolithic humans, and Holocene humans supports the dichotomy.
      The Skhul/Qafzeh carpometacarpal remains do not have any unique morphologies
      relative to the other fossil samples remains examined. However, in the
      functionally significant metacarpal 1 and 3 bases they resemble Upper Paleolithic
      humans, not Neanderthals. Furthermore, the Skhul/Qafzeh sample differs
      significantly from the Neanderthals in many other aspects of hand functional
      anatomy. Given the correlations between changes in tool technologies and
      functional adaptations seen in the hands of Upper Paleolithic humans, it is
      concluded that the Skhul/Qafzeh hand remains were adapted to Upper Paleolithic
      like manipulative repertoires. These results support the inference of significant
      behavioral differences between Neanderthals and the Skhul/Qafzeh hominids and
      indicate that a significant shift in human manipulative behaviors was associated
      with the earliest stages of the emergence of modern humans.

PMID- 11248018
TI  - Mapping the early steps in the pH-induced conformational conversion of the prion
      protein.
AB  - Under certain conditions, the prion protein (PrP) undergoes a conformational
      change from the normal cellular isoform, PrP(C), to PrP(Sc), an infectious
      isoform capable of causing neurodegenerative diseases in many mammals. Conversion
      can be triggered by low pH, and in vivo this appears to take place in an
      endocytic pathway and/or caveolae-like domains. It has thus far been impossible
      to characterize the conformational change at high resolution by experimental
      methods. Therefore, to investigate the effect of acidic pH on PrP conformation,
      we have performed 10-ns molecular dynamics simulations of PrP(C) in water at
      neutral and low pH. The core of the protein is well maintained at neutral pH. At
      low pH, however, the protein is more dynamic, and the sheet-like structure
      increases both by lengthening of the native beta-sheet and by addition of a
      portion of the N terminus to widen the sheet by another two strands. The side
      chain of Met-129, a polymorphic codon in humans associated with variant
      Creutzfeldt-Jakob disease, pulls the N terminus into the sheet. Neutralization of
      Asp-178 at low pH removes interactions that inhibit conversion, which is
      consistent with the Asp-178-Asn mutation causing human prion diseases.

PMID- 11248019
TI  - Identification of protein oligomerization states by analysis of interface
      conservation.
AB  - The discrimination of true oligomeric protein-protein contacts from nonspecific
      crystal contacts remains problematic. Criteria that have been used previously
      base the assignment of oligomeric state on consideration of the area of the
      interface and/or the results of scoring functions based on statistical
      potentials. Both techniques have a high success rate but fail in more than 10% of
      cases. More importantly, the oligomeric states of several proteins are
      incorrectly assigned by both methods. Here we test the hypothesis that true
      oligomeric contacts should be identifiable on the basis of an increased degree of
      conservation of the residues involved in the interface. By quantifying the degree
      of conservation of the interface and comparing it with that of the remainder of
      the protein surface, we develop a new criterion that provides a highly effective
      complement to existing methods.

PMID- 11248020
TI  - Structure of a flavin-binding plant photoreceptor domain: insights into light
      mediated signal transduction.
AB  - Phototropin, a major blue-light receptor for phototropism in seed plants,
      exhibits blue-light-dependent autophosphorylation and contains two light, oxygen,
      or voltage (LOV) domains and a serine/threonine kinase domain. The LOV domains
      share homology with the PER-ARNT-SIM (PAS) superfamily, a diverse group of sensor
      proteins. Each LOV domain noncovalently binds a single FMN molecule and exhibits
      reversible photochemistry in vitro when expressed separately or in tandem. We
      have determined the crystal structure of the LOV2 domain from the phototropin
      segment of the chimeric fern photoreceptor phy3 to 2.7-A resolution. The
      structure constitutes an FMN-binding fold that reveals how the flavin cofactor is
      embedded in the protein. The single LOV2 cysteine residue is located 4.2 A from
      flavin atom C(4a), consistent with a model in which absorption of blue light
      induces formation of a covalent cysteinyl-C(4a) adduct. Residues that interact
      with FMN in the phototropin segment of the chimeric fern photoreceptor (phy3)
      LOV2 are conserved in LOV domains from phototropin of other plant species and
      from three proteins involved in the regulation of circadian rhythms in
      Arabidopsis and Neurospora. This conservation suggests that these domains exhibit
      the same overall fold and share a common mechanism for flavin binding and light
      induced signaling.

PMID- 11248021
TI  - Assembly of the neutrophil respiratory burst oxidase: a direct interaction
      between p67PHOX and cytochrome b558.
AB  - Activation of the phagocyte NADPH oxidase complex requires the assembly of the
      cytosolic factors p47(PHOX), p67(PHOX), p40(PHOX), and Rac1 or Rac2, with the
      membrane-bound cytochrome b(558). Whereas the interaction of p47(PHOX) with
      cytochrome b(558) is well established, an interaction between p67(PHOX) and
      cytochrome b(558) has never been investigated. We report here a direct
      interaction between p67(PHOX) and cytochrome b(558). First, labeled p67(PHOX)
      recognizes a 91-kDa band in specific granules from a normal patient but not from
      a cytochrome b(558)-deficient patient. Second, p67(PHOX) binds to cytochrome
      b(558) that has been bound to nitrocellulose. Third, GTP-p67(PHOX) bound to
      glutathione agarose is able to pull down cytochrome b(558.) Rac1-GTP or Rac1-GDP
      increased the binding of p67(PHOX) to cytochrome b(558), suggesting that at least
      one of the oxidase-related functions of Rac1 is to promote the interaction
      between p67(PHOX) and cytochrome b(558).

PMID- 11248022
TI  - Comparing protein-ligand interactions in solution and single crystals by Raman
      spectroscopy.
AB  - By using a Raman microscope, we show that it is possible to probe the
      conformational states in protein crystals and crystal fragments under growth
      conditions (in hanging drops). The flavin cofactor in the enzyme para
      hydroxybenzoate hydroxylase can assume two conformations: buried in the protein
      matrix ("in") or essentially solvent-exposed ("out"). By using Raman difference
      spectroscopy, we previously have identified characteristic flavin marker bands
      for the in and out conformers in the solution phase. Now we show that the flavin
      Raman bands can be used to probe these conformational states in crystals,
      permitting a comparison between solution and crystal environments. The in or out
      marker bands are similar for the respective conformers in the crystal and in
      solution; however, significant differences do exist, showing that the
      environments for the flavin's isoalloxazine ring are not identical in the two
      phases. Moreover, the Raman-band widths of the flavin modes are narrower for both
      in and out conformers in the crystals, indicating that the flavin exists in a
      more limited range of closely related conformational states in the crystal than
      in solution. In general, the ability to compare detailed Raman data for complexes
      in crystals and solution provides a means of bridging crystallographic and
      solution studies.

PMID- 11248023
TI  - Solution structure of the antiapoptotic protein bcl-2.
AB  - The structures of two isoforms of Bcl-2 that differ by two amino acids have been
      determined by NMR spectroscopy. Because wild-type Bcl-2 behaved poorly in
      solution, the structures were determined by using Bcl-2/Bcl-x(L) chimeras in
      which part of the putative unstructured loop of Bcl-2 was replaced with a
      shortened loop from Bcl-x(L). These chimeric proteins have a low pI compared with
      the wild-type protein and are soluble. The structures of the two Bcl-2 isoforms
      consist of 6 alpha-helices with a hydrophobic groove on the surface similar to
      that observed for the homologous protein, Bcl-x(L). Comparison of the Bcl-2
      structures to that of Bcl-x(L) shows that although the overall fold is the same,
      there are differences in the structural topology and electrostatic potential of
      the binding groove. Although the structures of the two isoforms of Bcl-2 are
      virtually identical, differences were observed in the ability of the proteins to
      bind to a 25-residue peptide from the proapoptotic Bad protein and a 16-residue
      peptide from the proapoptotic Bak protein. These results suggest that there are
      subtle differences in the hydrophobic binding groove in Bcl-2 that may translate
      into differences in antiapoptotic activity for the two isoforms.

PMID- 11248025
TI  - An initial ATP-independent step in the unwinding of a herpes simplex virus type I
      origin of replication by a complex of the viral origin-binding protein and single
      strand DNA-binding protein.
AB  - Using a spectrophotometric assay that measures the hyperchromicity that
      accompanies the unwinding of a DNA duplex, we have identified an ATP-independent
      step in the unwinding of a herpes simplex virus type 1 (HSV-1) origin of
      replication, Ori(s), by a complex of the HSV-1 origin binding protein (UL9
      protein) and the HSV-1 single-strand DNA binding protein (ICP8). The sequence
      unwound is the 18-bp A + T-rich segment that links the two high-affinity UL9
      protein binding sites, boxes I and II of Ori(s). P1 nuclease sensitivity of
      Ori(s) and single-strand DNA-dependent ATPase measurements of the UL9 protein
      indicate that, at 37 degrees C, the A + T-rich segment is sufficiently single
      stranded to permit the binding of ICP8. Binding of the UL9 protein to boxes I and
      II then results in the formation of the UL9 protein-ICP8 complex, that can, in
      the absence of ATP, promote unwinding of the A + T-rich segment. On addition of
      ATP, the helicase activity of the UL9 protein-ICP8 complex can unwind boxes I and
      II, permitting access of the replication machinery to the Ori(s) sequences.

PMID- 11248024
TI  - From transforming growth factor-beta signaling to androgen action: identification
      of Smad3 as an androgen receptor coregulator in prostate cancer cells.
AB  - Although transforming growth factor-beta (TGF-beta) has been identified to mainly
      inhibit cell growth, the correlation of elevated TGF-beta with increasing serum
      prostate-specific antigen (PSA) levels in metastatic stages of prostate cancer
      has also been well documented. The molecular mechanism for these two contrasting
      effects of TGF-beta, however, remains unclear. Here we report that Smad3, a
      downstream mediator of the TGF-beta signaling pathway, functions as a coregulator
      to enhance androgen receptor (AR)-mediated transactivation. Compared with the
      wild-type AR, Smad3 acts as a strong coregulator in the presence of 1 nM 5alpha
      dihydrotestosterone, 10 nM 17beta-estradiol, or 1 microM hydroxyflutamide for the
      LNCaP mutant AR (mtAR T877A), found in many prostate tumor patients. We further
      showed that endogenous PSA expression in LNCaP cells can be induced by 5alpha
      dihydrotestosterone, and the addition of the Smad3 further induces PSA
      expression. Together, our findings establish Smad3 as an important coregulator
      for the androgen-signaling pathway and provide a possible explanation for the
      positive role of TGF-beta in androgen-promoted prostate cancer growth.

PMID- 11248026
TI  - Male fertility defects in mice lacking the serine protease inhibitor protease
      nexin-1.
AB  - Understanding infertility and sterility requires knowledge of the molecular
      mechanisms underlying sexual reproduction. We have found that male mice deficient
      for the gene encoding the protease inhibitor protease nexin-1 (PN-1) show a
      marked impairment in fertility from the onset of sexual maturity. Absence of PN-1
      results in altered semen protein composition, which leads to inadequate semen
      coagulation and deficient vaginal plug formation upon copulation. Progressive
      morphological changes of the seminal vesicles also are observed. Consistent with
      these findings, abnormal PN-1 expression was found in the semen of men displaying
      seminal dysfunction. The data demonstrate that the level of extracellular
      proteolytic activity is a critical element in controlling male fertility.

PMID- 11248027
TI  - Identification of two residues in MCM5 critical for the assembly of MCM complexes
      and Stat1-mediated transcription activation in response to IFN-gamma.
AB  - In response to IFN-gamma, the latent cytoplasmic Stat1 (signal transducer and
      activator of transcription) proteins translocate into the nucleus and activate
      transcription. We showed previously that Stat1 recruits a group of nuclear
      proteins, among them MCM5 (minichromosome maintenance) and MCM3, for
      transcription activation. MCM5 directly interacts with the transcription
      activation domain (TAD) of Stat1 and enhances Stat1-mediated transcription
      activation. In this report, we identified two specific residues (R732, K734) in
      MCM5 that are required for the direct interaction between Stat1 and MCM5 both in
      vitro and in vivo. MCM5 containing mutations of R732/K734 did not enhance Stat1
      mediated transcription activation in response to IFN-gamma. In addition, it also
      failed to form complexes with other MCM proteins in vivo, suggesting that these
      two residues may be important for an interaction domain in MCM5. Furthermore,
      MCM5 bearing mutations in its ATPase and helicase domains did not enhance Stat1
      activity. In vitro binding assays indicate that MCM3 does not interact directly
      with Stat1, suggesting that the presence of MCM3 in the group of Stat1TAD
      interacting proteins is due to the association of MCM3 with MCM5. Finally, gel
      filtration analyses of nuclear extracts from INF-gamma-treated cells demonstrate
      that there is a MCM5/3 subcomplex coeluting with Stat1. Together, these results
      strongly suggest that Stat1 recruits a MCM5/3 subcomplex through direct
      interaction with MCM5 in the process of IFN-gamma-induced gene activation.

PMID- 11248028
TI  - Protein factors associated with the SsrA.SmpB tagging and ribosome rescue
      complex.
AB  - SsrA RNA acts as a tRNA and mRNA to modify proteins whose synthesis on ribosomes
      has stalled. Such proteins are marked for degradation by addition of peptide tags
      to their C termini in a reaction mediated by SsrA RNA and SmpB, a specific SsrA
      RNA binding protein. Evidence is presented here for the existence of a larger
      ribonucleoprotein complex that contains ribosomal protein S1, phosphoribosyl
      pyrophosphate synthase, RNase R, and YfbG in addition to SsrA RNA and SmpB.
      Biochemical, genetic, and phylogenetic results suggest potential roles for some
      of these factors in various stages of the ribosome rescue and tagging process
      and/or the presence of functional interactions between one or more of these
      proteins and SsrA.

PMID- 11248029
TI  - Mechanism of topology simplification by type II DNA topoisomerases.
AB  - Type II DNA topoisomerases actively reduce the fractions of knotted and catenated
      circular DNA below thermodynamic equilibrium values. To explain this surprising
      finding, we designed a model in which topoisomerases introduce a sharp bend in
      DNA. Because the enzymes have a specific orientation relative to the bend, they
      act like Maxwell's demon, providing unidirectional strand passage. Quantitative
      analysis of the model by computer simulations proved that it can explain much of
      the experimental data. The required sharp DNA bend was demonstrated by a greatly
      increased cyclization of short DNA fragments from topoisomerase binding and by
      direct visualization with electron microscopy.

PMID- 11248030
TI  - A yeast-like mRNA capping apparatus in Plasmodium falciparum.
AB  - Analysis of the mRNA capping apparatus of the malaria parasite Plasmodium
      falciparum illuminates an evolutionary connection to fungi rather than metazoans.
      We show that P. falciparum encodes separate RNA guanylyltransferase (Pgt1) and
      RNA triphosphatase (Prt1) enzymes and that the triphosphatase component is a
      member of the fungal/viral family of metal-dependent phosphohydrolases, which are
      structurally and mechanistically unrelated to the cysteine-phosphatase-type RNA
      triphosphatases found in metazoans and plants. These results highlight the
      potential for discovery of mechanism-based antimalarial drugs designed to
      specifically block the capping of Plasmodium mRNAs. A simple heuristic scheme of
      eukaryotic phylogeny is suggested based on the structure and physical linkage of
      the triphosphatase and guanylyltransferase enzymes that catalyze cap formation.

PMID- 11248032
TI  - Telomerase inhibitors based on quadruplex ligands selected by a fluorescence
      assay.
AB  - The reactivation of telomerase activity in most cancer cells supports the concept
      that telomerase is a relevant target in oncology, and telomerase inhibitors have
      been proposed as new potential anticancer agents. The telomeric G-rich single
      stranded DNA can adopt in vitro an intramolecular quadruplex structure, which has
      been shown to inhibit telomerase activity. We used a fluorescence assay to
      identify molecules that stabilize G-quadruplexes. Intramolecular folding of an
      oligonucleotide with four repeats of the human telomeric sequence into a G
      quadruplex structure led to fluorescence excitation energy transfer between a
      donor (fluorescein) and an acceptor (tetramethylrhodamine) covalently attached to
      the 5' and 3' ends of the oligonucleotide, respectively. The melting of the G
      quadruplex was monitored in the presence of putative G-quadruplex-binding
      molecules by measuring the fluorescence emission of the donor. A series of
      compounds (pentacyclic crescent-shaped dibenzophenanthroline derivatives) was
      shown to increase the melting temperature of the G-quadruplex by 2-20 degrees C
      at 1 microM dye concentration. This increase in T(m) value was well correlated
      with an increase in the efficiency of telomerase inhibition in vitro. The best
      telomerase inhibitor showed an IC(50) value of 28 nM in a standard telomerase
      repeat amplification protocol assay. Fluorescence energy transfer can thus be
      used to reveal the formation of four-stranded DNA structures, and its
      stabilization by quadruplex-binding agents, in an effort to discover new potent
      telomerase inhibitors.

PMID- 11248031
TI  - RPN4 is a ligand, substrate, and transcriptional regulator of the 26S proteasome:
      a negative feedback circuit.
AB  - The RPN4 (SON1, UFD5) protein of the yeast Saccharomyces cerevisiae is required
      for normal levels of intracellular proteolysis. RPN4 is a transcriptional
      activator of genes encoding proteasomal subunits. Here we show that RPN4 is
      required for normal levels of these subunits. Further, we demonstrate that RPN4
      is extremely short-lived (t(1/2) approximately 2 min), that it directly interacts
      with RPN2, a subunit of the 26S proteasome, and that rpn4Delta cells are
      perturbed in their cell cycle. The degradation signal of RPN4 was mapped to its N
      terminal region, outside the transcription-activation domains of RPN4. The
      ability of RPN4 to augment the synthesis of proteasomal subunits while being
      metabolically unstable yields a negative feedback circuit in which the same
      protein up-regulates the proteasome production and is destroyed by the assembled
      active proteasome.

PMID- 11248033
TI  - Crystal structure of cytochrome P450 14alpha -sterol demethylase (CYP51) from
      Mycobacterium tuberculosis in complex with azole inhibitors.
AB  - Cytochrome P450 14alpha-sterol demethylases (CYP51) are essential enzymes in
      sterol biosynthesis in eukaryotes. CYP51 removes the 14alpha-methyl group from
      sterol precursors such as lanosterol, obtusifoliol, dihydrolanosterol, and 24(28)
      methylene-24,25-dihydrolanosterol. Inhibitors of CYP51 include triazole
      antifungal agents fluconazole and itraconazole, drugs used in treatment of
      topical and systemic mycoses. The 2.1- and 2.2-A crystal structures reported here
      for 4-phenylimidazole- and fluconazole-bound CYP51 from Mycobacterium
      tuberculosis (MTCYP51) are the first structures of an authentic P450 drug target.
      MTCYP51 exhibits the P450 fold with the exception of two striking differences-a
      bent I helix and an open conformation of BC loop-that define an active site
      access channel running along the heme plane perpendicular to the direction
      observed for the substrate entry in P450BM3. Although a channel analogous to that
      in P450BM3 is evident also in MTCYP51, it is not open at the surface. The
      presence of two different channels, with one being open to the surface, suggests
      the possibility of conformationally regulated substrate-in/product-out openings
      in CYP51. Mapping mutations identified in Candida albicans azole-resistant
      isolates indicates that azole resistance in fungi develops in protein regions
      involved in orchestrating passage of CYP51 through different conformational
      stages along the catalytic cycle rather than in residues directly contacting
      fluconazole. These new structures provide a basis for rational design of new,
      more efficacious antifungal agents as well as insight into the molecular
      mechanism of P450 catalysis.

PMID- 11248034
TI  - Mapping the intrinsic curvature and flexibility along the DNA chain.
AB  - The energy of DNA deformation plays a crucial and active role in its packaging
      and its function in the cell. Considerable effort has gone into developing
      methodologies capable of evaluating the local sequence-directed curvature and
      flexibility of a DNA chain. These studies thus far have focused on DNA constructs
      expressly tailored either with anomalous flexibility or curvature tracts. Here we
      demonstrate that these two structural properties can be mapped also along the
      chain of a "natural" DNA with any sequence on the basis of its scanning force
      microscope (SFM) images. To know the orientation of the sequence of the
      investigated DNA molecules in their SFM images, we prepared a palindromic dimer
      of the long DNA molecule under study. The palindromic symmetry also acted as an
      internal gauge of the statistical significance of the analysis carried out on the
      SFM images of the dimer molecules. It was found that although the curvature
      modulus is not efficient in separating static and dynamic contributions to the
      curvature of the population of molecules, the curvature taken with its direction
      (its sign in two dimensions) permits the direct separation of the intrinsic
      curvature from the flexibility contributions. The sequence-dependent flexibility
      seems to vary monotonically with the chain's intrinsic curvature; the chain
      rigidity was found to modulate as its local thermodynamic stability and does not
      correlate with the dinucleotide chain rigidities evaluation made from x-ray data
      by other authors.

PMID- 11248035
TI  - Protein phosphatase 1 regulation by inhibitors and targeting subunits.
AB  - Regulation of protein phosphatase 1 (PP1) by protein inhibitors and targeting
      subunits has been previously studied through the use of recombinant protein
      expressed in Escherichia coli. This preparation is limited by several key
      differences in its properties compared with native PP1. In the present study, we
      have analyzed recombinant PP1 expressed in Sf9 insect cells using baculovirus.
      Sf9 PP1 exhibited properties identical to those of native PP1, with respect to
      regulation by metals, inhibitor proteins, and targeting subunits, and failure to
      dephosphorylate a phosphotyrosine-containing substrate or phospho-DARPP-32
      (Dopamine and cAMP-regulated phosphoprotein, M(r) 32,000). Mutations at Y272 in
      the beta12/beta13 loop resulted in a loss of activity and reduced the sensitivity
      to thiophospho-DARPP-32 and inhibitor-2. Mutations of Y272 also increased the
      relative activity toward a phosphotyrosine-containing substrate or phospho-DARPP
      32. Mutation of acidic groove residues caused no change in sensitivity to
      thiophospho-DARPP-32 or inhibitor-2, but one mutant (E252A:D253A:E256R) exhibited
      an increased K(m) for phosphorylase a. Several PP1/PP2A chimeras were prepared in
      which C-terminal sequences of PP2A were substituted into PP1. Replacement of
      residues 274-330 of PP1 with the corresponding region of PP2A resulted in a large
      loss of sensitivity to thiophospho-DARPP-32 and inhibitor-2, and also resulted in
      a loss of interaction with the targeting subunits, spinophilin and PP1 nuclear
      targeting subunit (PNUTS). More limited alterations in residues in beta12,
      beta13, and beta14 strands highlighted a key role for M290 and C291 in the
      interaction of PP1 with thiophospho-DARPP-32, but not inhibitor-2.

PMID- 11248036
TI  - Herpes simplex virus DNA packaging sequences adopt novel structures that are
      specifically recognized by a component of the cleavage and packaging machinery.
AB  - The product of the herpes simplex virus type 1 U(L)28 gene is essential for
      cleavage of concatemeric viral DNA into genome-length units and packaging of this
      DNA into viral procapsids. To address the role of U(L)28 in this process,
      purified U(L)28 protein was assayed for the ability to recognize conserved
      herpesvirus DNA packaging sequences. We report that DNA fragments containing the
      pac1 DNA packaging motif can be induced by heat treatment to adopt novel DNA
      conformations that migrate faster than the corresponding duplex in nondenaturing
      gels. Surprisingly, these novel DNA structures are high-affinity substrates for
      U(L)28 protein binding, whereas double-stranded DNA of identical sequence
      composition is not recognized by U(L)28 protein. We demonstrate that only one
      strand of the pac1 motif is responsible for the formation of novel DNA structures
      that are bound tightly and specifically by U(L)28 protein. To determine the
      relevance of the observed U(L)28 protein-pac1 interaction to the cleavage and
      packaging process, we have analyzed the binding affinity of U(L)28 protein for
      pac1 mutants previously shown to be deficient in cleavage and packaging in vivo.
      Each of the pac1 mutants exhibited a decrease in DNA binding by U(L)28 protein
      that correlated directly with the reported reduction in cleavage and packaging
      efficiency, thereby supporting a role for the U(L)28 protein-pac1 interaction in
      vivo. These data therefore suggest that the formation of novel DNA structures by
      the pac1 motif confers added specificity on recognition of DNA packaging
      sequences by the U(L)28-encoded component of the herpesvirus cleavage and
      packaging machinery.

PMID- 11248039
TI  - Human fatty acid synthase: role of interdomain in the formation of catalytically
      active synthase dimer.
AB  - The human and animal fatty acid synthases are dimers of two identical
      multifunctional proteins (M(r) 272,000) arranged in an antiparallel
      configuration. This arrangement generates two active centers for fatty acid
      synthesis separated by interdomain (ID) regions and predicts that two appropriate
      halves of the monomer should be able to reconstitute an active fatty acid
      synthesizing center. This prediction was confirmed by the reconstitution of the
      synthase active center by using two heterologously expressed halves of the
      monomer protein. Each of these recombinant halves of synthase monomer contains
      half of the ID regions. We show here that the fatty acid synthase activity could
      not be reconstituted when the ID sequences present in the two recombinant halves
      are deleted, suggesting that these ID sequences are essential for fatty acid
      synthase dimer formation. Further, we confirm that the ID sequences are the only
      regions of fatty acid synthase monomers that showed significant dimer formation,
      by using the yeast two-hybrid system. These results are consistent with the
      proposal that the ID region, which has no known catalytic activity, associates
      readily and holds together the two dynamic active centers of the fatty acid
      synthase dimer, therefore playing an important role in the architecture of
      catalytically active fatty acid synthase.

PMID- 11248037
TI  - Reverse engineering the (beta/alpha )8 barrel fold.
AB  - The (beta/alpha)(8) barrel is the most commonly occurring fold among protein
      catalysts. To lay a groundwork for engineering novel barrel proteins, we
      investigated the amino acid sequence restrictions at 182 structural positions of
      the prototypical (beta/alpha)(8) barrel enzyme triosephosphate isomerase. Using
      combinatorial mutagenesis and functional selection, we find that turn sequences,
      alpha-helix capping and stop motifs, and residues that pack the interface between
      beta-strands and alpha-helices are highly mutable. Conversely, any mutation of
      residues in the central core of the beta-barrel, beta-strand stop motifs, and a
      single buried salt bridge between amino acids R189 and D227 substantially reduces
      catalytic activity. Four positions are effectively immutable: conservative single
      substitutions at these four positions prevent the mutant protein from
      complementing a triosephosphate isomerase knockout in Escherichia coli. At 142 of
      the 182 positions, mutation to at least one amino acid of a seven-letter amino
      acid alphabet produces a triosephosphate isomerase with wild-type activity.
      Consequently, it seems likely that (beta/alpha)(8) barrel structures can be
      encoded with a subset of the 20 amino acids. Such simplification would greatly
      decrease the computational burden of (beta/alpha)(8) barrel design.

PMID- 11248038
TI  - Synechocystis HSP17 is an amphitropic protein that stabilizes heat-stressed
      membranes and binds denatured proteins for subsequent chaperone-mediated
      refolding.
AB  - The small heat shock proteins (sHSPs) are ubiquitous stress proteins proposed to
      act as molecular chaperones to prevent irreversible protein denaturation. We
      characterized the chaperone activity of Synechocystis HSP17 and found that it has
      not only protein-protective activity, but also a previously unrecognized ability
      to stabilize lipid membranes. Like other sHSPs, recombinant Synechocystis HSP17
      formed stable complexes with denatured malate dehydrogenase and served as a
      reservoir for the unfolded substrate, transferring it to the DnaK/DnaJ/GrpE and
      GroEL/ES chaperone network for subsequent refolding. Large unilamellar vesicles
      made of synthetic and cyanobacterial lipids were found to modulate this refolding
      process. Investigation of HSP17-lipid interactions revealed a preference for the
      liquid crystalline phase and resulted in an elevated physical order in model
      lipid membranes. Direct evidence for the participation of HSP17 in the control of
      thylakoid membrane physical state in vivo was gained by examining an hsp17(-)
      deletion mutant compared with the isogenic wild-type hsp17(+) revertant
      Synechocystis cells. We suggest that, together with GroEL, HSP17 behaves as an
      amphitropic protein and plays a dual role. Depending on its membrane or cytosolic
      location, it may function as a "membrane stabilizing factor" as well as a member
      of a multichaperone protein-folding network. Membrane association of sHSPs could
      antagonize the heat-induced hyperfluidization of specific membrane domains and
      thereby serve to preserve structural and functional integrity of biomembranes.

PMID- 11248040
TI  - Altering dimerization specificity by changes in surface electrostatics.
AB  - Arc repressor forms a homodimer in which the subunits intertwine to create a
      single globular domain. To obtain Arc sequences that fold preferentially as
      heterodimers, variants with surface patches of excess positive or negative charge
      were designed. Several but not all oppositely charged sequence pairs showed
      preferential heterodimer formation. In the most successful design pair, alpha
      helix B of one subunit contained glutamic acids at positions 43, 46, 47, 48, and
      50, whereas the other subunit contained lysines or arginines at these positions.
      A continuum electrostatic model captures many features of the experimental
      results and suggests that the most successful designs include elements of both
      positive and negative design.

PMID- 11248041
TI  - Crystal structure of the C-terminal domain of the RAP74 subunit of human
      transcription factor IIF.
AB  - The x-ray structure of a C-terminal fragment of the RAP74 subunit of human
      transcription factor (TF) IIF has been determined at 1.02-A resolution. The
      alpha/beta structure is strikingly similar to the globular domain of linker
      histone H5 and the DNA-binding domain of hepatocyte nuclear factor 3gamma (HNF
      3gamma), making it a winged-helix protein. The surface electrostatic properties
      of this compact domain differ significantly from those of bona fide winged-helix
      transcription factors (HNF-3gamma and RFX1) and from the winged-helix domains
      found within the RAP30 subunit of TFIIF and the beta subunit of TFIIE. RAP74 has
      been shown to interact with the TFIIF-associated C-terminal domain phosphatase
      FCP1, and a putative phosphatase binding site has been identified within the
      RAP74 winged-helix domain.

PMID- 11248042
TI  - Toward a quantum-mechanical description of metal-assisted phosphoryl transfer in
      pyrophosphatase.
AB  - The wealth of kinetic and structural information makes inorganic pyrophosphatases
      (PPases) a good model system to study the details of enzymatic phosphoryl
      transfer. The enzyme accelerates metal-complexed phosphoryl transfer 10(10)-fold:
      but how? Our structures of the yeast PPase product complex at 1.15 A and fluoride
      inhibited complex at 1.9 A visualize the active site in three different states:
      substrate-bound, immediate product bound, and relaxed product bound. These span
      the steps around chemical catalysis and provide strong evidence that a water
      molecule (O(nu)) directly attacks PPi with a pK(a) vastly lowered by coordination
      to two metal ions and D117. They also suggest that a low-barrier hydrogen bond
      (LBHB) forms between D117 and O(nu), in part because of steric crowding by W100
      and N116. Direct visualization of the double bonds on the phosphates appears
      possible. The flexible side chains at the top of the active site absorb the
      motion involved in the reaction, which may help accelerate catalysis. Relaxation
      of the product allows a new nucleophile to be generated and creates symmetry in
      the elementary catalytic steps on the enzyme. We are thus moving closer to
      understanding phosphoryl transfer in PPases at the quantum mechanical level.
      Ultra-high resolution structures can thus tease out overlapping complexes and so
      are as relevant to discussion of enzyme mechanism as structures produced by time
      resolved crystallography.

PMID- 11248043
TI  - Structure of neurolysin reveals a deep channel that limits substrate access.
AB  - The zinc metallopeptidase neurolysin is shown by x-ray crystallography to have
      large structural elements erected over the active site region that allow
      substrate access only through a deep narrow channel. This architecture accounts
      for specialization of this neuropeptidase to small bioactive peptide substrates
      without bulky secondary and tertiary structures. In addition, modeling studies
      indicate that the length of a substrate N-terminal to the site of hydrolysis is
      restricted to approximately 10 residues by the limited size of the active site
      cavity. Some structural elements of neurolysin, including a five-stranded beta
      sheet and the two active site helices, are conserved with other
      metallopeptidases. The connecting loop regions of these elements, however, are
      much extended in neurolysin, and they, together with other open coil elements,
      line the active site cavity. These potentially flexible elements may account for
      the ability of the enzyme to cleave a variety of sequences.

PMID- 11248045
TI  - Point mutations and sequence variability in proteins: redistributions of
      preexisting populations.
AB  - Here we study the effect of point mutations in proteins on the redistributions of
      the conformational substates. We show that regardless of the location of a
      mutation in the protein structure and of its type, the observed movements of the
      backbone recur largely at the same positions in the structures. Despite the
      different interactions that are disrupted and formed by the residue substitution,
      not only are the conformations very similar, but the regions that move are also
      the same, regardless of their sequential or spatial distance from the mutation.
      This observation leads us to conclude that, apart from some extreme cases, the
      details of the interactions are not critically important in determining the
      protein conformation or in specifying which parts of the protein would be more
      prone to take on different local conformations in response to changes in the
      sequence. This finding further illustrates why proteins manifest a robustness
      toward many mutational events. This nonuniform distribution of the conformer
      population is consistently observed in a variety of protein structural types.
      Topology is critically important in determining folding pathways, kinetics,
      building block cutting, and anatomy trees. Here we show that topology is also
      very important in determining which regions of the protein structure will respond
      to sequence changes, regardless of the sequential or spatial location of the
      mutation.

PMID- 11248046
TI  - Dissipative metabolic patterns respond during neutrophil transmembrane signaling.
AB  - Self-organization is a common theme in biology. One mechanism of self
      organization is the creation of chemical patterns by the diffusion of chemical
      reactants and their nonlinear interactions. We have recently observed sustained
      unidirectional traveling chemical redox [NAD(P)H - NAD(P)(+)] waves within living
      polarized neutrophils. The present study shows that an intracellular metabolic
      wave responds to formyl peptide receptor agonists, but not antagonists, by
      splitting into two waves traveling in opposite directions along a cell's long
      axis. Similar effects were noted with other neutrophil-activating substances.
      Moreover, when cells were exposed to an N-formyl-methionyl-leucyl-phenylalanine
      (FMLP) gradient whose source was perpendicular to the cell's long axis, cell
      metabolism was locally perturbed with reorientation of the pattern in a direction
      perpendicular to the initial cellular axis. Thus, extracellular activating
      signals and the signals' spatial cues are translated into distinct intracellular
      dissipative structures.

PMID- 11248044
TI  - NMR structure of the calreticulin P-domain.
AB  - The NMR structure of the rat calreticulin P-domain, comprising residues 189-288,
      CRT(189-288), shows a hairpin fold that involves the entire polypeptide chain,
      has the two chain ends in close spatial proximity, and does not fold back on
      itself. This globally extended structure is stabilized by three antiparallel beta
      sheets, with the beta-strands comprising the residues 189-192 and 276-279, 206
      209 and 262-265, and 223-226 and 248-251, respectively. The hairpin loop of
      residues 227-247 and the two connecting regions between the beta-sheets contain a
      hydrophobic cluster, where each of the three clusters includes two highly
      conserved tryptophyl residues, one from each strand of the hairpin. The three
      beta-sheets and the three hydrophobic clusters form a repeating pattern of
      interactions across the hairpin that reflects the periodicity of the amino acid
      sequence, which consists of three 17-residue repeats followed by three 14-residue
      repeats. Within the global hairpin fold there are two well-ordered subdomains
      comprising the residues 219-258, and 189-209 and 262-284, respectively. These are
      separated by a poorly ordered linker region, so that the relative orientation of
      the two subdomains cannot be precisely described. The structure type observed for
      CRT(189-288) provides an additional basis for functional studies of the abundant
      endoplasmic reticulum chaperone calreticulin.

PMID- 11248047
TI  - Direct observation of the enhancement of noncooperative protein self-assembly by
      macromolecular crowding: indefinite linear self-association of bacterial cell
      division protein FtsZ.
AB  - Recent measurements of sedimentation equilibrium and sedimentation velocity have
      shown that the bacterial cell division protein FtsZ self-associates to form
      indefinitely long rod-like linear aggregates in the presence of GDP and Mg(2+).
      In the present study, the newly developed technique of non-ideal tracer
      sedimentation equilibrium was used to measure the effect of high concentrations
      up to 150 g/liter-of each of two inert "crowder" proteins, cyanmethemoglobin or
      BSA, on the thermodynamic activity and state of association of dilute FtsZ under
      conditions inhibiting (-Mg(2+)) and promoting (+Mg(2+)) FtsZ self-association.
      Analysis of equilibrium gradients of both FtsZ and crowder proteins indicates
      that, under the conditions of the present experiment, FtsZ interacts with each of
      the two crowder proteins essentially entirely via steric repulsion, which may be
      accounted for quantitatively by a simple model in which hemoglobin, albumin, and
      monomeric FtsZ are modeled as effective spherical hard particles, and each
      oligomeric species of FtsZ is modeled as an effective hard spherocylinder. The
      functional dependence of the sedimentation of FtsZ on the concentrations of FtsZ
      and either crowder indicates that, in the presence of high concentrations of
      crowder, both the weight-average degree of FtsZ self-association and the range of
      FtsZ oligomer sizes present in significant abundance are increased substantially.

PMID- 11248048
TI  - p63 identifies keratinocyte stem cells.
AB  - The proliferative compartment of stratified squamous epithelia consists of stem
      and transient amplifying (TA) keratinocytes. Some polypeptides are more abundant
      in putative epidermal stem cells than in TA cells, but no polypeptide confined to
      the stem cells has yet been identified. Here we show that the p63 transcription
      factor, a p53 homologue essential for regenerative proliferation in epithelial
      development, distinguishes human keratinocyte stem cells from their TA progeny.
      Within the cornea, nuclear p63 is expressed by the basal cells of the limbal
      epithelium, but not by TA cells covering the corneal surface. Human keratinocyte
      stem and TA cells when isolated in culture give rise to holoclones and
      paraclones, respectively. We show by clonal analysis that p63 is abundantly
      expressed by epidermal and limbal holoclones, but is undetectable in paraclones.
      TA keratinocytes, immediately after their withdrawal from the stem cell
      compartment (meroclones), have greatly reduced p63, even though they possess very
      appreciable proliferative capacity. Clonal evolution (i.e., generation of TA
      cells from precursor stem cells) is promoted by the sigma isoform of the 14-3-3
      family of proteins. Keratinocytes whose 14-3-3final sigma has been down-regulated
      remain in the stem cell compartment and maintain p63 during serial cultivation.
      The identification of p63 as a keratinocyte stem cell marker will be of practical
      importance for the clinical application of epithelial cultures in cell therapy as
      well as for studies on epithelial tumorigenesis.

PMID- 11248049
TI  - Arp2/3 complex and actin dynamics are required for actin-based mitochondrial
      motility in yeast.
AB  - The Arp2/3 complex is implicated in actin polymerization-driven movement of
      Listeria monocytogenes. Here, we find that Arp2p and Arc15p, two subunits of this
      complex, show tight, actin-independent association with isolated yeast
      mitochondria. Arp2p colocalizes with mitochondria. Consistent with this result,
      we detect Arp2p-dependent formation of actin clouds around mitochondria in intact
      yeast. Cells bearing mutations in ARP2 or ARC15 genes show decreased velocities
      of mitochondrial movement, loss of all directed movement and defects in
      mitochondrial morphology. Finally, we observe a decrease in the velocity and
      extent of mitochondrial movement in yeast in which actin dynamics are reduced but
      actin cytoskeletal structure is intact. These results support the idea that the
      movement of mitochondria in yeast is actin polymerization driven and that this
      movement requires Arp2/3 complex.

PMID- 11248051
TI  - Recombination-mediated lengthening of terminal telomeric repeats requires the
      Sgs1 DNA helicase.
AB  - The Saccharomyces cerevisiae SGS1 gene encodes a RecQ-like DNA helicase, human
      homologues of which are implicated in the genetic instability disorders, Bloom
      syndrome (BS), Rothmund-Thomson syndrome (RTS), and Werner syndrome (WS).
      Telomerase-negative yeast cells can recover from senescence via two
      recombinational telomere elongation pathways. The "type I" pathway generates
      telomeres with large blocks of telomeric and subtelomeric sequences and short
      terminal repeat tracts. The "type II" pathway generates telomeres with extremely
      long heterogeneous terminal repeat tracts, reminiscent of the long telomeres
      observed in telomerase-deficient human tumors and tumor-derived cell lines. Here,
      we report that telomerase-negative (est2) yeast cells lacking SGS1 senesced more
      rapidly, experienced a higher rate of telomere erosion, and were delayed in the
      generation of survivors. The est2 sgs1 survivors that were generated grew poorly,
      arrested in G(2)/M and possessed exclusively type I telomeres, implying that SGS1
      is critical for the type II pathway. The mouse WS gene suppressed the slow growth
      and G(2)/M arrest phenotype of est2 sgs1 survivors, arguing that the telomeric
      function of SGS1 is conserved. Reintroduction of SGS1 into est2 sgs1 survivors
      restored growth rate and extended terminal tracts by approximately 300 bp. Both
      phenotypes were absolutely dependent on Sgs1 helicase activity. Introduction of
      an sgs1 carboxyl-terminal truncation allele with helicase activity restored
      growth rate without extending telomeres in most cases, demonstrating that type II
      telomeres are not necessary for normal growth in the absence of telomerase.

PMID- 11248050
TI  - Activation of Trp3 by inositol 1,4,5-trisphosphate receptors through displacement
      of inhibitory calmodulin from a common binding domain.
AB  - Mammalian homologues of Drosophila Trp form plasma membrane channels that mediate
      Ca(2+) influx in response to activation of phospholipase C and internal Ca(2+)
      store depletion. Previous studies showed that human Trp3 is activated by inositol
      1,4,5-trisphosphate (IP(3)) receptors (IP(3)Rs) and identified interacting
      domains, one on Trp and two on IP(3)R. We now find that Trp3 binds Ca(2+)
      calmodulin (Ca(2+)/CaM) at a site that overlaps with the IP(3)R binding domain.
      Using patch-clamp recordings from inside-out patches, we further show that Trp3
      has a high intrinsic activity that is suppressed by Ca(2+)/CaM under resting
      conditions, and that Trp3 is activated by the following: a Trp-binding peptide
      from IP(3)R that displaces CaM from Trp3, a myosin light chain kinase Ca(2+)/CaM
      binding peptide that prevents CaM from binding to Trp3, and calmidazolium, an
      inactivator of Ca(2+)/CaM. We conclude that inhibition of the inhibitory action
      of CaM is a key step of Trp3 channel activation by IP(3)Rs.

PMID- 11248052
TI  - Raft-partitioning of the ubiquitin ligases Cbl and Nedd4 upon IgE-triggered cell
      signaling.
AB  - The high affinity receptor for IgE, FcepsilonRI on mast cells and basophils plays
      an essential role in immunological defense. Upon multivalent antigen binding,
      FcepsilonRI becomes phoshorylated by the protein-tyrosine kinase Lyn, as a result
      of receptor clustering in lipid rafts. FcepsilonRI has been shown to be
      ubiquitinated. Ubiquitination can lead to degradation by proteasomes, but it can
      also act as a sorting signal to internalize proteins destined to the
      endosomal/lysosomal pathway. We have analyzed whether FcepsilonRI ubiquitination
      takes place within rafts. We report biochemical and imaging evidence in rat
      basoleukemia cells for the presence of ubiquitinated FcepsilonRI in clustered
      rafts upon receptor activation. Moreover, we demonstrated that the ubiquitin
      ligases Cbl and Nedd4 colocalize with FcepsilonRI patches and showed that both
      ligases become associated with lipid rafts after activation of IgE signaling.
      Because Cbl is known to interact with the FcepsilonRI signaling complex,
      ubiquitination is likely to be an important parameter regulating IgE-triggered
      signaling occurring in rafts.

PMID- 11248053
TI  - Delivery of proteins into living cells by reversible membrane permeabilization
      with streptolysin-O.
AB  - The pore-forming toxin streptolysin O (SLO) can be used to reversibly
      permeabilize adherent and nonadherent cells, allowing delivery of molecules with
      up to 100 kDa mass to the cytosol. Using FITC-labeled albumin, 10(5)-10(6)
      molecules were estimated to be entrapped per cell. Repair of toxin lesions
      depended on Ca(2+)-calmodulin and on intact microtubules, but was not sensitive
      to actin disruption or to inhibition of protein synthesis. Resealed cells were
      viable for days and retained the capacity to endocytose and to proliferate. The
      active domains of large clostridial toxins were introduced into three different
      cell lines. The domains were derived from Clostridium difficile B-toxin and
      Clostridium sordelli lethal toxin, which glycosylate small G-proteins, and from
      Clostridium botulinum C2 toxin, which ADP-ribosylates actin. After delivery with
      SLO, all three toxins disrupted the actin cytoskeleton to cause rounding up of
      the cells. Glucosylation assays demonstrated that G-proteins Rho and Ras were
      retained in the permeabilized cells and were modified by the respective toxins.
      Inactivation of these G-proteins resulted in reduced stimulus-dependent granule
      secretion, whereas ADP-ribosylation of actin by the C. botulinum C2-toxin
      resulted in enhanced secretion in cells. The presented method for introducing
      proteins into living cells should find multifaceted application in cell biology.

PMID- 11248054
TI  - Disruption of the FG nucleoporin NUP98 causes selective changes in nuclear pore
      complex stoichiometry and function.
AB  - The NUP98 gene encodes precursor proteins that generate two nucleoplasmically
      oriented nucleoporins, NUP98 and NUP96. By using gene targeting, we have
      selectively disrupted the murine NUP98 protein, leaving intact the expression and
      localization of NUP96. We show that NUP98 is essential for mouse gastrulation, a
      developmental stage that is associated with rapid cell proliferation, but
      dispensable for basal cell growth. NUP98-/- cells had an intact nuclear envelope
      with a normal number of embedded nuclear pore complexes. Typically, NUP98
      deficient cells contained on average approximately 5-fold more cytoplasmic
      annulate lamellae than control cells. We found that a set of cytoplasmically
      oriented nucleoporins, including NUP358, NUP214, NUP88, and p62, assembled
      inefficiently into nuclear pores of NUP98-/- cells. Instead, these nucleoporins
      were prominently associated with the annulate lamellae. By contrast, a group of
      nucleoplasmically oriented nucleoporins, including NUP153, NUP50, NUP96, and
      NUP93, had no affinity for annulate lamellae and assembled normally into nuclear
      pores. Mutant pores were significantly impaired in transport receptor-mediated
      docking of proteins with a nuclear localization signal or M9 import signal and
      showed weak nuclear import of such substrates. In contrast, the ability of mutant
      pores to import ribosomal protein L23a and spliceosome protein U1A appeared
      intact. These observations show that NUP98 disruption selectively impairs
      discrete protein import pathways and support the idea that transport of distinct
      import complexes through the nuclear pore complex is mediated by specific subsets
      of nucleoporins.

PMID- 11248055
TI  - Circularly permuted green fluorescent proteins engineered to sense Ca2+.
AB  - To visualize Ca(2+)-dependent protein-protein interactions in living cells by
      fluorescence readouts, we used a circularly permuted green fluorescent protein
      (cpGFP), in which the amino and carboxyl portions had been interchanged and
      reconnected by a short spacer between the original termini. The cpGFP was fused
      to calmodulin and its target peptide, M13. The chimeric protein, which we have
      named "pericam," was fluorescent and its spectral properties changed reversibly
      with the amount of Ca(2+), probably because of the interaction between calmodulin
      and M13 leading to an alteration of the environment surrounding the chromophore.
      Three types of pericam were obtained by mutating several amino acids adjacent to
      the chromophore. Of these, "flash-pericam" became brighter with Ca(2+), whereas
      "inverse-pericam" dimmed. On the other hand, "ratiometric-pericam" had an
      excitation wavelength changing in a Ca(2+)-dependent manner. All of the pericams
      expressed in HeLa cells were able to monitor free Ca(2+) dynamics, such as Ca(2+)
      oscillations in the cytosol and the nucleus. Ca(2+) imaging using high-speed
      confocal line-scanning microscopy and a flash-pericam allowed to detect the free
      propagation of Ca(2+) ions across the nuclear envelope. Then, free Ca(2+)
      concentrations in the nucleus and mitochondria were simultaneously measured by
      using ratiometric-pericams having appropriate localization signals, revealing
      that extra-mitochondrial Ca(2+) transients caused rapid changes in the
      concentration of mitochondrial Ca(2+). Finally, a "split-pericam" was made by
      deleting the linker in the flash-pericam. The Ca(2+)-dependent interaction
      between calmodulin and M13 in HeLa cells was monitored by the association of the
      two halves of GFP, neither of which was fluorescent by itself.

PMID- 11248056
TI  - A transcriptional corepressor of Stat1 with an essential LXXLL signature motif.
AB  - Interferon (IFN) treatment induces tyrosine phosphorylation and nuclear
      translocation of Stat1 (signal transducer and activator of transcription) to
      activate or repress transcription. We report here that a member of the protein
      inhibitor of activated STAT family, PIASy, is a transcriptional corepressor of
      Stat1. IFN treatment triggers the in vivo interaction of Stat1 with PIASy, which
      represses Stat1-mediated gene activation without blocking the DNA binding
      activity of Stat1. An LXXLL coregulator signature motif located near the NH(2)
      terminus of PIASy, although not involved in the PIASy-Stat1 interaction, is
      required for the transrepression activity of PIASy. Our studies identify PIASy as
      a transcriptional corepressor of Stat1 and suggest that different PIAS proteins
      may repress STAT-mediated gene activation through distinct mechanisms.

PMID- 11248057
TI  - The nucleoporin Nup98 associates with the intranuclear filamentous protein
      network of TPR.
AB  - The Nup98 gene codes for several alternatively spliced protein precursors. Two in
      vitro translated and autoproteolytically cleaved precursors yielded heterodimers
      of Nup98-6kDa peptide and Nup98-Nup96. TPR (translocated promoter region) is a
      protein that forms filamentous structures extending from nuclear pore complexes
      (NPCs) to intranuclear sites. We found that in vitro translated TPR bound to in
      vitro translated Nup98 and, via Nup98, to Nup96. Double-immunofluorescence
      microscopy with antibodies to TPR and Nup98 showed colocalization. In confocal
      sections the nucleolus itself was only weakly stained but there was intensive
      perinucleolar staining. Striking spike-like structures emanated from this
      perinucleolar ring and attenuated into thinner structures as they extended to the
      nuclear periphery. This characteristic staining pattern of the TPR network was
      considerably enhanced when a myc-tagged pyruvate kinase-6kDa fusion protein was
      overexpressed in HeLa cells. Double-immunoelectron microscopy of these cells
      using anti-myc and anti-TPR antibodies and secondary gold-coupled antibodies
      yielded row-like arrangements of gold particles. Taken together, the
      immunolocalization data support previous electron microscopical data, suggesting
      that TPR forms filaments that extend from the NPC to the nucleolus. We discuss
      the possible implications of the association of Nup98 with this intranuclear TPR
      network for an intranuclear phase of transport.

PMID- 11248058
TI  - Tissue-engineered cells producing complex recombinant proteins inhibit ovarian
      cancer in vivo.
AB  - Techniques of tissue engineering and cell and molecular biology were used to
      create a biodegradable scaffold for transfected cells to produce complex
      proteins. Mullerian Inhibiting Substance (MIS) causes regression of Mullerian
      ducts in the mammalian embryo. MIS also causes regression in vitro of ovarian
      tumor cell lines and primary cells from ovarian carcinomas, which derive from
      Mullerian structures. In a strategy to circumvent the complicated purification
      protocols for MIS, Chinese hamster ovary cells transfected with the human MIS
      gene were seeded onto biodegradable polymers of polyglycolic acid fibers and
      secretion of MIS confirmed. The polymer-cell graft was implanted into the right
      ovarian pedicle of severe combined immunodeficient mice. Serum MIS in the mice
      rose to supraphysiologic levels over time. One week after implantation of the
      polymer-cell graft, IGROV-1 human tumors were implanted under the renal capsule
      of the left kidney. Growth of the IGROV-1 tumors was significantly inhibited in
      the animals with a polymer-cell graft of MIS-producing cells, compared with
      controls. This novel MIS delivery system could have broader applications for
      other inhibitory agents not amenable to efficient purification and provides in
      vivo evidence for a role of MIS in the treatment of ovarian cancer.

PMID- 11248059
TI  - Cloning and mitochondrial localization of full-length D-AKAP2, a protein kinase A
      anchoring protein.
AB  - Differential compartmentalization of signaling molecules in cells and tissues is
      being recognized as an important mechanism for regulating the specificity of
      signal transduction pathways. A kinase anchoring proteins (AKAPs) direct the
      subcellular localization of protein kinase A (PKA) by binding to its regulatory
      (R) subunits. Dual specific AKAPs (D-AKAPs) interact with both RI and RII. A 372
      residue fragment of mouse D-AKAP2 with a 40-residue C-terminal PKA binding region
      and a putative regulator of G protein signaling (RGS) domain was previously
      identified by means of a yeast two-hybrid screen. Here, we report the cloning of
      full-length human D-AKAP2 (662 residues) with an additional putative RGS domain,
      and the corresponding mouse protein less the first two exons (617 residues).
      Expression of D-AKAP2 was characterized by using mouse tissue extracts. Full
      length D-AKAP2 from various tissues shows different molecular weights, possibly
      because of alternative splicing or posttranslational modifications. The cloned
      human gene product has a molecular weight similar to one of the prominent mouse
      proteins. In vivo association of D-AKAP2 with PKA in mouse brain was demonstrated
      by using cAMP agarose pull-down assay. Subcellular localization for endogenous
      mouse, rat, and human D-AKAP2 was determined by immunocytochemistry,
      immunohistochemistry, and tissue fractionation. D-AKAP2 from all three species is
      highly enriched in mitochondria. The mitochondrial localization and the presence
      of RGS domains in D-AKAP2 may have important implications for its function in PKA
      and G protein signal transduction.

PMID- 11248061
TI  - A single nucleotide polymorphism in the RAD51 gene modifies cancer risk in BRCA2
      but not BRCA1 carriers.
AB  - BRCA1 and BRCA2 carriers are at increased risk for both breast and ovarian
      cancer, but estimates of lifetime risk vary widely, suggesting their penetrance
      is modified by other genetic and/or environmental factors. The BRCA1 and BRCA2
      proteins function in DNA repair in conjunction with RAD51. A preliminary report
      suggested that a single nucleotide polymorphism in the 5' untranslated region of
      RAD51 (135C/G) increases breast cancer risk in BRCA1 and BRCA2 carriers. To
      investigate this effect we studied 257 female Ashkenazi Jewish carriers of one of
      the common BRCA1 (185delAG, 5382insC) or BRCA2 (6174delT) mutations. Of this
      group, 164 were affected with breast and/or ovarian cancer and 93 were
      unaffected. RAD51 genotyping was performed on all subjects. Among BRCA1 carriers,
      RAD51-135C frequency was similar in healthy and affected women [6.1% (3 of 49)
      and 9.9% (12 of 121), respectively], and RAD-135C did not influence age of cancer
      diagnosis [Hazard ratio (HR) = 1.18 for disease in RAD51-135C heterozygotes, not
      significant]. However, in BRCA2 carriers, RAD51-135C heterozygote frequency in
      affected women was 17.4% (8 of 46) compared with 4.9% (2 of 41) in unaffected
      women (P = 0.07). Survival analysis in BRCA2 carriers showed RAD51-135C increased
      risk of breast and/or ovarian cancer with an HR of 4.0 [95% confidence interval
      1.6-9.8, P = 0.003]. This effect was largely due to increased breast cancer risk
      with an HR of 3.46 (95% confidence interval 1.3-9.2, P = 0.01) for breast cancer
      in BRCA2 carriers who were RAD51-135C heterozygotes. RAD51 status did not affect
      ovarian cancer risk. These results show RAD51-135C is a clinically significant
      modifier of BRCA2 penetrance, specifically in raising breast cancer risk at
      younger ages.

PMID- 11248060
TI  - Predicting crossover generation in DNA shuffling.
AB  - We introduce a quantitative framework for assessing the generation of crossovers
      in DNA shuffling experiments. The approach uses free energy calculations and
      complete sequence information to model the annealing process. Statistics obtained
      for the annealing events then are combined with a reassembly algorithm to infer
      crossover allocation in the reassembled sequences. The fraction of reassembled
      sequences containing zero, one, two, or more crossovers and the probability that
      a given nucleotide position in a reassembled sequence is the site of a crossover
      event are estimated. Comparisons of the predictions against experimental data for
      five example systems demonstrate good agreement despite the fact that no
      adjustable parameters are used. An in silico case study of a set of 12 subtilases
      examines the effect of fragmentation length, annealing temperature, sequence
      identity and number of shuffled sequences on the number, type, and distribution
      of crossovers. A computational verification of crossover aggregation in regions
      of near-perfect sequence identity and the presence of synergistic reassembly in
      family DNA shuffling is obtained.

PMID- 11248062
TI  - Murine cytomegalovirus M78 protein, a G protein-coupled receptor homologue, is a
      constituent of the virion and facilitates accumulation of immediate-early viral
      mRNA.
AB  - The M78 protein of murine cytomegalovirus exhibits sequence features of a G
      protein-coupled receptor. It is synthesized with early kinetics, it becomes
      partially colocalized with Golgi markers, and it is incorporated into viral
      particles. We have constructed a viral substitution mutant, SMsubM78, which lacks
      most of the M78 ORF. The mutant produces a reduced yield in cultured 10.1
      fibroblast and IC21 macrophage cell lines. The defect is multiplicity dependent
      and greater in the macrophage cell line. Consistent with its growth defect in
      cultured cells, the mutant exhibits reduced pathogenicity in mice, generating
      less infectious progeny than wild-type virus in all organs assayed. SMsubM78
      fails to efficiently activate accumulation of the viral m123 immediate-early mRNA
      in infected macrophages. M78 facilitates the accumulation of the immediate-early
      mRNA in cycloheximide-treated cells, arguing that it acts in the absence of de
      novo protein synthesis. We conclude that the M78 G protein-coupled receptor
      homologue is delivered to cells as a constituent of the virion, and it acts to
      facilitate the accumulation of immediate-early mRNA.

PMID- 11248063
TI  - Genetic interactions between ATM and the nonhomologous end-joining factors in
      genomic stability and development.
AB  - DNA ligase IV (Lig4) and the DNA-dependent protein kinase (DNA-PK) function in
      nonhomologous end joining (NHEJ). However, although Lig4 deficiency causes late
      embryonic lethality, deficiency in DNA-PK subunits (Ku70, Ku80, and DNA-PKcs)
      does not. Here we demonstrate that, similar to p53 deficiency, ataxia
      telangiectasia-mutated (ATM) gene deficiency rescues the embryonic lethality and
      neuronal apoptosis, but not impaired lymphocyte development, associated with Lig4
      deficiency. However, in contrast to p53 deficiency, ATM deficiency enhances
      deleterious effects of Lig4 deficiency on growth potential of embryonic
      fibroblasts (MEFs) and genomic instability in both MEFs and cultured progenitor
      lymphocytes, demonstrating significant differences in the interplay of p53 vs.
      ATM with respect to NHEJ. Finally, in dramatic contrast to effects on Lig4
      deficiency, ATM deficiency causes early embryonic lethality in Ku- or DNA-PKcs
      deficient mice, providing evidence for an NHEJ-independent role for the DNA-PK
      holoenzyme.

PMID- 11248064
TI  - Genomic evidence for a complete sexual cycle in Candida albicans.
AB  - Candida albicans is a diploid fungus that has become a medically important
      opportunistic pathogen in immunocompromised individuals. We have sequenced the C.
      albicans genome to 10.4-fold coverage and performed a comparative genomic
      analysis between C. albicans and Saccharomyces cerevisiae with the objective of
      assessing whether Candida possesses a genetic repertoire that could support a
      complete sexual cycle. Analyzing over 500 genes important for sexual
      differentiation in S. cerevisiae, we find many homologues of genes that are
      implicated in the initiation of meiosis, chromosome recombination, and the
      formation of synaptonemal complexes. However, others are striking in their
      absence. C. albicans seems to have homologues of all of the elements of a
      functional pheromone response pathway involved in mating in S. cerevisiae but
      lacks many homologues of S. cerevisiae genes for meiosis. Other meiotic gene
      homologues in organisms ranging from filamentous fungi to Drosophila melanogaster
      and Caenorhabditis elegans were also found in the C. albicans genome, suggesting
      potential alternative mechanisms of genetic exchange.

PMID- 11248065
TI  - ACVR1B (ALK4, activin receptor type 1B) gene mutations in pancreatic carcinoma.
AB  - DPC4 is known to mediate signals initiated by type beta transforming growth
      factor (TGFbeta) as well as by other TGFbeta superfamily ligands such as activin
      and BMP (bone morphogenic proteins), but mutational surveys of such non-TGFbeta
      receptors have been negative to date. Here we describe the gene structure and
      novel somatic mutations of the activin type I receptor, ACVR1B, in pancreatic
      cancer. ACVR1B has not been described previously as a mutated tumor-suppressor
      gene.

PMID- 11248066
TI  - The second STE12 homologue of Cryptococcus neoformans is MATa-specific and plays
      an important role in virulence.
AB  - Cryptococcus neoformans STE12alpha, a homologue of Saccharomyces cerevisiae
      STE12, exists only in MATalpha strains. We identified another STE12 homologue,
      STE12a, which is MATa specific. As in the case with Deltaste12alpha, the mating
      efficiency for Deltaste12a was reduced significantly. The Deltaste12a strains
      surprisingly still mated with Deltaste12alpha strains. In MATalpha strains,
      STE12a functionally complemented STE12alpha for mating efficacy, haploid
      fruiting, and regulation of capsule size in the mouse brain. Furthermore, when
      STE12a was replaced with two copies of STE12alpha, the resulting MATa strain
      produced hyphae on filament agar. STE12a regulates mRNA levels of several genes
      that are important for virulence including CNLAC1 and CAP genes. STE12a also
      modulates enzyme activities of phospholipase and superoxide dismutase.
      Importantly, deletion of STE12a markedly reduced the virulence in mice, as is the
      case with STE12alpha. Brain smears of mice infected with the Deltaste12a strain
      showed yeast cells with a considerable reduction in capsule size compared with
      those infected with STE12a strains. When the disrupted locus of ste12a was
      replaced with a wild-type STE12a gene, both in vivo and in vitro mutant
      phenotypes were reversed. These results suggest that STE12a and STE12alpha have
      similar functions, and that the mating type of the cells influences the alleles
      to exert their biological effects. C. neoformans, thus, is the first fungal
      species that contains a mating-type-specific STE12 homologue in each mating type.
      Our results demonstrate that mating-type-specific genes are not only important
      for saprobic reproduction but also play an important role for survival of the
      organism in host tissue.

PMID- 11248067
TI  - Toward optimized carbohydrate-based anticancer vaccines: epitope clustering,
      carrier structure, and adjuvant all influence antibody responses to Lewis(y)
      conjugates in mice.
AB  - The feasibility of using carbohydrate-based vaccines for the immunotherapy of
      cancer is being actively explored at the present time. Although a number of
      clinical trials have already been conducted with glycoconjugate vaccines, the
      optimal design and composition of the vaccines has yet to be determined. Among
      the candidate antigens being examined is Lewis(y) (Le(y)), a blood group-related
      antigen that is overexpressed on the majority of human carcinomas. Using Le(y) as
      a model for specificity, we have examined the role of epitope clustering, carrier
      structure, and adjuvant on the immunogenicity of Le(y) conjugates in mice. A
      glycolipopeptide containing a cluster of three contiguous Le(y)-serine epitopes
      and the Pam(3)Cys immunostimulating moiety was found to be superior to a similar
      construct containing only one Le(y)-serine epitope in eliciting antitumor cell
      antibodies. Because only IgM antibodies were produced by this vaccine, the effect
      on immunogenicity of coupling the glycopeptide to keyhole limpet hemocyanin was
      examined; although both IgM and IgG antibodies were formed, the antibodies
      reacted only with the immunizing structure. Reexamination of the clustered Le(y)
      serine Pam(3)Cys conjugate with the adjuvant QS-21 resulted in the identification
      of both IgG and IgM antibodies reacting with tumor cells, thus demonstrating the
      feasibility of an entirely synthetic carbohydrate-based anticancer vaccine in an
      animal model.

PMID- 11248068
TI  - Immunization of metastatic breast cancer patients with a fully synthetic globo H
      conjugate: a phase I trial.
AB  - The carbohydrate antigen globo H commonly found on breast cancer cells is a
      potential target for vaccine therapy. The objectives of this trial were to
      determine the toxicity and immunogenicity of three synthetic globo H-keyhole
      limpet hemocyanin conjugates plus the immunologic adjuvant QS-21. Twenty-seven
      metastatic breast cancer patients received five vaccinations each. The vaccine
      was well tolerated, and no definite differences were observed among the three
      formulations. Serologic analyses demonstrated the generation of IgM antibody
      titers in most patients, with minimal IgG antibody stimulation. There was
      significant binding of IgM antibodies to MCF-7 tumor cells in 16 patients,
      whereas IgG antibody reactivity was observed in a few patients. There was
      evidence of complement-dependent cytotoxicity in several patients. Affinity
      column purification supported the specificity of IgM antibodies for globo H. On
      the basis of these data, globo H will constitute one component of a polyvalent
      vaccine for evaluation in high-risk breast cancer patients.

PMID- 11248069
TI  - Indirect recognition of allopeptides promotes the development of cardiac
      allograft vasculopathy.
AB  - Graft loss from chronic rejection has become the major obstacle to the long-term
      success of whole organ transplantation. In cardiac allografts, chronic rejection
      is manifested as a diffuse and accelerated form of arteriosclerosis, termed
      cardiac allograft vasculopathy. It has been suggested that T-cell recognition of
      processed alloantigens (allopeptides) presented by recipient antigen-presenting
      cells through the indirect pathway of allorecognition plays a critical role in
      the development and progression of chronic rejection. However, definitive
      preclinical evidence to support this hypothesis is lacking. To examine the role
      of indirect allorecognition in a clinically relevant large animal model of
      cardiac allograft vasculopathy, we immunized MHC inbred miniature swine with
      synthetic polymorphic peptides spanning the alpha(1) domain of an allogeneic
      donor-derived swine leukocyte antigen class I gene. Pigs immunized with swine
      leukocyte antigen class I allopeptides showed in vitro proliferative responses
      and in vivo delayed-type hypersensitivity responses to the allogeneic peptides.
      Donor MHC class I disparate hearts transplanted into peptide-immunized
      cyclosporine-treated pigs not only rejected faster than unimmunized cyclosporine
      treated controls (mean survival time = 5.5 +/-1.7 vs. 54.7 +/-3.8 days, P <
      0.001), but they also developed obstructive fibroproliferative coronary artery
      lesions much earlier than unimmunized controls (<9 vs. >30 days). These results
      definitively link indirect allorecognition and cardiac allograft vasculopathy.

PMID- 11248070
TI  - Identification of proacrosin binding protein sp32 precursor as a human
      cancer/testis antigen.
AB  - Serological expression cloning of antigens eliciting a humoral immune response to
      a syngeneic mouse sarcoma identified pem (mouse placenta and embryonic expression
      gene) as a new member of the cancer/testis family. To identify the human
      homologue of pem, mouse pem sequences and pem-related expressed sequence tags
      from human testis were used as PCR primers for amplification using human testis
      cDNA. However, rather than pem, another gene, designated OY-TES-1, was isolated
      and found to be the human homologue of proacrosin binding protein sp32 precursor
      originally identified in mouse, guinea pig, and pig. OY-TES-1 maps to chromosome
      12p12-p13 and contains 10 exons. Southern blot analysis suggests the presence of
      two OY-TES-1-related genes in the human genome. In normal tissues, OY-TES-1 mRNA
      was expressed only in testis, whereas in malignant tissues, a variable proportion
      of a wide array of cancers, including bladder, breast, lung, liver, and colon
      cancers, expressed OY-TES-1. Serological survey of 362 cancer patients with a
      range of different cancers showed antibody to OY-TES-1 in 25 patients. No OY-TES
      1 sera reactivity was found in 20 normal individuals. These findings indicate
      that OY-TES-1 is an additional member of the cancer/testis family of antigens and
      that OY-TES-1 is immunogenic in humans.

PMID- 11248071
TI  - Ligand-independent assembly of recombinant human CD1 by using oxidative refolding
      chromatography.
AB  - CD1 is an MHC class I-like antigen-presenting molecule consisting of a heavy
      chain and beta(2)-microglobulin light chain. The in vitro refolding of synthetic
      MHC class I molecules has always required the presence of ligand. We report here
      the use of a folding method using an immobilized chaperone fragment, a protein
      disulphide isomerase, and a peptidyl-prolyl cis-trans isomerase (oxidative
      refolding chromatography) for the fast and efficient assembly of ligand-free and
      ligand-associated CD1a and CD1b, starting with material synthesized in
      Escherichia coli. The results suggest that "empty" MHC class I-like molecules can
      assemble and remain stable at physiological temperatures in the absence of
      ligand. The use of oxidative refolding chromatography thus is extended to
      encompass complex multisubunit proteins and specifically to members of the
      extensive, functionally diverse and important immunoglobulin supergene family of
      proteins, including those for which a ligand has yet to be identified.

PMID- 11248072
TI  - Human CD1d-glycolipid tetramers generated by in vitro oxidative refolding
      chromatography.
AB  - CD1 molecules are specialized in presenting lipids to T lymphocytes, but
      identification and isolation of CD1-restricted lipid specific T cells has been
      hampered by the lack of reliable and sensitive techniques. We here report the
      construction of CD1d-glycolipid tetramers from fully denatured human CD1d
      molecules by using the technique of oxidative refolding chromatography. We
      demonstrate that chaperone- and foldase-assisted refolding of denatured CD1d
      molecules and beta(2)-microglobulin in the presence of synthetic lipids is a
      rapid method for the generation of functional and specific CD1d tetramers, which
      unlike previously published protocols ensures isolation of CD1d tetramers loaded
      with a single lipid species. The use of human CD1d-alpha-galactosylceramide
      tetramers for ex vivo staining of peripheral blood lymphocytes and intrahepatic T
      cells from patients with viral liver cirrhosis allowed for the first time
      simultaneous analysis of frequency and specificity of natural killer T cells in
      human clinical samples. Application of this protocol to other members of the CD1
      family will provide powerful tools to investigate lipid-specific T cell immune
      responses in health and in disease.

PMID- 11248073
TI  - Intralymphatic immunization enhances DNA vaccination.
AB  - Although DNA vaccines have been shown to elicit potent immune responses in animal
      models, initial clinical trials in humans have been disappointing, highlighting a
      need to optimize their immunogenicity. Naked DNA vaccines are usually
      administered either i.m. or intradermally. The current study shows that
      immunization with naked DNA by direct injection into a peripheral lymph node
      enhances immunogenicity by 100- to 1,000-fold, inducing strong and biologically
      relevant CD8(+) cytotoxic T lymphocyte responses. Because injection directly into
      a lymph node is a rapid and easy procedure in humans, these results have
      important clinical implications for DNA vaccination.

PMID- 11248074
TI  - Site-specific mutations in the mature form of human IL-18 with enhanced
      biological activity and decreased neutralization by IL-18 binding protein.
AB  - IL-18 can be considered a proinflammatory cytokine mediating disease as well as
      an immunostimulatory cytokine that is important for host defense against
      infection and cancer. The high-affinity, constitutively expressed, and
      circulating IL-18 binding protein (IL-18BP), which competes with cell surface
      receptors for IL-18 and neutralizes IL-18 activity, may act as a natural
      antiinflammatory as well as immunosuppressive molecule. In the present studies,
      the IL-18 precursor caspase-1 cleavage site was changed to a factor Xa site, and,
      after expression in Escherichia coli, mature IL-18 was generated by factor Xa
      cleavage. Mature IL-18 generated by factor Xa cleavage was fully active. Single
      point mutations in the mature IL-18 peptide were made, and the biological
      activities of the wild-type (WT) IL-18 were compared with those of the mutants.
      Mutants E42A and K89A exhibited 2-fold increased activity compared with WT IL-18.
      A double mutant, E42A plus K89A, exhibited 4-fold greater activity. Unexpectedly,
      IL-18BP failed to neutralize the double mutant E42A plus K89A compared with WT IL
      18. The K89A mutant was intermediate in being neutralized by IL-18BP, whereas
      neutralization of the E42A mutant was comparable to that in the WT IL-18. The
      identification of E42 and K89 in the mature IL-18 peptide is consistent with
      previous modeling studies of IL-18 binding to IL-18BP and explains the unusually
      high affinity of IL-18BP for IL-18.

PMID- 11248075
TI  - Peyer's patches are required for oral tolerance to proteins.
AB  - To clarify the role of Peyer's patches in oral tolerance induction, BALB/c mice
      were treated in utero with lymphotoxin beta-receptor Ig fusion protein to
      generate mice lacking Peyer's patches. When these Peyer's patch-null mice were
      fed 25 mg of ovalbumin (OVA) before systemic immunization, OVA-specific IgG Ab
      responses in serum and spleen were seen, in marked contrast to low responses in
      OVA-fed normal mice. Further, high T-cell-proliferative- and delayed-type
      hypersensitivity responses were seen in Peyer's patch-null mice given oral OVA
      before systemic challenge. Higher levels of CD4(+) T-cell-derived IFN-gamma, IL
      4, IL-5, and IL-10 syntheses were noted in Peyer's patch-null mice fed OVA,
      whereas OVA-fed normal mice had suppressed cytokine levels. In contrast, oral
      administration of trinitrobenzene sulfonic acid (TNBS) to Peyer's patch-null mice
      resulted in reduced TNBS-specific serum Abs and splenic B cell antitrinitrophenyl
      Ab-forming cell responses after skin painting with picryl chloride. Further, when
      delayed-type hypersensitivity and splenic T cell proliferative responses were
      examined, Peyer's patch-null mice fed TNBS were unresponsive to hapten. Peyer's
      patch-null mice fed trinitrophenyl-OVA failed to induce systemic unresponsiveness
      to hapten or protein. These findings show that organized Peyer's patches are
      required for oral tolerance to proteins, whereas haptens elicit systemic
      unresponsiveness via the intestinal epithelial cell barrier.

PMID- 11248076
TI  - Testicular FasL is expressed by sperm cells.
AB  - The testis is the main source of Fas ligand (FasL) mRNA in rodents; it is
      generally believed that this molecule, expressed on bordering somatic Sertoli
      cells, bestows an immune-privileged status in the testis by eliminating
      infiltrating inflammatory Fas-bearing leukocytes. Our results demonstrate that
      the attribution of testicular expression of FasL to Sertoli cells is erroneous
      and that FasL transcription instead occurs in meiotic and postmeiotic germ cells,
      whereas the protein is only displayed on mature spermatozoa. These findings point
      to a significant role of the Fas system in the biology of mammalian reproduction.

PMID- 11248077
TI  - Targeted inhibition of calcineurin attenuates cardiac hypertrophy in vivo.
AB  - The Ca(2+)-calmodulin-activated Ser/Thr protein phosphatase calcineurin and the
      downstream transcriptional effectors of calcineurin, nuclear factor of activated
      T cells, have been implicated in the hypertrophic response of the myocardium.
      Recently, the calcineurin inhibitory agents cyclosporine A and FK506 have been
      extensively used to evaluate the importance of this signaling pathway in rodent
      models of cardiac hypertrophy. However, pharmacologic approaches have rendered
      equivocal results necessitating more specific or genetic-based inhibitory
      strategies. In this regard, we have generated Tg mice expressing the calcineurin
      inhibitory domains of Cain/Cabin-1 and A-kinase anchoring protein 79 specifically
      in the heart. DeltaCain and DeltaA-kinase-anchoring protein Tg mice demonstrated
      reduced cardiac calcineurin activity and reduced hypertrophy in response to
      catecholamine infusion or pressure overload. In a second approach, adenoviral
      mediated gene transfer of DeltaCain was performed in the adult rat myocardium to
      evaluate the effectiveness of an acute intervention and any potential species
      dependency. DeltaCain adenoviral gene transfer inhibited cardiac calcineurin
      activity and reduced hypertrophy in response to pressure overload without
      reducing aortic pressure. These results provide genetic evidence implicating
      calcineurin as an important mediator of the cardiac hypertrophic response in
      vivo.

PMID- 11248078
TI  - Myocyte-enriched calcineurin-interacting protein, MCIP1, inhibits cardiac
      hypertrophy in vivo.
AB  - Signaling events controlled by calcineurin promote cardiac hypertrophy, but the
      degree to which such pathways are required to transduce the effects of various
      hypertrophic stimuli remains uncertain. In particular, the administration of
      immunosuppressive drugs that inhibit calcineurin has inconsistent effects in
      blocking cardiac hypertrophy in various animal models. As an alternative approach
      to inhibiting calcineurin in the hearts of intact animals, transgenic mice were
      engineered to overexpress a human cDNA encoding the calcineurin-binding protein,
      myocyte-enriched calcineurin-interacting protein-1 (hMCIP1) under control of the
      cardiac-specific, alpha-myosin heavy chain promoter (alpha-MHC). In unstressed
      mice, forced expression of hMCIP1 resulted in a 5-10% decline in cardiac mass
      relative to wild-type littermates, but otherwise produced no apparent structural
      or functional abnormalities. However, cardiac-specific expression of hMCIP1
      inhibited cardiac hypertrophy, reinduction of fetal gene expression, and
      progression to dilated cardiomyopathy that otherwise result from expression of a
      constitutively active form of calcineurin. Expression of the hMCIP1 transgene
      also inhibited hypertrophic responses to beta-adrenergic receptor stimulation or
      exercise training. These results demonstrate that levels of hMCIP1 producing no
      apparent deleterious effects in cells of the normal heart are sufficient to
      inhibit several forms of cardiac hypertrophy, and suggest an important role for
      calcineurin signaling in diverse forms of cardiac hypertrophy. The future
      development of measures to increase expression or activity of MCIP proteins
      selectively within the heart may have clinical value for prevention of heart
      failure.

PMID- 11248079
TI  - Declining brain activity in cognitively normal apolipoprotein E epsilon 4
      heterozygotes: A foundation for using positron emission tomography to efficiently
      test treatments to prevent Alzheimer's disease.
AB  - Cross-sectional positron emission tomography (PET) studies find that cognitively
      normal carriers of the apolipoprotein E (APOE) epsilon4 allele, a common
      Alzheimer's susceptibility gene, have abnormally low measurements of the cerebral
      metabolic rate for glucose (CMRgl) in the same regions as patients with
      Alzheimer's dementia. In this article, we characterize longitudinal CMRgl
      declines in cognitively normal epsilon4 heterozygotes, estimate the power of PET
      to test the efficacy of treatments to attenuate these declines in 2 years, and
      consider how this paradigm could be used to efficiently test the potential of
      candidate therapies for the prevention of Alzheimer's disease. We studied 10
      cognitively normal epsilon4 heterozygotes and 15 epsilon4 noncarriers 50-63 years
      of age with a reported family history of Alzheimer's dementia before and after an
      interval of approximately 2 years. The epsilon4 heterozygotes had significant
      CMRgl declines in the vicinity of temporal, posterior cingulate, and prefrontal
      cortex, basal forebrain, parahippocampal gyrus, and thalamus, and these declines
      were significantly greater than those in the epsilon4 noncarriers. In testing
      candidate primary prevention therapies, we estimate that between 50 and 115
      cognitively normal epsilon4 heterozygotes are needed per active and placebo
      treatment group to detect a 25% attenuation in these CMRgl declines with 80%
      power and P = 0.005 in 2 years. Assuming these CMRgl declines are related to the
      predisposition to Alzheimer's dementia, this study provides a paradigm for
      testing the potential of treatments to prevent the disorder without having to
      study thousands of research subjects or wait many years to determine whether or
      when treated individuals develop symptoms.

PMID- 11248080
TI  - The pattern of gene expression in human CD15+ myeloid progenitor cells.
AB  - We performed a genome-wide analysis of gene expression in primary human CD15(+)
      myeloid progenitor cells. By using the serial analysis of gene expression (SAGE)
      technique, we obtained quantitative information for the expression of 37,519
      unique SAGE-tag sequences. Of these unique tags, (i) 25% were detected at high
      and intermediate levels, whereas 75% were present as single copies, (ii) 53% of
      the tags matched known expressed sequences, 34% of which were matched to more
      than one known expressed sequence, and (iii) 47% of the tags had no matches and
      represent potentially novel genes. The correct genes were confirmed by
      application of the generation of longer cDNA fragments from SAGE tags for gene
      identification (GLGI) technique for high-copy tags with multiple matches. A set
      of genes known to be important in myeloid differentiation were expressed at
      various levels and used different spliced forms. This study provides a normal
      baseline for comparison of gene expression in myeloid diseases. The strategy of
      using SAGE and GLGI techniques in this study has broad applications to the genome
      wide identification of expressed genes.

PMID- 11248081
TI  - FHIT gene therapy prevents tumor development in Fhit-deficient mice.
AB  - The tumor suppressor gene FHIT spans a common fragile site and is highly
      susceptible to environmental carcinogens. FHIT inactivation and loss of
      expression is found in a large fraction of premaligant and malignant lesions. In
      this study, we were able to inhibit tumor development by oral gene transfer,
      using adenoviral or adenoassociated viral vectors expressing the human FHIT gene,
      in heterozygous Fhit(+/-) knockout mice, that are prone to tumor development
      after carcinogen exposure. We therefore suggest that FHIT gene therapy could be a
      novel clinical approach not only in treatment of early stages of cancer, but also
      in prevention of human cancer.

PMID- 11248082
TI  - Heparin and cancer revisited: mechanistic connections involving platelets, P
      selectin, carcinoma mucins, and tumor metastasis.
AB  - Independent studies indicate that expression of sialylated fucosylated mucins by
      human carcinomas portends a poor prognosis because of enhanced metastatic spread
      of tumor cells, that carcinoma metastasis in mice is facilitated by formation of
      tumor cell complexes with blood platelets, and that metastasis can be attenuated
      by a background of P-selectin deficiency or by treatment with heparin. The
      effects of heparin are not primarily due to its anticoagulant action. Other
      explanations have been suggested but not proven. Here, we bring together all
      these unexplained and seemingly disparate observations, showing that heparin
      treatment attenuates tumor metastasis in mice by inhibiting P-selectin-mediated
      interactions of platelets with carcinoma cell-surface mucin ligands. Selective
      removal of tumor mucin P-selectin ligands, a single heparin dose, or a background
      of P-selectin deficiency each reduces tumor cell-platelet interactions in vitro
      and in vivo. Although each of these maneuvers reduced the in vivo interactions
      for only a few hours, all markedly reduce long-term organ colonization by tumor
      cells. Three-dimensional reconstructions by using volume-rendering software show
      that each situation interferes with formation of the platelet "cloak" around
      tumor cells while permitting an increased interaction of monocytes (macrophage
      precursors) with the malignant cells. Finally, we show that human P-selectin is
      even more sensitive to heparin than mouse P-selectin, giving significant
      inhibition at concentrations that are in the clinically acceptable range. We
      suggest that heparin therapy for metastasis prevention in humans be revisited,
      with these mechanistic paradigms in mind.

PMID- 11248083
TI  - Acceleration of atherogenesis by COX-1-dependent prostanoid formation in low
      density lipoprotein receptor knockout mice.
AB  - The cyclooxygenase (COX) product, prostacyclin (PGI(2)), inhibits platelet
      activation and vascular smooth-muscle cell migration and proliferation.
      Biochemically selective inhibition of COX-2 reduces PGI(2) biosynthesis
      substantially in humans. Because deletion of the PGI(2) receptor accelerates
      atherogenesis in the fat-fed low density lipoprotein receptor knockout mouse, we
      wished to determine whether selective inhibition of COX-2 would accelerate
      atherogenesis in this model. To address this hypothesis, we used dosing with
      nimesulide, which inhibited COX-2 ex vivo, depressed urinary 2,3 dinor 6-keto
      PGF(1alpha) by approximately 60% but had no effect on thromboxane formation by
      platelets, which only express COX-1. By contrast, the isoform nonspecific
      inhibitor, indomethacin, suppressed platelet function and thromboxane formation
      ex vivo and in vivo, coincident with effects on PGI(2) biosynthesis
      indistinguishable from nimesulide. Indomethacin reduced the extent of
      atherosclerosis by 55 +/- 4%, whereas nimesulide failed to increase the rate of
      atherogenesis. Despite their divergent effects on atherogenesis, both drugs
      depressed two indices of systemic inflammation, soluble intracellular adhesion
      molecule-1, and monocyte chemoattractant protein-1 to a similar but incomplete
      degree. Neither drug altered serum lipids and the marked increase in vascular
      expression of COX-2 during atherogenesis. Accelerated progression of
      atherosclerosis is unlikely during chronic intake of specific COX-2 inhibitors.
      Furthermore, evidence that COX-1-derived prostanoids contribute to atherogenesis
      suggests that controlled evaluation of the effects of nonsteroidal anti
      inflammatory drugs and/or aspirin on plaque progression in humans is timely.

PMID- 11248084
TI  - Poly(ADP-ribose) polymerase-1 is required for efficient HIV-1 integration.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1; EC ) is an abundant nuclear enzyme,
      activated by DNA strand breaks to attach up to 200 ADP-ribose groups to nuclear
      proteins. As retroviral infection requires integrase-catalyzed DNA strand breaks,
      we examined infection of pseudotyped HIV type I in fibroblasts from mice with a
      targeted deletion of PARP-1. Viral infection is almost totally abolished in PARP
      1 knockout fibroblasts. This protection from infection reflects prevention of
      viral integration into the host genome. These findings suggest a potential for
      PARP inhibitors in therapy of HIV type I infection.

PMID- 11248085
TI  - The nuclear receptor PXR is a lithocholic acid sensor that protects against liver
      toxicity.
AB  - The pregnane X receptor (PXR) is the molecular target for catatoxic steroids such
      as pregnenolone 16alpha-carbonitrile (PCN), which induce cytochrome P450 3A
      (CYP3A) expression and protect the body from harmful chemicals. In this study, we
      demonstrate that PXR is activated by the toxic bile acid lithocholic acid (LCA)
      and its 3-keto metabolite. Furthermore, we show that PXR regulates the expression
      of genes involved in the biosynthesis, transport, and metabolism of bile acids
      including cholesterol 7alpha-hydroxylase (Cyp7a1) and the Na(+)-independent
      organic anion transporter 2 (Oatp2). Finally, we demonstrate that activation of
      PXR protects against severe liver damage induced by LCA. Based on these data, we
      propose that PXR serves as a physiological sensor of LCA, and coordinately
      regulates gene expression to reduce the concentrations of this toxic bile acid.
      These findings suggest that PXR agonists may prove useful in the treatment of
      human cholestatic liver disease.

PMID- 11248086
TI  - An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic
      bile acids.
AB  - Hepatic hydroxylation is an essential step in the metabolism and excretion of
      bile acids and is necessary to avoid pathologic conditions such as cholestasis
      and liver damage. In this report, we demonstrate that the human xenobiotic
      receptor SXR (steroid and xenobiotic receptor) and its rodent homolog PXR
      (pregnane X receptor) serve as functional bile acid receptors in both cultured
      cells and animals. In particular, the secondary bile acid derivative lithocholic
      acid (LCA) is highly hepatotoxic and, as we show here, a metabolic substrate for
      CYP3A hydroxylation. By using combinations of knockout and transgenic animals, we
      show that activation of SXR/PXR is necessary and sufficient to both induce CYP3A
      enzymes and confer resistance to toxicity by LCA, as well as other xenotoxicants
      such as tribromoethanol and zoxazolamine. Therefore, we establish SXR and PXR as
      bile acid receptors and a role for the xenobiotic response in the detoxification
      of bile acids.

PMID- 11248087
TI  - Telomere dysfunction alters the chemotherapeutic profile of transformed cells.
AB  - Telomerase inhibition has been touted as a novel cancer-selective therapeutic
      goal based on the observation of high telomerase levels in most cancers and the
      importance of telomere maintenance in long-term cellular growth and survival.
      Here, the impact of telomere dysfunction on chemotherapeutic responses was
      assessed in normal and neoplastic cells derived from telomerase RNA null (mTERC(
      /-)) mice. Telomere dysfunction, rather than telomerase per se, was found to be
      the principal determinant governing chemosensitivity specifically to agents that
      induced double-stranded DNA breaks (DSB). Enhanced chemosensitivity in telomere
      dysfunctional cells was linked to therapy-induced fragmentation and
      multichromosomal fusions, whereas telomerase reconstitution restored genomic
      integrity and chemoresistance. Loss of p53 function muted the cytotoxic effects
      of DSB-inducing agents in cells with telomere dysfunction. Together, these
      results point to the combined use of DSB-inducing agents and telomere maintenance
      inhibition as an effective anticancer therapeutic approach particularly in cells
      with intact p53-dependent checkpoint responses.

PMID- 11248088
TI  - Inherited susceptibility to uterine leiomyomas and renal cell cancer.
AB  - Herein we report the clinical, histopathological, and molecular features of a
      cancer syndrome with predisposition to uterine leiomyomas and papillary renal
      cell carcinoma. The studied kindred included 11 family members with uterine
      leiomyomas and two with uterine leiomyosarcoma. Seven individuals had a history
      of cutaneous nodules, two of which were confirmed to be cutaneous leiomyomatosis.
      The four kidney cancer cases occurred in young (33- to 48-year-old) females and
      displayed a unique natural history. All these kidney cancers displayed a distinct
      papillary histology and presented as unilateral solitary lesions that had
      metastasized at the time of diagnosis. Genetic-marker analysis mapped the
      predisposition gene to chromosome 1q. Losses of the normal chromosome 1q were
      observed in tumors that had occurred in the kindred, including a uterine
      leiomyoma. Moreover, the observed histological features were used as a tool to
      diagnose a second kindred displaying the phenotype. We have shown that
      predisposition to uterine leiomyomas and papillary renal cell cancer can be
      inherited dominantly through the hereditary leiomyomatosis and renal cell cancer
      (HLRCC) gene. The HLRCC gene maps to chromosome 1q and is likely to be a tumor
      suppressor. Clinical, histopathological, and molecular tools are now available
      for accurate detection and diagnosis of this cancer syndrome.

PMID- 11248089
TI  - Mullerian Inhibiting Substance lowers testosterone in luteinizing hormone
      stimulated rodents.
AB  - Mullerian Inhibiting Substance (MIS) expression is inversely proportional to the
      serum concentration of testosterone in males after birth and in vitro studies
      have shown that MIS can lower testosterone production by Leydig cells. Also, mice
      overexpressing MIS exhibited Leydig cell hypoplasia and lower levels of serum
      testosterone, but it is not clear whether this is a result of MIS affecting the
      development of Leydig cells or their capacity to produce testosterone. To examine
      the hypothesis that MIS treatment will result in decreased testosterone
      production by mature Leydig cells in vivo, we treated luteinizing hormone (LH)
      stimulated adult male rats and mice with MIS and demonstrated that it can lead to
      a several-fold reduction in testosterone in serum and in testicular extracts.
      There was also a slight decrease in 17-OH-progesterone compared to the more
      significant decrease in testosterone, suggesting that MIS might be regulating the
      lyase activity of cytochrome P450c17 hydroxylase/lyase (Cyp17), but not its
      hydroxylase activity. Northern analysis showed that, in both MIS-treated rats and
      mice, the mRNA for Cyp17, which catalyzes the committed step in androgen
      synthesis, was down-regulated. In rats, the mRNA for cytochrome P450 side-chain
      cleavage (P450scc) was also down-regulated by MIS. This was not observed in mice,
      indicating that there might be species-specific regulation by MIS of the enzymes
      involved in the testosterone biosynthetic pathway. Our results show that MIS can
      be used in vivo to lower testosterone production by mature rodent Leydig cells
      and suggest that MIS-mediated down-regulation of the expression of Cyp17, and
      perhaps P450scc, contributes to that effect.

PMID- 11248090
TI  - Vaccination for protection of retinal ganglion cells against death from glutamate
      cytotoxicity and ocular hypertension: implications for glaucoma.
AB  - Our group recently demonstrated that autoimmune T cells directed against central
      nervous system-associated myelin antigens protect neurons from secondary
      degeneration. We further showed that the synthetic peptide copolymer 1 (Cop-1),
      known to suppress experimental autoimmune encephalomyelitis, can be safely
      substituted for the natural myelin antigen in both passive and active
      immunization for neuroprotection of the injured optic nerve. Here we attempted to
      determine whether similar immunizations are protective from retinal ganglion cell
      loss resulting from a direct biochemical insult caused, for example, by glutamate
      (a major mediator of degeneration in acute and chronic optic nerve insults) and
      in a rat model of ocular hypertension. Passive immunization with T cells reactive
      to myelin basic protein or active immunization with myelin oligodendrocyte
      glycoprotein-derived peptide, although neuroprotective after optic nerve injury,
      was ineffective against glutamate toxicity in mice and rats. In contrast, the
      number of surviving retinal ganglion cells per square millimeter in glutamate
      injected retinas was significantly larger in mice immunized 10 days previously
      with Cop-1 emulsified in complete Freund's adjuvant than in mice injected with
      PBS in the same adjuvant (2,133 +/- 270 and 1,329 +/- 121, respectively, mean +/-
      SEM; P < 0.02). A similar pattern was observed when mice were immunized on the
      day of glutamate injection (1,777 +/- 101 compared with 1,414 +/- 36; P < 0.05),
      but not when they were immunized 48 h later. These findings suggest that
      protection from glutamate toxicity requires reinforcement of the immune system by
      antigens that are different from those associated with myelin. The use of Cop-1
      apparently circumvents this antigen specificity barrier. In the rat ocular
      hypertension model, which simulates glaucoma, immunization with Cop-1
      significantly reduced the retinal ganglion cell loss from 27.8% +/- 6.8% to 4.3%
      +/- 1.6%, without affecting the intraocular pressure. This study may point the
      way to a therapy for glaucoma, a neurodegenerative disease of the optic nerve
      often associated with increased intraocular pressure, as well as for acute and
      chronic degenerative disorders in which glutamate is a prominent participant.

PMID- 11248091
TI  - Potency of Michael reaction acceptors as inducers of enzymes that protect against
      carcinogenesis depends on their reactivity with sulfhydryl groups.
AB  - Induction of phase 2 enzymes and elevations of glutathione are major and
      sufficient strategies for protecting mammals and their cells against the toxic
      and carcinogenic effects of electrophiles and reactive forms of oxygen. Inducers
      belong to nine chemical classes and have few common properties except for their
      ability to modify sulfhydryl groups by oxidation, reduction, or alkylation. Much
      evidence suggests that the cellular "sensor" molecule that recognizes the
      inducers and signals the enhanced transcription of phase 2 genes does so by
      virtue of unique and highly reactive sulfhydryl functions that recognize and
      covalently react with the inducers. Benzylidene-alkanones and -cycloalkanones are
      Michael reaction acceptors whose inducer potency is profoundly increased by the
      presence of ortho- (but not other) hydroxyl substituent(s) on the aromatic
      ring(s). This enhancement correlates with more rapid reactivity of the ortho
      hydroxylated derivatives with model sulfhydryl compounds. Proton NMR spectroscopy
      provides no evidence for increased electrophilicity of the beta-vinyl carbons
      (the presumed site of nucleophilic attack) on the hydroxylated inducers.
      Surprisingly, these ortho-hydroxyl groups display a propensity for extensive
      intermolecular hydrogen bond formation, which may raise the reactivity and
      facilitate addition of mercaptans, thereby raising inducer potencies.

PMID- 11248092
TI  - Sensitivity to carcinogenesis is increased and chemoprotective efficacy of enzyme
      inducers is lost in nrf2 transcription factor-deficient mice.
AB  - Induction of phase 2 enzymes, which neutralize reactive electrophiles and act as
      indirect antioxidants, appears to be an effective means for achieving protection
      against a variety of carcinogens in animals and humans. Transcriptional control
      of the expression of these enzymes is mediated, at least in part, through the
      antioxidant response element (ARE) found in the regulatory regions of their
      genes. The transcription factor Nrf2, which binds to the ARE, appears to be
      essential for the induction of prototypical phase 2 enzymes such as glutathione S
      transferases (GSTs) and NAD(P)H:quinone oxidoreductase (NQO1). Constitutive
      hepatic and gastric activities of GST and NQO1 were reduced by 50-80% in nrf2
      deficient mice compared with wild-type mice. Moreover, the 2- to 5-fold induction
      of these enzymes in wild-type mice by the chemoprotective agent oltipraz, which
      is currently in clinical trials, was almost completely abrogated in the nrf2
      deficient mice. In parallel with the enzymatic changes, nrf2-deficient mice had a
      significantly higher burden of gastric neoplasia after treatment with
      benzo[a]pyrene than did wild-type mice. Oltipraz significantly reduced
      multiplicity of gastric neoplasia in wild-type mice by 55%, but had no effect on
      tumor burden in nrf2-deficient mice. Thus, Nrf2 plays a central role in the
      regulation of constitutive and inducible expression of phase 2 enzymes in vivo
      and dramatically influences susceptibility to carcinogenesis. Moreover, the total
      loss of anticarcinogenic efficacy of oltipraz in the nrf2-disrupted mice
      highlights the prime importance of elevated phase 2 gene expression in
      chemoprotection by this and similar enzyme inducers.

PMID- 11248093
TI  - The dependence receptor DCC (deleted in colorectal cancer) defines an alternative
      mechanism for caspase activation.
AB  - The expression of DCC (deleted in colorectal cancer) is often markedly reduced in
      colorectal and other cancers. However, the rarity of point mutations identified
      in DCC coding sequences and the lack of a tumor predisposition phenotype in DCC
      hemizygous mice have raised questions about its role as a tumor suppressor. DCC
      also mediates axon guidance and functions as a dependence receptor; such
      receptors create cellular states of dependence on their respective ligands by
      inducing apoptosis when unoccupied by ligand. We now show that DCC drives cell
      death independently of both the mitochondria-dependent pathway and the death
      receptor/caspase-8 pathway. Moreover, we demonstrate that DCC interacts with both
      caspase-3 and caspase-9 and drives the activation of caspase-3 through caspase-9
      without a requirement for cytochrome c or Apaf-1. Hence, DCC defines an
      additional pathway for the apoptosome-independent caspase activation.

PMID- 11248095
TI  - Preselective gene therapy for Fabry disease.
AB  - Fabry disease is a lipid storage disorder resulting from mutations in the gene
      encoding the enzyme alpha-galactosidase A (alpha-gal A; EC ). We previously have
      demonstrated long-term alpha-gal A enzyme correction and lipid reduction mediated
      by therapeutic ex vivo transduction and transplantation of hematopoietic cells in
      a mouse model of Fabry disease. We now report marked improvement in the
      efficiency of this gene-therapy approach. For this study we used a novel
      bicistronic retroviral vector that engineers expression of both the therapeutic
      alpha-gal A gene and the human IL-2Ralpha chain (huCD25) gene as a selectable
      marker. Coexpression of huCD25 allowed selective immunoenrichment (preselection)
      of a variety of transduced human and murine cells, resulting in enhanced
      intracellular and secreted alpha-gal A enzyme activities. Of particular
      significance for clinical applicability, mobilized CD34(+) peripheral blood
      hematopoietic stem/progenitor cells from Fabry patients have low-background
      huCD25 expression and could be enriched effectively after ex vivo transduction,
      resulting in increased alpha-gal A activity. We evaluated effects of preselection
      in the mouse model of Fabry disease. Preselection of transduced Fabry mouse bone
      marrow cells elevated the level of multilineage gene-corrected hematopoietic
      cells in the circulation of transplanted animals and improved in vivo enzymatic
      activity levels in plasma and organs for more than 6 months after both primary
      and secondary transplantation. These studies demonstrate the potential of using a
      huCD25-based preselection strategy to enhance the clinical utility of ex vivo
      hematopoietic stem/progenitor cell gene therapy of Fabry disease and other
      disorders.

PMID- 11248094
TI  - Unbalanced expression of the different subunits of elongation factor 1 in
      diabetic skeletal muscle.
AB  - In studies using subtraction cloning to screen for alterations in mRNA expression
      in skeletal muscle from humans with Type 2 diabetes mellitus and control
      subjects, one of the most prominent differences was in the mRNA for elongation
      factor (EF)-1alpha. With Northern blot analysis, EF-1alpha expression was
      enhanced by 2- to 6-fold in both Types 1 and 2 human diabetics. In contrast, no
      changes in expression of EF-1beta or -gamma were noted. We observed similar
      results in animal models of Type 1 diabetes. EF-1alpha expression, but not EF
      1beta or -gamma expression, was also enhanced in streptozotocin-induced diabetic
      rats, and this effect was reversed by insulin treatment. An increased level of EF
      1alpha mRNA was also observed in nonobese diabetic mice. This unbalanced
      regulation of the expression of the different subunits of EF-1 may contribute to
      alterations not only in protein synthesis but also in other cellular events
      observed in the diabetic state.

PMID- 11248096
TI  - A role for intracellular pH in membrane IgM-mediated cell death of human B
      lymphomas.
AB  - We show that anti-IgM-induced cell death in a human B lymphoma cell line, B104,
      is associated with early intracellular acidification and cell shrinkage. In
      contrast, another human B cell lymphoma line, Daudi, less susceptible to B cell
      antigen receptor-mediated cell death, responded to anti-IgM with an early
      increase in intracellular pH (pH(i)). The anti-IgM-induced changes of pH(i) were
      associated with different levels of activation of the Na(+)/H(+) exchanger
      isoform 1 (NHE1) as judged by its phosphorylation status. Prevention of anti-IgM
      induced cell death in B104 cells by the calcineurin phosphatase inhibitor,
      cyclosporin A, abrogated both intracellular acidification and cell shrinkage and
      was associated with an increase in the phosphorylation level of NHE1 within the
      first 60 min of stimulation. This indicates a key role for calcineurin in
      regulating pH(i) and cell viability. The potential role of pH(i) in cell
      viability was confirmed in Daudi cells treated with an Na(+)/H(+) exchanger
      inhibitor 5-(N,N-hexamethylene)amiloride. These observations indicate that the
      outcome of the anti-IgM treatment depends on NHE1-controlled pH(i). We suggest
      that inactivation of the NHE1 in anti-IgM-stimulated cells results in
      intracellular acidification and subsequently triggers or amplifies cell death.

PMID- 11248097
TI  - Patients with Alzheimer's disease have reduced activities in midlife compared
      with healthy control-group members.
AB  - The development of Alzheimer's disease (AD) later in life may be reflective of
      environmental factors operating over the course of a lifetime. Educational and
      occupational attainments have been found to be protective against the development
      of the disease but participation in activities has received little attention. In
      a case-control study, we collected questionnaire data about 26 nonoccupational
      activities from ages 20 to 60. Participants included 193 people with probable or
      possible AD and 358 healthy control-group members. Activity patterns for
      intellectual, passive, and physical activities were classified by using an
      adaptation of a published scale in terms of "diversity" (total number of
      activities), "intensity" (hours per month), and "percentage intensity"
      (percentage of total activity hours devoted to each activity category). The
      control group was more active during midlife than the case group was for all
      three activity categories, even after controlling for age, gender, income
      adequacy, and education. The odds ratio for AD in those performing less than the
      mean value of activities was 3.85 (95% confidence interval: 2.65-5.58, P <
      0.001). The increase in time devoted to intellectual activities from early
      adulthood (20-39) to middle adulthood (40-60) was associated with a significant
      decrease in the probability of membership in the case group. We conclude that
      diversity of activities and intensity of intellectual activities were reduced in
      patients with AD as compared with the control group. These findings may be
      because inactivity is a risk factor for the disease or because inactivity is a
      reflection of very early subclinical effects of the disease, or both.

PMID- 11248098
TI  - Appetite of an epiphyte: quantitative monitoring of bacterial sugar consumption
      in the phyllosphere.
AB  - We report here the construction, characterization, and application of a bacterial
      bioreporter for fructose and sucrose that was designed to monitor the
      availability of these sugars to microbial colonizers of the phyllosphere. Plasmid
      pP(fruB)-gfp[AAV] carries the Escherichia coli fruB promoter upstream from the
      gfp[AAV] allele that codes for an unstable variant of green fluorescent protein
      (GFP). In Erwinia herbicola, this plasmid brings about the accumulation of GFP
      fluorescence in response to both fructose and sucrose. Cells of E. herbicola
      (pP(fruB)-gfp[AAV]) were sprayed onto bean plants, recovered from leaves at
      various time intervals after inoculation, and analyzed individually for GFP
      content by quantitative analysis of digital microscope images. We observed a
      positive correlation between single-cell GFP accumulation and ribosomal content
      as determined by fluorescence in situ hybridization, indicating that foliar
      growth of E. herbicola occurred at the expense of fructose and/or sucrose. One
      hour after inoculation, nearly all bioreporter cells appeared to be actively
      engaged in fructose consumption. This fraction dropped to approximately 11% after
      7 h and to approximately 1% a day after inoculation. This pattern suggests a
      highly heterogeneous availability of fructose to individual E. herbicola cells as
      they colonize the phyllosphere. We estimated that individual cells were exposed
      to local initial fructose abundances ranging from less than 0.15 pg fructose to
      more than 4.6 pg.

PMID- 11248099
TI  - Heterogeneous transcription of an indoleacetic acid biosynthetic gene in Erwinia
      herbicola on plant surfaces.
AB  - We investigated the spatial pattern of expression of ipdC, a plant inducible gene
      involved in indoleacetic acid biosynthesis in Erwinia herbicola, among individual
      cells on plants to gain a better understanding of the role of this phenotype in
      the epiphytic ecology of bacteria and the factors involved in the regulation of
      ipdC. Nonpathogenic E. herbicola strain 299R harboring a transcriptional fusion
      of ipdC to gfp was inoculated onto bean plants, recovered from individual leaves
      48 h after inoculation, and subjected to fluorescence in situ hybridization using
      a 16S rRNA oligonucleotide probe specific to strain 299R. Epifluorescence images
      captured through a rhodamine filter were used to distinguish the
      5carboxytetramethylrhodamine-labeled cells of strain 299R from other leaf
      microflora. Quantification of the green fluorescence intensity of individual
      cells by analysis of digital images revealed that about 65% of the 299R cells
      recovered from bean leaves had higher ipdC expression than in culture.
      Additionally, 10% of the cells exhibited much higher levels of green fluorescence
      than the median fluorescence intensity, indicating that they are more
      heterogeneous with respect to ipdC expression on plants than in culture.
      Examination of 299R cells in situ on leaf surfaces by confocal laser scanning
      microscopy after fluorescence in situ hybridization of cells on leaf samples
      showed that even cells that were in close proximity exhibited dramatically
      different green fluorescence intensities, and thus, were in a physical or
      chemical microenvironment that induced differential expression of ipdC.

PMID- 11248100
TI  - Complete genomic sequence of Pasteurella multocida, Pm70.
AB  - We present here the complete genome sequence of a common avian clone of
      Pasteurella multocida, Pm70. The genome of Pm70 is a single circular chromosome
      2,257,487 base pairs in length and contains 2,014 predicted coding regions, 6
      ribosomal RNA operons, and 57 tRNAs. Genome-scale evolutionary analyses based on
      pairwise comparisons of 1,197 orthologous sequences between P. multocida,
      Haemophilus influenzae, and Escherichia coli suggest that P. multocida and H.
      influenzae diverged approximately 270 million years ago and the gamma subdivision
      of the proteobacteria radiated about 680 million years ago. Two previously
      undescribed open reading frames, accounting for approximately 1% of the genome,
      encode large proteins with homology to the virulence-associated filamentous
      hemagglutinin of Bordetella pertussis. Consistent with the critical role of iron
      in the survival of many microbial pathogens, in silico and whole-genome
      microarray analyses identified more than 50 Pm70 genes with a potential role in
      iron acquisition and metabolism. Overall, the complete genomic sequence and
      preliminary functional analyses provide a foundation for future research into the
      mechanisms of pathogenesis and host specificity of this important multispecies
      pathogen.

PMID- 11248101
TI  - Herpesviruses use bidirectional fast-axonal transport to spread in sensory
      neurons.
AB  - Alpha herpesviruses infect the vertebrate nervous system resulting in either mild
      recurrent lesions in mucosal epithelia or fatal encephalitis. Movement of virions
      within the nervous system is a critical factor in the outcome of infection;
      however, the dynamics of individual virion transport have never been assessed.
      Here we visualized and tracked individual viral capsids as they moved in axons
      away from infected neuronal cell bodies in culture. The observed movement was
      compatible with fast axonal flow mediated by multiple microtubule motors. Capsids
      accumulated at axon terminals, suggesting that spread from infected neurons
      required cell contact.

PMID- 11248102
TI  - The targeting pathway of Escherichia coli presecretory and integral membrane
      proteins is specified by the hydrophobicity of the targeting signal.
AB  - Previous studies have demonstrated that presecretory proteins such as maltose
      binding protein (MBP) and outer membrane protein A (OmpA) are targeted to the
      Escherichia coli inner membrane by the molecular chaperone SecB, but that
      integral membrane proteins are targeted by the signal recognition particle (SRP).
      In vitro studies have suggested that trigger factor binds to a sequence near the
      N terminus of the mature region of OmpA and shunts the protein into the SecB
      pathway by blocking an interaction between SRP and the signal peptide. By
      contrast, we have found that the targeting pathway of a protein under
      physiological conditions is dictated by the composition of its targeting signal.
      Replacement of the MBP or OmpA signal peptide with the first transmembrane
      segment of AcrB abolished the dependence on SecB for transport and rerouted both
      proteins into the SRP targeting pathway. More modest alterations of the MBP
      signal peptide that simply increase its hydrophobicity also promoted SRP binding.
      Furthermore, we obtained evidence that SRP has a low affinity for typical signal
      peptides in vivo. These results imply that different classes of E. coli proteins
      are targeted by distinct pathways because bacterial SRP binds to a more
      restricted range of targeting signals than its eukaryotic counterpart.

PMID- 11248104
TI  - Glutamic acid decarboxylase and glutamate receptor changes during tolerance and
      dependence to benzodiazepines.
AB  - Protracted administration of diazepam elicits tolerance, whereas discontinuation
      of treatment results in signs of dependence. Tolerance to the anticonvulsant
      action of diazepam is present in an early phase (6, 24, and 36 h) but disappears
      in a late phase (72-96 h) of withdrawal. In contrast, signs of dependence such as
      decrease in open-arm entries on an elevated plus-maze and increased
      susceptibility to pentylenetetrazol-induced seizures were apparent 96 h (but not
      12, 24, or 48 h) after diazepam withdrawal. During the first 72 h of withdrawal,
      tolerance is associated with changes in the expression of GABA(A) (gamma
      aminobutyric acid type A) receptor subunits (decrease in gamma(2) and alpha(1);
      increase in alpha(5)) and with an increase of mRNA expression of the most
      abundant form of glutamic acid decarboxylase (GAD), GAD(67). In contrast, dl
      alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor GluR1
      subunit mRNA and cognate protein, which are normal during the early phase of
      diazepam withdrawal, increase by approximately 30% in cortex and hippocampus in
      association with the appearance of signs of dependence 96 h after diazepam
      withdrawal. Immunohistochemical studies of GluR1 subunit expression with gold
      immunolabeling technique reveal that the increase of GluR1 subunit protein is
      localized to layer V pyramidal neurons and their apical dendrites in the cortex,
      and to pyramidal neurons and in their dendritic fields in hippocampus. The
      results suggest an involvement of GABA-mediated processes in the development and
      maintenance of tolerance to diazepam, whereas excitatory amino acid-related
      processes (presumably via AMPA receptors) may be involved in the expression of
      signs of dependence after withdrawal.

PMID- 11248103
TI  - Down-regulation of dendritic spine and glutamic acid decarboxylase 67 expressions
      in the reelin haploinsufficient heterozygous reeler mouse.
AB  - Heterozygous reeler mice (HRM) haploinsufficient for reelin express approximately
      50% of the brain reelin content of wild-type mice, but are phenotypically
      different from both wild-type mice and homozygous reeler mice. They exhibit, (i)
      a down-regulation of glutamic acid decarboxylase 67 (GAD(67))-positive neurons in
      some but not every cortical layer of frontoparietal cortex (FPC), (ii) an
      increase of neuronal packing density and a decrease of cortical thickness because
      of neuropil hypoplasia, (iii) a decrease of dendritic spine expression density on
      basal and apical dendritic branches of motor FPC layer III pyramidal neurons, and
      (iv) a similar decrease in dendritic spines expressed on the basal dendrite
      branches of CA1 pyramidal neurons of the hippocampus. To establish whether the
      defect of GAD(67) down-regulation observed in HRM is responsible for neuropil
      hypoplasia and decreased dendritic spine density, we studied heterozygous GAD(67)
      knockout mice (HG(67)M). These mice exhibited a down-regulation of GAD(67) mRNA
      expression in FPC (about 50%), but they expressed normal amounts of reelin and
      had no neuropil hypoplasia or down-regulation of dendritic spine expression.
      These findings, coupled with electron-microscopic observations that reelin
      colocalizes with integrin receptors on dendritic spines, suggest that reelin may
      be a factor in the dynamic expression of cortical dendritic spines perhaps by
      promoting integrin receptor clustering. These findings are interesting because
      the brain neurochemical and neuroanatomical phenotypic traits exhibited by the
      HRM are in several ways similar to those found in postmortem brains of psychotic
      patients.

PMID- 11248105
TI  - Synaptic and extrasynaptic gamma -aminobutyric acid type A receptor clusters in
      rat hippocampal cultures during development.
AB  - We have simultaneously measured the expression of postsynaptic gamma-aminobutyric
      acid type A (GABA(A)) receptor clusters and of presynaptic boutons in neonatal
      rat hippocampal cultures between days 1 and 30. GABA(A) receptors were labeled
      with antibodies recognizing the extracellular domains of beta2/3 and gamma2
      subunits. Boutons were visualized by activity-dependent uptake of the styryl dye
      FM4-64, or by antibodies against the presynaptic vesicular protein SV2 or the
      GABA-synthesizing enzyme glutamic acid decarboxylase (GAD). GABA(A) receptor
      clusters could be seen in living neurons already 6 h after culturing, much before
      presynaptic markers could be identified in nerve terminals. The densities of
      receptor clusters that contained the beta2/3 subunits were constant between days
      10 and 30 in culture, whereas gamma2 subunit-containing clusters fluctuated and
      reached a maximum on day 20. SV2 and GAD staining could be measured from day 2
      onwards. Clustering of GAD in presynaptic terminals and FM4-64 uptake were
      observed only at day 5 and afterward. SV2 staining and FM4-64 uptake increased in
      parallel between days 5 and 20 and remained constant thereafter. GAD-stained
      boutons were fewer than those labeled with other, less specific, presynaptic
      stains. They reached a maximum on day 20 and fell again toward day 30. Double
      labeling of GABA(A) receptors and of presynaptic boutons in neurons during
      differentiation showed that, even after 30 days in culture, large fractions of
      GABA(A) receptor clusters containing beta2/3 and/or gamma2 subunits remained
      extrasynaptic.

PMID- 11248106
TI  - Neural fate of seen and unseen faces in visuospatial neglect: a combined event
      related functional MRI and event-related potential study.
AB  - To compare neural activity produced by visual events that escape or reach
      conscious awareness, we used event-related MRI and evoked potentials in a patient
      who had neglect and extinction after focal right parietal damage, but intact
      visual fields. This neurological disorder entails a loss of awareness for stimuli
      in the field contralateral to a brain lesion when stimuli are simultaneously
      presented on the ipsilateral side, even though early visual areas may be intact,
      and single contralateral stimuli may still be perceived. Functional MRI and event
      related potential study were performed during a task where faces or shapes
      appeared in the right, left, or both fields. Unilateral stimuli produced normal
      responses in V1 and extrastriate areas. In bilateral events, left faces that were
      not perceived still activated right V1 and inferior temporal cortex and evoked
      nonsignificantly reduced N1 potentials, with preserved face-specific negative
      potentials at 170 ms. When left faces were perceived, the same stimuli produced
      greater activity in a distributed network of areas including right V1 and cuneus,
      bilateral fusiform gyri, and left parietal cortex. Also, effective connectivity
      between visual, parietal, and frontal areas increased during perception of faces.
      These results suggest that activity can occur in V1 and ventral temporal cortex
      without awareness, whereas coupling with dorsal parietal and frontal areas may be
      critical for such activity to afford conscious perception.

PMID- 11248107
TI  - alpha10: a determinant of nicotinic cholinergic receptor function in mammalian
      vestibular and cochlear mechanosensory hair cells.
AB  - We report the cloning and characterization of rat alpha10, a previously
      unidentified member of the nicotinic acetylcholine receptor (nAChR) subunit gene
      family. The protein encoded by the alpha10 nAChR subunit gene is most similar to
      the rat alpha9 nAChR, and both alpha9 and alpha10 subunit genes are transcribed
      in adult rat mechanosensory hair cells. Injection of Xenopus laevis oocytes with
      alpha10 cRNA alone or in pairwise combinations with either alpha2-alpha6 or beta2
      beta4 subunit cRNAs yielded no detectable ACh-gated currents. However,
      coinjection of alpha9 and alpha10 cRNAs resulted in the appearance of an unusual
      nAChR subtype. Compared with homomeric alpha9 channels, the alpha9alpha10 nAChR
      subtype displays faster and more extensive agonist-mediated desensitization, a
      distinct current-voltage relationship, and a biphasic response to changes in
      extracellular Ca(2+) ions. The pharmacological profiles of homomeric alpha9 and
      heteromeric alpha9alpha10 nAChRs are essentially indistinguishable and closely
      resemble those reported for endogenous cholinergic eceptors found in vertebrate
      hair cells. Our data suggest that efferent modulation of hair cell function
      occurs, at least in part, through heteromeric nAChRs assembled from both alpha9
      and alpha10 subunits.

PMID- 11248108
TI  - Plasticity of the cochleotopic (frequency) map in specialized and nonspecialized
      auditory cortices.
AB  - Auditory conditioning (associative learning) causes reorganization of the
      cochleotopic (frequency) maps of the primary auditory cortex (AI) and the
      inferior colliculus. Focal electric stimulation of the AI also evokes basically
      the same cortical and collicular reorganization as that caused by conditioning.
      Therefore, part of the neural mechanism for the plasticity of the central
      auditory system caused by conditioning can be explored by focal electric
      stimulation of the AI. The reorganization is due to shifts in best frequencies
      (BFs) together with shifts in frequency-tuning curves of single neurons. In the
      AI of the Mongolian gerbil (Meriones unguiculatus) and the posterior division of
      the AI of the mustached bat (Pteronotus parnellii), focal electric stimulation
      evokes BF shifts of cortical auditory neurons located within a 0.7-mm distance
      along the frequency axis. The amount and direction of BF shift differ depending
      on the relationship in BF between stimulated and recorded neurons, and between
      the gerbil and mustached bat. Comparison in BF shift between different mammalian
      species and between different cortical areas of a single species indicates that
      BF shift toward the BF of electrically stimulated cortical neurons (centripetal
      BF shift) is common in the AI, whereas BF shift away from the BF of electrically
      stimulated cortical neurons (centrifugal BF shift) is special. Therefore, we
      propose a hypothesis that reorganization, and accordingly organization, of
      cortical auditory areas caused by associative learning can be quite different
      between specialized and nonspecialized (ordinary) areas of the auditory cortex.

PMID- 11248109
TI  - Spontaneous corticospinal axonal plasticity and functional recovery after adult
      central nervous system injury.
AB  - Although it is believed that little recovery occurs after adult mammalian spinal
      cord injury, in fact significant spontaneous functional improvement commonly
      occurs after spinal cord injury in humans. To investigate potential mechanisms
      underlying spontaneous recovery, lesions of defined components of the
      corticospinal motor pathway were made in adult rats in the rostral cervical
      spinal cord or caudal medulla. Following complete lesions of the dorsal
      corticospinal motor pathway, which contains more than 95% of all corticospinal
      axons, spontaneous sprouting from the ventral corticospinal tract occurred onto
      medial motoneuron pools in the cervical spinal cord; this sprouting was
      paralleled by functional recovery. Combined lesions of both dorsal and ventral
      corticospinal tract components eliminated sprouting and functional recovery. In
      addition, functional recovery was also abolished if dorsal corticospinal tract
      lesions were followed 5 weeks later by ventral corticospinal tract lesions. We
      found extensive spontaneous structural plasticity as a mechanism correlating with
      functional recovery in motor systems in the adult central nervous system.
      Experimental enhancement of spontaneous plasticity may be useful to promote
      further recovery after adult central nervous system injury.

PMID- 11248111
TI  - Estrogen increases synaptic connectivity between single presynaptic inputs and
      multiple postsynaptic CA1 pyramidal cells: a serial electron-microscopic study.
AB  - Dendritic spines are sites of the vast majority of excitatory synaptic input to
      hippocampal CA1 pyramidal cells. Estrogen has been shown to increase the density
      of dendritic spines on CA1 pyramidal cell dendrites in adult female rats. In
      parallel with increased spine density, estrogen has been shown also to increase
      the number of spine synapses formed with multiple synapse boutons (MSBs). These
      findings suggest that estrogen-induced dendritic spines form synaptic contacts
      with preexisting presynaptic boutons, transforming some previously single synapse
      boutons (SSBs) into MSBs. The goal of the current study was to determine whether
      estrogen-induced MSBs form multiple synapses with the same or different
      postsynaptic cells. To quantify same-cell vs. different-cell MSBs, we filled
      individual CA1 pyramidal cells with biocytin and serially reconstructed dendrites
      and dendritic spines of the labeled cells, as well as presynaptic boutons in
      synaptic contact with labeled and unlabeled (i.e., different-cell) spines. We
      found that the overwhelming majority of MSBs in estrogen-treated animals form
      synapses with more than one postsynaptic cell. Thus, in addition to increasing
      the density of excitatory synaptic input to individual CA1 pyramidal cells,
      estrogen also increases the divergence of input from individual presynaptic
      boutons to multiple postsynaptic CA1 pyramidal cells. These findings suggest the
      formation of new synaptic connections between previously unconnected hippocampal
      neurons.

PMID- 11248110
TI  - An N-methyl-D-aspartate receptor channel blocker with neuroprotective activity.
AB  - Excitotoxicity, resulting from sustained activation of glutamate receptors of the
      N-methyl-d-aspartate (NMDA) subtype, is considered to play a causative role in
      the etiology of ischemic stroke and several neurodegenerative diseases. The NMDA
      receptor is therefore a target for the development of neuroprotective agents.
      Here, we identify an N-benzylated triamine (denoted as NBTA) as a highly
      selective and potent NMDA-receptor channel blocker selected by screening a
      reduced dipeptidomimetic synthetic combinatorial library. NBTA blocks recombinant
      NMDA receptors expressed in Xenopus laevis oocytes with a mean IC(50) of 80 nM;
      in contrast, it does not block GluR1, a glutamate receptor of the non-NMDA
      subtype. The blocking activity of NBTA on NMDA receptors exhibits the
      characteristics of an open-channel blocker: (i) no competition with agonists,
      (ii) voltage dependence, and (iii) use dependence. Significantly, NBTA protects
      rodent hippocampal neurons from NMDA receptor, but not kainate receptor-mediated
      excitotoxic cell death, in agreement with its selective action on the
      corresponding recombinant receptors. Mutagenesis data indicate that the N site, a
      key asparagine on the M2 transmembrane segment of the NR1 subunit, is the main
      determinant of the blocker action. The results highlight the potential of this
      compound as a neuroprotectant.

PMID- 11248112
TI  - Inactivating one hippocampus impairs avoidance of a stable room-defined place
      during dissociation of arena cues from room cues by rotation of the arena.
AB  - Unilateral intrahippocampal injections of tetrodotoxin were used to temporarily
      inactivate one hippocampus during specific phases of training in an active
      allothetic place avoidance task. The rat was required to use landmarks in the
      room to avoid a room-defined sector of a slowly rotating circular arena. The
      continuous rotation dissociated room cues from arena cues and moved the arena
      surface through a part of the room in which foot-shock was delivered. The rat had
      to move away from the shock zone to prevent being transported there by the
      rotation. Unilateral hippocampal inactivations profoundly impaired acquisition
      and retrieval of the allothetic place avoidance. Posttraining unilateral
      hippocampal inactivation also impaired performance in subsequent sessions. This
      allothetic place avoidance task seems more sensitive to hippocampal disruption
      than the standard water maze task because the same unilateral hippocampal
      inactivation does not impair performance of the variable-start, fixed hidden goal
      task after procedural training. The results suggest that the hippocampus not only
      encodes allothetic relationships amongst landmarks, it also organizes perceived
      allothetic stimuli into systems of mutually stable coordinates. The latter
      function apparently requires greater hippocampal integrity.

PMID- 11248113
TI  - Substratal idiothetic navigation of rats is impaired by removal or devaluation of
      extramaze and intramaze cues.
AB  - The spatial orientation of vertebrates is implemented by two complementary
      mechanisms: allothesis, processing the information about spatial relationships
      between the animal and perceptible landmarks, and idiothesis, processing the
      substratal and inertial information produced by the animal's active or passive
      movement through the environment. Both systems allow the animal to compute its
      position with respect to perceptible landmarks and to the already traversed
      portion of the path. In the present study, we examined the properties of
      substratal idiothesis deprived of relevant exteroceptive information. Rats
      searching for food pellets in an arena formed by a movable inner disk and a
      peripheral immobile belt were trained in darkness to avoid a 60 degrees sector;
      rats that entered this sector received a mild foot shock. The punished sector was
      defined in the substratal idiothetic frame, and the rats had to determine the
      location of the shock sector with the use of substratal idiothesis only, because
      all putative intramaze cues were made irrelevant by angular displacements of the
      disk relative to the belt. Striking impairment of place avoidance by this
      "shuffling procedure" indicates that effective substratal idiothesis must be
      updated by exteroceptive intramaze cues.

PMID- 11248114
TI  - CA1-specific N-methyl-D-aspartate receptor knockout mice are deficient in solving
      a nonspatial transverse patterning task.
AB  - In both humans and animals, the hippocampus is critical to memory across
      modalities of information (e.g., spatial and nonspatial memory) and plays a
      critical role in the organization and flexible expression of memories. Recent
      studies have advanced our understanding of cellular basis of hippocampal
      function, showing that N-methyl-d-aspartate (NMDA) receptors in area CA1 are
      required in both the spatial and nonspatial domains of learning. Here we examined
      whether CA1 NMDA receptors are specifically required for the acquisition and
      flexible expression of nonspatial memory. Mice lacking CA1 NMDA receptors were
      impaired in solving a transverse patterning problem that required the
      simultaneous acquisition of three overlapping odor discriminations, and their
      impairment was related to an abnormal strategy by which they failed to adequately
      sample and compare the critical odor stimuli. By contrast, they performed
      normally, and used normal stimulus sampling strategies, in the concurrent
      learning of three nonoverlapping concurrent odor discriminations. These results
      suggest that CA1 NMDA receptors play a crucial role in the encoding and flexible
      expression of stimulus relations in nonspatial memory.

PMID- 11248115
TI  - Mice transgenically overexpressing sulfonylurea receptor 1 in forebrain resist
      seizure induction and excitotoxic neuron death.
AB  - The ability of the sulfonylurea receptor (SUR) 1 to suppress seizures and
      excitotoxic neuron damage was assessed in mice transgenically overexpressing this
      receptor. Fertilized eggs from FVB mice were injected with a construct containing
      SUR cDNA and a calcium-calmodulin kinase IIalpha promoter. The resulting mice
      showed normal gross anatomy, brain morphology and histology, and locomotor and
      cognitive behavior. However, they overexpressed the SUR1 transgene, yielding a 9-
      to 12-fold increase in the density of [(3)H]glibenclamide binding to the cortex,
      hippocampus, and striatum. These mice resisted kainic acid-induced seizures,
      showing a 36% decrease in average maximum seizure intensity and a 75% survival
      rate at a dose that killed 53% of the wild-type mice. Kainic acid-treated
      transgenic mice showed no significant loss of hippocampal pyramidal neurons or
      expression of heat shock protein 70, whereas wild-type mice lost 68-79% of
      pyramidal neurons in the CA1-3 subfields and expressed high levels of heat shock
      protein 70 after kainate administration. These results indicate that the
      transgenic overexpression of SUR1 alone in forebrain structures significantly
      protects mice from seizures and neuronal damage without interfering with
      locomotor or cognitive function.

PMID- 11248117
TI  - Insulin promotes rapid delivery of N-methyl-D- aspartate receptors to the cell
      surface by exocytosis.
AB  - Insulin potentiates N-methyl-d-aspartate receptors (NMDARs) in neurons and
      Xenopus oocytes expressing recombinant NMDARs. The present study shows that
      insulin induced (i) an increase in channel number times open probability (nP(o))
      in outside-out patches excised from Xenopus oocytes, with no change in mean open
      time, unitary conductance, or reversal potential, indicating an increase in n
      and/or P(o); (ii) an increase in charge transfer during block of NMDA-elicited
      currents by the open channel blocker MK-801, indicating increased number of
      functional NMDARs in the cell membrane with no change in P(o); and (iii)
      increased NR1 surface expression, as indicated by Western blot analysis of
      surface proteins. Botulinum neurotoxin A greatly reduced insulin potentiation,
      indicating that insertion of new receptors occurs via SNARE-dependent exocytosis.
      Thus, insulin potentiation occurs via delivery of new channels to the plasma
      membrane. NMDARs assembled from mutant subunits lacking all known sites of
      tyrosine and serine/threonine phosphorylation in their carboxyl-terminal tails
      exhibited robust insulin potentiation, suggesting that insulin potentiation does
      not require direct phosphorylation of NMDAR subunits. Because insulin and insulin
      receptors are localized to glutamatergic synapses in the hippocampus, insulin
      regulated trafficking of NMDARs may play a role in synaptic transmission and
      plasticity, including long-term potentiation.

PMID- 11248116
TI  - Activation of Trk neurotrophin receptors in the absence of neurotrophins.
AB  - Neurotrophins regulate neuronal cell survival and synaptic plasticity through
      activation of Trk receptor tyrosine kinases. Binding of neurotrophins to Trk
      receptors results in receptor autophosphorylation and downstream phosphorylation
      cascades. Here, we describe an approach to use small molecule agonists to
      transactivate Trk neurotrophin receptors. Activation of TrkA receptors in PC12
      cells and TrkB in hippocampal neurons was observed after treatment with
      adenosine, a neuromodulator that acts through G protein-coupled receptors. These
      effects were reproduced by using the adenosine agonist CGS 21680 and were
      counteracted with the antagonist ZM 241385, indicating that this transactivation
      event by adenosine involves adenosine 2A receptors. The increase in Trk activity
      could be inhibited by the use of the Src family-specific inhibitor, PP1, or
      K252a, an inhibitor of Trk receptors. In contrast to other G protein-coupled
      receptor transactivation events, adenosine used Trk receptor signaling with a
      longer time course. Moreover, adenosine activated phosphatidylinositol 3
      kinase/Akt through a Trk-dependent mechanism that resulted in increased cell
      survival after nerve growth factor or brain-derived neurotrophic factor
      withdrawal. Therefore, adenosine acting through the A(2A) receptors exerts a
      trophic effect through the engagement of Trk receptors. These results provide an
      explanation for neuroprotective actions of adenosine through a unique signaling
      mechanism and raise the possibility that small molecules may be used to elicit
      neurotrophic effects for the treatment of neurodegenerative diseases.

PMID- 11248118
TI  - A method for soluble overexpression of the alpha7 nicotinic acetylcholine
      receptor extracellular domain.
AB  - We describe the construction of a soluble protein carrying the N-terminal
      extracellular domain (ECD) of the alpha7 subunit of the nicotinic acetylcholine
      receptor. The approach was to fuse the alpha7 ECD at the C and N termini of
      several monomeric and pentameric soluble carrier proteins and to investigate the
      soluble expression of the product in Escherichia coli. An initial screening of
      six carrier proteins resulted in the selection of a fusion protein comprising,
      from the N to the C terminus, the maltose binding protein, a 17-aa linker
      containing an enterokinase binding site, and the alpha7 ECD. This protein is
      soluble upon expression in bacteria and is purified by affinity chromatography.
      It binds the competitive nicotinic antagonist alpha-bungarotoxin with 2.5 microM
      affinity and displays a CD spectrum corresponding to a folded protein. The method
      might be suitable to produce large quantities of protein for crystallization and
      immunochemical experiments.

PMID- 11248119
TI  - Genetically altered AMPA-type glutamate receptor kinetics in interneurons disrupt
      long-range synchrony of gamma oscillation.
AB  - Gamma oscillations synchronized between distant neuronal populations may be
      critical for binding together brain regions devoted to common processing tasks.
      Network modeling predicts that such synchrony depends in part on the fast time
      course of excitatory postsynaptic potentials (EPSPs) in interneurons, and that
      even moderate slowing of this time course will disrupt synchrony. We generated
      mice with slowed interneuron EPSPs by gene targeting, in which the gene encoding
      the 67-kDa form of glutamic acid decarboxylase (GAD67) was altered to drive
      expression of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)
      glutamate receptor subunit GluR-B. GluR-B is a determinant of the relatively slow
      EPSPs in excitatory neurons and is normally expressed at low levels in gamma
      aminobutyric acid (GABA)ergic interneurons, but at high levels in the GAD-GluR-B
      mice. In both wild-type and GAD-GluR-B mice, tetanic stimuli evoked gamma
      oscillations that were indistinguishable in local field potential recordings.
      Remarkably, however, oscillation synchrony between spatially separated sites was
      severely disrupted in the mutant, in association with changes in interneuron
      firing patterns. The congruence between mouse and model suggests that the rapid
      time course of AMPA receptor-mediated EPSPs in interneurons might serve to allow
      gamma oscillations to synchronize over distance.

PMID- 11248120
TI  - Most central nervous system D2 dopamine receptors are coupled to their effectors
      by Go.
AB  - We reported previously that Go-deficient mice develop severe neurological defects
      that include hyperalgesia, a generalized tremor, lack of coordination, and a
      turning syndrome somewhat reminiscent of unilateral lesions of the dopaminergic
      nigro-striatal pathway. By using frozen coronal sections of serially sectioned
      brains of normal and Go-deficient mice, we studied the ability of several G
      protein coupled receptors to promote binding of GTPgammaS to G proteins and the
      ability of GTP to promote a shift in the affinity of D2 dopamine receptor for its
      physiologic agonist dopamine. We found a generalized, but not abolished reduction
      in agonist-stimulated binding of GTPgammaS to frozen brain sections, with no
      significant left-right differences. Unexpectedly, the ability of GTP to regulate
      the binding affinity of dopamine to D2 receptors (as seen in in situ
      [(35)S]sulpiride displacement curves) that was robust in control mice, was absent
      in Go-deficient mice. The data suggest that most of the effects of the Gi/Go
      coupled D2 receptors in the central nervous system are mediated by Go instead of
      Gi1, Gi2, or Gi3. In agreement with this, the effect of GTP on dopamine binding
      to D2 receptors in double Gi1 plus Gi2- and Gi1 plus Gi3-deficient mice was
      essentially unaffected.

PMID- 11248121
TI  - Nitric oxide-induced cytostasis and cell cycle arrest of a human breast cancer
      cell line (MDA-MB-231): potential role of cyclin D1.
AB  - DETA-NONOate, a nitric oxide (NO) donor, induced cytostasis in the human breast
      cancer cells MDA-MB-231, and the cells were arrested in the G(1) phase of the
      cell cycle. This cytostatic effect of the NO donor was associated with the down
      regulation of cyclin D1 and hypophosphorylation of the retinoblastoma protein. No
      changes in the levels of cyclin E or the catalytic partners of these cyclins,
      CDK2, CDK4, or CDK6, were observed. This NO-induced cytostasis and decrease in
      cyclin D1 was reversible for up to 48 h of DETA-NONOate (1 mM) treatment. DETA
      NONOate (1 mM) produced a steady-state concentration of 0.5 microM of NO over a
      24-h period. Synchronized population of the cells exposed to DETA-NONOate
      remained arrested at the G(1) phase of the cell cycle whereas untreated control
      cells progressed through the cell cycle after serum stimulation. The cells
      arrested at the G(1) phase after exposure to the NO donor had low cyclin D1
      levels compared with the control cells. The levels of cyclin E and CDK4, however,
      were similar to the control cells. The decline in cyclin D1 protein preceded the
      decrease of its mRNA. This decline of cyclin D1 was due to a decrease in its
      synthesis induced by the NO donor and not due to an increase in its degradation.
      We conclude that down-regulation of cyclin D1 protein by DETA-NONOate played an
      important role in the cytostasis and arrest of these tumor cells in the G(1)
      phase of the cell cycle.

PMID- 11248123
TI  - A conditional probability analysis of cystic fibrosis transmembrane conductance
      regulator gating indicates that ATP has multiple effects during the gating cycle.
AB  - ATP-binding cassette (ABC) transporters bind and hydrolyze ATP. In the cystic
      fibrosis transmembrane conductance regulator Cl(-) channel, this interaction with
      ATP generates a gating cycle between a closed (C) and two open (O1 and O2)
      conformations. To understand better how ATP controls channel activity, we
      examined gating transitions from the C to the O1 and O2 states and from these
      open states to the C conformation. We made three main observations. First, we
      found that the channel can open into either the O1 or O2 state, that the
      frequency of transitions to both states was increased by ATP concentration, and
      that ATP increased the relative proportion of openings into O1 vs. O2. These
      results indicate that ATP can interact with the closed state to open the channel
      in at least two ways, which may involve binding to nucleotide-binding domains
      (NBDs) NBD1 and NBD2. Second, ATP prolonged the burst duration and altered the
      way in which the channel closed. These data suggest that ATP also interacts with
      the open channel. Third, the channel showed runs of specific types of open-closed
      transitions. This finding suggests a mechanism with more than one cycle of gating
      transitions. These data suggest models to explain how ATP influences
      conformational transitions in cystic fibrosis transmembrane conductance regulator
      and perhaps other ABC transporters.

PMID- 11248122
TI  - Testosterone inhibits early atherogenesis by conversion to estradiol: critical
      role of aromatase.
AB  - The effects of testosterone on early atherogenesis and the role of aromatase, an
      enzyme that converts testosterone to estrogens, were assessed in low density
      lipoprotein receptor-deficient male mice fed a Western diet. Castration of male
      mice increased the extent of fatty streak lesion formation in the aortic origin
      compared with testes-intact animals. Administration of anastrazole, a selective
      aromatase inhibitor, to testes-intact males increased lesion formation to the
      same extent as that observed with orchidectomized animals. Testosterone
      supplementation of orchidectomized animals reduced lesion formation when compared
      with orchidectomized animals receiving the placebo. This attenuating effect of
      testosterone was not observed when the animals were treated simultaneously with
      the aromatase inhibitor. The beneficial effects of testosterone on early
      atherogenesis were not explained by changes in lipid levels. Estradiol
      administration to orchidectomized males attenuated lesion formation to the same
      extent as testosterone administration. Aromatase was expressed in the aorta of
      these animals as assessed by reverse transcription-PCR and immunohistochemistry.
      These results indicate that testosterone attenuates early atherogenesis most
      likely by being converted to estrogens by the enzyme aromatase expressed in the
      vessel wall.

PMID- 11248124
TI  - Competitive regulation of CaT-like-mediated Ca2+ entry by protein kinase C and
      calmodulin.
AB  - A finely tuned Ca(2+) signaling system is essential for cells to transduce
      extracellular stimuli, to regulate growth, and to differentiate. We have recently
      cloned CaT-like (CaT-L), a highly selective Ca(2+) channel closely related to the
      epithelial calcium channels (ECaC) and the calcium transport protein CaT1. CaT-L
      is expressed in selected exocrine tissues, and its expression also strikingly
      correlates with the malignancy of prostate cancer. The expression pattern and
      selective Ca(2+) permeation properties suggest an important function in Ca(2+)
      uptake and a role in tumor progression, but not much is known about the
      regulation of this subfamily of ion channels. We now demonstrate a biochemical
      and functional mechanism by which cells can control CaT-L activity. CaT-L is
      regulated by means of a unique calmodulin binding site, which, at the same time,
      is a target for protein kinase C-dependent phosphorylation. We show that Ca(2+)
      dependent calmodulin binding to CaT-L, which facilitates channel inactivation,
      can be counteracted by protein kinase C-mediated phosphorylation of the
      calmodulin binding site.

PMID- 11248125
TI  - Single point mutations affect fatty acid block of human myocardial sodium channel
      alpha subunit Na+ channels.
AB  - Suppression of cardiac voltage-gated Na(+) currents is probably one of the
      important factors for the cardioprotective effects of the n-3 polyunsaturated
      fatty acids (PUFAs) against lethal arrhythmias. The alpha subunit of the human
      cardiac Na(+) channel (hH1(alpha)) and its mutants were expressed in human
      embryonic kidney (HEK293t) cells. The effects of single amino acid point
      mutations on fatty acid-induced inhibition of the hH1(alpha) Na(+) current
      (I(Na)) were assessed. Eicosapentaenoic acid (EPA, C20:5n-3) significantly
      reduced I(Na) in HEK293t cells expressing the wild type, Y1767K, and F1760K of
      hH1(alpha) Na(+) channels. The inhibition was voltage and concentration-dependent
      with a significant hyperpolarizing shift of the steady state of I(Na). In
      contrast, the mutant N406K was significantly less sensitive to the inhibitory
      effect of EPA. The values of the shift at 1, 5, and 10 microM EPA were
      significantly smaller for N406K than for the wild type. Coexpression of the
      beta(1) subunit and N406K further decreased the inhibitory effects of EPA on
      I(Na) in HEK293t cells. In addition, EPA produced a smaller hyperpolarizing shift
      of the V(1/2) of the steady-state inactivation in HEK293t cells coexpressing the
      beta(1) subunit and N406K. These results demonstrate that substitution of
      asparagine with lysine at the site of 406 in the domain-1-segment-6 region (D1
      S6) significantly decreased the inhibitory effect of PUFAs on I(Na), and
      coexpression with beta(1) decreased this effect even more. Therefore, asparagine
      at the 406 site in hH1(alpha) may be important for the inhibition by the PUFAs of
      cardiac voltage-gated Na(+) currents, which play a significant role in the
      antiarrhythmic actions of PUFAs.

PMID- 11248126
TI  - In vitro assembly of phytochrome B apoprotein with synthetic analogs of the
      phytochrome chromophore.
AB  - Phytochrome B (PhyB), one of the major photosensory chromoproteins in plants,
      mediates a variety of light-responsive developmental processes in a
      photoreversible manner. To analyze the structural requirements of the chromophore
      for the spectral properties of PhyB, we have designed and chemically synthesized
      20 analogs of the linear tetrapyrrole (bilin) chromophore and reconstituted them
      with PhyB apoprotein (PHYB). The A-ring acts mainly as the anchor for ligation to
      PHYB, because the modification of the side chains at the C2 and C3 positions did
      not significantly influence the formation or difference spectra of adducts. In
      contrast, the side chains of the B- and C-rings are crucial to position the
      chromophore properly in the chromophore pocket of PHYB and for photoreversible
      spectral changes. The side-chain structure of the D-ring is required for the
      photoreversible spectral change of the adducts. When methyl and ethyl groups at
      the C17 and C18 positions are replaced with an n-propyl, n-pentyl, or n-octyl
      group, respectively, the photoreversible spectral change of the adducts depends
      on the length of the side chains. From these studies, we conclude that each
      pyrrole ring of the linear tetrapyrrole chromophore plays a different role in
      chromophore assembly and the photochromic properties of PhyB.

PMID- 11248130
TI  - Ozone-induced mucous cell metaplasia.
AB  - The article highlighted in this issue is "Endotoxin enhancement of ozone-induced
      mucous cell metaplasia is neutrophil-dependent in rat nasal epithelium," by James
      G. Wagner, Steven J. Van Dyken, Jon A. Hotchkiss, and Jack R. Harkema (pp. 338
      347).

PMID- 11248131
TI  - Pare's law: the second law of toxicology.

PMID- 11248127
TI  - Live attenuated HIV vaccines: predicting the tradeoff between efficacy and
      safety.
AB  - The utility of live attenuated vaccines for controlling HIV epidemics is being
      debated. Live attenuated HIV vaccines (LAHVs) could be extremely effective in
      protecting against infection with wild-type strains, but may not be completely
      safe as the attenuated strain could cause AIDS in some vaccinated individuals. We
      present a theoretical framework for evaluating the consequences of the tradeoff
      between vaccine efficacy (in terms of preventing new infections with wild-type
      strains) and safety (in terms of vaccine-induced AIDS deaths). We use our
      framework to predict, for Zimbabwe and Thailand, the epidemiological impact of
      1,000 different (specified by efficacy and safety characteristics) LAHVs. We
      predict that paradoxically: (i) in Zimbabwe (where transmission is high) LAHVs
      would significantly decrease the AIDS death rate, but (ii) in Thailand (where
      transmission is low) exactly the same vaccines (in terms of efficacy and safety
      characteristics) would increase the AIDS death rate. Our results imply that a
      threshold transmission rate exists that determines whether any given LAHV has a
      beneficial or a detrimental impact. We also determine the vaccine perversity
      point, which is defined in terms of the fraction of vaccinated individuals who
      progress to AIDS as a result of the vaccine strain. Vaccination with any LAHV
      that causes more than 5% of vaccinated individuals to progress to AIDS in 25
      years would, even 50 years later, lead to perversity (i.e., increase the annual
      AIDS death rate) in Thailand; these same vaccines would lead to decreases in the
      annual AIDS death rate in Zimbabwe.

PMID- 11248132
TI  - A physiologically based model for the ingestion of chromium(III) and chromium(VI)
      by humans.
AB  - A physiologically based model of human chromium kinetics has been developed,
      based on an existing physiologically based model of human body and bone growth
      (O'Flaherty, 1993, Toxicol. Appl. Pharmacol. 118, 16-29; 1995a, Toxicol. Appl.
      Pharmacol. 131, 297-308; 2000, Toxicol. Sci. 55, 171-18) and an existing
      physiologically based model of chromium kinetics in rats (O'Flaherty, 1996,
      Toxicol. Appl. Pharmacol. 138, 54-64). Key features of the adapted model,
      specific to chromium, include differential absorption of Cr(VI) and Cr(III),
      rapid reduction of Cr(VI) to Cr(III) in all body fluids and tissues, modest
      incorporation of chromium into bone, and concentration-dependent urinary
      clearance consistent with parallel renal processes that conserve chromium
      efficiently at ambient exposure levels. The model does not include a physiologic
      lung compartment, but it can be used to estimate an upper limit on pulmonary
      absorption of inhaled chromium. The model was calibrated against blood and urine
      chromium concentration data from a group of controlled studies in which adult
      human volunteers drank solutions generally containing up to 10 mg/day of soluble
      inorganic salts of either Cr(III) (chromic chloride, CrCl(3)) or Cr(VI)
      (potassium dichromate, K(2)Cr(2)O(7)) (Finley et al., 1997, Toxicol. Appl.
      Pharmacol. 142, 151-159; Kerger et al., 1996, Toxicol. Appl. Pharmacol. 141, 145
      158; Paustenbach et al., 1996, J. Toxicol. Environ. Health 49, 453-461). In one
      of the studies, in which the chromium was ingested in orange juice, urinary
      clearance was observed to be more rapid than when inorganic chromium was
      ingested. Chromium kinetics were shown not to be dependent on the oxidation state
      of the administered chromium except in respect to the amount absorbed at these
      ambient and moderate-to-high exposures. The fraction absorbed from administered
      Cr(VI) compounds was highly variable and was presumably strongly dependent on the
      degree of reduction in the gastrointestinal tract, that is, on the amount and
      nature of the stomach contents at the time of Cr(VI) ingestion. The
      physiologically based model is applicable to both single-dose oral studies and
      chronic oral exposure, in that it adequately reproduced the time dependence of
      blood plasma concentrations and rates of urinary chromium excretion in one of the
      subjects who, in a separate experiment, ingested daily 4 mg of an inorganic
      Cr(VI) salt in 5 subdivided doses of 0.8 mg each for a total of 17 days. The high
      degree of variability of fractional absorption of Cr(VI) from the
      gastrointestinal tract leads to uncertainty in the assignment of a meaningful
      value to this parameter as applied to single Cr(VI) doses. To model chronic oral
      chromium exposure at ambient or moderately above-ambient levels, the
      physiologically based model in its present form should be usable with urinary
      clearance set to a constant value of 1-2 liters/day and the gastrointestinal
      absorption rate constants set at 0.25/day for Cr(III) and 2.5/day for Cr(VI). The
      model code is given in full in the Appendix.

PMID- 11248133
TI  - Physiological modeling reveals novel pharmacokinetic behavior for inhaled
      octamethylcyclotetrasiloxane in rats.
AB  - Octamethylcyclotetrasiloxane (D4) is an ingredient in selected consumer and
      precision cleaning products. Workplace inhalation exposures may occur in some D4
      production operations. In this study, we analyzed tissue, plasma, and excreta
      time-course data following D4 inhalation in Fischer 344 rats (K. Plotzke et al.,
      2000, Drug Metab. Dispos. 28, 192-204) to assess the degree to which the
      disposition of D4 is similar to or different from that of volatile hydrocarbons
      that lack silicone substitution. We first applied a basic physiologically based
      pharmacokinetic (PBPK) model (J. C. Ramsey and M. E. Andersen, 1984, Toxicol.
      Appl. Pharmacol. 73, 159-175) to characterize the biological determinants of D4
      kinetics. Parameter estimation techniques indicated an unusual set of
      characteristics, i.e., a low blood:air (P(b:a) congruent with 0.9) and a high
      fat:blood partition coefficient (P(f:b) congruent with 550). These parameters
      were then determined experimentally by equilibrating tissue or liquid samples
      with saturated atmospheres of D4. Consistent with the estimates from the time
      course data, blood:air partition coefficients were small, ranging from 1.9 to 6.9
      in six samples. Perirenal fat:air partition coefficients were large, from 1400 to
      2500. The average P(f:b) was determined to be 485. This combination of
      partitioning characteristics leads to rapid exhalation of free D4 at the
      cessation of the inhalation exposure followed by a much slower redistribution of
      D4 from fat and tissue storage compartments. The basic PK model failed to
      describe D4 tissue kinetics in the postexposure period and had to be expanded by
      adding deep-tissue compartments in liver and lung, a mobile chylomicron-like
      lipid transport pool in blood, and a second fat compartment. Model parameters for
      the refined model were optimized using single-exposure data in male and female
      rats exposed at three concentrations: 7, 70, and 700 ppm. With inclusion of
      induction of D4 metabolism at 700 ppm (3-fold in males, 1-fold in females), the
      parameter set from the single exposures successfully predicted PK results from 14
      day multiple exposures at 7 and 700 ppm. A common parameter set worked for both
      genders. Despite its very high lipophilicity, D4 does not show prolonged
      retention because of high hepatic and exhalation clearance. The high lipid
      solubility, low blood:air partition coefficient, and plasma lipid storage with D4
      led to novel distributional characteristics not previously noted for inhaled
      organic hydrocarbons. These novel characteristics were only made apparent by
      analysis of the time-course data with PBPK modeling techniques.

PMID- 11248134
TI  - Metabolism, microflora effects, and genotoxicity in haloacetic acid-treated
      cultures of rat cecal microbiota.
AB  - Haloacetic acids are by-products of drinking water disinfection. Several
      compounds in this class are genotoxic and have been identified as rodent
      hepatocarcinogens. Enzymes produced by the normal intestinal bacteria can
      transform some promutagens and procarcinogens to their biologically active forms.
      The present study was designed to investigate the influence of the cecal
      microbiota on the mutagenicity of haloacetic acids, and to look at changes in the
      microbiota populations and enzyme activities associated with exposure to
      haloacetic acids. PYG medium containing 1 mg/ml of monochloroacetic (MCA),
      monobromoacetic (MBA), dichloroacetic (DCA), dibromoacetic (DBA), trichloroacetic
      (TCA), tribromoacetic (TBA), or bromochloroacetic (BCA) acid was inoculated with
      rat cecal homogenate and incubated anaerobically at 37 degrees C. Growth curves
      were performed with enumeration of the microflora populations on selective media.
      Mutagenicity in a Salmonella microsuspension bioassay was determined after
      incubation for various lengths of time, with or without the cecal microbiota. At
      15 h of incubation, enzyme assays determined the activities for beta
      glucuronidase, beta-galactosidase, beta-glucosidase, azoreductase,
      nitroreductase, dechlorinase, and dehydrochlorinase. The haloacetic acids, with
      the exception of BCA, were toxic to the cecal microbiota, and especially to the
      enterococci. DBA, TBA, and BCA were mutagenic in the microsuspension assay, but
      the presence of the intestinal flora did not significantly alter the
      mutagenicity. BCA increased the activities of several enzymes, and therefore has
      the potential to affect the biotransformation of co-exposed compounds.

PMID- 11248135
TI  - Influence of dietary manganese on the pharmacokinetics of inhaled manganese
      sulfate in male CD rats.
AB  - Concerns exist as to whether individuals with relative manganese deficiency or
      excess may be at increased risk for manganese toxicity following inhalation
      exposure. The objective of this study was to determine whether manganese body
      burden influences the pharmacokinetics of inhaled manganese sulfate (MnSO(4)).
      Postnatal day (PND) 10 rats were placed on either a low (2 ppm), sufficient (10
      ppm), or high (100 ppm) manganese diet. The feeding of the 2 ppm manganese diet
      was associated with a number of effects, including reduced body weight gain,
      decreased liver manganese concentrations, and reduced whole-body manganese
      clearance rates. Beginning on PND 77 +/- 2, male littermates were exposed 6 h/day
      for 14 consecutive days to 0, 0.092, or 0.92 mg MnSO(4)/m(3). End-of-exposure
      tissue manganese concentrations and whole-body (54)Mn elimination rates were
      determined. Male rats exposed to 0.092 mg MnSO(4)/m(3) had elevated lung
      manganese concentrations when compared to air-exposed male rats. Male rats
      exposed to 0.92 mg MnSO(4)/m(3) developed increased striatal, lung, and bile
      manganese concentrations when compared to air-exposed male rats. There were no
      significant interactions between the concentration of inhaled MnSO(4) and dietary
      manganese level on tissue manganese concentrations. Rats exposed to 0.92 mg
      MnSO(4)/m(3) also had increased (54)Mn clearance rates and shorter initial phase
      elimination half-lives when compared with air-exposed control rats. These results
      suggest that, marginally manganese-deficient animals exposed to high levels of
      inhaled manganese compensate by increasing biliary manganese excretion.
      Therefore, they do not appear to be at increased risk for elevated brain
      manganese concentrations.

PMID- 11248136
TI  - The effect of pregnancy on renal clearance of boron in humans: a study based on
      normal dietary intake of boron.
AB  - Boron occurs most frequently in nature as borates and boric acid, never as the
      free element. Its largest uses are in glass, detergents, and agriculture.
      Essential for higher plants, there is growing evidence for essentiality in
      vertebrates. Humans consume daily about a milligram of boron, mostly from fruit
      and vegetables. At high doses, boron is a developmental and reproductive toxin in
      animals. Pregnant rats were the most sensitive. An oral NOAEL of 9.6 mg B/kg/day
      was established for developmental toxicity in Sprague-Dawley rats fed boric acid.
      To extrapolate from the large, animal boron toxicity database to humans,
      especially to pregnant women, information on renal clearance of boron was needed.
      This study's purpose was to measure renal clearance of boron in pregnant and
      nonpregnant woman. In 16 second trimester women and 15 nonpregnant age-matched
      referents, dietary boron provided the blood and urine boron concentrations used
      for calculating boron clearance. The pregnant and nonpregnant boron intake was
      1.35 and 1.31 mg boron/24 h, respectively. Blood for boron, creatinine, and urea
      was collected at the start, at 2 h, and at 24 h. Urine was collected during the
      first 2 h in the Clinical Research Center and during a 22-h period outside the
      center for measurement of volume, boron, and creatinine. Renal boron clearance
      measured over the initial 2 h, the most complete urine collection period, was
      68.30ml/min/1.73 m(2) for pregnant subjects and 54.31ml/min/1.73 m(2) for
      nonpregnant subjects. Comparison of renal boron clearance with creatinine
      clearance indicated that tubular reabsorption of boron occurred in both pregnant
      and nonpregnant women.

PMID- 11248137
TI  - The effect of pregnancy on renal clearance of boron in rats given boric acid
      orally.
AB  - Boric acid (H(3)BO(3)) has been shown to cause developmental abnormalities in the
      offspring of pregnant rats. Comparative data on the renal clearance of boron (B)
      in rats and humans, both pregnant and nonpregnant, exposed to boric acid (BA)
      would reduce uncertainty in interspecies extrapolation from rats to humans. The
      purpose of this study was to evaluate the effect of pregnancy on the plasma half
      life and renal clearance of boron in Sprague-Dawley rats given a single oral dose
      of boric acid. For the half-life study, nonpregnant and pregnant (gestation day
      16) rats were given a single dose of 30 mg/kg of boric acid by gavage, and plasma
      samples were collected at 2-3 h intervals. The plasma half-life of boron was
      determined to be 2.9 +/- 0.2 and 3.2 +/- 0.3 h in nonpregnant and pregnant rats,
      respectively. In the clearance study, nonpregnant and pregnant (GD 16) rats were
      given a single gavage dose of 0.3, 3, or 30 mg/kg of boric acid. Boron clearance
      was slightly higher in pregnant rats (3.3 +/- 0.6, 3.2 +/- 0.5, and 3.4 +/- 0.5
      ml/min/kg, respectively) compared to nonpregnant rats (3.1 +/- 0.8, 3.0 +/- 0.6,
      and 3.2 +/- 0.5 ml/min/kg, respectively), but the difference was not
      statistically significant and not dose-related. Boron clearance was less than
      creatinine clearance, suggesting tubular reabsorption in both groups. In
      conclusion, pregnancy did not appear to significantly alter the renal clearance
      or the plasma half-life of boron in Sprague-Dawley rats under the conditions of
      this study.

PMID- 11248138
TI  - Chromosome 11 loss from thymic lymphomas induced in heterozygous Trp53 mice by
      phenolphthalein.
AB  - C57BL/6 p53 (+/-) N5 mice heterozygous for a null p53 allele were given
      phenolphthalein to learn more about mechanisms of carcinogenesis and to evaluate
      the p53-deficient mouse as a tool for identifying potential human carcinogens.
      DNA samples isolated from 10 phenolphthalein-induced thymic lymphomas were
      analyzed for loss of heterozygosity (LOH) at the Trp53 locus and simple sequence
      length polymorphic (SSLP) loci. The initial screening revealed remarkable results
      from only chromosome 11. Allelotyping at approximately five centiMorgan
      intervals, we found SSLP heterozygosity for C57BL/6 and 129Sv over much of
      chromosome 11. In the tumors, treatment-related LOH was apparent on chromosome 11
      at each of the 28 informative loci examined. The strain-specific polymorphism
      lost from individual tumors allowed us to deduce the distribution of alleles
      along the length of the maternal and paternal chromosomes 11. The allelic
      patterns indicate that mitotic homologous recombination occurred during
      embryogenesis if breeding protocols were carried out as described. The mitotic
      recombination observed may be attributable to p53 haploinsufficiency for normal
      suppression of mitotic recombination.

PMID- 11248139
TI  - Effects of peroxisome proliferators on antioxidant enzymes and antioxidant
      vitamins in rats and hamsters.
AB  - Peroxisome proliferators (PPs) cause hepatomegaly, peroxisome proliferation, and
      hepatocarcinogenesis in rats and mice, whereas hamsters are less responsive to
      PPs. PPs increase the activities of enzymes involved in peroxisomal beta
      oxidation and omega-hydroxylation of fatty acids, which has been hypothesized to
      result in oxidative stress. The hypothesis of this study was that differential
      modulation of antioxidant enzymes and vitamins might account for differences in
      species susceptibility to PPs. Accordingly, we measured the activities of DT
      diaphorase and superoxide dismutase (SOD) and the hepatic content of ascorbic
      acid and alpha-tocopherol in male Sprague-Dawley rats and Syrian hamsters fed 2
      doses of 3 known peroxisome proliferators (dibutyl phthalate [DBP], gemfibrozil,
      and [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (Wy-14,643) for 6,
      34, or 90 days. In untreated animals, the activity of DT-diaphorase was much
      higher in hamsters than in rats, but the control levels of SOD, ascorbic acid and
      alpha-tocopherol were similar. In rats and hamsters treated with Wy-14,643, we
      observed decreases in alpha-tocopherol content and total SOD activity. DT
      diaphorase was decreased in activity following Wy-14,643 treatment in rats at all
      time points and doses, but only sporadically affected in hamsters. Rats and
      hamsters treated with DBP demonstrated increased SOD activity at 6 days; however,
      in the rat, DBP decreased SOD activity at 90 days and alpha-tocopherol content
      was decreased throughout. In gemfibrozil treated rats and hamsters, a decrease in
      alpha-tocopherol content and an increase in DT-diaphorase activity were observed.
      In either species, no consistent trend was observed in total ascorbic acid
      content after treatment with any of the PPs. In conclusion, these data suggest
      that both rats and hamsters are compromised in antioxidant capabilities following
      PP treatment and additional hypotheses for species susceptibility should be
      considered.

PMID- 11248140
TI  - Quantitative relationship between arsenic exposure and AP-1 activity in mouse
      urinary bladder epithelium.
AB  - Because of the potential of arsenic for causing cancer in humans, and of the fact
      of widespread environmental and occupational exposure, deriving acceptable human
      limit values has been of major concern to industry as well as to regulatory
      agencies. Based upon epidemiological evidence and mechanistic studies, it has
      been argued that a non-linear dose-response model at low-level exposures is more
      appropriate for calculating risk than the more commonly employed linear-response
      models. In the present studies, dose-response relationships and recovery studies
      employing a cancer precursor marker, i.e., activating protein (AP)-1 DNA-binding
      activity, were examined in bladders of mice exposed to arsenic in drinking water
      and compared to histopathological changes and arsenic tissue levels in the same
      tissue. While AP-1 is a functionally pleomorphic transcription factor regulating
      diverse gene activities, numerous studies have indicated that activation of the
      MAP kinase pathway and subsequently increased AP-1 binding activities, is a
      precursor for arsenic-induced cancers of internal organs as well as the skin. We
      observed previously that within 8 weeks of exposure AP-1 activation occurs in
      urinary bladder tissue of mice exposed to arsenic in the drinking water. In the
      present studies, C57BL/6 mice were exposed to sodium arsenite at various
      concentrations in the drinking water for 8 consecutive weeks. Minimal but
      observable AP-1 activity occurred in bladder tissue at exposure levels below
      which histopathological changes or arsenic tissue accumulation was detected.
      Marked AP-1 DNA-binding activity only occurred at exposure levels of sodium
      arsenite above 20 microg/ml, where histopathological changes and accumulation of
      arsenic in the urinary bladder epithelium occurred. Although the experimental
      design did not allow statistical modeling of the entire dose-response curve, the
      general shape of the dose-response curve is not inconsistent with the previously
      proposed hypothesis that arsenic-induced cancer follows a non-linear dose
      response model.

PMID- 11248141
TI  - Evaluation of the male pubertal onset assay to detect testosterone and steroid
      biosynthesis inhibitors in CD rats.
AB  - The male pubertal onset assay has been recommended by the Endocrine Disrupter
      Screening and Testing Advisory Committee (EDSTAC) as an alternate Tier I
      screening assay to detect potential endocrine-active chemicals (EACs). Recently,
      this assay was evaluated by several laboratories using a variety of dosing
      schemes. This study used a 30-day dosing period to confirm and extend previous
      work on the assay's ability to detect steroid biosynthesis inhibitors. Weanling
      male rats were dosed by gavage from 21 to 50 days of age with vehicle (0.5%
      methocel) or chemicals from the following EAC classes: an androgen (testosterone
      propionate [TP], 0.1 or 0.4 mg/kg/day), a broad-spectrum steroid biosynthesis
      inhibitor (ketoconazole [KETO], 24 mg/kg/day), a 5alpha-reductase inhibitor
      (finasteride [FIN], 20 or 80 mg/kg/day), a moderately specific aromatase
      inhibitor (testolactone [TL], 220 mg/kg/day), or a highly specific aromatase
      inhibitor (fadrozole [FAD], 0.6 or 6.0 mg/kg/day). None of these treatments
      altered relative thyroid weights. However, TL, KETO, and FIN were positive for
      endocrine activity based on decreases in one or more reproductive or accessory
      sex gland organ weights. Of these three inhibitors, only TL significantly
      increased the age at PPS, indicating that PPS was less sensitive for detecting
      these EACs. Based on its profile of effects, TL may have been detected as an
      antiandrogen. TP and FAD were negative in this assay, even at doses that caused
      effects in other studies. With TP, oral administration limited assay sensitivity
      such that higher TP doses would be needed for detection. FAD decreased body
      weight gains, but did not significantly alter any other assay end points; thus,
      the capacity of this assay to detect aromatase inhibitors remains in question.

PMID- 11248142
TI  - Defining the impact of weakly estrogenic chemicals on the action of steroidal
      estrogens.
AB  - We tested whether bisphenol A (BPA) or o,p'-DDT, when combined with 17beta
      estradiol (E2), would contribute to the overall mixture effect using a yeast
      reporter gene assay, the yeast estrogen screen. Following comprehensive
      concentration-response analyses of the single agents, the pharmacologically well
      founded models of concentration addition and independent action were used to
      predict entire concentration-response relationships for mixtures of the agents
      with a variety of fixed mixture ratios, assuming additivity. For molar mixture
      ratios proportional to the levels normally found in human tissues (i.e., below
      1:5000, E2:BPA or o,p'-DDT), these predictions suggest that the effects of
      individual xenoestrogens are too weak to create an impact on the actions of
      steroidal hormones. However, at mixture ratios more in favor of the
      xenoestrogens, a significant contribution to the overall mixture effect was
      predicted. The predictions were tested experimentally. The observed combined
      effects of mixtures of E2 with either BPA or o,p'-DDT did not deviate from the
      additivity expectation. On combining E2 with either BPA or o,p'-DDT at
      approximately equieffective concentrations corresponding to molar mixture ratios
      between 1:20,000 and 1:100,000 (E2:BPA or o,p'-DDT), substantial modulations of
      the effects of E2 became discernible. The assumption that weak xenoestrogens are
      generally unable to create an impact upon the already strong effects of
      endogenous steroidal estrogens is not supported by our observations. Our studies
      indicate that the potential health implication of additive combination effects
      between xenoestrogens and steroidal estrogens deserve serious consideration.

PMID- 11248143
TI  - Locomotor and sensorimotor performance deficit in rats following exposure to
      pyridostigmine bromide, DEET, and permethrin, alone and in combination.
AB  - Since their return from Persian Gulf War (PGW), many veterans have complained of
      symptoms including muscle and joint pain, ataxia, chronic fatigue, headache, and
      difficulty with concentration. The causes of the symptoms remain unknown. Because
      these veterans were exposed to a combination of chemicals including
      pyridostigmine bromide (PB), DEET, and permethrin, we investigated the effects of
      these agents, alone and in combination, on the sensorimotor behavior and central
      cholinergic system of rats. Male Sprague-Dawley rats (200-250 gm) were treated
      with DEET (40 mg/kg, dermal) or permethrin (0.13 mg/kg, dermal), alone and in
      combination with PB (1.3 mg/kg, oral, last 15 days only), for 45 days.
      Sensorimotor ability was assessed by a battery of behavioral tests that included
      beam-walk score, beam-walk time, incline plane performance, and forepaw grip on
      days 30 and 45 following the treatment. On day 45 the animals were sacrificed,
      and plasma and CNS cholinesterase, and brain choline acetyl transferase,
      muscarinic and nicotinic acetylcholine receptors were evaluated. Animals treated
      with PB, alone or in combination with DEET and permethrin, showed a significant
      deficit in beam-walk score as well as beam-walk time as compared with controls.
      Treatment with either DEET or permethrin, alone or in combination with each
      other, did not have a significant effect on beam-walk score. All chemicals, alone
      or in combination, resulted in a significant impairment in incline plane testing
      on days 30 and 45 following treatment. Treatment with PB, DEET, or permethrin
      alone did not have any inhibitory effect on plasma or brain cholinesterase
      activities, except that PB alone caused moderate inhibition in midbrain
      acetylcholinesterase (AChE) activity. Treatment with permethrin alone caused
      significant increase in cortical and cerebellar AChE activity. A combination of
      DEET and permethrin or PB and DEET led to significant decrease in AChE activity
      in brainstem and midbrain and brainstem, respectively. A significant decrease in
      brainstem AChE activity was observed following combined exposure to PB and
      permethrin. Coexposure with PB, DEET, and permethrin resulted in significant
      inhibition in AChE in brainstem and midbrain. No effect was observed on choline
      acetyl transferase activity in brainstem or cortex, except combined exposure to
      PB, DEET, and permethrin caused a slight but significant increase in cortical
      choline acetyltransferase activity. Treatment with PB, DEET, and permethrin alone
      caused a significant increase in ligand binding for m2 muscarinic acetylcholine
      receptor (mAChR) in the cortex. Coexposure to PB, DEET, and permethrin did not
      have any effect over that of PB-induced increase in ligand binding. There was no
      significant change in ligand binding for nicotinic acetylcholine receptor (nAChR)
      associated with treatment with the chemical alone; a combination of PB and DEET
      or coexposure with PB, DEET, and permethrin caused a significant increase in
      nAChR ligand binding in the cortex. Thus, these results suggest that exposure to
      physiologically relevant doses of PB, DEET, and permethrin, alone or in
      combination, leads to neurobehavioral deficits and region-specific alterations in
      AChE and acetylcholine receptors.

PMID- 11248145
TI  - Increased tumor necrosis factor-alpha production by peripheral blood leukocytes
      from TCDD-exposed rhesus monkeys.
AB  - Previous work has shown that exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) is associated with a dose-dependent increase in the incidence and severity
      of endometriosis in the rhesus monkey. Studies also suggest that immune
      mechanisms participate in TCDD-mediated toxicity and the pathogenesis of
      endometriosis. Thirteen years after TCDD treatment was terminated, we
      characterized the phenotypic distribution of peripheral blood mononuclear cells
      (PBMC) from TCDD-exposed and -unexposed rhesus monkeys and determined the ability
      of these cells to produce cytokines and exert cytolytic activity against NK and T
      cell-sensitive cell lines. We also determined whether elevated serum levels of
      TCDD, dioxin-like PHAH congeners, and triglycerides correlated with changes in
      PBMC phenotype or function. For all animals, TCDD exposure correlated with
      increased PBMC tumor necrosis factor-alpha (TNF-alpha) secretion in response to
      stimulation by T-cell mitogen and decreased cytolytic activity against NK
      sensitive target cells. Furthermore, increased production of this cytokine by PHA
      stimulated leukocytes was associated with elevated serum triglyceride levels.
      Leukocyte TNF-alpha secretion in response to viral antigen and PBMC production of
      interferon gamma (IFNgamma), IL-6, and IL-10 following exposure to mitogen or
      antigen were unaffected by previous TCDD treatment. Although TCDD exposure was
      not associated with changes in PBMC surface antigen expression, elevated serum
      concentrations of TCDD, 1,2,3,6,7,8-hexachlorodibenzofuran and 3,3',4,4',5
      pentachlorobiphenyl correlated with increased numbers of CD3+/CD25- and CD3
      /CD25+ leukocytes and enhanced secretion of TNF-alpha by mitogen-stimulated PBMC.
      These findings indicate that TCDD-exposed rhesus monkeys with endometriosis
      exhibit long-term alterations in systemic immunity associated with elevated serum
      levels of specific PHAH congeners.

PMID- 11248144
TI  - Neurotoxicological outcomes of perinatal heptachlor exposure in the rat.
AB  - The developing nervous system has been identified as a potential target of
      pesticide exposure. Heptachlor is a cyclodiene pesticide that was widely used for
      many years, and for which inadvertent exposure to children and fetuses took place
      in the early 1980s; yet little is known regarding the developmental neurotoxicity
      of it and other cyclodienes. The aim of this study was to determine whether
      perinatal heptachlor exposure results in persistent alterations in nervous system
      function. Pregnant Sprague-Dawley dams were dosed from gestational day (GD) 12 to
      postnatal day (PND) 7, whereupon the rat pups were dosed directly until PND 21
      (group A) or PND 42 (group B). Dose levels were 0, 0.03, 0.3, or 3 mg/kg/day, po.
      There were no dose-related effects on maternal weight, litter size, or pup
      growth. GABA(A) receptor binding (using [(35)S] tert
      butylbicyclophosphorothionate; TBPS) and GABA-stimulated Cl- flux were evaluated
      in control and high-dose brain tissues taken on PND 7, 21, and 43. The B(max)
      values for [(35)S]-TBPS binding in brainstem, but not cortex, were decreased in
      female rats across all ages tested. There were no such changes in male rats, nor
      were K(D) values altered in either tissue or gender. GABA-stimulated Cl- flux was
      decreased in female cortex synaptoneurosomes only on PND 21. The ontogeny of the
      righting response (PND 2-5) was delayed in the high-dose females. All subsequent
      testing took place a week to months after dosing ceased. The functional
      observational battery (FOB) showed treatment-related, but not necessarily dose
      related, changes in different aspects of the rat's reactivity and activity
      levels. Group-A rats also showed altered within-session habituation of motor
      activity. There were no heptachlor-related differences in motor activity
      following challenge with a range of chlordiazepoxide doses. Cognitive assessments
      were conducted in both groups of rats. There were no statistically significant
      differences among treatment groups in a one-trial passive avoidance test,
      although there was a trend toward less learning. In group B, rats (both sexes),
      heptachlor altered spatial learning in the Morris water maze during two weeks of
      daily training (2 trials/day). On probe trials, heptachlor-treated rats did not
      show significant preference for the correct quadrant (all dose groups in males,
      high dose in females). These rats did not show alterations on subsequent working
      memory training (where the platform position was relearned each day). Thus,
      perinatal exposure to heptachlor produced neurochemical and persistent
      neurobehavioral changes, including alterations in spatial learning and memory.

PMID- 11248146
TI  - Endotoxin enhancement of ozone-induced mucous cell metaplasia is neutrophil
      dependent in rat nasal epithelium.
AB  - Ozone, the primary oxidant gas in photochemical smog, causes neutrophilic
      inflammation and mucous cell metaplasia (MCM) in the nasal transitional
      epithelium (NTE) of rats and monkeys. Bacterial endotoxin is another common
      airborne agent that induces acute neutrophilic inflammation, but not MCM, in NTE.
      It does, however, enhance ozone-induced MCM in rat nasal airways (Fanucchi et
      al., 1998, Toxicol. Appl. Pharmacol. 152, 1-9). In the present study, F344 rats
      exposed to filtered air or 0.5 ppm ozone (8 h/day for 3 days) were intranasally
      instilled with sterile saline or 100 microg endotoxin 24 h and 48 h after the
      third ozone exposure. To determine the role of neutrophilic inflammation in
      endotoxin-induced potentiation of the MCM caused by ozone, half of the rats were
      depleted of circulating neutrophils prior to saline or endotoxin instillations.
      Rats were killed 6 h or 3 days after the last intranasal instillation, and nasal
      tissues were processed for (1) light microscopy and morphometric analysis to
      determine the number of infiltrating neutrophils and the volume amount (density)
      of stored mucosubstances in the NTE, and (2) quantitative RT-PCR analysis of
      steady-state mucin gene (rMuc-5AC) mRNA levels in the NTE. Endotoxin induced a
      transient influx of neutrophils in both air- and ozone-exposed rats that was
      completely blocked by neutrophil depletion. Endotoxin increased rMuc-5AC mRNA
      levels in the NTE of ozone-exposed rats. Neutrophil depletion, however, had no
      effect on endotoxin-induced upregulation of mucin gene mRNA levels. Endotoxin
      enhanced the ozone-induced increase in stored mucosubstances (4-fold increase),
      but only in neutrophil-sufficient rats. These data indicate that endotoxin
      enhancement of ozone-induced upregulation of rMuc-5AC mRNA levels is neutrophil
      independent, while its effects on intraepithelial production and storage of mucus
      glycoproteins is dependent on the presence of neutrophils.

PMID- 11248147
TI  - Rapid reduction of intracellular glutathione in human bronchial epithelial cells
      exposed to occupational levels of toluene diisocyanate.
AB  - Toluene diisocyanate (TDI) is a recognized chemical asthmogen, yet the mechanism
      of this toxicity and the molecular reactions involved have not been elucidated.
      We have previously shown that TDI vapor forms adducts with the apical surface of
      the respiratory epithelium, and that it colocalizes with ciliary tubulin. In
      vitro, we have shown rapid reaction of TDI with glutathione (GSH) and transfer of
      the bisGS-TDI adduct to a sulfhydryl-containing major histocompatibility complex
      peptide. This study sought to determine if intracellular GSH is altered following
      exposure to TDI. We used the dye CellTracker Green (chloromethylfluorescein,
      CMFDA) for detection of glutathione. One-day and 6-day air-liquid cultures of
      human bronchoepithelial cells (HBE) were exposed to 20-100 ppb TDI vapor for 5,
      15, or 30 min. Cells were subsequently imaged using a confocal microscope. Both 1
      and 6-day cultures showed a decrease in intensity of the thiol staining as a
      function of the TDI exposure dose. Doses as low as 20 ppb, the current
      permissible exposure limit (PEL) to TDI, resulted in rapid (within 5 min)
      decreases in fluorescence. The decreased fluorescence was not due to cytotoxicity
      or decrease in either esterase or glutathione-S-transferase activity, enzymes
      necessary for activation of the fluorescence of CMFDA. The decrease in
      glutathione levels was verified using another fluorescent label, ThioGlo(TM) 1,
      and cell extracts. In addition, the mucus produced by 6-day air-liquid interface
      HBE cells in response to TDI exposure appeared to be protective, as HBE cells
      underlying mucus retained more fluorescence than did cells in the same cultures
      that were not covered with mucus. These results, along with previous data,
      strongly suggest that TDI enters pulmonary cells and reacts rapidly with
      intracellular GSH, and that this can occur at the current PEL of 20 ppb. This
      rapid reaction suggests the importance of cellular thiols in TDI-induced
      pulmonary disease.

PMID- 11248148
TI  - Effects of ozone exposure on nuclear factor-kappaB activation and tumor necrosis
      factor-alpha expression in human nasal epithelial cells.
AB  - In this study we investigated a possible mechanism of the human airway
      inflammatory response to inhaled ozone (O(3)). Cultures of human nasal epithelial
      (HNE) cells, initiated from excised nasal turbinates and grown on collagen-coated
      Transwell tissue culture inserts, were exposed to 120, 240, or 500 ppb O(3) for 3
      h. An electron spin resonance (ESR) signal that changed with time suggested free
      radical production in HNE cells exposed to O(3). Nuclear protein extracts were
      analyzed for the activated transcription factor NF-kappaB by electrophoretic
      mobility-shift assay (EMSA), and showed a small dose-response activation of NF
      kappaB that coincided with O(3)-induced free radical production. Basal media were
      analyzed for the presence of tumor necrosis factor-alpha (TNF-alpha) using the
      enzyme-linked immunosorbent assay (ELISA). In cultures exposed to 120 ppb O(3),
      the mean TNF-alpha concentration was not significantly different from those
      exposed to air. However, exposure to 240 and 500 ppb O(3) significantly increased
      mean TNF-alpha expression, relative to controls, 16 h after exposure. These
      results support the hypothesis that the human airway epithelium plays a role in
      directing the inflammatory response to inhaled O(3) via free radical-mediated NF
      kappaB activation.

PMID- 11248149
TI  - Acute, short-term, and subchronic oral toxicity of 1,1,1-trichloroethane in rats.
AB  - 1,1,1-Trichloroethane (TRI) is a widely used solvent that has become a frequent
      contaminant of drinking water supplies in the U.S. There is very little
      information available on the potential for oral TRI to damage the liver or to
      alter its P450 metabolic capacity. Thus, a major objective of this investigation
      was to assess the acute, short-term, and subchronic hepatotoxicity of oral TRI.
      In the acute study, male Sprague-Dawley (S-D) rats were gavaged with 0, 0.5, 1,
      2, or 4 g TRI/kg bw and killed 24 h later. No acute effects were apparent other
      than CNS depression. Other male S-D rats received 0, 0.5, 5, or 10 g TRI/kg po
      once daily for 5 consecutive days, rested for 2 days, and were dosed for 4
      additional days. Groups of the animals were sacrificed for evaluation of
      hepatotoxicity 1, 5, and 12 days after initiation of the short-term experiment.
      This dosage regimen caused numerous fatalities at 5 and 10 g/kg, but no increases
      in serum enzymes or histopathological changes in the liver. For the subchronic
      study, male S-D rats were gavaged 5 times weekly with 0, 0.5, 2.5, or 5.0 g
      TRI/kg for 50 days. The 0 and 0.5 g/kg groups were dosed for 13 weeks. A
      substantial number of rats receiving 2.5 and 5.0 g/kg died, apparently due to
      effects of repeated, protracted CNS depression. There was evidence of slight
      hepatocytotoxicity at 10 g/kg, but no progression of injury nor appearance of
      adverse effects were seen during acute or short-term exposure. Ingestion of 0.5
      g/kg over 13 weeks did not cause apparent CNS depression, body or organ weight
      changes, clinical chemistry abnormalities, histopathological changes in the
      liver, or fatalities. Additional experiments did reveal that 0.5 g/kg and higher
      doses induced hepatic microsomal cytochrome P450IIE1 (CYP2E1) in a dose- and time
      dependent manner. Induction of CYP2E1 activity occurred sooner, but was of
      shorter duration than CYP2B1/2 induction. CYP1A1 activity was not enhanced. In
      summary, 0.5 g/kg po was the acute, short-term, and subchronic NOAEL for TRI, for
      effects other than transient CYP2E1 induction, under the conditions of this
      investigation. Oral TRI appears to have very limited capacity to induce P450s or
      to cause liver injury in male S-D rats, even when administered repeatedly by
      gavage in near-lethal or lethal dosages under conditions intended to maximize
      hepatic effects.

PMID- 11248150
TI  - Short-Term (13-week) toxicity study of 5-bromo-6-methoxy-5,6-dihydro-3'
      azidothymidine-5'-(p-bromophenyl) methoxyalaninyl phosphate (WHI-07), a novel
      anti-HIV and contraceptive agent, in B6C3F1 mice.
AB  - The zidovudine derivative, WHI-07 (5-bromo-6-methoxy-5,6-dihydro-3'
      azidothymidine-5'-(p-bromophenyl) methoxyalaninyl phosphate), is a dual-function
      spermicidal agent with potent anti-HIV activity. In this study, groups of 20
      female B6C3F1 mice were exposed intravaginally to a gel microemulsion containing
      0, 0.5, 1.0, or 2.0% WHI-07, 5 days per week for 13 consecutive weeks. On a molar
      basis, these concentrations of WHI-07 are 1400- to 5700-times higher than its
      spermicidal EC(50) and 1.4 x 10(6) to 5.7 x 10(6) times higher than its in vitro
      anti-HIV IC(50). After 13 weeks of intravaginal treatment, mice were evaluated
      for toxicity. The endpoints that were used for evaluation included survival, body
      weight, hematologic and clinical chemistry profiles, absolute and relative organ
      weights, and histopathology. No effects related to WHI-07 treatments were
      observed on survival, mean body weight, and mean body-weight gain. Repeated
      intravaginal exposure of mice to WHI-07 for 13 weeks had no toxicologically
      significant effect on organ weights, and did not cause any adverse changes in
      hematology parameters or blood chemistry profiles. Extensive histopathologic
      examination of tissues showed no lesions of pathologic significance. Thus,
      intravaginal application of WHI-07, for up to 13 weeks, does not cause systemic
      toxicity.

PMID- 11248151
TI  - Fumonisin B(1) increases serum sphinganine concentration but does not alter serum
      sphingosine concentration or induce cardiovascular changes in milk-fed calves.
AB  - Fumonisin B(1) is the most toxic and commonly occurring form of a group of
      mycotoxins that alter sphingolipid biosynthesis and induce leukoencephalomalacia
      in horses and pulmonary edema in pigs. Purified fumonisin B(1) (1 mg/kg, iv,
      daily) increased serum sphinganine and sphingosine concentrations and decreased
      cardiovascular function in pigs within 5 days. We therefore examined whether the
      same dosage schedule of fumonisin B(1) produced a similar effect in calves. Ten
      milk-fed male Holstein calves were instrumented to obtain blood and
      cardiovascular measurements. Treated calves (n = 5) were administered purified
      fumonisin B(1) at 1 mg/kg, iv, daily for 7 days and controls (n = 5) were
      administered 10 ml 0.9% NaCl, iv, daily. Each calf was euthanized on day 7. In
      treated calves, serum sphinganine concentration increased from day 3 onward (day
      7, 0.237 +/- 0.388 micromol/l; baseline, 0.010 +/- 0.007 micromol/l; mean +/-
      SD), whereas, serum sphingosine concentration was unchanged (day 7, 0.044 +/-
      0.065 micromol/l; baseline, 0.021 +/- 0.025 micromol/l). Heart rate, cardiac
      output, stroke volume, mean arterial pressure, mean pulmonary artery pressure,
      pulmonary artery wedge pressure, central venous pressure, plasma volume, base
      apex electrocardiogram, arterial Po(2), and systemic oxygen delivery were
      unchanged in treated and control calves. Fumonisin-treated calves developed
      metabolic acidosis (arterial blood pH, 7.27 +/- 0.11; base excess, -9.1 +/- 7.6
      mEq/l), but all survived for 7 days. We conclude that calves are more resistant
      to fumonisin B(1) cardiovascular toxicity than pigs.

PMID- 11248152
TI  - Fumonisin B(1) is hepatotoxic and nephrotoxic in milk-fed calves.
AB  - Fumonisins are a group of mycotoxins that alter sphingolipid biosynthesis and
      induce leukoencephalomalacia in horses and pulmonary edema in pigs. Experimental
      administration of fumonisin induces hepatotoxicity in all species, including
      cattle, as well as nephrotoxicity in rats, rabbits, and sheep. We investigated
      the hepatotoxicity and nephrotoxicity of fumonisin B(1) to calves. Ten milk-fed
      male Holstein calves aged 7 to 14 days were instrumented to obtain blood and
      urine. Treated calves (n = 5) were administered fumonisin B(1) at 1 mg/kg, iv,
      daily and controls (n = 5) 10 ml 0.9% NaCl, iv, daily until euthanized on day 7.
      Fumonisin B(1)-treated calves were lethargic and had decreased appetite from day
      4 onward, serum biochemical evidence of severe liver and bile duct injury, and
      impaired hepatic function. Treated calves also had biochemical evidence of renal
      injury that functionally involved the proximal convoluted tubules. Sphinganine
      and sphingosine concentrations in liver, kidney, lung, heart, and skeletal muscle
      were increased in treated calves. Sphinganine, but not sphingosine, concentration
      was increased in brains of treated calves. In fumonisin B(1)-treated calves,
      hepatic lesions were characterized by disorganized hepatic cords, varying
      severity of hepatocyte apoptosis, hepatocyte proliferation, and proliferation of
      bile ductular cells. Renal lesions in treated calves consisted of vacuolar
      change, apoptosis, karyomegaly, and proliferation of proximal renal tubular
      cells, as well as dilation of proximal renal tubules, which contained cellular
      debris and protein. This is the first report of fumonisin B(1)-induced renal
      injury and organ sphingolipid alterations in cattle.

PMID- 11248153
TI  - Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast
      cancer that overexpresses HER2.
AB  - BACKGROUND: The HER2 gene, which encodes the growth factor receptor HER2, is
      amplified and HER2 is overexpressed in 25 to 30 percent of breast cancers,
      increasing the aggressiveness of the tumor. METHODS: We evaluated the efficacy
      and safety of trastuzumab, a recombinant monoclonal antibody against HER2, in
      women with metastatic breast cancer that overexpressed HER2. We randomly assigned
      234 patients to receive standard chemotherapy alone and 235 patients to receive
      standard chemotherapy plus trastuzumab. Patients who had not previously received
      adjuvant (postoperative) therapy with an anthracycline were treated with
      doxorubicin (or epirubicin in the case of 36 women) and cyclophosphamide alone
      (138 women) or with trastuzumab (143 women). Patients who had previously received
      adjuvant anthracycline were treated with paclitaxel alone (96 women) or
      paclitaxel with trastuzumab (92 women). RESULTS: The addition of trastuzumab to
      chemotherapy was associated with a longer time to disease progression (median,
      7.4 vs. 4.6 months; P<0.001), a higher rate of objective response (50 percent vs.
      32 percent, P<0.001), a longer duration of response (median, 9.1 vs. 6.1 months;
      P<0.001), a lower rate of death at 1 year (22 percent vs. 33 percent, P=0.008),
      longer survival (median survival, 25.1 vs. 20.3 months; P=0.01), and a 20 percent
      reduction in the risk of death. The most important adverse event was cardiac
      dysfunction of New York Heart Association class III or IV, which occurred in 27
      percent of the group given an anthracycline, cyclophosphamide, and trastuzumab; 8
      percent of the group given an anthracycline and cyclophosphamide alone; 13
      percent of the group given paclitaxel and trastuzumab; and 1 percent of the group
      given paclitaxel alone. Although the cardiotoxicity was potentially severe and,
      in some cases, life-threatening, the symptoms generally improved with standard
      medical management. CONCLUSIONS: Trastuzumab increases the clinical benefit of
      first-line chemotherapy in metastatic breast cancer that overexpresses HER2.

PMID- 11248154
TI  - ABO-incompatible heart transplantation in infants.
AB  - BACKGROUND: Transplantation of hearts from ABO-incompatible donors is
      contraindicated because of the risk of hyperacute rejection mediated by preformed
      antibodies in the recipient to blood-group antigens of the donor. This
      contraindication may not apply to newborn infants, who do not yet produce
      antibodies to T-cell-independent antigens, including the major blood-group
      antigens. METHODS: We studied 10 infants 4 hours to 14 months old (median, 2
      months) who had congenital heart disease or cardiomyopathy and who received heart
      transplants from donors of incompatible blood type between 1996 and 2000. Serum
      isohemagglutinin titers were measured before and after transplantation. Plasma
      exchange was performed during cardiopulmonary bypass; no other procedures for the
      removal of antibodies were used. Standard immunosuppressive therapy was given,
      and rejection was monitored by means of endomyocardial biopsy. The results were
      compared with those in 10 infants who received heart transplants from ABO
      compatible donors. RESULTS: The overall survival rate among the 10 recipients
      with ABO-incompatible donors was 80 percent, with 2 early deaths due to causes
      presumed to be unrelated to ABO incompatibility. The duration of follow-up ranged
      from 11 months to 4.6 years. Two infants had serum antibodies to antigens of the
      donor's blood group before transplantation. No hyperacute rejection occurred;
      mild humoral rejection was noted at autopsy in one of the infants with
      antibodies. No morbidity attributable to ABO incompatibility has been observed.
      Despite the eventual development of antibodies to antigens of the donor's blood
      group in two infants, no damage to the graft has occurred. Because of the use of
      ABO-incompatible donors, the mortality rate among infants on the waiting list
      declined from 58 percent to 7 percent. CONCLUSIONS: ABO-incompatible heart
      transplantation can be performed safely during infancy before the onset of
      isohemagglutinin production; this technique thus contributes to a marked
      reduction in mortality among infants on the waiting list.

PMID- 11248155
TI  - La Crosse encephalitis in children.
AB  - BACKGROUND: La Crosse encephalitis is a mosquito-borne disease that can be
      mistaken for herpes simplex encephalitis. It has been reported in 28 states but
      may be underrecognized. METHODS: We investigated the manifestations and clinical
      course of La Crosse encephalitis in 127 patients hospitalized from 1987 through
      1996. The diagnosis was established by serologic testing for IgM and IgG
      antibodies to La Crosse virus. Data were collected by chart review. RESULTS: Most
      of the patients were school-aged children (mean [+/-SD] age, 7.8+/-3.5 years;
      range, 0.5 to 15.0). Symptoms included headache, fever, and vomiting (each in 70
      percent or more of the patients), seizures (in 46 percent), and disorientation
      (in 42 percent). Thirteen percent had aseptic meningitis. Hyponatremia developed
      in 21 percent, and there were signs of increased intracranial pressure in 13
      percent. Six patients, including three with cerebral herniation, underwent
      intracranial-pressure monitoring. The 13 patients (11 percent) whose condition
      deteriorated in the hospital had decreases in serum sodium levels (P=0.007), and
      increases in body temperature (P=0.003) at the time of deterioration. At
      admission, these patients more often had a history of vomiting (P=0.047) and a
      score of 12 or lower on the Glasgow Coma Scale (P=0.02) than the others; a trend
      toward a greater prevalence of seizures at admission was also evident in this
      group (P=0.07). All the patients survived, but 15 of them (12 percent) had
      neurologic deficits at discharge. Follow-up assessments, performed in 28
      children, suggested an increase in cognitive and behavioral deficits 10 to 18
      months after the episode of encephalitis. CONCLUSIONS: La Crosse virus infection
      should be considered in children who present with aseptic meningitis or
      encephalitis. Hyponatremia and increasing body temperature may be related to
      clinical deterioration.

PMID- 11248157
TI  - Images in clinical medicine. Paclitaxel and cell division.

PMID- 11248156
TI  - Appendectomy and protection against ulcerative colitis.
AB  - BACKGROUND: A history of appendectomy is rare in patients with ulcerative
      colitis. This suggests a protective effect of appendectomy or that appendicitis
      and ulcerative colitis are alternative inflammatory responses. We sought to
      characterize this inverse relation further. METHODS: We studied a cohort of
      212,963 patients who underwent appendectomy before the age of 50 years between
      1964 and 1993 and a cohort of matched controls who were identified from the
      Swedish Inpatient Register and the nationwide census. The cohort was followed
      until 1995 for any subsequent diagnosis of ulcerative colitis. RESULTS: Patients
      who underwent appendectomy for appendicitis and mesenteric lymphadenitis had a
      low risk of ulcerative colitis (for patients with perforated appendicitis, the
      adjusted hazard ratio was 0.58 [95 percent confidence interval, 0.38 to 0.87];
      for those with nonperforated appendicitis it was 0.76 [95 percent confidence
      interval, 0.65 to 0.90]; and for those with mesenteric lymphadenitis it was 0.57
      [95 percent confidence interval, 0.36 to 0.89]). In contrast, patients who
      underwent appendectomy for nonspecific abdominal pain had the same risk of
      ulcerative colitis as the controls (adjusted hazard ratio, 1.06; 95 percent
      confidence interval, 0.74 to 1.52). For the patients who had appendicitis, an
      inverse relation with the risk of ulcerative colitis was found only for those who
      underwent surgery before the age of 20 years (P<0.001). CONCLUSIONS: Appendectomy
      for an inflammatory condition (appendicitis or lymphadenitis) but not for
      nonspecific abdominal pain is associated with a low risk of subsequent ulcerative
      colitis. This inverse relation is limited to patients who undergo surgery before
      the age of 20 years.

PMID- 11248158
TI  - Images in clinical medicine. Waldenstrom's macroglobulinemia.

PMID- 11248159
TI  - Expenditures for the care of HIV-infected patients in the era of highly active
      antiretroviral therapy.
AB  - BACKGROUND: The introduction of expensive but very effective antiviral
      medications has led to questions about the effects on the total use of resources
      for the care of patients with human immunodeficiency virus (HIV) infection. We
      examined expenditures for the care of HIV-infected patients since the
      introduction of highly active antiretroviral therapy. METHODS: We interviewed a
      random sample of 2864 patients who were representative of all American adults
      receiving care for HIV infection in early 1996, and followed them for up to 36
      months. We estimated the average expenditure per patient per month on the basis
      of self-reported information about care received. RESULTS: The mean expenditure
      was $1,792 per patient per month at base line, but it declined to $1,359 for
      survivors in 1997, since the increases in pharmaceutical expenditures were
      smaller than the reductions in hospital costs. Use of highly active
      antiretroviral therapy was independently associated with a reduction in
      expenditures. After adjustments for the interview date, clinical status, and
      deaths, the estimated annual expenditure declined from $20,300 per patient in
      1996 to $18,300 in 1998. Expenditures among subgroups of patients varied by a
      factor of as much as three. Pharmaceutical costs were lowest and hospital costs
      highest among underserved groups, including blacks, women, and patients without
      private insurance. CONCLUSIONS: The total cost of care for adults with HIV
      infection has declined since the introduction of highly active antiretroviral
      therapy. Expenditures have increased for medications but have declined for other
      services. However, there are large variations in expenditures across subgroups of
      patients.

PMID- 11248160
TI  - The cost effectiveness of combination antiretroviral therapy for HIV disease.
AB  - BACKGROUND: Combination antiretroviral therapy with a combination of three or
      more drugs has become the standard of care for patients with human
      immunodeficiency virus (HIV) infection in the United States. We estimated the
      clinical benefits and cost effectiveness of three-drug antiretroviral regimens.
      METHODS: We developed a mathematical simulation model of HIV disease, using the
      CD4 cell count and HIV RNA level as predictors of the progression of disease.
      Outcome measures included life expectancy, life expectancy adjusted for the
      quality of life, lifetime direct medical costs, and cost effectiveness in dollars
      per quality-adjusted year of life gained. Clinical data were derived from major
      clinical trials, including the AIDS Clinical Trials Group 320 Study. Data on
      costs were based on the national AIDS Cost and Services Utilization Survey, with
      drug costs obtained from the Red Book. RESULTS: For patients similar to those in
      the AIDS Clinical Trials Group 320 Study (mean CD4 cell count, 87 per cubic
      millimeter), life expectancy adjusted for the quality of life increased from 1.53
      to 2.91 years, and per-person lifetime costs increased from $45,460 to $77,300
      with three-drug therapy as compared with no therapy. The incremental cost per
      quality-adjusted year of life gained, as compared with no therapy, was $23,000.
      On the basis of additional data from other major studies, the cost-effectiveness
      ratio for three-drug therapy ranged from $13,000 to $23,000 per quality-adjusted
      year of life gained. The initial CD4 cell count and drug costs were the most
      important determinants of costs, clinical benefits, and cost effectiveness.
      CONCLUSIONS: Treatment of HIV infection with a combination of three
      antiretroviral drugs is a cost-effective use of resources.

PMID- 11248161
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 8-2001. A 61-year-old man with transient quadriplegia and apnea.

PMID- 11248162
TI  - From the molecule to the clinic--inhibiting HER2 to treat breast cancer.

PMID- 11248163
TI  - Breaching the barrier of ABO incompatibility in heart transplantation for
      infants.

PMID- 11248164
TI  - Providing antiretroviral therapy for HIV infection.

PMID- 11248165
TI  - Prospects for expanding health insurance coverage.

PMID- 11248166
TI  - Concepts in service marketing for healthcare professionals.
AB  - Patients are becoming increasingly involved in making healthcare choices as their
      burden of healthcare costs continues to escalate. At the same time, healthcare
      has entered a tightened market economy. For these reasons, the marketing of
      healthcare services has become essential for the financial survival of physicians
      and healthcare organizations. Physicians can successfully use the fundamental
      service marketing principles proven by other service industries to win patient
      satisfaction and loyalty and remain competitive in today's market economy.
      Understanding concepts such as service quality zone of tolerance, levels of
      consumer satisfaction, the branding of services, patient participation, and
      service recovery can be useful in achieving these goals.

PMID- 11248167
TI  - Melanoma thickness and histology predict sentinel lymph node status.
AB  - BACKGROUND: It remains unclear which patients with melanoma will benefit most
      from lymphatic mapping and sentinel lymphadenectomy. The purpose of this study is
      to determine whether primary melanoma histopathologic features could be applied
      to predict sentinel node status. METHODS: One hundred twelve patients underwent
      sentinel node biopsy between May 1995 and August 1999. Reported histologic
      features were assessed for predictive value by univariate and multivariate
      logistic regression. RESULTS: The sentinel node was located successfully in 105
      of the 112 patients (94%). Twenty-one of these 105 patients (20%) had sentinel
      nodes that were positive for metastatic disease. Multivariate analyses revealed
      that tumor thickness greater than 1.5 mm (P = 0.01), ulceration (P <0.01), and
      lymphovascular invasion (P = 0.05) predicted the presence of micrometastases.
      CONCLUSIONS: The presence of unfavorable histopathology such as ulceration and
      lymphovascular invasion may identify a group of patients with thin melanomas who
      would benefit from sentinel lymphadenectomy.

PMID- 11248168
TI  - Results and complications after adjustable gastric banding in a series of 250
      patients.
AB  - BACKGROUND: Morbid obesity contributes to many health risks including physical,
      emotional, and social problems. The increasing prevalence of obesity is a major
      public health concern since obesity is associated with several chronic diseases.
      Morbid obesity is the biggest independent risk factor for early mortality.
      Various options for the surgical treatment of morbid obesity have been developed
      with varying results. METHODS: Between January 1996 and December 1999, we
      operated on a series of 250 patients (200 women and 50 men) at the General
      Surgical Department of the University Hospital in Innsbruck. The parameters that
      were evaluated included age, preoperative and postoperative body mass index
      (BMI), type of surgery, and intraoperative and postoperative complications.
      RESULTS: The mean follow-up period was 12 months (range 3 to 18). The average
      preoperative weight was 135.5 kg (BMI 46.69 kg/m(2)). The average total weight
      loss was 5.5 kg per month, reaching an average total of 35 kg after one year. The
      excess weight loss (EWL) after 12 months was 72%. Complications requiring
      reoperation occurred in 8.8%. CONCLUSIONS: In the first year after laparoscopic
      adjustable gastric banding, weight reduction of the study population was
      excellent. Additionally, the complication rate was reasonable with no
      mortalities.

PMID- 11248169
TI  - Clinical utility of CEA, CA 19-9, and CA 72-4 in the follow-up of patients with
      resectable gastric cancer.
AB  - BACKGROUND: The aim of this longitudinal study was to evaluate the effectiveness
      of the serum tumor markers CEA, CA 19-9, and CA 72-4 in the early diagnosis of
      recurrence of gastric cancer. METHODS: One hundred and thirty-three patients who
      had undergone potentially curative surgery were considered. Serum samples were
      obtained preoperatively, 1 week after surgery, and at every follow-up
      examination. Mean follow-up time for the entire patient population was 41 +/- 33
      months, and 71 +/- 27 months for patients classified as disease-free. RESULTS:
      Preoperative positivity was 16% for CEA, 35% for CA 19-9, and 20% for CA 72-4.
      Recurrence of disease was found in 75 patients (56%). Marker sensitivity in
      recurrent cases was 44% for CEA, 56% for CA 19-9, and 51% for CA 72-4; the
      combined use of the three markers increased sensitivity to 87%, which reached
      100% in patients with positive preoperative levels. Marker specificity, evaluated
      in 58 disease-free patients, was 79% for CEA, 74% for CA 19-9, and 97% for CA 72
      4. CONCLUSIONS: The combined assay of CEA, CA 19-9, and CA 72-4 may be useful for
      early diagnosis of recurrence of gastric cancer; however, only CA 72-4 positivity
      should be considered a specific predictor of tumor recurrence.

PMID- 11248170
TI  - A retrospective study of diagnosis and management of mesenteric vein thrombosis.
AB  - BACKGROUND: Mesenteric vein thrombosis (MVT) is an uncommon type of intestinal
      ischemia associated with significant mortality and morbidity because of its delay
      in diagnosis. METHODS: A retrospective analysis of 9 patients treated surgically
      for MVT during 1982 to 1997 was performed. RESULTS: Nine patients underwent
      surgical therapy for intestinal ischemia due to MVT. The most common presenting
      symptom was abdominal pain with bloody diarrhea in 3 patients; preoperative
      diagnosis of MVT was suspected in 2. Radiologic tests included plain
      roentgenograms, computed axial tomography, and ultrasound. Time to surgery ranged
      from 3 hours to 7 days after admission. All patients underwent resection of
      infarcted bowel with primary anastomosis and immediate postoperative
      anticoagulation. No patient underwent a second-look operation. The postoperative
      morbidity and mortality rates were 55% and 11%, respectively. CONCLUSION:
      Diagnosis of intestinal ischemia from MVT is often delayed, and strong clinical
      suspicion and aggressive treatment are necessary in its management.

PMID- 11248172
TI  - Removal of the thrombosed prosthetic axillofemoral graft.
AB  - Late thrombosis of prosthetic graft material is rarely managed successfully by
      simple thrombectomy or thrombolytic therapy. Replacement with a new graft may be
      necessary. Although several techniques have been described, mobilizing and
      removing an old thrombosed prosthetic graft is usually extremely difficult
      because of a firm attachment to its tunnel. This attempt is more difficult
      especially for ringed grafts. We describe a simple technique of using an internal
      varicose vein stripper for the removal of such a late thrombosed axillofemoral
      spiral polytetrafluoroethylene graft and positioning a new graft into the old
      tunnel.

PMID- 11248171
TI  - Patency and flow characteristics using stapled vascular anastomoses in dialysis
      grafts.
AB  - BACKGROUND: Improving patency of hemodialysis grafts is challenging. Vascular
      stapling creates nonpenetrating anastomoses, possibly decreasing intimal
      hyperplasia. We investigated patency and flow characteristics of stapled
      hemodialysis grafts. METHODS: Eighty-six grafts (41 stapled, 45 sewn) were placed
      in 84 patients (prospective, randomized). The groups had comparable demographics.
      RESULTS: Thirty-six grafts were functioning at the study endpoint. Complications
      in both groups were similar. The primary patency (stapled, 342 days versus sewn,
      382 days; P = 0.67) and secondary patency (stapled, 513 days versus sewn, 507
      days; P = 0.76) had no significant differences. Flow characteristics were similar
      between the groups. Thrombectomies per patient-year were 1.01 for stapled grafts
      and 1.12 for sewn grafts (not significant). Stapling decreased the average
      operating time by 4.5 minutes. CONCLUSIONS: Stapled and sewn anastomoses have
      similar primary and secondary patency and flow characteristics, with minimal
      operative time differences. Stapled anastomoses are safe but had no advantage
      over sewn anastomoses in this study.

PMID- 11248173
TI  - Predicting death from ruptured abdominal aortic aneurysms.
AB  - BACKGROUND: We have previously reported preoperative and immediate postoperative
      formulae to estimate mortality in patients with ruptured abdominal aortic
      aneurysms (rAAA). In this study, we prospectively compared these formulae in
      patients with rAAA with their actual outcomes. METHODS: Information was collected
      on 134 patients from two centers over a 3-year period. Preoperative mortality
      risk was estimated using coefficients for age, level of consciousness, and
      cardiac arrest. Mortality risk in the immediate postoperative state was based on
      the presence of coagulopathy, ischemic colitis, prolonged requirement for
      inotropes, time from arrival at hospital to surgery, patient age, perioperative
      myocardial infarction, renal failure, and pre-operative hemoglobin level.
      RESULTS: The average age was 73 years (range 30 to 92 y) and 20 of 134 (15%)
      patients were women. Sixty-three patients (47%) survived. For patients with a
      calculated preoperative mortality risk of >90%, the sensitivity, specificity, and
      positive and negative predictive values were 25%, 98%, 95%, and 54%,
      respectively. For a mortality risk >80%, these values were 37%, 94%, 87%, and
      57%, respectively. For patients with an estimated immediate postoperative
      mortality risk > or = 90%, the sensitivity, specificity, and positive and
      negative predictive values were 17%, 87%, 60%, and 49%, respectively. For a
      predicted mortality > or = 80%, these values were 22%, 84%, 60%, and 50%,
      respectively. CONCLUSIONS: Our formula for predicting mortality for preoperative
      rAAA patients may be useful for patients with an estimated mortality risk >/=90%,
      based on the high positive predictive value. The formula for immediate
      postoperative rAAA patients was not useful in predicting death.

PMID- 11248174
TI  - Endotoxemia and acute-phase proteins in major abdominal surgery.
AB  - BACKGROUND: Translocation of endotoxin is a controversial issue. The ability of
      plasma to inactivate endotoxin is an indirect measure of endotoxemia. Endotoxin
      is a potent stimulator of the inflammatory response and affects the innate immune
      system. OBJECTIVE: To elucidate the kinetics of endotoxemia and the ability of
      plasma to inactivate endotoxin in patients with major abdominal operations. To
      demonstrate the early time course of the acute-phase proteins C-reactive protein
      (CRP), serum amyloid A (SAA), alpha(1)-antitrypsin, alpha(2)-macroglobulin,
      transferrin, and interleukin 6 (IL-6), and to correlate them with the amount of
      endotoxemia. METHODS: Twenty patients with elective major abdominal operation and
      10 healthy controls were investigated. Blood was collected preoperatively, during
      the operation and regularly up to 12 days after surgery. Endotoxin was measured
      by Limulus amebocyte lysate test (LAL), the ability of plasma to inactivate
      endotoxin by modified LAL, the acute-phase proteins nephelometrically, and IL-6
      by enzyme-linked immunosorbent assay (ELISA). RESULTS: Preoperative endotoxin
      plasma level (0.026 +/- 0.004 EU/mL) did not differ from healthy volunteers but
      increased during operation (0.09 +/- 0.02 EU/mL, P = 0.02). Endotoxemia peaked 1
      hour after the surgical procedure (0.16 +/- 0.03 EU/mL; P <0.0001 versus
      preoperative) and decreased to almost normal values after 48 hours. The
      capability of plasma to inactivate endotoxin was significantly reduced during
      (recovery, 0.16 +/- 0.03 EU/mL), 1 hour (0.25 +/- 0.04 EU/mL) and 24 hours (0.16
      +/- 0.02 EU/mL) after the operation compared with preoperative (0.068 +/- 0.01
      EU/mL) values. Plasma IL-6 was significantly increased for 48 hours with a peak 1
      hour after surgery (470 +/- 108 pg/mL). CRP peaked at 210 +/- 19 mg/L (P <0.0001
      versus preoperative) 48 hours after operation and was significantly elevated for
      the rest of the observation period. SAA was significantly increased 24 hours
      after surgery (249 +/- 45 mg/L) and peaked additional 48 hours later (456 +/- 86
      mg/L). alpha(1)-Antitrypsin, although a positive acute-phase protein, decreased
      initially to 1.38 +/- 0.1 g/L (preoperative, 2.33 +/- 0.18 g/L; P <0.0001) and
      increased thereafter until day 12 (3.05 +/- 0.35 g/L, P = 0.11 versus
      preoperative). The same was true for alpha(2)-macroglobulin (preoperative, 2.2 +/
      0.16 g/L; intraoperative, 1.36 +/- 0.13 g/L; day 5, 2.8 +/- 0.4 g/L).
      Transferrin decreased already during surgery (1.6 +/- 0.1 g/L versus preoperative
      2.8 +/- 0.17 g/L, P <0.0001) and remained on this level for 5 days. Correlation
      analysis revealed a relationship between endotoxemia and the ability of plasma to
      inactivate endotoxin (r = 0.67, P <0.0001) and also a relation between
      intraoperative endotoxemia on one hand and alpha(2)-macroglobulin (-0.53 > r > 
      0.6, P <0.05) as well as alpha(1)-antitrypsin (0.64 > r >0.55, P <0.05) on the
      other. CONCLUSION: Major abdominal surgery is associated with transient
      endotoxemia and a transient reduced endotoxin inactivation capacity of the
      plasma. Endotoxemia correlates with the endotoxin inactivation capacity. The
      surgical procedure causes substantial changes in plasma concentrations of acute
      phase proteins. alpha(2)-Macroglobulin and alpha(1)-antitrypsin correlate
      moderately with endotoxemia.

PMID- 11248175
TI  - Is the quality of surgical residency applicants deteriorating?
AB  - BACKGROUND: Among directors of general surgery residencies, there is a concern
      that the quality of medical students applying to surgical residencies is
      declining. METHODS: Quality of surgical applicants was assessed by several
      methods including subjective opinions determined by survey and by objective data
      including student United States Medical Licensing Examination (USMLE) scores of
      matched candidates. The number of applicants interviewed, total interviews
      granted, proportion of Alpha Omega Alpha (AOA) students, and the rank order of
      the candidates matched was obtained by survey. The survey included data on
      postgraduate year 1 (PGY-1) residents from July 1996 to July 1999. Three mailings
      were made to 226 US surgical residency programs. RESULTS: Data were obtained from
      90 programs. Surgery program directors disagreed with a survey statement that
      overall quality of applicants had declined (P <0.01), but agreed with a statement
      that activities of medical schools to enroll graduating students into primary
      care had hurt recruitment (P <0.001). Objective data revealed no change in mean
      USMLE part I scores of PGY-1 residents over the 4 years (P = 0.265, power =
      0.81). There was no change in proportion of matched residents who were AOA over
      time. The mean score of all new PGY-1 residents, the rank of the first matched
      resident, the rank of the last ranked resident, and proportion of AOA students
      was higher in programs with five or more categorical spots when compared with
      programs of at most four (P <0.001). Across all programs, there was a trend to go
      lower on the rank list to fill categorical positions over time (P <0.001).
      CONCLUSIONS: There is a perception that medical school policies act to discourage
      recruitment of quality medical students into general surgery programs, and
      surgery programs are going deeper into their rank lists to fill categorical
      positions. However, the average USMLE part I score of applicants to surgical
      residencies and proportion of AOA applicants has not decreased.

PMID- 11248176
TI  - "Tube-guided" implant of bioprosthetic shunt for hemodialysis.
AB  - Implant of a bovine-derived vascular bioprosthesis as arterio-venous shunt for
      hemodialysis may raise some problems regarding tunnel fashioning. Therefore, we
      have proposed a simple "tube-guided" technique to make implant safer and to avoid
      complications.

PMID- 11248177
TI  - Effect of preoperative biliary drainage on surgical outcome after
      pancreatoduodenectomy.
AB  - BACKGROUND: The role of preoperative biliary drainage in patients with biliary
      obstruction undergoing pancreatoduodenectomy remains controversial. Several
      authors failed to show any effect of preoperative biliary drainage, whereas
      others even reported an increased morbidity following pancreatoduodenectomy.
      METHODS: Retrospective analysis was performed in a consecutive series of 257
      patients undergoing pancreatoduodenectomy between November 1993 and November
      1999. RESULTS: Ninety-nine patients (38%) underwent preoperative biliary drainage
      for a median time period of 10 days (range 1 to 41) prior to resection.
      Cumulative postoperative morbidity was 47% (120 patients), the reoperation rate
      was 4.3% (11 patients), and mortality was 2.3% (6 patients). There was no
      difference in total morbidity, infectious complications, reoperation rate,
      mortality, or long-term survival between patients with or without preoperative
      biliary drainage. CONCLUSIONS: Preoperative biliary instrumentation and biliary
      drainage do not affect early or late outcome in patients undergoing
      pancreatoduodenectomy.

PMID- 11248178
TI  - A comparison of common bile duct pressures after botulinum toxin injection into
      the sphincter of Oddi versus biliary stenting in a canine model.
AB  - BACKGROUND: Botulinum toxin A (Botox) functionally paralyzes the sphincter of
      Oddi in both animals and humans, resulting in reduced pressures. No study,
      however, has specifically addressed common bile duct (CBD) pressures after Botox
      injection into the sphincter of Oddi with regard to treating biliary leaks and
      fistulae. The goals of this present study are to compare, versus biliary
      stenting, the change in CBD pressures after Botox injection into the sphincter of
      Oddi, as well as to evaluate the timing of onset and duration of these effects on
      sphincteric relaxation. METHODS: After midline laparotomy in 20 mongrel dogs, a
      pediatric umbilical catheter was inserted into the CBD via a small cholecystotomy
      and attached to a water-perfused pressure transducer. After baseline CBD pressure
      readings, a lateral duodenotomy was performed. A total of 100 units of Botox was
      injected with an endoscopic sclerotherapy needle into all four quadrants of the
      ampulla. The dogs were randomly divided into four groups to undergo repeat
      laparotomy at either postoperative day 1 (group I), postoperative day 3 (group
      II), postoperative day 7 (group III), or postoperative day 14 (group IV). At the
      time of second laparotomy, a pressure-sensing catheter was reinserted into the
      CBD and pressures recorded. Each dog then underwent transpapillary biliary
      stenting with a 7 Fr. x 5 cm Cotton-Leung biliary stent and CBD pressures were
      again recorded. RESULTS: CBD pressures were significantly lower as compared with
      baseline for all groups after Botox injection and after biliary stenting (P
      <0.001) In addition, no significant differences in the degree of CBD pressure
      reduction were identified between groups I through IV after Botox injection. The
      measured decrease in CBD pressure from baseline after Botox injection as compared
      with biliary stenting was significantly different for groups I and II (P <0.05)
      but not for groups III and IV. CONCLUSION: Botox injection into the sphincter of
      Oddi results in significant CBD pressure reduction within 24 hours and continues
      for 14 days. Also, after postoperative day 3, there is no significant difference
      in the reduction of CBD pressure from baseline between Botox injection and
      biliary stenting. Based on these findings, Botox injection into the sphincter of
      Oddi may be a beneficial alternative to biliary stenting for the treatment of
      biliary leaks and fistulae.

PMID- 11248179
TI  - Differential diagnosis of polypoid lesions of the gallbladder by endoscopic
      ultrasonography.
AB  - BACKGROUND: Transabdominal ultrasonography (US) has made the detection of
      gallbladder polyps easier, but the differential diagnosis of polyps less than 20
      mm remains difficult. Therefore, we evaluated the usefulness of endoscopic
      ultrasonography (EUS) for the differential diagnosis of gallbladder polyps.
      METHODS: Among patients with gallbladder polyps less than 20 mm, we reviewed 89
      patients who underwent US and EUS before surgery and assessed the results of
      differential diagnoses by them. RESULTS: In all, 86.5% of these polyps were
      precisely diagnosed by EUS. However, only 51.7% were diagnosed by US.
      Sensitivity, specificity, and positive and negative predictive values of EUS at
      the diagnosis of carcinoma were 91.7%, 87.7%, 75.9%, and 96.6%, respectively.
      Those of US were 54.2%, 53.8%, 54.2%, and 94.6%, respectively. CONCLUSIONS: EUS
      may markedly improve the accuracy of the differential diagnosis of gallbladder
      polyps. Therefore, EUS is thought to play an important role in determining the
      treatment strategy for gallbladder polyps.

PMID- 11248180
TI  - Role of laparoscopic cholecystectomy in the management of gangrenous
      cholecystitis.
AB  - BACKGROUND: Laparoscopic cholecystectomy is increasingly being employed as the
      initial surgical approach in patients with acute cholecystitis. Gangrenous
      cholecystitis will be unexpectedly encountered in a proportion of these patients.
      The applicability of laparoscopic techniques and its outcome in this group of
      patients remain poorly defined. This paper presents our experience with
      laparoscopic cholecystectomy in the treatment of patients with gangrenous
      cholecystitis. METHODS: From January 1994 to March 1999, 281 patients underwent
      laparoscopic cholecystectomy for acute cholecystitis. Operative and
      histopathologic data were obtained and the subgroup with gangrenous cholecystitis
      identified (53 of 281, 18.8%). Laparoscopic cholecystectomy was the initial
      surgical approach in 44 (83%) and was successfully completed in 30 of 44 (68%)
      patients. Conversion to an open cholecystectomy became necessary in 14 of 44
      (32%). A retrospective review comparing these two groups of patients was
      performed. RESULTS: Of the 44 patients, there were 25 males and 19 females, with
      a mean age of 64.6 years. Mean duration of symptoms prior to presentation was 2.3
      and 2.9 days in the laparoscopic and conversion groups, respectively. Clinical
      presentation included the presence of right upper quadrant pain (98%),
      leukocytosis (91%), fever (16.3%), and jaundice (9%). Liver function test
      abnormalities included elevations of alkaline phosphatase (25%), aspartate
      aminotransferase (20.4%), alanine aminotransferase (22.7%), and total bilirubin
      (18.1%). Ultrasonography revealed the presence of gallstones (88.6%), gallbladder
      wall thickening (52.3%), and pericholecystic fluid (20.5%). Air in the
      gallbladder wall and intraluminal membranes were present in 2 patients and 1
      patient, respectively. Nuclear scans performed in 29 patients revealed cystic
      duct obstruction in all 29. The rim sign was present in 1 patient. A laparoscopic
      cholecystectomy was attempted in 44 of 53 patients and was successfully completed
      in 30 (68%). Conversion to an open procedure became necessary in 14 of 44 (32%).
      No difference in preoperative factors was noted among the two groups. The mean
      duration of surgery in patients undergoing a successful laparoscopic
      cholecystectomy was 107 minutes versus 110 minutes when conversion was necessary.
      There were no deaths in the study population. Morbidity occurred in 40% of the
      laparoscopic group and 71% of the conversion group. No patient in the
      laparoscopic group required admission to the intensive care unit. In contrast, 4
      of 14 patients in the conversion group required a mean of 2.6 days in the
      intensive care unit. Postoperative hospital stay was 3.3 versus 5.5 days in the
      two groups, respectively. CONCLUSIONS: Preoperative factors did not predict
      conversion in patients undergoing laparoscopic cholecystectomy for presumed acute
      cholecystitis who are found to have gangrenous cholecystitis. Duration of surgery
      is not significantly prolonged and outcome in terms of morbidity, admission to
      the intensive care unit, and hospital stay are significantly better in patients
      in whom laparoscopic cholecystectomy is successful.

PMID- 11248181
TI  - Measuring outcomes in surgical patients.
AB  - The current emphasis on quality of healthcare, cost effectiveness, and consumer
      satisfaction demands a better understanding of the relationship between the
      process of care and the outcomes of care. As patients become more active in
      defining healthcare quality, outcome measures are becoming increasingly patient
      focused. To meet these new demands for understanding the process-outcomes
      relationship, there exists a tremendous need for physician involvement in
      developing outcomes assessment programs. Such programs are best designed through
      the cooperative efforts of clinicians and outcomes statisticians. Advances in
      outcomes assessment will require a combination of increased precision in
      measurement, greater analysis of outliers, and the development of computerized
      repositories of clinical and health status data.

PMID- 11248182
TI  - Long-term outcome study of growth factor-treated pressure ulcers.
AB  - BACKGROUND: Exogenous application of growth factors have been reported in an
      attempt to accelerate healing of chronic wounds. Most of the trials were of brief
      duration with short to no follow-up periods. Long-term outcome studies are sparse
      for pressure ulcer therapies with success rates around 30% for both operative and
      nonoperative treatments. METHODS: Follow-up evaluations were performed serially
      up to 12 months for patients completing a 35 day blinded, placebo-controlled
      cytokine clinical trial of pressure ulcers. RESULTS: Fifty-four of 61 patients
      completed the follow-up period with 68.5% of the patients (37 of 54) being healed
      after 1 year. Of patients healing > or =85% during the active treatment phase,
      84.6% were healed after 1 year compared with 61% of those that healed <85% during
      treatment (P <0.05). CONCLUSION: Long-term outcome was better in this growth
      factor trial than with surgical or standard nonoperative treatment of pressure
      ulcers. Since only patients receiving exogenously applied cytokines achieved >85%
      closure during the treatment phase of the trial, the excellent long-term outcome
      appears attributable to the cytokine therapy.

PMID- 11248184
TI  - Coupling mechanism of the oxaloacetate decarboxylase Na(+) pump.
AB  - The oxaloacetate decarboxylase Na(+) pump consists of subunits alpha, beta and
      gamma, and contains biotin as the prosthetic group. The peripheral alpha subunit
      catalyzes the carboxyltransfer from oxaloacetate to the prosthetic biotin group
      to yield the carboxybiotin enzyme. Subsequently, this is decarboxylated in a
      Na(+)-dependent reaction by the membrane-bound beta subunit. The decarboxylation
      is coupled to Na(+) translocation from the cytoplasm into the periplasm, and
      consumes a periplasmically derived proton. The gamma subunit contains a Zn(2+)
      metal ion which may be involved in the carboxyltransfer reaction. It is proposed
      to insert with its N-terminal alpha-helix into the membrane and to form a complex
      with the alpha subunit with its water-soluble C-terminal domain. The beta subunit
      consists of nine transmembrane alpha-helices, a segment (IIIa) which inserts from
      the periplasm into the membrane but does not penetrate it, and connecting
      hydrophilic loops. The most highly conserved regions of the molecule are segment
      IIIa and transmembrane helix VIII. Functionally important residues are D203
      (segment IIIa), Y229 (helix IV) and N373, G377, S382 and R389 (helix VIII). The
      polar of these amino acids may constitute a network of ionizable groups which
      promotes the translocation of Na(+) and the oppositely oriented translocation of
      H(+) across the membrane. Evidence indicates that two Na(+) ions are bound
      simultaneously to subunit beta with D203 and S382 acting as binding sites. Sodium
      ion binding from the cytoplasm to both sites elicits decarboxylation of
      carboxybiotin possibly with the consumption of the proton extracted from S382 and
      delivered via Y229 to the carboxylated prosthetic group. A conformational change
      exposes the bound Na(+) ions toward the periplasm. With H(+) entering from the
      periplasm, the hydroxyl group of S382 is regenerated, and as a consequence, the
      Na(+) ions are released into this compartment. After switching back to the
      original conformation, Na(+) pumping continues.

PMID- 11248185
TI  - Sodium ion-translocating decarboxylases.
AB  - The review is concerned with three Na(+)-dependent biotin-containing
      decarboxylases, which catalyse the substitution of CO(2) by H(+) with retention
      of configuration (DeltaG degrees '=-30 kJ/mol): oxaloacetate decarboxylase from
      enterobacteria, methylmalonyl-CoA decarboxylase from Veillonella parvula and
      Propiogenium modestum, and glutaconyl-CoA decarboxylase from Acidaminococcus
      fermentans. The enzymes represent complexes of four functional domains or
      subunits, a carboxytransferase, a mobile alanine- and proline-rich biotin
      carrier, a 9-11 membrane-spanning helix-containing Na(+)-dependent carboxybiotin
      decarboxylase and a membrane anchor. In the first catalytic step the carboxyl
      group of the substrate is converted to a kinetically activated carboxylate in N
      carboxybiotin. After swing-over to the decarboxylase, an electrochemical Na(+)
      gradient is generated; the free energy of the decarboxylation is used to
      translocate 1-2 Na(+) from the inside to the outside, whereas the proton comes
      from the outside. At high [Na(+)], however, the decarboxylases appear to catalyse
      a mere Na(+)/Na(+) exchange. This finding has implications for the life of P.
      modestum in sea water, which relies on the synthesis of ATP via Delta(mu)Na(+)
      generated by decarboxylation. In many sequenced genomes from Bacteria and Archaea
      homologues of the carboxybiotin decarboxylase from A. fermentans with up to 80%
      sequence identity have been detected.

PMID- 11248186
TI  - The Na(+)-translocating methyltransferase complex from methanogenic archaea.
AB  - Methanogenic archaea are dependent on sodium ions for methane formation. A sodium
      ion-dependent step has been shown to be methyl transfer from N(5)
      methyltetrahydromethanopterin to coenzyme M. This exergonic reaction (DeltaG
      degrees '=-30 kJ/mol) is catalyzed by a Na(+)-translocating membrane-associated
      multienzyme complex composed of eight different subunits, MtrA-H. Subunit MtrA
      harbors a cob(I)amide prosthetic group which is methylated and demethylated in
      the catalytic cycle, demethylation being sodium ion-dependent. Based on the
      finding that in the cob(II)amide oxidation state the corrinoid is bound in a base
      off/His-on configuration it is proposed that methyl transfer from MtrA to
      coenzyme M is associated with a conformational change of the protein and that
      this change drives the electrogenic translocation of the sodium ions.

PMID- 11248187
TI  - Recent progress in the Na(+)-translocating NADH-quinone reductase from the marine
      Vibrio alginolyticus.
AB  - The respiratory chain of Gram-negative marine and halophilic bacteria has a Na(+)
      dependent NADH-quinone reductase that functions as a primary Na(+) pump. The
      Na(+)-translocating NADH-quinone reductase (NQR) from the marine Vibrio
      alginolyticus is composed of six structural genes (nqrA to nqrF). The NqrF
      subunit has non-covalently bound FAD. There are conflicting results on the
      existence of other flavin cofactors. Recent studies revealed that the NqrB and
      NqrC subunits have a covalently bound flavin, possibly FMN, which is attached to
      a specified threonine residue. A novel antibiotic, korormicin, was found to
      specifically inhibit the NQR complex. From the homology search of the nqr operon,
      it was found that the Na(+)-pumping NQR complex is widely distributed among Gram
      negative pathogenic bacteria.

PMID- 11248188
TI  - Na(+) translocation by bacterial NADH:quinone oxidoreductases: an extension to
      the complex-I family of primary redox pumps.
AB  - The current knowledge on the Na(+)-translocating NADH:ubiquinone oxidoreductase
      of the Na(+)-NQR type from Vibrio alginolyticus, and on Na(+) transport by the
      electrogenic NADH:Q oxidoreductases from Escherichia coli and Klebsiella
      pneumoniae (complex I, or NDH-I) is summarized. A general mode of redox-linked
      Na(+) transport by NADH:Q oxidoreductases is proposed that is based on the
      electrostatic attraction of a positively charged Na(+) towards a negatively
      charged, enzyme-bound ubisemiquinone anion in a medium of low dielectricity. A
      structural model of the [2Fe-2S]- and FAD-carrying NqrF subunit of the Na(+)-NQR
      from V. alginolyticus based on ferredoxin and ferredoxin:NADP(+) oxidoreductase
      suggests that a direct participation of the Fe/S center in Na(+) transport is
      rather unlikely. A ubisemiquinone-dependent mechanism of Na(+) translocation is
      proposed that results in the transport of two Na(+) ions per two electrons
      transferred. Whereas this stoichiometry of the pump is in accordance with in vivo
      determinations of Na(+) transport by the respiratory chain of V. alginolyticus,
      higher (Na(+) or H(+)) transport stoichiometries are expected for complex I,
      suggesting the presence of a second coupling site.

PMID- 11248189
TI  - Structure-function relationships of Na(+), K(+), ATP, or Mg(2+) binding and
      energy transduction in Na,K-ATPase.
AB  - The focus of this article is on progress in establishing structure-function
      relationships through site-directed mutagenesis and direct binding assay of
      Tl(+), Rb(+), K(+), Na(+), Mg(2+) or free ATP at equilibrium in Na,K-ATPase.
      Direct binding may identify residues coordinating cations in the E(2)[2K] or
      E(1)P[3Na] forms of the ping-pong reaction sequence and allow estimates of their
      contributions to the change of Gibbs free energy of binding. This is required to
      understand the molecular basis for the pronounced Na/K selectivity at the
      cytoplasmic and extracellular surfaces. Intramembrane Glu(327) in transmembrane
      segment M4, Glu(779) in M5, Asp(804) and Asp(808) in M6 are essential for tight
      binding of K(+) and Na(+). Asn(324) and Glu(327) in M4, Thr(774), Asn(776), and
      Glu(779) in 771-YTLTSNIPEITP of M5 contribute to Na(+)/K(+) selectivity. Free ATP
      binding identifies Arg(544) as essential for high affinity binding of ATP or ADP.
      In the 708-TGDGVND segment, mutations of Asp(710) or Asn(713) do not interfere
      with free ATP binding. Asp(710) is essential and Asn(713) is important for
      coordination of Mg(2+) in the E(1)P[3Na] complex, but they do not contribute to
      Mg(2+) binding in the E(2)P-ouabain complex. Transition to the E(2)P form
      involves a shift of Mg(2+) coordination away from Asp(710) and Asn(713) and the
      two residues become more important for hydrolysis of the acyl phosphate bond at
      Asp(369).

PMID- 11248190
TI  - Catalytic properties of Na(+)-translocating V-ATPase in Enterococcus hirae.
AB  - V-ATPases make up a family of proton pumps distributed widely from bacteria to
      higher organisms. We found a variant of this family, a Na(+)-translocating
      ATPase, in a Gram-positive bacterium, Enterococcus hirae. The Na(+)-ATPase was
      encoded by nine ntp genes from F to D in an ntp operon (ntpFIKECGABDHJ): the ntpJ
      gene encoded a K(+) transporter independent of the Na(+)-ATPase. Expression of
      this operon, encoding two transport systems for Na(+) and K(+) ions, was
      regulated at the transcriptional level by intracellular Na(+) as the signal.
      Structural aspects and catalytic properties of purified Na(+)-ATPase closely
      resembled those of other V-type H(+)-ATPases. Interestingly, the E. hirae enzyme
      showed a very high affinity for Na(+) at catalytic reaction. This property
      enabled the measurement of ion binding to this ATPase for the first time in the
      study of V- and F-ATPases. Properties of Na(+) binding to V-ATPase were
      consistent with the model that V-ATPase proteolipids form a rotor ring consisting
      of hexamers, each having one cation binding site. We propose here a structure
      model of Na(+) binding sites of the enzyme.

PMID- 11248191
TI  - Na(+)-driven flagellar motor of Vibrio.
AB  - Bacterial flagellar motors are molecular machines powered by the electrochemical
      potential gradient of specific ions across the membrane. Bacteria move using
      rotating helical flagellar filaments. The flagellar motor is located at the base
      of the filament and is buried in the cytoplasmic membrane. Flagellar motors are
      classified into two types according to the coupling ion: namely the H(+)-driven
      motor and the Na(+)-driven motor. Analysis of the flagellar motor at the
      molecular level is far more advanced in the H(+)-driven motor than in the Na(+)
      driven motor. Recently, the genes of the Na(+)-driven motor have been cloned from
      a marine bacterium of Vibrio sp. and some of the motor proteins have been
      purified and characterized. In this review, we summarize recent studies of the
      Na(+)-driven flagellar motor.

PMID- 11248192
TI  - The Na(+)-translocating F(1)F(0) ATP synthase of Propionigenium modestum:
      mechanochemical insights into the F(0) motor that drives ATP synthesis.
AB  - The ATP synthase of Propionigenium modestum encloses a rotary motor involved in
      the production of ATP from ADP and inorganic phosphate utilizing the free energy
      of an electrochemical Na(+) ion gradient. This enzyme clearly belongs to the
      family of F(1)F(0) ATP synthases and uses exclusively Na(+) ions as the
      physiological coupling ion. The motor domain, F(0), comprises subunit a and the b
      subunit dimer which are part of the stator and the subunit c oligomer acting as
      part of the rotor. During ATP synthesis, Na(+) translocation through F(0)
      proceeds from the periplasm via the stator channel (subunit a) onto a Na(+)
      binding site of the rotor (subunit c). Upon rotation of the subunit c oligomer
      versus subunit a, the occupied rotor site leaves the interface with the stator
      and the Na(+) ion can freely dissociate into the cytoplasm. Recent experiments
      demonstrate that the membrane potential is crucial for ATP synthesis under
      physiological conditions. These findings support the view that voltage generates
      torque in F(0), which drives the rotation of the gamma subunit thus liberating
      tightly bound ATP from the catalytic sites in F(1). We suggest a mechanochemical
      model for the transduction of transmembrane Na(+)-motive force into rotary torque
      by the F(0) motor that can account quantitatively for the experimental data.

PMID- 11248193
TI  - The Na(+) cycle in Acetobacterium woodii: identification and characterization of
      a Na(+) translocating F(1)F(0)-ATPase with a mixed oligomer of 8 and 16 kDa
      proteolipids.
AB  - The homoacetogenic bacterium Acetobacterium woodii relies on a sodium ion current
      across its cytoplasmic membrane for energy-dependent reactions. The sodium ion
      potential is established by a yet to be identified primary, electrogenic pump
      connected to the Wood-Ljungdahl pathway. Reactions possibly involved in Na(+)
      export are discussed. The electrochemical sodium ion potential generated is used
      to drive endergonic reactions such as flagellar rotation and ATP synthesis.
      Biochemical and molecular data identified the Na(+)-ATPase of A. woodii as a
      typical member of the F(1)F(0) class of ATPases. Its catalytic properties and the
      hypothetical sodium ion binding site in subunit c are discussed. The encoding
      genes were cloned and, surprisingly, the atp operon was shown to contain multiple
      copies of genes encoding subunit c. Two copies encode identical 8 kDa
      proteolipids, and a third copy arose by duplication and subsequent fusion of two
      genes. Furthermore, the duplicated subunit c does not contain the ion binding
      site in hair pin two. Biochemical and molecular data revealed that all three
      copies of subunit c constitute a mixed oligomer. The evolution of the structure
      and function of subunit c in ATPases from eucarya, bacteria, and archaea is
      discussed.

PMID- 11248194
TI  - Sodium-substrate cotransport in bacteria.
AB  - A variety of sodium-substrate cotransport systems are known in bacteria. Sodium
      enters the cell down an electrochemical concentration gradient. There is
      obligatory coupling between the entry of the ion and the entry of substrate with
      a stoichiometry (in the cases studied) of 1:1. Thus, the downhill movement of
      sodium ion into the cell leads to the accumulation of substrate within the cell.
      The melibiose carrier of Escherichia coli is perhaps the most carefully studied
      of the sodium cotransport systems in bacteria. This carrier is of special
      interest because it can also use protons or lithium ions for cotransport. Other
      sodium cotransport carriers that have been studied recently are for proline,
      glutamate, serine-threonine, citrate and branched chain amino acids.

PMID- 11248195
TI  - Towards the molecular mechanism of Na(+)/solute symport in prokaryotes.
AB  - The Na(+)/solute symporter family (SSF, TC No. 2.A.21) contains more than 40
      members of pro- and eukaryotic origin. Besides their sequence similarity, the
      transporters share the capability to utilize the free energy stored in
      electrochemical Na(+) gradients for the accumulation of solutes. As part of
      catabolic pathways most of the transporters are most probably involved in the
      acquisition of nutrients. Some transporters play a role in osmoadaptation. With a
      high resolution structure still missing, a combination of genetic, protein
      chemical and spectroscopic methods has been used to gain new insights into the
      structure and molecular mechanism of action of the transport proteins. The
      studies suggest a common 13-helix motif for all members of the SSF according to
      which the N-terminus is located in the periplasm and the C-terminus is directed
      into the cytoplasm (except for proteins containing a N- or C-terminal extension).
      Furthermore, an amino acid substitution analysis of the Na(+)/proline transporter
      (PutP) of Escherichia coli, a member of the SSF, has identified regions of
      particular functional importance. For example, amino acids of TM II of PutP
      proved to be critical for high affinity binding of Na(+) and proline. In
      addition, it was shown that ligand binding induces widespread conformational
      alterations in the transport protein. Taken together, the studies substantiate
      the common idea that Na(+)/solute symport is the result of a series of ligand
      induced structural changes.

PMID- 11248197
TI  - The Na(+)-dependence of alkaliphily in Bacillus.
AB  - A Na(+) cycle plays a central role in the remarkable capacity of aerobic,
      extremely alkaliphilic Bacillus species for pH homeostasis. The capacity for pH
      homeostasis, in turn, appears to set the upper pH limit for growth. One limb of
      the alkaliphile Na(+) cycle consists of Na(+)/H(+) antiporters that achieve net
      H(+) accumulation that is coupled to Na(+) efflux. The major antiporter on which
      pH homeostasis depends is thought to be the Mrp(Sha)-encoded antiporter, first
      identified from a partial clone in Bacillus halodurans C-125. Mrp(Sha) may
      function as a complex. While this antiporter is capable of secondary antiport
      energized by an imposed or respiration-generated protonmotive force, the
      possibility of a primary mode has not been excluded. In Bacillus pseudofirmus
      OF4, at least two additional antiporters, including NhaC, have supporting roles
      in pH homeostasis. Some of these additional antiporters may be especially
      important for antiport at low [Na(+)] or at near-neutral pH. The second limb of
      the Na(+) cycle facilitates Na(+) re-entry via Na(+)/solute symporters and,
      perhaps, the ion channel associated with the Na(+)-dependent flagellar motor. The
      process of pH homeostasis is also enhanced, perhaps especially during transitions
      to high pH, by different arrays of secondary cell wall polymers in the two
      alkaliphilic Bacillus species studied most intensively. The mechanisms whereby
      alkaliphiles handle the challenge of Na(+) stress at very elevated [Na(+)] are
      just beginning to be identified, and a hypothesis has been advanced to explain
      the finding that B. pseudofirmus OF4 requires a higher [Na(+)] for growth at near
      neutral pH than at very alkaline pH values.

PMID- 11248196
TI  - Na(+)/H(+) antiporters.
AB  - Na(+)/H(+) antiporters are membrane proteins that play a major role in pH and
      Na(+) homeostasis of cells throughout the biological kingdom, from bacteria to
      humans and higher plants. The emerging genomic sequence projects already have
      started to reveal that the Na(+)/H(+) antiporters cluster in several families.
      Structure and function studies of a purified antiporter protein have as yet been
      conducted mainly with NhaA, the key Na(+)/H(+) antiporter of Escherichia coli.
      This antiporter has been overexpressed, purified and reconstituted in a
      functional form in proteoliposomes. It has recently been crystallized in both 3D
      as well as 2D crystals. The NhaA 2D crystals were analyzed by cryoelectron
      microscopy and a density map at 4 A resolution was obtained and a 3D map was
      reconstructed. NhaA is shown to exist in the 2D crystals as a dimer of monomers
      each composed of 12 transmembrane segments with an asymmetric helix packing. This
      is the first insight into the structure of a polytopic membrane protein. Many
      Na(+)/H(+) antiporters are characterized by very dramatic sensitivity to pH, a
      property that corroborates their role in pH homeostasis. The molecular mechanism
      underlying this pH sensitivity has been studied in NhaA. Amino acid residues
      involved in the pH response have been identified. Conformational changes
      transducing the pH change into a change in activity were found in loop VIII-IX
      and at the N-terminus by probing trypsin digestion or binding of a specific
      monoclonal antibody respectively. Regulation by pH of the eukaryotic Na(+)/H(+)
      antiporters involves an intricate signal transduction pathway (recently reviewed
      by Yun et al., Am. J. Physiol. 269 (1995) G1-G11). The transcription of NhaA has
      been shown to be regulated by a novel Na(+)-specific regulatory network. It is
      envisaged that interdisciplinary approaches combining structure, molecular and
      cell biology as well as genomics should be applied in the future to the study of
      this important group of transporters.

PMID- 11248198
TI  - Role of sodium bioenergetics in Vibrio cholerae.
AB  - The ability of the bacterium to use sodium in bioenergetic processes appears to
      play a key role in both the environmental and pathogenic phases of Vibrio
      cholerae. Aquatic environments, including fresh, brackish, and coastal waters,
      are an important factor in the transmission of cholera and an autochthonous
      source. The organism is considered to be halophilic and has a strict requirement
      for Na(+) for growth. Furthermore, expression of motility and virulence factors
      of V. cholerae is intimately linked to sodium bioenergetics and to each other.
      Several lines of evidence indicated that the activity of the flagellum of V.
      cholerae might have an impact on virulence gene regulation. As the V. cholerae
      flagellum is sodium-driven and the Na(+)-NQR enzyme is known to create a sodium
      motive force across the bacterial membrane, it was recently suggested that the
      increased toxT expression observed in a nqr-negative strain is mediated by
      affecting flagella activity. It was suggested that the V. cholerae flagellum
      might respond to changes in membrane potential and the resulting changes in
      flagellar rotation might serve as a signal for virulence gene expression.
      However, we recently demonstrated that although the flagellum of V. cholerae is
      not required for the effects of ionophores on virulence gene expression, changes
      in the sodium chemical potential are sensed and thus alternative mechanisms,
      perhaps involving the TcpP/H proteins, for the detection of these conditions must
      exist. Analyzing the underlying mechanisms by which bacteria respond to changes
      in the environment, such as their ability to monitor the level of membrane
      potential, will probably reveal complex interplays between basic physiological
      processes and virulence factor expression in a variety of pathogenic species.

PMID- 11248199
TI  - Stoichiometry of cholesterol-sphingomyelin condensed complexes in monolayers.
AB  - Some binary mixtures of cholesterol and phospholipids in monolayers have
      thermodynamic phase diagrams with two upper miscibility critical points. This
      feature has been interpreted in terms of 'condensed complexes' between the
      phospholipid and cholesterol. The present work gives evidence for the formation
      of complexes with a common simple integral stoichiometry in binary mixtures of
      cholesterol and a series of five sphingomyelins where the amide-linked acyl chain
      length is varied. This indicates that these complexes have a distinct geometry
      even though they form a liquid phase.

PMID- 11248200
TI  - Characterization of bile acid transport mediated by multidrug resistance
      associated protein 2 and bile salt export pump.
AB  - Biliary excretion of certain bile acids is mediated by multidrug resistance
      associated protein 2 (Mrp2) and the bile salt export pump (Bsep). In the present
      study, the transport properties of several bile acids were characterized in
      canalicular membrane vesicles (CMVs) isolated from Sprague--Dawley (SD) rats and
      Eisai hyperbilirubinemic rats (EHBR) whose Mrp2 function is hereditarily
      defective and in membrane vesicles isolated from Sf9 cells infected with
      recombinant baculovirus containing cDNAs encoding Mrp2 and Bsep. ATP-dependent
      uptake of [(3)H]taurochenodeoxycholate sulfate (TCDC-S) (K(m)=8.8 microM) and
      [(3)H]taurolithocholate sulfate (TLC-S) (K(m)=1.5 microM) was observed in CMVs
      from SD rats, but not from EHBR. In addition, ATP-dependent uptake of [(3)H]TLC-S
      (K(m)=3.9 microM) and [(3)H]taurocholate (TC) (K(m)=7.5 microM) was also observed
      in Mrp2- and Bsep-expressing Sf9 membrane vesicles, respectively. TCDC-S and TLC
      S inhibited the ATP-dependent TC uptake into CMVs from SD rats with IC(50) values
      of 4.6 microM and 1.2 microM, respectively. In contrast, the corresponding values
      for Sf9 cells expressing Bsep were 59 and 62 microM, respectively, which were
      similar to those determined in CMVs from EHBR (68 and 33 microM, respectively).
      By co-expressing Mrp2 with Bsep in Sf9 cells, IC(50) values for membrane vesicles
      from these cells shifted to values comparable with those in CMVs from SD rats
      (4.6 and 1.2 microM). Moreover, in membrane vesicles where both Mrp2 and Bsep are
      co-expressed, preincubation with the sulfated bile acids potentiated their
      inhibitory effect on Bsep-mediated TC transport. These results can be accounted
      for by assuming that the sulfated bile acids trans-inhibit the Bsep-mediated
      transport of TC.

PMID- 11248201
TI  - Human intestinal anion exchanger isoforms: expression, distribution, and membrane
      localization.
AB  - A family of anion exchangers (AEs) including AE1, AE2 and AE3 has been described.
      AE3 gene has been shown to encode two alternatively spliced isoforms termed as
      bAE3 (brain subtype) and cAE3 (cardiac subtype). The identity of the AE(s)
      involved in the human intestinal NaCl absorption is not fully understood. Current
      studies were undertaken to identify the AE isoforms expressed in the human
      intestine, to define their regional and vertical axis (crypt vs. surface cells)
      distribution, and to elucidate their membrane localization in the epithelial
      cells along the entire length of the human intestine. Our studies utilizing
      reverse transcription (RT)-PCR with total RNA extracted from pinch biopsies from
      various regions of the human intestine demonstrate that AE2 and bAE3 but not AE1
      or cAE3 were expressed in all the regions of the human intestine. Utilizing in
      situ RT-PCR, we demonstrated that the message of AE2 was expressed throughout the
      vertical surface--crypt axis of the colon. Our Western blotting studies
      demonstrated that AE2 and bAE3 are localized to the basolateral but not the
      apical membranes of the intestinal epithelial cells from the human ileum and
      colon. In conclusion, our results demonstrated that in the human intestine, AE2
      and bAE3, but not AE1 or cAE3, are expressed throughout the tract with the
      highest expression in the colon compared to the ileum and jejunum. Both the
      isoforms were found to be localized to the basolateral but not the apical
      membranes of the epithelial cells. We speculate that, in the human intestine, AE2
      and bAE3 may be the 'housekeeping' isoforms, and the apical AE, the potential
      candidate for chloride absorption, remains to be identified.

PMID- 11248203
TI  - Application of the transition state theory to water transport across cell
      membranes.
AB  - We have applied the transition state theory of Eyring et al. (The Theory of Rate
      Processes, McGraw-Hill, 1941) to water transport across cell membranes. We have
      then evaluated free energy (Delta F(not equal)), enthalpy (Delta H(not equal))
      and entropy (Delta S(not equal)) of activation for water permeation across
      membranes, such as Arbacia eggs, Xenopus oocytes with or without aquaporin water
      channels, mammalian erythrocytes, aquaporin proteoliposomes, liposomes and
      collodion membrane. Delta H(not equal) was found to be correlated with Delta
      S(not equal). This is so-called Delta H(not equal) and Delta S(not equal)
      compensation over the ranges of Delta H(not equal) and Delta S(not equal) from 2
      to 22 kcal/mol and from -26 to 45 e.u., respectively, indicating that low Delta
      H(not equal) values correspond to negative Delta S(not equal). Large positive
      Delta S(not equal) and high Delta H(not equal) values might be accompanied by
      reversible breakage of secondary bonds in the membrane, presumably in membrane
      lipid bilayer. Largely negative Delta S(not equal) and low Delta H(not equal)
      values for aquaporin water channels, aquaporin proteoliposomes and porous
      collodion membrane could be explained by the immobilization of permeating water
      molecules in the membrane, i.e., the partial loss of rotational and/or
      translational freedoms of water molecules in water channels.

PMID- 11248202
TI  - Effect of magainin, class L, and class A amphipathic peptides on fatty acid spin
      labels in lipid bilayers.
AB  - Magainins and other antimicrobial peptides increase ion flux across the membrane.
      They may do this by forming some type of pore or by perturbing lipid organization
      due to peptide lying on the bilayer surface. In order to determine if magainins
      perturb the lipid sufficiently to permeabilize the bilayer, their effect on the
      motion of fatty acid and lipid spin labels in
      phosphatidylcholine/phosphatidylglycerol (PC/PG) lipid vesicles was determined.
      Their effect was compared to two synthetic peptides, 18L and Ac-18A-NH(2),
      designed to mimic the naturally occurring classes of lytic (class L) and
      apolipoprotein (class A) amphipathic helices, respectively. We show that although
      magainins and 18L both had significant effects on lipid chain order, much greater
      than Ac-18A-NH(2), there was no correlation between these effects and the
      relative ability of these three peptide classes to permeabilize PC/PG vesicles in
      the order magainins=Ac-18A-NH(2) >> 18L. This suggests that the perturbing
      effects of magainins on lipid chain order at permeabilizing concentrations are
      not directly responsible for the increased leakage of vesicle contents. The
      greater ability of the magainins to permeabilize PC/PG vesicles relative to 18L
      is thus more likely due to formation of some type of pore by magainins. The
      greater ability of Ac-18A-NH(2) relative to 18L to permeabilize PC/PG vesicles
      despite its lack of disordering effect must be due to its ability to cause
      membrane fragmentation. Effects of these peptides on other lipids indicated that
      the mechanism by which they permeabilize lipid bilayers depends both on the
      peptide and on the lipid composition of the vesicles.

PMID- 11248204
TI  - Neutron reflection from a dimyristoylphosphatidylcholine monolayer adsorbed on a
      hydrophobised silicon support.
AB  - Neutron specular reflection has been used to study the structure of a monolayer
      of dimyristoylphosphatidylcholine (DMPC) deposited using the Langmuir-Blodgett
      technique onto a silicon oxide substrate. A self-assembled monolayer of
      octadecyltrichlorosilane with a deuterated alkyl chain (d-OTS) had been
      previously bonded onto this silicon oxide substrate which rendered it
      hydrophobic. In the system under study, the alkyl chains of the phospholipid were
      found to penetrate extensively into the d-OTS layer with the mixed chain region
      (d-OTS and DMPC) having a total thickness of 30.5 A. This mixed region was
      divided into two halves for analysis; the 'lower half' (nearest to the substrate
      surface) was found to comprise anchored d-OTS chains mixed with the lipid chains
      in the volume ratio approx. 0.60:0.35. The corresponding volume ratio in the
      'upper half' of this region was determined to be approx. 0.50:0.40. The
      thicknesses of these regions were found to be 17.9 A (incorporating approx. 6%
      solvent) and 12.6 A (incorporating approx. 9% solvent) for the lower and upper
      halves respectively. The DMPC head groups were found to be confined to the most
      external layer (furthest away from the silicon substrate). This layer was found
      to have a thickness of 9.4 A and included a small fraction of the lipid alkyl
      chains with approx. 47% solvent.

PMID- 11248205
TI  - Differential scanning calorimetry and (2)H nuclear magnetic resonance and Fourier
      transform infrared spectroscopy studies of the effects of transmembrane alpha
      helical peptides on the organization of phosphatidylcholine bilayers.
AB  - We have studied the effects of the incorporation of the alpha-helical
      transmembrane peptides Ac-K(2)-L(24)-K(2)-amide (L(24)) and Ac-K(2)-(L-A)(12)
      K(2)-amide ((LA)(12)) on the thermotropic phase behavior of 1,2-dipalmitoyl-d(62)
      sn-glycero-3-phosphocholine (DPPC-d(62)) and 1-palmitoyl-d(31)-2-oleoyl-sn
      glycero-3-phosphocholine (POPC-d(31)) lipid bilayer model membranes by
      differential scanning calorimetry (DSC) and the conformational and orientational
      order of the phospholipid chains by Fourier transform infrared (FTIR)
      spectroscopy and (2)H nuclear magnetic resonance ((2)H-NMR) spectroscopy,
      respectively. Our DSC and FTIR spectroscopic studies indicate that the peptides
      L(24) and (LA)(12) both decrease the temperature and enthalpy of the gel/liquid
      crystalline phase transition of DPPC-d(62) bilayers, with (LA)(12) having the
      greater effect in this regard. An examination of the frequencies of the CH(2) and
      CD(2) symmetric stretching bands of the infrared spectra of liquid-crystalline
      states of the peptide-free and peptide-containing DPPC-d(62) and POPC-d(31)
      samples, and a comparison with the orientational order as measured by (2)H-NMR
      spectroscopy as well as with the chain order as measured by electron spin
      resonance spectroscopy, lead us to conclude that the CH(2) (or CD(2)) stretching
      frequencies of lipid hydrocarbon chains are not a reliable measure of chain
      conformational order in lipid bilayers containing significant amounts of peptides
      or other lipophilic inclusions. In contrast, the results of our (2)H-NMR
      spectroscopic studies present a consistent picture in which both L(24) and
      (LA)(12) increased in a similar way the time-averaged orientational order of the
      lipid chains of their liquid-crystalline lipid bilayer hosts. The comparison of
      the effects L(24) and (LA)(12) on phosphatidylcholine bilayers indicates that the
      gel-to-liquid-crystalline phase transition appears to be more sensitive to small
      changes in transmembrane peptide surface topology than hydrocarbon carbon chain
      orientational order in the liquid-crystalline state.

PMID- 11248206
TI  - Factors underlying membrane potential-dependent and -independent fluorescence
      responses of potentiometric dyes in stressed cells: diS-C(3)(3) in yeast.
AB  - The redistribution fluorescent dye diS-C(3)(3) responds to yeast plasma membrane
      depolarisation or hyperpolarisation by Delta psi-dependent outflow from or uptake
      into the cells, reflected in changes in the fluorescence maximum lambda(max) and
      fluorescence intensity. Upon membrane permeabilisation the dye redistributes
      between the cell and the medium in a purely concentration-dependent manner, which
      gives rise to Delta psi-independent fluorescence responses that may mimic Delta
      psi-dependent blue or red shift in lambda(max). These lambda(max) shifts after
      cell permeabilisation depend on probe and ion concentrations inside and outside
      the cells at the moment of permeabilisation and reflect (a) permeabilisation
      induced Delta psi collapse, (b) changing probe binding capacity of cell
      constituents (inverse to the ambient ionic strength) and (c) hampering of probe
      equilibration by the poorly permeable cell wall. At low external ion
      concentrations, cell permeabilisation causes ion outflow and probe influx
      (hyperpolarisation-like red shift in lambda(max)) caused by an increase in the
      probe-binding capacity of the cell interior and, in the case of heat shock,
      protein denaturation unmasking additional probe-binding sites. At high external
      ion levels minimising net ion efflux and at high intracellular probe
      concentrations at the moment of permeabilisation, the Delta psi collapse causes a
      blue lambda(max) shift mimicking an apparent depolarisation.

PMID- 11248207
TI  - Topology of the Na(+)/dicarboxylate cotransporter: the N-terminus and hydrophilic
      loop 4 are located intracellularly.
AB  - The current secondary structure model of the Na(+)/dicarboxylate cotransporter,
      NaDC-1, contains 11 transmembrane domains. The model is based on hydropathy
      analysis and the extracellular location of the carboxy terminus, which contains
      an N-glycosylation site. In this study, the model was further tested using
      indirect immunofluorescence of COS-7 cells. The Flag epitope tag (DYKDDDDK) was
      fused to the amino terminus of NaDC-1 (Flag-NaDC-1), and a monoclonal antibody
      against the Flag epitope was used to determine the location of the N-terminus.
      Hydrophilic loop 4 of NaDC-1 was identified using polyclonal antibodies raised
      against a fusion protein containing amino acids 164--233 of NaDC-1. The
      expression of NaDC-1 and Flag-NaDC-1 in COS-7 cells was confirmed by functional
      assays of succinate transport and by Western blots of cell surface biotinylated
      proteins. Immunofluorescent labeling of cells expressing both NaDC-1 and Flag
      NaDC-1 required permeabilization of the plasma membranes with digitonin whereas
      no immunofluorescence was visible in intact cells. The results of this study show
      that both the N-terminus and hydrophilic loop 4 of NaDC-1 are located
      intracellularly, which supports the current model of NaDC-1 structure.

PMID- 11248208
TI  - Spectrophotometric analysis of organisation of dipalmitoylphosphatidylcholine
      bilayers containing the polyene antibiotic amphotericin B.
AB  - Amphotericin B (AmB) is a polyene antibiotic widely used in the treatment of deep
      seated fungal infections. The mode of action of AmB is directly related to the
      effect of the drug on the lipid phase of biomembranes. In the present work the
      effect of AmB on the properties of lipid bilayers formed with
      dipalmitoylphosphatidylcholine (DPPC) and the effect of the lipid phase on the
      molecular organisation of AmB were studied with application of spectrophotometry
      in the UV-Vis region. The absorption spectra of AmB in lipid membranes display a
      complex structure with hypsochromically and bathochromically shifted bands
      indicative of formation of molecular aggregates of the drug. Formation of
      molecular aggregates was analysed at different concentrations of the drug in the
      lipid phase in the range 0.05--5 mol% and at different temperatures in the range
      5--55 degrees C. The aggregation level of AmB in the ordered phase of DPPC
      displayed a minimum corresponding to a concentration of 1 mol% with respect to
      the lipid. An increase in the aggregation level was observed in the temperature
      region corresponding to the main phase transition. The structure of molecular
      aggregates of AmB is analysed on the basis of spectroscopic effects in terms of
      the exciton splitting model. Analysis of the position of the absorption maximum
      of AmB in the lipid phase of DPPC in terms of the theory of solvatochromc effects
      makes it possible to ascribe the refractive indices n=1.40 and n=1.49 to the
      hydrophobic core of the membrane in the L(alpha) and the P(beta)' phase
      respectively. Analysis of the aggregation of AmB in the lipid phase in relation
      to the physical state of the membrane reveals that the temperature range of the
      main phase transition of a lipid cluster in the immediate vicinity of AmB depends
      on its concentration. The termination of the phase transition temperature, as
      read from the AmB aggregation, varies between 42 degrees C at 1 mol% AmB in DPPC
      and 49 degrees C at 5 mol% AmB in DPPC. The exciton splitting theory applied to
      the analysis of the spectroscopic data makes it possible to calculate the
      diameter of the AmB pore as 2.8 A in the gel phase and 3.6 A in the fluid phase
      of the DPPC membrane, on the assumption that the pore is formed by nine AmB
      molecules.

PMID- 11248209
TI  - Secondary structure in lung surfactant SP-B peptides: IR and CD studies of bulk
      and monolayer phases.
AB  - Pulmonary surfactant protein SP-B is known to facilitate adsorption and spreading
      of surfactant components across the air/water interface. This property appears
      essential for in vivo function in the alveolar subphase and at the air/alveolar
      surface. Three peptides with amino acid sequences based on SP-B containing
      predicted alpha-helical regions (SP-B(1--20), SP-B(9--36A), SP-B(40--60A)) have
      been synthesized to probe structure-function relationships and protein-lipid
      interaction in bulk phase and monolayer environments. IR and CD studies are
      reported along with traditional surface pressure-molecular area (pi-A) isotherms
      and IR reflection-absorption spectroscopy (IRRAS) investigations conducted at the
      air/water interface. In bulk phase, helix-promoting environments (methanol and
      aqueous dispersions of lipid vesicles), SP-B(1--20) and SP-B(9--36A) contained
      significant amounts of alpha-helical structure, whereas varying degrees of alpha
      helix, random coil, and beta-sheet were observed in aqueous solutions and
      monolayers. The most striking behavior was observed for SP-B(9--36A), which
      displayed reversible surface pressure-induced beta-sheet formation. Bulk phase
      lipid melting curves and monolayer experiments with peptide-lipid mixtures showed
      subtle differences in the degree of bulk phase interaction and substantial
      differences in peptide surface activity. The uniqueness of IRRAS is emphasized as
      the importance of evaluating secondary structure in both bulk phase and monolayer
      environments for lung surfactant peptide mimics is demonstrated.

PMID- 11248210
TI  - Photoinitiated destabilization of sterically stabilized liposomes.
AB  - A considerable effort has been devoted to the development of liposomes for the
      transport and buffering of drugs in the body. Several research groups have
      reported the increased localization of sterically stabilized liposomes (PEG
      liposomes) at tumor sites. If PEG-liposomes are to be effective carriers of
      therapeutic agents, their drug permeability must be sufficiently low that little
      passive release occurs during the circulation time of the PEG-liposomes. However,
      once PEG-liposomes reach tumor sites, it may be desirable to accelerate the
      release of the encapsulated drug. The use of light to stimulate the release of
      encapsulated compounds from liposomes is attractive, because it is possible to
      control the spatial and temporal delivery of the radiation. PEG-liposomes
      composed in part of the photosensitive lipid, bis-SorbPC, can be prepared in a
      manner that effectively encapsulates water soluble compounds, yet releases them
      upon exposure to ultraviolet light in the presence of oxygen. The observed
      increase in liposome permeability is about 200-fold at high photoconversion of
      the monomeric bis-SorbPC. The increase in permeability is dependent on the extent
      of photolysis, but independent of both the charge on the PEG-lipid and the mole
      fraction of PEG-lipid included in the liposome. Therefore the photoinitiated
      destabilization of these PEG-liposomes is not a consequence of micellization of
      the PEG-lipid, but probably due to the formation of defects in the bilayer during
      crosslinking of the bis-SorbPC. The photoinduced increase in liposome
      permeability is great enough to make it possible to release therapeutic agents
      from PEG-liposomes at specific sites in a manner of tens of minutes to hours.

PMID- 11248211
TI  - Adenosine and adenosine triphosphate modulate the substrate binding affinity of
      glucose transporter GLUT1 in vitro.
AB  - Evidence indicates that a large portion of the facilitative glucose transporter
      isoform GLUT1 in certain animal cells is kept inactive and activated in response
      to acute metabolic stresses. A reversible interaction of a certain inhibitor
      molecule with GLUT1 protein has been implicated in this process. In an effort to
      identify this putative GLUT1 inhibitor molecule, we studied here the effects of
      adenosine and adenosine triphosphate (ATP) on the binding of D-glucose to GLUT1
      by assessing their abilities to displace cytochalasin B (CB), using purified
      GLUT1 in vesicles. At pH 7.4, adenosine competitively inhibited CB binding to
      GLUT1 and also reduced the substrate binding affinity by more than an order of
      magnitude, both with an apparent dissociation constant (K(D)) of 3.0 mM. ATP had
      no effect on CB and D-glucose binding to GLUT1, but reduced adenosine binding
      affinity to GLUT1 by 2-fold with a K(D) of 30 mM. At pH 3.6, however, ATP
      inhibited the CB binding nearly competitively, and increased the substrate
      binding affinity by 4--5-fold, both with an apparent K(D) of 1.22 mM. These
      findings clearly demonstrate that adenosine and ATP interact with GLUT1 in vitro
      and modulate its substrate binding affinity. They also suggest that adenosine and
      ATP may regulate GLUT1 intrinsic activity in certain cells where adenosine
      reduces the substrate-binding affinity while ATP increases the substrate-binding
      affinity by interfering with the adenosine effect and/or by enhancing the
      substrate-binding affinity at an acidic compartment.

PMID- 11248212
TI  - Involvement of serum mannan binding proteins and mannose receptors in uptake of
      mannosylated liposomes by macrophages.
AB  - The roles of serum mannan binding protein (MBP) and the mannose receptor in the
      cellular uptake of mannosylated liposomes (Man-liposomes) by macrophages were
      studied. Man-liposomes were prepared by incorporating cholesten-5-yloxy-N-(4-((1
      imino-2-beta-D-thiomannosylethyl)amino)butyl)formamide (Man-C4-Chol) into small
      unilamellar long circulating liposomes consisting of cholesterol (Chol) and
      distearoyl phosphatidylcholine (DSPC). In the in vitro cellular uptake study with
      cultured mouse peritoneal macrophages, [(3)H]Man-liposomes were taken up to a
      great extent, whereas no significant uptake was observed for [(3)H]cholesterol
      and DSPC liposomes without Man-C4-Chol (Bare-liposomes). The uptake of [(3)H]Man
      liposomes was dose- and temperature-dependent and inhibited by an excess of
      mannosylated bovine serum albumin, suggesting their specific uptake via membrane
      mannose receptor-mediated endocytosis. Furthermore, it was demonstrated that
      (111)In-MBP binds strongly to Man-liposomes based on the recognition of Man-C4
      Chol and markedly enhanced their uptake by macrophages. These results are
      supported by confocal laser microscopic images. In addition, in vivo hepatic
      uptake of (111)In-MBP was enhanced by Man-liposomes. On the other hand, the
      uptake of Man-liposomes was significantly reduced by preincubation with serum and
      further with MBP-depleted serum suggesting inhibitory effects of serum proteins
      such as albumin on mannose receptor-mediated endocytosis. The involvement of
      serum-type MBP and membrane mannose receptors in the uptake of Man-liposomes is
      thus suggested.

PMID- 11248213
TI  - Effect of cholesterol on interaction of dibucaine with phospholipid vesicles: a
      fluorescence study.
AB  - Interaction of the local anesthetic dibucaine with small unilamellar vesicles of
      dimyristoylphosphatidylcholine (DMPC) and dioleoyl phosphatidylcholine (DOPC)
      containing different mol percents of cholesterol has been studied by fluorescence
      spectroscopy. Fluorescence measurements on dibucaine in presence of phospholipid
      vesicles containing various amounts of cholesterol yielded a pattern of variation
      of wavelength at emission maximum and steady-state anisotropy which indicated
      that the microenvironment of dibucaine is more polar and flexible in membranes
      that contain cholesterol than in membranes without cholesterol. Experiments on
      quenching of fluorescence from membrane-associated dibucaine by potassium iodide
      showed a marked increase in quenching efficiency as the cholesterol content of
      the vesicles was increased, demonstrating increased accessibility of the iodide
      quenchers to dibucaine in the presence of cholesterol, when compared to that in
      its absence. Total emission intensity decay profiles of dibucaine yielded two
      lifetime components of approximately 1 ns and approximately 2.8--3.1 ns with mean
      relative contributions of approximately 25 and approximately 75%, respectively.
      The mean lifetime in vesicles was 20--30% smaller than in the aqueous medium and
      showed a moderate variation with cholesterol content. Fluorescence measurements
      at two different temperatures in DMPC SUVs, one at 33 degrees C, above the phase
      transition temperature and another at 25 degrees C, around the main phase
      transition, indicated two different mode of dibucaine localization. At 25 degrees
      C dibucaine partitioned differentially in presence and absence of cholesterol.
      However, at 33 degrees C the apparent partition coefficients remained unaltered
      indicating differences in the microenvironment of dibucaine in presence and
      absence of cholesterol in the phospholipid membranes.

PMID- 11248214
TI  - Molecular dynamics simulations of stratum corneum lipid models: fatty acids and
      cholesterol.
AB  - We report the results of an investigation on stratum corneum lipids, which
      present the main barrier of the skin. Molecular dynamics simulations, thermal
      analysis and FTIR measurements were applied. The primary objective of this work
      was to study the effect of cholesterol on skin structure and dynamics. Two
      molecular models were constructed, a free fatty acid bilayer (stearic acid,
      palmitic acid) and a fatty acid/cholesterol mixture at a 1:1 molar ratio. Our
      simulations were performed at constant pressure and temperature on a nanosecond
      time scale. The resulting model structures were characterized by calculating
      surface areas per headgroup, conformational properties, atom densities and order
      parameters of the fatty acids. Analysis of the simulations indicates that the
      free fatty acid fraction of stratum corneum lipids stays in a highly ordered
      crystalline state at skin temperatures. The phase behavior is strongly influenced
      when cholesterol is added. Cholesterol smoothes the rigid phases of the fatty
      acids: the order of the hydrocarbon tails (mainly of the last eight bonds) is
      reduced, the area per molecule becomes larger, the fraction of trans dihedrals is
      lower and the hydrophobic thickness is reduced. The simulation results are in
      good agreement with our experimental data from FTIR analysis and NIR-FT Raman
      spectroscopy.

PMID- 11248215
TI  - Characterization of immunoglobulin binding to isolated human erythrocyte
      membranes: evidence for selective, temperature-induced binding of naturally
      occurring autoantibodies to the cytoskeleton.
AB  - Human plasma contains naturally occurring autoantibodies to the predominant
      components of the erythrocyte membrane: band 3 and spectrin bands 1 and 2 of the
      cytoskeleton. The titer of cytoskeletal plasma autoantibodies increases in
      various hemolytic conditions, suggesting that opsonization of the cytoskeleton
      may play an important role in the clearance of hemolyzed (not senescent)
      erythrocytes from the circulation. In this study, we use Alexa Fluor 488 goat
      anti-human IgG conjugate (Molecular Probes, Eugene, OR, USA), to characterize
      plasma immunoglobulin binding to erythrocyte membranes from osmotically hemolyzed
      cells ('ghosts'). The results show that exposure of ghosts to plasma results in 4
      fold more immunoglobulin binding to the cytoskeleton than is bound to the
      proteins contained within the lipid bilayer. Preincubation of the ghosts at 37
      degrees C causes 8-fold more immunoglobulin binding to the cytoskeleton compared
      to bilayer proteins. This temperature-induced change resulted from selective
      immunoglobulin binding to the cytoskeleton, with no change in immunoglobulin
      binding to bilayer proteins. However, the rate of increase in cytoskeletal
      antigenicity at 37 degrees C did correlate with the rate of a conformational
      change in band 3, a transmembrane protein which serves as a major membrane
      attachment site for the cytoskeleton. The results of this study suggest that the
      cytoskeleton is the primary target in the opsonization of hemolyzed erythrocyte
      membranes by naturally occurring plasma autoantibodies. The conformational
      changes which occur in ghosts at 37 degrees C are associated with selective
      exposure of new immunoglobulin binding sites on the cytoskeleton, and with a
      change in the structure of band 3. We propose a model suggesting that
      opsonization of the cytoskeleton occurs prior to the decomposition of hemolyzed
      erythrocytes at 37 degrees C.

PMID- 11248216
TI  - Molecular and functional characterization of sodium--hydrogen exchanger in skin
      as well as cultured keratinocytes and melanocytes.
AB  - The sodium--hydrogen (Na(+)/H(+)) exchanger is one of the few transporter
      proteins involved in the regulation and maintenance of intracellular pH and cell
      volume in most eukaryotic cell types. The current study investigates the
      expression of isoforms of the Na(+)/H(+) exchanger (NHE) in human skin and in
      cultured keratinocytes, melanocytes, and melanoma cells by reverse transcription
      polymerase chain reaction (RT--PCR), immunohistochemical analysis and functional
      studies. Neonatal foreskins were used to isolate RNA from epidermis and dermis,
      and to initiate cultures of keratinocytes and melanocytes. RT--PCR on RNA
      isolated from epidermis, dermis, keratinocytes, melanocytes and melanoma cells
      using PCR primers specific for NHE-1 yielded a 463 bp PCR product. RT--PCR
      performed using primers specific for NHE isoforms 2, 3, 4 and 5 did not yield any
      products. Western blotting analysis (of keratinocyte and melanocyte cell
      cultures) and indirect immunohistochemistry on neonatal foreskin, keratinocytes,
      melanocytes and melanoma cells using a NHE-1-specific polyclonal antibody
      demonstrated NHE-1 expression at the protein level. Physiological regulation of
      intracellular pH using a pH-sensitive dye, BCECF, detected an amiloride-sensitive
      NHE activity in human keratinocyte, melanocyte and melanoma cell cultures. These
      results indicate that cultures of human keratinocytes and melanocytes established
      from human skin and melanoma cells express the NHE-1 isoform of the sodium-
      hydrogen exchanger.

PMID- 11248217
TI  - Molecular cloning of Na(+)-ATPase cDNA from a marine alga, Heterosigma akashiwo.
AB  - We cloned novel Na(+)-ATPase (HANA) cDNA from marine alga Heterosigma akashiwo.
      The full-length HANA cDNA was 4467 bp long and coded for a 1330 amino acid
      protein with a molecular weight of 146,306. The deduced product exhibited around
      40% identity in amino acids with Na(+)/K(+)-ATPase alpha-subunits. A hydrophilic
      sequence of 285 amino acid residues that showed no homology with any sequence
      listed in databases existed in the M7--M8 junction of HANA. This is the first
      report on the primary structure of putative Na(+)-transporting ATPase from plant
      cells.

PMID- 11248218
TI  - Protective effect of various antioxidants on the toxicity of sulphur mustard
      administered to mice by inhalation or percutaneous routes.
AB  - Protective effect of various antioxidants, trolox (water soluble analogue of
      vitamin E), quercetin (bioflavonoid) and glutathione reduced (GSH), was studied
      following sulphur mustard (SM) intoxication. SM, a blistering agent was
      administered to Swiss albino female mice through inhalation (1 LC50=42.3 mg/m3
      for 1 h duration; 14 days observation for mortality) and percutaneous (1
      LD50=154.7 mg/kg; 7 days observation for mortality) routes. The antioxidants were
      administered three times at the dose of trolox, 500 microg/kg; quercetin, 5 mg/kg
      and GSH, 400 mg/kg body weight by intraperitoneal injection, one immediately
      following SM exposure, then once each day for 2 days after SM treatment. The
      effect of antioxidants on survival, markers of oxidative damage and purine
      metabolites was investigated. Survival study animals were observed for 14 days.
      Oxidative markers (in blood, liver and lung) and purine metabolites (in blood and
      urine) were investigated 72 h after SM treatment. Survival time increased
      significantly following trolox and quercetin treatments through the inhalation
      route. Significant decrease in GSH and increase in the level of malondialdehyde
      (MDA) indicated oxidative damage to liver and lung tissues following SM
      inhalation and percutaneous exposure. Blood and urinary uric acid, end product of
      purine metabolism showed an increased following both routes of exposures. The
      antioxidants, trolox and quercetin protected the liver and lung tissues from
      oxidative damage caused by SM exposure through inhalation and percutaneous
      routes. This study showed that antioxidants could enhance survival time, protect
      liver and lung from oxidative damage and reduce accumulation of purine
      metabolites in blood following SM intoxication.

PMID- 11248219
TI  - Inactivation of creatine kinase during the interaction of indomethacin with
      horseradish peroxidase and hydrogen peroxide: involvement of indomethacin
      radicals.
AB  - Creatine kinase (CK) was used as a marker molecule to examine the side effect of
      damage to tissues by indomethacin (IM), an effective drug to treat rheumatoid
      arthritis and gout, with horseradish peroxidase and hydrogen peroxide (HRP-H2O2).
      IM inactivated CK during its interaction with HRP-H2O2. Under aerobic conditions,
      inactivation of CK significantly decreased. CK in rat heart homogenate was also
      inactivated by IM with HRP-H2O2. When IM was incubated with HRP-H2O2, the maximum
      absorption of IM at 280 nm rapidly decreased and a new peak at 410 nm occurred
      with isosbestic points at 260 and 312 nm. In contrast, under anaerobic
      conditions, the spectral change of IM was almost absent, indicating IM was
      oxidized to the yellow substance by HRP-H2O2. Adding catalase strongly inhibited
      the production of yellow substance. Sodium azide also blocked the formation of
      yellow substance and the inactivation of CK. Electron spin resonance signals of
      IM carbon-centered radical were detected using 2-methyl-2-nitrosopropane during
      the interaction of IM with HRP-H2O2 under anaerobic conditions. Oxygen was
      consumed during the interaction of IM with HRP-H2O2. These results suggest that
      IM carbon-centered radicals may rapidly react with O2 to generate the peroxyl
      radicals. Sulfhydryl groups and tryptophane residues of CK decreased during the
      interaction of IM with HRP-H2O2. Other sulfhydryl enzymes, including alcohol
      dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase, were also readily
      inactivated during the interaction with HRP-H2O2. Sulfhydryl enzymes seem to be
      very sensitive to IM activated by HRP-H2O2.

PMID- 11248220
TI  - Antiproliferative activity and interactions with cell-cycle related proteins of
      the organotin compound triethyltin(IV)lupinylsulfide hydrochloride.
AB  - Organotin compounds, particularly tri-organotin, have demonstrated cytotoxic
      properties against a number of tumor cell lines. On this basis,
      triethyltin(IV)lupinylsulfide hydrochloride (IST-FS 29), a quinolizidine
      derivative, was synthesized and developed as a potential antitumor agent. This
      tin-derived compound exhibited potent antiproliferative effects on three
      different human cancer cell lines: teratocarcinoma of the ovary (PA-1), colon
      carcinoma (HCT-8) and glioblastoma (A-172). Cytotoxic activity was assessed by
      MTT and cell count assays during time course experiments with cell recovery after
      compound withdrawal. Significant cell growth inhibition (up to 95% in HCT-8 after
      72 h of exposure), which also persisted after drug-free medium change, was
      reported in all the cell lines by both assays. In addition, the cytocidal effects
      exerted by IST-FS 29 appeared more consistent with necrosis or delayed cell
      death, rather than apoptosis, as shown by morphologic observations under light
      microscope, DNA fragmentation analysis and flow cytometry. In the attempt to
      elucidate whether this compound might affect genes playing a role in G1/S phase
      transition, the expressions of p53, p21(WAF1), cyclin D1 and Rb, mainly involved
      in response to DNA-damaging stress, were analyzed by Western blot. Heterogeneous
      patterns of expression during exposure to IST-FS 29 were evidenced in the
      different cell lines suggesting that these cell-cycle-related genes are not
      likely the primary targets of this compound. Thus, the present data seem more
      indicative of a direct effect of IST-FS-29 on macromolecular synthesis and
      cellular homeostasis, as previously hypothesized for other organotin complexes.

PMID- 11248221
TI  - Stereospecificity in membrane effects of catechins.
AB  - Green tea catechins consisting of catechin stereoisomers and their derivatives
      have been suggested to show biological activities through the interactions with
      cellular membranes. Their effects on membrane fluidity were comparatively studied
      by measuring fluorescence polarization of liposomal membranes prepared with
      phospholipids and cholesterol. All catechin stereoisomers reduced membrane
      fluidity by acting on the hydrophilic and hydrophobic regions of membrane
      bilayers at 20-500 microM. Both epicatechins in a cis form were more effective
      for reducing membrane fluidity than both catechins in a trans form. (-)
      Epicatechin, (+)-epicatechin, (-)-catechin and (+)-catechin reduced membrane
      fluidity in increasing order of intensity. Such difference between optical
      isomers was increased by chiral cholesterol added to membrane lipids. In reversed
      phase chromatographic evaluation, (-)-epicatechin and (+)-epicatechin were more
      hydrophobic than (-)-catechin and (+)-catechin, although hydrophobicity was not
      distinguishable between optical isomers. Stereospecificity in the membrane
      effects of catechin stereoisomers may be induced by the different hydrophobicity
      of geometrical isomers and the chirality of membrane lipid components. At lower
      concentrations (5-100 microM), (-)-epigallocatechin gallate and (-)-epicatechin
      gallate reduced membrane fluidity more significantly than (-)-epicatechin,
      suggesting that the intensive membrane effect contributes to the potent medicinal
      utility of (-)-epigallocatechin gallate.

PMID- 11248222
TI  - Characterization of metabolic activation of pentachlorophenol to quinones and
      semiquinones in rodent liver.
AB  - Pentachlorophenol (PCP), a widely used biocide, induces liver tumors in mice but
      not in rats. Metabolic activation of PCP to chlorinated quinones and semiquinones
      in liver cytosol from Sprague-Dawley rats and B6C3F1 mice was investigated in
      vitro (1) with microsomes in the presence of either beta-nicotinamide adenine
      dinucleotide phosphate (NADPH) or cumene hydroperoxide (CHP), (2) with CHP in the
      absence of microsomes, and (3) with horseradish peroxidase (HRP) and H2O2. Mono-S
      and multi-S-substituted adducts of tetrachloro-1,4-benzoquinone (Cl4-1,4-BQ) and
      Cl4-1,2-BQ and their corresponding semiquinones [i.e. tetrachloro-1,4
      benzosemiquinone (Cl4-1,4-SQ) and tetrachloro-1,2-benzosemiquinone (Cl4-1,2-SQ)]
      were measured by gas chromatography-mass spectrometry (GC-MS). Qualitatively, the
      metabolites of PCP were the same in both rats and mice for all activation
      systems. Induction of PCP metabolism by either 3MC or PB-treated microsomes was
      observed in NADPH- but not in CHP-supported systems. In rats, the amount of
      induction was comparable with either 3MC or PB. 3MC was a stronger inducer than
      PB in mice and also induced a greater amount of metabolism than in rats. This
      suggests that induction of specific P450 isozymes may play a role in the toxicity
      of PCP to mice. Both HRP/H2O2 and CHP led to production of the full spectrum of
      chlorinated quinones and semiquinones, confirming the direct oxidation of PCP.
      CHP (with or without microsomes) converted PCP into much greater quantities of
      quinones and semiquinones than did microsomal P450/NADPH or HRP/H2O2 in both
      species. This implies that, under conditions of oxidative stress, endogenous
      lipid hydroperoxides may increase PCP metabolism sufficiently to enhance the
      toxicity and carcinogenicity of PCP.

PMID- 11248224
TI  - Effects of modulation of tissue activities of DT-diaphorase on the toxicity of
      2,3-dimethyl-1,4-naphthoquinone to rats.
AB  - The enzyme DT-diaphorase mediates the two-electron reduction of quinones to
      hydroquinones. It has previously been shown that the toxicity of 2-methyl-1,4
      naphthoquinone to rats is decreased by pre-treatment of the animals with
      compounds that increase tissue levels of this enzyme. In contrast, the severity
      of the haemolytic anaemia induced in rats by 2-hydroxy-1,4-naphthoquinone was
      increased in animals with high levels of DT-diaphorase. In the present
      experiments, the effect of alterations in tissue diaphorase activities on the
      toxicity of a third naphthoquinone derivative, 2,3-dimethyl-1,4-naphthoquinone,
      has been investigated. This compound induced severe haemolysis and slight renal
      tubular necrosis in control rats. Pre-treatment of the animals with BHA, a potent
      inducer of DT-diaphorase, diminished the severity of the haemolysis induced by
      this compound and abolished its nephrotoxicity. Pre-treatment with dicoumarol, an
      inhibitor of this enzyme, caused only a slight increase in the haemolysis induced
      by 2,3-dimethyl-1,4-naphthoquinone, but provoked a massive increase in its
      nephrotoxicity. Modulation of DT-diaphorase activity in animals may therefore not
      only alter the severity of naphthoquinone toxicity, but also cause pronounced
      changes in the site of toxic action of these substances. The factors that may
      control whether induction of DT-diaphorase in animals will decrease or increase
      naphthoquinone toxicity are discussed.

PMID- 11248223
TI  - Responses of thiols to an oxidant challenge: differences between blood and
      tissues in the rat.
AB  - Treatment of rats with diamide (100 mg/kg i.p.) altered the thiol components of
      the blood to a very different extent than in tissues (liver, kidney, lung,
      spleen, heart and testis). A total consumption (10 min) and regeneration (120
      min) of blood glutathione (GSH), matched by a parallel increase and decrease in
      glutathione-protein mixed disulfides (GS-SP) was observed. In contrast, no
      modification of non-protein SH groups (NPSH) and protein SH groups (PSH), GS-SP
      and malondialdehyde (MDA) was observed in liver, kidney, lung, testis spleen and
      heart within same time range. In particular, only glutathione disulfide (GSSG)
      levels and some activities of antioxidant enzymes were modified to a small extent
      and in an opposite direction in some organs. For example, GSSG, and glucose-6
      phosphate dehydrogenase (G-6-PDH) and catalase (CAT) activities appeared up
      regulated in one tissue and down-regulated in another. The least modified organ
      was the liver, whereas lung and spleen were the most affected (lung, GSSG,
      significantly increased whereas G-6-PDH, glutaredoxin (GRX), GPX, superoxide
      dimutase (SOD) levels were significantly lowered; spleen, GSSG and the activity
      of glutathione reductase (GR), G-6-PDH and glutathione transferase (GST) were
      significantly decreased). The different responses of erythrocytes and organs to
      diamide were explained by the high affinity of hemoglobin and by the relatively
      high potential of thiol regeneration in organs. The rapid reversibility of the
      process of protein S-thiolation in blood and the small effects in organs leads us
      to propose the existence of an inter-organ cooperation in the rat that regulates
      protein S-thiolation in blood. Plasma thiols may well play a role in this
      process.

PMID- 11248225
TI  - Melatonin reduces interleukin secretion in amyloid-beta stressed mouse brain
      slices.
AB  - Neurodegeneration in Alzheimer's disease (AD) is associated with many features of
      the immune system. For example, cytokines such as IL-6, synthesized by microglia
      and astrocytes, are associated with senile plaques. To further study the role of
      cytokines in early stage AD neurodegeneration, an organotypic mouse brain slice
      culture system with microglia and astrocytes was developed. Amyloid-beta(Abeta1
      40) induced the secretion of both IL-1beta and IL-6. Melatonin, an antioxidant
      and pineal hormone, reduced interleukin secretion in a concentration dependent
      manner. We also observed that melatonin, alone, had no effect on IL-1beta
      secretion but at a concentration of 500 microM induced the secretion of IL-6.
      This organotypic slice system can be used to study the early role of immune
      system molecules on neurodegeneration.

PMID- 11248226
TI  - NAD(P)(+) decomposition and antioxidant defense of the cell.

PMID- 11248227
TI  - Pathophysiological relevance of mitochondria in NAD(+) metabolism.
AB  - Pyridine nucleotides are mostly stored within mitochondria where they are
      involved in different functions ranging from energy metabolism to cellular
      signaling. Here we discuss the mechanisms of mitochondrial NAD(+) metabolism and
      release that may contribute to the crucial roles played by these organelles as
      triggers or amplifiers of physiological and pathological events.

PMID- 11248228
TI  - Mitochondria, aging and longevity--a new perspective.
AB  - A new perspective is emerging indicating that mitochondria play a critical role
      in aging not only because they are the major source and the most proximal target
      of reactive oxygen species, but also because they regulate stress response and
      apoptosis. Recent literature indicates that, in response to stress, a variety of
      molecules translocate to and localise in mitochondria. These molecules are likely
      to interact with each other, in order to mediate mitochondria/nucleus cross-talk
      and to regulate apoptosis. We surmise that an integration of signals in
      multimolecular complexes occurs at mitochondrial level. These phenomena can be of
      critical importance for human aging and longevity.

PMID- 11248229
TI  - Molecular organization of the human serotonin transporter at the air/water
      interface.
AB  - The serotonin transporter (SERT) is the target of several important
      antidepressant and psychostimulant drugs. It has been shown that under defined
      conditions, the transporter spread at the air/water interface was able to bind
      its specific ligands. In this paper, the interfacial organization of the protein
      has been assessed from dynamic surface pressure and ellipsometric measurements.
      For areas comprising between 10,400 and 7,100 A(2)/molecule, ellipsometric
      measurements reveal an important change in the thickness of the SERT film. This
      change was attributed to the reorientation of the transporter molecules from a
      horizontal to their natural predictive transmembrane orientation. The thickness
      of the SERT film at 7,100 A(2)/molecule was found to be approximately equal to 84
      A and coincided well with the theoretical value estimated from the calculations
      based on the dimensions of alpha-helices containing membrane proteins. These data
      suggest that the three-dimensional arrangement of the SERT may be represented as
      a box with lengths d(z)=83--85 A and d(y) or d(x)=41--47 A.

PMID- 11248230
TI  - Expression levels of RGS7 and RGS4 proteins determine the mode of regulation of
      the G protein-activated K(+) channel and control regulation of RGS7 by G beta 5.
AB  - Regulators of G protein signaling RGS4 and RGS7 accelerate the kinetics of K(+)
      channels (GIRKs) in the Xenopus oocyte system. Here, via quantitative analysis of
      RGS expression, we reveal biphasic effects of RGSs on GIRK regulation. At low
      concentrations, RGS4 inhibited basal GIRK activity, but stimulated it at high
      concentrations. RGS7, which is associated with the G protein subunit G beta 5, is
      regulated by G beta 5 by two distinct mechanisms. First, G beta 5 augments RGS7
      activity, and second, it increases its expression. These dual effects resolve
      previous controversies regarding RGS4 and RGS7 function and indicate that they
      modulate signaling by mechanisms supplementary to their GTPase-activating protein
      activity.

PMID- 11248231
TI  - ESR studies on reaction of saccharide with the free radicals generated from the
      xanthine oxidase/hypoxanthine system containing iron.
AB  - The free radicals generated from the iron containing system of xanthine oxidase
      and hypoxanthine (Fe-XO/HX) were directly detected by using spin trapping. It was
      found that not only superoxide anion (O(2)*-) and hydroxyl radical (OH*), but
      also alkyl or alkoxyl radicals (R*) were formed when saccharides such as glucose,
      fructose and sucrose were added into the Fe-XO/HX system. The generated amount of
      R* was dependent on the kind and concentration of saccharides added into the Fe
      XO/HX system and no R* were detected in the absence of saccharides, indicating
      that there is an interaction between the saccharide molecules and the free
      radicals generated from the Fe-XO/HX system and saccharide molecules are
      essential for generating R* in the Fe-XO/HX system. It is expected that the
      toxicity of R* would be greater than of hydrophilic O(2)*- and OH* because they
      are liposoluble and their lives are longer and the active sites of biomolecules
      are closely related with lipophilic phase, thus they can damage cells more
      seriously than O(2)*- and OH*. The R* generated from the saccharide containing Fe
      XO/HX can be effectively scavenged by selenium containing abzyme (Se-abzyme),
      indicating Se-abzyme is a promising antioxidant.

PMID- 11248232
TI  - ctr1, a gene involved in a signal transduction pathway of the gliding motility in
      the cyanobacterium Synechocystis sp. PCC 6803.
AB  - We generated random Tn5 mutations in Synechocystis sp. PCC 6803 in search for
      genes involved in the signal transduction cascade for the cyanobacterial gliding
      motility. One of the non-gliding Tn5 mutants, S1-105, had an insertional
      inactivation in the slr1044 gene encoding a putative methyl-accepting chemotaxis
      protein. Interposon mutation on the slr1044 (named ctr1) in the bacterium also
      eliminated gliding motility. In the interposon mutant, the expression of pilA1
      was 5-fold decreased compared with that of wild-type and thick pili, that are
      believed to be the motor for gliding, could not be observed by an electron
      microscope. Therefore, we suggest that the Ctr1 protein functions as a transducer
      that regulates the expression of pilA1, and thus is required for the biogenesis
      of thick pili.

PMID- 11248233
TI  - Protein kinase C mu selectively activates the mitogen-activated protein kinase
      (MAPK) p42 pathway.
AB  - Here we show that human protein kinase C mu (PKC mu) activates the mitogen
      activated protein kinase (MAPK). Transient expression of constitutive active PKC
      mu leads to an activation of Raf-1 kinase as demonstrated by in vitro
      phosphorylation of MAPK. PKC mu enhances transcriptional activity of a basal
      thymidine kinase promotor containing serum response elements (SREs) as shown by
      luciferase reporter gene assays. SRE driven gene activation by PKC mu is
      triggered by the Elk-1 ternary complex factor. PKC mu-mediated activation of SRE
      driven transcription can be inhibited by the MEK1 inhibitor PD98059. In contrast
      to the activation of the p42/ERK1 MAPK cascade, transient expression of
      constitutive active PKC mu does neither affect c-jun N-terminal kinase nor p38
      MAPK.

PMID- 11248234
TI  - Expression and mutagenesis of the NqrC subunit of the NQR respiratory Na(+) pump
      from Vibrio cholerae with covalently attached FMN.
AB  - The Na(+)-translocating NADH:quinone oxidoreductase (Na(+)-NQR) is present in the
      membranes of a number of marine bacteria and pathogenic bacteria. Two of the six
      subunits of the Na(+)-NQR, NqrB and NqrC, have been previously shown to contain
      covalently bound flavin adenine mononucleotide (FMN). In the current work, the
      cloning of nqrC from Vibrio cholerae is reported. The gene has been expressed in
      V. cholerae and shown to contain one equivalent of covalently bound FMN. In
      contrast, no covalent flavin was detected when threonine-225 was replaced by
      leucine. The data show that the FMN attachment does not require assembly of the
      enzyme and are consistent with the unusual threonine attachment site.

PMID- 11248235
TI  - Direct observation of two distinct affinity conformations in the T state human
      deoxyhemoglobin.
AB  - The main features of cooperative oxygenation of human hemoglobin have been
      described by assuming the equilibrium between two affinity conformations of the
      entire molecule, T and R. However, the molecular basis for explaining the wide
      variation in the O(2) affinities of the deoxy T state has remained obscure. We
      address this long-standing issue by trapping the conformational states of
      deoxyhemoglobin molecules within wet porous transparent silicate sol-gels. The
      equilibrium O(2) binding measurements of the encapsulated deoxyhemoglobin samples
      showed that deoxyhemoglobin free of anions coexists in two conformations that
      differ in O(2) affinity by 40 times or more, and addition of inositol
      hexaphosphate to this anion-free deoxyhemoglobin brings about a very slow
      redistribution of these affinity conformations. These results are the first,
      direct demonstration of the existence of equilibrium between two (at least two)
      functionally distinguishable conformational states in the T state
      deoxyhemoglobin.

PMID- 11248237
TI  - Heterodimer formation between thioredoxin f and fructose 1,6-bisphosphatase from
      spinach chloroplasts.
AB  - Chloroplast fructose 1,6-bisphosphatase (FBPase) is activated by reduction of a
      regulatory disulfide through thioredoxin f (Trx f). In the course of this
      reduction a transient mixed disulfide is formed linking covalently Trx f with
      FBPase, which possesses three Cys on a loop structure, two of them forming the
      redox-active disulfide bridge. The goal of this study was to identify the Cys
      involved in the transient mixed disulfide. To stabilize this reaction
      intermediate, mutant proteins with modified active sites were used. We identified
      Cys-155 of the FBPase as the one engaged in the formation of the mixed disulfide
      intermediate with Cys-46 of Trx f.

PMID- 11248236
TI  - Pigment conformation and pigment-protein interactions in the reconstituted Lhcb4
      antenna protein.
AB  - Resonance Raman spectra of the native Lhcb4 antenna protein are compared with
      those of a recombinant protein prepared by in vitro refolding of its polypeptide,
      over-expressed in Escherichia coli, with added pigments [Giuffra et al. (1996)
      Eur. J. Biochem. 238, 112-120]. The results indicate that the native pigment
      conformation is reproduced almost perfectly in the reconstituted protein, with
      only small differences which are attributed to a slight shift in the Soret
      absorption peak of two or more chlorophylls. This procedure therefore represents
      a model system for the investigation of site-directed mutant LHC proteins, which
      are otherwise very difficult to obtain.

PMID- 11248238
TI  - Lactoferricin B causes depolarization of the cytoplasmic membrane of Escherichia
      coli ATCC 25922 and fusion of negatively charged liposomes.
AB  - Antimicrobial peptides have been extensively studied in order to elucidate their
      mode of action. Most of these peptides have been shown to exert a bactericidal
      effect on the cytoplasmic membrane of bacteria. Lactoferricin is an antimicrobial
      peptide with a net positive charge and an amphipatic structure. In this study we
      examine the effect of bovine lactoferricin (lactoferricin B; Lfcin B) on
      bacterial membranes. We show that Lfcin B neither lyses bacteria, nor causes a
      major leakage from liposomes. Lfcin B depolarizes the membrane of susceptible
      bacteria, and induces fusion of negatively charged liposomes. Hence, Lfcin B may
      have additional targets responsible for the antibacterial effect.

PMID- 11248239
TI  - Characterization and functional analysis of the nucleotide binding fold in human
      peroxisomal ATP binding cassette transporters.
AB  - The 70-kDa peroxisomal membrane protein (PMP70) and the adrenoleukodystrophy
      protein (ALDP) are half ATP binding cassette (ABC) transporters in the peroxisome
      membrane. Mutations in the ALD gene encoding ALDP result in the X-linked
      neurodegenerative disorder adrenoleukodystrophy. Plausible models exist to show a
      role for ATP hydrolysis in peroxisomal ABC transporter functions. Here, we
      describe the first measurements of the rate of ATP binding and hydrolysis by
      purified nucleotide binding fold (NBF) fusion proteins of PMP70 and ALDP. Both
      proteins act as an ATP specific binding subunit releasing ADP after ATP
      hydrolysis; they did not exhibit GTPase activity. Mutations in conserved residues
      of the nucleotidases (PMP70: G478R, S572I; ALDP: G512S, S606L) altered ATPase
      activity. Furthermore, our results indicate that these mutations do not influence
      homodimerization or heterodimerization of ALDP or PMP70. The study provides
      evidence that peroxisomal ABC transporters utilize ATP to become a functional
      transporter.

PMID- 11248240
TI  - Homing markers for atherosclerosis: applications for drug delivery, gene delivery
      and vascular imaging.
AB  - Endothelial dysfunction plays a major role in the pathogenesis of
      atherosclerosis. Pro-inflammatory cytokines such as interleukin-1 beta and tumour
      necrosis factor alpha activate endothelial cells changing their resting phenotype
      to become pro-adhesive, pro-thrombotic and pro-atherogenic. Phage display in vivo
      biopanning has been used to identify peptide sequences that home to diseased
      regions of the vessel wall in low density lipoprotein receptor (LDLr) knockout
      mice. In LDLr knockout mice, peptide sequence determinants exhibiting organ
      specificity have been isolated. These sequences have applications for gene
      delivery, drug delivery and for improving contrast agents for vascular imaging.

PMID- 11248241
TI  - Osmosensitivity of an inwardly rectifying chloride current revealed by whole-cell
      and perforated-patch recordings in cultured rat cortical astrocytes.
AB  - The osmosensitivity of the inwardly rectifying Cl(-) current (I(Clh)), expressed
      by primary cultured rat neocortical astrocytes long-term treated with dibutyryl
      cyclic AMP, was investigated in the whole-cell and perforated-patch modes. In
      whole-cell experiments, whereas hypotonic extracellular solution (Delta=100
      mOsmol) did not cause any change in I(Clh), hypertonicity produced a slowly
      developing, approximately 40% reversible decrease in current magnitude. By
      contrast, in perforated-patch experiments, exposure to a less hypertonic saline
      (Delta=50 mOsmol) depressed the current to approximately 50%, and hypotonicity
      induced a approximately 50% slow increase in I(Clh). These differences in
      osmosensitivity between the two experimental modes suggest that the
      osmoregulation of I(Clh) may be mediated by complex intracellular mechanism(s),
      which appear(s) to be partly compromised by the dialysis of the astrocytic
      cytoplasm.

PMID- 11248242
TI  - Characterization of TASK-4, a novel member of the pH-sensitive, two-pore domain
      potassium channel family.
AB  - We report the primary sequence of TASK-4, a novel member of the acid-sensitive
      subfamily of tandem pore K(+) channels. TASK-4 transcripts are widely expressed
      in humans, with highest levels in liver, lung, pancreas, placenta, aorta and
      heart. In Xenopus oocytes TASK-4 generated K(+) currents displaying a marked
      outward rectification which was lost by elevation of extracellular K(+). TASK-4
      currents were efficiently blocked by barium (83% inhibition at 2 mM), only weakly
      inhibited by 1 mM concentrations of quinine, bupivacaine and lidocaine, but not
      blocked by tetraethylammonium, 4-aminopyridine and Cs(+). TASK-4 was sensitive to
      extracellular pH, but in contrast to other TASK channels, pH sensitivity was
      shifted to more alkaline pH. Thus, TASK-4 in concert with other TASK channels
      might regulate cellular membrane potential over a wide range of extracellular pH.

PMID- 11248243
TI  - Oncostatin M and hepatocyte growth factor induce hepatic maturation via distinct
      signaling pathways.
AB  - Liver development is regulated by soluble factors as well as cell-cell contacts.
      We previously reported that oncostatin M (OSM) induced hepatic maturation in a
      primary culture of embryonic day 14 liver cells. While OSM expression in the
      liver starts in mid gestation and decreases in postnatal stages, hepatocyte
      growth factor (HGF) is mainly expressed in the liver in the first few days after
      birth. In this study, we compared the effect of OSM and HGF on the
      differentiation of fetal hepatic cells in vitro. Like OSM, HGF in the presence of
      dexamethasone induced expression of glucose-6-phosphatase, tyrosine amino
      transferase and carbamoyl-phosphate synthase, and accumulation of glycogen in
      fetal hepatic cells, although to a lesser extent than OSM. Interestingly, while
      both OSM and HGF up-regulated production of albumin, secretion of albumin
      occurred only in response to OSM. In addition, although hepatic maturation
      induced by OSM depends on STAT3, HGF failed to activate STAT3 and HGF-induced
      differentiation was independent of STAT3. These results indicate that OSM and HGF
      induce hepatic maturation through different signaling pathways.

PMID- 11248244
TI  - Characterization of recombinant human nicotinamide mononucleotide adenylyl
      transferase (NMNAT), a nuclear enzyme essential for NAD synthesis.
AB  - Nicotinamide mononucleotide adenylyl transferase (NMNAT) is an essential enzyme
      in all organisms, because it catalyzes a key step of NAD synthesis. However,
      little is known about the structure and regulation of this enzyme. In this study
      we established the primary structure of human NMNAT. The human sequence
      represents the first report of the primary structure of this enzyme for an
      organism higher than yeast. The enzyme was purified from human placenta and
      internal peptide sequences determined. Analysis of human DNA sequence data then
      permitted the cloning of a cDNA encoding this enzyme. Recombinant NMNAT exhibited
      catalytic properties similar to the originally purified enzyme. Human NMNAT
      (molecular weight 31932) consists of 279 amino acids and exhibits substantial
      structural differences to the enzymes from lower organisms. A putative nuclear
      localization signal was confirmed by immunofluorescence studies. NMNAT strongly
      inhibited recombinant human poly(ADP-ribose) polymerase 1, however, NMNAT was not
      modified by poly(ADP-ribose). NMNAT appears to be a substrate of nuclear kinases
      and contains at least three potential phosphorylation sites. Endogenous and
      recombinant NMNAT were phosphorylated in nuclear extracts in the presence of
      [gamma-(32)P]ATP. We propose that NMNAT's activity or interaction with nuclear
      proteins are likely to be modulated by phosphorylation.

PMID- 11248245
TI  - A redistribution of actin and myosin IIA accompanies Ca(2+)-dependent insulin
      secretion.
AB  - The study addressed the functional link between remodelling of the actomyosin
      cytoskeleton in pancreatic beta-cells and the regulation of insulin secretion.
      Confocal microscopy revealed that myosin heavy chain (MHC) IIA co-localized very
      well with filamentous (F)-actin in RINm5F cells but MHCIIB did not. Subcellular
      localization of MHCIIB was not altered by stimulation with 30 mM KCl (which
      evokes Ca(2+)-dependent insulin secretion). In contrast MHCIIA redistributed in a
      manner similar to F-actin, especially towards the apical surface, but also away
      from peripheral regions towards cell contact points on the basal surface.
      Finally, Ca(2+)-dependent insulin secretion was inhibited by stabilization of
      actin filaments with jasplakinolide. The results support a role for the
      MHCIIA/actin cytoskeleton in regulating insulin secretion.

PMID- 11248246
TI  - Mutations in the fatty acid elongation 1 gene are associated with a loss of beta
      ketoacyl-CoA synthase activity in low erucic acid rapeseed.
AB  - Low erucic acid rapeseed (LEAR) is characterised by a near absence of very long
      chain fatty acids in the seed oil which has been correlated with a lack of acyl
      CoA elongation activity. Here we show that the absence of acyl-CoA and ATP
      dependent elongation activities in microsomes isolated from LEAR embryos is
      associated with an absence of beta-ketoacyl-CoA synthase activity encoded by the
      Bn-fatty acid elongation 1 (FAE1) genes. Size exclusion chromatography of
      solubilised microsomes revealed the presence of a high molecular mass acyl-CoA
      elongase complex in high erucic acid rapeseed which was absent in microsomes
      isolated from LEAR seeds. Although transcripts for the Bn-FAE1 genes were
      detected in LEAR embryos, immunoblots using antisera raised against the beta
      ketoacyl-CoA synthase indicated an absence of this protein. Comparison of the
      deduced amino acid sequences of immature embryo cDNAs reveals that LEAR alleles
      of Bn-FAE1 encode variant beta-ketoacyl-CoA synthase proteins.

PMID- 11248247
TI  - Mutations in the basic domain and the loop-helix II junction of TWIST abolish DNA
      binding in Saethre-Chotzen syndrome.
AB  - Saethre-Chotzen syndrome is an autosomal dominant skull disorder resulting from
      premature fusion of coronal sutures (craniosynostosis). It is caused by mutations
      in the TWIST gene encoding a basic Helix-Loop-Helix transcription factor. Here we
      report on the identification of a novel mutation affecting a highly conserved
      residue of the basic domain. Unlike nonsense and missense mutations lying within
      helices, this mutation does not affect protein stability or heterodimerisation of
      TWIST with its partner E12. However, it does abolish TWIST binding capacity to a
      target E-box as efficiently as two missense mutations in the loop-helix II
      junction. By contrast, elongation of the loop through a 7 amino acid insertion
      appears not to hamper binding to the DNA target. We conclude that loss of TWIST
      protein function in Saethre-Chotzen patients can occur at three different levels,
      namely protein stability, dimerisation, and DNA binding and that the loop-helix
      II junction is essential for effective protein-DNA interaction.

PMID- 11248248
TI  - Ser(13)-phosphorylated PYY from porcine intestine with a potent biological
      activity.
AB  - We have isolated a posttranslationally modified form of peptide YY (PYY) from
      porcine intestine and shown by MALDI-TOF and electrospray tandem mass
      spectrometry that it is phosphorylated at Ser(13). Phospho-PYY exhibits high
      affinity for binding to neuropeptide Y (NPY) receptors Y1, Y2 and Y5. The IC(50)
      values with the Y1, Y2, and Y5 receptor subtypes were for NPY 2.4, 3.1, and 3.3
      nM, for PYY 2.3, 0.94, and 3.2 nM, and for phospho-PYY 4.6, 2.2, and 5.5 nM,
      respectively. Phospho-PYY potently inhibits forskolin-stimulated cAMP
      accumulation in SK-N-MC cells with an IC(50) value of 0.5 nM compared to 0.15 nM
      for non-phosphorylated PYY. The finding of phosphorylation of PYY is unusual
      among hormonal peptides, and emphasizes the importance of direct protein analysis
      of gene products.

PMID- 11248249
TI  - Decreased antioxidant defense during replicative aging of the yeast Saccharomyces
      cerevisiae studied using the 'baby machine' method.
AB  - Replicatively senescent cells of Saccharomyces cerevisiae were obtained using the
      'baby machine' method by immobilizing cells on CovaLink NH(2) plates and allowing
      them to divide while exchanging medium and removing daughter cells.
      Centrifugation in a Percoll density gradient was employed for further
      purification of replicatively old yeast cells. Comparison of senescent cells
      showing more than 20 bud scars with cells from early stationary culture
      demonstrated a significant reduction of total and reduced glutathione and
      decrease of superoxide dismutase activity during replicative aging of yeast
      cells.

PMID- 11248250
TI  - The fas locus of the phytopathogen Rhodococcus fascians affects mitosis of
      tobacco BY-2 cells.
AB  - The effect of Rhodococcus fascians, the causal agent of leafy gall disease, on
      the mitotic behavior of synchronized tobacco Bright Yellow-2 (BY-2) cells was
      investigated. Incubation of aphidicolin-synchronized BY-2 cells with R. fascians
      cells specifically resulted in a broader mitotic index peak, an effect that was
      linked to an intact and expressed fas virulence locus. The obtained results
      pointed towards an effect of R. fascians on the prophase of mitosis. The
      relevance of these results to the virulence of the bacterium is discussed.

PMID- 11248251
TI  - Involvement of mitochondrial ferredoxin and Cox15p in hydroxylation of heme O.
AB  - Cox15p is essential for the biogenesis of cytochrome oxidase [Glerum et al., J.
      Biol. Chem. 272 (1997) 19088-19094]. We show here that cox15 mutants are blocked
      in heme A but not heme O biosynthesis. In Schizosaccharomyces pombe COX15 is
      fused to YAH1, the yeast gene for mitochondrial ferredoxin (adrenodoxin). A
      fusion of Cox15p and Yah1p in Saccharomyces cerevisiae rescued both cox15 and
      yah1 null mutants. This suggests that Yah1p functions in concert with Cox15p. We
      propose that Cox15p functions together with Yah1p and its putative reductase
      (Arh1p) in the hydroxylation of heme O.

PMID- 11248253
TI  - Isoform-specific inhibition of voltage-sensitive Ca(2+) channels by protein
      kinase C in adrenal chromaffin cells.
AB  - Selective protein kinase C (PKC) activators and inhibitors were used to
      investigate the involvement of specific PKC isoforms in the modulation of voltage
      sensitive Ca(2+) channels (VSCCs) in bovine adrenal chromaffin cells. Exposure to
      the phorbol ester phorbol-12,13-dibutyrate (PDBu) inhibited the Ca(2+) currents
      elicited by depolarizing voltage steps. This inhibition was occluded by the PKC
      specific inhibitor Ro 31-8220 but remained unaffected by Go 6976, a selective
      inhibitor of conventional PKC isoforms. PDBu treatment caused the translocation
      of PKC-alpha and -epsilon isoforms from cytosol to membranes. PKC-iota and -zeta
      showed no signs of translocation. It is concluded that VSCCs are specifically
      inhibited by the activation of PKC-epsilon in chromaffin cells. This may be
      relevant to the action of phospholipase-linked receptors involved in the control
      of Ca(2+) influx, both in catecholaminergic cells and other cell types.

PMID- 11248252
TI  - The Ras GDP/GTP cycle is regulated by oxidizing agents at the level of Ras
      regulators and effectors.
AB  - Reactive oxygen species (ROS) have been found to play important roles in
      regulating cellular functions. Their action in vivo has been related to specific
      effects on signal transduction pathways, such as Ras pathway. In order to
      characterize which elements of Ras pathway are affected by ROS, we have analyzed
      the action of different oxidizing agents on the ability of GTPase activating
      protein GAP and nucleotide exchange factor GEF to enhance the intrinsic
      activities of Ras. The action of these agents on the binding between H-Ras and
      its effector c-Raf-1 was also investigated. No effects were observed on the
      intrinsic activities of H-Ras or Ras2p. On the other hand, reversible inhibitions
      of GEF and GAP actions on Ras were found, whose extent was dependent on the agent
      used. As tested with the scintillation proximity assay, these agents also
      inhibited the binding of c-Raf-1 to H-Ras. Our data reveal new potential targets
      for the action of ROS on Ras pathway and suggest that they can influence the Ras
      activation state indirectly via regulators and effectors.

PMID- 11248254
TI  - Efficient GFP mutations profoundly affect mRNA transcription and translation
      rates.
AB  - Green fluorescent protein (GFP) variants with higher expression efficiencies have
      been generated by mutagenesis. Favorable mutations often improve the folding of
      GFP. However, an effect on protein folding fails to explain the efficiency of
      several other GFP mutations. In this work, we demonstrate that mutations of the
      GFP open reading frame and untranslated regions profoundly affect mRNA
      transcription and translation efficiencies. The removal of the GFP 5'
      untranslated region halves the transcription rate of the GFP gene, but hugely
      improves its translation rate. Mutations of the GFP open reading frame or the
      addition of peptide sequences differentially reduce the GFP mRNA transcription
      rate, translation efficiency and protein stability. These previously unrecognized
      effects are demonstrated to be critical to the efficiency of GFP mutants. These
      findings indicate the feasibility of generating more efficient GFP variants, with
      optimized mRNA transcription and translation in eukaryotic cells.

PMID- 11248255
TI  - Carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) induces initiation
      factor 2 alpha phosphorylation and translation inhibition in PC12 cells.
AB  - We have investigated the effect of the mitochondrial uncoupler carbonyl cyanide p
      trifluoromethoxyphenylhydrazone (FCCP) on protein synthesis rate and initiation
      factor 2 (eIF2) phosphorylation in PC12 cells differentiated with nerve growth
      factor. FCCP treatment induced a very rapid 2-fold increase in intracellular
      Ca(2+) concentration that was accompanied by a strong protein synthesis rate
      inhibition (68%). The translation inhibition correlated with an increased
      phosphorylation of the alpha subunit of eIF2 (eIF2 alpha) (25% vs. 7%, for FCCP
      treated and control cells, respectively) and a 1.7-fold increase in the double
      stranded RNA-dependent protein kinase activity. No changes in the PKR endoplasmic
      reticulum-related kinase or eIF2 alpha phosphatase were found. Translational
      regulation may play a significant role in the process triggered by mitochondrial
      calcium mobilization.

PMID- 11248256
TI  - Crystal structure of the bacterial cell division regulator MinD.
AB  - In bacterial cell division MinD plays a pivotal role, selecting the mid-cell over
      other sites. With MinC, MinD forms a non-specific inhibitor of division, that
      interacts with FtsZ. Specificity is provided by MinD's interaction with MinE at
      the mid-cell. We have solved the crystal structure of MinD-1 from Archaeoglobus
      fulgidus to 2.6 A by multiple anomalous dispersion. MinD is a classic nucleotide
      binding protein, related to nitrogenase iron proteins, which have a fold of a
      seven-stranded parallel beta-sheet, surrounded by alpha-helices. Although MinD,
      unlike the proteins it interacts with and those it is structurally related to, is
      a monomer, not a dimer.

PMID- 11248257
TI  - A new face on apoptosis: death-associated protein 3 and PDCD9 are mitochondrial
      ribosomal proteins.
AB  - Two proteins known to be involved in promoting apoptosis in mammalian cells have
      been identified as components of the mammalian mitochondrial ribosome.
      Proteolytic digestion of whole mitochondrial ribosomal subunits followed by
      analysis of the peptides present using liquid chromatography-tandem mass
      spectrometry revealed that the proapoptotic proteins, death-associated protein 3
      (DAP3) and the programmed cell death protein 9, are both components of the
      mitochondrial ribosome. DAP3 has motifs characteristic of guanine nucleotide
      binding proteins and is probably the protein that accounts for the nucleotide
      binding activity of mammalian mitochondrial ribosomes. The observations reported
      here implicate mitochondrial protein synthesis as a major component in cellular
      apoptotic signaling pathways.

PMID- 11248258
TI  - Different populations of neurons contribute to the detection and discrimination
      of visual motion.
AB  - The signal-to-noise ratio of a direction-selective neuron for 'detecting' visual
      motion is highest when the motion direction is close to the neuron's preferred
      direction. But because these neurons show a bell-shaped tuning for direction,
      they have the highest signal-to-noise ratio for 'discriminating' the direction of
      motion when their preferred direction is off the direction to be discriminated.
      In this paper, we demonstrate with an adaptation paradigm that the visual system
      shows a corresponding task-specific ability to select neurons depending on
      whether it is performing a detection or a discrimination task, relying
      preferentially on different neuronal populations in the two tasks. Detection is
      based on neuronal populations tuned to the test direction, while direction
      discrimination is based on neurons preferring directions 40-60 degrees off the
      test direction.

PMID- 11248260
TI  - Role of motion integration in contour perception.
AB  - Contours are believed to play a key role in the visual analysis of scenes by the
      primate brain. In dynamic scenes, the presence of contours is often signaled by
      discontinuities in motion fields. However, it is unclear whether the motion
      fields over which the visual system extracts discontinuities, correspond to the
      local optic-flow or the pattern motion fields obtained by integrating local
      estimates. A resolution of this issue would provide important clues about the
      organization of visual motion and form analysis processes. In this paper, we
      present experimental evidence which suggests that the perception of motion
      defined contours is strongly dependent on motion integration - an operation that
      is believed to take place relatively late in the visual stream.

PMID- 11248259
TI  - Immunocytochemical and electrophysiological characterization of GABA receptors in
      the frog and turtle retina.
AB  - The expression of GABA receptors (GABARs) was studied in frog and turtle retinae.
      Using immunocytochemical methods, GABA(A)Rs and GABA(C)Rs were preferentially
      localized to the inner plexiform layer (IPL). Label in the IPL was punctate
      indicating a synaptic clustering of GABARs. Distinct, but weaker label was also
      present in the outer plexiform layer. GABA(A)R and GABA(C)R mediated effects were
      studied by recording electroretinograms (ERGs) and by the application of specific
      antagonists. Bicuculline, the GABA(A)R antagonist, produced a significant
      increase of the ERG. Picrotoxin, when co-applied with saturating doses of
      bicuculline, caused a further increase of the ERG due to blocking of GABA(C)Rs.
      The putative GABA(C)R antagonist Imidazole-4-acidic acid (I4AA) failed to
      antagonize GABA(C)R mediated inhibition and, in contrast, appeared rather as an
      agonist of GABARs.

PMID- 11248261
TI  - Edge co-occurrence in natural images predicts contour grouping performance.
AB  - The human brain manages to correctly interpret almost every visual image it
      receives from the environment. Underlying this ability are contour grouping
      mechanisms that appropriately link local edge elements into global contours.
      Although a general view of how the brain achieves effective contour grouping has
      emerged, there have been a number of different specific proposals and few
      successes at quantitatively predicting performance. These previous proposals have
      been developed largely by intuition and computational trial and error. A more
      principled approach is to begin with an examination of the statistical properties
      of contours that exist in natural images, because it is these statistics that
      drove the evolution of the grouping mechanisms. Here we report measurements of
      both absolute and Bayesian edge co-occurrence statistics in natural images, as
      well as human performance for detecting natural-shaped contours in complex
      backgrounds. We find that contour detection performance is quantitatively
      predicted by a local grouping rule derived directly from the co-occurrence
      statistics, in combination with a very simple integration rule (a transitivity
      rule) that links the locally grouped contour elements into longer contours.

PMID- 11248262
TI  - Psychophysics of reading. XX. Linking letter recognition to reading speed in
      central and peripheral vision.
AB  - Our goal is to link spatial and temporal properties of letter recognition to
      reading speed for text viewed centrally or in peripheral vision. We propose that
      the size of the visual span - the number of letters recognizable in a glance -
      imposes a fundamental limit on reading speed, and that shrinkage of the visual
      span in peripheral vision accounts for slower peripheral reading. In Experiment
      1, we estimated the size of the visual span in the lower visual field by
      measuring RSVP (rapid serial visual presentation) reading times as a function of
      word length. The size of the visual span decreased from at least 10 letters in
      central vision to 1.7 letters at 15 degrees eccentricity, in good agreement with
      the corresponding reduction of reading speed measured by Chung and coworkers
      (Chung, S. T. L., Mansfield, J. S., & Legge, G. E. (1998). Psychophysics of
      reading. XVIII. The effect of print size on reading speed in normal peripheral
      vision. Vision Research, 38, 2949-2962). In Exp. 2, we measured letter
      recognition for trigrams (random strings of three letters) as a function of their
      position on horizontal lines passing through fixation (central vision) or
      displaced downward into the lower visual field (5, 10 and 20 degrees ). We also
      varied trigram presentation time. We used these data to construct visual-span
      profiles of letter accuracy versus letter position. These profiles were used as
      input to a parameter-free model whose output was RSVP reading speed. A version of
      this model containing a simple lexical-matching rule accounted for RSVP reading
      speed in central vision. Failure of this version of the model in peripheral
      vision indicated that people rely more on lexical inference to support peripheral
      reading. We conclude that spatiotemporal characteristics of the visual span limit
      RSVP reading speed in central vision, and that shrinkage of the visual span
      results in slower reading in peripheral vision.

PMID- 11248263
TI  - Texture space.
AB  - Many previous studies have examined the ease with which two spatially adjacent
      textures can be segmented. Our goal is to examine the representational system
      that determines the appearance of isolated patches of visual texture. To this
      end, similarity judgments from three subjects were obtained for 20 artificial
      textures comprising filtered noise. Multidimensional scaling (MDS) revealed that
      three perceptual dimensions explain most of the variance in subjects' similarity
      judgments. In addition, the three subjects' similarity judgments and MDS
      solutions were highly correlated. A computational model utilizing the energy
      responses in seven bandpass filters explains an average of 80% of the variability
      in the original similarity scores of individual subjects. In the model, energy
      responses are mapped to the perceptual space through a linear transformation that
      can be decomposed into two components. The first component decorrelates initial
      filter responses and the second component maps the decorrelated filter responses
      to a perceptual space. These latter transformations show remarkable agreement
      between the three subjects.

PMID- 11248264
TI  - Relative roles of 3-D and 2-D coordinate systems in solving the correspondence
      problem in apparent motion.
AB  - There has been a controversy in the apparent motion literature regarding the
      influence of 3-D distances between motion tokens on correspondence matching. The
      current series of experiments indicates that this discrepancy results because the
      effect of three-dimensional distance is too small to be detected unless the
      retinal coordinates of the motion tokens are carefully chosen so as to lead to
      ambiguous correspondence matches on identical trials. It is also shown that, even
      when the retinal coordinates of motion tokens are equated, such that the
      different solutions to the correspondence problem are generated with equal
      probability, the effect of 3-D distances obtained is relatively small when
      compared to the effect of the retinal coordinates of motion tokens.

PMID- 11248265
TI  - Conditions of perceptual selection and suppression during interocular rivalry in
      strabismic and normal cats.
AB  - Presenting the two eyes with incongruent stimuli leads to the phenomenon of
      interocular rivalry. At any given time, one of the stimuli is perceptually
      suppressed in order to avoid double vision. In squinting subjects, rivalry occurs
      permanently also for congruent stimuli because of developmental rearrangement of
      cortical circuitry. In this study, we have investigated the dynamics and stimulus
      dependence of rivalry in six esotropic, four exotropic and three non-strabismic
      cats. As an indicator for perception, we used optokinetic nystagmus that was
      induced by moving gratings. The esotropic cats were tested for their visual
      acuity by means of a jumping stand procedure. The results show that one eye can
      dominate perception even if both eyes have equal visual acuity and are presented
      with stimuli of equal contrast. Strong eye dominance asymmetry was found in all
      but one of the tested cats. Notably, all three of the normal cats showed a clear
      asymmetry in perceptual selection. Measurements with varying contrast and
      velocity of the stimuli revealed that the influence of these parameters on
      perceptual selection was independent of the presence of strabismus. In all cats,
      the time during which a given eye dominated perception increased with the
      contrast and decreases with the velocity of the stimulus presented to this eye.

PMID- 11248266
TI  - Short-term priming, concurrent processing, and saccade curvature during a target
      selection task in the monkey.
AB  - In human subjects, two mechanisms for improving the efficiency of saccades in
      visual search have recently been described: color priming and concurrent
      processing of two saccades. Since the monkey provides an important model for
      understanding the neural underpinnings of target selection in visual search, we
      sought to explore the degree to which the saccadic system of monkeys uses these
      same mechanisms. Therefore, we recorded the eye movements of rhesus monkeys
      performing a simple color-oddity pop-out search task, similar to that used
      previously with human subjects. The monkeys were rewarded for making a saccade to
      the odd-colored target, which was presented with an array of three distractors.
      The target and distractors were randomly chosen to be red or green in each trial.
      Similar to what was previously observed for humans, we found that monkeys show
      the influence of a cumulative, short-term priming mechanism which facilitates
      saccades when the color of the search target happens to repeat from trial to
      trial. Furthermore, we found that like humans, when monkeys make an erroneous
      initial saccade to a distractor, they are capable of executing a second saccade
      to the target after a very brief inter-saccadic interval, suggesting that the two
      saccades have been programmed concurrently (i.e. in parallel). These results
      demonstrate a close similarity between human and monkey performance. We also made
      a new observation: we found that when monkeys make such two-saccade responses,
      the trajectory of the initial saccade tends to curve toward the goal of the
      subsequent saccade. This provides evidence that the two saccade goals are
      simultaneously represented on a common motor map, supporting the idea that the
      movements are processed concurrently. It also indicates that concurrent
      processing is not limited to brain areas involved in higher-level planning;
      rather, such parallel programming apparently occurs at a low enough level in the
      saccadic system that it can affect saccade trajectory.

PMID- 11248267
TI  - Modulation of spatial attention with unidirectional field motion: an implication
      for the shift of the OKN beating field.
AB  - During optokinetic nystagmus (OKN) the mean eye position of gaze (the beating
      field) shifts in the direction of the fast phases. The function of this shift may
      be to re-orient the eyes in the direction of self-motion which optic flow implies
      (in-coming field). This idea leads to the hypothesis that visual attention may be
      directed toward the In-coming field. In Experiment 1, subjects detected a visual
      flash presented against unidirectional field motion. The OKN beating field was
      shifted toward the In-coming field, and manual reaction times were shorter when
      the target appeared in the In-coming field. Experiment 2 revealed that this In
      coming field advantage occurred even when OKN (and thus the mean eye-position
      shift) was suppressed. Subsequent experiments showed that the In-coming field
      advantage is not due to a local motion interaction (Experiment 3), survives
      subject's voluntary allocation of attention (Experiment 4), and develops over
      less than 320 ms after the onset of the motion field (Experiment 5). These
      results suggest that unidirectional field motion tends to automatically shift
      visual attention toward the In-coming field.

PMID- 11248268
TI  - Fixation could simplify, not complicate, the interpretation of retinal flow.
AB  - The visual system must generate a reference frame to relate retinal images in
      spite of head and eye movements. We show how a reference frame for storing the
      visual direction and depth of points can be composed from the angles and changes
      in angles between pairs and triples of points. The representation has no unique
      origin in 3-D space nor a unique set of cardinal directions (basis vectors). We
      show how this relative representation could be built up over a series of
      fixations and for different directions of translation of the observer.
      Maintaining gaze on a point as the observer translates helps in building up this
      representation. In our model, retinal flow is divided into changes in
      eccentricity and changes in meridional angle. The latter, called 'polar angle
      disparities' for binocular viewing (Weinshall, 1990. Computer Vision Graphics and
      Image Processing, 49 222-241), can be used to recover the relief structure of the
      scene in a series of stages up to full Euclidean structure. We show how the
      direction of heading can be recovered by a similar series of stages.

PMID- 11248269
TI  - Filling-in at the natural blind spot contributes to binocular rivalry.
AB  - The human natural blind spot is usually filled in based on the contextual
      information. When two sufficiently different images are presented to the two
      eyes, observers typically perceive an alternation between the two images
      (binocular rivalry). Both the filling-in process and binocular rivalry have been
      the subject of considerable research. This study investigates whether filled
      information in one eye's natural blind spot can contribute to binocular rivalry.
      A radial grating (D=12 degrees ) was presented to one eye, centered on the
      natural blind spot. Observers perceived a complete figure in monocular view; the
      blind spot area was filled-in based on the surrounding information.
      Simultaneously, a circular grating smaller than the blind spot (D=4 degrees ),
      was presented to the fellow eye in the region corresponding to the other eye's
      blind spot. The amount of rivalry as indexed by how often the smaller circular
      grating remained visible was measured. The results suggest that the filled
      information in the area of the blind spot does contribute to the rivalry process.

PMID- 11248270
TI  - Glutamate regulates the viability of retinal cells in culture.
AB  - In this study, we show that glutamate regulates the viability of cultured retinal
      cells upon transient glucose deprivation. At low concentrations (10-100 microM)
      glutamate decreased MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide] reduction to about 50% of control and decreased intracellular ATP levels
      (about 4-fold) after transient glucose removal. Under these conditions, the
      decrease in MTT reduction was associated with the activation of NMDA (N-methyl-D
      aspartate) receptors. Upon exposure to high (10 mM) glutamate and transient
      glucose deprivation, the intracellular levels of glutamate increased. High
      glutamate significantly counteracted the decrease in MTT reduction and ATP
      production observed in the presence of low glutamate concentrations. AOAA
      (aminooxyacetic acid), a non-specific inhibitor of mitochondrial transaminases,
      enhanced the intracellular glutamate levels, but did not largely affect glutamate
      mediated changes in MTT reduction or ATP production. Furthermore, the
      intracellular levels of pyruvate were not significantly altered, suggesting that
      changes in ATP production were not due to an increase in glycolysis. Thus, the
      recovery from glucose deprivation seems to be facilitated in retinal neuronal
      cells that had been exposed to high glutamate, in comparison with low glutamate,
      suggesting a role for high glutamate and glucose in maintaining retinal cell
      function following conditions of glucose scarcity.

PMID- 11248271
TI  - Dual oriented mechanisms in contour interaction.
AB  - Foveal visual acuity is impaired by the presence of contours that surround the
      target (contour interaction (CI)). In order to determine the roles of various
      surrounding contours, visual acuities for a square C were measured in the
      presence of four and two flanking bars. Bars of different orientations relative
      to the gap of the C produced different CI patterns. The CI produced by a pair of
      bars was alleviated by adding another pair of bars of an orthogonal orientation.
      These results indicate that CI is mediated by not one, but at least two
      orientation selective mechanisms that actively inhibit each other.

PMID- 11248272
TI  - The consequences of opponent rectification: the effect of surround size and
      luminance on color appearance.
AB  - Smith and Pokorny (Vision Res. 36 (1996) 3087.) described conditions under which
      chromatic contrast induction can reveal a hiatus, a region of chromaticity space
      which appears neither reddish nor greenish when presented in a chromatic
      equiluminant surround. The current study investigated the effect of varying the
      size and the luminance of the inducing surround. The color appearance of test
      stimuli in chromatic surrounds was assessed by asymmetric color matching to a
      comparison display. Equiluminant (12 cd/m(2)), 1 degrees square stimuli were
      generated on a CRT display and presented haploscopically. Ten test fields varied
      in their L-cone excitation along a constant S-cone line. The chromatic surrounds
      were of either high (red) or low (green) L-cone excitation on a constant S-cone
      line. In Experiment 1, surrounds were 1.1 degrees, 1.5 degrees, 2.0 degrees, or
      3.0 degrees square (surround widths of 3', 15', 30', 1 degrees ). In Experiment
      2, the test and comparison surrounds were at higher (16.7 cd/m(2)) or lower (8.3
      cd/m(2)) retinal illuminance than the test field. Contrast induction reached an
      asymptote for surround widths of 30' or larger. The amount of induction decreased
      for the surround widths of 15' and 3'. The hiatus was present for the larger
      surrounds and decreased as surround size decreased. The use of a higher or lower
      surround luminance did not affect the magnitude of induction or the size of the
      hiatus.

PMID- 11248273
TI  - A binocular site for contrast-modulated masking.
AB  - Contrast-modulated (CM) gratings, composed of two luminance-modulated sinusoids
      of similar spatial frequency, mask the detection of test sinusoids at the
      difference frequency. However, the mechanism underlying masking by CM gratings
      remains poorly understood. In this paper, we aimed to determine whether the
      masking of 1 cycle deg(-1) LM test gratings by a 1 cycle deg(-1) beat (formed
      from a pair of carriers at 8 and 9 cycles deg(-1)) occurs in monocular channels
      or after the site of binocular combination, or both. Threshold elevations for the
      detection of a 1 cycle deg(-1) test grating were obtained for a number of
      stimulus conditions, including: (1) dichoptic CM (both 8 and 9 cycles deg(-1)
      mask components presented to one eye, with the 1 cycle deg(-1) test grating to
      the other); (2) dichoptic variant (8 and 9 cycles deg(-1) mask gratings presented
      to separate eyes, with the 1 cycle deg(-1) test grating presented to one eye);
      (3) binocular CM (all mask and test gratings presented to both eyes). As a
      control, masking magnitude was also measured for LM mask gratings of similar
      frequency (1 cycle deg(-1)) and effective contrast (3%) to that of the beat. For
      both LM and CM masks, the dichoptic condition yielded threshold elevations that
      were similar or greater than the binocular condition. When 8 and 9 cycles deg(-1)
      mask components were presented to separate eyes (the dichoptic variant
      condition), no beat pattern was visible and no elevations in detection threshold
      occurred. The results demonstrate that, like LM masking, detection of a target in
      the presence of a CM mask does not involve purely monocular mechanisms. Further,
      that the site of CM masking must occur beyond the stage at which monocular
      matching for stereopsis takes place. This is consistent with other studies which
      suggest that dichoptic masking is contingent on stereo matching, and thus occurs
      relatively late in the hierarchy of binocular visual processing.

PMID- 11248274
TI  - Adaptation to disparity but not to perceived depth.
AB  - The purpose of the present study was to investigate whether adaptation can occur
      to disparity per se. The adapting stimuli were large random-dot patterns of which
      the two half-images were transformed such that the depth effects induced by the
      vertical transformations were nulled by horizontal transformations. Thus, the
      adapting stimuli were perceptually the same, whereas the disparity fields
      differed from each other. The adapting stimuli were presented for five minutes.
      During that period, the percept of a fronto-parallel surface did not change.
      After the adapting period, subjects perceived a thin untransformed strip as
      either slanted or curved depending on the adapting transformation. The thin
      strips provided negligible information about the vertical disparity field. In a
      forced-choice task we measured the amount of horizontal transformation that was
      required to null the acquired adaptation. We found that the amounts of horizontal
      transformation required to perceive the test strip fronto-parallel were
      significantly different from zero. We conclude that the visual system can adapt
      to disparity signals in the absence of a perceptual drive.

PMID- 11248275
TI  - Chromatic detection and discrimination analyzed by a Bayesian classifier.
AB  - Detection and threshold-level discrimination of Gabor patches were studied under
      the conditions of noise masking, in an attempt to isolate 'higher-order' or
      nonclassical color mechanisms. Detection contours in the equiluminant plane of
      cone contrast space were measured by varying test chromaticity in the presence of
      chromatic masking noise. Three equiluminant noise directions were used, in
      separate experiments. In the discrimination experiment, observers had to
      discriminate between pairs of stimuli that were fixed at their masked threshold
      contrasts. A Bayesian color classifier model was used to analyze the
      discrimination data, with no free parameters. There was no evidence of
      nonclassical color mechanisms in either the detection or discrimination data.

PMID- 11248276
TI  - Isolated short-wavelength sensitive cones can mediate a reflex accommodation
      response.
AB  - Both long- and middle-wavelength sensitive cones mediate the reflex accommodation
      signal but the contribution from the short-wavelength sensitive cones is unknown.
      A short-wavelength sensitive cone contribution could extend the range of the
      signed defocus signal from chromatic aberration. The aim was to determine whether
      isolated short-wavelength sensitive cones mediate reflex accommodation
      independently of long- and middle-wavelength sensitive cones. Accommodation was
      monitored continuously (eight subjects) to a sine-wave grating (3 cpd; 0.53
      contrast) moving with a sum of sines motion in a Badal optometer. Two
      illumination conditions were used: a 'blue' condition that isolated short
      wavelength sensitive cones, and a 'white' control condition that stimulated all
      three cone types. Of the eight subjects, two responded equally in the 'white' and
      'blue' condition, four gave reduced responses in the 'blue' condition and two
      failed to respond in both conditions. The mean response in the 'blue' condition
      was reduced by 50% compared to the 'white' condition. Further analysis indicated
      that four of the eight subjects gave responses that were considerably greater
      than noise (S.D.>1.82) when short-wavelength sensitive cones were isolated. Some
      subjects can accommodate using only S-cones.

PMID- 11248277
TI  - Fixation disparity and accommodation for stimuli closer and more distant than
      oculomotor tonic positions.
AB  - Both the vergence and the accommodative system have individual tonic positions
      (also referred to as dark vergence and dark focus, respectively) where the static
      response may be expected to be most accurate. This was confirmed by measuring
      fixation disparity with nonius lines and accommodation with an autorefractometer
      for foveal stimuli at viewing distances of 460, 100, 60, 40, and 30 cm. Multiple
      regression analysis was used at each viewing distance to predict fixation
      disparity from dark vergence, dark focus, accommodative gain and accommodative
      convergence: these accommodative measures had little effect on the inter
      individual variability of near fixation disparity nor on the linear slope of
      fixation disparity as a function viewing distance.

PMID- 11248278
TI  - Perception of relation of stimuli locations successively flashed before saccade.
AB  - Based on localization error for a single perisaccadic flash, eye position signal
      is supposed to change more slowly than physical eye position. Nevertheless, a
      flicker is not perceived as moving in accordance with localization error for a
      single flash. We carried out two experiments to investigate this problem.
      Experiment 1 examined how a single flash or a flicker presented before saccade
      was perceived. The results showed that the flicker was not perceived as moving,
      although mislocalization for the single flash increases gradually before saccade.
      Experiment 2 was a vernier test of two stimuli successively flashed before the
      saccade. The results showed that the point of subjective equality shifted in
      accordance with the mislocalization for a single perisaccadic flash when the
      interstimulus interval (ISI) was about 2 s; however, it did not shift when the
      ISI was 78 ms. Comparison between these results and previous studies suggests
      that the relation of the locations of successive flashes before saccade is
      perceived exocentrically when the ISI and stimulus onset asynchrony between
      flashes was short.

PMID- 11248279
TI  - Eye movement control in reading: word predictability has little influence on
      initial landing positions in words.
AB  - We examined the initial landing position of the eyes in target words that were
      either predictable or unpredictable from the preceding sentence context. Although
      readers skipped over predictable words more than unpredictable words and spent
      less time on predictable words when they did fixate on them, there was no
      difference in the launch site of the saccade to the target word. Moreover, there
      was only a very small difference in the initial landing position on the target
      word as a function of predictability when the target words were fixated which is
      most parsimoniously explained by positing that a few programmed skips of the
      target word fell short of their intended target. These results suggest that low
      level processing is primarily responsible for landing position effects in
      reading.

PMID- 11248280
TI  - Occlusions contribute to scaling in natural images.
AB  - Spatial power spectra from natural images fall approximately as the square of
      spatial frequency, a property also called scale invariance (scaling). Various
      theories for visual receptive fields consider scale invariance key. Two
      hypotheses have been advanced in the literature for why natural images obey scale
      invariance. The first is that these images have luminance edges, whose spectra
      fall as frequency squared. The second is that scale invariance follows from
      natural images being essentially a collage of independent, constant-intensity
      regions, whose sizes follow a power-law distribution. Recently, an argument by
      example was made against the first hypothesis. Here we refute that argument and
      show that the first hypothesis is consistent with the scaling under a wide
      variety of distributions of sizes. There are two reasons for this: first, for
      every frequency, the log-log slope of the rotationally averaged power spectrum of
      an image is the weighted mean of the log-log slopes from the independent regions
      of the image formed by objects occluding one another. Second, the log-log slopes
      of the spectrum envelope for a constant-intensity region are 0 and -3 for
      frequencies corresponding to periods much larger and much smaller than the
      region's size, respectively. Therefore, it is not surprising that natural images
      have log-log slopes between -1.5 and -3, with a mean near -2.

PMID- 11248281
TI  - IOC, vector sum, and squaring: three different motion effects or one?
AB  - Bowns (Vision Research, 36(22) (1996), 3685) argued that there are distinct
      features in two-component moving patterns (plaids) that if tracked move in the
      same direction as (1) the intersection of constraints direction (IOC) Adelson and
      Movshon (Nature, 300 (1992), 523); and (2) the vector sum direction (VS) Yo and
      Wilson (Vision Research, 32(1) (1992), 135). The IOC and VS are hypotheses of how
      the motion of single components is combined to give pattern motion. This paper
      shows that there are also features that provide an explanation for a reversed
      motion described by Derrington, Badcock, and Holroyd (Vision Research, 32(4),
      (1992), 699), and investigates why reversals only occur under specific
      conditions. Section 3 replicates the original study by Derrington et al. (1992)
      and confirms that the reversals are limited to low temporal frequencies. Section
      4 varies the spatial displacement of features that also predict reversals and
      shows that the temporal frequency at which reversals occur varies and is linearly
      dependent on the displacement of these specified features. Derrington et al.
      (1992) showed that reversals only occur when components have oblique angles, and
      suggested an explanation in terms of speed differences. Section 5 was not
      consistent with this hypothesis. An alternative explanation for why reversals
      only occur at oblique angles, and at low spatial frequencies is provided in terms
      of feature properties. Results supporting the IOC, vector sum, and squaring have
      previously been interpreted in terms of three disparate mechanisms. This may not
      be necessary.

PMID- 11248282
TI  - A dysfunctional factor X (factor X San Giovanni Rotondo) present at homozygous
      and double heterozygous level: identification of a novel microdeletion (delC556)
      and missense mutation (Lys(408)-->Asn) in the factor X gene. A study of an
      Italian family.
AB  - Low levels of factor X (F.X) were detected in a 4-year-old boy who experienced
      acute lymphoblastic leukemia and bleeding manifestations. Laboratory data
      suggested the presence of a dysfunctional F.X molecule. Two novel F.X gene
      mutations were identified in the proband that was double heterozygous for both: a
      microdeletion (delC556) in exon VI resulting in a frameshift leading to a
      termination codon at position 226. This deletion was found in six family members
      with reduced F.X antigen and activity levels. A second mutation characterised by
      a G(1344)-->C transversion in exon VIII was detected in the proband resulting in
      a Lys(408)-->Asn substitution. This latter mutation was present in several
      asymptomatic family members from the paternal and the maternal side. The
      proband's sister was homozygous for the Lys(408)-->Asn substitution and exhibited
      low F.X activity with a normal antigen level. The naturally occurring F.X
      Lys(408)-->Asn (F.X(K408N)) variant was isolated from plasma of either homozygous
      or double heterozygous individuals. NH(2)-terminal sequencing of the heavy chain
      of F.X(K408N) failed to show any sequence abnormality in patients who were also
      carriers of the delC556, suggesting that this latter lesion accounted for the
      lack of F.X synthesis. Purified F.X Lys(408)-->Asn had an identical behaviour to
      normal F.X as judged by SDS-PAGE and immunoblotting. Clotting assay using
      purified F.X(K408N) and F.X-deficient plasma resulted in a laboratory phenotype
      similar to that observed in a homozygous subject for F.X Lys(408)-->Asn
      substitution. This is the first characterisation of a naturally occurring F.X
      variant with a mutation at the COOH-terminal end of the molecule.

PMID- 11248283
TI  - Evidence for the existence of the PAF acetylhydrolase mutation (Val279Phe) in non
      Japanese populations: a preliminary study in Turkey, Azerbaijan, and Kyrgyzstan.
AB  - Deficiency of plasma platelet-activating factor (PAF) acetylhydrolase resulting
      from a missense mutation (Val279Phe) in exon 9 of the gene has been described
      exclusively in the Japanese population with a very high frequency. This study
      describes the distribution of the mutation in Turkey and two other Turkic
      nations, Kyrgyzstan in central Asia and Azerbaijan bordering the Caspian Sea.
      Among 358 unrelated healthy subjects studied from Turkish population, only 3 had
      the mutation in heterozygous state (0.84%). Family studies also revealed the
      presence of homozygous individuals in close relatives of one of these subjects.
      Among 143 healthy subjects studied from Kyrgyzstan, 12 were heterozygous for the
      mutation (8.4%). No mutation was detected among 100 healthy individuals studied
      from Azerbaijan. However, it was suggested that the number of subjects was not
      enough to draw any conclusion about the prevalence of the mutation in the
      populations studied. Contrary to the previous notions, identification of the
      mutation in Turkey and Kyrgyzstan shows the existence of the mutation in non
      Japanese populations as well.

PMID- 11248285
TI  - Anticoagulant pharmacodynamics of tinzaparin following 175 iu/kg subcutaneous
      administration to healthy volunteers.
AB  - Tinzaparin, a sodium salt of a low-molecular-weight heparin (LMWH) produced via
      heparinase digestion, is used for the treatment of deep vein thrombosis (DVT) and
      pulmonary embolism in conjunction with warfarin for the prevention of DVT in
      patients undergoing hip or knee replacement surgery, and as an anticoagulant in
      hemodialysis circuits. Its average molecular weight ranges between 5500 and 7500
      daltons (Da); the percentage of chains with molecular weight lower than 2000 Da
      is not more than 10% in the marketed tinzaparin formulation. While this fraction
      is generally considered pharmacologically inactive, this has never been evaluated
      in vivo. The importance of the < 2000 Da fraction on the anticoagulant
      pharmacodynamics of tinzaparin assessed by anti-Xa and anti-IIa activity was
      studied in a two-way crossover trial. In this trial, 30 healthy volunteers
      received a single 175 IU/kg subcutaneous administration of tinzaparin containing
      approximately 3.5% of the < 2000 Da fraction and a tinzaparin-like LMWH
      containing 18.3% of the < 2000 Da fraction. The anti-Xa/anti-IIa ratios of the
      drug substances were comparable at 1.5 and 1.7 for tinzaparin and the tinzaparin
      like LMWH, respectively. Both formulations were safe and well tolerated. Mean
      maximum plasma anti-Xa activity (A(max)) was approximately 0.818 IU/ml at 4 h
      following tinzaparin injection. Mean maximum plasma anti-IIa activity was 0.308
      IU/ml at 5 h postdose. Intersubject variation was lower (< 18% for both anti-Xa
      and anti-IIa metrics) than in previous fixed-dose administration studies. There
      was no correlation between anti-Xa or anti-IIa AUC or A(max) and bodyweight in
      the present study supporting the weight-adjusted dosing regimen. Individual anti
      Xa and anti-IIa profiles following the single 175 IU/kg subcutaneous
      administration of the tinzaparin-like LMWH were similar to that obtained with
      tinzaparin. Based on average equivalence criteria, the two LMWH preparations were
      determined to be bioequivalent using either anti-Xa or anti-IIa activity as
      biomarkers. The calculated intrasubject variabilities were low (< 14% for anti-Xa
      activity and < 18% for anti-IIa activity) yielding little evidence for a
      significant Subject x Formulation interaction. In summary, anti-Xa and anti-IIa
      activity following a single subcutaneous administration of tinzaparin 175 IU/kg
      to healthy volunteers yielded activity consistent with targeted therapeutic
      levels derived from previous trials in adult DVT patients. Weight-based dosing
      for the treatment of DVT appears rational based on the reduction in anti-Xa and
      anti-IIa variability consistent with the recommendation derived from earlier
      fixed-dose pharmacokinetic studies. Furthermore, differences in the percentage of
      molecules in the < 2000 Da molecular weight fraction of tinzaparin do not
      translate into differences in anti-Xa and anti-IIa activity in vivo.

PMID- 11248284
TI  - Effect of thrombophylaxis on uterine and fetal circulation in pregnant women with
      a history of pregnancy complications.
AB  - PURPOSE: The aim of this study was to investigate the effect of
      thromboprophylactic therapy on fetal and maternal Doppler flow parameters in
      pregnant women with severe complications in previous pregnancies and evidence of
      acquired or congenital thrombophilia in the current pregnancy. METHODS: Sixty
      five patients with a history of recurrent abortions, intrauterine fetal death,
      intrauterine growth restriction (IUGR), and severe early-onset preeclampsia were
      tested for the presence of acquired or congenital thrombophilia. Those with
      positive findings were prescribed low-dose aspirin plus low-molecular-weight
      heparin (LMWH) (enoxaparin); the remainder received low-dose aspirin only. A
      Doppler flow study was performed before and after treatment and in the third
      trimester of pregnancy. RESULTS: Of the 65 pregnancies, four ended in spontaneous
      abortion and were excluded from the analysis. Of the 61 women with completed
      pregnancies, 37 (61%) had evidence of acquired or congenital thrombophilia: 22
      (36%) protein S deficiency; 1 (2%) protein C deficiency; 2 (3%) activated protein
      C resistance (APC-R); 2 (3%) IgG for antiphospholipid antibodies; 1 (2%)
      circulating anticoagulant; and 9 (15%) a combined defect. This group showed a
      significant decrease in mean uterine artery pulsatility index (PI) before and
      after treatment (1.32+/-0.36 vs. 1.04+/-0.23, P=.006), whereas the remaining 24
      patients treated with low-dose aspirin only had nonsignificant changes. Pearson's
      correlation test yielded no correlations of the pregnancy outcome parameters with
      Doppler flow values in the umbilical or uterine arteries. CONCLUSIONS:
      Thromboprophylactic therapy transiently improves maternal circulation parameters
      in patients with thrombophilia at risk of fetal loss and other severe
      complications of pregnancy, but not in correlation with their pregnancy outcome.
      Therefore, Doppler examination of maternofetal circulation in the second
      trimester is not predictive of pregnancy outcome.

PMID- 11248287
TI  - D-dimer testing as the initial test for suspected pulmonary embolism.
      Appropriateness of prescription and physician compliance to guidelines.
AB  - OBJECTIVES: Recent studies have shown that strategies for pulmonary embolism
      diagnosis which have included D-dimer testing have been most cost effective. The
      objective of this study is to evaluate the impact of a new strategy for pulmonary
      embolism diagnosis based on D-dimer results. METHODS: A prospective survey was
      conducted in the emergency ward and three medical departments of a university
      teaching hospital. Guidelines for diagnosis of PE were established and
      implemented through an educational intervention and a specific order form. D
      dimer (ELISA) was required for all patients suspected of having PE. A result
      above 500 ng/ml was to be followed by an a pulmonary imaging procedure.
      Appropriateness of prescription of D-dimer and non-compliance with guidelines
      (absence of diagnostic imaging procedure following D-dimer results above 500
      ng/ml) were evaluated. RESULTS: One-hundred sixty patients were studied. D-dimer
      test was performed in 154 patients (96.3%) suspected of PE during a two-month
      period. Test results were above 500 ng/ml in 111 cases. PE was confirmed in 20
      cases. Twenty percent (31/154) of the D-dimer prescriptions were inappropriate.
      Among those with D-dimer results above 500 ng/ml, 45% (50/111) of the patients
      experienced no imaging procedure. CONCLUSIONS: Despite implementation of clinical
      guidelines for its use, D-dimer was excessively prescribed. A large proportion of
      results was not taken in consideration by prescribers. Often new technologies
      have good experimental results, but behave differently when used routinely in
      ordinary care settings. It is important that field studies be developed to
      evaluate the effectiveness of new technologies.

PMID- 11248286
TI  - A common C-->T polymorphism at nt 46 in the promoter region of coagulation factor
      XII is associated with decreased factor XII activity.
AB  - Coagulation factor XII (FXII) deficiency is rarely found to be associated with
      bleeding, but single reports demonstrated thromboembolic events in FXII-deficient
      patients. Currently, the biological role of FXII is still discussed
      controversially. It is well known that plasma levels of FXII show great
      interindividual variability. Recently, it has been demonstrated that a frequently
      occurring C-->T polymorphism in the FXII promoter region at nucleotide (nt) 46 is
      associated with lower plasma FXII activity levels in Orientals. In our study, we
      evaluated the frequency of this polymorphism in a randomly selected sample of
      newborns and investigated whether this C-->T polymorphism also contributes to the
      frequently observed moderate FXII deficiency in Europeans. We developed a new
      mutagenically separated polymerase chain reaction assay (MS PCR), which allows
      mutation detection without the use of restriction enzymes. Among 100 healthy
      newborns, we found 64% homozygous carriers of the wildtype FXII 46C allele, 29%
      were heterozygous for FXII C46T, and 7% homozygous for FXII 46T. Evaluation of
      plasma FXII activity and genotype in 80 randomly selected and unrelated
      individuals revealed a highly statistically significant (P<.001) association of
      the FXII 46T allele with reduced FXII plasma activity. Individuals carrying the
      homozygous FXII 46C genotype had a mean of 1.17 U/ml (+/-0.31 U/ml), individuals
      heterozygous for FXII C46T showed a mean of 0.70 U/ml (+/-0.31 U/ml), and
      subjects homozygous for FXII 46T had only 0.44 U/ml (+/-0.10 U/ml) plasma FXII
      activity.

PMID- 11248288
TI  - Northern elephant seal platelets: analysis of shape change and response to
      platelet agonists.
AB  - Blood platelets have a vital role in the maintenance of normal mammalian
      hemostasis. Rapid pressure changes and temperatures lower than 20 degrees C cause
      activation of human and terrestrial mammal platelets. Elephant seals are
      routinely subjected to pressures as high as 150 atm, yet do not suffer from the
      thrombotic effects of platelet activation associated with rapid decompression. We
      examined the ultrastructure of Northern elephant seal (Mirounga angustirostris)
      platelets and their functional and morphological response to various platelet
      agonists. Unstimulated elephant seal platelets are discoid cells, with a
      microtubule coil, randomly dispersed alpha and dense granules, and glycogen
      granules. There are well-defined areas of membranous invaginations that indicate
      the presence of an open canalicular system (OCS). Aggregometry was used to
      determine the response of elephant seal platelets to various platelet agonists.
      Dose-dependent curves were generated for thrombin, collagen, and adenosine
      diphosphate (ADP). Platelet response to thrombin was dose-dependent and was
      maximal at 2.5 U/ml. Platelets collected in sodium citrate had blunted responses
      to both ADP and collagen. ADP stimulation caused only reversible, primary
      activation (shape change) at > or = 5 microM, while platelets did not aggregate
      in response to any concentration of collagen. Platelets collected in sodium
      heparin did respond fully to both to ADP and collagen. There was small,
      reversible shape change in response to ristocetin, but no response to
      epinephrine. Decreased sensitivity of elephant seal platelets to agonists may be
      a protective mechanism developed in response to rapid pressure changes and cold
      temperatures associated with adaptation to an extreme environment.

PMID- 11248289
TI  - The CC chemokines MDC and TARC induce platelet activation via CCR4.
AB  - While chemokines have received considerable attention for their role in leukocyte
      chemotaxis, their effects on platelets have not been well described. We found
      that two CC chemokine receptor 4 (CCR4) ligands, macrophage-derived chemokine
      (MDC) and thymus and activation-regulated chemokine (TARC) induce concentration
      dependent platelet aggregation and calcium flux. Flow cytometric analysis
      revealed the expression of CCR4 on platelets and a monoclonal antibody (mAb) to
      CCR4 inhibited MDC- and TARC-induced platelet aggregation, confirming that this
      effect is mediated through their common receptor CCR4. MDC fully desensitized
      TARC-induced calcium mobilization in platelets, while TARC was unable to
      completely desensitize a subsequent MDC response, which is similar to
      observations made in Th2 CD4(+) lymphocytes and CCR4-transfected cells. Aspirin
      (ASA) treatment of platelets allowed reversible primary aggregation but inhibited
      irreversible complete aggregation, suggesting that MDC- and TARC-induced full
      platelet aggregation is dependent on cyclooxygenase metabolites of arachidonic
      acid. MDC and TARC were unable to induce platelet aggregation and platelet
      secretion in washed human platelets, even though they induced a calcium flux,
      suggesting that plasma components are required for MDC- and TARC-induced platelet
      aggregation. Since Th2-type cytokines induce the release of MDC and TARC from
      cells and the expression of these chemokines is increased in Th2-type
      inflammation, we hypothesize that MDC and TARC may play a role in platelet
      activation seen in Th2 diseases, such as asthma and atopic dermatitis.

PMID- 11248290
TI  - Differential effects of enzymatic treatments on the storage and secretion of von
      Willebrand factor by human endothelial cells.
AB  - Enzymatic treatment used for passaging of endothelial cells may induce release of
      von Willebrand factor (vWF). Decreased ability to replenish intracellular stores
      results in decreased secretion of vWF in later passages of cells. Since both
      trypsin and pancreatin complex have been used for passaging endothelial cells, we
      analyzed the effects of successive passaging with these two enzyme preparations
      on the storage and secretion of vWF by human umbilical vein endothelial cells
      (HUVECs). Measurements were performed after the second to fifth passages.
      Cytoplasmic vWF was analyzed by indirect immunofluorescence and secreted vWF was
      measured in the supernatant of cultured HUVECs by ELISA. In trypsin-passaged
      cells, secreted vWF decreased progressively from passages 2 to 5. Respective
      concentrations were 355.0 +/- 30.4, 201.0 +/- 84.5, 150.0 +/- 1.4 and 120.5 +/-
      38.9 ng vWF/10(5) cells. Comparatively, pancreatin-passaged cells secreted even
      less vWF protein (P = .001) at passages 4 and 5 (108.5 +/- 12.0 and 100.0 +/- 4.2
      ng/10(5) cells, respectively) and had less vWF-positive cytoplasmic granules per
      cell. Thus, in experiments involving measurements of endothelial vWF, the use of
      low passage cells is recommendable and passaging with a pure trypsin preparation
      appears to be more appropriate.

PMID- 11248291
TI  - Analysis of the activated partial thromboplastin time test using mathematical
      modeling.
AB  - Activated partial thromboplastin time (APTT) is a laboratory test for the
      diagnosis of blood coagulation disorders. The test consists of two stages: The
      first one is the preincubation of a plasma sample with negatively charged
      materials (kaolin, ellagic acid etc.) to activate factors XII and XI; the second
      stage begins after the addition of calcium ions that triggers a chain of calcium
      dependent enzymatic reactions resulting in fibrinogen clotting. Mathematical
      modeling was used for the analysis of the APTT test. The process of coagulation
      was described by a set of coupled differential equations that were solved by the
      numerical method. It was found that as little as 2.3 x 10(-9) microM of factor
      XIIa (1/10000 of its plasma concentration) is enough to cause the complete
      activation of factor XII and prekallikrein (PK) during the first 20 s of the
      preincubation phase. By the end of this phase, kallikrein (K) is completely
      inhibited, residual activity of factor XIIa is 54%, and factor XI is activated by
      26%. Once a clot is formed, factor II is activated by 4%, factor X by 5%, factor
      IX by 90%, and factor XI by 39%. Calculated clotting time using protein
      concentrations found in the blood of healthy people was 40.5 s. The most
      pronounced prolongation of APTT is caused by a decrease in factor X
      concentration.

PMID- 11248292
TI  - A dysfunctional factor X (factor X Kurayoshi) with a substitution of Arg 139 for
      Ser at the carboxyl-terminus of the light chain.

PMID- 11248294
TI  - Microvascular decompression in the treatment of hypertension: review and update.
AB  - BACKGROUND: Neurogenic hypertension in association with vascular compression of
      the left rostral ventrolateral medulla has been documented. A recent group of
      these clinical reports has raised great interest in decompression of this area of
      the brainstem as a definitive therapy for essential hypertension. METHODS: To
      further clarify the mechanism by which decompression of the left rostral
      ventrolateral medulla relieves neurogenic hypertension, we describe in detail the
      basic science, animal models, human studies, and most recent clinical trials
      regarding surgical decompression of this area. CONCLUSION: Multi-disciplinary
      evidence supports the hypothesis that a sub-population of hypertensive patients
      achieve significant relief of their hypertension after microvascular
      decompression. A multi-institutional, prospective, randomized study is necessary
      to determine the efficacy of microvascular decompression for neurogenic
      hypertension.

PMID- 11248297
TI  - Myocardial stunning secondary to aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND: Although subarachnoid hemorrhage (SAH) is often associated with
      electrocardiographic abnormalities, profound effects on cardiac performance are
      rare. CASE DESCRIPTION: A 57-year-old woman who developed loss of consciousness,
      respiratory distress, severe hypotension, and left ventricular hypokinesis with
      minimal coronary artery disease is described. Despite normal appearance of the
      coronary arteries on angiography, left ventricle function was so severely
      depressed that she required intra-aortic balloon pump support for 24 hours.
      Mental status changes prompted a head computed tomographic (CT) scan, which
      showed severe SAH and an intraventricular hemorrhage (IVH). Cerebral angiography
      demonstrated a basilar apex aneurysm. An echocardiogram done on hospital day 6
      was normal. A left frontal ventriculostomy catheter was placed. This was later
      changed to a lumbar subarachnoid (SA) drain. The patient underwent an orbito
      zygomatic craniotomy and aneurysm clipping. Although several serious medical
      problems occurred during her hospitalization, at follow-up, her sole neurological
      impairment was a minimal and resolving oculomotor paresis. CONCLUSION: This
      patient's respiratory failure and severe hypotension were initially thought to be
      due to a chemical pneumonitis or a cardiomyopathy. However, her symptoms
      ultimately proved to be secondary to a ruptured basilar apex aneurysm. The
      complex relationship of SAH to myocardial stunning, as illustrated by this
      patient, is discussed.

PMID- 11248299
TI  - Posterior approach for soft cervical disc herniation: a neglected technique?
AB  - BACKGROUND: The ideal approach to the treatment of soft cervical disc herniation
      remains controversial. Recent reports emphasize several variations of anterior
      cervical approaches, including the introduction of instrumentation techniques.
      New issues have been raised and modern neurosurgeons seem to be less familiar
      with the posterior approach. The objective of this study was to analyze the
      results obtained by surgical treatment via a posterior approach of soft cervical
      disc herniation. METHOD: Fifty-one patients who underwent laminectomy/flavectomy
      and disc removal for the treatment of soft cervical disc herniation in the period
      of 1990 to 1999 were analyzed retrospectively. Relief of pain and motor and
      sensory improvement were the criteria used to measure the success of the
      procedure. RESULTS: Most of the patients presented with acute radiculopathy.
      Radicular involvement was as follows: 25 cases-C7 root, 19 cases-C6 root, 4 cases
      C5 root, and 3 cases-C8 root. Total relief of pain was obtained in 49 of 51
      patients (96%). Motor improvement was obtained in 35 of 46 patients (76%) and
      sensory improvement in 22 of 35 patients (62.8%) in the short term. The mean time
      of hospitalization was 3 days. There was no mortality and no morbidity.
      CONCLUSION: The advantage of this method, in selected cases, over the classical
      anterior approach, is that there is no need for grafting, thus avoiding the
      additional pain and possible complications at the donor and receptor sites, while
      obtaining similar results.

PMID- 11248301
TI  - Urinary retention following routine neurosurgical spine procedures.
AB  - BACKGROUND: The rate and duration of urinary retention after routine cervical and
      lumbar spine procedures were studied. METHODS: Preoperative, intraoperative, and
      postoperative factors related to urinary retention (age, sex, duration of
      operation, medications, Foley use, hospital stay, and cost) were analyzed in a
      retrospective review of 503 patients' charts. RESULTS: Urinary retention occurred
      38% of the time following cervical and lumbar spine procedures. Advanced age and
      preoperative beta blockers contributed to a higher incidence of urinary
      retention. Preoperative anti-inflammatory medications and narcotic analgesics
      reduced the frequency of urinary retention. The duration of urinary retention was
      prolonged in older patients and patients who underwent intraoperative Foley
      catheterization. Urinary retention contributed to longer hospitalization and
      increased hospital costs. CONCLUSIONS: Transient urinary retention is a common
      complication of routine neurosurgical spine procedures that prolongs hospital
      stays and increases the costs of hospitalization.

PMID- 11248307
TI  - Vertebral artery pseudoaneurysm complicating posterior C1-2 transarticular screw
      fixation: case report.
AB  - BACKGROUND: Vertebral artery injury during posterior C1-2 transarticular screw
      fixation occurs in approximately 3% of patients and may remain asymptomatic or
      result in arteriovenous fistulae, occlusion, narrowing, or dissection of the
      vertebral artery, and lead to transient ischemic attacks, stroke, or death. CASE
      DESCRIPTION: This is the first report of a pseudoaneurysm resulting from damage
      to the vertebral artery during the procedure. This 31-year-old male underwent
      posterior C1-2 transarticular screw fixation for unstable os odontoideum. Injury
      to the left vertebral artery occurred while the hole for the left screw was being
      drilled. Temporary control of bleeding with local pressure was followed by
      immediate postoperative angiography that revealed a left vertebral artery
      pseudoaneurysm. Although the patient remained asymptomatic, therapeutic
      anticoagulation was instituted 6 hours postoperatively. Increasing size of the
      pseudoaneurysm was noted on routine follow-up angiography 4 weeks later.
      Endovascular occlusion of the pseudoaneurysm and left vertebral artery, with
      preservation of vertebrobasilar flow through the right vertebral artery, was
      accomplished without neurological consequence. CONCLUSIONS: Vertebral artery
      pseudoaneurysm complicating posterior C1-2 transarticular screw fixation may be
      effectively treated with endovascular approaches.

PMID- 11248310
TI  - Traumatic occipitoatlantal dislocation.
AB  - BACKGROUND: Traumatic occipitoatlantal dislocation (OAD) is a severe ligamentous
      injury resulting in instantaneous death or severe neurological deficit. However,
      survivors of OAD, both short and long term, have been increasingly reported; this
      may be because of improved prehospital care, more rapid transportation, a high
      index of suspicion, and new radiological techniques. METHODS: The medical records
      and film of three patients who had traumatic OAD were retrospectively reviewed.
      Diagnosis was made by lateral cervical spine radiography, computed tomography
      (CT), or magnetic resonance imaging (MRI). Treatment consisted of early
      respiratory support and subsequent posterior surgical fusion. RESULTS: The three
      survivors of traumatic OAD represent 3.1% of all cervical spine injuries in our
      service. Two were children and the other was a 64-year-old man, all of whom
      suffered from severe neurological deficits. Lateral cervical spine radiographs
      led to the diagnosis of OAD. Two were longitudinal, and one was anterior. Two
      patients died within 2 weeks after injury. The remaining patient, who had
      anterior OAD, survived longer, which allowed posterior fusion with a U-shape
      Steinman pin and wiring to be performed. However, she died 5 months after injury
      because of septicemia. CONCLUSION: Early recognition and treatment may improve
      the outcome of this injury. Treatment consists of early respiratory support and
      subsequent surgical fusion.

PMID- 11248312
TI  - Secondary tumor formation after stereotactic biopsy for intracerebral metastatic
      disease.
AB  - BACKGROUND: There are only a few published cases of iatrogenic tumor seeding and
      distant neoplastic growth along the path of the cannula after stereotactic
      biopsy. CASE DESCRIPTION: We report the case of a female patient with a solitary
      lung cancer metastasis in the left parietal brain lobe. The tumor was
      stereotactically biopsied and treated by radiosurgery. One month after the
      initial biopsy, a smaller de novo tumor mass located along the track of the
      stereotactic cannula was detected by contrast-enhanced MRI. The spatial location
      of this neoplastic nodule and the short time before development of a macroscopic
      lesion seemed to confirm iatrogenic tumor cell spread due to the stereotactic
      procedure. CONCLUSION: Our findings and the reviewed literature suggest that this
      complication is rare. Nevertheless, neurosurgeons should be aware of the
      potential risk and, if necessary, should be able to modify the technical
      procedure and the adjuvant treatment.

PMID- 11248313
TI  - Galactorrhea as the sole presenting symptom of a posterior third ventricular
      epidermoid cyst.
AB  - BACKGROUND: Brain tumors that are remote from the sellar and parasellar region
      rarely produce galactorrhea. CASE DESCRIPTION: Galactorrhea was the sole
      presenting symptom in a patient with a posterior third ventricular epidermoid
      cyst. On investigation, her serum prolactin level was mildly elevated. After
      radical excision of the tumour, the spontaneous galactorrhea stopped and the
      serum prolactin level decreased. CONCLUSION: Because of the clinical and
      biochemical response seen after surgery, we speculate that the galactorrhea was
      caused by the presence of the tumor. We postulate that the pressure exerted by
      the tumor on the diencephalic structures was probably the cause of galactorrhea
      in our patient.

PMID- 11248315
TI  - B-mode ultrasonographic investigations of morphological changes in
      endarterectomized carotid artery.
AB  - BACKGROUND: The aim of this study was to assess morphological changes in the
      endarterectomized carotid region using B-mode ultrasonography (USG). METHODS: USG
      examinations were performed on 54 Japanese patients who underwent carotid
      endarterectomy (CEA). The endarterectomized regions were periodically
      investigated and the intima-media thickness (IMT) was measured. RESULTS:
      Postoperative USGs revealed an evident step formation (type I: 20.4%), a gentle
      slope (type II: 42.6%), or complete smoothness (type III: 37.0%) at the junction
      of the endarterectomized carotid region and the common carotid artery (CCA). The
      IMT of the CCA progressively increased from type I to type III. Patients were
      followed up for an average of 2.7 years. The new intima-media complex (IMC) was
      confirmed in all cases after 9 months; it was visualized as an isoechoic layer
      (7%) or a mixture of iso- and hypoechoic layers (93%). Changes in the IMT during
      the follow-up period were classified into three groups: no change (group I:
      23.1%), decrease (group II: 15.4%), and increase (group III: 61.5%). CONCLUSIONS:
      USG is useful to clarify the complicated healing processes of the
      endarterectomized carotid artery.

PMID- 11248318
TI  - Spontaneous middle cerebral artery occlusion leading to moyamoya phenomenon and
      aneurysm formation on collateral arteries.
AB  - BACKGROUND: Spontaneous middle cerebral artery occlusion associated with moyamoya
      phenomenon is distinct from moyamoya disease. The hemodynamic stress on the
      collateral channel occasionally leads to aneurysm formation, which may manifest
      as hemorrhage. The etiology of this disease has not been fully understood. CASE
      DESCRIPTION: A 63-year-old woman presented with left putaminal hemorrhage. The
      cerebral angiogram revealed a significant stenosis in the proximal segment of the
      left middle cerebral artery. Collateral arteries originating from the horizontal
      segment of the ipsilateral anterior cerebral artery and the ambient segment of
      the ipsilateral posterior cerebral artery supplied the middle cerebral artery
      distal to the stenosis. Both of the collateral channels had associated aneurysms
      that were surgically obliterated. The aneurysm on the collateral artery from the
      posterior cerebral artery was responsible for the putaminal hemorrhage.
      CONCLUSIONS: Spontaneous middle cerebral artery occlusion may lead to focal
      moyamoya phenomenon and aneurysmal intracerebral, intraventricular, or
      subarachnoid hemorrhage. The presence of a co-existing anomalous collateral
      artery in the present case suggests a congenital etiology of the focal middle
      cerebral artery occlusion.

PMID- 11248320
TI  - Calvarial hemangiomas: report of two cases and review of the literature.
AB  - BACKGROUND: Primary hemangiomas of the bone are uncommon tumors, accounting for
      less than 1.0% of all bone neoplasms. These tumors are mostly found in vertebral
      bodies. Hemangiomas are rarely seen in the calvarium, where their frequency is
      0.2% of all bone neoplasms. Because of their infrequent appearance in the skull,
      vague symptoms, and absence of prototypical radiological findings, these tumors
      can be missed in many cases or may be misinterpreted as more ominous lesions like
      multiple myeloma or osteosarcoma. CASE DESCRIPTION: We report two cases of
      calvarial hemangiomas: one with a single mass on the right sphenoid wing, and
      another with two similar lesions on the right occipital and left parietal bones.
      The diagnoses could be established only by histopathologic analysis. CONCLUSION:
      Histopathologic confirmation of the tumor is the definitive method for diagnosis
      of intraosseous hemangiomas. Radiological findings are not always characteristic
      for calvarial hemangiomas. Due to possible complications and the possibility of
      effective treatment, this lesion should always be considered in the differential
      diagnosis of skull lesions.

PMID- 11248323
TI  - Neurosurgery 2000.

PMID- 11248324
TI  - Clinical relevance of Flt1 and Tie1 angiogenesis receptors expression in B-cell
      chronic lymphocytic leukemia (CLL).
AB  - Angiogenesis, a complex process tightly controlled by several molecules including
      vascular endothelial growth factor (VEGF) and basic fibroblast growth factor
      (bFGF) along with their receptors, plays a major role in the growth and
      metastasis of solid tumors. The expression and production of VEGF and bFGF have
      been documented in numerous solid tumors and hematopoietic neoplasms. Having
      recently shown increased expression of cellular VEGF in the leukemic cells of
      patients with chronic lymphocytic leukemia (CLL) we decided to investigate the
      expression of angiogenic receptors Flt1 and Tie1. Levels of Tie1 and Flt1
      proteins were measured in leukemic cells from 231 patients with B-cell CLL using
      Western blot analysis and solid-phase radioimmunoassay (RIA). A strong
      correlation was found between Flt1 and Tie1 levels and white blood cell count
      (WBC) and absolute lymphocyte counts. Levels of Flt1 but not Tie1 correlated with
      levels of cellular VEGF. Interestingly, Tie1 correlated well with Rai stage
      (P=0.04). Flt1 and Tie1 did not correlate with survival, although when we
      evaluated the patients with early disease (Rai stage 0-II), higher levels of Tie1
      but not of Flt1 correlated with worse survival. These data suggest that Tie1
      plays a role in the early stages of B-cell CLL and as the disease progresses, the
      tumor cells become independent from the effects of Tie1. Further studies are now
      needed to dissect the mechanisms responsible for this phenomenon.

PMID- 11248325
TI  - Prognostic value of lactate dehydrogenase activity in myelodysplastic syndromes.
AB  - Several prognostic factors for patients with myelodysplastic syndromes (MDS) have
      been defined in the past. One of these factors appears to be the serum lactate
      dehydrogenase (LDH) activity. However, the precise predictive value of an
      elevated LDH level with regard to AML transformation remains uncertain. In this
      study, the prognostic value of the LDH activity was examined in a cohort of 180
      patients with de novo MDS (median age 71 years [27-93]; f/m-ratio 1:1.2; RA:
      n=53; RARS: n=37; RAEB: n=50; RAEBT: n=19; CMML: n=21). Significant differences
      in LDH activities were found among FAB groups (P<0.05), and especially among IPSS
      groups (HIGH: 411+/-574; INT-2: 221+/-90; INT-1: 254+/-145; LOW: 192+/-47 U/l;
      P<0.05). An LDH level of >/=300 U/l was found to be associated with a
      significantly shorter median survival (10.3 months) when compared to <300 U/l
      (33.7 months; P<0.01). Moreover, an LDH activity of >/=300 U/l indicated a
      reduced AML-free survival in our MDS patients (P<0.01). As assessed by Cox
      regression, the inclusion of LDH as additional variable into the IPSS system
      resulted in an improved prediction concerning survival, but not with regard to
      AML evolution. Together, our data show that a serum LDH activity of >/=300 U/l in
      MDS is associated with a significantly shorter survival and higher risk to
      transform to AML. The LDH activity should be considered as an important
      prognostic factor in MDS.

PMID- 11248326
TI  - In vitro characterization of the hematopoietic system in pediatric patients with
      acute lymphoblastic leukemia.
AB  - Acute lymphoblastic leukemia (ALL) has been recognized as a hematologic neoplasia
      that originates at the level of a primitive lymphoid stem/progenitor cell. To
      date, however, the biology of the hematopoietic system in this disorder is still
      not fully understood. In the present study, we have determined the progenitor
      cell content (including myeloid, erythroid and multipotent progenitors) in 14
      children with ALL and followed the proliferation kinetics of these cells in
      Dexter-type long-term marrow cultures. We have also characterized some aspects
      related to the composition and function of the hematopoietic microenvironment
      developed in vitro. All patients included in this study showed extremely reduced
      levels of progenitor cells (median of 6.2% of the levels found in normal marrow).
      Proliferation of these cells in long-term cultures was markedly deficient, since
      they showed very low numbers - compared to normal cultures - and reached
      undetectable levels after only a few weeks. Regarding the microenvironment
      developed in vitro, whereas normal marrow samples contained a median of 8
      fibroblastic progenitors/10(5) marrow cells and the stromal cell layers developed
      in culture contained a median of 341000 adherent cells per well, ALL marrow
      samples showed no fibroblastic progenitors and the numbers of adherent cells were
      21% of those in normal cultures. Interestingly, the levels of TNFalpha and IL-6
      in ALL culture supernatants were significantly increased, compared to normal
      cultures. Bone marrow samples from all 14 children were also analyzed once they
      reached a complete clinical and hematological remission. Myeloid, erythroid and
      multipotent progenitor cell levels were significantly increased, compared to
      patients at diagnosis, and proliferation of myeloid progenitors in long-term
      cultures was also improved. In contrast, proliferation of erythroid progenitors
      showed no difference to that in cultures from patients at diagnosis. The numbers
      of fibroblastic progenitors and adherent cells were significantly increased,
      compared to patients at diagnosis, and TNFalpha and IL-6 levels returned to
      normal. In summary, in the present study, we have demonstrated significant in
      vitro alterations of the hematopoietic system, both in terms of its composition
      and function, in pediatric patients with ALL. Importantly, most of these
      alterations are corrected, at least partially, after chemotherapy.

PMID- 11248327
TI  - Combination chemotherapy of intermediate-dose cytarabine, idarubicin, plus
      etoposide and subsequent mobilized donor leukocyte infusion for relapsed acute
      leukemia after allogeneic bone marrow transplantation.
AB  - The efficacy and side effects of intermediate-dose cytarabine, idarubicin plus
      etoposide and subsequent donor leukocyte infusion (DLI) were investigated in
      patients with acute leukemia who relapsed after allogeneic bone marrow
      transplantation (BMT). Patients were given cytarabine continuous i.v. (1 g/m2 per
      day x 5), idarubicin i.v. (12 mg/m2 per day x 3), and etoposide i.v. infusion
      (150 mg/m2 per day x 3). Two days later, G-CSF mobilized donor leukocytes were
      infused for 2 days. No graft-versus-host disease (GVHD) prophylaxis was given.
      Between August 1997 and February 2000, 13 patients enrolled (eight acute myeloid
      leukemia (AML) and five acute lymphoblastic leukemia (ALL)). All patients
      finished chemotherapy and DLI. Eleven patients (85%) achieved complete remission
      (CR) at median 27 days after DLI. After median follow up of 10.9 months (2.5
      33.3), five of 11 patients who achieved CR relapsed. Overall, six of 13 patients
      were surviving (6/8 AML and 0/5 ALL, P=0.059). Marrow recovery after chemotherapy
      and DLI was rapid (12 days for absolute neutrophil count (ANC) >500/microl). Side
      effects included fever with neutropenia (100%), pneumonia (46%), grade II-IV
      mucositis (69%), grade III-IV acute GVHD (45%), and extensive chronic GVHD (64%).
      One patient died from chronic GVHD. Chemotherapy containing intermediate-dose
      cytarabine and DLI produced a high CR rate in acute leukemia in relapse after
      allogeneic BMT. A fraction of patients are surviving long term. Side effects were
      substantial but manageable.

PMID- 11248328
TI  - Complete karyotype characterization of the K562 cell line by combined application
      of G-banding, multiplex-fluorescence in situ hybridization, fluorescence in situ
      hybridization, and comparative genomic hybridization.
AB  - This study combines conventional cytogenetics, fluorescence in situ hybridization
      (FISH), multiplex-FISH and comparative genomic hybridization (CGH). In applying
      this multimodal approach on the human leukemia cell line K562, the chromosome
      composition was refined in detail and compared with data from the literature. A
      hypotriploid karyotype with a modal chromosome number of 67, and 21 unique marker
      chromosomes were identified. The classification of six markers was identical to
      published data and the composition of five further markers from the literature
      could be fully clarified for the first time. The composition of another five
      markers, which have been interpreted in divergent ways in different studies, were
      elucidated without doubt. Finally, five new markers of our study seem to have no
      equivalents in former studies, very likely due to limitations of conventional
      cytogenetics. The combinatory application of complementary techniques as shown in
      this study will be very useful to provide the basis of a refined genotype
      analysis on the chromosomal level.

PMID- 11248330
TI  - Mutation analysis of the DNA-damage checkpoint gene CHK2 in myelodysplastic
      syndromes and acute myeloid leukemias.
AB  - Checkpoint genes code for a family of proteins which sense DNA damage in
      eukaryotic cells. They play an important role in the control of the cell cycle.
      The human CHK2 is a homolog of the yeast G(2) checkpoint kinases known as CDS1
      and RAD53. The CHK2 may be a tumor suppressor gene because it was found to be
      mutated in some individuals with the Li-Fraumeni syndrome. These cases had a
      normal, non-mutated p53 gene. We performed a mutational analysis of the CHK2 gene
      using polymerase chain reaction-single strand conformation polymorphism (PCR
      SSCP) in 41 bone marrow samples from individuals with myelodysplastic syndrome
      (MDS) and 41 samples of acute myeloid leukemias (AML). We found a novel G to C
      transversion resulting in a change from Ala to Gly at codon 507 of CHK2 in one
      MDS sample, but normal cells from this individual did not have the abnormality.
      In addition, we demonstrated a previously described polymorphism at codon 84 (A
      to G at nucleotide 252) of exon 1 of CHK2 in three of 41 MDS and three of 41 AML
      patients. The presence of a CHK2 mutation in MDS highlights the importance of
      alterations of cell cycle checkpoint genes in this disease.

PMID- 11248329
TI  - A mechanism of apoptosis induced by all-trans retinoic acid on adult T-cell
      leukemia cells: a possible involvement of the Tax/NF-kappaB signaling pathway.
AB  - In this study, five single clones were randomly established by limiting dilution
      method from each of the HTLV-I positive T cell lines - HUT 102 and ATL-2, and
      examined for the all-trans retinoic acid (ATRA) sensitivity, respectively. For
      each clone, we found a significant correlation between the reduction in 3[H]
      thymidine incorporation and the reduction in CD25 expression (r=0.701, P<0.05)
      following treatment with 10(-5) M ATRA for 48 h. Agarose gel electrophoresis
      revealed DNA fragmentation of the cell lines treated with ATRA, indicative of
      apoptosis. These results suggested that the tax gene in the HTLV-I genome might
      be a key molecule involved in cell proliferation and CD25 expression. Thereafter,
      we transfected the tax gene in the expression vector (pCMV-Tax-neo) into the HTLV
      I(-) T cell line Jurkat and examined the effects of ATRA on cell growth. The
      results showed that ATRA sensitivity was acquired by the Jurkat cells transfected
      with the tax gene expression vector, but not in those transfected with the
      control vector. We also observed NF-kappaB transcriptional activity on Jurkat
      cells transfected with the tax gene by CAT assay in the presence or absence of
      ATRA. NF-kappaB transcriptional activity was decreased significantly on Jurkat
      cells transfected with the tax gene after ATRA treatment. Taken together, these
      results indicate that ATRA may affect or block the Tax/NF-kappaB signaling
      pathway in ATL cells.

PMID- 11248331
TI  - Induction of granulocytic differentiation in acute promyelocytic leukemia cells
      (HL-60) by water-soluble chitosan oligomer.
AB  - Water-soluble chitosan oligomer (WSCO) has been reported to have anticancer
      activity, immuno-enhancing effect and antimicrobial activity. However, other
      biological activities are unknown. Herein, we have shown that WSCO is able to
      inhibit proliferation of human leukemia HL-60 cells and induce these cells to
      differentiate. Treatment with WSCO for 4 days resulted in a concentration
      dependent reduction in HL-60 cell growth as measured by cell counting and MTT
      assay. This effect was accompanied by a marked increase in the proportion of
      G(0)/G(1) cells as measured by flow cytometry. WSCO also induced differentiation
      of the cells as measured by phorbol ester-dependent reduction of NBT,
      morphological changes as examined by Wright-Giemsa staining and expression of
      CD11b but not of CD14 as analysed by flow cytometry, indicating differentiation
      of HL-60 cells toward granulocyte-like cells. A combination of low dose of WSCO
      with all-trans retinoic acid, a differentiating agent toward granulocyte-like
      cells, exhibited a synergistic effect on the differentiation. In addition,
      treatment of HL-60 cells with WSCO for 6 or 8 days resulted in the induction of
      apoptosis as assayed qualitatively by agarose gel electrophoresis and
      quantitatively by Annexin V technique using flow cytometry. Collectively, there
      is a potential for WSCO in the treatment of myeloid leukemia.

PMID- 11248332
TI  - A 46, XY, dup (1) (q21q32), add(11) (q23) karyotype in a case of Fanconi anemia.

PMID- 11248333
TI  - New reciprocal translocation t(6;10) (q27;q11) associated with idiopathic
      myelofibrosis and eosinophilia.
AB  - Idiopathic myelofibrosis (IM), is a chronic myeloproliferative disorder (MPD)
      characterised by marrow fibrosis, extramedullary haematopoiesis and a leuco
      erythroblastic picture of the peripheral blood. Cytogenetic data of IM is scarce:
      no specific karyotypic anomalies have been yet described. Trisomy 1q, del(13q),
      del(20q) and trisomy 8, appear in two-thirds of the cases with chromosome
      aberrations. We report on a 41-year-old patient diagnosed with IM associated with
      eosinophilia, bearing a novel translocation t(6;10)(q27;q11) as the sole
      chromosome anomaly. The patient, progressed to AML-M5a within 18 months from
      diagnosis. Recently new specific chromosomal translocations have been described
      in chronic MPD. These findings have allowed the classification of new syndromes
      with defined molecular abnormalities. The case we describe, because of the
      peculiar clinical features and the association with a previously unreported
      chromosomal translocation, might be a noteworthy addition.

PMID- 11248334
TI  - Donor lymphocyte infusion followed by interferon-alpha plus low dose cyclosporine
      A for modulation of donor CD3 cells activity with monitoring of minimal residual
      disease and cellular chimerism in a patient with first hematologic relapse of
      chronic myelogenous leukemia after allogeneic bone marrow transplantation.
AB  - A 15-year-old girl with Ph-positive chronic myelogenous leukemia in first chronic
      phase received bone marrow from her human leukocyte antigen matched brother.
      Twenty three months after bone marrow transplantation hematological relapse
      occured which was treated with two infusions of donor lymphocytes (DLI)
      (0.5x10(8) CD3/kg b.w./infusion). To enforce the graft-versus-leukemia effect
      (GvL), the first DLI was followed by administration of interferon-alpha (INF
      alpha) 6x10(6) U/day for 30 days, whereas, after the second infusion INF-alpha
      was given at the same dose until hematological remission was achieved (80 doses).
      Minimal residual disease (MRD) was detected by conventional cytogenetics (Ph
      chromosome), fluorescence in situ hybridization (FISH) cytogenetics (BCR/ABL
      translocation) and reverse transcriptase-polymerase chain reaction (RT-PCR)
      Ecotropic virus integration site-1 (EVI-1 gene expression), whereas cellular
      chimerism was monitored by assessment of microsatellite markers PCR and Y
      chromosomal DNA content FISH. When hematological remission was achieved the
      pancytopenia was observed and the cytogenetic and molecular investigations
      revealed only partial remission and mixed chimerism, however, with predominance
      of donor origin hematopoiesis. To diminish the myelosupressive effect of donor
      CD3 cells without switching-off the GvL effect, a low dose of cyclosporine A was
      given. Further observation revealed significant improvement of hematopoiesis with
      parallel gradual decline of MRD and increase of donor hematopoiesis up to
      complete chimerism. Graft-versus-host disease was not observed at any stage of
      the treatment.

PMID- 11248335
TI  - Reproducible high efficiency gene transfer into Y79 retinoblastoma cells using
      adenofection.
AB  - Several photoreceptor-specific genes are actively transcribed in Y79
      retinoblastoma (Rb) cells, making this cell line potentially useful for the study
      of photoreceptor metabolism. The utility of these cells is limited because
      commonly used methods of gene transfer into Y79 cells are inefficient and lack
      reproducibility. In contrast, we found that adenovirus transduction yields high
      efficiency gene transfer, however, generation of recombinant adenovirus is
      lengthy and time consuming. Here, we show that adenofection, a method of coupling
      adenovirus to plasmid DNA for improved gene transfer, is efficient for gene
      delivery into Y79 cells. Recombinant adenovirus expressing bacterial lacZ was
      noncovalently complexed to GFP or luciferase reporter plasmids with
      polyethylenimine. Efficiency of plasmid gene delivery was determined by
      monitoring GFP fluorescence. For comparison, calcium phosphate-mediated or
      cationic lipid transfection was performed in Y79 and HEK293 cells using standard
      protocols. The adenofection protocol yielded significantly higher efficiencies in
      Y79 cells than that obtained in these cells with calcium phosphate or cationic
      lipids. This method will facilitate any experiment requiring reproducible high
      level gene transfer. Here, we show that adenofection can be used to analyze
      activity of the rod photoreceptor PDE6A gene promoter.

PMID- 11248336
TI  - Radioactive 33-P probes in hybridization to glass cDNA microarrays using neural
      tissues.
AB  - cDNA microarrays are becoming widespread tools in the study of complex gene
      expression patterns with applications using cells lines, animal model systems,
      and human disease. Glass cDNA microarrays using fluorescent labeled cDNA probes
      require a large amount of input RNA usually not available in many neuroscience
      applications. Here we demonstrate a technique for the use of 33-P labeled cDNA
      probes in hybridizations to the same glass cDNA arrays used for fluorescent
      applications. This approach allows the use of low quantities of RNA, common
      phosphoimaging scanners, data acquisition software, and standard DNA and RNA
      labeling protocols, while being consistent and interchangeable with glass-based
      cDNA array technology.

PMID- 11248337
TI  - Partial, graded losses of dopamine terminals in the rat caudate-putamen: an
      animal model for the study of compensatory adaptation in preclinical
      parkinsonism.
AB  - Procedures to lesion dopamine (DA) neurons innervating the rat caudate-putamen
      (CP) in a partial, graded fashion are described in this study. The goal is to
      provide a lesion model that supports intra-animal comparisons of voltammetric
      recordings used to investigate compensatory adaptation of DA neurotransmission.
      Lesions exploited the topography of mesostriatal DA neurons, microinjections of
      the neurotoxin 6-hydroxydopamine (6-OHDA) into the medial and lateral edges of
      the ventral mesencephalon containing DA cell bodies and microdissection of the CP
      into six regions. Analysis of tissue DA content in these regions by HPLC-EC
      demonstrated that 6-OHDA injected into the lateral substantia nigra results in a
      significantly greater loss of DA in lateral versus medial regions of the CP. The
      direction of the graded loss of DA was reversed (i.e. a medial to lateral lesion
      gradient) by the injection of 6-OHDA into the ventral tegmental area near the
      medial SN. Extracellular concentrations of electrically evoked DA could be
      measured across the mediolateral axis of the CP in a single animal using the
      technique of in vivo voltammetry. More importantly, graded decreases in the
      amplitude of evoked DA levels generally followed the direction of the tissue DA
      gradient in lesioned animals. These results suggest that the graded loss of DA
      terminals in the CP, coupled to a spatially and temporally resolved technique for
      monitoring extracellular DA, is a viable tool for investigating compensatory
      adaptation in the mesostriatal DA system.

PMID- 11248338
TI  - Synthesizing spatially complex sound in virtual space: an accurate offline
      algorithm.
AB  - The study of spatial processing in the auditory system usually requires complex
      experimental setups, using arrays of speakers or speakers mounted on moving arms.
      These devices, while allowing precision in the presentation of the spatial
      attributes of sound, are complex, expensive and limited. Alternative approaches
      rely on virtual space sound delivery. In this paper, we describe a virtual space
      algorithm that enables accurate reconstruction of eardrum waveforms for arbitrary
      sound sources moving along arbitrary trajectories in space. A physical validation
      of the synthesis algorithm is performed by comparing waveforms recorded during
      real motion with waveforms synthesized by the algorithm. As a demonstration of
      possible applications of the algorithm, virtual motion stimuli are used to
      reproduce psychophysical results in humans and for studying responses of barn
      owls to auditory motion stimuli.

PMID- 11248339
TI  - The pasta matrix reaching task: a simple test for measuring skilled reaching
      distance, direction, and dexterity in rats.
AB  - Skilled forelimb use has been used in many studies to examine motor system
      status, learning, and recovery from nervous system damage in rats. The dependent
      measures in many current skilled reaching models rely on endpoint measures,
      number of successful reaches, or qualitative measures, the movements used in
      performing a reach. The present study describes a new reaching task, which allows
      measurement of distance and direction of skilled forelimb movement while also
      permitting end point and qualitative measurements. Animals reached from a clear
      Plexiglas box through an aperture to retrieve pieces of straight, uncooked pasta
      from an array of 260 vertically oriented pieces of pasta arranged in rows
      distally and laterally away from the aperture (a matrix). By extending the range
      of a reach, more pasta is obtained. Limb movements, pieces of pasta removed, and
      the pattern of pasta removal are dependent measures. The usefulness of the test
      is demonstrated using control, dorsal column lesion, and unilateral dopamine
      depleted animals. The task uses a desired food, tests learning and skill, the
      range of limb movement, and the ability to reach for different distances and
      directions. The task can also be modified to investigate other features of limb
      use including skill adjustments, laterality, and force.

PMID- 11248340
TI  - Tools for physiology labs: an inexpensive high-performance amplifier and
      electrode for extracellular recording.
AB  - The cost of electronic equipment can be a critical barrier to including
      neurophysiology exercises in biology teaching programs. We describe the
      construction of a simple and inexpensive AC preamplifier with performance
      comparable to that of commercial products. The amplifier consists of two
      integrated circuits in five stages: differential input, fixed gain, variable gain
      (100 or 1000), low-pass filter (5 or 20 kHz), and 50 or 60 Hz notch filter. We
      compared our amplifier with two commercial units, the A-M Systems Model 1700 and
      the Grass P15. The quality of extracellular recording from a typical student
      preparation (spontaneously active crayfish motor nerve) was the same for all
      three amplifiers, although our amplifier has slightly higher internal noise than
      the P15 and slightly lower common-mode rejection than the 1700 and P15. In
      addition, we describe a simple suction electrode for extracellular nerve
      recording. It is easily constructed from readily available materials and uses a
      disposable plastic pipette tip, instead of the traditional glass tip, to contact
      the nerve. This tip is easily replaced if broken or clogged, and can be adapted
      to different recording conditions by selecting a different tip size or stretching
      the plastic. Development of this equipment is part of an ongoing project to
      promote neuroscience education by expanding the neurophysiology options available
      to laboratory instructors.

PMID- 11248341
TI  - A reconsideration of sound calibration in the mouse.
AB  - Although it is traditional to perform sound calibrations in anesthetized animals
      by placing a probe-tube microphone near the tympanic membrane, these measurements
      are inaccurate at high stimulus frequencies where hearing must be quantified in
      the mouse. Hence, our motivation to develop another approach using the mouse ear
      canal as a coupler. Results of real-ear-canal calibrations indicate that an
      average calibration can be used to estimate sound pressure levels in the three
      mouse strains tested. Similar estimates were also obtained using a tubing
      coupler, whose volume was comparable to that of the ear canal, thereby offering a
      simpler alternative. In addition, real-head calibrations were also performed to
      provide a procedure that can be used in situations where the ear is not
      dissected, as in measurements of the auditory brainstem response. Calibrations
      for open, rather than closed, sound-delivery systems were also evaluated using a
      modified method of substitution.

PMID- 11248342
TI  - Multiple microelectrode-recording system for human intracortical applications.
AB  - The human brain is dominated by the neocortex, a large folded surface, whose
      cellular and synaptic elements are arranged in layers. Since cortical structure
      is relatively constant across its surface, local information processing can be
      inferred from multiple laminar recordings of its electrical activity along a line
      perpendicular to its surface. Such recordings need to be spaced at least as close
      together as the cortical layers, and need to be wideband in order to sample both
      low frequency synaptic currents as well as high-frequency action potentials.
      Finally, any device used in the human brain must comply with strict safety
      standards. The current paper presents details of a system meeting these criteria,
      together with sample results obtained from epileptic subjects undergoing acute or
      chronic intracranial monitoring for definition of the epileptogenic region.

PMID- 11248343
TI  - Macrostructural EEG characterization based on nonparametric change point
      segmentation: application to sleep analysis.
AB  - In the present investigation a new methodology for macrostructural EEG
      characterization based on automatic segmentation has been applied to sleep
      analysis. A nonparametric statistical approach for EEG segmentation was chosen,
      because it minimizes the need for a priori information about a signal. The method
      provides the detection of change-points i.e. boundaries between quasi-stationary
      EEG segments based on the EEG characteristics within four fundamental frequency
      bands (delta, theta, alpha and beta). Polysomnographic data of 18 healthy
      subjects were analyzed. Our findings show that nonparametric change-point
      segmentation in combination with cluster analysis enables us to obtain a clear
      picture of the hierarchical macrostructural organization of sleep, which is
      impossible to deduce from the unsegmented EEG data. Analysis of correlations
      between classically defined sleep stages and piecewise stationary power step
      functions reveals that three basic patterns can be distinguished: SWS (stage
      III/stage IV), stage II and stage I/REM. In accordance with correlation analyses,
      cluster detection shows that the cyclic sleep patterns during the course of the
      night become clearly observable by implementation of only three classes. Since
      the described methodology is based on a minimum of a priori assumptions, it may
      be useful for the development of a new sleep classification standard, which goes
      beyond the established Rechtschaffen and Kales scheme.

PMID- 11248344
TI  - Computer experiments to determine whether over- or under-counting necessarily
      affects the determination of difference in cell number between experimental
      groups.
AB  - Computer cell counting experiments were performed in order to examine the
      consequences of over- or under-counting. The three-dimensional reaggregate
      culture laboratory environment for cell counting was used as a model for computer
      simulation. The laboratory environment for aggregate and cell sizes, numbers and
      spatial placement in gelatin blocks was mimicked in the computer setup. However,
      in the computer, cell counting was set to be either ideally unbiased, or
      deliberately biased in regard to over- or under-counting so as to compare
      eventual results when using the various cell counting methods. It was found that
      there was no effect of the cell counting methods used in determining whether
      there was a significant difference in cell number between two experimental
      groups. In addition, it was found that under the conditions of these simulations,
      the optical dissector method behaved similarly, on the average, as the ideal
      method of counting cell centers and in both of those cases, the average ratio
      between actual cell number in a flask and estimated number was close to 1.00.

PMID- 11248345
TI  - Optimal filtering of whole nerve signals.
AB  - Electroneurographic recordings suffer from low signal to noise (S/N) ratios. The
      S/N ratio can be improved by different signal processing methods including
      optimal filtering. A method to design two types of optimal filters (Wiener and
      Matched filters) was developed for use with neurographic signals, and the
      calculated filters were applied to nerve cuff recordings from the cat S1 spinal
      root that were recorded during the activation of cutaneous, bladder, and rectal
      mechanoreceptors. The S1 spinal root recordings were also filtered using various
      band-pass (BP) filters with different cut-off frequencies, since the frequency
      responses of the Wiener and Matched filters had a band-pass character. The mean
      increase in the S/N ratio across all recordings was 54, 89, and 85% for the
      selected best Wiener, Matched, and band-pass filters, respectively. There were no
      statistically significant differences between the performance of the selected
      filters when all three methods were compared. However, Matched filters yielded a
      greater increase in S/N ratio than Wiener filters when only two filtering
      techniques were compared. All three filtering methods have in most cases also
      improved the selectivity of the recordings for different sensory modalities. This
      might be important when recording nerve activity from a mixed nerve innervating
      multiple end-organs to increase the modality selectivity for the nerve fibers of
      interest. The mean Modality Selectivity Indices (MSI) over different receptor
      types and for the same selected filters as above were 1.12, 1.27, and 1.29,
      respectively, and indicate increases in modality selectivity (MSI>1). Improving
      the S/N ratio and modality selectivity of neurographic recordings is an important
      development to increase the utility of neural signals for understanding neural
      function and for use as feedback or control signals in neural prosthetic devices.

PMID- 11248347
TI  - Developmental changes in GABA transporter (GAT1 and GAT3) mRNA expressions in the
      rat olfactory bulb.
AB  - Developmental expressions of GABA transporters 1 and 3 (GAT1 and GAT3) were
      investigated in the rat olfactory bulb by using in situ hybridization
      histochemistry. We found that the expression of GAT1 and GAT3 mRNAs was
      dramatically changed in the granule cell layer (GCL), external plexiform layer
      (EPL) and glomerular layer (GL) during postnatal development. Among bulbar
      neurons, granule cells and periglomerular cells are GABAergic and they are
      localized in the GCL and GL, respectively. In the EPL, granule cells make
      GABAergic synapses with mitral cell dendrites. Thus, the changes seen in the GCL,
      EPL and GL seemed related to the development of the GABAergic system in the
      olfactory bulb. On the whole, our results demonstrated that expression patterns
      of GAT1 and GAT3 mRNAs have become similar to adult patterns on postnatal day 14
      (P14), suggesting that GABA transporters may play a pivotal role in GABAergic
      neurotransmission after P14. However, expression patterns of GAT1 and GAT3 mRNAs
      in early postnatal days were quite distinct from those in adulthood. For example,
      in the GCL, immature granule cells already exhibited strong levels of GAT1 mRNA
      on P1 and the expression level was higher than that of granule cells in
      adulthood. GAT3 mRNA was strongly expressed in presumable radial glial cells
      surrounding the subependymal layer. In the EPL, few signals for the two
      transcripts were detected on P1 but they were markedly increased by P14. Our
      results indicate that GAT1 and GAT3 may play important roles in the development
      of the GABAergic system in the olfactory bulb.

PMID- 11248348
TI  - Prenatal alcohol exposure retards the migration and development of serotonin
      neurons in fetal C57BL mice.
AB  - Incomplete neural tube fusion (iNTF), induced by alcohol, in midline floor and
      roof plates was found in our recent study. In this study, serotonin (5-HT)
      neurons, known to be born entirely in the midline raphe at brainstem, were
      examined during their development with fetal alcohol exposure. Weight-matched
      C57BL mice pregnant dams were divided into three groups on E8: one received
      ethanol via a chocolate Sustacal liquid diet providing 20% ethanol-derived
      calories as the sole source of nutrients (ALC); the second received an isocaloric
      Sustacal liquid diet and was pair-fed to individual dams in the ethanol-fed group
      (PF); the third was fed ad lib rat chow (Chow). Fetal brains were obtained on E15
      and were processed for immunostaining of 5-HT and its trophic factor, S100 beta.
      The ascending 5-HT neurons, in normal development, appear bilaterally near
      midline on E12, and by E15, as seen in chow and PF groups, migrate from the
      midline germinal zone laterally and dorsally to their final position with rich
      fibers. In contrast, in the E15 ALC group, many 5-HT-im neurons were found
      remaining in the midline germinal region or had migrated, but with under
      differentiated, sparse fibers. There were 20--30% fewer 5-HT-im neurons in ALC as
      compared to PF and Chow. In addition, the number of S100 beta cells was less in
      ALC as compared with PF and Chow groups. No difference was found between PF and
      Chow in number of 5-HT-im or S100 beta-im cells. The 5-HT neurons found
      compromised in migration and differentiation may, in part, stem from failure of
      access to floor plate or midline tissue induction and the insufficient support by
      S100 beta. As 5-HT neurons have been implicated for signaling brain maturation,
      fewer 5-HT neurons may have lasting effects on the development of brain or, if
      persistent in the adult, profoundly affect adult brain function.

PMID- 11248349
TI  - Laminar distribution of cholinergic- and serotonergic-dependent plasticity within
      kitten visual cortex.
AB  - Both cholinergic and serotonergic modulatory projections to mammalian striate
      cortex have been demonstrated to be involved in the regulation of postnatal
      plasticity, and a striking alteration in the number and intracortical
      distribution of cholinergic and serotonergic receptors takes place during the
      critical period for cortical plasticity. As well, agonists of cholinergic and
      serotonergic receptors have been demonstrated to facilitate induction of long
      term synaptic plasticity in visual cortical slices supporting their involvement
      in the control of activity-dependent plasticity. We recorded field potentials
      from layers 4 and 2/3 in visual cortex slices of 60--80 day old kittens after
      white matter stimulation, before and after a period of high frequency stimulation
      (HFS), in the absence or presence of either cholinergic or serotonergic agonists.
      At these ages, the HFS protocol alone almost never induced long-term changes of
      synaptic plasticity in either layers 2/3 or 4. In layer 2/3, agonist stimulation
      of m1 receptors facilitated induction of long-term potentiation (LTP) with HFS
      stimulation, while the activation of serotonergic receptors had only a modest
      effect. By contrast, a strong serotonin-dependent LTP facilitation and
      insignificant muscarinic effects were observed after HFS within layer 4. The
      results show that receptor-dependent laminar stratification of synaptic
      modifiability occurs in the cortex at these ages. This plasticity may underly a
      control system gating the experience-dependent changes of synaptic organization
      within developing visual cortex.

PMID- 11248350
TI  - The role of calcium signaling in early axonal and dendritic morphogenesis of rat
      cerebral cortex neurons under non-stimulated growth conditions.
AB  - The effects of depolarizing stimuli on neurite outgrowth have been shown to
      depend on an influx of extracellular calcium. However, the role of calcium under
      non-stimulated growth conditions is less well established. Here we investigated
      the contribution of calcium signaling to early neuronal morphogenesis of rat
      cerebral cortex neurons at three levels by blocking L-type voltage sensitive
      calcium channels, by depleting intracellular calcium or by blocking myosin light
      chain kinase. Detailed quantitative morphological analysis of neurons treated for
      1 day revealed that depletion of intracellular calcium strongly decreased the
      density of filopodia, arrested axonal outgrowth and strongly decreased dendritic
      branching. Preventing calcium influx through L-type voltage sensitive calcium
      channels and blocking of myosin light chain kinase activity selectively decreased
      dendritic branching. Our observations support an essential role for basal
      intracellular calcium levels in axonal elongation. Furthermore, under non
      stimulated conditions calcium entry through L-type voltage sensitive calcium
      channels and myosin light chain kinase play an important role in dendritic
      branching.

PMID- 11248351
TI  - Transient expression of P2X(1) receptor subunits of ATP-gated ion channels in the
      developing rat cochlea.
AB  - The expression pattern of the ATP-gated ion channel P2X(1) receptor subunit was
      studied in the developing rat cochlea by riboprobe in situ hybridisation and
      immunohistochemistry. Embryonic (E12, E14, E16 and E18) and postnatal (P0, P2,
      P4, P6, P10 and adult) rat cochleae were examined. Both mRNA and protein
      localisation techniques demonstrated comparable P2X(1) receptor expression from
      E16 until P6 but this expression was absent at later developmental stages. P2X(1)
      receptor mRNA expression was localised within the otic capsule and associated
      mesenchyme (from E16 to P6), spiral limbus (from P0 to P6) and within the spiral
      ligament adjacent to the insertion of Reissner's membrane (from P2 to P6). P2X(1)
      receptor protein had a similar distribution based upon immunoperoxidase
      localisation. P2X(1) receptor-like immunoreactivity was detected in the otic
      capsule and the surrounding mesenchyme (from E16 to P6), spiral limbus (from P0)
      and epithelial cells of Reissner's membrane (from P2 to P6). The spiral ganglion
      neurones showed the earliest P2X(1) receptor expression (from E16 to P6). This
      became associated with immunolabelling of their afferent neurite projections to
      the base of the developing inner and outer hair cells (observed from E18 and
      peaking at P2). Immunolabelling of the efferent nerve fibres of the
      intraganglionic spiral bundle (from E18 to P6) within the spiral ganglion was
      also observed. The results suggest that ATP-gated ion channels assembled from
      P2X(1) receptor subunits provide a signal transduction pathway for development of
      afferent and efferent innervation of the sensory hair cells and purinergic
      influence on cochlear morphogenesis.

PMID- 11248353
TI  - Immunolocalization of the calcium binding S100A1, S100A5 and S100A6 proteins in
      the dog cochlea during postnatal development.
AB  - The immunolocalization of three members of the S100 calcium-binding protein
      family was investigated in the dog cochlea during normal postnatal development.
      Sections of decalcified and paraffin-embedded cochleae from 16 beagle puppies
      aged from birth to 3 months were treated with polyclonal antisera raised against
      the human recombinant S100A1, S100A5, and S100A6 proteins. At birth, in the dog
      cochlea, S100A1 was expressed in the immature Deiter's cells, and slightly in the
      pillar cells. From the second week, S100A1 was detected in the supporting
      structures of the organ of Corti, i.e. the Deiter's, the pillar, the border, and
      the Hensen's cells, and in the reticular membrane. From birth onwards, S100A5
      remained a neuronal-specific protein, only located in a subpopulation of neurons
      in the spiral ganglion. S100A6 was not expressed at birth. From the second week
      of life, the Schwann cells and nerve sheaths in the modiolus, in the spiral
      ganglion, and running in the direction of the organ of Corti exhibited S100A6
      labeling. From the 12th postnatal day, some scattered intermediate cells started
      to express S100A6 protein in the stria vascularis. The number of labeled
      intermediate cells increased during the third week. At adult stage, the
      intermediate cells were S100A6-stained with cytoplasmic labeling throughout the
      stria vascularis from the base to the apex of the cochlea. None of the other
      cochlear structures expressed the S100 proteins under study during the postnatal
      development of the dog cochlea. The S100A1, S100A5, S100A6 immunostaining was
      limited to specific cell types in dog cochlea. These S100 proteins were useful
      markers in the study of supporting cells, neurons, nerve fibers sheaths and stria
      vascularis (S100A6) during the normal postnatal development of the dog cochlea.

PMID- 11248352
TI  - Comparison of ganglioside profiles in nuclei and whole cells of NG108-15 and NG
      CR72 lines: changes in response to different neuritogenic stimuli.
AB  - The plasma and nuclear membranes of neural cells have been shown to express
      gangliosides to a limited extent before, and at increasing levels during,
      differentiation. Recent studies employing qualitative cytochemistry have shown
      that GM1 expression in particular is significantly elevated in both membranes by
      specific neuritogenic agents. The present study provides a more complete
      description of ganglioside patterns of the 2 membranes of NG108-15 cells and a
      mutated form of the latter lacking gangliotetraose gangliosides. Nuclei of wild
      type NG108-15 cells were found to contain predominantly GM1 and GD1a, whereas
      whole cells had those in addition to substantial amounts of GM2 and GM3. GM1 and
      GD1a levels increased 2--3.5-fold in both whole cells and nuclei following
      axonogenic stimulation, but changed little in response to dendritogenic agents.
      GM2 expression, limited to the plasma membrane, showed little if any change with
      axonogenic stimuli but a 1.5--2-fold increase following treatment with
      dendritogenic agents. GM3 resembled GM2 in being virtually absent from the
      nuclear membrane, while its presence in the plasma membrane showed only modest
      change at most with any of the stimuli. The gangliotetraose ganglioside-deficient
      mutant cell line, NG-CR72, had significantly higher basal levels of GM2 in the
      plasma membrane compared to wild type NG108-15 cells, and this level increased
      significantly on treatment with dendritogenic agents. Basal GM3 levels were
      greatly reduced in the mutant cells and changed little with any of the stimuli.
      As expected, nuclei of NG-CR72 cells were virtually devoid of gangliosides. These
      mutant cells were previously shown to extend well defined dendritic neurites but
      were incapable of forming stable axonal processes. This study thus demonstrates
      major differences in the ganglioside content of wild type and mutated NG108-15
      cells and their nuclei, and in their response to different neuritogenic stimuli.

PMID- 11248354
TI  - Progressive atrophy of cerebellar Purkinje cell dendrites during aging of the
      heterozygous staggerer mouse (Rora(+/sg)).
AB  - Staggerer (Rora(sg/sg)) is an autosomal mutation in an orphan nuclear hormone
      receptor gene, RORalpha, that acts intrinsically within the Purkinje cells and
      causes dysgenesis of the cerebellar cortex. Purkinje cell number is severely
      reduced, and the surviving cells are small with poorly developed dendrites. In
      contrast, the cytoarchitecture of the cerebellar cortex of the heterozygous
      staggerer (Rora(+/sg)) appears to be normal. However, quantitative studies have
      revealed a premature loss of Purkinje cells with advancing age. Most of the loss
      (25--30%) is complete by 13 months with little change thereafter. To address the
      question of whether all Purkinje cells, even the surviving ones, are affected by
      aging even though their cell bodies remain intact, we studied the evolution with
      age of the dendritic arbor through a semi-quantitative analysis of Golgi
      impregnated Purkinje cells. A total of ten different morphological parameters
      were measured in 4-, 12- and 22-month-old wild type and heterozygous Rora(+/sg)
      mice. While the effects of the aging process are apparent in the wild type
      cerebellum, they are considerably accelerated in the Rora(+/sg) mouse. By 12
      months the Rora(+/sg) Purkinje cell dendrite is as atrophic as a wild type
      dendrite from a 22-month-old and the dendritic regression continues well beyond
      the period of cell death in the heterozygous Rora(+/sg) mouse.

PMID- 11248355
TI  - Developmental changes of (3)H-labelled mu-opioid receptors in brainstems of intra
      uterine growth-restricted rats.
AB  - The opioid mu-system is involved in brainstem-mediated respiratory control.
      Infants with intra-uterine growth restriction (IUGR) have more respiratory
      disorders in the early postnatal period. Using [(3)H]DAGO, a mu-selective ligand,
      and a computer-based image analysis of autoradiography, we compared the ontogeny
      and distribution of mu-opioid binding sites in the brainstem of IUGR and control
      rats in utero (E21), at birth (P0) and on postnatal days 1 (P1), P7, P10, P14 and
      P21. The ontogeny pattern was found to be similar in both groups. The density of
      the binding sites, which was low in E21, increased at P0, slightly declined at P1
      and remained relatively constant thereafter. The distribution of DAGO-binding
      sites, also similar in both groups, was heterogeneous and was much denser in the
      dorsal areas of medulla and pons. In particular, binding sites were highly
      concentrated in nuclei involved in the cardio-respiratory function. However, DAGO
      binding density was higher at all ages (except for P0 and P1) in IUGR than in
      control rats. Taken together, these results give at least a partial explanation
      for the effects of IUGR which lowers the Apgar score at birth and raises the
      incidence of respiratory disorders in infants.

PMID- 11248356
TI  - Maternal and perinatal brain aromatase: effects of dietary soy phytoestrogens.
AB  - Phytoestrogens are extensively investigated for their potential to prevent many
      hormone-dependent cancers and age-related diseases, however little is known about
      their effects in brain. Brain aromatase and plasma phytoestrogen levels were
      determined in Sprague-Dawley rats fed a phytoestrogen-rich diet during
      pregnancy/lactation. Ingested phytoestrogens cross the placenta and become
      concentrated in maternal milk as evident from high infantile plasma
      concentrations. Dietary phytoestrogens, however, do not alter brain aromatase
      during pregnancy/lactation or perinatal development.

PMID- 11248357
TI  - Do recurrent febrile convulsions decrease the threshold for pilocarpine-induced
      seizures? Effects of nitric oxide.
AB  - The aim of the study was to determine whether (1) number of febrile convulsions
      is a predictor of development of temporal lobe epilepsy, (2) the susceptibility
      of rats to pilocarpine-induced seizures is increased due to febrile convulsions
      and (3) nitric oxide is a mediator in the pathogenesis of febrile convulsions.
      Rat pups were exposed to single or multiple hyperthermic seizures. Subconvulsant
      doses of pilocarpine (100 mg/kg and 150 mg/kg) were injected intraperitoneally to
      these rats at 60--70 days of age. Also L-arginine was applied to some rats before
      a single hyperthermic seizure. We found that risk of future epilepsy increases
      parallel to the number of febrile convulsions and nitric oxide does not have a
      pathogenetic role at given doses.

PMID- 11248358
TI  - Localization of low affinity nerve growth factor receptor in the rat inferior
      olivary complex during development and plasticity of climbing fibres.
AB  - The rat olivocerebellar pathway has a precise topography from an inferior olive
      (IOC) to Purkinje cells in the contralateral hemicerebellum. While its
      development and plasticity have been documented, the molecular mechanisms
      underlying these events are not fully elucidated. Neurotrophins are a family of
      growth factors with diverse roles in development and neuronal plasticity, acting
      through a two-receptor system, including a low affinity receptor (LNGFR) which
      binds all neurotrophins with similar affinity. Since neurotrophins are present in
      the cerebellum during early postnatal development when LNGFR is synthesized in
      the IOC, they may act as target-derived trophic agents for climbing fibres during
      development and plasticity. To assess this, standard immunohistochemistry was
      used to document the distribution of LNGFR in the rat IOC during climbing fibre
      development and until cerebellar development was complete at postnatal day 28
      (P28). LNGFR immunoreactivity (LNGFR-IR) was detected in the IOC from P0 until
      P15, however after P7 it diminished in intensity and distribution, a change which
      indicates a relationship between cerebellar neurotrophins and climbing fibre
      development. After denervation of the left hemicerebellum, there was an apparent
      increase in inferior olivary LNGFR-IR that was concurrent with climbing fibre re
      innervation. Thus the results of this study support the hypothesis that
      neurotrophins are involved in climbing fibre development and suggest a possible
      contribution to the plasticity of the olivocerebellar pathway.

PMID- 11248359
TI  - Genetic risks of antiviral nucleoside analogues--a survey.
AB  - The available informations on the genotoxic effects in experimental systems of
      the antiherpesvirus nucleosides aciclovir, penciclovir, ganciclovir, brivudine
      and cidofovir as well as of the antiretrovirals zidovudine (AZT), lamivudine,
      zalcitabine (ddC), didanosine and stavudine are reviewed. Furthermore, data on
      carcinogenic activity of these drugs in laboratory rodents are compiled. Most
      nucleoside analogue antivirals induce chromosomal aberrations but are inactive in
      gene mutation assays. Carcinogenicity findings in mice and rats are variable but
      clearly positive for AZT and ddC. The possible mechanisms by which these agents
      may cause damage in the genetic information are still largely hypothetical, and
      experimental findings do not permit relevant extrapolations to the situation in
      man. There is no conclusive evidence that any of the drugs caused tumours in
      humans. The use of nucleoside analogues in antiviral therapy remains a pragmatic
      option that seems justified by risk/benefit assessment.

PMID- 11248360
TI  - Vitamin E as treatment for chronic hepatitis B: results of a randomized
      controlled pilot trial.
AB  - BACKGROUND AND AIMS: Interferon-alpha treatment has been the treatment of choice
      for chronic hepatitis with unpredictable results. Recently, Lamivudine has been
      licensed for use against HBV infection with good results. Unfortunately,
      recurrence of viremia after lamivudine withdrawal is common and prolonged
      treatment can induce the emergence of resistant mutant strains. It has been shown
      that vitamin E can increase the host immune response, and this may provide
      protection against infectious diseases. METHODS: We evaluated vitamin E
      supplementation as therapy for chronic hepatitis B in a pilot study including 32
      patients. Patients were randomly allocated to receive vitamin E at the dose of
      300 mg twice daily for 3 months (15 patients) or no treatment (17 patients). They
      were seen monthly during the first 3 months and thereafter quarterly for
      additional 12 months. RESULTS: The two groups were comparable at enrollment. At
      the end of the study period, alanine aminotransferase (ALT) normalization was
      observed in 7 (47%) patients in vitamin E group and only in 1 (6%) of the
      controls (P=0.011); HBV-DNA negativization was observed in 8 (53%) patients in
      the vitamin E group as compared to 3 (18%) in the control group, respectively
      (P=0.039). A complete response (normal ALT and negative HBV-DNA) was obtained in
      7 (47%) patients taking vitamin E and in none of the controls (P=0.0019).
      CONCLUSION: Vitamin E supplementation might be effective in the treatment of
      chronic hepatitis B.

PMID- 11248362
TI  - Inhibition of the early phase of HIV replication by an isothiazolone, PD 161374.
AB  - A new class of substituted 2'-benzisothiazolone represented by PD 161374 was
      discovered with antiviral activity against retroviruses similar to previously
      described nucleocapsid inhibitor PD 159206 (DIBA-4). In T cell culture, the 50%
      inhibitory concentrations (EC(50)) of PD 161374 and PD 159206 were on average 2.5
      microM (ranges of 1.2-13.5 microM) without any cytotoxic effect up to 100 microM.
      PD 161374 inhibited acute HIV infection and it was effective when added during
      the early phase of HIV infection. However, very modest effects were observed in
      chronically infected H9 cells and the HIV latency model line OM-10.1. Direct PCR
      analysis of infected cells demonstrated that PD 161374 delayed the appearance of
      completed HIV-cDNA products including 2LTR circles. Together all these results
      suggest that PD 161374 exerts its antiviral effect at pre-integration steps in
      the early phase of the virus life cycle. When combined with a protease inhibitor,
      PD 161374 did not show any antagonism and combination with a reverse
      transcriptase inhibitor (AZT) resulted in a synergistic effect.

PMID- 11248361
TI  - A comparison of oral and parenteral routes for therapeutic vaccination with HSV-2
      ISCOMs in mice; cytokine profiles, antibody responses and protection.
AB  - It is likely that recurrent infections with HSV-2 (or HSV-1) are influenced by
      local levels of immunity at mucosal surfaces, when virus reactivated from the
      latent state is infecting mucosal epithelial cells. Increasing the levels of
      cellular and humoral immunity through immunisation and maintaining such increased
      levels, may reduce establishment and spread of reactivated virus at the local
      site, thereby ameliorating recurrent disease symptoms. The use of HSV-2 antigens
      incorporated into immunostimulating complexes (ISCOMs) for immunisation of mice
      previously infected with HSV-2 was investigated in the present study.
      Prophylactic administration of HSV-2 ISCOM vaccine to mice elicits local antibody
      detectable in nasal washings, serum antibody and the presence of cytokines IL-2,
      IFN-gamma and IL-4 in supernatants from spleen cell cultures stimulated in vitro
      with HSV-2 antigens. Use of the same vaccine in mice infected previously with HSV
      2, results in increased levels of total and subclass serum ELISA antibody and
      also increased levels of serum neutralising antibody. Treatment of HSV-2 infected
      mice with the HSV-2 ISCOM vaccine also induces higher levels of the cytokines IL
      2, IFN-gamma and IL-4, in in vitro stimulated spleen cell cultures. Challenge
      with a lethal dose of HSV-1 showed that mice previously infected with HSV-2 and
      subsequently given two doses of HSV-2 ISCOMs vaccine were protected.

PMID- 11248363
TI  - Anti-herpesvirus activity of (1'S,2'R)-9-[[1',2'-bis(hydroxymethyl)-cycloprop-1'
      yl]methyl] x guanine (A-5021) in vitro and in vivo.
AB  - The novel nucleoside analog (1S',2R')-9-[[1',2'-bis(hydroxymethyl)cycloprop-1
      yl]methyl]guanine (A-5021) was previously shown to be a potent inhibitor of the
      replication of herpes simplex virus type 1 and 2 (HSV-1 and HSV-2) and varicella
      zoster virus (VZV), both in vitro and in vivo (J. Med. Chem. 41, 1284-1298;
      Antimicrob. Agents Chemother. 42, 1666-1670). Here we demonstrate that A-5021 is
      also a potent inhibitor of Epstein-Barr virus (EBV) and human herpes virus 6 (HHV
      6A and HHV-6B), but that the compound lacks activity against HHV-8. A-5021, in
      comparison to acyclovir, was also assessed for protective activity against HSV-1
      induced mortality in SCID mice. The compounds were administered at 50 mg/kg per
      day by subcutaneous injection for four consecutive days and treatment was
      initiated at either 2 h, 1 or 2 days post infection (p.i.). When administered
      from day 0 to 4 p.i., A-5021 conferred complete protection against the infection
      (as assessed at 22 days p.i.), whereas acyclovir delayed virus induced mortality
      by only 5 days. When treatment was begun on day 1 or 2, A-5021 still afforded
      marked protection against the infection, whereas acyclovir was virtually devoid
      of any activity under these conditions. Our data underline that A-5021 may offer
      great promise for the treatment of herpesvirus infections.

PMID- 11248364
TI  - The anti-herpesvirus activity of (1'S,2'R)-9-[[1',2'-bis(hydroxymethyl)-cycloprop
      1'-yl]methyl]guanine is markedly potentiated by the immunosuppressive agent
      mycophenolate mofetil.
AB  - Mycophenolic acid (MPA), the active form of the immunosuppressive agent
      mycophenolate mofetil (MMF), was found to markedly potentiate the anti
      herpesvirus activity of the novel anti-herpesvirus agent A-5021, (1'S,2'R)-9
      [[1',2'-bis(hydroxymethyl)cycloprop-1'-yl]methyl]guanine. For example, at a
      concentration of 1 microg/ml MPA, the activity of A-5021 against HSV-1, HSV-2 and
      TK(-) HSV-1 increased by a factor of 130, 14 and > or = 189, respectively.
      Exogenously added guanosine reversed this potentiating effect, suggesting that a
      depletion of the endogenous dGTP pools enhanced the inhibitory effect of the 5'
      triphosphate metabolite of A-5021 on the viral DNA polymerase. The combined
      effect of A-5021 and MPA on the growth of uninfected Vero cells was additive
      rather than synergistic. The combination of topically applied MMF (5%) with 0.05%
      A-5021 (a subactive concentration) completely protected against HSV-1-induced
      cutaneous lesions in hairless mice, whereas therapy with either compound used
      alone had no protective effect. These findings may have implications for those
      transplant recipients that receive MMF as (part of) their immunosuppressive
      therapy and that develop intercurrent herpesvirus infections for which they need
      treatment.

PMID- 11248365
TI  - Modification of AMPA receptor clustering regulates cerebellar synaptic
      plasticity.
AB  - Cerebellar long-term depression (LTD) induced at parallel fiber-Purkinje neuron
      synapses is proposed to underlie certain types of motor learning. alpha-Amino-3
      hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors, which mediate chemical
      transmission in these synapses, are clustered on the postsynaptic membrane. By
      increasing local density of the receptors, clustering is believed to increase
      synaptic efficacy. This article focuses on molecular mechanisms regulating the
      synaptic AMPA receptor clustering in Purkinje cells, which could underlie the
      expression of cerebellar LTD. Synaptic AMPA receptor clusters in dendritic spines
      of Purkinje cells are disrupted upon protein kinase C (PKC)-mediated
      phosphorylation of serine 880 in the C-terminal domain of GluR2. Phosphorylation
      of this residue causes significant reduction in the affinity of GluR2 C-terminal
      tail for glutamate receptor interacting protein (GRIP), a molecule known to be
      crucial for AMPA receptor clustering. Consequently, AMPA receptors on the
      synaptic membrane are destabilized and internalized by endocytosis. Based on
      these findings, a model for the expression of cerebellar LTD is proposed, in
      which a decrease in the number of postsynaptic AMPA receptors, initiated by
      phosphorylation of GluR2 serine 880, is the major mechanism underlying cerebellar
      LTD.

PMID- 11248366
TI  - Optical imaging reveals cation--Cl(-) cotransporter-mediated transient rapid
      decrease in intracellular Cl(-) concentration induced by oxygen--glucose
      deprivation in rat neocortical slices.
AB  - In brain slices from young (postnatal day (P) 10--15) rat somatosensory cortex,
      real-time neuronal intracellular Cl(-) concentration ([Cl(-)](i)) recordings were
      made by an optical technique measuring 6-methoxy-N-ethlquinolinium iodide (MEQ)
      fluorescence. Oxygen--glucose deprivation (in vitro model of ischemia) induced a
      long-lasting [Cl(-)](i) increase preceded by a rapid, transient [Cl(-)](i)
      decrease that could not be inhibited by blockers of Cl(-) pumps, Cl(-) channels,
      or Cl(-) antiporters, but was sensitive to cation-Cl(-) cotransporter inhibitors
      (bumetanide and furosemide). Use of low external Na(+) or high external K(+)
      revealed that the Na(+),K(+)-2Cl(-) cotransporter was inhibited by bumetanide and
      furosemide, whereas the K(+)-Cl(-) cotransporter was preferentially inhibited by
      furosemide under our experimental conditions. With a reduced inward driving force
      for Na(+) (reducing Na(+),K(+)-2Cl(-) cotransport), the transient [Cl(-)](i)
      decrease was only rarely induced by oxygen-glucose deprivation. In contrast, with
      a reduced outward driving force for K(+) (reducing K(+)-Cl(-) cotransport), the
      transient [Cl(-)](i) decrease still occurred. These results suggest that the
      transient [Cl(-)](i) decrease was primarily mediated by a rapid inhibition of the
      inwardly directed Na(+),K(+)-2Cl(-) cotransporter. Reverse transcriptase
      polymerase chain reaction (RT-PCR) experiments suggested that the isoform
      involved is NKCC1. We hypothesize that the initial rapid Cl(-) efflux might
      effectively delay the irreversible Cl(-) influx that mediates neuronal injury.

PMID- 11248367
TI  - The involvement of glial cells in the development of morphine tolerance.
AB  - Glial response to chronic morphine treatment was examined by immunohistochemistry
      of glial fibrillary acidic protein (GFAP), a specific marker for astroglial
      cells. Systemic administration of morphine (50 mg/kg, i.p.) once daily for 9
      consecutive days led to significant increase in GFAP immunostaining density in
      the spinal cord, posterior cingulate cortex and hippocampus but not in the
      thalamus. This increase was attributed primarily to hypertrophy of astroglial
      cells rather than their proliferation or migration. When chronic morphine (20
      microg/2 microl, i.t.) was delivered in combination with fluorocitrate (1 nmol/1
      microl, i.t.), a specific and reversible inhibitor of glial cells, spinal
      tolerance to morphine analgesia was partly but significantly attenuated as
      measured by behavioural test and the increase in spinal GFAP immunostaining was
      also greatly blocked. The present investigation provides the first evidence for
      the role of glial cells in the development of morphine tolerance in vivo.

PMID- 11248368
TI  - The role of desensitisation in decay time of miniature endplate currents in frogs
      Rana ridibunda and Rana temporaria.
AB  - A new comparative characteristic of endplate microphysiology has been introduced.
      It is the feasibility of receptors to become desensitised as demonstrated on two
      frog species, Rana temporaria and Rana ridibunda: the decay times (tau(MEPC)) of
      single quantum miniature endplate currents (MEPCs) in the sartorius muscles of
      both species were about 1 ms and were not affected by the desensitisation
      promoting agent proadifen when AChE was active. However, when the desensitisation
      was induced by anticholinesterase neostigmine and promoted by proadifen, the
      prolongation of tau(MEPC) from 1 ms was almost twice as great in Rana temporaria
      (tau(MEPC) = 4.4 ms) than in Rana ridibunda (tau(MEPC) = 3.1). This indicates
      that desensitisation reduces the number of available receptors and lowers the
      number of available ACh molecules for repetitive binding by trapping them by
      desensitised, high-affinity receptors significantly more in Rana ridibunda than
      in Rana temporaria. The application of proadifen, a promoter of desensitisation,
      decreased the prolongation of MEPCs in both species, but this shortening was more
      rapid in Rana ridibunda than in Rana temporaria. It is concluded that the
      desensitisation-induced reduction in the density, and the number of postsynaptic
      receptors is significantly higher at Rana ridibunda than in Rana temporaria
      endplates.

PMID- 11248369
TI  - Effects of previous noxious stimulus applied to remote areas on noxious stimulus
      evoked c-Fos expression in the rat trigeminal nucleus caudalis.
AB  - Noxious stimulus-evoked c-Fos expression in the spinal dorsal horn is modulated
      by noxious stimuli applied previously to remote areas of the body. To confirm the
      existence of such modulation in c-Fos expression in the trigeminal system,
      changes in c-Fos expression in the trigeminal nucleus caudalis induced by
      formalin injection into the rat whisker pad were examined by previously injecting
      formalin into different areas (contralateral whisker pad, ipsilateral or
      contralateral forepaw) of the body. Formalin injection-evoked c-Fos expression in
      this nucleus was significantly reduced by previous formalin injection into the
      contralateral whisker pad or ipsilateral forepaw but not into the contralateral
      forepaw. The interval between the two injections of formalin that produced a
      maximal reduction of formalin injection-evoked c-Fos expression was 1 h, and the
      reduction of c-Fos expression was less when the interval of the two noxious
      stimuli was longer or shorter than 1 h. These results suggested that noxious
      stimulus-evoked c-Fos expression in the trigeminal nucleus caudalis is reduced by
      noxious stimulus applied previously to remote areas, and the reduction is
      dependent on the area of previous noxious stimulation and interval between the
      two noxious stimuli.

PMID- 11248370
TI  - Dynamic properties, interactions and adaptive modifications of vestibulo-ocular
      reflex and optokinetic response in mice.
AB  - Dynamic properties of horizontal vestibulo-ocular reflex (VOR) and optokinetic
      response (OKR) were studied in mice. The VOR was examined in the dark (VORD), in
      the light (VORL) and in the condition in which most of the visual field moves
      synchronously with the head motion (VORF). A mouse and/or a surrounding screen
      with vertical stripes was rotated sinusoidally, and the gain and phase of eye
      movements were measured in wide dynamic stimulation ranges. The working
      conditions of VOR and OKR were supplementary; OKR worked at low speeds of head
      turn and VOR at high speeds. Examination of VORL and VORF revealed non-linear
      interaction of VOR and OKR. The continuous sinusoidal head oscillation coupled
      with the in-phase or the out-of-phase oscillation of the surrounding screen,
      decreased or increased the VORD gain, and increased or decreased the VORD phase
      lead, respectively. Continuous oscillation of the surrounding screen increased
      the OKR gain and decreased the phase delay. These changes of VOR and OKR work to
      reduce the retinal slip. The present study provides fundamental information
      concerning the dynamic properties of VOR and OKR and the nature of their adaptive
      modifications in mice, which have been extensively used in genetic manipulation
      recently.

PMID- 11248371
TI  - Expression of human brain carboxypeptidase B, a possible cleaving enzyme for beta
      amyloid precursor protein, in peripheral fluids.
AB  - Human brain carboxypeptidase B (HBCPB) is a novel brain protease that processes
      native brain beta-amyloid precursor protein (APP) in vitro. Immunoblot analysis
      of human serum and cerebrospinal fluid (CSF) using anti C14-module antibody,
      which recognizes the C-terminal peptide unique to HBCPB, detected the 30 and 40
      kDa immunoreactive bands. Analysis of HBCPB prepared from both serum and CSF
      demonstrated proteolytic activities for brain APP. Protease inhibitor spectrum
      analysis also supports that these bands correspond to the mature form and and
      prepro form of HBCPB, respectively. As is the case in brain parenchyma, the
      prepro-form is dominant in CSF. In serum, however, the majority of HBCPB exists
      in the mature form, possibly due to an abundant trypsin-like proteolytic activity
      in serum. HBCPB expressed in serum and CSF, therefore, may have a significance as
      a peripheral marker of the brain protease, which participates in APP processing
      in human brain.

PMID- 11248372
TI  - Differential sensitivity to NaCl for inhibitors and substrates that recognize
      mutually exclusive binding sites on the neuronal transporter of dopamine in rat
      striatal membranes.
AB  - Addition of NaCl (90--290 mM) to a 10 mM Na(+) medium did not significantly
      modify B(max) and K(d) values for [3H]mazindol binding to the dopamine neuronal
      transporter (DAT) studied on rat striatal membranes at 20 degrees C. Addition of
      NaCl differentially affected the ability of other uptake inhibitors and
      substrates to block the [3H]mazindol binding. Ratios of 50% inhibiting
      concentrations calculated for 290 and 90 mM NaCl allowed to distinguish three
      groups of agents: substrates which were more potent in the presence of 290 mM
      NaCl (group 1; ratio < 1) and two groups of uptake inhibitors displaying ratio
      values either ranging around two (group 2: WIN 35,428, cocaine, methylphenidate,
      pyrovalerone) or close to unity (group 3: BTCP, mazindol, benztropine,
      nomifensine). However, agents from these three groups recognize mutually
      exclusive binding sites since in interaction studies the presence of WIN 35,428
      (group 2) or mazindol (group 3) increased the 50% inhibiting concentrations of D
      amphetamine (group 1) and WIN 35,428 on the [3H]mazindol binding to theoretical
      values expected for a competition of all of these compounds for the same binding
      domain on the DAT.

PMID- 11248373
TI  - Modulation by cGMP of the voltage-gated currents in newt olfactory receptor
      cells.
AB  - Effects of cGMP on voltage-gated currents in the somatic membrane of isolated
      newt olfactory receptor cells were investigated using the whole-cell mode of the
      patch-clamp technique. Under voltage clamp, membrane depolarization generated
      time- and voltage-dependent current responses, a transient inward current and a
      sustained outward current. When cGMP or a membrane permeant analog of cGMP, 8-p
      chlorophenylthio-cGMP (CPT-cGMP), was applied to the recorded cell, the amplitude
      of the transient inward current increased markedly, but that of the sustained
      outward current did not change significantly. When each current was isolated by
      pharmacological agents, 0.1 mM CPT-cGMP increased the peak amplitude of a Na(+)
      current (I(Na)) by approximately 40%, a T-type Ca(2+) current (I(Ca,T)) by
      approximately 40%, and an L-type Ca(2+)current (I(Ca,L)) by approximately 10%;
      however it did not change significantly the amplitude of a delayed rectifier K(+)
      current (I(K)). A selective cGMP-dependent protein kinase inhibitor, KT5823,
      blocked the enhancement by cGMP of I(Na) and I(Ca,T), suggesting that cGMP
      increases these currents via cGMP-dependent phosphorylation. Under current-clamp
      conditions, application of CPT-cGMP lowered the current threshold of action
      potentials induced by current injection, and increased the maximum spike
      frequency in response to strong stimuli. We suggest that cGMP may lower the
      threshold in olfactory perception by decreasing the current threshold to generate
      spikes, and also prevent the saturation of odor signals by increasing the maximum
      spike frequency.

PMID- 11248374
TI  - Progressive cortical atrophy after forebrain ischemia in diabetic rats.
AB  - The morphological changes in the brain of diabetic rats were examined up to 8
      weeks after transient forebrain ischemia produced by transient occlusion of both
      carotid arteries. Using histochemistry, we also examined the extent and rate of
      development of atrophic changes in the brain, appearance of astrocytes, activated
      microglia, and glucose transporter 1 (GLUT1) in streptozotocin-treated rat brains
      after forebrain ischemia. Atrophic changes appeared in the hippocampus in both
      non-diabetic-- and diabetic--ischemic groups 4 weeks after ischemia. In diabetic-
      ischemic rats, the atrophic changes were more severe and progressed more rapidly
      in the hippocampus, and were also observed in the frontal, temporal and parietal
      cortices, but not in any cortical areas of the non-diabetic--ischemic rats and
      non-ischemic--diabetic rats. We observed reduced density of GLUT1 in all cortical
      regions and hippocampus in ischemic-diabetic rats at 4--8 weeks, when the number
      of activated microglias and astroglias increased in all cortical regions.
      Although severe atrophic changes were observed in the gray matter, no serious
      injury was noted in the white matter in the diabetic-ischemic group. Our results
      indicate that brain ischemia in the presence of diabetes causes more severe late
      onset damage culminating in brain atrophy, compared with non-diabetics.

PMID- 11248375
TI  - Spatiotemporal distribution of GAP-43 in the developing rat spinal cord: a
      histological and quantitative immunofluorescence study.
AB  - In the rat spinal cord we studied developmental changes in spatiotemporal
      expression of the growth-associated protein GAP-43, which is known to play an
      important role in neural development, axonal regeneration, and modulation of
      synaptic function. GAP-43 was expressed predominantly in the white matter at
      embryonic day 13 to postnatal day 7, evenly in the white and gray matter at the
      2nd to the 3rd postnatal week, and predominantly in the gray matter after the 5th
      postnatal week. The shifting of predominance was quantitatively assessed. On the
      basis of histological findings and quantitative assessment of GAP-43
      immunoreactivity, it appears likely that the development proceeds from the phase
      of mostly axonal elongation during the embryonic period and the 1st postnatal
      week, via the phase of axonal elongation and formation of end arbors and synaptic
      organization during the 2nd to the 4th postnatal week, to the phase of final
      maturation of synaptic organization. GAP-43 was continuously expressed through
      adulthood in neuropil of the gray matter, the pyramidal tract, and the dorsal
      portion of the lateral funiculus that was identified as serotonergic by confocal
      laser scanning microscopic studies. The continuous expression may imply perpetual
      remodeling in these structures even in adulthood.

PMID- 11248376
TI  - The properties of convergence eye movements evoked from the rostral and caudal
      lateral suprasylvian cortex in the cat.
AB  - Convergence eye movements were evoked in the lateral suprasylvian cortex (LS
      cortex) in the cat. Three effective regions were found: the rostral and caudal
      parts of the postero-medial LS cortex (the PMLS) and the rostral part of the
      postero-lateral LS cortex (the PLLS). These three areas represent the central and
      paracentral visual fields in the published retinotopic map (Palmer et al., 1978).
      Convergence eye movements evoked from the caudal PMLS were divided into two
      groups based on their latencies; the short-latency components (SLC) and long
      latency components (LLC). The SLC and the LLC had differences in their symmetry
      of right and left eye movements during vergence eye movement. The SLC had
      symmetric right and left eye components and the LLC had dominant contralateral
      eye components. In the rostral PMLS, latencies of evoked convergence eye movement
      were comparable to those of the caudal PMLS, but they did not divided into two
      groups. Convergence eye movements evoked from the PLLS had longer latencies than
      those from the PMLS and asymmetric right and left eye components. It is suggested
      that different subregions in the LS cortex contribute to the control of
      convergence eye movement, playing different roles.

PMID- 11248377
TI  - Do beef cattle react consistently to different handling situations?
AB  - Beef cattle responses to handling depend partly on the genetic characteristics of
      the animals. However, the various methods used in order to assess these responses
      differ to a great extent. The purpose of this work is to study the relationship
      between two different situations extensively used to evaluate cattle reactions to
      handling. Moreover, the genetic variability of cattle responses to these two
      handling situations was investigated. Behavioural reactions of 245 Limousine
      heifers, from 10 sires, were evaluated both in a docility test and in a crush
      test. In the docility test, a human tried to lead and then to maintain the animal
      in the corner of a pen during 30 consecutive seconds, with a maximum duration of
      the test of 3.5min. A docility score summarised the animal's behavioural
      reactions to the test. The crush test procedure consisted of social isolation of
      the animal in a crush, with the head maintained in a head gate (5min), then
      exposure to a stationary human (30s), and finally stroking on the forehead (30s).
      An agitation index for each part of this test was computed from PCA analyses
      based on agitation behaviours. Sire effect was significant for every part of both
      tests (P<0.05). Heifers' behavioural responses to the docility test were
      significantly correlated with their responses to the crush test, when the animals
      were in isolation (r=0.29; P<0.001), when the human stood motionless in front of
      the animals (r=0.37; P<0.001), and when the human stroked them (r=0.28; P<0.001).
      Sires' behavioural reactions to the docility test (computed from their daughters'
      scores) were correlated with their reactions to the crush test only when the
      human was present, both when motionless (r=0.88; P<0.001) and when stroking the
      heifer (r=0.81; P<0.05). No relationship appeared between sires' behavioural
      reactions to the docility test and their responses to restraint in the crush when
      the human was absent (P=0.17). Furthermore, the crush test did not reveal the
      animals which presented aggressive reactions to handling in the docility test.
      The results exposed in this paper pointed out the existence of a general
      reactivity of beef cattle to handling, whether the animals are restrained or not,
      which appears influenced by the sire. Such reactivity is suggested to be mainly a
      consequence of the animals reactions to humans. The human environment needs to be
      precisely defined in the handling test procedures before using them as a
      selection criteria.

PMID- 11248378
TI  - Seasonal changes in circadian grazing patterns of Kerry cows (Bos Taurus) in semi
      feral conditions in Killarney National Park, Co. Kerry, Ireland.
AB  - Domestic cattle generally graze during the day although some night-time grazing
      also occurs. However, questions remain as to the effect of management on
      circadian grazing patterns. This study provides for the first time a
      quantification of seasonal, circadian and animal variation in grazing behaviour
      and grazing time in cattle in semi-wild conditions.The objectives of the study
      were to examine how daily grazing times and the temporal distribution of grazing
      activity changed with season and to examine the extent to which grazing patterns
      were influenced by day-length. A group of 12 heifers of the Kerry breed
      continuously grazed a lowland field of 4.7ha. The old permanent pasture sward was
      dominated by Holcus spp. and Agrostis spp. Feed availability was never limiting.
      Length and periodicity of grazing were recorded using vibracorders attached to
      the necks of seven animals.Results showed that daily grazing times remained
      constant over most of the grazing season (circa 10-11h per day), however, some
      variation occurred late in the season. The temporal distribution of grazing
      activity changed as the season advanced so that by October grazing patterns
      became significantly different to those of July. The time interval between
      grazing bouts at dawn and dusk decreased with decreasing day-length. An increased
      percentage of night-time grazing occurred at shorter day-lengths.It is concluded
      that there is a significant seasonal effect of day-length on temporal
      distribution of grazing activity with night-time grazing featuring more as day
      length decreases. The maintenance of similar total daily grazing times in the
      face of changing day-length (with the exception of late in the season) suggests
      that daily grazing times are a function of the attainment of a relatively
      constant nutritional requirement by the animal.

PMID- 11248379
TI  - Influence of environmental temperature on PGF(2alpha)-induced nest building in
      female pigs.
AB  - Domestic pigs build a maternal nest in the day preceding parturition. We have
      shown that prostaglandin F(2alpha) (PGF(2alpha)) induces nest building behaviour
      in non-pregnant pigs. The aim of this experiment was to examine the effects of
      different environmental temperatures on PGF(2alpha)-induced nest building. Data
      were collected from 9 Large White (LW) and 10 Large Black (LB) 8-9-month-old
      nulliparous sows (gilts). The pigs were housed in social groups between
      experiments and tested individually in pens (1.8mx1.8m) containing straw, within
      an environmentally controlled chamber. Pigs were habituated to the testing pens
      (maintained at 17 degrees C) and tested once at each of three temperatures (low,
      5 degrees C; moderate, 17 degrees C; high, 30 degrees C). During testing the
      temperature of the chamber was adjusted at 09.00h and had reached set point
      by10.00h. The pigs were injected intramuscularly with 3ml saline at 10.30h and
      0.1mg/kg PGF(2alpha) (Lutalyse, Upjohn) at 11.30h. Behaviour was scored for 1h
      after treatment with saline and 1h after treatment with PGF(2alpha) using
      one/zero sampling from video recordings. Nest building behaviour (rooting, pawing
      and gathering straw) was induced by PGF(2alpha) at all temperatures in both LW
      and LB breeds. There was a significant increase in rooting behaviours with
      decreasing temperature. No significant effects of temperature were found on the
      scores for gather or paw. The pigs spent more time lying down at the high
      compared to the low temperature after both saline and PGF(2alpha) treatment.
      Other behaviours unrelated to nest building but induced by PGF(2alpha), such as
      scratching, were unaffected by temperature. The results show that the nest
      building behaviour of non-pregnant pigs can be induced by exogenous PGF(2alpha)
      treatment, and that some, but not all, aspects of PGF(2alpha)-induced nest
      building (rooting but not pawing or gathering) are altered by environmental
      temperature.

PMID- 11248380
TI  - Use of perches and nestboxes by laying hens in relation to social status, based
      on examination of consistency of ranking orders and frequency of interaction.
AB  - Four groups of 15-19 adult ISA Brown hens were studied in pens to assess the
      relationship between social status and use of perches and nestboxes. This was to
      test the hypothesis that subordinate hens use these resources more by day, for
      avoiding dominants, but that dominants use perches more at night, for roosting.
      The experiment consisted of a 5-week pre-treatment period, when no perches were
      present, and a 4-week treatment period, when each group was tested with different
      perch treatments (No, Low, Medium, High). All groups were observed systematically
      in each week, when all interactions of three types (aggressive peck, non
      aggressive peck, approach/avoidance) in a group were recorded by noting the
      instigator and recipient (from numbered wing tags) onto a matrix. Proportions of
      time that each bird spent using perches and nestboxes, by day and at night, were
      also recorded. The results indicate that social status of individual laying hens
      is relatively stable across time and can be based reliably on counts of either
      aggressive pecks or approach/avoidances, but not non-aggressive pecks. Aggressive
      pecks were the most frequent type of interaction observed, and were reduced by
      the presence of perches. Use of nestboxes, but not perches, was greater at night
      than by day. There were weak tendencies for perches, and to a lesser extent
      nestboxes, to be used more by lower ranking birds by day, but not at night. There
      was some evidence of increased use of these resources by higher ranking birds at
      night. It is concluded that provision of perches reduces bird density on the
      floor (where nearly all interactions occurred), allows subordinates a means of
      avoiding dominants by day, reduces frequency of agonistic interactions, and
      should thus benefit laying hen welfare.

PMID- 11248381
TI  - The effects of operant control over food and light on the behaviour of domestic
      hens.
AB  - In intensive farming systems, the animals have little control over important
      elements in their environments. For instance, food of a pre-set type is delivered
      at set times, and the lighting schedule is controlled by the farmer. It has been
      suggested that low levels of environmental control over important events may
      reduce welfare by increasing passivity and stress. This study aimed to evaluate
      the effect of providing control over food and lighting additional to a restricted
      regime on the behaviour of small groups of laying hens (Gallus gallus
      domesticus). Twelve pens, each containing five birds, were paired to give six
      controlling and six non-controlling pens. These pairs of pens were yoked, such
      that birds in the controlling pens were able to make an operant response to gain
      access to extra food and light, whilst the yoked pens also received these
      outcomes but were unable to control their occurrence. The birds were kept
      continuously in the experimental conditions for 9 weeks. Records were made of
      general behaviour and activity, aggression and plumage damage scores, every 2
      weeks. Data on key-pecking and egg production were continuously recorded
      throughout the experiment. The controlling birds used the operant keys to open
      the feeder for an average of 92min and to turn on the light for 46min per pen per
      day. The high number of key-pecks indicates that the birds were motivated to make
      use of the keys to control access to additional food and light. The non
      controlling treatment pens showed significantly higher levels of preening and
      resting. Contrary to previous studies the use of operant feeders in this
      experiment did not induce a high level of feather pecking or aggressive
      interactions, as there was no significant difference between treatments. During
      the experiment the non-controlling hens laid significantly more eggs than the
      controlling hens. The results suggest that lack of control over these particular
      environmental events induced mild stress in the non-controlling pens of birds,
      and that further investigations into the effect of lack of control on welfare
      would be warranted.

PMID- 11248382
TI  - A note on using a laser-based technique for recording of behaviour and location
      of free-ranging animals.
AB  - We developed a precise, remote (up to 300m) observation system to record animal
      location and behaviour that requires no animal handling or disruption of the
      normal environment. Our system, combining a survey laser and a laptop, also
      allows recording of observed animal behaviour from seconds to hours, with
      accuracy of 1m or better. Up to one individual per second can be located, which
      supports data collection of large numbers of animals not possible with other
      methods. The laser system was used to track a halter-broken heifer led in an arc
      beginning and ending about 50m from the laser with a maximum distance of about
      150m. We recorded the location of the heifer at 35 points along the arc using the
      laser, a global positioning system (GPS), and a nylon tape. There was an average
      linear difference of 1.16m (S.D. 0.63) between the laser data and the GPS data.
      The laser was potentially more accurate than GPS for this application because the
      laser averaged only 0.21m (S.D. 0.24) linear difference from the tape. Tests of
      the laser to relocate points in the field to within 0.20m and 0.1 degrees,
      averaged 0.42m (S.D. 0.29) from the original points. Our technique allows precise
      location of behaviour and navigation to grazed sites, potentially revealing how
      animals interact with the resources they exploit and showing the effect of
      landscape spatial heterogeneity on foraging and habitat use patterns.

PMID- 11248383
TI  - Behavioural responses of South American fur seals to approach by tourists - a
      brief report.
AB  - I studied the responses (retreats, threats, attacks or leaving the rookery) of
      South American fur seals Arctocephalus australis to tourist approaches at a non
      reproductive, continental colony of located in Cabo Polonio, Uruguay (34 degrees
      24'S, 53 degrees 46'W). Fur seals tolerated relatively close distances to humans,
      but a strong response of the animals was elicited when tourists crossed a
      threshold of 10m. The attitude of the tourist was also important. Calm people
      were able to approach the colony without almost any disturbance. These results
      suggested that, with a minimal control of visitor's behaviour, the impact of
      tourism on this colony would be low.

PMID- 11248384
TI  - Ecological and molecular investigations of cyanotoxin production.

PMID- 11248385
TI  - Feasibility of using GFP-expressing Escherichia coli, coupled with fluorimetry,
      to determine protozoan ingestion rates.
AB  - The feasibility of using a live Escherichia coli population, which had been
      engineered to express the green fluorescent protein (GFP), coupled with
      fluorimetry, was tested as a means for determining protozoan ingestion rates. Its
      potential use was based on evidence that once cells are acidified, e.g. in a food
      vacuole, the fluorescence is lost. Of the 29 protozoa tested, over 85% ingested
      the GFP-expressing E. coli and a detailed experiment with the ciliate Tetrahymena
      pyriformis was carried out, principally to assess the performance of the live
      bacterium against two commonly used surrogate prey, i.e. fluorescently labelled
      bacteria (FLB) and fluorescently labelled microspheres (FLMs). A decrease in GFP
      expressing E. coli fluorescence and, hence, concentration, was recorded by
      fluorimetry and epifluorescence microscopy, with calculated ingestion rates being
      equivalent. A higher ingestion rate was determined by counting the number of
      fluorescent E. coli within the ciliate over 120 s, but this was equivalent to
      that obtained for the stained E. coli using the same direct method of analysis.
      However, the ciliate was shown to process the stained and unstained E. coli cells
      differently, with only the latter resulting in an increase in ciliate abundance.

PMID- 11248386
TI  - Bacterial and archaeal 16S rDNA and 16S rRNA dynamics during an acetate crisis in
      an anaerobic digestor ecosystem.
AB  - The dynamics of bacterial and archaeal populations of a laboratory-scale
      anaerobic digestor were investigated during a crisis period of the process
      reflected by an accumulation of acetate. A culture-independent approach based on
      single strand conformation polymorphism (SSCP) analysis of total 16S rDNA and 16S
      rRNA amplification products was used. A spirochete and a Synergistes sp. showed
      high and changing activity levels during the study. A Clostridium sp. showed a
      transient increase in presence and activity concomitant with the highest acetate
      concentrations. A major shift in the most active archaeal populations from
      hydrogenotrophic to acetoclastic methanogens preceded the recovery of the
      reactor.

PMID- 11248387
TI  - Molecular phylogenetic profiling of prokaryotic communities in guts of termites
      with different feeding habits.
AB  - Termites are an important group of terrestrial insects that harbor an abundant
      gut microbiota, many of which contribute to digestion, termite nutrition and gas
      (CH(4), CO(2) and H(2)) emission. With 2200 described species, termites also
      provide a good model to study relationships between host diet and gut microbial
      community structure and function. We examined the relationship between diet and
      gut prokaryotic community profiles in 24 taxonomically and nutritionally diverse
      species of termites by using nucleic acid probes targeting 16S-like ribosomal
      RNAs. The relative abundance of domain-specific 16S-like rRNAs recovered from gut
      extracts varied considerably (ranges: Archaea (0-3%); Bacteria (15-118%)).
      Although Bacteria were always detectable and the most abundant, differences in
      domain-level profiles were correlated with termite diet, as evidenced by higher
      relative abundances of Archaea in guts of soil-feeding termites, compared to
      those of wood-feeding species in the same family. The oligonucleotide probes also
      readily distinguished gut communities of wood-feeding taxa in the family
      Termitidae (higher termites) from those of other wood-feeding termite families
      (lower termites). The relative abundances of 16S-like archaeal rRNA in guts were
      positively correlated with rates of methane emission by live termites, and were
      consistent with previous work linking high relative rates of methanogenesis with
      the soil (humus)-feeding habit. Probes for methanogenic Archaea detected members
      of only two families (Methanobacteriaceae and Methanosarcinaceae) in termite
      guts, and these typically accounted for 60% of the all archaeal probe signal. In
      four species of termites, Methanosarcinaceae were dominant, a novel observation
      for animal gut microbial communities, but no clear relationship was apparent
      between methanogen family profiles and termite diet or taxonomy.

PMID- 11248388
TI  - Impact of cultivation on characterisation of species composition of soil
      bacterial communities.
AB  - The species composition of culturable bacteria in Scottish grassland soils was
      investigated using a combination of Biolog and 16S rDNA analysis for
      characterisation of isolates. The inclusion of a molecular approach allowed
      direct comparison of sequences from culturable bacteria with sequences obtained
      during analysis of DNA extracted directly from the same soil samples. Bacterial
      strains were isolated on Pseudomonas isolation agar (PIA), a selective medium,
      and on tryptone soya agar (TSA), a general laboratory medium. In total, 12 and 21
      morphologically different bacterial cultures were isolated on PIA and TSA,
      respectively. Biolog and sequencing placed PIA isolates in the same taxonomic
      groups, the majority of cultures belonging to the Pseudomonas (sensu stricto)
      group. However, analysis of 16S rDNA sequences proved more efficient than Biolog
      for characterising TSA isolates due to limitations of the Microlog database for
      identifying environmental bacteria. In general, 16S rDNA sequences from TSA
      isolates showed high similarities to cultured species represented in sequence
      databases, although TSA-8 showed only 92.5% similarity to the nearest relative,
      Bacillus insolitus. In general, there was very little overlap between the
      culturable and uncultured bacterial communities, although two sequences, PIA-2
      and TSA-13, showed >99% similarity to soil clones. A cloning step was included
      prior to sequence analysis of two isolates, TSA-5 and TSA-14, and analysis of
      several clones confirmed that these cultures comprised at least four and three
      sequence types, respectively. All isolate clones were most closely related to
      uncultured bacteria, with clone TSA-5.1 showing 99.8% similarity to a sequence
      amplified directly from the same soil sample. Interestingly, one clone, TSA-5.4,
      clustered within a novel group comprising only uncultured sequences. This group,
      which is associated with the novel, deep-branching Acidobacterium capsulatum
      lineage, also included clones isolated during direct analysis of the same soil
      and from a wide range of other sample types studied elsewhere. The study
      demonstrates the value of fine-scale molecular analysis for identification of
      laboratory isolates and indicates the culturability of approximately 1% of the
      total population but under a restricted range of media and cultivation
      conditions.

PMID- 11248389
TI  - The physiological and genetic diversity of bovine Streptococcus bovis strains(1).
AB  - Laboratory Streptococcus bovis strains and isolates obtained from a steer fed
      increasing amounts of grain had similar growth characteristics, but they differed
      in their sensitivity to 2-deoxyglucose (2DG), a non-metabolizable glucose analog.
      The addition of 2DG decreased both growth rate (0.92+/-0.34 h(-1)) and growth
      yield (ranging from 25 to 63%), but these differences could not be correlated
      with diet. However, isolates from a steer fed a 90% grain diet were more prone to
      2DG-dependent lysis than those from a hay diet (P<0.001). All S. bovis laboratory
      strains and isolates had an identical restriction fragment length polymorphism
      pattern, when their 16S rDNA was digested with HaeIII and HhaI. However, when
      genomic BOX elements were amplified, 5-12 bands were observed, and the S. bovis
      isolates and laboratory strains could be grouped into 13 different BOX types.
      Strains 26 and 581AXY2 had the same BOX type, but the remaining laboratory
      strains did not form closely related clusters. Strains JB1 and K27FF4 were most
      closely related to each other. Most of the fresh isolates (24 out of 30) could be
      grouped into a single cluster (>90% Dice similarity). This cluster contained
      isolates from all three diets, but it did not have any of the laboratory strains.
      The majority (90%) of the isolates obtained from the hay-fed steer exhibited the
      same BOX type. Because more BOX types were observed if grain was added to the
      diet, it appears that ruminal S. bovis diversity may be a diet-dependent
      phenomenon.

PMID- 11248390
TI  - The role of motility in the in vitro attachment of Pseudomonas putida PaW8 to
      wheat roots.
AB  - The attachment of motile and non-motile strains of Pseudomonas putida PaW8 to
      sterile wheat roots was assessed in both non-competitive and intra-specific
      competitive assays. The motile strain showed significantly greater attachment to
      wheat roots than non-motile strains in phosphate buffer. Overall, the motile
      strain attached better than the non-motile strain at 10(6), 10(7) and 10(8) cfu
      ml(-1) in competitive assays and at 10(6) and 10(7) cfu ml(-1) in non-competitive
      assays. When attachment was studied in Luria broth no significant difference
      between motile and non-motile strains was detected. P. putida PaW8 cells marked
      with the luxAB genes were used to compare direct detection of attached cells by
      luminometry with indirect detection by dilution plate counts following extraction
      from root material. Although direct detection permitted a rapid assessment (60 s)
      of attachment to surfaces, dilution plate counts provided a more sensitive method
      for quantification of bacteria. The detection limits were approximately 10 cfu
      root(-1) using dilution plate counts compared with 1000 cfu root(-1) using
      luminometry. All results highlighted the importance of motility for the
      attachment of P. putida to plant roots in simple model systems. To take this work
      further, studies to assess the role of motility using complex non-sterile systems
      are needed.

PMID- 11248391
TI  - Inhibition of algal spore germination by the marine bacterium Pseudoalteromonas
      tunicata.
AB  - A collection of 56 bacteria isolated from different surfaces in the marine
      environment were assayed for their effects on the germination of spores from the
      common green alga Ulva lactuca. Thirteen bacterial isolates were shown to inhibit
      spore germination. Of these bacteria, Pseudoalteromonas tunicata displayed the
      most pronounced effects against algal spores. Further characterisation of the
      anti-algal activity of P. tunicata was performed and it was found that this
      bacterium produces an extracellular component with specific activity toward algal
      spores that is heat-sensitive, polar and between 3 and 10 kDa in size. This
      biologically active compound was also found to prevent the germination of spores
      from the red alga Polysiphonia sp. and, given the widespread occurrence of P.
      tunicata in a range of marine habitats, this may suggest that it is effective
      against a variety of marine algae.

PMID- 11248392
TI  - Enhanced degradation of phenoxyacetic acid in soil by horizontal transfer of the
      tfdA gene encoding a 2,4-dichlorophenoxyacetic acid dioxygenase.
AB  - Few studies have investigated the possible impact of in situ gene transfer on the
      degradation of xenobiotic compounds in natural environments. In this work we
      showed that horizontal transfer of the tfdA gene, carried on plasmid pRO103, to
      phenol degrading recipient strains significantly increased the degradation rate
      of phenoxyacetic acid in sterile and non-sterile soil microcosms. The tfdA gene
      encodes a 2,4-dichlorophenoxyacetic acid/2-oxoglutarate dioxygenase and by
      complementation with the phenol degradation pathway an expanded catabolic
      substrate range, now including phenoxyacetic acid, is evolved. Presence of
      selective pressure had a positive effect on the emergence of transconjugants.
      However, even in the absence of phenoxyacetic acid transconjugant populations
      were detected and were kept at a constant level throughout the experimental
      period. The residuesphere (interface between decaying plant material and soil
      matrix) of dry leaves of barley was shown to be a hot-spot for gene transfer and
      presence of barley straw increased the conjugation frequencies in soil microcosms
      to the same extent as presence of organic nutrients. The results of this study
      indicate that dissemination of catabolic plasmids is a possible mechanism of
      genetic adaptation to degradation of xenobiotic compounds in natural
      environments, and that complementation of catabolic pathways possibly plays an
      important role in the evolution of new degradative capabilities. The application
      of horizontal gene transfer as a possible tool in bioremediation of contaminated
      sites is discussed.

PMID- 11248393
TI  - Phylogenetic analysis of the succession of bacterial communities in the Great
      South Bay (Long Island).
AB  - Bacterial community composition and succession were examined over the course of
      the summer season in the Great South Bay, Long Island, NY, USA, using a 16S rDNA
      clone library approach. There was a progression of changes in dominant species in
      the libraries during the summer of 1997. The July library had several groups
      dominant, the SAR407 relatives of the alpha-Proteobacteria (24%) and the SAR86
      (18%), sulfur-oxidizing symbiont relatives (8%) of the gamma-Proteobacteria, and
      unidentified Cytophaga-Flexibacter representatives (22%). In August, the
      Cytophaga-Flexibacter (Gelidibacter sp. and unidentified Cytophaga-Flexibacter
      representative) and Cyanobacteria (Synechococcus sp.) increased to 28% and 14%,
      respectively. High GC Gram-positives appeared at 18%, and beta-Proteobacteria
      (Ralstonia sp.) at 10%. By September these groups had either declined or were
      absent, while the SAR86 cluster, Pseudoalteromonas and Alteromonas of the gamma
      Proteobacteria were dominant in the community (61%). The dominance of open ocean
      bacteria along with the presence of Aureococcus anophagefferens (Pelagophyceae)
      in July suggests possible open ocean coupling to bloom events. Many clones in
      this study were related to previously described clones from a wide distribution
      of marine environments, substantiating the cosmopolitan nature of pelagic
      bacteria. Only one isolated bacterium was closely related to 16S rDNA found in
      the August library.

PMID- 11248394
TI  - Bacterial populations and processes involved in acetate and propionate
      consumption in anoxic brackish sediment.
AB  - Bacterial populations and pathways involved in acetate and propionate consumption
      were studied in anoxic brackish sediment from the Grosser Jasmunder Bodden,
      German Baltic Sea. Uptake of acetate and propionate from the porewater was
      studied using stable carbon isotope-labeled compounds. Labeled acetate was not
      produced as an intermediate during propionate uptake experiments, and propionate
      consumption was not affected by the addition of acetate. In parallel,
      incorporation of labeled acetate and propionate into phospholipid-derived fatty
      acids (PLFA) was studied to indicate bacterial populations involved in the
      consumption of these substrates. The (13)C-acetate label was mainly recovered in
      even-numbered PLFA (16:1omega7c, 16:0 and 18:1omega7c). In contrast, primarily
      odd-numbered PLFA (a15:0, 15:0, 17:1omega6 and 17:0) and the even-numbered i16:0
      were labeled after incubation with (13)C-propionate. Although single PLFA labeled
      with propionate are commonly found in sulfate reducers, the complete PLFA
      labeling pattern does not resemble any of the know strains. However, the acetate
      labeling pattern is similar to Desulfotomaculum acetoxidans and Desulfofrigus
      spp., two acetate-consuming, sulfate reducers. In conclusion, our data suggest
      that acetate and propionate were predominantly consumed by different, specialized
      groups of sulfate-reducing bacteria.

PMID- 11248395
TI  - Environmental factors influencing the distribution of rRNA from Verrucomicrobia
      in soil.
AB  - The Verrucomicrobia constitute a newly discovered division of the Bacteria
      identified as a numerically abundant component of soil microbial communities in
      numerous sites around the world. The relative abundance of rRNA from
      Verrucomicrobia was investigated in the soil to examine the influence of specific
      environmental factors on the distribution of Verrucomicrobia and to better
      understand the distribution of this group in terrestrial ecosystems. The
      abundance of the verrucomicrobial rRNA was determined by using a novel
      oligonucleotide probe that is specific for verrucomicrobial 16S rRNA. The
      abundance of verrucomicrobial 16S rRNA in soil microbial communities was
      determined in relation to plant community composition and soil management history
      over a period of 2 years. Additional samples were analyzed to determine if
      verrucomicrobial rRNA relative abundance changes in relation to either soil depth
      or soil moisture content. The Verrucomicrobia composed 1.9+/-0.2% of the
      microbial community rRNA present in the 85 soil samples examined. The
      distribution of verrucomicrobial rRNA in the soil reveals that Verrucomicrobia
      are significantly affected by environmental characteristics that change in
      relation to time, soil history, and soil depth, and reveals that a statistically
      significant amount of the variation in verrucomicrobial rRNA abundance can be
      explained by changes in soil moisture content.

PMID- 11248396
TI  - Amino acids and their transporters in the retina.
AB  - This review provides an overview of the distributions, properties and roles of
      amino acid transport systems in normal and pathological retinal tissues and
      discusses the roles of specific identified transporters in the mammalian retina.
      The retina is used in this context as a vehicle for describing neuronal and glial
      properties, which are in some, but not all cases comparable to those found
      elsewhere an the brain. Where significant departures are noted, these are
      discussed in the context of functional specialisations of the retina and its
      relationship to adjacent supporting tissues such as the retinal pigment
      epithelium. Specific examples are given where immunocytochemical labelling for
      amino acid transporters may yield inaccurate results, possibly because of
      activity-dependent conformation changes of epitopes in these proteins which
      render the epitopes more or less accessible to antibodies.

PMID- 11248397
TI  - Kainate-induced genes in the hippocampus: lessons from expression patterns.
AB  - Kainate, the analog of the excitatory amino acid L-glutamate, upon binding to non
      NMDA glutamate receptors, causes depolarization of neurons followed by severe
      status epilepticus, neurodegeneration, plasticity and gliosis. These events are
      best observed in hippocampus, the limbic structure implicated in learning and
      long-term memory formation. Neurons in all hippocampal structures undergo hyper
      activation, however, whereas the cells in the CA subfields degenerate within 2--3
      days following the application of kainate, the granule cells of the dentate gyrus
      are resistant to any form of neurodegeneration and even initiate new synaptic
      contacts. These physiological and histological changes are modulated by short
      term and long-term alterations in gene expression. Perhaps close examination of
      the changing spatio-temporal patterns of mRNAs of various genes may help in
      generating a clearer picture of the molecular events leading to complex cognitive
      functions.

PMID- 11248398
TI  - Molecular genetics of Rett syndrome.
AB  - Rett syndrome is a neurodevelopmental disorder affecting almost exclusively
      females. It affects approximately one in 15000 females and is characterized by a
      loss of purposeful hand use, autism, ataxia and seizure. The disorder is usually
      sporadic, but rare familial cases have also been reported. Recently it has been
      shown that familial cases are an X-linked dominant disorder and the disease locus
      maps to Xq28. A candidate gene called methyl-CpG-binding protein 2 was identified
      from the Xq28 region and was shown to contain mutations in about 77% of Rett
      syndrome patients. Since the encoded protein was previously shown to be a global
      transcriptional repressor, undesired expression of yet unidentified genes that
      are normally repressed is considered to be pathogenic in Rett syndrome.

PMID- 11248399
TI  - Blockade of AMPA/kainate receptors can either decrease or increase the survival
      of cultured neocortical cells depending on the stage of maturation.
AB  - Neurotoxicity has often been associated with glutamate receptor stimulation and
      neuroprotection with glutamate receptor blockade. However, the relationship may
      be much more complex. We dissociated cells from the rat neocortical anlage at an
      early stage of prenatal development (embryonic day 14). The cells were exposed in
      vitro to agonists and antagonists of alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionate (AMPA)/kainate and N-methyl-D-aspartate (NMDA) receptors and the
      effects on differentiation and survival have been quantitatively and
      qualitatively evaluated. NMDA and the non-competitive antagonist (5R,10S)-(+)-5
      methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine hydrogen maleate (MK
      801) had the expected effects (the agonist decreasing and the antagonist
      increasing neuronal survival) when applied at a relatively advanced stage of in
      vitro maturation, but no significant effect in either direction at earlier
      stages. Kainate also had an effect on cell survival only at an advanced stage
      (where it decreased the number of cells). However, this cannot be attributed to
      the absence of functional AMPA/kainate receptors at earlier stages, since: (1)
      cells could be loaded with cobalt; and (2) early application of kainate
      dramatically reduced the number of cobalt-positive cells. Furthermore, exposure
      at early stages to 6,7-dinitroquinoxaline-2,3-dione (DNQX), or GYKI 53655,
      (competitive and non-competitive AMPA receptor antagonists, respectively)
      strongly reduced cell survival. The effects were concentration- and time
      dependent with a complex time--curve. The decrease in cell number was maximal
      after antagonist application from 2 to 5 days in vitro. The effects of DNQX could
      be cancelled by co-application of kainate. When exposed to an antagonist at later
      stages of development, the number of surviving cells gradually approached control
      values and finally became significantly higher. Our results suggest that cells of
      the developing neocortex (and perhaps newly generated cells in the adult brain)
      require at different stages of their development, an appropriate level of
      AMPA/kainate receptor activation.

PMID- 11248400
TI  - Diet-induced ketosis increases monocarboxylate transporter (MCT1) levels in rat
      brain.
AB  - Monocarboxylate transporter (MCT1) levels in brains of adult Long-Evans rats on a
      high-fat (ketogenic) diet were investigated using light and electron microscopic
      immunocytochemical methods. Rats given the ketogenic diet (91% fat and 9%
      protein) for up to 6 weeks had increased levels of the monocarboxylate
      transporter MCT1 (and of the glucose transporter GLUT1) in brain endothelial
      cells and neuropil compared to rats on a standard diet. In ketonemic rats,
      electron microscopic immunogold methods revealed an 8-fold greater MCT1 labeling
      in the brain endothelial cells at 4 weeks. Abluminal endothelial membranes were
      twice as heavily labeled as luminal membranes. In controls, luminal and abluminal
      labeling was not significantly different. The endothelial cytoplasmic compartment
      was sparsely labeled (<8% of total endothelial labeling) in all brains. Neuropil
      MCT1 staining was more intense throughout the brain in ketonemic rats, especially
      in neuropil of the molecular layer of the cerebellum, as revealed by avidin
      biotin immunocytochemistry. This study demonstrates that adult rats retain the
      capacity to upregulate brain MCT1 levels. Furthermore, their brains react to a
      diet that increases monocarboxylate levels in the blood by enhancing their
      capability to take up both monocarboxylates (MCT1 upregulation) and glucose
      (GLUT1 upregulation). This may have important implications for delivery of fuel
      to the brain under stressful and pathological conditions, such as epilepsy and
      GLUT1 deficiency syndrome.

PMID- 11248401
TI  - Reduction of large neutral amino acid levels in plasma and brain of
      hyperleucinemic rats.
AB  - Neurological dysfunction is common in patients with maple syrup urine disease
      (MSUD). However, the mechanisms underlying the neuropathology of this disorder
      are poorly known. In the present study we investigated the effect of acute
      hyperleucinemia on plasma and brain concentrations of amino acids. Fifteen-day
      old rats were injected subcutaneously with 6 micromol L-leucine per gram body
      weight. Controls received saline in the same volumes. The animals were sacrificed
      30--120 min after injection, blood was collected and their brain rapidly removed
      and homogenized. The amino acid concentrations were determined by HPLC using
      orthophtaldialdehyde for derivatization and fluorescence for detection. The
      results showed significant reductions of the large neutral amino acids (LNAA) L
      phenylalanine, L-tyrosine, L-isoleucine, L-valine and L-methionine, as well as L
      alanine, L-serine and L-histidine in plasma and of L-phenylalanine, L-isoleucine,
      L-valine and L-methionine in brain, as compared to controls. In vitro experiments
      using brain slices to study the influence of leucine on amino acid transport and
      protein synthesis were also carried out. L-Leucine strongly inhibited [14C]-L
      phenylalanine transport into brain, as well as the incorporation of the [14C]
      amino acid mixture, [14C]-L-phenylalanine and [14C]-L-lysine into the brain
      proteins. Although additional studies are necessary to evaluate the importance of
      these effects for MSUD, considering previous findings of reduced levels of LNAA
      in plasma and CSF of MSUD patients during crises, it may be speculated that a
      decrease of essential amino acids in brain may lead to reduction of protein and
      neurotransmiter synthesis in this disorder.

PMID- 11248402
TI  - Expression of GluR6/7 subunits of kainate receptors in rat adenohypophysis.
AB  - We have previously demonstrated the presence of unidentified [3H]glutamate (Glu)
      binding sites with stereo-selectivity, high affinity and saturability in rat
      peripheral excitable tissues such as the pituitary (Yoneda, Y., Ogita, K., 1986a.
      [3H]Glutamate binding sites in the rat pituitary. Neurosci. Res. 3, 430--435) and
      adrenal (Yoneda, Y., Ogita, K., 1986b. Localization of [3H]glutamate binding
      sites in rat adrenal medulla. Brain Res. 383, 387--391, 1986). In this study,
      peripheral binding sites were further evaluated for the ionotropic Glu receptor
      subtype insensitive to N-methyl-D-aspartate by using reverse transcription
      polymerase chain reaction (RT-PCR) and Western blotting, in addition to receptor
      binding using radiolabeled ligands other than [3H]Glu. Binding of [3H]kainate
      (KA) and [3H]DL-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate was detected
      in membrane preparations obtained from the rat pituitary and adrenal irrespective
      of prior treatment with Triton X-100. An RT-PCR analysis revealed constitutive
      expression of mRNA for GluR1, GluR3, GluR5, KA1 and KA2 subunits in the rat
      adrenal and pituitary, as well as the brain and retina. The pituitary also
      expressed mRNA for GluR2, GluR4, GluR6 and GluR7 subunits in contrast to the
      adrenal. Under our experimental conditions employed, however, Western blotting
      assays failed to confirm the expression of receptor proteins for GluR1, GluR2/3
      and GluR4 subunits in the adrenal cortex, adrenal medulla, adenohypophysis and
      neurohypophysis. Immunoreactive GluR6/7 subunits were only detectable in the
      adenohypophysis, but not in the adrenal cortex, adrenal medulla and
      neurohypophysis. An intraperitoneal injection of KA doubled DNA binding activity
      of the nuclear transcription factor activator protein-1 in the rat pituitary,
      with concomitant more potent potentiation of that in the hippocampus. These
      results suggest that GluR6/7 subunits of KA receptors may be constitutively
      expressed with responsiveness to the systemic administration of an agonist at
      least in the rat adenohypophysis.

PMID- 11248403
TI  - Biologically active dihydropyrimidones of the Biginelli-type--a literature
      survey.
AB  - In 1893, the synthesis of functionalized 3,4-dihydropyrimidin-2(1H)-ones (DHPMs)
      via three-component condensation reaction of an aromatic aldehyde, urea and ethyl
      acetoacetate was reported for the first time by P. Biginelli. In the past
      decades, such Biginelli-type dihydropyrimidones have received a considerable
      amount of attention due to the interesting pharmacological properties associated
      with this heterocyclic scaffold. In this review, we highlight recent developments
      in this area, with a focus on the DHPMs recently developed as calcium channel
      modulators, alpha(1a) adrenoceptor-selective antagonists and compounds that
      target the mitotic machinery.

PMID- 11248404
TI  - Synthesis, structural characterization and antitumor activity of novel 2,4
      diamino-1,3,5-triazine derivatives.
AB  - The syntheses, structural elucidation based on NMR spectroscopy and X-ray
      analysis of 8 as well as antitumor activities of novel 2,4-diamino-1,3,5-triazine
      derivatives 5 and 7-22 are described. Screenings performed at NCI showed that
      most derivatives possessed a moderate to strong growth inhibition activity on
      various tumor panel cell lines between 0.148 and 56.2 microM concentrations. 2
      Amino-6-bromomethyl-4-(3,5,5-trimethyl-2-pyrazoline)-1,3,5-triazine 11 showed the
      most potent antitumor activity with the mean midpoint values of log(10) GI50,
      log(10) TGI50 and log(10) LC50 of all tests equal to -5.26, -4.81 and -4.37,
      respectively and therefore, it can be considered as a lead structure for further
      development of anticancer agents.

PMID- 11248405
TI  - Design, synthesis and binding properties of novel and selective 5-HT(3) and 5
      HT(4) receptor ligands.
AB  - This work reports the synthesis and the binding tests on the 5-HT(3) and 5-HT(4)
      receptors of new thienopyrimidopiperazine and
      piperazinylacylaminodimethylthiophene derivatives, in order to identify potent
      and selective ligands for each receptor. The compound with higher affinity and
      selectivity for the 5-HT(3) over the 5-HT(4) receptor was the 3-amino-2-(4-benzyl
      1-piperazinyl)-5,6-dimethyl-thieno[2,3-d]pyrimidin-4(3H)-one 28 (5-HT(3)
      K(i)=3.92 nM, 5-HT(4) not active), the compound with higher affinity and
      selectivity for the 5-HT(4) over the 5-HT(3) receptor was the 2-[4-[4-(2
      pyrimidinyl)-1-piperazinyl]butanoylamino]-4,5-dimethyl-3-thiophenecarboxylic acid
      ethyl ester 41 (5-HT(4) K(i)=81.3 nM, 5-HT(3) not active). Conformational
      analyses were carried out on the compounds of the
      piperazinylacylaminodimethylthiophene series (39-42) taking compound 41 as the
      template.

PMID- 11248406
TI  - Prediction of aqueous solubility for a diverse set of organic compounds based on
      atom-type electrotopological state indices.
AB  - We describe robust methods for estimating the aqueous solubility of a set of 734
      organic compounds from different structural classes based on multiple linear
      regression (MLR) and artificial neural networks (ANN) model. The structures were
      represented by atom-type electrotopological state (E-state) indices. The squared
      correlation coefficient and standard deviation for the MLR with 34 structural
      parameters were r(2) = 0.94 and s = 0.58 for the training set of 675 compounds.
      For the test set of 21 compounds, the equivalent statistics were r(2)(pred) =
      0.80 and s = 0.87, respectively. Neural networks gave a significant improvement
      using the same set of parameters, and the standard deviations were s = 0.52 for
      the training set and s = 0.75 for the test set when an artificial neural network
      with five neurons in the hidden layer was used. The results clearly show that
      accurate models can be rapidly calculated for the estimation of aqueous
      solubility for a large and diverse set of organic compounds using easily
      calculated structural parameters.

PMID- 11248407
TI  - Synthesis and cytotoxic effect of 1,3-dihydroxy-9,10-anthraquinone derivatives.
AB  - 1,3-Dihydroxy-9,10-anthraquinone (4) was reacted with epichlorohydrin or 1,omega
      dibromo-alkane to yield 1-hydroxy-3-(2,3-epoxypropoxy)-9,10-anthraquinone (5) and
      1-hydroxy-3-(3-chloro-2-hydroxypropoxy)-9,10-anthraquinone (6) or 1-hydroxy-3
      (omega-bromoalkoxy)-9,10-anthraquinone. Ring-opening of the epoxide (5) or 1
      hydroxy-3-(omega-bromoalkoxy)-9,10-anthraquinones with appropriate amines,
      afforded various 1-hydroxy-3-(3-alkylamino-2-hydroxypropoxy)-9,10-anthraquinones.
      The synthetic compounds were tested in vitro inhibition of human T-24, Hep 3B,
      Hep G2, SiHa, HT-3, PLC/PRF/5 and 212 cells. Almost all compounds showed
      significant inhibitory activity against several different cancer cell lines.
      Structure-activity analysis indicated epoxidation of the hydroxyanthraquinone
      increased cytotoxicity against tumour cells, but ring-opening of the epoxide
      group with amine did not enhance the cytotoxic activity. The phosphatidylserine
      (PS) externalization and DNA fragmentation in SiHa cells were significantly
      observed after 48 h incubation with selected compound 19. The results show that
      19 cause cell death by apoptosis.

PMID- 11248408
TI  - Comparative action of carbocyclic thromboxane A(2) stereoisomers on platelets.
AB  - Stereospecific requirements for the interaction of the thromboxane A(2)
      carbocyclic mimetic CTA(2) 1 with the human platelet PGH(2)/TXA(2) receptor have
      been explored. The two pairs of trans-1,2 and cis-3,4 side chain diastereoisomers
      were synthesised and evaluated for agonist and antagonist activity in human
      platelet rich plasma. Interestingly, the natural and unnatural trans
      diastereoisomers, both possessed potent aggregatory activity and equipotently
      inhibited platelet responses to subsequent addition of agonists, whereas, the
      respective unnatural cis isomers proved only weakly active or inert.

PMID- 11248409
TI  - Glycoglycerolipid analogues active as anti-tumor-promoters: the influence of the
      anomeric configuration.
AB  - The in vitro anti-tumor promoting effect of monohexanoates of 2-O-alpha-D-gluco-
      and galactopyranosyl-sn-glycerol on the 12-O-tetradecanoylphorbol-13-acetate
      (TPA) induced Epstein-Barr virus early antigen (EBV-EA) activation was evaluated
      and compared to the potencies of the corresponding beta-anomers. The results show
      that the inversion of the anomeric configuration from beta to alpha does not seem
      to significantly influence the activity, which is present, as for the beta
      anomers, even at 1x10 mol ratio without any cytotoxicity.

PMID- 11248410
TI  - Synthesis and in vitro antitumour activity evaluation of 1-aryl-1H,3H
      thiazolo[4,3-b]quinazolines.
AB  - A series of 1H,3H-thiazolo[4,3-b]quinazolines (2a-i) were synthesized and
      evaluated for their in vitro antitumour activity against ca. 60 human tumour cell
      lines. They exhibited moderate (2c, 2d, 2f and 2g) to strong (2a, 2b, 2e, 2h and
      2i) cell-growth inhibition at a concentration of 10(-4) M, but weak activity at
      lower concentrations. Only 1-(2,6-dichlorophenyl)-1H,3H-thiazolo[4,3
      b]quinazoline (2h) possesses a significant growth inhibitory activity on 22 cell
      lines at a concentration of 10(-5) M.

PMID- 11248411
TI  - Medicinal chemistry in the development of societies. Biodiversity and natural
      products.
AB  - This document has been elaborated by the IUPAC Medicinal Chemistry section and is
      backed by a large number of scientists, many of whom have had direct involvement
      and whose names appear at the end of the article. This work discusses the role
      that the discovery of new medicinal agents has in the development of societies as
      well as in the conservation of biodiversity in terms of work carried out on
      natural products. Also included are several recommendations for countries which
      are presently in search of their own scientific and technological development in
      medicinal agents. The IUPAC Medicinal Chemistry section would appreciate the
      collaboration of the scientific societies in every country to aid in the
      diffusion of this document.

PMID- 11248412
TI  - Rho signals to cell growth and apoptosis.
AB  - Ras and Rho GTPases are among the best studied signaling molecules in molecular
      biology. Essential cellular processes, such as cell growth, lipid metabolism,
      cytoarchitecture, membrane trafficking, transcriptional regulation, apoptosis,
      and response to genotoxic agents, are directly modulated by different members of
      this superfamily of proteins. Not until recently have we begun to understand the
      physiological implications of Ras and Rho GTPases, linking them to processes such
      as embryonic development, tissue remodeling, tumorigenesis and metastasis. In
      this sense, uncontrolled activation, due to overexpression of different members
      of the Rho family in a variety of tissues, leads to uncontrolled proliferation
      and invasiveness of human tumors. In this review, an attempt to briefly integrate
      recent findings in transcriptional regulation by Rho GTPases in the context of
      carcinogenesis and metastasis as well as apoptosis is made.

PMID- 11248414
TI  - Sialomucin production in aberrant crypt foci relates to degree of dysplasia and
      rate of cell proliferation.
AB  - Aberrant crypt foci (ACF) are putative early preneoplastic lesions of colon
      cancer. To date, many different ACF parameters have been measured as indicators
      of degree of colon cancer risk. It has been suggested that ACF producing
      sialomucins (SIM) may be more advanced types of ACF than those producing
      sulphomucins (SUM), but little data are available to support this. The objective
      of this experiment was to see if SIM ACF, as observed in whole mount colons, are
      different from other ACF and surrounding normal colonic crypts in terms of their
      rate of cell proliferation and degree of dysplasia. Results showed that all ACF
      had a higher rate of cell proliferation than normal crypts and that SIM ACF had
      higher cell proliferation in the top regions of the crypt, higher phih index of
      cell proliferation, higher degree of dysplasia, greater size and increased degree
      of luminal alterations than SUM ACF. We conclude that SIM ACF, as observed in
      whole mount colons, have more alterations and are more advanced towards
      tumorigenesis than SUM ACF and may be a better predictor of colon cancer risk
      than other measures of ACF.

PMID- 11248413
TI  - Dimethylarsinic acid induces 8-hydroxy-2'-deoxyguanosine formation in the kidney
      of NCI-Black-Reiter rats.
AB  - Dirnethylarsenic peroxyl radical [(CH(3))(2)AsOO] has been postulated to be
      responsible for DNA damage induced by dimethylarsinic acid (DMA). In an effort to
      elucidate the possible mechanism of tumor-inducing potential of DMA, an
      experiment was designed to investigate the formation of 8-hydroxy-2'
      deoxyguanosine (8-OHdG), a specific marker of oxidative base damage in the kidney
      tissues of NCI-Black Reiter (NBR) rats. Animals were divided into four groups and
      administered the vehicle - saline, 5, 10 and 20 mg/kg body weight respectively of
      DMA by gavage, once a day, 5 days a week, for a period of 4 weeks. DMA induced
      increase of 8-OHdG levels in the kidney of the rats treated, with the highest
      level at the dose of 10 mg/kg body weight. Analysis of the kidney for cell
      proliferation employing PCNA-positive index showed greater proliferation in the
      tissues of treated rats. However, DMA did not have any influence on apoptosis in
      this regimen. Histopathological examination of the kidney selections revealed the
      presence of vacuolated degeneration and dilation of the proximal tubule cells in
      two groups (10 and 20 mg/kg body weight). This study provides evidence to
      substantiate the role of DMA in inducing oxidative DNA damage in the kidney.

PMID- 11248415
TI  - Whole almonds and almond fractions reduce aberrant crypt foci in a rat model of
      colon carcinogenesis.
AB  - Almonds and other nuts appear to confer health benefits despite their high fat
      content. To assess the effect of almonds on colon cancer, whole almond-, almond
      meal- or almond oil-containing diet effects on aberrant crypt foci (ACF) in
      azoxymethane-treated F344 male rats were investigated. Six-week-old male F344
      rats were fed the various almond and control diets and given subcutaneous
      injections of azoxymethane (15 mg/kg body weight) twice 1 week apart. After 26
      weeks animals were injected with bromodeoxyuridine 1 h prior to sacrifice, after
      which colons were evaluated for ACF and cell turnover (labeling index, LI). Whole
      almond ACF and LI were both significantly lower than wheat bran and cellulose
      diet groups (-30 and -40%, respectively), while almond meal and almond oil ACF
      and almond meal LI declines were only significant vs. cellulose (P<0.05). These
      results suggest that almond consumption may reduce colon cancer risk and does so
      via at least one almond lipid-associated component.

PMID- 11248416
TI  - Inhibitory effect of berberine on the mediastinal lymph node metastasis produced
      by orthotopic implantation of Lewis lung carcinoma.
AB  - We examined the effect of berberine, a major component with anti-fungal
      properties contained in Coptidis Rhizoma and Phellodendri Cortex, on the lymph
      node metastasis of murine lung cancer. Oral administration of berberine for 14
      days significantly inhibited the spontaneous mediastinal lymph node metastasis
      produced by orthotopic implantation of Lewis lung carcinoma (LLC) into the lung
      parenchyma in a dose-dependent manner, but did not affect the tumor growth at the
      implantation site of the lung. Combined treatment with berberine and an anti
      cancer drug, CPT-11, resulted in a marked inhibition of tumor growth at the
      implantation site and of lymphatic metastasis, as compared with either treatment
      alone. Anti-activator protein-1 (anti-AP-1) transcriptional activity of non
      cytotoxic concentrations of berberine caused the inhibition of the invasiveness
      of LLC cells through the repression of expression of urokinase-type plasminogen
      activator (u-PA).

PMID- 11248417
TI  - In vitro and in vivo suppression of growth of hepatocellular carcinoma cells by
      albendazole.
AB  - Tubulin protein is a major target of drug molecules, and consequently, tubulin
      inhibitors have attracted great attention as antimitotic antitumor agents for
      chemotherapeutic use. It has been shown that, the benzimidazole carbamate group
      of antiparasitics including albendazole act by inhibiting tubulin polymerization.
      In this study, albendazole was tested in culture against a range of human, rat
      and mice hepatocellular carcinoma (HCC) cells and in vivo against human SKHEP-1
      tumor growth in nude mice. Albendazole induced a dose-dependent inhibition of
      [(3)H]thymidine incorporation in all cell lines examined and a dramatic decline
      in cell numbers in SKHEP-1 cells. The inhibitory effect of albendazole was
      evident at the 100 nM concentration and at 1000 nM, proliferation in all cell
      lines examined was inhibited by more than 80%, while, proliferation of HepG2,
      Hep3B and SKHEP-1 were suppressed by more than 90%, compared to control. Cell
      cycle analysis revealed that, depending on the dose employed, albendazole can
      arrest SKHEP-1 cells at both G0-G1 (250 nM) and G2-M (1000 nM) phases of the
      cycle. Albendazole treatment (300 mg/kg per day oral for 20 days) of nude mice
      inoculated subcutaneously with SKHEP-1, led to profound suppression of tumor
      growth. Immunohistochemical analysis of these tumors revealed that compared to
      control, those treated with albendazole have lower growth fractions. These
      findings demonstrate that albendazole strongly suppresses both in vitro and in
      vivo proliferation of HCC cells.

PMID- 11248418
TI  - Phthalocyanine 4 photodynamic therapy-induced apoptosis of mouse L5178Y-R cells
      results from a delayed but extensive release of cytochrome c from mitochondria.
AB  - Photodynamic therapy (PDT) activates the mitochondrial pathway of apoptosis, for
      which the release of cytochrome c into the cytosol is considered critical. To
      further elucidate the role of cytochrome c release in PDT-induced apoptosis, we
      monitored cytochrome c localization immunocytochemically and related it to
      nuclear apoptosis of the same cells. When mouse L5178Y-R cells were treated with
      300 nM phthalocyanine (Pc) 4 and 0-75 mJ/cm(2) red light, cytochrome c release
      had a dose response similar to that of clonogenic cell killing, with nearly
      identical threshold doses. Within individual cells, the release of cytochrome c
      appeared to be an all-or-none phenomenon. Moreover, it was tightly associated
      with activation of a caspase-3-like protease and changes in nuclear morphology.
      Thus, in response to Pc 4-PDT, the release of cytochrome c from mitochondria is a
      key determinant of apoptotic cell death.

PMID- 11248419
TI  - Polymorphisms in codon 31 of p21 and cervical cancer susceptibility in Korean
      women.
AB  - The aim of this study was to determine whether the codon 31 genotype of p21 might
      be associated with an increased risk of cervical cancer development in Korean
      women. We used tissue derived from patients with invasive cervical cancer (ICC)
      (n=111, composed of two histologic groups: squamous cell carcinoma (n=67) and
      adenocarcinoma (n=44)), cervical intraepithelial neoplasia (CIN) III (n=101), and
      non-cancer controls (NCC, n=98). For the determination of p21 polymorphism,
      genomic DNA was examined by polymerase chain reaction-restriction fragment length
      polymorphism assay using BsmAI. We compared the distribution of the p21 genotype
      in ICC, CIN III, and control and also analyzed the association of this
      polymorphism with the risk of development of cervical cancer, especially in
      patients with high-risk human papillomavirus (HPV) (16 or 18)-positive cervical
      cancer. A significant increase of Ser/Ser genotype frequency was found in
      adenocarcinoma patients with high-risk HPV (16 or 18) compared with the NCC group
      (P=0.009). The odds ratio was 3.59 (95% CI 1.55-8.31) when comparing
      adenocarcinoma patients associated with high-risk HPV with NCC. We found that the
      codon 31 Ser/Ser homozygote of the p21 gene could be a risk factor for the
      development of cervical adenocarcinoma associated with high-risk HPV.

PMID- 11248420
TI  - Down-regulation of matrix Gla protein messenger RNA in human colorectal
      adenocarcinomas.
AB  - Matrix Gla protein (MGP) is a vitamin K-dependent extracellular matrix protein
      commonly found in a variety of tissues. In this study, we describe the potential
      use of MGP gene expression as the tumor marker of colorectal cancer. A decrease
      in expression of the MGP gene was also discovered in colorectal cancer using
      differential screening of cDNA libraries. The MGP expression in 80 human
      colorectal adenocarcinomas was quantified by a Northern blot analysis to better
      define the expression pattern of MGP in colorectal cancer. The expression of MGP
      mRNA was reduced in 63 of 80 (79%) colorectal adenocarcinomas (P<0.001) as
      compared to the mRNA in adjacent normal tissue, implying that a decrease in MGP
      expression is associated with colorectal cancer development. The proportion of
      tumors with downregulated expression of MGP was lower in Duke's A/B than Duke's
      C/D (34 of 47 versus 26 of 33, respectively) tumors and was lower in moderate
      differentiation than poor differentiation (44 of 64 versus 16 of 16,
      respectively). However, chi(2) analysis does not reveal any correlation between a
      loss of MGP expression and tumor progression or differentiation state. In
      conclusion, the downregulation of MGP mRNA generally occurs in colorectal
      adenocarcinomas. Although the role of MGP in cancer development is unknown, the
      reduced expression of MGP may be used to distinguish the normal colorectal cells
      from malignant cells.

PMID- 11248421
TI  - The novel ependymin related gene UCC1 is highly expressed in colorectal tumor
      cells.
AB  - Normal cells differ from malignant tumor cells in the transcription levels of
      many different genes. Two colorectal tumor cell lines were compared with a normal
      colorectal cell line by differential display reverse transcription PCR to screen
      for tumor cell specific differentially transcribed genes. By this strategy the
      upregulation of a novel gene was detected designated as 'upregulated in
      colorectal cancer gene-1' (UCC1). The UCC1 gene transcript level is increased in
      cultured tumor cells and in two out of three analyzed colorectal tumor tissue
      specimens compared to normal cultured cells and to corresponding normal tissue
      samples. Remarkably, the UCC1 protein shows significant sequence similarity to
      the highly divergent piscine glycoproteins termed ependymins which are
      synthesized by leptomeningeal fibroblasts and secreted into the cerebrospinal
      fluid.

PMID- 11248423
TI  - Germline BRCA1 mutations in Iranian women with breast cancer.
AB  - BRCA1 is known as a familial early onset breast cancer gene located in the long
      arm of chromosome 17. Alterations in this gene have been reported in different
      populations, some of which are population-specific mutations showing a founder
      effect. In this study, which is the first report on the genetic testing of
      Iranian women, exon-2 of the BRCA1 gene was sequenced in 80 Iranian breast cancer
      patients and none of the patients showed the 185del AG mutation or any changes in
      the sequences of this exon. Among this population, 22 patients having one or more
      of any kind of tumor in their first-degree relatives were selected and their
      entire BRCA1 gene coding region was sequenced by direct PCR-sequencing. A novel
      point mutation in exon-16, with unknown significance, was observed among the
      breast cancer patients and control subjects. This A/G mutation caused the
      substitution of Glutamine 1612 with Glycine, with an allele frequency of 38.6 and
      52.8% in patients and controls, respectively. In addition, a point mutation in
      exon-15 and eight other polymorphic alterations were detected which have been
      reported previously. Three of these polymorphic sites were placed in the intronic
      part of the gene. To understand the significance of the contribution of the BRCA1
      gene in the breast cancer among Iranian, further investigations are needed.

PMID- 11248422
TI  - Overexpression of protein kinase A - RIalpha reduces lipofection efficiency of
      cisplatin-resistant human tumor cells.
AB  - Cisplatin-resistant variant A2780CP/vector cells were 4.0-5.3-fold more
      transfectable and 7.6-fold more resistant to cisplatin than their parent
      cisplatin-sensitive human ovarian carcinoma A2780/vector cells. Overexpression of
      cAMP-dependent protein kinase Type I regulatory alpha subunit (PKA-RIalpha) gene
      in A2780CP cells significantly reduced (maximum 47.0%) the transfection activity,
      with a slight reduction (maximum 27.3%) of cisplatin resistance, of A2780CP
      cells. However, RIalpha-overexpressing A2780CP (A2780CP/RIalpha) cells were still
      2.5-to 3.0-fold more transfectable and 5.5-fold more resistant to cisplatin than
      A2780 cells. This results suggest that gene transfer efficiency is associated
      with cisplatin resistance, in part, through the PKA-mediated cAMP signal
      transduction pathway.

PMID- 11248424
TI  - Suppression of CYP1A1 expression by 4-nonylphenol in murine Hepa-1c1c7 cells.
AB  - This study investigated the effects that 4-nonylphenol (NP) has on CYP1A1
      expression in Hepa-1c1c7 cell cultures. NP alone did not affect CYP1A1-specific 7
      ethoxyresorufin-O-deethylase (EROD) activity. In contrast, the 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD)-inducible EROD activities were markedly
      reduced upon concomitant treatment with TCDD and NP in a dose-dependent manner.
      Treatment with tamoxifen, an anti-estrogen that acts through the estrogen
      receptor, did not affect the suppressive effects that NP has on TCDD-inducible
      EROD activity. The TCDD-inducible CYP1A1 mRNA levels were markedly suppressed
      upon concomitant treatment with TCDD and NP that is consistent with their effects
      on EROD activity. A transient transfection assay using dioxin-response element
      (DRE)-linked luciferase and an electrophoretic mobility shift assay revealed that
      NP reduced the transformation of the aryl hydrocarbon (Ah) receptor to a form
      capable of binding specifically to the DRE sequence of the CYP1A1 gene promoter.
      These results suggest that the down-regulation of CYP1A1 gene expression by NP in
      Hepa-1c1c7 cells might be an antagonism of the DRE-binding potential of the
      nuclear Ah receptor, but is not mediated through the estradiol receptor.

PMID- 11248425
TI  - Nuclear BAG-1 localization and the risk of recurrence after radiation therapy in
      laryngeal carcinomas.
AB  - BAG-1 is a multifunctional chaperone modulator may contribute to p53-mediated
      cell cycle arrest. We attempted to investigate whether BAG-1 expression is
      correlated with prognosis of laryngeal carcinoma patients after radiotherapy.
      Immunohistochemical analyses revealed BAG-1 expression was present in all
      laryngeal carcinomas examined, and its expression pattern varied, i.e.
      cytoplasmic, nuclear and both these staining types. Patients whose tumors
      predominantly express nuclear BAG-1 have a significantly poor failure-free
      survival rate after radiotherapy. We thus propose that nuclear BAG-1 localization
      is a prediction of unfavorable outcome should radiation therapy be undertaken for
      laryngeal carcinoma patients.

PMID- 11248426
TI  - Differential anthracycline sensitivity in two related human colon carcinoma cell
      lines expressing similar levels of P-glycoprotein.
AB  - Chemosensitivity of the human colon carcinoma HCT-15 cell line to 4'
      epidoxorubicin proved to be 100-fold higher than that of its variant HCT-15 EDR.
      Confocal scanning microscopy showed significant less drug accumulation in HCT-15
      EDR. A 2-fold increase in hsp27 expression was found in HCT-15 EDR, with no
      alteration in hsp70. The expression of the drug exporter Pgp was similar in both
      cell lines, despite the lower drug accumulation shown by HCT-15 EDR in respect to
      HCT-15. Other molecules implicated in the acquisition of enhanced chemoresistance
      or a more active Pgp variant present in HCT-15 EDR, could explain the phenomenon.

PMID- 11248427
TI  - Activation of gamma-aminobutyric acid(B) receptors by baclofen improves visual
      temporal property of relay cells in the cat lateral geniculate nucleus.
AB  - The role of gamma-aminobutyric acid(B) (GABA(B)) receptors in spatial and
      temporal properties of the neurons was investigated in the cat dorsal lateral
      geniculate nucleus (dLGN) using flashing spot and drifting grating stimuli.
      Iontophoresis of baclofen, the selective GABA(B) receptor agonist significantly
      decreased the spontaneous and visual evoked responses (decreased to 38+/-7%), in
      which only the sustained component was suppressed sharply. Baclofen affected
      neither the center-surround antagonism of receptive fields nor the optimal
      spatial frequency of stimulating gratings. However, baclofen shortened cells'
      response duration and elevated their temporal frequencies that evoked the maximum
      and the half maximum response. In contrast, 2-OH-sacrofen, a GABA(B) antagonist
      showed no significant effect on dLGN cells' spatio-temporal properties. In
      conclusion, the activation of GABA(B) receptors may improve the temporal response
      properties of dLGN cells' via the sustained pathway, rather than change the
      spatial properties.

PMID- 11248428
TI  - Laminin-5 promotes neurite outgrowth from central and peripheral chick embryonic
      neurons.
AB  - Laminin-5 (Ln-5) is an essential component of epithelial basal laminae that is
      also expressed in the developing nervous system. Here we use a convenient, simple
      and reproducible in vitro fluorescent assay to assess the neurite outgrowth
      promoting activity of purified Ln-5. Embryonic chick neurons from dorsal root
      ganglia, ciliary ganglia, and (to a lesser extent) retina extended neurites on Ln
      5, but the neurite outgrowth promoting activity was not as great as that of Ln-1
      or Ln-2. Neurons from diencephalon, telencephalon, and spinal cord did not
      respond to Ln-5.

PMID- 11248429
TI  - Magnetic resonance lipid signals in rat brain after experimental stroke correlate
      with neutral lipid accumulation.
AB  - Proton magnetic resonance spectroscopy (MRS) signals from lipids in brain have
      been observed to increase after ischemic brain injury. However, neither the
      chemical identity nor the cellular location of these lipids has been established.
      The aim of the present study was to identify the origin of MRS lipid signals in
      rat brain after temporary (90 min) middle cerebral artery occlusion (MCAO). Fatty
      acyl proton signals were detected by short-echo one and two dimensional (1)H MRS
      in superfused brain slices from the infarcted hemisphere 1-5 days after MCAO. The
      intensities of these signals were strongly correlated with the amount of
      triacylglyceride and cholesterol ester in lipid extracts from the samples
      (r(2)=0.96, P<0.05) and were not correlated with the amount of free fatty acids
      in the tissue. Histological staining of tissue revealed the presence of neutral
      lipid droplets in infarcted regions. Dual labeling by immunohistochemistry
      demonstrated that these droplets were localized to microglia/macrophage (OX-42
      labeled cells). These results strongly suggest that (1)H MRS lipid signals from
      brain after stroke arise from microglia/macrophage phagocytosis of cellular
      membranes.

PMID- 11248430
TI  - Antioxidants prevent ethanol-induced contractions of canine cerebral vascular
      smooth muscle: relation to alcohol-induced brain injury.
AB  - The present study was designed to test the hypothesis that alpha-tocopherol (Vit.
      E) and pyrrolidine dithiocarbamate (PDTC) might exert direct effects on alcohol
      induced contractions of canine basilar cerebral arteries. After precontraction of
      arterial ring segments with ethanol, PDTC (10(-8)-10(-6) M) and Vit. E (10(-6)
      10(-4) M) induced concentration-dependent relaxations of cerebral arteries,
      compared to untreated controls. The effective concentrations producing
      approximately 50% of the maximal relaxation responses (EC(50) values) were about
      2.48+/-0.09 x 10(-7) M for PDTC, and 1.87+/-0.10 x 10(-5) mM for Vit. E,
      respectively. Preincubation of these arterial rings with EC(50)'s of PDTC or Vit.
      E for 40 min attenuate markedly the contractions produced by alcohol, at
      concentrations of 1-400 mM. However, both PDTC and Vit.E do not relax equi-potent
      precontractions induced by either KCl or prostaglandin F(2alpha) (PGF(2alpha)) or
      inhibit their contractions. These data suggest that alcohol-induced contractions
      of cerebral arteries are mediated via excitation-contraction coupling pathways
      different from those used by KCl or receptor-mediated agonists such as
      PGF(2alpha). The present results, when viewed in light of other recently
      published data, suggest that antioxidants may prove useful in the amelioration
      and treatment of alcohol-induced brain damage and strokes.

PMID- 11248431
TI  - Phosphoramidon-sensitive endothelin-converting enzymes modulate cerebral blood
      flow and neural damage of hypoxic rats.
AB  - The enzymatic activity of endothelin-converting enzymes (ECE) was altered to
      determine the potential effect of endothelins (ET) on cerebral blood flow
      measured by laser Doppler flowmetry (CBF(LDF)) and the resultant neural damage of
      rats, made hypoxic via breathing 12% O(2) for 35 min. Intrastriatal
      administration of phosphoramidon (PRN, 5 microM), a dual inhibitor of ECE and
      neutral endopeptidase (NEP), significantly increased infarct volume to hypoxia
      with a significant attenuation of CBF(LDF). However, intrastriatal thiorphan
      (TRN, 5 microM), an inhibitor of NEP, had no effect on the CBF(LDF) responses or
      infarct volume induced by the hypoxic challenge. These findings showed that
      inhibition of ECE by PRN interfered with the vasodilator activity of ET to the
      hypoxic response that increased neural damage, thus suggesting that PRN-sensitive
      ECE is functionally active in the modulation of cerebral blood flow in rats
      undergoing hypoxia.

PMID- 11248432
TI  - Calcium/calmodulin-dependent protein kinase inhibition potentiates thapsigargin
      mediated cell death in SH-SY5Y human neuroblastoma cells.
AB  - We previously demonstrated a loss in Ca(2+)/Calmodulin-dependent protein kinase
      (CaM kinase) activity in SH-SY5Y undergoing thapsigargin-mediated apoptosis. To
      extend that finding we report that CaM kinase inhibition potentiates thapsigargin
      mediated cell death. CaM kinase inhibitor KN93 on its own exhibits little
      toxicity up to 10 mM, as measured by release of lactate dehydrogenase (LDH) into
      the culture medium. In SH-SY5Y cells pretreated with KN93 and the non-selective
      protein kinase inhibitor k252a and then treated with 2 mM thapsigargin, loss of
      viability is significantly greater than in cells treated with thapsigargin alone.
      Pretreatment with the pan-caspase inhibitor Z-D-DCB prevented the thapsigargin
      mediated increase in LDH release. Furthermore, thapsigargin-induced caspase-3
      like activation, demonstrated by poly(ADP)ribose polymerase cleavage and pro
      caspase-3 processing, was elevated in the presence of KN93.

PMID- 11248433
TI  - Neurosteroid-induced enhancement of glutamate transmission in rat hippocampal
      slices.
AB  - Pregnenolone sulfate, one of the most abundantly produced neurosteroids in the
      hippocampus, has well characterized effects at postsynaptic receptors including
      the N-methyl-D-asparate type of glutamate receptor. Little is known, however,
      about the mechanism of action of neurosteroids on the release of glutamate. In
      this study we describe a robust effect of pregnenolone sulfate at glutamatergic
      synapses in the CA1 region of the hippocampus. In particular, we found that
      pregnenolone sulfate enhances paired-pulse facilitation of EPSPs at the two major
      classes of ionotropic glutamate receptors with an EC(50)<1 microM. Thus, we
      propose a novel mechanism of action of neurosteroids in hippocampal neurons that
      involves the modulation of glutamate release.

PMID- 11248434
TI  - The expression profiles of neurotrophins and their receptors in rat and chicken
      tissues during development.
AB  - Neurotrophic factors are target-derived proteins that promote the survival and
      differentiation of the innervating neurons. Increasing evidence indicate the
      involvement of these factors and receptors during the formation and maturation of
      the neuromuscular junction. To gain further insight on the expression pattern of
      these factors and receptors in developing spinal cord and skeletal muscle during
      the critical stages of synapse formation, a systematic study was performed with
      chicken and rat tissues using Northern blot analysis. The expression of all the
      neurotrophins was detected in skeletal muscle early in development, coincidental
      with the appearance of their corresponding receptors in the spinal cord. Taken
      together, the similar regulatory patterns observed in both rat and chicken
      tissues suggest that the potential roles of neurotrophins at the neuromuscular
      synapse are conserved throughout evolution.

PMID- 11248435
TI  - Nucleus basalis Meynert lesions and the expression of nicotinic acetylcholine
      receptor proteins in the rat frontal cerebral cortex.
AB  - An important feature of cholinergic dysfunction in Alzheimer's disease (AD) is
      the degenerative loss of magnocellular cholinergic neurons in the basal nucleus
      of Meynert. In search for suitable animal models of Alzheimer dementia, rats with
      lesioned basal nuclei rats have been shown to display learning and memory
      disturbances. We here report on the quantitative assessment of the expression of
      the nicotinic acetylcholine receptor alpha4 protein in the rat frontal cerebral
      cortex following a unilateral lesion of the basal nucleus. Cortical alpha4
      isoform expression shows a significant increase on the lesioned vs. the non
      lesioned control side 1 week after lesioning. By contrast, no differences were
      observed 4 weeks after lesioning. In consideration of these results basal nucleus
      lesions appear as a questionable model of AD which in contrast to the present
      findings shows a decrease of cortical alpha4 nicotinic acetylcholine receptor
      protein expression.

PMID- 11248437
TI  - Expression of the extra-large G protein alpha-subunit XLalphas in neuroepithelial
      cells and young neurons during development of the rat nervous system.
AB  - XLalphas ('extra large' alpha) is a 78 kDa splice variant of the alpha-subunit of
      the heterotrimeric G protein, Gs (Nature 372 (1994) 804). Prompted by its
      neuroendocrine-specific tissue distribution in the adult (J. Biol. Chem. 275
      (2000) 33622) and its ability to activate adenylyl cyclase (J. Biol. Chem. 275
      (2000) 33633), we investigated the expression of XLalphas in the developing rat
      nervous system using immunofluorescence. Remarkably, XLalphas expression in the
      neural tube was found to begin at the onset of neurogenesis, being observed in a
      subset of mitotic neuroepithelial cells as well as in young neurons. At later
      developmental stages, XLalphas was associated with a subset of neurons in certain
      regions of the nervous system such as diencephalon, midbrain, hindbrain, spinal
      cord and sympathetic trunk. These results suggest a role of XLalphas in neuronal
      differentiation.

PMID- 11248436
TI  - Intrathecal magnesium sulfate attenuates algogenic behavior and spinal amino
      acids release after kainic acid receptor activation in rats.
AB  - Activation of N-methyl-D-asparate (NMDA) receptor and non-NMDA classes of
      glutamate receptors play a key role in spinal nociceptive processing. Using with
      a lumbar intrathecal (IT) catheter and a loop dialysis catheter in lightly
      anesthetized (1% isoflurane) rats, the effect of IT pre-treatment with magnesium
      sulfate (100, 300 or 500 microg) on IT kainic acid (KA: 1 microg; non-NMDA
      receptor agonist) evoked amino acids (AAs) release and corresponding behavior was
      examined. IT KA produced significant increases (mean+/-SD of % baseline
      concentration) in dialysate concentrations of aspartate (424+/-88%), glutamate
      (241+/-35%) and taurine (398+/-58%). IT pre-treatment with MgSO(4) resulted in a
      dose-dependent suppression of the evoked algogenic behavior and aspartate
      release. These data suggest that activation of spinal KA receptors provides a
      powerful stimulus for secondary spinal excitatory AAs release and corresponding
      appearance of pain behavior. The regulation of this release by magnesium suggests
      the possible role of this divalent cation in regulating this excitatory effect of
      non-NMDA receptor activation.

PMID- 11248438
TI  - Intracerebroventricular injection of ghrelin and growth hormone releasing factor
      inhibits food intake in neonatal chicks.
AB  - Growth hormone releasing factor (GRF) is known to stimulate feeding of rats.
      Ghrelin, a novel growth hormone (GH)-releasing acylated peptide, was recently
      isolated from rat stomach. It also stimulates the release of GH from the anterior
      pituitary through the GH secretagogue receptor (GHS-R) and feeding in the rat. We
      have investigated the effects of ghrelin and GRF on food intake of the neonatal
      chick. In Experiment 1, 0, 1.25, 2.5 and 5 microg of ghrelin were administered
      intracerebroventricularly (i.c.v.) to ad libitum fed birds. In Experiment 2, the
      effect of (i.c.v.) injection of 0, 1.25, 2.5 and 5 microg of GRF was
      investigated. Both peptides strongly inhibited food intake of the chick during
      the 2-h post-injection period. In the third experiment, 0, 0.5, 1 and 2 microg of
      ghrelin was injected i.c.v. in chicks previously deprived of food for 3 h. Food
      intake was again inhibited by ghrelin in a dose-dependent manner. These results
      suggest that the mechanisms for feeding of the neonatal chick through GH release
      are different from mammals.

PMID- 11248439
TI  - Changes in post-tetanic potentiation of A-fiber dorsal horn field potentials
      parallel the development and disappearance of neuropathic pain after sciatic
      nerve ligation in rats.
AB  - Significant plastic changes in spinal nociceptive processing appear to accompany
      peripheral nerve injury or inflammation. Using a well-established model of
      neuropathic pain, we have recently reported that loose ligation of the sciatic
      nerve was accompanied by a long-lasting post-tetanic potentiation of sciatic
      evoked A-fiber superficial dorsal horn field potentials. In the present study we
      demonstrate that the typical disappearance of thermal hyperalgesia as a
      behavioral sign of neuropathic pain several weeks after loose sciatic nerve
      ligation is accompanied by the loss of the long-lasting potentiation. These data
      suggest that a significant but reversible shift in the processing of sensory
      information in the spinal dorsal horn follows peripheral nerve injury, and lend
      further support to the notion that long-lasting synaptic plasticity may
      contribute to the development of neuropathic pain.

PMID- 11248440
TI  - Persistent c-fos expression and NADPH-d reactivity in the medulla and the lumbar
      spinal cord in rat with short-term peripheral anosmia.
AB  - Here we examine hypothesis that short-term peripheral ZnSO(4)-induced anosmia can
      produce effects on c-fos expression within spinal cord and caudal medulla in male
      Wistar rats (n=4). Fos-like-immunoreactive cells revealed by avidin-biotin
      peroxidase method show a significant bilateral increase in the nucleus proprius
      (layers 3 and 4) and medial part of layers 5 and 6. In substantia gelatinosa
      (layer 2(i)) and area 10 Fos-positive neurons were intermixed together with
      nicotin-amide adenine dineucleotide phosphate-diaphorase (NADPH-d)-reactive
      cells. Short-term anosmia enhanced c-fos expression in ventral horn (layers 7 and
      8), ventrolateral segment and dorsal part of the spinal trigeminal nuclei. In
      anosmic rats varicose fibres and numerous NADPH-d-stained neurons were present in
      the gelatinous layer of the spinal trigeminal nucleus caudalis, and a separate
      population of Fos-positive cells was detected within this layer. Nucleus tractus
      solitaris also contained a few NADPH-d-reactive, medium sized neurons intermixed
      with Fos-immunoreactive cells.

PMID- 11248441
TI  - Prenatal cigarette smoke exposure selectively alters protein kinase C and nitric
      oxide synthase expression within the neonatal rat brainstem.
AB  - Maternal smoking is a major risk factor for sudden infant death syndrome. Protein
      kinase C (PKC) and neuronal nitric oxide synthase (NOS) activities within the
      dorsocaudal brainstem (DB) mediate critical components of respiratory drive and
      could be implicated in SIDS. Thus, exposure to smoking during fetal life could
      modify the expression of these kinases in the DB. Rats were exposed to cigarette
      smoke or room air (Sham) from day 2 to 22 of pregnancy. Immunoblots of DB lysates
      at 2 days postnatally revealed no differences in PKC-alpha, PKC-beta, and
      endothelial NOS expression. However, PKC-gamma, PKC-delta, and neuronal NOS
      immunoreactivities were reduced in the cigarette smoke group. We conclude that
      gestational smoking is associated with selective reductions in PKC and NOS
      isoforms within the DB, which could decrease respiratory drive and lead to
      enhanced hypoxic vulnerability in infants of smoking mothers.

PMID- 11248442
TI  - The alterations of N-Methyl-D-aspartate receptor expressions and oxidative DNA
      damage in the CA1 area at the early time after ischemia-reperfusion insult.
AB  - Delayed neuronal death in the CA1 of the hippocampus following global ischemia
      has been evoked by both the activation of N-methyl-D-aspartate receptor (NR) and
      the generate reactive oxygen species in the neurons. In the present study, we
      investigated whether oxidative DNA damages may be correlated with NR subunits
      (NR1 and NR2A/B) expression following ischemia insults in vivo. Thirty minutes
      after ischemia-reperfusion, the intensities of both NR and 8-hydroxy-2'
      deoxyguanosine (8-OHdG) immunoreactivities were markedly increased in neurons of
      CA1. However, NR2A/B and 8-OHdG immunoreactivities were enhanced in CA1 over 24 h
      after ischemia although NR1 immunoreactivity was decreased. These results suggest
      that oxidative stress and excitotoxicity in the CA1 may simultaneously trigger
      neuronal damages at early time after ischemia, and free radical damage including
      oxidative DNA damage may eventually promote the delayed neuronal death in this
      region.

PMID- 11248443
TI  - Site-dependent effects of an acute intensive exercise on extracellular 5-HT and 5
      HIAA levels in rat brain.
AB  - Previous neurochemical studies have reported different pattern of 5-HT release
      during exercise varying across either exercise conditions or forebrain sites.
      This in vivo microdialysis study is the first to examine the impact of an acute
      intensive treadmill running (2 h at 25 m.min(-1), which is close to exhaustion
      time), on extracellular 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid
      (5-HIAA) levels in two different brain areas in rats, the ventral hippocampus and
      the frontal cortex. Hippocampal and cortical 5-HT levels increased significantly
      after 90 min of exercise and were maximal in the first 30 min of recovery.
      Thereafter, cortical 5-HT levels followed a rapid and significant decrease when
      hippocampal levels are still maximal. During exercise, changes in extracellular 5
      HIAA levels paralleled 5-HT changes, but showed no difference between the two
      brain areas during recovery. Thus, an intensive exercise induces a delayed
      increase in brain 5-HT release but recovery seems to display site-dependent
      patterns.

PMID- 11248445
TI  - Implicit sub-unit learning in a serial reaction time task in humans.
AB  - In the present serial reaction time task experiment (SRT), a fixed 12-item
      sequence was practiced in order to evaluate the effect on response times to 3
      item sub sequences (triplets) in a subsequent random sequence. Subjects were
      visually cued to press one out of four keys with a corresponding right-hand
      finger. The occurrence of implicit sequence knowledge was evidenced by the
      increase in mean response time when the transition was made from the final 12
      item sequence block to the subsequent random block. In the stimulus-set applied,
      a total of 36 triplets could be constructed, of which 24 triplets were
      encountered only during the random blocks (random-only triplet set) (RO-set),
      whereas 12 triplets were also part of the sequence used in the sequence blocks
      (sequence-also triplet set) (SA-set). Approximately 35% of the triplets that
      comprised the two random blocks were also presented in the sequence blocks. There
      was no difference in mean response times between the triplet sets in the random
      block that preceded the sequence blocks. In the final random block, however, the
      SA-set induced significantly faster responses as compared with the RO-set. We
      argue that stimulus response associations within the SA-set are responsible for
      the difference in response times between the two triplet sets in the final random
      block.

PMID- 11248444
TI  - Modulation of the growth and guidance of rat brain stem neurons using patterned
      extracellular matrix proteins.
AB  - Dissociated neuronal cultures on substrates patterned with extracellular matrix
      (ECM) proteins have yielded much information regarding the physiological
      characteristics of neuronal cells behaviour in vitro. However, neuronal
      patterning using long term embryonic brain slice cultures has not been
      comprehensively demonstrated to-date. Structuring was performed by micro contact
      printing of laminin. The slice cultures were evaluated by means of phase contrast
      microscopy at 3-22 days in culture. We were able to consistently achieve
      outgrowth of neurons, neurites and filopodia from brain stem slices cultured on
      ECM proteins structures of grid- and line-shapes. We believe that brain slice
      cultures on patterned substrates is a favourable approach to study functional
      synapses in vitro under defined conditions. The use of appropriate structures and
      the subsequent cell patterning may help to gain further understanding of axonal,
      dendritic and synaptic signal transductions and processes.

PMID- 11248446
TI  - Y-chromosome variation in a Norwegian population sample.
AB  - Y-chromosome DNA profiles are promising tools in population genetics and forensic
      science. Here we present DNA profiles of 300 unrelated Y-chromosomes of Norwegian
      origin. The profile is composed of eight short tandem repeats (STRs) and one
      single nucleotide polymorphism (SNP). In more than 2/3 of the haplotypes the
      modular structure in the 5' end of the minisatellite locus DYF155S1 was revealed
      by minisatellite variant repeat PCR (MVR-PCR) These haplotypes were also typed
      for deletions of fragment 50f2C (DYF155S2). Allele distribution and paternity
      exclusion parameters are given for each marker. The degree of haplotype diversity
      and its implication for statistics are evaluated. In the 300 samples 177
      different haplotypes were encountered, of which 137 were observed once only.
      Analysis showed that the main source of variation is within the population. The
      Fst values were less than 0.015 in general. Haplotype grouping by the SNP
      demonstrated two haplogroups (Tat/T and Tat/C). Haplogroup Tat/C--found in 5.7%
      of the present material - is the same haplogroup as encountered in 60% of Finnish
      males [Am. J. Hum. Genet. 62 (1998) 1171]. Mutation analysis in 150 father/son
      pairs (a total of 1200 meiotic events) revealed an average mutation frequency of
      0.0042 (95% CI 0.0014-0.0097).

PMID- 11248448
TI  - Differential pulse anodic stripping voltammetry of barium and lead in gunshot
      residues.
AB  - Differential pulse anodic stripping voltammetry (DPASV) has been applied for
      characterization and quantitative detection of barium and lead from gunshot
      residues (GSR). Previous electrochemical techniques have detected antimony and
      lead from GSR, however barium has never been detected. This technique allows for
      simultaneous detection of Ba and Pb that is simple, fast, and nondestructive.

PMID- 11248447
TI  - Methadone and EDDP in hair from human subjects following a maintenance program:
      results of a pilot study.
AB  - A specific method has been developed for the quantitative determination of
      methadone (MTD) and its major metabolite, 2-ethylidene-1,5-dimethyl-3,3
      diphenylpyrrolidine (EDDP), in hair.An amount of 50mg hair samples were incubated
      in 0.01M HCl overnight at 60 degrees C and deuterated internal standards of MTD
      and EDDP were added before extraction. Hydrolyzed solutions were extracted by
      automated solid-phase extraction procedure and analyzed on a gas chromatography
      (GC) coupled to a ion trap mass spectrometer (MS). Positive chemical ionization
      was used with acetonitrile as liquid reagent. The different validation
      parameters, linearity, repeatability, recovery and detection limits are
      presented. A relative standard deviation (R.S.D.) of 12 and 11% was obtained for
      the repeatability of MTD and EDDP, respectively. The limits of quantification
      (LOQ) was 0.05ng/mg for MTD and 0.2ng/mg for EDDP.A number of 26 hair samples
      from human subjects following a long-term MTD therapy were analyzed by this
      method. Blood samples of these subjects were analyzed with a routine method using
      a liquid-liquid extraction and GC/nitrogen phosphorus detector (NPD). MTD was
      quantified in blood and hair samples and EDDP found in 50% of the hair sample.A
      comparison was made between the concentrations found in blood or in hair and the
      dose administrated. This study could demonstrate that there is no relation
      between the administrated dose and MTD or EDDP concentrations in hair.

PMID- 11248449
TI  - Congestion bleedings of the face and cardiopulmonary resuscitation--an attempt to
      evaluate their relationship.
AB  - OBJECTIVES: Are any other factors besides the factor "cause of death" involved in
      the development of petechial hemorrhages (PET) of the head? The significance of
      the cause of death is well known, other factors have been rarely investigated in
      medical literature. Do they include cardiopulmonary resuscitation (CPR), as has
      been claimed in several forensic publications? MATERIALS AND METHODS: (a) 473
      consecutive autopsy cases (without strangulation) evaluated by one examiner,
      which were appropriate for this investigation; (b) analysis of 181 cardiac deaths
      (investigated by all physicians of our institute). RESULTS: Petechiae were found
      in 13.3% of all cases and were clearly dependent on the cause of death, up to 20%
      were found in burn victims, intensive-care patients and cardiac fatalities.
      Petechiae were more frequently observed in the middle age groups (>20%) than in
      old persons (<10%). The number of PET cases increased with body mass but was
      lower in extremely obese persons, a greater number of cases with PET was also
      observed with increasing heart weight. PET were observed in 11% of the deaths
      without CPR compared to 19% with CPR. This difference was predominantly caused by
      the subgroup "acute coronary death", especially if victims younger than 60 years
      were considered, whereas in many other causes of death no difference in the
      prevalence of PET with or without CPR could be observed. CONCLUSION: Besides the
      cause of death, other factors (age, body mass and possibly even heart weight)
      influence the development of petechiae. The hypothesis that CPR alone produces
      PET is not confirmed by our experience.

PMID- 11248450
TI  - Intra-familial child homicide in Finland 1970-1994: incidence, causes of death
      and demographic characteristics.
AB  - The purpose of this study was to investigate all child homicides for the 25-year
      period, 1970-1994 in Finland and to analyse the specific characteristics of the
      filicide cases. A total of 292 child homicides occurred during this period. In
      201 (69%) cases the offender was a parent or a stepparent of the child.
      Altogether, 173 (59%) of the victims were boys and 119 (41%) were girls. For the
      closer examination of the filicide cases we excluded the neonaticide and homicide
      suicide cases. Consequently, we report on 70 filicide victims. Of these victims,
      42 (60%) were boys and 28 (40%) were girls. Twenty six (37%) of the children were
      killed before the age of 1 year and 53 (79%) before the age of 5 years. The
      offender was the mother in 43 (61%) cases and the father or the stepfather in 26
      (37%) cases. The victims of the mothers were younger than those of the fathers.
      The most frequent causes of death were head injuries, drowning and suffocation.
      The most common means of assault were battering, drowning and strangulation. One
      in two of the fatally battered children had a documented history of previous
      abuse.

PMID- 11248451
TI  - Immunohistochemical investigation of pulmonary surfactant-associated protein A in
      fatal poisoning.
AB  - To evaluate the immunohistochemical distribution of pulmonary surfactant
      associated protein A (SP-A) in fatal poisoning in relation to the effects of
      drugs and poisons on respiratory function, 42 forensic autopsy cases were
      examined by scoring the staining intensity. The highest scores of SP-A staining,
      with dense granular deposits (aggregates) in the intra-alveolar space, were
      observed in fatalities from pancuronium bromide (muscle relaxant) injection and
      petroleum (butane) gas inhalation. Poisoning with organophosphate pesticides and
      arsenic (ingestion) showed a second grade SP-A score. However, The SP-A scores
      were relatively low in ethanol and sedative-hypnotic intoxication. Carbon
      monoxide intoxication showed a varied degree of SP-A score, and the aggregated SP
      A score tended to be higher in cases of lower blood carboxyhemoglobin
      concentration. A varied SP-A score was also observed in methamphetamine
      fatalities, in which the score was relatively low in cases with a higher serum
      drug level. Increase of SP-A was not always associated with the intra-alveolar
      effusion or hemorrhages. The above-described observations suggested that the
      immunohistochemical score of SP-A may be a possible indication for intensity and
      duration of drug/poison-dependent respiratory distress.

PMID- 11248452
TI  - Development of rigor mortis is not affected by muscle volume.
AB  - There is a hypothesis suggesting that rigor mortis progresses more rapidly in
      small muscles than in large muscles. We measured rigor mortis as tension
      determined isometrically in rat musculus erector spinae that had been cut into
      muscle bundles of various volumes. The muscle volume did not influence either the
      progress or the resolution of rigor mortis, which contradicts the hypothesis.
      Differences in pre-rigor load on the muscles influenced the onset and resolution
      of rigor mortis in a few pairs of samples, but did not influence the time taken
      for rigor mortis to reach its full extent after death. Moreover, the progress of
      rigor mortis in this muscle was biphasic; this may reflect the early rigor of red
      muscle fibres and the late rigor of white muscle fibres.

PMID- 11248453
TI  - A biomechanical reconstruction of a wound caused by a glass shard--a case report.
AB  - During the course of a criminal trial, an investigating pathologist is commonly
      asked how much force was required to produce an injury. This subjective opinion
      is based on the pathologist's previous experience of dealing with wounds
      inflicted with similar weapons. However, in the case of stab wounds inflicted by
      broken glass, it is unlikely that two glass fragments would be physically
      similar. In the case studied, two theories were examined: that a wound resulted
      from a thrown glass fragment or that it had been caused as a stab injury by the
      glass held in the bare hand. The investigation involved quantifying the energy
      required for human tissue penetration, comparison of sharpness, a biomechanical
      analysis of throwing actions and testing of the hypothesis that if the glass
      shard were used as a stabbing implement it would result in a cut to the hand.The
      investigation utilised a scientific methodology that reduced the need for
      speculative (though informed) opinion from the pathologist by producing
      quantitative results.

PMID- 11248454
TI  - STR population data for 10 STR loci including the GenePrint PowerPlex 1.2 kit
      from El-Minia (Central Egypt).
AB  - Allele frequencies for 10 STRs including the GenePrint PowerPlex 1.2 loci and
      also D3S1358, HumvWA and HumFGA were obtained from a sample of unrelated
      individuals from El-Minia City.

PMID- 11248455
TI  - Population data of F13AO1, FES/FPS, VWA, CSF1PO, TPOX and THO1 short tandem
      repeat loci in a sample of African descent individuals of Colombia.

PMID- 11248456
TI  - Mutism: elective or selective, and acquired.
AB  - When a child does not speak, this may be because there is no wish to do so
      (elective or selective mutism), or the result of lesions in the brain,
      particularly in the posterior fossa. The characteristics of the former children
      are described, especially their shyness; and it is emphasized that mild forms are
      quite common and a definitive diagnosis should only be made if the condition is
      significantly affecting the child and family. In the case of mutism due to
      organic causes, the commonest of these is trauma to the cerebellum. Operations on
      the cerebellum to remove tumours can be followed by mutism, often after an
      interval of a few days, and it may last for several months or longer, to be
      followed by dysarthria. Other rarer causes are discussed, and also the
      differential diagnosis. The so-called posterior fossa syndrome consists of mutism
      combined with ataxia, cranial nerve palsies, bulbar palsies, hemiparesis,
      cognitive impairment and emotional lability, but the post-operative symptoms are
      often dominated by the lack of speech. The most accepted cause for the condition
      is vascular spasm with involvement of the dentate nucleus and the
      dentatorubrothalamic tracts to the brain-stem, and subsequently to the cortex.
      Diaschisis may be involved in causing the loss of higher cerebral functions, and
      possibly, complicating hydrocephalus. The treatment of elective mutism is
      reviewed, either using a psychotherapeutic approach or a variety of drugs, or
      both. These may well be ineffective, and it must be remembered that the condition
      often resolves on its own. The former treatment must concentrate on the training
      of social skills and activities of daily life and must be targeted to both the
      child, the family, and the school. Also, all kinds of punishment and insistence
      on speech must be discouraged. The drug, which seems to be most effective, is
      fluoxetine. Discovering more about the causes of mutism due to organic causes may
      well depend on studies using such techniques as magnetic resonance imaging and
      single photon emission tomography.

PMID- 11248457
TI  - Neurocognitive development of children with congenital unilateral brain lesion
      and epilepsy.
AB  - The aim of this study was to specify the neuropsychological deficits
      characteristic of children with unilateral non-progressive brain lesion. In order
      to assess these specific functions, we used a comprehensive model of congenital
      hemiparesis with partial epilepsy and newly diagnosed partial epilepsy without
      hemiparesis. The neuropsychological examination was performed using the NEPSY
      test battery on 44 children aged from 4 to 9 years. The children were divided
      into three groups: 18 children suffering from congenital hemiparesis with chronic
      partial epilepsy, 12 children with newly diagnosed partial epilepsy prior to anti
      epileptic treatment, and 14 healthy controls matched by sex, age, and
      socioeconomic status. Children with congenital hemiparesis and epilepsy had a
      more clearly expressed cognitive dysfunction, especially in language, visuo
      perceptual and memory tasks, than children with newly diagnosed partial epilepsy.
      The profile of cognitive weakness appears to be diffuse and quite similar in both
      groups, and it did not demonstrate a clear effect of lateralization, according to
      the side of epileptic electroencephalogram discharges. Children within both
      groups are likely to have a high risk of developing attention, phonological,
      visuo-perceptual, and memory deficits in their life. Especially interesting and
      surprising was the fact that the newly diagnosed epilepsy group demonstrated
      impairment not only in attention, visuo-perceptual and short-term memory skills,
      but also in auditory perception, lexical function, and the comprehension of
      speech. Therefore, it is recommended that children with epilepsy would undergo
      neuropsychological examination in order to assess their cognitive abilities.

PMID- 11248458
TI  - Clinicopathological study on eyes from cases of Fukuyama type congenital muscular
      dystrophy.
AB  - Fukuyama type congenital muscular dystrophy (FCMD) is an autosomal recessive
      disorder characterized by progressive muscular dystrophy and dysgenesis of the
      central nervous system and eyes. To clarify the pathomechanism of the ocular
      involvement in FCMD, we performed postmortem pathological analyses of eyes from
      three postnatal FCMD cases, two fetal FCMD cases, and three control cases by
      macroscopic, histopathological, immunohistochemical and in situ hybridization
      approaches. The macroscopic and histopathological examinations revealed a variety
      of ocular abnormalities such as folding, fusion or dysplasia of the retinas in
      the FCMD cases both with and without ophthalmological alterations.
      Immunoreactivities for collagen IV and laminin, produced by Muller cells, as the
      basement membrane components, were less intense in the inner limiting membrane of
      the FCMD retinas than in that of the control retinas. A number of the
      perivascular glial cells containing S-100 protein and glial fibrillary acidic
      protein were increased in the postnatal FCMD cases. Immunoreactivities for
      vimentin, glutamate transporter-1, glutamine synthase and ornithine
      aminotransferase, expressed in the Muller cells, were undetectable in the fetal
      FCMD retinas, and reduced in the postnatal FCMD retinas compared with the control
      retinas. Fukutin mRNA signals were distributed diffusely in the retinoblast layer
      of the control retinas, focally in the retinoblast layer of the fetal FCMD
      retinas, and only in the dysplastic areas with rosette formation of the postnatal
      FCMD retinas, composed of retinoblasts and other retinal cells including the
      Muller cells. The present findings suggest that the Muller cells are implicated
      in the retinal pathology of FCMD.

PMID- 11248459
TI  - Ataxia and congenital muscular dystrophy: the follow-up of a new specific
      phenotype.
AB  - Cerebellar hypoplasia may, at neuroimaging studies, be found in association with
      congenital muscular dystrophy (CMD), although it is an extremely rare occurrence.
      We here report on three CMD patients who underwent a longitudinal evaluation of
      clinical and neuroimaging features for a mean period of 18 years. Case 1, a 22
      year-old woman, and cases 2 and 3, brothers aged 26 and 20 years, respectively,
      had presented a mild to moderate muscular weakness and increased serum creatine
      kinase (CK) levels since birth. All cases were diagnosed in the first years of
      life, with identification of evident dystrophic changes at muscle biopsy and
      moderate to severe cerebellar hypoplasia at brain computed tomography (CT) scan.
      Subsequently, all the patients underwent a second muscle biopsy, with
      immunostaining and immunoblot analysis, which showed normal values for merosin,
      dystrophin and dystrophin-related proteins. During the longitudinal study, the
      patients underwent repeated neurological and psychiatric examinations, serum CK
      controls, intellectual ability assessments and neuroimaging evaluations (CT
      and/or magnetic resonance imaging (MRI)). In all cases, these investigations
      indicated a mild to moderate deficit in the proximal muscles and a clear-cut
      cerebellar syndrome which, it was assumed, had been present since the first
      years. The patients also presented some intellectual difficulties, with an IQ of
      0.69 in case 1, 0.83 in case 2 and 0.61 in case 3. The clinical course of all the
      patients was static, and all symptoms of the combined muscle and brain
      involvement persisted. Nor were any changes in the cerebellar hypoplasia observed
      at repeat MRIs. Findings obtained by us on the longitudinal study and a review of
      the literature indicate that cerebellar hypoplasia and merosin-positive CMD
      constitute a particular clinical phenotype, mainly characterized by an ataxic
      syndrome associated with a non-severe muscular involvement and a possible mild
      intellectual impairment.

PMID- 11248460
TI  - Electroencephalographic changes and their regional differences during pediatric
      cardiovascular surgery with hypothermia.
AB  - Monitoring brain function by EEG is an important means of preventing cerebral
      insults in pediatric cardiovascular surgery. We studied intraoperative EEG
      changes and their regional differences associated with hypothermia and brain
      ischemia. The subjects of this study consisted of 13 children ranging in age from
      4 months to 4 years and 6 months. Multi-channel EEGs were recorded using a
      portable digital EEG system, and the EEG changes were examined by visual
      inspection and computerized analyses. The results were as follows. (1) During
      cooling, a discontinuous EEG pattern was transiently observed in four patients,
      and this phenomenon indicated rapid suppression of cerebral function and
      subsequent adaptation. (2) Regarding the patterns of change in equivalent
      potentials induced by hypothermia, there were two different patterns depending on
      the degree of hypothermia, and the borderline rectal temperature was found to be
      around 32 degrees C. (3) During cooling, regional differences in the changes in
      equivalent potentials were observed in nine patients. A decrease in slow waves
      was marked in the occipital head area, and a decrease in fast waves was prominent
      in the anterior head area. (4) Arterial hypotension caused transient EEG
      abnormalities. Of them, bilaterally synchronous rhythmic high voltage slow waves
      were remarkable and exhibited bifrontal or bicentral dominance. (5) The EEG
      changes induced by hypothermia were influenced not only by the rectal temperature
      itself, but also by the rate of change in rectal temperature, and we speculated
      that this phenomenon was a result of adaptation. In intraoperative EEG
      monitoring, these findings constitute the basis for early detection of a cerebral
      hypoxic-ischemic state during pediatric cardiovascular surgery.

PMID- 11248461
TI  - Occlusive hydrocephalus in congenital myotonic dystrophy.
AB  - A case of congenital myotonic dystrophy is reported which was complicated by the
      development of a hydrocephalus that needed ventricular-peritoneal shunting at the
      age of 4 months. Although dilatation of cerebral ventricles is a common feature
      in these patients, an occlusive hydrocephalus has not so far been reported.

PMID- 11248462
TI  - Papillitis as an onset sign of Leber's hereditary optic neuropathy: a case
      report.
AB  - Leber's hereditary optic neuropathy is a maternally transmitted disease resulting
      from a point mutation in mitochondrial (mt) DNA. In this report we describe a
      case of Leber's disease with typical clinical findings but atypical
      ophthalmoscopic presentation. A 14-year-old boy developed severe loss of vision
      acuity in the left eye, with only partial recovery, followed 4 months later by
      the same symptoms in the right eye. Fundoscopic examination showed hyperemic
      papilla on the right eye and optic disc pallor on the left eye. Polymerase chain
      reaction analysis of lymphocytic mt-DNA revealed a point mutation at 11778.
      Leber's disease should be considered in young patients (not always male) with
      sudden visual loss and simple papillary involvement at fundoscopic examination
      but without the typical telangiectatic microangiopathy.

PMID- 11248463
TI  - The first case of 4-hydroxybutyric aciduria in Japan.
AB  - We report a boy with 4-hydroxybutyric aciduria resulting from a deficiency of
      succinic semialdehyde dehydrogenase (SSADH). A boy, 1 year 5 months, showed
      delayed walk with hypotonia and could not speak meaningful words. The blood
      levels of lactate, pyruvate and amino acids were not elevated. Head magnetic
      resonance imaging (MRI) and electroenchephalography (EEG) were normal. Urinary
      organic acid analysis with gas chromatography-mass spectrometry (GCMS) revealed
      increased levels of 4-hydroxybutyric acid, glutaric acid, adipic acid and suberic
      acid. The concentrations of 4-hydroxybutyric acid and gamma-aminobutyric acid
      (GABA) were elevated in the serum and cerebrospinal fluid (CSF). SSADH activity
      in cultured lymphoblasts was 4.5% of the normal level. So far as we know this is
      the first Japanese patient diagnosed as 4-hydroxybutyric acid. Urinary organic
      acid analysis is necessary for the diagnosis of patients with unexplained
      psychomotor retardation.

PMID- 11248464
TI  - A variant case of congenital bilateral perisylvian syndrome with asymmetric
      findings on neuroimaging and septum pellucidum defect.
AB  - We report a 17-year-old female patient with a variant form of congenital
      bilateral perisylvian syndrome (CBPS). She had pseudobulbar palsy, partial
      epilepsy and mild pyramidal symptoms predominantly in the left hand. Magnetic
      resonance imaging revealed asymmetric perisylvian and perirolandic polymicrogyric
      cortical dysplasia and septum pellucidum defect. The clinicoradiological findings
      for this patient met the criteria for CBPS. Moreover, they appeared to overlap
      those of congenital unilateral perisylvian syndrome. The findings in this case
      support the hypothesis that these two syndromes are parts of a continuous
      spectrum of one clinico-radiological syndrome.

PMID- 11248465
TI  - Alleviation of sleep disturbance and repetitive behavior by a selective serotonin
      re-uptake inhibitor in a boy with Asperger's syndrome.
AB  - An 8 year-old boy with Asperger's syndrome had difficulties in communicating with
      his teachers and classmates. He occasionally stole out of the classroom. He could
      not sleep at night recalling his awful experience and kept crying every night and
      refused to go to school. The treatment with fluvoxamine was started at the dose
      of 25 mg daily. Four weeks after the treatment, his repetitive behavior and
      hyperactivity decreased and night crying diminished. Although he still has
      difficulties in communicating with others, he is now able to attend extra
      curricular classes in a private school. Fluvoxamine, a selective serotonin re
      uptake inhibitor that has been mainly used for patients with depression and
      obsessive-compulsive disorder, might be effective for compulsive symptoms and
      sleep disturbance of patients with pervasive developmental disorders.

PMID- 11248467
TI  - Guidance for robustness/ruggedness tests in method validation.
AB  - This paper is intended to give guidance in setting-up and interpreting a
      robustness test. The different steps in a robustness test are discussed and
      illustrated with examples. The recommendations given for the different steps are
      based on approaches found in the literature, several case studies performed by
      the authors and discussions of the authors within a commission of the French
      SFSTP (Societe Francaise des Sciences et Techniques Pharmaceutiques). In the end
      of the paper a worked-out example is given of a robustness test case study set up
      and interpreted according to the guidelines.

PMID- 11248468
TI  - Validation in pharmaceutical analysis. Part I: an integrated approach.
AB  - The ICH guidelines achieved a great deal in harmonising the definitions of the
      required validation characteristics and their basic requirements. However, they
      provide only a basis for a general discussion of the validation parameters, their
      calculation and interpretation. It is the responsibility of the analyst to
      identify parameters which are relevant to the performance of the given analytical
      procedure as well as to design proper validation protocols including acceptance
      criteria and to perform an appropriate evaluation. In order to fulfil this
      responsibility properly, the background of the validation parameters and their
      consequences must be understood. In this part, the general concept of an
      integrated validation is discussed. The interdependencies to other ICH guidelines
      and topics during drug development (e.g. impurities and degradants, stability and
      specification design) must be taken into account to define the required
      acceptance criteria. Evaluation of the results in order to prove the suitability
      of the analytical procedure must be based on the specification limits. Important
      parameters and aspects are discussed for the individual validation
      characteristics. In the following parts, these parameters will be discussed in
      detail. Examples will be given for their interpretation in order to facilitate
      the selection of parameters which are relevant to the performance and suitability
      of the given analytical procedure.

PMID- 11248469
TI  - The role of pharmacopoeias in international harmonisation.
AB  - The last 30 years have seen profound changes in the organisation of the European
      people and the regulation of medicinal products. Thirty years ago, each country
      had its own regulations, with all the possible variations between the various
      national pharmacopoeias. Today, the European Pharmacopoeia, with its 1500
      monographs and nearly 250 general methods of analysis, has replaced the major
      part of these national regulations: the European Pharmacopoeia Convention has now
      been signed by 27 states(1) and by the Commission of the European Communities;
      moreover 16 European and non-European countries(2) and the WHO have observer
      status. Close relations are maintained with the licensing authorities of the
      European Economic Area, where integration is developing via the implementation of
      common directives and guidelines on medicines for human and veterinary use. In
      addition, in 1990, the European Pharmacopoeia co-founded, with the Japanese
      Pharmacopoeia and the US Pharmacopoeia, the Pharmacopoeial Discussion Group
      (PDG); this group is working assiduously for harmonisation at world level.

PMID- 11248470
TI  - High-throughput assays on the chip based on metal nano-cluster resonance
      transducers.
AB  - High throughput transducers using metal cluster resonance technology are based on
      surface-enhancement of metal cluster light absorption. These devices can be used
      for detection of biorecognitive binding, as well as structural changes of nucleic
      acids, proteins or any other polymer. The optical property for the analytical
      application of metal cluster films is the so-called anomalous absorption. An
      absorbing film of clusters positioned 10--400 nm to a mirror surface reacts in a
      similar way to a reflection filter. At a certain distance of the absorbing layer
      to the mirror the reflected electromagnetic field has the same phase at the
      position of the absorbing cluster as the incident fields. This feedback mechanism
      strongly enhances the effective cluster absorption coefficient. The system is
      characterised by a narrow reflection minimum whose spectral position shifts
      sensitively with the interlayer thickness, because a given cluster-mirror
      distance and wavelength defines the optimum phase. Based on this principle a set
      of novel tools including biochips and micro arrays is presented, which enabled us
      to transduce binding, as well as changes of protein-, DNA- and polymer
      conformation, quantitatively into an optical signal which can be observed
      directly as a colour change of a sensor-chip surface.

PMID- 11248471
TI  - Capillary electrophoretic separation, immunochemical recognition and analysis of
      the diastereomers quinine and quinidine and two quinidine metabolites in body
      fluids.
AB  - The capillary electrophoretic separation and immunochemical recognition of the
      two naturally fluorescing, cationic diastereomers quinine (QN) and quinidine
      (QD), their hydroderivatives and two major QD metabolites (3-hydroxyquinidine and
      quinidine-N-oxide) was investigated. Plain aqueous phosphate buffers and an
      alkaline buffer containing dodecyl sulfate micelles are shown to be incapable of
      resolving the two diastereomers. However, incorporation of an additional chemical
      equilibrium (with beta-cyclodextrin) in the case of capillary zone
      electrophoresis (CZE) and the presence of a small amount of an organic solvent as
      buffer modifier (2-propanol) in dodecyl sulfate based micellar electrokinetic
      capillary chromatography (MECC), were found to provide separation media which
      lead to complete resolution of QN, QD and the other compounds of interest.
      Furthermore, for MECC- and CZE-based immunoassay formats, a commercially
      available antibody against QD was found to be a perfect discriminator between QD
      and QN. It was determined to recognize QD and the two QD metabolites (cross
      reactivity of 20--30%) but not QN. MECC and CZE with laser induced fluorescence
      (LIF) detection are shown to be suitable to determine QD and metabolites in urine
      and plasma (quinidine-N-oxide only) collected after single dose intake of 50 mg
      QD sulfate and of QN in urine, saliva and serum samples that were collected after
      self-administration of 0.5 l of quinine water (25 mg of QN). With direct
      injection of a body fluid, MECC with LIF was found to provide 10 ng/ml detection
      limits for QD and QN. This ppb sensitivity is comparable to that obtained in HPLC
      assays that are based upon drug extraction. Furthermore, MECC and CZE assays with
      UV detection are shown to provide the ppm sensitivity required for therapeutic
      drug monitoring and clinical toxicology of QD and QN.

PMID- 11248472
TI  - Development and validation of an automated method for the liquid chromatographic
      determination of sotalol in plasma using dialysis and trace enrichment on a
      cation-exchange pre-column as on-line sample preparation.
AB  - A fully automated method for the determination of sotalol in human plasma was
      developed, involving dialysis through a cellulose acetate membrane, clean-up and
      enrichment of the dialysate on a strong cation-exchange pre-column and subsequent
      liquid chromatographic (LC) analysis with UV detection. All sample handling
      operations were carried out by means of an ASTED system. Before starting
      dialysis, the trace enrichment column (TEC) was conditioned. The plasma sample,
      to which the internal standard (atenolol) was automatically added, was then
      loaded in the donor channel and was kept static while the dialysis liquid,
      consisting of 0.017 M acetic acid, was passed through the acceptor channel in
      successive pulses. After each pulse, the dialysate was dispensed onto the TEC.
      When dialysis was discontinued, the analytes were eluted from the TEC by the LC
      mobile phase by rotation of a switching valve and transferred to the analytical
      column packed with octyl silica. The LC mobile phase was a mixture of methanol
      and pH 7.0 phosphate buffer containing 1-octanesulfonate at a concentration of
      7.5 x 10(-4) M (19:81; v/v). The UV detection was performed at 230 nm. The
      influence of several parameters of the dialysis and trace enrichment processes on
      analyte recovery and method selectivity was investigated. The method was then
      validated. The mean absolute recovery for sotalol was about 60%. The limit of
      quantitation was 25 ng/ml and R.S.D. for repeatability and intermediate precision
      obtained at a concentration level of 50 ng/ml were 4.3 and 5.8%, respectively.

PMID- 11248473
TI  - Proteomics -- the protein expression technology to study connective tissue
      biology.
AB  - During the formation of peribronchial fibrosis in asthma, remodeling of
      connective tissue is due to an increase in deposition of extracellular matrix
      components like that of specific types of collagens and proteoglycans. By taking
      bronchial biopsies, we were able to isolate cell cultures derived from asthmatic
      patients and healthy volunteers, which provides a good model system to study
      differences regarding cell morphology and key connective tissue proteins in the
      remodeling process. Proteomics, utilizing two-dimensional electrophoresis and
      modern image analysis systems have made it possible to study protein expression
      and regulation of proteins in biological systems. By using this powerful tool, it
      is possible to quantitatively study protein regulation and to obtain increased
      knowledge about the mechanism behind the inflammatory process and formation of
      peribronchial fibrosis. We have optimized a proteomic protocol enabling detailed
      investigation of the protein expression pattern in human lung cells. An increased
      expression pattern was obtained, whereby 20 protein spots could be detected by
      image analysis in the <45 kDa region. Out of these, specific regulations of four
      spots were found by quantitative image analysis and spots of interest were
      identified by MALDI TOF-MS. This protocol enables us to study 1000--2000 proteins
      simultaneously and the possibility to correlate protein expression to the
      physiological status of the cell culture investigated. We have found that two
      proteins, actin and tropomyosin, are increased in expression due to transforming
      growth factor-beta stimulation. These proteins are correlated to the
      transformation of normal fibroblasts to myofibroblasts which are involved in the
      remodeling processes observed in asthma.

PMID- 11248474
TI  - (Immuno)affinity chromatography: a versatile tool for fast and selective
      purification, concentration, isolation and analysis.
AB  - Today, thanks to the availability of tailor made biomolecules with the desired
      biological functions, separations based upon (immuno)affinity techniques are more
      and more common in a large field of applications. By using the high selectivity
      of biomolecules (antibodies, receptors, specific proteins), this technique offers
      the possibility of isolating compounds from complex samples with a selectivity
      which cannot be achieved by other chromatographic methods. In order to succeed,
      however, the solid phase support for the immobilisation of the ligand of interest
      plays a prominent role. For this reason, numerous supports have already been
      introduced while research on new materials with additional advantages is
      continued. Here, a new solid phase support will be discussed for (immuno)affinity
      applications. This material demonstrates low non-specific adsorption and high
      ligand accessibility, which enables an enhanced selectivity and capacity. Because
      the material is available in large quantities and exhibits superb mechanical and
      physical stability, selective isolations have been performed on analytical as
      well as preparative scale. To demonstrate the potential of this new support,
      several applications will be presented. Based upon immunoaffinity, two
      applications for the determination of oestradiol in serum respectively vitamin
      B12 in fermentation broth will be presented. Regarding affinity chromatography,
      an enzyme reactor in which the enzyme glucose oxidase is immobilised on the new
      material, is made for the detection of glucose by Flow Injection Analysis and
      electrochemical detection. Next, to isolate, identify and test components on
      their xeno-oestrogenic activity, an affinity column is produced in which human
      oestrogen receptor is covalently coupled. Several components are screened on
      their biological activity and the results obtained will be presented here.

PMID- 11248475
TI  - Cystatin C, beta 2-microglobulin, and retinol-binding protein as indicators of
      glomerular filtration rate: comparison with plasma creatinine.
AB  - BACKGROUND: The aim of this study was to assess the diagnostic accuracy of plasma
      levels of three low-molecular weight proteins cystatin C, beta 2-microglobulin,
      and retinol-binding protein, as indicators of impairment of glomerular filtration
      rate in comparison with plasma creatinine. METHODS: Glomerular filtration rate
      (GFR) was measured in 110 patients (51 M and 59 F, aged 18--79 years); creatinine
      (Creat), cystatin C (Cys), beta 2-microglobulin (beta 2M), and retinol-binding
      protein (RBP) were determined on the same day. The correlation coefficients
      between the different markers and GFR were determined. Receiver-operating
      characteristics (ROC) analysis was performed to assess their diagnostic accuracy.
      Furthermore, the relationship between plasma levels of the examined markers of
      GFR and body weight, height, fat-free mass (FFM) and body cell mass (BCM) was
      determined. FFM and BCM were calculated by means of total body electrical
      impedance measurement. RESULTS: Serum concentrations of Cys, beta 2M and RBP
      increase progressively with the reduction of GFR. The magnitude of the increase
      in blood levels of Creat and beta 2M was higher than the increase of Cys, and
      much more than that of RBP, in particular in patients with GFR<20 ml/min/1.73
      m(2). The correlation coefficients between GFR and 1/plasma concentrations were
      0.647 for Creat, 0.651 for Cys, 0.731 for beta 2M, and 0.406 for RBP. ROC
      analysis indicated that the accuracy of beta 2M and Cys, as indicators of
      different degrees of GFR impairment (<80, <60, and <40 ml/min per 1.73 m(2)), was
      similar to that of Creat, while the diagnostic accuracy of RBP resulted
      significantly lower than that of Creat for any level of GFR. In patients without
      renal failure (GFR>40 ml/min per 1.73 m(2)), plasma concentrations of Creat were
      positively correlated with body weight (P<0.01), height (P<0.01), FFM (P<0.001)
      and BCM (P<0.001). Serum concentrations of RBP resulted correlated with FFM
      (P<0.05) and BCM (P<0.05), while no correlation was found between anthropometric
      data and Cys and beta 2M. CONCLUSION: Cystatin C and beta 2-microglobulin have a
      diagnostic accuracy very similar to that of creatinine, while retinol-binding
      protein is not an adequate marker of glomerular filtration.

PMID- 11248476
TI  - The evaluation of interdigitated array electrodes for measurement of
      catecholamines and indoleamines.
AB  - The use of Interdigitated Array (IDA) Microelectrodes for detection of low levels
      of biogenic amines has been demonstrated in stationary solutions and flow systems
      [M. Morita, et al., Electrochemica Acta 42 (20--21) (1997) 3177--3183]. This
      technique is highly sensitive. We have evaluated this technology as applied to
      High Pressure Liquid Chromatography with Electrochemical Detection (HPLC-EC) for
      analysis of microdialysate and tissue samples. With this new technology we
      demonstrated a x 10 fold increase in sensitivity in comparison to our existing
      technology. We are now able to detect dopamine at a level of 53 x 10(-18) moles
      on column and serotonin at 26 x 10(-18) moles on column. This technology now
      permits analysis of biogenic amines in samples from brain areas not previously
      amenable to this type of experiment.

PMID- 11248477
TI  - Capillary electrophoresis and high-performance anion exchange chromatography for
      monitoring caseinoglycomacropeptide sialylation.
AB  - Capillary zone electrophoresis was applied to separate caseinoglycomacropeptide
      glycoforms and characterize microheterogeneity of the glycopeptide. Particular
      attention was paid to the sialic acid content in caseinoglycomacropeptide
      obtained through different manufacturing processes. A chemometric approach was
      used to simultaneously study effects of acid concentration, hydrolysis time and
      temperature on sialic acid release from caseinoglycomacropeptide. Hydrolysis
      conditions that maximize sialic acid release were chosen. Sialic acid was
      determined using high performance anion exchange chromatography coupled with
      pulsed amperometric detection. Results were compared to those obtained by
      alternative techniques, such as colorimetric and enzymatic methods.

PMID- 11248478
TI  - Determination of 8-chloroadenosine 3',5'-monophosphate in dog plasma by capillary
      electrophoresis.
AB  - A method for the quantitative determination of 8-chloroadenosine 3',5'
      monophosphate (8-Cl-cAMP) in dog plasma by capillary zone electrophoresis (CE)
      has been developed and validated. Samples of plasma (with 2'-O
      monobutyryladenosine-3',5'-monophosphate as internal standard) were deproteinized
      with two volumes of acetonitrile. The supernatant was evaporated and
      reconstituted in water. A BioFocus 2000 system (Bio-Rad, Hercules, CA, USA) was
      used. The UV detector was set at 261 nm. The samples were loaded into uncoated
      fused silica capillary (40 cm x 50 microm) by pressure injection. A running
      electrolyte contained 30 mM SDS, 100 mM Tris, pH 7.55, with 20% of methanol
      added. The typical analytical conditions were: voltage, 18 kV; injection, 12 psi
      x s; capillary and carousel temperature were 20 degrees C. The linear
      relationship was observed between 0.063--2.00 microM using the time-corrected
      peak area ratio of 8-Cl-cAMP to internal standard with correlation coefficient
      greater than 0.99. The intra-day and inter-day coefficients of variation (CV's)
      were less than 12%. The developed method was used for the analysis of plasma
      samples from beagle dogs (n=12) to examine the toxicity of the anticancer drug, 8
      Cl-cAMP, following two, 5-day cycles of continuous intravenous infusion at
      various doses of 8-Cl-cAMP as the sodium salt.

PMID- 11248480
TI  - A preliminary study of beta-cyclodextrin/metoprolol tartrate inclusion complex
      for potential enantiomeric separation.
AB  - The inclusion complex formation between Metoprolol tartarata (MeT) and beta
      cyclodextrin (beta-CD) has been investigated using hyperchromic shift at
      lambda(max) 274.4 nm of MeT. Different parameters such as stirring time, solvent
      composition (aqueous and aqueous/methanol solutions with methanol content up to
      50%), pH values 4.0 and 8.0 were established for optimal inclusion complex
      formation and confirmed two stoichiometric compositions 1:1 and 1:2. Preliminary
      data on usage of MeT/beta-CD complex in reversed-phase HPLC indicate the
      potential application of this complex as a kind of pre-column derivatization for
      enantiomeric separation of beta(1)-blockers.

PMID- 11248479
TI  - Analysis and enantioresolution of donepezil by capillary electrophoresis.
AB  - The analysis of donepezil, a centrally acting acetylcholine esterase inhibitor,
      is described by a CZE method suitable for applications in pharmaceutical field. A
      rapid migration of the analyte was obtained under acidic conditions (pH 3.0);
      with detection wavelength of 320 nm a LOD of 0.8 x 10(-3) mg/ml was provided.
      Applications on real sample (pharmaceuticals) were carried out using two
      different instruments with comparable results in terms of reproducibility and
      accuracy. The use of chiral selectors in the running buffer allowed the
      enantioseparation of donepezil; charged cyclodextrins (carboxymethyl-beta
      cyclodextrin and sulfated-beta-cyclodextrin) were suitable for the chiral
      resolution of the analyte. Interesting results were also obtained using human
      serum albumin. The protein-based CE enantioseparation was carried out at pH 7.4
      avoiding the partial filling technique due to the good absorptivity of donepezil
      at 320 nm. Interestingly, the use of bicine as BGE provided a significative
      improvement in the enantioresolution compared to that obtained by phosphate
      buffer.

PMID- 11248481
TI  - Application of LC-MS analysis to the characterisation of the in vitro and in vivo
      metabolite profiles of RGH-1756 in the rat.
AB  - RGH-1756, 1-(2-methoxy-phenyl)-4-(4-[4-(6-imidazol[2,1-b] thiazolyl)-phenoxy]
      butyl-4-(14)C)-piperazine dimethane is a novel atypical antipsychotic drug
      candidate of Gedeon Richter Ltd. The metabolic pathways of the compound have been
      investigated by profiling the metabolites present in plasma, bile, and faeces
      samples of rats treated with (14)C-RGH-1756. The metabolites formed in vitro by
      rat liver microsomes have also been analysed. Good separation of the compounds
      has been achieved by gradient HPLC method on Zorbax/Bonus RP-C18 column.
      Radiometry and mass spectrometry have been applied to detect and characterise the
      metabolites. The metabolite formed by oxidative cleavage of the chain at the
      carbon atom adjacent to the piperazine nitrogen has been identified as the major
      plasma metabolite. Glucuronide conjugate of hydroxy-RGH-1756 has been found as
      one of the main metabolites excreted in the bile where the unchanged compound has
      not been detected.

PMID- 11248482
TI  - Validation of a chromatographic method to determine E-6006 and its metabolite E
      6332 in rat and dog plasma by solid-phase extraction and capillary gas
      chromatography. Application in pharmacokinetics.
AB  - E-6006, 5-(alpha-[2-(dimethylamino)ethoxy]-2-thienylmethyl)-1-methyl-1H-pyrazole
      is a new antidepressive compound and E-6332, 5-(alpha-[2-(methylamino)ethoxy]-2
      thienylmethyl)-1-methyl-1H-pyrazole is its desmethylate metabolite. With the aim
      of quantifying E-6006 and E-6332, simultaneously in rat or dog plasma, a method
      of analysis based on solid-phase extraction coupled with capillary gas
      chromatographic system with N-P detection was developed and validated. E-6006, E
      6332 and its internal standard (E-4018) were isolated from plasma using an off
      line semiautomatic solid-phase extraction method. Gas chromatography separations
      were carried out by means of 12 m length, 0 2 mm (i.d.) and 0.33 microm (f.t.)
      ULTRA 1 type capillary column in splitless mode of injection at 190 degrees C,
      with a TSD or specific nitrogen--phosphorus detector. No peaks interfering with
      the quantification of E-6332 and E-6006 were observed. The limit of
      quantification was 5 ng/ml with a precision and accuracy <17%. The peak height
      ratios were proportional to E-6332 and E-6006 concentration over the range from 5
      to 600 ng/ml (r(2)>0.998). Mean recoveries of E-6332, E-6006 and internal
      standard from rat plasma were between 57.1 and 82.6. Intra-assay precision
      coefficients were <8.0 and <11.8%, respectively, for E-6332 and E-6006, with an
      accuracy <12.6 and <9.7%. Both inter-assay precision and accuracy were within
      acceptable limits (<15%). In dog, the results were very similar to those obtained
      in rat. To show an example of the suitability of the method to determine E-6332
      and E-6006, plasma profiles obtained after single oral and intravenous
      administration of 20 mg/kg to rats and 25 mg/kg to dogs are reported.

PMID- 11248483
TI  - Development and validation of two chromatographic methods for the quantification
      of E-6087 and one of its metabolites, E-6132, in rat plasma.
AB  - E-6087 is a nonsteroidal anti-inflammatory compound under development that
      selectively inhibits cyclooxygenase-2. In vitro studies have shown that one of
      its metabolites, E-6132, also inhibits this enzyme. Due to chromatographic
      reasons, two reverse phase HPLC methods were developed and validated in order to
      elucidate which compound is responsible for the pharmacological activity in vivo.
      Chromatographic separation of E-6087 was achieved using acetonitrile-phosphate
      buffer (pH 2.5; 25 mM) (60:40, v/v) as mobile phase and two 4.6 x 150 mm x 5
      microm Inertsil ODS-2 columns. For E-6132, two Inertsil ODS-3 columns and 52% of
      acetonitrile were used instead. Internal standards and fluorescence detection
      differed between both methods. The same on-line solid-phase extraction method was
      used. Mean retention times for E-6087 and E-6132 were 15.2 (+/-1.3) and 36.1 (+/
      0.6) min, respectively. The methods were selective and linear over the
      concentration range of 10--500 ng ml(-1) (r(2)>0.996) for E-6087 and 5--200 ng
      ml(-1) (r(2)>0.997) for E-6132. The limits of quantitation were 10 ng ml(-1) (E
      6087) and 5 ng ml(-1) (E-6132) with a precision and accuracy <16% (E-6087) and
      <11% (E-6132). Mean recoveries from plasma were 43.2-61.9% (E-6087) and 60.4-
      65.2% (E-6132). For both compounds, both inter-assay and intra-assay precision
      and accuracy were within acceptable limits (<15%). As an example of the
      suitability of these methods, the results from a pharmacokinetic study are
      reported. After single oral administration of 5 mg kg(-1) of E-6087 to rats,
      plasma concentrations of E-6087 at peak time were higher than those of E-6132,
      suggesting that activity is mainly due to E-6087.

PMID- 11248484
TI  - An HPLC/UV method for the determination of RGH-1756 in dog and rat plasma.
AB  - RGH-1756 (1-(2-methoxy-phenyl)-4-(4-[4-(6-imidazo[2,1-b]-thiazolyl)-phenoxy]
      butyl)-piperazine dimethansulphonate) is a novel atypical antipsychotic candidate
      of Gedeon Richter Ltd. A new HPLC method has been developed and validated for the
      quantitative determination of RGH-1756 in dog and rat plasma. The compound and
      the internal standard are extracted from the biological samples by a simple and
      fast liquid--liquid extraction method, using 1-chlorobutane. The recovery for RGH
      1756 is about 90%. The extracts are analyzed by reversed phase HPLC (column:
      Supelcosil-LC-18-DB 250*4.6 mm, 5 microm, eluent:acetonitrile:methanol:0.2 molar
      ammonium-acetate 40:25:35, lambda=254 nm). The assay is specific for RGH-1756.
      The standard curves are linear in the range between 10 and 2000 ng ml(-1). The
      overall precision (expressed as CV%) and accuracy (expressed as bias%) of quality
      controls and calibration standards are within 15%. The validated lower limit of
      quantification is 10 ng/ml. No indications have been found for possible
      instabilities of RGH-1756 in plasma, in the extraction solvent, or after repeated
      thawing-freezing cycles. The method has been succesfully applied for the
      bioavailability studies of RGH-1756 in the two animal species. In these studies
      results of the inprocess method validation have shown the reliability of the
      method, too. CV% of quality controls in the rat study has been found between 7.4
      and 10.0%, in the dog study between 4.1 and 12.5%. The bias has ranged from 0.4
      to 3.8% and from -4.5 to 1.2% in the rat and dog study, respectively.

PMID- 11248485
TI  - Simultaneous determination of total and free drug plasma concentrations combined
      with batch-wise pH-adjustment for the free concentration determinations.
AB  - Batch-wise pH-adjustment of plasma samples for free concentration determinations
      can be performed directly in the ultrafiltration devices using a CO(2) incubator.
      The pH of the samples could be adjusted to within a sufficiently narrow interval
      though the initial differences in pH were large. The possibilities for
      simultaneous determination of free and total concentrations were studied using
      NAD-299 as a model compound. By adding a known concentration of a (13)C-labelled
      isotope of the studied drug to the sample prior to ultrafiltration it was
      possible to calculate the total concentration from the ratio of the drug peak
      area to the isotope peak area while the free concentration was calculated from
      the drug peak area. Initial experiments showed good precision and accuracy as
      well as a good correlation with concentration data acquired in the conventional
      way.

PMID- 11248487
TI  - High-performance liquid chromatographic determination of ursodeoxycholic acid
      after solid phase extraction of blood serum and detection-oriented
      derivatization.
AB  - Ursodeoxycholic acid (3 alpha,7 beta-dihydroxy-5 beta-cholanoic acid, UDCA) is a
      therapeutically applicable bile acid widely used for the dissolution of
      cholesterol-rich gallstones and in the treatment of chronic liver diseases
      associated with cholestasis. UDCA is more hydrophilic and less toxic than another
      therapeutically valuable bile acid, chenodeoxycholic acid (CDCA), the 7 alpha
      epimer of UDCA. Procedures for sample preparation and HPLC determination of UDCA
      in blood serum were developed and validated. A higher homologue of UDCA
      containing an additional methylene group in the side chain was synthetized and
      used as an internal standard (IS). Serum samples with IS were diluted with a
      buffer (pH=7). The bile acids and IS were captured using solid phase extraction
      (C18 cartridges). The carboxylic group of the analytes was derivatized using 2
      bromo-2'-acetonaphthone (a detection-oriented derivatization), and reaction
      mixtures were analyzed (HPLC with UV 245 nm detection; a 125--4 mm column
      containing Lichrospher 100 C18, 5 microm; mobile phase: acetonitrile--water, 6:4
      (v/v)). Following validation, this method was used for pharmacokinetic studies of
      UDCA in humans.

PMID- 11248488
TI  - Specific and non-specific measurements of tissue angiotensin II cascade members.
AB  - Although angiotensin II (ANG II) has been the focal regulatory peptide of the
      renin-angiotensin system, its proteolytic fragments have recently been
      demonstrated to have biological effects. Conventional measurement of angiotensins
      involves radioimmunoassay (RIA), which is a sensitive binding technique capable
      of measuring low physiological concentrations. However, ANG II antibody cross
      reacts with ANG II and its fragments (ANG II cascade), rendering RIA measurement
      alone to be a non-specific measure of immunoreactive ANG II (ir-ANG II). On the
      other hand, high-performance liquid chromatography (HPLC) is capable of
      separating immunoreactive ANG II cascade members, but may not be sensitive enough
      to detect these low peptide concentrations often present in biological samples.
      Consequently, a reverse-phase HPLC method, with triethylammoniun formate as an
      ion-pair reagent, was developed to separate ANG II and its fragments, ANG III,
      ANG IV and ANG V. This HPLC separation was applied to extracts from normal canine
      hearts and ANG II cascade immunoreactive fractions were collected. Collected
      fractions were quantified by RIA, with the use of separate standard curves. The
      isocratic HPLC separation of ANG II, ANG III, ANG IV and ANG V was achieved in
      less than 5 min with adjacent peaks having baseline resolution. Measured cardiac
      left ventricle ANG III, ANG IV and ANG V concentrations (mean+/-SD) were 5.3+/
      2.2,4.0+/-1.0 and 3.1+/-1.0 fmol/g (n=9), respectively. There was a significant
      difference (P=0.003, n=9) between left ventricular immunoreactive ANG II and
      'true' ANG II, corrected for recovery rates of 86.2+/-22.5 and 53.5+/-16.2
      fmol/g, respectively. We conclude that the combination of HPLC with RIA ensures
      the specific measurement of the ANG II cascade family members while non
      chromatographic processing of tissue renders ANG II measurement non-specific. In
      addition, the use of triethylammonium formate as mobile phase additive is
      superior in the HPLC separation of the angiotensins.

PMID- 11248486
TI  - Determination of myocardial norepinephrine in freely moving rats using in vivo
      microdialysis sampling and liquid chromatography with dual-electrode amperometric
      detection.
AB  - Myocardial norepinephrine (NE) is considered a meaningful parameter for
      estimation of cardiac function. Long lasting changes in myocardial NE appear to
      be not only a consequence of pathologic processes in the myocardium, but may be a
      factor responsible for some diseases (e.g. increased propensity for arrhythmias
      or negative effect on left ventricular contractility in congestive heart
      failure). In this respect monitoring of myocardial NE is of great importance. A
      microdialysis sampling technique coupled with liquid chromatography with
      electrochemical detection (LCEC) was developed to measure the in vivo NE
      concentration in the myocardial interstitium of conscious, freely moving rats.
      LCEC using a dual-electrode amperometric detection in the series configuration
      provided detection limits for NE of 10 pg/ml in 20 microl microdialysis samples.
      Microdialysis probes of the linear design were implanted in the myocardial tissue
      in the periphery of the left descending coronary artery. The basal steady-state
      concentration of NE in myocardial dialysate of awake, freely moving rats was
      found to be 0.17+/-0.026 ng/ml. Delivery through the microdialysis probe of the
      NE reuptake inhibitor desipramine (DMI) at a concentration of 0.1 mM increased NE
      release to 153+/-13% of control. If the concentration of DMI in the perfusate was
      increased to 1.0 mM, NE release increased to only 166+/-21% of control.

PMID- 11248489
TI  - Stability-indicating HPLC assay and solution stability of a new diaziridinyl
      benzoquinone.
AB  - RH1, 3-methyl-6-hydroxymethyl-2,5-diaziridinyl-1,4-benzoquinone, is a NQO1
      (NAD(P)H quinone oxidoreductase) directed anti-tumor agent. It is designed as a
      water soluble analog of MeDZQ (3,6-dimethyl-2,5-diaziridinyl-1,4-benzoquinone)
      and is a drug candidate for clinical evaluation. A HPLC assay has been developed
      for its analysis. The assay is sensitive (ldl<0.2 ng), precise (rsd<1%), linear
      (r(2)=0.9997), accurate (error<0.6%), and stability-indicating. Using the
      developed assay, aqueous stability of RH1 has been evaluated. Both aziridine
      rings in MeDZQ are known to be easily hydrolyzable in aqueous solutions, however,
      hydrolysis of the second aziridine ring in RH1 appears inhibited.

PMID- 11248490
TI  - The unusual gradient elution for reversed phase HPLC of a strong chelator as an
      active drug substance.
AB  - The new approach to drug development, especially for cardiovascular and brain
      diseases, brought to synthesis of new lipophillic derivatives of strong calcium
      chelator BAPTA - DP-b99 and DP-109. Due to their chelating ability, these
      compounds require metal-free stationary phases, and their high hydrophobicity
      resulted in unusually steep gradient elution. Novel HPLC methods for analysis of
      these two compounds were developed. Purospher RP-C18, 5 microm, 125 x 3.0 mm and
      XTerra RP18, 3.5 microm, 100 x 4.6 mm columns with a steep gradient from: 1%
      acetic acid to acetonitrile were used for DP-b99, and Hypersil HyPurity C4, 5
      microm, 100 x 4.6 mm column with a steep gradient from 1% Acetic acid to 5% THF
      in methanol -- for DP-109. Versatile detection techniques could be used with
      these LC procedures. The methods appeared to be sensitive, selective,
      reproducible and stability indicating. They could be easily upgraded to
      bioanalytical methods with LC-MS technique.

PMID- 11248491
TI  - Optimization of HPLC method for stability testing of bacitracin.
AB  - A stability indicating HPLC assay for bacitracin has been developed and
      validated. The assay is based on a gradient elution, reversed phase column and UV
      diode array detection. On the basis of our previous analytical work several
      additional systematic HPLC tests for optimization of analytical method were
      performed. In order to achieve the highest selectivity of HPLC method, tests were
      conducted with extremely complex samples -- zinc bacitracin feed grade as food
      additive for animals. The influence of pH of mobile phase and type of columns on
      chromatographic separation of active (A, B(1) and B(2)) and inactive (F)
      polypeptide components of bacitracin were investigated in detail. It was found
      also that the peak B(1) comprises three and the peak F two subunits -- probably
      isomers. The obtained analytical procedure proved to be very selective and
      effective for the simultaneous determination of active polypeptide A, B(1) and
      B(2), impurities, known and unknown degradation products and ballast material.

PMID- 11248492
TI  - HPLC and GC-MS screening of Chinese proprietary medicine for undeclared
      therapeutic substances.
AB  - Traditional Chinese medicine includes raw medicinal materials and Chinese
      proprietary medicine (CPM). Despite being of natural origin, toxic effects,
      adulteration with synthetic therapeutic substances and even deaths had been
      associated with CPM. There is thus a need to develop analytical technique to
      rapidly screen for undeclared toxic and therapeutic substances in CPM. In this
      study, a high performance liquid chromatography-diode-array detection method was
      developed and used to screen for undeclared therapeutic substances in CPM. An
      ultraviolet (UV) library of 266 drugs had been compiled. Solute identification
      was performed by comparing the analytical data (UV spectra, retention time and
      relative retention time) with those of the 266 standards. Gas chromatography-mass
      spectrometry was used as a confirmation method. These chromatographic methods had
      been shown to be selective and reproducible in screening for undeclared drugs in
      CPM. Using the method developed, 41 CPM samples in seven categories were screened
      for undeclared therapeutic substances. One anti-asthmatic CPM was found to
      contain codeine.

PMID- 11248493
TI  - Simultaneous HPLC determination of nitrendipine and impurities of the process of
      synthesis.
AB  - A method has been developed for separation of nitrendipine and its impurities of
      reaction partners and side reaction products by high-performance liquid
      chromatographic method on a RP-18 column and detection at 238 nm. The mobile
      phase composition that provided an acceptable nitrendipine resolution, in large
      excess and possible impurities, in a short elution time, is methanol:water
      (70:30) and pH 3. Linearity (r> or =0.999), reproducibility (RSD=0.8--1.4%),
      determination limit (0.5--2%) and recovery (99.8--102.3) were validated and found
      to be satisfactory. This method enables monitoring of the process of synthesis,
      as well as the choice of the synthetic design.

PMID- 11248494
TI  - Validated HPLC method for quantifying permethrin in pharmaceutical formulations.
AB  - An isocratic HPLC method for permethrin determination in raw material and
      pharmaceutical presentations as lotion and shampoo has been developed and
      validated following ICH recommendations. Cis and trans- isomers, impurities and
      degradation products are well separated. The chromatographic analysis were
      performed on a 4 microm particle C-18 Nova-Pak (Waters, Madrid, Spain) column (15
      x 0.39 cm) kept in a Biorad column oven at 35 degrees C. Mobile phase consisted
      of methanol--water (78:22, v/v) at a flow rate of 1 ml/min. UV detection was
      performed at 272 nm and peaks were identified with retention times as compared
      with standards and confirmed with characteristic spectra using the photodiode
      array detector.

PMID- 11248495
TI  - Validation of an HPLC method for the quantification of ambroxol hydrochloride and
      benzoic acid in a syrup as pharmaceutical form stress test for stability
      evaluation.
AB  - A method is described for ambroxol, trans-4-(2-amino-3,5-dibromobenzylamino)
      cyclohexanol hydrochloride, and benzoic acid separation by HPLC with UV detection
      at 247 nm in a syrup as pharmaceutical presentation. Optimal conditions were:
      Column Symmetry Shield RPC8, 5 microm 250 x 4.6 mm, and methanol/(H(3)PO(4) 8.5
      mM/triethylamine pH=2.8) 40:60 v/v. Validation was performed using standards and
      the pharmaceutical preparation which contains the compounds described above.
      Results from both standards and samples show suitable validation parameters. The
      pharmaceutical grade substances were tested by factors that could influence the
      chemical stability. These reaction mixtures were analysed to evaluate the
      capability of the method to separate degradation products. Degradation products
      did not interfere with the determination of the substances tested by the assay.

PMID- 11248496
TI  - Ion exchange chromatographic determination of olpadronate, phosphate, phosphite,
      chloride and methanesulfonic acid.
AB  - A method based on single column ion chromatography with UV detection was
      developed for purity testing and assay of monosodium olpadronate. The analyte
      aqueous solution is precipitated with methanol to enhance the
      impurities/olpadronate molar ratio, thus improving purity determination at trace
      levels. The resulting solution is injected into a standard chromatographic system
      with UV detector in indirect mode with a Waters IC Pak HR column using diluted
      nitric acid as the mobile phase. The method was fully validated according to ICH
      guidelines for the determination of phosphite, phosphate, chloride and
      methanesulfonic acid in olpadronate being suitable for purity testing and assay.

PMID- 11248497
TI  - The use of a response surface methodology on HPLC analysis of methyldopa,
      amiloride and hydrochlorothiazide in tablets.
AB  - A multifactor optimisation technique is successfully applied to develop a new
      HPLC method in which methyldopa, hydrochlorothiazide and amiloride were analysed
      and determined on a C18 column with detection at 286 nm. The optimal conditions
      of HPLC separation were determined with the aid of the response surface diagram -
      'window diagram'. The effect of simultaneously varying the pH, proportion
      aqueous acetic acidum and methanol in the mobile phase were studied to optimise
      the separation. The mobile phase composition that provides an acceptable
      resolution methyldopa, hydrochlorothiazide and amiloride in a short elution time
      is water--methanol (75:25) and pH 3.60. The k' values for methyldopa,
      hydrochlorothiazide and amiloride after optimisation were 1.40, 2.50 and 5.33,
      respectively. Relative retention (alpha) for ratio hydrochlorothiazide/methyldopa
      and amiloride/hydrochlorothiazide were 1.767 and 2.159, respectively. Correlation
      coefficients of the calibration curves for all analytes were greater than 0.995
      and the R.S.D. values for the slope and the intercept with respect to the
      linearity were less than 2%. A method is applied for the quantitative analysis of
      Alatan tablets (Lek-Ljubljana). The powdered tablets are extracted with methanol,
      containing caffeine as the internal standard and assayed by comparison of peak
      areas after liquid chromatography. The high recovery (for all analytes about
      100%) and the low R.S.D. (<2%) confirm good precision and reproducibility of the
      chromatographic method.

PMID- 11248498
TI  - Potentiometric determination of acetylsalicylic acid by sequential injection
      analysis (SIA) using a tubular salicylate-selective electrode.
AB  - This paper deals with the development of an automated procedure for formulation
      assays and dissolution tests based on a sequential injection analysis (SIA)
      system involving an ion-selective electrode as sensing device. Construction of a
      tubular salicylate (Sal) selective electrode suitable for potentiometric
      determination of acetylsalicylic acid (Asa) in pharmaceutical formulations is
      described. The flow-through electrode is formed by a PVC membrane containing
      29.2% (w/w) PVC, 5.8% (w/w) tetraoctylammonium salicylate (ionic sensor), 58.5% o
      nitrophenyloctylether (plasticizer) and 6.5% (w/w) p-tert-octylphenol
      (stabilising additive which increases electrode selectivity). The calibration
      range is 0.05--10 mM Sal, the limit of detection (LOD) is 0.05 mM Sal, the slope
      is 56.0 mV per decade at 22 degrees C. The R.S.D. is 0.20% (15 readings) when
      determining 2.5 mM Sal in standard solution. The electrode is used for sensing
      Asa after its on-line chemical hydrolysis to Sal in a SIA system. The sampling
      rate is 6 h(-1) but for the dissolution tests the frequency is increased to 20 h(
      1). The SIA set-up is employed for the assay of Asa in plain tablets, composed
      tablets and effervescent tablets and for performing dissolution tests of normal
      and sustained release tablets. Results obtained by this technique compare well
      with those required by the US Pharmacopoeia XXIV.

PMID- 11248499
TI  - Modeling of supercritical extraction of mannitol from plane tree leaf.
AB  - The objective of this study was to investigate the theoretical feasibility of
      using supercritical fluid extraction of Mannitol from plane tree leaf as an
      alternative technology in the pharmaceutical industry. Simulation of an
      extraction column using dense liquid and supercritical carbon dioxide was modeled
      involving partial differential equations, using orthogonal collocation on finite
      elements. The important solvent extraction parameters such as the partition
      coefficient, mass transfer coefficient, dispersion coefficient, molecular
      diffusion and extraction efficiency (the amount of Mannitol extracted versus the
      amount of solvent used) were investigated as a function of the dimensionless
      Reynold's and Peclet numbers in order to optimize the extraction column geometry
      and the carbon dioxide operating conditions. The results of this study
      demonstrated that supercritical extraction is a viable technique for Mannitol
      production and that the process conditions for a large commercial extraction
      system do not require a high temperature in order to obtain a high extraction
      efficiency. However, at low pressures, the solubility of Mannitol in carbon
      dioxide would limit the success of the extraction process and at very high
      pressures the extraction technique may not be economically feasible. To
      investigate the authenticity of the mathematical model, the experimental data for
      the desorption of hexachlorobenzene from soil was compared with the theoretical
      results of this research. The model is able to predict the experimental data
      quite well without any adjustable parameters.

PMID- 11248500
TI  - Simultaneous determination of quercetin, kaempferol and (E)-cinnamic acid in
      vegetative organs of Schisandra chinensis Baill. by HPLC.
AB  - A reversed-phase high-performance liquid chromatographic (RP-HPLC) separation
      method with UV spectrophotometric detection has been developed for the
      determination of major components in leaves and caulomas of Schisandra chinensis
      Baill. The flavonols (quercetin and kaempferol) and (E)-cinnamic acid were
      analysed after extraction with alcohol from the dry plant material.
      Identification was based on retention times and UV spectra by comparison with
      commercial standards. Quercetin, kaempferol and (E)-cinnamic acid were separated
      within 12 min using acetonitrile-aqueous 0.05% ortho-phosphoric acid (40:60 v/v)
      mobile phase. The method has been successfully applied for the quantitative
      analysis of all three major components in several samples from different harvests
      using propylparaben as the internal standard.

PMID- 11248501
TI  - Evaluation of radical scavenging properties of several plants, fresh or from a
      herbalist's, using a superoxide dismutase biosensor.
AB  - The experimental evaluation of properties of defence against free radicals
      represents an extremely interesting heuristic and applicational objective.
      Research was carried out to experimentally evaluate the scavenging properties of
      several fruits and plants, fresh or from a herbalist's using an amperometric
      superoxide dismutase (SOD) biosensor recently developed by the present authors.
      The superoxide radical was produced in solution using the xanthine/xanthine
      oxidase system; measurements were carried out by comparing biosensor response to
      superoxide radical both in the presence and absence of the sample considered.

PMID- 11248502
TI  - Application of conventional UV, photodiode array (PDA) and fluorescence (FL)
      detection to analysis of phenolic acids in plant material and pharmaceutical
      preparations.
AB  - Free phenolic acids (PhAs) contained in methanolic extracts of Eleutherococcus
      senticosus roots and pharmaceutical preparations, deriving from this plant, were
      isolated by solid-phase extraction (SPE) and identified by reversed-phase high
      performance liquid chromatography (RP-HPLC). To obtain precise, accurate and
      validated results of qualitative and quantitative analysis, ultraviolet (at
      lambda=254 nm), photodiode array (at lambda=254 and 280 nm) and fluorescence (at
      lambda(Ex)=230 or 265 nm and lambda(Em)=350 nm) detection was used. Additionally,
      the HPLC separation of PhAs on two different octadecyl sorbents: Hypersil
      (Shandon, UK) and Symmetry (Waters, USA) was performed. Eight PhAs: chlorogenic,
      protocatechuic, p-hydroxybenzoic, caffeic, vanillic, syringic, p-coumaric and
      ferulic, in different quantitative proportions, were identified, both in the
      roots of E. senticosus and pharmaceutical formulations examined.

PMID- 11248503
TI  - In vitro study on the transfer of volatile oil components.
AB  - The following volatile oils were tested in vitro: chamomile (Matricaria recutica
      L.), peppermint (Mentha piperita L.) and sage (Salvia officinalis L.) to obtain
      information on which components of volatile oils or minerals are able to pass
      through the membranes under different conditions. The transfer of chamomile and
      peppermint oil from aqueous volatile oil to the stomach (pH=1.1) and then to the
      plasma (pH=7.5) was studied, and the transfer of sage oil through the skin (from
      pH=5.5 to pH=7.5) was examined. The transfer of some components was more
      favorable than that of others. The transfer of chamomile oil was faster to buffer
      pH=1.1 than from buffer pH=1.1 to buffer pH=7.5 and most of the components,
      except for chamazulene, passed through the membranes. In the case of peppermint
      the components went through the membranes in the first 15 min although the main
      components mostly remained in the initial solution. The sage oil transferred
      showed the same characteristics as the starting oil. A small amount of metal
      present in the volatile oils also passed through the membranes. The transfer of
      metals varied, depending on the time, type of the oil, metal quality and the
      conditions applied.

PMID- 11248504
TI  - Application of f--f luminescence of terbium ion for determination of non
      steroidal anti-inflammatory drug-niflumic acid.
AB  - A simple, rapid and sensitive luminescence method for determination of niflumic
      acid (NFA) is described. The method is based on the intramolecular energy
      transfer from niflumic acid to terbium ion (Tb(3+)) in the presence of
      trioctylphosphine oxide (TOPO). Optimum conditions for the formation of the NFA
      Tb(3+)-TOPO ternary complex have been investigated. The calibration graph is
      linear over the range 0.002--0.02 microg ml(-1). The relative standard deviation
      is close to 4%. The recoveries obtained by applying the method to the analysis of
      urine ranged from 94--102%.

PMID- 11248505
TI  - Evaluation of electrophoretic method versus chromatographic, potentiometric and
      absorptiometric methodologies for determing pK(a) values of quinolones in
      hydroorganic mixtures.
AB  - The advantages of using capillary electrophoresis (CE) over other methodologies
      for determining pK(a) values of drugs in hydroorganic media are discussed. The
      focus of the discussion based upon the pK(a) values of a series of quinolones
      determined in acetonitrile (MeCN)--water mixtures by CE, liquid chromatography,
      potentiometric, and spectrophotometric methods.

PMID- 11248506
TI  - Analysis of all-in-one parenteral nutrition admixtures by liquid chromatography
      and laser diffraction: study of stability.
AB  - All-in-one parenteral nutrition admixtures are complex lipid emulsions
      (oil/water) which require absolute sterility, stability and no precipitates.
      Particle diameter must be in the range 0.4--1 microm in order to mime the size of
      chylomicra. Added vitamins must not degrade during infusion time (24 h). In this
      study, the physicochemical stability of parenteral nutrition admixtures was
      tested in the course of time at different storage temperatures. Two liquid
      chromatographic methods, based on solid phase extraction (SPE), were developed
      for fat-soluble vitamin determination. Stability studies were carried out on
      three industrial lipid emulsions and on six compounded all-in-one admixtures.
      They were stored at three different temperatures: 4 degrees C (storage), 25
      degrees C (compounding) and 37 degrees C (infusion); then they were analyzed at
      starting time and at 24, 48 and 72 h after compounding. Particle diameter was
      determined by means of Laser Particle Sizer Analysette 22, which uses laser
      diffraction technique (light scattering -- reverse Fourier optics). Fat-soluble
      vitamins (retinol palmitate and alpha-, delta-, gamma-tocopherol) were determined
      in admixtures with a branded vitamin compound called Idroplurivit Liofilizzato.
      Samples were extracted by SPE on C(18) cartridges, then they were separated by
      reversed-phase liquid chromatography (LC) and detected by ultraviolet detection
      (retinol palmitate) and electrochemical detection (tocopherols). Laser
      diffraction analysis pointed out that particle size did not change in the course
      of time at the tested temperatures. LC analysis showed that vitamins interact
      each other and degrade after compounding at different times and storage
      temperatures; only retinol palmitate is stable at 37 degrees C. Retinol palmitate
      recovery was 98%, coefficient of variation (CV) 5.4%, detection limit 25
      microg/l, limit of quantitation 75 microg/l and there were not interfering
      substances. Tocopherols average recovery was 99%, CV 3.5%, detection limit 15
      ng/l and limit of quantitation 50 ng/l. In conclusion, all-in-one parenteral
      admixtures were proved to be physically stable under analysis conditions, but
      degradation of retinol palmitate and tocopherols requires admixtures with
      vitamins to be infused within 24 h after compounding.

PMID- 11248507
TI  - Thermal stability of disodium and calcium phosphomycin and the effects of the
      excipients evaluated by thermal analysis.
AB  - In the present study, Thermogravimetry (TG) and Differential Scanning Calorimetry
      (DSC) are simultaneously applied to determine the thermal properties of two
      antibiotic salts, disodium and calcium phosphomycin, used either pure or in
      association with several excipients. This study was carried out kinetically as
      well by mathematical elaboration of the TG curves performed according to an
      isothermal procedure applied at different fixed temperatures. Kinetic parameters
      showing agreement with those produced by the isothermal method were also obtained
      by means of a non-isothermal method using a dynamic TG curve alone. The main aims
      of the work were to provide reliable kinetic parameters (kinetic constant k,
      activation energy E(a) and pre-exponential factor A) to evaluate the thermal
      stability of phosphomycin salts in the presence and absence of the excipients
      generally contained in the phosphomycin-based pharmaceutical forms available on
      the market, and to obtain information concerning compatibility towards the active
      components. These kinetic parameters were then used to extrapolate shelf-life and
      half-life values at room temperature for pure active components in the solid
      state and for their pharmaceutical derivatives.

PMID- 11248508
TI  - Doping control for nandrolone using hair analysis.
AB  - A sensitive, specific and reproducible method for the quantitative determination
      of nandrolone in human hair has been developed. The sample preparation involved a
      decontamination step of the hair with methylene chloride. The hair sample (about
      100 mg) was solubilized in 1 ml NaOH IN, 15 min at 95 degrees C, in presence of
      10 ng nandrolone-d(3) used as an internal standard. The homogenate was
      neutralized and extracted using consecutively a solid phase (Isolute C18) and a
      liquid--liquid (pentane) extraction. The residue was derivatized by adding 50
      microl MSTFA/NH4I/2-mercaptoethanol (1000:2:5; v/v/v), then incubated for 20 min
      at 60 degrees C. A 4-microl aliquot of the derivatized extract was injected into
      the column (HP5-MS capillary column, 5% phenyl--95% methylsiloxane, 30 m x 0.25
      mm i.d. x 0.25 mm film thickness) of a Hewlett Packard (Palo Alto, CA) gas
      chromatograph (6890 Series) via a Hewlett Packard (7673) autosampler. The assay
      was capable of detecting 0.5 pg of nandrolone per mg of hair when approximately
      100 mg of hair were processed. Linearity was observed for nandrolone
      concentrations ranging from 1 to 50 pg/mg with a correlation coefficient of
      0.997. Intra-day and between-day precisions at 10 pg/mg were 11.2 and 15.1%,
      respectively, with an extraction recovery of 81.7%. The analysis of three strands
      of hair, obtained from three bodybuilders, revealed the presence of nandrolone at
      the concentration of 1, 3.5 and 7.5 pg/mg.

PMID- 11248509
TI  - Determination of the adenosine A(1) agonist N(6)-cyclopentyladenosine in rat
      blood by solid-phase extraction and HPLC.
AB  - A solid-phase extraction procedure has been developed for the isolation of the
      adenosine A1 receptor agonist N(6)-cyclopentyladenosine from rat blood. The
      biological samples were spiked with N(6)-cyclopentyladenosine and the analogue
      N(6)-cyclohexladenosine (internal standard), diluted with sodium hydroxide,
      loaded onto disposable cartridges with subsequent desorption with methanol and
      analysis by HPLC. The performance of columns pre-packed with different C18-bonded
      silica phases or with a polymeric reversed-phase sorbent (Oasis HLB) was
      assessed. The highest extraction efficiencies (recovery rates>83.3%) for the two
      N6-alkyl substituted adenosines were achieved by the Oasis HLB cartridges. In
      addition, the polymeric sorbent provided reproducible recoveries (relative
      standard deviation<4.8%), whereas large variations (relative standard deviation
      values, 9--16.3%) in the extraction yields were observed using the conventional
      silica-based C18 cartridges. The described sample preparation method is rapid,
      simple, selective and it is suitable for pharmacokinetic studies.

PMID- 11248510
TI  - A new HPLC micromethod to measure total plasma homocysteine in newborn.
AB  - Total plasma homocysteine (tHcy) in children may be an useful biochemical marker
      for genetic risk of premature cardiovascular disease. We reported a rapid,
      isocratic HPLC method able to process very small amount of newborn plasma
      samples. A blood sample from heel capillary circulation was collected, using a
      heparinized capillary glass tube. Plasma sample from 1 to 10 microl was
      derivatized with ammonium-7-fluorobenzo-2-oxa-1,3-diazole-4-sulphonate after
      reduction with tri-n-butylphosphine and analyzed on Discovery C18 column, with a
      solution of acetonitrile-dihydrogenphosphate 0.1 M (8:92 v/v pH*2.1). This assay
      ensures a good recovery (95%), precision (CV 4.5%) and linearity (y=2.41x + 0.31,
      r=1). Due to its simplicity and reliability, our method is suitable for routine
      analysis of tHcy and other aminothiols (Cys, Cys-Gly, GSH) assessed for clinical
      and research purposes. With this HPLC method we have assayed tHcy levels in 1400
      apparently healthy newborn babies (tHcy mean value=4.9+/-2.7 microM). In
      conclusion, this accurate and linear HPLC method allows measurement of tHcy in
      newborn during the routinary capillary blood collection in the fourth living day
      without any other invasive procedure.

PMID- 11248511
TI  - HPLC determination of adenosine in human synovial fluid.
AB  - A high-performance liquid chromatographic method has been developed for the
      quantitative determination of adenosine in human synovial fluid. The method is
      simple, rapid and, overall, selective. No interference with the components of the
      biological matrix was observed in these chromatographic conditions. An ODS (250 x
      4.6 mm) 5 microm column was used with an isocratic elution of a phosphate buffer
      acetonitrile mobile phase. Detection was carried out on a UV detector at 260 nm.
      Calibration curve was found to be linear in the 0.7--70 microg ml(-1) range.
      Linear regression analysis of the data demonstrates the efficacy of the method in
      terms of precision and accuracy. The precision of this method, calculated as the
      relative standard deviation (RSD) of the recoveries (1.57--2.21%), was excellent.
      The limits of quantitation (LOQ) and detection (LOD) were respectively 0.7 and
      0.2 microg ml(-1). The method was applied to some samples of synovial effusion
      from patients affected by rheumatoid arthritis. The concentrations of adenosine
      which were found were included in the range of the calibration curve.

PMID- 11248512
TI  - Enzymatic determination of acetylcarnitine for diagnostic applications.
AB  - An enzymatic method was proposed for determination of acetylcarnitine (AcCar),
      even when carnitine (Car), non-acetylated form, co-exists. The method is
      consisted of four enzymatic reactions: First, AcCar is hydrolysed by
      acylcarnitine hydrolase to yield acetate; followed by the other three reactions
      coupled with three enzymes, respectively, acetate kinase, pyruvate kinase and
      lactate dehydrogenase; finally, the acetate formation causes a decrease in NADH.
      The amount of AcCar is then evaluated as the change in absorbance at 340 nm. The
      reagent composition of the reaction mixture was determined, and the
      characteristics of the method were investigated. The dilution test showed a good
      linearity over a wide range. The precision and accuracy tests produced
      satisfactory results. The co-existence of Car gave no effect on the measurement.
      The present method was found to be used easily, simply and rapidly for the
      selective determination of AcCar.

PMID- 11248513
TI  - Determination of enzyme (angiotensin convertase) inhibitors based on enzymatic
      reaction followed by HPLC.
AB  - For determination of levels of plasmatic inhibitor of ACE (angiotensin
      convertase) a simple method was used based on a combination of enzymatic reaction
      followed by an HPLC determination of its product. The inhibitor (e.g.
      enalaprilat) was at first separated from the biological material by
      deproteination (methanol). Then, an aliquot of the sample was added to the
      reaction mixture containing a commercial ACE enzyme, its specific substrate FAPGG
      (N-(3-[2-furyl]acryloyl)-Phe-Gly-Gly) and buffer (Tris--HCl, pH 7.5). Degree of
      inhibition of the conversion of this substrate to FAP (desGlyGlyFAPGG) by the
      inhibitor present in the sample is related to its amount by a simple dose
      response relationship. The amount of the FAP was determined by an HPLC on a RP-18
      column with an acetonitril--nonylamine buffer (pH 2.4, adjusted with phosphoric
      acid) as a mobile phase with detection at 305 nm. Alternatively, the activity of
      the endogenous ACE present in the plasma was measured. The substrate FAPGG was
      added to the plasmatic sample containing both the inhibitor and endogenous ACE
      (as the sample was not deproteinized in this case) and the reaction product was
      determined as above. Inhibitor concentration has been obtained from a dose-
      response curve expressing the interaction with inhibitor with an ACE enzyme.

PMID- 11248514
TI  - Bioanalysis of age-related changes of lipid metabolism in nonagenarians.
AB  - The aim of the present study was the bioanalysis of lipid metabolism in the aged
      patients and to study the relationship between these biochemical markers and
      longevity. Eleven nonagenarians, nine women and two men, aged 94+/-3 years and
      ten control patients, six women and four men, aged 84+/-5 years, followed at the
      Department of Metabolic Care and Gerontology, Charles University, Teaching
      Hospital entered the study. All subjects were self-sufficient, without major
      illnesses and free living. At the start of the project the free fatty acids
      (FFA), thiobarbituric reactive substances (TBARS), retinol, alpha tocopherol,
      ascorbic acid, cholesterol, triacylglycerols, phospholipids in serum, in
      lipoprotein fractions and fatty acids (FA) and phospholipids in erythrocyte
      membrane were determined. We used capillary gas chromatography for determination
      of fatty acids. Retinol and alpha tocopherol were analysed by reversed-phase high
      performance liquid chromatography, other parameters were determined
      spectrophotometrically or spectrofluorometrically. We found significantly higher
      LDL polyunsaturated fatty acids (PUFA) 22:4n--3 (P=0.028) and 22:6n--3 (P=0.018)
      and a significant increase of HDL alpha tocopherol/cholesterol ratio (P=0.034) in
      nonagenarians. There were not any significant differences in erythrocyte membrane
      fatty acids and phospholipids. In serum we found significantly higher level of
      TBARS (3.22+/-1.22 vs 1.98+/-0.71 micromol/l, P=0.012) in nonagenarians, other
      parameters were not changed significantly. The higher concentration of PUFAs in
      LDL and alpha tocopherol in HDL might be parameters related to longevity.

PMID- 11248515
TI  - Essential oils analysis. II. Mass spectra identification of terpene and
      phenylpropane derivatives.
AB  - Mass spectra are widely used in order to identify the peaks resulting from a
      chromatographic separation. The most common approach to solve the problem for
      unknowns on whom very little other structural information is available is the use
      of a retrieval algorithm and a reference mass spectra database. The wide variety
      of mass spectra recorded with different instruments under various experimental
      conditions can lead to erroneous results. In order to improve the accuracy of the
      results, we proposed earlier an identification algorithm, which combines the
      information obtained from both GC and MS fingerprints. This paper presents a new
      algorithm based on the comparison of the unknown mass spectra with several
      libraries (including Wiley and NIST) by using reverse and direct search
      algorithms respectively. The results of the comparisons were quantified with
      respect to the match quality and the interference compounds. A global match index
      for the comparison using all the above information was computed and the results
      were presented as the match probability. This index expresses more accurately the
      matches between unknown and all the available libraries mass spectra. In order to
      verify our algorithm, we tried to identify the compounds separated by GC-MSD from
      different species of Acorus calamus L. (Araceae) essential oils. The probability
      of the matches increases compared with the quality of matches resulting from
      Wiley and NIST libraries.

PMID- 11248516
TI  - Quantitative analysis of analgoantipyretics in dosage form using planar
      chromatography.
AB  - In the therapy of pain of weaker genesis, frequently used drugs usually represent
      a mix of analgoantipyretics of different chemical structures, mostly derivatives
      of salicylic acid, pyrazolone and p-aminophenol as well as derivatives of
      propionic and acetylsalicylic acid. For the determination of these drugs,
      different chromatographic methods have been applied, mostly HPLC, due to the the
      lower polarity (pyrazolones derivatives) and thermolability, as well as
      nonvolatility of compounds investigated. TLC method, considering advantages which
      include simplicity, reasonable sensitivity, rapidity, excellent resolving power
      and low cost has been successfully explored for the determination of
      analgoantipyretic compounds. The aim of this work was to develop a simple and
      rapid HPTLC method for the determination of acetylsalicylic acid, paracetamol,
      caffeine and phenobarbitone in dosage form. The determination of
      analgoantipyretics were performed on pre-coated HPTLC silica gel plates (10 x 20
      cm(2)) by development in the mobile phase dichlormethane-ethyl acetate
      cyclohexane-isopropanol-0.1 M HCL-formic acid (9:8:3:1.5:0.2:0.2 v/v/v/v/v/v).
      Migration distances (68.6+0.2 mm, 54.1+0.1 mm, 36.4+0.14 mm and 85.9+0.11 mm for
      acetylsalicylic acid, paracetamol, caffeine and phenobarbitone, respectively)
      with low RSD values (0.13--0.39%) showed a satisfactory reproductivity of the
      chromatographic system. TLC scanner was used for direct evaluation of the
      chromatograms in the reflectance/absorbance mode. Established calibration curves
      (r>0.999), precision (0.3--1.02%) and detection limits, as well as recovery
      values (96.51--98.1%) were validated and found to be satisfactory. The method was
      found to be reproducible and convenient for the quantitative analysis of
      compounds investigated in their dosage forms.

PMID- 11248517
TI  - Direct voltammetry for vitamin B(2) determination in aqueous solution by using
      glassy carbon electrode.

PMID- 11248518
TI  - Vibrio parahaemolyticus associated with cholera-like diarrhea among patients in
      North Jakarta, Indonesia.
AB  - A diarrhea study was conducted in North Jakarta, Indonesia from December 1996
      through December 1997. Vibrio parahaemolyticus was isolated from 333 (6.1%) of
      5442 rectal swab samples collected from patients with cholera-like diarrhea.
      Vibrio cholerae O1 was isolated from 545 (10.0%) and V. cholerae non-O1 from 183
      samples (3.4%), respectively. Patients positive for V. parahaemolyticus were
      mostly adults between 20 and 40 years of age, with males constituting 62%. A
      majority (65%) of these patients demonstrated watery diarrhea with a frequency of
      fewer than 10 episodes per 24 hour. A large number of the patients had abdominal
      pain (83%) and vomiting (76%) and were non-febrile (90%). The highest isolation
      rate (9.6%) of V. parahaemolyticus was found during the dry season (June, July)
      and the lowest (4.5%) in the rainy season (December, January, February). All of
      the V. parahaemolyticus isolates were hemolytic on human blood agar (positive
      Kanagawa) but none was urease positive. Disk diffusion antibiotic susceptibility
      tests performed on the isolates demonstrated resistance to ampicillin (98%),
      cephalothin (24%), kanamycin (15%), colistin (97%), neomycin (2%) and ceftriaxone
      (0.3%). All isolates (100%) were sensitive to chloramphenicol, tetracycline,
      trimethoprim-sulfamethoxazole, gentamicin, and ciprofloxacin.

PMID- 11248519
TI  - Rapid identification of pathogenic bacteria by single-enzyme amplified fragment
      length polymorphism analysis.
AB  - Despite major progress in their treatment and prevention, bacterial infections
      remain a significant cause of morbidity and mortality worldwide. In responding to
      a disease outbreak, rapid and accurate identification of the bacterial species
      involved is of paramount importance. Strain level discrimination is desirable to
      allow selection of treatment modalities, and in the case of a deliberate release,
      for identification of the source. Single-enzyme amplified fragment length
      polymorphism (SE-AFLP) analysis was used to perform species and strain
      identification of subgroup I Bacilli, Yersinia, Staphylococci and Escherichia
      coli. By careful selection of AFLP primers, it was possible to obtain
      reproducible and sensitive identification to strain level, even within the highly
      monomorphic species Bacillus anthracis. SE-AFLP fragments can be analyzed using
      standard gel electrophoresis, and can be easily scored by visual inspection, due
      to the low complexity of the fingerprint obtained by this method. These features
      make SE-AFLP suitable for use in either field or laboratory applications.

PMID- 11248520
TI  - Identification by 16S ribosomal RNA gene sequencing of an Enterobacteriaceae
      species with ambiguous biochemical profile from a renal transplant recipient.
AB  - Traditional ways of identification of bacteria by phenotypic characteristics
      cannot be used for non-cultivable organisms and organisms with unusual
      biochemical profiles. In this study, an Enterobacteriaceae was isolated in pure
      growth from the mid-stream urine of a 67-year old renal transplant recipient with
      urinary tract infection. Conventional biochemical tests did not reveal a pattern
      resembling any known member of the Enterobacteriaceae family. The Vitek system
      (GNI+) showed that it was 18% Leclercia adecarboxylata and 55% Klebsiella
      ozaenae; whereas the API system (20E) showed that it was 99.8% Rahnella
      aquatilis. 16S ribosomal RNA gene sequencing showed that there was 7 base
      differences between the isolate and Enterobacter cloacae, 18 base differences
      between the isolate and Enterobacter asburiae, 17 base differences between the
      isolate and Enterobacter cancerogenus, 35 base differences between the isolate
      and K. ozaenae, 27 base differences between the isolate and L. adecarboxylata,
      and 72 base differences between the isolate and R. aquatilis, indicating that the
      isolate most closely resembled a strain of E. cloacae. Identification of the
      organism in this study is important, as the choice of antibiotics would be
      radically different. In this case, cephalosporins should be avoided regardless of
      in-vitro susceptibility as cephalosporins are well-known to select for AmpC
      derepressed mutants in Enterobacter, and previous administration of third
      generation cephalosporins is more likely to be associated with multidrug
      resistant Enterobacter isolates than is administration of antibiotics that do not
      include a third-generation cephalosporin.

PMID- 11248521
TI  - On-site diagnosis of H. pylori infection by urine.
AB  - We have recently developed an on-site diagnostic kit for H. pylori infection
      using urine (utilizing immunochromatographic method employing a nitrocellulose
      membrane coated by extracted H. pylori antigen). Accordingly, we investigated its
      usefulness in 155 consecutive dyspeptic patients using the 13C urea breath test
      as a gold standard and further compared its performance with two commercially
      available rapid diagnostic kits that use whole blood (Helisal Rapid Blood, and
      ImmunoCard H. pylori). As the results, the urine based on-site diagnostic kit
      provided 95.9% sensitivity and 87.9% specificity with 92.9% accuracy, which were
      comparable or even better than that of both rapid whole blood tests, suggesting
      its usefulness in screening of H. pylori infection.

PMID- 11248522
TI  - The interaction of human monocytes, monocyte-derived macrophages, and
      polymorphonuclear neutrophils with caspofungin (MK-0991), an echinocandin, for
      antifungal activity against Aspergillus fumigatus.
AB  - The collaboration between human effector cells and caspofungin (MK-0991), a 1,3
      beta-D glucan synthase inhibitor, was studied for antifungal activity against
      Aspergillus fumigatus. Caspofungin was co-cultured for 24h with either human
      monocytes (Monos), monocyte-derived macrophages (MDM), or polymorphonuclear
      neutrophils (PMN) against germlings of A. fumigatus and antifungal activity
      assessed using the XTT metabolic assay. Caspofungin at 0.1 micorg/ml and 0.05
      microg/ml or Monos alone against germlings caused significant inhibition.
      Microscopically this was correlated with less growth and stunted malformed
      hyphae. The addition of caspofungin at 0.1 microg/ml and 0.05 microg/ml to the
      monocyte cultures increased antifungal activity. The inhibition of the
      combination was significantly greater than drug alone (P <.01) and Monos alone (P
      <.01). MDM against Aspergillus germlings inhibited hyphal growth. The combination
      of caspofungin at 0.1 microg/ml and 0.05 microg/ml to the macrophage cultures
      increased antifungal activity. The growth inhibition by the combination was
      significantly greater than drug alone (P <.01) and MDM alone (P <.01). There was
      no significant interference with or enhancement of PMNs and caspofungin. These
      data support the activity of caspofungin against A. fumigatus in vitro, and
      indicates a cooperative activity with human effector cells. This suggests
      caspofungin in vivo would have increased efficacy as it combines with host
      defenses against A. fumigatus.

PMID- 11248523
TI  - Antibacterial activity of 41 antimicrobials tested against over 2773 bacterial
      isolates from hospitalized patients with pneumonia: I--results from the SENTRY
      Antimicrobial Surveillance Program (North America, 1998).
AB  - Pneumonia is the second most frequent cause of nosocomial infection, and
      hospitalization frequently is needed for community-acquired pneumonia. Knowledge
      of causative pathogens through periodic surveillance, and their prevailing
      antimicrobial susceptibility patterns becomes paramount in choosing appropriate
      empiric therapy. The SENTRY Antimicrobial Surveillance Program, tracks pathogen
      distribution worldwide since 1997 and documents emerging resistance to a wide
      range of antimicrobial agents. During the respiratory disease season in 1998,
      each of 30 medical centers (25 in the United States [US], and five in Canada
      [CAN]) contributed 100 consecutive isolates obtained from hospitalized patients
      with suspected pneumonia. The 2773 organisms, processed by the monitor consisted
      of a total of 35 species, with Staphylococcus aureus comprising 25.6% of all
      isolates and five other species (Pseudomonas aeruginosa 18.7%, Haemophilus
      influenzae 9.4%, Streptococcus pneumoniae 7.8%, Klebsiella spp. 7.0%, and
      Enterobacter spp. 6.7%) making up almost 50% of the total. In the US, pneumococci
      (8.5%) were more prevalent than in CAN (4.1%; p = 0.001). The US isolates of S.
      pneumoniae were variably susceptible to penicillin (76.8%), with non-susceptible
      strains demonstrating greater levels of cross resistance to macrolides (31.8%),
      cefepime (9.0%) and cefotaxime (6.8%), but remaining susceptible to gatifloxacin
      and quinupristin/dalfopristin. H. influenzae and Moraxella catarrhalis were
      generally ampicillin-resistant, 40.4-44.4% and 93.7-95.7%, respectively. P.
      aeruginosa remained very susceptible to amikacin (91.3-93.8%) > tobramycin >
      meropenem > piperacillin/tazobactam > gentamicin > piperacillin > cefepime (80.0
      81.8%). Extended spectrum beta-lactamase phenotypes among the Klebsiella spp.
      were isolated from five medical centers in the US and were 4.8-6.0% overall; a
      rate similar to the previous year. Among the US isolates of Enterobacter spp.,
      only 77.6% and 79.6% were susceptible to ceftazidime and cefotaxime,
      respectively, but >90% were inhibited by cefepime, imipenem, meropenem,
      aminoglycosides, and fluoroquinolones. Isolates from CAN were generally more
      susceptible, except for Pseudomonas isolates, where resistance to
      aminoglycosides, fluoroquinolones and imipenem was greater. The SENTRY Program
      results outline important national differences in the frequencies of pathogen
      occurrence, but more importantly, identify unstable patterns of resistance to
      available antimicrobial drugs, and serves as a reference for results of other
      local, national or international investigations.

PMID- 11248524
TI  - Evaluation of two rapid modifications of the 4-nitrophenyl-beta-D
      glucopyranosiduronic acid (PGUA) assay for the identification of Escherichia coli
      from urine.
AB  - Two rapid modifications of a tube assay for the detection of beta-glucuronidase
      activity (PGUA assay) were evaluated for the identification of Escherichia coli
      from urine cultures. A microwell and filter paper adaptation of the PGUA assay
      were tested using 1,234 oxidase-negative, Gram-negative rods isolated from urine
      on MacConkey agar in clinically significant numbers. There was perfect
      correlation between both methods and 676 of 797 E. coli isolates were PGUA
      positive within 2 h while all of remaining isolates were PGUA-negative
      (sensitivity = 85%; specificity = 100%). We conclude that either modified format
      of the PGUA assay provides a useful, inexpensive, and rapid alternative spot test
      for the definitive identification of E. coli from urine because of the high
      degree of specificity.

PMID- 11248525
TI  - Effect of pre-stain viability on the acid-fast staining characteristics of
      Mycobacterium species.
AB  - Five species of mycobacteria were stained by Ziehl-Neelsen, Kinyoun and Auramine
      Rhodamine after either routine autoclaving, or exposure to rifabutin and
      ciprofloxacin. Organisms from each treatment group were stained and compared to
      viable controls. ATCC strains and fresh clinical isolates of all five species
      were evaluated. All species in both treatment protocols presented similar
      staining characteristics. Viability of mycobacteria, therefore, must be
      established by culture.

PMID- 11248526
TI  - Carbapenem-resistant Serratia marcescens isolates producing Bush group 2f beta
      lactamase (SME-1) in the United States: results from the MYSTIC Programme.
AB  - Two carbapenem (imipenem, meropenem)-resistant Serratia marcescens strains were
      isolated in the United States (Chicago, IL) through the 1999 MYSTIC (Meropenem
      Yearly Susceptibility Test Information Collection) Programme. The S. marcescens
      antimicrobial susceptible patterns were: susceptible to ceftriaxone, ceftazidime,
      and cefepime (MICs, < or = 0.25 microg/ml), and resistance to the carbapenems
      (imipenem and meropenem; MIC, > 32 microg/ml) and aztreonam (MIC, > = 16
      microg/ml). Each S. marcescens isolate shared an identical epidemiologic type
      (ribotype and PFGE) and the outer membrane protein profile was also identical to
      those of the wild type susceptible strains from the same medical center. The PCR
      utilizing bla(sme-1) primers amplified a gene product that was identified as
      consistent with SME-1 after DNA sequencing. Imipenem and meropenem resistance due
      to production of carbapenem-hydrolyzing enzymes among clinical isolates is still
      very rare, but microbiology laboratories should be aware of these chromosomally
      encoded enzymes among class C beta-lactamases producing enteric bacilli such as
      S. marcescens and Enterobacter cloacae.

PMID- 11248527
TI  - Three independent yearly analyses of the spectrum and potency of metronidazole: a
      multicenter study of 1,108 contemporary anaerobic clinical isolates.
AB  - To comply with ongoing United States Food and Drug Administration (FDA)
      recommendations about the validation of prescribing information, in each of three
      years (1994, 1996, 1997) at six medical centers, metronidazole was tested against
      > or = 50 strains of a range of contemporary anaerobic clinical bacteria. Species
      having > or = 90% susceptibility (MIC, < or = 8 microg/ml) to metronidazole
      (fulfilling FDA requirements) included Bacteroides fragilis, B. distasonis, B.
      ovatus, B. thetaiotaomicron, B. vulgatus, Fusobacterium spp. and Clostridium spp.
      Only Eubacterium spp. and anaerobic Gram-negative cocci failed to achieve the
      required proportion of susceptibility throughout the 3 year period. Metronidazole
      appears to remain highly active versus anaerobic species associated with strict
      anaerobic organisms.

PMID- 11248528
TI  - Activity and spectrum of BMS 284756, a new des-F (6) quinolone, tested against
      strains of ciprofloxacin-resistant Gram-positive cocci.
AB  - BMS 284756, a novel des-fluoroquinolone with an expanded potency versus Gram
      positive pathogens, demonstrated potent activity against a wide range of 3,541
      ciprofloxacin-resistant (MIC, > or = 2 microg/ml) Gram-positive cocci. These
      strains were selected from more than 24,000 isolates gathered as part of the 1999
      SENTRY Antimicrobial Surveillance Program. Further clinical development appears
      warranted.

PMID- 11248529
TI  - Synergistic effect of gentamicin plus ampicillin on enterococci.

PMID- 11248530
TI  - Glioneuronal tumors and medically intractable epilepsy: a clinical study with
      long-term follow-up of seizure outcome after surgery.
AB  - The present study intends to identify factors that predict postoperative clinical
      outcome in patients with gangliogliomas (GG) and dysembryoplastic neuroepithelial
      tumors (DNT). We evaluated the medical records of 45 patients with GG and 13
      patients with DNT, treated surgically between 1985 and 1995. We assessed several
      clinical and histopathological features and analyzed the data statistically. At 5
      years postoperatively, 63% of patients with GG and 58% of patients with DNT were
      seizure-free (Engel's class I). Younger age at surgery (P<0.01 for GG and P<0.05
      for DNT), total resection (P<0.01 for GG), shorter duration of epilepsy (P<0.01),
      absence of generalized seizures (P<0.01 for GG; P<0.05 for DNT) and absence of
      epileptiform discharge in the post-operative EEG (P<0.01 for GG; P=0.01 for DNT)
      predicted a better postoperative seizure outcome. Tumor recurrence with malignant
      progression occurred in eight histologically benign GG and two anaplastic GG and
      was associated which older age at surgery (P=0.01) and subtotal resection of the
      tumor (P<0.01). Our results indicate that a prompt diagnosis, relatively soon
      after seizure onset, followed by complete resection of glioneuronal tumors
      provides the best chance for curing epilepsy and preventing their malignant
      transformation.

PMID- 11248531
TI  - Evaluation of the accuracy of seizure descriptions by the relatives of patients
      with epilepsy.
AB  - The descriptions of seizures by witnesses are important in the diagnosis and
      classification of epileptic seizures. The aim of the study was to evaluate the
      accuracy of this information obtained from relatives of patients with epileptic
      and non-epileptic attacks. Thirty patients with epileptic or non-epileptic
      attacks had seizures videorecorded whilst inpatients at the Assessment and
      Treatment Centre of the National Society for Epilepsy and the National Hospital
      for Neurology and Neurosurgery, Chalfont, Buckinghamshire, UK. A relative or
      close friend of each patient viewed the recording and subsequently completed a
      structured questionnaire, testing recall of 15 separate elements of the episode.
      This account was compared to a definitive evaluation completed by medical staff.
      An accuracy of describing seizures was therefore obtained. Our results showed
      that there was a wide variation in the accuracy of recall with convulsive
      episodes described less well than non-convulsive (median accuracies 44.5 and 70%,
      respectively, P<0.05). Attacks in which the diagnosis had been changed, following
      admission, from the one obtained on history alone were particularly inaccurately
      described (median accuracy 26%). Elements of the questionnaire that were most
      inaccurately recalled were description of limb movement and post-ictal behaviour.
      Those most accurately described were facial appearance and vocalization. Features
      only present in non-epileptic attacks included reactivity to eyelash stimulation,
      opisthotonic posturing, flailing or protective limb movements. In conclusion, our
      results confirm that inaccuracy exists when witnesses describe attacks and that
      this may lead to errors in diagnosis and subsequent treatment.

PMID- 11248532
TI  - Lack of aura experience correlates with bitemporal dysfunction in mesial temporal
      lobe epilepsy.
AB  - The diagnostic value of lack of aura experience in patients with temporal lobe
      epilepsy (TLE) is unclear. PURPOSE: To evaluate possible factors of bitemporal
      dysfunction in patients with mesial TLE who did not experience an aura in
      electroencephalography EEG/video monitoring for epilepsy surgery. METHODS: Ictal
      scalp EEG propagation patterns of 347 seizures of 58 patients with mesial
      temporal lobe sclerosis or non-lesional mesial TLE, interictal epileptiform
      discharges (IED), presence of unilateral mesial temporal lobe sclerosis in visual
      magnetic resonance imaging (MRI) analysis, prose memory performance, history or
      not of an aura, and postictal memory or absence of an aura were analyzed. The
      ictal EEG was categorized as follows. EEG seizure: (a) remaining regionalized,
      (b) non-lateralized, (c) showing later switch of lateralization or bitemporal
      asynchronous ictal patterns. RESULTS: Absent aura in monitoring was significantly
      correlated with absence of unitemporal MRI sclerosis (P=0.004), bitemporal IED
      (P=0.008), and propagation of the ictal EEG to the contralateral temporal lobe
      (P=0.001). Other historical data and interictal prose memory performance were not
      significantly correlated with absent aura. Ten of 11 patients without aura in
      monitoring also had absent or rare auras in their history. CONCLUSIONS: Lack of
      aura experience strongly correlates with indicators of bitemporal dysfunction
      such as bitemporal interictal sharp waves and bitemporal ictal propagation in
      scalp EEG, and absence of lateralized MRI sclerosis in patients with mesial TLE.
      The fact that absent auras are not correlated with episodic memory suggests a
      transient memory deficit, probably because of rapid propagation to the
      contralateral mesial temporal lobe.

PMID- 11248533
TI  - Epilepsy-induced decrease of L-type Ca2+ channel activity and coordinate
      regulation of subunit mRNA in single neurons of rat hippocampal 'zipper' slices.
AB  - L-type voltage-sensitive Ca2+ channels (VSCCs) preferentially modulate several
      neuronal processes that are thought to be important in epileptogenesis, including
      the slow afterhyperpolarization (AHP), LTP, and trophic factor gene expression.
      However, little is yet known about the roles of L-type VSCCs in the epileptogenic
      process. Here, we used cell-attached patch recording techniques and single cell
      mRNA analyses to study L-type VSCCs in CA1 neurons from partially dissociated
      (zipper) hippocampal slices from entorhinally-kindled rats. L-type Ca2+-channel
      activity was reduced by >50% at 1.5-3 months after kindling. Following recording,
      the same single neurons were extracted and collected for mRNA analysis using a
      recently developed method that does not amputate major dendritic processes.
      Therefore, neurons contained essentially full complements of mRNA. For each
      collected neuron, mRNA contents for the L-type pore-forming alpha1D/Ca(v)1.3
      subunit and for calmodulin were then analyzed by semiquantitative kinetic RT-PCR.
      L-type alpha1D-subunit mRNA was correlated with L-type Ca2+-channel activity
      across single cells, whereas calmodulin mRNA was not. Thus, these results appear
      to provide the first direct evidence at the single channel and gene expression
      levels that chronic expression of an identified Ca2+-channel type is modulated by
      epileptiform activity. Moreover, the present data suggest the hypothesis that
      down regulation of alpha1D-gene expression by kindling may contribute to the long
      term maintenance of epileptiform activity, possibly through reduced Ca2+
      dependent AHP and/or altered expression of other relevant genes.

PMID- 11248534
TI  - The A-B neuropsychological assessment schedule (ABNAS): the further refinement of
      a patient-based scale of patient-perceived cognitive functioning.
AB  - PURPOSE: To provide further evidence of the reliability and validity of the ABNAS
      as a measure of patient-perceived cognitive side effects of antiepileptic drug
      treatment. METHODS: The measure was developed specifically to assess patient
      perceived cognitive side effects of antiepileptic drug treatment. Evidence of its
      reliability and validity has been previously documented and this evidence has
      been further extended by administration of a battery of 400 questionnaires to two
      groups (200 people with epilepsy, PWE; and 200 controls who do not have
      epilepsy). The questionnaire packs consisted of the ABNAS, HADS, the everyday
      memory questionnaire, and the Adverse Events Profile. Data were analysed using
      MAP-R and SPSS. RESULTS: Further evidence of the psychometric properties of the
      scale demonstrated that it had excellent reliability (Cronbach's alpha=0.96) and
      good face, congruent, content and construct validity. The sensitivity of the
      instrument was demonstrated through analysis of floor and ceiling levels.
      CONCLUSIONS: The ABNAS is a reliable, tool for the detection of cognitive
      impairments associated with epilepsy and its treatment. We have provided further
      evidence of its criterion validity. This measure has the potential to be a useful
      tool for both clinical practice and clinical trials.

PMID- 11248535
TI  - The effects of gabapentin on different ligand- and voltage-gated currents in
      isolated cortical neurons.
AB  - A clear picture of the mechanisms of action of the anti-epileptic agent
      gabapentin is far from being accomplished. We have analyzed the effects of
      gabapentin on ligand- and voltage-gated currents in isolated adult rat cortical
      neurons. Gabapentin failed to modify glutamate currents and produced a slight
      reduction of GABA responses. Negligible inhibition of sodium, but consistent
      inhibition of high-voltage-activated calcium conductance was promoted by
      gabapentin. In addition, gabapentin reduced calcium current sensitivity to
      dihydropyridine agonist and antagonists. Interestingly, gabapentin also decreased
      a not-inactivating, cadmium-sensitive, potassium current. These unconventional
      effects might underlie its efficacy in a variety of diseases which involve
      periodic discharge patterns as neuropathic pain or essential tremor.

PMID- 11248536
TI  - Expression of an embryonic intermediate filament protein in amygdaloid kindled
      rats.
AB  - Amygdaloid kindling is well known as an experimental model of temporal lobe
      epilepsy. However, the mechanism of kindling epileptogenesis remains unclear. To
      examine the remodelling process in kindling, we performed immunohistochemistry of
      nestin, an embryonic intermediate neurofilament protein, in amygdaloid kindled
      rats. In rats expressing focal seizures (kindling stage C3), nestin
      immunoreactive cells (NIC) were detected at ipsilateral piriform cortex (PC) and
      ipsilateral perirhinal cortex (PRh), and at PC bilaterally in fully kindled rats
      expressing secondary generalized seizures (kindling stage C5). Double staining
      with glial fibrillary acidic protein revealed that almost all reactive astrocytes
      at PC express nestin immunoreactivity. These results suggest that glial NIC may
      participate in the remodelling process at the PC and PRh areas. This is the first
      report of nestin expression in kindling and suggests that glial nestin at PC and
      PRh may play a significant role in permanent epileptogenesis in kindling.

PMID- 11248537
TI  - Topiramate in refractory partial-onset seizures in children, adolescents and
      young adults: a multicentric open trial.
AB  - PURPOSE: This study was to evaluate the efficacy and safety of topiramate (TPM)
      in refractory partial epilepsy in children, adolescents and young adults.
      METHODS: We performed a prospective open label add-on study in 55 patients (age 2
      30 years, mean 15 years) with refractory partial seizures. Topiramate was added
      to one or two other baseline drugs and the efficacy was rated according to
      seizure type and frequency. RESULTS: TPM was initiated at a daily dose of 0.5-1
      mg/kg, followed by a 2-week titration at increments of 1-3 mg/kg/24h, up to a
      maximum daily dose of 12 mg/kg. After 9 months of treatment, 11 patients (20%)
      had 100% fewer seizures and 25 patients (45%) had a more than 50% seizure
      reduction. TPM appeared to be effective both in cryptogenic (76.2%) and
      symptomatic (58.8%) partial epilepsies. Mild to moderate adverse events were
      present in 25 patients (45.4%), mostly represented by drowsiness, nervousness and
      hyporexia with or without weight loss. CONCLUSION: TPM was an overall effective
      and safe add-on drug both in cryptogenic and symptomatic childhood refractory
      partial seizures, the adverse reactions being generally mild or moderate.

PMID- 11248538
TI  - Neuroimaging abnormalities in children with an apparent first unprovoked seizure.
AB  - OBJECTIVE: To determine the incidence and type of neuroimaging abnormalities in
      children presenting with a first seizure. METHODS: In a prospective observational
      study, 411 children with a first afebrile seizure were seen between 1983 and
      1992. Imaging studies were performed in 218 (53%). For this analysis we examined
      the most sensitive neuroimaging study performed which included 159 computed
      tomography scans and 59 magnetic resonance imagings (MRI). RESULTS: Four children
      were found to have lesions requiring intervention (brain tumor in two,
      neurocysticercosis in two). The remaining 407 were enrolled in a follow-up study
      of children with a first unprovoked seizure. After a mean follow-up of >10 years,
      none have developed clinical evidence of a tumor. In these 411 children, 45 (21%)
      of 218 imaging studies were abnormal. The most common abnormalities were focal
      encephalomalacia (n=16) and cerebral dysgenesis (n=11). Although children with
      partial seizures were more likely to be imaged (64%) than children with
      generalized seizures (43%) (P<0.001), the fraction of abnormal imaging studies
      was similar in both groups. Six children with a normal neurological examination
      who were initially classified as cryptogenic were subsequently found to have
      errors of cerebral migration on MRI. The incidence of lesions requiring acute
      intervention in children presenting with a first seizure is low. A significant
      proportion will have neuroimaging abnormalities particularly on MRI. CONCLUSIONS:
      Neuroimaging should be considered in any child with a first seizure who does not
      have an idiopathic form of epilepsy.

PMID- 11248539
TI  - 2-deoxyglucose enhances epileptic tolerance evoked by transient incomplete brain
      ischemia in mice.
AB  - The aim of the study was to assess the influence of chronic treatment with a non
      metabolisable glucose analogue, 2-deoxyglucose (2-DG) at a 150 mg/kg dose on long
      term epileptic tolerance (ET) evoked by 30 min bilateral carotid artery clamping
      (BCCA) in mice. The effects of protein synthesis inhibition with cycloheximide
      (CHX), given in three daily doses of 2.5 mg/kg starting either 1 day before (peri
      insult regimen) or 1 day after the priming insult (post-insult regimen), on ET
      development was also studied. Seizures were induced 14 days after BCCA with 3.5
      mg/kg of bicuculline; this dose (CD97) evokes convulsions in 97% of normal
      untreated mice. BCCA resulted in decreased mortality, prolonged latency to the
      onset of generalised convulsions and decreased overall seizure score. CHX given
      in the post-insult regimen did not influence, while the peri-insult regimen
      abolished, all signs of BCCA-evoked ET. 2-DG treatment of sham-operated animals
      resulted in a moderate but significant decrease in mortality rate and a tendency
      toward a lower seizure score. BCCA combined with 2-DG treatment resulted in a
      marked decrease in mortality rate, as well as reduction in all indicators of
      seizure susceptibility. CHX abolished the antiepileptic effects of BCCA alone, as
      well as BCCA combined with 2-DG, while it did not influence the 2-DG-related
      decrease in mortality. We conclude that the development of BCCA-induced epileptic
      tolerance, as well as unmasking antiepileptic effects of 2-DG by BCCA, is
      dependent on protein synthesis.

PMID- 11248542
TI  - Cell regulation. Web alert.

PMID- 11248544
TI  - Localization and modulation of ErbB receptor tyrosine kinases.
AB  - The ErbB family of receptor tyrosine kinases serves as a model for understanding
      the propagation of growth factor signals across the plasma membrane and the
      interpretation of those signals into a cellular response. Recent studies point to
      a critical role for the accumulation of ErbBs at specific cell-surface locations
      in the fidelity of ErbB signaling. The past year has witnessed significant
      advances in our understanding of the molecular mechanisms of ErbB localization
      and the role of PDZ-domain-containing proteins and cell-surface glycoproteins in
      directly modulating signaling through ErbBs.

PMID- 11248545
TI  - Phosphoserine/threonine-binding domains.
AB  - Phosphorylation of proteins on serine and threonine residues has traditionally
      been viewed as a means to allosterically regulate catalytic activity. Research
      within the past five years, however, has revealed that serine/threonine
      phosphorylation can also directly result in the formation of multimolecular
      signaling complexes through specific interactions between phosphoserine/threonine
      (pSer/Thr)-binding modules and phosphorylated sequence motifs. pSer/Thr-binding
      proteins and domains currently include 14-3-3, WW domains, forkhead-associated
      domains, and, tentatively, WD40 repeats and leucine-rich regions. It seems likely
      that additional modules will be found in the future. The amino acid sequences
      recognized by these pSer/Thr-binding modules show partial overlap with the
      optimal phosphorylation motifs for different protein kinase subfamilies, allowing
      the formation of specific signaling complexes to be controlled through
      combinatorial interactions between particular upstream kinases and a particular
      binding module. The structural basis for pSer/Thr binding differs dramatically
      between 14-3-3 proteins, WW domains and forkhead-associated domains, suggesting
      that their pSer/Thr binding function was acquired through convergent evolution.

PMID- 11248546
TI  - Expanding roles for beta-arrestins as scaffolds and adapters in GPCR signaling
      and trafficking.
AB  - beta-arrestins play previously unsuspected and important roles as adapters and
      scaffolds that localize signaling proteins to ligand-activated G-protein-coupled
      receptors. As with the paradigmatic role of the beta-arrestins in uncoupling
      receptors from G proteins (desensitization), these novel functions involve the
      interaction of beta-arrestin with phosphorylated heptahelical receptors. beta
      arrestins interact with at least two main classes of signaling proteins. First,
      interaction with molecules such as clathrin, AP-2 and NSF directs the clathrin
      mediated internalization of G-protein-coupled receptors. Second, interaction with
      molecules such as Src, Raf, Erk, ASK1 and JNK3 appears to regulate several
      pathways that result in the activation of MAP kinases. These recent discoveries
      indicate that the beta-arrestins play widespread roles as scaffolds and/or
      adapter molecules that organize a variety of complex signaling pathways emanating
      from heptahelical receptors. It is likely that additional roles for the beta
      arrestins remain to be discovered.

PMID- 11248547
TI  - Subcellular targeting by membrane lipids.
AB  - The reversible localization of signaling proteins to both the plasma and the
      internal membranes of cells is critical for the selective activation of
      downstream functions and depends on interactions with both proteins and membrane
      lipids. New structural and biochemical analyses of C1, C2, PH, FYVE, FERM and
      other domains have led to an unprecedented amount of information on the molecular
      interactions of these signaling proteins with regulatory lipids. A wave of
      studies using GFP-tagged membrane binding domains as reporters has led to new
      quantitative insights into the kinetics of these signaling mechanisms.

PMID- 11248548
TI  - Multiple roles for Cdc42 in cell regulation.
AB  - The Rho family member Cdc42 can signal through a number of cellular pathways
      fundamental to growth, differentiation and apoptosis. Recently, information has
      come at an impressive pace, both with regard to previously identified targets for
      Cdc42 that regulate the actin cytoskeleton (e.g. WASP) and cellular stress
      pathways (e.g. PAK) and with regard to newly identified targets such as the
      coatomer protein complex and PAR6. Recent results hint at a previously
      unappreciated link between these various cellular processes.

PMID- 11248549
TI  - Regulating cellular actin assembly.
AB  - Cellular actin assembly is tightly regulated. The study of pathogen motility has
      led to the identification of several cellular factors that are critical for
      controlling this process. Pathogens such as Listeria require Ena/VASP and Arp2/3
      proteins to translate actin polymerization into movement. Recent work has
      extended these observations and uncovered some similarities and surprising
      differences in the way cells and pathogens utilize the actin cytoskeleton.

PMID- 11248550
TI  - HIF-1 and mechanisms of hypoxia sensing.
AB  - Hypoxia-inducible factor 1 (HIF-1) is an oxygen-regulated transcriptional
      activator that plays essential roles in mammalian development, physiology and
      disease pathogenesis. The HIF-1 alpha subunit is subjected to oxygen-dependent
      ubiquitination and proteasomal degradation that is mediated by the von Hippel
      Lindau protein. Interaction of HIF-1 alpha transactivation domains with
      coactivators is induced by hypoxia. The signal transduction pathway remains
      enigmatic, but involves generation of reactive oxygen species. Nitric oxide
      induces HIF-1 alpha under non-hypoxic conditions but inhibits hypoxia-induced HIF
      1 alpha expression.

PMID- 11248551
TI  - PTEN and myotubularin phosphoinositide phosphatases: bringing bioinformatics to
      the lab bench.
AB  - Phosphoinositides play an integral role in a diverse array of cellular signaling
      processes. Although considerable effort has been directed toward characterizing
      the kinases that produce inositol lipid second messengers, the study of
      phosphatases that oppose these kinases remains limited. Current research is
      focused on the identification of novel lipid phosphatases such as PTEN and
      myotubularin, their physiologic substrates, signaling pathways and links to human
      diseases. The use of bioinformatics in conjunction with genetic analyses in model
      organisms will be essential in elucidating the roles of these enzymes in
      regulating phosphoinositide-mediated cellular signaling.

PMID- 11248552
TI  - Combinatorial control of the specificity of protein tyrosine phosphatases.
AB  - Protein tyrosine phosphatases (PTPs), the enzymes that dephosphorylate tyrosyl
      phosphoproteins, were initially believed to be few in number and serve a
      'housekeeping' role in signal transduction. Recent work indicates that this is
      totally incorrect. Instead, PTPs comprise a large superfamily whose members play
      critical roles in a wide variety of cellular processes. Moreover, PTPs exhibit
      exquisite substrate specificity in vivo. Recent evidence has led us to propose
      that members of the PTP family achieve selectivity through different combinations
      of specific targeting strategies and intrinsic catalytic domain specificity.

PMID- 11248553
TI  - Excitatory Eph receptors and adhesive ephrin ligands.
AB  - Ephrins are cell surface associated ligands for Eph receptor tyrosine kinases and
      are implicated in repulsive axon guidance, cell migration, topographic mapping
      and angiogenesis. During the past year, Eph receptors have been shown to
      associate with glutamate receptors in excitatory neurons, suggesting a role in
      synapse formation or function. Moreover, ephrin/Eph signaling appears to regulate
      neural stem cell proliferation and migration in adult mouse brains. The mode of
      action of ephrin/Ephs has been expanded from repulsion to adhesion and from cell
      surface attachment to regulated cleavage.

PMID- 11248554
TI  - Development of the limb neuromuscular system.
AB  - Appendages, such as wings of a fly or limbs of a vertebrate, are excellent models
      to study the principles of patterning and morphogenesis. In the adult these
      structures are used for a variety of behaviors, including locomotion. Although
      support structures of the adult vertebrate limb are generated within the limb
      bud, its dynamic elements are derived from the somitic mesoderm and neural tube.
      Recent studies show that regional patterns set up in the mesenchyme-filled limb
      bud guide muscle precursors and developing motor axons to their proper location
      within the limb. Subsequent development of the neuromuscular system is regulated
      by cell surface interactions between pre-specified muscle fibers and motor axons.

PMID- 11248555
TI  - The Stat family in cytokine signaling.
AB  - During the past few years studies from several laboratories have utilized gene
      disruption approaches to define the function of members of the Stat family of
      transcription factors. The results have demonstrated that each family member has
      unique, critical, non-redundant functions in signal transduction through members
      of the cytokine receptor superfamily. Many of the family members mediate
      functions associated with innate or acquired immunity. With the availability of
      mice deficient in one or more of the Stats, critical experiments are possible to
      evaluate the roles of Stat signal transduction pathways in cellular
      transformation as well as evaluating their specific roles in a range of cellular
      responses to cytokines.

PMID- 11248556
TI  - HATs on and beyond chromatin.
AB  - The role of histone acetylation as a key mechanism of transcriptional regulation
      has been well established. Recent advances suggest that histone
      acetyltransferases also play important roles in histone-modulated processes such
      as DNA replication, recombination and repair. In addition, acetylation of
      transcriptional cofactors and other proteins is an efficient means of regulating
      a diverse range of molecular interactions. As new histone acetyltransferases and
      substrates are rapidly emerging, it is becoming apparent that protein acetylation
      may rival phosphorylation as a mechanism to transduce cellular regulatory
      signals.

PMID- 11248557
TI  - DNA-PK, ATM and ATR as sensors of DNA damage: variations on a theme?
AB  - The DNA damage signalling pathway is a core element of the cellular response to
      genotoxic insult, and its components play key roles in defending against
      neoplastic transformation. Recent work has indicated that the human ATM and ATR
      proteins, and their yeast homologues, are intimately involved in sensing DNA
      damage, suggesting parallels with the DNA double-strand break repair enzyme DNA
      PK.

PMID- 11248558
TI  - Enzymatic activities of Sir2 and chromatin silencing.
AB  - Heritable domains of generalized repression are a common feature of eukaryotic
      chromosomes and involve the assembly of DNA into a silenced chromatin structure.
      Sir2, a conserved protein required for silencing in yeast, has recently been
      shown to couple histone deacetylation to cleavage of a high-energy bond in
      nicotinamide adenine dinucleotide (NAD) and the synthesis of a novel product, O
      acetyl-ADP-ribose. The deacetylase activity provides a direct link between Sir2
      and the hypoacetylated state of silent chromatin. However, the unusual coupling
      of deacetylation to cleavage and synthesis of other bonds raises the possibility
      that deacetylation is not the only crucial function of Sir2.

PMID- 11248560
TI  - Gene silencing by double-stranded RNA.
AB  - Eukaryotes silence gene expression in the presence of double-stranded RNA
      homologous to the silenced gene. Silencing occurs by the targeted degradation of
      mRNA. Biochemical reactions that recapitulate this phenomenon generate RNA
      fragments of 21--23 nucleotides from the double-stranded RNA. These stably
      associate with an RNA endonuclease and probably serve as a discriminator to
      select mRNAs. Once selected, mRNAs are cleaved at sites 21--23 nucleotides apart.
      This mechanism, termed RNAi, has functional links to viral defense and silencing
      phenomena, such as cosuppression. It also functions to repress the hopping of
      transposable elements.

PMID- 11248559
TI  - Transcriptional regulation in lymphocytes.
AB  - Lymphocytes have been used to investigate many cellular processes, including
      lineage commitment, differentiation, proliferation and apoptosis. The
      transcription factors that mediate these processes are often expressed broadly in
      many cell types. The emerging theme is one of cell-type-specific regulation,
      affecting not only the functional activation of transcription factors but also
      their access to appropriate regions of DNA.

PMID- 11248562
TI  - Long-term results of non-operative treatment of anterior cruciate ligament
      injury.
AB  - We retrospectively reviewed the record of 89 patients with complete anterior
      cruciate ligament injury, documented by arthroscopic examination to investigate
      the long-term results in relation to the generation of osteoarthritis. The mean
      age of the patients was 34.9 years at follow-up and the mean duration of follow
      up was 12.0 years. The mean Lysholm score was 89 points at follow-up. The mean
      Tegner activity score was 5.7 points before injury and 4.5 points at follow-up.
      Plain radiographs revealed 63% of osteoarthritis and 37% of which had joint space
      narrowing. The age of the patients, the level of sports activity, the history of
      meniscectomy, obesity and the osteoarthritis of the contralateral knee were found
      to be significant risk factors in osteoarthritis after anterior cruciate ligament
      injury. The most influential factor for osteoarthritis was considered
      meniscectomy, in combination with the risk factors of primary osteoarthritis. It
      should also be noted that modification of sports activity level was the most
      important factor for avoiding the combined injury of meniscus and osteoarthritis.

PMID- 11248561
TI  - The anterior cruciate ligament--current concepts.

PMID- 11248563
TI  - Anterior cruciate ligament rupture: reconstruction surgery and rehabilitation. A
      nation-wide survey of current practice.
AB  - A database of the current practice of anterior cruciate ligament (ACL)
      reconstruction surgery in Great Britain was collated from a postal survey. This
      survey revealed that clear trends are emerging in the United Kingdom (UK) with
      regard to ACL reconstruction surgery (such as the type of graft used and timing
      of surgery) and rehabilitation. Certain issues, however, remain controversial,
      including bracing and knee range of movement. Clinical outcome measures are
      consistently used to judge operative success, but few specialists use defined
      objective measurements such as the IKDC scoring system.

PMID- 11248564
TI  - Correlation between patients' satisfaction and objective measurement of knee
      stability after ACL reconstruction using a patellar tendon autograft.
AB  - We evaluated the relationship between patients' satisfaction and objective
      measurements of knee stability after reconstruction of the ACL using a patellar
      tendon autograft. An examination of 59 patients 2-7 years after surgery was
      carried out. Assessment was made by the Knee and Osteoarthritis Outcome Score for
      patient satisfaction, a modified International Knee Documentation Committee form
      for clinical knee stability and a Telos stress radiography for PA stability. The
      results show that patients' satisfaction was much greater than the objective
      evaluation would suggest. We conclude that documenting mechanical knee stability
      alone is inadequate for follow-up studies and a questionnaire assessing patient
      satisfaction should be added.

PMID- 11248565
TI  - Day surgery anterior cruciate ligament reconstruction: Sheffield experiences.
AB  - A review of the safety, practicality and cost effectiveness of day surgery
      anterior cruciate ligament reconstruction was studied in the British set-up. We
      evaluated 20 patients prospectively who underwent ACL reconstruction as a day
      surgery procedure for pain control, recovery time, post-operative complications
      and cost effectiveness. All patients on a verbal response score (VRS) for pain
      expressed themselves as satisfied or very satisfied. All patients regained a
      range of movement of 0-90 degrees by 1 week and 0-130 degrees by 6 weeks post
      operatively. None of the patients required hospitalisation, only two patients had
      superficial wound infections at the graft-harvesting site. Cost analysis showed
      that day surgery ACL reconstruction was cost effective. The average saving per
      patient was in the range of 20-25% when compared to inpatient ACL reconstruction.

PMID- 11248566
TI  - The effect of flexion angle on the macro and microscopic appearance of the
      rupture surface of the ACL of rabbits.
AB  - This study investigated how knee flexion angle affects the appearance of the
      rupture surface of the anterior cruciate ligament (ACL) using rabbit knees.
      Specimens were failed at flexion angles of 45 degrees and 90 degrees at
      displacement rates of 10 and 500 mm/min. Video recordings and scanning electron
      microscopy (SEM) studied the appearance of the rupture surfaces. At the
      displacement rate of 10 mm/min, the major mode of failure was fibre pullout for
      all flexion angles. At displacement rate of 500 mm/min, which more closely
      approximated loading conditions during trauma, we found that all modes of failure
      were exhibited. At 45 degrees flexion, the majority of specimens tested failed by
      avulsion. The reverse was true for specimens tested at 90 degrees where the
      majority of failures were fibre pullouts. At 45 degrees, there were more pulled
      out fibres on rupture surfaces of specimens tested at 10 mm/min than at 500
      mm/min. At 90 degrees, little difference was seen in the appearance of ruptures
      from both rates. SEM revealed that the waviness of collagen fibres was more
      pronounced at 10 mm/min. Therefore, the appearance of rupture surfaces of ACLs
      are affected by both flexion angle and displacement rate.

PMID- 11248567
TI  - Tibial tunnel enlargement following anterior cruciate reconstruction: does post
      operative immobilisation make a difference?
AB  - The aetiology of tunnel enlargement following anterior cruciate reconstruction is
      still not fully understood. We studied, with particular reference to the tibial
      tunnel appearances, a group of 28 patients 1 year from anterior cruciate
      reconstruction by a four-strand hamstring technique. Fourteen underwent
      accelerated rehabilitation and 14 were immobilised post-operatively for 2 weeks
      following reconstruction. Tunnel enlargement was significantly greater in the
      immobilised group. There was no significant correlation between tunnel
      enlargement and the clinical result at 1-year post-reconstruction.

PMID- 11248568
TI  - Hamstrings vs. patella tendon for anterior cruciate ligament reconstruction: a
      randomised controlled trial.
AB  - A randomised controlled trial was performed to evaluate early outcome for two
      types of anterior cruciate ligament reconstruction. Sixty patients undergoing
      cruciate reconstruction were randomized into two groups. Group PT underwent
      reconstruction using a patella tendon autograft, whereas Group (SG) had a
      semitendinosus/gracilis autograft (SG). IKDC, Lysholm, and Tegner scores, KT1000
      values and muscle strength were recorded pre-operatively, at 6 months and 1 year
      follow up. The functional scores, activity level, muscle strength and anterior
      tibial translation improved in both groups. No significant difference between
      groups was found for any measurement at 6 months and 1 year despite adequate
      study power. The study indicates that the 1 year results for either technique are
      equally favourable.

PMID- 11248569
TI  - Outcome measurement in the ACL deficient knee--what's the score?
AB  - There is increasing pressure within the United Kingdom for transparent assessment
      of the performance of every doctor along with the procedures they perform.
      Unfortunately, the validation of the outcome measures used to assess such
      procedures has been questioned. This has been well illustrated in the anterior
      cruciate ligament (ACL) deficient knee. Over 54 different outcome measures used
      to assess the ACL deficient knee have been identified, few of which were formally
      assessed at their initial publication. For those most frequently used the Lysholm
      (I and II) knee scoring scale and Tegner activity score are the only ones to have
      been adequately validated prior to use. The Cincinnati rating system and
      International Knee Documentation Committee (IKDC) form were not assessed and the
      reliability of both measures has since been questioned. Appropriately tested
      newer measures include the IKDC subjective knee evaluation form, Mohtadi's ACL
      quality of life outcome measure and the Knee injury and osteoarthritis outcome
      score (KOOS). We recommend use of the Lysholm II knee scoring scale and Tegner
      activity score for clinical follow-up of patients and for use as a gold standard
      to which future measures can be compared. These have their deficiencies and will
      ultimately require replacement. In view of the international standing of its
      authors, the IKDC subjective knee evaluation form is likely to be used in
      preference to the KOOS despite its attractions. For long-term clinical trials the
      SF-36 should also be used. Further research is required to produce suitable
      measures for assessing the ACL deficient knee and this work should be
      appropriately funded.

PMID- 11248570
TI  - An audit of tunnel position in anterior cruciate ligament reconstruction.
AB  - We audited 114 primary anterior cruciate ligament (ACL) reconstructions. Notes
      were reviewed and tunnel positions assessed on lateral and AP radiographs. A
      literature review established optimal tunnel position. Sixteen surgeons performed
      57 arthroscopic and 57 open reconstructions, using 24 hamstring and 90 bone
      tendon-bone autografts. Eighty-five sets of radiographs were available for
      review. Sixty-five percent of femoral tunnels and 59% of the tibial tunnels were
      malpositioned in the sagittal plane. Guidelines for best practice are required
      for key procedures in each speciality. Tunnel position in ACL reconstruction can
      be easily measured and should be correct in at least 90% of cases.

PMID- 11248571
TI  - Hamstrings and the anterior cruciate ligament deficient knee.
AB  - This article outlines the background and preliminary results of the work I
      undertook during a year of full time research supported by the BASK Knee Research
      Fellowship. The work was done at the Oxford Orthopaedic Engineering Centre
      (OOEC). The chance to come out of full time clinical work should in my opinion
      always be taken. It allows you time to think in a little more depth about a
      particular area of interest and to work with people in full time research. I
      found that working alongside the Biomechanical Engineers and their PhD students
      was mutually beneficial. They learn more about the background to the clinical
      problems requiring their input, whilst the Orthopaedic trainees undertaking
      projects in the department learnt a more rigorous approach to our methodology.

PMID- 11248572
TI  - BASK Instructional Lecture 1: graft selection in anterior cruciate ligament
      reconstruction.
AB  - It is important to realise that the anterior cruciate ligament (ACL) is a living
      structure which at the present time cannot be truly replaced. It has a purpose
      built, unique anatomical structure with a blood supply and nerve supply including
      proprioception and no substitute currently available can fulfill all of these
      functions.

PMID- 11248573
TI  - BASK Instructional Lecture 2: Long-term effects of anterior cruciate injury.
AB  - The concept than an intact anterior cruciate is needed for normal knee function
      and that its absence is associated with meniscal damage and hyaline cartilage has
      become widely accepted. This evidence for this assumption and the suggested
      effects of surgical reconstruction is presented.

PMID- 11248574
TI  - BASK Instructional Lecture 3: Rehabilitation after ACL reconstruction.

PMID- 11248575
TI  - BASK Instructional Lecture 4: Anterior cruciate ligament graft fixation.
AB  - Anterior cruciate ligament fixation has stimulated an enormous amount of research
      over the last two decades, particularly with the renewed interest of hamstring
      reconstruction. This paper summarises our current knowledge on the variety of
      fixation devices available and points towards possible future advances.

PMID- 11248576
TI  - Pharmacological aspects of targeting cancer gene therapy to endothelial cells.
AB  - Targeting cancer gene therapy to endothelial cells seems to be a rational
      approach, because (a) a clear correlation exists between proliferation of tumor
      vessels and tumor growth and malignancy, (b) differences of cell membrane
      structures between tumor endothelial cells and normal endothelial cells exist
      which could be used for targeting of vectors and (c) tumor endothelial cells are
      accessible to vector vehicles in spite of the peculiarities of the transvascular
      and interstitial blood flow in tumors. Based on the knowledge on the
      pharmacokinetics of macromolecules it can be concluded that vectors targeting
      tumor endothelial cells should own a long blood residence time after
      intravascular application. This precondition seems to be fulfilled best by
      vectors exhibiting a slight anionic charge. A long blood residence time would
      allow the formation of a high amount of complexes between tumor endothelial cells
      and vector particles. Such high amount of complexes should enable a high
      transfection rate of tumor endothelial cells. In view of their pharmacokinetic
      behavior nonviral vectors seem to be more suitable for in vivo targeting tumor
      endothelial cells than viral vectors. Specific binding of nonviral vectors to
      tumor endothelial cells should be enhanced by multifunctional ligands and the
      transduction efficiency should be improved by cationic carriers. Effector genes
      should encode proteins potent enough to induce reactions which eliminate the
      tumor tissue. To be effective to that degree such proteins should induce self
      amplifying antitumor reactions. Examples for proteins which have the potential to
      induce such self-amplifying tumor reactions are proteins endowed with
      antiangiogenic and antiproliferative activity, enzymes which convert prodrugs
      into drugs and possibly also proteins which induce embolization of tumor vessels.
      The pharmacological data for such examples are discussed in detail.

PMID- 11248577
TI  - The role of radionuclides in primary musculoskeletal tumors beyond the 'bone
      scan'.
AB  - Radionuclides represent a means of functional imaging, which is able to reflect
      the metabolic state of tissues. Recently developed radiotracers and older
      radiotracers with newer applications, imaged through single photon emission
      computed tomography (SPECT) and positron emission tomography (PET), can provide
      significant information in the diagnosis, grading, therapy response or recurrence
      of primary musculoskeletal tumors. The unique ability of these radiotracers to
      demonstrate non-invasively the efflux pump rate, which is a common reason of
      therapy failure, as well as the metabolic and proliferative rates of the tumors
      should be a powerful tool in the orthopaedic oncology in the evaluation of
      musculoskeletal tumors.

PMID- 11248578
TI  - Intrathecal chemotherapy.
AB  - An unforeseen consequence of improved disease-free survival in many hematologic
      and solid tumor malignancies has been an increase in the incidence of disease
      recurrence in the leptomeninges. The recognition of the central nervous system
      (CNS) as a unique 'sanctuary' site has resulted in the development of therapeutic
      strategies specifically directed at the leptomeninges. Although therapeutic
      strategies have been successful in the prevention and treatment of CNS leukemia,
      there are still a paucity of therapeutic options for patients with neoplastic
      meningitis due to solid tumors or recurrent CNS leukemia. This article provides
      an overview of the pharmacology and toxicity of intrathecal agents that are
      commonly employed in the treatment and prevention of leptomeningeal disease, and
      describes new agents that are in the early stages of clinical development.

PMID- 11248579
TI  - Taxanes in combined modality therapy for solid tumors.
AB  - The taxanes, paclitaxel and docetaxel, are novel antimitotic agents that are
      under extensive investigation in clinical trials. Both taxanes have demonstrated
      significant activity against many solid tumors as single agents and in
      combination with other chemotherapeutic agents. In addition, taxanes arrest cells
      at the G2/M phase of the cell cycle, which is the most radiosensitive phase.
      These properties are exploited in clinical trials combining this taxane with
      radiation therapy. Most studies included patients with non-small cell lung cancer
      (NSCLC) and cancers of the head and neck and there are a few studies with
      concurrent taxane/RT in esophageal, gastric, pancreatic, brain and breast cancer.
      Information concerning the tolerability and possible utility of docetaxel is also
      becoming available. This manuscript will review some of the more prominent trials
      of the taxanes in combination with radiation therapy for solid tumors.

PMID- 11248580
TI  - Clustering of risk factors for coronary heart disease. the longitudinal
      relationship with lifestyle.
AB  - PURPOSE: The purpose of this study was to investigate whether or not clustering
      of biological coronary heart disease (CHD) risk factors exists and to investigate
      the longitudinal relationship between lifestyle parameters (dietary intake, daily
      physical activity, smoking behaviour, alcohol consumption) and a biological CHD
      risk factor clustering score. This was defined as belonging to one or more gender
      specific 'high risk' quartiles for the following CHD risk factors: ratio between
      total serum cholesterol and high density lipoprotein cholesterol (TC:HDL), mean
      arterial blood pressure (MABP), body fatness [sum of skinfolds (SSF)], and
      cardiopulmonary fitness (VO2-max). METHODS: The data were derived from the
      Amsterdam Growth and Health Study, an observational longitudinal study in which
      six repeated measurements were carried out over a period of 15 years covering
      adolescence and young adulthood. The longitudinal relationships were analysed
      with generalized estimating equations. RESULTS: The results showed significant
      clustering for the TC:HDL ratio, SSF, and VO(2)-max. MABP was not significantly
      associated with the other CHD risk factors. Daily physical activity and alcohol
      consumption (only for males) were both inversely related to the clustering score.
      None of the other lifestyle parameters showed significant relationships with the
      clustering score. CONCLUSIONS: Based on this small longitudinal study, it can be
      stated that during adolescence and young adulthood both daily physical activity
      and alcohol consumption were related to a healthy CHD risk profile.

PMID- 11248581
TI  - Reproducibility of reported farming activities and pesticide use among breast
      cancer cases and controls. A comparison of two modes of data collection.
AB  - PURPOSE: Farming is associated with exposure to many potential hazards including
      pesticides and other agents, but the quality of self-reported data on farm
      exposures has not been well studied. METHODS: The reproducibility of self
      reported farming history was evaluated among women in a population-based, case
      control study of breast cancer in North Carolina. Thirty cases and 31 controls
      were randomly re-interviewed by telephone an average of 13.8 months after the
      initial interview. The initial interview was based on a farm-by-farm
      questionnaire, while the repeat interview was based on a shorter ever/never
      questionnaire. Agreement was estimated using proportions in exact agreement,
      kappa (kappa), and intraclass correlation coefficients (ICC). RESULTS: In
      general, group prevalences and means were higher on re-interview. Kappa estimates
      ranged from 0.15 to 0.84 among cases, and 0.26 to 0.87 among controls, with most
      estimates falling between 0.5 and 0.8. Moderate to almost perfect agreement
      (kappa) was observed for questions on crop work (0.47-0.70), crop type (0.56
      0.82), pesticide application to tobacco (0.77), and farm residence (0.84). ICC
      estimates for continuous variables showed fair to substantial agreement (0.30 to
      0.69 among cases, 0.38 to 0.69 among controls). Older cases, less educated cases,
      cases who lived on more than one farm, and cases with longer time intervals
      between interviews gave lower total agreement than similar groups of controls.
      CONCLUSIONS: Agreement estimates in this study are similar to those for other
      types of exposure information typically collected in epidemiologic studies.
      Nevertheless, a farm-by-farm method of exposure assessment may be preferable to
      an ever/never determination.

PMID- 11248583
TI  - Occupational hierarchy, economic sector, and mortality from cardiovascular
      disease among men and women. Findings from the National Longitudinal Mortality
      Study.
AB  - PURPOSE: Although socioeconomic position has been identified as a determinant of
      cardiovascular disease among employed men and women in the U.S., the role of
      economic sector in shaping this relationship has yet to be examined. We sought to
      estimate the combined effects of economic sector-one of the three major sectors
      of the economy: finance, government and production-and socioeconomic position on
      cardiovascular mortality among employed men and women. METHODS: Approximately
      375,000 men and women 25 years of age or more were identified from selected
      Current Population Surveys between 1979 and 1985. These persons were followed for
      cardiovascular mortality through use of the National Death Index for the years
      1979 through 1989. RESULTS: In men, the lowest cardiovascular mortality was found
      for professionals in the finance sector (76/100,000 person/years). The highest
      cardiovascular mortality was found among male non-professional workers in the
      production sector (192/100,000 person years). A different pattern was observed
      among women. Professional women in the finance sector had the highest rates of
      cardiovascular mortality (133/100,000 person years). For both men and women, the
      professional/non-professional gap in cardiovascular mortality was lower in the
      government sector than in the production and finance sectors. These associations
      were strong even after adjustment for age, race and income. CONCLUSIONS:
      Characteristics of government, finance and production work differentially
      influence the risk of cardiovascular disease mortality. Men, women, professionals
      and non-professionals experience this risk differently.

PMID- 11248582
TI  - Validation of birth certificate data. A study of women in New Jersey's
      HealthStart program.
AB  - PURPOSE: This study assesses the accuracy of 1989-1992 birth certificate data
      from New Jersey for a group of high-risk women. METHODS: Birth records were
      linked to data on women who participated in HealthStart, a program of enriched
      prenatal care for pregnant women on Medicaid. Concordance was assessed for all
      variables common to the two data sets. RESULTS: The birth records had accurate
      reporting of birth-weight, demographic characteristics, and most methods of
      delivery. Prenatal care use was over-reported, and alcohol, tobacco, transfer
      status, medical risk factors, obstetric procedures, as well as complications of
      labor and delivery were underreported. CONCLUSIONS: While many variables are
      reported very accurately on birth certificates, other measures must be used
      cautiously. Analyses using birth certificate data, particularly those focusing on
      high-risk women, need to take the low levels of sensitivity for many risk factors
      into consideration.

PMID- 11248584
TI  - Concordance of stroke symptom onset time. The Second Delay in Accessing Stroke
      Healthcare (DASH II) Study.
AB  - PURPOSE: This study examines the concordance between symptom onset obtained
      during an interview in the emergency department (ED) compared to that recorded in
      the medical record among patients with stroke-like symptoms and characterizes the
      frequency of missing symptom onset information in the medical record. METHODS:
      Interviews with patients presenting with signs and symptoms of acute stroke were
      completed in the ED of seven hospitals to determine symptom onset time. Symptom
      onset recorded in the medical record was abstracted after the patient was
      discharged. RESULTS: Among the patients who presented to the ED with stroke-like
      symptoms, 60.2% overall and 61.9% among stroke patients had a symptom onset date
      and time recorded in the medical record. The Pearson correlation of prehospital
      delay time, comparing symptom onset obtained by interview to that obtained by the
      medical record was 0.80 and among stroke patients was 0.91. Concordance of
      prehospital delay time for stroke within +/- 1 h between the interview and the
      medical record was 60.1%. For stroke patients, concordance was more likely for
      those who had higher functional status prior to the acute episode. CONCLUSIONS:
      Symptom onset time was often missing from the medical record. Standardized and
      systematic recording of delay time in the medical record could increase its
      utility as a clinical measure and as a research tool for acute stroke.

PMID- 11248585
TI  - Postneonatal mortality in Alabama: why no progress in the 90s?
AB  - PURPOSE: To examine the factors associated with postneonatal mortality. METHODS:
      Logistic regression was used to examine the effects of various variables on
      postneonatal mortality in Alabama. RESULTS: The most important predictor of
      postneonatal mortality was birth weight. Social and economic variables were also
      important in explaining postneonatal mortality. CONCLUSIONS: Reductions in
      postneonatal mortality may require closer case management of low birth weight
      neonatal survivors. Survival of these infants creates a cohort at risk of
      postneonatal mortality. Many of these low birth weight infants are born into an
      environment where their mothers' parenting potential is compromised by youth and
      poverty. This may be responsible for the failure to reduce postneonatal mortality
      and explain its increasing proportion of infant deaths; deaths may be being
      postponed from the neonatal to the postneonatal period.

PMID- 11248586
TI  - Food composition and empirical weight methods in predicting nutrient intakes from
      food frequency questionnaire.
AB  - PURPOSE: Although the empirical weight (regression-based) method has theoretical
      advantages over the traditional food composition method in predicting nutrient
      levels from food frequency questionnaires (FFQs), the empirical assessments have
      been limited. METHODS: We compared the validity of the two approaches for a 44
      item questionnaire used in a population-based prospective study in Japan. Based
      on four 7-day diet records and questionnaire responses collected from a subsample
      of the prospective study (94 men and 107 women), we developed a food composition
      table and stepwise regression models to predict intakes of energy and 14
      nutrients from the questionnaire. RESULTS: When we applied the two methods to an
      independent population (207 men and 166 women) providing a 3-day diet record and
      responding to a 36-item dietary questionnaire, energy-adjusted and deattenuated
      correlation coefficients between the questionnaire and the diet records were not
      higher for the empirical weight method than for the food composition method; the
      median (range) was 0.22 (0.07-0.57) for men and 0.23 (-0.09-0.62) for women in
      the former method, and 0.26 (-0.04-0.58) for men and 0.38 (0.18-0.67) for women
      in the latter method. CONCLUSIONS: We did not find the improved validity of FFQ
      by empirical weight method in predicting nutrient intakes.

PMID- 11248588
TI  - The parkin gene S/N167 polymorphism in Australian Parkinson's disease patients
      and controls.
AB  - This study determined the frequencies of a G-to-A transition (S/N167)
      polymorphism in exon 4 of the parkin gene in Australian Parkinson's disease
      patients and control subjects. The genotype of each subject was determined using
      the polymerase chain reaction and restriction-fragment-length-polymorphism
      analysis. Overall, the A allele was significantly less common in the Parkinson's
      disease group (1.7%) compared with the control group (3.8%, OR=0.43, 95% CI=0.19
      1.00, P<0.05), although the frequency in the young onset Parkinson's disease
      group (6.6%) was not significantly different to controls. The A allele is less
      common in Australian Caucasian subjects compared to Japanese Parkinson's disease
      patients and appears to be under-represented in older-onset Parkinson's disease.

PMID- 11248587
TI  - Positron emission tomography in pallido-ponto-nigral degeneration (PPND) family
      (frontotemporal dementia with parkinsonism linked to chromosome 17 and point
      mutation in tau gene).
AB  - Pallido-ponto-nigral degeneration (PPND) is a rapidly progressive disorder
      characterized by frontotemporal dementia with parkinsonism unresponsive to
      levodopa therapy. In this study, we have further characterized the regional
      abnormalities of cerebral function using PET with 6-[18F]fluoro-L-dopa (FD),
      [11C] raclopride (RAC), and 2-deoxy-2-fluoro-[18F]-D-glucose (FDG). FD and RAC
      scans were performed in 3 patients-2 new patients and a previously reported
      asymptomatic at-risk individual who became symptomatic 2years after the first FD
      scan. Cerebral glucose metabolism was studied by FDG in 2 other patients. In
      keeping with previous reports, there was a severe reduction of FD uptake, which
      affected both caudate and putamen to a similar degree in all 3 patients. RAC
      scans showed normal to elevated striatal D2-receptor binding in all patients.
      Cerebral glucose metabolism was globally reduced (>2 SD below control mean) in
      one patient, with maximal involvement of frontal regions, and to a lesser degree
      in the other patient. Our study showed severe presynaptic dopaminergic
      dysfunction with intact striatal D2 receptors in PPND patients, implying that the
      dopa unresponsiveness is probably a result of pathology downstream to the
      striatum. The pattern of presynaptic dysfunction contrasts with that seen in
      idiopathic parkinsonism, where the putamen is affected more than the caudate
      nucleus. The pattern of glucose hypometabolism correlates well with the presence
      of frontotemporal dementia.

PMID- 11248589
TI  - Tolcapone increases plasma catecholamine levels in patients with Parkinson's
      disease.
AB  - Tolcapone is a catechol-ortho-methyl-tranferase (COMT) inhibitor that increases
      the L-DOPA half-life and the duration of effect in Parkinson's disease. We
      investigated the effect of tolcapone on the plasma catecholamine levels. We
      measured plasma catecholamines 2h after the first daily dose of L-DOPA or L
      DOPA+tolcapone while resting and 2 and 10min after standing. We also measured the
      pharmacokinetics of L-DOPA and 3-OM-DOPA and the clinical response to the
      medication for 6h after the early morning dose. The levels of dopamine,
      norepinephrine, adrenaline and total catecholamines significantly increased and 3
      OM-DOPA decreased with tolcapone. We did not observe significant changes in the
      plasma L-DOPA levels at the doses of tolcapone used in this study. Tolcapone side
      effects included worsening of dyskinesia and psychosis, diarrhea and elevation of
      liver enzymes. Twenty-four-hour ambulatory recording of arterial blood pressure
      and heart rate did not reveal cardiovascular side effects in patients treated
      with tolcapone for less than 1year. Since adrenergic stimulation may increase the
      hepatotoxic potential of commonly used drugs, usually thought of as safe for the
      liver, we postulate that some of the already reported life threatening
      complications of tolcapone could be related to excessive adrenergic stimulation
      by high catecholamine levels caused by inhibition of COMT activity.

PMID- 11248590
TI  - Neonatal iron potentiates adult MPTP-induced neurodegenerative and functional
      deficits.
AB  - The interactive effects of neonatal iron and adult MPTP treatment groups of C57
      Bl/6 mice were studied through adminustration of iron (Fe(2+)) 7.5mg/kg b.w.,
      p.o. or vehicle (saline) on days 10-12 post partum, followed at 3months of age by
      administration of either MPTP (2x20 or 2x40mg/kg, s.c.) or saline. Neonatal iron
      administration to mice-induced hypoactivity during the first 20-min period of
      testing and hyperactivity during the 3rd and final 20-min period for all three
      parameters of motor activity tested at 4months of age. MPTP treatment caused a
      dose-related hypokinesia throughout the 3x20-min test periods; in the mice that
      received both neonatal iron and MPTP severe deficits of motor activity (akinesia)
      were obtained. Iron treatment impaired the ability of mice to habituate to the
      novel testing environment and later administration of MPTP potentiated the
      impairment markedly. Neurochemical analyses of striatal and frontal cortical
      dopamine (DA) and DA metabolites demonstrated that the depletions were
      potentiated under conditions of combined neonatal iron and adult MPTP. The
      analysis of total iron content (ug/g) in brain regions indicated notably elevated
      levels in the basal ganglia, but not in the frontal cortex, of mice administered
      Fe(2+). Iron-overload combined with MPTP treatment induced functional and
      neurochemical deficits with interactive consequences beyond a mere additive
      effect that may have implications for the neurodegenerative process in
      parkinsonism.

PMID- 11248591
TI  - Levodopa or dopamine agonists, or deprenyl as initial treatment for Parkinson's
      disease. A randomized multicenter study.
AB  - Objectives: levodopa improves the quality of life in parkinsonian patients,
      however long term response is compromised by the emergence of motor fluctuations
      and dyskinesias. The aim of this study was to compare the occurrence of motor
      fluctuations and dyskinesias in previously untreated patients assigned to receive
      levodopa, a dopamine agonist or deprenyl.Thirty-five neurological departments in
      Italian hospitals participated in this randomized open trial. Patients with
      Parkinson's disease, who required the initiation of an effective antiparkinsonian
      treatment, were randomly assigned to receive levodopa, dopamine agonists or
      deprenyl. The end-points were motor dyskinesias and motor fluctuations occurring
      in a median follow-up period of about 3years.After a median follow-up of
      34months, motor fluctuations and dyskinesias were less frequent in patients
      assigned to a dopamine agonist or deprenyl than in patients assigned to levodopa
      (relative risk [RR] 0.5, 95% confidence interval [95% CI] 0.3-0.8, and RR=0.6,
      95% CI 0.3-0.9, respectively), but dopamine agonists were less effective and less
      well tolerated than levodopa. The lower frequency of motor fluctuations in
      patients assigned to deprenyl was no longer statistically significant when
      prognostic predictors were considered in a multivariable analysis. Long-term
      mortality did not differ in the three arms of the study. Dopamine agonists and
      deprenyl can be considered as an alternative to levodopa for starting treatment
      in Parkinson's disease patients. However, on clinical grounds, only small
      advantages are expected over the traditional therapy initiation with levodopa.

PMID- 11248592
TI  - The long-term safety and efficacy of pramipexole in advanced Parkinson's disease.
AB  - Objective: To assess the long-term safety and efficacy of pramipexole in advanced
      Parkinson's disease over a four year time period.Methods: This study is an open
      label extension trial of pramipexole for Parkinson's disease open to patients
      completing a double-blind placebo controlled safety and efficacy trial of this
      drug. Three hundred and six patients entered the trial. These patients had
      moderate to severe PD (stage II-IV Hoehn and Yahr during off time) and were
      experiencing motor fluctuations. Patients were titrated over a six week period
      and then entered a maintenance phase which lasted up to 50 months. Patients were
      evaluated every 3 months using the Unified Parkinson's Disease Rating Scale
      (UPDRS II, III and IV) and modified Schwab and England scale (S/E).Results: Sixty
      four percent (197) of the 306 patients who entered this study completed it.
      Patients showed steady improvement over the 6 week ascending dose interval when
      pramipexole was reintroduced into the trial as the open-label study medication.
      Over the duration of the trial patients slowly returned to their baseline levels.
      This was true for all measures evaluated except for the UPDRS part IV. On UPDRS
      part IV patients remained below their baseline score which indicated an
      improvement for the duration of the study. Patterns similar to the overall scores
      were seen when the individual components of the UPDRS scale part II for "on" and
      "off" periods and part III were evaluated. However tremor during "on" periods
      showed improvement over baseline for the duration of the trial. The most common
      adverse events secondary to pramipexole occurring in greater than 10% of patients
      included dyskinesias, asymptomatic orthostatic hypotension, dizziness, insomnia,
      and hallucinations.Conclusion: Pramipexole was well tolerated for up to 4 years.
      Pramipexole treatment appeared to show continued efficacy in the treatment of
      Parkinson's disease for 3 years in this open-label descriptive study. After 3
      years there was a gradual return to baseline motor states perhaps suggesting
      progression of Parkinson's disease.

PMID- 11248593
TI  - Efficacy and safety of clozapine and olanzapine: an open-label study comparing
      two groups of Parkinson's disease patients with dopaminergic-induced psychosis.
AB  - Clozapine, an atypical neuroleptic agent, improves dopaminergic-induced psychosis
      in parkinsonian patients without increasing motor disability. However, because of
      the risk of agranulocytosis periodic hematological controls are mandatory.
      Olanzapine, another atypical neuroleptic, does not require such monitoring, which
      may represent a practical advantage. Therefore, for 12weeks we compared the
      tolerability and efficacy of clozapine and olanzapine in two groups of nine
      consecutive parkinsonian psychotic patients treated with these compounds. All the
      patients on clozapine (mean starting dose: 13.1+/-7.9mg/d) completed the study
      despite reporting a number of adverse events, including somnolence, falls,
      orthostatic hypotension, and syncope. In contrast, early withdrawal occurred in
      three of the nine patients receiving olanzapine, due to severe gait deterioration
      and drowsiness (mean starting dose: 3.9+/-1.3mg/d). Psychotic symptoms improved
      in both groups, as reflected by a reduction of 71.7% in clozapine and a 61.7%
      reduction in olanzapine, in five selected items from the Neuropsychiatric
      Inventory. On conclusion of the study, parkinsonism had improved in the clozapine
      group with a 19.7% decrease in the raw scores and a 7.9% decrease in the weighted
      scores according to the Cornell University Rating Scale for parkinsonism (mean
      dose: 16.9+/- 10.3mg/d). Conversely, the six patients receiving olanzapine who
      finished the study experienced aggravated parkinsonian symptoms, with a 25.5%
      worsening in the raw scores and a 24.6% worsening in the weighted scores (mean
      dose: 4.7+/-2.3mg/d). We postulate that the early drop-outs in the olanzapine
      treated parkinsonian group may be attributable to a non-specific effect of the
      drug as a result of starting at too high a dose, and that the worsening of
      parkinsonism following prolonged treatment may have been caused by the drug's
      blocking effect on striatal D2 receptors.

PMID- 11248594
TI  - Gender ratio differences between Parkinson's disease patients and their affected
      relatives.
AB  - Mitochondrial dysfunction in Parkinson's disease (PD) is suspected to arise from
      either acquired or inherited mutation of mitochondrial DNA (mtDNA). If inherited,
      epidemiologic analysis may reveal maternal transmission. We looked for maternal
      inheritance bias in our PD clinical database. About 13% of 600 PD probands
      reported an affected parent. Although 60% of the PD probands were male, only 42%
      of the affected parents were. The gender ratios for the proband and affected
      parent generations were dissimilar (p<0.005), indicating an underrepresentation
      of affected fathers or an overrepresentation of affected mothers. To address
      these possibilities we analyzed a non-PD control cohort. Four percent of the
      controls had a PD affected parent, and 75% of these affected parents were male.
      Apparent maternal inheritance bias in our PD cohort is therefore more likely due
      to overrepresentation of affected mothers, and is consistent with mitochondrial
      inheritance in some of our ascertained cases.

PMID- 11248595
TI  - Gait festination in Parkinson's disease.
AB  - Background: Festinating gait (FSG) was first associated with parkinsonism by Sir
      James Parkinson, in his original essay on "The Shaking Palsy". Its frequency and
      relation to other parkinsonian features have never been assessed.Objective: To
      study the relationships between gait festination and other parkinsonian clinical
      features among patients with Parkinson's disease (PD).Method: During an open
      lecture to patients with PD who are followed at the Movement Disorders Unit (MDU)
      of Tel-Aviv Sourasky Medical Center one of us explained verbally and imitated
      festinating gait on stage. All attending patients with the help of their care
      givers or family members, were asked to answer two written questions regarding
      their own experience with FSG as well as the degree of disability it causes.
      Clinical information about each patient was taken from his/her chart at the MDU
      and missing data was completed during the next office visit or from the family
      physician. Statistical analysis was performed using t-tests for comparison
      between groups, Chochran-Armitage test for trends and logistic regression to
      assess the contribution of age of onset, disease duration and disease severity to
      the development of FSG.Results: Eighty-one PD patients (58 males, mean age 67.5+/
      10.7years) answered the FSG questionnaire. Our study population's mean disease
      duration was 8.5+/-6.4years, mean Hoehn and Yahr (H&Y) clinical stage of 2.6+/
      0.8 and mean levodopa dose of 608+/-375mg/day (15 patients were not on levodopa).
      Twenty-six patients (32.1%) experienced FSG during the previous month and 56% of
      them reported that FSG was a significant and disabling symptom. FSG was strongly
      associated with higher stage of H&Y (p<0.001) with a significant trend as the
      disease progresses (p=0.001) but not with total score in the motor part of the
      Unified Parkinson's Disease Rating Scale (UPDRS). Longer disease duration was the
      only clinical factor, which was found to be associated with FSG in the
      multivariate model. Thirty seven percent (37%) of the patients with FSG reported
      frequent falls with association between occasional or frequent falls, as reported
      on the activity of daily living (ADL) part of the UPDRS, and the presence of FSG
      (p<0.08). There was no association between significant postural reflex
      abnormalities as rated on the objective part of the UPDRS and the presence of
      FSG. There was a significant association between the presence of freezing of gait
      (FOG) as reported in the ADL part of the UPDRS and the presence of FSG (p<0.001)
      as well as a significant trend towards more frequent FSG in patients with more
      severe FOG (p<0.001).Conclusion: FSG was clearly associated with longer duration
      of PD symptoms but not with disease severity as reflected in the motor part of
      the UPDRS. The relationships between FSG and postural reflexes abnormalities is
      unclear but it is frequently associated with falls and freezing of gait.

PMID- 11248596
TI  - Antiphospholipid syndrome and dystonia-parkinsonism. A case report.
AB  - Background: Although clinically evident and MRI confirmed, basal ganglia
      involvement, is usual in primary antiphospholipid syndrome, extrapyramidal
      disorders such as parkinsonism and dystonia are very rare. We were unable to find
      any report in the literature on dystonia-parkinsonism in patients with primary
      antiphospholipid syndrome. Here we report an adult patient with dystonia
      parkinsonism and primary antiphospholipid syndrome.Case report: A 60 year old,
      right-handed man came to our attention due to writer's cramp, bradykinesia and
      stiffness of his right hand. Neurological examination revealed constant, marked
      dystonic posturing, rigidity and bradykinesia of the right hand. Hyper
      gammaglobulinemia was demonstrated on electrophoresis-serum IgG was increased.
      Anticardiolipin antibodies were examined by counterimmunoelectrophoresis (ELISA):
      IgG was negative, while IgM was positive. There was also slight thrombocytopenia.
      Magnetic resonance imaging brain scan axial T2W/UTSE revealed several
      hyperintense lesions in the basal ganglia and in the periventricular white matter
      and diffuse hyperintensity of the subcortical white matter bilaterally in the
      parietal regions. There was asymmetric parenchimal atrophy, more prominent in the
      left hemisphere. No clinical improvement was achieved by levodopa, dopamine
      agonists or anticholinergics. According to the criteria for primary
      antiphospholipid syndrome our patient had thrombocytopenia and high levels of IgG
      and IgM anticardiolipin antibodies so he was presumed to have a primary
      antiphospholipid syndrome.Conclusion: Various movement disorders may appear
      secondary to stroke, antiphospholipid syndrome, Behcet's disease or brain tumor.
      These cases may help in the understanding of pathophysiology of movement
      disorders. Dystonia and parkinsonism as well as other movement disorders may be
      associated with primary antiphospholipid syndrome.

PMID- 11248597
TI  - Prehension patterns in restless legs syndrome patients.
AB  - The pathogenesis of restless legs syndrome (RLS) is poorly understood. Previously
      we have shown that a reach-to-grasp task can be used to differentiate Parkinson's
      disease (PD) patients from healthy age-matched control subjects. The aim of this
      study was to determine if performance on this task could be used to differentiate
      between patients with RLS, PD patients, and healthy control subjects. Results
      indicated that RLS and control participants produced movement patterns that were
      nearly identical to one another, while movement patterns produced by the PD
      patients were significantly different from the other two groups. These results
      suggest RLS patients do not show any abnormalities in the performance of upper
      extremity prehension movements. Thus, these movements can be used to effectively
      differentiate between patients with Parkinson's Disease and Restless Legs
      Syndrome. While RLS patients respond favorably to dopaminergic therapies, this
      study suggests that PD and RLS may not share the same basal ganglia
      pathophysiology.

PMID- 11248598
TI  - "Management of behavioral and psychiatric problems in Parkinson's disease" by A.
      A. Rabinstein, L. M. Shulman. Parkinsonism & Related Disorders 7(1) pp. 41-50.

PMID- 11248599
TI  - E-health: transforming the physician/patient relationship.
AB  - Healthcare delivery is being transformed by advances in e-health and by the
      empowered, computer-literate public. Ready to become partners in their own health
      and to take advantage of online processes, health portals, and physician web
      pages and e-mail, this new breed of consumer is slowly redefining the
      physician/patient relationship. Such changes can effect positive results like
      improved clinical decision-making, increased efficiency, and strengthened
      communication between physicians and patients. First, however, physicians and the
      organizations that support them must fully understand their role in the e-health
      revolution. Both must advance their awareness of the new consumers and their
      needs and define specific action items that will help them realize the benefits
      of e-health. Through a combination of timely research and advice, this article
      will aid them in fulfilling both tasks.

PMID- 11248600
TI  - A computerised information system for the analysis of hospital admission flow and
      characteristics.
AB  - This paper presents a computerised information system for the characterisation
      and analysis of the hospital admission flow of patients. Based on administrative
      data made available by the Ministry of Health of Brazil (DATASUS-MS), the system
      allows the representation of patients' flow from residence to hospital, as well
      as information on performed medical procedures, diagnoses and other patient and
      hospital characteristics. Residences are represented in terms of their postal
      codes and admission diagnosis according to the ICD-10 classification. The system
      has a flexible and simple geographic coordinates input module, and can be used
      even when no standard coordinates system (e.g., Mercator) are available. It
      provides two types of graphical representation: 'static' (concerning
      characteristics of a hospital or geographical area) and 'dynamic' (residence to
      hospital flow). Its use is exemplified with a geographical representation of
      access to ultra-sound exams in selected hospitals in the city of Rio de Janeiro,
      Brazil, July 1998. In conclusion, the system seems a powerful instrument for
      health needs identification and planning, as well as for quality assessment and
      for the generation of information useful for epidemiological research.

PMID- 11248601
TI  - A computerized method for identifying incidents associated with adverse drug
      events in outpatients.
AB  - INTRODUCTION: In inpatients, computer monitors have been used to improve the
      detection of adverse drug events (ADEs). However, similar programs have not been
      available in outpatients. OBJECTIVE: To describe an approach for detecting
      incidents suggesting that an ADE may have occurred in outpatients by adapting
      methods from inpatient computer monitoring and developing terminology searches of
      electronic medical records. METHODS: One year of information from the outpatient
      electronic medical record (EMR) at one hospital and its clinics was reviewed.
      Altogether, 23064 patients and 88514 visits were identified. Patient
      demographics, medical problem lists, ICD-9 claims, patient allergies, medication
      history and all clinic visit notes were extracted and merged. We then searched
      for incidents suggesting that an ADE might be present using four methods: ICD-9
      claims, new allergies, computer rules linking laboratory data to known medication
      exposures, and a medical terminology lexicon (M2D2). In this report, we describe
      how these search methods were developed to allow for ADE identification.
      CONCLUSION: The ability to carry out such quality-related work is an example of
      the benefits of the outpatient EMR that may not be apparent to those institutions
      considering adopting it.

PMID- 11248602
TI  - Slovene smart card and IP based health-care information system infrastructure.
AB  - Slovenia initiated a nation-wide project to introduce smart cards in the health
      sector in 1995 and its full-scale deployment started in September 2000. Although
      the basic aim of the project was to support insurance related procedures, the
      system was designed in a flexible and open manner to present an infrastructure
      for the whole health sector. The functionality of the current system is described
      in this paper along with lessons learned so far. The upgrade of the system is
      outlined, with emphasis on technical details, the objective being to provide a
      real-time EDI based environment for a general set of applications in the medical
      sector, supported by the flexibility and security of modern smart card
      technologies. Integration with similar systems in other EU countries is
      discussed.

PMID- 11248603
TI  - 'Televaluation' of clinical information systems: an integrative approach to
      assessing Web-based systems.
AB  - The World Wide Web provides an unprecedented opportunity for widespread access to
      health-care applications by both patients and providers. The development of new
      methods for assessing the effectiveness and usability of these systems is
      becoming a critical issue. This paper describes the distance evaluation (i.e.
      'televaluation') of emerging Web-based information technologies. In health
      informatics evaluation, there is a need for application of new ideas and methods
      from the fields of cognitive science and usability engineering. A framework is
      presented for conducting evaluations of health-care information technologies that
      integrates a number of methods, ranging from deployment of on-line questionnaires
      (and Web-based forms) to remote video-based usability testing of user
      interactions with clinical information systems. Examples illustrating application
      of these techniques are presented for the assessment of a patient clinical
      information system (PatCIS), as well as an evaluation of use of Web-based
      clinical guidelines. Issues in designing, prototyping and iteratively refining
      evaluation components are discussed, along with description of a 'virtual'
      usability laboratory.

PMID- 11248604
TI  - A survey of patient-provider e-mail communication: what do patients think?
AB  - Communication between patients and providers forms the backbone of the patient
      provider relationship. Often such communication is strained due to time and space
      limitations on the part of both patients and providers. Many healthcare
      organizations are developing secure e-mail communication facilities to allow
      patients to exchange e-mail messages with their providers. Providers are worried
      that opening such lines of communication will inundate them with vast quantities
      of e-mail from their patients. Patients are worried that their messages will be
      intercepted and read by unauthorized people. In an attempt to determine how a
      group of internet-active, e-mail-ready patients currently use, or potentially
      view, the ability to exchange e-mail messages with their health care providers,
      we distributed a survey via e-mail to over 9500 patients. After determining each
      patient's e-mail activity level (based on the number of messages sent each day),
      we asked questions such as: "Have you ever sent e-mail to your provider?" "What
      issues or concerns have prevented you from sending e-mail messages to your
      provider?" "If your provider were to tell you that someone in his/her office may
      screen, read or perhaps reply to your message before he/she sees it, to what
      extent would you be concerned about this?" and "How would you rate your overall
      satisfaction with the use of e-mail to communicate with your provider?" Results
      from the survey indicate that nearly 85% of the patients surveyed send at least
      one e-mail message per day, but that very few (i.e. 6%) of the patients have
      actually sent an e-mail message to their provider. Interestingly, over half of
      the patients indicated that they would like to send their providers e-mail, but
      that they do not know their provider's e-mail address.

PMID- 11248605
TI  - Indium-111-capromab pendetide scans: an important test relevant to clinical
      decision making.

PMID- 11248606
TI  - PROSTASCINT scan for staging prostate cancer.

PMID- 11248607
TI  - Cranberry juice and urinary tract infections: what is the evidence?

PMID- 11248608
TI  - Tolterodine once-daily: superior efficacy and tolerability in the treatment of
      the overactive bladder.
AB  - OBJECTIVES: To evaluate the efficacy and tolerability of a new extended-release
      (ER), once-daily, capsule formulation of tolterodine, relative to placebo and the
      existing immediate-release (IR), twice-daily, tablet formulation, for treatment
      of the overactive bladder. METHODS: This was a double-blind, multicenter,
      randomized, placebo-controlled trial. One thousand five hundred twenty-nine
      patients (81% women) with urinary frequency (eight or more micturitions every 24
      hours) and urge incontinence (five or more episodes per week) were randomized to
      oral therapy with tolterodine ER 4 mg once daily (n = 507), tolterodine IR 2 mg
      twice daily (n = 514), or placebo (n = 508) for 12 weeks. Efficacy was assessed
      at the end of the treatment period on the basis of the micturition diary
      variables. Tolerability and safety were assessed by evaluating the adverse
      events, electrocardiogram parameters, laboratory values, and treatment
      withdrawals. RESULTS: Tolterodine ER 4 mg once daily (P = 0.0001) and tolterodine
      IR 2 mg twice daily (P = 0.0005) both significantly reduced the mean number of
      urge incontinence episodes per week compared with placebo. The median reduction
      in these episodes as a percentage of the baseline values was 71% for tolterodine
      ER, 60% for tolterodine IR, and 33% for placebo. The ER formulation was 18% more
      effective than the IR formulation (P <0.05). Treatment with both formulations of
      tolterodine was also associated with statistically significant improvements in
      all other micturition diary variables compared with placebo. For both
      formulations, the mean decreases in micturition frequency (P <0.0079) and pad
      usage (P <0.0145) were significant, and the mean volume voided per micturition
      increased (P = 0.0001). The rate of dry mouth (of any severity) was 23% for
      tolterodine ER, 30% for tolterodine IR, and 8% for placebo. The overall dry mouth
      rate for patients taking tolterodine ER was 23% lower than for tolterodine IR (P
      <0.02), and the rate of severe dry mouth in the ER group was only 1.8%. The rates
      of withdrawal were comparable for the two active groups and the placebo group. No
      safety concerns were noted. CONCLUSIONS: Tolterodine ER 4 mg once daily is
      effective and well tolerated in the treatment of overactive bladder with no
      safety concerns. Tolterodine ER demonstrated an improved efficacy for reducing
      urge incontinence episodes and a lower frequency of dry mouth compared with the
      existing IR twice-daily formulation.

PMID- 11248609
TI  - Stress and symptoms in patients with interstitial cystitis: a life stress model.
AB  - Objectives. Stress-related exacerbation of interstitial cystitis (IC) symptoms
      has frequently been reported. Previous research has found stress-related IC
      symptom exacerbation in an experimental model. However, this relationship has not
      been objectively examined with daily life stressors. We used a prospective daily
      symptom diary method to investigate the relationships among stress and bladder
      symptoms in patients with IC and age-matched healthy controls.Methods. Forty-five
      previously diagnosed female patients with IC completed a bladder symptom and
      stress diary nightly for 1 month; 31 female age-matched healthy controls
      completed a similar diary for 7 days. The symptom questions were modified from
      the Interstitial Cystitis Data Base study.Results. Patients reported greater mean
      daily stress, bladder pain, urgency, and daytime and nocturnal frequency than
      controls (all P values less than 0.001). Among all patients, a significant
      relationship between stress and urgency was observed. In addition, a significant
      relationship between stress and pain was observed among patients with moderate
      and severe disease. As the disease severity increased, more pronounced
      relationships between stress and the symptoms of urgency and pain were evidenced.
      Greater stress was associated with greater nocturnal frequency among patients
      with more severe disease. These stress-symptom relationships were not observed
      among the controls.Conclusions. Higher levels of stress were related to greater
      pain and urgency in patients with IC but not in the controls. In addition, the
      relationship of stress and these IC symptoms was stronger among patients with
      more severe disease. The results indicate that life stress is associated with
      greater IC symptoms, particularly among patients whose disease is not well
      controlled.

PMID- 11248610
TI  - Intravesical potassium sensitivity in patients with interstitial cystitis and
      urethral syndrome.
AB  - OBJECTIVES: To examine populations with diagnosed clinical interstitial cystitis
      (IC) and urethral syndrome and normal controls using the potassium sensitivity
      test (PST), to determine the incidence of PST-provoked pain and/or urgency, and
      to document the type and location of IC and urethral syndrome pain, association
      of pain with sexual intercourse, and family history of female urgency/frequency
      problems. METHODS: The PST and a questionnaire were administered to 466 patients
      with clinical IC, 116 patients with urethral syndrome, and 42 controls. RESULTS:
      The PST was positive in 78% of patients with clinical IC, in 55% of patients with
      urethral syndrome, and in 0% of the controls. Of the patients with clinical IC,
      9% responded to the PST with pain only and 8% with urgency only. Patients with
      clinical IC reported the pain as dysuria (58%), urethral/vaginal (76%), above the
      pubic bone (53%), lower abdomen (47%), lower back (35%), vaginal (51%), and
      inguinal (28%). The results were similar for patients with urethral syndrome. Of
      the sexually active men and women, 71% with clinical IC and 59% with urethral
      syndrome reported pain associated with intercourse. Urgency/frequency problems in
      female relatives were reported by 35% of patients with IC and 33% of those with
      urethral syndrome. CONCLUSIONS: The significant potassium sensitivity in both
      patients with clinical IC and those with urethral syndrome and the absence of
      potassium sensitivity in normal controls indicates that a positive PST suggests
      the presence of an abnormal bladder epithelium. The lower rate of positive PSTs
      in patients with urethral syndrome reflects the less severe, more intermittent,
      nature of the symptoms in urethral syndrome (early IC). Pelvic pain of bladder
      origin may occur anywhere in the pelvis. Finally, IC appears to have a genetic
      component.

PMID- 11248613
TI  - Preliminary evaluation of calcium hydroxylapatite as a transurethral bulking
      agent for stress urinary incontinence.
AB  - OBJECTIVES: To evaluate the potential of calcium hydroxylapatite particles as a
      bulking material for the treatment of stress incontinence. METHODS: Ten women
      (mean age 68 years, range 60 to 82) with stress incontinence associated with
      intrinsic sphincter deficiency and limited hypermobility were treated with one (3
      patients) or two (7 patients) injections of calcium hydroxylapatite particles and
      were followed up for 1 year subsequent to the last injection. RESULTS: The mean
      total volume injected was 3.9 mL. No significant safety issues were identified
      with regard to local pain, infection, induration, or obstruction. Seven women
      reported substantial improvement using many fewer pads or none at all (3
      patients) at 1 year, 2 women reported fewer pads, and 1 patient reported no
      change. The daily mean pad use declined from 2.59 to 1.64 and the mean 24-hour
      pad weight declined by more than 90% (104.9 versus 1.5 g). The mean Valsalva leak
      point pressure (VLPP) increased from 39 to 46 cm H(2)O at 12 months, with 2
      patients dry on testing. CONCLUSIONS: The results of this small initial study
      suggest that calcium hydroxylapatite particles have potential as a bulking agent
      for the treatment of stress incontinence.

PMID- 11248615
TI  - Impact of urethral injury management on the treatment and outcome of concurrent
      pelvic fractures.
AB  - OBJECTIVES: Multiple treatment options exist for concurrent posterior urethral
      trauma and pelvic fractures. Because of the increased risk of contamination, the
      surgical repair of fractures may be prohibited by suprapubic urologic catheters.
      To characterize the incidence and long-term outcomes of these management
      conflicts, we reviewed our experience with concomitant pelvic fractures and
      posterior urethral injuries. METHODS: For a 42-month period, 61 patients with
      concurrent lower urinary tract and pelvic trauma, including 23 with posterior
      urethral injuries, were retrospectively reviewed for conflicts between urologic
      management and optimal treatment of the associated orthopedic injuries. RESULTS:
      Of the 23 posterior urethral injuries identified, the management of 8 (35%) was
      noted to impact the decision regarding the management and outcome of the
      concurrent pelvic fractures. Although the overall difference in the length of
      hospitalization and period of immobilization was not statistically significant,
      of the 4 patients whose suprapubic catheter precluded surgical orthopedic
      fracture repair, 3 patients (75%) remain disabled because of chronic pelvic pain,
      and none of those who underwent early endoscopic realignment remain disabled
      because of their pelvic fracture. CONCLUSIONS: Endoscopic realignment for
      traumatic posterior urethral injuries associated with pelvic fractures,
      particularly acetabular fractures, should be attempted to avoid the increased
      morbidity associated with conservative management of the concurrent orthopedic
      injuries.

PMID- 11248616
TI  - Retroperitoneal laparoscopic versus open pyeloplasty with a minimal incision:
      comparison of two surgical approaches.
AB  - OBJECTIVES: To compare the complications, hospital stay, and functional results
      of retroperitoneal laparoscopic (RL) pyeloplasty versus open pyeloplasty (OP)
      with a minimal subcostal incision. METHODS: From October 1997 to January 2000, 53
      consecutive nonrandomized patients underwent 26 RL pyeloplasties, of which 1 was
      bilateral (group 1), and 28 OP (group 2). The decision between the two techniques
      depended on the patient's anesthetic ability to tolerate RL, previous
      ureteropelvic junction surgery, associated renal pathologic findings, and the
      surgeon's laparoscopic experience. Subjective outcomes as to postoperative pain
      and convalescence and objective findings on intravenous urography were assessed
      at 3 months postoperatively in both groups. RESULTS: The mean operating time (165
      versus 145 minutes) and mean blood loss (92 versus 84 mL) were similar in both
      groups. No intraoperative complications occurred in either group; in group 1, 1
      patient required open conversion. Postoperative complications occurred in 11.5%
      of group 1 and 14.3% of group 2. The mean hospital stay was 4.5 days for group 1
      and 5.5 days for group 2. At 3 months, 23 patients (92%) in group 1 and 25
      (89.2%) in group 2 were pain-free or improved. Intravenous urography showed a
      patent ureteropelvic junction in all cases and improvement of hydronephrosis in
      88.5% of group 1 and 89.3% of group 2. CONCLUSIONS: The incidence of
      complications, hospital stay, and functional results were equivalent for RL
      pyeloplasty and OP with a minimal incision, but the return to painless activity
      was more rapid with laparoscopy in younger patients.

PMID- 11248618
TI  - Laparoscopic nephroureterectomy for the treatment of transitional cell carcinoma
      of the upper urinary tract.
AB  - OBJECTIVES: To establish the safety and efficacy of laparoscopic and laparoscopic
      assisted nephroureterectomy. METHODS: Since 1993, 25 patients with a minimum of
      12 months of follow-up underwent nephroureterectomy using a total laparoscopic or
      laparoscopic-assisted technique. Four patients had specimen morcellation for
      tissue removal. All patients had regular follow-up with physical examinations,
      interval cystoscopy, and radiographs, depending on the metastatic potential of
      the tumor. Retrospective chart review was performed and assessed for operative
      time, blood loss, tumor pathologic stage, complications, and outcome. One patient
      was excluded because of an open conversion due to multiple previous abdominal
      surgeries and failure to progress. RESULTS: The mean operating time was 329
      minutes but decreased with experience. The median hospital stay was 4 days. Tumor
      stage was directly related to tumor grade. Associated bladder tumors (prior
      history or recurrent tumors) occurred in 50% of the patients. Ipsilateral
      ureteral stump site recurrence occurred in 1 patient. Although no port site
      seeding occurred, 1 patient, whose tumor was discovered histologically after
      laparoscopic pyeloplasty for presumed benign disease, developed recurrence in the
      renal fossa and metastatic disease. Two patients developed liver metastasis.
      CONCLUSIONS: Total laparoscopic and laparoscopic-assisted nephroureterectomy are
      acceptable alternatives to open surgery in the treatment of transitional cell
      carcinoma of the upper urinary tract. Tumor morcellation did not appear to
      adversely affect patient outcome. As with open nephroureterectomy, tumor grade is
      the most important prognostic indicator of local, bladder, and metastatic
      recurrence. No port site seeding was observed in either the total laparoscopic or
      laparoscopic-assisted groups.

PMID- 11248619
TI  - Holmium laser resection of the prostate is more cost effective than transurethral
      resection of the prostate: results of a randomized prospective study.
AB  - OBJECTIVES: A cost-effectiveness analysis was carried out comparing
      electrosurgical transurethral resection of the prostate (TURP) with
      holmium:yttrium-aluminum-garnet laser resection of the prostate (HoLRP). METHODS:
      One hundred twenty patients with benign prostatic hyperplasia and urodynamically
      proved obstruction were randomized to undergo either TURP or HoLRP. Economic and
      clinical outcome data were recorded prospectively out to 1 year postoperatively.
      RESULTS: The HoLRP group experienced fewer complications and had a shorter
      hospital stay and catheterization time than the TURP group, with equivalent
      clinical outcomes at 12 months. HoLRP cost 24.5% less (New Zealand dollars $651)
      than TURP during the first year. CONCLUSIONS: Because the clinical outcomes out
      to 1 year were equivalent, HoLRP was more cost-effective than TURP. On the basis
      of these savings, a minimum of 93 cases per year are required to recover the
      capital and service costs of the holmium:yttrium-aluminum-garnet laser.

PMID- 11248620
TI  - Postvoid residual urine in patients with lower urinary tract symptoms suggestive
      of benign prostatic hyperplasia: pooled analysis of eleven controlled studies
      with alfuzosin.
AB  - OBJECTIVES: A pooled analysis was conducted in patients with lower urinary tract
      symptoms suggestive of benign prostatic hyperplasia to examine the relationship
      between the postvoid residual urine (PVR) volume and various clinical
      characteristics and to assess the effect of alfuzosin, a clinically uroselective
      alpha(1)-blocker, on PVR volume and any other associated outcome. METHODS: Nine
      hundred fifty-three patients, 42 to 89 years old, with a baseline PVR volume
      between 50 and 350 mL (mean 106 mL) were enrolled in 11 double-blind controlled
      studies and received either alfuzosin (n = 607) or placebo (n = 346) for 1 to 6
      months. The relationships between the baseline PVR volume measured by
      transabdominal ultrasound and age, symptoms, maximum flow rate (Qmax), estimated
      bladder capacity, and prostate-specific antigen level were assessed. The changes
      in the PVR volume with treatment were evaluated in all available patients at
      three endpoints (1, 3, and 6 months). RESULTS: At baseline, a PVR volume of 100
      mL or greater was observed in 60%, 47%, and 39% of patients with a Qmax less than
      8, 8 to 11, and greater than 11 mL/s, respectively (P = 0.001). The bladder
      capacity was also significantly related to the Qmax (P = 0.0001). No relationship
      was found between PVR volume and age, symptoms, or prostate-specific antigen
      level. The changes in the PVR volume with treatment were related to the baseline
      PVR volume. However, at all endpoints and whatever the baseline PVR volume, the
      decreases in the PVR volume were significantly (P <0.01) greater with alfuzosin
      than with placebo. Acute urinary retention occurred in 7 patients (2 [0.3%] of
      607 patients taking alfuzosin and 5 [1.4%] of 346 patients taking placebo); 6 of
      these 7 patients had a baseline PVR volume greater than 100 mL. CONCLUSIONS: In
      this population of men with lower urinary tract symptoms suggestive of benign
      prostatic hyperplasia, the PVR olume and bladder capacity were related to the
      baseline Qmax. Alfuzosin significantly reduced the PVR volume compared with
      placebo, and this effect was more marked in patients with a high PVR volume at
      baseline. Acute urinary retention occurred mainly in patients with a PVR volume
      greater than 100 mL and was less frequent in patients taking alfuzosin than in
      those taking placebo.

PMID- 11248621
TI  - Long-term, open-label, phase III multicenter study of tamsulosin in benign
      prostatic hyperplasia.
AB  - OBJECTIVES: To investigate the long-term efficacy and safety of tamsulosin in
      patients with benign prostatic hyperplasia and to monitor the increases and
      decreases in therapeutic response over time. Tamsulosin, a uroselective alpha
      adrenergic receptor antagonist for the treatment of lower urinary tract symptoms
      due to benign prostatic hyperplasia, targets alpha(1A)-adrenergic receptors of
      prostatic smooth muscle with greater affinity than the vascular alpha(1B)
      receptors. Since the alpha(1A)-adrenoceptor subtype mediates prostatic smooth
      muscle tension, alpha(1A)-adrenoceptor antagonists may diminish toxicity, with
      few unwanted effects on blood pressure, while still providing efficacious
      treatment. METHODS: This study extended two 13-week trials and one 40-week
      extension trial for an additional 64 weeks. On study entry, all patients (n =
      949) received 0.4 mg/day tamsulosin. Baseline values were taken from either those
      of the previous trials for patients who had been treated with tamsulosin or the
      first visit of this study for patients not previously exposed to the drug. The
      primary efficacy parameters were the changes in the total American Urological
      Association (AUA) symptom score, mean peak urinary flow rate (Qmax), and
      percentage of patients having 25% or greater improvement in the total AUA symptom
      score and 30% or more improvement in the Qmax. Safety was assessed primarily on
      the incidence and severity of adverse events and discontinuations due to adverse
      events. RESULTS: Improvements from baseline were seen in all primary efficacy
      parameters and were maintained throughout the study. The changes from baseline
      for the total AUA symptom score and Qmax were statistically significant (P
      <0.001) at all 3-month intervals. Tamsulosin was well tolerated, and the
      incidence of adverse events did not increase over time. The mean sitting vital
      signs did not vary from baseline or relative to the treatment duration.
      CONCLUSIONS: Tamsulosin was safe and effective in long-term treatment (longer
      than 1 year) of benign prostatic hyperplasia.

PMID- 11248622
TI  - Levels of insulin-like growth factor I (IGF-I) and IGF binding proteins 2 and 3
      in serial postoperative serum samples and risk of prostate cancer recurrence.
AB  - OBJECTIVES: To determine changes of insulin-like growth factor I (IGF-I), IGF
      binding protein-2 (IGFBP-2), and IGFBP-3 levels in serial postoperative serum
      samples from prostate cancer patients with and without relapse and to evaluate
      the prognostic value of these molecules in the recurrence of prostate cancer.
      METHODS: From a group of patients with prostate cancer who had been followed for
      disease recurrence for almost 5 years after radical prostatectomy, we selected 38
      patients (cases) who developed recurrent disease and 40 patients (controls) who
      were in remission. Of these patients, 70 had 4 and 8 had 3 serial postoperative
      serum samples collected. The median times for serum collection after surgery were
      1.5 years for the first serial samples, 2.6 years for the second, 3.5 years for
      the third, and 4.5 years for the fourth. Serum levels of IGFBP-2, IGFBP-3, and
      IGF-I were measured, using commercial immunoassay kits. RESULTS: The study showed
      lower serum levels of IGFBP-2 and IGFBP-3 in the cases than in controls(P <0.05)
      but no difference in IGF-I levels between the two groups (P = 0.277). In the
      sequential samples, IGFBP-2 levels increased over time in the controls (P =
      0.014) but did not change in the cases (P = 0.528). There were no increasing or
      decreasing trends for IGF-I and IGFBP-3 in either case or control group(P >0.05).
      CONCLUSIONS: The study suggests that IGFBP-2 may play a role in the progression
      of prostate cancer, but serum levels of IGFBP-2 as well as IGF-I and IGFBP-3 have
      no predictive values in the prognosis of prostate cancer.

PMID- 11248623
TI  - Preoperative PSA velocity and doubling time do not predict adverse pathologic
      features or biochemical recurrence after radical prostatectomy.
AB  - OBJECTIVES: To improve the accuracy of predicting pathologic stage and
      biochemical recurrence after radical prostatectomy (RP), we sought to determine
      whether preoperative prostate-specific antigen (PSA) velocity and doubling time
      predict adverse pathologic features or biochemical recurrence following RP. We
      also sought to determine if there were racial differences in preoperative PSA
      velocity and doubling time. METHODS: A total of 331 patients underwent RP at the
      West Los Angeles VA Medical Center between November 1991 and March 2000. Of these
      patients, 86 had two or more preoperative PSA values that were at least 12 months
      apart. Patients were analyzed to determine whether preoperative PSA velocity or
      doubling time was predictive of adverse pathologic features, including positive
      surgical margins, capsular penetration, seminal vesicle invasion, or biochemical
      recurrence. Additionally, PSA velocity and doubling time were compared among
      white, black, Hispanic, and Asian men. RESULTS: Preoperative PSA velocity and
      doubling time were not predictive of positive surgical margins, capsular
      penetration, or seminal vesicle invasion (P >0.30). In addition, there was no
      association between PSA velocity or doubling time and pathologic stage or
      surgical Gleason score (P >0.36). Preoperative PSA velocity (P = 0.581) and
      doubling time (P = 0.528) were not predictors of biochemical recurrence following
      RP. There were no racial differences in preoperative PSA velocity (P = 0.715) or
      doubling time (P = 0.662). CONCLUSIONS: Neither preoperative PSA velocity nor
      doubling time was a predictor of adverse pathologic findings or biochemical
      recurrence after RP. In addition, there was no difference in PSA velocity or
      doubling time between the races studied.

PMID- 11248624
TI  - Artificial neural network model for the assessment of lymph node spread in
      patients with clinically localized prostate cancer.
AB  - OBJECTIVES: To develop an artificial neural network (ANN) model to predict lymph
      node (LN) spread in men with clinically localized prostate cancer and to describe
      a clinically useful method for interpreting the ANN's output scores. METHODS: A
      simple, feed-forward ANN was trained and validated using clinical and pathologic
      data from two institutions (n = 6135 and n = 319). The clinical stage, biopsy
      Gleason sum, and prostate-specific antigen level were the input parameters and
      the presence or absence of LN spread was the output parameter. Patients with
      similar ANN outputs were grouped and assumed to be part of a cohort. The
      prevalence of LN spread for each of these patient cohorts was plotted against the
      range of ANN outputs to create a risk curve. RESULTS: The area under the receiver
      operating characteristic curve for the first and second validation data sets was
      0.81 and 0.77, respectively. At an ANN output cutoff of 0.3, the sensitivity
      achieved for each validation set was 63.8% and 44.4%; the specificity was 81.5%
      and 81.3%; the positive predictive value was 13.6% and 6.5%; and the negative
      predictive value was 98.0% and 98.1%, respectively. The risk curve showed a
      nearly linear increase (best fit R(2) = 0.972) in the prevalence of LN spread
      with increases in raw ANN output. CONCLUSIONS: The ANN's performance on the two
      validation data sets suggests a role for ANNs in the accurate clinical staging of
      patients with prostate cancer. The risk curve provides a clinically useful tool
      that can be used to give patients a realistic assessment of their risk of LN
      spread.

PMID- 11248625
TI  - Significance of high-grade prostatic intraepithelial neoplasia in needle biopsy
      specimens.
AB  - OBJECTIVES: To examine the significance of high-grade prostatic intraepithelial
      neoplasia (HGPIN) in biopsy specimens. METHODS: We performed sextant biopsies on
      a series of 83 cystoprostatectomy specimens removed for bladder cancer. For each
      case the number of foci and volume of both HGPIN and prostate cancer were
      assessed in the prostatectomy specimens and compared with the number of biopsy
      specimens involved by HGPIN. RESULTS: We identified HGPIN in 82 (99%) of 83
      prostatic glands, whereas prostate cancer was found in 41 cases (49%).
      Corresponding sextant biopsies harbored both HGPIN and prostate cancer in 6 cases
      (7%), whereas only HGPIN was diagnosed in 29 sextant biopsies (35%). There was a
      positive correlation between the number of biopsy specimens containing HGPIN and
      the volume and multifocality of HGPIN in the corresponding prostatic glands.
      Prostates with HGPIN on sextant biopsy contained prostate cancer significantly
      more often when compared to cases with no HGPIN on sextant biopsy. Frequency of
      concurrent prostate cancer was higher in cases with two or more biopsy specimens
      containing HGPIN than in cases with only one such biopsy specimen, but case
      numbers of these categories were too small to render this difference
      statistically significant. CONCLUSIONS: The presence of HGPIN in sextant biopsies
      is a significant predictor of concurrent prostate cancer. Multifocality of HGPIN
      is a useful parameter in assessing the extent of HGPIN in the corresponding
      prostates. Its value in predicting a significantly increased risk of concurrent
      prostate cancer needs to be further investigated in larger case studies.

PMID- 11248626
TI  - Efficacy of first-generation Cavermap to verify location and function of
      cavernous nerves during radical prostatectomy: a multi-institutional evaluation
      by experienced surgeons.
AB  - OBJECTIVES: To evaluate, using five experienced surgeons, the efficacy of the
      first-generation Cavermap Surgical Aid to identify the cavernous nerves
      intraoperatively and to predict the recovery of sexual function. This study was
      not designed to determine whether this device improves the ability to preserve
      the nerves or improve outcome. METHODS: Fifty men younger than 60 years old (mean
      age 52.5 years; range 43 to 59) with clinically localized prostate cancer (76%
      T1c, mean Gleason score 6, prostate-specific antigen level less than 10 ng/mL)
      underwent nerve-sparing radical prostatectomy (90% bilateral). Intraoperatively,
      the Cavermap device was used to test for the presence of the cavernous nerves
      once the neurovascular bundle was identified visually and to determine whether
      the nerves were intact after the prostate was removed. Erectile function was
      evaluated using the International Index of Erectile Function; men were considered
      potent if they were able to achieve unassisted intercourse in at least one half
      of their attempts. RESULTS: Before the removal of the prostate, the tumescence
      response to stimulation of the neurovascular bundle was 87.8%; when tissue not
      containing the neurovascular bundle was stimulated, no tumescence response
      occurred in 54%. After prostatectomy, a bilateral response to stimulation
      occurred in 90%, a unilateral response in 5%, and no response in 5%.
      Postoperatively, 71% of the patients were potent at 12 months. In the patients
      who demonstrated bilateral stimulation after removal of the prostate, 78% were
      potent at 12 months. CONCLUSIONS: After radical prostatectomy performed by
      experienced surgeons, patient-reported potency rates in men younger than 60 years
      of age were high. Cavermap stimulation demonstrated an 87.8% sensitivity and 54%
      specificity in locating the neurovascular bundle as identified by experienced
      surgeons. The lack of specificity of this first-generation device limits its
      application for deciding which structures can be safely preserved or excised.
      Because virtually all patients demonstrated a positive response after removal of
      the prostate, the value of stimulation to predict the recovery of sexual function
      is yet to be determined.

PMID- 11248627
TI  - Does urethral-sparing prostatectomy risk residual prostate cancer?
AB  - OBJECTIVES: Urethral length after radical prostatectomy has correlated positively
      with postoperative urinary continence. Because sparing the prostatic urethra may
      improve continence after prostatectomy, we evaluated anatomic and pathologic
      consequences of urethral-sparing surgery. METHODS: From February to October 1999,
      12 patients with clinically localized prostate cancer received a bladder neck
      sparing radical retropubic prostatectomy by one surgeon. At the time of
      operation, the prostatic urethra was anatomically dissected from the
      prostatectomy specimen and sent separately to pathology to evaluate for the
      presence of adenoma or prostate cancer. RESULTS: All patients had clinically
      localized prostate cancer with routine preoperative evaluations, including
      negative bone scans for prostate-specific antigen (PSA) greater than 10 or
      Gleason score higher than 7. Pathologic specimens confirmed localized prostate
      cancer in 7 of 12 specimens. Positive margins were identified in 5, including 2
      patients with locally advanced disease. All 12 urethral specimens showed residual
      prostate adenoma but no prostate cancer. Follow-up ranged from 8 to 16 months
      with a zero PSA for all evaluated. CONCLUSIONS: Residual prostate adenoma is
      found on dissected urethral specimens during radical retropubic prostatectomy.
      Although urethral-sparing prostatectomy may improve continence after radical
      prostatectomy, residual adenoma may confound follow-up PSA results. Furthermore,
      the malignant potential of the benign periurethral adenoma is unknown. The
      patient and clinician must understand the implications of residual prostatic
      tissue when performing urethral-sparing radical retropubic prostatectomy.

PMID- 11248628
TI  - Relationship of first-year costs of treating localized prostate cancer to initial
      choice of therapy and stage at diagnosis: results from the CAPSURE database.
AB  - OBJECTIVES: To determine the relationship among the initial choice of therapy,
      stage at presentation, and first-year treatment costs in men with newly diagnosed
      localized prostate cancer. METHODS: First-year resource use and clinical data
      were collected for 235 subjects with newly diagnosed localized prostate cancer.
      The costs were estimated from the standard Medicare payment schedules. The
      relationship among the initial therapy, stage at presentation, and overall cost
      was examined for the entire cohort and in the subgroup of patients who underwent
      radical prostatectomy. In addition, the inpatient, outpatient, and medication
      cost components were evaluated separately to determine what influenced the
      changes in cost by stage. RESULTS: The mean first-year cost of treating localized
      prostate cancer in CaPSURE was $6375. When broken down by stage, the mean first
      year cost for patients with Stage T1c was $5731, with T2a/b was $6426, and with
      Stage T2c was $6810 (P = 0.059). The initial treatment choice was significantly
      associated with the total first-year costs (P <0.001). The mean cost specifically
      for radical prostatectomy patients with Stage T1c disease was $6881, with T2a/b
      was $7216, and with T2c was $8027 (P = 0.004). The increases in the first-year
      cost with higher stage appeared to primarily be associated with increased
      inpatient resource use and the greater use of adjuvant hormonal therapy.
      CONCLUSIONS: The first-year costs of treating localized prostate cancer in
      CaPSURE are associated with the choice of primary and adjuvant therapy. This
      supports the notion that cost savings may be possible with earlier detection of
      disease or by minimizing the use of hormonal adjuvant therapy.

PMID- 11248629
TI  - Overall and disease-specific survival after radical prostatectomy: geographic
      uniformity.
AB  - OBJECTIVES: To examine whether the survival (both overall and disease-specific)
      of patients who underwent radical prostatectomy varies from region to region in
      the United States. Previous reports have documented a geographic variation in the
      use of radical prostatectomy. METHODS: This study was based on the data from nine
      geographic regions of the Surveillance, Epidemiology, and End Results Program
      (SEER) for 1983 through 1992. Patients with localized prostate cancer who
      underwent radical prostatectomy were included in the analysis. A proportional
      hazards model was used to investigate whether geographic variation is associated
      with both overall and disease-specific survival. RESULTS: From 1983 through 1992,
      the SEER Program collected information from nine geographic regions on 66,293
      patients with localized prostate cancer (mean age 71.8 +/- 8.4 years), who had
      SEER grade codes of 1, 2, or 3. Of these patients, 11,429 (mean age 65.3 +/- 6.5
      years) underwent radical prostatectomy and lymph node dissection. Cox's
      proportional hazards analyses revealed that the impact of geographic location on
      both overall and disease-specific survival in patients who underwent radical
      prostatectomy was not statistically significant. CONCLUSIONS: The results of this
      study indicate that the survival (both overall and disease-specific) of patients
      with localized prostate cancer who underwent radical prostatectomy is not
      influenced by geographic location, suggesting that their survival is relatively
      uniform across the geographic regions in the United States.

PMID- 11248630
TI  - Radiation therapy in non-surgically-treated nonmetastatic prostate cancer:
      geographic and demographic variation.
AB  - OBJECTIVES: To examine the geographic variation in the use of radiation to treat
      nonmetastatic prostate cancer and to identify factors that explain the variation
      in the United States. METHODS: This study was based on data from the nine
      geographic regions of the Surveillance, Epidemiology, and End Results Program for
      1983 through 1996. Patients with localized or regional prostate cancer who did
      not undergo surgical treatment were included in the analysis. Logistic regression
      analysis was used to investigate the influence of geographic and demographic
      factors on the use of radiation. The squared multiple correlation coefficient
      R(2) was used to measure the proportion of variation in the selection of
      radiation explained by each factor of interest. RESULTS: Compared with San
      Francisco, the adjusted odds ratios for 6 of the 8 geographic areas had highly
      significant P values, suggesting the use of radiation therapy varies from region
      to region. However, geographic location only explained less than 3% of the total
      variation in the use of radiation. The geographic location explained a much
      higher proportion of variation in the youngest (younger than 55 years) and the
      oldest (80 years old or older) groups. Overall, age was the most important factor
      that influenced the use of radiation. CONCLUSIONS: The finding that geographic
      location explains a significant proportion of the variation in the use of
      radiation in the youngest and oldest age groups demonstrates the outcome of
      longstanding controversies in the nonsurgical treatment of prostate cancer.
      Documenting the impact of the interaction of age and geographic location on the
      treatment approaches provides for better understanding of the impact of patients
      and physicians making clinical decisions in the management of nonmetastatic
      prostate cancer.

PMID- 11248631
TI  - Five-year retrospective, multi-institutional pooled analysis of cancer-related
      outcomes after cryosurgical ablation of the prostate.
AB  - OBJECTIVES: To define the potential role of cryosurgical ablation of the prostate
      (CSAP) as a treatment option for patients with localized prostate carcinoma
      (PCA), we performed a retrospective outcomes analysis of a large database of
      patients undergoing CSAP constructed from five institutions and compared this
      with matching outcomes from contemporary reports of patient outcomes after
      radiotherapy. METHODS: A total of 975 patients who underwent CSAP as primary
      therapy from January 1993 to January 1998 with sufficient outcomes data available
      were identified. Patients were stratified into three groups on the basis of their
      clinical features. Biochemical-free survival (BFS), post-CSAP biopsy results, and
      post-CSAP morbidities were calculated and recorded. RESULTS: The median follow-up
      for all patients was 24 months. The percentages of patients in the low, medium,
      and high-risk groups were 25%, 34%, and 41%, respectively. For prostate-specific
      antigen thresholds of less than 0.5 and less than 1.0 ng/mL, the 5-year actuarial
      BFS ranged from 36% to 61% and 45% to 76%, respectively, depending on the risk
      category. Overall, the positive biopsy rate was 18%. Morbidities included
      impotence in 93%, incontinence in 7.5%, rectourethral fistula in 0.5%, and
      transurethral resection of the prostate in 13% of patients (10% approved warming
      catheters versus 40% nonapproved). CONCLUSIONS: For each risk group, the 5-year
      BFS and positive biopsy rate after CSAP was comparable to matching outcomes
      reported after radiotherapy. Morbidities also seemed comparable, with impotence
      rates higher and rectal injury rates lower after CSAP than after radiotherapy.
      These data indicate that CSAP can be performed with low morbidity and can produce
      cancer-related results comparable to those reported for patients undergoing
      radiotherapy.

PMID- 11248632
TI  - Relationship between the transition zone index of the prostate gland and urinary
      morbidity after brachytherapy.
AB  - OBJECTIVES: To evaluate whether urinary symptomatology after prostate
      brachytherapy is related to the preimplant transition zone index (TZI =
      transition zone volume/prostate gland volume). METHODS: A total of 170
      consecutive patients without a prior history of transurethral resection of the
      prostate gland (TURP) underwent transperineal ultrasound-guided prostate
      brachytherapy for clinical T1c-T3a carcinoma of the prostate gland. Prostate
      gland and transition zone dimensions and volumes were measured by prolate
      ellipsoid calculation from the static ultrasound images. The relationship between
      TZI and various measures of urinary dysfunction including normalization of
      International Prostate Symptom Scores (IPSS), catheter dependency, the need for a
      subsequent TURP, and the duration of alpha-blocker dependency were evaluated.
      Additional clinical parameters evaluated included the relationship between TZI
      and patient age, clinical T stage, prostate ultrasound volume, neoadjuvant
      hormonal manipulation, and preimplant IPSS. For all indices of urinary
      dysfunction other than serial IPSS, the median patient follow-up was 89.3 weeks.
      The median follow-up for serial IPSS evaluations was 37.3 weeks with a mean of
      11.2 questionnaires per patient. RESULTS: The mean TZI for the 170 patients was
      0.23 +/- 0.06 (prostate gland volume 30.3 +/- 8.7 cm(3), transition zone volume
      7.3 +/- 3.6 cm(3)). The TZI correlated with the time for IPSS normalization, the
      maximum IPSS after brachytherapy, and the maximum increase in IPSS. Conversely,
      the TZI did not correlate with either catheter dependency or alpha-blocker
      dependency. Two of 170 patients (1.2%) required a postimplant TURP. The TZI in
      these 2 patients (0.34) was statistically different (P = 0.016) from the mean.
      CONCLUSIONS: In prostate brachytherapy patients, the preimplant TZI predicted the
      need for a subsequent transurethral resection. The TZI also correlated with
      multiple variants of IPSS. Conversely, TZI did not correlate with either catheter
      dependency or alpha-blocker dependency.

PMID- 11248634
TI  - Return of spontaneous erection during long-term intracavernosal alprostadil
      (Caverject) treatment.
AB  - OBJECTIVES: To investigate the effect of long-term intracavernosal self-injection
      of alprostadil (Caverject) on the penile circulation and return of spontaneous
      erection in men with arteriogenic erectile dysfunction. METHODS: Seventy men with
      a stable heterosexual partner entered the titration phase of this open-label,
      flexible-dose study. The effective alprostadil dose (ie, the dose producing
      penile rigidity adequate for intercourse and lasting up to 60 minutes) was
      determined before entry into the 12-month self-treatment home phase. Duplex
      ultrasonography was used to measure the peak systolic velocity and diameter of
      the cavernosal arteries at the end of the titration phase and after 4, 8, and 12
      months of the home phase. The efficacy, tolerability, and return of spontaneous
      erections were assessed from the patients' diaries and by interview at each
      clinic visit. Sixty-three men entered the home phase; 49 of them filled out the
      diaries and 42 completed the study. RESULTS: An effective dose was established
      for 67 (96%) of the 70 men (median dose 15 microg). During the home phase, 94% of
      men responded to alprostadil, and the median dose remained unchanged. Complete
      duplex ultrasound data were obtained in 38 men and showed significant increases
      in postinjection peak systolic velocity in both cavernosal arteries (P <0.001 at
      12 months) and between the preinjection and postinjection cavernosal arterial
      diameters (P = 0.0001) compared with baseline. Reports of a return of spontaneous
      erections increased throughout the study compared with baseline (37%, 26 of 70)
      and were confirmed by interview for 46 (85%) of 54 men with available data
      overall. Treatment was generally well accepted, with low incidences of penile
      pain (23%), prolonged erection, which resolved spontaneously (6%), and fibrosis
      (1%). CONCLUSIONS: Intracavernosal alprostadil was effective, acceptable, and
      generally well tolerated in men with arteriogenic erectile dysfunction. Long-term
      treatment improved the penile circulation, and most men reported an increase in
      return of spontaneous erections.

PMID- 11248633
TI  - Response to varicocelectomy in oligospermic men with and without defined genetic
      infertility.
AB  - OBJECTIVES: To compare the clinical characteristics of infertile men who have
      varicocele with and without a genetic anomaly, and report the results of
      varicocelectomy in these two cohorts of men. METHODS: Study subjects included 33
      men who underwent genetic counseling and testing for a diagnosis of oligospermia
      with varicocele. Seven men were diagnosed with coexisting genetic infertility
      (genetic [+]; abnormal karyotype in 4, Y chromosome microdeletion in 3), and 26
      men with varicocele and no genetic abnormality (genetic [-]). Five patients (Y
      chromosome microdeletions in 2, abnormal karyotype in 3) in the genetic (+) group
      and 14 patients in the genetic (-) group underwent microsurgical subinguinal
      varicocelectomy. Semen and hormonal parameters, physical examination findings, as
      well as the response to varicocele repair were compared between the two groups.
      Varicocele response was defined as a 50% increase in total motile sperm count in
      the ejaculate. RESULTS: Mean preoperative seminal and hormonal parameters were
      not statistically significantly different between the two groups. Significant
      differences were observed in the volume of the right and left testicles between
      the two groups (left: P = 0.007; right: P = 0.04). Although 7 of 13 evaluable
      patients (54%) in the genetic (-) group had a seminal response to
      varicocelectomy, none of 5 patients in the genetic (+) group showed improvement
      in semen quality. CONCLUSIONS: From this early experience, men with varicocele
      and genetic lesions appear to have a poorer response to varicocele repair than
      men without coexisting genetic lesions. These data may have implications for
      counseling male factor infertility patients contemplating varicocele treatment.

PMID- 11248635
TI  - Ureteropelvic junction obstruction and coexisting renal calculi in children: role
      of metabolic abnormalities.
AB  - OBJECTIVES: To identify the role of metabolic risk factors in the development of
      renal calculi associated with ureteropelvic junction obstruction (UPJO) in
      children. METHODS: A metabolic evaluation, including serum biochemistry and
      measurement of daily urinary calcium, creatinine, oxalate, citrate, magnesium,
      urate, and inorganic phosphorus, was carried out in three different populations
      as follows: UPJO group, 12 children with UPJO and coexisting nephrolithiasis
      (median age 6 years); calcium stone formation (CSF) group, 90 children with
      normal urologic anatomy and calcium urolithiasis (median age 7 years); control
      group, 24 healthy children (median age 7.3 years). The investigation data of the
      three groups were compared. RESULTS: The stone composition was calcium oxalate in
      9 of the 12 children with UPJO. The investigation data of the UPJO group and CSF
      group were not significantly different. Both groups differed from the control
      group in a similar manner. The UPJO and CSF groups excreted more oxalate (P =
      0.067 and 0.014, respectively) and less citrate (P = 0.020 and 0.010,
      respectively) than did the control subjects. CONCLUSIONS: Abnormal urinary
      biochemistry seems to have an additional role in the high incidence of
      nephrolithiasis in children with upper tract anatomic anomalies, and the urinary
      biochemistry should be screened in such children.

PMID- 11248639
TI  - Technique of parastomal hernia repair using synthetic mesh.
AB  - We describe a reliable and simple technique of parastomal hernia repair using
      primary fascial repair with synthetic mesh that minimizes the known complications
      of infection and stomal stenosis while eliminating the need for peritoneal
      exploration, lysis of adhesions, and relocation of the stoma. We applied this
      technique to 6 patients (aged 65 to 83 years) with symptomatic, first-time
      parastomal hernias. The results are discussed.

PMID- 11248637
TI  - Percutaneous nephrostomy in children with ureteropelvic junction obstruction and
      poor renal function.
AB  - OBJECTIVES: To evaluate the results of performing percutaneous nephrostomy (PCN)
      in all patients with kidneys with ureteropelvic junction obstruction (UPJO) and
      split renal function (SRF) of less than 10%, because the management of such cases
      is still under debate. If SRF improves, we perform pyeloplasty, otherwise
      nephrectomy is done. METHODS: The records of all patients with UPJO (n = 20; 17
      unilateral and 3 solitary kidney) with poor function who underwent PCN were
      analyzed. The PCN remained in situ for at least 4 weeks, during which patients
      received low-dose oral trimethoprim prophylaxis. Repeated renography was obtained
      after 4 weeks. If no improvement in the SRF had occurred, nephrectomy was
      performed, otherwise pyeloplasty was performed. The patients were followed up
      with renograms at 3 months, 1 year, 2 years, and 5 years. RESULTS: Twelve of 17
      kidneys with unilateral UPJO improved after PCN drainage and underwent
      pyeloplasty. The 5 kidneys that did not show improvement in the SRF underwent
      nephrectomy. In the patients with unilateral UPJO who improved after PCN
      drainage, the SRF increased to 29.2% +/- 12.6% and pyeloplasty was performed. At
      a mean follow-up of 2.3 years, none of these patients had developed hypertension,
      and the most recent SRF value was 31.4% +/- 12.8%. CONCLUSIONS: Most of the
      poorly functioning UPJO kidneys show improvement in function and not all such
      kidneys should be removed without a trial of PCN.

PMID- 11248640
TI  - Prostatic abscess in the newborn: an unrecognized source of urosepsis.
AB  - We present a 10-day-old boy who developed fulminant urosepsis. At autopsy, he was
      found to have a prostatic abscess as his sole source of infection. We reviewed
      the 12 previous reported cases of prostatic abscess in newborns and present
      factors that may suggest the diagnosis. The treatment and outcome in each of the
      cases are also presented.

PMID- 11248641
TI  - Primary carcinoid of the testis 25 years after contralateral testicular seminoma.
AB  - We report a case of primary testicular carcinoid occurring coincidentally 25
      years after contralateral radical orchiectomy for seminoma, which has not been
      previously reported.

PMID- 11248642
TI  - Nephrolithiasis during pregnancy secondary to primary hyperparathyroidism.
AB  - Nephrolithiasis secondary to primary hyperparathyroidism infrequently complicates
      pregnancy. It can cause severe maternal and fetal complications. We present a
      case of a pregnant woman with nephrolithiasis and primary hyperparathyroidism. We
      reviewed the management of nephrolithiasis due to primary hyperparathyroidism
      during pregnancy. We believe that early recognition and timely intervention can
      significantly reduce the incidence of complications.

PMID- 11248643
TI  - Giant bilateral renal angiomyolipomas associated with tuberous sclerosis.
AB  - Renal angiomyolipomas in patients with tuberous sclerosis can be associated with
      significant morbidity, mostly related to complications from bleeding. We describe
      a patient with tuberous sclerosis and massive bilateral renal angiomyolipomas
      (total tumor burden 5500 g) who presented with acute right renal hemorrhage. She
      was treated with right renal artery embolization followed immediately by right
      nephrectomy and left partial nephrectomy. The patient had a creatinine nadir of
      1.3 mg/dL postoperatively. We demonstrate that nephron-sparing surgery is
      feasible, even in the setting of very large angiomyolipomas, such as the one
      presented here, currently the largest such tumor by weight reported.

PMID- 11248644
TI  - Laparoscopic gonadectomy and excision of mullerian remnant in an adult intersex
      patient.
AB  - Laparoscopy can assist in the diagnosis and treatment of intersex patients. We
      report a rare case in which laparoscopic gonadectomy and hysterosalpingectomy
      were performed in a phenotypically-male intersex patient first diagnosed in
      adulthood.

PMID- 11248645
TI  - Ureterocele prolapse-rare presentation in an adolescent girl.
AB  - Ureterocele prolapse is a rare presentation of single system ureteroceles and is
      usually found early in childhood. We present a rare case of recurrent prolapse of
      a single system ureterocele that did not present until the patient was 17 years
      of age.

PMID- 11248646
TI  - Bilateral testicular lymphoma treated with chemotherapy and radiation without
      orchiectomy: complete response relapsed at 52 months in the vitreous humor.
AB  - We report the first detailed case of testicular lymphoma managed with
      chemotherapy and radiation without orchiectomy. A 60-year-old man with Stage II
      extralymphatic bilateral testicular lymphoma refused orchiectomy, but underwent
      cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy and
      radiation. He remained disease free for 52 months, when a solitary central
      nervous system relapse to the vitreous humor was diagnosed. The optimal therapy
      for testicular lymphoma is unclear but often includes orchiectomy with adjuvant
      chemotherapy and radiation. Stage I testicular lymphoma can be cured by surgery
      alone; however, the relapse rates for all stages of testicular lymphoma are high
      despite systemic therapy. For Stage II disease and higher, chemotherapy/radiation
      is recommended; orchiectomy may not be mandatory.

PMID- 11248647
TI  - Secretory IGA differentially promotes adherence of type 1-piliated Escherichia
      coli to immortalized vaginal epithelial cell lines.
AB  - OBJECTIVES: To elucidate the factors that influence bacterial adherence to
      vaginal epithelium. We developed an in vitro model to examine the interaction of
      type 1-piliated Escherichia coli, strain HB101/p1-17, with immortalized vaginal
      epithelial cells (VEC) from postmenopausal donors with (patient 1) and without
      (patient 2) clinical histories of urinary tract infections (UTI). METHODS: The
      VEC were incubated in microtiter plates in the presence of E. coli HB101/p1-17,
      and factors such as time, mannose concentration, and secretory immunoglobulin A
      (sIgA) concentration were assessed. After incubation, the numbers of bacteria
      bound per VEC were counted on a scintillation counter. RESULTS: The E. coli
      adhered to the VEC and the adherence was inhibited in the presence of 100-mM
      mannose solution. Clinical donor UTI histories were reflected in the binding
      characteristics of the VEC cell lines, with cells from patient 1 having a 30%
      higher baseline binding capacity than cells from patient 2 and an enhanced
      binding response in the presence of increasing sIgA concentrations. The sIgA
      concentration did not affect the patient 2 cell-bacterial binding. CONCLUSIONS:
      These results indicate that our in vitro model is suitable for studying the
      factors influencing bacterial adherence to vaginal mucosa, and that after
      immortalization, vaginal mucosa maintains clinically relevant characteristics
      that can be studied. Our data suggest that E. coli adherence to vaginal mucosa
      from postmenopausal women susceptible to UTI is affected by intrinsic baseline
      bacterial binding capacity of the mucosa cells as well as by increased sIgA
      concentration in the women's vaginal fluid. Increasing vaginal fluid sIgA
      concentration in this population may have a deleterious rather than beneficial
      effect.

PMID- 11248648
TI  - Hemostatic laparoscopic partial nephrectomy: cable-tie compression.
AB  - OBJECTIVES: Laparoscopic partial nephrectomy (LPN) has generally been reserved
      for small exophytic lesions because of the limited hemostatic capabilities when
      excising large segments of renal parenchyma. To overcome this problem, we
      investigated a technique of laparoscopic reversible, regional hypoperfusion using
      a cable-tie to minimize blood loss and optimize exposure. METHODS: Ten domestic
      pigs underwent LPN after securing a cable-tie around one pole of the kidney and
      tightening it until the distal parenchymal surface blanched completely. Eight
      large amputations involving the collecting system and eight smaller amputations
      excluding the collecting system were performed using laparoscopic scissors.
      Fibrin glue was applied to seal the cut surface prior to cable-tie removal. Four
      pigs (4 large and 4 small amputations) were killed immediately and methylene blue
      was injected retrograde into the ureter to identify collecting system leaks. The
      remaining 6 pigs (4 large and 4 small amputations) were killed 4 weeks later and
      retrograde urograms were performed to assess collecting system integrity.
      RESULTS: Median cable-tie ischemia time was 15 minutes (range 7 to 48) and median
      blood loss was 30 mL (range 10 to 300). In each case, hemostasis was attained
      with fibrin glue. In the survival group, all 4 small amputations healed with a
      fibrotic scar. In the large amputation group, 1 animal died from urinary
      extravasation on postoperative day 4. The collecting systems of the remaining 3
      pigs sealed completely. CONCLUSIONS: In the porcine model, cable-tie-assisted LPN
      provides an almost bloodless surgical field that facilitates rapid resection of
      large renal segments and hemostasis during a short ischemic period. We anticipate
      that this technique will broaden the clinical application of LPN.

PMID- 11248650
TI  - CD40 is not detected on human prostate cancer cells by immunohistologic
      techniques.
AB  - OBJECTIVES: The CD40 antigen is expressed by antigen-presenting cells, many kinds
      of epithelium, and carcinomas. As signaling through CD40 modulates the
      differentiation state of CD40-expressing cells, we wanted to investigate whether
      benign or malignant prostate epithelium expressed CD40. METHODS: Twenty-two
      paraffin-embedded and 10 snap-frozen human prostate tissue samples were analyzed
      by immunohistologic methods, using the basal cell-specific markers, high
      molecular weight cytokeratin (HMWCK) and keratin-14 (K14), and the luminal cell
      marker, low molecular weight cytokeratin (LMWCK), together with CD40. Fresh
      prostate tissue was cultured in vitro and analyzed by immunocytofluorescence.
      RESULTS: The pattern of CD40 expression was continuous on basal epithelial cells
      of normal and hyperplastic prostate glands but discontinuous in glands that
      featured prostatic intraepithelial neoplasia. Coexpression of CD40 with the basal
      cell-specific cytokeratins, HMWCK and K14, was confirmed by double labeling. In
      contrast, glandular epithelial cells in prostate adenocarcinoma did not express
      CD40 or these cytokeratins. A luminal cell phenotype defined as CAM5.2-positive
      and HMWCK-negative K14-negative was identified among primary epithelial cells
      cultured in vitro. Most of the cultured cells (more than 99%) were also CD40
      negative. CONCLUSIONS: Together, our results support the hypothesis that CD40
      expression correlates with the basal cell phenotype, which is lost upon malignant
      transformation of the prostate. Hence, CD40 may be useful diagnostically to
      distinguish benign from malignant prostate lesions in biopsy material.

PMID- 11248649
TI  - Association of vitamin D receptor and 17 hydroxylase gene polymorphisms with
      benign prostatic hyperplasia and benign prostatic enlargement.
AB  - OBJECTIVES: To determine whether polymorphisms in 17 hydroxylase (CYP17) and
      vitamin D receptor (VDR) genes have an association to prostate volume/histology
      and endocrine patterns in elderly men with lower urinary tract symptoms (LUTS).
      METHODS: Elderly men with LUTS underwent the following investigations:
      International Prostate Symptom Score (IPSS), uroflowmetry, serum prostate
      specific antigen (PSA) assessment of prostate volume, and an endocrine study.
      Polymorphisms of CYP17 (T-->C substitution in the 5' promoter region) and VDR
      (T1055C) genes were detected by polymerase chain reaction followed by restriction
      length polymorphism analysis, using DNA from peripheral white blood cells.
      Clinical and endocrine parameters and the prostate stroma/epithelial ratio were
      correlated to CYP17 and VDR genotypes. RESULTS: A total of 148 (mean +/- SD, 67.0
      +/- 9.7 years) patients were analyzed. IPSS (17.8 +/- 7.0), prostate volume (41.9
      +/- 17.9 cc), maximum flow rate (10.9 +/- 5.8 mL/s), and PSA (4.7 +/- 4.7 ng/mL)
      indicate a typical LUTS population. Mean endocrine levels were consistently
      within age-specific reference values. Neither CYP17 nor VDR gene polymorphisms
      revealed an association to prostate size, PSA, clinical parameters, and endocrine
      parameters. Men who had the A1/A1 CYP17 genotype had on average a greater
      stromal/epithelial ratio than men with the A1/A2 or A2/A2 genotypes, yet after
      adjusting for multiple testing, this significance disappeared. CONCLUSIONS: Gene
      polymorphisms of CYP17 and VDR have no association to prostate volume, clinical
      parameters, and endocrine parameters in elderly men. The association of CYP17
      polymorphism and prostate histology warrants further studies. Assessment of gene
      polymorphisms might provide new insights into the pathogenesis of benign
      prostatic hyperplasia and benign prostate enlargement and may hold promise as
      genetic biomarkers of this disease.

PMID- 11248651
TI  - Preferential gene transfer to BBN-induced rat bladder tumor by simple
      instillation of adenoviral vector.
AB  - OBJECTIVES: We examined the efficacy and safety of intravesical instillation of
      adenoviral vectors to develop gene therapy protocols for bladder cancer. In this
      study, an adenoviral vector containing the beta-galactosidase gene was instilled
      into the rat bladder with N-butyl-N-(4-hydroxybutyl) nitrosamine-induced tumors.
      We evaluated the effect of the glycosaminoglycan (GAG) layer on adenoviral
      transduction of bladder urothelium. In addition, we determined the systemic
      distribution of the adenoviral vector after instillation. METHODS: An adenoviral
      vector containing either the beta-galactosidase or the herpes simplex virus
      thymidine kinase gene was transurethrally instilled into the bladder, after which
      efficacy of gene transfer was evaluated by staining with 5-bromo-4-chloro-3
      indolyl-beta-D-galactopyraminoside, and the distribution of the gene was examined
      by reverse transcriptase-polymerase chain reaction. To determine the extent to
      which the GAG layer may have inhibited gene transfer by the adenoviral vector,
      prior to instillation of adenoviral vector, normal bladders were pretreated with
      either phosphate-buffered saline or HCl, which would destroy the mucosal GAG
      layer. RESULTS: We found that intravesical instillation of an adenoviral vector
      caused preferential gene transfer to the tumor cells and that expression of the
      transferred gene occurred exclusively in the bladder. Removing the GAG layer
      rendered the normal bladder highly susceptible to adenoviral gene transfer,
      indicating that GAG on normal mucosa prevented adenoviral gene transfer.
      CONCLUSIONS: BBN-induced bladder tumors were preferentially transduced by
      instillation of adenoviral vectors probably due to the lack of GAG layers on
      their surface. Intravesical instillation of adenoviral vectors does not result in
      systemic infection. These results encourage the consideration of gene therapy in
      the treatment of human bladder cancer.

PMID- 11248652
TI  - Combination of phentolamine and L-arginine or sildenafil synergistically improves
      neurogenic relaxation of rabbit corpus cavernosum smooth muscle.
AB  - OBJECTIVES: To analyze the effects of combining an alpha-adrenergic receptor
      antagonist, phentolamine, with an enhancer of the nitric oxide/cyclic guanosine
      monophosphate pathway (L-arginine or sildenafil) on neurogenic relaxations of
      rabbit corpus cavernosum (RCC). METHODS: Studies were performed on isolated RCC
      tissue in organ chambers. Transmural electrical stimulation (TES) was applied at
      increasing frequencies (0.5 to 6 Hz) on endothelin-contracted RCC strips, and the
      responses were evaluated. RESULTS: The activation of alpha(2)-adrenergic
      receptors with UK 14304 (0.3 microM) significantly inhibited the relaxation
      induced by TES in RCC strips in which adrenergic neurotransmission was blocked
      with guanethidine (10 microM). The relaxant responses produced by TES application
      on RCC strips without guanethidine were not significantly affected by the
      treatment with L-arginine or sildenafil but were significantly augmented by
      phentolamine (2.7-fold increase in maximum relaxation). Furthermore, the
      combinations of phentolamine with L-arginine or sildenafil markedly increased the
      relaxations evoked by the application of TES in RCC tissue, significantly more
      than those obtained in the presence of phentolamine alone (4.5 or 4.7-fold
      increase of maximum relaxation, respectively). CONCLUSIONS: Our results
      demonstrated a synergistic interaction between the alpha-adrenergic blockade and
      the potentiation of the nitric oxide/cyclic guanosine monophosphate pathway to
      increase neurogenic relaxation of trabecular smooth muscle relaxation. This fact
      suggests that the combination of alpha-adrenergic receptor blockade with L
      arginine or sildenafil could represent a therapeutic advantage in the treatment
      of erectile dysfunction.

PMID- 11248653
TI  - Bone tissue and its mineralization in aged estrogen-depleted rats after long-term
      intermittent treatment with parathyroid hormone (PTH) analog SDZ PTS 893 or human
      PTH(1-34).
AB  - Intermittently administered parathyroid hormone (PTH) is a potent bone anabolic
      agent. We aimed to determine the impact of long-term treatment with PTH on bone
      structure, dynamics, and mineralization. We ovariectomized (ovx) 1-year-old rats
      with the exception of a baseline and a sham-operated group. Twelve weeks later, a
      36 week treatment with PTH analog SDZ PTS 893 (12.5, 25, 50, 100 microg/kg),
      human PTH(1-34) (25, 50, 100 microg/kg), or vehicle (ovx, sham) was initiated.
      Bone dynamics, structure, and mineralization were evaluated in the lumbar spine
      and in the femoral diaphysis. Cancellous bone turnover was elevated 12 weeks
      postovariectomy in estrogen-deficient, vehicle-treated animals, but returned to
      the level of the sham group by 48 weeks. The animals experienced substantial
      cancellous bone loss associated with a reduction of trabecular number and
      presented with a partly rod-like trabecular network. After 36 weeks of treatment
      with SDZ PTS 893 or human PTH(1-34), cancellous bone formation rates and turnover
      were raised in all treated groups compared with age-matched controls. The mineral
      apposition rate was increasing with dose. This amplified matrix synthesis led to
      trabecular thickening, but not to an increase in trabecular number, resulting in
      a crude, plate-like cancellous network with a high bone volume fraction.
      Fluorochrome label-based cortical bone dynamics demonstrated that a thick ring of
      new bone was formed at the endocortex by activation of modeling drifts during
      treatment. Treatment-induced cortical bone formation was increased with dose at
      the subperiosteal and endocortical envelopes, but substantially higher at the
      latter. Intracortical bone turnover was elevated near the endocortex. Bone
      mineralization was undisturbed in all compartments. The average degree of
      mineralization was lowered slightly, reflecting the increased portion of new bone
      formed during treatment. In summary, the main anabolic effect was mediated for
      both peptides by an increase in bone apposition with dose, persisting throughout
      treatment that lasted more than one third of the lifespan of the rats, and direct
      activation of bone-forming surfaces. As a result, a substantial amount of new
      bone, maintained at elevated turnover and adequate mineralization levels, formed
      predominantly at compartments exposed to bone marrow.

PMID- 11248654
TI  - Maintenance of cortical bone in human parathyroid hormone(1-84)-treated
      ovariectomized rats.
AB  - The purpose of this cross-sectional study was to evaluate the effects of human
      parathyroid hormone(1-84) (hPTH) followed by maintenance treatment with 17beta
      estradiol (E(2)), risedronate (Ris), or a reduced dose of hPTH (LowPTH) on
      cortical bone in the ovariectomized (ovx) rat. Eight groups of ovx and one group
      of intact female rats (3.5 months) were left untreated for 11 weeks. For the
      following 12 weeks, four groups received subcutaneous injections of hPTH (75
      microg/kg per day on 3 days/week) and four groups received vehicle. Treatments
      were then changed to E(2) (10 microg/kg per day on 2 days/week), Ris (3 microg/kg
      per day on 3 days/week), LowPTH (25 microg/kg per day on 3 days/week), or
      vehicle. Bone tissue was collected at weeks -11 (baseline), 0 (ovx effect), 12
      (hPTH effect), 24, 36, and 48 (maintenance effect). Bone mineral density (BMD)
      and bone mineral content (BMC) of the diaphyseal femur and total cross-sectional
      area (Tt.Ar), marrow area (Ma.Ar), cortical area (Ct.Ar), and periosteal and
      endocortical bone formation of the tibia were measured. Ovariectomy resulted in
      lower BMD (weeks 0-48), unaffected BMC, and greater Tt.Ar (weeks 12 and 36),
      Ma.Ar (week 48), and Ct.Ar (weeks 0 and 12) compared with intact rats.
      Endocortical and periosteal bone formation were greater in the ovx than in the
      intact rats up to 23 weeks postovariectomy. Treatment of ovx rats with hPTH for
      12 weeks resulted in greater cortical BMD, BMC, and endocortical bone formation
      than in intact or ovx controls. In ovx rats pretreated with hPTH and then treated
      with Ris for 36 weeks, BMD and BMC were greater and Ma.Ar was smaller than in ovx
      controls. In ovx rats pretreated with hPTH and then treated with LowPTH, BMD,
      BMC, Ct.Ar, and endocortical bone formation were greater and Ma.Ar was smaller
      than in ovx controls. Treatment of hPTH-pretreated rats with E(2) for 36 weeks
      did not affect cortical BMD, BMC, and Ct.Ar, although periosteal bone formation
      was lower in the E(2) group compared with the ovx group. Thus, in ovariectomized
      rats, cortical bone gained by 12 weeks of hPTH treatment was maintained for up to
      36 weeks by treatment with risedronate or low-dose hPTH, but not with 17beta
      estradiol.

PMID- 11248655
TI  - The effect of macrophage-colony stimulating factor and other humoral factors
      (interleukin-1, -3, -6, and -11, tumor necrosis factor-alpha, and granulocyte
      macrophage-colony stimulating factor) on human osteoclast formation from
      circulating cells.
AB  - Macrophage-colony stimulating factor (M-CSF) is an essential requirement for
      human osteoclast formation, but its effect on the proliferation and
      differentiation of circulating osteoclast precursor cells is unknown. Other
      growth factors and cytokines are also known to support/stimulate osteoclast
      formation from mouse marrow precursors, but it is not certain whether these
      factors similarly influence human osteoclast formation. In this study, human
      monocytes were cocultured with osteoblast-like UMR-106 cells on coverslips and
      dentine slices for up to 21 days in the presence of 1,25 dihydroxyvitamin D(3)
      (10(-7) mol/L), dexamethasone (10(-8) mol/L), and various concentrations of
      either M-CSF or other humoral factors (interleukin [IL]-1beta, IL-3, IL-6, and IL
      11; tumor necrosis factor-alpha [TNF-alpha]; and granulocyte macrophage [GM]
      CSF). The effect on osteoclast formation was assessed by tartrate-resistant acid
      phosphatase (TRAP) and vitronectin receptor staining and lacunar bone resorption.
      The results of time-course and proliferation studies showed that M-CSF stimulated
      both the proliferative and differentiation stages of human osteoclast formation
      from circulating osteoclast precursors in a dose-dependent manner. A high
      concentration of M-CSF (100 ng/mL) did not inhibit osteoclast formation. IL-3 and
      GM-CSF were also capable of stimulating human osteoclast formation, although
      these growth factors were much less potent than M-CSF. IL-3- and GM-CSF
      stimulated osteoclast formation was inhibited by an antibody specific for human M
      CSF. Osteoclast formation and lacunar resorption was not seen when either TNF
      alpha, IL-1beta, IL-6 (+ soluble IL-6 receptor), or IL-11 was substituted for M
      CSF during coculture. These results confirm that M-CSF is essential for human
      osteoclast formation from circulating mononuclear precursors, and also shows that
      IL-3 and GM-CSF may support osteoclast differentiation via the stimulation of M
      CSF production by human monocytes.

PMID- 11248656
TI  - Interleukin (IL)-13 and IL-4 inhibit proliferation and stimulate IL-6 formation
      in human osteoblasts: evidence for involvement of receptor subunits IL-13R, IL
      13Ralpha, and IL-4Ralpha.
AB  - Interleukin-13 (IL-13) inhibits cell proliferation and stimulates interleukin-6
      (IL-6) formation in isolated human osteoblasts (hOBs). Because the related
      cytokine, interleukin-4 (IL-4), is known to exert effects similar to IL-13 in
      other tissues, and because IL-4 has been implicated as a regulator of bone
      metabolism, we compared the effects of IL-13 and IL-4 on cell proliferation, IL-6
      synthesis, the expression of osteoblastic phenotypic markers in hOB cultures.
      Also, the receptor proteins mediating these effects in hOBs have been partly
      characterized. IL-4 and IL-13 dose-dependently inhibited [(3)H]-thymidine
      incorporation into the DNA of human osteoblasts and stimulated secretion of IL-6
      into culture supernatants. IL-13 and IL-4 also increased the mRNA levels of IL-6,
      as measured by RNAse protection assay. Furthermore, IL-13 and IL-4 dose
      dependently enhanced alkaline phosphatase (ALP) activity, but did not affect
      osteocalcin or collagen type I synthesis. IL-4 was tenfold more potent than IL-13
      in inducing both ALP activity and IL-6 secretion, whereas the cytokines were
      equipotent as inhibitors of cell proliferation. The expression of mRNA for
      receptor subunits previously implicated in IL-4 and IL-13 signaling was
      investigated by reverse transcriptase-polymerase chain reaction. IL-13R, IL
      13Ralpha, and IL-4Ralpha mRNA were repeatedly detected in hOBs, whereas mRNA for
      IL-2Rgamma(C) was not detected. Receptor-blocking antibodies to IL-4Ralpha
      inhibited the induction of IL-6 formation by both IL-4 and IL-13, indicating that
      both cytokines utilize this receptor subunit in signaling. However, the
      antibodies did not affect the IL-4/-13-induced inhibition of [(3)H]-thymidine
      incorporation or the stimulation of alkaline phosphatase (ALP), suggesting that
      IL-4Ralpha does not mediate these effects of IL-4/-13 in hOBs. We conclude that
      the cytokines IL-13 and IL-4, through sharing of receptor components, induce
      similar effects on hOBs, causing inhibition of cell proliferation, stimulation of
      IL-6, and enhanced ALP activity.

PMID- 11248657
TI  - Expression of the prostaglandin E(2) (PGE(2)) receptor subtype EP(4) and its
      regulation by PGE(2) in osteoblastic cell lines and adult rat bone tissue.
AB  - Prostaglandins E (especially PGE(2)) stimulate bone formation and increase bone
      mass in several species including man. The mechanism for this effect, the target
      cells, and the receptors involved are not known. Specific cell-surface receptors
      for PGE(2) (EP(1-4)) have been cloned and characterized. EP(4) was reported to be
      the major receptor in embryonic and neonatal bone tissue in mice, especially in
      preosteoblasts; however, no data are available regarding its expression in adult
      bone. This study examines the expression of EP(4) in bone tissue of young adult
      rats, in which PGE(2) is markedly anabolic, and in various osteoblastic cell
      lines. Using northern blot analysis, we found that osteoblastic cell lines RCT-1,
      RCT-3, TRAB-11, and RP-1, primary osteoblastic cells harvested from fetal rat
      calvaria, as well as tibiae and calvariae of 5-week-old rats express 3.8 kb EP(4)
      messenger RNA (mRNA). Treatment of periosteal cells (RP-1) in vitro with 10(-6)
      mol/L PGE(2) increased the levels of both EP(4) mRNA and EP(4) protein, peaking
      at 1-2 h. Similarly, systemic administration of an anabolic dose of PGE(2) (3-6
      mg/kg) to young adult rats upregulated the expression of EP(4) in the tibia and
      calvaria, also peaking at 1-2 h. Using in situ hybridization, we found increased
      expression of EP(4) in bone marrow cells of the tibial metaphysis in response to
      systemic PGE(2) treatment. The preosteoblastic nature of these EP(4)-expressing
      cells was suggested by the fact that dexamethasone-treated bone marrow stromal
      cells in culture express EP(4) mRNA, which is upregulated by PGE(2). Northern
      blot analysis failed to detect both basal and PGE(2)-induced EP(2) mRNA in the
      bone samples or cell lines tested. Taken together, these data implicate EP(4) as
      the major cyclic AMP-related PGE(2) receptor subtype expressed in bone tissue and
      osteoblastic cells and indicate that this receptor is upregulated by its ligand,
      PGE(2).

PMID- 11248658
TI  - Biosynthesis and processing of cathepsin K in cultured human osteoclasts.
AB  - Cathepsin K (cat K) is the major cysteine protease expressed in osteoclasts and
      is thought to play a key role in matrix degradation during bone resorption.
      However, little is known regarding the synthesis, activation, or turnover of the
      endogenous enzyme in osteoclasts. In this study, we show that mature cat K
      protein and enzyme activity are localized within osteoclasts. Pulse-chase
      experiments revealed that, following the synthesis of pro cat K, intracellular
      conversion to the mature enzyme occurred in a time-dependent manner.
      Subsequently, the level of mature enzyme decreased. Little or no cat K was
      observed in the culture media at any timepoint. Pretreatment of osteoclasts with
      either chloroquine or monensin resulted in complete inhibition of the processing
      of newly synthesized cat K. In addition, pro cat K demonstrated susceptibility to
      treatment with N-glycosidase F, suggesting the presence of high-mannose
      containing oligosaccharides. Treatment of osteoclasts with the PI3-kinase
      inhibitor, Wortmannin (WT), not only prevented the intracellular processing of
      cat K but also resulted in the secretion of proenzyme into the culture media.
      Taken together, these results suggest that the biosynthesis, processing, and
      turnover of cat K in human osteoclasts is constitutive and occurs in a manner
      similar to that of other known cysteine proteases. Furthermore, cat K is not
      secreted as a proenzyme, but is processed intracellularly, presumably in
      lysosomal compartments prior to the release of active enzyme into the resorption
      lacunae.

PMID- 11248659
TI  - Enhancement of bone morphogenetic protein-2-induced new bone formation in mice by
      the phosphodiesterase inhibitor pentoxifylline.
AB  - Porous collagen disks (6 mm diameter, 1 mm thickness) were impregnated with
      recombinant human bone morphogenetic protein-2 (rhBMP-2) (5 microg/disk) and
      implanted onto the back muscles of mice. Pentoxifylline (PTX), which is a
      methylxanthine-derived inhibitor of phosphodiesterases (PDEs), or vehicle, was
      injected (5, 25, 50, 100, 200, and 300 mg/kg body weight/day) into the mice
      subcutaneously once a day for 3 weeks from the day of implantation of the bone
      morphogenetic protein (BMP)-laden disks. The rhBMP-2-induced ectopic ossicles
      were harvested and examined using radiographic, histological, and biochemical
      methods to determine size, bone quality, and calcium content. When compared with
      controls, ossicles from mice treated with >50 mg/kg per day of PTX were
      significantly larger in size and had a greater calcium content. However, no
      differences were noted in mice treated with lower doses (5 and 25 mg/kg per day)
      of PTX. The temporal sequence of the bone-forming process was unchanged by PTX
      based on histological examination. The histology of the ossicles from high- and
      low-dose PTX-treated mice was essentially identical to that observed in the
      control mice. These experimental results indicate that PTX enhanced the bone
      inducing capacity of BMP-2. The underlying mechanism of action most likely
      involves the inhibition of intracellular phosphodiesterases and a resulting
      elevation of the intracellular content of cyclic nucleotides. Further studies are
      warranted to understand how BMP-induced bone formation is pharmacologically
      modified by PTX.

PMID- 11248660
TI  - A nonhuman primate model of age-related bone loss: a longitudinal study in male
      and premenopausal female rhesus monkeys.
AB  - Aging is associated with gradual bone loss in men and premenopausal women, with
      an accelerated rate of loss after menopause in women. Although many studies have
      investigated bone loss due to surgically induced estrogen depletion, little is
      known regarding normal age-related changes in bone mass in animal models. We used
      dual-energy X-ray absorptiometry (DXA) to measure bone mineral density (BMD),
      bone mineral content (BMC), and projected area (PA) at four skeletal sites over 4
      years in 20 premenopausal female (8-23 years) and 29 male (8-27 years) rhesus
      monkeys (Macaca mulatta). Forearm BMD declined with age in both male and female
      monkeys. Lean mass was positively associated with BMD at all sites in males and
      with the distal radius in females. Serum osteocalcin declined and urinary cross
      links increased with age in males but not females. Serum 25-hydroxyvitamin D
      concentrations decreased with age in females, and a similar trend was observed in
      males. In conclusion, an age-related decline in forearm BMD was observed in male
      and female rhesus monkeys. Total body BMC declined over time in older females,
      with a similar trend in males. Changes in markers of bone turnover with age were
      also observed in male monkeys. The results of this longitudinal study suggest
      that the rhesus monkey is a potential model for age-related changes in the human
      skeleton.

PMID- 11248661
TI  - Messenger-RNA expression of matrix metalloproteinases, tissue inhibitors of
      metalloproteinases, and transcription factors in rheumatic synovial cells under
      mechanical stimuli.
AB  - In an effort to elucidate the role of mechanical stimuli in rheumatoid arthritis,
      we determined mRNA levels of matrix metalloproteinase (MMP)-1, MMP-3, MMP-13,
      tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2, and three
      transcription factors (c-fos, ets-1, and ets-2) under two mechanical shearing
      conditions as well as simulated unloading. Human synovial cell cultures (MH7A and
      RA99-01), derived from rheumatoid arthritis patients, were grown for 1 h under
      mechanical stimuli and the transcript level was assayed by the reverse
      transcription-polymerase-chain reaction procedure. First, gentle shearing,
      estimated at approximately 1 dyn/cm(2), induced a consistent decrease in mRNA
      level of MMP-1, MMP-3, MMP-13, and ets-1 and an increase in the transcript level
      of TIMP-1, TIMP-2, c-fos, and ets-2. Second, intermediate shearing, estimated at
      approximately 6 dyn/cm(2), elevated the mRNA level of all MMPs, TIMPs, and the
      three transcription factors. Third, minimum mRNA level of c-fos, ets-1, and ets-2
      was achieved under control conditions at rest, gentle shearing, and simulated
      unloading, respectively. These in vitro results support a stimulus-dependent
      transcriptional regulation of MMPs, TIMPs, and transcription factors in cell
      cultures, suggesting a potential role of shear stress in tissue degradation and
      prevention in rheumatic joints.

PMID- 11248663
TI  - Vertebral involvement in hyperphosphatemic tumoral calcinosis.
AB  - Hyperphosphatemic tumoral calcinosis (HTC) is an inherited metabolic disorder
      characterized by calcified soft tissue masses and hyperphosphatemia. Besides
      these typical features, a number of less common manifestations have been
      reported, all of them related to pathologic calcification of various tissues. We
      have investigated the case of a woman with hyperphosphatemia, recurrent episodes
      of lumbar pain, and a positive familial history of HTC. A bone scan showed
      markedly increased uptake in the lower lumbar spine. Magnetic resonance imaging
      showed pathological changes in L5 compatible with an inflammatory reaction and
      not suggestive of neoplastic process. There was no evidence of infection, trauma,
      malignancy, or other disease that could cause the lesion. We treated the patient
      with analgesics and NSAIDs and the pain remitted over a period of 1 week. In a
      follow-up magnetic resonance imaging 7 months later, the L5 lesion had
      disappeared completely. A computed tomography scan analysis with a bone window
      showed a sclerotic area at the L5 vertebral body. We believe that this patient
      was affected by the syndrome of HTC and that the inflammatory phenomena found in
      L5 are a manifestation of this disease.

PMID- 11248662
TI  - Effects of clodronate on vertebral fracture risk in osteoporosis: a 1-year
      interim analysis.
AB  - The aim of this study was to determine whether clodronate reduced the incidence
      of vertebral fractures in patients with osteoporosis. We report here the interim
      analysis after 1 year of a 3-year double-blind placebo-controlled study. The
      objectives of the interim analysis were to determine whether there was a trend in
      fracture frequency and to examine the effects of clodronate on bone mineral
      density (BMD). Patients with densitometrically proven osteoporosis (T-score <-2.5
      and <-3 for women and men, respectively) or with at least one prevalent vertebral
      fracture were recruited to a 3-year double-blind, controlled study. Patients were
      randomized to three strata, namely women with postmenopausal osteoporosis
      (stratum I, n = 483), women with secondary osteoporosis (II, n = 110), and men
      with osteoporosis of any causation (III, n = 84). They received either clodronate
      800 mg daily by mouth or an identical placebo, and all patients received a
      calcium supplement of 500 mg daily. BMD was measured at six monthly intervals,
      and lateral spine radiographs for vertebral morphometry were obtained at baseline
      and 1 year. Treatment with clodronate was associated with a significant increase
      in BMD at the spine of 3.2 +/- 0.3% (p < 0.0001 vs. baseline) compared with a
      nonsignificant change of 0.5 +/- 0.3% in the placebo group (p < 0.0001 between
      treatments). At the hip, clodronate was associated with a significant increase in
      total hip BMD of 1.3 +/- 0.3% (p = 0.018 vs. baseline) compared with a small
      decrease of 0.4 +/- 0.3% in the placebo group (p = 0.027 for the difference
      between treatment groups). The mean changes at the spine and hip were similar in
      all three strata. Incident vertebral fractures were observed in 27 patients at 1
      year in the placebo group (9.0%) and in 14 patients receiving clodronate (4.9%)
      (relative risk 0.54; 95% CI 0.29-1.02; p = 0.07). A trend was observed in all
      treatment strata. Treatment was well tolerated, with no significant adverse
      events attributable to clodronate treatment. We conclude that clodronate 800 mg
      daily is effective in preventing bone loss, and at 1 year, there is a trend
      consistent with antifracture efficacy in patients with established osteoporosis
      regardless of causation.

PMID- 11248664
TI  - A new enzyme-linked immunosorbant assay for the measurement of human vitamin D
      receptor.
AB  - The hormonal actions of 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] are
      mediated by its cognate receptor protein, the vitamin D receptor (VDR). Despite
      the growing importance of the VDR system as a modulator of cell growth and
      differentiation, convenient assays for quantitative measurement of VDR are not
      readily available, and [(3)H]1,25(OH)(2)D(3) ligand binding assays remain the
      standard method. In this paper, we present data to validate and characterize the
      usefulness of a new VDR enzyme-linked immunosorbant assay (ELISA) kit developed
      for the measurement of VDR in biological samples. In this assay, samples are
      added to microtitration wells coated with anti-VDR antibody and incubated with a
      second anti-VDR antibody that is biotinylated. The antibody receptor complex is
      then detected with streptavidin-labeled horseradish peroxidase followed by
      incubation with a chromogenic substrate, tetramethylbenzidine. The assay was
      found to be sensitive and accurate for measurements of VDR and compared favorably
      with the conventional radioligand binding assay (RBA). The interassay variation
      ranged from 5% to 25% and the intraassay variation was less than 5%. The ELISA
      presents several advantages over existing methodology, including the use of
      nonradioactive detection systems, lower protein and sample volume requirements,
      as well as convenience and speed. The assay can be completed in as short a time
      as 3 h, avoiding overnight incubations. Data are also presented to demonstrate
      the ability of the ELISA to detect both occupied and unoccupied VDR, making it a
      valuable research tool in settings where 1,25(OH)(2)D(3) is present. However, the
      ELISA, as currently formulated, is only useful for the detection of human VDR.

PMID- 11248665
TI  - Bone loss in relation to menopause: a prospective study during 16 years.
AB  - This prospective study evaluated bone loss in the peri- and postmenopausal period
      in 156 women followed from age 48 to 64 years. All women were premenopausal at
      the start of the study. Areal bone mineral density (g/cm(2)) was measured by
      single-photon absorptiometry (SPA) of the forearm at the 1 cm level (BMD 1 cm)
      and the 6 cm level (BMD 6 cm) every second year. Onset of menopause (MP) was
      determined according to the criteria of the World Health Organization (12 months
      of amenorrhea and elevated follicle-stimulating hormone). At the end of the
      study, 125 of 156 women (80%) remained. Bone mineral density (BMD) at age 48
      years correlated with BMD at age 64 years within the respective region (r = 0.4
      0.5, p < 0.001, respectively). There was no BMD loss in the premenopausal period.
      BMD loss was accelerated at menopause (MP) independent of chronological age. BMD
      loss was greater during the first 5 years following MP than during the following
      6 years (BMD 1 cm 2.4% per year [1.0%-3.9%] vs. 0.4% per year [-0.3%-1.0%], p <
      0.01). The quartile of women with late MP (>53.7 years) had greater bone loss
      during the first 5 years after MP than the quartile of women with early MP (<50.3
      years) (p < 0.001). At age 64 years, BMD was no different when comparing the
      quartile of women with late MP vs. the quartile of women with early MP.
      Furthermore, there was no correlation between age at menopause and BMD at the age
      of 64. In summary, among women still menstruating at age 48 years, there was no
      measurable BMD loss in the premenopausal period. Independent of chronological
      age, BMD loss accelerated during MP. Rates of loss were highest in the early
      postmenopausal period. Independent of age at MP, premenopausal women with low age
      specific BMD at age 48 years had an increased risk of sustaining low BMD at age
      64 years also.

PMID- 11248666
TI  - Effect of coffee consumption on bone metabolism.
AB  - The effects of coffee on bone metabolism are still controversial, although
      several studies have suggested that caffeine and/or heavy coffee consumption is
      associated with a significant increase in risk of fracture, osteoporosis, and
      periodontal disease. Therefore, we sought to clarify the relationship between
      coffee consumption and bone metabolism using male Wistar rats. Forty-eight male
      Wistar rats were assigned to three treatment groups including a control-diet
      group (control, n = 16, coffee-free diet), a 0.62% coffee-diet group (low
      caffeine, n = 16, diet supplemented with 6.2 g/kg of the control diet), and a
      1.36% coffee-diet group (high caffeine, n = 16, diet supplemented with 13.6 g/kg
      of the control diet), and animals were maintained on an experimental diet for 140
      days. Although caffeine in serum was not detected in rats fed the control diet,
      low-intake coffee for 140 days led to an increase in caffeine concentration to
      0.53 +/- 0.11 microg/mL and high-intake coffee led to an increase of 1.77 +/-
      0.22 microg/mL. No significant differences in body weight change, serum and
      urinary biochemical markers of bone metabolism, and bone histomorphometry were
      found between the coffee-diet groups and the control-diet group, except that
      urinary phosphorus excretion after 140 days of both coffee diets was
      significantly increased compared with controls (p < 0.05). In addition, the
      coffee diets were not associated with differences in tumor necrosis factor-alpha
      and interleukin-6, which have been implicated in the pathogenesis of bone loss
      together with interleukin-1beta. In conclusion, the present study strongly
      indicates that coffee does not stimulate bone loss in rats.

PMID- 11248668
TI  - The protein kinase Cdk5. Structural aspects, roles in neurogenesis and
      involvement in Alzheimer's pathology.
AB  - A set of different protein kinases have been involved in tau phosphorylations,
      including glycogen synthase kinase 3beta (GSK3 beta), MARK kinase, MAP kinase,
      the cyclin-dependent kinase 5 (Cdk5) system and others. The latter system include
      the catalytic component Cdk5 and the regulatory proteins p35, p25 and p39. Cdk5
      and its neuron-specific activator p35 are essential molecules for neuronal
      migration and for the laminar configuration of the cerebral cortex. Recent
      evidence that the Cdk5/p35 complex concentrates at the leading edge of axonal
      growth cones, together with the involvement of this system in the phosphorylation
      of neuronal microtubule-asociated proteins (MAPs), provide further support to the
      role of this protein kinase in regulating axonal extension in developing brain
      neurons. Although the aminoacid sequence of p35 has little similarity with those
      of normal cyclins, studies have shown that its activation domain may adopt a
      conformation of the cyclin-folded structure. The computed structure for Cdk5 is
      compatible with experimental data obtained from studies on the Cdk5/p35 complex,
      and has allowed predictions on the protein interacting domains. This enzyme
      exhibits a wide cell distribution, even though a regulated Cdk5 activity has been
      shown only in neuronal cells. Cdk5 has been characterized as a proline-directed
      Ser/Thr protein kinase, that contributes to phosphorylation of human tau on
      Ser202, Thr205, Ser235 and Ser404. Cdk5 is active in postmitiotic neurons, and it
      has been implicated in cytoskeleton assembly and its organization during axonal
      growth. In addition to tau and other MAPs, Cdk5 phosphorylates the high molecular
      weight neurofilament proteins at their C-terminal domain. Moreover, nestin, a
      protein that regulates cytoskeleton organization of neuronal and muscular cells
      during development of early embryos, and several other regulatory proteins appear
      to be substrates of Cdk5 and are phosphorylated by this kinase. Studies also
      suggest, that in addition to Cdk5 involvement in neuronal differentiation, its
      activity is induced during myogenesis, however, the mechanisms of how this
      activity is regulated during muscular differentiation has not yet been
      elucidated. Recent studies have shown that the beta-amyloid peptide (A beta)
      induces a deregulation of Cdk5 in cultured brain cells, and raises the question
      on the possible roles of this tau-phosphorylating protein kinase in the sequence
      of molecular events leading to neuronal death triggered by A beta. In this
      context, there are evidence that Cdk5 is involved in tau hyperphosphorylation
      promoted by A beta in its fibrillary form. Cdk5 inhibitors protect hippocampal
      neurons against both tau anomalous phosphorylations and neuronal death. The links
      between the studies on the Cdk5/p35 system in normal neurogenesis and its claimed
      participation in neurodegeneration, provide the framework to understand the
      regulatory relevance of this kinase system, and changes in its regulation that
      may be implicated in disturbances such as those occurring in Alzheimer disease.

PMID- 11248669
TI  - The role of the Cdk5--p35 kinase in neuronal development.
AB  - Cyclin-dependent kinase 5 (Cdk5) plays a key role in proper development of the
      nervous system. To be activated, Cdk5 associates with regulatory subunits not
      related to cyclins, such as p35 (the regulatory subunit of Cdk5). In this
      article, we review some of the experimental evidence supporting a central role
      for the Cdk5/p35 kinase in neuronal migration and process formation.

PMID- 11248670
TI  - Cyclin-dependent protein kinase 5 (Cdk5) and the regulation of neurofilament
      metabolism.
AB  - Cyclin-dependent kinase 5 (Cdk5), a complex of Cdk5 and its activator p35
      (Cdk5/p35), phosphorylates diverse substrates which have multifunctional roles in
      the nervous system. During development, it participates in neuronal
      differentiation, migration, axon outgrowth and synaptogenesis. Cdk5, acting
      together with other kinases, phosphorylates numerous KSPXK consensus motifs in
      diverse cytoskeletal protein target molecules, including neurofilaments, and
      microtubule associated proteins, tau and MAPs. Phosphorylation regulates the
      dynamic interactions of cytoskeletal proteins with one another during all aspects
      of neurogenesis and axon radial growth. In this review we shall focus on Cdk5 and
      its regulation as it modulates neurofilament metabolism in axon outgrowth,
      cytoskeletal stabilization and radial growth. We suggest that Cdk5/p35 forms
      compartmentalized macromolecular complexes of cytoskeletal substrates, other
      neuronal kinases, phosphatases and activators ('phosphorylation machines') which
      facilitate the dynamic molecular interactions that underlie these processes.

PMID- 11248671
TI  - Kinetic analysis of a simplified scheme of autocatalytic zymogen activation.
AB  - Proteolytic enzymes are usually biosynthesized as somewhat larger inactive
      precursors known as zymogens. These zymogens must undergo an activation process,
      usually a limited proteolysis, to attain their catalytic activity. When the
      activating enzyme and the activated enzyme coincide, the process is an
      autocatalytic zymogen activation. In the present study, a kinetic analysis of the
      entire progress curve for the autocatalytic zymogen activation reactions is
      presented. On the basis of the kinetic equations, a novel procedure is developed
      to evaluate the kinetic parameters of the reactions. This procedure is
      particularly useful for the fast zymogen autoactivation reactions. As two
      examples, the novel procedure is used to analyse the autocatalytic activation of
      bovine trypsinogen and human blood coagulation factor XII (Hageman factor).

PMID- 11248672
TI  - Thermodynamic analysis of binding of p-substituted benzamidines to trypsin.
AB  - Understanding the structural basis of inhibitor-enzyme interactions, important
      for the design of new drugs, requires a complete thermodynamic characterization
      of the binding process as well as a description of the structure of the complex.
      In this paper, the binding of p-substituted benzamidinium derivatives to the
      structurally well-characterized serine proteinase bovine pancreatic trypsin has
      been studied using isothermal titration calorimetry. These experiments have
      permitted a complete characterization of the temperature dependence of the
      inhibitor-binding thermodynamics. At 25 degrees C, both the enthalpy and entropy
      of binding are favourable for all studied derivatives, but this is only true for
      a relatively narrow temperature range. As binding is characterized by a negative
      change in heat capacity, the process is characterized by enthalpy--entropy
      compensation, resulting in a change of the net thermodynamic driving force for
      association from entropic to enthalpic with increasing temperature. These
      phenomena are not unusual when hydrophobic forces play an important role. The
      trend in the relative binding potencies can, to a significant extent, be
      attributed to the electron-donating/withdrawing character of the substituent at
      the para position, as shown by the Hammett sigma(p)(+) plot for the different
      inhibitors; the more polar the p-substituted benzamidine, the less potent it will
      be as a trypsin inhibitor. This behaviour might result from a bulk solvation
      effect, meaning that the more polar, lower potency inhibitors will be more
      stabilized in water than the less polar, higher potency inhibitors.

PMID- 11248673
TI  - P-glycoprotein preferentially effluxes anthracyclines containing free basic
      versus charged amine.
AB  - The multidrug resistant (MDR) tumor phenotype, characterized by a decreased
      cellular drug accumulation is achieved by ATP-dependent extrusions of drugs from
      cells by P-glycoprotein (P-gp) and/or by multidrug resistance protein (MRP1).
      Despite the huge amount of research that has been performed on the mechanisms of
      P-gp-mediated efflux of drug, it is not yet known what the molecular parameters
      are required for a molecule to be recognized and pumped out by P-gp.
      Anthracyclines are weak bases and, depending on the pH, can exist either in the
      neutral or in the positively charged form. The aim of the work reported here was
      to determine which molecular form is actively pumped out by P-gp (the neutral
      form, the protonated form, or both), and if both, the relative efficiencies of
      pumping. We used spectrofluorometric methods to determine the efflux of
      anthracyclines in K562/Adr cells, at different intracellular and extracellular pH
      levels. Using 3'-deamino, 3'-hydroxyl doxorubicin (OH-DOX), which is permanently
      neutral, we first verified that our methodologies were accurate and that the P-gp
      mediated efflux of OH-DOX would not depend on the pH being in the range 6.6--8.4.
      The P-gp-mediated efflux of daunorubicin (DNR) and 3'-hydroxy-4-amino (WP608) was
      determined at different pH values. These two drugs were chosen because: (a) the
      lipophilicity of the neutral forms of these two molecules is so similar that any
      difference in the P-gp-mediated efflux cannot be assigned to lipohilicity
      variation, and (b) their pKa values are different (8.4 and 7.7 for DNR and WP608,
      respectively), which makes it easy to obtain a large variation in the proportions
      of the neutral and positively charged forms. Our data show that both forms are
      recognized by P-gp but the neutral form is pumped about three times more
      efficiently than the charged form. This is corroborated by results showing the
      active efflux (checked at pH(i) 7.3 only) of five other anthracycline containing
      a basic center. We interpret these data to mean that: (a) the positive charge of
      anthracycline is not a necessary requirement for P-gp recognition, but that (b)
      the presence of a protonable basic nitrogen facilitates the processing of these
      compounds by MDR efflux system.

PMID- 11248674
TI  - Diguanosine nucleotide metabolism and the survival of artemia embryos during
      years of continuous anoxia.
AB  - Encysted embryos of the primitive crustacean, Artemia franciscana, are remarkably
      resistant to a variety of harsh environmental conditions, including continuous
      anoxia for periods of years at physiological temperatures and water contents.
      Previous study produced no evidence of an ongoing anoxic metabolism, suggesting
      that these embryos remained viable in spite of the lack of detectable free energy
      flow and biosynthesis. That seeming violation of a major axiom of cell biology
      and biochemistry prompted us to re-examine the nucleotide pool of encysted
      embryos during prolonged anoxia. We found that the nucleotide Gp(4)G, present
      initially in very large amounts, decreased slowly as anoxia continued over the
      5.6-year period examined. Studies on other nucleotides and associated enzymes,
      including results from previous papers, provide a plausible metabolic pathway
      leading to the provision of ATP and GTP to meet the needs of endergonic processes
      in anoxic embryos. Exactly what those processes are is not obvious. One
      possibility involves the extensive anoxia-induced nuclear translocation of the
      stress protein, molecular chaperone p26, whose large molecular mass
      (approximately 500 kDa) most likely requires a supply of free energy to cross the
      nuclear envelope. Support for this possibility comes from our finding here that
      p26 is also a GTPase.

PMID- 11248675
TI  - The rainbow trout (Oncorhynchus mykiss) Mx1 promoter. Structural and functional
      characterization.
AB  - Mx1 gene expression was studied in the rainbow trout (Oncorhynchus mykiss) gonad
      (RTG) (fibroblast) cell line. RT-PCR analyses showed that both poly I:C and
      interferon containing supernatants induced expression of Mx1 in RTG cells.
      Kinetic analyses suggest that poly I:C acts indirectly through the production of
      interferons (IFN), as shown in other studies. By gene walking with trout genomic
      DNA the regulatory sequence of the Mx1 gene was cloned and sequenced. Sequence
      analysis showed that the 5' flanking region has a structure, which is typical for
      an interferon-induced gene promoter. Relative to the transcription start, it has
      a TATA box at -29 to -25, a 13 nucleotide interferon response element (ISRE)
      between -101 to -89, and a Sp1 binding site at -382 to -374. This region, with a
      single ISRE, is enough to induce strong expression of a luciferase reporter gene
      after stimulation of RTG cells with poly I:C. A time-course of induction of this
      reporter construct showed maximal expression (22-fold increase) after incubation
      with 100 microg mL(-1) poly I:C for 48 h. An optimized method of transient
      transfection of RTG cells is also described.

PMID- 11248676
TI  - SUT1 is a putative Zn[II]2Cys6-transcription factor whose upregulation enhances
      both sterol uptake and synthesis in aerobically growing Saccharomyces cerevisiae
      cells.
AB  - Budding yeast Saccharomyces cerevisiae is a facultative anaerobe whose growth
      upon oxygen starvation depends on its capacity to import exogenously supplied
      sterols, whereas the cells are not permeable to these molecules when grown
      aerobically. Few genes have been identified as being involved in sterol uptake. A
      higher SUT1 gene dosage leads to a modest, but significant, increase in sterol
      uptake under aerobic conditions. Based on sequence and physiological data, SUT1
      is a hypoxic gene negatively regulated when the cells are grown in the presence
      of oxygen. We replaced the SUT1 promoter with the constitutive PMA1 gene promoter
      in order to enhance its transcription. We observed that sterol uptake was then
      comparable with that obtained with a sterol importing hem1 mutant, although the
      heme status of the strain was not modified in a process which still occurs when
      the cells are not growing. Unexpectedly, SUT1 constitutive expression led to a
      parallel significant increase in endogenous sterol biosynthesis. Moreover, here
      we present new data showing that the structurally related YPR009 gene (SUT2) is a
      functional homologue of SUT1, and that both gene products may represent two novel
      yeast regulatory proteins involved in sterol uptake.

PMID- 11248677
TI  - Biosynthesis of cannabinoids. Incorporation experiments with (13)C-labeled
      glucoses.
AB  - The biosynthesis of cannabinoids was studied in cut sprouts of Cannabis sativa by
      incorporation experiments using mixtures of unlabeled glucose and [1
      (13)C]glucose or [U-(13)C(6)]glucose. (13)C-labeling patterns of cannabichromenic
      acid and tetrahydrocannabinolic acid were analyzed by quantitative NMR
      spectroscopy. (13)C enrichments and coupling patterns show that the C(10)
      terpenoid moiety is biosynthesized entirely or predominantly (> 98%) via the
      recently discovered deoxyxylulose phosphate pathway. The phenolic moiety is
      generated by a polyketide-type reaction sequence. The data support geranyl
      diphosphate and the polyketide, olivetolic acid, as specific intermediates in the
      biosynthesis of cannabinoids.

PMID- 11248678
TI  - A 'select and swap' strategy for the isolation of clones with tightly regulated
      transgenes.
AB  - Increasing numbers of biological problems are being addressed by genetic
      approaches that rely on inducible expression of transgenes. It is desirable that
      expression of such a transgene is tightly regulated, from close to zero
      expression in the 'off' state, to appreciable (at least physiological) expression
      in the 'on' state. Although there are many examples where tight regulation has
      been achieved, certain factors, including chromosomal position effects due to
      random integration of the transgene, often cause suboptimal inducibility and make
      the isolation of tightly regulated clones difficult and/or laborious. Here we
      describe a 'select and swap' strategy for the isolation, from a population of
      stable transfectants, of clones with tightly regulated transgenes. In this
      approach, a positively and negatively selectable, inducible marker gene is used
      to select for clones with optimal transgene regulation. After isolation of such
      clones, the marker gene is swapped with a linked gene of interest by the use of
      site-specific recombination. To test this strategy we introduced into human cells
      a plasmid with a tetracycline-inducible bacterial gpt gene linked to a
      promoterless luciferase gene, isolated clones with tight gpt expression and used
      the Cre/loxP site-specific recombination system to swap the gpt gene with the
      luciferase gene. We discuss ways for refining and developing the system and
      widening its applicability.

PMID- 11248679
TI  - Characterization of carbonic anhydrase from Neisseria gonorrhoeae.
AB  - We have investigated the steady state and equilibrium kinetic properties of
      carbonic anhydrase from Neisseria gonorrhoeae (NGCA). Qualitatively, the enzyme
      shows the same kinetic behaviour as the well studied human carbonic anhydrase II
      (HCA II). This is reflected in the similar pH dependencies of the kinetic
      parameters for CO(2) hydration and the similar behaviour of the kinetics of (18)O
      exchange between CO(2) and water at chemical equilibrium. The pH profile of the
      turnover number, k(cat), can be described as a titration curve with an
      exceptionally high maximal value of 1.7 x 10(6) s(-1) at alkaline pH and a pK(a)
      of 7.2. At pH 9, k(cat) is buffer dependent in a saturable manner, suggesting a
      ping-pong mechanism with buffer as the second substrate. The ratio k(cat)/K(m) is
      dependent on two ionizations with pK(a) values of 6.4 and 8.2. However, an (18)O
      exchange assay identified only one ionizable group in the pH profile of
      k(cat)/K(m) with an apparent pK(a) of 6.5. The results of a kinetic analysis of a
      His66-->Ala variant of the bacterial enzyme suggest that His66 in NGCA has the
      same function as a proton shuttle as His64 in HCA II. The kinetic defect in the
      mutant can partially be overcome by certain buffers, such as imidazole and 1,2
      dimethylimidazole. The bacterial enzyme shows similar K(i) values for the
      inhibitors NCO(-), SCN(-) and N(3)(-) as HCA II, while CN(-) and the sulfonamide
      ethoxzolamide are considerably weaker inhibitors of the bacterial enzyme than of
      HCA II. The absorption spectra of the adducts of Co(II)-substituted NGCA with
      acetazolamide, NCO(-), SCN(-), CN(-) and N(3)(-) resemble the corresponding
      spectra obtained with human Co(II)-isozymes I and II. Measurements of guanidine
      hydrochloride (GdnHCl)-induced denaturation reveal a sensitivity of the CO(2)
      hydration activity to the reducing agent tris(2-carboxyethyl)phosphine (TCEP).
      However, the A(292)/A(260) ratio was not affected by the presence of TCEP, and a
      structural transition at 2.8--2.9 M GdnHCl was observed.

PMID- 11248680
TI  - Solution structure of cytochrome b(5) mutant (E44/48/56A/D60A) and its
      interaction with cytochrome c.
AB  - Using 1617 meaningful NOEs with 188 pseudocontact shifts, a family of 35
      conformers of oxidized bovine microsomal cytochrome b5 mutant (E44/48/56A/D60A)
      has been obtained and is characterized by good resolution (rmsd to the mean
      structure are 0.047 +/- 0.007 nm and 0.095 +/- 0.008 nm for backbone and heavy
      atoms, respectively). The solution structure of the mutant, when compared with
      the X-ray structure of wild-type cytochrome b(5), has no significant changes in
      the whole folding and secondary structure. The binding between cytochrome b(5)
      and cytochrome c shows that the association constant of the mutant-cytochrome c
      complex is much lower than the one for wild-type complex (2.2 x 10(4) M(-1) vs.
      5.1 x 10(3) M(-1)). The result suggests the four acidic residues have substantial
      effects on the formation of the complex between cytochrome b(5) and cytochrome c,
      and therefore it is concluded reasonably that the electrostatic interaction plays
      an important role in maintaining the stability and specificity of the complex
      formed. The competition between the ferricytochrome b(5) mutant and
      [Cr(oxalate)(3)](3-) for ferricytochrome c shows that site III of cytochrome c,
      which is a strong binding site to wild-type cytochrome b(5), still binds to the
      mutant with relatively weaker strength. Our results indicate that certain bonding
      geometries do occur in the interaction between the present mutant and cytochrome
      c and these geometries, which should be quite different from the ones of the
      Salemme and Northrup models.

PMID- 11248681
TI  - Palmitoylation of the luteinizing hormone/human chorionic gonadotropin receptor
      regulates receptor interaction with the arrestin-mediated internalization
      pathway.
AB  - The luteinizing hormone/human chorionic gonadotropin receptor (LH/hCGR) undergoes
      palmitoylation at cysteine residues 621 and 622 located in the carboxyl terminal
      tail of the receptor. This study examined the biological function of
      palmitoylation with respect to its effect on receptor internalization.
      Coexpression of wild-type (WT) or C621/622G mutant receptors with arrestin-2
      increased receptor internalization in 293T cells. Furthermore, measurements of
      rate enhancement upon overexpression of arrestin indicate that the palmitoylation
      deficient mutant receptor is more prone to utilizing the arrestin mediated
      internalization pathway than the WT receptor. Coexpression of G-protein-coupled
      receptor kinase 4 (GRK4) with wild type receptor resulted in an increase in
      internalization, while coexpression with the mutant receptor did not result in
      further enhancement of internalization. Additionally, 293T cells expressing
      mutant receptor were responsive to hCG with respect to production of inositol
      phosphates. Taken together, these results suggest that the palmitoylation state
      of the receptor governs internalization by regulating the accessibility of the
      receptor to the arrestin-mediated internalization pathway.

PMID- 11248682
TI  - Contributions of the substrate-binding arginine residues to maleate-induced
      closure of the active site of Escherichia coli aspartate aminotransferase.
AB  - Crystallography shows that aspartate aminotransferase binds dicarboxylate
      substrate analogues by bonds to Arg292 and Arg386, respectively [Jager, J, Moser,
      M. Sauder, U. & Jansonius, J. N. (1994) J. Mol. Biol., 239, 285-305]. The
      contribution of each interaction to the conformational change that the enzyme
      undergoes when it binds ligands via these residues, is assessed by probing mutant
      forms of the enzyme lacking either or both arginines. The probes used are
      NaH(3)BCN which reduces the cofactor imine, the reactive substrate analogue,
      cysteine sulfinate and proteolysis by trypsin. The unreactive substrate analogue,
      maleate, is used to induce closure. Each single mutant reacted only 2.5-fold more
      slowly with NaH(3)BCN than the wild-type indicating that charge repulsion by the
      arginines contributes little to maintaining the open conformation. Maleate
      lowered the rate of reduction of the wild-type enzyme more than 300-fold but had
      little effect on the reaction of the mutant enzymes indicating that the ability
      of this dicarboxylate analogue to bridge the arginines precisely makes the major
      contribution to closure. The R292L mutant reacted 20 times more rapidly with
      cysteine sulfinate than R386L but 5 x 10(4) times more slowly than the wild-type
      enzyme, consistent with the proposal that enzyme's catalytic abilities are not
      developed unless closure is induced by bridging of the arginines. Proteolysis of
      the mutants with trypsin showed that, in the wild-type enzyme, the bonds most
      susceptible to trypsin are those contributed by Arg292 and Arg386. Proteolysis of
      the next most susceptible bond, at Arg25 in the double mutant, was protected by
      maleate demonstrating the presence of an additional site on the enzyme for
      binding dicarboxylates.

PMID- 11248683
TI  - Cellular expression and functional characterization of four hyperpolarization
      activated pacemaker channels in cardiac and neuronal tissues.
AB  - Hyperpolarization-activated cation currents (I(h)) have been identified in
      cardiac pacemaker cells and a variety of central and peripheral neurons. Four
      members of a gene family encoding hyperpolarization-activated, cyclic nucleotide
      gated cation channels (HCN1--4) have been cloned recently. Native I(h) currents
      recorded from different cell types exhibit distinct activation kinetics. To
      determine if this diversity of I(h) currents may be caused by differential
      expression of HCN channel isoforms, we investigated the cellular distribution of
      the transcripts of HCN1--4 in the murine sinoatrial node, retina and dorsal root
      ganglion (DRG) by in situ hybridization. In the sinoatrial node, the most
      prominently expressed HCN channel is HCN4, whereas HCN2 and HCN1 are detected
      there at moderate and low levels, respectively. Retinal photoreceptors express
      high levels of HCN1, whereas HCN2, 3 and 4 were not found in these cells. In DRG
      neurons, the dominant HCN transcript is HCN1, followed by HCN2. We next
      determined the functional properties of recombinant HCN1--4 channels expressed in
      HEK293 cells. All four channel types gave rise to I(h) currents but displayed
      marked differences in their activation kinetics. Our results suggest that the
      heterogeneity of native I(h) currents is generated, at least in part, by the
      tissue-specific expression of HCN channel genes.

PMID- 11248684
TI  - A new iron oxidase from a moderately thermophilic iron oxidizing bacterium strain
      TI-1.
AB  - Iron oxidase was purified from plasma membranes of a moderately thermophilic iron
      oxidizing bacterium strain TI-1 in an electrophoretically homogeneous state.
      Spectrum analyses of purified enzyme showed the existence of cytochrome a, but
      not cytochrome b and c types. Iron oxidase was composed of five subunits with
      apparent molecular masses of 46 kDa (alpha), 28 kDa (beta), 24 kDa (gamma), 20
      kDa (delta), and 17 kDa (epsilon). As the molecular mass of a native enzyme was
      estimated to be 263 kDa in the presence of 0.1% n-dodecyl-beta-D-maltopyranoside
      (DM), a native iron oxidase purified from strain TI-1 seems to be a homodimeric
      enzyme (alpha beta gamma delta epsilon)(2). Optimum pH and temperature for iron
      oxidation were pH 3.0 and 45 degrees C, respectively. The K(m) of iron oxidase
      for Fe(2+) was 1.06 mM and V(max) for O(2) uptake was 13.8 micromol x mg(-1) x
      min(-1). The activity was strongly inhibited by cyanide and azide. Purified
      enzyme from strain TI-1 is a new iron oxidase in which electrons of Fe(2+) were
      transferred to haem a and then to the molecular oxygen.

PMID- 11248685
TI  - Kinetics of membrane lysis by custom lytic peptides and peptide orientations in
      membrane.
AB  - To aid the development of custom peptide antibiotics, a kinetic study of membrane
      lysis by cecropin B (CB) and its analogs, cecropin B1 (CB1) and cecropin B3 (CB3)
      was carried out to determine the mechanism by which these peptides disrupt the
      bilayer structure of liposomes of defined composition. Disruption of the
      phospholipid bilayer was determined by a fluorescence assay involving the use of
      dithionite to quench the fluorescence of lipids labeled with N-7-nitro-2,1,3
      benzoxadiazol-4-yl. Lytic peptides caused the disruption of liposomes to occur in
      two kinetic steps. For liposomes composed of mixtures of phosphatidylcholine and
      phosphatidic acid, the time constants for each kinetic step were shorter for CB
      and CB1 than for CB3. Oriented circular dichroism experiments showed that the
      peptides could exist in at least two different membrane-associated states that
      differed primarily in the orientation of the helical segments with respect to the
      bilayer surface. The results are discussed in terms of kinetic mechanisms of
      membrane lysis. The mode of actions of these peptides used for the interpretation
      of their kinetic mechanisms were supported by surface plasmon resonance
      experiments including or excluding the pore-forming activities.

PMID- 11248686
TI  - ATP-citrate lyase from the green sulfur bacterium Chlorobium limicola is a
      heteromeric enzyme composed of two distinct gene products.
AB  - The reductive tricarboxylic acid cycle functions as a carbon dioxide fixation
      pathway in the green sulfur bacterium, Chlorobium limicola. ATP-citrate lyase,
      one of the key enzymes of this cycle, was partially purified from C. limicola
      strain M1 and the N-terminal sequence of a 65-kDa protein was found to show
      similarity toward eukaryotic ATP-citrate lyase. A DNA fragment was amplified with
      primers designed from this sequence and an internal sequence highly conserved
      among eukaryotic enzymes. Using this fragment as a probe, we isolated a DNA
      fragment containing two adjacent open reading frames, aclB (1197 bp) and aclA
      (1827 bp), whose products showed significant similarity to the N- and C-terminal
      regions of the human enzyme, respectively. Heterologous expression of these genes
      in Escherichia coli showed that both gene products were essential for ATP-citrate
      lyase activity. The recombinant enzyme was purified from the cell-free extract of
      E. coli harboring aclBA for further characterization. The molecular mass of the
      recombinant enzyme was determined to be approximately 532--557 kDa by gel
      filtration. The enzyme catalyzed the cleavage of citrate in an ATP(-), CoA- and
      Mg(2+)-dependent manner, where ATP and Mg(2+) could be replaced by dATP and
      Mn(2+), respectively. ADP and oxaloacetate inhibited the reaction. These
      properties suggested that ATP-citrate lyase from C. limicola controlled the cycle
      flux depending on intracellular energy conditions. This paper provides the first
      direct evidence that a bacterial ATP-citrate lyase is a heteromeric enzyme,
      distinct from mammalian enzymes.

PMID- 11248687
TI  - L-amino-acid oxidase from the Malayan pit viper Calloselasma rhodostoma.
      Comparative sequence analysis and characterization of active and inactive forms
      of the enzyme.
AB  - Here we report the cDNA-deduced amino-acid sequence of L-amino-acid oxidase
      (LAAO) from the Malayan pit viper Calloselasma rhodostoma, which shows 83%
      identity to LAAOs from the Eastern and Western diamondback rattlesnake (Crotalus
      adamanteus and Crotalus atrox, respectively). Phylogenetic comparison of the FAD
      dependent ophidian LAAOs to FAD-dependent oxidases such as monoamine oxidases, D
      amino-acid oxidases and tryptophan 2-monooxygenases reveals only distant
      relationships. Nevertheless, all LAAOs share a highly conserved dinucleotide
      binding fold with monoamine oxidases, tryptophan 2-monooxygenases and various
      other proteins that also may have a requirement for FAD. In order to characterize
      Ca. rhodostoma LAAO biochemically, the enzyme was purified from snake venom to
      apparent homogeneity. It was found that the enzyme undergoes inactivation by
      either freezing or increasing the pH to above neutrality. Both inactivation
      processes are fully reversible and are associated with changes in the UV/visible
      range of the flavin absorbance spectrum. In addition, the spectral
      characteristics of the freeze-and pH-induced inactivated enzyme are the same,
      indicating that the flavin environments are similar in the two inactive
      conformational forms. Monovalent anions, such as Cl(-), prevent pH-induced
      inactivation. LAAO exhibits typical flavoprotein oxidase properties, such as
      thermodynamic stabilization of the red flavin semiquinone radical and formation
      of a sulfite adduct. The latter complex as well as the complex with the
      competitive substrate inhibitor, anthranilate, were only formed with the active
      form of the enzyme indicating diminished accessibility of the flavin binding site
      in the inactive form(s) of the enzyme.

PMID- 11248688
TI  - Drug transport by reconstituted P-glycoprotein in proteoliposomes. Effect of
      substrates and modulators, and dependence on bilayer phase state.
AB  - The P-glycoprotein multidrug transporter (Pgp) is an active efflux pump for
      chemotherapeutic drugs, natural products and hydrophobic peptides. Pgp is
      envisaged as a 'hydrophobic vacuum cleaner', and drugs are believed to gain
      access to the substrate binding sites from within the membrane, rather than from
      the aqueous phase. The intimate association of both Pgp and its substrates with
      the membrane suggests that its function may be regulated by the biophysical
      properties of the lipid bilayer. Using the high affinity fluorescent substrate
      tetramethylrosamine (TMR), we have monitored, in real time, transport in
      proteoliposomes containing reconstituted Pgp. The TMR concentration gradient
      generated by Pgp was collapsed by the addition of either the ATPase inhibitor,
      vanadate, or Pgp modulators. TMR transport by Pgp obeyed Michaelis--Menten
      kinetics with respect to both of its substrates. The Km for ATP was 0.48 mM,
      close to the K(m) for ATP hydrolysis, and the K(m) for TMR was 0.3 microM. TMR
      transport was inhibited in a concentration-dependent fashion by verapamil and
      cyclosporin A, and activated (probably by a positive allosteric effect) by the
      transport substrate colchicine. TMR transport by Pgp reconstituted into
      proteoliposomes composed of two synthetic phosphatidylcholines showed a highly
      unusual biphasic temperature dependence. The rate of TMR transport was relatively
      high in the rigid gel phase, reached a maximum at the melting temperature of the
      bilayer, and then decreased in the fluid liquid crystalline phase. This pattern
      of temperature dependence suggests that the rate of drug transport by Pgp may be
      dominated by partitioning of drug into the bilayer.

PMID- 11248689
TI  - Active oligomeric states of pyruvate decarboxylase and their functional
      characterization.
AB  - Homomeric pyruvate decarboxylase (E.C 4.1.1.1) from yeast consists of dimers and
      tetramers under physiological conditions, a K(d) value of 8.1 microM was
      determined by analytical ultracentrifugation. Dimers and monomers of the enzyme
      could be populated by equilibrium denaturation using urea as denaturant at
      defined concentrations and monitored by a combination of optical (fluorescence
      and circular dichroism) and hydrodynamic methods (analytical
      ultracentrifugation). Dimers occur after treatment with 0.5 M urea, monomers with
      2.0 M urea independent of the protein concentration. The structured monomers are
      catalytically inactive. At even higher denaturant concentrations (6 M urea) the
      monomers unfold. The contact sites of two monomers in forming a dimer as the
      smallest enzymatically active unit are mainly determined by aromatic amino acids.
      Their interactions have been quantified both by structure-theoretical
      calculations on the basis of the X-ray crystallography structure, and
      experimentally by binding of the fluorescent dye bis-ANS. The contact sites of
      two dimers in tetramer formation, however, are mainly determined by electrostatic
      interactions. Homomeric pyruvate decarboxylase (PDC) is activated by its
      substrate pyruvate. There was no difference in the steady-state activity
      (specific activity) between dimers and tetramers. The activation kinetics of the
      two oligomeric states, however, revealed differences in the dissociation constant
      of the regulatory substrate (K(a)) by one order of magnitude. The tetramer
      formation is related to structural consequences of the interaction transfer in
      the activation process causing an improved substrate utilization.

PMID- 11248690
TI  - Expression of coproporphyrinogen oxidase and synthesis of hemoglobin in human
      erythroleukemia K562 cells.
AB  - Coproporphyrinogen oxidase (CPOX), the sixth enzyme in the heme-biosynthetic
      pathway, catalyzes oxidative decarboxylation of coproporphyrinogen to
      protoporphyrinogen and is located in the intermembrane space of mitochondria. To
      clarify the importance of CPOX in the regulation of heme biosynthesis in
      erythroid cells, we established human erythroleukemia K562 cells stably
      expressing mouse CPOX. The CPOX cDNA-transfected cells had sevenfold higher CPOX
      activity than cells transfected with vector only. Expression of ferrochelatase
      and heme content in the transfected cells increased slightly compared with the
      control. When K562 cells overexpressing CPOX were treated with delta
      aminolevulinic acid (ALA), most became benzidine-positive without induction of
      the expression of CPOX or ferrochelatase, and the heme content was about twofold
      higher than that in ALA-treated control cells. Increases in cellular heme
      concomitant with a marked induction of the expression of heme-biosynthetic
      enzymes, including CPOX, ferrochelatase and erythroid-specific delta
      aminolevulinic acid synthase, as well as of alpha-globin synthesis, were observed
      when cells were treated with transforming growth factor (TGF)beta 1. These
      increases in the transfected cells were twice those in control cells, indicating
      that overexpression of CPOX enhanced induction of the differentiation of K562
      cells mediated by TGF beta 1 or ALA. Conversely, the transfection of antisense
      oligonucleotide to human CPOX mRNA into untreated and TGF beta 1-treated K562
      cells led to a decrease in heme production compared with sense oligonucleotide
      transfected cells. These results suggest that CPOX plays an important role in the
      regulation of heme biosynthesis during erythroid differentiation.

PMID- 11248691
TI  - Cyclic dipeptide oxidase from Streptomyces noursei. Isolation, purification and
      partial characterization of a novel, amino acyl alpha,beta-dehydrogenase.
AB  - Cyclic dipeptide oxidase is a novel enzyme that specifically catalyzes the
      formation of alpha,beta-dehydro-Phe (Delta Phe) and alpha,beta-dehydro-Leu (Delta
      Leu) residues during the biosynthesis of albonoursin, cyclo(Delta Phe-Delta Leu),
      an antibiotic produced by Streptomyces noursei. It was purified 600-fold with a
      30% overall recovery, and consists of the association of a single type of subunit
      with a relative molecular mass of 21,066 resulting in a large homopolymer of
      relative molecular mass over 2,000,000. The enzyme exhibits a typical
      flavoprotein spectrum with maxima at 343.5 and 447.5 nm, the flavin prosthetic
      group being covalently bound to the protein. The catalytic reaction of the
      natural substrate cyclo(L-Phe-L-Leu) occurs in a two-step sequential reaction
      leading first to cyclo(alpha,beta-dehydro-Phe-L-Leu) and finally to albonoursin.
      Kinetic parameters for the first step were determined (K(m) = 53 microM; k = 0.69
      s(-1)). The enzyme was shown to catalyze the conversion of a variety of
      cyclo(dipeptides) and can be reoxidized at the expense of molecular oxygen by
      producing H(2)O(2). This reaction mechanism, which differs from those already
      described for the formation of alpha,beta-dehydro-amino acids, might consist of
      the transient formation of an intermediate imine followed by its rearrangement
      into an alpha,beta-dehydro-residue.

PMID- 11248692
TI  - The structure of the core region of the lipopolysaccharide from Klebsiella
      pneumoniae O3. 3-deoxy-alpha-D-manno-octulosonic acid (alpha-Kdo) residue in the
      outer part of the core, a common structural element of Klebsiella pneumoniae O1,
      O2, O3, O4, O5, O8, and O12 lipopolysaccharides.
AB  - The structure of lipid A-core region of the lipopolysaccharide (LPS) from
      Klebsiella pneumoniae serotype O3 was determined using NMR, MS and chemical
      analysis of the oligosaccharides, obtained by mild acid hydrolysis, alkaline
      deacylation, and deamination of the LPS: [carbohydrate structure see text] where
      P is H or alpha-Hep; J is H or beta-GalA; R is H or P (in the deacylated
      oligosaccharides). Screening of the LPS from K. pneumoniae O1, O2, O4, O5, O8,
      and O12 using deamination showed that they also contain alpha-Hep-(1-->4)-alpha
      Kdo-(2-->6)-GlcN and alpha-Kdo-(2-->6)-GlcN fragments.

PMID- 11248693
TI  - Generation of human high-affinity antibodies specific for the fibroblast
      activation protein by guided selection.
AB  - Four completely human antibody derivatives [single-chain-antibody fragments
      (scFvs)] with specificity for the general tumor stroma marker fibroblast
      activation protein (FAP) were isolated by guided selection. Highly diverse IgG,
      IgM and IgD isotypes comprising heavy-chain variable domain libraries were
      generated using cDNAs derived from diverse lymphoid organs of a multitude of
      donors. Three of the human scFvs were converted into bivalent minibodies and
      expressed in eukaryotic cells for further functional characterization. Binding
      competition studies and analysis by fluorescence-activated cell sorting showed
      high-affinity binding (10--20 nM) for two clones and recognition of the same
      epitope as the murine guiding antibody. The minibodies were successfully used for
      immunohistology of a variety of human carcinoma biopsies, revealing specific
      staining of stromal fibroblasts. Therefore, they should be suitable for in vivo
      diagnostic and tumor-targeting studies and, because of their completely human
      origin, be superior to murine or humanized antibody derivatives.

PMID- 11248694
TI  - Structural and functional properties of Escherichia coli-derived nucleoplasmin. A
      comparative study of recombinant and natural proteins.
AB  - Fourier transform infrared spectroscopy, circular dichroism and prediction
      techniques have been used to investigate the conformational properties of
      nucleoplasmin isolated from oocytes and eggs of Xenopus. laevis and overexpressed
      in Escherichia coli. A simple and fast method allows purification of recombinant
      nucleoplasmin free of truncated and/or aggregated forms, and therefore provides a
      suitable sample to carry out the structural and functional comparison between
      these proteins. The secondary structure of the three proteins estimated from both
      spectroscopic techniques was very similar, and was found to be 31--33% loops, 27-
      34% beta structure, 22--26% turns and 9-14% alpha helix. Prediction studies, in
      good agreement with experimental data, also suggest that beta structure is the
      major regular conformation, and that loops and turns are the most abundant
      conformational features within the secondary structure of nucleoplasmin.
      Furthermore, the spectroscopic characterization of a truncated version of the
      protein, lacking 80 residues at the C-terminus, and the prediction data indicate
      that the secondary structure elements of the protein are segregated into two
      regions. The N-terminal fragment (comprising residues 1--120) which holds all the
      putative beta strands, and the solvent-exposed C-terminal region, that is
      suggested to be enriched in turn and loop structures. The phosphate/protein
      monomer molar ratios, obtained from chemical analysis and mass spectrometry, are
      0, 3 and 7--10 for recombinant, oocyte and egg nucleoplasmin, respectively.
      Phosphorylation does not significantly affect the secondary structure of the
      protein, but clearly modulates its ability to decondense sperm nuclei and to
      remove basic proteins from DNA.

PMID- 11248695
TI  - Organization and regulation of the rat Cx31 gene. Implication for a crucial role
      of the intron region.
AB  - The connexin31 (Cx31) gene, a member of the connexin multigene family, is
      expressed in a characteristic spatiotemporal pattern during placental development
      in rodents. To elucidate the trophoblast-specific regulation of Cx31, we have
      isolated the rat Cx31 gene and performed structural and functional promoter
      analysis. The isolated Cx31 gene contains two exons separated by an intron of 2.6
      kb. The first exon of the Cx31 gene is preceded by a TATA-less promoter region.
      Transcription is initiated in exon 1 from two transcription start sites
      producting transcripts of 105 and 139 bp. The 935 bp of the 5' flanking region of
      exon 1 comprises five putative binding sites for the GATA transcription factors
      as well as a NF-kappa B element, a CAAT-box and E-box/E-box-related sequences.
      For functional promoter analysis, the rat choriocarcinoma cell line Rcho-1 and
      the mouse keratinocyte cell line Hel37, which both express Cx31, were chosen.
      Only constructs including exon 1 and the complete intron showed high activity in
      transient transfection experiments in both cell lines. All deletion fragments of
      the putative promoter region, but which contain the entire intron sequence, did
      not reveal any obvious changes in luciferase activity. However, deletion of 1.1
      kb of the intron sequence downstream of the splice donor site resulted in the
      loss of promoter activity. The intron exhibits no enhancer activity for the gene;
      however, the mRNA stability was increased in the presence of the intron sequence.
      These results indicate that parts of the intron sequence are critical for basic
      promoter function of the Cx31 gene.

PMID- 11248696
TI  - Purification and characterization of the first archaeal aconitase from the
      thermoacidophilic Sulfolobus acidocaldarius.
AB  - The first archaeal aconitase was isolated from the cytosol of the
      thermoacidophilic Sulfolobus acidocaldarius. Interestingly, the enzyme was
      copurified with an isocitrate lyase. This enzyme, directly converting isocitrate,
      the reaction product of the aconitase reaction, was also unknown in
      crenarchaeota, thus far. Both proteins could only be separated by SDS gel
      electrophoresis yielding apparent molecular masses of 96 kDa for the aconitase
      and 46 kDa for the isocitrate lyase. Despite of its high oxygen sensitivity, the
      aconitase could be enriched 27-fold to a specific activity of approximately 55
      micromol x min(-1) x mg(-1), based on the direct aconitase assay system. Maximal
      enzyme activities were measured at pH 7.4 and the temperature optimum for the
      archaeal enzyme was recorded at 75 degrees C, slightly under the growth optimum
      of S. acidocaldarius around 80 degrees C. Thermal inactivation studies of the
      aconitase revealed the enzymatic activity to be uninfluenced after one hour
      incubation at 80 degrees C. Even at 95 degrees C, a half-life of approximately 14
      min was determined, clearly defining it as a thermostable protein. The apparent
      K(m) values for the three substrates cis-aconitate, citrate and isocitrate were
      found as 108 microM, 2.9 mM and 370 microM, respectively. The aconitase reaction
      was inhibited by the typical inhibitors fluorocitrate, trans-aconitate and
      tricarballylate. Amino-acid sequencing of three internal peptides of the S.
      acidocaldarius aconitase revealed the presence of highly conserved residues in
      the archaeal enzyme. By amino-acid sequence alignments, the S. acidocaldarius
      sequence was found to be highly homologous to either other putative archaeal or
      known eukaryal and bacterial sequences. As shown by EPR-spectroscopy, the enzyme
      hosts an interconvertible [3Fe--4S] cluster.

PMID- 11248697
TI  - Analysis of KdpC of the K(+)-transporting KdpFABC complex of Escherichia coli.
AB  - The Kdp complex, a high affinity ATP-driven K(+) transport system of Escherichia
      coli, is composed of the four membrane-bound subunits KdpF, KdpA, KdpB and KdpC.
      Whereas the role of KdpB (catalytical subunit), KdpA (K(+)-translocating subunit)
      and KdpF (stabilizing peptide) is well understood, the function of KdpC is still
      unknown. Therefore, a kdpC deletion strain was constructed and complementation
      experiments were performed using different kdpC constructs. Truncations of the
      kdpC gene revealed that only one derivative, which lacks base pairs coding for
      the four C-terminal amino acids, was able to complement the chromosomal deletion
      of kdpC. Furthermore, complementation was also observed with kdpC of
      Mycobacterium tuberculosis, but not with kdpC from Clostridium acetobutylicum or
      Synechocystis sp. PCC6803. Sequence alignment of 17 different KdpC proteins led
      to the construction of hybrids between kdpC of E. coli and that of C.
      acetobutylicum. Complementation revealed that the N-terminal transmembrane
      segment as well as the C-terminal-third of the protein can be exchanged between
      both species, but only one after the other. A simultaneous substitution of both
      regions was not possible.

PMID- 11248698
TI  - Response of native and denatured hen lysozyme to high pressure studied by
      (15)N/(1)H NMR spectroscopy.
AB  - High-pressure (15)N/(1)H NMR techniques were used to characterize the
      conformational fluctuations of hen lysozyme, in its native state and when
      denatured in 8 M urea, over the pressure range 30--2000 bar. Most (1)H and (15)N
      signals of native lysozyme show reversible shifts to low field with increasing
      pressure, the average pressure shifts being 0.069 +/- 0.101 p.p.m. ((1)H) and
      0.51 +/- 0.36 p.p.m. ((15)N). The shifts indicate that the hydrogen bonds formed
      to carbonyl groups or water molecules by the backbone amides are, on average,
      shortened by approximately 0.02 A as a result of pressure. In native lysozyme,
      six residues in the beta domain or at the alpha/beta domain interface have
      anomalously large nonlinear (15)N and (1)H chemical-shift changes. All these
      residues lie close to water-containing cavities, suggesting that there are
      conformational changes involving these cavities, or the water molecules within
      them, at high pressure. The pressure-induced (1)H and (15)N shifts for lysozyme
      denatured in 8 M urea are much more uniform than those for native lysozyme, with
      average backbone amide shifts of 0.081 +/- 0.029 p.p.m. ((1)H) and 0.57 +/- 0.14
      p.p.m. ((15)N). The results show that overall there are no significant variations
      in the local conformational properties of denatured lysozyme with pressure,
      although larger shifts in the vicinity of a persistent hydrophobic cluster
      indicate that interactions in this part of the sequence may rearrange. NMR
      diffusion measurements demonstrate that the effective hydrodynamic radius of
      denatured lysozyme, and hence the global properties of the denatured ensemble, do
      not change detectably at high pressure.

PMID- 11248699
TI  - Phenylmethanesulfonyl fluoride inactivates an archaeal superoxide dismutase by
      chemical modification of a specific tyrosine residue. Cloning, sequencing and
      expression of the gene coding for Sulfolobus solfataricus superoxide dismutase.
AB  - The gene encoding the superoxide dismutase from the hyperthermophilic archaeon
      Sulfolobus solfataricus (SsSOD) was cloned and sequenced and its expression in
      Escherichia coli obtained. The chemicophysical properties of the recombinant
      SsSOD were identical with those of the native enzyme. The recombinant SsSOD
      possessed a covalent modification of Tyr41, already observed in native SsSOD
      [Ursby, T., Adinolfi, B.S., Al-Karadaghi, S., De Vendittis, E. & Bocchini, V.
      (1999) J. Mol. Biol. 286, 189--205]. HPLC analysis of SsSOD samples prepared from
      cells treated or not with phenylmethanesulfonyl fluoride (PhCH(2)SO(2)F), a
      protease inhibitor routinely added during the preparation of cell-free extracts,
      showed that the modification was caused by PhCH(2)SO(2)F. Refinement of the
      crystal model of SsSOD confirmed that a phenylmethanesulfonyl moiety was attached
      to the hydroxy group of Tyr41. PhCH(2)SO(2)F behaved as an irreversible
      inactivator of SsSOD; in fact, the specific activity of both native and
      recombinant enzyme decreased as the percentage of modification increased. The
      covalent modification caused by PhCH2SO2F reinforced the heat stability of SsSOD.
      These results show that Tyr41 plays an important role in the enzyme activity and
      the maintenance of the structural architecture of SsSOD.

PMID- 11248700
TI  - Activator protein-1 is necessary for angiotensin-II stimulation of human
      adrenocorticotropin receptor gene transcription.
AB  - Previous studies have demonstrated that angiotensin-II (A-II) increases the human
      adrenocorticotropin receptor (hMC2R) gene expression in adrenal cells. In the
      present study, we have characterized two activator protein-1 (AP-1)-binding sites
      involved in the A-II stimulation of hMC2R gene transcription. Vectors containing
      different fragments of the hMC2R gene promoter inserted upstream of the
      luciferase gene, have been constructed. After transfection of H295R cells with
      these constructs and treatment of the cells by A-II during 48 h, maximal
      stimulation of the luciferase activity was obtained using the construct p(
      263/+22)luc. Using progressively deleted constructs, three regions responsible
      for the A-II-stimulated transcription of hMC2R have been delineated. Inside these
      regions, two sequences displayed some homology with an AP-1 binding element (AP
      108 and AP-203). Mutation of either AP-108 or AP-203 site induced a decrease of A
      II-stimulated luciferase activity by 40% and 25%, respectively. Gel-shift
      analysis showed protein binding to these sites which was increased by an A-II
      treatment (maximum obtained after 3 h). Moreover, A-II could rapidly increase
      mRNA levels of several factors belonging to the Fos and Jun families which may be
      components of the AP-1 complex.

PMID- 11248701
TI  - Differential control of gene activity by isoforms A, B1 and B2 of the Drosophila
      ecdysone receptor.
AB  - The steroid hormone ecdysone initiates molting and metamorphosis in Drosophila
      via a heterodimeric receptor consisting of EcR that binds hormone, and USP, a
      homolog of the vertebrate RXR receptor. EcR exists in three isoforms EcRA, EcRB1
      and EcRB2 that are thought to direct specific physiological responses to
      ecdysone. These three isoforms differ only in their N-terminal A/B domain that
      implies that sequences responsible for the differential physiological effects lie
      within the A/B domains of the EcR isoforms. In the present study, we set out to
      determine the capability of the three isoforms and their A/B domains to control
      gene transcription. When full-length EcR plasmids were cotransfected into
      mammalian cells with a USP expressing and a cognate reporter plasmid, the three
      EcR isoforms showed striking differences in their ability to control gene
      transcription, both in the presence and in the absence of hormone. Furthermore,
      the A/B domains of EcRB1 and of EcRB2 when fused to the GAL4 DNA binding domain
      are sufficient to activate transcription of a reporter gene, in yeast as well as
      in mammalian cells. In contrast, a fusion construct containing the A/B domain of
      EcRA represses basal transcription of the reporter gene. All these findings
      emphasize the importance of the A/B domains of the three EcR isoforms for
      differentially controlling gene transcription. Furthermore, they provide evidence
      for the existence of an autonomous ligand-independent activation function (AF1)
      in the A/B domains of EcRB1 and EcRB2 and of an inhibitory function (IF) in the
      A/B domain of EcRA.

PMID- 11248702
TI  - A third crystal form of Wolinella succinogenes quinol:fumarate reductase reveals
      domain closure at the site of fumarate reduction.
AB  - Quinol:fumarate reductase (QFR) is a membrane protein complex that couples the
      reduction of fumarate to succinate to the oxidation of quinol to quinone.
      Previously, the crystal structure of QFR from Wolinella succinogenes was
      determined based on two different crystal forms, and the site of fumarate binding
      in the flavoprotein subunit A of the enzyme was located between the FAD-binding
      domain and the capping domain [Lancaster, C.R.D., Kroger, A., Auer, M., & Michel,
      H. (1999) Nature 402, 377--385]. Here we describe the structure of W.
      succinogenes QFR based on a third crystal form and refined at 3.1 A resolution.
      Compared with the previous crystal forms, the capping domain is rotated in this
      structure by approximately 14 degrees relative to the FAD-binding domain. As a
      consequence, the topology of the dicarboxylate binding site is much more similar
      to those of membrane-bound and soluble fumarate reductase enzymes from other
      organisms than to that found in the previous crystal forms of W. succinogenes
      QFR. This and the effects of the replacement of Arg A301 by Glu or Lys by site
      directed mutagenesis strongly support a common mechanism for fumarate reduction
      in this superfamily of enzymes.

PMID- 11248703
TI  - Stimulation of the ICAM-1 gene transcription by the peroxovanadium compound
      [bpV(Pic)] involves STAT-1 but not NF-kappa B activation in 293 cells.
AB  - Vanadate and peroxovanadium derivatives are potent inhibitors of protein tyrosine
      phosphatases (PTPs) and exhibit insulinomimetic activities in several cell
      systems. We have found that in 293 and 293T cells, intercellular adhesion
      molecule-1 (ICAM-1) gene transcription is activated by bpV(Pic), a picolinic acid
      stabilized peroxovanadium derivative. To identify the bpV(Pic)-responsive
      element(s), several deletion and site-specific mutants of the ICAM-1 gene
      promoter cloned upstream from the firefly luciferase reporter gene were
      transiently transfected into both cell lines. Deletion or site-specific mutation
      of the NF-kappa B site did not affect bpV(Pic) responsiveness, whereas deletion
      or mutation of the palindromic interferon-gamma-responsive element (pI gamma
      RE)/gamma-interferon activated sequence site greatly decreased bpV(Pic)
      responsiveness in both cell types. bpV(Pic) synergistically co-operated with
      interferon-gamma to increase the transcriptional activity of the ICAM-1 promoter.
      Electrophoretic mobility-shift assays showed that bpV(Pic) induces signal
      transducers and activators of transcription (STAT)-1 binding to the ICAM-1 pI
      gamma RE/GAS in 293T cells, suggesting that the peroxovanadium compound
      specifically inhibits the phosphatase(s) required to regulate the JAK/STAT signal
      transduction pathway.

PMID- 11248704
TI  - Covalently crosslinked complexes of bovine adrenodoxin with adrenodoxin reductase
      and cytochrome P450scc. Mass spectrometry and Edman degradation of complexes of
      the steroidogenic hydroxylase system.
AB  - NADPH-dependent adrenodoxin reductase, adrenodoxin and several diverse
      cytochromes P450 constitute the mitochondrial steroid hydroxylase system of
      vertebrates. During the reaction cycle, adrenodoxin transfers electrons from the
      FAD of adrenodoxin reductase to the heme iron of the catalytically active
      cytochrome P450 (P450scc). A shuttle model for adrenodoxin or an organized
      cluster model of all three components has been discussed to explain electron
      transfer from adrenodoxin reductase to P450. Here, we characterize new covalent,
      zero-length crosslinks mediated by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide
      between bovine adrenodoxin and adrenodoxin reductase, and between adrenodoxin and
      P450scc, respectively, which allow to discriminate between the electron transfer
      models. Using Edman degradation, mass spectrometry and X-ray crystallography a
      crosslink between adrenodoxin reductase Lys27 and adrenodoxin Asp39 was detected,
      establishing a secondary polar interaction site between both molecules. No
      crosslink exists in the primary polar interaction site around the acidic residues
      Asp76 to Asp79 of adrenodoxin. However, in a covalent complex of adrenodoxin and
      P450scc, adrenodoxin Asp79 is involved in a crosslink to Lys403 of P450scc. No
      steroidogenic hydroxylase activity could be detected in an adrenodoxin -P450scc
      complex/adrenodoxin reductase test system. Because the acidic residues Asp76 and
      Asp79 belong to the binding site of adrenodoxin to adrenodoxin reductase, as well
      as to the P450scc, the covalent bond within the adrenodoxin-P450scc complex
      prevents electron transfer by a putative shuttle mechanism. Thus, chemical
      crosslinking provides evidence favoring the shuttle model over the cluster model
      for the steroid hydroxylase system.

PMID- 11248705
TI  - Expression of cardiotoxin-2 gene. Cloning, characterization and deletion analysis
      of the promoter.
AB  - This report is the first study of the regulation of expression of a toxin gene
      and it also demonstrates the novel finding that the cardiotoxin (CTX)-2 gene from
      Naja sputatrix is expressed in the venom gland as well as in other tissues in the
      snake, such as liver, heart and muscle. The venom gland produces a 500-bp
      (spliced) CTX-2 mRNA as the final transcript. However, the liver produces two
      types of CTX-2 mRNA, of which the unspliced transcript (1 kb) is predominant; the
      500 bp spliced transcript is the minor species. This differential expression of
      the CTX gene has been attributed to the usage of alternative promoter consisting
      of independent TATA boxes and corresponding transcription initiation sites. Among
      the several transcription factors that have been identified by a search of the
      TFIID database, the participation of two glucocorticoid elements in the
      expression of the CTX gene has been demonstrated by promoter deletion analysis.
      Putative binding sites for SP-1, C/EBP, CACCC-binding factor and at least two
      unknown binding factors have also been identified by DNase I footprinting of the
      promoter.

PMID- 11248706
TI  - Incomplete refolding of a fragment of the N-terminal domain of pig muscle 3
      phosphoglycerate kinase that lacks a subdomain. Comparison with refolding of the
      complementary C-terminal fragment.
AB  - Refolding of pig muscle 3-phosphoglycerate kinase (PGK) from a mixture of its
      complementary proteolytic fragments that did not correspond to the individual
      domains resulted in a high degree of reactivation [Vas, M., Sinev, M.A., Kotova,
      N. & Semisotnov, G.V. (1990) Eur. J. Biochem. 189, 575--579]. An independent
      refolding of the 27.7 kDa C-terminal proteolytic fragment (which encompasses the
      whole C domain) has been noted, but the refolding ability of the 16.8-kDa N
      terminal proteolytic fragment, which lacks a single subdomain from the N domain,
      remained to be seen. Here the refolding processes of the isolated fragments are
      compared. Within the first few seconds of initiation of refolding, pulse
      proteolysis experiments show the formation of a structure with moderate protease
      resistance for both fragments. This structure, however, remains unchanged upon
      further incubation of the N-terminal fragment, whereas refolding of the C
      terminal fragment continues as detected by a further increase in proteolytic
      resistance. The non-native character of the folding intermediate of the N
      fragment is indicated by the elevated fluorescence intensity of the bound
      hydrophobic probe 8-anilino-1-naphtalene sulphonate. Its CD spectrum shows the
      formation of secondary structure distinct from the native one. The noncooperative
      phase-transition observed in microcalorimetry indicates the absence of a rigid
      tertiary structure, in contrast with the refolded C-terminal fragment for which a
      cooperative transition is seen. Size-exclusion chromatography supported the
      globular character of the intermediate, and showed its propensity to form dimers.
      No binding of the substrate, 3-phosphoglycerate (3-PGri), to the isolated N
      terminal fragment, could be detected but the presence of the complementary C
      terminal fragment led to restoration of the substrate binding ability of the N
      domain. Thus, refolding of the isolated N-terminal fragment yields a highly
      flexible, globular, potentially productive intermediate with non-native secondary
      structure and highly exposed hydrophobic clusters, which favour dimerization.

PMID- 11248707
TI  - Recombinant expression of N-terminal truncated mutants of the membrane bound
      mouse, rat and human flavoenzyme dihydroorotate dehydrogenase. A versatile tool
      to rate inhibitor effects?
AB  - Mammalian dihydroorotate dehydrogenase, the fourth enzyme of pyrimidine de novo
      synthesis is an integral protein of the inner mitochondrial membrane that faces
      the intermembrane space and is functionally connected to the respiratory chain
      via ubiquinone. Here, we describe the first cloning and analyzing of the complete
      cDNA of mouse dihydroorotate dehydrogenase. Based on our recent functional
      expression of the full-length rat and human dihydroorotate dehydrogenase, here we
      expressed N-terminal-truncated C-terminal-histidine-tagged constructs of the
      mouse, rat and human enzymes in Escherichia coli. These proteins were devoid of
      the N-terminal bipartite sequence consisting of the mitochondrial targeting
      sequence and adjacent hydrophobic domain necessary for import and proper location
      and fixation of the enzyme in the inner mitochondrial membrane. By employing
      metal-chelate affinity chromatography under native conditions, the enzymes were
      purified without detergents to a specific activity of more than 100 micromol x
      min(-1) x mg(-1) at pH optimum of 8.0--8.1. Flavin analyses by UV-visible
      spectrometry of the native enzymes gave fairly stoichiometric ratios of 0.6--1.2
      mol flavin per mol protein. The kinetic constants of the truncated rat enzyme
      (K(m) = 11 microM dihydroorotate; K(m) = 7 microM ubiquinone) and human enzyme
      (K(m) = 10 microM dihydroorotate; K(m) = 14 microM ubiquinone) were very close to
      those recently reported for the full-size enzymes. The constants for the mouse
      enzyme, K(m) = 26 microM dihydroorotate and K(m) = 62 microM ubiquinone, were
      slightly elevated in comparison to those of the other species. The three
      truncated enzymes were tested for their efficacy with five inhibitors of topical
      clinical relevance against autoimmune disorders and tumors. Whereas the presence
      of the N-terminus of dihydroorotate dehydrogenase was essentially irrelevant for
      the efficacy of the malononitrilamides A77-1726, MNA715 and MNA279 with the rat
      and human enzyme, the N-termini were found to be important for the efficacy of
      the dianisidine derivative redoxal. Moreover, the complete N-terminal part of the
      human enzyme seemed to be of crucial importance for the 'slow-binding' features
      of the cinchoninic acid derivative brequinar, which was suggested to be one of
      the reasons for the narrow therapeutic window reported from clinical trials on
      its anti-proliferative and immunosuppressive action.

PMID- 11248708
TI  - Characterization of PknC, a Ser/Thr kinase with broad substrate specificity from
      the cyanobacterium Anabaena sp. strain PCC 7120.
AB  - Eukaryotic-like protein Ser/Thr and Tyr kinases have only recently been
      discovered in prokaryotes. In most cases, their biochemical properties have been
      poorly characterized. The nitrogen-fixing and heterocyst-forming cyanobacterium
      Anabaena sp. strain PCC 7120 houses a family of eukaryotic-like Ser/Thr kinases.
      Some of these enzymes are required for cell growth or development under certain
      conditions. None of them, however, has been shown experimentally to possess
      Ser/Thr kinase activity. A gene, pknC, encoding a novel putative Ser/Thr kinase
      was isolated from Anabaena sp. PCC 7120. The recombinant PknC was shown to be
      phosphorylated on a Thr residue. This phosphorylation was probably due to the
      autophosphorylation activity of PknC itself because mutation of two amino acid
      residues within the subdomain II of its catalytic domain eliminated the
      phosphorylation of PknC. PknC displayed also a Ser kinase activity towards
      several nonspecific substrates, and the two residues needed for PknC
      autophosphorylation was equally required for the phosphorylation of other
      substrates. PknC is thus a Ser/Thr kinase with broad substrate specificity. The
      activity of PknC is likely to be regulated in vivo in order to limit the spectrum
      of its substrate specificity.

PMID- 11248709
TI  - Development and characterization of an animal model of carnitine deficiency.
AB  - Mammals cover their carnitine needs by diet and biosynthesis. The last step of
      carnitine biosynthesis is the conversion of butyrobetaine to carnitine by
      butyrobetaine hydroxylase. We investigated the effect of N-trimethyl-hydrazine-3
      propionate (THP), a butyrobetaine analogue, on butyrobetaine hydroxylase
      kinetics, and carnitine biosynthesis and body homeostasis in rats fed a casein
      based or a vegetarian diet. The K(m )of butyrobetaine hydroxylase purified from
      rat liver was 41 +/- 9 micromol x L(-1) for butyrobetaine and 37 +/- 5 micromol x
      L(-1) for THP, and THP was a competitive inhibitor of butyrobetaine hydroxylase
      (K(i) 16 +/- 2 micromol x L(-1)). In rats fed a vegetarian diet, renal excretion
      of total carnitine was increased by THP (20 mg.100 g(-1) x day(-1) for three
      weeks), averaging 96 +/- 36 and 5.3 +/- 1.2 micromol x day(-1) in THP-treated and
      control rats, respectively. After three weeks of treatment, the total carnitine
      plasma concentration (8.8 +/- 2.1 versus 52.8 +/- 11.4 micromol x L(-1)) and
      tissue levels were decreased in THP-treated rats (liver 0.19 +/- 0.03 versus 0.59
      +/- 0.08 and muscle 0.24 +/- 0.04 versus 1.07 +/- 0.13 micromol x g(-1)).
      Carnitine biosynthesis was blocked in THP-treated rats (-0.22 +/- 0.13 versus
      0.57 +/- 0.21 micromol x 100 g(-1) x day(-1)). Similar results were obtained in
      rats treated with the casein-based diet. THP inhibited carnitine transport by rat
      renal brush-border membrane vesicles competitively (K(i) 41 +/- 3 micromol x L(
      1)). Palmitate metabolism in vivo was impaired in THP-treated rats and the livers
      showed mixed steatosis. Steady-state mRNA levels of the carnitine transporter rat
      OCTN2 were increased in THP-treated rats in skeletal muscle and small intestine.
      In conclusion, THP inhibits butyrobetaine hydroxylase competitively, blocks
      carnitine biosynthesis in vivo and interacts competitively with renal carnitine
      reabsorption. THP-treated rats develop systemic carnitine deficiency over three
      weeks and can therefore serve as an animal model for human carnitine deficiency.

PMID- 11248710
TI  - The role of exon 5 in fibroblast collagenase (MMP-1) substrate specificity and
      inhibitor selectivity.
AB  - Interstitial collagen is degraded by members of the matrix metalloproteinase
      (MMP) family, including MMP-1. Previous work has shown that the region of MMP-1
      coded for by exon 5 is implicated both in substrate specificity and inhibitor
      selectivity. We have constructed a chimeric enzyme, the exon 5 chimera,
      consisting primarily of MMP-1, with the region coded for by exon 5 replaced with
      the equivalent region of MMP-3, a noncollagenolytic MMP. Unlike MMP-3, the exon 5
      chimera is capable of cleaving type I collagen, but the activity is only 2.2% of
      trypsin-activated MMP-1. 'Superactivation' of the chimera has no discernible
      effect, suggesting that the salt bridge formed in 'superactive' MMP-1 is not
      present. The kinetics for exon 5 chimera cleavage of two synthetic substrates
      display an MMP-3 phenotype, however, cleavage of gelatin is slightly impaired as
      compared to the parent enzymes. The K(iapp) values for the exon 5 chimera
      complexed with synthetic inhibitors and N-terminal TIMP-2 also show a more MMP-3
      like behaviour. However, the k(on) values for N-terminal TIMP-1 and N-terminal
      TIMP-2 are more comparable to those for MMP-1. These data show that the region of
      MMP-1 coded for by exon 5 is involved in both substrate specificity and inhibitor
      selectivity and the structural basis for our findings is discussed.

PMID- 11248711
TI  - Women and heart failure.
AB  - Almost half of the patients affected with congestive heart failure (CHF) in the
      United States are women. However, past studies have included predominantly men
      and generalized results to women. Many women with CHF are older, have
      hypertension, and have higher ejection fractions. Survival differences have been
      reported previously with conflicting results. Although treatment for left
      ventricular dysfunction is somewhat standardized, treatment for diastolic
      dysfunction is less defined. Clinical trials for this group of patients, many of
      whom are women, have not been performed. In comparison with men, women have
      several cardiovascular differences as well as differences in electrical
      properties. In addition, response to medical (pharmacologic) therapy may differ
      in men and women.Finally, functional status has been shown to be compromised in
      both men and women with CHF; however, some studies have shown women to experience
      more exercise intolerance. This may be because more women than men have diastolic
      dysfunction. Few women have been included in exercise trials. Future trials must
      address women with CHF, many of whom are older and have normal (or near normal)
      left ventricular function or diastolic dysfunction.

PMID- 11248712
TI  - Relationship of physical symptoms and physical functioning to depression in
      patients with heart failure.
AB  - OBJECTIVE: The purpose of this study was to determine the relative contribution
      of physical symptoms and physical functioning to depression in adult patients
      with heart failure during hospitalization and the early postdischarge period.
      DESIGN: An exploratory, correlational longitudinal design was used. PATIENTS: The
      sample included 170 subjects with heart failure. RESULTS: Subjects' mean scores
      on the depression scale indicated that subjects were not depressed on average;
      however, 30% of the sample (n = 52) had scores indicative of clinical depression.
      Both physical symptoms (r = 0.48) and physical functioning (r = -0.32) were
      moderately correlated with depression. Physical symptoms contributed 13% uniquely
      to the variance in depression while physical functioning contributed only 2%
      uniquely to the variance in depression. Multiple regression analyses indicated
      that physical symptomatology is more closely related to depression than is
      physical functioning in adults with heart failure. CONCLUSIONS: This study showed
      the patients with heart failure who had increased physical symptoms and poorer
      physical functioning reported increased symptoms of depression. Physical symptoms
      explained a greater portion of the variance in depression than did physical
      functioning. Thus, it appears that patients with heart failure are affected
      emotionally by both their physical symptoms and their limitations in their
      physical functioning, but depression is more strongly related to having more
      physical symptoms than having greater limitations in physical functioning.

PMID- 11248713
TI  - Quality of life in patients with heart failure: do gender differences exist?
AB  - OBJECTIVE: The purpose of this study was to evaluate gender differences in
      quality of life (QOL) in a large sample of age-matched and ejection fraction (EF)
      matched patients with heart failure. DESIGN: Matched comparisons of secondary
      data were used. SETTING: The setting consisted of multicenter Studies of Left
      Ventricular Dysfunction trials. SAMPLE: The sample included 1382 patients (691
      men and 691 women) who were age-matched and EF-matched. OUTCOME MEASURES: Global
      QOL and the QOL dimensions of physical function, emotional distress, social
      health, and general health were measured using the Ladder of Life, items from the
      Profile of Mood States Inventory, the Functional Status Questionnaire, the beta
      Blocker Heart Attack Trial instrument, and an item from the RAND Medical Outcomes
      Study instrument. RESULTS: Women had significantly worse general life
      satisfaction, physical function, and social and general health scores than men.
      There were no significant differences found between gender groups for current
      life situation or emotional distress. After controlling for New York Heart
      Association classification, women still had significantly worse ratings for
      intermediate activities of daily living (a sub-dimension of physical functioning)
      and social activity. CONCLUSIONS: Despite controlling for age, EF, and New York
      Heart Association classification, women had worse QOL ratings than did men for
      intermediate activities of daily living and social activity. Research should
      focus on identifying why differences exist and developing measures to improve
      QOL, particularly physical functioning, in women with heart failure.

PMID- 11248714
TI  - Women's perceptions of their social roles after heart surgery and coronary
      angioplasty.
AB  - OBJECTIVE: The goal of this study was to describe the influence of physical
      health on social role perceptions, role performance, and role balance in women
      after heart surgery and coronary angioplasty. DESIGN: A cross-sectional
      descriptive survey was used. SETTING: The study was undertaken at a Midwestern
      community hospital. SAMPLE: The study considered 58 midlife and older women who
      had received heart surgery or coronary angioplasty. OUTCOME MEASURES: The
      following measures were used: Inventory of Adult Role Behavior, Role Discrepancy
      Measure, Role Balance Measure, and Salient Social Roles Measure. RESULTS: Women
      in poorer health had lower role performance and more negative role perceptions.
      In general, the balance of rewards and concerns in roles rated most important
      were not affected by health status. CONCLUSION: Dimensions of women's social
      roles are related to physical health after heart surgery and angioplasty.
      Knowledge about the effect of physical health on women's social role experiences
      is important information for clinicians who care for women with heart disease. If
      a woman can be helped to achieve better functional health to perform role and
      daily living tasks, she may feel more positive about her current and future
      health states.

PMID- 11248715
TI  - Factors associated with participation in a mitral valve prolapse support group.
AB  - PURPOSE: The goal of this study was to explore factors that may influence
      attendance at a mitral valve prolapse (MVP) support group. DESIGN: The study
      design was nonexperimental and descriptive. METHOD: The MVP Support Group
      Questionnaire was mailed to 18 MVP support group leaders and to 700 persons in
      whom MVP had been diagnosed. FINDINGS: Three hundred seventy-six questionnaires
      were analyzed. Data demonstrate that persons more likely to participate in an MVP
      support group are those who are older (>50 years of age) and those who belong to
      other self-help groups. The most important reason for attending these support
      groups was to obtain more information about MVP. CONCLUSIONS: Data suggest that
      MVP support groups are needed to provide support and information to people with
      MVP syndrome-information that is not normally available from family, friends, and
      physicians.

PMID- 11248716
TI  - Coronary angiography observations: evidence-based or ritualistic practice?
AB  - OBJECTIVE: The purposes of this study were to describe the incidence and
      occurrence of femoral artery bleeding during the first 6 hours after coronary
      angiography and to determine whether there is a relationship between current
      postangiogram observation protocols and the detection of complications. DESIGN:
      This was a prospective descriptive study. SETTING: The study was conducted in 3
      university hospitals in Melbourne, Australia. PATIENTS: Subjects included 55
      patients representing the complication rate of 1075 patients, mean age 61 years
      (SD, 12), 69% male. RESULTS: About 5.1% of patients had 1 or more incidents of
      bleeding requiring manual compression. In 4.2% of patients, bleeding occurred
      within 6 hours of angiography. Bleeding occurred a median of 2.02 hours (Q1 = 45
      minutes, Q3 = 4.31 hours) after angiography. Patients without pressure bandaging
      bled a median of 1.32 hours (Q1 = 36.50 minutes, Q3 = 2.59 hours) after
      angiography. Patients with pressure bandaging bled a median of 4.75 hours (Q1 =
      2.25 hours, Q3 = 7.28 hours) after angiography. In 40.6% of cases, bleeding was
      detected through the patient's call for assistance, and in 59.4% of cases nurses
      noted bleeding while checking the puncture site. Postcatheter observations were
      recorded 23.70 (SD, 14.60) minutes before the bleeding incident. There were no
      significant changes in vital signs, systolic blood pressure (P >.05), diastolic
      blood pressure (P >.05), or pulse (P >.05) before or during a bleeding episode.
      All were within normal parameters. No neurovascular assessment anomalies were
      detected. CONCLUSION: The use of pressure bandaging has a significant effect on
      the incidence and pattern of bleeding. Routine vital sign measurement has no
      relevance in detecting local complications after angiography. The most
      significant complication is bleeding that requires manual compression. Detection
      is through frequent puncture site observation and patient recognition and
      communication.

PMID- 11248717
TI  - Safety and efficacy of heliox as a treatment for upper airway obstruction due to
      radiation-induced laryngeal dysfunction.
AB  - The mixture of helium and oxygen, called heliox, has been successfully used in
      the management of different respiratory diseases since 1935. Despite several
      reports on its usefulness, it is not widely available in acute care facilities
      and it remains somewhat controversial. In this article we present the case of a
      69-year-old woman in whom bilateral vocal cord paralysis developed after
      radiation therapy and in whom heliox was successfully used to manage her upper
      airway obstruction. Although heliox offers an additional tool in the treatment of
      various airway and pulmonary problems, it can be used only as a temporizing agent
      to allow time for appropriate therapy of the underlying process. Given its
      beneficial physiologic and clinical effects, it seems that further studies are
      warranted to define a clear and concise protocol for its use in the emergency
      setting.

PMID- 11248719
TI  - Puncture wound during CPR from sternotomy wires: case report and discussion of
      periresuscitation infection risks.
AB  - Performing resuscitations presents multiple infectious risks to critical care
      providers. Potential sources for infection include direct contact with blood and
      other bodily fluids and possible inoculation through needlestick injuries. In
      this article, we present a case of a cardiac care unit nurse who, while providing
      cardiopulmonary resuscitation, suffered a puncture wound to her left hand from
      the patient's sternotomy wires from previous cardiac surgery. The patient died
      despite these resuscitation efforts. He was seronegative for human immunodefiency
      virus, hepatitis B, and hepatitis C, and the nurse's wound healed without
      complications. This is the first reported case of such an injury occurring during
      a resuscitation. It demonstrates how a subtle, invisible, and unrecognized
      physical risk could cause infection in critical care providers.

PMID- 11248718
TI  - Smoking cessation in the hospitalized patient using the transtheoretical model of
      behavior change.
AB  - Tobacco use continues to be the most prevalent cause of preventable morbidity and
      mortality in the United States, causing more than 430,000 deaths each year, or 1
      in every 5 deaths. In addition, many health care providers employed in critical
      care settings deal with patients who have experienced a near-death event that has
      led them to consider smoking cessation. The smoking cessation rate 1 year after a
      myocardial infarction is approximately 70% in those patients who receive a
      smoking cessation intervention. Theory-based smoking cessation interventions have
      been found to be effective. The purpose of this article is to present the
      transtheoretical model as basis for developing a hospital-based smoking cessation
      intervention. In addition, symptom management options will be discussed.

PMID- 11248720
TI  - Electrocardiographic changes in hypothermia.
AB  - With the clinical use of cold cardioplegia, or total body hypothermia, it is
      crucial that critical care physicians and nurses be aware of the
      electrocardiographic changes related to hypothermia. Similar changes also occur
      with accidental exposure to cold. We report and discuss a patient who presented
      with typical electrocardiographic changes upon accidental exposure to cold.

PMID- 11248721
TI  - Dyspnea near the end of life: an excerpt from the upcoming RNS 11th Annual
      Conference.

PMID- 11248722
TI  - Re: a pilot study exploring mood state and dyspnea in mechanically ventilated
      patients.

PMID- 11248724
TI  - Kudos and reflections.

PMID- 11248725
TI  - A new section, a new section editor.

PMID- 11248726
TI  - Caffeine and urinary continence.

PMID- 11248727
TI  - Qualitative research: a different paradigm--part 1.

PMID- 11248728
TI  - A critical review of the literature: part I: diagnosing osteomyelitis in patients
      with diabetes and foot ulcers.
AB  - Despite our best efforts, chronic wounds continue to confound us. Cases of
      patients with diabetes who have wounds are particularly perplexing and
      challenging to manage. The diagnosis and treatment of osteomyelitis in this
      population are of great interest to clinicians. Much of wound care is based on
      tradition and expert opinion. The current focus is on evidence-based practice.
      The purpose of this critical literature review is to determine the best evidence
      for diagnosing osteomyelitis as a basis for providing appropriate therapy to
      patients with diabetes and foot ulcers. Treatments vary greatly in terms of time,
      cost, and invasiveness depending on the accuracy of the diagnosis. The choice of
      oral versus parenteral antibiotics, the length of the treatment, and decisions
      about surgical intervention or aggressive debridement are based on correctly
      differentiating osteomyelitis from soft tissue infection, osteoarthropathy, and
      other conditions. It is difficult to differentiate soft tissue infection from
      bone infection in the patient with diabetes and neuropathic bone disease. The
      precision of available tools for diagnosing osteomyelitis in patients with
      diabetes and foot ulcers is widely debated. A gold standard as a reference test
      for clinical trials and treatment decisions has not been consistently used in
      published research studies. Without a reference test that is reliable and valid,
      the conclusions regarding effectiveness of diagnostic modalities and antibiotic
      treatment regimens are questionable.

PMID- 11248729
TI  - Use of telehealth for chronic wound care: a case study.
AB  - Use of telehealth in wound care continues to expand as technology is enhanced and
      clinicians become more familiar with use of the new technology as a supplement to
      usual care. This article describes the Telehealth Wound Care Program implemented
      at Mount Sinai Hospital Home Health Agency and Mount Sinai Hospital Wound Care
      Center. Results of the wound care provided for one patient are included in the
      case study described in this article. The authors note the many benefits of
      telehealth as an adjunct to usual therapy in wound care.

PMID- 11248730
TI  - Living with an ostomy and short bowel syndrome: practical aspects and impact on
      daily life.
AB  - PURPOSE: Practical aspects and impact on daily life of short bowel syndrome (SBS)
      and an ostomy were explored in people with SBS. Interest was focused on nutrition
      and excretion, ostomy problems, associated medical and surgical problems,
      socioeconomic situation, and social and leisure activities. SUBJECTS AND SETTING:
      Six subjects (range, 38-68 years) with Crohn's disease were included from the
      University Short Bowel Clinic at Sahlgrenska University Hospital, Gothenburg,
      Sweden. Average disease duration was 25 years, and mean small intestinal length
      was 107 cm; 4 subjects were receiving parenteral nutrition at home. METHODS:
      Subjects were interviewed in their homes using a semistructured interview divided
      into the areas of focus. Data were transcribed by shorthand and were rewritten
      into the computer the same day. A questionnaire on nutrition and excretion was
      answered by the subjects in writing and mailed to the interviewer. RESULTS: The
      most significant observation was the limited ability to act spontaneously,
      because all daily activities involved considerable planning. Three subjects said
      they had never accepted the ostomy; the others would not return to their pre
      stoma lifestyle. The 2 subjects with a colostomy described special emptying
      patterns that caused limitations in social life that had not been reported
      previously. Fistulas were reported as having been the most trying part of the
      disease. Three subjects worked part time, which was of utmost importance for
      quality of life. Fatigue influenced social and leisure activities. CONCLUSION:
      People with SBS are bothered by a number of demanding problems in various aspects
      of life. Therefore, a team approach toward care is critical to allow for
      coordination of action toward the various needs. It also seems unlikely that
      standard instruments of quality of life can capture the complicated situations
      with which these subjects live. It appears that coping mechanisms also need to be
      considered.

PMID- 11248731
TI  - The CPE network: creating an evidence base for continence product selection.
AB  - Selecting continence products for an individual patient or hospital contract is
      often a daunting task. This article describes the evaluation process developed
      for a program of government-funded multicenter evaluations of continence products
      established in the United Kingdom to provide an evidence base for product
      selection. The essential requirements of an evaluation are discussed, together
      with the methodologic and statistical issues that such evaluations present. The
      strengths and limitations of multicenter trials are examined and suggestions are
      made regarding other areas of nursing in which this approach could be usefully
      adopted.

PMID- 11248732
TI  - Stoma site selection in a patient with multiple enterocutaneous fistulae.

PMID- 11248735
TI  - Testosterone levels in healthy men and the relation to behavioural and physical
      characteristics: facts and constructs.
AB  - This review summarises the correlations between testosterone levels and male
      physical appearance and behaviour. Methodological shortcomings concerning the
      measurement of testosterone could limit the value of these findings. In addition,
      testosterone measured in body fluids represents only one step in the cascade of
      action from production to biological effect, and could therefore provide only a
      limited view of the complexity of physiological events. Testosterone levels are
      influenced by conditions that are partly controlled or initiated by the hormone
      itself, but also by circumstances beyond hormonal or individual control.
      Different kinds of behaviour are not only subject to influence by environment,
      but also androgens can reinforce the particular kind of conduct and the
      behavioural impact can wield negative or positive feedback on testosterone
      secretion. Therefore, both generalisation and individualisation of study results
      will lead to doubtful conclusions and prejudices. Results of such studies must be
      viewed with caution, and over-simplification as well as over-interpretation
      should be avoided.

PMID- 11248736
TI  - ACTH-receptor expression, regulation and role in adrenocortial tumor formation.
AB  - The regulation of the ACTH-receptor gene is unique in that it is up-regulated by
      its own ligand, ACTH. Ligand-induced up-regulation of ACTH-receptor expression
      may be an important adaptive process directed towards optimizing adrenal
      responsiveness to ACTH in the context of physiological stress and the maintenance
      of metabolic homeostasis in which the adrenals play a pivotal role. Whereas
      enhancement by ligand-induced up-regulation permits a more efficient and rapid
      glucocorticoid response, negative feedback regulation of glucocorticoids in the
      hypothalamus and pituitary inhibits ACTH secretion and allows a balanced adrenal
      response to stress. Since the cloning of the promoter region of the ACTH
      receptor, considerable progress in the understanding of the regulatory processes
      has been made. The effects of ACTH on ACTH-receptor expression is dependent on
      cAMP, probably mediated through AP-1. The profound effect of three SF-1-binding
      sites in the ACTH-receptor promoter was demonstrated by deletion experiments.
      Conversely, ACTH-receptor expression can be suppressed by adrenal-specific
      transcription factors,like DAX-1. Despite an extensive search, no activating ACTH
      receptor mutations have been found in adrenal tumors,excluding the ACTH receptor
      as a relevant oncogene in adrenal tumorigenesis. However, the ACTH receptor may
      act as a differentiation factor as suggested by LOH in adrenal carcinomas with an
      undifferentiated tumor type. In benign adrenal tumors, a strong correlation
      between ACTH-receptor expression and expression of P450 steroidogenic enzymes is
      evident. This close regulative relationship is lost in adrenal carcinoma,
      probably as a result of tumor dedifferentiation. Down-regulation of ACTH-receptor
      expression in normal and neoplastic tissue can be achieved by adrenostatic
      compounds such as aminoglutethimide and metyrapone.

PMID- 11248737
TI  - Mc3 and Mc4 receptors: complementary role in weight control.

PMID- 11248738
TI  - Protein kinase A in Carney complex: a new example of cAMP pathway alteration in
      endocrine tumors.

PMID- 11248739
TI  - Toward a consensus on reference values for thyroid volume in iodine-replete
      schoolchildren: results of a workshop on inter-observer and inter-equipment
      variation in sonographic measurement of thyroid volume.
AB  - OBJECTIVE: Interpretation of thyroid ultrasonography for assessing goiter
      prevalence requires valid reference criteria from iodine-sufficient populations.
      Reports have suggested the current reference criteria for thyroid volume (T(vol))
      of WHO/ICCIDD (International Council for the Control of Iodine Deficiency
      Disorders) may be too high. Our objective was to determine if inter-observer
      and/or inter-equipment variability contributes to the disagreement in sonographic
      T(vol) in children reported from iodine-sufficient areas. DESIGN: A 2-day
      workshop in which four experienced ultrasound examiners from around Europe
      measured T(vol) in 45 6--12-year-old Swiss schoolchildren using four different
      portable ultrasound machines. One of the participating examiners (observer A) had
      generated the T(vol) data in European children that are the basis for the
      WHO/ICCIDD reference criteria. METHODS: Sonographic T(vol) was measured in each
      child by all four examiners on all four machines. Six hundred and eighty-four
      examinations were completed, with examiners having no knowledge of one another's
      results. Inter-observer and inter-equipment variation was calculated. RESULTS:
      Mean inter-equipment variation in T(vol) was 15.2% (95% CI: 14.1, 16.3%). There
      were no significant differences in T(vol) between equipment (P=0.51). For all
      observers, the mean inter-observer variation in T(vol) was 25.6% (95% CI: 23.9,
      27.2%). At all ages and all body surface areas, there was a large systematic
      measurement bias (+30% volume) between the mean T(vol) of observer A and the mean
      Tvol of observers B, C and D. Reanalysis using data from observers B, C and D
      reduced the mean inter-observer variation in T(vol) to 13.3% (95% CI: 11.9,
      14.7%). A correction factor for the systematic difference of operator A for the
      P50 and P97 of T(vol) was estimated using analysis of covariance. When applied to
      the WHO/ICCIDD reference data, it sharply reduced the discrepancy between the
      WHO/ICCIDD criteria and those from other iodine-sufficient children around the
      world. CONCLUSIONS: Inter-equipment error contributes minimally to reported
      differences in sonographic T(vol). Even among experienced examiners, inter
      observer variation in sonographic T(vol) in children can be high, and probably
      contributes to the current disagreement on normative values in iodine-sufficient
      children. A systematic bias at least partially explains why the WHO/ICCIDD
      reference data differ from those reported from other iodine-sufficient children
      around the world. The findings argue strongly for the standardization of methods
      used for sonographic measurement of T(vol) in children.

PMID- 11248740
TI  - Thyroid morphology in lethal non-thyroidal illness: a post-mortem study.
AB  - OBJECTIVE: Non-thyroidal illness (NTI) is associated with alterations in thyroid
      hormone metabolism. Whether morphological changes of the thyroid gland accompany
      NTI is unknown. The aim of the present study was to describe thyroid morphology
      in patients with lethal non-thyroidal disease. DESIGN: In an autopsy study 267
      cases have been examined. METHODS: Clinical data were obtained from medical
      records. Subjects were patients with chronic disease (group A), intensive care
      patients (group B) or persons who had died suddenly without pre-existing
      illnesses (group C). Patients (n = 93) who did not fit into one of these
      categories and subjects with pre-existing thyroid disorders were excluded.
      Thyroid histology was assessed semi-quantitatively: grade I <25%, grade II 25-
      50% or grade III >75% occupation of the thyroid gland by follicles with a
      diameter <200 microm. RESULTS: Mean thyroid weight was 19.9 g in group A (n=75,
      age 19--96 (median 75) years, 48 males); 25.7 g in group B (n=64, age 24--93
      (median 69) years, 43 males); and 26.0 g in group C (n=35, age 31--89 (median 69)
      years, 22 males) (P<0.0005, A vs B/C). Grade I thyroid histology was present in 6
      out of 75 patients with chronic illness, in 3 out of 64 intensive care patients
      and in 33 out of 35 sudden-death subjects. Grade III thyroid histology occurred
      in 30 out of 75 chronically ill patients, in 17 out of 64 intensive care patients
      and in 0 out of 35 sudden-death subjects (P<0.0005, C vs A/B). CONCLUSIONS: NTI
      is associated with reduced thyroid follicular size that is accompanied by lower
      thyroid weight in chronically ill patients but not significantly in intensive
      care patients.

PMID- 11248741
TI  - Two familial giant pituitary adenomas associated with overweight: clinical,
      morphological and genetic features.
AB  - OBJECTIVE: Pituitary adenomas are usually sporadic, although rare familial cases
      have been described. Here we report two first degree female cousins with giant
      pituitary adenoma and overweight. Both presented with secondary amenorrhoea,
      occasional headache and weight gain. MATERIALS AND METHODS: In both patients
      clinical, morphological and genetic studies were performed. Both patients
      underwent surgery and post-operative medical therapy with somatostatin analogues
      and dopamine agonist, followed by a conventional radiotherapy course. RESULTS:
      Clinical examination at presentation revealed an acromegaloid habitus only in the
      second patient. Basal and dynamic hormonal evaluation showed high serum GH and
      serum IGF-I values, higher in the second than in the first patient, and a mild
      hyperprolactinaemia only in the first patient. On optical and electron
      microscopy, both tumours were oncocytic adenomas, immunopositive for GH in the
      first patient and GH/prolactin in the second. The genetic analysis for germ-line
      mutations of the multiple endocrine neoplasia type 1 gene was negative. Two years
      after radiotherapy a remarkable shrinkage of both tumours was observed, whereas
      the overweight worsened in both patients, accompanied by high plasma leptin
      values. CONCLUSION: To our knowledge, this is the first report of familial
      pituitary adenomas including one case of a clinically silent GH-secreting
      adenoma. In addition, it provides further evidence that familial pituitary
      tumours can occur as a multiple endocrine neoplasia type 1 unrelated disease.

PMID- 11248742
TI  - IGFs and IGF-binding proteins in short children with steroid-dependent nephrotic
      syndrome on chronic glucocorticoids: changes with 1 year exogenous GH.
AB  - OBJECTIVE: Children with steroid-dependent nephrotic syndrome (SDNS), despite
      being in remission on glucocorticoids, continue to have growth retardation and
      short stature. The mechanism is uncertain as both chronic glucocorticosteroids
      and the nephrotic syndrome may independently affect growth. We investigated the
      changes in the IGFs and IGF-binding proteins (IGFBPs) in a group of short SDNS
      children, and studied the changes prospectively with 1 year's treatment with GH.
      DESIGN AND METHODS: Total and 'free' IGF-I, IGFBP-3 and acid-labile subunit (ALS)
      were studied in eight SDNS boys (mean age=12.6 years; mean bone age=9.1 years) on
      long term oral prednisolone (mean dose 0.46 mg/kg per day) before, during, and
      after, 1 year's treatment with GH (mean dose 0.32 mg/kg per week). Pretreatment
      comparisons were made with two control groups, one matched for bone age (CBA;
      mean bone age=9.2 years), and another for chronological age (CCA; mean
      chronological age=13 years). Subsequently, three monthly measurements of serum
      and urine IGFBPs were carried out in the GH-treated SDNS patients using Western
      ligand blot and Western immunoblot. RESULTS: Pre-treatment serum total IGF-I
      levels and the IGF-I/IGFBP-3 ratio were elevated significantly in SDNS compared
      with CBA, and were similar to CCA. Serum free IGF-I levels were elevated
      significantly compared with both control groups, but serum IGFBP-3 did not differ
      significantly. Urinary IGFBP-2, IGFBP-3 and ALS were detectable in the SDNS
      children only. With GH treatment, IGF-I and IGFBP-3, but not IGF-II, increased
      significantly compared with pre-treatment values, and returned to baseline after
      cessation of GH treatment. Urinary IGFBPs did not change significantly with GH
      treatment. CONCLUSIONS: There is persistent urinary loss of IGFBP-2, IGFBP-3 and
      ALS in children with SDNS in remission with growth retardation. However, the
      significant elevation in serum IGF-I suggests that glucocorticoid-induced
      resistance to IGF is the main factor responsible for the persistent growth
      retardation in these children. Exogenous GH was able to overcome this resistance
      by further increasing serum IGF-I.

PMID- 11248743
TI  - Diagnostic interest of acid-labile subunit measurement in relationship to other
      components of the IGF system in pediatric patients with growth or eating
      disorders.
AB  - OBJECTIVE: To analyze the possible utility of measuring acid-labile subunit (ALS)
      in some types of pathologies in which the IGF system is altered and to compare it
      with the clinical implications of measurements of other components of this axis.
      DESIGN AND METHODS: We studied serum ALS concentrations in 20 children with
      normal variants of short stature (NVSS) at diagnosis and 24 with growth hormone
      deficiency (GHD), 18 obese patients and 18 girls with anorexia nervosa at
      diagnosis and during a follow-up period. RESULTS: In patients with GHD and
      anorexia nervosa, mean ALS concentrations were significantly reduced, but there
      was a high percentage of overlap with control values. At diagnosis, ALS
      concentrations were normal in obese patients and children with NVSS. During
      follow-up, these values normalized in children with GHD who were treated with GH,
      tended to normalize in those with anorexia nervosa who showed weight gain, and
      did not change in obese children upon weight loss. However, ALS measurement was
      less accurate than that of IGF-I or IGF binding protein (IGFBP)-3 in diagnosis of
      GHD. The correlations found between ALS and some IGF system components at
      diagnosis either decreased or were non-significant during follow-up of these
      clinical conditions. CONCLUSION: ALS adds little information to that obtained
      with IGF-I and IGFBP-3 determinations.

PMID- 11248744
TI  - Effects of short-term administration of low-dose rhGH on IGF-I levels in obesity
      and Cushing's syndrome: indirect evaluation of sensitivity to GH.
AB  - OBJECTIVE: To verify the hypothesis of an increased sensitivity to GH in obesity
      (OB) and Cushing's syndrome (CS). DESIGN: We studied the effects of short-term
      administration of low-dose rhGH on circulating IGF-I levels in patients with
      simple OB or CS and in normal subjects (NS). METHODS: Nineteen women with
      abdominal OB aged (mean +/- s.e.m.) 38.2+/-3.1 years, body mass index 40.7+/-2.5
      kg/m(2), waist to hip ratio 0.86+/-0.02, ten with CS (50.4+/-4.2 years, 29.7 +/-
      3.3 kg/m(2)) and 11 NS (35.0+/-3.6 years, 20.5+/-0.5 kg/m(2)) underwent s.c.
      administration of 5 microg/kg per day rhGH at 2200 h for four days. Serum IGF-I,
      IGF-binding protein-3 (IGFBP-3), GH-binding protein (GHBP), insulin and glucose
      levels were determined at baseline and 12 h after the first and the last rhGH
      administration. RESULTS: Basal IGF-I levels in NS (239.3+/-22.9 microg/l) were
      similar to those in OB (181.5+/-13.7 microg/l) and CS (229.0+/-29.1 microg/l).
      Basal IGFBP-3, GHBP and glucose levels in NS, OB and CS were similar while
      insulin levels in NS were lower (P<0.01) than those in OB and CS. In NS, the low
      rhGH dose induced a sustained rise of IGF-I levels (279.0+/-19.5 microg/l,
      P<0.001), a non-significant IGFBP-3 increase and no change in GHBP, insulin and
      glucose levels. In OB and CS, the IGF-I response to rhGH showed progressive
      increase (246.2+/-17.2 and 311.0+/-30.4 microg/l respectively, P<0.01 vs
      baseline). Adjusting by ANCOVA for basal values, rhGH-induced IGF-I levels in CS
      (299.4 microg/l) were higher than in OB (279.1 microg/l, P<0.01), which, in turn,
      were higher (P<0.05) than in NS (257.7 microg/l). In OB, but not in CS, IGFBP-3
      and insulin levels showed slight but significant (P<0.05) increases during rhGH
      treatment, which did not modify glucose levels in any group; thus, in the OB
      patient group a significant fall in glucose/insulin ratio was observed.
      CONCLUSIONS: Short-term treatment with low-dose rhGH has enhanced stimulatory
      effect on IGF-I levels in OB and, particularly, in hypercortisolemic patients.
      These findings support the hypothesis that hyperinsulinism and hypercortisolism
      enhance the sensitivity to GH in humans.

PMID- 11248745
TI  - Calcium sensing receptor gene polymorphism, circulating calcium concentrations
      and bone mineral density in healthy adolescent girls.
AB  - OBJECTIVE: Bone mineral density (BMD) in adolescence is under strong genetic
      control. The calcium sensing receptor (CASR) is involved in the regulation of
      calcium homeostasis and bone resorption. The A986S polymorphism of the CASR has
      recently been associated with serum calcium levels, in one hitherto unconfirmed
      report. We investigated whether this polymorphism was related to BMD, circulating
      calcium and parathyroid hormone (PTH) concentrations in girls. DESIGN: BMD,
      plasma calcium and serum PTH were measured in adolescent girls and compared with
      regard to CASR genotype. METHODS: In 97 healthy Caucasian girls (mean age 16.9+/
      1.2 years (mean+/-s.d.)), the A and S alleles were determined using PCR with a
      mismatched primer and the restriction enzyme BsaHI. BMD (g/cm) of the total body,
      humerus, femoral neck and lumbar spine was measured using dual energy X-ray
      absorptiometry. RESULTS: The genotype frequencies were 71% AA, 26% AS and 3% SS.
      The genotypes were divided into presence (29%) or absence of S allele (71%).
      Subjects with the S allele had higher levels of plasma calcium, corrected for
      albumin (2.17+/-0.06>2.14+/-0.06; P < 0.05, using independent samples t-test),
      lower BMD at the lumbar spine (P=0.02) and total body (P=0.04), and were
      significantly less physically active (2.9+/-2.6 vs 4.3+/-2.6 h/week; P=0.01) than
      the subjects lacking the S allele. PTH levels were not significantly different
      between the two allelic groups. A multiple regression analysis, including age,
      height, weight and physical activity, revealed that the CASR allelic variants
      were not independent predictors of BMD at any site measured (beta=-0.03-0.09;
      P>0.05). Physical activity was an independent predictor of BMD, was significantly
      different between the CASR genotypes, and could therefore have a role in
      explaining the difference in BMD between the CASR genotypes. CONCLUSIONS: The
      CASR alleles are related to BMD, but it cannot be definitely concluded whether
      the CASR polymorphism has a direct influence on BMD, or whether the differences
      in BMD were mediated via an influence of the amount of physical activity.

PMID- 11248746
TI  - Skeletal responsiveness to parathyroid hormone in pseudohypoparathyroidism.
AB  - BACKGROUND: Although there have been some case reports suggesting that bone in
      patients with pseudohypoparathyroidism (PHP) might respond to parathyroid hormone
      (PTH), no information is available as to whether serum PTH concentration is
      related to bone metabolic markers or to bone mineral density (BMD) in PHP.
      OBJECTIVE: To address these relationships, by comparing intact serum PTH, bone
      metabolic markers and BMD in patients with PHP with those in patients with
      idiopathic hypoparathyroidism (IHP) and postoperative hypoparathyroidism (OHP).
      METHODS: Intact serum PTH, bone metabolic markers (osteocalcin, tartrate
      resistant acid phosphatase, pyridinoline, deoxypyridinoline) and BMD by dual
      energy X-ray absorptiometry or single-photon absorptiometry were measured in
      patients with PHP Ia (n=2) and PHP Ib (n=8). The results were compared with those
      in patients with IHP (n=5) and OHP (n=14). RESULTS: All bone metabolic markers
      measured were present in significantly greater amounts in patients with PHP Ib
      than in those with IHP+OHP. The Z score (standard deviation of average BMD at
      each age) of the BMD of femoral neck was significantly lower in patients with PHP
      Ib than in those with IHP+OHP. The Z scores of BMD of lumbar spine and radius
      were also lower in patients with PHP Ib than in those with IHP+OHP, but the
      difference was not significant. Moreover, the intact serum PTH concentrations
      were significantly and positively related to bone metabolic marker levels in all
      patients, and the intact serum PTH concentrations were significantly and
      negatively related to BMD of lumbar spine in PHP patients. CONCLUSIONS: These
      results suggest that PTH stimulates bone turnover in PHP Ib patients, resulting
      in a relatively lower BMD in PHP Ib patients than in IHP+OHP patients. The
      present study indicates that bones of most cases of PHP could respond to PTH.

PMID- 11248747
TI  - Abundant expression of platelet-derived growth factor in spiral arteries in
      decidua associated with pregnancy-induced hypertension and its relevance to
      atherosis.
AB  - OBJECTIVE: To elucidate the role of platelet-derived growth factor (PDGF) in the
      pathophysiology of pregnancy-induced hypertension (PIH) in which the spiral
      arteries of the decidua demonstrate the atherosclerotic change. DESIGN AND
      METHODS: We determined serum levels of PDGF and PDGF expression in the decidua as
      well as serum levels of 17 beta-estradiol (E2) and progesterone (P4) both in
      normotensive cases and in PIH cases. Furthermore, we investigated whether sex
      steroid hormones could interact with PDGF in cultured vascular smooth muscle
      cells (SMC) by immunohistochemical staining for proliferating cell nuclear
      antigen. RESULTS: Serum PDGF levels were higher (P<0.01) but serum E2 levels were
      lower (P<0.01) in PIH cases compared with normotensive cases. There was no
      statistically significant difference between serum P4 levels in PIH cases and
      those in normotensive cases. Immunohistochemical staining for PDGF in SMC of
      spiral arteries was more prominent in PIH cases than in normotensive cases. The
      proliferative potential of cultured SMC was stimulated by PDGF, but inhibited by
      concomitant treatment with PDGF and E2. CONCLUSIONS: PDGF is suggested to play an
      important role in the pathophysiology of PIH through its stimulatory effect on
      vascular SMC proliferation which may elicit the atherosclerotic change in the
      spiral arteries of the placenta.

PMID- 11248748
TI  - A Pro12Ala polymorphism in the human peroxisome proliferator-activated receptor
      gamma 2 is associated with combined hyperlipidaemia in obesity.
AB  - OBJECTIVE: Peroxisome proliferator-activated receptor-gamma 2 (PPAR gamma 2) is
      an important regulator of adipose tissue metabolism and insulin sensitivity. The
      aim of this investigation was to determine whether a PPAR gamma 2 Pro12Ala
      polymorphism was associated with cardiovascular risk factors (obesity, blood
      pressure, diabetes and blood lipids) in Western Australian Caucasians (n=663).
      DESIGN: Subjects were selected from two population studies (the Carotid
      Ultrasound Disease Assessment Study (CUDAS) and Busselton Population Health
      Survey) on the basis of body mass index (BMI). 292 obese (BMI > or =30 kg/m) and
      371 lean (BMI <25 kg /m) subjects were studied. METHODS: Blood pressure and
      anthropometric measurements were collected from all participants, as well as a
      fasting venous blood sample. Biochemical measurements (high-density lipoprotein
      (HDL)- and low-density lipoprotein-cholesterol, triglycerides) and PPAR gamma 2
      Pro12Ala genotype were also determined. RESULTS: Obese Pro/Ala and Ala/Ala
      subjects had lower levels of HDL-cholesterol (P=0.032) and a trend towards higher
      levels of triglycerides (P=0.055) compared with obese Pro/Pro subjects. In the
      obese group, the Ala allele was significantly associated with the presence of
      combined hyperlipidaemia (odds ratio = 2.33, P=0.042). There was no significant
      difference in the frequency of the polymorphism between lean and obese groups
      (P=0.069). No association was observed between Pro12Ala genotype and obesity,
      blood pressure or diabetes in either group. CONCLUSIONS: Obese carriers of the
      Pro12Ala polymorphism have a greater risk of developing combined hyperlipidaemia,
      possibly due to impaired activation of PPAR gamma target genes. The Pro12Ala
      polymorphism is not directly associated with obesity, hypertension or diabetes in
      this population.

PMID- 11248749
TI  - Circulating IGF binding protein-1 is inversely associated with leptin in non
      obese men and obese postmenopausal women.
AB  - OBJECTIVE: Hyperleptinaemia and hyperinsulinaemia interrelate to insulin-like
      growth factor binding protein 1 (IGFBP-1), and disturbances in the growth hormone
      IGF-I axis are linked to obesity and cardiovascular diseases. However, whether
      the association between leptin and the GH-IGF-I axis is altered with increasing
      obesity is not known. We therefore examined the relationship between leptin, IGF
      I, IGFBP-1, insulin and proinsulin in men and women with or without obesity in a
      population study. DESIGN AND SUBJECTS: Healthy subjects (n=158; 85 men and 73 pre
      and postmenopausal women) from the Northern Sweden MONICA (Monitoring of Trends
      and Determinants in Cardiovascular Disease) population were studied with a cross
      sectional design. METHODS: Anthropometric measurements (body mass index (BMI) and
      waist circumference) and oral glucose tolerance tests were performed.
      Radioimmunoassays were used for the analyses of leptin, IGF-I and IGFBP-1, and
      ELISAs for specific insulin and proinsulin. RESULTS: Leptin inversely correlated
      to IGFBP-1 in non-obese men (P<0.05) and obese postmenopausal women (P<0.05). In
      contrast, leptin did not correlate to IGF-I. IGFBP-1 was also significantly
      associated with proinsulin in non-obese men (P<0.01) and non-obese premenopausal
      women (P<0.05). The association between leptin and IGFBP-1 was lost after
      adjustment for insulin. In multivariate analyses taking measures of adiposity
      into account, low proinsulin, and IGF-I in combination with old age, but not
      leptin, predicted high IGFBP-1 levels. CONCLUSIONS: Leptin was inversely
      associated with IGFBP-1 in non-obese men and obese postmenopausal women, and
      proinsulin was inversely associated with IGFBP-1 in non-obese men and
      premenopausal women. However, these associations were lost with increasing
      central obesity in men and premenopausal women and after control for insulin.
      Therefore, this study suggests (i) that leptin is of minor importance for
      regulation of IGFBP-1 levels and (ii) that the insulin resistance syndrome is
      characterised by an altered relationship between leptin, IGFBP-1 and insulin.

PMID- 11248750
TI  - Identification of a deletion variant in the gene encoding the human alpha(2A)
      adrenergic receptor.
AB  - OBJECTIVE: The alpha(2)-adrenergic receptors are involved in the effects of
      catecholamines on energy metabolism. Of three known subtypes with differential
      expression, alpha(2A)-adrenergic receptors are also localized in adipose tissue
      where they counteract the lipolytic activity of beta-adrenergic receptors. This
      study was undertaken to assess whether variants in the alpha(2A)-adrenergic
      receptor gene are associated with body weight. DESIGN AND METHODS: Single strand
      conformation polymorphism (SSCP) screening and subsequent sequencing were applied
      to determine genetic variants in DNA samples from individuals with obesity, those
      of normal weight and those underweight. RESULTS: Analysis of the coding region
      resulted in the identification of an 18 bp deletion, with no other mutation
      found. Of 429 genotyped subjects, 7 carried the deletion, with no significant
      differences between lean and obese subjects. A previously identified polymorphism
      in the promoter of the alpha(2A)-adrenergic receptor gene also did not show an
      association with any of the tested body weight categories. CONCLUSION: Our data
      suggest that variants in the alpha(2A)-adrenergic receptor gene are unlikely to
      contribute to the predisposition for the lean or obese state.

PMID- 11248752
TI  - Effects of nitric oxide on steroidogenesis in porcine granulosa cells during
      different stages of follicular development.
AB  - BACKGROUND: We have previously demonstrated that nitric oxide (NO) inhibits
      steroidogenesis via a cGMP-independent process, by inhibiting P450 aromatase
      activity in porcine granulosa cells (PGCs) derived from medium-sized (3--5 mm)
      ovarian follicles (M-PGC). OBJECTIVE: To determine whether the NO/NO synthase
      (NOS) system exerts any significant effects on steroidogenesis in PGCs derived
      from small follicles (<3 mm) (S-PGC) in comparison with those derived from medium
      follicles. DESIGN AND METHODS: PGCs, namely S-PGC and M-PGC, were incubated with
      the NO donor, NOC18, and a competitive blocker of NOS, N(3)-monomethyl-l-arginine
      (LNMMA), either alone or in the presence of FSH (200 ng/ml) or hCG (5 IU/ml).
      RESULTS: NOC18 significantly (P<0.01--0.001) suppressed basal (unstimulated) and
      gonadotropin-stimulated estradiol (E2) release from both S-PGC and M-PGC in a 2-h
      culture. NOC18 significantly (P<0.01--0.001) decreased basal and gonadotropin
      stimulated progesterone release from S-PGC, but not from M-PGC. In addition,
      NOC18 significantly (P<0.05--0.001) inhibited aromatase activity in S-PGC. LNMMA
      had a significantly (P<0.01--0.001) stimulatory effect on the basal release of E2
      and progesterone from M-PGC; however, it had no significant effect on basal
      steroidogenesis in S-PGC in a 24-h culture. In the presence of gonadotropin,
      LNMMA significantly (P<0.01--0.001) stimulated the release of E2 and progesterone
      from both S- and M-PGC, and this stimulatory effect was weaker in S-PGC than in M
      PGC. These results demonstrate that NO inhibits E2 secretion by directly
      inhibiting the aromatase activity in S-PGC, as in M-PGC. It has been shown that
      the NO system suppresses the differentiation of S-PGC; however, the extent of
      suppression decreased with the progression of follicular growth. In addition, the
      activity of NOS in S-PGC was weaker than that in M-PGC. CONCLUSION: We strongly
      suggest that the NO/NOS system in PGC regulates steroidogenesis differently
      during different phase of follicular development.

PMID- 11248753
TI  - Pregnancy in a patient with type 1 diabetes mellitus and prior ischaemic heart
      disease.

PMID- 11248751
TI  - Na(+)/I(-) symporter and Pendred syndrome gene and protein expressions in human
      extra-thyroidal tissues.
AB  - OBJECTIVE: The expression of two recently identified iodide transporters, namely
      the sodium/iodide symporter (NIS) and pendrin, the product of the gene
      responsible for the Pendred syndrome (PDS), was studied in a series of various
      extra-thyroidal human tissues, and especially in those known to concentrate
      iodide. METHODS: To this end, we used real-time kinetic quantitative PCR to
      detect NIS and PDS transcripts and immunohistochemistry for the analysis of their
      protein products. RESULTS: NIS gene and protein expression was detected in most
      tissues known to concentrate iodine, and particularly in salivary glands and
      stomach. In contrast, PDS gene expression was restricted to a few tissues, such
      as kidney and Sertoli cells. Interestingly, in kidney, pendrin immunostaining was
      detected at the apical pole of epithelial cells of the thick ascending limb of
      the Henle's loop and of the distal convoluted tubule. CONCLUSION: This study
      provides new insights on the localization and expression of two genes involved in
      iodide transport and emphasizes the interest of combining real-time quantitative
      PCR and immunohistochemistry for the comparison of gene and protein expression in
      tissues.

PMID- 11248755
TI  - The importance of 24-h blood pressure control.
AB  - The primary goal of antihypertensive therapy is to restore blood pressure to
      normal levels and to prevent the complications associated with hypertension. In
      order to maximize these goals by improving patient compliance, clinical
      researchers have focused on developing antihypertensive agents that can be given
      once daily. These agents provide many advantages over multiple-dose daily
      therapies, but it should not be assumed that they are all equivalent in providing
      adequate blood pressure control over the full 24-h dosing interval. Ambulatory
      blood pressure monitoring has uncovered important differences in commonly used
      once-daily therapies and has provided additional insights into the cardiovascular
      risks associated with high blood pressure loads and blood pressure variability.
      In addition to ambulatory blood pressure monitoring data, the calculated
      trough:peak ratio provides useful information on an agent's ability to provide
      smooth and consistent blood pressure control. Using such assessments, it has been
      found that agents with a trough:peak ratio > or = 0.50 are better able to control
      blood pressure over the full 24h while maintaining natural circadian patterns.
      Ambulatory blood pressure monitoring studies assessing a recently introduced
      class of antihypertensive drugs, the angiotensin receptor blockers, have
      demonstrated 24-h efficacy with once-daily dosing, particularly with the newer
      agents.

PMID- 11248756
TI  - Prevalence of blood pressure cuff sizes in a referral practice of 430 consecutive
      adult hypertensives.
AB  - Accurate measurement of blood pressure is dependent on a number of factors
      including use of the appropriate sized cuff. Overestimation of blood pressure by
      using an inappropriately small cuff has been well documented. The prevalence of
      the use of the standard adult and large adult cuffs in hypertensive patients is
      less well defined in the literature. Worldwide, the increasing prevalence of
      obesity and its associated conditions such as hypertension accentuates the
      importance of the recognition of the relationship of appropriate sized cuff and
      accurate blood pressure measurement. This is the largest study to define the
      prevalence of blood pressure cuff sizes in a hypertensive population. Vendors of
      blood pressure measurement devices should be aware of the changing demographics
      and the need for the large adult arm cuff to be routinely available.

PMID- 11248754
TI  - Blood pressure monitoring during pregnancy.
AB  - Hypertensive disease in pregnancy represents a significant health problem in the
      world, and ranks second only to thromboembolism as a cause of maternal mortality
      in the USA. In addition, hypertension is associated with both perinatal morbidity
      and mortality secondary to direct effects on the fetus as well as the iatrogenic
      preterm deliveries performed for maternal indications. Conventional (office,
      mercury column or aneroid manometry) blood pressure measurement is the most
      common screening test performed during prenatal visits. During the past several
      years, investigators have focused on the use of 24-h ambulatory and automated
      self (or home) blood pressure monitoring during pregnancy. This review article
      summarizes the current literature on both ambulatory and home blood pressure
      monitoring in pregnancy and how they relate to various clinical aspects of
      hypertension in pregnancy.

PMID- 11248757
TI  - Comparison of the actigraph versus patients' diary information in defining
      circadian time periods for analyzing ambulatory blood pressure monitoring data.
AB  - BACKGROUND: Assessment of 24-h changes in blood pressure is one of the unique
      features that ambulatory blood pressure monitoring (ABPM) can provide. Most
      studies agree that sleep/wake periods should be based on patients' actual sleep
      and wake times. Actual wake and sleep time determinations are often based on
      patients' diary information. Several publications indicate that actigraphy is, at
      least, as accurate as activity diary in determining sleep/wake periods.
      OBJECTIVES: To compare subjects' compliance with actigraphy and diary keeping and
      to compare actigraphy and diary data in determination of sleep and wake times,
      mean blood pressures, classification of hypertension, and assessment of nocturnal
      dipping status. METHODS: We evaluated ABPM studies of 62 subjects. Blood pressure
      data were obtained using Spacelabs monitors for 24h. Sleep and wake times were
      determined by both the actigraph and patients' activity diary. RESULTS: In the 62
      studies, 56 subjects had successful actigraphy (90%), 44 had activity diary
      completion (71%), and 38 subjects had both (61%). There was no statistically
      significant difference between the mean wake and sleep onset using the two
      methods, but up to 3 hours' difference in wake or sleep onset was noted in some
      studies. Although the two methods did not significantly affect the calculated
      systolic blood pressure (SBP) or diastolic blood pressure (DBP) loads in either
      awake or sleep periods, approximately 55% of the subjects' dipping status was
      changed when diary information on sleep time was used compared to actigraph.
      CONCLUSIONS: Our data indicate that in children and young adults, compliance with
      the actigraph was superior to diary completion and use of the actigraphy method
      rather than diary information changed the interpretation of some ABPM data. Our
      study suggested that actigraphy is superior to diary keeping in providing the
      information needed for appropriate interpretation of some ABPM data.

PMID- 11248758
TI  - Polymorphism insertion/deletion of the ACE gene and ambulatory blood pressure
      circadian variability in essential hypertension.
AB  - OBJECTIVE: The objective of the present study was to analyze the influence of the
      insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme on
      ambulatory blood pressure values and circadian variability in untreated patients
      with hypertension. MATERIAL AND METHODS: Ninety-nine essential hypertensive
      patients, less than 50 years old (mean age 39.5+/-7.0 years), previously
      untreated with antihypertensive drugs were included. Twenty-four hour ambulatory
      blood pressure monitoring (ABPM) was performed with a Spacelabs (90202 and 90207)
      monitor, during a regular working day in unrestricted ambulatory conditions. The
      I/D polymorphism of the ACE was determined by PCR. RESULTS: The distributions of
      genotypes were in Hardy-Weinberg equilibrium: I=17 (17%), ID=41 (41.5%), DD=41
      (41.5%). No significant differences were present among the groups in terms of
      age, sex, and biochemical and lipid profiles. The average of 24-h ambulatory
      blood pressure was slightly higher in patients with the DD genotype as compared
      with patients with the II and ID genotypes. This was the result of higher
      nighttime blood pressure values, because no differences in blood pressure were
      observed during daytime. The systolic blood pressure (SBP) day:night ratio, as an
      estimate of circadian variability, was significantly lower in subjects homozygous
      for the D allele than it was in patients carrying the I allele (1.13+/-0.09 vs.
      1.17+/-0.08, P=0.014). The subjects in the lowest tertile of the SBP day:night
      ratio, exhibited a higher frequency of the D allele when compared with those in
      the middle tertile (0.74 vs. 0.59, P<0.05) or with those in the highest tertile
      (0.74 vs. 0.54, P<0.01). By using two-way ANOVA with repeated measures,
      significant differences in SBP variation over time were observed when comparing
      homozygous for the D allele with subjects carrying the I allele (F=2.11,
      P=0.002). CONCLUSIONS: Among the genotypes of the I/D polymorphism, subjects
      carrying DD genotype showed a blunted decline of the physiological nocturnal fall
      of blood pressure that was significant for SBP.

PMID- 11248759
TI  - Effect of altering vasoactivity on the measurement of finger blood pressure.
AB  - BACKGROUND: Finapres monitors and oscillometric sphygmomanometers are widely used
      in blood pressure measurements on the fingers. However, the reliability of finger
      blood pressure measurement devices still remains a matter of debate. DESIGN: The
      volume clamp and modified oscillometric methods for non-invasive beat-to-beat
      finger mean arterial pressure monitoring are compared during intensive
      spontaneous changes in vascular tone. The degree of vasoconstriction is
      established by recording the thumb pulp skin blood flow with a laser Doppler
      instrument. The oscillometric mean arterial pressure (MAPo) and the Finapres mean
      arterial pressure (MAPf) are simultaneously recorded from adjacent fingers in
      eight healthy volunteers in a sitting position at room temperature 22-23 degrees
      C. RESULTS: The changes in blood pressure were similarly tracked by the two blood
      pressure monitors, except the episodes with peripheral vasoconstriction. The
      difference (MAPo-MAPf) for all simultaneously recorded mean blood pressure values
      in episodes without vasoconstriction was (mean+/-SD) 0.7+/-1.8mmHg (P=0.33) and
      in episodes with vasoconstriction 10.6+/-5.6mmHg (P<0.01). A disagreement between
      the devices during vasoconstriction is assumed to be caused mainly by the
      tendency of the oscillometric method to overestimate the finger mean blood
      pressure, and by the tendency of the volume clamp method (Finapres) to
      underestimate the finger mean blood pressure in condition of peripheral
      vasoconstriction. CONCLUSION: For both types of finger monitors (oscillometric
      blood pressure devices as well as Finapres or Portapres) it is recommended that
      intensive vasoconstriction in the subject be avoided during measurements. The
      presence of acute vasoconstrictions can be determined by simultaneous recording
      of finger skin blood flow.

PMID- 11248760
TI  - Reproducibility of ambulatory blood pressure measurements in essential
      hypertension.
AB  - BACKGROUND: Data on the reproducibility of serial measurements of ambulatory
      blood pressure in hypertensive patients are lacking. The purpose of this study
      was to examine (1) the reproducibility of four consecutive ambulatory blood
      pressure measurements, and (2) the reproducibility of nocturnal falls in blood
      pressure in hypertensive patients. METHODS: Twenty patients with mild to moderate
      essential hypertension underwent four separate ambulatory blood pressure
      monitorings, on the same day of the week, at 30-day intervals. Antihypertensive
      therapy was discontinued for 2 weeks before each recording. Comparing the mean
      values of blood pressure over 24h, as well as diurnal, nocturnal and hourly
      periods, among the four recordings determined the reproducibility of blood
      pressure measurements. A day/night difference in mean systolic and in mean
      diastolic blood pressure defined the nocturnal fall in blood pressure. RESULTS:
      No significant differences were observed in either hourly, 24-h, diurnal or
      nocturnal systolic blood pressure, diastolic blood pressure and heart rate, or in
      the nocturnal fall in systolic and diastolic blood pressure among the four
      recordings. CONCLUSIONS: Hourly systolic blood pressure, diastolic blood
      pressure, heart rate, and nocturnal fall in blood pressure were reproducible in
      four ambulatory blood pressure monitorings recorded over 4 months. These findings
      suggest that ambulatory blood pressure monitoring is a reliable tool to monitor
      blood pressure changes.

PMID- 11248761
TI  - Comparative effects of amlodipine and nifedipine GITS during treatment and after
      missing two doses.
AB  - OBJECTIVE: To compare the antihypertensive efficacy of amlodipine and nifedipine
      gastrointestinal therapeutic system (GITS) measured by office and ambulatory
      blood pressure monitoring (ABPM) during treatment and, after patients have missed
      two doses. METHOD: After a single blind run-in 4-week placebo period, 58 patients
      were randomly allocated to amlodipine (5mg/daily, n=30) or nifedipine GITS
      (30mg/daily; n=28) in a double-blind, double dummy fashion. Patients received
      active medication for 4 weeks. Then, to simulate failure of compliance, patients
      received two single blinded doses of placebo. Ambulatory blood pressure
      monitoring was carried out at the end of run-in placebo phase, the first day, the
      last day of active treatment and up to 72h after the last active dose. RESULTS:
      Diastolic blood pressure was controlled in 61.9% patients on amlodipine and 52.9%
      on nifedipine GITS. Reductions in blood pressure were similar in both groups.
      ABPM showed significant reduction in blood pressure from the first day in the
      nifedipine GITS group, while amlodipine group had marginal effect. Peak reduction
      in systolic/diastolic blood pressure was 26/15mmHg at 5-6h after ingestion of
      amlodipine tablets. The trough reduction was 22/13mmHg; with a trough-to-peak
      ratio of 84.61% for systolic and 86.67% for diastolic blood pressure. Peak
      reduction in systolic/diastolic blood pressure with nifedipine GITS was 19/15mmHg
      and the trough reduction was 21/17mmHg, giving a trough-to-peak ratio of 100% for
      both systolic and diastolic blood pressure. When patients received placebo after
      4 weeks of active treatment, simulating a compliance failure, amlodipine
      maintained reduction in systolic and diastolic blood pressure for at least up to
      72h after the last active dose, maintaining 57.71% of the effect for systolic
      blood pressure and 60.00% for diastolic blood pressure. In contrast, nifedipine
      GITS effect was rapidly lost during this study phase, with a reduction in
      systolic and diastolic blood pressure of only 14-16%, 72h after the last active
      dose. CONCLUSION: This study showed that amlodipine and nifedipine GITS reduce
      blood pressure to about the same extent during chronic treatment. In the case of
      compliance failure, such as missing one or two doses, amlodipine maintained
      significant and important antihypertensive effect with the trough-to-peak ratio
      still over 50% 72h after the last active dose. On the other hand, the coverage of
      nifedipine GITS was limited to about 36h after the last active dose.

PMID- 11248762
TI  - Electrical modulation of cardiac contractility in heart failure: the impulse
      dynamics signal. Editor's overview.

PMID- 11248763
TI  - Heart failure therapy at the turn of the century.
AB  - Major changes in the treatment of heart failure have occurred in the last fifty
      years that have had a dramatic effect on its morbidity and mortality. Over two
      hundred years have passed since the demonstration of the benefit of digitalis in
      heart failure to the development of potent loop diuretics. The observation that
      vasodilators could improve both cardiac function and mortality led to the
      investigation of the Angiotensin Converting Enzyme Inhibitors (ACEI). Although
      these agents had significant vasodilator properties, their major benefit appears
      to be related to their ability to effect remodeling of the failing left
      ventricle. The most recent randomized clinical trials demonstrate that Beta
      Adrenergic Blocking agents can provide an incremental effect on both mortality
      and morbidity when added to therapy with ACEI. Although these agents have
      improved the outlook for the heart failure patient, they have had very little
      effect on the improvement of left ventricular function. Future research must be
      directed at methods to deal with this issue by either changing the contractile
      properties of the cardiomyocyte by pharmacologic or electrical therapy or by
      transplanting functional cells that can increase the number of functioning
      contractile units.

PMID- 11248764
TI  - Congestive heart failure treatment: the pacing approach.
AB  - Early reports of physiologic pacing for congestive heart failure (CHF) yielded
      conflicting results, and little enthusiasm was generated for pacing as a mode of
      therapy for CHF. Small, uncontrolled studies, which had little or no follow-up
      demonstrated that pacing from the left ventricle could synchronize contraction of
      the ventricles and improve overall ventricular performance. These encouraging
      reports led to a number of larger, multicenter trials, which have been recently
      reported. These trials have consistently shown improvements in such objective
      measurements as peak exercise oxygen consumption, ejection fraction, heart rate
      variability, 6-minute walk test distance and anaerobic threshold, as well as
      subjective improvements such as quality of life assessment. A number of large,
      multicenter double-blinded trials are ongoing which will seek to further assess
      the benefits of biventricular or multisite pacing. Among the important issues,
      which will be addressed by ongoing trials, are the possibility of pacing induced
      arrhythmias, the benefit of adding defibrillator capability to these pacing
      systems, and the development of novel delivery systems, which will make
      implantation of these systems more accessible to clinicians. Studies to date have
      largely excluded patients with traditional indications for pacing, and have been
      confined chiefly to patients with PR interval prolongation, and left bundle
      branch block with a QRS duration greater than 120 milliseconds, with New York
      Heart Association class II or III CHF. Whether this therapy will offer benefit to
      other patients who do not meet these criteria is also unknown at present. Another
      novel mode of pacing therapy, which may be clinically appropriate for a broader
      range of CHF patients, is contractility modulation, which involves subthreshold
      pacing to increase intracellular calcium and enhance inotropy. Early data
      suggests that the benefits of these two forms of pacing therapy may be additive.

PMID- 11248765
TI  - Electric currents applied during the refractory period can modulate cardiac
      contractility in vitro and in vivo.

PMID- 11248766
TI  - Global improvement in left ventricular performance observed with cardiac
      contractility modulation is the result of changes in regional contractility.

PMID- 11248767
TI  - Cardiac contractility modulation with the impulse dynamics signal: studies in
      dogs with chronic heart failure.
AB  - The intravenous use of positive inotropic agents, such as sympathomimetics and
      phosphodiesterase inhibitors, in heart failure is limited by pro-arrhythmic and
      positive chronotropic effects. Chronic use of these agents, while eliciting an
      improvement in the quality of life of patients with advanced heart failure, has
      been abandoned because of marked increase in mortality when compared to placebo.
      Nevertheless, patients with advanced heart failure can benefit from long-term
      positive inotropic support if the therapy can be delivered 'on demand' and in a
      manner that is both safe and effective. In this review, we will examine the use
      of a novel, non-stimulatory electrical signal that can acutely modulate left
      ventricular (LV) contractility in dogs with chronic heart failure in such a way
      as to elicit a positive inotropic support. Cardiac contractility modulation (CCM)
      with the Impulse Dynamic(trade mark) signal was examined in dogs with chronic
      heart failure produced by intracoronary microembolizations. Delivery of the CCM
      signal from a lead placed in the great coronary vein for periods up to 10 minutes
      resulted in significant improvements in cardiac output, LV peak+dP/dt, LV
      fractional area of shortening and LV ejection fraction measured angiographically.
      Discontinuation of the signal resulted in a return of all functional parameters
      to baseline values. In cardiomyocytes isolated from dogs with chronic heart
      failure, application of the CCM signal resulted in improved shortening, rate of
      change of shortening and rate of change of relengthening suggesting that CCM
      application is associated with intrinsic improvement of cardiomyocyte function.
      The improvement in isolated cardiomyocyte function after application of the CCM
      signal was accompanied by an increase in the peak and integral of the Ca(2+)
      transient suggesting modulation of calcium cycling by CCM application. In a
      limited number of normal dogs, intermittent chronic delivery of the CCM signal
      for up to 7 days showed chronic maintenance of LV functional improvement. In
      conclusion, pre-clinical results to date with the Impulse Dynamics CCM signal
      indicate that this non-pharmacologic therapeutic modality can provide short-term
      positive inotropic support to the failing heart and as such, may be a useful
      adjunct in the treatment of advanced heart failure. Additional, long-term studies
      in dogs with heart failure are needed to establish the safety and efficacy of
      this therapeutic modality for the chronic treatment of this disease syndrome.

PMID- 11248769
TI  - The challenge of prediction and prevention of sudden cardiac death in congestive
      heart failure.

PMID- 11248768
TI  - Electrical modulation of cardiac contractility: clinical aspects in congestive
      heart failure.
AB  - Heart failure is a highly prevalent disease in western society. Drug therapies
      aimed at increasing myocardial contractility have been associated with decreased
      survival. Several short and mid term clinical studies have suggested adjuvant or
      alternative therapies to congestive heart failure using modified pacing
      techniques that were aimed to increase contractility (e.g. Paired pacing) or
      restore synchrony of contraction (biventricular pacing). While delivery of paired
      pacing was abandoned during the early 70's, biventricular pacing has recently
      emerged as an adjuvant treatment to limited group of congestive heart failure
      patients with aberrant left ventricular conduction. In this brief review, we
      describe our initial safety and efficacy experience in patients with heart
      failure using a novel non-stimulatory electrical approach to the delivery of
      positive inotropic therapy to the failing myocardium. The study suggests that
      unlike modified pacing techniques, delivery of the signal to the left ventricle
      during the refractory period resulted in a rapid increase in myocardial
      contractility and improved hemodynamic performance. The near instantaneous
      contractility improvement achieved by this type of stimulus was shown to be safe
      and effective independently of the primary cause of heart failure or the function
      of the conduction system. Unlike pharmacologic treatments, which have a
      relatively constant effect, use of electrical stimuli may prove useful as a new
      therapeutic modality in the treatment of heart failure with which contractility
      can be improved when and as needed.

PMID- 11248770
TI  - Review: The postural orthostatic tachycardia syndrome: current concepts in
      pathophysiology diagnosis and management.

PMID- 11248771
TI  - Linear ablation using an irrigated electrode electrophysiologic and histologic
      lesion evolution comparison with ablation utilizing a non-irrigated electrode.
AB  - OBJECTIVES: To characterize the electrophysiologic and histologic sequelae of
      linear atrial ablation utilizing an irrigated electrode. To compare "irrigated"
      lesions with lesions deployed using the same electrode in a non-irrigated mode.
      BACKGROUND: Previous reports of radiofrequency catheter ablation using an
      irrigated electrode have emphasized its favorable effect on lesion depth. We
      hypothesized that electrode irrigation would also benefit linear ablation of
      smooth atrial myocardium, a relatively superficial target. METHODS: In healthy
      pigs, lesions were deployed in the right and left atria. Acutely, lesions
      resulting from ablation using an irrigated electrode, with radiofrequency energy
      titration guided by electrogram amplitude reduction, were compared to lesions
      using the same electrode without irrigation, with energy titration guided by
      electrode thermometry. Irrigated lesions were also assessed serially. RESULTS:
      Acutely, irrigated lesions formed complete conduction barriers and were
      uncomplicated. In contrast, non-irrigated lesions formed complete conduction
      barriers but were frequently complicated, exhibiting endocardial charring,
      barotrauma, and pericardial damage. The rate and pattern of histologic evolution
      of irrigated lesions were uniform throughout each lesion; right and left atrial
      lesions healed similarly. During healing, 90 % of lesions remained complete
      conduction barriers and 10 % manifested single discrete conduction gaps where
      viable appearing myocytes bridged the lesion. CONCLUSIONS: Complete,
      uncomplicated linear lesions could be reliably deployed in either atrium with an
      irrigated electrode. Not all lesions remained complete barriers to conduction
      during their histologic evolution. Lesions deployed with the same electrode in a
      non-irrigated mode were complete but frequently complicated.

PMID- 11248772
TI  - Intracardiac echocardiographic evaluation of ventricular mural swelling from
      radiofrequency ablation in chronic myocardial infarction: irrigated-tip versus
      standard catheter.
AB  - INTRODUCTION: The production of larger, particularly deeper lesions may improve
      the success rate for radiofrequency (RF) ablation of post infarction ventricular
      tachycardia (VT). Therapeutic RF ablation causes left ventricular (LV) mural
      swelling. This swelling can be detected as increased wall thickness at the
      ablation site by intracardiac echocardiography (ICE) and correlates with
      pathologic lesion size. This study compared the extent of mural swelling caused
      by linear ablation lesions created with irrigated tip and standard RF ablation in
      a porcine model of healed anterior infarction. METHODS AND RESULTS: In
      anesthetized closed-chest swine ICE guided multiple RF applications to construct
      linear lesions at the border zone of the infarct region using an irrigated RF
      (n=6 swine) and a standard RF (n=6 swine) ablation catheter. 47 individual
      lesions were created with irrigated RF ablation; 57 lesions created with standard
      RF ablation. At all sites, wall thickness (measured at end-diastole Pre- and 1
      min Post-RF delivery) increased following either irrigated (p<0.0001) or standard
      (p<0.004) RF deployment. Irrigated RF ablation produced more mural swelling at
      border zone sites than standard RF ablation (wall thickness increase of 21.2
      versus 15.1 %, p<0.003). This difference was more pronounced at RF sites within
      the infarct (40.7 versus 12.0 %, p<0.0007). Thrombus formation or intramural
      explosion were not observed; surface crater formation was not more frequent with
      irrigated compared to standard RF ablation (14/47 versus 12/57 lesions, p=NS).
      CONCLUSION: Irrigated RF ablation may produce larger lesions than standard RF
      ablation, particularly for ablation targets within infarcted tissue. ICE imaging
      provides on line data about the characteristics of the developing lesion which
      may prove useful in dosing irrigated-tip RF energy application.

PMID- 11248773
TI  - Impact of consistent atrial pacing algorithm on premature atrial complexe number
      and paroxysmal atrial fibrillation recurrences in brady-tachy syndrome: a
      randomized prospective cross over study.
AB  - AIM OF THE STUDY: The Consistent Atrial Pacing (CAP) algorithm has been designed
      to achieve a high percentage of atrial pacing to suppress paroxysmal atrial
      fibrillation. The aim of our study was to compare the impact of DDDR+CAP versus
      DDDR pacing on paroxysmal atrial fibrillation recurrences and triggers in
      patients with Brady-Tachy Syndrome. METHODS: 61 patients, 23 M and 38 F, mean age
      75+/-9 y, affected by Brady-Tachy Syndrome, implanted with a DDDR pacemaker, were
      randomized to DDDR or DDDR+CAP pacing with cross over of pacing modality after 1
      month. RESULTS: 78 % of patients in DDDR pacing and 73 % in DDDR + CAP pacing
      (p=n.s.) were free from symptomatic paroxysmal atrial fibrillation recurrences.
      During DDDR+CAP pacing, the atrial pacing percentage increased from 77+/-29 % to
      96+/-7 % (p<0.0001). Automatic mode switch episodes/day were 0.73+/-1.09 in DDDR
      and 0.79+/-1.14 (p=n.s.) in DDDR+CAP. In patients with less than 50 % of atrial
      pacing during DDDR, automaticmode switch episodes/day decreased during DDDR+CAP
      from 1.13+/-1.59 to 0.23+/-0.32 (p<0.05) and in patients with less than 90 % from
      1.23+/-1.27 to 0.75+/-1.10 (p<0.001). The number of premature atrial complexes
      per day decreased during DDDR + CAP from 2665+/-4468 to 556+/-704 (p<0.02).
      CONCLUSION: CAP algorithm allowed continuous overdrive atrial pacing without
      major side effects. Triggers of paroxysmal atrial fibrillation induction, such as
      premature atrial complexes, were critically decreased. Paroxysmal atrial
      fibrillation episodes were reduced in patients with atrial pacing percentage
      lower than 90 % during DDDR pacing.

PMID- 11248774
TI  - Pacemaker repetitive nonreentrant ventriculoatrial synchronous rhythm. A review.
AB  - Ventriculoatrial (VA) synchrony during dual chamber pacing can occur in any
      patient who has the ability to sustain repeated retrograde conduction. If the
      retrograde P wave is sensed, the result will be an endless loop tachycardia or
      repetitive reentrant VA synchrony. VA synchrony can also occur when a dual
      chamber pacemaker does not sense a retrograde P wave within the postventricular
      atrial refractory period. In this situation if the normally suprathreshold atrial
      stimulus at the end of the atrial escape interval is continually delivered when
      the atrial myocardium is physiologically refractory, the result will be a
      repetitive nonreentrant VA synchronous rhythm. Repetitive nonreentrant VA
      synchrony may produce unfavorable hemodynamic consequences and the pacemaker
      syndrome. It represents an example of functional atrial undersensing combined
      with functional loss of atrial capture. Management requires modification of the
      programmed settings of the pacemaker and utilization of certain algorithms
      designed for other functions but nevertheless effective in this situation.

PMID- 11248775
TI  - Effect of different location of atrial lead position on nearfield and farfield
      electrograms in dual chamber pacemaker-defibrillators.
AB  - The normal functioning of dual chamber pacemaker-cardioverter defibrillator (AV
      pacer/ICD) may be affected by oversensing of the farfield R wave (FFRW) by the
      atrial channel. This study aimed to investigate whether placement of the AV
      pacer/ICD's atrial lead at a lateral (LAT) wall location compared to a medial
      (MED) location i.e. the appendage of the right atrium, would reduce the amplitude
      of FFRWs but not the nearfield atrial electrograms (AEGMs) during sinus rhythm
      (SR) and ventricular fibrillation (VF). In 17 patients, real time electrograms
      were recorded during SR and induced VF through the atrial lead initially at the
      MED and subsequently at the LAT location. In 10 patients the electrograms in SR
      were also recorded on a computerized data acquisition and recording system at
      different band-pass filter settings. Although FFRWs were recorded both at MED and
      LAT locations, they were much smaller, 3.5+/-4.1mm during SR and 1.7+/-2.2mm
      during VF at the LAT location. At 30-500Hz band-pass filter, lower amplitudes of
      FFRWs 0.14+/-0.09 mV were recorded at the LAT location. The V/A ratios of the
      amplitudes of FFRWs and AEGMs were smaller at the LAT location during SR and VF.
      The nearfield AEGMs were of similar amplitudes at the MED and LAT locations.
      These data indicate that lower amplitudes of FFRWs are recorded by placement of
      the atrial lead at the lateral wall of the right atrium. Oversensing of FFRWs may
      be prevented to improve functioning of the AV pacer-ICD.

PMID- 11248777
TI  - Case report: adenosine induced ventricular fibrillation in a patient with stable
      ventricular tachycardia.
AB  - Adenosine is frequently used in emergency departments and intensive care units
      for the termination of narrow complex tachycardias. Recently its utility in
      terminating wide complex tachycardias has been reported in the literature.
      Adenosine is generally felt to be a safe medication even though its proarrhythmic
      effects in the setting of narrow complex or supraventricular tachycardias have
      been well documented. Herein, we describe the first case to our knowledge of
      adenosine inducing ventricular fibrillation in a patient with a stable wide
      complex tachycardia that was subsequently proven to be ventricular tachycardia at
      electrophysiologic study.

PMID- 11248776
TI  - Case report: is this SVT or VT? An exception to the rule.
AB  - This case illustrates the difficulties sometimes encountered by clinicians when
      using algorithms in diagnosing a wide-complex tachycardia based on a 12-lead EKG.

PMID- 11248778
TI  - Case report: pulmonary embolism from thrombosis in a duplicated inferior vena
      cava developing after an electrophysiologic procedure.
AB  - Duplicated inferior cava (IVC) is an anomaly we rarely encounter during
      electrophysiologic procedures. We report a case with duplicated IVC who developed
      thrombosis of the left IVC following an electrophysiologic procedure, which
      resulted in an asymptomatic pulmonary embolism. It is speculated that several
      catheters placed in the torturous route through the left IVC caused either
      endothelial damage to the vessel wall, or hemostasis in the relatively narrow
      portion of the vessel, resulting in thrombus formation. Since the prevalence and
      characteristics of thrombo-embolic complications during electrophysiologic
      procedures in patients with a duplicated IVC remain unknown, we believe this case
      should be reported.

PMID- 11248779
TI  - Frequency-dependent electrophysiological effect of ibutilide on human atrium and
      ventricle.
AB  - Most of the class III antiarrhythmic agents developed in recent years blocks the
      rapid component of delayed rectifier potassium current (IKr). IKr blocker shows
      reverse use-dependency and also may cause torsades de pointes at slower heart
      rate. Ibutilide fumarate, a novel class III antiarrhythmic agent, increases
      window Na(+) current at the action potential plateau phase. We studied the rate
      dependent effect of ibutilide on the electrophysiological parameters of human
      atrium and ventricle. Franz catheter and a pacing catheter were placed closely in
      the high right atrium and right ventricular apex to record monophasic action
      potentials (MAP) during pacing at cycle length (PCL) of 600 ms and 350 ms in
      eight patients who underwent electrophysiological study. MAP duration of right
      atrium (RA-MAPD) and right ventricle (RV-MAPD), effective refractory period of RA
      and RV (RA-ERP and RV-ERP), intra-atrial conduction time (IACT) and intra
      ventricular conduction time (IVCT) were measured before and after intravenous
      administration of ibutilide (0.01 mg/kg up to 1mg). A conduction time from RA
      pacing spike to distal coronary sinus potential was used to measure IACT, while
      QRS duration of surface ECG during RV pacing was used to measure IVCT. Ibutilide
      prolonged RA-MAPD by 60 ms at PCL 600 ms and by 53 ms at PCL 350 ms; RV-MAPD by
      48 ms at PCL 600 ms and by 55 ms at PCL 350 ms. Ibutilide did not affected RA and
      RV-ERP/MAPD ratio, IACT, and IVCT. Ibutilide prolongs MAPD and ERP of human
      atrium and ventricle without reverse use-dependency.

PMID- 11248780
TI  - Transseptal left heart catheterization for cardiac ablation procedures.
AB  - Transseptal left heart catheterization has been performed as an alternative to
      the retrograde approach since 1958. However, this procedure can result in life
      threatening complications, some of which may occur because of insufficient
      anatomical landmarks. Accordingly, we sought to assess the safety and efficacy of
      a new transseptal left heart catheterization technique designed for ablation
      procedures. Specifically, we examined whether electrode catheters could be used
      as anatomical landmarks, permitting identification of the aortic root and other
      critical structures. RESULTS: One hundred and eight consecutive patients
      underwent transseptal left heart catheterization under biplane fluoroscopy during
      catheter ablation. Electrode catheters positioned in the right atrial appendage,
      His bundle region, and coronary sinus were used as anatomical landmarks to guide
      the transseptal unit to the fossa ovalis. The angles of the right anterior and
      left anterior oblique projections were selected in each patient based on the
      orientation of the His bundle and coronary sinus catheters. Transseptal left
      heart catheterization was successfully performed in all patients without
      complications. In contrast to previous reports, the direction of the needle at
      the successful puncture site in the last 96 patients varied substantially: 2
      o'clock in 13 patients (13 %); 3 o'clock in 43 patients (45 %); and 4 o'clock in
      40 patients (42 %). CONCLUSION: The use of electrode catheters as anatomical
      landmarks and biplane fluoroscopy facilitates transseptal catheterization. This
      approach can be used safely during catheter ablation procedures.

PMID- 11248781
TI  - Transseptal catheterization for the electrophysiologist: modification with a
      "view".

PMID- 11248782
TI  - Electroanatomical Mapping (CARTO) of ectopic atrial tachycardia: impact of
      bipolar and unipolar local electrogram annotation for localization the focal
      origin.
AB  - Electroanatomical Mapping (CARTO) allows a tridimensional localization of ectopic
      atrial tachycardia (EAT). No standardized recommendation exists for annotation
      the local activation time in EAT using this new technology. In the present study
      bipolar local electrogram were used for CARTO guided RF ablation of EAT. In
      comparison the same maps were retrospectively analyzed by annotation the unipolar
      local electrogram. METHODS: In 15 consecutive patients (6m, 51+/-14 y) with EAT
      CARTO mapping was guided by annotation the earliest onset of the bipolar local
      electrogram. Following successful RF ablation the obtained EAT maps were
      subsequently evaluated by annotation of the earliest steepest negative intrinsic
      deflection of the unipolar local electrogram. Both CARTO maps were compared with
      regard to the region of focal EAT origin. RESULTS: RF ablation of all 15 EAT foci
      guided by annotation the bipolar local electrogram with CARTO was successful with
      a median of 3 [1-18] pulses and a median fluoroscopy time of 10 min [4-25]. All
      but one focus was located in the right atrium: posterior to posteroinferior
      region of the terminal crest in 6, septal region in 5, anterior superior region
      in 3 cases. One left sided EAT was located at the septum. The bipolar CARTO map
      demonstrated a "small territory" location of earliest activation (extension of
      the focus < or =0.4 cm(2)) in 14 out of 15 patients. In a single patient the
      bipolar map showed several sites of earliest local activation (extension >0.4
      cm(2)). On the other side the retrospectively achieved unipolar maps demonstrated
      an extended region of earliest local activation in 6 out of 15 patients (>0.4
      cm(2)). CONCLUSIONS: CARTO maps of EAT by annotation the earliest onset of the
      bipolar local electrogram provide an efficacious guide for location the focal
      origin. Extended regions of earliest local activation in EAT might be rather
      determined by annotation the unipolar in comparison to the bipolar local
      electrogram.

PMID- 11248783
TI  - Apparent bidirectional conduction block following radiofrequency catheter
      ablation of typical atrial flutter.
AB  - OBJECTIVE: The purpose of this study is to determine the reliability of
      activation sequence mapping in assessing the presence of bidirectional conduction
      block (BCB) in typical atrial flutter (AFL) ablation. INTRODUCTION:
      Radiofrequency ablation (RFA) can cure typical AFL by creating BCB across the
      right atrial isthmus. Effective conduction block across this region can prevent
      AFL recurrence, but accurate assessment of isthmus conduction may be flawed.
      METHODS: BCB was measured before and after RFA by pacing at multiple rates on
      both sides of the isthmus during sinus rhythm. Pacing was performed from a low
      lateral tricuspid annulus site (proximal to the isthmus) and a coronary sinus Os
      site (distal to the isthmus), while recording simultaneously from 8-10 right
      atrial sites bordering the isthmus (4-5 free wall sites; 4-5 septal sites) as
      well as from an isthmus site. After ablation reinduction of atrial flutter was
      attempted from both sides of the block with rapid atrial pacing after BCB was
      established in all patients. In some patients lines of conduction block were
      evident at the isthmus (using the ablation catheter to map). RESULTS: Of 65
      patients undergoing RFA of AFL, 59 had typical AFL. In all 59 patients, BCB was
      demonstrated at all pacing cycle lengths 30 min after RFA applications. In 6 of
      these 59, AFL was inducible with atrial pacing despite apparent BCB. Further RFA
      resulted in non inducibility in all 6 patients. In the remaining 53/59 patients,
      BCB was associated with noninducibility at 30 min. A total of 8 recurrences were
      seen during a mean 19.3 +/- 8.3 (SD) month follow-up. CONCLUSION: Apparent BCB as
      determined by activation sequence mapping outside of the isthmus is an excellent
      marker, but, as measured, may be a misleading method of assessing the presence or
      absence of conduction through the isthmus. It is necessary to attempt reinduction
      of AFL after apparent success. Elimination of typical AFL does not preclude other
      AFLs.

PMID- 11248784
TI  - Hippocrates of Cos (466-377 BC) and the Hippocratic oath.

PMID- 11248785
TI  - Glycoprotein IIb/IIIa Inhibition as an adjunct to rescue angioplasty after failed
      fibrinolysis.

PMID- 11248786
TI  - Myocardial infarction in patients with normal coronary arteries: proposed
      pathogenesis and predisposing risk factors.

PMID- 11248787
TI  - Antithrombotic effect of LB-30057 (CI-1028), a new synthetic thrombin inhibitor,
      in a rabbit model of thrombosis: comparison with inogatran.
AB  - LB-30057 (CI-1028) is a novel, orally bioavailable, direct thrombin inhibitor
      with a Ki of 0.38 nM against human thrombin. The effects of LB-30057 on thrombus
      formation and hemostasis were evaluated in a veno-venous shunt model of
      thrombosis in rabbits, and compared with inogatran, another direct inhibitor of
      thrombin. Each compound was studied at 5 or 6 different doses with 5 or 6 rabbits
      in each group. After administration as a bolus i.v. injection followed by
      continuous infusion, both LB-30057 and inogatran dose-dependently inhibited
      thrombus formation, which was measured as an increase in time to occlusion (TTO)
      and a decrease in thrombus weight. Both compounds also improved vena caval blood
      flow and reduced the overall incidence of thrombotic occlusion. LB-30057
      significantly prolonged TTO from 23 +/- 4 min (before dose) to 110 +/- 10 min at
      the highest dose (0.7 mg/kg + 47 microg/kg/min) (p < 0.001), and reduced thrombus
      weight from 57 +/- 2 mg to 15 +/- 5 mg (p < 0.001). Occlusive thrombus formed in
      only one of six rabbits that received the highest dose of LB-30057 (vs. 13/13 in
      the control group, p < 0.01). At the dose that produced the maximum
      antithrombotic effect (0.7 mg/kg + 47 microg/kg/min), LB-30057 increased aPTT and
      bleeding time approximately 2-and 2.5-fold above baseline, respectively. On a
      gravimetric basis, LB-30057 and inogatran displayed comparable in vivo
      antithrombotic efficacy. When compared to equally effective anti thrombotic doses
      of inogatran, LB-30057 caused less prolongation in aPTT, had no effect on PT, and
      tended to have less of effect on bleeding time. These results indicate that LB
      30057 is an effective antithrombotic compound and it appears to have a better
      benefit/risk profile than inogatran in this experimental model.

PMID- 11248788
TI  - Trousseau's syndrome treated with long-term subcutaneous lepirudin (case report
      and review of the literature).
AB  - We report here a case of recurrent venous and arterial thromboembolism,
      Trousseau's syndrome, in a cancer patient who developed heparin-induced
      thrombocytopenia. She was treated with lepirudin and after establishing the
      patient-specific half-life for subcutaneous lepirudin, she was successfully
      maintained on this therapy for more than eight months. To our knowledge this case
      represents the longest reported use of subcutaneous lepirudin.

PMID- 11248789
TI  - Pharmacokinetics and pharmacodynamics of low-molecular-weight heparins and
      glycoprotein IIb/IIIa receptor antagonists in renal failure.
AB  - Data regarding the use of low-molecular-weight heparins (LMWHs) and glycoprotein
      (GP) IIb/IIIa receptor antagonists in patients with renal failure are limited.
      Renal failure has the potential to increase the risk of adverse drug events
      associated with LMWHs and GP IIb/IIIa receptor antagonists. This is due to
      changes in the pharmacokinetic and pharmacodynamic profiles of these agents in
      patients with renal failure. Until more data are available, clinicians should
      consider alternative therapies in this patient population.

PMID- 11248791
TI  - Platelet glycoprotein IIb/IIIa inhibitors combined with fibrinolytic agents to
      treat acute myocardial infarction.
AB  - Fibrinolytic drugs given within 6-12 h of onset of symptoms have reduced
      mortality by approximately 30%. However, even the most efficacious regimens are
      associated with only a 55% reperfusion rate at 90 min. In contrast, primary
      angioplasty (without fibrinolysis) yields to reperfusion in 75-95% of cases. This
      therapy, when compared with fibrinolysis, is associated with lower early
      mortality and reinfarction rates. Therefore, there is a need to find a therapy
      that would have the speed and ease of administration of intravenous lysis and the
      efficacy of primary angioplasty in re-establishing normal myocardial tissue
      perfusion. This article will review the rationale for the use of partial-dose
      lytic agents combined with platelet glycoprotein IIb/IIIa inhibitors for the
      treatment of acute myocardial infarction. The available and upcoming data on this
      subject will also be reviewed.

PMID- 11248792
TI  - A fond farewell.

PMID- 11248793
TI  - Working together for robust immune responses in the elderly.

PMID- 11248794
TI  - The most elegant immunological experiment of the XIX century.
AB  - When we remember that immunology was barely a decade old and knowledge of
      circulating antibodies only two years old when Ehrlich performed the experiments
      described, we can appreciate the inventiveness of his experimental designs. With
      little wasted effort he planned simple and rapid experiments to answer crucial
      questions about the mechanism of passive transfer of antibody from mother to
      fetus to suckling young. Most remarkable and difficult were the foster mother
      experiments, as anyone who has tried these with mice will attest. But they were
      judged to be critical and thus were pursued with ultimate success. These
      experiments would not be improved upon for 60 years, when the identification of
      immunoglobulin classes made differential transplacental and transglandular
      passage of immunoglobulins an object of interest. To conceive of studying the
      kinetics of the immune response by measuring changes in antibody concentration in
      the milk of lactating animals was yet another demonstration of the fertile
      imagination that had contributed so much to histology and hematology, and would
      soon contribute equally to experimental oncology and to scientific pharmacology.

PMID- 11248795
TI  - Now you see it, now you don't!

PMID- 11248796
TI  - Intertwining proteins in thymocyte development and cancer.

PMID- 11248797
TI  - Paneth cells--guardians of the gut cell hatchery.

PMID- 11248790
TI  - Candidate genes and confirmed genetic polymorphisms associated with
      cardiovascular diseases: a tabular assessment.

PMID- 11248798
TI  - gp96--the immune system's Swiss army knife.

PMID- 11248800
TI  - Immunology highlights from the recent literature.

PMID- 11248799
TI  - Innate immunity--beginning to fulfill its promise?

PMID- 11248801
TI  - Homeostasis of alpha beta TCR+ T cells.
AB  - Cytokines contribute to T cell homeostasis at all stages of T cell existence.
      However, the particular cytokine involved varies as T cells progress from a naive
      through an activated to a memory state. In many cases the important cytokines are
      members of the interleukin 2 subfamily of the short-chain type I cytokines. A
      case is made for the idea that the evolutionary divergence of the short-chain
      family allowed for concurrent divergence in leukocytes.

PMID- 11248802
TI  - Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response
      to bacteria.
AB  - Paneth cells in mouse small intestinal crypts secrete granules rich in
      microbicidal peptides when exposed to bacteria or bacterial antigens. The dose
      dependent secretion occurs within minutes and alpha-defensins, or cryptdins,
      account for 70% of the released bactericidal peptide activity. Gram-negative
      bacteria, Gram-positive bacteria, lipopolysaccharide, lipoteichoic acid, lipid A
      and muramyl dipeptide elicit cryptdin secretion. Live fungi and protozoa,
      however, do not stimulate degranulation. Thus intestinal Paneth cells contribute
      to innate immunity by sensing bacteria and bacterial antigens, and discharge
      microbicidal peptides at effective concentrations accordingly.

PMID- 11248803
TI  - Ligands for the murine NKG2D receptor: expression by tumor cells and activation
      of NK cells and macrophages.
AB  - Natural killer (NK) cells attack tumor and infected cells, but the receptors and
      ligands that stimulate them are poorly understood. Here we report the expression
      cloning of two murine ligands for the lectin-like receptor NKG2D. The two
      ligands, H-60 and Rae1 beta, are distant relatives of major histocompatibility
      complex class I molecules. NKG2D ligands are not expressed by most normal cells
      but are up-regulated on numerous tumor cells. We show that mouse NKG2D is
      expressed by NK cells, activated CD8+ T cells and activated macrophages.
      Expression of either NKG2D ligand by target cells triggers NK cell cytotoxicity
      and interferon-gamma secretion by NK cells, as well as nitric oxide release and
      tumor necrosis factor alpha transcription by macrophages. Thus, through their
      interaction with NKG2D, H-60 and Rae1 beta are newly identified potent
      stimulators of innate immunity.

PMID- 11248804
TI  - C3d enhancement of antibodies to hemagglutinin accelerates protection against
      influenza virus challenge.
AB  - The ability of the C3d component of complement to enhance antibody responses and
      protective immunity to influenza virus challenges was evaluated using a DNA
      vaccine encoding a C3d fusion of the hemagglutinin (HA) from influenza virus.
      Plasmids were generated that encoded a transmembrane HA (tmHA), a secreted form
      of HA (sHA), or a sHA fused to three tandem copies of the murine homologue of the
      C3d (sHA-3C3d). Analysis of the titers, avidity maturation, and hemagglutinin
      inhibition activity of raised antibody revealed that immunizations with sHA-3C3d
      DNA accelerated both the avidity maturation of antibody to HA and the appearance
      of hemagglutinin-inhibition activity. These accelerated antibody responses
      correlated to a more rapid appearance of protective immunity. They also
      correlated to complete protection from live virus challenge by a single
      vaccination at a dose ten times lower than the protective dose for non-C3d forms
      of HA.

PMID- 11248805
TI  - IL-18 induction of IgE: dependence on CD4+ T cells, IL-4 and STAT6.
AB  - Overproduction of immunoglobulin E (IgE) and T helper cell type 2 (TH2)
      cytokines, including interleukin 4 (IL-4), IL-5 and IL-13, can result in allergic
      disorders. Although it is known that IL-4 is critical to the polarization of
      naive CD4+ T cells to a TH2 phenotype, both in vitro and in many in vivo systems,
      other factors that regulate in vivo IL-4 production and TH2 commitment are poorly
      understood. IL-18, an IL-1-like cytokine that requires cleavage with caspase-1 to
      become active, was found to increase IgE production in a CD4+ T cells-, IL-4- and
      STAT6-dependent fashion. IL-18 and T cell receptor-mediated stimulation could
      induce naive CD4+ T cells to develop into IL-4-producing cells in vitro. Thus,
      caspase-1 and IL-18 may be critical in regulation of IgE production in vivo,
      providing a potential therapeutic target for allergic disorders.

PMID- 11248806
TI  - SCL and LMO1 alter thymocyte differentiation: inhibition of E2A-HEB function and
      pre-T alpha chain expression.
AB  - Cooperation between the stem cell leukemia (SCL) transcription factor and its
      nuclear partners LMO1 or LMO2 induces aggressive T cell acute lymphoblastic
      leukemia when inappropriately expressed in T cells. This study examined the
      cellular and molecular targets of the SCL-LMO complex at the preleukemic stage.
      We show that SCL and its partners are coexpressed in the most primitive
      thymocytes. Maturation to the pre-T cell stage is associated with a down
      regulation of SCL and LMO1 and LMO2, and a concomitant up-regulation of E2A and
      HEB expression. Moreover, enforced expression of SCL-LMO1 inhibits T cell
      differentiation and recapitulates a loss of HEB function, causing a deregulation
      of the transition checkpoint from the CD4-CD8- to CD4+CD8+ stages. Finally, we
      identify the gene encoding pT alpha as a downstream target of HEB that is
      specifically repressed by the SCL-LMO complex.

PMID- 11248807
TI  - Epitope affinity for MHC class I determines helper requirement for CTL priming.
AB  - We show here that priming and memory generation of antigen-specific CD8+
      cytotoxic T lymphocytes (CTL) does not require help if the immunogen binds major
      histocompatibility complex (MHC) class I molecules with high affinity. This
      conclusion was based on the study of three chemically distinct optimal length CTL
      epitopes with high affinity for the restriction element Kb. In contrast, when two
      subdominant epitopes with intermediate MHC binding affinity were studied, either
      a class II MHC-restricted T helper cell epitope or administration of antibody to
      CD40 was required to obtain significant CTL priming. Depending on the epitope,
      one source of help was much more efficient than the other.

PMID- 11248808
TI  - CD91: a receptor for heat shock protein gp96.
AB  - Antigen presenting cells (APCs) can take up exogenous antigenic peptides
      chaperoned by heat shock protein gp96 and re-present them through the endogenous
      pathway on their major histocompatibility class I molecules. The high efficiency
      of this process has been attributed previously to a receptor for gp96 on APCs.
      The CD91 molecule (also called alpha 2-macroglobulin receptor or the low density
      lipoprotein-related protein) is shown here to be a cell surface receptor for the
      heat shock protein gp96. CD91 binds gp96 directly, rather than through another
      ligand for CD91. The previously known CD91 ligand, alpha 2-macroglobulin,
      inhibits re-presentation of gp96-chaperoned antigenic peptides by macrophages, as
      do antibodies to CD91. As gp96 is exclusively intracellular and is released as a
      result of necrotic but not apoptotic cell death, we propose that CD91 acts as a
      sensor for necrotic cell death.

PMID- 11248809
TI  - Concentration of MHC class II molecules in lipid rafts facilitates antigen
      presentation.
AB  - The plasma membranes of eukaryotic cells are not uniform and possess distinct
      cholesterol- and sphingolipid-rich raft microdomains that are enriched in
      proteins known to be essential for cellular function. Lipid raft microdomains are
      important for T cell receptor (TCR)-mediated activation of T cells. However, the
      importance of lipid rafts on antigen presenting cells (APCs) and their role in
      major histocompatibility (MHC) class II-restricted antigen presentation has not
      been examined. MHC class II molecules were found to be constitutively present in
      plasma membrane lipid rafts in B cells. Disruption of these microdomains
      dramatically inhibited antigen presentation at limiting concentrations of
      antigen. The inhibitory effect of raft disruption on antigen presentation could
      be overcome by loading the APCs with exceptionally high doses of antigen, showing
      that raft association concentrates MHC class II molecules into microdomains that
      allow efficient antigen presentation at low ligand densities.

PMID- 11248810
TI  - Costimulatory blockade by the induction of an endogenous xenospecific antibody
      response.
AB  - Xenogeneic tissues induce vigorous T cell immunity, reflecting the ability of
      costimulatory molecules to function across species barriers. We describe a
      strategy to inhibit costimulation that exploits species differences using the
      model of porcine pancreatic islet transplantation into mice. Mice were immunized
      with chimeric peptides that contained a known T cell epitope and selected
      sequences of the porcine costimulatory molecule CD86. This resulted in anti
      peptide antibody responses that recognized intact porcine CD86, blocked
      costimulation by porcine CD86 but not murine CD86 in vitro, and prolonged the
      survival of porcine islet grafts in vivo. This strategy of inducing endogenous
      donor-specific costimulatory blockade has potential clinical applicability.

PMID- 11248811
TI  - BLIMP-1: trigger for differentiation of myeloid lineage.
AB  - B lymphocyte-induced maturation protein-1 (BLIMP-1 or PRDI-BF1) is induced when
      bone marrow-derived progenitors differentiate in response to macrophage-colony
      stimulating factor (M-CSF) and is present in peripheral blood monocytes and
      granulocytes. BLIMP-1 is also induced during differentiation of U937 and HL-60
      cells into macrophages or granulocytes. Induction of BLIMP-1 mRNA during
      macrophage differentiation of U937 and HL-60 shows a biphasic pattern.
      Overexpression of BLIMP-1 is sufficient to initiate macrophage differentiation of
      U937 cells whereas blocking endogenous BLIMP-1 inhibits differentiation. One
      target of BLIMP-1-dependent transcriptional repression in U937 cells is c-myc,
      providing an explanation for cessation of cell division. Thus BLIMP-1 is a key
      regulator of terminal differentiation in two separate hematopoietic lineages:
      myeloid cells and B lymphocytes.

PMID- 11248812
TI  - Predictors of recurrent herpes simplex virus keratitis. Herpetic Eye Disease
      Study Group.
AB  - PURPOSE: Determinants of the natural history of recurrent herpes simplex virus
      (HSV) keratitis have not been consistently established. We assessed how previous
      HSV eye disease affects the risk of recurrent HSV keratitis and evaluated whether
      demographic and other variables play any predictive role. METHODS: Three hundred
      forty-six patients in the placebo group of the Herpetic Eye Disease Study's
      Acyclovir Prevention Trial who had experienced an episode of HSV eye disease in
      the previous year were followed up for 18 months. Recurrences were categorized
      according to the type of involvement. Relative rates of recurrence were compared
      for categories of demographic variables, types and number of previous ocular HSV
      episodes, previous nonocular HSV infection, and month of the year. RESULTS: Fifty
      eight (18%) of the 346 patients developed epithelial keratitis and 59 (18%)
      developed stromal keratitis during the 18 months of follow-up. Previous
      epithelial keratitis did not significantly affect the risk of epithelial
      keratitis (p = 0.84). In contrast, previous stromal keratitis increased the risk
      of stromal keratitis 10-fold (p < 0.001), and the risk was strongly related to
      the number of previous episodes (p < 0.001). Age, gender, ethnicity, and
      nonocular herpes were not significantly associated with recurrences, and no
      seasonal effects were observed. CONCLUSION: Among patients who experienced active
      ocular HSV disease in the previous year, a history of epithelial keratitis was
      not a risk factor for recurrent epithelial keratitis. In contrast, previous,
      especially multiple, episodes of stromal keratitis markedly increased the
      probability of subsequent stromal keratitis.

PMID- 11248813
TI  - Corneal graft outcome study.
AB  - PURPOSE: To determine overall 2- and 5-year corneal graft survival rates and to
      identify risk factors for corneal graft failure in our patient population.
      METHODS: A retrospective chart review of 696 patients undergoing corneal
      transplantation performed by a single surgeon at The Toronto Western Hospital
      over a 7.5-year period. RESULTS: A total of 468 eyes met the inclusion criteria
      for this study. Overall, the 2- and 5-year graft survival rates were 78.8% and
      64.5%, respectively. In a univariate analysis, patient age, gender, history of
      glaucoma, preoperative diagnosis, type of operative procedure, and postoperative
      factors all were shown to be significantly associated with graft survival. In a
      multivariate analysis, six independent predictors of graft failure were
      identified: preoperative diagnosis, neovascularization of the graft, the presence
      of peripheral anterior synechiae, gender, occurrence of one or more rejection
      episodes, and age of the recipient at the time of corneal transplantation.
      CONCLUSIONS: Risk of graft failure can vary substantially within a population of
      patients receiving a corneal transplant. The outcomes of this study concur with
      the risk factors for corneal graft failure in the literature and can be used as
      prognostic guidelines for both surgeons and patients.

PMID- 11248814
TI  - Penetrating keratoplasty in iridocorneal endothelial syndrome.
AB  - PURPOSE: To evaluate the clinical outcome of penetrating keratoplasty (PK) in
      iridocorneal endothelial (ICE) syndrome. METHODS: Clinical charts of patients who
      underwent penetrating keratoplasty for ICE syndrome between 1985 and 1999 were
      reviewed retrospectively. Glaucoma control, best corrected visual acuity pre- and
      post-PK, graft clarity, graft rejection episodes, improvement in pain, and
      additional procedures were analyzed. RESULTS: Fourteen cases were reviewed with
      an average follow-up of 58 months after PK. Initial grafts failed in seven
      patients (50%), in six cases because of rejection, and one owing to endothelial
      failure without signs of rejection. Repeat PKs were performed in six patients. At
      final follow-up, 12 grafts were clear. Glaucoma was controlled pre- and post-PK
      (average intraocular pressure, 16 mmHg for both eyes). Pre-PK, eight patients
      were using glaucoma medicines and nine had had glaucoma surgery. At the end of
      the follow-up, seven patients were using glaucoma medicines; six patients
      required glaucoma surgery after their initial PK. At the final follow-up visit,
      visual acuity in three patients (21%) was 20/40 or better, it ranged from 20/50
      to 20/100 in four patients (29%) and 20/200 to 20/400 in five patients (36%), and
      in two patients with failed grafts (14%) it was counting fingers or worse.
      CONCLUSION: Clear grafts were achieved in 12 cases, although six patients (43%)
      underwent repeat PKs. All patients had glaucoma, which was controlled before and
      after PK by medical treatment and surgical procedures. Favorable outcomes can be
      achieved in patients with ICE syndrome but may require multiple corneal and
      glaucoma procedures.

PMID- 11248815
TI  - Changing indications for penetrating keratoplasty in Taiwan from 1987 to 1999.
AB  - PURPOSE: To determine the leading indications for penetrating keratoplasty and to
      identify changing trends in these indications during the past 12 years. METHODS:
      We retrospectively performed a chart review of the hospital records of all
      patients undergoing penetrating keratoplasty at the National Taiwan University
      Hospital during a 12-year period (1987-1999). When possible, the clinical
      indication was corroborated by the pathologic report. RESULTS: A total of 770
      corneal transplants were performed. The leading indications for penetrating
      keratoplasty. in order of decreasing frequency, were corneal scars (27.9%),
      regraft (21.0%), acute necrotizing and ulcerative keratitis (17.9%), pseudophakic
      or aphakic bullous keratopathy (17.6%), Fuchs' dystrophy (4.5%), and keratoconus
      (2.5%). A trend of increasing frequency of regraft and acute necrotizing and
      ulcerative keratitis, a decreasing frequency of corneal scar, and an initially
      decreasing then increasing frequency of pseudophakic and aphakic bullous
      keratopathy were found during the 12-year study period. Acute necrotizing and
      ulcerative keratitis was found to be the most frequent indication for regraft.
      CONCLUSION: In this series, corneal scars, regraft, and acute necrotizing and
      ulcerative keratitis were the leading indications for penetrating keratoplasty. A
      changing incidence of pseudophakic and aphakic bullous keratopathy noted during
      the study period was related to the type of intraocular lens implanted and the
      method of cataract surgery performed. This study found a comparatively high
      frequency of acute necrotizing and ulcerative keratitis and an extremely low
      frequency of keratoconus compared with previous reports.

PMID- 11248816
TI  - Impression cytology-proven corneal stem cell deficiency in patients after
      surgeries involving the limbus.
AB  - PURPOSE: To report three cases of limbal stem cell deficiency (confirmed by
      impression cytology) that followed multiple pterygium surgeries and therapeutic
      penetrating keratoplasty. METHODS: The first case, after multiple pterygium
      surgeries, presented with corneal scarring and thickened epithelium with
      vascularization sparing the central cornea in the right eye and involving the
      entire cornea in the left eye. The second case presented with superficial
      scarring and extensive vascularization after failed therapeutic graft performed
      for a large perforated corneal ulcer. The third case was a clear graft performed
      for a progressing fungal ulcer with signs of conjunctivalization
      inferotemporally. Limbal stem cell deficiency was clinically suspected in all of
      these cases. RESULTS: Goblet cells with mucin globules were found on the corneal
      surface by impression cytology in all three cases. CONCLUSIONS: We report three
      cases of limbal stem cell deficiency (proven by impression cytology) that
      followed multiple pterygium surgeries and therapeutic penetrating keratoplasty.
      Surgical insult to the limbus is the predisposing factor for stem cell damage in
      these cases. Involvement of the limbus by infection and use of intensive
      medications are probable contributing factors for stem cell damage in cases of
      therapeutic penetrating keratoplasty.

PMID- 11248817
TI  - Immunologic rejection of the central graft after limbal allograft transplantation
      combined with penetrating keratoplasty.
AB  - PURPOSE: To study the incidence and prognosis of immunologic rejection of the
      central graft after limbal allograft transplantation (keratolimbal allograft
      transplantation [KLAT]) combined with penetrating keratoplasty (PKP). METHODS:
      Endothelial rejection in central penetrating graft after simultaneous KLAT and
      PKP using the same donor cornea was retrospectively studied. Incidence,
      reversibility, prognosis, and changes in limbal grafts were examined. RESULTS:
      Forty-five eyes underwent simultaneous PKP and KLAT. Endothelial rejection of the
      central graft was found in 16 eyes (35.6%). At last examination, 10 grafts
      (62.5%) restored clarity after immunosuppressive therapy. During rejection
      episodes, four eyes showed engorgement of vessels in limbal grafts, which existed
      before the episodes. Only one eye developed neovascularization with mild edema of
      the limbal grafts; however, no other limbal grafts showed abnormalities on
      biomicroscopy. No epithelial changes were noted, and 14 grafts (87.5%) were
      covered by corneal epithelium after the rejection. CONCLUSION: Approximately one
      third of eyes had endothelial rejection in the central graft after simultaneous
      KLAT and PKP. Abnormalities suggestive of rejection in the limbal grafts were
      seldom observed in these eyes, suggesting that immunologic response was different
      in central and limbal grafts.

PMID- 11248818
TI  - Recovery of uncorrected visual acuity after laser in situ keratomileusis or
      photorefractive keratectomy for low myopia.
AB  - PURPOSE: To compare uncorrected visual acuity and refractive error in patients
      undergoing photorefractive keratectomy (PRK) and laser in situ keratomileusis
      (LASIK) between 1 week and 6 months after surgery. METHODS: All eyes underwent
      PRK or LASIK with the VisX StarS2 excimer laser. We retrospectively analyzed data
      from 77 random eyes of 77 patients in the PRK group and 76 eyes of 76 patients in
      the LASIK group. All eyes had a low myopic refractive error (spherical equivalent
      range, -0.88 diopters (D) to -5.13 D; mean PRK. -2.8 +/- 0.20 D: LASIK, -2.5 +/-
      0.22 D). Uncorrected visual acuity and manifest refractive error were evaluated 1
      week, 1 month, and 6 months after surgery. RESULTS: Each eye undergoing PRK was
      paired with an eye undergoing LASIK for a similar level of spherical equivalent.
      Mean uncorrected visual acuity after 1 week was 0.85 +/- 0.06 (20/25, logMAR 0.12
      +/- 0.04) for the PRK group and 1.01 +/- 0.06 (20/20, logMAR 0.01 +/- 0.03) for
      the LASIK group (p < 0.001). Mean spherical equivalent after 1 week was 0.23 +/-
      0.12 D for the PRK group and -0.02 +/- 0.07 D for the LASIK group (p = 0.02).
      Mean uncorrected visual acuity after 1 month was 1.03 +/- 0.05 (20/20, logMAR
      0.02 +/- 0.03) for the PRK group and 1.05 +/- 0.05 (20/20. -0.02 +/- 0.03) for
      the LASIK group (p = 0.16). Mean spherical equivalent after I month was 0.19 +/-
      0.10 D for the PRK group and -0.02 +/- 0.09 D for the LASIK group. This
      difference was statistically significant (p = 0.02), but was unlikely to be
      clinically significant. Mean uncorrected visual acuity after 6 months was 1.05 +/
      0.06 (20/20, logMAR -0.01 +/- 0.03) for the PRK group and 1.06 +/- 0.05 (20/20,
      logMAR -0.14 +/- 0.03) for the LASIK group (p = 0.41). Mean spherical equivalent
      after 6 months was 0.02 +/- 0.08 D for the PRK group and 0.00 +/- 0.08 D for the
      LASIK group (p = 0.35). CONCLUSION: Uncorrected visual acuity 1 week after
      surgery is significantly better in eyes undergoing LASIK than in eyes undergoing
      PRK. Both procedures provide functional vision by 1 week after surgery. The
      difference does not relate to refractive error, which was similar between the two
      groups, but to differences in healing of the epithelium. By 1 month after
      surgery, there is no difference in mean uncorrected visual acuity between eyes
      that undergo PRK or LASIK for low myopia.

PMID- 11248819
TI  - Recurrent corneal erosion after laser in situ keratomileusis.
AB  - PURPOSE: To describe how laser-assisted in situ keratomileusis (LASIK) may induce
      recurrent corneal erosion (RCE) syndrome and the preventive measures for avoiding
      this complication. METHODS. A case series was used. RESULTS: We report the
      development of RCE syndrome in eight eyes of six patients after LASIK. In five
      cases, the RCE was triggered by epithelial trauma at the time of the LASIK
      procedure, as evidenced by the observation of RCE occurring at the same site as
      the initial epithelial disturbance. In case 6, RCE occurred with undiagnosed
      basement membrane dystrophy. The patients responded to treatment with ocular
      lubricants with one patient undergoing penetrating keratoplasty for RCE after
      LASIK. CONCLUSION: LASIK can induce or precipitate RCE, and RCE should perhaps be
      included as a potential complication in the informed consent process. It is
      important to minimize epithelial damage to prevent RCE after LASIK, and measures
      to reduce this include adequate irrigation of the corneal surface immediately
      before the microkeratome pass and careful attention to flap epithelium during
      flap replacement. Cases in which loose epithelium is noted after LASIK should be
      identified as potential RCE cases, and extra care should be taken for subsequent
      enhancement procedures or LASIK of the second eye.

PMID- 11248820
TI  - Ocular morbidity associated with airbag deployment: a report of seven cases and a
      review of the literature.
AB  - PURPOSE: To review ocular injuries secondary to airbag deployment that were seen
      in our institution and were reported in the literature. METHODS: Patients
      examined at our institution between 1997 and 2000 were evaluated for ocular
      injuries caused by airbags. A review of the medical literature using Medline was
      performed. All reports involving ocular injuries secondary to airbags were
      included in this study. RESULTS: Seven cases from our medical center were
      identified to involve airbag-related eye injuries. The ages of the patients
      ranged from 4 to 73 years. Ocular injuries included corneal abrasion, corneal
      decompensation, corneal alkali injury, hyphema, iris sphincter tears, vitreous
      hemorrhage, macular retinal pigment epithelium disruption, dislocated posterior
      chamber intraocular lens, and commotio retinae. A review of the medical
      literature showed 74 cases involving 80 eyes. The ages of the patients ranged
      from 2 to 81 years. Males slightly outnumbered females by a ratio of 1.1 to 1.0.
      The speed of the vehicles ranged from 0 to 65 miles per hour, with an average
      reported speed of 31 miles per hour. Reported injuries ranged from mild corneal
      abrasions to open globes. CONCLUSIONS: Ocular morbidity secondary to airbag
      deployment must be recognized as a significant risk for motor vehicle drivers and
      passengers. Improvements in airbag safety will include increased consumer
      awareness and manufacturer design modification.

PMID- 11248821
TI  - Detection of herpes simplex virus and human papilloma virus in ophthalmic
      pterygium.
AB  - PURPOSE: To evaluate the presence of herpes simplex virus (HSV) and human
      papilloma virus (HPV) in pterygia and phenotypically normal conjunctiva and the
      possible relation between viral presence and clinical information. METHODS: Fifty
      pterygia and respective conjunctival specimens were obtained. A personal and
      family history was recorded for each patient. HSV and HPV detection and typing
      were accomplished by polymerase chain reaction amplification of viral sequences.
      Results were statistically analyzed. RESULTS: HSV (type 1) was detected in 11
      (22%), HPV (type 18) in 12 (24%), and both HSV-1 and HPV-18 in 3 (6%) of
      pterygia. No conjunctival specimen displayed HSV, whereas HPV was detected in
      four (8%). Postoperative recurrence and history of conjunctivitis were
      significantly more common in patients with simultaneous detection of HSV and HPV.
      CONCLUSION: The fact that HSV was not detected in conjunctival specimens implies
      a more specific correlation with pterygium, as compared with HPV. The detection
      of potentially oncogenic viruses, such as HSV and HPV, supports the concept that
      pterygium can be considered a neoplastic condition. The correlation of
      postoperative recurrence and a history of conjunctivitis with the simultaneous
      detection of HPV and HSV, implies a possible viral cooperation affecting the
      clinical profile of pterygium.

PMID- 11248822
TI  - Halting pterygium recurrence by postoperative 5-fluorouracil.
AB  - PURPOSE: To investigate the efficacy of postoperative 5-fluorouracil (5-FU) in
      halting recurrence of pterygium. METHODS: Early recurrence of pterygium was
      detected in six eyes of six patients aged 40 to 66 years that, over a 3-year
      period, had undergone pterygium excision in our institution, using the "bare
      sclera" technique. Each of the hyperemic fibrovascular tissues was found to
      override the cornea by 1.5 mm or less in length. Five of these eyes had undergone
      a primary excision and one, a second operation (with intraoperative mitomycin C).
      Upon diagnosis, each eye was treated with two to four injections of 5-FU,
      administered into the dome of the fibrovascular tissue. The dose of 5-FU per
      injection was 1 to 3 mg (mean, 2.1 +/- 0.8 mg). Of all 126 eyes that underwent
      pterygium surgery during that 3-year period, pterygium recurred in nine
      additional eyes but was found to be 2 mm or more in length in each. These eyes
      were not treated by 5-FU. RESULTS: In five of the six treated eyes, the pterygium
      became clinically atrophic and the recurrence process was stopped. No renewal of
      the recurrence process was detected after 12 months or more of follow-up. No
      major complications were related to the use of 5-FU. CONCLUSION: This pilot study
      suggests that when early recurrence of pterygium is already evident, 5-FU
      treatment into the dome of the fibrovascular tissue may be beneficial in halting
      its progression, by rendering it atrophic. A prospective, randomized, controlled
      study is required to confirm the efficacy of this approach.

PMID- 11248823
TI  - Intraoperative daunorubicin to prevent the recurrence of pterygium after
      excision.
AB  - PURPOSE: This study examines the safety, efficacy, and complications of 0.02%
      intraoperative daunorubicin in the prevention of the recurrence of pterygium
      after excision. METHODS: Sixty patients with primary pterygium were included in
      this prospective, randomized clinical study and were randomly divided into two
      groups: the treatment group and the control group. Pterygium was excised under a
      microscope in all patients. The treatment group received intraoperative single
      application of 0.02% daunorubicin for 3 minutes, whereas the control group
      received distilled water for the same duration. Recurrence of pterygium and
      postoperative complications were prime areas of interest. RESULTS: A recurrence
      rate of 6.67% was seen in the treatment group and was 33% in the control group.
      Chemosis of conjunctiva and delayed epithelization were the only complications
      noticed after a mean follow-up of 15 months. CONCLUSION: Initial results indicate
      that a single intraoperative application of 0.02% daunorubicin for 3 minutes
      appears to be a safe and effective adjunct therapy to prevent the recurrence of
      pterygium. However, a much larger cohort study over a considerable number of
      years will eventually demonstrate the safety.

PMID- 11248824
TI  - Bacteriologic and clinical efficacy of ofloxacin 0.3% versus ciprofloxacin 0.3%
      ophthalmic solutions in the treatment of patients with culture-positive bacterial
      keratitis.
AB  - PURPOSE: To compare the efficacy and safety of ofloxacin 0.3% ophthalmic solution
      with ciprofloxacin 0.3% ophthalmic solution in patients with culture-positive
      bacterial keratitis. METHODS: Patients with a microbiologic diagnosis of
      bacterial keratitis were included in this double-masked, parallel-group study and
      were randomized to treatment with either ofloxacin 0.3% or ciprofloxacin 0.3%
      ophthalmic solution. One drop of the study medication was instilled during the
      daytime according to the following schedule: every half-hour on study day 1,
      every hour on days 2 through 4, and every 2 hours on days 5 through 21. Healing,
      the primary outcome measure, was defined as complete reepithelialization,
      accompanied by nonprogression of stromal infiltrate for 2 days. Secondary outcome
      measures included signs and symptoms of infection. Patients were monitored
      throughout the study period for any adverse events. RESULTS: A total of 217
      patients completed the study: 112 were treated with ofloxacin and 105 were
      treated with ciprofloxacin. Streptococcus pneumoniae was the most commonly
      encountered pathogen in all patients. Complete corneal reepithelialization
      occurred in 85% of those treated with ofloxacin and in 77% of those treated with
      ciprofloxacin (p = 0.32). The average time to corneal ulcer healing was 13.7 days
      in those treated with ofloxacin and 14.4 days in those treated with
      ciprofloxacin. Both treatments were well tolerated with no patient discontinuing
      the study because of side effects. CONCLUSION: Ofloxacin 0.3% and ciprofloxacin
      0.3% ophthalmic solutions are effective and safe in the treatment of patients
      with culture-positive bacterial keratitis.

PMID- 11248825
TI  - Topical bactrim versus trimethoprim and sulfonamide against nocardia keratitis.
AB  - PURPOSE: The conventional treatment of Nocardia keratitis is with topical
      sulfonamides. Recently, topical trimethoprim and sulfamethoxazole (Bactrim) has
      been suggested as treatment. This study compares the in vitro efficacy against
      Nocardia asteroides of Bactrim and various ratios of trimethoprim and a
      sulfonamide. METHODS: Antibiotic disks were soaked with various ratios of
      trimethoprim and sulfacetamide sodium. They contained trimethoprim alone,
      sulfacetamide sodium alone, and both trimethoprim and sulfacetamide sodium at
      ratios of 1:40, 1:20, and 1:5. Disks containing Bactrim were also prepared. Each
      disk was placed on blood agar plates streaked with N. asteroides. The plates were
      incubated at 37 degrees C for 72 hours and then examined. RESULTS: Trimethoprim
      alone showed minimal effect. Sulfacetamide sodium alone had a clearance zone of
      12 mm. The plates of trimethoprim and sulfacetamide sodium at ratios of 1:40,
      1:20, and 1:5 had clearance zones of 14 mm, 17 mm, and 27 mm, respectively.
      Bactrim had a clearance zone of 70 mm. CONCLUSION: Trimethoprim or sulfacetamide
      sodium alone is not as effective as both drugs together. As the ratio of the two
      drugs was changed, potency differed against Nocardia organisms. Bactrim was the
      most effective antibiotic against Nocardia organisms. It should be the
      recommended agent for the treatment of Nocardia keratitis.

PMID- 11248826
TI  - Corneal changes of uncertain etiology in mesoendemic onchocercal communities of
      Northern Nigeria.
AB  - BACKGROUND: We report an unusual type of corneal change in some communities
      mesoendemic for onchocerciasis in Kaduna State of Northern Nigeria. METHODS:
      Thirty-four villages with an overall average microfilarial skin snip positivity
      rate of 71% and a total population of about 10,000 were included in a controlled
      trial of ivermectin for onchocerciasis. Detailed slit lamp examination of 806
      persons within this population revealed at least 27 individuals with these
      lesions. There were 11 women and 16 men, aged between 5 and 70 years with a mean
      age of 45 years and a SD of 15 years. Drawings and photographs of 22 of these
      individuals were available for assessment. RESULTS: The lesions were peripheral,
      silvery white, and of two main types: the first group's lesions were flaky,
      refractile, and crystalline in appearance; the second group's lesions were more
      cylindrical in outline and were crisscrossed, giving a lattice-like pattern.
      There were indeterminate forms in between these polar topographies. Of the 25
      subjects who had skin snips performed, 23 were microfilaria-positive. There was
      no accompanying inflammation and the posterior segments showed no evidence of
      crystalline deposits or retinitis pigmentosa, as is found in Bietti's dystrophy.
      The lesions coexisted with typical sclerosing keratitis in six individuals, and
      changes noted in the posterior pole of ten individuals were typical of
      onchocercal chorioretinitis. The evidence for consanguinity was not compelling.
      Differences between and similarities to Bietti's and Schnyder's crystalline
      corneal dystrophy, which are known to be composed of cholesterol crystals, are
      discussed. The lesions are also compared with lattice dystrophy known to be
      composed of amyloid. These lesions may be related to onchocercal infection.
      CONCLUSIONS: We describe some unusual peripheral corneal changes in individuals
      living within areas of Northern Nigeria mesoendemic for onchocerciasis. These
      changes take the form of flaky crystals or lattice within the anterior stroma and
      are common in middle-aged individuals. This may be related to onchocercal
      infection.

PMID- 11248827
TI  - Primary graft failure caused by herpes simplex virus type 1.
AB  - PURPOSE: To present a cluster of four patients with primary graft failure (PGF)
      who consecutively underwent a penetrating keratoplasty (PKP) during a period of
      17 days in one institution. PKP was performed for reasons unrelated to herpes
      simplex infection. Herpes simplex virus type 1 (HSV-1) is presented as the
      possible cause of these PGFs. METHODS: Viral culture of conjunctival swabs and of
      a bandage contact lens was performed on VERO, MRC-5, and Hep-2 cells. The four
      patients underwent subsequent regrafting. Polymerase chain reaction (PCR) for HSV
      1 was carried out on aqueous humor and on a sample of iris and cornea with
      primers. Aqueous humor specimens were pretreated by boiling, and a qiagen
      extraction was performed according to the instructions of the manufacturer on
      biopsies of iris and cornea. Immunohistopathology was performed with polyclonal
      antibodies directed against HSV-1 and -2. RESULTS: Culture of a conjunctival swab
      in three patients and culture of a bandage contact lens in the fourth patient
      were positive for HSV-1. In three of the four patients, PCR was positive for HSV
      1 on aqueous humor and corneal graft tissue. PCR on iris tissue was positive in
      all patients. In three patients, culture for HSV-1 of aqueous humor and of iris
      tissue could not be carried out because of insufficient sample. Viral culture of
      the iris tissue in one patient and of the corneal graft in the four patients were
      negative. Immunohistopathologic examination was positive for HSV-1 in three
      cases. CONCLUSION: These case reports strongly support the hypothesis that HSV-1
      can be the cause of PGF.

PMID- 11248828
TI  - Corneal sensation after topical anesthesia.
AB  - PURPOSE: To compare the topical effects of tetracaine, lidocaine, and bupivacaine
      on corneal sensitivity in normal eyes. METHODS: Corneal touch sensitivity was
      measured with a Cochet-Bonnet anesthesiometer before and at 2.5-minute intervals
      after instillation of the anesthetic agent, until baseline levels had been
      reestablished. Seventeen healthy volunteers were randomized into five groups.
      Group 1 included 0.5% tetracaine (n = 6); group 2, 4% lidocaine (n = 8); group 3,
      0.75% bupivacaine (n = 8); group 4, 0.5% tetracaine + 4% lidocaine (n = 5); and
      group 5, 0.5% tetracaine + 0.75% bupivacaine (n = 7). RESULTS: The duration of
      anesthesia showed no differences between groups 1, 3, and 5. Although there was
      no difference between groups 2 and 4, both groups demonstrated significantly
      longer effects than groups 1, 3, and 5 (p < 0.005). CONCLUSION: The application
      of 4% lidocaine results in a significantly prolonged topical anesthetic effect
      when compared with tetracaine and bupivacaine.

PMID- 11248829
TI  - Congenital corneal anesthesia: a series of four case reports.
AB  - PURPOSE: Discussion of four cases of congenital corneal anesthesia with varied
      systemic associations and modes of presentation. Classification and systemic
      associations of congenital corneal anesthesia along with the importance of multi
      specialty evaluation of such patients. METHODS: Clinical examination of all four
      cases and corneal sensation assessment with Cochet-Bonnet esthesiometer. Thorough
      systemic examination and investigations including serum bio-chemical analysis,
      roentgenography, ultrasonography, nerve conduction studies, and CT scan of the
      patients to identify systemic associations. RESULTS: All four patients proved to
      have bilateral congenital corneal anesthesia with Cochet-Bonnet esthesiometry
      confirming corneal anesthesia. Systemic examination revealed associated
      congenital mesenchymal anomalies in the first case. The second case had
      generalized reduction in pain sensitivity confirmed by nerve conduction studies.
      The third case was an isolated bilateral congenital corneal anesthesia, while the
      fourth was a case of congenital trigeminal nerve anesthesia involving all three
      divisions of both trigeminal nerves. Other causes of corneal anesthesia and self
      inflicted corneal injuries were ruled out by clinical multi-specialty evaluation
      and appropriate investigations. Correct diagnosis and symptomatic treatment aided
      speedy relief of symptoms of all the patients. CONCLUSION: Congenital corneal
      anesthesia is a rare condition and is often a diagnostic dilemma. Although more
      common conditions that cause corneal anesthesia can mislead the clinician, the
      congenital variant should be kept in mind in any case of intractable corneal
      ulceration in children. Early diagnosis, symptomatic treatment and measures to
      prevent further corneal damage will immensely help in retaining useful vision for
      the affected children.

PMID- 11248830
TI  - In vivo and in vitro demonstration of epithelial cell-induced myofibroblast
      differentiation of keratocytes and an inhibitory effect by amniotic membrane.
AB  - PURPOSE: To examine the role of epithelial cells in inducing the differentiation
      of keratocytes into myofibroblasts and to determine whether this effect may be
      inhibited by amniotic membrane matrix. METHODS: In vivo, a 9-mm diameter, partial
      thickness corneal flap was created in 12 rabbit eyes (6 rabbits), which were
      equally subdivided into three groups. The first group was implanted with one
      layer of a 6-mm diameter human amniotic membrane, from which the epithelium had
      been removed by dispase. The second group received an implantation of dispase
      treated amniotic membrane with cultured rabbit corneal epithelial cells. The
      third group received the same implantation as the second group except that the
      cultured corneal epithelial cells were sandwiched between two layers of membrane.
      All corneas were removed 2 weeks later and were subjected to Masson trichrome
      staining and immunofluorescence staining with monoclonal antibodies to alpha
      smooth muscle (alpha-SM) actin for myofibroblasts and cytokeratins for epithelial
      cells. In vitro collagen gels impregnated with different types of human ocular
      surface fibroblasts were seeded with or without rabbit corneal epithelial cells
      before testing for gel contraction. RESULTS: Positive staining of alpha-SM actin
      was noted only in keratocytes adjacent to corneal epithelial cells at the
      incision site and those grown on the basement membrane side of the amniotic
      membrane. Negative staining was noted when epithelial cells were removed by
      dispase or when cultured corneal epithelial cells were sandwiched between two
      layers of membrane. Gel contraction by fibroblasts was significantly promoted
      when epithelial cells were seeded on the gel. In the latter situation, positive
      staining of alpha-SM actin was noted in fibroblasts subjacent to epithelial cells
      but not in those impregnated in the gel. CONCLUSION: Epithelial cells are capable
      of inducing the differentiation of adjacent fibroblasts into myofibroblasts; such
      an induction requires a close epithelial-mesenchymal contact. Amniotic membrane
      alone does not induce this effect and can help block such induction by epithelial
      cells.

PMID- 11248831
TI  - Eurosol versus fetal bovine serum-containing corneal storage medium.
AB  - PURPOSE: To evaluate the usability of Eurosol, a new medium-term corneal storage
      medium without components of bovine origin. METHODS: Ten pairs of human donor
      corneas were placed in tissue culture at 31 degrees C for 7, 14, 21, 28, or 35
      days. One cornea of each pair was cultivated in conventional storage medium on
      Earls' minimum essential medium base containing 2% fetal bovine serum; the other
      one was stored in Eurosol. Corneas were examined with inverse light microscopy;
      corneal thickness was measured; and scanning electron microscopy was performed.
      RESULTS: No significant difference in corneal thickness and endothelial cell
      count was found at any time. Scanning electron microscopy showed a complete
      endothelial cell layer on all corneas. CONCLUSION. The findings indicate a
      potential clinical applicability of the tested serum-free medium-term storage
      medium, offering a safer alternative to conventional media containing fetal
      bovine serum.

PMID- 11248832
TI  - Darkfield biomicrography of eye bank donor corneas.
AB  - PURPOSE: Evaluation of donated corneal tissue for transplantation relies on
      visual inspection by slit lamp biomicroscopy and specular micrography at the eye
      bank and then slit lamp biomicroscopy by the transplanting surgeon. An overall
      grade of tissue quality is assigned, but endpoints for biomicroscopic assessment
      are not universally accepted. We investigated the application of darkfield
      illumination to evaluate corneal transparency and provide a more standardized and
      reproducible method of tissue examination. METHODS: We built a fixture to
      securely hold a standard cornea storage container, and used two versions of
      photographic slit lamp biomicroscopes to examine donated corneal tissue with
      darkfield illumination. RESULTS: In every cornea we examined, darkfield
      illumination portrayed increased subject detail as compared with conventional
      methods of biomicroscopy. The epithelium appeared as a richly textured "ground
      glass" field. We noted variations in transparency that could not be detected with
      conventional slit lamp biomicroscopy. The actual surface area of lesions such as
      cornea verticillata and herpetic dendrites appeared larger in darkfield
      illumination because of its high sensitivity to subtle alterations of
      transparency. CONCLUSION: Darkfield biomicrography of donated corneal tissue
      permits evaluation of the entire surface area, measurement of localized lesions
      of varying brightness, and assessment of epithelial cell coverage. As such, it
      extends our understanding of tissue clarity. Coupled with digital imaging
      technology, darkfield biomicrographs could be shared on the Internet and would
      allow transplanting surgeons to review tissue before selecting it for surgery.
      This technique could also be used in pharmaceutical research to measure changes
      in lesion size after therapy and could be incorporated into an eye bank quality
      assurance program. A new challenge for eye banking is to identify corneas in
      vitro that have undergone refractive surgeries such as laser in situ
      keratomileusis and photorefractive keratectomy-surgical alterations not easily
      seen at the slit lamp. Darkfield biomicrography may also be useful in detecting
      these lesions.

PMID- 11248833
TI  - Superficial keratectomy and conjunctival autograft for Fuchs' superficial
      marginal keratitis.
AB  - PURPOSE: To describe a patient with bilateral, recurrent marginal corneal
      infiltrates consistent with Fuchs' superficial marginal keratitis who developed
      bilateral nasal pseudopterygia encroaching on the visual axis, reducing visual
      acuity in both eyes. METHODS: Bilateral superficial keratectomy combined with
      conjunctival autografting was performed in each eye. RESULTS: Best corrected
      visual acuity improved from 20/60 in the left eye and 20/40 in the right eye to
      20/25 in both eyes. Our patient has had no disease relapses in her right eye, as
      of 29 months after the surgery, but experienced a mild flare-up of marginal
      keratitis in her left eye 8 months after the surgery. Despite this flare-up,
      disease symptoms in the left eye have markedly diminished. CONCLUSION:
      Superficial keratectomy combined with conjunctival autograft is a therapeutic
      alternative in the management of severe, recurrent Fuchs' superficial marginal
      keratitis. In the present case, it has resulted in an improvement in visual
      acuity as well as a decrease in the frequency of disease flare-ups. The clinical
      course of this patient suggests that the conjunctiva may play a role in the
      etiology of Fuchs' superficial marginal keratitis.

PMID- 11248834
TI  - Corneal deposition after high-dose chlorpromazine hydrochloride therapy.
AB  - PURPOSE: To report a case of dermal and ocular changes after prolonged use of
      high-dose chlorpromazine hydrochloride therapy. METHOD: This case report includes
      clinical history, clinical findings, and photographic images of ocular and dermal
      changes. RESULTS. Chlorpromazine therapy in a cumulative dosage exceeding 1,100 g
      resulted in dramatic skin discoloration and multiple crystalline deposits in both
      corneas. Anterior capsular opacities were binocularly present. These changes were
      sufficient to cause reduction in visual acuity. CONCLUSIONS: Chlorpromazine
      deposition at high levels can cause reduction in visual acuity and significant
      skin discoloration.

PMID- 11248835
TI  - 2-Octyl cyanoacrylate medical adhesive in treatment of a corneal perforation.
AB  - PURPOSE: To describe a case of successful treatment of a corneal perforation with
      2-octyl cyanoacrylate. METHODS: 2-Octyl cyanoacrylate was applied at the slit
      lamp with topical proparacaine anesthesia to a cornea with an inferior
      perforation with iris plugging the defect. RESULTS: After application of 2-octyl
      cyanoacrylate, the anterior chamber was noted to deepen, and visual acuity
      improved to 20/200. The glue remained intact for more than 6 weeks and eventually
      fell out. The underlying cornea healed without scarring, vascularization, or
      thinning. CONCLUSION: We have described a case in which 2-octyl cyanoacrylate was
      used to treat a corneal perforation with excellent results. Further study of this
      adhesive will be useful in comparing the effectiveness and safety of 2-octyl
      cyanoacrylate with that of previously studied adhesives.

PMID- 11248836
TI  - Surgical treatment of an intrastromal epithelial corneal cyst.
AB  - PURPOSE: To describe corneal intrastromal epithelial cysts and present a
      minimally invasive surgical technique successfully used to treat such a lesion.
      METHODS: A 5-year-old girl with a progressive, vision-threatening, intrastromal
      corneal opacity in the left eye is described. The patient had a history of
      accommodative esotropia and bilateral medial rectus recession two years before
      presentation. A presumptive diagnosis of an epithelial cyst secondary to
      iatrogenic seeding of the limbal corneal stroma was made. Because of documented
      growth toward the visual axis and a decrease in best-corrected visual acuity,
      surgical treatment was initiated. The cyst was incised and debrided through a 2.0
      mm, partial-thickness, limbus-parallel, clear corneal incision. RESULTS:
      Cytologic analysis of the cyst contents showed intact and degenerated epithelial
      cells, thereby confirming the diagnosis. The cyst walls were scraped through the
      nonenlarged incision, and irrigation resulted in nearly complete clearing of the
      opacity. Stable vision and no recurrences were documented with 21 months of
      follow-up. CONCLUSION: This minimally invasive surgical approach may be a good
      alternative to previously described treatments for intrastromal corneal cysts.

PMID- 11248837
TI  - Candidal endophthalmitis after keratoplasty.
AB  - PURPOSE: To report a case of explosive fungal endophthalmitis after penetrating
      keratoplasty and to review additional published and unpublished cases to consider
      possible strategies for prevention. METHODS: Records of this patient with
      postkeratoplasty candidal endophthalmitis and previously reported cases of
      postkeratoplasty candidal endophthalmitis were reviewed. Additional information
      of 26 unpublished cases was obtained from the Eye Bank Association of America.
      RESULTS: After standard keratoplasty, the patient developed precipitous
      endophthalmitis on the second postoperative day. Abundant contamination with
      Candida was found in the residual donor corneoscleral rim, and Candida albicans
      was isolated from the aqueous humor of the recipient. Despite therapy with local
      antimicrobial agents, intraocular amphotericin B, and systemic fluconazole, the
      patient had a poor outcome with hand-motion visual acuity. Of the 44 collected
      cases of postkeratoplasty candidal endophthalmitis, 40 (91%) had the same
      organism cultured from the donor rim or medium. Forty-three donor corneas had
      been preserved in cold storage medium at 4 degrees C. Of 15 cases in which the
      outcome was available, 9 (60%) resulted in visual acuity of 20/200 or worse.
      CONCLUSION: Case reports confirm the occurrence of donor-to-host transmission of
      postkeratoplasty candidal endophthalmitis. Despite the low reported incidence,
      the poor prognosis of the affected eye in the  ajority of these cases suggests
      the need for antifungal supplementation of cold preservation media and other
      preventative strategies.

PMID- 11248838
TI  - Use of human fibrin glue and amniotic membrane transplant in corneal perforation.
AB  - PURPOSE: To repair corneal perforation using human fibrin glue (HFG) and amniotic
      membrane transplant (AMT). METHODS: Three patients in whom central corneal
      perforations, approximately 2 mm in diameter, occurred after ocular or systemic
      disease were successfully cured using HFG and AMT. The technique consists first
      of using a high-viscosity sodium hyaluronate viscoelastic material to restore
      anterior chamber depth followed by a debridement of the ulcer. The perforation
      site is filled with the HFG to corneal surface level. The so-formed plug is then
      secured with an AMT to avoid its extrusion. An extended-wear bandage contact lens
      and topical antibiotics were used in these patients for 3 weeks. RESULTS: Total
      reepithelialization was observed after an average of 15 postoperative days. The
      AMT dissolved within 8 weeks to uncover a whitish scar formed within the
      perforation sites. No complications were observed in any patients. After a follow
      up period of 195-325 days, all corneas remained stable; there was no infection or
      ulcer recurrence, but some corneal scar thinning was observed in all three cases.
      CONCLUSION: The described surgical approach using HFG and AMT allowed a
      successful repair of corneal perforations with a diameter of 2 mm associated with
      significant loss of stroma. This method may be a good alternative to delay
      penetrating keratoplasty for treating corneal perforations, especially in acute
      cases in which graft rejection risk is high. eal

PMID- 11248839
TI  - Histopathologic findings of cornea verticillata in a woman heterozygous for
      Fabry's disease.
AB  - PURPOSE: To report the histopathologic findings of the cornea verticillata
      observed in a woman who was heterozygous for Fabry's disease. METHOD: A 67-year
      old woman was found to have a whorl-like corneal opacity on her visit to the
      Department of Ophthalmology. Aichi Saiseikai Hospital. Her visit was because of a
      sudden loss of vision in her right eye owing to a central retinal artery
      occlusion in association with an ophthalmic artery occlusion. The patient died
      suddenly of an acute heart failure; with family consent, an autopsy was performed
      and the right eye was removed for histopathologic examination by light and
      electron microscopy. RESULTS: Low levels of alpha-galactosidase in the leukocytes
      together with the corneal finding led to the diagnosis of heterozygous Fabry's
      disease. Light microscopy revealed a 0.3- to 0.5-microm thick layer between the
      epithelial and Bowman's layers. Oil red O positive deposits were accumulated in
      the subepithelial layer, and the density varied in different regions. Electron
      microscopy showed that subepithelial layer differed in thickness, and the basal
      lamina reduplicated regionally. We were not able to determine the structure that
      correlated with the "ridge" in the central part of the cornea. CONCLUSION: The
      oil red O positive deposits and their variation in density in the subepithelial
      area of the cornea may have caused the characteristic whorl-like corneal opacity
      in this woman who was heterozygous for Fabry's disease.

PMID- 11248840
TI  - Two cases of bilateral, stromal ring opacity of the cornea.

PMID- 11248842
TI  - [Innovative cell culture methods in drug development].
AB  - The animal studies necessary for drug registration are time-consuming, costly,
      and often stressful for the animals. Toxicological screening of drug candidates
      early in development with in vitro cell culture systems is therefore of
      relevance. In contrast to animal studies, in vitro cell culture methods are
      characterized by a low compound requirement and a short duration. Additionally it
      is possible to include mechanistic studies or to test for toxicity specific to
      humans. Therefore, early toxicological screening can provide a useful support for
      selecting the most promising drug candidate. Primary hepatocytes can be used to
      measure the cytotoxicity of a test compound. These results can be used to
      estimate general toxicity. Measuring endpoints like apoptosis, redox status, or
      gene expression profiles can help to answer mechanistic questions. The use of
      primary human hepatocytes provides early predictivity for hepatotoxicity specific
      to humans. Since teratogenic findings in animal studies often lead to abandonment
      of development, it is reasonable to use an in vitro embryotoxicity assay for
      early determination of the teratogenic potential of a compound, e.g. the
      embryonic stem cell test (EST) which was recently developed by ZEBET. In the EST
      embryonic stem cells are investigated for their preserved capability to
      differentiate into cardiomyocytes following drug exposure. In comparison
      cytotoxicity of the test substance is analyzed in embryonic stem cells and in
      differentiated fibroblast cells. In a validation study initiated by ECVAM the EST
      shows a high correlation with in vivo data.

PMID- 11248841
TI  - The adverse neuro-developmental effects of postnatal steroids in the preterm
      infant: a systematic review of RCTs.
AB  - BACKGROUND: Recent reports have raised concerns that postnatal steroids may cause
      neuro-developmental impairment in preterm infants. This systematic review was
      performed with the objective of determining whether glucocorticoid therapy, to
      prevent or treat bronchopulmonary dysplasia, impairs neuro-developmental outcomes
      in preterm infants. METHOD: A systematic review of the literature was performed.
      Medline was searched and articles retrieved using predefined criteria. Data from
      randomized controlled trials with adequate neuro-developmental follow up (to at
      least one year) were entered into a meta-analysis to determine the effects of
      postnatal treatment of preterm infants with glucocorticoids. Cerebral palsy
      rates, and neuro-developmental impairment (developmental score more than 2SD
      below the mean, or cerebral palsy or blindness) were analyzed. The studies were
      divided into 2 groups according to the extent of contamination of the results by
      treatment of controls with steroids after the initial study period, those with
      less than 30% contamination, and those with more than 30% contamination or size
      of contamination not reported. RESULTS: Postnatal steroid therapy is associated
      with an increase in cerebral palsy and neuro-developmental impairment. The
      studies with less contamination show a greater effect of the steroids, consistent
      with a real direct toxic effect of steroids on the developing central nervous
      system. The typical relative risk for the development of cerebral palsy derived
      from studies with less than 30% contamination is 2.86 (95% CI 1.95, 4.19). The
      typical relative risk for the development of neuro-developmental disability among
      followed up infants from studies with less than 30% contamination is 1.66 (95% CI
      1.26, 2.19). From this subgroup of studies, the number of premature infants who
      need to be treated to have one more infant with cerebral palsy (number needed to
      harm, NNH) is 7; to have one more infant with neuro-developmental impairment the
      NNH is 11. CONCLUSIONS: Postnatal pharmacologic steroid treatment for prevention
      or treatment of bronchopulmonary dysplasia is associated with dramatic increases
      in neuro-developmental impairment. As there is no clear evidence in the
      literature of long term benefit, their use for this indication should be
      abandoned.

PMID- 11248843
TI  - [Modern drug development by molecular- and cell-biological methods].
AB  - V79 cells have been genetically modified for metabolism functions of humans in
      drug metabolism and metabolic activation of chemicals. All V79 constructs
      together form the V79 Cell Battery by which GenPharmTox BioTech AG, Tutzing,
      Germany, is capable of checking drug metabolism early on during preclinical drug
      development with immediate relevance for the clinical testing of drugs. It is
      impossible to obtain those data from animal testing. Therefore, the intrinsic
      problems in extrapolating data generated from animal testing to humans has been
      circumvented.

PMID- 11248844
TI  - [Recent developments on the European ban on animal experiments for cosmetics].
AB  - For the second time the European Commission has postponed the sales ban on
      cosmetics products that have been developed and tested in animal experiments now
      until 2002. In the meantime the Commission wants to adopt the Seventh Amendment
      of the EU Cosmetics Directive. In its draft the Commission proposes to scrap the
      sales ban and replace it with an animal testing ban. This change would avoid
      possible conflicts with the WTO, however, from the animal welfare point of view
      would result in animal testing moving into third countries instead of avoiding
      them. This is because cosmetics products tested on animals outside the EU could
      be sold in the EU without any restrictions. As a consequence this measure would
      take the pressure from authorities and industry to further develop and adopt
      alternative methods. Other proposed measures are not acceptable from the animal
      welfare point of view, e.g. because they contradict Directive 86/609 and would
      result in a delay of the application of validated alternative methods. The
      Deutscher Tierschutzbund therefore still demands an immediate and complete sales
      ban in connection with an animal testing ban within the EU.

PMID- 11248845
TI  - [Development of alternative methods by the EDQM and the Biological
      Standardization Program].
AB  - Due to the complexity of their composition and mode of action and because of the
      absence of adequate alternative methods the quality control of biologicals (e.g.
      vaccines, sera) continues to be performed to a large extent in animal
      experiments. In most cases, the properties of the compounds are compared to those
      of a reference preparation. For Europe, the specifications for the biologicals
      are listed in the European Pharmacopoeia, which is published by the European
      Directorate for the Quality of Medicines (EDQM) in Strasbourg, on behalf of the
      member states. The EDQM is also in charge of the organisation of the Biological
      Standardisation Programme and the network of the national control laboratories
      (Official Medicines Control Laboratories, OMCL). The Biological Standardisation
      Programme pursues the goal to establish common European reference preparations
      and to standardise the methods used for the quality control of biologicals with
      the explicit goal to develop alternative methods whenever possible. This survey
      describes how the EDQM via the European Pharmacopoeia, the Biological
      Standardisation Programme and the OMCL network, supports the 3R concept and shows
      examples of its successful application.

PMID- 11248846
TI  - ["Replacement Methods to Animal Testing" as the incentive topic of the German
      Ministry of Education and Research. Selected results on biological drugs].
AB  - Since 1980, BMBF, in co-operation with the appointed project representative BEO
      (Biology, Energy, Environment), supports research projects with the central goal
      of the reduction of animal testing. Beginning with the announcement about
      promoting "Projects in Replacement Methods to Animal Testing" in 1984, a separate
      incentive topic of research was fostered within the framework of the
      biotechnological program of the German Federal Government. It is being updated
      continuously by current reports. The BMBF incentive topic represents the largest
      and longest running support activity in the field world-wide. During a time-span
      of 20 years, about 14 million German Marks (approx. 7 millions per annum) were
      provided, supporting about 230 projects. To date, all applications judged
      favourably in regard to contributing to potential and substantial savings could
      also be funded. The incentive topic is being realised in accordance with the 3R
      principle, following Russel and Burch. Primary attention is given to tests with
      high levels of stress or involving large numbers of animals. At present, special
      attention is given to the development and validation of alternatives to animal
      testing which are required by law. Emphasis is also put on joint projects by
      testing and regulation authorities together with industrial users in order to
      broaden the application of these methods and to aid in accelerating the amendment
      of respective legal regulations. The BMBF continues to adhere to the objectives
      of the emphasised support and will furnish funding at the present level in the
      future. Also, together with representatives of testing- and regulating
      authorities, of industry, science, respective federal authorities and animal
      protection, the BMBF has developed a new concept to expand funded activities in
      the future to include animal testing in basic research in a target-fashioned
      structure. This will be published shortly through a new public announcement. As a
      complement to the present application procedure ("bottom-up-principle"), new
      research approaches are being prepared within a limited scope regarding
      particularly relevant topics (i.e. transgenic animal models) as a "top-down
      principle" by means of workshops and accompanying studies. Additionally, reports
      are appearing concerning the results of selected projects supported by the
      emphasised support of the BMBF for "Biologica", particularly regarding the
      realisation of results in the practical reduction of animal testing. The BMBF is
      supporting a total of 27 projects with respect to "Biologica". Central to the
      majority of these projects (21) is the test of vaccines, and there in particular,
      the potency test of particular vaccines. Using four examples, it is being
      demonstrated that the practical translation of the results of projects always
      requires the co-operation of the respective partners, and that the complete
      application of suitable replacement methods usually becomes possible only after
      the conclusion of a phase of development and testing of several years.

PMID- 11248847
TI  - [100 years of erysipelas prophylaxis: significance and reduction of animal
      experiments].
AB  - The history of erysipelas prophylaxis began in 1882 when Pasteur first discovered
      the attenuating effect of rabbit passages on the erysipelas bacterium. Ten years
      later, the German veterinarian Lorenz demonstrated the protecting effect of
      erysipelas antiserum. He developed a method of serovaccination which was
      successfully used in Germany for more than 50 years. Both scientists employed
      laboratory animals for the development of their live vaccines. Lorenz
      additionally recommended an animal model with grey mice to control the potency of
      erysipelas sera. In 1944, Fortner and Dinter published the results of their
      investigation on a skin scarification test in swine. This modus of infection was
      the basis of the first reliable model for efficacy testing of erysipelas vaccines
      in domestic animals. Shortly after World War II, the first inactivated erysipelas
      vaccines were being developed. At that time, also a strict quality control was
      introduced for this product group which required extensive animal experiments in
      laboratory mice and pigs for the determination of efficacy. WHO established
      International Standards for erysipelas vaccines and antisera concerning potency
      testing in mice. These animal models were finally incorporated in pharmacopoeia
      monographs. Animal experiments have played an important role in the development
      and quality control of erysipelas vaccines. And the success of this quality
      control based on animal experiments has had a significant impact on the quality
      control systems for veterinary vaccines in general. Today, we have a far more
      detailed knowledge about pathogenesis and immunology of swine erysipelas. This
      knowledge now allows the introduction of alternative methods according to the 3R
      concept. With these new methods, animal numbers can be decreased and suffering
      caused by challenge infection can be reduced. The ultimate goal, i.e. quality
      control of erysipelas vaccines carried out without routine performance of animal
      experiments, should be achieved in the near future.

PMID- 11248848
TI  - [Development of in vitro methods for the potency testing of clostridial
      vaccines].
AB  - Cell culture assays, using the MDCK cell line was confirmed as being sensitive to
      the C. perfringens epsilon toxin and VERO cell line to the C. novyi type B alpha
      toxin. Cell culture assays using these cells were developed and the test
      conditions were standardised. The antitoxin titres of rabbit antisera were
      calculated and compared with those of the manufacturers. The correlation
      coefficients between in vitro and in vivo method were calculated and were
      significant. The cell culture assay offers a valid in vitro alternative to the
      animal experiments for the titration of sera generated in the course of potency
      tests of clostridial vaccines.

PMID- 11248849
TI  - [Clinical endpoints during rabies vaccine control tests].
AB  - All warm-blooded animals, including humans, are susceptible to rabies. The
      infection with the virus leads inevitably to the death of the recipient. Vaccines
      and anti-serums are at present the only possibility to prevent rabies infections
      in the human and veterinary medicine. In order to be able to guarantee the
      production of a reliably safe and effective vaccine, each batch has to be tested.
      These tests contain animal experiments. Alone for efficacy tests of rabies
      vaccines done for each batch far over one hundred mice are used. In a defined
      time period in challenge experiments the number of deaths rates of immunised
      animals are compared with non vaccinated control animals. At present several
      replacement methods for this test are in development. However, so far none of
      them has been validated in an international multicenter study. The modifications
      necessary for example in the WHO (World Health Organization) or O.I.E. (Office
      International d"Epizooties) guidelines will need several more years. Therefore,
      this test method will be internationally used in the foreseeable future. In order
      to avoid unnecessary suffering of the animals, we looked for signs, which can be
      used to replace lethality as criterion. For this purpose score-sheets were
      developed, on which the observed clinical signs were recorded. The decrease of
      body-temperature, which was measured with transplanted transponders, occurred too
      late to be usable. A clear reduction of the body weight is the earliest sign of
      an illness. Slow and circular movements, followed by cramps and paralyses, are
      the first neurological symptoms of rabies. The combination of these parameters
      can serve as a reliable indicator for humane endpoints. This saves the mice on
      average between four and five days of the most stressful phase of the experiment
      and is a clear "refinement" of the test conditions in the sense of the 3R. A
      video which shows the clinical signs is available.

PMID- 11248850
TI  - [A new application for the human whole blood test: development of an assay to
      assess the health risk of air-borne microbial contaminations].
AB  - The pathogenic properties of environmental microorganisms as well as pyrogens as
      fragments of those bacteria (especially endotoxins) for humans is increasingly
      recognised. Various clinical syndromes are described after contact with airborne
      microbial contaminants via the respiratory tract: Sick-building-syndrome,
      humidifier lung (a form of hypersensitive pneumonitis), "Monday sickness" etc.
      Air-conditioning and ventilation systems intensify this problem as well as
      storage of compost within the household which represents a considerable source of
      airborne pollutants. In 1995 a new method for the detection of pyrogenic (fever
      inducing) hazardous substances was described by Hartung and Wendel. This whole
      blood assay utilises the natural reaction of the immune system in order to detect
      a broad spectrum of pyrogens very sensitively in the relevant species. Injectable
      drugs are the main area of application in which this innovative test has already
      proven effective and is currently validated for inclusion into European
      Pharmacopoeia. In co-operation with the FU Berlin we could demonstrate in
      ventilation systems in animal stables that the whole blood pyrogen test can also
      detect airborne environmental microorganisms very sensitively. The filtration
      technique for collection of these germs is an established method for air
      conditioning and ventilation systems. In co-operation with the FU Berlin
      (Institut fur Tier-und Umwelthygiene) and the filter producer Sartorius this
      method is currently developed for the detection of airborne contaminations.

PMID- 11248851
TI  - [Effect of the preservative thiomersal on the release of interleukin-1 beta from
      human peripheral blood cells].
AB  - Several vaccines have been tested in the human whole blood pyrogen test as an
      alternative to the rabbit pyrogen test. As reported previously by our group, the
      alternative test system is basically applicable to vaccines. The widely used
      conservative thiomersal is influencing the test system. Surprisingly, the
      induction of fever inducing cytokines by endotoxin contaminations and other
      pyrogens can be suppressed by thiomersal.

PMID- 11248852
TI  - [Development of a novel influenza vaccine derived from a continuous cell line].
AB  - Influenza viruses for production are presently produced in embryonated hen"s
      eggs. This conventional standard methodology is extremely cumbersome; it requires
      millions of eggs and an extensive purification to reduce the amount of
      contaminating egg proteins and to minimise the risk of allergies against egg
      albumin. The shortage of eggs in a pandemic situation, the selection of egg
      adapted variants and the presence of adventitious viruses has emphasised the
      necessity for production of Influenza vaccines on a well characterised stable
      cell line. Our established serum and protein free Vero cell technology has been
      successfully adapted to large scale production of a huge variety of Influenza
      virus strains. The production in 1200 liter fermenter cultures under serum free
      conditions gave antigen yields comparable to the conventional embryonated egg
      technology. The development of a rapid and efficient purification scheme resulted
      in a safe high purity vaccine which was at least as immunogenic as conventional
      egg-derived vaccines in a mouse model. Clinical trials in the UK, Poland and
      Austria demonstrated that the Vero cell derived influenza vaccine is well
      tolerated, safe and highly immunogenic in humans.

PMID- 11248853
TI  - [Mediator release assay of rat basophil leukemia cells as alternative for passive
      cutaneous anaphylaxis testing (PCA) in laboratory animals].
AB  - Passive cutaneous anaphylaxis (PCA) is an animal model for inflammatory reactions
      in Type I allergy. An in vitro assay based on IgE dependent and allergen-induced
      mediator release of RBL-2H3 cells is presented as an alternative for PCA. The
      assay has been adopted to the special needs of examining allergen extracts and
      has been proven to be practicable and reliable. A high number of samples can be
      processed quickly in one assay, with intra-assay variations below 10%. The first
      successful applications are the measurement of biologic potencies in allergenic
      extracts and the determination of murine serum IgE antibodies. Further studies
      will show whether this assay is suited to evaluate the efficiency of anti
      inflammatory and anti-allergic drugs.

PMID- 11248855
TI  - [Good cell culture practice (GCCP)--an initiative for standardization and quality
      control of in vitro studies. The establishment of an ECVAM Task Force on GCCP].
AB  - Cultured human and animal cells are increasingly used as the basis for
      simplified, direct test systems that have the potential to be more controllable
      and more reproducible than in vivo test systems. However, if a biological test
      system is simplified to fundamental levels then it is paramount that the
      essential components of such a reduced systems are closely defined and
      reproducible. Thus, minimal requirements for quality standards in cell and tissue
      culture have to be defined. It is the aim of this GCCP initiative to establish
      principles for standardisation, rationalisation, and international harmonisation
      of cell and tissue culture laboratory practices. Therefore, in analogy to Good
      Laboratory Practice (GLP), a Good Cell Culture Practice (GCCP) was initiated at
      the 3rd World Congress on Alternatives and Animal Use in the Life Sciences,
      Bologna, 29. August-2. September 1999. This "Bologna Statement on Good Cell
      Culture Practice" was presented, discussed, and refined in a Workshop, and a
      final version was approved at the closing ceremony of the Congress by the
      scientific audience. Based on the Bologna Statement, an ECVAM Task Force on GCCP
      was initiated, that is chaired by Thomas Hartung and Sandra Ceocke, in which
      experts in the field should elaborate minimal requirements for quality standards
      in cell culture. It is the intention of the GCCP Guidelines to encourage
      consensus among all concerned with the use of in vitro systems, in order to
      establish and maintain best laboratory practices, to promote effective quality
      control systems, to facilitate education and training, to support journal
      editors, and to help any authorities who need to interpret and apply conclusions
      based on in vitro data.

PMID- 11248854
TI  - [In vitro models of intestinal and alveolar epithelium cultures in pharmaceutical
      research].
AB  - The progress of modern bio- and information-technology has made an enormous
      impact on the development of new drugs: At the one hand, computer-aided drug
      design and automated high-throughput screening has enormously facilitated the
      chemical synthesis of new drug candidates. At the other hand, the number of
      macromolecular biopharmaceuticals, such as peptides, proteins, antisense agents
      or gene vectors is continuously increasing. Whether or not such new entities can
      indeed be developed to safe and efficient medicines, is largely determined by the
      question, if these molecules are able to reach their actual target (receptor)
      within the patient"s body. Often, biological barriers, such as the mucosal
      epithelium of the gastrointestinal tract cannot be passed. In vitro test systems
      based on human epithelial cells may help to determine those candidate drugs which
      are well absorbed after oral application. Moreover, such cell culture models are
      helpful tools for the discovery for new delivery routes for those molecules,
      which cannot be administered by oral application. In this context, there is an
      increasing interest in the pulmonary delivery of drugs, as well as in the
      development of cell culture systems to model the blood-air barrier represented by
      the alveolar epithelium.

PMID- 11248856
TI  - [The importance of standardised cell culture methods for the routine toxicology
      in pharmaceutical companies].
AB  - The establishment and the use of standardised cell cultures build the basis for
      toxicological investigations and guarantees the comparison over years. The
      requirement for these investigations in vitro are mainly primary cell cultures
      from the target organs. The cell cultures should keep, also under long term
      culture conditions, the organ differentiation. This will be supported by new
      developments in the fields of cell culture media, supplements and coating
      material of the cell culture dishes. Routinely, cells from toxicologically
      important organs like liver, kidney and nervous system were used in vitro.
      However, mechanistic investigations of toxicological findings in vivo made the
      use of cell systems from other organs like cartilage, bone, skeletal and heart
      muscle cells, testis eg necessary. All cell culture systems were established and
      standardised to allow repeated tests under the same conditions. The determination
      of characteristic proteins or enzymes of the related organ will demonstrate the
      organ like quality of the cell cultures. The central question of toxicology is
      the risk assessment. Here, the in vitro toxicology will provide important
      information by a comparison between human and animal cell cultures under the same
      conditions.

PMID- 11248857
TI  - [In vitro permeability studies as a substitute for in vivo studies--which
      requirements have to be met?].
AB  - In order to reduce costs and shorten time-to-market, the permeability of drug
      substances can be characterized by in vitro techniques including the use of cell
      and tissue models. It is required to apply appropriate quality standards similar
      to those used in animal or clinical studies. The Caco-2 cell model is a well
      established and recognized in vitro technique in research, industry and in the
      drug discovery sector. However, the lack of standardized operating is reflected
      in the heterogeneity of the data acquired using this model. Using the Caco-2 cell
      model as an example, this paper demonstrates how to test the suitability of a
      cell culture model for conducting drug permeability studies. The procedures
      involve not only the characterization of cell morphology but also functional
      assessment of the model and the periodic testing of monolayer permeability. Both
      the useful comparison of permeability data and the reliable prediction of in vivo
      permeability require prior classification of the in vitro permeability in
      accordance with the FDA"s Biopharmaceutics Classification System (BCS).

PMID- 11248859
TI  - The aging face and skin: common signs and treatment.

PMID- 11248858
TI  - Michael W. Fallon Jr.

PMID- 11248860
TI  - Soft-tissue augmentation with Fascian.
AB  - For a century, under various implant circumstances, the propensity of pFGs to be
      replaced with host fibroblasts and collagen has been established. Harvested from
      screened human donors, Fascian is an injectable formulation of the same substance
      that is applicable for soft-tissue repair and augmentation. Provided in preloaded
      syringes, the material has many advantages over presently available substitutes.
      This freeze-dried material does not require refrigeration, and, because of low
      allergenicity, test implantation is not indicated. Because it is available in
      multiple particle sizes that can even pass through a 27-gauge needle, Fascian is
      suitable for fine defects, and because of the material's volume and density,
      lesions usually not considered for injectable augmentation may be treated with
      larger particles. The process of tissue particulation has not altered the
      inherent graft properties, and Fascian seems to evoke the same process of
      collagen replacement that routinely occurs in larger grafts.

PMID- 11248861
TI  - Structural fat grafts: the ideal filler?
AB  - In the search for injectable subcutaneous fillers, fat harvested, transferred,
      and placed in the manner previously described has most of the characteristics of
      an ideal filler. It is biocompatible, versatile, stable, long-lasting, and
      natural-appearing. The key to successful fat grafting lies in the technique.
      Harvesting, refinement, and transfer of subcutaneous tissue to provide pure,
      intact parcels of fat are essential for successful fat grafting. The surgeon also
      must infiltrate the refined fat parcels into the recipient site so that they
      survive predictably and uniformly, become integrated into the host tissues, and
      accomplish the desired structural alteration. The key to attaining these goals is
      the placement of minuscule amounts of fatty tissue with each withdrawal of the
      infiltrating cannula. This maneuver maximizes the surface area of contact between
      the newly transplanted tissues and the recipient tissues. Applying this technique
      to enact structural volume alteration of the face can result in subtle or
      striking improvements in the appearance of patients. The ideal substance for soft
      tissue augmentation still eludes physicians, but fat grafting through a blunt
      cannula seems to be the safest of all of the fillers used; in the hands of an
      experienced surgeon, it can provide long-lasting, natural-appearing structural
      changes.

PMID- 11248862
TI  - Hyaluronic acid for soft-tissue augmentation.

PMID- 11248863
TI  - Primary and adjunctive use of botulinum toxin type A (Botox) in facial aesthetic
      surgery: beyond the glabella.
AB  - The use of Botox for the treatment of hyperkinetic facial lines and furrows is
      another effective primary, adjunctive, or prophylactic therapy to offer cosmetic
      patients in the spectrum of treatment options for full facial rejuvenation.
      Unwanted side effects can be minimized, and beneficial effects can be maximized
      with a thorough understanding of the facial soft-tissue anatomy, proper patient
      selection, and administration of the lowest effective doses with minimal volume
      of delivery. Most often, Botox injection does not replace surgery, skin
      resurfacing, soft-tissue augmentation, or skin care; however, it is useful when
      used alone or with the various treatment options to give selected patients the
      most effective and comprehensive solutions for a more youthful appearance.

PMID- 11248865
TI  - Nonsurgical (nonscalpel) facial rejuvenation: 100 pearls.

PMID- 11248864
TI  - Modified phenol chemical face peels: recognizing the role of application
      technique.
AB  - To determine the relative roles of phenol concentration, croton oil
      concentration, and application techniques, the authors obtained three additional
      human biopsy studies. The last study was a randomized, controlled, prospective
      study with surgeon, pathologist, and third-party evaluators blinded during the
      application process and during the gross and histologic evaluations. Conclusions
      drawn from the findings of the studies included the following: Rubbing more coats
      of phenol, with or without croton oil, produces more inflammation and fibrosis.
      Adding croton oil reduces the threshold of injury from 20 to 50 coats to 5 to 20
      coats applied with a cotton tip applicator, confirming the clinical impression
      that croton oil resin facilitates injury pattern of wounding when used with
      phenol in 35% to 88% concentrations. 48% phenol without croton oil can provide
      the same long-term results as 48% phenol with croton oil. The data suggest that
      the application technique is more important than the concentration of phenol or
      croton oil alone.

PMID- 11248866
TI  - Overview of complications of nonsurgical facial rejuvenation procedures.
AB  - An in-depth understanding of potential adverse sequelae related to aesthetic
      facial rejuvenation and available management modalities, should such a
      complication occur, enables the aesthetic surgeon to reduce his or her
      complication profile and also minimize the results of such adverse sequelae,
      eventuating improved patient care and satisfaction.

PMID- 11248867
TI  - The role of ancillary personnel and skin care.
AB  - It is the primary responsibility of the plastic surgical skin care specialist to
      support the patient care philosophies of the plastic surgeon and the practice,
      while contributing his or her expertise to optimize patient care outcomes. The
      clinical role in the medical environment differs from other sources for skin care
      because of the patient care component; the whole person enveloped in the skin is
      included in the equation. The addition of nurses and aestheticians in this
      complementary role to the practice speaks to the new paradigm of patient care,
      for they markedly contribute to the well-being of the patient. Quality skin care
      programs affect the final results of nonoperative techniques for facial
      rejuvenation. Plastic surgical skin care specialists recognize the uniqueness of
      their roles. They willingly demonstrate their passion for skin care excellence,
      while participating as the newest member on the plastic surgical team.

PMID- 11248868
TI  - An overview of cutaneous laser resurfacing.

PMID- 11248870
TI  - Facial soft-tissue augmentation with allogeneic human tissue collagen matrix
      (Dermalogen and Dermaplant).
AB  - Soft-tissue augmentation lends another dimension to facial rejuvenation. Human
      collagen tissue matrix offers the most physiologic solution to dermal volume
      depletion, structural soft-tissue malposition, and the correction of facial
      rhytides and various soft-tissue contour defects. Results with the use of
      Dermalogen have been comparable with other injectable dermal agents with the most
      natural effects. The absolute longevity or persistence of human tissue collagen
      matrix has not been established fully and depends on facial region, technique,
      and total volume administered. The natural fate of most related bio-materials
      suggest that internal dosing is required to maintain maximum effects. Dermaplant
      is now commercially available and is an effective agent for facial soft-tissue
      augmentation-nasolabial folds and lip augmentation-and secondary eyelid and nasal
      reconstruction. Final clinical studies will provide data on long-term persistence
      and relative results when compared with other acellular dermal and alloplastic
      grafts.

PMID- 11248869
TI  - Collagen substitutes: bovine collagen.
AB  - Injectable collagens (e.g., ZC-I, ZC-II, ZP) provide the physician with a manner
      for approaching mild contour defects. They are a temporary, biocompatible
      solution to many, but certainly not all, soft-tissue deficiencies. The adverse
      reaction profile is of an acceptably low level and indeed only of local
      significance. For the physician and patient to benefit from these agents,
      however, effective, reproducible implantation techniques must be developed by the
      treating physician. As the physician's experience with these agents increases, so
      will his or her ability to produce aesthetically pleasing results.

PMID- 11248871
TI  - Alloderm acellular dermal graft: applications in aesthetic soft-tissue
      augmentation.
AB  - The advantages of Alloderm outweigh its disadvantages. This material provides a
      natural alternative to alloplastic materials in certain situations. Alloderm
      integrates into the patient's tissue, eliminating concerns associated with
      alloplastic material. Because it is of human origin, there is a remarkable lack
      of tissue reactivity after implantation. Volume persistence remains a concern.
      Because reports vary, the surgeon must determine the degree of persistence in his
      or her own hands and use larger pieces or multiple layers if necessary.
      Currently, Alloderm acellular human dermal tissue seems to be a successful
      modality for soft-tissue augmentation to improve various aesthetic and
      reconstructive deficiencies.

PMID- 11248872
TI  - Iron deficiency in developed countries: prevalence, influence of lifestyle
      factors and hazards of prevention.
AB  - OBJECTIVE: To review the prevalence of iron deficiency in developed countries,
      the influence of lifestyle factors that may contribute to its occurrence, and
      dangers of population directed prevention. DESIGN: Relevant literature was
      selected to identify populations at risk for iron deficiency and iron overload.
      RESULTS: Although iron deficiency anaemia is not a major health problem in
      developed countries, specific groups of the population remain endangered. These
      groups are young children, adolescents, pregnant women, the elderly, blood
      donors, vegetarians, endurance athletes and migrants. On the other hand, about
      10% of Caucasians carry the mutation for hereditary haemochromatosis and are at
      risk for iron overload. CONCLUSION: Measures to prevent iron deficiency should be
      specifically aimed at population groups at risk. Actions to increase iron intake
      and bioavailability in the general population can be harmful for subjects with
      homozygous and heterozygous forms of iron overload diseases.

PMID- 11248873
TI  - Comparison of body composition methods: a literature analysis.
AB  - OBJECTIVE: To examine the comparability of different methods to assess percentage
      body fat (BF%) against underwater weighing (UWW). DESIGN: A meta-analysis on 54
      papers, published in 1985-96, on healthy, adult Caucasians. METHODS: The mean BF%
      from different studies were treated as single data points. In addition to UWW,
      the studies included one or more of the following methods: 3- or 4-component
      model, dual-energy X-ray absorptiometry (DXA), dual-energy photon absorptiometry,
      isotope dilution, bioimpedance (BIA), skinfolds or near-infrared interactance
      (NIR). Within each of the methods, the analyses were done separately for
      different mathematical functions, techniques or instruments. MAIN OUTCOME
      MEASURES: Bias (mean difference) and error (s.d. of difference) between BF%
      measured by UWW and the other methods. RESULTS: The 4-component model gave 0.6
      (95% confidence interval for the mean, CI: 0.1 to 1.2) BF% higher results than
      UWW. Also the 3-component model with body density and total body water (+1.4 BF%,
      95% CI: +0.3 to +2.6), deuterium dilution (+1.5 BF%, 95% CI: +0.7 to +2.3), DXA
      by Norland (+7.2 BF%, 95% CI: 2.6 to 11.8) and BIA by Lukaski et al. (+2.0 BF%,
      95% CI: 0.2 to 3.8) overestimated BF%, whereas BIA by Valhalla Scientific (-2.6
      BF%, 95% CI: -4.5 to -0.6) and skinfold equations by Jackson et al. (-1.20, 95%
      CI: -2.3 to -0.1) showed a relative underestimation. The mean bias for the
      skinfold equation by Durnin & Womersley, against UWW, was 0.0 BF% (95% CI: -1.3
      to 1.3). The correlation between the size of measurement and the mean difference
      was significant for only NIR (r = -0.77, P = 0.003). CONCLUSIONS: The difference
      between any method and UWW is dependent on the study. However, some methods have
      a systematical tendency for relative over- or underestimation of BF%.

PMID- 11248874
TI  - Factors affecting iron stores in infants 4-18 months of age.
AB  - OBJECTIVES: To determine the effects of dietary, physiological or environmental
      factors on body iron levels in infants aged 4-18 months. DESIGN: The daily iron
      intake of the infants was measured from a diet history obtained by interview
      using a standardised question sheet, previously validated against weighed intake
      (minimum 3 days) in an independent sample of 8 and 18 month old infants.
      Capillary blood samples were analyzed for haemoglobin, mean cell volume,
      haematocrit, zinc protoporphyrin and plasma ferritin concentration. Ferritin
      values were log-transformed prior to analysis to give a better approximation to
      the normal distribution and forward stepwise multiple linear regression was
      carried out using SPSS. SETTING: The city of Norwich, UK and some of its suburbs.
      SUBJECTS: One hundred and eighty-one healthy infants in age groups 4, 8, 12 and
      18 months. RESULTS: Main determinants of iron stores in the 4 month old infants
      were birth weight (+ve (P < 0.001)) and body weight (-ve (P < 0.005)). In the 8
      month old infants intake of cow's milk (-ve (P < 0.05)), belonging to a smoking
      household (-ve (P < 0.05)) and quantity of commercial babyfood consumed (+ve (P <
      0.05)) were significant. In this age group there was a gender effect (girls >
      boys (P < 0.01)) and the gender effect remained at 12 months (girls > boys (P <
      0.05)), but at 18 months only non-haem iron intake was a significant factor (-ve
      (P < 0.05)). CONCLUSIONS: At 4 months of age birth weight and body weight exert
      the greatest influence on iron stores, whereas by 8 months components of the
      weaning diet have an effect (commercial babyfood (+ve), cow's milk (-ve)); there
      is also a gender effect (girls > boys), possibly reflecting the different growth
      rate between boys and girls. At 12 and 18 months the only significant factors are
      gender (girls > boys) and non-haem iron intake (-ve) respectively.

PMID- 11248875
TI  - Urinary 5-L-oxoproline (pyroglutamic acid) excretion is greater in infants in
      Jamaica than in infants in England.
AB  - OBJECTIVE: To determine the pattern of excretion in urine of 5-L-oxoproline, as a
      measure of glycine status, during the first six weeks of life in Jamaican
      infants. DESIGN: Spot samples of urine were collected from term and preterm
      infants at birth and longitudinally to four weeks of age, or at six weeks of age.
      5-L-oxoproline was isolated by column chromatography and hydrolysed to L-glutamic
      acid, which was measured enzymatically and the results expressed relative to
      creatinine excretion. SETTING: Maternity wards and postnatal clinic of the
      University Hospital of the West Indies. SUBJECTS: African-Caribbean infants, 19
      term and 21 preterm, from birth to four weeks of age, and 79 term infants at six
      weeks of age. RESULTS: There were no differences between term and preterm
      infants. Excretion of 5-L-oxoproline increased progressively from birth, 141
      mumol/mmol creatinine, to 270 mumol/mmol creatinine at four weeks of age. At six
      weeks of age, excretion was significantly greater than at birth or four weeks of
      age, 525 mumol/mmol creatinine. Compared with infants born in England, the
      excretion of 5-L-oxoproline was not different at birth, but was significantly
      greater in Jamaican infants at six weeks of age. CONCLUSIONS: Glycine status,
      indicated by increased excretion of 5-L-oxoproline, is marginal in Jamaican
      infants at six weeks of age, and this possibly reflects a limitation in the
      endogenous biosynthesis of glycine due to a dietary limitation of folate or
      vitamin B-12.

PMID- 11248876
TI  - Para-aminobenzoic acid used as a marker for completeness of 24 hour urine:
      assessment of control limits for a specific HPLC method.
AB  - OBJECTIVE AND DESIGN: The study comprised three protocols. Protocol 1 compared a
      HPLC method with the commonly employed colorimetric diazocoupling method.
      Protocol 2 examined, if the last dosage of p-aminobenzoic acid (PABA) could be
      advanced in the old to allow for a delayed age-dependent urinary excretion of
      PABA. Protocol 3 established limits for recovery of PABA in 24 h urine applying
      the HPLC method. SUBJECTS AND SETTING: A total of 151 healthy volunteers
      participated in the study of which 140 were accepted. In protocol 1: 37 subjects
      aged 20-78 y were included. All subjects took PABA as recommended (80 mg orally
      at 08.00, 12.00 and 18.00 h). Protocol 2: compared urinary PABA excretion in two
      groups of 80 y old subjects who had their last PABA dosage administered at 15.00
      h (n = 16) and at 18.00 h (n = 31), respectively. Protocol 3: comprised 56
      subjects aged 20-80 y. In the younger age group (20-59 y; n = 34) PABA was taken
      as recommended, whereas in the older age group (60-80 y; n = 22) the last PABA
      dosage was advanced three hours. RESULTS: Protocol 1: HPLC gave significantly
      lower PABA recovery results compared to colorimetry, the difference between
      methods being 23.9 +/- 8.5 mg/24 h (P < 0.001). Protocol 2: higher PABA
      recoveries were demonstrated with the advanced dosage schedule compared to the
      recommended schedule (208 +/- 14 mg/24 h vs 181 +/- 22 mg/24 h; P < 0.001).
      Protocol 3: PABA recovery with HPLC was 211 +/- 12 mg/24 h, and the lower limit
      comprising 95% of subjects was 187 mg/24 h. Similar PABA recoveries were
      demonstrated in the younger subjects and the older subjects (211 +/- 11 mg/24 h
      vs 211 +/- 13 mg/24 h; NS). CONCLUSION: An advanced dosage schedule for PABA in
      the aged is recommended. Because of lower recoveries with HPLC, the low limit for
      recovered PABA in a complete 24 h urine differs from the limit based on
      colorimetry. This study found a limit of 187 mg/24 h corresponding to the lower
      95% confidence limit for a single subject.

PMID- 11248877
TI  - Effects of preterm infant formula supplementation with alpha-linolenic acid with
      a linoleate/alpha-linolenate ratio of 6: a multicentric study.
AB  - OBJECTIVE: To investigate the effects of a milk formula supplemented with a alpha
      linolenic acid (ALA) (18:2 n-6/18:3 n-3 ratio near 6/1) on plasma and red blood
      cell (RBC) fatty acids (FAs) in premature infants and compare with a non
      supplemented formula (18:2 n-6/18:3 n-3 = 22/1). DESIGN AND SUBJECTS: Infants of
      mothers who elected not to breast-feed were randomly assigned to either a high
      alpha linolenic formula (HLF: n = 31) group or a low alpha-linolenic formula
      (LLF: n = 32) control group. Infants fed human milk (HM: n = 25) were enrolled
      concurrently as a reference group. Anthropometric and biological measurements
      were made after two days (D2) and 15 d (D15) of enteral feeding and at the 37th
      week (W37) of postconceptual age. In HLF, the 18:3 n-3 content was 1.95% of total
      FAs (0.77% of total energy) and the 18:2 n-6/18:3 n-3 ratio was near 6/1. In LLF,
      the 18:3 n-3 content was 0.55% of total FAs (0.22% of total energy) and the 18:2
      n-6/18:3 n-3 ratio was 22/1. RESULTS: ALA supplementation had minimal effect on
      the n-6 series, did not alter the anthropometric data and confirmed the
      conversion of ALA into docosahexaenoic acid (DHA). Throughout the study, it
      maintained, the RBC membrane DHA values within the confidence interval of those
      obtained in the HM group. Such was not the case with LLF CONCLUSION: alpha
      linolenic acid supplementation (from Rapeseed oil and in a 18:2 n-6/18:3 n-3
      ratio = 6) in premature infant formula can contribute efficiently to the
      maintenance of the n-3 status in the premature newborns.

PMID- 11248878
TI  - Interesterification of fats in margarine: effect on blood lipids, blood enzymes,
      and hemostasis parameters.
AB  - OBJECTIVES: In 60 healthy humans, a blend of commonly used edible vegetable fats
      was compared with the same fat blend after random chemical interesterification,
      for their effects in terms of nutritional safety on blood lipids, blood enzymes
      and hemostasis parameters. DESIGN: Both fat blends were supplied double-blind at
      two energy levels (4 and 8% of energy) in margarine according to a parallel
      design. At either energy level, the two fat blends were consumed according to a
      cross-over design for two periods of three weeks, without an intermediate wash
      out period. RESULTS: The 30 parameters studied revealed no statistically
      significant differences between the two fat blends, except for slightly
      (approximately 10%) lower D-dimers concentrations after consumption of the
      interesterified fat blend. CONCLUSIONS: Increased levels of the fibrin
      degradation products D-dimers are positively associated with risk for coronary
      heart disease. Thus, it was concluded that the inclusion of a chemically
      interesterified vegetable fat blend in the diet of healthy people does not
      influence fasting blood lipids, blood enzymes and/or hemostasis parameters in an
      adverse way, when compared with a non-interesterified fat blend with the same
      fatty acid composition.

PMID- 11248879
TI  - Ten year trends in the dietary habits of Danish men and women. Cohort and cross
      sectional data.
AB  - OBJECTIVE: To describe 10 year trends and individual changes in food habits of
      Danish men and women in relation to dietary recommendations using data from both
      a cohort and a repeated cross-sectional study, and to examine whether the two
      sampling methods give similar results. DESIGN: Baseline data were collected in
      1982-1984 and respectively repeated measurements for cohort and cross-sectional
      changes in food habits. SETTING: The County of Copenhagen, Denmark. SUBJECTS: Men
      and women aged 30-70y in 1982-1984, 1986-1988 and 1992-1994. The trend analyses
      included 3785 subjects for cohort and 7316 for cross-sectional study,
      respectively. Longitudinal changes were studied among 2430 individuals with food
      data from all three examinations. METHODS: Food intakes were estimated using a
      short food frequency questionnaire. RESULTS: During the study period both men and
      women reported a decreased intake frequency of animal and vegetable fats, milk,
      eggs, meat products, white bread and potatoes, while they had increased intakes
      of low-fat margarine, fruit, raw vegetables, coarse breads, oatmeal, pasta, rice,
      cakes and candy. In both men and women the decrease in the consumption frequency
      of, white bread and potatoes, and the increase in pasta, and candy, were higher
      in the younger than in the older age group. In contrast, the increased
      consumption frequency of coarse breads, and oatmeal were most pronounced in the
      older age groups. For most foods the cohort and the repeated cross-sectional
      surveys gave similar results. CONCLUSIONS: From 1982 through 1994 the food habits
      of middle-aged Danish men and women changed in the direction of a more healthy
      diet as recommended by health authorities. With the limitation of a possible
      reporting bias both the cohort and repeated cross-sectional study designs may be
      used for monitoring changes in food intake.

PMID- 11248880
TI  - Are awareness of dietary fat intake and actual fat consumption associated?--a
      Dutch-American comparison.
AB  - OBJECTIVES: To compare dietary fat intake, the accuracy of individuals' awareness
      about their fat intake, and sociodemographic and psychosocial correlates of
      awareness, in Dutch and American samples of employed adults. A discrepancy
      between objective dietary intake data and subjective self-evaluation of dietary
      fat consumption has been recognized in the past and might undermine healthy diet
      promotion interventions, and this is important because people who believe that
      their diets are healthful are less likely to be interested in making changes.
      Further, international comparisons have not been examined to date. DESIGN: Data
      collected for the baseline surveys of the 'Healthy Bergeijk' study in the
      Netherlands and the 'Working Well Trial' in the United States were compared.
      SUBJECTS: Working adults from a Dutch community health intervention study (n =
      768) and an American worksite health promotion trial (n = 15,440). MAIN OUTCOME
      MEASURES: Objectively assessed dietary fat intake, measured by food frequency
      questionnaires, and subjective ratings of fat intake (self-rated fat intake).
      RESULTS: Findings show that the Dutch respondents had higher objectively assessed
      fat intake and lower subjective ratings of fat intake (P < 0.001). American
      respondents perceived their diets as higher in fat, more often stated their
      intentions to reduce fat intake, and were slightly more likely to make realistic
      estimates of their dietary fat. Dutch subjects were significantly more likely to
      underestimate their fat intakes. In both samples, women were most likely to
      underestimate their fat consumption and the most educated persons were most
      likely to be realistic. CONCLUSIONS: A substantial proportion of adults, both in
      the United States and the Netherlands, lack accurate awareness about how much fat
      they consume, though errors tend to be in opposite directions in the two
      countries. This study is an important first step toward broadening our
      international understanding of human dietary behavior for disease prevention.

PMID- 11248881
TI  - Relation between birth order and the maternal and neonatal docosahexaenoic acid
      status.
AB  - OBJECTIVE: To investigate whether succeeding pregnancies will affect the maternal
      and neonatal docosahexaenoic acid (DHA, 22:6n-3) status. DESIGN: Cross-sectional
      study. SUBJECTS: Women who were pregnant for the 1st to 7th time and took part in
      a longitudinal study to investigate the essential fatty acid status of pregnant
      women and their infants. The total study population comprised 98 primigravidae
      (PG) and 146 multigravidae (MG). MAIN OUTCOME MEASURES: Fatty acid profiles of
      phospholipids isolated from maternal plasma samples collected during pregnancy
      and after delivery, and of umbilical plasma, vein and artery, obtained
      immediately after birth. RESULTS: The absolute (mg/L) and relative (% of total
      fatty acids) amounts of DHA in maternal plasma phospholipids (PL) were
      significantly lower in MG than in PG. In addition, a significant negative
      correlation was observed between gravida number and the DHA content in maternal
      plasma samples. The DHA deficiency index (22:5n-6/22;4n-6) was significantly
      higher and the DHA sufficiency index (22:6n-3/22:5n-6) was significantly lower in
      umbilical plasma of infants born of MG than in that of infants born of PG. The
      relative DHA content of umbilical artery and vein vessel walls was significantly
      lower in MG- than in PG-neonates and significant negative associations were
      observed between birth order and the relative amounts of DHA in cord tissues.
      CONCLUSIONS: These results indicate that the maternal DHA status becomes reduced
      after each following pregnancy, which may result in a lower neonatal DHA status.
      Whether or not this has also functional consequences needs to be investigated
      further.

PMID- 11248882
TI  - Administration of low doses of fish oil derived N-3 fatty acids to elderly
      subjects.
AB  - OBJECTIVES: To assess the incorporation of n-3 polyunsaturated fatty acids (PUFA)
      in plasma and erythrocyte lipids of elderly subjects after ingestion of very low
      doses of fish oil. The effects on alpha-tocopherol and retinol concentrations
      were also studied. SETTING: Municipal nursing home in Barcelona, Spain. SUBJECTS:
      Forty-five elderly subjects aged 60-92 y. DESIGN AND INTERVENTION: Subjects
      received a non-commercialized milk formula containing 1% fish oil for 15 months,
      which provided 0.40 g/d of n-3 PUFA. Fatty acid profiles and antioxidant
      concentrations were measured before and after the intervention period. RESULTS:
      Fish oil ingestion was associated with significant increases in total n-3 PUFA in
      plasma and erythrocytes by 32% and 18%, respectively. Eicosapentaenoic (EPA) and
      docosahexaenoic (DHA) acid concentrations were higher after the ingestion period
      both in plasma and erythrocytes (P < 0.05), whereas linoleic and arachidonic
      acids remained unchanged. The n-6/n-3 ratio decreased by 21% in plasma and by 16%
      in erythrocytes (P < 0.05). Moreover, younger subjects showed a greater
      incorporation of EPA and DHA than older subjects. Plasma alpha-tocopherol and
      retinol concentrations did not vary significantly, whereas erythrocyte alpha
      tocopherol was significantly higher after the intervention period. CONCLUSION:
      This study shows that low doses of n-3 PUFA supplemented with adequate amounts of
      alpha-tocopherol can be incorporated into blood lipids in elderly subjects
      without lowering their antioxidant concentrations.

PMID- 11248883
TI  - A population-based study of the relationship between salt intake, bone resorption
      and bone mass.
AB  - OBJECTIVE: To explore the relationship between urinary sodium (the best measure
      of salt intake), urinary calcium, urinary deoxypyridinoline (DPYR) and bone mass.
      DESIGN: Cross-sectional study. SETTING: Population based sample of healthy Hobart
      residents. SUBJECTS: One hundred and fifty-four (M = 34, F = 120) subjects
      invited to take part from a systematic sample of the electoral roll and a single
      newspaper advertisement. RESULTS: In both sexes, urinary sodium correlated
      moderately with urinary DPYR (r = 0.32, P < 0.0001) and urinary calcium (r =
      0.37, P < 0.0001). In multivariate analysis, the combination of urinary sodium,
      total body bone area, age and sex explained 22% of the variation in log
      transformed DPYR (P < 0.00001). In univariate analysis, both urinary sodium and
      urinary DPYR were strongly associated with bone mineral content and bone mineral
      density at all sites but this association disappeared after adjustment for
      confounders particularly body weight. CONCLUSIONS: This study has shown that salt
      intake is associated with markers of bone resorption in a population-based sample
      of males and females and appears likely to be a risk factor for osteoporosis
      despite the lack of a demonstrable association between bone mass and a single
      measure of urinary sodium excretion. Further studies are needed to define the
      effect of salt intake on bone mass and fractures more clearly. These studies will
      need to be either longitudinal or interventional in design with repeated measures
      of urinary sodium so that habitual sodium intake can be accurately assessed and
      regression dilution bias can be minimised.

PMID- 11248884
TI  - Electrokinetic injection for stacking neutral analytes in capillary and microchip
      electrophoresis.
AB  - An on-column mechanism for electrokinetically injecting long sample plugs with
      simultaneous stacking of neutral analytes in capillary electrokinetic
      chromatography is presented. On-column stacking methods allow for the direct
      injection of long sample plugs into the capillary, with narrowing of the analyte
      peak width to allow for an increase in the detected signal. Low-pressure
      injections (approximately 50 mbar) are commonly used to introduce sample plugs
      containing neutral analytes. We demonstrate that injection can be accomplished by
      applying an electric field from the sample vial directly into the capillary, with
      neutral analytes injected by electroosmotic flow at up to 1 order of magnitude
      faster than the corresponding pressure injections. Since stacking occurs
      simultaneously with electrokinetic injection, stacking is initiated at the
      capillary inlet, resulting in an increased length of capillary remaining for
      separation. Reproducibility obtained for peak height and peak area with
      electroosmotic flow injection is comparable to that obtained with the pressure
      injection mode, while reproducibility of analysis time is markedly improved.
      Electrokinetic stacking of neutral analytes utilizing electroosmotic flow is
      demonstrated with discontinuous (high conductivity, high mobility) as well as
      continuous (equal conductivity, equal mobility) sample electrolytes. Injecting
      neutral analytes by electroosmotic flow affords a 10-fold or greater decrease in
      analysis times when capillaries of 50-microm i.d. or smaller are used. This
      stacking method should be exportable to dynamic pH junction stacking and
      electrokinetic chromatography with capillary arrays. Equations describing this
      electrokinetic injection mode are introduced and stacking of a neutral analyte on
      a microchip by electrokinetic injection using a simple cross-T channel
      configuration is demonstrated.

PMID- 11248885
TI  - Multispectral imaging microscope with millisecond time resolution.
AB  - A new multispectral imaging microscope with micrometer spatial resolution and
      millisecond temporal resolution has been developed. The imaging microscope is
      based on the use of an acousto-optic tunable filter (AOTF) for spectral tuning
      and a progressive scan camera capable of snapshot operation for recording. It can
      operate in two modes: images are recorded as a function of time or wavelength.
      When operated as a function of time, the microscope is configured so that as many
      images as possible are recorded, grabbed, and stored per one wavelength. Upon
      completion, the AOTF is scanned to a new wavelength, and a new set of images are
      recorded. Up to 33 images/ second (i.e., 30 ms/image) can be recorded in this
      mode. In the other configuration, the recording wavelength is rapidly scanned (by
      means of the AOTF) and only one image is rapidly recorded, grabbed, and stored
      for each wavelength. Because additional time is needed to scan the AOTF, the
      maximum number of images can be grabbed in this case is 16 frames/s. Preliminary
      applications of the imaging microscope include measurements of photoinduced
      changes of a single unit cell in temperature-sensitive cholesteric liquid
      crystals as a function of time and wavelength. The changes were found to be
      varied with time and wavelength. Interestingly, the photoinduced changes of unit
      cells in the liquid crystal are not the same but different from cell to cell.
      This imaging microscope is particularly useful for measurements of small-size
      samples that undergo rapid chemical or biochemical reactions, e.g., activities of
      a single biological cell.

PMID- 11248886
TI  - Solubility of triazine pesticides in pure and modified subcritical water.
AB  - Solubility measurements in pure and modified water serve as a basis for
      optimizing the subcritical water extraction of target analytes such as food
      contaminants. The solvent strength of the water is affected by both the system's
      temperature and the amount and type of cosolvent modifier that is added to the
      water, which causes a reduction in the dielectric constant of water. In the
      present work, the solubilities of the triazine pesticides atrazine, cyanazine,
      and simazine were measured in pure and modified water at temperatures ranging
      from 50 to 125 degrees C and at a pressure of 50 atm. The solubility data were
      obtained using a static solubility apparatus with on-line liquid chromatographic
      (LC) detection. By increasing the temperature of the water, the solubilities of
      the triazine pesticides increased approximately 3-fold in pure water for each 25
      degrees C temperature increment. Cyanazine was 5 times more soluble than atrazine
      and an order of magnitude more soluble than simazine at 100 degrees C. The
      solubility of atrazine was also measured in ambient and hot water modified with
      ethanol and urea. At 100 degrees C, the solubility of atrazine is doubled when
      the water is modified with urea, and is increased over an order of magnitude when
      ethanol is used as modifier. The data, therefore, indicate that adding a
      cosolvent to water in addition to increasing the system temperature increases the
      solubilities of triazine pesticides in subcritical water. It was further
      determined that the solutes do not thermally degrade or hydrolyze at the
      temperatures reported in this study.

PMID- 11248887
TI  - Characterization of the protein subset desorbed by MALDI from whole bacterial
      cells.
AB  - This study characterizes various features of the proteins that are detected in
      MALDI mass spectra when whole bacteria cells are analyzed, in an effort to
      understand why some proteins are successfully detected and many others are not.
      Forty peaks observed in the mass range 4,000-20,000 Da in the spectra of
      Escherichia coli K-12 and 11775 are tentatively assigned to proteins in a protein
      database, and these proteins are characterized by cell location, copy number, pI,
      and hydropathicity. Those detected originate in the cytosol and generally share
      the traits of high abundance within the cell, strong bacisity, and medium
      hydrophilicity.

PMID- 11248888
TI  - Lectin and carbohydrate affinity capture surfaces for mass spectrometric analysis
      of microorganisms.
AB  - In a preliminary report (Bundy, J. L.; Fenselau, C. Anal. Chem 1999, 71, 1460
      1463), we demonstrated the use of lectin-derivatized surfaces to capture and
      concentrate complex carbohydrates as well as microorganisms from sample matrixes
      unamenable to direct MALDI mass spectrometry. Here, we extend the work to include
      samples representative of a wider variety of microorganisms of importance to
      human health and of enveloped viruses. In this study, lectins were immobilized
      directly to a membrane surface via primary amines. A complementary approach was
      also explored, using immobilized carbohydrates to capture bacteria via microbial
      lectins expressed on their surfaces. The carbohydrate-based surfaces were
      constructed by first immobilizing streptavidin to the membrane, followed by
      attachment of a commercially produced biotin/carbohydrate polymer. Acid treatment
      of the sample prior to mass spectrometric analysis permits the observation of
      protein biomarkers from the captured microbial samples in the 5-20 kDa mass
      range. Bacteria samples were detected from physiological buffers, urine, milk,
      and processed chicken samples using the biocapture probes. Viral samples were
      detected from culture based on glycoprotein moieties desorbed directly from the
      surface. The carbohydrate-based system provided greater sensitivity than the
      lectin system, possibly due to the larger number of accessible saccharide ligands
      on the polymer.

PMID- 11248889
TI  - Palladium film decoupler for amperometric detection in electrophoresis chips.
AB  - Demonstrated in this article is that a palladium metal film can be applied to
      decouple the electric circuitry of electrochemical detection from that of the
      electrophoretic separation in an electrophoresis chip. The Pd solid-state field
      decoupler, as well as the working electrodes, is thermally evaporated onto the
      plastic chip and oriented vertically across the separation channel. After the
      sample zones flow over the Pd decoupler, their electrochemical response is
      measured at working electrodes in the downstream pathway. Because the electrodes
      are on the separation channel, the electrode channel alignment is no longer a
      problem. For a separation channel of roughly 200 microm in width and 75 microm in
      depth in 10 mM phosphate (pH 5.1), the noise level at the working electrode is <
      15 pA at an electric field of 570 V/cm.

PMID- 11248890
TI  - Electrochemiluminescence determination of 2',6'-difluorophenyl 10-methylacridan-9
      carboxylate.
AB  - Electrochemical oxidation of the acridan 2',6'-difluorophenyl 10-methylacridan-9
      carboxylate produces the corresponding acridinium ester, which reacts with
      hydrogen peroxide forming a dioxetanone intermediate. Decomposition of the
      dioxetanone generates light at 430 nm when it relaxes to the ground state. The
      effect of pH and hydrogen peroxide concentration on this ECL reaction and on the
      stability of the acridan were investigated. At pH 8.0 and a hydrogen peroxide
      concentration of 10 mM, light emission from the ECL reaction was used to
      determine the acridan concentration with a detection limit of 54 pmol L(-1).
      Results suggest that acridan esters could be used as labels in ECL immunoassays
      and nucleotide assays.

PMID- 11248891
TI  - pH-switchable, ion-permselective gold nanotubule membrane based on chemisorbed
      cysteine.
AB  - An electroless gold plating method was used to deposit Au nanotubules within the
      pores of a polycarbonate template membrane. pH-switchable ion-transport
      selectivity was introduced by chemisorbing L-cysteine to the inside tubule walls.
      At low pH, where both the amino and carboxyl groups of the cysteine are
      protonated, these membranes preferentially reject cations and transport anions.
      At high pH, where both the amino and carboxyl groups are deprotonated, these
      membranes preferentially reject anions and transport cations. At pH = 6.0, near
      the isoelectric point of the chemisorbed cysteine, these membranes show neither
      cation nor anion transport selectivity. In addition to this electrostatically
      based selectivity, because of the small inside diameter of the Au nanotubules (as
      small as 0.9 nm), these membranes show molecular-size-based selectivity.

PMID- 11248892
TI  - Microflow-based automated chemistries: application to protein sequencing.
AB  - We describe a microflow-based instrument, consisting of multiple rotary valves,
      capillary tubing, and miniaturized reaction vessels, for the purpose of
      performing automated chemical and biochemical reations on a very small scale
      (i.e. submicroliter volumes). The novelty is that close to 100% of the reaction
      end products are available in a minimal volume (< or = 5 microL) inside a
      pressurized microvial for subsequent analysis. This makes the system compatible
      with capillary HPLC and, in principle, with continuous-flow nanoelectrospray mass
      spectrometry. Total control of flow path combinations and directions,
      temperatures, and gas pressures enables precise execution of complex biochemical
      laboratory procedures. Instrument performance was convincingly demonstrated by
      partially sequencing 100 fmol of an intact protein using classical Edman
      chemistry in combination with capillary-bore liquid chromatography. To our
      knowledge, this is the smallest amount of protein ever reported to be
      successfully analyzed in this way. Additional applications that merge enzymatic
      and chemical procedures with high-sensitivity analytical devices can be
      envisioned in the future.

PMID- 11248893
TI  - Nanoengineered structures for holding and manipulating liposomes and cells.
AB  - We describe the fabrication of nanoengineered holding pipets with concave seating
      surfaces and fine pressure control. These pipets were shown to exhibit
      exceptional stability in capturing, transporting, and releasing single cells and
      liposomes 1-12 microm in diameter, which opens previously inaccessible avenues of
      research. Three specific examples demonstrated the utility and versatility of
      this manipulation system. In the first, carboxyrhodamine was selectively
      incorporated into individual cells by electroporation, after which nearly all the
      medium (hundreds of microliters) surrounding the docked and tagged cells was
      rapidly exchanged (in seconds) and the cells were subsequently probed by laser
      induced fluorescence (LIF). In the second study, a single liposome containing
      carboxyrhodamine was transported to a dye-free solution using a transfer pipet,
      docked to a holding pipet, and held firmly during physical agitation and
      interrogation by LIF. In the third study, pairs of liposomes were positioned
      between two microelectrodes, held in contact, and selectively electrofused and
      the resulting liposomes undocked intact.

PMID- 11248894
TI  - Performance evaluation of an in-injection port thermal desorption/gas
      chromatographic/negative ion chemical ionization mass spectrometric method for
      trace explosive vapor analysis.
AB  - A gas chromatographic method utilizing thermal desorption of Tenax TA and sol-gel
      sorbent traps has been developed and validated for the analysis of trace
      explosive vapor with negative ion chemical ionization mass spectrometric
      detection. Sorbent tubes were packed with Tenax TA and sorbent particles prepared
      in-house by the sol-gel process. Thermal desorption was performed within a
      split/splitless injection port with minimal instrument modification. Performance
      was characterized by relative thermal desorption recovery, precision
      (reproducibility), linearity of the calibration, and method detection limits.
      Method validation was performed with a series of dinitrotoluenes, dinitrobenzene,
      trinitrotoluene, trinitrobenzene, two aminodinitrotoluenes, three nitroesters,
      and two nitramines. The performance of Tenax TA and the sol-gel sorbents is
      evaluated based on the method validation data. The method was applied to the
      analysis of trace explosive vapor collected and concentrated with sol-gel solid
      sorbent traps from the headspace of a smokeless gunpowder sample.

PMID- 11248895
TI  - Reduction of nonpolar amino acids to amino alcohols to enhance volatility for
      high-precision isotopic analysis.
AB  - Amino acids are routinely derivatized using carbon-containing groups prior to gas
      chromatography continuous-flow isotope ratio mass spectrometry (GCC-IRMS).
      Derivative C contaminates analyte C because the entire derivatized compound is
      combusted to CO2. Correction procedures are required to extract the analyte
      isotope ratio. We present a method for reduction of six nonpolar amino acids to
      their corresponding amino alcohols, demonstrate a GC strategy to produce
      acceptable peak shapes from the resulting strongly H-bonding analytes, and
      present isotopic analysis for amino acids and their corresponding amino alcohols
      to evaluate any possible isotopic fractionation. Alanine, valine, leucine,
      isoleucine, methionine, or phenylalanine was reduced using NaBH4 in THF with I2
      as an electrophile. Reactions were performed with 2 g of analyte to permit
      isotopic analysis by conventional elemental analysis-IRMS. All reactions were
      quantitative as assessed by IR spectra, melting points, and GC. Recovery from the
      reaction mixture was 60-84%. GC separation of a mixture of the six amino alcohols
      was achieved using a thick stationary-phase (5 microm) capillary column to avoid
      tailing due to hydrogen bonding to the walls of the fused-silica capillary. The
      reproducibility of GCC-IRMS determinations of amino alcohols averaged SD(613C) =
      0.25 +/- 0.19%. The absolute differences between delta13C of amino acids measured
      by an elemental analyzer coupled to IRMS and amino alcohols measured by GCC-IRMS
      was delta613C = 0.14% and showed no general trend. Reactions performed with 2 mg
      of analyte yielded equivalent chromatograms. These data indicate that the
      reduction method does not induce isotopic fractionation and can be used for
      continuous-flow isotopic analysis to avoid addition of contaminating carbon.

PMID- 11248896
TI  - Chemical and on-line electrochemical reduction of metalloproteins with high
      resolution electrospray ionization mass spectrometry detection.
AB  - The observation of the reduced forms of several metal-containing proteins using
      electrospray ionization (ESI) is reported for the first time. High-resolution
      mass analysis using Fourier transform ion cyclotron resonance mass spectrometry
      allows the oxidized and reduced forms of the proteins to be distinguished. The
      metalloproteins are reduced both chemically and electrochemically. Under normal
      sample handling conditions, the proteins that are reduced in solution appear in
      their oxidized form in their ESI mass spectra. Rigorous exclusion of oxygen from
      the solution of the reduced protein allows the observation of the reduced form in
      the gas phase. The metal centers investigated include heme and non-heme iron
      proteins, copper, and a manganese-substituted iron-sulfur cluster of the form
      [3FeMn-4S]. The electrochemical method is shown to provide several advantages
      over chemical reduction. The oxidation state of the metal center is stable with
      respect to electrospray ionization in both positive and negative ionization
      modes.

PMID- 11248897
TI  - Nonresonant MALDI of oligonucleotides: mechanism of ion desorption.
AB  - Oligonucleotide ions have been detected using matrix-assisted laser
      desorption/ionization (MALDI) under nonresonant laser irradiation of the sample.
      When mass resolution was not limited by adduct attachment to the analyte ions,
      the nonresonant MALDI spectra demonstrated better resolution than the spectra
      acquired with resonant ultraviolet irradiation. We found that preparation of thin
      film samples on absorbing substrate surfaces was critical for the success of NR
      MALDI. The possible acoustic mechanisms of ion formation and desorption are
      discussed.

PMID- 11248898
TI  - A tandem column ensemble with an atmospheric pressure junction-point vent for
      high-speed GC with selective control of peak-pair separation.
AB  - A series-coupled (tandem) ensemble of two capillary GC columns using different
      stationary phases and a pneumatically actuated low-volume valve connecting the
      column junction point to an atmospheric-pressure vent line is used to adjust the
      ensemble separation of selected pairs of target compounds. The valve is normally
      closed, and the pressure at the column junction point assumes the value that
      would occur in the absence of any other connections. The valve can be opened for
      brief periods of time, thus producing pulses of atmospheric pressure at the
      column junction point. If a component pair is separated by the first column but
      coelutes from the column ensemble, the ensemble separation can be increased if a
      pulse occurs when one of the components has migrated across the column junction
      but the second component is still on the first column. All of the mixture
      components that are on the same column during the time that the valve is open
      (pulse duration) will be shifted to either larger or smaller retention times, but
      the pattern of peaks (elution order) for these components from the column
      ensemble will be relatively unaffected by the pressure pulse. Multiple pulses can
      be used to enhance the separation of different component pairs, which
      sequentially reach the column junction point. Performance of the valve-operated
      system is described. Time-of-flight mass spectrometry with time-array detection
      is used to examine the effects of pulse duration on the separation achieved for
      different component pairs.

PMID- 11248899
TI  - On-capillary ion-exchange preconcentration of inorganic anions in open-tubular
      capillary electrochromatogrpahy with elution using transient-isotachophoretic
      gradient. 2. Characterization of the isotachophoretic gradient.
AB  - Diffuse transient-isotachophoretic boundaries can be used as an elution gradient
      of increasing eluotropic strength to elute inorganic anions that have been
      preconcentrated on an open-tubular ion-exchange stationary phase prior to
      electrophoretic separation. The generation and characteristics of these gradients
      for elution after preconcentration have been investigated. The gradients are
      generated by placing a low-mobility, weak ion-exchange competing anion in the
      capillary (weak electrolyte, WE), and a high-mobility, strong ion-exchange
      competing anion in the electrolyte vials (strong electrolyte, SE). Application of
      voltage establishes a diffuse boundary with the composition changing from the
      weak anion to the strong anion. Comparison of elution gradients generated with
      different electrolyte systems was accomplished by comparing the eluotropic
      strength (a function of eluent concentration, ion-exchange selectivity
      coefficient, and charge) and the shape of the profile as it changes from WE to
      SE. The ion-exchange selectivity coefficient of the SE competing anion is
      important in establishing a sharp change in elution strength. A large difference
      in mobility between the WE and SE competing anions gives an SE with a higher
      final eluotropic strength, but the slope of the gradient is shallower. This
      results in a reduction in the efficiency of analyte focusing. To ensure maximum
      focusing efficiency, the WE and SE electrolytes should be selected such that the
      SE has the highest possible eluotropic strength for a given concentration of WE.
      The SE competing anion should also have a sufficiently low electrophoretic
      mobility to ensure focusing for the maximum number of analytes, and the mobility
      difference between the WE and SE competing anions should be as small as possible.

PMID- 11248900
TI  - Electroosmotic flow in composite microchannels and implications in microcapillary
      electrophoresis systems.
AB  - The electroosmotic flow in laminated excimer laser-ablated microchannels has been
      studied as a function of the depth of the rectangular channels, and particular
      emphasis has been given to the difference in the zeta-potentials between the
      lamination layer and the ablated substrate. Experimental electroosmotic flow
      follows the tendency predicted by a recently published model. The zeta-potentials
      of lamination and ablated surfaces were determined for poly(ethylene
      terephthalate) and poly(carbonate) substrates by fitting the experimental data
      with a numerical implementation of this model. In the experimentally investigated
      range of channel cross sections, a linear fit to the data gives a good
      approximation of the zeta-potentials for both materials. Moreover, a flow
      injection analysis of fluorescein dye has been performed to show the severe loss
      in numbers of theoretical plates, caused by Taylor dispersion, when such
      microchannels, dedicated to microcapillary electrophoresis, are used.

PMID- 11248901
TI  - Analysis of self-assembled cationic lipid-DNA gene carrier complexes using flow
      field-flow fractionation and light scattering.
AB  - Self-assembled cationic lipid-DNA complexes have shown an ability to facilitate
      the delivery of heterologous DNA across outer cell membranes and nuclear
      membranes (transfection) for gene therapy applications. While the size of the
      complex and the surface charge (which is a function of the lipid-to-DNA mass
      ratio) are important factors that determine transfection efficiency, lipid-DNA
      complex preparations are heterogeneous with respect to particle size and net
      charge. This heterogeneity contributes to the low transfection efficiency and
      instability of cationic lipid-DNA vectors. Efforts to define structure-activity
      relations and stable vector populations have been hampered by the lack of
      analytical techniques that can separate this type of particle and analyze both
      the physical characteristics and biological activity of the resulting fractions.
      In this study, we investigated the feasibility of flow field-flow fractionation
      (flow FFF) to separate cationic lipid-DNA complexes prepared at various lipid-DNA
      ratios. The compatibility of the lipid-DNA particles with several combinations of
      FFF carrier liquids and channel membranes was assessed. In addition, changes in
      elution profiles (or size distributions) were monitored as a function of time
      using on-line ultraviolet, multiangle light scattering, and refractive index
      detectors. Multiangle light scattering detected the formation of particle
      aggregates during storage, which were not observed with the other detectors. In
      comparison to population-averaged techniques, such as photon correlation
      spectroscopy, flow FFF allows a detailed examination of subtle changes in the
      physical properties of nonviral vectors and provides a basis for the definition
      of structure-activity relations for this novel class of pharmaceutical agents.

PMID- 11248903
TI  - Neurovisual rehabilitation in Balint's syndrome.

PMID- 11248902
TI  - Needle-type dual microsensor for the simultaneous monitoring of glucose and
      insulin.
AB  - A miniature needle-type sensor suitable for the simultaneous amperometric
      monitoring of glucose and insulin is described. The integrated microsensor
      consists of dual (biologically and chemically) modified carbon-paste working
      electrodes inserted into a 14-guage needle. The glucose probe is based on the
      biocatalytic action of glucose oxidase, and the insulin one relies on the
      electrocatalytic activity of ruthenium oxide. The analytical performance of the
      dual sensor is assessed under flow injection conditions. The needle dual detector
      exhibits a very rapid response to dynamic changes in the concentrations of
      glucose and insulin. No apparent cross reactivity is observed in mixtures
      containing millimolar glucose levels and nanomolar insulin concentrations. The
      response is highly linear (to at least 1000 nM insulin and 14 mM glucose) and
      reproducible (RSD = 2.6-4.1%). The combination microsensor holds great promise
      for real-time measurements of the insulin/glucose ratio and for improved
      management of diabetes.

PMID- 11248904
TI  - Arnold Chiari malformation and nystagmus of skew.

PMID- 11248905
TI  - Botulinum toxin for the treatment of sialorrhoea in ALS: serious side effects of
      a transductal approach.

PMID- 11248906
TI  - Treatment of early onset Parkinson's disease with ropinirole.

PMID- 11248907
TI  - Does disturbed homocysteine and folate metabolism in depression result from
      enhanced oxidative stress?

PMID- 11248908
TI  - Long term follow up after perimesencephalic subarachnoid haemorrhage.

PMID- 11248909
TI  - Idiopathic intracranial hypertension and anticardolipin antibodies.

PMID- 11248910
TI  - Upper gastrointestinal bleeding as a metastatic manifestation of breast cancer: a
      case report and review of the literature.
AB  - CASE PRESENTATION: A 64-year-old woman with known metastatic lobular breast
      cancer presented with fever, epigastric pain, hematemesis, and melena. A
      bleeding, ulcerated gastric metastasis was found and was treated with endoscopic
      therapy, omeprazole, and hormonal therapy. The patient was alive and well 13
      months later. The bleeding was probably precipitated by necrosis of the lesion
      during chemotherapy. DISCUSSION: Gastrointestinal tract metastases from primary
      breast carcinoma are present in 14% to 35% of cases in autopsy series, with
      gastric involvement in 6% to 18% of cases. Recognized much less commonly during
      life than in autopsy studies, they can occur anywhere in the gut and can mimic
      virtually any gastrointestinal disorder. Endoscopy and barium studies facilitate
      diagnosis. Gastric lesions that have been noted include "linitis plastica",
      nodules, polyps, and ulcers. They are usually due to lobular breast carcinoma and
      resemble primary gastric carcinoma on microscopy. Reported cases of bleeding
      gastric metastases have been treated successfully with various local and systemic
      modalities. The median survival time of reviewed cases was four months from
      presentation (with a range of zero to 24 months). CONCLUSIONS: Gastrointestinal
      metastasis is an underdiagnosed complication of breast cancer. Gastrointestinal
      bleeding from metastatic breast cancer is an uncommon presentation that is
      readily diagnosed and that can be treated successfully by endoscopic hemostatic
      therapy.

PMID- 11248911
TI  - Image-guided therapy in urology.
AB  - Technological breakthroughs have advanced the fields of urology, radiology, and
      minimally invasive surgery. Today, the various imaging modalities are
      increasingly applied to guiding therapy. Among the procedures now in use or under
      development are percutaneous cyst drainage or sclerotherapy; tissue ablation with
      high-intensity focused ultrasound, cold, heat, or photon radiation; and conformal
      radiation and brachytherapy. As current limitations are overcome, image-guided
      therapy will expand.

PMID- 11248912
TI  - Laparoscopic infrared imaging.
AB  - BACKGROUND: As an adjunct to direct visual imaging, an infrared endoscope was
      developed to assist in the identification of various anatomic structures and to
      assess tissue viability during laparoscopic procedures. A camera sensitive to
      emitted energy in the mid-infrared range (3 to 5 microm) was incorporated into a
      two-channel visible-light laparoscope. METHODS AND MATERIALS: Laparoscopic
      procedures were performed in a porcine model, inexperienced laparoscopists being
      asked to localize and differentiate structures before dissection using the
      visible-light system and then the infrared system. To determine clinical utility,
      nine laparoscopic urologic procedures were performed with the assistance of the
      infrared system. RESULTS: In the clinical evaluation, infrared imaging proved to
      be useful in differentiating between blood vessels and other anatomic structures.
      In contrast to the experience with the conventional endoscope, vessel
      identification, assessment of organ perfusion, and transperitoneal localization
      of the ureter was successful in all instances using the infrared system. In the
      porcine model, this system also permitted assessment of bowel perfusion during
      laparoscopic occlusion of mesenteric vessels and distinguished between the cystic
      duct and artery. CONCLUSION: Infrared imaging is a potentially powerful adjunct
      to laparoscopic surgery. It may improve the differentiation and localization of
      anatomic structures and allow assessment of physiologic features, such as
      perfusion, not previously attainable with laparoscopic techniques.

PMID- 11248913
TI  - Virtual reality: current urologic applications and future developments.
AB  - The concept of virtual reality (VR) involves the computer generation of
      environments with which a user can interact directly. Virtual reality is now
      being used for medical applications, especially in the area of surgical
      simulation. As technology advances, VR simulation will play an important training
      role for both residents and urologists already in practice. This paper examines
      the history of VR, current developments, and its future implications for the
      field of urology.

PMID- 11248914
TI  - Magnetic resonance imaging in endourology.
AB  - Historically, the utilization of magnetic resonance imaging (MRI) in endourology
      has been limited. The availability of faster and stronger gradient systems has
      given rise to a number of data acquisition strategies that have significantly
      broadened the scope of MRI applications. These methods have led to the evaluation
      of anatomy and function using a single modality, and we describe our experience
      with MRI for comprehensive evaluation of the obstructed ureteropelvic junction.
      We also utilize these new imaging sequences in the investigation of alterated
      renal hemodynamics after extracorporeal shockwave lithotripsy and present our
      preliminary data on the application of MR perfusion imaging as a noninvasive
      technique for the evaluation of renal blood flow.

PMID- 11248915
TI  - CT for the evaluation of flank pain.
AB  - Unenhanced helical CT allows rapid and accurate determination of whether a stone
      is present anywhere in the urinary tract. There is a learning curve for both
      radiologist and urologist, but a number of signs are highly predictive of stone.
      Helical CT scans should always be accompanied by a "scoutogram" to convey an idea
      of what the stone might look like. The scan requires no contrast medium and takes
      only 5 to 10 minutes of imaging time, making it cost effective. It behooves both
      urologists and radiologists to familiarize themselves with the techniques for
      reading these scans.

PMID- 11248916
TI  - Ultrasound in endourology.
AB  - Ultrasonography was first used as a therapeutic aid in endourology in the early
      1970s. Since that time, ultrasound has played an important role, and nowadays,
      interventional ultrasonography is an established procedure in urology. Procedures
      on the kidney, bladder, and prostate, which require different puncture
      techniques, are performed under ultrasound guidance. Today, extracorporeal
      shockwaves for the treatment of stones and Peyronie's disease are applied under
      ultrasonic control. Furthermore, high-intensity focused ultrasound (HIFU) is used
      experimentally for the treatment of renal tumors and, clinically, for the
      treatment of prostate cancer. In urologic emergencies, diagnostic and
      interventional ultrasonography is an important tool. Interventional ultrasound in
      urology has become an outstanding tool for the planning and performance of a
      variety of procedures, and every urologist should be able to use these
      technologies.

PMID- 11248917
TI  - CT and stone fragility.
AB  - Informed selection of treatment requires knowledge of the size and composition of
      a calculus. Spiral CT has a growing role in the detection of calculi, with an
      overall accuracy in excess of 95%. Moreover, the margin of error in determining
      stone size does not exceed 3.6%, and stone volume is underestimated by <5%.
      Pixelograms, the compilation of multiple points of attenuation, may provide clues
      to stone composition and durility.

PMID- 11248918
TI  - Three-dimensional CT of the genitourinary tract.
AB  - The applications of three-dimensional (3D) CT techniques encompass a spectrum
      from calculus disease to preoperative planning. With proper selection of display
      windows and levels, accurate measurement of stone size can be achieved, along
      with volumetric information. A CT scan with reconstruction may help guide the
      direction of an endopyelotomy incision away from crossing vessels. The benefits
      of 3D CT in the evaluation of living renal donors include lower cost and
      decreased patient morbidity. In renal allograft recipients and other patients,
      the study may be used to investigate hypertension. Also, 3D CT is invaluable in
      planning nephron-sparing surgery for renal masses. The ultimate role of this
      modality rests in the hands of clinicians who can benefit from them and the
      radiologists who must provide the high-quality images and the interpretive
      expertise.

PMID- 11248919
TI  - Virtual endoscopy.
AB  - Virtual endoscopy is a technique in which three-dimensional viewing of hollow
      structures is conducted through the utilization of high-resolution imaging and
      unique computer processing methods. The basic components of this technique and
      its applications for urology and other clinical disciplines are reviewed.

PMID- 11248920
TI  - Current urologic applications of digital imaging.
AB  - One of the most significant developments in imaging technology has been the
      process of digitalization. By incorporating currently available digital imaging
      equipment into surgical practice, urologists can be assured of obtaining real
      time video images with optimal clarity and detail. In addition, one can
      efficiently capture and store still images that are crisper and sharper than
      their analog counterparts. These factors greatly improve the diagnostic
      capabilities and organization of today's endourologist.

PMID- 11248921
TI  - Imaging and the Internet.
AB  - Internet-based imaging is changing the way urology services are delivered by
      allowing rapid communication between remote locations. This review focuses on
      Internet-based imaging modalities, the hardware needed to transmit and view these
      images, and current applications. With the continuing expansion of Internet-based
      resources, all physicians must become accustomed to integrating the Internet and
      Internet-based imaging into their practices.

PMID- 11248922
TI  - Telemedicine: recent developments and future applications.
AB  - Telemedicine, or the delivery of health care from a distance, is an exciting
      field that has undergone rapid advancements over the past three decades. Previous
      studies have demonstrated that telemedicine can effectively assist in patient
      care. However, cost issues and the lack of resources to sustain telemedicine
      systems have previously limited the use of this technology. Herein, we explore
      the development, current applications, and future of telemedicine.

PMID- 11248923
TI  - Experience with endoluminal ultrasonography in the urinary tract.
AB  - Ultrasonography has been an invaluable tool in the field of urology for its
      noninvasiveness, safety, and relatively low cost. However, examination of the
      ureter with ultrasound is difficult because of the distance of the transducer
      from the ureter and because of intervening structures such as nonconductive bowel
      gas. As smaller probes have become available, attempts have been made to apply
      them to endoluminal use. Endoluminal ultrasonography has been employed in urology
      to examine the proper placement of injected collagen, diagnose urethral
      diverticula, diagnose and stage upper tract transitional-cell carcinoma, locate
      crossing vessels to guide endopyelotomy, diagnose submucosal calculi, and examine
      the severity and length of ureteral strictures.

PMID- 11248924
TI  - Imaging of the lower urinary tract in adults.
AB  - Imaging of the lower urinary tract is an integral part of everyday urologic
      practice. Clinical application of less commonly used techniques is discussed to
      expand their usefulness in an ambulatory setting.

PMID- 11248925
TI  - Laparoscopic ultrasonography.
AB  - The use of laparoscopic ultrasonography (LUS) allows visualization of tissues
      beyond the two-dimensional laparoscopic picture, enhancing the amount and quality
      of information available to the surgeon. Linear-array transducers with
      frequencies of 7.5 to 10 MHz are typically used for LUS, employing B-mode
      scanning and color Doppler capability on probes with articulating tips. In
      general surgery, LUS has become a common adjunct to the intraoperative staging of
      upper gastrointestinal malignancy to determine resectability, avoiding
      unnecessary laparotomy. In urology, LUS appears to be a promising adjunct for
      four current procedures: difficult pelvic lymphocele marsupialization, renal cyst
      decortication, nephrolithotomy and other renal stone surgery, and cryotherapy of
      renal masses. The role of LUS during varicocelectomy is limited, and enthusiasm
      for this procedure is waning. Laparoscopic ultrasonography is a critical adjunct
      to renal cryoablation, a developmental procedure that currently lacks long-term
      data but is promising as therapy for small, incidentally detected renal masses.
      It appears that as laparoscopic urologic procedures continue to expand, so will
      the application of this promising operative imaging modality.

PMID- 11248926
TI  - New developments in ultrasonography for the detection of prostate cancer.
AB  - The introduction of contrast agents has changed the diagnostic role of
      ultrasonography dramatically. Advanced ultrasound techniques, although currently
      largely unexplored, especially for prostate applications, were introduced to
      improve, for example, differential diagnosis. Also, new technologies became
      available using the interaction of the angioemboli with the transmitted
      ultrasound waves, and sensitive methods to detect microbubbles were developed. As
      the traveling of microbubbles through the vascular system is a dynamic process,
      new information becomes available: when the concentration of the contrast agent
      can be determined as a function of time, a measure for the actual blood flow can
      be obtained that provides quantitative information. Initially developed to
      enhance the ultrasound examinations in cardiac applications, contrast agents can
      currently be found in radiologic applications as well. The first reports of
      enhanced Doppler examinations of prostatic blood flow have been published, and
      the results indicate that contrast agents are a promising addition to the
      conventional ultrasound examination. In this paper, we present a short overview
      of the status of transrectal ultrasound imaging in prostate cancer, background
      information on contrast agents and imaging modalities, and early results of
      enhanced Doppler studies of the prostate to identify cancer. The early results
      suggest the feasibility of using angioemboli to enhance ultrasound imaging of
      prostate diseases, and although many issues remain to be solved, angioemboli in
      combination with a dedicated imaging modality have the potential to improve the
      diagnostic application of ultrasound in evaluating the prostate for disease.

PMID- 11248927
TI  - Effects of attention and unilateral neglect on auditory stream segregation.
AB  - Two pairs of experiments studied the effects of attention and of unilateral
      neglect on auditory streaming. The first pair showed that the build up of
      auditory streaming in normal participants is greatly reduced or absent when they
      attend to a competing task in the contralateral ear. It was concluded that the
      effective build up of streaming depends on attention. The second pair showed that
      patients with an attentional deficit toward the left side of space (unilateral
      neglect) show less stream segregation of tone sequences presented to their left
      than to their right ears. Streaming in their right ears was similar to that for
      stimuli presented to either ear of healthy and of brain-damaged controls, who
      showed no across-ear asymmetry. This result is consistent with an effect of
      attention on streaming, constrains the neural sites involved, and reveals a
      qualitative difference between the perception of left- and right-sided sounds by
      neglect patients.

PMID- 11248928
TI  - Illusory conjunctions of pitch and duration in unfamiliar tone sequences.
AB  - In 3 experiments, the authors examined short-term memory for pitch and duration
      in unfamiliar tone sequences. Participants were presented a target sequence
      consisting of 2 tones (Experiment 1) or 7 tones (Experiments 2 and 3) and then a
      probe tone. Participants indicated whether the probe tone matched 1 of the target
      tones in both pitch and duration. Error rates were relatively low if the probe
      tone matched 1 of the target tones or if it differed from target tones in pitch,
      duration, or both. Error rates were remarkably high, however, if the probe tone
      combined the pitch of 1 target tone with the duration of a different target tone.
      The results suggest that illusory conjunctions of these dimensions frequently
      occur. A mathematical model is presented that accounts for the relative
      contribution of pitch errors, duration errors, and illusory conjunctions of pitch
      and duration.

PMID- 11248929
TI  - Active control of locomotion facilitates nonvisual navigation.
AB  - In some navigation tasks, participants are more accurate if they view the
      environment beforehand. To characterize the benefits associated with visual
      previews, 32 blindfolded participants were guided along simple paths and asked to
      walk unassisted to a specified destination (e.g., the origin). Paths were
      completed without vision, with or without a visual preview of the environment.
      Previews did not necessarily improve nonvisual navigation. When previewed
      landmarks stood near the origin or at off-path locations, they provided little
      benefit; by contrast, when they specified intermediate destinations (thereby
      increasing the degree of active control), performance was greatly enhanced. The
      results suggest that the benefit of a visual preview stems from the information
      it supplies for actively controlled locomotion. Accuracy in reaching the final
      destination, however, is strongly contingent upon the destination's location
      during the preview.

PMID- 11248930
TI  - Congruity effects evoked by subliminally presented primes: automaticity rather
      than semantic processing.
AB  - In a size judgment task on words denoting concrete objects, subliminally
      presented stimuli that preceded the targets influenced response times and were
      dependent on whether responses to the prime and the target were congruent or
      incongruent (Experiment 1). These findings, mirroring S. Dehaene et al. (1998),
      imply that primes are unconsciously categorized and processed to the response
      stage. However, the effect does not generalize to primes that are not in the
      response set (Experiment 2), and even exposure to primes not in the response set
      in an interleaved naming-size judgment task fails to induce it (Experiment 3).
      However, the effect generalizes from lowercase primes to the same set of
      uppercase targets (Experiment 4), suggesting an abstract level of operation. The
      findings suggest that rather than resulting from unconscious prime
      categorization, the congruity effect results from automatized stimulus-response
      mappings. Potential differences between the number and the word domain are
      discussed.

PMID- 11248931
TI  - Perception of /r/ and /l/ in a stop cluster: evidence of cross-modal context
      effects.
AB  - Experiments were conducted investigating unimodal and cross-modal phonetic
      context effects on /r/ and /l/ identifications to test a hypothesis that context
      effects arise in early auditory speech processing. Experiment 1 demonstrated an
      influence of a preceding bilabial stop consonant on the acoustic realization of
      /r/ and /l/ produced within the stop clusters /ibri/ and /ibli/. In Experiment 2,
      members of an acoustic /iri/ to /ili/ continuum were paired with an acoustic
      /ibi/. These dichotic tokens were associated with an increase in "l"
      identification relative to the /iri/ to /ili/ continuum. In Experiment 3, the
      /iri/ to /ili/ tokens were dubbed onto a video of a talker saying /ibi/. This
      condition was associated with a reliable perceptual shift relative to an auditory
      only condition in which the /iri/ to /ili/ tokens were presented by themselves,
      ruling out an account of these context effects as arising during early auditory
      processing.

PMID- 11248932
TI  - Preconstancy information can influence visual search: the case of lightness
      constancy.
AB  - Can visual search be based on preconstancy representations of the scene--that is,
      ones in which accidental characteristics of the scene, such as shadows, point of
      view, and distance, have not yet been discounted? This question was addressed
      within the specific context of lightness constancy, the phenomenon that surface
      lightness is perceived as relatively unchanged despite changes in illumination
      conditions. Three experiments yielded evidence of preconstancy influence on
      visual search. This was true even when the preconstancy information that seemed
      to influence search was unavailable at a reportable level. The results suggest
      that visual search processes can be engaged before the processing that leads to
      the experienced perception of the scene is complete.

PMID- 11248933
TI  - Dissociation between activation and attention effects in time estimation:
      implications for internal clock models.
AB  - In a time production task, the participants' activation level and attention
      devoted to time were manipulated respectively by means of click trains delivered
      at 2 different intensities during the task and by introducing a concurrent
      reaction time task. Activation level is classically considered to affect the rate
      of an internal pacemaker, whereas the way attention affects time estimation is a
      matter of debate. Three models that differ as to the effect of attention were
      evaluated. Predictions on the interaction pattern between activation and
      attention were derived for each of the 3 models. When manipulated jointly, these
      2 factors proved to be independent, as they had additive effects on the
      performance. This finding suggests that the activation level affects the
      pacemaker rate, whereas the attention level affects an accumulation process by
      directly acting on a switch functioning in an all-or-none fashion.

PMID- 11248934
TI  - The tilt-constancy theory of visual illusions.
AB  - The authors argue that changes in the perception of vertical and horizontal
      caused by local visual cues can account for many classical visual illusions.
      Because the perception of orientation is influenced more by visual cues than
      gravity-based cues when the observer is tilted (e.g., S. E. Asch & H. A. Witkin,
      1948), the authors predicted that the strength of many visual illusions would
      increase when observers were tilted 30 degrees. The magnitude of Zollner,
      Poggendorff, and Ponzo illusions and the tilt-induction effect substantially
      increased when observers were tilted. In contrast, the Muller-Lyer illusion and a
      size constancy illusion, which are not related to orientation perception, were
      not affected by body orientation. Other theoretical approaches do not predict the
      obtained pattern of results.

PMID- 11248935
TI  - Grasping objects by their handles: a necessary interaction between cognition and
      action.
AB  - Research has illustrated dissociations between "cognitive" and "action" systems,
      suggesting that different representations may underlie phenomenal experience and
      visuomotor behavior. However, these systems also interact. The present studies
      show a necessary interaction when semantic processing of an object is required
      for an appropriate action. Experiment 1 demonstrated that a semantic task
      interfered with grasping objects appropriately by their handles, but a
      visuospatial task did not. Experiment 2 assessed performance on a visuomotor task
      that had no semantic component and showed a reversal of the effects of the
      concurrent tasks. In Experiment 3, variations on concurrent word tasks suggested
      that retrieval of semantic information was necessary for appropriate grasping. In
      all, without semantic processing, the visuomotor system can direct the effective
      grasp of an object, but not in a manner that is appropriate for its use.

PMID- 11248936
TI  - Effects of number and strength of competing solutions on the perceptual
      interference effect.
AB  - Five-letter fragments of recently studied 8-letter words are easier to solve when
      presented all at once than when clarified from a more degraded form (i.e., by
      starting with a 2-letter fragment and adding letters). The competition
      explanation proposes that highly degraded stimuli activate alternative hypotheses
      that interfere with target identification. In Experiment 1, the number of
      solutions that fit the initial, 2-letter fragment was varied. Performance was
      better in the 2-solution than in the 1-solution condition. In Experiment 2,
      distractor solutions (solutions that fit the 2-letter fragment but not subsequent
      fragments) were either primed (previously studied) or unprimed. Solution
      performance was better when distractors were primed rather than unprimed.
      Perceptual interference appears to result from negative feedback operating on a
      prematurely activated correct hypothesis, rather than from competition between
      hypotheses.

PMID- 11248937
TI  - Effect anticipation and action control.
AB  - According to the authors' 2-phase model of action control, people first
      incidentally acquire bidirectional associations between motor patterns and
      movement-contingent events and then intentionally use these associations for goal
      directed action. The authors tested the model in 4 experiments, each comprising
      an acquisition phase, in which participants experienced co-occurrences between
      left and right keypresses and low- and high-pitched tones, and a test phase, in
      which the tones preceded the responses in forced- and free-choice designs. Both
      reaction time and response frequency in the test phase depended on the learned
      associations, indicating that presenting a tone activated the associated
      response. Results are interpreted as evidence for automatic action-outcome
      integration and automatic response priming through learned action effects. These
      processes may be basic for the control of voluntary action by the anticipation of
      action goals.

PMID- 11248939
TI  - Dissociation of muscular and spatial constraints on patterns of interlimb
      coordination.
AB  - Interlimb coordination is subject to constraints. One major constraint has been
      described as a tendency for homologous muscle groups to be activated
      simultaneously. Another has been described as a biasing of limb segments to
      movement in the same direction. In 2 experiments, the 2 constraints were placed
      in opposition: In-phase or antiphase contraction of homologous muscles of
      contralateral limbs produced movement that was spatially antiphase or in-phase,
      respectively. Probability distributions of relative phase were obtained under
      manipulations of phase detuning and movement speed. They revealed that the
      equilibrium and stability of coordination were related, respectively, to spatial
      relative phase and muscular relative phase. Previously observed spatial and
      muscular constraints reflect a (possibly very general) factorization of attractor
      location and attractor strength in the dynamics of interlimb coordination.

PMID- 11248938
TI  - Why practice reduces dual-task interference.
AB  - M. A. Van Selst, E. Ruthruff, and J. C. Johnston (1999) found that practice
      dramatically reduced dual-task interference in a Psychological Refractory Period
      (PRP) paradigm with 1 vocal response and 1 manual response. Results from 3
      further experiments using the highly trained participants of M. A. Van Selst et
      al. (1999) support 4 main conclusions: (a) A processing bottleneck exists even
      after extensive practice; (b) the principal cause of the reduction in PRP
      interference with practice is shortening of Task 1 bottleneck stages; (c) a
      secondary cause is that 1 or more, but not all, of the Task 2 substages that are
      postponed before practice are not postponed after practice (i.e., become
      automatized); and (d) the extent of PRP reduction with practice depends on the
      modalities of the 2 responses. A control experiment with 2 manual response tasks
      showed less PRP reduction with practice than that found by Van Selst et al.

PMID- 11248940
TI  - Movement prediction and movement production.
AB  - The prediction of future positions of moving objects occurs in cases of actively
      produced and passively observed movement. Additionally, the moving object may or
      may not be tracked with the eyes. The authors studied the difference between
      active and passive movement prediction by asking observers to estimate
      displacements of an occluded moving target, where the movement was driven by the
      observer's manual action or was passively observed. In the absence of eye
      tracking, they found that in the active condition, estimates are more
      anticipatory than in the passive conditions. Decreasing the congruence between
      motor action and visual feedback diminished but did not eliminate the
      anticipatory effect of action. When the target was tracked with the eyes, the
      effect of manual action disappeared. Results indicate distinct contributions of
      hand and eye movement signals to the prediction of trajectories of moving
      objects.

PMID- 11248941
TI  - Location and frequency cues in auditory selective attention.
AB  - The roles of frequency and location cues in auditory selective attention were
      investigated in a series of experiments in which target tones were distinguished
      from distractors by frequency, location, or the conjunction of frequency and
      location features. When frequency separations in high-rate tone sequences were
      greater than 1 octave, participants were fastest at identifying targets defined
      by frequency and were sometimes faster at identifying conjunction than location
      targets. Frequency salience diminished as filtering demands were reduced: At long
      interstimulus intervals (> 2.0 s), performance was superior in location
      conditions. The results suggest that frequency may play a role in auditory
      selective attention tasks analogous to the role of spatial position in visual
      attention.

PMID- 11248942
TI  - Influence of prime-probe stimulus onset asynchrony and prime precuing
      manipulations on semantic priming effects with words in a lexical-decision task.
AB  - The present research examines semantic priming from attended and unattended
      parafoveal words. Participants made a lexical decision in response to a single
      central target. The target was preceded by two parafoveal prime words, with one
      of them (the attended prime) being precued by a peripheral cue. The main
      variables manipulated across experiments were cue informativeness (valid vs.
      neutral cues) and stimulus onset asynchrony (SOA) between prime and probe (200,
      300, 600, or 1,000 ms). The results showed (a) reliable semantic priming from
      both attended and ignored prime words and (b) that the ignored priming effects
      were either negative or positive, depending on both the prime-probe SOA and cue
      informativeness. The present findings are discussed in relation to inhibitory
      versus episodic retrieval models of negative priming.

PMID- 11248943
TI  - Storage of features, conjunctions and objects in visual working memory.
AB  - Working memory can be divided into separate subsystems for verbal and visual
      information. Although the verbal system has been well characterized, the storage
      capacity of visual working memory has not yet been established for simple
      features or for conjunctions of features. The authors demonstrate that it is
      possible to retain information about only 3-4 colors or orientations in visual
      working memory at one time. Observers are also able to retain both the color and
      the orientation of 3-4 objects, indicating that visual working memory stores
      integrated objects rather than individual features. Indeed, objects defined by a
      conjunction of four features can be retained in working memory just as well as
      single-feature objects, allowing many individual features to be retained when
      distributed across a small number of objects. Thus, the capacity of visual
      working memory must be understood in terms of integrated objects rather than
      individual features.

PMID- 11248944
TI  - Reinforcement-driven dimensionality reduction--a model for information processing
      in the basal ganglia.
AB  - Although anatomical studies of the basal ganglia show the existence of extensive
      convergence and lateral inhibitory connections, physiological studies failed to
      show correlated neural activity or lateral interaction in these nuclei. These
      seemingly contradictory results could be explained with a model in which the
      basal ganglia reduce the dimensionality of cortical information using optimal
      extraction methods. Simulations of this model predict a transient change in the
      efficacy of the feed-forward and lateral synapses following changes in
      reinforcement signal, causing an increase in correlated firing rates. This
      process ultimately restores the steady-state situation with diminished efficacy
      of lateral inhibition and no correlation of firing. Our experimental results
      confirm the model's predictions: rate correlations show a drastic decrease
      between the input stage (cortex) and output stage (pallidum). Moreover,
      preliminary analysis revealed that pallidal correlations show a transient
      increase following discrepancies between the animal's predictions and reality. We
      therefore propose that by using a reinforcement-driven dimensionality reduction
      process the basal ganglia achieve efficient extraction of cortical salient
      information that may then be used by the frontal cortex for execution and
      planning of forthcoming actions.

PMID- 11248945
TI  - Electrical coupling in smooth muscles. Is it universal?
AB  - There is strong experimental evidence for electrical coupling in all types of
      smooth muscle. In some publications, and particularly in physiological textbooks,
      smooth muscles are still divided into those that are electrically coupled and
      those that are not. In this article we review the evidence for the universal
      presence of coupling in smooth muscles and the underlying mechanism, which, in
      most cases, appears to be gap junctions. We propose a classification of smooth
      muscles based on the mechanisms that initiate their activity. The two main types
      of smooth muscle according to this classification are neurogenic (e.g., iris,
      arterioles, vas deferens) and myogenic (e.g., urinary bladder, intestine, most
      blood vessels).

PMID- 11248946
TI  - Intracellular calcium dynamics--sparks of insight.
AB  - Calcium ions are of key importance in a large number of cellular functions. In
      the past decade a large variety of cells have been found to show localized
      increases in the intracellular calcium concentration named calcium sparks. In
      this brief review, the methodology of detecting calcium sparks by confocal
      microscopy is summarized. Some of the properties of calcium sparks in muscle
      (cardiac, skeletal and smooth muscles), neurons, nerve terminals and oocytes
      aredescribed. Speculations are put forward regarding their possible role in
      microcontrol of cell function.

PMID- 11248947
TI  - Basic and clinical physiology of the inner ear receptors and their neural
      pathways in the brain.
AB  - The six receptors of the inner ear (cochlea, two otolith organs and three
      semicircular canals) share a common transduction unit made up of a sensory hair
      cell, a first order sensory neuron and the synapse between them. Displacement of
      the stereocilia in a particular direction leads to excitation of the hair cell
      and activation of the neuron. Electrical and mechanical reflections of these
      stages of transduction can be recorded non-invasively in humans and in animals.
      These include cochlear microphonic potentials, otoacoustic emissions, auditory
      and vestibular evoked potentials. The ability to record these activities can be
      used to track the development of inner ear function in the fetus and neonate and
      to study the effects of various ototoxic agents (e.g. noise) and drugs.

PMID- 11248948
TI  - The mood cycle hypothesis: possible involvement of steroid hormones in mood
      regulation by means of Na+, K+-ATPase inhibition.
AB  - The mood cycle hypothesis attempts to propose a model for mood regulation based
      on current data. The hypothesis contends that steroid hormones inhibit sodium
      potassium adenosine triphosphatase (Na+, K+-ATPase; Na+ pump) in the
      hypothalamus, either directly or by converting into digitalis-like compounds.
      This inhibition stimulates beta-endorphin (beta-E) secretion, which is normally
      construed as elevated mood. In turn, beta-E inhibits steroid secretion, thus
      completing negative feedback loops. These loops are collectively termed the mood
      cycle.

PMID- 11248949
TI  - Exertional heat stroke--the prevention of a medical emergency.
AB  - In most cases, exertional heat stroke (EHS) can be prevented in the military
      setting. The actions taken by the Israel Defense Forces (IDF) and their outcome
      prove this well. Unfortunately, despite the available information, there are
      still incidents of failure of command in conducting physical exercise, leading to
      EHS. In our experience, most incidences are a consequence of disregarding safety
      regulations. The application of simple and reasonable measures will not only
      prevent accidents from happening, but will also result in better trained
      soldiers.

PMID- 11248950
TI  - Stress evaluation by the physiological strain index (PSI).
AB  - A physiological strain index (PSI) based on rectal temperature (Tre) and heart
      rate was recently suggested to evaluate exercise/heat stress. This review
      summarizes the development of PSI which was evaluated from seven different
      databases during the last three years. PSI was developed from data obtained from
      man performing exercise in the heat and from a separate database of man wearing
      protective clothing and exercising in hot-dry and hot-wet environmental
      conditions. This index was also evaluated for heat strain associated with
      hypohydration and for exercise/heat stress and gender. In addition, PSI was
      adjusted for values in rats, and could be used to assess the individual roles
      played by heat acclimation and exercise training in rats. This simple to use
      index scales strain to a range of 0-10, can be used on-line or during data
      analysis, and includes the ability to depict rest and recovery periods. The PSI
      has the potential to be widely accepted and to serve universally.

PMID- 11248951
TI  - Excitation and propagation of non-axisymmetric guided waves in a hollow cylinder.
AB  - Excitation and propagation of non-axisymmetric guided waves in a hollow cylinder
      is studied by using the normal mode expansion method (NME). Different sources
      such as angle beam, tube end excitation with normal beam, and comb transducer
      possibilities are discussed based on the derivations of the NME method. Numerical
      calculations are focused on the case of angle beam partial loading. Based on the
      NME method, the amplitude coefficients for all of the harmonic modes are
      obtained. Due to the difference of phase velocities for different modes, the
      superimposed total field varies with propagating distances and hence makes
      particle displacement distribution patterns (angular profile) change with
      distance. This varying non-axisymmetric angular profile of guided waves
      represents a nonuniform energy distribution around the hollow cylinder and thus
      has an impact on the inspection ability of guided waves. The angular profiles of
      an angle beam source are predicted by theory and then verified by experiments.
      The predicted angular profiles also provide information for determining the
      transducer location to find defects in a certain position on the hollow cylinder.

PMID- 11248952
TI  - Least-squares Legendre spectral element solutions to sound propagation problems.
AB  - This paper presents a novel algorithm and numerical results of sound wave
      propagation. The method is based on a least-squares Legendre spectral element
      approach for spatial discretization and the Crank-Nicolson [Proc. Cambridge
      Philos. Soc. 43, 50-67 (1947)] and Adams-Bashforth [D. Gottlieb and S. A. Orszag,
      Numerical Analysis of Spectral Methods: Theory and Applications (CBMS-NSF
      Monograph, Siam 1977)] schemes for temporal discretization to solve the
      linearized acoustic field equations for sound propagation. Two types of NASA
      Computational Aeroacoustics (CAA) Workshop benchmark problems [ICASE/LaRC
      Workshop on Benchmark Problems in Computational Aeroacoustics, edited by J. C.
      Hardin, J. R. Ristorcelli, and C. K. W. Tam, NASA Conference Publication 3300,
      1995a] are considered: a narrow Gaussian sound wave propagating in a one
      dimensional space without flows, and the reflection of a two-dimensional acoustic
      pulse off a rigid wall in the presence of a uniform flow of Mach 0.5 in a semi
      infinite space. The first problem was used to examine the numerical dispersion
      and dissipation characteristics of the proposed algorithm. The second problem was
      to demonstrate the capability of the algorithm in treating sound propagation in a
      flow. Comparisons were made of the computed results with analytical results and
      results obtained by other methods. It is shown that all results computed by the
      present method are in good agreement with the analytical solutions and results of
      the first problem agree very well with those predicted by other schemes.

PMID- 11248953
TI  - Improved solution for the vortical and acoustical mode coupling inside a two
      dimensional cavity with porous walls.
AB  - This work presents an improved solution to a former study that analyzes the
      oscillatory motion of gases prescribed by vortico-acoustical mode coupling inside
      a two-dimensional porous cavity. The physical problem arises in the context of an
      oscillating gas inside a rectangular enclosure with wall transpiration,
      sublimation, or sweating. Previously, a multiple-scale solution was derived for
      the temporal field. The asymptotic formulation was based on an unconventional
      choice of scales. Its accuracy was also commensurate with the size of epsilon, a
      parameter that captured the effect of small viscosity. Currently, an exact
      solution is derived and compared to the previous formulation. A simple WKBJ
      solution is also constructed for validation purposes. Unlike both asymptotic
      formulations, the exact solution remains accurate regardless of the range of
      physical parameters.

PMID- 11248954
TI  - Fundamental azimuthal modes of a constricted annular resonator: theory and
      measurement.
AB  - The fundamental azimuthal modes of a constricted annular resonator are
      investigated. It is found that a given mode of an unconstricted resonator splits
      into two separate modes in the constricted resonator. One mode is of a higher
      frequency and has a pressure antinode centered in the constricted region. The
      other mode is of a lower frequency and has a pressure node centered in the
      constricted region. The resonance frequency of the higher-frequency modes
      increases linearly with a decrease in the constricted to unconstricted area
      ratio, whereas the lower frequency drops nonlinearly. Measurements and theory
      match to within 0.5% when end corrections and thermo-viscous losses are included
      in the system model. It was found that end correction impedances derived by mode
      matching techniques were the only ones accurate enough to match the measurements
      and computation to within the error bounds.

PMID- 11248955
TI  - Second-harmonic generation in sound beams reflected from, and transmitted
      through, immersed elastic solids.
AB  - Second-harmonic generation in sound beams reflected from and transmitted through
      thick isotropic elastic solids is investigated experimentally. Measurements of
      diffraction patterns are compared with a theoretical model based on integral
      solutions for harmonic generation in sound beams. The solutions are connected by
      classical linear theory for reflection and transmission at fluid-solid
      interfaces. Nonspecular phenomena associated with rapid phase variations near
      critical angles are accurately described. The principal restriction is that the
      solid is sufficiently thick that internal reflections may be ignored.

PMID- 11248956
TI  - Observation of nonlinear acoustic effects at isotropic solid-solid interfaces.
AB  - The second harmonic generation of SV shear waves at isotropic solid-solid
      interfaces is experimentally studied. The amplitude of shear waves is measured
      for the interfaces of glass-air, glass-iron, glass-copper, and glass-aluminum.
      The measured angular relation of amplitude of the second harmonic wave is
      compared with theory and the agreement is reasonably good. The influence of the
      physical state of the interface on second harmonic generation is also observed.
      It is found that the second harmonic generation is sensitive to the interface
      state.

PMID- 11248957
TI  - Scattering from a partially fluid-filled, elastic-shelled sphere.
AB  - In this article a sphere is taken to be partially filled with fluid so that its
      interior is part fluid and part air. A set of basis of functions, based upon an
      origin at the fluid/air interface, is used for the interior and a set of basis
      functions based upon the center of the sphere is used for the shell and exterior
      of the sphere. These sets of basis functions are coupled at the shell/interior
      interface and the resulting coupled system of equations solved to yield the
      scattered field. Numerical computations using this approach are presented for
      varying amounts of fluid-fill and for varying incident plane waves.

PMID- 11248958
TI  - An evaluation of the accuracy of shallow water matched field inversion results.
AB  - In this article the accuracy of geo-acoustic and geometric parameter estimates
      obtained through matched field inversion (MFI) was assessed. Multi-frequency MFI
      was applied to multi-tone data (200-600 Hz) received at a 2-km source/receiver
      range. The acoustic source was fixed and the signals were received at a vertical
      array. Simultaneously with the acoustic transmissions, a CTD (conductivity,
      temperature and depth)-chain was towed along the acoustic track. A genetic
      algorithm was used for the global optimization, whereas a normal mode model was
      applied for the forward acoustic calculations. Acoustic data received at
      consecutive times were inverted and the stability of the inverted parameters was
      determined. Also, the parameter estimates were compared with independent
      measurements, such as multi-channel seismic surveys (for geo-acoustic
      parameters). The obtained uncertainty in the inversion results was assumed to
      have two distinct origins. The first origin is the inversion method itself, since
      each optimization will come up with some solution close to the exact optimum.
      Parameter coupling and the fact that some parameters hardly influence the
      acoustic propagation further contribute to this uncertainty. The second is due to
      oceanographic variability. Both contributions were evaluated through simulation.
      The contribution of oceanographic variability was evaluated through synthetic
      inversions that account for the actual sound speed variations as measured by the
      towed CTD-chain.

PMID- 11248959
TI  - The intensity coherence function of time for partially saturated acoustic
      propagation through ocean internal waves.
AB  - The intensity coherence function of time for partially saturated acoustic
      propagation through internal waves is calculated with a method that is improved
      over previous treatments. Two specific improvements are introduced: the usual
      expansion in (1/lambdaphi2) is carried out to a higher order, and then the terms
      of that expansion are calculated with a new perturbative method. The method is
      applied to propagation without a sound channel, for both phase-screen and
      continuous-medium cases. The validity of the new perturbative method is estimated
      by calculating the next order error terms. Accuracies at the few-percent level
      are found. The new analytic formulas are also corroborated with numerical
      integration. Finally, the method is applied to a specific ocean-acoustic
      experiment [Azores Fixed Acoustic Range (AFAR)]. In order to achieve good
      agreement with experiment it will be necessary to add an accurate treatment of
      the sound channel to the present perturbation method.

PMID- 11248960
TI  - Time-reversing array retrofocusing in noisy environments.
AB  - Acoustic time reversal is a robust means of retrofocusing acoustic energy, in
      both time and space, to the original sound-source location. However, noise may
      limit the performance of a time-reversing array (TRA) at long source-array
      ranges, or when the original-source or TRA-element power levels are low. The
      operation of a TRA requires two steps (reception and transmission) so both TRA
      broadcast noise and ambient noise must be taken into account. In this paper,
      predictions are made for how a simple omnidirectional noise field influences the
      probability that the signal amplitude from a narrow-band TRA will exceed the
      noise at the TRA's retrofocus. A general formulation for the probability of TRA
      retrofocusing, which can be used for TRA design, is developed that includes: the
      variance of the noise field, the original source strength, the TRA's element
      output power, the number of TRA elements (N), and the propagation characteristics
      of the environment. This formulation predicts that a TRA's array gain (in dB) at
      the retrofocus may be as high as + 10log10(N) to + 20 log10(N) depending on the
      relative strengths of the original source and the TRA's elements. Monte Carlo
      simulations in both a free-space environment and a shallow-ocean sound-channel
      environment compare well to this probability formulation even when simple
      approximate parametric relationships for the appropriate Green's functions are
      used. The dominant deviation between theory and simulation in the sound channel
      is caused by acoustic absorption.

PMID- 11248961
TI  - Noncontact quantitative spatial mapping of stress and flexural rigidity in thin
      membranes using a picosecond transient grating photoacoustic technique.
AB  - This paper describes a purely optical technique for measuring and spatially
      mapping out stress and rigidity in thin membranes. Its application to a membrane
      of aluminum nitride that has significant spatial nonuniformities in its elastic
      properties demonstrates the method. The attractive features of this technique-
      fast, noncontacting measurement, good spatial resolution, ability to quantify in
      plane anisotropy--make it potentially useful for characterizing elements of
      microelectromechanical structures, masks for advanced lithography systems,
      acoustic filters, and other devices in which the mechanical properties of
      membranes are important.

PMID- 11248962
TI  - Bender transducer design and operation.
AB  - An empirical study covering a wide range of bender transducer sizes and operating
      frequencies is reported. A spherical device model is shown to give good account
      of bender performance, including interaction effects. A set of empirical rules
      for scaling equivalent circuit parameters according to the device geometry is
      identified. An effective spherical radius, approximately half the diaphragm
      radius, is identified for the typical bender. The effects of pressure and drive
      voltage on performance are described for particular devices. Sensitivity factors
      for the equivalent circuit parameters to the operating conditions are determined.
      These are related to sensitivity factors for the coupling coefficient (Kc) and
      electromechanical transformer turns ratio (N). Both these parameters are shown to
      have similar sensitivity responses, decreasing with pressure (planar stress), and
      increasing with voltage (electric field). The results of high drive tests carried
      out at Seneca Lake are reported. Values of conventional figures of merit (FOM(V)
      and FOM(M)), close to the highest claimed for any underwater transducer, are
      tabled. When allowance for the operating efficiency is included in the figure of
      merit definitions, the bender appears to be superior to other device types.

PMID- 11248963
TI  - Estimation of broadband acoustic power due to rib forces on a reinforced panel
      under turbulent boundary layer-like pressure excitation. I. Derivations using
      string model.
AB  - This paper shows that, when the attachment forces on a rib-reinforced panel
      subjected to turbulent boundary layer (TBL) excitation can be considered to
      radiate independently, the rib-related acoustic power in a broad (e.g., one-third
      octave) frequency band can be estimated as the product of the average mean
      squared force, the real part of the radiation admittance of an attachment force,
      and the number of ribs. Using a simple model of a string with point mass or
      spring attachments, an approach is developed for estimating the average mean
      squared force in broad frequency bands. The results are in a form that can be
      applied to ribbed plates and shells. The following paper establishes the
      condition under which the ribs can be considered to radiate independently, and
      presents the results of validating calculations for steel plates in water.

PMID- 11248964
TI  - Estimation of broadband acoustic power due to rib forces on a reinforced panel
      under turbulent boundary layer-like pressure excitation. II. Applicability and
      validation.
AB  - The previous paper showed that, when the attachment forces on a rib-reinforced
      panel subjected to turbulent boundary layer excitation can be considered to
      radiate independently, the rib-related acoustic power in a broad (e.g., one-third
      octave) frequency band can be estimated as the product of the average mean
      squared force, the real part of the radiation admittance of an attachment force,
      and the number of ribs. This paper shows that the radiation condition is always
      approximated when the acoustic wavelength is less than twice the rib spacing of a
      periodically reinforced panel, and generally applies at lower frequencies where
      the acoustic wavelength is less than four times the rib spacing. The procedure is
      used to estimate the broadband acoustic power radiated per rib of an infinite
      periodically reinforced membrane and plate in water, and the results are shown to
      agree with those of "exact" calculations.

PMID- 11248965
TI  - Behavior of first guided wave on finite cylindrical shells of various lengths:
      experimental investigation.
AB  - Acoustic backscattering from elastic cylindrical shells of finite lengths,
      immersed in water, is investigated. These objects, characterized by the ratio of
      length over diameter (L/2a = 9.76, 4.88, 2.44, a: outer radius), are excited by
      an obliquely incident plane acoustic wave. In the three cases studied here, the
      radii ratio b/a (b: inner radius) is fixed at 0.97. The investigated
      dimensionless frequency range extends over 10 k1a < or = 50 (k1 : wave number in
      water). The first guided wave, T0, is of particular interest here. The influence
      of the shell's length on the backscattered pressure is experimentally observed in
      the time-angle and frequency-angle representations. In support of this
      experimental study, a time-domain representation is used by extending a
      theoretical model that provides a geometrical description of the helical
      propagation of the surface waves around the shell [Bao, J. Acoust. Soc. Am. 94,
      1461-1466 (1993)]. Theoretical results on cylindrical shells considered as
      infinitely long, with identical characteristics, are compared with both
      experimental representations.

PMID- 11248966
TI  - Incorporation of loudness measures in active noise control.
AB  - An attempt has been made to use a modified version of a standard active noise
      control algorithm in order to take into account the unique response of the human
      auditory system. It has been shown in the past that decreasing the sound pressure
      level at a location does not guarantee a similar decrease in the perceived
      loudness at that location. Typically, active noise control is based on minimizing
      the "error signal" from a mechanical device such as a microphone, whose response
      is nominally flat across the frequency response range of the human ear. However,
      if the response of the ear can be approximated by digitally filtering the error
      signal before it reaches the adaptive controller, one can, in effect, minimize
      the more subjective loudness level, as opposed to the sound pressure level. The
      work reported here entails simulating active noise control based upon minimizing
      perceived loudness for a collection of input noise signals. A comparison of the
      loudness of the resulting error signal is made to the loudness of that resulting
      from standard sound pressure level minimization. It has been found that the
      effectiveness of this technique is largely dependent upon the nature of the input
      noise signal. Furthermore, this technique is judged to be worth considering for
      use with applications of active noise control where the uncontrolled noise more
      prominently constitutes low range audio frequencies (approximately 30 Hz-100 Hz)
      than medium range audio frequencies (approximately 300 Hz-600 Hz).

PMID- 11248967
TI  - Computation of edge diffraction for more accurate room acoustics auralization.
AB  - Inaccuracies in computation and auralization of room impulse responses are
      related in part to inadequate modeling of edge diffraction, i.e., the scattering
      from edges of finite surfaces. A validated time-domain model (based on analytical
      extensions to the Biot-Tolstoy-Medwin technique) is thus employed here to compute
      early room impulse responses with edge diffraction. Furthermore, the computations
      are extended to include combinations of specular and diffracted paths in the
      example problem of a stage-house. These combinations constitute a significant
      component of the total nonspecular scattering and also help to identify edge
      diffraction in measured impulse responses. The computed impulse responses are
      then convolved with anechoic signals with a variety of time-frequency
      characteristics. Initial listening tests with varying orders and combinations of
      diffraction suggest that (1) depending on the input signal, the diffraction
      contributions can be clearly audible even in nonshadow zones for this
      conservative open geometry and (2) second-order diffraction to nonshadowed
      receivers can often be neglected. Finally, a practical implementation for
      binaural simulation is proposed, based on the singular behavior of edge
      diffraction along the least-time path for a given source-edge-receiver
      orientation. This study thus provides a first major step toward computing edge
      diffraction for more accurate room acoustics auralization.

PMID- 11248968
TI  - Determination of the complex Young and shear dynamic moduli of viscoelastic
      materials.
AB  - The Young and shear dynamic moduli of viscoelastic materials are determined from
      laser vibrometric measurements of the surface motion of a three-dimensional
      sample excited by a piezoelectric actuator inside a chamber with controllable
      temperature and static pressure. The moduli are estimated from an inversion code
      that minimizes the difference between the data and the predictions from a finite
      element model in which the elastic moduli are the adjustable parameters. The
      technique is first used to measure the dynamic properties of homogeneous samples
      and the results are compared with those obtained by the standard rod resonance
      technique. Results are then obtained with microvoided samples in the 0.5-3 kHz
      frequency range, at temperatures ranging from 7 to 40 degrees C, and static
      pressures ranging from ambient to 34 atm (3.45 MPa or 500 psi). The limitations
      of the technique are discussed.

PMID- 11248969
TI  - Distortion-product source unmixing: a test of the two-mechanism model for DPOAE
      generation.
AB  - This paper tests key predictions of the "two-mechanism model" for the generation
      of distortion-product otoacoustic emissions (DPOAEs). The two-mechanism model
      asserts that lower-sideband DPOAEs constitute a mixture of emissions arising not
      simply from two distinct cochlear locations (as is now well established) but,
      more importantly, by two fundamentally different mechanisms: nonlinear distortion
      induced by the traveling wave and linear coherent reflection off pre-existing
      micromechanical impedance perturbations. The model predicts that (1) DPOAEs
      evoked by frequency-scaled stimuli (e.g., at fixed f2/f1) can be unmixed into
      putative distortion- and reflection-source components with the frequency
      dependence of their phases consistent with the presumed mechanisms of generation;
      (2) The putative reflection-source component of the total DPOAE closely matches
      the reflection-source emission (e.g., low level stimulus-frequency emission)
      measured at the same frequency under similar conditions. These predictions were
      tested by unmixing DPOAEs into components using two completely different methods:
      (a) selective suppression of the putative reflection source using a third tone
      near the distortion-product frequency and (b) spectral smoothing (or,
      equivalently, time-domain windowing). Although the two methods unmix in very
      different ways, they yield similar DPOAE components. The properties of the two
      DPOAE components are consistent with the predictions of the two-mechanism model.

PMID- 11248970
TI  - Spontaneous otoacoustic emissions and relaxation dynamics of long decay time OAEs
      in audiometrically normal and impaired subjects.
AB  - The relationship between hearing loss, detected by measuring the audiometric
      threshold shift, and the presence of long-lasting otoacoustic emissions, has been
      studied in a population of 66 adult males, by analyzing the cochlear response in
      the 80 ms following the subministration of a click stimulus. Most long-lasting
      OAEs are also recognizable as Synchronized Spontaneous OAEs (SSOAEs). The OAE
      characteristic decay times were evaluated according to the model by Sisto and
      Moleti [J. Acoust. Soc. Am. 106, 1893 (1999)]. The starting hypothesis, confirmed
      by the results, is that long decay time and large equilibrium amplitude are both
      manifestations of the effectiveness of the active feedback mechanism. The
      prevalence and frequency distribution of long-lasting OAEs, and of their SSOAE
      subset, have been separately analyzed for normal and impaired ears. No long
      lasting OAE was found within the hearing loss frequency range, but several were
      found in impaired ears outside the hearing loss range, both at lower and higher
      frequencies. This result suggests that the correlation between the presence of
      long-lasting OAEs and good cochlear functionality be local in the frequency
      domain. The monitor of the OAE decay time is proposed as a new possible method
      for early detecting hearing loss in populations exposed to noise.

PMID- 11248971
TI  - A phenomenological model for the responses of auditory-nerve fibers: I. Nonlinear
      tuning with compression and suppression.
AB  - A phenomenological model was developed to describe responses of high-spontaneous
      rate auditory-nerve (AN) fibers, including several nonlinear response properties.
      Level-dependent gain (compression), bandwidth, and phase properties were
      implemented with a control path that varied the gain and bandwidth of tuning in
      the signal-path filter. By making the bandwidth of the control path broad with
      respect to the signal path, the wide frequency range of two-tone suppression was
      included. By making the control-path filter level dependent and tuned to a
      frequency slightly higher than the signal-path filter, other properties of two
      tone suppression were also included. These properties included the asymmetrical
      growth of suppression above and below the characteristic frequency and the
      frequency offset of the suppression tuning curve with respect to the excitatory
      tuning curve. The implementation of this model represents a relatively simple
      phenomenological description of a single mechanism that underlies several
      important nonlinear response properties of AN fibers. The model provides a tool
      for studying the roles of these nonlinearities in the encoding of simple and
      complex sounds in the responses of populations of AN fibers.

PMID- 11248972
TI  - Distinguishing cochlear pathophysiology in 4-aminopyridine and furosemide treated
      ears using a nonlinear systems identification technique.
AB  - To test the adequacy of physiologic indices derived from a third-order polynomial
      model quantifying cochlear mechano-electric transduction (MET), 24 Mongolian
      gerbils were exposed to either 250-mM glucose (control), 150-mM 4-aminopyridine
      (4-AP), or 30-mM furosemide solutions applied to the round window (RW) membrane.
      The cochlear microphonic (CM) was recorded from the RW in response to 68- and 88
      dB SPL Gaussian noise. A nonlinear systems identification technique (NLID)
      provided the frequency-domain parameters and physiologic indices of the
      polynomial model of MET. The control group showed no change in both compound
      action potential (CAP) thresholds and CM. Exposure to 4-AP and furosemide
      resulted in a similar elevation in CAP thresholds and a reduction in CM. However,
      the polynomial model of MET showed different changes. The operating point, slope,
      and symmetry of the MET function, the polynomial model parameters, and related
      nonlinear coherences differed between the experimental groups. It is concluded
      that the NLID technique is sensitive and specific to alterations in the cochlear
      physiology.

PMID- 11248973
TI  - Temporal pitch perception and the binaural system.
AB  - Two experiments examined the relationship between temporal pitch (and, more
      generally, rate) perception and auditory lateralization. Both used dichotic pulse
      trains that were filtered into the same high (3,900-5,400-Hz) frequency region in
      order to eliminate place-of-excitation cues. In experiment 1, a 1-s periodic
      pulse train of rate Fr was presented to one ear, and a pulse train of rate 2Fr
      was presented to the other. In the "synchronous" condition, every other pulse in
      the 2Fr train was simultaneous with a pulse in the opposite ear. In each trial,
      subjects concentrated on one of the two binaural images produced by this mixture:
      they matched its perceived location by adjusting the interaural level difference
      (ILD) of a bandpass noise, and its rate/pitch was then matched by adjusting the
      rate of a regular pulse train. The results showed that at low Fr (e.g., 2 Hz),
      subjects heard two pulse trains of rate Fr, one in the "higher rate" ear, and one
      in the middle of the head. At higher Fr (>25 Hz) subjects heard two pulse trains
      on opposite sides of the midline, with the image on the higher rate side having a
      higher pitch than that on the "lower rate" side. The results were compared to
      those in a control condition, in which the pulses in the two ears were
      asynchronous. This comparison revealed a duplex region at Fr > 25 Hz, where
      across-ear synchrony still affected the perceived locations of the pulse trains,
      but did not affect their pitches. Experiment 2 used a 1.4-s 200-Hz dichotic pulse
      train, whose first 0.7 s contained a constant interaural time difference (ITD),
      after which the sign of the ITD alternated between subsequent pulses. Subjects
      matched the location and then the pitch of the "new" sound that started halfway
      through the pulse train. The matched location became more lateralized with
      increasing ITD, but subjects always matched a pitch near 200 Hz, even though the
      rate of pulses sharing the new ITD was only 100 Hz. It is concluded from both
      experiments that temporal pitch perception is not driven by the output of
      binaural mechanisms.

PMID- 11248974
TI  - Influence of rate of change of frequency on the overall pitch of frequency
      modulated tones.
AB  - The mechanism(s) determining pitch may assign less weight to portions of a sound
      where the frequency is changing rapidly. The present experiments explored the
      possible effect of this on the overall pitch of frequency-modulated sounds. Pitch
      matches were obtained between an adjustable unmodulated sinusoid and a sinusoidal
      carrier that was frequency modulated using a highly asymmetric function with the
      form of a repeating U  or inverted U shaped function. The amplitude was constant
      during the 400-ms presentation time of each stimulus, except for 10-ms raised
      cosine onset and offset ramps. In experiment 1, the carrier level was 50 dB SPL
      and the geometric mean of the instantaneous frequency of the modulated carrier,
      fc, was either 0.5, 1, 2, or 8 kHz. The modulation rate (fm) was 5, 10, or 20 Hz.
      The overall depth (maximum to minimum) of the FM was 8% of fc. For all carrier
      frequencies, the matched frequency was shifted away from the mean carrier
      frequency, downwards for the U shaped function stimuli and upwards for the
      repeated inverted U shaped function stimuli. The shift was typically slightly
      greater than 1% of fc, and did not vary markedly with fc. The effect of fm was
      small, but there was a trend for the shifts to decrease with increasing fm for fc
      = 0.5 kHz and to increase with increasing fm for fc = 2 kHz. In experiment 2, the
      carrier level was reduced to 20 dB SL and matches were obtained only for fc = 2
      kHz. Shifts in matched frequency of about 1% were still observed, but the trend
      for the shifts to increase with increasing fm no longer occurred. In experiment
      3, matches were obtained for a 4-kHz carrier at 50 dB SPL. Shifts of about 1%
      again occurred, which did not vary markedly with fm. The shifts in matched
      frequency observed in all three experiments are not predicted by models based on
      the amplitude- or intensity-weighted average of instantaneous frequency (EWAIF or
      IWAIF). The shifts (and the pitch shifts observed earlier for two-tone complexes
      and for stimuli with simultaneous AM and FM) are consistent with a model based on
      the assumption that the overall pitch of a frequency-modulated sound is
      determined from a weighted average of period estimates, with the weight attached
      to a given estimate being inversely related to the short-term rate of change of
      period and directly related to a compressive function of the amplitude.

PMID- 11248975
TI  - Coding of the fundamental frequency in continuous interleaved sampling processors
      for cochlear implants.
AB  - In this study the perception of the fundamental frequency (F0) of periodic
      stimuli by cochlear implant users is investigated. A widely used speech processor
      is the Continuous Interleaved Sampling (CIS) processor, for which the fundamental
      frequency appears as temporal fluctuations in the envelopes at the output. Three
      experiments with four users of the LAURA (Registered trade mark of Philips
      Hearing Implants, now Cochlear Technology Centre Europe) cochlear implant were
      carried out to examine the influence of the modulation depth of these envelope
      fluctuations on pitch discrimination. In the first experiment, the subjects were
      asked to discriminate between two SAM (sinusoidally amplitude modulated) pulse
      trains on a single electrode channel differing in modulation frequency ( deltaf =
      20%). As expected, the results showed a decrease in the performance for smaller
      modulation depths. Optimal performance was reached for modulation depths between
      20% and 99%, depending on subject, electrode channel, and modulation frequency.
      In the second experiment, the smallest noticeable difference in F0 of synthetic
      vowels was measured for three algorithms that differed in the obtained modulation
      depth at the output: the default CIS strategy, the CIS strategy in which the F0
      fluctuations in the envelope were removed (FLAT CIS), and a third CIS strategy,
      which was especially designed to control and increase the depth of these
      fluctuations (F0 CIS). In general, performance was poorest for the FLAT CIS
      strategy, where changes in F0 are only apparent as changes of the average
      amplitude in the channel outputs. This emphasizes the importance of temporal
      coding of F0 in the speech envelope for pitch perception. No significantly better
      results were obtained for the F0 CIS strategy compared to the default CIS
      strategy, although the latter results in envelope modulation depths at which sub
      optimal scores were obtained in some cases of the first experiment. This
      indicates that less modulation is needed if all channels are stimulated with
      synchronous F0 fluctuations. This hypothesis is confirmed in a third experiment
      where subjects performed significantly better in a pitch discrimination task with
      SAM pulse trains, if three channels were stimulated concurrently, as opposed to
      only one.

PMID- 11248977
TI  - Forward masking: adaptation or integration?
AB  - The aim of this study was to attempt to distinguish between neural adaptation and
      persistence (or temporal integration) as possible explanations of forward
      masking. Thresholds were measured for a sinusoidal signal as a function of signal
      duration for conditions where the delay between the masker offset and the signal
      offset (the offset-offset interval) was fixed. The masker was a 200-ms broadband
      noise, presented at a spectrum level of 40 dB (re: 20 microPa), and the signal
      was a 4-kHz sinusoid, gated with 2-ms ramps. The offset-offset interval was fixed
      at various durations between 4 and 102 ms and signal thresholds were measured for
      a range of signal durations at each interval. A substantial decrease in
      thresholds was observed with increasing duration for signal durations up to about
      20 ms. At short offset-offset intervals, the amount of temporal integration
      exceeded that normally found in quiet. The results were simulated using models of
      temporal integration (the temporal-window model) and adaptation. For both models,
      the inclusion of a peripheral nonlinearity, similar to that observed
      physiologically in studies of the basilar membrane, was essential in producing a
      good fit to the data. Both models were about equally successful in accounting for
      the present data. However, the temporal-window model provided a somewhat better
      account of similar data from a simultaneous-masking experiment, using the same
      parameters. This suggests that the linear, time-invariant properties of the
      temporal-window approach are appropriate for modeling forward masking. Overall
      the results confirm that forward masking can be described in terms of peripheral
      nonlinearity followed by linear temporal integration at higher levels in the
      auditory system. However, the difference in predictions between the adaptation
      and integration models is relatively small, meaning that influence of adaptation
      cannot be ruled out.

PMID- 11248976
TI  - A comparison of threshold estimation methods in children 6-11 years of age.
AB  - Estimating detection threshold for auditory stimuli in children can be
      problematic because of lapses in attention and the time limits usually imposed by
      scheduling restrictions or fatigue. Data reported here were collected to compare
      the stability of threshold estimation procedures in testing children ages 6 to 11
      in a three-alternative, forced-choice paradigm. Stimuli consisted of a 1-kHz
      tonal signal and a Gaussian noise masker, bandpass filtered between 500-2,000 Hz
      and presented at 25-dB spectrum level. The signal was either presented for 400 ms
      in the presence of a continuous masker (simultaneous masking) or for 10 ms just
      prior to a 400-ms masker (backward masking). For each masking paradigm the 79%
      correct threshold was assessed via each of three procedures: 3-down, 1-up
      adaptive staircase (Levitt), maximum likelihood estimation (MLE), and method of
      constant stimuli. Percent correct was measured at the end of the study for a
      signal 10 dB above the previously determined threshold in order to estimate the
      most appropriate psychometric function asymptote for fitting data collected via
      the method of constant stimuli. Both the MLE and Levitt procedures produced
      equally stable threshold estimates for both conditions and age groups. This was
      the case despite considerable variability in backward-masking thresholds.

PMID- 11248978
TI  - Three-dimensional vocal tract imaging and formant structure: varying vocal
      register, pitch, and loudness.
AB  - Although advances in techniques for image acquisition and analysis have
      facilitated the direct measurement of three-dimensional vocal tract air space
      shapes associated with specific speech phonemes, little information is available
      with regard to changes in three-dimensional (3-D) vocal tract shape as a function
      of vocal register, pitch, and loudness. In this study, 3-D images of the vocal
      tract during falsetto and chest register phonations at various pitch and loudness
      conditions were obtained using electron beam computed tomography (EBCT). Detailed
      measurements and differences in vocal tract configuration and formant
      characteristics derived from the eight measured vocal tract shapes are reported.

PMID- 11248979
TI  - Effects of consonant environment on vowel formant patterns.
AB  - A significant body of evidence has accumulated indicating that vowel
      identification is influenced by spectral change patterns. For example, a large
      scale study of vowel formant patterns showed substantial improvements in category
      separability when a pattern classifier was trained on multiple samples of the
      formant pattern rather than a single sample at steady state [J. Hillenbrand et
      al., J. Acoust. Soc. Am. 97, 3099-3111 (1995)]. However, in the earlier study all
      utterances were recorded in a constant /hVd/ environment. The main purpose of the
      present study was to determine whether a close relationship between vowel
      identity and spectral change patterns is maintained when the consonant
      environment is allowed to vary. Recordings were made of six men and six women
      producing eight vowels (see text) in isolation and in CVC syllables. The CVC
      utterances consisted of all combinations of seven initial consonants
      (/h,b,d,g,p,t,k/) and six final consonants (/b,d,g,p,t,k/). Formant frequencies
      for F1-F3 were measured every 5 ms during the vowel using an interactive editing
      tool. Results showed highly significant effects of phonetic environment. As with
      an earlier study of this type, particularly large shifts in formant patterns were
      seen for rounded vowels in alveolar environments [K. Stevens and A. House, J.
      Speech Hear. Res. 6, 111-128 (1963)]. Despite these context effects, substantial
      improvements in category separability were observed when a pattern classifier
      incorporated spectral change information. Modeling work showed that many aspects
      of listener behavior could be accounted for by a fairly simple pattern classifier
      incorporating F0, duration, and two discrete samples of the formant pattern.

PMID- 11248980
TI  - Influence of fundamental frequency on stop-consonant voicing perception: a case
      of learned covariation or auditory enhancement?
AB  - For stimuli modeling stop consonants varying in the acoustic correlates of voice
      onset time (VOT), human listeners are more likely to perceive stimuli with lower
      f0's as voiced consonants--a pattern of perception that follows regularities in
      English speech production. The present study examines the basis of this
      observation. One hypothesis is that lower f0's enhance perception of voiced stops
      by virtue of perceptual interactions that arise from the operating
      characteristics of the auditory system. A second hypothesis is that this
      perceptual pattern develops as a result of experience with f0-voicing
      covariation. In a test of these hypotheses, Japanese quail learned to respond to
      stimuli drawn from a series varying in VOT through training with one of three
      patterns of f0-voicing covariation. Voicing and f0 varied in the natural pattern
      (shorter VOT, lower f0), in an inverse pattern (shorter VOT, higher f0), or in a
      random pattern (no f0-voicing covariation). Birds trained with stimuli that had
      no f0-voicing covariation exhibited no effect of f0 on response to novel stimuli
      varying in VOT. For the other groups, birds' responses followed the experienced
      pattern of covariation. These results suggest f0 does not exert an obligatory
      influence on categorization of consonants as [VOICE] and emphasize the
      learnability of covariation among acoustic characteristics of speech.

PMID- 11248982
TI  - Radiation impedance of a finite circular piston on a viscoelastic half-space with
      application to medical diagnosis.
AB  - In a recent study a new analytical solution was developed and validated
      experimentally for the problem of surface wave generation on a linear
      viscoelastic half-space by a rigid circular disk located on the surface and
      oscillating normal to it. The results of that study suggested that, for the low
      audible frequency range, some previously reported values of shear viscosity for
      soft biological tissues may be inaccurate. Those values were determined by
      matching radiation impedance measurements with theoretical calculations reported
      previously. In the current study, the sensitivity to shear viscoelastic material
      constants of theoretical solutions for radiation impedance and surface wave
      motion are compared. Theoretical solutions are also compared to experimental
      measurements and numerical results from finite-element analysis. It is found
      that, while prior theoretical solutions for radiation impedance are accurate, use
      of such measurements to estimate shear viscoelastic constants is not as precise
      as the use of surface wave measurements.

PMID- 11248981
TI  - Discrimination of non-native consonant contrasts varying in perceptual
      assimilation to the listener's native phonological system.
AB  - Classic non-native speech perception findings suggested that adults have
      difficulty discriminating segmental distinctions that are not employed
      contrastively in their own language. However, recent reports indicate a gradient
      of performance across non-native contrasts, ranging from near-chance to near
      ceiling. Current theoretical models argue that such variations reflect systematic
      effects of experience with phonetic properties of native speech. The present
      research addressed predictions from Best's perceptual assimilation model (PAM),
      which incorporates both contrastive phonological and noncontrastive phonetic
      influences from the native language in its predictions about discrimination
      levels for diverse types of non-native contrasts. We evaluated the PAM hypotheses
      that discrimination of a non-native contrast should be near-ceiling if perceived
      as phonologically equivalent to a native contrast, lower though still quite good
      if perceived as a phonetic distinction between good versus poor exemplars of a
      single native consonant, and much lower if both non-native segments are
      phonetically equivalent in goodness of fit to a single native consonant. Two
      experiments assessed native English speakers' perception of Zulu and Tigrinya
      contrasts expected to fit those criteria. Findings supported the PAM predictions,
      and provided evidence for some perceptual differentiation of phonological,
      phonetic, and nonlinguistic information in perception of non-native speech.
      Theoretical implications for non-native speech perception are discussed, and
      suggestions are made for further research.

PMID- 11248983
TI  - Bioacoustic spatial perception by humans: a controlled laboratory measurement of
      spatial resolution without distal cues.
AB  - The angular spatial resolution of a wide-angle air sonar using a continuous
      transmission frequency-modulated radiation, with the output coupled binaurally to
      the auditory system of a user, was measured under restrained controlled
      conditions. This was done to determine the effect of adding a narrow central
      field of view of 9 deg to a wide-angle sonar. The target objects were three
      equidistant vertical rods initially spaced apart by 10 deg. This was varied down
      to a spacing of 4 deg. Ten nonvisual subjects achieved an angular resolution of 6
      deg. Four of these ten subjects continued learning to achieve an unexpected
      spatial resolution of 4 deg within the 9 deg central field. A mean error of
      approximately 1 deg in direction accuracy was achieved. It is inferred that the
      unique variations in the octave band ultrasonic echoes within the narrow field,
      and the invariance of the on-axis echo as one's head is turned, enables this
      angular resolution and accuracy to be achieved within the wide binaural field of
      view of 50 deg. This ability to resolve specula objects within a narrow angular
      resolution element of 9 deg is linked to the bat's ability to seemingly resolve
      object glints within a distal resolution element of less than 2 wavelengths.

PMID- 11248984
TI  - Coding of concurrent vocal signals by the auditory midbrain: effects of stimulus
      level and depth of modulation.
AB  - The segregation of concurrent vocal signals is an auditory processing task faced
      by all vocal species. To segregate concurrent signals, the auditory system must
      encode the spectral and temporal features of the fused waveforms such that at
      least one signal can be individually detected. In the plainfin midshipman fish
      (Porichthys notatus), the overlapping mate calls of neighboring males produce
      acoustic beats with amplitude and phase modulations at the difference frequencies
      (dF) between spectral components. Prior studies in midshipman have shown that
      midbrain neurons provide a combinatorial code of the temporal and spectral
      characteristics of beats via synchronization of spike bursts to dF and changes in
      spike rate and interspike intervals with changes in spectral composition. In the
      present study we examine the effects of changes in signal parameters of beats
      (overall intensity level and depth of modulation) on the spike train outputs of
      midbrain neurons. The observed changes in spike train parameters further support
      the hypothesis that midbrain neurons provide a combinatorial code of the spectral
      and temporal features of concurrent vocal signals.

PMID- 11248985
TI  - Recording depth of the heterodyne laser interferometer for cochlear vibration
      measurement.
AB  - Measurement of the cochlear partition vibration as a function of the optical-axis
      (z-axis) position in the gerbil cochlea showed that the velocity distributes over
      a range of more than 300 microm, which is larger than the thickness of the
      cochlear partition. This finding suggests that the recording depth (RD) of the
      heterodyne interferometer probably is not as small as reported in the literature.
      In the current experiment, the RD of the heterodyne laser interferometer was
      studied by measuring the velocity of a vibrating mirror as a function of the z
      axis position. Results demonstrate that the optical sectioning characteristic,
      measured by the intensity of the reflected laser beam as a function of the z-axis
      position, is not able to correctly estimate the RD of the heterodyne
      interferometer: the RD is much larger than optical sectioning, indicating a poor
      spatial resolution along the z axis.

PMID- 11248986
TI  - A consideration of the normalization that is typically included in correlation
      based models of binaural detection.
AB  - An analysis of binaural detection and new data that elucidate the nature and
      precision of normalization that must be assumed if binaural detection is
      accomplished via mechanisms that effectively compute the coefficient of cross
      correlation is presented. Based on that analysis, it is argued that the precision
      of normalization required to remove deleterious effects resulting from variations
      in the levels of the stimuli is so great that it is highly unlikely that
      normalization, per se, actually occurs as part of binarual processing. Instead,
      it appears more likely that binaural processing is accomplished via "subtractive"
      mechanisms, such as the one originally described by Durlach [J. Acoust. Soc. Am.
      35, 1206-1218 (1963)]. Within that framework, deleterious effects that could
      result from variations in the levels of the stimuli simply do not arise.

PMID- 11248987
TI  - Sodium and calcium balance in Mozambique tilapia, Oreochromis mossambicus, raised
      at different salinities.
AB  - Mozambique tilapia, Oreochromis mossambicus, born and raised in five salinities,
      viz. (relatively soft) fresh water, 25, 50, 75% and full-strength sea-water, were
      analyzed for ionoregulatory performance (in particular sodium and calcium
      handling) and growth. This tilapia regulates its blood serum mineral composition
      rather effectively; however, in sea-water serum concentrations of sodium,
      chloride and calcium (in males only) were increased, as was the serum osmolarity.
      In sea-water, the total body sodium pool was significantly enlarged. With
      increasing salinity, sodium turnover increased. Serum calcium levels and the
      total body calcium pool were more strictly controlled than those of sodium. The
      lowest density of chloride cells in opercular epithelium and the lowest branchial
      Na+-K+-ATPase activity were observed in 50% sea-water; these values were higher
      in fish kept in waters of lower or higher salinities. Fish grew more rapidly in
      brackish water. Fish kept in brackish water appeared to depend on food-related
      calcium for growth as branchial calcium uptake provides no more than 20% of
      growth related Ca-accumulation.

PMID- 11248988
TI  - Incorporation of microalgae sterols by scallop Pecten maximus (L.) larvae.
AB  - Changes in sterol composition of Pecten maximus larvae during the larval
      development stage with standard algal mixtures and unialgal diets were analysed.
      The sterol composition of four microalgae currently used in mollusc hatchery were
      also examined. Under standard algal conditions, the larvae quickly use the steryl
      ester from larvae reserves during the endotrophic and the mixotrophe phases. The
      preferential incorporation of Pavlova lutheri and T-Isochrysis sterols, rather
      than Skeletonema costatum sterols, during the larval development stage would
      indicate that S. costatum cells were poorly ingested and digested by larvae.
      Among the ingested sterols, cholesterol and stigmasterol were preferentially
      incorporated by the larvae. Conversely, the larvae appeared able to limit the
      incorporation of methylpavlovol, ethylpavlovol, and 4alpha-methylporiferasterol.
      In the unialgal experiment, the best growths were obtained with the diet richest
      in cholesterol (Chaetoceros calcitrans) and the best compromise of good growth
      and settlement rate was observed with the diet richest in C24 ethyl sterol. The
      selective incorporation of the cholesterol was confirmed by the larval rearing
      with C. calcitrans. The strong sterol dietary imprint in larvae corroborated the
      absence of an important capacity in P. maximus larvae to convert or biosynthesise
      sterol.

PMID- 11248989
TI  - Protein synthesis in the liver of Bufo marinus: cost and contribution to oxygen
      consumption.
AB  - While many estimates of the contribution of protein synthesis to metabolic rate
      exist for a variety of animals, most rely on theoretical costs of protein
      synthesis. The limitations of this approach are that theoretical costs depend
      upon variable estimates of ATP cost per peptide bond. In addition, they do not
      take into account the fact that there are protein-specific pre- and post
      translational costs. By inhibiting, protein synthesis with cycloheximide and
      measuring the resultant decrease in oxygen consumption, we have measured the
      actual cost of protein synthesis and its contribution to metabolic rate in an in
      vitro system of tissue slices from Bufo marinus. Such measurements exist for
      endotherms, but there are few such measurements for ectotherms, and none have
      been done previously for amphibians. The cost of protein synthesis in liver
      slices from B. marinus was 7.32+/-1.19 mmol O2 x g(protein)(-1) (x +/- SE, n =
      48) and protein synthesis accounted for 12% of the total metabolic rate of this
      tissue. This cost is comparable to values measured for other ectotherms although
      the contribution of protein synthesis to metabolic rate is at the lower end of
      the range of estimates for other ectotherms.

PMID- 11248990
TI  - The role of protein synthesis during metabolic depression in the Australian
      desert frog Neobatrachus centralis.
AB  - Little is known about the role of energy consuming processes during metabolic
      depression. We have shown that aestivation in the Australian desert frog
      Neobatrachus centralis is accompanied by an in vivo metabolic depression of 77%.
      Using an in vitro liver slice preparation, we have measured an in vitro metabolic
      depression in liver of 55%, with a concomitant 67% decrease in the rate of
      protein synthesis. The decrease in protein synthesis accounts for 52% of the
      metabolic depression of the tissue, but only 4.9% of the metabolic depression of
      the whole animal. No in vitro metabolic depression or decrease in protein
      synthesis during aestivation was measured in muscle, but a decrease in the low
      rate of protein synthesis in muscle in vivo could not, in any case, account for
      more than 3% of the metabolic depression of the whole animal. The liver, although
      not a quantitatively important tissue in terms of metabolic depression in vivo,
      offers the opportunity to characterise the regulation of protein synthesis in a
      system in which metabolic depression is not confounded by changes in ambient
      temperature and PO2.

PMID- 11248992
TI  - Total cholesterol, total triglycerides, and cholesterol distribution among
      lipoproteins as predictors of atherosclerosis in selected lines of Japanese
      quail.
AB  - The proportions of plasma high and low density lipoprotein cholesterol have been
      linked to inherited tendency for atherosclerosis in humans. Studies were
      conducted with Japanese quail males from lines genetically selected for high and
      low TC and a randombred (unselected) control line that were fed 0.0 or 0.5%
      cholesterol for 12 weeks. Atherosclerotic plaques were more severe in the high
      than in the low line quail and in those fed cholesterol compared to non
      cholesterol-fed quail. Serum TG, TC, VLDLC, LDLC, and HDLC were also higher in
      the high than in the low line quail and in cholesterol-fed vs. non-cholesterol
      fed quail. Significant interactions indicated that TC and LDLC concentrations
      were more affected by dietary cholesterol in the high line than in the low line.
      The low line quail maintained higher HDLC and lower LDLC than the high line.
      Regression and correlation analyses revealed that although VLDLC, LDLC, and TC
      were significant predictors of atherosclerosis in the high line birds, the
      TC/HDLC ratio was a better predictor in the low line. The Japanese quail lines
      used herein represent useful experimental models for studies of genetic
      differences in atherosclerosis in humans.

PMID- 11248993
TI  - Potential protective effects of melatonin on bone marrow of rats exposed to
      cytotoxic drugs.
AB  - Myelosuppression is the most serious, dose limiting, toxicity of cytotoxic drugs.
      Efforts to protect the bone marrow have been only variably successful, and no
      agreement exists on how to approach this problem. Melatonin, the major hormonal
      product of the pineal gland, is supposed to have both chemoprotective and
      myelostimulatory effects. This experimental study was carried out to test these
      two effects on the bone marrow of rats, daily intraperitoneally injected with 100
      microg melatonin. Injection of 10 mg aracytin for 10 days produced a significant
      (P < 0.01) decrease in red blood cells count (RBCs), total leucocytic count, as
      well as platelets count. When melatonin was injected along with aracytin, it
      would significantly increase (P < 0.05) RBC count and (P < 0.01) blood platelet
      count. Injection of melatonin after aracytin treatment would significantly
      increase (P < 0.01) RBC, total leucocytic and platelet counts in comparison with
      rats treated with aracytin only. The effects of melatonin were more clear in rats
      treated with it after aracytin injection than those treated with melatonin and
      aracytin at the same time. Furthermore, it was found that aracytin produced a
      significant (P < 0.01) decrease in serum total proteins, albumin, and
      significantly increased the (P < 0.01) albumin/globulin ratio. Melatonin
      injection would significantly increase (P < 0.01) total protein, globulin, and
      significantly decrease (P < 0.01) the albumin/glubulin ratio when injected either
      with aracytin or after aracytin treatment. These results indicate that melatonin
      protects bone marrow, lymphoid tissues from damaging effect of cytotoxic drugs,
      as well as stimulating the suppressed bone marrow.

PMID- 11248994
TI  - Lipolytic and antilipolytic responses of the Siberian hamster (Phodopus sungorus
      sungorus) white adipocytes after weight loss induced by short photoperiod
      exposure.
AB  - Short day photoperiod promotes thermogenesis and extensive weight loss in
      Siberian hamsters (Phodopus sungorus sungorus). To determine whether a change in
      hormone-sensitive lipolysis occurs after short-photoperiod exposure, some
      lipolytic responses were measured on white adipocytes isolated from animals
      exposed in warm conditions to short or Long daylight photoperiod. The body mass
      of male Siberian hamsters exposed during 11 weeks to short days (SD; light: dark,
      6:18 hr) reached only 50% of those kept in long days (LD; 16: 8 hr). In SD
      hamsters, adipose depot mass also represented approximately 50% of the LD group.
      A lower DNA content was observed in intra-abdominal fat pads of SD-hamsters.
      Lipolytic responses to noradrenaline, adrenaline, isoproterenol and ACTH were
      unchanged. However, sensitivity to the beta-3 adrenergic agonist, BRL 37344, was
      moderately increased. The major component of the adrenergic control of lipolysis
      was mediated by beta-3 adrenoceptors in both LD- and SD-Siberian hamsters. The
      limited antilipolytic effect of alpha-2 adrenergic agonists, PYY or insulin was
      rather surprising in Siberian hamsters since these inhibitory systems are
      efficient in hibernants and other photoperiod-sensitive rodents. Our results show
      that, after short photoperiod exposure, white adipose tissue mass and DNA content
      are reduced, especially in the epididymal fat pad, with only minor changes in the
      adipocyte sensitivity to lipolytic hormones.

PMID- 11248995
TI  - Short-term physiological changes in turbot and seabream juveniles exposed to
      exogenous ammonia.
AB  - Seabream and turbot juveniles (40-520 g) were exposed to constant exogenous NH5-N
      concentrations (1.27-4.27 mmol/l; pH, 8.15). In 96 hr acclimated fish, plasma TA
      N (total ammonia nitrogen) contents were positively correlated to ambient ammonia
      concentrations. The LD50 were 2.2-2.5 mmol/l TA-N in both species. There were no
      marked osmoregulatory disturbances and plasma urea-N, thyroid hormones levels and
      gill (Na-K)-ATPase activities were only affected at the highest concentrations.
      Liver GOT, GPT and GIDH activity dose-response were low and species dependent. In
      cannulated and non-cannulated turbot exposed to half 96 hr LC50 (lethal ambient
      concentration for 50% of the population), there was a rapid, pronounced and
      prolonged increase in plasma TA-N, followed by an immediate decline when
      exogenous ammonia supply was stopped. Maximum loading and unloading were observed
      within 1-3 hr. Plasma cortisol levels indicated a stressful situation in exposed
      fish (150 ng/ml) and a quick recovery capacity. In dose and time response
      experiments, the most relevant physiological indicator of ammonia stress was
      blood TA-N content. Other parameters tested led either to transient or low
      amplitude responses except when fish approached death.

PMID- 11248997
TI  - The effects of dietary astaxanthin on the carotenoid pattern of the prawn Penaeus
      japonicus during postlarval development.
AB  - Penaeus japonicus postlarvae, reared under laboratory conditions, were fed an
      astaxanthin enriched diet to the investigate carotenoid metabolic capabilities
      during the postlarval development. Animals fed astaxanthin were found to absorb
      this carotenoid. The decrease of pigment concentration in the carotenoid starved
      group is related to the duration of the experimental feeding conditions; the
      carotenoid depletion depends upon the postlarval status at the starting point. As
      has been shown for adult prawns, the carotenoid pattern of postlarval stages,
      regardless of the diet, consists mainly of free and esterified astaxanthin; the
      relative amounts of these fractions undergo slight variations depending on the
      diet.

PMID- 11248999
TI  - Different red blood cell characteristics in a primitive agnathan (M. glutinosa)
      and a more recent teleost (O. mykiss) influence their strategies for blood CO2
      transport.
AB  - This study examines how the different red blood cell (rbc) characteristics in two
      lower vertebrates, the phylogenetically primitive hagfish and a more recent
      teleost, the rainbow trout, influence their strategies for blood CO2 transport.
      Deoxygenation of the blood resulted in a significant increase in rbc CO2 content
      in hagfish, but there were no significant changes in the CO2 content of plasma or
      whole blood under these conditions. In contrast, deoxygenation increased the CO2
      content of the rbc, plasma and whole blood in the trout. These results
      demonstrate that the Haldane effect is much less important for CO2 transport in
      the hagfish as compared to the trout. The relative importance of the rbc and
      plasma in blood CO2 transport were roughly similar in hagfish and trout and were
      very different from that previously documented in another primitive vertebrate,
      the lamprey. In trout, however, the role of the rbc in CO2 carriage was increased
      upon the addition of the beta-adrenergic agonist isoproterenol (10(-5) M) to the
      blood. Taken together, these results and those recently collected for lampreys
      demonstrate that changes in rbc characteristics during vertebrate evolution have
      probably resulted in several important transitions in the strategy for blood CO2
      transport.

PMID- 11249000
TI  - Dietary cystine and liver triacylglycerols in rats: effects of dietary lysine and
      threonine.
AB  - Addition of excess cystine to a wheat gluten diet did not alter rat liver
      triacylglycerols or serum cholesterol. However, if the cystine-enriched diet was
      supplemented with lysine and threonine, rats accumulate triacylglycerols and show
      increased serum cholesterol. Increases in hepatic triacylglycerols can be
      prevented by the further addition of methionine. This diet further increases
      serum cholesterol. We conclude that accumulation of triacylglycerols in the liver
      might be due to an increased methionine requirement, induced by the addition of
      excess cystine, and therefore to choline deficiency.

PMID- 11249001
TI  - The effect of calcium-regulating hormones on transport of calcium across the
      chorioallantoic membrane of the chicken embryo.
AB  - The hormonal form of vitamin D3 (1,25(OH)2D3), parathyroid hormone (PTH), or
      appropriate vehicle were injected into the yolk sac of eggs of domestic fowl on
      days 16 and 17 of incubation. The chorioallantoic membrane (CAM) and overlying
      inner shell membrane were removed from eggs on day 18 and mounted in a Ussing
      type apparatus. Transport of calcium was assessed by monitoring movements of
      radiolabeled calcium. Transport of calcium from the chorionic aspect of the CAM
      to the allantoic aspect increased considerably with time for all treatment groups
      except the one receiving PTH. "Back-flux" of calcium (movement of calcium from
      the allantoic aspect to the chorionic) was negligible for all treatment groups at
      all sampling periods. PTH treatment did not affect flux of calcium from allantois
      to chorion but reduced flux from chorion to allantois considerably. The
      underlying cause of this effect has not been identified. The hormonal form of
      vitamin D3 did not affect flux of calcium in either direction. These data raise
      the possibility that control of calcium transport by the CAM may not be the
      primary function of the vitamin D hormone.

PMID- 11249003
TI  - Intracellular K+ activities in Aplysia gut: effects of transport inhibitors on
      the Na+ pump.
AB  - Na+ absorption by the Aplysia californica foregut is affected through an active
      Na+ transport mechanism located in the basolateral membrane of the epithelial
      absorptive cells. Since Cl- absorption by the Aplysia gut has been shown to be
      very different from that demonstrated in vertebrate gut, the present study was
      undertaken to discern if Na+ transport was also different from that observed in
      vertebrate preparations. Utilizing microelectrode technique, it was demonstrated
      that intracellular K+ activity is above electrochemical equilibrium in the
      Aplysia absorptive cells and that serosal ouabain, Ba2+ or Cd2+ abolished this
      asymmetry in K+ electrochemical potential. Neither bumetanide nor furosemide had
      any effect on intracellular K+ activities, mucosal membrane potentials or
      transepithelial potentials in the Aplysia gut preparation. These results are
      consistent with the operation of a basolateral Na+/K+ pump.

PMID- 11249002
TI  - A novel Na+/HCO3--codependent choline transporter in the syncytial epithelium of
      the cestode Hymenolepis diminuta.
AB  - Absorption of exogenous choline by the cestode Hymenolepis diminuta was found to
      be both Na+- and HCO3--dependent and, at pH 6 to 7, accounted for up to 65% of
      the total choline uptake. Na+/HCO3- dependent choline uptake was activated at
      approximately 6 mM HCO3- (EC50 approximately 9 mM), and, above 100 mM Na+, the
      rate of uptake was directly proportional to the Na+ concentration. Atempts to
      uncouple Na+-dependent uptake from HCO3--dependent uptake were not successful: K+
      depolarization was without effect on HCO3--dependent choline uptake, and use of
      valinoomycin to hyperpolarize the brush-border membrane resulted in inhibition of
      uptake. Na-/HCO3--dependent choline uptake was not associated with solvent drag.
      The Na+/HCO3--dependent choline uptake displayed a Q10 of 6.4 (27 degrees to 37
      degrees) and a relatively high activation energy of 126 kJ x mol(-1). At pH 6.0
      and 7.0, Na-/HCO3--dependent choline uptake rates were similar, but Na+/HCO3-
      dependent choline uptake was reduced at pH 5.0. The Na+/HCO3--dependent choline
      uptake, at pH 7.0, displayed a Kt of approximately 500 microM and a Vmax of 4.01
      pmol x mg wet weight(-1) x min(-1). The Na+/HCO3--dependent choline uptake was
      hemicholinium-3 sensitive, but not significantly inhibited by 200 microM
      bumetanide, 100 microM amiloride, benzamil, or EIPA or by 1 mM 4,4'
      diisothiocyano-2,2'-stilbene disulfonate (DIDS) or 4-acetamido-4'
      isothiocvanostilbene-2,2'-disulfonic acid (SITS). Although it remains to be shown
      that HCO3- uptake is coupled directly to both choline and Na+ uptake, the data
      suggest that choline up take occurs via choline/Na+/HCO3--co-trans porter.

PMID- 11249004
TI  - Species differences in substrate specificity of lipoprotein lipase purified from
      chickens and rats.
AB  - Kinetic parameters of chicken and rat lipoprotein lipase (LPL) were determined in
      the incubation in vitro with various monoacid triacylglycerol emulsion and plasma
      lipoproteins. In rat- and chicken-LPL there is an inverse relationship between
      the hydrolytic rate by both LPL and the increased acyl-chain unsaturation of
      monoacid triacylglycerol; C18:1>C18:2>C18:3. The rat LPL catalyzed hydrolysis of
      saturated monoacid triaclyglycerol increased with an increase of chain length as
      C16>C14>C12, whereas in chicken LPL hydrolytic rate of C12 was higher than C14
      and C16 triaclyglycerol. Vmax of rat- and chicken-LPL for chylomicron and VLDL
      were higher but apparent Km for those were lower than other lipoproteins. In
      chicken, Vmax and apparent Km of LPL for VLDL were almost the same as those for
      chylomicron, whereas in rat, Vmax of LPL for VLDL was twice that of chylomicron
      with the same apparent Km. The chicken and rat VLDL with different particle size
      prepared by Bio-Gel A50 gel chromatography were similarly hydrolyzed by LPL,
      while the hydrolysis of small chicken-chylomicron particles was inclined to be
      higher than that of the large particles. These results show species differences
      between chickens and rats in the substrate specificity of LPL.

PMID- 11249005
TI  - Genetic variation and functional properties of Atlantic cod hemoglobins:
      introducing a modified tonometric method for studying fragile hemoglobins.
AB  - Hemoglobin polymorphism in Atlantic cod has been investigated with respect to
      physiological performance at 10, 15 and 20 degrees C applying a modified
      tonometric method for O2 equilibrium analysis with full control of the
      equilibrating gas mixture. The results did not indicate any dissociation of the
      hemoglobins by a reduction in cooperativity and a parallel increase in affinity
      during the analytical procedure in contrast to the original tonometric method.
      With the applied preparation technique, we could store the hemolysate for 70 days
      at -25 degrees C without any significant changes in the O2 binding properties (P
      < 0.05) demonstrating the high quality of this procedure for analysing fragile
      fish hemoglobins. The present investigation demonstrates that the oxygen affinity
      of the hemoglobins varied between the genotypes. At all temperatures, except 20
      degrees C and pH 8.0, Hb-I(2/2) had a higher O2 affinity than Hb-I(1/1). These
      results conform with previous results (16), suggesting Hb-I(2/2), the genotype
      which is the dominant allele in northern areas, to be the most efficient O2
      carrier at low temperatures. The highest O2 affinity, however, was found for Hb
      I(2/2b), supporting the results of Fyhn et al. (9), that this genotype is more
      restricted to coastal and warmer water and thus a better marker of the coastal
      population. Our results further suggest a correlation between genotype specific
      growth rates and oxygen affinities at all temperatures studied, with the highest
      growth rates observed in those genotypes having the highest O2 affinities. In
      conclusion, the hemoglobin polymorphism of cod seems to be correlated with
      physiological performance.

PMID- 11249006
TI  - Swimming performance, venous oxygen tension and cardiac performance of coronary
      ligated rainbow trout, Oncorhynchus mykiss, exposed to progressive hypoxia.
AB  - We performed in vivo studies to examine the idea that cardiac work is impaired in
      rainbow trout (Oncorhynchus mykiss) below a certain venous PO2 threshold. We
      hypothesized that coronary-ligated fish, swimming continuously at a reasonably
      high water velocity (1.5 body lengths x s(-1)) and exposed to progressive
      hypoxia, would fatigue at higher venous PO2 and ambient water PO2 compared with
      sham-operated fish. However, we found that both the lowest venous PO2 that
      supported hypoxic swimming (9.9 torr for coronary-ligated fish and 11.1 torr for
      sham-operated fish) and the venous PO2 at fatigue (7.8 torr and 8.6 torr,
      respectively) were the same for coronary-ligated and sham-operated fish. Also,
      both groups quit swimming at the same water PO2 heart rate and hematocrit.
      Nevertheless, significant differences in cardiac performance did exist between
      the two groups. Whereas ventral aortic blood pressure (Pva) increased
      significantly with hypoxic swimming in sham-operated fish, there was no such
      increase in coronary-ligated fish. In addition, cardiac arrhythmias occurred in
      coronary-ligated fish at fatigue, and these fish were slower to recover from
      exhaustion. We believe that the venous PO2 threshold to support cardiac
      performance in the absence of a coronary supply was between 7.8 and 9.9 torr.
      Furthermore, we suspect that the low PO2 in coronary-ligated fish effectively
      lowered their myocardial O2 demand. Uncertainty still exists regarding whether or
      not the venous PO2 threshold lies between 8.6 and 11.1 torr in sham-operated
      fish.

PMID- 11249007
TI  - Vitamin A deficiency reduces the responsiveness of pineal gland to light in
      Japanese quail (Coturnix japonica).
AB  - Synthesis of melatonin in pineal gland is under the control of light environment.
      The recent finding of the presence of rhodopsin-like photopigment (pinopsin) and
      retinal in the avian pinealocytes has led to a hypothesis that vitamin A is
      involved in photoresponses of the pineal gland. We have thus analyzed the effect
      of vitamin A deficiency on the regulatory system of melatonin synthesis in the
      pineal gland of Japanese quail. Depletion of vitamin A from Japanese quails was
      attained by feeding them with a vitamin A-free diet supplemented with retinoic
      acid. In the vitamin A-deficient birds, diurnal rhythm in melatonin production
      persisted such that the phase of the wave was similar to that seen in the control
      birds. However, the amplitude of the nighttime surge of pineal melatonin was
      damped by vitamin A deficiency. When the control birds were briefly exposed to
      light at night, pineal melatonin dropped to the daytime level. In contrast, only
      slight decrease was observed in the vitamin A-deficient quails. The light
      responsiveness was restored after feeding the vitamin A-deficient quails with the
      control diet for 1 week. These results indicate that vitamin A plays essential
      roles in maintaining sufficient responsiveness of the avian pineal gland to
      photic input.

PMID- 11249009
TI  - Oxygen consumption, carbon dioxide excretion and respiratory quotient of larval
      lampreys (Mordacia mordax) in air.
AB  - The standard rates of O2 consumption of larval Mordacia mordax (weight range 1.3
      2.3 g), after these ammocetes had been in humidified air for 18 hr, were 26.8,
      46.3 and 71.2 microL x g(-1) x hr(-1) at 10, 15 and 20 degrees C, respectively.
      The corresponding rates of CO2 excretion were 20.7, 35.6 and 54.1 microL x g(-1)
      x hr(-1). The RQs at the three temperatures were essentially identical (0.76 or
      0.77) and similar to that of adults of the lamprey Geotria australis in air at 15
      degrees C. The above RQs for ammocoetes, which are probably similar to those that
      would be recorded in water, are consistent with the view that the aerobic
      respiration of these animals relies predominantly on lipid as an energy source,
      but that some energy is derived from carbohydrate and/or protein. The RQs for
      larval and adult lampreys in air lie well within the range recorded for
      amphibious fishes in air.

PMID- 11249010
TI  - Influence of body mass, age, and maturation on specific oxygen consumption in a
      freshwater cichlid fish, Cichlasoma nigrofasciatum (Gunther, 1869).
AB  - The oxygen consumption of a freshwater convict cichlid (Cichlasoma
      nigrofasciatum) was determined throughout the fish development from age 74 days
      to 403 days, covering the period before and after maturation. The specific oxygen
      consumption decreases with increasing age. The decrease in metabolic rate appears
      rather in distinct phases. A small increase in the average specific metabolic
      rate (mainly from the bigger fish) around age 200 days suggests an involvement of
      internal changes in the fish during a transition period from "young" state to
      "mature" state. The relationship between the specific oxygen consumption and body
      mass is determined by maturation and age. Before reaching maturation (before age
      200 days) the correlation between specific oxygen consumption and body mass is
      negative for "young" fish of the same age. After age 200 days, no correlation
      between both parameters could be found. We suggest from this study that both
      factors "age" and "size" of the organism have to be considered for determining
      the metabolism, especially in fish. This study indicates that even in fish, which
      retain a continuous growing capability until they die, the decrease in the
      specific oxygen consumption is related to the aging process.

PMID- 11249011
TI  - The composition of Naja naja venom samples from three districts of West Bengal,
      India.
AB  - The variation in the composition of Naja naja venoms from three neighbouring
      districts of West Bengal, eastern India and the corresponding differences in the
      severity of pathogenesis due to venom composition variation are reported. These
      venom samples differ with respect to chromatographic elution profile and enzyme
      activity associated with each fraction. Presence of higher quantities of basic
      phospholipase and plasma protein hydrolase in the venom samples of Burdwan and
      Purulia make them more toxic than Midnapur venom sample. A polyvalent antivenom
      manufactured in western India was hardly effective in neutralizing the
      pathobiological manifestation of the venom samples from eastern India.

PMID- 11249013
TI  - Heat-induced germ cell deficiency in the teleosts Odontesthes bonariensis and
      Patagonina hatcheri.
AB  - Pathological or experimental elevation of testicular temperature is known to
      trigger degeneration and disappearance of germ cells in scrotal mammals. In
      contrast, there are no reports of heat-induced germ cell deficiency in males of
      non-scrotal mammals and other vertebrate taxa, nor in females of any species.
      This study describes the induction of germ cell deficiency up to complete
      sterility in the teleosts Patagonina hatcheri and Odontesthes bonariensis by
      rearing larvae and juveniles for prolonged periods at incipient lethal, high
      temperatures (27-28.5 and 29 degrees C, respectively). It was shown that female
      germ cells are also heat-sensitive and disappear under high temperatures. The
      potential implications of these findings for physiological, ecological, and
      environmental studies and the usefulness of heat-induced germ cell-deficient fish
      in research and animal production are discussed.

PMID- 11249012
TI  - Effects of chronic treatment with noradrenaline or a specific beta3-adrenergic
      agonist, CL 316 243, on energy expenditure and epididymal adipocyte lipolytic
      activity in rat.
AB  - 1. The effects of 7 days exposure to a specific beta3-adrenergic agonist, CL 316
      243 (1 mg/kg x 24 hr), or to the physiological hormone, noradrenaline (5 mg/kg x
      24 hr), were tested on energy expenditure and on in vitro lipolysis in male
      Sprague-Dawley rats. 2. At the second day of treatment, the total energy
      expenditure and the resting metabolic rate were increased by 20 and 30%,
      respectively, in the CL-treated group. Under the same conditions, a dose five
      times higher of NA increased the resting metabolic rate by 11% without any
      significant change in the total daily energy expenditure. 3. The CL-treated group
      showed a lower weight gain, correlated with a significant reduction in
      retroperitoneal adipose tissue weight. Both treatments resulted in a marked
      desensitization (increased EC50 values) of the NA stimulated lipolysis of
      epididymal adipocytes. The effects of both treatments on maximal lipolysis were
      opposite. Indeed, chronic NA-treatment decreased the responsiveness of lipolysis
      while chronic treatment with CL increased the maximal stimulation of lipolysis to
      NA. Furthermore, dose-response curve for CL on lipolysis showed a marked
      functional desensitization of beta3-adrenergic response. 4. Our results
      demonstrate the high selectivity of beta3-adrenergic agonists to stimulate whole
      body energy expenditure and lipid mobilization in rodents. The present results
      point out for the first time an adrenergic desensitization of the lipolytic
      response after chronic administration of a beta3-agonist.

PMID- 11249014
TI  - Neuronal activity related to spontaneous and capsaicin-induced rhythmical jaw
      movements in the rat.
AB  - Intraoral capsaicin induced rhythmical jaw movements (RJM) in anesthetized rats.
      Neurons in the trigeminal spinal nucleus caudalis or the cortico-peduncular (CP)
      axons were extracellularly recorded. Capsaicin excited dose-dependently most
      caudalis neurons, which were activated by stimulation of the oral cavity and/or
      the tooth pulp and activated during spontaneous or induced RJM. Ten of 55 CP
      axons were antidromically activated by stimulation of the contralateral
      trigeminal motor nucleus. All antidromic and 29 other CP axons discharged prior
      to the spontaneous RJM, but most of them did not during capsaicin-induced RJM.
      These neuronal activities possibly initiate spontaneous RJM although the
      activities of caudalis neurons are necessary for capsicin-induced RJM.

PMID- 11249015
TI  - Valine transport and biodiversity of Leuconostoc wild strains from French raw
      milk cheeses.
AB  - The rate of L-valine transport in whole cells of Leuconostoc was at the maximum
      at 30 degrees C, pH 6.0 in the presence of an energy source. Transport was
      inhibited by 40-55%, in the presence of the ionophores (valinomycin, nigericin or
      monensin), and uncouplers (carbonyl cyanide-m-chloro-phenylhydrazone or 2,4
      dinitrophenol) confirming the previously described delta p-driven branched-chain
      amino acid transport system described in cytoplasmic membranes (Winters et al.,
      1991, Appl. Environ. Microbiol., 57, 3350-3354). Sulfhydryl group reagents (p
      chloro-mercuribenzoate, iodoacetate and N-ethyl maleimide) all inhibited valine
      transport by 60-70%, indicating that valine is actively transported at high
      valine concentration. Three kinetically distinguishable transport systems were
      identified for each strain using whole cells, confirming results obtained with
      membranes. L-valine transport Kt and Vmax could be an additional tool to estimate
      the biodiversity of 18 Leuconostoc strains belonging to the dominant flora of
      French raw milk cheeses. Kt values varied from 20 to 510 nmol/l for the very high
      affinity system, from 26 to 427 pmol/l for the high affinity system and from 0.65
      to 4.40 mmol/l for the low affinity system. No correlation existed between valine
      transport rates and a particular strain's ability to acidify milk or complex
      media, suggesting that valine transport is not a growth-limiting function in
      species of the genus Leuconostoc.

PMID- 11249016
TI  - Comparative study of temperate bacteriophages isolated from Yersinia.
AB  - 170 Yersinia strains belonging to various species were investigated for the
      presence of temperate bacteriophages. By induction with mitomycin C seven phages
      were isolated from Y. enterocolitica strains and one phage from a Y.
      frederiksenii strain. The phages were characterized on the basis of their
      morphology, host range, genome size, DNA homology, and protein composition. They
      belong to different phage families and reveal narrow to moderate wide host
      ranges. Some of the isolated phages were able to infect pathogenic as well as
      nonpathogenic strains of Y. enterocolitica. The genomes of all isolated phages
      were found to be composed of double stranded DNA ranging from about 40 to 60 kb.
      In addition to the analysed phages, a number of putative phages were induced in
      strains of Y. frederiksenii, Y. kristensenii, Y. intermedia, and Y. mollaretii.
      The putative phages were identified by isolation of phage DNA from cell free
      lysates but could not be propagated on indicator strains. Southern hybridization
      experiments revealed relationships between phages belonging to different
      families. Moreover, DNA homologies were observed between phages isolated from
      nonpathogenic Yersinia strains and a phage which was isolated from a pathogenic
      Y. enterocolitica serogroup O:3 strain.

PMID- 11249017
TI  - Partial sequencing of the hrpB and endoglucanase genes confirms and expands the
      known diversity within the Ralstonia solanacearum species complex.
AB  - We determined partial hrpB and endoglucanase genes sequences for 30 strains of
      Ralstonia solanacearum and one strain of the blood disease bacterium (BDB), a
      close relative of Ralstonia solanacearum. Sequence comparisons showed high levels
      of variability within these two regions of the genome involved in pathogenicity.
      Phylogenetic analysis based upon sequence comparisons of these two regions
      revealed three major clusters comprising all Ralstonia solanacearum isolates, the
      BDB strain constituted a phylogenetically distinct entity. Cluster 1 and cluster
      2 corresponded to the previously defined divisions 1 and 2 of Ralstonia
      solanacearum. Moreover, two subclusters could be identified within cluster 2. The
      last cluster, designated cluster 3 in this study, included biovar 1 and N2
      strains originating from Africa. This recently described group of strains was
      confirmed to be clearly different from the other strains suggesting a separate
      evolution from those of both divisions 1 and 2.

PMID- 11249018
TI  - Hydrogenophaga intermedia sp. nov., a 4-aminobenzenesulfonate degrading organism.
AB  - The taxonomic status of a gram-negative, oxidase positive rod (strain S1) able to
      degrade 4-aminobenzenesulfonate was studied using a polyphasic approach.
      Chemotaxonomic investigations of quinones and polar lipids established the
      allocation of this strain to the beta-subclass of the Proteobacteria and revealed
      similarities to Hydrogenophaga palleronii. 16S rRNA sequence comparisons
      demonstrated that this strain clusters phylogenetically with H. palleronii and H.
      taeniospiralis, but clearly represents a new species. The fatty acid patterns and
      substrate utilization profile displayed similarity to the characteristics of the
      four validly published species of Hydrogenophaga, although clear differentiating
      characters were also observed. No close similarities between the type strains of
      H. palleronii and H. taeniospiralis were detected in hybridization experiments
      with the genomic DNAs. On basis of these results, the new species Hydrogenophaga
      intermedia sp. nov. is proposed, with the type strain S1T (= DSM 5680).

PMID- 11249019
TI  - Genomic fingerprints, ARDRA profiles and quinone systems for classification of
      Pasteurella sensu stricto.
AB  - In order to investigate the relationships between species of the genus
      Pasteurella sensu stricto such as Pasteurella multocida, Pasteurella canis,
      Pasteurella stomatis, Pasteurella dagmatis, Pasteurella avium, Pasteurella
      volantium, Pasteurella gallinarum, Pasteurella species A, Pasteurella species B
      and "Pasteurella leonis" MCCM 00659 their genomic fingerprints and ARDRA profiles
      were compared and their quinone systems were analysed. Visual comparison of band
      patterns from rep-PCR (ERIC-, REP- and BOX-PCR) and the analyses of the combined
      band patterns by UPGMA (unweighted pair group method with averages) dendrogram
      derived from the combined fingerprint profiles demonstrated that each strain
      displays a distinct genomic fingerprint. In members of the same species several
      similarities in the band patterns were observed. Combined ARDRA profiles,
      obtained after digestion of amplified 23S rRNA coding genes with the enzymes
      DdeI, MseI and RsaI, revealed a dissection of the members of the genus
      Pasteurella sensu stricto into two groups which was in agreement with the two
      groups obtained from our analyses of the quinone systems. These two groups
      corresponded with the two phylogenetically determined subclusters 3A and 3B
      described previously. The species of subcluster 3A displayed a quinone system
      with ubiquinone Q-7 (32-56%) and ubiquinone Q-8 (44-63%) as major compounds.
      Members of subcluster 3B had a quinone system with ubiquinone Q-8 (86-97%) as the
      major compound. Based on these results it can be suggested that the genus
      Pasteurella sensu stricto should be restricted to the species of subcluster 3B
      including the species Pasteurella multocida, Pasteurella canis, Pasteurella
      stomatis, Pasteurella dagmatis and Pasteurella species B. In addition, evidence
      was found which would indicate that: 1) Pasteurella canis MCCM 00927 is misnamed
      and should be reclassified with Pasteurella multocida; 2) Pasteurella multocida
      subsp. septica may be classified as a separate species; and 3) "Pasteurella
      leonis" MCCM 00659 represents a separate species within subcluster 3B and thus
      could be described as a species of Pasteurella sensu stricto (also in a redefined
      genus) when more strains become available.

PMID- 11249020
TI  - Rapid amplified ribosomal DNA restriction analysis (ARDRA) identification of
      Lactobacillus spp. isolated from fecal and vaginal samples.
AB  - Amplified ribosomal DNA restriction analysis (ARDRA) was used to identify
      different species of Lactobacillus isolated from human faeces and vagina. PCR
      ARDRA was performed using a set of four restriction enzymes, able to
      differentiate fourteen species of Lactobacillus. The PCR-ARDRA procedure
      described in this paper was shown to be a reliable and rapid method for
      identifying Lactobacillus species from intestinal and vaginal microflora at
      species and subspecies level.

PMID- 11249021
TI  - A rapid PCR based method to distinguish between Lactococcus and Enterococcus.
AB  - Phenotypic characterisation of Lactococcus and Enterococcus species remains
      unreliable as strains of both genera have been isolated which do not conform to
      the traditional criteria for separation of these genera. A bank of 131 isolates
      was phenotypically characterised by three methods: (a) traditional broth tests,
      (b) API Rapid ID 32 Strep and (c) BBL Crystal ID kits. Differences in genus
      designation between commercial kits were evident for 12 strains (9%), while 7
      strains (5%) remained unidentified by either kit. Published 16S rRNA sequences
      were aligned and used to design genus-specific primers which, when used in
      separate PCR reactions, were capable of distinguishing all type strains of
      Lactococcus and Enterococcus. These primers did not react with known species of
      Streptococcus, Pediococcus, Lactobacillus, Leuconostoc or Tetragenococcus.
      Isolates which could not be identified by phenotype were assigned to either genus
      on the basis of the gene primers.

PMID- 11249022
TI  - Identification and characterization of carnobacteria associated with the gills of
      Atlantic salmon (Salmo salar L.).
AB  - Using the surface plate technique, the population level of aerobic bacteria,
      occurring in the gills of Atlantic salmon (Salmo salar L.), was determined to be
      approximately 3 x 10(4) g(-1). Of 100 isolates investigated, 58 were gram
      negative. Out of the 42 gram-positive isolates, 26 belonged to the carnobacteria,
      of which ten were further identified on the basis of 16S rDNA sequence analysis
      and AFLP fingerprinting. All were identified as Carnobacterium piscicola-like.
      These carnobacteria strains were also screened for their ability to produce
      growth inhibitory compounds active against the fish pathogens Aeromonas
      salmonicida subsp. salmonicida, Vibrio anguillarum and Vibrio salmonicida. Nine
      out of the ten C. piscicola isolates tested strongly inhibited growth of the
      three pathogens.

PMID- 11249023
TI  - The filamentous bacterial morphotype 'Nostocoida limicola' I contains at least
      two previously described genera in the low G+C gram positive bacteria.
AB  - Isolates of eight bacterial filaments fitting the published morphological
      description of 'Nostocoida limicola' I were obtained from the mixed liquor of
      four different Australian and one Czech Republic activated sludge plants by
      micromanipulation. On the basis of their near complete (Ben 200 and Ben 201), or
      partial (Ben 77, Ben 78, Ben 202, Ben 203, Ben 204 and Ben 205) 16S rRNA gene
      sequences, six of these isolates were 99.3-100% similar to Lactosphaera pasteurii
      and Trichococcus flocculiformis, a bulking filament only reported previously in
      Germany. The other two (Ben 203 and Ben 204) were 99.9% similar to Streptococcus
      suis. Hence, all are in the low mol % G+C gram-positive bacteria division of the
      Bacteria. On this evidence 'N. limicola' I is phylogenetically unrelated to
      'Nostocoida limicola' II, which is now known to be in the Actinobacteria, even
      though these two filamentous bacteria appearing in activated sludge systems have
      been considered to be closely related to each other historically.

PMID- 11249024
TI  - Molecular sequence analyses of the intergenic spacer (IGS) associated with rDNA
      of the two varieties of the pathogenic yeast, Cryptococcus neoformans.
AB  - The pathogen Crytococcus neoformans has been traditionally grouped in two
      varieties, C. neoforrmans var. neoformans (serotypes A, D and AD) and C.
      neoformans var. gattii (serotypes B and C). A recent taxonomic evaluation of C.
      neoformans var. neoformans described C. neoformans var. grubii as a new variety
      represented by serotype A isolates. Despite immunological, biochemical,
      ecological and molecular differences the three varieties are classified within
      one species. We examined the genetic variability of one hundred and five clinical
      and environmental isolates that included all varieties and serotypes. Sequence
      analysis of the intergenic spacer (IGS) associated with rDNA revealed significant
      differences in nucleotide composition between and within the varieties. Parsimony
      analysis showed five different genotypes representing distinct genetic lineages.
      Although there was a high degree of relatedness between serotype and genotype
      this relatedness was not exclusive as serotypes were not restricted to one
      particular genotypic group. Serotyping and sequence analyses indicate that C.
      neoformans var. grubii (serotype A) should not be recognized as a separate
      variety. Based on this study we propose to accept two separate species, C.
      neoformans (serotypes A, D and AD) and C. bacillisporus (serotypes B and C
      synonymous with C. neoformans var. gattii).

PMID- 11249025
TI  - Characterization of Gibberella fujikuroi complex isolates by fumonisin B1 and B2
      analysis and by RAPD and restriction analysis of PCR-amplified internal
      transcribed spacers of ribosomal DNA.
AB  - Twenty nine isolates of Fusarium spp. (twenty four of them belonging to the
      Gibberella fujikuroi complex) isolated from banana and corn from different
      geographical regions were analyzed for their ability to produce fumonisins B1 and
      B2 and for genetic relatedness using random amplified polymorphic DNA (RAPD) and
      restriction analysis of PCR amplification products of the 5.8s ribosomal DNA
      intervening internal transcribed spacer regions (ITS I-5.8S-ITS II). For RAPD
      analysis, six of twenty oligonucleotide primers were selected after testing with
      five Fusarium spp. isolates and used to characterize 24 additional isolates. DNA
      fragments from the 29 isolates of Fusarium spp., which were approximately 560 bp,
      were amplified with the universal primers ITS1 and ITS4. The restriction enzymes
      HaeIII, MboI, HpaII and MspI were useful for distinguishing the isolates. The
      RAPD analysis permitted to find interspecific differences among the isolates of
      Fusarium spp., between isolates with low and high capacity of fumonisin
      production and among isolates from different hosts. The restriction fragment
      length polymorphism (RFLP-PCR) analysis permitted to distinguish among different
      species of Fusarium. In combination with morphological analysis, the results of
      this research may find an application for the diagnosis of unknown Fusarium spp.
      and, particularly, for the characterization of fumonisin-producing isolates,
      which may be very useful in the food technology field.

PMID- 11249026
TI  - How quantitative is quantitative PCR with respect to cell counts?
AB  - Quantitative diagnostic PCR systems based upon rDNA targeted primer and probe
      combinations were developed for the detection of Escherichia coli, Pseudomonas
      aeruginosa, Pseudomonas fluorescens, Pseudomonas alcaligenes, enterococci,
      Staphylococcus aureus, and Staphylococcus epidermidis. Primers and probes were
      designed in silico using the ARB software package (TU Munich) in combination with
      Primer Design software of PE Applied Biosystems. Purified genomic DNA or
      bacterial cells of target and reference organisms were used for the evaluation of
      the PCR assays applying the TaqMan technique on an ABI PRISM TM 7700 Sequence
      Detection System (PE Applied Biosystems). Sensitive, reliable and reproducible
      quantification of target rDNA could be achieved applying primer-probe
      combinations that mediate in vitro amplification of DNA fragments smaller than
      100 base pairs. Large amounts of non target DNA (1 mg per sample) remarkably
      affected the quantification potential of the approach resulting in an
      underestimation of the amounts of target DNA. One of the principal goals was to
      use quantitative PCR to study the correlation of gene and cell numbers depending
      on the growth behavior of target organisms and to explore the potential to
      estimate cell numbers from target DNA quantification. A clear correlation of rDNA
      quantification and bacterial growth was observed, however, cell numbers cannot
      directly be estimated from quantitative PCR data, given that the cellular genome
      content varies with the growth phase of the organisms. In the case of Escherichia
      coli the cell numbers which could be assigned to a certain number of rDNA targets
      varied reasonably depending upon the growth phase of batch cultures.

PMID- 11249027
TI  - A nested array of rRNA targeted probes for the detection and identification of
      enterococci by reverse hybridization.
AB  - Complete 23S and almost complete 16S rRNA gene sequences were determined for the
      type strains of the validly described Enterococcus species, Melissococcus pluton
      and Tetragenococcus halophilus. A comprehensive set of rRNA targeted specific
      oligonucleotide hybridization probes was designed according to the multiple probe
      concept. In silico probe design and evaluation was performed using the respective
      tools of the ARB program package in combination with the ARB databases comprising
      the currently available 16S as well as 23S rRNA primary structures. The probes
      were optimized with respect to their application for reverse hybridization in
      microplate format. The target comprising 16S and 23S rDNA was amplified and
      labeled by PCR (polymerase chain reaction) using general primers targeting a wide
      spectrum of bacteria. Alternatively, amplification of two adjacent rDNA fragments
      of enterococci was performed by using specific primers. In vitro evaluation of
      the probe set was done including all Enterococcus type strains, and a selection
      of other representatives of the gram-positive bacteria with a low genomic DNA G+C
      content. The optimized probe set was used to analyze enriched drinking water
      samples as well as original samples from waste water treatment plants.

PMID- 11249028
TI  - Optimization of reverse hybridization in microplates coated with rRNA targeted
      oligonucleotide probes.
AB  - Among the modern molecular techniques for the identification of microorganisms
      the most straightforward way is through direct hybridization with rRNA/rDNA
      targeted probes. In this study, the optimization of the experimental procedures
      for the reverse hybridization technique in 96-well microplates is described using
      both synthetic model oligonucleotides (18 b) and amplified DNA (app. 4500 bp).
      Three different types of plates were compared (Maxi Sorp, NucleoLink, CovaLink).
      Plates made from nonchemically modified polystyrene which are conventionally used
      in immunoassays (MaxiSorp) proved to be an economic alternative for plates
      offering chemically modified tailor-made surfaces. Phosphorylation of the
      oligonucleotide probe was not necessary for successful immobilization whereas
      with 5'-terminal hexa-deoxyadenosine tailed capture oligonucleotides an enhanced
      sensitivity of the assay was observed. Variation of the stringency by adjusting
      different concentrations of formamide during the washing step ensures high probe
      specificity and therefore allows reliable identification of the microorganisms.
      The assay can be performed in less than 4 hours using pre-coated plates which can
      be stored for several weeks. After dissociation of the target DNA/capture probe
      duplex with an alkaline denaturing solution rehybridization is possible.

PMID- 11249029
TI  - Molecular retrieval of large 16S rRNA gene fragments from an Italian rice paddy
      soil affiliated with the class Actinobacteria.
AB  - We designed a PCR assay specific for the 16S rRNA genes of members of the class
      Actinobacteria, and created a clone library using the amplification product of
      total community DNA extracted from anoxic Italian rice field soil. Eighteen out
      of 27 randomly sequenced clones were affiliated with Actinobacteria, i.e.
      Frankineae, Corynebacterineae, Micrococcineae, the bacterium candidatus
      "Microthrix parvicella" and a novel taxonomically undefined cluster.

PMID- 11249030
TI  - Divergent Bradyrhizobium symbionts on Tachigali versicolor from Barro Colorado
      Island, Panama.
AB  - Relationships of root-nodule bacteria from the tree Tachigali versicolor (legume
      subfamily Caesalpinioideae) were analyzed for 20 isolates sampled from juvenile
      plants growing on Barro Colorado Island (BCI), Panama. Bacterial genetic
      diversity appeared to be low. In the highly polymorphic 5' intervening sequence
      region of 23S rRNA, all isolates had the same length variant. A 472 bp segment
      spanning this region was sequenced in four isolates, and all proved to be
      identical at every nucleotide position. RFLP analysis of a 868 bp fragment of the
      nitrogenase alpha-subunit gene likewise indicated that all 20 isolates shared an
      identical set of restriction sites. Phylogenetic analysis of both partial 23S
      rRNA and nearly full-length 16S rRNA sequences showed that bacterial symbionts of
      T. versicolor fall into the genus Bradyrhizobium. However, they are divergent
      from the bradyrhizobia associated with other BCI legumes, as well as from other
      currently known bacteria in this genus. Inoculation tests with two promiscuously
      nodulating legumes showed that bacteria from T. versicolor were unable to form
      nodules on Vigna unguiculata, but did nodulate Macroptilium atropurpureum,
      although the nodules lacked nitrogen fixation activity. The association of
      Tachigali with a divergent lineage of Bradyrhizobium is noteworthy in view of
      this plant's position within a clade of the mostly non-nodulating "primitive"
      legume subfamily Caesalpinioideae that gave rise to the predominantly nodulating
      subfamily Mimosoideae.

PMID- 11249031
TI  - Bacterial community changes and enrichment of Burkholderia-like bacteria induced
      by chlorinated benzoates in a peat-forest soil-microcosm.
AB  - Bacterial community shifts in a peat-forest soil spiked with 3-chlorobenzoate
      (3CBA) or 2,5-dichlorobenzoate (2,5DCB) were monitored by PCR-amplification of
      the V6 to V8 regions of the 16S rRNA and rDNA, followed by separation of the
      amplicons by temperature gradient gel electrophoresis. 3CBA disappeared to non
      detectable levels after 15 days by a biologically mediated process, while 2,5DCB
      remained at the initial concentration values. The experiments were conducted
      under microcosms systems. Addition of the chlorinated benzoates to the soil
      resulted in a rapid decrease of the microbial diversity, as judged by a time
      dependent reduction in the number of amplicons detected by temperature gradient
      gel electrophoresis. Few amplicons specifically enriched in the spiked soils were
      cloned and characterised by sequence analysis. The identity of the cloned DNA and
      the corresponding soil amplicons was confirmed by hybridisation with a
      radioactively labelled V6-probe. Analysis of the 16S rDNA sequences indicated
      that Burkholderia-related bacteria dominated the enriched soil populations under
      3CBA stress. In addition, enrichment cultures growing on 3CBA as sole C-source
      were obtained from the respective spiked soil, which were found to contain
      bacteria with identical 16S rDNA sequences as those induced by 3CBA stress in
      soil.

PMID- 11249032
TI  - Characterization of oxytetracycline-resistant heterotrophic bacteria originating
      from hospital and freshwater fishfarm environments in England and Ireland.
AB  - This ecotaxonomic study compared the antibiotic tolerance among culturable
      oxytetracyline-resistant (Ot(r)) heterotrophic strains isolated from two aquatic
      environments representing human activities in health care and aquaculture, namely
      hospital effluents and freshwater fishfarms. Using a standardized methodology,
      samples taken in England and Ireland were analyzed to determine the antibiotic
      tolerance profiles of two groups of culturable Ot(r) bacterial isolates at the
      intergeneric and intrageneric level comprising heterotrophs (189 strains) and
      mesophilic Aeromonas spp. (153 strains), respectively. Antibiogram data of
      heterotrophic isolates revealed that Irish hospital strains comprised higher
      frequencies of multi-tolerance than those originating from fishfarm environments
      whereas a reverse correlation was found among the English heterotrophs.
      Polyphasic identification of the isolates using fatty acid analysis and API 20E
      profiling showed that this difference arose from the unique taxonomic diversity
      within each heterotrophic strain set. Acinetobacter (27%) and Brevundimonas (22%)
      were predominant among the Irish Ot(r) fishfarm isolates, whereas isolates
      originating from the English aquaculture site almost entirely consisted of
      Stenotrophomonas maltophilia (86%) exhibiting high frequencies of tolerance to
      ampicillin and streptomycin. Within both the English and the Irish Ot(r)
      Aeromonas strain sets, on the other hand, the hospital strain sets displayed
      higher numbers of multi-tolerant isolates than to fishfarm isolates although
      country-specific differences were observed for individual antimicrobial agents.
      The typical occurrence of kanamycin-tolerant aeromonads in the Irish hospital
      site could to some extent be linked to the typical presence of A. hydrophila DNA
      hybridization group (HG) 3 strains as determined by fatty acid analysis and
      fluorescent amplified fragment length polymorphism (FAFLP) fingerprinting.
      Essentially, these data indicate that tolerance profiles in a specific
      environment of one country do not necessarily reflect the corresponding tolerance
      profiles of the same type of environment in another country, and this mainly as a
      result of the unique taxonomic composition of each site. Ot(r) representatives of
      Acinetobacter, S. maltophilia, and A. veronii biovar sobria HG8 were common to
      most if not all of the four sites under study, indicating that these three taxa
      may serve as potential indicator organisms for monitoring antibiotic tolerance
      among indigenous bacterial populations in various aquatic environments.

PMID- 11249033
TI  - A definition of "social environment".

PMID- 11249034
TI  - Treatment of pancreatic cancer with a combination of docetaxel, gemcitabine and
      granulocyte colony-stimulating factor: a phase II study of the Greek Cooperative
      Group for Pancreatic Cancer.
AB  - PURPOSE: To evaluate the tolerance and efficacy of front-line docetaxel plus
      gemcitabine treatment in patients with inoperable pancreatic cancer. PATIENTS AND
      METHODS: Fifty-four patients with locally advanced or metastatic pancreatic
      cancer were enrolled. Gemcitabine (1000 mg/m2) was administered on days 1 and 8
      and docetaxel (100 mg/m2) on day 8, every three weeks; rh-G-CSF (150 ig/m2 s.c.)
      was given prophylactically on days 9-15. RESULTS: Seven (13%) patients achieved
      partial response and 18 (33%) stable disease (intent-to-treat). The median
      duration of response was 24 weeks, time to tumour progression 32 weeks, and
      overall survival 26 weeks. Performance status was improved in 33% of patients,
      pain in 43%, asthenia in 16%, weight gain in 28% and appetite in 27%. Grade 3-4
      neutropenia occurred in 17 (31%) patients and grade 3-4 thrombocytopenia in four
      (4%). Six (11%) patients developed febrile neutropenia and one of them died from
      sepsis. CONCLUSIONS: This combination is a relatively well-tolerated out-patient
      regimen for patients with inoperable pancreatic cancer.

PMID- 11249035
TI  - Cyclophosphamide, adriamycin and dexamethasone (CAD) is a highly effective
      therapy for patients with advanced multiple myeloma.
AB  - BACKGROUND: Patients with advanced multiple myeloma (stage III or progressive
      myeloma) received the CAD protocol every three weeks: cyclophosphamide 200 mg/m2
      i.v./orally days 1-4, adriamycin 30 mg/m2 i.v. on day 1 and dexamethasone 40 mg
      p.o. days 1-4. PATIENTS AND METHODS: Forty-six patients with a median age of
      sixty years (range 34-84 years) were enrolled. According to Durie-Salmon 44
      patients were in stage III, 2 in stage II; 6 patients had renal insufficiency
      (stage B). Twenty-three patients were pre-treated at least with
      melphalane/prednisone. RESULTS: Remission rates were as follows: complete
      remission 4%, partial remission 70%, minimal change 11%, no change 11%,
      progressive disease 4%. After an observation time of 14 months the median
      progression free interval for 33 patients not treated with subsequent high-dose
      chemotherapy with stem-cell support was more than 14 months. Overall, treatment
      was well tolerated. After 209 cycles given febrile neutropenia occurred in 11% of
      cycles including one fatal outcome. Neutropenia or thrombocytopenia grade 3-4 WHO
      was recorded in 18% and 6% of the cycles, respectively. CONCLUSIONS: This study
      shows that CAD is an effective regimen with an overall remission rate of 74%. The
      CAD protocol should be further evaluated in prospective trials.

PMID- 11249037
TI  - Paraneoplastic pemphigus as the initial presentation of chronic lymphocytic
      leukemia.
AB  - The case history of a 61-year-old male patient is described, who presented with
      severe stomatitis, conjunctivitis and leukocytosis. The diagnosis chronic
      lymphocytic leukemia (CLL) stage A (0) was made, for which no treatment was
      necessary. Progression of stomatitis and conjunctivitis and erythosquamous skin
      lesions with bullae and vesiculae formation developed. Under the diagnosis of
      bullous pemphigoid the patient was treated with corticosteroids. The histologic
      and immunofluorescence examination of a skin biopsy was compatible with this
      diagnosis, and antibodies to skin could not be detected in a first serum sample.
      Pseudomonas was cultured from all lesions, the corticosteroids were stopped and
      antibiotic treatment was started, without clear effect. Because of progression of
      skin lesions and debilitation, the patient finally declined all treatment and
      died five weeks after admission. Post-mortem examination showed enlarged
      lymphnodes in the cervical, aortal en iliacal areas, with histology confirming
      the diagnosis of CLL. Indirect immunofluorescence with the second serum sample
      showed auto-antibodies in high titer directed against the intercellular
      epithelial substance. Immunoblot studies showed binding with the classic target
      antigens in paraneoplastic pemphigus. Re-examination of the histologic skin
      specimen and the result of direct immunofluorescence were in retrospect
      compatible with the diagnosis of paraneoplastic pemphigus.

PMID- 11249038
TI  - The effect of increasing topotecan infusion from 30 minutes to 4 hours on the
      duration of exposure in cerebrospinal fluid.
AB  - BACKGROUND: The development of metastatic disease throughout the neuroaxis from
      primary central nervous system (CNS) tumors and non-CNS tumors suggests the
      cerebrospinal fluid (CSF) is an important source of exposure for chemotherapeutic
      agents. In non-human primates, a 4-hour, as compared to a 30-minute, topotecan
      (TPT) infusion prolonged TPT exposure in the CSF. PATIENT AND METHODS: We
      evaluated this approach in a 51-year-old woman with breast cancer metastatic to
      the CNS. TPT was administered at 1.5 mg/m2/day (cycle 1) and 1.0 mg/m2/day
      (cycles 2 and 3) as a 30-minute infusion on days 0-4, and as a 4-hour infusion on
      day 5. Cycles were repeated every 21 days. Plasma, lateral ventricular CSF, and
      lumbar CSF samples were obtained after 30-minute and 4-hour infusions, and
      assayed for TPT lactone and total by HPLC. A three-compartment model was used to
      calculate area under the plasma (AUCplasma) and lateral ventricular CSF (AUCCSF)
      concentation-time curves. TPT CSF penetration was calculated as the ratio of
      AUCCSF to AUCplasma. RESULTS: Mean +/- SD values for TPT total CSF penetration in
      lateral CSF after 30-minute and 4-hour infusions were 0.25 +/- 0.15 and 0.29 +/-
      0.02, respectively. TPT total lumbar CSF concentration was 3-fold greater after a
      4-hour as compared to a 30-minute infusion. For TPT lactone and TPT total, time >
      1 ng/ml in lateral CSF was 1.8- and 1.7-fold greater, respectively, for a 4-hour
      as compared to a 30-minute infusion. CONCLUSIONS: Prolonging TPT infusion from 30
      minute to 4 hours increases the duration of exposure in the CSF. This study
      demonstrates the ability to develop treatment strategies of systemically
      administered chemotherapy to enhance cytotoxic exposure in the CSF.

PMID- 11249036
TI  - Clearing of cells bearing the bcl-2 [t(14;18)] translocation from blood and
      marrow of patients treated with rituximab alone or in combination with CHOP
      chemotherapy.
AB  - PURPOSE: Patients who were PCR-positive for B-cell leukemia-lymphoma 2 (bcl-2)
      gene rearrangement [t(14;18)] were evaluated for responses to rituximab alone or
      combined with CHOP. PATIENTS AND METHODS: Patients had relapsed or refractory low
      grade or follicular non-Hodgkin's lymphoma (IWF: A-D). The single-agent trial
      used 375 mg/m2 weekly x 4; combination therapy included six cycles of CHOP and
      six 375 mg/m2 infusions of rituximab. Bcl-2 analyses of bone marrow (BM) and
      peripheral blood (PB) samples at base-line and following therapy were performed
      using a PCR assay. RESULTS: In the single-agent trial, of 70 patients whose
      peripheral blood (PB) was bcl-2 positive at baseline, 36 became bcl-2-negative,
      13 remained positive, and 21 varied between positive and negative. The overall
      response rates (ORRs) were 72%, 31%, and 57%, respectively. Twelve of twenty-two
      patients with repeat bone marrow (BM) samples were bcl-2-negative three months
      post-treatment. Of 18 patients in the combination trial, 8 were bcl-2 positive in
      PB and/or BM. All of seven patients positive in PB at baseline and six of seven
      patients positive in BM were negative at the end of therapy; all patients
      responded to treatment (100% ORR). CONCLUSIONS: Rituximab, alone or combined with
      CHOP, eradicated bcl-2 positive cells from PB and BM in over half of the patients
      treated and was associated with a high overall clinical response rate. The impact
      on disease-free and overall survival awaits long-term follow up.

PMID- 11249040
TI  - Adjuvant treatment of colorectal cancer at the turn of the century: European and
      US perspectives.
AB  - BACKGROUND: Despite early scepticism, several studies of systemic adjuvant 5
      fluorouracil (5-FU)-based chemotherapy demonstrated significant benefits in high
      risk colon cancer. As many clinical investigations have since been conducted in
      this setting, a comprehensive literature review was undertaken to clarify the
      role of adjuvant therapy in the treatment of colorectal cancer. DESIGN: Current
      and future adjuvant treatment approaches in colorectal cancer were reviewed, and
      differences in the present-day North American and European practices were
      highlighted. RESULTS AND CONCLUSIONS: 5-FU plus leucovorin for six months is
      generally considered the 'standard' adjuvant treatment in Dukes' stage C (stage
      II) colon cancer. Large-scale international trials of other strategies are
      required to provide further advances in treatment outcome. Following the lead of
      the USA Intergroup trials, a recently initiated cooperative effort, the Pan
      European Trials in Adjuvant Colon Cancer (PETACC), may serve as a European model
      for such investigations. In T3 and/or lymph-node positive rectal cancer,
      postoperative (chemo)radiotherapy in the USA is considered the adjuvant treatment
      of choice. However, most European investigators have advocated for preoperative
      intensive short-course irradiation instead. Randomized trials in this area are
      ongoing. In the near future, new drugs for the treatment of colorectal cancer may
      lead to tailored therapies.

PMID- 11249039
TI  - Reactivation of chronic hepatitis B infection following intensive chemotherapy
      and successful treatment with lamivudine: a case report and review of the
      literature.
AB  - BACKGROUND: Hepatitis B virus reactivation has been reported in cancer patients
      following administration of chemotherapy or immunosuppressive therapy and may
      result in liver damage of varying degrees of severity. Although treatment is
      supportive in nature, lamivudine, a nucleoside analogue has been found to
      suppress HBV replication as evidenced by reports of 13 cases in the medical
      literature. PATIENTS AND METHODS: We report a patient who achieved a successful
      outcome with lamivudine following reactivation of HBV during combination
      chemotherapy for non-Hodgkin's lymphoma, and provide a brief overview of the
      literature including the 13 published case reports. RESULTS: Lamivudine therapy
      resulted in clinical improvement as well as in normalization of liver function
      tests and coagulation profile. CONCLUSIONS: Lamivudine has been found to suppress
      HBV replication manifested both by histology and serum HBV-DNA levels in chronic
      carriers of HBV who developed reactivation of hepatic disease following
      chemotherapy. Physicians caring for such patients should be able to recognize
      this clinical challenge, and lamivudine should be considered.

PMID- 11249041
TI  - Costs of autologous stem-cell transplantation in solid tumours.

PMID- 11249042
TI  - Generalised seizures following ondansetron.

PMID- 11249044
TI  - L'argent n'a pas d'odeur.

PMID- 11249043
TI  - Idiosyncratic reaction after oxaliplatin infusion.

PMID- 11249045
TI  - Retreatment of patients with the same chemotherapy: implications for clinical
      mechanisms of drug resistance.
AB  - BACKGROUND: Patients who relapse after adjutant chemotherapy, or after attaining
      remission following treatment of advanced disease, are sometimes retreated with
      the same type of chemotherapy. The objective of the current review of published
      reports was to assess the probability of response to retreatment, and to examine
      evidence for transient rather than stable forms of clinical drug resistance.
      METHODS: A Medline review of published clinical series where patients were
      retreated with the same chemotherapy that they had received previously. RESULTS:
      We located 15 reports of patients with advanced disease who were retreated with
      the same chemotherapy following complete remission and subsequent relapse, and
      three reports where patients received the same chemotherapy that was given
      previously as adjuvant treatment for breast cancer. For patients with advanced
      disease the median time off-treatment was 48 weeks; response rates to retreatment
      using appropriate criteria were in the range of 18%-100% (median 51%), with a
      substantial proportion of second complete responses. For patients retreated after
      adjuvant chemotherapy for breast cancer the median interval between treatments
      was 84 weeks and the response rates were in the range of 40%-51%. CONCLUSIONS:
      With the caveat that this type of review is subject to publication bias,
      retreatment of patients who relapse after complete response to initial therapy,
      or after adjuvant therapy, is associated with a substantial probability of
      response. Together with evidence that more prolonged or intensive initial therapy
      rarely leads to more frequent or more prolonged responses, the current review
      suggests that some patients may develop transient resistance to chemotherapy.

PMID- 11249046
TI  - 18FDG-PET following treatment as valid predictor for disease-free survival in
      Hodgkin's lymphoma.
AB  - PURPOSE: The value of 18FDG-PET to predict the outcome after therapy in Hodgkin's
      lymphoma was compared to morphologic staging and ESR. PATIENTS AND METHODS: A
      total of 50 concurrent 18FDG-PET and CT studies were performed in 37 patients
      with Hodgkin's lymphoma. ESR was evaluated 32 times after treatment was
      completed. RESULTS: Out of 39 residual masses found by CT 8 relapses could be
      proven. Out of 11 CT exams with CR 3 relapses occurred. CT turned out to show a
      sensitivity, specificity, PPV, NPV, and accuracy of 72%, 21%, 21%, 73%, and 32%,
      with respect to predict disease-free survival (DFS). 18FDG-PET was positive in 22
      examinations with 10 recurrences in this group. Out of 28 negative 18FDG-PET 1
      relapse developed 3 years later. 18FDG-PET turned out to show promising
      sensitivity, specificity, PPV, NPV, and accuracy of 91%, 69%, 46%, 96%, 74%, with
      respect to predict DFS. ESR was elevated in 12 studies of which 5 relapses could
      be proven, while out of 20 normal ESR-studies 3 relapses occurred. Thus, ESR
      turned out to show sensitivity, specificity, PPV, NPV, and accuracy of 63%, 71%,
      42%, 85%, and 75%, with respect to predict DFS. In summary, only 18FDG-PET was
      able to predict DFS statistically significant. CONCLUSION: 18FDG-PET can be very
      useful in patients with residual masses after treatment.

PMID- 11249047
TI  - A real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR)
      to detect breast carcinoma cells in peripheral blood.
AB  - BACKGROUND: The detection of occult carcinoma cells in patients with breast
      cancer has been shown to predict disease recurrence and metastasis. MATERIALS AND
      METHODS: To improve on molecular detection of breast carcinoma cells in blood, we
      have developed a sensitive and quantitative assay using real-time quantitative RT
      PCR identifying transcripts of the cytokeratin-19 (CK19) gene. RESULTS: This real
      time quantitative RT-PCR is sensitive, accurate and has a high reproducibility
      within a wide dynamic range, which permits simultaneous quantitative analysis of
      samples with varying input concentrations. Furthermore, the procedure offers
      several technical advantages over classic quantitative PCR methods (competitive
      RT-PCR, Northern blotting) such as decreased likelihood of contamination due to
      absence of post-PCR manipulations, high sample throughput because of absence of
      post-PCR processing time (no agarose gel electrophoresis). In this pilot study,
      we detected significantly elevated CK19 transcript levels in < 10% of the
      volunteers, in +/- 30% of stage I-IIIa patients preoperatively and in > 70% of
      the and stage IV breast cancer patients. CONCLUSIONS: Analyses using this real
      time quantitative RT-PCR for CK19 mRNA may prove to have clinical implications in
      the assessment of circulating tumour cells in peripheral blood, micrometastases
      in bone marrow or lymph nodes in breast cancer patients. Application of this
      technique in a clinical population may improve diagnosis and monitoring of
      metastatic breast cancer and its validation is currently ongoing.

PMID- 11249048
TI  - Combination chemotherapy with docetaxel and cisplatin for locally advanced and
      metastatic gastric cancer.
AB  - BACKGROUND: Poor treatment results obtained with palliative chemotherapy for
      advanced gastric cancer indicate the need for new effective and well-tolerated
      regimens. PATIENTS AND METHODS: Forty-three patients with locally advanced or
      metastatic gastric cancer were enrolled in a phase II study to evaluate the
      efficacy and safety of combination chemotherapy with doxetacel 75 mg/m2 and
      cisplatin 75 mg/m2 given every three weeks. RESULTS: Thirty-nine patients were
      evaluable for response. Four achieved a complete response and twelve a partial
      response, for an overall response rate of 37.2% (16 of 43 patients; 95%
      confidence interval (CI): 22.98-53.72). Median time to progression was 6.1 months
      and median overall survival 10.4 months. Forty-two percent of all patients were
      still alive at one year and twelve percent at two years. The major toxicity was
      leukopenia which reached grade 3-4 in 18.6% (n = 8) of the patients. However, no
      febrile neutropenia occurred. Non-haematological toxicities were usually mild to
      moderate. Grade 3 toxicities included diarrhea (9% of the patients), nausea and
      vomiting (7%), and alopecia (7%). Severe ototoxicity with or without peripheral
      neuropathy developed after completion of chemotherapy in two patients.
      CONCLUSIONS: These results suggest that the combination of docetaxel and
      cisplatin has moderate toxicity and is an effective regimen for the treatment of
      advanced gastric cancer, both with regard to response rate and survival.

PMID- 11249049
TI  - Primary intestinal diffuse large B-cell non-Hodgkin's lymphoma: clinical
      features, management, and prognosis of 66 patients.
AB  - BACKGROUND: In Saudi Arabia, primary gastrointestinal non-Hodgkin's lymphoma
      (NHL) is common. Recently we have reported one of the largest series of primary
      gastric (PG) diffuse large B-cell lymphoma (DLCL). This has prompted the analysis
      of another series of patients with primary intestinal DLCL to depict the clinical
      features and the outcome of that disease and to compare those with that for PG
      involvement. PATIENTS AND METHODS: The data of 66 adult patients with primary
      intestinal NHL having DLCL histology were retrospectively reviewed. RESULTS:
      Patients had a median age of 45 years. Of 64 treated patients, 16% and 84%,
      received single and multiple modality treatment, respectively. Seventy-six
      percent, ten percent, and fourteen percent attained complete remission (CR),
      partial remission (PR), and no response/progressive disease, respectively.
      Multivariate analysis failed to identify any variable that predict the likelihood
      of attaining CR. Over a median follow-up of 81 months for all 66 patients, 32
      (48%) were alive and disease-free, 5 (8%) were alive with evidence of disease,
      and the remaining 29 (44%) were dead. The median overall survival (OS) was 101
      months and it was 58% (+/- 6%) and 48% (+/- 7%) at 5- and 10-year, respectively.
      Of the 54 patients who achieved CR or PR, the median event-free survival (EFS)
      was not reached, but the predicted 5- and 10-year EFS was 61% (+/- 7%) and 52%
      (+/- 7%), respectively. Only low serum albumin (<30 g/l) was associated with
      adverse OS and EFS in a univariate analysis, however, multivariate analysis was
      not possible. Our analysis showed that compared with single-modality management,
      multi-modality strategy attained significantly higher CR, and advantageous EFS,
      but without a significant superior effect on OS. In comparison with patients with
      PG DLCL, those with primary intestinal disease demonstrated more adverse
      prognostic features, but had an equivalent survival. CONCLUSIONS: This series
      characterized the clinico-pathologic features and outcome of patients with
      primary intestinal DLCL. While surgical resection in primary intestinal NHL seems
      beneficial, only prospective randomized studies can ascertain its precise role.
      Compared with patients with PG NHL, patients with primary intestinal disease had
      more prevalence of adverse prognostic features.

PMID- 11249050
TI  - Results of a phase III study of early versus delayed whole brain radiotherapy
      with concurrent cisplatin and vinorelbine combination in inoperable brain
      metastasis of non-small-cell lung cancer: Groupe Francais de Pneumo-Cancerologie
      (GFPC) Protocol 95-1.
AB  - PURPOSE: To determine if the timing of whole brain radiotherapy (WBRT) with
      respect to chemotherapy with cisplatin and vinorelbine would influence survival
      in patients with non-small-cell lung cancer (NSCLC) and concurrent brain
      metastasis. PATIENTS AND METHODS: One hundred seventy-six patients with brain
      metastasis from NSCLC were included in the study between July 1995 and October
      1997. All patients received chemotherapy with cisplatin 100 mg/m2 on day 1 and
      vinorelbine 30 mg/m2 on days 1, 8, 15, 22. Cycles were repeated every four weeks.
      Evaluation of response was performed after two, four or six cycles. After two
      cycles, chemotherapy was administered to the responders to a maximum of six
      cycles. Patients were randomised to receive WBRT 30 Gy/10 fx/12 days and delayed
      corticosteroids. (arm A) for the intracranial nonresponders, or early on day 1 to
      12 during the first cycle of chemotherapy (arm B). RESULTS: One hundred seventy
      one patients were eligible: eighty-six in arm A and eighty-five in arm B; none
      had received prior chemotherapy; seventy-six and seventy-three, respectively,
      were assessable for response. There was a 21% overall objective response rate
      (OR) (with 1 complete response and 17 partial responses) after two cycles of
      chemotherapy alone (arm A) and a 20% OR (with 17 partial responses) to
      chemotherapy and early WBRT (arm B). The intracranial OR was 27% and 33%,
      respectively (P = 0.12). The six months survival rate (46% and 40%) and the
      median survival duration (24 and 21 weeks, respectively) were not significantly
      different between the two arms (P = 0.83, log-rank test). The major toxicity was
      severe or life-threatening neutropenia (grade 4), which occurred in 35% of arm A
      patients and 36% of arm B patients. There were thirteen treatment-related deaths
      (six in arm A and seven in arm B). There was no difference between the arms for
      haematological and neuro-toxicities. CONCLUSIONS: These results confirm the
      efficacy of chemotherapy in brain metastases of NSCLC and suggest that the timing
      (early or delayed) of WBRT did not influence survival of NSCLC with brain
      metastasis treated with concurrent chemotherapy.

PMID- 11249052
TI  - Two cultures or two faces?

PMID- 11249051
TI  - High-dose thiotepa and melphalan with hemopoietic progenitor support following
      induction therapy with epirubicin-paclitaxel-containing regimens in metastatic
      breast cancer (MBC).
AB  - BACKGROUND: Preliminary data from phase III randomized studies have failed to
      show benefit of HDC given as consolidation after anthracycline and alkylating
      based chemotherapy in metastatic breast cancer (MBC). Moderate activity of
      induction regimens and selection of chemoresistant clones are among the possible
      reasons for these disappointing results. We therefore have designed a phase II
      study where high-dose alkylating agents are given as consolidation after an
      induction treatment including the most active agents (epirubicin and paclitaxel)
      without alkylating agents. PATIENTS AND METHODS: Patients with MBC not previously
      treated with chemotherapy for metastatic disease were eligible. After six courses
      of epirubicin-paclitaxel +/- gemcitabine patients received a course of thiotepa
      600 mg/m2 + melphalan 160 mg/m2 with hemopoietic support. Pharmacokinetic
      parameters of thiotepa and melphalan were measured and related to treatment
      outcomes. The L-VEF of the patients was monitored before and after treatment.
      RESULTS: Forty-eight patients have been treated. Before HDC 14 patients were in
      CR, and 34 in PR. A median of 6.92 x 10(6) (range 1.53-16.6) CD34+ cells/kg were
      reinfused after HDC. Median days (range) to neutrophils > 0.5 x 10(9)/l and
      platelets > 20,000 x 10(9)/l were 9.5 (9-33) and 10 days (9-32), respectively.
      Symptomatic CHF was observed in two patients (4.1%). Cmax and AUC of thiotepa
      showed a linear relationship with time to progression (TTP) and overall survival
      (OS): r2 = 0.6. After HDC the conversion rate from PR to CR was 44.1%. At five
      years progression-free and overall survival rates are 37.5% and 65%,
      respectively. A treatment-related death was observed. CONCLUSIONS: High-dose
      thiotepa and melphalan after an epirubicin-paclitaxel-containing treatment is
      feasible, devoid of significant cardiotoxicity and very active. Pharmacokinetic
      parameters of high-dose thiotepa might be linked to treatment outcome.

PMID- 11249053
TI  - Metalloproteinase expression and prognosis in soft tissue sarcomas.
AB  - BACKGROUND: Degradation of extracellular matrix by tumor-associated proteases can
      promote cell invasion and metastasis. This study assessed the prognostic role of
      MMP2, MMP9 metalloproteinases, and of the metalloproteinase inhibitor TIMP2,
      related to disease-free survival (DFS), in soft tissue sarcoma (STS) patients.
      MATERIALS AND METHODS: Level and distribution of MMP2, MMP9, and TIMP2 expression
      were evaluated on 73 biopsies by immunohistochemistry and immunoblotting.
      Biopsies included 29 liposarcomas, 29 synovial sarcomas, and 15 malignant
      peripheral nerve sheath tumors (MPNST). Association between DFS and overall
      survival with different variables was assessed. RESULTS: In terms of DFS,
      increased MMP2 reactivity and lack of TIMP2 expression were significant for poor
      prognosis in all samples (P = 0.0005 and P = 0.006 respectively). MMP2 correlated
      to histologic grade (P = 0.005). Lack of TIMP2 expression was a poor prognostic
      factor for DFS in synovial sarcoma (P = 0.009), while MMP2 and MMP9 correlated
      with metastasis (P = 0.008 and P = 0.005, respectively) and grade (P = 0.001 and
      P = 0.04 respectively) in liposarcoma. CONCLUSIONS: These prognostic markers that
      influence growth and spread of tumor cells might be useful to define tumor
      aggressiveness and risk of the metastasic event.

PMID- 11249054
TI  - Prognostic factors and long-term survival in 585 patients with metastatic breast
      cancer treated with epirubicin-based chemotherapy.
AB  - BACKGROUND: Analysis of prognostic factors in patients with metastatic breast
      cancer treated with epirubicin-based chemotherapy. PATIENTS AND METHODS: Data
      from 469 patients treated with epirubicin-based chemotherapy for metastatic
      breast cancer were used. Prognostic factors were identified (Cox multivariate
      analysis). A prognostic index was compiled and risk groups were established
      accordingly. The applicability of the index was investigated in a series of 116
      patients. RESULTS: The prognostic factors identified were: liver, pleural, soft
      tissue, lung and bone metastases, performance status > 2, advancing age, abnormal
      elevation of serum lactate dehydrogenase and negative/unknown oestrogen receptor
      status. Four risk groups were established: good, intermediate I, intermediate II
      and poor. The median and five-year survivals in percentage were: good: 34 months
      (26%); intermediate I: 19 months (6%), intermediate II: 12 months (0%); poor: 7
      months (1%). The corresponding values in the applicability group were: 32 months
      (23%); 28 months (22%); 18 months (5%); and 6 months (0%). CONCLUSIONS: It is
      more the number and impact on the organs involved, that predict the patients'
      survival. The construction of a prognostic index could be helpful in assessing
      the outlook for patients, especially the quite dramatic difference in long-term
      survival between the good and poor risk patients.

PMID- 11249055
TI  - Second-line chemotherapy for non-small-cell lung cancer with monthly docetaxel
      and weekly gemcitabine: a phase II trial.
AB  - BACKGROUND: Docetaxel and gemcitabine are active against chemotherapy-pretreated
      non-small-cell lung cancer (NSCLC). The purpose of this phase II study was to
      evaluate the efficacy and safety of monthly docetaxel combined with weekly
      gemcitabine in NSCLC patients failing one prior regimen. PATIENTS AND METHODS:
      Forty patients were enrolled. Prior chemotherapy was a platinum-based combination
      in 36 patients, using vinorelbine in 26 patients and etoposide in 10 patients.
      The other four patients had prior single agents. Tumors were refractory or
      resistant to front-line therapy in 80% of patients. Treatment was gemcitabine 800
      mg/m2 days 1, 8, 15 and docetaxel 100 mg/m2 day 1, with cycles repeated every
      four weeks. RESULTS: Thirteen patients responded (32.5%; 95% confidence interval
      (CI): 19%-49%), including one complete and 12 partial responses. Responses were
      observed at all metastatic sites, with similar response frequencies in platinum
      sensitive and platinum-resistant/refractory tumors. The median time to
      progression for responders was nine months, with two responses lasting longer
      than a year. Median survival was 8.1 months. Hematologic toxicities included
      grade 4 neutropenia in 23 patients, with 4 episodes of febrile neutropenia, grade
      3-4 thrombocytopenia in 9 patients, and anemia requiring red cell transfusions in
      9 patients. With the exception of asthenia, severe non-hematologic toxicities
      were infrequent. CONCLUSIONS: Monthly docetaxel, combined with weekly
      gemcitabine, is an active and safe second-line therapy for NSCLC patients.

PMID- 11249056
TI  - The AJCC staging proposal for cutaneous melanoma: comments by the EORTC Melanoma
      Group.

PMID- 11249057
TI  - Vinorelbine, cisplatin and continuous infusion of 5-fluorouracil (ViFuP) in
      metastatic breast cancer patients: a phase II study.
AB  - PURPOSE: Chemotherapy regimens for patients with advanced breast cancer or large
      primary tumours (including locally advanced disease) usually contain
      anthracyclines, taxanes or both. We investigated a multi-agent regimen for
      patients for whom anthracyclines and/or taxanes may not be suitable. We assessed
      efficacy in terms of response rate and time to progression of a combination with
      continuous infusion 5-fluorouracil (5-FU), vinorelbine and cisplatin (ViFuP
      regimen), as a first or subsequent line treatment for metastatic breast cancer
      patients. PATIENTS AND METHODS: One hundred consecutive patients with advanced
      breast cancer were treated with 5-FU 200 mg/m2 administered continuously through
      a permanent central venous line; vinorelbine was given on days 1 and 3 at a dose
      of 20 mg and cisplatin was administered at 60 mg/m2 on day one. Therapy was given
      every three weeks. The median age was 50 years (range 23-72). Fifty-two patients
      had received prior chemotherapy for metastatic breast cancer, and sixty-one
      percent had previously received anthracyclines, thirty-five percent taxanes and
      twenty-nine percent 5-FU as a bolus injection. All patients were assessable for
      toxicity, four patients were not assessable for response. RESULTS: There were
      four complete responses (4%). Forty-nine patients had a partial response (overall
      response rate, 55%; 95% confidence interval (CI): 45%-65%). After a median follow
      up of 10.2 months, median duration of response is 5.2 months (range 1.5-20.7+
      months), time to progression (TTP) is 6.8 months (range 0.3-24.7 months). Acute
      toxicity, including myelosuppression, was mild: only 18% of patients had grade 4
      granulocytopenia and one patient experienced grade 4 diarrhea. Only 15% of
      patients had any non-hematological grade 3 toxicity including nausea (4%),
      stomatitis (4%), diarrhea (2%), fatigue (1%), fever (1%), photosensitivity (1%),
      hand-foot syndrome (1%). Grade 2 alopecia was observed only in six patients (6%).
      Eleven patients developed a right diaphragmatic supra elevation, while deep vein
      thrombosis, central venous catheter associated, occurred in eight patients.
      CONCLUSIONS: We identified a combination chemotherapy with noteworthy efficacy
      and well tolerated subjectively as either a first- or second-line treatment for
      metastatic breast cancer patients. The regimen warrants further development
      focusing on the comparison with either continuous administration of oral
      fluoropyrimidine derivatives.

PMID- 11249058
TI  - "Dr. P. C. Sen Memorial Best Paper Presentation Award on rural health practice".
      Physical and mental community health: what are the obstacles!
AB  - The present work aims to study the cultural concepts of the health in general and
      mental health in particular from six villages of Sundarban region, West Bengal,
      India, by using field research methodology, viz, participants observation, focus
      group discussion and in depth interview. A qualitative data was collected from
      the field. Analysis of the data shows that there is a clear difference of
      conception among the people of the region according to their socio-economic
      status. Poor and non-educated segment stressed much more on the physical ability
      and lack of economic resources in relation to health, whereas educated and
      comparatively economically stable segment with some urban influence, stressed
      more on both physical and emotional stability as a measure of good health. The
      pattern of help seeking also reflects different preferences towards traditional
      and modern treatment facilities available in the region. Results on the study
      promoted to take intensive community awareness programme for effective health
      coverage of the population.

PMID- 11249059
TI  - A study of intersectoral co-ordination in disaster management in flood prone
      districts of West Bengal.
AB  - Disaster management is essentially a multi-sectoral and multidisciplinary
      endeavor. The status of disaster preparedness, coordination among different
      sectors and its impact on disaster management performance were studied and
      compared in two flood prone comparable districts viz. Midnapore and Murshidabad
      of West Bengal. The perception of state level officers about important job
      responsibilities of other departments in relation to disaster management and its
      intersectoral co-ordination was found mostly satisfactory; but this desired
      status did not prevail at district level. Lack of co-ordination among some
      sectors at district levels persisted in Murshidabad district, indicating
      comparatively better intersectoral co-ordination in Midnapore district. Thus,
      'early response following flood' the most important indicator of adequacy of pre
      disaster preparedness was found significantly better in Midnapore district. On
      the contrary, due to liberal use of Radio transmission set for flood warning, a
      significantly higher proportion of affected families in Murshidabad district
      received early flood warning compared to Midnapore. Organisational aspects of
      disaster management need to be improvised with role clarity of different
      departments in relation to other sectors involved in this endeavor.

PMID- 11249060
TI  - Annual report of secretary general for the period from 1st October, 1997 to 31st
      December, 1998.

PMID- 11249061
TI  - Has treatment for childhood diarrhoea changed?

PMID- 11249062
TI  - National meet on environment & health: challenges for the 21st century.

PMID- 11249063
TI  - Dr. K. N. Rao Memorial Oration. Environment and health: challenges of the new
      millennium.

PMID- 11249064
TI  - An improved clinical model of orthotopic pancreatic cancer in immunocompetent
      Lewis rats.
AB  - The study of pancreatic cancer (PaCa) requires orthotopic, clinically relevant
      animal models. The aims of this study were to establish an orthotopic model of
      ductal pancreatic adenocarcinoma in immunocompetent Lewis rats and to develop a
      scoring system to quantify local tumor infiltration and distant metastasis. Cells
      (10(7)) of the rat ductal PaCa cell line DSL-6A/C1 were injected s.c. into donor
      rats. After 8 weeks, either three (IPL-3) or five (IPL-5) fragments (1 mm3) of
      the resulting s.c. tumors were microsurgically implanted into the pancreas of
      recipient rats. In another series of animals, 10(7) DSL-6A/C1 cells were directly
      injected (INJ) into the pancreas. All animals were monitored daily until death or
      for 16 weeks. At autopsy, volume of primary tumors and ascites, local and
      systemic tumor spread, and histologic phenotype were assessed. IPL-5 resulted in
      significantly larger tumors (12,224 +/- 1,933 mm3), more local infiltration and
      systemic spread (score: 18.3 +/- 2.0 points), severe clinical tumor disease, and
      lethality (50%) in comparison to the other induction techniques (IPL-3: 283 +/-
      115 mm3/3.5 +/- 0.8 points/0; INJ: 752 +/- 207 mm3/4.3 +/- 0.8 points/8%).
      Histologic examination revealed moderately to well-differentiated ductal tumors,
      surrounded by dense stroma. Intraperitoneal tumor dissemination in the INJ group
      occurred simultaneous with primary tumor growth, indicating PaCa cell spread
      during injection. Orthotopic implantation of five DSL-6A/C1 tumor fragments into
      the rat pancreas provides a valid clinical model of ductal pancreatic
      adenocarcinoma in immunocompetent rodents for preclinical treatment studies. The
      dissemination score we used permitted quantification of local and systemic tumor
      spread.

PMID- 11249065
TI  - Expression of neural cell adhesion molecule in pancreatic cancer.
AB  - Neural cell adhesion molecule (NCAM) has been found to be a significant factor
      for survival in various solid tumors. In the present study, we examined the
      expression of NCAM in exocrine tumors of the pancreas by immunohistochemistry,
      using two monoclonal antibodies against NCAM and polysialic acid (MAB735).
      Expression of NCAM was seen mainly in the cytoplasm of the following cells:
      regenerating duct cells among neoplastic tissue, hyperplastic islet cells,
      intrapancreatic nerves and ganglia, as well as tumor cells. There was no
      reactivity with MAB735. We found a significant correlation between intense NCAM
      expression (i.e., expression in more than 50% of all tumor cell mass) and
      survival rates in tubular adenocarcinoma, particularly moderately differentiated
      tumors (p < 0.05). There was no statistically significant relation between NCAM
      reactivity and tumor stage or any of the clinicopathologic parameters described
      by the Japan Pancreas Society (p > 0.05). We conclude that the expression of NCAM
      in tubular adenocarcinoma of the pancreas, particularly in moderately
      differentiated tumors, has a significant impact on the overall patient survival.

PMID- 11249066
TI  - Expression of clusterin in pancreatic acinar cell injuries in vivo and in vitro.
AB  - Clusterin is a secretory glycoprotein that is highly induced in several tissues
      in response to injury. The pathophysiologic significance of clusterin in the
      pancreas remains largely unknown. The aim of this work was to examine whether
      clusterin is expressed in spontaneous chronic pancreatitis in the WBN/Kob rat and
      to investigate the relationship between clusterin and apoptosis in pancreatic
      acinar AR4-2J cells. In the in vivo study, 4-week-old male WBN/Kob rats developed
      chronic pancreatitis at 12 weeks. Clusterin mRNA was expressed after 12 weeks and
      then decreased. Immunohistochemistry showed clusterin expression in the acinar
      cells. In the in vitro study, clusterin mRNA and protein were strongly induced in
      AR4-2J cells treated either with arginine, menadione, tumor necrosis factor-alpha
      or transforming growth factor-beta1. In the time course study with arginine or
      menadione, clusterin mRNA was expressed after 4 hours and peaked at 8 and 24
      hours, whereas DNA fragmentation peaked at 72 hours. Our results show that
      clusterin is overexpressed in the pancreas at the onset of chronic pancreatitis
      in vivo and in cultured acinar cells in response to various stimuli in vitro,
      suggesting that clusterin is a defense mechanism of the exocrine pancreas.

PMID- 11249067
TI  - Characterization of secretory and morphologic properties of primary cultured
      endocrine cells from porcine pancreata.
AB  - We characterized morphologic and secretory properties of porcine pancreatic
      endocrine cells in primary culture obtained by autolytic preparation without any
      exogenous proteolytic enzymes. The endocrine cells exhibited a neuron-like shape,
      and insulin granules were accumulated at the terminal of the processes. Thus
      derived endocrine cells survived in culture medium containing nicotinamide and
      remained sensitive to glucose for at least 6 weeks after preparations. The cells
      responded well to physiologic concentrations of glucose, and high K+
      depolarization and the antidiabetic sulfonylureas, tolbutamide, and glibenclamide
      also elicited the release. With high glucose, insulin release was markedly
      potentiated by forskolin, glucagon, glucagon-like peptide-1, and arginine and
      inhibited by somatostatin, the Ca2+ channel blocker nitrendipine, and the ATP
      sensitive K+ channel opener diazoxide. Epinephrine had dual effects on the
      release by glucose; enhanced within a low nanomolar range and inhibited at 1
      micromol/L. However, the cells were unresponsive to leucine. Such secretory
      sensitivities to nutrients, hormones, and pharmacologic agents, and long survival
      rate (as long as 5-6 weeks) of these cells suggest to us therefore that derived
      endocrine cells may be useful for xenotransplantation of pancreatic beta cells
      for treatment of insulin-dependent diabetes mellitus.

PMID- 11249068
TI  - ARIP cells as a model for pancreatic beta cell growth and development.
AB  - Pancreatic ductal epithelium contains the pluripotent cells that develop into
      pancreatic beta cells. However, little is known about intrinsic or extrinsic
      factors that enable this differentiation to occur. PDX-1 plays a critical role in
      pancreatic development and insulin secretion. Therefore we transfected the PDX-1
      gene into ARIP cells, a rat pancreatic ductal cell line. The ARIP and ARIP/PDX-1
      cells were treated with known growth and differentiation factors including
      hepatocyte growth factor, activin A, betacellulin, reg, INGAP, nicotinamide, and
      retinoic acid. Despite the ductal origin of these cells, no changes in expression
      of 24 pancreatic genes, as determined by semiquantitative reverse transcription
      polymerase chain reaction (RT-PCR), occurred in either cell line. Western blot
      analysis confirmed the presence of the active phosphorylated form of the PDX-1
      protein. To enhance PDX-1 phosphorylation, we cultured ARIP and ARIP/PDX-1 cells
      in a high-glucose medium; however, as with the other conditions, no differences
      in mRNA expression were noted on the RT-PCR assay. We conclude that other factors
      may be necessary for beta cell differentiation and/or that ARIP cells are a poor
      model of pancreatic development.

PMID- 11249069
TI  - Beta cell adaptation to dexamethasone-induced insulin resistance in rats involves
      increased glucose responsiveness but not glucose effectiveness.
AB  - Islet beta cell adaptation to dexamethasone-induced insulin resistance was
      characterized with respect to glucose-stimulated insulin secretion and islet
      innervation. Male Sprague-Dawley rats were injected daily with dexamethasone (2
      mg/kg for 12 days), which resulted in hyperinsulinemia and hyperglycemia compared
      with controls (which were injected with sodium chloride). Insulin secretion was
      characterized in collagenase-isolated islets. Islet innervation was examined by
      immunocytochemical analysis of tyrosine hydroxylase, neuropeptide Y (sympathetic
      nerves), and vasoactive intestinal polypeptide (cholinergic nerves). In islets
      isolated from the insulin-resistant animals, the insulin response to 3.3 or 8.3
      mM glucose was three times greater during perifusion compared with controls (p <
      0.001). Incubation of islets at 0 to 20 mM glucose revealed a marked leftward
      shift of the glucose dose-response relation after dexamethasone treatment
      (potency ratio, 1.78; p < 0.01), with no difference at 0 or 20 mM glucose. Thus,
      the potency but not the efficacy of glucose was increased. The number of islet
      nerves did not differ between dexamethasone-treated rats and controls.
      Dexamethasone-induced insulin resistance leads to adaptively increased glucose
      responsiveness of the islet beta cells, with increased potency, but not increased
      efficacy, of glucose to stimulate insulin secretion without any evidence of
      altered islet innervation.

PMID- 11249070
TI  - Long-term culture in matrigel enhances the insulin secretion of fetal porcine
      islet-like cell clusters in vitro.
AB  - To study the influence of extracellular matrix (ECM) on isolated fetal porcine
      islet-like cell clusters (ICC), ICC were cultured either embedded in Matrigel
      (MG) or growth factor-reduced Matrigel (MG-GF), or in the absence of matrix for
      20 days. The insulin accumulation in the culture medium was determined every
      fifth day. After culture, the ICC were retrieved and used for acute insulin
      release experiments and subsequently subjected to either determination of DNA and
      insulin contents or immunohistochemistry. It was found that culture in MG and MG
      GF significantly increased both the insulin accumulation in the culture medium
      and the insulin content/DNA compared to culture in the absence of matrix. In
      addition, MG culture significantly increased the insulin output with time
      compared with the initial 5-day value. The acute insulin release was
      significantly higher from the ICC cultured in the presence of matrix, whereas no
      acute glucose-induced insulin response could be detected. During the culture
      period, the ICC cultured in the absence of matrix disintegrated and formed a
      monolayer of cells in the culture dish, whereas the ICC cultured in matrix formed
      rounded structures containing a substantial number of insulin-positive cells. In
      some cases, cyst-like structures could be seen after culture in matrix. The data
      suggest that beta-cell differentiation during fetal development has a dual
      requirement for extracellular matrix components and growth factors.

PMID- 11249071
TI  - Carbachol restores insulin release in diabetic GK rat islets by mechanisms
      largely involving hydrolysis of diacylglycerol and direct interaction with the
      exocytotic machinery.
AB  - In several models of insulin resistance, cholinergically induced insulin
      secretion is augmented. We studied here whether this also is present in the
      spontaneously diabetic GK (Goto-Kakizaki) rat pancreas. Using carbachol (50
      micromol/L), enhanced insulin release was elicited in perfused pancreas under
      normal or depolarized conditions in GK compared with control rats at 3.3 mmol/L
      glucose (p < 0.03). Carbachol fully normalized insulin secretion in GK rats at
      16.7 mmol/L glucose through an effect abolished by atropine. Similarly, direct
      stimulation of protein kinase C (PKC) with the DAG-permeable compound 1-oleoyl-2
      acetyl-sn-glycerol (OAG, 300 micromol/L) induced more pronounced insulin release
      in GK islets than in control islets. The diacylglycerol (DAG) lipase inhibitor
      RHC-80267 (35 micromol/L) significantly reduced carbachol effects in control and
      GK islets, but had no effect on OAG-induced insulin release. The enhanced
      insulinotropic effects of carbachol in GK islets was not accompanied by increased
      cyclic adenosine monophosphate (cAMP) or arachidonic acid (AA) formation in GK
      when compared with control islets. In conclusion, cholinergic stimulation induced
      enhanced insulin release in diabetic GK islets. This is largely mediated through
      mechanisms involving hydrolysis of DAG to AA and interaction with exocytotic
      steps of insulin release.

PMID- 11249072
TI  - Impaired hepatocyte glucose transport protein (GLUT2) internalization in chronic
      pancreatitis.
AB  - Chronic pancreatitis (CP) is associated with impaired glucose tolerance and with
      reduced hepatic sensitivity to insulin. We have previously shown that in normal
      and sham-operated rats, insulin suppresses hepatic glucose production, and this
      suppression is associated with a decrease in the hepatocyte plasma membrane-bound
      quantity of the facilitative glucose transport protein GLUT2. The insulin
      mediated reduction in membrane-bound GLUT2 is impaired in CP, and may play a role
      in the glucose intolerance associated with CP. To determine whether GLUT2 is
      actively internalized and whether this mechanism is disordered in CP, livers from
      fed and fasting rats in whom CP had been induced 2-3 months earlier by pancreatic
      duct oleic acid infusion, and in sham-operated (sham) rats, were fractionated to
      yield endosome (E)- and plasma membrane (PM)-enriched fractions. Forty-five
      minutes after duodenal intubation alone (fasting) or intubation plus duodenal
      feeding, livers were removed, homogenized and ultracentrifuged, and microsomal
      pellets were separated by sucrose density gradient ultracentrifugation. GLUT2
      content of fractions was determined by Western blotting and scanning
      densitometry. The E:PM ratio of GLUT2 increased from 0.68 +/- 0.11 (mean +/- SEM)
      in fasting sham livers (n = 8) to 1.04 +/- 0.09 in fed sham livers (n = 8; p <
      0.05). However, there was no change in the E:PM ratio of GLUT2 in CP livers after
      duodenal feeding (0.90 +/- 0.12 vs. 0.86 +/- 0.10; n = 8,8; p = NS). To test our
      findings using confocal laser scanning microscopy, liver specimens from fed and
      fasting CP and sham rats were minced, fixed in 4% paraformaldehyde, sectioned,
      and stained with rabbit antirat GLUT2 antibody followed by rhodamine-labeled
      secondary antibody. GLUT2 was quantified by mean pixel intensity in an 8 x 16
      pixel area of PM and a 16 x 16-pixel area of cytosol (CYT) in each of 30 random
      cells/field (400x) in each of three rats per group. As in the fractionation
      study, duodenal feeding increased the CYT:PM ratio of GLUT2 from 0.75 +/- 0.01 in
      fasting sham liver to 0.86 +/- 0.01 in fed sham liver (p < 0.0001), while the
      CYT:PM ratio in CP remained unchanged. We conclude that feeding induces a shift
      in GLUT2 from the plasma membrane to the endosomal pool. The feeding-induced
      internalization of GLUT2 is absent in livers from rats with CP and may play a
      role in the glucose intolerance associated with CP.

PMID- 11249073
TI  - Chronic oral administration of protease inhibitor decreases CCK-A receptor mRNA
      expression but increases pancreatic growth in rats.
AB  - It is well-known that chronic oral administration of trypsin inhibitors induces
      pancreatic hypertrophy and hyperplasia via stimulation of endogenous
      cholecystokinin (CCK) release. Because the growth-promoting effect of CCK on the
      pancreas is specifically mediated by the CCK-A receptor, we examined the plasma
      CCK concentrations, the expression of CCK mRNA in the intestine and CCK-A
      receptor mRNA in the pancreas, and pancreatic growth in rats after chronic oral
      administration of synthetic protease inhibitor (PI). PI at a dose of 100 mg/kg
      body weight was administered via an orogastric tube once daily for 20 days.
      Plasma CCK concentrations at 24 hours after the first PI administration were
      significantly higher than those in randomly fed rats (6.57 +/- 0.67 pmol/L vs
      4.31 +/- 0.51 pmol/L; p < 0.001), and further increased to 14.24 +/- 1.63 pmol/L
      after PI for 10 days and decreased to 10.05 +/- 0.72 pmol/L after 15 days of PI
      administration. Treatment with PI for 20 days significantly increased the
      pancreatic weight, and the total pancreatic protein and DNA content by 190%,
      290%, and 170%, respectively, when compared to the control rats. Chronic oral
      administration of PI, however, reduced CCK-A receptor mRNA expression in the
      pancreas by 60%. These findings suggest that chronic oral administration of PI
      induces an elevation of endogenous CCK release and stimulates pancreatic growth,
      but down-regulates the biosynthesis of CCK-A receptor at the transcriptional
      level in the pancreas.

PMID- 11249074
TI  - Conformational changes of pancreatitis-associated protein (PAP) activated by
      trypsin lead to insoluble protein aggregates.
AB  - Pancreatitis-associated protein (PAP), a secretory acute-phase protein of the
      pancreatic acinar cell, is highly up-regulated early in acute pancreatitis. PAP
      expression returns to undetectable levels when the pancreas recovers. In the rat,
      three isoforms of PAP are known, all of which are upregulated during acute
      pancreatitis. Their functions remain obscure. Pancreatic stone protein (PSP/reg),
      which shows strong sequence homology to PAP, is secreted into pancreatic juice
      under physiologic and pathologic conditions. PSP/reg is highly susceptible to
      trypsin cleavage at its ARG11-ILE12 bond. Cleavage results in an N-terminal
      undecapeptide and a C-terminal peptide called pancreatic thread protein (PTP).
      PTP forms oligomeric fibrillar structures, which spontaneously sediment in vitro.
      PTP can be found in protein plugs or stones from patients with chronic
      pancreatitis. Rat PAP contains a trypsin cleavage site at the same position as
      PSP/reg. We hypothesize that PAP is susceptible to tryptic cleavage, and that the
      C-terminal cleavage product of PAP spontaneously precipitates at neutral pH. To
      test our hypothesis, we generated and purified recombinant PAP. Here we report
      the production of rat PAP I, II, and III in a yeast expression system using
      Pichia pastoris. We demonstrate in vitro the tryptic cleavage of rat PAP and the
      formation of a spontaneously precipitating peptide, which we call pancreatitis
      associated thread protein (PATP). PATP displays pH-dependent solubility
      characteristics very similar to those of PTP.

PMID- 11249076
TI  - Magnetic resonance cholangiopancreatography in assessing the cause of acute
      pancreatitis in children.
AB  - Magnetic resonance cholangiopancreatography (MRCP) is a new noninvasive method of
      obtaining images of the pancreaticobiliary tract. Recent advances in MR
      technology and image quality have made it easy to diagnose structural
      abnormalities of the pancreaticobiliary tract (SAPBT) in children. To examine the
      usefulness of MRCP in assessing the cause of acute pancreatitis in children, we
      performed MRCP in 16 patients with acute pancreatitis. The study population was
      divided into two groups according to the cause of acute pancreatitis as follows:
      group 1 consisted of seven patients sonographically diagnosed with choledochal
      cysts; and group 2 consisted of nine patients with no obvious cause of acute
      pancreatitis. Non-breath-hold MRCP using the half-Fourier, single-shot, fast spin
      echo imaging method was performed within 7 days after the onset of pancreatitis.
      Abnormal union of the pancreaticobiliary junction was detected in six of seven
      group 1 patients and in one of nine group 2 patients. Pancreatic divisum was
      detected in one patient of group 1, but could not be confirmed in one patient of
      group 2. Dilatation of the main pancreatic duct was detected in one patient of
      group 1 and in three patients of group 2. Our results suggest that MRCP is a
      useful, noninvasive method of identifying and ruling out SAPBT as a cause of
      acute pancreatitis in children with early-stage pancreatitis.

PMID- 11249075
TI  - Increased transforming growth factor beta in pure pancreatic juice in
      pancreatitis.
AB  - Cytokines play an important role in the regulation of inflammation and fibrosis
      in the development of chronic pancreatitis. In this study, transforming growth
      factor beta (TGFbeta), interleukin (IL)-6, IL-10, and tumor necrosis factor alpha
      (TNFalpha) were measured in pure pancreatic juice obtained through pancreatic
      duct cannulation. Twenty patients with chronic pancreatitis were compared with
      six patients thought to be free of pancreatic disease who were undergoing
      endoscopic retrograde cholangiopancreatography for biliary tract disorders.
      TGFbeta was detected in 17 of 20 patients with chronic pancreatitis tested (85%),
      compared with only one patient in the control group (17%). There was no
      measurable amount of IL-10, IL-6, or TNFalpha in any of the pure pancreatic juice
      samples from any of the patients. These data indicate that TGFbeta may play an
      active role in the advancement of pancreatitis by causing local inflammation and
      inducing fibroblasts to secrete collagen. This finding may be relevant in the
      future for identifying patients whose conditions may advance to chronic
      pancreatitis, and blocking the effects of TGFbeta could have therapeutic effects.

PMID- 11249077
TI  - Is CT during arterial portography useful for the preoperative evaluation of liver
      metastases from pancreatic carcinoma?
AB  - We evaluated computed tomography during arterial portography (CTAP) for the
      preoperative evaluation of liver metastases from pancreatic carcinoma. Thirty-one
      patients with invasive ductal carcinoma of the pancreas underwent CTAP for
      evaluation of liver metastasis. Diagnostic accuracy of CTAP was compared with
      that of intravenous contrast-enhanced CT (IVCT). In this series, both CTAP and
      IVCT showed the same diagnostic accuracy for the patients. The sensitivity,
      specificity, positive predictive value, negative predictive value, and overall
      accuracy of both CT examinations for detecting liver metastases were 60% (three
      of five), 100% (26 of 26), 100% (three of three), 93% (26 of 28), and 94% (29 of
      31), respectively. CTAP did not confer any advantage over IVCT for the
      preoperative evaluation of liver metastases from pancreatic carcinoma.

PMID- 11249078
TI  - [11C]methionine positron emission tomography for the evaluation of pancreatic
      exocrine function in chronic pancreatitis.
AB  - Positron emission tomography (PET) can be used for the quantitative analysis of
      amino acid metabolism. The aim of this study was to investigate whether
      pancreatic exocrine function can be evaluated by [11C]methionine PET in chronic
      pancreatitis (CP) patients. Dynamic PET scan of the pancreas and liver was
      performed in eight healthy subjects and seven patients with CP after intravenous
      (i.v.) injection of [11C]methionine. Simultaneously, duodenal juice was collected
      with the background of continuous i.v. administration of secretin (125 ng/kg/h).
      The radioactivity ratio of the pancreas to that of the liver (PLR) was calculated
      by regions of interest (ROI) analysis. Amylase output and bicarbonate
      concentration were measured in the duodenal aspirates. The PLR of CP patients was
      significantly lower than that of healthy subjects at all time points after
      methionine injection. The PLRs at 4.5 minutes (PLR4.5) after methionine injection
      were positively correlated with the amylase output, mean bicarbonate
      concentration, and volume of duodenal aspirates (R = 0.74, 0.69, 0.46). It is
      concluded that [11C]methionine PET would be a noninvasive method for the
      evaluation of exocrine pancreatic function, which may represent total amino acids
      uptake of viable acinar cells in the pancreas.

PMID- 11249079
TI  - Do early symptoms of pancreatic cancer exist that can allow an earlier diagnosis?
AB  - Diagnosis of pancreatic cancer is made late, and prognosis remains extremely
      poor. This study was carried out to investigate whether symptoms exist before
      pain or jaundice that could suggest pancreatic cancer and favor earlier
      diagnosis. The study involved 305 patients with confirmed pancreatic cancer and
      305 controls. All subjects were interviewed personally at least twice about their
      clinical history; pancreatic cancer patients were asked about any disturbances
      before abdominal pain or jaundice. Of the 305 pancreatic cancer patients, 151
      (49.5%) had some prior disturbances, 108 (35.4%) 6 months or less before pain or
      jaundice and 43 (14.1%) more than 6 months before. Among the latter, 14 (4.6% of
      all patients) had had anorexia and/or early satiety and/or asthenia (7-20 months
      before pain or jaundice), 11 (3.6%) had disgust for coffee and/or smoking and/or
      wine (7-20 months before), 14 (4.6%) had diabetes (7-24 months before), and four
      (1.3%) had acute pancreatitis (8-26 months before). Among the controls, the only
      reports of these symptoms were two (0.7%) cases of asthenia (4 and 6 years
      earlier), 22 (7.2%) cases of diabetes (of which only two [0.7%] were diagnosed 7
      24 months before the interview), and one (0.33%) case of acute pancreatitis (10
      years earlier). Apart from acute pancreatitis, all the other differences between
      patients and controls were statistically significant. In approximately 15% of
      patients, disturbances existed more than 6 months before pain or jaundice, which,
      although not specific, could raise suspicion of the possibility of pancreatic
      cancer. These disturbances could represent the one current opportunity for an
      earlier diagnosis in a significant minority of pancreatic cancer patients.

PMID- 11249080
TI  - Percutaneous embolization of the distal pancreatic duct to treat intractable
      pancreatic juice fistula.
AB  - Pseudocysts and post-necrotic collections of the pancreas are sometimes treated
      by percutaneous drainage. In cases of post-necrotic collection, intractable
      pancreatic juice fistula is often formed by disruption of the main pancreatic
      duct in the necrotized region. We radically treated intractable pancreatic juice
      fistulae by selective cannulation into the distal pancreatic duct via the route
      for percutaneous drainage of post-necrotic collections to extinguish the exocrine
      function of the caudal pancreas. We performed this procedure in two patients in
      whom the major pancreatic duct was damaged at the body of the pancreas, which was
      extensively necrotic. Although mild symptoms of acute pancreatitis appeared in
      both patients after the first procedure, they recovered without severe side
      effects. Neither recurrence of pancreatic juice fistulae nor reduction of the
      glucose tolerance was caused by removing the exocrine function of the caudal
      pancreas in either patient 32 and 24 months after treatment, respectively. This
      method is an effective treatment modality with which to treat intractable
      pancreatic juice fistulae with damage of the main pancreatic duct.

PMID- 11249081
TI  - Duodenal necrosis associated with acute pancreatitis.

PMID- 11249082
TI  - Vacuolating toxin of Helicobacter pylori inhibits secretagogue-induced amylase
      secretion from isolated pancreatic acini.

PMID- 11249083
TI  - Near-infrared (NIR) optical spectroscopy characterizes breast tissue hormonal and
      age status.

PMID- 11249084
TI  - Sources of absorption and scattering contrast for near-infrared optical
      mammography.
AB  - RATIONALE AND OBJECTIVES: Near-infrared (NIR) diffuse optical spectroscopy and
      imaging may enhance existing technologies for breast cancer screening, diagnosis,
      and treatment. NIR techniques are based on sensitive, quantitative measurements
      of functional contrast between healthy and diseased tissue. In this study, the
      authors quantified the origins of this contrast in healthy breasts. MATERIALS AND
      METHODS: A seven-wavelength frequency-domain photon migration probe was used to
      perform noninvasive NIR measurements in the breasts of 28 healthy women, both pre
      and postmenopausal, aged 18-64 years. A diffusive model of light transport
      quantified oxygenated and deoxygenated hemoglobin, water, and lipid by their
      absorption signatures. Changes in the measured light-scattering spectra were
      quantified by means of a "scatter power" parameter. RESULTS: Substantial
      quantitative differences were observed in both absorption and scattering spectra
      of breast as a function of subject age. These physiologic changes were consistent
      with long-term hormone-dependent transformations that occur in breast. Instrument
      response was not adversely affected by subject age or menopausal status.
      CONCLUSION: These measurements provide new insight into endogenous optical
      absorption and scattering contrast mechanisms and have important implications for
      the development of optical mammography. NIR spectroscopy yields quantitative
      functional information that cannot be obtained with other noninvasive radiologic
      techniques.

PMID- 11249085
TI  - Evaluation of linear and nonlinear tomosynthetic reconstruction methods in
      digital mammography.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to comparatively evaluate
      digital planar mammography and both linear and nonlinear tomosynthetic
      reconstruction methods. MATERIALS AND METHODS: A "disk" (ie, target)
      identification study was conducted to compare planar and reconstruction methods.
      Projective data using a composite phantom with circular disks were acquired in
      both planar and tomographic modes by using a full-field, digital mammographic
      system. Two-dimensional projections were reconstructed with both linear (ie,
      backprojection) and nonlinear (ie, maximization and minimization) tuned-aperture
      computed tomographic (TACT) methods to produce three-dimensional data sets. Four
      board-certified radiologists and one 4th-year radiology resident participated as
      observers. All images were compared by these observers in terms of the number of
      disks identified. RESULTS: Significant differences (P < .05, Bonferroni adjusted)
      were observed between all reconstruction and planar methods. No significant
      difference, however, was observed between the planar methods, and only a
      marginally significant difference (P < .054, Bonferroni adjusted) was observed
      between TACT-backprojection and TACT-minimization. CONCLUSION: A combination of
      linear and nonlinear reconstruction schemes may have potential implications in
      terms of enhancing image visualization to provide radiologists with valuable
      diagnostic information.

PMID- 11249086
TI  - Comparison of correlated receiver operating characteristic curves derived from
      repeated diagnostic test data.
AB  - RATIONAL AND OBJECTIVES: It is common to administer the same diagnostic test more
      than once to the same set of patients. The purpose of this study was to develop
      two statistical methods for estimating and comparing correlated receiver
      operating characteristic (ROC) curves for data derived from repeated diagnostic
      tests. MATERIAL AND METHODS: Parametric and semiparametric transformation models
      were developed. These estimation methods were illustrated with data from 72
      pigmented lesions suspected of being malignant melanoma. A diagnostic scoring
      system based on asymmetry, border irregularity, color variation, and diameter was
      used repeatedly, with or without a dermoscope. Statistical hypothesis tests were
      conducted to evaluate whether a dermoscope improved the clarity of the lesion
      features in the scoring system. The resulting ROC curves were constructed, along
      with characteristics and summary measures. RESULTS: The areas under the ROC
      curves were 0.885 (parametric method) and 0.893 (semiparametric method) without
      the dermoscope, and 0.916 (parametric) and 0.912 (semiparametric) with the
      dermoscope. The statistical hypothesis tests did not yield statistically
      significant differences between the underlying ROC curves for either estimation
      method. CONCLUSION: The two transformation models yielded similar results for
      estimation and comparison of the ROC curves. Although a dermoscope did not add
      extra information, the scoring system was accurate for diagnosing malignant
      melanoma.

PMID- 11249087
TI  - Use of a decision-analytic model to support the use of a new oral US contrast
      agent in patients with abdominal pain.
AB  - RATIONALE AND OBJECTIVES: The authors performed this study to compare the cost
      and diagnostic abilities of ultrasound (US) performed with and without the use of
      an oral contrast material recently approved by the U.S. Food and Drug
      Administration. MATERIALS AND METHODS: An interactive decision-analytic model was
      constructed to compare US performed with and without contrast material (SonoRx;
      Bracco Diagnostics) for the evaluation of patients with abdominal pain who were
      suspected of having pancreatic disease. The model considered all resources that
      might be used to evaluate a patient suspected of having pancreatic disease (eg,
      US, computed tomography [CT], endoscopic retrograde cholangiopancreatography,
      fine-needle aspiration biopsy, and open biopsy). The literature and an expert
      panel were the clinical data sources. Cost estimates were based on Medicare and
      non-Medicare reimbursements. The primary cost-effectiveness measure was the cost
      to achieve a diagnosis. RESULTS: SonoRx-enhanced US was less expensive than
      unenhanced US ($714 vs $808, respectively, with Medicare costs; $1,612 vs $1,878,
      respectively, with non-Medicare costs) and as effective (0.785 vs 0.782,
      respectively). SonoRx-enhanced US was more cost-effective than unenhanced US
      ($909 vs $1,034, respectively, with Medicare costs; $2,052 vs $2,401,
      respectively, with non-Medicare costs). This relationship was maintained
      throughout extensive sensitivity analyses. CONCLUSION: SonoRx-enhanced US is more
      cost-effective than unenhanced US, primarily because it avoids the need for CT.
      CT may be avoided owing to the higher probability of obtaining optimal US scans
      with oral contrast material.

PMID- 11249088
TI  - Sonography of acute osteomyelitis in rabbits with pathologic correlation.
AB  - RATIONALE AND OBJECTIVES: Ultrasonography (US) has a potential role in the
      diagnosis of osteomyelitis. The purpose of this study was to determine the
      characteristic sonographic features of acute osteomyelitis and correlate them
      with pathologic findings. MATERIALS AND METHODS: An experimental model of acute
      osteomyelitis was produced in the tibiae of 20 rabbits. Daily US and plain
      radiography were performed for 2 weeks. The authors evaluated periosteal
      reaction, subperiosteal fluid collection, and soft-tissue changes seen with US. A
      hypoechoic band and a hyperechoic line lying along the cortex were considered
      positive signs of subperiosteal fluid collection and periosteal reaction,
      respectively. The findings of periosteal reaction were compared for US and
      radiography, and pathologic findings were also correlated. RESULTS: The most
      common sonographic finding was a hypoechoic band along the cortex (21 [75%] of 28
      tibiae), usually associated with a linear periosteal reaction (20 [71%] of 28).
      This juxtacortical abnormal echogenicity corresponded to periosteal elevation
      with loose fibrovascular connective tissue and granulation, associated with
      subperiosteal abscess formation. The periosteal reactions were detected with US
      before they were seen on radiographs. The periosteum showed gradual thickening
      during the disease process. In 50% of infected tibiae, inflammation or abscess
      formation was observed in the surrounding soft tissue. CONCLUSION: US readily
      demonstrates juxtacortical abnormal echogenicity and soft-tissue infection
      related to acute osteomyelitis. The abnormal echogenicity correlated well with
      the pathologic findings of periosteal reaction and subperiosteal abscess.

PMID- 11249089
TI  - Automatic segmentation of mammographic density.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate a completely
      automatic method, based on Kittler's optimal threshold, to estimate breast
      density by using the mammographers' definition. MATERIALS AND METHODS: Thirty-two
      normal, right-craniocaudal-view mammograms of women aged 37-86 years were
      digitized. The whole breast area was segmented by using Kittler's optimal
      threshold procedure, and the dense portions were then segmented by using a
      modified version of Kittler's method. Segmentation results were validated by
      three independent mammographers who provided a signed percentage (in steps of 5%)
      to indicate the difference between their own visual estimation of the dense
      portions and the results obtained with the algorithm. The difference between the
      algorithm measurements and the mammographers' measurements was compared to the
      interobserver differences. RESULTS: A high correlation was found between the
      algorithm measured density and the mammographers' measurements. Spearman
      correlations ranged from 0.92 to 0.95 (P < .001). Algorithm-measured density
      differed from the mammographers' measurements by an average of 6.9% (ie, average
      of the absolute differences). In contrast, mammographers' measurements differed
      between themselves by an average of 5.4%. CONCLUSION: The difference between
      density as measured with the algorithm and as measured by the mammographers is
      similar to the differences observed between mammographers. This algorithm could
      be useful in providing clinically accurate estimates of breast density.

PMID- 11249090
TI  - Thin-section CT evidence of bronchial thickening in children with stable asthma:
      bronchoconstriction or airway remodeling?
AB  - RATIONALE AND OBJECTIVES: The authors performed this study to determine if
      bronchial wall thickening is present in children with moderate to severe asthma
      during periods free from clinical bronchoconstriction. MATERIALS AND METHODS: The
      authors obtained low (radiation) dose thin-section computed tomographic (CT)
      scans in each of 18 control subjects and 21 children with moderately severe but
      stable asthma. Spirometry was performed on all subjects at the time of CT
      scanning. Bronchial wall thickness and bronchial wall area were measured, and the
      percentage wall area (bronchial wall area divided by bronchial cross-sectional
      area) was calculated. The authors performed best-fit regression analysis of wall
      thickness and percentage wall area versus bronchial diameter and qualitative
      analysis of images for bronchial wall thickening. RESULTS: In asthmatic patients,
      the mean percentage of the predicted forced expiratory volume in 1 second was
      0.88 +/- 0.09. The best fit regression line that demonstrated the relationship
      between wall thickness and bronchial diameter for patients with asthma differed
      significantly from that for control subjects (P < .005). The regression line that
      demonstrated the relationship between the percentage wall area and bronchial
      diameter for patients with asthma differed from that of the control subjects when
      bronchial wall thickness measurements were used to calculate the percentage wall
      area (P < .05). Results of qualitative analysis also showed significantly more
      bronchial wall thickening in asthmatic patients than in control subjects (P <
      .001). CONCLUSION: Bronchial wall thickening detected at thin-section CT in
      children with moderately severe asthma cannot be attributed solely to
      bronchoconstriction and may represent airway inflammation or remodeling.

PMID- 11249091
TI  - Preparing medical students for a filmless environment: instruction on the
      preparation of electronic case presentations from PACS.
AB  - RATIONALE AND OBJECTIVES: As the use of picture archiving and communication
      systems (PACS) expands and radiology departments become increasingly filmless, it
      will become increasingly necessary to teach physicians how to use PACS and
      download diagnostic images. The authors developed an instruction method in which
      medical students enrolled in a radiology clerkship were taught how to use the
      PACS, download digital images, and incorporate them into an electronic case
      presentation. The feasibility and potential benefits of this instructional method
      were studied prospectively. MATERIALS AND METHODS: Between June and October 1999,
      all 36 medical students enrolled in Harvard Medical School's core radiology
      clerkship at Massachusetts General Hospital, Boston, were required to give an
      electronic radiology case presentation with images downloaded from the
      departmental PACS. They were taught how to download images, edit them, and then
      import them into PowerPoint software. They were also given access to the hospital
      information system to obtain pertinent clinical information. At the formal
      presentations, the images were displayed with a liquid crystal display (LCD)
      projector. The students were surveyed on the Ist and last days of the clerkship
      regarding their learning experiences. RESULTS: Before the radiology clerkship,
      81% of the students had never given an electronic presentation with computer and
      LCD projector, 83% had no PACS experience, and 56% had no PowerPoint experience.
      All students learned to prepare and deliver electronic presentations of
      radiologic cases downloaded from PACS. Their presentations were informative,
      innovative, and entertaining, and the images were well displayed. The students
      praised the instruction highly and thought their new skills would serve them
      well. CONCLUSION: Teaching medical students how to prepare and deliver electronic
      presentations of radiologic cases downloaded from PACS proved to be very feasible
      and well appreciated by the students.

PMID- 11249092
TI  - Digitizing your hard-copy teaching file with inexpensive, commercially available
      software.

PMID- 11249093
TI  - Minor diterpenes from Persea indica: their antifeedant activity.
AB  - The new diterpenes anhydrocinnzeylanone, garajonone and 2,3
      didehydrocinnzeylanone, and the known anhydrocinnzeylanine, have been isolated
      from Persea indica. The antifeedant activity of these compounds has been
      evaluated showing the importance of the 11-hemiketal group for the antifeedant
      effects of ryanodane diterpenes.

PMID- 11249095
TI  - Secoiridoid constituents from the fruits of Ligustrum lucidum.
AB  - Two secoiridoid glucosides, lucidumosides A and B, as well as six known
      glucosides, oleoside dimethyl ester, ligustroside, oleuropein, nuezhenide,
      isonuezhenide, and neonuezhenide, were isolated from the fruits of Ligustrum
      lucidum. Their structures were elucidated by spectroscopic methods.

PMID- 11249096
TI  - Triterpenoids from Dysoxylum malabaricum.
AB  - Two triterpenes 21R,23R-epoxy-21alpha-ethoxy-24S,25-dihydroxyapotirucall-7-en-3
      one and 24R-acetoxy-3beta,25-dihydroxycycloartane were isolated from the leaves
      of Dysoxylum malabaricum together with eight known compounds lupeone, lupeol.
      sitosterol, dipterocarpol, cycloart-25-ene-3beta,24-diol, 24R,25
      dihydroxycycloartan-3-one, 3beta,24R,25-trihydroxycycloartane and ergosta
      5,24(24(1))-diene-3beta,4beta,20S-triol. The complete 1H and 13C NMR spectral
      assignment of the new apotirucallene triterpenoid has been achieved by 1H-1H
      COSY, HMQC and HMBC experiments.

PMID- 11249094
TI  - Constituents of the essential oil of Cyperus alopecuroides.
AB  - We have investigated the constituents of the essential oil of Cyperus
      alopecuroides. Three new compounds, the hydrocarbon, (-)-eudesma-2,4(15)-11
      triene, the sesquiterpene alcohol (-)-eudesma-3,11-dien-5-ol and the diterpene
      hydrocarbon (-)-dolabella-3,7,18-triene were isolated and their structure
      elucidated.

PMID- 11249097
TI  - Guaiane dimers from Xylopia vielana.
AB  - From the leaves of Xylopia vielana (Annonaceae) the three dimeric guaianes
      vielanin A-C were isolated and structurally elucidated by mass and NMR
      spectroscopy as 1-3. The structure of 1 contains a bridged ring system formed
      probably via a Diels-Alder reaction of two different guaiane monomers. Compounds
      2 and 3 represent symmetric cyclobutanes formally generated from two equal
      guaiane moieties by [2 + 2] cycloaddition.

PMID- 11249098
TI  - Sesquiterpene polyol esters from Tripterygium wilfordii.
AB  - The extract (T(II)) of Tripterygium wilfordii Hook f. afforded four sesquiterpene
      esters: 1beta,2beta,5alpha,8beta,11-pentaacetoxy-4alpha-hydroxy-3alpha(2'
      methylbutanoyl)-15-nicotinoyl-7-oxo-dihydroagarofuran; 1beta,5alpha,11-triacetoxy
      7beta-benzoyl-4alpha-hydroxy-8beta-nicotinoyl-dihydroagarofuran;
      1beta,2beta,5alpha,11-tetraacetoxy-8alpha-benzoyl-4alpha-hydroxy-7beta-nicotinoyl
      dihydroagarofuran; 5alpha-benzoyl-4alpha-hydroxy-1beta,8alpha-dinicotinoyl
      dihydro- agarofuran as well as one other known sesquiterpene ester. Their
      structures were established on the basis of spectroscopic studies.

PMID- 11249099
TI  - Sesqui- and diterpenoids from two Japanese and three European liverworts.
AB  - A new peroxy muurolane-type sesquiterpenoid was isolated from the ether extract
      of the Belgium liverwort Scapania undulata, together with three known ent
      muurolanes. A new lepidozane-type sesquiterpenoid was isolated from the Japanese
      Porella subobtusa together with a known santalane- and two africane-type
      sesquiterpenoids. All structures were determined by means of NMR spectroscopic
      techniques. The chemosystematics of each species are discussed.

PMID- 11249100
TI  - Flavonoids from Ochna integerrima.
AB  - Two biflavonoids namely, 2",3"-dihydroochnaflavone and 2",3"-dihydroochnaflavone
      7"-O-methyl ether, and a flavonoid glycoside, 6-gamma,gamma
      dimethylallyltaxifolin 7-O-beta-D-glucoside were isolated from the leaves of
      Ochna integerrima.

PMID- 11249101
TI  - Anthocyanins from red flower tea (Benibana-cha), Camellia sinensis.
AB  - Three anthocyanins were isolated from the leaves of red flower tea (Benibana
      cha), Camellia sinensis, and their structures were determined by means of
      chemical and spectroscopic analyses. Two are the anthocyanins, delphinidin and
      cyanidin 3-O-beta-D-galactosides, respectively. Whereas the third, delphinidin 3
      0-beta-D-(6-(E)-p-coumaryl)galactopyranoside. The anthocyanins were also
      contained in the flowers of Benibana-cha in different compositions.

PMID- 11249102
TI  - Further isoflavonoid metabolites from Millettia griffoniana (Bail).
AB  - Three new isoflavonoids, griffonianone A (1), B (2) and C (4) were isolated from
      the root bark of Millettia griffoniana, along with the known maximaisoflavone G
      (5) and 7-hydroxy-6-methoxy-3',4'-methylenedioxyisoflavone (6). Their structures
      were assigned on the basis of spectroscopic data and chemical transformations.

PMID- 11249103
TI  - Lignan glucosides from Acanthus ilicifolius.
AB  - From the aerial part of Acanthus ilicifolius, two lignan glucosides, (+)
      lyoniresinol 3a-[2-(3,5-dimethoxy-4-hydroxy)-benzoyl]-O-beta-glucopyranoside, and
      dihydroxymethyl-bis(3,5-dimethoxy-4-hydroxyphenyl) tetrahydrofuran-9(or 9')-O
      beta-glucopyranoside have been isolated, together with eight known compounds. The
      structural elucidations were based on the analyses of physical and spectroscopic
      data.

PMID- 11249104
TI  - A malonylated anthocyanin and flavonols in blue Meconopsis flowers.
AB  - The structures of the major anthocyanin and two flavonols from the blue flowers
      of Meconopsis were identified by NMR spectroscopy as being cyanidin 3-O-[(6-O
      malonyl-2-O-B-D-xylopyranosyl)-beta-D-glucopyranoside]-7-O-beta-D
      glucopyranoside, kaempferol 3-O-(6-O-beta-D-glucopyranosyl)-beta-D
      glucopyranoside and kaempferol 3-O-(6-O-beta-D-glucopyranosyl)-beta-D
      galactopyranoside respectively.

PMID- 11249105
TI  - Phenylbutanoids and stilbene derivatives of Rheum maximowiczii.
AB  - The methanol extract of the dried roots of Rheum maximowiczii afforded four
      phenylbutanoid and two stilbene derivatives. Their structures were established on
      the basis of chemical and spectroscopic studies.

PMID- 11249106
TI  - Canthin-6-one and beta-carboline alkaloids from Eurycoma harmandiana.
AB  - Two alkaloids, canthin-6-one 9-O-beta-glucopyranoside and 7-hydroxy-beta
      carboline 1-propionic acid, were isolated from the roots of Eurcoma harmandiana
      together with the five known canthin-6-one alkaloids, 9-hydroxycanthin-6-one, 9
      methoxycanthin-6-one, 9,10-dimethoxycanthin-6-one, canthin-6-one and canthin-6
      one N-oxide, and the two known beta-carboline alkaloids, beta-carboline 1
      propionic acid and 7-methoxy-beta-carboline 1-propionic acid. Their structures
      were based on analyses of spectroscopic data.

PMID- 11249107
TI  - The absolute configuration of (+)-isoshinanolone and in situ LC-CD analysis of
      its stereoisomers from crude extracts.
AB  - The absolute configuration of (+)-isoshinanolone, a wide-spread acetogenic
      metabolite from higher plants, has been determined by X-ray structure analysis of
      its new dibromide; accordingly, this natural tetralone is 3R,4R-configured, in
      agreement with previous degradative results. In addition, a first chiroptical on
      line stereoanalysis for isoshinanolones is presented, i.a. by HPLC on a chiral
      phase coupled to CD spectroscopy, giving pure CD spectra of all of the four
      stereoisomers of isoshinanolone directly from stereoisomeric mixtures.

PMID- 11249108
TI  - Saponins from the roots of Zygophyllum gaetulum and their effects on electrically
      stimulated guinea-pig ileum.
AB  - A new ursanolide, 3beta-O-alpha-L-rhamnopyranosyl-(1->2)-O-alpha-L
      arabinopyranosyl-(1->2)-beta-D-glucopyranosyl)oxy]-ursan-20beta,28-olide,
      zygophyloside N (1), and three known quinovic acid glycosides were isolated from
      the methanolic extract of the roots of Zygophyllum gaetulum. The crude extract,
      some fractions and 3-O-beta-D-glucopyranosyl quinovic acid 28-beta-D
      glucopyranosyl ester, significantly and dose-dependently, are able to reduce the
      electrically-induced contractions of isolated guinea-pig ileum. The structure of
      compound (1) was determined, using 1D and 2D NMR techniques.

PMID- 11249109
TI  - Five naphthalene glycosides from the roots of Rumex patientia.
AB  - Three novel and two known naphthalene glycosides were isolated from the roots of
      Rumex patientia L. (Polygonaceae). The structures of the new compounds were
      established, respectively as 2-acetyl-3-methyl-6-carboxy-1,8-dihydroxynaphthalene
      8-O-beta-D-glucopyranoside, 4,4"-binaphthalene-8,8"-O,O-di-beta-D-glucopyranoside
      and 2-acetyl-3-methyl-1,8-dihydroxynaphthalene-8-O-beta-D-glucopyranosyl (1-->3)
      beta-D-glucopyranoside on the basis of spectral analysis. The other napthalene
      glycosides were determined as nepodin-8-O-beta-D-glucopyranoside and torachrysone
      8-O-beta-D-glucopyranoside by comparison of their spectral data with those
      previously reported.

PMID- 11249110
TI  - The Pergamon Phytochemistry prize for creativity in Plant Biochemistry 2000 has
      been awarded to professor G.H. Neil Towers.

PMID- 11249111
TI  - The Phytochemical Society of Europe Research Award. 2000 PSE Research Award
      Lecturer.

PMID- 11249112
TI  - The conformational study of chitin and chitosan oligomers in solution.
AB  - The inter-residual dihedral angles phi and phip of chitin and chitosan oligomers
      were determined from experimental 3J(C-H) constants and ROESY cross peaks.

PMID- 11249113
TI  - Microwave assisted solid support synthesis of novel 1,2,4-triazolo[3,4-b]-1,3,4
      thiadiazepines as potent antimicrobial agents.
AB  - An environmentally benign and economic synthesis of 1,2,4-triazolo[3,4-b]-1,3,4
      thiadiazepines is described from readily accessible substituted 2-mercapto-1
      amino triazoles and substituted chalcones on basic alumina that are accelerated
      by exposure to microwaves. The reaction time has been brought down from hours to
      seconds with improved yield as compared to conventional heating. The method
      reported herein is devoid of the hazards of solution phase reactions. All the
      synthesised compounds were tested for their in vitro antibacterial and antifungal
      activity. Some compounds showed significant antimicrobial properties. The best
      activity was observed with compounds 3a, 3c, 4a and 4d.

PMID- 11249114
TI  - Synthesis and biological evaluation of 2-(3'-(1H-tetrazol-5-yl)
      bicyclo[1.1.1]pent-1-yl)glycine (S-TBPG), a novel mGlu1 receptor antagonist.
AB  - The design and synthesis of 2-(3'-(1H-tetrazol-5-yl)bicyclo[1.1.1]pent-1
      yl)glycine (S-TBPG), a novel mGluR1 antagonist is reported. S-TBPG is
      characterized by the bioisosteric replacement of the distal carboxy group of 2
      (3'-carboxybicyclo [1.1.1]pent-1-yl)glycine (S-CBPG) by a tetrazolyl moiety.
      Despite a moderate reduction in potency, S-TBPG is a selective mGluR1 antagonist
      (69 microM), with no activity at other mGluR subtypes. The interesting biological
      profile of S-TBPG, coupled with its peculiar chemical structure, is discussed in
      terms of the structure activity relationship (SAR) of mGluR1 antagonists.

PMID- 11249115
TI  - New bis-catechols 5-lipoxygenase inhibitors.
AB  - Three polyhydroxy-2-phenylnaphthalenes (1-3) and the oxy analogue of
      tetrahydroxypavinan (4) were prepared and evaluated for their antioxidant
      properties (inhibition of diphenylpycrylhydrazyl radical (DPPH), reduction of
      iron (III) ion) and inhibition of 5-lipoxygenase (5-LO) activity. Their three
      dimensional structures were established on the basis of spectroscopic data and
      semiempirical calculations. Compounds 1 and 2 were found as potent 5-LO
      inhibitors as nordihydroguaiaretic acid (NDGA), whereas 4 is 2.5 times less
      potent than NDGA. The reliability of the 3-D structures with the 5-LO inhibition
      properties is discussed. Their antioxidant properties show that tested compounds
      are expected to act as redox inhibitors.

PMID- 11249116
TI  - A new inhibitor design strategy for carboxypeptidase A as exemplified by N-(2
      chloroethyl)-N-methylphenylalanine.
AB  - N-(2-Chloroethyl)-N-methylphenylalanine was designed and synthesized in an
      optically active form as a novel class of mechanism-based inactivator for
      carboxypeptidase A (CPA). It was anticipated that the chloroethylamino moiety of
      the CPA bound inhibitor undergoes an intramolecular SN2 reaction to generate a
      chemically reactive species (an aziridinium ion) which is expectedly subjected to
      a nucleophilic attack by the carboxylate of Glu-270, leading to covalent
      modification of the carboxylate. The irreversible nature of the inhibition of CPA
      by the inhibitor was supported by the kinetic data: the enzyme lost its enzymic
      activity in a time-dependent manner in the presence of the inhibitor and the
      inactivated CPA failed to regain the activity upon dialysis. Interestingly, the
      (R)-isomer that belongs to the D-series was more potent than its enantiomer.

PMID- 11249117
TI  - Symmetrical cationic triglycerides: an efficient synthesis and application to
      gene transfer.
AB  - Some cationic triglycerides 1Aa-1Cb which have a symmetrical structure were
      effectively synthesized and formulated into cationic liposomes with the co-lipid
      dioleoylphosphatidylethanolamine (DOPE) and/or dilauroylphosphatidylcholine
      (DLPC). The plasmid encoding a luciferase was delivered into CHO cells by using
      these cationic liposomes. Our symmetrical cationic triglycerides showed high
      transfection activity when DOPE was used as a co-lipid. Among the symmetrical
      cationic triglycerides synthesized here, 1Ab and 1Ac, which have an oleoyl group
      at the 1- and 3-position in the glycerol backbone and also have a relatively long
      linker connecting the 2-hydroxy group in glycerol with the quaternary ammonium
      head group, were found to be the most suitable for gene delivery into cells. The
      transfection activity of the symmetrical cationic triglyceride 1Ab was comparable
      with that of its asymmetrical congener 6 and several times higher than that of
      Lipofectin.

PMID- 11249118
TI  - Design, syntheses, and structure-activity relationships of indan derivatives as
      endothelin antagonists; new lead generation of non-peptidic antagonist from
      peptidic leads.
AB  - A new lead generation of non-peptidic ET(A) antagonists from two peptidic ET(A)
      selective ones, BQ-123 and FR139317, was performed. Using computer assisted
      molecular modeling, a putative pharmacophore was constructed from the
      superposition of the reported three-dimensional structure of the cyclic peptide
      BQ-123 and a presumable beta-turn active conformation of the linear peptide
      FR139317 formed by an intramolecular hydrogen bond. According to this model, a
      new series of indan derivatives were designed and synthesized. Among these, 5
      isobutyrylamino-6-(1-naphthylmethyloxy)-3-(2-thienyl)-1-indancarboxylic acid (1b)
      showed a moderate ET(A) antagonistic activity (IC50 = 28 microM).

PMID- 11249119
TI  - Purification and characterisation of an ester hydrolase from a strain of
      Arthrobacter species: its application in asymmetrisation of 2-benzyl-1,3
      propanediol acylates.
AB  - An ester hydrolase (ABL) has been isolated from a strain of Arthrobacter species
      (RRLJ-1/95) maintained in the culture collection of this laboratory. The purified
      enzyme has a specific activity of 1700 U/mg protein and is found to be composed
      of a single subunit (Mr 32,000), exhibiting both lipase and esterase activities
      shown by hydrolysis of triglycerides and p-nitrophenyl acetate respectively.
      Potential application of the enzyme concerns the asymmetrisation of prochiral 2
      benzyl-1,3-propanediol esters besides enantioselective hydrolysis of alkyl esters
      of unsubstituted and substituted 1-phenyl ethanols.

PMID- 11249120
TI  - Effect of the complexation with cyclodextrins on the in vitro antiviral activity
      of ganciclovir against human cytomegalovirus.
AB  - The toxicity of the molecules currently used in the treatment of human
      cytomegalovirus (HCMV) in immunocompromised hosts often causes interruption of
      the therapy. Cyclodextrins (Cds), oligosaccharides possessing a hydrophobic
      cavity, have the property of forming inclusion complexes with a great number of
      molecules, improving their bioavailability and their biological properties. In
      this study, we have tested the ability of three native Cds to improve the
      antiviral effect of ganciclovir (GCV) on two HCMV strains: AD169, a reference
      susceptible strain, and RC11, a GCV resistant strain. The efficacy of the GCV,
      expressed in IC50 values, showed no improvement in the presence of alpha-Cd,
      while the use of beta- and gamma-Cd improved by 6- and 4-fold, respectively, its
      antiviral activity tested on AD169 strain. The influence of beta- or gamma-Cd on
      GCV efficiency evaluated on RC11 strain showed a decrease of the IC50. Parallel
      NMR studies were undertaken in order to characterize formation of [GCV:Cd]
      complexes. The results showed that complexation between alpha- or gamma-Cd and
      GCV did not occur. In contrast, spectra proved that beta-Cd formed an inclusion
      complex with GCV. This complex was characterized in UV-Visible spectrophotometry
      and the influence of the beta-Cd on the GCV penetration in cells was measured.
      The use of Cds as carriers of antiviral drugs would be a good alternative to
      traditional treatment, because it may allow the administration of lower doses and
      so continuous treatment by reducing the toxic effects of drugs.

PMID- 11249121
TI  - Searching for allosteric effects via QSARs.
AB  - A study of our database of 7,000 QSARs involving chemical-biological interaction
      uncovered 11 examples where the QSARs all contain inverted parabolas based on
      molecular refractivity. That is, biological activity first decreases with
      increase in MR and then increases. Two of the examples are for enzymes:
      cyclooxygenase and trypsin. The others are for various receptors. The results
      seem to be best rationalized by the larger compounds inducing a change in a
      receptor unit that allows for a new mode of interaction.

PMID- 11249122
TI  - 3-D QSAR studies of triazolinone based balanced AT1/AT2 receptor antagonists.
AB  - Essential structural and physicochemical requirements in terms of common
      biophoric sites (pharmacophore) and secondary sites for binding and interacting
      with AT1 and AT2 receptors have been identified using APEX-3-D expert system on
      16 N2- aryl triazolinone biphenyl sulphonamides. Among several biophoric 3-D QSAR
      models two models (Nos. 1 and 2) having R2 > 0.7, chance <0.05 and match >0.5 and
      two models (Nos. 3 and 4) having R2 > 0.89, chance <0.03 and match >0.5 with
      three biophoric sites and two secondary sites (except model No. 4 with three
      secondary sites) describe the variation in AT1 and AT2 antagonistic activities,
      respectively.

PMID- 11249124
TI  - Oxidation of oxa and thia fatty acids and related compounds catalysed by 5- and
      15-lipoxygenase.
AB  - The modified fatty acids, (Z,Z,Z)-(octadeca-6,9,12-trienyloxy)acetic acid,
      (Z,Z,Z)-(octadeca-9,12,15-trienyloxy)acetic acid, (all-Z)-(eicosa-5,8,11,14
      tetraenyloxy)acetic acid, (all-Z)-(eicosa-5,8,11,14-tetraenylthio)acetic acid, 3
      [(all-Z)-(eicosa-5,8,11,14-tetraenylthio)]propionic acid, (all-Z)-(eicosa
      5,8,11,14-tetraenylthio)succinic acid, N-[(all-Z)-(eicosa-5,8,11,14
      tetraenoyl)]glycine and N-[(all-Z)-(eicosa-5,8,11,14-tetraenoyl)]aspartic acid,
      all react with soybean 15-lipoxygenase. The products were treated with
      triphenylphosphine to give alcohols, which were isolated using HPLC. Analysis of
      the alcohols using negative ion tandem electrospray mass spectrometry, and by
      comparison with compounds obtained by autoxidation of arachidonic acid, shows
      that each enzyme-catalysed oxidation occurs at the omega-6 position of the
      substrate. In a similar fashion, it has been found that (Z,Z,Z)-(octadeca-6,9,12
      trienyloxy)acetic acid, (Z,Z,Z)-(octadeca-9,12,15-trienyloxy)acetic acid, (all-Z)
      (eicosa-5,8,11,14-tetraenylthio)acetic acid and 3-[(all-Z)-(eicosa-5,8,11,14
      tetraenylthio)]propionic acid each undergoes regioselective oxidation at the
      carboxyl end of the polyene moiety on treatment with potato 5-lipoxygenase.
      Neither (all-Z)-(eicosa-5,8,11,14-tetraenylthio)succinic acid nor N-[(all-Z)
      (eicosa-5,8,11,14-tetraenoyl)]aspartic acid reacts in the presence of this
      enzyme, while N-[(all-Z)-(eicosa-5,8,11,14-tetraenoyl)]glycine affords the C11'
      oxidation product. The alcohol derived from (Z,Z,Z)-(octadeca-6,9,12
      trienyloxy)acetic acid using the 15-lipoxygenase reacts at the C6' position with
      the 5-lipoxygenase.

PMID- 11249123
TI  - Non-peptidic inhibitors of human chymase. Synthesis, structure-activity
      relationships, and pharmacokinetic profiles of a series of 5-amino-6-oxo-1,6
      dihydropyrimidine-containing trifluoromethyl ketones.
AB  - Chymase possesses a wide variety of actions, including promotion of angiotensin
      II production and histamine release from mast cells. However, due to a lack of
      effective inhibitors featuring both high inhibitory activity and high metabolic
      stability, the pathophysiological role of chymase has not been fully elucidated.
      We designed non-peptidic inhibitors based on the predicted binding mode of the
      peptidic chymase inhibitor Val-Pro-Phe-CF3 and demonstrated that the Val-Pro unit
      is replaceable with a (5-amino-6-oxo-2-phenyl-1,6-dihydro-1-pyrimidinyl)acetyl
      moiety. Structure-activity relationship studies revealed that phenyl substitution
      at the 2-position of the pyrimidinone ring is indispensable for high activity.
      The most potent compound 1h (Ki = 0.0506 microM) is superior in potency to the
      parent peptidic inhibitor Val-Pro-Phe-CF3 and has good selectivity for chymase
      over other proteases. The related analogue 1e was orally absorbed and maintained
      high plasma levels for at least 2h. These results suggest that the derivatives
      reported here could be developed as agents for treatment of chymase-induced
      disease.

PMID- 11249125
TI  - Molecular modeling and QSAR analysis of the interaction of flavone derivatives
      with the benzodiazepine binding site of the GABA(A) receptor complex.
AB  - A large number of structurally different classes of ligands, many of them sharing
      the main characteristics of the benzodiazepine (BDZ) nucleus, are active in the
      modulation of anxiety, sedation, convulsion, myorelaxation, hypnotic and amnesic
      states in mammals. These compounds have high affinity for the benzodiazepine
      binding site (BDZ-bs) of the GABA(A) receptor complex. Since 1989 onwards our
      laboratories established that some natural flavonoids were ligands for the BDZ-bs
      which exhibit medium to high affinity in vitro and anxiolytic activity in vivo.
      Further research resulted in the production of synthetic flavonoid derivatives
      with increased biochemical and pharmacological activities. The currently accepted
      receptor/pharmacophore model of the BDZ-bs (Zhang, W.; Koeler, K. F.; Zhang, P.;
      Cook, J. M. Drug Des. Dev. 1995, 12, 193) accounts for the general requirements
      that should be met by this receptor for ligand recognition. In this paper we
      present a model pharmacophore which defines the characteristics for a ligand to
      be able to interact and bind to a flavone site, in the GABA(A) receptor. closely
      related to the BDZ-bs. A model of a flavone binding site has already been
      described (Dekermendjian, K.; Kahnberg, P.; Witt, M. R.; Sterner, O.; Nielsen,
      M.; Liljerfors, T. J. Med. Chem. 1999, 42, 4343). However, this alternative model
      is based only on graphic superposition techniques using as template a non-BDZ
      agonist. In this investigation all the natural and synthetic flavonoids found to
      be ligands for the BDZ-bs have been compared with the classical BDZ diazepam. A
      QSAR regression analysis of the parameters that describe the interaction
      demonstrates the relevance of the electronic effects for the ligand binding, and
      shows that they are associated with the negatively charged oxygen atom of the
      carbonyl group of the flavonoids and with the nature of the substituent in
      position 3'.

PMID- 11249126
TI  - Synthetic and biological activity evaluation studies on novel 1,3
      diarylpropenones.
AB  - Fourteen novel C-prenylated and O-allylated 1,3-diarylpropenones (chalcones) were
      synthesized by Claisen-Schmidt condensation reaction of C-prenylated/O-allylated
      acetophenones with appropriate aldehydes; twelve of these model chalcones were
      screened in an assay based on the confrontation of invasive human MCF-7/6 mammary
      carcinoma cells with fragments of normal embryonic chick heart in vitro. Out of
      the twelve chalcones tested, three were found to exhibit potent anti-invasive
      activity. Some of these chalcones and their precursor acetophenones were also
      tested for inhibition of initiation of lipid peroxidation in rat liver
      microsomes; a prenylated acetophenone carrying two methoxy groups and two free
      phenolic hydroxy functions was found to be a potential antioxidant.

PMID- 11249127
TI  - Synthesis of variously oxidized abietane diterpenes and their antibacterial
      activities against MRSA and VRE.
AB  - Variously oxidized 12 natural abietanes, 6,7-dehydroferruginol methyl ether (3),
      ferruginol (5), 11-hydroxy-12-oxo-7,9(11),13-abietatriene (7), royleanone (9),
      demethyl cryptojaponol (12), salvinolone (14), sugiol methyl ether (16), sugiol
      (17), 5,6-dehydrosugiol methyl ether (19), 5,6-dehydrosugiol (20), 6beta
      hydroxyferruginol (23), and taxodione (25) were synthesized. Antimicrobial
      activities of synthesized phenolic diterpenes and their related compounds against
      MRSA and VRE were evaluated. Phenols (12-hydroxyabieta-8,11,13-trien-6-one 22 and
      23), catechols (12 and 14) and taxodione 25 showed potent activity with 4-10
      microg/mL of MIC against MRSA and 4-16 microg/mL of MIC against VRE. (-)
      Ferruginol showed more potent activity than natural type (+)-ferruginol. Quinone
      methide 7 showed the most potent activity with 0.5-1 microg/mL of MIC against
      both MRSA and VRE.

PMID- 11249129
TI  - Synthesis of sulfoquinovosylacylglycerols, inhibitors of eukaryotic DNA
      polymerase alpha and beta.
AB  - Sulfoquinovosyldiacylglycerols (SQDGs) and sulfoquinovosylmonoacylglycerols
      (SQMGs), bearing diverse fatty acids, were synthesized from D-glucose, and were
      examined for enzymatic inhibitions of DNA polymerase alpha and beta. These
      results indicated that the carbon numbers of the fatty acids were highly related
      to the activities, at least in vitro, of eukaryotic DNA polymerase inhibition.

PMID- 11249130
TI  - Broad-spectrum antimicrobial activity of hemoglobin.
AB  - While hemoglobin is one of the most well characterized proteins due to its
      function in oxygen transport, few additional properties of hemoglobin have been
      described. While screening serum samples for novel antimicrobial factors, it was
      found that intact hemoglobin tetramers, including that from human, exhibited
      considerable activity against gram-positive and gram-negative bacteria, and
      fungi. To further characterize this surprising activity, the antimicrobial
      potency of sections of human hemoglobin was tested against a panel of
      microorganisms. In all cases separate testing of the alpha and beta subunits
      provided activity at least as potent as the intact tetramer. This activity is
      derived from the protein portion of hemoglobin since removal of the heme
      prosthetic group did not lead to decreases in potency. In addition, cyanogen
      bromide cleavage of both subunits provided fragments that still contained
      substantial antimicrobial activity. It has been possible to map specific regions
      of the human hemoglobin molecule that are responsible for significant
      antimicrobial activity. The carboxyl terminal thirty amino acids of the beta
      subunit, which form a cationic alpha-helix based on the crystal structure of the
      intact tetramer, were active against Escherichia coli, Staphylococcus aureus and
      Candida albicans. In view of the fact that different hemoglobin-derived peptide
      fragments exhibit diverse antibiotic activities, it is conceivable that, in
      addition to its role in oxygen transport. hemoglobin functions as an important
      multi-defense agent against a wide range of microorganisms.

PMID- 11249131
TI  - N-Acyl-1,2,3,4a,5,10b-hexahydro-[1]benzopyrano-[3,4-b][1,4]oxazine-9
      carbonitriles as bladder-selective potassium channel openers.
AB  - Optically active N-acyl-5,5-dimethyl-1,2,3,4a,5,10b-hexahydro-[1]benzopyrano[3,4
      b][1,4]oxazine-9-carbonitriles 2-22 were synthesized as rigid analogues of
      cromakalim. The (4aR, 10bR)-N-benzoyl derivative (-)-11 was identified as a
      bladder-selective KCO (IC50, bladder = 8.2 microM, C50, portal vein = 34.5
      microM). Among the analogues of 11 with substitution on the benzoyl moiety, the 3
      methyl analogue (-)-14 showed highly potent and selective activity at portal vein
      (IC50, bladder = 279 microM, IC50, portal vein = 0.54 microM). The 4-bromo
      analogue (-)-19 (IC50, bladder = 2.0 microM, IC50, portal vein = 8.1 microM) and
      the 4-hydroxy analogue (-)-21 (IC50, bladder = 3.8 microM, IC50, portal vein = 75
      microM) showed enhanced activity at the bladder, while maintaining unprecedented
      bladder selectivity in vitro. The N-benzenesulfonyl analogue (-)-22, a bioisoster
      of (-)-11, showed similar activity at the bladder with enhanced selectivity
      (IC50, bladder = 11.6 microM, IC50, portal vein = 120 microM).

PMID- 11249128
TI  - Rebeccamycin analogues from indolo[2,3-c]carbazole.
AB  - Glycosylated indolocarbazoles related to the antibiotic rebeccamycin represent an
      important series of antitumor drugs. In the course of structure-activity
      relationship studies, we report the synthesis of two new derivatives containing
      an indolo[2,3-c]carbazole chromophore instead of the conventional indolo[2,3
      a]carbazole unit found in the natural metabolites. The N-methylated compound 8
      containing one glucose residue behaves as a typical DNA intercalating agent, as
      judged from circular and electric linear dichroism measurements with purified
      DNA. In contrast, the bis-glycosylated derivative 7 containing a glucose residue
      on each indole nitrogen has lost its capacity to form stable complexes with DNA.
      DNA relaxation experiments reveal that the two drugs 7 and 8 have weak effects on
      human DNA topoisomerase I. The modified conformation of the indolocarbazole
      chromophore is detrimental to the stabilization of topoisomerase I-DNA complexes.
      The lack of potent topoisomerase I inhibition leads to decreased cytotoxicity
      but, however, we observed that the DNA-intercalating mono-glycosyl derivative 8
      is about 5 times more cytoxic than the bis-glycosyl analogue 7. The study
      suggests that the naturally-occurring indolo[2,3-a]carbazole skeleton should be
      preserved to maintain the topoisomerase I inhibitory and cytotoxic activities.

PMID- 11249132
TI  - Stereoselective inhibition of glutamate carboxypeptidase by chiral
      phosphonothioic acids.
AB  - A series of phosphonothioic acid derivatives of (S)-2-hydroxyglutarate with
      various alkyl or aryl ligands to the central phosphorus atom was examined for
      stereoselective inhibition of the glutamate carboxypeptidase, carboxypeptidase G.
      The inhibitory potencies of these stereoisomers were compared to corresponding
      synthetic phosphonic acid analogues in order to reveal the significance of the
      sulfur ligand of the phosphonothioic acid motif upon the inhibition of this
      metallopeptidase. The acquisition of the individual phosphonothioic acid
      diastereomers was achieved through the resolution of the respective phosphonate
      ester precursors. In all cases, the (+)p-diastereomers of these phosphonothioic
      acid derivatives of (S)-2-hydroxyglutarate were found to be more potent
      inhibitors of glutamate carboxypeptidase than the corresponding (-)p antipodes
      with the most dramatic difference observed for the butyl isomers (13.6-fold).
      Based upon Ki values obtained, the most potent inhibitor of the series by nearly
      an order of magnitude was the (+)p-n-butylphosphonothioic acid derivative,
      revealing specific structural and stereochemical requirements by this glutamate
      carboxypeptidase. With the exception of the (+)p-n-butyl analogue, the isosteric
      replacement of oxygen with sulfur of the phosphonic acid moiety did not enhance
      inhibitory potency.

PMID- 11249133
TI  - Synthesis and evaluation of A-ring diastereomers of 1alpha,25-dihydroxy-22
      oxavitamin D3 (OCT).
AB  - A-ring diastereomers of 1alpha,25-dihydroxy-22-oxavitamin D3 (OCT) (2), 3-epi
      1alpha,25-dihydroxy-22-oxavitamin D3 (3-epiOCT) (3) and 1,3-diepi-1alpha,25
      dihydroxy-22-oxavitamin D3 (1,3-diepiOCT) (4) were synthesized by the convergent
      method. In vitro binding affinity for rat vitamin D binding protein and calf
      thymus vitamin D receptor, differentiation-inducing activity on HL-60 cells, and
      transcriptional activity of 3-epiOCT (3) and 1,3-diepiOCT (4) were evaluated in
      comparison with OCT (2), 1-epi-1alpha,25-dihydroxy-22-oxavitamin D3 (1-epiOCT)
      (5) and 1alpha,25-dihydroxyvitamin D3 (1).

PMID- 11249135
TI  - High affinity central benzodiazepine receptor ligands. Part 2: quantitative
      structure-activity relationships and comparative molecular field analysis of
      pyrazolo[4,3-c]quinolin-3-ones.
AB  - A large series of 2-aryl(heteroaryl)-2,5-dihydropyrazolo[4,3-c]quinolin-3(3H)
      ones (PQ, 106 compounds), carrying appropriate substituents at the quinoline and
      N2-phenyl rings, were designed, prepared and tested as central benzodiazepine
      receptor ligands. Compounds with an affinity significantly higher than the parent
      compound CGS-8216 were obtained, the most active ligand showing a pIC50 = 10.35.
      Hansch and comparative molecular field analyses gave coherent results suggesting
      the main structural requirements of high receptor binding affinity. The possible
      formation of a three-centred hydrogen bond (HB) at the HB donor site H2, as a key
      interaction for high receptor binding affinity, was assessed by the calculation
      and comparison of the molecular electrostatic potentials of a series of selected
      ligands.

PMID- 11249134
TI  - Synthesis and biological evaluation of prodrug-type anti-HIV agents: ester
      conjugates of carboxylic acid-containing dipeptide HIV protease inhibitors and a
      reverse transcriptase inhibitor.
AB  - On the basis of substrate transition-state mimic concept of HIV protease, a
      series of small-sized dipeptide inhibitors containing hydrophilic carboxyl group
      were designed and synthesized. These dipeptide inhibitors showed good HIV
      protease inhibitory activity, but their anti-HIV activity was poor. The low
      antiviral activities of these inhibitors were probably due to their inadequate
      cell membrane permeability caused by the presence of a free carboxylic acid in
      the inhibitors. Based on the prodrug concept as well as the combination of two
      different classes of anti-HIV agents, conjugates of HIV protease inhibitors with
      a nucleoside reverse transcriptase inhibitor were synthesized. Some of these
      conjugates exhibited excellent antiviral activity compared with that of
      individual inhibitors. The synergistic enhancement of anti-HIV activities of
      these conjugates may be due to their ability to penetrate into the target cell
      and subsequent regeneration of two different classes of anti-HIV agents in the
      cytoplasm.

PMID- 11249136
TI  - Positioning of the carboxamide side chain in 11-oxo-11H-indeno[1,2
      b]quinolinecarboxamide anticancer agents: effects on cytotoxicity.
AB  - A series of 11-oxo-11H-indeno[1,2-b]quinolines bearing a carboxamide-linked
      cationic side chain at various positions on the chromophore was studied to
      determine structure-activity relationships between cytotoxicity and the position
      of the side chain. The compounds were prepared by Pfitzinger synthesis from an
      appropriate isatin and 1-indanone, followed by various oxidative steps, to
      generate the required carboxylic acids. The 4- and 6-carboxamides (with the side
      chain on a terminal ring, off the short axis of the chromophore) were effective
      cytotoxins. The dimeric 4- and 6-linked analogues were considerably more
      cytotoxic than the parent monomers, but had broadly similar activities. In
      contrast, analogues with side chains at the 8-position (on a terminal ring but
      off the long axis of the chromophore) or 10-position (off the short axis of the
      chromophore but in a central ring) were drastically less effective. The 4,10- and
      6,10-biscarboxamides had activities between those of the corresponding parent
      monocarboxamides. The first of these showed good activity against advanced
      subcutaneous colon 38 tumours in mice.

PMID- 11249137
TI  - New antimetastatic hypoxic cell radiosensitizers: design, synthesis, and
      biological activities of 2-nitroimidazole-acetamide, TX-1877, and its analogues.
AB  - We designed, based on the molecular orbital (MO) calculation, synthesized, and
      evaluated the biological activities of the new antimetastatic hypoxic cell
      radiosensitizer, 2-nitroimidazole-acetamide, TX-1877, and its analogues. Each
      analogue has an electron-affinic imidazole group, an acetamide group and a
      certain hydrophilic group to control its biological effect, toxicity, and
      pharmacokinetics. In in vitro radiosensitization assay, most TX-1877 analogues,
      which have an electron affinity (EA) of more than 0.9 eV and partition
      coefficient (P) of more than 0.021, showed satisfactory enhancement ratios (ER >
      1.60) at doses of I mM. On the other hand, imidazole analogues, such as TX-1908
      (EA = 0.67 eV), TX-1910 (EA = -0.34 eV) and TX-1931 (EA = -0.37 eV), which have
      low electron affinities, had an ER of 1.31 or less. TX-1877 and KIN-806
      effectively inhibited tumor regrowth when administered with irradiation in vivo
      at a dose of 0.4 mg/g. Tumor lung metastasis was inhibited by treatment with
      either TX-1877 or KIN-806 without irradiation at a dose of 0.4 mg/g. TX-1877
      reduced markedly the mean number of metastatic lung nodules in comparison with
      KIN-806. Moreover, TX-1877 and KIN-806 enhanced macrophage and helper T
      lymphocyte infiltration for 3 weeks after drug treatment. TX-1877 shows a high EA
      value and has the C2 of HOMO localizing on N-methylamide and the C2 of LUMO
      localizing on 2-nitroimidazole group. The MO data might be useful for designing a
      bifunctional hypoxic cell radiosensitizer. TX-1877 and its analogues are
      potential antimetastatic hypoxic cell radiosensitizers, which would improve the
      efficiency of radiotherapy and quality of life in cancer treatment.

PMID- 11249138
TI  - Orally active cephalosporins. Part 3: synthesis, structure-activity relationships
      and oral absorption of novel C-3 heteroarylmethylthio cephalosporins.
AB  - A series of 7beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3
      (heteroarytmethylthio)cephalosporins was designed, synthesized and evaluated for
      antibacterial activity and oral absorption in rats. Antibacterial activity was
      markedly influenced by the structure of the heteroaromatic ring moiety. Oral
      absorption was influenced by the heteroaromatic ring moiety as well as by the
      arrangement of heteroatoms. Among these compounds, FK041 (2o), having a 4
      pyrazolylmethylthio moiety, showed potent antibacterial activity against both
      gram-positive and gram-negative bacteria including Haemophilus influenzae.
      Further, it showed higher oral absorption than CFDN.

PMID- 11249139
TI  - Synthesis and anti-HIV activity of nonatyrosine N- and O1-9-decasulfate.
AB  - To develop a potent and effective anti-HIV compound with a definite polyanionic
      structure, synthesis of oligotyrosine sulfates by oligomerization with
      simultaneous sulfation of tyrosine was tried. One component was successfully
      isolated from the mixture containing many products as its sodium salt (Y-ART-4)
      and was identified as the salt of nonatyrosine N- and O1-9-decasulfate, NaO3S
      [Tyr(SO3Na)]9-ONa. Anti-HIV activity of Y-ART-4, determined from the protection
      it provided against HIV-induced cytopathic effects, was almost the same with that
      of dextran sulfate and curdlan sulfate.

PMID- 11249140
TI  - Synthesis and chain length-anti-HIV activity relationship of fully N- and O
      sulfated homooligomers of tyrosine.
AB  - Fully N- and O-sulfated homooligomers from octamer to nonadecamer of tyrosine
      were obtained as their sodium salts, aO3S-[Tyr(SO3Na)]n-ONa (n = 8-19), from
      reaction mixtures of tyrosine with sulfur trioxide trimethylamine and pyridine
      comlexes, respectively, in pyridine. Their anti-HIV activity increased along with
      the increase of the chain length up to the dodecamer, maintained the same level
      to the length of the heptadecamer and then decreased. The maximal activity level
      was the same as or higher than that of dextran and curdlan sulfates.

PMID- 11249141
TI  - Syntheses and hydrolysis of basic and dibasic ampicillin esters tailored for
      intracellular accumulation.
AB  - Readily hydrolysable basic and dibasic esters of ampicillin were synthesised by
      alkylation of the carboxylate function of ampicillin to obtain prodrugs that may
      accumulate in cells and allow for an intracellular delivery of ampicillian (Fan
      et al., Bioorg. Med. Chem. Lett. 1997, 7, 3107). We found that the beta-lactam
      ring cleavage and the hydrolysis of the ester function were competitive
      reactions. The prerequisite for biological activity of compounds of this type is
      therefore that ester hydrolysis proceeds faster than ring opening. Some
      synthesised compounds show promise as prodrugs since they displayed a reasonable
      stability and regenerate large quantities of bioactive ampicillin in broth.

PMID- 11249142
TI  - Cysteinyl peptide inhibitors of Bacillus cereus zinc beta-lactamase.
AB  - Several cysteinyl peptides have been synthesised and shown to be reversible
      competitive inhibitors of the Bacillus cereus metallo-beta-lactamase. The pH
      dependence of pKi indicates that the thiol anion displaces hydroxide ion from the
      active site zinc(II). D,D-Peptides bind to the enzyme better than other
      diastereoisomers, which is compatible with the predicted stereochemistry of the
      active site.

PMID- 11249143
TI  - Design, synthesis and preliminary biological evaluation of a focused
      combinatorial library of stereodiverse carbohydrate-scaffold-based
      peptidomimetics.
AB  - A focused combinatorial library of 126 mimetics of the RGD sequence based on
      sugar scaffolds have been rationally constructed using molecular modeling, with a
      particular emphasis on the stereodiversity of the library. A liquid phase, mix
      and divide synthesis was used, active compounds being identified by using
      orthogonal libraries and recursive deconvolution strategies.

PMID- 11249144
TI  - Highly potent cell differentiation-inducing analogues of 1alpha,25
      dihydroxyvitamin D3: synthesis and biological activity of 2-methyl-1,25
      dihydroxyvitamin D3 with side-chain modifications.
AB  - Eight 2-methyl substituted analogues of 20-epi-22R-methyl-1alpha,25
      dihydroxyvitamin D3 (5) and 20-epi-24,26,27-trihomo-22-oxa-1alpha,25
      dihydroxyvitamin D3 (6: KH-1060) were convergently synthesized. Preparation of
      the CD-ring portions with modified side chains of 5 and 6, followed by palladium
      catalyzed cross-coupling with the A-ring enyne synthons (20a-d), (3S,4S,5R)-,
      (3S,4R,5R)-, (3S,4S,5S)- and (3R,4R,5S)-3,5-bis[(tert-butyldimethylsilyl)oxy]-4
      methyloct-1-en-7-yne, afforded two sets of four A-ring stereoisomers of 20-epi
      2,22-dimethyl-1,25-dihydroxyvitamin D3 (7a-d) and 20-epi-24,26,27-trihomo-2
      methyl-22-oxa-1,25-dihydroxyvitamin D3 (8a-d). The biological profiles of the
      hybrid analogues were assessed in terms of affinity for vitamin D receptor (VDR)
      and HL-60 cell differentiation-inducing activity in comparison with the natural
      hormone. The combined modifications of the A-ring at the 2-position and the side
      chain yielded analogues with high potency.

PMID- 11249145
TI  - The discovery of RPR 200765A, a p38 MAP kinase inhibitor displaying a good oral
      anti-arthritic efficacy.
AB  - RPR132331, a 2-(2-dioxanyl)imidazole, was identified as an inhibitor of tumour
      necrosis factor (TNF)alpha release from lipopolysaccharide (LPS)-stimulated human
      monocytes. An intensive programme of work exploring the biology, toxicity and
      physical chemistry of a novel series of inhibitors, derived from RPR132331, has
      led to the identification of RPR200765A, a development candidate for the
      treatment of rheumatoid arthritis (RA). RPR200765A is a potent and selective
      inhibitor of p38 MAP kinase (IC50 = 50 nM). It inhibits LPS-stimulated TNFalpha
      release both in vitro, from human monocytes (EC50 = 110 nM), and in vivo in
      Balb/c mice (ED50 = 6 mg/kg). At oral doses between 10 and 30 mg/kg/day it
      reduces the incidence and progression in the rat streptococcal cell wall (SCW)
      arthritis model when administered in either prophylactic or therapeutic dosing
      regimens. The compound, which is a mesylate salt and exists as a stable
      monohydrate, shows good oral bioavailabiltiy (F = 50% in the rat) and excellent
      chemical stability. The data from the SCW disease model suggests that RPR200765A
      could exhibit a profile of disease modifying activity in rheumatoid arthritis
      (RA) patients which is not observed with current drug therapies.

PMID- 11249146
TI  - Long-term follow-up of obstructive sleep apnea syndrome following surgery in
      children and adults.
AB  - Obstructive sleep apnea syndrome (OSAS) is characterized by recurrent apneas
      during sleep, resulting in repetitive hypoxemia. The present study
      retrospectively analyzed subjective and objective assessments of the patients
      with OSAS in a relatively long-term follow-up. From February 1986 to August 1996,
      53 patients received surgical treatment for OSAS and snoring. Thirty-seven (27
      males and 10 females) out of 53 patients completed the questionnaire and
      postoperative sleep study was obtained in 6 patients. In 20 children (<15 years),
      snoring, sleep apnea, and daytime sleepiness completely disappeared in 12, 19,
      and 16, and improved in 8, 1, and 4, respectively. These findings confirm that
      tonsillectomy and/or adenoidectomy in children may be the first selection for
      treatment. In 17 adults, snoring, sleep apnea, and daytime sleepiness completely
      disappeared in 2, 5, and 8, improved in 11, 8, and 7, and was unchanged in 4, 4,
      and 1, respectively. The apnea index in adults was significantly decreased in
      both early and late postoperative periods. These results suggest that surgery is
      a satisfactory alternative for adult patients if performed accurate preoperative
      diagnosis of the localization of the airway collapse and careful long-term follow
      up.

PMID- 11249147
TI  - Immunoliposome-mediated gene transfer into cultured myotubes.
AB  - We encapsulated marker genes, pRSV-lacZ or pRSV-luc, in immunoliposomes
      conjugated with antibody targeting laminin B2 in the basal lamina of myotubes.
      The immunoliposomes were incubated with matured non-proliferating myotubes
      differentiated from C2C12 myoblasts. We then evaluated the efficiency of gene
      transfection by measuring luciferase activity and beta-galactosidase staining.
      The immunoliposomes conjugated with the antibody specific for myotubes were three
      times as efficient as control immunoliposomes conjugeted with an antibody not
      specific for myotubes. However, the efficiency was no more than that by the
      cationic liposomes without the antibody. These results suggest that laminin B2 is
      not effective in enhancing the efficiency of gene transfection for non
      proliferating myotubes. A specific antibody for surface antigen other than
      laminin B2 should be chosen in further studies.

PMID- 11249148
TI  - Selectivity and potency of agonists for the three subtypes of cloned human beta
      adrenoceptors expressed in Chinese hamster ovary cells.
AB  - The selectivities, potencies and efficacies of beta3-adrenoceptor (beta3-AR)
      agonists on human three beta-AR subtypes expressed in Chinese hamster ovary (CHO)
      cells were investigated using radioligand binding assay and cyclic AMP (cAMP)
      accumulation assay. The three beta-AR subtypes showed the nature of G protein
      coupled receptors with the constitutive activity. BRL37344, CL-316,243 and a
      newly synthesized beta3-AR agonist N-5984, 6-[2-(R)-[[2-(R)-(3-chlorophenyl)-2
      hydroxyethyl]amino]propyl]-2,3-dihydro-1,4-benzodioxine-2-(R)-carboxylic acid,
      were compared for the potency and selectivity for the beta3-AR. In the
      radioligand binding assay, the affinity of N-5984 for beta3-ARs was 14, 70 and
      220 times more potent than those of BRL37344, isoproterenol and CL-316,243,
      respectively. N-5984 had higher selectivity than BRL37344 for human beta3-ARs
      compared with either for beta1-ARs or beta2-ARs. N-5984 showed higher potency and
      intrinsic activity of cAMP production than BRL37344 in CHO cells expressing the
      beta3-ARs. CL-316,243 had almost no activity of cAMP production in CHO cells
      expressing any subtype of beta-ARs. These results indicate that N-5984 is the
      most potent and selective agonist for human beta3-ARs than any other agonists
      tested.

PMID- 11249149
TI  - Effects of methylmercury and inorganic mercury on the growth of nerve fibers in
      cultured chick dorsal root ganglia.
AB  - Inhibition of the growth of nerve fibers by mercurials was quantitatively
      estimated by measuring the length of fibers in the cultured chick dorsal root
      ganglion. Morphological changes in nonneuronal cells were also evaluated. The
      growth rates of nerve fibers were constant for 2 to 6 days after the start of
      incubation. Methylmercury depressed nerve fiber growth dose- and time-dependently
      by 50% and completely at 3 x 10(-6) M and 7 x 10(-6) M, respectively. About 10
      fold higher concentrations of inorganic mercury were required for the same extent
      of inhibition. The nerve fibers exposed to inorganic mercury shrank at an early
      stage of exposure and thereafter grew again within 24 hours. Electron microscopic
      examination revealed that methylmercury decreased microtubule mass extensively in
      nerve fibers, while inorganic mercury markedly altered surface membrane
      structure. These results suggested that microtubule disruption is involved in
      methylmercury-induced depression of nerve fibers but not in that induced by
      inorganic mercury. Characteristic effects on the growth of nerve fibers and the
      proliferation of nonneuronal cells were observed on the treatment with other
      metals such as cadmium, silver and chromium. Thus, dorsal root ganglion culture
      seems to be useful for the evaluation of toxic effects of metals in vitro.

PMID- 11249150
TI  - Short-term effects of prednisolone on neuromuscular transmission in the isolated
      mdx mouse diaphragm.
AB  - To determine the mechanism of the beneficial effects of prednisolone on Duchenne
      muscular dystrophy (DMD), we examined the short-term effects of prednisolone on
      neuromuscular transmission by using conventional microelectrode methods in the
      mdx mice. High (56 micromol/liter) and low (2.8 micromol/liter) concentrations of
      prednisolone were applied to a bath containing phrenic nerve-diaphragm
      preparations from mdx mice, and several parameters related to neuromuscular
      transmission were recorded. The high dose of prednisolone significantly decreased
      parameter n on quantal release by nerve impulse and decay time-constant of end
      plate potentials, which showed adverse effect on neuromuscular transmission. The
      low dose of prednisolone did not significantly increase quantal content, but
      could assist the compensatory reaction to maintain the safety margin of
      neuromuscular transmission in the mdx mice. Our results suggest that the latter
      effect represents one of the possible mechanisms of the therapeutic effects of
      prednisolone on DMD.

PMID- 11249151
TI  - Evaluation of salivary sialic acid level and Cu-Zn superoxide dismutase activity
      in type 1 diabetes mellitus.
AB  - In this study, our aim was to determine whether or not type 1 diabetes mellitus
      affects salivary sialic acid level and SOD activity. For this purpose,
      unstimulated saliva specimen was collected. Saliva sialic acid level and SOD
      activity were measured by the methods of Warren and Sun, respectively. We found
      significantly decline in salivary sialic acid level and SOD activity. The
      decrease of salivary sialic acid level in type 1 diabetes may be due to changes
      in the activities of the enzymes taking part of in the synthesis and catabolism
      of sialic acid. The main reason for the decrease of salivary SOD activity may be
      increased glycation of the enzyme and/or deleterious effect of increased free
      oxygen radicals by glycated proteins on SOD activity in diabetes. We conclude the
      decline both in sialic acid and SOD in saliva may be a possible factor leading to
      oral complications of diabetes mellitus.

PMID- 11249152
TI  - A cross-sectional study on the relationship between leisure or recreational
      physical activity and coronary risk factors.
AB  - Several researchers have investigated the relationship between physical activity
      and coronary risk factors. Little is known about the strength of the relationship
      between physical activity and each coronary risk factor. The aim of this study is
      to determined the strength of the relationship between leisure or recreational
      physical activity and selected coronary risk factors. The subjects were 781 male
      Japanese office workers who underwent an annual physical examination in 1999,
      including interview about the type and frequency of their leisure or recreational
      physical activities, other lifestyle questionnaire, and biological measurement,
      calculated a physical activity index (PAI) for each subject. To investigate the
      strength of the relationship between PAI and each coronary risk factor, we
      carried out multiple regression analysis. Smoking habit, log triglycerides, self
      rating depression scale (SDS) score, alcohol habit and left ventricular
      hypertrophy were significantly related to the physical activity (partial R2:
      0.031, 0.018, 0.016, 0.0092, 0.0075, respectively). Smoking habit was the
      strongest determinant of the physical activity. Furthermore, we found the inverse
      relationship between SDS score and physical activity independently.

PMID- 11249153
TI  - Decompressive surgery for typical lumbar spinal stenosis.
AB  - Between 1991 and 1992, 103 consecutive patients (average age, 65 years) underwent
      decompressive surgery for treatment of typical lumbar spinal stenosis. Clinical
      results at 1-year followup revealed that four patients had revision surgery. At 2
      to 5-years followup, there were no additional revision surgeries. Two patients
      underwent revision surgery for a deep infection, and two underwent revision
      surgery for a superficial infection. Outcome results showed that 77 patients
      completed the questionnaire, 15 were lost to followup and 11 died. Postoperative
      results showed that 64 of 77 patients had no or mild pain, 72 of 77 patients
      stated that they were satisfied or somewhat satisfied with their overall results
      of surgery, and 73 of 77 were satisfied with pain relief. Younger patients had
      greater improvement in function and a greater reduction in severity scores.
      However, satisfaction was similar in both groups. Survivorship results (failure
      was revision surgery) showed at the end of 4 years, a patient had a 95% chance of
      not having revision surgery. Statistically, there was no association between
      outcome and cofactors such as scoliosis, spondylolisthesis, number of levels
      decompressed, discectomy, or smoking. Satisfaction rates for older patients were
      similar to patients younger than 65 years although physical function scores and
      severity scores were less.

PMID- 11249154
TI  - A review of comorbidities and spinal surgery.
AB  - As the population ages, greater numbers of elderly patients will be considered
      for spinal surgery for spinal stenosis and complex primary and revision
      reconstructions. The age-related medical comorbidities impact not only on the
      decision to undertake a procedure but also impact the magnitude of the procedure.
      The surgeon must understand aging and medical comorbidities to facilitate
      preoperative decision-making and postoperative care. A review of the more common
      age-related pathophysiologic changes to the cardiovascular, pulmonary, and
      central nervous systems is undertaken. General recommendations for perioperative
      treatment are made relative to published series regarding the impact of age and
      medical comorbidities on short- and long-term outcomes.

PMID- 11249155
TI  - Cardiac risk stratification of patients with symptomatic spinal stenosis.
AB  - The leading cause of death in the perioperative period after noncardiac surgery
      is a cardiac event. As the number of lumbar surgeries performed in patients older
      than 65 years of age continues to increase, this patient population with
      neurogenic claudications is an at risk group for a cardiac event because of their
      age and associated cardiac risk factors. The authors attempted to document by
      means of cardiac chemical stress testing, the prevalence of silent ischemic
      cardiac disease in patients with neurogenic claudication who were candidates for
      elective lumbar surgery. Eleven of 140 patients (8%) had induced cardiac wall
      abnormalities on stress testing, indicating myocardial ischemia. The only risk
      factors associated with cardiac ischemia were smoking and history of heart
      disease. It is recommended that dobutamine stress echocardiography be performed
      in patients undergoing elective spinal surgery for symptomatic spinal stenosis if
      they have a history of previous heart disease, smoking, or both.

PMID- 11249156
TI  - Predicting complications in elderly patients undergoing lumbar decompression.
AB  - A retrospective chart review of 68 patients 70 years of age or older who
      underwent decompressive procedures of the lumbar spine with or without fusion for
      benign conditions was performed to determine the ability of preoperative
      assessment of medical comorbidities to predict early postoperative complications.
      Patients 70 years of age or older who underwent decompressive procedures on the
      lumbar spine with or without fusion from January 1, 1990 to June 30, 1996 were
      identified. A chart review focused on preoperative comorbid diseases and early
      postoperative complications. A telephone survey was performed to assess patient
      satisfaction. Thirty-four women and 34 men with an average of 76.5 years averaged
      1.6 comorbidities. Thirteen patients did not have comorbidities. The weighted
      comorbidity index resulted in an average score of 1.9. Eighty-five percent of the
      patients underwent posterolateral fusion. The total complication rate was 40%.
      Serious complications potentially affecting quality of life occurred in 12% of
      patients. The early mortality rate was 1.4%. The authors were unable to show a
      significant relationship between comorbidities and postoperative complications.
      Seventy-one percent of the 44 patients who were contacted at an average 42 months
      postoperatively were satisfied with their outcome. Elderly patients can safely
      undergo lumbar spinal procedures with an outcome similar to younger patients.

PMID- 11249157
TI  - Lumbar spinal stenosis assessment with computed tomography, magnetic resonance
      imaging, and myelography.
AB  - Degenerative spinal stenosis of the lumbar spine is caused by many factors, some
      of which include: disc herniation, ligamentum flavum and facet hypertrophy,
      spondylolisthesis, and compression fracture. Most often the stenosis is caused by
      a combination of these factors. The imaging modalities in routine use to evaluate
      these conditions are computed tomography, magnetic resonance imaging and computed
      tomography-myelogram. They each have their advantages and disadvantages although
      any one of these modalities can adequately diagnose lumbar stenosis. The overall
      accuracy rate of computed tomography, magnetic resonance imaging, and computed
      tomography-myelogram has been reported to be similar and even complimentary. It
      is recommended that the least invasive modality be performed first. Magnetic
      resonance imaging should be the first choice because it does not require ionizing
      radiation or contrast injection. The aim of the current study is to present the
      common causes of lumbar stenosis. Where appropriate, each case is shown with
      images from each modality so that their similarities and differences can be
      highlighted.

PMID- 11249158
TI  - Lumbar stenosis: a clinical review.
AB  - A brief history, classification, clinical presentation, and pertinent anatomy of
      spinal stenosis is presented. A thorough understanding of the etiology,
      pathologic features, and the correlation between symptoms and precisely where the
      thecal sac and nerve root impingement occurs is essential to interpret imaging
      studies and plan appropriate treatment.

PMID- 11249159
TI  - Therapeutic exercise in the treatment of patients with lumbar spinal stenosis.
AB  - Lumbar spinal stenosis is a condition that may cause significant pain and
      associated disability, especially in older patients. It is being recognized with
      increasing frequency as the population continues to age, and is the most common
      diagnosis associated with lumbar spine surgery in patients older than 65 years of
      age. The natural history of lumbar spinal stenosis is not necessarily one of
      progressive deterioration. Conservative treatment is advocated in patients with
      mild to moderate symptoms of lumbar spinal stenosis, and may include therapeutic
      exercise. The therapeutic exercise program must be prescribed with a thorough
      understanding of the contributing pathoanatomic and pathophysiologic factors, and
      should be tailored to each patient based on his or her history and physical
      examination. Components of the program are described in detail and include
      specific stretching and strengthening exercises, general conditioning exercises,
      and education in proper posture and body mechanics. Randomized controlled studies
      are needed to help clarify the indications for conservative versus surgical
      treatment, to determine which components of the therapeutic exercise program are
      the most beneficial, and to compare outcomes after conservative or surgical
      measures.

PMID- 11249160
TI  - Nonoperative treatment for lumbar spinal stenosis.
AB  - The natural history of degenerative lumbar spinal stenosis is documented poorly.
      Little is known about the efficacy of nonoperative treatments. An aggressive
      nonoperative treatment consisting of therapeutic exercise, analgesics, and
      epidural steroid injections is proposed. The clinical evaluation of the patients
      is reviewed and the relevance to the selection of the nonoperative treatment
      plans is emphasized. Efficacy of nonoperative treatment may depend greatly on the
      nature and severity of the patient's symptomatic and radiographic presentation.
      Several studies on nonoperative treatment of patients with between 1 and 5 years
      of followup suggest that variably 15% to 43% of patients will have continued
      improvement after nonoperative treatment.

PMID- 11249161
TI  - Release of flexors and intrinsic muscles for finger spasticity in cerebral palsy.
AB  - Between April 1987 and March 1996, 32 deformed hands of 31 patients with cerebral
      palsy were treated with combined release of the flexor digitorum profundus,
      flexor digitorum superficialis, and intrinsic muscles. Of these 31 patients, 26
      patients (27 hands) were followed up after treatment. Improvements were evaluated
      by the modified classification of Zancolli et al, the classification of House et
      al, the object handling score, and the activity of daily living score.
      Improvements of more than one level on an average were observed in the modified
      classification of Zancolli et al and the classification of House et al. The
      ability to grasp, pinch, and release increased with improvement of 2.5 points in
      the object handling score, and activities of daily living were enhanced with
      improvement of 2.4 points. The fine motor skills could be facilitated, and
      dexterity was restored in most patients.

PMID- 11249162
TI  - A prospective study of early tactile stimulation after digital nerve repair.
AB  - Forty-nine patients with 65 digital nerve injuries were randomized into two
      groups after nerve repair. Group 1 received early tactile stimulation and Group 2
      was a control group. The patients were assessed prospectively for 6 months for
      recovery of functional sensibility. Tactile stimulation in Group 1 was provided
      from 3 weeks after nerve repair with a specially designed rotating tactile
      stimulator and a pocket tactile stimulator. Constant two-point discrimination,
      moving two-point discrimination, and cutaneous pressure threshold were measured
      and sensibility was graded with the Medical Research Council (UK) sensibility
      grading. At 6 months, 68.8% of patients in Group 1 had a Medical Research Council
      grading of S3+ or S4 sensibility compared with 36 % in Group 2. With this
      prospective randomized study, the value of sensory reeducation in improving
      sensibility after digital nerve injury was confirmed. Starting tactile
      stimulation from the early postoperative period is recommended; however, use of
      the rotating tactile stimulator and pocket tactile stimulation need additional
      study.

PMID- 11249163
TI  - Combined intertrochanteric valgus and rotational acetabular osteotomy.
AB  - Results are reported for combined intertrochanteric valgus and rotational
      acetabular osteotomies in 18 dysplastic hips (17 patients), involving two types
      of femoral head and neck deformities, after an average followup of 13 years
      (range, 8.9-22.6 years). The mean age of the patients at the time of surgery was
      25 years (range, 11-36 years). Pain was the indication for surgery in all
      patients. The preoperative deformities were classified into two groups. Hips in
      Group I had an angular head and a normal or valgus neck. Hips in Group II had an
      ovoid head, a short neck in varus angulation, and relative overgrowth of the
      greater trochanter. There were seven hips (seven patients) in Group I, and 11
      hips (10 patients) in Group II. The sum of the most recent pain score and gait
      score of Merle d'Aubigne (a full score of 12 points) was 11 to 12 points for
      seven of 11 hips of Group II, and 11 to 12 points for only one of the seven hips
      of Group I. For patients with hip pain in Group II, this operation fairly
      consistently relieves pain for at least an average of 13 years, but whether the
      rate of development of osteoarthrosis is retarded is not known.

PMID- 11249164
TI  - Decompression, fusion, and instrumentation surgery for complex lumbar spinal
      stenosis.
AB  - Between 1990 and 1993, 54 consecutive patients were treated with decompression,
      fusion and instrumentation surgery for complex lumbar spinal stenosis. The mean
      age of the patients was 60 years. The average followup was 39 months. Clinically,
      there was one deep wound infection, and three mechanical failures. There were two
      staged operations. There were three revision surgeries performed for mechanical
      reasons. Of the 47 patients who completed the questionnaire, 96% of patients were
      very satisfied or somewhat satisfied with the operation, 98% were satisfied with
      relief of pain, 94% were satisfied with their ability to walk, 89% were satisfied
      with their strength, and 94% were satisfied with balance. Survivorship analysis
      (failure endpoint was revision surgery) revealed that at the end of 4 years, the
      patient had a 92% chance of not undergoing revision surgery for any reason
      (mechanical and infectious), and a 94% chance of not undergoing revision surgery
      for mechanical reasons. Lumbar decompression, fusion, and instrumentation surgery
      seems to be efficacious in patients with complex lumbar spinal stenosis
      (associated previous lumbar spine operations with evidence of radiographic
      instability, radiographic evidence of junctional stenosis after surgery,
      radiographic evidence of instability, degenerative spondylolisthesis greater than
      Grade I with instability, if present, and degenerative scoliosis with a curve
      greater than 20 degrees).

PMID- 11249165
TI  - Is the Harris hip score system useful to study the outcome of total hip
      replacement?
AB  - Although the Harris hip score frequently is used to assess the outcome of total
      hip replacement, only a few minor validity tests have been presented. The aim of
      this study was to perform a validity test of the Harris hip score and to test its
      reliability. Two cohorts were studied. First, 58 patients who had undergone total
      hip replacement 2 to 10 years earlier were evaluated by an orthopaedic surgeon
      and an experienced physiotherapist using the Harris hip score. The patients also
      answered the Western Ontario and McMaster University Osteoarthritis Index and the
      Medical Outcomes Study 36-Item Short-Form Health Survey. Second, 1,056 patients
      answered the Western Ontario and McMaster University Osteoarthritis Index and the
      Medical Outcomes Study 36-Item Short-Form Health Survey questionnaires. The
      results were compared with those of a subcohort of 344 patients who were
      evaluated using the Harris hip score. The following items were tested: content
      validity, convergent and divergent construct validity, criterion validity, test
      and retest reliability, internal consistency reliability, and interobserver
      reliability. The Medical Outcomes Study 36-Item Short-Form Health Survey, Western
      Ontario and McMaster University Osteoarthritis Index, and the Harris hip score
      showed high validity and reliability. The Harris hip score can be used by a
      physician or a physiotherapist to study the clinical outcome of hip replacement.

PMID- 11249166
TI  - Slipped capital femoral epiphysis: a prospective study of dynamic screw fixation.
AB  - Twenty-five consecutive children (29 hips) who had slipped capital femoral
      epiphysis of a mild degree (slip angle less than 30 degrees) were treated with
      dynamic screw fixation. The goal of dynamic screw fixation is to achieve physeal
      stability to prevent additional slippage and to avoid premature physeal closure.
      Seventeen boys and eight girls were followed up for an average of 7 years (range,
      4-13 years). There were 25 chronic slips, three acute slips, and one preslip. The
      average age at the time of surgery was 11.7 years for the girls (range, 11.1-12.9
      years) and 13.9 years for the boys (range, 9.4-16.1 years). The average time to
      physeal closure was almost the same in both genders (boys, 3.0 years; girls, 3.2
      years), ranging from 1.1 years to 6.3 years. No increase in the degree of
      slippage occurred; there were no perioperative complications, and avascular
      necrosis and chondrolysis were not apparent. In all 29 hips, no growth
      disturbance, including greater trochanteric overgrowth, coxa brevis, or coxa
      vara, was seen. According to the clinical criteria of Heyman and Herndon, 26 hips
      were rated either excellent or good, and two were rated fair. One was rated poor
      because of the presence of slight pain after strenuous exercise. The technique of
      dynamic screw fixation provides sufficient immediate and long-term fixation, does
      not promote premature physeal closure, and permits normal hip development.

PMID- 11249167
TI  - Knee reconstruction with prosthesis and muscle flap after total arthrectomy.
AB  - A massive prosthesis and medial gastrocnemius muscle transfer were used to
      reconstruct the knee after extracapsular en bloc excision for bone sarcoma.
      Magnetic resonance images showed intraarticular involvement. This technique was
      used in nine patients, six men and three women aged 18 to 51 years, with primary
      malignant bone tumors of the knee. Extraarticular resection of the knee,
      including the patella, was done in every case. A knee prosthesis was implanted,
      and the extensor mechanism was reconstructed by transfer of the medial
      gastrocnemius muscle and pes anserinus tendons. All resections had negative
      margins. There were no local recurrences, but metastases occurred in two
      patients. Infection was the only major complication and was seen in two patients.
      The mean postoperative Musculoskeletal Tumor Society score was 61% (range, 36%
      100%). The mean postoperative range of flexion was 62 degrees (range, 30 degrees
      90 degrees), and the mean extensor lag was 12 degrees (range, 0 degrees-40
      degrees). Three patients required a crutch to walk. The functional outcome was
      poor in the two patients whose proximal tibia was removed with the joint,
      suggesting that arthrodesis may be best in this situation. In properly selected
      patients, prosthesis and muscle flap reconstruction provides acceptable function
      and a good cosmetic result.

PMID- 11249168
TI  - Intraosseous hypertension and venous congestion in osteonecrosis of the knee.
AB  - To determine whether an angiogenic factor affects the pathogenesis of the
      idiopathic osteonecrosis of the medial femoral condyle, intraosseous pressure and
      venogram in 11 knees with osteonecrosis were compared with intraosseous pressure
      and venogram in 11 knees with the medial type of osteoarthritis. Patients were
      matched by age, gender, obesity index, blood pressure, tibiofemoral angle, and
      clinical evaluation. The intraosseous pressure of the medial condyle of the knees
      with osteonecrosis (62.8 +/- 27.3 mm Hg) was significantly higher than that in
      the lateral condyle of the knees with osteonecrosis (25.4 +/- 18.9 mm Hg) and
      those of both condyles of the knees with osteoarthritis (medial, 31.6 +/- 17.4 mm
      Hg; lateral, 29.5 +/- 11.0 mm Hg). In contrast, there was no significant
      difference in the pressure between the medial and lateral condyles of the knees
      with osteoarthritis. Venography showed a marked disturbance of venous drainage in
      all patients with osteonecrosis. In addition, the average clearance time of the
      medium in the medial femoral condyle was significantly more prolonged in patients
      with osteonecrosis (17.7 +/- 6.1 minutes) than in patients with osteoarthritis
      (5.5 +/- 1.6 minutes). These data support the hypothesis that venous stasis
      within the medullar canal in the condyle increases intraosseous pressure and
      decreases arteriovenous pressure difference, leading to osteonecrosis.

PMID- 11249169
TI  - Rotationplasty type B IIIa according to Winkelmann: electromyography and gait
      analysis.
AB  - After resection of a malignant bone tumor of the femur, rotationplasty is
      considered a treatment option in addition to other limb salvage procedures such
      as endoprosthetic replacement, allograft, or autograft reconstruction. A Type B
      IIIa rotationplasty is indicated when the tumor involves the total femur or when
      skip lesions are detected. After the total femur is resected, the lateral tibial
      plateau is placed into the acetabulum after rotating the tibia and foot segment
      180 degrees. Eight patients at an average age of 5.9 years underwent a
      rotationplasty Type B IIIa at the authors' institution. After a median followup
      of 59.6 months (range, 24-86 months) the clinical results were excellent and the
      functional status according to the criteria of the Musculoskeletal Tumor Society
      was good (23 of 30 points). In electromyographic analysis the muscle activity of
      the affected leg revealed good function of the stance and the swing phase muscles
      according to their new function with comparable amplitudes to the unaffected
      limb. The kinematics (range of motion of the hip and knee) were slightly
      assymmetric. Gait analysis showed a slight lateral trunk lean over the
      ipsilateral limb with reduced joint moment. All patients had full weightbearing
      ability. Remodeling of the tibial plateau into a round form mimicking a new
      femoral head is confirmed by radiographs and magnetic resonance imaging scans. In
      young children with a tumor of the total femur, rotationplasty Type B IIIa is a
      good treatment modality with excellent clinical and good functional results. The
      electromyographic and gait analysis data underscore a good functional restoration
      of gait after rotationplasty.

PMID- 11249170
TI  - Fractures of the capitellum: a new method of fixation using a maxillofacial
      plate.
AB  - Isolated capitellar fractures are rare, intraarticular fractures requiring an
      aggressive management regimen. Several treatment options have been described for
      the Type 1 fracture. A new technique of direct anatomic reduction and fixation of
      the fracture using a maxillofacial plate is reported. Advantages of this new
      technique are highlighted, and results with its use in treating patients of all
      ages are described.

PMID- 11249171
TI  - Snapping during manual stretching in congenital muscular torticollis.
AB  - Manual stretching frequently is used in the treatment of congenital muscular
      torticollis in infants. During manipulation, it is not uncommon for the
      sternocleidomastoid muscle to snap or suddenly give way. The main objective of
      this study was to evaluate the predisposing causes and clinical significance of
      such snapping. Four hundred fifty-five patients younger than 1 year of age with
      congenital muscular torticollis treated with a standardized gentle manual
      stretching program during a 13-year period were studied. Using prospective
      standardized assessment parameters, the pretreatment, treatment, and followup
      results of a group of 41 patients with snapping detected during treatment were
      compared with the results of a group of 404 patients without snapping during
      treatment. The group with snapping was associated with a more severe
      sternomastoid tumor, higher incidence of hip dysplasia, earlier clinical
      presentation, and shorter duration of treatment. With a mean followup of 3.5
      years, the group with snapping was not different from the group that had no
      snapping in the final assessment score and percentage requiring surgery. From
      this study, unintentional snapping during the gentle manipulation treatment of
      congenital muscular torticollis has clinical and ultrasonographic evidence of
      partial or complete rupture of the sternocleidomastoid muscle. No long-term
      deleterious effect on the outcome was observed after the snapping.

PMID- 11249172
TI  - Oblique wedge osteotomy for femoral diaphyseal deformity in fibrous dysplasia: a
      case report.
AB  - A patient with fibrous dysplasia who had a three-dimensional diaphyseal deformity
      in the left femur was treated using an oblique wedge osteotomy. The patient was
      26-year-old man with a history of two pathologic fractures in the midshaft of the
      femur. A 22 degrees angular deformity in the coronal plane and 15 degrees
      anterior bowing were corrected. The results at a followup 2 years after surgery
      were satisfactory in functional and radiologic terms. The technique and
      advantages of the oblique wedge osteotomy are discussed.

PMID- 11249173
TI  - Effect of rhythm and level of distraction on muscle structure: an animal study.
AB  - To determine the optimal rhythm of distraction and level of osteotomy for maximal
      muscle preservation during limb lengthening, histologic and ultrastructural
      analysis of the peroneus tertius muscle was performed in 46 goats. Thirty-nine
      animals with 20% or 30% tibial lengthening at the rate of 0.75 mm per day at each
      osteotomy level were divided in two groups. The first group included 15 animals
      undergoing tibial middiaphyseal lengthening with automated distractor producing
      one (n = 5), four (n = 5), or 720 (n = 5) increments per day. The second group
      included 24 animals in which lengthening was performed at the proximal (n = 4),
      middle (n = 6), distal (n = 6), or double (n = 8) level of the tibia with
      distraction rhythm of three times per day. The remaining seven animals served as
      controls. Histomorphologic features of the lengthened muscles were characterized
      by a polymorphous appearance with foci of necrosis, atrophy, and sclerosis
      scattered among apparently normal muscle fibers. The intensity and dispersion of
      degenerative changes were in direct proportion to the amount of lengthening but
      in reverse proportion to the frequency of distraction. Tibial lengthening at the
      diaphysis caused intense fibroblast proliferation and remarkable muscle
      sclerosis, whereas metaphyseal distraction was associated with a predominance of
      muscle tissue regeneration over atrophy and sclerosis. Bifocal lengthening and a
      more fractionated rhythm of distraction were associated with enhanced
      preservation of existing muscle fibers and greater regenerative activity of the
      muscle.

PMID- 11249174
TI  - Distraction laminoplasty for decompression of lumbar spinal stenosis.
AB  - Distraction laminoplasty is a technical modification of routine laminectomy that
      allows decompression of the lumbar spinal canal with maximal bone preservation.
      The technique involves the application of a distraction force, in conjunction
      with an undercutting laminoplasty technique. It is safe, easily applied, and
      allows excellent canal visualization and decompression with minimal bone
      resection. The purpose of the current study is to describe the technical aspects
      of the technique.

PMID- 11249175
TI  - Pulsed electromagnetic fields increase growth factor release by nonunion cells.
AB  - The mechanisms involved in pulsed electromagnetic field stimulation of nonunions
      are not known. Animal and cell culture models suggest endochondral ossification
      is stimulated by increasing cartilage mass and production of transforming growth
      factor-beta 1. For the current study, the effect of pulsed electromagnetic field
      stimulation on cells from human hypertrophic (n = 3) and atrophic (n = 4)
      nonunion tissues was examined. Cultures were placed between Helmholtz coils, and
      an electromagnetic field (4.5-ms bursts of 20 pulses repeating at 15 Hz) was
      applied to 1/2 of them 8 hours per day for 1, 2, or 4 days. There was a time
      dependent increase in transforming growth factor-beta 1 in the conditioned media
      of treated hypertrophic nonunion cells by Day 2 and of atrophic nonunion cells by
      Day 4. There was no effect on cell number, [3H]-thymidine incorporation, alkaline
      phosphatase activity, collagen synthesis, or prostaglandin E2 and osteocalcin
      production. This indicates that human nonunion cells respond to pulsed
      electromagnetic fields in culture and that transforming growth factor-beta 1
      production is an early event. The delayed response of hypertrophic and atrophic
      nonunion cells (> 24 hours) suggests that a cascade of regulatory events is
      stimulated, culminating in growth factor synthesis and release.

PMID- 11249176
TI  - An anatomic study of the supraspinatus muscle and tendon.
AB  - The gross and histologic anatomy of the myotendinous portion of the supraspinatus
      muscle was investigated with coronal and sagittal sections from 20 anatomic
      specimen shoulders. The anterior lateral portion of the supraspinatus contained
      more tendon than the posterior portion of the muscle in all 20 specimens. In
      seven specimens there were separate muscle fibers that originated from the most
      anteromedial area of the supraspinatus fossa. Knowledge of this anatomy aids in
      magnetic resonance image interpretation and open or arthroscopic evaluation of
      the supraspinatus. This consistent tendinous portion may be useful in rotator
      cuff repair and may provide a firm area for suture closure of the rotator
      interval. This prominent anterior tendinous area may serve to protect the
      supraspinatus during anterior forward flexion motion through the impingement arc.

PMID- 11249177
TI  - A radicular syndrome from developmental narrowing of the lumbar vertebral canal.
      1954.

PMID- 11249178
TI  - Treatment of spinal stenosis and fixed sagittal imbalance.
AB  - Most commonly, sagittal imbalance associated with stenosis is seen with a
      hypolordotic fusion mass, junctional kyphosis, and junctional stenosis. If the
      deformity is flexible, it can be treated with anterior and posterior fusion with
      anterior structural grafting. If it is fixed, which it usually is, then a pedicle
      subtraction procedure with decompression and extension of the fusion usually is
      the most suitable operative approach.

PMID- 11249179
TI  - Surgical treatment of patients with lumbar spinal stenosis with associated
      scoliosis.
AB  - Spinal stenosis in combination with scoliosis frequently is seen in elderly
      patients. Patients typically present with a combination of symptoms attributable
      to neurogenic claudication and radicular pain, and symptoms of lower back pain.
      For patients in whom conservative treatment is not sufficient, surgical treatment
      can be done with careful consideration of the overall patient and his or her
      medical status. Surgical treatment is twofold; one purpose is to decompress the
      neural elements, the other purpose is to stabilize and realign the spine to as
      great a degree as possible. Appropriate balance of the spine at the end of the
      procedure is more important than the absolute amount of correction obtained.
      Stabilization and correction of the spine is done with pedicle screw-rod
      instrumentation and fusion, and the procedure must be done in an efficient and
      timely manner to involve the least amount of morbidity. There are two types of
      deformity typically seen, one is a degenerative lumbar scoliosis with no or
      minimal rotational deformity (Type I), and the other is a degenerative scoliosis
      often superimposed on a preexisting scoliosis with greater rotational deformity
      and greater loss of lordosis (Type II). Instrumentation and correction techniques
      differ for these two types of deformities, with shorter instrumentation
      procedures usually possible for the Type I deformity and longer instrumentation
      with sagittal plane reconstitution necessary for Type II deformity.

PMID- 11249180
TI  - Lumbar stenosis with spondylolisthesis: current concepts of surgical treatment.
AB  - As degenerative changes progress in the aging population, more patients will
      present with degenerative spondylolisthesis. The clinical picture is usually of a
      woman older than 50 years of age with a degenerative lumbar spondylolisthesis at
      L5 with symptoms of neurogenic claudication or radiculopathy. Imaging studies
      will reveal a central recess, a lateral recess or both, and/or neuroforaminal
      stenosis. When patients do not respond to nonoperative treatments, surgical
      intervention is indicated. Most studies have concluded that the addition of an
      arthrodesis improves the clinical outcome. A recent longterm study showed that a
      solid fusion and an adequate decompression is the procedure offering the best
      outcome. The current authors will review the pathogenesis, clinical picture, and
      treatment recommendations for degenerative lumbar spondylolisthesis.

PMID- 11249181
TI  - Degenerative lumbar stenosis: the neurosurgical perspective.
AB  - Degenerative lumbar stenosis is a complex entity caused by predictable patterns
      of degenerative pathoanatomy. Patients with spinal stenosis are treated by
      orthopaedic surgeons and neurosurgeons, who often have slightly different ideas
      regarding treatment strategies. However, data exist to support several
      recommendations, regarding fusion with or without instrumentation, surgical
      versus conservative treatment, and limitation of procedures to symptomatic
      levels. In the current study, the typical patterns of degenerative disease and
      surgical treatment and a view of the neurosurgical perspective of the treatment
      of patients with lumbar stenosis are presented.

PMID- 11249182
TI  - Current techniques of decompression of the lumbar spine.
AB  - Lumbar spinal decompression is a commonly performed procedure. Although the
      conventional open techniques of decompression remain the gold standard of
      treatment, problems with paraspinal musculature denervation and resultant lumbar
      instability have focused attention on less invasive techniques. A multitude of
      spinal instrumentation systems have been developed to stabilize the spine and
      improve arthrodesis rates. A stronger emphasis on restoration of anterior column
      height and stability has increased the use of anterior interbody fusion devices.
      Developing technology is allowing for better visualization and possibly improved
      outcomes with minimally-invasive techniques. The results of all lumbar
      decompressive and stabilization procedures however, remain closely related to
      careful patient selection.

PMID- 11249183
TI  - Spinal cord and nerve root monitoring during surgical treatment of lumbar
      stenosis.
AB  - The author describes application of intraoperative neurophysiologic monitoring to
      surgical treatment of lumbar stenosis. Benefits of somatosensory and motor evoked
      potential studies during surgical correction of spinal deformity are well known
      and documented. Free-running and evoked electromyographic studies during pedicle
      screw implantation is an accepted practice at many institutions. However, the
      functional integrity of spinal cord, cauda equina, and nerve roots should be
      monitored throughout every stage of surgery including exposure and decompression.
      Somatosensory evoked potentials monitor overall spinal cord function.
      Intraoperative electromyography provides continuous assessment of motor root
      function in response to direct and indirect surgical manipulation.
      Electromyographic activities observed during exposure and decompression of the
      lumbosacral spine included complex patterns of bursting and neurotonic discharge.
      In addition, electromyographic activities at distal musculature were elicited by
      impacting a surgical instrument or graft plug against bony elements of the spine.
      All electromyographic events provided direct feedback to the surgical team and
      were regarded as a cause for concern. Simultaneously monitored evoked potential
      and electromyographic studies protect spinal cord and nerve roots during
      seemingly low-risk phases of a surgical procedure when neurologic injury may
      occur and the patient is placed at risk for postoperative myelopathy or
      radiculopathy.

PMID- 11249184
TI  - Phospholipase D (PLD) is present in Leishmania donovani and its activity
      increases in response to acute osmotic stress.
AB  - We report here that the signaling molecule phospholipase D (PLD) is present in
      the parasitic protozoan Leishmania donovani. In vitro enzymatic activity is
      dependent on Ca2+ and Mg2+ ions, its basal activity is stimulated by phosphatidyl
      inositol-4,5-bisphosphate (PIP2) and its pH optima are pH 8.0 and pH 6.0. PLD
      activity increases 3-fold about 5 min after an abrupt decrease in osmolality from
      317 mOsm (isosmotic) to 155 mOsm and increases 1.5-fold in response to an abrupt
      increase in osmolality to 617 mOsM. Cells grown for > 24 h under the anisosmotic
      conditions showed only marginal changes in activity compared to the controls
      grown under isosmotic conditions, indicating an adaptation to long-term exposure
      to hypo- or hyper-osmolarity. Immunologically, two isoforms, PLD1 and PLD2, are
      present. An analysis of in vitro PLD activity in anti-PLD immunocomplexes
      revealed that either hypotonic (cell swelling) or hypertonic stress (cell
      shrinking) causes an increase in PLD1 activation but a reduction in PLD2
      activity. The interplay between these two isoforms results in a predominance for
      PLD1 in the observed increase when measuring total PLD activity. Finally, the
      increase in enzymatic activity in acute hyposmotic shock is accompanied by
      tyrosyl phosphorylation of the PLD1 isoform, suggesting a role for protein
      tyrosine kinase in the control of PLD activity in response to osmotic stress.

PMID- 11249185
TI  - Encystation in Acanthamoeba castellanii: development of biocide resistance.
AB  - Since the early 1960s, axenic culture and the development of procedures for the
      induction of encystation have made Acanthamoeba spp. superb experimental systems
      for studies of cell biology and differentiation. More recently, since their roles
      as human pathogens causing keratitis and encephalitis have become widely
      recognized, it has become urgent to understand the parameters that determine
      differentiation, as cysts are much more resistant to biocides than are the
      trophozoites. Viability of trophozoites of the soil amoeba Acanthamoeba
      castellanii (Neff), is conveniently measured by its ability to form plaques on a
      lawn of Escherichia coli. Use of confocal laser scanning microscopy with
      Calcofluor white, Congo Red or the anionic oxonol dye, DiBAC4(3) or flow
      cytometry with propidium iodide diacetate and fluorescein or oxonol provides more
      rapid assessment. For cysts, the plaque method is still the best, because dye
      exclusion does not necessarily indicate viability and therefore the plate count
      method has been used to study the sequence of development of biocide resistance
      during the differentiation process. After two hours, resistance to HCl was
      apparent. Polyhexamethylene biguanide, benzalkonium chloride, propamidine
      isethionate, pentamidine isethionate, dibromopropamine isethionate, and H2O2 and
      moist heat, all lost effectiveness at between 14 and 24 h after trophozoites were
      inoculated into encystation media. Chlorhexidine diacetate resistance was
      observed at between 24 and 36 h. The molecular biology and biochemistry of the
      modifications that underlie these changes are now being investigated.

PMID- 11249186
TI  - Relationships of microsporidian genera, with emphasis on the polysporous genera,
      revealed by sequences of the largest subunit of RNA polymerase II (RPB1).
AB  - Molecular data have proved useful as an alternative to morphological data in
      showing the relationships of genera within the phylum Microsporidia, but until
      now have been available only for ribosomal genes. In previous studies protein
      coding genes of microsporidia have been used only to assess their position in the
      evolution of eukaryotes. For the first time we report on the use of a protein
      coding gene, the A-G region of the largest subunit of RNA polymerase II (RPB1)
      from 14 mainly polysporous species, to generate an alternative phylogeny for
      microsporidia. Using the amino acid sequences, the genera and species fell into
      the same main groupings as had been obtained with 16S rDNA sequences, but the
      RPB1 data provided better resolution within these groups. The results supported
      the pairings of Trachipleistophora hominis with Vavraia culicis and Pleistophora
      hippoglossoideos with Pleistophora typicalis. They also confirmed that the genus
      Pleistophora is not monophyletic and that it will be necessary to transfer
      Pleistophora ovariae and Pleistophora mirandellae into one or more other genera,
      as has already been effected for Pleistophora anguillarum.

PMID- 11249187
TI  - Gametogenesis, fertilization and ookinete differentiation of Leucocytozoon
      smithi.
AB  - Development of Leucocytozoon smithi during gametogenesis, fertilization, and
      ookinete differentiation was studied by light and electron microscopy.
      Gametogenesis occurred rapidly, within 1-2 min after gametocytes were ingested by
      black flies. Usually one axoneme, but not infrequently two, was observed in
      microgametes. The macrogamete nucleus was characteristically elongated and
      fragmented, with a convoluted nuclear envelope. Fertilization occurred within
      five min after ingestion of gametocytes by the vector. The entire axoneme and
      nucleus of the microgamete entered the cytoplasm of the macrogamete. Zygote
      differentiation resembled sporozoite formation in that a thickened inner membrane
      and subpellicular microtubules developed beneath the plasmalemma, followed by
      cytoplasmic protrusion or evagination to form the anterior end. Extension of the
      inner thickened membrane continued as the zygote elongated. Development of
      sausage-shaped ookinetes was completed within 6-8 h after ingestion of a blood
      meal by a black fly. Mature ookinetes possessed a single nucleus, double-layered
      pellicle, canopy, apical pore, polar ring complex, subpellicular microtubules,
      micronemes, crystalloids, abundant mitochondria, endoplasmic reticulum, and
      ribosomes. Comparison of development of L. smithi with species of Plasmodium and
      Haemoproteus revealed general similarities in both sexual and asexual development
      within the insect vector. A diagram summarizing life cycle events for L. smithi
      is included.

PMID- 11249188
TI  - A role for a galactose lectin and its ligands during encystment of Entamoeba.
AB  - In the life cycle of Entamoeba parasites alternate between the colon-dwelling
      trophozoite and the infectious cyst forms. The physiologic stimuli that trigger
      differentiation of trophozoites into cysts remain undefined. On the surface of
      the human-infecting Entamoeba, parasites express a galactose/N
      acetylgatactosamine (gal/galNAc)-binding lectin, which plays demonstrated roles
      in contact-dependent lysis of target cells and resistance to host complement.
      Using a reptilian parasite, Entamoeba invadens, to study cyst formation in vitro,
      we found that efficient encystation was dependent on the presence of gal
      terminated ligands in the induction medium. Precise concentration ranges of
      several gal-terminated ligands, such as asialofetuin, gal-bovine serum albumin
      (gal-BSA), and mucin, functioned in encystation medium to stimulate
      differentiation. Greater than 10 mM levels of free gal inhibited the amoeba
      aggregation that precedes encystation and prevented formation of mature cysts.
      Inhibitory levels of gal also prevented the up-regulation of genes which normally
      occurs at 24 h of encystation. The surface of Entamoeba invadens was found to
      express a gal lectin which has a heterodimeric structure similar to that of
      Entamoeba histolytica. The 30 kDa light subunit (LGL) of the E. invadens lectin
      is similar in overall size and sequence to the LGL of E. histolytica. The heavy
      subunits, however, differ in size, have an identical spacing of cysteines in
      their extracellular domains, and have highly conserved C-terminal transmembrane
      and cytoplasmic domains. These results suggest a new role for the Entamoeba gal
      lectins in monitoring the concentrations of gal ligands in the colon and
      contributing to stimuli that induce encystment.

PMID- 11249189
TI  - Regulation of carbohydrate metabolism during Giardia encystment.
AB  - Giardia intestinalis trophozoites encyst when they are exposed to bile. During
      encystment, events related to the inducible synthesis of a novel N-acetyl-D
      galactosamine (GalNAc) homopolymer, occur. Within the first 6 h of encystment,
      mRNA for glucosamine 6-P isomerase (GPI), the first inducible enzyme unique to
      this pathway appears, oxygen uptake rates double from non-encysting levels, and
      metronidazole (MTZ) inhibits oxygen uptake. Within 12 h, GPI and its activity are
      detectable and OU decreases 50% from non-encysting levels; glucose's stimulation
      and MTZ's inhibition of oxygen uptake cease. In contrast, aspartate uptake
      remained constant throughout the 40 h monitored. Two genes, gpi 1 and 2 encode
      for GPI, but only gpi1 is expressed during encystment. Glucosamine 6-P (GlcN6P),
      the synthetic product of GPI, activates UDP-N-acetylglucosamine (UDP-GlcNAc)
      pyrophosphorylase, a downstream enzyme, 3 to 5-fold in the direction of UDP
      GlcNAc synthesis. UDP-GlcNAc is epimerized to UDP-GalNAc and UDP-GalNAc is
      polymerized by "cyst wall synthase" (beta 1 --> 3 GalNAc transferase) into a
      highly insoluble beta 1,3-linked homopolymer. This GalNAc polysaccharide, the
      major component of cyst wall filaments, forms, in conjunction with polypeptides,
      the outer cyst wall of Giardia.

PMID- 11249190
TI  - Phosphatidylinositol-specific phospholipase C (PI-PLC) cleavage of GPI-anchored
      surface molecules of Trypanosoma cruzi triggers in vitro morphological
      reorganization of trypomastigotes.
AB  - Trypanosoma cruzi trypomastigotes treated with phosphatidylinositol-specific
      phospholipase C (PI-PLC) in vitro are rapidly induced to differentiate into round
      forms. Using confocal microscopy, we were able to show that trypomastigotes
      treated with PI-PLC initiate the process of flagellum remodeling by 30 sec after
      contact with the enzyme and amastigote-like forms are detected as early as 10 min
      after PI-PLC treatment. Scanning and transmission electron microscopy indicate
      that trypomastigotes undergo a previously undescribed process of flagellum
      circularization and internalization. Analysis of the flagellar complex with
      monoclonal antibody 4D9 shows heterogeneous labeling among the parasites,
      suggesting a remodeling of these molecules. After PI-PLC treatment, parasites
      rapidly lose the surface marker Ssp-3 and 24 h post-treatment they begin to
      exhibit a circular nucleus and a rod-shaped kinetoplast. By flow cytometry
      analysis and confocal microscopy, the Ssp-4 amastigote-specific epitope can be
      detected on the parasite surface. This indicates that the release of
      trypomastigote GPI-anchored molecules by exogenous PI-PLC in vitro can trigger
      morphological changes.

PMID- 11249191
TI  - Behind the discovery of "Nissenbaum's fixative".
AB  - The author describes the serendipitous discovery, conception, development, and
      history of Nissenbaum's Fixative while an undergraduate biology major in the
      early 1950s. The subsequent uses, applications, and modifications over the past
      forty-seven years are also described. Some of the modifications omitted from his
      short original paper are mentioned. Highlights of his subsequent career in the
      field of medicine are noted.

PMID- 11249192
TI  - Fine structure of clonally propagated in vitro life stages of a Perkinsus sp.
      isolated from the Baltic clam Macoma balthica.
AB  - We established monoclonal in vitro cultures of a Perkinsus sp. isolated from the
      baltic clam Macoma balthica and compared morphological features of various life
      stages by light and transmission electron microscopy to those of the currently
      accepted Perkinsus species: Perkinsus marinus, Perkinsus olseni, Perkinsus
      atlanticus, and Perkinsus qugwadi. Except that trophozoites were slightly larger
      than those of P. marinus, and that they underwent zoosporulation in culture,
      observation of our isolate under light microscopy did not reveal striking
      differences from any Perkinsus species. Perkinsus sp. from M. balthica shared
      fine structural characteristics with other Perkinsus species that clearly place
      it within this genus. Although zoospores of Perkinsus sp. from M. balthica were
      slightly smaller than those from other species, the ultrastructural arrangement
      and appearance of the apical complex and flagella seem to be identical to those
      of P. marinus and P. atlanticus. Our isolate also appeared, in some sections, to
      have cortical alveolar expansions of the plasmalemma at regions other than the
      anterior end and lobulated mitochondria that were reported as unique for P.
      qugwadi. Little consensus exists among authors in the assignment of taxonomic
      weight to any particular morphological feature to designate Perkinsus species.
      The present study of gross morphology and ultrastructure was complemented with
      molecular studies reported elsewhere, which propose that Perkinsus sp. from
      Macoma balthica is a distinct species.

PMID- 11249193
TI  - Description of Perkinsus andrewsi n. sp. isolated from the Baltic clam (Macoma
      balthica) by characterization of the ribosomal RNA locus, and development of a
      species-specific PCR-based diagnostic assay.
AB  - A Perkinsus species was isolated from the baltic clam Macoma balthica and an in
      vitro culture established under conditions described for P. marinus. As reported
      previously, morphological features remarkable enough to clearly indicate that
      this isolate is a distinct Perkinsus species were lacking. In this study, regions
      of the rRNA locus (NTS, 18S, ITS1, 5.8S, and ITS2) of this isolate were cloned,
      sequenced, and compared by alignment with those available for other Perkinsus
      species and isolates. Sequence data from the rRNA locus and species-specific PCR
      assays indicated not only that Perkinsus sp. from M. balthica was not P. marinus,
      but it was different from P. atlanticus and P. olseni. The degree of difference
      was comparable to or greater than differences between accepted Perkinsus species.
      In particular, NTS sequence and length were dramatically different from that of
      P. marinus and P. atlanticus. Therefore, we formally propose to designate the
      Perkinsus sp. from M. balthica as a separate species, P. andrewsi n. sp. Primers
      based on P. andrewsi NTS sequence were used to develop a PCR-based diagnostic
      assay that was validated for species-specificity and sensitivity. PCR-based
      assays specific for either P. andrewsi or P. marinus were used to test for their
      presence in bivalve species sympatric to M. balthica. Although isolated from M.
      balthica, P. andrewsi was also detected in the oyster Crassostrea virginica and
      clams Macoma mitchelli and Mercenaria mercenaria, and could coexist with P.
      marinus in all four bivalve species tested.

PMID- 11249194
TI  - Morphological, biochemical and molecular characterization of Herpetomonas
      samuelpessoai camargoi n. subsp., a trypanosomatid isolated from the flower of
      the squash Cucurbita moschata.
AB  - We report the morphological, biochemical and molecular characteristics of a
      trypanosomatid isolated from the flower of Cucurbita moschata. Although the
      trypanosomatid was isolated from a plant, the lack of recognition of Phytomonas
      specific molecular markers based on spliced-leader and ribosomal genes as well as
      by monoclonal antibodies specific for Phytomonas argues against assigning it to
      this genus. Because the isolate displayed typical opisthomastigote forms in
      culture, it is assigned to the genus Herpetomonas. Analysis of randomly amplified
      polymorphic DNA (RAPD) patterns and characterization of ribosomal SSU and ITS
      markers suggest that it is more closely related to H. samuelpessoai than to any
      other species. However, the presence of spined flagellates in culture (displaying
      lateral expansions of the plasma membrane originating near the flagellar pocket)
      and isolate-specific RAPD fingerprints argue strongly that the trypanosomatid
      belongs to a new subspecies, for which the name Herpetomonas samuelpessoai
      camargoi n. subsp. is proposed.

PMID- 11249195
TI  - Divisional morphogenesis in Uroleptus caudatus (Stokes, 1886), and the
      relationship between the Urostylidae and the Parakahliellidae, Oxytrichidae, and
      Orthoamphisiellidae on the basis of morphogenetic processes (Ciliophora,
      Hypotrichida).
AB  - Morphogenetic processes during division in Uroleptus caudatus (Stokes, 1886) are
      described using protargol impregnation. As is typical for the family Urostylidae
      Butschli, 1889, zigzag midventral cirri develop, but contrary to most species of
      this family the adoral membranelles of the proter are not renewed during division
      and two dorsomarginal kineties develop. These two atypical features occur in only
      two other species of the Urostylidae (Uroleptus musculus, Holosticha diademata),
      and in all species of the family Parakahliellidae Eigner. 1997, and in many of
      the Oxytrichidae Ehrenberg, 1838. Membranelles are also not renewed in the
      Orthoamphisiellidae Eigner, 1997. This shows that these three atypical members of
      the family Urostylidae are those which are most closely related to the other
      three hypotrichous families named above. The highly distinct zigzag midventral
      cirri clearly separate the family Urostylidae from the other three hypotrichous
      families. These cirri are used together with new morphogenetic features for a
      revised family diagnosis. The analysis of the Urostylidae revealed that during
      division all species of the family Urostylidae develop their cirral patterns,
      including the two rightmost ventral anlagen, in separate areas for each proter
      and opisthe. Thus, "long primary primordia" are absent in the Urostylidae. This
      is similar to the morphogenetic pattern by which the family Parakahliellidae is
      defined ("neokinetal 1") indicating that the Urostylidae are more closely related
      to the Parakahliellidae than to either the Oxytrichidae or to the
      Orthoamphisiellidae. All 68 detailed descriptions of divisional morphogenesis in
      species of the Hypotrichida are analyzed now in this and two former papers. As a
      result all these species can be assigned or at least recognized to be closely
      related to one of the following four families: to the Orthoamphisiellidae
      ("within-row" anlagen), to the Oxytrichidae ("neokinetal 3" anlagen), to the
      Parakahliellidae ("neokinetal 1" anlagen), and to the distinctly different
      Urostylidae ("midventral" anlagen). Thus, all Hypotrichida can most probably be
      assigned after morphogenetic investigation to one of the four families.

PMID- 11249196
TI  - Analysis of micronuclear, macronuclear and cDNA sequences encoding the regulatory
      subunit of cAMP-dependent protein kinase of Euplotes octocarinatus: evidence for
      a ribosomal frameshift.
AB  - We have isolated and characterized the micronuclear gene encoding the regulatory
      subunit of cAMP-dependent protein kinase of the ciliated protozoan Euplotes
      octocarinatus, as well as its macronuclear version and the corresponding cDNA.
      Analyses of the sequences revealed that the micronuclear gene contains one small
      69-bp internal eliminated sequence (IES) that is removed during macronuclear
      development. The IES is located in the 5'-noncoding region of the micronuclear
      gene and is flanked by a pair of tetranucleotide 5'-TACA-3' direct repeats. The
      macronuclear DNA molecule carrying this gene is approximately 1400 bp long and is
      amplified to about 2000 copies per macronucleus. Sequence analysis suggests that
      the expression of this gene requires a +1 ribosomal frameshift. The deduced
      protein shares 31% identity with the cAMP-dependent protein kinase type I
      regulatory subunit of Homo sapiens, and 53% identity with the regulatory subunit
      R44 of one of the two cAMP-dependent protein kinases of Paramecium. In addition,
      it contains two highly conserved cAMP binding sites in the C-terminal domain. The
      putative autophosphorylation site ARTSV of the regulatory subunit of E.
      octocarinatus is similar to that of the regulatory subunit R44 of Paramecium but
      distinct from the consensus motif RRXSZ of other eukaryotic regulatory subunits
      of cAMP-dependent protein kinases.

PMID- 11249197
TI  - Reconstruction of the flagellar apparatus in Ploeotia costata (Euglenozoa) and
      its relationship to other euglenoid flagellar apparatuses.
AB  - The flagellar apparatus of Ploeotia costata Farmer and Triemer was reconstructed
      using serial sectioning and TEM. The flagellar apparatus is similar to other
      euglenoids having two flagella arising from basal bodies connected by a striated
      fiber, and three asymmetrically arranged roots. The flagella emerge subapically
      from between the two ventral pellicle strips. The dorsal flagellum is 1/2 the
      body length and actively pulls the cell, while the ventral flagellum is twice the
      body length and drags along the substrate surface. The ventral and dorsal roots
      are on the opposite sides of their respective basal bodies, while the
      intermediate root is associated with the ventral flagellum on the side closest to
      the dorsal basal body. The dorsal root lines the dorsal side of the reservoir and
      after giving rise to the dorsal band lines the right side of the reservoir/canal.
      The ventral and intermediate roots join at the reservoir forming the intermediate
      ventral root, which lines the left and ventral sides of the reservoir/canal.
      There was no evidence of a microtubule-reinforced pocket in P. costata.
      Comparisons with Ploeotia vilrea, Lentomonas applanatum, and related flagellar
      apparatuses led to the conclusion that the basic euglenoid flagellar structure is
      symplesiomorphic but with enough variation to be taxonomically diagnostic.

PMID- 11249198
TI  - Trichites of Strombidium (Ciliophora, Oligotrichida) are extrusomes.
AB  - The trichites of Strombidium and related genera have been considered either as a
      cytoskeletal armature or as extrusomes. To demonstrate their true nature, a study
      was undertaken on two marine Strombidium species by ultrastructural and
      cytochemical analysis as well as in vivo experiments. Trichites, extending from
      the cortex into the cell, are rod-shaped, membrane-bounded, and have a complex
      structure. The following elements of the trichites, are distinguishable: an
      electron-transparent lumen, a laminated layer, and a compact layer. In trichites
      of one species, thin "rings" surround the lumen. Numerous short, curved tubules
      with a polysaccharide wall are present in the cytoplasm surrounding the
      trichites. At the cortical end, each trichite is enveloped by a "cap" of electron
      dense proteinaceous material. In some cases, the cortical alveoli appear
      interrupted, forming a "hole" for trichite ejection. Ejection of rod-shaped
      structures, up to 5 times longer than resting trichites, was obtained by in vivo
      treatments with dextran and aminoethyldextran. Negative staining indicated that
      these structures were transformed trichites. As no other possible extrusive
      structures were observed in the cytoplasm of Strombidium, trichites were
      considered extrusomes.

PMID- 11249199
TI  - Cardiotoxicity studies using freshly isolated calcium-tolerant cardiomyocytes
      from adult rat.

PMID- 11249200
TI  - Contraction of fibroblast-containing collagen gels: initial collagen
      concentration regulates the degree of contraction and cell survival.
AB  - Remodeling of extracellular matrix involves a number of steps including the
      recruitment, accumulation, and eventual apoptosis of parenchymal cells as well as
      the production, organization, and rearrangement of extracellular matrix produced
      by these cells. The culture of fibroblasts in three-dimensional gels made of type
      I collagen has been used as a model of tissue contraction which characterizes
      both wound repair and fibrosis. The current study was designed to determine the
      effect of initial collagen concentration on the ability of fibroblasts to
      contract collagen gels and on cell survival. Native type I collagen was extracted
      from rat tail tendons and used to prepare collagen gels with varying collagen
      concentrations (0.75-2.0 mg/ml). Human lung fibroblasts (HFL-1) were cast into
      the gels and cultured in Dulbecco modified Eagle medium with 0.1% fetal calf
      serum for 2 wk. The gel size, collagen content, and deoxyribonucleic acid (DNA)
      content were determined. Gels prepared with an initial concentration of 0.75
      mg/ml contracted more rapidly and to a smaller final size than gels prepared from
      2 mg/ml initial collagen concentration (final size 7.1 versus 36.4% of initial
      size, P < 0.01). There was no significant degradation of the collagen in the gels
      under either condition. Hence, the dramatically increased contraction of the
      lower density gels resulted in a higher final density (P < 0.01). Cell density
      was estimated from DNA content. In low initial density gels, the final DNA
      content was significantly less than that in higher initial density gels (0.73
      versus 1.88 microg/gel, P < 0.05). This was accompanied by an increased
      percentage of apoptotic cells at day 14 (43.3 versus 34.1%, P < 0.05). If the
      gels were maintained in the attached state which largely prevents contraction,
      apoptosis was significantly reduced, suggesting that contraction rather than
      matrix composition was a requirement for the increased apoptosis. In summary,
      these findings indicate that the initial matrix composition can lead to differing
      outcomes during fibroblast-mediated wound contraction.

PMID- 11249201
TI  - Characterization of a new rat cell line established from 2'AAF-induced combined
      hepatocellular cholangiocellular carcinoma.
AB  - A rat cell line-nominated CC-62 derived from a combined hepatocellular and
      cholangiocellular carcinoma obtained by administration of 2-acetylaminofluorene
      to male Wistar rats, has been established. Using light and electron microscopy it
      was determined that morphologically the tumor consisted of a mixed population of
      hepatocytes and cholangiolar neoplastic cells, intermingled with small,
      undifferentiated oval-like cells. The CC-62 line has been maintained through 90
      passages in culture adopting a paving stone arrangement. Doubling time at the
      12th passage was 23 h. Immunostaining with a panel of antisera was performed to
      identify the cytological profiles of the cell line. There was no k-ras or p53
      expression by immunohistochemistry, and molecular biology failed to detect
      mutations. Molecular analysis by reverse transcriptase-polymerase chain reaction
      revealed transcripts for c-met but no expression of HGF messenger ribonucleic
      acid. Three cell lines cloned from CC-62 showed the same immunohistochemical and
      molecular pattern as the parental line. Cytogenetic analysis revealed a
      chromosome number ranging from 74 to 82 with a modal number of 79 but no clonal
      structural abnormalities were found. Deoxyribonucleic acid ploidy analysis showed
      an aneuploid peak. CC-62 caused tumors 1 mo after subcutaneous transplantation
      into nude mice, with morphological patterns of mucosecretory solid and spindle
      shaped carcinoma. This cell line is the first established from a primary rat
      combined hepatocellular and cholangiocellular neoplasm. The resulting cells
      expressed biological and morphological markers of hepatocytes and cholangiolar
      cells. Therefore this cell line may contribute to a better understanding of the
      histogenesis of liver cancer.

PMID- 11249202
TI  - Monitoring of ascorbate at a constant rate in cell culture: effect on cell
      growth.
AB  - Ascorbic acid (vitamin C) is a primary antioxidant for cells. But, ascorbic acid
      added to culture medium is not readily available to cells in culture, because it
      is unstable in aqueous media. We determined the conditions required to obtain and
      maintain a constant concentration of ascorbate in the culture medium using
      ascorbate and ascorbate-phosphate. The study was carried out with human
      fibroblasts and the amounts of ascorbate in the culture medium were determined by
      high performance liquid chromatography. A mixture of 0.25 mmol/L ascorbate and
      0.45 mmol/L ascorbate-phosphate provided a constant concentration of ascorbate in
      the culture medium. This constant ascorbate concentration proved to be nontoxic
      for cells and stimulated cell growth in the short term and long term.

PMID- 11249203
TI  - Dome formation and tubule morphogenesis by Xenopus kidney A6 cell cultures
      exposed to microgravity simulated with a 3D-clinostat and to hypergravity.
AB  - Confluent high-density cell cultures of A6 cells derived from adult male Xenopus
      kidney exhibit spontaneous dome-formation at 1 g. To determine whether this
      morphogenetic property is altered by gravity, we used a three-dimensional (3D)
      clinostat to subject the cells to simulated microgravity, and a centrifuge to
      subject them to hypergravity. We used the generation orbit control method as the
      new rotation control system of the 3D-clinostat, not the random method. The
      growth of A6 cells was significantly enhanced by hypergravity, but significantly
      reduced by simulated microgravity. Dome formation by A6 cells at high confluence
      was inhibited under simulated microgravity conditions, whereas hypergravity
      promoted dome formation and induced tubule morphogenesis, compared to the control
      at 1 g. These results indicated that changes in gravity influence the
      morphogenetic properties of A6 cells, such as dome formation and tubule
      morphogenesis. When dome formation by A6 cells at high confluence was induced
      spontaneously in the control 1 g culture, the gene expression of the HGF family
      of pleiotropic factors, such as HGF-like protein (HLP) and growth factor
      Livertine (GF-l.ivertine), an epithelial serine protease of channel activating
      protease 1 (CAP1), and Na+, K+-adenosine triphosphatase (ATPase), increased.
      Simulated microgravity increased the gene expression of activin A and reduced the
      gene expression of HLP, GF-Livertine, CAP1, and Na+, K+-ATPase. Hypergravity, on
      the other hand, decreased the gene expression of activin A and increased the gene
      expression of HLP, GF-Livertine, CAP1, and Na+, K+-ATPase. These results suggest
      that the effects of gravitational changes on expression of the HGF family member
      gene, CAP1, and Na+, K+-ATPase gene may be important for the cell growth, tubule
      morphogenesis, and dome formation of A6 cells in altered

PMID- 11249204
TI  - Regulation of retinal capillary cells by basic fibroblast growth factor, vascular
      endothelial growth factor, and hypoxia.
AB  - Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor
      (bFGF) feature prominently in retinal neovascular diseases. Although the role of
      VEGF in retinal angiogenesis is well established, the importance of bFGF in this
      process requires further clarification. This study was undertaken to investigate
      the responses of retinal capillary cells (endothelial cells and pericytes) to
      bFGF under hypoxic conditions, as well as the potentially synergistic effects of
      bFGF and VEGF on the proliferation and cord formation of retinal endothelial
      cells. Cell proliferation was determined by cell number and by 3H-thymidine
      incorporation. Cord formation was assessed in three-dimensional gels of collagen
      type I. VEGF and bFGF increased 3H-thymidine incorporation by both cell types, an
      effect that was more pronounced in a hypoxic environment. Moreover, the
      proliferation of pericytes was stimulated to a greater extent by bFGF relative to
      VEGF. Endothelial migration in collagen gels, however, was induced more
      effectively by VEGF than by bFGF. A synergistic effect of VEGF and bFGF on cell
      invasion was observed in the collagen gel assay. VEGF and bFGF each augment
      proliferation of these cells, especially under hypoxia. We thus propose that
      these two cytokines have a synergistic effect at several stages of angiogenesis
      in the retina.

PMID- 11249205
TI  - Optimal production and in vitro activity of recombinant endostatin from stably
      transformed Drosophila melanogaster S2 cells.
AB  - Recombinant plasmids containing a complementary deoxyribonucleic acid coding
      mouse endostatin were transfected and stably expressed in Drosophila melanogaster
      Schneider 2 (S2) cells. Stably transformed polyclonal cell populations expressing
      recombinant endostatin were isolated after 4 wk of selection with hygromycin B.
      Recombinant endostatin expressed in the stably transformed S2 cells under the
      influence of the Drosophila BiP protein signal sequence was secreted into the
      medium. Recombinant endostatin was also purified to homogeneity using a simple
      one-step Ni2+ affinity fractionation method. Purified recombinant endostatin
      inhibited endothelial cell proliferation in a dose-dependent manner. The
      concentration at maximum inhibition for recombinant endostatin was approximately
      1.8 microg/ml. The stably transformed S2 cells produced 18 mg recombinant
      endostatin/L 7 d after induction with 5 microM CdCl2. Sodium butyrate
      supplementation (2.5 mM) increased recombinant endostatin production by 17%.
      These findings demonstrate optimal production and in vitro activity of
      recombinant endostatin from stably transformed D. melanogaster S2 cells.

PMID- 11249206
TI  - Pleiotropic effects of corticotropin releasing hormone on normal human skin
      keratinocytes.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis is the major stress response
      system. Several components of the HPA axis, such as corticotropin-releasing
      hormone (CRH) and POMC peptides and their receptors are also present in the skin.
      In earlier studies, we showed that CRH inhibits cellular proliferation of
      immortalized human keratinocytes. We now examine further the functional activity
      of the HPA axis in the skin, by characterizing the actions of CRH on normal
      foreskin keratinocytes. The CRH receptor was detected as CRH-R1 antigen at 47 kDa
      in the cultured keratinocytes by Western blotting, and immunohistochemistry
      demonstrated its presence in the epidermal and follicular keratinocytes. CRH is
      also biologically active in cultured keratinocytes, where it inhibits
      proliferation and enhances the interferon-gamma-stimulated expression of the hCAM
      and ICAM-1 adhesion molecules and of the HLA-DR antigen. These effects were
      concentration-dependent, with maximal activity at CRH 10(-7) M. Thus, in the
      keratinocyte, the most important cellular component of the epidermis, CRH appears
      to induce a shift in energy metabolism away from proliferation activity, and
      toward the enhancement of immunoactivity. Therefore, similar to its central
      actions, cutaneous CRH may also he involved in the stress response, but at a
      highly localized level.

PMID- 11249207
TI  - Development and application of computer software for cell culture laboratory
      management.
AB  - Prototype computer software for a Cell Culture Laboratory Management System
      (CCLMS) has been developed to relieve cell culture specialists of the burden of
      manual recordkeeping. Conventional data archives in cell culture laboratories are
      prone to error and expensive to maintain. The reliance upon cell culture to
      provide models for biochemical and molecular biological research serves to
      magnify errors at great expense. The CCLMS prototype encapsulates a modular
      software application that manages the many aspects of cell culture laboratory
      recordkeeping. A transaction-based database stores detailed information on
      subcultures, freezes and thaws, prints waterproof labels for culture vessels, and
      provides for immediate historical trace-back of any cultured cell line. Linked
      database files store information specific to an individual culture flask while
      removing redundancy between similar groups of flasks. A frozen cell log maintains
      locations of all vials within any type of cryogenic storage unit, locates spaces
      for newly frozen cell lines, and generates alphabetical or numerical reports.
      Finally, modules for maintaining cell counts, user records, and culture vessel
      specifications to support a comprehensive automation process are incorporated
      within this software. The developed CCLMS prototype has been demonstrated to be
      an adaptable, reliable tool for improving training, efficiency, and historical
      rigor for two independent cell culture facilities.

PMID- 11249208
TI  - Flexural and torsional stiffness in multi-jointed biological beams.
AB  - Flexibility, the ability to deform in response to loads, is a common property of
      biological beams. This paper investigates the mechanical behavior of multi
      jointed beams, which are characterized by a linear series of morphologically
      similar joints. Flexural stiffness and torsional stiffness were measured in two
      structurally distinct beams, crinoid arms (Echinodermata, Comatulida) and
      crustacean antennae (Arthropoda, Decapoda). Morphological data from these beams
      were used to determine the relative contributions of beam diameter and joint
      density (number of joints per millimeter of beam length) to the flexural and
      torsional stiffness of these two structures. As predicted by beam theory, beam
      diameter influenced stiffness in both crinoid arms and crustacean antennae. In
      crinoid arms, increases in joint density were associated with decreases in
      stiffness, but joint density had no significant influence on stiffness in
      crustacean antennae. In both crinoid arms and crustacean antennae, the magnitudes
      of flexural and torsional stiffness, as well as the ratio of these two variables,
      were similar to previously reported values for non-jointed biological beams.
      These results suggest that the structural design of a biological beam is not a
      limiting factor determining its mechanical properties.

PMID- 11249209
TI  - Metamorphosis of coeloblastula performed by multipotential larval flagellated
      cells in the calcareous sponge Leucosolenia laxa.
AB  - The calcareous sponge Leucosolenia laxa releases free-swimming hollow larvae
      called coeloblastulae that are the characteristic larvae of the subclass
      Calcinea. Although the coeloblastula is a major type of sponge larva, our
      knowledge about its development is scanty. Detailed electron microscopic studies
      on the metamorphosis of the coeloblastula revealed that the larva consists of
      four types of cells: flagellated cells, bottle cells, vesicular cells, and free
      cells in a central cavity. The flagellated cells, the principal cell type of the
      larva, are arranged in a pseudostratified layer around a large central cavity.
      The larval flagellated cells characteristically have glutinous granules that are
      used as internal markers during metamorphosis. After a free-swimming period the
      larva settles on the substratum, and settlement apparently triggers the
      initiation of metamorphosis. The larval flagellated cells soon lose their
      flagellum and begin the process of dedifferentiation. Then the larva becomes a
      mass of dedifferentiated cells in which many autophagosomes are found. Within 18
      h after settlement, the cells at the surface of the cell mass differentiate to
      pinacocytes. The cells beneath the pinacoderm differentiate to scleroblasts that
      form triradiate spicules. Finally, the cells of the inner cell mass differentiate
      to choanocytes and are arranged in a choanoderm that surrounds a newly formed
      large gastral cavity. We found glutinous granules in these three principal cell
      types of juvenile sponges, thus indicating the multipotency of the flagellated
      cells of the coeloblastula.

PMID- 11249210
TI  - Interspecific relationships between egg size and the level of parental investment
      per offspring in echinoderms.
AB  - The relationship between the size of an egg and its energy content was analyzed
      using published data for 47 species of echinoderms. Scaling relationships were
      evaluated for all species, as well as for subsets of the species, based on mode
      of development. Regressions were calculated using linear, power function, full
      allometric, and second-order polynomial models. The full allometric model is
      preferred because it is relatively simple and the most general. Among these
      species of echinoderms, larger eggs contain more energy. Egg energy content
      scales isometrically across a wide range of egg sizes both among and within
      different modes of development. The only exception is among species with feeding
      larval development, where there does not seem to be a clear scaling relationship.
      In most cases, the regressions were statistically significant and explained a
      very large proportion of the variance in energy content. However, there were wide
      confidence intervals around the estimated regression parameters. In all cases,
      the predictive power of the regression was poor, requiring large differences in
      egg size to yield significantly different predictions of energy content.
      Consequently, egg size is of limited value for the quantitative prediction of egg
      energy content and should be used with caution in life-history studies.

PMID- 11249211
TI  - The adaptive bleaching hypothesis: experimental tests of critical assumptions.
AB  - Coral bleaching, the loss of color due to loss of symbiotic zooxanthellae or
      their pigment, appears to be increasing in intensity and geographic extent,
      perhaps related to increasing sea surface temperatures. The adaptive bleaching
      hypothesis (ABH) posits that when environmental circumstances change, the loss of
      one or more kinds of zooxanthellae is rapidly, sometimes unnoticeably, followed
      by formation of a new symbiotic consortium with different zooxanthellae that are
      more suited to the new conditions in the host's habitat. Fundamental assumptions
      of the ABH include (1) different types of zooxanthellae respond differently to
      environmental conditions, specifically temperature, and (2) bleached adults can
      secondarily acquire zooxanthellae from the environment. We present simple tests
      of these assumptions and show that (1) genetically different strains of
      zooxanthellae exhibit different responses to elevated temperature, (2) bleached
      adult hosts can acquire algal symbionts with an apparently dose-dependent
      relationship between the concentration of zooxanthellae and the rate of
      establishment of the symbiosis, (3) and finally, bleached adult hosts can acquire
      symbionts from the water column.

PMID- 11249212
TI  - Role of aerobic and anaerobic circular mantle muscle fibers in swimming squid:
      electromyography.
AB  - Circular mantle muscle of squids and cuttlefishes consists of distinct zones of
      aerobic and anaerobic muscle fibers that are thought to have functional roles
      analogous to red and white muscle in fishes. To test predictions of the
      functional role of the circular muscle zones during swimming, electromyograms
      (EMGs) in conjunction with video footage were recorded from brief squid
      Lolliguncula brevis (5.0-6.8 cm dorsal mantle length, 10.9-18.3 g) swimming in a
      flume at speeds of 3-27 cm s(-1). In one set of experiments, in which EMGs were
      recorded from electrodes intersecting both the central anaerobic and peripheral
      aerobic circular mantle muscles, electrical activity was detected during each
      mantle contraction at all swimming speeds, and the amplitude and frequency of
      responses increased with speed. In another set of experiments, in which EMGs were
      recorded from electrodes placed in the central anaerobic circular muscle fibers
      alone, electrical activity was not detected during mantle contraction until
      speeds of about 15 cm s(-1), when EMG activity was sporadic. At speeds greater
      than 15 cm s(-1), the frequency of central circular muscle activity subsequently
      increased with swimming speed until maximum speeds of 21-27 cm s(-1), when
      muscular activity coincided with the majority of mantle contractions. These
      results indicate that peripheral aerobic circular muscle is used for low,
      intermediate, and probably high speeds, whereas central anaerobic circular muscle
      is recruited at intermediate speeds and used progressively more with speed for
      powerful, unsteady jetting. This is significant because it suggests that there is
      specialization and efficient use of locomotive muscle in squids.

PMID- 11249213
TI  - Temperature effects on hemocyanin oxygen binding in an antarctic cephalopod.
AB  - The functional relevance of oxygen transport by hemocyanin of the Antarctic
      octopod Megaleledone senoi and of the eurythermal cuttlefish Sepia officinalis
      was analyzed by continuous and simultaneous recordings of changes in pH and
      hemocyanin oxygen saturation in whole blood at various temperatures. These data
      were compared to literature data on other temperate and cold-water cephalopods
      (octopods and giant squid). In S. officinalis, the oxygen affinity of hemocyanin
      changed at deltaP50/degrees C = 0.12 kPa (pH 7.4) with increasing temperatures;
      this is similar to observations in temperate octopods. In M. senoi, thermal
      sensitivity was much smaller (<0.01 kPa, pH 7.2). Furthermore, M. senoi
      hemocyanin displayed one of the highest levels of oxygen affinity (P50 < 1 kPa,
      pH 7.6, 0 degrees C) found so far in cephalopods and a rather low cooperativity
      (n50 = 1.4 at 0 degrees C). The pH sensitivity of oxygen binding (delta log
      P50/delta pH) increased with increasing temperature in both the cuttlefish and
      the Antarctic octopod. At low PO2 (1.0 kPa) and pH (7.2), the presence of a large
      venous oxygen reserve (43% saturation) insensitive to pH reflects reduced pH
      sensitivity and high oxygen affinity in M. senoi hemocyanin at 0 degrees C. In S.
      officinalis, this reserve was 19% at pH 7.4, 20 degrees C, and 1.7 kPa O2, a
      level still higher than in squid. These findings suggest that the lower metabolic
      rate of octopods and cuttlefish compared to squid is reflected in less pH
      dependent oxygen transport. Results of the hemocyanin analysis for the Antarctic
      octopod were similar to those reported for Vampyroteuthis--an extremely high
      oxygen affinity supporting a very low metabolic rate. In contrast to findings in
      cold-adapted giant squid, the minimized thermal sensitivity of oxygen transport
      in Antarctic octopods will reduce metabolic scope and thereby contribute to their
      stenothermality.

PMID- 11249214
TI  - Muscular alteration of gill geometry in vitro: implications for bivalve pumping
      processes.
AB  - In bivalves, water-pumping potential is determined both by ciliary activity and
      by the geometry of the system of passageways that acts as a conduit for water
      flow. Smooth muscles intrinsic to the gills of eulamellibranch bivalves possess
      the anatomical organization needed to regulate the dimensions of these water
      passageways. The tone of these muscles can be controlled experimentally using
      excitatory neurotransmitters to elicit muscle contraction and by removing Ca++
      from the Ringer's solution to induce muscular relaxation. These experimental
      methods were used to investigate the effects of smooth muscle tone on the gill
      dimensions of two freshwater bivalves, Dreissena polymorpha and Corbicula
      fluminea, and one marine bivalve, Mercenaria mercenaria. In addition, endoscopic
      observations were made from the suprabranchial chamber of a freshwater unionid,
      Lampsilis anodontoides. Contraction of gill muscles led to a significant
      reduction in interfilament width, internal ostial area, and the cross-sectional
      area of the water tubes. Endoscopic observation from minimally disturbed L.
      anodontoides revealed rapid constriction of the water tubes upon contraction of
      the muscles of the gill and gill axis. Taken together, these data support the
      idea that alteration of smooth muscle tone in the gill provides a mechanism for
      controlling water-pumping activities.

PMID- 11249215
TI  - Controlled field release of a waterborne chemical signal stimulates planktonic
      larvae to settle.

PMID- 11249216
TI  - Three-dimensional analysis of finlet kinematics in the chub mackerel (Scomber
      japonicus).
AB  - Finlets, which are small non-retractable fins located on the body margins between
      the second dorsal and anal fins and the caudal fin of scombrid fishes, have been
      hypothesized to improve swimming performance. The kinematics of three posterior
      finlets of the chub mackerel, Scomber japonicus, were examined using three
      dimensional measurement techniques to test hypotheses on finlet rigidity and
      function during steady swimming. Finlet bending and finlet planar orientation to
      the xz, yz, and xy planes were measured during steady swimming at 1.2 lengths s(
      1) in a flow tank. Despite very similar morphology among the individual finlets,
      there was considerable variability in finlet flexure during a stroke. Several of
      the finlets were relatively rigid and flat (with intrafinlet angles close to 180
      degrees during the stroke), although intrafinlet angle of the proximal portion of
      the most posterior finlet varied considerably over the stroke and was as low as
      140 degrees midstroke. Finlets showed complex orientations in three-dimensional
      space over a stroke, and these orientations differed among the finlets. For
      example, during tail deceleration the proximal portion of the fifth finlet
      achieves a mean angle of approximately 75 degrees with the xz plane, while the
      distal portion of this finlet is oriented at 110 degrees. Our data suggest that
      the trajectory of local water flow varies among finlets and that the most
      posterior finlet is oriented to redirect flow into the developing tail vortex,
      which may increase thrust produced by the tail of swimming mackerel.

PMID- 11249217
TI  - Molecular evidence for cryptic species of Aurelia aurita (Cnidaria, Scyphozoa).

PMID- 11249218
TI  - Operative treatment of ankle fractures: a minimum ten-year follow-up.
AB  - The long-term outcome of 25 patients with bimalleolar fractures of the ankle was
      assessed ten to fourteen years following their fractures using the Phillips
      scoring system. All patients had undergone open reduction and anatomical internal
      fixation (as described in their operative notes in the medical records). 52% of
      patients had a good or excellent overall outcome while 24% had a poor overall
      outcome. This study has the longest follow-up period (10 to 14 years) to date on
      the outcomes of internal fixation of bimalleolar ankle fractures and demonstrates
      a higher percentage of poorer outcomes than has been previously described. This
      trend appears to be predictable as other studies with shorter term follow-up have
      already established a trend of increasing radiological evidence of post-traumatic
      arthritis with successively longer-term outcome reports.

PMID- 11249219
TI  - Preliminary results comparing two methods of lateral column lengthening.
AB  - Forty-five patients (49 feet) underwent lateral column lengthening as treatment
      for painful pes planus. Twenty-five patients (27 feet) were available for both
      radiographic and clinical evaluation at least one year postoperatively. Of these
      25 patients, 10 feet underwent Evans opening wedge osteotomy with tricortical
      iliac crest bone graft; 17 feet underwent calcaneocuboid distraction arthrodesis
      utilizing iliac crest bone graft. In addition, both groups underwent debridement
      of the posterior tibial tendon combined with transfer of the flexor digitorum
      longus into the navicular for reinforcement. Radiographic results documented
      marked improvement in all parameters. There was more improvement in the
      calcaneocuboid fusion group than the osteotomy group, but the difference was not
      statistically significant. Postoperative AOFAS rating scores averaged 87.9 for
      the osteotomy group and 80.9 for the distraction arthrodesis group. The
      difference was not statistically significant. Twenty of 25 patients (83.5%) in
      both groups were very satisfied. Twenty-four of 25 patients (96%) stated that
      knowing the final result they would have the same surgery again. Complications
      were reported for 32 patients (34 feet). Both the Evans opening wedge calcaneal
      osteotomy and calcaneocuboid distraction arthrodesis offer significant
      improvement in the radiographic parameters and AOFAS clinical scores for patients
      with painful, flexible flatfoot deformity. However, the complication rate remains
      high with both methods, and the rate of nonunion and delayed union with the
      calcaneocuboid distraction arthrodesis method remains a significant problem with
      this technique.

PMID- 11249220
TI  - Calcaneal compartment syndrome after tibial fractures.
AB  - Compartment syndrome of the newly discovered calcaneal compartment of the foot is
      a theoretical possibility following tibial fracture due to the communication with
      the deep posterior compartment of the calf. Forty-nine patients were reviewed at
      least 18 months after open or closed tibial shaft fractures treated with tibial
      nailing in order to determine the prevalence of foot deformities secondary to
      previously undetected calcaneal or leg compartment syndromes. Ankle movements,
      foot height, length of feet and degree of clawing of the toes were all measured
      and compared with the unaffected opposite side. None of the patients complained
      of any symptoms from their feet and none had any significant foot deformities.
      Calcaneal compartment syndrome is rare after tibial fracture and routine
      measurement of calcaneal compartment pressures after such injuries is not
      indicated.

PMID- 11249221
TI  - The role of ankle arthroscopy on the surgical management of ankle fractures.
AB  - Nineteen patients were prospectively randomized for operative treatment of their
      ankle fracture to be supplemented with or without ankle arthroscopy. All patients
      had an SER or PER fracture with an intact medial malleolus requiring operative
      treatment without evidence of intra-articular debris preoperatively. All patients
      underwent plate fixation of their fibula fracture and had a similar postoperative
      protocol. Ten patients were randomized to the control group with plate fixation
      only and nine patients randomized to the plate fixation plus operative
      arthroscopy. The average follow-up was 21 months. The arthroscopic examination of
      the study group revealed eight of the nine patients to have articular damage to
      the dome of the talus. Minimal arthroscopic treatment of these joints was
      required. All patients healed their fractures. No difference was noted between SF
      36 scores or lower extremity scores between the two groups. At short-term follow
      up, it does not appear that the arthroscopic procedure will impact upon the
      patient's eventual outcome in this small group of patients.

PMID- 11249222
TI  - Collagenous fibril texture of the gliding zone of the human tibialis posterior
      tendon.
AB  - Light microscopy and scanning electron microscopy was used to describe the
      collagenous fibril texture of the wrap around region of the human tibialis
      posterior tendon in human cadavers. In the region where the tendon wraps around
      the medial malleolus, the anterior part of the tendon directed towards the pulley
      had the structure of fibrocartilage. This zone started approximately 25-30
      millimeters from the navicular insertion. Scanning electron microscopy of the
      collagen fibril texture revealed three different layers in the fibrocartilaginous
      zone. The anterior surface was covered by a meshwork of thin unbanded fibrils
      with a diameter of app. 30 nm. Beneath the superficial network there was an app.
      150 microm thick layer of banded collagen fibrils, These fibrils formed lamella
      like bundles which intersected at various angles. The main portion of the
      collagen fibrils lie below this layer and run in a longitudinal direction. The
      longitudinal fibrils were divided into bundles by loose connective tissue. The
      location of the fibrocartilage corresponds to the region where the tibialis
      posterior tendon wraps around the medial malleolus which serves as a pulley.
      CLINICAL SIGNIFICANCE: Our study documented the existence of a fibrocartilaginous
      zone with a specific collagen fibril texture that corresponds to a possible site
      of rupture, as reported by several authors. Due to special collagen fibril
      texture the fibrocartilage may be more vulnerable to repetitive tensile micro
      trauma.

PMID- 11249223
TI  - Effect of foot orthoses on rearfoot complex kinematics during walking gait.
AB  - The aim of this study was to quantify the effect of anti-pronatory and anti
      supinatory foot orthoses on the angular displacement, velocity and accelerations
      of the rearfoot complex during gait. The transverse plane motion of the leg
      relative to the foot was used to indicate rearfoot complex pronation and
      supination. Three dimensional gait analysis on 12 subjects was used to derive the
      changes in the rearfoot kinematics due to the orthoses. The anti-pronatory
      orthoses decreased the range of pronation during the contact phase (p=0.0002) and
      the total range of rearfoot complex motion (p=0.000002), whereas anti-supinatory
      orthoses increased the range of pronation during the contact phase (p=0.00006)
      and the total range of rearfoot motion (p=0.049). Anti-pronatory orthoses also
      decreased the initial peak in pronation velocity during the contact phase of gait
      (p=0.006). Neither orthosis had a statistically significant effect on rearfoot
      complex acceleration.

PMID- 11249224
TI  - Peroneus longus and brevis rupture in a collegiate athlete.
AB  - Peroneal tendon injuries should be considered in the differential diagnosis of
      lateral ankle pain and instability. The spectrum of injury to the peroneal
      tendons includes tenosynovitis, tendinitis, subluxation, dislocation and tears.
      The mechanism, presentation and treatment of isolated peroneal brevis and longus
      injuries has been described in the literature. This is a case study of a rare
      combined peroneus brevis and longus injury in a young healthy collegiate athlete.

PMID- 11249225
TI  - Trimalleolar fracture with a double fragment of the posterior malleolus: a case
      report and modified operative approach to internal fixation.
AB  - Fractures of the medial and lateral malleoli are frequently associated with
      fractures of the posterior malleolus, comprising trimalleolar fractures. The
      posterior fragment may be posteromedial or posterolateral and its size determines
      the necessity for surgical or non-surgical treatment. The authors describe a case
      of trimalleolar fracture with double involvement of the posterior malleolus, both
      a posteromedial and posterolateral fragment. A modified transmalleolar operative
      approach for internal fixation is recommended when dealing with such complex
      trimalleolar fractures of the ankle.

PMID- 11249226
TI  - Multiple hemangiomas of the foot: a case report.
AB  - Although hemangiomas are common soft tissue tumors, it rarely involves the feet.
      We are reporting a forty-seven-year-old female with multiple hemangiomas of her
      left foot without pain. During surgery there were seven well-defined masses that
      were totally excised after ligation of penetrating vessels. The microscopic
      investigation revealed mixed-type (capillary and cavernous) hemangioma. We had
      not experienced any recurrence after two years follow up period.

PMID- 11249227
TI  - MP I joint giving way--a case study.
AB  - A case history of a 26 year old international class female 400 m hurdle sprinter
      is presented. While sprinting she felt a sudden and very intensive pain at her
      left hallux. After this she was unable to run and had episodes of giving way in
      the MP I joint elicited by minor activity. Operative investigation revealed a
      broad disruption of the MP I medial collateral ligament. After periosteal flap
      repair and early functional aftertreatment she returned to full high level sports
      ability.

PMID- 11249228
TI  - Endoscopically assisted percutaneous achilles tendon suture.

PMID- 11249229
TI  - Where there's hope.
AB  - A young patient's account of her preoperative and postoperative experiences is
      recalled.

PMID- 11249230
TI  - Anatomical and radiological considerations of the fifth metatarsal bone.

PMID- 11249231
TI  - Hedonistic utilitarianism.

PMID- 11249232
TI  - Ankle arthrodesis: combined internal-external fixation.
AB  - This report documents the experience of using combined internal and external
      fixation in ankle arthrodesis. During the period from 1992 to 2000 a single
      surgeon used this method of fixation on 26 ankle fusions in 26 consecutive
      patients without exclusions. There were no nonunions and no delayed unions. The
      median time to union was 10.3 weeks and the mean time was 11.3 weeks (range, 7.4
      to 23.2 weeks). Complications specific to this procedure included 3 (12%) minor
      pin tract infections which cleared with oral, out-patient antibiotics, 4 (15%)
      skin irritations from internal fixation pins sufficiently bothersome to require
      pin removal after union was obtained, and 1 (4%) painful pin tract which cleared
      spontaneously. Most of these complications occurred early in the series and
      subsequent changes in technique considerably decreased their incidence. This
      fixation technique produced excellent results. Combined internal and external
      fixation is recommended as a useful option in arthrodesis of the ankle.

PMID- 11249233
TI  - First ray dorsal mobility in relation to hallux valgus deformity and first
      intermetatarsal angle.
AB  - The hypermobile first ray has been implicated as contributing to the cause and
      progression of hallux valgus deformity. Deformity of the hallux is often
      accompanied by an enlarged first intermetatarsal (IM 1-2) angle. It has been
      hypothesized that subjects having an abnormally large IM 1-2 angle have laxity of
      the first ray. Objectives of this study were to compare dorsal mobility of the
      first ray in subjects with hallux valgus to asymptomatic controls, and to
      investigate the relationship between dorsal mobility and the IM 1-2 angle.
      Fourteen subjects (age 23-81) with hallux valgus were matched by gender and age
      to control subjects. The IM 1-2 angle was measured from radiographs. A load-cell
      device measured dorsal mobility of the first ray under a standard load of 55 N.
      Pearson's correlation coefficient identified a marginal correlation (r = .51)
      between IM 1-2 angle and dorsal mobility. An independent t-test showed a
      statistically (P < 0.01) larger amount of dorsal mobility in the group of
      subjects having hallux valgus. Mobility of the first ray was increased in
      subjects with hallux valgus and a large IM 1-2 angle may be an indicator of
      increased dorsal mobility.

PMID- 11249235
TI  - Intra-abdominal desmoplastic small round cell tumor.
AB  - BACKGROUND: Intra-abdominal desmoplastic small round cell tumor is a rare
      malignancy with a predilection for young males. Unique histological and
      immunocytochemical features distinguish the tumor from other members of the
      family of small round cell tumors of infancy and childhood. The aggressive nature
      of tumor spread, relative insensitivity to chemotherapy, and generally incomplete
      resectability result in a very poor prognosis. The authors report a case of a 39
      year-old man with diffuse abdominal and pelvic involvement of intra-abdominal
      desmoplastic small round cell tumor treated with aggressive chemotherapy and
      surgery. METHODS: Computed tomography (CT)-guided biopsy of an omental mass was
      performed. Histologically, discrete nests of uniform closely packed malignant
      cells were distributed in a background of focally desmoplastic stroma.
      Immunocytochemistry demonstrated positivity for epithelial, mesenchymal, and
      neural markers. On the basis of these unique histological and immunohistochemical
      characteristics, the diagnosis of desmoplastic small round cell tumor was made.
      The patient was treated with aggressive neoadjuvant chemotherapy consisting of a
      high-dose alkylator -based combination regimen, followed by surgery. RESULTS: The
      patient had a 10 to 15 percent regression in tumor mass in response to
      chemotherapy. Laparotomy revealed two large omental masses, another large mass
      adherent to the left colon and pelvic sidewall, and diaphragmatic, peritoneal and
      mesenteric studding with small nodules. Complete surgical resection was not
      possible. CONCLUSIONS: Intra-abdominal desmoplastic small round cell tumor
      remains an aggressive malignancy with an extremely poor prognosis. Although some
      response to chemotherapy may be possible, complete resection is rare, and
      surgical efforts are generally palliative.

PMID- 11249234
TI  - Primary bony tumors of the pediatric spine.

PMID- 11249236
TI  - The marriage of art and science in health care.
AB  - This paper invites the reader to consider the marriage of art and science as
      antidote to much epidemic disease, for our greater personal and societal health.
      The history of arts medicine is reviewed, identifying its persisting although
      often tenuous link with health care from pre-history to the present. The author
      describes his personal encounter with art at the bedside, and how it led to his
      establishing a comprehensive artist-in-residence program at his university
      hospital. The scientific evidence underscoring the efficacy of art-making for
      physical and psychological health are outlined, together with the physiological
      and biochemical data. The author describes his own program, and offers examples
      of healing art in action.

PMID- 11249237
TI  - Mucocele of the appendix with hematuria.
AB  - Mucocele of the appendix, a nonspecific and descriptive term for an abnormal
      mucous accumulation within the appendiceal lumen, regardless of the underlying
      cause, is a rare clinical disease that is not usual as a consideration in the
      differential diagnosis of right lower quadrant lesions. The reported prevalence
      of mucocele of the appendix in appendectomy specimens is 0.2-0.3 percent.
      Hematuria due to mucocele of the appendix is extremely rare. Up to now, only few
      cases of such condition have been recorded in the literature. We describe a woman
      who experienced intermittent episodes of right lower quadrant pain and hematuria.
      Abdominal exploration incidentally displayed mucocele of the appendix. No
      evidence of other lesions was found. The patient was still in good health after
      operation. This case highlights mucocele of the appendix as a consideration in
      the differential diagnosis of right lower quadrant pain with hematuria.

PMID- 11249238
TI  - A patient care odyssey.

PMID- 11249239
TI  - Recordkeeping: helpful ways to reduce practice risk in the event of an audit.

PMID- 11249240
TI  - Understanding macular degeneration.

PMID- 11249241
TI  - Performing direct ophthalmoscopy.

PMID- 11249242
TI  - Photodynamic therapy of eye diseases.
AB  - Photodynamic therapy is presently being used to treat several cutaneous cancers.
      The production of new second generation photosensitizers with better absorption
      spectra and systemic tolerance has lead to active investigation of these
      compounds in ophthalmology. The selective tissue damage with PDT is achieved by
      sequestration of the photosensitizer in the target tissue and focal activation of
      the photosensitizer by low energy directed light. The potential uses for PDT
      include the treatment of ocular tumors, neovascularization and ciliary body
      ablation. Visudyne already has been approved by the FDA for the treatment of
      subfoveal choroidal neovascularization, and many patients already have been
      treated with this drug.

PMID- 11249243
TI  - Adjustable sutures in pediatric ophthalmology and strabismus.

PMID- 11249244
TI  - New options for eye cancer: alternatives to enucleation.

PMID- 11249245
TI  - Lens/cornea relationships: the key to fine-tuning soft lens fits.
AB  - Currently, it is rare to be unable to fit a patient with spherical soft lenses,
      and it is becoming increasingly easy to [figure: see text] achieve success with
      toric and other specialty lenses. If we fulfill the criteria of full corneal
      coverage, acceptable movement, overrefraction to a clear end point, and stable,
      nonfluctuating visual acuity, our patients should be well on their way to long
      term success with soft lenses.

PMID- 11249246
TI  - "Why I chose to become a nurse and why I chose this school".

PMID- 11249247
TI  - The art of getting what you want for optimal patient care.
AB  - Getting your way is a mix of logical and emotional issues. It is important to
      establish rapport and meet a person emotionally before trying to sell an idea. It
      is essential to think an idea through clearly ahead of time and to present it
      clearly and logically. The possibility of resistance should be anticipated so
      that the presentation addresses potential areas of resistance. It is important to
      actively listen, to agree when possible, and to not appear too eager. Persuasion
      is both an art and science. When used skillfully, persuasive techniques are
      powerful tools of communication and productivity.

PMID- 11249248
TI  - How often do high school guidance counselors suggest practical nursing as a
      career option?
AB  - The Centre for Nursing Studies provides practical nursing education in
      Newfoundland and Labrador. Because applications to the program from direct high
      school students were consistently low, in 1999 the Centre for Nursing Studies
      surveyed the provincial high school guidance counselors to determine their
      perceived knowledge level of the roles and responsibilities of Licensed Practical
      Nurses and the practical nursing program, the number of times they suggested
      practical nursing to students and characteristics they believed to be necessary
      for a practical nurse. There were 168 questionnaires distributed. Fifty (30%)
      returned questionnaires were analyzed. The results demonstrated that the majority
      of guidance counselors (66%) receive between 1 to 5 requests for information
      regarding practical nursing annually. Forty-eight percent suggest practical
      nursing as a career option 1 to 5 times annually, while an additional 22% suggest
      it 6 to 10 times. Some of the characteristics identified, by the guidance
      counselors, to be necessary for practical nurses include good people skills,
      empathy, hard working, good communication skills, a desire to help others and an
      interest in health care.

PMID- 11249249
TI  - Self care for nurses: an integral part of patient care.

PMID- 11249250
TI  - Considerations in "caring" when your client is elderly.

PMID- 11249251
TI  - National Service Framework for coronary heart disease: challenges and
      opportunities.

PMID- 11249252
TI  - The development of an academic rated induction programme in a high dependency
      unit.
AB  - The commissioning of a new high dependency unit in a large district general
      hospital prompted the need to develop a comprehensive structured induction
      programme. A simple training needs analysis (TNA) tool was developed and used to
      assess the training requirements of 12 nurses who would make up the team. The
      results of the TNA gave an indication of where to channel resources into a month
      long induction programme. The programme was linked to the outcomes of a diploma
      module to ease the processes of accreditation of prior learning (APL) for those
      who chose to access higher education programmes beyond the duration of the
      induction. The programme was evaluated positively and is seen as a way forward
      for the future of flexible, accessible, practice-based, continuing professional
      development opportunities.

PMID- 11249253
TI  - Nurse-led weaning from ventilation and extubation in the paediatric
      cardiothoracic intensive care unit.
AB  - An idea involving the expansion of the role of the paediatric intensive care
      nurse and the promotion of enhanced quality patient care is presented. A point
      prevalence study was conducted to investigate practices in weaning from
      ventilation in children after cardiac surgery. The development of a clinical
      protocol, audit of practice, education and training and implementation of a
      change in practice are discussed. Recommendations for future research are made.

PMID- 11249254
TI  - Proning patients in intensive care.
AB  - Patients with acute lung injury pose significant problems for the intensive care
      team. The use of the prone position with these patients is attracting increasing
      interest. Information on the practicalities of proning was obtained from other
      intensive care units by using a simple questionnaire. The necessity for nursing
      guidelines for proning is discussed, and the consequent development of these is
      described.

PMID- 11249255
TI  - Management of patients with chronic obstructive pulmonary disease in ICU and
      promotion of smoking cessation.
AB  - Chronic obstructive pulmonary disease (COPD) is an increasingly significant
      health problem. Pathophysiological effects of smoking are outlined in this paper.
      Management of patients with COPD in ICU is discussed. Treatment options available
      to treat COPD patients are described. Health promotion and aids available to
      assist cessation of smoking are discussed.

PMID- 11249256
TI  - Continuous positive airway pressure (CPAP) in the intensive care unit--uses and
      implications for nursing management.
AB  - CPAP therapy has several clinical uses and offers the potential for numerous
      benefits to selected patients. Extensive literature is available on medical
      application of CPAP, but very little can be found on the nursing implications.
      There exists a potential to increase the nurse's role in the assessment,
      application, management and evaluation of CPAP therapy. Established psychological
      implications of CPAP therapy exist. Research is required to investigate and
      develop the nursing role with regard to CPAP therapy.

PMID- 11249257
TI  - Clinical supervision: a challenge for critical care nurses.
AB  - Clinical supervision is defined and its implementation nationally is charted.
      Recognised models and choosing the appropriate model for implementing clinical
      supervision are discussed. A description of the initiatives undertaken with
      regard to clinical supervision within Southend Hospital is included, with
      particular reference to the Adult Intensive Therapy Unit; possible ways forward
      are identified. Quantitative data, obtained through a pilot questionnaire, from
      identifiable intensive therapy units across the North Thames and Eastern Region,
      are analysed.

PMID- 11249258
TI  - Addressing sexuality in intensive care: an addition to the curriculum.
AB  - A range of views of sexuality is explored, concluding that sexuality is more than
      sexual orientation. A review of the literature revealed that little attention is
      given by nurses in intensive care to meeting those needs of patients which relate
      to their sexuality. Vignettes, taken from practice, are given as examples of
      where the sexuality of a patient has been a significant element and these are
      used to examine nurses' attitudes to sexuality. An evaluation of two teaching
      sessions is given.

PMID- 11249259
TI  - Calorie use and obesity among diabetic and non-diabetic Mvskoke Indians.
AB  - Type 2 diabetes is a major cause of death among American Indians and obesity and
      physical inactivity are modifiable risk factors in the development of type 2
      diabetes. Physical activity may have both a preventive effect and a secondary
      preventive effect of lessening insulin resistance in persons with type 2
      diabetes. Moreover, for some individuals participation in daily regimens of
      physical activity is very difficult. Culture-specific physical activity may be an
      intervention to reduce obesity and prevent diabetes-related complications.
      Therefore, the research questions for this study were: (1) What is the body fat
      percentage of diabetic and non-diabetic Mskoke Indians?, (2) How does body fat
      percentage of Mvskoke Indians compare with recommended percentages for age and
      gender?, (3) What is the caloric use of Mvskoke Indians during daily and
      traditional cultural activities of dancing and stickball?, and (4) Are there
      relationships among body fat percentage, calorie use, gender, and diabetic
      status? The findings revealed that female diabetics' percentage of body fat in
      three age cohorts (40-49, 50-59, and 70+) was higher than that of non-diabetic
      females. By contrast, male diabetics had lower percentage of body fat than non
      diabetic males. The actual mean percentage of body fat of the female participants
      ranged from 38.5% to 44%, roughly twice the standard recommended percentages of
      body fat of 20-24%. No significant difference was found in calorie use by gender
      or diabetic status. Analysis of calories during traditional activities revealed
      that 30 minutes of stickball used an average of 135.7 calories. Dancing for 33
      minutes used an average of 149 calories. No significant relationship was found
      among percentage of body fat, caloric use, gender, and diabetic status.

PMID- 11249260
TI  - Systematic methods to enhance diversity knowledge gained: a proposed path to
      professional richness.
AB  - Faculty members in nursing schools have the responsibility to provide learning
      experiences for students that have the potential to solidly link indicators of
      professional richness, knowledge gained about diversity, enhanced critical
      thinking skills, ethical reasoning and decision-making. The challenge then is for
      faculty members to implement systematic methods to ensure that students are
      exposed to in- and out-of classroom experiences that result in measurable
      outcomes indicating a strong association between what a student is expected to
      learn and the diversity knowledge gained. The purpose of this study is to
      describe the effect of a target intervention derived from synthesizing multiple
      theories (social, cognitive, moral and ethical) and learning experiences on
      students' perception of global diversity. Two independent cohorts of senior
      nursing students, (control group, N = 65 and experimental group, N = 55) were
      taught a required undergraduate course: Societal Health Issues (SHI) with the
      same objectives over two consecutive years. Drastic and remarkable differences
      were demonstrated using separate multiple regression analyses of the experimental
      group (adjusted R2 change of 47% (F = 11.123, (df1 = 4; df2 = 47), p = .000) and
      control group (adjusted R2 change of 1% (F = 1.36, (df1 = 4; df2 = 52), p =
      .259). This study suggests preliminary empirical support for exploring how
      conceptual frameworks may guide faculty to consider pushing beyond traditional
      teaching methods to develop and organize systematic methods for infusing
      diversity content in courses.

PMID- 11249261
TI  - The lived experiences of adult female victims of child abuse.
AB  - The purpose of this study was to investigate the lived experiences of female
      victims of domestic violence who also identified themselves as victims of
      physical abuse as children. There have been numerous studies of identifying
      perpetrators of violence as having a history of experienced violence in the
      family of origin. However, few studies address the victims/survivors of domestic
      violence and the historical significance of abuse in the family of origin. It is
      estimated that greater than 50% of the victims of domestic violence were also
      victims of abuse as a child. The research design partially followed the
      qualitative ethnonursing methodology. This pilot project consisted of seven
      females between the ages of 37 and 58. These women were members of a long
      standing support group for battered women. The Pitts-Williams Inventory was used
      to obtain data. The instrument contained six major research questions, with sub
      questions. Data analysis was done by identifying major themes that emerged. Eight
      themes were identified. The majority of the women identified their mother as the
      perpetrator. They described a continuous cluster of violence, which included
      several different forms of violence being used consistently in order to maintain
      control and foster isolations. This type of violence continued in throughout
      their childhood and adult life.

PMID- 11249262
TI  - Health technology assessment in Alberta should registered nurses pay attention?

PMID- 11249263
TI  - Ethics in the workplace.

PMID- 11249264
TI  - The Braden Scale: is your patient at risk for pressure ulcers?

PMID- 11249265
TI  - Northern nurses of Atikameg.

PMID- 11249266
TI  - The relationship between nurse staffing in nursing homes and quality indicators.

PMID- 11249267
TI  - Predictors of early hospital readmissions of older adults who are functionally
      impaired.
AB  - When older adults who are chronically ill are discharged home, they face a high
      risk of hospital readmission. The purpose of the study was to determine whether
      low social support, low satisfaction with social support, high depressive
      symptomatology of the caregiver, and minimal use of home health care predicted
      hospital readmissions of the older adult. Sixty family caregivers were
      interviewed in their homes soon after hospital discharge and 3 months later.
      Tangible forms of social support and helping others were negatively related to
      the number of hospital readmissions. Nurses need to encourage families to seek
      and use social support that is offered.

PMID- 11249268
TI  - Pressure ulcer risk assessment in long-term care nursing.
AB  - The intent of this study was to determine whether the typical practice of using
      risk assessment tools in combination with the federally mandated Minimum Data Set
      (MDS) actually predict more cases of pressure ulcers (PUs) in long-term care
      facilities. Data in this study were collected from 555 resident charts in a
      sample of eight nursing homes. A total of 66 PUs were identified between
      September 1, 1996 and September 1, 1997 in a comparative test of the predictive
      abilities of the MDS versus the Braden Scale (BS) patient profiles. As shown by a
      Chi square test, the MDS and the BS assessment tools were valid in finding
      factors that placed residents in jeopardy of developing pressure ulcers: MDS chi
      2 = 43.68, df = 1, p < .0001 and BS chi 2 = 52.47, df = 1, p < .001. However, a
      two-tailed t test, indicated results of the BS were significantly different than
      the MDS: t = 3.77, df = 97, p < .003 and BS = t = 3.77, df = 97, p < .001. Both
      the MDS and the BS identified patient factors: the MDS identified 311 at risk,
      resulting in accurate prediction of 62 of 66 PUs, while the BS found 172 at risk
      and predicted only 46 PUs accurately. Therefore, data indicate the BS did not
      make a significant difference in predicting the incidence of pressure ulcers in
      this sample of long-term care facilities. These unexpected findings would argue
      in favor of discontinuing the practice of using the BS for PU risk assessment
      simultaneously with the MDS, but rather at independent time frames such as
      immediately upon resident admission. This would continue to support the
      recommendations of the National Pressure Ulcer Advisory Panel (NPUAP), and at the
      same time, provide a more timely pressure ulcer risk assessment.

PMID- 11249269
TI  - Caregiver burden. Instruments, challenges, and nursing implications for
      individuals with Alzheimer's disease and their caregivers.

PMID- 11249270
TI  - Prompted voiding protocol for individuals with urinary incontinence.

PMID- 11249271
TI  - Advocates for Aunt Alice.

PMID- 11249272
TI  - Strategic planning: a portfolio for care delivery redesign.

PMID- 11249273
TI  - Community care partnership: planning with the community.
AB  - We are at the threshold of transitioning from an illness delivery system to a
      health delivery system. "Partnerships for Health in the New Millennium," kicked
      off in January 2000 by Donna E. Shalala, Secretary of Health and Human Services,
      and Surgeon General David Satcher, launching "Healthy People 2010," have provided
      us with the prevention agenda for our nation. The leadership challenge ahead for
      us in the communities where we live and work is to develop a shared vision of
      health with our community partners which is committed to eliminating disparities
      in health for all our populations.

PMID- 11249274
TI  - Decisions and outcomes.

PMID- 11249275
TI  - A nurse leader's guide to writing business plans.

PMID- 11249276
TI  - Lease financing of capital acquisitions.

PMID- 11249277
TI  - The importance of planning.

PMID- 11249278
TI  - Strategic planning: myth or reality.
AB  - The reality of strategic planning often falls prey to the unplanned external or
      internal forces at work in health care. A strategic plan may sit on the shelf as
      though it were an end unto itself. This article discusses what might need to
      happen differently to change the outcome of planning generally and describes some
      of the strengths and weaknesses of planning at the system level.

PMID- 11249279
TI  - A strategic endeavor in business planning--an oncology perspective.
AB  - Planning is imperative to provide direction for future growth. The purpose of
      writing a business plan is to cultivate, analyze, and refine ideas. Planning for
      academic health centers has become increasingly important because of the changes
      in financing and delivery of health care. Gathering data related to the current
      patients population as well as the projected future trends is necessary to
      establish a framework. Identifying the market and financial data and formulating
      the strategies needed to move forward are key elements of a business plan. The
      ultimate outcome of the process is to convince others that the vision is
      achievable and to ensure allocation of resources to carry out the plan.

PMID- 11249280
TI  - Planning documents: a business planning strategy.
AB  - Strategic planning and business plan development are essential nursing management
      skills in today's competitive, fast paced, continually changing health care
      environment. Even in times of great uncertainty, nurse managers need to plan and
      forecast for the future. A well-written business plan allows nurse managers to
      communicate their expertise and proactively contribute to the programmatic
      decisions and changes occurring within their patient population or service area.
      This article presents the use of planning documents as a practical, strategic
      business planning strategy. Although the model addresses orthopedic services
      specifically, nurse managers can gain an understanding and working knowledge of
      planning concepts that can be applied to all patient populations.

PMID- 11249281
TI  - Development of a business plan for women's health services, using Malcolm
      Baldrige Performance Excellence Criteria.
AB  - A new process for business planning at Hartford Hospital was needed to achieve
      critical business results. This article describes the Hospital's use of the
      Malcolm Baldrige Performance Excellence Criteria as a way to standardize and
      improve business planning. Women's Health Services is one of Hartford Hospital's
      "centers for excellence" and one of the first to use these criteria to improve
      its service. Staff learned how to build their business plan upon a set of core
      values and concepts such as customer-driven quality, leadership that sets high
      expectations, continuous improvement and learning, valuing employees, faster
      response to market demands, management by fact, and a long-range view of the
      future.

PMID- 11249282
TI  - Planning quality patient care in today's marketplace.
AB  - New skills and perspectives are essential for nursing to meet the demands of
      shrinking resources without co-opting professional standards. Planning patient
      care in a definitive, value-based framework that ensures a balance among cost,
      work time, and quality outcomes for the consumer is the new work of nursing.
      Translating current practice into a value-based model requires an orientation to
      the content of our care, the context in which it is provided, and the
      effectiveness of our collaborative skills.

PMID- 11249283
TI  - Creating a learning environment for tomorrow's health care workforce.
AB  - The complexity of today's health care environment requires new teaching-learning
      strategies. Inova Health System's creative approach is highlighted through the
      development of the inova Learning Network.

PMID- 11249284
TI  - Building a vision for the future: strategic planning in a shared governance
      nursing organization.
AB  - Today's health care delivery environment is marked by extreme turbulence and ever
      increasing complexity. Now, more than ever, an organization's strategic plan must
      do more than outline a business plan. Rather, the strategic plan is a fundamental
      tool for building and sustaining an organizational vision for the future. The
      strong, dynamic strategic plan (1) represents a long-range vision for improving
      organizational performance, (2) provides a model for planning and implementing
      structures and processes for the management of outcomes, (3) reflects and shapes
      the organizational culture and customer focus, (4) provides decision support for
      difficult operational choices made day to day, and (5) integrates and aligns the
      work of the organization. This article describes the development, implementation,
      and evaluation of a methodology for strategic planning within a shared governance
      nursing organization. Built upon the strategic plan of the hospital, the process
      undertaken by the nursing organization reflects the following commitments: (1) to
      develop a strategic plan that is meaningful and part of daily work life at all
      levels of the nursing organization, (2) to make the plan practical and realistic
      through incremental building, (3) to locate and articulate accountability for
      each step, and (4) to build in a process for checking progress toward goal
      achievement and readjusting the plan as necessary.

PMID- 11249285
TI  - Peer visitation for the preoperative amputee patient.
AB  - The emotional adjustment to an amputation is sometimes the most challenging part.
      It is difficult for nurses and health care professionals to educate preoperative
      amputee patients because they have not shared the same experiences. Peer
      visitation of the preoperative amputee patient allows the patient to speak
      directly with another amputee who has shared a similar experience, which enables
      the patient to share feelings and concerns about the loss of a limb. This article
      will discuss the development of a peer visitation program for the preoperative
      amputee patient.

PMID- 11249286
TI  - Vascular nurse as a smoking cessation specialist.
AB  - Cigarette smoking is a leading cause of disease and preventable death in the
      United States and is a major contributing factor to the development and
      progression of peripheral arterial disease. Vascular risk decreases immediately
      after smoking cessation and within 5-10 years reaches a level almost equivalent
      to that in nonsmokers. Despite the strong emphasis on smoking cessation, relapse
      frequently occurs. Smoking relapse is affected by physiologic and psychosocial
      factors. As a smoking cessation specialist, the vascular nurse can incorporate
      pharmacologic therapies and behavioral counseling into the treatment plan for
      patients with peripheral arterial disease. The role of a smoking cessation
      specialist enables the vascular nurse to assist patients in successfully
      overcoming these factors and maintaining abstinence.

PMID- 11249287
TI  - Heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia is a rare but complex adverse drug reaction that
      can produce devastating results. Treatment and clinical management of the patient
      requires close observation and education of the pathophysiology occurring at the
      cellular level. Documented cases of heparin-induced thrombocytopenia have been
      reported in the literature for years. This case presentation details a multiple
      trauma patient in whom heparin-induced thrombocytopenia developed and the effect
      this syndrome had on her treatment and eventual recovery.

PMID- 11249288
TI  - Pulmonary emboli risk reduction.
AB  - Pulmonary embolism is a major cause of death in hospitalized patients in the
      United States. Significant morbidity is a characteristic of this phenomenon and
      its common antecedent, deep venous thrombosis. Research has shown that pulmonary
      embolism is rarely a consequence of superficial venous thrombosis. Because the
      signs and symptoms of these disorders are often nonspecific and not readily
      apparent, prevention is the goal of patient care. Nurses play a critical role in
      the prevention process. The recognition of persons at risk, the assessment of
      these patients for early signs and symptoms, and the institution of prophylactic
      measures to minimize the effect of any existing factors or to deter their
      development are essential components of nursing care. The administration of
      anticoagulation therapy, with the concomitant monitoring of its effectiveness,
      and the education of persons regarding precautions associated with the indicated
      medications and relevant lifestyle modifications are also fundamental aspects of
      care. This article provides a review of risk factors associated with pulmonary
      embolism and deep venous thrombosis, particularly prolonged immobility and
      surgery involving the abdomen or lower extremities, as well as a review of the
      respective etiologies, most notably those encompassing Vichow's triad. In
      addition, current modalities to diagnose, treat, and prevent these allied
      disorders are discussed, as well as the associated nursing management.

PMID- 11249289
TI  - The string sign.

PMID- 11249290
TI  - Common dermatoses of pregnancy.
AB  - Awareness of pregnancy-related skin changes can facilitate improved care of women
      during pregnancy by identifying those skin changes that require further
      evaluation. Women experience significant endocrine and metabolic changes during
      pregnancy that can cause both physiologic and pathologic alterations in the skin,
      nails, and hair. This review discusses the physiologic changes and pruritic
      dermatoses that are specifically associated with pregnancy. The effect of
      pregnancy on preexisting skin diseases and safe treatment options for usage
      during pregnancy will be provided.

PMID- 11249291
TI  - Promoting wound healing in the neonatal setting: process versus protocol.
AB  - The principles of wound healing have been studied and evaluated extensively in
      the animal and human adult models. Practical application has been long in coming
      to the neonatal and critical care settings. Neonatal nurses have the ability to
      significantly affect the outcome of wound healing through the care they provide
      and the approaches that they take to caring for wounds. The article reviews
      pertinent literature to provide an evidence base for optimal wound care
      activities. An outcome-oriented, functional approach to product selection is
      described to help nurses meet the goals of protection, cleansing, moist wound
      healing, and appropriate dressing and care of wounds specific to the neonatal
      population.

PMID- 11249292
TI  - Dermatologic manifestations of infectious diseases in pregnancy.
AB  - Several pathogens that have been identified as teratogenic or fetotoxic have
      associated dermatologic changes when active infection is present. Viral and
      bacterial teratogenic pathogens include herpes simplex virus 1, herpes simplex
      virus 2, varicella-zoster virus, cytomegalovirus, human papilloma virus, human
      parvovirus B19, rubella, viral hepatitis, syphilis, and gonorrhea. This article
      focuses on the characteristic dermatologic manifestation of these diseases in
      pregnancy; diagnostic strategies; interpretation of maternal and fetal laboratory
      test results; treatment of the pregnant woman, fetus, and newborn; and congenital
      outcomes of treated and untreated infection. Emphasis is placed on vaccination
      and prevention of transmission of infection to pregnant women.

PMID- 11249293
TI  - Intrahepatic cholestasis of pregnancy: a critical review.
AB  - Intrahepatic cholestasis of pregnancy (ICP) is a disease predominantly of the
      third trimester of pregnancy, characterized primarily by pruritus, biochemical
      disturbances in liver enzymes, and less frequently jaundice. Although maternal
      pruritus can be severe, overall maternal morbidity and mortality associated with
      ICP is low. However, fetal morbidity and mortality are significant with
      associated risks for meconium-stained amniotic fluid, acute onset of fetal
      compromise, spontaneous preterm labor, and intrauterine fetal demise. Current
      literature recommends obstetric management that includes frequent fetal
      surveillance with delivery when fetal lung maturity has been established.

PMID- 11249294
TI  - Abnormal cervical cytology in pregnancy: a laboratory and clinical dermatologic
      perspective.
AB  - The dermatologic examination of the pregnant woman with abnormal cervical
      cytology can be a challenge to the clinician. This article explores both the
      laboratory and clinical examinations and the special issues of each that are
      affected by pregnancy. The technique of obtaining an adequate Pap test as well as
      guidelines on managing the abnormal Pap result will be addressed. Normal and
      abnormal colposcopic findings are described with reasons why they may be more
      difficult to differentiate in pregnancy. As long as no invasive cancer is found,
      the pregnancy may proceed with continued surveillance. Postpartum regression
      rates of intraepithelial neoplasia are high.

PMID- 11249295
TI  - Neonatal skin disorders: a review of selected dermatologic abnormalities.
AB  - The skin serves many purposes, acting as a barrier to infection, protecting
      internal organs, contributing to temperature regulation, storing insulating fats,
      excreting electrolytes and water, and providing tactile sensory input. This
      article focuses on a review of normal skin structure and function and selected
      neonatal skin disorders. The disorders reviewed are Staphylococcal scalded skin
      syndrome, epidermolysis bullosa, and the ichthyoses. The basis for each skin
      disorder is presented. Nursing management and skin care are incorporated into the
      review of each selected disorder.

PMID- 11249296
TI  - Tactile stimulation and preterm infants.
AB  - A critical challenge for care providers is improving the outcomes for premature
      infants. The issues of how to control various kinds of stimulation, provide
      appropriate sensory stimulation, and maintain the quality of life of premature
      infants becomes the central focus of care given in neonatal intensive care units.
      Therefore, intervention research studies that improve the development and quality
      of life for premature infants are vitally important. This article comparatively
      analyzes and critiques five intervention studies of premature infants using
      tactile stimulation and provides future research directions in this area. By
      examining the effectiveness of the tactile stimulation studies, some evidence and
      guidance can be provided for researchers generating knowledge in this area as
      well as nurses involved in clinical care.

PMID- 11249298
TI  - Coordinated stroke care ... the next generation of stroke care.

PMID- 11249297
TI  - TPA in acute ischemic stroke. A Calgary experience.
AB  - OBJECTIVE: To examine the five key stages which comprise the essential elements
      of acute stroke care using thrombolytics. This paper will discuss the stages of
      acute stroke triage in Calgary, Alberta at the Foothills Medical Centre, Five
      primary target goals are addressed in addition to discussion of how these goals
      were met in a medical teaching centre.

PMID- 11249299
TI  - How well do proxies represent the views of cognitively impaired patients?

PMID- 11249300
TI  - Where are all the Maori nursing students?

PMID- 11249301
TI  - Making sense of qualitative research.

PMID- 11249302
TI  - Equipping nurses to care for dying children.

PMID- 11249303
TI  - Uncovering nursing education's core values.

PMID- 11249304
TI  - Putting learning into practice.

PMID- 11249305
TI  - It's all in the genes: implications for nursing education.

PMID- 11249306
TI  - Do nurses need clinical supervision?

PMID- 11249308
TI  - What it is, what it isn't.

PMID- 11249307
TI  - Developing scopes of practice for prescribers.

PMID- 11249309
TI  - Why do you do it that way?

PMID- 11249310
TI  - Tap the Internet to strengthen evidence-based oncology nursing practice.

PMID- 11249311
TI  - Electroconvulsive therapy: a review of the literature.
AB  - Electroconvulsive therapy (ECT) is a procedure that has been used in the
      treatment of mental illness for over 60 years. Despite its continued use it
      remains a controversial treatment, with questions concerning its efficacy being
      raised not only by mental health professionals, but also service users
      themselves. The following article reviews the current literature on the
      administration and effectiveness of ECT, highlighting some of the main points of
      contention in the debate over its use. In providing a balanced review of the
      literature, this article aims to serve as an information source for nurses and
      other mental health professionals who may be involved in the administration of
      ECT and care of the patients receiving treatment.

PMID- 11249312
TI  - Psychopharmacological and electroconvulsive treatment of anxiety and depression
      in the elderly.
AB  - The pharmacotherapeutics of antianxiety and antidepressant medication in the
      elderly is reviewed, and the benefits and risks of electroconvulsive therapy
      (ECT) are discussed. Physiological changes in normal ageing are described, and
      the pharmacodynamic and pharmacokinetic implications are addressed. Finally, the
      role of the advanced practice nurse (mental health/psychiatry) is discussed in
      terms of accountability, collaboration, and the development of empirical
      knowledge to enhance quality patient care.

PMID- 11249313
TI  - What can we do about acute extrapyramidal symptoms?
AB  - Antipsychotic drugs are the most effective treatment for psychotic disorders such
      as schizophrenia. However, they are known to cause a range of side-effects
      including acute extrapyramidal symptoms (EPS) that are both distressing and
      disabling. Mental health nurses play a critical role in both the detection and
      the management of these symptoms. A review of the literature was conducted to
      identify strategies for managing acute EPS. Despite a widely held belief that EPS
      are associated with noncompliance with medication, the data to support this
      hypothesis are weak. Although akathisia may negatively affect the treatment
      outcome, there was little evidence to suggest that parkinsonism or dystonia do.
      Whilst the use of anticholinergic medication may be helpful in treating acute
      parkinsonism and dystonia they were associated with their own side-effects and
      the benefit of long-term prophylactic treatment is doubtful. The literature
      suggests that logical prescribing and rapid detection and management of acute EPS
      will result in a substantial reduction in the incidence of these disabling side
      effects.

PMID- 11249314
TI  - Detecting nurse-perceived patient treatment difficulty of psychiatric patients in
      hospital: an evaluation of a patient assessment sheet.
AB  - Many changes have occurred in hospital psychiatric care, including decreased
      length of hospital stay and increased patient acuity. These changes highlight the
      need for nurses to adequately assess and formally document patient treatment
      difficulties. The purposes of this study were to determine the ability of the
      Patient Assessment Sheet (PAS) to predict patient 'problems' that psychiatric
      nurses perceived as associated with patient treatment difficulty, and to identify
      the patient problems missing from the PAS. These purposes were accomplished by
      comparing the PAS to the Hospital Treatment Rating Scale (HTRS). A correlational
      design and multiple linear regression technique were used. Eight psychiatric
      registered nurses assessed a total of 110 patients, admitted consecutively to one
      inpatient psychiatric unit. The HTRS and the PAS were used independently for each
      patient. Four PAS items (active affect, passive affect, aggression toward self,
      and patient confusion) significantly predicted 38% of the variance from the HTRS;
      and three HTRS items (isolation and withdrawal from relationships, noninvolvement
      in treatment, and wide variability in mood) significantly predicted 22% of the
      residual variance from the HTRS. The identified PAS and HTRS items help to make
      visible patient problems associated with nurse-perceived patient treatment
      difficulty. This identification is potentially important for both clinical and
      political purposes.

PMID- 11249315
TI  - The development and testing of the Mental Health Problems Perception
      Questionnaire.
AB  - This paper reports the development and psychometric testing of the Mental Health
      Problems Perception Questionnaire. This questionnaire was developed to measure
      the therapeutic commitment, role support and role competency of non-mental health
      specialist nurses (generalists) to working with patients with mental health
      problems who live in rural communities. The instrument was demonstrated to be
      valid and reliable in this population. The questionnaire was underpinned by an
      explicit theoretical model which facilitates an understanding of the factors that
      influence effective psychosocial nursing interventions with this client group.

PMID- 11249316
TI  - The development and piloting of a patient held record with adult mental health
      users.
AB  - This article reports on the development and piloting of a patient held record for
      adult mental health users. Development of the format and content of the record
      was determined in consultation with a user group. Piloting and subsequent
      evaluation of the record with users revealed a number of issues which need to be
      addressed in the promotion of a patient held record.

PMID- 11249317
TI  - The labyrinth of health as perceived by two groups of community nurses.
AB  - The purpose of this research was to examine a group of 16 health visitors and a
      group of 16 community mental health nurses perceptions of health and health
      awareness. The study was mainly qualitative and exploratory in nature with some
      quantitative data being collected to condense the data. All 32 respondents were
      interviewed using a semistructured, tape recorded format. The content of the data
      was scrutinized and emerging patterns, themes, and concepts were noted and coded
      using a tried and tested theoretical process. The findings were related to the
      questions asked and comparisons were drawn between the information received from
      each group. An examination of the data revealed that the group of health visitors
      defined health terms of 'functional' states, described health in physical terms,
      and practiced physical exercises as their health valuing behaviours in order to
      keep themselves healthy. This key theme also emerged with reference to their
      value of health at family and global levels. Taking their health for granted and
      being grateful for it when they saw someone in the community less well off than
      themselves was also highlighted as a major theme. The group of community mental
      health nurses defined their health in 'being' states and described health in a
      holistic manner. They perceived the value and concept of 'freedom' to be related
      to and embraced within the concept, definition and value of health at individual,
      family and global levels. They practiced aesthetic health valuing behaviours to
      enhance their appreciation of health and self. Mental health, the ability to make
      choices, being self actualizing and the capacity to love and be loved were the
      key themes emerging throughout this group's responses. It would be interesting to
      develop this research from a community health perspective.

PMID- 11249318
TI  - Gatekeeping access to services at the primary/secondary care interface.
AB  - This paper examines the role that mental health clinicians play in gatekeeping
      access to services at the primary/secondary care interface. Layder's research map
      is used to explore the factors that influence gatekeeping decisions at four
      interrelated levels of social organization; self, situated activity, setting and
      context, plus a historical dimension that permeates each level. The main theme
      that emerges from the analysis is that the dilemmas that arise from attempting to
      control the demand for care are difficult to resolve for policy makers, managers
      or clinicians alike. A combination of factors make it difficult to establish
      consistent priorities including: the uneven distribution of specialist services,
      the lack of a consensus definition of severe mental illness and the difficulty of
      weighing the potential benefits of care for the individual against the need to
      ensure that resources are distributed fairly. It is suggested that there are no
      easy answers to these dilemmas because gatekeeping is a socially contested
      process, in which there will be winners and losers.

PMID- 11249319
TI  - Psychiatry and citizenship: the Liverpool black mental health service users'
      perspective.
AB  - This study investigates the appropriateness of statutory psychiatric services for
      the Black community in Liverpool by appraising the services through the views of
      Black British, Black African, and Black Caribbean service users residing in
      Liverpool. Semi-structured and unstructured interviews, which characterize
      methodological approaches used to harness and deploy services users' views to
      generate involvement in service decisions at local level, are utilized and
      analyzed by thematic content analytical procedures described in Burnard (1991),
      and demonstrated by Evans (1995). Interview transcripts are individually studied,
      manipulated, and aggregated to generate the main themes discussed during this
      process. The findings are discussed in the presentation of the data as supporting
      or disconfirming evidence of the researcher's understanding of the anomalies in
      the characteristics of psychiatric services in cross-cultural settings. The study
      shows that structures already exist in the Black Community for mental health
      service providers to action user involvement, a contemporary policy initiative in
      the British National Health Service (DoH 1997). This study demonstrates the
      process.

PMID- 11249320
TI  - Finding time for patients: an exploration of nurses' time allocation in an acute
      psychiatric setting.
AB  - This article explores the proportion of work time psychiatric nurses spend in
      potentially psychotherapeutic one-to-one communication with patients. Twenty
      staff nurses from three acute admission wards in a psychiatric hospital in
      Northern Ireland were observed. The time spent in a selection of routine
      activities was recorded using a specially developed observation system Nurses'
      Daily Activity Recording System (NURDARS). The main findings were: (i) less than
      half of the working day (42.7%) was spent in patient contact, and (ii) the
      proportion of work time which was devoted to potentially psychotherapeutic
      interaction with patients was very small (6.75%). The implications and
      limitations of the study are discussed and suggestions are made for the
      management and practice of psychiatric nursing, for the education of psychiatric
      nurses, and for further research.

PMID- 11249321
TI  - Managing protest behaviour: from coercion to compassion.
AB  - The compulsory detention and involuntary treatment of mentally disordered
      offenders is fraught with conceptual difficulties relating to liberty and the
      protection of others from harm. It is often the case in forensic psychiatry that
      patients consider themselves unjustly treated and unfairly judged, which may
      result in some engaging in protest behaviour. This paper is concerned with
      setting out some philosophical positions in relation to such loss of liberty and
      forced treatment, and views the protest scenario as a form of hostage situation.
      This perspective shifts the management of protest behaviour from strategies of
      coercion to those based on negotiation. Finally, four models of management are
      set out to facilitate the understanding of protest, and these refer to: (a)
      crisis bargaining by tracking relational paradox; (b) negotiation as
      psychotherapy; (c) bio-behavioural dimension; and (d) protest as post-traumatic
      stress disorder.

PMID- 11249322
TI  - Peering through the darkness: the subjective experience of clinical depression.

PMID- 11249323
TI  - Does patient education enhance compliance with clozapine? A preliminary
      investigation.

PMID- 11249324
TI  - Quantitative measurement of service user preferences for mental health care: a
      comparison between consumer satisfaction surveys and conjoint analysis.

PMID- 11249325
TI  - Medical errors--is the system "ill?".

PMID- 11249326
TI  - A multidisciplinary renal osteoporosis clinic: a new role for the nephrology
      nurse.
AB  - Osteoporosis is one form of osteodystrophy that may be treated and/or prevented
      with a comprehensive approach. At the University of North Carolina at Chapel
      Hill, we created a multidisciplinary kidney osteoporosis clinic with a nephrology
      nurse at the center of patient care. This article will describe the development
      of our clinic, our multidisciplinary approach to patient care, and how the
      nephrology nurse is uniquely qualified for the central role in the care of these
      patients. Preliminary outcome data is described, demonstrating the positive
      effect our clinic has had on patient care. A description of the pathogenesis and
      treatment of osteoporosis in renal patients is also given to provide background
      for the reader.

PMID- 11249327
TI  - Perceived consequences of being a renal failure patient.
AB  - This study describes the perceived consequences of illness and treatment among
      end stage renal disease (ESRD) patients. A qualitative, explorative-descriptive
      design was used, which included continuous ambulatory peritoneal dialysis (CAPD)
      (n = 26), hemodialysis (HD) (n = 30), and transplantation (n = 30) patients. Data
      collection was performed using unstructured interviews, mostly in the patients'
      homes. All interviews were tape-recorded with permission from the informants,
      transcribed verbatim, and analyzed by content analysis. An overall theme was
      identified, "Wishes for independence and normality." Four main categories
      emerged: "Wish for normality," "Wish to manage one's own life," "Deprivation of
      one's normal life," and "Concerns." Interview statements were classified in 11
      subcategories: live as usual, keep up appearances, social comparison,
      hope/fulfilled dreams, freedom/lack of freedom, control/lack of control, losses,
      dependence on others, physical problems, disgusted with oneself, and broodings.
      The perceived consequences of being an ESRD patient are multidimensional and
      involve several aspects of everyday life. It is important for nurses to
      appreciate the patient's view of illness as well as the patient's perceived
      stressors and expectations. It may help to direct the focus of nursing assessment
      in planning and implementing nursing care.

PMID- 11249328
TI  - A decade review: methods to improve adherence to the treatment regimen among
      hemodialysis patients.
AB  - Hemodialysis patients are asked to adhere to a very difficult treatment regimen
      consisting of fluid and diet restrictions, many daily medications, and, usually,
      3- or 4-hour hemodialysis sessions three times each week. Many hemodialysis
      patients fail to adhere to their prescribed treatment. Although this regimen is
      difficult, it is necessary for patients to adhere to the prescribed regimen for
      optimal health and well-being. It is important for nephrology nurses to know what
      interventions help patients overcome the barriers that keep them from adhering to
      the prescribed treatment. The purpose of this paper is to review the literature
      to examine the research that has been published on methods to improve adherence
      to the treatment regimen among hemodialysis patients. Behavioral approaches,
      education, and primary nursing are interventions that have been researched. More
      research has been reported on the demographics of noncompliant hemodialysis
      patients than on effective methods that help patients improve adherence to the
      treatment regimen. Demographic characteristics do not consistently predict
      compliance for individual patients. Each patient is unique. Research supports the
      idea that the nephrology nurse should spend time with the patient on a regular
      basis in order to understand the factors that hinder the individual patient from
      adhering to the treatment regimen. The nurse who knows the patient well is
      empowered to develop individualized interventions aimed at reducing barriers that
      interfere with the patient's ability to adhere the prescribed treatment regimen.

PMID- 11249329
TI  - Hemodialysis and homelessness: a literature review and a call for research.
AB  - As the U.S. population ages, the number of persons with chronic conditions
      increases. Social isolation, declining health status, unemployment, and/or
      decreased income levels can all contribute to a forced change in residence.
      People on hemodialysis who are living in precarious housing situations are an
      under-recognized and silent population. Anecdotal evidence suggests that there is
      a larger population of hemodialysis patients living in various nontraditional
      situations than the literature reveals. This article describes both the homeless
      and chronic renal disease populations and demographic overlay, and issues a call
      for research.

PMID- 11249330
TI  - Dietary restrictions in maintenance hemodialysis: experiences of English speaking
      West Indian adults.
AB  - Dietary therapy is a critical component of the hemodialysis prescription. The
      purpose of this qualitative study was to investigate and describe the lived
      experience of dietary restrictions in English-speaking, West Indian (WI) adults
      on maintenance hemodialysis. A phenomenological approach using open-ended
      interviewing strategies was employed. The sample consisted of five patients who
      received their treatment in the chronic hemodialysis unit at an inner-city
      hospital. Following satisfaction of delimitations, each subject had a tape
      recorded interview with the researcher that was immediately transcribed by a
      medical transcriber. Qualitative methods were used to analyze and interpret all
      data from which the following themes emerged: (a) diet is a major problem; (b)
      patients adapt by trial and error; (c) WI foods are not listed in the renal
      failure diets; (d) patients believe that staff lack sufficient knowledge about WI
      diet and foods; (e) patients believe that eating an American renal diet made them
      feel worse; and (f) both staff and patients need information on WI foods. The
      current food list available to the WI hemodialysis patient is insufficient. There
      is a knowledge deficit regarding WI dietary patterns and their modification for
      patients on hemodialysis. Further collaborative research is clearly indicated.
      The findings from this study will add knowledge and understanding in caring for
      the renal failure population as their numbers continue to increase within this
      ethnic group.

PMID- 11249331
TI  - Assessing the impact of concomitant therapies on anemia in dialysis patients.
      Case study of the anemic patient.
AB  - A wide variety of prescribed and over-the-counter (OTC) agents can affect the
      production or viability of red blood cells, thereby contributing to anemia. An
      apparent hyporesponse to Epoetin alfa therapy in end-stage renal disease (ESRD)
      patients can sometimes be traced to a medication prescribed to treat a comorbid
      condition. The anemic potential of many of these agents has been defined and can
      often be anticipated or avoided by examining and modifying the regimen. Nurses
      can help assess and prevent medicine-related hyporesponse to Epoetin alfa by
      obtaining thorough histories and providing ongoing counseling on the need to
      minimize exposure to substances that contribute to anemia. A case study is
      provided to illustrate the use of nursing assessment skills to identify potential
      drug-related hyporesponse to Epoetin alfa.

PMID- 11249332
TI  - Identifying the insertion site of a central vein catheter.

PMID- 11249333
TI  - Workplace violence: "up close and personal".

PMID- 11249334
TI  - Lessons learned.

PMID- 11249335
TI  - Detrimental effects of hypothermia: a systems analysis.
AB  - Hypothermia influences body functions in many positive and negative ways.
      Hypothermia may be purposely induced during neurological or cardiac surgery for
      its cerebral protectant effects. However, hypothermia during the perioperative
      period is often detrimental, leading to increased bleeding and blood product
      utilization, as well as prolonged stays in the PACU. This article presents an
      overview of the physiology of temperature regulation and risk factors for the
      development of perioperative hypothermia. The effects of hypothermia on various
      body systems also are discussed and perioperative concerns explored.

PMID- 11249336
TI  - Effects of positive end-expiratory pressure on diaphragm function.
AB  - Patients admitted to the PACU after surgery may require mechanical ventilation.
      Knowledge about the anatomy and physiology of the diaphragm and its association
      with ventilator modes may be helpful in the management of this patient. As the
      acuity of PACU patients increase, more patients may also be on higher levels of
      positive end-expiratory pressure (PEEP), requiring PACU nurses to understand the
      relationship between PEEP and diaphragm function to facilitate weaning. This
      article provides a review of the mechanical ventilation mode of PEEP and its
      relationship to diaphragmatic performance. The physiological effects associated
      with the use of PEEP are also reviewed.

PMID- 11249337
TI  - Assessment and nursing management of hypertension in the perioperative period.
AB  - Over 50 million persons in the United States have hypertension, making it one of
      the most common abnormalities found in the perioperative patient. Often
      discovered during the preoperative assessment of the patient scheduled for
      surgery, hypertension raises many concerns in the perioperative period, including
      hemodynamic control during anesthesia, postoperative complications, and the risk
      of comorbidities that may not be evident until the patient is stressed. This
      article concentrates on the identification of hypertension preoperatively, the
      potential problems associated with hypertension in the entire perioperative
      period, and pharmacologic and nursing management.

PMID- 11249338
TI  - The nursing shortage: implications for perianesthesia nursing in the 21st
      century.
AB  - Nursing shortages are not a new problem, and in fact, seem to come around on an
      almost cyclical basis. Although nursing shortages are not unusual, this first
      shortage of the 21st century exhibits unique characteristics that could undermine
      the very fiber of nursing, and healthcare in general. Members of the ASPAN Board
      of Directors attended the Nursing Shortage: Practical Solutions Conference
      conducted by The Forum on Health Care Leadership and sponsored by Cross Country
      University (a continuing education company part of Cross Country Staffing, Boca
      Raton, FL) and Curtin Calls, held in September of 1999 (Ft Lauderdale, FL). This
      article provides an overview of information gathered at that conference and will
      also explore the challenges and opportunities that this shortage poses to the
      specialty of perianesthesia nursing.

PMID- 11249339
TI  - Are you watching the clock? Let criteria define discharge readiness.
AB  - The primary function of the perianesthesia team is to assure that physically
      stable individuals are sent home with the necessary education and preparation for
      the transition to self-care. The use of discharge criteria provides a safe and
      efficient process for this transition.

PMID- 11249340
TI  - Life safety in the perianesthesia care environment: planning for internal
      disasters.
AB  - Nurses in perianesthesia areas have a critical responsibility to provide a well
      thought-out safety plan in the event of internal disaster. Working together as a
      team, identifying key people, assigning responsibilities, and communicating the
      plan will prepare the staff to efficiently manage the unexpected event.

PMID- 11249341
TI  - Informed consent.
AB  - Patients have a right to informed consent and a right to forego treatments,
      procedures, or surgery if they feel uninformed or have changed their minds.

PMID- 11249342
TI  - The new Joint Commission Accreditation of Healthcare Organizations' requirements
      for pain assessment and treatment: a pain in the assessment?
AB  - The new Joint Commission on Accreditation of Healthcare Organizations' (JCAHO)
      requirements reflect some major revisions to several standards regarding pain
      assessment and management. This article contains a brief review of those changes
      that can be found in the 2000 Hospital Accreditation Standards in Patient Rights
      and Organization Ethics, Assessment of Patients, Care of Patients, Education,
      Continuum of Care, and Improving Organization Performance (JCAHO: CAMH Revised
      Pain Management Standards. Available at http://www.jcaho.org/standard/pmhap.html,
      pp 1-13. Accessed January 20, 2000.).

PMID- 11249343
TI  - Pediatric asthma.

PMID- 11249344
TI  - RN and LPN accountabilities and responsibilities.
AB  - Although the scopes of practice of RNs and LPNs overlap, the main difference
      between the two scopes lies in the breadth and depth of the knowledge, and the
      clinical judgments of registered nurses. Changes in staff mix and introducing
      LPNs into organizations that were previously staffed only by RNs provide
      challenges for all care providers. Moving from all RN staffing to an RN-LPN mix
      requires redefining how care is delivered. Carefully planned, with an awareness
      of the scopes of practice and of the breadth and depth of nursing knowledge of
      RNs and LPNs, these changes can be accomplished with minimal conflict and
      disruption.

PMID- 11249347
TI  - Patient care hangs in the balance.

PMID- 11249346
TI  - Why do they complain about nurses?

PMID- 11249348
TI  - Is certification the current gold standard?

PMID- 11249349
TI  - Dealing with temper tantrums ... a lesson from home.

PMID- 11249350
TI  - Ethics in practice. The case of Mr. W.

PMID- 11249351
TI  - Patient restraints. Protection for whom?
AB  - Healthcare providers often face the decision of whether to restrain a patient. If
      the patient suffers an injury based on the decision not to restrain, will the
      provider be held liable? Healthcare providers express concern about the
      legalities of using restraints to prevent patient injuries and about which
      circumstances would be considered appropriate to restrain patients. This article
      presents case law that delineates what standard of nursing care generally must be
      breached before nurses will be held liable for injury from the use or nonuse of
      restraints. Policies and guidelines for consideration by nurse executives in the
      use of patient restraints are presented.

PMID- 11249352
TI  - Childhood immunizations. Policies, problems, and remedies.
AB  - Attaining full immunization coverage, particularly for those younger than 2 years
      of age, is a critical investment in the well-being and future of this nation's
      children. Unfortunately, not all children receive this health protective
      intervention equally or on a timely basis. The measles epidemic of 1989-1991
      caused much concern to providers, parents, and government officials and focused
      the spotlight on this major healthcare issue. Those involved began to question
      the adequacy of federal immunization laws and the effectiveness of existing
      immunization programs. This article examines both significant former healthcare
      policy/legislation focused on childhood immunizations and current concerns
      regarding childhood immunizations in the United States, and offers a broad range
      of suggestions for future policy/practice modifications to address these
      concerns.

PMID- 11249353
TI  - Taking a fresh look at the national tragedy of suicide.

PMID- 11249354
TI  - Couples' perceptions of wives' CFS symptoms, symptom change, and impact on the
      marital relationship.
AB  - The purpose of this descriptive correlational study was to describe the
      differences in couples' perceptions of wives' Chronic Fatigue Syndrome (CFS)
      symptoms and to describe the relationship between changing symptoms and the
      marital relationship. The convenience sample of 131 wives with CFS and their
      spouses reported symptom changes similarly. However, wives reported significantly
      higher problem levels for constitutional, fatigue, cognition, central nervous
      system (CNS), musculoskeletal, and allergy symptom domains and significantly less
      problem levels of mood disturbance domain than their husbands. Husbands who
      reported more symptom changes also reported lower marital adjustment, less
      empathy and support from their wives, and more conflict within the relationship.
      Wives who reported more symptom changes reported lower marital adjustment, less
      empathy for their husbands, and more conflict within the relationship and had
      husbands who reported lower marital adjustment and less empathy and support by
      the wives.

PMID- 11249355
TI  - The expression and comparison of ward incident rates.
AB  - The expression of ward incident rates in past research has been unclear and
      disorganized, resulting in incomparability of information between studies and a
      lack of precision. Five methods of incident rate calculation and expression are
      named and described in this article, and their advantages and disadvantages are
      delineated. Modest recommendations are made as to how researchers should use and
      express incident rates in the study of violence, absconding, self-harm,
      seclusion, constant observation, and other such behaviors.

PMID- 11249356
TI  - Basic empathy in older adults: conceptualization, measurement, and application.
AB  - Older adults comprise the most rapidly increasing age group in America. In
      addition, an increasing number of older adults are involved in helping behaviors
      or volunteering. Although empathy has been identified as a critical component of
      a helping relationship, few studies concerning empathy have been conducted with
      older adults and few instruments have been developed that can be used with this
      population. The purpose of this study was to explore the relationship between two
      measures of empathy in older adults. The Hogan Empathy Scale and an Adjective
      Check List Empathy Scale were used to assess basic empathy in 43 older adults
      between the ages of 63 and 96. Results indicated that the mean scores of older
      adults were lower than mean scores in younger populations. Scores on both
      measures were comparable suggesting that both instruments could be used to
      measure basic empathy in older adults.

PMID- 11249357
TI  - Living with schizophrenia: the family illness experience.
AB  - Mental health nurses have the opportunity to provide parents and siblings of a
      schizophrenic family member with information, empowering them to care for
      themselves and their ill loved one. By understanding the emotional reaction
      families have to the illness and the effects of social stigma, nurses can help
      families overcome the barriers to care by establishing a supportive practice.
      This article describes schizophrenia in terms of its impact on parents and
      siblings, including novel implications for nursing practice and research.

PMID- 11249358
TI  - Mental health status in refugees: an integrative review of current research.
AB  - The purpose of this integrative review was to assess the results of current
      published quantitative research about refugees and their mental health status. An
      extensive literature review using several approaches was performed. A group of 12
      articles met inclusion criteria for this study sample (N = 12). All 12 studies
      showed negative mental health status in the refugees sampled. Mental health
      outcomes included posttraumatic stress disorder, depression, anxiety, psychosis,
      and dissociation. This review revealed a lack of culturally sensitive
      understandings and diagnostic measures in the majority of current published
      quantitative research on refugees. The scope of this research for health
      professionals is broad, as the number of refugees continues to rise.
      Recommendations for clinicians include an expanded range of practice to
      incorporate refugee-specific assessment and treatment.

PMID- 11249359
TI  - Regulating: the social control process registered nurses use to teach psychiatric
      patients about their medications.
AB  - In light of rising costs of health care, trends toward community based care, and
      greater demands by patients for control over their health, patient teaching has
      become a necessary part of the registered nurse's role. The purpose of this study
      was to describe how nurses teach patients with mental illness about their
      medication regimens. Twenty-nine nurses from three mental health settings in
      Australia participated in semistructured interviews and participant observation.
      The constant comparative method was used to analyze the data. Findings from this
      study indicated that the process of regulating, a social control process, was
      used by nurses to teach mentally ill patients about their medication regimens.
      Implications for practice and education are drawn from the findings of this
      study.

PMID- 11249360
TI  - When is a health care system not an ethical health care system? Suspending the do
      not-resuscitate order in the operating room.

PMID- 11249361
TI  - Risks and complications of peripherally and centrally inserted intravenous
      catheters.
AB  - Increased nursing vigilance is needed while caring for critically ill patients
      who have i.v. catheters. All i.v. sites should be selected based upon the i.v.
      therapy needs of the patient, using the shortest catheter and smallest size
      possible to meet the treatment needs of the patient while avoiding excessive
      repeated insertions of peripheral IVs. Meticulous handwashing, site preparation,
      and the use of sterile technique during insertion and maintenance are essential
      to minimize the risk of infection. Use multilumen catheters only when necessary
      because these catheters have an increased manipulation and associated infection
      risk. Observe for signs and symptoms of localized, systemic, mechanical, and
      metastatic (e.g., vertebral osteomyelitis and endocarditis) foci of infection.
      Additionally, remove all unnecessary or poorly performing i.v. catheters. I.v.
      sites that do not yield a blood return but will accept i.v. solutions are in the
      process of becoming occluded. Most likely, there is a fibrin sheath that is
      developing along the catheter's inner lumen and opening, decreasing the
      catheter's effectiveness. Accommodate the need to replace a catheter into the
      patient's plan of care rather than allowing the catheter to occlude and then
      replacing it under emergent or rushed conditions.

PMID- 11249362
TI  - Intraoperative disseminated intravascular coagulopathy.
AB  - Perioperative management of DIC is, at best, difficult, but it is not impossible.
      Preventing the onset of DIC is the key and is best achieved by recognizing and
      correcting predisposing factors. Nurses caring for critically injured patients
      must exercise a high index of suspicion and prepare for dealing with these risk
      factors. The development of a massive transfusion protocol assists in maintaining
      a proactive approach to managing patients in need of multiple transfusions of
      blood and blood components. Alternative approaches to surgical management might
      assist the patient by allowing the health care team to rapidly identify and
      correct any predisposing factors rather than allowing them to go unchecked,
      resulting in uncontrolled complications, such as DIC and patient death.

PMID- 11249364
TI  - Applications of indirect calorimetry.
AB  - Indirect calorimetry should be considered a useful and practical adjunctive
      technology that can assist in the assessment and management of critically ill
      patients. Examples of applications of indirect calorimetry include nutritional
      assessments of metabolic status, evaluation of the oxygen cost of breathing
      during mechanical ventilatory support, and measurement of oxygen transport for
      the purpose of evaluating patient tolerance of therapies and effectiveness of
      therapeutic interventions. Multidisciplinary teamwork can make use of this
      technology to develop greater understanding of the metabolic needs of critically
      ill patients and to test interventions that advance evidence-based clinical
      practice in the care of these vulnerable patients.

PMID- 11249363
TI  - Necrotizing fasciitis. A perioperative case study.
AB  - NF involves rapidly spreading inflammation with necrosis of superficial fascia,
      fat, and possibly muscle and epidermis. Severe systemic toxicity can be
      associated with NF and mortality rates can reach 74% with this so called flesh
      eating disease. Treatment modalities include antibiotics, surgical intervention,
      and other therapies such as hyperbaric oxygen. Successful treatment of NF can be
      facilitated with diligent nursing assessment and intervention.

PMID- 11249365
TI  - Malignant hyperthermia. Update 2000.
AB  - MH is a life-threatening crisis that can be controlled if promptly recognized and
      appropriately treated. Identification of patients at risk for MH is an ongoing
      crusade. Preparedness with needed supplies available at hand facilitates optimal
      treatment. All perioperative personnel should remain current in their knowledge
      of MH management and treatment to ensure the best possible outcome for their
      patients.

PMID- 11249366
TI  - Extracorporeal membrane oxygenation. Saving tiny lives.
AB  - Infants with CDH require a dedicated nursing team that often comes from three
      different critical care areas: neonatal ICU, the ECMO unit, and the operating
      room. The team works together to directly affect the outcome of these infants
      through their preoperative, intraoperative, and postoperative care. The
      physiologic status of the patient and the psychosocial aspects of the family unit
      are of prime concern to the nursing team involved. Controversy still surrounds
      the use of ECMO because long-term effects on its survivors are unknown. It will
      be important for members of the team that manages the infant diagnosed with CDH
      to understand the benefits and limitations of ECMO. Even with its controversial
      aspects, ECMO offers the infant with CDH an alternative when conventional therapy
      fails. The collaborative efforts of the multidisciplinary team that manages these
      neonates must continue to evaluate treatment modalities and update techniques to
      maintain quality of care for this challenging population.

PMID- 11249367
TI  - State of the science of music interventions. Critical care and perioperative
      practice.
AB  - Music therapy is an easy to administer, relatively inexpensive, noninvasive
      intervention that can reduce anxiety and pain in critical care and perioperative
      patients. Libraries of relaxing music selections need to be compiled, reflecting
      diverse musical tastes. Providing patients with the opportunity to partake in
      music therapy sessions, selecting their own music, and providing them with quiet,
      uninterrupted time to listen to the music provides patients with a sense of
      control and separation from the multiple environmental stressors they are
      experiencing. Although there is now an extensive empirical base for the
      therapeutic usefulness of music therapy, particularly with the myocardial
      infarction population, few hospitals have adopted music therapy programs. Patient
      satisfaction and outcomes clearly have improved after music therapy sessions have
      been implemented. Further study with more diverse samples with a wider variety of
      medical conditions is indicated. Most of these studies used only one or two music
      sessions. It is not known whether effectiveness of music therapy sessions
      improves with repeated exposures. Further, there are little data with respect to
      optimal time for implementation of music therapy, length of music therapy
      sessions, or types of music to use. The effects of cultural diversity have not
      been addressed. Music therapy can improve the quality of care that critical care
      and perioperative nurses deliver to their patients.

PMID- 11249369
TI  - Family stresses, strengths, and outcomes after critical injury.
AB  - Because critical injury occurs without warning, there is no time for families to
      prepare for this event. Stresses caused by critical injury vary in intensity and
      duration but certainly have the potential to create a heavy burden on family
      members. Prior family stress seems to be the salient indicator of the amount of
      assistance a family will need. The number of stresses not directly associated
      with the critical injury seems to be an important predictor of family adaptation
      outcomes. Therefore, it is important that nurses assess other stresses occurring
      in the family, not focusing solely on the stresses associated with critical
      injury. Interventions that help mobilize family strengths may be effective
      strategies for promoting family adaptation outcomes. Families using few coping
      strategies or reporting reduced resources, or both need referrals to other health
      care professionals or advanced practice nurses. Patient and family care
      conferences also may be helpful in the development of intervention plans to
      mobilize individual family strengths after critical injury.

PMID- 11249370
TI  - Thinking about moral questions.

PMID- 11249368
TI  - Effects of pediatric head trauma for children, parents, and families.
AB  - Severe pediatric head injury has negative consequences for children of all ages.
      Even mild and moderate head injury results in residual impairment for school-age
      children and adolescents. Data are needed on the effects of these less severe
      insults, especially for preschoolers. Although research on the impact of the
      child's head injury on the parent-child relationship and family functioning is
      limited, the experience is likely to be very stressful for the parent and the
      family. Indeed, family integrity may be at risk. Research is needed that examines
      the effects of a child's head injury for the parent and the family over time and
      identifies factors related to these outcomes.

PMID- 11249371
TI  - Values and dealing with change. We define ourselves by the choices we have made.

PMID- 11249372
TI  - 'I'm going home to die'.

PMID- 11249373
TI  - Keeping nursing human. Interview by Laurence Savett.

PMID- 11249374
TI  - Latex glove allergy--dilemma for health care workers. An overview.
AB  - 1. The prevalence of latex allergy in health care workers is estimated to be
      between 10% and 17%. 2. Reactions from wearing latex gloves can include irritant
      contact dermatitis, allergic contact dermatitis, and contact urticaria from latex
      proteins. 3. Individuals with a history of atopy, multiple surgeries early in
      life (particularly with bladder catheterization), or allergies to certain foods
      are considered at risk of latex allergy. 4. An early intervention protocol and
      documentation forms are offered for occupational health nurses faced with
      assessing potentially latex allergic employees.

PMID- 11249375
TI  - Research based prevention strategies. Management of latex allergy in the
      workplace.
AB  - 1. Facility-wide goals should combine primary and secondary prevention approaches
      to reduce or minimize contact and aerosolized natural rubber latex exposure for
      clients, employees, and visitors. 2. Potential immune sensitization or
      continuation of symptoms of latex allergy can be reduced by using screening
      questionnaires to recognize potential risk factors or history of latex allergy;
      documentation of a referral to a physician for diagnosis; standardization of
      facility-wide general product selection; and work environment controls by
      discriminate, appropriate, informed glove choices. 3. Discriminate glove choices
      of nonlatex, non-powedered, or low allergen/non-powdered natural rubber latex
      gloves have become the primary proactive strategy adopted by hospitals and
      clinics to create a latex minimized environment.

PMID- 11249376
TI  - Is "latex safe" possible? Using a systematic approach in occupational health.
AB  - 1. Exposure to natural rubber latex, either by contact or by inhalation, can pose
      an extreme workplace hazard for sensitive health care workers. Latex reduction
      strategies are necessary to provide a safer work environment for those who are
      sensitive, and to prevent future sensitization of healthy workers. 2. Developing
      a latex reduction plan requires a multifaceted approach. An interdisciplinary
      task force is highly recommended to achieve optimal latex reduction. 3. Educating
      staff about latex safety for both health care workers and the patient population
      is important in providing a safer work environment.

PMID- 11249377
TI  - Latex sensitivity in Washington State acute care hospitals. A needs assessment
      and survey of awareness of the issues.
AB  - Based on reports from the workers' compensation system and a sentinel health
      provider network, latex gloves may be one of the most prevalent sources of
      occupational skin disorders in Washington State's health care industry. To gather
      information to understand and address this problem, questionnaires were
      distributed to 105 acute care hospitals in Washington State. Employee health and
      infection control specialists were queried on their knowledge about latex
      allergy, the perceived extent of the problem, and the actions taken to address
      the problem. With 95 of the hospitals returning completed questionnaires (93%
      response rate), 30% reported having problems with latex allergies among employees
      in their facility, with most reporting two or fewer cases. Adequate knowledge was
      found about the causes and effects of latex allergies, but definite knowledge
      gaps existed. More than 60% of all of the hospitals surveyed had made some type
      of glove alternatives available to affected employees, 4% had designated latex
      free zones, 4% had cleaned to remove latex dust, and 7% had done nothing to
      address the issue.

PMID- 11249378
TI  - Telecommuting: Occupational health considerations for employee health and safety.
AB  - 1. Information technology has moved "work" out of a centralized location.
      Employees who telecommute pose significant challenges and considerations for the
      practice of occupational health nursing. 2. Employer and employee benefits
      associated with telecommuting are reportedly associated with high levels of job
      satisfaction. However, the occupational health and safety risks of this new work
      environment need to be fully assessed and understood. 3. The ergonomic controls
      to minimize the risk of repetitive motion injuries are the same for both office
      and home locations. Additional attention need to be paid to implementing risk
      controls for other physical hazards and psychosocial considerations, as well as
      personal safety and security issues. 4. The scope of occupational health nursing
      practice needs to remain dynamic, recognizing the impact new technologies have on
      the workplace, to continue to meet the needs of the changing workplace.

PMID- 11249380
TI  - Using the solution focused brief therapy model with bereavement groups in rural
      communities: resiliency at its best.
AB  - The major goals of bereavement groups are to help resolve the conflicts of
      separation, facilitate the completion of grief tasks, provide a social support
      system, and give permission to mourn. This article describes how the Solution
      Focused Brief Therapy (SFBT) model can be applied to bereavement groups. In
      addition, the authors' provide examples of techniques useful for setting the
      beginning foundation for bereavement group work in the rural community.

PMID- 11249379
TI  - Hospice family caregivers: an experience in coping.
AB  - The purpose of this phenomenological study was to identify coping strategies of
      rural family caregivers who were caring for an elderly relative in a home hospice
      situation. Each of the six participants were interviewed on two occasions
      exploring their caregiving experience with a focus on coping strategies.
      Colaizzi's six step phenomenological method was employed for data analysis.
      Participant caregivers specifically identified coping strategies of support,
      adaptive activities, spiritual means, and avoidance. The collected data were
      analyzed and the findings compared to related caregiving literature. Implications
      for nursing practice and future research opportunities are discussed.

PMID- 11249381
TI  - Participatory action research and hospice: a good fit.
AB  - While research has always been an important component of the hospice movement in
      this country, increasingly hospices are involved in research as a result of
      demands for outcome measures and greater accountability. In addition to the more
      traditional research strategies, hospice researchers are encouraged to use
      participatory action research (PAR) in their efforts to better understand,
      document, and evaluate services. This article describes PAR and provides an
      example of a modified usage of PAR with a hospice program serving persons with
      AIDS. Whether used primarily in the planning phase of research or in conducting
      and reporting results as well, PAR maximizes input from those who know hospice
      best-staff, volunteers, patients, and caregivers.

PMID- 11249382
TI  - Association between administrative and ownership characteristics of hospices and
      their proportion of inpatient deaths.
AB  - Hospice patients are more likely to die at home than patients involved in
      conventional medical care, but the proportion of home deaths varies between
      programs. A study of the effect of hospice administrative characteristics on
      inpatient death rates is presented. Data from hospice programs that operated in
      New York State between 1993 and 1995 were obtained from the State Health
      Department and from publications of the National Hospice Organization. Inpatient
      death rates varied significantly between different operating structures: 11% for
      hospices that were divisions of home health care agencies; 34% for hospices that
      were divisions of hospital corporations; and 20% for hospices that were
      independent hospice corporations. This difference was explained by the presence
      of dedicated inpatient hospice units: Programs with such units demonstrated
      higher inpatient death rates than those without (42% versus 11%; P < .00001).
      Though not necessarily causal, these associations should be of interest to
      patients, physicians, families, and policy-makers.

PMID- 11249383
TI  - Alternative resources.

PMID- 11249384
TI  - Folic acid awareness. Targeting the college population.

PMID- 11249385
TI  - Seeking coverage for infertility. Insurers should offer reasonable services to
      help couples achieve pregnancy.
AB  - One of every eight U.S. couples will seek treatment for infertility at some point
      in the child-bearing years. Infertility affects both men and women of every
      racial, religious, ethnic, and socioeconomic group. For most of these couples,
      access to infertility treatment will be denied either because they don't have
      medical insurance, or because the coverage that they have severely limits
      infertility coverage.

PMID- 11249386
TI  - Healthy people 2010. Examining a decade of maternal & infant health.

PMID- 11249387
TI  - Fetal heart rate auscultation. Comparing auscultation to electronic fetal
      monitoring.

PMID- 11249388
TI  - Breastfeeding and oral contraceptives. Exploring opinions on the options.

PMID- 11249389
TI  - Striving for cultural competence. Providing care for the changing face of the
      U.S.

PMID- 11249390
TI  - Screening for cervical cancer. It's time to check your Pap technique.

PMID- 11249391
TI  - New PMS guidelines released. Recommendations focus on diagnosis and treatment.
AB  - To help guide health care practitioners in the diagnosis and treatment of
      premenstrual syndrome (PMS), the American College of Obstetricians and
      Gynecologists (ACOG) is releasing a revised practice bulletin on the health
      complication. The new document addresses the prevalence of PMS and recommended
      treatment options, based on a review of the scientific evidence and expert
      consensus.

PMID- 11249392
TI  - Honoring childbirth. Birth as a healing experience.

PMID- 11249393
TI  - The political process.

PMID- 11249394
TI  - Lukeman: a computerised domiciliary-client management system.

PMID- 11249395
TI  - The carers of hospital in the home patients focus on clinical processes,
      procedures and the prediction of deterioration.
AB  - The aim of this study was to explore the psychological processes and information
      needs in a group of 78 Hospital-in-the-Home (HITH) carers, randomly selected from
      two university teaching hospital HITH programs in Melbourne. Semi-structured
      interviews were conducted and explored with a computerised lexical thematic
      content analysis program. The results revealed that psychological themes of
      carers were mainly related to HITH clinical processes, procedures and the
      prediction of complications or deterioration of the patient. Carers indicated
      that they needed further information on the patients' clinical conditions,
      emergency procedures and how to detect deterioration. The implication for HITH
      nurses is that information provided to HITH carers should at least include these
      topics. The information needs of HITH carers appear to be different to those of
      the carers of individuals with chronic illness, consequently, nurses need to
      develop very specific patient and carer information materials for the HITH
      setting.

PMID- 11249396
TI  - The perceptions of rural nurses towards role change within the context of
      organisational change.
AB  - This paper, derived from The role and function of the rural nurse in Australia
      study, describes the effects of organisational change upon the rural nurses
      participating in the study. It appears that whilst change is an inevitable and
      regular feature of rural health service delivery, it does not necessarily benefit
      rural nurses or communities for reasons unique to rural life. Nurses in the study
      responded positively to organisational change when it was congruent with the
      rural norms of community consultation and collaboration, or when it ensured the
      long-term viability of the health service. They responded negatively to
      organisational change that caused role overload, role conflict or role
      insecurity, particularly when they perceived they had little control over the
      change process. This paper emphasises the need for nurses to actively participate
      in the change processes affecting their livelihood and their communities.

PMID- 11249398
TI  - Developing and testing a self medication protocol in the acute environment.
AB  - This study aimed to develop and test strategies, and demonstrate the feasibility
      and desirability of a self-medication program in an acute care hospital setting.
      Ten patients admitted with an acute exacerbation of their asthma were recruited
      to test the protocol. Although the use of the protocol was more time-consuming
      than the previous nurse administered process, patients and staff found it
      worthwhile. The outcome of the study is a protocol that could be used with a
      larger sample of patients, in the acute environment.

PMID- 11249397
TI  - Models of nursing care: a comparative study of patient satisfaction on two
      orthopaedic wards in Brisbane.
AB  - Patient satisfaction measures assist nurses in the evaluation of effectiveness of
      nursing practice and assist the process of improvement regarding established
      practice. A comparative study was carried out on 36 patients from a ward using
      team nursing (Model 1) and 38 patients from a ward using patient allocation
      (Model 2) in two orthopaedic wards of a 900 bed teaching hospital in Brisbane,
      Australia. The purpose of the research was to measure if differences in the
      levels of patient satisfaction were evident. The Patient Satisfaction Survey
      (Greenhill and Henderson 1997) used in this study encompassed aspects such as
      patients' feelings and perceptions; nurses' skills, behaviour and attitudes;
      nurses' communication and education skills; and continuity of care experienced.
      The results indicated that there were no differences between models of nursing
      care and levels of patient satisfaction. However, there were significant
      relationships between patient satisfaction and patients' characteristics such as
      age, education and health status.

PMID- 11249399
TI  - Back to the future or forward to the past? The rise of ambulatory and acute home
      care nursing.

PMID- 11249400
TI  - Chemotherapy standards for hospital in the home: how useful?
AB  - The process of developing practice standards is complex and resource intensive.
      The aim is to produce standards that meet the practicalities of clinical
      practice, are meaningful and achievable and that enhance the quality of patient
      care. This article details the process of developing chemotherapy standards for
      Hospital in the Home (HITH) and describes the results of a pilot project and the
      implications for nursing practice in this relatively new area of care delivery.
      Five Melbourne metropolitan Hospital in the Home (HITH) programs participated in
      the pilot process and evaluated the standards against their own programs. There
      was a wide variation in the skill sets nurses required depending on the structure
      of the HITH program. There were differences between programs in the nature of the
      interventions provided at home, documentation of treatments and points of contact
      for patients out of hours. Areas of concern identified by staff in the
      participating programs included the level of detail the standards required for
      assessment of the patients' home as an appropriate site to administer
      chemotherapy and the qualifications required by staff managing HITH chemotherapy
      patients.

PMID- 11249401
TI  - Rural mental health: neither romanticism nor despair.
AB  - This paper explores the relationship between rural places and mental health. It
      begins with a definition of mental health and an outline of the data that have
      led to the current concern with promoting positive mental health. We then
      consider aspects of rural life and place that contribute to positive mental
      health or increase the likelihood of mental health problems. Issues identified
      include environment, place, gender identity, violence and dispossession and the
      influence of the effects of structural changes in rural communities. The paper
      concludes with a discussion of some of the determinants of resilience in rural
      places, including social connectedness, valuing diversity and economic
      participation.

PMID- 11249402
TI  - How definition of mental health problems can influence help seeking in rural and
      remote communities.
AB  - The present study sought to understand the rural and remote influences on
      people's identification of, and response to, mental health problems. Twenty-two
      key informants living in northern and western South Australia were interviewed.
      They included mental health and generalist health professionals, other human
      service workers and mental health consumers. Three themes are reported here:
      reluctance to acknowledge mental health problems and the avoidance of appropriate
      help; stigma and the avoidance of mental health services; and the influence of
      rural and remote circumstances. Most informants considered that many mental
      health problems were amenable to help from generalist workers, with backup
      support from mental health specialists. Informants thought this intervention to
      be appropriate because a common view of mental health problems as 'insanity' and
      a culture of self-reliance created a reluctance to seek help from a mental health
      specialist. These themes need to be taken into account when designing mental
      health interventions for rural and remote communities.

PMID- 11249403
TI  - Gender roles and geographic location as predictors of emotional distress in
      Australian women.
AB  - This paper examines the emotional distress of women in urban, rural and remote
      areas of Queensland. A randomised telephone survey of 394 women found that
      geographical location was not significantly related to perceptions of life
      quality or distress. Contrary to expectation, urbanisation and isolation were not
      significant predictors of mental health and factors other than geographical
      location appear more influential in determining people's emotional wellbeing. One
      such factor, the gender role that women perceive themselves as fulfilling, was
      examined in this study and found to be significantly related to emotional
      distress. Women who saw their role as being submissive, dependent, gentle and
      timid reported significantly higher rates of distress and women perceiving
      themselves as bossy, rude and superior reported higher stress, irrespective of
      where they lived. Scores for the positive gender role of being sensitive,
      emotional and responsible grew significantly higher as the respondents became
      more rural/remote. Conversely, scores in the bossy, rude and superior domain were
      significantly higher in urban areas. This paper discusses the limitations of
      health research using global urban/rural classification schemes based on size of
      town or distance from major centres. There is mounting evidence that
      geographically based classification schemes are essentially minimalist and that
      more complex grouping variables such as gender role need to be identified.

PMID- 11249404
TI  - Brief therapy for children's mental health problems: outcomes in a rural setting.
AB  - In rural areas where specialist services are not readily accessible, there are
      practical advantages to providing short courses of therapy for children's mental
      health problems. Fifty-five parents from a rural area in South Australia
      completed questionnaires before and 3 months after receiving brief, family
      oriented therapy from a child and adolescent mental health service. Clinically,
      these families were assessed as being suitable for brief therapy because the
      children had moderately severe emotional and behavioural problems and the
      families were not severely dysfunctional. The screening process sought to exclude
      more serious and complex presentations so those families were not included in the
      current study. Questionnaires measuring the severity of children's mental health
      problems (Child Behavior Checklist) and the degree of family dysfunction (Family
      Assessment Device general functioning subscale) suggested that, on average, the
      sample met these entry criteria. The follow-up evaluation after brief therapy
      found significant overall improvement in the Child Behavior Checklist scores,
      however some children continued to show substantial difficulties. Parents'
      satisfaction with therapy was related to these scores after treatment. The
      results suggest that brief therapy was appropriate for most of the families and
      that routine follow-up could help determine those who might benefit from further
      assistance.

PMID- 11249405
TI  - A primary mental health-care model for rural Australia: outcomes for doctors and
      the community.
AB  - To address the high rate of depression and suicide in rural Australia requires a
      multifaceted approach to educate the community, improve the skills of health
      workers and provide user-friendly patient counselling. The present paper
      describes a model that covers each of these aspects and details the outcomes with
      respect to the doctors and the community. Improved awareness in the community of
      mental illness and the availability of treatment, decreasing the stigma of such a
      diagnosis, and increasing the skills and reducing the isolation of doctors in
      rural areas who treat mental illness were all positive benefits from this cost
      effective way of providing mental health care in a primary setting. The adoption
      of this model in all primary care settings is advocated.

PMID- 11249406
TI  - Rural psychologists' network.
AB  - The Australian Psychological Society has established an Interest Group in Rural
      and Remote Psychology. The aims are to foster research into psychological issues
      concerning rural and remote communities and to provide a support network for
      psychologists working in rural and remote areas. Contact details regarding
      activities and membership are outlined.

PMID- 11249407
TI  - Rural and remote mental health placements for nursing students.
AB  - Clinical placements can be instrumental in encouraging nursing students to
      consider a future career in rural Australia. Twenty nursing students from a
      metropolitan university were provided with the opportunity to undertake a
      clinical placement in mental health in a rural or remote setting. The majority of
      placements were between 2 and 4 weeks in length. They took place in community
      health centres and rehabilitation centres in New South Wales and in hospital
      inpatient facilities, remote areas and community health services in the Northern
      Territory. On return from the placement, students completed an open-question pro
      forma giving their views and impressions of their experiences and contrasting
      this with clinical experience gained in urban settings. The content of the
      students' responses was analysed and presented under the following themes: scale
      relating to urban and rural differences in population; geographical and health
      facility size; staffing matters; the environment; the students' perception of the
      clients; and professional interaction. Additional material relating to remote
      area placements is presented. Questions are raised about the maintenance of
      students' interest and the development of rural careers.

PMID- 11249408
TI  - 'Infront outback' goes national.
AB  - The National Rural Health Alliance, the Toowoomba Hospital Foundation and the
      Cunningham Centre have agreed to merge the two biennial conferences for rural and
      remote health that have been running in alternate years since 1991. This means
      that in March 2001, the National Rural Health Conference will, for the first
      time, incorporate 'Infront Outback', the Australian Rural and Remote Health
      Scientific Conference. There will, therefore, be one major biennial rural heath
      conference, dealing coherently with health scientific research and policy
      development. The recommendations to governments and national bodies that result
      should be even stronger and more highly regarded than has been the case to date.

PMID- 11249409
TI  - Leisure or therapeutics? Snoezelen and the care of older persons with dementia.
AB  - Snoezelen is the registered tradename for a multisensory environment approach
      initially established for purposes of leisure or therapeutics in the special
      education arena, but now expanding into a variety of client groups and settings,
      most notably in the care of older persons. Snoezelen is making its way into
      Australia at a rapid rate despite a lack of evidence-based research. This paper
      looks at the Snoezelen phenomenon and searches the literature to review the
      history and contemporary use of this multisensory environmental work. While most
      articles indicate positive outcomes Snoezelen is not without its critics, some of
      whom focus on the lack of rigorous research while others critique the
      artificiality. As a leisure approach Snoezelen appears to add quality to the
      culture of the care environment.

PMID- 11249410
TI  - Death in the Finnish family: experiences of spousal bereavement.
AB  - In this study dimensions of grief were examined using the Hogan model for widowed
      Finns. The aspects of loss were analyzed from the answers to an open-ended
      question. The study group consisted of 242 widows and 76 widowers, whose spouse
      died more than 6 months prior to the data collection. The numerical data were
      analyzed to determine whether dimensions of grief were gender related. Content
      analysis was used when analyzing the written answers. The findings of the study
      demonstrate that there are gender differences in the expressions of grief after
      the death of a spouse. Widows expressed significantly more intense feelings of
      panic behaviour than widowers. Both widows and widowers grieved about how to
      survive after the death of their spouse. Both groups found their families and
      friends to be the most important source of support when trying to cope with their
      grief.

PMID- 11249411
TI  - The efficacy of cotton cover gowns in reducing infection in nursing neutropenic
      patients: an evidence-based study.
AB  - This pilot study aimed to investigate the routine use of cotton cover gowns in
      the care of neutropenic patients and whether the rate of infection would increase
      if they were not used. Patients were randomly placed into alternate groups on
      admission and nursed with or without gowns. The patients' rates of infection were
      noted with no significant difference in infection rates. Using evidence from a
      systematic review of the literature, cover gowns have now been removed as a
      method of protecting neutropenic patients. 'Simple' and effective hand-washing,
      together with the use of broad-spectrum antibiotics, has been shown to be
      sufficient protection for these patients.

PMID- 11249412
TI  - Patient satisfaction with nursing care in a colorectal surgical population.
AB  - This paper describes one arm of a much larger, multi-site study whose hypothesis
      was that evidence-based nursing practice is more effective than routine nursing
      care in improving patient outcomes and health gain. This arm of the study
      investigated patient satisfaction as an outcome measure for those patients
      undergoing colorectal surgery. The study's relevance for nurses is in the
      potential feedback for reviewing nursing practice and health care delivery.
      Patient satisfaction with nursing care was measured through a validated
      questionnaire, the SERVQUAL, followed by interviews with a percentage of the
      study population. The results of this arm of the study confirm the importance of
      measuring patient satisfaction through a triangulated method which investigates
      thoroughly, providing feedback for continuous quality improvement. The in-depth
      interviews provided greater insight into the results of the questionnaire,
      enabling clear feedback to nursing staff at the different sites of the study.
      Results of the questionnaire revealed age, sex and education levels of patients
      as major influences on individual perceptions of nursing care. Patients whose
      surgery resulted in stomas were also less satisfied with health-care delivery.

PMID- 11249413
TI  - Recommendations for culturally sensitive nursing care.
AB  - Australia's health care clientele reflects the diversity of this multicultural
      society. Patients and health care professionals have expectations of health care
      which may not be met to their satisfaction or needs. The perceived inadequacies
      of and increased demands on the Australian health care system are reflected in
      the literature and by active political lobbying. Thus, there is an urgent need to
      investigate how the health care system can be improved and how recommendations
      from research can be put into place. One mechanism that may provide some of the
      changes required is to use the skills, experience and qualifications of
      culturally and linguistically diverse nurses. This paper, which is based on a
      descriptive ethnographic research project, will provide insight for utilizing
      this valuable and available resource, and how nursing education curricula can be
      modified to adequately incorporate transcultural nursing practices, so that
      nurses can meet the challenges of caring for Australia's multicultural
      population.

PMID- 11249414
TI  - The lived experience of seven people treated with autologous bone
      marrow/peripheral blood stem cell transplant.
AB  - Autologous bone marrow or peripheral blood stem cell transplant are recent
      treatments to offer hope of a cure or prolonged remission for certain types of
      cancer. Current literature predominantly has either a biomedical focus or deals
      with survivorship issues. The ways in which survivors perceive this treatment
      option is important in providing nurses with a deeper insight and understanding
      with which to inform nursing practice. Using methods consistent with hermeneutic
      phenomenology, seven people who survived this treatment were invited to
      participate in sharing their stories in individual audiotaped interviews. Themes
      that emerged from their stories include changing concepts of self, the
      significance of relationships, being different from the past and temporality.

PMID- 11249415
TI  - Teaching palliative care principles to UK nursing home care assistants.
AB  - This paper describes the initiatives that led to a study day for Health Care
      Assistants in the UK, focusing on the principles and practice of palliative care
      for practitioners. Topics covered were 'What is palliative care?', 'How can you
      help patients with pain', 'Needs of the dying patient', 'I don't know what to
      say', 'Answering awkward questions', and 'Ways of relieving distressing
      symptoms'. Participants valued the study day and feedback showed that the Health
      Care Assistants, essentially assistants to qualified nursing staff with minimal
      or no training themselves, had many vocational and emotional needs that were not
      being met.

PMID- 11249416
TI  - Ephedra is linked to CNS, cardiovascular risks.

PMID- 11249417
TI  - Better options for Net searches.

PMID- 11249418
TI  - VT or SVT? You can tell at the bedside.

PMID- 11249419
TI  - Keeping COPD patients out of the ED.

PMID- 11249420
TI  - Increase your visibility!

PMID- 11249421
TI  - There's what in the wound?

PMID- 11249422
TI  - Guiding seniors.

PMID- 11249423
TI  - Monitoring patients.

PMID- 11249424
TI  - Impaired nurses: reclaiming careers.

PMID- 11249426
TI  - How to obtain a specimen from a central venous catheter.

PMID- 11249427
TI  - Measuring a wound.

PMID- 11249425
TI  - Workplace violence.

PMID- 11249428
TI  - Reviewing the basics: blood group compatibility.

PMID- 11249429
TI  - Myths & facts. ... about carbon monoxide poisoning.

PMID- 11249430
TI  - Using newer cardiac markers.

PMID- 11249431
TI  - Transfusion reaction.

PMID- 11249432
TI  - How to choose the best route for an opioid.

PMID- 11249433
TI  - All about tubes. Your guide to enteral feeding devices.

PMID- 11249434
TI  - Detecting digoxin toxicity.

PMID- 11249435
TI  - Major Mac didn't think much of "modern" nursing....

PMID- 11249436
TI  - Putting a damper on cellulitis.

PMID- 11249438
TI  - ABCs: what do these initials mean?

PMID- 11249437
TI  - Tips and tricks for pediatric i.v. insertion.

PMID- 11249439
TI  - Do you have delegation savvy?

PMID- 11249440
TI  - Don't go from mad to worse.

PMID- 11249441
TI  - Preventing sharps injuries in the home.

PMID- 11249442
TI  - As real as it gets.

PMID- 11249443
TI  - Fluoxetine and hepatitis.

PMID- 11249444
TI  - Nursing models.

PMID- 11249445
TI  - "My name is Daniel".

PMID- 11249446
TI  - Resuscitation in palliative care.

PMID- 11249447
TI  - Exploring rehabilitation within lymphoedema management.
AB  - A review of the literature reveals rehabilitation to be a complex concept.
      Rehabilitation is more than a global term used to encompass the different types
      of therapy employed to reduce the effects of disability or chronic illness; it is
      a philosophical approach which provides a framework for care. This framework
      promotes an environment in which the individual is enabled to attain his/her own
      ideal of health. The concept of rehabilitation is explored within the mainstream
      management of lymphoedema to identify implications for improving practice. Areas
      in which lymphoedema therapists could strive to achieve a more rehabilitative
      approach to care include: implementing an organized and standardized approach to
      lymphoedema management, improving interdisciplinary working, developing the
      holistic scope of care, and acknowledging the central importance of the patient
      and family in clinical practice. Adopting a rehabilitative approach to
      lymphoedema management will help to promote greater patient satisfaction with
      treatment.

PMID- 11249448
TI  - Death in homes: bereavement needs of residents, relatives and staff.
AB  - This article reports findings from a study in the UK, which investigated the case
      for applying the principles and practices of palliative care to caring for older
      people dying in residential and nursing homes. It focuses on the emotional and
      practical consequences of a death occurring in these settings. It outlines the
      bereavement needs of residents, relatives and staff as well as obstacles to
      providing adequate support. Homes differed in policies and practices in relation
      to providing bereavement support for relatives. Most managers felt some
      responsibility for relatives of deceased residents, but rarely felt capable of
      providing what they perceived as appropriate bereavement support. They recognized
      the need for practical as well as emotional support for staff and other residents
      after a death but felt that they lacked the skills and time to provide this.
      Certain types of home prioritized bereavement support, but many homes operated
      under considerable resource and staffing constraints. Even where support needs
      were recognized it was often difficult to put the requisite help into operation.
      This study identified a lack of training in communication skills and in
      particular little access to training in bereavement care. This area needs to be
      addressed if residents, relatives and home staff in these settings are to have
      their bereavement needs met.

PMID- 11249449
TI  - Dying at home: evaluation of a hospice rapid-response service.
AB  - Various studies suggest that there is a preference among patients, professionals
      and the public for death to occur at home (Dunlop et al, 1989; Townsend et al,
      1990; Hinton, 1994). Data indicates that some patients are denied the opportunity
      to exercise choice in the place of death. In areas where palliative rapid
      response teams have been available more people have been able to die at home.
      This article presents the findings of an evaluation of a hospice rapid-response
      service in the Highlands of Scotland, which was designed to respond to the needs
      of people in crisis facing death. The study was designed to produce a rigorous
      and comprehensive description of a newly-operational service at the pilot stage.
      It reflects not only the views of the professionals involved but also focuses on
      the views of informal carers. Seventeen patients were referred to the rapid
      response service in its first year of operation between April 1998 and March
      1999. The service has shown some success in enabling patients to die at home and
      satisfaction with the service is high among professionals and lay carers.

PMID- 11249450
TI  - Development of a new approach to palliative care documentation.
AB  - Efficient, comprehensive documentation is a vital element of all healthcare
      provision. It not only provides a record of care, but should reflect the quality
      of that care, enable continuity of care between practitioners and reinforce care
      standards. However, documentation in palliative care often falls short of these
      ideals. This article describes the formulation of an integrated system of
      documentation which aims to address the failings of documentation procedures in
      one hospice/palliative care unit. The resulting system seeks to embody the
      rationale of palliative care within a dynamic, patient-centred approach to
      nursing documentation.

PMID- 11249451
TI  - Mini-Mental State Questionnaire: problems with its use in palliative care.
AB  - The Mini-Mental State Questionnaire (MMSQ) has been established as a reliable
      research instrument and is recommended for the early detection of impaired mental
      status (Fainsinger et al, 1993). Using reflection on a clinical incident, the
      problems associated with the clinical application of the MMSQ that may outweigh
      its usefulness are identified. The patient's experience of MMSQ as routine
      cognitive monitoring can be distressing as the person experiences loss of
      cognitive ability in a visible way. This experience has a negative influence on
      the person's quality of life, which is contrary to the essential aim of
      palliative care. Research evidence suggests that the MMSQ lacks specificity (the
      ability to detect impaired mental status) because it is affected by pre-morbid
      ability and intelligence, and therefore cannot be used to assess competence in
      decision making. Further research on the meaning of losing cognitive ability in
      terminal illness and other cognitive assessment strategies is required.

PMID- 11249452
TI  - The legal aspect of living wills: a need for clarity.

PMID- 11249453
TI  - Male cancers: the great taboo.

PMID- 11249454
TI  - Grass-roots effort leads to exemption of ESRD patients from Medicaid managed care
      mandate.

PMID- 11249455
TI  - Early referral for ESRD: is everyone on the same page?

PMID- 11249456
TI  - Lessons learned. Implementing a vascular access quality improvement program. Part
      II.
AB  - Implementing a CQI program for vascular access can seem an overwhelming task. It
      encompasses many areas that are not in the nephrologists' or dialysis facilities'
      control. However, involving the right multidisciplinary team members in the
      process and aligning the goals and objectives creates an environment conducive to
      success. Ongoing communication is critical. Everyone needs to be a part of the
      change process.

PMID- 11249457
TI  - New study identifies ESRD patient education needs.

PMID- 11249458
TI  - Almost-tolerance halves cyclosporine dose.

PMID- 11249460
TI  - Back to basics. Practical approaches to treating side effects of
      immunosuppressive medications.

PMID- 11249459
TI  - "Stranger donation"--the next level of altruism?

PMID- 11249461
TI  - Differences easing on organ allocation battleground.

PMID- 11249462
TI  - Reaching for new heights.

PMID- 11249463
TI  - Project donor. One solution to the organ donation shortage.

PMID- 11249464
TI  - A survey on cyclosporine prescribing and dispensing practices.

PMID- 11249465
TI  - Anticholinergic bronchodilators in combination.
AB  - Chronic obstructive pulmonary disease (COPD), which affects approximately 14
      million Americans, is the fourth leading cause of death in the United States and
      is responsible for an estimated US$6.5 billion in direct and indirect costs per
      year [1,2]. Its usual course is a slow deterioration of lung function and
      progressive breathlessness with activities. The age-adjusted death rate for COPD
      rose 71% from 1967 to 1987, and the 10 year mortality rate is about 50%.
      Bronchodilators form one of the mainstays of therapy in COPD patients. The
      judicious use of these agents increases airflow and reduces dyspnea in patients
      with COPD. Patients often experience a reduction in symptoms and improvement in
      their quality of life. There are several classes of bronchodilators available for
      the treatment of COPD, each with specific clinical benefits: anticholinergics,
      short-acting beta 2 agonists, combination anticholinergic and short-acting beta 2
      agonist, long-acting beta 2 agonists and methylxanthines. This chapter reviews
      the use of an anticholinergic (ipratropium bromide) concomitantly with other
      bronchodilators, focusing on patients with COPD.

PMID- 11249466
TI  - Paediatric issues relating to the pharmacotherapy of allergic rhinitis.
AB  - The prevalence of allergic rhinitis in children has risen significantly over the
      last two decades. Important comorbidities like asthma have grown in parallel due
      to a complex mix of environmental and genetic factors. These conditions have
      similar allergic inflammatory mechanisms, which raises the possibility of
      treating both conditions by targeting shared inflammatory mediators
      pharmacologically. The first line treatment for paediatric allergic rhinitis is a
      topical nasal corticosteroid or a non-sedating antihistamine. Available
      intranasal corticosteroids show superior symptom control to second-generation
      antihistamines. However, most topical steroids and non-sedating antihistamines
      have equivalent clinical efficacy within their respective classes, so the choice
      of agent depends on safety and tolerability. Ideally, topical nasal steroids
      should exhibit high local receptor binding affinity and low systemic
      bioavailability, allied with a lack of long-term growth suppression in children
      and adolescents. Regular use of topical steroids is advisable, but intermittent
      and prophylactic use is also effective. Second-generation antihistamines are
      effective and some have no adverse cardiac or sedative effects. Non-sedating
      antihistamine treatment can ameliorate rhinitis-induced decrements in learning.
      alpha-Adrenergic nasal decongestants provide short-term benefit, but topical
      agents can cause rebound symptoms. Prophylactic treatment with chromones is safe
      and effective, but multiple daily dosing is needed. Ipratroprium bromide nasal
      spray is useful as an intermittent therapy for mild disease or as add-on
      treatment, but its effect is limited to the control of rhinorrhoea. Children with
      allergic rhinitis should receive pharmacotherapy if allergen avoidance measures
      are ineffective, ideally with a topical intranasal steroid or a second-generation
      antihistamine.

PMID- 11249467
TI  - Current treatment practice in immunosuppression.
AB  - New drugs have recently been added that may eventually replace the two-decade
      dominance of cyclosporin in solid organ transplantation. This cornerstone of
      immunosuppression was introduced by Borel [1] and Calne [2] in the mid-70s. In
      1989, Starzl et al., after 2 years of preclinical experimentation, introduced
      tacrolimus (originally designated as FK506 by the Fujisawa Pharmaceutical Company
      of Japan) as a potent immunosuppressant for liver transplants [3]. Also, in
      recent years, a variety of novel purine and pyrimidine biosynthesis inhibitors
      have been tested for transplantation therapy. The leading agent which appears to
      be replacing the 35-year position occupied by azathioprine is the semi-synthetic
      morpholinoethyl ester of mycophenolic acid (MPA), mycophenolate mofetil (MMF),
      introduced by Allison [4] and Sollinger [5], and developed by the Syntex
      Corporation (now Roche Pharmaceuticals). Others, affecting different intra- or
      intercellular messages amplifying immunity, are in the pipeline.

PMID- 11249468
TI  - Dual protease inhibitor therapy in the management of the HIV-1.
AB  - Throughout the first 20 years of the HIV-1 epidemic, there have been tremendous
      advances in the development of antiretroviral therapy (ART). In 1995, the
      availability of protease inhibitors (PI) as part of triple drug regimens resulted
      in durable viral suppression with an associated decline in HIV-1-related
      morbidity and mortality. Despite this early success, limitations of therapy have
      become apparent. In particular, the need for highly potent antiviral regimens,
      the importance of outstanding adherence to therapy, drug-related toxicity and the
      increasing problem of drug-drug and drug-food interactions. Dual PI therapy has
      been investigated with the hope of overcoming these problems. Select PI
      combinations may result in synergistic antiviral activity with enhanced viral
      suppression. Moreover, the ability of select agents to inhibit the cytochrome
      P450 (CYP450) system results in pharmacologic enhancement that allows for dosing
      with fewer pills on a less frequent basis, both of which can enhance drug
      adherence. Furthermore, these pharmacologic interactions can overcome drug-drug
      and drug-food interactions. Finally, the ability to increase drug levels using
      certain PI combinations may allow for drug concentrations to exceed those needed
      to inhibit resistant strains of HIV-1. The rationale for using dual PI therapy,
      along with the results of clinical trials using various PI combinations in
      treatment-naive and experienced patients, is reviewed in this article.

PMID- 11249469
TI  - Changing therapeutic paradigms in CMV retinitis in AIDS.
AB  - Cytomegalovirus (CMV) retinitis is a common ocular complication of
      immunosuppression. The management of CMV retinitis has been continuously evolving
      over the last decade. The mainstay of therapy remains ganciclovir and foscarnet.
      However, increasing resistance and ongoing toxicities to these agents remain a
      challenge. Additional frequently utilised agents include cidofovir and
      fomivirsen. The advent of highly active antiretroviral therapy (HAART) has
      allowed the restoration of immunocompetency to many patients previously
      challenged by CMV infection. In some circumstances, HAART has even eliminated the
      need for ongoing antiviral therapy. This paper reviews the current treatment
      modalities, including their toxicities and dosing recommendations.

PMID- 11249471
TI  - Treatment of depression in comorbid medical illness.
AB  - The rate of comorbid depression and medical illness varies from 10 to 40%. Over
      the years, there has been a paucity of studies completed despite the importance
      of knowing which antidepressants are the most effective and safest to use in
      comorbid states. In this review, focus is placed on disorders in these important
      areas: cardiovascular disease, neurological disorders, diabetes mellitus and
      cancer. Cardiovascular disease complications can be related in many cases to
      platelet clumping produced by medications; reductions in morbidity can be
      achieved by reducing platelet adhesiveness. Specific results have shown
      sertraline administration to be safe in the post myocardial infarction (MI)
      state. This is a time of depression-induced increases of 200-300% in mortality.
      Evidence for safe administration of bupropion, as well as the selective serotonin
      re-uptake inhibitors (SSRIs) fluoxetine and paroxetine, is also available. The
      appearance of major depression and diabetes mellitus has been successfully
      treated with fluoxetine, sertraline and nortriptyline (NTI), however, NTI may
      lead to a worsening of glucose indices due to its noradrenergic specificity.
      Regarding neurologic disorders, there is controlled data showing the safety and
      efficacy of citalopram, sertraline and fluoxetine in post stroke depression.
      Parkinson's disease has been associated frequently with depression, as might be
      expected from its characteristic dopamine deficient state. For perhaps the same
      reason, the agents that can block re-uptake of dopamine i.e., tricyclic
      antidepressants (TCAs), have been effective in comorborbid depression with
      Parkinson's disease. In dementia, there is a paucity of information on new
      agents. However, double-blind data seems to show efficacy for sertraline,
      paroxetine and citalopram. There are few studies of cancer-related depression
      treated in a controlled fashion with antidepressants; imipramine, amitriptyline,
      fluoxetine, paroxetine, mirtazapine and mianserin (not available in the USA) all
      have support from some published studies.

PMID- 11249470
TI  - Role of aprotinin in the management of patients during and after cardiac surgery.
AB  - Management of patients undergoing cardiac surgery has evolved in recent years as
      more is understood about the physiological changes and responses that occur
      during and after cardiopulmonary bypass (CPB). In particular, our understanding
      of the mechanisms involved in haemostasis and in the inflammatory response to
      bypass surgery, has allowed significant refinements in patient management.
      Improvements in the pharmacological conservation of blood loss have been
      striking, particularly with the development of the serine protease inhibitor,
      aprotinin (Trasylol, Bayer). Aprotinin represents a significant improvement,
      especially for patients at high risk, since it reduces the need for allogeneic
      and (sometimes scarce) blood products. However, in view of its cost, making an
      appropriate selection of patients most at risk of serious blood loss is a major
      consideration in the use of aprotinin. While its mechanisms of action are not
      well understood, the use of aprotinin also appears to reduce inflammatory
      response to CPB.

PMID- 11249472
TI  - Selective oestrogen receptor modulators--current and future brain and behaviour
      applications.
AB  - Selective oestrogen receptor modulators (SERMs) are compounds that act as
      oestrogen agonists on selected targets while being oestrogen antagonists on
      others. The main targets of SERMs are oestrogen agonist activity on bone
      metabolism and several functions of the cardiovascular system, as well as
      oestrogen antagonism in the breast and uterus. They are indicated for the
      treatment and/or prevention of breast and endometrial cancer, osteoporosis and
      coronary heart disease. The extensive documentation of the multiple oestrogen
      effects on the CNS, greater understanding of the mechanisms of action, and
      especially the discovery of a second oestrogen receptor with differentiated
      distribution and mechanisms, have all led the way to the possibility of specific
      CNS-targeted SERMs. The demonstration that oestrogen selectively improves
      cognition, delays the appearance of Alzheimer's dementia, improves the feeling of
      well-being, as well as the response to antidepressant medications, provides
      targeted CNS indications for SERMs. The CNS effects of the currently marketed
      SERMs are not sufficiently explored yet. However, in postmenopausal women,
      tamoxifen and raloxifene probably show the most oestrogen agonist CNS effects. In
      women of reproductive age, competition with oestrogen probably exists, resulting
      in antagonist effects. Activity in men is still mostly unknown. It is quite safe
      to predict that the recent accumulation of knowledge, combined with the large,
      thirsty anticipated market for these 'designer oestrogens', will lead to clinical
      trials of CNS-targeted SERMs in the very near future.

PMID- 11249473
TI  - Prostate-specific antigen.
AB  - Serum prostate-specific antigen (PSA) measurements are the most useful serum
      biomarker to aid in early prostate cancer detection, clinical staging and
      therapeutic monitoring. Although the optimal use of PSA testing remains
      controversial, population based studies suggest that PSA screening reduces
      prostate cancer mortality. Customizing screening protocols based on individual
      risk factors and PSA level may be a useful approach to reduce overall costs
      incurred by widespread PSA testing. Lowering PSA cut-offs (i.e., from 4.0 ng/ml
      to 2.5 ng/ml) may reduce advanced stage prostate cancer, and the use of different
      PSA derivatives and PSA forms may reduce 'unnecessary' biopsies in some men. In
      addition to prostate cancer, manipulation and benign diseases of the prostate
      falsely elevate serum PSA levels. In contemporary clinical practice, PSA testing
      plays an important role in prostate cancer diagnosis and treatment.

PMID- 11249474
TI  - Insulin action enhancers for the management of type 2 diabetes mellitus.
AB  - Type 2 diabetes mellitus is a common metabolic disorder that has become a major
      public health problem because of the long-term microvascular and macrovascular
      complications associated with it. Tight glycaemic control has been shown to
      prevent complications, but a number of studies have shown that many patients with
      Type 2 diabetes have sub-optimal control. Insulin resistance is a fundamental
      abnormality in Type 2 diabetes but there have not been drugs that are able to
      reverse this defect. Thiazolidinediones (TZD) may, therefore, represent a
      breakthrough in the management of Type 2 diabetes as it is the first class of
      oral agents for diabetes that act as an insulin action enhancer to reduce insulin
      resistance. This review will examine available data on the currently available
      TZDs and consider its place in the management of Type 2 diabetes.

PMID- 11249475
TI  - Interferon-gamma 1b: impact of new indications (idiopathic pulmonary fibrosis).
AB  - Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive disease with
      inadequate response to conventional treatment with corticosteroids and/or
      immunosuppressive agents in most patients. Interferon-gamma (IFN-gamma), an
      antifibrotic agent, has been proposed as a novel therapeutic approach. Several
      investigators have shown a relative decrease in systemic and pulmonary IFN-gamma
      activity in patients with IPF. Experimental evidence from animal and human
      studies also suggests that IFN-gamma administration may ameliorate lung fibrosis.
      Clinical experience is, however, limited to a single clinical trial that showed
      objective functional improvement in a small number of patients treated with IFN
      gamma and low-dose corticosteroids. Further research is needed to characterise
      the efficacy, safety and optimum route of administration of this agent before it
      can be recommended for use in routine clinical practice.

PMID- 11249476
TI  - Nelfinavir mesylate.
AB  - Nelfinavir is an inhibitor of the HIV-1 and HIV-2 protease, with good in vivo
      activity in HIV-infected patients. Nelfinavir is used in combination with other
      antiretroviral medications as part of a potent antiretroviral regimen. When used
      in this manner, 50-75% of patients who are naive to antiretroviral therapy have
      plasma HIV RNA levels below the limit of detection (< 400 copies) after 12 months
      of treatment. This use of nelfinavir in combination regimens is associated with
      an increase of almost 200/mm3 CD4+ lymphocytes at 12 months of therapy. Initial
      trials and clinical experience indicate that nelfinavir is equipotent to other
      potent protease inhibitors (PIs). The drug is well-tolerated, with mild diarrhoea
      being the most common side effect in 12-20% of patients. Virologic failure of
      nelfinavir is associated with genotypic and phenotypic changes that have a unique
      pattern that may retain susceptibility to other PIs. The results of small, non
      controlled trials suggest these failures can be rescued with a second protease
      based regimen. Due to the above characteristics, nelfinavir has become the most
      frequently prescribed first line PI.

PMID- 11249477
TI  - Pharmacology and clinical experience with risperidone.
AB  - Risperidone (Risperdal, Janssen Pharmaceutica) is a second generation
      antipsychotic (SGA) for the treatment of schizophrenia and other psychotic
      disorders. It is a potent antagonist of serotonin-2 (5-HT2) and dopamine-2 (D2)
      receptors in the brain. In comparison to conventional antipsychotics, risperidone
      demonstrates superior efficacy against the positive and negative symptoms of
      schizophrenia and a decreased occurrence of extrapyramidal side effects (EPS).
      Risperidone causes less weight gain than other marketed SGAs, but can increase
      prolactin levels and cause EPS in a dose-related manner. In a variety of
      pharmacoeconomic analyses, it has proven to be a cost-effective addition to the
      antipsychotic armamentarium. As the first SGA available for front line use,
      risperidone has established a new standard of care for the treatment of
      individuals with psychotic disorders.

PMID- 11249478
TI  - A review of clinical experience with the prandial glucose regulator, repaglinide,
      in the treatment of type 2 diabetes.
AB  - Repaglinide is a novel insulin secretagogue that was developed as a prandial
      glucose regulator for the treatment of people with Type 2 diabetes mellitus. It
      is used flexibly, taken prior to meals, in order to limit subsequent postprandial
      blood glucose excursions as well as the dependent basal blood glucose
      concentration. In theory, the pharmacological profile of repaglinide is well
      suited for this role. Taken at mealtimes, its relatively rapid-onset and short
      duration of action counteract a fundamental pathophysiological aspect of this
      disease: attenuation of the prandial insulin response. The predominantly hepatic
      elimination profile and a lack of drug-drug interactions with repaglinide are
      also properties well suited for patients with Type 2 diabetes. Importantly, the
      pharmacokinetic properties of repaglinide, are expected to reduce the risk of
      hypoglycaemia in comparison to the conventional insulin secretagogues
      (sulphonylureas). A reduced risk of hypoglycaemia carries the advantage that
      patients are not obliged to consume meals at regular intervals supplemented by
      snacks, so caloric restriction is feasible and lifestyle not compromised. These
      theoretical advantages have now been largely borne-out by clinical studies and
      empirical experience. Placebo-controlled studies have consistently demonstrated
      the antidiabetic efficacy of repaglinide, with improvements having been shown in
      all indicators of glycaemic control. Double-blind, active-comparator studies have
      shown repaglinide to have an antidiabetic efficacy that is at least equivalent to
      sulphonylureas, even when food intake and dosing intervals were controlled
      according to the requirements of sulphonylureas. Pooled data from these studies
      have shown that the risk of severe hypoglycaemia is reduced by 60% (p = 0.03)
      when repaglinide is used in preference to sulphonylureas. There is also evidence
      that the blood glucose threshold at which symptoms of hypoglycaemia are perceived
      by patients may be better preserved during treatment with repaglinide than with
      sulphonylureas. Studies examining flexible prandial dosing with repaglinide have
      shown that good glycaemic control and a low risk of hypoglycaemia are achievable
      goals that are independent of the meal (and, hence, dosing) pattern chosen by the
      patient. Furthermore, when used in this way, repaglinide has not been associated
      with weight gain. In combination therapy, repaglinide has been shown to act in
      synergy with both metformin and troglitazone. The possibility of a 'new' basal
      bolus regimen combining repaglinide and exogenous (neutral protamine hagedorn)
      NPH insulin strategy has also been investigated.

PMID- 11249479
TI  - Report on the Royal Society of Medicine one day meeting on coronary artery
      disease--'Bench to Bedside'. 29th June 2000, London, UK.
AB  - A one day meeting was organised by the Royal Society of Medicine during the
      summer. This was a meeting of high value with excellent speakers and provided
      several snapshot views on the progress which has been made in understanding and
      treating coronary artery disease (CAD) from the perspective of the lab scientist
      to that of the practising clinician. It basically provided updates for three
      areas: pathophysiology/inflammation gene therapy imaging coronary arteries.

PMID- 11249480
TI  - Several options for antiviral treatment trials in multiple sclerosis--but which
      targets should be selected?
AB  - Involvement of viruses in the pathogenesis of multiple sclerosis (MS) is a long
      lived hypothesis, which is has not yet been proven nor refuted. This is partly
      due to difficulties in the evaluation of diagnostic findings on persistent
      infections by common viruses such as herpesviruses and endogenous retroviruses.
      Progress in antiviral treatment of central nervous system (CNS) herpesvirus
      infections has stimulated controlled trials of long-term therapy with acyclovir
      and valacyclovir in MS, but conclusive results are not yet available. Other
      treatment possibilities might include anti-retroviral therapy, as well as
      attempts to counteract the effects of viruses in triggering attacks of MS
      following upper respiratory tract infections. Before such trials are initiated,
      however, further diagnostic evidence of the involvement of target viruses seems
      warranted.

PMID- 11249481
TI  - Low molecular weight heparins.
AB  - Since its discovery, nearly 90 years, heparin has been used successfully for the
      treatment of thromboembolic processes. However, therapy with heparin has several
      important limitations. Most importantly, the poor predictability of its
      anticoagulant effects has led to the development of the low molecular weight
      heparins (LMWHs), which are derived from unfractionated heparin and appear to
      have pharmacologic advantages, require no laboratory monitoring and are more
      predictable than their parent compounds. LMWHs have been used for several years
      in the treatment of venous thromboembolic disorders. More recently, the LMWHs
      have been used to treat patients with acute coronary interventions. As the
      results of new studies are revealed, we will learn whether the use LMWH can be
      extended to all disorders where unfractionated heparin is currently the standard
      therapy.

PMID- 11249482
TI  - Pharmacotherapy following myocardial infarction--a review of current treatment
      practices.
AB  - Modern treatment of acute myocardial infarction (AMI), including thrombolysis and
      early interventional strategies, has reduced mortality rates but increased the
      number of patients requiring medical treatment. Post infarction treatment with
      aspirin, statins, beta-blockers and angiotensin-converting enzyme (ACE)
      inhibitors has improved morbidity and mortality and is cost-effective. The major
      successes of secondary prevention have been seen in the prevention of
      reinfarction, recurrent ischaemia and the development of heart failure. However,
      in spite of recent advances and increasing knowledge, the mortality rates remain
      high, partly due to the under use of the established and documented medical
      strategies. Implementation of the current treatment strategies into general
      practice remains a challenge. The field is undergoing rapid change due to the
      increasing use of early invasive strategies. The primary objective should remain
      the prevention of underlying aetiology: coronary artery disease (CAD). Secondary
      prevention following myocardial infarction (MI) will remain a major challenge in
      clinical practice within the foreseeable future.

PMID- 11249483
TI  - Immunotoxins.
AB  - Immunotoxins are molecules which contain a protein toxin connected to a targeting
      antibody. The goal of therapy is for the molecule to bind selectively to cancer
      cells, or to cells mediating autoimmune disease, internalise and then for the
      toxin to kill the cell. Several immunotoxins meeting this definition are in
      preclinical and clinical development, but none are approved yet for use in
      general practice. One close relative of immunotoxins is the growth factor fusion
      toxin, wherein the targeting antibody is replaced with a growth factor that
      selectively binds and this ligand is fused in a recombinant fashion to a protein
      toxin. One such molecule, containing human interleukin-2 (IL-2) fused to
      truncated diphtheria toxin (DT), has recently been approved under the name Ontak,
      and others are under development. A newer class of immunotoxins, termed
      recombinant immunotoxins, contain the variable or antigen binding domains of an
      antibody fused in recombinant fashion to a toxin. Recombinant immunotoxins, like
      growth factor fusion toxins, can be produced efficiently from bacteria and have a
      defined structure with respect to the linkage between the toxin and the ligand.
      However, they can, like conventional immunotoxins, be directed to antigens other
      than growth factor receptors, including receptor subunits. Several recombinant
      immunotoxins are under clinical testing and major responses have been reported,
      particularly in haematological malignancies. Some of these molecules may enter
      clinical practice in the future as targeted therapy, which is a modality distinct
      from those of chemotherapy, surgery and radiation therapy.

PMID- 11249484
TI  - Novel combination chemotherapy in the treatment of non-small cell lung cancer.
AB  - Treatment of patients with advanced non-small cell lung cancer (NSCLC) remains a
      vexing problem and long-term survival beyond 5 years is extremely rare. Five new
      agents, paclitaxel, docetaxel, vinorelbine, gemcitabine and irinotecan, have been
      introduced for the treatment of NSCLC and investigated extensively both
      preclinically and clinically. Monotherapy with one of these agents has produced
      survival benefits over the best supportive care in Phase III studies. Combination
      chemotherapy with a new agent and platinum produced a higher response rate than
      conventional cisplatin-based chemotherapy and improved survival was observed in
      some randomised trials. There was little difference in efficacy and toxicity
      between the chemotherapeutic regimens with a new agent and a platinum in Phase
      III trials, suggesting the clinical utility of these regimens is similar. Many
      trials have focused on regimens containing two new agents, with or without
      platinum. Preliminary results of Phase III trials of three drug combinations
      versus two drug combinations suggested the former to be more promising, in terms
      of response rates and survival. Whether the era of platinum-based chemotherapy in
      the treatment of NSCLC should continue or not must be determined by Phase III
      trials, evaluating the use of a platinum agent with one of the new agent
      combinations. These aggressive chemotherapeutic combinations will hopefully
      improve survival and quality of life for patients with advanced NSCLC.

PMID- 11249485
TI  - HRT and its impact on the menopause, osteoporosis and breast cancer.
AB  - Hormone replacement therapy (HRT) is a widely used treatment for vasomotor
      symptoms of the menopause. In this respect, there is a wealth of randomised
      evidence that it is an effective and cost-effective treatment, achieving
      substantial quality of life gains for relatively low cost. On the other hand,
      potentially major health benefits lie in the prevention of chronic diseases such
      as osteoporosis and cardiovascular disease. Observational data strongly support
      the role in HRT's ability to prevent fractures; however, there is a suggestion
      that this antifracture benefit is only realised if treatment is taken soon after
      the menopause and is soon lost after cessation of treatment. HRT also increases
      the risk of breast cancer, which may negate much of its health benefit.

PMID- 11249487
TI  - Respiratory syncytial virus prevention: past and present strategies.
AB  - Respiratory syncytial virus (RSV) is a common cause of respiratory illness in
      young children, almost all will have been infected by the age of two years old.
      Very young infants, and those with underlying disease, are at risk of severe RSV
      disease, but even those who were previously healthy can suffer recurrent
      respiratory symptoms 9 to 10 years after their initial infection. The management
      of RSV infection is essentially supportive, thus prophylaxis offers the best hope
      of reducing the morbidity and mortality of RSV infection. There is no safe and
      effective RSV vaccine to use in those infants who are at highest risk from the
      infection. Immunoprophylaxis, however, has been shown to have benefits in
      randomised controlled trials. Standard immunoglobulin, however, is ineffective as
      its administration does not achieve an adequate titre of neutralising antibodies.
      RSV immunoglobulin (RSV-IGIV, RespiGam, Massachusetts Public Health Laboratories,
      Boston, MA), in contrast, contains high levels of RSV neutralising antibody and
      has been shown to significantly reduce hospitalisation in preterm infants with or
      without bronchopulmonary dysplasia (BPD). Its use is not recommended in infants
      with cyanotic congenital heart disease (CHD), as it was associated with an excess
      of adverse events. A humanised RSV monoclonal antibody (Palivizumab, MEDI-493,
      Synagis, MedImmune Inc, Gaithersburg, MD) also significantly reduces
      hospitalisation for RSV infection in high risk infants, but without serious side
      effects. The American Academy of Paediatrics has recommended that
      immunoprophylaxis should be considered for young children at high risk of severe
      RSV infection and that palivizumab is the preferred agent. Studies have suggested
      it is essential to carefully select patients for immunoprophylaxis, if its use is
      to be cost-effective.

PMID- 11249486
TI  - Proton pump inhibitors in the treatment of gastro-oesophageal reflux disease.
AB  - Gastro-oesophageal reflux disease (GERD) is the most common peptic acid disease
      in the western world and is the commonest indication for acid suppression
      therapy. Major advances have been made over the past 30 years in the
      understanding of lower oesophageal sphincter function and the mechanism of acid
      secretion. Developments in surgical and pharmacological therapy have paralleled
      these advances. Pharmacotherapy for GERD has evolved from antacids to H2-receptor
      antagonists (H2RAs) to prokinetics to proton pump inhibitors (PPIs). The H2RAs,
      while modestly effective in symptom relief and healing of GERD, are limited by
      pharmacological tolerance. The prokinetics (metoclopramide and cisapride) are
      limited by low efficacy, pharmacological tolerance and toxicity. The PPIs have
      emerged as the most effective therapy for symptom relief, healing and long-term
      maintenance. They have also proved to be remarkably safe and cost-effective in
      long-term therapy. This review evaluates the pharmacology, efficacy,
      tolerability, safety and cost-effectiveness of the four currently available PPIs,
      lansoprazole, omeprazole, pantoprazole and rabeprazole, in the treatment of GERD.

PMID- 11249488
TI  - Current treatment of sepsis and endotoxaemia.
AB  - This article reviews the new criteria for selecting the proper antimicrobial
      agent and dosage regimen for standard treatment of severe sepsis, with the
      intention of preventing septic shock. After introducing new concepts on the
      pathogenesis of sepsis and septic shock, the authors analyse the parameters of
      beta-lactam antibacterial activity, the antibiotic-induced release of bacterial
      endotoxin and the interrelationships between pharmacokinetics and
      pharmacodynamics of antibiotics in the search for an optimum dosage regimen of
      antimicrobial mono- or polytherapy for severely ill septic patients admitted to
      the intensive care unit. The mortality rate resulting from severe bacterial
      sepsis, particularly that associated with shock, still approaches 50% in spite of
      appropriate antimicrobial therapy and optimum supportive care. Bacterial
      endotoxins that are part of the cell wall are one of the cofactors in the
      pathogenesis of sepsis and septic shock and are often induced by antimicrobial
      chemotherapy, even if administered rationally. Not all antimicrobial agents are
      equally capable of inducing septic shock; this is dependent on their mechanism of
      action rather than on the causative pathogen species. The quantity of endotoxin
      released depends on the drug dose and whether filaments or spheroplast formation
      predominate. Some antibiotics, such as carbapenems, ceftriaxone, cefepime,
      glycopeptides, aminoglycosides and quinolones, do not have the propensity to
      provoke septic shock because their rapid bacterial activity induces mainly
      spheroplast or fragile spheroplast-like bacterial forms.

PMID- 11249489
TI  - Recent approaches to periodontal therapy.
AB  - Periodontal diseases encompass a variety of disease classifications, all
      involving inflammation of the supporting tissues of the teeth. When progressive,
      these diseases ultimately lead to the destruction of attachment apparatus
      including bone and periodontal ligament, culminating in eventual tooth loss.
      Inflammation extends from superficial gingival structures, effecting adjacent
      submerged bone and periodontal ligament. Progression modifies an initially highly
      favourable, reversible diagnosis of gingivitis to a less favourable, somewhat
      irreversible situation: periodontitis. Periodontal diseases manifest variable and
      sometimes unpredictable prognoses, are generally somewhat complicated and costly
      to treat and often require long-term follow-up for maintenance and monitoring.
      Treatment aims at restoration of health and control of future disease within a
      functional, albeit reduced, periodontium. In the strictest sense, periodontal
      diseases are not 'cured'. The conventional, usually successful, approach to the
      treatment of patients with gingivitis or chronic periodontitis has involved non
      surgical mechanical periodontal therapy [1,2]. Some patients manifest localised
      or generalised continuous attachment loss and periodontal destruction. These
      sites are prime candidates for alternative therapeutic regimens. This review
      highlights some of the recent advances in periodontal therapy and evokes some
      questions that should be addressed during future studies.

PMID- 11249490
TI  - Fluticasone propionate: a potent inhaled corticosteroid for the treatment of
      asthma.
AB  - Fluticasone propionate (FP) is a potent inhaled corticosteroid (ICS) for the
      treatment of asthma. It is currently marketed in both the United States (as
      Flovent) and Europe (as Flixotide). Fluticasone is available in both aerosolised
      metered dose inhaler (MDI) and dry powder devices, with dosages ranging from 44
      500 micrograms/puff. FP has been extensively studied in both children and adults;
      efficacy has been documented across the entire spectrum of asthma severity,
      including corticosteroid-dependent disease. Clinical data with FP strongly
      corroborates the in vitro pharmacokinetic and pharmacodynamic studies that FP is
      at least twice as potent as beclomethasone dipropionate (BDP), budesonide (BUD)
      or triamcinolone acetonide (TAA). Both objective (lung function) and subjective
      (symptoms, beta-agonist use and quality of life) outcomes are improved with FP
      treatment. Extensive post-marketing surveillance with FP suggests that it is more
      cost-effective than BUD and flunisolide (FLU) when analysed by an overall
      healthcare cost perspective. Most of the benefits arise from decreased
      hospitalizations, emergency room visits and physician-office visits. Extensive
      safety data with FP documents no clinically meaningful effects on bone mass, nor
      impairment of growth velocity in children. Considering the efficacy and safety
      data along with the ability to optimise patient's asthma therapy using the
      delivery devices and strengths available, FP has become a leader in the ICS
      marketplace to date.

PMID- 11249491
TI  - An assessment of zonisamide as an anti-epileptic drug.
AB  - A brief review of epilepsy as a disease, anti-epileptic drugs and methods of
      evaluation of anti-epileptic drugs are presented as a background for assessment
      of zonisamide, which has been approved by the FDA as add-on therapy for the
      treatment of partial seizures with or without secondary generalisation in adults.
      Chemically, zonisamide is classified as a sulphonamide and is unrelated to other
      anti-epileptic drugs. The mode of action of zonisamide remains unclear, but
      likely mechanisms are blockade of sodium and T-type calcium channels. It is also
      shown to have some neuroprotective effect against hypoxia and ischaemia. It has a
      liner pharmacokinetics with excellent oral bioavailability. Zonisamide has been
      approved for use in Japan for ten years prior to approval in USA and Europe.
      Clinical experience with zonisamide in Japan has documented its efficacy in the
      treatment of partial seizures (partial-onset generalised tonic-clonic, simple
      partial and/or complex partial seizures) and to a more variable extent,
      generalised tonic-clonic, generalised tonic (mainly seen in symptomatic
      generalised epilepsies including Lennox-Gastaut Syndrome) and
      compound/combination seizures. The efficacy and safety was confirmed in trials
      conducted in USA and Europe in adults as well as children. Zonisamide compares
      favourably with other newly introduced drugs and has the potential for
      development as a monotherapy for epilepsy.

PMID- 11249492
TI  - Evaluation of current pharmacotherapy of chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a severe chronic respiratory
      condition characterised by progressive, irreversible airflow limitation. It is
      common, affecting more than 16 million people in the United States and is the
      fourth highest cause of death. The worldwide incidence of COPD is increasing and,
      in parallel, the economic and social burden the disease incurs. The treatment of
      COPD is symptomatic, with no drugs currently available to halt the relentless
      progression of airflow obstruction. However, with a better understanding of the
      pathological features of the airway inflammation and alveolar destruction that
      characterises COPD, new therapeutic strategies are being developed. This article
      provides a critical evaluation of current pharmacotherapy in COPD, essentially
      bronchodilators (anticholinergics, beta 2-adrenoceptor agonists and theophylline)
      and corticosteroids, and an overview of international recommendations for their
      use.

PMID- 11249493
TI  - Current treatment of asthma--focus on leukotrienes.
AB  - Since their identification in 1979, the cysteinyl leukotrienes (cysLTs) have been
      shown to be prominent in many inflammatory conditions, including asthma, allergic
      rhinitis, rheumatoid arthritis, psoriasis, cystic fibrosis and inflammatory bowel
      disease. They are potent pro-inflammatory agents, as well as causing
      bronchoconstriction, and undoubtedly have a role in asthma. The cysLTs are
      products of arachidonic acid metabolism and have been shown to have effects via a
      cysteinyl leukotriene receptor (CysLTR1) on vascular permeability, mucus
      production, chemotaxis and bronchial smooth muscle. Their detection in certain
      body fluids in allergic, aspirin-sensitive and exercise-induced asthma is well
      documented and potential roles in pathogenesis, proposed. The development of
      agents affecting production or action offers an exciting new approach to the
      treatment of asthma. Two approaches to antileukotriene therapy have been
      developed: blocking their production by inhibiting the action of 5-lipoxygenase
      enzyme or blocking the CysLTR1. Both approaches have been tried in studies in
      asthma and overall the results are encouraging, with a decrease in both daytime
      and nocturnal symptoms, a decrease in additional beta 2 agonist usage and
      improvement in lung function. The changes, however, are small in some studies.
      This may be a reflection of disease severity in the study subjects, but of note
      is a heterogeneity of response to these treatments that may be genetically
      determined. Antileukotriene therapy has been shown to have an effect in specific
      types of asthma where the role of cysLTs seems well established--aspirin
      sensitive/intolerant asthma and exercise-induced asthma. Longer term studies are
      needed in other areas such as severe asthma and chronic persistent asthma in both
      children and adults to provide evidence for the appropriate placement of
      antileukotriene treatment in current asthma guidelines, in comparison with other
      established treatments.

PMID- 11249494
TI  - Tumour necrosis factor-alpha blockade: a new era for effective management of
      rheumatoid arthritis.
AB  - Tumour necrosis factor (TNF)-alpha inhibitors have emerged as a new treatment
      option for rheumatoid arthritis (RA). The scientific rationale for targeting TNF
      alpha in RA derives from extensive work in the laboratory, showing the importance
      of this pro-inflammatory cytokine as a mediator of joint inflammation. Proof of
      principle has now been firmly established in clinical trials where TNF-alpha
      inhibitors have been shown to decrease the signs and symptoms of joint
      inflammation and slow radiological progression of joint damage. Presently, the
      two TNF-alpha inhibitors available for use in RA are etanercept and infliximab.
      Etanercept is a soluble TNF receptor: Fc fusion protein that competes with the
      endogenous TNF receptors for TNF-alpha binding. Infliximab is a chimeric anti-TNF
      alpha monoclonal antibody, which also binds with high affinity to soluble TNF
      alpha. Etanercept and infliximab will be rapidly incorporated into current
      treatment paradigms, which call for early and intensive treatment of RA using
      disease-modifying antirheumatic drugs (DMARDs), such as methotrexate,
      sulfasalazine and hydroxychloroquine. A major drawback to the widespread use of
      these biologics is their high costs. Some patients with limited financial means
      may be denied access to these effective anti-inflammatory agents. Moreover, long
      term experience with TNF-alpha inhibitor therapy has been limited and concerns
      linger about the possibility that etanercept and infliximab may cause unforeseen
      side effects or increase the risk for opportunistic infection. Despite these
      caveats, TNF-alpha inhibitors represent a major advance for the treatment of RA
      and will likely spawn new indications for anti-TNF-alpha therapy and the
      development of novel therapeutic compounds with similar biological activity.

PMID- 11249495
TI  - Rofecoxib.
AB  - Rofecoxib (Vioxx, Merck & Co., Inc.) is a new orally-effective non-steroidal anti
      inflammatory drug (NSAID) approved for treatment of acute pain, fever, primary
      dysmenorrhea and pain and inflammation in osteoarthritis (OA). It is also being
      evaluated for treatment of rheumatoid arthritis and adenomatous polyps of the
      colon. Rofecoxib is a specific inhibitor of cyclooxygenase-2 (COX-2), thereby
      inhibiting prostanoid synthesis in cells that express COX-2, including
      inflammatory cells. As cells in the gastrointestinal (GI) tract principally
      express COX-1, a different isoform of cyclooxygenase, it is predicted that
      rofecoxib will have less GI toxicity than other less selective NSAIDs. In
      clinical trials, rofecoxib was found to be as effective as other NSAIDs for
      management of pain and inflammation. In trials that compare rofecoxib with
      ibuprofen, diclofenac and indomethacin, less GI toxicity has been observed, as
      assayed by a decrease in lesions visible on endoscopy, by GI blood loss and, in a
      meta-analysis, by frequency of serious adverse GI events. The presence of COX-2
      in cells other than inflammatory cells results in side effects common among
      NSAIDs, including peripheral oedema and hypertension. These side effects are dose
      dependent. Rofecoxib, together with other branded NSAIDs, are relatively
      expensive, which has led to concern regarding costs versus benefits. There is
      also concern regarding potential risks associated with the use of rofecoxib by
      populations that would otherwise not tolerate NSAIDs.

PMID- 11249496
TI  - Summary from the 153rd meeting of the American Psychiatric Association. 13-18 May
      2000, Chicago, Illinois, USA.
AB  - The annual meeting of the American Psychiatric Association focuses on a variety
      of topics, including those on psychopharmacology. The latest developments are
      typically those found in the New Research sections, which is where this summary
      will focus.

PMID- 11249497
TI  - Pharmacotherapy of gastroparesis.
AB  - The evaluation and management of gastric motor dysfunction continues to represent
      a significant clinical challenge. The very definition of what constitutes a
      clinically relevant disturbance of gastric motility remains unclear. The spectrum
      of gastroparesis extends from those with classical symptoms and severe delay of
      gastric emptying to those with dyspepsia and a mild delay in emptying rate.
      Indeed, for many patients with dyspepsia, the role of gastric emptying delay in
      the pathogenesis of symptoms, remains unclear. Any assessment of the efficacy of
      any therapeutic class in gastroparesis must be mindful, therefore, of these
      variations in definition. For those individuals with severe established
      gastroparesis, therapeutic success often remains elusive and i.v. erythromycin
      and oral dopamine antagonists, or substituted benzamides, remain the best options
      for acute severe exacerbations and chronic maintenance therapy, respectively.
      Alternatives, currently under investigation, include a number of 5-HT4 agonists,
      macrolides devoid of antibiotic activity, CCK antagonists and gastric electrical
      stimulation. Other novel approaches include strategies to address some of the
      regional abnormalities in gastric motor function that have been identified in
      some patients with dyspepsia.

PMID- 11249498
TI  - Prospects for the treatment of Parkinson's disease using neural grafts.
AB  - Parkinson's disease (PD) is an incurable neurodegenerative condition of the
      central nervous system (CNS) that typically presents in the fifth to seventh
      decade of life, with a movement disorder that consists of a resting tremor,
      bradykinesia and rigidity. It is a disease that can only be diagnosed with
      certainty at postmortem when the pathological hallmark is loss of the
      dopaminergic nigrostriatal pathway and presence of Lewy bodies in the substantia
      nigra. However, pathological changes, including Lewy body formation, are found
      outside of the nigrostriatal system and involve other neurotransmitters, which
      may also account for some of the cognitive, psychiatric and autonomic
      abnormalities in these patients. To date, the mainstay of treatment for patients
      with PD has been drugs that activate the dopaminergic network, namely the
      dopamine precursor L-dopa and dopamine receptor agonists. However, recently
      interest has turned towards more curative therapies, including the use of grafts
      of neural tissue to replace dopaminergic neurones that have been lost. This
      approach has now entered clinical trials and this review will analyse the
      therapeutic approach of neural grafting in PD.

PMID- 11249499
TI  - Women's issues in mood disorders.
AB  - Since the introduction of antidepressants in the 1950s, it was assumed for the
      next several decades that there were no special reasons to look at the
      application of these medications to women. In the past half-century, particularly
      in the past decade, since the advent of the selective serotonin re-uptake
      inhibitors (SSRI), a series of specific foci have developed. Firstly, there
      appear to be differences in the degree of response to particular antidepressants
      between the genders. Secondly, there is data concerning hormonal effects of
      particular relevance to women, i.e. prolactin, which separates out among the
      antidepressants. Also of concern to women are the potential teratogenic effects
      of these medications, which impact on their use during pregnancy. Finally, there
      are certain diagnostic syndromes that are particularly relevant to women:
      premenstrual dysphoric disorder (PMDD); postpartum depression (PPD) and
      perimenopausal depression (PMD). It appears that the SSRIs may be more effective,
      relative to the older tricyclic antidepressants (TCA), in women than in men. The
      SSRIs have shown to be effective in treating these disorders, with the
      possibility of intermittent luteal phase treatment of PMDD. Non-antidepressant
      (AD) approaches have generally been found to be less effective. In the first
      trimester of pregnancy, there is data available supporting the safe use of SSRIs,
      particularly those first released, i.e. fluoxetine and sertraline. Finally, all
      SSRIs, with the exception of sertraline, can increase the risk of
      hyperprolactinaemia. This can lead to a variety of complications including
      amenorrhea and osteoporosis. This effect of sertraline, due to its unique profile
      in blocking re-uptake of dopamine, extends itself into additional relative
      benefits for sleep and memory. The issues associated for women with bipolar
      disorder are dealt with in terms of both increased risk of relapse during
      pregnancy and postpartum periods, as well as the relative risk of use of lithium
      and mood stabilizers in pregnancy and lactation.

PMID- 11249500
TI  - Selective serotonin reuptake inhibitors: a review of efficacy and tolerability in
      depression.
AB  - Selective serotonin reuptake inhibitors (SSRIs) are now generally regarded as
      effective and better tolerated alternatives to tricyclic antidepressants (TCAs)
      for the treatment of depression. SSRIs also seem to be as well tolerated as
      moclobemide, mirtazapine, venlafaxine, reboxetine and nefazodone and show
      comparable efficacy. Minor differences have been observed between some SSRIs and
      some of the newer antidepressants but these findings are far from conclusive.
      Widespread use of the SSRIs has highlighted some unforseen adverse effects
      associated with SSRIs, namely hyponatraemia, EPSE and sexual dysfunction.
      Overall, differences in efficacy and tolerability between individual SSRIs are
      small and clinically insignificant.

PMID- 11249501
TI  - Paediatric uses of atypical antipsychotics.
AB  - Antipsychotics are commonly prescribed to children and adolescents. With the
      relatively recent availability of the atypical antipsychotics, physicians have
      begun prescribing these agents to young people in the hope of finding safe,
      effective alternatives to the typical antipsychotics. This report reviews what is
      currently known about the use of the atypical antipsychotics in young people.
      Most of the currently available data are based on case reports and case series.
      The results of only a handful of prospective trials pertaining to the use of the
      atypical antipsychotics in youths have been reported. Based on the available
      information, it appears that clozapine has a role in juvenile treatment resistant
      schizophrenia. When considered as a group, the 'first-line' atypical
      antipsychotics risperidone, olanzapine and quetiapine appear to have promise as
      treatments for several neuropsychiatric disorders in young people. These
      conditions include psychotic, mood, disruptive, movement and pervasive
      developmental disorders. Unfortunately, as has historically been the case, the
      demand to address the clinical needs of young patients with neuropsychiatric
      disorders has outpaced empirically based information. This is particularly
      important because significant side effects can occur when children or adolescents
      are treated with atypical antipsychotics. Since there is a paucity of short-term
      and almost no long-term safety data pertaining to these agents in young people,
      careful consideration must be made prior to initiating atypical antipsychotic
      treatment for a child or teenager. Based upon what is known about these agents, a
      rational approach to the use of these drugs in juveniles is offered.

PMID- 11249502
TI  - Drugs that prolong QT interval as an unwanted effect: assessing their likelihood
      of inducing hazardous cardiac dysrhythmias.
AB  - Medicinal products that, as an unwanted effect, prolong the QT interval of the
      electrocardiogram (ECG) can trigger episodes of polymorphic ventricular
      dysrhythmias, called torsades de pointes, which occasionally culminate in sudden
      death. The accurate measurement of QT interval requires the adoption of
      appropriate criteria of recording, measurement and data processing.
      Traditionally, QT interval is standardised to a reference heart rate of 60
      beats/min by using the Bazett algorithm. However, this correction method can bias
      observed QT intervals in either direction. The ECG reflects cardiac electrical
      currents generated by ions (Na+, K+ and Ca2+) entering and leaving the cytosol
      mainly via transmembrane channels. Na+ and Ca2+ carry inward depolarising
      currents (INa, ICa) whereas K+ carries outward repolarising currents (Ito, IKr,
      IKS and IK1). Sometimes, a prolonged QT interval is a desired drug effect but,
      more commonly it is not, and reflects abnormalities in cardiac repolarisation
      heralding torsades de pointes. Furthermore, the potential torsadogenic activity
      of drugs is favoured by concurrent cardiac risk factors (old age, female gender,
      bradycardia, electrolyte imbalances, cardiac diseases etc.) which reduce cardiac
      repolarisation reserve. The evaluation of the cardiac safety of drug candidates
      can be started by determining their potency as IKr blockers in cloned Human Ether
      a-go-go Related Gene (HERG) channels expressed in mammalian cells. Compounds
      passing successfully this test (desirable cardiac safety index > 30, calculated
      as ratio of IC50 against IKr over ED50 determined in an efficacy test) should be
      further investigated in other relevant human cardiac ion currents, in in vitro
      animal heart preparations and finally in in vivo pharmacodynamic models. The
      decision as to whether the potential benefit of a new drug outweighs the cardiac
      risk inherent in its therapeutic use should be made in the light of the condition
      that it is expected to treat and with reference to alternative drug therapies. If
      a drug represents a unique therapeutic advance, non-clinical and clinical signals
      of unsatisfactory cardiac safety may not constitute sufficient grounds to abandon
      its development. However, if the drug offers only marginal benefits over existing
      therapies, decisions concerning its possible development should be taken by
      corporate policy makers.

PMID- 11249503
TI  - Growth hormone: current and future therapeutic applications.
AB  - The increased availability of growth hormone (GH) in the mid-1980s, as a result
      of advances in recombinant DNA techniques, has allowed research into the use of
      this hormone at physiological dosage, as replacement therapy for adults with GH
      deficiency (GHD) and at pharmacological dosages as a possible therapeutic agent,
      for a number of disease states. GHD adults have increased body fat and reduced
      muscle mass and consequently, reduced strength and exercise tolerance. In
      addition, they are osteopenic, have unfavourable cardiac risk factors and
      impaired quality of life. In these individuals, replacing GH reverses these
      anomalies, although it may not alter the reduced insulin-sensitivity. A
      proportion of adults with GHD perceive a dramatic improvement in their well
      being, energy levels and mood following replacement. GH has protein and
      osteoanabolic, lipolytic and antinatriuretic properties. GH has been considered
      for the therapeutic treatment of frailty associated with ageing, osteoporosis,
      morbid obesity, cardiac failure, major thermal injury and various acute and
      chronic catabolic conditions. Initial small, uncontrolled studies for many of
      these clinical problems suggested a beneficial effect of GH, although, later
      placebo-controlled studies have not observed such dramatic effects. Furthermore,
      with a recent publication demonstrating an approximate 2-fold increase in
      mortality in critically ill patients receiving large doses of GH, the use of GH
      should remain in the realms of replacement therapy and research, until there are
      significant advances in our understanding.

PMID- 11249504
TI  - Current management of acromegaly.
AB  - Acromegaly, a chronic disease of growth hormone (GH) hypersecretion, is most
      typically caused by a pituitary adenoma. Early diagnosis is critical for prompt
      intervention to prevent deleterious effects of prolonged exposure to elevated GH
      and insulin-like growth factor Type I (IGF-I) levels. Current therapy for
      acromegaly includes several options: surgery, radiotherapy and pharmacotherapy.
      Transsphenoidal adenomectomy remains a mainstay of therapy for acromegaly. Cure
      rates are high in microadenomas, but < 50% in macroadenomas. Conventional and
      stereotactic procedures for radiation therapy are also effective in decreasing GH
      levels in acromegalic patients, but they need years to normalise GH
      hypersecretion and carry with them the risk of hypopituitarism. The major classes
      of drugs currently used to treat acromegaly are dopamine agonists and analogues
      of somatostatin. Dopamine agonists bind to the D2 receptor and suppress GH
      hypersecretion in some patients with acromegaly. Their clinical effectiveness is
      modest, although promising results have been obtained with two novel compounds,
      quinagolide and cabergoline, that possess long duration of action. Somatostatin
      analogues have been shown to improve clinical symptoms of acromegaly, decrease
      hypersecretion of GH and IGF-I and reduce tumour volume in a clinically
      significant number of patients. Octreotide is administered by s.c. route several
      times a day, but the recently developed sustained release formulations
      (octreotide LAR and SR lanreotide) are administered only every 7-28 days by i.m.
      injections. The complications associated with somatostatin analogues are small,
      relative to the benefits. Lastly, compounds with a novel mechanism of action, the
      GH receptor antagonists, are presently under investigation.

PMID- 11249505
TI  - Innovations and strategies for the development of anticancer vaccines.
AB  - In 1893, William Coley reported the spontaneous regression of a soft tissue
      sarcoma in several patients suffering from acute bacterial infections. Although
      this observation occurred over a century ago, the concept of anticancer vaccines
      and the immunotherapy of cancer has only recently seemed plausible. A myriad of
      specific and non-specific immunostimulatory approaches have been tested
      throughout the years with only a modicum of success. Most of these approaches
      were doomed from the outset since they were based on false or inadequate
      knowledge of tumour immunology. Recent advances in our understanding, most
      notably the identification of genes encoding for cancer regression antigens,
      currently permit investigators to pursue a more cogent strategy to develop novel
      and specific anticancer vaccine approaches. Several of these approaches are
      currently being tested in clinical trials and have already yielded exciting
      results. However, a number of immunologic and host obstacles to the successful
      application of anticancer vaccines remain. This editorial will provide an update
      on the clinical status of anticancer vaccines and review areas of promising
      research initiatives.

PMID- 11249506
TI  - TNF-alpha antagonists for the treatment of Crohn's disease.
AB  - New medical therapies that inhibit the bioactivity of TNF-alpha represent a major
      breakthrough in the treatment of Crohn's disease (CD). Anti-TNF-alpha,
      monoclonal, chimeric antibody (infliximab) is now FDA approved for use in
      patients with active CD. Other investigational drugs that also inhibit TNF-alpha
      activity include new 'humanised' anti-TNF-alpha antibodies (CDP571), thalidomide,
      new analogues of thalidomide, and TNF-alpha receptor fusion proteins. This review
      will summarise the key clinical data for each of these categories of TNF-alpha
      inhibition and discuss the potential economic impact of these new compounds on
      the cost of CD management.

PMID- 11249507
TI  - Replicating herpes simplex virus vectors for cancer gene therapy.
AB  - Attenuated viral vectors based on herpes simplex virus (HSV) are capable of
      killing cancer cells directly while sparing normal tissue in animal models of
      disease. This selective ability is likely due to the evolutionary constraints on
      the virus to establish lifelong infection in its host without causing destruction
      of normal tissues. However, extensive experimental animal data show that cancer
      cells are able to sustain a productive viral infection, which ultimately leads to
      cell death and tumour regression. Moreover, preliminary results generated in two
      Phase I clinical studies of modified replicating HSV for the treatment of brain
      tumours (e.g., glioblastoma multiforme) have been encouraging and suggest that
      the safety data generated in animals are predictive of human safety. Although
      much progress has been made in developing oncolytic HSV vectors for clinical use,
      there is still a long way to go to determine which combinations of virus,
      surgery, radiation and chemotherapy will provide improved therapy for the control
      and eradication of a variety of human cancers.

PMID- 11249508
TI  - New anti-epileptic drugs for the 21st century.
AB  - Prior to 1993, there were only six major drugs available in the US for the
      treatment of patients with epilepsy. These included phenobarbital (PB), phenytoin
      (PHT), carbamazepine (CBZ), primidone (PRIM), valproic acid/sodium valproate
      (VPA) and ethosuximide (ESX). Of these drugs, VPA has the broadest spectrum of
      activity and ESX the most limited. Despite these six agents, as well as several
      secondary drugs, it is estimated that over 30% of patients have inadequate
      seizure control, while others, whose disease is adequately controlled, suffer
      from bothersome adverse events (AEs). Since 1993, ten new drugs have entered the
      worldwide market (not all in the US). Those released include felbamate (FBM),
      gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB),
      oxcarbazepine (OXC), levetiracetam (LVT), zonisamide (ZNS), clobazam (CLB) and
      vigabatrin (VGB). The purpose of this article is to review each of the above
      drugs, looking at efficacy, safety, tolerability and where they may play a role
      in the current treatment of epilepsy.

PMID- 11249509
TI  - Critical appraisal of the JNC VI, WHO/ISH and BHS guidelines for essential
      hypertension.
AB  - Three guidelines have been selected for this review: The Sixth Report of the
      Joint National Committee on Prevention, Detection, Evaluation and Treatment of
      High Blood Pressure (JNC VI), the 1999 World Health Organization-International
      Society of Hypertension Guidelines for the Management of Hypertension (WHO/ISH)
      and the Guidelines for management of hypertension: report of the third working
      party of the British Hypertension Society (BHS). The guidelines are generally in
      accordance on the principles of drug prescribing. There is, however, a serious
      divergence of opinion between JNC VI and BHS, and WHO/ISH on the levels of blood
      pressure chosen for defining hypertension and the level to which blood pressure
      should be reduced. In defining hypertension using ambulatory blood pressure
      measurement (ABPM), JNC VI and BHS recommendations for systolic blood pressure
      are 10-15 mmHg higher than WHO/ISH. There is even greater divergence of opinion
      between the guidelines on the recommended goals of treatment. Using conventional
      measurement WHO/ISH recommends lowering systolic blood pressure with treatment by
      10-20/5-10 mmHg more than JNC VI and BHS depending on whether 'normal' or
      'optimal' pressures are to be achieved. Using average daytime ABPM pressure,
      WHO/ISH recommends lowering the average daytime blood pressure with treatment by
      10-30/5-10 mmHg more than JNC VI and BHS depending on whether 'normal' or
      'optimal' blood pressures are chosen. These differing recommendations between JNC
      VI and BHS, and WHO/ISH cannot be reconciled and they are of such magnitude as to
      carry serious implications for clinical practice, not least among which is that
      acceptance of the WHO/ISH levels of 'normality' for blood pressure would result
      in some 45% of the population of all ages and nearly 60% of elderly people being
      classified as 'hypertensive'.

PMID- 11249510
TI  - Pharmacotherapy of hypercholesterolaemia: statins in clinical practice.
AB  - The objective of this article is to evaluate the roles of the lipid-lowering
      class of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors
      (statins) in reducing cardiovascular events and to review their mechanism of
      action based on in vitro and in vivo studies. The clinical outcome of 15 major
      clinical trials has been critically reviewed and summarised; all showed a high
      degree of efficacy and safety. Statins, either in active or prodrug forms, are
      potent inhibitors of HMG-CoA reductase, have good absorption rate and their
      bioavailability depends on their lipophobicity and concomitant use with meals.
      Abdominal discomfort is the most commonly reported adverse effect. Although the
      incidence is low, myopathy with or without rhabdomyolysis may be considered a
      serious adverse effect of statins. A combination of a statin with gemfibrozil
      seems to increase the risk of this adverse event, particularly in patients with
      renal impairment. Combination therapy with several other agents, frequently
      administered to cardiovascular patients, has also been reviewed. Statin therapy
      is considered highly cost effective in secondary prevention, but it is less cost
      effective in primary prevention. This factor may underline the rationale for
      developing other safe and effective agents with an improved cost effectiveness
      profile. The pleiotropic non-lipid lowering effects of statins may include their
      anti-oxidant and antithrombotic potential as well as restoration of endothelial
      function. Statins may also be beneficial in the treatment of osteoporosis. Fewer
      studies have investigated statins' effects on the quality of lipoprotein
      particles, the activities of cholesteryl ester transfer protein and
      lecithin:cholesterol acyltransferase as well as their possible synergistic
      effects with n-3 fatty acids, anti-oxidants and aspirin in reducing
      cardiovascular events.

PMID- 11249511
TI  - Pharmaceutical management of the childhood glaucomas.
AB  - Glaucoma in childhood is a diverse, blinding group of conditions, which presents
      a major therapeutic challenge. Treatment is primarily surgical with medical
      treatments used as an adjunct. None of these drugs has been granted approval by
      the regulatory agencies for use in children, but they are used on a compassionate
      basis. Issues of efficacy and safety of these medications in children are
      discussed. beta-adrenoceptor blockers have been employed as first line
      pharmaceutical therapy for many years. Recently three new classes of drugs have
      been developed for use in glaucoma in adults. beta-blockers remain first line
      therapy if there are no contraindications such as asthma. Topical carbonic
      anhydrase inhibitors (CAI) appear to be less effective than beta-blockers, but
      seem safe systemically, although associated with local irritation. They are
      useful as an adjunct to beta-blockers or as first line therapy when beta-blockers
      are contraindicated. Prostaglandins have not proved as effective in childhood
      glaucoma as in adult glaucoma, although it works well in some patients with
      juvenile open angle glaucoma (JOAG) and others with aphakic glaucoma. alpha
      adrenergic agonists, although effective at least in the short-term, have serious,
      potential systemic side effects, which demand close observation when used in
      neonates and young infants.

PMID- 11249512
TI  - Emerging concepts in the management of the malignant haematological disorders.
AB  - A comprehensive review of novel cytoreductive agents is presented. Such novel
      agents may be found among chemical compounds directed against specific molecular
      targets (cytostatics) or within the biological substances selectively aimed at
      the malignant clone (immunotherapy). It is stated that the purposes of
      immunotherapy in general are to generate a T-lymphocytic response against the
      tumour cells, e.g., graft versus leukaemia (GvL) effect, natural killer T-cell
      cytolysis, antibody-dependent cytolysis etc.; or to reprogramme the immune system
      of the tumour-bearing host by DNA and/or RNA manipulation with subsequent
      interference with the signalling pathway in the tumour cells. Some
      immunotherapeutic modalities are shortly described: donor T-lymphocyte infusion
      and GvL effect, polyclonal antibodies, monoclonal antibodies, vaccines, gene
      replacement therapy, suicide gene therapy, antisense oligonucleotides,
      alterations of DNA-RNA transcript factors and malignant antigenic drive etc. Most
      likely, a sequence of different treatment modalities will be used in the future
      comprising an initial debulking by means of standard chemotherapy and/or
      irradiation followed by target unspecific immunotherapy (polyclonal
      immunoglobulins, GvL effect etc.) and finally target specific elimination of
      residual tumour, probably with repeated use of the minimum effective
      pharmacologic dose (MEPD) of the agents used. In contrast, the current use of
      high-dose myeloablative chemotherapy with the use of maximum tolerable dose (MTD)
      and associated severe organ toxicity, and high rates of secondary malignancies
      will probably be substituted in the future. An effective supportive treatment
      will be highly necessary, especially related to prevention and treatment of
      infections.

PMID- 11249514
TI  - Pharmacotherapeutic agents in xenotransplantation.
AB  - The ability to transplant pig organs into humans would resolve the current crisis
      in the supply of cadaveric human organs for the treatment of end stage disease.
      Several immunologic barriers need to be overcome if pig-to-primate
      transplantation is to be successful. The presence of preformed antibodies in
      humans, apes and Old World monkeys directed against galactose epitopes on pig
      vascular endothelium provides the major barrier, as binding of antibody to
      antigen leads to graft destruction by complement activation and other mechanisms.
      Hyperacute rejection can result from the action of complement. If this is
      prevented, delayed antibody-mediated rejection develops, which can be associated
      with a state of consumptive coagulopathy (disseminated intravascular coagulation,
      DIC). Efforts being made to overcome antibody-mediated rejection include
      depletion of antibody by extracorporeal immunoadsorption, prevention of an
      induced antibody response by co-stimulatory blockade, B-cell and/or plasma cell
      depletion, depletion or inhibition of complement, or the use of organs from pigs
      transgenic for a human complement regulatory protein, such as hDAF. The ultimate
      solution would be the induction of both B- and T-cell tolerance to the
      transplanted pig organ, which is being explored by attempting to induce
      haematopoietic cell chimerism. One complication of this is a thrombotic
      microangiopathy, similar to thrombotic thrombocytopenic purpura. The many and
      diverse roles in which pharmacotherapy is involved in attempts to overcome the
      barriers of xenotransplantation are reviewed and current progress, particularly
      in our own laboratory, is discussed.

PMID- 11249513
TI  - Colorectal cancer staging and adjuvant chemotherapy.
AB  - Colorectal cancer is a significant cause of morbidity and mortality in Western
      populations. The standard of care for staging patients with colorectal cancer to
      determine prognosis and identify patients who will receive adjuvant therapy
      continues to be histopathology of regional lymph nodes. However, the significant
      variability in survival within each staging category likely reflects the
      heterogeneity of detecting micrometastatic disease employing this technique.
      Novel molecular markers of micrometastases currently in development will permit
      more accurate staging of patients with colorectal cancer. These advances in
      staging will distinguish patients who will maximally benefit from adjuvant
      therapy from those who have an especially good prognosis in whom chemotherapy can
      be avoided. In addition, new adjuvant chemotherapeutic agents, novel combinations
      of those agents and creative dosing schedules currently being investigated will
      offer considerable advantages with respect to ease of administration, safety and
      tolerability, quality of life and efficacy. Ultimately, it is anticipated that
      advances in molecular diagnostics will define unique biochemical characteristics
      of patients' tumours, permitting individualization of chemotherapeutic regimens
      employing novel agents that specifically exploit those characteristics.

PMID- 11249515
TI  - Reboxetine: the first selective noradrenaline re-uptake inhibitor.
AB  - Several treatment approaches are available for treatment of depression. However,
      reboxetine is the first selective noradrenaline re-uptake inhibitor. Whereas
      formerly only noradrenaline re-uptake inhibitors with a mixed mechanism of action
      were available. These included action not only at noradrenergic, but also at
      serotonergic and other neurotransmitter-sites. Thus, reboxetine represents the
      first of a new class of antidepressant agents with specificity for the
      noradrenergic system. Reboxetine has been shown to be an effective first-line
      treatment for patients with all grades of depression, to be effective in the
      prevention of relapse and recurrence and to offer significant benefits in terms
      of relieving the impaired social functioning associated with depressive
      disorders. Reboxetine was significantly superior to the serotonergic compound
      fluoxetine in improvement of social functioning in both the general depressed
      population and in those patients who achieved symptomatic remission, indicating a
      superior quality of remission. Altogether reboxetine was well tolerated during
      the acute and long-term treatment phase; side-effects such as increased sweating,
      constipation and dry mouth were the most prominent to be reported. The
      availability of reboxetine represents a significant addition to the currently
      available pharmacologic armamentarium for the treatment of depression.

PMID- 11249516
TI  - Review of quetiapine and its clinical applications in schizophrenia.
AB  - Preclinical studies have shown that quetiapine (Seroquel, AstraZeneca) is an
      atypical antipsychotic with many similarities to clozapine. Both placebo
      controlled and comparative studies in patients with schizophrenia have
      demonstrated that quetiapine has long-term efficacy in both positive and negative
      domains, as well as beneficial effects on affective and cognitive symptoms.
      Comparative clinical studies confirm that quetiapine is at least as effective as
      the standard antipsychotics, chlorpromazine and haloperidol and response rates
      with quetiapine are similar to those reported with other atypical antipychotics.
      Quetiapine has also demonstrated superior efficacy to haloperidol in partially
      responsive patients, who can be particularly difficult to treat. Quetiapine has a
      wide clinical dosing range (150-750 mg/day), although doses of 400 mg or above
      should be used in patients who do not fully respond to lower doses of the drug.
      Quetiapine is generally well tolerated with no requirement for routine ECG or
      blood monitoring and it has minimal effects on weight. Uniquely among other first
      line atypical antipsychotics, quetiapine is associated with a placebo-level
      incidence of EPS and an indistinguishable effect from placebo on plasma prolactin
      at all doses. Thus, clinicians can confidently increase the dose of quetiapine,
      without increasing the risk of EPS or hyperprolactinaemia. A number of studies
      have also shown that quetiapine is well-tolerated and effective in patients who
      are particularly susceptible to EPS, including elderly and adolescent patients
      and those with pre-existing dopaminergic pathology, such as Alzheimer's disease
      and Parkinson's disease. The consistent efficacy in treating all schizophrenic
      domains and good tolerability, particularly placebo-level EPS, make quetiapine
      acceptable to patients, as demonstrated in a survey of patient satisfaction. Thus
      quetiapine is a suitable first-line therapy for the treatment of schizophrenia
      and psychosis.

PMID- 11249517
TI  - Danaparoid sodium.
AB  - Danaparoid sodium (Orgaran, Organon) is a heparinoid glycosamino-glycuronan
      antithrombotic agent approved for the prophylaxis of post-operative deep vein
      thrombosis (DVT), which may lead to pulmonary embolism (PE) in patients
      undergoing elective hip replacement surgery. Danaparoid is a low molecular weight
      heparinoid consisting of a mixture of heparan sulphate (84%), dermatan sulphate
      (12%) and small amounts of chondroitin sulphate (4%), whose antithrombotic
      activity has been well established. Its pharmacological effect is exerted
      primarily by inhibiting Factors Xa (FXa) and IIa (FIIa) at a ratio greater than
      heparin, with a minimal effect on platelet function. Danaparoid exhibits low
      cross-reactivity with heparin-induced antibodies when compared with heparin or
      low molecular weight heparins (LMWH), thereby making it an excellent choice for
      the management of heparin-induced thrombocytopenia (HIT). It has excellent
      bioavailability following s.c. injection. Danaparoid has little effect on routine
      coagulation tests (activated partial thromboplastin time [aPTT], prothrombin time
      [PT], and thrombin time [TT]). Patients with elevated serum creatinine should be
      monitored carefully. For its FDA approved indication (DVT prophylaxis during hip
      replacement surgery), its cost per day is approximately eight times more than
      LMWH. Even though monitoring is not routinely necessary according to the
      manufacturer for its approved indication, monitoring is frequently necessary when
      it is used in other clinical scenarios. Its higher cost than comparable therapies
      for DVT prophylaxis and the low availability of the FXa assay in most non
      tertiary care hospitals has limited the widespread use of danaparoid. Danaparoid
      has been found to be effective in the treatment of HIT although this is an off
      label use, despite being the most frequent reason why danaparoid is used.

PMID- 11249518
TI  - The evolving pharmacotherapeutic profile of brimonidine, an alpha 2-adrenergic
      agonist, after four years of continuous use.
AB  - Since its introduction in 1996, use of brimonidine tartrate 0.2% ophthalmic
      solution (Alphagan, Allergan), a highly selective alpha 2-adrenergic agonist, has
      become increasingly popular for the initial and long-term management of ocular
      hypertension and glaucoma. Recently, ongoing clinical comparison trials of up to
      three years in length have reported sustained intraocular pressure (IOP) lowering
      efficacy with brimonidine 0.2% b.i.d., which was comparable with timolol 0.5%
      (Timoptic; Merck & Co.), accompanied by a favourable tolerability and safety
      profile. Also, many post-market studies have demonstrated the utility of
      brimonidine 0.2% b.i.d. as mono- and adjunctive therapy. Furthermore, major
      inroads have been made in the study of other possible pharmacotherapeutic
      benefits of brimonidine treatment, namely the potential for neuroprotection. This
      review will present a brief developmental history and examine key
      pharmacotherapeutic characteristics of brimonidine, including its receptor
      selectivity, IOP-lowering mechanism of action and potential neuroprotective
      activities. Moreover, the literature on brimonidine's efficacy and safety
      profiles in the treatment of ocular hypertension and glaucoma will be perused,
      and new four-year data from an ongoing double-masked clinical study comparing
      brimonidine tartrate 0.2% with timolol 0.5%, b.i.d. will be introduced.
      Brimonidine 0.2% b.i.d. provided sustained IOP-lowering efficacy comparable to
      timolol 0.5% b.i.d., with no significant differences at trough or peak during
      year four of continuous use. Visual fields were well preserved in both treatment
      groups with 93% of brimonidine patients and 91% of timolol patients showing no
      change or improvement. Brimonidine continued to appear safe and well-tolerated,
      with no clinically significant effects on mean heart rate or blood pressure, and
      no serious drug-related adverse events (AEs). Two out of 36 brimonidine patients
      developed ocular allergy; both were resolved without sequelae. Overall post
      market surveillance found no reports of unexpected or serious drug-related AEs.
      These long-term results, in conjunction with those reported in the literature,
      suggest that brimonidine 0.2% b.i.d. is a highly appropriate first- and second
      line therapy for long-term management of glaucoma and ocular hypertension.
      Potential neuroprotective effects of brimonidine therapy, which might provide
      additional vision sparing benefit, although supported by compelling animal
      studies, await clinical verification.

PMID- 11249519
TI  - Midodrine: a selective alpha-adrenergic agonist for orthostatic hypotension and
      dialysis hypotension.
AB  - Midodrine is an oral agent which acts as a selective peripherally-acting alpha
      receptor agonist. Midodrine is a prodrug that is almost completely absorbed after
      oral administration and converted into its active drug de-glymidodrine in the
      systematic circulation, with a bioavailability of 93%. It has been used
      successfully in the treatment of neurogenic orthostatic hypotension and more
      recently, in the treatment of dialysis hypotension. It acts through
      vasoconstriction of the arterioles and the venous capacitance vessels, thereby
      increasing peripheral vascular resistance and augmenting venous return,
      respectively. It is a unique agent in the armamentarium against orthostatic
      hypotension since it has minimal cardiac and CNS effects. This article will
      review the literature on midodrine for conditions of autonomic dysfunction, with
      focus on recent studies on its use in haemodialysis patients.

PMID- 11249520
TI  - Orlistat in the treatment of obesity.
AB  - Orlistat (Xenical, Hoffmann-La Roche) is a powerful inhibitor of gastrointestinal
      lipase and as such, reduces fat absorption. Unlike other weight-reducing drugs it
      is minimally absorbed and has no effects in the CNS. Orlistat is indicated for
      patients with a body mass index (BMI) of at least 30 kg/m2 or 28 kg/m2 in the
      presence of obesity-associated complications, such as hypertension, diabetes
      mellitus, hyperlipidaemia and obstructive sleep apnoea. In clinical trials,
      orlistat (120 mg t.i.d.) in combination with life-style modification and a
      hypocaloric diet (30% of energy from fat) induced significantly more weight loss
      and improved health complications of obesity (diabetes, hypertension,
      hyperlipidaemia) compared to patients treated with diet alone. Side effects
      related to fat malabsorption, occurred in more than 20% of subjects during the
      first year of treatment and included oily faecal spotting, abdominal pain, flatus
      with discharge and fatty/oily stool. Side effects from orlistat diminished in the
      second year of treatment. Plasma concentrations of fat soluble vitamins decreased
      in orlistat-treated patients but did not usually fall below the normal range. No
      studies have evaluated the efficacy of orlistat or side effect profile beyond two
      years.

PMID- 11249521
TI  - Thalidomide: a remarkable comeback.
AB  - The thalidomide product is a racemic mixture of the L- and D-enantiomeric forms
      of a synthetic glutamic acid derivative that contains a phthalimide ring and a
      glutarimide ring. Initially marketed as a sedative, it was withdrawan from the
      world market after it was found to be associated with severe birth defects.
      Recently, the compound has generated renewed interest because of its
      immunomodulatory and anti-angiogenic properties. The nature of its immunologic
      effects is under active investigation. It is orally bioavailable and can be
      administered in once daily dosing. Its primary route of metabolism is spontaneous
      hydrolysis. In controlled clinical trials, thalidomide has proven effective in
      the treatment of erythema nodosum leprosum, oral and oesophageal aphthous
      ulceration associated with advanced HIV infection and oral ulceration associated
      with Behcet's syndrome. Promising results have been obtained in preliminary
      studies of other immunologic and neoplastic disorders, but controlled clinical
      studies are still lacking for these entities. Adverse effects include
      teratogenicity, peripheral neuropathy and sedation. In the US, thalidomide can be
      prescribed only through a restricted drug distribution program.

PMID- 11249522
TI  - Emerging infectious diseases--a therapeutic challenge.

PMID- 11249523
TI  - Influenza.
AB  - The currently available antiviral drugs rimantadine and amantadine are effective
      only for influenza A viruses. Another class of influenza antiviral drugs is the
      neuraminidase inhibitors, which selectively inhibit both influenza A and B
      viruses. Recent studies have found the neuraminidase inhibitors zanamivir and
      oseltamivir to be 67-82% effective in preventing laboratory-confirmed infection
      when administered as prophylaxis during the influenza season. As treatment, they
      reduce the duration of illness by 1-1.5 days when started within 36-48 h of
      illness onset. The reported adverse effects of these drugs are minimal, and
      unlike amantadine and rimantadine, the drugs do not appear to affect the central
      nervous system. Poor oral bioavailability and rapid renal clearance limit the use
      of zanamivir to inhalation and concern has been raised about its use in
      asthmatics. The sialic acid analogue, GS4071, has been shown to be a potent
      inhibitor of neuraminidase activity and is shown to be effective in controlling
      influenza, and its prodrug form--GS4104 (oseltamivir) can be given orally. Direct
      comparison of zanamivir and oseltamivir, their use for prophylaxis and treatment
      in high-risk groups, and evaluation of their cost effectiveness are all required
      before they enter routine clinical practice.

PMID- 11249524
TI  - Weight gain associated with psychotropic drugs.
AB  - Weight gain is a common adverse effect of psychotropic drugs. Clinically
      significant weight gain puts the patient at risk for coronary heart disease,
      hypertension, Type II diabetes, dyslipidaemia and cancer, and can lead to non
      compliance, with the probability of relapse and subsequent (re)hospitalization.
      This review focuses on specific drug classes such as antipsychotics,
      antidepressants, mood stabilizers and anxiolytics that have a propensity to
      induce clinically significant weight gain. Patients should be informed of
      potential drug-induced weight gain and instructed in the importance of weight
      management techniques (e.g., proper nutrition, physical exercise, behaviour
      modification). Individual patient-risk profiles should also be assessed. To
      ensure adherence to treatment, a proactive physician-patient relationship is
      essential. Patient compliance and quality-of-life issues are addressed. For
      appropriate medication selection, the clinician should consider the weight gain
      potential of various psychotropic agents.

PMID- 11249525
TI  - Migraine pharmacotherapy with oral triptans: a rational approach to clinical
      management.
AB  - The recent clinical development of a number of migraine specific 5-HT1B/1D
      agonist triptans with enhanced lipophilicity (TELs), relative to the first drug
      of this class sumatriptan, and with a range of different metabolic,
      pharmacokinetic and receptor affinity profiles, provides the potential for
      critically different clinical profiles. Eletriptan, naratriptan, rizatriptan and
      zolmitriptan display both increased stability to first pass metabolic
      inactivation by monoamine oxidase (MAO-A) and enhanced lipophilicity (4- to > 120
      fold more than sumatriptan), leading to increased oral bioavailability (2- to 5
      fold more than the 14% reported for oral sumatriptan). Central penetration and
      increased receptor affinity and selectivity for the neuronal (5-HT1D) receptor
      also combine to allow for lower total oral dosing (i.e., unit doses of 15 mg or
      less compared with 50-300 mg doses of sumatriptan) and reduced peripheral
      exposure to the coronary vasoconstrictor (5-HT1B) receptor. The notable exception
      being eletriptan, where an active P-glycoprotein blood-brain barrier efflux
      system effectively negates these benefits and requires an 80 mg oral dose.
      Differences in the metabolic balance between hepatic P450 (especially CYP 1A2)
      and MAO-A inactivation lead to potential drug interactions for all TELs with the
      oral contraceptive pill (OCP), fluvoxamine and the quinilone antibiotics (with
      increased triptan levels). An important but complex MAO-A interaction between a
      metabolite of propranolol and rizatriptan mandates dosage reduction (to 5 mg) for
      rizatriptan in the presence of propranolol treatment. There is also an absolute
      contraindication for the concurrent administration of the MAO-A inhibitor
      moclobemide and rizatriptan. All the new-marketed TELs have potential clinical
      benefits and were well-tolerated relative to sumatriptan. Both rizatriptan (10
      mg) and zolmitriptan (2.5 mg and 5 mg) demonstrate at least equivalent efficacy
      to sumatriptan 25, 50 and 100 mg, respectively, making them suitable first line
      agents for moderate or severe migraine headaches. Rizatriptan has the fastest
      onset of effect of the TELs. Naratriptan would appear to have lower recurrent
      headache rate than sumatriptan, rizatriptan or zolmitriptan. Therefore, for
      headaches of long duration and with a tendency to recur naratriptan may be the
      most appropriate treatment. Thus, knowledge of the metabolic, pharmacokinetic and
      clinical profiles of the TELs facilitates the selection of a triptan which allows
      optimisation of the clinical benefits for individual patients, minimising the
      risk of drug interactions and a minimally effective dose to reduce potential
      adverse events (AEs).

PMID- 11249526
TI  - Modern adjunctive pharmacotherapy of myocardial infarction.
AB  - During acute myocardial infarction (MI), aspirin, beta-adrenergic antagonists and
      oral angiotensin converting enzyme (ACE) inhibitors should be used as an adjunct
      to reperfusion therapy. Medications upon discharge from the hospital should
      include aspirin and a beta-blocker. An ACE inhibitor should also be prescribed
      unless the ejection fraction is > 45%. Particular indications for an ACE
      inhibitor are an anterior MI, congestive heart failure, ejection fraction < 45%
      and mitral regurgitation. beta-blockers, when given to patients treated with ACE
      inhibitors, appear to produce an additional benefit compared with an ACE
      inhibitor alone. Based on the Scandinavian Simvastatin Survival Study (4S),
      Cholesterol and Recurrent Events (CARE) and Long-Term Intervention with
      Pravastatin in Ischemic Disease (LIPID) trials, a statin should also be given to
      subjects with low density lipoprotein (LDL)-cholesterol levels above 125 mg/dl,
      independent of total cholesterol levels. Therapy should be administered in an
      attempt to reduce the LDL-cholesterol level to 90-100 mg/dl (2.3-2.6 mM/l). In
      patients with normal or low levels on initial evaluation, screening for lipid
      abnormalities should be deferred for 2 months since acute phase responses and
      passive hepatic congestion can cause spuriously normal levels. Calcium channel
      blockers, nitrates, lidocaine, anti-arrhythmic drugs and i.v. magnesium should
      not be administered routinely after acute MI and their use should be restricted
      to selected settings.

PMID- 11249527
TI  - Platelet glycoprotein IIb/IIIa receptor antagonists.
AB  - The molecular understanding of platelet function, together with an appreciation
      of the role of platelet thrombus in the pathogenesis of acute coronary syndromes
      (ACS) and abrupt vessel closure following coronary intervention, lead to the
      development of the class of agents now referred to as platelet glycoprotein
      IIb/IIIa (GP IIb/IIIa) inhibitors. Currently three parenteral GP IIb/IIIa
      inhibitors are licensed for use in patients undergoing coronary intervention or
      as empirical therapy in non-ST elevation ACS (unstable angina and non-Q wave
      myocardial infarction). Clinical trials using these agents in patients undergoing
      coronary interventions have demonstrated a consistent reduction in ischaemic end
      points at 30 days that is sustained during long-term follow-up. Similar benefits
      have been found in patients with ACS who are managed medically or who proceed to
      revacularization. Studies using prolonged platelet inhibition using oral GP
      IIb/IIIa inhibitors in patients following coronary intervention or with ACS have
      produced disappointing results. Further investigation with existing and newer
      oral agents are ongoing. The use of GP IIb/IIIa inhibitors in combination with
      fibrinolytic agents for optimal reperfusion in patients with acute ST-elevation
      myocardial infarction (MI) is an active area of interest. Angiographic outcomes
      with this approach have been encouraging and clinical outcome data are awaited.
      Beyond efficacy, GP IIb/IIIa inhibitors have proven to be safe for clinical use.
      Haemorrhagic complications and thrombocytopenia are the most common adverse
      events, though infrequent. Unresolved issues regarding drug dosing, monitoring of
      effect, duration of therapy, head-to-head comparisons of agents, and use of
      adjunctive therapies are the subject of ongoing studies.

PMID- 11249528
TI  - Pharmacology for renal calculi.
AB  - Stone disease is as old as recorded history but despite advances in diagnosis and
      treatment, it continues to cause significant morbidity. This review summarises
      the current pharmacologic management of urinary calculi based upon the stone
      type. All patients with stone disease are advised to increase fluid intake, limit
      dietary protein and limit sodium. Calcium oxalate stones can be managed on a
      selective or non-selective basis depending on the cause of the hypercalciuria or
      hyperoxaluria. Agents currently in use include sodium cellulose phosphate,
      thiazides, orthophosphates, oral calcium supplements, pyridoxine, cholestyramine,
      citrate, magnesium and allopurinol. Classically, struvite stones occur in the
      presence of urea splitting organisms and are composed of magnesium, ammonium
      phosphate and carbonate apatite. The goal of treatment is to make patients stone
      free as bacteria retained in stone fragments lead to stone growth. Urease
      inhibitors, aluminium hydroxide gel, hemiacidrin, and Suby G and M solutions are
      infrequently used in treatment. Cystine stones are the result of an autosomal
      recessive disorder. D-Penicillamine, captopril and alpha-mercaptopropionylglycine
      (MPG) are all oral agents that have proven to be efficacious. As more randomised
      trials are conducted and the understanding of endogenous stone inhibitors
      progresses, the medical management of stone disease will continue to improve.

PMID- 11249529
TI  - Non-steroidal anti-androgens in prostate cancer--current treatment practice.
AB  - Adenocarcinoma of the prostate is a common disease that causes significant
      morbidity and mortality in the adult male population. Hormonal therapy for
      prostate cancer is considered when a patient fails with initial curative therapy,
      such as radical prostatectomy or definitive radiation therapy, or if he is found
      with an advanced disease. Many hormonal agents have been developed to exploit the
      fact that prostate cancer growth is dependent on androgen. Non-steroidal anti
      androgens (NSAAs) block androgen at the cellular level. Numerous clinical trials
      comparing monotherapy of castration and combination therapy of castration and
      NSAAs have been performed. At present, the results of the trials with regard to
      the survival of patients under therapy are conflicting. When the disease recurs
      in a patient in the middle of combination androgen blockade therapy, androgen
      withdrawal should be considered. The benefits of NSAA in monotherapy,
      intermittent or neoadjuvant therapy are not clear at present. Better designed,
      larger cohort clinical trial may be necessary to clarify the confusion.

PMID- 11249530
TI  - Treatment advances in non-Hodgkin's lymphoma.
AB  - Non-Hodgkin's lymphomas (NHL) encompass a heterogeneous group of lymphoid
      malignancies with varying natural histories and prognoses. Recent classifications
      for NHL have defined distinct lymphoma entities based on morphology,
      immunophenotype, genetic features, clonal cell lineage and clinical features.
      These new, more precise classifications and characterizations of NHL will be
      essential in developing new targeted therapies. However, for this brief review,
      we will continue describe NHL primarily as indolent or aggressive. Treatment
      options for patients with indolent, but generally incurable, lymphomas include a
      'watch and wait' approach, single agent alkylators, nucleoside analogues,
      combination chemotherapy, immunotherapy with monoclonal antibodies, radiolabelled
      monoclonal antibodies, or interferon (IFN). Vaccine therapy for indolent
      lymphomas is currently under intense investigation. For aggressive lymphomas,
      combination chemotherapy remains the standard of care. Major advances in the
      management of aggressive lymphomas include validation of the international
      prognostic index and clarification of the role of high-dose therapy with bone
      marrow or stem cell transplant in patients with relapsed aggressive lymphomas.
      Multiple randomised pilot trials of high dose therapy as initial therapy for
      aggressive lymphomas have shown conflicting results and await confirmatory
      studies.

PMID- 11249531
TI  - Butenafine hydrochloride: for the treatment of interdigital tinea pedis.
AB  - Butenafine, a derivative of benzylamine with potent fungicidal activity is a new
      generation of antimycotic compound that has shown to be extremely effective
      against experimentally-induced tinea pedis in the guinea-pig, a situation that
      resembles synergetic pathology similar to that of tinea pedis in humans.
      Butenafine, (N-4-tert-butylbenzyl-N-methyl-1-naphthalenemethyl-amine
      hydrochloride) with a chemical structure and mode of action similar to those of
      the allylamines, demonstrates superior fungicidal activity in vitro against
      dermatophytes and superior fungistatic activity toward Candida albicans that of
      naftifine and terbinafine. In vitro, pharmacodynamic data has shown that the
      geometric mean of minimum inhibitory concentration values for butenafine were
      comparatively lower than those of naftifine and clotrimazole against clinical
      isolates for many dermatophytes. It inhibits sterol synthesis by blocking the
      squalene epoxidation stage in fungi. In phramacokinetic assessments butenafine
      achieves and maintains high concentrations and long retention time in skin, with
      associated anti-inflammatory activity in vivo. In controlled clinical trials when
      applied topically, butenafine appears to be well tolerated with a subjective mild
      burning sensation at the application site. There were no withdrawals from the
      study. Butenafine is sparingly soluble in water but readily soluble in methanol,
      ethanol, dichloromethane and chloroform. If incorporated properly in semisolid
      topical preparations, with a balanced vehicle, butenafine hydrochloride
      potentially exhibits as a promising alternative antimycotic agent for the
      treatment of tinea pedis.

PMID- 11249532
TI  - Amphotericin B colloidal dispersion.
AB  - Amphotericin B colloidal dispersion (ABCD) is a colloidal dispersion of a stable
      complex of amphotericin B with cholesteryl sulphate in a 1:1 proportion, forming
      uniform disk-shaped particles. ABCD is associated with less nephrotoxicity than
      conventional amphotericin B deoxycholate. Infusion-related adverse events are
      more frequent in patients receiving ABCD than in patients receiving liposomal
      amphotericin B or amphotericin B deoxycholate. ABCD has been shown in a
      randomised, double-blind study, to be an effective alternative to amphotericin B
      deoxycholate for empirical treatment of patients with fever and neutropenia. ABCD
      is active in the treatment of invasive Candida spp. and Aspergillus spp.
      infections in immunocompromised hosts, however most of the data supporting its
      use for these types of infections is derived from non-comparative open-label
      clinical trials of patient refractory to or intolerant of conventional antifungal
      therapy. ABCD is approved by the US FDA for the treatment of invasive
      aspergillosis in patients where renal impairment of unacceptable toxicity
      precludes the use of amphotericin B deoxycholate in effective doses, and in
      patients with invasive aspergillosis where prior amphotericin B deoxycholate
      therapy has failed. Two other lipid formulations of amphotericin B, amphotericin
      B lipid complex and liposomal amphotericin B, are available and, like ABCD, are
      associated with reduced nephrotoxicity as compared to amphotericin B
      deoxycholate. The role of ABCD in comparison with these other lipid formulations
      of amphotericin B is discussed herein. High cost remains an issue with all lipid
      formulations of amphotericin B.

PMID- 11249533
TI  - Azithromycin: indications for the future?
AB  - The global challenge of optimally treating bacterial infections is continuously
      evolving. Azithromycin, the first azalide antibiotic, presents pharmacokinetics
      and pharmacodynamics that allow for a simple dosing regimen with minimal side
      effects. Current azithromycin uses include a variety of community-acquired
      respiratory tract, skin and soft tissue, and sexually transmitted disease
      infections. Azithromycin has also demonstrated substantial activity against
      atypical organisms such as Mycobacterium avium complex (MAC) and Chlamydia
      trachomatis. Due to a never-ending need for new antibiotic therapies, several
      other potential indications for azithromycin are being researched. This article
      will present various current research associated with azithromycin's potential
      use for malaria, trachoma, coronary artery disease (CAD), Pseudomonas aeruginosa
      infections, erythema migrans, short-term therapy for respiratory infections,
      typhoid, cryptosporidiosis, pelvic inflammatory disease, acne, Mediterranean
      spotted fever and MAC. As bacterial and parasite resistance patterns fluctuate
      globally, azithromycin may be an alternative therapy for the previously mentioned
      indications, which will also enhance patient compliance and therefore effectively
      eradicate infection worldwide.

PMID- 11249534
TI  - Clarithromycin for Helicobacter pylori infection.
AB  - Helicobacter pylori, a Gram-negative organism that survives in the deep mucus
      layer and attaches to the gastric surface cells, is estimated to be present in up
      to one-half of the US population. Chronic H. pylori infection causes chronic
      gastritis, peptic ulcer diseases and even gastric cancer. Cure of the infection
      leads to healing of gastric inflammation, prevention of development of peptic
      ulcer, as well as accelerated healing of peptic ulcers, and prevention of ulcer
      recurrence. Treatment of H. pylori has undergone substantial evolution over the
      past decade. Despite the in vitro susceptibility, results from single or even
      dual drug therapy is typically unsatisfactory and the best therapy is yet to be
      defined. The best current therapies for H. pylori infection consist of a proton
      pump inhibitor (PPI) or ranitidine bismuth citrate and two antibiotics (triple
      therapies), or bismuth, tetracycline, metronidazole and a PPI (quadruple
      therapy). Clarithromycin is one of the most useful antimicrobials against H.
      pylori. It is an acid-stable macrolide with a broad spectrum of antibacterial
      activity, well absorbed with a wide tissue distribution and with mild side
      effects. Clarithromycin has a low minimum inhibitory concentration (MIC50) for H.
      pylori and its effect is potentiated by acid inhibition. When combined with a PPI
      or ranitidine bismuth citrate and amoxicillin or metronidazole, eradication rates
      of more than 95% can be achieved with susceptible organisms. However, the
      prevalence of primary and acquired clarithromycin resistance, which is due to
      mutations within a conserved loop of 23S rRNA of H. pylori, is increasing. In
      practice, the presence of clarithromycin resistance usually implies reduced
      success when clarithromycin-containing regimes are used. There is a need for
      improved therapies for H. pylori where antibiotic resistance is less of a
      problem.

PMID- 11249536
TI  - Anagrelide: a novel agent for the treatment of myeloproliferative disorders.
AB  - Anagrelide hydrochloride (Agrylin, Roberts Pharmaceutical Corp.) is an oral
      imidazoquinazoline agent that has been shown to reduce elevated platelet counts
      and the risk of thrombosis in patients with thrombocythaemia in various
      myeloproliferative disorders (MPD). It is currently approved by the FDA as oral
      treatment for essential thrombocythaemia (ET) and thrombocythaemia associated
      with polycythaemia vera (PV). Anagrelide selectively suppresses bone marrow
      megakaryocytes by interfering with the maturation process and decreasing platelet
      production without affecting the erythroid and myeloid progenitor cells. Other
      medications indicated for the treatment of thrombocythaemia, including interferon
      alpha (IFN-alpha), alkylating agents and hydroxyurea, suppress all cell lines.
      Anagrelide is known to inhibit platelet cyclic adenosine monophosphate (cAMP)
      phosphodiesterase at concentrations that exceed those achieved at doses used to
      treat ET. Anagrelide is extensively metabolised in the liver and its metabolites
      are primarily excreted in the urine. Adverse effects associated with the use of
      anagrelide are primarily caused by the drugs' direct vasodilating and positive
      inotropic effects. These include headache, hypotension and diarrhoea. It has also
      been known to cause fluid retention, tachycardia, nausea, abdominal pain and
      arrhythmias. The starting dose of anagrelide ranges from 0.5 mg q.i.d. to 1 mg
      b.i.d. with a maximum dose of 2.5 mg q.i.d. Adequate responses have been
      maintained with a median dose of 2-2.5 mg/day. Platelet counts begin to decrease
      in 7-10 days, however, they return to pre-treatment levels within 4-8 days if
      therapy is stopped. Anagrelide 2 mg/day for one year costs approximately US$6439,
      and treatment must continue indefinitely [1].

PMID- 11249535
TI  - The fixed combination of verapamil SR/trandolapril.
AB  - Fixed verapamil SR/trandolapril combinations 180/1 mg and 180/2 mg (Tarka, Knoll
      AG) have a significantly superior antihypertensive effect compared to equal
      dosages of either agent alone. Verapamil SR/trandolapril 180/2 mg combination
      produces the best dose-response ratio of different dose combinations of these two
      drugs. Combination therapy has the most pronounced effect on blunting the early
      morning rise in blood pressure. Thus, verapamil SR/trandolapril combination
      therapy may be an appropriate treatment option in patients with moderate
      essential hypertension, particularly in those who have a tendency toward the
      early morning rise in blood pressure. The adverse effect profile of the fixed
      combination of verapamil SR/trandolapril includes the typical side effects of its
      monocompounds. The fixed combination of verapamil SR/trandolapril is also
      effective and safe in the treatment of hypertension in the elderly. The fixed low
      dose combination therapy with verapamil SR/trandolapril 180/2 mg is a suitable
      treatment option for patients with moderate essential hypertension and Type 2
      diabetes mellitus, because it improves parameters of carbohydrate metabolism and
      uricaemia and does not alter the lipid profile. The insulin-sensitising effect of
      angiotensin converting enzyme (ACE) inhibitor monotherapy with its theoretical
      risk of hypoglycaemia is completely neutralised in the combination with verapamil
      SR. Comparative studies have shown that the low-dose combination of verapamil
      SR/trandolapril may be a suitable alternative to combinations containing a
      thiazide diuretic or a beta-blocking agent for the long-term management of
      hypertensive patients for whom combination therapy is indicated. The combination
      of an ACE inhibitor with a non-dihydropyridine calcium channel blocker reduces
      proteinuria to a greater extent than either agent alone. A combination of an ACE
      inhibitor and a calcium channel blocker may provide additional benefit in
      inducing the regression of left ventricular hypertrophy. Combination therapy
      leads to a significant increase in left ventricular ejection fraction,
      improvement of wall motion index and increases exercise duration time in patients
      with coronary heart disease and left heart failure. It also improves the ratio of
      exercise to rest rate-pressure product and decreases the number of angina
      attacks. These findings support the hypothesis that the combination of verapamil
      and trandolapril might be useful in patients with attenuated left ventricular
      function and angina pectoris. Thus, Tarka is an effective and well-tolerated
      antihypertensive agent with a good safety profile and positive metabolic effects.

PMID- 11249537
TI  - Gemcitabine in the treatment of bladder cancer.
AB  - New agents are available for the treatment of metastatic transitional cell
      carcinoma of the bladder. In the US, the combination of methotrexate,
      vinblastine, doxorubicin and cisplatin (M-VAC) remains the standard chemotherapy
      regimen for advanced bladder cancer. Gemcitabine (2',2'-difluorodeoxycytidine
      [dFdC]) is a relatively new agent with a favourable toxicity profile that has
      demonstrated activity against a number of solid tumours in both preclinical and
      clinical studies. Single-agent gemcitabine has shown activity in bladder cancer
      in both pretreated and chemotherapy-naive patients. The combination of
      gemcitabine plus cisplatin is a regimen with significant activity and moderate
      toxicity in bladder cancer patients. A randomised trial of gemcitabine plus
      cisplatin versus M-VAC has completed accrual but has not yet been reported. New
      combination studies of gemcitabine with other chemotherapy agents, including the
      taxanes, are ongoing.

PMID- 11249538
TI  - Cabergoline.
AB  - Cabergoline (CAB) (1-[(6-allelylergolin-8 beta-yl)carbonyl]-1-[3
      (dimethylamino)propyl]-3-ethyl-urea) is an ergoline derivative with potent,
      selective and long-lasting inhibitory activity on prolactin (PRL) secretion
      acting on dopamine receptors present in pituitary lactotrophes. Receptor binding
      studies have demonstrated that CAB has high in vitro selectivity and affinity for
      the subtype D2 of the dopamine receptor. In cultures of rat anterior pituitary
      cells, the concentrations of CAB and bromocriptine required to inhibit PRL
      secretory activity by 50% (IC50) were 0.1 and 3.4 nmol/l, respectively. As
      compared to bromocriptine, CAB was more potent in inhibiting the binding of [3H]N
      n-propylnorapomorphine and it occupied the receptor for longer. These effects
      were observed in all areas of the rat brain. In vivo, CAB at doses of 0.125-1 mg
      twice weekly caused a dose-dependent suppression of PRL secretion in women with
      hyperprolactinaemia. CAB was shown to be significantly more effective than
      bromocriptine in inducing a complete biochemical response and clinical efficacy
      and was better tolerated than bromocriptine in the majority of patients. Notable
      tumour shrinkage until tumour disappearance was observed during CAB treatment in
      most patients with macroprolactinoma. CAB was also shown to be effective in
      patients resistant or poorly responsive to bromocriptine. In view of the limited
      data on CAB-associated pregnancies and the long half-life of the drug, it is
      currently recommended that women seeking to became pregnant, once ovulatory
      cycles have been established, should discontinue CAB therapy 1 month before they
      intend to conceive. However, no data on negative effects on pregnancy or
      offspring have been reported. The great efficacy of CAB together with its
      excellent tolerability makes this drug the current treatment of choice for the
      majority of patients with hyperprolactinaemic disorders. Very recently, the
      efficacy of CAB treatment has been reported in patients with acromegaly and
      clinically non-functioning adenomas with controversial results. CAB was also
      reported to have some efficacy in patients with Nelson's syndrome and Cushing's
      disease although these data are available only for limited case reports.

PMID- 11249539
TI  - The Sixth International Conference on Endothelin. October 1999, Montreal, Canada.
AB  - Since its discovery in 1988, there has been an enormous amount of interest in
      endothelin-1 (ET-1) and its regulatory and growth-promoting role in
      cardiovascular physiology. Evidence from the Sixth International Conference on
      Endothelin, held in Montreal in October 1999, continued to demonstrate that the
      endothelin system is an important therapeutic target in cardiovascular disease,
      with promising results in animal studies now being confirmed by clinical trials
      in humans. In addition, many new and exciting roles for ET-1 were presented,
      suggesting that ET-1 antagonism may have a broader therapeutic potential than
      previously imagined.

PMID- 11249540
TI  - 72nd Meeting of the American Heart Association. November 1999, Atlanta, Georgia,
      USA.
AB  - The American Heart Association annual meeting must be one of the largest
      scientific gatherings, attracting over 30,000 delegates. The meeting at the end
      of last year was held in Atlanta, USA, the 2000 meeting will be in New Orleans,
      USA. The following highlights represent my own interests.

PMID- 11249541
TI  - The new antipsychotics--some pharmacological aspects of their problems and
      potential.
AB  - The drug treatment of schizophrenia still offers many challenges, despite the
      efficacy of the classical antipsychotics. Although the more recently introduced
      drugs demonstrate a diminished incidence of certain side effects, notably
      extrapyramidal motor symptoms, it is clear that they do not adequately address
      all symptoms of the disease. In addition, weight gain remains a major problem
      following treatment with many older and newer antipsychotic drugs. Nevertheless,
      some progress has been made towards ameliorating negative, depressive and
      cognitive features of schizophrenia. The newer antipsychotics show differential
      effects against these and other symptoms and thus their pharmacological profiles
      provide us with clues as to the receptor mechanisms underlying their therapeutic
      and side effects.

PMID- 11249542
TI  - Chemotherapy of breast cancer: are the taxanes going to change the natural
      history of breast cancer?
AB  - Among the novel chemotherapeutic drugs introduced in the last decade, taxanes
      have emerged as the most powerful compounds and results available to date suggest
      that they will be remembered in the future as the breast cancer chemotherapy of
      the 1990s. The two taxanes (paclitaxel, Taxol, Bristol-Myers Squibb and
      docetaxel, Taxotere, Rhone-Poulenc Rorer) share some characteristics, but are
      also significantly different both in preclinical profile and, most importantly,
      in clinical characteristics. The main clinical differences are related to their
      different efficacy-toxicity ratio in relation to dose and schedule; the differing
      integrability of paclitaxel and docetaxel in anthracycline-taxane containing
      regimens, secondary to major differences in pharmacokinetic interactions between
      each taxane and the anthracyclines, and; the potential differences in level of
      synergism between each taxane and herceptin (HeR2Neu antibody/trastuzumab,
      Genentech/Roche). In clinical practice, the taxanes are now standard therapy in
      metastatic breast cancer after prior chemotherapy, in particular anthracyclines,
      has failed. Their role in combination with anthracyclines in first-line therapy
      of advanced breast cancer is emerging and sheds new light on the potential role
      of taxanes in the adjuvant setting. However, the impact of taxanes on the natural
      history of breast cancer is yet to be defined, despite the trend of results
      suggesting that these agents have the potential for significant improvements in
      advanced and, most importantly, adjuvant therapy of breast cancer. The results of
      all completed or ongoing Phase III trials in first-line metastatic and the
      adjuvant setting will help determine if taxanes will further improve the outcome
      of breast cancer or not.

PMID- 11249543
TI  - Advances in use of the 5-HT3 receptor antagonists.
AB  - Nausea and vomiting continue to rank as important side effects for cancer
      patients receiving chemotherapy. The class of drugs known as the 5-HT3 receptor
      antagonists have become widely used for chemotherapy-induced nausea and vomiting,
      and are considered a standard part of care for moderately- and highly-emetogenic
      chemotherapy in combination with corticosteroids. Ondansetron (Zofran, Glaxo
      Wellcome), granisetron (Kytril, SmithKline Beecham) and dolasetron (Anzemet,
      Hoechst Marion Roussel) are commercially available in the US. Intravenous forms
      of all three drugs have demonstrated efficacy in preventing acute (< or = 24 h
      following chemotherapy) nausea and emesis due to moderately- and highly
      emetogenic chemotherapy. Oral forms of the drugs have been shown to be effective
      in prevention of nausea and emesis due to moderately-emetogenic chemotherapy.
      More recently, oral 5-HT3 receptor antagonists have demonstrated efficacy in the
      prevention of nausea and vomiting due to highly-emetogenic chemotherapy as well.
      Comparative trials between the three agents have shown no clinically important
      differences in outcome and they should be considered clinically equivalent.
      Optimal oral anti-emetic regimens for high-dose chemotherapy with bone marrow or
      stem cell transplantation remain to be determined and future oral studies should
      target this population. In general, the decision of which 5-HT3 receptor
      antagonist to select for formulary inclusion should be based on the dose of anti
      emetic used and the acquisition cost of the agents being compared. The oral route
      should be used whenever possible.

PMID- 11249544
TI  - Bisphosphonates in osteoporosis: recent clinical experience.
AB  - Bisphosphonates are potent inhibitors of bone resorption that have come to play a
      prominent role in the prevention and treatment of various forms of osteoporosis
      and other metabolic bone disorders. Therapy in women with osteoporosis and at
      high fracture risk substantially reduces the incidence of vertebral and non
      vertebral fractures. In younger postmenopausal women, bisphosphonates are
      attractive alternatives to oestrogen to prevent bone loss and the subsequent
      development of osteoporosis. Bisphosphonates have recently become the treatment
      of choice to prevent and treat the skeletal consequences of chronic
      corticosteroid therapy. When administered appropriately, these drugs are very
      well tolerated and have an excellent safety profile. The challenges now to
      clinicians are to identify the patients for whom bisphosphonate therapy is
      indicated and to devise dosing and monitoring strategies to enhance the long-term
      adherence to therapy required to realise the full benefits of these treatments.

PMID- 11249545
TI  - Current treatment options to prevent perinatal transmission of HIV.
AB  - Mother-to-infant transmission is the primary means by which young children become
      infected with HIV. WHO estimates approximately 1600 infants become infected with
      HIV every day. Recent advances in identifying the factors determining perinatal
      transmission have allowed interventions to be made to reduce mother-infant
      transmission. Paediatric AIDS Clinical Trials Group (PACTG) protocol 076, the
      pivotal vertical transmission study demonstrated that zidovudine (AZT) in
      pregnancy could reduce perinatal transmission of HIV-1 by 67%. This was confirmed
      by PACTG 185, in pregnant women with more advanced disease, which also
      demonstrated that viral load was the only independent factor determining vertical
      transmission rate (VTR). More recently, results from several short-course
      antiretroviral trials have brought new hope, that effective preventative
      interventions can be extended to developing countries. Although most studies have
      involved shorter versions of PACTG 076, the latest finding from HIVNET 012
      demonstrated a significant reduction in VTR using a two-dose regimen of
      nevirapine (NVP). This intervention is the simplest, least expensive regimen so
      far with proven efficacy in diminishing mother-infant transmission. Non
      pharmacological interventions have also been studied recently. The benefits of
      elective caesarean section (ELCS) have been clearly demonstrated in recent
      studies. These studies were carried out at a time when highly active antiviral
      therapies (HAART) were not available. There is still no information as to whether
      ELCS provides any added benefit for women on HAART with an undetectable HIV viral
      load. Prevention of breastfeeding can also further reduce VTR. This strategy is
      more applicable to resource-rich countries where access to formula feeds is not a
      problem. Options to prevent perinatal transmission must take into consideration
      the economic climate in which the intervention is to be made. In developed
      countries, effective intervention with perinatal AZT, ELCS and exclusive formula
      feeding has already reduced the VTR to around 1%. There is limited safety data
      currently available on the use of other antiretrovirals in pregnancy. A cautious
      approach to the use of HAART in pregnancy is recommended at present.

PMID- 11249546
TI  - The new atypical antipsychotics: a review of pharmacoeconomic studies.
AB  - The pharmacoeconomic evaluation of atypical antipsychotics for the treatment of
      schizophrenia involves documentation of clinical effectiveness, quality of life
      and medical cost outcomes. The findings of pharmacoeconomic studies assist
      psychiatrists and mental healthcare decision-makers in identifying therapies that
      provide the greatest benefit to patients at the most acceptable cost. The cost
      effectiveness of the newer atypical antipsychotics has been examined using non
      controlled cohort studies (either retrospective or prospective), modelling
      studies or randomised clinical trials. The evidence, from a variety of studies,
      indicates that clozapine is a cost-effective treatment for neuroleptic refractory
      schizophrenia. Risperidone and olanzapine may be cost neutral, or at best
      slightly cost saving, compared with conventional antipsychotics, although they do
      improve patient clinical effectiveness and quality of life outcomes. There is too
      little data on pharmacoeconomic outcomes for sertindole and quetiapine to make
      any conclusions about their cost-effectiveness in treating schizophrenia.

PMID- 11249547
TI  - New advances in the pharmacological management of chronic heart failure.
AB  - The management of heart failure has evolved in parallel with advances in the
      understanding of the disease process. Inotropes and diuretics are used to combat
      pump failure and fluid overload. While no convincing data has emerged regarding
      the long-term safety of inotropes, new exciting data concerning the role of
      diuretics, especially aldactone, has led to a renewed interest in this class of
      drug therapy. Angiotensin converting enzyme inhibitors (ACE inhibitors) were
      noted to not only affect symptomatology but also decrease mortality by
      interfering with the renin-angiotensin-aldosterone system. Recent research has
      focused on more complete blockade of the renin-angiotensin system than that
      achieved with ACE inhibitors alone with the addition of direct angiotensin II
      receptor blockers. This new class of drugs may become not only a reasonable
      alternative to ACE inhibitors in patients intolerant of the drug but also a
      possible addition to ACE inhibitors in the battle to prevent progression of
      remodelling and disease. beta-blockers are the most exciting new class of drugs
      used to combat heart failure. They appear not only to combat the remodelling
      process that occurs in the progression of disease but also other pathological
      events such as apoptosis and cellular oxidation. New medical therapies currently
      being investigated include novel agents such as endothelin antagonists,
      natriuretic peptides, vasopressin antagonists and anticytokine agents--all part
      of a new era in drug management of heart failure that has evolved with continued
      advances in the understanding of chronic heart failure (CHF).

PMID- 11249548
TI  - Etoposide in prostate cancer.
AB  - Hormone refractory prostate cancer is a disease that kills approximately 39,000
      people per year. No single chemotherapeutic agent or regimen has been
      demonstrated to provide a survival advantage in this disease. Etoposide as a
      single agent, both in i.v. and oral formulations has not proven to be effective.
      In the 1990s, however, etoposide has been combined with several agents to create
      novel treatment regiments for patients with hormone refractory disease. Several
      of these regimens, all involving oral etoposide, have demonstrated promising
      results in Phase II trials and early results suggest that they may increase
      survival for hormone refractory patients, although this remains to be tested in a
      Phase III trial setting.

PMID- 11249549
TI  - Nimesulide: an NSAID that preferentially inhibits COX-2, and has various unique
      pharmacological activities.
AB  - Nimesulide is a NSAID with good anti-inflammatory, analgesic and antipyretic
      activities expected of such compounds. However, in addition it has some unique
      therapeutic and pharmacological activities. The novel therapeutic aspects include
      a relatively low toxicity to the gastrointestinal tract and kidneys, it can be
      given to most patients who experience respiratory problems with other NSAIDs, and
      the onset of analgesia is comparatively quick. The main novel pharmacological
      actions obtained using nimesulide in vivo at therapeutic doses, or in vitro at
      concentrations within the therapeutic range of free (unbound) drug, include: a
      preferential inhibition of prostaglandin synthesis via COX-2, and reductions in
      cytokine action/release, histamine release, the release of enzymes that degrade
      cartilage, and the release of superoxide anions and other toxic substances from
      neutrophils. Interactions with other drugs are few and of little or no clinical
      significance.

PMID- 11249550
TI  - Itraconazole.
AB  - Itraconazole is a broad spectrum triazole antifungal agent. It has favourable
      pharmacodynamic and pharmacokinetic profiles and is available as both oral and
      i.v. formulations. Over the last two decades, clinical and animal infection
      studies have demonstrated the efficacy of itraconazole in a wide range of
      superficial fungal infections including difficult-to-treat dermatophytoses and
      onychomycoses. Furthermore, shortened treatment regimens have proven to be
      effective, ranging from 1-day treatment for vaginal candidosis to 1-week pulse
      therapy per month, for 2-4 months, in onychomycosis and follicular
      dermatophytosis. Clinical experience with itraconazole in the treatment of deep
      mycoses is less comprehensive. However, results in systemic candidosis,
      sporotrichosis, blastomycosis, paracoccidioiodomycosis, certain types of
      histoplasmosis and aspergillosis are extremely encouraging. Itraconazole is less
      effective in the treatment of chromomycosis and coccidioidomycosis. Nevertheless,
      considering the refractory nature of these diseases, itraconazole has proven to
      be a valuable addition to the antifungal drugs currently available for treatment.
      Itraconazole has been well-tolerated with doses of up to 400 mg/day being
      generally free of serious adverse effects. However, a potential for drug
      interactions exists, mediated through the cytochrome P450 enzyme 3A4 system,
      which should be considered when itraconazole is used as part of a multi-drug
      regimen.

PMID- 11249551
TI  - Olanzapine: an atypical antipsychotic for schizophrenia.
AB  - Olanzapine is a serotonin-dopamine receptor antagonist primarily used in the
      treatment of psychotic illnesses. It has been shown in numerous large trials to
      be as equally effective as haloperidol in the acute treatment and maintenance
      treatment of schizophrenia. However, olanzapine was shown to be more effective
      than haloperidol in the treatment of negative symptoms and to cause significantly
      fewer extrapyramidal symptoms. Furthermore, early reports suggest that olanzapine
      produces less tardive dyskinesia than haloperidol, though longer follow-up data
      are needed. Current studies have failed to demonstrate the efficacy of olanzapine
      in the treatment of refractory schizophrenia. One comparison trial of olanzapine
      versus risperidone has indicated similar efficacy. Clinical trials in acute mania
      have found olanzapine to be more effective than placebo. However, there is no
      role for olanzapine monotherapy in bipolar disorder given current studies.
      Although olanzapine has shown a low rate of extrapyramidal symptoms, it is not
      without adverse effects. Clinically significant weight gain has been noted with
      olanzapine in each of the large clinical trials. The degree of weight gain is
      similar to clozapine and probably greater than that observed with risperidone.
      The long-term medical consequence of atypical antipsychotic-induced weight gain
      is not known at this time. While generally considered first-line drugs from an
      efficacy and adverse effect standpoint, pharmacoeconomic studies are needed to
      justify the large acquisition cost of olanzapine compared to typical agents.

PMID- 11249552
TI  - Ropivacaine.
AB  - Ropivacaine (Naropin, AstraZeneca) is a long-acting amide local anaesthetic
      released for clinical use in 1996. Similar to bupivacaine, ropivacaine is equally
      effective for s.c. infiltration, epidural and peripheral nerve block for surgery,
      obstetric and post-operative analgesia. Ropivacaine differs from most other amide
      type local anaesthetics in that it is marketed as a pure S-enantiomer, instead of
      as a racemate. This feature improves the safety of ropivacaine, and, indeed,
      studies have shown ropivacaine to have less cardiovascular and CNS toxicity than
      bupivacaine. Ropivacaine is nearly identical to bupivacaine in onset, quality and
      duration of sensory block, but it produces less motor block. Whether or not the
      motor sparing effect of ropivacaine is due to a lower relative potency compared
      to bupivacaine is a matter of intense debate. Despite a better safety profile,
      the increased cost of ropivacaine may limit its clinical utility.

PMID- 11249553
TI  - Valsartan: a novel angiotensin type 1 receptor antagonist.
AB  - Valsartan is a highly selective, orally available antagonist of the angiotensin
      Type 1 (AT1) receptor. It is indicated for treatment of mild to moderate
      essential hypertension. Experimental studies have confirmed the abolition or
      attenuation of angiotensin II (AII)-related effects, such as vasoconstriction,
      cell growth promotion and aldosterone release. In humans, valsartan is rapidly
      absorbed with maximal plasma concentrations occurring 1-2 h after oral
      administration. The elimination half-life comes to about 7-8 h, valsartan is
      metabolised to a negligible extent and most of the drug is excreted via the
      faeces. There is no dose adjustment required for patients with a creatinine
      clearance > 10 ml/min. The dose should not exceed 80 mg o.d. in patients with
      hepatic dysfunction, valsartan is not recommended for patients with severe
      hepatic dysfunction and/or biliary cirrhosis. At present, no clinically relevant
      pharmacokinetic drug interactions have been observed. Valsartan produces
      persistent blood pressure reductions in patients with mild to moderate
      hypertension, the recommended starting dose is 80 mg o.d. If required, the dose
      may either be increased to 160 mg o.d. or hydrochlorothiazide may be added. In
      comparison to other antihypertensive drugs valsartan therapy leads to similar
      blood pressure reductions, while exhibiting a favourable tolerability profile.
      Preliminary studies suggest beneficial effects in patients with hypertensive end
      organ damage such as renal disease and left ventricular hypertrophy. Furthermore,
      the drug is evaluated for its efficacy in heart failure and patients post
      myocardial infarction.

PMID- 11249554
TI  - Levofloxacin.
AB  - Levofloxacin (DR-3355, Daiichi) is a new fluoroquinolone antibiotic which is the
      active isomer of ofloxacin (DL-8280, Daiichi). By removing the inactive isomer,
      the in vitro activity of levofloxacin is 8-128 times higher than that of
      ofloxacin. This means that bacterial species, which have borderline
      susceptibility to ofloxacin and other first generation fluoroquinolones (e.g.,
      pneumococci and organisms causing atypical pneumonia), are considerably more
      sensitive to levofloxacin. The pharmacokinetics of levofloxacin, which is
      available for both oral and i.v. administration, are characterised by a very high
      bioavailability, low (30-40%) protein binding, high tissue concentrations and
      elimination via the kidneys with minimal liver metabolism. As a consequence of
      the low degree of metabolism, levofloxacin does not interact with other drugs to
      any major extent. The safety and efficacy of levofloxacin are well documented in
      lower respiratory tract infections, skin and soft tissue infections, and urinary
      tract infections. The safety profile seems advantageous and the risks of
      phototoxicity, CNS toxicity and cardiac reactions (prolongation of QT-time) are
      low. Serious liver toxicity, leading to the recent withdrawal of trovafloxacin,
      has not been a problem in levofloxacin studies. Levofloxacin is a valuable
      addition to the group of fluoroquinolone antibiotics.

PMID- 11249555
TI  - The pharmacology of donepezil: a new treatment of Alzheimer's disease.
AB  - Donepezil (donepezil hydrochloride, E-2020, Aricept, Eisai), launched in March
      1997, was the first drug to be marketed for the symptomatic treatment of
      Alzheimer's disease (AD) in the UK. It had been launched a year earlier in the US
      where clinicians had already had experience of tacrine (THA). Donepezil is a
      piperidine based, potent, specific, non-competitive and reversible inhibitor of
      acetylcholinesterase (AChE). It is structurally dissimilar from other established
      cholinesterase inhibitors, namely THA (an acridine compound) and the carbamates,
      physostigmine and rivastigmine and has a pharmacokinetic and tolerability profile
      distinct from these agents. Experimentally, donepezil inhibits AChE activity in
      human erythrocytes and increases extracellular acetylcholine levels in the
      cerebral cortex and the hippocampus of the rat. Pharmacologically, donepezil has
      a half-life of approximately 70 h lending itself to once daily administration.
      The most common adverse events reported in clinical trials have been
      gastrointestinal, typically nausea, vomiting, diarrhoea and constipation.
      Headache, dizziness and sleep disturbance have also been reported; there has been
      no evidence of hepatotoxicity. Clinically a number of placebo-controlled trials
      have shown that donepezil 5 or 10 mg daily was associated with significant
      improvements in cognitive function, as assessed by the Alzheimer's disease
      Assessment Scale-cognitive subscale (ADAS cog) after 12 or 24 weeks treatment.
      Significant improvements in global function and activities of daily living have
      also been demonstrated after 24 weeks treatment compared with placebo in patients
      with mild to moderate AD. Donepezil was the first rational treatment available in
      the UK for this disabling condition and as such received considerable attention.
      Much of the original attention was negative, ostensibly based on the scientific
      view that there was not enough published evidence to justify widespread use, but
      this was driven by concerns about the potentially high drug costs if all patients
      with AD were eligible to receive it. Considerable data have now been produced
      from Phase II, III and post-marketing surveillance. This drug evaluation will
      review the basic pharmacology of donepezil and place it in context with the trial
      data and the author's clinical experience with the drug.

PMID- 11249556
TI  - Sildenafil.
AB  - Sildenafil (Viagra, Pfizer, Inc.) is a new orally effective therapy for the
      treatment of men with erectile dysfunction (ED). It is a specific and selective
      inhibitor of phosphodiesterase Type 5 (PDE5), an enzyme which is an important
      modulator of smooth muscle relaxation in the corpus cavernosum. In the presence
      of a sexual stimulus, inhibition of PDE5 results in improved smooth muscle
      relaxation within the sinusoids of the corpus cavernosum and the penile arteries.
      This results in improved erections in men with ED. In clinical trials, sildenafil
      has been found to be effective in improving the erections of large numbers of men
      with ED secondary to a range of causes. The presence of PDE5 in other tissues
      such as vascular smooth muscle results in side effects such as headache,
      flushing, indigestion and nasal congestion. These side effects are dose-dependent
      and well-tolerated. The introduction of sildenafil in many countries around the
      world has revolutionised the assessment and treatment of men with ED.

PMID- 11249558
TI  - Evaluation of the drug treatment regimens for inflammatory bowel disease.

PMID- 11249557
TI  - Miglitol, a new alpha-glucosidase inhibitor.
AB  - Miglitol (Bay m 1099, Bayer) is a second generation alpha-glucosidase inhibitor.
      It is a derivative of 1-desoxynojirimycin, and binds reversibly to the
      brushborder alpha-glucosidase enzymes. In contrast to its parent drug (acarbose,
      Bay g 5421, Bayer), miglitol is almost completely absorbed in the small
      intestine. It has to be taken with each main meal, and through its effect on
      carbohydrate digestion it blunts the postprandial blood glucose increase.
      Miglitol has no or a very small effect on fasting blood glucose levels. The blood
      glucose lowering effects of miglitol in patients with Type 2 diabetes are lower
      than those of the frequently-used sulphonylurea compounds. Long-term studies show
      that a moderate average reduction of HbA1c of 0.3-0.7% point from baseline can be
      achieved. An advantage over sulphonylurea is the effect on serum insulin levels:
      miglitol therapy leads to slightly lower postprandial levels of serum insulin,
      whereas chronic sulphonylurea treatment usually increases serum insulin levels.
      This insulin-sparing effect may, in theory, lead to a lesser weight gain or even
      no weight gain and reduced risk of hypoglycaemia during chronic treatment. Long
      term experience in Type 1 diabetic patients is limited. Similarly, miglitol may
      lead to reduced postprandial glucose excursions, slightly reduced insulin
      requirements and perhaps, as a consequence, a lower risk of hypoglycaemia. More
      long-term data are needed to fully assess to the clinical use of miglitol in
      these patients.

PMID- 11249559
TI  - Tiludronate. A new treatment for an old ailment: Paget's disease of bone.
AB  - Tiludronate ([[(4-chlorophenyl)thio]-methylene]-bis-phosphonate, ClPsMBP, Skelid,
      Sanofi) is a powerful inhibitor of bone resorption which has been shown to be a
      highly effective and safe agent for the treatment of Paget's disease of bone.
      Preclinical studies in vitro and in vivo have demonstrated a dose-dependent
      inhibitory effect on bone resorption. Unlike other bisphosphonates, tiludronate
      does not seem to interfere with the differentiation of osteoclasts or with their
      access to bone mineral. Bone tolerance studies indicate that tiludronate has an
      excellent therapeutic window. Thus, at the doses which induce a substantial
      inhibition of bone resorption it neither causes an appreciable effect on
      mineralisation, nor impairs biomechanical bone resistance. New formulations of
      tiludronate (tablets) have a bioavailability of 6% (2-11%) when ingested under
      optimal conditions. The pharmacokinetic profile of tiludronate is linear.
      Approximately 50% of the absorbed dose is bound to bone and the rate of release
      from this site is limited by bone turnover. Several open uncontrolled, open
      randomised, and double-blind, placebo-controlled studies carried out in patients
      with active Paget's disease have demonstrated that tiludronate reduces bone pain
      and produces an intense and sustained biochemical response. 3-6 months after
      starting tiludronate therapy, serum alkaline phosphatase levels fall far more
      than 50% from baseline values, reaching normal values in a percentage of the
      cases ranging from 35-70%. At present, tiludronate, together with pamidronate and
      alendronate, appear to be the drugs of choice for first-line use in the
      management of relatively young patients at risk of having long-term
      complications, when long-lasting control of disease activity is required.

PMID- 11249560
TI  - Nitric oxide scavengers in the treatment of shock associated with systemic
      inflammatory response syndrome.
AB  - Shock associated with systemic inflammatory response syndrome (SIRS) is a form of
      distributive shock affecting over 200,000 patients per year in the US that
      results in 50% mortality. The role of NO in a variety of shock states has been
      extensively studied and has been shown to be the primary effector in endotoxin
      lipopolysaccharide (LPS)-induced hypotension attendant to shock associated with
      sepsis or presumed sepsis. NO has also been shown to be a myocardial depressant,
      an inhibitor of mitochondrial electron transport, an inducer of vascular leakage
      and an enhancer of LPS-induced cytokine release. Hence, it is involved in a wide
      variety of shock-related pathologies and is a key target for therapeutic
      intervention. Mechanism of action based therapies using NO scavengers represent a
      promising new approach. However, because NO is involved in such a wide variety of
      both physiological and pathophysiological processes, a therapy directed at NO
      must be selective in order to be both safe and effective. NO scavengers are
      comprised of two basic classes: organic molecules and metal complexes.
      Pyridoxalated haemoglobin polyoxyethylene conjugate (PHP) is a chemically
      modified haemoglobin. It is the furthest advanced NO scavenger in clinical trials
      and is about to enter pivotal Phase 3 trials in patients with shock associated
      with SIRS.

PMID- 11249561
TI  - Current pharmacotherapy for inflammatory bowel disease.
AB  - Ulcerative colitis (UC) and Crohn's disease (CD), collectively termed
      inflammatory bowel disease (IBD), are chronic spontaneously relapsing
      enteropathies of unknown aetiology. Pharmacotherapy for IBD has essentially been
      unchanged for over twenty years, with therapy based around 5-aminosalicylic acid
      (5-ASA) preparations, corticosteroids, antibiotics and immunosuppression. Much of
      the controversy surrounding optimal use of these drugs in IBD arises as a
      consequence of methodological deficiencies in many of the early trials combined
      with the difficulty in consistent patient selection due to the heterogeneous
      nature of both UC and CD. More recently, well-designed clinical trials have
      attempted to provide an 'evidence based' approach to managing IBD which, in time,
      will allow optimisation of current therapies and accurate evaluation of novel
      agents. Over the past two decades, improved research methodology has considerably
      increased our molecular understanding of the aetiopathogenesis of IBD which has
      ultimately lead to the development of specific mediator directed or 'designer'
      drug therapy for IBD. This review evaluates the literature on current IBD
      therapy, summarises the important recent studies which have made an impact on
      clinical practice, and examines the risks and benefits of the novel agents which
      are currently under investigation in clinical trials of IBD therapy.

PMID- 11249562
TI  - Current management of tuberculosis.
AB  - Current chemotherapeutic regimens against tuberculosis give excellent cure rates
      and low relapse rates if implemented and monitored correctly. This is fortunate
      since only two new drugs have been approved for use in this condition in the last
      30 years. However, shortcomings in management and in patient compliance have
      resulted in an increasing prevalence of drug-resistant organisms. The global
      decline in the disease has been reversed due to a combination of factors
      including the HIV epidemic, ageing populations, poverty, and translocation of
      refugee populations due to conflict.

PMID- 11249563
TI  - Evaluation of the drug treatment regimens for pulmonary tuberculosis and their
      cost-effectiveness.
AB  - According to the World Health Organization (WHO), in 1995 up to one-third of the
      total global population were estimated to be infected with the tubercle bacilli
      with nearly 90% of cases occurring in the developing countries. In addition, the
      1999 WHO report on tuberculosis (TB) estimated the total number of new sputum
      positive cases to have been just over 3.5 m globally in 1997. The incorrect usage
      of the available drugs has lead to drug-resistant forms of the bacteria which has
      further complicated the treatment needs and the costs imposed on healthcare
      services. Faced with this scenario it is important that a comprehensive policy is
      adopted to make best use of the existing drugs and to do so in a cost-effective
      way. This article considers the studies conducted on drug treatment regimens for
      pulmonary TB and their cost-effectiveness in the developing world.

PMID- 11249564
TI  - New formulations of drugs in epilepsy.
AB  - The advent of numerous new treatment options in epilepsy therapy over the last
      decade is enabling a more flexible and individualized approach to patients with
      seizures. For some patients, these products offer added efficacy, reduction of
      troublesome side effects associated with standard anticonvulsants, and control
      over acute seizure exacerbations. This review profiles new formulations of anti
      epileptic drugs. Tegretol-XR (TXR) and Carbatrol (CBTL), two extended-release
      preparations of carbamazepine (CBZ), which allow twice daily administration,
      minimising drug toxicity and improving efficacy. Topiramate sprinkles and
      lamotrigine chewable dispersible tablets allow easier administration in children.
      The rectal gel preparation of diazepam (Diastat) is useful for parents of
      patients with acute seizure exacerbations. Intravenous valproate (Depacon) and
      fosphenytoin (Cerebyx) provide parenteral treatment of acute seizures, without
      sedation or significant peripheral venous side effects. All of these new
      formulations expand treatment options for patients with epilepsy, who will
      benefit from them.

PMID- 11249565
TI  - An assessment of the present and future roles of non-ligand gated ion channel
      modulators as CNS therapeutics.
AB  - Few approved drugs have, as their primary known mechanism of action, modulation
      of non-ligand gated ion channels. However, these proteins are important
      regulators of neuronal function through their control of sodium, potassium,
      calcium and chloride flux, and are ideal candidates as drug discovery targets.
      Recent progress in the molecular biology and pharmacology of ion channels
      suggests that many will be associated with specific pharmacological profiles that
      will include both activators and inhibitors. Ion channels, through their
      regulation by G-proteins, are a major component of the final common pathway of
      many drugs acting at classical neuronal receptors. Thus, targeting of the ion
      channels themselves may confer different profiles of efficacy and specificity to
      drug action in the brain and spinal cord. Three areas for drug discovery are
      profiled that the authors consider prime targets for ion channel based therapies,
      anticonvulsant drugs, cognition enhancing drugs and drugs for improving neurone
      survival following ischaemia.

PMID- 11249566
TI  - Management of essential hypertension.
AB  - Hypertension, in spite of a very high prevalence, remains undertreated. This is
      not due to a lack of effective therapeutic modalities. Non-pharmacological
      treatments can be effective in many patients. If those treatments fail to reduce
      blood pressure sufficiently, the physician can choose between numerous classes of
      antihypertensive agents. However, interpatient variability in response to these
      agents is high, and use of multiple agents is frequently necessary. Thus, no
      single class has proven to be superior for the majority of patients. This article
      will review the different non-pharmacological and pharmacological methods
      available to treat hypertension, as well as the guidelines that are available to
      aid in proper selection of a treatment regimen.

PMID- 11249567
TI  - Pharmacotherapy of atrial fibrillation.
AB  - Atrial fibrillation (AF) remains a widespread health problem and the drugs
      available for its treatment suffer from several drawbacks, including potentially
      lethal proarrhythmia, serious non-cardiac toxicity and limited efficacy. The
      evidence for efficacy of currently available anti-arrhythmic agents for sinus
      rhythm restoration and maintenance is reviewed, with emphasis on randomised
      trials when available. The current approach to thromboembolism prophylaxis in AF
      is summarised.

PMID- 11249568
TI  - Clinical applications of recombinant human growth hormone in adults.
AB  - The main function of growth hormone (GH) is to promote linear growth during
      childhood; however, GH secretion persists throughout life after cessation of
      skeletal growth. This hormone has important physiological functions apart from
      growth stimulation. Many aspects of the physiological and pharmacological actions
      of GH have been recently clarified. Accordingly, in the last years, especially
      since the introduction of recombinant human GH (rhGH), GH therapeutical
      applications have increased. In the last years, the main clinical application of
      rhGH has been to stimulate growth of growth-retarded GH deficient (GHD) children.
      More recently, rhGH therapy has been approved for other conditions associated
      with short stature, including Turner syndrome and end stage renal disease. In
      adults, the only therapeutic indications approved are the adult GHD syndrome and
      the AIDS-associated wasting. This review outlines the present knowledge of the
      physiological effects, clinical applications, therapeutic perspectives, side
      effects, precautions and contraindications of rhGH therapy in adults.

PMID- 11249569
TI  - Macrolide antibiotics as biological response modifiers.
AB  - Erythromycin was first isolated in the 1950s from a Philippine soil sample, and
      the derivatives of erythromycin A, called the macrolide antibiotics, have been
      used as effective antibacterial agents ever since. It has long been suspected
      that the 14-membered macrolides have immunomodulatory activity as demonstrated by
      their early use as adjunctive therapy for asthma and their astounding
      effectiveness for the therapy of diffuse panbronchiolitis. It is now clear, that
      the macrolides and their cousins, the 15-membered azalides, and perhaps the
      ketolides, have a broad range of biological response modifying effects on
      inflammation, tumor cells, airway secretions and host defenses. This review
      highlights some exciting new data, as well as controversies related to
      understanding the mechanism of action for these diverse effects.

PMID- 11249570
TI  - Synercid Aventis.
AB  - Rhone-Poulenc Rorer (RPR) developed Synercid (RP-59500), an injectable
      synergistic combination of quinupristin and dalfopristin as a treatment for a
      variety of infections caused by Gram-positive anaerobic bacteria. The treatment
      was approved in the UK in July 1999, for use in patients with nosocomial
      pneumonia, skin and soft tissue infections and clinically significant infections
      due to Enterococcus faecium when there is no other active antibacterial agent
      [337556,335257]. It was launched in the UK and the US in September 1999 [342899].
      In December 1999, Synercid successfully completed the Mutual Recognition
      Procedure in the EU under Aventis Pharma for use in patients with these
      infections [351525]. In September 2000, Merrill Lynch predicted first-year sales
      in 1999 of Euro 15 million, rising to Euro 171 million in 2004 [384874]. In
      January 1999, BT Alex Brown predicted sales of US $88 million in 1999 rising to
      US $450 million in 2002 [318220]. In April 1999, ABN Amro predicted annual sales
      of DM 30 million in 1999, rising to DM 150 million in 2002 [328676].

PMID- 11249571
TI  - Linezolid Pharmacia Corp.
AB  - Linezolid is an oxazolidinone developed by Pharmacia (formerly Pharmacia &
      Upjohn) for the treatment of multi-resistant Gram-positive infections
      [187765,317456]. It binds to ribosomal 50S subunits, most likely within domain V
      within the 23S rRNA peptidyl transferase and a secondary interaction with the 30S
      subunit. This results in inhibition of the initiation of protein translation at
      an early point, which is probably N-formylmethionyl-tRNA [335843]. No direct
      action on DNA or RNA synthesis has been observed [220169]. Linezolid resistance
      due to a 23S rRNA mutation may emerge in Enterococci during therapy with this
      antimicrobial, and may be associated with clinical failure [368652]. Following
      FDA approval, linezolid was launched in May 2000 [368526,368652]. In April 2000,
      the FDA approved linezolid injection, tablets and oral suspension for the
      treatment of patients with infections caused by Gram-positive bacteria. It is
      indicated for adults in the treatment of nosocomial pneumonia, community-acquired
      pneumonia (CAP), complicated and uncomplicated skin and skin structure infections
      and vancomycin-resistant enterococcus (VRE) infections caused by methicillin
      resistant Staphylococcus aureus (MRSA), VRE faecium and penicillin-susceptible
      Streptococcus pneumoniae [363503]. The FDA, however, did not grant Pharmacia
      indications for linezolid in the treatment of CAP due to either penicillin
      resistant S aureus (PRSA) or MRSA. In May 2000, Merrill Lynch predicted sales for
      2000 to be US $50 million, rising to US $760 million in 2004 [366910]. In
      February 2000, P&U predicted that peak sales of the drug had the potential to
      reach in excess of US $750 million [358429]. In February 1999, Morgan Stanley
      Dean Witter predicted sales of US $40 million in 2000 rising to US $275 million
      in 2005 [319855]. In December 1998, Deutsche Bank predicted sales of US $100
      million in 2000 rising to US $300 million in 2002 [316769].

PMID- 11249572
TI  - TNF inhibitors in the treatment of arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic destructive arthritis leading to joint
      destruction as a consequence of chronic inflammatory processes. Established
      therapy with slow-acting disease-modifying anti-rheumatic drugs (DMARDs), as with
      low-dose methotrexate (MTX), leads to a significant improvement of disease
      symptoms, but are unable to stop joint destruction. Novel therapeutic agents like
      monoclonal antibodies (mAb), cytokine receptor-human immunoglobulin constructs or
      recombinant human proteins have been tested in RA and in other chronic
      arthritides like ankylosing spondylitis or psoriatic arthritis with convincing
      success. In particular, clinical trials testing anti-TNF alpha agents either
      alone or in combination with MTX have proven the feasibility and efficacy of
      these novel approaches.

PMID- 11249573
TI  - MFG-IRAP University of Pittsburgh.
AB  - The University of Pittsburgh is developing MFG-IRAP gene therapy for the
      potential treatment of arthritis. Phase II studies have commenced, including one
      trial in arthritis patients [225365]. A retrovirus (MFG-IRAP) is used in the ex
      vivo transfer of a cDNA encoding the human interleukin-1 receptor antagonist (IL
      1Ra). The therapy is being tested in post-menopausal women, and involves the
      removal of some of their synovium, which is then transfected with the IRAP gene
      and reimplanted into the joint [188197]. A phase I rheumatoid arthritis trial of
      a therapy using the IL-1 antagonist gene therapy in synergy with soluble TNF
      alpha receptors was reported in March 1999 and was considered to be effective in
      producing an anti-arthritic effect [318398].

PMID- 11249574
TI  - Vitaxin applied molecular evolution.
AB  - Vitaxin is a humanized version of LM-609 (an mAb licensed from the Scripps
      Research Institute and Dr David Cheresh in May 1994, which blocks the integrin
      receptor, alpha v beta 3) [172038]. It is in phase II trials for the potential
      treatment of leiomyosarcoma [316471] and is also being studied in phase I trials
      as an anti-inflammatory and potential rheumatoid arthritis therapy
      [364031,313665]. Vitaxin and non-peptides are under evaluation for use in the
      treatment of other diseases in which vitronectin is reputed to play a role, e.g.,
      arthritis, psoriasis and other inflammatory diseases. Patent positions are being
      established on these and other applications, as well as on the structure and use
      of the non-RGD proteins [182507].

PMID- 11249575
TI  - The potential of PDE4 inhibitors in asthma or COPD.
AB  - At least 11 families of distinct phosphodiesterase (PDE) isoenzymes are known to
      regulate the function of many cells secondary to altering the intracellular
      levels of second messengers including cyclic 3'5-monophosphate (cyclic AMP) and
      cyclic 3'5 guanosine monophosphate (cyclic GMP). While there is a wide
      distribution of these enzymes throughout the body, it is of interest that
      inflammatory cells thought to participate in the pathogenesis of inflammatory
      diseases including asthma and chronic obstructive pulmonary disease (COPD),
      preferentially express PDE4. This finding has stimulated the search for highly
      selective inhibitors of these enzymes. Unfortunately, PDE4 inhibitors tend to be
      associated with a number of unwanted side effects including headache and emesis.
      However, attempts have been made through rational drug design to synthesize
      compounds that demonstrate improved side effect profile. Such drugs offer an
      exciting opportunity to selectively downregulate inflammatory cell function as a
      novel therapeutic approach in the treatment of airway disease.

PMID- 11249576
TI  - Novel immunopharmacological strategies for allergic asthma.

PMID- 11249577
TI  - Norastemizole Sepracor.
AB  - Sepracor and Janssen are developing the histamine H1 antagonist, norastemizole
      (an active metabolite of Johnson & Johnson's Hismanal), for the potential, non
      sedating treatment of allergy. Sepracor expects to file an NDA with the FDA by
      the fourth quarter of 2000 [337315,358429]. As of September 1999, Sepracor was
      conducting two large-scale phase III seasonal allergic rhinitis studies [340260].
      Sepracor expects norastemizole to be the most potent non-sedating histamine, with
      equal or more rapid onset of action than other therapies [229516]. Norastemizole
      is 13- to 16-fold more potent as an H1 antagonist than astemizole and 20- to 40
      fold more potent in inhibiting histamine-induced bronchoconstriction. Following a
      single dose of norastemizole (25 mg p.o.), there is significant attenuation of
      histamine-induced wheal and flare responses within 30 min. The drug's major
      advantage is its lack of cardiotoxicity or interactions with other drugs that
      increase the risk of developing serious arrhythmias [301469]. In July 2000,
      Morgan Stanley Dean Witter predicted filing for FDA approval for allergic
      rhinitis during the first half of 2001, and a partnership announcement around the
      time of this NDA filing. The analysts also forecast European sales of $8.3
      million in 2002, rising to $16.7 m by 2005 [384868].

PMID- 11249578
TI  - ZD-0892 AstraZeneca.
AB  - ZD-0892, a neutrophil elastase inhibitor, is under development by AstraZeneca as
      a potential treatment for chronic obstructive pulmonary disease (COPD) and
      peripheral vascular disease (PVD). It is in phase I clinical trials for these two
      indications [315489]. The compound was originally under investigation for the
      potential treatment of asthma, but development was discontinued for this
      indication [266604]. The compound is the follow-up to ZD-8321 (qv) [336599].

PMID- 11249579
TI  - Recent developments in glycine antagonists.
AB  - This paper covers the relevant scientific and patent literature published in the
      last two years concerning different classes of glycine antagonists and their
      potential application to therapeutic targets. Many of the molecules described
      here are approaching the final stages of clinical studies.

PMID- 11249580
TI  - Robalzotan AstraZeneca.
AB  - AstraZeneca (formerly Astra) is developing robalzotan, a 5-HT1A antagonist, for
      the potential treatment of depression and anxiety. The compound has entered phase
      II trials, and NDA and MAA filings are expected after 2003 [352095,377656]. In
      August 2000, Lehman Brothers predicted that the compound had a 20% probability of
      reaching the market, with a predicted launch date of 2005 [384880].

PMID- 11249581
TI  - Vanoxerine National Institute on Drug Abuse.
AB  - Vanoxerine (GBR-12909) is a high-affinity dopamine reuptake inhibitor that was
      synthesized in the late 1970s and was initially tested in Europe as a potential
      antidepressant. In 1989, it was suggested that GBR-12909 might be useful in the
      treatment of cocaine addiction [346980]. The drug has completed phase I clinical
      trials conducted by the US National Institute on Drug Abuse for the potential
      treatment of cocaine abuse [346245,376621]. A multidose, safety and
      pharmacokinetics, open-label, fixed-order dose-escalating study has been
      completed. Four doses of vanoxerine in healthy normal volunteers were
      administered, to assess the safety and tolerability of the drug at 25, 50, 75 and
      100 mg. Further development is likely to continue, pending review of the data
      [376621]. Dopamine transporter occupancy has also been measured. After 2 weeks of
      dosing at either 50, 75 or 100 mg oral vanoxerine in 8 human subjects,
      preliminary results of subsequent PET scans show that occupancy increased with
      dose, reaching 25 to 35% at 100 mg [346245]. At these doses, the drug did not
      cause the behavioral symptoms such as those of cocaine, suggesting that the drug
      does not have abuse potential. If no safety issues arise, the compound will be
      evaluated in trials with cocaine-dependent subjects, along with its derivative,
      compound 5 [346980]. It is thought that prolonged treatment with vanoxerine could
      reverse the addiction process, following studies in rats showing that dopamine
      transporter levels returned to normal when animals were switched to vanoxerine
      therapy immediately after cocaine administration [346980]. Vanoxerine has an
      affinity constant (Ki), at the human dopamine transporter, of 9 nM [347021]. Gist
      Brocades originally initiated studies of vanoxerine, along with another
      piperazine, GBR-12935, for the treatment of cocaine dependence. The company was
      also investigating vanoxerine as a potential antipsychotic therapeutic agent;
      development for this indication has been discontinued [190331]. In 1995, the NIDA
      began to fund studies into the potential of vanoxerine to reduce cocaine self
      administration by rhesus monkeys. Early data showed that vanoxerine could
      decrease cocaine-maintained responding (CMR) in rhesus monkeys, without affecting
      similar levels of food-maintained responding (FMR). Furthermore, a decanoate
      ester of a hydroxylated analog of vanoxerine, DBL-583, could decrease CMR by 80%
      while leaving FMR unaffected; this effect lasted almost 30 days with a single
      injection [227488,346980]. Similar studies have shown that, by inhibiting the
      dopamine transporter, for which vanoxerine has a 500-fold increased affinity in
      comparison to cocaine, vanoxerine could selectively reduce(1 mg/kg i.v.) or
      eliminate (3 mg/kg i.v.) cocaine self-administration in primates. The drug was
      well tolerated with no changes in blood pressure or oxygen saturation. Oral
      administration of the drug in clinical trials was planned following this study
      [346990].

PMID- 11249582
TI  - SPIKET and COBRA compounds as novel tubulin modulators with potent anticancer
      activity.
AB  - Agents that either promote or inhibit tubulin polymerization exhibit anticancer
      activity by disrupting normal mitotic spindle assembly and cell division as well
      as inducing apoptosis. Recently identified novel agents that target tubulin
      include synthetic spiroketal pyrans (SPIKET), targeting the spongistatin binding
      site of beta-tubulin, and COBRA compounds, targeting a unique binding cavity on
      alpha-tubulin. At nanomolar concentrations, the SPIKET compound SPIKET-P caused
      tubulin depolymerization in cell-free turbidity assays and exhibited potent
      cytotoxic activity against cancer cells as evidenced by destruction of
      microtubule organization, and prevention of mitotic spindle formation in human
      breast cancer cells. Molecular modeling studies predicted a high-affinity
      interaction of the first COBRA compounds, COBRA-0 and COBRA-1, with a unique
      hydrophobic binding site on alpha-tubulin located between the GTP/GDP binding
      site and the M-loop. Further studies showed that COBRA-1 inhibited GTP-induced
      tubulin polymerization in cell-free tubulin turbidity assays. Treatment of human
      breast cancer and brain tumor (glioblastoma) cells with COBRA-1 caused
      destruction of microtubule organization and apoptosis. COBRA-1 activated the pro
      apoptotic c-Jun N-terminal kinase (JNK) signal transduction pathway. COBRA and
      SPIKET compounds represent two new classes of tubulin targeting agents that show
      promise as anticancer drugs.

PMID- 11249583
TI  - Tiazofurine ICN Pharmaceuticals.
AB  - Tiazofurine is a nucleoside analog with oncolytic activity being developed by
      Ribapharm (formerly ICN Pharmaceuticals) as a potential treatment for leukemia.
      It is metabolized to TAD (thiazole-4-carboxamide adenine dinucleotide), an
      inhibitor of IMP dehydrogenase. This inhibition results in the reduction of
      guanylate levels and the halting of neoplastic proliferation. The compound is in
      phase II/III trials [215553]. It is expected that Ribapharm will file an orphan
      drug application for tiazofurine, as a treatment for myelogenous leukemia,
      following the drug's completion of phase III trials by the end of 2002. The
      company has reported that phase III trials will begin by the end of 2000.
      Preliminary studies involving 21 patients have been carried out and the results
      reported by the company. During these studies, seven patients with chronic
      myelogenous leukemia had a complete hematologic response and two patients had a
      partial response. Of the patients with a complete response, six had marrow and
      peripheral responses. Ribapharm, through a Russian subsidiary of ICN, is also
      planning to conduct phase II studies of tiazofurine involving patients suffering
      from advanced ovarian cancer or multiple myeloma which is resistant to
      conventional therapy. The company has reported that the multiple myeloma limited
      phase II study is still undergoing planning, with an intended start date in late
      2000 [381453]. In March 2000, Chase Hambrecht & Quist predicted that first
      approval could be towards the end of 2001 [384894].

PMID- 11249584
TI  - ZD-0473 AstraZeneca.
AB  - ZD-0473 (formerly JM-473 and AMD-473) is a sterically hindered platinum (II)
      complex designed and synthesized by Johnson Matthey Technology and the Cancer
      Research Campaign (CRC) and under development as a potential treatment for
      cisplatin-resistant cancer. AstraZeneca is developing both an i.v. and an oral
      formulation of ZD-0473. In December 1999 the i.v. formulation entered phase II
      clinical trials for the potential treatment of solid tumors; the oral formulation
      is undergoing preclinical development [351298,349551]. AstraZeneca expects to
      file for registration of the drug in the fourth quarter of 2002 [377656]. Phase I
      clinical trials for the potential treatment of a range of solid tumors, including
      colorectal cancer were carried out jointly by AnorMED (a subsidiary of Johnson
      Matthey) and the CRC at the Royal Marsden Hospital, UK [301848,315489,337657].
      AstraZeneca has licensed ZD-0473 from AnorMED and is responsible for the
      worldwide development of the drug beyond phase I trials [337540]. Phase I trials
      to determine the maximum tolerated dose in patients, the nature of the dose
      limiting toxicity and the pharmacokinetics of the drug commenced in the US in
      November 1999 [347964]. In June 2000, Deutsche Bank predicted sales of US $15
      million in 2003 [374500]. In March 1999, Lehman Brothers predicted a 15%
      probability that the drug would reach worldwide markets, and be launched onto the
      market in 2003 [336599].

PMID- 11249585
TI  - Potential of 5-HT-moduline as a drug target for affective disorders.
AB  - The serotonergic system is one of the aminergic neurotransmitter systems
      participating in the maintenance of homeostasis of the organism in mammals;
      accordingly, it regulates the activity of various cerebral functions to organize
      adapted responses of the brain to environmental stimuli. The regulatory activity
      of the serotonergic system itself is modulated by an endogenous mechanism based
      on an allosteric interaction involving a newly discovered peptide, 5-HT-moduline,
      and the 5-HT1B receptor which, as an autoreceptor, controls the release of 5-HT
      from serotonergic neuron terminals. 5-HT-moduline specifically interacts with 5
      HT1B receptors at nanomolar concentrations resulting in the desensitization of
      the receptor. As 5-HT1B autoreceptors have an inhibitory effect on the release of
      5-HT, 5-HT-moduline ultimately increases its release. The peptide is
      characterized by several criteria which correspond to those of a
      neurotransmitter, strongly suggesting that 5-HT-moduline is a novel neuropeptide
      locally controlling serotonergic activity. 5-HT-moduline is released in various
      parts of the brain, particularly under conditions of stress; moreover, its
      deactivation by specific antibodies in mice induces changes in the behavior of
      the animal. These results strongly suggest that the peptide may play a role in
      the physiopathology of central nervous system disorders in mammals, particularly
      in conditions related to stress and anxiety. Furthermore, the fact that 5-HT
      moduline increases the release of 5-HT suggests that synthetic drugs which
      recognize the 5-HT-moduline binding site on 5-HT1B receptors and mimic the effect
      of the peptide, may have antidepressant properties by increasing the release of 5
      HT.

PMID- 11249586
TI  - BP-897 Bioprojet.
AB  - BP-897 is a dopamine D3 receptor agonist which is under development by Bioprojet
      for the potential treatment of drug craving and vulnerability to relapse that are
      elicited by drug-associated environmental stimuli; it is undergoing phase I
      trials [318397,334036,340721]. Preclinical investigations were carried out by
      Cambridge University and INSERM [295680]. BP-897 functions as a partial agonist
      in vitro and as either an agonist or an antagonist in vivo. It inhibits cocaine
      seeking behavior that depends upon the presentation of drug-associated cues,
      without having any intrinsic, primary rewarding effects [334036]. In preclinical
      studies, BP-897 administration before testing reduced cocaine-seeking behavior in
      rats in a dose-dependent manner [304557,307758,334036]. In D3 receptor knockout
      mice, BP-897 has no effect [345710]. It does not reduce self-administration of
      cocaine in monkeys [318397].

PMID- 11249587
TI  - Duloxetine Eli Lilly & Co.
AB  - Lilly is developing duloxetine, a 5-HT and norepinephrine uptake inhibitor as a
      potential treatment for depression and urinary incontinence. In Japan, it is
      being jointly developed with Shionogi [187401]. Phase III trials for depression
      and phase II trials for urinary incontinence are underway in Japan
      [296442,328887]. Lilly expects to file for depression in 2002 and phase III
      trials for urinary incontinence are planned to start enrollment by the end of
      2000 [358429,370526,373870]. Duloxetine has a half-life of 10 to 15 h in humans,
      and parameters reach a steady-state after 3 days of daily administration. In a 6
      week, open-label study duloxetine was safe and well tolerated in 79 clinically
      depressed patients. Clinical response occurred in 78% of patients, and remission
      occurred in 60%. Insomnia and nausea occurred with an incidence of 20% [300881].
      Duloxetine may offer advantages over existing antidepressants, such as Lilly's
      fluoxetine, because of faster recovery and fewer side effects [190226]. In June
      2000, Morgan Stanley Dean Witter predicted duloxetine would reach the market in
      2002 with annual sales in this year of US $50 million, rising to $200 million in
      2005 [373870]. In February 1999, Deutsche Bank predicted Lilly's sales at US $200
      million in 2002 rising to $400 million in 2003 [316821]. In May 2000, Deutsche
      Bank had made further predictions, stating that filing for duloxetine is expected
      in the fourth quarter of 2001, and peak sales are expected to exceed US $500
      million. Also in February 1999, Lehman Brothers predicted the first major launch
      date (US and ex-US) to be 2002, with the year of peak sales to be 2008 [319225].
      In August 1999, this prediction changed, and the expected launch date became
      2001, with an 80% probability of reaching the market and sales peaking at US $150
      million in 2012 [349228].

PMID- 11249588
TI  - Oncological applications of gene therapy.
AB  - Despite the rapid technological advances that continue to sustain the field of
      cancer gene therapy, few individual patients have benefited from the revolution
      so far. The plethora of clinical trials described confirms that each malignancy
      will have its own ideal strategy based on the associated molecular defects, and
      there has been rapid progress from this viewpoint. At the same time, there has
      been a renewed appreciation for the limitations to gene therapy, which include
      low efficiency of gene transfer, poor specificity of response and methods to
      accurately evaluate responses, and lack of truly tumor-specific targets at which
      to aim. As with all new therapies, we are climbing a steep learning curve in
      terms encountering treatment-related toxicities, as well as profound ethical and
      regulatory issues.

PMID- 11249589
TI  - Tezacitabine Hoechst Marion Roussel.
AB  - Tezacitabine (MDL-101731, KW-2331, FMdC), an antimetabolite deoxycytidine analog,
      is an irreversible ribonucleotide reductase inhibitor and DNA chain terminator
      discovered by Hoechst Marion Roussel, now Aventis Pharma, and under development
      by Matrix and Kyowa as a potential treatment for solid tumors [117987,153697]. It
      is in phase II trials for colorectal and hematological cancer
      [333949,343071,353481] and was evaluated in a phase II trial for non-small cell
      lung cancer, for which enrollment was reported to have stopped [342009]; however,
      tezacitabine continues to be explored for this indication [378351]. In February
      1999, the first phase II trial patient was treated with tezacitabine. A total of
      30 patients with non-small cell lung cancer were expected to be enrolled by
      Matrix [316463]; however, in October 1999, Matrix closed enrollment in this trial
      (after 28 patients were enrolled); preliminary analysis of the evaluable patients
      did not show meaningful clinical activity with tezacitabine as a stand-alone
      therapy in this indication at the dose and regimen tested [342009]. In May 1999,
      Matrix announced it would enroll up to 30 colorectal cancer patients for
      treatment in a phase II study [326017]. Despite closing enrollment for the NSCLC
      trial, as of October 1999, the phase II trial of tezacitabine in colorectal
      cancer was continuing to accrue patients [342009]. In March 2000, a clinical
      trial was initiated at the University of Pennsylvania to study tezacitabine
      administered intravenously in combination with cisplatin; a phase I trial
      studying the drug in combination with 5-FU at the Dana Farber Cancer Institute
      also commenced at that time [360590]. In May 1999, the results of four phase I
      trials were presented at the 35th Annual Meeting of the American Society of
      Clinical Oncology (ASCO). The studies enrolled 70 patients, 97% of whom had had
      previous chemotherapy and 46% of whom had failed three or more prior regimens.
      Groups of patients were given i.v. infusions of tezacitabine in schedules ranging
      from once every 3 weeks to twice a week for 3 weeks at doses ranging from 16 to
      630 mg/m2. The dose-escalation studies showed the compound to be well tolerated
      and indications of efficacy were observed in patients with various advanced solid
      tumors [325070,327102]. In September 1998, Matrix Pharmaceutical acquired
      worldwide rights to tezacitabine except in Japan [299373]. Kyowa Hakko Kogyo has
      a license from HMR to develop tezacitabine in Japan [195494]; in 1995, the
      company began phase I clinical trials in Japan for tezacitabine administered
      orally [195494]. In 1996, this product was designated one of HMR's nine top
      priority products, serving an unmet medical need and addressing a potential
      market in excess of US $500 million per year [221118].

PMID- 11249590
TI  - ZD-9331 AstraZeneca.
AB  - AstraZeneca (formerly Zeneca) is developing ZD-9331, a non-polyglutamatable
      thymidylate synthase inhibitor, as a potential treatment for solid tumors and
      other neoplasia, including colorectal tumors [216476,179954,179955]. ZD-9331 is
      being developed as both an oral and an i.v. formulation, both of which are in
      phase II trials as of December 1999 [349551,352095]. As of June 1998, ZD-9331 was
      in phase II trials for advanced colorectal and other solid tumors [315489], with
      drug filings not expected until 2002 [349551]. A clinical study presented at the
      36th Annual Meeting of the American Society of Clinical Oncology (ASCO)
      demonstrated that treatment with ZD-9331 resulted in a period of intracellular 2'
      deoxyuridine (dUrd) elevation, a surrogate marker of thymidylate synthase
      inhibition, with observed myelosuppression being no greater than that seen with
      raltitrexed and less than with bolus 5-FU [369475]. Results from a 56-patient
      phase I study were presented at the 1999 ASCO meeting. Dose escalation followed a
      two-stage procedure. As in previous studies myelosuppression was the dose
      limiting toxicity, occurring at 4.8 and 7.5 mg/m2/day, with one patient at each
      of these two doses experiencing a DLT. The MTD was not achieved until 12 to 16
      mg/m2/day, based on which a fixed dose of 25 mg/day was being evaluated [326935].
      A number of other studies are ongoing, comparing once to twice daily dosages as
      well as the pharmacokinetics of the compound. Encouraging phase I data have been
      seen in melanoma, ovarian, colon and breast cancer; myelosuppression is the dose
      limiting toxicity in the majority of these studies [326938,326943,326945,327399].
      A phase I dose-escalation trial was conducted to evaluate the feasibility of a
      once 3-weekly 30-min i.v. infusion of ZD-9331, with doses ranging from 4.8 to 370
      mg/m2. The regimen was overall well tolerated up to 370 mg/m2, with grade IV
      myelosuppression and grade IV diarrhea being observed in a small number of
      patients [288959,377842]. In June 2000, Deutsche Bank predicted sales of $12
      million in 2002 [374500]. In January 1999, ABN Amro predicted sales of US $8
      million in 2002 rising to $66 million in 2005 [316250, 328676]. In March 1999,
      Lehman Brothers predicted a 30% probability that the drug would reach the
      worldwide markets, and be launched in 2002 [336599].

PMID- 11249591
TI  - Effectiveness of fluoroquinolones against gram-positive bacteria.
AB  - Fluoroquinolones are broad-spectrum and therapeutically effective antibacterial
      agents that have retained high activity against methicillin-susceptible
      Staphylococcus aureus (MSSA) and streptococci. Primary targets of these agents in
      Gram-positive bacteria are DNA topoisomerase and DNA gyrase. High-level
      resistance is associated with at least two mutations in either target, or
      combinations of at least two mutations in multiple targets, particularly
      affecting the ParC subunit of topoisomerase IV and the GyrA subunit of DNA
      gyrase. This resistance may be enhanced when combined with mutations that
      increase fluoroquinolone efflux. Data from fluoroquinolone-resistant clinical
      isolates suggest that as yet unidentified mutations may also be involved in
      clinical resistance.

PMID- 11249592
TI  - Olamufloxacin. Hokuriku Seiyaku.
AB  - Hokuriku is developing olamufloxacin, a quinolone antibiotic that inhibits DNA
      gyrase, for the potential treatment of various types of bacterial infection. It
      has reached late phase II clinical trials. An intravenous formulation is also
      under investigation [277817].

PMID- 11249593
TI  - Gatifloxacin Kyorin Pharmaceutical Co.
AB  - Gatifloxacin is a novel fluoroquinolone with a 3-methylpiperazine group at
      position 7 of the quinolone ring and a methoxy group at position 8
      [287520,379131]; the 8-methoxy substituent seems to decrease the rate of
      development of resistance in Gram-positive bacteria [378631]. Gatifloxacin
      appears safe and effective [286426,342518,378432] and has been approved in the US
      and several other countries for the treatment of community-acquired pneumonia
      (CAP), acute bacterial exacerbation of chronic bronchitis, acute sinusitis,
      uncomplicated skin and skin structure infections, uncomplicated urinary tract
      infections, complicated urinary tract infections and pyelonephritis,
      uncomplicated urethral, endocervical, pharyngeal and rectal gonorrhea
      [352761,359434].

PMID- 11249594
TI  - Moxifloxacin Bayer.
AB  - Bayer has launched the fluorinated oxoquinolone, moxifloxacin, as a treatment for
      bacterial infection. It was launched in Germany for the treatment of respiratory
      tract infections in September 1999, and regulatory approval in the other EU
      member states was expected to be completed early in 2000, with marketing
      throughout the EU by the end of 2000 [336340,340358]. Moxifloxacin received FDA
      approval in December 1999 and it was launched in the same month
      [350407,350415,365913]. By July 2000, the drug had been launched in Japan
      [375976]. In February 1999, Lehman Brothers predicted 95% probabilities that
      moxifloxacin would reach the US and ex-US markets, and launch onto these market
      in 1999. Peak annual sales of US $500 million in 2005 (US) and US $800 million in
      2007 (ex-US) are predicted [319225].

PMID- 11249595
TI  - Pazufloxacin Toyama Chemical Co.
AB  - Toyama Chemical Co Ltd is developing pazufloxacin (T-3761), an orally active
      synthetic quinolone antibiotic, which is awaiting registration following
      successful clinical trials that demonstrated its pharmacological similarities to
      tosufloxacin (Toyama Chemical Co) with respect to clinical efficacy, adverse
      effects and overall safety [272136]. As of June 2000, the company had filed an
      NDA for marketing approval in Japan [373027]. The company is also developing an
      injectable formulation, pazufloxacin mesylate (T-3762), which has entered phase
      III trials in Japan [228819]. There is a licensing agreement with Welfide Corp
      (formerly Yoshitomi/The Green Cross Corp) in Japan [228819].

PMID- 11249596
TI  - Oral toleragens in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a common inflammatory and destructive arthropathy.
      Its precise pathogenesis remains unknown but there is evidence to suggest it is
      an autoimmune disease. Recently, a number of candidate autoantigens have been
      identified in RA. Modulating the immune response to the autoantigens by oral
      tolerance may lead to safer and more effective treatment. Oral tolerance is a
      state of systemic immune suppression to an antigen induced by oral feeding of the
      same antigen. In animal models, oral feeding with pathogenic antigens prevents
      and reduces the severity of autoimmune diseases. Even in diseases where the
      pathogenic autoantigens are unknown, bystander suppression can be induced using
      antigens present in the anatomical vicinity. Hence, oral tolerance has been
      advocated as a treatment strategy for autoimmune diseases including RA. Clinical
      trials of chicken and bovine type II collagen, a major constituent of articular
      cartilage, produced conflicting results in RA. This review examines the
      scientific basis of oral tolerance, discusses the apparent discrepancy in
      clinical trial results and looks at the future prospect.

PMID- 11249597
TI  - Anti-inflammatory and immunomodulatory therapies in spondyloarthropathies.
AB  - Although the spondyloarthropathies constitute amongst the commonest chronic
      inflammatory joint disorders, there have been few therapeutic advances since the
      introduction of nonsteroidal anti-inflammatory agents. A number of disease
      modifying therapies originally developed for rheumatoid arthritis have also been
      examined in this class of arthritides, although placebo-controlled studies are
      lacking. Despite the low interest from industry, there is the promise that
      emerging therapies, particularly bisphosphonates and tumor necrosis factor alpha
      antagonists may be efficacious. Significant impediments to the development of
      additional therapeutic agents include a limited understanding of
      immunopathological events operative in early disease, disease heterogeneity, the
      inability to detect structural damage with adequate sensitivity, and the high
      cost of treatment. However, the recent development of internationally
      standardized and validated clinical outcome assessment tools as well as
      sophisticated magnetic resonance imaging are rekindling interest in these
      disorders.

PMID- 11249598
TI  - AnergiX.RA Corixa.
AB  - Corixa (formerly Anergen), in collaboration with Organon, is developing
      AnergiX.RA, a complex of solubilized HLA DRB1-0401(a) together with a specific
      peptide from the human cartilage glycoprotein HCgp39, for the potential treatment
      of rheumatoid arthritis (RA) [307156]. Phase I/II trials were completed in April
      2000 and the final results from the randomized, blinded, placebo-controlled dose
      escalation study are expected later this year [363409]. The product utilizes
      Anergen's AnergiX technology, and combines an MHC-derived protein with an Organon
      autoantigen peptide, derived from myelin basic protein and involved in the
      development of RA [212659,363409]. Engagement of T-cell receptors with AnergiX.RA
      induces apoptosis in autoreactive T-cells [227421]. Researchers at Organon
      identified the central component in AnergiX.RA; results from preclinical studies
      identifying this target protein were published in June 1997 in Arthritis &
      Rheumatism. Researchers demonstrated that HC (human cartilage) gp39 is recognized
      by T-cells from RA patients and has the potential to block arthritis in the mouse
      model [248543,354821].

PMID- 11249599
TI  - Developments in the treatment of chronic obstructive pulmonary disease: the
      clinical picture.

PMID- 11249600
TI  - Tryptase inhibitors in the treatment of pulmonary diseases.

PMID- 11249601
TI  - BP-294 Ste Civile Bioprojet.
AB  - BP-294 (a prodrug of R-alpha-methylhistamine) is a histamine H3 agonist under
      development by Bioprojet and in phase II clinical trials as an antiasthmatic
      [219798]. In a study, R-alpha-methylhistamine was shown to inhibit the release of
      acetylcholine, in the presence of atropine (1 microM) and 0.5 Hz of electrical
      stimulation of the rat bilateral vagus nerve, in a dose-dependent manner. This
      inhibition was abolished by thioperamide [321838].

PMID- 11249602
TI  - Carebastine Almirall Prodesfarma.
AB  - Carebastine, a histamine H1 antagonist, is under development by Almirall
      Prodesfarma for the potential treatment of allergic rhinitis, asthma and
      conjunctivitis. A nasal formulation was submitted for registration in Spain in
      June 1999 [343595]. It is also in phase III trials for conjunctivitis and phase I
      trials for asthma [343144,343243]. In a multicentered, multinational, double
      blind, placebo-controlled study in patients with symptomatic SAR, patients were
      assigned a nasal spray formulation of carebastine (2.5 mg/ml) or placebo.
      Severity scores decreased significantly with carebastine compared to placebo.
      This findings suggest that carebastine nasal spray has the potential to be of
      value in the treatment of SAR [282185]. In a multicenter, multinational, double
      blind, randomized, placebo-controlled study, patients with seasonal allergic
      conjunctivitis (SAC) were assigned an eye drop formulation of carebastine (25
      mg/ml) or placebo. Carebastine was significantly better than placebo at relieving
      the effects of SAC, as early as 15 min after administration and the effect lasted
      for 14 days. Carebastine was well-tolerated and there were no difference in
      adverse events between the two groups [282897].

PMID- 11249603
TI  - Methylprednisolone suleptanate Pharmacia Corp.
AB  - Methylprednisolone suleptanate (Promedrol) is a prodrug of methylprednisolone
      being developed by Pharmacia Corp (formerly Pharmacia & Upjohn) for the treatment
      of asthma. It has been approved for this indication in Switzerland and is
      awaiting registration in several other countries [211246]. Preliminary
      preclinical data indicated the potential use of methylprednisolone suleptanate
      for the i.v. treatment of immunological disease. Its anti
      inflammatory/bronchodilatory effect was demonstrated in mice and rats and in a
      guinea pig model [271975]. Animal models have also demonstrated the use of
      methylprednisolone suleptanate for the treatment of nephritis and hypotension.
      Efficacy and safety of pulse therapy Promedrol was demonstrated in a phase II
      trial using lupus nephritis patients. The recommended dose for pulse therapy is
      400 mg equivalent/day i.v. [271975]. Other studies in lupus patients have shown
      that doses of up to 1000 mg/day are well tolerated [307789] and pulse therapy
      with either 400 or 800 mg/day are efficacious in delaying the onset of CNS
      symptoms in SLE patients with organic brain disease [307512]. Preclinical studies
      are also taking place for the potential treatment of spinal cord injury [344254].
      In April 2000, Morgan Stanley Dean Witter estimated sales would be US $281
      million in 2003, rising to $277 million in 2004 [375906].

PMID- 11249604
TI  - Drug discovery in a new century: mechanistic opportunities and therapeutic
      challenges.

PMID- 11249605
TI  - New norditerpenoid alkaloids from Aconitum hemsley anum var. pengzhouense.
AB  - Two new norditerpenoid alkaloids, 13-deoxyludaconitine (1) and 8
      deacetylsungpaconitine (3), were isolated from the roots of Aconitum hemsleyanum
      Pritz var. pengzhouense and their structures were elucidated by spectral data.

PMID- 11249606
TI  - New Hurghamids from a Red Sea sponge of the genus Hippospongia.
AB  - Three new N-acyl-2-methylene-beta-alanine methyl esters, Hurghamides E-G (5-7),
      were isolated from a Red Sea sponge Hippospongia sp. Their structures were
      elucidated by extensive spectroscopic studies.

PMID- 11249607
TI  - An isopimarane diterpene from Euphorbia ebracteolata Hayata.
AB  - From the ethanolic extract of the roots of Euphorbia ebracteolata Hayata four
      compounds were isolated. They are 24-methylenecycloartanone, tirucallol,
      procesterol and a new isopimarane diterpene, namely yuexiandajisu C. The
      structure of yuexiandajisu C was elucidated by spectral analysis. The bioassay in
      vitro showed yuexiandajisu C exhibited immunomodulatory activity.

PMID- 11249608
TI  - Analysis of phytoecdysteroids in cultured plants of Ajuga nipponensis makino.
AB  - Cultured plants of Ajuga nipponensis contained cyasterone (1), ajugasterone C
      (2), cyasterone-22-acetate (3) and 22-dehydrocyasterone (4) based on HPLC and NMR
      data, whereas 20-hydroxyecdysone was not detectable. The presence of compounds 2
      4 is reported for the first time in this species. Compound 1 is the main
      phytoecdysteroid component found in both preblossom and blossom plants, but the
      latter contained higher amount than the former. Compared with other parts of the
      plant, the highest percentage of 1 and 3 occurred in leaves, amounting to 60.1%
      and 88.0% respectively, whereas the flowers contained mainly 2, which represented
      72.8% of the total amount in whole plant. The contents of phytoecdysteroids in
      stems were very low.

PMID- 11249609
TI  - Structural revision of four spiramine diterpenoid alkaloids from the roots of
      Spiraea japonica.
AB  - On the basis of detailed 1H-NMR 13C-NMR spectral analysis, especially by 2D NMR
      experiments (1H-1H COSY, HMQC, HMBC, and NOESY) as well as by chemical
      transformations. four isoatisine type diterpenoid alkaloids, spiramines P and Q,
      and U and T, have been reassigned as the 6beta hydroxyl and 6beta acetoxyl
      substituents, respectively, rather than the previously assigned 15alpha
      counterparts in our further studies on chemical constituents of the roots of
      Spiraea japonica var. acuta.

PMID- 11249610
TI  - Two new caffeoyl conjugation from Erigeron breviscapus.
AB  - Two new constituents with a novel basic skeleton were isolated from Erigeron
      breviscapus. On the basis of chemical and spectroscopic evidences, the structures
      of the new compounds were elucidated as 1R,3R-dihydroxy-4S,5R-dicaffeoyloxy
      cyclohexane carboxylic acid methyl ester (V), 1,4-dihydroxy-3R,5R-dicaffeoyloxy
      cyclohexane carboxylic acid methyl ester (VI).

PMID- 11249611
TI  - Justicia lignans VI--prostalidin D, a new arylnaphthalide lignan from Justicia
      diffusa var. prostrata C.B. Clarke.
AB  - A new arylnaphthalide lignan, prostalidin D (6) was isolated as a minor
      metabolite from Justicia diffusa var. prostrata. 6 contains a rare catechol unit
      and its structure was confirmed by total synthesis. In addition, seven known
      lignans, namely, justicidin E (7), helioxanthin (8), justicidin A (9),
      medioresinol dimethyl ether (10), medioresinol (11), lariciresinol (12) and 8
      methoxyisolariciresinol (13) have also been isolated from the same source and
      identified by direct comparison with authentic samples.

PMID- 11249612
TI  - Dihydroayapin, a new coumarin compound from Dendrobium densiflorum.
AB  - A new coumarin named dihydroayapin (1) together with seven known compounds were
      isolated from the stems of Dendrobium densiflorum. On the basis of
      physicochemical and spectral evidences, the structure of 1 was established as 6,7
      methylenedioxy-3,4-dihydrobenzopyran-2-one.

PMID- 11249613
TI  - N-acetylation and N-formylation of m-aminobenzoic acid by cell suspension
      cultures of Solanum laciniatum.
AB  - Two new biotransformation products, N-acetyl-m-aminobenzoic acid and N-formyl-m
      aminobenzoic acid were isolated from cell suspension cultures of Solanum
      laciniatum following administration of m-aminobenzoic acid, and their structures
      were elucidated using one- and two-dimensional 1H- and 13C-NMR data.

PMID- 11249614
TI  - Three new taxane diterpenoids from the seeds of the Chinese yew, Taxus chinensis
      var mairei.
AB  - Three new taxoids were isolated from the seeds of the Chinese yew, Taxus chinesis
      var mairei, their structures were established as 9alpha, 13alpha-diacetoxy-5alpha
      cinnamoyloxy-11(15-->1)-abeo-taxa-4(20),11-diene-10beta, 15-diol,
      2alpha,9alpha,10beta-triacetoxy-taxa-4(20),11-diene-5alpha,13alpha-diol and
      2alpha,7beta,10beta-triacetoxy-5alpha-cinnamyloxy-9alpha-hydroxy-taxa-4(20),11
      diene-13-one on the basis of 1D, 2D NMR, and MS spectral analyses.

PMID- 11249615
TI  - Antihyperglycemic effects of gymnemic acid IV, a compound derived from Gymnema
      sylvestre leaves in streptozotocin-diabetic mice.
AB  - We investigated the antihyperglycemic action of a crude saponin fraction and five
      triterpene glycosides (gymnemic acids I-IV and gymnemasaponin V) derived from the
      methanol extract of leaves of Gymnema sylvestre R. BR. (Asclepiadaceae) in
      streptozotocin (STZ)-diabetic mice. The saponin fraction (60mg/kg) reduced blood
      glucose levels 2 4h after the intraperitoneal administration. Gymnemic acid IV,
      not the other 4 glycosides at doses of 3.4-13.4mg/kg reduced the blood glucose
      levels by 13.5-60.0% 6h after the administration comparable to the potency of
      glibenclamide, and did not change the blood glucose levels of normal mice.
      Gymnemic acid IV at 13.4 mg/kg increased plasma insulin levels in STZ-diabetic
      mice. Gymnemic acid IV (1 mg/mL) did not inhibit alpha-glycosidase activity in
      the brush border membrane vesicles of normal rat small intestines. These results
      indicate that insulin-releasing action of gymnemic acid IV may contribute to the
      antihyperglycemic effect by the leaves of G. sylvestre. Gymnemic acid IV may be
      an anti-obese and antihyperglycemic pro-drug.

PMID- 11249616
TI  - Web alert. Antisense--from design to clinic.

PMID- 11249617
TI  - Antisense oligonucleotide technology: from EST to therapeutics.
AB  - The ability to selectively inhibit gene expression with antisense
      oligonucleotides could have profound effects upon future biological research,
      including functional genomics, and the ways in which many diseases are treated.
      This review describes cell culture-based research pertaining to the selection of
      optimal antisense effector sequences, their desired and non-antisense mechanisms
      of action and their delivery into the appropriate intracellular compartments.
      Preclinical and clinical use of antisense technology is examined and probable
      future directions that this may take are discussed. Overall, the current state of
      antisense oligonucleotide research described here promises a highly productive
      future for this technology.

PMID- 11249618
TI  - The disposition (ADME) of antisense oligonucleotides.
AB  - Antisense oligonucleotides hold great promise as novel therapeutic agents
      designed to specifically and selectively inhibit the production of various
      disease-related gene products. For efficacy to occur, the therapeutic entity must
      reach the site of action in amounts sufficient to produce the desired therapeutic
      effect. Pharmacokinetics is defined as the study of the time course of the
      absorption, distribution, metabolism and elimination (ADME) of drugs. An
      understanding of the pharmacokinetics of antisense oligonucleotides and, in
      particular, the mechanisms by which oligonucleotides accumulate in tissues and in
      cells are critical to understanding the limitations of this technology and
      ultimately the development of effective antisense therapeutics. This review
      summarizes the known observations on the pharmacokinetics of antisense
      oligonucleotides with particular attention to contributions (non-clinical and
      clinical) published during the interval 1997 to 2000. Principles underlying the
      ADME of oligonucleotides are presented at the beginning of each section.

PMID- 11249619
TI  - Toxicological evaluation of oligonucleotide therapeutics.
AB  - In this brief review, guidance is provided for the safety evaluation of
      phosphorothioate oligonucleotides. This novel class of compounds has proved to be
      challenging for the preclinical development scientist, as systemic exposure can
      evoke sometimes dramatic responses, in terms of general functional parameters,
      laboratory data (hematology, clinical chemistry) and histopathology of target
      organs. The polyanionic profile of these compounds is discussed vis-a-vis
      historical data for related structures. Dose-related responses in various
      laboratory test species are described. The liver, kidneys and immune system are
      major target organs, and an experimental perspective is provided for
      understanding each of these in determining a safe starting dose for clinical
      trials with novel compounds.

PMID- 11249620
TI  - Hybridization of antisense reagents to RNA.
AB  - Despite the simplicity of the concept, almost every step in an antisense
      experiment poses difficulties. Finding a site that is accessible to
      intermolecular hybridization with complementary nucleic acids is a major problem
      and determines the success or failure of an antisense experiment. A major
      determinant of accessibility appears to be the intramolecular folding in mRNAs
      that renders much of the molecule inaccessible. However, owing to our poor
      understanding of RNA folding and the mechanisms of heteroduplex formation,
      theoretical methods have limited use in finding accessible sites. Such methods
      are unable to address two major considerations when designing an antisense
      reagent, i.e., which is the most accessible sequence in the target and what
      length of the reagent works best in terms of activity and specificity. Empirical
      approaches appear more successful. Of notable interest, and reviewed here, are
      'global' methods based on DNA arrays and on mapping of transcripts with RNase H.

PMID- 11249621
TI  - Hammerhead ribozymes: biochemical and chemical considerations.
AB  - Ribozymes can be used to cleave specific mRNAs so as to prevent their
      translation. This presents an alternative to the use of antisense
      oligonucleotides for drug target validation or therapeutic purposes. The present
      review covers only one class of ribozymes, the hammerheads, which are small
      enough for chemical synthesis. Following an account of their structure and
      ability to catalyze the cleavage of target RNA is a discussion of some problems
      associated with their use as exogenous therapeutics. Chemical modifications that
      are used to address these issues are described.

PMID- 11249622
TI  - Antisense peptide nucleic acids.
AB  - Within the past couple of years peptide nucleic acid (PNA) antisense and antigene
      technology has entered the realm of biological and preclinical studies. This is
      primarily due to the development of a number of novel methods for more efficient
      delivery of PNA oligomers to eukaryotic cells. These methods have allowed ex vivo
      studies on cells in culture to be performed, and parallel in vivo studies are
      also slowly emerging. Although many issues still need to be resolved and several
      of the most recent results cannot be rationalized in a straight forward manner by
      existing knowledge, the immediate future should supply a more solid foundation
      for assessing the prospects of PNA antisense and antigene technology both in the
      context of functional genomics and medicine.

PMID- 11249623
TI  - Triplex-forming molecules for modulation of DNA information processing.
AB  - The design of specific DNA ligands is an important challenge in biological and
      biomedical sciences. Targeting the source of genetic information may allow highly
      efficient gene-directed modulation of cell function. Triplex-forming molecules
      specifically recognize oligopyrimidine/oligopurine sequences by hydrogen bonding
      interactions. In cell cultures they have been used successfully to downregulate
      or upregulate transcription in a gene-specific manner or to induce site-directed
      mutagenesis and recombination. For biotechnological applications, triplex-forming
      molecules are powerful tools for gene-specific chemistry.

PMID- 11249624
TI  - Aspects of the transport and delivery of antisense oligonucleotides.
AB  - This article will examine recent developments concerning the cellular uptake and
      subcellular trafficking of antisense oligonucleotides. It will also examine the
      merits of various delivery strategies for oligonucleotides. The use of conjugates
      of oligonucleotides with 'cell penetrating peptides' as a promising delivery
      technology will be emphasized.

PMID- 11249625
TI  - Development of antisense oligodeoxynucleotides for transplantation.
AB  - Over last ten years antisense technology has been improved to provide powerful
      tools to selectively inhibit production of different mRNAs. This technology has
      been applied in transplantation to prolong the survival of organ allografts and
      to prevent development of ischemic/reperfusion injury in grafts. The present
      review describes technological progress in chemical modifications from antisense
      phosphodiester oligonucleotides to phosphorothioate oligonucleotides and the most
      advanced chimeric oligonucleotides with methoxyethyl groups attached at both ends
      or at one end of the oligonucleotide. Results indicate that phosphorothioate
      oligonucleotides, designed to block intercellular adhesion molecule-1 (ICAM-1),
      extended the survival of heart and kidney allografts when administered to donors
      or recipients. Combination of ICAM-1 antisense phosphorothioate oligonucleotide
      and cyclosporine (CsA) produced a potent synergistic interaction on allograft
      survival in comparison with each drug alone. The same ICAM-1 phosphorothioate
      oligonucleotide used for perfusion of kidney grafts prevented development of
      ischemic/reperfusion injury. We also compared the effect of c-raf mRNA inhibition
      on heart allograft survival by phosphorothioate oligonucleotide or
      phosphorothioate/methoxyethyl oligonucleotide used alone or in combination with
      CsA or sirolimus (SRL). The results documented that addition of methoxyethyl
      modifications at both ends or at one end of oligonucleotides significantly
      improved the in vivo antisense activity. Combined therapy with c-raf antisense
      phosphorothioate/methoxyethyl oligonucleotide and SRL synergistically extended
      the survival of heart allografts. Thus, antisense technology may provide not only
      tools to examine the effects of selective inhibition of different molecules
      involved in allograft rejection but also act as potential therapeutic agents.

PMID- 11249626
TI  - Aptamers: selected oligonucleotides for therapy.
AB  - In vitro selection constitutes a unique way to explore vast libraries (up to
      10(14) to 10(15) different molecules) of randomly synthesized nucleic acids.
      Selected RNA or DNA sequences (aptamers) may help to understand the molecular
      interactions and processes of interest for human diseases. Aptamers can be
      chemically-modified for improved efficiency and use in complex biological media.
      Moreover, aptamers selected in vitro may retain their activity in vivo and thus
      offer novel perspectives for gene therapy and the design of new drugs.

PMID- 11249628
TI  - Technology evaluation: HIV ribozyme gene therapy, Gene Shears Pty Ltd.
AB  - Ribozymes (catalytic RNAs) can be made to specifically cleave target RNAs that
      are involved in disease conditions and therefore have potential as therapeutic
      agents. Gene Shears Pty Ltd is developing hammerhead ribozyme technology for
      therapy against HIV infection, targeting either the tat gene or the RNA packaging
      sequence (Psi) of HIV. These ribozymes have been expressed from constructs that
      were introduced into hematopoietic cells in culture, thereby protecting the cells
      against viral infection. Two phase I clinical trials are underway to test the
      safety and feasibility of the approach with the anti-tat ribozyme in human
      subjects.

PMID- 11249627
TI  - Patent review: therapeutic applications for antisense oligonucleotides 1999-2000.
AB  - Over 200 patents disclosing antisense sequences have been published in the last
      year. 30 Of these, in which a therapeutic application is claimed, have been
      reviewed in this article. We have classified these under the headings of
      antibacterial, antiviral, inflammation, cardiovascular, apoptosis and anticancer.
      Although not exhaustive or covering all diseases, major areas of antisense
      research have been addressed.

PMID- 11249629
TI  - Technology evaluation: transgenic antithrombin III (rhAT-III), Genzyme
      Transgenics.
AB  - AT-III LLC, a joint venture between Genzyme Transgenics (GTC) and Genzyme
      General, is developing transgenic recombinant human antithrombin III (rhAT-III)
      as a potential treatment for sepsis and other disorders involving thrombosis. It
      is in phase III clinical trials in the US and Europe as an anticoagulant in
      patients undergoing elective cardiac surgery such as cardiopulmonary bypass.

PMID- 11249630
TI  - Technology evaluation: FluMist, University of Michigan.
AB  - FluMist is an intranasal influenza vaccine, which has been developed by Aviron.
      The genetically engineered, live, attenuated, cold-adapted virus vaccine produces
      influenza infection without the symptoms. The product has been field for approval
      in the US, where Merrill Lynch expects it to be marketed by mid-2000 [336561].

PMID- 11249631
TI  - Web alert. Non-viral methods for gene transfer.

PMID- 11249632
TI  - Characterization of plasmids and formulations for non-viral gene therapy.
AB  - Analytical methods are described that provide a platform for systematically
      evaluating the effect of formulation variables in the development of DNA-lipid
      non-viral gene therapy complexes. The methods encompass those used to
      characterize the components, i.e., plasmid DNA and liposomes, as well as those
      applied to the complexes themselves. The focus is on physicochemical methods so
      that their parameters can be assessed in relationship to the functionality of the
      DNA-lipid complexes in vivo.

PMID- 11249633
TI  - Obstacles and advances in non-viral gene delivery.
AB  - This review focuses on recent progress and novel strategies to improve the
      efficiency of in vivo non-viral gene delivery. Examples of the most promising
      attempts to overcome specific barriers are presented in fuller detail. Current
      research into several of the most difficult steps in the gene delivery pathway is
      discussed including particle stabilization, targeting, cytoplasmic entry and
      access to the nucleus. The impact of recent reports on our current understanding
      of the true limitations to in vivo delivery is also discussed. The importance of
      preclinical animal models for the development of clinical applications of gene
      therapy is noted.

PMID- 11249634
TI  - Self-assembling complexes for in vivo gene delivery.
AB  - Non-viral DNA-containing particles represent a potentially attractive alternative
      to viruses for in vivo gene therapy applications. However, the inability to form
      small particles that remain stable and non-aggregating in vivo has limited their
      usefulness to date. The relatively simple self-assembling complexes that function
      so efficiently for in vitro gene delivery fail to provide similar gene delivery
      capabilities in vivo. Now for the first time, significant advances are being made
      into defining many of the in vivo barriers preventing stable particle formation.
      This improved understanding has been manifested into a rational design approach
      to DNA particle formation. This review highlights many of the recent studies in
      which rational design was employed in an effort to form polymer/DNA particles
      (polyplexes) that resist in vivo aggregation and inactivation.

PMID- 11249635
TI  - Advances in plasmid gene delivery and expression in skeletal muscle.
AB  - One of the most striking recent advances for plasmid delivery in vivo has been
      that of electropermeabilization, commonly referred to as electroporation. This
      physical process exposes a muscle tissue to a brief, high intensity electric
      field that induces temporary and reversible breakdown of the plasma membrane.
      During the period of membrane destabilization, a variety of molecules, including
      plasmids, gain intracellular access. Electroporation has been shown to improve
      the efficiency of plasmid gene delivery to skeletal muscle of small animals by as
      much as two-orders of magnitude to levels comparable to that of adenoviral gene
      delivery. This technology will allow the muscle to be used as a bioreactor for
      the secretion of therapeutic proteins into the circulation. This method of gene
      delivery, which is simple, efficient and reproducible, has become valuable for
      basic research, with great potential for gene therapy and DNA vaccination.
      Moreover, significant progress has been made using a variety of molecular designs
      to achieve regulation of gene expression by low molecular weight drugs. The
      enhanced efficiency of plasmid delivery by electroporation and the resultant
      durability of transgene expression, combined with the effectiveness of drug
      dependent transgene regulation systems, provide a powerful set of tools that will
      be broadly applicable to the development of plasmid-based gene therapies for the
      treatment of human disease.

PMID- 11249636
TI  - Targeted synthetic gene delivery vectors.
AB  - Synthetic gene delivery vehicles have made significant progress in the past
      decade in demonstrating strong potential for targeted delivery to specific cells,
      low toxicity and immunogenicity and large carrying capacity. However, significant
      advances must still be made to increase the efficiency of both polymer and lipid
      vehicles. Furthermore, techniques to generate more effective targeting moieties
      for a variety of cell types, as well as means to consistently assemble vectors
      containing these targeting ligands, are areas for further improvement. This
      review focuses on significant recent advances in generating a number of novel
      targeted vectors, and discusses progress in the development of new genetic and
      chemical systems to enhance the targeting, assembly and biocompatibility of
      synthetic vectors.

PMID- 11249637
TI  - Peptide-mediated cellular delivery.
AB  - Peptide-mediated molecular therapeutic delivery systems have recently emerged as
      an alternative means to effectively substitute or augment present gene therapy
      technologies, e.g., TAT, VP22, engineered peptides. These systems show great
      promise for the elimination of the main bottleneck to safe, efficient, targeted
      gene therapy delivery and are able to efficiently introduce DNA, antisense
      peptide nucleic acids, oligonucleotides, small molecules and proteins into cells
      both in vitro and in vivo. They are versatile and easily designed to incorporate
      a number of specific attributes required for efficient cargo delivery. A
      fundamentally new property of these moieties will allow the therapeutic
      intervention in the biochemistry of the target cell without the need to alter its
      genome.

PMID- 11249638
TI  - Non-viral gene delivery for p53.
AB  - Abnormality in the tumor suppressor gene p53 is one of the most common
      occurrences associated with human neoplasia. Consequently, restoration of wild
      type p53 function is seen as a particularly promising approach for cancer gene
      therapy. In recent years, considerable research effort has centered upon
      developing and improving non-viral delivery systems as alternatives to viral
      vectors for gene delivery. These methods include the use of lipoplexes and
      polyplexes, and even delivery of naked DNA. Optimally effective cancer gene
      therapy requires treatment of metastatic as well as local disease, and to achieve
      this end, systemic delivery systems for therapeutic genes will be required. This
      review will discuss some of the recent advances in ways to improve targeting,
      transfection efficiency and stability for systemic, non-viral p53 gene therapy.

PMID- 11249639
TI  - RNA transfected dendritic cells as cancer vaccines.
AB  - Immunization with dendritic cells loaded with tumor antigens could represent a
      powerful method of inducing antitumor immunity. Studies from several laboratories
      have shown that immunization with dendritic cells pulsed with specific antigens
      prime cytotoxic T-cells and engender tumor immunity. This review will focus on
      the use of dendritic cells transfected with RNA as cancer vaccines, with emphasis
      on the potential advantages of using RNA. The majority of cancer patients who
      lack an identified tumor antigen and/or cannot provide sufficient tumor tissue
      for antigen preparation will be excluded from treatment with cancer vaccines
      based on using either specific tumor antigens or mixtures of tumor-derived
      antigens in the form of peptides or proteins isolated from tumor cells.
      Vaccination with the mRNA content of tumor cells would extend the scope of
      vaccination to this group of patients as well because RNA can be amplified from
      very few cancer cells.

PMID- 11249640
TI  - Folate-targeted non-viral DNA vectors for cancer gene therapy.
AB  - The vitamin folic acid exhibits high affinity for the endocytosed, membrane-bound
      folate receptor. Conjugation of folic acid via its gamma-carboxyl group to
      various macromolecules results in binding to, and endocytosis into, cells
      expressing the folate receptor. The folate receptor is overexpressed on a wide
      range of cancers, therefore folic acid has been investigated as a targeting
      ligand for the specific delivery of therapeutic compounds to cancer cells. This
      review will introduce folate-targeting of macromolecules to cancer cells in vitro
      and in vivo, and discuss the accumulation of such compounds in non-target tissues
      in vivo. Folate-targeting of non-viral DNA vectors in vitro and in vivo will be
      discussed in detail, with particular emphasis on the recent advances in this
      field.

PMID- 11249641
TI  - DNA vaccines--challenges in delivery.
AB  - DNA vaccines are typically comprised of plasmid DNA molecules that encode an
      antigen(s) derived from a pathogen or tumor cell. Following introduction into a
      vaccine, cells take up the DNA, where expression and immune presentation of the
      encoded antigen(s) takes place. DNA can be introduced by viral or bacterial
      vectors or through uptake of 'naked' or complexed DNA. Vaccination with DNA is a
      recent technology possessing distinct advantages over traditional vaccines
      (killed or attenuated pathogens) and the more recently developed subunit
      vaccines. Unlike most subunit vaccines, DNA vaccines induce both the humoral and
      cellular arms of the immune response. The stimulation of both arms of the immune
      system is important not only for the prevention of many diseases including AIDS,
      but also allows the use of a vaccine for therapeutic purposes. While the
      traditional attenuated pathogen vaccines are also able to elicit both cellular
      and humoral immune responses, there is a risk of reversion from the attenuated
      state to the virulent state. This risk does not exist with DNA vaccines. DNA
      vaccines can be manufactured and formulated by generic processes. DNA vaccine
      technology, however, is still in its infancy and much research needs to be done
      to improve the efficiency with which these vaccines work in humans. While
      continued efforts toward improving both DNA expression and DNA delivery are
      equally important for increasing the utility of DNA vaccines, this review will
      focus both on non-viral delivery of plasmid DNA and delivery methods for the
      encoded antigen.

PMID- 11249643
TI  - Technology evaluation: electroporation therapy, Genetronics Inc.
AB  - Genetronics Inc has developed a MedPulser and a needle array applicator that
      delivers electric pulses to tumors and induces a transient permeabilization. Used
      in conjunction with intratumoral injections of anticancer drugs, this form of
      therapy, termed electroporation therapy, allows for intracellular accumulation of
      cytotoxic drugs without the toxic side effects associated with systemic
      administration. Accrual of preclinical data of electroporation therapy with
      bleomycin has led to clinical studies in patients with cutaneous and subcutaneous
      tumors. In 1999, objective responses were reported in a phase II study involving
      30 patients with head and neck cancer with minimal side effects [328332]. Other
      indications for this form of treatment include liver and pancreatic cancers,
      Kaposi's sarcoma and melanoma [273388,290144]. Genetronics Inc and Ethicon Endo
      Surgery (Johnson & Johnson Development Corp) are reviewing all clinical data from
      phase II studies prior to the initiation of a pivotal clinical trial in head and
      neck cancer.

PMID- 11249642
TI  - Technology evaluation: transgenic alpha-1-antitrypsin (AAT), PPL therapeutics.
AB  - PPL Therapeutics is developing transgenic alpha-1-antitrypsin for the treatment
      of cystic fibrosis lung disease and other conditions in which connective tissue
      is broken down irreversibly. AAT is a plasma protein that inhibits elastase, a
      key player in the inflammatory response that, unchecked, will lead to excessive
      tissue destruction. PPL has taken transgenic alpha-1-antitrypsin through phase II
      clinical trials in the cystic fibrosis lung, delivering it in aerosol form to
      assess its safety and efficacy [315887]. Although early results are not
      statistically relevant with respect to clinical benefit, they do show some
      promise, especially given the low numbers of patients studied and the complex
      phenotypes and severities associated with cystic fibrosis.

PMID- 11249644
TI  - Technology evaluation: thrombopoietin, Genentech/Pharmacia & Upjohn.
AB  - Thrombopoietin is a protein factor that promotes growth and platelet production
      and can be used to avert thrombocytopenia, which can cause uncontrolled bleeding
      in cancer patients undergoing chemotherapy. Genentech, having cloned the gene
      encoding thrombopoietin, are developing a recombinant protein technology in
      collaboration with Pharmacia & Upjohn for the potential treatment of
      thrombocytopenia in chemotherapy patients [274038]. The technology entered phase
      II/III clinical trials in 1998 and these were ongoing as of February 2000
      [355591].

PMID- 11249646
TI  - Technology evaluation: SELEX, Gilead Sciences Inc.
AB  - Systematic evolution of ligands by exponential enrichment (SELEX) technology has
      been under development for a decade, and is a general method for identification
      of oligonucleotide ligands as potential drugs. A pool of randomized RNA or single
      stranded DNA sequences were selected against certain targets. The sequences of
      tighter binding with the targets were isolated and amplified. The selection was
      repeated using the enriched pool derived from the first round selection. Several
      rounds of this process lead to winning sequences that are called 'aptamers' or
      'ligands'. This technology has been applied to a wide range of targets including
      various enzymes of HIV, growth factors and inflammation-inducing enzymes. The
      first aptamer that has proceeded to phase I clinical studies is NX-1838, an
      injectable angiogenesis inhibitor that can be potentially used to treat macular
      degeneration-induced blindness.

PMID- 11249645
TI  - Technology evaluation: MFG-IRAP, University of Pittsburgh.
AB  - The University of Pittsburgh is developing MFG-IRAP, a retroviral vector carrying
      the human interleukin-1 receptor antagonist protein (IRAP) cDNA for potential
      treatment of arthritis. MFG-IRAP gene therapy was effective in local gene
      delivery to synovial lining of joints and systemically to hematopoietic stem
      cells, in preclinical studies. Intra-articular expression of IRAP, although
      transient (4 to 6 weeks), was efficacious in several animal models of arthritis.
      On the other hand, systemic transgene expression was prolonged (15 months), but
      was relatively less efficacious. Clinical data on the safety of MFG-IRAP therapy
      per se are limited, however, recombinant IRAP studies in humans have not resulted
      in any serious adverse effects. Phase II studies, including a trial in arthritis
      patients should provide the much anticipated MFG-IRAP efficacy data.

PMID- 11249647
TI  - Technology evaluation: TG-1031, Transgene SA.
AB  - Tumor-associated antigens have considerable promise not only as diagnostic or
      prognostic markers but also as targets for active or passive immunotherapy. The
      epithelial mucin MUC1 is a transmembrane molecule which is expressed by most
      glandular epithelial cells. Transgene has developed VV-MUC1-IL-2 (TG-1031), an
      antigen-specific therapy, involving the tumor antigen MUC1 and the cytokine IL-2
      combined with a vaccinia virus vector. Vaccinia virus vectors have been shown to
      stimulate a strong immune response to encoded antigens in vivo. This therapy has
      potential for the treatment of breast cancer, prostate cancer and other
      adenocarcinomas and is currently under investigation in phase I and II trials.

PMID- 11249648
TI  - Web alert. Molecular vaccines for disease prevention and therapy.

PMID- 11249649
TI  - Clinical applications of dendritic cell vaccines.
AB  - Dendritic cells play a central role in the presentation of antigen to naive T
      cells and the induction of primary immune responses. Preclinical studies have
      established that dendritic cells loaded with antigens ex vivo induce potent
      antitumor and antiviral immune responses in vitro and in vivo. This has lead to a
      proliferation of clinical trials testing their effectiveness in humans,
      particularly with advanced malignancies. The few reported studies suggest that
      clinically relevant immune responses may be induced against some types of
      malignancies. Many questions regarding the best type of dendritic cell, degree of
      maturity, choice of antigen, route and schedule of administration, targeting to
      lymphoid tissue and use of additional adjuvants will need to be answered in
      preclinical and clinical studies as the field of dendritic cell-based
      immunotherapy progresses.

PMID- 11249650
TI  - Structural implications for the design of molecular vaccines.
AB  - The major histocompatibility complex molecules bind and present short antigenic
      peptide fragments on the surface of antigen presenting cells to T-cell receptors.
      Recognition of peptide-MHC by cytotoxic T-cells initiates a cascade of signals to
      T-cells, which in turn destroy the antigen presenting cell. In the design of
      molecular vaccines for the treatment of diseases, an understanding of the 3
      dimensional structure of MHC class I and is interaction with both peptide and T
      cell receptor is an important prerequisite. In this review, we will discuss such
      crystal structures, as well as structures of glycopeptides and alternative T-cell
      antigens presented by MHC molecules.

PMID- 11249651
TI  - Delivery systems for molecular vaccination.
AB  - Vaccination is one of the medical success stories of the 20th century, however,
      there are many diseases for which no prophylactic regimes are available. A major
      hindrance that has prevented the development of effective mass immunization
      programs is the inability to induce an appropriate, protective, immune response.
      For example, for vaccines against intracellular pathogens there is a requirement
      for cell-mediated immunity as characterized by cytolytic T-lymphocyte activity.
      However, such a response can be extremely difficult to elicit, especially those
      employing recombinant, soluble protein subunits. This deficiency is due to the
      inability of these antigens to access the machinery of the appropriate antigen
      processing pathway. Following an improved understanding of the mechanisms
      underlying such processing, as well as the realization that delivery systems can
      affect, quantitatively and qualitatively, the resulting immune response, the last
      decade has witnessed an intense research effort in this field. In this article we
      will review the major developments in the area of antigen delivery as related to
      vaccination.

PMID- 11249652
TI  - Notch signaling as a target in multimodality cancer therapy.
AB  - Notch signaling is an extremely conserved and widely used mechanism controlling
      cell fate determination. Recent evidence shows that Notch receptors regulate cell
      differentiation, proliferation and apoptosis in many cells, including neoplastic
      cells. In the context of cancer experimental immunotherapy and multimodality
      therapy, the Notch signaling network is acquiring increasing importance for its
      possible roles in both neoplastic cells and the immune system. In this review, we
      discuss: (i) the roles of Notch signaling in cancer cells and the immune system;
      and (ii) strategies through which Notch-targeting biologicals may be used to
      increase the effectiveness of multimodality cancer treatment, including cancer
      vaccines.

PMID- 11249653
TI  - Immune monitoring of cancer patients undergoing experimental immunotherapy.
AB  - Advancements in the understanding of cellular immunity within the last decade,
      along with the characterization of tumor antigens, have led to immunotherapeutic
      approaches for cancer therapy. This mode of treatment is expected to provide more
      tumor-specific activity, thereby being less toxic to normal cells than standard
      modalities. Clinical trials are underway throughout the world to determine
      whether immunotherapy is a practical and viable alternative to conventional
      cancer therapies. Unlike radiotherapy and chemotherapy, wherein tumor regression
      is the standard for determining efficacy of the regimens, immunotherapy has to be
      evaluated by the examination of several immunological parameters within patients.
      The purpose of this article is to review the methods currently utilized to
      evaluate the induction, maintenance, and duration of antitumor immune reactivity
      in cancer patients undergoing immunotherapy.

PMID- 11249654
TI  - Peptide mimotopes as candidate vaccines.
AB  - The development of combinatorial peptide libraries, where random peptide
      sequences are displayed either on the surface of a phage or on a solid support,
      provides researchers with a powerful tool for analysis and study of the
      specificity of immune responses. The strength of this technology lies in the
      large amount of molecular diversity displayed that can be easily obtained and
      rapidly tested. As a result of screening peptide libraries, novel peptide
      sequences can be identified, which mimic native protective epitopes (mimotopes),
      and have the potential for use as vaccine candidates.

PMID- 11249655
TI  - Development of oral vaccines for human use.
AB  - In developed and developing countries, oral vaccine formulations that elicit
      protection at mucosal surfaces are attractive vaccine candidates. Research has
      shown that vaccine delivery using either viral or non-viral vector delivery of
      heterologous proteins via the oral route is highly effective. Improvements in non
      viral vector uptake, specific targeting, antigen presentation and antigen release
      times will be required to overcome differences in the immune response following
      delivery. In contrast, the use of plant and animal viruses as vectors provides an
      effective method for targeted gene delivery. Recently, recombinant plant viruses
      grown in plants or transgenic plants have been proposed as edible vaccines for
      human use. Food plants offer many advantages as affordable, oral vaccines,
      especially for use in developing countries. Further research is necessary to
      develop strategies to improve immunological memory following oral vaccination and
      to avoid immunological tolerance in the host.

PMID- 11249656
TI  - Recent developments in mucosal delivery of pDNA vaccines.
AB  - The development of DNA vaccination to mucosal surfaces has continued apace over
      the last 2 years, with the investigation of several novel delivery vehicles.
      There have been advances in the understanding of the basic immunological
      mechanisms behind the induction of immune responses by plasmid DNA. The
      mechanistic insights are paving the way for the design of a second generation of
      mucosally delivered DNA vaccines. This article reviews the recent progress in the
      field of microparticle, cationic lipid and bacterial delivery systems. All these
      mechanisms afford some protection from environmental degradation and facilitate
      DNA uptake. These methods have been compared with respect to transfection
      efficiency, ability to elicit a full range of immune responses and their relative
      safety for in vivo applications.

PMID- 11249657
TI  - Live bacterial delivery systems for development of mucosal vaccines.
AB  - By expression of foreign antigens in attenuated strains derived from bacterial
      pathogens and in non-pathogenic commensal bacteria, recombinant vaccines are
      being developed that aim to stimulate mucosal immunity. Recent advances in the
      pathogenesis and molecular biology of these bacteria have allowed rational
      development of new and improved bacterial carriers and more effective gene
      expression systems. These advances have improved the performance and versatility
      of these delivery systems to induce mucosal immunity to recombinant antigens in
      animal models. Application of these (improved) technologies for development of
      human vaccines is still limited and awaits further exploration.

PMID- 11249658
TI  - Molecular therapeutics at the entrance into the 21st century.

PMID- 11249659
TI  - Web alert. Viral methods of gene transfer.

PMID- 11249660
TI  - Molecular therapy for glioblastoma.
AB  - Glioblastoma (GB), the relatively frequent and most malignant form of primary
      brain tumor, is fatal within 1 to 2 years of onset of symptoms, despite
      conventional therapy. Molecular therapy promises to be an effective and possibly
      curative treatment. Several molecular strategies have been tested, either in
      animal models or clinical trials. These include: prodrug activating systems,
      introduction of tumor suppressor or cell-cycle-related genes, inhibition of
      growth factors and/or their receptors, inhibition of neovascularization,
      immunomodulatory maneuvers, oncolytic viruses and inhibition of matrix
      metalloproteinases. Of special interest for the development of optimal molecular
      therapy of GB, is the choice of the most efficient and least toxic gene vectors
      (adenovirus, retrovirus, herpes simplex virus), the route of administration of
      the therapeutic agent (intratumoral with or without debulking and intracarotid),
      avoidance of collateral damage to the perineoplastic neuropil and adequate
      preclinical studies. The ultimate molecular therapy will probably involve the
      application of multiple simultaneous (combinatorial) therapeutic modalities. The
      safety and efficiency of these in humans can only be judged by properly
      controlled therapeutic trials.

PMID- 11249661
TI  - Animal xenograft models for evaluation of gene transfer into human hematopoietic
      stem cells.
AB  - Animal xenograft models of gene therapy have become increasingly popular to study
      the effects of various transduction strategies on human hematopoietic stem cells
      (HSC). Xenograft models provide an in vivo setting in which to monitor the
      duration and effects of vector expression in the progeny of the transduced stem
      and progenitor cells. Also, the ability of HSC to home to the bone marrow and
      differentiate into multilineage progeny following ex vivo manipulation can only
      be tested in a transplantation system. The current review will discuss the murine
      xenograft models that have been used recently to determine optimized methods for
      gene transfer into normal human hematopoietic stem cells.

PMID- 11249662
TI  - Viral vectors for gene transfer into antigen presenting cells.
AB  - Crucial insights for vaccine development have come from examining how the immune
      system responds to antimicrobial vaccines, as well as to viral vectors employed
      for gene therapy. The effectiveness of a vaccine depends upon both the method of
      antigen delivery and the presentation of antigen to lymphocytes. Much focus has
      turned to delivering antigens to dendritic cells, to promote clinically
      beneficial T- and B-cell responses. Recombinant viral vectors represent a
      powerful vehicle to deliver genes encoding microbial- or tumor-derived antigens
      to generate clinically beneficial immunity. Dendritic cell-based and viral vector
      based vaccines are currently being evaluated in clinical trials as a means of
      inducing antitumor immunity.

PMID- 11249663
TI  - Adenoviral vectors for liver-directed gene therapy.
AB  - Adenoviral vectors currently represent one of the most efficient means of in vivo
      hepatocyte gene delivery. Consequently, liver-directed gene transfer has been
      increasingly explored as a promising approach for the treatment of a diverse
      range of genetic and acquired diseases. Numerous demonstrations of efficacious
      adenoviral vector-mediated delivery of a wide array of transgenes in several
      animal species and humans have been reported. In general, transgene expression
      was efficient, but transient, in many cases lasting < 1 month. Currently, efforts
      in the field are focused on the development of highly attenuated adenoviral
      vectors designed to prolong transgene expression by reducing vector
      immunogenicity and hepatoxicity. Vector optimization strategies include the
      development of vectors devoid of all viral coding regions, the generation of
      chimeric vectors engineered to capitalize on favorable aspects of the component
      viral systems, the development of tissue-specific regulated gene expression, and
      the development of strategies to circumvent the host immune system. The use of
      adenoviral vectors for gene therapy of hereditary, malignant and infectious
      diseases of the liver, and the vector optimization strategies outlined above are
      discussed in this work.

PMID- 11249664
TI  - FGF2-targeted adenoviral vectors for systemic and local disease.
AB  - Adenoviral vectors have proven useful for transducing a variety of cell types.
      However, both adenoviral resistant cell types and vector-related toxicities (due
      to non-specific tropism), limit their widespread clinical utility. These
      limitations can be greatly reduced by targeting adenoviral vectors to alternative
      cell surface receptors. One ligand family, highly effective at targeting
      adenoviral vectors, is the family of fibroblast growth factors (FGFs). The FGFs
      allow a high degree of targeting specificity due to their cognate high affinity
      FGF receptors, which are expressed on cells undergoing repair and regeneration.
      Recent publications, reviewed herein, demonstrate that FGF-targeted adenoviruses
      result in enhanced potency and reduced toxicity, and thus substantially increase
      the therapeutic index in vivo. As a result, vector delivery through FGF receptors
      provides the targeting specificity required for successful local and systemic
      clinical applications of gene therapy.

PMID- 11249665
TI  - RNA-polymerase III-driven expression cassettes in human gene therapy.
AB  - tRNAs, U6 small nuclear RNA and adenovirus virus associated RNAs are transcribed
      by RNA polymerase III. These RNAs are expressed in high levels and possess
      increased stability due to their small, compact size. Promoters expressing these
      RNAs have therefore been used to express a variety of interfering RNAs, including
      ribozymes, antisense RNAs and sense or decoy RNAs. Intracellular expression and
      activity of RNA polymerase III-driven interfering RNAs have been demonstrated in
      several studies. This review will summarize the design and application of RNA
      polymerase III-driven expression cassettes in human gene therapy using retroviral
      vectors as the primary method of gene delivery.

PMID- 11249667
TI  - Retroviral vector-mediated gene expression in hematopoietic cells.
AB  - Gene transfer vectors based on simple retroviruses and more complex lentiviruses
      are currently the most reliable tools for stable establishment of transgenes in
      hematopoietic cells. While important hurdles in basic gene transfer technologies
      have been overcome in recent years, there is still some uncertainty in the choice
      of the cis-regulatory elements of the vector. These elements dictate the overall
      level, clonal variability, response to differentiation and persistence of
      transgene expression in vivo and thus have a significant influence on the outcome
      of therapeutic applications of somatic gene transfer. The rationale underlying
      the further improvement of such cis-elements is reviewed here.

PMID- 11249666
TI  - Facilitation of retrovirus-mediated gene transfer into hematopoietic stem and
      progenitor cells and peripheral blood T-lymphocytes utilizing recombinant
      fibronectin fragments.
AB  - A transduction strategy has been developed, using fibronectin (FN)-assisted
      retroviral-mediated gene transfer, based on the observation that hematopoietic
      stem and progenitor cells bind to specific adhesion domains of fibronectin, via
      the integrins, very late antigen-4 (VLA-4)alpha 4 beta 1 and very late antigen-5
      (VLA-5)alpha 5 beta 1. Retrovirus-mediated transduction on a recombinant FN
      fragment, FN CH-296, containing binding sites for VLA-4 and VLA-5, separated by
      type III repeats 12 to 14, makes it possible to efficiently target hematopoietic
      stem and progenitor cells and T-lymphocytes due to colocalization of target cells
      and retrovirus particles. These gene therapy strategies are applicable to the
      potential treatment of a variety of acquired and inherited immune disorders.

PMID- 11249668
TI  - Retroviral cell targeting vectors.
AB  - The availability of cell targeting vectors is an unalterable requirement for in
      vivo gene therapy trials. This review will describe the different strategies
      developed over the past few years in order to target retroviral vectors to
      preselected human cell types by genetic modification of the envelope (Env)
      proteins. Current targeting concepts include the substitution of the complete Env
      protein as well as the incorporation of new receptor binding domains into the Env
      protein. These approaches are aimed at altering the host range of vectors with a
      natural tropism for non-human cells to specific human cell types, or achieving
      tissue-specificity for vectors that would naturally infect a wide spectrum of
      human cell types. Targeting concepts and efficient targeting vectors with
      potential for clinical trials will be described, and their advantages and
      disadvantages will be discussed.

PMID- 11249669
TI  - Gene transfer with herpes simplex vectors.
AB  - In developing any viral gene delivery vector there are two fundamental problems
      which need to be addressed. Firstly, replication disabled vectors which will be
      safe for clinical use must be constructed, and secondly, strategies for obtaining
      appropriate transgene expression in vector transduced cells must be devised. In
      this review, the progress which has been made in developing herpes simplex virus
      (HSV)-based gene delivery vectors is discussed, as are the experimental results
      which have been obtained using these vectors for gene delivery in tissue culture
      cells and animal models.

PMID- 11249670
TI  - Molecular genetic analysis of herpesviruses and their potential use as vectors
      for gene therapy applications.
AB  - Molecular genetic experiments with large human herpesviruses have provided a
      means whereby large heterologous DNA fragments can be cloned, propagated and
      established in cells permissive for infection with herpesviruses. Some of these
      cells include neuronal cells and B-lymphocytes infected with herpes simplex virus
      (HSV) and Epstein-Barr virus (EBV), respectively as well as human T-lymphocytes
      with herpesvirus saimiri. These large DNA viruses have the potential to deliver
      fragments of human heterologous DNA > 150 kbp to specific cells. Additionally,
      EBV recombinants can maintain these large pieces of DNA in the infected B-cells
      as episomal DNA. The maintenance of these episomes requires a specific EBV
      nuclear protein, EBNA1, constitutively expressed during infection with EBV.
      Additionally, these vectors can be used for transfection, where large amounts of
      protein can be generated transiently in vitro. Herpesvirus amplicon systems are
      also being used to package pieces of DNA > 150 kbp and to infect cells that can
      stably maintain DNA as episomes. Moreover, other herpesvirus vector systems can
      be utilized as a source for the propagation of specific DNA fragments of
      interest, including wild-type genes to correct genetic defects in human cells.
      Other herpesvirus systems include defective infectious single cycle (DISC-HSV)
      mutants of HSV, which are now undergoing trials for the treatment of genital
      herpesvirus infections and certain types of cancers. The use of herpesviruses as
      an agent to deliver heterologous gene products has the potential to make a
      significant difference to the development of therapeutic approaches to human
      diseases.

PMID- 11249671
TI  - Technology evaluation: CRIB (CNTF delivery) CytoTherapeutics Inc.
AB  - To achieve continuous, site-specific delivery of therapeutic molecules to the
      central nervous system (CNS), a new therapeutic approach was developed combining
      in vitro gene transfer with a new delivery device. Xenogenic cells genetically
      modified to secrete specific bioactive substances were encapsulated into polymer
      based fibers. A semipermeable membrane allows for passage of nutrients and cell
      released therapeutic agents, but restricts inward diffusion of larger molecules
      and cells of the host's immune system, thus facilitating xenograft survival. This
      novel technique was successfully tested for the in vitro and in vivo delivery of
      various therapeutic agents, including neurotrophic factors, neurotransmitters and
      hormones. Phase I clinical trials were reported for the treatment of amyotrophic
      lateral sclerosis (ALS) and chronic cancer pain.

PMID- 11249672
TI  - Technology evaluation: StealthVector (HIV) Enzo.
AB  - Efficient inhibition of human immunodeficiency virus-1 (HIV-1) replication with
      intracellularly expressed antiviral genes would be an important step toward
      clinical gene therapy for HIV-1 disease. Enzo Biochem is investigating and
      developing antisense genes as a potential gene therapy approach against a variety
      of conditions including acquired immunodeficiency syndrome (AIDS), cancer and
      hepatitis. The subsidiary of Enzo Biochem, Enzo Therapeutics, utilized its
      StealthVector technology and initiated phase I trials in July 1998
      [291511,307156]. StealthVector, which is comprised of independent antisense
      sequences directed against two functional HIV-1 regions, is involved in
      regulation of gene expression soon after HIV infection, transactivation response
      (TAR) and tat/rev. StealthVector localizes primarily in the cell nucleus, where
      it could be most effective in inhibiting viral growth.

PMID- 11249673
TI  - The polyepitope approach to DNA vaccination.
AB  - The identification of the epitope as the smallest immunogenic subunit derived
      from antigenic proteins has promoted the development of epitope-based vaccines.
      These prevent the danger of administering whole proteins or genes that have
      unknown and possibly dangerous properties. Recent data suggest that DNA encoded
      epitopes in synthetic constructs can be processed and presented to CD8+ T
      lymphocytes despite unnatural flanking amino acid sequences. This has allowed the
      development of polyepitope vaccines for cancer and infectious disease which
      induce multiple cytotoxic T-lymphocyte responses. The resultant immunity may be
      restricted to various HLA alleles and targeted to numerous antigens to avoid
      escape from immune detection by antigen loss variants. This review will describe
      the background of epitope and polyepitope-based vaccination strategies and the
      more recent results that confirm the potential of DNA encoded polyepitope
      vaccines. Future directions that may aid the design of more effective
      polyepitopes will also be discussed.

PMID- 11249674
TI  - Immunotherapy-based treatment strategies for malignant mesothelioma.
AB  - Malignant mesothelioma (MM) is a tumor of the pleura with an etiology that has
      been strongly linked to previous asbestos exposure. It is an almost universally
      fatal disease, regardless of tumor stage at the time of diagnosis. Current
      treatment modalities include surgery, chemotherapy and radiation therapy,
      although in some clinical trials none of these modalities have proven to be
      superior to no treatment at all. Knowledge of the tumor biology and immunology of
      this disease is insufficient, although several studies suggest feasibility and
      success for immunotherapeutic strategies. In this article, we review previous
      work and describe novel therapeutic approaches utilizing biological response
      modification for MM.

PMID- 11249675
TI  - Technology evaluation: DISC.
AB  - Cantab is developing its DISC technology as a potential gene therapy product for
      cancer (DISC-Onc) and neurological and blood disorders (DISC-GT). Clinical trials
      are expected to commence in early 1999 [296831]. The DISC technology utilizes a
      herpes virus that has had a gene removed to prevent it from replicating [250526].
      Phase I trials in leukemia were scheduled to commence in 1998 [250526], however,
      it was decided that although DISC-Onc is capable of carrying genes into leukemic
      cells, the levels of immunomodulator genes did not meet the target initially set
      for the commencement of trials. Hence, Cantab turned its attention to other
      cancers, and hoped to identify an alternative target for phase I trials in the
      first half of 1998 [279798]. Additional preclinical work using a murine version
      of the lead construct produced a significant therapeutic effect in animal tumor
      models [289716]. DISC-Onc is envisaged to deliver immunogenic genes such as
      cytokine or stimulatory protein genes [275129]. Cantab, in collaboration with
      Nottingham Trent University and Birmingham University, has shown that the DISC
      Onc has delivered genes effectively to human colorectal, gastric and ovarian
      cancer tumors. Transfection rates have been shown to be favorable and have been
      proven to be at least as good as, if not better than, other vectors [279798].
      Also, DISC-Onc carrying a functional GM-CSF, has antitumor activity in mouse
      models of renal cancer and leukemia [250526], [261768]. The DISC Neurology
      technology (DISC-GT), for gene therapy of neurological disease, is being
      developed in collaboration with Cambridge University, and enables HSV-driven long
      term gene expression in nerve cells [279798].

PMID- 11249676
TI  - Technology evaluation: naked DNA.
AB  - Vical and Merck are investigating vaccines against hepatitis B which use Vical's
      patented naked DNA technology. Both therapeutic and prophylactic vaccines are
      under development [177132], [268397]. The technology, and subsequent
      collaboration, stems from the observation by Vical that by directly injecting
      exogenous cDNA into muscle tissue, protein is expressed which gives rise to a
      strong immune response and protective immunity [163222].

PMID- 11249677
TI  - Technology evaluation: HIVAC-1e.
AB  - Bristol-Myers Squibb is developing a vaccine, HIVAC-1e, comprised of a
      recombinant vaccinia virus expressing the HIV-1 gp160 envelope glycoprotein. The
      vaccine has potential for the treatment of HIV and other viral infections and has
      entered phase I trials [135333]. In an initial phase I trial, 11 vaccinia-naive
      volunteers were vaccinated with HIVAC-1e, followed by a booster with baculovirus
      derived gp160 (VaxSyn). Two weeks after boosting, all 11 volunteers developed HIV
      1 specific IgG, with titers of 1:40 to 1:1280 [195287]. Using the same strategy
      in 29 vaccinia-naive volunteers, priming with HIVAC-1e was demonstrated as a key
      determinant of the epitope specificity and magnitude of antibody responses to
      gp160 [195278].

PMID- 11249678
TI  - Multivalent minigene vaccines against infectious disease.

PMID- 11249679
TI  - The potential use of DNA vaccines for neonatal immunization.

PMID- 11249680
TI  - DNA vaccines against tuberculosis.
AB  - Application of the DNA vaccine approach to tuberculosis in laboratory animals is
      helping to clarify the immunological mechanisms underlying protective immunity.
      Unexpectedly, it has also indicated clear potential for clinical application.
      This review looks at the implication of recent advances for the development of
      practical TB vaccines.

PMID- 11249681
TI  - Cytokine gene-engineered vaccines.
AB  - Cytokines modulate immune reactivity and have therefore been used to build cancer
      vaccines. Experimental vaccination of rodents and humans with cytokine-gene
      engineered tumor cells, fusion proteins between cytokines and tumor antigens, and
      their DNA have been shown to induce a significant immune memory, even against
      poorly immunogenic tumors. This immune memory can prevent tumor growth and cure
      initial metastases, but is poorly effective against established tumors. To date
      clinical trials have been confined to patients with advanced tumors; so far they
      suggest that this approach is safe.

PMID- 11249682
TI  - DNA vaccines: a role for liposomes.
AB  - Vaccination with attenuated or killed microbes, purified or recombinant subunit
      proteins and synthetic peptides is often hampered by toxicity, the presence of
      infectious agents, weak immune responses and prohibiting costs, especially in the
      developing world. Such problems may be circumvented by genetic immunization,
      which, by the use of plasmid DNA encoding antigens from bacteria, viruses,
      protozoa and cancers leads to protective humoral and cell-mediated immunity. This
      review deals with the background and progress made so far with DNA vaccines and
      evaluates the role of liposomes in their optimization.

PMID- 11249684
TI  - B7-1 gene-modified tumor cell vaccines.

PMID- 11249683
TI  - Development of multicomponent DNA vaccination strategies against HIV.

PMID- 11249685
TI  - The next generation of vaccines for the treatment of cancer.

PMID- 11249686
TI  - Emerging concepts in GM-CSF gene-transduced tumor vaccines for human prostate
      cancer.

PMID- 11249687
TI  - The use of dendritic cells for cancer vaccination.
AB  - Dendritic cells (DC) are the most potent antigen presenting cells (APC) and the
      only ones capable of presenting novel antigens to naive T-cells. Large numbers of
      DC can be generated in vitro in the presence of appropriate cytokine cocktails
      using either adherent peripheral blood mononuclear cells (PBMC) or CD34+
      precursors. More than 20 preclinical studies have demonstrated the effectiveness
      of antigen-loaded DC to mediate antitumor immune responses. Three clinical trials
      have been reported to date that show DC as a promising tool for the immunotherapy
      of cancer. However, completion and analysis of randomized trials to establish the
      appropriate antigen(s), adjuvant(s), dose, route and schedule will be crucial.
      Future DC-based therapies will include genetic modification of DC, the use of
      CD34+ precursors, direct delivery of DC to tumors, and application of tumor
      lysates or apoptotic cells as sources of additional, as yet undefined, antigens.

PMID- 11249688
TI  - Molecular vaccines: delivering on the promise.

PMID- 11249689
TI  - Papillomavirus virus-like particles as anticancer vaccines.
AB  - Papillomavirus virus-like particles (VLPs) are empty, non-replicative, non
      infectious particles that retain conformationally correct epitopes for the
      generation of antibody responses to the viral capsid proteins. Chimeric human
      papillomavirus (HPV) virus-like particles incorporating non-structural virus
      proteins offer an exciting approach for combined prophylactic and therapeutic
      vaccines against HPV-induced lesions. Both HPV VLPs and chimeric VLPs can induce
      potent humoral and cellular immune responses when injected into mice, leading to
      the generation of virus-neutralizing antibodies, priming of CD8+ T-cells and
      activation of cytotoxic T-cell effector functions. This review summarizes recent
      advances in the production of chimeric VLPs, the immune response elicited by VLPs
      and chimeric VLPs, and their ability to generate strong protective and
      therapeutic antitumor immune responses.

PMID- 11249690
TI  - Adoptive cellular immunotherapy of cancer.

PMID- 11249691
TI  - MUC1 and breast cancer.
AB  - The development of an effective immunotherapeutic approach to cancer is now a
      major focus of research, and despite impressive progress over the last 10 years
      there are still many hurdles to overcome to elicit an effective immune response
      which will totally eradicate the cancer. Mucins (MUC1) have attracted interest as
      potential targets for immunotherapy of cancers of breast, pancreas, ovary and
      others, and we have demonstrated that mannan, a polymannose carbohydrate is an
      effective carrier for MUC1 in eliciting a cellular immune response. Several
      clinical trials are in progress to evaluate the immunogenicity of MUC1 and its
      suitability as to use for immunotherapy/vaccine for breast cancer.

PMID- 11249692
TI  - Interaction of viruses with annexins: a potential therapeutic target?
AB  - This review elaborates on the known interactions of annexins with some viral
      pathogens of man. The best documented interactions are those between human
      cytomegalovirus and annexin II, and hepatitis B virus and annexin V. The review
      starts with a description of some structural considerations and potential
      functions of these annexins before going into a more detailed analysis of the
      viral interactions themselves. Finally, some questions relating to the
      suitability of these interactions as a drug target are touched upon.

PMID- 11249693
TI  - RWJ-270201 BioCryst Pharmaceuticals/Johnson & Johnson.
AB  - RWJ-270201, the lead compound in a series of influenza neuraminidase inhibitors,
      is under development by BioCryst for the potential treatment of influenza
      [214908], [337716]. Phase III trials commenced in North America and Europe in
      February 2000 [355053]. Phase II studies were performed to test the effectiveness
      of RWJ-270201 at reducing viral titers in infected patients. Data showed that the
      compound was well tolerated and produced statistically significant reductions in
      viral titers [337716]. Under a worldwide influenza collaboration formed in
      September 1998, two subsidiaries of Johnson & Johnson, the RW Johnson
      Pharmaceutical Research Institute and Ortho McNeil, have received exclusive
      worldwide rights to RWJ-270201 [298487].

PMID- 11249694
TI  - VP-14637 ViroPharma.
AB  - VP-14637 is the lead compound in a series of low molecular weight viral
      replication inhibitors which are under preclinical investigation by ViroPharma
      for the potential treatment of RSV infection [322651]. Phase I trials designed to
      evaluate the safety and pharmacokinetic prpfile of VR-14637 in healthy human
      volunteers have begun [385870]. VP-14637 is most active against pneumoviruses and
      the available data suggest that it is an inhibitor of RSV viral fusion activity
      [363716], [361097].

PMID- 11249695
TI  - Targeting remodeling in respiratory inflammation.
AB  - Chronic asthma causes considerable morbidity, mortality and utilization of
      healthcare resources. The fact that asthma still causes such problems despite the
      widespread use of anti-inflammatory treatment suggests that new approaches are
      needed. Airways in chronic asthma are characterized by considerable remodeling
      which affects a number of structures, particularly airway smooth muscle and
      changes in airway smooth muscle thickness may be one of the most important
      determinants of bronchial hyperresponsiveness. Here we suggest new approaches
      that might be used to target smooth muscle remodeling in asthma.

PMID- 11249696
TI  - Interleukin-5: a drug target for allergic diseases.
AB  - There is a large body of evidence that eosinophils are a key component of the
      allergic response in asthma. Interleukin (IL) 5 is uniquely involved in the
      production of eosinophils, and with a variety of other cytokines and factors
      controls their activation, localization and survival. Thus, IL-5 is an important
      drug target for new anti-asthmatics. The routes to drug discovery are based on
      screens for inhibitors of IL-5 production, ligand antagonists, control of
      receptor expression and receptor activation. In this review, we will discuss
      specific targets and screening assays with examples of some of the compounds in
      development.

PMID- 11249697
TI  - Altering the Th1/Th2 balance as a therapeutic strategy in asthmatic diseases.
AB  - The identification of distinct T helper (Th)-cell subsets that differ in cytokine
      production and effector functions not only provides a framework for normal immune
      responses to infection and injury, but also for many disease processes. Studies
      in both humans and animals indicate that airway inflammation in allergic asthma
      is orchestrated by CD4+ Th2-cells that secrete the cytokines IL-4, IL-5 and IL
      13. Many studies also suggest that IFN gamma, secreted by Th1-cells, suppresses
      the development and effector functions of Th2-cells. Cross-regulation of Th1/Th2
      responses has been demonstrated in many experimental systems including models of
      allergic inflammation/asthma. A challenging concept that has evolved as a result
      is the use of therapeutic modalities that will modulate the Th1/Th2 balance in
      asthma without deleterious side effects. In the clinical trial arena, the unmet
      challenging goal remains to convert the concept of Th1/Th2 balance modulation,
      without deleterious side effects, into clinical practice for the management of
      asthmatic disease.

PMID- 11249698
TI  - PNU-142731A Pharmacia.
AB  - Pharmacia is developing PNU-142731A, a potential lead compound as a treatment for
      asthma [294718]. It is in phase I clinical trials. PNU-142731A is a potent
      inhibitor of eosinophilic lung inflammation in rodents, and shows a good
      bioavailability profile in animals; the mechanism of action is being
      investigated. Unlike the original compound PNU-104067F, PNU-142731A does not give
      rise to gall bladder toxicity [295987], [298023].

PMID- 11249699
TI  - Acute stroke therapy: translating preclinical neuroprotection to therapeutic
      reality.

PMID- 11249700
TI  - Role of antiplatelet agents in stroke.

PMID- 11249701
TI  - Lanoteplase Genetics Institute.
AB  - Lanoteplase, a modified form of a tissue plasminogen activator (t-PA) lacking
      fibronectin finger-like and epidermal growth factor domains, was developed by the
      Genetics Institute for the potential treatment of thromboembolic disorders.
      Suntory, the Japanese licensee, has filed an NDA in Japan for the treatment of
      acute myocardial infarction (MI) [301222]. It was also licensed to Bristol-Myers
      Squibb (BMS) for worldwide development (excluding Japan, China, South Korea and
      Taiwan) [178225]. BMS conducted phase III trials for acute MI [272490] but
      discontinued development and returned the license to Genetics Institute during
      1999 [359688]. In February 1999, Lehman Brothers predicted the drug had a 60%
      probability of reaching market, with an estimated first launch date in 2000. The
      analysts predicted peak sales would occur in 2006, with peak sales of $200
      million in the US and US $100 million in the rest of the world at that time
      [319225].

PMID- 11249702
TI  - MS-325 EPIX.
AB  - EPIX is developing MS-325 (AngioMARK), an intravascular magnetic resonance
      contrast agent for use in the imaging of blood vessels and blood flow in patients
      with cardiovascular disease, including peripheral vascular disease (PVD). In June
      1999, EPIX and Mallinckrodt began phase III trials of MS-325 for the detection of
      aortoiliac occlusive disease in patients with PVD or abdominal aortic aneurysm
      [328640]. NDAs for the peripheral and cardiac applications were expected in 1999
      and 2000, respectively [275240], [325717]. MS-325 has also shown promise in
      demonstrating the presence of microscopic muscular dystrophy, as well as
      monitoring the effects of gene therapy in a mouse model of the disease [360974].
      MS-325 is a stable complex of gadolinium and an organic chelating agent. It
      resembles approved agents in terms of stability, safety and elimination profile,
      but possesses novel chemical groups which allow it to bind reversibly to albumin.
      This retains the agent in the blood and, via a patented biophysical phenomenon,
      enhances the magnetic properties of the gadolinium ion approximately ten-fold.

PMID- 11249703
TI  - Recent advances in atypical antipsychotics.

PMID- 11249704
TI  - Dexanabinol Pharmos.
AB  - Dexanabinol is a non-psychotropic cannabinoid NMDA receptor antagonist under
      development by Pharmos Corp for the potential treatment of cerebral ischemia,
      glaucoma, Alzheimer's disease, cardiac failure, head injury and multiple
      sclerosis (MS) [311522]; it is in phase III trials for traumatic brain injury
      (TBI) [388709]. Dexanabinol was licensed to Pharmos for development from its
      originator, the Hebrew University of Jerusalem [180441]. Pharmos is seeking to
      enter into a strategic agreement with another company to develop and
      commercialize dexanabinol [317369]. Unlike its enantiomer, HU-210 (Yissum
      Research Development Co), dexanabinol does not interact with cannabinoid
      receptors [223330]. It has also exhibited more effective antioxidant and anti
      inflammatory properties than MK-801 (dizocilpine; Merck & Co Inc) [167980],
      [168212]. In addition, dexanabinol is generally well tolerated and appears
      toxicologically safe [170116]. Pharmos has been awarded a Small Business
      Innovation Research grant from the National Institutes of Health (NIH) National
      Institute of Neurological Disorders and Stroke, Division of Stroke and Trauma.
      The grant covers the development of new prodrugs and novel formulations of
      dexanabinol and will support additional study of dexanabinol compounds for
      various indications. The prodrugs being studied are part of the group of
      compounds that include dexanabinol [247958]. A Notice of Allowance was received
      in March 1999 on a patent covering the use of the drug in the treatment of MS
      [324163]. The use of dexanabinol and its derivatives to treat MS is described in
      US-05932610 [358503]. An oral formulation of dexanabinol is claimed in US
      05891468. Dexanabinol analogs with special utility in acute and chronic pain are
      claimed in US-04876276, while dexanabinol analogs for neuroprotection are claimed
      in US-06096740. Pharmos estimates that the worldwide market for dexanabinol in
      the treatment of severe head trauma may reach $1 billion per year [319244].

PMID- 11249705
TI  - Brasofensine NeuroSearch.
AB  - Brasofensine (NS-2214) is a dopamine reuptake inhibitor under development by
      NeuroSearch for the potential treatment of Parkinson's disease (PD) [178224]. The
      compound entered phase II trials in Denmark in November 1996, and phase I trials
      in the US in January 1996 [195505], [206604]. Bristol-Myers Squibb (BMS) had been
      codeveloping the compound until June 1999, when it decided to withdraw from the
      collaboration due to financial restraints of further regulatory requirements
      (such as additional toxicology documentation) [318365], [329665]. NeuroSearch was
      seeking licensing agreements with one or more international pharmaceutical
      companies to accelerate the development and marketing of brasofensine [187758]
      and had plans to meet with new potential partners for discussions concerning
      brasofensine licensing in late 1999 [337221]. A more complete evaluation of the
      effects of brasofensine was anticipated to be obtained through controlled trials,
      of at least 3 months duration, comparing it with a placebo and the marketed anti
      Parkinson's drug, L-DOPA [317406]. In addition, further animal (monkey) tests
      were planned in order to document the safety of the drug in long-term treatment.
      These studies were expected to be discussed with the US FDA in October 1999 and,
      if satisfactory, the 3-month clinical trials were planned to commence in mid-2000
      [337221]. At a meeting with the FDA during 1999, NeuroSearch presented plans for
      developing brasofensine alone. These were found to be satisfactory on condition
      that further preclinical studies were performed prior to any more clinical
      development [371542]. In August 2000, Lehman Brothers predicted worldwide sales
      of US $45 million in 2002 and US $175 million in 2003 [389229]. In February 1999,
      Lehman Brothers predicted the drug had a 35% probability of reaching market, with
      an estimated first launch date in 2002. The analysts predicted peak sales would
      occur in 2009, with sales of $250 million at that time [319225].

PMID- 11249707
TI  - Overview. Cancer drug discovery: pathway promise or covalent certainty for drug
      effect--quo vadis?

PMID- 11249706
TI  - Overview. A new discovery phase for antitumor drugs?

PMID- 11249708
TI  - Bexarotene ligand pharmaceuticals.
AB  - Bexarotene (LGD-1069), from Ligand, was the first retinoid X receptor (RXR)
      selective, antitumor retinoid to enter clinical trials. The company launched the
      drug for the treatment of cutaneous T-cell lymphoma (CTCL), as Targretin
      capsules, in the US in January 2000 [359023]. The company filed an NDA for
      Targretin capsules in June 1999, and for topical gel in December 1999 [329011],
      [349982] specifically for once-daily oral administration for the treatment of
      patients with early-stage CTCL who have not tolerated other therapies, patients
      with refractory or persistent early stage CTCL and patients with refractory
      advanced stage CTCL. The FDA approved Targretin capsules at the end of December
      1999 for once-daily oral treatment of all stages of CTCL in patients refractory
      to at least one prior systemic therapy, at an initial dose of 300 mg/m2/day.
      After an NDA was submitted in December 1999 for Targretin gel, the drug received
      Priority Review status for use as a treatment of cutaneous lesions in patients
      with stage IA, IB or IIA CTCL [354836]. The FDA issued an approvable letter in
      June 2000, and granted marketing clearance for CTCL in the same month [370687],
      [372768], [372769], [373279]. Ligand had received Orphan Drug designation for
      this indication [329011]. At the request of the FDA, Ligand agreed to carry out
      certain post-approval phase IV and pharmacokinetic studies [351604]. The company
      filed an MAA with the EMEA for Targretin Capsules to treat lymphoma in November
      1999 [348944]. The NDA for Targretin gel is based on a multicenter phase III
      trial that was conducted in the US, Canada, Europe and Australia involving 50
      patients and a multicenter phase I/II clinical program involving 67 patients.
      Targretin gel was evaluated for the treatment of patients with early stage CTCL
      (IA-IIA) who were refractory to, intolerant to, or reached a response plateau for
      at least 6 months on at least two prior therapies. Efficacy results exceeded the
      protocol-defined response target rates; side effects were primarily limited to
      local skin reactions [349982]. Ligand has worldwide rights to market bexarotene
      capsules, and will market the drug in the US, Canada and selected European
      markets. In Spain, Portugal, Greece and Central and South America, Ferrer
      Internacional will market and distribute the drug. As of December 1999, Ligand
      was seeking additional distribution partners for select European and Asian
      markets [351604]. In January 2000, Alfa Wassermann signed an agreement with
      Ligand to exclusively market and distribute Targretin gel and capsules in Italy.
      Alfa paid US $0.75 million on signing with additional amounts up to an aggregate
      total of US $1.0 million on achievement of certain registration milestones, which
      are expected to be met in 2000 [351882].

PMID- 11249709
TI  - Gd-Tex Pharmacyclics Inc.
AB  - Pharmacyclics is developing Gd-Tex (gadolinium texaphyrin) as a radiosensitizer
      for the potential treatment of various cancers including brain metastases and
      primary brain tumors, pancreatic tumors, lung tumors and pediatric cancers
      [196711], [348919]. The compound entered phase III pivotal trials for brain
      metastases in September 1998 [323929]. Phase I clinical trials for the treatment
      of primary brain tumors and pancreatic cancer have been initiated while several
      trials in other cancer types are in the planning stages [367716]. In September
      1998, Pharmacyclics announced the initiation of a pivotal phase III trial for the
      treatment of patients with brain metastases. This multicenter trial originally
      included 30 sites in the US, Canada and Europe, and was expected to enroll 425
      patients. The FDA agreed that this trial qualified for Fast Track review if
      efficacy end-points are met [301265]. By October 2000, nearly all 450 patients in
      50 sites had been completed [375959], [387023]. In September 2000, Pharmacyclics
      and the National Cancer Institute (NCI) initiated two phase I trials of Gd-Tex.
      The first was to determine the safety of two different dosing regimens of the
      drug during preoperative radiotherapy after induction chemotherapy in patients
      with stage IIA non-small cell lung cancer (NSCLC). The second would examine the
      use of Gd-Tex in combination with stereotactic Gamma Knife radiosurgery in
      patients with primary brain tumors known as glioblastoma multiforme [381561]. A
      phase Ib/II trial, for brain metastases, was conducted in America and France, and
      involved over 100 patients. At the ASCO 1998 meeting, interim tumor response data
      were presented for 37 patients. The overall tumor response rate (complete plus
      partial response rate) was 73%. Furthermore, MRI scanning confirmed that Gd-Tex
      accumulated selectively in tumors [287459]. Full results were announced in
      October 1998 at the American Society of Therapeutic Radiology and Oncology.
      Following ten daily injections followed by whole brain radiation, 77.7% of
      patients demonstrated a tumor response defined as greater than 50% reduction in
      tumor volume. Gd-Tex was well tolerated, and liver enzyme elevation was the dose
      limiting effect, which was reversible. Death due to tumor progression was seen in
      15% of the Gd-Tex group as opposed to 35% in the control group [302872]. In
      November 1999, Pharmacyclics commenced a phase I trial of Gd-Tex injection,
      sponsored by the NCI, for treating children with intrinsic pontine glioma. The
      goals of the phase I dose-ranging study were to determine the Gd-Tex dose and
      administration schedule that can be safely administered with radiation and to
      evaluate the localization of Gd-Tex in affected tumors using MRI [348035]. In
      March 1997 the Decision Network of the NCI voted to sponsor additional clinical
      indications including adult and pediatric brain tumors, as well as cancers
      involving the lung, head & neck, pancreas and prostrate. Two phase I trials of Gd
      Tex for the treatment of primary brain tumors commenced in August 1998 under a
      CRADA with the NCI [237538], [295592], [348919]. Pharmacyclics is collaborating
      with the NCI under a CRADA in phase I trials in primary brain tumors and
      pancreatic tumors [323929], [323952], [346596]. Analysts expected a filing to
      occur by the end of 1999 or early 2000, with sales in 2001 [303186].

PMID- 11249710
TI  - Recent advances in the analysis of HCV NS5B RNA-dependent RNA polymerase.
AB  - An RNA-dependent RNA polymerase denoted nonstructural protein 5B (NS5B) is the
      central enzyme in replication of the hepatitis C virus genome. Recent advances in
      the biochemical and structural understanding of NS5B include solubilization and
      purification of the full-length enzyme and various truncated forms. In vitro
      conditions for NS5B-catalyzed primer elongation using both homo- and
      heteropolymeric RNA templates were discovered. The crystal structure of the NS5B
      apoenzyme revealed a globular shape unique among polymerases, and implicated new
      structural features important for binding the RNA template and cognate
      ribonucleotide substrates. The crystallographic results also provided a structure
      based framework for biochemical analyses and drug-design efforts. Finally,
      inhibitors of HCV RNA-dependent RNA polymerase have been reported.

PMID- 11249711
TI  - AG-7088 Pfizer.
AB  - Pfizer (formerly Agouron) is developing AG-7088, a peptide aldehyde that targets
      the human rhinovirus (HRV) 3C proteinase enzyme and has potential for the
      treatment of the common cold. A phase II efficacy study has been completed in
      healthy patients infected with the virus [318668] and in November 1999, Agouron
      initiated a large, double-blind, placebo-controlled trial in the US, in
      individuals within 36 h of experiencing cold symptoms [346362]. AG-7088 is
      derived from AG-6084, the development of which has been discontinued. In order to
      develop human rhinovirus 3C protease inhibitors with improved pharmacological
      properties, Agouron replaced the backbone amide moiety of the series which
      yielded AG-6084, with a ketomethylene isostere. Such compounds displayed slightly
      reduced anti-3CP inhibitory activity, but improved antiviral properties, due to
      increased cell membrane permeability [324627]. Compounds in which P1 lactam
      moieties were incorporated in lieu of an L-glutamine residue displayed
      significantly increased 3CP inhibition activity and improved antirhinoviral
      properties relative to the corresponding molecules. Of this series, AG-7088 was
      the most potent inhibitor [324635]. In May 2000, Merrill Lynch predicted that
      phase III trials would begin in the first half of 2000 and that US filing would
      take place in the second half of 2001 [375962].

PMID- 11249712
TI  - Pleconaril Sanofi Synthelabo/ViroPharma.
AB  - Pleconaril is an oral antiviral agent being developed by ViroPharma and Sanofi
      Synthelabo (formerly Sterling Winthrop) for the potential treatment of several
      picornavirus-induced infections, including respiratory diseases and viral
      meningitis. A number of phase III clinical trials have been completed, and
      several others are ongoing [319499], [343187], [346302], [359231]. In early 1999,
      an NDA filing for viral meningitis was expected by the end of 1999 [313588],
      [319499]. However, an NDA had not been filed by February 2000 and, at this time,
      filing in the US was expected in 2000 for viral meningitis and 2001 for viral
      respiratory syndrome, while in Europe filing was expected in 2001 and 2002 for
      these indications, respectively [359231]. In July 2000, Salomon Smith Barney
      predicted a launch date of 2002 [387350]. In October 1999, Lehman Brothers
      predicted a 70% chance of the product reaching the market, with a possible launch
      date anticipated for 2001 and potential peak sales of US$50 million in 2009
      [346267].

PMID- 11249713
TI  - Clevudine University of Georgia/Abbott/Bukwang/Triangle/Yale University.
AB  - The pyrimidine analog, clevudine (L-FMAU: 2'-fluoro-5-methyl-beta-L
      arabinofuranosyluridine) is a potent antihepatitis B virus (HBV) and anti-Epstein
      Barr virus (EBV) agent, discovered by researchers at the University of Georgia,
      in collaboration with Yale University and Bukwang. Bukwang transferred its
      technology to Triangle Pharmaceuticals in 1998 together with a license to develop
      clevudine worldwide except Korea [279649], [281942]. In June 1999, Triangle and
      Abbott Laboratories entered into a strategic alliance to copromote antiviral
      products including L-FMAU [326798]. In September 2000, Triangle Pharmaceuticals
      Inc initiated a 30-day phase I/II evaluation of clevudine in HBV-infected
      patients [381755]. Clevudine is a much less toxic derivative of the toxic agent P
      D-FMAU. The mechanism of action of clevudine is not yet clear, but the agent
      induces a rapid decrease in HBV nucleic acid as doses increase from 0.3 to 10
      mg/kg [319145]. It is believed that the target for clevudine lies in the viral
      replication mechanism. Clevudine is phosphorylated to the triphosphate form
      intracellularly. This is removed slowly from the cells, thus exerting a sustained
      inhibitory antiviral activity [178173], [320720], [320721].

PMID- 11249714
TI  - Chemokines and chemokine receptors in pulmonary diseases.

PMID- 11249715
TI  - The eotaxins in asthma and allergic inflammation: implications for therapy.
AB  - Evidence is emerging for an important role for the CC chemokines, particularly
      the eotaxins, in the pathogenesis of asthmatic and allergic inflammation. This
      article reviews the evidence for this involvement and describes new approaches to
      therapeutics that are evolving as a result.

PMID- 11249716
TI  - Pharmacological therapy for acute stroke.

PMID- 11249717
TI  - Cariporide Aventis.
AB  - Cariporide is a sodium/hydrogen ion exchange inhibitor under development by
      Aventis Pharma, formerly Hoechst Marion Roussel (HMR), as a potential treatment
      for myocardial infarction (MI), ischemic damage due to angioplasty and
      reperfusion following thrombolysis. It is in phase II/III trials [221118].
      Cariporide inhibits the interchange of sodium ions and protons in myocardial
      cells during unstable angina or MI when cells metabolize anerobically. This
      prevents lactic acid production and an increase in calcium levels which causes
      cardiac arrhythmias and heart tissue death [253616]. Approval filings in the US
      and EU had been scheduled for the second half of 1999 [309323]. In 1998, HMR
      expected that the drug would be launched in 2000, and would have a potential
      market in excess of DM 750 million [288651]. By May 2000, however, the launch
      date had been revised for between 2003 and 2004 [370971], [379336]. Aventis is
      expecting peak sales to be around $400 million [333420]. In March 1999, HMR
      reported that trials for MI had been suspended after results from the phase III
      GUARDIAN trial did not achieve statistical significance [353173]. In August 2000,
      however, a phase II trial in patients with acute MI was underway [379051]. A
      phase III trial in patients undergoing coronary artery bypass grafting (CABG) was
      expected to begin in early 2000 after the results of ongoing dose-optimization
      studies in CABG patients are known. As of May 2000, however, this trial had not
      begun, although based on promising CABG-related results of the GUARDIAN trial,
      the phase III trial in this indication is expected to begin in the first half of
      2001 [370971]. There were also plans for the initiation of European phase II
      trials in acute MI patients; similar phase II trials are ongoing in Japan. In
      September 2000, Merrill Lynch predicated launch in 2003 [383742]. In February
      1999, Lehman Brothers predicted a 70% probability that cariporide would reach
      market in the US/Europe and 50% probability that it would reach the Japanese
      market. They also predicted a US/European launch in 2000 with peak sales of $400
      million in 2008 and a Japanese launch in 2002 with peak sales of $100 million
      [319225].

PMID- 11249718
TI  - Edaravone Mitsubishi-Tokyo.
AB  - Mitsubishi-Tokyo (formerly Mitsubishi Chemical) is developing edaravone
      (norphenazone), a free radical scavenger, for the potential treatment of
      cardiovascular disease, cerebrovascular ischemia and cerebral edema. By February
      2000, edaravone had been filed in Japan for the treatment of acute brain
      infarction, and was in phase III trials for subarachnoid hemorrhage [365460]. The
      compound blocks the action of the lipoperoxide, 15-HPETE, which normally
      increases with age and may be associated with neurodegeneration.

PMID- 11249719
TI  - Methylphenylethynylpyridine (MPEP) Novartis.
AB  - SIBIA and Novartis are investigating the use of excitatory amino acid agonists
      and antagonists for the metabotropic receptor and the ionotropic receptors AMPA
      and NMDA. Preliminary experiments indicate they may have potential in the
      treatment of epilepsy, stroke, anxiety, pain and neurodegenerative disease.
      Methylphenylethynylpyridine (MPEP) is the lead compound in the series [347212].
      Other compounds in the series that arose from the collaboration were SIB-1893,
      and its equipotent analog, SIB-1757, both of which are subtype-selective, potent
      antagonists of mGluR5. Chemical derivation of SIB-1893 resulted in the discovery
      of MPEP, a selective, systemically active noncompetitive mGluR5 antagonist.
      Studies using these agents have yielded data to support the involvement of mGluR5
      in inflammatory mechanical hyperalgesia [311829], [311828], [311823], [311880],
      [319655]. MPEP is the most potent of these compounds with an IC50 value of 12 nM
      for inhibition of quisqualate-stimulated phosphoinositide hydrolysis in
      recombinant human mGluR5a-expressing cells. MPEP exhibited no cross reactivity
      with mGluR1 and other mGluRs, or against representative NMDA, AMPA and kainate
      receptors up to concentrations of 100 microM. The compound, administered orally
      (100 mg/kg) produced a 70% reversal of mechanical hyperalgesia in the Freund's
      complete adjuvant model of inflammatory pain [319261]. By October 1999,
      investigations with SIB-1757 and SIB-1893 had been discontinued in favor of MPEP
      [347212].

PMID- 11249720
TI  - Potential clinical uses of neuroactive steroids.
AB  - Neuroactive steroids rapidly modulate gamma-aminobutyric acid (GABA) and
      glutamate receptors. GABA-enhancing steroids have potential clinical utility as
      anesthetics, hypnotics, anticonvulsants and anxiolytics. Furthermore, GABAergic
      neurosteroids may participate in regulating mood and the effects of alcohol on
      the nervous system, suggesting a potential role in major psychiatric disorders.
      Neuroactive steroids that alter the function of glutamate receptors could be
      useful for treating neurodegenerative disorders, and as cognitive enhancers.
      Recent progress in developing water-soluble steroids and steroids with enhanced
      oral efficacy foster optimism that certain neuroactive steroids will be developed
      for clinical use.

PMID- 11249722
TI  - Fampridine Acorda Therapeutics.
AB  - Fampridine (EL-970; 4-aminopyridine), a potassium channel blocker, is in phase II
      development by Acorda for the potential treatment of spinal cord injuries and
      multiple sclerosis (MS) [385529]. Originally, Elan was evaluating fampridine for
      the treatment of spinal cord injuries in collaboration with Acorda Therapeutics
      [243393]. The drug was licensed from Rush Medical Center and Elan holds worldwide
      rights with Rush to provide clinical and technical support. Elan has used its
      Intestinal Protective Drug Absorption System (IPDAS) drug delivery system to
      produce Neurelan, which is a controlled-release (twice daily) formulation of
      fampridine [223736]. However, it seems possible that production of Neurelan might
      be taken over by Acorda [381211]. Acorda completed preliminary phase II trials of
      the drug for spinal cord injury (SCI) in 1998 [303023]. In February 2000, the
      company predicted that it would begin the a late-stage phase II trial for chronic
      (long-term) SCI in the first quarter of 2000 [355696], [350955]. The trial, which
      will be double-blind, randomized and placebo-controlled, will enroll 90 people
      with chronic SCI at 10 US rehabilitation centers [355696]. As of July 2000, phase
      II studies for chronic SCI were underway and phase III studies are expected to
      begin in 2001 [376610]. Results presented at the EPHAR '99 congress showed that
      contractions induced by 4-AP in porcine coronary arteries, are likely to depend
      on the neuronal 5-HT, but not on the noradrenaline store in this tissue [334161].

PMID- 11249721
TI  - CP-101606 Pfizer Inc.
AB  - CP-101606 is a potent, selective NMDA receptor (NR2B subunit) antagonist under
      development by Pfizer for its potential as a neuroprotectant in head injury and
      neurodegenerative disease. It is in phase II trials in the US and in phase I in
      Japan for the potential treatment of head injury [267139], [320737], [378812]. As
      of March 2000, CP-101606 had completed US phase I trials successfully and was
      well tolerated with a good safety profile. Results of an open-label study in
      patients treated with CP-101606 (24 to 72 h infusion) following severe head
      trauma showed that 80% of patients had good recovery at the 3-month follow-up
      stage [360864]. In August 2000, Merrill Lynch predicted that the phase II trials
      program could be complete by the end of 2000 with the possibility of a filing
      based on its results if positive [379892]. The drug lacks the amnesic side
      effects of other NMDA receptor antagonists and it has no effects on long-term
      potentiation (LTP) [347642]. According to presenters at the 1999 Society for
      Neuroscience meeting, this may result from a novel activity-dependent or NR2B
      selective mechanism of action [345079]. It is thought to act by inhibiting the
      damaging influx of Ca2+ across neuronal cell membranes following glutamate
      release triggered by tissue injury, e.g., stroke [300847]. CP-101606 prevents
      glutamate-induced toxicity in cultured hippocampal neurons when given during or
      immediately after glutamate perfusion, (IC50 = 11 and 35 nM, respectively). In
      contrast, CP-101606 does not protect against glutamate-induced neurotoxicity in
      cultured cerebellar neurons, up to a dose of 10 microM. These results are
      consistent with CP-101606 being a potent NMDA antagonist, selective for the type
      of NMDA receptor associated with the hippocampus [195435]. CP-101606 is a single
      isomer analog of CP-98113 (Pfizer Inc) [254010]. CP-101581 (Pfizer Inc) is an
      isomer of CP-101606 [254010]. In December 1998, Morgan Stanley Dean Witter
      predicted sales of US $5 million in 2001, rising to US $80 million by 2005
      [315350].

PMID- 11249723
TI  - Lipoxins: novel anti-inflammatory therapeutics?
AB  - Lipoxins (LX) are endogenously produced eicosanoids that promote the resolution
      of inflammation. Here we review the accumulating evidence that LX act as potent
      modulators of leukocyte trafficking in model systems in vitro and in vivo. Of
      particular interest are indications that aspirin-triggered epi-LX and synthetic
      LX combine many of the desirable anti-inflammatory actions of LX with enhanced
      stability and bioavailability. Such synthetic analogs have potential as novel
      therapeutics. Furthermore, the bioactivities of the aspirin triggered LX may
      account for some of the well-documented prostaglandin-independent anti
      inflammatory actions of aspirin.

PMID- 11249725
TI  - Technology evaluation: BLP-25, Biomira Inc.
AB  - Biomira is developing the MUC-1 peptide-based vaccine BLP-25 for the potential
      treatment of cancer. It is in phase II trials for non-small cell lung cancer
      (NSCLC) [335997], [353448], [384703]. The MUC-1 mucin secreted by cancer cells
      has been shown to decrease the activity of certain immune response cells,
      including killer T-cells, and can inhibit the immune T-cell response by > 70%.
      BLP-25 is designed to target an immune response to the MUC-1 mucin that is shown
      by > 90% of common solid tumors. The introduction of IL-2 reverses the T-cell
      suppression caused by MUC-1 mucin, and enhances the cellular immune response >
      100-fold. Biomira has been incorporating IL-2 into a liposomal delivery system
      for BLP-25 [274576]. In late 1998, Biomira entered into a research collaboration
      with Axis Genetics. The collaboration will assess the further potential of
      therapeutic cancer vaccines against MUC-1. Each company has developed a vaccine
      targeting the MUC-1 peptide and Biomira will be evaluating Axis's vaccine in
      preclinical trials [313395]. In December 1996, Biomira signed a licensing
      agreement whereby it was granted the rights to use Dana-Farber Cancer Institute's
      two US patents relating to MUC-1 (based on pioneering work at the Institute on
      the identification of cell-surface molecules that are characteristic of cancer
      cells) for peptide-based cancer vaccines [228101].

PMID- 11249724
TI  - Exisulind Cell Pathways.
AB  - Cell Pathways has developed exisulind (Aptosyn), an oral apoptosis modulator and
      cGMP phosphodiesterase inhibitor, for the potential treatment of several
      oncologic indications including precancerous adenomatous polyposis coli (APC),
      also known as familial adenomatous polyposis (FAP), precancerous sporadic colonic
      polyps, cervical dysplasia and the prevention of tumor recurrence in prostate and
      breast cancer. An NDA filing for the treatment of precancerous APC, for which the
      US FDA designated exisulind a Fast Track product in July 1998, was initially
      expected in March 1999 [291313]. However, in January of the same year the company
      stated that it anticipated a delay in the NDA filing. The decision was based on
      unsatisfactory phase III data [308912], [313124]. In June 1999, the company
      completed analysis of the phase III trial data [328000] and the NDA was submitted
      in August 1999. An NDA was accepted for review by the FDA in October 1999 for the
      treatment of APC [328000], [338007], [344721], after data from three additional
      trials were submitted to the FDA in support of the NDA. At this time phase II/III
      trials were also ongoing for prostate and breast cancer recurrence [287250],
      [326795]. Approval for the indication of FAP had been expected by the end of 2000
      [365737] but in September 2000 the FDA completed its initial review and advised
      Cell Pathways that exisulind will not be approved at this time. Cell Pathways has
      received a 'non-approvable' letter and intends to advise the FDA of its intent to
      amend the NDA and to request a meeting to address the deficiencies in the NDA
      [383249], [383560]. The first of the three additional trials submitted to the FDA
      in October 1999 was a 6-month, open-label trial involving 48 of the patients who
      completed a phase II/III study of exisulind in early 1999. After 6 months of
      treatment with exisulind, 25 patients who had previously been taking placebo
      experienced a 50% reduction in polyp formation. The patients continuing treatment
      with exisulind exhibited a further 50% reduction from their already reduced rate
      of polyp formation [344991]. The second study was an extension study of 11
      patients who participated in a 6-month, open-label, phase I/II, dose-ranging,
      safety and efficacy trial. As of October 1999, these patients were still on
      therapy and had been receiving exisulind for between 36 and 50 months. They had
      all experienced statistically significant reductions in polyp formation rates
      [344991]. The third study was a double-blind, placebo-controlled safety study of
      26 patients. All patients exhibited a trend of reduced new polyp formation when
      compared to placebo. Exisulind was generally well-tolerated by all patients
      during the course of the studies [344991]. In July 2000, Cell Pathways signed a
      marketing and distribution agreement for Canada with Paladin Labs, allowing
      Paladin exclusive rights to commercialize exisulind within Canada [376072]. Also
      in July 2000, Cell Pathways announced that patents covering methods of
      identifying compounds that selectively stimulate apoptosis have been allowed in
      Europe and Japan. The patents describe the mechanism of action of Cell Pathways'
      SAANDs, including exisulind, and use of that knowledge in screening for new drugs
      [374888]. In January 1999, the company received US-05858694 covering the
      mechanism of action of exisulind [311504].

PMID- 11249726
TI  - Web alert. Molecular vaccines for disease prevention and therapy.

PMID- 11249728
TI  - Unraveling the mechanisms by which heat shock proteins activate the immune
      system.
AB  - A role for heat shock proteins in eliciting CD8 cytotoxic T-lymphocyte (CTL)
      responses in the absence of exogenous adjuvants has been documented for some
      time. Only recently, however, has the mechanism by which these molecules are able
      to elicit such responses begun to be elucidated.

PMID- 11249727
TI  - Enhancing vaccines with immune stimulatory CpG DNA.
AB  - Certain vertebrate immune cells have evolved receptors that detect the presence
      of pathogen DNA based on its content of unmethylated CpG dinucleotides in
      particular base contexts. This 'CpG DNA' acts as a 'danger signal', triggering
      protective innate and acquired immune responses. The activity of CpG DNA can be
      mimicked with synthetic oligodeoxynucleotides, which when added to a vaccine
      greatly boost the resulting immune response.

PMID- 11249729
TI  - DNA shuffling and vaccines.
AB  - One challenge of biotechnology is to find ways to optimize enzymes, cytokines,
      vaccines or transgenes in new contexts that are typically not found in nature.
      The approach of DNA shuffling is a test-tube process that takes advantage of
      recombination to generate libraries of chimeric genes, which can then be screened
      to identify the encoded proteins improved in one or more functions. DNA shuffling
      of two or more genes that are structurally similar and homologous in function is
      particularly efficacious in generating large libraries of functionally novel
      molecules. Other directed evolution methods, such as those involving directed or
      random mutagenesis, have several limitations compared to the DNA shuffling
      recombination process. A wide variety of genes have been submitted to DNA
      shuffling, and significant improvements in various functional parameters have
      been obtained. Several examples of the application of DNA shuffling to vaccine
      development, therapeutics and gene therapy are discussed here.

PMID- 11249730
TI  - The B-cell targeted CTA1-DD vaccine adjuvant is highly effective at enhancing
      antibody as well as CTL responses.
AB  - A novel immunomodulating gene-fusion protein, CTA1-DD, has been developed which
      combines the ADP-ribosylating ability of cholera toxin (CT) with a dimer of an Ig
      binding fragment, D, of Staphylococcus aureus protein A. The CTA1-DD adjuvant is
      non-toxic and greatly augmented T-cell-dependent and T-cell-independent responses
      to soluble admixed antigens after systemic as well as mucosal immunizations. CTL
      and antibody responses of all classes were increased by 10- to 100-fold above
      those observed in control mice immunized without adjuvant. CTA1-DD does not
      appear to form immune complexes or bind to soluble Ig following injection, but
      rather it binds directly to B-cells of all isotypes, including naive IgD+ cells.
      No binding was observed to macrophages or dendritic cells, and immunizations in
      Fc gamma R-deficient mice demonstrated unaltered enhancing effects. As shown by
      inactive mutants, the CTA1-DD adjuvant is dependent on ADP-ribosyltransferase
      activity and requires the binding to Ig- via the DD moiety. The enhancing effect
      is associated with enlarged germinal centers, and binding of CTA1-DD to the B
      cells strongly upregulates co-stimulatory molecules and counteracts apoptosis by
      inducing intracellular Bcl-2.

PMID- 11249731
TI  - Monitoring cellular immune responses to cancer immunotherapy.
AB  - Many clinical trials are testing the feasibility of stimulating the immune system
      to treat cancer. Although the efficacy of this approach will ultimately be
      determined by clinically relevant endpoints, detection of the magnitude and
      activity of the immune response is an important intermediate point in the
      development of these strategies. Assays that predict clinically relevant
      endpoints are particularly desirable for helping to determine which strategies
      should ultimately be tested in larger randomized clinical trials. In this review,
      we will discuss these cellular immunological assays and the current status of
      their role in clinical trials of immunotherapy.

PMID- 11249732
TI  - Bi-specific antibody therapy for the treatment of cancer.
AB  - Bi-specific antibodies (BsAbs) combine immune cell activation with tumor cell
      recognition as a result of which tumor cells are killed by pre-defined effector
      cells. In this review a brief introduction to monoclonal antibodies will precede
      a more in-depth presentation of the current status of BsAb therapy for cancer.
      Target molecules and effector mechanisms aimed at tumor cells or aimed at tumor
      vasculature, and the application of recombinant DNA technology in the
      construction of antibodies, will be discussed. The lessons learned from the last
      decade will be discussed in consideration of the potential future development of
      BsAbs for cancer therapy.

PMID- 11249733
TI  - The anti-idiotype vaccines for immunotherapy.
AB  - Certain anti-idiotypic antibodies that bind to the antigen-combining sites of
      antibodies can effectively mimic the three-dimensional structures and functions
      of the external antigens and can be used as surrogate antigens for active
      specific immunotherapy. Extensive studies in animal models have demonstrated the
      efficacy of these vaccines for triggering the immune system to induce specific
      and protective immunity against bacterial, viral and parasitic infections as well
      as tumors. Several monoclonal anti-idiotype antibodies that mimic distinct human
      tumor-associated antigens have been developed and characterized. Encouraging
      results have been obtained in recent clinical trials using these anti-idiotype
      antibodies as vaccines. In this article, we will review the current literature
      and discuss the potential of this novel therapeutic approach for various human
      cancers.

PMID- 11249734
TI  - Immunotherapy of renal cell carcinoma by intratumoral administration of an IL-2
      cDNA/DMRIE/DOPE lipid complex.
AB  - Intratumoral administration of cytokine genes in order to achieve paracrine
      secretion of immunostimulatory cytokines and to create tumor vaccines in situ can
      avoid difficulties associated with the production of autologous and allogeneic
      vaccines, and toxicity related to systemic administration of cytokines. In this
      review, we summarize our experience with intratumoral administration of IL-2
      cDNA/DMRIE/DOPE lipid complex in patients with metastatic renal cell carcinoma.
      An objective response rate of 14% was achieved in a phase I/II clinical trial and
      was confirmed in the low-risk subgroup of a phase II study. The achieved
      objective clinical responses (PR/CR) were long lasting. Application of PCR and
      immunohistochemistry in post-treatment tumor biopsies detected the IL-2 plasmid
      in addition to increased IL-2 expression in tumor cells and CD8 infiltration.
      Clinical trials employing higher doses of the plasmid in renal cell carcinoma
      patients with limited disease are ongoing.

PMID- 11249735
TI  - Chemotherapy: friend or foe to cancer vaccines?
AB  - Cancer vaccines are on the threshold of taking their place alongside the more
      traditional cancer treatment modalities of surgery, radiation therapy and
      chemotherapy. The toxicology and immunopharmacology of therapeutic cancer
      vaccines, particularly those that secrete granulocyte macrophage colony
      stimulating factor (GM-CSF), are currently under active clinical investigation.
      Interestingly, drugs traditionally used for tumor cytoreduction can have both
      positive and negative effects on host immunity. Exploration of the potential
      pharmacodynamic interactions of antineoplastic drugs with GM-CSF-secreting
      vaccines has revealed that low doses of some chemotherapeutics can augment the
      antitumor immunity induced by GM-CSF-secreting vaccines. These interactions will
      require thorough preclinical evaluation to maximize the clinical impact of this
      type of therapeutic cancer vaccine.

PMID- 11249736
TI  - Technology evaluation: SAGE, Genzyme molecular oncology.
AB  - Genzyme Molecular Oncology (GMO) is using its SAGE (Serial Analysis of Gene
      Expression) combinatorial chemistry technology to screen compound libraries. SAGE
      is a high-throughput, high-efficiency method to simultaneously detect and measure
      the expression levels of genes expressed in a cell at a given time, including
      rare genes. SAGE can be used in a wide variety of applications to identify
      disease-related genes, to analyze the effect of drugs on tissues and to provide
      insights into disease pathways. It works by isolating short fragments of genetic
      information from the expressed genes that are present in the cell being studied.
      These short sequences, called SAGE tags, are linked together for efficient
      sequencing. The sequence data are then analyzed to identify each gene expressed
      in the cell and the levels at which each gene is expressed. This information
      forms a library that can be used to analyze the differences in gene expression
      between cells [293437]. By December 1999, GMO had identified a set of 40 genes
      from 3.5 million transcripts that were expressed at elevated levels in all cancer
      tissue but not seen in normal tissue. The company hope these may provide
      diagnostic markers or therapeutic targets. The studies also provided data
      furthering the understanding of the way cells use their genome [349968]. GMO has
      signed a collaborative agreement with the National Cancer Institute (NCI) to
      search for new drug candidates in the field of cancer chemotherapy. The
      collaboration combines GMO's SAGE technology with the NCI's extensive array of 60
      cell-based cancer screens. Under the agreement, the NCI will evaluate Genzyme's
      library consisting of one million compounds against selected cancer screens to
      identify compounds with anticancer properties [255082]. Xenometrix granted a
      license agreement for gene expression profiling to GMO in February 1999, giving
      company access to claims covered in issued US and European patents. The license
      is non-exclusive and covers the collection of gene expression profiles utilizing
      all methods including high-density microarrays [315329]. Ontogeny (now Curis Inc)
      and GMO have entered into a collaboration to study genes for the potential
      discovery of therapeutic products. GMO will use its SAGE technology to produce
      libraries of RNA supplied by Ontogeny. The libraries will be put through
      Ontogeny's screening program [279417]. Under an agreement made in August 1998,
      Bayer will use SAGE technology to identify genes and thus potential therapeutics
      [317452]. GMO and Hexagen signed an agreement in March 1998 on the use of SAGE
      technology in Hexagen's disease gene discovery programs. The first phase of the
      collaboration will focus on the use of SAGE in studies within Hexagen's type II
      diabetes gene discovery program. Hexagen has designed these studies to discover
      susceptibility genes for diabetes and to provide gene expression information for
      genes associated with type II diabetes [280012]. GMO signed a five-year agreement
      with Johns Hopkins University School of Medicine (JHU) in July 1997 for research
      leading to the identification of cancer-related genes. Under the terms of the
      agreement, JHU researchers will use the SAGE technology to identify and analyze
      gene expression in cancer. The power of SAGE in finding rare genes was confirmed
      in a study of gastrointestinal cancer by JHU researchers published in the May 27,
      1997 issue of Science. The study showed that of almost 50,000 genes expressed in
      normal gastrointestinal cells and gastrointestinal tumor cells, 86% of the genes
      were present at five or fewer copies per cell. Only 51% of those low-abundancy
      genes were recorded in the GenBank database of known genes in the human genome
      [257128].

PMID- 11249737
TI  - Technology evaluation: VEGF165 gene therapy, Valentis Inc.
AB  - Valentis Inc, formerly GeneMedicine, is developing a vascular endothelial growth
      factor (VEGF165) non-viral gene therapy using its proprietary PINC polymer for
      plasmid condensation. Two physician-initiated phase II angioplasty trials are
      ongoing, one for treating peripheral vascular disease and one for treating
      coronary artery disease [281714], [347153]. In February 2000, the trials were
      expected to be completed in the fourth quarter of 2000 [356225]; however, in
      October 2000, it was reported that the trial for peripheral vascular disease
      would be completed in the first quarter of 2001 [385232]. In March 2000, Valentis
      initiated a trial incorporating Valentis's DOTMA-based cationic lipid gene
      delivery system and the VEGF165 gene with Eurogene's local collar-reservoir
      delivery device. The trial is designed to demonstrate that the VEGF165 gene,
      delivered locally to the outside surface of a blood vessel, will transfect and
      express in the smooth muscle cells of the vessel wall [360683]. In March 1999,
      Valentis was awarded with a Phase II SBIR grant of $686,260. The aim of grant was
      to advance the development of non-viral gene therapies for ischemia.
      Specifically, Valentis intended to select an optimal promoter to be used with the
      VEGF expression plasmid. Valentis also intended to evaluate the gene therapy
      system in a rabbit ischemia model and complete the necessary preclinical studies
      for submission of an IND [318137].

PMID- 11249738
TI  - Web alert. Genomics and proteomics.

PMID- 11249739
TI  - The ATCG of drug discovery.
AB  - The publication of human and microbial genomic sequences has resulted in the
      availability of large amounts of data that are directly relevant to the discovery
      of novel and useful drug targets. The elucidation of the function of new genes is
      not a simple matter and human genetic studies have been among the most useful in
      identifying genes implicated in disease, although homologs, or orthologs, of
      human genes in mouse, worm, fly and yeast genomes have also been useful in
      deciphering gene function. The advent of genomics has led into the study of
      protein structure and function under the rubric of proteomics. Proteins function
      in a cell mostly by interacting with other proteins, and protein interaction maps
      of cellular circuits are now available. Screening strategies to address protein
      protein interactions are being developed, and many drug targets in the future are
      expected to be directed towards these interactions. In addition to using genetic
      and analytical approaches for finding new drug targets, chemical libraries can be
      used to inhibit the activity of new proteins, and thus reveal function. The
      combination of high-throughput screening with testing compounds for ADME
      (absorption, distribution, metabolism and excretion) and toxicity will help in
      the early clarification of clinical utility of both new drug targets, as well as
      drug candidates.

PMID- 11249740
TI  - Genomics and proteomics tools for the clinic.
AB  - The sequencing of the human genome was only made possible by the massively
      parallel use of automated high-throughput technologies. These technologies have
      required the development and interfacing of new hardware and software in a way
      which would have been hardly conceivable only ten years ago. As a consequence, an
      unbroken trend to more 'industrialized science' is apparent. The wealth of
      information generated by intensive sequencing efforts is now being further
      exploited by using complex tools to comprehensively analyze complex systems at
      the DNA, RNA and protein level. A landmark innovation was the introduction of the
      biochip principle, best exemplified with the development of the DNA chip, mainly
      used for RNA expression profiling. The chip principle, together with
      miniaturization, has now become the dominating theme for a number of new genomics
      and proteomics technologies, culminating in the lab-on-a-chip concept which, in
      the next five to ten years, could advance at a comparable rate to that of
      computers over the last 50 years. Some of the new technologies are already used
      for comprehensive analysis of clinical samples in an attempt to describe disease
      and disease risk at the molecular level. However, all of these technologies are
      far from routine in clinical use and it is also too early to decide whether
      molecular fingerprints or signature profiles will have the diagnostic and
      prognostic power currently predicted.

PMID- 11249742
TI  - Drug discovery, drug development and the emerging world of pharmacogenomics:
      prospecting for information in a data-rich landscape.
AB  - Drug development is a very expensive and inefficient process. Currently, it takes
      on average 15 years and costs approximately US $500 million to bring a new drug
      to market, with the pharmaceutical industry spending more than US $20 billion in
      identifying and developing drugs in 1998. Twenty-two percent of this total was
      spent on screening assays and toxicity testing. Yet the rapidly accelerating
      advances in high-throughput technologies, including screening and robotics,
      combinatorial chemistry, and genomics makes this an extremely data-rich
      environment. Add to that the new paradigms of pharmacogenomics and 'customized
      medicine', and the question is, are we helping or hurting our cause? Clearly,
      interpreting this flood of data and turning it into useful information is our
      next great hurdle. By extending the pharmacogenomic paradigm to the drug
      discovery process, this paper intends to put the scope of the problem into
      context.

PMID- 11249741
TI  - Proteomic strategies for biomarker identification: progress and challenges.
AB  - The simplest definition of a biomarker is a molecule that indicates an alteration
      in physiology from normal. A more practical definition of a biomarker would
      require clinical utility of this molecule. In this sense, the biomarker would
      specifically and sensitively reflect a disease state and could be used for
      diagnosis as well as for disease monitoring during and following therapy. The
      need for such biomarkers in all clinical fields is urgent, since the current
      arsenal of biomarkers is sadly deficient and, in most cases, non-specific. In
      this review, we discuss strategies that use a proteomics approach to identify
      novel biomarkers and give examples of recent studies employing these strategies.

PMID- 11249743
TI  - Bioinformatics, target discovery and the pharmaceutical/biotechnology industry.
AB  - With the first draft of the human genome now available a directed genome-wide
      mining strategy is being implemented by many pharmaceutical and biotechnology
      companies in order to identify novel members of the most therapeutically relevant
      target families. At the same time there is an increasing amount of annotation
      relevant to the human genome sequence entering into the public domain. The
      ability to identify protein families on a genome-wide scale can only be done at
      speed by using high-throughput computational approaches. This review describes
      many of the latest algorithmic developments in this field and shows how they can
      be best put to use for target identification and prioritization.

PMID- 11249744
TI  - Transdominant genetics, peptide inhibitors and drug targets.
AB  - The future of medical therapy is tied to the discovery of high-quality drug
      targets and drugs. Transdominant genetics provides a function-based route to
      peptide inhibitors that can be used as probes to identify protein targets or as
      reagents for drug development. Both forward-genetic and reverse-genetic
      applications have been implemented. The move is now underway to expand upon
      advances made in model systems and exploit screens of real therapeutic value.

PMID- 11249745
TI  - Gene targeted agents: new opportunities for rational drug development.
AB  - In addition to traditional drug development methods designed to modulate the
      activity of protein targets, knowledge of disease gene DNA sequences provides an
      opportunity for the highly rational design of therapeutic agents that act at the
      DNA level through sequence-specific interactions. Among the ligands capable of
      binding DNA in a precise, sequence-specific manner are oligonucleotides, peptide
      nucleic acids and polyamides. Various strategies employing these agents to either
      transiently or permanently alter gene expression have been investigated over the
      past decade. During the past two to three years, important steps have been taken
      to illustrate the therapeutic potential of these ligands. Triple-helix (triplex)
      forming oligonucleotides have been particularly effective DNA-targeting agents
      with a wide range of applications, including the positive and negative
      transcriptional regulation of target genes, as well as the controlled delivery of
      site-specific mutations. This review will focus upon recent advances involving
      the use of sequence-specific DNA-binding ligands to modify gene expression and/or
      structure, with particular emphasis on the use of triplex-forming
      oligonucleotides in these roles.

PMID- 11249746
TI  - Novel strategies for therapeutic design in molecular oncology using gene
      expression profiles.
AB  - The sequence of the human genome is estimated to be available by the end of the
      year 2000 [1]. Pursuant to deciphering the genomic code, and the identification
      of the estimated 40,000 to 100,000 human genes, anticipated technological
      advances will make possible examination of global gene expression profiles.
      Despite the current inaccessibility to the entire genome, many fruitful gene
      expression profiling studies have been performed using less than 10% of the
      predicted suite of genes in human or mouse genomes. Even within the confines of
      this limited set of genes, many insights and discoveries have resulted and their
      applications to cancer research are particularly profound. This review will focus
      on recent applications of gene expression profiling that have benefited three
      major areas of research in molecular oncology: (i) discovery--applications which
      have found novel genes, families of genes, or pathways involved in cell growth
      deregulation and tumor development; (ii) diagnosis--applications that have
      refined, and in some cases, defined, diagnostic methodology; and (iii)
      therapeutic design--applications which hold potential for chemotherapeutic drug
      discovery.

PMID- 11249747
TI  - Technology evaluation: gemtuzumab ozogamicin, Celltech Group.
AB  - Gemtuzumab ozogamicin (CMA-676) is a cytotoxic drug (calichaemicin) linked to a
      human monoclonal antibody that targets CD33, and which has been jointly developed
      and launched by Celltech Group and the Wyeth-Ayerst Research division of American
      Home Products as a treatment for acute myeloid leukemia (AML). Wyeth-Ayerst
      submitted an NDA to the US FDA in October 1999 for approval to treat AML patients
      who have relapsed after initial chemotherapy [346494]. In January 2000, the FDA
      assigned CMA-676 Priority Review status [351745], and in March 2000, the US FDA's
      Oncologic Drugs Advisory Committee voted that there was sufficient evidence of
      improved safety and acceptable efficacy to support accelerated approval for the
      treatment of AML in patients who have relapsed following initial chemotherapy
      [360113], [361883]. In May 2000, the FDA gave final approval for CMA-676 for the
      treatment of patients of 60 years and over in first relapse with CD33+ AML who
      are not considered candidates for cytotoxic chemotherapy [367212], [367215]. CMA
      676 was launched (as Mylotarg) in the US on 1 June 2000 by AHP. An EMAA is in
      preparation and is expected to be submitted by the end of 2000 [382163]. In
      September 2000, Merill Lynch predicted sales of 2.9 million Pounds in 2002,
      rising to 17.9 million Pounds in 2004 [383742], while in January 2000, Lehman
      Brothers predicted peak sales in excess of US$200 million [360128]. In December
      1999, Lehman Brothers predicted peak sales of US$150 million, with Celltech
      receiving royalties from AHP. Possible first-line therapy could follow depending
      on further studies, creating a potential market of US$300 million [352078].

PMID- 11249748
TI  - Technology evaluation: PRO-542, Progenics Pharmaceuticals inc.
AB  - Progenics's rCD4-IgG2 (PRO-542) is a recombinant fusion protein, which has been
      developed using the company's Universal Antiviral Binding (UnAB) technology, and
      is in phase I/II clinical trials for the treatment of human immunodeficiency
      virus type I (HIV-1) infection [273391]. At the beginning of 1997, Progenics
      received a Phase II Small Business Innovation Research Program (SBIR) grant from
      the National Institute of Allergy and Infectious diseases (NIAID) to fund the
      development of PRO-542 [236048]. A further grant of $2.7 million was awarded in
      August 1998 for the clinical evaluation of PRO-542 and other anti-HIV therapies
      [294200]. Progenics is collaborating with the Aaron Diamond AIDS Research Center
      (ADARC) in New York and the Center for Disease Control and Prevention in Atlanta
      [178410]. In February 2000, Progenics and Genzyme Transgenics Corp signed an
      agreement to continue the development of a transgenic source of PRO-542. Genzyme
      will develop transgenic goats that produce PRO-542 in their milk in exchange for
      undisclosed fees and milestone payments. Genzyme will supply PRO-542 to Progenics
      for clinical trials with a possibility for eventual commercial supply [357291].
      Following on from this, in October 2000, Progenics received an SBIR grant to fund
      a two-year project with Genzyme Transgenics into the development of cost
      effective methods for the manufacture of PRO-542, by optimization of the
      production of the drug in the milk of transgenic dairy animals [385982]. In
      August 2000, Punk, Ziegel & Company predicted that Progenics Pharmaceuticals will
      become sustainably profitable in 2003 following the launch of PRO-542 and GMK
      (Progenics Pharmaceuticals) in 2002 [390063].

PMID- 11249749
TI  - Technology evaluation: CN-706, Calydon Inc.
AB  - CN-706, an engineered adenovirus containing the prostate tissue-specific enhancer
      (PSE) gene is under development by Calydon as a potential treatment for prostate
      cancer. The company is collaborating with the Johns Hopkins Hospital, which has
      agreed to sponsor clinical trials [274956]. Phase I trials in patients with
      advanced and recurring prostate cancer began during 1998 at the Johns Hopkins
      Brady Urological Institute and the Oncology Center [283946], [296857], and the
      results of phase I/II trials were reported in 2000 [386879]. The US Patent Office
      issued three patents in October 1998 [301251] related to Calydon's technology for
      engineering viruses to replicate and kill prostate cancer cells [US-05648478],
      [US-05698443], [US-05783435]. In June 1999, Calydon was issued two further
      patents [US-05871726], [US-05830686], [327511].

PMID- 11249750
TI  - Web alert. Viruses as vectors for gene transfer.

PMID- 11249751
TI  - Lentiviral vectors: progress and potential.
AB  - Lentiviral vectors are continuing to generate great interest as gene vectors for
      possible gene therapy in vivo. Over the past year, considerable progress has been
      made in demonstrating gene delivery to a wide variety of tissues, taking
      advantage of their unique capability of integrating the desired gene into the
      chromosomes of the target cell. The basic science of lentivirus vector production
      has expanded and their relative ease of utility is reflected by the broadening
      range of laboratories reporting successful gene transfer using them. Important
      new findings on RNA processing within the cell have come from studies of vectors
      which have direct relevance to the molecular biology of HIV itself. Although none
      have been used in clinical trials in vivo, it can only be a matter of time before
      this occurs. This article reviews publications over the last 12 months,
      highlighting the major achievements in this field.

PMID- 11249752
TI  - Development of retroviral vectors for gene transfer to airway epithelia.
AB  - Retroviral vectors offer several potential advantages for attaining persistent
      expression of a therapeutic gene in airway epithelia for diseases such as cystic
      fibrosis. However, several problems have limited their application. Developments
      in vector production and the advent of lentiviral vectors have increased the
      investigation of recombinant retrovirus for gene transfer to airway epithelia. In
      addition, an improved understanding of some of the barriers limiting gene
      transfer has led to increased transduction efficiencies. The development of novel
      vector formulations and the use of new envelope pseudotypes are examples of
      recent findings that are leading to advances in this field.

PMID- 11249753
TI  - Alternative viral envelopes for oncoretroviruses to increase gene transfer into
      hematopoietic stem cells.
AB  - The hematopoietic stem cell is the target for gene therapy of human blood
      disease. Low retroviral receptors for the commonly used vectors and quiescence of
      hematopoietic stem cells are believed to be major obstacles to the success of
      gene therapy. The development of new stem cell assays has allowed better
      understanding of the biology and phenotype of hematopoietic stem cells, leading
      to selection of highly enriched populations of hematopoietic stem cells.
      Quantitation of retrovirus receptors on these enriched populations of
      hematopoietic stem cells has resulted in the identification of subpopulations of
      cells expressing high levels of retrovirus receptors. New promising retrovirus
      envelopes are being developed. In this review, we discuss those issues that may
      help to resolve the problem of low gene transfer efficiency into human
      hematopoietic stem cells.

PMID- 11249754
TI  - Adenovirus-mediated transfer of regulable gene expression.
AB  - The past several years have seen significant progress in the development of
      adenoviral vectors with markedly decreased pathological potential and greatly
      increased capacity for incorporation of foreign DNA. Paralleling these
      developments in gene transfer technology have been remarkable advances in both
      the design and optimization of gene regulatory systems. Ultimately, the goal of
      these gene regulatory systems is control of transgene expression in vivo by the
      administration of an exogenous compound. With the prospect of clinical human gene
      therapy on the horizon, the co-evolution of safe and efficient gene transfer
      strategies, with effective regulation of transgene expression, represents an
      essential step towards therapeutically viable gene transfer protocols. This
      review introduces recent advances in both adenoviral-based vectors and gene
      regulatory systems, and examines those studies in which adenoviral vectors and
      gene-regulatory systems have been combined in vivo.

PMID- 11249755
TI  - Biophysical targeting of adenovirus vectors for gene therapy.
AB  - Advances in understanding the interaction of animal viruses with their cognate
      receptors has led to improvements in the development of cell-specific, targeted
      viral vectors. Research strategies to generate safe, non-inflammatory viral
      vectors that are capable of delivering a therapeutic gene to a specific
      population of cells are currently underway in many laboratories. One approach in
      the utilization of this cell targeting activity is to ablate the natural
      interaction of the virus with its native receptor, although this is not an
      absolute requirement. The initial development of 'viral targeting strategies' was
      based on the view that by modifying the viral protein/receptor interaction, it
      would be possible to redirect virus vectors to new host cells. As the
      understanding of virus/cell interactions increased it was observed, however, that
      many viruses can use different entry mechanisms for cell attachment and
      penetration. Adenovirus vectors have been used extensively for the delivery of
      genes to cells. The entry mechanism for adenoviruses into cells has recently been
      studied and is relatively well understood, however, there are many aspects of
      cell receptor/virus interactions, which have still to be elucidated. The single
      high-affinity receptor on mammalian cells for adenovirus type 5 is recognized as
      the coxsackie and adenovirus receptor. However, in the absence of coxsackie and
      adenovirus receptor other receptors are used. A thorough understanding of the
      biology of adenoviruses is essential in the further development of their use as
      vectors for cell targeting. One strategy is to modify the viral capsid, either
      through coating the surface using bispecific antibodies, or by chemically
      crosslinking the targeting ligand onto the virion surface. Another approach is to
      genetically modify the virus by incorporating the targeting ligand into the viral
      'spike' (fiber) protein. This involves manipulating the adenovirus genome and
      generating a new targeting ligand on the surface of the fiber protein using
      recombinant DNA technology. The penton base protein has also received attention
      as a means of directing adenoviruses via insertion of novel targeting ligands.

PMID- 11249756
TI  - Herpesvirus vectors come of age.
AB  - Most human herpesviruses are ubiquitous and are closely associated with a number
      of severe acute infections and human tumors. Progress in herpesvirus genetics has
      made members of the herpesvirus family accessible, such that they have become
      more attractive as gene vectors to be used in the treatment of various diseases,
      including the prevention of herpesvirus-related afflictions. This review
      summarizes recent progress and provides a basis for development of new viral and
      therapeutic strategies.

PMID- 11249757
TI  - Gene therapeutic strategies for neurodegenerative diseases.
AB  - Gene transfer into the central nervous system by ex vivo or in vivo techniques is
      a rapidly emerging field in neuroscience. Potential applications of gene therapy
      for the nervous system include not only congenital single gene disorders, but
      also brain tumors and acquired chronic diseases. Considerable progress has been
      made in the understanding of neurodegenerative diseases such as Parkinson's and
      Alzheimer's disease. As a result, gene therapy for Parkinson's, and possibly
      Alzheimer's disease could be regarded as a realistic alternative to the limited
      treatment options currently available. In this review, we highlight the most
      important developments in gene transfer techniques as well as the newest insights
      in the mechanisms of some neurodegenerative disorders and put these into the
      perspective of gene therapeutic strategies for the central nervous system.

PMID- 11249758
TI  - Replicon-based vectors of positive strand RNA viruses.
AB  - Vectors based on self-replicating RNAs (replicons) of positive strand RNA viruses
      are becoming powerful tools for gene expression in mammalian cells and for the
      development of novel antiviral and anticancer vaccines. A relatively small genome
      size and simple procedure allow rapid generation of recombinants. Cytoplasmic RNA
      amplification eliminates nuclear involvement and leads to extremely high levels
      of gene expression, and continuous synthesis of double stranded RNA results in
      induction of enhanced immune responses, making these vectors unique among other
      gene expression systems. Both cytopathic replicon vectors allowing short-term
      transient expression, and non-cytopathic replicon vectors allowing long-term
      stable expression, are now available with the choice of vector depending on
      particular applications.

PMID- 11249759
TI  - SV40-based gene therapy vectors: turning an adversary into a friend.
AB  - For gene delivery to be of use, a situation suitable for delivery of genetic
      material, a specific genetic construct to be delivered and the appropriate means
      to deliver it are required. Simian virus-40 (SV40) gene therapy vectors for gene
      transfer may be an important advance in the latter category. While other vectors
      are variably limited for example by immunogenicity, difficulties in production,
      restricted specificity, low titers, poor transduction efficiency, etc.,
      recombinant viral vectors based on SV40 (rSV40) should not be similarly
      constrained. They are easily manipulated and produced at very high titer, stable,
      apparently lacking in immunogenicity, and capable of providing sustained high
      levels of transgene expression in almost any cell type, whether resting or
      dividing. The major limitation of SV40-derived vectors is packaging capacity,
      which restricts insert sizes. The rationale for developing SV40 as a gene therapy
      vector is reviewed, based on what is known of wild-type SV40. Studies with rSV40
      gene transfer have focused mostly on hematopoietic progenitor cells (CD34+) and
      their derivatives, and on gene delivery to the liver. In both settings, in vitro
      and in vivo, SV40 has been very effective. It is therefore a highly promising
      gene delivery vehicle that may complement other vectors that are currently in use
      or that are being developed.

PMID- 11249760
TI  - Technology evaluation: Abarelix, Praecis pharmaceuticals.
AB  - Abarelix (PPI-149) is a luteinizing hormone-releasing hormone (LHRH) receptor
      antagonist under development by Praecis, Amgen and Sanofi-Synthelabo for the
      potential treatment of prostate cancer, breast cancer and hormone-related
      disorders [285672,328910]. Abarelix has entered phase III clinical trials for
      hormonally responsive prostate cancer [311887], and a sustained-release
      formulation is in a phase I/II clinical trial for endometriosis [317822]. In June
      1997, Praecis entered into a collaboration with Sanofi-Synthelabo for the
      continued development and future marketing of Abarelix for the treatment of
      prostate cancer and other hormone-related disorders in Europe [248307]. In June
      1998, Roche gained marketing rights in the US and elsewhere, under a joint
      development agreement [289677], which was later terminated. In March 1999, Amgen
      gained rights to develop Abarelix in the US, Canada, Australia, Asia and other
      secondary markets [317822]. Sanofi-Synthelabo expects to launch the compound in
      Europe in 2001 [345341,346302]. In March 1999, Merrill Lynch predicted sales in
      2001 of US$75 million, with peak sales of up to US$400 million [336561]. In
      October 1999, Merrill Lynch predicted sales in 2003 of EUR 100 million [346209]
      and Lehman Brothers predicted sales of US$50 million in 2002 rising to a peak of
      US$150 million in 2010 [346267].

PMID- 11249761
TI  - Technology evaluation: Sch-58500, Canji.
AB  - Sch-58500 is a gene therapy utilizing the p53 gene and is under development by
      Canji and Schering-Plough for the potential treatment of various types of cancer.
      It is in phase II/III clinical trials in the US for stage III ovarian cancer
      [328228,328893], phase II clinical trials for hepatocellular and colorectal
      cancer metastatic to the liver [273331,324279], and phase I clinical trials for
      several other types of cancer [282801,284932,328228].

PMID- 11249762
TI  - Technology evaluation: edrecolomab, Centocor Inc.
AB  - Specific targeting of tumor cells may be achieved by using monoclonal antibodies
      to tumor antigens. Edrecolomab is a mouse-derived monoclonal IGg2A antibody
      directed against the human tumor-associated CO17-1A (or Ep-CAM) antigen, and is
      the first monoclonal antibody approved for cancer therapy. Encouraging results of
      several clinical trials were recently reported using edrecolomab for adjuvant
      therapy after surgery of Duke's C colorectal cancer. Side effects and toxicity
      profiles compare favorably to conventional regimens of radio- or chemotherapy.
      Future challenges lie in further improvement of these novel therapeutics,
      hopefully generating benefit for a larger number of cancer patients.

PMID- 11249764
TI  - Web alert. Gene therapy in cancer treatment.

PMID- 11249763
TI  - Technology evaluation: AAV factor IX gene therapy, Avigen Inc.
AB  - Avigen has developed a recombinant adeno-associated viral vector expressing human
      blood-coagulation Factor IX (F.IX) for the potential treatment of hemophilia B.
      In a phase I clinical trial being conducted at The Children's Hospital of
      Philadelphia and Stanford University Medical Center, the vector, AAV-CMV-hF.IX
      (Coagulin-B), was injected at a low dose into three patients with severe
      hemophilia B. No evidence of toxicity, germline transmission of vector sequences,
      or formation of inhibitory antibodies against F.IX was observed, and in two of
      the three patients there was an indication of a modest clinical response.

PMID- 11249765
TI  - Clinical applications of gene therapy.

PMID- 11249766
TI  - Gene therapy: recent progress in the clinical oncology arena.
AB  - Despite the rapid technological advances that continue to sustain the field of
      cancer gene therapy, few individual patients have benefited from the revolution
      so far. The plethora of clinical trials described confirms that each malignancy
      will have its own ideal strategy based on the associated molecular defects, and
      there has been rapid progress from this viewpoint. At the same time, there has
      been a renewed appreciation for the limitations to gene therapy, which include
      low efficiency of gene transfer, poor specificity of response and methods to
      accurately evaluate responses, and lack of truly tumor-specific targets at which
      to aim. As with all new therapies, we are climbing a steep learning curve in
      terms encountering treatment-related toxicities, as well as profound ethical and
      regulatory issues.

PMID- 11249767
TI  - Antivector and antitransgene host responses in gene therapy.
AB  - Current viral gene therapy vectors effectively transfer genes in vivo at the
      price of eliciting innate and acquired host responses against the vector and/or
      transgene. Antigens present in the viral vector and the expression of the
      transgene both cause cellular and humoral immune responses dependent on the viral
      vector, the route of administration, and the genotype and infection history of
      the host. In general, adenoviral vectors cause strong immune responses, which
      result in only transient expression of the therapeutic gene. Adeno-associated
      virus and retrovirus vectors elicit weaker immune responses and can therefore
      result in long-term gene transfer and expression. Methods to avoid host
      responses, including modification of viral vector and immunosuppression of the
      host, can increase the longevity and efficiency of gene transfer.

PMID- 11249768
TI  - Gene therapy for leukocyte adhesion deficiency.
AB  - Leukocyte adhesion deficiency (LAD) is an autosomal recessive immunodeficiency
      disease characterized by severe, recurrent bacterial infections. In patients with
      LAD, the leukocytes, particularly the neutrophils, fail to adhere to the
      endothelial cell wall and migrate to the site of infection. LAD results from
      heterogeneous molecular defects in the leukocyte integrin CD18, which prevent
      CD11/CD18 heterodimer formation and surface expression. To date, hematopoietic
      stem cell transplantation remains the only curative treatment for LAD, however,
      this approach is limited by transplant-related toxicities and graft-versus-host
      disease. During the course of the preceding decade we have conducted extensive
      experimental studies demonstrating that gene transfer of the CD18 subunit
      corrects the structural and functional defect in LAD leukocytes. These studies
      provided the support for the initiation of a clinical trial of retroviral
      mediated gene transfer of CD18 in two patients with the severe deficiency
      phenotype or LAD. This review will present an overview of LAD, preclinical CD18
      gene transfer studies and the initial results from the current clinical trial.

PMID- 11249769
TI  - Targeting therapeutic gene expression to human prostate cancers.
AB  - Most current therapies against human carcinoma of the prostate are palliative
      rather than curative. Thus, there is a pressing need for new therapies directed
      against this common tumor, based on knowledge of the basic biology of the
      prostate, rather than by extrapolation of treatments from other tumor types. This
      review presents the various levels of prostate targeting which could be and have
      been applied, at the attachment, expression and therapeutic gene levels to
      eliminate prostate carcinoma cells in extraprostatic sites. To achieve optimal
      and safe targeting, a combination approach will be necessary, as there are few
      genes whose expression can provide absolute prostate specificity.

PMID- 11249770
TI  - Progress towards hematopoietic stem cell gene therapy.
AB  - The introduction of recombinant genetic material into human cells for therapeutic
      purposes offers tremendous potential. However, almost from the beginning, the
      application of gene therapy has been characterized by the striking discrepancy
      between its promise and realization. Over the past 15 years, much has been
      learned about the various gene transfer systems and the requirements for
      efficient hematopoietic stem cell gene transfer. In the current review, we will
      summarize recent improvements in hematopoietic stem cell gene transfer, describe
      some of the promising results from recent clinical applications and the
      impediments that remain.

PMID- 11249772
TI  - Gene therapy for retinitis pigmentosa.
AB  - Retinitis pigmentosa (RP) is a group of retinal degenerative diseases in which
      there is a slow and progressive loss of photoreceptors. There is no cure for RP
      and photoreceptor loss leads ultimately to blindness. There has been tremendous
      progress in the last decade in delineating the molecular basis of RP.
      Simultaneously, gene transfer experiments have demonstrated that it is possible
      to deliver transgenes to the retina in vivo in a stable and efficient fashion
      with minimal toxicity. Proof-of-principle for gene therapy for RP has been
      established in a number of different animal models. While much more progress
      needs to be made before moving from the laboratory to the clinic, gene therapy
      now holds much promise for slowing or even preventing blindness due to RP.

PMID- 11249771
TI  - Micro-injection-mediated hematopoietic stem cell gene therapy.
AB  - Over the past decade, significant attention has been devoted to the development
      of viral vectors (i.e., retrovirus, lentivirus, adeno-associated virus) and
      conditions capable of transducing hematopoietic stem cells. After several years
      of disappointing results, recent reports in humans and other primates, most
      particularly the French report of successful treatment of X-linked severe
      combined immune deficiency (SCID) [1.], indicate that viral approaches will be
      successful in treating specific hematopoietic diseases. However, it is clear that
      alternate non-viral methods of gene delivery and genetic modification offer
      significant advantages, and may in fact be the only effective approach for
      treating certain blood diseases. In this review, we focus on glass needle
      mediated micro-injection as a method for the delivery of genetic material into
      blood stem cells, with an emphasis on molecules capable of either compensating
      gene deletions/mutations or directly repairing gene mutations.

PMID- 11249773
TI  - Gene therapy: a molecular approach to cancer treatment.
AB  - The current delineation of the molecular basis of cancer provides a strong
      rationale to consider gene therapy approaches for cancer as a complement to other
      cancer therapies. Phase III trials focused on adenoviral vector-mediated delivery
      of wild-type p53 to compliment p53 mutations were recently initiated for head and
      neck cancer and ovarian cancer. Clinical testing of the tumor inhibitory gene
      E1A, delivered by synthetic vectors is ongoing. Positive clinical data from these
      clinical studies will establish the use of gene therapy as a component of the
      multimodal treatment for certain cancers.

PMID- 11249774
TI  - Developments in suicide genes for preclinical and clinical applications.
AB  - The graduation of gene therapy from unfulfilled dreams to conventional therapy
      for genetic and acquired disorders will require a mastery of multiple disparate
      components including gene delivery vectors, regulated tissue-specific gene
      expression, control of immunity and manipulation of cell viability. Improvements
      in suicide genes have opened up a whole new treatment modality for treating
      hyperproliferative disorders and for designing animal models for disease. Along
      with herpes simplex virus-1 thymidine kinase, a host of additional suicide genes
      have been developed. A critical comparison of these will follow along with
      progress in utilizing these reagents for therapeutic benefits.

PMID- 11249775
TI  - The evolution of DNA vaccines.
AB  - Vaccination has eradicated smallpox and greatly decreased mortality and morbidity
      associated with a variety of viral and bacterial infectious diseases. However,
      conventional methodologies have failed to provide vaccines against many
      widespread deadly human diseases, among them HIV, malaria and cancer. Recombinant
      DNA vaccines have shown great promise in animal models in inducing protective
      immunity. In this review we will discuss their potential safe use in humans
      following recent advances in their use in animals, including non-human primates.

PMID- 11249776
TI  - Technology evaluation: gene therapy (IL-2), Valentis Inc.
AB  - Cationic lipid-DNA complexes are being evaluated for local or systemic
      therapeutic gene transfer. These positively charged liposomes fuse with
      negatively charged cell membranes and deliver the enclosed plasmid and its
      encoded gene to target tissues. This system has relevance for delivering genes to
      both normal and damaged or malignant tissues including phagocytes, tumor cells,
      endothelium and possibly parenchymal cells. Among the approaches being actively
      evaluated is the delivery of immunostimulatory cytokine genes (such as IL-2, IFN
      alpha or IL-12) into tumors. It is hypothesized that the local cytokine release
      will attract or induce antitumor immune responses. Valentis, (formerly
      GeneMedicine), has developed a plasmid encoding human IL-2 complexed with the
      liposomal preparation of DOTMA and cholesterol and has initiated phase I studies
      of intratumoral injection in head and neck cancer patients. Other routes of
      administration (intravenous and intratracheal), cytokines (IL-2) and proprietary
      liposomal-DNA complexes are being evaluated in preclinical models.

PMID- 11249777
TI  - Technology evaluation: Theratope, Biomira Inc.
AB  - Active specific immunotherapy, the use of 'vaccines' to stimulate therapeutic
      tumor antigen-specific immune responses, holds promise as a complementary
      approach to chemotherapy, radiation and surgery for the treatment of patients
      with cancers that have a high risk of relapse or progressive disease. Important
      components of an agent used for active immunotherapy are immunogens in the form
      of tumor-associated antigen(s) and an adjuvant or carrier molecule to promote
      presentation of the antigen to the immune effector cells. Possible antigens
      include tumor-expressed proteins or carbohydrate structures such as the
      glycoprotein mucin and its epitopes. The Theratope vaccine, consisting of a
      synthetic mimic of the mucin-associated glycan epitope STn conjugated to the
      carrier molecule keyhole limpet hemocyanin, has been developed for immunizing
      patients with mucin-expressing tumors. In murine and human studies, the vaccine
      has been shown to stimulate anti-STn antibodies and mucin-specific T-cell
      responses. The immune response is augmented by pretreatment with intravenous
      cyclophosphamide that serves to inhibit suppressor T-cells. Phase II studies
      suggested a survival benefit for breast cancer patients who received the
      Theratope vaccine after intravenous cyclophosphamide. A multinational phase III
      study testing the Theratope vaccine in patients with metastatic breast cancer who
      have had a clinical response or stability of disease is ongoing. Other
      malignancies for which the vaccine may be applicable include ovarian and
      gastrointestinal cancers.

PMID- 11249778
TI  - Technology evaluation: Valspodar, Novartis AG.
AB  - Valspodar (PSC-833) is a derivative of cyclosporin but devoid of the
      immunosuppressive and nephrotoxic properties seen in cyclosporin A. It exhibited
      high affinity binding to Mdr1 P-glycoprotein (P-gp) and demonstrated multidrug
      resistance-reversing activity superior to cyclosporin A and verapamil both in
      vitro and in vivo. Preclinical and phase I/II clinical data have indicated that
      plasma levels of PSC-833 with multidrug resistance-reversing activities are
      achievable. Potent inhibition of intestinal, hepatobiliary and blood-brain
      barrier P-gp function has been demonstrated. Since valspodar is also a substrate
      of cytochrome P450 3A (CYP3A), dual interactions of this compound with P-gp and
      CYP3A are the basis for the pharmacokinetic interactions seen in preclinical and
      clinical studies. A new formulation of the drug has recently been developed with
      better oral bioavailability (60%) and less interindividual variability. The
      toxicity profiles of valspodar are acceptable and dose-limited by transient and
      reversible cerebellar ataxia. It has shown multidrug resistance-modulating
      activities towards acute myeloid leukemia, multiple myeloma and ovarian cancer in
      phase I/II clinical trials. Phase III studies with respect to these three
      diseases are ongoing.

PMID- 11249779
TI  - Technology evaluation: GEM-231, Hybridon Inc.
AB  - Hybridon is conducting studies of the DNA methyltransferase gene and has
      identified specific sequences on mRNA as targets for chemically-modified
      antisense oligonucleotides. Hybridon has synthesized compounds that alter
      methylation of cultured human cancer cells and inhibit their ability to grow in
      cell culture and inhibit tumor formation in mice [191303]. The work is being
      carried out in collaboration with McGill University in Montreal and as part of a
      joint venture called MethylGene, set up by Hybridon and private investors. GEM
      231 (a mixed backbone oligonucleotide) is a strand of synthetic DNA, which has
      been modified with 2'-O-methyl ribose at both ends in order to resemble RNA. It
      has the ability to inhibit expression of the R1-alpha subunit of protein kinase
      A, a gene whose expression has been associated with many types of cancer
      [273331,275860].

PMID- 11249780
TI  - Monitoring of organotin compounds in seawater using semipermeable membrane
      devices (SPMDs)--tentative results.
AB  - The impact of anthropogenic pollutants on the marine ecosystem is related to the
      concentrations experienced by the biota in the seawater and the resulting
      concentration in the organism. Results from monitoring of pollutants in water
      samples provide snapshots that can be high or low depending on a wide range of
      variables. To provide more integrated information, semipermeable membrane
      devices, SPMDs, have been used to monitor different organic pollutants. In this
      survey, SPMDs were used to monitor organotin compounds in the marine environment.
      Time-integrated sampling using SPMDs and direct water sampling was carried out at
      six stations in the inner Oslofjord, Norway. The sample work-up procedure for
      both water and SPMDs was based on direct derivatisation using NaBEt4 and
      simultaneous extraction with an organic solvent. Analysis was performed using a
      gas chromatograph equipped with an atomic emission detector. The results show
      that SPMDs do accumulate organotin compounds from the water phase. Both tributyl-
      (TBT) and dibutyltin were detected in all of the analysed membranes while no
      monobutyltin was found. Levels found in SPMDs range from < 1 to 220 ng Sn SPMD(
      1). Water concentrations range from 0.4 to 10 ng Sn L(-1). An investigation of
      relative levels of TBT showed a similar concentration gradient in the inner
      Oslofjord using either direct water sampling or passive sampling by SPMDs. As the
      membranes are able to accumulate the organotins from the water it will be
      possible to locate lower concentrations than with direct analyses of water
      samples.

PMID- 11249781
TI  - Techniques and methods for the determination of haloacetic acids in potable
      water.
AB  - Haloethanoic (haloacetic) acids (HAAs) are formed as disinfection byproducts
      (DBPs) during the chlorination of natural water to make it fit for consumption.
      Sundry analytical techniques have been applied in order to determine the
      concentrations of the HAAs in potable water supplies: gas chromatography (GC-MS,
      GC-ECD); capillary electrophoresis (CE); liquid chromatography (LC), including
      ion chromatography (IC); and electrospray ionization mass spectrometry (ESI-MS).
      Detection limits required to analyze potable water samples can be regularly
      achieved only by GC-ECD and ESI-MS. Without improvements in preconcentration or
      detector sensitivity, CE and LC will not find application to potable water
      supplies. The predominant GC-ECD methods use either diazomethane or acidified
      methanol to esterify (methylate) the carboxylic acid moiety. For HAA5 analytes,
      regulated under the EPA's Stage 1 DBP Rule, diazomethane is satisfactory. For
      HAA9 data gathered under the Information Collection Rule, acidified methanol
      outperforms diazomethane, which suffers from photo-promoted side reactions,
      especially for the brominated trihaloacetic acids. Although ESI-MS can meet
      sensitivity and selectivity requirements, limited instrumentation availability
      means this technique will not be widely used for the time being. However, ESI-MS
      can provide valuable confirmatory information when coupled with GC-ECD in a
      research setting.

PMID- 11249782
TI  - Accuracy and traceability in environmental monitoring--pitfalls in methylmercury
      determinations as a case study.
AB  - The concepts of accuracy and traceability as applied to environmental analysis
      are still prone to misunderstandings. While accuracy refers to the closeness of
      analytical values to "true values" (trueness) and among various repetitions
      (precision), the term traceability implies a link of data obtained to established
      references through an unbroken chain of comparisons all with stated
      uncertainties. These misunderstandings, possibly occurring among the analytical
      community, may have consequences on environmental data interpretation. Recent
      discussions in the field of environmental speciation analysis illustrated that
      accuracy and traceability issues are still not firmly established within the
      environmental chemistry community. This paper discusses this issue, taking
      methylmercury as a case study.

PMID- 11249783
TI  - Determination of solvents permeating through chemical protective clothing with a
      microsensor array.
AB  - The performance of a novel prototype instrument in determining solvents and
      solvent mixtures permeating through samples of chemical protective clothing (CPC)
      materials was evaluated. The instrument contains a mini-preconcentrator and an
      array of three polymer-coated surface-acoustic-wave (SAW) microsensors whose
      collective response patterns are used to discriminate among multiple permeants.
      Permeation tests were performed with a 2.54 cm diameter test cell in an open-loop
      configuration on samples of common glove materials challenged with four
      individual solvents, three binary mixtures, and two ternary mixtures.
      Breakthrough times, defined as the times required for the permeation rate to
      reach a value of 1 microg cm(-2) min(-1), determined by the instrument were
      within 3 min of those determined in parallel by manual sampling and gas
      chromatographic analysis. Permeating solvents were recognized (identified) from
      their response patterns in 59 out of 64 measurements (92%) and their vapor
      concentrations were quantified to an accuracy of +/- 31% (typically +/- 10%).
      These results demonstrate the potential for such instrumentation to provide semi
      automated field or bench-top screening of CPC permeation resistance.

PMID- 11249784
TI  - Reliability of nitrogen dioxide passive diffusion tubes for ambient measurement:
      in situ properties of the triethanolamine absorbent.
AB  - Factors concerning NO2 uptake by the absorbent triethanolamine (TEA) in NO2
      diffusion tubes are examined. Although the nominal freezing point of TEA is 17.9
      21.2 degrees C, we show that, for a range of aqueous TEA solutions (0-20%, H2O),
      no freezing occurs even at -10 degrees C. Therefore NO2 collection efficiency is
      unlikely to be impaired by low temperature exposure. The recovery of TEA from the
      meshes of exposed samplers is determined as approximately 98%, even after 42
      days, showing that the stability in situ of TEA is unaffected by long-term
      exposure. A model of a diffusion tube sampling array for simultaneous exposures,
      with a 0.1 m sampler spacing, shows that NO2 uptake by individual samplers is not
      affected by the presence of neighbouring tubes in the array. This is confirmed by
      sampler precision at two Cambridge sites. Four sampler preparation methods are
      compared for differences in NO2 uptake of exposed samplers. All methods employ
      TEA as absorbent, transferred by either dipping meshes in a TEA-acetone solution
      or pipetting aliquots of a TEA-H2O solution onto the meshes. For samplers
      prepared by three of the methods, no difference in NO2 uptake is found, but for
      samplers prepared using a 50% v/v TEA-H2O solution, a mean reduction of 18% is
      found. Student's t-tests show that the difference is highly significant (P < or =
      0.001). Reasons for the difference are discussed.

PMID- 11249785
TI  - Performance evaluation of a sorbent tube sampling method using short path thermal
      desorption for volatile organic compounds.
AB  - Air sampling, using sorbents, thermal desorption and gas chromatography, is a
      versatile method for identifying and quantifying trace levels of volatile organic
      compounds (VOCs). Thermal desorption can provide high sensitivity, appropropriate
      choices of sorbents and method parameters can accommodate a wide range of
      compounds and high humidity, and automated short-path systems can minimize
      artifacts, losses and carry-over effects. This study evaluates the performance of
      a short-path thermal desorption method for 77 VOCs using laboratory and field
      tests and a dual sorbent system (Tenax GR, Carbosieve SIII). Laboratory tests
      showed that the method requirements for ambient air sampling were easily achieved
      for most compounds, e.g., using the average and standard deviation across target
      compounds, blank emissions were < or = 0.3 ng per sorbent tube for all target
      compounds except benzene, toluene and phenol; the method detection limit was 0.05
      +/- 0.08 ppb, reproducibility was 12 +/- 6%, linearity, as the relative standard
      deviation of relative response factors, was 16 +/- 9%, desorption efficiency was
      99 +/- 28%, samples stored for 1-6 weeks had recoveries of 87 +/- 9%, and high
      humidity samples had recoveries of 102 +/- 12%. Due to sorbent, column and
      detector characteristics, performance was somewhat poorer for phenol groups,
      ketones, and nitrogen containing compounds. The laboratory results were confirmed
      in an analysis of replicate samples collected in two field studies that sampled
      ambient air along roadways and indoor air in a large office building. Replicates
      collected under field conditions demonstrated good agreement except for very low
      concentrations or large (> 41 volume) samples of high humidity air. Overall, the
      method provides excellent performance and satisfactory throughput for many
      applications.

PMID- 11249786
TI  - Sampling techniques for the assessment of anthropogenic vapour and particulate
      mercury in the Brazilian Amazon atmosphere.
AB  - A system, based on annular gold-coated denuders, was optimized and used in the
      atmospheric sampling of mercury in urban and rural sites of the Alta Floresta, a
      region in the Brazilian Amazon. Results showed that vapour phase mercury (Hgv) is
      dominant in samples collected in both sites. However, particulate mercury (Hg)
      may sometimes be significant at the urban site, with values representing up to
      77% of the total Hg collected during sampling, but may also be insignificant at
      the same site, depending on the gold commercialization activity and, probably, on
      the meteorological conditions during the sampling period. The presence of mercury
      in both the vapour and particulate phases in the atmosphere of the urban site can
      explain the high mercury concentrations found in urban dust reported for some
      cities in the Amazon, and also the relatively high Hg concentrations found in
      soils adjacent to the urban centre of Alta Floresta. It appears that the urban
      dust of "garimpo" areas in the Amazon can act as an efficient adsorber of Hgv
      emitted by gold dealer operations during the purification process. Mercury
      emissions from gold dealer shops in the Amazon have been considered as a human
      health risk through the inhalation of Hg vapour. However, although true for
      indoor sites, the significant contribution of particulate phase Hg shown in this
      study in outdoor urban sites calls for a re-evaluation of the risk assessment
      estimates performed up to now in urban centres in the Amazon.

PMID- 11249787
TI  - Comparison of three sampling and analytical methods for the determination of
      airborne hexavalent chromium.
AB  - A field study was conducted with the goal of comparing the performance of three
      recently developed or modified sampling and analytical methods for the
      determination of airborne hexavalent chromium (Cr(VI)). The study was carried out
      in a hard chrome electroplating facility and in a jet engine manufacturing
      facility where airborne Cr(VI) was expected to be present. The analytical methods
      evaluated included two laboratory-based procedures (OSHA Method ID-215 and NIOSH
      Method 7605) and a field-portable method (NIOSH Method 7703). These three methods
      employ an identical sampling methodology: collection of Cr(VI)-containing aerosol
      on a polyvinyl chloride (PVC) filter housed in a sampling cassette, which is
      connected to a personal sampling pump calibrated at an appropriate flow rate. The
      basis of the analytical methods for all three methods involves extraction of the
      PVC filter in alkaline buffer solution, chemical isolation of the Cr(VI) ion,
      complexation of the Cr(VI) ion with 1,5-diphenylcarbazide, and spectrometric
      measurement of the violet chromium diphenylcarbazone complex at 540 nm. However,
      there are notable specific differences within the sample preparation procedures
      used in three methods. To assess the comparability of the three measurement
      protocols, a total of 20 side-by-side air samples were collected, equally divided
      between a chromic acid electroplating operation and a spray paint operation where
      water soluble forms of Cr(VI) were used. A range of Cr(VI) concentrations from
      0.6 to 960 microg m(-3), with Cr(VI) mass loadings ranging from 0.4 to 32 microg,
      was measured at the two operations. The equivalence of the means of the log
      transformed Cr(VI) concentrations obtained from the different analytical methods
      was compared. Based on analysis of variance (ANOVA) results, no statistically
      significant differences were observed between mean values measured using each of
      the three methods. Small but statistically significant differences were observed
      between results obtained from performance evaluation samples for the NIOSH field
      method and the OSHA laboratory method.

PMID- 11249788
TI  - Influences of metal cations on the determination of the alpha-oxocarboxylates as
      the methyl esters of the O-(2,3,4,5,6-pentafluorobenzyl)oximes by gas
      chromatography: the importance of accounting for matrix effects.
AB  - The alpha-oxocarboxylates alpha-ketocarboxylates) and the corresponding alpha
      oxoacids (alpha-ketoacids) have been reported as disinfection byproducts of
      ozonation of potable water supplies. In this analytical method, the oxo moiety is
      derivatized with O-(2,3,4,5,6-pentafluorobenzyl)oxylamine (PFBOA) to form an
      oxime which is then extracted into tert-butyl methyl ether. The carboxylic acid
      moiety is esterified (methylated) with diazomethane. In this study, five analytes
      were investigated: oxoethanoate (glyoxylate), 2-oxopropanoate (pyruvate), 2
      oxobutanoate (2-ketobutyrate), 2-oxopentanoate (2-ketovalerate), and
      oxopropanedioate (ketomalonate, mesoxalate). The influence of Lewis acid metal
      cations in the water matrix was evaluated for the gas chromatographic method
      commonly used for the quantitation of these analytes at concentrations < or = 150
      ng mL(-1). Tested metals included Ca(II), Mg(II), Fe(III), Cu(II) and Zn(II). At
      typical concentrations, calcium, in particular, can have profound impact,
      especially on oxoethanoate quantitation. Oxopropanoate experiences an increase in
      recovery in the presence of metal cations. 2-Oxobutanoate and 2-oxopentanoate are
      the most resistant to these effects, but 2-oxopentanoate shows increased
      recoveries at higher concentrations when assayed in the presence of calcium ion.
      Oxopropanedioate generally shows poorer precision and recovery when determined in
      solutions containing metal ions. This investigation demonstrates the significance
      of metal effects in the quantitative determination of these analytes and further
      emphasizes the importance of thorough matrix characterization and careful
      recovery studies with fortified (spiked) samples and blanks.

PMID- 11249789
TI  - Determination of hydrogen peroxide in workplace air: interferences and method
      validation.
AB  - A dynamic system for the generation of stable hydrogen peroxide test atmospheres
      was applied to the evaluation of samplers used for the determination of hydrogen
      peroxide in workplace air. The system is able to generate gas mixtures of between
      0.1 and 10 ppm at different combinations of relative humidity (20-80%) and
      temperature (10-30 degrees C). Gaseous hydrogen peroxide is sampled on glass
      filters impregnated with Ti(IV) chloride and sulfuric acid and analyzed by UV
      spectroscopy. An interference was observed due to the acid catalyzed
      decomposition of peroxyacetic acid to hydrogen peroxide. This was significantly
      reduced by applying high sample flow rates and by lowering the concentration of
      sulfuric acid. The performance of the sampler and sources of uncertainties were
      tested according to the European Standard EN 1076.

PMID- 11249790
TI  - Air pollution exposure monitoring and estimation VII. Estimation of population
      exposure in a central European airshed.
AB  - In order to clarify the local variation in exposure and source-receptor
      relationships, a dispersion model for estimating air pollution concentrations was
      developed for a polluted area in the Czech Republic. Three models characterized
      by different spatial resolution were integrated into one modelling tool. A
      regional-scale dispersion model accounted for pollution contribution from sources
      outside the modelling area. Local- and urban-scale dispersion models were used to
      calculate local concentration distributions. Calculated concentration
      distributions were evaluated. Deviations between observed and calculated
      concentrations were not correlated in space, except in episodes, and
      concentrations measured at spatially representative stations were assimilated
      into the model results using statistical interpolation (simple kriging). The
      results indicated that centralized heating plants and local home heating were the
      most important sources for sulfur dioxide (SO2) pollution. Both high and low
      level sources may contribute to the accumulation of pollution concentrations in
      episodes. The measured concentrations were important for the description of
      distributions in episodes characterized by complex wind and dispersion
      conditions. The applicability of source oriented model calculations to correctly
      represent measured concentrations in the pollution episodes was limited due to
      the fact that meteorological conditions representative of high concentration
      episodes were characterized by very low wind speed and variable wind directions.
      About 8,000 individuals were given an exposure estimate representing contribution
      from local emissions, based on the estimated hourly outdoor exposure to SO2 at
      their home/work addresses in the 3 month study period in the autumn of 1991. The
      results showed that, for 5% of participants, the maximum hourly contribution of
      local emissions was over 380 microg m(-3). For the 3 month average, both large
      scale and local-scale pollution contribute significantly. For primary compounds,
      such as SO2, steep gradients are observed in the vicinity of strong local
      sources. These gradients are important for exposure characteristics and health
      effect quantification, and often will not be captured by an existing monitoring
      network. The calculations can be extended to other periods or to different
      compounds.

PMID- 11249791
TI  - Reference values for chromium, nickel and vanadium in urine of youngsters from
      the urban area of Rome.
AB  - In the assessment of human health risk, the obtainment of reference values in
      biological tissues and/or fluids is crucial to estimate the type and magnitude of
      occupational and environmental exposure. In this context, urine is the major
      excretion route for many noxious substances that have entered the organism and
      can be viewed as one of the most useful materials for biomonitoring campaigns. In
      this study, reference concentration ranges for Cr, Ni and V in urine were
      achieved in a sub-population of 131 youngsters, aged 6-10, attending primary
      schools in the urban area of Rome. Subjects under drug therapy or affected by any
      pathological diseases were not included in this investigation. Strict precautions
      against contamination or loss of the analytes of interest were adopted for all
      steps. Determinations were performed by means of high resolution inductively
      coupled plasma mass spectrometry. In general, the natural log-transformed
      concentration data for the three elements investigated conformed to a
      satisfactorily normal distribution. The estimated reference ranges were as
      follows (microg g(-1) creatinine): Cr, 0.07-0.76; Ni, 0.20-1.23; V, 0.02-0.22.
      The sex of the youngsters was tentatively treated as a statistical explanatory
      variable using the Fischer F-test on variance.

PMID- 11249792
TI  - Speciation of gold(III)-L-histidine complex: a multi-instrumental approach.
AB  - The formation and structure of gold (III)-L-histidine complex was investigated
      with the use of carbon (13C) and proton (1H) nuclear magnetic resonance (NMR),
      infrared (IR) spectroscopy, capillary electrophoresis (CE), capillary
      electrophoresis-inductively coupled plasma-mass spectroscopy (CE-ICP-MS), X-ray
      fluorescence spectroscopy (XRF), matrix-assisted laser desorption/ionization
      (MALDI), and laser desorption mass spectroscopy (LDMS). It was found that two L
      histidine molecules and one gold ion slowly form a complex in acidic solution.
      Each L-histidine molecule provided two nitrogen ligands; one was the alpha-amino
      group and the other from the imidazole ring. The Au(III)-bis-L-histidine complex
      precipitates after deprotonation of the free carboxylic group, resulting in an
      increase in the solution acidity. Determination of the exact sequence of events
      and the identity of the complex was a comprehensive instrumental analysis problem
      involving the above techniques.

PMID- 11249793
TI  - Chemical availability of mercury in stream sediments from the Almaden area,
      Spain.
AB  - The chemical speciation, fractionation and availability of mercury in sediments
      from a cinnabar mining area (Almaden, Spain) was studied with different
      extraction and analytical procedures, in order to determine the degree to which
      the ecosystem is harmed by this pollutant. Three total extraction procedures, a
      sequential extraction and the speciation of organo-mercury compounds were
      performed in nine sediment samples. In the study area, although concentrations of
      mercury can be extremely high (up to 1,000 mg kg(-1)), no organomercury compounds
      were detected (< 2 microg kg(-1) and the availability of this element seems
      restricted. One of the methods for total extraction presented considerably lower
      recovery in Almaden's sediments, yet the results were controlled with certified
      reference materials. This disagreement was attributed to the fact that the
      mercury is in a refractory form. Sequential extraction was able to show that most
      of the mercury is associated with sulfides (probably as metacinnabar) or in the
      residual refractory phase (probably as red cinnabar).

PMID- 11249794
TI  - Simple and sensitive spectrophotometric determination of ziram, zineb and ferbam
      in commercial samples and foodstuffs using phenylfluorone.
AB  - A procedure has been developed for the determination of ziram, zineb and ferbam
      dithiocarbamate pesticides by converting ziram and zineb into a zinc
      phenylfluorone complex and ferbam into an iron phenylfluorone complex, which are
      then dissolved in water in the presence of cetylpyridinium bromide and pyridine
      as a surfactant. The method is sensitive, highly selective and can be used for
      the determination of ziram, zineb and ferbam in commercial samples and in
      foodstuffs.

PMID- 11249795
TI  - Isolation of coliphages specific to enterotoxigenic E. coli (ETEC).
AB  - Bacteriophages specific to Enterotoxigenic E. coli (ETEC) are reported for the
      first time. Out of 15 isolated phages only 10 were specific to strains of ETEC.
      All ten phages of dsDNA could be grouped into three different genotypes based on
      their RAPD patterns observed and it is likellly that they belong to only 3
      different strains. The three phages yielded clear plaques on 10 strains of ETEC
      within 4-6 h at 37 degrees C.

PMID- 11249796
TI  - Mercury, cadmium, lead, and selenium in fish from a Norwegian fjord and off the
      coast, the importance of sampling locality.
AB  - Hepatic levels of mercury, cadmium, lead, and selenium and levels of mercury and
      selenium in muscle tissue were analysed in tusk from the Nordfjord in Norway.
      With the exception of selenium in the muscle tissue, the metal levels were
      significantly higher in the fjord fish than in fish caught off the coast. No
      local source is known to explain the difference in levels, and this indicates
      that the fjord efficiently accumulates atmospheric contaminants. The present
      results demonstrate the importance of sampling area when determining levels of
      metals in marine organisms far from point sources. The liver was increasingly
      used as a storage compartment for mercury and selenium with increasing exposure.

PMID- 11249797
TI  - Fluorescent screening of phytoplankton and organic compounds in sea water.
AB  - The flow-through spectrofluorometers, FLUO-IMAGER, were developed to measure the
      abundance of phytoplankton, including the analysis of pigment composition and
      concentration of organic pollution and dissolved organic matter (DOM), in
      continuous mode. The measurements can be carried out without the time-consuming
      pretreatment of water samples. The analytical concept uses the technique of
      spectral fluorescent signatures (SFS), based on the systematized spectral library
      comprising the SFS of major phytoplankton species and chemical pollution. The SFS
      technique has been applied for several years in qualitative and quantitative
      screening of organic compounds and phytoplankton in the Baltic, North and
      Norwegian Seas. The results of the analysis of phytoplankton pigments, the
      dynamic processes of bloom development, DOM and oil pollution are presented.

PMID- 11249798
TI  - Expedited registration review in the USA: the EPA's reduced risk program.

PMID- 11249799
TI  - Choline, myo-inositol and mood in bipolar disorder: a proton magnetic resonance
      spectroscopic imaging study of the anterior cingulate cortex.
AB  - OBJECTIVES: Alterations in choline and myo-inositol metabolism have been noted in
      bipolar disorder, and the therapeutic efficacy of lithium in mania may be related
      to these effects. We wished to determine the relationship between anterior
      cingulate cortex choline and myo-inositol levels, assessed using proton magnetic
      resonance spectroscopic imaging (MRSI), and mood state in subjects with bipolar
      disorder. METHODS: Serial assessments of anterior cingulate cortex choline and
      myo-inositol metabolism were performed in nine subjects with bipolar disorder,
      taking either lithium or valproate, and 14 controls. Each bipolar subject was
      examined between one and four times (3.1 +/- 1.3). On the occasion of each
      examination, standardized ratings of both depression and mania were recorded.
      RESULTS: In the left cingulate cortex, the bipolar subjects' depression ratings
      correlated positively with MRSI measures of Cho/Cr-PCr. In the right cingulate
      cortex, the Cho/Cr-PCr ratio was significantly higher in subjects with bipolar
      disorder compared with control subjects. In addition, bipolar subjects not taking
      antidepressants had a significantly higher right cingulate cortex Cho/Cr-PCr
      ratio compared with patients taking antidepressants or controls. No clinical or
      drug-related changes were observed for the Ino/Cr-PCr ratio. CONCLUSIONS: The
      results of this study suggest that bipolar disorder is associated with
      alterations in the metabolism of cytosolic, choline-containing compounds in the
      anterior cingulate cortex. As this resonance arises primarily from phosphocholine
      and glycerophosphocholine, both of which are metabolites of phosphatidylcholine,
      these results are consistent with impaired intraneuronal signaling mechanisms.

PMID- 11249800
TI  - Lithium regulates PKC-mediated intracellular cross-talk and gene expression in
      the CNS in vivo.
AB  - It has become increasingly appreciated that the long-term treatment of complex
      neuropsychiatric disorders like bipolar disorder (BD) involves the strategic
      regulation of signaling pathways and gene expression in critical neuronal
      circuits. Accumulating evidence from our laboratories and others has identified
      the family of protein kinase C (PKC) isozymes as a shared target in the brain for
      the long-term action of both lithium and valproate (VPA) in the treatment of BD.
      In rats chronically treated with lithium at therapeutic levels, there is a
      reduction in the levels of frontal cortical and hippocampal membrane-associated
      PKC alpha and PKC epsilon. Using in vivO microdialysis, we have investigated the
      effects of chronic lithium on the intracellular cross-talk between PKC and the
      cyclic AMP (cAMP) generating system in vivo. We have found that activation of PKC
      produces an increase in dialysate cAMP levels in both prefrontal cortex and
      hippocampus, effects which are attenuated by chronic lithium administration.
      Lithium also regulates the activity of another major signaling pathway the c-Jun
      N-terminal kinase pathway--in a PKC-dependent manner. Both Li and VPA, at
      therapeutically relevant concentrations, increase the DNA binding of activator
      protein 1 (AP-1) family of transcription factors in cultured cells in vitro, and
      in rat brain ex vivo. Furthermore, both agents increase the expression of an AP-1
      driven reporter gene, as well as the expression of several endogenous genes known
      to be regulated by AP-1. Together, these results suggest that the PKC signaling
      pathway and PKC-mediated gene expression may be important mediators of lithium's
      long-term therapeutic effects in a disorder as complex as BD.

PMID- 11249801
TI  - fMRI during affect discrimination in bipolar affective disorder.
AB  - OBJECTIVE: It has been hypothesized that disturbances in affect may represent
      distinct etiologic factors for bipolar affective disorder. The neural mechanisms
      mediating affective processes and their relationship to brain development and the
      pathophysiology of bipolar affective disorder remain to be clarified. Recent
      advances in neuroimaging techniques have made possible the non-invasive
      examination of specific brain regions during cortical challenge paradigms. This
      study reports findings based on fMRI data acquired during fearful and happy
      affect recognition paradigms in patients with bipolar affective disorder and in
      healthy adult subjects. METHODS: Prior to the scan, subjects were instructed to
      view the stimuli and to identify the type of facial expression presented. Echo
      planar scanning was performed on a 1.5 Tesla scanner which had been retrofitted
      with a whole body echo planar coil, using a head coil. RESULTS: The data indicate
      that in adult subjects with bipolar affective disorder, there is a reduction in
      dorsolateral prefrontal cortex activation and an increase in amygdalar activation
      in response to fearful facial affect. In a healthy comparison group, signal
      intensity changes were not found in these regions. In addition, although the
      patients with bipolar affective disorder completed the task demands, they
      demonstrated an impaired ability to correctly identify fearful facial affect but
      not the happy facial affect displayed. CONCLUSION: These findings are consistent
      with the hypothesis that in some patients with bipolar affective disorder, there
      may be a reduction of frontal cortical function which may be associated with
      affective as well as attentional processing deficits.

PMID- 11249802
TI  - Gabapentin in bipolar disorder: a placebo-controlled trial of adjunctive therapy.
      Gabapentin Bipolar Disorder Study Group.
AB  - OBJECTIVES: [corrected] To assess efficacy and safety of gabapentin in the
      treatment of bipolar disorder. METHODS: This was a double-blind, placebo
      controlled trial of adjunctive gabapentin (dosed flexibly between 900 and 3,600
      mg/day). Patients with a lifetime diagnosis of bipolar disorder (type I), and who
      were currently suffering from symptoms of either mania, hypomania or a mixed
      state despite ongoing therapy with lithium, valproate, or lithium and valproate
      in combination were eligible for inclusion. The primary efficacy measures were
      the baseline to endpoint change in total score on the Young Mania Rating Scale
      (YMRS) and the Hamilton Depression Rating Scale (HAM-D). RESULTS: Both treatment
      groups had a decrease in total YMRS from baseline to endpoint, but this decrease
      was significantly greater in the placebo group (-9) than the gabapentin group (
      6) (p < 0.05). No difference between treatments was found for the total score on
      the HAM-D. Secondary efficacy measures were not different between treatment
      groups. More patients in the placebo group had changes made to their ongoing
      lithium therapy (n = 12) compared to the gabapentin group (n = 4). When these
      patients are removed from the efficacy analysis, the YMRS treatment difference
      still favors placebo, but is no longer statistically significant. Based on
      gabapentin plasma levels at termination, some patients did not take the study
      drug as prescribed. CONCLUSIONS: The findings of this study did not demonstrate
      that gabapentin is an effective adjunctive treatment when administered to
      outpatients with bipolar disorder.

PMID- 11249803
TI  - The treatment of bipolar depression.
AB  - OBJECTIVES: The treatment of the depressed phase of bipolar disorder is
      understudied and remains a common clinical dilemma for clinicians. Compared to
      the manic phases, episodes of bipolar depression are more frequent and of longer
      duration, yet the literature on this problem is minimal. The few methodologically
      sound studies find that treatment effective for unipolar depression are also
      efficacious for bipolar depression. However, standard antidepressant agents may
      cause acute mania or a long-term worsening of bipolar illness. This paper reviews
      the available literature on the treatment of bipolar depression and offers
      recommendations for clinical management. METHODS: A literature search was
      conducted using keywords 'bipolar disorder', 'depression', 'drug therapy',
      'antidepressants', 'lithium', and 'anticonvulsants'. RESULTS: If effectively
      treated by lithium, patients are spared the risk of antidepressant-induced mania.
      If lithium is not sufficient treatment for acute depression, the combination of
      lithium and a standard antidepressant appears to reduce the risk of affective
      switch, as well as the induction of a long-term rapid-cycling course.
      Additionally, tapering antidepressant medication after periods of sustained
      remission can be beneficial in limiting the risk of affective switch and
      acceleration of the cycle rate. CONCLUSIONS: Doctors must be cautious in
      prescribing antidepressants for bipolar depression. Use of antidepressants alone
      should be avoided.

PMID- 11249804
TI  - Onset of action of antipsychotics in the treatment of mania.
AB  - INTRODUCTION: An important consideration in treating acute mania is the
      promptness with which a chosen therapy can bring symptom amelioration. This
      article reviews the available published data from controlled, blinded studies
      regarding the latency of responses to antipsychotics in patients with acute
      mania. METHODS: Articles for this review were obtained from a search of the
      Medline database (1966- 1999), using the following keywords and phrases:
      antipsychotic, atypical, bipolar disorder, mania, neuroleptic, typical. The
      bibliographic sections of articles gleaned from this search were used to direct
      further inquiries. RESULTS: Although information regarding the onset of action of
      antipsychotics is limited, we discovered data for four typical and three atypical
      antipsychotics. Drugs with the fastest onsets include haloperidol, risperidone,
      and olanzapine, with onsets appearing in 2 6 days. Chlorpromazine and thiothixene
      were at the slowest end of the continuum, with onsets of 2 weeks or longer. Data
      regarding pimozide are mixed, with some studies showing an onset equivalent to
      that of the 'fast' compounds and others showing one similar to that of the 'slow'
      compounds. CONCLUSIONS: Choice of therapy should consider not only efficacy and
      safety, but also onset speed. Atypical antipsychotics appear to offer safer,
      faster, and more effective therapies.

PMID- 11249805
TI  - Impact of substance abuse on the course and treatment of bipolar disorder.
AB  - OBJECTIVES: The objectives of this article are to review the prevalence, natural
      history, pathophysiology, and treatment of comorbid bipolar disorder with
      alcoholism and other psychoactive substance use disorders (PSUDs). METHODS: All
      identified bibliographies through a literature search of all Medline files and
      bibliographies of selected articles focusing on the prevalence, natural history,
      course, prognosis, inter-relationship, and treatment of bipolar disorder with
      comorbid alcoholism and other PSUDs were reviewed. RESULTS AND CONCLUSIONS:
      Comorbidity of bipolar disorder and alcoholism and other PSUDs is highly
      prevalent. The presence of this so called 'dual diagnoses' creates a serious
      challenge in terms of establishing an accurate diagnosis and providing
      appropriate treatment interventions. The inter-relationship between these
      disorders appears to be mutually detrimental. The course, manifestation, and
      treatment of each condition are significantly compounded by the presence of the
      other condition. Substance abuse and alcoholism appear to significantly
      complicate the course and prognosis of bipolar disorder resulting in increased
      suffering, disability, and costs. On the other hand, bipolar disorder may be a
      risk factor for developing PSUDs. Although, there are a number of hypotheses
      explaining the pathophysiological mechanism involved in such comorbidities, our
      understanding of the exact nature of such neurobiological mechanisms is still
      limited. While the antikindling agents and targeted psychotherapeutic techniques
      may be useful intervention strategies, there is still a significant lack of
      empirically based treatment options for these patients.

PMID- 11249806
TI  - Bipolar disorder during adolescence and young adulthood in a community sample.
AB  - OBJECTIVES: To compare the incidence and prevalence of bipolar disorder (BD)
      between adolescence and young adulthood; to explore the stability and
      consequences of adolescent BD in young adulthood; to determine the rate of
      switching from major depressive disorder (MDD) to BD; and to evaluate the
      significance of subsyndromal BD (SUB). METHODS: A large, randomly selected
      community sample (n = 1,507) received diagnostic assessments twice during
      adolescence, and a stratified subset (n = 893) was assessed again at 24 years of
      age. In addition, direct interviews were conducted with all available first
      degree relatives. Five mutually exclusive groups, based on diagnoses in
      adolescence, were compared: BD (n = 17), SUB (n = 48), MDD (n = 275), disruptive
      behavior disorder (n = 49), and no-disorder (ND) controls (n = 307). RESULTS:
      Lifetime prevalence of BD was approximately 1% during adolescence and 2%, during
      young adulthood. Lifetime prevalence for SUB was approximately 5%. Less than 1%,
      of adolescents with MDD 'switched' to BD by age 24. Adolescents with BD had an
      elevated incidence of BD from 19 to 23 years, while adolescents with SUB
      exhibited elevated rates of MDD and anxiety disorders in young adulthood. BD and
      SUB groups both had elevated rates of antisocial symptoms and borderline
      personality symptoms. Compared to the ND group, adolescents with BD and SUB both
      showed significant impairment in psychosocial functioning and had higher mental
      health treatment utilization at age 24 years of age. The relatives of adolescents
      with BD and SUB had elevated rates of MDD and anxiety disorders. The relatives of
      SUB probands had elevated BD, while the relatives of BD had elevated rates of SUB
      and borderline symptoms. CONCLUSIONS: Adolescent BD showed significant continuity
      across developmental periods and was associated with adverse outcomes during
      young adulthood. Adolescent SUB was also associated with adverse outcomes in
      young adulthood, but was not associated with an increased incidence of BD. Due to
      high rates of comorbidity with other disorders, definitive conclusions regarding
      the specific clinical significance of SUB must await studies with larger numbers
      of 'pure' SUB cases.

PMID- 11249807
TI  - Present and future role of Mental Illness Advocacy Associations in the management
      of the mentally ill: realities, needs and hopes at the edge of the third
      millennium.
AB  - OBJECTIVE: The purpose of the present review is the analysis of the development
      and current status of the Mental Illness Advocacy Movement in the USA and in
      Europe, as well as of the role such a movement is playing in the management of
      the mentally ill. METHODS: Information on the issue has been collected via
      literature search and several personal inquiries and contacts with different
      Mental Illness Advocacy Groups in the USA and in Europe. RESULTS: The findings
      indicate that the Mental Illness Advocacy Movement is very alive and in full
      growth. Its role in the management of the mentally ill has become more and more
      important over the years. In several countries, it makes it possible to overcome
      some of the deficiencies of the National or Private Health Services. Thanks to
      the actions of the various Mental Illness Advocacy Groups, today, patients and
      families are more and better informed of their conditions and their rights. In
      many cases, this results in earlier diagnosis, better compliance and better
      outcomes. However, despite significant improvement in the status of the mentally
      ill patient, much still remains to be done. CONCLUSIONS: We need an improved
      dialogue with mental heath providers, public administrators, mental health policy
      makers, mass media and politicians. The dialogue between primary care team and
      the specialist must also be improved. A global alliance for action is needed to
      ensure better and more available services to those who suffer from mental
      disorders.

PMID- 11249808
TI  - The rise and fall of Mir.

PMID- 11249809
TI  - Were there duikers in ancient Egypt?

PMID- 11249811
TI  - Math melodrama rings of reality.

PMID- 11249810
TI  - Newest member of the NIH family.

PMID- 11249812
TI  - Fundamental criteria of Nobel Prizes.

PMID- 11249813
TI  - In search of the first Europeans.

PMID- 11249815
TI  - Pre-Clovis sites fight for acceptance.

PMID- 11249814
TI  - The riddle of coexistence.

PMID- 11249816
TI  - Clovis first.

PMID- 11249817
TI  - Tracking the sexes by their genes.

PMID- 11249818
TI  - The peopling of the Pacific.

PMID- 11249819
TI  - Genealogical and evolutionary inference with the human Y chromosome.
AB  - Population genetics has emerged as a powerful tool for unraveling human history.
      In addition to the study of mitochondrial and autosomal DNA, attention has
      recently focused on Y-chromosome variation. Ambiguities and inaccuracies in data
      analysis, however, pose an important obstacle to further development of the
      field. Here we review the methods available for genealogical inference using Y
      chromosome data. Approaches can be divided into those that do and those that do
      not use an explicit population model in genealogical inference. We describe the
      strengths and weaknesses of these model-based and model-free approaches, as well
      as difficulties associated with the mutation process that affect both methods. In
      the case of genealogical inference using microsatellite loci, we use coalescent
      simulations to show that relatively simple generalizations of the mutation
      process can greatly increase the accuracy of genealogical inference. Because
      model-free and model-based approaches have different biases and limitations, we
      conclude that there is considerable benefit in the continued use of both types of
      approaches.

PMID- 11249820
TI  - Genetic clues to dispersal in human populations: retracing the past from the
      present.
AB  - Ongoing debate about proper interpretation of DNA sequence polymorphisms and
      their ability to reconstruct human population history illustrates a important
      change in perspective that we have achieved in the past 20 years of population
      genetics. To what extent does the history of a locus represent the history of a
      population? Tools originally developed for molecular systematics, where genetic
      lineages have been separated by speciation events, are routinely applied to the
      analysis of variation within our species, with conflicting results. Because of
      automated technologies and linkage analysis, we are poised to harvest a wealth of
      information about our past, if we are successful in moving beyond a current
      polarization regarding models of human evolution. Rather than just suggesting
      that true resolution will only come by considering fossil or archaeological
      evidence, the realistic and appropriate application of genetic models for
      analysis of population structure is also necessary. Three examples from different
      dispersal events are highlighted here.

PMID- 11249821
TI  - Paleolithic technology and human evolution.

PMID- 11249822
TI  - Mechanisms responsible for cross-resistance and dichotomous resistance among the
      quinolones.
AB  - Resistance to the quinolones almost always arises from the accumulation of
      mutations in chromosomal genes responsible for the drug targets, permeability, or
      active efflux. This resistance can be depicted as a stepwise process in which
      each step, represented by separate mutations, diminishes susceptibility on
      average 4- to 8-fold. The precise path followed in this stepwise process differs
      with the quinolone that selects resistance as well as the organism involved. At
      each step, the influence of each mutation on susceptibility to other quinolones
      not used in the selection process varies greatly, and a pattern of either cross
      resistance or dichotomous resistance may be seen. From an understanding of the
      stepwise process by which resistance to the quinolones evolves, it is possible to
      use an 8-fold rule to predict which compounds may provide effective therapy for a
      given infection and be least likely to select for resistance.

PMID- 11249823
TI  - Mechanisms of action of antimicrobials: focus on fluoroquinolones.
AB  - Five bacterial targets have been exploited in the development of antimicrobial
      drugs: cell wall synthesis, protein synthesis, ribonucleic acid synthesis,
      deoxyribonucleic acid (DNA) synthesis, and intermediary metabolism. Because
      resistance to drugs that interact with these targets is widespread, new
      antimicrobials and an understanding of their mechanisms of action are vital. The
      fluoroquinolones are the only direct inhibitors of DNA synthesis; by binding to
      the enzyme-DNA complex, they stabilize DNA strand breaks created by DNA gyrase
      and topoisomerase IV. Ternary complexes of drug, enzyme, and DNA block progress
      of the replication fork. Cytotoxicity of fluoroquinolones is likely a 2-step
      process involving (1) conversion of the topoisomerase-quinolone-DNA complex to an
      irreversible form and (2) generation of a double-strand break by denaturation of
      the topoisomerase. The molecular factors necessary for the transition from step 1
      to step 2 remain unclear, but downstream pathways for cell death may overlap with
      those used by other bactericidal antimicrobials. Studies of fluoroquinolone
      resistant mutants and purified topoisomerases indicate that many quinolones have
      differing activities against the two targets. Drugs with similar activities
      against both targets may prove less likely to select de novo resistance.

PMID- 11249824
TI  - Comparative in vitro and in vivo activity of the C-8 methoxy quinolone
      moxifloxacin and the C-8 chlorine quinolone BAY y 3118.
AB  - The C-8 methoxy quinolone moxifloxacin is highly bactericidal against wild-type
      and first-step gyrase- and topoisomerase IV-resistant mutants. This finding led
      to the hypothesis that the C-8 methoxy group may lower the propensity for
      resistance development compared with quinolones possessing different substituents
      at the C-8 position. Therefore, resistance development of the C-8 methoxy
      quinolone moxifloxacin was compared with that of its structural analogue BAY y
      3118 (chlorine moiety at the C-8 position), with Staphylococcus aureus used as
      the test organism. The spontaneous emergence of resistance was quantified by
      counting the number of colonies growing on drug-free medium compared with
      moxifloxacin- or BAY y 3118-containing media. The multistep emergence of
      quinolone resistance was encountered by growing S. aureus over 8 passages in drug
      containing medium. Human serum concentrations were simulated in an in vitro model
      over 84 h (dosing every 24 h), and total and resistant S. aureus were quantified.
      Spontaneous mutation frequencies of 6x10-11 for moxifloxacin and 4x10-7 for BAY y
      3118 were observed. Multistep resistance to moxifloxacin developed slowly (2-fold
      rise) but rapidly against BAY y 3118 (>16-fold rise). No resistance against
      moxifloxacin developed in this model, whereas resistance to BAY y 3118 began to
      develop after 4 h. Thus, as the C-8 moiety was the only difference, the 8-methoxy
      group on moxifloxacin appeared to significantly lower the propensity for
      quinolone resistance development.

PMID- 11249825
TI  - Penicillin-resistant streptococcus pneumoniae: review of moxifloxacin activity.
AB  - Streptococcus pneumoniae is a significant pathogen of respiratory tract
      infections such as pneumonia, sinusitis, meningitis, and acute otitis media.
      Rising incidences of antimicrobial resistance among pneumococcal strains reported
      worldwide have led to research into and development of advanced antibacterials
      with improved gram-positive activity. Moxifloxacin, a new 8-methoxy quinolone,
      has been tested against a variety of S. pneumoniae strains, including penicillin
      sensitive, intermediately resistant to penicillin, and penicillin-resistant
      strains. We review the preclinical data corroborated by the available clinical
      experience to demonstrate moxifloxacin's activity against S. pneumoniae strains,
      irrespective of penicillin susceptibility.

PMID- 11249826
TI  - Comparative in vitro activity of moxifloxacin by E-test against Streptococcus
      pyogenes.
AB  - Macrolides are currently used to treat Streptococcus pyogenes infections where
      allergy or resistance prevents the use of penicillin. However, growing macrolide
      resistance is now seen worldwide, with rates of 5%-40% being reported. In this
      context it is therefore important to have other therapeutic options. The aim of
      this study was to ascertain the potential role of moxifloxacin, a third
      generation fluoroquinolone, in the treatment of infections caused by group A S.
      pyogenes. The antimicrobial susceptibilities of S. pyogenes isolated from 197
      adult patients with pharyngotonsillitis were analyzed by the E-test. Twelve
      percent of the isolates were resistant to macrolides, and 5% showed diminished
      susceptibility toward penicillin; none of the strains were resistant to
      cefotaxime or to moxifloxacin (90% minimum inhibitory concentration, 0.25
      microg/mL). Therefore, moxifloxacin may be a therapeutic option in the management
      of S. pyogenes infections when penicillin cannot be used or when macrolide
      resistance may be a local issue. Clinical studies of moxifloxacin in
      pharyngotonsillitis are warranted.

PMID- 11249827
TI  - Pharmacodynamics of moxifloxacin and levofloxacin against Staphylococcus aureus
      and Staphylococcus epidermidis in an in vitro pharmacodynamic model.
AB  - An in vitro pharmacokinetic model was used to compare the pharmacodynamics of
      moxifloxacin and levofloxacin against 3 Staphylococcus aureus and 3
      Staphylococcus epidermidis strains. Logarithmic-phase cultures were inoculated
      into the peripheral compartment of hollow-fiber cartridges and exposed to the
      peak serum concentrations achieved in humans with oral doses of moxifloxacin (400
      mg) and levofloxacin (500 mg). Drugs were added at 0 and 24 h, elimination
      kinetics were simulated, and changes in viable bacterial counts were evaluated
      over the course of 36 h. Moxifloxacin was bactericidal against all 6
      staphylococci (times to 99.9% kill, 1-3 h). Against most strains, bacterial
      killing continued through 36 h, with total kills exceeding 5.5 logs. Levofloxacin
      was bactericidal against 5 of the strains, with similar times to 99.9% kill. In
      contrast to moxifloxacin, however, resistant subpopulations emerged in 4 strains
      during therapy with levofloxacin, and this could have important implications for
      treatment of staphylococcal infections. These in vitro observations warrant the
      clinical evaluation of moxifloxacin in the treatment of staphylococcal
      infections.

PMID- 11249828
TI  - What have we learned from pharmacokinetic and pharmacodynamic theories?
AB  - Pharmacokinetic characteristics and pharmacodynamic properties dictate
      antimicrobial response and, along with natural immune responses, clinical
      outcomes. As new agents are developed with long half-lives, we will lose the
      ability to differentiate between concentration-dependent and time-dependent
      properties. The area under the inhibitory concentration curve (AUIC) defines drug
      regimens as a ratio of drug exposure to minimum inhibitory concentration (MIC)
      and allows them to be compared with each other. With AUIC and agents with long
      half-lives, these comparisons are possible regardless of chemical classification
      or concentration or time-dependent activity. Historical examples of reduced drug
      exposure from decreased doses (i.e., cefaclor, clarithromycin, and
      ciprofloxacin), and thus low AUIC values, directly correlate with drug
      resistance. In the face of rising MICs (as is occurring worldwide with
      Streptococcus pneumoniae), close attention to appropriate dosing and
      concentration above the MIC may delay and potentially even prevent antibiotic
      resistance. Creating selective pressure on reliable antibiotics by
      inappropriately reducing their doses will undoubtedly challenge these agents and
      may destroy entire drug classes with similar mechanisms of action or resistance.

PMID- 11249829
TI  - Profile of moxifloxacin drug interactions.
AB  - We report a brief description of the interaction profile of moxifloxacin. After
      oral administration, the absorption of moxifloxacin was unaffected by ranitidine
      or by food consumption. Drugs containing multivalent cations (e.g., Mg(++),
      Al(+++), and Fe(++), but not Ca(++)) impaired absorption. No clinically relevant
      effect of moxifloxacin was seen on the pharmacokinetics of digoxin under
      combination steady state conditions. Also, moxifloxacin did not affect the
      pharmacokinetics of theophylline or vice versa. This result, plus further data
      proving lack of interaction with glyburide, warfarin, and oral contraceptives,
      confirms the absence of metabolic interactions involving the cytochrome P-450
      system, as previously reported. Concomitant administration of probenecid did not
      affect the elimination of moxifloxacin. Moxifloxacin thus has a unique drug
      interaction profile that is advantageous for its safe use.

PMID- 11249830
TI  - Evaluation of the clinical microbiology profile of moxifloxacin.
AB  - Moxifloxacin is a new broad-spectrum antibacterial agent for treatment of
      respiratory tract infection of pathogens, including the major pathogens isolated
      in respiratory tract infections. The pharmacokinetic and pharmacodynamic
      properties of moxifloxacin are: excellent bioavailability, long half-life, and
      superior tissue penetration. Consequently, the 90% minimum inhibitory
      concentration (MIC(90)) values exhibited by moxifloxacin are generally lower than
      the concentrations of moxifloxacin found in circulation and in pulmonary tissues
      after a standard 400-mg dose given for up to 30 h. The relationship between
      moxifloxacin MIC(90) values and clinical response was investigated. The results
      of 13 clinical trials, performed in 30 countries between 1997 and 1998 and
      comprising 2618 patients treated with moxifloxacin or a comparator drug, were
      reviewed. Overall, 94% clinical success and 95% bacterial eradication was
      observed with moxifloxacin. These results were equivalent or superior to results
      seen with the comparator drugs. Clinical response rates and bacterial eradication
      rates with moxifloxacin were not significantly affected by bacterial resistance
      to other antibiotics (i.e., penicillin, clarithromycin, or amoxicillin). The
      majority (89%-97%) of the different bacterial strains with MICs for moxifloxacin
      < or =2 mg/L were successfully eradicated. In conclusion, moxifloxacin has potent
      in vivo bactericidal activity, and pathogen sensitivity to moxifloxacin is in
      accordance with US Food and Drug Administration and European suggested breakpoint
      values.

PMID- 11249831
TI  - Clinical perspectives on new antimicrobials: focus on fluoroquinolones.
AB  - Respiratory tract infections are the most common infectious presentation in the
      community and hospital settings and are a major cause of morbidity and mortality
      worldwide. Recently, newer fluoroquinolones have been recommended for the
      treatment of these infections. Among them, moxifloxacin shows improved activity
      against gram-positive pathogens, has maintained potency against gram-negative
      organisms, and shows activity against atypical pathogens and anaerobes.
      Moxifloxacin also has excellent in vitro activity against strains resistant to
      penicillin, erythromycin, and other fluoroquinolones, such as levofloxacin.
      Moxifloxacin has demonstrated clinical efficacy rates of 90%-95% in clinical
      trials in community-acquired pneumonia, acute exacerbations of chronic
      bronchitis, and acute sinusitis. In these trials, moxifloxacin demonstrated no
      serious or unexpected adverse effects. Development of resistance appears to be
      slower for moxifloxacin than for several other fluoroquinolones, making
      moxifloxacin a good treatment choice. The pharmacodynamics of moxifloxacin
      support once-daily oral therapy of short duration, providing convenience,
      compliance, and safety advantages.

PMID- 11249832
TI  - Antimicrobial safety and tolerability: differences and dilemmas.
AB  - The adverse drug reactions associated with antimicrobials have become a topic of
      major importance and concern in the last few years. Antimicrobial toxicity may
      take many forms, varying from mild, transient phenomena to dramatic, life
      threatening events such as seizures or cardiac arrhythmias. We review the
      toxicity of antimicrobials in general and of the fluoroquinolones in particular
      and attempt to explain the adverse events by use of structure-adverse event
      relationships where possible. There are currently 5 main mechanisms that can be
      invoked to explain antimicrobial toxicity: direct effects, hypersensitivity,
      changes in microbial flora, drug interactions, and microbial lysis. The adverse
      drug reactions seen with fluoroquinolones are explained on the basis of these 5
      mechanisms. The various organ systems affected by the fluoroquinolones are
      considered; then individual members of the fluoroquinolone class are reviewed.
      The unexpected and dramatic problems encountered with temafloxacin and
      trovafloxacin are discussed as well.

PMID- 11249833
TI  - Functional consequences of a novel middle ear adaptation in the central African
      frog Petropedetes parkeri (Ranidae).
AB  - During the breeding season, each tympanic membrane of males of the Old World
      treefrog Petropedetes parkeri is decorated with a single, prominent, fleshy
      tympanic papilla. The tympanic papilla, located dorsally on the tympanic
      membrane, is covered by an epidermal surface and is composed of non-ossified,
      spongiform tissue containing a number of globular, fluid-filled vesicles found at
      highest density near the papillar tip. These vesicles appear to have exit pores
      and are probably simple alveolar exocrine glands. Injecting sound into the
      pressurized vocal cavity of the male and measuring the vibration velocity
      response of the tympanic membrane revealed that from 0.3 to 2.0 kHz the tympanic
      papilla velocity amplitude is on average 20 dB lower than that of a point
      diametrically opposite on the ventral half of the tympanic membrane. The close
      agreement between the dominant frequency of the call and the frequency of the
      maximum spectral peak of the Fast Fourier Transform of the impulse response of
      the eardrum is consistent with the use of the eardrum in this species both as a
      call receiver and as a call radiator, similar to the function suggested for the
      eardrum of the male bullfrog Rana catesbeiana. Unexpectedly, surgically removing
      the tympanic papilla lowered the frequency of the peak vibrational amplitude,
      testifying to the importance of membrane tension as a dominant factor in the
      vibratory behavior of the eardrum. During normal positive-pressure breathing, the
      tympanic papillae move conspicuously, suggesting a possible role as a visual
      signal.

PMID- 11249834
TI  - Spatio-temporal gait characteristics of level and vertical locomotion in a ground
      dwelling and a climbing gecko.
AB  - The effects of incline (vertical versus horizontal) on spatio-temporal gait
      characteristics (stride and step length, frequency, duty factor, degree of
      sprawling) were measured over a range of speeds in a ground-dwelling (Eublepharis
      macularius) and a climbing (Gekko gecko) species of gecko. Surprisingly, the
      climbing species also performs very well when moving on the horizontal
      substratum. In the present experiments, climbing speeds ranged from 0.6 to 1.2 m
      s(-1), whereas speeds for level locomotion were between 0.6 and 1.8 m s(-1). In
      contrast, the vertical climbing capacities of the ground-dweller are limited
      (speeds below 0.1 m s(-1 )versus level speeds between 0.2 and 1.1 m s(-1)). In
      general, we demonstrate that very little adjustment in gait characteristics is
      made by either species when they are forced to move on their non-habitual
      substratum. Moreover, gait characteristics differ little between the species
      despite the clear differences in ecological niche. Higher level or climbing
      speeds are realized mainly (or exclusively in the case of level locomotion in G.
      gecko) by increasing stride frequency. Stride lengths and duty factors vary with
      speed in the ground-dweller, but not in the climbing species. Step length and the
      degree of sprawling are speed-independent (except for hind-limb sprawling in G.
      gecko on the level). It is argued that this common strategy suits climbing (fixed
      spatial variables, no floating phases) rather than level locomotion.

PMID- 11249835
TI  - Evidence for a form of adrenergic response to stress in the mollusc Crassostrea
      gigas.
AB  - Catecholamines and pro-opiomelanocortin (POMC)-derived peptides, some of the
      central regulators of the stress-response systems of vertebrates, are also
      present in invertebrates. However, studies are needed to determine how these
      hormones participate in the organisation of neuroendocrine stress-response axes
      in invertebrates. Our present work provides evidence for the presence of an
      adrenergic stress-response system in the oyster Crassostrea gigas. Noradrenaline
      and dopamine are released into the circulation in response to stress. Storage and
      release of these hormones take place in neurosecretory cells presenting
      morphological and biochemical similarities with vertebrate chromaffin cells. Both
      in vivo and in vitro experiments showed that applications of the
      neurotransmitters acetylcholine or carbachol caused no significant release of
      noradrenaline or dopamine. Moreover, the nicotinic antagonists hexamethonium and
      &agr; -bungarotoxin and the muscarinic antagonist atropine caused no significant
      inhibition of catecholamine release in stressed oysters. Adrenocorticotropic
      hormone (ACTH) induced a significant release of noradrenaline, but the release of
      dopamine in response to ACTH was not significant. These results suggest that,
      unlike that of vertebrates, the adrenergic stress-response system of oysters is
      not under the control of acetylcholine and that other factors, such as the
      neuropeptide ACTH, might control this system.

PMID- 11249836
TI  - Defensive inking in Aplysia spp: multiple episodes of ink secretion and the
      adaptive use of a limited chemical resource.
AB  - The seahare Aplysia spp. extracts many of its defensive chemicals from its red
      seaweed diet, including its purple ink, which is an effective deterrent against
      predators such as anemones and crabs. It is believed that the inking behavior is
      a high-threshold, all-or-none fixed act that nearly completely depletes the
      seahare of its ink supply. If a seahare depletes its gland of ink, it must seek
      out a source of red seaweed and then feed for at least 2 days to replenish its
      ink supply. This suggests that the animal would not be able to deploy ink more
      than once in rapid succession in response to successive attacks from one or more
      predators. However, we found that Aplysia spp. can secrete ink in response to
      three or more successive stimulations with (i) anemone tentacles, (ii) a
      mechanical stimulus, consisting of grabbing and lifting the animal from the
      substratum, or (iii) a noxious electric shock. A spectro-photometric measure of
      ink secretion showed that only approximately 48 % of the gland's releasable ink
      reserves are deployed initially. Thus, deployment of this defensive chemical is
      not strictly all-or-nothing, although the trigger mechanism is. Moreover, the
      animal tends to secrete a relatively fixed proportion (30--50 %) of its available
      ink reserves even after its gland has been depleted to approximately half its
      initial content. Since an animal need only use a proportion of its ink reserves
      to deter an attacker effectively, the inking behavior is adaptive in its
      economical use of a limited resource.

PMID- 11249837
TI  - Intestinal peptides as circulating hormones: release of tachykinin-related
      peptide from the locust and cockroach midgut.
AB  - Tachykinin-related peptides (TRPs) in the locust Locusta migratoria and the
      cockroach Leucophaea maderae have stimulatory effects on some muscles that are
      not innervated by TRP-containing neurons. Thus, these tissues may be affected by
      circulating TRPs. Here, we have investigated whether the midgut is the source of
      circulating TRPs. TRP-immunoreactive material in the locust midgut is found only
      in the endocrine cells of the gut epithelium. In both species of insect, the
      endocrine cells contain several isoforms of TRPs, as determined by
      immunocytochemistry and a combination of chromatography (HPLC) and enzyme
      immunoassay (ELISA). The release of TRPs was investigated by ELISA using isolated
      midguts of the locust and cockroach. Elevated levels of K(+) in the bathing
      saline induced the release of TRP from the midgut of both species. To examine the
      release of TRPs into the circulation in vivo, we measured haemolymph levels of
      TRPs in fed and starved locusts. The concentration of TRP-immunoreactive material
      in fed locusts was estimated to be 0.15 nmol l(-1), and this increased
      approximately fourfold in insects starved for 24 h. In accordance with this
      observation, the content of TRP-immunoreactive material in the midgut was lower
      in starved locusts than in fed locusts. Although part of the increased blood
      concentration of TRPs may be due to reduced blood volume, our data suggest that
      TRPs are released as hormones from the midgut of the locust and cockroach and
      that this release may be linked to nutritional status.

PMID- 11249838
TI  - Tympanic membrane oscillations and auditory receptor activity in the stridulating
      cricket Gryllus bimaculatus.
AB  - The ears of stridulating crickets are exposed to loud self-generated sounds that
      might desensitise the auditory system and reduce its responsiveness to
      environmental sounds. We examined whether crickets prevent self-induced auditory
      desensitisation, and measured the responsiveness of the peripheral auditory
      system of the cricket (acoustic spiracle, tympanic membrane and tympanic nerve)
      during pharmacologically induced sonorous (two-winged) and silent (one-winged)
      stridulation. The acoustic spiracles remained open during stridulation, so the
      self-generated auditory signal had full access to both the external side and the
      internal side of the tympanic membrane. When the spiracles shut in resting
      crickets, the responsiveness of the tympanic membrane to acoustic stimuli varied
      according to the phase of ventilation and was minimal during expiration. The
      tympanic membrane oscillated in phase with the self-generated sounds during
      sonorous chirps and did not oscillate during silent chirps. In both sonorously
      and silently singing crickets, the responses of the tympanic membrane to acoustic
      stimuli were identical during the chirps and the chirp intervals. Bursts of
      activity were recorded in the tympanic nerve during sonorous chirps; however,
      activity was minor during silent chirps. In sonorously and in silently singing
      crickets, the summed nerve response to acoustic stimuli in the chirp intervals
      was the same as in resting crickets. The response to stimuli presented during the
      syllable intervals of sonorous chirps was slightly reduced compared with the
      response in the chirp intervals as a consequence of receptor habituation. In
      silently singing crickets, acoustic stimuli elicited the same summed nerve
      response during chirps and chirp intervals. These data indicate that in the
      cricket no specific mechanism acts to reduce the responsiveness of the peripheral
      auditory pathway during stridulation.

PMID- 11249839
TI  - Mechanisms of frequency-specific responses of omega neuron 1 in crickets
      (Teleogryllus oceanicus): a polysynaptic pathway for song?
AB  - In crickets (Teleogryllus oceanicus), the auditory interneuron omega neuron 1
      (ON1) responds to sounds over a wide range of frequencies but is most sensitive
      to the frequency of conspecific songs (4.5 kHz). Response latency is longest for
      this same frequency. We investigate the mechanisms that might account for the
      longer latency of ON1 to cricket-like sounds. Intracellular recordings revealed
      no evidence for appropriately timed postsynaptic inhibition of ON1 that might
      increase its latency, nor was latency affected by picrotoxin. The onset of
      excitatory postsynaptic potentials (EPSPs) was delayed for 4.5 kHz stimuli
      compared with ultrasound stimuli, pointing to a presynaptic locus for the latency
      difference. When ON1 is stimulated with high frequencies, discrete, apparently
      unitary EPSPs can be recorded in its dendrite, and these are latency-locked to
      spikes recorded simultaneously in the auditory nerve. This suggests that input to
      ON1 from high-frequency-tuned auditory receptor neurons is monosynaptic. In
      agreement with this, brief ultrasound stimuli evoke a single, short-latency EPSP
      in ON1. In contrast, the EPSP evoked by a brief 4.5 kHz stimulus consists of an
      early component, similar in latency to that evoked by ultrasound and possibly
      evoked by ultrasound-tuned receptors, and a later, dominant component. We
      interpret the early peak as arising from a monosynaptic afferent pathway and the
      late peak from a polysynaptic afferent pathway. Multiple-peak EPSPs, with timing
      similar to those evoked by sound stimuli, were also evoked by electrical
      stimulation of the auditory nerve.

PMID- 11249840
TI  - Induction of a non-rhythmic motor pattern by nitric oxide in hatchling Rana
      temporaria embryos.
AB  - Nitric oxide (NO) is a ubiquitous neuromodulator with a diverse array of
      functions in a variety of brain regions, but a role for NO in the generation of
      locomotor activity has yet to be demonstrated. The possibility that NO is
      involved in the generation of motor activity in embryos of the frog Rana
      temporaria was investigated using the NO donors S-nitroso-n-acetylpenicillamine
      (SNAP; 100--500 micromol l(-1)) and diethylamine nitric oxide complex sodium
      (DEANO; 25--100 micromol l(-1)). Immobilised Rana temporaria embryos generate a
      non-rhythmic 'lashing' motor pattern either spontaneously or in response to
      dimming of the experimental bath illumination. Bath-applied NO donors triggered a
      qualitatively similar motor pattern in which non-rhythmic motor bursts were
      generated contra- and ipsilaterally down the length of the body. The inactive
      precursor of SNAP, n-acetyl-penicillamine (NAP), at equivalent concentrations did
      not trigger motor activity. NO donors failed to initiate swimming and had no
      measurable effects on the parameters of swimming induced by electrical
      stimulation. Intracellular recordings with potassium-acetate-filled electrodes
      revealed that the bursts of ventral root discharge induced by NO donors were
      accompanied by phasic depolarisations in motor neurons. During the inter-burst
      intervals, periods of substantial membrane hyperpolarization below the normal
      resting potential were observed, presumably coincident with contralateral ventral
      root activity. With KCl-filled electrodes, inhibitory potentials were strongly
      depolarising, suggesting that inhibition was Cl(-)-dependent. The synaptic drive
      seen in motor neurons after dimming of the illumination was very similar to that
      induced by the NO donors. NADPH-diaphorase histochemistry identified putative
      endogenous sources of NO in the central nervous system and the skin. Three
      populations of bilaterally symmetrical neurons were identified within the
      brainstem. Some of these neurons had contralateral projections and many had
      axonal processes that projected to and entered the marginal zones of the spinal
      cord, suggesting that they were reticulospinal.

PMID- 11249843
TI  - Consequences of transient fluid forces for compliant benthic organisms.
AB  - The diversity of form among benthic marine plants and animals on rocky coasts is
      remarkable. Stiff and strong organisms grow alongside others that are compliant
      and flimsy. Given the severity of wave action on many shores and thus the
      potential for the imposition of large hydrodynamic forces, this immediately
      raises the question of how, from this overall spectrum of designs, flexible and
      weak organisms survive. A number of explanations have been proposed, most
      emphasizing one or more of several possible advantages of deformability. Here, we
      explore quantitatively two of the more common of these explanations: (i) that
      strength can be traded against extensibility in allowing stretchy organisms to
      withstand transient wave forces, and (ii) that greater compliance (and thus
      longer organism response times) allows universally for the amelioration of brief
      loads. We find that, although these explanations contain kernels of validity and
      are accurate for a subset of conditions, they are not as general as has often
      been assumed.

PMID- 11249842
TI  - A study of helical and planar waves on sea urchin sperm flagella, with a theory
      of how they are generated.
AB  - When the spermatozoon of Echinus esculentus swims in sea water containing methyl
      cellulose (viscosity 1.5--4 Pa s), its flagellum may generate either a helical or
      a planar waveform, each type being stable. The helical wave, which is dextral, is
      complicated by the concurrent passage of miniature waves along it. These
      miniature waves have a pulsatile origin in the neck region of the spermatozoon.
      Our videotape analysis indicates that there are two pulses of mechanical activity
      for each true cycle of the helical wave. (The true helical frequency was obtained
      from the apparent wave frequency and the roll frequency of the sperm head, the
      latter being detectable in some sperm when lit stroboscopically.) The planar wave
      has a meander shape. During the propagation of planar waves, the sliding
      displacements are adjustable in either direction; moribund flagella can undergo
      unrestricted sliding. The planar waves are, in fact, exactly planar only at
      interfaces. Otherwise, there tend to be torsions in the interbend segments
      between planar bends. Mechanical stimulation of the flagellum can cause a sudden
      transition from the helical to the planar waveform. To account for the two modes
      of beating, we advance the hypothesis that circumferential linkages yield beyond
      a threshold strain. Whether this yield point is exceeded, we suggest, depends
      upon the balance between the active shear force and the external viscosity (among
      other factors). We propose that a subthreshold force originates in one array and
      then triggers the other dynein arrays circumferentially, but unidirectionally,
      around the base of the flagellum; whereas a suprathreshold force provokes bi
      directional circumferential triggering. These may be the two patterns of
      activation that result in helical and planar waveforms, respectively. The
      transition from helical to planar bending may result from an increment in the
      force produced by the dynein motors. The pulsatile origin of the helical wave
      resembles behaviour described previously for spermatozoa of Ciona intestinalis
      and of the quail Coturnix coturnix.

PMID- 11249841
TI  - Opposing actions of nitric oxide on synaptic inputs of identified interneurones
      in the central nervous system of the crayfish.
AB  - Little is known of the action of nitric oxide (NO) at the synaptic level on
      identified interneurones in local circuits that process mechanosensory signals.
      Here, we examine the action of NO in the terminal abdominal ganglion of the
      crayfish Pacifastacus leniusculus, where it has modulatory effects on the
      synaptic inputs of 17 identified ascending interneurones mediated by electrical
      stimulation of a sensory nerve. To analyse the role of NO in the processing of
      sensory signals, we bath-applied the NO donor SNAP, the NO scavenger PTIO, the
      nitric oxide synthase (NOS) inhibitor l-NAME, the NOS substrate l-arginine, a
      cyclic GMP (cGMP) analogue, 8-Br-cGMP, and the soluble guanylate cyclase (sGC)
      inhibitor ODQ. The effects of these chemicals on the synaptic inputs of the
      interneurones could be divided into two distinct classes. The NO donor SNAP
      enhanced the inputs to one class of interneurone (class 1) and depressed those to
      another (class 2). Neither the inactive isomer NAP nor degassed SNAP had any
      effect on the inputs to these same classes of interneurone. The NO scavenger PTIO
      caused the opposite effects to those of the NO donor SNAP, indicating that
      endogenous NO may have an action in local circuits. Preventing the synthesis of
      NO using l-NAME had the opposite effect to that of SNAP on each response class of
      interneurone. Increasing the synthesis of endogenous NO by applying l-arginine
      led to effects on both response classes of interneurone similar to those of SNAP.
      Taken together, these results suggested that NO was the active component in
      mediating the changes in amplitude of the excitatory postsynaptic potentials.
      Finally, the effects of 8-Br-cGMP were similar to those of the NO donor,
      indicating the possible involvement of a NO-sensitive guanylate cyclase. This was
      confirmed by preventing the synthesis of cGMP by sGC using ODQ, which caused the
      opposite effects to those of 8-Br-cGMP on the two response classes of
      interneurone. The results indicate that a NO--cGMP signal transduction pathway,
      in which NO regulates transmitter release from mechanosensory afferents onto
      intersegmental ascending interneurones, is probably present in the local circuits
      of the crayfish.

PMID- 11249844
TI  - Seasonal hypothermia in a large migrating bird: saving energy for fat deposition?
AB  - We have tested the hypothesis that a large (2 kg) migratory bird, such as the
      barnacle goose Branta leucopsis, becomes hypothermic before its autumn migration,
      when food is not scarce, but when it is necessary to conserve and/or store energy
      in the form of fat. Abdominal temperature (T(ab)) was measured in wild geese
      using an implanted data logger. Commencing a few days before and continuing until
      approximately 20 days after the start of their autumn migration, mean daily T(ab)
      fell progressively by 4.4 degrees C. Thus, it is suggested that, rather than
      increasing the rate of pre-migratory fattening, the energy saved as a result of
      this hypothermia reduces the rate at which fat is used and thus enables its more
      rapid replacement following and, possibly during, migration. The energy saved may
      also be used for the replacement of non-fat tissues such as the locomotory
      muscles and gastro-intestinal tract. These observations are the first of their
      kind from birds in their natural environment and, together with other data,
      demonstrate that hypothermia in endotherms is not necessarily related to
      extremely low environmental temperature, to shortage of food or to the resting
      phase of the daily cycle. The data also highlight the relationship between
      hypothermia and fat deposition over extended periods in relatively large,
      endothermic animals and may have some relevance to obesity in humans.

PMID- 11249845
TI  - Slow muscle power output of yellow- and silver-phase European eels (Anguilla
      anguilla L.): changes in muscle performance prior to migration.
AB  - Eels swim in the anguilliform mode in which the majority of the body axis
      undulates to generate thrust. For this reason, muscle function has been
      hypothesised to be relatively uniform along the body axis relative to some other
      teleosts in which the caudal fin is the main site of thrust production. The
      European eel (Anguilla anguilla L.) has a complex life cycle involving a lengthy
      spawning migration. Prior to migration, there is a metamorphosis from a yellow
      (non-migratory) to a silver (migratory) life-history phase. The work loop
      technique was used to determine slow muscle power outputs in yellow- and silver
      phase eels. Differences in muscle properties and power outputs were apparent
      between yellow- and silver-phase eels. The mass-specific power output of silver
      phase slow muscle was greater than that of yellow-phase slow muscle. Maximum slow
      muscle power outputs under approximated in vivo conditions were 0.24 W kg(-1) in
      yellow-phase eel and 0.74 W kg(-1) in silver-phase eel. Power output peaked at
      cycle frequencies of 0.3--0.5 Hz in yellow-phase slow muscle and at 0.5--0.8 Hz
      in silver-phase slow muscle. The time from stimulus offset to 90 % relaxation was
      significantly greater in yellow- than in silver-phase eels. The time from
      stimulus onset to peak force was not significantly different between life-history
      stages or axial locations. Yellow-phase eels shifted to intermittent bursts of
      higher-frequency tailbeats at a lower swimming speed than silver-phase eels. This
      may indicate recruitment of fast muscle at low speeds in yellow-phase eels to
      compensate for a relatively lower slow muscle power output and operating
      frequency.

PMID- 11249846
TI  - The concept of cellular "fight-or-flight" reaction to stress.
AB  - As animals respond to environmental stress with a set of default reactions
      described as the "fight-or-flight" response, so do epithelial and endothelial
      cells when they are confronting stressors in their microenvironment. This review
      will summarize a growing body of data suggesting the existence of a set of
      stereotypical cellular reactions to stress, provide some examples of diseases
      that are characterized by excessive flight reactions, describe the cellular
      mechanisms whereby the fight-or-flight reaction is accomplished, as well as
      cellular mechanisms triggering either fight or flight. It is proposed that cell
      matrix adhesion is a sensitive indicator of the severity of stress. This
      indicator is interfaced with several default programs for cellular survival or
      death, thus dictating the fate of the cell. Some diagnostic and therapeutic
      applications of the concept, presently used and potentially useful, are outlined.
      The essential feature of this concept is its ability to categorize cellular
      events in terms of either type of default reaction, predict the details of each,
      and potentially exploit them clinically.

PMID- 11249847
TI  - Megalin and cubilin: synergistic endocytic receptors in renal proximal tubule.
AB  - The multiligand, endocytic receptors megalin and cubilin are colocalized in the
      renal proximal tubule. They are heavily expressed in the apical endocytic
      apparatus. Megalin is a 600-kDa transmembrane protein belonging to the low
      density lipoprotein-receptor family. The cytoplasmic tail contains three NPXY
      motifs that mediate the clustering in coated pits and are possibly involved in
      signaling functions. Cubilin, also known as the intestinal intrinsic factor
      cobalamin receptor, is a 460-kDa receptor with no transmembrane domain and no
      known signal for endocytosis. Because the two receptors bind each other with high
      affinity and colocalize in several tissues, it is highly conceivable that megalin
      mediates internalization of cubilin and its ligands. Both receptors are important
      for normal tubular reabsorption of proteins, including albumin. Among the
      proteins normally filtered in the glomeruli, cubilin has been shown to bind
      albumin, immunoglobulin light chains, and apolipoprotein A-I. The variety of
      filtered ligands identified for megalin include vitamin-binding proteins,
      hormones, enzymes, apolipoprotein H, albumin, and beta(2)- and alpha(1)
      microglobulin. Loss of these proteins and vitamins in the urine of megalin
      deficient mice illustrates the physiological importance of this receptor.

PMID- 11249848
TI  - Alternatively spliced isoform of apical Na(+)-K(+)-Cl(-) cotransporter gene
      encodes a furosemide-sensitive Na(+)-Cl(-)cotransporter.
AB  - In the absence of vasopressin, medullary thick ascending limb cells express a
      K(+)-independent, furosemide-sensitive Na(+)-Cl(-) cotransporter that is
      inhibited by hypertonicity. The murine renal specific Na(+)-K(+)-2 Cl(-)
      cotransporter gene (SLC12A1) gives rise to six alternatively spliced isoforms.
      Three feature a long COOH-terminal domain that encodes the butmetanide-sensitive
      Na(+)-K(+)-2 Cl(-) cotransporter (BSC1-9/NKCC2), and three with a short COOH
      terminal domain, known as mBSC1-A4, B4, or F4 (19). Here we have determined the
      functional characteristics of mBSC1-A4, as expressed in Xenopus laevis oocytes.
      When incubated at normal oocyte osmolarity (approximately 200 mosmol/kgH(2)O),
      mBSC1-4-injected oocytes do not express significant Na(+) uptake over H(2)O
      injected controls, and immunohistochemical analysis shows that the majority of
      mBSC1-4 protein is in the oocyte cytoplasm and not at the plasma membrane. In
      contrast, when mBSC1-4 oocytes are exposed to hypotonicity (approximately 100
      mosmol/kgH(2)O), a significant increase in Na(+) uptake but not in (86)Rb(+)
      uptake is observed. The increased Na(+) uptake is Cl(-) dependent, furosemide
      sensitive, and cAMP sensitive but K(+) independent. Sodium uptake increases with
      decreasing osmolarity between 120 and 70 mosmol/kgH(2)O (r = 0.95, P < 0.01).
      Immunohistochemical analysis shows that in hypotonic conditions mBSC1-A4 protein
      is expressed in the plasma membrane. These studies indicate that the mBSC1-A4
      isoform of the SLC12A1 gene encodes a hypotonically activated, cAMP- and
      furosemide-sensitive Na(+)-Cl(-) cotransporter. Thus it is possible that
      alternative splicing of the BSC1 gene could provide the molecular mechanism
      enabling the Na(+)-Cl(-)-to-Na(+)-K(+)-2Cl(-) switching in thick ascending limb
      cells.

PMID- 11249849
TI  - Influence of Ca(2+)-activated K(+) channels on rat renal arteriolar responses to
      depolarizing agonists.
AB  - Experiments were performed to evaluate the hypothesis that opening of Ca(2+)
      activated K(+) channels (BK(Ca) channels) promotes juxtamedullary arteriolar
      dilation and curtails constrictor responses to depolarizing agonists. Under
      baseline conditions, afferent and efferent arteriolar lumen diameters averaged
      23.4 +/- 0.9 (n = 36) and 22.8 +/- 1.1 (n = 13) microm, respectively. The
      synthetic BK(Ca) channel opener NS-1619 evoked concentration-dependent afferent
      arteriolar dilation. BK(Ca) channel blockade (1 mM tetraethylammonium; TEA)
      decreased afferent diameter by 15 +/- 3% and prevented the dilator response to 30
      microM NS-1619. ANG II (10 nM) decreased afferent arteriolar diameter by 44 +/-
      4%, a response that was reduced by 30% during NS-1619 treatment; however, TEA
      failed to alter afferent constrictor responses to either ANG II or arginine
      vasopressin. Neither NS-1619 nor TEA altered agonist-induced constriction of the
      efferent arteriole. Thus, although the BK(Ca) channel agonist was able to curtail
      afferent (but not efferent) arteriolar constrictor responses to ANG II, BK(Ca)
      channel blockade did not allow exaggerated agonist-induced arteriolar
      constriction. These observations suggest that the BK(Ca) channels evident in
      afferent arteriolar smooth muscle do not provide a prominent physiological brake
      on agonist-induced constriction under our experimental conditions.

PMID- 11249850
TI  - Chronic NOS inhibition reverses systemic vasodilation and glomerular
      hyperfiltration in pregnancy.
AB  - The chronic role of nitric oxide (NO), independent of prostaglandin synthesis, in
      the primary peripheral vasodilation, increased glomerular filtration rate (GFR),
      and renal plasma flow (RPF) in normal pregnancy remains to be defined. The
      purpose of the present study was to chronically inhibit NOS to return systemic
      vascular resistance (SVR), cardiac output (CO), GFR, and RPF to nonpregnant
      values. Pregnant rats received the nitric oxide synthase (NOS) inhibitor, nitro-L
      arginine methyl ester (L-NAME), orally from gestational days 7 through 14.
      Results were compared with nonpregnant and untreated pregnant rats. At 14 days
      gestation, CO significantly increased in pregnant vs. nonpregnant rats (187 +/-
      17 vs. 125 +/- 10 ml/min, P < 0.05) as SVR decreased (0.64 +/- 0.08 vs. 1.08 +/-
      0.08 mmHg. ml(-1). min, P < 0.05) and mean arterial pressure was unchanged (117
      +/- 5 vs. 125 +/- 2 mmHg, not significant). Pregnant rats also demonstrated
      increased GFR (3,015 +/- 33 vs. 2,165 +/- 136 microl/min, P < 0.01) and RPF
      (7,869 +/- 967 vs. 5,507 +/- 290 microl/min, P < 0.05) vs. nonpregnant rats. L
      NAME-treated pregnant rats had values for CO (118 +/- 7 ml/min), SVR (1.09 +/-
      0.07 mmHg. ml(-1). min), GFR (2,264 +/- 150 microl/min), and RPF (5,777 +/- 498
      microl/min), which were no different than nonpregnant animals. In summary,
      similar to human pregnancy, primary peripheral vasodilation occurs early in rat
      pregnancy. Furthermore, the hyperdynamic circulation and glomerular
      hyperfiltration of normal rat midterm pregnancy can be chronically reversed by
      NOS inhibition. These findings suggest a role for endothelial damage and
      decreased NO in the pathogenesis of preeclampsia.

PMID- 11249851
TI  - Transport asymmetry in peritoneal dialysis: application of a serial heteroporous
      peritoneal membrane model.
AB  - The transport of macromolecules during peritoneal dialysis is highly selective
      when they move from blood to dialysate but nearly completely unselective in the
      opposite direction. Aiming at describing this asymmetry, we modeled the
      peritoneal barrier as a series arrangement of two heteroporous membranes. First a
      three-pore membrane was considered, crossed by small [radius of the small pore
      (r(s)) approximately 45 A], large [radius of the large pore (r(L)) approximately
      250 A], and transcellular pores accounting for 90, 8, and 2% to the hydraulic
      conductance, respectively, and with a corresponding pore area over diffusion
      distance (A(0)/Delta x) set to 50,000 cm. We calculated the second membrane
      parameters by fitting simultaneously the bidirectional clearance of molecules
      ranging from sucrose [molecular weight = 360, permeating solute radius (a(e))
      approximately 5 A] to alpha(2)-macroglobulin (molecular weight = 820,000, a(e)
      approximately 90 A). The results describe a second two-pore membrane with very
      large pores (r(L) approximately 2,300 A) accounting for 95% of the hydraulic
      conductance, minor populations of small (r(s) approximately 67 A) and
      transcellular pores (3 and 2%, respectively), and an A(0)/Delta x approximately
      65,000 cm. The estimated peritoneal lymph flow is approximately 0.3 ml/min. The
      two membranes can be identified as the capillary endothelium and an extracellular
      interstitium lumped with the peritoneal mesothelium.

PMID- 11249852
TI  - Renal concentrating defect in mice lacking group IV cytosolic phospholipase A(2).
AB  - Eicosanoids regulate various cellular functions that are important in
      physiological and pathophysiological processes. Arachidonic acid is released from
      membranes by phospholipase A(2) (PLA(2)) activity. Activated macrophages derived
      from mice lacking the 85-kDa group IV cytosolic PLA(2) (cPLA(2)) have a markedly
      reduced release of prostaglandin E(2) and leukotrienes B(4) and C(4). Under basal
      conditions and after furosemide, urinary prostaglandin E(2) excretion is reduced
      in cPLA(2)-knockout (cPLA(2)(-/-)) mice. Serum creatinine, Na(+), K(+), and
      Ca(2+) concentrations, glomerular filtration rate, and fractional excretion of
      Na(+) and K(+) are not different in cPLA(2)(-/-) and cPLA(2)(+/+) mice. Maximal
      urinary concentration is lower in 48-h water-deprived cPLA(2)(-/-) mice compared
      with cPLA(2)(+/+) animals (1,934 +/- 324 vs. 3,541 +/- 251 mmol/kgH(2)O). Plasma
      osmolality is higher (337 +/- 5 vs. 319 +/- 3 mmol/kgH(2)O) in cPLA(2)(-/-) mice
      that lose a greater percentage of their body weight (20 +/- 2 vs. 13 +/- 1%)
      compared with cPLA(2)(+/+) mice after water deprivation. Vasopressin does not
      correct the concentrating defect. There is progressive reduction in urinary
      osmolality with age in cPLA(2)(-/-) mice. Membrane-associated aquaporin-1 (AQP1)
      expression, identified by immunocytochemical techniques, is reduced markedly in
      proximal tubules of older cPLA(2)(-/-) animals but is normal in thin descending
      limbs. However, Western blot analysis of kidney cortical samples revealed an
      equivalent AQP1 signal intensity in cPLA(2)(+/+) and cPLA(2)(-/-) animals. Young
      cPLA(2)(-/-) mice have normal proximal tubule AQP1 staining. Collecting duct
      AQP2, -3, and -4 were normally expressed in the cPLA(2)(-/-) mice. Thus mice
      lacking cPLA(2) develop an age-related defect in renal concentration that may be
      related to abnormal trafficking and/or folding of AQP1 in the proximal tubule,
      implicating cPLA(2) in these processes.

PMID- 11249854
TI  - Endothelin is a potent inhibitor of matrix metalloproteinase-2 secretion and
      activation in rat mesangial cells.
AB  - We examined the effects of endothelin (ET) on the activity of matrix
      metalloproteinase-2 (MMP-2) in cultured MCs. Addition of the ET(A) receptor
      antagonists or neutralizing anti-endothelin antibody into MC cultures markedly
      augmented the secretion and activation of MMP-2. On the contrary, addition of the
      exogenous ET-1 into MC culture significantly inhibited the synthesis of MMP-2 in
      both basal and cytokines (tumor necrosis factor-alpha and interferon-gamma) plus
      lipopolysaccharide-stimulated conditions. Furthermore, pretreatment of cells with
      exogenous ET-1 obviously prevented cytochalasin D-elicited activation of MMP-2,
      an effect that was completely abolished by ET(A) receptor antagonist, FR139317.
      In addition, ET-1 was found to be able to suppress the expression of membrane
      type-1 MMP (MT1-MMP) and promote the conversion of tissue inhibitor of matrix
      metalloproteinase-2 (TIMP-2) from cell associated form to secreted form. The
      addition of recombinant TIMP-2 into the culture abrogated dose-dependently the
      cytochalasin D-elicited activation of MMP-2. These results suggest that ET is a
      potent inhibitor of MMP-2 secretion and activation in MCs. These novel findings
      may help us understand the subtle regulation of the synthesis and activation of
      MMP-2 in MCs. It also provides us with further insight into the
      pathophysiological mechanisms involving ET in the regulation of matrix turnover
      in glomerulus.

PMID- 11249853
TI  - Altered membrane-cytoskeleton linkage and membrane blebbing in energy-depleted
      renal proximal tubular cells.
AB  - The effects of energy depletion on two membrane-cytoskeletal linker proteins
      (ezrin and myosin-1 beta) and membrane bleb formation were studied in isolated
      rabbit proximal tubule cells. Measurements of cytoskeletal-membrane interactions
      by using the laser optic trap method revealed a stronger association of control
      tubule membrane with the apical cytoskeleton compared with the basal
      cytoskeleton. Energy depletion weakened the apical membrane-cytoskeleton
      interactions to a greater degree. Biochemical studies demonstrated that energy
      depletion altered both ezrin and myosin-1 beta. The salt-insensitive ezrin
      fraction dissociated from the cytoskeleton; myosin-1beta redistributed from the
      peripheral cytoskeleton to a perinuclear/nuclear complex. These changes in ezrin
      and myosin-1 beta and the weakening of the membrane-cytoskeleton interactions
      correlated with the release of brush-border membrane blebs observed by
      differential interference contrast microscopy. Permeability of membrane blebs was
      also evaluated during energy depletion and indicated an increased
      permeabilization of basal blebs to 3-kDa dextrans. These results support the
      hypothesis that alterations in membrane-cytoskeleton linkers facilitate the
      formation and detachment of blebs by weakening membrane-cytoskeleton
      interactions.

PMID- 11249855
TI  - Two apical multidrug transporters, P-gp and MRP2, are differently altered in
      chronic renal failure.
AB  - Tubular function is altered in chronic renal failure (CRF). Whether drug
      secretion by renal tubules is modified in CRF is questioned because of frequent
      accumulation of various toxins in CRF. This function mainly involves ATP
      dependent drug transporters, particularly P-glycoprotein (P-gp) and multidrug
      resistance-associated protein (MRP) 2, both present in apical membrane of
      epithelial cells. The present study was aimed at determining the changes in P-gp
      and MRP2 expression induced by experimental CRF in kidney and liver. The
      relationship between MRP2 and glutathione metabolism changes was examined because
      MRP2 transports GSSG and glutathione conjugates. Rats underwent either 80%
      subtotal nephrectomy (Nx) or sham operation, and determinations were performed 3
      and 6 wk later. CRF induced a 70--200% rise in protein and mRNA expression of
      MRP2 after 3 and 6 wk post-Nx in remnant kidney and after 6 wk in liver. However,
      P-gp expression was unchanged by CRF. Relative to whole kidney mass, total MRP2
      levels decreased by only 27% in Nx rats whereas total P-gp levels were reduced by
      60%. Renal GSSG and total glutathione levels were increased by 30% in Nx rats,
      but glutathione-S-transferase (GST) activity was normal; liver GSSG levels and
      GST activity were reduced in Nx rats. In conclusion, CRF resulted in specific
      overexpression of MRP2 in kidney and liver. This could be an adaptative response
      to some elevated circulating toxins. The later MRP2 induction and different
      glutathione changes in liver compared with kidney suggest different mechanisms
      for MRP2 induction and/or action in these two tissues.

PMID- 11249856
TI  - A quantitative analysis of the glomerular charge barrier in the rat.
AB  - Modifying the ionic strength (I) is a gentle way to alter charge interactions,
      but it cannot be done for studies of the glomerular sieving of proteins in vivo.
      We therefore perfused 18 isolated rat kidneys with albumin solutions of different
      ionic strengths at a low temperature (cIPK) to inhibit tubular uptake and
      protease activity. Four anionic proteins were studied, namely albumin (Alb),
      orosomucoid (Oro), ovalbumin (Ova), and anionic horseradish peroxidase (aHRP),
      together with the neutral polymer Ficoll. With normal ionic strength of the
      perfusate (152 mM), the fractional clearance (theta) was 0.0018 +/- 0.0003 for
      Alb, 0.0033 +/- 0.0003 for Oro, 0.090 +/- 0.008 for Ova, and 0.062 +/- 0.002 for
      aHRP. These theta values were all lower than for Ficoll of similar hydrodynamic
      size; e.g., theta(Ficoll 36 A) was >20 times higher than theta for albumin. Low
      ionic strength (34 mM) increased size selectivity as theta for anionic proteins
      and Ficoll fell, suggesting a reduction in small-pore radius from 44 +/- 0.4 to
      41 +/- 0.5 A, P < 0.01. In contrast, low I reduced the charge density of the
      membrane, omega, to one-quarter of the 20--50 meq/l estimated at normal I. These
      dynamic changes in omega seem to be due to volume alterations of the charged gel,
      fluid shifts that easily are accounted for by the changes in electroosmotic
      pressures. The finding that low ionic strength induces inverse effects on size
      selectivity and charge density strongly suggests that separate structures of the
      glomerular wall are responsible for the two properties.

PMID- 11249857
TI  - Antisense GLUT-1 protects mesangial cells from glucose induction of GLUT-1 and
      fibronectin expression.
AB  - A stable clone of rat mesangial cells expressing antisense GLUT-1 (i.e., MCGT1AS
      cells) was developed to protect them from high glucose exposure. GLUT-1 protein
      was reduced 50%, and the 2-deoxy-[(3)H]glucose uptake rate was reduced 33% in
      MCGT1AS. MCLacZ control cells and MCGT1 GLUT-1-overexpressing cells were used for
      comparisons. In MCLacZ, 20 mM D-glucose increased GLUT-1 transcription 90% vs. no
      increase in MCGT1AS. Glucose (8 mM) and 12 mM xylitol [a hexose monophosphate
      (HMP) shunt substrate] did not stimulate GLUT-1 transcription. An 87% replacement
      of the standard 8 mM D-glucose with 3-O-methylglucose reduced GLUT-1
      transcription 80%. D-Glucose (20 mM) increased fibronectin mRNA and protein by 47
      and 100%, respectively, in MCLacZ vs. no increases in MCGT1AS. Fibronectin
      synthesis was elevated 48% in MCGT1 and reduced 44% in MCGT1AS. We conclude that
      1) transcription of GLUT-1 in response to D-glucose depends on glucose
      metabolism, although not through the HMP shunt, and 2) antisense GLUT-1 treatment
      of mesangial cells blocks D-glucose-induced GLUT-1 and fibronectin expression,
      thereby demonstrating a protective effect that could be beneficial in the setting
      of diabetes.

PMID- 11249858
TI  - Hypoxia and high glucose cause exaggerated mesangial cell growth and collagen
      synthesis: role of osteopontin.
AB  - The effect of hypoxia on the proliferation and collagen synthesis of cultured rat
      mesangial cells was examined under normal-glucose (NG, 5 mM) and high-glucose
      (HG, 25 mM)-media conditions. In addition, a role for osteopontin (OPN) in
      mediating these processes was assessed. Quiescent cultures were exposed to
      hypoxia (3% O(2)) and normoxia (18% O(2)) in a serum-free medium with NG or HG,
      and cell proliferation, collagen synthesis, and OPN expression were assessed.
      Cells exposed to hypoxia in NG medium resulted in significant increases in
      [(3)H]thymidine incorporation, cell number, and [(3)H]proline incorporation,
      respectively. HG incubations also produced significant stimulation of these
      parameters under normoxic conditions, which were markedly enhanced in cells
      exposed to hypoxia in HG medium. In addition, hypoxia and HG stimulated the mRNA
      levels of type IV collagen, and the combination of hypoxia and HG resulted in
      additive increases in type IV collagen expression. Hypoxia and HG also stimulated
      OPN mRNA and protein levels in an additive fashion. A neutralizing antibody to
      OPN or its beta(3)-integrin receptor significantly blocked the effect of hypoxia
      and HG on proliferation and collagen synthesis. In conclusion, these results
      demonstrate for the first time that hypoxia in HG medium produces exaggerated
      mesangial cell growth and type IV collagen synthesis. In addition, OPN appears to
      play a role in mediating the accelerated mesangial cell growth and collagen
      synthesis found in a hyperglycemic and hypoxic environment.

PMID- 11249859
TI  - Aldosterone induces rapid apical translocation of ENaC in early portion of renal
      collecting system: possible role of SGK.
AB  - Aldosterone controls sodium reabsorption and potassium secretion in the
      aldosterone-sensitive distal nephron (ASDN). Although clearance measurements have
      shown that aldosterone induces these transports within 30--60 min, no early
      effects have been demonstrated in vivo at the level of the apical epithelial
      sodium channel (ENaC), the main effector of this regulation. Here we show by real
      time RT-PCR and immunofluorescence that an aldosterone injection in
      adrenalectomized rats induces alpha-ENaC subunit expression along the entire ASDN
      within 2 h, whereas beta- and gamma-ENaC are constitutively expressed. In the
      proximal ASDN portions only, ENaC is shifted toward the apical cellular pole and
      the apical plasma membrane within 2 and 4 h, respectively. To address the
      question of whether the early aldosterone-induced serum and glucocorticoid
      regulated kinase (SGK) might mediate this apical shift of ENaC, we analyzed SGK
      induction in vivo. Two hours after aldosterone, SGK was highly induced in all
      segment-specific cells of the ASDN, and its level decreased thereafter. In
      Xenopus laevis oocytes, SGK induced ENaC activation and surface expression by a
      kinase activity-dependent mechanism. In conclusion, the rapid in vivo
      accumulation of SGK and alpha-ENaC after aldosterone injection takes place along
      the entire ASDN, whereas the translocation of alpha,beta,gamma-ENaC to the apical
      plasma membrane is restricted to its proximal portions. Results from oocyte
      experiments suggest the hypothesis that a localized activation of SGK may play a
      role in the mediation of ENaC translocation.

PMID- 11249860
TI  - Inflammation is probably not a prerequisite for renal interstitial fibrosis in
      normoglycemic obese rats.
AB  - We examined the role of inflammation in the development of renal interstitial
      fibrosis in Zucker obese rats, which rapidly present kidney lesions in the
      absence of hypertension and hyperglycemia. Type I and III collagens were
      quantified using a polarized light and computer-assisted image analyzer. The
      expression of mRNA encoding matrix components, adhesion molecules, chemokines,
      and growth factors was followed by RT-PCR. The presence of synthesized proteins
      as well as lymphocytes and macrophages was determined by immunohistochemistry.
      Interstitial fibrosis developed in two phases. The first phase occurred as early
      as 3 mo and resulted from a neosynthesis of type III collagen and fibronectin and
      a reduction of extracellular matrix catabolism, in parallel with an
      overexpression of transforming growth factor-beta(1) and in the absence of any
      lymphocyte or macrophage infiltration. After 6 mo, interstitial fibrosis worsened
      with a large accumulation of type I collagen, concomitantly with a large
      macrophage infiltration. Thus inflammation cannot explain the onset of
      interstitial fibrosis that developed in young, insulinoresistant, normoglycemic,
      obese Zucker rats but aggravated this process afterward.

PMID- 11249861
TI  - Glomerular laminin isoform transitions: errors in metanephric culture are
      corrected by grafting.
AB  - Glomerular basement membrane (GBM) assembly and maturation are marked by the
      replacement of laminin-1 (containing alpha 1-, beta 1-, and gamma 1-chains) with
      laminin-11 (consisting of alpha 5-, beta 2-, and gamma 1-chains). Similarly, the
      alpha 1- and alpha 2-chains of type IV collagen are replaced by collagen alpha 3
      , alpha 4-, and alpha 5(IV)-chains. The cellular origins of these molecules and
      mechanisms for isoform removal and substitution are unknown. To explore
      glomerular laminin isoform transitions in vitro, we assessed metanephric organ
      cultures. Standard culture conditions do not support endothelial cell
      differentiation, and glomerular structures that form in vitro are avascular.
      Nevertheless, extensive podocyte development occurs in these cultures, including
      the formation of foot processes and assembly of a GBM-like matrix. Here, we show
      that the podocyte-specific markers, glomerular epithelial protein 1 and nephrin,
      which are normally expressed in capillary loop stage glomeruli in vivo, are also
      expressed by glomerular figures that form in organ culture. However, the GBM-like
      segments that form in vitro do not undergo normal laminin isoform switching.
      Instead, both laminin alpha 1- and alpha 5-chains are present, as is the beta 1
      chain, but not beta 2. When avascular organ-cultured kidneys are grafted into
      anterior eye chambers, however, kidney-derived angioblasts establish extensive
      vasculature by 6 days, and glomeruli are lined by endothelial cells. We evaluated
      embryonic day 12 (E12) vascular endothelial growth factor receptor (Flk1)-lacZ
      kidneys that had first been grown in organ culture for 6--7 days and then grafted
      into wild-type mice. Correct laminin isoform substitution occurred and correlated
      with the appearance of endothelial cells expressing Flk1. Our findings indicate
      that endothelial cells, and/or factors present in the circulation, mediate normal
      GBM laminin isoform transitions in vivo.

PMID- 11249862
TI  - Upregulation of juxtaglomerular NOS1 and COX-2 precedes glomerulosclerosis in
      fawn-hooded hypertensive rats.
AB  - This study describes elevated histochemical signals for nitric oxide synthase-1
      (NOS1) and cyclooxygenase-2 (COX-2) in juxtaglomerular apparatus (JGA) and
      adjacent thick ascending limb of the kidney of fawn-hooded hypertensive rats
      (FHH). Two different age groups of FHH (8 and 16 wk; FHH8 and FHH16,
      respectively) were compared with genetically related fawn-hooded rats with normal
      blood pressure (FHL) that served as controls. Histopathological changes in FHH
      comprised focal segmental glomerulosclerosis (FSGS), focal matrix overexpression,
      and a moderate arteriolopathy with hypertrophy of the media, enhanced
      immunoreactivity for alpha-smooth muscle actin, and altered distribution of
      myofibrils. Macula densa NOS activity, as expressed by NADPH-diaphorase staining,
      and NOS1 mRNA abundance were significantly elevated in FHH8 (+153 and +88%; P <
      0.05) and FHH16 (+93 and +98%; P < 0.05), respectively. Even higher elevations
      were registered for COX-2 immunoreactivity in FHH8 (+166%; P < 0.05) and FHH16
      (+157%; P < 0.05). The intensity of renin immunoreactivity and renin mRNA
      expression in afferent arterioles was also elevated in FHH8 (+51 and +166%; P <
      0.05) and FHH16 (+105 and +136%; P < 0.05), respectively. Thus we show that
      coordinate upregulation of tubular NOS1, COX-2, and renin expression precedes,
      and continues after, the manifestation of glomerulosclerotic damage in FHH. These
      observations may have implications in understanding the role of local paracrine
      mediators in glomerular disease.

PMID- 11249863
TI  - Compensatory increase in AQP2, p-AQP2, and AQP3 expression in rats with diabetes
      mellitus.
AB  - Diabetes mellitus (DM) is associated with osmotic diuresis and natriuresis. At
      day 15, rats with DM induced by streptozotocin (n = 13) had severe hyperglycemia
      (27.1 +/- 0.4 vs. 4.7 +/- 0.1 mM in controls) and had a fivefold increase in
      water intake (123 +/- 5 vs. 25 +/- 2 ml/day) and urine output. Semiquantitative
      immunoblotting revealed a significant increase in inner medullary AQP2 (201 +/-
      12% of control rats, P < 0.05) and phosphorylated (Ser(256)) AQP2 (p-AQP2)
      abundance (299 +/- 32%) in DM rats. Also, the abundance of inner medullary AQP3
      was markedly increased to 171 +/- 19% of control levels (100 +/- 4%, n = 7, P <
      0.05). In contrast, the abundance of whole kidney AQP1 (90 +/- 3%) and inner
      medullary AQP4 (121 +/- 16%) was unchanged in rats with DM. Immunoelectron
      microscopy further revealed an increased labeling of AQP2 in the apical plasma
      membrane of collecting duct principal cells (with less labeling in the
      intracellular vesicles) of DM rats, indicating enhanced trafficking of AQP2 to
      the apical plasma membrane. There was a marked increase in urinary sodium
      excretion in DM. Only Na(+)/H(+) exchanger NHE3 was downregulated (67 +/- 10 vs.
      100 +/- 11%) whereas there were no significant changes in abundance of type 2 Na
      phosphate cotransporter (128 +/- 6 vs. 100 +/- 10%); the Na-K-2Cl cotransporter
      (125 +/- 19 vs. 100 +/- 10%); the thiazide-sensitive Na-Cl cotransporter (121 +/-
      9 vs. 100 +/- 10%); the alpha(1)-subunit of the Na-K-ATPase (106 +/- 7 vs. 100 +/
      5%); and the proximal tubule Na-HCO(3) cotransporter (98 +/- 16 vs. 100 +/- 7%).
      In conclusion, DM rats had an increased AQP2, p-AQP2, and AQP3 abundance as well
      as high AQP2 labeling of the apical plasma membrane, which is likely to represent
      a vasopressin-mediated compensatory increase in response to the severe polyuria.
      In contrast, there were no major changes in the abundance of AQP1, AQP4, and
      several major proximal and distal tubule Na(+) transporters except NHE3
      downregulation, which may participate in the increased sodium excretion.

PMID- 11249865
TI  - Tuning repolarization in the heart: a multitude of potassium channels and
      regulatory pathways.

PMID- 11249864
TI  - Post-cyclosporine-mediated hypertension and nephropathy: amelioration by vascular
      endothelial growth factor.
AB  - Recent studies have demonstrated a role for microvascular and tubulointerstitial
      injury in some models of salt-sensitive hypertension. We utilized a model of post
      cyclosporin A (CsA) nephropathy and hypertension to test the hypothesis that
      treatment with an angiogenic factor aimed at ameliorating the microvascular and
      renal injury would prevent the development of hypertension. CsA was administered
      with a low-salt diet for 45 days, resulting in a renal lesion characterized by
      afferent arteriolopathy, focal peritubular capillary loss, and tubulointerstitial
      fibrosis. Rats were then placed on a high-salt diet and randomized to receive
      either vascular endothelial growth factor (VEGF(121)) or vehicle for 14 days.
      Placement of rats with established CsA nephropathy on a high-salt diet results in
      the rapid development of salt-sensitive hypertension. VEGF(121) treatment
      resulted in lower blood pressure, and this persisted on discontinuing the VEGF.
      VEGF(121) treatment was also associated with a decrease in osteopontin
      expression, macrophage infiltration, and collagen III deposition and markedly
      stimulated resolution of the arteriolopathy (20.9 +/- 7.8 vs. 36.9 +/- 6.1%, VEGF
      vs. vehicle, P < 0.05). In conclusion, CsA-associated renal microvascular and
      tubulointerstitial injury results in the development of salt-sensitive
      hypertension. Treatment of animals with established CsA nephropathy with VEGF
      reduces the hypertensive response and accelerates histological recovery. The
      vascular protective effect of VEGF may be due to the improvement of
      arteriolopathy. Angiogenic growth factors may represent a novel strategy for
      treating CsA-associated hypertension and renal disease.

PMID- 11249866
TI  - Atherosclerosis: defeat of the defense?

PMID- 11249867
TI  - Regulation of vascular cell behavior by collagen : form is function.

PMID- 11249868
TI  - Fibrillar collagen specifically regulates human vascular smooth muscle cell genes
      involved in cellular responses and the pericellular matrix environment.
AB  - Proliferation and alpha(v)beta(3) integrin-dependent migration of vascular smooth
      muscle cells are suppressed on polymerized type I collagen. To identify genes
      specifically regulated in human smooth muscle cells by polymerized collagen, we
      used the suppressive subtraction hybridization technique. Compared with smooth
      muscle cells cultured on monomer collagen, polymerized collagen suppresses the
      following: (1) a number of other extracellular matrix proteins, including
      fibronectin, thrombospondin-1, tenascin-C, and cysteine-rich protein 61; (2)
      actin binding proteins including alpha-actinin; (3) signaling molecules; (4)
      protein synthesis-associated proteins; and (5) genes with unknown functions. Some
      of the identified genes, including cysteine-rich protein 61, show unique kinetics
      of mRNA regulation by monomer or polymerized collagen distinct from growth
      factors, suggesting extracellular matrix-specific gene modulation. Moreover, in
      vivo balloon catheter-mediated injury to the rat carotid artery induces many of
      the genes that are suppressed by polymerized collagen. Protein levels of
      thrombospondin-1 and fibronectin are also suppressed by polymerized collagen.
      Thrombospondin-1-mediated smooth muscle cell migration on vitronectin is
      significantly inhibited after culture on polymerized collagen for 24 hours, which
      is associated with decreased alpha-actinin accumulation at focal adhesions. Thus,
      polymerized type I collagen dynamically regulates gene expression, pericellular
      accumulation of extracellular matrix molecules, and the response to a given
      matrix molecule.

PMID- 11249869
TI  - Chimeric smooth muscle-specific enhancer/promoters: valuable tools for adenovirus
      mediated cardiovascular gene therapy.
AB  - Gene transfer with adenoviral vectors is an attractive approach for the treatment
      of atherosclerosis and restenosis. However, because expression of a therapeutic
      gene in nontarget tissues may have deleterious effects, artery-specific
      expression is desirable. Although expression vectors containing transcriptional
      regulatory elements of genes expressed solely in smooth muscle cells (SMCs) have
      proved efficient to restrict expression of the transgene, their use in the
      clinical setting can be limited by their reduced strength. In the present study,
      we show that low levels of transgene expression are obtained with the smooth
      muscle (SM)-specific SM22alpha promoter compared with the viral cytomegalovirus
      (CMV) enhancer/promoter. We have generated chimeric transcriptional cassettes
      containing either a SM (SM-myosin heavy chain) or a skeletal muscle (creatine
      kinase) enhancer combined with the SM22alpha promoter. With both constructs we
      observed significantly stronger expression that remains SM-specific. In vivo,
      reporter gene expression was restricted to arterial SMCs with no detectable
      signal at remote sites. Moreover, when interferon-gamma expression was driven by
      one of these two chimeras, SMC growth was inhibited as efficiently as with the
      CMV promoter. Finally, we demonstrate that neointima formation in the rat carotid
      balloon injury model was reduced to the same extent by adenoviral gene transfer
      of interferon-gamma driven either by the SM-myosin heavy chain enhancer/SM22alpha
      promoter or the CMV promoter. These results indicate that such vectors can be
      useful for the treatment of hyperproliferative vascular disorders.

PMID- 11249870
TI  - Independent regulation of cardiac Kv4.3 potassium channel expression by
      angiotensin II and phenylephrine.
AB  - Hypertrophied cardiac myocytes exhibit prolonged action potentials and decreased
      transient outward potassium current (I(to)). Because Kv4.3 is a major contributor
      to I:(to), we studied regulation of its expression in neonatal rat cardiac
      myocytes in response to the known stimulators of cardiac myocyte hypertrophy,
      angiotensin II (Ang II) and phenylephrine (PE). RNase protection assays and
      immunoblots revealed that Ang II and PE each downregulate Kv4.3 mRNA and protein.
      However, although PE induces a faster and more extensive hypertrophic response
      than Ang II, the PE effect on Kv4.3 mRNA develops slowly and is sustained,
      whereas Ang II rapidly and transiently decreases Kv4.3 mRNA expression. Turnover
      measurements revealed that Kv4.3 mRNA is very stable, with a half-life >20 hours.
      This suggests that Ang II must destabilize the channel mRNA. In contrast, PE does
      not affect the rate of Kv4.3 mRNA degradation. To test for transcriptional
      regulation, the 5' flanking region of the rat Kv4.3 gene was cloned, and Kv4.3
      promoter-reporter constructs were expressed in cardiac myocytes. Whereas Ang II
      was found to have no effect on transcription, PE inhibits Kv4.3 promoter
      activity. Pharmacological experiments also indicate that PE and Ang II act
      independently to downregulate Kv4.3 gene expression. Thus, regulation of Kv4.3
      gene expression is not a simple secondary response to hypertrophy. Rather, Ang II
      and PE use different mechanisms to decrease Kv4.3 channel expression in neonatal
      rat cardiac myocytes.

PMID- 11249871
TI  - Heterogeneity of Kv2.1 mRNA expression and delayed rectifier current in single
      isolated myocytes from rat left ventricle.
AB  - Expression of the voltage-gated K(+) channel Kv2.1, a possible molecular
      correlate for the cardiac delayed rectifier current (I(K)), has recently been
      shown to vary between individual ventricular myocytes. The functional
      consequences of this cell-to-cell heterogeneity in Kv2.1 expression are not
      known. Using multiplex single-cell reverse transcriptase-polymerase chain
      reaction (RT-PCR), we detected Kv2.1 mRNA in 47% of isolated midmyocardial
      myocytes from the rat left ventricular free wall that were positive for alpha
      myosin heavy chain mRNA (n=74). Whole-cell patch-clamp recordings demonstrated
      marked differences in the magnitude of I(K) (200 to 1450 pA at V(Pip)=40 mV)
      between individual myocytes of the same origin. Furthermore, the
      tetraethylammonium (TEA)-sensitive outward current (I(TEA)), known to be partly
      encoded by Kv2.1 in mice, revealed a wide range of current magnitudes between
      single cells (150 to 1130 pA at V(Pip)=40 mV). Combined patch-clamp recordings
      and multiplex single-cell RT-PCR analysis of the same myocytes, however, showed
      no differences in I(K) or I(TEA) magnitude or inactivation kinetics between
      myocytes expressing Kv2.1 mRNA and those that did not express Kv2.1 mRNA. In
      contrast, in all midmyocardial myocytes expressing the transient outward
      potassium current (I(to1)), Kv4 mRNA, which has been shown to underlie I(to1),
      was detected (n=10). These results indicate that I(K) heterogeneity among
      individual left ventricular myocytes cannot be explained by the distribution
      pattern of Kv2.1 mRNA. Other mechanisms besides Kv2.1 mRNA expression appear to
      determine magnitude and kinetics of I(K) in rat ventricular myocytes.

PMID- 11249872
TI  - Lipopolysaccharide internalization activates endotoxin-dependent signal
      transduction in cardiomyocytes.
AB  - We tested the hypothesis that bacterial lipopolysaccharide (LPS) must be
      internalized to facilitate endotoxin-dependent signal activation in cardiac
      myocytes. Fluorescently labeled LPS was used to treat primary cardiomyocyte
      cultures, perfused heart preparations, and the RAW264.7 macrophage cell line.
      Using confocal microscopy and spectrofluorometry, we found that LPS was rapidly
      internalized in cardiomyocyte cultures and Langendorff-perfused hearts. Although
      LPS uptake was also observed in macrophages, only a fraction of these cells were
      found to internalize endotoxin to the extent seen in cardiomyocytes.
      Colocalization experiments with organelle or structure-specific fluorophores
      showed that LPS was concentrated in the Golgi apparatus, lysosomes, and
      sarcomeres. Similar intracellular localization was demonstrated in cardiomyocytes
      by transmission electron microscopy using gold-labeled LPS. The internalization
      of LPS was dependent on endosomal trafficking, because an inhibitor of
      microfilament reorganization prevented uptake in both cardiomyocytes and whole
      hearts. Inhibition of endocytosis specifically restricted early activation of
      extracellular signal-regulated kinase proteins and nuclear factor-kappaB as well
      as later tumor necrosis factor-alpha production and inducible nitric oxide
      synthase expression. In conclusion, we have demonstrated that bacterial endotoxin
      is internalized and transported to specific intracellular sites in heart cells
      and that these events are obligatory for activation of LPS-dependent signal
      transduction.

PMID- 11249873
TI  - NAD(P)H oxidase-derived superoxide mediates hypercholesterolemia-induced
      leukocyte-endothelial cell adhesion.
AB  - Experimental animals placed on a high-cholesterol diet for 2 or more weeks
      exhibit an inflammatory response in postcapillary venules. The aims of this study
      were to determine (1) whether superoxide mediates the hypercholesterolemia
      induced inflammatory response and (2) whether leukocyte and/or vessel wall
      NAD(P)H oxidase contributes to this response. Intravital videomicroscopy was used
      to quantify leukocyte-endothelial cell adhesion in cremasteric postcapillary
      venules of wild-type (WT) mice, CuZn-superoxide dismutase transgenic (SOD TgN)
      mice, and mice heterozygous (p47(phox)+/-) or homozygous (p47(phox)-/-) for
      NAD(P)H oxidase placed on either a normal diet or high-cholesterol diet (HCD) for
      2 weeks. The number of adherent and emigrated leukocytes in postcapillary venules
      of WT HCD mice was significantly higher than that detected in venules of their
      normal-diet counterparts. However, the HCD-induced recruitment of adherent and
      emigrated leukocytes was not observed in SOD TgN mice. Whereas
      hypercholesterolemic p47(phox)+/- and WT mice exhibited similar inflammatory
      responses, p47(phox)-/- mice did not. Bone marrow chimeras were developed to
      selectively delete p47(phox) from either the vessel wall or circulating
      leukocytes. Whereas WT marrow transplanted into WT mice produced a normal
      inflammatory response of venules to HCD, chimeric mice with p47(phox) deficiency
      in either the vessel wall or leukocytes exhibited an attenuated inflammatory
      response to HCD that was comparable with that observed in p47(phox)-/- HCD mice.
      Our findings indicate that enhanced superoxide production is a critical event
      that initiates the leukocyte-endothelial cell adhesion in postcapillary venules
      of HCD mice. NAD(P)H oxidase appears to be an important source of this
      superoxide.

PMID- 11249874
TI  - Heme oxygenase-1 inhibits atherosclerotic lesion formation in ldl-receptor
      knockout mice.
AB  - Heme oxygenase-1 (HO-1) is induced by a variety of conditions associated with
      oxidative stress. We demonstrated that mildly oxidized LDL markedly induces HO-1
      in human aortic endothelial and smooth muscle cell cocultures and that its
      induction results in the attenuation of monocyte chemotaxis resulting from
      treatment with mildly oxidized LDL in vitro. To elucidate the role of HO-1 in the
      development of atherosclerotic lesions in vivo, we modulated HO-1 expression in
      LDL-receptor knockout mice fed high-fat diets. During 6-week high-fat diet
      trials, intraperitoneal injections of hemin (H group) or hemin and
      desferrioxamine (HD group) to induce HO-1, Sn-protoporphyrin IX to inhibit HO-1
      (Sn group), and saline as control (C group) were performed. Both the H and HD
      groups showed significantly less mean atherosclerotic lesions in the proximal
      aorta compared with the C group, whereas the Sn group showed larger lesion
      compared with the C group. Modulation of HO expression and HO activities were
      confirmed by Northern blot analysis and HO activity assay. Immunohistochemical
      studies revealed significant HO-1 expression in atherosclerotic lesions, where
      oxidized phospholipids also localized. Major cell types expressing HO-1 were
      macrophages and foam cells in the lesions. HO modulations affected plasma lipid
      hydroperoxide (LPO) levels and nitrite/nitrate levels. These results suggest that
      HO-1, induced under hyperlipidemia, functioned as an intrinsic protective factor
      against atherosclerotic lesion formation, possibly by inhibiting lipid
      peroxidation and influencing the nitric oxide pathway.

PMID- 11249875
TI  - No-flow ischemia inhibits insulin signaling in heart by decreasing intracellular
      pH.
AB  - Glucose-insulin-potassium solutions exert beneficial effects on the ischemic
      heart by reducing infarct size and mortality and improving postischemic left
      ventricular function. Insulin could be the critical protective component of this
      mixture, although the insulin response of the ischemic and postischemic
      myocardium has not been systematically investigated. The aim of this work was to
      study the insulin response during ischemia by analyzing insulin signaling. This
      was evaluated by measuring changes in activity and/or phosphorylation state of
      insulin signaling elements in isolated perfused rat hearts submitted to no-flow
      ischemia. Intracellular pH (pH(i)) was measured by NMR. No-flow ischemia
      antagonized insulin signaling including insulin receptor, insulin receptor
      substrate-1, phosphatidylinositol 3-kinase, protein kinase B, p70 ribosomal S6
      kinase, and glycogen synthase kinase-3. These changes were concomitant with
      intracellular acidosis. Perfusing hearts with ouabain and amiloride in normoxic
      conditions decreased pH(i) and insulin signaling, whereas perfusing at pH 8.2
      counteracted the drop in pH(i) and the inhibition of insulin signaling by
      ischemia. Incubation of cardiomyocytes in normoxic conditions, but at pH values
      below 6.75, mimicked the effect of ischemia and also inhibited insulin-stimulated
      glucose uptake. Finally, the in vitro insulin receptor tyrosine kinase activity
      was progressively inhibited at pH values below physiological pH(i), being
      abolished at pH 6.0. Therefore, ischemic acidosis decreases kinase activity and
      tyrosine phosphorylation of the insulin receptor thereby preventing activation of
      the downstream components of the signaling pathway. We conclude that severe
      ischemia inhibits insulin signaling by decreasing pH(i).

PMID- 11249876
TI  - A(1) or A(3) adenosine receptors induce late preconditioning against infarction
      in conscious rabbits by different mechanisms.
AB  - We investigated whether activation of A(1) or A(3) adenosine receptors (ARs)
      induces late preconditioning (PC) against infarction in conscious rabbits using
      the selective AR agonists 2-chloro-N(6)-cyclopentyladenosine (CCPA) and N(6)-3
      iodobenzyladenosine-5'-N-methylcarboxamide (IB-MECA). In vitro radioligand
      binding and cAMP assays demonstrated CCPA to be approximately 200- to 400-fold
      selective for the rabbit A(1)AR and IB-MECA to be approximately 20-fold selective
      for the rabbit A(3)AR. We observed that (1) pretreatment of rabbits 24 hours
      earlier with CCPA (100 microgram/kg IV bolus) or IB-MECA (100 or 300
      microgram/kg) resulted in an approximately 35% to 40% reduction in the size of
      the infarct induced by 30 minutes of coronary artery occlusion and 72 hours of
      reperfusion compared with vehicle-treated rabbits, whereas pretreatment with the
      selective A(2A)AR agonist CGS 21680 (100 microgram/kg) had no effect; (2) the
      delayed cardioprotective effect of CCPA, but not that of IB-MECA, was completely
      blocked by coadministration of the highly selective A(1)AR antagonist N-0861; (3)
      inhibition of nitric oxide synthase (NOS) with N(omega)-nitro-L-arginine during
      the 30-minute occlusion abrogated the infarct-sparing action of CCPA but not that
      of IB-MECA; and (4) inhibition of ATP-sensitive potassium (K(ATP)) channels with
      sodium 5-hydroxydecanoate during the 30-minute occlusion blocked the
      cardioprotective effects of both CCPA and IB-MECA. Taken together, these results
      indicate that activation of either A(1)ARs or A(3)ARs (but not A(2A)ARs) elicits
      delayed protection against infarction in conscious rabbits and that both A(1)AR-
      and A(3)AR-induced cardioprotection involves opening of K(ATP) channels. However,
      A(1)AR-induced late PC uses an NOS-dependent pathway whereas A(3)AR-induced late
      PC is mediated by an NOS-independent pathway.

PMID- 11249877
TI  - Mitochondrial DNA damage and dysfunction associated with oxidative stress in
      failing hearts after myocardial infarction.
AB  - Mitochondria are one of the enzymatic sources of reactive oxygen species (ROS)
      and could also be a major target for ROS-mediated damage. We hypothesized that
      ROS may induce mitochondrial DNA (mtDNA) damage, which leads to defects of mtDNA
      encoded gene expression and respiratory chain complex enzymes and thus may
      contribute to the progression of left ventricular (LV) remodeling and failure
      after myocardial infarction (MI). In a murine model of MI and remodeling created
      by the left anterior descending coronary artery ligation for 4 weeks, the LV was
      dilated and contractility was diminished. Hydroxyl radicals, which originated
      from the superoxide anion, and lipid peroxide formation in the mitochondria were
      both increased in the noninfarcted LV from MI mice. The mtDNA copy number
      relative to the nuclear gene (18S rRNA) preferentially decreased by 44% in MI by
      a Southern blot analysis, associated with a parallel decrease (30% to 50% of
      sham) in the mtDNA-encoded gene transcripts, including the subunits of complex I
      (ND1, 2, 3, 4, 4L, and 5), complex III (cytochrome b), complex IV (cytochrome c
      oxidase), and rRNA (12S and 16S). Consistent with these molecular changes, the
      enzymatic activity of complexes I, III, and IV decreased in MI, whereas, in
      contrast, complex II and citrate synthase, encoded only by nuclear DNA, both
      remained at normal levels. An intimate link among ROS, mtDNA damage, and defects
      in the electron transport function, which may lead to an additional generation of
      ROS, might play an important role in the development and progression of LV
      remodeling and failure.

PMID- 11249879
TI  - Upregulation of the nitric oxide-cGMP pathway in aged myocardium.

PMID- 11249878
TI  - I(f) current and spontaneous activity in mouse embryonic ventricular myocytes.
AB  - Knowledge of the initiation of electrical and contractile activity in the
      embryonic heart relies to a large extent on data obtained in chicken. In recent
      years, molecular biological techniques have raised an interest in mouse
      physiology, including early embryonic development. We studied action potentials
      and the occurrence of one of the pacemaker currents, I(f), by the whole-cell
      voltage and current-clamp technique at the earliest stage at which a regular
      heartbeat is established (9.5 days postcoitum) and at 1 day before birth. We
      show, first, that at the early stage there is a prominent I(f) in mouse embryonic
      ventricles, which decreases by 82% before birth in concert with the loss of
      regular spontaneous activity of ventricular cells. Second, the decrease in I(f)
      current is associated with a slight change in channel gating kinetics and a
      decrease in total mRNA expression of the genes encoding for I(f) current. Third,
      the most prevalent mRNA subtype is switched from HCN4 to HCN2 during the second
      half of embryonic development. Fourth, the I(f) current may be modulated by the
      beta-adrenergic cascade, although the coupling to the beta-adrenoceptor in the
      sarcolemma itself is not yet mature. We conclude that I(f) current of the sinus
      node type is present in early embryonic mouse ventricular cells. In association
      with a loss of I(f) current, the ventricle tends to lose pacemaker potency during
      the second half of embryonic development.

PMID- 11249880
TI  - The distribution of refractory periods influences the dynamics of ventricular
      fibrillation.
AB  - The spatial and dynamic properties of ventricular fibrillation (VF) may be random
      or related to cellular electrical properties of the normal heart. Local
      activation intervals (AIs) in VF may depend on the local refractory period (RP),
      and sustained VF may require a steep action potential (AP) restitution curve. In
      guinea pig hearts, AP durations (APDs) and RPs on the epicardium are shorter at
      the apex and progressively longer toward the base, producing gradients of RPs
      that may influence the spatial organization of VF. In the present study, the
      influence of APDs on VF dynamics is investigated in perfused guinea pig hearts
      stained with a voltage-sensitive dye by comparing APD gradients to the dynamics
      of VF elicited by burst pacing. In VF, AIs had no clear periodicity, but average
      AIs were shorter at the apex (57.5+/-8.1 ms) than the base (76.1+/-1.5 ms, n=6,
      P<0.05) and had gradients similar to APD gradients (correlation coefficient
      0.71+/-0.04). Analysis of local velocity vectors showed no preferential
      directions, and fast Fourier transform (FFT) power spectra were broad (10 to 24
      Hz) with multiple peaks (n=6). However, the selective inhibition of delayed K(+)
      rectifying currents, I(Kr) (E4031; 0.5 micromol/L, n=3), shifted FFT spectra from
      complex to a lower dominant frequency (10 Hz) and altered repolarization but
      retained the correlation between mean AIs and RPs. Thus, VF dynamics are
      consistent with a multiple wave-make and wave-break mechanism, and the local RP
      influences VF dynamics by limiting the range of VF frequencies and AIs at each
      site. The full text of this article is available at http://www.circresaha.org.

PMID- 11249881
TI  - The use of hyperoxia to induce chronic mild oxidative stress in RPE cells in
      vitro.
AB  - PURPOSE: To establish a model of mild and chronic oxidative stress using
      hyperoxia for retinal pigment epithelial (RPE) cells in vitro. METHODS: RPE340
      cells and WI38 lung fibroblasts were grown in normal oxygen (20% O2) and
      hyperoxia (40% O2 or 60% O2). After cell viability was examined, the levels of
      reactive oxygen intermediates (ROI) by flow cytometry and heme oxygenase-1 (HO-1)
      mRNA by northern analysis were measured as markers of oxidative stress in both
      cell types. Proliferative ability and gene expression pattern of growth factors
      were studied to demonstrate the phenotypic changes induced by mild oxidative
      stress upon these cells. RESULTS: While decreased by 60% O2, 40% O2 did not
      affect viability in both cell types, ROI production and HO-1 mRNA expression were
      elevated in hyperoxia compared to controls, but were inhibited with the
      antioxidant dehydro-ascorbic acid (DHA). The proliferation of cells by hyperoxia
      was inhibited in both cell types. The expression of growth factors induced by
      hyperoxia was cell type dependent. Fibroblast growth factor-2 mRNA was unchanged
      in RPE cells, but was increased in fibroblasts. Transforming growth factor-beta2
      was decreased in RPE cells, but unchanged in fibroblasts. Vascular endothelial
      growth factor was downregulated in RPE cells, while upregulated in fibroblasts.
      Connective tissue growth factor was decreased in RPE cells, but was unchanged in
      fibroblasts. CONCLUSIONS: The results demonstrate that hyperoxia induces mild
      oxidative stress which alters the phenotype of cells in a cell type specific
      manner.

PMID- 11249882
TI  - Determinants and prognostic information provided by pulse pressure in patients
      with coronary artery disease undergoing revascularization. The Balloon
      Angioplasty Revascularization Investigation (BARI).
AB  - Arterial stiffness, as evidenced by increased pulse pressure (PP), is associated
      with adverse cardiovascular events. However, the prognostic importance of PP in
      patients who have undergone revascularization is unknown. We examined the
      prognostic importance of PP and predictors of increased PP in patients entered
      into the Balloon Angioplasty Revascularization Investigation (BARI). Estimated
      correlation and standardized regression coefficients were reported, indicating
      the relative magnitude of independent effects of baseline characteristics on PP.
      The independent association of PP and outcome over 5 years was determined.
      Baseline characteristics independently associated with PP were higher mean
      arterial pressure, older age, female sex, noncoronary vascular disease, history
      of diabetes mellitus, and history of hypertension (p <0.001 for all). Cox
      regression covariates significantly associated with time to death were age,
      smoking, male gender, diabetes history, congestive heart failure, and baseline
      use of angiotensin-converting enzyme inhibitors, diuretic, or digitalis. When PP
      was added to the model, it was found to be an independent predictor of time to
      death (p = 0.008). When PP and mean arterial pressure were added to the model, PP
      remained significantly associated with time to death (p = 0.033). When renal
      disease and noncoronary vascular disease were added to the model, the relative
      risk declined from 1.07 to 1.04 and the association was no longer statistically
      significant. Thus, increased PP is directly and independently associated with
      mean arterial pressure, hypertension, age > or =65 years, diabetes mellitus, and
      the presence of noncoronary vascular disease, and inversely associated with a
      history of myocardial infarction. After coronary revascularization, PP,
      reflecting arterial stiffness, is independently associated with total mortality.

PMID- 11249883
TI  - Comparison of immediate and one-year outcome after coronary angioplasty of
      narrowing < 3 mm with those > or =3 mm ( the National Heart, Lung, and Blood
      Institute Dynamic Registry).
AB  - Balloon angioplasty of small coronary artery lesions has been associated with
      lower success and higher complication rates than large coronary artery lesions.
      This study evaluates the in-hospital and 1-year outcome of the treatment of small
      coronary artery lesions in the modern era of interventional cardiology and
      compares it with the outcome of treating large coronary artery lesions. Of 1,658
      patients with a single lesion treated from July 1997 to February 1998 in the
      National Heart, Lung, and Blood Institute (NHLBI) Dynamic Registry, there were
      587 patients with small coronary artery lesions (<3 mm) and 1,071 patients with
      large coronary artery lesions (> or =3 mm). Success, in-hospital, and 1-year
      outcomes between both groups were compared. Patients with lesions in small
      coronary arteries were more often women, insulin-treated diabetics, and had
      undergone more prior coronary bypass graft surgery. Conventional angioplasty
      alone was performed more often and angioplasty with stents was performed less
      often in the small coronary artery than in the large coronary artery group.
      Angiographic success was slightly lower in the small coronary artery group (94.2%
      vs 96.9%, p <0.05). Periprocedural and in-hospital complication rates were
      similar in both groups. Likewise, at 1-year follow-up, major adverse cardiac
      events including death, myocardial infarction, and coronary artery bypass graft
      surgery were relatively low and comparable between the 2 groups, although
      patients with small coronary arteries were more likely to undergo repeat
      revascularization (17.4% vs 13.6%, p <0.05). Treatment of lesions in small
      coronary arteries in the modern era is associated with high success and low
      complication rates, comparable to the treatment of large coronary artery lesions,
      although the incidence of repeat revascularization was significantly greater at
      follow-up even if stents were used.

PMID- 11249884
TI  - Optimal time for predicting myocardial viability after successful primary
      angioplasty in acute myocardial infarction: a study using myocardial contrast
      echocardiography.
AB  - This study sought to elucidate serial changes in microvascular integrity during
      papaverine-induced hyperemia in the risk area for myocardial infarction. In
      addition, we attempted to determine the optimal time for predicting myocardial
      viability. Seventy-two patients who underwent serial myocardial contrast
      echocardiography (MCE) before and shortly after (day 1), 1 day (day 2), and 3
      weeks (day 21) after recanalization were studied. In 18 of 72 patients, MCE was
      performed at baseline and during hyperemia using selective intracoronary infusion
      of papaverine. Both the peak grayscale ratio (PGSR) within the risk area, and the
      no- and low-reflow ratio (LR ratio) were analyzed in each stage. Left ventricular
      regional wall motion (RWM) was determined 6 months after recanalization. The
      correlation coefficient between PGSR with papaverine on day 1 and that on day 2
      was 0.54 (p = 0.02); it was 0.50 (p = 0.04) between day 1 and day 21, and 0.82 (p
      = 0.001) between day 2 and day 21. On day 1, the correlation coefficient between
      the LR ratio with papaverine and RWM was 0.60 (p = 0.02), which changed to 0.72
      (p = 0.003) on day 2 and 0.54 (p = 0.04) on day 21, respectively. The best time
      to predict viable myocardium was established on day 2 by receiver operating
      characteristics curves. ST-segment re-elevation, elapsed time from onset to
      recanalization, and antecedent angina pectoris were independent factors for PGSR
      on day 2 using stepwise and multiple linear regression analysis. This study
      suggests that the optimal time to estimate microvascular integrity for predicting
      myocardial viability might be 1 day after recanalization, which is neither
      shortly after recanalization nor during the convalescent stage.

PMID- 11249885
TI  - Comparison of direct coronary stenting with and without balloon predilatation in
      patients with stable angina pectoris. BET (Benefit Evaluation of Direct Coronary
      Stenting) Study Group.
AB  - The purpose of this study was to compare the effects of stent placement with and
      without balloon predilatation on duration of the procedure, reduction of
      procedure-related costs, and clinical outcomes. Although preliminary trials of
      direct coronary stenting have demonstrated promising results, the lack of
      randomized studies with long-term follow-up has limited the critical evaluation
      of the role of direct stenting in the treatment of obstructive coronary artery
      disease. Between January and September 1999, 338 patients were randomly assigned
      to either direct stent implantation (DS+; 173 patients) or standard stent
      implantation with balloon predilatation (DS-; 165 patients). Baseline clinical
      and angiographic characteristics were similar in the 2 groups. Procedural success
      was achieved in 98.3% of patients assigned to DS+ and 97.5% of patients assigned
      to DS- (p = NS), with a crossover rate of 13.9%. Compared with DS-, DS+ conferred
      a dramatic reduction in procedure-related cost ($956.4 +/- $352.2 vs $1,164.6 +/-
      $383.9, p <0.0001) and duration of the procedure (424.2 +/- 412.1 vs 634.5 +/-
      390.1 seconds, p < 0.0001). At 6-month follow-up, the incidence of major adverse
      cardiac events including death, angina pectoris, myocardial infarction,
      congestive heart failure, repeat angioplasty, or coronary artery bypass graft
      surgery was 5.3% in DS+ and 11.4% in DS- (p = NS). Multivariate analysis
      demonstrated that major adverse cardiac events rates were related to stent length
      of 10 mm (relative risk [RR] 3.25, 95% confidence intervals [CI] 1.36 to 7.78; p
      = 0.008), stent diameter of 3 mm (RR 2.69, 95% CI 1.03 to 7.06; p = 0.043), and
      complex lesion type C (RR 2.83, 95% CI 1.02 to 7.85; p = 0.045). Thus, in
      selected patients, this prospective randomized study shows the feasibility of DS+
      with reduction in procedural cost and length, and without an increase in in
      hospital clinical events and major adverse cardiac events at 6-month follow-up.

PMID- 11249887
TI  - A propensity analysis of cigarette smoking and mortality with consideration of
      the effects of alcohol.
AB  - Although it is well established that cigarette smoking causes excess mortality,
      the extent of the increased risk has been challenged because self-selection
      biases and confounding factors may not have been adequately accounted for in
      prior studies. We therefore performed a propensity analysis on a population-based
      cohort. A logistic regression model was used to generate a propensity score for
      current smoking in 6,099 adults (mean age 46 years, 54% men, 36% current smokers)
      participating in the National Heart Lung and Blood Institute's (NHLBI) Lipid
      Research Clinic Prevalence Study. During 12 years of follow-up, 513 subjects (8%)
      died. After adjusting for age, current smoking was strongly associated with death
      (compared with never and former smokers, relative risk [RR] 2.69, 95% confidence
      interval [CI] 1.98 to 0.64, p <0.0001 and RR 1.79, 95% CI 1.26 to 2.55, p =
      0.001, respectively). After adjusting for a propensity score based on 27
      covariates and the covariates themselves, current smoking remained strongly and
      independently predictive of excessive death risk in smokers compared with never
      and former smokers (adjusted RR 2.96, 95% CI 2.16 to 4.05, p <0.0001 and adjusted
      RR 1.87, 95% CI 1.31 to 2.67, p = 0.0006, respectively). Although smokers were
      more likely to also drink alcohol, an interaction was noted, whereby, after
      adjustment for propensity score and other covariates, current smoking was
      associated with a moderately strong increase in mortality among drinkers
      (adjusted RR 2.00, 95% CI 1.42 to 2.82, p <0.0001), but was also associated with
      a markedly increased death risk among nondrinkers (adjusted RR 4.74, 95% CI 3.24
      to 6.92, p <0.0001). The independent association of smoking with death even after
      a rigorous propensity analysis argues that it is highly unlikely that the link
      between smoking and mortality is materially biased or confounded.

PMID- 11249886
TI  - Results of the study to determine rotablator and transluminal angioplasty
      strategy (STRATAS).
AB  - Rotational atherectomy is used to debulk calcified or complex coronary stenoses.
      Whether aggressive burr sizing with minimal balloon dilation (<1 atm) to limit
      deep wall arterial injury improves results is unknown. Patients being considered
      for elective rotational atherectomy were randomized to either an "aggressive"
      strategy (n = 249) (maximum burr/artery >0.70 alone, or with adjunctive balloon
      inflation < or = 1 atm), or a "routine" strategy (n = 248) (maximum burr/artery <
      or =0.70 and routine balloon inflation > or =4 atm). Patient age was 62 +/- 11
      years. Fifty-nine percent routine and 60% aggressive strategy patients had class
      III to IV angina. Fifteen percent routine and 16% aggressive strategy patients
      had a restenotic lesion treated; lesion length was 13.6 versus 13.7 mm. Reference
      vessel diameter was 2.64 mm. Maximum burr size (1.8 vs 2.1 mm), burr/artery ratio
      (0.71 vs 0.82), and number of burrs used (1.9 vs 2.7) were greater for the
      aggressive strategy, p <0.0001. Final minimum lumen diameter and residual
      stenosis were 1.97 mm and 26% for the routine strategy versus 1.95 mm and 27% for
      the aggressive strategy. Clinical success was 93.5% for the routine strategy and
      93.9% for the aggressive strategy. Creatine kinase-myocardial band (CK-MB) was >5
      times normal in 7% of the routine versus 11% of the aggressive group. CK-MB
      elevation was associated with a decrease in rpm of >5,000 from baseline for a
      cumulative time >5 seconds, p = 0.002. At 6 months, 22% of the routine patients
      versus 31% of the aggressive strategy patients had target lesion
      revascularization. Angiographic follow-up (77%) showed minimum lumen diameter to
      be 1.26 mm in the routine group versus 1.16 mm in the aggressive group, and the
      loss index 0.54 versus 0.62. Dichotomous restenosis was 52% for the routine
      strategy versus 58% for the aggressive strategy. Multivariable analysis indicated
      that left anterior descending location (odds ratio 1.67, p = 0.02) and operator
      reported excessive speed decrease >5,000 rpm (odds ratio 1.74, p = 0.01) were
      significantly associated with restenosis. Thus, the aggressive rotational
      atherectomy strategy offers no advantage over more routine burr sizing plus
      routine angioplasty. Operator technique reflected by an rpm decrease of >5,000
      from baseline is associated with CK-MB elevation and restenosis.

PMID- 11249888
TI  - Exercise performance and training in patients with implantable cardioverter
      defibrillators and coronary heart disease.
AB  - The aim of this preliminary study was to compare exercise performance and the
      effect of exercise training in cardiac patients with and without an implantable
      cardioverter-defibrillator (ICD). There are few data on exercise performance and
      on the effect of exercise training in patients with an ICD. Data in patients with
      an ICD (n = 8) were compared with those from a matched control group (n = 16).
      Patients performed maximal cycle-ergometer testing before and after 3 months of
      exercise training. All patients had to stop the exercise test for reasons of
      exhaustion. The predetermined heart rate threshold in ICD patients, set at the
      detection rate of the ICD minus 30 beats/min, was not reached. Before training,
      peak oxygen uptake was not different in the ICD patients compared with the
      control group (21.0 +/- 6.9 vs 21.9 +/- 5.0 ml oxygen standard temperature
      pressure dry/min/kg). Exercise training increased peak oxygen uptake to a similar
      extent in both groups, 20% and 24%, respectively. One ICD patient developed
      uneventful ventricular tachycardia at the end of the post-training exercise test,
      and another during training. Thus, exercise performance and the favorable
      response to a 3-month exercise training program are comparable in patients with
      ICD and matched control patients. However, tachyarrhythmias may occur during
      exercise testing or training and require special attention. Selected patients
      with ICD can be encouraged to participate in medically supervised exercise
      training programs. The results of this study should be confirmed with additional
      studies on larger numbers of subjects.

PMID- 11249889
TI  - Electrophysiologic and clinical effects of angiotensin-converting enzyme
      inhibitors in patients with prior myocardial infarction, nonsustained ventricular
      tachycardia, and depressed left ventricular function. MUSTT Investigators.
      Multicenter UnSustained Tachycardia Trial.
AB  - Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce sudden
      cardiac death and all-cause mortality. They also may have direct antiarrhythmic
      properties. We retrospectively analyzed the data from the Multicenter UnSustained
      Tachycardia Trial (MUSTT), to determine the effects of ACE inhibitors on
      inducibility of sustained ventricular tachycardia and on sudden cardiac death and
      overall mortality in 2,087 patients with prior myocardial infarction,
      nonsustained ventricular tachycardia, and depressed left ventricular function.
      Results of electrophysiologic testing were compared by use of ACE inhibitors at
      baseline, and outcomes were compared between the 564 patients prescribed ACE
      inhibitors at discharge and the 1,523 patients who did not receive treatment. The
      inducibility of sustained ventricular tachycardia during electrophysiologic
      testing did not differ by baseline ACE inhibitor use (unadjusted p = 0.75).
      Patients discharged from hospital on ACE inhibitors had a lower ejection
      fraction, more extensive coronary artery disease, and fewer previous
      revascularizations at baseline. After adjustments for differences in baseline
      factors and initial hospitalization variables, there were no significant
      differences in total mortality (p = 0.47) or arrhythmic death or cardiac arrest
      (p = 0.51) with ACE inhibitor use at discharge over a median 43 months of follow
      up.

PMID- 11249890
TI  - Efficacy and safety of losartan/hydrochlorothiazide in patients with severe
      hypertension.
AB  - This 12-week, open-label, multicenter study assessed the efficacy and safety of
      losartan/hydrochlorothiazide (HCTZ), alone or in combination with other
      antihypertensive agents, in the treatment of patients with severe systemic
      hypertension. Treatment began with once-daily losartan/HCTZ 50/12.5 mg. The dose
      was increased to 100/25 mg, if required, to achieve blood pressure (BP) control
      (sitting diastolic BP <95 mm Hg); felodipine (extended release) and/or atenolol
      could be added if target sitting diastolic BP was not achieved with losartan/HCTZ
      alone. Mean sitting systolic BP of the 131 patients enrolled was 165.3 mm Hg at
      baseline and 139.8 mm Hg at final visit (reduction -25.4 mm Hg; p < or =0.01).
      Mean sitting diastolic BP was 111.9 mm Hg at baseline and 93.6 mm Hg at final
      visit (reduction -18.4 mm Hg; p < or =0.01). After 2 weeks of treatment, 63.8% of
      patients (83 of 130) were taking losartan/HCTZ 50/12.5 mg alone. By the final
      visit, one third of patients (35.1%; 46/131) were still only taking
      losartan/HCTZ. Most patients (48.1%; 63 of 131) were taking losartan/HCTZ 100/25
      mg plus felodipine (extended release) at the final visit. Losartan/HCTZ was well
      tolerated. Drug-related adverse experiences occurred in 30 patients (22.9%). Only
      2 patients (1.5%) had a serious adverse experience; 6 patients (4.6%)
      discontinued the drug because of an adverse experience. In conclusion, losartan/
      HCTZ, alone or as part of a regimen with other standard antihypertensive agents,
      is effective and well tolerated in the treatment of patients with severe
      hypertension.

PMID- 11249892
TI  - Ventricular and myocardial function following treatment of hypertension.
AB  - This study assesses and evaluates left ventricular (LV) contractile function
      after treatment of hypertension, with an emphasis on LV midwall mechanics.
      Although prior studies have assessed cardiac function after hypertension
      treatment, none has performed an analysis of LV midwall mechanics. The Veterans
      Affairs Study of monotherapy in hypertension was a study large enough to permit
      analysis of midwall mechanics across a wide spectrum of mass changes accompanying
      hypertension treatment. LV chamber function was assessed by computing fractional
      shortening at the endocardial surface; LV midwall shortening was used to define
      myocardial function. Both shortening indexes were related to end-systolic
      circumferential stress in the entire population by partitioning values of mass
      and relative wall thickness changes. Two hundred sixty-eight patients were
      studied at baseline and again after a 1- or 2-year period. In the entire group,
      there was no significant change in circumferential shortening either at the
      endocardium (38 +/- 8% at baseline vs 37 +/- 7% at follow up, p = 0.29) or in
      shortening at the midwall (20 +/- 3% vs 20 +/- 3%, p = 0.53). However, 83
      patients had a reduction in relative wall thickness and an increase in midwall
      shortening. The change in midwall shortening was significantly related to changes
      in relative wall thickness (r = -0.53, p = 0.0001). Thus, reductions in LV mass
      associated with antihypertensive therapy are generally not accompanied by a
      decrement in LV chamber or myocardial function. Improvement in midwall shortening
      is more closely related to normalization of LV geometry than to reduction in LV
      mass.

PMID- 11249891
TI  - Comparative effects of candesartan cilexetil and amlodipine in patients with mild
      systemic hypertension. Comparison of Candesartan and Amlodipine for Safety,
      Tolerability and Efficacy (CASTLE) Study Investigators.
AB  - The comparative antihypertensive efficacy and tolerability of the angiotensin II
      receptor blocker candesartan cilexetil and the calcium channel blocker amlodipine
      were evaluated in an 8-week, multicenter, double-blind, randomized, parallel
      group, forced-titration study in 251 adult patients (45% women, 16% black) with
      mild hypertension (stage 1). Following a 4- to 5-week placebo run-in period,
      patients with sitting diastolic blood pressure (BP) of 90 to 99 mm Hg received
      candesartan cilexetil 16 mg (n = 123) or amlodipine 5 mg (n = 128) once daily.
      After 4 weeks of double-blind treatment, patients were uptitrated to candesartan
      cilexetil 32 mg or amlodipine 10 mg once daily. There were no significant
      differences between the candesartan cilexetil and amlodipine regimens for
      reducing BP; mean systolic BP/diastolic BP reductions were -15.2/-10.2 mm Hg
      versus -15.4/-11.3 mm Hg, respectively (p = 0.88/0.25). Overall, 79% of patients
      on candesartan cilexetil and 87% of those on amlodipine were controlled
      (diastolic BP <90 mm Hg). A total of 3.3% of patients on candesartan cilexetil
      discontinued treatment, compared with 9.4% of patients on amlodipine, including
      2.4% versus 4.7% for adverse events and 0% versus 1.6% for peripheral edema,
      respectively. Peripheral edema, the prespecified primary tolerability end point,
      occurred with significantly greater frequency in patients on amlodipine (22.1%;
      mild 8.7%, moderate 11.8%, severe 1.6%) versus patients on candesartan cilexetil
      (8.9%; mild 8.1%, moderate 0.8%) (p = 0.005). Candesartan cilexetil and
      amlodipine are both highly effective in controlling BP in patients with mild
      hypertension. Candesartan cilexetil offers a significant tolerability advantage
      with respect to less risk of developing peripheral edema.

PMID- 11249894
TI  - Impaired retention of technetium-99m tetrofosmin in hypertrophic cardiomyopathy.
AB  - The purpose of this study was to determine whether myocardial imaging using
      technetium-99m tetrofosmin can noninvasively identify myocardial damage in
      hypertrophic cardiomyopathy (HC). The study consisted of 10 patients with apical
      HC, 10 with asymmetric septal HC (ASH) group, 5 with dilated cardiomyopathy (DC)
      like group, and 20 healthy subjects. With use of a bull's-eye map of single
      photon emission computed tomographic imaging, the total defect score of
      tetrofosmin and the washout rate were assessed in 5 segments (septum, and
      anterior, lateral, and inferior walls, and apex) of the left ventricle. A
      localized increase in defect score and washout rate was observed in the
      hypertrophied region in the group with apical HC. An increased washout rate was
      observed in the ASH group regardless of hypertrophy, suggesting that tetrofosmin
      retention by the mitochondria was impaired in the entire left ventricular wall.
      The washout rate was further increased at all segments in the DC-like group
      versus the ASH group. Tetrofosmin retention by mitochondria was impaired in the
      entire left ventricular wall in the ASH group and was increased further in the DC
      like group. The dysfunction of myocardial cells was limited to the hypertrophied
      region in the apical HC group.

PMID- 11249893
TI  - Relation of heart rate and blood pressure turbulence following premature
      ventricular complexes to baroreflex sensitivity in chronic congestive heart
      failure.
AB  - Reduced heart rate variability (HRV) and attenuated baroreflex sensitivity (BS)
      after myocardial infarction and in patients with chronic congestive heart failure
      (CHF) are associated with poor prognosis. Recent studies have shown that a large
      proportion of the prognostic power from HRV measurements is localized in heart
      rate turbulence immediately after ventricular premature complexes. The mechanism
      of heart rate turbulence remains unknown. In the present study, we explore its
      relation to BS. In 45 patients with CHF and > or =3 ectopic beats in a 30-minute
      period, measurements of RR interval and continuous, noninvasive blood pressure
      (BP) were studied at rest. In response to an ectopic beat, average heart rate
      turbulence was 9.4 ms/beat (SD 6.1). Mean BP turbulence was 0.72 mm Hg/beat (SD
      0.56). Using the ratio of heart rate and BP turbulence slopes to estimate BS
      showed good agreement (r = 0.67, p < 0.0001) with the alpha-index method
      (BSalpha). This relation was attributable to a marked correlation between heart
      rate turbulence and BSalpha (r = 0.70, p <0.0001); there was no correlation
      between BP turbulence and the BSalpha (r = 0.1, p = NS). Twenty-nine percent of
      patients had postectopic pulsus alternans, with a mean decay time of 1.4 beats
      (SD 0.5). The presence of pulsus alternans was associated with a significantly
      lower heart rate turbulence slope (6.3 [SEM 1.0] vs 10.7 [SEM 1.2] ms/beat, p =
      0.03). Thus, heart rate turbulence is an effective measure of the baroreflex,
      correlating strongly with a standard measure. This is because it is the heart
      rate, rather than the BP, response to an ectopic beat that conveys the
      information relevant to BS measurement.

PMID- 11249895
TI  - Left ventricular remodeling and mechanics after successful repair of aortic
      coarctation.
AB  - Forty normotensive patients (mean age 12.3 +/- 6.5 years) followed up after a
      successful repair of aortic coarctation (mean age at coarctectomy 5.1 +/- 4.8
      yrs) were studied by echo-Doppler to (1) evaluate left ventricular (LV)
      remodeling and endocardial and midwall mechanics, and (2) identify factors that
      might predispose to persistent abnormalities. Sex- and age-specific cutoff levels
      for LV mass/height2.7 and relative wall thickness were defined to assess LV
      geometry. To adjust for age-and growth-related changes in ventricular mechanics,
      all echocardiographic variables were expressed as a Z-score relative to the
      normal distribution. In addition, the smallest diameter of the aorta was assessed
      by magnetic resonance imaging and calculated as percent narrowing compared with
      the diameter of the aorta at the diaphragmatic level. In the study group, 24 of
      40 patients (60%) had normal LV geometry. Among the 16 patients (40%) with
      abnormal LV geometry, 5 (12.5%) had a pattern of concentric remodeling and 11
      (27.5%) an eccentric hypertrophy. LV hypertrophy was marked (LV mass index >51
      g/m2.7) in 5 of these patients. No patient had a pattern of concentric
      hypertrophy. LV contractility was increased (Z-score >95th percentile) in 28
      patients (70%) as assessed using the endocardial stress-velocity index. In
      contrast, LV contractility assessed using midwall stress-velocity index remained
      elevated (Z-score >95th percentile) in 15 patients (37.5%). The stepwise multiple
      logistic regression analysis was not able to detect any significant independent
      predictor of abnormal LV remodeling, including sex, age at surgical repair,
      length of postoperative follow-up, heart rate, body mass index, systolic and
      diastolic blood pressure, and smallest diameter of the aorta, as well as indexes
      of LV geometry (shape, mass, volume, mass/ volume ratio) and function (preload,
      afterload, pump function, and myocardial contractility). Thus, normotensive
      patients after surgical repair of aortic coarctation may be in an LV hyperdynamic
      cardiovascular state (more frequent in those who have undergone late repair) and
      have multiple patterns of LV geometry.

PMID- 11249897
TI  - Another scare about antihypertensive therapy.

PMID- 11249896
TI  - Exercise performance after the arterial switch operation for D-transposition of
      the great arteries.
AB  - Early- and intermediate-term results of the arterial switch operation for D
      transposition of the great arteries (D-TGA) are encouraging. However, questions
      remain about the long-term outcome for these patients, especially with regard to
      exercise performance. Preliminary studies have demonstrated normal endurance time
      on treadmills. However, data regarding aerobic capacity and cardiopulmonary
      function are lacking. We report the cardiopulmonary performance of 22 school-age
      patients with D-TGA who underwent the arterial switch operation. Outcome
      variables included maximal oxygen consumption (VO2), maximal cardiac index, and
      peak heart rate. Patient and procedure-related variables were assessed for their
      association with outcome variables using linear and logistic regression. The mean
      values of maximal VO2 (113 +/- 19% predicted) and maximal cardiac index (96 +/-
      18% predicted) were within normal limits for the pediatric population. Although
      the mean peak heart rate for the entire group (184 +/- 14 beats/min) was within
      normal limits, there were 7 subjects (32%) with chronotropic impairment.
      Significant ST-segment depression was seen in 2 subjects (9%). In regression
      analysis, surgery subsequent to the arterial switch was associated with lower
      maximal cardiac index (p = 0.01). Other variables were not significantly
      associated with maximal VO2, maximal cardiac index, and peak heart rate. In
      particular, chronotropic impairment was not significantly associated with maximal
      VO2 or maximal cardiac index. These findings demonstrate that cardiopulmonary
      performance during exercise is excellent after the arterial switch operation. The
      finding of ST-segment depression in some subjects supports the role of formal
      exercise testing in those patients participating in vigorous athletic activities.

PMID- 11249898
TI  - How should we manage suspected perioperative infarction after coronary bypass
      surgery?

PMID- 11249899
TI  - Tissue factor as a therapeutic target in coronary syndromes.

PMID- 11249900
TI  - Comparison of baseline data, initial course, and management: losartan versus
      captopril following acute myocardial infarction (The OPTIMAAL Trial). OPTIMAAL
      Trial Steering Committee and Investigators. Optimal Trial in Myocardial
      Infarction with the Angiotensin II Antagonist Losartan.
AB  - The OPTIMAAL study was a multicenter, double-blind, randomized, parallel, trial
      in high-risk patients who were treated early after acute myocardial infarction
      that compared treatment with an angiotensin-converting enzyme inhibitor
      (captopril) and a selective angiotensin II antagonist (losartan) on survival and
      morbidity. A total of 5,477 patients with heart failure during the acute phase or
      with a new Q-wave anterior infarction or reinfarction were recruited. This study
      describes the baseline data and initial course of the cohort and compares these
      data and patient management across countries.

PMID- 11249901
TI  - Effect of concomitant or very early statin administration on in-hospital
      mortality and reinfarction in patients with acute myocardial infarction.
AB  - In a retrospective analysis, 66 patients identified as having received a statin
      drug within 24 hours of admission for acute myocardial infarction were matched
      3:1 with a control group of 198 patients not treated with a statin agent. End
      points of in-hospital mortality and in-hospital reinfarction were significantly
      lower in the statin-treated group, pointing to a benefit from very early statin
      treatment in acute myocardial infarction.

PMID- 11249902
TI  - Relation of soluble and platelet P-selectin to early outcome in patients with
      acute myocardial infarction after thrombolytic therapy.
AB  - Pre- and post-treatment platelet and soluble P-selectin were measured in a group
      of patients enrolled in the GUSTO-III study and were correlated with clinical
      outcomes. A peak in soluble P-selectin levels at 3 hours after thrombolytic
      therapy and lower baseline platelet P-selectin were associated with successful
      thrombolysis.

PMID- 11249903
TI  - Usefulness of oral dipyridamole therapy for angiographic slow coronary artery
      flow.
AB  - We evaluated the efficiacy of oral diypridamole therapy for the normalization of
      angiographically determined slow coronary artery flow. Diypridamole, which has
      dilatator properties on coronary microvessels, proved to be an effective
      treatment in most patients with slow coronary artery flow.

PMID- 11249904
TI  - Effect of beta blockers on incidence of new coronary events in older persons with
      prior myocardial infarction and diabetes mellitus.
AB  - Of 613 persons, mean age 79 +/- 9 years, with prior myocardial infarction and
      diabetes mellitus, 68 (11%) had contraindications to beta blockers; 289 of 545
      persons (53%) without contraindications to beta blockers were treated with beta
      blockers. The Cox regression model showed that significant independent predictors
      of new coronary events were age (risk ratio 1.02 for an increment of 1 year of
      age), systemic hypertension (risk ratio 2.0), serum low-density lipoprotein
      cholesterol > or =125 mg/dl (risk ratio 1.4), serum high-density lipoprotein
      cholesterol < or =35 mg/dl (risk ratio 1.6), and use of beta blockers (risk ratio
      0.73).

PMID- 11249905
TI  - Incidence, risk factors, and clinical outcome of stroke after acute myocardial
      infarction in clinical practice. MIR and MITRA Study Groups.  Myocardial
      Infarction Registry. Maximal Individual Therapy in Acute Myocardial Infarction .
AB  - In this analysis of ischemic and hemorrhagic strokes after acute myocardial
      infarction (AMI) in 21,330 consecutively included patients with AMI, we found an
      incidence of stroke after AMI of 1.2% and a very poor prognosis. Previous stroke,
      atrial fibrillation, and older age were the strongest predictors of stroke after
      AMI; thrombolysis was a borderline risk factor and early therapy with aspirin was
      associated with a reduction in stroke after AMI.

PMID- 11249906
TI  - Effectiveness of transluminal extraction atherectomy for debulking saphenous vein
      graft in-stent restenosis.
AB  - Treatment of in-stent restenosis in saphenous vein grafts often requires initial
      debulking, but transluminal extraction catheter (TEC) atherectomy is seldom used
      for this purpose, and most discussions omit this option. Our experience with 6
      episodes of TEC used successfully for saphenous vein graft in-stent restenosis
      and review of 7 other reported cases suggests TEC may be safe and effective for
      debulking saphenous vein graft restenosis lesions.

PMID- 11249907
TI  - The 6Fr Angio-Seal arterial closure device: results from a multimember
      prospective registry.
AB  - Femoral closure devices help early ambulation after cardiac catheterization
      without incurring additional risk to the patients. This report summarizes the
      safety and efficacy data of the 6Fr Angio-Seal device.

PMID- 11249908
TI  - High apolipoprotein B with low high-density lipoprotein cholesterol and normal
      plasma triglycerides and cholesterol.
AB  - Increased numbers of small, dense low-density lipoprotein particles may be
      present in patients with low high-density lipoprotein cholesterol and normal
      plasma triglycerides and cholesterol. Measurment of apolipoprotein B is the key
      to diagnosis and such patients should be considered for statin therapy.

PMID- 11249909
TI  - Circadian variation of paroxysmal atrial fibrillation. PA3 Investigators. Atrial
      Pacing Peri-ablation for Prevention of Atrial Fibrillation Trial.
AB  - The circadian variation of paroxysmal atrial fibrillation (AF) was studied in 67
      patients who received a dual-chamber pacemaker 3 months before a planned
      atrioventricular node ablation. A distinct circadian variation of AF was observed
      with 2 time peaks in initiation (1 in the early morning and 1 in the early
      evening hours), which was modulated by atrial pacing, the duration of AF, and the
      use of beta-adrenergic blocking agents.

PMID- 11249910
TI  - Usefulness of handgrip to improve ibutilide efficacy in organizing atrial
      electrical activity during atrial fibrillation.
AB  - We analyzed the effect of handgrip on atrial electrical activity during atrial
      fibrillation (AF) by recording right and left atrial activity in 15 patients with
      persistent AF under baseline conditions and after saline and ibutilide infusions.
      The handgrip test for 15 seconds, which was always associated with a significant
      increase in mean atrial cycle length, was recorded in both atria (right atrium:
      saline vs saline + handgrip 141 +/- 29 vs 171 +/- 24 ms, p <0.001; ibutilide vs
      ibutilide + handgrip: 197 +/- 43 vs 221 +/- 39 ms, p <0.005). Handgrip favorably
      modifies atrial electrophysiologic properties during AF.

PMID- 11249911
TI  - Electrophysiologic effects and efficacy of intravenous propafenone in terminating
      atrioventricular reentrant tachycardia in children.
AB  - In pediatric patients with atrioventricular reentrant tachycardia, intravenous
      propafenone exhibits its electrophysiologic effects in a dose-dependent manner by
      slowing or blocking retrograde conduction at the accessory connection. The high
      drug efficacy (81%) in terminating tachycardia is not dependent on patient age or
      retrograde conduction properties of the accessory connection.

PMID- 11249912
TI  - Plasma levels of vascular endothelial growth factor and its soluble receptor
      (SFlt-1) in essential hypertension.
AB  - In this study of 27 untreated patients with uncomplicated essential hypertension,
      we report on elevated plasma levels of vascular endothelial growth factor and its
      soluble receptor Flt-1 compared with healthy controls; these increased levels are
      reduced by the treatment of hypertension. This raises the possibility that
      abnormal angiogenesis may contribute to the pathogenesis of complications related
      to hypertension and merits exploration in larger studies.

PMID- 11249913
TI  - Rate of progression of valvular aortic stenosis in patients > or = 60 years of
      age.
AB  - A retrospective analysis of 171 women and 119 men, mean age 76 +/- 9 years, with
      aortic stenosis diagnosed by Doppler echocardiography, who had follow-up Doppler
      echocardiograms, showed that the reduction in aortic valve area per year was not
      significantly different in older persons with mild, moderate, and severe aortic
      stenosis. The decrease in aortic valve area per year was significantly greater in
      men 60 to 74 years old than in women 60 to 74 years old (p = 0.025), in women >
      or =75 years old than in women 60 to 74 years old (p = 0.006), and in persons
      with mitral annular calcium than in persons without mitral annular calcium (p =
      0.046).

PMID- 11249914
TI  - Prognostic value of an abnormal signal-averaged electrocardiogram in patients
      with nonischemic dilated cardiomyopathy.
AB  - The usefulness of an abnormal signal-averaged ECG (SAECG) for the risk
      stratification of patients with dilated cardiomyopathy was studied prospectively
      in 76 patients. Multiple analysis showed that an abnormal SAECG predicted cardiac
      mortality (p = 0.0046), sudden cardiac death, and the need for resuscitation (p =
      0.003); however, it did not predict death from heart failure and heart
      transplantation.

PMID- 11249915
TI  - Aortic dissection and patent ductus arteriosus in three generations.
AB  - Aortic dissection was found in a woman, her 2 sons, and 1 of her 3 daughters, and
      the 3 affected children and a granddaughter had patent ductus arteriosus. The
      pattern of inheritance of this unique syndrome probably is an autosomal dominant
      one.

PMID- 11249916
TI  - Effect of pravastatin on plasma markers of inflammation and peripheral
      endothelial function in male heart transplant recipients.
AB  - Statins appear to have several biologic effects beyond those of lipid metabolism,
      and we hypothesized that immunomodulating effects of statins are important for
      the beneficial effects of these medications after heart transplantation. Our
      findings suggest that pravastatin treatment reduces plasma markers of
      inflammation and improves peripheral endothelial function in heart transplant
      recipients, possibly contributing to the observed clinical benefits of statin
      treatment in these patients.

PMID- 11249917
TI  - Correlations of growth hormone (GH) and insulin-like growth factor I (IGF-I):
      effects of exercise and abuse by athletes.
AB  - The importance of hormones on body metabolism when physical exercise is carried
      out has been established for a long time. Growth hormone (GH) is crucial in
      energy metabolism as well as in body anabolism. Recent studies have increased our
      knowledge of GH's mechanisms of action. In particular, insulin-like growth factor
      I (IGF-I), the main hormone mediating the principal GH effects and other protein
      structures (i.e. the binding proteins related to these two hormones), has been
      recognized as playing a crucial role. The biochemical aspects relating to the
      molecules of the GH/IGF-I axis have been described here. Furthermore, the belief
      that GH and IGF-I enhance performance has induced an 'abuse' of GH (and possibly
      of IGF-I) by competitive sports athletes and amateurs. The present study outlines
      the best methods available to uncover abuse, as well as a series of potential
      research projects to recognize doping. The review also underlines the principal
      variables measurable in the laboratory and summarizes published reference ranges
      of these parameters. These biochemical and laboratory profiles describe principal
      experimental approaches, with the hope that this will stimulate new ideas on the
      subject of detecting doping practices.

PMID- 11249918
TI  - Serum cholesteryl ester transfer protein concentrations in healthy Chinese
      subjects and cardio-cerebrovascular disease patients.
AB  - Serum cholesteryl ester transfer protein (CETP) concentration was measured in
      1128 healthy Chinese subjects using a "sandwich" enzyme immunoassay and was 1.84
      +/- 1.55 mg/l (mean +/- S.D.). The frequency distribution of CETP in healthy
      subjects was markedly skewed towards low concentrations. The CETP concentration
      in females was significantly higher than that in males (2.40 +/- 1.65 mg/l vs.
      1.49 +/- 1.37 mg/l, P < 0.001). There was a weak inverse correlation between the
      CETP concentration and age (r = -0.19, P < 0.001). The CETP concentrations were
      significantly higher in 117 myocardial infarction (MI) survivors and 110 stroke
      patients than that in 335 healthy, age-matched males (1.98 +/- 1.68 173 +/- 1.45,
      and 1.40 +/- 1.37 mg/l respectively, P < 0.01), while no relation was found
      between CETP concentration and lipids concentration in MI, stroke and healthy
      group.

PMID- 11249920
TI  - Screening for primary hyperparathyroidism (PHPT) in clinic patients: differential
      diagnosis between PHPT and malignancy-associated hypercalcemia by routine blood
      tests.
AB  - Screening for primary hyperparathyroidism (PHPT) by measurement of the serum
      calcium concentration detects one patient per 500-1000 individuals in Western
      countries, and one patient per 2500-5000 subjects in Japan. Among clinic
      patients, however, the presence of many false-positive cases due to malignancy
      associated hypercalcemia (MAH) reduces the benefit of such screening. We
      evaluated a new method of screening for PHPT based on the results of routine
      blood tests using the hospital information system (HIS) at our hospital. This new
      method could distinguish PHPT from MAH. This study included 25179 blood samples
      in which the serum calcium (Ca), albumin (Alb), chloride (Cl) and inorganic
      phosphate (IP) concentrations had been measured between March, 1994 and February,
      1995 at Osaka University Medical Hospital. The HIS was programmed to pick blood
      samples that satisfied Formula 1 [Ca(mEq/ml) > 0.3 x Alb(g/dl) + 4.1] and Formula
      2 ([Cl(mEq/ml)-84] x [10 x Alb-15]/[IP(mg/dl)/3.1] > 400). Of data from 25179
      blood samples collected, those from 54 patients satisfied both Formulae 1 and 2.
      The patients from which these samples were derived from were subject to further
      analysis: medical records were studied and the intact-parathyroid hormone
      concentration was measured if necessary. Of these 54 cases, 19 patients (35.2%)
      were subsequently diagnosed with PHPT, including two, who were newly diagnosed
      with PHPT by this screening procedure. Although 35 (64.8%) of 54 patients were
      false-positive, many of them were treated with blood purification therapies in
      the Department of Pediatrics or the Intensive Care Unit (ICU). On the other hand,
      there were four false-positive cases (7.4%) caused by MAH. False-negative case in
      this study was only one patient (5%), whose diagnosis was normocalcemic PHPT.
      When omitting samples from pediatric patients and those in ICU, this screening
      procedure for PHPT has the advantage of being able to differentiate this
      diagnosis from MAH.

PMID- 11249919
TI  - Tumour markers in serum, bronchoalveolar lavage and biopsy cytosol in lung
      carcinoma: what environment lends the optimum diagnostic yield?
AB  - BACKGROUND: The aim of this study was to assess the diagnostic yield of the
      tumour markers carbohydrate antigen (CA 125), carcinoembryonic antigen (CEA),
      neuron-specific enolase (NSE), squamous cell carcinoma antigen (SCC) and specific
      tissue polypeptide antigen (TPS) in serum, bronchoalveolar lavage (BAL) and
      biopsy cytosol in a group of patients with bronchogenic carcinoma. METHODS:
      Serum, BAL and biopsy cytosol samples were collected in a group of 85 patients
      with benign or malignant pulmonary diseases. After appropriate processing, tumour
      markers were determined by enzyme immunoassay. The diagnostic yields
      (sensitivity, specificity and accuracy) in each environment (serum, BAL or
      biopsy) were obtained by using "ROC" curves. RESULTS: Determined individually, CA
      125, NSE and SCC show the greatest diagnostic accuracy in cytosol. CEA and TPS do
      so in BAL. CEA is the most relevant marker in serum and BAL, and CA 125 in
      cytosol. When the different tumour markers are associated, they offer better
      overall yields for all except TPS. CONCLUSIONS: For the factors evaluated in this
      study, determination of CEA in BAL was clinically the most useful marker in
      comparison with serum and cytosol determinations, although the latter may also be
      helpful in certain situations. Although there is no specific tumour marker for
      lung cancer, the combination of several can be used to monitor most patients with
      lung cancer.

PMID- 11249921
TI  - Fast, simple and cost-effective determination of thiopental in human plasma by a
      new HPLC technique.
AB  - BACKGROUND: Thiopental is an anaesthetic drug that is largely used in both short
      term and long-term infusion. After long-term infusion of thiopental, non-linear
      and inter-individual-dependent pharmacokinetics occur because of the saturation
      and/or induction of the metabolism. Clinical monitoring is important so that
      therapeutic adjustments can be made in many of the different pharmacological
      treatments, especially when long-term infusion is required. We describe a new,
      rapid HPLC method for the determination of plasma thiopental. METHODS: Sample
      preparation involved precipitation of plasma proteins using a mixture of
      methanol, zinc sulfate and ethylene glycol, and containing the internal standard
      5-ethyl-5-p-tolyl-barbituric acid. After adding trichloroacetic acid, the sample
      was centrifuged and the supernatant was injected into a C(18) reversed-phase
      column. The mobile phase used was water-methanol-acetonitrile (50:40:10, v/v).
      The eluent was monitored at 290 nm. RESULTS: The calibration curve was linear
      from 0.2 to 100 microg/mL. Precision, calculated as the coefficient of variation
      (%), was in the range of 3.62-0.70% for the within-day assay and 5.77-1.51% for
      the between-day assay. The absolute recoveries obtained from supplemented samples
      were never less than 100%. CONCLUSIONS: This technique shows good reliability and
      seems to be suitable for a very fast and simple therapeutic monitoring of plasma
      thiopental.

PMID- 11249922
TI  - Bladder tumor antigen assay as compared to voided urine cytology in the diagnosis
      of bladder cancer.
AB  - BACKGROUND: The study was aimed at comparing the diagnostic accuracy of the
      quantitative bladder tumor antigen (BTA) TRAK immunoassay with exfoliative urine
      cytology in the detection of primary and recurrent bladder cancer. METHODS: The
      analysis was carried out on 194 high risk patients undergoing a diagnostic
      cystoscopy, 279 patients with previous history of transitional cell carcinoma
      awaiting a follow-up cystoscopy, and 45 healthy controls. Urine cytology was
      performed by a skilled cytopathologist on three consecutive samples. RESULTS: BTA
      TRAK values resulted significantly higher in tumor positive cases than in absence
      of bladder tumor for both groups of patients. Non neoplastic urothelial diseases
      as well as the absence of mucosal abnormalities were associated with a marked
      increase in BTA TRAK levels with respect to the control group. Overall
      sensitivity and specificity was 63 and 63% for BTA TRAK (cut-off 34 U/ml), and
      68.3 and 73.4% for urine cytology, respectively. The diagnostic advantage of
      urine cytology was maintained when patients were stratified by tumor grade.
      CONCLUSIONS: The clinical performance of the BTA TRAK in the detection of primary
      or recurrent bladder cancer is acceptable and reproducible as shown by similar
      results with previous reports, although urine cytology performed on three samples
      showed the highest sensitivity and specificity.

PMID- 11249923
TI  - Acetylcholinesterase in lumbar and ventricular cerebrospinal fluid.
AB  - BACKGROUND: Soluble acetylcholinesterase (AChE, E.C. 3.1.1.7.) is released by
      neurons, glial and meningeal cells into the CSF. AChE activity in cerebrospinal
      fluid (CSF) is altered in various disorders of the nervous system. The objects of
      this study are to define a reference range for CSF AChE activity in human lumbar
      CSF, to prove that the enzyme activity does not depend on the blood/CSF barrier
      function, and to provide information about AChE in ventricular CSF. In addition,
      drugs used in neurosurgical care have been examined for their in vitro effects on
      CSF AChE activity to exclude interference with the test system. METHODS: We
      tested the AChE activity in 64 lumbar CSF samples collected from a clinically
      healthy population and in 169 ventricular CSF samples obtained from 90
      neurosurgical patients. AChE activity was assayed with our inhibitor-free test
      procedure. RESULTS: The reference range determined for lumbar CSF AChE activity
      is 9.2-24.4 nmol/min per ml. Lumbar CSF AChE activity does not correlate with
      parameters characterising the status of the blood/CSF barrier. Ventricular
      puncture is only justified for underlying pathology making it impossible to
      provide reference data for ventricular CSF. Most measurements reveal ventricular
      enzyme activity below 4 nmol/min per ml. CONCLUSION: The results of this study
      suggest the utility of lumbar CSF AChE activity as a measure of specific
      secretory function in enzyme releasing cells of the nervous system.

PMID- 11249924
TI  - Quantified increases of cholesterol, total lipid and globotriaosylceramide in
      filipin-positive Niemann-Pick type C fibroblasts.
AB  - BACKGROUND: Niemann-Pick disease type C (NPC) is a neurovisceral lysosomal
      lipidosis caused in most cases by mutations in the NPC1 gene that codes for the
      cholesterol regulating NPC1 protein. METHODS: Cultured skin fibroblasts from 11
      NPC patients aged 0.25 to 34 years at diagnosis with different severity of
      neurologic and visceral involvement, diagnosed by the cytochemical filipin test
      for lysosomally stored cholesterol, were analyzed for lipid composition.
      Cholesterol and other lipids were separated on thin-layer chromatography from
      fibroblast total lipid extracts, quantified by densitometry and compared with the
      total cell lipid mass. RESULTS: Cholesterol concentration in the patient cells
      was 1.5 to 5-fold higher than normal and total lipids up to 2.4-fold normal.
      Cholesterol and total lipids were particularly high in cells from NPC patients
      aged less than about 6 years, and for the whole patient series the abundance of
      fibroblast cholesterol was correlated with the tentatively assessed clinical
      disease severity. The findings in NPC suggested that NPC1 protein has a role not
      only in the balance of cholesterol but also the distribution of the total cell
      lipid mass. Another increase found in the NPC cells was that of a minor lipid
      fraction, globotriaosylceramide (Gb3, known as a cell signalling glycolipid).
      Gb3, in the average of its very variable individual concentrations, was about 2.5
      fold higher in the NPC cell group as compared to normal or pathologic control
      group, but there was no correlation of Gb3 with the other lipid concentrations
      studied. CONCLUSIONS: For NPC diagnosis, the fibroblast cholesterol and total
      lipid quantification can be used as an alternative to the usual filipin test for
      lysosomal cholesterol, but both test methods are prone to equivocal results in
      cells from a small fraction of atypical NPC patients, where chemical testing in
      organ biopsies or mutational analysis of the NPC1 gene should be tried.

PMID- 11249925
TI  - Antioxidant enzyme activities and malondialdehyde levels related to aging.
AB  - BACKGROUND: Free oxygen radicals have been proposed as important causative agents
      of aging. We have evaluated age-related changes in antioxidant enzyme activities
      and lipid peroxidation. METHODS: We measured erythrocyte superoxide dismutase
      (SOD), catalase (CAT), glutathione peroxidase (GPx) and plasma malondialdehyde
      (MDA) levels. One hundred and seventy six healthy subjects were divided into five
      groups: Group 1 (n = 25; 0.2-1 year-old), Group 2 (n = 28; 2-11 years), Group 3
      (n = 23: 12-24 years), Group 4 (n = 40; 25-40 years), Group 5 (n = 60: 41-69
      years). RESULTS: SOD activities in Group 5 were significantly lower than in the
      other groups (P < 0.001). GPx and CAT activities and MDA levels in Group 5 were
      significantly higher than the other groups (P < 0.001, respectively). CAT
      activity in Group 4 was significantly higher than group 1 and group 2
      (respectively, P < 0.001), and in group 3 was high compared to Group 2 (P <
      0.001). There were negative correlations between SOD activities and age (P <
      0.001). Conversely, there were positive correlations between CAT, GPx and MDA
      levels and age (P < 0.001). CAT activities of women in Group 2 were found to be
      high compared to the men (P < 0.05). MDA levels of women in Group 5 were higher
      than in the male groups (P < 0.001). CONCLUSIONS: We found age-related
      differences in erythrocyte antioxidant enzyme activities. Furthermore,
      peroxidative injury is raised in the aging process.

PMID- 11249926
TI  - Blood glucose meter performance under hyperbaric oxygen conditions.
AB  - This study evaluated the accuracy of the Precision PCx (PCx) against another
      bedside blood glucose meter SureStepPro (SSP), which has been shown to be
      unaffected by high P(O(2)). Human blood samples were used to prepare plasma
      glucose (PG) concentrations over a range of 25-300 mg/dl (1.4-16.6 mmol/l).
      Samples were sequentially tonometered with two separate gas mixes at 1520 mmHg
      (203 kPa) to P(O(2)) values of 1200 and then 60 mmHg, allowing measurement of
      each blood sample at both P(O(2)) values. The SSP PG measurements were unaffected
      by high P(O(2)): compared with PG concentrations measured at a P(O(2)) of 60
      mmHg, the SSP readings at a P(O(2)) of 1200 mmHg were higher by only 1.3 +/- 6.5
      mg/dl (0.1 +/- 0.4 mmol/l). At a P(O(2)) of 60 mmHg, compared with the SSP, the
      mean bias and imprecision (S.D. of bias) of the PCx were 4.1 and 22.9 mg/dl (0.2
      and 1.3 mmol/l). At a P(O(2)) of 1200 mmHg, the bias and imprecision of the PCx
      were 47.9 and 35.1 mg/dl (2.7 and 2.0 mmol/l). Therefore, compared to the SSP,
      the PCx does not provide as accurate a measurement of PG in blood when used
      either at 760 mmHg (101 kPa) or inside the hyperbaric chamber at 1520 mmHg (203
      kPa).

PMID- 11249928
TI  - Acute in vivo chylomicron metabolism and postalimentary lipoprotein alterations
      in normolipidemic male smokers.
AB  - Increased postprandial lipemia has been stated as one of the mechanisms
      responsible for atherogenesis in smokers. We measured the postalimentary lipid
      response and the in vivo intravascular delipidation index of an artificial
      chylomicron emulsion in healthy adult smokers and controls. The blood was
      collected in the fasting state immediately after the smokers smoked one
      cigarette. The lipemia was measured 2, 4, 6 and 8 h postalimentarily in smokers
      (S, n = 8) and in non-smoking controls (C, n = 8) and the chylomicron metabolism
      rate was measured 2, 4, 6, 8, 12, 16, 20, 24 and 30 min after the injection of an
      artificial emulsion to S (n = 10) and to C (n = 10). The lipoproteins were
      isolated in the fasting period and 4 h after the fatty meal and their chemical
      composition in cholesterol, triglycerides, phospholipids and protein was
      determined. Smokers showed an increased lipolysis percentage value (mean +/-
      S.E.M.) of the artificial chylomicron (39.1 +/- 3.1) compared to controls (26.5
      +/- 3.3) and higher levels of HDL(2)-PL: 28.4 +/- 4.3 (S) versus 16.2 +/- 2.0 (C)
      mg/dl (mean +/- S.E.M.). In conclusion, the oral fat tolerance was not altered in
      smokers but an upregulation of the rate of metabolism of the TG-rich lipoproteins
      was elicited immediately after smoking one cigarette.

PMID- 11249927
TI  - Serum IgG and IgE antibodies against mold-derived antigens in patients with
      symptoms of hypersensitivity.
AB  - BACKGROUND: Exposure to mold in water-damaged buildings has been suggested to be
      responsible for various health problems such as hypersensitivity and upper
      respiratory tract diseases. However, only little information is available on
      possible diagnostic tools for examining mold-associated health problems. METHODS:
      We used recently developed immunofluorometric IgG and IgE assays (UniCAP) to
      examine serum IgG and IgE antibodies against mold-derived allergens from 70 mold
      exposed individuals with (n = 55) or without (n = 15) symptoms of sensitization.
      Controls were healthy individuals (n = 31) without any history of such exposure.
      RESULTS: The IgG titers exceeded the upper normal limits of control individuals
      (mean +/- 2 S.D.) in 35% of symptomatic men and in 25% of women. The IgG titers
      were usually higher in women than in men (P < 0.05) showing no significant
      association with the severity of symptoms. During follow-up of eight mold-exposed
      subjects for 9-12 months the IgG titers remained relatively constant. Elevated
      anti-mold IgEs were found in six (11%) of the exposed subjects who were all
      symptomatic. CONCLUSIONS: Measurements of anti-mold IgGs may help to confirm
      exposure in patients with hypersensitivity symptoms and evidence of mold growth
      in living or working environment. Some exposed symptomatic patients present IgE
      mediated responses. Combined measurements of IgGs and IgEs may prove to be of
      value in the comprehensive assessment and treatment of such patients.

PMID- 11249929
TI  - Excessive free radical generation in the blood of children suffering from asthma.
AB  - The aim of the present study is to evaluate the biochemical parameters in blood
      relevant to oxygen free radicals and antioxidant defenses in children with
      asthma. A total of 210 asthmatic children, aged 5-18 years, were studied at two
      different times, once during a severe episode of wheeze (during episode category)
      and the other after recovery (resting condition). A total of 180 healthy children
      participated in the study as age and sex matched healthy controls. Superoxide and
      hydroxyl radical assays were used as a measure of free radical formation.
      Antioxidant enzymes and free radical scavengers in blood were also assayed. Lipid
      peroxidation products were assayed in plasma and erythrocytes to evaluate the
      imbalance (if any) between oxidant (radical) formation and their inactivation.
      Serum IgE concentrations and peak expiratory flow rate (PEFR) were used as
      measures of allergic reactions and residual lung capacity, respectively.
      Excessive production of superoxide and hydroxyl radicals were noted in the blood
      cells in asthmatics and were correlated to the severity of disease measured as
      PEFR. Superoxide dismutase and free radical scavengers in blood were
      significantly lower in asthma, even during resting condition. The present
      observations endorse the correlation between disease severity and oxygen radical
      production in asthma subjects. Oxygen metabolites may play a direct or indirect
      role in the modulation of airway inflammation. Excessive superoxide and hydroxyl
      radical production may be used as a marker for susceptibility to asthma and for
      monitoring therapeutic measures.

PMID- 11249930
TI  - Immunological response to oxidized LDL occurs in association with oxidative DNA
      damage independently of serum LDL concentrations in dyslipidemic patients.
AB  - Oxidative modification of LDL induces immunogenic epitopes in the LDL molecule,
      and the presence of antibodies against oxidized LDL (anti-Ox-LDL) has been
      demonstrated in human sera. However, little is known about the clinical
      significance of anti-Ox-LDL. To elucidate a clinical relationship between the
      immunological response to oxidized LDL and cellular oxidative stress, we measured
      serum titers of anti-Ox-LDL in 45 unselected patients with hypercholesterolemia
      and serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), considered a biomarker of the
      oxidative damage to DNA. The anti-Ox-LDL titer was not correlated with the serum
      LDL-C concentration, but was correlated with the 8-OHdG concentration (r = 0.300,
      P < 0.05) in a simple linear regression. Multiple regression analysis indicated
      that 8-OHdG was independently correlated with anti-Ox-LDL (r = 0.429, P < 0.05),
      but no other variables, including LDL-C concentrations and smoking habit, were
      correlated with anti-Ox-LDL. In 16 subgroup patients, the concentrations of TC,
      TG and LDL-C decreased and the HDL-C concentration increased after cholesterol
      lowering therapy with fluvastatin. In addition, both the anti-Ox LDL titer (14.0
      +/- 9.5 to 11.4 +/- 6.6 AcU/ml, P < 0.05) and the 8-OHdG concentration (1.19 +/-
      0.41 to 0.85 +/- 0.43 ng/ml, P < 0.05) also decreased after fluvastatin therapy.
      The immunological response to LDL oxidation on vascular wall tissues or cells
      appear to occur in association with oxidative DNA damage. The measurement of anti
      Ox-LDL may be a useful indicator for lipid-lowering therapy.

PMID- 11249931
TI  - Antioxidant defense status of red blood cells of patients with beta-thalassemia
      and Ebeta-thalassemia.
AB  - Anemia in beta-thalassemia is caused by a combination of ineffective
      erythropoiesis and premature hemolysis of RBC in the peripheral circulation.
      Excess of the alpha-globin chain present in beta-thalassemic RBC is mainly
      responsible for oxidative damage of erythrocyte membrane protein. The activities
      of glucose-6-phosphate dehydrogenase, glutathione reductase, glutathione
      peroxidase, and glutathione-S-transferase, and the catalytic activity of catalase
      and superoxide dismutase, and the concentrations of non-enzymic antioxidants such
      as reduced glutathione were measured to estimate the status of the antioxidant
      defense system in the erythrocytes for protection against oxidative stress. The
      extent of lipid peroxidation was also estimated in thalassemic erythrocytes.
      Significantly lower activities of reduced glutathione indicate the cell to be in
      a pro-oxidant state and decreased activity of catalase favors hydrogen peroxide
      mediated lipid peroxidation in beta-thalassemic and Ebeta-thalassemic RBC.

PMID- 11249932
TI  - Gender differences in exercise-induced changes in sex hormone levels and lipid
      peroxidation in athletes participating in the Hawaii Ironman triathlon. Ginsburg
      gender and exercise-induced lipid peroxidation.
AB  - BACKGROUND: Exercise reduces the risk of coronary heart disease in men and women
      but paradoxically, may promote free-radical formation, lipid peroxidation and
      vascular tissue injury. In this study, we assessed whether exercise-induced
      oxidative stress similarly affected men and women who participated in the Hawaii
      Ironman triathlon. METHODS AND RESULTS: Fifty-seven athletes (38 males) who
      completed the triathlon (3.9 km swim, 180.2 km bike, 42.2 km run) participated in
      this study. Blood samples were obtained 2 days before and immediately after the
      triathlon for the measurement of lipids, antioxidants and sex hormones and for
      the assessment of the susceptibility of plasma lipids to peroxidation. Lipid
      changes after exercise were similar for men and women. However, the
      susceptibility of plasma lipids to peroxidation was reduced by 61% (P < 0.001) in
      men and only 14% (P = NS) in women postrace. These changes were not associated
      with the supplemental use or levels of antioxidants. In addition, in men there
      was an increase of 58% in the antioxidant sex hormone estradiol and a decrease of
      58% in testosterone (P < 0.001) postrace. No significant changes were noted for
      these two hormones in women. CONCLUSIONS: There are significant gender-specific
      differences in the susceptibility of lipids to peroxidation and in changes in
      estradiol and testosterone levels as a result of ultra-endurance exercise. These
      changes may in part explain the salutary effect of exercise on the development of
      vascular disease.

PMID- 11249933
TI  - Preparation and value assignment of Standard Reference Material 968c Fat-Soluble
      Vitamins, Carotenoids, and Cholesterol in Human Serum.
AB  - Standard Reference Material 968c Fat-Soluble Vitamins, Carotenoids, and
      Cholesterol in Human Serum provides certified values for retinal, delta-, gamma-,
      and alpha-tocopherol, trans- and total beta-carotene, and cholesterol in human
      serum. Values are also reported for 16 additional compounds including lutein,
      zeaxanthin, alpha- and beta-cryptoxanthin, lycopene, alpha-carotene, retinyl
      palmitate, and 25-hydroxyvitamin D. The certified values for the fat-soluble
      vitamins and carotenoids in SRM 968c were based on the agreement of results from
      the means of at least two liquid chromatographic methods used at the National
      Institute of Standards and Technology (NIST) and from the medians from an
      interlaboratory comparison study among institutions that participate in the NIST
      Micronutrients Measurement Quality Assurance Program. The assigned values for
      cholesterol in the SRM are the means of results obtained using the NIST
      definitive method, gas chromatography-isotope dilution mass spectrometry.

PMID- 11249934
TI  - Arginase isoforms in human colorectal cancer.
AB  - Arginase (EC 3.5.3.1) activity was determined in 54 colorectal tissues obtained
      from patients with primary colorectal adenocarcinoma as well as in serum of 45
      patients and 65 healthy individuals. In patients, the preoperative values of the
      mean serum arginase activity and the activity in colorectal tumors were much
      higher than in serum of healthy subjects and control tissues. Two isoforms of
      arginase, anionic and cationic, were identified in colorectal tissues (normal and
      cancerogenous), and only one, the cationic form, in serum. These arginases were
      different from the main human liver cationic arginase (pI 9.3). The anionic
      colorectal arginase was identical with the human liver anionic isoform (pI 7.7),
      and the cationic arginase from colorectal tissues and blood serum with the human
      kidney cationic enzyme (pI 8.9). The total activity and the level of protein of
      the cationic arginase in colorectal cancer was higher than in control tissue, and
      it was also higher in serum of patients with colorectal cancer than in healthy
      subjects. Thus, it can be concluded that the increased arginase activity in blood
      serum and colorectal cancer in studied patients was due to the raised level of
      the cationic arginase and this isoform seems to be a discriminating parameter for
      assessing the presence of colorectal cancer.

PMID- 11249935
TI  - Total urine antioxidant capacity.
AB  - Total antioxidant capacity has been determined for several body fluids and
      provides a convenient means to compare antioxidant defenses among patients with
      acute or chronic inflammatory illnesses. We have studied urine specimens from a
      control group and a variety of patients with hypertension and acute and chronic
      renal diseases using an ABTS antioxidant assay as described for blood. Other
      urine assays included fluorescence markers for advanced glycosylation end
      products (AGE) and di-tyrosine (di-tyr), protein, uric acid, and creatinine
      concentrations. Urine antioxidant activity was standardized against ascorbic
      acid. We found that both the lag time and the area under the curve (AUC) in the
      ABTS assay were highly correlated with one another and correlated with the
      protein and uric acid concentrations, except for those specimens collected from
      patients with acute renal failure (ARF). The lack of correlation in the ARF group
      was not associated with significant differences in lag time or AUC. Correlations
      were seen also between antioxidant parameters and fluorescence for AGE and di
      tyr. The results indicate that the predominant antioxidants in the urine of
      patients with acute renal failure differ from those found in the urine of
      individuals with hypertension and chronic nephropathies. The ABTS assay provides
      a convenient marker for the antioxidant content of urine.

PMID- 11249936
TI  - Digitoxin-like immunoreactivity in sera of mice after feeding with chinese
      medicine Chan Su: study of protein binding of Chan Su in normal sera, uremic sera
      and sera from patients with liver disease.
AB  - Traditional Chinese medicines are readily available without prescription from
      herbal drug stores. One such Chinese medicine, Chan Su, which is prepared from
      the skin gland of toads, has cardiotonic effect due to bufadienolides. Here we
      report rapid detection of the presence of Chan Su in blood using the fluorescence
      polarization immunoassay for digitoxin. In our study mice were fed with a dose of
      75 mg/kg of Chan Su and blood was drawn before, and 1 and 2 h after feeding. We
      observed significant digitoxin-like immunoreactivity in the sera. For example in
      one mouse the digitoxin-like immunoreactivity was undetectable before feeding
      with Chan Su, but was 19.7 ng/ml 1 h and 8.8 ng/ml 2 h afterwards. The apparent
      half-life of Chan Su is approximately 1 h in mice. In another experiment, we
      studied protein binding of Chan Su by measuring total and free Chan Su
      concentrations (ultrafiltrate prepared by using Centrifree Micropartition Filter,
      molecular weight cutoff: 30000 Da). Chan Su was strongly bound to serum proteins.
      We observed higher free fraction in uremic sera and sera from patients with liver
      disease. We identified albumin as one of the proteins that bind Chan Su in serum.

PMID- 11249937
TI  - Degradation of human brain natriuretic peptide (BNP) by contact activation of
      blood coagulation system.
AB  - Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) were added
      to venous blood samples from healthy volunteers, and incubated in tubes made of
      various materials. The residual immunoreactivity was measured with
      radioimmunoassay for BNP and ANP. In blood samples stored in glass tubes,
      immunoreactivity of ANP was more stable than that of BNP. In siliconized glass or
      PET tubes, however, BNP immunoreactivity was more stable than ANP. The activation
      of blood coagulation factors was evaluated from the kallikrein activity in
      plasma. Kallikrein activity was increased in plasma stored in glass tube while it
      was negligible in plasma stored in siliconized glass or PET tubes. In kaolin
      activated plasma, more rapid BNP degradation and higher kallikrein activity were
      observed. Our results indicated that the blood coagulation factors, especially
      kallikrein, played an important role in digestion of BNP.

PMID- 11249938
TI  - The incidence of restenosis following PTCA using a turbidimetric Lp(a)
      immunoassay without the influence of apo(a) size polymorphism.

PMID- 11249939
TI  - Different angiotensin II-forming pathways in human and rat vascular tissues.
AB  - We studied the angiotensin II-forming pathways in extracts from human and rat
      vascular tissues. In the extract from human artery, angiotensin I mainly
      converted to two products, angiotensin-(1-9) and angiotensin II, while in the
      extract from rat artery, the major angiotensin I products were angiotensin II and
      angiotensin-(5-10). The concentrations of angiotensin II and angiotensin-(1-9)
      generated in the human extract (1 mg protein/ml) after incubation for 30 min were
      3.2 and 2.5 nmol, respectively, and that of angiotensin II and angiotensin-(5-10)
      generated in the rat extract (1 mg protein/ml) were 0.28 and 2.3 nmol,
      respectively. In the extract from human vascular tissues, the angiotensin II
      formation was inhibited by 8% with lisinopril and by 95% with chymostatin. The
      other product, angiotensin-(1-9) was inhibited completely by carboxypeptidase
      inhibitor. In the extract from rat vascular tissues, the angiotensin II formation
      was suppressed to 4% by lisinopril, but not by chymostatin. The angiotensin-(5
      10) formation was completely inhibited by chymostatin. These findings suggest
      clearly that human vascular tissues contain two angiotensin II-forming enzymes,
      angiotensin-converting enzyme and chymase, but rat vascular tissues have no
      chymase-dependent angiotensin II-forming pathway.

PMID- 11249940
TI  - Novel splicing mutation of the PPOX gene (IVS10 + 1G-->A) detected by denaturing
      high-performance liquid chromatography.

PMID- 11249941
TI  - Insects in hypoxia.
AB  - Insects exhibit a remarkable array of adaptations that allow them to handle more
      or less severe hypoxia associated with numerous aquatic and terrestrial habitats.
      We consider these habitats and then discuss physiological, behavioral and
      morphological mechanisms that facilitate insect life under oxygen deprivation.
      Actually or potentially hypoxic habitats include aquatic systems, flood-prone
      soils and burrows, intertidal zones, ice encasement and high altitudes. Some
      microhabitats, including dung, carrion, mammalian alimentary canals, grain and
      wood, also are subject to hypoxia. Adaptations to hypoxia include the ability to
      switch from aerobic to anaerobic metabolic pathways (with attendant generation of
      end products), the ability to drastically attenuate basal metabolic rates,
      altered behaviors and enlarged tracheal system volumes. Research into the biology
      of hypoxia seems to be progressing from early observations of the abilities of
      some insects to withstand exposure to hypoxia or anoxia through studies of
      organismal mechanisms operating in hypoxia to detailed investigations of cellular
      and intracellular signaling processes. Our hope is this essay will help
      crystallize the emergent picture of this area for those interested in
      contributing to future research.

PMID- 11249942
TI  - Characterization of vitellogenin in the red imported fire ant, Solenopsis invicta
      (Hymenoptera: Apocrita: Formicidae).
AB  - Vitellin (VN) and vitellogenin (VG) profiles were analyzed in monogyne and
      polygyne colonies of the red imported fire ant, Solenopsis invicta. Non
      denaturing and SDS-polyacrylamide gel electrophoresis (PAGE) analyses indicated
      that the native VN was likely 350 kDa and comprised of two subunits in the
      molecular size range of 170-185 kDa. SDS-PAGE of hemolymph showed that the
      relative mobilities and subunit patterns of VG and VN were similar. VG was
      present in the hemolymph of reproductive queens; alate, virgin queens; and
      workers, but not in males. Anti-VN, prepared from polygyne egg homogenates,
      reacted with egg homogenates and with hemolymph VG from reproductive, monogyne
      and polygyne queens and alate, virgin polygyne queens. Analysis of circulating VG
      and ovarian development in alate, virgin queens showed that low levels of VG
      appeared by five days following adult eclosion, but egg development was not
      observed until seven weeks. VG was evident in newly inseminated queens, and
      increased steadily for the first three weeks following dealation. VG levels
      declined slightly near eclosion of the first workers (= nanitics) and dropped
      sharply after nanitic emergence at five weeks following dealation. Oocyte
      maturation peaked at days 15-25 following dealation, but otherwise remained low
      but steady. These studies provide the basis for future investigations into
      endocrine regulations of vitellogenesis in S. invicta queens.

PMID- 11249943
TI  - Direct and indirect sublethal effects of Galanthus nivalis agglutinin (GNA) on
      the development of a potato-aphid parasitoid, Aphelinus abdominalis (Hymenoptera:
      Aphelinidae).
AB  - Snowdrop lectin (Galanthus nivalis agglutinin, GNA), has been shown to confer
      partial resistance to two potato aphids Myzus persicae and Aulacorthum solani,
      when incorporated in artificial diet and/or expressed in transgenic potato. First
      tier laboratory-scale experiments were conducted to assess the potential effect
      of GNA on the aphid parasitoid Aphelinus abdominalis. GNA (0.1% w/v) was
      successfully delivered to Macrosiphum euphorbiae via artificial diet and induced
      a reduced growth rate and increased mortality compared to aphids fed a control
      diet. As aphid parasitoid larvae are endophagous, they may be exposed to GNA
      during their larval development and potential "chronic toxicity" on A.
      abdominalis was investigated. The amounts of GNA present in aphid and parasitoid
      tissues were estimated by western blotting. Results suggest that parasitoids
      excrete most of the GNA ingested. Sublethal effects of GNA on several parasitoid
      fitness parameters (parasitism success, parasitoid development and size,
      emergence success, progeny survival and sex ratio) were studied. No direct
      detrimental effect of GNA on A. abdominalis was observed. However, GNA had an
      indirect host-size-mediated effect on the sex ratio and the size of parasitoids
      developing in GNA-fed aphids. This work highlights the need to determine the
      exact "causes and effects" when assessing the ecological impact of transgenic
      plants on non-target beneficial insects. Such bioassays form the basis of a
      tiered risk assessment moving from laboratory studies assessing individuals
      towards field-scale experiments assessing populations.

PMID- 11249945
TI  - The endoparasitoid Cotesia kariyai (Ck) regulates the growth and metabolic
      efficiency of Pseudaletia separata larvae by venom and Ck polydnavirus.
AB  - It was previously demonstrated that parasitization by Cotesia kariyai caused a
      decrease in weight gain and food consumption in host larvae, resulting in a lower
      final weight for parasitized hosts. It is predicted that C. kariyai regulates the
      physiological condition of the host to obtain maximum food under restricted
      nutritional conditions. Approximate digestibility (AD) was higher following
      parasitization but the efficiency of conversion of digested food (ECD) of the
      parasitized hosts was lower. This suggests that resources available to the
      parasitoid larvae are enhanced in the parasitized hosts. We evaluated the
      physiological changes caused by injection of calyx fluid (polydnavirus) plus
      venom (C+V) in nonparasitized hosts. Injection of C+V into the nonparasitized
      hosts duplicated the effects of parasitism, namely it increased the AD and
      decreased the ECD. Furthermore, C+V injections elevated trehalose concentrations
      in nonparasitized host 7 to 10 d after injection (2nd stadium of the parasitoid
      larva). Protein content also increased on days 9 and 10 after C+V injection.
      These results suggest that the nutrients that parasitoid larvae require for their
      growth increase in the hemolymph of the host during the 2nd stadium of the
      parasitoid larva.

PMID- 11249944
TI  - A comparative study on hypertrehalosaemic hormones in the Hymenoptera: sequence
      determination, physiological actions and biological significance.
AB  - A new hypertrehalosaemic peptide (Tea-HrTH; pQLNFSTGWGG-NH(2)) was isolated from
      the corpora cardiaca (CC) of the sawfly Tenthredo arcuata. The hypertrehalosaemic
      peptides found in the CC of five Bombus species and the paper wasp Polistes
      fuscata were identical to the adipokinetic hormone II of the desert locust,
      Schistocerca gregaria (Scg-AKH-II). The hypertrehalosaemic peptides found in the
      yellowjacket Vespula vulgaris and the hornet Vespa crabro were identical to the
      adipokinetic hormone of the cricket, Gryllus bimaculatus (Grb-AKH).All species
      examined had a large storage crop which, when filled with honey, held up to one
      third of their total body weight. Overwintering queens of P. fuscata had large
      stores of carbohydrates and lipids in the abdomen, and were able to survive
      months of fasting. Workers of Bombus hortorum (bumble-bee), Apis mellifera (honey
      bee) and V. vulgaris had little or no fat body. These species could fly as long
      as sugar was present in their crops, but they stopped flying as the carbohydrates
      in the crop disappeared. There was no significant increase in the haemolymph
      carbohydrate titres after injections of CC extracts or corresponding synthetic
      peptides into workers of B. hortorum or into males and females of T. arcuata.
      There was a moderate increase in haemolymph carbohydrate titres when these
      peptides were injected into overwintering queens of P. fuscata and into workers
      of V. crabro, both with significant amounts of fat body. However, well-fed V.
      vulgaris workers, with very little fat body, also responded to their own
      hypertrehalosaemic peptide.

PMID- 11249946
TI  - Effect of freezing on the transmembrane distribution of ions in freeze-tolerant
      larvae of the wood fly Xylophagus cinctus (Diptera, Xylophagidae).
AB  - The present study shows that freezing of freeze-tolerant larvae of the wood fly
      Xylophagus cinctus caused Na(+), K(+) and Mg(++) to move to electrochemical
      equilibrium across the cell membranes. Na(+) and Mg(++) moved from the haemolymph
      into the cells, while K(+) moved the opposite way. The original distribution of
      ions was restored after the larvae were thawed. The transmembrane fluxes of ions
      were of the same magnitude in the frozen and thawed larvae. The redistribution of
      ions in the frozen larvae did not give rise to any apparent change in the volume
      of cells and haemolymph upon thawing, i.e. the redistribution of solutes appeared
      to be osmotically neutral.

PMID- 11249947
TI  - The response of a homochrome grasshopper, Oedipoda miniata, to the dark-colour
      inducing neurohormone (DCIN) of locusts.
AB  - The effect of the dark-colour-inducing neurohormone (DCIN=[His(7)]-corazonin) of
      locusts was investigated in nymphs of the grasshopper, Oedipoda miniata, which
      exhibit strong homochromy, but neither green-brown, nor phase colour
      polymorphism. Graded doses of synthetic DCIN were injected in 1 ul of olive oil
      into 0-24-h-old penultimate nymphs. DCIN induced dose-dependent darkening in the
      recipients, seen 4 days after injection (still in the penultimate nymphal
      instar), as well as in the subsequent last-instar nymphs. The dose-range obtained
      between discernible and maximum (almost black) darkening extended over three
      orders of magnitude, from 1 pmol to 1 nmol of DCIN. In spite of the darkening
      observed already in the penultimate nymphal instar, the exuviae in the moult from
      this to the last nymphal instar did not show marked dark patches. However, the
      exuviae of the next moult (from last-instar nymph to adult) showed such dark
      patches, which increased with the increase of the dose, revealing the presence of
      exocuticular melanin. We conclude that DCIN, or a very close peptide, is the
      endogenous hormone which plays the major or sole role in the control of
      homochromy of O. miniata and possibly also of other acridids which exhibit
      homochromy.

PMID- 11249948
TI  - Regeneration of cultured midgut cells after exposure to sublethal doses of toxin
      from two strains of Bacillus thuringiensis.
AB  - Toxin from two strains of Bacillus thuringiensis (Bt), AA 1-9 and HD-73, caused
      dose-dependent destruction of cultured midgut cells from Heliothis virescens
      larvae. HD-73 toxin was more effective although, at the doses used, not all cells
      were killed. After 2 days of exposure to 0.8 pg/ul AA 1-9 or 0.06 pg/ul HD-73,
      columnar and goblet cell numbers declined to ca 20% of controls. In contrast,
      stem and differentiating cells increased to 140-200% of controls. The dynamic of
      depletion and replacement depended on toxin type and concentration. Two days
      after toxin was washed out, ratios of cell types returned to approximate control
      levels, suggesting rapid population corrections in vitro. Regulation of the ratio
      of cell types in each population, and the rate of proliferation and
      differentiation of stem cells was induced by the cultured midgut cells
      themselves. Controls and cells treated with toxin from Bt strain AA 1-9 were
      stained using a polyclonal antibody to Lepidopteran midgut differentiation factor
      1 (MDF1). With Bt toxin, 1.5 times more cells stained for MDF1, suggesting
      increased synthesis of this differentiation factor during increased stem cell
      differentiation. The response of cultured midgut cells to Bt toxin injury is
      similar to injured vertebrate tissues dependent on stem cells for replacement and
      healing.

PMID- 11249949
TI  - Evidence of a neural loop involved in controlling spermathecal contractions in
      Locusta migratoria.
AB  - The control of spermathecal contractions in Locusta migratoria via a neural loop
      was demonstrated using mechanical stimulation and electrophysiological
      recordings. Extracellular electrophysiological recordings from the receptaculum
      seminis nerve (N2B2), which innervates the spermathecal sac, were conducted
      during mechanical stimulation of the genital chamber sensory cells. Activation of
      the genital chamber sensory cells, using a glass probe approximating the shape
      and size of an egg, was found to increase the action potential frequency and
      initiate bursts of action potentials if a tonic frequency of action potentials
      was present prior to stimulation. If the motor pattern initially consisted of
      bursts of action potentials, then mechanical stimulation of the genital chamber
      sensory cells resulted in an increase in firing frequency, in most preparations,
      with the bursting remaining. Removal of the probe from the genital chamber always
      returned the motor activity to that noted prior to sensory cell stimulation.
      Simultaneous electrophysiological recordings from both the left and right
      receptaculum seminis nerves (N2B2) revealed that the bursts of action potentials
      were coordinated, although individual action potentials were not coupled one to
      one. Activation of the genital chamber sensory cells also resulted in increases
      in spermathecal contraction frequency, an effect which was coordinated with the
      changes in motor activity. It is proposed that an egg in the genital chamber
      activates the sensory cells resulting in increases in spermathecal contraction
      frequency and the subsequent release of spermatozoa onto the micropyle of the egg
      for fertilization.

PMID- 11249950
TI  - Drosophila males transfer antibacterial proteins from their accessory gland and
      ejaculatory duct to their mates.
AB  - The male fruitfly, Drosophila melanogaster, transfers to his mate proteins that
      increase his reproductive success by causing changes in her behavior and
      physiology. Here we show that among the transferred proteins are ones with
      antibacterial activity. We performed Escherichia coli overlay assays of native
      PAGE or renatured SDS-PAGE of reproductive tissue extracts of wild-type or
      transgenic males deficient in accessory gland function. We detected a 28 kDa male
      accessory gland-derived protein and two ejaculatory duct-derived proteins all
      with antibacterial activity. Based on its gel mobility and tissue of synthesis,
      one of the ejaculatory duct proteins is likely to be andropin, a previously
      reported 6 kDa antibacterial peptide. All three proteins are transferred to
      females during mating. Therefore, they could assist in protecting the male's
      reproductive tract and, after transfer to the female, the female's reproductive
      tract or eggs against bacterial infection. Since seminal fluid proteins are
      transferred before the sperm, these antibacterial proteins may also protect sperm
      from bacterial infection.

PMID- 11249951
TI  - Formation of lipid reserves in fat body and eggs of the yellow fever mosquito,
      Aedes aegypti.
AB  - We examined the accumulation of lipids in adult females of the mosquito, Aedes
      aegypti. Females emerged with about 100 ug lipid in the fat body. With access to
      sugar water lipids increased over seven days to 300 ug. After a blood meal on day
      five, sugar-fed females accumulated 120-140 ug of lipids in their ovaries within
      2 days. At the same time the lipid content of the fat body decreased by 100 ug,
      indicating transfer of lipids from fat body to oocytes. Experiments in which fat
      body lipids were prelabelled support this conclusion. Label was transferred to
      oocytes: in mature oocytes the specific radioactivity of lipids was 80% of the
      specific radioactivity of prelabeled fat body lipids. Components of blood meals
      are also used to synthesize oocyte lipids. Fat bodies of females starved for four
      days had only 27 ug of lipids left. When these females were given a blood meal,
      they matured oocytes, although the number of ooyctes was reduced and ovaries
      contained only half the amount of lipids found in ovaries of females which had
      first fed on sugar water. Fat body lipids of these females had only slightly
      increased to 36 ug. This demonstrates that female Ae. aegypti use sugar to
      synthesize lipids, but they can also use components of blood for this purpose.

PMID- 11249952
TI  - Rubidium reduces potassium permeability and fluid secretion in Malpighian tubules
      of Locusta migratoria, L.
AB  - The basal membrane potential (V(b)) of Locusta Malpighian tubule cells in control
      saline results from its relatively high permeability to potassium. In the
      presence of 1 mM barium added to the control saline V(b) hyperpolarized from a
      mean resting potential of -72.1 mV to -90.1 mV. On substituting rubidium for
      potassium in the control saline, V(b) also hyperpolarized to a value of -91.4 mV.
      Rubidium was also similarly effective in hyperpolarizing the basal membrane even
      in the presence of control concentrations of potassium in the bathing medium.
      Substitution of rubidium for potassium also effected a approximately 50%
      reduction in the rate of fluid secretion. The action of inhibitors on V(b) in the
      presence of rubidium showed that V(b) under these conditions probably originated
      from the bafilomycin-sensitive electrogenic potential generated across the apical
      membrane by a V-type ATPase. The responses of V(b) to potassium, barium and
      rubidium and their inhibition of fluid secretion suggest the presence of a
      substantial rubidium-blockable potassium conductance located on the basal
      membrane of Locusta Malpighian tubule cells.

PMID- 11249953
TI  - Fate of an alkaloidal nuptial gift in the moth Utetheisa ornatrix: systemic
      allocation for defense of self by the receiving female.
AB  - In the moth Utetheisa ornatrix defensive pyrrolizidine alkaloids are sequestered
      by both sexes as larvae from their foodplants. The adult male transmits some of
      this alkaloid to the female at mating for eventual incorporation into the eggs.
      We now show by chemical analyses that the female herself is the first beneficiary
      of the alkaloid she receives from the male. By the end of mating the male's
      alkaloid is found already to be generally distributed throughout the female's
      body (including even the wings), while it is still largely absent from the
      ovaries. This result is in line with our earlier finding that the male's
      alkaloidal gift can itself suffice to render a female fully protected against
      spiders from the moment she uncouples from the male.

PMID- 11249954
TI  - "Leucokinin and the modulation of the shunt pathway in malpighien tubules" by
      Ming-Jiun Yu and Klaus W. Beyenbach. Journal of Insect Physiology 47(3) 263-276.

PMID- 11249956
TI  - Increased expression of neuronal Src and tyrosine phosphorylation of NMDA
      receptors in rat brain after systemic treatment with MK-801.
AB  - We have observed that systemic treatment with the uncompetitive N-methyl-D
      aspartate (NMDA) receptor antagonist MK-801 increases Src expression and NMDA
      receptor phosphorylation in rat brain. A partial cDNA encoding rat neuronal Src
      was isolated and its sequence was used to design specific oligonucleotide probes.
      Systemically administered MK-801 (5 mg/kg for 4 h) increased by 28+/-4% mRNA
      expression of neuronal Src in the superficial layers of the parietal cortex. This
      effect was observed at doses as low as 0.2 mg/kg. A similar, although more
      modest, induction was observed 6 h after phencyclidine (15 mg/kg) administration,
      but not after high doses of memantine and ketamine. The MK-801-induced effect was
      not blocked by pretreatment with clozapine. Consistent with the increase in mRNA
      levels, cortical Src protein was increased to 186 +/- 24% of control 24 h after
      MK-801 treatment. Total cellular Src activity was also increased in parietal
      cortex homogenates 4 h after MK-801 (5 mg/kg). Moreover, MK-801 treatment (0.5
      mg/kg and 5 mg/kg for 4 h) increased tyrosine phosphorylation, but not protein
      levels, of the NMDA receptor subunit NR2A. These results provide evidence for a
      contribution of Src and tyrosine phosphorylation of NMDA receptors in the
      pharmacological actions of uncompetitive NMDA receptor antagonists.

PMID- 11249957
TI  - Effects of competitive and non-competitive NMDA receptor antagonists on dopamine
      output in the shell and core subdivisions of the nucleus accumbens.
AB  - The effects of acute intravenous administration of the non-competitive NMDA
      receptor antagonists, phencyclidine (PCP), dizocilpine (MK-801; (+)-5-methyl
      10,11-dihydroxy-5H-dibenzo(a,b)cyclohepten-5,10-imine), and the competitive NMDA
      receptor antagonist CGP 39551 (DL-(E)-2-amino-4-methyl-5-phosphono-3-pentanoic
      acid) on extracellular dopamine concentrations were analyzed in the shell and
      core subdivisions of the nucleus accumbens (NAC), associated with limbic and
      motor functions, respectively. Extracellular dopamine concentrations were
      assessed utilizing differential normal pulse voltammetry in chloral hydrate
      anesthetized, pargyline pretreated rats. Intravenous administration of PCP (0.5
      mg/kg) or MK-801 (0.1 mg/kg) both significantly elevated extracellular dopamine
      levels in the NAC shell but not in the core. However, administration of
      relatively low doses of the competitive NMDA receptor antagonist CGP 39551 (2.5
      mg/kg) failed to affect dopamine output in either region. However, when a higher
      dose (10 mg/kg) was administered a significant elevation in dopamine output was
      obtained in the shell compared to the core. Our data demonstrate that non
      competitive NMDA receptor antagonists evoke an accumbal dopamine output that is
      selective to limbic cortical related NAC regions. This profile is shared also by
      competitive NMDA receptor antagonists when given in high, but not low doses. Our
      results are compatible with the reported elicitation of PCP-like behavioral
      effects by competitive NMDA receptor antagonists when administered in relatively
      high doses. Moreover, these findings suggest that differences in the regional
      accumbal dopamine output between competitive and non-competitive NMDA receptor
      antagonists may be essentially attributable to the relative degree of NMDA
      receptor antagonism achieved by the drugs. This experimental model may afford a
      biochemical means to assess the psychotomimetic liability of NMDA receptor
      antagonists, a side effect that may reduce their usefulness as neuroprotective
      agents.

PMID- 11249958
TI  - Distinct effect of pregnenolone sulfate on NMDA receptor subtypes.
AB  - Using rapid agonist applications to transfected HEK-293 cells, we investigated
      pregnenolone sulfate (PS) effects on deactivation and desensitization of
      recombinant NMDA receptors subtypes. PS prolonged the deactivation of responses
      produced by brief applications of L-glutamate with all subunit combinations
      tested. The action of PS was larger on NR1a/NR2A than on NR1a/NR2B channels. PS
      slowed the rate of macroscopic desensitization of the responses with all subunit
      combinations tested. In contrast, PS had little effect on current rise time and
      had much reduced action on responses with L-cysteate, a low affinity agonist. Our
      results suggest that PS decreases agonist unbinding. However, this action is
      counteracted by decreased desensitization. Since desensitization produces slow
      deactivating components, particularly with NR1a/NR2B receptors, this underlies
      the decreased PS effect with these subtypes. Indeed PS action was mainly observed
      on the fast component of deactivation. Furthermore, prolongation of NR1a/NR2A
      responses was similar to that of responses from NR1b/NR2B receptor, a subtype
      characterized by reduced desensitization. PS prolongation of evoked NMDA receptor
      mediated synaptic currents from cortical neuronal primary culture(s) was not
      significantly different from that of responses with NR1a/NR2B receptors
      indicating that native receptors in these neurons comprised at least some
      heteromeric combinations of these two subunits.

PMID- 11249959
TI  - Nitric oxide-induced potentiation of CA1 hippocampal synaptic transmission during
      baseline stimulation is strictly frequency-dependent.
AB  - Nitric oxide (NO) has been hypothesised to serve a signalling role in certain
      types of synaptic plasticity. If so, exogenously applied NO should be able to
      elicit those same plastic changes under appropriate conditions. In the case of
      hippocampal long-term potentiation (LTP), however, existing evidence is
      discrepant. Field recordings of synaptic transmission in the CA1 area of rat
      hippocampal slices were used to re-examine this issue. Under 0.2 Hz afferent
      fibre stimulation, NO (delivered using two different NONOates) produced,
      concentration-dependently, a depression of synaptic transmission. On washout of
      NO, the depression gave way to a persistent potentiation, the amplitude of which
      was also graded with NONOate concentration. Tetanus-induced LTP, induced an hour
      after washout, was occluded in proportion to the degree of prior NO-induced
      potentiation. At a lower stimulation frequency of 0.033 Hz, the depression was
      unaltered but no rebound potentiation took place and subsequent tetanus-induced
      LTP was normal. Tests indicated that there is a clear time-window during which
      0.2 Hz stimulation needs to be applied relative to the delivery of NO to produce
      a potentiation. The findings explain previous divergent results and indicate that
      exogenous NO-triggered potentiation depends critically on the frequency of
      synaptic transmission.

PMID- 11249960
TI  - Multiple 5-HT(1) autoreceptor subtypes govern serotonin release in dorsal and
      median raphe nuclei.
AB  - The present study investigated the possibility of multiple 5-HT(1) autoreceptor
      subtypes in the rostral raphe nuclei. Slices (350 microm) of rat dorsal or median
      raphe nucleus (DRN/MRN) were taken from male Wistar rats and superfused with
      artificial cerebrospinal fluid at 32 degrees C. Fast cyclic voltammetry at carbon
      fibre microelectrodes was used to monitor serotonin (5-HT) release following
      local electrical stimulation. In both DRN and MRN, 5-HT release on short trains
      was reduced by the selective 5-HT(1A) agonist 8-OH-DPAT (1 microM), an effect
      blocked by the selective 5-HT(1A) antagonist WAY 100635 (0.1 microM) but not by
      SB 216641 (0.05 and 0.2 microM) or BRL 15572 (0.5 microM), selective antagonists
      at the 5-HT(1B) and 5-HT(1D) receptors respectively. The selective 5-HT(1B)
      agonist CP 93129 (0.3 microM) also reduced 5-HT release in both nuclei. Its
      effect was blocked by SB 216641 but not by WAY 100635 or BRL 15572. The 5
      HT(1D/1B) agonist sumatriptan (0.5 microM) decreased 5-HT release in both DRN and
      MRN. In DRN, the effect of sumatriptan was blocked by BRL 15572 but not by WAY
      100635 or SB 216641. In MRN, the effect of sumatriptan was not blocked by any of
      the above antagonists. BRL 15572 increased 5-HT release on long stimulations in
      DRN and MRN while WAY 100635 had no effect. SB 216641 increased 5-HT release in
      MRN but not DRN. WAY 100635 potentiated the effect of SB 216641 in DRN but not
      MRN. The data suggest that 5-HT release in DRN is controlled by 5-HT(1A), 5
      HT(1B) and 5-HT(1D) autoreceptors. 5-HT release in MRN is controlled by 5-HT(1A)
      and 5-HT(1B) autoreceptors and another, as yet unidentified mechanism.

PMID- 11249961
TI  - 4991W93 inhibits release of calcitonin gene-related peptide in the cat but only
      at doses with 5HT(1B/1D) receptor agonist activity?
AB  - Calcitonin gene-related peptide (CGRP) is a marker for trigeminovascular
      activation and is released during the headache phase of migraine and cluster
      headache. CGRP may have a role in migraine through its potent cranial vasodilator
      effects, or by an action on trigeminal nerve activity, both of which are targeted
      by 5HT(1B/1D) agonist drugs. CP122,288, a conformationally restricted analogue of
      sumatriptan that is a potent inhibitor of neurogenic plasma protein extravasation
      (PPE), was ineffective at inhibiting CGRP release at a single low dose; and is
      also ineffective as an acute anti-migraine compound. However, it remained unclear
      as to whether, as a class, the conformationally-restricted triptan analogues
      could have inhibitory effects on CGRP in higher doses. 4991W93, a
      conformationally restricted analogue of zolmitriptan, is also a potent inhibitor
      of PPE at doses without 5HT(1B/1D)-mediated effects, that was developed as an
      anti-migraine drug, and thus was suitable to test whether higher doses of such
      conformationally restricted triptan analogues could inhibit trigeminal-evoked
      CGRP release. The superior sagittal sinus (SSS) was stimulated in 14
      anaesthetised cats and external jugular vein blood samples were analysed by
      radioimmunoassay for CGRP levels before, 1 min after SSS stimulation, and 1 min
      after SSS stimulation in the presence of 4991W93. Stimulation of the SSS resulted
      in release of CGRP from the external jugular vein. 4991W93 at a dose of 0.1 and
      10 microg/kg, selected for maximal PPE blocking effects in rodents, was
      ineffective at inhibiting CGRP release, with an SSS stimulation level of 78+/-4
      pmol/l compared to a post-4991W93 level of 79+/-3 pmol/l (n=4). In comparison
      CGRP release was inhibited after a dose of 100 microg/kg 4991W93 from 64+/-6 to
      36+/-3 pmol/l (n=5). Given that 4991W93 is inactive clinically at non-vascular
      doses, it seems clear that the 5HT(1B/1D) agonist effects of the compound are
      necessary for blockade of CGRP release and thus any anti-migraine action. Taken
      with the clinical results, these data emphasise the importance of CGRP release in
      migraine, and suggest that other non-5HT-based pharmacological targets may
      account for PPE blockade in animal studies.

PMID- 11249962
TI  - Substrates and temperature differentiate ion flux from serotonin flux in a
      serotonin transporter.
AB  - Neurotransmitter transporters couple the transport of transmitter against its
      concentration gradient to the electrochemical potential of associated ions which
      are also transported. Recent studies of some neurotransmitter transporters show
      them to have properties of both traditional carriers and substrate-dependent ion
      channels, in that ion fluxes are in excess of that predicted from stoichiometric
      substrate fluxes. Whether these properties are comparable for all transporters,
      the extent to which these permeation states are independent, and whether the
      relationship between these two states can be regulated are not well understood.
      To address these questions, we expressed the Drosophila serotonin (5HT)
      transporter (dSERT) in Xenopus oocytes and measured both substrate-elicited ion
      flux and 5HT flux at various temperatures and substrate concentrations. We find
      that the ion flux and 5HT flux components of the transport process have a
      significant temperature dependence suggesting that ion flux and transmitter flux
      arise from a similar thermodynamically-coupled process involving large
      conformational changes (e.g., gating). These data are in contrast to those shown
      for glutamate transporters, suggesting a different permeation process for 5HT
      transporters. The relationship between ion flux and 5HT flux is differentially
      regulated by chloride and 5HT, suggesting that these permeation states are
      distinct. The difference in half-maximal 5HT concentration necessary to mediate
      ion flux and 5HT flux occurs at submicromolar 5HT concentrations suggesting that
      the relative participation of dSERT in ion flux and 5HT flux will be determined
      by the synaptic 5HT concentration.

PMID- 11249963
TI  - Chronic elevation of brain GABA levels beginning two days after status
      epilepticus does not prevent epileptogenesis in rats.
AB  - Vigabatrin (VGB) treatment is neuroprotective in various models of status
      epilepticus (SE) and delays the development of kindling via mechanisms that are
      assumed to relate to the elevation of GABA levels in the brain. Here, we tested
      the hypothesis that a chronic elevation of brain GABA levels obtained by VGB
      treatment prevents the development of spontaneous seizures (i.e. epilepsy)
      following SE in rats. Self-sustained SE (SSSE) was induced by stimulating the
      lateral nucleus of the amygdala. Two days later, chronic VGB (75 mg/kg/day) or
      saline treatment was started via subcutaneous osmotic minipumps. The development
      of spontaneous seizures was monitored once a week (24 h at a time) using video
      EEG recording. Rats were perfused for histology either at the end of the 10-week
      drug treatment, or later at the end of an 8-week drug-free follow-up period.
      Before perfusion for histology, spatial learning and memory perform was tested in
      the Morris water-maze. Spontaneous seizures were observed in 55% (6/11) of the
      saline-treated and 73% (8/11) of the VGB-treated rats during the 10-week
      treatment period. Seizure frequency, severity, and duration were similar in VGB
      treated rats and controls during and after the drug-treatment period. VGB
      treatment did not decrease neuronal damage in various temporal lobe regions or
      mossy fiber sprouting. VGB treatment also did not attenuate spatial learning or
      memory impairments. These findings indicate that the augmentation of GABAergic
      neurotransmission by VGB does not prevent the development of epilepsy when
      treatment is started 2 days after SE.

PMID- 11249964
TI  - Functional characterisation of human TASK-3, an acid-sensitive two-pore domain
      potassium channel.
AB  - Human TASK-3 (hTASK-3) is a recently identified member of the two-pore domain
      potassium channel (2PDKC) family which in man is predominantly expressed in the
      cerebellum. Previous preliminary examination of this channel indicates that when
      expressed in Xenopus oocytes, it produces a K(+) selective background conductance
      and consequent shift in resting membrane potential, thus mimicking other 2PDKC.
      Here we describe some additional functional and pharmacological aspects of hTASK
      3-mediated conductances expressed in both Xenopus oocytes and HEK293 cells. hTASK
      3 expression produces steady-state currents that approximate Goldman--Hodgkin-
      Katz behaviour with respect to membrane potential. Despite this, voltage steps
      from -80 mV to potentials > approximately -20 mV induce currents that exhibit a
      clear time-dependent increase in current amplitude. Kinetically, this increase in
      current was well fit by a single exponential, the time constant of which was
      approximately 10 ms and appeared independent of test potential, between -20 and
      +80 mV. In HEK293 cells hTASK-3 currents were inhibited by extracellular acidosis
      with a mid-point for inhibition of pH 6.4. Furthermore, the activity of TASK-3
      was potentiated by the volatile anaesthetic halothane but inhibited by the local
      anaesthetic bupivacaine.

PMID- 11249965
TI  - Administration of myr(+)-G(i2)alpha subunits prevents acute tolerance
      (tachyphylaxis) to mu-opioid effects in mice.
AB  - The administration of efficacious doses of morphine or beta-endorphin causes
      acute tolerance (tachyphylaxis) to the effects of additional administrations of
      these opioids. Mice intracerebroventricularly (icv)-injected with biologically
      active myristoylated (myr(+))-G(i2)alpha subunits developed no tachyphylaxis to
      morphine antinociception in the tail-flick test. This treatment increased the
      potency of opioid-induced analgesia during the declining phase. Moreover, animals
      showing tachyphylaxis to opioid effects exhibited normal responses to the
      agonists after icv-administration of myr(+)-G(i2)alpha subunits. In morphine
      tolerant/dependent mice, an icv dose of 12 pmol/mouse myr(+)-G(i2)alpha subunits
      facilitated complete restoration of morphine antinociception in only 4 or 5 days
      instead of the 10 to 11 days required for post-dependent mice. This was observed
      when myr(+)-G alpha subunits were injected within the first 24 h of chronic
      morphine administration -- but not later when long-term tolerance takes place.
      These results suggest that during the course of an opioid effect a progressive
      reduction of receptor-regulated G-proteins occurs, and hence tachyphylaxis
      develops. Exogenous administration of myr(+)-G alpha subunits may be of
      therapeutic potential in improving agonist activity and accelerating the recovery
      of post-dependent receptors.

PMID- 11249966
TI  - Cannabinoidergic and opioidergic inhibition of spinal reflexes in the
      decerebrated, spinalized rabbit.
AB  - The present experiments were designed to investigate the role(s) of cannabinoid
      receptors in modulating transmission in the sural-medial gastrocnemius withdrawal
      reflex of the decerebrated, spinalized rabbit and how, if present, cannabinoid
      mediated control might interact with opioid-mediated inhibitions known to impinge
      on this reflex pathway. The selective CB(1) receptor antagonist SR 141716A
      enhanced reflexes by a factor of two after a cumulative dose of 100 nmol kg(-1)
      i.v., but had no effect on the endogenous opioid-mediated inhibition generated by
      repetitive electrical stimulation of the common peroneal nerve, or on the
      suppression of reflexes caused by i.v. administration of the synthetic opioid
      fentanyl. Given at a dose of 10 nmol kg(-1) i.v., the potent, CB(1)--CB(2)
      cannabinoid receptor agonist HU 210 inhibited medial gastrocnemius reflexes to
      approximately 30% of controls and significantly decreased both heart rate and
      blood pressure, but did not alter the inhibition of reflexes resulting from
      common peroneal nerve stimulation or i.v. fentanyl. The effects of HU 210 were
      reversed by SR 141716A. HU 210 was just as effective in inhibiting reflexes in
      the presence of the opioid antagonist naloxone (5 micromol kg(-1)) as it was in
      untreated animals. The data show that cannabinoids, acting through CB(1)
      receptors, are inhibitory in rabbit spinal cord and that there appears to be some
      endogenous cannabinoid tone under the conditions of the present experiments. The
      evidence of this study is that the inhibitory effects of opioids and cannabinoids
      in rabbit spinal cord are completely independent of each other, and are additive
      rather than synergistic.

PMID- 11249967
TI  - The novel analgesic, cizolirtine, inhibits the spinal release of substance P and
      CGRP in rats.
AB  - Although previous studies have established that cizolirtine (5-([(N,N
      dimethylaminoethoxy)phenyl]methyl)-1-methyl-1H-pyrazol citrate) is a potent
      analgesic in rodents, its mechanism(s) of action remain(s) unclear. In vitro and
      in vivo approaches were used to assess whether cizolirtine could affect the
      spinal release of two pain-related neuropeptides, substance P (SP) and calcitonin
      gene-related peptide (CGRP), in rats. Cizolirtine significantly reduced the K(+)
      evoked overflow of both the SP-like material (SPLM; -25% at 0.1 microM--0.1 mM)
      and CGRPLM (-20% at 0.1--1.0 microM) from slices of the dorsal half of the lumbar
      enlargement of the spinal cord. Intrathecal perfusion in halothane-anaesthetized
      rats showed that local application of cizolirtine markedly diminished the spinal
      outflow of SPLM (up to -50% at 0.1 mM) but only marginally that of CGRPLM.
      Systemic administration of cizolirtine at an analgesic dose (80 mg/kg i.p.) also
      reduced spinal SPLM outflow (-50%) but not that of CGRPLM. Under both in vitro
      and in vivo conditions, idazoxan (10 microM) antagonized the effects of
      cizolirtine on SPLM and CGRPLM release, suggesting their mediation through
      alpha(2) adrenoceptors.

PMID- 11249968
TI  - Somatostatin receptor subtype 1 (sst(1)) regulates intracellular 3',5'-cyclic
      adenosine monophosphate accumulation in rat embryonic cortical neurons: evidence
      with L-797,591, an sst(1)-subtype-selective nonpeptidyl agonist.
AB  - Somatostatin (SRIF) initiates its biological activities by interacting with five
      homologous G-protein-coupled receptor subtypes (sst(1--5)). In the mammalian
      nervous system, sst(1--5) receptor mRNA expression patterns have been localized
      by in situ hybridization studies, or at the protein level with receptor-specific
      antibodies. Cortical responses to SRIF have been demonstrated, although a
      functional relationship between an SRIF effect and an individual receptor subtype
      is lacking. The recent development of novel, subtype-selective SRIF receptor
      ligands now provides a means to correlate receptor subtype expression patterns
      with the corresponding biological function. In cultured monolayers of E17-18 rat
      embryonic cortical neurons, 10(-7) M SRIF-28 inhibited 10(-6) M forskolin
      stimulated cAMP accumulation by 37%, a level of inhibition that was mimicked by L
      797,591, a potent sst(1)-selective agonist. SRIF-14 or L-797,591 inhibited
      forskolin-stimulated cAMP accumulation in a concentration-dependent fashion, with
      EC(50)s (effective concentration for 50% maximal response) of 8.0 x 10(-10) M and
      7.0 x 10(-10) M, respectively. No similar concentration-dependent effect on
      forskolin-stimulated cAMP levels was observed with sst(2)-, sst(3)- or sst(4)
      selective agonists. Furthermore, both SRIF-14 and L-797,591 inhibited 10(-7) M
      CRH-induced cAMP in the embryonic neurons. These results are the first evidence
      demonstrating that sst(1) regulates intracellular cAMP levels in embryonic
      neurons and may inhibit CRH-mediated effects in the embryonic cortex.

PMID- 11249969
TI  - An alpha(2)-adrenergic antagonist, atipamezole, facilitates behavioral recovery
      after focal cerebral ischemia in rats.
AB  - Previous studies suggest that enhanced noradrenergic neurotransmission promotes
      functional recovery following cerebral lesions. The present study investigated
      whether systemic administration of an alpha(2)-adrenergic antagonist,
      atipamezole, facilitates recovery following transient focal cerebral ischemia in
      rats. The effect of atipamezole therapy on recovery from ischemia was compared
      with the effect of enriched-environment housing in rats. Ischemia was induced by
      occlusion of the right middle cerebral artery (MCA) for 120 min using the
      intraluminal filament model. Daily atipamezole treatment (1 mg/kg,
      subcutaneously) was started on day 2 after ischemia induction and drug
      administration stopped after 10 days. Another group of rats was housed in an
      enriched environment from day 2 following ischemia induction until the end of the
      experiment. Several different behavioral tests were used to measure functional
      recovery during the 26 days following the induction of focal cerebral ischemia.
      There was improved performance in the limb-placing test from the beginning of
      atipamezole treatment to day 8, and in wheel-running in the foot-slip test on
      days 2 and 4. Enriched-environment housing facilitated recovery in the foot-slip
      test in a later phase of the test period (days 8 to 10). Discovery of a hidden
      platform in a water-maze task was also facilitated in rats housed in the enriched
      environment, but this was probably due to the increased swimming speed of these
      rats. The present data suggest that the alpha(2)-adrenergic antagonist,
      atipamezole, facilitates sensorimotor recovery after focal ischemia, but has no
      effect on subsequent water-maze tests assessing spatial learning and memory, when
      assessed 11 days after the cessation of drug administration.

PMID- 11249971
TI  - Potentiation of cholinergic transmission in the rat hippocampus by angiotensin IV
      and LVV-hemorphin-7.
AB  - Recent evidence demonstrates that the fragment of angiotensin II, angiotensin II
      (3-8) termed angiotensin IV, binds with high affinity to a specific binding site,
      the AT(4) receptor. Intracerebroventricular injection of AT(4) receptor agonists
      improves the performance of rats in passive avoidance and spatial learning
      paradigms. AT(4) receptors and cholinergic neurons are closely associated in
      regions involved in cognitive processing, such as the hippocampus and neocortex.
      We therefore postulated that AT(4) receptors affect cognitive processing by
      modulating cholinergic neurotransmission. To test this, we examined the effect of
      AT(4) receptor ligands, angiotensin IV and LVV-hemorphin-7, on potassium-evoked
      [(3)H]acetylcholine ([(3)H]ACh) release from rat hippocampal slices. Hippocampal
      slices from male Sprague--Dawley rats were incubated with [(3)H]choline chloride,
      perfused with Krebs--Henseleit solution and [(3)H]ACh release was determined.
      Angiotensin IV and LVV-hemorphin-7 both potentiated depolarisation-induced
      [(3)H]ACh release from the rat hippocampus in a concentration-dependent manner
      with the maximal dose (10(-7)M) of each inducing an increase of 45+/-7.5%
      (P<0.01) and 95.8+/-19% (P<0.01) above control, respectively. Potentiation of
      release by both agonists was attenuated by the AT(4) receptor antagonist,
      divalinal-Ang IV. Angiotensin IV-induced potentiation was not affected by AT(1)
      and AT(2) receptor antagonists. These results indicate that stimulation of AT(4)
      receptors can potentiate depolarisation-induced release of ACh from hippocampal
      slices and suggest that potentiation of cholinergic transmission may be a
      mechanism by which AT(4) receptor ligands enhance cognition.

PMID- 11249970
TI  - Effects of short- and long-term exposure to c-AMP and c-GMP on the noradrenaline
      transporter.
AB  - The effects of short- and long-term exposure of cells to elevated cyclic
      adenosine monophosphate (c-AMP), using dibutyryl-c-AMP, 8-bromo-c-AMP, cholera
      toxin or forskolin, or cyclic guanosine monophosphate (c-GMP), using dibutyryl-c
      GMP or 8-bromo-c-GMP, on the activity and expression of the noradrenaline
      transporter (NAT) were examined. Short- or long-term c-GMP elevation had no
      effects on (3)H-noradrenaline uptake by rat PC12 phaeochromocytoma cells or human
      SK-N-SH-SY5Y neuroblastoma cells. Short-term c-AMP elevation (for 17 min
      experiment duration) caused a decrease in (3)H-noradrenaline uptake by PC12
      cells, but had no effects on SK-N-SH-SY5Y cells or COS-7 cells transfected with
      human or rat NAT cDNA. c-AMP did not affect (3)H-nisoxetine binding to PC12
      cells. Long-term (24 h) exposure to elevated c-AMP levels caused a decrease in
      (3)H-noradrenaline uptake and NAT mRNA in PC12 cells, but had no effects on SK-N
      SH-SY5Y cells and caused a small increase in (3)H-noradrenaline uptake in COS-7
      cells heterologously expressing rat or human NAT. Hence, c-AMP, but not c-GMP,
      causes a cell type-dependent reduction in NAT activity after short-term exposure
      and a reduction in NAT expression after long-term exposure.

PMID- 11249972
TI  - Dopaminergic effects of histamine administration in the nucleus accumbens and the
      impact of H1-receptor blockade.
AB  - The mesolimbic dopamine system is thought to play a critical role in reward
      related processes. A number of studies have shown that lesion or inhibition of
      histaminergic neurons acting through H1 receptors can potentiate the effects of
      drug-induced reward (e.g., psychostimulants and opioids) and can enhance the
      reinforcing effects of electrical stimulation of the brain. Since dopamine
      transmission in the nucleus accumbens is thought to provide a crucial link in
      these histaminergic actions, we examined the effects of local histamine
      application (0.1, 1.0 and 10.0 micromol/l) on dopamine and its metabolites in the
      nucleus accumbens of anesthetized rats by means of unilateral reverse dialysis.
      To study the influence of H1 receptors, we also applied the H1-receptor
      antagonist pyrilamine (10.0 and 20.0 mg/kg, intraperitoneally) 20 min before
      histamine administration (1 mmol/l). Finally, pyrilamine (0.1, 1.0 and 10.0
      micromol/l) was locally administered into the nucleus accumbens. The data show
      that histamine can enhance extracellular dopamine levels in the nucleus accumbens
      in a dose-dependent way. This increase was partially antagonized by prior
      peripheral administration of 10 mg/kg, and was completely blocked by 20 mg/kg, of
      pyrilamine. Finally, intra-accumbens administration of pyrilamine locally
      decreased dopamine and increased dihydroxyphenylacetic acid and homovanillic acid
      levels. These data are discussed with respect to the possible interactions
      between dopaminergic and histaminergic mechanisms in the mesolimbic system and
      their relation to mechanisms of reinforcement.

PMID- 11249977
TI  - Sinusitis -- overcoming bacterial resistance.
AB  - Sinusitis is a major cause of illness in the USA, and represents a substantial
      economic burden. Treatment of this condition usually involves antibiotics and,
      where there is a strong suspicion of bacterial etiology, has a high rate of
      success. Accurate diagnosis depends upon clinical assessment, but only four
      specific symptoms have been shown to be independent predictors of sinusitis.
      Other diagnostic approaches such as analysis of a microbiological sample must be
      considered in cases failing initial treatment. The main factors in choosing
      antibiotic therapy are the likely infecting pathogens, bacterial antibiotic
      resistance and antibiotics' pharmacological profiles. Accurate diagnosis and
      careful consideration when choosing therapy for sinusitis will optimise the
      chances of achieving an early cure.

PMID- 11249974
TI  - Observation option toolkit for acute otitis media.
AB  - The observation option for acute otitis media (AOM) refers to deferring
      antibiotic treatment of selected children for up to 3 days, during which time
      management is limited to analgesics and symptomatic relief. With appropriate
      follow-up complications are not increased, and clinical outcomes compare
      favorably with routine initial antibiotic therapy. Although used commonly in the
      Netherlands and certain Scandinavian countries, this approach has not gained wide
      acceptance in Europe and the United States. This article describes an evidence
      based toolkit developed by the New York Region Otitis Project for judicious use
      of the observation option. The toolkit is not intended to endorse the observation
      option as a preferred method of management, nor is it intended as a rigid
      practice guideline to supplant clinician judgement. Rather, it presents busy
      clinicians with the tools needed to implement the observation option in everyday
      patient care should they so desire.

PMID- 11249973
TI  - Activation of metabotropic glutamate receptors induces gamma frequency
      oscillations in the rat dentate gyrus in vivo.
AB  - Activation of mGluRs has previously been reported to cause beta/gamma frequency
      oscillations in CA1 hippocampal slices. The present study reveals that
      pharmacological activation of mGluRs in vivo induces dentate EEG oscillations at
      the low end of the gamma frequency range, with peak activity just below 30 Hz.

PMID- 11249978
TI  - A prospective study of foreign-body ingestion in 311 children.
AB  - OBJECTIVE: To determine the preferable management protocol of foreign body
      ingestion in pediatric patients. METHODS: All pediatric patients aged less than
      12 years who presented with suspected foreign body ingestion in a hospital
      setting over a period of 3 years were prospectively studied. The usefulness of
      symptoms and various diagnostic procedures to identify the impacted foreign
      bodies were analyzed. RESULTS: Of 311 children aged 4 months to 12 years, 115
      foreign bodies were encountered. The presentations in children aged younger than
      5 years were markedly different from the older children, who behaved more like
      adults. All sharp foreign bodies (107 cases or 93%), mostly fish bones (90.4%),
      were found in the oropharynx under direct vision using either tongue depressor
      (57%), Macintosh laryngoscope (6%), indirect laryngeal mirror (2%) or transnasal
      flexible endoscopy (28%). Coins (eight cases or 7%) were the only foreign body
      impacted at or below the level of cricopharyngeus. A plain cervical X-ray has a
      low sensitivity (15.9%) and a high specificity (99.5%) in identifying the foreign
      bodies. CONCLUSIONS: As the majority of the foreign bodies were sharp bones and
      situated in the oropharynx, a management protocol involving examination with a
      tongue depressor, transnasal laryngoscope, selective lateral soft tissue neck X
      ray, chest X-ray and watchful observation is usually adequate. Removal of these
      foreign bodies can be accomplished using a tongue depressor and Macintosh
      laryngoscope. Patients with a suspected coin ingestion have to be evaluated by X
      ray, and a rigid pharyngo-oesophagoscopy should be the mainstay of treatment.

PMID- 11249976
TI  - Primary cricotracheal resection in children: indications, technique and outcome.
AB  - OBJECTIVE: Treatment of subglottic stenosis has benefited greatly from
      development of grafting techniques such as larygontracheoplasty. Meanwhile,
      cricotracheal resection of the stenotic area and a major part of the cricoid
      cartilage have been shown to give excellent results in adults. PATIENTS AND
      METHODS: From June 1993 to June 2000, we performed cricotracheal resection, as
      the primary surgical procedure, for acquired (n=13), congenital (n=2) or mixed
      (n=l) subglottic stenosis in 16 pediatric patients comprising seven boys and nine
      girls. At the time of surgery, the mean weight was 16 kg and the mean age was 5
      years. Degree of stenosis was classified as grade II in one case, grade III in
      12, and grade IV in three. Eight patients underwent two-stage procedures with
      postoperative tracheostomy. A rolled reinforced silastic stent was placed for a
      mean period of 20 days and the tracheostomy tube was removed within a mean period
      of 44 days after stent removal. Eight patients underwent single-stage procedures.
      The Portex endotracheal tube was used for a mean period of 4 days. RESULTS: All
      patients underwent regular clinical and endoscopic postoperative examination.
      Mean follow-up was 38 months. No interference with laryngotracheal growth has
      been noted in any case, including the five with follow-ups longer than 5 years.
      CONCLUSIONS: The indications for laryngotracheoplasty and cricotracheal resection
      in children with subglottic stenosis are still unclear. Decisions must be made on
      a case-by-case basis. In this article the authors discuss decisional factors in
      terms of clinical findings, surgical techniques, potential complications, and
      outcome.

PMID- 11249975
TI  - Detection of Epstein-Barr virus in tonsillar tissue of children and the
      relationship with recurrent tonsillitis.
AB  - Recurrent tonsillitis has been the subject of much investigation. Events
      considered to predispose to or cause recurrent tonsillitis (RT) include the
      misuse of antibiotic therapy in acute bouts, alterations in the microflora,
      structural changes in crypt epithelium and certain viral infections. Epstein-Barr
      Virus (EBV) infection usually occurs in early childhood and can persist in
      palatine tonsil lymphocytes to induce tonsillitis at a later date. We have
      examined the presence of EBV in palatine tonsils in order to assess the
      relationship between this virus and recurrent acute tonsillitis. Tonsils were
      obtained from 85 patients, 2--14 years old (mean 5.6 years old) who underwent
      tonsils and adenoid (T&A) removal because of recurrent tonsillitis (RT) or T&A
      hypertrophy (TH). Tissues specimens were processed for non-isotopic in situ
      hybridization (ISH) using EBER 1/2 oligonucleotides (EBER RNA). The indications
      for surgery were RT in 42 patients and TH in 43 patients. In 25 out of 85 cases
      (29.4%) a positive EBER RNA reaction (15 RT and 33 TH) was found. The chi(2)-test
      showed no statistically significant difference in frequency of positive results
      between RT and TH group. We conclude that tonsils of children can be colonized by
      EBV and that the virus may be implicated in RT and TH.

PMID- 11249979
TI  - Comparison of amoxicillin and azithromycin in the prevention of recurrent acute
      otitis media.
AB  - OBJECTIVE: To compare the outcome of patients with recurrent acute otitis media
      (AOM) treated either with amoxicillin or with azithromycin. METHODS: This
      prospective, controlled, and randomized study, compares the outcome of 71
      patients with recurrent AOM treated with azithromycin (31 patients) or
      amoxicillin (40 patients) for the prevention of AOM. azithromycin was given at a
      dose of 10 mg/kg once a week, whereas amoxicillin was administered daily as a
      single intake of one third of the therapeutic dosage (20 mg/kg per day). All
      treatments were prescribed for 3 months. Both groups were homogeneous with regard
      to the currently accepted predisposing factors of recurrent AOM. Mean age of
      children was 35.3 months, and average follow-up was 11.5 months. The treatment
      was considered effective when the number of episodes of AOM dropped to less than
      50% after the prophylaxis. RESULTS: Patients in the azithromycin group had a
      clinical response to prophylaxis (80.6%) comparable to those treated with
      amoxicillin (89.5%) (P=0.300). The incidence of adverse effects was similar in
      both groups. CONCLUSION: According to these results, a prophylaxis with
      azithromycin is as useful as amoxicillin to prevent recurrent AOM.

PMID- 11249980
TI  - Indirect costs, cost-utility variations and the funding of paediatric cochlear
      implantation.
AB  - OBJECTIVE: To demonstrate the existence of variations in cost-utility associated
      with indirect costs in paediatric cochlear implantation; to illustrate the
      implications of this for purchasing decisions and; to posit a potential solution
      to anomalies in purchasing that may otherwise result when services are publicly
      funded. METHODS: Data was taken from published sources on the cost of
      implantation, outcomes measured in terms of quality adjusted life years (QALY)
      and in savings in education costs associated with paediatric cochlear
      implantation. Cost-utility ratios across education authorities were calculated
      using a single centre's implantation costs. RESULTS: Variations in savings across
      education authorities show that the cost per QALY gain associated with paediatric
      cochlear implantation can vary between approximately $12,000 and $18,000 assuming
      an exchange rate of $1.45 = 1 pound sterling for the same implant centre. These
      variations have the potential to produce situations in which less efficient
      implant centres are preferred by purchasers over more efficient ones or in which
      candidates with poorer outcomes are selected for funding over candidates with
      superior outcomes. It is important that savings associated with education be
      taken into consideration in evaluations intended to inform purchasing decisions
      regarding implantation. Equally it is important that potentially anomalous
      decisions be avoided if evaluations are to remain credible. It is argued that
      this may be achievable if public funding for implantation is determined at a
      national level and ring-fenced i.e. devoted exclusively to use in cochlear
      implantation.

PMID- 11249981
TI  - Optimizing effectiveness of laser tympanic membrane fenestration in chronic
      otitis media with effusion. Clinical and technical considerations.
AB  - OBJECTIVE: To describe the patient, disease and clinical characteristics that
      optimize the effectiveness of laser tympanic membrane fenestration (LTMF) to
      treat chronic otitis media with effusion (OME). SETTING: Four pediatric
      otolaryngology tertiary referral centers. IRB approved; participation by informed
      consent. METHODS: An observational clinical effectiveness trial was conducted in
      164 ears (94 children), who had chronic OME. All patients were candidates for
      insertion of pressure equalization tubes (PETs) but agreed to undergo LTMF
      instead. Clinical and audiologic follow-up are reported at 90 days after LTMF.
      OUTCOME MEASURES: Clinical effectiveness was defined as an effusion free middle
      ear at otoscopy with A or C1 tympanogram and normal hearing. RESULTS: At 90 days,
      66% of the 95 evaluable ears were effusion free, all with normal hearing.
      Children younger than 4 years (P<0.04), who had shorter durations of effusion
      (P<0.009), and who experienced longer duration of fenestration patency (FP)
      (P<0.009) correlated to improved outcomes. CONCLUSIONS: The use of LTMF to create
      2--3 weeks of middle ear ventilation in patients with chronic OME (middle ear
      effusion (MEE) for 3 months or greater) is effective in 66% of 95 (58%) of ears
      evaluable at 90 days follow-up. This study provides basic information needed to
      optimize the use of LTMF today and enhance research efforts in the future.

PMID- 11249982
TI  - Reappraisal of probing of the congenital obstruction of the nasolacrimal system:
      is nasal endoscopy essential?
AB  - OBJECTIVE: The rate of false passages during probing for congenital nasolacrimal
      system obstruction (CNLO) is a major limiting factor for a successful outcome.
      This shortcoming may be decreased with the use of a nasal endoscope during
      probing. This approach is particularly important in the probing training of
      ophthalmology residents. METHODS: An experienced pediatric ophthalmologist
      performed probings on 11 eyes, and a group of ophthalmology residents under his
      supervision performed probings on another 11 eyes for CNLO. Their claims of a
      successful or unsuccessful procedure were evaluated with nasal endoscopy by an
      ear--nose--throat (ENT) surgeon. The age range of the patients was 8-23 months.
      RESULTS: The ophthalmologist made two false passages, one of which he was aware,
      out of 11 eyes. The residents had five false passages, two of which were unclear
      to them, out of another 11 eyes. No false passages occurred in obstructions at
      the level of the Hasner valve. None of the successful probings required more than
      a 30 mm probe introduction into the nasolacrimal canal from the inferior punctum.
      CONCLUSION: It seems justified to have a nasal endoscopic evaluation, performed
      by an ENT surgeon, for probings during the training program of ophthalmology
      residents. Difficult cases with stenosis proximal to the inferior meatus, prior
      false passage experience on a particular case, and any indication for silicone
      tube implantation will benefit from the use of an endoscope during the procedure.
      In order to achieve the best results in CNLO, the collaborative teamwork of an
      ophthalmologist and an ENT specialist is necessary.

PMID- 11249984
TI  - Utilization of bone-anchored hearing aids in children.
AB  - OBJECTIVE: Bone-anchored hearing aids (BAHAs) are indicated for use in children
      with bilateral microtia or chronic suppurative otitis media, which precludes the
      use of conventional hearing aids. METHODS: Nineteen consecutive children using
      BAHAs were reviewed retrospectively. Outcome measures included the long-term
      stability of BAHAs, frequency of adverse dermatological reactions at the implant
      site, and audiologic thresholds. RESULTS: Osseointegration was achieved in 95% of
      patients. One patient lost the implant fixture secondary to direct head trauma.
      Site revisions were required for only two patients secondary to soft-tissue
      overgrowth at the abutment site. There were no differences between pre
      implantation and post-implantation bone or air conduction thresholds, but there
      was a statistical improvement in the post-implantation aided thresholds.
      CONCLUSIONS: Utilization of paediatric BAHAs, in a distinct population, is a
      reliable and successful method for audiologic rehabilitation.

PMID- 11249983
TI  - Bacteremia during tonsillectomy.
AB  - OBJECTIVE: To investigate bacteremia in patients who underwent tonsillectomy with
      a dissection method due to chronic tonsillitis, which may lead to dramatic
      results in patients that have a cardiovascular infection risk. In this study, it
      was explored whether the tonsil surface and the tonsil tissue interior
      microorganisms are different or not, and whether these microorganisms carry
      bacteremia development risk. METHODS: Forty patients were enrolled in the study
      in ENT Clinic, Firat University. A bacteriological research was performed on
      patients with no treatment with antibiotics for a month before the operation.
      Tonsil surface and deep tissue cultures were performed, and venous blood samples
      were taken for cultures before and after the operation. RESULTS: Surface and deep
      tissue cultures of tonsils of the cases represented a different result in 27.5%
      of the patients. No reproduction was observed regarding the blood cultures taken
      before tonsillectomy. Bacteremia was found in blood samples of ten patients (25%)
      taken immediately after tonsillectomy. CONCLUSION: Hence, it has been concluded
      that different microorganisms may be present among the tonsil surface and tonsil
      deep tissue cultures and that bacteremia may develop after tonsillectomy.
      Therefore, to prevent the possible dramatic outcomes after tonsillectomy the
      required measures during the preoperative period should be taken into
      consideration, especially in patients that have chronic tonsillitis with
      cardiovascular disease.

PMID- 11249986
TI  - Sphenochoanal polyp: endoscopic surgery.
AB  - Sphenochoanal polyp is a rare entity originating from sphenoid sinus. It may be
      confused with antrochoanal polyp on anterior rhinoscopy because of its similar
      appearance. Computerized tomography and nasal endoscopy have contributed to an
      increase of accuracy in the diagnosis of these masses. Simple polypectomy that
      leaves some part of the polyp inside the sphenoid sinus carries a high risk of
      recurrence. Destructive external approaches to gain access to the sphenoid sinus
      are also not advisable in children for a benign disease. We present two cases of
      sphenochoanal polyps in two children that were operated by endonasal endoscopic
      approach. They were free of symptoms after surgery. No complications and
      recurrences were observed at 28 and 18 months of follow-up periods respectively.

PMID- 11249985
TI  - Bilateral choanal atresia associated with nasal dermoid cyst and sinus: a case
      report and review of the literature.
AB  - The relationship of choanal atresia to various systemic malformations is well
      acknowledged by the CHARGE acronym: colobomas, heart defects, atresia choanae,
      retarded growth and development, genito-urinary defects, and ear defects. In the
      past, we have reported the finding of an isolated skull base malformation
      associated with choanal atresia. We report here a unique case of choanal atresia
      associated with a patent foramen cecum and intracranial extension of a dermoid
      sinus. The embryogenesis of this condition is accounted for by the mesodermal
      flow theory of choanal atresia formation, and implies a need for thorough imaging
      of the anterior skull base in cases of bilateral atresia.

PMID- 11249987
TI  - A case of nasal glioma in a new-born infant.
AB  - We report a 1 day old girl with a nasal mass that was diagnosed as an intranasal
      glioma. The tumor mass was noted to be localized laterally from, and based along,
      the inferior turbinate. Nasal glioma is a developmental abnormality of neurogenic
      origin with no malignant potential. An intranasal mass requires careful
      rhinological, neurological and radiological examinations. With adequate initial
      removal, excisional biopsy usually allows complete recovery. A frontal craniotomy
      approach is preferred for those patients who have nasal glioma with an
      intracranial connection. With no evidence of an intracranial connection, a
      conservative extracranial approach is recommended.

PMID- 11249988
TI  - From odor and pheromone transduction to the organization of the sense of smell.
AB  - Chemosensory neurons in the mammalian nose detect an array of odors and
      pheromones that carry essential information about the animal's environment. How
      the nose organizes this immense amount of information is a major question in
      sensory biology. New evidence suggests that there are several subpopulations of
      sensory neurons in the nose that project to different areas in the forebrain.
      Strikingly, evidence is now emerging that several of these neuronal
      subpopulations employ distinct second messenger cascades to transduce chemical
      stimuli. This new understanding of the heterogeneity of chemosensory transduction
      mechanisms offers the opportunity to use genetically altered animals to
      specifically target these subpopulations. Such approaches should enable
      researchers to examine the role that each of these subsystems could play in
      chemosensory-dependent behaviors.

PMID- 11249990
TI  - Resolving the Heuser-Ceccarelli debate.
AB  - Nearly 30 years ago, a debate over two disparate models of synaptic vesicle
      retrieval arose. Subsequent investigations to determine which model was correct
      proved inconclusive and served only to further the debate. However, recent
      evidence has begun to suggest that both models are valid and relevant in
      understanding the complex nature of vesicle recycling.

PMID- 11249989
TI  - Lipoprotein receptors: beacons to neurons?
AB  - Lipoprotein receptors were originally considered simply as cellular transporters
      for cholesterol and other lipids. This view is rapidly changing. Signaling
      functions have recently been recognized in several members of the low-density
      lipoprotein receptor gene family. These Apolipoprotein E receptors are highly
      expressed in the developing and in the mature nervous system, in which they
      regulate crucial developmental processes and might also participate in synaptic
      neurotransmission.

PMID- 11249991
TI  - Is LTP good or bad for memory?

PMID- 11249992
TI  - Alzheimer's disease: beta-amyloid hypothesis strengthened!

PMID- 11249995
TI  - Britain's [correction of Britian's] embryo cloning law passed.

PMID- 11249993
TI  - It's enough to raise your blood pressure!

PMID- 11250000
TI  - Nobel objections.

PMID- 11250003
TI  - Ideal homes? Housing effects on rodent brain and behaviour.
AB  - Rodents used in biomedical research are typically reared in small cages that lack
      key features of their natural habitats. These conditions impose constraints on
      behaviour and brain development, resulting in altered brain functions. In this
      article, evidence for three different ways in which barren housing conditions
      interfere with brain development and behaviour is reviewed. Early environmental
      deprivation, thwarting of behavioral response rules, and disruption of habitat
      dependent adaptation processes are shown to result in aberrant or maladaptive
      brain functions. Current standard housing conditions could therefore compromise
      the utility of rodents for research, especially in behavioural neuroscience.
      However, a better understanding of the animals' needs and of the environmental
      factors involved in the control of behaviour could offer a biological basis for
      refinement.

PMID- 11250004
TI  - Nitric oxide: a novel link between synaptic and nonsynaptic transmission.
AB  - Accumulating evidence indicates that nitric oxide (NO) inhibits the function of
      monoamine transporters. Because the production of NO by neuronal NO synthase
      (nNOS) is closely related to the activation of NMDA receptors, the level of NO
      around nNOS-containing synapses reflects the activity of glutamate-mediated
      neurotransmission. Glutamate participates mainly in synaptic interactions, but
      with the help of NO, the strength of excitatory input might be nonsynaptically
      signaled to the surrounding monoaminergic neurons, which can adapt to the changes
      without receiving glutamatergic input and without synthesizing glutamate
      receptors. Thus, the effect of NO on transporters represents a new form of
      interneuronal communication, a nonsynaptic interaction without receptors.

PMID- 11250005
TI  - RNAi and brain function: was McConnell on the right track?
AB  - RNA interference (RNAi), one of the hottest topics of molecular biology research
      today, has unique features that are eerily reminiscent of the phenomenon of "RNA
      mediated memory transfer," a controversial line of work that was investigated
      with great enthusiasm in the 1960s. If not a coincidence, then this suggests
      taking a new look at RNA-mediated modulation of neural function and raises the
      possibility that RNAi might be one of the physiologic mechanisms that regulate
      long-term gene expression in the brain.

PMID- 11250006
TI  - Targeting small Abeta oligomers: the solution to an Alzheimer's disease
      conundrum?
AB  - Amyloid beta (Abeta) is a small self-aggregating peptide produced at low levels
      by normal brain metabolism. In Alzheimer's disease (AD), self-aggregation of
      Abeta becomes rampant, manifested most strikingly as the amyloid fibrils of
      senile plaques. Because fibrils can kill neurons in culture, it has been argued
      that fibrils initiate the neurodegenerative cascades of AD. An emerging and
      different view, however, is that fibrils are not the only toxic form of Abeta,
      and perhaps not the neurotoxin that is most relevant to AD: small oligomers and
      protofibrils also have potent neurological activity. Immuno-neutralization of
      soluble Abeta-derived toxins might be the key to optimizing AD vaccines that are
      now on the horizon.

PMID- 11250007
TI  - The link between excitotoxic oligodendroglial death and demyelinating diseases.
AB  - Oligodendrocytes, the myelinating cells of CNS axons, are highly vulnerable to
      excitotoxic signals mediated by glutamate receptors of the AMPA and kainate
      classes. Receptors in these cells are commonly activated by glutamate that is
      released from axons and glial cells. In addition, oligodendrocytes contribute to
      the control of extracellular glutamate levels by means of their own transporters.
      However, acute and chronic alterations in glutamate homeostasis can result in
      overactivation of AMPA and kainate receptors and subsequent excitotoxic
      oligodendroglial death. Furthermore, demyelinating lesions caused by excitotoxins
      can be similar to those observed in multiple sclerosis. This, together with the
      effect of AMPA and kainate receptor antagonists in ameliorating the neurological
      score of animals with experimental autoimmune encephalomyelitis (an animal model
      of multiple sclerosis), indicates that oligodendrocyte excitotoxicity could be
      involved in the pathogenesis of demyelinating disorders.

PMID- 11250008
TI  - Novel neurotransmitters as natural ligands of orphan G-protein-coupled receptors.
AB  - The "orphan" G-protein-coupled receptors (GPCRs) are cloned GPCRs that bind
      unknown ligands. Since 1995, nineteen orphan GPCRs have been used as targets to
      identify and isolate their natural ligands via the application of the "orphan
      receptor strategy". These ligands are peptides, lipids or biogenic amines, and
      act as transmitter molecules. One nucleotide-sugar derivative and six peptides or
      peptide families identified through this strategy are novel and have already
      enriched our understanding of various brain functions.

PMID- 11250029
TI  - To charge or not to charge?
AB  - The ability to engineer proteins with increased thermostability will profoundly
      broaden their practical applications. Recent experimental results show that
      optimization of charge-charge interactions on the surface of proteins can be a
      useful strategy in the design of thermostable enzymes. Results also indicate a
      possibility that such optimized interactions provide structural determinants for
      enhanced stability of proteins from thermophilic organisms. In this article, the
      general strategy for design of thermostable proteins and perspectives for future
      studies are discussed.

PMID- 11250030
TI  - Green biotechnology and European competitiveness.
AB  - Europe has led many aspects of gene research and yet it has been unable to
      translate these discoveries into a globally dominant industrial sector. There are
      valid societal, political and financial reasons for its reluctance to deploy
      agricultural biotechnology but this reluctance might have unintended
      consequences. It will be hard to de-commoditize agriculture and improve farmer's
      lives. Research in medical biotechnology and the global environment might suffer.
      Europe could damage its overall economy and its global competitive standing.

PMID- 11250009
TI  - Sleep and memory: a molecular perspective.
AB  - This review synthesizes data from behavioral studies examining the role of sleep
      in memory storage with what is known about the molecular mechanisms of memory
      consolidation. There are striking similarities in the effects on memory storage
      of post-training pharmacological manipulations and post-training manipulations of
      sleep. For example, inhibition of protein synthesis is most effective if it
      occurs at a time post-training when rapid eye movement (REM) sleep is required
      for memory consolidation. The neurochemical changes that occur across sleep/wake
      states, especially the cholinergic changes that occur in the hippocampus during
      REM sleep, might provide a mechanism by which sleep modulates specific cellular
      signaling pathways involved in hippocampus-dependent memory storage.

PMID- 11250031
TI  - Proton pumps: mechanism of action and applications.
AB  - Recent progress in understanding the molecular structures and mechanisms of
      action of proton pumps has paved the way to their novel applications in
      biotechnology. Proton pumps, bacteriorhodopsin and ATP synthases in particular,
      are capable of continuous, renewable conversion of light to chemical, mechanical
      or electrical energy, which can be used in macro- or nano-scale devices. The
      capability of protein systems incorporated into liposomes to generate ATP, which
      can be used to drive chemical reactions and to act as molecular motors has been
      already demonstrated. Other possible applications of such biochemical devices
      include targeted drug delivery and biocatalytic reactors. All these devices might
      prove superior to their inorganic alternatives.

PMID- 11250032
TI  - 3D modelling of gene expression patterns.
AB  - The current genome-sequencing projects provide "word indices" of the book of
      life. A central post-genomic question will be how these words are three
      dimensionally deployed in the generation of organism form. Gene expression
      studies of developing organisms contribute an increasing wealth of snapshot data
      on the activation of individual genes at selected locations and single moments in
      the developmental process. However, a comprehensive understanding of the dynamic
      activation of multiple genes and their functional role in controlling the 3D
      processes of collective cell behaviour, pattern formation and morphogenesis,
      requires special tools for a systematic description of spatio-temporal patterns
      of gene activation and the ensuing phenotypic effects. This article concentrates
      on new, computer-based tools for the 3D analysis of gene expression patterns in
      embryonic development and their use for the systematic establishment of
      comprehensive gene expression maps.

PMID- 11250033
TI  - Potential failsafe mechanisms against the spread and introgression of transgenic
      hypervirulent biocontrol fungi.
AB  - Microbial biocontrol agents are typically inefficient owing to the evolutionary
      necessity to be in balance with their hosts to survive. If transgenetically
      rendered hypervirulent, however, they could be competitive alternatives to
      pesticides. Potential means are delineated to prevent, contain or mitigate
      uncontrollable spread of hypervirulent biocontrol organisms, mutations that
      increase their host range, and the sexual or asexual introgression of
      hypervirulence genes into pathogens of other organisms. The use of asporogenic
      deletion mutants as a platform for generating transgenic hypervirulent
      biopesticides would prevent such spread. Hypervirulence genes flanked with
      available 'transgenetic mitigator' (TM) genes (genes that are neutral or positive
      to the biocontrol agent but deleterious to recombinants) would decrease virulence
      to non-target species.

PMID- 11250035
TI  - Energetics of overall metabolic reactions of thermophilic and hyperthermophilic
      Archaea and bacteria.
AB  - Thermophilic and hyperthermophilic Archaea and Bacteria have been isolated from
      marine hydrothermal systems, heated sediments, continental solfataras, hot
      springs, water heaters, and industrial waste. They catalyze a tremendous array of
      widely varying metabolic processes. As determined in the laboratory, electron
      donors in thermophilic and hyperthermophilic microbial redox reactions include
      H2, Fe(2+), H2S, S, S2O3(2-), S4O6(2-), sulfide minerals, CH4, various mono-, di
      , and hydroxy-carboxylic acids, alcohols, amino acids, and complex organic
      substrates; electron acceptors include O2, Fe(3+), CO2, CO, NO3(-), NO2(-), NO,
      N2O, SO4(2-), SO3(2-), S2O3(2-), and S. Although many assimilatory and
      dissimilatory metabolic reactions have been identified for these groups of
      microorganisms, little attention has been paid to the energetics of these
      reactions. In this review, standard molal Gibbs free energies (DeltaGr(0)) as a
      function of temperature to 200 degrees C are tabulated for 370 organic and
      inorganic redox, disproportionation, dissociation, hydrolysis, and solubility
      reactions directly or indirectly involved in microbial metabolism. To calculate
      values of DeltaGr(0) for these and countless other reactions, the apparent
      standard molal Gibbs free energies of formation (DeltaG(0)) at temperatures to
      200 degrees C are given for 307 solids, liquids, gases, and aqueous solutes. It
      is shown that values of DeltaGr(0) for many microbially mediated reactions are
      highly temperature dependent, and that adopting values determined at 25 degrees C
      for systems at elevated temperatures introduces significant and unnecessary
      errors. The metabolic processes considered here involve compounds that belong to
      the following chemical systems: H-O, H-O-N, H-O-S, H-O-N-S, H-O-C(inorganic), H-O
      C, H-O-N-C, H-O-S-C, H-O-N-S-C(amino acids), H-O-S-C-metals/minerals, and H-O-P.
      For four metabolic reactions of particular interest in thermophily and
      hyperthermophily (knallgas reaction, anaerobic sulfur and nitrate reduction, and
      autotrophic methanogenesis), values of the overall Gibbs free energy (DeltaGr) as
      a function of temperature are calculated for a wide range of chemical
      compositions likely to be present in near-surface and deep hydrothermal and
      geothermal systems.

PMID- 11250034
TI  - The archaeal flagellum: a different kind of prokaryotic motility structure.
AB  - The archaeal flagellum is a unique motility apparatus distinct in composition and
      likely in assembly from the bacterial flagellum. Gene families comprised of
      multiple flagellin genes co-transcribed with a number of conserved, archaeal
      specific accessory genes have been identified in several archaea. However, no
      homologues of any bacterial genes involved in flagella structure have yet been
      identified in any archaeon, including those archaea in which the complete genome
      sequence has been published. Archaeal flagellins possess a highly conserved
      hydrophobic N-terminal sequence that is similar to that of type IV pilins and
      clearly unlike that of bacterial flagellins. Also unlike bacterial flagellins but
      similar to type IV pilins, archaeal flagellins are initially synthesized with a
      short leader peptide that is cleaved by a membrane-located peptidase. With recent
      advances in genetic transfer systems in archaea, knockouts have been reported in
      several genes involved in flagellation in different archaea. In addition,
      techniques to isolate flagella with attached hook and anchoring structures have
      been developed. Analysis of these preparations is under way to identify minor
      structural components of archaeal flagella. This and the continued isolation and
      characterization of flagella mutants should lead to significant advances in our
      knowledge of the composition and assembly of archaeal flagella.

PMID- 11250036
TI  - Virulence genes in the pathogenic yeast Candida albicans.
AB  - In recent years, the incidence of fungal infections has been rising all over the
      world. Although the amount of research in the field of pathogenic fungi has also
      increased, there is still a need for the identification of reliable determinants
      of virulence. In this review, we focus on identified Candida albicans genes whose
      deletant strains have been tested in experimental virulence assays. We discuss
      the putative relationship of these genes to virulence and also outline the use of
      new different systems to examine the precise effect in virulence of different
      genes.

PMID- 11250037
TI  - Pregnancy can induce long-persisting primed CTLs specific for inherited paternal
      HLA antigens.
AB  - Previous studies showed that pregnancy can prime the maternal cellular immune
      response directed against paternal HLA antigens. Primed CTLs specific for
      inherited paternal HLA antigens (IPA) were found in women who had formed HLA allo
      antibodies, whereas naive CTLs were present in women who did not form antibodies
      against the paternal HLA antigens. As HLA allo antibodies may disappear in time,
      it is not clear which women on the waiting list for transplantation have been
      sensitized to paternal HLA antigens and are at risk for graft rejection if
      paternal HLA antigens are shared by the donor organ. The presence of primed CTLs
      specific for a particular antigen is considered to be a reflection of
      sensitization.In the present study we investigated whether these primed CTLs
      persist in women who had been pregnant and had formed antibodies against the
      inherited paternal HLA class I antigens. For this purpose 14 women who had their
      last pregnancy 10 years ago were analyzed with respect to IPA-specific CTLp
      frequencies and the presence of high avidity CTLs directed against inherited
      paternal HLA class I antigens. Although primed CTLs specific for IPA's were found
      more frequently in women with persisting alloantibodies, they still can be
      detected when the antibodies have disappeared. The current data show that primed
      CTLs directed against inherited paternal HLA antigens towards which antibodies
      have been formed in the past can persist for more than 10 years after pregnancy.
      The cellular test used in our study can be useful to detect presensitization in
      women with a history of pregnancy, who enter the waiting list for
      transplantation.

PMID- 11250038
TI  - Changes in dendritic cell subsets in the lymph nodes of rhesus macaques after
      application of glucocorticoids.
AB  - Corticosteroids are used therapeutically as potent immunosuppressive and
      antiinflammatory drugs for a broad spectrum of diseases. Although corticosteroids
      are known to inhibit the production of many cytokines in activated T cells, there
      is also evidence for increases in IL-4 and in some cases IFNgamma production.
      These conflicting results may be caused by contrary effects of corticosteroids on
      different cell types involved in immune regulation, for instance antigen
      presenting cells (APC) versus T cells. In the present study we simultaneously
      investigated the effect of local as well as systemic application of
      glucocorticoids (GCC) on the phenotype of APC in the skin as well as the lymph
      nodes in a model primate species, the rhesus macaque. Using a range of APC
      markers, including CD68, HAM56, HLA-DR, CD1a, p55, RFD-1, and costimulatory
      molecules CD40, CD80, and CD86 we document the close phenotypic resemblance of
      rhesus and human APC. We noted that topical GCC treatment specifically lead to a
      marked decrease in the number of CD1a expressing cells in the draining lymph
      nodes. However, the number of CD1a positive cells in peripheral lymph nodes was
      not affected by systemic GCC treatment. Importantly, by performing double
      staining of CD1a with RFD-1 we observed a shift in the expression pattern of
      these dendritic cell markers in the lymph nodes, with an increase in the number
      of RFD-1 single positive cells relative to CD1a single positive and CD1a/RFD-1
      double positive cells. These findings suggest that GCC treatment results in the
      presence of phenotypically more mature APC.

PMID- 11250040
TI  - Characterization of HLA class I specific antibodies by ELISA using solubilized
      antigen targets: I. Evaluation of the GTI QuikID assay and analysis of antibody
      patterns.
AB  - The development of solid phase immunoassays using solubilized HLA molecules as
      targets has provided a means of detecting HLA-specific antibodies that overcomes
      many of the shortcomings of lymphocyte based assays. We have evaluated a
      commercially available assay, the GTI QuikID (QID), that uses solubilized class I
      molecules from 40 subjects selected for their HLA phenotype, to characterize HLA
      specific antibodies. We tested 595 sera from 319 subjects and compared the
      results obtained with QID to those obtained with cytotoxicity (CYT) and with GTI
      QuikScreen (QS) as well as to historic data. The correlation of QID with CYT (r =
      0.54) was comparable to that between QID and QS (r = 0.60). The majority of
      disparities between QS and QID were apparent false negatives with QID that could
      be overcome by analyzing QID data at lower cutoff values. In contrast, most of
      the disparities between QID and CYT were false negatives in CYT due to the
      relatively low sensitivity of that assay. As expected, the ELISA was more
      sensitive (97%) than CYT (78%) but had a somewhat lower specificity (87% vs. 92%)
      due, most likely, to selection of sera that excluded most sera that were known to
      be nonspecific by CYT. Determination of antibody specificity could be achieved
      quickly by manual analysis of the QID data because of the way the data are
      presented by the manufacturer's software. Interestingly, the frequencies of
      different antibodies detected by ELISA differed from those detected by CYT with
      ELISA identifying more sera containing antibodies to both A and B locus antigens.

PMID- 11250039
TI  - Human polyspecific immunoglobulin for therapeutic use induces p21/WAF-1 and Bcl
      2, which may be responsible for G1 arrest and long-term survival.
AB  - High-dose intravenous immunoglobulin (IVIg) is used as therapy in an increasing
      number of immune mediated disorders including infections and autoimmune
      conditions. IVIg exerts profound effects both in vivo as well as in vitro on
      humoral and cell-mediated immunity. In this study we investigated whether IVIg
      could alter the pattern of apoptosis and apoptosis related proteins including Bcl
      2, Bax, p53, CD95, and p21/WAF-1, a protein well known to arrest cells in G1
      phase of the cell cycle and finally proliferation marker Ki-67 on peripheral
      blood mononuclear cells (PBMC). The cells were cultured either unstimulated or
      with mitogen in the presence or absence of different IVIg preparations. A dual
      effect by IVIg was found. The incidence of apoptosis was elevated in activated Ki
      67 and CD95 positive PBMC, whereas it was lower in small, nonactivated cells. The
      cells that survived were associated with a striking increase in the expression of
      p21/WAF-1 suggesting G1 arrest. A concomitant upregulation of Bcl-2 was also
      obtained by IVIg exposition resulting in long-term survival. We suggest that
      these abilities of IVIg to alter cell cycle progression and apoptosis could
      explain some of the beneficial effects obtained in vivo with IVIg therapy.

PMID- 11250041
TI  - Characterization of HLA class I specific antibodies by ELISA using solubilized
      antigen targets: II. Clinical relevance.
AB  - Until recently, the nature of humoral sensitization to HLA has been characterized
      by data from lymphocyte-based assays, predominantly cytotoxicity tests. We have
      examined the characteristics, determined by enzyme-linked immunosorbent assay
      (ELISA), of sera from 191 subjects known to have produced HLA-specific antibody.
      We found that ELISA detected higher frequencies compared with cytotoxicity of
      many (74.5%), but not all, HLA-specific antibodies; in many cases (42.6%) the
      frequencies of these antibodies were higher than predicted from population
      frequencies whereas some antibodies (23.4%) occurred with lower than expected
      frequencies. Some of the increase in frequencies can be accounted for by
      crossreactivity, i.e., sensitization to epitopes shared among two or more allelic
      products. The presence of epitopes shared between a recipient's antigen and a
      mismatched antigen in a donor also tended to narrow the specificity of antibody
      produced. However the data also indicate differences in immunogenicity among
      different antigens suggesting that crossreactive group matching would be
      beneficial in some but not all cases. Finally, we present case studies to
      illustrate the value of ELISA in predicting humoral rejection episodes and in
      monitoring the efficacy of rejection therapies.

PMID- 11250042
TI  - Identification of ICAM-1 polymorphism that is associated with protection from
      transplant associated vasculopathy after cardiac transplantation.
AB  - Transplant associated coronary disease (TxCAD) is the main cause of late graft
      loss following cardiac transplantation. It is a multifactorial disease with
      immunologic and nonimmunologic components involved. This study was undertaken to
      analyze the gene polymorphism in adhesion molecules in donors and recipients and
      to investigate its potential association with the development of TxCAD. A total
      of 82 cardiac transplant patients, 96 donors and 101 UK controls, were genotyped
      retrospectively. Nine nucleotide polymorphisms in L-selectin, E-selectin, ICAM-1,
      and PECAM were analyzed using allele-specific PCR-SSP assay. Recipients were
      selected on the basis of the development of TxCAD: patients who had developed
      TxCAD within 2 years after transplantation, and patients who did not have TxCAD
      within 4.5-5 years after transplantation. All recipients received CyA and
      azathioprine as a primary immunosuppression. Associations were assessed by using
      Fisher's exact test. No association was found between E-selectin, L-selectin, and
      PECAM allele or genotype frequencies and TxCAD. However, the donors whose
      recipients did not develop TxCAD at first 2 years had a significant increase of
      ICAM-1 E-469 allele compared with donors, whose recipients developed TxCAD (63.8%
      vs 46.4%, p = 0.042) and to UK controls (63.8% vs 47%, p = 0.04). Moreover, we
      found that the decreased frequency of ICAM E469 allele was associated with the
      increased number of rejection episodes. The 469 E/K polymorphism is in exon 6 and
      results in a change from glutamic acid to lysine in Ig-like domain 5 of ICAM-1,
      which is thought to affect interactions with LFA-1 and adhesion of B-cells. Our
      data suggest the presence of allele E469 ICAM-1 in either donor or recipient is
      protective against allograft rejection in a transplant setting.

PMID- 11250043
TI  - TAPI polymorphisms in several human ethnic groups: characteristics, evolution,
      and genotyping strategies.
AB  - Genetic variations in the locus encoding the transporter associated with antigen
      processing, subunit 1 (TAP1), were systematically studied using samples from
      Caucasians, Africans, Brazilians, and compared with data from chimpanzees. PCR
      amplified genomic sequences corresponding to the 11 exons were analyzed by single
      strand conformation polymorphism (SSCP) and sequencing. Six nonsynonymous and 2
      synonymous single nucleotide polymorphisms (SNPs) were found to be common in one
      ethnic group or another, and they involved codons 254 (Gly-GGC/Gly-GGT) in exon
      3, 333 (Ile-ATC/Val-GTC) in exon 4, 370 (Ala-GCT/Val-GTT) in exon 5, 458 (Val
      GTG/Leu-TTG) in exon 6, 518 (Val-GTC/Ile-ATC) in exon 7, 637 (Asp-GAC/Gly-GGC),
      648 (Arg-CGA/Gln-CAA) and 661 (Pro-CCG/Pro-CCA) in exon 10. At each SNP site the
      sequence listed first was predominant in all ethnic groups. Several SNPs
      segregated on the same chromosome regardless of populations and species.
      Together, the SNPs produced 5 major human TAP1 alleles, 4 of which matched the
      officially recognized alleles *0101, *02011, *0301, and *0401; the 5th allele
      differed from each of those by at least 4 SNPs. Overall, TAP1*0101 was the
      predominant allele in all ethnic groups, with frequencies ranging from 0.667 in
      Zambians to 0.808 in US Caucasians. The TAP1*0401 frequency showed the greatest
      difference between Africans (0.221-0.254) and Caucasians (0.033), with Brazilians
      (0.058) fitting in the middle. Consistent with earlier work based on Caucasians
      and gorillas, *0101 appeared to be the newest human TAP1 allele, suggesting a
      dramatic spread of *0101 into all human populations examined. Characterization of
      TAP1 polymorphisms allowed the design of a PCR-based genotyping scheme that
      targeted 7 SNP sites and required 2 separate genotyping techniques.

PMID- 11250045
TI  - Sequence analysis of the MHC class I region reveals the basis of the genomic
      matching technique.
AB  - The genomic matching technique (GMT) improves survival following bone marrow
      transplantation (BMT) between unrelated donor and recipient pairs correlating
      with a decrease in incidence and severity of graft-versus-host disease (GvHD).
      The principles of this technique are based on the duplication and polymorphic
      characteristics of the major histocompatibility complex (MHC). Specifically, the
      beta block GMT matches for a 300 kb region that contains the human leukocyte
      antigen (HLA-B and -C) genes as well as other non-HLA genes such as the natural
      killer cell receptor ligand PERB11 (MIC). The block contains two large segmental
      duplications. One results in two PERB11 genes (11.1 and 11.2), the other in two
      class I genes (HLA-B and -C). With the complete sequencing of the class I region
      of the MHC in different haplotypes, we can now show that the beta block GMT
      profiles reflect amplification of the duplicated PERB11 segments and not the
      duplicated segments containing HLA-B and -C, and yet provide a signature that
      characterizes the entire block rather than individual loci.

PMID- 11250044
TI  - Novel alleles at the lymphotoxin alpha (LTalpha) locus mark extended HLA
      haplotypes in native Africans.
AB  - Genetic variations at the closely related tumor necrosis factor alpha (TNFalpha
      or TNF) and lymphotoxin alpha (LTalpha, formerly TNFbeta) loci have been well
      documented in various human populations, and several haplotypes spanning the MHC
      class I and class II loci are known to carry specific TNF alleles. Genotyping of
      the TNFc microsatellite within the first intron of LTalpha in 285 Rwandans and
      319 Zambians revealed two predominant alleles, c1 at frequencies of 0.598 and
      0.683 and c2 at 0.384 and 0.307, respectively. Overall, the distribution of TNFc
      genotypes containing the major alleles conformed well to the Hardy-Weinberg
      equilibrium in both cohorts. Two previously unrecognized minor TNFc alleles were
      also detected: the first, designated c0, was found in 10 native Africans and was
      the only allele present in 10 chimpanzees; the second, designated c3, was seen in
      6 other African patients. Further genotyping at loci for HLA class I, class II,
      and for transporters associated with antigen processing, subunit 1 (TAP1) in
      those 16 individuals suggested a tight, stable extended haplotype involving c0
      and 26Asn (LTalpha)-TNF3 (TNF promoter -238A and -308G)-DRB1*1503-DQB1*0602
      TAP1.2 (333Val)-TAP1.4 (637Gly). The c3 allele was observed on another extended
      haplotype with 26Thr (LTalpha)-TNF1 (TNF promoter -238G and -308G)-DQB1*0102
      DQB1*0501-TAP1*0101 (333Ile and 637Asp). The c3-tagged haplotype further extended
      to Cw*15 at the HLA class I C locus, but no specific A or B alleles could be
      unambiguously assigned. Positive associations between c2 homozygosity and HIV-1
      seronegative status in both Rwandans and Zambians (odds ratio = 2.03 and 2.00, p
      = 0.04 and 0.07, respectively) had little effect on the haplotype assignments.
      These findings suggest a preferential expansion of the human TNFc dinucleotide
      (CT/AG) repeat sequence and further imply the existence of two extended MHC
      lineages that have not been disrupted by recombinations.

PMID- 11250046
TI  - Polymorphism and distribution of HLA-DR2 alleles in Mexican populations.
AB  - DRB1*15/16 nucleotide polymorphism was analyzed in 68 DR2 positive individuals
      (18 Mexican Mestizos, 30 Mazatecans and 20 Nahuas), carrying a total of 75 DR2
      haplotypes. HLA-DR2 was one of the most frequent specificities detected in
      Mazatecans and Nahuas with gene frequency (gf) of 0.232 and 0.141, respectively.
      In these populations DRB1*16 was the most frequent DR2 split (gf = 0.183 in
      Mazatecans and gf = 0.135 in Nahuas), whereas in Mexican Mestizos the most
      frequent was DRB1*15 (gf = 0.065). Four DRB1-DQB1 combinations in Mexican
      Mestizos, two in Mazatecans and one in Nahuas were in linkage disequilibrium. In
      spite of the restricted polymorphism, there were differences on DRB1*15/16
      alleles found in Mexicans. DRB1*1501 a Caucasian allele was predominant in
      Mexican Mestizos, whereas DRB1*1602 an Amerindian allele was characteristic on
      Indian populations. An important difference was detected among the Amerindian
      populations studied since DRB1*1502 was only present in Mazatecans. This data
      corroborates the restricted polymorphism of DRB1*15/16 and the high frequency of
      DRB1*16 subtype in autochthonous American populations and suggest that the
      differences in gene frequencies of DRB1*15/16 alleles could be helpful in
      distinguishing each of these population.

PMID- 11250047
TI  - Nomenclature for factors of the HLA system, Update November 2000.

PMID- 11250048
TI  - Nomenclature for factors of the HLA system, Update December 2000.

PMID- 11250050
TI  - 109Cd accumulation in the calcified parts of rat bones.
AB  - A recent epidemiological study showed an increased risk for bone fractures after
      chronic low-level cadmium exposure. This finding agrees with those of cadmium
      accumulation in rat bones after chronic oral exposure which reduced the
      mechanical strength of the bones. There are indications that ossicular cadmium
      uptake may be higher during growth and may contribute over proportion to life
      long cadmium accumulation in the skeleton. The present study investigates this
      hypothesis in 59 male Sprague-Dawley rats. 109Cd distribution showed no
      differences after intravenous (i.v.) administration of different doses (0.02-2.00
      micromol 109Cd/kg body weight) and at different time points after injection (3
      and 10 days). Iron-deficiency had no impact on 109Cd distribution, neither during
      growth nor in adult animals. Age, however, showed an impact on cadmium
      distribution. Hepatic 109Cd accumulation was significantly higher in adult rats
      while 109Cd distribution in the bones as well as 109Cd concentration in cortical
      and trabecular bone tissue was significantly higher during growth. No difference
      in 109Cd uptake was found between femur epiphysis and diaphysis after one-dose
      i.v. application, which is in contrast to earlier results after chronic oral
      cadmium administration to rats. This difference may be explained by a different
      saturation for cadmium uptake in these two bone sections. Cadmium exposure during
      growth, thus, seems to contribute considerably to cumulative ossicular cadmium
      accumulation over a lifetime and possibly to cadmium-derived bone fragility in
      advanced age.

PMID- 11250051
TI  - The effect of polychlorinated biphenyls on the high affinity uptake of the
      neurotransmitters, dopamine, serotonin, glutamate and GABA, into rat brain
      synaptosomes.
AB  - Studies have shown that polychlorinated biphenyls (PCB) may affect cognitive
      functions both in human and also in experimental animals. We have investigated
      whether this effect could be caused by an inhibition of the uptake of selected
      neurotransmitters into rat brain synaptosomes. Ortho-chlorinated biphenyls were
      found to inhibit transmitter transport into synaptosomes from rat brain. In
      contrast, several nonortho-chlorinated biphenyls did not inhibit uptake. The
      uptake of dopamine, glutamate, GABA and serotonin was inhibited by the PCB
      mixtures, Aroclor 1242 and 1254. Under identical condition, the uptake of
      dopamine was inhibited more efficient than that of glutamate. The inhibition of
      neurotransmitter uptake was found to be dependent on the chlorination patterns of
      the PCB congeners, (i) ortho-chlorinated PCBs with four to five chlorine
      substituents (with the exception of 2,2',6,6'-TeCB) were the most effective
      inhibitors; (ii) hexa- or heptachlorinated PCBs were poor inhibitors or partial
      inhibitors (e.g. 2,2',4,4',5,5'-HCB) of glutamate and GABA uptake. Kinetic
      studies indicated that Aroclor 1242 inhibited dopamine uptake mainly
      competitively. The uptake of glutamate and GABA was inhibited in either a mixed
      competitive or in a non-competitive way, respectively. The neurotoxic
      consequences of the effect of different PCBs on neurotransmitter uptake on the
      uptake into synaptosomes are discussed.

PMID- 11250052
TI  - Nickel, cobalt and chromium-induced cytotoxicity and intracellular accumulation
      in human hacat keratinocytes.
AB  - Nickel, cobalt and chromium can induce allergic contact dermatitis (ACD) and may
      provoke irritant reactions in the skin. This study aimed at investigating
      cytotoxicity and cell viability along with intracellular metal accumulation in
      HaCaT human keratinocytes exposed to soluble forms of nickel, cobalt or chromium.
      The EC50 (24 h) values as detected by MTT test were 30 microM for sodium chromate
      (Na2CrO4), 475 microM for cobalt chloride (CoCl2) and 600 microM for nickel
      chloride (NiCl2). Chromium chloride (CrCl3) was not toxic up to 1 mM. No clear
      effects were observed after 4 h, but 24-h treatments with 1 mM CoCl2 or 10 microM
      Na2CrO(4) were found to almost completely abolish the ability of the cells to
      form colonies, whilst 1 mM NiCl2 reduced cellular survival to only 70% of control
      cultures. Intracellular accumulation of metals was evaluated by the use of
      radioisotopes at the EC50 value and at 1/10-1/5 of this concentration.
      Accumulation of Na2(51)CrO4 was linear with increasing dose. This was not the
      case for 63NiCl2 and 58CoCl2. All the metals were accumulated preferentially in
      the cytosols; 96% or more for 63NiCl2, approximately 90% for 58CoCl2 and 60-70%
      for Na2(51)CrO4. Finally, it was observed that HaCaT human keratinocytes can
      concentrate the metals present in the media up to 3.9 and 12.5 times for NiCl2
      and CoCl2, respectively, and up to 167 for Na2CrO4. These striking metal
      intracellular accumulation patterns, which have not been earlier described in
      keratinocytes, highlight the relevance of searching for specific biomarkers of
      early cellular toxic effects, such as cytosolic proteins that bind the metals.

PMID- 11250053
TI  - Nickel-induced proteins in human HaCaT keratinocytes: annexin II and
      phosphoglycerate kinase.
AB  - It has been established in previous in vitro experiments with human HaCaT
      keratinocytes that nickel becomes cytotoxic at concentrations higher than 100
      microM and that it is accumulated mainly in the cytosolic fraction (Ermolli et
      al., 2000). The aim of this work was to search possible biomarkers of metal
      insult, i.e. nickel-binding proteins or proteins differentially expressed in the
      cytosolic fraction of nickel-exposed cells (up to 1 mM nickel) as compared to
      controls. Cytosolic proteins were studied by isoelectric focusing (IEF) and two
      dimensional gel electrophoresis (2-DE). Separation by IEF revealed nickel-induced
      changes in the abundance of cytosolic proteins as visualised with nickel-nitrilo
      triacetic-alkaline phosphatase (Ni-NTA-AP) in blots. The cytosolic fraction of
      cells incubated with nickel, at concentrations over 100 microM, showed nickel
      binding components which were absent or present in significantly lower amounts in
      control cells. These proteins had isoelectric points (pIs) 6.9, 7.7 and 8.5.
      After 2-DE silver- and protein staining significantly increased abundance of four
      proteins was observed. Their pI values corresponded to those of the nickel
      binding ones seen after IEF. A protein with pI 6.9 had a molecular weight
      estimated to 38 kDa, two proteins with pI around 7.7 showed molecular weights of
      57 and 22 kDa, respectively and another protein with pI of 8.5 had a molecular
      weight of 33 kDa. The increased abundance of these components, both in IEF
      experiments and in 2-DE, correlated with the nickel concentration in the culture
      media. N-terminal amino acid sequencing and database search allowed
      identification of one a protein as phosphoglycerate kinase and another one as
      annexin II. The involvement of these proteins in cellular functions and their
      possible implications in the mechanism of nickel toxicity in keratinocytes are
      discussed. Some of these proteins may be biomarker candidates for effects of
      nickel exposure in human keratinocytes.

PMID- 11250054
TI  - Correlation of a specific mitochondrial phospholipid-phosgene adduct with
      chloroform acute toxicity.
AB  - The dose and time dependence of formation of a specific adduct between
      mitochondrial phospholipid and phosgene have been determined in the liver of
      Sprague-Dawley (SD) rats as well as in the liver and kidney of B6C3F1 mice after
      dosing with chloroform. Rats were induced with phenobarbital or non-induced.
      Determination of tissue glutathione (GSH) and of serum markers of hepatotoxicity
      and nephrotoxicity was also carried out. With dose-dependence experiments, a
      strong correlation between the formation of the specific phospholipid adduct, GSH
      depletion and organ toxicity could be evidenced in all the organs studied. With
      non-induced SD rats, no such effects could be induced up to a dose of 740 mg/kg.
      Time-course studies with B6C3F1 mice indicated that the specific adduct formation
      took place at very early times after chloroform dosing and was concurrent with
      GSH depletion. The adduct formed during even transient GSH depletion (residual
      level: 30% of control) and persisted after restoration of GSH levels. Following a
      chloroform dose at the hepatotoxicity threshold (150 mg/kg), the elimination of
      the adduct in the liver occurred within 24 h and correlated with the recovery of
      ALT, which was slightly increased (12 times) after treatment. Following a
      moderately nephrotoxic dose (60 mg/kg), the renal adduct persisted longer than 48
      h, when a 100% increase in blood urea nitrogen and a 40% increase in serum
      creatinine indicated the onset of organ damage. The formation of the adduct in
      the liver mitochondria of B6C3F1 mice was associated with the decrease of
      phosphatidyl-ethanolamine (PE), in line with previous results in rat liver
      indicating that the adduct results from the reaction of phosgene with PE. The
      adduct levels implicated the reaction of phosgene with about 50% PE molecules in
      the liver mitochondrial membrane of phenobarbital-induced SD rats and of about
      10% PE molecules of the inner mitochondrial membrane of the liver of B6C3F1 mice.
      The association of this adduct with the toxic effects of chloroform makes it a
      very good candidate as the primary critical alteration in the sequence of events
      leading to cell death caused by chloroform.

PMID- 11250055
TI  - Effect of butyl benzyl phthalate on reproduction and zinc metabolism.
AB  - Butyl benzyl phthalate (BBP) has been shown to be teratogenic. One mechanism
      contributing to the teratogenicity of several developmental toxicants, is
      chemical-induced changes in maternal zinc (Zn) metabolism which result in an
      increased synthesis of maternal liver metallothionein (Mt), and a subsequent
      reduction in Zn delivery to the conceptus. We investigated the effects of
      maternal BBP exposure on maternal-fetal Zn metabolism in Wistar rats. In study I,
      dams were gavaged with BBP (0,250,1000,1500 or 2000 mg/kg) on gestation days (GD)
      11 through 13, and killed on GD 20. Maternal toxicity was evident in the three
      highest dose groups. Embryo/fetal death and small pup weights and lengths were
      noted in the 2000 mg BBP/kg group. Fetuses in the 1500 and 2000 mg/kg groups were
      characterized by poor skeletal ossification, and a high frequency of cleft
      palate. Rib anomalies were observed in the three highest dose groups. Maternal
      liver Mt concentrations were only slightly elevated in the 1500 and 2000 mg/kg
      groups. In study II, dams treated as above, were gavaged with 65Zn and killed 18
      h later. While the 2000 mg/kg group had high percentages of 65Zn in some maternal
      tissues, sequestration of 65Zn in maternal liver was not evident. Thus, BBP is
      not a strong inducer of Mt, and the teratogenicity of BBP does not appear to be
      due to alterations in maternal and/or embryonic Zn metabolism.

PMID- 11250056
TI  - Decreased fumonisin hepatotoxicity in mice with a targeted deletion of tumor
      necrosis factor receptor 1.
AB  - Fumonisin B1 (FB1), a mycotoxin produced by Fusarium verticillioides and related
      fungi infests corn and other cereals, and causes a variety of toxic effects in
      different mammalian species. Hepatotoxicity is a common toxic response in most
      species. The cellular responses of FB1 involve inhibition of ceramide synthase
      leading to accumulation of free sphingoid bases and a corresponding induction of
      tumor necrosis factor alpha (TNFalpha). We recently reported that FB1
      hepatotoxicity was considerably reduced in a mouse strain lacking tumor necrosis
      factor receptor 2 (TNFR2 or TNFR1b). To further investigate the relative
      contribution of the two TNFalpha receptors (TNFR1 and TNFR2 or P55 and P75
      receptors) we evaluated the hepatotoxicity of FB1 in male C57BL/6J mice (WT) and
      a corresponding TNFR1 knockout (TNFRKO) strain, genetically modified by a
      targeted deletion of this receptor. The hepatotoxic effects of five daily
      injections of 2.25 mg/kg per day of FB1 were observed in WT but were reduced in
      TNFRKO, evidenced by the microscopic evaluation of the liver and increased
      concentrations of circulating alanine aminotransferase and aspartate
      aminotransferase. FB1 induced the expression of TNFalpha, and similar increases
      in free sphinganine and sphingosine in livers of both WT and TNFRKO mice. Results
      indicated that both P55 and P75 receptors are required for FB1-induced
      hepatotoxicity and TNFalpha plays an important role in such response in mouse
      liver.

PMID- 11250057
TI  - Effects of crocidolite asbestos on human bronchoepithelial-dependent fibroblast
      stimulation in coculture: the role of IL-6 and GM-CSF.
AB  - Cocultures of human pulmonary epithelial cells (BEAS-2B) and lung fibroblasts
      (WISTAR-38), representing two cell types of central regulatory potential in
      (chronic) lung disease, were used as an in vitro model to study the role of
      interleukin 6 (IL-6) and of granulocyte macrophage-colony stimulating factor (GM
      CSF) in early fibrogenesis. For this purpose, epithelial cells were pre-exposed
      to UICC crocidolite asbestos fibers or titanium dioxide (TiO2) particles for 96 h
      and subsequently cocultured with fibroblasts for additional 72 h. Gene expression
      of IL-6 or GM-CSF in both cell types as well as of alpha1 procollagens types I
      and III in fibroblasts was determined by RT-PCR. Synthesis of IL-6, GM-CSF or
      collagen I was quantified using IL-6 bioassay or ELISA tests, respectively. Both
      mediators were directly induced in bronchoepithelial cells by crocidolite but not
      by TiO2. Likewise, steady-state mRNA levels of procollagens as well as collagen
      synthesis were upregulated in cocultured fibroblasts. As a result of coculture,
      cytokine concentrations were synergistically enhanced and further increased by
      crocidolite in a dose-dependent manner. Suppression of cytokine induction by
      corresponding neutralizing antibodies consistently abrogated collagen
      enhancement. Direct stimulation of fibroblast monocultures with recombinant human
      IL-6 or GM-CSF significantly increased collagen synthesis and transcription in a
      dose-dependent manner. Thus, our results demonstrate that crocidolite selectively
      stimulated production of IL-6 and GM-CSF in bronchoepithelial cells. In
      epithelial-fibroblast interactions, these mediators appear to play a key role in
      regulating fibroblast activity, indicating a close correlation between these
      cytokines and the fibrogenic potential of particulates.

PMID- 11250058
TI  - The mechanism for lindane-induced inhibition of steroidogenesis in cultured rat
      Leydig cells.
AB  - The in vitro effect of the gamma-isomer of hexachlorocyclohexane, lindane, on rat
      Leydig cell steroidogenesis was studied. Leydig cells from mature male rats were
      incubated with human chorionic gonadotropin (hCG, 1 IU) for 3 h at 34 degrees C
      in the presence of different doses of lindane (2-200 microg/ml; 2-200 ppm).
      Results demonstrate that lindane produces a dose-dependent inhibition of
      testosterone production in hCG-stimulated Leydig cells. The decreased
      testosterone synthesis was accompanied with a half-reduced LH/hCG receptor number
      without any modification in the K(d) value. In addition, lindane also decreased
      cAMP production. These effects were not due to a detrimental action of lindane on
      cell viability. Results of this study demonstrate a direct inhibitory action of
      lindane on testicular steroidogenesis, at least in part, through a reduction in
      the classical second messenger production involved in this pathway.

PMID- 11250059
TI  - 2,3,7,8-tetrachlorodibenzo-p-dioxin and natural immunity: lack of an effect on
      the complement system in a guinea pig model.
AB  - We examined the complement system as a potential target for toxicity of 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) in normal Hartley guinea pigs. Guinea pigs
      were injected intravenously with 0.5 microg/kg TCDD and bled at weekly intervals
      up to 1 month following injection. Serum samples were collected at each time
      point and assayed for total hemolytic complement activity (CH50), alternative
      pathway complement activity (AH50) and complement component C4 functional
      activity. Injection of TCDD led to a wasting syndrome, as observed by a lower
      body weight gain in TCDD-treated animals when compared to control animals.
      However, at this dose, TCDD failed to induce any significant change in complement
      activity as determined by all three methods used in this study. The results
      indicate that, at 0.5 microg/kg body weight, a dose slightly lower than the LD50
      value in guinea pigs, TCDD fails to affect the complement system.

PMID- 11250060
TI  - Cooperation of the basal ganglia, cerebellum, sensory cerebrum and hippocampus:
      possible implications for cognition, consciousness, intelligence and creativity.
AB  - It is suggested that the anatomical structures which mediate consciousness
      evolved as decisive embellishments to a (non-conscious) design strategy present
      even in the simplest unicellular organisms. Consciousness is thus not the
      pinnacle of a hierarchy whose base is the primitive reflex, because reflexes
      require a nervous system, which the single-celled creature does not possess. By
      postulating that consciousness is intimately connected to self-paced probing of
      the environment, also prominent in prokaryotic behavior, one can make mammalian
      neuroanatomy amenable to dramatically straightforward rationalization. Muscular
      contraction is the nervous system's only externally directed product, and the
      signaling routes which pass through the various brain components must ultimately
      converge on the motor areas. The function of several components is still
      debatable, so it might seem premature to analyze the global operation of the
      circuit these routes constitute. But such analysis produces a remarkably simple
      picture, and it sheds new light on the roles of the individual components. The
      underlying principle is conditionally permitted movement, some components being
      able to veto muscular contraction by denying the motor areas sufficient
      activation. This is true of the basal ganglia (BG) and the cerebellum (Cb), which
      act in tandem with the sensory cerebrum, and which can prevent the latter's
      signals to the motor areas from exceeding the threshold for overt movement. It is
      also true of the anterior cingulate, which appears to play a major role in
      directing attention. In mammals, the result can be mere thought, provided that a
      second lower threshold is exceeded. The veto functions of the BG and the Cb stem
      from inhibition, but the countermanding disinhibition develops at markedly
      different rates in those two key components. It develops rapidly in the BG,
      control being exercised by the amygdala, which itself is governed by various
      other brain regions. It develops over time in the Cb, thereby permitting
      previously executed movements that have proved advantageous. If cognition is
      linked to overt or covert movement, intelligence becomes the ability to
      consolidate individual motor elements into more complex patterns, and creativity
      is the outcome of a race-to-threshold process which centers on the motor areas.
      Amongst the ramifications of these ideas are aspects of cortical oscillations,
      phantom limb sensations, amyotrophic lateral sclerosis (ALS) the difficulty of
      self-tickling and mirror neurons.

PMID- 11250061
TI  - Role of integrins in the peripheral nervous system.
AB  - Integrins, a subgroup of adhesion receptors, are transmembrane glycoproteins that
      mediate interactions between cytoplasm and the extracellular environment. These
      interactions influence, among others, events such as cell migration,
      proliferation, and differentiation. Differential expression of integrins is
      developmentally regulated in the peripheral nervous system (PNS) and is
      associated with crucial events in both physiological and pathological processes.
      Preliminary studies suggest that integrin expression influences neural crest cell
      migration, axonal outgrowth, and Schwann cell differentiation. Similarly, the
      abnormal expression of integrins or their ligands, is associated with
      degenerative, inflammatory, and malignant disorders of the PNS. Finally,
      integrins participate in the complex interactions that promote repair of the PNS.
      A better comprehension of the role of integrins in the PNS, their protein
      interactions and transducing signals is being achieved by selected biochemical
      and genetic experiments. Here we review a large bias of evidence suggesting the
      key functions for integrins in the PNS.

PMID- 11250062
TI  - Nitric oxide as modulator of neuronal function.
AB  - The gas NO is a messenger that modulates neuronal function. The use of NO donors
      and NO synthase inhibitors as pharmacological tools revealed that this free
      radical is probably implicated in the regulation of excitability and firing, in
      long-term potentiation and long-term depression, as well as in memory processes.
      Moreover, NO modulates neurotransmitter release. In vivo and in vitro studies
      have shown that, in all brain structures investigated, endogenous NO modulates
      the release of several neurotransmitters, such as acetylcholine, catecholamines,
      excitatory and inhibitory amino acids, serotonin, histamine, and adenosine. In
      most cases, enhanced NO level in the tissue increases the release of
      neurotransmitters, although decreasing effects have also been observed. Cyclic 3'
      5' guanosine monophosphate and glutamate mediate the modulation of transmitter
      release by NO. Recent observations suggest that the release of some transmitters
      is dually influenced by NO. Thus, besides modulation by presynaptically located
      auto- and heteroreceptors, NO released from nitrergic neurons seems to play a
      universal role in modulating the release of transmitters in the brain.

PMID- 11250063
TI  - Otx genes in brain morphogenesis.
AB  - Most of the gene candidates for the control of developmental programmes that
      underlie brain morphogenesis in vertebrates are the homologues of Drosophila
      genes coding for signalling molecules or transcription factors. Among these, the
      orthodenticle group includes the Drosophila orthodenticle (otd) and the
      vertebrate Otx1 and Otx2 genes, which are mostly involved in fundamental
      processes of anterior neural patterning. These genes encode transcription factors
      that recognise specific target sequences through the DNA binding properties of
      the homeodomain. In Drosophila, mutations of otd cause the loss of the
      anteriormost head neuromere where the gene is transcribed, suggesting that it may
      act as a segmentation "gap" gene. In mouse embryos, the expression patterns of
      Otx1 and Otx2 have shown a remarkable similarity with the Drosophila counterpart.
      This suggested that they could be part of a conserved control system operating in
      the brain and different from that coded by the HOX complexes controlling the
      hindbrain and spinal cord. To verify this hypothesis a series of mouse models
      have been generated in which the functions of the murine genes were: (i) fully
      inactivated, (ii) replaced with each others, (iii) replaced with the Drosophila
      otd gene. Otx1-/- mutants suffer from epilepsy and are affected by neurological,
      hormonal, and sense organ defects. Otx2-/- mice are embryonically lethal, they
      show gastrulation impairments and fail in specifying anterior neural plate.
      Analysis of the Otx1-/-; Otx2+/- double mutants has shown that a minimal
      threshold level of the proteins they encode is required for the correct
      positioning of the midbrain-hindbrain boundary (MHB). In vivo otd/Otx reciprocal
      gene replacement experiments have provided evidence of a general functional
      equivalence among otd, Otx1 and Otx2 in fly and mouse. Altogether these data
      highlight a crucial role for the Otx genes in specification, regionalization and
      terminal differentiation of rostral central nervous system (CNS) and lead to
      hypothesize that modification of their regulatory control may have influenced
      morphogenesis and evolution of the brain.

PMID- 11250064
TI  - Nitric oxide and peroxynitrite as factors to stimulate neurotransmitter release
      in the CNS.
AB  - This review summarizes the stimulatory potentials of NO and peroxynitrite (OONO-)
      on neurotransmitter release in the central nervous system. Exogenous and
      endogenous NO stimulates to release neurotransmitter. NO synthesized
      intracellularly diffuses out through neuronal membrane and acts on the outer side
      of membrane to depolarize neuronal membrane, which triggers neurotransmitter
      release. NO-induced release of neurotransmitters is mediated by Ca2+-dependent
      and -independent processes. The latter process is operated by reverse process of
      the Na+-dependent carrier-mediated neurotransmitter uptake system or by unknown
      mechanisms. Ca2+-dependent release of neurotransmitter occurs in part subsequent
      to increase in Ca2+ influx via VDCCs, although N-type VDCCs may not involve in
      this action of NO because of suppression of Ca2+ influx through N-type VDCCs by
      NO. Participation of cGMP formation by NO on neurotransmitter release is
      controversial. A superoxide scavenger, Ca2+, Zn(2+)-superoxide dismutase,
      abolishes NO-induced neurotransmitter release and synthesized OONO- induces
      neurotransmitter release, indicating that OONO- participates in NO-evoked
      neurotransmitter release.

PMID- 11250066
TI  - Heparanase: a key enzyme involved in cell invasion.

PMID- 11250065
TI  - Randomized trials of high dose chemotherapy for breast cancer.
AB  - 'Now is not the end. It is not even the beginning of the end. But it is, perhaps,
      the end of the beginning'Winston Churchill in a speech to the Canadian Senate and
      House of Commons, December 30, 1941. In laboratory models of cancer, dose of
      cytotoxic chemotherapy correlates with curative therapy, while cumulative dose is
      associated with longer survival for those who are not cured. These observations
      suggests a strategy of using high doses when cure is the objective but smaller
      doses over a prolonged period when palliation and survival are the goal. A
      strategy combining repetitive cycles of higher doses of cytotoxic therapy,
      followed by the optimal combination of hormonal and biological agents based on
      the tumor's receptors might contribute to both the highest possible cure rate and
      the longest survival. The development of bone marrow transplant (BMT) for
      leukemias, and its subsequent modification for support after high dose therapy
      for other malignancies, has a long, complex and emotional history in medicine. At
      least partly because of firmly held opinions and the way large randomized trials
      are funded in the United States, few American randomized trials of BMT or high
      dose therapy strategies have been completed. The vast majority of published
      randomized BMT and high dose studies are European. Interestingly, in contrast,
      two large American randomized trials of high dose chemotherapy for breast cancer
      had actually completed accrual. Accrual on a third was on target until the
      presentation of five very small or very early randomized trials at the American
      Society of Clinical Oncology meeting in May of 1999. Results from some of these
      trials, which were analyzed after a relatively brief follow-up, are too premature
      to allow definitive conclusions. Nevertheless, these data have been over and
      misinterpreted within the scientific and lay communities. The remaining studies
      included a limited number of patients, thus restricting the statistical power of
      the observations. The desire for quick answers impeded dispassionate analysis of
      the available data. The opportunity for collegial review of the data further
      deteriorated with another round of press coverage when the data from the South
      African adjuvant study were found to be unreliable. Rather than increasing
      commitment to accrual on randomized and appropriate pilot trials, accrual to the
      only large American study in existence at that time trickled to a halt. In
      response to press coverage, Susan Edmonds from the Fred Hutchinson Cancer
      Research Center observed that 'the NYT article tends to cast shadows generally on
      the therapy and those providing the therapy rather than pointing out early in the
      article (where the public will readily see it) that there are a number of very
      credible research institutions conducting research directed at breast cancer,
      some looking at high dose chemotherapy and stem cell transplantation.' Dr.
      Rodenhuis, presenting the large positive Dutch Randomized study (funded by the
      Dutch insurance industry) at ASCO in 2000, commented on the 'unreasonably high
      expectations until 1999' and 'unreasonably negative [opinion-ed] since 1999' for
      high dose adjuvant chemotherapy for breast cancer.

PMID- 11250067
TI  - Homologous recombination as a mechanism of carcinogenesis.
AB  - Cancer develops when cells no longer follow their normal pattern of controlled
      growth. In the absence or disregard of such regulation, resulting from changes in
      their genetic makeup, these errant cells acquire a growth advantage, expanding
      into pre-cancerous clones. Over the last decade many studies have revealed the
      relevance of genomic mutation in this process, be it by misreplication,
      environmental damage or a deficiency in repairing endogenous and exogenous
      damage. Here we discuss homologous recombination as another mechanism that can
      result in loss of heterozygosity or genetic rearrangements. Some of these genetic
      alterations may play a primary role in carcinogenesis, but they are more likely
      to be involved in secondary and subsequent steps of carcinogenesis by which
      recessive oncogenic mutations are revealed. Patients whose cells display an
      increased frequency of recombination also have an elevated frequency of cancer,
      further supporting the link between recombination and carcinogenesis. In
      addition, homologous recombination is induced by a wide variety of carcinogens,
      many of which are classically considered to be efficiently repaired by other
      repair pathways. Overall, homologous recombination is a process that has been
      widely overlooked but may be more central to the process of carcinogenesis than
      previously described.

PMID- 11250069
TI  - Function of the c-Myc oncoprotein in chromatin remodeling and transcription.
AB  - Deregulated expression of the c-myc proto-oncogene contributes to malignant
      progression of a variety of tumors. The c-Myc protein (or Myc) is a transcription
      factor that positively or negatively regulates expression of distinct sets of
      target genes. Transcriptional activation by Myc is mediated through dimerization
      with Max and binding to the DNA consensus sequence CA(C/T)GTG (the E-box).
      Transcriptional inhibition is mediated through distinct DNA elements, and may be
      due to functional interference with factors that transactivate via these
      sequences. We review here our current knowledge on these transcriptional
      activities of Myc and their relationship to its biological function. The findings
      that Myc interacts with subunits of histone acetyl-transferase (HAT) complexes
      and of the ATP-dependent chromatin remodeling complex, SWI/SNF, suggest that
      localized changes in chromatin structure may mediate Myc function. We present a
      working hypothesis for the concerted action of HAT and SWI/SNF complexes in Myc
      activated transcription and argue that this model should prompt re-thinking of
      the experimental strategies and criteria used to identify Myc target genes.

PMID- 11250068
TI  - Regulation of the retinoblastoma tumor suppressor protein by cyclin/cdks.
AB  - The retinoblastoma tumor suppressor protein (pRB) is a paradigm for understanding
      cell cycle- and proliferation-dependent transcription and how deregulation of
      this process contributes to the neoplastic process in humans. The ability of pRB
      to regulate transcription, and consequently cell proliferation and
      differentiation, is regulated by the activity of cyclin/cdks. In general,
      phosphorylation of pRB by cyclin/cdks inactivates pRB-mediated transcriptional
      inhibition and growth suppression. However, it is apparent that pRB is a multi
      functional protein that can inhibit transcription through various mechanisms.
      This review focuses on recent data to suggest that different pRB functions are
      progressively and cooperatively inactivated by multiple cyclin/cdk complexes
      during G1- and S-phase. The implications of such a model for pRB-mediated tumor
      suppression are discussed.

PMID- 11250070
TI  - Expression of telomerase reverse transcriptase and telomere elongation during
      sexual maturation in Paramecium caudatum.
AB  - Paramecium caudatum has a sexually immature period that lasts for about 60
      fissions. To examine the possibility that telomere length is one of the
      determining factors of the duration of immaturity, we cloned the telomerase
      reverse transcriptase (TERT) gene from P. caudatum, and analyzed its expression
      levels at mRNA, telomerase activity, and telomere length during the course of
      clonal division. Paramecium TERT (Pc_TERT) cDNA encodes a basic protein of 107
      kDa that harbors conserved RT motifs, T motif, CP motif, and N motif. Pc_TERT
      mRNA is expressed at very low levels only detectable by RT-PCR, but
      constitutively, during immature and mature periods, exhibiting abundant
      telomerase activity. No clear phase shift in Pc_TERT expression, telomerase
      activity, or telomere length was observed at the point of maturation in P.
      caudatum. Instead, the telomere elongates successively as cells divide in P.
      caudatum, although a close species, P. tetraurelia, was reported to keep the
      length constant. We discuss possible mechanisms for the expression of sexual
      activity associated with telomere length in P. caudatum.

PMID- 11250071
TI  - Genomic organization and transcriptional analysis of STDEFICIENS in Solanum
      tuberosum L.
AB  - The genomic organization of STDEFICIENS (STDEF), the potato orthologous gene to
      DEFICIENS (DEF) from Antirrhinum majus and APETALA3 (AP3) from Arabidopsis
      thaliana, has been investigated. Southern-blot analysis on genomic DNA from
      dihaploid potato lines, using 5'-gene specific probes, revealed polymorphisms
      that were consistent with the existence in potato of at least two copies of STDEF
      per haploid genome. This was confirmed by the detection of at least six different
      STDEF transcripts in the common tetraploid potato S. tuberosum. Genes for two of
      the STDEF loci, here designated as STDEF-1 and STDEF-2, have been identified as
      corresponding to the previously described pD13 and pD12 genomic clones,
      respectively (Garcia-Maroto et al., 1993). In addition we have characterised the
      transcriptional STDEF unit. The main transcription start has been identified
      around 90 nt upstream of the putative initiation ATG codon, at a CAAATC motif,
      conserved in AP3. An additional transcription initiation site was detected by 5'
      RACE analysis about 300 nt upstream of the main start, which has been confirmed
      by reverse transcriptase - polymerase chain reaction (RT-PCR) amplification from
      the longer transcripts. A comparison of the promoter regions for pD12, pD13 and
      AP3 indicates a similar overall structure, but reveals the existence of a great
      divergence between pD12 and pD13 in a promoter region that should contain
      important cis-regulatory elements. This raises the possibility of a differential
      regulation for the two STDEF genes.

PMID- 11250072
TI  - Regulation of the CCAAT-Binding NF-Y subunits in Arabidopsis thaliana.
AB  - NF-Y is a CCAAT-specific binding factor composed of three distinct subunits. In
      vertebrates and fungi all three subunits are encoded by evolutionary conserved
      single copy genes. In this report we have cloned twenty-three NF-Y genes in A.
      thaliana, assessed their mRNA expression levels in a large number of tissues and
      confirmed that indeed multiple CCAAT-binding activities are present. Alignments
      of the genes coding for the three NF-Y subunits yield a considerable amount of
      information concerning the divergence/conservation of protein subdomains and of
      single residues within the conserved parts. Careful evaluation of mRNA expression
      levels by sensitive RT-PCR assays provide evidence that all three subunits have
      members that are ubiquitous and others that are tissue-specific and induced only
      after the switch to reproductive growth phase, in flowers and siliques.

PMID- 11250073
TI  - Genomic sequence and expression analyses of human chromatin assembly factor 1
      p150 gene.
AB  - Chromatin assembly factor-1 (CAF-1) plays essential roles in eukaryotic chromatin
      assembly during DNA replication (Smith and Stillman, 1989. Cell 58, 15-25),
      (Krude, 1999. Eur. J. Biochem. 263, 1-5). Its p150 subunit, involved in
      interaction with histone H3 and H4, is critical to the CAF-1 nucleosome assembly
      activity. In this study, we sequenced a 96-kb genomic DNA region that includes a
      42.8-kb CAF-1 p150 subunit gene (CHAF1A), and a 41.1-kb EEN gene. A scripted
      bioinformatics analysis pipeline (research agent) has been set up to annotate the
      BAC sequence with a set of integrated algorithms. The CAF-1 p150 subunit gene
      contains 15 exons and 14 introns. The promoter region is characterized by
      deletional analyses, revealing a potential repressor. Tissue-correlated
      alternative splicing forms of the transcript was initially identified by EST
      clustering analysis, then confirmed by RT-PCR which resulted more splicing forms
      than computational prediction.

PMID- 11250074
TI  - Lack of ultraviolet-light inducibility of the medakafish (Oryzias latipes) tumor
      suppressor gene p53.
AB  - P53 is by far the most frequently altered gene in mammalian tumors. However, so
      far not a single p53 lesion has been reported in malignancies of cancer model
      systems in lower vertebrates. For analyzing the function of p53 in lower
      vertebrates, the gene was cloned from the medakafish (Oryzias latipes). Despite
      some differences in the genomic organization, the fish p53 amino acid sequence is
      highly conserved. Contrary to higher vertebrates, the level of p53 mRNA in medaka
      embryos gradually increases during embryogenesis. High expression of the p53 mRNA
      was detected in melanoma cells compared to undetectable expression of the gene in
      embryonic stem cells and fibroblasts. No effect of ultraviolet (UV) irradiation
      on the expression of p53 in cell cultures as well as in medaka fry was observed,
      indicating a possible difference in the function of p53 in lower vertebrates.

PMID- 11250075
TI  - Characterization of the X-linked murine centrin Cetn2 gene.
AB  - A multi-gene family (Cetn1, Cetn2, and Cetn3) encodes the calcium-binding
      protein, centrin, in the mouse. This work characterizes the Cetn2 gene.
      Structurally, Cetn2 consists of five exons and four introns, and contains a
      classical TATA-less promoter. Cetn2 has two alternate transcription start sites,
      and a single length 3' untranslated region. Fluorescence in situ hybridization
      demonstrates that Cetn2 is an X-linked gene whose alleles replicate
      asynchronously during S-phase. Cetn2 encodes a 172 amino acid protein, with a
      predicted molecular mass of 19,795 Da (pI=4.71), that contains all of the
      defining characteristics of centrin. Northern blot analysis indicates that Cetn2
      is ubiquitously expressed in the tissues of adult mice. RT-PCR shows that Cetn2
      and Cetn3, but not Cetn1, are expressed in NIH 3T3 cells. Immunofluorescence
      microscopy demonstrates that mouse centrin 2 protein localizes to the region
      immediately surrounding the centrioles in the centrosome of NIH 3T3 cells.

PMID- 11250076
TI  - Characterization of the mouse liver fructose-1,6-bisphosphatase gene.
AB  - A cDNA encoding fructose-1,6-bisphosphatase (FBPase) was isolated from mouse
      liver RNA. The cDNA encodes a polypeptide of 338 amino acids (36.9 kDa). The
      liver and muscle FBPase isoenzymes of the mouse show positional identities of 69%
      at the cDNA level and 72% at the protein primary structure level. Starting from
      genomic YAC libraries and based upon the cDNA sequence all functional parts of
      the mouse liver FBPase gene (including exon-intron boundaries) were PCR-amplified
      and sequenced. The 5'-flanking regions of the liver and muscle FBPase genes were
      compared and showed no sequence similarity. Both genes are co-localized at
      chromosome 13B3-C1. The transcriptional start site was assigned to a guanine 118
      bases before the start codon in the liver FBPase gene. An analysis of the steady
      state mRNA levels of liver and muscle FBPase in various mouse tissues was
      performed by Northern blotting and RT/PCR.

PMID- 11250077
TI  - Monitoring promoter activity and protein localization in Mycobacterium spp. using
      green fluorescent protein.
AB  - Two green fluorescent protein (Gfp) fusion vectors were constructed for use in
      Mycobacterium spp. The first plasmid facilitates quantification of mycobacterial
      promoter activity. The second vector permits construction of translational
      fusions of mycobacterial proteins to Gfp in order to study subcellular
      localization including protein secretion. Using this translational fusion
      construct, we verify that a Gfp fusion to the putative secreted M. tuberculosis
      protein ChoD is translocated to the extracellular milieu when cloned and
      expressed in Mycobacterium smegmatis.

PMID- 11250078
TI  - Characterization and expression of the genes for cytochrome c oxidase subunit VIb
      (COX6b) from rice and Arabidopsis thaliana.
AB  - Many of the subunits of cytochrome c oxidase (COX) in the mitochondria of higher
      plants are encoded by nuclear genes. These genes are less characterized compared
      to mitochondrial-encoded genes. We previously isolated a cDNA encoding COX6b
      (designated OsCOX6b1 in this study) from the rice nuclear genome and analyzed its
      expression. The deduced protein had an extended N-terminus compared with human
      and yeast COX6b proteins. In this study, we identified another COX6b gene
      (OsCOX6b2) in rice and revealed that it was actually expressed. The deduced
      protein of this gene did not have an extended N-terminus and had about the same
      size as the human and yeast proteins. Genomic Southern hybridization analysis
      revealed that there was at least one OsCOX6b-homologus sequences in the rice
      genome other than OsCOX6b1 and OsCOX6b2. Furthermore, we identified three COX6b
      genes in a dicotyledonous plant, Arabidopsis thaliana. One of these genes
      (AtCOX6b1) was relatively long, with a length similar to that of OsCOX6b1, and
      the other two (AtCOX6b2 and AtCOX6b3) were shorter, with lengths similar to the
      length of OsCOX6b2. Genomic Southern hybridization analysis indicated there were
      no additional COX6b genes in the Arabidopsis genome. The coding regions of
      OsCOX6b1 and AtCOX6b1 were separated by four introns and those of OsCOX6b2,
      AtCOX6b2 and AtCOX6b3 were separated by three introns. A Northern hybridization
      analysis showed that OsCOX6b1, AtCOX6b1 and AtCOX6b3 were expressed in all organs
      examined, although with some differences in the amount of expression among the
      organs. OsCOX6b2 and AtCOX6b2 were strongly expressed in roots but most of the
      transcripts of AtCOX6b2 were degraded. The evolution of COX6b genes from rice and
      Arabidopsis is discussed.

PMID- 11250079
TI  - Molecular cloning and characterization of human VPS18, VPS 11, VPS16, and VPS33.
AB  - In multicellular organisms, the delivery of proteins to lysosomes is essential.
      Many of the genes necessary for this process have first been identified by their
      requirement for vacuolar delivery in yeast. A subset of these genes, the four
      class C vps genes, is necessary for the delivery of endocytic and biosynthetic
      cargo in yeast, and also in Drosophila. Here, we describe the sequence and
      expression pattern of four human homologs of these genes. This initial molecular
      description of these four genes is an important step towards their evaluation as
      candidate genes that may be involved in the pathogenesis of Hermansky-Pudlak
      syndrome-related diseases.

PMID- 11250080
TI  - Cloning and characterization of Chinese hamster homologue of yeast DBF4 (ChDBF4).
AB  - The Dbf4 protein is the regulatory subunit of Cdc7 serine/threonine kinase, which
      is essential for entry into S phase. We report here the cloning and initial
      characterization of the Chinese hamster homologue of yeast DBF4. The deduced
      ChDbf4 protein contains 676 amino acids with a predicted molecular mass of 75.8
      kDa, and shares extensive identity overall with those of human (68%) and mouse
      (73%). The ChDBF4 mRNA level was barely detectable in the cells arrested in the
      quiescent stage (G(0)) by isoleucine starvation. When cells in G(0) were released
      into the cell cycle, the ChDBF4 mRNA level did not significantly change until the
      cells reached the G(1)/S boundary, when the level rapidly increased and reached
      approximately 70% of the maximum level that was observed in mid to late S phase.
      Interestingly, gamma-irradiation rapidly and transiently downregulated the level
      of ChDBF4 mRNA in asynchronous cell populations. Since Dbf4-Cdc7 kinase is
      involved in the regulation of replication initiation, which can be transiently
      downregulated by irradiation (Larner et al., 1994. Mol. Cell. Biol. 14, 1901, our
      data raise the possibility that the downregulation of DBF4 (and, thus, the Cdc7
      kinase activity) by irradiation may play a role in the cell-cycle checkpoint that
      functions at the G(1)/S transition and in S phase (Lee et al., 1997. Proc. Natl.
      Acad. Sci. USA 94, 526).

PMID- 11250081
TI  - Physical and genetic characterization of the genome of Magnetospirillum
      magnetotacticum, strain MS-1.
AB  - Pulsed-field gel analysis of Magnetospirillum magnetotacticum, strain MS-1,
      indicates that the genome is a single, circular structure of about 4.3 mb. A few
      genes, identified by sequence similarity, have been localized and arranged in a
      map with dnaA, indicating the presumed origin of replication. There are at least
      two rRNA operons. In addition, rRNA genes are found on a 40 kb, possibly
      extrachromosomal, structure. The genes thought to be involved in magnetite
      synthesis, bfr and magA, are located in the same 17% of the genome. A one base
      pair-overlap seen in the bfr genes of MS-1 is found also in the closely related
      magnetic strain AMB-1, but not in the non-magnetic relative A. itersonii.

PMID- 11250082
TI  - Evolutionary relationships of the glucokinase from the amitochondriate protist,
      Trichomonas vaginalis.
AB  - Two genes coding for Trichomonas vaginalis glucokinase were isolated and
      sequenced. The putative translation products have molecular masses of 41,584 and
      41,772 Da, corresponding to 375 and 377 amino acids, respectively. These values
      agree with data determined by sodium dodecylsulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) for the enzyme purified from the organism. The two
      sequences showed 78% amino acid identity. The sequences and their phylogenetic
      reconstruction show that they are members of a glucokinase/fructokinase protein
      family found in eubacteria and also in the eukaryote Giardia lamblia and are only
      distantly related to typical eukaryotic hexokinases. The results indicate that
      the evolutionary past of this enzyme, catalyzing the first step of glycolysis in
      T. vaginalis, is different from that of the enzyme performing this key role in
      almost all other eukaryotes.

PMID- 11250083
TI  - Mouse phosphoglycerate mutase M and B isozymes: cDNA cloning, enzyme activity
      assay and mapping.
AB  - Two mouse cDNAs encoding the non-muscle-specific or brain isoform (type B, Pgam1)
      and the muscle-specific isoform (type M, Pgam2) of phosphoglycerate mutase (PGAM)
      were isolated and characterized. Pgam1 contains a 765 bp open reading frame (ORF)
      coding for a 254-residue protein while Pgam2 contains a 762 bp ORF coding for a
      253-residue protein. The deduced proteins of mouse Pgam1 and Pgam2 are highly
      similar to those of human and rat (> or = 93% similarity). Northern blot analysis
      showed that the expression patterns of Pgam1 and Pgam2 were distinct. Pgam1 was
      expressed as a 2.1-kb transcript highly in brain and kidney and moderately in
      liver, thyroid, stomach and heart, whereas Pgam2 was expressed as a 1.0-kb
      transcript highly in muscle, testis and moderately in heart and lung, but was not
      detectable in the other six tissues examined. Transfecting the cDNA fragments
      containing the entire ORFs of these two cDNAs into COS7 cells for transient
      expression, respectively, the enzyme activities of mouse Pgam1 and Pgam2 were
      detected to be 2.2-2.5 times of those of COS7 cells and COS7 cells transfected
      with vector, proving the validity of mouse Pgam1 and Pgam2 cDNAs we report here.
      Pgam1 and Pgam2 were assigned to 116.16 cR from D19Mit52 and 29.57 cR from
      D11Mit129, respectively, by radiation hybrid method. The partial genomic sequence
      of Pgam2 was determined, which showed that mouse Pgam2 consisted at least three
      exons and two introns. In addition, a pseudogene of Pgam1, Pgam1-ps1, was
      identified from mouse genomic sequence.

PMID- 11250084
TI  - Identification of the cobalamin-dependent methionine synthase gene, metH, in
      Vibrio fischeri ATCC 7744 by sequencing using genomic DNA as a template.
AB  - To confirm the presence of cobalamin-dependent methionine synthase (CDMS) in
      luminous bacteria, which is a prerequisite for the substantiation of our
      proposals on the physiological function of the lux operon, we identified the CDMS
      gene (metH) in Vibrio fischeri ATCC 7744. Two partial metH sequences, one located
      near the 5'-terminus of the gene and the other near the 3'-terminus, were
      sequenced by a PCR based method. To design a new set of PCR primers located on
      the two flanking regions of the gene, the genomic DNA was sequenced by SUGDAT
      method (sequencing using genomic DNA as a template) upstream or downstream from
      the respective partial gene sequences. Subsequently a 4.2 kb DNA fragment
      containing the whole metH was amplified by PCR and sequenced. The number of amino
      acid residues comprising the protein (1226 amino acids) was comparable to those
      of known CDMSs. The deduced amino acid sequence showed 85, 74, 55, 31, 30, 52, or
      52% identity with that of Vibrio cholerae, Escherichia coli, Deinococcus
      radiodurans, Synechocystis PCC6803, Mycobacterium tuberculosis, Caenorhabditis
      elegans or Homo sapiens, respectively. All the predicted amino acid residues for
      the binding of cobalamin and S-adenosylmethionine were conserved. In the
      regulatory region of the V. fischeri metH, the binding site of the met repressor,
      MetJ, was present, although the site is atypically not present in E. coli metH or
      Salmonella typhimurium metH. It was shown that nucleotide sequences, even long
      ones, can be determined without a cloning step, if only parts of the DNA fragment
      to be sequenced are amplified by PCR.

PMID- 11250085
TI  - Improved plasmid vectors for the production of multiple fluorescent protein
      fusions in Bacillus subtilis.
AB  - The intrinsically fluorescent green fluorescent protein has been used in many
      laboratories as a cytological marker to monitor protein localisation in live
      cells. Multiple spectrally modified mutant versions and novel fluorescent
      proteins from other species have subsequently been reported and used for
      labelling cells with multiple fluorescent protein fusions. In this work we report
      the design and use of vectors containing some of these spectral variants of GFP
      for use in the Gram positive bacterium Bacillus subtilis. These vectors
      complement those previously described (Lewis and Marston, 1999. Gene 227, 101
      109) to provide a large suite of plasmid vectors for use in this and other
      related Gram positive organisms. Using these vectors we have been able to
      directly demonstrate the sequential assembly/disassembly of proteins involved in
      the generation of cellular asymmetry during development.

PMID- 11250087
TI  - Suppression of agglomeration in fluidized bed coating. IV. Effects of sodium
      citrate concentration on the suppression of particle agglomeration and the
      physical properties of HPMC film.
AB  - We previously reported that sodium citrate (Na citrate), which is a high order
      salt in the Hofmeister's series, greatly suppressed particle agglomeration in
      fluidized bed coating (Pharm. Res., 16 (1999), 1616-1620). In this paper, we
      studied the effects of Na citrate concentration on the particle agglomeration in
      fluidized bed coating and on the structure of coated film on the particles.
      Spherical granules made of crystalline cellulose (Celphere) containing phenacetin
      were coated in a fluidized bed with the aqueous coating solution of
      hydroxypropylmethyl cellulose (HPMC) containing Na citrate at various
      concentrations. The particle diameter and drug release profile of coated
      particles, and the physical properties, i.e. tensile strength, elongation
      percentage at break, porosity and pore size distribution, of the HPMC cast film
      were investigated. The particle agglomeration was suppressed with the increasing
      Na citrate concentration. It is considered that the increase in the suppression
      effect was caused by the salting-out effect of the increased Na citrate. In the
      HPMC cast film system, the tensile strength and elongation percentage decreased
      and the porosity and cumulative pore volume increased with an increase in Na
      citrate concentration. It is considered that the increase in the porosity by
      adding Na citrate resulted from a phase separation due to the salting-out during
      the film forming process. The drug release rate from coated particles also
      increased with the increasing Na citrate concentration. It can be concluded that
      the increase in the release rate was due to the increase in porosity of the HPMC
      coated film caused by the increased Na citrate concentration.

PMID- 11250088
TI  - Parenteral water/oil emulsions containing hydrophilic compounds with enhanced in
      vivo retention: formulation, rheological characterisation and study of in vivo
      fate using whole body gamma-scintigraphy.
AB  - The preparation and characterization of parenteral water-in-oil (w/o) emulsions
      with a potential for sustained release of hydrophilic drugs was described with
      emphasis on rheological behaviour and spreading phenomenon after intramuscular
      (i.m.) injection in rabbit thigh muscle. Both steady state and dynamic
      rheological parameters were investigated showing Newtonian behaviour at low
      fraction of disperse phase ratio as opposed to viscoelastic and pseudoplastic
      behaviour at high fraction of disperse phase. Disappearance and spreading
      behaviour of hydrophilic radioactive markers, aprotinin (6512 g/mol) and
      pertechnetate (193 g/mol) entrapped in w/o emulsions from an i.m. injection site
      was studied by whole body gamma-scintigraphy. The retention of entrapped
      aprotinin 24 h postinjection was 83 +/- 5% for a low spreading emulsion and 76 +/
      6% for a high spreading emulsion. The corresponding values for pertechnetate
      were 50 +/- 11 and 23 +/- 2%, respectively. The relatively long retention times
      were suggested to be related to the good physical stability properties of the
      present emulsions. It was concluded that the presented w/o emulsions are
      promising vehicles for sustained release of hydrophilic drugs from an i.m.
      injection site.

PMID- 11250089
TI  - Crystallization of paracetamol from solution in the presence and absence of
      impurity.
AB  - The bulk crystallization of paracetamol has been examined under controlled
      conditions in the presence and absence of the additive p-acetoxyacetanilide
      (PAA), as a function of both supersaturation and additive levels. The induction
      time to nucleation was found to increase with increase in PAA concentration in
      solution. The product micro-crystals were characterized for shape and
      strain/defect content using electron and optical microscopy and X-ray Laue
      diffraction techniques, respectively. A change in crystal habit of the pure
      crystals from columnar (dominant [110]) to plate-like (dominant [001]) was
      observed to occur with an increase in supersaturation level, whilst the addition
      of PAA invariably led to the development of columnar crystals with an aspect
      ratio that varied with impurity level and supersaturation. HPLC showed the PAA to
      be incorporated into the crystals with an average segregation coefficient of 14
      18% depending on the supersaturation. The ready incorporation of PAA is
      attributed to the molecular similarity of this molecule to that of the host
      material. The incorporation is shown to cause a significant increase in the
      mosaic spread, implying the development of a significant strain/defect content in
      the crystals. The influence of the impurity on the time to nucleation is probably
      due to its effect in blocking the development of the critical nucleus. The
      potential implications of such variations in morphology and strain content in the
      design of the physical and chemical properties of the resulting particulates are
      discussed.

PMID- 11250091
TI  - Comparison of human skin or epidermis models with human and animal skin in in
      vitro percutaneous absorption.
AB  - For the study of in-vitro skin penetration of candidate drugs, excised animal
      skin is frequently used as a replacement for human skin. Reconstructed human skin
      or epidermis equivalents have been proposed as alternatives. We compared the
      penetration properties of human, pig and rat skin with the Graftskin LSE (living
      skin equivalent) and the Skinethic HRE (human reconstructed epidermis) models
      using four topical dermatological drugs (salicylic acid, hydrocortisone,
      clotrimazole and terbinafine) with widely varying polarity. In agreement with
      published data, pig skin appeared as the most suitable model for human skin: the
      fluxes through the skin and concentrations in the skin were of the same order of
      magnitude for both tissues, with differences of at most two- or fourfold,
      respectively. Graftskin LSE provided an adequate barrier to salicylic acid, but
      was very permeable for the more hydrophobic compounds (e.g. about 900-fold higher
      flux and 50-fold higher skin concentrations of clotrimazole as compared to human
      skin), even more than rat skin. In the case of the Skinethic HRE, we found
      similar concentrations of salicylic acid as in human skin and an approximately
      sevenfold higher flux. In contrast, the permeation of hydrophobic compounds
      through the epidermal layer was vastly higher than through split-thickness human
      skin (up to a factor of about 800). To conclude, currently available
      reconstituted skin models cannot be regarded as generally useful for in-vitro
      penetration studies.

PMID- 11250090
TI  - A simple method for preparation of immuno-magnetic liposomes.
AB  - A simple and readily manoeuverable method for preparing immuno-magnetic liposomes
      that indigenously contain binding sites for attaching other molecules like
      antibodies on their exterior surface is described. In this method magnetic
      unilamellar vesicles are prepared from a mixture of phosphatidylcholine,
      cholesterol, small amounts of a linear chain aldehyde and colloidal particles of
      magnetic iron oxide, using a reverse phase evaporation technique. The aldehyde
      (dedecanal) molecules align themselves among the lipid molecules in the bilayer
      with their aldehyde groups exposed to the aqueous phase, allowing straight
      attachment of antibody molecules (human-antimouse IgG-FITC in this case) in one
      single step. The success of this approach is confirmed by fluorescence microscopy
      as well as binding of the resulting immuno-magnetic liposomes to their
      corresponding target cells.

PMID- 11250092
TI  - Transdermal delivery of methotrexate: iontophoretic delivery from hydrogels and
      passive delivery from microemulsions.
AB  - In vitro assays were performed to investigate the effectiveness of transdermal
      administration of methotrexate (MTX) by iontophoretic delivery from two types of
      hydrogel and passive delivery from two types of microemulsion. Both iontophoretic
      delivery of MTX from hydrogels and passive delivery from microemulsions were more
      effective than passive delivery from aqueous solutions of the drug. In the
      iontophoretic delivery assays, the type of hydrogel used and the concentration of
      the drug in the loading solution had little influence on effectiveness of
      delivery. In the passive delivery assays, we used both water/oil (w/o) and
      oil/water (o/w) microemulsions: effectiveness of delivery was higher from o/w
      systems. At the end of all assays, significant amounts of MTX were detected in
      the skin. These results suggest that both hydrogels and microemulsions may be of
      value for the topical administration of MTX in the treatment of psoriasis.

PMID- 11250093
TI  - Long-term delivery of all-trans-retinoic acid using biodegradable PLLA/PEG-PLLA
      blended microspheres.
AB  - All-trans-retinoic acid (atRA) has been proved to be effective against several
      malignancies in human clinical trials. However, in many patients who were treated
      with atRA, the cancer relapsed after a brief remission. One reason for such
      relapse is that atRA is metabolized by specific P450s that are induced in the
      liver during prolonged atRA treatments. In order to overcome such a drawback of
      atRA, we prepared biodegradable microspheres to provide continuous release of
      atRA for a long period of time. These biodegradable microspheres were prepared by
      poly(L-lactide) (PLLA) and polyethylene glycol (PEG)-PLLA diblock copolymers
      (PLE) in various blending ratios to control the release rate of atRA. As the PLE
      content in microsphere was increased, the density of the hydrophilic PEG block of
      PLE on microsphere surfaces increased and the microspheres were dispersed well in
      PBS without any surfactants. Various release patterns of atRA were obtained
      according to PLE and atRA contents in the microspheres. Especially, the pseudo
      zero-order release profiles were observed for 5 weeks when the contents of PLE
      and atRA in the microspheres were above 4 wt.%.

PMID- 11250094
TI  - Microionization constants: novel approach for the determination of the
      zwitterionic equilibrium of hydroxyphenylalkylamines by photometric titration.
AB  - The record of the formation of the phenolate and the zwitterionic form in the
      course of titration by photometry makes it possible to estimate the tautomeric
      equilibrium, K(Z), between the zwitterionic and the uncharged form of an
      ampholyte, provided that (1) the absorptivity of the phenolate and the
      zwitterionic form are identical and (2) the absorptivities of both forms are
      distinct from the absorptivities of the protonated and the uncharged form. The
      relation between the absorbance and K(Z), the degree of titration and the degree
      of overlapping of the basic and the acid ionization constant is given.

PMID- 11250095
TI  - In vitro skin permeation of estradiol from various proniosome formulations.
AB  - The skin permeation of estradiol from various proniosome gel formulations across
      excised rat skin was investigated in vitro. The encapsulation efficiency and size
      of niosomal vesicles formed from proniosomes upon hydration were also
      characterized. The encapsulation (%) of proniosomes with Span surfactants showed
      a very high value of about 100%. Proniosomes with Span 40 and Span 60 increased
      the permeation of estradiol across skin. Both penetration enhancer effect of non
      ionic surfactant and vesicle-skin interaction may contribute to the mechanisms
      for proniosomes to enhance estradiol permeation. Niosome suspension (diluted
      proniosomal formulations) and proniosome gel showed different behavior in
      modulating transdermal delivery of estradiol across skin. Presence or absence of
      cholesterol in the lipid bilayers of vesicles did not reveal difference in
      encapsulation and permeation of the associated estradiol. The types and contents
      of non-ionic surfactant in proniosomes are important factors affecting the
      efficiency of transdermal estradiol delivery.

PMID- 11250096
TI  - Gel-forming erodible inserts for ocular controlled delivery of ofloxacin.
AB  - A new application of high molecular weight (400 kDa) linear poly(ethylene oxide)
      (PEO) in gel-forming erodible inserts for ocular controlled delivery of ofloxacin
      (OFX) has been tested in vitro and in vivo. Inserts of 6 mm diameter, 20 mg
      weight, medicated with 0.3 mg OFX, were prepared by powder compression. The in
      vitro drug release from inserts was mainly controlled by insert erosion. The
      erosion time scale was varied by compounding PEO with Eudragit L100 (EUD) 17%
      neutralized (EUDNa17) or 71% neutralized (EUDNa71). The insert erosion rate
      depended on the strength of interpolymer interactions in the compounds, and on
      the hydrophilic-hydrophobic balance of compounds. Immediately after application
      in the lower conjunctival sac of the rabbit eyes, the inserts based on plain PEO,
      PEO-EUDNa17 or PEO-EUDNa71 formed mucoadhesive gels, well tolerated by the
      animals; then the gels spread over the corneal surface and eroded. The gel
      residence time in the precorneal area was in the order PEO-EUDNa71 < PEO < PEO
      EUDNa17. Compared to commercial OFX eyedrops, drug absorption into the aqueous
      humor was retarded by the PEO-EUDNa71 inserts, and both retarded and prolonged by
      the PEO-EUDNa17 inserts, while C(max) (maximal concentration in the aqueous) and
      AUC(eff) (AUC in the aqueous for concentrations > MIC) were barely altered by
      either insert type. On the other hand, C(max), AUC(eff) and t(eff) (permanence
      time in the aqueous at concentrations > MIC) were strikingly increased by plain
      PEO inserts with respect to commercial eyedrops (5.25 +/- 0.56 vs. 1.39 +/- 0.05
      microg ml(-1); 693.6 vs. 62.7 microg ml(-1) min; and 290 vs. 148 min,
      respectively). Bioavailability increase has been ascribed to PEO mucoadhesion
      and/or increased tear fluid viscosity.

PMID- 11250097
TI  - Nebulisation of rehydrated freeze-dried beclomethasone dipropionate liposomes.
AB  - Beclomethasone dipropionate (BDP) liposomes were prepared from various lipids,
      dilauroyl phosphatidylcholine (DLPC), dimyristoyl phosphatidylcholine (DMPC),
      dipalmitoyl phosphatidylcholine (DPPC), and hydrogenated soybean
      phosphatidylcholine (Epikuron 200 SH). A lipid with a low transition temperature
      (T(m)) (DLPC) incorporated a higher amount of BDP than lipid with a high T(m).
      The nebulisation of rehydrated freeze-dried BDP liposomes was carried out using a
      Pari LC Plus nebuliser and the generated aerosol characterised by an Andersen
      Cascade Impactor operated at 28.3 l/min. The rehydrated BDP-DLPC liposomes showed
      a higher output (78.3%) and a higher fine particle fraction (FPF) (75.0%) and
      smaller mass median aerodynamic diameter (MMAD) (3.31 microm) than the other
      rehydrated liposome preparations. Liposomes containing lipid with a high T(m)
      (DPPC and Epikuron) underwent aggregation during nebulisation. This was shown by
      the large increase in size of the DPPC liposomes from 15.78 to 47.51 microm and
      the Epikuron liposomes from 5.84 to 46.70 microm.

PMID- 11250098
TI  - Formulation and process optimization to eliminate picking from market image
      tablets.
AB  - A tablet formulation when compressed using market image tooling may cause picking
      of powder. A D-optimal statistical experiment was designed to optimize the direct
      compression formulation and the process to alleviate picking of powder. The
      effects of levels of magnesium stearate, colloidal silicon dioxide (CSD), and
      lubrication time on picking were investigated using original compression tooling.
      These optimization results provided a small robust manufacturing region, hence a
      change in the cut angles of embossed letters and numbers from 70 degrees to 90
      degrees in the modified compression tooling was evaluated. A statistical analysis
      of the data identified a robust manufacturing region that included formulations
      containing magnesium stearate 1-1.25% w/w, CSD 0.1-0.3% w/w, with a lubrication
      time of 5-10 min when compressed using modified compression tooling. The results
      indicate a significant reduction in picking by increasing the cut angles of
      embossed letters and numbers in the modified compression tooling. By evaluating
      interactions between various variables, we demonstrate a concentration dependent
      effect of CSD on the lubrication efficiency of magnesium stearate and
      compactability of microcrystalline cellulose containing formulation. In addition,
      the lubrication efficiency of magnesium stearate is maintained by blending CSD
      with powder blend prior to lubrication with magnesium stearate.

PMID- 11250099
TI  - Complexation with tolbutamide modifies the physicochemical and tableting
      properties of hydroxypropyl-beta-cyclodextrin.
AB  - The physicochemical and tableting properties of hydroxypropyl-beta-cyclodextrin
      (HP-beta-CD) and its tolbutamide (TBM) complex were studied. The kinetics of
      TBM/HP-beta-CD inclusion complex formation in solution were determined by the
      phase solubility method. Solid complexes were prepared by freeze-drying and spray
      drying. Water sorption-desorption behaviour of the materials were studied and
      compacts were made using a compaction simulator. TBM and HP-beta-CD formed 1:1
      inclusion complexes in aqueous solution with an apparent stability constant of 63
      M(-1). HP-beta-CDs and TBM/HP-beta-CD complexes were amorphous whereas the freeze
      dried and spray-dried TBMs were polymorphic forms II and I, respectively.
      Sorption-desorption studies showed that HP-beta-CDs were deliquescent at high
      relative humidities. TBM/HP-beta-CD complexes had slightly lower water contents
      at low relative humidities than the physical mixtures. However, at high
      humidities their water sorption and desorption behaviours were similar to those
      of corresponding physical mixtures, indicating a glass transition of the
      complexed materials. TBM/HP-beta-CD complexes demonstrated a worse compactability
      than similarly prepared HP-beta-CDs or physical mixtures. Also particle
      properties that resulted from these preparation methods affected the
      compactability of the materials. In conclusion, the physicochemical and tableting
      properties of HP-beta-CD were modified by complexation it with TBM.

PMID- 11250100
TI  - The relevance of nitrendipine erythrocyte partitioning for the variability of its
      bioavailability parameters.
AB  - The pharmacokinetic parameters of nitrendipine were determined in 40 healthy male
      volunteers and a very high degree of intersubject variability was observed (CV =
      39-71%). Since the distribution of nitrendipine to erythrocytes could influence
      the overall pharmacokinetic variability the correlation between hematocrit and
      various pharmacokinetic parameters was analyzed, using linear regression. In
      vitro partitioning of nitrendipine to erythrocytes suspended in physiologic
      saline was studied over a range of hematocrit and drug concentration values. The
      correlations of in vivo pharmacokinetic parameters were linear with medium to
      high correlation coefficients (0.65-0.80). The positive correlation between the
      volume of distribution and hematocrit and negative between AUC, C(max) and beta
      parameters indicate that nitrendipine enters and/or is bound to erythrocytes. The
      results of the in vitro erythrocyte partitioning experiments confirm this
      observations as the mean values of partition coefficient to erythrocytes was
      found to be 2.85 +/- 0.17.

PMID- 11250101
TI  - Covalent coupling of asparagus pea and tomato lectins to poly(lactide)
      microspheres.
AB  - Lectin-poly(lactide) microsphere conjugates specifically designed for oral
      administration were prepared and their activity and specificity in presence of
      mucus were characterized. The presence of hydroxyl or amino groups suitable for
      covalent coupling of lectins by the glutaraldehyde method at the surface of the
      microspheres have been ensured by preparing the particles in presence either of
      poly(vinyl alcohol) (PVA) or bovine serum albumin (BSA). Tomato and asparagus pea
      lectins could be covalently attached to these particles (1.0-1.3 mg/m(2) of
      particles). The conjugates demonstrated a 4-10 fold increase in their
      interactions with mucus compared to control particles. Moreover, the sugar
      specificity of the lectins was maintained.

PMID- 11250102
TI  - Inulin glasses for the stabilization of therapeutic proteins.
AB  - Sugar glasses are widely used to stabilize proteins during drying and subsequent
      storage. To act successfully as a protectant, the sugars should have a high glass
      transition temperature (Tg), a poor hygroscopicity, a low crystallization rate,
      and contain no reducing groups. When freeze drying is envisaged as method of
      drying, a relatively high Tg of the freeze concentrated fraction (Tg') is
      preferrable. In this study, whether inulins meet these requirements was
      investigated. Inulins of various degrees of polymerisation (DP) were evaluated.
      Trehalose glass was used as a positive control. It was found that the Tg and the
      Tg' of inulins with a number/weight average DP (DP(n)/DP(w)) higher than 5.5/6.0
      were higher than those of trehalose glass. Furthermore, inulin glasses showed a
      similar hygroscopicity to that of trehalose glass but crystallized less rapidly.
      Less than 6% of the sugar units of inulins with a DP(n)/DP(w) higher than 5.5/6.0
      contained reducing groups. Trehalose contained no reducing groups. Freeze drying
      of an alkaline phosphatase solution without protectant induced an almost complete
      loss of the activity of the protein. In contrast, when inulins with a DP(n)/DP(w)
      higher than 5.5/6.0 or trehalose were used as stabilizer, the activity was fully
      maintained, also after subsequent storage for 4 weeks at 20 degrees C and 0, 45,
      or 60% RH, respectively. The stabilizing capacities of inulin with a lower DP and
      glucose were substantially less pronounced. After storage at 60 degrees C for 6
      days, the activity of freeze dried samples containing inulins with a DP(n)/DP(w)
      higher than 5.5/6.0 was still about 50% whereas the activity of samples
      containing inulin with a lower DP, glucose, or trehalose was completely lost. It
      is concluded that inulins with a DP(n)/DP(w) higher than 5.5/6.0 meet the physico
      chemical characteristics to successfully act as protectants for proteins. The
      stabilizing potential of these inulins was clearly shown using alkaline
      phosphatase as a model protein.

PMID- 11250103
TI  - Gelatin microspheres crosslinked with D,L-glyceraldehyde as a potential drug
      delivery system: preparation, characterisation, in vitro and in vivo studies.
AB  - To overcome the restriction in using crosslinked gelatin in the pharmaceutical
      field, D,L-glyceraldehyde (GAL), a non-toxic crosslinking agent, was proposed.
      Gelatin microspheres crosslinked with different concentrations of GAL (0.5, 1 or
      2%, w/v) and for different time periods (1 or 24 h) were prepared. The effect of
      the preparation variables was evaluated analysing the extent of crosslinking, the
      morphological aspect, the particle size and the swelling behaviour. To evaluate
      the pharmaceutical properties, an antihypertensive drug, clonidine hydrochloride,
      was chosen as drug model and loaded into the microspheres. Either the increase of
      the crosslinker concentration or of the crosslinking time period decreased both
      the swelling and the in vitro drug release processes of the microspheres. After
      the subcutaneous injection, the loaded microspheres crosslinked with the lowest
      GAL concentration (0.5%, w/v) or for the shortest time period (1 h) showed a
      reduction of systolic blood pressure (SBP) similar to that recorded with a
      clonidine hydrochloride solution having the same drug concentration. Instead, the
      microspheres crosslinked for 24 h with concentrations of GAL higher than 0.5%
      (w/v) produced a more gradual and sustained SBP reduction and the
      antihypertensive effect was maintained until 52-72 h. The biocompatibility
      studies showed that the microspheres crosslinked with GAL are well tolerated in
      vivo. These results suggest the potential application of gelatin microspheres
      crosslinked with GAL as a suitable drug delivery system for the subcutaneous
      administration.

PMID- 11250104
TI  - Evaluation of possible reasons for the low phenylalanine ammonia lyase activity
      in cellulose nitrate membrane microcapsules.
AB  - Microencapsulated phenylalanine ammonia lyase (PAL) exhibits a marked reduction
      in activity compared to the activity of the free enzyme in pH 8.5 Tris buffer.
      The purpose of this investigation was to evaluate the contribution of incomplete
      entrapment, the internal environment of cellulose nitrate membrane microcapsules,
      the diffusional barrier of the membrane and the microcapsulation process to the
      low activity of encapsulated PAL. A solution of PAL and 10% w/v hemoglobin was
      incorporated into cellulose nitrate membrane microcapsules. Hemoglobin
      incorporation was used as a surrogate marker of PAL entrapment. Using 14C
      hemoglobin, the encapsulation efficiency was determined to be 70% and suggested
      that incomplete entrapment might partially account for the low activity of
      encapsulated PAL. The effect of the internal environment of the microcapsule (10%
      hemoglobin solution) on PAL activity was evaluated by comparing enzyme activity
      in 10% w/v hemoglobin solution and pH 8.5 Tris buffer. Similar K(M) and V(max)
      values of PAL in the two media indicated that the internal environment of the
      microcapsule did not contribute to the reduction in activity of the encapsulated
      enzyme. The contribution of a membrane diffusional barrier was determined by
      breaking the putative barrier and measuring PAL activity in intact and broken
      microcapsules. Similar activity of PAL in these two conditions is evidence for
      the lack of a diffusional barrier. The effect of the microencapsulation process
      on PAL activity was evaluated by comparing K(M) and V(max) of free and
      encapsulated PAL. Similar K(M) values in these two media suggested that the
      process did not affect the conformation of PAL. However, encapsulated PAL had a
      50% lower V(max) value compared to free PAL, which showed that the
      microencapsulation process deactivated a substantial proportion of the enzyme.

PMID- 11250105
TI  - The complement system enhances the clearance of phosphatidylserine (PS)-liposomes
      in rat and guinea pig.
AB  - In this study, we investigated the contribution of the complement system to the
      biodistribution of phosphatidylserine (PS)-containing liposomes in rat and guinea
      pig. It appeared that the inclusion of PS in the liposome formulation accelerates
      the rate of liposome uptake by liver, resulting in rapid elimination of the
      liposomes from blood circulation. Pretreatment with K76COOH (K76), an anti
      complement agent, decreased the rapid uptake of PS-containing liposomes by guinea
      pig liver, resulting in increasing blood concentration of the liposomes.
      Significant complement-dependent liposome destabilization was observed in vitro
      in both animals, whereas the complement-dependent destabilization in vivo was
      likely only a part of the process of the clearance of the PS-containing
      liposomes. This discrepancy suggests that the rate of complement-dependent
      liposome uptake by liver is much faster than the rate of complement-dependent
      liposome destabilization in vivo. Pretreatment of K76 dramatically inhibited the
      binding of C3 fragments, one of dominant opsonins, to PS-containing liposomes in
      guinea pig under both in vivo and in vitro conditions. This finding suggests that
      the C3 fragments in the system are responsible for the clearance of the PS
      containing liposomes in guinea pig. In rat, in contrast to guinea pig, in vivo
      binding of C3 fragments was not inhibited by K76-pretreatment, while in vitro
      binding was inhibited. This discrepancy may be due to different experimental
      conditions between in vitro and in vivo assay. Nevertheless, based on the
      observations in this study, the complement components are most likely involved in
      the clearance of the PS-containing liposomes in rat. Taken together, the activity
      of PS in enhancing the liposome clearance appears to be mediated by the
      complement components, presumably C3 fragments, in both guinea pig and rat. This
      is a first report showing the mechanism on the hepatic uptake of the PS
      containing liposomes in guinea pig.

PMID- 11250106
TI  - Physical properties and stability of two emulsion formulations of propofol.
AB  - We have compared the physical properties of two commercial emulsion formulations
      of the intravenous anaesthetic propofol, (Diprivan, AstraZeneca, and Propofol
      Intravenous Emulsion, Gensia Sicor Pharmaceuticals) which appear to differ
      primarily in the additive content and formulation pH. Diprivan contains disodium
      edetate and has a pH of 7-8.5, while the Gensia product contains sodium
      metabisulphite and is formulated to a pH of 4.5-6.4. The average zeta potential
      of Diprivan at pH 8 was -50 mV while that of the Gensia product at pH 4-5 was -40
      mV. This information suggests that the physical stability of Propofol Intravenous
      Emulsion should be lower than that of Diprivan. Three random batches of both
      products were subjected to a range of stability tests, including shaking, thermal
      cycling, and freeze-thaw cycling, and the emulsion droplet size distribution was
      then assessed by dynamic light scattering, light diffraction, and electrical and
      optical zone sensing. Both emulsions initially showed narrow submicrometre
      particle size distributions. An increased level of droplets larger than 5 microm
      could be detected in Propofol Intravenous Emulsion after as little as 4 h shaking
      (300 strokes/min at room temperature) and visible free oil could be detected
      after 8-12 h shaking. In contrast, Diprivan showed no increase in the large
      droplet count after shaking for times up to 16 h. A similar difference in the
      emulsions was found after one freeze-thaw cycle, with Propofol Intravenous
      Emulsion exhibiting extensive coalescence, while that of Diprivan was at the
      limits of detection. We conclude that these two products have different physical
      stability characteristics, and that this may in part be due to the reduced zeta
      potential in Propofol Intravenous Emulsion compared to that of Diprivan.

PMID- 11250107
TI  - Effects of initial particle size on the tableting properties of L-lysine
      monohydrochloride dihydrate powder.
AB  - L-lysine monohydrochloride (LMH) dihydrate was crystallized and the resulting
      powder was sieved to obtain various size fractions. The influence of other
      factors, such as crystallinity and crystal shape, was minimized by using the same
      batch of crystals. Compression of smaller particles at low compaction pressures
      resulted in tablets of greater porosity. The differences in porosity decreased
      with increasing compaction pressure. At the same compaction pressure, smaller
      particles formed tablets of greater tensile strength. However, fragmentation of
      the larger particles tended to equalize the particle size and reduce its
      influence. The differences were reduced for particles larger than 710 microm. For
      crystals of all size fractions, tensile strength increased with increasing
      compaction pressure. The tensile strength increased more rapidly for smaller
      crystals. Tensile strength decreased exponentially with increasing porosity for
      all fractions. The dependence of tensile strength on porosity is explained in
      term of tablet structure. Yield strength, calculated from 'out-of-die' Heckel
      analysis, increased with increasing particle size.

PMID- 11250108
TI  - The effects of terpene enhancers on the percutaneous permeation of drugs with
      different lipophilicities.
AB  - Four model drugs were selected based on their lipophilicity denoted as log P
      (nicardipine hydrochloride log P -0.99 +/- 0.1, hydrocortisone log P 1.43 +/-
      0.47, carbamazepine log P 2.67 +/- 0.38, and tamoxifen log P 7.87 +/- 0.75). The
      enhancing activities of four terpene enhancers (fenchone log P 2.13 +/- 0.30,
      thymol log P 3.28 +/- 0.20, D-limonene log P 4.58 +/- 0.23, and nerolidol log P
      5.36 +/- 0.38) were tested in vitro across full thickness hairless mouse skin
      with each of the evaluated drugs formulated in hydroxypropyl cellulose gel
      formulations. The relationships between lipophilicity (log P) of the terpene
      enhancers and model drugs and efficacy (represented by the enhancement ratio of
      flux ER(flux)) of the drugs when coadministered with the enhancers were examined
      using linear regression. Terpene enhancers had significant effect on the
      percutaneous permeation of the model drugs. Nerolidol (highest lipophilicity)
      provided the highest increase in the flux of the evaluated model drugs. The flux
      of nicardipine hydrochloride increased by approximately 135-fold, hydrocortisone
      by 33-fold, carbamazepine 8-fold, and tamoxifen 2-fold. The lowest increase in
      the flux was observed with fenchone. Linear relationships were generated between
      the ER(flux) of nicardipine hydrochloride, hydrocortisone, carbamazepine, and
      tamoxifen and the log P of the terpene enhancers [r = 0.951, (P = 0.049), r =
      0.977, (P = 0.023), r = 0.942, (P = 0.057), and r = 0.874, (P = 0.126),
      respectively]. Furthermore, the four terpene enhancers produced linear
      relationships, indicating that they were more effective at enhancing the
      penetration of hydrophilic drugs rather than lipophilic drugs r=-0.824 (P=0.176)
      for fenchone, r = -0.891 (P = 0.109) for thymol, r = -0.846 (P = 0.154) for
      limonene, and r = -0.769 (P = 0.232) for nerolidol.

PMID- 11250109
TI  - Lipid extraction and iontophoretic transport of leuprolide acetate through
      porcine epidermis.
AB  - The purpose of this study was to explore the effect of lipid extraction by the
      simple alkyl acetates of increasing carbon chain lengths (e.g. methyl, ethyl,
      propyl, butyl, pentyl, hexyl, and octyl acetates) and iontophoresis on the in
      vitro transport of leuprolide acetate through porcine epidermis. The extent of
      lipid extraction from the stratum corneum (SC) by alkyl acetates was studied by
      Fourier transform infrared (FT-IR) spectroscopy. Ethyl, propyl, pentyl, hexyl,
      and octyl acetates significantly increased (P < 0.05) the permeability of
      leuprolide acetate through the epidermis in comparison to the control (epidermis
      without alkyl acetate treatment). Iontophoresis further increased (P < 0.05) the
      permeability of leuprolide acetate for all the alkyl acetates studied, when
      compared to their corresponding passive permeability. Ethyl acetate produced the
      maximum passive (13.47 microg/cm(2)/h) and iontophoretic (89.79 microg/cm(2)/h)
      flux among all the alkyl acetates studied. The SC treated with alkyl acetates
      showed a decrease in peak heights and areas of asymmetric and symmetric C--H
      stretching absorbances in comparison to untreated SC. A greater percentage
      decrease in peak heights and areas was obtained by ethyl acetate.
      Chloroform:methanol(2:1) [C:M(2:1)] was used as a positive control for lipid
      extraction. Our findings provide evidence that alkyl acetates cause lipid
      extraction, which leads to an enhancement in the passive and iontophoretic
      permeability of leuprolide acetate.

PMID- 11250110
TI  - Dehydration behavior of nedocromil magnesium pentahydrate.
AB  - The dehydration of nedocromil magnesium (NM) pentahydrate proceeds in two steps,
      corresponding to the loss of four water molecules in the first step and one water
      molecule in the second step. The effects of temperature, particle size, sample
      weight, water vapor pressure and dehydration-rehydration cycle on both the
      kinetics and activation energy of the dehydration of NM pentahydrate were studied
      using isothermal TGA and temperature-ramp DSC analyzed by Kissinger's method. The
      dehydration kinetics for both steps are best described by the Avrami-Erofeev
      equations, suggesting a nucleation-controlled mechanism. The high activation
      energy for the second dehydration step indicates that the last water molecule,
      which is bonded both to a magnesium ion and to a carboxylate oxygen atom, is more
      'tightly bound'. The activation energy decreased with increasing sample weight
      and decreasing particle size. The dehydration rate increased with decreasing
      water vapor pressure and with repetition of the dehydration-hydration cycle.
      Dynamic and isothermal PXRD, and 13C solid-state NMR were employed to provide an
      insight into the dehydration mechanism and the nature of solid-state phase
      transformation during the dehydration. Molecular modeling with Cerius(2) was used
      to visualize the crystal structure and to construct the molecular packing
      diagram. A correlation was noted between the dehydration behavior and the bonding
      environment of the water molecules in the crystal structure.

PMID- 11250111
TI  - Transport of poly amidoamine dendrimers across Madin-Darby canine kidney cells.
AB  - The objective of this study was to determine the permeability of a series of poly
      amidoamine (PAMAM) dendrimers of generations 0-4 (G0-G4) across MDCK (Madin-Darby
      Canine Kidney) cell line. PAMAM dendrimers with incremental increase in size and
      molecular weight were labeled by fluorescein isothiocyanate (FITC) and the least
      polydisperse fractions were collected by size exclusion chromatography. MDCK
      cells were grown on Transwell filters for four days. The conjugates were detected
      by HPLC equipped with fluorescence detector. The permeability of the dendrimers
      across MDCK cells was determined in the apical to basolateral direction. The rank
      order permeability of the PAMAM dendrimers was G4 >> G1 approximately G0 > G3 >
      G2. The permeability of mannitol in the presence of G4 increased by nine-fold.
      Results suggest that the transepithelial transport of PAMAM dendrimers is
      effected by both the polymer size, and the modulation of the cell membrane by the
      cationic dendrimers.

PMID- 11250112
TI  - Experimental gerontology in the Nordic countries.
AB  - Research in geriatric medicine developed in the Nordic countries in the 1950s,
      following the tradition from the United Kingdom. Quite early, longitudinal
      epidemiological studies of 'normal' ageing emerged. Now there are chairs in
      geriatric medicine at many of the medical schools. Experimental gerontology came
      much later, typically scattered in a variety of medical school departments. There
      is only one chair in gerontology (in Tampere). Two major research undertakings
      have emerged in recent years, the Danish Centre for Molecular Gerontology, and a
      cluster of research groups at the Division of Geriatrics at the Karolinska
      Institutet. Other research groups are found in Denmark at the universities in
      Aarhus, Copenhagen and Odense; in Finland at the universities in Jyvaskyla,
      Kuopio, Tampere and Turku; and in Norway at the university in Trondheim. These
      activities are reviewed country-wise.

PMID- 11250113
TI  - Support for basic gerontological research in the USA.
AB  - Support for research in basic gerontology in the United States of America is
      briefly described. The support mechanisms, how to apply for a grant, and priority
      areas of research are outlined, and recent progress in a few of these priority
      areas is discussed. In general, government support for biogerontology research
      has been generous, and as a result considerable progress has been made in
      understanding the molecular mechanisms of aging in animal model systems.
      Translation of these findings to humans, and development of interventions to
      promote healthy aging in humans remain an unfulfilled priority, but new knowledge
      and development of better technologies and model systems suggest an optimistic
      future.

PMID- 11250114
TI  - Sex and ageing.
AB  - Sex and ageing are often linked, particularly in the context of the evolutionary
      theories of ageing, which suggest that senescence may be the price for investing
      in offspring at the expense of somatic maintenance and repair. Considerable
      evidence supports this concept although, strictly, it is not sex per se but the
      existence of the soma/germ-line distinction that appears to hold the key. Other
      aspects of the sex-ageing axis seeing exciting new developments are the evolution
      of the human life history, particularly with respect to menopause, and the
      molecular mechanisms that sustain the immortality of the germ-line in contrast to
      the cumulative damage that appears to underlie the ageing of somatic cells.

PMID- 11250115
TI  - Heterogeneity and its biodemographic implications for longevity and mortality.
AB  - In the visible world, heterogeneity typically refers to the differences that
      exist among individuals in a defined population. These differences can arise from
      a variety of sources--biological, behavioral and social. Ever since Darwin,
      scientists have argued over the biological significance of differences observed
      at the individual, morphological, physiological, genetic, molecular and
      structural levels. A general consensus has been reached. Heterogeneity is
      ubiquitous, it is important, and it increases as observations are made at finer
      levels of biological resolution. Debates over the significance of heterogeneity
      have emerged once again as biologists and demographers work together in order to
      create the emerging field of biodemography. For these scientists, the debates
      center around the relative impact that individual heterogeneity has on population
      level statistics. It is argued here that in a world where the mortality barriers
      to long life for individuals have been dramatically weakened, the population
      consequences of heterogeneity are already visible and will grow in importance as
      biomedical technologies continue to usher progressively more people into the post
      reproductive period of the lifespan.

PMID- 11250116
TI  - Comparative demography of isogenic populations of Caenorhabditis elegans.
AB  - Demographic characteristics of the bacterial-feeding nematode Caenorhabditis
      elegans were determined in two long-lived mutant strains, TJ1052 (age-1), CB4876
      (clk-1), and a wild-type strain, N2. Within each strain, there was little
      correlation between longevity and reproduction for individuals that lived longer
      than 10days. Long-lived mutant strains produced fewer eggs than the wild type.
      Mean total life spans were 13.2days for the wild type, 21.9days for age-1, and
      15.8days for clk-1; maximum life spans were 24days for the wild type, 47days for
      age-1, and 32days for clk-1. Differences in total life span resulted primarily
      from longer post-reproductive survival. The mean post-reproductive life spans
      were longer than the wild type by 183% in age-1 and 60% in clk-1. We conclude
      that (i) post-reproductive survival is not correlated with egg production within
      isogenic populations of C. elegans, and (ii) the relationship between
      reproduction and longevity differs among isogenic populations with specific
      longevity genes.

PMID- 11250117
TI  - Antioxidant status and stress resistance in long- and short-lived lines of
      Drosophila melanogaster.
AB  - The purpose of this study was to understand the nature of the biochemical and
      physiological variations between genetically different lines of Drosophila
      melanogaster. Selection for early or delayed reproduction has given rise to lines
      with substantial and heritable differences in longevity. The hypotheses tested
      were that either: (i) a compensatory slowing of metabolism, (ii) increased
      antioxidative enzyme activities, or (iii) elevated resistance to stressful
      conditions underlie these differences in longevity. The metabolic rate, metabolic
      potential (i.e. total amount of oxygen consumed during average lifespan) and
      speed of walking were all greater in long-lived than in short-lived flies, but
      there was no enhancement of antioxidant defenses. In fact, catalase activity was
      significantly lower in the long-lived flies. Long life was largely maintained
      under heat stress and starvation conditions, and was maintained to a lesser
      extent upon exposure to paraquat, a superoxide radical generator. In contrast,
      the 'short-lived' flies had a longer lifespan under cold stress and hyperoxia,
      also an inducer of radical generation. These results contradict the first two
      hypotheses and suggest that alleles underlying either long or short life are
      linked with enhanced resistance to specific kinds of stress, which may account
      for the preservation of these alleles in the parental population.

PMID- 11250118
TI  - Induction of senescence-associated genes by 5-bromodeoxyuridine in HeLa cells.
AB  - 5-Bromodeoxyuridine (BrdU) universally induces a senescence-like phenomenon in
      mammalian cells. To assess this phenomenon at the level of gene expression, we
      constructed a PCR-based subtractive cDNA library enriched for mRNA species that
      immediately increase by administration of BrdU to HeLa cells. Candidate cDNA
      clones were isolated by differential colony hybridization, and then positive
      clones were identified by Northern blot analysis. Sequencing analysis revealed
      that the identified cDNA species were classified into three groups: widely used
      senescence-markers, known species whose relevance to senescence is yet to be
      reported, and known or novel ESTs. As expected, the majority of them showed an
      increase in expression in senescent human diploid fibroblasts. These results
      suggest that similar mechanisms operate in the regulation of BrdU-induced genes
      and senescence-associated genes.

PMID- 11250119
TI  - Lipofuscin accumulation in proliferating fibroblasts in vitro: an indicator of
      oxidative stress.
AB  - The amount of the ageing pigment, lipofuscin, found in replicating cells depends
      both on its rate of formation as well as its rate of dissolution by cell
      division. We present a model which allows the calculation of the lipofuscin
      accumulation rate from measurements of its amount and of the cell cycle duration.
      In two human fibroblast strains, the accumulation rate correlates well with
      differences in oxidative stress/antioxidative defence as measured by
      intracellular peroxide generation, protein carbonyl content, telomere shortening
      rate and replicative life span. The lipofuscin content increases with replicative
      age in both cultures. The rather steep increase in presenescent fibroblasts is
      not solely due to a slowing down of the cell turnover, but is partially caused by
      an increased rate of lipofuscin formation/ accumulation. This might indicate an
      increased level of oxidative stress in presenescent fibroblasts, or a decreased
      efficiency of proteolytic systems, or both. The results are in accordance with
      data demonstrating an adverse effect of lipofuscin accumulation on cellular
      protein turnover and suggest an active role for lipofuscin accumulation in
      cellular senescence.

PMID- 11250120
TI  - Two-dimensional gel electrophoretic studies on the cellular aging: accumulation
      of alpha-2-macroglobulin in human fibroblasts with aging.
AB  - To understand the mechanisms that control life span and age-related phenotypes,
      we used two-dimensional (2D) gel electrophoresis to study the intracellular
      proteins whose amounts change during the process of cellular aging. We found that
      the amount of an alpha-2-macroglobulin (A2M) fragment derived from culture medium
      increased in the cells with aging. A2M is linked to Alzheimer's disease both
      genetically and functionally. This is the first report of accumulation of an A2M
      fragment in senescent fibroblasts. We also studied 2D gel profiles of human
      fibroblasts immortalized by treatment with either 60Co gamma rays or 4
      nitroquinoline 1-oxide. As immortalized cells overcome cellular senescence to
      gain an unlimited life span, the proteins whose amounts change after
      immortalization may be relevant to the age-related phenotypes. 2D gel analysis
      revealed that the A2M fragment was down-regulated in the immortalized cells,
      compared with their normal counterparts, regardless of their passage. We also
      found that the other four proteins increased in amount with aging and decreased
      in amount after immortalization. Our results suggest: (1) the A2M incorporation
      into the cells is increased in the process of cellular aging; and (2) A2M may be
      linked to the age-related phenotypes that were lost during the process of
      immortalization of human cells.

PMID- 11250121
TI  - The protection of rat liver autophagic proteolysis from the age-related decline
      co-varies with the duration of anti-ageing food restriction.
AB  - Restricting caloric intake (CR) well below that of ad libitum (AL) fed animals
      retards and/or delays many characteristics of ageing and the occurrence and
      progression of age-associated diseases, efficacy depending on duration. The
      hypothesis that the anti-ageing effect of CR might involve stimulation of the
      cell-repair mechanism autophagy was tested. The effects of ageing and duration of
      anti-ageing CR on liver autophagic proteolysis (AP) were explored in male AL
      Sprague-Dawley rats aged 2-, 6-, 12- and 24-months; and 24-month-old rats on a CR
      diet initiated at 2-, 6- and 12-month of age or initiated at age 2-months and
      interrupted at age 18 months. The age-related changes in the regulation of AP
      were studied by monitoring the rate of valine release in the incubation medium
      from isolated liver cells by an HPLC procedure. Results show that the maximum
      attainable rate and the regulation of AP decline with increasing age; that
      changes are prevented by anti-ageing CR initiated at young age, that the
      protective effects of CR change with the duration of diet. It is concluded that
      the data are compatible with the hypothesis that AP and improved membrane
      maintenance might be involved in the antiageing mechanism of CR.

PMID- 11250122
TI  - Age-related changes in the urinary excretion of aldehydes in ad libitum fed and
      food-restricted rats.
AB  - Age-related changes in the urinary excretion of aldehydes arising from lipid
      peroxidation have been investigated in male Sprague-Dawley rats aged 2, 4, 6, 12,
      18, 24 and 27 months, fed ad libitum or subjected to two different regimens of
      calorie restriction (namely every-other-day ad libitum feeding--EOD--and 40%
      calorie restriction--40%DR). For only some age groups, results were compared with
      those obtained in ad libitum fed male Fisher 344 and Lewis rats. Results show
      that the urinary excretion of malondialdehyde (MDA) and formaldehyde (FA)
      significantly decreases, whereas that of propionaldehyde (PROP) progressively
      increases with age, and that urinary excretion of acetaldehyde (ACT) does not
      show any significant age-related variations. Dietary restriction significantly
      increases the urinary levels of MDA, FA and PROP without affecting their age
      related modifications, and does not affect ACT urinary excretion. In conclusion,
      results indicate that the quantitative pattern of aldehyde production and urinary
      excretion may be altered by the process of aging.

PMID- 11250123
TI  - Diminished percentage of antigen bearing cells in the lymph nodes of immune aged
      rats.
AB  - We have demonstrated previously that during experimental autoimmune prostatitis
      (EAP), aged rats show a diminished humoral autoimmune response. In the present
      paper we have studied the transport of the autoantigen from the site of injection
      toward lymphatic organs in rats of different ages with or without EAP. We used as
      autoantigen prostatic components (rat accessory glands (RAG)) conjugated with
      fluorescein isothiocyanate (FITC). Studies of flow cytometry, fluorescent
      microscopy and confocal microscopy show no differences in the percentage of RAG
      FITC positive cells or in the localization of the cells in the popliteal lymph
      nodes of not-immunized young and aged rats. On the other hand, in 18-month-old
      rats immunized with either RAG or Ovalbumin there were lower levels of specific
      IgG antibodies and fewer antigen containing cells in the draining lymph nodes
      than those of 3- or 12-month-old rats. In all groups fluorescent cells were MHC
      class II positive and some were IgM positive. Our results demonstrate that in
      immunized 18-month-old rats there is a diminished percentage of cells bearing the
      antigen in the draining lymph nodes after antigen injection in the skin, related
      to the levels of specific antibodies able to form antigen-antibody complexes in
      the periphery.

PMID- 11250124
TI  - The progression of chronic tuberculosis in the mouse does not require the
      participation of B lymphocytes or interleukin-4.
AB  - The aging process is associated with alterations in the immune system. Some of
      the changes reported are an increase in the proportion of B lymphocytes, and a
      shift to a TH2-like cytokine environment. It has been hypothesized that the
      development of immunopathology within the lung during tuberculosis is linked to
      increased interleukin-4 (IL-4) production. In addition, a role for B cells in
      maintaining granuloma integrity has been recently proposed. This study
      investigated the role of B cells and IL-4 during the long-term course of chronic
      tuberculosis in mice and showed that the course of Mycobacterium tuberculosis
      infection in the lungs was not influenced by the absence of B lymphocytes or the
      TH2 cytokine IL-4.

PMID- 11250125
TI  - Serum interleukin-6, soluble interleukin-6 receptor and soluble gp130 exhibit
      different patterns of age- and menopause-related changes.
AB  - Growing evidence suggests that interleukin-6 (IL-6) may play a pathogenetic role
      in postmenopausal bone loss and in other age-related pathological conditions. In
      this study, we have examined the age-related changes in the serum levels of IL-6
      and the soluble receptors that modulate its biological activity--soluble IL-6
      receptor (sIL-6R) and soluble gp130 (sgp130)--in 220 women (from 25 to 104yr
      old), including 22 centenarians. Serum IL-6 rose exponentially with age (r=0.74,
      p<0.0001). The median level of IL-6 increased almost ten-fold with age, from
      1.16pg/ml in premenopausal women to 10.27pg/ml in centenarians. Serum sIL-6R and
      sgp130 showed an increase until the seventh decade and a progressive decrease in
      older ages (r=0.39, p<0.0001 and r=0.26, p=0.008, respectively). IL-6, sIL-6R and
      sgp130 were significantly higher in women within 10yr of menopause as compared to
      premenopausal subjects (1.51 vs. 1.16pg/ml, p=0.012; 41.9 vs. 35.7ng/ml, p=0.002;
      and 253.4 vs. 230.7ng/ml, p=0.008, respectively). In postmenopausal women, a
      negative correlation was found between sIL-6R and the lumbar bone mineral density
      (BMD) (r=-0.28, p=0.002) even after adjusting for age and weight. Furthermore,
      sIL-6R levels were higher in osteoporotic compared to normal women (47.9 vs.
      39.5ng/ml, p=0.001). In conclusion, our results show that the serum levels of IL
      6, sIL-6R and sgp130 exhibit different patterns of age- and menopause-related
      changes, and that the biological activity of IL-6 may be increased with age with
      potential implications in the age-related diseases such as osteoporosis.

PMID- 11250126
TI  - Interleukin-1beta induced cyclooxygenase 2 expression and prostaglandin E2
      secretion by human neuroblastoma cells: implications for Alzheimer's disease.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) may decrease the risk of
      developing Alzheimer's disease (AD). Cyclooxygenase 2 (COX-2), one of the targets
      of NSAIDs, is increasingly expressed in neuronal cells in AD brain. In this
      study, of the cytokines that are found at increased levels in AD brain
      (interleukin (IL)-1alpha, IL-1beta, IL-6 and tumour necrosis factor (TNF)alpha),
      IL-1beta was found to induce COX-2 immunoreactivity and prostaglandin (PG) E2
      secretion by human neuroblastoma cell line SK-N-SH. COX inhibitors indomethacin
      and BF389, as well as the glucocorticoid dexamethasone (DEX) and
      pyrrolidinedithiocarbamate, which is an inhibitor of nuclear factor kappaB as
      well as a potent antioxidant, inhibited IL-1beta induced PGE2 secretion. In
      addition, DEX reduced the IL-1beta induced COX-2 immunoreactivity in the same
      concentration as wherein it inhibited PGE2 secretion. Palmitoyl trifluormethyl
      ketone, an inhibitor of Ca(2+) independent phospholipase A2 (iPLA2) and a less
      potent inhibitor of cytosolic PLA2, dose-dependently reduced the IL-1beta induced
      PGE2 secretion. This suggests that the IL-1beta induced PGE2 secretion may depend
      on the availability of arachidonic acid. Although the physiological role of
      neuronal COX-2 still remains unclear, we suggest an interplay between glial
      derived IL-1 and neuronal upregulation of COX-2 expression in chronic
      neurodegenerative diseases, such as AD.

PMID- 11250127
TI  - Haemoconcentration, shear-stress increase and carotid artery diameter regulation
      after furosemide administration in older hypertensives.
AB  - The aim of the present study was to determine whether changes of carotid wall
      shear stress induced by changes in blood viscosity after diuretic administration
      cause carotid arterial dilatation in elderly hypertensives, as reported in the
      cat. Arterial wall shear rate (ultrasound technique, profilmeter FRP III), the
      systo-diastolic diameter (echotracking technique) and the mean blood flow
      velocity and volume of the common carotid artery, the blood viscosity (rotational
      viscometer) and the finger arterial blood pressure (Finapress Ohmeda) were
      measured in 12 young volunteers (aged 25+/-2 years) and in 12 elderly
      hypertensives (aged 80+/-4 years) treated with short-acting calcium antagonists
      up to 24h before the study, both at baseline and after intravenous furosemide
      infusion (0.5mg/min), when the haematocrit had increased by at least two
      percentage points. After furosemide administration the mean arterial blood
      pressure decreased and blood viscosity and carotid systolic shear stress
      increased in both groups. However, common carotid artery diameter increased only
      in the young controls but not in the elderly hypertensives. These data show that
      an increase in carotid shear stress caused by haemoconcentration induces carotid
      vasodilatation only in young healthy subjects, and not in elderly hypertensives.
      This effect may be related to impaired endothelium function and/or arterial wall
      mechanics.

PMID- 11250131
TI  - Chromosomes and expression mechanisms. Web alert.

PMID- 11250128
TI  - Analysis of lymphocyte diversity in the elderly: heteroduplex analysis and
      alternative techniques.
AB  - Heteroduplex analysis allows global analysis of T cell receptor clonality. This
      review outlines the method, compares it to other available techniques for the
      study of clonality and reviews current literature on how these are being used to
      investigate alterations in the T cell repertoire within elderly individuals.

PMID- 11250133
TI  - Nucleosomes and the chromatin fiber.
AB  - During the past year and a half, significant progress has been made in
      understanding the structure and dynamics of nucleosomes and the chromatin fiber,
      the mechanism of action of the core histone amino termini, the structure and
      function of histone variants, and the function of linker histones in the
      chromatin fiber.

PMID- 11250134
TI  - Higher-order structure of chromatin and chromosomes.
AB  - The linear array of nucleosomes that comprises the primary structure of chromatin
      is folded and condensed to varying degrees in nuclei and chromosomes forming
      'higher order structures'. We discuss the recent findings from novel experimental
      approaches that have yielded significant new information on the different
      hierarchical levels of chromatin folding and their functional significance.

PMID- 11250135
TI  - The ins and outs of nucleosome assembly.
AB  - De novo nucleosome assembly coupled to DNA replication and repair in vitro
      involves the histone chaperone chromatin assembly factor 1 (CAF-1). Recent
      studies support a model in which CAF-1 can be targeted to newly synthesized DNA
      through a direct interaction with proliferating cell nuclear antigen (PCNA) and
      can act synergistically with a newly identified histone chaperone. Insights have
      also been obtained into mechanisms by which this CAF-1-dependent pathway can
      establish a repressed chromatin state.

PMID- 11250136
TI  - Transcription and chromatin converge: lessons from yeast genetics.
AB  - The control of transcription through the modification of chromatin has been a
      subject of intense study over the past year. The increasing use of genome-wide
      approaches to examine the role of chromatin and the complexes able to modify it
      is providing a global perspective that is profoundly altering our view of the
      transcription process.

PMID- 11250137
TI  - Mechanisms for ATP-dependent chromatin remodelling.
AB  - During the past year, major advances have been made towards understanding the
      function of ATP-dependent chromatin-remodelling activities both in vitro and in
      vivo. These suggest that ATP-dependent chromatin-remodelling activities are
      capable of both altering the structure of individual nucleosomes and acting in
      concert with other forms of chromatin-modifying enzymes, to regulate the
      formation and decondensation of chromatin fibres.

PMID- 11250138
TI  - Histone acetyltransferases: function, structure, and catalysis.
AB  - Histone acetyltransferases (HATs) directly link chromatin modification to gene
      activation. Recent structure/function studies provide insights into HAT catalysis
      and histone binding, and genetic studies suggest cross-talk between acetylation
      and other histone modifications. Developmental aberrations in mice and certain
      human cancers are associated with HAT mutations, further highlighting the
      importance of these enzymes to normal cell growth and differentiation.

PMID- 11250139
TI  - Functional significance of histone deacetylase diversity.
AB  - Nucleocytoplasmic shuttling of histone deacetylases is emerging as a major step
      in determining the composition, and hence the activity, of the corresponding
      nuclear regulatory complexes. This shuttling process is one of the distinctive
      characteristics of these enzymes, themselves belonging to structurally and
      functionally different classes. Considering the specific features of each class
      of deacetylases, it is possible to determine how each member can contribute to
      particular cellular functions.

PMID- 11250140
TI  - Chromatin remodeling in development and differentiation.
AB  - During development and differentiation, early inductive processes that influence
      cell fate at a later stage leave marks at distinct gene loci that are maintained
      through several rounds of mitosis. The structure of chromatin is part of this
      epigenetic memory that restricts or permits differential expression of genes in
      descendant cells. Establishing a cell-type-specific chromatin pattern thus
      predestines future cell differentiation and deters cell-lineage infidelity, as it
      often occurs during neoplastic transformation. As such, understanding the
      dynamics and mechanisms underlying chromatin remodeling has been a major focus of
      recent molecular genetic research that holds great promise for biomedical
      discoveries.

PMID- 11250141
TI  - The Polycomb group--no longer an exclusive club?
AB  - Polycomb group (PcG) proteins maintain silencing at target loci in higher
      eukaryotes but recent evidence suggests that about half of these proteins are
      also required for maintenance of activation at homeotic loci. We suggest that PcG
      and trithorax group response elements should acquire a new name, 'maintenance
      elements', to reflect the dual function of regulatory elements that bind both
      groups of proteins. New data suggest that there might be a functional link
      between PcG repression and cell-cycle regulation.

PMID- 11250142
TI  - A solid foundation: functional specialization of centromeric chromatin.
AB  - Centromeres provide a distinctive mechanical function for the chromosomes as the
      site of kinetochore assembly and force generation in mitosis and meiosis. Recent
      studies show that a unique form of chromatin, based on the histone-H3-like
      protein CENP-A and homologues, provides a conserved foundation for this
      mechanical chromatin domain. CENP-A plays a role in templating kinetochore
      assembly and may be a central element in the epigenetic maintenance of centromere
      identity. Cohesion at the centromere, intimately linked to kinetochore assembly,
      is required for integrating spindle forces exerted across the centromere and for
      establishing the bipolar geometry of sister kinetochores.

PMID- 11250143
TI  - Telomeric chromatin: replicating and wrapping up chromosome ends.
AB  - Recent advances in our understanding of the specialized chromatin structure at
      telomeres, the ends of eukaryotic chromosomes, have focused on three separate
      areas: replication of telomeres through the coordinated action of conventional
      DNA polymerases and the telomerase enzyme, protection of the chromosome end from
      DNA damage checkpoint sensors and DNA-repair processes, and the discovery of a
      novel deacetylase enzyme (Sir2p) required for the establishment and maintenance
      of telomeric heterochromatin. Although the number of proteins and the complexity
      of their interactions at telomeres continues to grow, a picture of at least some
      of the major players and mechanisms underlying telomere replication, end
      'capping' and chromatin assembly is beginning to emerge.

PMID- 11250144
TI  - Chromosomal boundaries in S. cerevisiae.
AB  - Chromatin boundary elements or insulators in metazoans delimit distinct
      chromosomal domains of gene expression. Recently, DNA sequences with properties
      similar to boundary elements were also discovered in Saccharomyces cerevisiae.
      These sequences block the spread of transcriptionally silent chromatin, the yeast
      equivalent of metazoan heterochromatin, and are referred to as 'heterochromatin
      barriers'. These barriers share no sequence homology but all consist of multiple
      binding sites for various regulatory proteins. Current data suggest that barriers
      may function in yeast by recruiting a protein complex that precludes nucleosome
      assembly and thereby disrupts a contiguous array of nucleosomes required for the
      spread of silent chromatin.

PMID- 11250145
TI  - Enhanceosomes.
AB  - Gene-specific transcriptional regulation in higher eukaryotes is mediated by
      complex cis-acting control elements that specify the location, timing and
      magnitude of the response. During the past five years, an argument has been made
      that in several cases specificity in gene transcription is achieved by the
      assembly of higher-order three-dimensional transcription factor/enhancer DNA
      complexes, termed enhanceosomes. The inherent co-operativity in enhanceosome
      assembly and the embedded synergy in transcription ensure that a specific gene
      would be selected for activation only if all the enhanceosome components are
      present in the same nucleus. Enhanceosomes activate transcription by recruiting
      chromatin-modifying activities and basal transcription factors to the nearby
      promoters.

PMID- 11250146
TI  - Mechanism of transcription initiation and promoter escape by RNA polymerase II.
AB  - Recently, key advances in biochemical and structural studies of RNA polymerase II
      (pol II) and the basal transcriptional machinery have shed considerable light on
      the basic mechanisms underlying the initiation stage of eukaryotic mRNA
      synthesis. The development of methods for obtaining crystal structures of pol II
      and its complexes has revolutionized transcriptional studies and holds promise
      that aspects of initiation will soon be understood at atomic resolution;
      crosslinking studies have revealed intriguing features of the topology of the pol
      II initiation complex and provided working models for dynamic steps of
      initiation; and mechanistic studies have identified promoter escape as a critical
      step during initiation and brought to light novel roles for the general
      initiation factors TFIIE, TFIIF, and TFIIH in this process.

PMID- 11250147
TI  - Epigenetic developmental mechanisms in plants: molecules and targets of plant
      epigenetic regulation.
AB  - Genetic approaches to understanding the role of epigenetic regulation of gene
      expression in plants and its mechanisms have revealed several new components.
      Rapidly accumulating information from other eukaryotes provides complementary
      knowledge with important implications for plant research. Comparison of
      epigenetic events across species is proving critical for defining the mechanisms
      and functions of epigenetic modification, including those specific to plants.

PMID- 11250148
TI  - RNA-based silencing strategies in plants.
AB  - In plants, double-stranded RNA can silence genes by triggering degradation of
      homologous RNA in the cytoplasm and by directing methylation of homologous
      nuclear DNA sequences. Analyses of Arabidopsis mutants and plant viral
      suppressors of silencing are unraveling RNA-silencing mechanisms, which require
      common proteins in diverse organisms, and are assessing the role of methylation
      in transcriptional and posttranscriptional gene silencing.

PMID- 11250149
TI  - An evolutionarily conserved function of the Drosophila insulin receptor and
      insulin-like peptides in growth control.
AB  - BACKGROUND: Size regulation is fundamental in developing multicellular organisms
      and occurs through the control of cell number and cell size. Studies in
      Drosophila have identified an evolutionarily conserved signaling pathway that
      regulates organismal size and that includes the Drosophila insulin receptor
      substrate homolog Chico, the lipid kinase PI(3)K (Dp110), DAkt1/dPKB, and dS6K.
      RESULTS: We demonstrate that varying the activity of the Drosophila insulin
      receptor homolog (DInr) during development regulates organ size by changing cell
      size and cell number in a cell-autonomous manner. An amino acid substitution at
      the corresponding position in the kinase domain of the human and Drosophila
      insulin receptors causes severe growth retardation. Furthermore, we show that the
      Drosophila genome contains seven insulin-like genes that are expressed in a
      highly tissue- and stage-specific pattern. Overexpression of one of these insulin
      like genes alters growth control in a DInr-dependent manner. CONCLUSIONS: This
      study shows that the Drosophila insulin receptor autonomously controls cell and
      organ size, and that overexpression of a gene encoding an insulin-like peptide is
      sufficient to increase body size.

PMID- 11250151
TI  - Control of progenitor cell number by mitogen supply and demand.
AB  - BACKGROUND: Much is known about how cell proliferation is controlled at the
      single cell level, but much less about the control of cell numbers in developing
      populations. Cell number might be determined by an intracellular division limiter
      or, alternatively, by the availability of mitogens or other factors outside the
      cell. We investigated the relative importance of intracellular and extracellular
      controls for one well-defined population of neural precursor cells, namely the
      glial progenitors that give rise to oligodendrocytes in the mouse spinal cord.
      RESULTS: We found by cumulative BrdU labeling in vivo that the progenitor cell
      division cycle slows down markedly as their numbers increase during
      embryogenesis. When cultured in saturating PDGF, the main mitogen for these
      cells, their cell cycle accelerated and was independent of their prior rate of
      division in vivo. This shows that mitogens are limiting in vivo, and suggests
      that division normally slows down because the PDGF concentration declines. In
      PDGF-transgenic mice, cell number was proportional to the PDGF supply and
      apparently unsaturable; at ten times the normal rate of supply, cell number was
      still increasing but the animals were no longer viable. CONCLUSIONS: Progenitor
      cell proliferation in the embryo is limited by environmental factors, not a cell
      intrinsic mechanism. The linear relationship between PDGF supply and final cell
      number strongly suggests that cells deplete the mitogenic activity in their
      environment at a rate proportional to the total number of cells. The cells might
      simply consume the available PDGF or they might secrete autocrine inhibitors, or
      both.

PMID- 11250150
TI  - Two RGS proteins that inhibit Galpha(o) and Galpha(q) signaling in C. elegans
      neurons require a Gbeta(5)-like subunit for function.
AB  - BACKGROUND: Gbeta proteins have traditionally been thought to complex with Ggamma
      proteins to function as subunits of G protein heterotrimers. The divergent
      Gbeta(5) protein, however, can bind either Ggamma proteins or regulator of G
      protein signaling (RGS) proteins that contain a G gamma-like (GGL) domain. RGS
      proteins inhibit G protein signaling by acting as Galpha GTPase activators. While
      Gbeta(5) appears to bind RGS proteins in vivo, its association with Ggamma
      proteins in vivo has not been clearly demonstrated. It is unclear how Gbeta(5)
      might influence RGS activity. In C. elegans there are exactly two GGL-containing
      RGS proteins, EGL-10 and EAT-16, and they inhibit Galpha(o) and Galpha(q)
      signaling, respectively. RESULTS: We knocked out the gene encoding the C. elegans
      Gbeta(5) ortholog, GPB-2, to determine its physiological roles in G protein
      signaling. The gpb-2 mutation reduces the functions of EGL-10 and EAT-16 to
      levels comparable to those found in egl-10 and eat-16 null mutants. gpb-2
      knockout animals are viable, and exhibit no obvious defects beyond those that can
      be attributed to a reduction of EGL-10 or EAT-16 function. GPB-2 protein is
      nearly absent in eat-16; egl-10 double mutants, and EGL-10 protein is severely
      diminished in gpb-2 mutants. CONCLUSIONS: Gbeta(5) functions in vivo complexed
      with GGL-containing RGS proteins. In the absence of Gbeta(5), these RGS proteins
      have little or no function. The formation of RGS-Gbeta(5) complexes is required
      for the expression or stability of both the RGS and Gbeta(5) proteins.
      Appropriate RGS-Gbeta(5) complexes regulate both Galpha(o) and Galpha(q) proteins
      in vivo.

PMID- 11250152
TI  - Distinct functional properties of the TAP subunits coordinate the nucleotide
      dependent transport cycle.
AB  - BACKGROUND: The transporter associated with antigen processing (TAP) consists of
      two polypeptides, TAP1 and TAP2. TAP delivers peptides into the ER and forms a
      "loading complex" with MHC class I molecules and accessory proteins. Our previous
      experiments indicated that nucleotide binding to TAP plays a critical role in the
      uptake of peptide and the release of assembled class I molecules. To investigate
      whether the conserved nucleotide binding domains (NBDs) of TAP1 and TAP2 are
      functionally equivalent, we created TAP variants in which only one of the two ATP
      binding sites was mutated. RESULTS: Mutations in the NBDs had no apparent effect
      on the formation of the loading complex. However, both NBDs had to be functional
      for peptide uptake and transport. TAP1 binds ATP much more efficiently than does
      TAP2, while the binding of ADP by the two chains is essentially equivalent.
      Peptide-mediated release of MHC class I molecules from TAP was blocked only when
      the NBD of TAP1 was disrupted. A different NBD mutation that does not affect
      nucleotide binding has strikingly different effects on peptide transport activity
      depending on whether it is present in TAP1 or TAP2. CONCLUSIONS: Our findings
      indicate that ATP binding to TAP1 is the initial step in energizing the transport
      process and support the view that ATP hydrolysis at one TAP chain induces ATP
      binding at the other chain; this leads to an alternating and interdependent
      catalysis of both NBDs. Furthermore, our data suggest that the peptide-mediated
      undocking of MHC class I is linked to the transport cycle of TAP by
      conformational signals arising predominantly from TAP1.

PMID- 11250153
TI  - Dosage compensation in birds.
AB  - The Z and W sex chromosomes of birds have evolved independently from the
      mammalian X and Y chromosomes [1]. Unlike mammals, female birds are heterogametic
      (ZW), while males are homogametic (ZZ). Therefore male birds, like female
      mammals, carry a double dose of sex-linked genes relative to the other sex. Other
      animals with nonhomologous sex chromosomes possess "dosage compensation" systems
      to equalize the expression of sex-linked genes. Dosage compensation occurs in
      animals as diverse as mammals, insects, and nematodes, although the mechanisms
      involved differ profoundly [2]. In birds, however, it is widely accepted that
      dosage compensation does not occur [3-5], and the differential expression of Z
      linked genes has been suggested to underlie the avian sex-determination mechanism
      [6]. Here we show equivalent expression of at least six of nine Z chromosome
      genes in male and female chick embryos by using real-time quantitative PCR [7].
      Only the Z-linked ScII gene, whose ortholog in Caenorhabditis elegans plays a
      crucial role in dosage compensation [8], escapes compensation by this assay. Our
      results imply that the majority of Z-linked genes in the chicken are dosage
      compensated.

PMID- 11250154
TI  - Interaction of the virulence protein VirF of Agrobacterium tumefaciens with plant
      homologs of the yeast Skp1 protein.
AB  - The infection of plants by Agrobacterium tumefaciens leads to the formation of
      crown gall tumors due to the transfer of a nucleoprotein complex into plant cells
      that is mediated by the virulence (vir) region-encoded transport system (reviewed
      in [1-5]). In addition, A. tumefaciens secretes the Vir proteins, VirE2 and VirF,
      directly into plant cells via the same VirB/VirD4 transport system [6], and both
      assist there in the transformation of normal cells into tumor cells. The function
      of the 22 kDa VirF protein is not clear. Deletion of the virF gene in A.
      tumefaciens leads to diminished virulence [7, 8] and can be complemented by the
      expression of the virF gene in the host plant. This finding indicates that VirF
      functions within the plant cell [8]. Here, we report that the VirF protein is the
      first prokaryotic protein with an F box by which it can interact with plant
      homologs of the yeast Skp1 protein. The presence of the F box turned out to be
      essential for the biological function of VirF. F box proteins and Skp1p are both
      subunits of a class of E3 ubiquitin ligases referred to as SCF complexes. Thus,
      VirF may be involved in the targeted proteolysis of specific host proteins in
      early stages of the transformation process.

PMID- 11250155
TI  - PTEN regulates the ubiquitin-dependent degradation of the CDK inhibitor p27(KIP1)
      through the ubiquitin E3 ligase SCF(SKP2).
AB  - The PTEN tumor suppressor acts as a phosphatase for phosphatidylinositol-3,4,5
      trisphosphate (PIP3) [1, 2]. We have shown previously that PTEN negatively
      controls the G1/S cell cycle transition and regulates the levels of p27(KIP1), a
      CDK inhibitor [3, 4]. Recently, we and others have identified an ubiquitin E3
      ligase, the SCF(SKP2) complex, that mediates p27 ubiquitin-dependent proteolysis
      [5-7]. Here we report that PTEN and the PI 3-kinase pathway regulate p27 protein
      stability. PTEN-deficiency in mouse embryonic stem (ES) cells causes a decrease
      of p27 levels with concomitant increase of SKP2, a key component of the SCF(SKP2)
      complex. Conversely, in human glioblastoma cells, ectopic PTEN expression leads
      to p27 accumulation, which is accompanied by a reduction of SKP2. We found that
      ectopic expression of SKP2 alone is sufficient to reverse PTEN-induced p27
      accumulation, restore the kinase activity of cyclin E/CDK2, and partially
      overcome the PTEN-induced G1 cell cycle arrest. Consistently, recombinant
      SCF(SKP2) complex or SKP2 protein alone can rescue the defect in p27
      ubiquitination in extracts prepared from cells treated with a PI 3-kinase
      inhibitor. Our findings suggest that SKP2 functions as a critical component in
      the PTEN/PI 3-kinase pathway for the regulation of p27(KIP1) and cell
      proliferation.

PMID- 11250156
TI  - Intermolecular DNA interactions stimulated by the cohesin complex in vitro:
      implications for sister chromatid cohesion.
AB  - The establishment of sister chromatid cohesion during S phase and its dissolution
      at the metaphase-anaphase transition are essential for the faithful segregation
      of chromosomes in mitosis [1-4]. Recent studies in yeast genetics and Xenopus
      biochemistry have identified a large protein complex, cohesin, that plays a key
      role in sister chromatid cohesion [5-10]. The cohesin complex consists of a
      heterodimeric pair of SMC (structural maintenance of chromosomes) subunits and at
      least two non-SMC subunits. This structural organization is reminiscent of that
      of condensin, another major SMC protein complex that drives chromosome
      condensation in eukaryotic cells [11]. Condensin has been shown to reconfigure
      and compact DNA in vitro by utilizing the energy of ATP hydrolysis [12]. Very
      little is known, however, about how cohesin works at a mechanistic level. Here we
      report the first set of biochemical activities associated with an intact cohesin
      complex purified from HeLa cell extracts. The cohesin complex binds directly to
      double-stranded DNA and induces the formation of large protein-DNA aggregates. In
      the presence of topoisomerase II, cohesin stimulates intermolecular catenation of
      circular DNA molecules. This activity is in striking contrast to intramolecular
      knotting directed by condensin [13]. Cohesin also increases the probability of
      intermolecular ligation of linear DNA molecules in the presence of DNA ligase.
      Our results are consistent with a model in which cohesin functions as an
      intermolecular DNA crosslinker and is part of the molecular "glue" that holds
      sister chromatids together [14].

PMID- 11250157
TI  - Effects of a dominant interfering mutant of FADD on signal transduction in
      activated T cells.
AB  - The cytoplasmic adaptor protein FADD is an essential component of the death
      inducing signaling complexes (DISCs) that assemble when TNF receptor family
      members, such as Fas, are ligated. FADD inititates the proteolytic cascade that
      leads to apoptosis by binding to and promoting the autocatalytic activation of
      caspase-8 [1-4]. Surprisingly, FADD (but not caspase-8) is also required for T
      cells to proliferate upon their stimulation with mitogens [5-9]. Using transgenic
      mice expressing a dominant-negative mutant of FADD (FADD-DN), we show that
      functional FADD is required for T cells to proliferate in response to antigens in
      vivo as well as to mitogens in culture. The costimulation of wild-type and FADD
      DN T cells with mitogens revealed that FADD-DN T cells have a cell-autonomous
      defect in intracellular signaling. In contrast to another study [6], p53
      deficiency did not rescue mitogen-induced proliferation of FADD-DN T cells, and
      neither did enforced expression of the apoptosis inhibitor Bcl-2. Like wild-type
      T cells, FADD-DN T cells stimulated with mitogens mobilized intracellular calcium
      and activated members of the NF-kappaB transcription factor family as well as p38
      mitogen-activated protein kinase (MAPK) and p44/42 MAPK. Therefore, FADD must act
      downstream of or in parallel to these signaling pathways.

PMID- 11250158
TI  - Polycomb group genes control pattern formation in plant seed.
AB  - Transcriptional activators of the Trithorax group (TRX-G) and repressors of the
      Polycomb group (Pc-G) are involved in multiple aspects of embryogenesis in
      Drosophila and the mouse [1, 2] and appear to have a conserved role in the
      zygotic control of the development of the anterior-posterior axis [3, 4, 5]. In
      the model plant Arabidopsis, three Pc-G genes have been isolated and
      characterized to date. CURLY LEAF (CLF) represses the expression of a floral
      homeotic gene in vegetative tissues but does not appear to have a role in plant
      embryogenesis [6]. Two other Pc-G genes, FIS1/MEDEA [7, 8, 9], and FIS3/FIE [8,
      10] have been characterized in studies of mutants that produce seeds in the
      absence of fertilization. Seeds resulting from autonomous development in fis
      mutants do not contain an embryo but only endosperm, the second product of double
      fertilization in flowering plants [11, 12]. Thus, FIS genes are considered to be
      repressors of endosperm development before fertilization. We report that when fis
      ovules are fertilized, the endosperm patterning along the major polar axis is
      perturbed. Posterior structures develop in more anterior domains of the
      endosperm. This correlates with the ectopic expression of a posterior molecular
      marker. FIS genes appear to be potent regulators of the establishment of the
      anterior-posterior polar axis in the endosperm.

PMID- 11250159
TI  - TBP is not universally required for zygotic RNA polymerase II transcription in
      zebrafish.
AB  - General transcription factors TFIIA, B, D, E, F, H, and RNA polymerase II (Pol
      II) are required for accurate initiation of Pol II transcription. The TATA
      binding protein (TBP), a subunit of TFIID, is responsible for recognition of the
      TATA box, a core element shared by a category of class II promoters [1].
      Recently, novel TBP-like factors (TLFs) have been described in metazoan organisms
      [2]. In spite of the numerous in vitro studies describing the general role of TBP
      in RNA polymerase II (Pol lI) transcription initiation, the precise function of
      TBP and the newly described TLF is poorly understood in vivo. We inhibited TBP
      and TLF function in zebrafish embryos to study the role of these factors during
      zygotic transcription. A dominant-negative variant of TLF mRNA and a TBP
      morpholino antisense oligo was used to block either TLF or TBP function. Both TBP
      or TLF-blocked embryos developed normally until the midblastula stage; however,
      they then failed to gastrulate. Several zygotic regulatory genes were
      downregulated by a block in either TBP or TLF function, while others were
      differentially affected. These results suggest that TBP is not universally
      required for Pol II transcription in vertebrates and that there is a differential
      requirement for TBP and TLF during early embryogenesis.

PMID- 11250161
TI  - Raising the bar for gene patents.

PMID- 11250160
TI  - eat-11 encodes GPB-2, a Gbeta(5) ortholog that interacts with G(o)alpha and
      G(q)alpha to regulate C. elegans behavior.
AB  - In C. elegans, a G(o)/G(q) signaling network regulates locomotion and egg laying
      [1-8]. Genetic analysis shows that activated Ca(2+)/calmodulin-dependent protein
      kinase II (CaMKII) is suppressed by perturbations of this network, which include
      loss of the GOA-1 G(o)alpha, DGK-1 diacylglycerol kinase, EAT-16 G protein gamma
      subunit-like (GGL)-containing RGS protein, or an unidentified protein encoded by
      the gene eat-11 [9]. We cloned eat-11 and report that it encodes the Gbeta(5)
      ortholog GPB-2. Gbeta(5) binds specifically to GGL-containing RGS proteins, and
      the Gbeta(5)/RGS complex can promote the GTP-hydrolyzing activity of Galpha
      subunits [10, 11]. However, little is known about how this interaction affects G
      protein signaling in vivo. In addition to EAT-16, the GGL-containing RGS protein
      EGL-10 participates in G(o)/G(q) signaling; EGL-10 appears to act as an RGS for
      the GOA-1 G(o)alpha, while EAT-16 appears to act as an RGS for the EGL-30
      G(q)alpha [4, 5]. We have combined behavioral, electrophysiological, and
      pharmacological approaches to show that GPB-2 is a central member of the
      G(o)/G(q) network and that GPB-2 may interact with both the EGL-10 and EAT-16 RGS
      proteins to mediate the opposing activities of G(o)alpha and G(q)alpha. These
      interactions provide a mechanism for the modulation of behavior by antagonistic G
      protein networks.

PMID- 11250162
TI  - Quick guide: ATP synthase.

PMID- 11250163
TI  - The pyrin domain: a possible member of the death domain-fold family implicated in
      apoptosis and inflammation.

PMID- 11250165
TI  - Neuropsychology: music of the hemispheres.
AB  - Music may be the food of love but it is also good fodder for cognitive
      scientists. Here we highlight a recent study of a neuropsychological patient who
      has lost her ability to read music, but not text, in the absence of any other
      musical deficit.

PMID- 11250164
TI  - Replication checkpoint: preventing mitotic catastrophe.
AB  - A conserved network of signal transduction pathways prevents mitosis if DNA is
      damaged or its synthesis incomplete. Loss of this checkpoint control is
      detrimental to the developing embryo. Recent studies have shed new light on how
      the essential ATR and Chk1 protein kinases cooperate to prevent such a crisis.

PMID- 11250167
TI  - Cell polarity: squaring the circle.
AB  - Recent studies have found that Drosophila gene products required for zonula
      adherens formation in the ectoderm are also involved in the asymmetric cell
      division of the neuroblast. The results illustrate the reiterated use of groups
      of proteins to dictate cell polarity in epithelial and non-epithelial cells.

PMID- 11250168
TI  - Kinesin transport: driving kinesin in the neuron.
AB  - A plethora of cytoplasmic motors contribute to the directed transport of a wide
      range of cellular organelles and molecules. Recent studies have advanced our
      understanding of cargo attachment to motor molecules and the regulation of
      intracellular transport.

PMID- 11250169
TI  - Systems neuroscience: the slowly sleeping slab and slice.
AB  - The physiological functions of structured spontaneous activity in the brain, such
      as the slow oscillations characteristic of certain sleep states, remain unclear,
      but new studies using brain slices or slabs are starting to shed light on the
      underlying neural mechanisms.

PMID- 11250166
TI  - Chromosome movement: dynein-out at the kinetochore.
AB  - Cell biologists have long speculated that a minus end-directed motor localized at
      kinetochores contributes to the poleward movement of chromosomes during mitosis.
      Two recent studies provide direct evidence that cytoplasmic dynein can perform
      this function.

PMID- 11250170
TI  - Transcription elongation: the 'Foggy' is liftingellipsis.
AB  - Transcription can be controlled by regulating either the initiation or elongation
      of RNA chains. Recent studies highlight the importance of an elongation
      regulator, Spt5, in controlling gene expression in yeast, fruit fly and
      zebrafish; Spt5 may provide a link between transcriptional elongation and cell
      fate.

PMID- 11250171
TI  - Molecular motors: Kinesin's string variable.
AB  - A recent model suggests that the walking action of kinesin is due to a 13 residue
      'fundamental engine' called the neck linker domain, which cyclically zips and
      unzips to the main part of the heads. New experiments confirm one prediction of
      the model: that crosslinking the neck linker to the head should block motility.

PMID- 11250172
TI  - Development of atherosclerosis and plaque biology.
AB  - Atherosclerosis is a leading issue in mortality and morbidity in the civilized
      world. A number of hypotheses for atherogenesis indicate the complexity of
      initiation and development of this multifactorial disease. Morphologic types of
      lesions have long since been studied in order to understand plaque evolution and
      determinants of plaque complication, a frequent cause of acute ischemic
      accidents. Chemical and pathophysiological studies defined the wide spectrum of
      molecular interactions between cellular elements of atherosclerotic lesions.
      Recently, molecular biologic investigations provide a deeper insight into genetic
      predispositions for the disease and have widened our understanding of the
      pathogenic mechanisms. Until we can diminish the high prevalence of the disease,
      precise information is needed on the evolution of atherosclerosis in order to
      slow progression, select optimal therapies and prevent plaque complications and
      their consequences.

PMID- 11250173
TI  - Percutaneous transluminal angioplasty in patients with ischemic tissue necrosis
      is worthwhile.
AB  - PURPOSE: Ischemic tissue necrosis is usually associated with long or sequential
      arterial obstructions. As a result, the role of percutaneous transluminal
      angioplasty (PTA), which addresses only short lesions, in patients presenting
      with trophic changes remains questionable. The purpose of this study was to
      evaluate the effectiveness of PTA in diabetic and non-diabetic patients
      presenting with grade 4 Fontaine's classification. METHOD: Between January 1992
      and December 1997, 1352 patients with aorto-iliac and/or infrainguinal occlusive
      diseases were admitted to our institution. Three hundred and ten patients who
      presented with distal gangrene (95.5%) or ischemic ulcers (4.5%) were identified.
      The patients consisted of 117 diabetics and 193 non-diabetics. PTA alone was
      performed in 26 diabetics (group 1) and in 30 non-diabetics (group 2). Their
      charts were retrospectively reviewed and the patients were recalled for clinical
      examination and non-invasive monitoring. RESULTS: Follow-up was available for all
      patients and ranged from 1 to 4 years. The survival rate was significantly higher
      in diabetic patients than in non-diabetic patients (96% vs 77% at 1 year; p<0.05
      and 91% vs 66% at 3 years; p<0.05). In group 1, the primary cumulative patency
      rate at 1 and 3 years was 76%. In group 2, the primary cumulative patency rate at
      1 and 3 years were 85% and 80%, respectively. Three patients in group 1 required
      a redo PTA at 4 months, resulting in an assisted primary patency rate at 1 and 3
      years of 88%. In contrast, no patients in group 2 required additional PTA. In
      group 1, the limb salvage rate at 1 and 3 years was 84%; and in group 2, 80% and
      75%, respectively. CONCLUSION: The results of PTA in both groups were
      encouraging. Dilation of one or two short stenoses, despite multiple distal
      lesions, may improve distal flow sufficiently to promote wound healing. Thus,
      this procedure may be recommended in selected patients suffering from ischemic
      tissue loss. However, during the first 6 months following PTA, diabetic patients
      should be followed carefully with Duplex as they are prone to early restenosis.

PMID- 11250174
TI  - Hemodynamic results of femoral vein valve repair.
AB  - Our aim was to assess the hemodynamic and clinical responses associated with
      valve repair surgery in 37 patients with severe chronic venous insufficiency.
      Patients classified as C(4-6)E(P)A(SDP)P(R) (primary venous dysfunction with skin
      changes with reflux of superficial, deep and perforating veins) were submitted to
      a novel procedure combining the closed technique described by Kistner with the
      Dacron sleeve technique described by Hallberg (mean follow-up = 24 months). A
      significant improvement in Valsalva test results (P < 0.0001), ambulatory
      pressure (P = 0.0099), venous refilling time (P < 0.0001), and reflux index (P <
      0.0001) was observed. Postoperative reactive hyperemia and gradient tests
      confirmed absence of venous obstruction signs. On their last visit, 85.3% of the
      patients had no ulceration, and edema was absent or minimal in over 90%. About
      70% of the patients referred partial or complete relief of pain in the affected
      limb. The combined surgical technique was effective to control venous reflux 24
      months after the procedure. A longer follow-up would be necessary to assess long
      term results.

PMID- 11250175
TI  - Endovascular stenting of superficial femoral artery stenosis and occlusions:
      results and risk factor analysis.
AB  - PURPOSE: To determine the early and midterm results of femoro-popliteal
      angioplasty with adjunctive stenting and to identify factors affecting early and
      continuing success. METHODS: Sixty-nine consecutive balloon angioplasty
      procedures on the superficial femoral artery (SFA) were performed in 60 limbs and
      55 patients in the operating theater. Fifty-two percent of lesions were
      occlusions, and 87% involved the distal half or the whole segment of the SFA.
      Immediate endovascular stenting was used in all procedures, involving the
      placement of 105 stents, with a mean stented length of 13.8 cm. Twenty-nine
      procedures (43%) were performed for critical ischemia. Three-monthly duplex
      ultrasound was used for follow up assessment, with stenosis of > 50% defined as
      the endpoint for failure. The patient demographic and biochemical data, and
      procedural details were correlated with success criteria according to Society of
      Vascular Surgery standards. RESULTS: Initial technical success by intent to treat
      was 92%, with four procedure-related complications and no deaths. Initial success
      by anatomic, hemodynamic and clinical criteria were 98.3, 96.7 and 93.3%
      respectively (92.2, 90.6 and 87.5% by intent to treat). Cumulative primary
      patency at 6, 12, and 24 months was 73.1, 62.6 and 53.8%, and secondary patency
      84.9, 72.1 and 72.1% correspondingly. Significant factors relating to inferior
      patency were occlusions, stented segment length > 10 cm, procedure in
      claudicants, and the use of the Memotherm stent. CONCLUSIONS: Angioplasty and
      stenting of the superficial femoral artery has acceptable primary and secondary
      patency rates even in the presence of long stenosis and occlusions. A duplex
      surveillance program is recommended for early detection and timely treatment of
      restenosis.

PMID- 11250176
TI  - Surgical treatment for popliteal artery entrapment syndrome.
AB  - PURPOSE: This study was a retrospective review of 11 limbs of 10 patients with
      popliteal artery entrapment syndrome (PAES) treated surgically in a 20-yr period.
      METHODS: The patients were aged 34.7 +/- 17.4 SEM yr. Arteriographic findings
      varied, showing medial deviation in two limbs, poststenotic dilatation in four
      limbs and occlusion of the popliteal artery in five limbs. In addition, computed
      tomographic (CT) scanning showed positive findings of PAES in all the limbs.
      RESULTS: The surgical procedures consisted of musculotendonous section (MTS) with
      autogenous saphenous vein (ASV) graft in seven limbs, MTS and ASV patch
      angioplasty with or without thromboendarterectomy in three limbs, and MTS alone
      in one limb. All the ASV grafts were found to be patent during the postoperative
      follow-up period (10.9 +/- 4.0 yr). CONCLUSION: CT scanning was demonstrated to
      be the most sensitive diagnostic modality for PAES, and MTS with or without ASV
      grafting method was considered to be the best surgical procedure for PAES.

PMID- 11250177
TI  - Air travel related venous thromboembolism. Hawaii views.

PMID- 11250178
TI  - Air travel and deep vein thrombosis -- the London experience.

PMID- 11250179
TI  - Air travel-related deep venous thrombosis. Vienna views.

PMID- 11250180
TI  - Air travel-related deep venous thrombosis. Sydney views.

PMID- 11250181
TI  - Air travel-related deep venous thrombosis. Chicago views.

PMID- 11250182
TI  - Traveller's venous thromboembolism.

PMID- 11250183
TI  - Risk factors for venous thromboembolism following prolonged air travel: a
      prospective study.

PMID- 11250185
TI  - Could prolonged air travel be causally associated with subclavian vein
      thromboembolism?

PMID- 11250184
TI  - Deep vein thrombosis in airline passengers -- the incidence of deep vein
      thrombosis and the efficacy of elastic compression stockings.

PMID- 11250186
TI  - Colonisation of prosthetic grafts by immunocompetent cells in a sheep model.
AB  - The present study examined the distribution of immunocompetent cells in synthetic
      vascular grafts in an experimental sheep model. Sixty-two adult Merino sheep
      underwent synthetic patch closure of a longitudinal arteriotomy in the left
      common carotid artery. The synthetic patch materials used were gelatin sealed
      Dacron (n=10), fluoropassivated Dacron (n=10), Fluoropassiv (n=12), polyurethane
      (n=10), expanded polytetrafluoroethylene (n=10) and carbon-lined expanded
      polytetrafluoroethylene (n=10). The sheep were sacrificed after four weeks when
      the prosthetic patches were harvested and fixed in 10% neutral buffered formalin.
      Transverse sections were taken along the graft and paraffin embedded. Serial
      sections were stained with cell type specific antibodies to identify T
      lymphocytes (CD3(+)), dendritic cells (S-100(+)), endothelial cells (von
      Willebrand factor(+)) and smooth muscle cells (smooth muscle alpha-actin(+)). All
      six graft types contained CD3(+) and S-100(+) cells in the neointima, within the
      synthetic matrix and in the perigraft layer. Three different tissue responses to
      synthetic materials were observed and the grafts were classified accordingly into
      three groups: (1) gelatin sealed Dacron, fluoropassivated Dacron and
      Fluoropassiv; (2) expanded polytetrafluoroethylene and carbon-lined expanded
      polytetrafluoroethylene; (3) polyurethane. The three synthetic materials in Group
      1 showed almost identical reactions with least accumulation of immunocompetent
      cells within the synthetic material but greater accumulation of immuno
      inflammatory infiltrates in the perigraft vascular tissue. In this group, new
      vessels penetrated into the synthetic material and there was prominent formation
      of foreign body (giant) cells. Group 2 showed greater accumulation of
      immunocompetent cells within the synthetic material itself but only sparse immuno
      inflammatory infiltrates in the perigraft tissue. Group 3 showed a high degree of
      inflammatory response within both the synthetic material and the perigraft
      vascular tissue. These observations demonstrate that immunocompetent cells
      colonise the synthetic matrix of grafts and accumulate in the perigraft tissue,
      but inflammatory responses vary in different graft types.

PMID- 11250187
TI  - Tension-free left ITA graft -- the pericardial strip technique.
AB  - Emphysematous lung occupying the whole dome of the left pleural cavity and
      expanding well over the midline may occasionally present a significant problem
      for positioning of the left internal thoracic artery, although the graft has been
      mobilized up to its origin. To avoid an undue tension on it, we combined a well
      known technique of the pericardial incision with the pericardial strip technique,
      enabling the lung to expand freely.

PMID- 11250188
TI  - Coronary reoperations in patients with a patent internal mammary artery graft.
AB  - OBJECTIVE: Analysis of short and long term results, clinical, functional and
      subjective status of patients, with a patent arterial graft, after coronary
      reoperation (RECABG). METHODS: Perioperative and follow-up data of 71 patients,
      undergoing coronary reoperations (1987--8) were studied. A cross-sectional follow
      up was conducted, functional evaluation by the Duke Activity Status Index (DASI),
      and patient's evaluation of his life situation were registered. RESULTS:
      Perioperative mortality was 7%. Eleven patients died during follow-up. The 12
      month and 60-month survival was 96% and 80%. Event-free survival was 86% and 51%.
      Family doctors declared that 55/66 (83%) had benefitted from the coronary
      reoperations. New York Heart Association decreased significantly from 3.4 +/- 0.5
      preoperative versus 1.5 +/- 0.4 postoperative. The mean DASI was 38.06 +/- 10.42.
      At the moment of the cross-sectional follow-up, 45/55 patients (82%) declared to
      have benefitted from the coronary reoperations. CONCLUSION: Improvement in New
      York Heart Association-class, good postoperative functional capacity, and
      patients positive evaluation, justify coronary reoperations in patients with a
      patent internal mammary artery graft.

PMID- 11250189
TI  - Autotransfusion decreases blood usage following cardiac surgery -- a prospective
      randomized trial.
AB  - INTRODUCTION: 10% of blood issued by the National Blood Service (220,000) is
      utilised in cardiac procedures. Transfusion reactions, infection risk and cost
      should stimulate us to decrease this transfusion rate. We tested the efficacy of
      autotransfusion of washed postoperative mediastinal fluid in a prospective
      randomized trial. PATIENTS AND METHODS: 166 patients undergoing coronary artery
      bypass grafting (CABG), valve or CABG + valve procedures were randomized into
      three groups. The indication for transfusion was a postoperative haemoglobin (Hb)
      < 10 g/l or a packed cell volume (PCV) < 30. When applicable, group A patients
      received washed post-operative drainage fluid. Group B all received blood
      processed from the cardiopulmonary bypass (CPB) circuit following separation from
      CPB and if appropriate washed post-operative drainage fluid. Group C were
      controls. Groups were compared using analysis of variance. RESULTS: There was no
      significant difference in age, sex, type of operation, CPB time and preoperative
      Hb and PCV between the groups. Blood requirements were as shown. [table - see
      text] Twelve patients in group A and 10 in group B did not require a homologous
      transfusion following processing of the mediastinal drainage fluid. CONCLUSION:
      Autotransfusion of washed postoperative mediastinal fluid can decrease the amount
      of homologous blood transfused following cardiac surgery. There was no
      demonstrable benefit in processing blood from the CPB circuit as well as
      mediastinal drainage fluid.

PMID- 11250190
TI  - Does warm antegrade intermittent blood cardioplegia really protect the heart
      during coronary surgery?
AB  - OBJECTIVE: Intermittent antegrade blood cardioplegia (IABC) has been standardized
      as a routine technique for myocardial protection in coronary surgery. However, if
      the myocardium is known to tolerate short periods of ischemia during hypothermic
      arrest, it may be less tolerant of warm ischemia, so the optimal cardioplegic
      temperature of intermittent antegrade blood cardioplegia is still controversial.
      The aim of this study was to compare the effects of warm intermittent antegrade
      blood cardioplegia and cold intermittent antegrade blood cardioplegia on
      myocardial pH and different parameters of the myocardial metabolism. METHODS:
      Thirty patients undergoing first-time isolated coronary surgery were randomly
      allocated into two groups: group 1 (15 patients) received warm (37 degrees C)
      intermittent antegrade blood cardioplegia and group 2 (15 patients) received cold
      (4 degrees C) intermittent antegrade blood cardioplegia. The two randomization
      groups had similar demographic and angiographic characteristics. Total duration
      of cardiopulmonary bypass (108+/-17 and 98+/-21 min) and of aortic cross-clamping
      (70+/-13 and 65+/-15 min) were similar. The cardioplegic solutions were prepared
      by mixing blood with potassium and infused at a flow rate of 250 ml/min for a
      concentration of 20 mEq/l during 2 min after each anastomosis or after 15 min of
      ischemia. Intramyocardial pH was continuously measured during cardioplegic arrest
      by a miniature glass electrode and values were corrected by temperature.
      Myocardial metabolism was assessed before aortic clamping (pre-XCL), 1 min after
      removal of the clamp (XCL off) and 15 min after reperfusion (Rep) by collecting
      coronary sinus blood samples. All samples were analyzed for lactate, creatine
      kinase (MB fraction), myoglobin and troponin I. Creatine kinase and troponin I
      were also daily evaluated in peripheral blood during 6 days post-operatively.
      RESULTS: The clinical outcomes and the haemodynamic parameters between the two
      groups were identical. In group 1, XCL off and Rep were associated with higher
      coronary sinus release of lactate (5.5 +/- 1.8 and 2.2 +/- 0.5 mmol/l) than in
      group 2 (2.0 +/- 0.7 and 1.6 +/- 0.3 mmol/l, P < 0.05). Mean intramyocardial pH
      was lower in group 1 (7.23 +/- 0.08) than in group 2 (7.65 +/- 0.30, P < 0.05).
      There were no significant differences between the two groups with respect of
      creatine kinase (MB fraction) either after Rep or during the post-operative
      period. Lower coronary sinus release of myoglobin was detected at Rep in group 1
      (170 +/- 53 microg/l) than in group 2 (240 +/- 95 microg/l, P < 0.05). At day 1,
      a lower release of troponin I was found in group 1 (0.11 +/- 0.07 g/ml) compared
      to group 2 (0.17 +/- 0.07 ng/ml, P < 0.05). CONCLUSION: With regards to similar
      clinical and haemodynamic results, myocardial protection induced by warm IAEX is
      associated with more acidic conditions (intramyocardial pH and lactate release)
      and less myocardial injury (myoglobin and troponin I release) than cold
      intermittent antegrade blood cardioplegia during coronary surgery.

PMID- 11250191
TI  - Immunohistochemical and ultrastructural evidence that dendritic cells infiltrate
      stenotic aortocoronary saphenous vein bypass grafts.
AB  - We earlier speculated that antigen-presenting dendritic cells may be involved in
      the immune reactions leading to saphenous vein bypass graft failure. The purpose
      of this study was to confirm whether dendritic cells are present in stenotic
      human saphenous vein bypass grafts. Segments of stenotic saphenous vein grafts
      were explanted from 14 patients at re-do bypass operation and ten normal
      saphenous veins were harvested during femoro-popliteal grafting. Sections of
      specimens were analysed using cell type specific antibodies to identify dendritic
      cells (CD1a, S-100), T-lymphocytes (CD3), macrophages (CD68), smooth muscle cells
      (alpha-SMA) and endothelial cells (FVIII). Dual immunostaining, confocal
      immunofluorescent laser scanning microscopy and electron microscopy were used.
      Stenotic grafts showed structural alterations of intimal hyperplasia and varying
      degrees of atherosclerotic degeneration. No cells expressing CD1a and S-100 were
      observed in the intima and media of normal saphenous veins. Cells expressing
      these antigens were present around areas of medial neovascularization and within
      intimal atherosclerotic lesions in saphenous vein bypass grafts. Electron
      microscopy demonstrated the presence of cells containing a well-developed
      tubulovesicular system which is unique to cells from the dendritic cell family.
      Double immunohistochemistry and confocal immunofluorescent microscopy revealed
      the co-localization of T-lymphocytes with dendritic cells. Dendritic cells are
      present in stenotic saphenous vein bypass grafts. Dendritic cells may be
      responsible for antigen presentation and modulation of immune reactions in
      accelerated graft atherosclerosis through their interaction with T-lymphocytes.

PMID- 11250192
TI  - A case of coronary artery fistula draining into the pericardium causing hematoma.
AB  - A 28-yr old female patient admitted to our clinic because of dyspnea and chest
      pain. Her transesophageal echocardiography demonstrated a huge mass on the
      anterolateral wall of the left ventricle causing dysfunction of the myocardium.
      Coronary angiography demonstrated left anterior descending artery fistula
      draining into the pericardial cystic mass. Hydatic cyst was suspected and ELISA
      and hemagglutinin tests were both negative for Echinococcus granulosus. Magnetic
      resonance image of the heart showed a mass thought to be a hematoma inside the
      cyst. She underwent surgery. The cystic lesion with a pure hematoma inside, was
      excised, and the fistula between left anterior descending artery and the mass was
      ligated without any complications. To our knowledge, this is the first case of a
      pericardial hematoma due to a coronary artery fistula, in the English literature.

PMID- 11250193
TI  - The hydrophobin EAS is largely unstructured in solution and functions by forming
      amyloid-like structures.
AB  - BACKGROUND: Fungal hydrophobin proteins have the remarkable ability to self
      assemble into polymeric, amphipathic monolayers on the surface of aerial
      structures such as spores and fruiting bodies. These monolayers are extremely
      resistant to degradation and as such offer the possibility of a range of
      biotechnological applications involving the reversal of surface polarity. The
      molecular details underlying the formation of these monolayers, however, have
      been elusive. We have studied EAS, the hydrophobin from the ascomycete Neurospora
      crassa, in an effort to understand the structural aspects of hydrophobin
      polymerization. RESULTS: We have purified both wild-type and uniformly 15N
      labeled EAS from N. crassa conidia, and used a range of physical methods
      including multidimensional NMR spectroscopy to provide the first high resolution
      structural information on a member of the hydrophobin family. We have found that
      EAS is monomeric but mostly unstructured in solution, except for a small region
      of antiparallel beta sheet that is probably stabilized by four intramolecular
      disulfide bonds. Polymerised EAS appears to contain substantially higher amounts
      of beta sheet structure, and shares many properties with amyloid fibers,
      including a characteristic gold-green birefringence under polarized light in the
      presence of the dye Congo Red. CONCLUSIONS: EAS joins an increasing number of
      proteins that undergo a disorder-->order transition in carrying out their normal
      function. This report is one of the few examples where an amyloid-like state
      represents the wild-type functional form. Thus the mechanism of amyloid
      formation, now thought to be a general property of polypeptide chains, has
      actually been applied in nature to form these remarkable structures.

PMID- 11250194
TI  - Model for the motor component of dynein heavy chain based on homology to the AAA
      family of oligomeric ATPases.
AB  - BACKGROUND: Recent iterative methods for sequence alignment have indicated that
      the 380 kDa motor unit of dynein belongs to the AAA class of chaperone-like
      ATPases. These alignments indicate that the core of the 380 kDa motor unit
      contains a concatenated chain of six AAA modules, of which four correspond to the
      ATP binding sites with P-loop signatures described previously, and two are
      modules in which the P loop has been lost in evolution. RESULTS: We report
      predicted structures for the six AAA modules in the beta heavy chain of axonemal
      dynein, based upon their homology to a template of structurally conserved regions
      derived from three AAA proteins with experimentally determined structures
      (pdb:1A5T, pdb:1DOO, and pdb:1NSF). The secondary structural elements of the AAA
      modules in dynein correspond to regions of sequence that are relatively well
      conserved in different dynein isoforms. The tertiary structure of each AAA module
      comprises a major alpha/beta N domain from which a smaller all-alpha C domain
      protrudes at an angle, as part of the putative nucleotide binding cavity. The
      structures of the six modules are assembled into a ring, approximately 125 A in
      diameter, that resembles the structure of the dynein motor unit observed by
      electron microscopy. CONCLUSION: The predicted structures are supported by
      procedures that assess global, regional, and local quality, with the module
      containing the hydrolytic ATP binding site being supported the most strongly. The
      structural resemblance of the dynein motor to the hexameric assembly of AAA
      modules in the hsp100 family of chaperones suggests that the basic mechanism
      underlying the ATP-dependent translocation of dynein along a microtubule may have
      aspects in common with the ATP-dependent translocation of polypeptides into the
      interior compartment of chaperones.

PMID- 11250195
TI  - Computational modeling predicts the structure and dynamics of chromatin fiber.
AB  - BACKGROUND: The compact form of the chromatin fiber is a critical regulator of
      fundamental processes such as transcription and replication. These reactions can
      occur only when the fiber is unraveled and the DNA strands contained within are
      exposed to interact with nuclear proteins. While progress on identifying the
      biochemical mechanisms that control localized folding and hence govern access to
      genetic information continues, the internal structure of the chromatin fiber, let
      alone the structural pathways for folding and unfolding, remain unknown. RESULTS:
      To offer structural insights into how this nucleoprotein complex might be
      organized, we present a macroscopic computer model describing the mechanics of
      the chromatin fiber on the polymer level. We treat the core particles as
      electrostatically charged disks linked via charged elastic DNA segments and
      surrounded by a microionic hydrodynamic solution. Each nucleosome unit is
      represented by several hundred charges optimized so that the effective Debye
      Huckel electrostatic field matches the field predicted by the nonlinear Poisson
      Boltzmann equation. On the basis of Brownian dynamics simulations, we show that
      oligonucleosomes condense and unfold in a salt-dependent manner analogous to the
      chromatin fiber. CONCLUSIONS: Our predicted chromatin model shows good agreement
      with experimental diffusion coefficients and small-angle X-ray scattering data. A
      fiber of width 30 nm, organized in a compact helical zigzag pattern with about 4
      nucleosomes per 10 nm, naturally emerges from a repeating nucleosome folding
      motif. This fiber has a cross-sectional radius of gyration of R(c) = 8.66 nm, in
      close agreement with corresponding values for rat thymus and chicken erythrocyte
      chromatin (8.82 and 8.5 nm, respectively).

PMID- 11250196
TI  - Crystal structure of the calcium-loaded spherulin 3a dimer sheds light on the
      evolution of the eye lens betagamma-crystallin domain fold.
AB  - BACKGROUND: The betagamma-crystallins belong to a superfamily of two-domain
      proteins found in vertebrate eye lenses, with distant relatives occurring in
      microorganisms. It has been considered that an eukaryotic stress protein,
      spherulin 3a, from the slime mold Physarum polycephalum shares a common one
      domain ancestor with crystallins, similar to the one-domain 3-D structure
      determined by NMR. RESULTS: The X-ray structure of spherulin 3a shows it to be a
      tight homodimer, which is consistent with ultracentrifugation studies. The (two
      motif) domain fold contains a pair of calcium binding sites very similar to those
      found in a two-domain prokaryotic betagamma-crystallin fold family member,
      Protein S. Domain pairing in the spherulin 3a dimer is two-fold symmetric, but
      quite different in character from the pseudo-two-fold pairing of domains in
      betagamma-crystallins. There is no evidence that the spherulin 3a single domain
      can fold independently of its partner domain, a feature that may be related to
      the absence of a tyrosine corner. CONCLUSION: Although it is accepted that the
      vertebrate two-domain betagamma-crystallins evolved from a common one-domain
      ancestor, the mycetezoan single-domain spherulin 3a, with its unique mode of
      domain pairing, is likely to be an evolutionary offshoot, perhaps from as far
      back as the one-motif ancestral stage. The spherulin 3a protomer stability
      appears to be dependent on domain pairing. Spherulin-like domain sequences that
      are found within bacterial proteins associated with virulence are likely to bind
      calcium.

PMID- 11250197
TI  - Crystal structure of the 100 kDa arsenite oxidase from Alcaligenes faecalis in
      two crystal forms at 1.64 A and 2.03 A.
AB  - BACKGROUND: Arsenite oxidase from Alcaligenes faecalis NCIB 8687 is a
      molybdenum/iron protein involved in the detoxification of arsenic. It is induced
      by the presence of AsO(2-) (arsenite) and functions to oxidize As(III)O(2-),
      which binds to essential sulfhydryl groups of proteins and dithiols, to the
      relatively less toxic As(V)O(4)(3-) (arsenate) prior to methylation. RESULTS:
      Using a combination of multiple isomorphous replacement with anomalous scattering
      (MIRAS) and multiple-wavelength anomalous dispersion (MAD) methods, the crystal
      structure of arsenite oxidase was determined to 2.03 A in a P2(1) crystal form
      with two molecules in the asymmetric unit and to 1.64 A in a P1 crystal form with
      four molecules in the asymmetric unit. Arsenite oxidase consists of a large
      subunit of 825 residues and a small subunit of approximately 134 residues. The
      large subunit contains a Mo site, consisting of a Mo atom bound to two pterin
      cofactors, and a [3Fe-4S] cluster. The small subunit contains a Rieske-type [2Fe
      2S] site. CONCLUSIONS: The large subunit of arsenite oxidase is similar to other
      members of the dimethylsulfoxide (DMSO) reductase family of molybdenum enzymes,
      particularly the dissimilatory periplasmic nitrate reductase from Desulfovibrio
      desulfuricans, but is unique in having no covalent bond between the polypeptide
      and the Mo atom. The small subunit has no counterpart among known Mo protein
      structures but is homologous to the Rieske [2Fe-2S] protein domain of the
      cytochrome bc(1) and cytochrome b(6)f complexes and to the Rieske domain of
      naphthalene 1,2-dioxygenase.

PMID- 11250198
TI  - Restriction enzyme BsoBI-DNA complex: a tunnel for recognition of degenerate DNA
      sequences and potential histidine catalysis.
AB  - BACKGROUND: Restriction endonucleases form a diverse family of proteins with
      substantial variation in sequence, structure, and interaction with recognition
      site DNA. BsoBI is a thermophilic restriction endonuclease that exhibits both
      base-specific and degenerate recognition within the sequence CPyCGPuG. RESULTS:
      The structure of BsoBI complexed to cognate DNA has been determined to 1.7 A
      resolution, revealing several unprecedented features. Each BsoBI monomer is
      formed by inserting a helical domain into an expanded EcoRI-type catalytic
      domain. DNA is completely encircled by a BsoBI dimer. Recognition sequence DNA
      lies within a 20 A long tunnel of protein that excludes bulk solvent.
      Interactions with the specific bases are made in both grooves through direct and
      water-mediated hydrogen bonding. Interaction with the degenerate position is
      mediated by a purine-specific hydrogen bond to N7, ensuring specificity, and
      water-mediated H bonding to the purine N6/O6 and pyrimidine N4/O4, allowing
      degeneracy. In addition to the conserved active site residues of the DX(n)(E/D)ZK
      restriction enzyme motif, His253 is positioned to act as a general base.
      CONCLUSIONS: A catalytic mechanism employing His253 and two metal ions is
      proposed. If confirmed, this would be the first example of histidine-mediated
      catalysis in a restriction endonuclease. The structure also provides two novel
      examples of the role of water in protein-DNA interaction. Degenerate recognition
      may be mediated by employing water as a hydrogen bond donor or acceptor. The
      structure of DNA in the tunnel may also be influenced by the absence of bulk
      solvent.

PMID- 11250199
TI  - Structural insights into the mode of action of a pure antiestrogen.
AB  - BACKGROUND: Estrogens exert their effects on target tissues by binding to a
      nuclear transcription factor termed the estrogen receptor (ER). Previous
      structural studies have demonstrated that each class of ER ligand (agonist,
      partial agonist, and SERM antagonist) induces distinctive orientations in the
      receptor's carboxy-terminal transactivation helix. The conformation of this
      portion of the receptor determines whether ER can recruit and interact with the
      components of the transcriptional machinery, thereby facilitating target gene
      expression. RESULTS: We have determined the structure of rat ERbeta ligand
      binding domain (LBD) in complex with the pure antiestrogen ICI 164,384 at 2.3 A
      resolution. The binding of this compound to the receptor completely abolishes the
      association between the transactivation helix (H12) and the rest of the LBD. The
      structure reveals that the terminal portion of ICI's bulky side chain substituent
      protrudes from the hormone binding pocket, binds along the coactivator
      recruitment site, and physically prevents H12 from adopting either its
      characteristic agonist or AF2 antagonist orientation. CONCLUSIONS: The binding
      mode adopted by the pure antiestrogen is similar to that seen for other ER
      antagonists. However, the size and resultant positioning of the ligand's side
      chain substituent produces a receptor conformation that is distinct from that
      adopted in the presence of other classes of ER ligands. The novel observation
      that binding of ICI results in the complete destabilization of H12 provides some
      indications as to a possible mechanism for pure receptor antagonism.

PMID- 11250200
TI  - The structure and activity of a monomeric interferon-gamma:alpha-chain receptor
      signaling complex.
AB  - BACKGROUND: Interferon-gamma (IFN-gamma) is a homodimeric cytokine that exerts
      its various activities by inducing the aggregation of two different receptors.
      The alpha chain receptor (IFN-gammaRalpha) is a high affinity receptor that binds
      to IFN-gamma in a symmetric bivalent manner to form a stable, intermediate 1:2
      complex. This intermediate forms a binding template for the subsequent binding of
      two copies of the second receptor, beta chain receptor (IFN-gammaRbeta),
      producing the active 1:2:2 signaling complex. RESULTS: A single chain monovalent
      variant of IFN-gamma (scIFN-gamma) was constructed and complexed to one copy of
      the extracellular domain (ECD) of IFN-gammaRalpha. The structure of this 1:1
      complex was determined and the hormone-receptor interface shown to be
      characterized by a number of hydrophilic interactions mediated by several highly
      ordered water networks. The scIFN-gamma interface consists of segments from each
      of the monomer chains of the homodimer. The principal hydrophobic contact of the
      receptor involves a tripeptide segment of the receptor having an unusual and high
      energy conformation. Despite containing only one binding site for IFN
      gammaRalpha, the monovalent scIFN-gamma molecule has significant activity in
      antiviral biological assays. CONCLUSIONS: ScIFN-gamma binds the ECD of IFN
      gammaRalpha through a highly hydrated interface with an important set of hormone
      receptor contacts mediated through structured waters. Although the interface is
      highly hydrated, it supports tight binding and has a considerable degree of
      specificity. The biological activity of scIFN-gamma confirms that the scIFN
      gamma:IFN-gammaRalpha complex represents a productive intermediate and that it
      can effectively recruit the other required component, IFN-gammaRbeta, to signal
      based on the 1:1:1 complex.

PMID- 11250201
TI  - The crystal structure of an asymmetric complex of the two nucleotide binding
      components of proton-translocating transhydrogenase.
AB  - BACKGROUND: Membrane-bound ion translocators have important functions in biology,
      but their mechanisms of action are often poorly understood. Transhydrogenase,
      found in animal mitochondria and bacteria, links the redox reaction between
      NAD(H) and NADP(H) to proton translocation across a membrane. Linkage is achieved
      through changes in protein conformation at the nucleotide binding sites. The
      redox reaction takes place between two protein components located on the membrane
      surface: dI, which binds NAD(H), and dIII, which binds NADP(H). A third
      component, dII, provides a proton channel through the membrane. Intact membrane
      located transhydrogenase is probably a dimer (two copies each of dI, dII, and
      dIII). RESULTS: We have solved the high-resolution crystal structure of a dI:dIII
      complex of transhydrogenase from Rhodospirillum rubrum-the first from a
      transhydrogenase of any species. It is a heterotrimer, having two polypeptides of
      dI and one of dIII. The dI polypeptides fold into a dimer. The loop on dIII,
      which binds the nicotinamide ring of NADP(H), is inserted into the NAD(H) binding
      cleft of one of the dI polypeptides. The cleft of the other dI is not occupied by
      a corresponding dIII component. CONCLUSIONS: The redox step in the
      transhydrogenase reaction is readily visualized; the NC4 atoms of the
      nicotinamide rings of the bound nucleotides are brought together to facilitate
      direct hydride transfer with A-B stereochemistry. The asymmetry of the dI:dIII
      complex suggests that in the intact enzyme there is an alternation of
      conformation at the catalytic sites associated with changes in nucleotide binding
      during proton translocation.

PMID- 11250204
TI  - Entering a new phase: using solvent halide ions in protein structure
      determination.

PMID- 11250205
TI  - Familial and sporadic primary pulmonary hypertension is caused by BMPR2 gene
      mutations resulting in haploinsufficiency of the bone morphogenetic protein tuype
      II receptor.

PMID- 11250206
TI  - Immunolocalisation of BMPR-II and TGF-beta type I and II receptors in primary
      plexogenic pulmonary hypertension.

PMID- 11250202
TI  - Crystal structures of the HslVU peptidase-ATPase complex reveal an ATP-dependent
      proteolysis mechanism.
AB  - BACKGROUND: The bacterial heat shock locus HslU ATPase and HslV peptidase
      together form an ATP-dependent HslVU protease. Bacterial HslVU is a homolog of
      the eukaryotic 26S proteasome. Crystallographic studies of HslVU should provide
      an understanding of ATP-dependent protein unfolding, translocation, and
      proteolysis by this and other ATP-dependent proteases. RESULTS: We present a 3.0
      A resolution crystal structure of HslVU with an HslU hexamer bound at one end of
      an HslV dodecamer. The structure shows that the central pores of the ATPase and
      peptidase are next to each other and aligned. The central pore of HslU consists
      of a GYVG motif, which is conserved among protease-associated ATPases. The
      binding of one HslU hexamer to one end of an HslV dodecamer in the 3.0 A
      resolution structure opens both HslV central pores and induces asymmetric changes
      in HslV. CONCLUSIONS: Analysis of nucleotide binding induced conformational
      changes in the current and previous HslU structures suggests a protein unfolding
      coupled translocation mechanism. In this mechanism, unfolded polypeptides are
      threaded through the aligned pores of the ATPase and peptidase and translocated
      into the peptidase central chamber.

PMID- 11250207
TI  - One year analysis of an ongoing international randomized study of mycophenolate
      mofetil (MMF) vs azathioprine (AZA) in lung transplantation.

PMID- 11250208
TI  - A novel method based on computerized scoring of rejection for the prediction of
      coronary vascuolpathy validated by intravascular ultrasound.

PMID- 11250209
TI  - CTLA4Ig and donor-specific transfusion prolongs cardiac allograft survival in the
      miniature swine.

PMID- 11250210
TI  - Haptoglobin polymorphism influences the development of cardiac transplant
      vasculopathy.

PMID- 11250211
TI  - Prognostic value of a new intravascular ultrasound score in graft vessel disease.

PMID- 11250212
TI  - Usefulness of post-transplant wall motion analysis by tissue Doppler imaging in
      patients with cardiac allograft vasculopathy: evaluation of functional severity
      and timing of follow-up cardiac catheterizations.

PMID- 11250213
TI  - Are there specific risk factors for fatal allograft vasculopathy? An analysis of
      over 7,000 cardiac transplant patients.

PMID- 11250214
TI  - Coronary atherosclerosis in cardiac transplant patients treated with total
      lymphoid irradiation.

PMID- 11250215
TI  - In vivo donor adenoviral-mediated transtracheal transfection of human IL-10 (HIL
      10) gene ameliorates ischemia-reperfusion (IR) injury and enhances transplanted
      lung function.

PMID- 11250216
TI  - Recipient treatment with trimetazidine improves graft function and protects the
      energy status after lung transplantation.

PMID- 11250217
TI  - First results 24 hours after orthotopic heart transplantation from non-heart
      beating donors in pigs.

PMID- 11250218
TI  - Endothelial function after brain death.

PMID- 11250219
TI  - Biopsy diagnosis of disease recurrence after transplantation (TX) for pulmonary
      sarcoidosis: a multicentre study.

PMID- 11250220
TI  - Upregulation of BCL-2 via hyperbaric pressure transfection of TGF- beta1
      ameliorates ischemia/reperfusion injury in rat cardiac allografts.

PMID- 11250221
TI  - Improvement of cardiac allograft function by 1400W, a highly selective inducible
      nitric oxide synthase inhibitor and superoxide dismutase - role of peroxynitrite.

PMID- 11250222
TI  - Anti-thymocyte globulin treatment is associated with complement deposition in
      early cardiac transplant biopsies.

PMID- 11250223
TI  - Nonimmunologic rejection of the heart.

PMID- 11250224
TI  - Interstitial pneumonitis after lung or heart-lung transplantation in very young
      recipients.

PMID- 11250225
TI  - Early T lymphocyte trafficking after allo-transplantation.

PMID- 11250226
TI  - Vascular endothelial growth factor-D (VEGF-D) is an endothelial hyperpermeability
      inducing growth factor differentially expressed in human cardiac allografts.

PMID- 11250227
TI  - Sustained production of the chemokine MIG precedes intimal thickening in chronic
      rejection.

PMID- 11250228
TI  - Matrixmetalloproteinase (MMP) 9 activity and impaired coronary vasomotor function
      after cardiac transplantation in rats.

PMID- 11250229
TI  - IL-4 promotor gene polymorphism in heart transplantation.

PMID- 11250230
TI  - A novel scavenger of nitric oxide decreases heme protein nitrosylation and
      prolongs graft survivial during cardiac transplant rejection.

PMID- 11250231
TI  - Oxidative stress of cardiac transplantation is associated with decreased BCL-2
      expression and increased NFKB activity.

PMID- 11250232
TI  - Lung transplantation for cystic fibrosis; the effect of B cepacia genomovars on
      post transplant outcomes.

PMID- 11250233
TI  - Indirect allorecognition and alloantibody production precede obliterative airway
      disease development after tracheal transplantation in mice.

PMID- 11250234
TI  - Impairment of cytolytic activity in allograft environment affects early medial
      cell loss but does not alter outcome of allograft arteriosclerosis.

PMID- 11250235
TI  - Elevation of serum big endothelin is associated with endothelial dysfunction in
      patients with chronic heart failure.

PMID- 11250237
TI  - A dominant negative isoform of the serum-response factor (SRF) is increased in
      the failing human heart.

PMID- 11250236
TI  - Tumour necrosis factor- a A2 polymorphism; a predisposing factor to non-ischaemic
      myocardial dysfunction?

PMID- 11250238
TI  - The effects of mycophenolate mofetil on cardiac allograft survival and cardiac
      allograft vasculopathy in miniature swine.

PMID- 11250239
TI  - Co-administration of tacrolimus and mycophenolate mofetil does not increase
      mycophenolic acid (MPA) exposure, but co-administration of cyclosporine inhibits
      the enterohepatic recirculation of MPA, thereby decreasing its exposure.

PMID- 11250240
TI  - ISATX247: a novel calcineurin inhibitor.

PMID- 11250241
TI  - Eotaxin and prednisolone concentrations regulate the mobilisation of peripheral
      blood eosinophils preceding heart allograft rejection.

PMID- 11250242
TI  - Cyclosporine verus tacrolimus in heart transplantation: an ISHLT/UNOS registry
      analysis.

PMID- 11250243
TI  - Current practices: immunosuppression induction, maintenance and rejection
      regimens in 213 consecutive transplant recipients.

PMID- 11250244
TI  - Early experience with sirolimus in lung transplant recipients.

PMID- 11250245
TI  - Pharmacodynamic (PD) measurements of the immunosuppressive effects of the
      combination of cyclosporine (CY) and mycophenolate mofetil (MMF): correlation
      between drug dose and lymphocyte function.

PMID- 11250246
TI  - Benefit of mycophenolate-mofetil (MMF) in patients with cyclosporine (CYA)
      induced nephropathy after cardiac transplantation.

PMID- 11250247
TI  - Sirolimus(rapamycin) allows renal recovery in lung and heart transplant
      recipients with chronic renal impairment.

PMID- 11250248
TI  - Clinical value of brain natriuretic peptide for candidate selection before
      cardiac transplantation.

PMID- 11250249
TI  - Does hyperuricemia predict adverse clinical outcome while awaiting heart
      transplantation?

PMID- 11250250
TI  - Relationship between peak exercise oxygen consumption and QTC in patients with
      advanced heart failure.

PMID- 11250251
TI  - Does HDL-cholesterol level predict clinical outcome in advanced heart failure?

PMID- 11250252
TI  - Predicting a patient's waiting time to heart transplant in the UK.

PMID- 11250253
TI  - Indirect alloresponses are more pronounced in non-rejecting lung than heart
      allografts.

PMID- 11250254
TI  - Binding of anti-HLA class I antibodies to airway epithelial cells induces
      activation and growth factor production and indirectly upregulates lung
      fibroblast proliferation.

PMID- 11250255
TI  - Recipient cells form the proliferative lesion in the rat heterotopic tracheal
      allograft model of obliterative airway disease (OAD).

PMID- 11250256
TI  - Neutralization of tumor necrosis factor-alpha or interleukin-1 prevents
      obliterative airway disease in HLA-A2 transgenic murine tracheal allografts.

PMID- 11250257
TI  - Blockade of PDGF receptor protein-tyrosine kinase activity effectively inhibits
      development of rat CMV infection enhanced experimental obliterative
      bronchiolitis.

PMID- 11250258
TI  - Cell-mediated immunity to collagen V in lung transplant recipients: correlation
      with collagen V release into BAL fluid.

PMID- 11250259
TI  - The emergence of co-morbid diseases impacting survival after cardiac
      transplantation, a ten year multi-institutional experience.

PMID- 11250260
TI  - Short-term survival with combined heart-kidney or combined heart-liver
      transplantation with allografts from a single donor.

PMID- 11250261
TI  - Survival of diabetic patients following cardiac transplant.

PMID- 11250262
TI  - Who is most likely to enjoy long term survival after cardiac transplantation?
      Risk stratification in a 10 year multi-institutional experience.

PMID- 11250263
TI  - Community acquired respiratory viruses in lung transplant patients: incidence and
      outcomes.

PMID- 11250264
TI  - Functional relevance of sympathetic reinnervation for the transplanted heart.

PMID- 11250265
TI  - Heart transplantation in Friedreich's ataxia and other neuromuscular diseases.

PMID- 11250266
TI  - Treatment of respiratory syncytial viral and parainfluenza lower respiratory
      tract infection in lung transplant patients.

PMID- 11250267
TI  - Direct fluorescent antibody testing in the diagnosis of influenzae infection in
      lung transplant recipients.

PMID- 11250268
TI  - Incidence of bronchiolitis obliterans syndrome unaffected by absence of
      cytomegalovirus.

PMID- 11250270
TI  - Chlamydia pneumoniae is associated with graft dysfunction after lung
      transplantation.

PMID- 11250269
TI  - Bronchiolitis obliterans with organizing pneumonia: possible association with
      human herpes virus-7 infection after lung transplantation.

PMID- 11250271
TI  - Endothelial-cell selective CTL arise from limited precursor subsets of
      alloreactive CD8+ T cells and show reduced clonal expansion.

PMID- 11250272
TI  - Differential modulation of alloreactive T cell receptor expression induced by
      allogeneic bone marrow and splenocyte infusions.

PMID- 11250273
TI  - The role of indirect recognition of donor MHC class II peptides in cardiac
      transplantation in miniature swine.

PMID- 11250274
TI  - Mechanisms of tolerance induction in the heart/kidney model in miniature swine.

PMID- 11250275
TI  - Peripheral expansion of circulating TH1 cells predicts coronary endothelial
      dysfunction after cardiac transplantation.

PMID- 11250276
TI  - Neonatal infusion of allogeneic fetal liver cells induces non-specific acceptance
      of cardiac allografts without diminution of alloreactivity to skin grafts and in
      vitro assays.

PMID- 11250277
TI  - Heart-lung transplantation for Eisenmenger's syndrome: operative risks and late
      outcomes of 51 consecutive cases from a single institution.

PMID- 11250278
TI  - Intrathoracic organ transplantation for patients with primary pulmonary
      hypertension.

PMID- 11250279
TI  - Lung transplantation for lymphangioleiomyomatosis.

PMID- 11250280
TI  - Lung transplantation in patients with scleroderma.

PMID- 11250281
TI  - Interleukin-8 release during ischemia-reperfusion correlates with early graft
      function in human lung transplantation.

PMID- 11250282
TI  - Mutations in the TGF-beta type 1 receptor, ALK1, in combined primary pulmonary
      hypertension and hereditary haemorrhagic telangiectasia, implies pathway
      specificity.

PMID- 11250283
TI  - Accuracy of currently utilized clinical diagnostic strategy in primary pulmonary
      hypertension: validation against pathologic diagnosis.

PMID- 11250284
TI  - Influence of four different immunosuppressive protocols on acute and chronic
      rejection (BOS) after lung transplantation - experiences in 120 patients.

PMID- 11250285
TI  - Features of bronchoalveolar lavage (BAL) in lung transplant recipients (LTR) who
      later develop bronchiolitis obliterans syndrome (BOS).

PMID- 11250286
TI  - Effect of HLA-DR mismatch on lung transplant outcome.

PMID- 11250287
TI  - Interventional bronchoscopy for the management of airway complications following
      lung transplantation.

PMID- 11250288
TI  - Native lung volume reduction surgery following single lung transplantation (SLTX)
      for emphysema.

PMID- 11250289
TI  - Outcome of hepatitis C positive donors in cardiac transplant recipients in triple
      drug immunosuppression (TDI).

PMID- 11250290
TI  - Increased risk of CMV infection in heart transplant patients on mycophenolate
      mofetil.

PMID- 11250291
TI  - Long term results of hyperimmunoglobulin CMV-prophylaxis in 377 heart transplant
      recipients.

PMID- 11250292
TI  - Prevalence and outcome of hepatitis B virus (HBV) infection following thoracic
      organ transplantation.

PMID- 11250293
TI  - Cytomegalovirus infection prophylaxis following heart transplantation: comparison
      of two regimes.

PMID- 11250294
TI  - Syncope following orthotopic heart transplantation.

PMID- 11250295
TI  - Morbidity and mortality beyond the 10th year following heart transplant. Data
      from a population of 137 patients.

PMID- 11250296
TI  - Sudden death after heart transplantation: the major mode of death.

PMID- 11250297
TI  - Retransplantation of intrathoracic organs - is a cautious approach still
      justified?

PMID- 11250299
TI  - Cardioprotective effects of ATP-sensitive potassium channel opener (cromakalim)
      in surgically induced cardiac arrest.

PMID- 11250298
TI  - A multi-institutional study of cardiac retransplantation: incidence, risk factors
      for mortality, and outcome.

PMID- 11250300
TI  - The optimal pressure for initial flushout in heart procurement with the UW
      solution.

PMID- 11250302
TI  - Extending myocardial preservation with cyclosporine a treatment.

PMID- 11250301
TI  - Cardiac allografts with ischemic time over 300 minutes.

PMID- 11250303
TI  - Use of long-term preserved organs in heart transplantation : post-operative
      results and long term follow up.

PMID- 11250304
TI  - Prospective randomized clinical study of Celsior vs University of Wisconsin in
      double lung transplant.

PMID- 11250305
TI  - Controlled perfusion decreases lung transplant reperfusion injury in the setting
      of high flow reperfusion.

PMID- 11250306
TI  - Effect of controlled reperfusion techniques in human lung transplantation.

PMID- 11250307
TI  - Recipient intramuscular gene transfer of naked plasmid TGFbeta1 ameliorates lung
      graft reperfusion injury.

PMID- 11250308
TI  - Detection of IL-10 in the exhaled breath condensate, plasma and tissue during
      ischemia-reperfusion injury in experimental lung transplantation.

PMID- 11250309
TI  - Efficiency, efficacy and adverse effects of adenovirus versus liposome-mediated
      ex vivo immunosuppressive cytokine gene transfer on the functional cardiac
      allografts.

PMID- 11250310
TI  - Sustained rantes production is necessary for CAV development.

PMID- 11250311
TI  - The role of vitronectin receptor and tissue factor in the pathogenesis of
      transplant coronary vasculopathy.

PMID- 11250312
TI  - Impact of type 1 diabetes on microvascular vs. macrovascular involvement with
      TXCAD: is there a difference in models of the disease?

PMID- 11250313
TI  - TC99M MCP-1 imaging of chronic rejection in rat cardiac allografts.

PMID- 11250314
TI  - Do vascular compartments differ in the development of chronic rejection?

PMID- 11250315
TI  - Increased death inducing receptors in vivo and activation-induced T-cell death by
      anti-thymocyte antibody treatment of stable cardiac transplant recipients.

PMID- 11250316
TI  - Immunohistochemical localization of oxidized low-density lipoprotein (OXLDL) and
      macrophages in coronary arteries: human heart allografts versus human native
      hearts.

PMID- 11250317
TI  - Heterotopic abdominal heart transplantation: the answer to the donor shortage?

PMID- 11250318
TI  - A novel contractile artificial myocardial tissue - on the way to the
      bioartificial heart.

PMID- 11250319
TI  - Surgical treatment of post infarct left ventricular aneurysm tachyarrhythmias
      with cryoablation and endoaneurysmoraphy.

PMID- 11250320
TI  - In vivo monitoring of myoblast transplantation into rat myocardium.

PMID- 11250321
TI  - Chronic therapy with the acorn cardiac support device in dogs with chronic heart
      failure: three and six months hemodynamic, histologic and ultrastructural
      findings.

PMID- 11250322
TI  - Long-term outcomes of dynamic cardiomyoplasty: what we learned and challenges for
      future applications.

PMID- 11250323
TI  - Left ventricular assist device support for medically unresponsive pulmonary
      hypertension from left ventricular failure.

PMID- 11250324
TI  - Aortic valve stenosis induced by left ventricular assist device (LVAD).

PMID- 11250325
TI  - Comparison of postoperative course of S100 protein and neuron-specific enolase in
      patients after implantation of axial and pulsatile flow LVADS.

PMID- 11250326
TI  - Ten year experience of FK 506 for adult cardiac transplantation at a single
      institution.

PMID- 11250327
TI  - Tacrolimus versus cyclosporine after HTX: comparison of long-term effects.

PMID- 11250328
TI  - Tacrolimus/mycophenolate mofetil vs cyclosporine/mycophenolate mofetil:
      comparison of mycophenolate acid trough levels and coronary vasomotor function.

PMID- 11250330
TI  - Therapeutic drug monitoring (TDM) of prednisolone in lung transplantation.

PMID- 11250329
TI  - The differential metabolic impact of tacrolimus and cyclosporine
      immunosuppression in black heart transplant recipients: hyperlipidemia,
      hypertension and hyperglycemia.

PMID- 11250331
TI  - Improvement of chronic renal failure after introduction of mycophenolate mofetil
      and reduction of cyclosporine dose.

PMID- 11250332
TI  - Introduction of mycophenolate mofetil and cyclosporine withdrawal in heart
      transplant patients with chronic renal insufficiency.

PMID- 11250333
TI  - Risk factors and outcome in patients with hemodynamically unstable rejection
      after heart transplantation.

PMID- 11250335
TI  - Effect of Daclizumab induction therapy on the development of cardiac transplant
      vasculopathy.

PMID- 11250334
TI  - Detection and prediction of acute heart transplant rejection with the myocardial
      T2 determination provided by a black-blood magnetic resonance imaging sequence.

PMID- 11250336
TI  - Plasma exchange before and after cardiac transplantation.

PMID- 11250337
TI  - Long term follow-up of sensitized patients.

PMID- 11250338
TI  - Evaluation of pre-transplant sensitization: a survey of tissue typing
      laboratories.

PMID- 11250339
TI  - Time course and determinants of graft vascular remodelling in heart transplant
      recipients: a prospective study.

PMID- 11250340
TI  - Cardiac allograft vasculopathy in heart transplant recipients: a
      bacteriosclerosis by chlamydia pneumoniae?

PMID- 11250341
TI  - Homocysteine/coronary atherosclerosis and cardiac transplantation:a case control
      study.

PMID- 11250342
TI  - Low incidence of graft arteriosclerosis after cardiac transplantation - risk
      factor analysis for patients with induction therapy.

PMID- 11250344
TI  - Acute and chronic onset of bronchiolitis obliterans syndrome (BOS): are they
      different entities?

PMID- 11250343
TI  - A murine model of left ventricular tissue engineering.

PMID- 11250345
TI  - Systemic but not cardiac expression of P-selectin and ICAM-1 mediate coronary
      microcirculatory changes in cardiac transplant recipients.

PMID- 11250346
TI  - Viral genome in the myocardium and outcomes in heart transplant recipients.

PMID- 11250347
TI  - The growth enhancing effects of allograft inflammatory Factor-1 (AIF-1) in VSMC
      are dose-dependent and mediated by its ability to bind calcium.

PMID- 11250348
TI  - Association of viral genome with transplant coronary arteriopathy and graft loss
      in children following cardiac transplantation.

PMID- 11250350
TI  - Donor or recipient origin of post transplant lymphoproliferative disease after
      lung transplantation.

PMID- 11250349
TI  - Patients at risk for post-transplant lymphoproliferative disease can be
      identified in the first months after lung transplantation by quantitative
      competitive-EBV-PCR.

PMID- 11250351
TI  - EBV mismatching and HLA matching post lung transplantation: key risk factors for
      post transplant lymphoproliferative disease(PTLD).

PMID- 11250352
TI  - Frequent monitoring of Epstein-Barr virus DNA load in unfractionated whole blood
      is essential for early detection of post-transplant lymphoproliferative disease
      in lung transplant patients.

PMID- 11250353
TI  - Antiviral prophylaxis prevents lymphoprofilerative disease in lung transplant
      recipients.

PMID- 11250354
TI  - Monthly infusion of cytomegalovirus immune globulin (CMVIG) decreases the
      incidence of bacterial and fungal infections in the first year following lung
      transplantation.

PMID- 11250355
TI  - Clinical experience with nine patients supported by the continuous flow Debakey
      VAD.

PMID- 11250356
TI  - Initial experience with the Jarvik 2000 left ventricular assist system as a
      bridge to transplantation: report of 4 cases.

PMID- 11250358
TI  - Assessment of myocardial recovery using dobutamine stress echocardiography in
      LVAD patients.

PMID- 11250357
TI  - Multicenter clinical evaluation of the heartmate; vented electric left
      ventricular assist system in patients awaiting heart transplantation.

PMID- 11250359
TI  - Does unloading the heart by a left ventricular assist device result in sustained
      reversal of myocyte dysfunction in end-stage heart failure?

PMID- 11250360
TI  - Predictive factors for weaning from a cardiac assist device. An analysis of
      clinical, gene expression, and protein data.

PMID- 11250361
TI  - Long-term post-transplant quality of life outcomes in patients bridged to
      transplant with ventricular assist devices.

PMID- 11250363
TI  - Health-promoting lifestyle and quality of life in long-term cardiac transplant
      recipeints.

PMID- 11250362
TI  - Change in physical and psychosocial domains of quality of life from before to
      after discharge post left ventricular assist device implantation.

PMID- 11250364
TI  - Heart transplantation in the older recipient: has the time come to reconsider our
      selection policies?

PMID- 11250365
TI  - Functional status and medical complications during the first year post lung
      transplantation (LTX).

PMID- 11250366
TI  - Assessment of coronary microcirculation in cardiac allografts. a comparison of
      intracoronary physiology, intravascular ultrasound and histological morphometry.

PMID- 11250367
TI  - Correlation between the glomerular filtratiion rate (GFR), serum creatinine
      (SCR), creatinine clearance (CRCL) and the calculated creatinine clearance (CALC
      CRCL) in heart transplant (HTX) patients (PTS).

PMID- 11250368
TI  - Panel reactive antibody screening practices prior to heart transplantation.

PMID- 11250369
TI  - Even slightly impaired kideny function (creatinine>1.79 MMOL/L) one year after
      cardiac transplantation has a negative impact on long term survival.

PMID- 11250371
TI  - Influence of graft ischemia time on outcomes following lung transplantation.

PMID- 11250370
TI  - Procalcitonin: a donor-specific predictor of early graft failure and early graft
      failure mortality after heart transplantation.

PMID- 11250372
TI  - Extended lung preservation with UW solution does not adversely affect graft
      outcome.

PMID- 11250373
TI  - The use of ABO compatible non-identical organs for cardiac transplantation: are
      we treating potential recipients with blood group O fairly?

PMID- 11250374
TI  - Utility of sublingual tacrolimus in cystic fibrosis patients after lung
      transplantation.

PMID- 11250375
TI  - Comparison of total lymphoid irradiation (TLI) versus tacrolimus for the
      treatment of obliterative bronchiolitis (OB) in lung transplants.

PMID- 11250376
TI  - Exhaled no (ENO) after lung transplantation (LTX): a prospective study.

PMID- 11250377
TI  - A multicenter study to assess outcome following a switch in the primary
      immunosuppressant from cyclosporin (CYA) to tacrolimus (TAC) in lung recipients.

PMID- 11250378
TI  - Hospital transfer of patients for LVAD bridge to transplant: is timing really
      critical to success?

PMID- 11250379
TI  - Timing of VAD bridging critical for outcome of adult heart transplantation.

PMID- 11250380
TI  - Hemodynamic exercise testing reveals a low incidence of myocardial recovery in
      LVAD patients.

PMID- 11250381
TI  - Altered expression of tyrosine kinase receptors Her2/neu and GP130 following left
      ventricular assist device (LVAD) placement in patients with heart failure.

PMID- 11250382
TI  - Mechanical unloading causes recovery of calcium cycling in the failing human
      heart.

PMID- 11250384
TI  - LVAD treated heart recipients do not have deleterious HLA antibody.

PMID- 11250383
TI  - Evolution and significance of HLA allosensitization during ventricular assist
      device support.

PMID- 11250386
TI  - Mechanical unloading decreases the expression of beta-tubulin in the failing
      human heart.

PMID- 11250387
TI  - Determinants of early graft failure following cardiac transplantation, a 10-year,
      multi-institutional, multivariable analysis.

PMID- 11250385
TI  - Allosensitization following left ventricular assist device (LVAD) implantation is
      dependent on CD40-CD40 ligand interactions.

PMID- 11250388
TI  - Older recipient age is associated with reduced alloreactivity and graft rejection
      after cardiac transplantation.

PMID- 11250389
TI  - Wall motion assessment by tissue Doppler imaging after heart transplantation:
      timing of endomyocardial biopsies and facilitation of therapeutic decisions
      during acute cardiac rejection.

PMID- 11250390
TI  - Intravenous immunoglobulin therapy in highly sensitized cardiac allograft
      recipients facilitates transplantation across donor specific IGG positive cross
      matches.

PMID- 11250391
TI  - The effect of interleukin-6 gene polymorphisms on the outcome of cardiac
      transplantation.

PMID- 11250392
TI  - Total depletion and suppression of natural and induced anti-pig antibodies in
      baboons.

PMID- 11250393
TI  - Low expression of ecto-5'-nucleotidase in the pig heart - a potential barrier to
      xenotransplantation.

PMID- 11250394
TI  - Computerized heart allograft recipient monitoring (CHARM) - a multicenter study.

PMID- 11250395
TI  - The TCR repertoire of proliferating T cells is restricted by immunodominant
      antigens in the direct human anti-pig pathway.

PMID- 11250396
TI  - Human T cells express CD86 and acquire APC function after stimulation with human
      or porcine APC.

PMID- 11250397
TI  - Systemic vasculitis complicating pig to primate xenotransplantation.

PMID- 11250398
TI  - Histopathology of rejection in the pig-to-primate cardiac xenograft model.

PMID- 11250400
TI  - Determinants of poor long-term survival after partial left ventriculectomy in
      patients with dilated cardiomyopathy.

PMID- 11250399
TI  - Cardiac resynchronisation therapy for advanced heart failure.

PMID- 11250401
TI  - Efficacy trends of the acorn cardiac support device in patients with heart
      failure: a one year follow-up.

PMID- 11250402
TI  - Myosplint implantation and ventricular shape change in patients with dilative
      cardiomyopathy- first clinical experience.

PMID- 11250403
TI  - Surgical management of severe emphysema in Australia: lung transplant and lung
      volume reduction surgery.

PMID- 11250404
TI  - Surgical therapy for chronic thromboembolic pulmonary hypertension: criteria for
      choosing lung transplant vs trhomboendarterectomy.

PMID- 11250405
TI  - FAS-FAS ligand death pathway does not contribute to CTL-mediated apoptosis of
      mouse vascular endothelium.

PMID- 11250406
TI  - Upregulation of PAI-1 is mediated through TGF beta /SMAD pathway in transplant
      arteriopathy.

PMID- 11250407
TI  - Depletion of recipient CD8+ T cells does not alter the development of cardiac
      allograft vasculopathy.

PMID- 11250408
TI  - Anti-CD25 therapy affects the death signals of activated T-cells after clinical
      heart transplantation.

PMID- 11250409
TI  - Nitric oxide regulates the apoptotic pathway in explanted failing human hearts.

PMID- 11250410
TI  - Interleukin-10 gene targeting induced apoptosis of alloractive T cell via
      FAS/FASL pathway.

PMID- 11250411
TI  - Pediatric lung transplantation and CMV pneumonitis: a ten year experience.

PMID- 11250412
TI  - Lung transplantation in children following treatment for mallignancy.

PMID- 11250413
TI  - Interleukin-2-receptor blockade with daclizumab decreases the incidence of acute
      rejection in pediatric lung transplant recipients.

PMID- 11250414
TI  - Comparison of pretransplant transfusion with or without cyclosporin inhibition on
      post transplant outcome.

PMID- 11250415
TI  - Graft accommodation in infant recipients of ABO-incompatible heart transplants:
      donor ABH antigen expression in graft biopsies.

PMID- 11250416
TI  - Clinical outcome after starting carvedilol in infants and children with severe
      dilated cardiomyopathy candidates for heart transplantation.

PMID- 11250417
TI  - Coronary artery revascularization in eligible lung transplant recipients.

PMID- 11250419
TI  - A cluster of mycoplasma hominis infection in heart-lung transplantation.

PMID- 11250420
TI  - Hepatitis C virus infection after lung transplantation: dim prognosis.

PMID- 11250418
TI  - A classification system for severity of lung dysfunction after lung
      transplantation: a predictor of outcome.

PMID- 11250421
TI  - Impact of antibiotic-resistant pseudomonas on the survival of cystic fibrosis
      (CF) patients following heart-lung transplantation.

PMID- 11250422
TI  - BLTX with intra- and postoperatively prolonged ECMO in patients with pulmonary
      hypertension: beneficial effect on initial organ function.

PMID- 11250423
TI  - Intervention prevents progression of osteoporosis in patients awaiting lung
      transplantation.

PMID- 11250424
TI  - Prevalence of sleep disordered breathing after lung transplantation.

PMID- 11250425
TI  - Pregnancy after heart-lung transplantation.

PMID- 11250426
TI  - Single lung transplantation for pulmonary alveolar microlithiasis.

PMID- 11250427
TI  - Impaired vasodilation during endothelin-A receptor blockade in lung transplanted
      patients.

PMID- 11250428
TI  - Angiotensin II induces PAI-1 expression through MAP kinase-dependent, but TGF
      beta and PI3 kinase-independent pathway.

PMID- 11250429
TI  - Apoptosis in cardiac allograft rejection and its response to treatment.

PMID- 11250430
TI  - Hepatic source of C6 drives complement-mediated cardiac allograft injury.

PMID- 11250431
TI  - HMG-COA reductase inhibitor cerivastatin prolonged rat cardiac allograft survival
      by blocking intercellular signals.

PMID- 11250432
TI  - CD8+ lymphocytes participate in the development of chronic rejection.

PMID- 11250433
TI  - Inducible expression of basic transcription factor binding protein 2 plays a
      potential role in the development of the allograft vascular disease.

PMID- 11250434
TI  - The impact of CD4 and CD8 transendothelial migration in the development of
      transplant arteriosclerosis following experimental cardiac transplantation.

PMID- 11250435
TI  - FK506 vs. cyclosporin: pathologic findings in 1067 endomyocardial biopsies.

PMID- 11250436
TI  - Sudden, unexpected death in cardiac transplant recipients: an autopsy study.

PMID- 11250437
TI  - Use of en face silver nitrate staining to assess endothelial gaps and vascular
      permeability in rat coronary artery transplant vasculopathy.

PMID- 11250438
TI  - Alloregulatory T cells producing TGFB/IL10 can be generated ex vivo.

PMID- 11250439
TI  - Safety and efficacy of pravastatin in pediatric heart transplant recipients.

PMID- 11250440
TI  - Efficacy and safety of atorvastatin after pediatric cardiac transplantation.

PMID- 11250441
TI  - Invasive pneumoccoccal infection in pediatric heart transplant patients.

PMID- 11250442
TI  - Twelve year experience with pediatric cardiac retransplantation.

PMID- 11250443
TI  - Preliminary experience with IVUS in pediatric heart transplant recipients.

PMID- 11250444
TI  - Is renal function in paediatric heart transplant recipients influenced by late
      reduction in cyclosporine dosage?

PMID- 11250445
TI  - Specialized, comprehensive care eliminates racial and gender differences in
      mortality between African American and Caucasian heart failure patients.

PMID- 11250446
TI  - Dobutamine/atropine stress echocardiography: feasibility, safety and early
      results in paediatric heart transplant recipients.

PMID- 11250447
TI  - Humoral and echo-Doppler parameters in predicting the benefits of betablockers in
      patients with dilated cardiomyopathy.

PMID- 11250448
TI  - Improvement of acute renal dysfunction (ARD) in heart transplant (TX) patients
      (PTS) during calcineurin inhibitor (CNI) 'holiday' without rejection under anti
      CD25 monoclonal antibody (MAB) coverage.

PMID- 11250449
TI  - Prevention of accelerated rejection and prolonged survival in sensitized rats
      with cyclophosphamide therapy.

PMID- 11250450
TI  - In vivo effect of sirolimus on T cells, B cells and monocytes in non-human
      primates.

PMID- 11250451
TI  - Cyclosporine does not enhance the development of chronic rejection. Experimental
      study in a rat cardiac transplant model.

PMID- 11250452
TI  - Membrane transport of mycophenolate mofetil and its active metabolite,
      mycophenolic acid in MDCK and MDR1-MDCK cell monolayers.

PMID- 11250453
TI  - Comparative study of CSA and FK506 versus newer immunosuppressive drugs MMF and
      rapamycin on coronary endothelial function in vitro.

PMID- 11250454
TI  - The diminishing impact of pretransplant pulmonary hypertension on perioperative
      mortality after cardiac transplantation.

PMID- 11250455
TI  - MMF-a new cornerstone in immunosuppressive therapy after cardiac transplantation.

PMID- 11250456
TI  - Statins improve long-term survival and reduce incidence of hemodynamically
      significant rejection.

PMID- 11250457
TI  - The value of exhaled co-measurement for detection of smoking after heart
      transplantation.

PMID- 11250458
TI  - Longer distance from transplant center is not associated with decreased survival
      in post cardiac transplant patients.

PMID- 11250459
TI  - Preoperative amiodarone increases risk of bleeding complications following
      cardiac transplantation.

PMID- 11250460
TI  - Ventricular asynchrony after heart transplantation: prevalence and clinical
      correlates.

PMID- 11250461
TI  - Monoclonal gammopathy in heart transplantation: clinical significance and risk
      factors.

PMID- 11250462
TI  - Is outcome after heart transplantation influenced by ethnicity? A comparison of
      African Americans versus Caucasians.

PMID- 11250463
TI  - Myocardial ischemic injury following heart transplantation is associated with
      decreased risk of acute cellular rejection in the absence of humoral rejection.

PMID- 11250464
TI  - Procalcitonin (PCT) is a new biological marker for the diagnosis of non-viral
      infections after transplantation of intrathoracic organs.

PMID- 11250466
TI  - Extracorporeal membrane oxygenation for neonates with single ventricle and
      parallel circulations.

PMID- 11250465
TI  - The internal cardiac defibrillator for VT on LVAD support.

PMID- 11250467
TI  - Effect of the abiocor implantable replacement heart on immune system function.

PMID- 11250469
TI  - Improved myocardial structure following LVAD support: effect of unloading on
      dystrophin expression.

PMID- 11250468
TI  - Native ventricular performance after one year of left ventricular support.

PMID- 11250470
TI  - LVAD blood stream infection: therapeutic rationale for transplantation.

PMID- 11250471
TI  - LVAD therapy improves utilization of donor hearts: implications for prolonged
      inotropic therapy.

PMID- 11250472
TI  - Nitric oxide inhalation modulates endothelin-1 and big endothelin-1 after left
      ventricular assist device implantation.

PMID- 11250473
TI  - Changes in the solid organ donor pool and the effect on cardiothoracic donation?

PMID- 11250474
TI  - Predictors of death on the UNOS lung transplant waiting list: results of a
      multivariate analysis.

PMID- 11250475
TI  - The impact of changes in radiographic abnormalities in organ donors on successful
      lung donation.

PMID- 11250476
TI  - Systolic right ventricular dysfunction in 'good' donor hearts- a normal finding?

PMID- 11250477
TI  - Ratings of children's self perception before and one year after transplantation:
      do children and their parents agree?

PMID- 11250478
TI  - Optimizing heart transplant patient education: is once enough?

PMID- 11250479
TI  - The dilemma of disability after heart transplantation.

PMID- 11250480
TI  - Heart failure (HF): are nurses providing patients with optimal education of self
      care principles?

PMID- 11250482
TI  - Diabetes related complications in patients after heart transplantation.

PMID- 11250481
TI  - Pediatric living donor lung transplantation: psychosocial considerations.

PMID- 11250483
TI  - Diabetes affects long-term survival after heart transplantation.

PMID- 11250484
TI  - Right atrial geometry and tricuspid regurgitation after orthotopic heart
      transplantation: benefits of a modified biatrial surgical technique.

PMID- 11250485
TI  - Incidence of erectile dysfunction and efficacy of sildenafil in the cardiac
      transplantation patient.

PMID- 11250486
TI  - A randomised controlled trial of antihypertensive treatment with valsartan after
      heart transplantation.

PMID- 11250487
TI  - Optimal management of severe tricuspid regurgitation in cardiac transplant
      recipients.

PMID- 11250488
TI  - Immunologic events and long term survival after combined heart and kidney
      transplantation : a twelve-year single-center experience.

PMID- 11250489
TI  - Reversal of chronic cyclosporin nephrotoxicity after heart transplantation.

PMID- 11250490
TI  - Outcome of heart transplant in patients with renal insufficiency.

PMID- 11250491
TI  - Pituitary stimulation in cardiac transplant recipients with low free testosterone
      levels.

PMID- 11250492
TI  - Mouse vascular endothelium activates alloreactive CD8+ T lymphocytes in B-7
      dependent fashion.

PMID- 11250493
TI  - European multicenter tacrolimus heart pilot study: three year follow-up.

PMID- 11250494
TI  - Hypotensive reactions associated with transfusion of bedside leukocyte reduction
      filtered blood products in heart transplanted patients.

PMID- 11250495
TI  - Monotherapy with anti-CD40 ligand antibody (IDEC 131) for non-human primate
      allograft heart transplantation.

PMID- 11250496
TI  - Is carvedilol safe and efficaceous in severe heart failure patients accepted for
      heart transplantation?

PMID- 11250497
TI  - Swan Ganz catheter assessment of donor hearts - outcome of organs with borderline
      haemodynamics.

PMID- 11250498
TI  - Metoprolol reduces sympathetic nerve hyperactivity in patients with heart
      failure.

PMID- 11250499
TI  - B-type natriuretic peptides (BNP and PRO-BNP) predict longterm survival in
      patients with advanced heart failure treated with atenolol.

PMID- 11250500
TI  - Are beta blockers effective in African Americans with systolic heart failure?

PMID- 11250501
TI  - CD28/B7-2 pathway regulates the development of experimental obliterative
      bronchiolitis via promotion of TH1 cytokine expression.

PMID- 11250502
TI  - Beta-blocker therapy reduces mortality on the waiting list for cardiac
      transplantation.

PMID- 11250503
TI  - Survival benefit of the implantable cardioverter/defibrillator in patients listed
      for cardiac transplantation.

PMID- 11250504
TI  - MMF significantly reduces the transendothelial migration of graft infiltrating
      leucocytes.

PMID- 11250505
TI  - Fluvastatin in combination with RAD significantly reduces transplant coronary
      vasculopathy in rat cardiac allografts.

PMID- 11250506
TI  - Systemic administration of recombinant human relaxin (RHRLX) ameliorates the
      acute cyclosporine nephrotoxicity in rats.

PMID- 11250507
TI  - NKH477, a forskolin derivative, exerts an antiproliferative effect in vivo with
      an altered cytokine profile in rat recipients of orthotopic lung allografts.

PMID- 11250508
TI  - 1,25-dihydroxycholecalciferol reduces acute rejection in rat lung
      allotransplantation.

PMID- 11250509
TI  - A randomized trial of inhaled nitric oxide to prevent reperfusion injury
      following lung transplantation.

PMID- 11250510
TI  - A positive donor gram stain does not predict the development of pneumonia,
      oxygenation, or duration of mechanical ventilation following lung
      transplantation.

PMID- 11250511
TI  - Pulmonary vein gas analysis for assessing of donor lung function.

PMID- 11250512
TI  - Empirical supportive therapy in the hypotensive donor - best guess or worst
      option?

PMID- 11250513
TI  - Use of hearts transplanted from donors with atraumatic intracranial bleeds.

PMID- 11250514
TI  - Evaluation of extended donor and recipient criteria for lung transplantation.

PMID- 11250515
TI  - Long-term renal function in heart transplant recipients receiving tacrolimus
      (FK506) therapy.

PMID- 11250517
TI  - Influence of methilenethetraidrofolate reductase polymorphism on total
      homocysteine plasma levels in heart transplant recipients.

PMID- 11250516
TI  - Prevention of osteoporosis in cardiac transplant recipients.

PMID- 11250518
TI  - Immediate renal replacement therapy and outcome after cardiac transplantation - a
      multivariate analysis of risk factors.

PMID- 11250519
TI  - Posttransplantation lymphoproliferative disease in heart and heart-lung
      transplant recipients: thirty years experience at our hospital.

PMID- 11250520
TI  - Transbronchial lung biopsy for acute rejection is a safe procedure in lung
      transplant recipients.

PMID- 11250521
TI  - Diagnostic yield of follow-up transbronchial lung biopsies after acute rejection
      in lung transplant recipients.

PMID- 11250522
TI  - Success of lung transplantation without surveillance bronchoscopy.

PMID- 11250523
TI  - Non-immune acute graft injury after lung transplantation and the risk of
      subsequent bronchiolitis obliterans syndrome (BOS).

PMID- 11250524
TI  - Hypertonic saline challenge predicts early onset bronchiolitis obliterans
      syndrome post-lung transplantation.

PMID- 11250525
TI  - Bronchoalveolar lavage(BAL) neutrophilia in lung transplant recipients(LTR):
      infection and bronchiolitis obliterans syndrome(BOS), the chicken or the egg?

PMID- 11250526
TI  - Death after cardiac transplantation in low birth weight neonates.

PMID- 11250527
TI  - Intrathoracic organ transplantation in adults with congenital heart disease.

PMID- 11250528
TI  - Transplant coronary artery disease in pediatrics: favorable outcome with medical
      therapy.

PMID- 11250529
TI  - Outcome after diagnosis of moderate-severe transplant coronary artery disease
      (TCAD) in pediatric heart transplant recipients.

PMID- 11250530
TI  - Effects of the dual endothelin receptor antagonist bosentan in patients with
      pulmonary hypertension: a placebo-controlled study.

PMID- 11250531
TI  - Paediatric heart transplantation in the United Kingdom - a five year review of
      practice and results.

PMID- 11250532
TI  - Interaction of volume and era on survival of children listed for cardiac
      transplantation.

PMID- 11250533
TI  - The DD5 gene of the decapod crustacean Penaeus japonicus encodes a putative
      exoskeletal protein with a novel tandem repeat structure.
AB  - A gene, named DD5, was identified in the penaeid prawn Penaeus japonicus and its
      cDNA cloned and sequenced. DD5 is expressed in the epidermal cells underlying the
      exoskeleton and the transcripts are detected specifically during the postmolt
      stage of the molt cycle. Sequence analysis of the conceptual protein product
      suggests that the DD5 protein is a component of the exoskeleton. The bulk of the
      protein consists of tandem repeats of a unit sequence of approximately 100 amino
      acids. The repeated sequences are highly homologous to one another and each of
      them includes a variant of the Rebers--Riddiford consensus sequence.

PMID- 11250534
TI  - Soluble proteins of the nacre of the giant oyster Pinctada maxima and of the
      abalone Haliotis tuberculata: extraction and partial analysis of nacre proteins.
AB  - Several proteins from nacre of the oyster Pinctada maxima and the abalone
      Haliotis tuberculata were extracted and partly characterized. Proteins dispersed
      in aragonite were solubilized during demineralization with acetic acid whereas
      proteins adsorbed on conchiolin were extracted with sodium dodecyl sulfate and
      beta-mercaptoethanol. The matrix of Pinctada maxima nacre is composed of one main
      protein with an apparent molecular weight of 20 kDa (p20). This protein was found
      in the acetic acid soluble fraction of nacre, as well as in the Laemmli
      solubilized extract of conchiolin. In addition, the p20 solubilized with acetic
      acid can form oligomers made of 6 monomers linked together by disulfide bridges.
      The first N-terminal 21 amino acids of p20 were determined and no homology with
      known proteins was found. In Haliotis tuberculata nacre, 5 main proteins were
      solubilized during demineralization and 3 glycoproteins were detected. Stains-all
      and Alcian blue staining revealed polyanionic proteins in the extracts isolated
      from Pinctada maxima and Haliotis tuberculata nacre.

PMID- 11250535
TI  - Cloning of glycerol-3-phosphate dehydrogenase cDNAs from two fish species and
      effect of temperature on enzyme expression in rainbow smelt (Osmerus mordax).
AB  - Rainbow smelt (Osmerus mordax) can accumulate extreme levels of glycerol in their
      blood during winter. Low temperatures are required for glycerol accumulation in
      smelt blood and the enzyme glycerol-3-phosphate dehydrogenase (GPDH) has been
      suggested to play a role in glycerol production/concentration in this species. In
      the present study, cDNA sequences encoding glycerol-3-phosphate dehydrogenase
      (GPDH) from rainbow smelt and Atlantic salmon (Salmo salar) were cloned. The
      encoded GPDH protein sequences were very similar to one another (88% identity).
      Using RT-PCR, GPDH mRNA was detected in skin, gill, heart, head kidney, brain and
      liver from both salmon and smelt obtained in December. However, GPDH was not
      detected in salmon intestine and spleen or in smelt intestine. Examination of
      GPDH expression in smelt liver during February by Northern blotting revealed
      temperature regulation. Elevation of the temperature resulted in a significant
      decrease in liver GPDH transcript level. Serum glycerol levels decreased
      concomitantly. These findings suggest a role for GPDH in the accumulation of
      glycerol in smelt at low temperatures.

PMID- 11250536
TI  - Characterization of hepatic low-K(m) outer-ring deiodination in red drum
      (Sciaenops ocellatus).
AB  - The more biologically active thyroid hormone 3,5,3'-triiodothyronine (T(3)), is
      primarily derived from peripheral deiodination of thyroxine (T(4)). We
      characterized hepatic deiodination for a commercially important, warm water
      teleost fish, the red drum (Sciaenops ocellatus). Low K(m) outer-ring
      deiodination (ORD) activity was determined by production of free iodide ((125)I)
      upon incubation of hepatic microsomes with radiolabeled T(4). HPLC analysis
      demonstrated that (125)I, and T(3) were produced in equal amounts, thereby
      validating 125I as a measure of T(3) production. A small amount of 3,3',5'
      triiodothyronine (reverse T(3)) was also produced by inner-ring deiodination.
      Production of (125)I was linear over a range of 0--100 microg protein/ml and for
      incubations of 30 min--4 h. Maximal ORD activity was measured at pH 6.6, 50 mM
      dithiothreitol (DTT) and an incubation temperature of 20 degrees C. Double
      reciprocal plots demonstrated that the average apparent K(m) was 5.1 nM and the
      average V(max) was 3.7 pmol T(4) converted/h per mg protein. ORD was not
      inhibited by propylthiouracil but was 50% inhibited by 90 microM of iodoacetic
      acid and 7 microM of gold thioglucose. The substrate analog preference was T(4) =
      tetraiodoacetic acid = reverse T(3) > triiodoacetic acid >> T(3). In relation to
      other tissues, ORD for liver>gill>intestine>kidney. Similar hepatic deiodination
      activity was present in adult wild, aquacultured and laboratory-reared red drum,
      but in adult wild red drum the optimum temperature was higher. Red drum hepatic
      low-K(m) deiodination activity appears to most closely resemble rainbow trout
      hepatic and mammalian Type II deiodination. Evidence of inner-ring T(4)
      deiodination suggests a more active hepatic iodothyronine catabolic pathway than
      in other teleost species.

PMID- 11250537
TI  - Co-ordinated induction of beta-carotene cleavage enzyme and retinal reductase in
      the duodenum of the developing chicks.
AB  - The developmental patterns of expression of beta-carotene cleavage enzyme
      activity were compared with those of retinal reductase and NAD-dependent retinol
      dehydrogenase activities in chick duodenum during the perinatal period. The beta
      carotene cleavage enzyme activity was not detected in the duodenum before
      hatching, but it increased rapidly during 24 h after hatching. On the other hand,
      a considerable level of beta-carotene cleavage enzyme activity was observed in
      the liver of embryonic stages and its activity gradually rose during the
      perinatal period. Comparison of kinetic constants for the beta-carotene cleavage
      enzyme activities in the duodenum and the liver indicated that the enzyme in the
      duodenum possessed a lower affinity for beta-carotene than that in the liver. The
      retinal reductase activity was detected in the microsomes of the duodenum at the
      earliest time examined, i.e. day 16 of embryogenesis and its activity began to
      rise on the last day of embryogenesis, which was followed by a gradual increase
      until 1 day of age. The NAD-dependent retinol dehydrogenase activity was also
      seen in the microsomes of the duodenum in embryonic stages and its activity
      increased in parallel with the retinal reductase activity around the hatching
      period. These developmental inductions of beta-carotene cleavage enzyme and
      retinal reductase activities in the duodenum coincided with those of cellular
      retinol-binding protein, type II (CRBPII) and lecithin: retinol acyltransferase
      (LRAT). These results suggest that a co-ordinated induction mechanism should be
      operative for beta-carotene cleavage enzyme and retinal reductase, both of which
      are inevitable in the process of beta-carotene absorption and metabolism.

PMID- 11250538
TI  - Metabolic characteristics of muscles in the spiny lobster, Jasus edwardsii, and
      responses to emersion during simulated live transport.
AB  - The metabolic characteristics of five muscle groups in the spiny lobster Jasus
      edwardsii were examined in order to compare their anaerobic and oxidative
      capacities. Enzyme activities of phosphorylase, phosphofructokinase, pyruvate
      kinase, and lactate dehydrogenase were highest in abdominal muscles supporting
      anaerobic burst activity. Hexokinase, citrate synthase, and HOAD activities in
      the leg and antennal muscles indicated higher aerobic potential. Arginine kinase
      activities were high in all muscle groups indicating that muscle phosphagens are
      an important energy reserve. Arginine phosphate concentrations in 4th periopod
      and abdominal flexor muscle from lobsters sampled in the field were higher than
      any values from captive animals, and approximately five times those for ATP.
      Muscle lactates were high in captive animals. Responses to emersion during
      simulated live transport appear to exploit the capacity for functional
      anaerobiosis and further differentiated the muscle groups. Abdominal muscles were
      especially sensitive and after 24 h showed significant increases in lactate,
      glucose, ADP, and AMP. ATP levels appeared to be maintained by muscle phosphagens
      and raised doubts about the efficacy of the adenylate energy charge in evaluating
      the emersion response. Haemolymph glucose, lactic acid, and ammonia peaked after
      24 h emersion and were largely restored following re-immersion. We propose that
      arginine phosphate concentrations in the 4th periopod are an appropriate index of
      metabolic stress, and could lead to improved commercial handling protocols.

PMID- 11250539
TI  - Purification and characterization of the fatty acid synthase from Bugula
      neritina.
AB  - The fatty acid synthase from Bugula neritina has been purified 100-fold using
      ammonium sulfate precipitation, ion-exchange and size exclusion chromatography.
      The purified enzyme has a molecular weight of approximately 382,000 Da, as judged
      by gel filtration. Polyacrylamide gel electrophoresis under denaturing conditions
      in the presence of SDS revealed one major protein band of approximately 190,000
      Da suggesting that the enzyme is a homodimer. The size of the enzyme, together
      with the observation that the FAS activity is independent of the concentration of
      acyl carrier protein, indicate that the FAS from Bugula neritina is a type I. A
      detailed analysis of the products of the purified FAS indicated that palmitic
      acid is the primary product and longer chain fatty acids are not produced.

PMID- 11250540
TI  - Variability of sperm specific histones in sea urchins.
AB  - The variability of sperm histones was compared in two species of sea urchin.
      Whole sperm specific histones (SpH), were isolated from Tetrapygus niger
      (Arbacoida) and Parechinus angulosus (Echinoida). Individual histones were
      purified by chromatography on BioGel P-60 followed by reverse high pressure
      liquid chromatography (HPLC). The heterogeneity of each major histone type from
      T. niger was established from their HPLC elution patterns and further confirmed
      by electrophoresis in polyacrylamide gels containing 6 mM Triton X-100 combined
      with a transverse urea gradient (0--8 M). In T. niger, as well as in P.
      angulosus, a single form of SpH1 and SpH2A were found. In contrast, SpH2B was
      found to be heterogeneous, but represented by one major form in both species. The
      relatedness between both sets of histones was determined by establishing their
      immunological cross-reactivity. In this context, polyclonal antibodies elicited
      against T. niger sperm histones were assayed against individual histones from P.
      angulosus. From the results obtained, it emerged that histone SpH2A was the more
      closely related protein between these two species, followed by histone SpH1. In
      contrast, histone SpH2B was found to be only moderately related. These results
      confirm that SpH2A did not co-evolve with SpH2B, as was predicted for most
      species.

PMID- 11250541
TI  - Transcript analysis of the genes encoding aminopeptidase N and alanine
      aminotransferase, two enzymes involved in protein turnover, in the Pacific
      oyster, Crassostrea gigas.
AB  - Molecular probes have been developed to detect aminopeptidase N (ApN) and alanine
      aminotransferase (ALAT) transcripts in the Pacific oyster Crassostrea gigas.
      Degenerate primers were designed using ApN and ALAT sequences stored in the EMBL
      database. Amplification of C. gigas genomic DNA using these primers resulted in
      amplification of a 344-bp ApN fragment and a 530-bp alanine aminotransferase
      fragment. The deduced amino acid sequence of the ApN fragment displayed 75 and
      73% identities with sequences of ApN from human and mouse, respectively. The
      deduced amino acid sequence of the ALAT fragment displayed 57% identity both with
      human and rat ALAT. An ApN transcript of approximately 3.1 kb was detected by
      northern blotting in larvae and in adult digestive gland and gonadal tissue. No
      transcript was detected in adult adductor muscle. An ALAT transcript of
      approximately 2 kb was similarly detected in larvae and in adult gonadal tissue,
      but was undetectable in adult digestive gland and adductor muscle. Transcript
      detection employing RT-PCR demonstrated low-level expression of both ApN and ALAT
      in all studied tissues, in both larvae and adults.

PMID- 11250542
TI  - Sequence analysis of the aminoacylase-1 family. A new proposed signature for
      metalloexopeptidases.
AB  - The amino acid sequence analysis of the human and porcine aminoacylases-1, the
      carboxypeptidase S precursor from Saccharomyces cerevisiae, the succinyl
      diaminopimelate desuccinylase from Escherichia coli, Haemophilus influenzae and
      Corynebacterium glutamicum, the acetylornithine deacetylase from Escherichia coli
      and Dictyostelium discoideum and the carboxypeptidase G(2) precursor from
      Pseudomonas strain, using the Basic Local Alignment Search Tool (BLAST) and the
      Position-Specific Iterated BLAST (PSI-BLAST), allowed us to suggest that all
      these enzymes, which share common functional and biochemical features, belong to
      the same structural family. The three amino acid blocks which were found to be
      highly conserved, using the CLUSTAL W program, could be assigned to the catalytic
      active site, based on the general three-dimensional structure of the
      carboxypeptidase G(2) from the Pseudomonas strain precursor. Six additional
      proteins with the same signature have been retrieved after performing two
      successive PSI-BLAST iterations using the sequence of the conserved motif, namely
      Lactobacillus delbrueckii aminoacyl-histidine dipeptidase, Streptomyces griseus
      aminopeptidase, Saccharomyces cerevisiae aminopeptidase Y precursor, two Bacillus
      stearothermophilus N-carbamyl-L-amino acid amidohydrolases and Pseudomonas sp.
      hydantoin utilization protein C. The three conserved amino acid motifs
      corresponded to the following blocks: (i) [S, G, A]-H-x-D-x-V; (ii) G-x-x-D; and
      (iii) x-E-E. This new sequence signature is clearly different from that commonly
      reported in the literature for proteins belonging to the ArgE/DapE/CPG2/YscS
      family.

PMID- 11250543
TI  - Monosaccharide uptake in common carp (Cyprinus carpio) EPC cells is mediated by a
      facilitative glucose carrier.
AB  - In most animal cells, transport of monosaccharides across the plasma membrane is
      mediated by glucose transporters (GLUT). Mammals express at least five distinct
      transporters (GLUTs 1--5), which are well characterised both functionally and
      genetically. In contrast, the glucose transport system of fish remains poorly
      studied. Here we report studies of hexose uptake in carp EPC cells and cloning of
      a glucose transporter cDNA from these cells. Transport of radio-labelled
      methylglucose (3-OMG) followed Michaelis--Menten kinetics with a K(m) value (8.5
      mM) similar to that of mammalian cells. The inhibition of transport by
      cytochalasin B and phloretin, but not by phloridzin or cyanide, strongly
      suggested the existence of a facilitative carrier. D-Glucose, 2-deoxyglucose, 3
      OMG, D-mannose and D-xylose were competitive inhibitors of 3-OMG uptake, while L
      glucose, mannitol, D-fructose, D-ribose and sucrose did not compete with 3-OMG.
      We cloned a carp glucose transporter (CyiGLUT1), using RT-PCR and RACE
      strategies. CyiGLUT1 was different from known carp and zebrafish EST sequences.
      The complete cDNA (3060 bp) contained one open reading frame encoding a predicted
      protein of 478 amino acids. The deduced amino acid sequence shared 78% identity
      with mammalian and avian GLUT1 proteins. Key amino acids involved in substrate
      selection and catalysis of mammalian GLUTs were conserved in the carp
      transporter.

PMID- 11250544
TI  - Effects of L-thyroxine on incorporation of (32)P into phospholipids of freshwater
      eels.
AB  - The effects of L-thyroxine on phospholipid biosynthesis, via (32)P incorporation,
      were studied in gill, kidney, liver and muscle tissue of eels acclimatized at 11
      degrees C. L-thyroxine treatment had no effect on tissue content of lipid,
      inorganic and organic acid-soluble phosphorus. Only an increase of the specific
      radioactivities of lipid, inorganic and organic acid-soluble phosphorus was
      observed in the muscle. Percentage distribution of (32)P among classes of
      phospholipid were significantly altered in liver and muscle, without change in
      phospholipid composition. A specific effect of L-thyroxine on (32)P incorporation
      into phosphatidic acid in muscle and liver has been shown. As expected by the
      higher specific radioactivity of muscle inorganic and organic acid-soluble
      phosphorus, the increased incorporation of (32)P into phosphatidic acid probably
      results from a higher specific radioactivity of muscle ATP phosphorus.

PMID- 11250545
TI  - Effect of starvation on free histidine and amino acids in white muscle of
      milkfish Chanos chanos.
AB  - Milkfish (Chanos chanos) decreased their body weight from 47 to 28 g over the 60
      day period of starvation. Starvation also resulted in the reduction of muscle
      lipid and protein, and hepatosomatic index. The predominant free amino acid (FAA)
      in white muscle of milkfish was histidine, followed by taurine and glycine. In
      the first 25 days of starvation, no significant change in histidine was found.
      After 40 days of starvation, however, the histidine concentration was
      significantly decreased by 46%, and remained unchanged thereafter. As compared to
      control group fish, the 60-day-starved fish possessed only half the amount of
      histidine. Taurine and glycine, on the other hand, showed no significant changes
      throughout starvation. Taurine became the most predominant in the FAA pool after
      40 days of starvation, and the concentration of 60-day-starved fish was two times
      higher than that of control group fish without starvation. The ratios of
      histidine, taurine, and glycine to total FAAs remained approximately the same
      although the individual contributions varied considerably to the total FAAs
      during starvation. The results of this study suggested that a good strategy would
      be to keep taurine and glycine in milkfish muscle at relatively high levels for
      physiological function as histidine decreased drastically for energy source under
      conditions of food deprivation.

PMID- 11250547
TI  - Evolution of receptors for proglucagon-derived peptides: isolation of frog
      glucagon receptors.
AB  - The mammalian proglucagon gene encodes three glucagon-like sequences, glucagon,
      glucagon-like peptide 1 (GLP-1) and glucagon-like peptide 2 (GLP-2). Each of
      these three functionally distinct proglucagon-derived peptides has a unique, but
      related, receptor. To better understand the origin of the unique physiological
      functions of each proglucagon-derived glucagon-like sequence we have cloned
      glucagon-like receptors from two species of frogs, Xenopus laevis and Rana
      pipiens. The cloned glucagon-like receptor sequences were found to be most
      closely related to glucagon receptors. To determine whether the evolutionary
      history of the receptors for proglucagon-derived peptides was the same as that
      inferred for the peptide hormones, we conducted a phylogenetic analysis using
      both parsimony and distance methods. We show that the evolutionary history of the
      receptors for glucagon-like sequences differ from the history of the glucagon
      like sequences. The phylogeny of receptors for proglucagon-derived peptides is
      not monophyletic (i.e. they are not each other's closest relatives), as the
      receptor for the hormone glucose-dependent insulinotropic peptide (GIP) is more
      closely related to the glucagon receptor than either the GLP-1 or GLP-2
      receptors. In contrast to the evolutionary origin of glucagon-like sequences,
      where glucagon is of most ancient origin, we found that the GLP-2 receptor has
      the most ancient origin. These observations suggest that the diversification of
      the glucagon-like sequences encoded by the proglucagon gene and of the receptors
      for these peptides occurred independently, and that either these hormones or
      their receptors have been recruited for new functions.

PMID- 11250546
TI  - Biochemical properties of metalloproteinases from the hemolymph of the mussel
      Mytilus galloprovincialis Lam.
AB  - The expression of matrix metalloproteinases (MMP) with gelatinase activity was
      found in the whole hemolymph of the marine mussel Mytilus galloprovincialis Lam.
      Cleavage activity was specific for gelatin; very little activity towards human
      type-IV collagen, and no activity for cold fish gelatin, casein or bovine serum
      albumin were detected. EDTA and 1,10-phenanthroline were inhibitory, suggesting
      that mussel MMPs require divalent cations for their proteolytic activity; in
      fact, the presence of exogenously added divalent ions significantly protected the
      MMPs from inhibition. No inhibition was detected with serine or cysteine
      proteinase inhibitors. The specific vertebrate inhibitors as well as the
      classical vertebrate activator of MMPs were without effect, whereas sulphydryl
      reducing agents had a strong inhibitory effect. Mussel MMPs showed an exponential
      curve of thermal-dependent decay that was not protected by the presence of metal
      ions. Overall the results indicate both similarities and differences between
      invertebrate and vertebrate gelatinases, providing information for understanding
      the biological role of these ancient proteinases.

PMID- 11250548
TI  - Carotenoids in bird plumage: the complement of red pigments in the plumage of
      wild and captive bullfinch (Pyrrhula pyrrhula).
AB  - We have studied the carotenoid pigments in the red plumage of male bullfinch
      (Pyrrhula pyrrhula) immediately following capture and after the completion of the
      moult in captivity under dietary control. Astaxanthin, adonirubin, and alpha
      doradexanthin, as well as papilioeritrinone and canthaxanthin (in lower amounts)
      are in every case the dominant carotenoids in the plumage pigment of wild
      individuals. alpha-Doradexanthin is responsible for the reddish-rose colour,
      which captive individuals adopt after a diet consisting mainly of lutein as
      disposable carotenoid. The red pigmentation biogenesis of captive bullfinch is
      compared with those of other red pigmented Carduelinae in which male individuals
      usually lose the red colour in captivity, namely Carpodacus roseus, Carpodacus
      rubricilloides, Uragus sibiricus, Carduelis cannabina, Carduelis flammea, Loxia
      curvirostra and Pinicola enucleator.

PMID- 11250549
TI  - Purification of apolipoprotein H (beta 2-glycoprotein I)-like protein from human
      follicular fluid.
AB  - We purified a glycoprotein of molecular weight 50 kDa that has an N-terminal
      sequence similar to that of apolipoprotein H indicating that it is identical to
      or highly homologous to apolipoprotein H. There are indications that
      apolipoprotein H or its homologue may be involved in the fertilization process.
      Sperm motion was assessed employing computer-assisted semen analysis. The
      addition of the purified protein to prepared sperm samples from normospermic men
      increases significantly the straight line velocity (VSL) and the amplitude of
      lateral head displacement (ALH) but does not increase the number of progressively
      motile sperm.

PMID- 11250550
TI  - Starch digestion in tropical fishes: isolation, structural studies and inhibition
      kinetics of alpha-amylases from two tilapias Oreochromis niloticus and
      Sarotherodon melanotheron.
AB  - alpha-Amylases from the intestinal cavity of two tilapia species, Oreochromis
      niloticus (ONI-AMY) and Sarotherodon melanotheron (SME-AMY), were purified using
      ammonium sulfate precipitation, affinity chromatography and chromatofocusing
      procedures. The purification was approximately 100-fold. The amylolytic activity,
      specific activity, product distribution, pH and temperature profile of ONI-AMY
      and SME-AMY are quite similar. The molecular mass differs slightly: 56600 (ONI
      AMY) vs. 55500 (SME-AMY). As shown by isoelectric focusing analysis, both
      amylases contain two isoforms A and B with distinct pI: 7.2 (A) and 7.8 (B), vs.
      8.3 (A) and 8.8 (B), respectively. It was not possible to isolate B, since B
      converts into A with time. The kinetics of the inhibition of ONI-AMY and SME-AMY
      activity by alpha-, beta- and gamma-cyclodextrin (alpha-, beta- and gamma-CD)
      were investigated using amylose as the substrate. Statistical analysis of the
      kinetic data expressed using a general velocity equation and assuming rapid
      equilibrium showed that the inhibition is of the mixed noncompetitive type.
      Similar results were obtained with ONI-AMY and SME-AMY. beta- and gamma-CD are
      stronger inhibitors than alpha-CD. ONI-AMY and SME-AMY are then closely related
      and show the general features common to the members of the alpha-amylase class
      (family 13). They enable ONI and SME tilapias to digest starch in food.

PMID- 11250551
TI  - Interannual variations in the lipids of the Antarctic pteropods Clione limacina
      and Clio pyramidata.
AB  - Antarctic pteropods, Clione limacina (Order Gymnosomata) and Clio pyramidata
      (order Thecosomata), were collected near Elephant Island, South Shetland Islands,
      during 1997 and 1998. Total lipid was high in C. limacina (29--36 mg g(-1) wet
      mass) and included 46% of diacy1glyceryl ether (DAGE, as % of total lipid) for
      both 1997 and 1998. DAGE was not detected in C. pyramidata, which had mainly
      polar lipid and triacy1glycerol. 1-O-Alkyl glyceryl ethers (GE) derived from the
      DAGE consisted primarily of 15:0 and 16:0, with lower 17:0 and a17:0. The
      principal sterols of both pteropods included trans-dehydrocholesterol,
      brassicasterol, 24-methylenecholesterol, cholesterol and desmosterol. Levels of
      24-methylenecholesterol and desmosterol were lower in both pteropods in 1997
      compared to 1998. C. limacina had high levels of the odd-chain fatty acids 17:1(n
      -8)c and 15:0 in contrast to C. pyramidata. The previously proposed source of
      elevated odd-chain fatty acids in C. limacina is via propionate derived from
      phytoplankton DMPT; another possible source may be from thraustochytrids, which
      are common marine microheterotrophs. C. pyramidata had twice as much PUFA as C.
      limacina, largely due to higher 20:5(n--3). The PUFA 18:5(n--3) and very long
      chain fatty acids (C(24), C(26) and C(28) VLC-PUFA) were only detected in 1998
      pteropods. In comparison, 1996 samples of C. limacina contained lower DAGE
      levels, which also may reflect differences in diet and oceanographic conditions.
      Interannual variations in specific lipid biomarkers are discussed with respect to
      possible different phytoplankton food sources available in the AMLR survey area.

PMID- 11250552
TI  - Bacterial expression and characterization of starfish phospholipase A(2).
AB  - Phospholipase A(2) (PLA(2)) from the pyloric ceca of the starfish Asterina
      pectinifera showed high specific activity and characteristic substrate
      specificity, compared with commercially available PLA(2) from porcine pancreas.
      To investigate enzymatic properties of the starfish PLA(2) in further detail, we
      constructed a bacterial expression system for the enzyme. The starfish PLA(2)
      cDNA isolated previously (Kishimura et al., 2000b. cDNA cloning and sequencing of
      phospholipase A(2) from the pyloric ceca of the starfish Asterina pectinifera.
      Comp. Biochem. Physiol. 126B, 579-586) was inserted into the expression plasmid
      pET-16b and the PLA(2) protein was expressed in Escherichia coli BL21 (DE3) by
      induction with isopropyl-beta-D(-)-thiogalactopyranoside. The recombinant PLA(2)
      produced as inclusion bodies was dissociated with 8 M urea and 10 mM 2
      mercaptoethanol and renatured by dialyzing against 10 mM Tris--HCl buffer (pH
      8.0). Renatured PLA(2) was purified by subsequent column chromatographies on DEAE
      -cellulose (DE-52) and Sephadex G-50. Although an N-terminal Ser in the native
      starfish PLA(2) was replaced by an Ala in the recombinant PLA(2), the recombinant
      enzyme showed essentially the same properties as did the native PLA(2) with
      respect to specific activity, substrate specificity, optimum pH and temperature,
      and Ca(2+) requirement.

PMID- 11250554
TI  - Environmental adaptations as windows on molecular evolution.
AB  - Changes in gene regulation may play an important role in adaptive evolution,
      particularly during adaptation to a changing environment. However, little is
      known about the molecular mechanisms underlying adaptively significant variation
      in gene regulation. To address this question, we are using environmental
      adaptations in populations of a fish, Fundulus heteroclitus as a window into the
      molecular evolution of gene regulation. F. heteroclitus are found along the East
      Coast of North America, with populations distributed along a steep thermal
      gradient. At the extremes of the species range, populations have undergone local
      adaptation to their habitat temperatures. A variety of genes differ in their
      regulation between these populations. We have determined the mechanism
      responsible for changes in lactate dehydrogenase-B (Ldh-B) gene regulation. A
      limited number of mutations in the regulatory sequence of this gene result in
      changes in its expression. Both the phenotypic (increased LDH activity) and
      genotypic (changes in Ldh-B regulatory sequences) differences between populations
      have been shown to be affected by natural selection, rather than genetic drift.
      Therefore, even a small number of mutations within important regulatory sequences
      can provide evolutionarily significant variation and have an impact on
      environmental adaptation.

PMID- 11250553
TI  - Novel wax esters and hydrocarbons in the cuticular surface lipids of the red
      harvester ant, Pogonomyrmex barbatus.
AB  - The cuticular surface lipids of the red harvester ant, Pogonomyrmex barbatus,
      were found to contain minor amounts of novel wax esters, in addition to the major
      components, hydrocarbons. The wax esters ranged in carbon number from C19 to C31
      and consisted of esters of both odd- and even-numbered alcohols and acids. Each
      wax ester with a given carbon number eluted at several different retention times
      indicating possible methyl branching in either the fatty acid or alcohol moiety,
      or in both moieties. Each eluting peak of wax esters consisted of a mixture of
      wax esters of the same carbon number in which the fatty acid moiety ranged from
      C8 to C18, and the alcohol moiety ranged from C8 to C17. Some wax esters were
      largely found on the head indicating they may be of a glandular origin. The
      hydrocarbons consisted of: n-alkanes, C23 to C33; odd-numbered n-alkenes, C27 to
      C35; and the major components, methyl-branched alkanes, C26 to over C49. Notable
      components of the methyl-branched alkanes were 2-methyltriacontane, and the novel
      trimethylalkanes with a single methylene between the first and second branch
      points, 13,15,19-trimethylhentriacontane and 13,15,21-trimethyltritriacontane.

PMID- 11250555
TI  - A TiP(2)O(7) superstructure.
AB  - A room-temperature structural model of titanium pyrophosphate, TiP(2)O(7), has
      been determined from synchrotron X-ray data. The structure consists of TiO(6)
      octahedra and PO(4) tetrahedra sharing corners in a three-dimensional network.
      The PO(4) tetrahedra form P(2)O(7) groups connecting the TiO(6) octahedra. The 3
      x 3 x 3 superstructure differs substantially from the parent AB(2)O(7) structure.
      The P--O--P bonding angles of the pyrophosphate group are between 141.21 (12) and
      144.51 (13) degrees for those groups not located on the threefold axis. The
      individual TiO(6) octahedra and PO(4) tetrahedra are somewhat distorted.

PMID- 11250556
TI  - Li(2)Sn(OH)(6).
AB  - Hydrothermally prepared dilithium tin hexahydroxide crystallizes in the
      monoclinic system (space group P2(1)/n), with the Sn atom at a site with -1
      symmetry and all other atoms in general positions. The Sn coordination polyhedron
      is made up of six hydroxide groups. The Li atom is tetrahedrally coordinated by
      oxygen, with the tetrahedra sharing two corners and one edge with the adjacent Sn
      octahedra. Hydrogen bonds between the OH groups provide additional bonds in the
      framework.

PMID- 11250557
TI  - Hexagonal YMnO(3).
AB  - The crystal structure of hexagonal yttrium trioxomanganate has been determined at
      room temperature and at 180 K. It is isomorphous with LuMnO(3). The Mn
      displacement vector has a frustrated component in the ab plane and a
      ferroelectric part along the c axis. The net ferroelectricity is zero due to
      inversion twinning, with 1:1 twin fractions.

PMID- 11250558
TI  - Bis(tetrahydrofuran-kappa O)(meso-5,10,15,20-tetraisopropylporphyrinato
      kappa(4)N)iron(III) perchlorate.
AB  - The title complex, [Fe(C(32)H(36)N(4))(C(4)H(8)O)(2)]ClO(4), shows an S(4)
      ruffled porphyrin ring, where the maximum deviation of the meso-carbon from the
      least-squares plane of the [Fe(C(20)N(4))] core is as high as 0.675 (9) A. This
      is the highest class of deviation among S(4)-ruffled iron(III) porphyrin
      complexes. The average Fe-N(p) bond distance is 1.967 (12) A (N(p) denotes an N
      atom of the equatorial ligand).

PMID- 11250559
TI  - [eta(2)-(E)-But-2-enedinitrile](N,N'-di-phenyl-1,7,7-trimethylbicyclo[2.2.1]
      heptane-2,3-diimine-N,N')-palladium(0).
AB  - The zero-valent palladium in [Pd(C(4)H(2)N(2))(C(22)H(24)N(2))] is coordinated to
      two imine N atoms of a derivatized camphor ligand, and to the olefinic C atoms of
      a pi-bonded fumaronitrile group. The N--Pd--N bite angle of 77.31 (9) degrees is
      similar to angles observed in other zero-valent palladium diiminoalkene species.
      The asymmetry of the camphor moiety leads to two different orientations of the N
      aryl groups relative to the PdN(2) plane [C==N--C--C torsion angles of 102.4 (4)
      and 39.4 (4) degrees ].

PMID- 11250560
TI  - [Ethylene-1,2-bis(diphenylphosphine)-P,P']dinitratoplatinum(II) and cis
      bis[(diphenylphosphinomethyl)-diphenylphosphine oxide-O,P]-platinum (II)
      dinitrate dihydrate.
AB  - In [Pt(dppe)(NO(3))(2)], where dppe is ethylene-1,2-bis(diphenylphosphine)
      (C(26)H(24)P(2)), the Pt atom is coordinated by the two P atoms and by two O
      atoms of the two nitrate ions. The molecule has a distorted square-planar
      geometry, with one of the nitrate groups directed on each side of the plane. The
      cation in cis-[Pt(dppmO-O,P)(2)](NO(3))(2) x 2H(2)O, where dppmO is
      bis(diphenylphosphinomethyl)diphenylphosphine oxide (C(25)H(22)OP(2)), comprises
      two five-membered chelate rings, each dppmO ligand being coordinated to platinum
      through one P atom and the O atom. The larger P--Pt--P angle of 102.25 (4)
      degrees is due to steric interactions between the two phenyl groups on each P
      atom.

PMID- 11250561
TI  - Actinide interactions with microbial chelators: the dioxobis[pyridine-2,6
      bis(monothiocarboxylato)]uranium(VI) ion.
AB  - The title complex, bis(tetraphenylphosphonium) dioxobis(pyridine-2,6
      dicarbothioato-O,N,O')uranium(VI), (C(24)H(20)P)(2)[UO(2)(C(7)H(3)NO(2)S(2))(2)],
      was prepared by reacting two equivalents of pyridine-2,6-bis(monothiocarboxylate)
      (pdtc) with uranyl nitrate. The geometry of the eight-coordinate U atom is
      hexagonal bipyramidal, with the uranyl O atoms in apical positions. This is the
      first reported complex in which this ligand binds a metal through the O and not
      the S atoms. Principal bond lengths include uranyl lengths of 1.774 (2) A, U--O
      distances of 2.434 (2) and 2.447 (3) A, and two U--N distances of 2.647 (3) A.
      The anion lies on an inversion centre.

PMID- 11250562
TI  - Polymeric bis[bis(2,2'-bipyridine)-nickel(II)] hexavanadate(V).
AB  - The structure of the title compound, mu-hexavanadato(V)-bis[bis(2,2'
      bipyridine)nickel(II)], [(Ni(C(10)H(8)N(2))(2))(2)(V(6)O(17))], is composed of
      vanadium oxide layers intercalated by complex [Ni(bipy)(2)](2+) cations (bipy is
      2,2'-bipyridine). The structure is isomorphous with that reported recently for
      [Zn(bipy)(2)](2)[V(6)O(17)] [Zhang, DeBord, O'Connor, Haushalter, Clearfield &
      Zubieta (1996). Angew. Chem. Int. Ed. Engl. 35, 989--991]. The vanadium oxide
      layers are built up solely from VO(4) tetrahedra by corner sharing and clearly
      exhibit a sinusoidal ruffling. Two O atoms from a single vanadium oxide layer are
      coordinated to each Ni atom of the complex cations in a cis fashion, with Ni--O
      distances of 2.027 (3) and 2.087 (3) A, thus maintaining the two-dimensional
      structure.

PMID- 11250563
TI  - A decanuclear oxomolybdenum(V,VI) cluster with 4-isopropylpyridine.
AB  - The title centrosymmetric cluster octakis(4-isopropylpyridine-N)-di-mu(4)-oxo
      hexa-mu(3)-oxo-octa-mu(2)-oxo-decaoxooctamolybdenum(V)dimolybdenum(VI),
      [Mo(10)O(26)(C(8)H(11)N)(8)], consists of ten Mo atoms connected together by
      bridging oxo groups. Pentavalent Mo atoms are linked into four [Mo(2)](V) pairs
      by metal--metal single bonds with lengths of 2.5637 (6) and 2.6132 (6) A.

PMID- 11250564
TI  - (Acridine-N)trichlorogold(III).
AB  - The title compound, [AuCl(3)(C(13)H(9)N)], is the first complex of gold and
      acridine to be reported. The coordination sphere of the Au atom is square planar.
      The crystal structure is built up of neutral complex molecules linked into chains
      by means of attractive pi--pi interactions between the parallel acridine ligands.

PMID- 11250565
TI  - Sodium hydrogen bis(phenoxyacetate).
AB  - In the title compound, Na(+) x H(+) x [2C(8)H(7)O(3)](-), the anion contains a
      short Speakman-type hydrogen bond [O...O = 2.413 (2) A]. The anions and the Na
      atoms lie across twofold axes.

PMID- 11250567
TI  - Polymeric[mu(3)-(N-phosphonomethyl)-glycinato]tris(tri-n-butyltin).
AB  - N-(Phosphonomethyl)glycine, glyphosate, reacts with bis(tributyltin) oxide to
      form a ligand--tin (1:3) complex in which all five O atoms are coordinated to
      tin. The complex, [Sn(3)(C(4)H(9))(9)(C(3)H(5)NO(5)P)], is polymeric, with the
      glyphosate and two tributyltin groups forming a two-dimensional network and with
      the third Sn atom alternately above and below the plane of the net. The Sn atoms
      in the network have a trigonal-bipyramidal coordination, with O atoms in the
      axial positions and C atoms in the equatorial positions; the pendant tributyltin
      group is tetrahedrally coordinated to one O atom and to three butyl groups. Sn--O
      distances vary from 2.030 (3) to 2.408 (3) A. The Sn--O distances for O atoms
      trans to carboxylate groups are shorter than those trans to phosphonate groups
      and d(Sn--O) decreases with increasing d(C/P--O) (Delta(Sn--O) approximately -4.6
      Delta(C/P--O)). The amino N atom in the ligand is neither protonated nor involved
      in coordination to the Sn atoms.

PMID- 11250568
TI  - Two polymorphs of aqua[N,N'-ethylenebis(salicylideneaminato-N,O)]-oxovanadium(V)
      nitrate.
AB  - The title compound, aqua[bis(salicylidene)ethylenediaminato
      O,N,N',O']oxovanadium(V) nitrate, [VO(C(16)H(14)N(2)O(2))(H(2)O)]NO(3),
      crystallizes as two polymorphs in the triclinic and monoclinic crystal systems.
      In both, the V atom has a distorted octahedral coordination geometry with a long
      V--O(water) bond trans to V==O. The coordinated water molecules are hydrogen
      bonded to the nitrate ions so that pairs of cations are linked to give neutral
      centrosymmetric dimers. The V==O and V--O(water) distances are 1.598 (2) and
      2.257 (2) A, respectively, in the triclinic form, and 1.588 (3) and 2.230 (3) A,
      respectively, in the monoclinic form. In the triclinic form, the dimers pack so
      that the salen [bis(salicylidene)ethylenediaminate] ligands are parallel to each
      other, whereas in the monoclinic form, which is the denser, there is a herring
      bone arrangement.

PMID- 11250566
TI  - [5,10,15,20-Tetrakis(2-thienyl)-porphyrinato]zinc(II).
AB  - In the title complex, [Zn(C(36)H(20)N(4)S(4))], the Zn(II) ion occupies a special
      position on an inversion centre with four-coordinate geometry. The porphyrin ring
      shows a wave-like conformation, with the closest interporphyrin plane separation
      being 3.60 (6) A. The two disordered thienyl groups are inclined with respect to
      the porphyrin plane at angles of 70 (4) and 67 (2) degrees.

PMID- 11250569
TI  - Poly[copper(II)-mu-pyrazine-mu(3)-squarato].
AB  - In the structure of the title compound, [Cu(C(4)O(4))(C(4)H(4)N(2))](n), each
      copper cation is surrounded by three squarate (3,4-dihydroxy-3-cyclobutene-1,2
      dioate) anions and two pyrazine ligands, all of which are located in special
      positions. The copper cation and all atoms of the squarate anion are located on a
      mirror plane, whereas the pyrazine ligand is located around a mirror plane which
      is perpendicular to the ring plane. The cations are connected via the squarate
      anions and the pyrazine ligands, forming sheets parallel to (001).

PMID- 11250570
TI  - Doxylaminium tetrachlorocuprate(II).
AB  - The structure of the title compound, 2-[1-(dimethylammonioethoxy)-1
      phenylethyl]pyridinium tetrachlorocuprate(II), (C(17)H(24)N(2)O)[CuCl(4)],
      contains dihydro cations of doxylamine hydrogen bonded to two Cl atoms in two
      different [CuCl(4)](2-) anions, with Cl...N distances of 3.101 (9) and 3.253 (10)
      A. The ethereal O atom is involved in intramolecular hydrogen bonds, with O.N
      distances of 2.517 (11) and 2.757 (12) A. The molecular dimensions in the cation
      are as expected and the [CuCl(4)](2-) anion has a flattened tetrahedral geometry.

PMID- 11250571
TI  - Enantiomeric disorder in racemic cis-dichlorobis(pentane-2,4
      dionato)titanium(IV).
AB  - The title compound, [Ti(C(5)H(7)O(2))(2)Cl(2)], adopts the cis configuration. The
      racemic compound crystallizes in space group P1 and each molecular site has 0.50
      occupancy by each of the two enantiomorphs. The enantiomeric disorder is
      correlated in two dimensions.

PMID- 11250572
TI  - A ferric-cyanide-bridged one-dimensional dirhodium complex with (18-crown
      6)potassium cations.
AB  - The crystal structure of the title compound, catena-poly[bis[aqua(18-crown
      6)potassium] diaqua(18-crown-6)potassium [[tetra-mu-benzoato-2:3 kappa(8)O:O'-mu
      cyano-1:2 kappa(2)C:N-tetracyano-1 kappa C-irondirhodium(Rh-Rh)]-mu-cyano-1 kappa
      C:3' kappa N] octahydrate], [K(18-crown-6)(H(2)O)](2)[K(18-crown
      6)(H(2)O)(2)][FeRh(2)(C(7)H(5)O(2))(4)(CN)(6)] x 8H(2)O, where (18-crown-6) is
      1,4,7,10,13,16-hexaoxacyclooctadecane (C(12)H(24)O(6)), has been determined.
      Ferric cyanides connect the dirhodium units to form a one-dimensional chain
      compound. [K(18-crown-6-ether)(H(2)O)(2)] cations (with inversion symmetry) and
      [K(18-crown-6-ether)(H(2)O)] cations (in general positions) are located between
      the chains.

PMID- 11250573
TI  - A nido-6-manganadecaborane salt.
AB  - A new manganadecaborane has been isolated as a previously unsuspected product
      from the reaction of [Mn(CO)(5)Br] with K[B(9)H(14)]. The anion of
      tetrabutylammonium 5-bromo-6,6,6-tricarbonyl-6-manganadodecahydrodecaborate(1-),
      (C(16)H(36)N)[Mn(B(9)H(12)Br)(CO)(3)], has a nido cage structure. The Mn atom is
      bonded through three B--Mn bonds of similar length [2.221 (4), 2.224 (3) and
      2.236 (3) A] and two bridging H atoms. The position of the bromo substituent
      breaks the twofold symmetry of the cage found in simple analogues, and this is
      reflected in the B--B bond parameters.

PMID- 11250575
TI  - Bis[(mu-acetato[mu-bis(salicylidene-1,3-propanediaminoato]zinc(II)]zinc(II).
AB  - In the title linear trinuclear compound,
      [Zn[Zn(CH(3)COO)(C(17)H(16)N(2)O(2))](2)], the central Zn(2+) ion, which is
      located on an inversion centre, has a distorted octahedral coordination involving
      four bridging O atoms from two N,N'-bis(salicylidene)-1,3-propanediaminate
      ligands in the equatorial plane and one O atom from each bridging acetate group
      in the axial positions. The coordination around the terminal Zn(2+) ion is
      irregular square pyramidal, with two O and two N atoms of the ligand in the basal
      plane and one O atom from an acetate group in the apical position. The acetate
      bridges linking the central and terminal Zn(2+) ions are mutually trans. The
      Zn.Zn distance is 3.0520 (8) A. The relationship of this structure to that of
      [Zn[Cu(CH(3)COO)(C(17)H(16)N(2)O(2))](2)] is discussed.

PMID- 11250574
TI  - trans-Bis(ethanolamine-N,O)bis(saccharinato-N)copper(II).
AB  - In the title complex, [Cu(C(7)H(4)NO(3)S)(2)(C(2)H(7)NO)(2)], the Cu(II) centre
      lies on an inversion centre and exhibits octahedral coordination, with the two
      ethanolamine (Hea) and two saccharinate [sac; anionic 1,2-benzisothiazol-3(2H)
      one 1,1-dioxide] ligands in a trans configuration. The bidentate Hea ligands
      bridge axial and equatorial positions and the sac anions occupy equatorial sites
      around the distorted octahedral copper(II) centre [Cu--O = 2.3263 (16), Cu-
      N(Hea) = 1.9923 (16) and Cu--N(sac) = 2.1776 (16) A].

PMID- 11250576
TI  - (4'-Chloro-2,2':6',2"-terpyridine-N,N',N")(diethylphosphinothioato-S)platinum(II)
      tetraphenylborate.
AB  - The title compound, [Pt(C(4)H(10)O(3)PS)(C(15)H(10)ClN(3))](C(24)H(20)B), has a
      distorted square-planar coordination geometry at the platinum(II) centre, due to
      the constraints of the tridentate terpyridine ligand. The Pt(II)-bound
      diethylphosphinothioate ligand takes up a conformation to avoid non-bonding
      contacts with atoms H6 and H6".

PMID- 11250577
TI  - Fluoro derivatives of bis(salicylideneaminato-N,O)copper(II) and 
      oxovanadium(IV).
AB  - The structures of five complexes of fluorine-containing bidentate
      salicylideneamine Schiff base ligands are reported. These are the bis-ligand
      copper(II) complexes of the Schiff bases derived from salicylaldehyde and 4
      fluoro-, [Cu(C(13)H(9)FNO)(2)], 3-fluoro-4-methyl-, [Cu(C(14)H(11)FNO)(2)], 3,5
      bis(trifluoromethyl)-, [Cu(C(15)H(8)F(6)NO)(2)], and 4-trifluoromethoxyanilines,
      [Cu(C(14)H(9)F(3)NO(2))(2)], and the bis-ligand oxovanadium(IV) complex of the
      Schiff base derived from salicylaldehyde and 4-trifluoromethoxyaniline,
      [VO(C(14)H(9)F(3)NO(2))(2)]. Three of the copper complexes have square-planar
      coordination at the metal, imposed by the virtue of symmetry, but the immediate
      coordination environment of the copper in the 3,5-bis(trifluoromethyl) complex is
      intermediate between square planar and tetrahedral. The coordination environment
      at the metal of the vanadium complex can be described as distorted square
      pyramidal.

PMID- 11250578
TI  - 5,12-Dimethyl-3,10-diphenyl-1,3,4,8,10,11
      hexaazatetracyclo[6.6.1.0(2,6).0(9,13)]pentadeca-2(6),4,9,(13),11-tetraene,a new
      Troger's base analogue.
AB  - The synthesis of the title Troger's base analogue, C(23)H(22)N(6), was undertaken
      in order to study the influence of a methyl substituent on the structure. Minor
      differences were found in the bond lengths of the title structure in comparison
      with the values for free pyrazole and for the first pyrazolic Troger's base
      reported in the literature. There are two molecules of opposite chirality in the
      asymmetric unit and the packing in the lattice is characterized by a non
      crystallographic n-glide plane relating these molecules.

PMID- 11250579
TI  - A hydrogen-bonded 'trimer' of two symmetric dipyridones.
AB  - The isomers 3,3'-(1,2-ethynediyl)bis(2-pyridone), (I), and 6,6'-(1,2
      ethynediyl)bis(2-pyridone), (II), were designed to form a hydrogen-bonded pair
      through alignment of their complementary cyclic lactam moieties. Instead, an
      equimolar mixture of (I) and (II) dissolved in methanol produced crystals of 3,3'
      (1,2-ethynediyl)bis(2-pyridone)-6,6'-(1,2-ethynediyl)bis(2-pyridone)-methanol
      (1/2/2), 0.5C(12)H(8)N(2)O(2) x C(12)H(8)N(2)O(2) x CH(4)O, in which one molecule
      of (I), situated at a center of symmetry, is hydrogen bonded to two molecules of
      (II) and to two molecules of methanol.

PMID- 11250581
TI  - Bis[2,2'-ethylenedioxydibenzaldehyde bis(thiocarbohydrazide)] tris(pyridine)
      solvate.
AB  - The title compound, a novel 30-membered 2:2 macrocyclic thiocarbohydrazone,
      C(34)H(32)N(8)O(4)S(2) x 3C(5)H(5)N, has been prepared and crystallographically
      characterized. The molecule of the compound is twisted. One dioxabutane group is
      boat-like in shape, whereas the other is highly disordered. The crystal structure
      is stabilized by inter- and intramolecular hydrogen bonds.

PMID- 11250580
TI  - Two natural products from the algae Laurencia scoparia.
AB  - The structures and absolute stereochemistries of two chamigrene-type metabolites
      (spiro[5.5]undecane derivatives) isolated from the red algae Laurencia scoparia
      are described. One, a non-sesquiterpene named mailione (8-bromo-9-hydroxy-7,7
      dimethyl-11-methylenespiro[5.5]undec-1-en-3-one), C(14)H(19)BrO(2), was detected
      previously in Laurencia cartilaginea, while the other, the sesquiterpene
      isorigidol (8-bromo-3,7,7-trimethyl-11-methylenespiro[5.5]-undec-1-ene-3,9-diol),
      C(15)H(23)BrO(2), is a new isomer of rigidol, first isolated from Laurencia
      rigida. The A rings of these spirocyclic compounds show the same carbon skeleton.
      However, the relative stereochemistry of the 8-Br and 9-OH substituents is
      different. While mailione displays the usual syn (or cis) relative
      stereochemistry of the bromohydroxy vicinal group, isorigidol shows an anti (or
      trans) arrangement. The 8-Br and 9-OH groups are both in equatorial positions in
      isorigidol, while the 9-OH group is axial in mailione, as in most chamigrenes.
      The absolute configurations of the chiral centers were determined as 6S, 8S and
      9R in mailione, and 3R, 6S, 8S and 9S in isorigidol.

PMID- 11250582
TI  - Bis(dicyclohexylammonium 3-thienylacetate).
AB  - The triclinic cell of the title compound contains 2C(12)H(24)N(+) x
      2C(6)H(5)O(2)S(-) ion pairs that are linked by four hydrogen bonds [N...O = 2.728
      (3) and 2.758 (3) A] across a centre of inversion.

PMID- 11250583
TI  - 6,7-Bis(bromomethyl)-2,11,18,21,24-pentaoxatetracyclo.
AB  - The 17-crown-5 unit, C(26)H(26)Br(2)O(5), consisting of a 1,2-bis(bromomethyl)
      group, three benzo groups and diethylene glycol, was prepared from the reaction
      of 1,2,4,5-tetrakis(bromomethyl)benzene and bis-phenol in the presence of sodium
      hydride as a base. This molecule seems to offer an internal cavity for the
      formation of a host--guest complex.

PMID- 11250584
TI  - 4-(Phenyldiazenyl)naphthalen-1-amine and its hydrochloride.
AB  - The crystal structures of 4-(phenyldiazenyl)naphthalen-1-amine, C(16)H(13)N(3),
      (I), and its hydrochloride, (4-aminonaphthalen-1-yl)phenyldiazenium chloride,
      C(16)H(14)N(3)(+) x Cl(-), (II), have been determined from X-ray single-crystal
      and powder data, respectively. The effect of the crystal environment on the
      molecular electronic structure was analysed on the AM1 level. One of the two
      symmetry-independent molecules in (I) is involved in intermolecular hydrogen
      bonding, so that its dipole moment is twice as large as that of the other
      molecule. The cations in (II) form stacks along [100], with the Cl(-) anions
      forming hydrogen bonds to all three H atoms attached to N atoms.

PMID- 11250585
TI  - Three 1,6-anhydro-beta-D-glycopyranose derivatives.
AB  - Two of the title compounds, 1,6-anhydro-2,3-O-(S)-benzylidene-beta-D
      mannopyranose, C(13)H(14)O(5), (I), and 1,6-anhydro-4-O-benzyl-beta-D
      mannopyranose, C(13)H(16)O(5), (II), are derived from beta-D-mannopyranose, while
      the third, 1,6-anhydro-3,4-O-(S)-benzylidene-beta-D-galactopyranose,
      C(13)H(14)O(5), (III), is derived from beta-D-galactopyranose. In the crystal
      packing, each hydroxyl group is involved in O-H.O hydrogen bonds, where the
      acceptor group is the other hydroxyl group in (II), or the endocyclic O atoms of
      the dioxolane [in (I)], anhydro [in (II)] or pyranose [in (III)] rings.
      Differences in the crystal packing arise from the contrasting O--H...O hydrogen
      bonding environments.

PMID- 11250586
TI  - The 1:1 adduct of 2,5-dihydroxy-1,4-benzoquinone with 4,4'-bipyridine.
AB  - 2,5-Dihydroxy-1,4-benzoquinone (DHBQ) and 4,4'-bipyridine (BPY) crystallize in a
      1:1 ratio as a neutral molecular adduct, C(6)H(4)O(4).C(10)H(8)N(2), in space
      group C2/c, with half of each molecule in the asymmetric unit. The molecules are
      linked by a strong O--H...N hydrogen bond [O...N 2.6323 (15) A] and a weak C-
      H...O hydrogen bond [C...O 3.2082 (17) A] to form infinite stacks of parallel one
      dimensional hydrogen-bonded ribbons. The two rings of the bipyridine are twisted
      at 28.3 degrees with respect to each other, and the benzoquinone ring is inclined
      at an angle of 18.3 degrees with respect to the plane of the neighbouring
      pyridine ring. The 4,4'-bipyridine molecule lies on a twofold axis and the
      benzoquinone molecule lies across an inversion centre.

PMID- 11250587
TI  - 1-Nitroindoline.
AB  - In the title compound, C(8)H(8)N(2)O(2), the nitramino group is planar and only
      slightly twisted with respect to the indoline rings. The bridgehead N--C bond is
      slightly shorter than in typical secondary aromatic nitramines. The N--N bond has
      some double-bond character. The molecules are connected by weak C--H...O hydrogen
      bonds, forming chains parallel to the z direction.

PMID- 11250588
TI  - Benzyltrimethylammonium hydroxide trihydrate containing hydroxide--water layers.
AB  - In the title compound, C(10)H(16)N(+) x OH(-) x 3H(2)O, two-dimensional bilayer
      like arrays of organic cations and corrugated anionic hydroxide-water layers are
      stacked alternately along the c axis. All hydroxide and water H atoms are in
      ordered positions, giving rise to a network of hydrogen bonds [O...O 2.639 (2)-
      2.927 (2) A for water donors and O...O 3.323 (2) A for hydroxide donors] with
      four- and six-membered rings.

PMID- 11250589
TI  - Methyl 2,3,6-tri-O-benzoyl-4-deoxy-4-methoxyamino-alpha-D-glucopyranoside.
AB  - The crystalline-state conformation of the title compound, C(29)H(29)NO(9), has
      been established unequivocally. The R absolute configuration is observed at the 4
      methoxyamino moiety and the pyranose ring adopts essentially a perfect (4)C(1)
      chair. The torsion angle of the exocyclic hydroxymethyl group is shown to be
      gauche--gauche with respect to O1 and C4, respectively. The conformation along
      the methoxyamino bond is consistent with that observed for calicheamicin
      gamma(1)(I).

PMID- 11250590
TI  - Hydrogen-bonded sheets in the 1:1 salt of tet-b and trimesic acid.
AB  - Tet-b (racemic 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane,
      C(16)H(36)N(4)) and trimesic acid (1,3,5-benzenetricarboxylic acid, C(9)H(6)O(6))
      form a salt partially solvated by both water and methanol, i.e. 5,5,7,12,12,14
      hexamethyl-1,4,8,11-tetraazacyclotetradecane-1,3,5-benzenetricarboxylic acid-
      methanol--water (1/1/0.78/1.12), C(16)H(38)N(4)(2+) x C(9)H(4)O(6)(2-) x
      0.78CH(4)O x 1.12H(2)O. The anions are linked by O--H...O hydrogen bonds [O...O
      2.442 (4) and 2.458 (4) A; O--H...O 170 and 171 degrees ] into zigzag chains;
      orientationally disordered cations are linked to the anion chains by means of N-
      H...O hydrogen bonds [major orientation: N...O 2.695 (3)--3.071 (4) A, N--H...O
      148--179 degrees; minor orientation: N...O 2.75 (2)--3.34 (2) A, N--H...O 147-
      170 degrees ] and link the chains into sheets. The solvent molecules are all
      disordered, but appear to play no significant structural role apart from space
      filling.

PMID- 11250591
TI  - Hydrogen bonding in C-methylated nitroanilines: the three-dimensional framework
      structure of 2-methyl-4-nitroaniline.
AB  - Molecules of 2-methyl-4-nitroaniline, C(7)H(8)N(2)O(2), act as double donors and
      as double acceptors of N--H...O hydrogen bonds [N...O 3.117 (3) and 3.239 (3) A;
      N--H...O 169 and 136 degrees ]. The molecules are thereby linked into a three
      dimensional framework.

PMID- 11250592
TI  - 1-(Dibromomethyl)-4-methoxy-2-methylbenzene.
AB  - The title compound, C(9)H(10)Br(2)O, is a major product of the radical
      bromination of 4-methoxy-1,2-dimethylbenzene. Each Br atom is involved in a close
      contact with the O atom of a neighbouring molecule, forming a geometry that is
      suggestive of weak intermolecular O--> Br charge-transfer interactions.

PMID- 11250593
TI  - 5-Benzyl-5-phenyl[1,3]dithiolo[4,5-d]-[1,3]dithiole-2-thione.
AB  - In the title compound, C(17)H(12)S(5), the dithiole ring bearing the aryl
      substituents assumes an envelope conformation with the maximum deviation from
      planarity being -0.053 A. The phenyl and benzyl rings are twisted by 33.0 (1) and
      31.1 (1) degrees, respectively, out of the dithiole plane. The crystal packing is
      governed by short S...S interactions, with the shortest being 3.550 (2) A.

PMID- 11250594
TI  - Tritosylate of diethanolamine.
AB  - The crystal structure of the tritosylated diethanolamine N,N-bis(tosyloxyethyl)-p
      toluenesulfonamide, C(25)H(29)NO(8)S(3), has been determined. The conformation of
      the molecule is such that the tosyl groups are as far apart as possible. The
      molecules are interconnected by C--H...O hydrogen bonds and form columns in the
      crystal structure.

PMID- 11250595
TI  - Tris(tert-butyl)phosphine selenide, the missing link in tris(tert-butyl)phosphine
      chalcogenide structures (t)Bu(3)P==X (X = O, S, Se, Te).
AB  - In tris(tert-butyl)phosphine selenide, C(12)H(27)PSe, all the methyl ligands are
      disordered over two sites in the ratio 70/30. The molecule displays
      crystallographic C(3) symmetry. The bond angles at the P atom are distorted
      tetrahedral [C--P--C 110.02 (5) degrees and Se==P--C 108.91 (5) degrees ]. The P-
      C and P==Se bond lengths are 1.908 (1) and 2.1326 (6) A, respectively. A
      comparison of the structural data of the complete series of tris(tert
      butyl)phosphine chalcogenides ((t)Bu(3)PO, (t)Bu(3)PS, (t)Bu(3)PSe and
      (t)Bu(3)PTe) with the corresponding data of other phosphine chalcogenides
      substituted by smaller organic groups shows the great influence of the bulky tert
      butyl ligands.

PMID- 11250596
TI  - (+/-)-1-Tetralone-3-carboxylic acid and (+/-)-1-tetralone-2-acetic acid: hydrogen
      bonding in two gamma-keto acids.
AB  - The crystal structure of (+/-)-4-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylic
      acid (C(11)H(10)O(3)) involves projection of the carboxyl group nearly orthogonal
      to the aromatic plane and hydrogen bonding of the acid groups by centrosymmetric
      pairing across the a edge and the center of the chosen cell [O...O = 2.705 (2)
      A]. Intermolecular C--H...O==C close contacts to translationally related
      molecules are found for both the ketone (2.55 A) and the acid (2.67 A). In (+/-)
      1-oxo-1,2,3,4-tetrahydronaphthalene-2-acetic acid (C(12)H(12)O(3)), the
      aggregation involves centrosymmetric carboxyl dimers mutually hydrogen bonded
      across the bc face and the a edge of the chosen cell [O...O = 2.674 (2) A]. A
      2.60 A close C--H...O==C contact is found to the carboxyl group of
      centrosymmetrically related molecule.

PMID- 11250597
TI  - [Epidemiology of cancer of the upper aerodigestive tract].

PMID- 11250598
TI  - [Epidermoid cancer of the oropharynx].

PMID- 11250599
TI  - [Carcinoma of the nasopharynx].

PMID- 11250600
TI  - [Cancer of the larynx and the hypopharynx: anatomy, anatomopathology, clinical
      signals, TNM, therapy].

PMID- 11250601
TI  - [Cancer of the oral cavity].

PMID- 11250602
TI  - [Surveillance of patients treated for a cervico-facial cancer].

PMID- 11250603
TI  - [Aromatase inhibitors].

PMID- 11250604
TI  - [Preclinical evaluation of aromatase inhibitors antitumor activity].
AB  - Aromatase is an enzymatic complex responsible for the conversion of androgens
      into estrogens; these hormones are important in development, reproduction, but
      also in the growth of estrogen-dependent cancer. This enzyme is present in 60-70%
      of the breast cancer. The aromatase inhibitors are important drugs in the breast
      cancer treatment of postmenopausal women. In order to study their in vivo
      activity, animal models have been developed, e.g. rat with tumour induced by 7,12
      dimethylbenz[a]anthracene, PMSG-primed immature rat or athymic nude mice with
      aromatase transfected MCF-7 xenograft. In this review, we were interested in
      preclinical results obtained with both classes: steroidal and nonsteroidal
      inhibitors. The former group, as substrate analogs formestane or exemestane, are
      irreversible, selective and long-lasting inhibitors of aromatase. The
      nonsteroidal molecules, such as letrozole or anastrozole, are reversible
      inhibitors with high affinity. Finally, knowledge of the enzyme active site, with
      molecular modeling and site-directed mutagenesis, could be useful to develop new
      inhibitor families, more specific and potent in vivo.

PMID- 11250605
TI  - [Aromatase inhibitors: pharmacological aspects].
AB  - Selective new aromatase inhibitors are a new class of agents that are of
      considerable interest in the treatment of hormone-dependent breast cancer in
      postmenopausal women. Aromatase is an enzymic complex that catalyses the
      conversion of the adrenal androgens androstenedione and testosterone to estrone.
      In postmenopausal women, the process of peripheral aromatisation accounts for the
      majority of circulating estrogens. The selective inhibition of estrogen
      production by aromatase inhibitors is an efficient strategy for breast cancer
      treatment. These compounds are classified as irreversible inhibitors of aromatase
      (type I), and comprise steroidal compounds. Reversible inhibitors of aromatase,
      which comprises non-steroidal compounds are type II aromatase inhibitors. Second
      and third generation aromatase inhibitors are considerably more potent and more
      specific in their ability to inhibit aromatase, as compared with first generation
      compounds (aminoglutethimide).

PMID- 11250606
TI  - [Aromatase inhibitors: a review of clinical trials].
AB  - To increase the therapeutic index of second line hormonal treatment of breast
      cancer, new aromatase inhibitors have been synthetized; they belong to two
      groups: type I (formestane and exemestane) are steroidal irreversible and
      specific inhibitors, type II (anastrozole, letrozole and vorozole) are non
      steroidal reversible inhibitors, interfering with the aromatase heme. Several
      phase II and III trials demonstrated that these drugs are, at least, as active as
      aminoglutethimid or progestins in second line treatment, and are less toxic.
      Recently, an identical activity have been observed for anastrozole and tamoxifen
      in first line. In metastatic and adjuvant settings, large trials are ongoing to
      clarify the exact value of these drugs.

PMID- 11250607
TI  - [Aromatase inhibitors: therapeutic outlook].
AB  - Hormone therapy of breast cancer has been dominated for a very long time by a
      single class of drugs, the antiestrogens, and especially tamoxifen. Tamoxifen has
      been the standard treatment in the adjuvant, neoadjuvant, and metastatic
      contexts. Ten years ago a new generation of aromatase inhibitors became available
      that was more selective than previous generations. They form two groups that are
      quite distinct from a pharmacological standpoint: type II non-steroid inhibitors
      and type I steroid inhibitors or rather steroid "aromatase inactivators".
      Aromatase inhibitors are prescribed to menopausal women. They are active in
      patients with tamoxifen-resistant metastatic cancer. They are a potential
      alternative to tamoxifen in first-line therapy of women with metastatic cancer.
      They have been proven useful as neoadjuvant therapy. They are under study in
      several trials in an adjuvant context. Many issues still remain outstanding.

PMID- 11250611
TI  - The care and management of pertussis in pediatric patients.

PMID- 11250612
TI  - The Royal Flying Doctor Service of Australia: the world's first air medical
      organization.

PMID- 11250613
TI  - What happens with failed blind nasal tracheal intubations?
AB  - INTRODUCTION: Flight nurses and paramedics may be called on to perform a blind
      nasal tracheal intubation (BNTI) as an airway management adjunct. A literature
      review found two publications addressing air medical BNTI failure rates. No
      studies examining demographic factors associated with BNTI failure rates nor
      published reports evaluating the failure rates of subsequent oral tracheal
      intubation (OTI) and cricothyroidotomy (cric) attempts after failed BNTI were
      found. This study was undertaken to identify factors associated with BNTI failure
      and determine the failure rates for OTI and cric performed by flight nurses and
      paramedics after failed BNTI. METHODS: All flight nurses' and paramedics' BNTI
      attempts and subsequent OTI and cric attempts after failed BNTI during 1999 were
      reviewed retrospectively. BNTI, OTI, and cric success versus failure groups
      subsequently were evaluated by student t-test and chi-squared analysis to
      determine if demographic differences for age, gender, type of illness (medical,
      cardiac, or trauma), in-hospital versus scene, nurse versus paramedic, and rotor-
      versus fixed-wing transport could be found. A P value < 0.05 was considered
      statistically significant. RESULTS: Thirty-six BNTIs were attempted by flight
      nurses (N = 34) and paramedics (N = 2). Twenty-one BNTIs were attempted at the
      scene of injury, whereas 15 were attempted in the hospital setting. Eleven of 36
      (31%) patient attempts were unsuccessful, and all of these patients received
      subsequent OTI attempts. Of the 11 OTI patient attempts, two were unsuccessful
      (18%) and subsequently required cricothyroidotomy. Both attempted patient
      cricothyroidotomies were successful. Failed versus successful BNTIs were analyzed
      for demographic differences. Our study found that the BNTI failure (10/21, 48%)
      was significantly more likely to occur in younger (P < 0.001) trauma (P < 0.01)
      patients transported from the scene of injury (P < 0.05) by rotor-wing (P < 0.05)
      than in the hospital (1/15, 7%) setting. Unlike BNTIs, no significant demographic
      differences were observed between the failed (2/11, 18%) versus successful (9/11,
      82%) OTI after a failed nasal tracheal intubation. CONCLUSION: Flight nurse and
      flight paramedic teams show a rather low BNTI failure (7%) rate within the
      confines of the hospital setting but a significantly higher failure rate (48%)
      when this procedure is performed at the scene of an injury. Although not measured
      in this study, this difference may represent fewer insertion attempts, less time
      spent performing BNTI because of the need to rapidly transport trauma patients to
      appropriate treatment centers, or variation in technique because of the concern
      for cervical spine injury. Further studies are required to elucidate why
      differences in scene versus in-hospital BNTI success rates are occurring.

PMID- 11250615
TI  - Comparison of the laryngeal mask airway versus blind endotracheal intubation in
      the simulated entrapped patient: a preliminary study.

PMID- 11250614
TI  - A national survey of the air medical transport of high-risk obstetric patients.
AB  - INTRODUCTION: Air medical transport of high-risk obstetric (HROB) patients can be
      accomplished and advantageous for neonate survival and maternal morbidity. A
      survey of U.S. helicopter air medical programs was conducted to determine the
      frequency and current practices of HROB transport. METHODS: Each program was
      contacted by telephone, and air medical personnel were asked to answer 12
      questions based on personal experience and statistics compiled by their programs.
      RESULTS: Of the 203 programs surveyed, 133 (66%) provided responses. The mean
      number of HROB transports was 45.6 per year (4.6% of the mean 995 total
      transports). Although 83% of the responding programs used the standard flight
      crew during the HROB transport, only 52% required crew members to maintain
      neonatal resuscitation certification. Only 56% of the aircraft allow pelvic
      access in the normal patient configuration. While only 22% of programs have
      specific HROB launch (dispatch) protocols, 50% reported having obstetricians
      involved in dispatching flights, and 84% carry tocolytic agents in their drug
      kit. The greatest concerns included in-flight delivery (60%), inadequate fetal
      monitoring (6%), and inexperience (5%). CONCLUSION: While HROBs account for 5% of
      air medical flights, many programs appear to be poorly prepared for these
      patients.

PMID- 11250617
TI  - Treatment of the pediatric snakebite victim.

PMID- 11250618
TI  - The role of air medical services in envenomation: An international perspective.

PMID- 11250620
TI  - Fragmentation hinders development of diagnostic disciplines.

PMID- 11250621
TI  - Diabetes mellitus: Relevance to dental treatment.

PMID- 11250622
TI  - Vascular malformations in a 3(1/2)-year-old child.

PMID- 11250623
TI  - Mandibular range of motion after bilateral sagittal split ramus osteotomy with
      wire osteosynthesis or rigid fixation.
AB  - OBJECTIVES: An analysis was conducted to compare mandibular range of motion among
      Class II patients treated with wire osteosynthesis or rigid internal fixation
      after surgical mandibular advancement. STUDY DESIGN: Patients randomly received
      wire osteosynthesis and 8 weeks of maxillomandibular fixation (n = 49) or rigid
      internal fixation (n = 78). Mandibular range of motion was measured 2 weeks
      before surgery and 8 weeks, 6 months, and 1, 2, and 5 years after surgery.
      RESULTS: Both groups showed decreased mobility in all movement dimensions that
      progressively recovered to near presurgical levels over the 5-year follow-up
      period. The difference in range of motion between treatment groups was not
      statistically significant. Changes in proximal and distal segment position could
      not explain decreased mobility. CONCLUSIONS: Similar decreases in mandibular
      mobility occurred with wire and rigid fixation of a bilateral sagittal split
      ramus osteotomy after surgery. Long-term changes were statistically, but not
      clinically, significant.

PMID- 11250625
TI  - Frequency of chlamydial antibodies in patients with internal derangement of the
      temporomandibular joint.
AB  - PURPOSE: This study investigates whether an increased frequency of serum
      antibodies to Chlamydia trachomatis is found in patients with internal
      derangement of the temporomandibular joint (TMJ). PATIENTS AND METHODS: An
      indirect immunofluorescence antibody assay for the detection of serum
      immunoglobulin G antibodies for C trachomatis was used for most patients. Forty
      one female patients were evaluated. RESULTS: Three of 41 patients (7%) had serum
      antibody titers that were considered positive for active C trachomatis infection.
      Eleven patients (27%) were considered to have had a past infection based on the
      immunoglobulin G or immunoglobulin A titer results. Using the binomial test, we
      found that the probability of observing 14 positive results (34%) was significant
      (P < .0001). CONCLUSIONS: An increase in the frequency of serum antibodies to C
      trachomatis was found in patients with internal derangement of the TMJ. Serologic
      testing for antibodies to bacteria associated with reactive arthritis might be
      useful in the evaluation of patients with internal derangement of the TMJ.

PMID- 11250624
TI  - Use of membrane and bone grafts in the reconstruction of orbital fractures.
AB  - OBJECTIVE: To present and analyze the clinical results derived from the use of
      different grafts for the reconstruction of orbital defects during a 10-year
      period. STUDY DESIGN: Fifty-five fracture cases with orbital bony defect,
      requiring a graft, are presented. The surgical treatment includes the
      reconstruction of the fracture (osteosynthesis) and the repair of the remaining
      bone defect by graft, with the type of graft dependent on the size of the defect.
      For minor defects membranes were used (lyophilized dura or alloplastic dura
      mater), whereas major defects were repaired with bone grafts (autografts,
      heterografts, or bone substitute material). All patients have been regularly
      evaluated for at least one year postoperatively. RESULTS: All grafts were well
      tolerated by the patients. Diplopia subsided in all but 5 cases, motility
      disturbance was fully repaired in all but 3 cases. Esthetics were improved in
      cases with severe bone defect. CONCLUSION: The wide variety of grafts available
      allows successful reconstruction of all types of orbital bony defects. The
      clinician should be able to use different types of grafts depending on the type
      and size of the defect.

PMID- 11250626
TI  - Prognostic value of response to preoperative chemoradiotherapy and residual tumor
      grades in tongue carcinoma.
AB  - OBJECTIVE: The purposes of the present study were to analyze our experience with
      preoperative chemoradiotherapy followed by surgery for advanced tongue carcinoma
      and to assess the prognostic value of response to preoperative therapy in these
      tumors. STUDY DESIGN: Between May 1988 and December 1999, a total of 43 patients
      with advanced but potentially resectable squamous cell carcinoma of the tongue
      were candidates for this study. A minimum tumor size of 3 cm was required. The
      mean age was 59.8 years (range, 26-85 years); 13 cases were advanced stage II, 23
      cases were stage III, and 7 cases were stage IV. All patients were treated
      preoperatively with cisplatin- or carboplatin-based chemotherapy in combination
      with simultaneous irradiation to a target volume of 40 Gy; 2-6 weeks later, they
      underwent curative surgery. Tumor regression rate, residual tumor grade, and
      histologic regression grade to the preoperative therapy were analyzed to
      determine their influence on the prognosis. RESULTS: With a median follow-up of
      60.5 months, overall survival rates were 86.0% for all cases, 92.3% for stage II
      cases, 77.3% for stage III cases, and 100% for stage IV cases. The progression
      free survival rates according to tumor regression rate were 33.3% for group 1 (<
      50% tumor regression), 66.7% for group 2 (> or = 50% and < 75% regression), 100%
      for group 3 (> or = 75% and < 100% regression), and 96.0% for group 4 (complete
      regression). The higher the tumor regression rates, the higher the survival
      rates. When patients who achieved a regression rate of 75% or higher were
      compared with those who did not, there was a significant difference in survival
      (P < .0001). The factors of residual tumor grade and histologic regression grade
      also had good correlations with the prognosis (residual tumor grade, P =.0324;
      histologic regression grade, P < .0001). CONCLUSIONS: The findings of the present
      study suggest that response to preoperative chemoradiotherapy, such as tumor
      regression rate, residual tumor grade, and histologic regression grade, could be
      of prognostic value in patients with tongue carcinoma.

PMID- 11250627
TI  - Gastroesophageal reflux disease: New oral findings.
AB  - OBJECTIVE: The objective of this study was to investigate the effects of
      gastroesophageal reflux disease (GERD) on dentition, salivary function, and oral
      mucosa. STUDY DESIGN: Thirty-one patients with esophagitis underwent medical
      evaluation, which included taking their medical history, performing both an
      esophagogastroduodenoscopy and esophagus biopsy, and conducting a stomatologic
      examination. The latter consisted of an extraoral and intraoral physical
      examination, saliva tests (flow, buffer capacity, and pH), and biopsy and
      morphometry of the palatal mucosa, as well as taking a history of the patients'
      habits. Fourteen healthy volunteers from the same population were used as a
      control group. RESULTS: No relationship between GERD and changes in the oral
      cavity was shown by saliva tests, oral clinical examination, or histopathologic
      examination of the palatal mucosa. However, morphometric analysis of the palatal
      epithelium showed a statistically significant difference between the patients
      with GERD and the control group. CONCLUSIONS: GERD is associated with microscopic
      alterations in the palatal mucosa (epithelial atrophy and increased fibroblast
      number), which are only detected by morphometry.

PMID- 11250628
TI  - Development of a Visual Analogue Scale questionnaire for subjective assessment of
      salivary dysfunction.
AB  - OBJECTIVE: This study's objective was to develop a Visual Analogue Scale (VAS)
      xerostomia questionnaire and to evaluate the validity and reliability for the
      clinical diagnosis of salivary gland dysfunction. STUDY DESIGN: Thirty-six
      healthy adults participated in this double-blind, crossover study. Each subject
      received an antisialagogue (glycopyrrolate) or placebo. Unstimulated and
      stimulated parotid and submandibular saliva samples were collected 16 times over
      a period of 6 hours. An 8-item VAS xerostomia questionnaire was administered
      after each saliva collection. RESULTS: The results demonstrated significant
      reliability for 7 of the 8 VAS items, whereas validity was significant for
      unstimulated submandibular saliva. Moving averages were calculated for VAS and
      salivary flow rate values, and significant correlations were observed between
      these factors, indicating that changes in VAS responses were predictive of
      changes in salivary flow. CONCLUSIONS: These findings suggest that this VAS
      xerostomia questionnaire may be helpful in the diagnosis of salivary dysfunction
      and for detecting changes in salivary flow rate values over time.

PMID- 11250629
TI  - The influence of antifungal drugs on virulence properties of Candida albicans in
      patients with diabetes mellitus.
AB  - OBJECTIVE: This study investigated the influence of nystatin and fluconazole on
      virulence properties of Candida albicans. STUDY DESIGN: A total of 108 diabetic
      patients participated in the study. Eighty-eight patients had clinical oral
      candidosis. Drug therapy was given at 6 hourly intervals for nystatin or daily
      with fluconazole for a maximum of 2 weeks. Adhesion of C albicans to buccal
      epithelial cells was determined by using an autologous adhesion assay
      prospectively over 6 months. Phospholipase production was estimated by using an
      agar plate method. The data analysis included a paired Student t test and
      calculation of correlation coefficients. RESULTS: Unlike nystatin, treatment with
      fluconazole reduced the ability of C albicans to colonize the buccal mucosa for
      up to 8 weeks after the treatment. Patients without clinical signs of oral
      candidosis had significantly fewer C albicans isolates producing phospholipase
      than did patients with oral candidosis. Treatment with fluconazole, but not
      nystatin, reduced the production of phospholipase from C albicans oral isolates
      in patients with diabetes mellitus. CONCLUSIONS: In addition to being antifungal,
      fluconazole alters phospholipase production, modifies buccal epithelial cells,
      and reduces adhesion of C albicans to human buccal epithelial cells for up to 8
      weeks posttreatment in diabetic patients with oral candidosis.

PMID- 11250630
TI  - Salivary anti-spectrin autoantibodies in Sjogren's syndrome.
AB  - OBJECTIVE: The purpose of this study was done to compare the anti-spectrin
      autoantibody levels in the parotid saliva of Sjogren's syndrome patients and in
      the parotid saliva of healthy control subjects. METHODS: The salivary anti
      spectrin autoantibody levels of 20 Sjogren's patients and of 20 healthy controls
      were compared by means of the slot blot immunoassay and the alkaline phosphatase
      method. RESULTS: Various anti-spectrin autoantibody levels were detected in the
      saliva of both patients and controls. The color intensity of the blots was scored
      on a scale of 1 to 3. The scores were deemed to indicate the anti-spectrin
      autoantibody levels in saliva (1 = low, 2 = moderate, and 3 = high). The Mann
      Whitney U test did not reveal a significant difference in the anti-spectrin
      autoantibody levels of patients and the anti-spectrin autoantibody levels of
      controls (P > or = .31). These results do not support a pathologic role for anti
      spectrin autoantibody in Sjogren's syndrome. CONCLUSIONS: The overall result of
      this study substantiates that anti-spectrin autoantibodies occur naturally in
      saliva. Their role in immune surveillance or pathology is not clear at present.

PMID- 11250631
TI  - Odontogenic keratocyst: Review of 256 cases for recurrence and clinicopathologic
      parameters.
AB  - Odontogenic keratocyst (OKC) is of particular interest because of its high
      recurrence rate and aggressive behavior. Two hundred fifty-six cases of OKC were
      reviewed for the age of the patient at diagnosis, sex of the patient, OKC
      location, and radiographic findings, and 132 patients with OKC were observed to
      estimate recurrence, which was analyzed for age, sex, location, and several
      histopathologic findings. OKCs occurred more frequently in men (58.6%) than in
      women (41.4%), and they occurred in patients within a wide age range, most
      commonly in patients in the third decade of life (28.9%), followed by those in
      the second decade (25.0%); the mean age of patients with OKC was 30.8 years. One
      hundred ninety-six of the 256 cases (76.5%) occurred in the mandible, and the
      other 60 cases (23.5%) occurred in the maxilla. The mandibular molar and the
      premolar areas (51.2%) were the most common sites, and the most frequent clinical
      manifestations at first admission were swelling, pain, or both (82.4% of total
      cases). Radiographic impressions included dentigerous cyst (27.3%), OKC (25.4%),
      primordial cyst (14.8%), ameloblastoma (11.7%), residual cyst (9.8%), and
      radicular cyst (3.1%). The frequency of recurrence at the follow-up examination
      was 58.3%. There was no significant difference in the recurrence rate on the
      basis of the sex of the patient. However, OKCs had a significantly higher
      recurrence rate in patients in the fifth decade of life than in patients in the
      other age groups (P = .005).Recurrence rates were significantly dependent on the
      sites of involvement, and OKCs in the mandibular molar region had significantly
      higher recurrence rates than those in other sites (P = .001). The histopathologic
      presence of one or more daughter cysts was significantly related to recurrence (P
      = .03).

PMID- 11250632
TI  - Oral lesions indicative of plasminogen deficiency (hypoplasminogenemia).
AB  - BACKGROUND: Gingival overgrowth with ulceration has recently been recorded in 4
      reports: (1) our report of a British patient with ligneous conjunctivitis in whom
      the gingival lesions appeared to be related to tranexamic acid-an
      antifibrinolytic agent; (2) a report of 2 Turkish patients and an Italian patient
      with mainly gingival lesions; (3) our report of 5 Turkish patients with mainly
      gingival lesions; and (4) a report of 3 new Turkish cases, which also were
      associated with gingival lesions and alveolar bone loss. These patients all had
      gingival swellings, and a minority had conjunctival involvement similar to
      ligneous conjunctivitis, although the etiology was unclear in all. Nevertheless,
      fibrin exudation was fundamental because the hyaline or amyloidaceous material
      seen on the gingival biopsy stained for fibrin but failed to stain for amyloid.
      METHODS: We have examined 6 more patients who exhibited gingival swelling caused
      by amyloidaceous deposits that stained only for fibrin, and we assayed their
      plasminogen levels. RESULTS: The plasminogen functional activity assayed in these
      6 additional patients, and in 2 of the 5 patients previously reported by us, was
      significantly reduced. CONCLUSIONS: Gingival overgrowth with ulceration appears
      to be a new complication caused by plasminogen deficiency; it also appears to be
      related to ligneous conjunctivitis in some cases.

PMID- 11250633
TI  - Primary extracranial meningioma of the mandible: A report of 2 cases and a review
      of the literature.
AB  - Three cases of primary extracranial meningioma arising in the jaws have been
      reported in the English-language literature. The purpose of this report is to
      document 2 additional cases that arose in the mandible. Both cases occurred in
      women and appeared as radiolucent lesions. Microscopic examination revealed an
      unencapsulated tumor composed of uniform spindle-shaped cells arranged in whorls
      and interconnecting fascicles. Occasional nuclear pseudoinclusions and psammoma
      bodies were identified. The tumor cells demonstrated immunohistochemical
      reactivity for epithelial membrane antigen and vimentin. Both cases were treated
      by surgical excision. Based on previously published examples in the jaws, these
      neoplasms do not appear to be aggressive.

PMID- 11250634
TI  - A prognostic model for assessment of the outcome of endodontic treatment: Effect
      of biologic and diagnostic variables.
AB  - OBJECTIVE: Many biological variables, endodontic treatment factors, and
      restorative considerations have been suggested in the literature to affect the
      outcome of endodontic treatment. However, few attempts have been made recently to
      study these variables further. The purpose of this study was to identify the
      biologic and endodontic treatment-associated variables that are most predictive
      of treatment outcome for conventional endodontic therapy and to determine the
      magnitude of risk these variables pose on the outcome. STUDY DESIGN: The
      population of this historical prospective cohort study comprised a total of 200
      teeth with 441 root canals. Diagnostic and treatment information was abstracted
      from the original patient records. An endodontic follow-up examination was
      conducted 4 +/- 0.5 years after obturation. Each tooth/root was analyzed
      according to 3 indices of periradicular status at 2 time points. The main outcome
      measure was the presence of apical periodontitis. The criteria used for
      evaluation of the outcome were modified from Strindberg. Data were subjected to
      univariate and multivariate analysis. Logistic regression models were fit by
      using various clinical measures to determine which combination of biologic and
      treatment-associated factors best predicted treatment outcome. RESULTS: The
      preoperative pulp diagnosis, the periapical diagnosis, the preoperative
      periapical radiolucency size, and the sex of the patients were revealed, by means
      of univariate analysis, to exert a significant influence on endodontic treatment
      outcome (P <.05). In the logistic regression model, the strongest effect on
      postoperative healing was the presence and magnitude of preoperative apical
      periodontitis. In the presence of this variable, no other factor contributed
      value to the prediction. The correct prediction of this model was 74.7% (P <.05).
      CONCLUSION: The major biologic factors influencing the outcome of endodontic
      treatment appear to be the extent of microbiological insult to the pulp and
      periapical tissue, as reflected by the periapical diagnosis and the magnitude of
      periapical pathosis.

PMID- 11250635
TI  - Bacterial penetration of restored cavities.
AB  - The aim of this study was to assess the quality of the marginal seals of 7
      restoratives by means of a bacterial penetration test in vitro. Sixty intact
      premolars and third molars that were scheduled for extraction were used in the
      test. There were 2 experimental groups of teeth, as follows: (1) A class V
      conventional cavity and a wedge erosion cavity were prepared on the buccal
      surface and the lingual surface, respectively, of each tooth. (2) A class V
      conventional cavity and a wedge erosion cavity were prepared on the buccal
      surface and the lingual surface, respectively, of each tooth with a completely
      removed enamel layer. The cavities were then reconstructed with different
      restorative materials. The quality of the marginal seals was evaluated by
      submerging the teeth in a bacterial suspension and incubating them in an
      anaerobic milieu at 37 degrees C for 20 hours. The teeth were subsequently
      processed for histologic data and bacterial staining. The best marginal sealing
      in both the wedge erosion and the class V cavities was provided by the
      Herculite/Optibond system and the Valux Plus/Scotchbond Multipurpose system.
      Bacterial penetration was slightly greater with the Luxat compomer and the Dyrect
      compomer, as well as with Vitremer glass ionomer cement and Fuji LC glass ionomer
      cement. The bacterial penetration test showed that the use of restorative
      material does not entirely eliminate microleakage.

PMID- 11250636
TI  - Is herpes simplex virus associated with pulp/periapical inflammation?
AB  - OBJECTIVES: This study focuses on the detection of herpes simplex virus (HSV) DNA
      in dental pulp and inflamed periapical tissue. STUDY DESIGN: Dental pulp tissue
      (vital and necrotic) and periapical tissue samples were collected under strictly
      sterile conditions and examined for the presence of HSV DNA. Saliva samples were
      also examined for the presence of the viral DNA. The polymerase chain reaction
      assay was used to detect viral DNA. Blood samples were collected, and the enzyme
      linked immunosorbent assay (ELISA) for immunoglobulin G (IgG) and immunoglobulin
      M (IgM) antibodies against HSV was carried out. RESULTS: According to the ELISA
      test, 19 of the 23 blood samples were IgG-positive and IgM-negative to HSV,
      whereas 4 were IgG-negative and IgM-negative. HSV DNA was not detected in the
      tissue and the saliva samples tested. CONCLUSION: HSV is not present and
      therefore is probably not involved in the pathology of tooth neural tissue.

PMID- 11250637
TI  - Image quality assessment and radiation doses in intraoral radiography.
AB  - OBJECTIVE: The purpose of this study was to investigate 2 very important aspects
      of dental radiographic image quality, exposure time settings and film processing,
      and to assess their relation to radiation dose. STUDY DESIGN: Radiographic images
      of a dental image quality test tool were obtained in 108 dental practices. Image
      quality and film processing were evaluated both subjectively and objectively by
      comparing films developed by the dentists with films developed under optimum
      conditions. The data consisted of measured values of optical density, which were
      used to obtain image contrast, and scores of image quality and film processing,
      which were based on criteria set by 2 independent oral radiologists. Entrance
      surface dose was also measured for the technique used at each dental practice.
      RESULTS: The results indicate a great variability of exposure time settings used
      by the dentists for imaging the phantom. Film processing was inadequate in most
      of the practices, which resulted in poor image quality and increased patient
      radiation doses. The mean entrance surface dose for imaging the phantom was 3.8
      mGy. CONCLUSION: Intraoral imaging techniques and film processing must be
      standardized to improve image quality and further reduce patient radiation doses.

PMID- 11250639
TI  - Hemangiomatous ameloblastoma: Clinical, radiologic, and pathologic features.
AB  - A hemangiomatous ameloblastoma was present in the third molar region of the left
      mandible of a 26-year-old woman. The histology and radiologic features of this
      tumor differed from those of a conventional ameloblastoma. Its histologic
      features were consistent with those of a hemangiomatous ameloblastoma, and its
      standard radiologic features and computed tomography mimicked that of fibro
      osseous lesions, whereas magnetic resonance imaging suggested a vascular lesion.
      The behavior and prognosis of the hemangiomatous ameloblastoma are uncertain
      because of the small number of documented cases and lack of long-term follow-up,
      but are thought to be similar to those of the conventional type. The relevant
      clinical, radiologic, and pathologic features of this case are presented.

PMID- 11250638
TI  - Quantitative analysis of apical root resorption by means of digital subtraction
      radiography.
AB  - OBJECTIVE: This study was performed to assess the diagnostic and quantifying
      ability of digital subtraction images for simulated apical root resorption, as
      well as to compare the diagnostic accuracy of conventional intraoral radiographs
      with digital subtraction images for this condition. STUDY DESIGN: Digital and
      intraoral radiographs of 10 sound maxillary central incisors and those with
      simulated apical root resorption were taken with varying horizontal and vertical
      angulations of the x-ray beam. Paired t tests were used to compare the lengths of
      the sound teeth on the images with their actual lengths, and the estimated amount
      of simulated apical root resorption was compared with the actual amount of tooth
      loss by means of Emago software. The diagnostic accuracy for detecting lesions
      was also evaluated on conventional intraoral radiographs and digital subtraction
      images through receiver operating characteristic (ROC) analysis. RESULTS: There
      were no statistically significant differences between the actual lengths and
      those measured on the reconstructed images of the sound teeth. The calculated
      amounts of apical root resorption showed no statistically significant differences
      in comparison with the actual amounts (P >.05). The diagnostic accuracy of the
      conventional intraoral radiographs in detecting the lesions was low (ROC area =
      0.6446). CONCLUSION: A quantitative analysis of small amounts of apical root
      resorption can be performed by means of digital subtraction radiography.

PMID- 11250640
TI  - Performance of RVGui sensor and Kodak Ektaspeed Plus film for proximal caries
      detection.
AB  - OBJECTIVE: A high-resolution charge-coupled device was used to compare the
      diagnostic performances obtained with Trophy's new RVGui sensor and Kodak
      Ektaspeed Plus film with respect to caries detection. STUDY DESIGN: Three
      acquisition modes of the Trophy RVGui sensor were compared with Kodak Ektaspeed
      Plus film. Images of the proximal surfaces of 40 extracted posterior teeth were
      evaluated by 6 observers. The presence or absence of caries was scored by means
      of a 5-point confidence scale. The actual caries status of each surface was
      determined through ground-section histology. Responses were evaluated by means of
      receiver operating characteristic analysis. Areas under receiver operating
      characteristic curves (A(Z)) were assessed through analysis of variance. RESULTS:
      The mean A(Z) scores were 0.85 for film, 0.84 for the high-resolution caries
      mode, and 0.82 for both the low resolution caries mode and the high-resolution
      periodontal mode. These differences were not statistically significant (P =.70).
      The differences among observers also were not statistically significant (P =.23).
      CONCLUSION: The performance of the RVGui sensor in high- and low-resolution modes
      for proximal caries detection is comparable to that of Ektaspeed Plus film.

PMID- 11250641
TI  - Developmental regulation of corticotrophin receptor gene expression in the
      adrenal gland of the ovine fetus and newborn lamb: effects of hypoxia during late
      pregnancy.
AB  - Responsiveness of the fetal sheep adrenal gland to adrenocorticotrophin (ACTH)
      increases in late pregnancy, resulting in increased glucocorticoid production.
      Development of this responsiveness is an important determinant of fetal
      hypothalamic-pituitary-adrenal function and depends, in part, on the potential
      for ACTH binding to adrenal tissue. In the present study, we have examined the
      developmental pattern of ACTH receptor (ACTH-R) expression during the latter half
      of pregnancy and in neonatal and adult life. As hypoxaemia induces increases in
      cortisol and ACTH secretion, in addition to increasing fetal adrenal
      responsiveness, a further aim of this study was to investigate whether hypoxaemia
      was associated with altered expression of the ACTH-R gene. Whole adrenal glands
      were removed from fetal sheep, lambs and adult sheep at different stages of
      development for measurement of ACTH-R mRNA. Moderate hypoxaemia was induced for
      48 h beginning on days 124-128, or on days 132-134 of gestation, by decreasing
      the maternal fractional inspired oxygen. ACTH-R mRNA was detected by northern
      blotting using a cDNA cloned in our laboratory and by in situ hybridisation. ACTH
      R mRNA (3.6 kb major transcript) was detected in adrenal tissue at day 63 of
      gestation. Its relative abundance increased significantly (P<0.05) between days
      126-128 and 140-141 of pregnancy, increased further with the onset of spontaneous
      labour, and remained increased in newborn lambs at 7 h-7 days after birth. ACTH-R
      mRNA levels then decreased in adrenal tissue from lambs and adult sheep (P<0.05).
      Hypoxaemia for 48 h significantly increased ACTH-R mRNA expression in adrenals of
      the older fetuses (days 134-136) compared with that in controls (P<0.05), but was
      without effect in younger fetuses. We conclude that levels of ACTH-R mRNA in the
      fetal adrenal gland increase as term approaches, coincident with the endogenous
      prepartum surge in plasma ACTH and cortisol. Sustained hypoxaemia resulted in an
      upregulation of mRNA encoding for ACTH-R, but only in older fetuses and in
      association with a sustained increase in plasma cortisol. These results are
      consistent with cortisol, ACTH, or both, contributing to increased fetal adrenal
      responsiveness, by increasing expression of fetal adrenal receptors for ACTH.

PMID- 11250642
TI  - Early growth retardation induced by excessive exposure to glucocorticoids in
      utero selectively increases cardiac GLUT1 protein expression and Akt/protein
      kinase B activity in adulthood.
AB  - In the rat, dexamethasone treatment during late pregnancy leads to intrauterine
      growth retardation and is used as a model of early programming of adult onset
      disease. The present study investigated whether pre-natal dexamethasone treatment
      modifies cardiac glucose transporter (GLUT) protein expression in adulthood and
      identified signalling pathways involved in the response. Dexamethasone (100
      microg/kg body wt per day) administered via an osmotic pump to pregnant rats (day
      15 to day 21; term=22 to 23 days) reduced fetal weight at day 21 and caused
      hypertension, hyperinsulinaemia and elevated corticosterone levels in the adult
      (24-week-old) male offspring. Cardiac GLUT1 protein expression was selectively up
      regulated (2.5-fold; P<0.001), in the absence of altered cardiac GLUT4 protein
      expression, in adult male offspring of dexamethasone-treated dams. Maternal
      dexamethasone treatment did not influence cardiac GLUT1 protein expression during
      fetal or early post-natal life. We examined potential regulatory signalling
      proteins that might mediate up-regulation of cardiac GLUT1 protein expression in
      adulthood. We observed marked (2.2-fold; P<0.01) activation of Akt/protein kinase
      B (PKB), together with modest activation of the anti-apoptotic protein kinase C
      (PKC) isoforms PKC alpha (88%, P<0.05) and PKC epsilon (56%, P<0.05) in hearts of
      the early-growth-retarded male offspring. These effects were, however, observed
      in conjunction with up-regulation of cardiac protein expression of PKC beta(1)
      (191%, P<0.01), PKC beta(2) (49%, P<0.05) and PKC delta (35%; P<0.01), effects
      that may have adverse consequences. Maternal dexamethasone treatment was without
      effect on cardiac extracellular signal-related kinase (ERK) 1 or ERK2 activity in
      adulthood. In conclusion, our data demonstrate an effect of maternal
      dexamethasone treatment to up-regulate cardiac GLUT1 protein expression in early
      growth-retarded, hypertensive, hyperinsulinaemic adult male offspring, an effect
      observed in conjunction with activation of Akt/PKB.

PMID- 11250643
TI  - Proliferation, mitosis orientation and morphogenetic changes in the uterus of
      mice following chronic treatment with both estrogen and glucocorticoid hormones.
AB  - Glucocorticoids have been known to be involved in the regulation of some aspects
      of estrogen action on the uterus. However, the effect of glucocorticoids on
      changes in uterine morphogens produced by chronic estrogen exposure is not known.
      Therefore, the aim of this work was to examine the role of glucocorticoids on
      proliferative and morphogenetic uterine reactions induced by continuous estrogen
      treatment. Ovariectomized mice received subcutaneous injections of estradiol
      dipropionate in olive oil (2 microg per 100 g body weight once a week) or vehicle
      and drank water with or without dexamethasone (2 mg/l) for 30, 60 and 90 days.
      Treatment with dexamethasone caused a marked reduction in estradiol-induced
      changes in uterine weight, in proliferation (estimated from the proportion of
      mitotic and BrdU-labeled cells in all uterine tissues), and in changes in
      estradiol-dependent morphogenesis, which was redirected from the formation of
      atypical hyperplasia in animals receiving only estradiol to the appearance of
      simple or cystic endometrial hyperplasia in animals receiving both estradiol and
      dexamethasone. Estradiol alone increased dramatically the number of perpendicular
      oriented mitoses in luminal and glandular epithelia, and administration of
      dexamethasone inhibited this effect. In the absence of estradiol, chronic
      treatment with dexamethasone has no effect on all uterine parameters tested.
      Thus, chronic glucocorticoid treatment produces a complex antiestrogenic effect
      in the uterus of mice. Estradiol-induced changes in mitosis orientation are
      probably responsible for changes in the shape of glands and development of
      endometrial hyperplasia.

PMID- 11250644
TI  - The regulation by ovarian steroids of prostaglandin synthesis and prostaglandin
      induced contractility in non-pregnant rat myometrium. Modulating effects of
      isoproterenol.
AB  - The objectives of the present study were to investigate the effects of the
      reproductive steroids oestradiol and progesterone on myometrial levels of
      cyclooxygenase-2 (COX-2) mRNA and PGF(2alpha) induced myometrial contractility
      and to study whether the effect of beta(2)-adrenoceptor stimulation by
      isoproterenol on the myometrium alters these parameters. Oestrogen treatment of
      ovariectomized rats increased myometrial COX-2 mRNA whereas PGF(2alpha) receptor
      (PGF(2alpha)-R) mRNA was unchanged following this treatment and maximal
      contractility (E(max)) of isolated uterine strips challenged with PGF(2alpha) was
      unaltered. Progesterone treatment alone decreased COX-2 mRNA in comparison with
      values obtained from oestrogen-treated animals, and in combination with oestrogen
      the enhancing effect of progesterone on COX-2 mRNA was curbed. EC(50) of uterine
      strips challenged with PGF(2alpha) increased following oestrogen treatment
      whereas this parameter was substantially decreased following progesterone
      treatment. When oestrogen was combined with isoproterenol infusion mRNA values of
      both COX-2 and PGF(2alpha)-R were reduced. Finally, when isoproterenol infusions
      were given in combination with both oestrogen and progesterone, PGF(2alpha)-R
      mRNA and E(max )were enhanced as compared with similar rats not having received
      isoproterenol. We conclude that oestrogen increases COX-2 mRNA production and
      subsequent prostaglandin synthesis in non-pregnant rat myometrium. We further
      conclude that in the oestrogen-dominated rat myometrium the relaxing effect of
      beta(2)-adrenoceptor stimulation involves attenuation of both prostaglandin
      synthesis and PGF(2alpha)-R expression. We finally conclude that in the presence
      of both oestrogen and progesterone this effect of beta(2)-adrenoceptor
      stimulation is restrained.

PMID- 11250645
TI  - Mutations of ovine and bovine placental lactogens change, in different ways, the
      biological activity mediated through homologous and heterologous lactogenic
      receptors.
AB  - The biological activities of ovine (o) and bovine (b) placental lactogens (PLs)
      and their mutated analogues were compared using several binding and in vitro
      bioassays. In almost all cases, the biological activities of these analogues
      mediated through rat (r) prolactin receptor (PRLR) showed little or no change,
      despite a remarkable decrease in their capacity to bind to the extracellular
      domain of rPRLR and despite compromised stability of the 2:1 complexes. These
      results indicate that mutations impairing the ability of oPL or bPL to form
      stable complexes with lactogenic receptors do not necessarily lead to a decrease
      in the biological activity, because the transient existence of the homodimeric
      complex is still sufficient to initiate the signal transduction. In contrast, oPL
      and bPL analogues completely, or almost completely, lost their ability to
      activate homologous PRLRs, and some of them even acted as site-2 antagonists. To
      explain the difference between the activity transduced through homologous and
      that transduced through heterologous PRLRs, we propose the novel term 'minimal
      time of homodimer persistence'. This concept assumes that in order to initiate
      the signal transduction, the associated kinase JAK2 has to be transphosphorylated
      and this requires a 'minimal time' of homodimer existence. In the case of
      homologous interaction between ruminant PLs and homologous PRLRs, this 'minimal
      time' is met, though the interaction with homologous PRLRs has a shorter half
      life than that with heterologous PRLRs. Therefore oPL or bPL are active in cells
      possessing both homologous and heterologous PRLRs. Mutations of oPL or bPL lead
      to reduced affinity and, consequently, the 'time of homodimer persistence' is
      shortened. Although in the case of heterologous interaction the 'minimal time' is
      still sufficient to initiate the biological activity, in homologous interactions,
      which are already weaker than heterologous interactions, further destabilization
      of the complex shortens its persistence to below the 'minimal time', leading to
      full or partial loss of biological activity.

PMID- 11250646
TI  - beta-Subunit 102-104 residues are crucial to confer FSH activity to equine LH/CG
      but are not sufficient to confer FSH activity to human CG.
AB  - Horse LH/CG (eLH/CG) and donkey LH/CG (dkLH/CG) are strictly LH-specific in their
      respective homologous species. However, both bind to the FSH receptors from non
      equid species, whereas the zebra hormone (zbLH/CG) does not. The FSH/LH ratio of
      eLH/CG and of the alphadkbetae hybrid is about tenfold higher than that of
      dkLH/CG and of the alphaebetadk hybrid, showing that the betae subunit contains
      the structural features responsible for the high FSH activity of eLH/CG. Only six
      amino acid positions (51, 94, 95, 102, 103 and 106) are unique to the betae
      subunit when compared with the betadk and betazb subunits. The Gly-Pro and Val
      Phe sequences in positions 102-103 of betadk and betae respectively were swapped
      by site-directed mutations and the mutated beta-subunits cDNAs were cotransfected
      in COS cells with either alphae or alphadk subunit cDNA. Other mutations were
      also introduced in 102-103 dkLH/CG beta-subunit: Ala-Ala, Gly-Ala or Ala-Pro.
      These mutations with Ala-Ala, Gly-Ala or Ala-Pro in the 102-103 betadkLH/CG
      subunit did not change the FSH/LH ratio of dkLH/CG but the Gly(102)-Pro(103)-
      >Val(102)-Phe(103) mutation promoted a marked increase in the FSH/LH activity
      ratio. This was observed with the two heterodimers containing alphae or alphadk.
      Conversely, the Val(102)-Phe(103) mutation in betae led to a dramatic drop in
      FSH/LH activity ratio of eLH/CG, to a level similar to that of dkLH/CG. Since all
      FSHs possess a Gly residue at position 104, we introduced the Gly(102)-Pro(103)
      Arg(104)-->Val(102)-Phe(103)-Gly(104) mutation in betadk with the expectation
      that the increase in FSH activity observed with the Gly(102)-Pro(103)-->Val(102)
      Phe(103) mutation could be potentiated. In fact, the additional Arg(104)-
      >Gly(104) mutation was found to abolish the increase in FSH activity observed
      with Gly(102)-Pro(103)-->Val(102)-Phe(103). Mutations Gly(102)-Pro(103)-
      >Val(102)-Arg(103) or Gly(102)-Pro(103)-Lys(104)--> Val(102)-Arg(103)-Gly(104)
      were also introduced in human CGbeta (hCGbeta) to compare the impact of these
      amino acid changes in the well-studied gonadotrophin hCG. The betahCG mutants
      obtained, co-expressed either with the human or the horse alpha-subunit, did not
      display any FSH activity. In conclusion, the 102-104 sequence in eLH/CG beta
      subunits appears to be of utmost importance for their binding to FSH receptors.
      However, these results obtained with equid beta-subunits are not transposable to
      other gonadotrophins as similar mutations in hCGbeta did not lead to any increase
      in FSH activity.

PMID- 11250647
TI  - Bioavailability of oral hydrocortisone in patients with congenital adrenal
      hyperplasia due to 21-hydroxylase deficiency.
AB  - The management of congenital adrenal hyperplasia due to 21-hydroxylase (CYP21)
      deficiency requires glucocorticoid substitution with oral hydrocortisone given
      twice or thrice daily. In paediatric practice little is known of the
      bioavailability of oral hydrocortisone tablets used in these patients. The aim of
      this study was to assess the bioavailability of oral hydrocortisone and to
      evaluate current replacement therapy in the light of cortisol pharmacokinetic
      properties. We determined the bioavailability of hydrocortisone following oral
      and intravenous administration in sixteen (median age: 10.9 years, range: 6.0
      18.4 years) adequately controlled CYP21 deficient patients. Serum total cortisol
      concentrations were measured at 20-min intervals for 24 h while patients were on
      oral substitution therapy, and at 10-min intervals for 6 h following an
      intravenous bolus of hydrocortisone in a dose of 15 mg/m(2) body surface area.
      The area under the serum total cortisol concentration versus time curve (AUC)
      following oral and intravenous administration of hydrocortisone was calculated
      using the trapezoid method. The bioavailability was estimated by dividing the
      corrected for dose AUC after oral hydrocortisone administration by the corrected
      for dose AUC after the intravenous hydrocortisone administration and was
      exemplified as a percentage. After oral administration of hydrocortisone in the
      morning, median serum total cortisol concentrations reached a peak of 729.5
      nmol/l (range: 492-2520 nmol/l) at 1.2 h (range: 0.3-3.3 h) and declined
      monoexponentially thereafter to reach undetectable concentrations 7 h (range: 5
      12 h) after administration. Following administration of the evening
      hydrocortisone dose, median peak cortisol concentration of 499 nmol/l (range: 333
      736 nmol/l) was attained also at 1.2 h (range: 0.3-3.0 h) and subsequently
      declined gradually, reaching undetectable concentrations at 9 h (5-12 h) after
      administration of the oral dose. After the intravenous hydrocortisone bolus a
      median peak serum total cortisol concentration of 1930 nmol/l (range: 1124-2700
      nmol/l) was observed at 10 min (range: 10-20 min). Serum cortisol concentrations
      fell rapidly and reached undetectable levels 6 h after the hydrocortisone bolus.
      The absolute bioavailability of oral hydrocortisone in the morning was 94.2% (90%
      confidence interval (CI): 82.8-105.5%) whereas the apparent bioavailability in
      the evening was estimated to be 128.0% (90% CI: 119.0-138.0%). We conclude that
      the bioavailability of oral hydrocortisone is high and may result in
      supraphysiological cortisol concentrations within 1-2 h after administration of
      high doses. The even higher bioavailability in the evening, estimated using as
      reference the data derived from the intravenous administration of hydrocortisone
      bolus in the morning, is likely to reflect a decrease in the hydrocortisone
      clearance in the evening. Decisions on the schedule and frequency of
      administration in patients with congenital adrenal hyperplasia should be based on
      the knowledge of the bioavailability and other pharmacokinetic parameters of the
      hydrocortisone formulations currently available.

PMID- 11250648
TI  - Regulation of acute cortisol synthesis by cAMP-dependent protein kinase and
      protein kinase C in a teleost species, the rainbow trout (Oncorhynchus mykiss).
AB  - The effects of cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) on
      acute ACTH-stimulated cortisol secretion were assessed using a specific PKA
      inhibitor (H-89) and a PKC activator (phorbol 12-myristate 13-acetate, PMA) in
      dispersed head kidney cells of rainbow trout (Oncorhynchus mykiss). To
      investigate the sites of action of both PKA and PKC, pregnenolone (a cortisol
      precursor stemmed from the rate limiting step in cortisol synthesis) and 25-OH
      cholesterol (an exogenous substrate that bypasses the rate limiting step) were
      used as substrates, with and without ACTH stimulation. Inhibition of PKA
      decreased ACTH-stimulated cortisol secretion while activation of PKC had the same
      effect, demonstrating that PKA stimulates and PKC inhibits cortisol synthesis.
      Inhibition of PKA and activation of PKC had no significant effect on pregnenolone
      stimulated cortisol synthesis, indicating that both PKA and PKC act upstream from
      the pregnenolone step. Inhibition of PKA and activation of PKC had no significant
      effect on basal cortisol secretion in the presence of 25-OH-cholesterol,
      suggesting that PKA and PKC exert their effects on the mitochondrial cholesterol
      translocation step. This study provided evidence for the stimulatory role of PKA
      and the inhibitory role of PKC in the signalling pathways leading to cortisol
      synthesis in teleosts.

PMID- 11250649
TI  - Human uterine myometrial smooth muscle cell proliferation and vascular
      endothelial growth-factor production in response to platelet-derived growth
      factor.
AB  - It has been recognized that tissue-specific growth factors and angiogenic factors
      play important roles in the growth of tumors and in the tissue-repair system. In
      uterine myometrial smooth muscle cells, it has also been reported that the
      platelet-derived growth factor (PDGF) binds to PDGF receptors and stimulates
      proliferation. In this paper, we examine whether or not PDGF is able to stimulate
      production of vascular endothelial growth factor (VEGF) in cultured human
      myometrial smooth muscle cells. PDGF treatment enhanced immunoreactive VEGF
      production as well as cell proliferation. Production of VEGF121 and VEGF165 in
      the cells was detected by reverse transcription-polymerase chain reaction
      analysis, but the PDGF treatment did not change the ratio of VEGF165 to VEGF121.
      The effect of PDGF on cell proliferation leveled off at 10 ng/ml, whereas its
      effect on VEGF production continued to increase linearly at concentrations above
      10 ng/ml. Upon treatment of the cells with antibody against VEGF, the cell
      proliferation increased linearly even at PDGF concentrations above 10 ng/ml. The
      enhanced [3H]thymidine incorporation by PDGF was abolished by either mitogen
      activated protein kinase kinase (MAPKK) inhibitor or protein kinase C (PKC)
      inhibitor. In contrast, VEGF production was abolished by MAPKK inhibitor, but not
      by PKC inhibitor. These results indicate that PDGF stimulates both cell
      proliferation and VEGF production in partly different signal pathways, and thus
      PDGF might play a role in the physiology and pathology of the myometrium.

PMID- 11250650
TI  - Expression and regulation of osteopontin and connective tissue growth factor
      transcripts in rat anterior pituitary.
AB  - Cell-cell interactions are important regulatory elements in anterior pituitary
      (AP) physiology. As model systems to study pituitary cell-cell interactions, AP
      cells kept either as monolayers or as organotypic reaggregate cultures were
      analyzed by differential display PCR. We identified six cDNA fragments
      (osteopontin (Opn), connective tissue growth factor (CTGF), alpha(v)-integrin,
      cathepsin H, lysozyme and O-acetyl GD(3) ganglioside synthase) that showed
      elevated expression in monolayers compared with reaggregate cultures and the AP.
      The adenohypophyseal mRNA expression of Opn and CTGF, two secreted signaling
      substances, was studied in more detail. In situ hybridization histochemistry
      revealed that Opn mRNA expression is restricted to a subpopulation of
      gonadotropes whereas CTGF hybridization signals could not be ascribed to any
      known cell type. Opn transcript levels were downregulated in the APs of lactating
      rats and decreased when rats received s.c. injections of 17beta-estradiol for 5
      days. The mRNA expression was higher in male than in female rats and increased
      after gonadectomy. CTGF transcript levels were higher in male compared with
      female rats and were increased in pregnant rats and in rats treated for 5 days
      with triiodothyronine or dexamethasone. These results indicate that Opn and CTGF
      may be of physiological importance as local communication factors in the AP.

PMID- 11250651
TI  - Effects of sodium butyrate on expression of members of the IGF-binding protein
      superfamily in human mammary epithelial cells.
AB  - Dietary factors play an important role in both the development and prevention of
      human cancers, including breast carcinoma. One dietary micronutrient, sodium
      butyrate (NaB), is a major end product of dietary starch and fiber, produced
      naturally during digestion by anaerobic bacteria in the cecum and colon. NaB is a
      potent growth inhibitor and initiates cell differentiation for many cell types in
      vitro. In this study, we investigated the effects of NaB on three human mammary
      epithelial cells and regulation of the IGF axis, specifically, IGF-binding
      protein-3 (IGFBP-3), a known growth regulator in human mammary cells, and IGFBP
      related protein 2 (IGFBP-rP2)/connective tissue growth factor. NaB inhibited DNA
      synthesis, as measured by [3H]thymidine incorporation, in estrogen-responsive
      (MCF-7) and estrogen-non-responsive (Hs578T) breast cancer cells, and normal
      human mammary epithelial cells (HMEC) to a similar degree (up to 90% inhibition
      at 1-10 mM concentrations). Treatment of cells with NaB induced histone
      hyperacetylation, suggesting that NaB exerts its biological effects, at least in
      part, as a histone deacetylase inhibitor in mammary epithelial cells. Treatment
      of Hs578T cells with NaB caused an induction of apoptotic cell death. NaB
      treatment resulted in increased levels of p21(Waf1/Cip1) mRNA and protein in
      Hs578T cells and distinct upregulation of p27(Kip1) in HMEC, suggesting that NaB
      activates different genes involved in cell cycle arrest, depending upon the cell
      type. In the same context, among the IGFBP superfamily members tested, NaB
      specifically upregulated the expression of IGFBP-3 and IGFBP-rP2. These two
      proteins are known to be involved in inhibition of mammary epithelial cell
      replication. Northern blot analysis showed that NaB treatment at 1-10 mM
      concentrations caused a dose-dependent stimulation of IGFBP-3 mRNA expression in
      cancerous cells and IGFBP-rP2 mRNA expression in both cancerous and non-cancerous
      cells. Protein data from Western ligand blot and immunoblot analyses demonstrated
      parallel results. In summary, we have demonstrated that NaB (i) uniformly
      suppresses DNA synthesis in both cancerous and non-cancerous mammary cells, and
      (ii) upregulates IGFBP-3 and IGFBP-rP2 mRNA and protein levels in cancerous and
      non-cancerous mammary cells. These results provide the first demonstration that
      butyrate regulates the IGFBP system in the human mammary system.

PMID- 11250652
TI  - Effect of thyroxine administration on the IGF/IGF binding protein system in
      neonatal and adult thyroidectomized rats.
AB  - The effects of different doses of thyroxine (T(4)) delivered by injection or s.c.
      pellet implantation on alterations of the IGF/IGF binding protein (IGFBP) system
      were studied in neonatal and adult thyroidectomized (Tx) rats. Body weight, blood
      glucose, plasma insulin, TSH and GH and pituitary GH content, as well as serum
      IGF-I, IGF-II, IGFBP-1, -2 and -3 and their liver mRNA expression were assayed.
      Pellet implantation with the smaller dose of T(4) (1.5 microg/100 g body weight
      (b.w.) per day) in Tx neonatal rats decreased serum IGF-I, -II and the 30 kDa
      complex of IGFBPs (IGFBP-1 and -2), and increased serum IGFBP-3. Only the larger
      dose of T(4) (3 microg/100 g b.w. per day) recovered liver mRNA expression of IGF
      I and ensured euthyroid status as shown by the normalized levels of plasma TSH.
      The rapid increase of body weight and serum GH after T(4) administration
      indicated a high sensitivity to T(4) during the neonatal period. Serum and liver
      mRNA expression of IGFs and plasma insulin and GH recovered in adult Tx rats
      after pellet implantation of 1.75 microg/100 g b.w. per day throughout 10 days.
      The continuous replacement of T(4) by pellet seems to be the most suitable method
      for thyroid rehabilitation. A very good correlation was found between insulin and
      IGF-II in Tx neonates treated with T(4) but not between insulin and IGF-I in Tx
      adults. IGFBP-2 seems to be up-regulated by T(4) deprivation in neonatal and
      adult rats. Finally, a good correlation as well as a partial correlation were
      found between IGFs and thyroid hormones in both neonatal and adult Tx
      populations, suggesting a direct effect in vivo of T(4) on the hepatic secretion
      of IGFs, as previously suggested in vitro.

PMID- 11250653
TI  - Ligand-binding characteristics of recombinant amino- and carboxyl-terminal
      fragments of human insulin-like growth factor-binding protein-3.
AB  - Insulin-like growth factor-binding protein-3 (IGFBP-3) is a member of a family of
      structurally conserved proteins (IGFBP-1 to -6) which act as carriers and
      regulators of the mitogenic peptide hormones IGF-I and IGF-II. Members of the
      IGFBP family share conserved cysteine-rich amino- and carboxyl-terminal regions.
      The amino-terminal domain of these proteins is recognised to contain an IGF
      binding determinant, but evidence to support a binding site in the carboxyl
      terminal region of the protein is less rigorous. To further investigate this, we
      have synthesised both the amino-terminal (residues 1-88; N-88) and carboxyl
      terminal (residues 165-264; C-165) domains of human IGFBP-3 in bacteria, as
      fusion proteins with a carboxyl-terminal FLAG peptide. Although only C-165 showed
      binding to IGF-I and -II by solution-binding assays, both N-88 and C-165
      demonstrated binding to IGF-I and -II by biosensor analysis albeit with reduced
      affinities compared with full-length IGFBP-3. Only the carboxyl-terminal fragment
      (C-165) was able to form hetero-trimeric complexes with IGF-I and the acid-labile
      subunit (ALS). We conclude that the carboxyl-terminal domain of IGFBP-3 contains
      an IGF-binding determinant and can form ternary complexes with ALS.

PMID- 11250654
TI  - Localization of the IGF binding domain and evaluation of the role of cysteine
      residues in IGF binding in IGF binding protein-4.
AB  - Our previous findings suggest that binding of IGF binding protein-4 (IGFBP-4) to
      IGFs is essential for the inhibitory effect of IGFBP-4 on the activity of IGFs,
      both in vitro and in vivo. Therefore, understanding the structural determinants
      of IGF binding in IGFBP-4 is important to the general understanding of the
      biology of the IGF system. This study sought to further localize the IGF binding
      domain and to evaluate the role of Cys residues in IGF binding. Our data revealed
      that full-length IGFBP-4 peptides lacking the residues Leu(72)-Ser(91) or Leu(72)
      His(74) or Gly(75)-Ser(91) failed to bind to IGF-I or IGF-II, whereas deletion of
      the residue Leu(72) or residues Met(80)-Ser(91) led to a 2- to 3-fold reduction
      in IGF-I and IGF-II binding activity. The IGF-I and IGF-II binding activities
      were dramatically reduced by the single mutation, Cys9/Arg (>25-fold), and to a
      lesser degree, by the single mutation, Cys12/Arg (the first N-terminal Cys
      residue was designated Cys1). The mutation Cys17/Ser or Cys18/Tyr or Cys20/Ser
      each resulted in a similar but moderate ( approximately 5-fold) reduction in IGF
      II binding activity. The IGF-I binding activity was also dramatically reduced by
      the mutation Cys18/Tyr, and to a lesser extent, by the mutation Cys17/Ser or
      Cys20/Ser. These data suggest: 1) the IGF-I and IGF-II binding domain in IGFBP-4
      involves a hydrophobic motif (Leu(72)-Met(80)) located in the distal part of the
      conserved N-terminal region, and 2) the N-terminal Cys residues (Cys9 and Cys12)
      are more critical than the C-terminal Cys residues (Cys17 and Cys20) in affecting
      the IGF-I and IGF-II binding. Based on these data, we speculate that the
      structural determinants of IGF-I and IGF-II binding in IGFBP-4 are very similar,
      if not identical.

PMID- 11250655
TI  - Differential responsiveness of intestinal epithelial cells to 1,25
      dihydroxyvitamin D3--role of protein kinase C.
AB  - Non-transformed rat intestinal epithelial cell (IEC) lines were used to study the
      action of 1,25-dihydroxyvitamin D(3) (1,25(OH)2D) in the intestine. The capacity
      of 1,25(OH)2D to increase the expression of the cytochrome P450 component of the
      vitamin D 24-hydroxylase (CYP24) was determined in IEC-6 and IEC-18 cell lines.
      In IEC-6 cells, which are derived from crypt cells isolated from the whole small
      intestine, 1,25(OH)2D markedly increased expression of CYP24 protein and mRNA
      within 12 h. In contrast, in IEC-18 cells, which are derived from crypt cells
      from the ileum only, 1,25(OH)2D did not increase expression of CYP24 until 24-48
      h. The maximal levels of CYP24 mRNA seen in the IEC-18 cells were only 31% of the
      maximal levels seen in the IEC-6 cells. In the presence of 1,25(OH)2D, phorbol
      esters rapidly increased CYP24 mRNA levels in IEC-18 cells from almost
      undetectable to levels seen in IEC-6 cells. Protein kinase inhibitors abolished
      the stimulation by 1,25(OH)2D and by phorbol esters in both cell lines.
      Stimulation of mRNA levels by phorbol esters required new protein synthesis but
      stimulation by 1,25(OH)2D did not. These studies demonstrated that the rapid
      action of 1,25(OH)2D in IEC-6 cells is related to the activation of protein
      kinase C, an event which is missing in the IEC-18 cells. This differential
      response to 1,25(OH)2D probably takes place at a post-receptor site, since the
      number of vitamin D receptors in each cell line was found to be similar.

PMID- 11250656
TI  - Antisense knockout of HOXB4 blocks 1,25-dihydroxyvitamin D3 inhibition of c-myc
      expression.
AB  - The expression of c-myc is decreased by 1,25-(OH)2D(3) during HL-60 cell
      differentiation. Concomitantly, 1,25-(OH)2D(3) increases the expression and DNA
      binding activity of HOXB4, a homeobox gene. HOXB4 binds to the c-my c gene at
      sites involved in blocking c-myc transcription elongation. In this study, a
      phosphorothioate antisense oligonucleotide targeted against HOXB4 was examined
      for its effect on 1,25-(OH)2D(3) inhibition of c-myc expression. Alone, 1,25
      (OH)2D(3) (20 nM) increased HOXB4 levels by 103+/-7% (mean+/-s.e., n=3) and
      decreased c-myc levels by 89+/-5% (mean+/-s.e.m., n=3) at 48 h of treatment.
      HOXB4 antisense treatment completely blocked the induction of HOXB4 by 1,25
      (OH)2D(3). In addition, HOXB4 antisense partially blocked 1,25-(OH)2D(3)-mediated
      decrease in c-myc levels (46+/-6% inhibition) and promotion of HL-60 cell
      differentiation (20+/-2% and 25+/-3% inhibition as assessed by nitroblue
      tetrazolium and non-specific esterase assays respectively). The data further
      establish that HOXB4 levels are regulated by 1,25-(OH)2D(3) and reveal that HOXB4
      participates in the down-regulation of c-myc expression.

PMID- 11250657
TI  - Beneficial effect of 1,25 dihydroxyvitamin D3 on cytokine-treated human
      pancreatic islets.
AB  - We examined whether 1,25 dihydroxyvitamin D(3) (1,25 D(3)), the active form of
      vitamin D involved in the regulation of the immune system, may also protect human
      pancreatic islet cells from destruction induced by cytokines. In this study, we
      specifically investigated the effect of 1,25 D(3) on oxidative stress and major
      histocompatibility complex (MHC) induction, both implicated in cytokine-induced
      islet cell dysfunction and destruction. We also investigated the effects of 1,25
      D(3) on interleukin (IL)-6, a pleiotropic cytokine implicated in the pathogenesis
      of immunoinflammatory disorders. Human pancreatic islets, isolated from heart
      beating donors, were treated with a combination of three cytokines, IL
      1beta+tumor necrosis factor alpha+interferon gamma, in the presence or absence of
      vitamin D, and compared with with untreated control cells. Metabolic activity was
      assessed by cell viability and insulin content. Oxidative stress was estimated by
      heat shock protein 70 (hsp70) expression, cell manganese superoxide dismutase
      (MnSOD) activity and nitrite release, a reflexion of nitric oxide (NO) synthesis.
      Variation of immunogenicity of islet preparations was determined by analysis of
      the MHC class I and class II transcripts. Inflammatory status was evaluated by IL
      6 production. After 48 h of contact with cytokines, insulin content was
      significantly decreased by 40% but cell viability was not altered. MHC expression
      significantly increased six- to sevenfold as well as NO and IL-6 release (two- to
      threefold enhancement). MnSOD activity was not significantly induced and hsp70
      expression was not affected by the combination of cytokines. The addition of 1,25
      D(3) significantly reduced nitrite release, IL-6 production and MHC class I
      expression which then became not significantly different from controls. These
      results suggest that the effect of 1,25 D(3) in human pancreatic islets cells may
      be a reduction of the vulnerability of cells to cytotoxic T lymphocytes and a
      reduction of cytotoxic challenge. Hence, 1,25 D(3) might play a role in the
      prevention of type 1 diabetes and islet allograft rejection.

PMID- 11250658
TI  - Defective glucose-dependent cytosolic Ca2+ handling in islets of GK and nSTZ rat
      models of type 2 diabetes.
AB  - We examined to what extent the abnormal glucose-dependent insulin secretion
      observed in NIDDM (non-insulin-dependent diabetes mellitus) is related to
      alterations in the handling of cytosolic Ca2+ of islets of Langerhans. Using two
      recognized rat models of NIDDM, the GK (Goto-Kakizaki) spontaneous model and the
      nSTZ (neonatal streptozotocin) induced model, we could detect several common
      alterations in the glucose-induced [Ca2+]i cytosolic responses. First, the
      initial reduction of [Ca2+]i following high glucose (16.7 mM) observed routinely
      in islets obtained from non-diabetic Wistar rats could not be detected in GK and
      nSTZ islets. Second, a delayed response for glucose to induce a subsequent 3%
      increase of [Ca2+]i over basal level was observed in both GK (321+/-40 s, n=11)
      and nSTZ (326+/-38 s, n=13) islets as compared with Wistar islets (198+/-20 s,
      n=11), values representing means+/-s.e.m. Third, the rate of increase in [Ca2+]i
      in response to a high glucose challenge was 25% and 40% lower in GK and nSTZ
      respectively, as compared with Wistar islets. Fourth, the maximal [Ca2+](i) level
      reached after 10 min of perifusion with 16.7 mM glucose was lower with GK and
      nSTZ islets and represented respectively 60% and 90% of that of Wistar islets.
      Further, thapsigargin, a blocker of Ca2+/ATPases (SERCA), abolished the initial
      reduction in [Ca2+]i observed in response to high glucose and induced fast
      [Ca2+]i oscillations with high amplitude in Wistar islets. The latter effect was
      not seen in GK and nSTZ islets. In these two NIDDM models, several common
      alterations in glucose-induced Ca2+ handling were revealed which may contribute
      to their poor glucose-induced insulin secretion.

PMID- 11250659
TI  - Coronary vasodilation and positive inotropism by urocortin in the isolated rat
      heart.
AB  - Corticotropin-releasing factor (CRF) has a coronary vasodilator effect and a
      positive inotropic effect on the isolated rat heart. Recently, expression of CRF
      receptor type 2 (CRF-R2) has been demonstrated in the heart. In addition,
      urocortin (Ucn), a new member of the CRF family, has been reported to have much
      greater affinity for CRF-R2 than CRF. It is suggested that the cardiac effects of
      Ucn may be more potent than those of CRF. We compared the effect of Ucn with that
      of CRF on isolated rat heart. The effects of Ucn were then analyzed to determine
      whether these effects were mediated by CRF receptors and/or any other mediators
      under the following conditions: perfusion buffer containing (1) alpha-helical CRF
      9-41, (2) indomethacin, (3) N(G)-nitro-l -arginine methylester and (4)
      propranolol. Ucn exhibited a greater effect with a longer duration of action than
      CRF. Indomethacin significantly attenuated the vasodilator effects of Ucn
      (P<0.05). CRF receptor antagonist diminished both coronary vasodilation and the
      positive inotropic effects of Ucn (P<0.05). These results suggest that the
      cardiac effects of Ucn may be mediated by a CRF receptor, and prostaglandins may
      be involved in the vasodilator effect.

PMID- 11250660
TI  - Endomorphins and activation of the hypothalamo-pituitary-adrenal axis.
AB  - Endomorphin (EM)-1 and EM-2 are opioid tetrapeptides recently located in the
      central nervous system and immune tissues with high selectivity and affinity for
      the mu-opioid receptor. Intracerebroventricular (i.c.v.) administration of
      morphine stimulates the hypothalamo-pituitary-adrenal (HPA) axis. The present
      study investigated the effect of centrally administered EM-1 and EM-2 on HPA axis
      activation. Rats received a single i.c.v. injection of either EM-1 (0.1, 1.0, 10
      microg), EM-2 (10 microg), morphine (10 microg), or vehicle (0.9% saline). Blood
      samples for plasma corticosterone determinations were taken immediately prior to
      i.c.v. administration and at various time points up to 4 h post-injection. Trunk
      blood, brains and pituitaries were collected at 4 h. Intracerebroventricular
      morphine increased plasma corticosterone levels within 30 min, whereas EM-1 and
      EM-2 were without effect. In addition, pre-treatment of i.c.v. EM-1 did not block
      the rise in corticosterone after morphine. Corticotrophin-releasing factor (CRF)
      mRNA and arginine vasopressin (AVP) mRNA in the paraventricular nucleus (PVN) and
      POMC mRNA in the anterior pituitary were found to be unaffected by either
      morphine or endomorphins. Since release of other opioids are elevated in response
      to acute stress, we exposed rats to a range of stressors to determine whether
      plasma EM-1 and EM-2 can be stimulated by HPA axis activation. Plasma
      corticosterone, ACTH and beta-endorphin were elevated following acute restraint
      stress, but concentrations of plasma EM-1-immunoreactivity (ir) and EM-2-ir did
      not change significantly. Corticosterone, ACTH and beta-endorphin were further
      elevated in adjuvant-induced arthritis (AA) rats by a single injection of
      lipopolysaccharide (LPS), but not by restraint stress. In conclusion, neither EM
      1 or EM-2 appear to influence the regulation of the HPA axis. These data suggest
      that endomorphins may be acting on a different subset of the mu-opioid receptor
      than morphine. The failure to induce changes in plasma EM-ir in response to the
      chronic inflammatory stress of AA, the acute immunological stress of LPS, or the
      psychological stress of restraint, argues against an important role for
      endomorphins in mediating HPA axis activity.

PMID- 11250661
TI  - The pituitary-thyroid axis in healthy men living under subarctic climatological
      conditions.
AB  - In order to evaluate the effects of climatic factors on the secretion of thyroid
      hormones and TSH in a high latitude population, we have taken serum and urine
      samples from 20 healthy men from northern Finland (67 degrees -68 degrees N)
      every 2 months for a period of 14 months. Serum free triiodothyronine (T(3))
      levels were lower in February than in August (3.9 vs 4.4 pmol/l, P<0.05) and TSH
      levels were higher in December than during other months (2.1 vs 1.5-1.7 mU/l,
      P<0.01). Serum total and free thyroxine (T(4)), total T(3) and reverse T(3)
      levels and urinary T(4) levels were unchanged. Urinary T(3) levels were
      significantly higher in winter than in summer. Serum free T(3) correlated highly
      significantly with the outdoor temperature integrated backwards weekly for 7-56
      days (r=0.26 for 1-56 days) from the day when the blood samples were taken. Serum
      TSH did not show any significant correlation with the thyroid hormones or with
      the integrated temperature of the previous days, but it did show an inverse and
      significant correlation (r=-0.31) with the ambient luminosity integrated
      backwards for 7 days from the day when the blood sample was taken. The gradually
      increasing correlation between outdoor temperatures and serum free T(3) suggests
      that the disposal of thyroid hormones is accelerated in winter, leading to low
      serum free T(3) levels and a high urinary free T(3) excretion. Since there was no
      correlation between thyroid hormones and serum TSH, the feedback mechanism
      between TSH and thyroid hormones may not be the only contributing factor, and
      other factors such as ambient luminosity may at least partly determine serum TSH
      in these conditions. Also urinary free T(3) appears to be a novel and non
      invasive indicator for thyroid physiology.

PMID- 11250662
TI  - Environment and medication use influence olfactory abilities of older adults.
AB  - BACKGROUND: Age-associated changes in eating behavior and nutritional status are
      often caused by changes in olfactory perception. OBJECTIVE: This study determined
      the relative contribution of medication use and environmental risk to age
      associated change in olfaction. DESIGN: Fifty participants aged 50-96 (M = 70.4)
      in two groups (environmentally at-risk and low-risk) were administered a set of
      four olfactory tasks, WAIS Vocabulary, MMSE, and demographic questionnaires.
      Environmental risk was defined as having worked in places where exposure to
      caustic fumes (e.g., formaldehyde, toluene, etc.) was common and long-term.
      Olfactory tasks included detection thresholds for phenethyl alcohol (PEA;
      assesses olfactory function) and menthol (assesses olfactory and trigeminal
      function); odor recognition in a forced-choice paradigm; odor difference
      discrimination; and odor identification with supplied names. RESULTS: The high
      risk group had significantly higher thresholds for PEA, and significant within
      group variability for menthol. Medication usage and cognitive status were
      significantly associated with odor recognition. Only medication was strongly
      associated with the odor discrimination task. Medication usage, environmental
      risk, and age in order were found to be the greatest risk factors for odor
      identification. CONCLUSION: These results highlight the need to carefully
      consider environmental and pharmacological effects in age-associated sensory
      tasks.

PMID- 11250663
TI  - The independent older Australian: Implications for food and nutrition
      recommendations.
AB  - The World Health Organisation has restructured their program for health and the
      elderly, renaming it Aging and Health, focussing on aging as a part of life
      rather than a static age group separated from the rest of the population. As the
      older population becomes more heterogeneous, nutrition and food service providers
      in the community are faced with new challenges. This paper presents nutrition
      recommendations relevant to community nutrition programs in Australia including
      the recently released Dietary Guidelines for Older Australians. The subsequent
      discussion focuses on issues associated with implementation of community based
      food and nutrition intervention programs. The following strategies for successful
      implementation of community based food and nutrition programs were identified:
      Meals on Wheels services. 1. should maintain a register of food service systems
      for each site to assist in the planning process. 2. Develop a procedure for the
      nutritional assessment of menus focussing on a standardised methodology and
      recipes as well as ensuring trained staff are available to apply the procedure.
      3. Validate recommended serving sizes and recommend serving utensils for specific
      menu items. Provide advice on the purchasing, use and calibration of scales as
      well as containers. 4. Develop alternative, informal methods of assessing client
      satisfaction to ensure the clients' experience with the service, rather than
      their reaction to the experience, be assessed. 5. Develop a management training
      program which focuses on a "train-the-trainer' strategy to ensure continuous, on
      site training. Meeting the nutritional needs of the heterogeneous group of older
      people implies a modified approach to nutritional support. All those involved in
      community nutrition organisations need to recognise the significance of the
      "caring" role as well as that of food provider and the impact of this on the
      nutritional status of the client. The development of consistent guidelines and
      tools will assist organisations in meeting the needs of their target groups. As
      professionals we need to understand and accept the constraints that these
      organisations deal with to ensure the services we provide are appropriate. These
      constraints include all of those issues detailed in this paper - production
      capability, training resources and the availability of volunteers.

PMID- 11250664
TI  - Does low lactose milk powder improve the nutritional intake and nutritional
      status of frail older Chinese people living in nursing homes?
AB  - BACKGROUND: Malnutrition is prevalent among nursing home residents in Hong Kong.
      Nutrient dense oral supplements and yoghurt are unpopular among the Chinese older
      people because of their unfamiliar tastes and relatively high costs. Vitamin and
      mineral supplements do not address the problem of protein calorie undernutrition.
      Milk powder may be a suitable alternative supplement, but diarrhoea resulting
      from lactase deficiency is common in Chinese people. OBJECTIVE: We hypothesized
      that a low lactose milk powder would be better tolerated in Chinese nursing home
      residents and result in improvement in nutritional intake without reducing
      habitual intake. DESIGN: Forty-seven residents were randomized to receive milk
      powder twice daily, or no supplement for seven weeks. Twenty-four hour food
      record, body weight, upper limb skinfold thicknesses and midarm circumference,
      grip strength, Barthel Index, and abbreviated mental test score were carried out
      at baseline and at seven weeks. RESULTS: The overall compliance was nearly 100%,
      and no subjects developed diarrhoea. Compared with controls, milk supplementation
      increased intake of calcium, vitamin D, vitamin A, riboflavin and potassium.
      There was no significant reduction in habitual dietary intake in supplemented
      subjects. There was a trend of weight gain in supplemented subjects, though this
      did not reach statistical significance. There was no change in handgrip strength,
      mental function and disability level. CONCLUSION: The study shows that low
      lactose milk powder is a well-accepted nutritional supplement without reducing
      habitual dietary intake.

PMID- 11250665
TI  - Assessing appetite in Dutch elderly with the Appetite, Hunger and Sensory
      Perception (AHSP) questionnaire.
AB  - BACKGROUND: In investigating anorexia of ageing, attention is often given to
      physical and psychological determinants of appetite in the elderly but little has
      been done to provide information on self-assessment of appetite and sensory
      perceptions in the elderly. OBJECTIVES: to provide data and detect possible
      differences in self-assessment of appetite, hunger feelings and sensory
      perception in different health group of elderly using the Appetite, Hunger
      feelings and Sensory Perception (AHSP) questionnaire. METHODS: three health
      categories of elderly subjects were used for the present study: free-living with
      no help, free-living with help and nursing home elderly. For each group,
      collected data were general characteristics, anthropometry and answers to the
      AHSP. The AHSP questionnaire includes 29-items focusing on feelings of hunger and
      appetite as well as taste and smell perception addressing both the present
      situation and the period before retirement. RESULTS: Significant differences were
      observed between the 3 health groups for appetite, hunger feelings, present taste
      perception and present smell perception (P<0.05). Appetite and hunger were found
      to be related to body weight in the healthiest but not in the others. CONCLUSION:
      A decline in health status is paired with a decrease in appetite, hunger feelings
      and sensory perceptions of elderly subjects.

PMID- 11250666
TI  - Serum leptin levels in the elderly: relationship with gender and nutritional
      status.
AB  - PURPOSE: Assessment of whether, there is a positive correlation between serum
      leptin levels, and BMI or/ nutritional status in the elderly as reported for the
      younger population. METHODS: A cross-sectional study, conducted in 62 elderly
      residents of a nursing home in Israel, and the subjects were divided into three
      different categories according to BMI. Serum leptin and other biochemical
      parameters were assessed. Correlation was calculated by the Pearson's correlation
      coefficients and statistical analysis by paired Student's t test. The
      relationship of BMI, leptin levels and nutritional status was determined.
      RESULTS: Significant differences between men and women were obtained for weight,
      total energy intake, carbohydrates, cholesterol and leptin. Serum leptin levels
      in women were three times higher than in men and higher compared with to their
      respective parallel BMI categories in men. A positive correlated scattering
      between BMI and leptin levels (r=0.65, p< 0.0001) was shown only for the
      different BMI categories in women. CONCLUSIONS: In the elderly, as in the young
      population, a positive correlation was obtained for BMI and leptin. In addition,
      significantly higher differences in circulating leptin were found in the women
      compared with the consistently low levels found in the men. The results suggest
      that female hormones do not play a significant role in determining serum leptin
      levels.

PMID- 11250667
TI  - Survival prognostic value of serum interleukin-6 level in very old people.
AB  - OBJECTIVE: To determine the survival prognostic value of serum interleukin-6
      level in very old people. DESIGN: Prospective 12-month clinical survey in a long
      term ward and in a day care hospital. SETTING: A long-term ward and a day care
      hospital for very old and dependent people, located in Poitiers (France).
      PARTICIPANTS: A cohort of 115 old people [Range 64-101], either in a long-term
      ward (n=71) or in day care hospital (n=44). MEASUREMENTS: Patients were checked
      for different nutritional parameters and the Interleukin-6 level in the serum at
      baseline and patients were followed up for one year. RESULTS: A high level of
      interleukin-6 (Il-6) is associated with increased Prognostic Inflammatory and
      Nutritional Index (PINI) value, serum CRP thereby demonstrating the inflammatory
      role of this molecule. It is also associated with an increased risk of death.
      Using a survival regression model, a high Il-6 serum level observed at the
      beginning of the study is a bad prognostic indicator, with other biological or
      nutritional parameters having no significant influence. CONCLUSION: A high level
      of Interleukin-6 may be a better marker of prognosis than an increased PINI
      score.

PMID- 11250668
TI  - A follow-up study of ulcer healing, nutrition, and life-situation in elderly
      patients with leg ulcers.
AB  - This study was undertaken in order to follow up ulcer healing, ulcer recurrence,
      nutritional status and life-situation in elderly patients with leg ulcers. Of 70
      patients assessed previously in 1996, 43 (61%) were still alive in 2000 and, of
      these, 38 (88%) participated in the follow-up. Rate of healing, recurrence and
      amputation were obtained from medical records and interviews with the patients.
      The Mini Nutritional Assessment (MNA) was used to assess their nutritional status
      and the Philadelphia Geriatric Center Multilevel Assessment Instrument was used
      for assessment of their life-situation. Nineteen patients (50%), mean age 82+/
      4.6 years, had healed ulcers. Two (5%) patients, mean age 86+/-2.8, had required
      amputation and had no ulceration after surgery. Seventeen patients (45%), mean
      age 80.3+/-6 years, had open ulcers, six had their original ulcers still
      unhealed, and 11 had open recurrent ulcers. Decreased mean MNA scores, as well as
      decreased mean scores in ADL and mobility, were seen over time in patients with
      open ulcers but not in those who were healed. Patients with healed ulcers had
      significantly higher mean scores in social interaction than those with open
      ulcers and significantly increased mean scores in environmental quality over
      time. The results indicate that nutrition and the life-situation might be related
      to leg ulcer healing. The nutritional situation and the whole life-situation
      should be observed and taken into consideration when care is planned. Additional
      research is needed to increase the understanding of the relationship between
      nutrition, life-situation and ulcer healing.

PMID- 11250669
TI  - Leptin and anti-aging action of caloric restriction.
AB  - Evolutional theories of aging and caloric restriction (CR) in animals predict the
      presence of neuroendocrine signals to divert the limited energy resources from
      energy-costly physiologic processes such as reproduction to those essential for
      survival in response to food shortage. The diversion of energy and subsequent
      molecular mechanisms might extend the lifespan. A growing body of evidence
      indicates that leptin, a peptide hormone secreted from adipocytes, has a key role
      in neuroendocrine adaptation against life-threatening stress such as fasting. The
      present review discusses the potential role of leptin in the anti-aging action of
      CR. Although several alternative signaling pathways might also mediate the anti
      aging action of CR, leptin signaling could be a substantial pathway in the CR
      action. Research on neuroendocrine mechanisms of CR is warranted, because such
      efforts might provide clues to the regulation of the aging process in humans.

PMID- 11250670
TI  - Pre-operative nutritional assessment in the elderly.
AB  - Nutritional depletion has been frequently documented in adult surgical patients
      admitted to hospital with nutritional status being known to deteriorate over the
      course of the hospital stay. In the elderly in particular, undernutrition has
      serious implications for health and for recovery from illness or surgery. This,
      in turn, has cost implications for the health service and the efficient
      distribution of health care. Because nutritional depletion is often insidious,
      nutritional problems frequently go unrecognised and untreated. Nutritional
      screening and assessment of nutritional status should therefore form an essential
      part of the health care of any elderly patient who requires surgical
      intervention. This paper aims to review the screening and assessment techniques
      currently available and their applicability to the elderly surgical patient.

PMID- 11250672
TI  - Do we now have a relevant animal model for breast cancer?

PMID- 11250673
TI  - Bringing estrogen receptors under control.

PMID- 11250674
TI  - Killing the umpire: cooperative defects in mitotic checkpoint and BRCA2 genes on
      the road to transformation.
AB  - Recent findings from mouse models of BRCA2 genetic lesions have provided
      intriguing insights and important questions concerning modes of tumor development
      in familial breast and ovarian cancers. Fibroblasts from mice homozygous for the
      BRCA2Tr allele grow poorly and display an array of chromosomal abnormalities that
      are consistent with a role for BRCA2 in DNA repair. This growth defect can be
      overcome and cellular transformation promoted by the expression of defective,
      dominant negative alleles of p53 and of the mitotic checkpoint gene Bub1, both of
      which are known to induce chromosome instability. These findings are mirrored in
      the genetic lesions sustained in tumors found in the rare BRCA2Tr/Trmice that
      survive to adulthood, which include defects in p53 as well as the mitotic
      checkpoint proteins Bub1 and Mad3L. Together, these data hint that tumors in
      these mice evolve from an unusually intense selective pressure to remove DNA
      damage checkpoints, which in turn might be facilitated by chromosomal abolition
      of mitotic checkpoints and the consequent increase in shuffling of genetic
      information. How these genetic lesions co-operate to yield transformed cells and
      how these data relate to BRCA1 and BRCA2 defects in the human population are
      important questions raised by this work.

PMID- 11250675
TI  - Epithelial stem cells in the mammary gland: casting light into dark corners.
AB  - The epithelial structures of the human breast or the mouse mammary gland are
      derived from a relatively small number of multipotent, tissue-specific stem
      cells, of which we are surprisingly ignorant. We do not know how many are
      required to produce a complete mammary gland, how many times they divide during
      the process, where they are situated in the gland, or even what they look like.
      We want to know the answers to these questions, not just to satisfy intellectual
      curiosity, but also because the answers may shed light on the evolution of breast
      cancer. Now, studies carried out by Kordon and Smith at the National Cancer
      Institute have pointed the way toward a new understanding of mammary stem cells
      and their progeny.

PMID- 11250676
TI  - How many more breast cancer predisposition genes are there?

PMID- 11250677
TI  - Endogenous hormones and the aetiology of breast cancer.

PMID- 11250678
TI  - Opinion: why the variation in breast cancer survival in Europe?

PMID- 11250679
TI  - The pathology of familial breast cancer: The pre-BRCA1/BRCA2 era: historical
      perspectives.
AB  - A proportion of breast carcinomas develop as a result of a genetic predispostion
      to the disease. Prior to cloning of the BRCA1 and BRCA2 genes a limited number of
      studies were carried out to identify specific histopathological characteristics
      of hereditary breast cancer. These studies are the subject of this review. The
      main finding was the association of the (atypical) medullary type of breast
      cancer with a family history; the most important caveat being that medullary
      breast cancer is found more frequently in young patients. In view of the frequent
      bilateral occurrence of lobular cancer, this histologic type is also likely to be
      associated with a predisposing genetic defect. Future investigations will have to
      test this hypothesis. In addition to mutations in the BRCA1 and BRCA2 genes,
      there are as yet unidentified genetic defects predisposing to breast cancer
      development, and histopathology may well help in identifying these genes in the
      future.

PMID- 11250680
TI  - The pathology of familial breast cancer: Morphological aspects.
AB  - A small proportion of breast cancers are due to a heritable predisposition.
      Recently, two predisposition genes, BRCA1 and BRCA2, have been identified and
      cloned. The morphological features of tumours from patients harbouring mutations
      in the BRCA1 and BRCA2 genes differ from each other and from sporadic breast
      cancers. Both are of higher grade than are sporadic cases. An excess of
      medullary/atypical medullary carcinoma has been reported in patients with BRCA1
      mutations. Multifactorial analysis, however, shows that the only features
      independently associated with BRCA1 mutations are a high mitotic count, pushing
      tumour margins and a lymphocytic infiltrate. For BRCA2 mutation, an association
      with tubular/lobular carcinoma has been suggested, but not substantiated in a
      larger Breast Cancer Linkage Consortium study. In multifactorial analysis, the
      independent features were a lack of tubule formation and pushing tumour margins
      only. The morphological analysis has implications for clinical management of
      patients.

PMID- 11250681
TI  - The pathology of familial breast cancer: Immunohistochemistry and molecular
      analysis.
AB  - Extensive studies of BRCA1- and BRCA2-associated breast tumours have been carried
      out in the few years since the identification of these familial breast cancer
      predisposing genes. The morphological studies suggest that BRCA1 tumours differ
      from BRCA2 tumours and from sporadic breast cancers. Recent progress in
      immunohistochemistry and molecular biology techniques has enabled in-depth
      investigation of molecular pathology of these tumours. Studies to date have
      investigated issues such as steroid hormone receptor expression, mutation status
      of tumour suppressor genes TP53 and c-erbB2, and expression profiles of cell
      cycle proteins p21, p27 and cyclin D1. Despite relative paucity of data, strong
      evidence of unique biological characteristics of BRCA1-associated breast cancer
      is accumulating. BRCA1-associated tumours appear to show an increased frequency
      of TP53 mutations, frequent p53 protein stabilization and absence of
      imunoreactivity for steroid hormone receptors. Further studies of larger number
      of samples of both BRCA1- and BRCA2-associated tumours are necessary to clarify
      and confirm these observations.

PMID- 11250683
TI  - The pathology of familial breast cancer: Clinical and genetic counselling
      implications of breast cancer pathology.
AB  - Approximately 5% of all breast cancers are due to one of the high-risk breast
      cancer genes BRCA1 and BRCA2, or possibly to a third or fourth moderate- to high
      risk gene(s). A further proportion of cases arise in the presence of a less
      striking family history, with later average age at onset and lower penetrance:
      familial breast cancer. Bilaterality is a recognized feature of hereditary breast
      cancer. Cancers often present at an early age, with the contralateral risk high
      within 10 years. Proof that bilateral malignancies are separate primaries can be
      difficult histologically, however, especially within 3 years. The recent finding
      of specific pathological features related to BRCA1 and, to a lesser extent, BRCA2
      mutations means that, in addition to bilaterality and family history, a
      pathological element can be entered into the risk calculation for the presence of
      BRCA1/BRCA2 mutations. This will facilitate the targeting of mutation testing to
      families in which a positive result is most likely, and may subsequently
      influence the clinical management of these families.

PMID- 11250682
TI  - The pathology of familial breast cancer: How do the functions of BRCA1 and BRCA2
      relate to breast tumour pathology?
AB  - Women with mutations in the breast cancer susceptibility genes, BRCA1 and BRCA2,
      have an increased risk of developing breast cancer. Both BRCA1 and BRCA2 are
      thought to be tumour suppressor genes since the wild type alleles of these genes
      are lost in tumours from heterozygous carriers. Several functions have been
      proposed for the proteins encoded by these genes which could explain their roles
      in tumour suppression. Both BRCA1 and BRCA2 have been suggested to have a role in
      transcriptional regulation and several potential BRCA1 target genes have been
      identified. The nature of these genes suggests that loss of BRCA1 could lead to
      inappropriate proliferation, consistent with the high mitotic grade of BRCA1
      associated tumours. BRCA1 and BRCA2 have also been implicated in DNA repair and
      regulation of centrosome number. Loss of either of these functions would be
      expected to lead to chromosomal instability, which is observed in BRCA1 and BRCA2
      associated tumours. Taken together, these studies give an insight into the
      pathogenesis of BRCA-associated tumours and will inform future therapeutic
      strategies.

PMID- 11250684
TI  - Mouse models for breast cancer.

PMID- 11250685
TI  - Microarray foray.

PMID- 11250686
TI  - Breast cancer prevention.

PMID- 11250687
TI  - Beyond the genome to tissue proteomics.

PMID- 11250688
TI  - Gene therapy for carcinoma of the breast: Genetic immunotherapy.
AB  - Advances in gene transfer technology have greatly expanded the opportunities for
      developing immunotherapy strategies for breast carcinoma. Genetic immunotherapy
      approaches include the transfer of genes encoding cytokines and costimulatory
      molecules to modulate immune function, as well as genetic immunization strategies
      which rely on the delivery of cloned tumor antigens. Improved gene transfer
      vectors, coupled with a better understanding of the processes that are necessary
      to elicit an immune response and an expanding number of target breast tumor
      antigens, have led to renewed enthusiasm that effective immunotherapy may be
      achieved. It is likely that immunotherapeutic interventions will find their
      greatest clinical application as adjuvants to traditional first-line therapies,
      targeting micrometastatic disease and thereby reducing the risk of cancer
      recurrence.

PMID- 11250689
TI  - Gene therapy for carcinoma of the breast: Genetic toxins.
AB  - Gene therapy was initially envisaged as a potential treatment for genetically
      inherited, monogenic disorders. The applications of gene therapy have now become
      wider, however, and include cardiovascular diseases, vaccination and cancers in
      which conventional therapies have failed. With regard to oncology, various gene
      therapy approaches have been developed. Among them, the use of genetic toxins to
      kill cancer cells selectively is emerging. Two different types of genetic toxins
      have been developed so far: the metabolic toxins and the dominant-negative class
      of toxins. This review describes these two different approaches, and discusses
      their potential applications in cancer gene therapy.

PMID- 11250690
TI  - Gene therapy for carcinoma of the breast: Therapeutic genetic correction
      strategies.
AB  - Gene therapy is a therapeutic approach that is designed to correct specific
      molecular defects that contribute to the cause or progression of cancer. Genes
      that are mutated or deleted in cancers include the cancer susceptibility genes
      p53 and BRCA1. Because mutational inactivation of gene function is specific to
      tumor cells in these settings, cancer gene correction strategies may provide an
      opportunity for selective targeting without significant toxicity for normal
      nontumor cells. Both p53 and BRCA1 appear to inhibit cancer cells that lack
      mutations in these genes, suggesting that the so-called gene correction
      strategies may have broader potential than initially believed. Increasing
      knowledge of cancer genetics has identified these and other genes as potential
      targets for gene replacement therapy. Initial patient trials of p53 and BRCA1
      gene therapy have provided some indications of potential efficacy, but have also
      identified areas of basic and clinical research that are needed before these
      approaches may be widely used in patient care.

PMID- 11250693
TI  - Breast cancer research: where we are and where we should go.

PMID- 11250691
TI  - Gene therapy for carcinoma of the breast: Pro-apoptotic gene therapy.
AB  - The dysregulation of apoptosis contributes in a variety of ways to the malignant
      phenotype. It is increasingly recognized that the alteration of pro-apoptotic and
      anti-apoptotic molecules determines not only escape from mechanisms that control
      cell cycle and DNA damage, but also endows the cancer cells with the capacity to
      survive in the presence of a metabolically adverse milieu, to resist the attack
      of the immune system, to locally invade and survive despite a lack of tissue
      anchorage, and to evade the otherwise lethal insults induced by drugs and
      radiotherapy. A multitude of apoptosis mediators has been identified in the past
      decade, and the roles of several of them in breast cancer have been delineated by
      studying the clinical correlates of pathologically documented abnormalities.
      Using this information, attempts are being made to correct the fundamental
      anomalies at the genetic level. Fundamental to this end are the design of more
      efficient and selective gene transfer systems, and the employment of complex
      interventions that are tailored to breast cancer and that are aimed concomitantly
      towards different components of the redundant regulatory pathways. The
      combination of such genetic modifications is most likely to be effective when
      combined with conventional treatments, thus robustly activating several pro
      apoptotic pathways.

PMID- 11250692
TI  - Gene therapy for carcinoma of the breast: Genetic ablation strategies.
AB  - The gene therapy strategy of mutation compensation is designed to rectify the
      molecular lesions that are etiologic for neoplastic transformation. For dominant
      oncogenes, such approaches involve the functional knockout of the dysregulated
      cellular control pathways provoked by the overexpressed oncoprotein. On this
      basis, molecular interventions may be targeted to the transcriptional level of
      expression, via antisense or ribozymes, or post-transcriptionally, via
      intracellular single chain antibodies (intrabodies). For carcinoma of the breast,
      these approaches have been applied in the context of the disease linked oncogenes
      erbB-2 and cyclin D1, as well as the estrogen receptor. Neoplastic revision
      accomplished in modal systems has rationalized human trials on this basis.

PMID- 11250695
TI  - Caretaker Brca1: keeping the genome in the straight and narrow.
AB  - Inheritance of germline BRCA1 mutations is associated with a high risk of breast
      and ovarian cancers. A multitude of cellular functions has been ascribed to
      BRCA1, including transcription activation and various aspects of DNA repair. So
      far, indirect evidence has indicated a role for BRCA1 in the repair of double
      strand breaks. Recently, an elegant gene targeting design was used to provide
      definitive evidence that BRCA1 promotes homologous recombination and limits
      nonhomologous mutagenic repair processes. This reaffirms the role of BRCA1 as
      caretaker in preserving genomic integrity.

PMID- 11250694
TI  - Founder populations and their uses for breast cancer genetics.
AB  - Numerous founder mutations have been reported in BRCA1 and BRCA2. For genetic
      screening of a population with a founder mutation, testing can be targeted to the
      mutation, allowing for a more rapid and less expensive test. In addition, more
      precise estimates of the prior probability of carrying a mutation and of the
      likelihood of a mutation carrier developing cancer should be possible. For a
      given founder mutation a large number of carriers are available, so that focused
      scientific studies of penetrance, expression, and genetic and environmental
      modifiers of risk can be performed. Finally, founder populations may be a
      powerful resource to localize additional breast cancer susceptibility loci,
      because of the reduction in locus heterogeneity.

PMID- 11250697
TI  - Transforming growth factor-beta and breast cancer: Introduction.

PMID- 11250696
TI  - Signal transducers and activators of transcription as regulators of growth,
      apoptosis and breast development.
AB  - STAT transcription factors were discovered 10 years ago as mediators of
      interferon-induced gene expression. They now form an important group, comprising
      seven members, that are activated by virtually every cytokine and growth factor.
      Their critical role in development and normal cell signaling has been largely
      determined through the analysis of transgenic mice lacking individual STAT genes.
      In addition, cell culture work has further delineated their importance in
      cellular transformation, apoptosis, differentiation and growth control. This
      review discusses the specific phenotypes of STAT-deficient animals with a focus
      on STAT5 and STAT3, as these two STAT molecules are required for normal breast
      development and involution, respectively, and may play an important role in
      breast carcinogenesis.

PMID- 11250698
TI  - Transforming growth factor-beta and breast cancer: Mammary gland development.
AB  - Transforming growth factor (TGF)-beta1 is a pluripotent cytokine that profoundly
      inhibits epithelial proliferation, induces apoptosis, and influences
      morphogenesis by mediating extracellular matrix deposition and remodeling. The
      physiologic roles of the action of TGF-beta in mammary gland, indeed in most
      tissues, are poorly understood. In order to understand the actions of TGF-beta,
      we need to take into account the complexity of its effects on different cell
      types and the influence of context on cellular responses. This task is further
      compounded by multiple mechanisms for regulating TGF-beta transcription,
      translation, and activity. One of the most significant factors that obscures the
      action of TGF-beta is that it is secreted as a stable latent complex, which
      consists of the 24-kDa cytokine and the 80-kDa dimer of its prepro region, called
      latency-associated peptide. Latency imposes a critical restraint on TGF-beta
      activity that is often overlooked. The extracellular process known as activation,
      in which TGF-beta is released from the latent complex, is emphasized in the
      present discussion of the role of TGF-beta in mammary gland development.
      Definition of the spatial and temporal patterns of latent TGF-beta activation in
      situ is essential for understanding the specific roles that TGF-beta plays during
      mammary gland development, proliferation, and morphogenesis.

PMID- 11250699
TI  - Transforming growth factor-beta and breast cancer: Lessons learned from
      genetically altered mouse models.
AB  - Transforming growth factor (TGF)-betas are plausible candidate tumor suppressors
      in the breast. They also have oncogenic activities under certain circumstances,
      however. Genetically altered mouse models provide powerful tools to analyze the
      complexities of TGF-beta action in the context of the whole animal.
      Overexpression of TGF-beta can suppress tumorigenesis in the mammary gland,
      raising the possibility that use of pharmacologic agents to enhance TGF-beta
      function locally might be an effective method for the chemoprevention of breast
      cancer. Conversely, loss of TGF-beta response increases spontaneous and induced
      tumorigenesis in the mammary gland. This confirms that endogenous TGF-betas have
      tumor suppressor activity in the mammary gland, and suggests that the loss of TGF
      beta receptors seen in some human breast hyperplasias may play a causal role in
      tumor development.

PMID- 11250700
TI  - Transforming growth factor-beta and breast cancer: Transforming growth factor
      beta/SMAD signaling defects and cancer.
AB  - Transforming growth factor-beta (TGF-beta) is a tumor suppressor, the function of
      which is compromised in many types of human cancer, including breast cancer. The
      tumor suppressive effects of TGF-beta are caused by potent inhibition of cell
      proliferation due to cell cycle arrest in the G1 phase. Such antiproliferative
      responses are mediated by a signaling system that includes two types of cell
      surface receptors and intracellular signal transducers, the SMAD proteins.
      Different molecular mechanisms can lead to loss of antiproliferative TGF-beta
      responses in tumor cells, including mutations in components of the signaling
      system and inhibition of the SMAD signaling pathway by aberrant activities of
      various regulatory molecules. Some of these mechanisms will be discussed, with
      emphasis on their potential involvement in breast tumorigenesis.

PMID- 11250701
TI  - Transforming growth factor-beta and breast cancer: Cell cycle arrest by
      transforming growth factor-beta and its disruption in cancer.
AB  - Altered responsiveness to extracellular signals and cell cycle dysregulation are
      hallmarks of cancer. The cell cycle is governed by cyclin-dependent kinases
      (cdks) that integrate mitogenic and growth inhibitory signals. Transforming
      growth factor (TGF)-beta mediates G1 cell cycle arrest by inducing or activating
      cdk inhibitors, and by inhibiting factors required for cdk activation. Mechanisms
      that lead to cell cycle arrest by TGF-beta are reviewed. Loss of growth
      inhibition by TGF-beta occurs early in breast cell transformation, and may
      contribute to breast cancer progression. Dysregulation of cell cycle effectors at
      many different levels may contribute to loss of G1 arrest by TGF-beta.
      Elucidation of these pathways in breast cancer may ultimately lead to novel and
      more effective treatments for this disease.

PMID- 11250703
TI  - Linear and cooperative signaling: roles for Stat proteins in the regulation of
      cell survival and apoptosis in the mammary epithelium.
AB  - The mammary epithelium undergoes cyclical periods of cellular proliferation,
      differentiation and regression. These processes are under the control of the
      hormones secreted during pregnancy, lactation and involution. Signaling pathways
      have been identified that connect the hormonal stimuli with the transcription of
      genes responsible for the determination of the cellular fate. The kinetics of
      induction and deinduction have suggested that cytokine-activated Stat proteins
      play a crucial role. Stat5 is strongly activated towards the end of pregnancy,
      persists in an activated state during pregnancy and is rapidly inactivated after
      cessation of suckling. Stat3 activation is hardly detectable during lactation,
      but is strongly induced at the onset of involution. The phenotypes of mice in
      which these genes have been inactivated through homologous recombination
      corroborate some of the functional assignments deducted from the activation
      pattern. Stat3 activation seems to be a driving force in the induction of
      apoptosis early in the involution period.

PMID- 11250702
TI  - Transforming growth factor-beta and breast cancer: Tumor promoting effects of
      transforming growth factor-beta.
AB  - The transforming growth factor (TGF)-betas are potent growth inhibitors of normal
      epithelial cells. In established tumor cell systems, however, the preponderant
      experimental evidence suggests that TGF-betas can foster tumor-host interactions
      that indirectly support the viability and/or progression of cancer cells. The
      timing of this 'TGF-beta switch' during the progressive transformation of
      epithelial cells is not clear. More recent evidence also suggests that autocrine
      TGF-beta signaling is operative in some tumor cells, and can also contribute to
      tumor invasiveness and metastases independent of an effect on nontumor cells. The
      dissociation of antiproliferative and matrix associated effects of autocrine TGF
      beta signaling at a transcriptional level provides for a mechanism(s) by which
      cancer cells can selectively use this signaling pathway for tumor progression.
      Data in support of the cellular and molecular mechanisms by which TGF-beta
      signaling can accelerate the natural history of tumors will be reviewed in this
      section.

PMID- 11250704
TI  - Tyrosine kinase signalling in breast cancer.
AB  - Cells are continuously exposed to diverse stimuli ranging from soluble endocrine
      and paracrine factors to signalling molecules on neighbouring cells. Receptors of
      the tyrosine kinase family play an important role in the integration and
      interpretation of these external stimuli, allowing a cell to respond
      appropriately to its environment. The activation of receptor tyrosine kinases
      (RTKs) is tightly controlled, allowing a normal cell to correctly integrate its
      external environment with internal signal transduction pathways. In contrast, due
      to numerous molecular alterations arising during the course of malignancy, a
      tumour is characterized by an abnormal response to its environment, which allows
      cancer cells to evade the normal mechanisms controlling cellular proliferation.
      Alterations in the expression of various RTKs, in their activation, and in the
      signalling molecules lying downstream of the receptors play important roles in
      the development of cancer. This topic is the major focus of the thematic review
      section of this issue of Breast Cancer Research.

PMID- 11250705
TI  - Homeobox genes in mammary gland development and neoplasia.
AB  - Both normal development and neoplastic progression involve cellular transitions
      from one physiological state to another. Whereas much is being discovered about
      signal transduction networks involved in regulating these transitions, little
      progress has been made in identifying the higher order genetic determinants that
      establish and maintain mammary cell identity and dictate cell type-specific
      responses to mammotropic signals. Homeobox genes are a large superfamily of genes
      whose members function in establishing and maintaining cell fate and cell
      identity throughout embryonic development. Recent genetic and expression analyses
      strongly suggest that homeobox genes may perform similar functions at specific
      developmental transition points in the mammary gland. These analyses also suggest
      that homeobox genes may play a contributory or causal role in breast cancer.

PMID- 11250706
TI  - Tyrosine kinase signalling in breast cancer: insulin-like growth factors and
      their receptors in breast cancer.
AB  - The insulin-like growth factor (IGF) system exerts pleiotropic effects on
      mammalian cells. This review focuses on type I IGF receptor (IGF1R)-mediated
      signal transduction and its relevance in breast cancer. Upon activation by the
      IGFs, IGF1R, a transmembrane tyrosine kinase receptor, undergoes
      autophosphorylation, and then binds and phosphorylates additional signaling
      molecules. These intermediates initiate a series of downstream signaling events
      that are involved in multiple physiologic processes for cells. Recent data
      demonstrate that the IGF receptor system actively interacts with the estrogen
      receptor and integrin receptor systems. Cross-talk among these pathways regulates
      breast cancer proliferation, protection from cell death, and metastasis. Better
      understanding of IGF biochemical signaling pathways is of utmost importance for
      developing therapies for breast cancer.

PMID- 11250707
TI  - Tyrosine kinase signalling in breast cancer: ErbB family receptor tyrosine
      kinases.
AB  - ERBB family receptor tyrosine kinases are overexpressed in a significant subset
      of breast cancers. One of these receptors, HER2/neu, or ErbB-2, is the target for
      a new rational therapeutic antibody, Herceptin. Other inhibitors that target this
      receptor, and another family member, the epidermal growth factor (EGF) receptor,
      are moving into clinical trials. Both of these receptors are sometimes
      overexpressed in breast cancer, and still subject to regulation by hormones and
      other physiological regulators. Optimal use of therapeutics targeting these
      receptors will require consideration of the several modes of regulation of these
      receptors and their interactions with steroid receptors.

PMID- 11250708
TI  - Tyrosine kinase signalling in breast cancer. Epidermal growth factor receptor:
      convergence point for signal integration and diversification.
AB  - Cross-communication between different signalling systems is critical for the
      integration of multiple and changing environmental influences on individual
      cells. The epidermal growth factor receptor (EGFR) has been identified as a key
      element in the complex signalling network that is utilized by various classes of
      cell-surface receptors. This nonclassical mode of signalling system cross-talk,
      in distinction to receptor activation induced by cognate ligands, has been termed
      'signal transactivation'. With the EGFR as the convergence point and distribution
      focus, this scenario may involve signals emitted by other members of the tyrosine
      kinase family, cytokine receptors, ion channels, G-protein-coupled receptors and
      integrins.

PMID- 11250709
TI  - Tyrosine kinase signalling in breast cancer: fibroblast growth factors and their
      receptors.
AB  - The fibroblast growth factors [Fgfs (murine), FGFs (human)] constitute a large
      family of ligands that signal through a class of cell-surface tyrosine kinase
      receptors. Fgf signalling has been associated in vitro with cellular
      differentiation as well as mitogenic and motogenic responses. In vivo, Fgfs are
      critical for animal development, and some have potent angiogenic properties.
      Several Fgfs have been identified as oncogenes in murine mammary cancer, where
      their deregulation is associated with proviral insertions of the mouse mammary
      tumour virus (MMTV). Thus, in some mammary tumours of MMTV-infected mouse
      strains, integration of viral genomic DNA into the somatic DNA of mammary
      epithelial cells was found to have caused the inappropriate expression of members
      of this family of growth factors. Although examination of human breast cancers
      has shown an altered expression of FGFs or of their receptors in some tumours,
      their role in the causation of breast disease is unclear and remains
      controversial.

PMID- 11250710
TI  - Tyrosine kinase signalling in breast cancer: modulation of tyrosine kinase
      signalling in human breast cancer through altered expression of signalling
      intermediates.
AB  - The past decade has seen the definition of key signalling pathways downstream of
      receptor tyrosine kinases (RTKs) in terms of their components and the protein
      protein interactions that facilitate signal transduction. Given the strong
      evidence that links signalling by certain families of RTKs to the progression of
      breast cancer, it is not surprising that the expression profile of key downstream
      signalling intermediates in this disease has also come under scrutiny,
      particularly because some exhibit transforming potential or amplify mitogenic
      signalling pathways when they are overexpressed. Reflecting the diverse cellular
      processes regulated by RTKs, it is now clear that altered expression of such
      signalling proteins in breast cancer may influence not only cellular
      proliferation (eg Grb2) but also the invasive properties of the cancer cells (eg
      EMS1/cortactin).

PMID- 11250713
TI  - Utilization of human tissue in breast cancer research.
AB  - The use of human tissue, and material derived from such tissue, for research
      purposes is currently the subject of much debate. This debate needs to address
      several issues, including: the principle of abandonment; the distinction between
      identified and unidentified specimens; general versus specific informed consent;
      and, with the improvement in biotechnology and medical informatics, the design
      and security of research databases. The outcome of this debate will shape the way
      in which research studies using human biological materials are designed and
      executed.

PMID- 11250712
TI  - Tyrosine kinase signalling in breast cancer: tyrosine kinase-mediated signal
      transduction in transgenic mouse models of human breast cancer.
AB  - The ability of growth factors and their cognate receptors to induce mammary
      epithelial proliferation and differentiation is dependent on their ability to
      activate a number of specific signal transduction pathways. Aberrant expression
      of specific receptor tyrosine kinases (RTKs) has been implicated in the genesis
      of a significant proportion of sporadic human breast cancers. Indeed, mammary
      epithelial expression of activated RTKs such as ErbB2/neu in transgenic mice has
      resulted in the efficient induction of metastatic mammary tumours. Although it is
      clear from these studies that activation these growth factor receptor signalling
      cascades are directly involved in mammary tumour progression, the precise
      interaction of each of these signalling pathways in mammary tumourigenesis and
      metastasis remains to be elucidated. The present review focuses on the role of
      several specific signalling pathways that have been implicated as important
      components in RTK-mediated signal transduction. In particular, it focuses on two
      well characterized transgenic breast cancer models that carry the polyomavirus
      middle T(PyV mT) and neu oncogenes.

PMID- 11250711
TI  - Tyrosine kinase signalling in breast cancer: epidermal growth factor receptor and
      c-Src interactions in breast cancer.
AB  - Both the non-receptor tyrosine kinase, c-Src, and members of the epidermal growth
      factor (EGF) receptor family are overexpressed in high percentages of human
      breast cancers. Because these molecules are plasma membrane-associated and
      involved in mitogenesis, it has been speculated that they function in concert
      with one another to promote breast cancer development and progression. Evidence
      to date supports a model wherein c-Src potentiates the survival, proliferation
      and tumorigenesis of EGF receptor family members, in part by associating with
      them. Phosphorylation of the EGF receptor by c-SRC is also critical for mitogenic
      signaling initiated by the EGF receptor itself, as well as by several G-protein
      coupled receptors (GPCRs), a cytokine receptor, and the estrogen receptor. Thus,
      c-Src appears to have pleiotropic effects on cancer cells by modulating the
      action of multiple growth-promoting receptors.

PMID- 11250714
TI  - New hurdles for translational research.
AB  - New guidelines for the collection and use of human tissues for research will
      impose new requirements on researchers to seek ethical approval and patient
      consent. This extends to the use of surplus tissue, such as breast cancer
      excision biopsies, which, until recently, have been regarded as having been
      'abandoned' by the patient. This article argues that some of these new
      constraints provide hurdles to translational research that are unnecessary for
      patient protection. This is particularly significant when emerging technologies
      are expected to elicit major advances in clinical cancer research.

PMID- 11250715
TI  - Acetyltransferases and tumour suppression.
AB  - The acetyltransferase p300 was first identified associated with the adenoviral
      transforming protein E1A, suggesting a potential role for p300 in the regulation
      of cell proliferation. Direct evidence demonstrating a role for p300 in human
      tumours was lacking until the recently publication by Gayther et al, which
      strongly supports a role for p300 as a tumour suppressor. The authors identify
      truncating mutations associated with the loss or mutation of the second allele in
      both tumour samples and cell lines, suggesting that loss of p300 may play a role
      in the development of a subset of human cancers.

PMID- 11250716
TI  - Mammographic screening and mammographic patterns.
AB  - Mammography is an effective screening modality for the early detection of breast
      cancer. The reduction in breast cancer mortality is greater for women aged over
      50 at screening than for women aged under 50. Mammography can also contribute to
      an understanding of the biology of breast cancer. Screening trials provide good
      evidence for the dedifferentiation of a cancer as it develops over time, and the
      age dependency of this dedifferentiation explains much of the age difference in
      the effectiveness of screening. Mammographic density is an important predictor of
      future breast cancer risk, and has potential as an early endpoint in breast
      cancer prevention trials. Mammographic density is also an important determinant
      of mammographic screening sensitivity.

PMID- 11250717
TI  - Metalloproteinases: role in breast carcinogenesis, invasion and metastasis.
AB  - The matrix metalloproteinases (MMPs) are a family of zinc-dependent
      endopeptidases. Their primary function is degradation of proteins in the
      extracellular matrix. Currently, at least 19 members of this family are known to
      exist. Based on substrate specificity and domain organization, the MMPs can be
      loosely divided into four main groups: the interstitial collagenases,
      gelatinases, stromelysins and membrane-type MMPs. Recent data from model systems
      suggest that MMPs are involved in breast cancer initiation, invasion and
      metastasis. Consistent with their role in breast cancer progression, high levels
      of at least two MMPs (MMP-2 and stromelysin-3) have been found to correlate with
      poor prognosis in patients with breast cancer. Because MMPs are apparently
      involved in breast cancer initiation and dissemination, inhibition of these
      proteinases may be of value both in preventing breast cancer and in blocking
      metastasis of established tumours

PMID- 11250718
TI  - Future possibilities in the prevention of breast cancer: breast cancer prevention
      trials.
AB  - The available results from breast cancer chemoprevention trials are reviewed.
      Four trials using tamoxifen have been performed, of which three have reported
      efficacy results. A fifth trial using raloxifene has also been reported. The
      largest tamoxifen trial showed approximately 50% reduction in breast cancer
      incidence in the short term, but the two smaller trials did not find any
      reduction. Greater agreement exists for side effects; incidences of
      thromboembolic disease and endometrial cancers are raised approximately threefold
      when tamoxifen is used for 5 years. The possible reasons for the discrepancy in
      breast cancer reduction are explored. A review of trial parameters does not
      clearly explain this difference, and a meta-analysis indicates that all results
      are compatible with a 40% reduction in short-term incidence. Several important
      questions remain regarding the clinical implications of this result, including
      the effect on mortality, the appropriate risk groups for chemoprevention and the
      long-term effects on incidence. Continued follow up of these trials is crucial
      for resolving these issues.

PMID- 11250719
TI  - Future possibilities in the prevention of breast cancer: luteinizing hormone
      releasing hormone agonists.
AB  - The cyclic production of estrogen and progesterone by the premenopausal ovary
      accounts for the steep rise in breast cancer risk in premenopausal women. These
      hormones are breast cell mitogens. By reducing exposure to these ovarian
      hormones, agonists of luteinizing hormone-releasing hormone (LHRH) given to
      suppress ovarian function may prove useful in cancer prevention. To prevent
      deleterious effects of hypoestrogenemia, the addition of low-dose hormone
      replacement to the LHRH agonist appears necessary. Pilot data with such an
      approach indicates it is feasible and reduces mammographic densities.

PMID- 11250720
TI  - Future possibilities in the prevention of breast cancer: fat and fiber and breast
      cancer research.
AB  - The potential for a reduction in dietary fat or for an increase in dietary fiber
      to reduce breast cancer risk has been debated for some years. It is argued here
      that available research data, even though extensive, leave open hypotheses
      ranging from little or no potential to major public health potential for breast
      cancer prevention by means of these dietary maneuvers. Some elements of a
      research strategy for testing these and other dietary breast cancer prevention
      hypotheses are described.

PMID- 11250721
TI  - Future possibilities in the prevention of breast cancer: role of genetic
      variation in breast cancer prevention.
AB  - Risk factors for breast cancer are related to endogenous hormones and
      reproductive events. As such, traditional cancer prevention strategies are not
      easily applicable. Tamoxifen and other selective estrogen receptor modulators
      (SERMs) offer a new preventive strategy for some high-risk women, but have not
      yet been shown to be efficacious for all women. New tools to identify high-risk
      women are needed. One such tool is the development of a multigenic model of
      breast cancer susceptibility that can be used to screen women in order to
      identify those who carry a combination of alleles that puts them at significantly
      increased risk.

PMID- 11250723
TI  - Metastases: the glycan connection.
AB  - An association between protein glycosylation and tumorigenesis has been
      recognized for over 10 years. Associations linking the importance of
      glycosylation events to tumor biology, especially the progression to metastatic
      disease, have been noted over many years, Recently, a mouse model in which
      beta1,6-N-acetylglucosaminyltransferase V (a rate-limiting enzyme in the N-glycan
      pathway) has been knocked out, was used to demonstrate the importance of
      glycosylation in tumor progression. By crossing mice lacking this enzyme with a
      transgenic mouse model of metastatic breast cancer, metastatic progression of the
      disease was dramatically reduced. These experiments provide in vivo evidence for
      the role of N-linked glycosylation in metastatic breast cancer and have
      significant implications for the development of new treatment strategies.

PMID- 11250722
TI  - Future possibilities in the prevention of breast cancer: intervention strategies
      in BRCA1 and BRCA2 mutation carriers.
AB  - The development of intervention strategies for carriers of mutations in the BRCA1
      and BRCA2 genes has several considerations. The first are primary prevention and
      secondary prevention in unaffected carriers using medical/surgical or lifestyle
      strategies to prevent cancer development, or screening methods to detect cancers
      at an earlier stage. The options available are determined by the magnitude and
      age at onset, risk profile of cancer in carriers (the penetrance function of the
      gene) and the different cancer sites involved. The management of affected
      individuals who are BRCA1 and BRCA2 mutation carriers may be altered by their
      carrier status, because the tumour histology, efficacy of treatment and risk of
      subsequent cancer development is determined by the BRCA1 and BRCA2 germline
      status. Carriers of BRCA1 and BRCA2 mutations are relatively rare, so the
      strategies for management should be determined by international multicentre
      studies.

PMID- 11250724
TI  - Role of BRCA gene dysfunction in breast and ovarian cancer predisposition.
AB  - Tumor suppressor genes that perform apparently generic cellular functions
      nonetheless cause tissue-specific syndromes in the human population when they are
      mutated in the germline. The two major hereditary breast/ovarian cancer
      predisposition genes, BRCA1 and BRCA2, appear to participate in a common pathway
      that is involved in the control of homologous recombination and in the
      maintenance of genomic integrity. How might such functions translate into the
      specific suppression of cancers of the breast and ovarian epithelia? Recent
      advances in the study of BRCA1 and BRCA2, discussed herein, have provided new
      opportunities to address this question.

PMID- 11250725
TI  - Nontransgenic models of breast cancer.
AB  - Numerous models have been developed to address key elements in the biology of
      breast cancer development and progression. No model is ideal, but the most useful
      are those that reflect the natural history and histopathology of human disease,
      and allow for basic investigations into underlying cellular and molecular
      mechanisms. We describe two types of models: those that are directed toward early
      events in breast cancer development (hyperplastic alveolar nodules [HAN] murine
      model, MCF10AT human xenograft model); and those that seek to reflect the
      spectrum of metastatic disease (murine sister cell lines 67, 168, 4T07, 4T1).
      Collectively, these models provide cell lines that represent all of the
      sequential stages of progression in breast disease, which can be modified to test
      the effect of genetic changes.

PMID- 11250726
TI  - Estrogen receptor transcription and transactivation: Estrogen receptor alpha and
      estrogen receptor beta: regulation by selective estrogen receptor modulators and
      importance in breast cancer.
AB  - Estrogens display intriguing tissue-selective action that is of great biomedical
      importance in the development of optimal therapeutics for the prevention and
      treatment of breast cancer, for menopausal hormone replacement, and for fertility
      regulation. Certain compounds that act through the estrogen receptor (ER), now
      referred to as selective estrogen receptor modulators (SERMs), can demonstrate
      remarkable differences in activity in the various estrogen target tissues,
      functioning as agonists in some tissues but as antagonists in others. Recent
      advances elucidating the tripartite nature of the biochemical and molecular
      actions of estrogens provide a good basis for understanding these tissue
      selective actions. As discussed in this thematic review, the development of
      optimal SERMs should now be viewed in the context of two estrogen receptor
      subtypes, ERalpha and ERbeta, that have differing affinities and responsiveness
      to various SERMs, and differing tissue distribution and effectiveness at various
      gene regulatory sites. Cellular, biochemical, and structural approaches have also
      shown that the nature of the ligand affects the conformation assumed by the ER
      ligand complex, thereby regulating its state of phosphorylation and the
      recruitment of different coregulator proteins. Growth factors and protein kinases
      that control the phosphorylation state of the complex also regulate the
      bioactivity of the ER. These interactions and changes determine the magnitude of
      the transcriptional response and the potency of different SERMs. As these
      critical components are becoming increasingly well defined, they provide a sound
      basis for the development of novel SERMs with optimal profiles of tissue
      selectivity as medical therapeutic agents.

PMID- 11250727
TI  - Estrogen receptor transcription and transactivation: Estrogen receptor knockout
      mice: what their phenotypes reveal about mechanisms of estrogen action.
AB  - Natural, synthetic and environmental estrogens have numerous effects on the
      development and physiology of mammals. Estrogen is primarily known for its role
      in the development and functioning of the female reproductive system. However,
      roles for estrogen in male fertility, bone, the circulatory system and immune
      system have been established by clinical observations regarding sex differences
      in pathologies, as well as observations following menopause or castration. The
      primary mechanism of estrogen action is via binding and modulation of activity of
      the estrogen receptors (ERs), which are ligand-dependent nuclear transcription
      factors. ERs are found in highest levels in female tissues critical to
      reproduction, including the ovaries, uterus, cervix, mammary glands and pituitary
      gland. Since other affected tissues have extremely low levels of ER, indirect
      effects of estrogen, for example induction of pituitary hormones that affect the
      bone, have been proposed. The development of transgenic mouse models that lack
      either estrogen or ER have proven to be valuable tools in defining the mechanisms
      by which estrogen exerts its effects in various systems. The aim of this article
      is to review the mouse models with disrupted estrogen signaling and describe the
      associated phenotypes.

PMID- 11250728
TI  - Estrogen receptor transcription and transactivation: Structure-function
      relationship in DNA- and ligand-binding domains of estrogen receptors.
AB  - Estrogen receptors are members of the nuclear receptor steroid family that
      exhibit specific structural features, ligand-binding domain sequence identity and
      dimeric interactions, that single them out. The crystal structures of their DNA
      binding domains give some insight into how nuclear receptors discriminate between
      DNA response elements. The various ligand-binding domain crystal structures of
      the two known estrogen receptor isotypes (alpha and beta) allow one to interpret
      ligand specificity and reveal the interactions responsible for stabilizing the
      activation helix H12 in the agonist and antagonist positions.

PMID- 11250730
TI  - Breast cancer risk perception: what do we know and understand?
AB  - Women's perceptions of breast cancer risk are largely inaccurate and are often
      associated with high levels of anxiety about cancer. There are interesting
      cultural differences that are not well researched. Genetic risk counselling
      significantly improves accuracy of women's perceptions of risk, but not
      necessarily to the correct level. Reasons for this are unclear, but may relate to
      personal beliefs about susceptibility and to problems or variations in risk
      communication. Research into the impact of demographic and psychological factors
      on risk perception has been inconclusive. An understanding of the process of
      developing a perception of risk would help to inform risk counselling strategies.
      This is important, because knowledge of risk is needed both for appropriate
      health care decision making and to reassure women who are not at increased risk.

PMID- 11250729
TI  - Estrogen receptor transcription and transactivation: Basic aspects of estrogen
      action.
AB  - Estrogen signaling has turned out to be much more complex and exciting than
      previously thought; the paradigm shift in our understanding of estrogen action
      came in 1996, when the presence of a new estrogen receptor (ER), ERbeta, was
      reported. An intricate interplay between the classical ERalpha and the novel
      ERbeta is of paramount importance for the final biological effect of estrogen in
      different target cells.

PMID- 11250731
TI  - Computer-assisted mammographic imaging.
AB  - Computer-assisted mammography imaging comprises computer-based analysis of
      digitized images resulting in prompts aiding mammographic interpretation and
      computerized stereotactic localization devices which improve location accuracy.
      The commercial prompting systems available are designed to draw attention to
      mammographic abnormalities detected by algorithms based on symptomatic practise
      in North America. High sensitivity rates are important commercially but result in
      increased false prompt rates, which are known to distract radiologists. A
      national shortage of breast radiologists in the UK necessitates evaluation of
      such systems in a population breast screening programme to determine
      effectiveness in increasing cancer detection and feasibility of implementation.

PMID- 11250732
TI  - Molecular biology of breast cancer metastasis. 'Has it spread?': disarming one of
      the most terrifying questions.

PMID- 11250733
TI  - Molecular biology of breast cancer metastasis. Clinical implications of
      experimental studies on metastatic inefficiency.
AB  - Recent technological advances have led to an increasing ability to detect
      isolated tumour cells and groups of tumour cells in patients' blood, lymph nodes
      or bone marrow. However, the clinical significance of these cells is unclear.
      Should they be considered as evidence of metastasis, necessitating aggressive
      treatment, or are they in some cases unrelated to clinical outcome? Quantitative
      experimental studies on the basic biology of metastatic inefficiency are
      providing clues that may help in understanding the significance of these cells.
      This understanding will be of use in guiding clinical studies to assess the
      significance of isolated tumour cells and micrometastases in cancer patients.

PMID- 11250734
TI  - Molecular biology of breast cancer metastasis. Genetic regulation of human breast
      carcinoma metastasis.
AB  - The present is an overview of recent data that describes the genetic
      underpinnings of the suppression of cancer metastasis. Despite the explosion of
      new information about the genetics of cancer, only six human genes have thus far
      been shown to suppress metastasis functionally. Not all have been shown to be
      functional in breast carcinoma. Several additional genes inhibit various steps of
      the metastatic cascade, but do not necessarily block metastasis when tested using
      in vivo assays. The implications of this are discussed. Two recently discovered
      metastasis suppressor genes block proliferation of tumor cells at a secondary
      site, offering a new target for therapeutic intervention.

PMID- 11250735
TI  - Molecular biology of breast cancer metastasis. Molecular expression of vascular
      markers by aggressive breast cancer cells.
AB  - During embryogenesis, the formation of primary vascular networks occurs via the
      processes of vasculogenesis and angiogenesis. In uveal melanoma, vasculogenic
      mimicry describes the 'embryonic-like' ability of aggressive, but not
      nonaggressive, tumor cells to form networks surrounding spheroids of tumor cells
      in three-dimensional culture; these recapitulate the patterned networks seen in
      patients' aggressive tumors and correlates with poor prognosis. The molecular
      profile of these aggressive tumor cells suggests that they have a deregulated
      genotype, capable of expressing vascular phenotypes. Similarly, the embryonic
      like phenotype expressed by the aggressive human breast cancer cells is
      associated with their ability to express a variety of vascular markers. These
      studies may offer new insights for consideration in breast cancer diagnosis and
      therapeutic intervention strategies.

PMID- 11250737
TI  - Molecular biology of breast cancer metastasis. The use of mathematical models to
      determine relapse and to predict response to chemotherapy in breast cancer.
AB  - Breast cancer mortality rates have shown only modest improvement despite the
      advent of effective chemotherapeutic agents which have been administered to a
      large percentage of women with breast cancer. In an effort to improve breast
      cancer treatment strategies, a variety of mathematical models have been developed
      that describe the natural history of breast cancer and the effects of treatment
      on the cancer. These models help researchers to develop, quantify, and test
      various treatment hypotheses quickly and efficiently. The present review
      discusses several of these models, with a focus on how they have been used to
      predict the initiation time of metastatic growth, the effect of operative therapy
      on the growth of metastases, and the optimal administration strategy for
      chemotherapy.

PMID- 11250736
TI  - Molecular biology of breast cancer metastasis. Inflammatory breast cancer:
      clinical syndrome and molecular determinants.
AB  - Inflammatory breast cancer (IBC) is an aggressive form of locally advanced breast
      cancer (LABC) that effects approximately 5% of women with breast cancer annually
      in the USA. It is a clinically and pathologically distinct form of LABC that is
      particularly fast growing, invasive, and angiogenic. Nearly all women have lymph
      node involvement at the time of diagnosis, and approximately 36% have gross
      distant metastases. Despite recent advances in multimodality treatments, the
      prognosis of patients with IBC is poor, with a median disease-free survival of
      less than 2.5 years. Recent work on the genetic determinants that underlie the
      IBC phenotype has led to the identification of genes that are involved in the
      development and progression of this disease. This work has been aided by the
      establishment of primary human cell lines and animal models. These advances
      suggest novel targets for future interventions in the diagnosis and treatment of
      IBC.

PMID- 11250738
TI  - The mammary myoepithelial cell--Cinderella or ugly sister?
AB  - The breast myoepithelial cell is the Cinderella of mammary biology. Although its
      contribution to benign and some malignant pathologies is recognised, it has been
      largely neglected in molecular and biological studies. The reason for this has
      been the perception that its role in normal physiology is confined to lactation
      and the belief that most breast cancers arise from luminal epithelial cells. This
      review presents our perspective on its broader biological significance and its
      potential use as a model system for understanding breast carcinogenesis.

PMID- 11250739
TI  - Syk: a new player in the field of breast cancer.
AB  - Breast tumor development and progression are thought to occur through a complex,
      multistep process, including oncogene activation (eg HER2/neu) and mutation or
      loss of tumor suppressor genes (eg p53). Determining the function of genetic
      alterations in breast carcinoma tumorigenesis and metastasis has been the focus
      of intensive research efforts for several decades. One group of proteins that
      play a critical role in breast cancer cell signaling pathways are tyrosine
      kinases. Overexpression of the tyrosine kinase HER2/neu is observed in many human
      breast cancers and is positively correlated with enhanced tumorigenesis.
      Recently, another tyrosine kinase, Syk, has been implicated as an important
      inhibitor of breast cancer cell growth and metastasis. This recent finding was
      unexpected, since Syk function has been predominantly linked to hematopoietic
      cell signaling, and is discussed further in this commentary.

PMID- 11250740
TI  - Whither high-dose chemotherapy in breast cancer?
AB  - Four trials of high-dose chemotherapy with stem cell support in breast cancer in
      the adjuvant and metastatic settings have shown no long-term disease-free or
      overall survival gain. This relative failure of a single high-dose therapy we
      believe opens up the development of a dose-dense approach with block scheduling
      as the most promising way forward. This intensive chemotherapy can be more easily
      combined with the newer biological therapies and our prediction is that this will
      prove to be the most effective treatment in the future for women with poor risk
      breast cancer.

PMID- 11250741
TI  - BRCA1 function in T lymphocytes: a cellular specificity of a different kind.
AB  - Recent work by Mak et al demonstrates that mice carrying a T-cell-specific
      disruption of the brca1 gene display markedly impaired T-lymphocyte development
      and proliferation in the absence of any increased tendency for the formation of
      tumors. Interestingly, the extent of these defects was found to be highly
      dependent on cellular context. Contrasting the rather broad tissue expression
      pattern of brca1 against its exquisitely selective etiologic role in cancers of
      the breast and ovary, many of us are left to ponder--where is the specificity?

PMID- 11250742
TI  - Recent advances in imaging endogenous or transferred gene expression utilizing
      radionuclide technologies in living subjects: applications to breast cancer.
AB  - A variety of imaging technologies is being investigated as tools for studying
      gene expression in living subjects. Two technologies that use radiolabeled
      isotopes are single photon emission computed tomography (SPECT) and positron
      emission tomography (PET). A relatively high sensitivity, a full quantitative
      tomographic capability, and the ability to extend small animal imaging assays
      directly into human applications characterize radionuclide approaches. Various
      radiolabeled probes (tracers) can be synthesized to target specific molecules
      present in breast cancer cells. These include antibodies or ligands to target
      cell surface receptors, substrates for intracellular enzymes, antisense
      oligodeoxynucleotide probes for targeting mRNA, probes for targeting
      intracellular receptors, and probes for genes transferred into the cell. We
      briefly discuss each of these imaging approaches and focus in detail on imaging
      reporter genes. In a PET reporter gene system for in vivo reporter gene imaging,
      the protein products of the reporter genes sequester positron emitting reporter
      probes. PET subsequently measures the PET reporter gene dependent sequestration
      of the PET reporter probe in living animals. We describe and review reporter gene
      approaches using the herpes simplex type 1 virus thymidine kinase and the
      dopamine type 2 receptor genes. Application of the reporter gene approach to
      animal models for breast cancer is discussed. Prospects for future applications
      of the transgene imaging technology in human gene therapy are also discussed.
      Both SPECT and PET provide unique opportunities to study animal models of breast
      cancer with direct application to human imaging. Continued development of new
      technology, probes and assays should help in the better understanding of basic
      breast cancer biology and in the improved management of breast cancer patients.

PMID- 11250743
TI  - Imaging biochemistry: applications to breast cancer.
AB  - The use of magnetic resonance spectroscopy (MRS) to investigate breast tumour
      biochemistry in vivo is reviewed. To this end, results obtained both from
      patients in vivo and from tumour extracts and model systems are discussed. An
      association has been observed between transformation and an increase in
      phosphomonoesters (PMEs) detected in the 31P MRS spectrum, as well as an increase
      in choline-containing metabolites detected in the 1H spectrum. A decrease in PME
      content after treatment is associated with response to treatment as assessed by
      tumour volume. Experiments in model systems aimed at understanding the underlying
      biochemical processes are presented, as well as data indicating the usefulness of
      MRS in monitoring the uptake and metabolism of some chemotherapeutic agents.

PMID- 11250744
TI  - Probing physiology and molecular function using optical imaging: applications to
      breast cancer.
AB  - The present review addresses the capacity of optical imaging to resolve
      functional and molecular characteristics of breast cancer. We focus on recent
      developments in optical imaging that allow three-dimensional reconstruction of
      optical signatures in the human breast using diffuse optical tomography (DOT).
      These technologic advances allow the noninvasive, in vivo imaging and
      quantification of oxygenated and deoxygenated hemoglobin and of contrast agents
      that target the physiologic and molecular functions of tumors. Hence, malignancy
      differentiation can be based on a novel set of functional features that are
      complementary to current radiologic imaging methods. These features could enhance
      diagnostic accuracy, lower the current state-of-the-art detection limits, and
      play a vital role in therapeutic strategy and monitoring.

PMID- 11250745
TI  - VIII International Congress of the Metastasis Research Society.

PMID- 11250746
TI  - Comparison of written reports of mammography, sonography and magnetic resonance
      mammography for preoperative evaluation of breast lesions, with special emphasis
      on magnetic resonance mammography.
AB  - Patients with abnormal breast findings (n = 413) were examined by mammography,
      sonography and magnetic resonance (MR) mammography; 185 invasive cancers, 38
      carcinoma in situ and 254 benign tumours were confirmed histologically.
      Sensitivity for mammography was 83.7%, for sonography it was 89.1% and for MR
      mammography it was 94.6% for invasive cancers. In 42 patients with multifocal
      invasive cancers, multifocality had been detected by mammography and sonography
      in 26.2%, and by MR mammography in 66.7%. In nine patients with multicentric
      cancers, detection rates were 55.5, 55.5 and 88.8%, respectively. Carcinoma in
      situ was diagnosed by mammography in 78.9% and by MR mammography in 68.4% of
      patients. Combination of all three diagnostic methods lead to the best results
      for detection of invasive cancer and multifocal disease. However, sensitivity of
      mammography and sonography combined was identical to that of MR mammography
      (i.e., 94.6%).

PMID- 11250747
TI  - BRCA1 and BRCA2 protein expressions in an ovotestis of a 46, XX true
      hermaphrodite.
AB  - BRCA1 and BRCA2 breast cancer susceptibility genes encode proteins, the normal
      cellular functions of which are complex and multiple, and germ-line mutations in
      individuals predispose both to breast and to ovarian cancer. There is
      nevertheless substantial evidence linking BRCA1 and BRCA2 to homologous
      recombination and DNA repair, to transcriptional control and to tissue
      proliferation. There is controversy regarding the localization of BRCA1 and BRCA2
      proteins to either nucleus or cytoplasm and whether the expression is present in
      premeiotic germ cells or can still be expressed in mitotic spermatogonia. We
      report herein an immunohistochemical study of BRCA1 and BRCA2 distribution in a
      rather unusual tissue (an ovotestis), which addresses this issue.

PMID- 11250748
TI  - Transforming growth factors-beta are not good biomarkers of chemopreventive
      efficacy in a preclinical breast cancer model system.
AB  - Using a carcinogen-initiated rat model of mammary tumorigenesis, we tested the
      hypothesis that transforming growth factor (TGF)-betas are useful biomarkers of
      chemopreventive efficacy in the breast. The chemopreventive agents tested were
      tamoxifen and the retinoids 9-cis-retinoic acid (9cRA) and N-(4
      hydroxyphenyl)retinamide (4-HPR), because both antiestrogens and retinoids have
      previously been shown to upregulate TGF-betas in vitro. Despite demonstrable
      chemopreventive efficacy in this model, none of these agents, alone or in
      combination, had any significant impact on the expression of TGF-betas in the
      mammary ductal epithelium or periductal stroma as determined by
      immunohistochemistry. These data suggest that TGF-betas are not likely to be
      useful biomarkers of chemopreventive efficacy in a clinical setting.

PMID- 11250749
TI  - Molecular profiling of breast cancer: portraits but not physiognomy.
AB  - Breast cancers differ in response to treatment and may have a divergent clinical
      course despite having a similar histopathological appearance. New technology
      using DNA microarrays provides a systematic method to identify key markers for
      prognosis and treatment response by profiling thousands of genes expressed in a
      single cancer. Microarray profiling of 38 invasive breast cancers now confirms
      striking molecular differences between ductal carcinoma specimens and suggests a
      new classification for oestrogen-receptor negative breast cancer. Future
      approaches will need to include methods for high-throughput clinical validation
      and the ability to analyze microscopic samples.

PMID- 11250750
TI  - From Bittner to Barr: a viral, diet and hormone breast cancer aetiology
      hypothesis.
AB  - It is hypothesized that the human homologue of the mouse mammary tumour virus
      (HHMMTV) and other viruses, such as human papillomavirus (HPV) and Epstein-Barr
      virus (EBV), act as cofactors with diet, oestrogens and other hormones in the
      initiation and promotion of some types of breast cancer in genetically
      susceptible women. It is further hypothesized that diet influences the risk of
      breast cancer, through its influence on oestrogen metabolism and that of other
      hormones, in combination with genetic and infectious agents.

PMID- 11250751
TI  - Monoclonal antibodies targeting cancer: 'magic bullets' or just the trigger?
AB  - The first monoclonal antibodies (mAbs) approved for cancer therapy are now in
      Phase II and III trials, but the critical mechanism(s) determining efficacy and
      response in patients are still largely undefined. Both the direct antigen-binding
      (Fab) and constant (Fc) regions of mAbs can contribute to their biological
      activity. However, Clynes et al (Nat Med 2000, 6:443) recently suggested that the
      latter (at least in experimental models) might be the dominant component in vivo,
      triggering host responses to destroy cancer cells. Those workers showed that in
      mice lacking 'activation' Fc receptors (Fc(gamma)RI and Fc(gamma)RIII), anti
      tumour effects of certain mAbs were significantly reduced. In contrast, mice
      deficient in the 'inhibitory' receptor Fc(gamma)RIIB responded with tumour growth
      inhibition and enhanced antibody-dependent cellular cytotoxicity (ADCC). These
      observations suggest that mAbs might be engineered for preferential binding to
      Fc(gamma)RIII to maximise therapeutic benefit. However, further work is needed to
      establish a definitive cause-effect relationship in experimental models that are
      more clinically relevant, to determine whether human Fc(gamma)R isoforms behave
      in a similar fashion, and to confirm that therapeutic mAbs and host cells can
      adequately access solid tumour deposits to mediate effective ADCC in situ.
      Finally, the 'cost-benefit' ratio of such modified macromolecules will need to be
      measured against mini-mAb constructs, antisense oligonucleotides, peptidomimetics
      and emerging drugs capable of inhibiting key tumour cell signalling pathways.

PMID- 11250752
TI  - The cyclin dependent kinase inhibitor p27 and its prognostic role in breast
      cancer.
AB  - p27 is an inhibitor of cyclin dependent kinase involved in the regulation of the
      cell cycle. In this commentary we discuss the current knowledge on p27 in breast
      cancer and its significance in predicting the outcome. p27 protein levels are
      high in most cases of breast carcinomas, are correlated with the levels of cyclin
      D1 and estrogen receptor, and could be a useful predictor of survival, because
      they are low in aggressive carcinomas. Immunodetection of p27 in breast tumors
      could be useful in the assessment of prognosis, especially in those cases in
      which the commonly used parameters are insufficient, and might ultimately
      influence the therapy of this disease.

PMID- 11250753
TI  - Challenges to the development of antigen-specific breast cancer vaccines.
AB  - Continued progress in the development of antigen-specific breast cancer vaccines
      depends on the identification of appropriate target antigens, the establishment
      of effective immunization strategies, and the ability to circumvent immune escape
      mechanisms. Methods such as T cell epitope cloning and serological expression
      cloning (SEREX) have led to the identification of a number target antigens
      expressed in breast cancer. Improved immunization strategies, such as using
      dendritic cells to present tumor-associated antigens to T lymphocytes, have been
      shown to induce antigen-specific T cell responses in vivo and, in some cases,
      objective clinical responses. An outcome of successful tumor immunity is the
      evolution of antigen-loss tumor variants. The development of a polyvalent breast
      cancer vaccine, directed against a panel of tumor-associated antigens, may
      counteract this form of immune escape.

PMID- 11250754
TI  - Breast cancer chemoprevention: beyond tamoxifen.
AB  - A large number of new potential chemoprevention agents are available that target
      molecular abnormalities found in estrogen receptor (ER)-negative and/or ER
      positive precancerous breast tissue and have side effect profiles that differ
      from tamoxifen. Classes of agents currently undergoing evaluation in clinical
      prevention trials or those for which testing is planned in the near future
      include new selective ER modulators, aromatase inactivators/inhibitors,
      gonadotrophin-releasing hormone agonists, monoterpenes, isoflavones, retinoids,
      rexinoids, vitamin D derivatives, and inhibitors of tyrosine kinase,
      cyclooxygenase-2, and polyamine synthesis. New clinical testing models will use
      morphological and molecular biomarkers to select candidates at highest short-term
      risk, to predict the response to a particular class of agent, and to assess the
      response in phase II prevention trials. If validated, morphological and molecular
      markers could eventually replace cancer incidence as an indicator of efficacy in
      future phase III trials.

PMID- 11250755
TI  - Clinical aspects of sentinel node biopsy.
AB  - Sentinel lymph node (SLN) biopsy requires validation by a backup axillary
      dissection in a defined series of cases before becoming standard practice, to
      establish individual and institutional success rates and the frequency of false
      negative results. At least 90% success in finding the SLN with no more than 5-10%
      false negative results is a reasonable goal for surgeons and institutions
      learning the technique. A combination of isotope and dye to map the SLN is
      probably superior to either method used alone, yet a wide variety of technical
      variations in the procedure have produced a striking similarity of results. Most
      breast cancer patients are suitable for SLN biopsy, and the large majority
      reported to date has had clinical stage T1-2N0 invasive breast cancers. SLN
      biopsy will play a growing role in patients having prophylactic mastectomy, and
      in those with 'high-risk' duct carcinoma in situ, microinvasive cancers, T3
      disease, and neoadjuvant chemotherapy. SLN biopsy for the first time makes
      enhanced pathologic analysis of lymph nodes logistically feasible, at once
      allowing greater staging accuracy and less morbidity than standard methods.
      Retrospective data suggest that micrometastases identified in this way are
      prognostically significant, and prospective clinical trials now accruing promise
      a definitive answer to this issue.

PMID- 11250757
TI  - Pathological validation and significance of micrometastasis in sentinel nodes in
      primary breast cancer.
AB  - In embracing a multidisciplinary approach to the management of patients with
      sentinel node biopsy in breast cancer, the pathologist task is to screen sentinel
      nodes for possible metastasis. The consequences of missing sentinel node
      micrometastasis can directly influence treatment strategies, and this screening
      therefore has to be performed with more attention than usual. There is presently
      great diversity in the histopathological work-up of sentinel nodes, with many
      centres employing additional techniques such as immunohistochemistry, reverse
      transcription polymerase chain reaction or flow cytometry in addition to routine
      haematoxylin and eosin staining. In this review, we address the pathological
      validation and significance of micrometastasis in sentinel node biopsy in primary
      breast cancer.

PMID- 11250756
TI  - History of sentinel node and validation of the technique.
AB  - Sentinel node biopsy is a minimally invasive technique to select patients with
      occult lymph node metastases who may benefit from further regional or systemic
      therapy. The sentinel node is the first lymph node reached by metastasising cells
      from a primary tumour. Attempts to remove this node with a procedure based on
      standard anatomical patterns did not become popular. The development of the
      dynamic technique of intraoperative lymphatic mapping in the 1990s resulted in
      general acceptance of the sentinel node concept. This hypothesis of sequential
      tumour dissemination seems to be valid according to numerous studies of sentinel
      node biopsy with confirmatory regional lymph node dissection. This report
      describes the history and the validation of the technique, with particular
      reference to breast cancer.

PMID- 11250758
TI  - Hormones and cancer 2000.

PMID- 11250760
TI  - An investigation of soy intake and mammographic characteristics in Hawaii.
AB  - This cross-sectional investigation in Hawaii explored the relation between soy
      foods and mammographic characteristics using two food frequency questionnaires
      and a computer-assisted density assessment method. Japanese and Chinese women
      reported significantly greater soy food intake than Caucasian women. Whereas soy
      intake and the size of the dense areas were not related, soy intake and percent
      mammographic densities were positively associated. The size of the entire breast
      and the nondense area (ie the fatty part of the breast) were inversely related to
      soy intake. These results suggest the hypothesis that soy foods by themselves or
      as part of an Asian dietary pattern may affect the growth of the female breast
      before adulthood, but the possible mechanisms of action have to be explored in
      future studies.

PMID- 11250761
TI  - Finasteride cream in hirsutism.
AB  - OBJECTIVE: To determine, in a preliminary study, whether women with hirsutism
      attributable to various causes would benefit from treatment with finasteride
      cream. METHODS: Finasteride cream (0.25%) and placebo cream were administered to
      eight women with various degrees of facial hirsutism. The two creams were used on
      opposite sides of the face in an area of excessive hair growth. The side chosen
      for the finasteride cream versus placebo was randomized and blinded. In a 1 cm2
      area on each side of the face, hair counts were done every 2 months throughout
      the 6-month study period. Hair thickness was also measured. RESULTS: Hair
      follicles respond to testosterone by the conversion of this androgen to
      dihydrotestosterone through the action of 5a-reductase. Finasteride partially
      blocks this enzyme. Because of the easy solubility of this medication through the
      skin, a cream applied to the area of hair growth would be expected to decrease
      hirsutism locally. After a 6-month period, mean hair counts decreased
      significantly from 27.5 to 15.5 (P<0.05) in the finasteride-treated sites but
      showed no significant change from baseline in the placebo-applied sites.
      Moreover, the mean thickness of the measured hairs (in hundredths of millimeters)
      was significantly different between the placebo and finasteride-treated sites
      (4.33 versus 3.11, respectively; P<0.001). CONCLUSION: In this study of women
      with facial hirsutism, topically applied finasteride significantly decreased hair
      growth and thickness, and no adverse effects were noted.

PMID- 11250762
TI  - Corticosteroid-induced inhibition of adrenal androgen production in selected
      patients with prostate cancer.
AB  - OBJECTIVE: To determine the effect of administration of corticosteroids on
      adrenal androgen production and the serologic markers of prostate cancer.
      METHODS: Six patients with prostate cancer who had a serum testosterone
      concentration that exceeded 20 ng/dL despite treatment with medical or surgical
      castration were treated with dexamethasone. All patients were asymptomatic, but
      four were demonstrating progressive increases in serum prostate-specific antigen
      (PSA) concentrations. Dexamethasone, 1 mg at bedtime, was given initially and
      then increased to 1 mg twice daily if serum testosterone concentrations remained
      > or =10 ng/dL. The effect of treatment on PSA concentration was monitored.
      RESULTS: The mean testosterone concentration (and standard error of the mean) was
      47.5 +/- 7.9 ng/dL before administration of dexamethasone; this decreased to 5.2
      +/- 3.0 ng/dL during therapy (P = 0.002). The effect was rapid (overnight) and
      sustainable (for 6 months). Although the duration of follow-up is limited, PSA
      concentrations generally stabilized (23.5 +/- 6.1 ng/mL at baseline in comparison
      with 15.6 +/- 1.1 ng/mL approximately 2 months after initiation of dexamethasone
      therapy; P = 0.24). Two patients required 1 mg of dexamethasone twice daily to
      suppress serum testosterone levels to <10 ng/dL. CONCLUSION: Administration of
      corticosteroids in a manner opposing the normal circadian glucocorticoid
      production effectively and rapidly decreases adrenal androgen production in
      patients with prostate cancer treated with orchiectomy or luteinizing hormone
      releasing hormone agonists. This reduction of androgen production was generally
      associated with a decrease or stabilization of PSA concentrations in all patients
      with increased PSA levels. Overnight dexamethasone suppression testing is useful
      in determining the minimal effective dose.

PMID- 11250763
TI  - Serum thyrotropin in primary hypothyroidism: a reliable and accurate predictor of
      optimal daily levothyroxine dose.
AB  - OBJECTIVE: To assess the reliability and accuracy of the predicted optimal daily
      levothyroxine (LT4) dose based on pretreatment serum thyrotropin (thyroid
      stimulating hormone or TSH) level in primary hypothyroidism. METHODS: We examined
      the relationships between the actual daily LT4 dose required to attain and
      maintain normal serum TSH concentration and the calculated daily LT4 dose, based
      on previously established correlations with pretreatment serum TSH
      concentrations, in 108 consecutive patients with primary hypothyroidism treated
      in an endocrinology clinic during an 18-month period. RESULTS: Highly significant
      correlations were noted between the optimal daily LT4 dose and the calculated
      dose based on either logarithmic regression (r = 0.86; P<0.00001) or linear
      regression (r = 0.83; P<0.00001). Moreover, the actual mean daily LT4 dose (133
      +/- 4 mg) approximated the mean doses predicted by both regression analyses (129
      +/- 5 mg and 126 +/- 5 mg, respectively) and was identical in many of the study
      subjects. CONCLUSION: The predicted optimal daily LT4 dose based on pretreatment
      serum TSH level provides a reliable and accurate approximation of the final
      optimal LT4 dose in patients with primary hypothyroidism and therefore may be a
      more convenient and cost-effective therapeutic approach than the current
      traditional clinical practice.

PMID- 11250759
TI  - Mechanisms of suberoylanilide hydroxamic acid inhibition of mammary cell growth.
AB  - The mechanism of suberoylanilide hydroxamic acid in cell growth inhibition
      involved induction of pRb-2/p130 interaction and nuclear translocation with E2F
      4, followed by significant repression in E2F-1 and PCNA nuclear levels, which led
      to inhibition in DNA synthesis in mammary epithelial cell lines.

PMID- 11250764
TI  - Multiple endocrine neoplasia type iia: report of a family with a study of three
      generations in qatar.
AB  - OBJECTIVE: To study the pattern of multiple endocrine neoplasia type IIA (MEN
      IIA) and describe the clinical features and results of genetic testing and
      treatment in 21 members of the first reported family with MEN IIA in Qatar.
      METHODS: After identification of the proband, we screened all her family members
      (21 members) with genetic testing for the RET proto-oncogene mutation. Those
      subjects with the mutation were further assessed for pheochromocytoma by
      measurement of the 24-hour urinary vanillylmandelic acid, metanephrines, and
      catecholamines, and those with high levels underwent a metaiodobenzylguanidine
      scan and adrenalectomy. The serum calcium was measured in a effort to detect
      hyperparathyroidism. Those family members who had the mutation and were eligible
      for surgical treatment underwent total thyroidectomy and central compartment
      dissection. In those patients with high postoperative calcitonin levels, residual
      disease was sought with radiologic imaging, and follow-up was done with
      pentagastrin stimulation tests. RESULTS: Of the 21 family members screened, 10
      had the RET proto-oncogene mutation (codon 634, TGC->GGC) (5 females and 5 males;
      6 adults and 4 children). All the adults had bilateral medullary thyroid
      carcinoma (MTC); four of them had lymph node metastatic lesions, and one had
      metastatic involvement of the liver. Two adults had pheochromocytomas. Two family
      members were reported to have parathyroid hyperplasia, although both were
      normocalcemic. CONCLUSION: This family with MEN IIA showed classic mendelian
      autosomal dominant inheritance. All adult patients had MTC, two had
      pheochromocytomas, and two had parathyroid hyperplasia. Although one child had a
      high stimulated calcitonin level, the histopathologic findings were normal;
      another child with high stimulated calcitonin levels showed C-cell hyperplasia on
      histopathologic examination.

PMID- 11250765
TI  - Intractable diarrhea in hyperthyroidism: management with beta-adrenergic
      blockade.
AB  - OBJECTIVE: To describe a patient with intractable diarrhea and thyrotoxic Graves'
      disease, for whom b-adrenergic blockade ultimately proved to be effective therapy
      for the diarrhea, and to review the types of hyperthyroidism-associated diarrhea.
      METHODS: We present the clinical course of a young man with a prolonged siege of
      diarrhea that proved elusive to diagnostic inquiries and resistant to all means
      of management until its endocrine basis was discovered. Control of such cases
      with b-adrenergic blockade is discussed, as are the pathophysiologic bases of
      intestinal hypermotility in hyperthyroidism. RESULTS: A 26-year-old man with Down
      syndrome, and no prior gastrointestinal disorder, had insidious, chronic,
      constant diarrhea, which was associated with loss of 14 kg during a 5-month
      period. Numerous laboratory and imaging studies and endoscopic examinations
      failed to disclose the cause of the diarrhea. Furthermore, a broad range of
      antibiotics and other empiric remedies failed to control the problem. No other
      symptoms of hyperthyroidism were reported, but when the endocrinopathy was
      suspected and identified, the diarrhea was promptly controlled by treatment with
      propranolol. In patients with hyperthyroidism, two types of diarrheal disorders
      have been described-secretory diarrhea and steatorrhea; bile acid malabsorption
      may have a role in either of these settings. CONCLUSION: In addition to its
      capacity for blocking the peripheral effects of thyroid hormone on the heart and
      central nervous system, b-adrenergic blockade is effective in slowing intestinal
      transit time and ameliorating the uncommon diarrhea associated with
      hyperthyroidism. Thyroid hormone in excess, among its other possible effects on
      the gastrointestinal tract, may exert a stimulatory effect by means of
      intermediary sympathetic activation, as it does with the heart. Thus, sympathetic
      blockade can mimic the salutary effects on the gastrointestinal tract
      conventionally brought about by direct antithyroid therapy, and well before the
      hyperthyroid state per se is eliminated. The current patient illustrates the
      value of considering hyperthyroidism in the differential diagnosis of diarrhea of
      unknown cause.

PMID- 11250766
TI  - Acute extracapsular parathyroid hemorrhage: case report and review of the
      literature.
AB  - OBJECTIVE: To describe a patient with extracapsular parathyroid hemorrhage and
      review the signs and symptoms of this condition. METHODS: We report a case of
      extracapsular parathyroid hemorrhage in a patient with primary
      hyperparathyroidism and present an overview of previously reported cases.
      RESULTS: A 48-year-old woman with documented primary hyperparathyroidism, who was
      awaiting surgical intervention, had acute onset of a neck mass, neck pain, and
      dysphagia. She was found to have sustained a spontaneous extracapsular hemorrhage
      of a parathyroid adenoma. Hypercalcemia persisted, and she subsequently underwent
      curative parathyroidectomy for the primary hyperparathyroidism. We also
      identified 15 previously reported cases of extracapsular parathyroid hemorrhage
      and summarized the most common manifestations-most notably, a neck mass or
      swelling, ecchymoses of the neck and chest, dysphagia, neck pain, hoarseness, and
      dyspnea. CONCLUSION: Clinicians should be aware of the potential for occurrence
      of extracapsular parathyroid hemorrhage in patients with primary
      hyperparathyroidism. When this condition occurs, severe hypercalcemia or acute
      hypocalcemia may be present. Hypercalcemia is often persistent; however,
      autoinfarction of the parathyroid adenoma is possible.

PMID- 11250767
TI  - Propylthiouracil-induced perinuclear-staining antineutrophil cytoplasmic
      autoantibody-positive vasculitis in conjunction with pericarditis.
AB  - OBJECTIVE: To describe a case of propylthiouracil-induced vasculitis manifesting
      with pericarditis. METHODS: We present the first case report of a woman with
      hyperthyroidism treated with propylthiouracil in whom a syndrome of pericarditis,
      fever, and glomerulonephritis developed. Serologic testing and immunologic
      studies were done, and a pericardial biopsy was performed. RESULTS: A 25-year-old
      woman with Graves' disease had a febrile illness and evidence of pericarditis,
      which was confirmed by biopsy. Serologic evaluation revealed the presence of
      perinuclear-staining antineutrophil cytoplasmic autoantibodies (pANCA) against
      myeloperoxidase (MPO). Propylthiouracil therapy was withdrawn, and she was
      treated with a 1-month course of prednisone, which alleviated her symptoms. A
      literature review revealed no prior reports of pericarditis in anti-MPO pANCA
      positive vasculitis associated with propylthio- uracil therapy. CONCLUSION:
      Pericarditis may be the initial manifestation of drug-induced vasculitis
      attributable to propylthio- uracil therapy.

PMID- 11250768
TI  - Postmenopausal virilization, simple ovarian cyst, and hilus cell hyperplasia--is
      there an association?
AB  - OBJECTIVE: To report a case of virilizing ovarian hilus cell hyperplasia detected
      postmenopausally in association with a simple cyst and to review the related
      literature, including four similar cases. METHODS: Hormonal and pathologic
      studies were conducted, and ovarian venous catheterization was performed during
      total abdominal hysterectomy. RESULTS: In our 69-year-old female patient, serum
      testosterone levels were 508, >3,200, and 11 ng/dL, respectively, in peripheral
      blood preoperatively, in ovarian venous blood obtained intraoperatively, and in
      peripheral blood postoperatively. The wall of the cyst contained several clusters
      of hilus cells, which were also found asymmetrically lateralized to the affected
      ovary. CONCLUSION: Hilus cell hyperplasia should be suspected in any case of
      postmenopausal virilization in which ultrasonography or magnetic resonance
      imaging suggests the presence of a simple ovarian cyst.

PMID- 11250769
TI  - Free fatty acids-the link between obesity and insulin resistance.
AB  - OBJECTIVE: To present evidence that free fatty acids (FFA) are an important link
      between obesity and insulin resistance. METHODS: The role of FFA in peripheral
      insulin resistance, hepatic insulin resistance, insulin secretion, and type 2
      diabetes is discussed. RESULTS: Obesity is invariably associated with insulin
      resistance. In most obese subjects, plasma FFA levels are increased. Physiologic
      increases in plasma FFA levels cause insulin resistance in both diabetic and
      nondiabetic subjects by producing several metabolic defects: (1) FFA inhibit
      insulin-stimulated glucose uptake at the level of glucose transport or
      phosphorylation (or both); (2) FFA inhibit insulin-stimulated glycogen synthesis;
      and (3) FFA inhibit insulin-stimulated glucose oxidation. (This last-mentioned
      defect probably does not contribute to insulin resistance.) FFA probably also
      cause hepatic insulin resistance, which results in increased rates of endogenous
      glucose production in relationship to the prevailing degree of hyperinsulinemia.
      Lastly, FFA support between 30 and 50% of basal insulin secretion and potentiate
      glucose-stimulated insulin secretion in short-term and long-term settings. The
      stimulatory action of FFA on b-cells enables obese individuals who do not have a
      genetic predisposition to develop type 2 diabetes mellitus to compensate for
      their FFA-potentiated insulin resistance with an increase in FFA-mediated insulin
      secretion. In contrast, subjects who are genetically predisposed to develop type
      2 diabetes may be unable to secrete sufficient amounts of insulin to compensate
      for their FFA-induced insulin resistance. This situation will lead to an increase
      in blood glucose concentration and eventually to type 2 diabetes. CONCLUSION: FFA
      have been shown to have an important contributing role in the pathogenesis of
      insulin resistance in human obesity.

PMID- 11250770
TI  - Autoimmune thyroid dysfunction induced by interferon-alpha treatment for chronic
      hepatitis C: screening and monitoring recommendations.
AB  - OBJECTIVE: To analyze the proposed mechanisms of action of recombinant interferon
      alpha (IFN-a) in causing autoimmune thyroid dysfunction, to identify pretreatment
      risk factors, and to provide recommendations for screening and monitoring of
      thyroid dysfunction during IFN-a therapy for chronic hepatitis C. METHODS:
      Selected publications were reviewed to analyze the proposed mechanisms of
      autoimmune thyroid disorders. In addition, we examined the interrelationship of
      the thyroid and the liver, the occurrence of thyroid dysfunction in patients with
      chronic hepatitis C before and after IFN-a therapy, and the presence or absence
      of antithyroid antibodies in association with thyroid disease. Case reports were
      selected to demonstrate various IFN-a-induced thyroid dysfunction. RESULTS: IFN-a
      induces thyroid dysfunction in 3 to 14% of all treated patients with chronic
      hepatitis C, leading to hypothyroidism, hyperthyroidism, or thyroiditis. In a few
      patients, thyroid disease will develop in the absence of antithyroid antibodies,
      a scenario that suggests a nonimmune-mediated mechanism. More frequently,
      patients develop antithyroid antibodies, which may progress to overt thyroid
      dysfunction. Through its immunomodulatory properties, IFN-a seems to act through
      major histocompatibility complex class I antigens to produce antithyroid
      antibodies and thyroid disease. CONCLUSION: In patients receiving IFN-a therapy
      for chronic hepatitis C infection, identifiable risk factors for developing
      autoimmune thyroid dysfunction are preexisting overt thyroid or autoimmune
      disease, subclinical thyroid or autoimmune thyroid disease, and female gender.
      Pretreatment screening is recommended for all patients in whom IFN-a therapy is
      being considered, and periodic monitoring should be performed during such
      therapy. Thyroid disease need not be a contraindication to IFN-a therapy; early
      detection of subclinical or overt thyroid disease may allow uninterrupted
      continuation of IFN-a treatment.

PMID- 11250771
TI  - Should angiotensin-converting enzyme inhibitors be added to the water supply of
      patients with diabetes?

PMID- 11250772
TI  - Topical finasteride therapy in hirsutism.

PMID- 11250773
TI  - Androgens and prostate cancer: the plot thickens.

PMID- 11250774
TI  - Role of androgen receptor in prostate cancer.
AB  - The growth of prostate cancer is sensitive to androgen, and hormonal therapy has
      been used for treatment of advanced cancer. About 80% of prostate cancers
      initially respond to hormonal therapy, however, more than half of the responders
      gradually become resistant to this therapy. Changes in tumors from an androgen
      responsive to an androgen-unresponsive state have been widely discussed. Since
      androgen action is mediated by androgen receptor (AR), abnormalities of AR is
      believed to play an important role of the loss of androgen responsiveness in
      prostate cancer. This article focused on the role of AR in the progression of
      prostate cancer.

PMID- 11250775
TI  - Role of ions and ion channels in capacitation and acrosome reaction of
      spermatozoa.
AB  - Capacitation and acrosome reaction are important prerequisites of the
      fertilization process. Capacitation is a highly complex phenomenon occurring in
      the female genital tract, rendering the spermatozoa capable of binding and fusion
      with the oocyte. During capacitation various biochemical and biophysical changes
      occur in the spermatozoa and the spermatozoal membranes. Ions and ion channels
      also play important roles in governing the process of capacitation by changing
      the fluxes of different ions which in turn controls various characteristics of
      capacitated spermatozoa. Along with the mobilization of ions the generation of
      free radicals and efflux of cholesterol also plays an important role in the
      capacitation state of the spermatozoa. The generation of free radical and efflux
      of cholesterol change the mechanodynamic properties of the membrane by oxidation
      of the polyunsaturated lipids and by generating the cholesterol free patches. The
      process of capacitation renders the spermatozoa responsive to the inducers of the
      acrosome reaction. The glycoprotein zona pellucida 3 (ZP3) of the egg coat zona
      pellucida is the potent physiological stimulator of the acrosome reaction;
      progesterone, a major component of the follicular fluid, is also an inducer of
      the acrosome reaction. The inducers of the acrosome reaction cause the activation
      of the various ion-channels leading to high influxes of calcium, sodium and
      bicarbonate. The efflux of cholesterol during the process of capacitation alters
      the permeability of the membrane to the ions and generate areas which are prone
      to fusion and vesiculation process during the acrosome reaction. This review
      focuses mainly on effects of the ion and ion-channels, free radicals, and
      membrane fluidity changes during the process of capacitation and acrosome
      reaction.

PMID- 11250776
TI  - Resazurin reduction and other tests of semen quality and fertility of bulls.
AB  - AIM: This study was undertaken to compare the reduction in color of two dyes
      methylene blue (MBRT) and resazurin dye (RRT) with other tests of bull semen
      quality and to examine their relationship to fertility. METHODS: One hundred
      sixty-four ejaculates from 59 bulls were examined, processed, and used for 30,016
      inseminations. RESULTS: Bulls used in artificial insemination have been selected
      for high semen quality and fertility, and semen from these bulls averaged 80.6%
      unstained sperm, only 11% had abnormalities, and fertility ranged from 64% to
      76%. The MBRT and RRT were run with standardized sperm numbers to prevent sperm
      concentration from influencing the dye reduction time. A short RRT was correlated
      with higher fertility (r = -0.26) but MBRT was not correlated (r = -0.05, P >
      0.05). The correlations were low, but are typical and reflect the statistical
      effect of the large binomial variance associated with pregnancy or nonpregnancy
      being coded as 1 or 0. CONCLUSION: The fact that the RRT was significantly
      correlated with fertility when sperm numbers were standardized, and published
      reports that resazurin is useful for monitoring other semen characteristics,
      indicate that this dye may provide valuable information not given by other simple
      laboratory tests.

PMID- 11250777
TI  - Ethane dimethylsulphonate selectively destroys Leydig cells in the adult bonnet
      monkeys (Macaca radiata).
AB  - AIM: To study the effect of intratesticular administration of ethane-1,2
      dimethylsulphonate (EDS) which has been extensively used to selectively destroy
      Leydig cells in rats and study the role of gonadotropin in regulation of
      differentiation of Leydig cells (LC) in the adult male bonnet monkey. METHODS AND
      RESULTS: In vitro studies with cultured interstitial cells isolated from monkey
      testis revealed an inhibitory effect of EDS on LC as assessed by decrease in
      testosterone production. Intratesticular administration of EDS (5, 10, 20, 50
      mg/testis) resulted in a dose-dependent rapid decrease in serum testosterone
      levels, with a 65% decrease with 5 mg of EDS by the 3rd day, which returned to
      control levels by the 45th day. EDS treatment resulted in a significant decrease
      in testicular testosterone. In addition a significant decrease in [125I]hCG
      binding and phenylesterase activity in the interstitial cells was noticed.
      Histological analysis of the testes on the 5th day after administration of EDS
      revealed an interstitium devoid of LC indicating the destructive action of EDS.
      CONCLUSION: The monkey LC are sensitive to destructive action of EDS.

PMID- 11250778
TI  - Effects of tripchlorolide on the epididymides and testes of rats.
AB  - AIM: To further evaluate the antifertility effects of tripchlorolide, a
      derivative of triptolide produced at the extraction procedure of Tripterygium
      wilfordii Hook. f., in male rats and to investigate its sites and possible
      mechanisms of action. METHODS: In male rats, tripchlorolide was given by oral
      garage at a dose of 50 micrograms.kg-1.d-1 for 5 weeks, fertility was assessed by
      mating tests, and biochemical indices and light microscopic observation of the
      epididymides and testes were also performed. RESULTS: Administration of
      tripchlorolide at 50 micrograms.kg-1.d-1 for 3 weeks did not influence the
      fertility of male rats, but 5-week treatment rendered the rats infertile. The
      density and motility of spermatozoa collected from cauda epididymides were
      reduced significantly. The epididymal weights, as well as the L-carnitine
      concentration and alpha-glucosidase content in the epididymal fluid were
      decreased. There were no significant differences in alpha-glucosidase and acid
      phosphatase (ACP) in caput epididymal homogenates between the control and the
      experimental rats. Obvious morphological changes were observed in the epididymal
      spermatozoa, mainly including head and tail separation or acrosome curving.
      Sloughed spermatids were found in the seminifeous and epididymal tubules. In
      testicular homogenates, tripchlorolide had no influence on the lactate
      dehydrogenase-C4 (LDH-C4) and hyaluronidase activities. No apparent lesions were
      observed in the seminiferous and epididymal epithelium. CONCLUSION: At the dose
      level employed, tripchlorolide has a significant effect on the fertility in male
      rats and the primary sites of action may be spermatids and testicular and
      epididymal spermatozoa.

PMID- 11250779
TI  - Ureaplasma urealyticum infection and apoptosis of spermatogenic cells.
AB  - AIM: To study the relationship between Ureaplasma urealyticum (UU) infection and
      apoptosis of human spermatogenic cells. METHODS: Spermatogenic cells were
      observed under light microscope with Wright-Giemsa staining and by means of
      terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP)
      biotin nick-end labeling (TUNEL) technique. RESULTS: Apoptotic rate of UU
      infected males (15.5% +/- 6.8%) was significantly higher than that of controls
      (5.2% +/- 2.3%). CONCLUSION: Apoptosis of spermatogenic cells can be caused by UU
      infection, which provides further evidence for UU-induced male infertility.

PMID- 11250780
TI  - Non-invasive reversal of intraluminal vas deferens polymer injection-induced
      azoospermia--technology.
AB  - AIM: The rationale and technique underlying a novel concept of non-invasive
      removal of an intravasal vas deferens polymeric contraceptive drug to reverse
      drug injection-induced azoospermia are explained. Thus the conventional methods
      of surgical exploration to remove vas deferens plugs and intravasal injection of
      solvents to flush out contraceptive drugs are to be replaced by steps which will
      be readily accepted by subjects. METHODS: The approach is based upon the non
      invasive application of specific forces to various segments of the vas deferens
      so that non-sclerosing and non-tissue-adherent compounds, in particular styrene
      maleic anhydride (SMA) can be expelled. Forces are generated by palpation;
      percutaneous electrical stimulation; vibration application; and percussion. The
      forces help to propel the intravasal polymer towards the ejaculatory duct for
      expulsion during ejaculation. All aspects of the total technique are clinically
      acceptable, simple, atraumatic, unlikely to cause pain and discomfort even
      without tranquilizers, local or general anaesthetics. The procedure may be
      repeated several times in different sittings spaced apart by about one week to
      achieve adequate plug expulsion. RESULTS: Model experiments demonstrated the
      feasibility of the concept. The polymer was nonadherent and could be moved within
      the vas deferens by the application of specific forces. Sufficient removal was
      possible to enable spermatic fluid to be transported along a region previously
      occupied by the polymer. A corroborating subhuman primate study by an independent
      investigator has shown that the semen profile becomes normal following the
      reversal. CONCLUSION: Adoption of the new technique may provide a means of non
      surgical restoration of normal semen profile after a period of fertility control
      obtained by intravasal drug injection.

PMID- 11250781
TI  - Regeneration of neuronal nitric oxide synthase (nNOS)-containing nerve fibers in
      rat corpus cavernosum.
AB  - AIM: To investigate the effect of cavernous nerve injury on the nNOS-containing
      nerve fibers in rat corpus cavernosum. METHODS: Thirty-three male SD rats were
      randomized into 3 groups: 5 rats underwent pelvic exploration without transection
      of cavernous nerve as the sham-operated controls, the unilateral injury group (14
      rats) had the cavernous nerve cut on one side, and the bilateral injury group (14
      rats) had the nerves cut on both sides. Corpora cavernosa were harvested at the
      3rd week and 6th month after surgery. nNOS-positive nerve fibers were examined
      with strepavidin peroxidase immunohistochemistry techniques (SP method). RESULTS:
      After bilateral ablation, the nNOS-positive nerve fibers were significantly
      decreased at both the 3rd week (17 +/- 4) and the 6th month (16 +/- 4). For the
      unilateral injury group, the nNOS-positive nerve fibers were similarly decreased
      on the side of the neurotomy at the 3rd week (18 +/- 6), but by the 6th month,
      the number increased significantly (61 +/- 9) and approximated the level on the
      contralateral side (81 +/- 13). CONCLUSION: In rats after unilateral cavernous
      nerve ablation, nNOS-containing nerve fibers might regenerate 6 months after
      operation, but regeneration did not occur in animals with bilateral cavernous
      nerve injury. Results suggest that during pelvic radical surgery, the cavernous
      nerve should be preserved at least on one side in order to accomplish adequate
      regeneration.

PMID- 11250782
TI  - Reproductive characteristics of transgenic (TG) chickens carrying an exogenous
      gene.
AB  - An exogenous gene (lacZ/MiwZ) introduced into the germinal crescent region (GCR)
      of avian embryos was confirmed to be successfully transferred to the gonads via
      the primordial germ cells (PGCs). Following hatching, the chicks were raised
      until the stage of sexual maturation. The incorporation of MiwZ DNA was detected
      in male and female transgenic chickens, respectively. The normal male and female
      transgenic birds were subjected to artificial insemination according to routine
      methods. Fertilized eggs obtained from female transgenic chickens were incubated
      for 72 h and the embryos removed from the yolk were examined by X-gal staining to
      detect the introduction of MiwZ in the offspring. As a result, the expression of
      MiwZ was detected in the offspring. Furthermore, the presence of MiwZ in the
      extracts from embryos was also detected by polymerase chain reaction (PCR)
      analysis. In male transgenic chickens, the presence of injected MiwZ in the
      extracts from sperm was also confirmed. The exogenous gene introduced into the
      GCR migrated successfully to the gonad resulting in its incorporation into the
      offspring and spermatozoa of transgenic chickens.

PMID- 11250783
TI  - Application of pudendal evoked potentials in diagnosis of erectile dysfunction.
AB  - AIM: Extensive neurophysiological investigations were carried out in 100 healthy
      subjects and 84 patients with penile erectile dysfunction. METHODS: Following
      examinations were performed, spinal and scalp somatosensory evoked potentials
      (SEPs) to stimulation of the dorsal nerve of penis, motor evoked potentials
      (MEPs) from bulbocavernosus (BC) in response to scalp and spinal root
      stimulation, and measurement of sacral reflex latency (SRL) from anal sphincter
      (AS). RESULTS: In the healthy subjects, the mean sensory total conduction time
      (sensory TCT), as measured at the peak of the scalp P1 (P40) wave was 39.73 ms.
      The mean sensory central conduction time (sensory CCT = spinal-to-scalp
      conduction time) was 28.98 ms. The mean peripheral conduction time (PCP) was 9.40
      ms. Transcranial brain stimulation was performed by using a magnetic stimulator
      during voluntary contraction of the examined muscle. Spinal root stimulation was
      performed at rest. Motor total conduction time (motor TCT) to BC muscles was
      20.48 ms. Motor central conduction time (motor CCT) to sacral cord segments
      controlling BC muscles was 14.42 ms at rest. The mean SRL was 35.13 ms.
      CONCLUSION: Combined or isolated abnormalities of SEPs, MEPs, and SRL were found
      in patients with erectile dysfunction.

PMID- 11250784
TI  - Effect of vitamin E on human sperm motility and lipid peroxidation in vitro.
AB  - AIM: To assess the protective efficacy of vitamin E to counteract the reactive
      oxygen species (ROS) mediated damage on sperm motility, viability and lipid
      peroxidation. METHODS: Human semen samples were obtained from the local hospital.
      The split seminal fractions freed of seminal plasma were reconstituted in Ringer
      Tyrode and subjected to varied vitamin E concentrations (0.1-2 mmol/L). RESULTS:
      Dose-dependent improvement in both motility and viability accompanied by
      concomitant decrease in malondialdehyde (MDA--an end product of lipid
      peroxidation) following vitamin E supplementation was noticed. CONCLUSION:
      Vitamin E protects against the ROS mediated damage on spermatozoa. Vitamin E
      supplementation could be of clinical importance for prolonged spermatozoal
      storage whenever needed.

PMID- 11250785
TI  - Studies on apoptosis of spermatogenic cells in normal fertile men treated with
      supraphysiological doses of testosterone undecanoate.
AB  - AIM: To study the anti-spermatogenic mechanism of supra-physiological doses of
      testosterone undecanoate (TU). METHODS: Twenty fertile adult men received four
      intramuscular injections of TU at monthly intervals, 1000 mg upon admission and
      500 mg for the subsequent injections. The apoptotic germ cells in the semen were
      studied under light microscope with terminal deoxynucleotidyl transferase
      mediated dUTP-biotin nick end labeling (TUNEL) and Wright-Giemsa staining
      methods. RESULTS: After treatment, the sperm density and the number of
      spermatogenic cells in the semen were significantly decreased (P < 0.01), while
      the apoptotic ratios of spermatocytes and spermatids increased significantly (P <
      0.01) as compared with the pretreatment levels. Apoptosis was found to be
      augmented in the whole series of castoff spermatogenic cells. CONCLUSION: Besides
      its suppressive effect on spermatogenesis through a negative feed-back mechanism,
      TU enhances apoptosis of spermatogenic cells, which may be an additional
      mechanism of its anti-spermatogenic activity.

PMID- 11250786
TI  - Studies on plasma endothelin changes in varicocele patients.
AB  - AIM: To investigate the possible role endothelin may play in the pathogenesis of
      varicocele and varicocele-induced infertility. METHODS: In varicocele patients,
      radioimmunoassay is used to determine the blood endothelin concentration in the
      spermatic vein and the antecubital vein separately. RESULTS: The blood endothelin
      concentration of the spermatic vein (66.8 +/- 23.5 pg/mL) was significantly
      higher (P < 0.05) than that of the antecubital vein (55.3 +/- 25.3 pg/mL). The
      endothelin concentration in the spermatic vein in Grade II varicocele patients
      was not significantly different from that in Grade III patients (P = 0.87).
      CONCLUSION: The higher blood endothelin level in the spermatic vein may indicate
      the involvement of endothelin in the pathophysiology of varicocele and varicocele
      induced infertility.

PMID- 11250787
TI  - Fertility and sexual life of men after their forties and in older age.
AB  - Owing to the demographic development, the aging male will require more
      consideration in future. In contrast to a rapid decline of estradiol during
      menopause in women, the process of aging in the male is retarded and subject to
      high individual variations. Impairment of spermatogenesis is observed as a
      continuous process occurring over decades. However, only about 50 % of men in
      their eighties show complete loss of fertility. In principle, spermatogenesis may
      be retained well into senescence. Of importance for the individual health
      condition is the fact that the number of Leydig cells declines with advancing
      age. Thus, altered sex hormone concentrations in aging men result from both
      functional disturbances and a gradual reduction in Leydig cells. Furthermore, an
      impaired feed-back mechanism of the pituitary-gonadal axis occurs, with
      disappearance of the circadian testosterone (T) rhythm. LH and FSH levels are
      increased, and a reduced bioavailability of sex hormones is observed. Lower total
      testosterone concentrations in men over 60 years are accompanied by clinical
      signs of reduced virility, such as decreased muscle mass and strength as well as
      reduced sexual hair growth and libido. An age-related decline in androgen
      secretion and plasma testosterone levels therefore suggests the use of androgen
      supplementation. However, there is a lack of risk-benefit long-term studies.
      Increased research in the male is mandatory to meet the requirements of the aging
      population. This should include the availability of precise epidemiological data
      about the frequency of partial androgen deficiency in aging males (PADAM).

PMID- 11250789
TI  - Effect of testicular capsulotomy on fertility of rats.
AB  - AIM: To demonstrate the effect of capsulotomy on the fertility of male rats.
      METHODS: Testicular capsulotomy was carried out in immature (21 days) and adult
      (60 days) male rats. The fertility of them was assessed by cohabitation with
      proestrus females overnight and 20 days later, the females were examined for
      impregnation. Morphological changes at the site of the capsulotomy were observed
      under light microscope. RESULTS: In rats capsulotomized at Day 60, the fertility
      was gradually depressed and all the rats completely lost their fertility 2 months
      post-operation. At that time, a partial regeneration of the capsule at the site
      of capsulotomy was observed. Immature rats capsulotomized at Day 21 were found to
      possess normal fertility at maturity. The capsulotomy site was almost completely
      recovered 60 days post-operation. CONCLUSION: In male rats, testicular
      capsulotomy at the age of Day 60 will damage fertility. However, when capsulotomy
      is performed at Day 21, fertility is preserve.

PMID- 11250788
TI  - Cytokines in the BALB/c mouse testis in various conditions.
AB  - AIM: To investigate whether testosterone, estrogens, vasectomy, experimental
      cryptorchidism, varicocele or aging would induce changes in the cytokine
      environment of the mouse testis. METHODS: In adult male BALB/c mice, testosterone
      implants, estradiol benzoate, vasectomy, unilateral cryptorchidism, unilateral
      varicocele were administered/performed. The mice were followed up for different
      periods of time and were then sacrificed with testes incised for examination. The
      control mice received the vehicle or sham-operation. RESULTS: IL-10 was present
      in Leydig cells of nearly every testis and IL-10 + macrophages in 39% of testes.
      IL-6 was found in the testes of intact adult mice, mice treated with testosterone
      for 70 days, cryptorchid testes and sham-operated testes. CONCLUSION: Results
      suggest that IL-10 might be involved in the generation of the immunologically
      privileged microenvironment in the testis.

PMID- 11250790
TI  - Human sperm motility stimulating activity of a sulfono glycolipid isolated from
      Sri Lankan marine red alga Gelidiella acerosa.
AB  - AIM: To evaluate the sperm motility stimulating activity of a sulfono glycolipid
      (S-ACT-1) isolated from Gelidiella acerosa, a Sri Lankan marine red algae.
      METHODS: S-ACT-1, a white amorphous powder was separated from more polar
      fractions of the hexane soluble of 1:1 CH2Cl2/MeOH extract and subjected to 1H,
      13C NMR and IR Spectroscopy after reverse phase HPLC for identification. Effects
      of S-ACT-1 on human sperm motility was assessed in vitro at 10, 100 and 1,000
      microg/mL concentrations at 37 degrees C for 0, 5, 15, 30 and 60 min. RESULTS: S
      ACT-1 was identified as a glycolipid sulfate. The lower dose increased the sperm
      motility slightly, whilst the medium dose significantly increased the motility (P
      < 0.05) from 5 min of incubation reaching a peak at 15 min and the stimulant
      effect was sustained throughout the experimental period. Furthermore, the medium
      dose rendered 80% of the immotile viable sperm motile. In contrast, the highest
      dose impaired the sperm motility. The sperm stimulating activity of S-ACT-1 was
      dose-dependent and had a bell-shaped dose response curve for all the 5 incubation
      periods. CONCLUSION: S-ACT-1 of Gelidiella acerosa is a Sulfono glycolipid. S-ACT
      1 has a potent sperm motility stimulating activity in vitro and has the potential
      to be developed into a sperm stimulant.

PMID- 11250791
TI  - Evaluation for Madigan's prostatectomy in patients with benign prostatic
      hyperplasia.
AB  - AIM: To comparatively evaluate the efficacy and post-operative complications of
      the Madigan's prostatectomy (MPC) and suprapubic prostatectomy (SPPC). METHODS: A
      total of 43 patients with benign prostatic hyperplasia were divided into two
      groups: 21 underwent MPC and 22, SPPC. In all the patients, the international
      prostate symptom score (IPSS) and urinary pressure-flow studies were assessed
      before and 6 months after operation. The International Continence Society (ICS)
      nomogram, Abrams-Griffiths (AG) number and linear passive urethral resistance
      relation analysis (L-PURR) were used to diagnose and grade bladder outlet
      obstruction (BOO). The IPSS and the urodynamic parameters before and after
      operation, as well as the advantages and post-operative complications were
      recorded and compared. RESULTS: Patients of both the MPC and SPPC groups had a
      significant improvement in IPSS and urodynamic parameters. Obstruction was
      relieved in 81.0% of MPC and 86.4% of SPPC patients. MPC has the advantages of
      the absence of postoperative hematuria and post-catheter stricture, a shorter
      period of hospitalization, and lower incidence of retrograde ejaculation and
      erectile dysfunction. CONCLUSION: Both MPC and SPPC can effectively relieve BOO.
      MPC has certain advantages and a lower incidence of complications as compared
      with SPPC.

PMID- 11250792
TI  - Effect of nitrofurazone on the reproductive organs in adult male mice.
AB  - AIM: To study the effect of 5-nitro-2-furaldehyde semicarbazone (nitrofurazone),
      a derivative of nitrofuran, on male reproductive organs of Parkes (P) strain
      mice. METHODS: Mice were given nitrofurazone orally at a dose of 64 mg/kg body
      weight per day, for 10 and 20 days, and were killed 24 h and/or 56 days after the
      last treatment. Histological appearance of testis, motility and number of
      spermatozoa in cauda epididymidis, and biochemical indices in epididymis and
      seminal vesicle were evaluated. RESULTS: Histologically, testis showed marked
      regressive changes in the seminiferous tubules in mice treated with
      nitrofurazone. Ten days after treatment, there was much depletion of germ cells
      in the seminiferous tubules, and the germinal epithelium was lined mainly with
      Sertoli cells, spermatogonia, spermatocytes, and a few round spermatids;
      intraepithelial vacuoles and multinucleated giant cells were also observed in
      tubules. By 20 days, regressive changes in the seminiferous tubules were further
      pronounced, and pachytene spermatocytes were the most advanced germ cells noticed
      in the tubules. In severe cases, the tubules were lined with a thin layer of
      Sertoli cells and spermatogonia. The treatment also caused marked reductions in
      the motility and number of spermatozoa in the cauda epididymidis, in weight and
      the level of fructose in the seminal vesicle, and in sialic acid level in the
      epididymis. Fifty six days after drug withdrawal, the alterations induced in the
      reproductive organs returned to control levels. CONCLUSION: Our results suggest
      that nitrofurazone treatment in P mice induces marked alterations in the male
      reproductive organs, and that the alterations are reversible following cessation
      of treatment.

PMID- 11250793
TI  - Sympathetic skin response: a new test to diagnose erectile dysfunction.
AB  - AIM: Electrophysiological monitoring of the activity of the penile sympathetic
      skin responses (PSSR) in healthy men and patients with erectile dysfunction (ED).
      METHODS: PSSR were recorded from the skin of penis with disk electrodes at the
      time of electric stimulation of left median nerves. RESULTS: PSSR were recorded
      from all the healthy men and almost all the patients. In healthy men the latency
      of P0, the latency of N1, the duration of N1 and the amplitude of N1 were 1,249
      +/- 111 ms, 2,239 +/- 286 ms, 1,832 +/- 505 ms and 470 microV (median),
      respectively. In ED patients the latency of P0, the latency of N1, the duration
      of N1 and the amplitude of N1 were 1,467 +/- 183 ms (P < 0.01), 2,561 +/- 453 ms
      (P < 0.05), 2,560 +/- 861 ms ( P < 0. 01) and 91 microV ( P < 0.01),
      respectively. The normal latency of P0 was less than 1,471 ms. The normal
      amplitude of N1 was more than 235 microV. According to this normal value, of 20
      patients 11 showed longer latency of P0, and 14 showed lower amplitude of N1 as
      compared with those of normal subjects. CONCLUSION: PSSR can be used as an
      electrophysiological method in assisting the diagnosis of ED.

PMID- 11250794
TI  - Introduction of DT40 cells into chick embryos.
AB  - AIM: To examine the transfection of exogenous genes into chick embryos, applying
      the characteristics of avian leukosis virus (ALV)-induced chicken B cell line
      DT40 to the production of chimeric birds. METHODS: The DT40 cells incorporated
      with exogenous gene ( lacZ constructs encoding Escherichia coli beta
      galactosidase: beta-gal) were introduced into chick embryos by the injection of
      cells into stage X blastoderm. Manipulated eggs were incubated for 3 (trial 1) or
      6 (trial 2) days, and the expression of lacZ DNA was detected by a histochemical
      staining method of beta-galactosidase and polymerase chain reaction (PCR)
      analysis. RESULTS: The survival rates of the manipulated embryos incubated for 3
      days (stage 18-20: trial 1) and 6 days (stage 28, 30: trial 2) were about 42% and
      38%, respectively. The expression rates of the lacZ gene in the embryos in the
      trials 1 and 2 were about 60% and 23%, respectively, for the survived embryos.
      CONCLUSION: The rate of embryonic viability and expression rate of introduced
      genes were not so high, but it suggested the possibility of utilizing the DT40
      cells as a vector for carrying exogenous genes into chick embryos.

PMID- 11250795
TI  - Application of seminal germ cell morphology and semen biochemistry in the
      diagnosis and management of azoospermic subjects.
AB  - AIM: To evaluate whether the study of seminal germ cell morphology (SGCM) and
      semen biochemistry could be fruitfully utilized for the diagnosis and management
      of azoospermic subjects. METHODS: In the semen, mature and immature germ cells
      are contributed by the testes, 70% of glycerylphosphoryl choline (GPC) by the
      epididymis, fructose mostly or solely by the seminal vesicles and acid
      phosphatase [corrected] (ACP) by the prostate. In 16 normal volunteers, 12
      vasectomized subjects and 186 azoospermic subjects, these parameters have been
      studied and the data have been analyzed. RESULTS: Both mature and immature germ
      cells are absent in the semen of vasectomized subjects as well as in obstructive
      azoospermia; GPC level is also significantly decreased in both these groups. In
      cases with non-obstructive azoospermia immature germ cells are present and
      seminal GPC, ACP and fructose levels are normal. The diagnosis of obstructive and
      non-obstructive azoospermia based on these parameters correlated well with
      "correct" testicular biopsy findings. In some cases of azoospermia due to
      hypospermatogenesis or spermatogenic developmental arrest, the SGCM studies were
      very helpful in objectively monitoring the response of the germinal tissue to
      specific treatments. CONCLUSION: SGCM and semen biochemical parameters are very
      valuable non-invasive markers for differentiating obstructive from non
      obstructive azoospermia. The SGCM findings serve as a dependable non-invasive
      testicular marker with high predictive value.

PMID- 11250796
TI  - Evaluation of germ-cell kinetics in infertile patients with proliferating cell
      nuclear antigen proliferating index.
AB  - AIM: To explore the usefulness of proliferating cell nuclear antigen
      proliferating index (PCNA PI) in the pathological diagnosis and treatment of male
      infertility. METHODS: Testicular biopsy specimen obtained from 48 cases of male
      infertility and 2 normal controls were fixed and embedded. The sections were
      stained with anti-PCNA monoclonal antibodies or haematoxylin/eosin. Proliferating
      index (PI), expressed as the percentage of germ-cell nuclei positively stained
      with PCNA antibody, was assessed from more than 20 seminiferous tubules or 600
      germ-cells. RESULTS: The infertile patients were divided into 4 groups: Group 1,
      normal spermatogenesis (14 cases); Group 2, hypospermatogenesis (16 cases); Group
      3, germinal arrest (10 cases); Group 4, Sertoli cell only syndrome (8 cases). The
      PCNA PI of normal control testis was 86.5% (mean value). Group 3 had a
      significantly lower PCNA PI (29.8%) than normal testis; Group 1 and 2 had similar
      PIs (82.3% and 82.3%, respectively) as the control testis. PI of the negative
      control (Group 4) was 0 as no germ-cells were found. CONCLUSION: PCNA PI is
      useful for assessing germ-cell kinetics, especially for pathological diagnosis of
      germinal arrest which is difficult to differentiate by routine HE staining
      technique. In germinal arrest, there is a significantly lowered PCNA PI, which is
      an indication of DNA synthesis deterioration, suggesting the use of therapies be
      different from those for hypospermatogenesis.

PMID- 11250797
TI  - Adenoma of the posterior urethra: 131 case report.
AB  - AIM: A case-report on adenoma of the posterior urethra. METHODS: In 131 cases of
      adenoma of the posterior urethra, aged 17-79 (mean: 36.4) years, a detailed
      medical history was taken and urinalysis, urethroscopy, and prostatic specific
      antigen (PSA) immunohistochemical staining were performed. They were then treated
      with transurethral resection (TUR) or transurethral electric coagulation (TUEC).
      RESULTS: Hemospermia occurred in 51% of the cases, hematuria in 38%, blood
      overflow from the urethral orifice in 6%, and dysuria in 5%. The position of the
      tumor was at or around the verumontanum. The appearance of the tumor was similar
      to those of a papilla, a villus, a dactyl or polyp, or simply an engorgement. The
      tumor contained glandular alveoli and adeno-epithelial cells. PSA
      immunohistochemistry was positive in the cytoplasm and nucleus of the adeno
      epithelial cell. One hundred and tweenty-nine cases were cured after TUR or TUEC,
      while 2 patients recurred and were operated again. CONCLUSION: Adenoma of the
      posterior urethra is a common cause of hemospermia and hematuria in young men.
      Urethroscopic examination and biopsy are the principal diagnostic measures. TUR
      or TUEC are believed to be the treatment of choice with a short-term recurrence
      rate of around 1. 5%.

PMID- 11250798
TI  - Effect of ligustrum fruit extract on reproduction in experimental diabetic rats.
AB  - AIM: To study the effect of ligustrum fruit on spermatogenesis and blood gonadal
      hormones in diabetic rats. METHODS: Experimental diabetes was induced in male
      Wistar rats with streptozotocin. Ligustrum fruit extract was given by gastric
      gavage at a dose of crude drug 30 g x kg(-1) x d(-1) for 110 days. The serum
      gonadadotropic hormones and testosterone were determined on d 60 and testicular
      histology examined on d 110. RESULTS: In the control diabetic rats, the
      seminiferous tubules were dilated and the spermatogenic cells irregularly
      arranged. Spermatogenesis was arrested with the number of spermatids highly
      reduced and spermatozoa not observed. In the treated rats, all types of
      spermatogenic cells were practically normal. The serum luteinizing hormone (LH),
      follicle-stimulating hormone (FSH) and testosterone levels were higher in the
      treated than in the control rats, but the difference was insignificant.
      CONCLUSION: In experimental diabetic rats, ligustrum fruit extract protects the
      damaging effect of experimental diabetes on spermatogenesis.

PMID- 11250799
TI  - Human papillomavirus and p53 protein immunoreactivity in condylomata acuminatum
      and squamous cell carcinoma of penis.
AB  - AIM: To determine the immunoreactive pattern of human papillomavirus (HPV)
      antigen and p53 protein in condylomata acuminatum (CA) and squamous cell
      carcinoma (SCC) of penis. METHODS: Immunohistochemistry for HPV and p53 were
      performed in 40 specimens of formalin fixed, paraffin embedded tissues using a
      polyclonal (rabbit) antibody against HPV and a monoclonal (mouse) antibody
      against human p53 protein. Twenty one cases of CA and nineteen cases of SCC were
      examined. RESULTS: HPV antigen was detected in all 21 CA and 2 penile SCC. p53
      protein overexpression was observed in 12 of 19 (63%) SCC in which 6 cases were
      strong positive. Five of 21 CA (24%) showed low-grade p53 protein overexpression.
      CONCLUSION: CA is related to HPV infection and some cases show p53 protein low
      grade overexpression. In contrast, p53 protein overexpression is common in penile
      SCC, which is seldom related to HPV infection.

PMID- 11250800
TI  - Introduction: reviews of environmental health, 2001.

PMID- 11250802
TI  - Significant effects of mild endogenous hormonal changes in humans: considerations
      for low-dose testing.
AB  - We review the significant and adverse health effects that can occur with
      relatively small endogenous hormonal changes in pubertal and adult humans. We
      discuss the effects of hormonal changes that occur within normal physiologic
      ranges--such as the rising levels of estrogen in peripuberty, which cause growth
      spurts at low levels and then the fusion of epiphyses at higher levels--and the
      hormonal variations during the menstrual cycle and their relation to genital
      phenotypic changes and intercurrent disease evolution. We turn next to adaptive
      changes in gonadal and other functions during aging, exercise, stress,
      starvation, and chronic diseases, which can serve as models for the effects of
      exogenous, hormonally active compounds. Then we review the states of borderline
      hormonal imbalances such as subclinical (having few or very mild symptoms, if
      any) hypothyroidism or hyperthyroidism, glucose intolerance, and other endocrine
      conditions. Finally, we review the deleterious systemic effects of gonadal
      imbalance. Information stemming from clinical observations leads to the concept
      of "no threshold" within the endocrine system and thus illustrates the importance
      of considering low-dose testing for chemicals that interfere with hormonal
      activity. We also urge attention to more sensitive, less visible end points such
      as osteoporosis, increased risk for cardiovascular disease, or cognitive changes.

PMID- 11250801
TI  - Cross-species and interassay comparisons of phytoestrogen action.
AB  - This paper compiles animal and human data on the biologic effects and exposure
      levels of phytoestrogens in order to identify areas of research in which direct
      species comparisons can be made. In vitro and in vivo assays of phytoestrogen
      action and potency are reviewed and compared to actions, dose-response
      relationships, and estimates of exposure in human subjects. Binding studies show
      that the isoflavonoid phytoestrogens are high-affinity ligands for estrogen
      receptors (ERs), especially ER beta, but have lower potency in whole-cell assays,
      perhaps because of interactions with binding proteins. Many other enzymatic
      actions require concentrations higher than those normally seen in plasma. In vivo
      data show that phytoestrogens have a wide range of biologic effects at doses and
      plasma concentrations seen with normal human diets. Significant in vivoresponses
      have been observed in animal and human tests for bone, breast, ovary, pituitary,
      vasculature, prostate, and serum lipids. The doses reported to be biologically
      active in humans (0.4--10 mg/kg body weight/day) are lower than the doses
      generally reported to be active in rodents (10--100 mg/kg body weight/day),
      although some studies have reported rodent responses at lower doses. However,
      available estimates of bioavailability and peak plasma levels in rodents and
      humans are more similar. Steroidogenesis and the hypothalamic-pituitary-gonadal
      axis appear to be important loci of phytoestrogen actions, but these inferences
      must be tentative because good dose-response data are not available for many end
      points. The similarity of reported proliferative and antiproliferative doses
      illustrates the need for fuller examination of dose-response relationships and
      multiple end points in assessing phytoestrogen actions.

PMID- 11250803
TI  - Molecular and cellular mechanisms of cardiotoxicity.
AB  - Cardiotoxicity resulting from detrimental environmental insults has been
      recognized for a long time. However, extensive studies of the mechanisms involved
      had not been undertaken until recent years. Advances in molecular biology provide
      powerful tools and make such studies possible. We are gathering information about
      cellular events, signaling pathways, and molecular mechanisms of myocardial
      toxicologic responses to environmental toxicants and pollutants. Severe acute
      toxic insults cause cardiac cell death instantly. In the early response to mild
      environmental stimuli, biochemical changes such as alterations in calcium
      homeostasis occur. These may lead to cardiac arrhythmia, which most often is
      reversible. Prolonged stimuli activate transcription factors such as activator
      protein-1 through elevation of intracellular calcium and the subsequent
      activation of calcineurin. Upregulation by activated transcription factors of
      hypertrophic genes results in heart hypertrophy, which is a short-term adaptive
      response to detrimental factors. However, further development of hypertrophy will
      lead to severe and irreversible cardiomyopathy, and eventually heart failure.
      From cardiac hypertrophy to heart failure, myocardial cells undergo extensive
      biochemical and molecular changes. Cardiac hypertrophy causes tissue
      hypoperfusion, which activates compensatory mechanisms such as production of
      angiotensin II and norepinephrine. Both further stimulate cardiac hypertrophy
      and, importantly, activate counterregulatory mechanisms including overexpression
      of atrial natriuretic peptide and b-type natriuretic peptide, and production of
      cytokines such as tumor necrosis factor-alpha. This counterregulation leads to
      myocardial remodeling as well as cell death through apoptosis and necrosis. Cell
      death through activation of mitochondrial factors and other pathways constitutes
      an important cellular mechanism of heart failure. Our current knowledge of
      cardiotoxicity is limited. Further extensive studies are warranted for a
      comprehensive understanding of this field.

PMID- 11250805
TI  - Polybrominated diphenyl ethers: occurrence, dietary exposure, and toxicology.
AB  - Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in plastics
      (concentration, 5--30%) and in textile coatings. Commercial products consist
      predominantly of penta-, octa-, and decabromodiphenyl ether mixtures, and global
      PBDE production is about 40,000 tons per year. PBDEs are bioaccumulated and
      biomagnified in the environment, and comparatively high levels are often found in
      aquatic biotopes from different parts of the world. During the mid-1970--1980s
      there was a substantial increase in the PBDE levels with time in both sediments
      and aquatic biota, whereas the latest Swedish data (pike and guillemot egg) may
      indicate that levels are at steady state or are decreasing. However,
      exponentially increasing PBDE levels have been observed in mother's milk during
      1972--1997. Based on levels in food from 1999, the dietary intake of PBDE in
      Sweden has been estimated to be 0.05 microg per day. Characteristic end points of
      animal toxicity are hepatotoxicity, embryotoxicity, and thyroid effects as well
      as maternal toxicity during gestation. Recently, behavioral effects have been
      observed in mice on administration of PBDEs during a critical period after birth.
      Based on the critical effects reported in available studies, we consider the
      lowest-observed-adverse-effect level (LOAEL) value of the PBDE group to be 1
      mg/kg/day (primarily based on effects of pentaBDEs). In conclusion, with the
      scientific knowledge of today and based on Nordic intake data, the possible
      consumer health risk from PBDEs appears limited, as a factor of over 10(6)
      separates the estimated present mean dietary intake from the suggested LOAEL
      value. However, the presence of many and important data gaps, including those in
      carcinogenicity, reproduction, and developmental toxicity, as well as additional
      routes of exposure, make this conclusion only preliminary. Moreover, the time
      trend of PBDEs in human breast milk is alarming for the future.

PMID- 11250804
TI  - Pesticides and breast cancer risk: a review of DDT, DDE, and dieldrin.
AB  - Established risk factors for breast cancer explain breast cancer risk only
      partially. Hence, there has been interest in evaluating what role environmental
      chemicals, especially those with evidence of being hormonally active agents, play
      in breast cancer risk. Organochlorine pesticides have received the most attention
      because of their persistence in the environment, ability to concentrate up the
      food chain, continued detection in the food supply and breast milk, and ability
      to be stored in the adipose tissue of animals and humans. Although several early
      descriptive studies and a cohort study identified a strong positive association
      with breast cancer risk and adipose or blood levels of the organochlorine
      pesticide dichlorodiphenyltrichloroethane (DDT) and/or its metabolite
      dichlorodiphenyldichloroethylene (DDE), most of the more recent case--control and
      nested case--control studies have not supported this association. In this review
      I discuss these findings and explore how exposure to different forms of DDT with
      varying estrogenicities may have affected the results of these studies. I also
      address how other factors influence the interpretation of the studies on DDT,
      DDE, and breast cancer risk. These include the effect of analytic methods,
      dietary factors, menopausal status, use of different types of control
      populations, lactation history, estrogen receptor status, ethnic/racial
      subgroups, breast tumor characteristics, and polymorphisms. I also discuss the
      emerging research on whether serum levels of the persistent organochlorine
      insecticide dieldrin are related to breast cancer risk in Danish and American
      women. Further research needs are also identified.

PMID- 11250806
TI  - The value of plants used in traditional medicine for drug discovery.
AB  - In this review we describe and discuss several approaches to selecting higher
      plants as candidates for drug development with the greatest possibility of
      success. We emphasize the role of information derived from various systems of
      traditional medicine (ethnomedicine) and its utility for drug discovery purposes.
      We have identified 122 compounds of defined structure, obtained from only 94
      species of plants, that are used globally as drugs and demonstrate that 80% of
      these have had an ethnomedical use identical or related to the current use of the
      active elements of the plant. We identify and discuss advantages and
      disadvantages of using plants as starting points for drug development,
      specifically those used in traditional medicine.

PMID- 11250807
TI  - Methods to identify and characterize developmental neurotoxicity for human health
      risk assessment: overview.

PMID- 11250808
TI  - Methods to identify and characterize developmental neurotoxicity for human health
      risk assessment. I: behavioral effects.
AB  - Alterations in nervous system function after exposure to a developmental
      neurotoxicant may be identified and characterized using neurobehavioral methods.
      A number of methods can evaluate alterations in sensory, motor, and cognitive
      functions in laboratory animals exposed to toxicants during nervous system
      development. Fundamental issues underlying proper use and interpretation of these
      methods include a) consideration of the scientific goal in experimental design,
      b) selection of an appropriate animal model, c) expertise of the investigator, d)
      adequate statistical analysis, and e) proper data interpretation. Strengths and
      weaknesses of the assessment methods include sensitivity, selectivity,
      practicality, and variability. Research could improve current behavioral methods
      by providing a better understanding of the relationship between alterations in
      motor function and changes in the underlying structure of these systems. Research
      is also needed to develop simple and sensitive assays for use in screening
      assessments of sensory and cognitive function. Assessment methods are being
      developed to examine other nervous system functions, including social behavior,
      autonomic processes, and biologic rhythms. Social behaviors are modified by many
      classes of developmental neurotoxicants and hormonally active compounds that may
      act either through neuroendocrine mechanisms or by directly influencing brain
      morphology or neurochemistry. Autonomic and thermoregulatory functions have been
      the province of physiologists and neurobiologists rather than toxicologists, but
      this may change as developmental neurotoxicology progresses and toxicologists
      apply techniques developed by other disciplines to examine changes in function
      after toxicant exposure.

PMID- 11250809
TI  - Methods to identify and characterize developmental neurotoxicity for human health
      risk assessment. II: neuropathology.
AB  - Neuropathologic assessment of chemically induced developmental alterations in the
      nervous system for regulatory purposes is a multifactorial, complex process. This
      calls for careful qualitative and quantitative morphologic study of numerous
      brains at several developmental stages in rats. Quantitative evaluation may
      include such basic methods as determination of brain weight and dimensions as
      well as the progressively more complex approaches of linear, areal, or
      stereologic measurement of brain sections. Histologic evaluation employs routine
      stains (such as hematoxylin and eosin), which can be complemented by a variety of
      special and immunohistochemical procedures. These brain studies are augmented by
      morphologic assessment of selected peripheral nervous system structures. Studies
      of this nature require a high level of technical skill as well as special
      training on the part of the pathologist. The pathologist should have knowledge of
      normal microscopic neuroanatomy/neuronal circuitry and an understanding of basic
      principles of developmental neurobiology, such as familiarity with the patterns
      of physiologic or programmed cell de

PMID- 11250813
TI  - Advances in phytoremediation.
AB  - Phytoremediation is the use of plants to remedy contaminated soils, sediments,
      and/or groundwater. Sorption and uptake are governed by physicochemical
      properties of the compounds, and moderately hydrophobic chemicals (logarithm
      octanol--water coefficients = 1.0--3.5) are most likely to be bioavailable to
      rooted, vascular plants. Some hydrophilic compounds, such as methyl-tert
      butylether and 1,4-dioxane, may also be taken up by plants via hydrogen bonding
      with transpiration water. Organic chemicals that pass through membranes and are
      translocated to stem and leaf tissues may be converted (e.g., oxidized by
      cytochrome P450s), conjugated by glutathione or amino acids, and
      compartmentalized in plant tissues as bound residue. The relationship between
      metabolism of organic xenobiotics and toxicity to plant tissues is not well
      understood. A series of chlorinated ethenes is more toxic to hybrid poplar trees
      (Populus deltoides x nigra, DN-34) than are the corresponding chlorinated
      ethanes. Toxicity correlates best with the number of chlorine atoms in each
      homologous series. Transgenic plants have been engineered to rapidly detoxify and
      transform such xenobiotic chemicals. These could be used in phytoremediation
      applications if issues of cost and public acceptability are overcome.

PMID- 11250812
TI  - Climate change and mosquito-borne disease.
AB  - Global atmospheric temperatures are presently in a warming phase that began 250-
      300 years ago. Speculations on the potential impact of continued warming on human
      health often focus on mosquito-borne diseases. Elementary models suggest that
      higher global temperatures will enhance their transmission rates and extend their
      geographic ranges. However, the histories of three such diseases--malaria, yellow
      fever, and dengue--reveal that climate has rarely been the principal determinant
      of their prevalence or range; human activities and their impact on local ecology
      have generally been much more significant. It is therefore inappropriate to use
      climate-based models to predict future prevalence.

PMID- 11250814
TI  - Analysis of inflorescence organogenesis in eastern gamagrass, Tripsacum
      dactyloides (Poaceae): the wild type and the gynomonoecious gsf1 mutant.
AB  - Inflorescence organogenesis of a wild-type and a gynomonoecious (pistillate)
      mutant in Tripsacum dactyloides was studied using scanning electron microscopy.
      SEM (scanning electron microscope) analysis indicated that wild-type T.
      dactyloides (Eastern gamagrass) expressed a pattern of inflorescence
      organogenesis that is observed in other members of the subtribe Tripsacinae (Zea:
      maize and teosinte), family Poaceae. Branch primordia are initiated acropetally
      along the rachis of wild-type inflorescences in a distichous arrangement. Branch
      primordia at the base of some inflorescences develop into long branches, which
      themselves produce an acropetal series of distichous spikelet pair primordia. All
      other branch primordia function as spikelet pair primordia and bifurcate into
      pedicellate and sessile spikelet primordia. In all wild-type inflorescences
      development of the pedicellate spikelets is arrested in the proximal portion of
      the rachis, and these spikelets abort, leaving two rows of solitary sessile
      spikelets. Organogenesis of spikelets and florets in wild-type inflorescences is
      similar to that previously described in maize and the teosintes. Our analysis of
      gsf1 mutant inflorescences reveals a pattern of development similar to that of
      the wild type, but differs from the wild type in retaining (1) the pistillate
      condition in paired spikelets along the distal portion of the rachis and (2) the
      lower floret in sessile spikelets in the proximal region of the rachis. The gsf1
      mutation blocks gynoecial tissue abortion in both the paired-spikelet and the
      unpaired-spikelet zone. This study supports the hypothesis that both femaleness
      and maleness in Zea and Tripsacum inflorescences are derived from a common
      developmental pathway. The pattern of inflorescence development is not
      inconsistent with the view that the maize ear was derived from a Tripsacum
      genomic background.

PMID- 11250815
TI  - Developmental morphology of the thalloid Hydrobryum japonicum (Podostemaceae).
AB  - We describe the unique development and branching of lobed thalli in Hydrobryum
      japonicum. Lobe formation begins with meristem initiation at random sites near
      the thallus margin fringed by protective tissues. As the protective tissues are
      successively peeled off particularly in the growing new lobes, the lobes become
      naked and then become fringed again by new protective tissues that develop from
      the marginal part of the new meristems. Subsequently the meristems become less
      active and are differentiated into parenchymatous ground tissue at maturity. The
      random pattern of meristem formation during the sporadic development gives rise
      to a nonorderly branching pattern of the thalli. Some other lobes (~10%) are
      regenerated from injured parts of the thalli. The vegetative shoots arise
      endogenously near the thallus margin and are enclosed by the nonvascular strand
      nets. The rudimentary shoot apices remain embedded in the thalli. The thalli,
      though remarkably different from typical roots of other angiosperms, might be
      extremely transformed roots.

PMID- 11250811
TI  - Aldrin and dieldrin: a review of research on their production, environmental
      deposition and fate, bioaccumulation, toxicology, and epidemiology in the United
      States.
AB  - In the last decade four international agreements have focused on a group of
      chemical substances known as persistent organic pollutants (POPs). Global
      agreement on the reduction and eventual elimination of these substances by
      banning their production and trade is a long-term goal. Negotiations for these
      agreements have focused on the need to correlate data from scientists working on
      soil and water sampling and air pollution monitoring. Toxicologists and
      epidemiologists have focused on wildlife and human health effects and
      understanding patterns of disease requires better access to these data. In the
      last 20 years, substantial databases have been created and now are becoming
      available on the Internet. This review is a detailed examination of 2 of the 12
      POPs, aldrin and dieldrin, and how scientific groups identify and measure their
      effects. It draws on research findings from a variety of environmental monitoring
      networks in the United States. An overview of the ecologic and health effects of
      aldrin and dieldrin provides examples of how to streamline some of the programs
      and improve access to mutually useful scientific data. The research groups are
      located in many government departments, universities, and private organizations.
      Identifying databases can provide an "information accelerator" useful to a larger
      audience and can help build better plant and animal research models across
      scientific fields.

PMID- 11250816
TI  - Biomechanics and anatomy of cladode junctions for two Opuntia (Cactaceae) species
      and their hybrid.
AB  - Hybridization between the introduced arborescent Opuntia ficus-indica and the
      native shrubby O. littoralis has led to populations, referred to as O.
      "occidentalis," which form thickets that can dominate hillsides of chaparral and
      that can survive fires. Because the thickets apparently develop via vegetative
      reproduction, O. "occidentalis" was hypothesized to have a greater ability than
      its parent species to reproduce vegetatively due to weaker cladode junctions. Of
      the three taxa, the junctions for O. "occidentalis" had the least amount of wood,
      despite having cladode masses and junction cross-sectional areas similar to those
      of O. littoralis. The cladodes of O. "occidentalis" resisted deflection about
      their junctions the least and their junctions required the least amount of
      applied mass and the smallest bending moment to fail mechanically. The junction
      wood for all three taxa consisted mostly of parenchyma, with lesser amounts of
      cells with thickened secondary cell walls, indicating that some junction strength
      depended on hydrostatic pressure, especially for terminal junctions. Libriform
      fibers, which contribute to support and resist bending moments, were about 80%
      less frequent in the sub-subterminal junctions of O. "occidentalis" than in O.
      ficus-indica and O. littoralis. Vascular tracheids, which probably reduced shear
      among cells in the wood, were 90% less frequent in the terminal and sub
      subterminal junction wood of O. "occidentalis" compared to O. littoralis. Thus
      wood characteristics can account for the weaker junctions of O. "occidentalis"
      compared to those of O. ficus-indica and O. littoralis, which apparently
      increases the ability of the hybrid to reproduce vegetatively.

PMID- 11250817
TI  - What data determine whether a plant taxon is distinct enough to merit legal
      protection? A case study of Sedum integrifolium (Crassulaceae).
AB  - Measures of molecular and morphological genetic variation are often used to set
      conservation priorities and design management strategies for plant taxa.
      Evaluated together they can give insights into a taxon's evolutionary status that
      neither data type alone can achieve. We investigated the distinctness and
      variability of Sedum integrifolium ssp. leedyi, a federally and state-listed
      taxon, from its conspecific relatives using 33 random amplified polymorphic DNA
      (RAPD) markers (253 plants) and 37 morphological characters from 1308 common
      garden-grown plants. We included S. integrifolium ssp. leedyi (four populations),
      its conspecific relatives (11 populations), and S. rosea and S. rhodanthum
      populations in our study. The morphological and molecular data correspond in
      showing that S. integrifolium ssp. leedyi populations are highly distinct.
      However, the data sets differ in their estimates of the relatedness of some S.
      integrifolium ssp. leedyi populations and in the percentage variation detected
      due to differences among them (25 and 9-13% for the molecular and morphological
      data, respectively) suggesting little gene flow among populations and some
      differentiation, possibly from selective pressures. Given our data, we recommend
      that S. integrifolium ssp. leedyi merits protection under the U.S. Endangered
      Species Act and that its populations be managed as distinct units.

PMID- 11250818
TI  - Correlated evolution of chloroplast heat shock protein expression in closely
      related plant species.
AB  - Interspecific variation in chloroplast low molecular weight (cLMW) HSP (heat
      shock protein) expression was examined with respect to phylogeny, species
      specific leaf area, chlorophyll fluorescence, and mean environmental conditions
      within species ranges. Eight species of Ceanothus (Rhamnaceae) were heat shocked
      for 4 h at several different temperatures. Leaf samples were collected
      immediately after the heat shock, and cLMW HSP expression was quantified using
      Western blots. At 45 degrees C species from the subgenus Cerastes had
      significantly greater cLMW HSP expression than species from the subgenus
      Ceanothus. Specific leaf area was negatively correlated with cLMW HSP expression
      after the 45 degrees C heat treatment. In addition, chlorophyll fluorescence
      (F(v)/F(m)) 1 h after the heat shocks was positively correlated with cLMW HSP
      expression. Contrary to our prediction, there was no correlation between July
      maximum temperature within species ranges and cLMW HSP expression. These results
      suggest that evolutionary differentiation in cLMW HSP expression is associated
      with leaf physiological parameters and related aspects of life history, yet
      associations between climatic conditions within species ranges and cLMW HSP
      expression require further study.

PMID- 11250810
TI  - Methods to identify and characterize developmental neurotoxicity for human health
      risk assessment. III: pharmacokinetic and pharmacodynamic considerations.
AB  - We review pharmacokinetic and pharmacodynamic factors that should be considered
      in the design and interpretation of developmental neurotoxicity studies.
      Toxicologic effects on the developing nervous system depend on the delivered
      dose, exposure duration, and developmental stage at which exposure occurred.
      Several pharmacokinetic processes (absorption, distribution, metabolism, and
      excretion) govern chemical disposition within the dam and the nervous system of
      the offspring. In addition, unique physical features such as the presence or
      absence of a placental barrier and the gradual development of the blood--brain
      barrier influence chemical disposition and thus modulate developmental
      neurotoxicity. Neonatal exposure may depend on maternal pharmacokinetic processes
      and transfer of the xenobiotic through the milk, although direct exposure may
      occur through other routes (e.g., inhalation). Measurement of the xenobiotic in
      milk and evaluation of biomarkers of exposure or effect following exposure can
      confirm or characterize neonatal exposure. Physiologically based pharmacokinetic
      and pharmacodynamic models that incorporate these and other determinants can
      estimate tissue dose and biologic response following in utero or neonatal
      exposure. These models can characterize dose--response relationships and improve
      extrapolation of results from animal studies to humans. In addition,
      pharmacologic data allow an experimenter to determine whether exposure to the
      test chemical is adequate, whether exposure occurs during critical periods of
      nervous system development, whether route and duration of exposure are
      appropriate, and whether developmental neurotoxicity can be differentiated from
      direct actions of the xenobiotic.

PMID- 11250819
TI  - Fly-pollinated Pleurothallis (Orchidaceae) species have high genetic variability:
      evidence from isozyme markers.
AB  - We conducted an isozyme study in 22 populations of five Pleurothallis
      (Orchidaceae) species (12 loci in nine enzymatic systems). The genetic
      variability in all populations is surprisingly high (P = 58-83%, A = 2.1-3.8,
      H(e) = 0.25-0.43) in spite of the fact that the five species are pollinated by
      small flies whose behavior enables self-pollination. We suggest that self
      incompatibility, inbreeding depression, and mechanical barriers that prevent self
      pollination in these species are responsible for the maintainance of the high
      genetic variability. These traits are uncommon in Orchidaceae, but have been
      observed in these and some other species pollinated by flies or other pollinators
      with behavior that facilitates self-pollination. The genetic similarity among
      conspecific populations is also high for species with very short-range flying
      pollinators. Only one population of P. teres presented values of genetic
      similarity lower than usually observed in allopatric conspecific populations.
      Morphology, however, does not support its segregation as a new taxon. All species
      can be recognized by their enzymatic patterns, and the results agree with
      recently proposed taxonomic realignments. Conversely, the supposed affinities
      among these species based on floral morphology are not supported, and we
      hypothesize that it may be due to convergence in species with similar
      pollinators.

PMID- 11250820
TI  - Interspecific and intraspecific variation in seed size and germination
      requirements of Sarracenia (Sarraceniaceae).
AB  - Seed size and germination requirements of eight (of nine) Sarracenia species, and
      13 populations of S. purpurea were studied. All species except for S. purpurea
      are restricted to the southeastern United States, whereas S. purpurea ranges
      across Canada, southward along the eastern United States into Maryland and
      Virginia (S. purpurea ssp. purpurea), and from New Jersey southward into northern
      Florida and the coast of the Gulf of Mexico (S. purpurea ssp. venosa). I tested
      the hypotheses that dormancy-breaking requirements vary predictably among species
      across a latitudinal gradient. I also sought to determine whether seed size and
      germination requirements were useful characters for resolving systematic and
      phylogenetic questions within this genus. Seed size varied significantly among
      species, but variability in seed size within S. purpurea exceeded the variability
      in seed size observed across all eight species studied. Seeds of all species are
      morphophysiologically dormant upon dispersal. Length of required cool, moist
      pretreatment varied among species, and germination in higher latitude populations
      is enhanced with longer pretreatment. In contrast, variability in germination
      requirements of subspecies, varieties, and populations of the geographically wide
      ranging S. purpurea was not related clearly to geographic location (latitude or
      elevation). Germination requirements do not map onto a proposed phylogeny of
      Sarracenia, but observed differences in germination requirements of S. purpurea
      ssp. venosa var. burkii relative to other populations of S. purpurea support the
      recent proposal to elevate this variety to species status.

PMID- 11250821
TI  - Drought stress, plant water status, and floral trait expression in fireweed,
      Epilobium angustifolium (Onagraceae).
AB  - In a controlled environment, we artificially induced drought during flowering of
      Epilobium angustifolium, an animal-pollinated plant. Leaf water potential
      (psi(l)) and floral traits were monitored over a 12-d period of soil moisture
      depletion. Soil moisture depletion induced drought stress over time, as revealed
      by significant treatment * day interactions for predawn and midday psi(l). Nectar
      volume and flower size showed significant negative responses to drought stress,
      but nectar sugar concentration did not vary between treatments. Floral traits
      were more buffered from drought than leaf water potentials. We used path analysis
      to examine direct and indirect effects of psi(l) on floral traits for plants in
      well-watered (control) vs. drought treatments. According to the best-fit path
      models, midday psi(l) has significant positive effects on flower size and nectar
      volume in both environments. However, for controls midday psi(l) also had a
      significant negative effect on nectar sugar concentration. Results indicate that
      traits influencing floral attractiveness to pollinators in E. angustifolium vary
      with plant water status, such that pollinator-mediated selection could indirectly
      target physiological or biochemical controls on psi(l). Moreover, under mesic
      conditions selection for greater nectar sugar reward may be constrained by the
      antagonistic effects of plant water status on nectar volume and sugar
      concentration.

PMID- 11250822
TI  - Pollinator-mediated selection on a flower color polymorphism in experimental
      populations of Antirrhinum (Scrophulariaceae).
AB  - We quantified pollinator visit behavior, pollen receipt and export, and changes
      in allele and genotype frequencies from initial Hardy- Weinberg conditions in
      experimental arrays of two color morphs of snapdragons (Antirrhinum majus)
      visited by freely foraging bumble bees (Bombus appositus and B. flavifrons). The
      number of pollen grains received by a flower depended most on the number of
      pollinator visits to the flower, whereas the number of grains exported was best
      predicted by the total time pollinators spent inside the flower. The pattern of
      mating generally was assortative with respect to color, as bees tended to
      overvisit one color or the other within a foraging bout. In arrays where nectar
      was augmented in one color, the augmented color received both more visits and
      longer visits. Allele and genotype frequencies in offspring samples were in
      accord with qualitative expectations based on the pollinator observations,
      demonstrating that pollinators can directly influence the evolution of single
      locus floral traits, at least under simplified experimental conditions.

PMID- 11250823
TI  - Flowering phenology, display size, and fruit set in an understory dioecious
      shrub, Aucuba japonica (Cornaceae).
AB  - I investigated the effects of display size and flowering phenology on fruit set
      in Aucuba japonica, an understory dioecious shrub pollinated by opportunistic
      insects. Natural variations in display size, flowering phenology, and fruit set
      were monitored in 1997. A hand-pollination experiment was also conducted to check
      whether pollen limitation was a factor in fruit set in the field. Increases in
      floral display size did not affect fruit set; the proportion of flowers that set
      fruit was almost constant irrespective of the total number of flowers per
      inflorescence, the total number of inflorescences per plant, and the total number
      of flowers per plant. The hand-pollination experiment showed that fruit set was
      not pollen limited despite the low mating probability that resulted from the
      combination of dioecism and the species' dependence on opportunistic pollinators.
      This was due, in part, to the fact that female flowers did not have a
      predetermined period of receptivity, but instead remained receptive until they
      received pollen. In contrast, flowering phenology did affect fruit set. Fruit set
      was most abundant when male and female flowering was most abundant. This suggests
      there was some degree of pollen limitation during the part of the flowering
      season when male flowers were scarce.

PMID- 11250824
TI  - High-temperature, acid-hydrolyzed remains of Polytrichum (Musci, Polytrichaceae)
      resemble enigmatic Silurian-Devonian tubular microfossils.
AB  - Gametophytes and sporophyte components of two species of the evolutionarily early
      divergent moss Polytrichum were separately subjected to high-temperature acid
      hydrolysis, and remains were examined by fluorescence microscopy and scanning
      electron microscopy. Remains included fragments of capsule, seta, leaves, stems,
      and calyptra. Cell walls of all remains were autofluorescent in violet and UV
      excitation, suggesting occurrence of resistant polyphenolic compounds. Calyptras
      of both species dissociated into smooth- walled, acutely branched filamentous
      associations of tubular cells with distinctively thickened cell junctions. In
      these aspects and measurements of wall dimensions made from SEMs, the hydrolysis
      resistant Polytrichum calyptra remains were similar to several tubular
      microfossils described from Silurian and Lower Devonian deposits, whose
      provenance is unknown or ascribed to fungi. Our data suggest the possibility that
      at least some ancient tubular microfossils might have originated from Polytrichum
      like early mosses. They add to increasing evidence that bryophytes left
      microfossil evidence for their presence millions of years earlier than is
      indicated by their macrofossil record.

PMID- 11250825
TI  - Fossil flowers of ericalean affinity from the Late Cretaceous of Southern Sweden.
AB  - Charcoalified fossil flowers of a new genus and species (Paradinandra suecica)
      with affinities to Ericales s.l. (sensu lato) are described from the Late
      Cretaceous (Santonian-Campanian) from Southern Sweden. The flowers are
      pentamerous, hypogynous, and actinomorphic. Aestivation of sepals and petals is
      imbricate-quincuncial. The androecium consists of an outer whorl with single
      episepalous stamens and an inner whorl with paired epipetalous stamens. Pollen is
      small and probably tricolpate. Three carpels form a syncarpous ovary with
      numerous campylotropous ovules on parietal placentae. The styles are free for
      most of their length. The structure of mature fruits and seeds is unknown. Clear
      distinction of sepals and petals, possible dehiscence of anthers by restricted
      slits, presence of a nectary, and the general floral construction (salverform
      corolla) with a canalized access to the floral center clearly indicate insect
      pollination of the fossil flowers. Comparisons with extant taxa demonstrate that
      Paradinandra suecica shares many similarities with Ericales s.l. and in
      particular with members of Ternstroemiaceae, Theaceae, and Actinidiaceae.
      However, it is neither identical to any one genus of these families nor to any of
      the previously described ericalean taxa from the Cretaceous and thus provides
      further evidence of the diversity of Cretaceous ericalean plants.

PMID- 11250826
TI  - Chromosome numbers in Chihuahuan Desert Cactaceae. III. Trans-Pecos Texas.
AB  - Chromosome numbers are reported for 112 collections of Cactaceae, including 102
      collections of Opuntia. Reports are presented for 33 species in five genera and a
      total of 36 taxa. Two specimens were sterile. Emphasis was given to the
      documentation of intraspecific ploidy-level consistencies and differences,
      because of the current poor state of knowledge about the populational integrity
      of chromosome numbers in Trans-Pecos cacti and because information about ploidy
      levels is taxonomically significant particularly in certain genera of Cactaceae.
      First reports are presented for six taxa, including Opuntia aureispina (2n = 11
      II), O. tortispina (2n = 33 II), and Ancistrocactus tobuschii (2n = 11 II).
      Chromosome numbers are now known for all but one or two of the ~104 currently
      recognized cactus taxa in Trans-Pecos Texas.

PMID- 11250827
TI  - Molecular phylogenetics of Melastomataceae and Memecylaceae: implications for
      character evolution.
AB  - Melastomataceae are among the most abundant and diversified groups of plants
      throughout the tropics, but their intrafamily relationships and morphological
      evolution are poorly understood. Here we report the results of parsimony and
      maximum likelihood (ML) analyses of cpDNA sequences from the rbcL and ndhF genes
      and the rpl16 intron, generated for eight outgroups (Crypteroniaceae,
      Alzateaceae, Rhynchocalycaceae, Oliniaceae, Penaeaceae, Myrtaceae, and
      Onagraceae) and 54 species of melastomes. The sample represents 42 of the
      family's currently recognized ~150 genera, the 13 traditional tribes, and the
      three subfamilies, Astronioideae, Melastomatoideae, and Memecyloideae (=
      Memecylaceae DC.). Parsimony and ML yield congruent topologies that place
      Memecylaceae as sister to Melastomataceae. Pternandra, a Southeast Asian genus of
      15 species of which five were sampled, is the first- branching Melastomataceae.
      This placement has low bootstrap support (72%), but agrees with morphological
      treatments that placed Pternandra in Melastomatacaeae because of its acrodromal
      leaf venation, usually ranked as a tribe or subfamily. The interxylary phloem
      islands found in Memecylaceae and Pternandra, but not most other Melastomataceae,
      likely evolved in parallel because Pternandra resembles Melastomataceae in its
      other wood characters. A newly discovered plesiomorphic character in Pternandra,
      also present in Memecylaceae, is a fibrous anther endothecium. Higher
      Melastomataceae lack an endothecium as do the closest relatives of
      Melastomataceae and Memecylaceae. The next deepest split is between Astronieae,
      with anthers opening by slits, and all remaining Melastomataceae, which have
      anthers opening by pores. Within the latter, several generic groups,
      corresponding to traditional tribes, receive solid statistical support, but
      relationships among them, with one exception, are different from anything
      predicted on the basis of morphological data. Thus, Miconieae and Merianieae are
      sister groups, and both are sister to a trichotomy of Bertolonieae, Microlicieae
      + Melastomeae, and Dissochaeteae + Blakeeae. Sonerileae/Oxysporeae are nested
      within Dissochaeteae, Rhexieae within Melastomeae, and African and Asian
      Melastomeae within neotropical Melastomeae. These findings have profound
      implications for our understanding of melastome morphological evolution (and
      biogeography), implying, for example, that berries evolved from capsules
      minimally four times, stamen connectives went from dorsally enlarged to
      basal/ventrally enlarged, and loss of an endothecium preceded poricidal
      dehiscence.

PMID- 11250828
TI  - Chromosome studies: Mexican Compositae.
AB  - Chromosome observations reported here from 70 collections representing 65 species
      from 40 genera of Compositae (mostly Heliantheae) provide taxonomically useful
      information. First counts for 28 species, including the first count for
      Psacaliopsis, may prove to be especially interesting in relation to phyletic and
      taxonomic alignments of the taxa. Of special interest among first reports is 2n =
      5 II for Stevia lita; other stevias have x = 11, 12, or 17. Thirteen of our
      counts differ from prior reports and may also be of particular interest in
      phyletic and taxonomic contexts.

PMID- 11250829
TI  - The dalbergioid legumes (Fabaceae): delimitation of a pantropical monophyletic
      clade.
AB  - A monophyletic pantropical group of papilionoid legumes, here referred to as the
      "dalbergioid" legumes, is circumscribed to include all genera previously referred
      to the tribes Aeschynomeneae and Adesmieae, the subtribe Bryinae of the
      Desmodieae, and tribe Dalbergieae except Andira, Hymenolobium, Vatairea, and
      Vataireopsis. This previously undetected group was discovered with phylogenetic
      analysis of DNA sequences from the chloroplast trnK (including matK) and trnL
      introns, and the nuclear ribosomal 5.8S and flanking internal transcribed spacers
      1 and 2. All dalbergioids belong to one of three well-supported subclades, the
      Adesmia, Dalbergia, and Pterocarpus clades. The dalbergioid clade and its three
      main subclades are cryptic in the sense that they are genetically distinct but
      poorly, if at all, distinguished by nonmolecular data. Traditionally important
      taxonomic characters, such as arborescent habit, free stamens, and lomented pods,
      do not provide support for the major clades identified by the molecular analysis.
      Short shoots, glandular-based trichomes, bilabiate calyces, and aeschynomenoid
      root nodules, in contrast, are better indicators of relationship at this
      hierarchical level. The discovery of the dalbergioid clade prompted a re-analysis
      of root nodule structure and the subsequent finding that the aeschynomenoid root
      nodule is synapomorphic for the dalbergioids.

PMID- 11250830
TI  - Molecular systematics of the Brassicaceae: evidence from coding plastidic matK
      and nuclear Chs sequences.
AB  - Phylogenetic relationships were inferred using nucleotide sequence variation of
      the nuclear-encoded chalcone synthase gene (Chs) and the chloroplast gene matK
      for members of five tribes from the family Brassicaceae to analyze tribal and
      subtribal structures. Phylogenetic trees from individual data sets are mostly in
      congruence with the results from a combined matK-Chs analysis with a total of
      2721 base pairs, but with greater resolution and higher statistical support for
      deeper branching patterns. The analysis indicates that tribes Lepidieae,
      Arabideae, and Sisymbrieae are not monophyletic. Among taxa under study four
      different lineages each were detected in tribes Arabideae and Lepidieae,
      interspersed with taxa from tribes Sisymbrieae, Hesperideae, and Brassiceae. It
      is concluded that tribe Brassiceae might be the only monophyletic group of the
      traditional tribes. From our data we estimated several divergence times for
      different lineages among cruciferous plants: 5.8 mya (million years ago) for the
      Arabidopsis-Cardaminopsis split, 20 mya for the Brassica-Arabidopsis split, and
      ~40 mya for the age of the deepest split between the most basal crucifer
      Aethionema and remaining cruciferous taxa.

PMID- 11250831
TI  - Variation in performance of the tree fern Cyathea caracasana (Cyatheaceae) across
      a successional mosaic in an Andean cloud forest.
AB  - In Andean forests, Cyathea caracasana grows across a range of successional
      habitats. This study documents variation in several measures of plant performance
      (stem growth, leaf production, leaf longevity, and spore production) in C.
      caracasana growing in open habitat, low-canopy secondary forest, and high-canopy
      secondary forest, based on 33 mo of observation. In open habitat, C. caracasana
      displayed significantly higher growth rates, leaf production rates, and leaf
      turnover than in either of the forested habitats. The highest rates of spore
      production were also observed in open-habitat individuals, with only one plant in
      the forest understory producing spores during the study. Despite low growth and
      no reproduction, I observed no mortality among ferns in the forest understory.
      These data show that C. caracasana performs best under conditions of full sun but
      can persist under the closed canopy. This suggests a life history in which
      periods of rapid growth, spore production, and recruitment in forest gaps
      alternate with low growth rate and persistence in the understory. A phylogenetic
      perspective suggests that the habitat flexibility, which might conventionally
      mark C. caracasana as a habitat generalist, is better interpreted as
      specialization for the dynamic forest in which it grows.

PMID- 11250832
TI  - Does the duration of breast feeding matter?

PMID- 11250833
TI  - Providing clean water: lessons from Bangladesh.

PMID- 11250834
TI  - Electronic publishing in science.

PMID- 11250835
TI  - Poor world health and rich world wealth.

PMID- 11250836
TI  - Obesity genes.

PMID- 11250837
TI  - What is the optimal weight for cardiovascular health?

PMID- 11250838
TI  - Use of confidential HIV data helps convict former prisoner.

PMID- 11250839
TI  - A fifth of suicides among people with mental illness are preventable.

PMID- 11250840
TI  - Whistleblower thanked but still suspended.

PMID- 11250841
TI  - Glucosamine and chondroitin may help in osteoarthritis.

PMID- 11250842
TI  - South African court battle damages drug industry's image.

PMID- 11250843
TI  - Review clears Harefield surgeons.

PMID- 11250844
TI  - Obesity drug endorsed by NICE.

PMID- 11250845
TI  - US doctors call for simpler Medicare rules.

PMID- 11250847
TI  - Deprivation and late presentation of glaucoma: case-control study.
AB  - OBJECTIVE: To identify socioeconomic risk factors for first presentation advanced
      glaucomatous visual field loss. DESIGN: Hospital based case-control study with
      prospective identification of patients. SETTING: Three hospital eye departments.
      PARTICIPANTS: Consecutive patients newly diagnosed with glaucoma (n=220). Cases
      (late presenters) were those presenting with advanced glaucoma (n=110), controls
      were those with early glaucoma (n=110). RESULTS: Median underprivileged area
      scores were higher among late presenters (29.5; interquartile range 9.0-42.2)
      than in the control group (21.3; 6.1-37.4) (P=0.035). Late presenters were more
      likely to be of lower occupational class (odds ratio adjusted for age and
      referral centre 20.1 (95% confidence interval 2.6 to 155) for group III compared
      with group I-II and 86.0 (11.0 to 673 for group IV-V compared with group I-II),
      to have no access to a car (2.2; 1.2 to 4.0), to have left full time education at
      age 14 or less (7.5; 2.3 to 24.7), and to be tenants rather than owner occupiers
      (local authority tenants 3.2; 1.7 to 5.8, private tenants 2.1; 0.7 to 5.8).
      Effects of deprivation were partly accounted for by family history of glaucoma,
      time since last visit to an optometrist, and lack of an initial diagnosis of
      glaucoma by an optometrist. CONCLUSIONS: Area and individual level deprivation
      were both associated with late presentation of glaucoma. Existing evidence shows
      that late presentation is an important risk factor for subsequent blindness.
      Deprived groups thus seem to be at greater risk of going blind from glaucoma.
      Material deprivation may be associated with more aggressive disease as well as
      later presentation.

PMID- 11250848
TI  - Duration of breast feeding and arterial distensibility in early adult life:
      population based study.
AB  - OBJECTIVES: To test the hypothesis that duration of breast feeding is related to
      changes in vascular function relevant to the development of cardiovascular
      disease. DESIGN: Population based observational study. SETTING: Cambridge.
      PARTICIPANTS: 331 adults (171 women, 160 men) aged between 20 and 28 years, born
      in Cambridge Maternity Hospital. MAIN OUTCOME MEASURES: Distensibility of
      brachial artery, type and duration of infant feeding, current lipid profile, and
      other cardiovascular risk factors. RESULTS: The longer the period of breast
      feeding the less distensible the artery wall in early adult life, with no sex
      differences (regression coefficient = -3.93 micrometer/month, 95% confidence
      interval -7.29 to -0.57, P=0.02). However, in those breast fed for less than four
      months, arterial distensibility was not significantly reduced compared with an
      exclusively formula fed group. The vascular changes observed were not explained
      by alterations in plasma cholesterol concentration in adult life. CONCLUSIONS:
      Breast feeding in infancy is related to reduced arterial function 20 years later.
      These data should not alter current recommendations in favour of breast feeding,
      which has several benefits for infant health. Further work is needed, however, to
      explore the optimal duration of breast feeding in relation to cardiovascular
      outcomes.

PMID- 11250849
TI  - Employment status and health after privatisation in white collar civil servants:
      prospective cohort study.
AB  - OBJECTIVES: To determine whether employment status after job loss due to
      privatisation influences health and use of health services and whether financial
      strain, psychosocial measures, or health related behaviours can explain any
      findings. DESIGN: Data collected before and 18 months after privatisation.
      SETTING: One department of the civil service that was sold to the private sector.
      PARTICIPANTS: 666 employees during baseline screening in the department to be
      privatised. MAIN OUTCOME MEASURES: Health and health service outcomes associated
      with insecure re-employment, permanent exit from paid employment, and
      unemployment after privatisation compared with outcomes associated with secure re
      employment. RESULTS: Insecure re-employment and unemployment were associated with
      relative increases in minor psychiatric morbidity (mean difference 1.56 (95%
      confidence intervals interval 1.0 to 2.2) and 1.25 (0.6 to 2.0) respectively) and
      having four or more consultations with a general practitioner in the past year
      (odds ratio 2.04 (1.1 to 3.8) and 2.39 (1.2 to 4.7) respectively). Health
      outcomes for respondents permanently out of paid employment closely resembled
      those in secure re-employment, except for a substantial relative increase in
      longstanding illness (2.25; 1.1 to 4.4). Financial strain and change in
      psychosocial measures and health related behaviours accounted for little of the
      observed associations. Adjustment for change in minor psychiatric morbidity
      attenuated the association between insecure re-employment or unemployment and
      general practitioner consultations by 26% and 27%, respectively. CONCLUSIONS:
      Insecure re-employment and unemployment after privatisation result in increases
      in minor psychiatric morbidity and consultations with a general practitioner,
      which are possibly due to the increased minor psychiatric morbidity.

PMID- 11250850
TI  - Cardiovascular events in users of sildenafil: results from first phase of
      prescription event monitoring in England.

PMID- 11250851
TI  - Tsp509I polymorphism in exon 2 of the glucocorticoid receptor gene in relation to
      obesity and cortisol secretion: cohort study.

PMID- 11250852
TI  - Reducing prescribing of highly anticholinergic antidepressants for elderly
      people: randomised trial of group versus individual academic detailing.
AB  - OBJECTIVE: To compare the effect of individual educational visits versus group
      visits using academic detailing to discuss prescribing of highly anticholinergic
      antidepressants in elderly people. DESIGN: Randomised controlled trial with three
      arms (individual visits, group visits, and a control arm). SETTING: Southwest
      Netherlands. PARTICIPANTS: 190 general practitioners and 37 pharmacists organised
      in 21 peer review groups were studied using a database covering all prescriptions
      to people covered by national health insurance in the area (about 240 000).
      INTERVENTION: All general practitioners and pharmacists in both intervention arms
      were offered two educational visits. For physicians in groups randomised to the
      individual visit arm, 43 of 70 general practitioners participated; in the group
      visit intervention arm, five of seven groups (41 of 52 general practitioners)
      participated. MAIN OUTCOME MEASURES: Numbers of elderly people (>/=60 years) with
      new prescriptions of highly anticholinergic antidepressants and less
      anticholinergic antidepressants. RESULTS: An intention to treat analysis found a
      26% reduction in the rate of starting highly anticholinergic antidepressants in
      elderly people (95% confidence interval -4% to 48%) in the individual
      intervention arm and 45% (8% to 67%) in the group intervention arm. The use of
      less anticholinergic antidepressants increased by 40% (6% to 83%) in the
      individual intervention arm and 29% (-7% to 79%) in the group intervention arm.
      CONCLUSIONS: Both the individual and the group visits decreased the use of highly
      anticholinergic antidepressants and increased the use of less anticholinergic
      antidepressant in elderly people. These approaches are practical means to improve
      prescribing by continuing medical education.

PMID- 11250853
TI  - Pelvic inflammatory disease.

PMID- 11250854
TI  - ABC of diseases of liver, pancreas, and biliary system. Chronic pancreatitis.

PMID- 11250855
TI  - Patient choice modules for summaries of clinical effectiveness: a proposal.

PMID- 11250856
TI  - Maintaining the dignity and autonomy of older people in the healthcare setting.

PMID- 11250857
TI  - Inferiority of calcium channel blockers to cheaper drugs. News item was
      inaccurate on at least two counts.

PMID- 11250858
TI  - Secondary prevention may help intermittent claudication.

PMID- 11250859
TI  - Inferiority of calcium channel blockers to cheaper drugs. Use of long acting
      calcium channel blockers is not deleterious in elderly hypertensive patients.

PMID- 11250860
TI  - Vision is needed to address problem of global health information.

PMID- 11250861
TI  - Registry for torsades de pointes with drug treatment exists.

PMID- 11250862
TI  - Testing night vision for driving.

PMID- 11250863
TI  - Data collection barriers can be overcome by schemes such as MEDICS.

PMID- 11250864
TI  - Judicial functions of GMC should be abolished.

PMID- 11250865
TI  - Enhanced acetylcholine release in the hippocampus of cannabinoid CB(1) receptor
      deficient mice.
AB  - We examined whether acetylcholine release in the hippocampus and striatum and
      noradrenaline release in the hippocampus is altered in CB(1) receptor-deficient
      mice. The electrically evoked tritium overflow from hippocampal slices
      preincubated with [(3)H]-choline was increased by about 100% in CB(1)(-/-)
      compared to CB(1)(+/+) mice whereas the electrically evoked tritium overflow from
      striatal slices preincubated with [(3)H]-choline and from hippocampal slices
      preincubated with [(3)H]-noradrenaline did not differ. The cannabinoid receptor
      agonist, WIN 55,212-2, inhibited, and the CB(1) receptor antagonist, SR 141716,
      facilitated, the evoked tritium overflow from hippocampal slices (preincubated
      with [(3)H]-choline) from CB(1)(+/+) as opposed to CB(1)(-/-) mice. Both drugs
      did not affect the evoked tritium overflow from striatal slices (preincubated
      with [(3)H]-choline) and from hippocampal slices (preincubated with [(3)H]
      noradrenaline) from CB(1)(+/+) and CB(1)(-/-) mice. The selective increase in
      acetylcholine release in CB(1)(-/-) mice may indicate that the presynaptic CB(1)
      receptors on the cholinergic neurones of the mouse hippocampus are tonically
      activated and/or constitutively active in vivo.

PMID- 11250866
TI  - Nociceptin inhibits cough in the guinea-pig by activation of ORL(1) receptors.
AB  - We studied the central and peripheral antitussive effect of ORL(1) receptor
      activation with nociceptin/orphanin FQ in conscious guinea-pigs. In guinea-pig
      cough studies, nociceptin/orphanin FQ (10, 30, and 90 microg) given directly into
      the CNS by an intracerebroventricular (i.c.v.) route inhibited cough elicited by
      capsaicin exposure by approximately 23, 29 and 52%, respectively. The antitussive
      activity of nociceptin/orphanin FQ (90 microg, i.c.v.) was blocked by the
      selective ORL(1) antagonist [Phe(1)gamma(CH(2)-NH)Gly(2)]nociceptin-(1-13)-NH(2)
      (180 microg, i.c.v.) and J113397 (10 mg kg(-1), i.p.) but not by the opioid
      antagonist, naltrexone (3 mg kg(-1), i.p.). Furthermore, intravenous (i.v.)
      nociceptin/orphanin FQ (1.0 and 3.0 mg kg(-1)) also inhibited cough approximately
      by 25 and 42%, respectively. These findings indicate that selective ORL(1)
      agonists display the potential to inhibit cough by both a central and peripheral
      mechanism, and potentially represent a novel therapeutic approach for the
      treatment of cough.

PMID- 11250867
TI  - SB-334867-A: the first selective orexin-1 receptor antagonist.
AB  - The pharmacology of various peptide and non-peptide ligands was studied in
      Chinese hamster ovary (CHO) cells stably expressing human orexin-1 (OX(1)) or
      orexin-2 (OX(2)) receptors by measuring intracellular calcium ([Ca(2+)](i)) using
      Fluo-3AM. Orexin-A and orexin-B increased [Ca(2+)](i) in CHO-OX(1)
      (pEC(50)=8.38+/-0.04 and 7.26+/-0.05 respectively, n=12) and CHO-OX(2)
      (pEC(50)=8.20+/-0.03 and 8.26+/-0.04 respectively, n=8) cells. However,
      neuropeptide Y and secretin (10 pM - 10 microM) displayed neither agonist nor
      antagonist properties in either cell-line. SB-334867-A (1-(2-Methyylbenzoxanzol-6
      yl)-3-[1,5]naphthyridin-4-yl-urea hydrochloride) inhibited the orexin-A (10 nM)
      and orexin-B (100 nM)-induced calcium responses (pK(B)=7.27+/-0.04 and 7.23+/
      0.03 respectively, n=8), but had no effect on the UTP (3 microM)-induced calcium
      response in CHO-OX(1) cells. SB-334867-A (10 microM) also inhibited OX(2)
      mediated calcium responses (32.7+/-1.9% versus orexin-A). SB-334867-A was devoid
      of agonist properties in either cell-line. In conclusion, SB-334867-A is a non
      peptide OX(1) selective receptor antagonist.

PMID- 11250868
TI  - HMG-CoA reductase inhibitors and P-glycoprotein modulation.
AB  - 1. Five 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors
      (statins), (e.g. atorvastatin, fluvastatin, lovastatin, pravastatin and
      simvastatin), were investigated for their ability to reverse P-glycoprotein (P
      gp) mediated rhodamine 123 (R123) transport in a murine monocytic leukaemia cell
      line that over-expresses the multi-drug resistance protein 1a/b (mdr1a/1b). 2. P
      gp modulation was studied by a fluorimetric assay and confocal microscopy by
      means of R123 efflux and uptake experiments, respectively. 3. Atorvastatin acid,
      methyl ester and lactone, lovastatin lactone and simvastatin lactone inhibited
      R123 transport in a concentration-dependent manner. Lovastatin acid, simvastatin
      acid, fluvastatin and pravastatin did not show a significant inhibition of the
      R123 transport in our cell system. Atorvastatin methyl ester and lactone showed
      the highest affinities for P-gp and results were comparable for both methods. 4.
      In conclusion, monitoring of R123 transport in living cells by confocal
      microscopy in addition to fluorimetric assay is a sensitive tool to study P-gp
      affinity in drug screening that is especially useful for early phases of drug
      development.

PMID- 11250869
TI  - The transport activity of the human cationic amino acid transporter hCAT-1 is
      downregulated by activation of protein kinase C.
AB  - 1. The human cationic amino acid transporter hCAT-1 contains several consensus
      sequences for phosphorylation by protein kinase C (PKC). This study investigates
      the effect of PKC activation on hCAT-1-mediated transport. 2. When expressed in
      Xenopus laevis oocytes, hCAT-1-mediated L-arginine transport was reduced to 44+/
      3% after a 30 min treatment of the oocytes with 100 nM phorbol-12-myristate-13
      acetate (PMA). 4 alpha-phorbol-12,13-didecanoate (4 alpha-PDD, 100 nM) had no
      effect. 3. In EA.hy926 endothelial cells, maximal inhibition of hCAT-1-mediated L
      arginine transport (to 3 -- 11% of control) was observed after treatment of the
      cells with 100 nM PMA for 4 h. A 20 -- 30 h exposure of the cells to 100 nM PMA
      led to the recovery of the L-arginine uptake rate that was now resistant to a
      second application of PMA. Phorbol-12,13-dibutyrate had similar effects as PMA,
      whereas 4 alpha-PDD had no effect. One microM bisindolylmaleimide I reduced the
      PMA effect significantly. 4. Interestingly, a 4 h treatment with 100 nM PMA
      increased the expression of hCAT-1 mRNA 3 -- 5 fold. hCAT-1 protein levels were
      unchanged for up to 4 h after PMA treatment and then increased slightly between 8
      -- 28 h. 5. It is concluded that PMA downregulates the intrinsic activity of hCAT
      1 by a pathway involving protein kinase C.

PMID- 11250870
TI  - Nerve evoked P2X receptor contractions of rat mesenteric arteries; dependence on
      vessel size and lack of role of L-type calcium channels and calcium induced
      calcium release.
AB  - 1. Contractile responses to short trains of nerve stimulation have been
      characterized in small, medium and large arteries from the rat mesenteric
      circulation (5th - 6th, 2nd - 3rd and 1st order, respectively). In addition,
      sources of calcium for smooth muscle contraction have been investigated. 2. Nerve
      stimulation (10 pulses at 10 Hz) evoked reproducible contractions. The P2
      receptor antagonist suramin (100 microM) reduced constrictions by 65.3+/-7.4,
      82.7+/-3.3 and 3.1+/-6.1% in small, medium and large arteries respectively. The
      alpha-adrenoceptor antagonist prazosin (0.1 microM) reduced responses by 32.6+/
      2.6, 27.0+/-1.5 and 97.0+/-1.9% respectively. 3. The L-type calcium channel
      antagonist nifedipine (1 microM) reduced nerve-evoked contractions by 2.8+/-3.3,
      10.0+/-3.7 and 13.5+/-2.7% in small, medium and large arteries respectively. When
      the adrenergic component of contraction was blocked by prazosin (0.1 microM)
      nifedipine reduced responses by 4.6+/-7.9, 14.3+/-2.0 and 3.0+/-1.9%
      respectively. Contractile responses to exogenous alpha,beta-meATP were unaffected
      by the depletion of calcium stores with cyclopiazonic acid (30 microM). This
      indicates that mobilization of calcium from internal stores is not required for
      P2X receptor mediated smooth muscle contraction. We conclude that for neurogenic
      responses, the P2X receptor mediated component of constriction dominates in small
      mesenteric arteries (3rd -- 6th order) while in large arteries (1st order)
      noradrenaline mediates contraction. For P2X receptor mediated responses all the
      calcium required for smooth muscle contraction enters the cell directly through
      P2X receptor channels.

PMID- 11250871
TI  - Investigation of mechanisms that mediate reactive hyperaemia in guinea-pig
      hearts: role of K(ATP) channels, adenosine, nitric oxide and prostaglandins.
AB  - 1. Reactive hyperaemia is a transient vasodilatation following a brief ischaemic
      period. ATP-dependent K(+) (K(ATP)) channels may be important in mediating this
      response, however it is unclear whether mitochondrial K(ATP) channels contribute
      to this in the heart. 2. We examined the involvement of K(ATP) channels and the
      relative role of mitochondrial channels as mediators of coronary reactive
      hyperaemia and compared them to mechanisms involving NO, prostaglandins and
      adenosine in the guinea-pig isolated heart. 3. Reactive hyperaemic vasodilatation
      (peak vasodilator response and flow debt repayment) were assessed after global
      zero-flow ischaemia (5 -- 120 s) in the presence of nitro-L-arginine methyl ester
      (L-NAME, 10(-5) M, n=9), 8-phenyltheophylline (8-PT, 10(-6) M, n=12) and
      indomethacin (10(-5) M, n=12). 4. Glibenclamide (10(-6) M, n=12) a non-selective
      K(ATP) channel inhibitor and 5-hydroxy-decanoic acid (5-HD, 10(-4) M, n=10) a
      selective mitochondrial K(ATP) channel inhibitor were also used. The specificity
      of the effects of glibenclamide and 5-HD (n=6 each) were confirmed using
      pinacidil (38 nmol -- 10 micromol) and diazoxide (42 nmol -- 2 micromol).
      Glibenclamide was most effective in blocking the hyperaemic response (by 87%,
      P<0.001) although 5-HD and 8-PT also had a marked effect (40% inhibition, P<0.001
      and 32%, P<0.001, respectively). L-NAME and indomethacin had little effect. 5.
      Perfusion with L-NAME and glibenclamide significantly reduced baseline coronary
      flow (22%, P<0.01 and 33%, P<0.01) while 8-PT, indomethacin and 5-HD had no
      effect. 6. K(ATP) channels are the major mediators of the coronary reactive
      hyperaemic response in the guinea-pig. Although mitochondrial K(ATP) channels
      contribute, they appear less important than sarcolemmal channels.

PMID- 11250873
TI  - Protective effect of a PAR2-activating peptide on histamine-induced
      bronchoconstriction in guinea-pig.
AB  - 1. Protease activated receptor-2 (PAR2) is a seven transmembrane domain G protein
      coupled receptor proteolytically activated. PAR2, together with other PARs, can
      be also activated by peptides mimicking the sequence of the receptor tethered
      ligand. We have evaluated the effect of systemic administration of a peptide
      activating PAR2 (PAR2-AP, SLIGRL) on histamine-induced increase in lung
      resistances in the guinea-pig. 2. Intravenous administration of PAR2-AP (1 mg kg(
      1)) significantly inhibited histamine-induced increase in lung resistance in a
      time-dependent fashion that was not abolished by indomethacin or vagotomy. 3.
      Bronchoprotective effect of PAR2-AP was not reversed by the cyclo-oxygenase
      inhibitor, indomethacin, the nitric oxide synthetase inhibitor, L-NAME, nor by
      the non-selective beta-antagonist, propranolol. 4. Indomethacin augmented the
      bronchoconstriction to histamine which was inhibited by PAR2-AP. Furthermore, in
      vagotomized animals, the bronchial hyper-responsiveness to histamine was
      significantly reduced, and in these circumstances, PAR2-AP still retained the
      capacity to provide bronchoprotection against histamine. 5. PAR2-AP also produced
      a modest reduction in histamine-induced protein leakage in trachea and upper
      bronchi. 6. Our results indicated that PAR2 might have a bronchoprotective role
      in the guinea-pig in vivo independent of prostaglandin or nitric oxide release.

PMID- 11250872
TI  - Dual effects of muscarinic M(2) acetylcholine receptors on the synthesis of
      cyclic AMP in CHO cells: dependence on time, receptor density and receptor
      agonists.
AB  - 1. Muscarinic M(2) receptors normally inhibit the production of cyclic AMP via
      G(i) proteins, but a stimulatory component occurs in their effect at high agonist
      concentrations, believed to be based on the activation of G(s) proteins. We
      investigated the conditions which determine the occurrence and extent of the
      stimulatory component in CHO cells stably expressing muscarinic M(2) receptors.
      2. Biphasic concentration-response curves (decline followed by return towards
      control values) were obtained after 10 min incubation with carbachol,
      oxotremorine-M, acetylcholine, arecoline and arecaidine propargyl ester, but the
      upward phase was missing with oxotremorine, methylfurmethide, furmethide and
      pentylthio-TZTP. Shortening the incubation favoured the occurrence of the
      stimulatory component. Carbachol (1 mM) and oxotremorine-M (1 mM) brought about
      net stimulation (above 100% of control) of cyclic AMP synthesis during 2 min
      incubations. The stimulatory components disappeared after the density of
      receptors had been lowered with oxyphenonium mustard. 3. All agonists stimulated
      the synthesis of cyclic AMP in cells pretreated with pertussis toxin. 4. Most
      differences between agonists regarding the stimulatory component of their effect
      on cyclic AMP synthesis could be explained by differences in their efficacy and
      the induced receptor internalization. 5. We propose that the G(s)-mediated
      stimulatory component of the effect of muscarinic M(2) receptors on cyclic AMP
      synthesis only occurs if the density of activated receptors is high enough to
      saturate the G(i) proteins and proportionate to the receptors' low affinity for
      the G(s) proteins. It tends to be abolished by receptor internalization.

PMID- 11250874
TI  - Mechanism of CGRP-induced relaxation in rat intramural coronary arteries.
AB  - 1. This study investigates the mechanism of CGRP-induced relaxation in intramural
      coronary arteries by determining the effect of CGRP on cytosolic Ca(2+)
      concentration ([Ca(2+)](i)) using FURA-2 technique. 2. CGRP concentration
      dependently (10 pM - 100 nM) decreased the [Ca(2+)](i) and tension of coronary
      arteries precontracted with either U46619 or BAY K 8644, and also of resting
      coronary arteries in PSS. In 36 mM K(+)-depolarized arteries, CGRP reduced only
      the tension without affecting the [Ca(2+)](i). 3. In 300 nM U46619- precontracted
      arteries, pretreatment with 10 microM thapsigargin significantly (P<0.05)
      attenuated the CGRP-induced reduction in the tension (but not [Ca(2+)](i)). 4. In
      300 nM U46619-precontracted arteries, pretreatment with either 100 nM
      charybdotoxin or 100 nM iberiotoxin or 10 nM felodipine significantly (P<0.05)
      attenuated the CGRP-induced reduction in both [Ca(2+)](i) and tension. In
      contrast, 1 microM glibenclamide did not affect the CGRP-induced responses in
      these coronary arteries. 5. In resting coronary arteries, only pretreatment with
      the combination of 1 microM glibenclamide and 100 nM charybdotoxin attenuated the
      CGRP-induced decrease in the [Ca(2+)](i) and tension, suggesting a different
      mechanism of action for CGRP in resting coronary arteries. 6. We conclude that
      CGRP relaxes precontracted rat coronary arteries via three mechanisms: (1) a
      decrease in [Ca(2+)](i) by inhibiting the Ca(2+) influx through membrane
      hyperpolarization mediated partly by activation of the large conductance Ca(2+)
      activated potassium channels, (2) a decrease in [Ca(2+)](i) presumably by
      sequestrating cytosolic Ca(2+) into thapsigargin-sensitive Ca(2+) storage sites
      and (3) a decrease in the Ca(2+)-sensitivity of the contractile apparatus. In
      resting coronary arteries, however, there seems to be an interplay between
      different types of K(+) channels.

PMID- 11250876
TI  - [(125)I]-(Pyr(1))Apelin-13 is a novel radioligand for localizing the APJ orphan
      receptor in human and rat tissues with evidence for a vasoconstrictor role in
      man.
AB  - 1. We have determined the binding characteristics of [(125)I]-(Pyr(1))Apelin-13,
      a putative ligand for the APJ orphan receptor in human cardiovascular and rat
      tissue and investigated the functional properties of (Pyr(1))Apelin-13 in human
      saphenous vein. 2. The binding of [(125)I]-(Pyr(1))Apelin-13 to sections of human
      heart tissue was time dependent and rapid at 23 degrees C. Data were fitted to a
      single site model with an association rate constant (k(obs)) of 0.115 min(-1).
      [(125)I]-(Pyr(1))Apelin-13 also dissociated from a single site with a
      dissociation rate constant of 0.0105 min(-1). 3. In saturation binding
      experiments [(125)I]-(Pyr(1))Apelin-13 bound to human left ventricle with a K(D)
      value of 0.35+/-0.08 nM, B(max) of 4.3+/-0.9 fmol mg(-1) protein with a Hill
      slope of 0.97+/-0.04 and to the right atria with a K(D) of 0.33+/-0.09 nM, B(max)
      of 3.1+/-0.6 fmol mg(-1) protein and a Hill slope of 0.93+/-0.05. 4. [(125)I]
      (Pyr(1))Apelin-13 binding sites were localized using autoradiography to human
      cardiovascular tissue, including coronary artery, aorta and saphenous vein
      grafts. In rat tissue a high density of receptors were localized to the molecular
      layer of the rat cerebellum, rat lung, rat heart and low levels in the rat kidney
      cortex. 2. (Pyr(1))Apelin-13 potently contracted human saphenous vein with a
      pD(2) value of 8.4+/-0.2 (n=8). The maximum response elicited by the peptide was
      22.6+/-6% of 100 mM KCl. 6. We provide the first evidence of APJ receptor
      expression, relative densities and functional properties of (Pyr(1))Apelin-13 in
      human cardiovascular tissue.

PMID- 11250875
TI  - GLC-3: a novel fipronil and BIDN-sensitive, but picrotoxinin-insensitive, L
      glutamate-gated chloride channel subunit from Caenorhabditis elegans.
AB  - 1. We report the cloning and expression of a novel Caenorhabditis elegans
      polypeptide, GLC-3, with high sequence identity to previously cloned L-glutamate
      gated chloride channel subunits from nematodes and insects. 2. Expression of glc
      3 cRNA in XENOPUS oocytes resulted in the formation of homo-oligomeric L
      glutamate-gated chloride channels with robust and rapidly desensitizing currents,
      an EC(50) of 1.9+/-0.03 mM and a Hill coefficient of 1.5+/-0.1. GABA, glycine,
      histamine and NMDA all failed to activate the GLC-3 homo-oligomer at
      concentrations of 1 mM. The anthelminthic, ivermectin, directly and irreversibly
      activated the L-glutamate-gated channel with an EC(50) of 0.4+/-0.02 microM. 3.
      The GLC-3 channels were selective for chloride ions, as shown by the shift in the
      reversal potential for L-glutamate-gated currents after the reduction of external
      Cl(-) from 107.6 to 62.5 mM. 4. Picrotoxinin failed to inhibit L-glutamate
      agonist responses at concentrations up to 1 mM. The polycyclic dinitrile, 3,3-bis
      trifluoromethyl-bicyclo[2,2,1]heptane-2,2-dicarbonitrile (BIDN), completely
      blocked L-glutamate-induced chloride currents recorded from oocytes expressing
      GLC-3 with an IC(50) of 0.2+/-0.07 microM. The phenylpyrazole insecticide,
      fipronil, reversibly inhibited L-glutamate-gated currents recorded from the GLC-3
      receptor with an IC(50) of 11.5+/-0.11 microM. 5. In this study, we detail the
      unusual antagonist pharmacology of a new GluCl subunit from C. elegans. Unlike
      all other native and recombinant nematode GluCl reported to date, the GLC-3
      receptor is insensitive to picrotoxinin, but is sensitive to two other channel
      blockers, BIDN and fipronil. Further study of this receptor may provide insights
      into the molecular basis of non-competitive antagonism by these compounds.

PMID- 11250877
TI  - Chronic systemic administration of salmeterol to rats promotes pulmonary beta(2)
      adrenoceptor desensitization and down-regulation of G(s alpha).
AB  - 1. The aim of the present study was to examine the effects of chronic infusion of
      the long-acting agonist salmeterol on pulmonary beta(2)-adrenoceptor function in
      Sprague-Dawley rats in vivo and to elucidate the molecular basis of any altered
      state. 2. Systemic administration of rats with salmeterol for 7 days compromised
      the ability of salmeterol and prostaglandin E(2) (PGE(2)), given acutely by the
      intravenous route, to protect against ACh-induced bronchoconstriction when
      compared to rats treated identically with vehicle. 3. beta(1)- and beta(2)
      adrenoceptor density was significantly reduced in lung membranes harvested from
      salmeterol-treated animals, which was associated with impaired salmeterol- and
      PGE(2)-induced cyclic AMP accumulation ex vivo. 4. Three variants of G(s alpha)
      that migrated as 42, 44 and 52 kDa peptides on SDS polyacrylamide gels were
      detected in lung membranes prepared from both groups of rats but the intensity of
      each isoform was markedly reduced in rats that received salmeterol. 5. The
      activity of cytosolic, but not membrane-associated, G-protein receptor-coupled
      kinase was elevated in the lung of salmeterol-treated rats when compared to
      vehicle-treated animals. 6. The ability of salmeterol, administered systemically,
      to protect the airways of untreated rats against ACh-induced bronchoconstriction
      was short-acting (t(off) approximately 45 min), which contrasts with its long
      acting nature when given to asthmatic subjects by inhalation. 7. These results
      indicate that chronic treatment of rats with salmeterol results in heterologous
      desensitization of pulmonary G(s)-coupled receptors. In light of previous data
      obtained in rats treated chronically with salbutamol, we propose that a primary
      mechanism responsible for this effect is a reduction in membrane-associated G(s
      alpha). The short-acting nature of salmeterol, when administered systemically,
      and the reduction in beta-adrenoceptor number may be due to metabolism to a
      biologically-active, short-acting and non-selective beta-adrenoceptor agonist.

PMID- 11250878
TI  - Role of the epithelium in opposing H(2)O(2)-induced modulation of acetylcholine
      induced contractions in rabbit intrapulmonary bronchiole.
AB  - 1. The role played by the epithelium in H(2)O(2)-induced modulation of the
      mechanical responses induced by acetylcholine (ACh) in rabbit intrapulmonary
      bronchioles was investigated in epithelium-intact and -denuded strips. 2. When
      ACh (3 microM) was applied intermittently, H(2)O(2) (30 microM) enhanced the ACh
      induced contractions in epithelium-intact strips. In contrast, in epithelium
      denuded strips H(2)O(2) (30 microM) inhibited such contractions. At higher
      concentrations, H(2)O(2) concentration-dependently attenuated the ACh-induced
      contractions in both epithelium-intact and -denuded strips, its action being more
      potent in the latter strips than in the former. 3. Diclofenac (a cyclo-oxygenase
      inhibitor; 3 microM) reduced the H(2)O(2)-induced enhancement of ACh-contractions
      in epithelium-intact strips but had no effect on the H(2)O(2)-induced inhibition
      in epithelium-denuded strips. N(G)-nitro-L-arginine did not alter the effect of
      H(2)O(2) on ACh-induced contractions in epithelium-intact strips. 4. Catalase
      (500 u ml(-1)) completely blocked both H(2)O(2)-induced effects on ACh
      contractions (enhancement and inhibition). Neither superoxide dismutase (200 u
      ml(-1)) nor deferoxamine (0.5 mM) had any effect on H(2)O(2)-induced inhibition
      in epithelium-denuded strips. 5. Aminotriazole (an inhibitor of catalase; 50 mM)
      significantly potentiated the H(2)O(2)-induced inhibition of ACh-contractions in
      epithelium-intact strips but not in epithelium-denuded strips. 6. The density
      ratio for catalase (epithelium-intact over -denuded strips) analysed by Western
      blot was about 2.1, suggesting that epithelium contains more catalase than smooth
      muscle. 7. It is concluded that in rabbit intrapulmonary bronchioles, H(2)O(2)
      has dual actions on ACh-contractions. It is suggested that the epithelium may act
      as a powerful biochemical barrier via both the action of catalase (scavenging
      H(2)O(2)) and the release of bronchoconstrictor prostaglandins, thus attenuating
      the H(2)O(2)-induced modulation of ACh-contractions.

PMID- 11250879
TI  - Pharmacological analysis of cannabinoid receptor activity in the rat vas
      deferens.
AB  - 1. The interaction between the cannabinoid agonists, WIN 55,212-2 or CP 55,940
      with the CB(1) receptor-selective antagonists, SR141716A or LY320135 was
      investigated using the rat electrically-stimulated vas deferens bioassay. 2.
      Tissues were stimulated by single-field pulses (150 V, 0.5 ms) delivered every 30
      mins. In the presence of nifedipine (3 microM), agonists elicited a concentration
      dependent inhibition of the contractile response, with pEC(50) values of 7.93 and
      6.84 for WIN 55,212-2 and CP 55,940, respectively. 3. SR141716A and LY320135
      caused parallel dextral displacements of the agonist concentration-response
      curves. However, the shift of the agonist curves by either antagonist was
      accompanied by a concentration-dependent enhancement of basal (agonist
      independent) tissue contraction. 4. Addition of the amidase inhibitor,
      phenylmethylsulphonylfluoride (200 microM), resulted in a significant reduction
      of the basal twitch response, an effect consistent with the presence of tonic
      receptor activation mediated by the endogenous cannabinoid, anandamide. 5. In
      light of these findings, we propose a theoretical model of competitive agonist
      antagonist interaction in the presence of endogenous agonist tone that was used
      to derive an optimized analytical approach for the determination of antagonist
      potency estimates under conditions of tonic receptor activation. 6. This approach
      yielded pK(B) estimates for SR141716A and LY320135 that were in good agreement
      with their activity at cannabinoid CB(1) receptors. 7. It is concluded that the
      rat vas deferens contains prejunctional cannabinoid CB(1) receptors that are
      under tonic activation from endogenous substances; under these conditions our
      analytical approach is preferable to the standard methods for the determination
      of antagonist potency.

PMID- 11250880
TI  - The role of several alpha(1)- and alpha(2)-adrenoceptor subtypes mediating
      vasoconstriction in the canine external carotid circulation.
AB  - 1. It has recently been shown that both alpha(1)- and alpha(2)-adrenoceptors
      mediate vasoconstriction in the canine external carotid circulation. The present
      study set out to identify the specific subtypes (alpha(1A), alpha(1B) and
      alpha(1D) as well as alpha(2A), alpha(2B) and alpha(2C)) mediating the above
      response. 2. Consecutive 1 min intracarotid infusions of phenylephrine (alpha(1)
      adrenoceptor agonist) and BHT933 (alpha(2)-adrenoceptor agonist) produced dose
      dependent decreases in external carotid blood flow, without affecting mean
      arterial blood pressure or heart rate. 3. The responses to phenylephrine were
      selectively antagonized by the antagonists, 5-methylurapidil (alpha(1A)) or
      BMY7378 (alpha(1D)), but not by L-765,314 (alpha(1B)), BRL44408 (alpha(2A)),
      imiloxan (alpha(2B)) or MK912 (alpha(2C)). In contrast, only BRL44408 or MK912
      affected the responses to BHT933. 4. The above results support our contention
      that mainly the alpha(1A), alpha(1D), alpha(2A) and alpha(2C)-adrenoceptor
      subtypes mediate vasoconstriction in the canine external carotid circulation.

PMID- 11250881
TI  - Disturbance of peristalsis in the guinea-pig isolated small intestine by
      indomethacin, but not cyclo-oxygenase isoform-selective inhibitors.
AB  - 1. Since the cyclo-oxygenase (COX) isoform-nonselective inhibitor indomethacin is
      known to modify intestinal motility, we analysed the effects of COX-1 and COX-2
      inhibition on intestinal peristalsis. 2. Peristalsis in isolated segments of the
      guinea-pig small intestine was triggered by a rise of the intraluminal pressure
      and recorded via the pressure changes associated with peristalsis. 3. The COX-1
      inhibitor SC-560, the COX-2 inhibitor NS-398 (both at 0.1 -- 1 microM) and the
      isoform-nonselective inhibitors flurbiprofen (0.01 - 10 microM) and piroxicam
      (0.1 - 50 microM) were without major influence on peristalsis, whereas
      indomethacin and etodolac (0.1 -- 10 microM) disturbed the regularity of
      peristalsis by causing nonpropulsive circular muscle contractions. 4.
      Radioimmunoassay measurements showed that SC-560, NS-398, indomethacin and
      etodolac (each at 1 microM) suppressed the release of 6-keto-prostaglandin F(1
      alpha) (6-keto-PGF(1 alpha)) from the intestinal segments. 5. Reverse
      transcription - polymerase chain reaction tests revealed that, relative to
      glyceraldehyde-3 phosphate dehydrogenase ribonucleic acid, the expression of COX
      1 mRNA increased by a factor of 2.0 whereas that of COX-2 mRNA rose by a factor
      of 7.9 during the 2 h experimental period. 6. Pharmacological experiments
      indicated that the action of indomethacin to disturb intestinal peristalsis was
      unrelated to inhibition of L-type calcium channels, adenosine triphosphate
      sensitive potassium channels or phosphodiesterase type IV. 7. These results show
      that selective inhibition of COX-1 and COX-2 does not grossly alter peristaltic
      motor activity in the guinea-pig isolated small intestine and that the effect of
      indomethacin to disturb the regular pattern of propulsive motility in this
      species is unrelated to COX inhibition.

PMID- 11250884
TI  - Effects of some sterically hindered phenols on whole-cell Ca(2+) current of
      guinea-pig gastric fundus smooth muscle cells.
AB  - 1. The aim of the present study was to investigate the effects of extracellular
      application of some sterically-hindered phenols, namely 3-t-butyl-4
      hydroxyanisole (BHA), 3,5-di-t-butyl-4-hydroxyanisole (DTBHA) and the dimer of
      BHA, 2,2'-dihydroxy-3,3'-di-t-butyl-5,5'-dimethoxydiphenyl (DIBHA), on the whole
      cell Ca(2+) current (I(Ca)) of freshly isolated smooth muscle cells from the
      guinea-pig gastric fundus, in the presence of a range of Ca(2+) concentrations (1
      -- 5 mM) using the patch-clamp technique. The influx of Ca(2+) had
      characteristics of L-type I(Ca) (I(Ca(L))). 2. BHA as well as DTBHA inhibited
      I(Ca(L)) in a concentration-dependent manner, during depolarization to 10 mV from
      a holding potential of -50 mV. Bath application of BHA (50 microM) and DTBHA (30
      microM) decreased I(Ca(L)) by 48.9% and 45.2%, respectively. This inhibition was
      only partially reversible. In contrast, DIBHA (up to 50 microM) was devoided of
      effects on I(Ca(L)). 3. BHA inhibition of I(Ca(L)) was voltage-dependent and
      inversely related to the external concentration of Ca(2+). On the other hand,
      DTBHA inhibition was only voltage-dependent. 4. BHA and DTBHA shifted the voltage
      range of the steady-state inactivation curve to more negative potentials by 8 mV
      at the mid-potential of the curve, without affecting the activation curve.
      Furthermore, BHA and DTBHA did not modify the time-course of the current decay.
      5. We conclude that the inhibition of I(Ca(L)) by BHA and DTBHA is qualitatively
      similar to that of a Ca(2+) channel blocker and is characterized by the
      stabilizing effect of the inactivated state of the channel.

PMID- 11250882
TI  - Pharmacokinetics of pefloxacin and its interaction with cyclosporin A, a P
      glycoprotein modulator, in rat blood, brain and bile, using simultaneous
      microdialysis.
AB  - 1. In vivo microdialysis with HPLC was used to investigate the pharmacokinetics
      of pefloxacin and its interaction with cyclosporin A. Microdialysis probes were
      inserted into the jugular vein/right atrium, the striatum and the bile duct of
      male Sprague-Dawley rats. Biological fluid sampling thereby allowed the
      simultaneous determination of pefloxacin levels in blood, brain and bile. 2.
      Following pefloxacin administration, the brain-to-blood coefficient of
      distribution was 0.036. This was calculated by dividing the area under the
      concentration curve (AUC) of pefloxacin in brain by its AUC in blood
      (k=AUC(brain)/AUC(blood)). 3. When the P-glycoprotein cyclosporin A (10 mg kg(
      1)) was co-administered with pefloxacin (10 mg kg(-1)), the AUC and the mean
      residence time in rat blood did not differ significantly (P>0.05). Similarly, the
      pharmacokinetics of pefloxacin in rat brain was not affected by the presence of
      cyclosporin A. 4. The AUC of unbound pefloxacin in bile was significantly greater
      than that in blood. The disposition of pefloxacin in rat bile shows a slow
      elimination phase following a peak concentration 30 min after pefloxacin
      administration (10 mg kg(-1), i.v.). The bile-to-blood coefficient of
      distribution (k=AUC(bile)/AUC(blood)) was 1.53. 5. The results indicated that
      pefloxacin was able to penetrate the blood-brain barrier and that the
      concentration in bile was greater than that in the blood, suggesting active
      biliary excretion of pefloxacin. Current data obtained from rats show no
      significant impact of cyclosporin A on the pharmacokinetics of pefloxacin in rat
      blood and brain when administered by concomitant i.v. bolus.

PMID- 11250885
TI  - Morphological and functional in vitro and in vivo characterization of the mouse
      corpus cavernosum.
AB  - 1. In normal mice, the distribution of adrenergic, cholinergic, some peptidergic,
      and neuronal nitric oxide synthase (nNOS)-containing nerves were investigated.
      Functional in vitro correlates were obtained. An in vivo model was developed in
      which erectile haemodynamics in response to drugs or nerve-stimulation were
      studied. 2. Immunoreactivities for vesicular acetylcholine transporter protein
      (VAChT), nNOS-, and vasoactive intestinal polypeptide (VIP), co-existed in nerve
      fibres and terminal varicosities. Immunoreactivities for neuropeptide Y (NPY) and
      tyrosine hydroxylase (TH) were found in the same nerve structures. 3. Chemical
      sympathectomy abolished TH- and NPY-IR nerve structures in cavernous smooth
      muscle bundles. The distribution of calcitonin gene-related peptide (CGRP)-, nNOS
      , VAChT- and VIP-IR nerve structures was unchanged. 4. In endothelial cells of
      the central and helicine arteries, veins and venules, intense immunoreactivity
      for endothelial NOS (eNOS) was observed. No distinct eNOS-IR cells were found
      lining the cavernous sinusoids. 5. In vitro, nerve-induced relaxations were
      verified, and endothelial NO/cyclic GMP-mediated relaxant responses were
      established. VIP and CGRP had small relaxant effects. A functioning adenylate
      cyclase/cyclic AMP pathway was confirmed. 6. Neuronal excitatory responses were
      abolished by prazosin, or forskolin. VIP and CGRP counteracted contractions,
      whereas NPY and scopolamine enhanced excitatory responses. 7. In vivo, erectile
      responses were significantly attenuated by L-NAME (50 mg kg(-1)) and facilitated
      by sildenafil (200 microg kg(-1)). 8. It is concluded that the mouse is a
      suitable model for studies of erectile mechanisms in vitro and in vivo.

PMID- 11250883
TI  - Inhibitory effect of 2,3-butanedione monoxime (BDM) on Na(+)/Ca(2+) exchange
      current in guinea-pig cardiac ventricular myocytes.
AB  - 1. The effect of 2,3-butanedione monoxime (BDM), a 'chemical phosphatase', on
      Na(+)/Ca(2+) exchange current (I(NCX)) was investigated using the whole-cell
      voltage-clamp technique in single guinea-pig cardiac ventricular myocytes and in
      CCL39 fibroblast cells expressing canine NCX1. 2. I(NCX) was identified as a
      current sensitive to KB-R7943, a relatively selective NCX inhibitor, at 140 mM
      Na(+) and 2 mM Ca(2+) in the external solution and 20 mM Na(+) and 433 nM free
      Ca(2+) in the pipette solution. 3. In guinea-pig ventricular cells, BDM inhibited
      I(NCX) in a concentration-dependent manner. The IC(50) value was 2.4 mM with a
      Hill coefficients of 1. The average time for 50% inhibition by 10 mM BDM was
      124+/-31 s (n=5). 4. The effect of BDM was not affected by 1 microM okadaic acid
      in the pipette solution, indicating that the inhibition was not via activation of
      okadaic acid-sensitive protein phosphatases. 5. Intracellular trypsin treatment
      via the pipette solution significantly suppressed the inhibitory effect of BDM,
      implicating an intracellular site of action of BDM. 6. PAM (pralidoxime), another
      oxime compound, also inhibited I(NCX) in a manner similar to BDM. 7. Isoprenaline
      at 50 microM and phorbol 12-myristate 13-acetate (PMA) at 8 microM did not
      reverse the inhibition of I(NCX) by BDM. 8. BDM inhibited I(NCX) in CCL39 cells
      expressing NCX1 and in its mutant in which its three major phosphorylatable
      serine residues were replaced with alanines. 9. We conclude that BDM inhibits
      I(NCX) but the mechanism of inhibition is not by dephosphorylation of the
      Na(+)/Ca(2+) exchanger as a 'chemical phosphatase'.

PMID- 11250886
TI  - Vascular endothelial growth factor and the in vivo increase in plasma
      extravasation in the hamster cheek pouch.
AB  - 1. The purpose of this study in the hamster cheek pouch was to determine whether
      or not vascular endothelial growth factor (VEGF) induced changes in plasma
      extravasation and if so, the mechanism(s) involved. 2. The cheek pouch
      microcirculatory bed of the anaesthetized hamster was directly observed under
      microscope and the number of vascular leakage sites, as shown by fluorescein
      isothiocyanate (FITC-dextran, 150 kD) extravasation, was counted. Drugs and VEGF
      were applied topically. VEGF from 0.05 to 0.5 microg ml(-1) (1.2 to 12 nM)
      produced a dose-dependent increase in the number of microvascular leakage sites
      from virtually none in basal conditions to up to 250 in some pouches. The effects
      of VEGF (0.1 microg ml(-1) or 2.4 nM) were blocked in a concentration-dependent
      manner by the non-specific heparin growth factor antagonist TBC-1635 (0.1, 1 and
      3microM). The placenta growth factor (PlGF-1: 0.1 and 0.5 microg ml(-1) or 3.4
      and 17 nM) did not increase plasma extravasation, per se, but abolished the
      effects of VEGF (2.4 nM). 3. The increases in microvascular leakage produced by
      VEGF (2.4 nM) were partially but significantly (P<0.05) inhibited by genistein (5
      and 10 microM, up to 33% inhibition), LY 294002 (30 microM, 41%),
      bisindolylmaleimide (1 microM, 65%) and virtually abolished by indomethacin (3
      microM, 88%) and L-nitro-arginine (10 microM, 95%), these drugs being inhibitors
      of tyrosine kinase, phosphatidylinositol-3-kinase, protein kinase C, cyclo
      oxygenase and nitric oxide synthase respectively. None of these inhibitors, at
      the concentration tested, induced alone an increase in plasma extravasation. 4.
      These results indicate that the VEGF-induced plasma extravasation may involve the
      stimulation of VEGF-R2 (Flk-1/KDR) and the activation of phosphatidylinositol-3
      kinase and protein kinase C. The production of both nitric oxide and
      prostaglandin is required to observe an increase in vascular leakage.

PMID- 11250887
TI  - Glucocorticoids inhibit lipopolysaccharide-induced up-regulation of arginase in
      rat alveolar macrophages.
AB  - 1. As arginase by limiting nitric oxide (NO) synthesis may play a role in airway
      hyperresponsiveness and glucocorticoids are known to induce the expression of
      arginase I in hepatic cells, glucocorticoid effects on arginase in alveolar
      macrophages (AM Phi) were studied. 2. Rat AM Phi were cultured in absence or
      presence of test substances. Thereafter, nitrite accumulation, arginase activity,
      and the expression pattern of inducible NO synthase, arginase I and II mRNA (RT -
      PCR) and proteins (immunoblotting) were determined. 3. Lipopolyssacharides (LPS,
      20 h) caused an about 2 fold increase in arginase activity, whereas interferon
      gamma (IFN-gamma), like LPS a strong inducer of NO synthesis, had no effect. 4.
      Dexamethasone decreased arginase activity by about 25% and prevented the LPS
      induced increase. Mifepristone (RU-486) as partial glucocorticoid receptor
      agonist inhibited LPS-induced increase by 45% and antagonized the inhibitory
      effect of dexamethasone. 5. Two different inhibitors of the NF-kappa B-pathway
      also prevented LPS-induced increase in arginase activity. 6. Rat AM Phi expressed
      mRNA and protein of arginase I and II, but arginase I expression was stronger.
      Arginase I mRNA and protein was not affected by IFN-gamma, but increased by LPS
      and this effect was prevented by dexamethasone. Both, LPS and IFN-gamma enhanced
      the levels of arginase II mRNA and protein, effects also inhibited by
      dexamethasone. As IFN-gamma did not affect total arginase activity, arginase II
      may represent only a minor fraction of total arginase activity. 7. In rat AM Phi
      glucocorticoids inhibit LPS-induced up-regulation of arginase activity, an effect
      which may contribute to the beneficial effects of glucocorticoids in the
      treatment of inflammatory airway diseases.

PMID- 11250888
TI  - Multiple classes of stem cells in cutaneous epithelium: a lineage analysis of
      adult mouse skin.
AB  - Continuous renewal of the epidermis and its appendages throughout life depends on
      the proliferation of a distinct population of cells called stem cells. We have
      used in situ retrovirus-mediated gene transfer to genetically mark cutaneous
      epithelial stem cells of adolescent mice, and have followed the fate of the
      marked progeny after at least 37 epidermal turnovers and five cycles of
      depilation-induced hair growth. Histological examination of serial sections of
      labeled pilosebaceous units demonstrated a complex cell lineage. In most
      instances, labeled cells were confined to one or more follicular compartments or
      solely to sebaceous glands. Labeled keratinocytes in interfollicular epidermis
      were confined to distinct columnar units representing epidermal proliferative
      units. The contribution of hair follicles to the epidermis was limited to a small
      rim of epidermis at the margin of the follicle, indicating that long term
      maintenance of interfollicular epidermis was independent of follicle-derived
      cells. Our results indicate the presence of multiple stem cells in cutaneous
      epithelium, some with restricted lineages in the absence of major injury.

PMID- 11250889
TI  - Signalling via vascular endothelial growth factor receptor-3 is sufficient for
      lymphangiogenesis in transgenic mice.
AB  - Vascular endothelial growth factor receptor-3 (VEGFR-3) has an essential role in
      the development of embryonic blood vessels; however, after midgestation its
      expression becomes restricted mainly to the developing lymphatic vessels. The
      VEGFR-3 ligand VEGF-C stimulates lymphangiogenesis in transgenic mice and in
      chick chorioallantoic membrane. As VEGF-C also binds VEGFR-2, which is expressed
      in lymphatic endothelia, it is not clear which receptors are responsible for the
      lymphangiogenic effects of VEGF-C. VEGF-D, which binds to the same receptors, has
      been reported to induce angiogenesis, but its lymphangiogenic potential is not
      known. In order to define the lymphangiogenic signalling pathway we have created
      transgenic mice overexpressing a VEGFR-3-specific mutant of VEGF-C (VEGF-C156S)
      or VEGF-D in epidermal keratinocytes under the keratin 14 promoter. Both
      transgenes induced the growth of lymphatic vessels in the skin, whereas the blood
      vessel architecture was not affected. Evidence was also obtained that these
      growth factors act in a paracrine manner in vivo. These results demonstrate that
      stimulation of the VEGFR-3 signal transduction pathway is sufficient to induce
      specifically lymphangiogenesis in vivo.

PMID- 11250890
TI  - A novel function for the Tec family tyrosine kinase Itk in activation of beta 1
      integrins by the T-cell receptor.
AB  - Stimulation of T cells via the CD3--T-cell receptor (TCR) complex results in
      rapid increases in beta 1 integrin-mediated adhesion via poorly defined
      intracellular signaling events. We demonstrate that TCR-mediated activation of
      beta 1 integrins requires activation of the Tec family tyrosine kinase Itk and
      phosphatidylinositol 3-kinase (PI 3-K)-dependent recruitment of Itk to detergent
      insoluble glycosphingolipid-enriched microdomains (DIGs) via binding of the
      pleckstrin homology domain of Itk to the PI 3-K product PI(3,4,5)-P(3).
      Activation of PI 3-K and the src family kinase Lck, via stimulation of the CD4 co
      receptor, can initiate beta 1 integrin activation that is dependent on Itk
      function. Targeting of Itk specifically to DIGs, coupled with CD4 stimulation,
      can also activate beta 1 integrin function independently of TCR stimulation.
      Changes in beta 1 integrin function mediated by TCR activation of Itk are also
      accompanied by Itk-dependent modulation of the actin cytoskeleton. Thus, TCR
      mediated activation of beta 1 integrins involves membrane relocalization and
      activation of Itk via coordinate action of PI 3-K and a src family tyrosine
      kinase.

PMID- 11250891
TI  - Enteropathogenic Escherichia coli mediates antiphagocytosis through the
      inhibition of PI 3-kinase-dependent pathways.
AB  - The extracellular pathogen enteropathogenic Escherichia coli (EPEC) uses a type
      III secretion system to inhibit its uptake by macrophages. We show that EPEC
      antiphagocytosis is independent of the translocated intimin receptor Tir and
      occurs by preventing F-actin polymerization required for bacterial uptake. EPEC
      macrophage contact triggered activation of phosphatidylinositol (PI) 3-kinase,
      which was subsequently inhibited in a type III secretion-dependent manner.
      Inhibition of PI 3-kinase significantly reduced uptake of a secretion-deficient
      mutant, without affecting antiphagocytosis by the wild type, suggesting that EPEC
      blocks a PI 3-kinase-dependent phagocytic pathway. EPEC specifically inhibited Fc
      gamma receptor- but not CR3-receptor mediated phagocytosis of opsonized zymosan.
      We showed that EPEC inhibits PI 3-kinase activity rather than its recruitment to
      the site of bacterial contact. Phagocytosis of a secretion mutant correlated with
      the association of PI 3-kinase with tyrosine-phosphorylated proteins, which wild
      type EPEC prevented. These results show that EPEC blocks its uptake by inhibiting
      a PI 3-kinase-mediated pathway, and translocates effectors other than Tir to
      interfere with actin-driven host cell processes. This constitutes a novel
      mechanism of phagocytosis avoidance by an extracellular pathogen.

PMID- 11250892
TI  - The role of Plo1 kinase in mitotic commitment and septation in
      Schizosaccharomyces pombe.
AB  - Plo1-associated casein kinase activity peaked during mitosis before septation.
      Phosphatase treatment abolished this activity. Mitotic Plo1 activation had a
      requirement for prior activation of M-phase promoting factor (MPF), suggesting
      that Plo1 does not act as a mitotic trigger kinase to initiate MPF activation
      during mitotic commitment. A link between Plo1 and the septum initiating network
      (SIN) has been suggested by the inability of plo1 Delta cells to septate and the
      prolific septation following plo1(+) overexpression. Interphase activation of
      Spg1, the G protein that modulates SIN activity, induced septation but did not
      stimulate Plo1-associated kinase activity. Conversely, SIN inactivation did not
      affect the mitotic stimulation of Plo1-associated kinase activity. plo1.ts4 cells
      formed a misshapen actin ring, but rarely septated at 36 degrees C. Forced
      activation of Spg1 enabled plo1.ts4 mutant cells, but not cells with defects in
      the SIN component Sid2, to convert the actin ring to a septum. The ability of
      plo1(+) overexpression to induce septation was severely compromised by SIN
      inactivation. We propose that Plo1 acts before the SIN to control septation.

PMID- 11250893
TI  - Segregation of TRAF6-mediated signaling pathways clarifies its role in
      osteoclastogenesis.
AB  - Signals emanating from the receptor for interleukin-1 (IL-1), lipopolysaccharide
      (LPS) or osteoclast differentiation factor/receptor activator of NF kappa B
      ligand (ODF/RANKL) stimulate transcription factors AP-1 through mitogen-activated
      protein kinase (MAPK) activation and NF kappa B through I kappa B kinase (IKK)
      activation. These kinases are thought to be activated by tumor necrosis factor
      receptor-associated factor 6 (TRAF6). However, molecular mechanisms by which
      TRAF6 activates various downstream kinases remain to be elucidated. We identified
      functional domains of TRAF6 under physiological conditions established by
      appropriate expression of TRAF6 mutants in TRAF6-deficient cells. In IL-1 and LPS
      signaling pathways, the RING finger and first zinc finger domains are not
      required for NF kappa B activation but are required for full activation of MAPK.
      However, IL-1 and LPS signals utilize distinct regions within the zinc finger
      domains of TRAF6 to activate NF kappa B. Furthermore, the RING finger domain is
      not required for differentiation of splenocytes to multinuclear osteoclasts, but
      is essential for osteoclast maturation. Thus, TRAF6 plays essential roles in both
      the differentiation and maturation of osteoclasts by activating various kinases
      via its multiple domains.

PMID- 11250894
TI  - Oxa1p acts as a general membrane insertion machinery for proteins encoded by
      mitochondrial DNA.
AB  - Oxa1p is a member of the conserved Oxa1/YidC/Alb3 protein family involved in the
      membrane insertion of proteins. Oxa1p has been shown previously to directly
      facilitate the export of the N-terminal domains of membrane proteins across the
      inner membrane to the intermembrane space of mitochondria. Here we report on a
      general role of Oxa1p in the membrane insertion of proteins. (i) The function of
      Oxa1p is not limited to the insertion of membrane proteins that undergo N
      terminal tail export; rather, it also extends to the insertion of other polytopic
      proteins such as the mitochondrially encoded Cox1p and Cox3p proteins. These are
      proteins whose N-termini are retained in the mitochondrial matrix. (ii) Oxa1p
      interacts directly with these substrates prior to completion of their synthesis.
      (iii) The interaction of Oxa1p with its substrates is particularly strong when
      nascent polypeptide chains are inserted into the inner membrane, suggesting a
      direct function of Oxa1p in co-translational insertion from the matrix. Taken
      together, we conclude that the Oxa1 complex represents a general membrane protein
      insertion machinery in the inner membrane of mitochondria.

PMID- 11250895
TI  - Male germ cells and photoreceptors, both dependent on close cell-cell
      interactions, degenerate upon ClC-2 Cl(-) channel disruption.
AB  - The functions of some CLC Cl(-) channels are evident from human diseases that
      result from their mutations, but the role of the broadly expressed ClC-2 Cl(-)
      channel is less clear. Several important functions have been attributed to ClC-2,
      but contrary to these expectations ClC-2-deficient mice lacked overt
      abnormalities except for a severe degeneration of the retina and the testes,
      which led to selective male infertility. Seminiferous tubules did not develop
      lumina and germ cells failed to complete meiosis. Beginning around puberty there
      was a massive death of primary spermatocytes and later also of spermatogonia.
      Tubules were filled with abnormal Sertoli cells, which normally express ClC-2 in
      patches adjacent to germ cells. In the retina, photoreceptors lacked normal outer
      segments and degenerated between days P10 and P30. The current across the retinal
      pigment epithelium was severely reduced at P36. Thus, ClC-2 disruption entails
      the death of two cell types which depend on supporting cells that form the blood
      testes and blood-retina barriers. We propose that ClC-2 is crucial for
      controlling the ionic environment of these cells.

PMID- 11250896
TI  - Cyclophilin A regulates HIV-1 infectivity, as demonstrated by gene targeting in
      human T cells.
AB  - The human immunodeficiency virus type 1 (HIV-1) Gag polyprotein binds most
      members of the cyclophilin family of peptidyl-prolyl isomerases. Of 15 known
      human cyclophilins, cyclophilin A (CypA) has been the focus of investigation
      because it was detected in HIV-1 virions. To determine whether CypA promotes HIV
      1 replication, we deleted the gene encoding CypA (PPIA) in human CD4(+) T cells
      by homologous recombination. HIV-1 replication in PPIA(-/-) cells was decreased
      and not inhibited further by cyclosporin or gag mutations that disrupt Gag's
      interaction with cyclophilins, indicating that no other cyclophilin family
      members promote HIV-1 replication. The defective replication phenotype was
      specific for wild-type HIV-1 since HIV-2/SIV isolates, as well as HIV-1 bearing a
      gag mutation that confers cyclosporin resistance, replicated the same in
      PPIA(+/+) and PPIA(-/-) cells. Stable re-expression of CypA in PPIA(-/-) cells
      restored HIV-1 replication to an extent that correlated with steady-state levels
      of CypA. Finally, virions from PPIA(-/-) cells possessed no obvious biochemical
      abnormalities but were less infectious than virions from wild-type cells. These
      data formally demonstrate that CypA regulates the infectivity of HIV-1 virions.

PMID- 11250897
TI  - Adenovirus-activated PKA and p38/MAPK pathways boost microtubule-mediated nuclear
      targeting of virus.
AB  - Nuclear targeting of adenovirus is mediated by the microtubule-dependent, minus
      end-directed motor complex dynein/dynactin, in competition with plus- end
      directed motility. We demonstrate that adenovirus transiently activates two
      distinct signaling pathways to enhance nuclear targeting. The first pathway
      activates integrins and cAMP-dependent protein kinase A (PKA). The second pathway
      activates the p38/MAP kinase and the downstream MAPKAP kinase 2 (MK2), dependent
      on the p38/MAPK kinase MKK6, but independent of integrins and PKA. Motility
      measurements in PKA-inhibited, p38-inhibited or MK2-lacking (MK2(-/-)) cells
      indicate that PKA and p38 stimulated both the frequency and velocity of minus-end
      directed viral motility without affecting the perinuclear localization of
      transferrin-containing endosomal vesicles. p38 also suppressed lateral viral
      motilities and MK2 boosted the frequency of minus-end-directed virus transport.
      Nuclear targeting of adenovirus was rescued in MK2(-/-) cells by overexpression
      of hsp27, an MK2 target that enhances actin metabolism. Our results demonstrate
      that complementary activities of PKA, p38 and MK2 tip the transport balance of
      adenovirus towards the nucleus and thus enhance infection.

PMID- 11250898
TI  - Kinetic analysis of translocation through nuclear pore complexes.
AB  - The mechanism of facilitated translocation through nuclear pore complexes (NPCs)
      is only poorly understood. Here, we present a kinetic analysis of the process
      using various model substrates. We find that the translocation capacity of NPCs
      is unexpectedly high, with a single NPC allowing a mass flow of nearly 100 MDa/s
      and rates in the order of 10(3) translocation events per second. Our data further
      indicate that high affinity interactions between the translocation substrate and
      NPC components are dispensable for translocation. We propose a 'selective phase
      model' that could explain how NPCs function as a permeability barrier for inert
      molecules and yet become selectively permeable for nuclear transport receptors
      and receptor-cargo complexes.

PMID- 11250899
TI  - p300/CBP-mediated p53 acetylation is commonly induced by p53-activating agents
      and inhibited by MDM2.
AB  - The tumor suppressor p53 is activated in response to many types of cellular and
      environmental insults via mechanisms involving post-translational modification.
      Here we demonstrate that, unlike phosphorylation, p53 invariably undergoes
      acetylation in cells exposed to a variety of stress-inducing agents including
      hypoxia, anti-metabolites, nuclear export inhibitor and actinomycin D treatment.
      In vivo, p53 acetylation is mediated by the p300 and CBP acetyltransferases.
      Overexpression of either p300 or CBP, but not an acetyltransferase-deficient
      mutant, efficiently induces specific p53 acetylation. In contrast, MDM2, a
      negative regulator of p53, actively suppresses p300/CBP-mediated p53 acetylation
      in vivo and in vitro. This inhibitory activity of MDM2 on p53 acetylation is in
      turn abrogated by tumor suppressor p19(ARF), indicating that regulation of
      acetylation is a central target of the p53-MDM2-p19(ARF) feedback loop.
      Functionally, inhibition of deacetylation promotes p53 stability, suggesting that
      acetylation plays a positive role in the accumulation of p53 protein in stress
      response. Our results provide evidence that p300/CBP-mediated acetylation may be
      a universal and critical modification for p53 function.

PMID- 11250900
TI  - A subfamily of RNA-binding DEAD-box proteins acts as an estrogen receptor alpha
      coactivator through the N-terminal activation domain (AF-1) with an RNA
      coactivator, SRA.
AB  - One class of the nuclear receptor AF-2 coactivator complexes contains the SRC
      1/TIF2 family, CBP/p300 and an RNA coactivator, SRA. We identified a subfamily of
      RNA-binding DEAD-box proteins (p72/p68) as a human estrogen receptor alpha (hER
      alpha) coactivator in the complex containing these factors. p72/p68 interacted
      with both the AD2 of any SRC-1/TIF2 family protein and the hER alpha A/B domain,
      but not with any other nuclear receptor tested. p72/p68, TIF2 (SRC-1) and SRA
      were co-immunoprecipitated with estrogen-bound hER alpha in MCF7 cells and in
      partially purified complexes associated with hER alpha from HeLa nuclear
      extracts. Estrogen induced co-localization of p72 with hER alpha and TIF2 in the
      nucleus. The presence of p72/p68 potentiated the estrogen-induced expression of
      the endogenous pS2 gene in MCF7 cells. In a transient expression assay, a
      combination of p72/p68 with SRA and one TIF2 brought an ultimate synergism to the
      estrogen-induced transactivation of hER alpha. These findings indicate that
      p72/p68 acts as an ER subtype-selective coactivator through ER alpha AF-1 by
      associating with the coactivator complex to bind its AF-2 through direct binding
      with SRA and the SRC-1/TIF2 family proteins.

PMID- 11250901
TI  - Acetylation of TAF(I)68, a subunit of TIF-IB/SL1, activates RNA polymerase I
      transcription.
AB  - Mammalian rRNA genes are preceded by a terminator element that is recognized by
      the transcription termination factor TTF-I. In exploring the functional
      significance of the promoter-proximal terminator, we found that TTF-I associates
      with the p300/CBP-associated factor PCAF, suggesting that TTF-I may target
      histone acetyltransferase to the rDNA promoter. We demonstrate that PCAF
      acetylates TAF(I)68, the second largest subunit of the TATA box-binding protein
      (TBP)-containing factor TIF-IB/SL1, and acetylation enhances binding of TAF(I)68
      to the rDNA promoter. Moreover, PCAF stimulates RNA polymerase I (Pol I)
      transcription in a reconstituted in vitro system. Consistent with acetylation of
      TIF-IB/SL1 being required for rDNA transcription, the NAD(+)-dependent histone
      deacetylase mSir2a deacetylates TAF(I)68 and represses Pol I transcription. The
      results demonstrate that acetylation of the basal Pol I transcription machinery
      has functional consequences and suggest that reversible acetylation of TIF-IB/SL1
      may be an effective means to regulate rDNA transcription in response to external
      signals.

PMID- 11250902
TI  - The TRA-1 transcription factor binds TRA-2 to regulate sexual fates in
      Caenorhabditis elegans.
AB  - The tra-1 and tra-2 sex-determining genes promote female fates in Caenorhabditis
      elegans. Classical genetic studies placed tra-1 as the terminal regulator of the
      pathway with tra-2 acting upstream as a regulator of regulators of tra-1. Here we
      report the surprising result that the TRA-1 transcription factor binds the
      intracellular domain of the TRA-2 membrane protein. This binding is dependent on
      the MX regulatory domain, a region of the TRA-2 intracellular domain shown
      previously to be critical for the onset of hermaphrodite spermatogenesis. The
      functional importance of the TRA-1-TRA-2 physical interaction is supported by
      genetic interactions between tra-1(0) and tra-2(mx) mutations: a reduction of tra
      1 gene dose from two copies to one copy enhances the tra-2(mx) feminization
      phenotype, but has no apparent somatic effect. In Caenorhabditis briggsae, we
      also find an MX-dependent interaction between Cb-TRA-1 and Cb-TRA-2, but
      intriguingly, no cross-species interactions are seen. The conservation of the TRA
      1- TRA-2 interaction underscores its importance in sex determination.

PMID- 11250903
TI  - hRRN3 is essential in the SL1-mediated recruitment of RNA Polymerase I to rRNA
      gene promoters.
AB  - A crucial step in transcription is the recruitment of RNA polymerase to
      promoters. In the transcription of human rRNA genes by RNA Polymerase I (Pol I),
      transcription factor SL1 has a role as the essential core promoter binding
      factor. Little is known about the mechanism by which Pol I is recruited. We
      provide evidence for an essential role for hRRN3, the human homologue of a yeast
      Pol I transcription factor, in this process. We find that whereas the bulk of
      human Pol I complexes (I alpha) are transcriptionally inactive, hRRN3 defines a
      distinct subpopulation of Pol I complexes (I beta) that supports specific
      initiation of transcription. Human RRN3 interacts directly with TAF(I)110 and
      TAF(I)63 of promoter-selectivity factor SL1. Blocking this connection prevents
      recruitment of Pol I beta to the rDNA promoter. Furthermore, hRRN3 can be found
      in transcriptionally autonomous Pol I holoenzyme complexes. We conclude that
      hRRN3 functions to recruit initiation-competent Pol I to rRNA gene promoters. The
      essential role for hRRN3 in linking Pol I to SL1 suggests a mechanism for growth
      control of Pol I transcription.

PMID- 11250904
TI  - N-myc enhances the expression of a large set of genes functioning in ribosome
      biogenesis and protein synthesis.
AB  - The myc oncogenes are frequently activated in human tumors, but there is no
      comprehensive insight into the target genes and downstream cellular pathways of
      these transcription factors. We applied serial analysis of gene expression (SAGE)
      to identify targets of N-myc in neuroblastomas. Analysis of 42,000 mRNA
      transcript tags in SAGE libraries of N-myc- transfected and control neuroblastoma
      cells revealed 114 up-regulated genes. The majority of these genes have a role in
      ribosome assembly and activity. Northern blot analysis confirmed up-regulation of
      all tested transcripts. Induction was complete within 4 h after N-myc expression.
      The large majority of the ribosomal proteins were induced, as well as genes
      controlling rRNA maturation. Cellular rRNA content was 45% induced. SAGE
      libraries and northern blot analysis confirmed up-regulation of many of these
      genes in N-myc-amplified neuroblastomas. As N-myc can functionally replace c-myc,
      we analyzed whether N-myc targets were induced by c-myc as well. Approximately
      40% of these N-myc targets were up-regulated in a c-myc-transfected melanoma cell
      line. These data suggest that myc genes function as major regulators of the
      protein synthesis machinery.

PMID- 11250905
TI  - Annealing of RNA editing substrates facilitated by guide RNA-binding protein
      gBP21.
AB  - RNA editing within the mitochondria of African trypanosomes is characterized by
      the insertion and deletion of uridylate residues into otherwise incomplete
      primary transcripts. The reaction takes place in a high molecular mass
      ribonucleoprotein (RNP) complex of uncertain composition. Furthermore, factors
      that interact with the RNP complex during the reaction are by and large unknown.
      Here we present evidence for an editing-related biochemical activity of the gRNA
      binding protein gBP21. Using recombinant gBP21 preparations, we show that the
      protein stimulates the annealing of gRNAs to cognate pre-mRNAs in vitro. This
      represents the presumed first step of the editing reaction. Kinetic data
      establish an enhancement of the second order rate constant for the gRNA- pre-mRNA
      interaction. gBP21-mediated annealing is not exclusive for RNA editing substrates
      since complementary RNAs, unrelated to the editing process, can also be
      hybridized. The gBP21-dependent RNA annealing activity was identified in
      mitochondrial extracts of trypanosomes and can be inhibited by
      immunoprecipitation of the polypeptide. The data suggest a factor-like
      contribution of gBP21 to the RNA editing process by accelerating the rate of gRNA
      pre-mRNA anchor formation.

PMID- 11250906
TI  - Non-templated addition of nucleotides to the 3' end of nascent RNA during RNA
      editing in Physarum.
AB  - RNAs in Physarum: mitochondria contain extra nucleotides that are not encoded by
      the mitochondrial genome, at least in the traditional sense. While it is known
      that insertion of non-encoded nucleotides is linked to RNA synthesis, the exact
      nature of this relationship remains unclear. Here we demonstrate that the
      efficiency of editing is sensitive not only to the concentration of the
      nucleotide that is inserted, but also to the concentration of the nucleotide
      templated just downstream of an editing site. These data strongly support a co
      transcriptional mechanism of Physarum: RNA editing in which non-encoded
      nucleotides are added to the 3' end of nascent RNAs. These results also suggest
      that transcription elongation and nucleotide insertion are competing processes
      and that recognition of editing sites most likely involves transient pausing by
      the Physarum: mitochondrial RNA polymerase. In addition, the pattern of
      nucleotide concentration effects, the context of editing sites and the accuracy
      of the mitochondrial RNA polymerase argue that the mechanism of Physarum: editing
      is distinct from that of other co-transcriptional editing systems.

PMID- 11250907
TI  - Structure, folding and activity of the VS ribozyme: importance of the 2-3-6
      helical junction.
AB  - The VS nucleolytic ribozyme has a core comprising five helices organized by two
      three-way junctions. The ribozyme can act in trans on a hairpin-loop substrate,
      with which it interacts via tertiary contacts. We have determined that one of the
      junctions (2-3-6) undergoes two-stage ion-dependent folding into a stable
      conformation, and have determined the global structure of the folded junction
      using long-range distance restraints derived from fluorescence resonance energy
      transfer. A number of sequence variants in the junction are severely impaired in
      ribozyme cleavage, and there is good correlation between changes in activity and
      alteration in the folding of junction 2-3-6. These studies point to a special
      importance of G and A nucleotides immediately adjacent to helix II, and
      comparison with a similar junction of known structure indicates that this could
      adopt a guanine-wedge structure. We propose that the 2-3-6 junction organizes
      important aspects of the structure of the ribozyme to facilitate productive
      association with the substrate, and suggest that this results in an interaction
      between the substrate and the A730 loop to create the active complex.

PMID- 11250908
TI  - The tRNA-binding moiety in GCN2 contains a dimerization domain that interacts
      with the kinase domain and is required for tRNA binding and kinase activation.
AB  - GCN2 stimulates translation of GCN4 mRNA in amino acid-starved cells by
      phosphorylating translation initiation factor 2. GCN2 is activated by binding of
      uncharged tRNA to a domain related to histidyl-tRNA synthetase (HisRS). The HisRS
      like region contains two dimerization domains (HisRS-N and HisRS-C) required for
      GCN2 function in vivo but dispensable for dimerization by full-length GCN2.
      Residues corresponding to amino acids at the dimer interface of Escherichia coli
      HisRS were required for dimerization of recombinant HisRS-N and for tRNA binding
      by full-length GCN2, suggesting that HisRS-N dimerization promotes tRNA binding
      and kinase activation. HisRS-N also interacted with the protein kinase (PK)
      domain, and a deletion impairing this interaction destroyed GCN2 function without
      reducing tRNA binding; thus, HisRS-N-PK interaction appears to stimulate PK
      function. The C-terminal domain of GCN2 (C-term) interacted with the PK domain in
      a manner disrupted by an activating PK mutation (E803V). These results suggest
      that the C-term is an autoinhibitory domain, counteracted by tRNA binding. We
      conclude that multiple domain interactions, positive and negative, mediate the
      activation of GCN2 by uncharged tRNA.

PMID- 11250909
TI  - 5' cloverleaf in poliovirus RNA is a cis-acting replication element required for
      negative-strand synthesis.
AB  - A cloverleaf structure at the 5' terminus of poliovirus RNA binds viral and
      cellular proteins. To examine the role of the cloverleaf in poliovirus
      replication, we determined how cloverleaf mutations affected the stability,
      translation and replication of poliovirus RNA in HeLa S10 translation-replication
      reactions. Mutations within the cloverleaf destabilized viral RNA in these
      reactions. Adding a 5' 7-methyl guanosine cap fully restored the stability of the
      mutant RNAs and had no effect on their translation. These results indicate that
      the 5' cloverleaf normally protects uncapped poliovirus RNA from rapid
      degradation by cellular nucleases. Preinitiation RNA replication complexes formed
      with the capped mutant RNAs were used to measure negative-strand synthesis.
      Although the mutant RNAs were stable and functional mRNAs, they were not active
      templates for negative-strand RNA synthesis. Therefore, the 5' cloverleaf is a
      multifunctional cis-acting replication element required for the initiation of
      negative-strand RNA synthesis. We propose a replication model in which the 5' and
      3' ends of viral RNA interact to form a circular ribonucleoprotein complex that
      regulates the stability, translation and replication of poliovirus RNA.

PMID- 11250911
TI  - The DnaB.DnaC complex: a structure based on dimers assembled around an occluded
      channel.
AB  - Replicative helicases are motor proteins that unwind DNA at replication forks.
      Escherichia coli DnaB is the best characterized member of this family of enzymes.
      We present the 26 A resolution three-dimensional structure of the DnaB hexamer in
      complex with its loading partner, DnaC, obtained from cryo-electron microscopy.
      Analysis of the volume brings insight into the elaborate way the two proteins
      interact, and provides a structural basis for control of the symmetry state and
      inactivation of the helicase by DnaC. The complex is arranged on the basis of
      interactions among DnaC and DnaB dimers. DnaC monomers are observed for the first
      time to arrange as three dumb-bell-shaped dimers that interlock into one of the
      faces of the helicase. This could be responsible for the freezing of DnaB in a
      C(3) architecture by its loading partner. The central channel of the helicase is
      almost occluded near the end opposite to DnaC, such that even single-stranded DNA
      could not pass through. We propose that the DnaB N-terminal domain is located at
      this face.

PMID- 11250910
TI  - Crystal structure of HIV-1 reverse transcriptase in complex with a polypurine
      tract RNA:DNA.
AB  - We have determined the 3.0 A resolution structure of wild-type HIV-1 reverse
      transcriptase in complex with an RNA:DNA oligonucleotide whose sequence includes
      a purine-rich segment from the HIV-1 genome called the polypurine tract (PPT).
      The PPT is resistant to ribonuclease H (RNase H) cleavage and is used as a primer
      for second DNA strand synthesis. The 'RNase H primer grip', consisting of amino
      acids that interact with the DNA primer strand, may contribute to RNase H
      catalysis and cleavage specificity. Cleavage specificity is also controlled by
      the width of the minor groove and the trajectory of the RNA:DNA, both of which
      are sequence dependent. An unusual 'unzipping' of 7 bp occurs in the adenine
      stretch of the PPT: an unpaired base on the template strand takes the base
      pairing out of register and then, following two offset base pairs, an unpaired
      base on the primer strand re-establishes the normal register. The structural
      aberration extends to the RNase H active site and may play a role in the
      resistance of PPT to RNase H cleavage.

PMID- 11250912
TI  - Mechanism of origin unwinding: sequential binding of DnaA to double- and single
      stranded DNA.
AB  - The initiator protein DnaA of Escherichia coli binds to a 9mer consensus
      sequence, the DnaA box (5'-TT(A/T)TNCACA). If complexed with ATP it adopts a new
      binding specificity for a 6mer consensus sequence, the ATP-DnaA box (5'-AGatct).
      Using DNase footprinting and surface plasmon resonance we show that binding to
      ATP-DnaA boxes in the AT-rich region of oriC of E.coli requires binding to the
      9mer DnaA box R1. Cooperative binding of ATP-DnaA to the AT-rich region results
      in its unwinding. ATP-DnaA subsequently binds to the single-stranded region,
      thereby stabilizing it. This demonstrates an additional binding specificity of
      DnaA protein to single-stranded ATP-DnaA boxes. Binding affinities, as judged by
      the DnaA concentrations required for site protection in footprinting, were
      approximately 1 nM for DnaA box R1, 400 nM for double-stranded ATP-DnaA boxes and
      40 nM for single-stranded ATP-DnaA boxes, respectively. We propose that
      sequential recognition of high- and low-affinity sites, and binding to single
      stranded origin DNA may be general properties of initiator proteins in initiation
      complexes.

PMID- 11250913
TI  - Human DNA polymerase beta initiates DNA synthesis during long-patch repair of
      reduced AP sites in DNA.
AB  - Simple base damages are repaired through a short-patch base excision pathway
      where a single damaged nucleotide is removed and replaced. DNA polymerase beta
      (Pol beta) is responsible for the repair synthesis in this pathway and also
      removes a 5'-sugar phosphate residue by catalyzing a beta-elimination reaction.
      How ever, some DNA lesions that render deoxyribose resistant to beta-elimination
      are removed through a long-patch repair pathway that involves strand displacement
      synthesis and removal of the generated flap by specific endonuclease. Three human
      DNA polymerases (Pol beta, Pol delta and Pol epsilon) have been proposed to play
      a role in this pathway, however the identity of the polymerase involved and the
      polymerase selection mechanism are not clear. In repair reactions catalyzed by
      cell extracts we have used a substrate containing a reduced apurinic/apyrimidinic
      (AP) site resistant to beta-elimination and inhibitors that selectively affect
      different DNA polymerases. Using this approach we find that in human cell
      extracts Pol beta is the major DNA polymerase incorporating the first nucleotide
      during repair of reduced AP sites, thus initiating long-patch base excision
      repair synthesis.

PMID- 11250914
TI  - Minireview: 11beta-hydroxysteroid dehydrogenase type 1- a tissue-specific
      amplifier of glucocorticoid action.
AB  - 11beta-hydroxysteroid dehydrogenases (11beta-HSDs) catalyze the interconversion
      of active glucocorticoids (cortisol, corticosterone) and inert 11-keto forms
      (cortisone, 11-dehydrocorticosterone). 11beta-HSD type 2 has a well recognized
      function as a potent dehydrogenase that rapidly inactivates glucocorticoids, thus
      allowing aldosterone selective access to otherwise nonselective mineralocorticoid
      receptors in the distal nephron. In contrast, the function of 11beta-HSD type 1
      has, until recently, been little understood. 11beta-HSD1 is an ostensibly
      reversible oxidoreductase in vitro, which is expressed in liver, adipose tissue,
      brain, lung, and other glucocorticoid target tissues. However, increasing data
      suggest that 11beta-HSD1 acts as a predominant 11beta-reductase in many intact
      cells, whole organs, and in vivo. This reaction direction locally regenerates
      active glucocorticoids within expressing cells, exploiting the substantial
      circulating levels of inert 11-keto steroids. While the biochemical determinants
      of the reaction direction are not fully understood, insights to its biological
      importance have been afforded by use of inhibitors in vivo, including in humans,
      and the generation of knockout mice. Such studies suggest 11beta-HSD1 effectively
      amplifies glucocorticoid action at least in the liver, adipose tissue, and the
      brain. Inhibition of 11beta-HSD1 represents a potential target for therapy of
      disorders that might be ameliorated by local reduction of glucocorticoid action,
      including type 2 diabetes, obesity, and age-related cognitive dysfunction.

PMID- 11250915
TI  - Editorial: the oxytocin/oxytocin receptor system-expect the unexpected.

PMID- 11250916
TI  - Transcriptional regulation of oxytocin receptor by interleukin-1beta and
      interleukin-6.
AB  - The up-regulation of oxytocin (OT) receptors in late pregnancy results
      principally from increased synthesis of messenger RNA. The 5'-flanking region of
      the human OT receptor gene contains several putative binding sites for nuclear
      factor-interleukin-6 (NF-IL6), also known as CAAT/enhancer binding protein-beta.
      This trans-acting factor modulates the expression of genes involved in acute
      inflammatory responses. Proinflammatory cytokines, such as IL-1beta or IL-6, have
      been implicated as mediators in both preterm and term labor, particularly in
      association with intrauterine infection. We hypothesized that IL-1beta and IL-6
      induce OT receptor gene expression in human myometrial cells, and this is
      mediated by NF-IL6 and cognate response elements in the 5'-flanking region of the
      OT receptor gene. Contrary to the hypothesis, both IL-1beta and IL-6 treatment
      resulted in a significant decrease in OT receptor messenger RNA measured by
      ribonuclease protection analysis. Using electrophoretic mobility shift assay, we
      have shown that NF-IL6 is present at low levels that appear to be increased after
      treatment with either IL-1beta or IL-6. Using deletion analysis and functional
      transfection studies in HeLa cells, we demonstrated that the OT receptor gene
      promoter displays constitutive basal activity and is negatively regulated by both
      IL-1beta and IL-6. This suppressive ability of IL-1beta and IL-6 depends on the 
      1203/-722 region of the OT receptor promoter, which contains binding sites for NF
      IL6, acute phase response element, and NF-kappaB. Our findings suggest a role for
      IL-1beta and IL-6 in the transcriptional regulation of the human OT receptor
      gene.

PMID- 11250917
TI  - Synthetic carboxyl-terminal fragments of parathyroid hormone (PTH) decrease
      ionized calcium concentration in rats by acting on a receptor different from the
      PTH/PTH-related peptide receptor.
AB  - Even if the carboxyl-terminal (C-) fragments/intact (I-) PTH ratio is tightly
      regulated by the ionized calcium (Ca(2+)) concentration in humans and animals, in
      health and in disease, the physiological roles of C-PTH fragments and of the C
      PTH receptor remain elusive. To explore these issues, we studied the influence of
      synthetic C-PTH peptides of various lengths on Ca(2+) concentration and on the
      calcemic response to human (h) PTH-(1-34) and hPTH-(1-84) in anesthetized
      thyroparathyroidectomized (TPTX) rats. We also looked at the capacity of these
      PTH preparations to react with the PTH/PTHrP receptor and with a receptor for the
      carboxyl (C)-terminal portion of PTH (C-PTH receptor) in rat osteosarcoma cells,
      ROS 17/2.8. The Ca(2+) concentration was reduced by 0.19 +/- 0.03 mmol/liter over
      2 h in all TPTX groups. Infusion of solvent over 2 more h had no further effect
      on the Ca(2+) concentration (-0.01 +/- 0.01 mmol/liter), whereas infusion of hPTH
      (7-84) or a fragment mixture [10% hPTH-(7-84) and 45% each of hPTH-(39-84) and
      hPTH-(53-84)] 10 nmol/h further decreased the Ca(2+) concentration by 0.18 +/-
      0.02 (P<0.001) and 0.07+/-0.04 mmol/liter (P< 0.001), respectively. Infusion of
      hPTH-(1-84) or hPTH-(1-34) (1 nmol/h) increased the Ca(2+) concentration by 0.16
      +/- 0.03 (P < 0.001) and 0.19 +/- 0.03 mmol/liter (P < 0.001), respectively.
      Adding hPTH-(7-84) (10 nmol/h) to these preparations prevented the calcemic
      response and maintained Ca(2+) concentrations equal to or below levels observed
      in TPTX animals infused with solvent alone. Adding the fragment mixture (10
      nmol/h) to hPTH-(1-84) did not prevent a normal calcemic response, but partially
      blocked the response to hPTH-(1-34), and more than 3 nmol/h hPTH-(7-84) prevented
      it. Both hPTH-(1-84) and hPTH-(1-34) stimulated cAMP production in ROS 17/2.8
      clonal cells, whereas hPTH-(7-84) was ineffective in this respect. Both hPTH-(1
      84) and hPTH-(1-34) displaced (125)I-[Nle(8,18),Tyr(34)]hPTH-(1-34) amide from
      the PTH/PTHrP receptor, whereas hPTH-(7-84) had no such influence. Both hPTH-(1
      84) and hPTH-(7-84) displaced (125)I-[Tyr(34)]hPTH-(19-84) from the C-PTH
      receptor, the former preparation being more potent on a molar basis, whereas hPTH
      (1-34) had no effect. These results suggest that C-PTH fragments, particularly
      hPTH-(7-84), can influence the Ca(2+) concentration negatively in vivo and limit
      in such a way the calcemic responses to hPTH-(1-84) and hPTH-(1-34) by
      interacting with a receptor different from the PTH/PTHrP receptor, possibly a C
      PTH receptor.

PMID- 11250918
TI  - Identification of specific inhibin A-binding proteins on mouse Leydig (TM3) and
      sertoli (TM4) cell lines.
AB  - The binding of human inhibin A to cell surface binding proteins of mouse Leydig
      (TM3) and Sertoli (TM4) cell lines was investigated. Scatchard analysis
      identified two classes of inhibin A-binding sites on TM3 (K(d(1)) = 85 pM and
      4,160 sites/cell; K(d(2)) = 520 pM and 12,500 sites/cell) and TM4 (K(d(1)) = 61
      pM and 2,620 sites/cell; K(d(2)) = 520 pM and 10,400 sites/cell) cells. Compared
      with inhibin A, inhibin B only partially competed [(125)I]inhibin A binding (6
      8%), whereas activin A competed weakly (<0.01%). Chemical cross-linking of
      [(125)I]inhibin A to both cell lines identified five [(125)I]inhibin A binding
      complexes with apparent molecular masses of 70, 95, 145, 155, and more than 200
      kDa. Inhibin A displacement of [(125)I]inhibin A from each of these cross-linked
      species (ED(50) = 60-110 pM) closely resembled displacement from intact TM3
      (ED(50) = 97 +/- 32 pM) and TM4 (ED(50) = 75 +/- 28 pM) cells, suggesting that
      all of these proteins are involved in the high affinity inhibin A binding
      complex. Immunoprecipitation of iodinated inhibin A complexed to TM3 and TM4
      cells with an antibody against human betaglycan identified protein complexes of
      more than 200, 145, and 95 kDa. It is concluded that the high affinity binding
      complex for inhibin A found in these cell lines consists of betaglycan and
      several proteins of unknown identity and may represent the putative inhibin
      receptor complex.

PMID- 11250919
TI  - Estradiol and incubation temperature modulate regulation of steroidogenic factor
      1 in the developing gonad of the red-eared slider turtle.
AB  - Red-eared slider turtles are genetically bipotential for sex determination, with
      incubation temperature of the egg determining gonadal sex. At higher incubation
      temperatures, females are produced, possibly due to increased biosynthesis of
      estrogen. Exogenous estrogen causes the formation of ovaries, and prevention of
      estrogen biosynthesis results in the development of testes. In mammals,
      steroidogenic factor 1 (SF-1) regulates most genes required for estrogen
      biosynthesis from cholesterol. In mammals as well as red-eared slider turtles, SF
      1 is differentially expressed in males and females during gonadogenesis. To
      examine a possible role for SF-1 in temperature-dependent sex determination, we
      assayed its expression in red-eared slider turtles after treatments that alter
      sex development during gonadogenesis of the wild-type organism. We examined
      gonadal SF-1 expression in embryos 1) incubating at three different temperatures,
      2) after treating eggs with estrogen at a male-producing temperature, and 3)
      after inhibition of estrogen biosynthesis at a female-producing temperature. Our
      findings suggest that both temperature and estrogen lie upstream of SF-1 in a sex
      determining regulatory hierarchy in red-eared slider turtles and that estrogen
      directly or indirectly modulates the regulation of SF-1 expression.

PMID- 11250920
TI  - Isolation and characterization of myostatin complementary deoxyribonucleic acid
      clones from two commercially important fish: Oreochromis mossambicus and Morone
      chrysops.
AB  - In mammals, skeletal muscle mass is negatively regulated by a muscle-derived
      growth/differentiating factor named myostatin (MSTN) that belongs to the
      transforming growth factor-beta superfamily. Although putative MSTN homologs have
      been identified from several vertebrates, nonmammalian orthologs remained poorly
      defined. Thus, we isolated and characterized MSTN complementary DNA clones from
      the skeletal muscle of the tilapia Oreochromis mossambicus and the white bass
      Morone chrysops. The nucleic and amino acid sequences from both fish species are
      highly homologous to the previously identified mammalian and avian orthologs, and
      both possess conserved cysteine residues and putative RXXR proteolytic processing
      sites that are common to all transforming growth factor-beta family members.
      Western blotting of conditioned medium from human embryonal kidney (HEK293) cells
      overexpressing a His-tagged tilapia MSTN indicates that the secreted fish protein
      is processed in a manner similar to mouse MSTN. However, in contrast to mice,
      MSTN expression in tilapia is not limited to skeletal muscle as it occurs in many
      tissues. Furthermore, the timing of MSTN expression in developing tilapia larvae
      coincides with myogenesis. These results suggest that the biological actions of
      MSTN in the tilapia and possibly in other fishes may not be limited to myocyte
      growth repression, but may additionally influence different cell types and organ
      systems.

PMID- 11250921
TI  - Determination of three isoforms of the receptor activator of nuclear factor
      kappaB ligand and their differential expression in bone and thymus.
AB  - The receptor activator of nuclear factor (NF)-kappaB ligand [RANKL; also known as
      tumor necrosis factor-related activation-induced cytokine, osteoprotegerin
      ligand, and osteoclast differentiation factor] is known to bind with the receptor
      activator of NF-kappaB (RANK) and act not only as a key factor for
      osteoclastogenesis but also as a regulator of lymphocyte development. In this
      study, we found two additional isoforms of RANKL. RANKL 2 has a shorter
      intracellular domain than the original RANKL (RANKL 1), and RANKL 3 lacks a
      transmembrane domain and was thought to act as a soluble form. In the bone marrow
      stromal cell line ST2 and preosteoblastic cell line MC3T3-E1, all three RANKL
      isoforms were detected, but the expression of RANKL 2 was preferentially
      suppressed by treatment with 1alpha,25-dihydroxyvitamin D(3) and dexamethasone.
      In young adult thymus, CD4(-)CD8(-) double-negative cells were positive for all
      three isoforms, CD4(+)CD8(+) double-positive cells were positive for RANKL 1 and
      RANKL 3 but negative for RANKL 2, and CD4(+)CD8(-) and CD4(-)CD8(+) single
      positive cells were positive for all three isoforms. Immunofluorescence analyses
      of NIH3T3 cells transfected with each RANKL isoform indicated that the three
      RANKL isoforms were translated, and RANKL 2 protein predominantly stayed in the
      endoplasmic reticulum and Golgi networks. These results indicate that there are
      three kinds of RANKL-RANK pathways. The presence of multiple RANKL-RANK pathways
      suggests a more complicated RANKL-RANK system for osteoclastogenesis or T cell
      differentiation than previously thought.

PMID- 11250922
TI  - Characterization of 5'-flanking region of rat somatostatin receptor sst2 gene:
      transcriptional regulatory elements and activation by Pitx1 and estrogen.
AB  - The sst2 somatostatin receptor mediates the inhibitory effects of somatostatin on
      secretive and proliferative processes. We previously showed that sst2 is one of
      the major subtypes expressed in the rat pituitary, and its messenger RNA level is
      up-regulated by chronic treatment with estrogen. To investigate the molecular
      mechanisms regulating sst2 gene expression, we cloned the upstream region (9.5
      kb) from the translation initiation codon of the rat sst2 gene. It contained a
      single intron (5.0 kb) at the 5'-untranslated region, lacked TATA and CCAAT
      boxes, and had multiple transcriptional start sites. Transient transfection
      analysis with deleted mutants of a luciferase reporter construct showed that the
      promoter activity was regulated negatively and positively in the distal and
      proximal promoter regions, respectively. The promoter activity of each construct
      was more efficient in GH(3) pituitary cells than in nonpituitary cells. The
      construct (-77/+172/luc) containing a cAMP response element (CRE; -54/-47)
      provided maximum promoter activity, but a further 5'-deleted construct
      dramatically reduced the activity. Competitive gel shift and supershift assays
      indicated that Sp2 and Sp3 were bound to an Sp1 site (-40/-31), and activating
      transcription factor-2 and c-Jun were bound to a CRE site. Both Sp1 and CRE sites
      were essential for the full promoter activity. Overexpression of the pituitary
      homeoprotein Pitx1 activated the promoter activity of the -4066/+172/luc
      construct, and mapping analysis indicated the existence of two Pitx1 response
      sites, including the CRE site. Estrogen also increased the promoter activity of 
      77/+172/luc in GH(3) cells or in HeLa cells overexpressing both the estrogen
      receptor and c-Jun. These studies demonstrated the nature of the rat sst2 gene
      and the functional importance of both Sp1 and CRE sites in regulating sst2 gene
      expression and suggest that the CRE site mediates, at least partly, the promoter
      activity activated by Pitx1 or estrogen.

PMID- 11250923
TI  - Testosterone effect on insulin content, messenger ribonucleic acid levels,
      promoter activity, and secretion in the rat.
AB  - Coexistence of hyperinsulinemia and hyperandrogenism in women has been frequently
      described. Most of the studies addressing this issue have focused on the
      mechanisms by which insulin produces hyperandrogenism. In the present study, we
      analyzed the effects of testosterone in vivo and in vitro upon insulin gene
      expression and release in the rat. Our studies demonstrate that testosterone
      increases insulin messenger RNA (mRNA) levels in vitro as well as in vivo. In
      both prepuberal and intact adult rats, serum testosterone concentrations were
      positively correlated with insulin mRNA levels and insulin concentration in
      serum. Testosterone deprivation after gonadectomy decreased both insulin gene
      expression and serum insulin concentration. Insulin mRNA levels were partially
      restored after 3 days of testosterone administration and serum insulin was 80%
      and 27% above baseline values at 5 and 7 days posttreatment. Primary cultured
      pancreatic islets treated with the sexual steroid increased about 80% insulin
      mRNA, as well as protein, and release. In transfected islets, testosterone
      increased the activity of the -410 bp rat insulin promoter I by 154%. These data
      demonstrate that testosterone has a direct effect upon pancreatic islet function
      by favoring insulin gene expression and release.

PMID- 11250924
TI  - Cyclic adenosine 3',5'-monophosphate increases pancreatic glucokinase activity
      and gene expression.
AB  - Comparison of the pancreatic and hepatic glucokinase gene transcripts reveals
      tissue-specific control of expression and the existence of two distinct promoters
      in a single glucokinase gene. The existence of alternate promoters suggests that
      separate factors regulate glucokinase transcription in the two tissues. Hepatic
      glucokinase expression has been shown to be repressed by cAMP; however, in the
      pancreatic beta-cell it is unlikely that cAMP represses glucokinase activity, as
      cAMP is known to positively affect glucose-induced insulin secretion, a process
      that in mature islets requires pancreatic glucokinase activity. In this work we
      demonstrate that cAMP indeed has a stimulatory effect on pancreatic glucokinase.
      The cyclic nucleotide stimulates pancreatic glucokinase activity after 3-h
      incubation, and maximal effects are observed after 6 and 12 h of treatment. Using
      the bDNA assay, a sensitive signal amplification technique, we detected relative
      increases in glucokinase messenger RNA levels of 40.5 +/- 7.5% after 3-h
      incubation with cAMP. This stimulatory effect was increased to 106.3 +/- 22%
      after 6-h incubation and sustained up to 12 h of incubation. Inhibition of gene
      transcription by actinomycin D abolishes cAMP-induced glucokinase activity. In
      transfected fetal islets, cAMP increased the activity of the -1000 bp rat
      glucokinase promoter by 60 +/- 6%. These data demonstrate that cAMP has a
      stimulatory effect on pancreatic glucokinase gene expression and that the
      nucleotide has opposite effects on pancreatic and hepatic glucokinase, supporting
      the concept that glucokinase transcription in the liver and that in the beta-cell
      differ.

PMID- 11250925
TI  - Primary structure of a novel gonadotropin-releasing hormone in the brain of a
      teleost, Pejerrey.
AB  - The neuropeptide GnRH is the major regulator of reproduction in vertebrates
      acting as a first signal from the hypothalamus to pituitary gonadotropes. Three
      GnRH molecular variants were detected in the brain of a fish, pejerrey
      (Odontesthes bonariensis), using chromatographic and immunological methods. The
      present study shows that one form is identical to chicken GnRH-II (sequence
      analysis and mass spectrometry) and the second one is immunologically and
      chromatographically similar to salmon GnRH. The third form was proven to be a
      novel form of GnRH by isolating the peptide from the brain and determining its
      primary structure by chemical sequencing and mass spectrometry. The sequence of
      the novel pejerrey GnRH is pGlu-His-Trp-Ser-Phe-Gly-Leu-Ser-Pro-Gly-NH(2), which
      is different from the known forms of the vertebrate and protochordate GnRH
      family. The new form of GnRH is biologically active in releasing gonadotropin and
      GH from pituitary cells in an in vitro assay.

PMID- 11250926
TI  - XXY male mice: an experimental model for Klinefelter syndrome.
AB  - Klinefelter syndrome (47,XXY) is the most common sex chromosome aneuploidy in
      men. Thus, it is important to establish an experimental animal model to explore
      its underlying molecular mechanisms. Mice with a 41,XXY karyotype were produced
      by mating wild-type male mice with chimeric female mice carrying male embryonic
      stem cells. The objectives of the present study were to characterize the
      testicular phenotype of adult XXY mice and to examine the ontogeny of loss of
      germ cells in juvenile XXY mice. In the first experiment the testicular
      phenotypes of four adult XXY mice and four littermate controls (40,XY) were
      studied. XXY mice were identified by either Southern hybridization or karyotyping
      and were further confirmed by fluorescence in situ hybridization. The results
      showed that the testis weights of adult XXY mice (0.02 +/- 0.01 g) were
      dramatically decreased compared with those of the controls (0.11 +/- 0.01 g).
      Although no significant differences were apparent in plasma testosterone levels,
      the mean plasma LH and FSH levels were elevated in adult XXY mice compared with
      controls. The testicular histology of adult XXY mice showed small seminiferous
      tubules with varying degrees of intraepithelial vacuolization and a complete
      absence of germ cells. Hypertrophy and hyperplasia of Leydig cells were observed
      in the interstitium. Electron microscopic examination showed Sertoli cells
      containing scanty amounts of cytoplasm and irregular nuclei with prominent
      nucleoli. The junctional region between Sertoli cells appeared normal. In some
      tubules, nests of apparently degenerating Sertoli cells were found. In the second
      experiment the ontogeny of germ cell loss in juvenile XXY mice and their
      littermate controls was studied. Spermatogonia were found and appeared to be
      morphologically normal in juvenile XXY mice. Progressive loss of germ cells
      occurred within 10 days after birth. This resulted in the absence of germ cells
      in the adult XXY mice. We conclude that a progressive loss of germ cells
      occurring in early postnatal life results in the complete absence of germ cells
      in adult XXY mice. The XXY mouse provides an experimental model for its human XXY
      counterpart, Klinefelter syndrome.

PMID- 11250927
TI  - Regulation of calcitonin receptor by glucocorticoid in human osteoclast-like
      cells prepared in vitro using receptor activator of nuclear factor-kappaB ligand
      and macrophage colony-stimulating factor.
AB  - Using mouse osteoclast-like cells (OCs), we have shown that treatment with
      glucocorticoids (GCs) resulted in an increase in calcitonin (CT) binding by
      enhancing CT receptor (CTR) gene transcription. Additionally, treatment with GCs
      demonstrated increased sensitivity to CT. There is, however, scant information on
      the effects of GC or CTR regulation by GCs in human osteoclasts. In this study we
      examined CTR regulation by GCs and the effects of GCs and CT together in human
      OCs. OCs were prepared by treatment of peripheral blood mononuclear cells in
      vitro with soluble receptor activator of nuclear factor-kappaB ligand and
      macrophage colony-stimulating factor. Treatment of mature OCs with dexamethasone
      (Dex) resulted in a dose- and time-dependent increase in [(125)I]salmon CT (sCT)
      binding capacity. Treatment with Dex enhanced CTR messenger RNA (mRNA)
      expression, suggesting that CTR up-regulation is at least partly due to an
      increase in de novo CTR synthesis. Triamcinolone and prednisolone reproduced the
      Dex effect on [(125)I]sCT-specific binding and CTR mRNA expression, but 17beta
      estradiol, progesterone, dehydroepiandrosterone, and aldosterone did not. A
      Scatchard plot analysis showed that Dex enhanced CTR number with a minimal change
      in the affinity to sCT. Autoradiographic studies using [(125)I]sCT showed that
      Dex enhanced the CTR density on individual multinuclear OCs. Up-regulation of
      [(125)I]sCT-specific binding and CTR mRNA expression was seen even in the
      presence of sCT, but the enhancement diminished subsequently at later times (36
      48 h after sCT removal), which was consistent with our previous observation in
      mouse OCs. This suggests that GCs and CTs act on CTR expression differently,
      consistent with our previous work using mouse OCs, in which we found that GCs
      increased transcription of CTR gene expression, whereas CT reduced CTR mRNA
      stability. The results obtained in this study show that GC increased CTR
      expression and sensitivity to CT in cells of the human osteoclast lineage and
      provide the basis for understanding the beneficial effects of combination
      treatment with GCs and CTs in malignancy-associated hypercalcemia.

PMID- 11250928
TI  - Inability of overexpressed des(1-3)human insulin-like growth factor I (IGF-I) to
      inhibit forced mammary gland involution is associated with decreased expression
      of IGF signaling molecules.
AB  - Overexpression of des(1-3) human insulin-like growth factor I (IGF-I) in the
      mammary glands of transgenic mice (WAP-DES) inhibits apoptosis during natural,
      but not forced, mammary involution. We hypothesized that this differential
      response would correlate with the expression of IGF signal transducers. Forced
      and natural involution were analyzed in nontransgenic and WAP-DES mice beginning
      on day 16 postpartum. During natural involution, mammary gland wet weight was
      higher and apoptosis was lower in WAP-DES than in nontransgenic mice. The WAP-DES
      transgene had no effect on these parameters during forced involution. Mammary
      tissue concentrations of the transgene protein were 2- to 10-fold higher than
      those of endogenous IGF-I. Western blot analysis of pooled mammary tissue
      extracts demonstrated only slightly higher phosphorylation of the IGF signal
      transducers insulin receptor substrate-1 (IRS-1) and Akt in the WAP-DES than in
      nontransgenic mice. Dramatic early reductions in phospho-IRS-1, phospho-Akt, IRS
      1, IRS-2, and Akt proteins occurred during forced, but not natural, involution.
      The abundance of the IGF-I receptor and the messenger RNAs for the IGF-I
      receptors, IRS-1 and -2, were not affected by either genotype or involution.
      These findings support the conclusions that mammary cells lose their
      responsiveness to insulin-like signals during forced involution, and that
      posttranscriptional or posttranslational regulation of IRS-1 and IRS-2 may play a
      role in this loss.

PMID- 11250929
TI  - Angiotensin II induces skeletal muscle wasting through enhanced protein
      degradation and down-regulates autocrine insulin-like growth factor I.
AB  - We previously showed that angiotensin II (ang II) infusion in the rat produces
      cachexia and decreases circulating insulin-like growth factor I (IGF-I). The
      weight loss derives from an anorexigenic response and a catabolic effect of ang
      II. In these experiments we assessed potential catabolic mechanisms and the
      involvement of the IGF-I system in these responses to ang II. Ang II infusion
      caused a significant decrease in body weight compared with that of pair-fed
      control rats. Kidney and left ventricular weights were significantly increased by
      ang II, whereas fat tissue was unchanged. Skeletal muscle mass was significantly
      decreased in the ang II-infused rats, and a reduction in lean muscle mass was a
      major reason for their overall loss of body weight. In skeletal muscles, ang II
      did not significantly decrease protein synthesis, but overall protein breakdown
      was accelerated; inhibiting lysosomal and calcium-activated proteases did not
      reduce the ang II-induced increase in muscle proteolysis. Circulating IGF-I
      levels were 33% lower in ang II rats vs. control rats, and this difference was
      reflected in lower IGF-I messenger RNA levels in the liver. Moreover, IGF-I, IGF
      binding protein-3, and IGF-binding protein-5 messenger RNAs in the gastrocnemius
      were significantly reduced. To investigate whether the reduced circulating IGF-I
      accounts for the loss in muscle mass, we increased circulating IGF-I by
      coinfusing ang II and IGF-I, but this did not prevent muscle loss. Our data
      suggest that ang II causes a loss in skeletal muscle mass by enhancing protein
      degradation probably via its inhibitory effect on the autocrine IGF-I system.

PMID- 11250930
TI  - Constitutive expression of the steroid sulfatase gene supports the growth of MCF
      7 human breast cancer cells in vitro and in vivo.
AB  - Many human breast tumors are driven by high intratumor concentrations of 17beta
      estradiol that appear to be locally synthesized. The role of aromatase is well
      established, but the possible contribution of the steroid sulfatase (STS), which
      liberates estrogens from their biologically inactive sulfates, has been
      inadequately assessed and remains unclear. To evaluate the role of STS further,
      we transduced estrogen-dependent MCF-7 human breast cancer cells with a
      retroviral vector directing the constitutive expression of the human STS gene.
      Gene integration was confirmed by Southern hybridization, production of the
      appropriately sized messenger RNA by Northern hybridization, and expression of
      functional protein by metabolism of [(3)H]estrone sulfate to [(3)H]estrone.
      Maximum velocity estimates of estrone formation are 64.2 pmol estrone/mg
      protein.h in STS-transduced cells (STS Clone 20), levels comparable to those seen
      in some human breast tumors. Lower levels of endogenous activity are seen in MCF
      7 cells (13.0 pmol estrone/mg protein.h) and in cells transduced with vector
      lacking the STS gene (Vector 3 cells; 12.0 pmol estrone/mg protein.h). 17beta
      Estradiol sulfate induces expression of the progesterone receptor messenger RNA
      only in STS Clone 20 cells, whereas estrone sulfate produces the greatest
      stimulation of anchorage-independent growth in these cells. STS Clone 20 cells
      retain responsiveness to antiestrogens, which block the ability of estrogen
      sulfate to increase the proportion of cells in both the S and G(2)/M phases of
      the cell cycle. Consistent with these in vitro observations, only STS Clone 20
      cells exhibit a significant increase in the proportion of proliferating tumors in
      nude ovariectomized mice supplemented with 17beta-estradiol sulfate. The primary
      activity in vivo appears to be from intratumor STS, rather than hepatic STS.
      Surprisingly, 17beta-estradiol sulfate appears more effective than 17beta
      estradiol when both are administered at comparable concentrations. This effect,
      which is seen only in STS Clone 20 cells, may reflect differences in the cellular
      pharmacology of exogenous estrogens compared with those released by the activity
      of intracellular STS. These studies directly demonstrate that intratumor STS
      activity can support estrogen-dependent tumorigenicity in an experimental model
      and may contribute to the promotion of human breast tumors.

PMID- 11250931
TI  - Functional mapping of a placenta-specific upstream promoter for human
      gonadotropin-releasing hormone receptor gene.
AB  - GnRH has been showed to regulate hCG expression and secretion from the placenta
      through a GnRH receptor (GnRHR)-mediated process. Recently, we have reported the
      isolation of human GnRHR full-length complementary DNA from the human placental
      cells including choriocarcinoma JEG-3 cells, immortalized extravillous
      trophoblasts, and primary cultures of trophoblasts. Despite these observations,
      the molecular mechanism that controls the transcription regulation of the GnRHR
      gene expression in the placenta remains unknown. Here we described the
      identification of an upstream placenta-specific promoter located between
      nucleotide (nt) -1737 and -1346 (relative to the translation start site) for the
      human GnRHR gene. Using transient transfection studies, this upstream promoter
      has been shown to determine the placental cell-specific expression of this gene.
      Primer extension studies further confirmed the utilization of this promoter in
      JEG-3 cells in vivo. By mutagenesis coupled to functional studies, we have
      identified four putative transcription factor-binding sites, namely human
      glucocorticoid receptor (hGR)-Oct-1 (nt -1718 to -1710), hGR-cAMP response
      element (CRE; nt -1649 to -1641), hGR-GATA (nt -1602 to -1597), and hGR
      activating protein-1 (nt -1518 to -1511), that are essential to the expression of
      this gene. Mutations of these cis-acting motifs reduced the promoter activity.
      The CRE and GATA motifs were subsequently shown to be placenta specific, as
      mutations of these motifs caused a dramatic loss in promoter activities in the
      placental JEG-3 cells, but not in the ovarian carcinoma OVCAR-3, monkey kidney
      COS-1, and human embryonic kidney 293 cells. Gel mobility assays confirmed the
      binding of nuclear proteins Oct-1, CRE-binding protein, GATA-2, GATA-3, c-Fos,
      and c-Jun from JEG-3 cells to these four elements.

PMID- 11250932
TI  - High-level expression of a functional single-chain human chorionic gonadotropin
      luteinizing hormone receptor ectodomain complex in insect cells.
AB  - Reproductive capacity in primates is dependent on the high-affinity binding of
      the glycoprotein hormones LH and human (h)CG to the large ectodomain (ECD) of
      their common receptor (LHR). Our understanding of the precise molecular
      determinants of hormone binding is limited, because there are no structural data
      for any of the glycoprotein hormone receptors. Overexpression of the ECD of the
      receptor has been attempted in various expression systems. Prokaryotic expression
      does not yield properly folded ECD. Eukaryotic expression, on the other hand,
      results in mostly heterogeneous, intracellularly trapped protein, but the
      secreted ECD is completely folded. Accordingly, we have tethered the single-chain
      hormone, yoked hCG, to the N terminus of LHR-ECD (yoked hormone-extracellular
      domain). Yoked hCG is secreted at high levels; binds LHR with high affinity; and,
      when tethered to the N terminus of full-length LHR, it binds and constitutively
      activates the receptor. Using recombinant baculovirus, yoked hormone
      extracellular domain is secreted from insect cells at levels greater than 1
      microg/ml, nearly 20-fold higher than that previously reported in eukaryotic
      expression systems. The protein was purified and binds exogenous (125)I-hCG with
      high affinity but, significantly, only after protease treatment to remove the
      tethered hormone. Thus, the fusion protein seems to form a functional hormone
      receptor complex that is expressed at levels sufficient for its biophysical
      characterization.

PMID- 11250933
TI  - Sterol regulatory element binding protein-1a regulation of the steroidogenic
      acute regulatory protein gene.
AB  - The binding of tropic hormones to their specific receptors in steroidogenic cells
      stimulates the cAMP second-messenger system in the presence of steroidogenic
      factor-1 (SF-1) to increase expression of steroidogenic acute regulatory (StAR)
      protein, facilitating the transfer of cholesterol to the inner mitochondrial
      membrane. The increased use of cholesterol in steroidogenesis triggers activation
      of sterol- sensitive genes through a second regulatory pathway involving the
      binding of sterol regulatory element (SRE)-binding proteins (SREBP) to SREs
      located in the promoter regions of these genes. A search of the rat StAR promoter
      revealed five potential SRE sites, which demonstrated specific binding with
      recombinant SREBP-1a. Overexpression of SREBP-1a, -1c or -2 in HTB-9 cells
      cotransfected with the rat StAR promoter resulted in an increase in promoter
      driven luciferase activity. In addition, SREBP-1a was able to activate the StAR
      promoter through an E-box but only in a promoter construct lacking SREs. SREBPs
      are known to be weak transcriptional activators and require the presence of
      additional coactivators like Sp1 and nuclear factor-Y (NF-Y) to elicit maximum
      activation. Electrophoretic mobility shift assays demonstrated that Sp1, SF-1,
      and NF-Y enhanced SREBP-1a binding to SREs in the StAR promoter. There was a 4
      fold increase in StAR promoter luciferase reporter gene expression when HTB-9
      cells were cotransfected with expression vectors for SREBP-1a and NF-Y. In
      addition, the combined action of SREBP-1a and SF-1 increased both basal (1.6
      fold) and cAMP-induced (3.5-fold) activation of the rat StAR promoter. Although
      Sp1 enhanced SREBP-1a binding to an SRE, Sp1 was not able to increase StAR
      promoter activity in the presence of SREBP-1a. These results suggest that SREBP
      induced regulation of the rat StAR gene is responsive to selective combinations
      of transcriptional cofactors that could necessitate the convergence of multiple
      regulatory pathways to enhance gene transcription.

PMID- 11250934
TI  - Selective and nonselective inverse agonists for constitutively active type-1
      parathyroid hormone receptors: evidence for altered receptor conformations.
AB  - The spontaneous signaling activity of some G protein-coupled receptors and the
      capacity of certain ligands (inverse agonists) to inhibit such constitutive
      activity are poorly understood phenomena. We investigated these processes for
      several analogs of PTH-related peptide (PTHrP) and the constitutively active
      human PTH/PTHrP receptors (hP1Rcs) hP1Rc-H223R and hP1Rc-T410P. The N-terminally
      truncated antagonist PTHrP(5-36) functioned as a weak partial/neutral agonist
      with both mutant receptors but was converted to an inverse agonist for both
      receptors by the combined substitution of Leu(11) and D-Trp(12). The N-terminally
      intact analog [Bpa(2)]PTHrP(1-36)-a partial agonist with the wild-type hP1Rc-was
      a selective inverse agonist, in that it depressed basal cAMP signaling by hP1Rc
      H223R but enhanced signaling by hP1Rc-T410P. The ability of [Bpa(2)]PTHrP(1-36)
      to discriminate between the two receptor mutants suggested that H223R and T410P
      confer constitutive receptor activity by inducing distinct conformational
      changes. This hypothesis was confirmed by the observations that: 1) the double
      mutant receptor hP1Rc-H223R/T410P exhibited basal cAMP levels that were 2-fold
      higher than those of either single mutant; and 2) hP1Rc-H223R and hP1Rc-T410P
      internalized (125)I-PTHrP(5-36) to markedly different extents. The overall
      results thus reveal that two different types of inverse agonists are possible for
      PTHrP ligands (nonselective and selective) and that constitutively active PTH-1
      receptors can access different conformational states.

PMID- 11250935
TI  - Requirement of Sp1 and estrogen receptor alpha interaction in 17beta-estradiol
      mediated transcriptional activation of the low density lipoprotein receptor gene
      expression.
AB  - Estrogen is one of the most important physiological regulators of low density
      lipoprotein receptor (LDLR) expression. Despite many studies conducted in animals
      and humans showing increased expressions of LDLR messenger RNA by hormone
      treatment, the molecular basis of the effect of estrogen on LDLR transcription
      has not been clearly elucidated. By using HepG2 cells that transiently express
      functional estrogen receptor alpha (ERalpha) and LDLR promoter constructs, we
      show that the specific interaction of ERalpha with the transcription factor Sp1
      bound to the LDLR promoter is responsible for the activation of LDLR
      transcription by estrogen. We demonstrate that 1) mutations to abrogate the
      binding of Sp1 to its recognition sequences present in repeat 1 and repeat 3
      elements of the LDLR promoter completely abolish the ERalpha-mediated activation
      of the LDLR promoter activity; 2) mutations that abolish the selective DNA
      binding activity or inactivate the C-terminal transcription activation function
      (AF2) of ERalpha had no effect on the ability of ERalpha to activate LDLR
      transcription; however, transcriptional activation was completely lost by
      deletion of the N-terminal transcription activation region (AF1); 3) a subregion
      of AF1 (amino acids 67-139) was further identified to be important for ERalpha to
      activate the LDLR promoter; and 4) ERalpha enhanced the formation of Sp1-repeat 3
      DNA complexes. We also show that mutation at the sterol-responsive element-1 site
      diminishes the activity of ERalpha on LDLR transcription, thereby suggesting that
      the sterol-responsive element-1-binding protein may interact with the Sp1-ERalpha
      complex to trans-activate LDLR gene transcription. This study for the first time
      provides a molecular basis for an understanding of the regulation of LDLR
      transcription by estrogens.

PMID- 11250936
TI  - Adenosine triphosphate activates mitogen-activated protein kinase in human
      granulosa-luteal cells.
AB  - ATP has been shown to activate the phospholipase C/diacylglycerol/protein kinase
      C (PKC) pathway. However, little is known about the downstream signaling events.
      The present study was designed to examine the effect of ATP on activation of the
      mitogen-activated protein kinase (MAPK) signaling pathway and its physiological
      role in human granulosa-luteal cells. Western blot analysis, using a monoclonal
      antibody that detected the phosphorylated forms of extracellular signal-regulated
      kinase-1 and -2 (p42(mapk) and p44 (mapk), respectively), demonstrated that ATP
      activated MAPK in a dose- and time-dependent manner. Treatment of the cells with
      suramin (a P2 purinoceptor antagonist), neomycin (a phospholipase C inhibitor),
      staurosporin (a PKC inhibitor), or PD98059 (an MAPK/ERK kinase inhibitor)
      significantly attenuated the ATP-induced activation of MAPK. In contrast, ATP
      induced MAPK activation was not significantly affected by pertussis toxin (a G(i)
      inhibitor). To examine the role of G(s) protein, the intracellular cAMP level was
      determined after treatment with ATP or hCG. No significant elevation of
      intracellular cAMP was noted after ATP treatment. To determine the role of MAPK
      in steroidogenesis, human granulosa-luteal cells were treated with ATP, hCG, or
      ATP plus hCG in the presence or absence of PD98059. RIA revealed that ATP alone
      did not significantly affect the basal progesterone concentration. However, hCG
      induced progesterone production was reduced by ATP treatment. PD98059 reversed
      the inhibitory effect of ATP on hCG-induced progesterone production. To our
      knowledge, this is the first demonstration of ATP-induced activation of the MAPK
      signaling pathway in the human ovary. These results support the idea that the
      MAPK signaling pathway is involved in mediating ATP actions in the human ovary.

PMID- 11250937
TI  - The metastasis-associated metalloproteinase stromelysin-3 is induced by
      transforming growth factor-beta in osteoblasts and fibroblasts.
AB  - Bone matrix serves as a reservoir of growth factors important in growth and
      tissue remodeling, and transforming growth factor-beta (TGF-beta) is abundant in
      bone matrix. Normal processes, such as remodeling, and pathological processes,
      such as osteolytic metastasis, cause the release of growth factors from the
      matrix, allowing them to influence the behavior of cells within their
      microenvironment. Breast cancer metastases frequently establish themselves in the
      bone compartment, often causing localized osteolysis. Stromelysin-3 is a matrix
      metalloproteinase associated with tumor metastases. Its expression in host
      tissues favors the homing and survival of malignant epithelial cells in early
      tumorigenesis by releasing and/or activating growth factors sequestered in the
      extracellular matrix. Osteoblasts express stromelysin-3, and Northern and Western
      blot analysis show that its messenger RNA and protein levels are increased by TGF
      beta. Nuclear run-off assays demonstrate activation of gene transcription, and
      experiments using transcription inhibitors demonstrate stabilization of
      stromelysin-3 messenger RNA by TGF-beta. Importantly, TGFbeta induces stromelysin
      3 in fibroblasts by similar mechanisms, indicating that it is likely to stimulate
      stromelysin-3 expression in breast stroma. Stimulation of stromelysin-3
      expression by TGF-beta in fibroblasts and osteoblasts could play a role in the
      metastasis of breast cancer cells and their homing and survival in bone.

PMID- 11250938
TI  - Irradiation selectively inhibits expression from the androgen-dependent Pem
      homeobox gene promoter in sertoli cells.
AB  - How radiation blocks spermatogenesis in certain strains of rats, such as LBNF(1),
      is not known. Because the block depends on androgen, we propose that androgen
      affects Sertoli cell function in irradiated LBNF(1) rats, resulting in the
      failure of spermatogonial differentiation. To begin to identify genes that may
      participate in this irradiation-induced blockade of spermatogenesis, we
      investigated the expression of several Sertoli genes in response to irradiation.
      The expression of the PEM: homeobox gene from its androgen-dependent Sertoli
      specific proximal promoter (Pp) was dramatically reduced more than 100-fold in
      response to irradiation. In contrast, most other genes and gene products reported
      to be localized to the Sertoli cell, including FSH receptor (FSHR), androgen
      receptor (AR), SGP1, and the transcription factor CREB, did not exhibit
      significant changes in expression, whereas transferrin messenger RNA (mRNA)
      expression dramatically increased in response to irradiation. Irradiation also
      decreased Pp-driven PEM: mRNA levels in mouse testes (approximately 10-fold),
      although higher doses of irradiation than in rats were required to inhibit PEM:
      gene expression in testes of mice, consistent with their greater radioresistance.
      The decrease in Pem gene expression in mouse testis was also selective, as the
      expression of CREB, GATA-1, and SGP1 were little affected by irradiation. We
      conclude that the dramatic irradiation-triggered reduction of Pem expression in
      Sertoli cells is a conserved response that may be a marker for functional changes
      in response to irradiation.

PMID- 11250939
TI  - Natriuretic peptides suppress vascular endothelial cell growth factor signaling
      to angiogenesis.
AB  - Vascular endothelial cell growth factor (VEGF) is essential for angiogenesis.
      Atrial natriuretic peptide (ANP) inhibits the production of VEGF, but whether
      this important vascular peptide also inter- rupts VEGF signaling to angiogenesis
      is unknown. In cultured bovine aortic endothelial cells, VEGF significantly
      stimulated extracellular signal-regulated protein kinase activity and
      phosphorylation, which was inhibited 60% by coincubation with ANP or a
      natriuretic peptide clearance receptor specific ligand (NPRC), C-type NAP-(4-23)
      [C-ANP-(4-23)]. VEGF also stimulated c-Jun N-terminal kinase (JNK) and p38
      activities/phosphorylation that were prevented by the two natriuretic peptides
      (NP). A specific NP guanylate cyclase (GC) receptor antagonist, HS-142-1, blocked
      the actions of ANP [but not those of C-ANP-(4-23)], supporting the involvement of
      both GC and NPRC receptors. VEGF and expression of constituitively active JNK
      each stimulated the synthesis of cyclin D1 and increased the activity of the
      cyclin-dependent kinase-4, which was inhibited 55% by ANP. VEGF induced
      endothelial cell proliferation and migration, which was significantly blocked by
      NP or by expressing a dominant negative JNK-1. VEGF stimulated human
      microvascular endothelial cells to form capillary tubes, which was significantly
      inhibited by expressing dominant negative JNK-1 and by NP. Therefore, VEGF
      induction of critical steps in angiogenesis is enhanced through JNK activation.
      The actions are significantly prevented by NP, which act through both the NPRC
      and GC receptors to block growth factor signaling. Thus, NP are candidate
      antiangiogenesis factors that inhibit both the synthesis and function of VEGF.

PMID- 11250940
TI  - The serum- and glucocorticoid-induced kinase is a physiological mediator of
      aldosterone action.
AB  - Aldosterone plays a major role in regulating sodium and potassium flux in
      epithelial tissues such as kidney and colon. Recent evidence suggests that serum-
      and glucocorticoid-regulated kinase (SGK) is induced by aldosterone and acts as a
      key mediator of aldosterone action in epithelial tissues. Induction of SGK
      messenger RNA (mRNA) has previously been shown within 30 min of addition of
      supraphysiological doses of aldosterone to Xenopus A6 cells and within 4 h in rat
      kidney in vivo. In this study we determined the time course of SGK induction, at
      doses of aldosterone in the physiological range, in rat kidney and colon, using
      Northern and Western blot analyses and in situ hybridization and determined
      concurrent changes in urinary sodium and potassium excretion by Kagawa bioassay.
      On Northern blot analysis, SGK mRNA levels were significantly elevated in both
      kidney and colon 60 min after the injection of aldosterone. SGK protein in late
      distal colon was significantly elevated 2 and 4 h after aldosterone treatment. In
      situ hybridization showed SGK mRNA to be induced in renal collecting ducts and
      distal tubular elements in both cortex and medulla by doses of aldosterone of 0.1
      microg/100 g BW or more within 30 min of steroid treatment. Significant changes
      in urinary composition were similarly seen with an aldosterone dose of 0.1
      microg/100 g BW from 90 min after aldosterone injection. The early onset of SGK
      induction in kidney and colon and the correlation with urinary changes in terms
      of both time course and dose response suggest that SGK plays an important role in
      mediating the effects of aldosterone on sodium homeostasis in vivo.

PMID- 11250941
TI  - Rosiglitazone, insulin treatment, and fasting correct defective activation of
      protein kinase C-zeta/lambda by insulin in vastus lateralis muscles and
      adipocytes of diabetic rats.
AB  - Atypical protein kinases C (PKCs), zeta and lambda, and protein kinase B (PKB)
      are thought to function downstream of phosphatidylinositol 3-kinase (PI 3-kinase)
      and regulate glucose transport during insulin action in skeletal muscle and
      adipocytes. Insulin-stimulated glucose transport is defective in type II diabetes
      mellitus, and this defect is ameliorated by thiazolidinediones and lowering of
      blood glucose by chronic insulin therapy or short-term fasting. Presently, we
      evaluated the effects of these insulin-sensitizing modalities on the activation
      of insulin receptor substrate-1 (IRS-1)-dependent PI 3-kinase, PKC-zeta/lambda,
      and PKB in vastus lateralis skeletal muscles and adipocytes of nondiabetic and
      Goto-Kakizaki (GK) diabetic rats. Insulin provoked rapid increases in the
      activity of PI 3-kinase, PKC-zeta/lambda, and PKB in muscles and adipocytes of
      nondiabetic rats, but increases in IRS-1-dependent PI 3-kinase and PKC
      zeta/lambda, but not PKB, activity were substantially diminished in GK muscles
      and adipocytes. Rosiglitazone treatment for 10-14 days, 10-day insulin treatment,
      and 60-h fasting reversed defects in PKC-zeta/lambda activation in GK muscles and
      adipocytes and increased glucose transport in GK adipocytes, without necessarily
      increasing IRS-1-dependent PI 3-kinase or PKB activation. Our findings suggest
      that insulin-sensitizing modalities, viz. thiazolidinediones, chronic insulin
      treatment, and short-term fasting, similarly improve defects in insulin
      stimulated glucose transport at least partly by correcting defects in insulin
      induced activation of PKC-zeta/lambda.

PMID- 11250942
TI  - Glucocorticoid receptor-interacting protein-1 and receptor-associated coactivator
      3 differentially interact with the vitamin D receptor (VDR) and regulate VDR
      retinoid X receptor transcriptional cross-talk.
AB  - The vitamin D(3) receptor (VDR) is a ubiquitously expressed nuclear hormone
      receptor, and its ligand, calcitriol, has diverse biological effects. The extent
      to which transcriptional coactivators are involved in modulating tissue-specific
      functions of the VDR is unclear. Hence, the current studies investigated the role
      of p160 coactivators in regulating VDR function and interaction with RXR. Two
      p160 coactivators, glucocorticoid receptor-interacting protein-1 (GRIP1) and
      receptor-associated coactivator-3 (RAC3), which are expressed in an inverse
      fashion in cell lines representative of calcitriol target tissues, interacted
      directly with the VDR, both in vitro and in yeast cells, but only in the presence
      of calcitriol. Deletional analyses of VDR indicated that GRIP1 and RAC3 required
      an intact VDR activation function (AF-2) domain for efficient interaction as well
      as additional but distinct regions of the VDR. Coexpression experiments in yeast
      cells indicated that both GRIP1 and RAC3 coassemble with the VDR to form an
      active transcriptional complex. They also form ternary complexes with VDR
      homodimers and VDR:RXRalpha heterodimers. In mammalian cells, GRIP1 augmented VDR
      activation of the osteocalcin promoter, whereas RAC3 enhanced VDR activation
      indirectly through RXR. These data suggest different coactivators regulate VDR
      function via distinct mechanisms and support the hypothesis that the VDR recruits
      different coactivators depending on specific gene and cellular contexts.

PMID- 11250943
TI  - Early expression of pituitary adenylate cyclase-activating polypeptide and
      activation of its receptor in chick neuroblasts.
AB  - To investigate the involvement of pituitary adenylate cyclase- activating
      polypeptide (PACAP) and GH-releasing factor (GRF) during early chick brain
      development, we established neuroblast- enriched primary cell cultures derived
      from embryonic day 3.5 chick brain. We measured increases in cAMP generated by
      several species-specific forms of the peptides. Dose-dependent increases up to 5
      fold of control values were measured in response to physiological concentrations
      of human/salmon, chicken, and tunicate PACAP27. Responses to PACAP38 were more
      variable, ranging from 5-fold for human PACAP38 to 4-fold for chicken PACAP38, to
      no significant response for salmon PACAP38, compared with control values. The
      responses to PACAP38 may reflect a greater difference in peptide structure
      compared with PACAP27 among species. Increases in cAMP generated by human,
      chicken, and salmon/carp GRF were not statistically significant, whereas
      increases in response to lower-range doses of tunicate GRF27-like peptide were
      significant, but small. We also used immunocytochemistry and Western blot to show
      synthesis of the PACAP38 peptide. RT-PCR was used to demonstrate that messenger
      RNAs for PACAP and GRF and a PACAP-specific receptor were present in the cells.
      This is a first report suggesting an autocrine/paracrine system for PACAP in
      early chick brain development, based on the presence of the ligand, messages for
      the ligand and receptor, and activation of the receptor in neuroblast-enriched
      cultures.

PMID- 11250944
TI  - Distribution of galanin-like peptide in the rat brain.
AB  - Galanin-like peptide (GALP) is a novel galanin-like peptide isolated from the
      porcine hypothalamus. To determine the distribution of GALP in the rat brain, we
      performed immunohistochemical studies using a monoclonal antibody toward the N
      terminal sequence of GALP. GALP-immunoreactive neuronal cell bodies were observed
      only in the arcuate nucleus (Arc), which was further confirmed by in situ
      hybridization studies using digoxigenin-labeled antisense GALP riboprobe.
      Additional immunostained cells were found in the median eminence and infundibular
      stalk. The GALP neurons found in the Arc were further characterized by double
      label immunohistochemistry. More than 85% of the GALP neurons were immunostained
      with leptin receptor antibody. However, the GALP neurons and fibers found in the
      Arc were not labeled with alpha-MSH, somatostatin, neuropeptide Y, agouti-related
      protein, or galanin antibodies, indicating that GALP is found in neurons other
      than these known Arc neurons. Dense staining of GALP-containing fibers was found
      in the anterior parvicellular part of the paraventricular hypothalamic nucleus,
      in the ventral part of the lateral septal nucleus, and in the bed nucleus of the
      stria terminalis. Relatively dense staining was noted in the medial preoptic area
      (MPA), and weak staining was noted in the periventricular hypothalamic nucleus.
      Detailed double labeling studies in the paraventricular hypothalamic nucleus
      demonstrated that GALP-containing fibers converged in a more rostral direction
      than did agouti-related protein-containing fibers. Furthermore, GALP
      immunoreactive fibers were in close apposition with GnRH-immunoreactive fibers in
      the MPA and bed nucleus of the stria terminalis, and about 6% of GnRH-positive
      neurons in the MPA showed close contact with the GALP-immunoreactive fibers. Our
      findings indicate that GALP neurons, as leptin-responsive neurons, may
      participate in the regulation of feeding behavior and/or reproductive functions.

PMID- 11250945
TI  - Insulin deprivation leads to deficiency of Sp1 transcription factor in H-411E
      hepatoma cells and in streptozotocin-induced diabetic ketoacidosis in the rat.
AB  - Members of the family of Sp transcription factors include Sp1, Sp3, and Sp4 and
      are important regulators of eukaryotic gene expression. We previously reported
      that Sp1 mediated stimulation of rat calmodulin I gene expression in response to
      insulin. To test whether other members of the Sp family are direct targets of
      insulin action, we compared the levels of Sp1 and Sp3 proteins from nuclear
      extracts obtained from both insulin-treated and untreated rat hepatoma (H-411E)
      cells. We demonstrated by Western blot analysis that levels of Sp1 and Sp3
      proteins were increased more than 2-fold in the insulin-treated group.
      Additionally, the up-regulation of both Sp1 and Sp3 transcription factors by
      insulin was antagonized by tumor necrosis factor-alpha, a known inhibitor of
      insulin action. Immunohistochemical analysis demonstrated that H-411E cells
      treated with insulin (10,000 microU/ml) had a marked increase in demonstrable Sp1
      in the nucleus compared with cells incubated in insulin-free medium. We extended
      these in vitro observations to in vivo studies in the streptozotocin-diabetic rat
      model. We demonstrated in rat liver tissue by both Western blot and
      immunohistochemical staining with anti-Sp1 antibody that 1) livers of fully
      diabetic streptozotocin rats have low levels of Sp1 transcription factor; and 2)
      insulin treatment of the diabetic rat rapidly reversed this process by markedly
      stimulating accumulation of Sp1 in rat liver. Studies of the signal transduction
      mechanisms involved in insulin's effect on Sp1 demonstrate a facilitating role
      for phosphoinositol 3-kinase and an inhibitory role for cyclic nucleotides. In
      summary, insulin stimulates Sp1 protein, a transcription factor that is shown to
      regulate calmodulin gene expression and most likely other, as yet untested,
      genes.

PMID- 11250946
TI  - Light and electron microscopy localization of the 11beta-hydroxysteroid
      dehydrogenase type I enzyme in the rat.
AB  - The 11beta-hydroxysteroid dehydrogenase type I enzyme (11betaHSD1) converts
      cortisone to cortisol in humans, and 11-dehydrocorticosterone to corticosterone
      in rodents. In the present study we used a new immunopurified polyclonal
      antibody, RAH113, to localize 11betaHSD1 at the light and electron microscopy
      levels in a wide range of rat tissues. 11betaHSD1 staining in the liver was of
      highest intensity around the central vein and decreased radially. In the lung,
      11betaHSD1 was found at highest levels in the interstitial fibroblast, with
      levels in the type II pneumocyte an order of magnitude lower. RAH113 stained
      proximal tubules of the renal cortex and interstitial cells of the medulla and
      papilla. Adrenal 11betaHSD1 was confined to the glomerulosa and medulla, whereas
      the glucocorticoid-inactivating hydroxysteroid dehydrogenase isoform 11betaHSD2
      was present in fascilulata/reticularis. 11betaHSD1 was found in parietal cells of
      the fundic region of the stomach, but not in the antrum. In the heart, 11betaHSD1
      was detected in cells resembling interstitial fibroblasts of the endocardium and
      in the adventitial fibroblasts of blood vessels. Western blot analysis confirmed
      the presence of an antigen of the correct size (34 kDa) and intensity consistent
      with levels of enzyme activity previously reported in these tissues. Brain and
      testis also displayed the 34-kDa protein, confirming the expression of authentic
      11betaHSD1 in these tissues. Electron microscopy of lung and kidney interstitial
      cells showed that 11betaHSD1 was localized both to the endoplasmic reticulum and
      the nuclear membrane. These results show that 11betaHSD1 is present in discrete
      cell populations where it may facilitate intracrine and paracrine glucocorticoid
      action in addition to its classical role of maintaining circulating
      glucocorticoids via activity in the liver.

PMID- 11250947
TI  - In vivo expression of insulin-like growth factor-binding protein-2 in human
      gliomas increases with the tumor grade.
AB  - Human central nervous system tumors and glioma cell lines highly express the
      insulin-like growth factor-binding protein (IGFBP)-2. As IGFBP-2 can affect tumor
      growth, we studied the relationship between IGFBP-2 expression and the malignancy
      of brain tumors in vivo. To do so, we investigated by immunohistochemistry the
      accumulation of IGFBP-1, -2, and -3 in 50 human gliomas classified by the WHO
      Malignancy Scale. Double labeling using anti-CD68 (monocytes/macrophages),
      antiglial fibrillary acidic protein, and anti-CD3 (T cells) antibodies was
      performed to further characterize the IGFBP-1, -2, and -3(+) cells. The
      expression of IGFBP messenger RNAs (mRNAs) was tested by RT-PCR in tumor samples
      from nine gliomas of different grades and in eight cell lines representing the
      cellular composition of human glioma. As controls, the accumulation of IGFBP-2
      was investigated in normal brain and in the rat C6 glioblastoma model. IGFBP-1
      and -3 accumulated in endothelial and macrophage/microglial cells. IGFBP-2(+)
      macrophage/microglial and glioma cells clustered in the immediate vicinity of
      focal necrosis of the human gliomas as well as of the rat C6 glioblastoma. The
      labeling score of IGFBP-1 accumulation in endothelial cells correlated negatively
      (P: = 0.0229), and that of IGFBP-2 accumulation in glioma cells correlated
      positively (P: < 0.0006) with the tumor grade of the gliomas. In addition, RT-PCR
      analysis confirmed mRNA expression of IGFBP-1, -2, and -3 by the gliomas and
      glial cells. Small amounts of IGFBP-1 and -3 mRNA, but high amounts of IGFBP-2
      mRNA, were detectable in macrophage-like and glioma cell lines. The results
      suggest cell type-specific accumulation of IGFBP-1, -2, and -3 in human glial
      tumors of the brain. The increase in IGFBP-2 expression with this malignancy
      suggests a role of IGFBP-2 in the biology of human gliomas.

PMID- 11250948
TI  - Immunohistochemical localization of the vasopressin V1b receptor in the rat brain
      and pituitary gland: anatomical support for its involvement in the central
      effects of vasopressin.
AB  - Biological effects of vasopressin (VP) are mediated by four different receptors,
      two of which (the V1a and the oxytocin receptors) have been well characterized in
      the rodent brain, suggesting that these are the main receptors responsible for
      the central effects of VP. However, transcripts of the V1b VP receptor (V1bR)
      have been detected throughout the rat brain by RT-PCR and in situ hybridization,
      indicating that the V1bR adds to the population of central VP receptors. Because
      there are no specific ligands for the V1bR, the receptor protein itself has been
      difficult to visualize. In the present study, the distribution of the V1bR
      protein was investigated in the rat forebrain, midbrain, hindbrain, and
      cerebellum by immunohistochemistry using an antiserum raised against a synthetic
      fragment of the carboxylterminal of the rat V1bR protein. Immunohistochemistry
      revealed the presence of the V1bR in pituitary corticotrophs as expected. In
      naive, untreated rats, fiber networks containing V1bR-immunoreactivity were
      mainly concentrated in the hypothalamus, amygdala, cerebellum, and particularly
      in those areas with a leaky blood brain barrier or close to the circumventricular
      organs (medial habenula, subfornical organ, organum vasculosum laminae
      terminalis, median eminence, and nuclei lining to the third and fourth
      ventricles). A strikingly dense network was present in the external zone of the
      median eminence. Colchicine treatment was required to reveal the localization of
      V1bR-immunoreactive cell bodies. V1bR-containing cell bodies and associated
      protrusions were mainly located in the hippocampus, caudate putamen, cortex,
      thalamus, olfactory bulb, and cerebellum. These results demonstrate the
      widespread distribution of the V1bR protein in the rat brain over multiple,
      functionally distinct neuronal systems. These data suggest that the V1bR mediates
      different physiological functions of VP in the brain.

PMID- 11250949
TI  - Estradiol signaling via sequestrable surface receptors.
AB  - Estradiol (E(2))-signaling is widely considered to be exclusively mediated
      through the transcription-regulating intracellular estrogen receptor (ER) alpha
      and ERbeta. The aim of this study was to investigate transcription-independent
      E(2)-signaling in mouse IC-21 macrophages. E(2) and E(2)-BSA induce a rapid rise
      in the intracellular free Ca(2+) concentration ([Ca(2+)](i)) of Fura-2 loaded IC
      21 cells as examined by spectrofluorometry. These changes in [Ca(2+)](i) can be
      inhibited by pertussis toxin, but not by the ER-blockers tamoxifen and
      raloxifene. The E(2)-signaling initiated at the plasma membrane is mediated
      through neither ERalpha nor ERbeta, but rather through a novel G protein-coupled
      membrane E(2)-receptor as revealed by RT-PCR, flow cytometry, and confocal laser
      scanning microscopy. A special feature of this E(2)-receptor is its sequestration
      upon agonist stimulation. Sequestration depends on energy and temperature, and it
      proceeds through a clathrin- and caveolin-independent pathway.

PMID- 11250950
TI  - Cytokine-activated endothelium recruits osteoclast precursors.
AB  - Osteoclast precursors reach sites of osteoclast formation and remodelling via the
      vasculature and are therefore destined to encounter endothelium before migrating
      to the bone surface. Here we investigated the hypothesis that endothelium may be
      involved in the regulation of osteoclast precursor recruitment to sites of bone
      resorption. Osteoclast precursors in human peripheral blood were identified by
      their ability to form mature osteoclasts in 21-day cultures supplemented with
      RANKLigand, M-CSF, 1,25(OH)(2)-vitamin D(3), dexamethasone and prostaglandin
      E(2). Under control conditions few osteoclast precursors adhered to endothelial
      cells (the human bone marrow-derived endothelial cell line BMEC-1). However, BMEC
      1 cells treated with the resorption stimulating cytokines IL-1beta and TNFalpha
      depleted the PBMC population of all osteoclast precursors. These results provide
      the first evidence that osteoclast precursors can adhere to endothelium and
      suggest that endothelium could play an important role in the recruitment of
      osteoclast precursors to sites of bone resorption.

PMID- 11250951
TI  - Prevention of contrast nephropathy after cardiac catheterisation.

PMID- 11250952
TI  - The "angioplastically correct" follow up strategy after stent implantation.

PMID- 11250953
TI  - Acute aortic syndrome.

PMID- 11250955
TI  - A rehabilitative approach to patients with internal cardioverter-defibrillators.

PMID- 11250954
TI  - Detection and significance of subclinical mitral regurgitation by colour Doppler
      techniques.

PMID- 11250956
TI  - How different from pacemaker patients are recipients of implantable cardioverter
      defibrillators with respect to psychosocial adaptation, affective disorders, and
      quality of life?
AB  - OBJECTIVE: To assess differences in psychosocial adaptation, quality of life, and
      incidence of affective disorders between patients with pacemakers and those with
      implantable cardioverter-defibrillators (ICDs). DESIGN: Patients aged 40-70 years
      who underwent a first pectoral implantation of a pacemaker or an ICD system were
      studied. All subjects were asked to complete the hospital anxiety and depression
      scale (HAD), the short form general health survey (SF-36), and a specially
      designed device related questionnaire. Data analysis was performed for three
      patient groups: pacemaker (n = 76), ICD patients who received therapeutic shocks
      (n = 45), and ICD patients who did not receive shocks (n = 31). RESULTS: There
      were no differences between the three patient groups in HAD scores or in any of
      the SF-36 subscales or summary ratings. Probable depressive disorder (depression
      score > 10) was observed in 5.2%, 6.5%, and 6.6%, and probable anxiety disorder
      (anxiety score > 10) in 13.1%, 9.7%, 13.3% of the pacemaker, non-shocked ICD, and
      shocked ICD patients, respectively. There were no sex differences. However,
      patients in the shocked ICD group were more likely than those in the other groups
      to report limitations in their leisure activities, to perceive their device as a
      "life extender," and to admit anxiety about battery depletion and technical
      problems. Forty per cent of shocked ICD patients would be interested in joining a
      support group. CONCLUSIONS: Despite having distinctly different medical histories
      and treatments, patients with pacemakers and ICDs responded similarly to
      validated tools of health status assessment. ICD patients who had received shocks
      perceived their device as prolonging their life and had greater anxiety about
      technical problems. Their endorsement of the potential benefits of a support
      group warrants further investigation.

PMID- 11250957
TI  - Acute and convalescent changes in plasma homocysteine concentrations in acute
      coronary syndromes.
AB  - BACKGROUND: Raised plasma homocysteine is a risk factor for coronary artery
      disease. Patients with myocardial infarction or unstable angina show greater
      activation of coagulation, greater troponin release, and a worse outcome.
      OBJECTIVE: To examine variations in plasma homocysteine concentration in relation
      to C reactive protein (CRP) in patients presenting with acute coronary syndromes.
      METHODS: Consecutive patients presenting with acute myocardial infarction (22)
      and unstable angina pectoris (12) were studied. Plasma samples were obtained on
      admission (before clinical intervention), on days 2, 7, and 28, and again six
      months after admission. Plasma homocysteine, assayed by high performance liquid
      chromatography, and CRP were both determined at the same time points. Changes
      were assessed by analysis of variance. RESULTS: CRP concentrations showed a
      classical rise on day 2, followed by a gradual decline to normal values taken at
      six months from admission in both myocardial infarction (p < 0.0001) and unstable
      angina (p = 0.02). Homocysteine concentrations in myocardial infarction (median,
      25th to 75th interquartile range) were: 11.9 (10.7 to 12.6), 11.5 (9.1 to 13.4),
      12.1 (11.4 to 14.1), 12.4 (11.1 to 14.4), and 12.1 (11.2 to 14.0) micromol/l, for
      days 1, 2, 7, 28, and 180, respectively (p = 0.02). Significant differences were
      observed only between day 2 and day 7 (p < 0.05). The final homocysteine
      measurement was not different from the admission level. Homocysteine
      concentrations in unstable angina did not differ between admission and
      convalescence (12.5 (9.1 to 14.5) micromol/l and 12.3 (7.7 to 14.9) micromol/l,
      respectively). CONCLUSIONS: Plasma homocysteine concentrations are minimally
      influenced by acute phase variations with reliable measurements obtained on
      admission in patients with myocardial infarction and unstable angina.

PMID- 11250958
TI  - A subtle sign of aortic outflow obstruction in an infected 29 year old Starr
      Edward's valve.

PMID- 11250959
TI  - Psychological characteristics and fatal ischaemic heart disease.
AB  - OBJECTIVE: To determine the relation between psychological characteristics and
      subsequent fatal ischaemic heart disease (IHD) events. DESIGN: Prospective study
      of participants in the Northwick Park heart study (NPHS) recruited between 1972
      and 1978 and followed up for fatal events until 1997. SETTING: Three occupational
      groups in north west London. SUBJECTS: 1408 white men without a history of
      myocardial infarction aged 40-64 years at entry who completed a Crown-Crisp
      experiential index form (CCEI). MAIN OUTCOME MEASURE: Fatal IHD during follow up.
      RESULTS: A one point increase in the score on the obsessionality/obsessional
      neurosis subscale was associated with a relative risk of fatal IHD of 1.08 (95%
      confidence interval (CI) 1.02 to 1.15). For the functional somatic complaint
      subscale the relative risk was also 1.08 (95% CI 1.02 to 1.15). In the case of
      the total score the relative risk of fatal IHD was 1.28 (95% CI 1.09 to 1.50) for
      a 10 point increase. The associations were independent of age, social class, and
      known cardiovascular risk factors. In the case of phobic anxiety, which had
      previously been found to be associated with fatal IHD in NPHS, the association
      was evident in the first 10 years of follow up but overall the relative risk was
      only 1.07 (95% CI 0.99 to 1.15) for a one point increase in the score.
      CONCLUSION: Scores on two of the subscales of the CCEI and the total score are
      significantly associated with fatal IHD on long term follow up independently of
      other known risk factors.

PMID- 11250960
TI  - T wave alternans: an electrocardiographic sign of cardiac instability.

PMID- 11250961
TI  - Socioeconomic differentials in recurrent ischaemia and mortality after acute
      myocardial infarction.
AB  - OBJECTIVE: To examine the influence of socioeconomic deprivation on case fatality
      following acute myocardial infarction. DESIGN: Prospective cohort observational
      study. SETTING: General hospital. PATIENTS: 1417 white and south Asian patients
      admitted with acute myocardial infarction between January 1988 and December 1996,
      and classified by the Carstairs socioeconomic deprivation score of the
      enumeration district of residence. MAIN OUTCOME MEASURES: 30 day and one year
      survival. RESULTS: There was little variation across deprivation groups in age,
      sex, or smoking status, though a higher proportion of patients from more deprived
      enumeration districts were diabetic and of south Asian origin, and a higher
      proportion of them developed Q wave infarction and left ventricular failure.
      There was no appreciable variation in clinical treatment with deprivation.
      Patients from more deprived enumeration districts had a higher risk of recurrent
      ischaemic events (death, recurrent myocardial infarction, or unstable angina)
      over the first 30 days: event free survival (95% confidence interval (CI)) of the
      most deprived quartile was 0.79 (95% CI 0.74 to 0.83) compared with 0.85 (95% CI
      0.80 to 0.88) in the least deprived quartile. The unadjusted hazard ratio
      corresponding to an increase from the 5th to 95th centile of the deprivation
      distribution was 1.54 (95% CI 1.02 to 2.32), and 1.59 (95% CI 1.03 to 2.44) after
      adjustment for age, sex, racial group, diabetes, acute treatment with
      thrombolysis and aspirin, and left ventricular failure. Survival from 30 days to
      one year, however, did not show a socioeconomic gradient (hazard ratio adjusted
      for the same variables was 1.07 (95% CI 0.68 to 1.70)). CONCLUSIONS: In patients
      hospitalised with acute myocardial infarction, there is a strong association
      between early recurrent ischaemic events and socioeconomic deprivation that is
      not accounted for by clinical presentation or treatment. This association appears
      to be attenuated over time.

PMID- 11250963
TI  - Bilateral Winslow's pathways.

PMID- 11250962
TI  - A new performance indicator for acute myocardial infarction.
AB  - OBJECTIVE: To develop a performance indicator for acute myocardial infarction
      which would reliably measure success of treatment and which might provide an
      alternative to case fatality as an audited outcome. DESIGN: A two year audit of
      all cases of acute myocardial infarction and resuscitated cases of out of
      hospital cardiac arrest from coronary heart disease in patients under 75 years of
      age. Behaviour of patients in calling for help, performance of the ambulance
      services in treating out of hospital arrest, and of the hospitals in providing
      resuscitation and thrombolytic treatment are audited separately. SETTING: Four
      district general hospitals. AUDITED INTERVENTIONS: Resuscitation from cardiac
      arrest and thrombolytic treatment. MAIN OUTCOME MEASURES: Hospital case fatality
      and lives saved/1000 patients treated. RESULTS: Overall, the lives of 83/1000
      patients were saved (95% confidence interval 70 to 96). Of these, 29 (35%) were
      saved by out of hospital resuscitation and 38 (46%) by in hospital resuscitation
      from cardiac arrest. It was estimated that 16 lives (19%) were saved by
      thrombolytic treatment. There were no significant differences in case fatality
      among the hospitals. CONCLUSIONS: Lives saved/1000 patients treated is an easily
      measurable index and assesses performance of the ambulance service as well as of
      the hospital. Because it is relatively insensitive to diagnostic definitions, it
      may provide a robust alternative to case fatality as a performance indicator.

PMID- 11250965
TI  - A combination of persistent left superior vena cava and a large secundum atrial
      septal defect in a 34 year old woman.

PMID- 11250964
TI  - Lesion characteristics of acute myocardial infarction: an investigation with
      intravascular ultrasound.
AB  - OBJECTIVE: To use intravascular ultrasound (IVUS) to compare plaque morphology in
      acute myocardial infarction and stable angina pectoris. DESIGN: Retrospective
      study. SETTING: Primary care hospital. PATIENTS: 59 consecutive cases of acute
      myocardial infarction and 50 consecutive cases of stable angina pectoris.
      METHODS: IVUS was used before coronary intervention. MAIN OUTCOME MEASURES:
      Plaque morphology (incidence of eccentric plaque, subtle dissections, low echoic
      thrombus, calcification, echolucent areas, and bright speckled echo material),
      assessed visually using IVUS. RESULTS: There were no significant differences in
      plaque eccentricity or calcification between the two groups, but low echoic
      thrombus (acute myocardial infarction 15% v stable angina pectoris 0%), subtle
      dissections (37% v 4%), echolucent areas (31% v 0%), and bright speckled echo
      material (90% v 0%) were more common in the infarction group than in the stable
      angina group (p < 0.001 for all). There was a longer time between the onset of
      symptoms and the IVUS examination in patients with low echoic thrombus than in
      those without (p < 0.03). CONCLUSIONS: Low echoic thrombus, subtle dissections,
      echolucent areas, and bright speckled echo material are morphological
      characteristics associated with plaque at the time of acute myocardial
      infarction. These findings correspond pathologically to ruptured plaque.

PMID- 11250967
TI  - Electromechanical interrelations during dobutamine stress in normal subjects and
      patients with coronary artery disease: comparison of changes in activation and
      inotropic state.
AB  - OBJECTIVE: To identify the effects of altered ventricular activation during
      dobutamine stress on left ventricular function in normal subjects and in patients
      with coronary artery disease, and to distinguish these from an inotropic
      response. DESIGN: Prospective analysis of 12 lead ECG and echocardiogram at rest
      and at peak stress. SETTING: Tertiary referral centre for cardiac disease
      equipped with non-invasive facilities for pharmacological stress testing.
      METHODS: 22 patients with coronary artery disease were compared with 17 age
      matched controls. Left ventricular ejection and filling patterns were assessed
      using Doppler echocardiography. Activation effects were correlated with relative
      left ventricular ejection and filling times, and the Z ratio ([left ventricular
      ejection + filling times]/RR interval). Inotropic response was measured from peak
      aortic acceleration. RESULTS: In controls, QRS shortened (by 4 ms, p < 0.001),
      and total ejection and filling periods lengthened (by 2 s/min, p < 0.01 and 5
      s/min, p < 0.001, respectively). The Z ratio thus increased and correlated with
      QRS shortening (r(2) = 0.69). Peak aortic acceleration (PAA) increased by 135%, p
      < 0.001. In patients, QRS lengthened at peak stress (by 9 ms, p < 0.001). Total
      ejection and filling times did not change, but Z ratio fell, correlating with QRS
      prolongation (r(2) = 0.65). Nevertheless, PAA increased by 63%, p < 0.001.
      CONCLUSIONS: Relative ejection and filling times reflect ventricular activation
      at rest and during stress independent of changes in inotropic state. By contrast,
      peak aortic acceleration reflects the positive inotropic effect of dobutamine on
      the myocardium, regardless of changes in activation.

PMID- 11250966
TI  - Prospective comparison of clinical and echocardiographic diagnosis of rheumatic
      carditis: long term follow up of patients with subclinical disease.
AB  - OBJECTIVE: To determine the frequency of occurrence and long term evolution of
      subclinical carditis in patients with acute rheumatic fever. DESIGN: Valvar
      incompetence was detected by clinical examination and Doppler echocardiographic
      imaging during the acute and quiescent phases of rheumatic fever. Patients were
      followed prospectively and submitted to repeat examinations at one and five years
      after the acute attack. Persistence of acute mitral and aortic lesions detected
      solely by echocardiography (subclinical disease) was compared with that of
      disease detected by clinical examination as well (thereby fulfilling the latest
      1992 Jones criteria for rheumatic carditis). SETTING: Three general hospitals
      with a university affiliation in Chile. PATIENTS: 35 consecutive patients
      fulfilling the revised Jones criteria for rheumatic fever. Clinical and
      echocardiographic examination was repeated in 32 patients after one year and in
      17 after five years. Ten patients had subclinical carditis on admission, six of
      whom were followed for five years. MAIN OUTCOME MEASURES: Auscultatory and
      echocardiographic evidence of mitral or aortic regurgitation during the acute
      attack or at follow up. RESULTS: Mitral or aortic regurgitation was detected by
      Doppler echocardiographic imaging in 25/35 rheumatic fever patients as opposed to
      5/35 by clinical examination (p = 0.03). Doppler echocardiography revealed acute
      valvar lesions in 10 of 20 rheumatic fever patients who had no auscultatory
      evidence of rheumatic carditis (subclinical carditis). Three of these subclinical
      lesions and three of the clinical or auscultatory lesions detected on admission
      were still present after five years of follow up, emphasising that subclinical
      lesions are not necessarily transient. CONCLUSIONS: Doppler echocardiographic
      imaging improves the detection of rheumatic carditis. Subclinical valve lesions,
      detected only by Doppler imaging, can persist. Echocardiographic findings should
      be accepted as a major criterion for the diagnosis of rheumatic fever.

PMID- 11250968
TI  - Incremental prognostic value of stress echocardiography as an adjunct to exercise
      electrocardiography after uncomplicated myocardial infarction.
AB  - OBJECTIVE: To assess the prognostic value of stress echocardiography as an
      adjunct to exercise electrocardiography in patients with uncomplicated acute
      myocardial infarction. DESIGN: 496 patients underwent a maximum exercise ECG and
      pharmacological stress echocardiography (406 dobutamine and 90 dipyridamole)
      within 15 days of uncomplicated acute myocardial infarction and were followed for
      a mean of 25 months (range 1-74 months) for reinfarction, unstable angina, and
      cardiac death. Patients undergoing revascularisation were omitted. RESULTS:
      Exercise ECG was positive in 162 patients (32.6%) and low threshold positive (<
      100 W) in 91 (18%). Stress echocardiography was positive in 239 patients (48%)
      (194 with dobutamine and 45 with dipyridamole stress). The agreement between the
      two tests was 63% (kappa = 0.24, 95% confidence interval 0.15 to 0.33). Sixty
      nine spontaneous events occurred (14 cardiac deaths, 26 reinfarctions, and 29
      with unstable angina requiring hospital admission), and 126 patients underwent
      revascularisation (39 coronary angioplasty and 87 bypass surgery). By receiver
      operating characteristic curve analysis, stress echocardiography provided
      incremental prognostic information compared with clinical data. A low threshold
      positive exercise ECG was associated with a worse outcome, but there was a
      fivefold increase in risk in patients with positive stress echocardiography who
      also had a high threshold (> 100 W) positive exercise ECG. Event-free survival of
      patients with both tests positive was significantly less than in patients with
      only one positive test or with both tests negative. CONCLUSIONS: Stress
      echocardiography provides additional prognostic information after uncomplicated
      acute myocardial infarction, but the greatest gain is found in patients with a
      high threshold positive exercise ECG.

PMID- 11250969
TI  - Exercise induced widening of the QRS complex in a patient on flecainide.

PMID- 11250970
TI  - Class IC antiarrhythmic drug induced atrial flutter: electrocardiographic and
      electrophysiological findings and their importance for long term outcome after
      right atrial isthmus ablation.
AB  - OBJECTIVE: To describe the electrocardiographic and electrophysiological findings
      of new atrial flutter developing in patients taking class IC antiarrhythmic drugs
      for recurrent atrial fibrillation, and to report the long term results of right
      atrial isthmus ablation in relation to the ECG pattern of spontaneous atrial
      flutter. DESIGN: Retrospective analysis. SETTING: Tertiary care academic
      hospital. PATIENTS: 24 consecutive patients with atrial fibrillation (age 54 (12)
      years; 5 female, 19 male) developing atrial flutter while taking propafenone (n =
      12) or flecainide (n = 12). RESULTS: The ECG was classified as typical (n = 13;
      54%) or atypical atrial flutter (n = 8) or coarse atrial fibrillation (n = 3).
      Counterclockwise atrial flutter was the predominant arrhythmia. Acute success
      after isthmus ablation was similar in patients with typical (12/13) and atypical
      (8/8) atrial flutter. After long term follow up (13 (6) months, range 6-26
      months), continuation of antiarrhythmic drug treatment appeared to result in
      better control of recurrences of atrial fibrillation in patients with typical
      atrial flutter (11/13) than in those with atypical atrial flutter (4/8), but the
      difference was not significant. Ablation for coarse atrial fibrillation was
      unsuccessful. CONCLUSIONS: New atrial flutter developing in patients taking class
      IC antiarrhythmic drugs for recurrent atrial fibrillation has either typical or
      atypical flutter wave morphology on ECG. The endocardial activation pattern and
      the acute results of ablation suggest that the flutter circuit was located in the
      right atrium and that the isthmus was involved in the re-entry mechanism. There
      appeared to be better long term control of recurrent atrial fibrillation in
      patients with typical (85%) as compared with atypical atrial flutter (50%).
      Patients developing coarse atrial fibrillation may not be candidates for this
      strategy.

PMID- 11250971
TI  - Mitral regurgitation after anthracycline treatment for childhood malignancy.
AB  - OBJECTIVE: To investigate the new onset of mitral regurgitation in patients with
      otherwise normal echocardiograms after anthracycline treatment and to assess its
      relation to other selected indicators of myocardial damage. DESIGN: Prospective
      echocardiographic and electrocardiographic study. SETTING: Tertiary paediatric
      cardiac referral centre. PATIENTS: 305 patients, aged 2-33 years (median 14
      years), treated with cumulative anthracycline doses of between 150-450 mg/m(2)
      (median 180 mg/m(2)) for childhood malignancy. MAIN OUTCOME MEASURES: Colour flow
      Doppler detection of mitral regurgitation and its relation to changes in
      echocardiographic indices of left ventricular function (systolic and diastolic
      dimensions, fractional shortening) and to changes in the 12 lead ECG; and the
      prevalence of mitral regurgitation in the anthracycline treated patients in
      comparison with previously studied normal volunteers of similar age. RESULTS: 34
      patients (11.6%) developed ultrasound detectable mitral regurgitation, which was
      not apparent clinically, during or after anthracycline treatment, compared with
      only 1.8% of a normal population of similar age (p < 0.0001). Nine of the 34 also
      developed non-specific T wave abnormalities. All 34 patients had normal systolic
      function at the time of initial detection of mitral regurgitation, but four later
      developed impaired left ventricular function (5, 11, 20, and 27 months after the
      first detection of mitral regurgitation). CONCLUSIONS: Mitral regurgitation
      occurs much more often in patients treated with anthracyclines than in the normal
      population. Echocardiographic detection of new mitral regurgitation with or
      without ECG abnormalities may be an early predictor of anthracycline
      cardiomyopathy.

PMID- 11250972
TI  - The echocardiographic diagnosis of totally anomalous pulmonary venous connection
      in the fetus.
AB  - BACKGROUND: Infants with isolated totally anomalous pulmonary venous return often
      present severely decompensated, such that they are at high risk for surgical
      repair. On the other hand, if surgical repair can be safely accomplished, the
      outlook is usually good. Thus prenatal diagnosis would be expected to improve the
      prognosis for the affected child. OBJECTIVE: To describe the features of isolated
      totally anomalous pulmonary venous drainage in the fetus. DESIGN: Four fetuses
      with isolated totally anomalous pulmonary venous connection were identified and
      the echocardiographic images reviewed. Measurements of the atrial and ventricular
      chambers and both great arteries were made and compared with normal values.
      SETTING: Referral centre for fetal echocardiography. RESULTS: There were two
      cases of drainage to the coronary sinus, one to the right superior vena cava, and
      one to the inferior vena cava. Right heart dilatation relative to left heart
      structures was a feature of two cases early on, and became evident in some ratios
      late in pregnancy in the remaining two. CONCLUSIONS: Ventricular and great
      arterial disproportion in the fetus can indicate a diagnosis of totally anomalous
      pulmonary venous connection above the diaphragm. However, in the presence of an
      atrial septal defect or with infradiaphragmatic drainage, right heart dilatation
      may not occur until late in pregnancy. The diagnosis of totally anomalous
      pulmonary venous drainage in fetal life can only be reliably excluded by direct
      examination of pulmonary venous blood flow entering the left atrium on colour or
      pulsed flow mapping.

PMID- 11250973
TI  - Survival with congenital heart disease and need for follow up in adult life.
AB  - OBJECTIVE: To predict the growth in demand for long term follow up of adults with
      congenital heart disease. DESIGN: Observed diagnoses of congenital heart disease
      in infancy and childhood were adjusted for observed infant survival, predicted
      further survival to age 16 years, underascertainment in older childhood, and
      predicted need for long term follow up. SETTING: The resident population of one
      health region in the UK. PATIENTS: All confirmed cardiovascular malformations
      diagnosed in 1985 to 1999 in children born in 1985 to 1994. RESULTS: 1942 cases
      of congenital heart disease were diagnosed in infancy in a population of 377 310
      live births (5.2/1000). 1588 (82%) survived to 1 year and 1514 were predicted to
      survive to age 16. 605 further diagnoses were made in childhood-678 when adjusted
      for underascertainment. Thus, 2192 children were predicted to reach age 16, of
      whom 784 would require long term follow up in adult life. The adult population
      would comprise 28% complex, 54% significant, and 18% minor congenital heart
      disease. These figures predict the need for adult follow up of congenital heart
      disease of over 200 extra cases per 100 000 live births each year or over 1600
      extra cases a year every year in the UK. CONCLUSIONS: The need for follow up of
      congenital heart disease in adult life is likely to grow linearly, with
      increasing complexity and increasing need for reinvestigation and reintervention
      with time. Appropriate provision should be made for adequate manpower, resources,
      and facilities for care of these patients.

PMID- 11250975
TI  - Assessment of the geometric profile of the Amplatzer and Cardioseal septal
      occluders by three dimensional echocardiography.
AB  - OBJECTIVE: To apply three dimensional echocardiography to describe the geometric
      profile of the Amplatzer and Cardioseal occluders after deployment for closure of
      atrial septal defect. METHODS: 20 patients (mean (SD) age, 14 (5) years) were
      enrolled for transcatheter closure of a secundum atrial septal defect with the
      Amplatzer occluder (10) or with the Cardioseal occluder (10). The two populations
      were matched for the stretched diameter of the defect (mean 18 (6) mm). The
      profile of the two occluders was examined. RESULTS: Transoesophageal
      echocardiography did not show any residual shunts after Amplatzer occluder
      deployment, whereas three patients had a small residual leak after Cardioseal
      deployment. One patient had transient atrioventricular block with the Amplatzer
      device. The mean surface area of the Amplatzer occluder was 6.9 (2) cm(2), and
      that of the Cardioseal device 5.4 (3) cm(2) (p = 0.03). The mean volume of the
      Amplatzer occluder was 9.2 (1) cm(3), while that of the Cardioseal occluder was
      3.5 (1) cm(3) (p < 0.0001). From the three dimensional views, the Cardioseal
      occluder looked like a flat square after deployment whereas the Amplatzer
      occluder took up a ball shape in the atrial cavity. CONCLUSIONS: Three
      dimensional views by multiplane transoesophageal echocardiography allow a
      realistic in vivo description of atrial septal occluders. The Amplatzer occluder,
      with its high geometric profile, allows complete closure of large atrial septal
      defects but with some risk of mechanical complications. Use of the Cardioseal
      device, with its small surface coverage and high residual shunt rate, should be
      limited to transcatheter closure of a patent foramen ovale or small atrial septal
      defects.

PMID- 11250974
TI  - Pharmacodynamics and safety of lefradafiban, an oral platelet glycoprotein
      IIb/IIIa receptor antagonist, in patients with stable coronary artery disease
      undergoing elective angioplasty.
AB  - OBJECTIVE: Lefradafiban is the orally active prodrug of fradafiban, a
      glycoprotein IIb/IIIa receptor antagonist. The present phase II study aimed to
      determine the dose of lefradafiban that provides 80% blockade of the glycoprotein
      IIb/IIIa receptors by fradafiban, and to study the pharmacodynamics and safety of
      different doses in patients with stable angina undergoing angioplasty. DESIGN: A
      double blind, placebo controlled, dose finding study. SETTING: Four academic and
      community hospitals in the Netherlands. PATIENTS: 64 patients with stable
      coronary artery disease undergoing elective percutaneous transluminal coronary
      angioplasty. INTERVENTIONS: 30 mg, 45 mg, and 60 mg of lefradafiban three times
      daily or placebo was given for 48 hours. MAIN OUTCOME MEASURES: The primary
      safety end point was the occurrence of bleeding, classified as major, minor, or
      insignificant according to the thrombolysis in myocardial infarction (TIMI)
      criteria. Efficacy indices included per cent fibrinogen receptor occupancy (FRO),
      ex vivo platelet aggregation, and plasma concentrations of fradafiban. RESULTS:
      Administration of lefradafiban 30, 45, and 60 mg three times daily resulted in a
      dose dependent increase in median FRO levels of 71%, 85%, and 88%, respectively.
      Inhibition of platelet aggregation was closely related to FRO. There were no
      major bleeding events. The 60 mg lefradafiban group had a high (71%) incidence of
      minor and insignificant bleeding. The incidence of bleeding was 44% in the 30 mg
      and 45 mg groups, compared with 9% in placebo patients. Puncture site bleeding
      was the most common event. The odds of bleeding increased by 3% for every 1%
      increase in FRO. CONCLUSIONS: Lefradafiban is an effective oral glycoprotein
      IIb/IIIa receptor blocker. The clinical effectiveness of doses up to 45 mg three
      times daily should be investigated.

PMID- 11250976
TI  - Effect of surgical training on outcome and hospital costs in coronary surgery.
AB  - BACKGROUND: There is a perceived conflict between the need for service provision
      and surgical training within the National Health Service (NHS). Trainee surgeons
      tend to be slower (thereby reducing theatre throughput), and may have more
      complications (increasing hospital stay and costs). OBJECTIVE: To quantify the
      effect of training on outcome and costs. DESIGN: Data on 2740 consecutive
      isolated coronary artery bypass (CABG) operations were analysed retrospectively.
      Redo and emergency procedures were excluded. The seniority of the operating
      surgeon was related to operating times, risk stratified outcome, and overall
      hospital costs. SETTING: Regional cardiothoracic surgery unit. MAIN OUTCOME
      MEASURES: Postoperative mortality; hospital costs. RESULTS: Consultants, senior
      trainees, intermediate trainees, and junior trainees performed 1524, 759, 434,
      and 23 procedures, respectively. Trainees at the three different levels were
      directly supervised by a consultant in 55%, 95%, and 100% of cases. The
      unadjusted mortalities were 3.2%, 2.0%, 2.3%, and 4.3%, respectively (NS). There
      were no significant differences between the groups with respect to time in the
      intensive care unit and length of hospital stay. The mean cost per patient was
      pound6619, pound6572, pound6494, and pound6404 (NS). CONCLUSIONS: Trainees
      performed 44.4% of all CABG operations. There was no detrimental effect on
      patient outcome, length of hospital stay, or overall hospital costs. There need
      be little conflict between service and training needs, even in hospitals with
      extensive training programmes.

PMID- 11250977
TI  - An unusual (subcarinal) case of pulmonary artery sling.

PMID- 11250979
TI  - Diabetic heart disease: clinical considerations.

PMID- 11250980
TI  - Endocarditis: problems--patients being treated for endocarditis and not doing
      well.

PMID- 11250978
TI  - Increased risk for ischaemic events is related to combined RAS polymorphism.
AB  - OBJECTIVE: To determine whether the angiotensin converting enzyme (ACE) and the
      angiotensin II type 1 receptor (AT(1)R A1166C) gene polymorphism interact to
      increase the risk of ischaemic events, and whether this can be explained by the
      progression of angiographically defined coronary atherosclerosis. DESIGN:
      Prospective defined substudy of the lipid lowering regression trial (REGRESS).
      SETTING: University hospital. PATIENTS: 885 male patients with stable coronary
      artery disease. MAIN OUTCOME MEASURES: Incidence of ischaemic events during a two
      year follow up; serial quantitative coronary arteriography (mean segment diameter
      and minimum obstruction diameter) at baseline and after two years. RESULTS:
      Patients who carried both the ACE-DD and AT(1)R-CC genotype had significantly
      more ischaemic events during the two year follow up than those carrying other
      genotype combinations (p = 0.035, Mantel-Haenszel test for linear association).
      There was no association between the two genotypes and mean segment diameter or
      minimum obstruction diameter at baseline or after two years. CONCLUSIONS: The
      suggestion that ACE-DD and AT(1)R-CC genotypes interact to increase the risk of
      ischaemic events is confirmed. However, this increased risk was not accompanied
      by increased progression of angiographically defined coronary atherosclerosis.

PMID- 11250981
TI  - Pulmonary arterial hypertension: new ideas and perspectives.

PMID- 11250982
TI  - Ultrasound guided percutaneous thrombin injection of iatrogenic femoral artery
      pseudoaneurysms after coronary angiography and intervention.
AB  - Ultrasound guided percutaneous thrombin injection has recently been described for
      the treatment of iatrogenic femoral pseudoaneurysms. Patient selection and
      technical aspects of this technique are still evolving and safety data,
      particularly after coronary intervention, remains limited. The percutaneous
      thrombin injection of femoral artery pseudoaneurysms in 13 consecutive patients,
      most of whom were receiving antiplatelet/anticoagulant treatment (aspirin 11,
      heparin 4, clopidogrel 6), is reported. Thrombin (1000 U/ml) was injected over
      several seconds until Doppler colour flow within the cavity ceased. The median
      dose of thrombin injected was 800 U (range 200-1000 U) and the treatment was
      successful in all cases without complication. In one case, thrombus was
      visualised within the arterial lumen immediately after thrombin injection, but
      this dissolved spontaneously within five minutes without evidence of
      embolisation. In contrast to ultrasound guided compression, percutaneous thrombin
      injection of femoral pseudoaneurysms is a rapid, well tolerated, and successful
      technique even in patients receiving antiplatelet/anticoagulant treatment.

PMID- 11250983
TI  - Spontaneous closure of congenital coronary artery fistulas.
AB  - Six cases of full spontaneous closure of congenital coronary artery fistulas, and
      one case of near closure, as seen by colour Doppler echocardiography, are
      presented. It is worth reconsidering the classical view that nearly all cases of
      spontaneous closure are eligible for surgical or percutaneous correction to
      prevent the development of significant and potentially fatal complications. As
      the natural course of coronary artery fistulas is still poorly defined,
      asymptomatic patients, especially those under 7 years old with small shunts,
      should be periodically followed up by echocardiography rather than be subjected
      to operative closure, even by catheterisation.

PMID- 11250984
TI  - Behcet's disease with a large intracardiac thrombus: a case report.
AB  - Behcet's disease is recognised as a chronic multisystem disorder with vasculitis
      as its underlying pathological process. Cardiac involvement is rare and often
      associated with poor prognosis. A case of a 33 year old man with Behcet's
      disease, presenting with a large right ventricle and right atrial thrombus, is
      reported. Two dimensional (cross sectional), colour Doppler, and transoesophageal
      echocardiography, angiography, computed tomography, and magnetic resonance
      imaging were used to diagnose the disease. With cyclophosphamide and
      dexamethasone treatment, the cardiac lesions progressively resolved.

PMID- 11250985
TI  - Serious adverse events experienced by patients with chronic heart failure taking
      spironolactone.
AB  - In patients with chronic heart failure, spironolactone added to conventional
      treatment may lead to serious and, occasionally, fatal hyperkalaemia. In some
      cases this seems to happen because spironolactone causes diarrhoea. Four cases
      involving men with New York Heart Association functional class III heart failure
      are presented. As these cases revealed, close monitoring of blood chemistry is
      mandatory after starting spironolactone, and patients should be advised to stop
      spironolactone immediately if diarrhoea develops.

PMID- 11250986
TI  - Prostate cancer: the price of early detection.

PMID- 11250987
TI  - Phase I/II study of the P-glycoprotein modulator PSC 833 in patients with acute
      myeloid leukemia.
AB  - PURPOSE: To determine the maximum-tolerated dose, pharmacokinetic interaction,
      and activity of PSC 833 compared with daunorubicin (DNR) and cytarabine in
      patients with poor-risk acute myeloid leukemia. PATIENTS AND METHODS: Patients
      received ara-C 3 g/m(2)/d on 5 consecutive days, followed by an IV loading dose
      of PSC 833 (1.5 mg/kg) and an 84-hour continuous infusion escalating from 6, 9,
      or 10 mg/kg/d. Daunorubicin was administered as a 72-hour continuous infusion at
      34 or 45 mg/m2/d [corrected]. Responding patients received consolidation
      chemotherapy with DNR pharmacokinetics performed without PSC-833 on day 1, and
      with PSC-833 on day 4. Response was correlated with expression of P-glycoprotein
      and lung resistance protein (LRP), and in vitro sensitization of leukemia
      progenitors to DNR cytotoxicity by PSC 833. RESULTS: All 43 patients are
      assessable for toxicity and response. Grade 3 or greater hyperbilirubinemia (70%)
      was the only dose-dependent toxicity. Four patients (9%) succumbed to treatment
      related complications. Twenty-one patients (49%) achieved a complete remission or
      restored chronic phase, including 10 of 20 patients treated at the maximum
      tolerated dose of 10 mg/kg/d of PSC-833 and 45 mg/m(2) of DNR. The 95% confidence
      interval for complete response was 33.9% to 63.7%. Administration of PSC 833 did
      not alter the mean area under the curve for DNR, although clearance decreased
      approximately two-fold (P =.04). Daunorubicinol clearance decreased 3.3-fold (P
      =.016). Remission rates were not effected by mdr-1 expression, but LRP
      overexpression was associated with chemotherapy resistance. CONCLUSION: Combined
      treatment with infused PSC 833 and DNR is well tolerated and has activity in
      patients with poor risk acute myeloid leukemia. Administration of PSC 833 delays
      elimination of daunorubicinol, but yields variable changes in DNR systemic
      exposure.

PMID- 11250988
TI  - Long-term persistence of monoclonal B cells after cure of Helicobacter pylori
      infection and complete histologic remission in gastric mucosa-associated lymphoid
      tissue B-cell lymphoma.
AB  - PURPOSE: Cure of Helicobacter pylori infection is associated with remission
      induction in the majority of patients with low-grade gastric mucosa associated
      lymphoid tissue (MALT) lymphoma in localized stages; however, limited data exist
      as to whether these patients may be cured of their lymphoma. The present study
      was performed to investigate whether the polymerase chain reaction (PCR) for the
      rearranged immunoglobulin heavy chain region may be used to define "molecular"
      remission. PATIENTS AND METHODS: Ninety-seven patients who suffered from low
      grade gastric MALT lymphoma stage I(E) were observed with central pathology and
      molecular biology after cure of H pylori infection. PCR was performed with the
      use of consensus primers for the framework regions 1, 2, and 3 and monoclonality
      was corroborated by sequence analysis. In selected cases, microdissection was
      performed to study the origin of the monoclonal B cells. RESULTS: Of the 97
      patients, 77 obtained complete endoscopic and histologic remission (CR). Twenty
      of 44 patients with PCR monoclonality at diagnosis and with sufficient molecular
      follow-up displayed monoclonal bands for a median time of 20.5 months after CR
      (range, 0 to 50.4 months). These B cells were related to the original lymphoma
      clone by sequence analysis. Microdissection analysis identified basal lymphoid
      aggregates as the source of these monoclonal B cells. Local relapse occurred in
      and was observed by PCR in four patients. All four patients displayed monoclonal
      PCR before relapse, and three of these four showed ongoing PCR monoclonality
      throughout their course, indicating the persistence of malignant cells.
      CONCLUSION: Half of all patients with gastric MALT lymphoma show long-term PCR
      monoclonality up to several years after cure of H pylori infection and CR.
      Patients with monoclonal PCR should be observed closely, whereas long-term PCR
      negativity may indicate cure of the disease.

PMID- 11250989
TI  - Lung cancer after Hodgkin's disease: a nested case-control study of the relation
      to treatment.
AB  - PURPOSE: To investigate the causes of the raised risk of lung cancer in patients
      who have had Hodgkin's disease, and in particular the relationship to treatment.
      PATIENTS AND METHODS: A nested case-control study was conducted within a cohort
      of 5,519 patients with Hodgkin's disease treated in Britain during 1963 through
      1993. For 88 cases of lung cancer and 176 matched control subjects, information
      on treatment and other risk factors was extracted from hospital case-notes, and
      odds ratios for lung cancer in relation to these factors were calculated.
      RESULTS: Risk of lung cancer was borderline significantly greater in patients
      treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)
      chemotherapy than those who did not receive this treatment (relative risk [RR] =
      1.66; 95% confidence interval [CI], 0.99 to 2.82), and increased with number of
      cycles of MOPP (P =.07). Exclusion of lung cancers for which histologic
      confirmation was not available strengthened these associations (RR = 2.41; 95%
      CI, 1.33 to 4.51; P =.004 for any MOPP and P =.007 for trend with number of
      cycles of MOPP). Risks were not raised, however, after chlorambucil, vinblastine,
      procarbazine, and prednisone treatment. There was evidence that the raised risk
      of lung cancer occurring in relation to radiotherapy was restricted to
      histologies other than adenocarcinoma. CONCLUSION: The results suggest that MOPP
      chemotherapy may lead to elevated risk of lung cancer, at least in certain
      subgroups of patients. The role of chemotherapy in the etiology of lung cancer
      after Hodgkin's disease deserves further investigation.

PMID- 11250990
TI  - Health-related quality-of-life effects of radical prostatectomy and primary
      radiotherapy for screen-detected or clinically diagnosed localized prostate
      cancer.
AB  - PURPOSE: The current study was undertaken within the framework of a screening
      trial to compare the health-related quality-of-life (HRQOL) outcomes of two
      primary treatment modalities for localized prostate cancer: radical prostatectomy
      and external-beam radiotherapy. PATIENTS AND METHODS: We conducted a prospective
      longitudinal cohort study among 278 patients with early screen-detected (59%) or
      clinically diagnosed (41%) prostate cancer using both generic and disease
      specific HRQOL measures (SF-36, UCLA Prostate Cancer Index [urinary and bowel
      modules] and items relating to sexual functioning) at three points in time: t1
      (baseline), t2 (6 months later), and t3 (12 months after t1). RESULTS:
      Questionnaires were completed by 88% to 93% of all initially enrolled patients.
      Patients referred for primary radiotherapy were significantly older than
      prostatectomy patients (63 v 68 years, P <.01). Analyses (adjusted for age and
      pretreatment level of functioning) revealed poorer levels of generic HRQOL after
      radiotherapy. Prostatectomy patients reported significantly higher (P <.01)
      posttreatment incidences of urinary incontinence (39% to 49%) and erectile
      dysfunction (80% to 91%) than radiotherapy patients (respectively, 6% to 7% and
      41% to 55%). Bowel problems (urgency) affected 30% to 35% of the radiotherapy
      group versus 6% to 7% of the prostatectomy group (P <.01). Patients with screen
      detected and clinically diagnosed cancer reported similar posttreatment HRQOL.
      CONCLUSION: Prostatectomy and radiotherapy differed in the type of HRQOL
      impairment. Because the HRQOL effects may be valued differently at the individual
      level, patients should be made fully aware of the potential benefits and adverse
      consequences of therapies for early prostate cancer. Differences in posttreatment
      HRQOL were not related to the method of cancer detection.

PMID- 11250991
TI  - Equivalence of three or four cycles of bleomycin, etoposide, and cisplatin
      chemotherapy and of a 3- or 5-day schedule in good-prognosis germ cell cancer: a
      randomized study of the European Organization for Research and Treatment of
      Cancer Genitourinary Tract Cancer Cooperative Group and the Medical Research
      Council.
AB  - PURPOSE: To test the equivalence of three versus four cycles of bleomycin,
      etoposide, and cisplatin (BEP) and of the 5-day schedule versus 3 days per cycle
      in good-prognosis germ cell cancer. PATIENTS AND METHODS: The study was designed
      as a 2 x 2 factorial trial. The aim was to rule out a 5% decrease in the 2-year
      progression-free survival (PFS) rate. The study included the assessment of
      patient quality of life. A cycle of BEP consisted of etoposide 500 mg/m(2),
      administered at either 100 mg/m(2) days 1 through 5 or 165 mg/m(2) days 1 through
      3, cisplatin 100 mg/m(2), administered at either 20 mg/m(2) days 1 through 5 or
      50 mg/m(2) days 1 and 2. Bleomycin 30 mg was administered on days 1, 8, and 15
      during cycles 1 through 3. The randomization procedure allowed some investigators
      to participate only in the comparison of three versus four cycles. RESULTS: From
      March 1995 until April 1998, 812 patients were randomly assigned to receive three
      or four cycles: of these, 681 were also randomly assigned to the 5-day or the 3
      day schedule. Histology, marker values, and disease extent are well balanced in
      the treatment arms of the two comparisons. The projected 2-year PFS is 90.4% on
      three cycles and 89.4% on four cycles. The difference in PFS between three and
      four cycles is -1.0% (80% confidence limit [CL], -3.8%, +1.8%). Equivalence for
      three versus four cycles is claimed because both the upper and lower bounds of
      the 80% CL are less than 5%. In the 5- versus 3-day comparison, the projected 2
      year PFS is 88.8% and 89.7%, respectively (difference, -0.9%, (80% CL, -4.1%,
      +2.2%). Hence, equivalence is claimed in this comparison also. Frequencies of
      hematologic and nonhematologic toxicities were essentially similar. Quality of
      life was maintained better in patients receiving three cycles; no differences
      were detected between 3 and 5 days of treatment. CONCLUSION: We conclude that
      three cycles of BEP, with etoposide at 500 mg/m(2), is sufficient therapy in good
      prognosis germ cell cancer and that the administration of the chemotherapy in 3
      days has no detrimental effect on the effectiveness of the BEP regimen.

PMID- 11250993
TI  - Improved prognostication of renal cell carcinoma using an integrated staging
      system.
AB  - PURPOSE: To integrate stage, grade, and Eastern Cooperative Oncology Group (ECOG)
      performance status (PS) into a clinically useful tool capable of stratifying the
      survival of renal cell carcinoma (RCC) patients. PATIENTS AND METHODS: The
      medical records of 661 patients undergoing nephrectomy at University of
      California Los Angeles between 1989 and 1999 were evaluated. Median age was 61
      years, male-to-female ratio was 2.2:1, and median follow-up was 37 months.
      Survival time was the primary end point assessed. Sixty-four possible
      combinations of stage, grade, and ECOG PS were analyzed and collapsed into
      distinct groups. The internal validity of the categorized was challenged by a
      univariate analysis and a multivariate analysis testing for the accountability of
      each UCLA Integrated Staging System (UISS) category against independent variables
      shown to have impact on survival. RESULTS: Combining and stratifying 1997 tumor
      node-metastasis stage, Fuhrman's grade and ECOG PS resulted in five survival
      stratification groups designated UISS, and numbered I to V. The projected 2- and
      5-year survival for the UISS groups are as follows for the groups: I, 96% and
      94%; II, 89% and 67%; III, 66% and 39%; IV, 42% and 23%; and V, 9% and 0%,
      respectively. UISS accounted for the significant variables in the variate
      analysis. CONCLUSION: A novel system for staging and predicting survival for RCC
      integrating clinical variables is offered. UISS is simple to use and is superior
      to stage alone in differentiating patients' survival. Our data suggests that UISS
      is an important prognostic tool for counseling patients with various stages of
      kidney cancer. Further prospective large-scale validation with external data is
      awaited.

PMID- 11250992
TI  - Second-line chemotherapy in patients with relapsed extragonadal nonseminomatous
      germ cell tumors: results of an international multicenter analysis.
AB  - PURPOSE: Relapsed extragonadal germ cell tumors patients (EGGCT) are treated with
      identical salvage chemotherapy regimens, as are patients with metastatic
      testicular cancer. This investigation evaluates the results of second-line
      chemotherapy in nonseminomatous EGGCT and tries to identify prognostic factors
      for survival. PATIENTS AND METHODS: We conducted a retrospective review of 142
      patients treated at eleven European and American centers between 1975 and 1996.
      All had received cisplatin-containing regimens as induction treatment. RESULTS:
      Twenty-seven of 142 patients (19%) were long-term disease-free, 11% with primary
      mediastinal and 30% of patients with primary retroperitoneal disease. Median
      follow-up since start of salvage treatment was 11 months (range, 1 to 157) for
      all patients and 45 months (range, 6 to 157) for surviving patients. Forty-eight
      patients (34%) received high dose chemotherapy with autologous bone marrow
      transplant at relapse, and 10 of these patients (21%) are continuously disease
      free. Primary mediastinal location (P =.003), sensitivity to cisplatin (P =.003),
      elevated beta-HCG at relapse (P: =.04), and normal LDH at diagnosis (P =.01) were
      shown to be significant negative prognostic factors for overall survival in
      univariate; mediastinal location [relative risk ratios (HR) = 1.9; 95% confidence
      intervals (CI), 1.2 to 3.0] and sensitivity to cisplatin [HR = 2.4; 95% CI, 1.1
      to 5.2] were significant negative prognostic factors in multivariate analysis.
      CONCLUSION: Although current salvage strategies will cure between 20% and 50% of
      recurrent metastatic testicular cancer, relapsed nonseminomatous EGGCT patients
      appear to have an inferior survival rate, in particular in case of primary
      mediastinal location. Mediastinal primary tumor and inadequate response to
      cisplatin-based induction chemotherapy have been identified as independent
      negative prognostic factors, both associated with an approximately two-fold
      higher risk for failure of salvage treatment.

PMID- 11250994
TI  - Recommendations for cancer prevention trials using potentially ototoxic test
      agents.
AB  - PURPOSE: Preventive oncology applies pharmacologic agents to reverse, retard, or
      halt progression of neoplastic cells to invasive malignancy, a process that may
      require administration of agents over long periods of time. Although ototoxicity
      may be a tolerable side effect of anticancer or antimicrobial therapy, even
      modest ototoxicity may not be acceptable in agents developed for preventive
      oncology that are routinely administered to subjects who neither are, nor
      necessarily will become, clinically ill. MATERIALS AND METHODS: Age-related
      shifts in hearing may occur over the course of longterm or open-ended therapy;
      consequently, age-adjusted norms enable researchers to better distinguish hearing
      loss caused by drugs from that caused by aging. Norms for hearing sensitivity are
      derived from the Baltimore Longitudinal Study of Aging and are the basis for the
      proposed audiologic monitoring recommendations. RESULTS: Audiologic monitoring
      recommendations are presented that standardize patient selection, adverse event
      reporting, posttreatment follow-up, and audiologic testing for potentially
      ototoxic investigational agents. CONCLUSION: These recommendations are applicable
      to trials of investigational agents as well as various classes of drugs used in
      routine clinical care.

PMID- 11250995
TI  - Safety of the synthetic retinoid fenretinide: long-term results from a controlled
      clinical trial for the prevention of contralateral breast cancer.
AB  - PURPOSE: To describe the pattern of occurrence of adverse events commonly arising
      during treatment with fenretinide, a synthetic retinoid under investigation for
      cancer prevention. PATIENTS AND METHODS: The series includes 2,867 women accrued
      in a trial aimed at assessing the effect of fenretinide on the prevention of
      second breast malignancy. Women were randomly assigned to receive no treatment
      (1,435 patients) or 5-year fenretinide treatment (1,432 patients). In terms of
      disease recurrence in the breast, the trial showed a possible beneficial effect
      of the compound in premenopausal women, and an opposite trend in postmenopausal
      women. End points considered for safety assessment were the occurrence of
      diminished dark adaptation, dermatologic disorders, gastrointestinal symptoms,
      disorders of the ocular surface, and abnormal laboratory values. RESULTS: The
      most common adverse events were diminished dark adaptation (cumulative incidence,
      19.0%) and dermatologic disorders (18.6%). Less common events were
      gastrointestinal symptoms (13.0%) and disorders of the ocular surface (10.9%). In
      comparison, incidence figures in the control arm were 2.9% for diminished dark
      adaptation, 2.9% for dermatologic disorders, 5.4% for gastrointestinal symptoms,
      and 3.2% for disorders of the ocular surface. Symptoms occurring during
      fenretinide treatment tended to recover with time. No between-group difference
      was observed for the occurrence of laboratory data abnormalities. Overall, 63
      (4.4%) treatment discontinuations were caused by adverse events. CONCLUSION:
      Given the number of patients involved in the study and the prolonged intake of
      the drug, the experience on fenretinide tolerability can be considered
      sufficiently reassuring to justify further testing of the retinoid.

PMID- 11250996
TI  - Effect of pregnancy on overall survival after the diagnosis of early-stage breast
      cancer.
AB  - PURPOSE: To evaluate the impact of subsequent pregnancy on the prognosis of
      patients with early breast cancer. PATIENTS AND METHODS: One hundred eight
      patients who became pregnant after diagnosis of early-stage breast cancer were
      identified in institutions participating in International Breast Cancer Study
      Group (IBCSG) studies. Fourteen had relapse of breast cancer before their first
      subsequent pregnancy. The remaining 94 patients (including eight who relapsed
      during pregnancy) formed the study group reported here. A comparison group of 188
      was obtained by randomly selecting two patients, matched for nodal status, tumor
      size, age, and year of diagnosis from the IBCSG database, who were free of
      relapse for at least as long as the time between breast cancer diagnosis and
      completion of pregnancy for each pregnant patient. Survival comparison used Cox
      proportional hazards regression models. RESULTS: Overall 5- and 10-year survival
      percentages (+/- SE) measured from the diagnosis of early-stage breast cancer
      among the 94 study group patients were 92% +/- 3% and 86% +/- 4%, respectively.
      For the matched comparison group survival was 85% +/- 3% at 5 years and 74% +/-
      4% at 10 years (risk ratio, 0.44; 95% confidence interval, 0.21 to 0.96; P =.04).
      CONCLUSION: Subsequent pregnancy does not adversely affect the prognosis of early
      stage breast cancer. The superior survival seen in this and other controlled
      series may merely reflect a healthy patient selection bias, but is also
      consistent with an antitumor effect of the pregnancy.

PMID- 11250997
TI  - Decision support for patients with early-stage breast cancer: effects of an
      interactive breast cancer CDROM on treatment decision, satisfaction, and quality
      of life.
AB  - PURPOSE: To investigate the effects of the Interactive Breast Cancer CDROM as a
      decision aid for breast cancer patients with a choice between breast conserving
      therapy (BCT) and mastectomy (MT). PATIENTS AND METHODS: Consecutive patients
      with stage I and II breast cancer were enrolled. A quasi-experimental,
      longitudinal, and pretest/posttest design was used. Follow-up was scheduled 3 and
      9 months after discharge from the hospital. Control patients (n = 88) received
      standard care (oral information and brochures). The CDROM was provided to
      patients in the experimental condition (n = 92) as a supplement to standard
      procedures. Outcome variables were treatment decision, satisfaction, and quality
      of life (QoL). RESULTS: No effect on treatment decision was found. CDROM patients
      expressed more general satisfaction with information at 3 and 9 months (95%
      confidence interval for the difference (d) between the means (d: 4.1 to 12.5 and
      5.7 to 14.2 respectively). CDROM patients were also more satisfied with their
      treatment decision at 3 and at 9 months (d: 0.1 to 0.4; 0.2 to 0.5). Moreover, at
      9 months, CDROM patients were more satisfied with breast cancer-specific
      information (d: 0.9 to 16.5), the decision-making process (d: 0.1 to 0.4), and
      communication (d: 0.2 to 11.0). At 3 and 9 months, a positive effect was found on
      general health (d: 0.2 to 14.5 and 0.3 to 15.0). Moreover, at 9 months, CDROM
      patients reported better physical functioning (d: 5.1 to 19.8), less pain (d: 
      17.9 to -4.5), and fewer arm symptoms (d: -14.1 to -0.5). CONCLUSION: The
      Interactive Breast Cancer CDROM improved decision making in patients with early
      stage breast cancer with a choice between BCT and MT, as evaluated in terms of
      patients' satisfaction and QoL.

PMID- 11250998
TI  - Differences in risk factors for local and distant recurrence after breast
      conserving therapy or mastectomy for stage I and II breast cancer: pooled results
      of two large European randomized trials.
AB  - PURPOSE: Risk factors for local and distant recurrence after breast-conserving
      therapy and mastectomy were compared to define guidelines for the decision making
      between both treatments. PATIENTS AND METHODS: The data of two randomized
      clinical trials for stage I and II breast cancer patients were pooled. The total
      number of patients in the study was 1,772, of whom 879 underwent breast
      conservation, and 893, modified radical mastectomy. Representative slides of the
      primary tumor were available for histopathologic review in 1,610 cases (91%).
      RESULTS: There were 79 patients with local recurrence after breast-conservation
      and 80 after mastectomy, the 10-year rates being 10% (95% confidence interval
      [CI], 8% to 13%) and 9% (95% CI, 7% to 12%), respectively. Age no more than 35
      years (compared with age >60: hazard ratio [HR], 9.24; 95% CI, 3.74 to 22.81) and
      an extensive intraductal component (HR, 2.52; 95% CI, 1.26 to 5.00) were
      significantly associated with an increased risk of local recurrence after breast
      conserving therapy. Vascular invasion was predictive of the risk of local
      recurrence, irrespective of the type of primary treatment (P <.01). Tumor size,
      nodal status, high histologic grade, and vascular invasion were all highly
      significant predictors of distant disease after breast-conserving therapy and
      mastectomy (P <.01). Age no more than 35 years and microscopic involvement of the
      excision margin were additional independent predictors of distant disease after
      breast-conserving therapy (P <.01). CONCLUSION: Age no more than 35 years and the
      presence of an extensive intraductal component are associated with an increased
      risk of local recurrence after breast-conserving therapy. Vascular invasion
      causes a higher risk of local recurrence after mastectomy as well as after breast
      conserving therapy and should therefore not be used for deciding between the two
      treatments.

PMID- 11250999
TI  - Comparison of methods of measuring HER-2 in metastatic breast cancer patients
      treated with high-dose chemotherapy.
AB  - PURPOSE: HER-2 is overexpressed in 20% to 30% of human breast cancer and is
      associated with poor outcome. Studies suggest an association between HER-2
      overexpression and resistance to alkylating agents. To further evaluate this
      relationship, we assessed the interaction of HER-2, measured by different
      methods, and outcome after dose intensification with alkylating agents in
      metastatic breast cancer. PATIENTS AND METHODS: From 1988 to 1995 at Duke
      University, 425 patients with metastatic breast cancer were enrolled in a study
      of high-dose alkylating agents (HDC) with autologous cellular support after
      doxorubicin-based therapy (AFM). HER-2 was measured in serum for shed
      extracellular domain (ECD) and in tissue by immunohistochemistry (IHC) and
      fluorescent in situ hybridization (FISH). RESULTS: HER-2 ECD was positive in 29%
      (19 of 65) of patients pre-AFM and in 11.7% (34 of 290) pre-HDC. Higher pre-AFM
      and higher pre-HDC HER-2 ECD predicted worse overall survival (P =.045 and P
      =.0096, respectively). HER-2 overexpression by IHC and FISH showed no correlation
      with worse disease-free survival or overall survival. FISH and ECD were highly
      specific for IHC (97.3% and 97.7% respectively). However, ECD had a low
      sensitivity for IHC-only 22% of patients with HER-2 in the primary tumor shed ECD
      into the serum. CONCLUSION: These data suggest that the method of measuring HER-2
      is important in predicting clinical outcome. HER2 ECD may identify a poor
      prognosis subgroup of HER-2-positive tumors. Lack of association of HER2 by
      IHC/FISH with worse outcome suggests that therapy with AFM and/or HDC therapy may
      be able to overcome the effect of this prognostic factor or it may not be a
      prognostic factor in this setting.

PMID- 11251000
TI  - Doxorubicin and paclitaxel versus fluorouracil, doxorubicin, and cyclophosphamide
      as first-line therapy for women with metastatic breast cancer: final results of a
      randomized phase III multicenter trial.
AB  - PURPOSE: This phase III trial compared the efficacy and safety of doxorubicin and
      paclitaxel (AT) to 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) as
      first-line therapy for women with metastatic breast cancer. PATIENTS AND METHODS:
      A total of 267 women with metastatic breast cancer were randomized to receive
      either AT (doxorubicin 50 mg/m(2) followed 24 hours later by paclitaxel 220
      mg/m(2)) or FAC (5-fluorouracil 500 mg/m(2), doxorubicin 50 mg/m(2),
      cyclophosphamide 500 mg/m(2)), each administered every 3 weeks for up to eight
      cycles. Patients had to have measurable disease and an Eastern Cooperative
      Oncology Group performance status of 0 to 2. Only one prior non-anthracycline,
      nontaxane-containing adjuvant chemotherapy regimen was allowed. RESULTS: Overall
      response rates for patients randomized to AT and FAC were 68% and 55%,
      respectively (P =.032). Median time to progression and overall survival were
      significantly longer for AT compared with FAC (time to progression 8.3 months v
      6.2 months [P =.034]; overall survival 23.3 months v 18.3 months [P =.013]).
      Therapy was generally well-tolerated (median of eight cycles delivered in each
      arm). Grade 3 or 4 neutropenia was more common with AT than with FAC (89% v 65%;
      P <.001); however, the incidence of fever and infection was low. Grade 3 or 4
      arthralgia and myalgia, peripheral neuropathy, and diarrhea were more common with
      AT, whereas nausea and vomiting were more common with FAC. The incidence of
      cardiotoxicity was low in both arms. CONCLUSION: AT conferred a significant
      advantage in response rate, time to progression, and overall survival compared
      with FAC. Treatment was well-tolerated with no unexpected toxicities.

PMID- 11251001
TI  - Phase I study of stealth liposomal doxorubicin in combination with gemcitabine in
      the treatment of patients with metastatic breast cancer.
AB  - PURPOSE: We conducted a single-institution phase I clinical trial to determine
      the maximum-tolerated dose (MTD) and define the toxic effects of stealth
      liposomal doxorubicin in combination with gemcitabine in patients with metastatic
      breast cancer. PATIENTS AND METHODS: Patients were eligible if they had disease
      progression with no limit on prior number of chemotherapy regimens. Prior
      treatment with liposomal doxorubicin and/or gemcitabine was not allowed. The
      starting dose of liposomal doxorubicin was 20 mg/m(2) on day 1 only with a 20%
      dose escalation of the previous mg/m(2) dose until MTD was reached. Gemcitabine
      was given as a fixed dose of 800 mg/m(2) on days 1 and 8 every 3 weeks. RESULTS:
      We treated 27 patients of whom six had never received chemotherapy for their
      disease. Most had had visceral involvement as their dominant site of disease. The
      dose-limiting toxicity was myelosuppression, which included neutropenia and
      thrombocytopenia. However, neither neutropenic fever nor episodes of bleeding
      were major occurrences. Significant antitumor activity was also observed with a
      total of two complete and seven partial responses. The recommended phase II dose
      is liposomal doxorubicin 24 mg/m(2) on day 1 and gemcitabine 800 mg/m(2) on days
      1 and 8 every 21 days. CONCLUSION: The combination of liposomal doxorubicin and
      gemcitabine is an active and well tolerated regimen when administered on a 21-day
      schedule. Myelosuppression limited further dose escalation, however, it did not
      increase the incidence of neutropenic fever. Significant antitumor activity seen
      in heavily and minimally pretreated patients warrants further evaluation of this
      combination.

PMID- 11251002
TI  - Interlaboratory evaluation of a new reverse transcriptase polymerase chain
      reaction-based enzyme-linked immunosorbent assay for the detection of circulating
      melanoma cells: a multicenter study of the Dermatologic Cooperative Oncology
      Group.
AB  - PURPOSE: Reverse transcription-polymerase chain reaction (RT-PCR)-based detection
      of tyrosinase mRNA is the most frequently used laboratory method for the
      detection of circulating tumor cells in melanoma patients. However, previously
      published results showed considerable variability in the PCR positivity rates.
      MATERIALS AND METHODS: We designed a collaborative study to assess the
      sensitivity, specificity, and clinical relevance of a new standardized RT-PCR
      based enzyme-linked immunosorbent assay (ELISA) for the detection of circulating
      melanoma cells. Blood samples of healthy donors mixed with cells of a melanoma
      cell line were prepared in a blinded fashion, and aliquots were sent to seven
      participating laboratories experienced in RT-PCR. RESULTS: The results
      demonstrate a high sensitivity (1 melanoma cell/mL blood) and specificity (no
      false-negatives and 7.4% [2 of 28] false-positives) of the assay and a
      satisfactory rate of interlaboratory reproducibility. The analysis of aliquots of
      blinded samples derived from 60 melanoma patients identified tyrosinase mRNA in
      17 of 60 (28.3%): three (20%) of 15 stage I patients, two (13.3%) of 15 stage II
      patients, five (35.7%) of 14 stage III patients, and seven (43.8%) of 16 stage IV
      patients. The interlaboratory reproducibility of positive samples, however, was
      extremely low and indicates the presence of low amounts of target mRNA.
      CONCLUSION: Reverse transcriptase-PCR ELISA has a high sensitivity and
      specificity for the detection of tyrosinase mRNA in peripheral blood cells. The
      low interlaboratory reproducibility for the detection of tumor cells in blood
      samples of melanoma patients, however, raises the question of relevance of this
      assay for clinical use.

PMID- 11251003
TI  - Prospective evaluation of cancer clinical trial accrual patterns: identifying
      potential barriers to enrollment.
AB  - PURPOSE: Well-conducted cancer clinical trials are essential for improving
      patient outcomes. Unfortunately, only 3% of new cancer patients participate in
      clinical trials. Barriers to patient accrual in cancer clinical trials must be
      identified and overcome to increase patient participation. MATERIALS AND METHODS:
      We prospectively tracked factors that potentially affected patient accrual into
      cancer clinical trials at the University of California Davis Cancer Center.
      Oncologists seeing new outpatients were asked to complete questionnaires
      regarding patient characteristics and the physician's decision-making on patient
      eligibility, protocol availability, and patient opinions on participation.
      Statistical analysis was performed to correlate these parameters with subsequent
      protocol accrual. RESULTS: There were 276 assessable patients. At the initial
      visits, physicians did not consider clinical trials in 38% (105/276) of patients
      principally because of a perception of protocol unavailability and poor
      performance status. Physicians considered 62% (171/276) of patients for
      participation in clinical trials. Of these, only 53% (91/171) had an appropriate
      protocol available for site and stage of disease. Seventy-six of 90 patients
      (84%) with available protocols met eligibility criteria for a particular study.
      Only 39 of 76 patients (51%) agreed to participate in cancer clinical trials, for
      an overall accrual rate of 14% (39/276). The remainder (37/76, 49%) declined
      trial participation despite meeting eligibility criteria. The most common reasons
      were a desire for other treatment (34%), distance from the cancer center (13%),
      patient refusal to disclose reason (11%), and insurance denial (8%). Patients
      with private insurance were less likely to enroll in clinical trials compared to
      those with government-funded insurance (OR, 0.34; P =.03; 95% CI, 0.13 to 0.9).
      CONCLUSION: Barriers to cancer clinical trial accrual can be prospectively
      identified and addressed in the development and conduct of future studies, which
      may potentially lead to more robust clinical trials enrollment. Investigation of
      patient perceptions regarding the clinical trials process and the role of third
      party-payers is warranted.

PMID- 11251004
TI  - Twenty-two years of phase III trials for patients with advanced non-small-cell
      lung cancer: sobering results.
AB  - PURPOSE: To determine the changes in clinical trials and outcomes of patients
      with advanced-stage non-small-cell lung cancer (NSCLC) treated on phase III
      randomized trials initiated in North America from 1973 to 1994. PATIENTS AND
      METHODS: Phase III trials for patients with advanced-stage NSCLC were identified
      through a search of the National Cancer Institute's Cancer Therapy Evaluation
      Program database from 1973 to 1994, contact with Cooperative Groups, and by
      literature search of MEDLINE. Patients with advanced NSCLC treated during a
      similar time interval were also examined in the SEER database. Trends were tested
      in the number of trials, in the number and sex of patients entered on the trials,
      and in survival over time. RESULTS: Thirty-three phase III trials were initiated
      between 1973 and 1994. Twenty-four trials (73%) were initiated within the first
      half of this period (1973 to 1983) and accounted for 5,359 (64%) of the 8,434
      eligible patients. The median number of patients treated per arm of the trials
      rose from 77 (1973 to 1983) to 121 (1984 to 1994) (P <.001). Five trials (15%)
      showed a statistically significant difference in survival between treatment arms,
      with a median prolongation of the median survival of 2 months (range, 0.7 to 2.7
      months). CONCLUSION: Analysis of past trials in North America shows that the
      prolongation in median survival between two arms of a randomized study was rarely
      in excess of 2 months. Techniques for improved use of patient resources and
      appropriate trial design for phase III randomized therapeutic trials with
      patients with advanced NSCLC need to be developed.

PMID- 11251005
TI  - Phase ii comparator study of oral versus intravenous topotecan in patients with
      chemosensitive small-cell lung cancer.
AB  - PURPOSE: Topotecan, administered intravenously, is active in small-cell lung
      cancer (SCLC). In this study, the comparability of oral topotecan to IV topotecan
      was investigated. PATIENTS AND METHODS: Patients with SCLC that had relapsed 90
      days or more after cessation of initial chemotherapy were randomized to receive
      either oral topotecan (Hycamtin) 2.3 mg/m(2)/d x 5 (52 patients) or IV topotecan
      1.5 mg/m(2)/d x 5 (54 patients), every 21 days. RESULTS: Response rates in this
      phase II randomized study were 23% (12/52) in the oral topotecan arm and 15%
      (8/54) in the IV topotecan arm. All radiological responses were confirmed by an
      independent radiologist. Median survival was 32 weeks (oral) and 25 weeks (IV).
      Good symptom control, defined as sustained improvement or no deterioration, was
      evident in both treatment groups. Topotecan was generally well tolerated, with
      myelosuppression being the major toxicity. Grade 4 neutropenia occurred in 35.3%
      of patients on oral topotecan and in 67.3% of patients on IV topotecan, which was
      statistically significant (P =.001). Fever/infection more than or equal to grade
      2 associated with grade 4 neutropenia, together with sepsis, occurred in only
      5.1% of courses (oral) and 3.3% of courses (IV). Non-hematological toxicity
      consisted mainly of vomiting (oral: 36.5% of patients; IV: 31.5% of patients) and
      nausea (oral: 26.9% of patients; IV: 40.7% of patients). CONCLUSION: This study
      found oral topotecan to be similar in efficacy to IV topotecan in the treatment
      of patients with relapsed SCLC, sensitive to first-line chemotherapy, with less
      grade 4 neutropenia and greater convenience of administration.

PMID- 11251006
TI  - Adenovirus-mediated wild-type p53 gene transfer in patients receiving
      chemotherapy for advanced non-small-cell lung cancer: results of a multicenter
      phase II study.
AB  - PURPOSE: To study the additional benefit from adenoviral p53 gene therapy in
      patients undergoing first-line chemotherapy for advanced non-small-cell lung
      cancer (NSCLC). PATIENTS AND METHODS: Twenty-five patients with nonresectable
      NSCLC were enrolled in an open-label, multicenter phase II study of three cycles
      of regimen A, carboplatin (area under the curve, 6; day 1) plus paclitaxel (175
      mg/m(2), day 1), or regimen B, cisplatin (100 mg/m(2), day 1) plus vinorelbine
      (25 mg/m(2), days 1, 8, 15, and 22) in combination with intratumoral injection of
      7.5 x 10(12) particles of SCH 58500 (rAd/p53, day 1). Responses of individual
      tumor lesions were assessed after each cycle, and gene transfer was examined in
      posttreatment tumor biopsies using reverse transcriptase polymerase chain
      reaction. RESULTS: There was no difference between the response rate of lesions
      treated with p53 gene therapy in addition to chemotherapy (52% objective
      responses) and lesions treated with chemotherapy alone (48% objective responses).
      Subgroup analysis according to the chemotherapy regimens revealed evidence for
      increased mean local tumor regressions in response to additional p53 gene therapy
      in patients receiving regimen B, but not in patients receiving regimen A. There
      was no survival difference between the two chemotherapy regimens, and the median
      survival of the cohort was 10.5 months (1-year survival, 44%). Transgene
      expression was confirmed in tumor samples from 68% of patients, and toxicities
      attributable to gene therapy were mild to moderate. CONCLUSION: Intratumoral
      adenoviral p53 gene therapy appears to provide no additional benefit in patients
      receiving an effective first-line chemotherapy for advanced NSCLC.

PMID- 11251007
TI  - Prevention of cisplatin-induced emesis by the oral neurokinin-1 antagonist, MK
      869, in combination with granisetron and dexamethasone or with dexamethasone
      alone.
AB  - PURPOSE: The NK1-receptor antagonist MK-869 (L-754,030) has demonstrated
      antiemetic activity in humans receiving chemotherapy. Objectives of the present
      trial included the first assessment of oral MK-869 plus dexamethasone compared
      with a 5HT(3) antagonist plus dexamethasone for prevention of acute and delayed
      emesis after high-dose cisplatin. Furthermore, the study sought to confirm that
      addition of MK-869 to a 5HT(3) antagonist plus dexamethasone was more effective
      than just the 5HT(3) antagonist plus dexamethasone for prevention of acute and
      delayed emesis. METHODS: This multicenter, double-blind, parallel-group trial in
      351 cisplatin-naive patients evaluated prevention of acute (0 to 24 hours) and
      delayed emesis (primary efficacy parameter; days 2 to 5) after cisplatin (> or
      =70 mg/m(2)). Patients were randomized to four groups (I to IV) (n = number
      randomized; number evaluable): granisetron (10 microg/kg intravenously) pre
      cisplatin followed by placebo on days 2 to 5 (group I) (n = 90; 90); granisetron
      and MK-869 (400 mg PO [by mouth]) pre-cisplatin, followed by MK-869 (300 mg PO)
      on days 2 to 5 (group II) (n = 86; 84); MK-869 (400 mg PO) the evening before and
      pre-cisplatin, followed by MK-869 (300 mg PO) on days 2 to 5 (group III) (n = 89;
      88); or MK-869 (400 mg PO) pre-cisplatin, followed by MK-869 (300 mg PO) on days
      2 to 5 (group IV) (n = 86; 84). All patients also received dexamethasone (20 mg
      PO) before cisplatin. Additional medication was available to treat emesis or
      nausea at any time. RESULTS: In the acute period, 57%, 80%, 46%, and 43% of
      patients were without emesis in groups I, II, III, and IV, respectively (P <.01
      for group II v group I). In the delayed period, the proportion of patients
      without emesis in groups I, II, III, and IV was 29%, 63%, 51%, and 57%,
      respectively (P <.01 for groups II, III, and IV v group I). The distribution of
      nausea scores in the delayed period was lower when comparing group II with group
      I (P <.05 for days 1 to 5 and days 2 to 5). One serious adverse event (dizziness)
      was rated as possibly related to MK-869. CONCLUSION: Once daily oral
      administration of MK-869 was effective in reducing delayed emesis and nausea
      after high-dose cisplatin. However, the combination of the 5HT3 antagonist plus
      dexamethasone was numerically superior to MK-869 plus dexamethasone in reducing
      acute emesis. Confirming and extending previous findings, the triple combination
      of a 5HT(3) antagonist, MK-869, and dexamethasone provided the best control of
      acute emesis.

PMID- 11251008
TI  - Discussing adjuvant cancer therapy.
AB  - PURPOSE: To document the adequacy of patient information in oncology
      consultations concerning adjuvant therapy and explore predictors of physician
      communication patterns, treatment decisions, patient information recall, and
      satisfaction. PATIENTS AND METHODS: Retrospective analysis of audiotapes and
      verbatim transcripts of 101 initial adjuvant therapy consultations with medical
      and radiation oncologists was undertaken. Content analysis, data on communication
      patterns, treatment decisions, patient anxiety, satisfaction, and information
      recall were collected. Predictors of physician communication, treatment
      decisions, recall, and satisfaction with the consultation were identified.
      RESULTS: The majority of patients were well informed of their prognosis, benefits
      and risks of therapy, and alternative management options. Only half were asked
      about preferences for information or decision-making involvement. Predictors of
      information detail given include patient sex, age, occupation, and education.
      Radiation and medical oncologists express prognosis and treatment benefit using
      similar phrases. When offered the chance to delay decision-making, most patients
      do so (P <.01). Final treatment decisions appear to be influenced by the
      presentation of choice in treatment options by the oncologist and whether the
      treatment decision was made during the initial consultation (P <.01). Information
      recall was not influenced by communication factors. Patients receiving less
      detailed information had slightly higher satisfaction with the consultation (P
      =.03). More anxious patients tended to be less satisfied (P =.07). CONCLUSION:
      The optimal way to discuss adjuvant therapy is undefined. More emphasis can be
      placed on soliciting patient preferences for information and decision-making
      involvement and tailoring both to the needs of the individual patient. Providing
      choice in treatment and delaying decision-making may affect the patient's
      treatment decision.

PMID- 11251009
TI  - Polymorphisms of the repeated sequences in the enhancer region of the thymidylate
      synthase gene promoter may predict downstaging after preoperative chemoradiation
      in rectal cancer.
AB  - PURPOSE: Thymidylate synthase (TS) is an important target enzyme for the
      fluoropyrimidines. TS gene promoter possesses regulatory tandemly repeated (TR)
      sequences that are polymorphic in humans, depending on ethnic factors. These
      polymorphisms have been reported to influence TS expression. TS expression levels
      affect tumor downstaging after preoperative fluoruracil (5-FU)-based
      chemoradiation. Tumor downstaging correlates with improved local control and
      disease-free survival. The aim of this study is to correlate TR polymorphisms
      with downstaging and disease-free survival. PATIENTS AND METHODS: Sixty-five
      patients with rectal cancer underwent tumor resection after preoperative 5-FU
      based chemoradiation. Tumor downstaging was evaluated by comparing the
      pretreatment T stage with the pathologic stage observed in the surgical specimen.
      TS polymorphism genotype was determined by polymerase chain reaction
      amplification of the corresponding TS promoter region, and products of
      amplification were electrophoresed, obtaining products of 220 bp (2/2), 248 bp
      (3/3), or both (2/3). The TS polymorphism genotype results were subsequently
      compared with the downstaging observed and with disease-free survival. RESULTS:
      Patients who were homozygous for triple TR (3/3) had a lower probability of
      downstaging than patients who were homozygous with double TR or heterozygous
      patients (2/2 and 2/3): 22% versus 60% (P =.036; logistic regression).
      Furthermore, a trend toward improved 3-year disease-free survival was detected in
      the 2/2 and 2/3 groups, compared with that in the 3/3 group (81% v 41%; P =.17).
      CONCLUSION: This preliminary study suggests that TS repetitive-sequence
      polymorphisms are predictive for tumor downstaging. TR sequences in TS promoter
      may be useful as a novel means of predicting response to preoperative 5-FU-based
      chemoradiation.

PMID- 11251010
TI  - Fluorouracil plus leucovorin as effective adjuvant chemotherapy in curatively
      resected stage III colon cancer: results of the trial adjCCA-01.
AB  - PURPOSE: Adjuvant postoperative treatment with fluorouracil (5-FU) and levamisole
      in curatively resected stage III colon cancer significantly reduces the risk of
      cancer recurrence and improves survival. Biochemical modulation of 5-FU with
      leucovorin has resulted in increased remission rates in metastatic colorectal
      cancer, thus reflecting an increased tumor-cell kill. The impact of 5-FU plus
      leucovorin on survival and tumor recurrence was analyzed in comparison with the
      effects of 5-FU plus levamisole in the prospective multicentric trial adjCCA-01.
      PATIENTS AND METHODS: Patients with a curatively resected International Union
      Against Cancer stage III colon cancer were stratified according to T, N, and G
      category and randomly assigned to receive one of the two adjuvant treatment
      schemes: 5-FU 400 mg/m(2) body-surface area intravenously in the first
      chemotherapy course, then 450 mg/m(2) x 5 days; 12 cycles, plus leucovorin 100
      mg/m(2) (arm A), or 5-FU plus levamisole (Moertel scheme; arm B). RESULTS: Six
      hundred eighty (96.9%) of 702 patients enrolled onto this study were eligible.
      After a median follow-up time of 46.5 months, the 5-FU plus leucovorin
      combination significantly improved disease-free survival (P =.037) and
      significantly decreased overall mortality (P =.0089) in comparison with 5-FU plus
      levamisole. In a multivariate proportional hazards model, adjuvant chemotherapy
      emerged as a significant prognostic factor for survival (P =.0059) and disease
      free survival (P =.03). Adjuvant treatment with 5-FU plus levamisole as well as
      with 5-FU plus leucovorin was generally well tolerated; only a minority of
      patients experienced grade 3 and 4 toxicities. CONCLUSION: After a curative
      resection of a stage III colon cancer, adjuvant treatment with 5-FU plus
      leucovorin is generally well tolerated and significantly more effective than 5-FU
      plus levamisole in reducing tumor relapse and improving survival.

PMID- 11251011
TI  - Circulating neuroblastoma cells detected by reverse transcriptase polymerase
      chain reaction for tyrosine hydroxylase mRNA are an independent poor prognostic
      indicator in stage 4 neuroblastoma in children over 1 year.
AB  - PURPOSE: In this prospective, multicenter study, the independent prognostic power
      of neuroblastoma cells detected by reverse transcriptase polymerase chain
      reaction (RT-PCR) for tyrosine hydroxylase (TH) mRNA was evaluated. PATIENTS AND
      METHODS: The clinical significance of disease detected by RT-PCR in peripheral
      blood from children at diagnosis was compared with established prognostic markers
      [ie, age, lactate dehydrogenase (LDH), neuron-specific enolase, ferritin, and
      MYCN gene amplification] by multivariate analysis. The value of disease detection
      by RT-PCR during treatment and follow-up was also examined. RESULTS: TH mRNA was
      detected in peripheral blood from 33 of 49 (67%) children with stage 4
      neuroblastoma > 1 year old at diagnosis and was a significant predictive factor
      for overall survival [hazard ratio (HR) = 2.40, 95% confidence interval (CI) 1.19
      to 4.84, P =.014) and event-free survival (HR = 2.09, 95% CI 1.06 to 4.17, P
      =.034) in a multivariate analysis. Detection of disease in blood from clinically
      disease-free children was related to increased risk of death (HR 2.54, 95% CI
      1.42 to 4.55, P =.0014). CONCLUSION: TH mRNA in peripheral blood of children with
      neuroblastoma is a poor prognostic indicator, reflecting the propensity for
      dissemination via the bloodstream. When combined with a serum LDH > 1500 IU/L,
      this is the most powerful poor prognostic model at diagnosis for children > 1
      year old with stage 4 disease. The detection of TH mRNA in peripheral blood from
      clinically disease-free children is related to increased risk of relapse and
      death.

PMID- 11251012
TI  - Immediate neurocognitive effects of methylphenidate on learning-impaired
      survivors of childhood cancer.
AB  - PURPOSE: To test if methylphenidate (MPH) has an objective beneficial effect on
      immediate performance on tests of neurocognitive functions among learning
      impaired survivors of childhood acute lymphoblastic leukemia (ALL) and malignant
      brain tumors (BT). PATIENTS AND METHODS: From July 1, 1997 through December 31,
      1998, 104 long-term survivors of childhood ALL or a malignant BT completed
      neurocognitive screening for learning impairments and concurrent problems with
      sustained attention. Eligibility criteria for the MPH trial included an estimated
      intelligence quotient greater than 50, academic achievement in the 16(th)
      percentile or lower for age in reading, math, or spelling, and an ability to
      sustain attention on a computerized version of the Conners' Continuous
      Performance Test (CPT) in the 16(th) percentile or lower for age and sex. Of the
      104, 32 (BT, n = 25; ALL, n = 7) were eligible on the basis of these a priori
      criteria for a randomized, double-blinded, placebo-controlled trial of MPH. The
      patients ingested a placebo (lactose) or MPH (0.6 mg/kg; 20 mg maximum) and
      repeated selected portions of the screening battery 90 minutes later. RESULTS:
      Compared to the 17 patients randomized to the placebo group, the 15 patients
      randomized to the MPH group had a significantly greater improvement on the CPT
      for sustained attention (errors of omission, P =.015) and overall index (P =.008)
      but not for errors of commission (indicative of impulsiveness) nor reaction
      times. A trend for greater improvement in the MPH group on a measure of verbal
      memory failed to reach statistical significance. No trend was observed for MPH
      effectiveness in improving learning of a word association task. No significant
      side effects from MPH were observed. CONCLUSION: MPH resulted in a statistically
      significant improvement on measures of attention abilities that cannot be
      explained by placebo or practice effects.

PMID- 11251013
TI  - Reliability and validity of the functional assessment of cancer therapy-ovarian.
AB  - PURPOSE: To report the reliability and validity of the Functional Assessment of
      Cancer Therapy-Ovarian (FACT-O) in a consecutive series of outpatients with
      epithelial ovarian cancer. PATIENTS AND METHODS: Two hundred thirty-two ovarian
      cancer patients attending an outpatient gynecologic oncology clinic completed
      questionnaires at baseline. The patients' FACT-O scores were compared with their
      performance status, disease stage, treatment status, and other factors
      hypothesized to be related to quality of life. Patients received a second
      questionnaire either one week after baseline to assess the instrument's test
      retest reliability and/or two months after baseline to evaluate its sensitivity
      to change in performance status. RESULTS: Internal consistency and test-retest
      reliability of the FACT-O were adequate. Overall, the scales correlated with
      other measures as expected; all correlations were in the hypothesized direction.
      Patients with advanced disease, poor performance status, and who were receiving
      active treatment had lower scores on physical, functional, and ovarian cancer
      specific scales. The total FACT-O and emotional well-being scores were lower for
      patients with poor performance status and patients in active treatment. The FACT
      O total and all subscale scores except emotional well-being were sensitive to
      decreases in performance status. CONCLUSION: Overall, the FACT-O provides a
      reliable and valid assessment of the quality of life of women with ovarian
      cancer, and is appropriate as a brief quality of life assessment in clinical
      trials and descriptive studies.

PMID- 11251015
TI  - Phase I trial of oral green tea extract in adult patients with solid tumors.
AB  - PURPOSE: This trial was designed to determine the maximum-tolerated dose,
      toxicity, and pharmacology of oral green tea extract (GTE) once daily or three
      times daily. PATIENTS AND METHODS: Cohorts of three or more adult cancer patients
      were administered oral GTE with water after meals one or three times daily for 4
      weeks, to a maximum of 6 months, depending on disease response and patient
      tolerance. Pharmacokinetic analyses were encouraged but optional. RESULTS: Dose
      levels of 0.5 to 5.05 g/m(2) qd and 1.0 to 2.2 g/m(2) tid were explored. A total
      of 49 patients were studied. PATIENT CHARACTERISTICS: median age, 57 years
      (range, 27 to 77 years); 23 patients were women (47%); 98% had a Zubrod PS of 1%;
      98% had PS of 1; and 21 had non-small-cell lung, 19 had head & neck cancer, three
      had mesothelioma, and six had other. Mild to moderate toxicities were seen at
      most dose levels and promptly reversed on discontinuation of GTE. Dose-limiting
      toxicities were caffeine related and included neurologic and gastrointestinal
      effects. The maximum-tolerated dose was 4.2 g/m(2) once daily or 1.0 g/m(2) three
      times daily. No major responses occurred; 10 patients with stable disease
      completed 6 months of GTE. Pharmacokinetic analyses found accumulation of
      caffeine levels that were dose dependent, whereas epigallocatechin gallate levels
      did not accumulate nor appear dose related. CONCLUSION: A dose of 1.0 g/m(2) tid
      (equivalent to 7 to 8 Japanese cups [120 mL] of green tea three times daily) is
      recommended for future studies. The side effects of this preparation of GTE were
      caffeine related. Oral GTE at the doses studied can be taken safely for at least
      6 months.

PMID- 11251014
TI  - Localized Ewing tumor of bone: final results of the cooperative Ewing's Sarcoma
      Study CESS 86.
AB  - PURPOSE: Cooperative Ewing's Sarcoma Study (CESS) 86 aimed at improving event
      free survival (EFS) in patients with high-risk localized Ewing tumor of bone.
      PATIENTS AND METHODS: We analyzed 301 patients recruited from January 1986 to
      July 1991 (60% male; median age 15 years). Tumors of volume >100 mL and/or at
      central-axis sites qualified patients for "high risk" (HR, n = 241), and small
      extremity lesions for "standard risk" (SR, n = 52). Standard-risk patients
      received 12 courses of vincristine, cyclophosphamide, and doxorubicin alternating
      with actinomycin D (VACA); HR patients received ifosfamide instead of
      cyclophosphamide (VAIA). Tumor sites were pelvis (27%), other central axis (28%),
      femur (19%), or other extremity (26%). The initial tumor volume was <100 mL in
      33% of cases and > or =100 mL in 67%. Local therapy was surgery (23%), surgery
      plus radiotherapy (49%), or radiotherapy alone (28%). Event-free survival rates
      were estimated by Kaplan-Meier analyses, comparisons were done by log-rank test,
      and risk factors were analyzed by Cox models. RESULTS: On May 1, 1999 (median
      time under study, 133 months), the 10-year EFS was 0.52. Event-free survival did
      not differ between SR-VACA (0.52) and HR-VAIA (0.51, P =.92). Tumor volume of
      >200 mL (EFS, 0.36 v 0.63 for smaller tumors; P =.0001) and poor histologic
      response (EFS, 0.38 v 0.64 for good responders; P =.0007) had negative impacts on
      EFS. In multivariate analyses, small tumor volumes of <200 mL, good histologic
      response, and VAIA chemotherapy augured for fair outcome. Six of 301 patients
      (2%) died under treatment, and four patients (1.3%) developed second
      malignancies. CONCLUSION: Fifty-two percent of CESS 86 patients survived after
      risk-adapted therapy. High-risk patients seem to have benefited from intensified
      treatment that incorporated ifosfamide.

PMID- 11251016
TI  - Development of inhalational agents for oncologic use.
AB  - Because regional chemotherapy has been useful in treatment and palliation of many
      cancer types, the concept of delivering drugs by inhalation for the treatment of
      cancers in the lung is attractive. Much higher local drug exposure can be
      achieved with total doses considerably lower than those required for systemic
      administration, resulting in lower exposure of nonrespiratory tract tissues to
      potentially toxic drugs. Regional delivery of chemotherapy to the respiratory
      tract has been shown to have activity in preclinical and clinical studies.
      Technical improvements in delivery methods have now made it possible to conduct
      trials of inhalational agents, both to treat cancers affecting the respiratory
      tract and to deliver other drugs used in cancer patients. This review discusses
      the rationale of drug delivery by the inhalational route, its technical
      challenges, preclinical and clinical experiences, limitations, and promise.

PMID- 11251017
TI  - Clinical trial designs for the early clinical development of therapeutic cancer
      vaccines.
AB  - There are major differences between therapeutic tumor vaccines and
      chemotherapeutic agents that have important implications for the design of early
      clinical trials. Many vaccines are inherently safe and do not require phase I
      dose finding trials. Patients with advanced cancers and compromised immune
      systems are not good candidates for assessing either the toxicity or efficacy of
      therapeutic cancer vaccines. The rapid pace of development of new vaccine
      candidates and the variety of possible adjuvants and modifications in method of
      administration makes it important to use efficient designs for clinical screening
      and evaluation of vaccine regimens. We review the potential advantages of a wide
      range of clinical trial designs for the development of tumor vaccines. We address
      the role of immunological endpoints in early clinical trials of tumor vaccines,
      investigate the design implications of attempting to use disease stabilization as
      an end point and discuss the difficulties of reliably utilizing historical
      control data. Several conclusions for expediting the clinical development of
      effective cancer vaccines are proposed.

PMID- 11251018
TI  - Primary mediastinal B-cell lymphoma: a review of pathology and management.
AB  - PURPOSE: Primary mediastinal B-cell lymphoma (PMBL) is recognized as a separate
      disease entity in the REAL classification. There is uncertainty about the
      relevance and especially the optimal management of this disorder. In this review,
      we discuss clinical presentation, pathology, pathobiology, and management of PMBL
      in order to provide a platform for initiation of further clinical and biologic
      studies. MATERIALS AND METHODS: Studies were identified through a MEDLINE search
      and from the bibliographies of relevant articles. RESULTS: PMBL is a tumor of
      young adults who present with a rapidly proliferating tumor. At diagnosis, the
      tumor is usually limited to intrathoracic organs. Spread to parenchymal organs
      such as liver, kidneys, and CNS is common at recurrence. Fibrosis and the
      presence of so-called clear cells are distinctive morphologic features of PMBL,
      although they are not pathognomonic or even necessary for diagnosis. On the other
      hand, biologic features relating to oncogene rearrangement and overexpression as
      well as cytogenetic features clearly differentiate PMBL from other types of
      diffuse large B-cell lymphoma. Phase II studies and retrospective series indicate
      cure rates that range from 38% to 88%. The role of chemotherapy, radiation, and
      high-dose chemotherapy with stem cell rescue in the management of PMBL is
      reviewed. CONCLUSION: PMBL has unique clinical and biologic characteristics that
      are radically different from those of other types of diffuse large B-cell
      lymphoma. Although relatively rare, its aggressive growth and its occurrence in
      young patients increase the clinical relevance of this entity. The consistent
      recognition and study of PMBL will allow the development of new approaches to its
      management.

PMID- 11251019
TI  - 2000 update of recommendations for the use of tumor markers in breast and
      colorectal cancer: clinical practice guidelines of the American Society of
      Clinical Oncology.
AB  - OBJECTIVE: To update the 1997 clinical practice guidelines for the use of tumor
      marker tests in the prevention, screening, treatment, and surveillance of breast
      and colorectal cancers. These guidelines are intended for use in the care of
      patients outside of clinical trials. OPTIONS: Six tumor markers for colorectal
      cancer and eight for breast cancer were considered. They could be recommended or
      not for routine use or for special circumstances. In addition to carcinoembryonic
      antigen (CEA) and CA 15-3, CA 27.29 was also considered among the serum tumor
      markers for breast cancer. OUTCOMES: In general, the significant health outcomes
      identified for use in making clinical practice guidelines (overall survival,
      disease-free survival, quality of life, lesser toxicity, and cost-effectiveness)
      were used. EVIDENCE: A computerized literature search from 1994 to March 1999 was
      performed. VALUES: The same values for use, utility, and levels of evidence were
      used by the committee. BENEFITS, HARMS, AND COSTS: The same benefit, harms, and
      costs were used. RECOMMENDATION: Changes were recommended (see Appendix).
      VALIDATION: The updated recommendations were validated by external review by the
      American Society of Clinical Oncology's (ASCO's) Health Services Research
      Committee and by ASCO's Board of Directors. SPONSOR: American Society of Clinical
      Oncology.

PMID- 11251020
TI  - Postoperative adjuvant chemoradiation therapy for patients with resected gastric
      cancer: intergroup 116.

PMID- 11251021
TI  - Preoperative chemoradiotherapy using taxanes for locally advanced esophageal
      carcinoma.

PMID- 11251022
TI  - Safety of sentinel lymph node dissection and significance of cytokeratin
      micrometastases.

PMID- 11251023
TI  - Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin's
      lymphoma: concerns about omissions in the data presented.

PMID- 11251025
TI  - Hypercalcemic crisis.
AB  - Hypercalcemia may decompensate from a more or less chronic status into a critical
      and life-threatening condition, hypercalcemic crisis. In the majority of cases,
      primary hyperparathyroidism is the cause; humoral hypercalcemia of malignancy or
      rarer conditions of hypercalcemia will decompensate less often. The leading
      symptoms that characterize the crisis are oliguria and anuria as well as
      somnolence and coma. After a hypercalcemic crisis is recognized, an emergency
      diagnostic program has to be followed either to prove or to exclude primary
      hyperparathyroidism. In the first case, surgical neck exploration is the only way
      to avoid fatal outcome. The diagnostic program should be performed within hours;
      during this time, serum calcium should be lowered. Treatment of choice is
      hemodialysis against a calcium-free dialysate. Bisphosphonates could be useful as
      adjuvant drugs.

PMID- 11251026
TI  - Treatment of severe hyponatremia: conventional and novel aspects.
AB  - Hyponatremia is a frequent electrolyte disorder. A hyponatremia is called acute
      severe (<115 mM) when the duration has been <36 to 48 h. Such patients often have
      advanced symptoms as a result of brain edema. Acute severe hyponatremia is a
      medical emergency. It should be corrected rapidly to approximately 130 mM to
      prevent permanent brain damage. In contrast, in chronic severe hyponatremia (>4
      to 6 d), there is no brain edema and symptoms are usually mild. In such patients,
      a number of authors have recommended a correction rate <0.5 mM/h to approximately
      130 mM to minimize the risk of cerebral myelinolysis. Sometimes it is not
      possible to diagnose whether a severe hyponatremia is acute or chronic. In such
      cases, an initial imaging procedure is helpful in deciding whether rapid or slow
      correction should be prescribed. The modalities of treatment of severe
      hyponatremia have so far consisted of infusions of hypertonic saline plus fluid
      restriction. In the near future, vasopressin antagonists will become available.
      Preliminary experience has already demonstrated their efficiency of inducing a
      sustained water diuresis and a correction of hyponatremia.

PMID- 11251027
TI  - Lactic acidosis update for critical care clinicians.
AB  - Lactic acidosis is a broad-anion gap metabolic acidosis caused by lactic acid
      overproduction or underutilization. The quantitative dimensions of these two
      mechanisms commonly differ by 1 order of magnitude. Overproduction of lactic
      acid, also termed type A lactic acidosis, occurs when the body must regenerate
      ATP without oxygen (tissue hypoxia). Circulatory, pulmonary, or hemoglobin
      transfer disorders are commonly responsible. Overproduction of lactate also
      occurs with cyanide poisoning or certain malignancies. Underutilization involves
      removal of lactic acid by oxidation or conversion to glucose. Liver disease,
      inhibition of gluconeogenesis, pyruvate dehydrogenase (thiamine) deficiency, and
      uncoupling of oxidative phosphorylation are the most common causes. The kidneys
      also contribute to lactate removal. Concerns have been raised regarding the role
      of metformin in the production of lactic acidosis, on the basis of individual
      case reports. The risk appears to be considerably less than with phenformin and
      involves patients with underlying severe renal and cardiac dysfunction. Drugs
      used to treat lactic acidosis can aggravate the condition. NaHCO(3) increases
      lactate production. Treatment of type A lactic acidosis is particularly
      unsatisfactory. NaHCO(3) is of little value. Carbicarb is a mixture of Na(2)CO(3)
      and NaHCO(3) that buffers similarly to NaHCO(3) but without net generation of
      CO(2). The results from animal studies are promising; however, clinical trials
      are sparse. Dichloroacetate stimulates pyruvate dehydrogenase and improves
      laboratory values, but unfortunately not survival rates, among patients with
      lactic acidosis. Hemofiltration has been advocated for the treatment of lactic
      acidosis, on the basis of anecdotal experiences. However, kinetic studies of
      lactate removal do not suggest that removal can counteract lactate production in
      any meaningful way. The ideal treatment is to stop acid production by treating
      the underlying disorder.

PMID- 11251029
TI  - Volume replacement in critically ill patients with acute renal failure.
AB  - Maintenance and restoration of intravascular volume are essential tasks of
      critical care management to achieve sufficient organ function and to avoid
      multiple organ failure in critically ill patients. Inadequate intravascular
      volume followed by impaired renal perfusion is the predominate cause of acute
      renal failure. Crystalloid solutions are the first choice to correct fluid and
      electrolyte deficits in these patients. However, in case of major hypovolemia,
      particularly in situations of increased capillary permeability, colloid solutions
      are indicated to achieve sufficient tissue perfusion. Whereas albumin should be
      avoided for correction of intravascular hypovolemia, synthetic colloids can
      restore intravascular volume and stabilize hemodynamic conditions. In addition to
      a faster, more effective and prolonged restoration of intravascular volume,
      colloid solutions are able to improve microcirculation. Of the synthetic
      colloids, hydroxyethyl starch (HES) solutions with a low in vivo molecular
      weight, such as HES 200/0.5, offer the best risk/benefit ratio. These solutions
      are safe with respect to effects on coagulation, platelets, reticuloendothelial
      system, and renal function, if used below their upper dosage limits. For patients
      with acute renal dysfunction, daily monitoring of renal function is necessary if
      colloids are required to stabilize hemodynamic conditions. In these patients,
      measurement of the colloidal osmotic pressure and adequate amounts of crystalloid
      solutions will reduce the risk of hyperoncotic renal failure. Of all colloids,
      gelatin and HES solutions with low in vivo molecular weight are preferred in
      these cases. In the very specific situation of kidney transplantation, colloid
      solutions should be administered in a restricted manner to organ donors and
      kidney recipients.

PMID- 11251028
TI  - Pathophysiologic features and prevention of human and experimental acute tubular
      necrosis.
AB  - Acute renal failure (ARF) remains a common and potentially devastating disorder
      that affects as many as 5% of all hospitalized patients, with a higher prevalence
      in patients in critical care units. The focus of this article is on categorizing
      recent pathophysiologic and clinically relevant developments in the field. The
      vascular and tubular factors in the pathogenesis of ARF, together with the
      potential mechanisms of recovery and repair of the injured kidney, are discussed.
      A number of experimental and clinical interventions to prevent. ARF are
      summarized. Although the clinical treatment of these patients is still largely
      supportive and many recent clinical trials showed rather negative results, it is
      hoped that basic research will provide therapeutic tools to improve the grim
      prognosis of this disease in the future.

PMID- 11251030
TI  - What is the renal replacement method of first choice for intensive care patients?
AB  - Renal replacement therapy for the patient with acute renal failure on the
      intensive care unit can be offered in several different formats: intermittent
      hemodialysis (IHD), continuous renal replacement therapy (CRRT), and slow low
      efficient daily dialysis (SLEDD). It is frequently claimed that CRRT offers
      several advantages over IHD, but most of these, such as correction of metabolic
      acidosis, better recovery of renal function, better clinical outcome due to
      application of biocompatible dialysis membranes, correction of malnutrition, and
      better removal of cytokines, are not corroborated by the results of controlled
      prospective studies. There is also no evidence that CRRT results in a better
      survival, compared with IHD. The only potential advantages of CRRT that stood the
      test of clinical evaluation (hemodynamic stability, correction of hypervolemia,
      better solute removal) can be offered as well by SLEDD. In addition, the latter
      strategy is less expensive because the same infrastructure is used as for IHD,
      while the patient is not immobilized continuously, which leaves time free for
      other activities such as nursing care and technical investigations. SLEDD is a
      relatively young technique, so thorough clinical studies are lacking.
      Nevertheless, the hypothesis is proposed that SLEDD offers a valuable alternative
      to the classical dialysis strategies, applied in the intensive care patient.

PMID- 11251031
TI  - New aspects of the treatment of nephrotic syndrome.
AB  - The nephrotic syndrome, caused by glomerulonephritis, diabetes mellitus, or
      amyloidosis, is still a therapeutic challenge. Newer therapeutic approaches may
      be sought in the fields of immunosuppression, nonspecific supportive measures,
      heparinoid administration, and removal of a supposed glomerular basement membrane
      toxic factor. In immunosuppression, the newer drugs now used in organ
      transplantation (cyclosporine, tacrolimus, and mycophenolate mofetil) can also be
      used in the treatment of glomerulonephritis. In nonspecific supportive treatment,
      angiotensin II receptor antagonists are now used in addition to angiotensin
      converting enzyme inhibitors. Positive effects of hydroxymethylglutaryl coenzyme
      A reductase inhibitors on the nephrotic syndrome have not yet been proven.
      Cyclooxygenase II inhibitors must be tested but probably have too many renal side
      effects, similar to those of nonsteroidal anti-inflammatory drugs. Heparinoids or
      glycosaminoglycans serve as polyanions and thus have protective effects on the
      negative charge of the glomerular basement membrane. They can now be administered
      as oral medications. The removal of a supposed glomerular basement membrane toxic
      factor that induces proteinuria has been attempted for 20 yr and now is usually
      performed using immunoadsorption. Especially in cases of recurrent nephrotic
      syndrome after renal transplantation for patients with glomerulonephritis, this
      approach has been successful in decreasing proteinuria, although in most cases
      its effect is not lasting but must be continuously renewed.

PMID- 11251032
TI  - Steroid-resistant kidney transplant rejection: diagnosis and treatment.
AB  - Decreases in transplant function may be attributable to a variety of conditions,
      including prerenal and postrenal failure, cyclosporin A (CsA) toxicity, polyoma
      nephritis, recurrent glomerulonephritis, and rejection. The diagnosis of
      rejection should therefore be made on the basis of a transplant biopsy of
      adequate size, before the initiation of any therapy. Pulse steroid treatment
      (three to five 0.25- to 1.0-g pulses of methylprednisolone, administered
      intravenously) is the usual first-line therapy and has a 60 to 70% success rate,
      although orally administered prednisone (0.25 g) may be just as efficacious. Even
      if reverted, any rejection should trigger an at least temporary increase in basal
      immunosuppression, consisting of an increase in CsA or tacrolimus target levels,
      the addition of steroids or an increase in their dosage, the addition of
      mycophenolate mofetil, or a switch from CsA to tacrolimus. The addition of
      rapamycin or its RAD derivative may fulfill the same purpose. Steroid resistance
      should not be assumed before the fifth day of pulse steroid treatment, although
      histologic features of vascular rejection may indicate the need for more
      aggressive treatment earlier. Steroid-resistant rejection is traditionally
      treated with poly- or monoclonal antilymphocytic antibodies, with success rates
      of 60 to 70%. Their potential benefit must be carefully balanced against the
      risks of infection and lymphoma. More recently, mycophenolate mofetil has been
      successfully used to treat steroid-resistant rejection, but only of the
      interstitial (cellular) type. Switching from CsA to tacrolimus for treating
      recurrent or antibody-resistant rejection is successful in approximately 60% of
      cases. Plasmapheresis and intravenously administered Ig have been used in some
      desperate cases, with surprising success. Because none of the available drugs has
      a significantly better profile of therapeutic versus adverse effects, the
      possible benefits of continued rejection therapy must be continuously balanced
      with the potential for serious, sometimes fatal, side effects.

PMID- 11251033
TI  - Monitoring of organ dysfunction in sepsis/systemic inflammatory response
      syndrome: novel strategies.
AB  - Sepsis and systemic inflammatory response syndrome-induced severe disruption of
      microcirculation and consecutive tissue hypoxia is considered a key factor in the
      development of organ dysfunction and multiple organ failure. The conventionally
      measured global variables such as lactate or macrohemodynamic parameters using a
      pulmonary artery catheter do not adequately mirror microcirculatory disturbances.
      Evaluation of the severity of microcirculatory distress and the effectiveness of
      resuscitation strategies requires new clinical technologies aimed at the
      microcirculation. It is anticipated that novel techniques such as optical
      spectroscopy and intelligent biosensors will play a major role in the development
      of new monitoring systems. In general, the current monitoring of organ
      dysfunction is characterized by a trend from invasive to noninvasive and "safe"
      techniques, which provide bedside or even on-line monitoring and allow a more
      precise and earlier detection of organ dysfunction. Techniques for the assessment
      of regional perfusion and microcirculatory bioenergetics to direct therapeutic
      procedures are expected to refine and optimize clinical treatment of critically
      ill patients in the future. This article addresses the question of which
      variables should be monitored, what is feasible, and what is valid for
      therapeutic consequences. Recent developments in monitoring of macro- and
      microcirculation and organ-specific dysfunction, e.g., lung, kidney, are
      described with respect to their advantages and limitations, and future directions
      are outlined.

PMID- 11251034
TI  - Effects of genomic polymorphisms on the course of sepsis: is there a concept for
      gene therapy?
AB  - Sepsis and its sequelae are still a major cause of morbidity and mortality on
      today's intensive care units. The evidence that endogenous mediators actually
      mediate the individual's response to infection has led to various approaches to
      assess the individual's contribution to the course of the disease. The role of an
      individual's genetic background and predisposition for the extent of inflammatory
      responses is determined by variabilities of genes encoding endogenous mediators
      that constitute the pathways of inflammation. Primary responses in inflammation
      are mediated by proinflammatory cytokines such as tumor necrosis factor and
      interleukin 1. Conversely, anti-inflammatory mediators are released and may
      induce a state of immunosuppression in sepsis. Pro- and anti-inflammatory
      responses contribute to the outcome of patients with systemic inflammation and
      sepsis. Therefore, all genes encoding proteins involved in the transduction of
      inflammatory processes are candidate genes to determine the human genetic
      background that is responsible for interindividual differences in systemic
      inflammatory responses to injury. The genetically determined capacity of cytokine
      production and release, heat shock protein expression, nitric oxide synthase
      activity, gene polymorphisms of coagulation factors or factors of the innate
      immune system-like defensins, and other genes involved in inflammation may
      contribute to a wide range of clinical manifestations of an inflammatory disease.
      Genomic information may be used to identify groups of patients with a high risk
      of developing severe sepsis and multiple organ dysfunction, and determining which
      patients will benefit from antimediator strategies because of their genetic
      determination to high cytokine release in the inflammatory response will be the
      subject of future trials.

PMID- 11251035
TI  - Therapeutic options for the treatment of impaired gut function.
AB  - Tissue hypoxia, especially in the splanchnic area, is still considered to be an
      important cofactor in the pathogenesis of multiple organ failure. Therefore, the
      specific effects of the various therapeutic interventions on splanchnic perfusion
      and oxygenation are of particular interest. Restoring and maintaining oxygen
      transport and tissue oxygenation is the most important step in the supportive
      treatment of patients with sepsis and impaired gut perfusion. Therefore,
      supportive treatment should be focused on an adequate volume resuscitation and
      appropriate use of vasoactive drugs. Adequate volume loading may be the most
      important step in the treatment of patients with septic shock. An elevated oxygen
      delivery may be beneficial in some patients, but the increase of oxygen delivery
      should be guided by the measurement of parameters assessing global and regional
      oxygenation. Forcing an elevation in oxygen delivery by the use of very high
      dosages of catecholamines can be harmful. Vasopressors should be used for
      achieving an adequate perfusion pressure. For norepinephrine, no negative effects
      on gut perfusion have been demonstrated. Epinephrine and dopamine should be
      avoided because they seem to redistribute blood flow away from the splanchnic
      region. There are no convincing data yet to support the routine use of low-dose
      dopamine or dopexamine to improve an impaired gut perfusion. There is even
      evidence that low-dose dopamine may reduce the mucosal perfusion in the gut in
      some patients. It has been suggested that dopexamine can improve splanchnic
      perfusion, but because these effects remain somewhat controversial, a general
      recommendation for dopexamine to improve gut perfusion is not justified.

PMID- 11251036
TI  - Immunomodulation in septic shock: hydrocortisone differentially regulates
      cytokine responses.
AB  - Cortisol is known to be an immunomodulatory hormone that exerts suppressive and
      permissive effects on the immune response. Little is known regarding the
      evolution of the cytokine response in human septic shock in the presence of
      hypercortisolemia induced by infusion of stress doses of hydrocortisone. Twenty
      four consecutive patients with high-out-put circulatory failure (cardiac index,
      >4 liters/min per m(2)) who met the American College of Chest Physicians/Society
      of Critical Care Medicine Consensus Conference Committee criteria for septic
      shock were enrolled in a prospective, double-blind study. The severity of illness
      at the time of enrollment was graded using the Acute Physiology and Chronic
      Health Evaluation II system, and the evolution of sepsis-induced organ
      dysfunction syndrome was assessed using Sepsis-Related Organ Failure Assessment
      scores. After randomization, hyper-cortisolemia was induced in 12 patients by
      infusion of 100 mg of hydrocortisone, followed by continuous infusion of 0.18
      mg/kg per h. Levels of the circulating cytokines tumor necrosis factor alpha
      (TNF), interleukin 6 (IL-6), IL-8, and IL-10 were serially measured at
      prospectively defined time points during the first 5 d after randomization. The
      infusion of hydrocortisone was associated with significant reductions in serum IL
      6 and IL-8 levels and with earlier resolution of the sepsis-induced organ
      dysfunction syndrome. IL-6 levels started to differ between the groups on day 5.
      The TNF and IL-10 responses were not altered by hydrocortisone infusion.
      Hydrocortisone infusion in septic shock differentially regulated the cytokine
      responses. IL-6 and IL-8 levels decreased significantly and IL-6 levels differed
      between the groups, whereas TNF and IL-10 levels were not affected by
      hydrocortisone. Stress doses of hydrocortisone may be a valuable immunomodulatory
      therapy for septic shock.

PMID- 11251037
TI  - Extracorporeal detoxification using the molecular adsorbent recirculating system
      for critically ill patients with liver failure.
AB  - Liver failure resulting from different causes and its concomitant complications
      represent difficult-to-treat conditions with high mortality rates, despite
      improved therapeutic modalities in intensive care medicine. The accumulation of
      albumin-bound metabolites that are normally cleared by the liver, such as
      bilirubin and bile acids, contributes substantially to the development of
      multiorgan dysfunction in these clinical situations. The molecular adsorbent
      recirculating system (MARS) represents a cell-free, extracorporeal, liver
      assistance method for the selective removal of albumin-bound substances.
      Moreover, it enables the removal of excess water and water-soluble substances via
      an inbuilt dialysis step. Since 1993, >400 patients have been treated in 53
      centers in Europe, the United States, and Asia. Diseases treated with MARS
      included acute exacerbation of chronic hepatic failure, hepatorenal syndrome,
      acute hepatic failure, and primary nonfunction/poor function after liver
      transplantation and major liver resection. Treatments were well tolerated. No
      severe adverse events were observed. Six- to 8-h MARS treatments resulted in
      significant (P < 0.05) removal of bilirubin, bile acids, tryptophan, short- and
      middle-chain fatty acids, aromatic amino acids, and ammonia. Clearance rates for
      strongly albumin-bound substances were between 10 and 60 ml/min. The removal of
      albumin-bound toxins resulted in decreases in hepatic encephalopathy, increases
      in mean arterial pressure, and improvements in kidney and liver function. In the
      first randomized clinical trial of the MARS method for treatment of the
      hepatorenal syndrome, significant prolongation of survival was observed for the
      MARS-treated group. It is concluded that the MARS method can contribute to the
      treatment of critically ill patients with liver failure and different underlying
      diseases.

PMID- 11251038
TI  - Patient data management systems in critical care.
AB  - Electronic patient data management systems (PDMS) were clinically used for the
      first time in the 1970s. Their purpose was to automatically document vital
      parameters sampled by monitors and to replace handwritten medical files. Because
      of the continuous development of computer technology, however, demands on PDMS
      have increased immensely. PDMS are currently expected to assist clinicians at
      every level of intensive care, i.e., at the strategic level of physicians' orders
      and prescriptions, at the operational level, and at the administrative level. In
      1994, a PDMS (CareVue; Agilent Technologies) was installed and further developed
      in the anesthesiologic intensive care unit of the university hospital in
      Tubingen. The goals of this article were to describe the current demands on PDMS,
      to communicate our experiences in implementing a PDMS, to list the costs of
      purchasing and maintaining the system, and to report on the acceptance among
      physicians and nursing personnel. This article may assist new users in planning
      for, purchasing, and implementing a PDMS.

PMID- 11251039
TI  - Amine uptake and peptide hormone secretion: APUD cells in a new landscape.

PMID- 11251040
TI  - Hey presto! Electrophysiological characterisation of prestin, a motor protein
      from outer hair cells, transfected into kidney cells.

PMID- 11251041
TI  - Increased Ca2+ buffering enhances Ca2+-dependent process.

PMID- 11251042
TI  - The facilitated component of intestinal glucose absorption.
AB  - Over the last decade, a debate has developed about the mechanism of the passive
      or 'diffusive' component of intestinal glucose absorption and, indeed, whether it
      even exists. Pappenheimer and colleagues have proposed that paracellular solvent
      drag contributes a passive component, which, at high concentrations of sugars
      similar to those in the jejunal lumen immediately after a meal, is severalfold
      greater than the active component mediated by the Na+-glucose cotransporter
      SGLT1. On the other hand, Ferraris & Diamond maintain that the kinetics of
      glucose absorption can be explained solely in terms of SGLT1 and that a passive
      or paracellular component plays little, if any, part. Recently, we have provided
      new evidence that the passive component of glucose absorption exists, but is in
      fact facilitated since it is mediated by the rapid, glucose-dependent activation
      and recruitment of the facilitative glucose transporter GLUT2 to the brush-border
      membrane; regulation involves a protein kinase C (PKC)-dependent pathway
      activated by glucose transport through SGLT1 and also involves mitogen-activated
      protein kinase (MAP kinase) signalling pathways. This topical review seeks to
      highlight the significant points of the debate, to show how our proposals on
      GLUT2 impact on different aspects of the debate and to look at the regulatory
      events that are likely to be involved in the short-term regulation of sugar
      absorption during the assimilation of a meal.

PMID- 11251043
TI  - The stoichiometry of the electrogenic sodium bicarbonate cotransporter NBC1 is
      cell-type dependent.
AB  - 1. The pancreatic variant of the sodium bicarbonate cotransporter, pNBC1,
      mediates basolateral bicarbonate influx in the exocrine pancreas by coupling the
      transport of bicarbonate to that of sodium, with a 2 HCO3-:1 Na+ stoichiometry.
      The kidney variant, kNBC1, mediates basolateral bicarbonate efflux in the
      proximal tubule by coupling the transport of 3 HCO3- to 1 Na+. The molecular
      basis underlying the different stoichiometries is not known. 2. pNBC1 and kNBC1
      are 93 % identical to each other with 41 N-terminal amino acids of kNBC1 replaced
      by 85 distinct amino acids in pNBC1. In this study we tested the hypothesis that
      the differences in stoichiometry are related to the difference between the N
      termini of the two proteins. 3. Mouse renal proximal tubule and collecting duct
      cells, deficient in both pNBC1- and kNBC1-mediated electrogenic sodium
      bicarbonate cotransport function were transfected with either pNBC1 or kNBC1.
      Cells were grown on a permeable support to confluence, mounted in an Ussing
      chamber and permeabilized apically with amphotericin B. Current through the
      cotransporter was isolated as the difference current due to the reversible
      inhibitor dinitrostilbene disulfonate. The stoichiometry was calculated from the
      reversal potential by measuring the current-voltage relationships of the
      cotransporter at different Na+ concentration gradients. 4. Our data indicate that
      both kNBC1 and pNBC1 can exhibit either a 2:1 or 3:1 stoichiometry depending on
      the cell type in which each is expressed. In proximal tubule cells, both pNBC1
      and kNBC1 exhibit a 3 HCO3-:1 Na+ stoichiometry, whereas in collecting duct
      cells, they have a 2:1 stoichiometry. These data argue against the hypothesis
      that the stoichiometric differences are related to the difference between the N
      termini of the two proteins. Moreover, the results suggest that as yet
      unidentified cellular factor(s) may modify the stoichiometry of these
      cotransporters.

PMID- 11251044
TI  - Measurement of secretory vesicle pH reveals intravesicular alkalinization by
      vesicular monoamine transporter type 2 resulting in inhibition of prohormone
      cleavage.
AB  - 1. The acidic interior of neuroendocrine secretory vesicles provides both an
      energy gradient for amine-proton exchangers (VMATs) to concentrate small
      transmitter molecules, for example catecholamines, and an optimal pH for the
      prohormone convertases which cleave hormone precursors. There is evidence that
      VMAT activity modulates prohormone cleavage, but in the absence of measurements
      of pH in secretory vesicles in intact cells, it has not been possible to
      establish whether these effects are attributable to raised intravesicular pH due
      to proton transport through VMATs. 2. Clones were generated of the hamster
      insulinoma cell line HIT-T15 expressing a pH-sensitive form of green fluorescent
      protein (GFP-F64L/S65T) targeted to secretory vesicles, with and without co
      expression of VMAT2. In order to study prohormone cleavage, further clones were
      generated that expressed preprogastrin with and without co-expression of VMAT2.
      3. Confocal microscopy of GFP fluorescence indicated that the pH in the secretory
      vesicles was 5.6 in control cells, compared with 6.6 in cells expressing VMAT2;
      the latter was reduced to 5.8 by the VMAT inhibitor reserpine. 4. Using a pulse
      chase labelling protocol, cleavage of 34-residue gastrin (G34) was found to be
      inhibited by co-expression with VMAT2, and this was reversed by reserpine.
      Similar effects on vesicle pH and G34 cleavage were produced by ammonium
      chloride. 5. We conclude that VMAT expression confers the linked abilities to
      store biogenic amines and modulate secretory vesicle pH over a range influencing
      prohormone cleavage and therefore determining the identity of regulatory peptide
      secretory products.

PMID- 11251045
TI  - Inhibition of Na+-H+ exchanger-3 interferes with apical receptor-mediated
      endocytosis via vesicle fusion.
AB  - 1. Receptor-mediated endocytosis in epithelial cells is a crucial mechanism for
      transport of macromolecules and regulation of cell-surface protein expression.
      Na+-H+ exchanger type 3 (NHE3) has been shown to cycle between the apical plasma
      membrane and the early endosomal compartment and to interfere with endocytosis.
      2. In the present study we investigated in detail the NHE3-dependent step of
      apical endocytosis in an epithelial cell line (opossum kidney cells). 3.
      Inhibition of NHE3 led to a rapid dose-dependent inhibition of apical albumin
      endocytosis but did not affect basolateral transferrin endocytosis. Re-exocytosis
      of albumin was not increased by NHE3 inhibition. 4. NHE3 dependency of albumin
      endocytosis was still observed at 20 degrees C or when microtubules had been
      disrupted. This was not the case for inhibition of vacuolar H+-ATPase. 5. NHE3
      inhibition rapidly blocked internalisation of pre-bound albumin and attenuated
      degradation of internalised albumin without changing general protein degradation.
      6. Furthermore, NHE3 inhibition reduced the rate of endocytic vesicle fusion
      significantly. 7. In summary, our data indicate that NHE3 is important for the
      early phase of the apical endocytic pathway, located between the plasma membrane
      and early endosomes, at least in part due to its involvement in endocytic vesicle
      fusion.

PMID- 11251046
TI  - Isotonic transport by the Na+-glucose cotransporter SGLT1 from humans and rabbit.
AB  - 1. In order to study its role in steady state water transport, the Na+-glucose
      cotransporter (SGLT1) was expressed in Xenopus laevis oocytes; both the human and
      the rabbit clones were tested. The transport activity was monitored as a clamp
      current and the flux of water followed optically as the change in oocyte volume.
      2. SGLT1 has two modes of water transport. First, it acts as a molecular water
      pump: for each 2 Na+ and 1 sugar molecule 264 water molecules were cotransported
      in the human SGLT1 (hSGLT1), 424 for the rabbit SGLT1 (rSGLT1). Second, it acts
      as a water channel. 3. The cotransport of water was tightly coupled to the sugar
      induced clamp current. Instantaneous changes in clamp current induced by changes
      in clamp voltage were accompanied by instantaneous changes in the rate of water
      transport. 4. The cotransported solution was predicted to be hypertonic, and an
      osmotic gradient built up across the oocyte membrane with continued transport;
      this resulted in an additional osmotic influx of water. After 5-10 min a steady
      state was achieved in which the total influx was predicted to be isotonic with
      the intracellular solution. 5. With the given expression levels, the steady state
      water transport was divided about equally between cotransport, osmosis across the
      SGLT1 and osmosis across the native oocyte membrane. 6. Coexpression of AQP1 with
      the SGLT1 increased the water permeability more than 10-fold and steady state
      isotonic transport was achieved after less than 2 s of sugar activation. One
      third of the water was cotransported, and the remainder was osmotically driven
      through the AQP1. 7. The data suggest that SGLT1 has three roles in isotonic
      water transport: it cotransports water directly, it supplies a passive pathway
      for osmotic water transport, and it generates an osmotic driving force that can
      be employed by other pathways, for example aquaporins.

PMID- 11251047
TI  - Control of rectification and permeation by two distinct sites after the second
      transmembrane region in Kir2.1 K+ channel.
AB  - 1. The rectification property of the inward rectifier K+ channel is chiefly due
      to the block of outward current by cytoplasmic Mg2+ and polyamines. In the cloned
      inward rectifier K+ channel Kir2.1 (IRK1), Asp172 in the second transmembrane
      region (M2) and Glu224 in the putative cytoplasmic region after M2 are reported
      to be critical for the sensitivity to these blockers. However, the difference in
      the inward rectification properties between Kir2.1 and a very weak inward
      rectifier sWIRK could not be explained by differences at these two sites. 2.
      Following sequence comparison of Kir2.1 and sWIRK, we focused this study on
      Glu299 located in the centre of the putative cytoplasmic region after M2. Single
      point mutants of Kir2.1 (Glu224Gly and Glu299Ser) and a double-point mutant
      (Glu224Gly-Glu299Ser) were made and expressed in Xenopus oocytes or in HEK293T
      cells. 3. Their electrophysiological properties were compared with those of wild
      type (WT) Kir2.1 and the following observations were made. (a) Glu299Ser showed a
      weaker inward rectification, a slower activation upon hyperpolarization, a slower
      decay of the outward current upon depolarization, a lower sensitivity to block by
      cytoplasmic spermine and a smaller single-channel conductance than WT. (b) The
      features of Glu224Gly were similar to those of Glu299Ser. (c) In the double
      mutant (Glu224Gly-Glu299Ser), the differences from WT described above were more
      prominent. 4. These results demonstrate that Glu299 as well as Glu224 control
      rectification and permeation, and suggest the possibility that the two sites
      contribute to the inner vestibule of the channel pore. The slowing down of the on
      and off-blocking processes by mutation of these sites implies that Glu224 and
      Glu299 function to facilitate the entry (and exit) of spermine to (and from) the
      blocking site.

PMID- 11251048
TI  - Effects of membrane potential and tension on prestin, the outer hair cell lateral
      membrane motor protein.
AB  - 1. Under whole-cell voltage clamp, the effects of initial voltage conditions and
      membrane tension on gating charge and voltage-dependent capacitance were studied
      in human embryonic kidney cells (TSA201 cell line) transiently transfected with
      the gene encoding the gerbil protein prestin. Conformational changes in this
      membrane-bound protein probably provide the molecular basis of the outer hair
      cell (OHC) voltage-driven mechanical activity, which spans the audio spectrum. 2.
      Boltzmann characteristics of the charge movement in transfected cells were
      similar to those reported for OHCs (Q(max) = 0.99 +/- 0.16 pC, z = 0.88 +/- 0.02;
      n = 5, means +/- S.E.M.). Unlike that of the adult OHC, the voltage at peak
      capacitance (V(pkcm)) was very negative (-74.7 +/- 3.8 mV). Linear capacitance in
      transfected cells was 43.7 +/- 13.8 pF and membrane resistance was 458 +/- 123
      Mohms. 3. Voltage steps from the holding potential preceding the measurement of
      capacitance-voltage functions caused a time- and voltage-dependent shift in
      V(pkcm). For a prepulse to -150 mV, from a holding potential of 0 mV, V(pkcm)
      shifted 6.4 mV, and was fitted by a single exponential time constant of 45 ms. A
      higher resolution analysis of this time course was made by measuring the change
      in capacitance during a fixed voltage step and indicated a double exponential
      shift (tau(0) = 51.6 ms, tau(1) = 8.5 s) similar to that of the native gerbil
      OHC. 4. Membrane tension, delivered by increasing pipette pressure, caused a
      positive shift in V(pkcm). A maximal shift of 7.5 mV was obtained with 2 kPa of
      pressure. The effect was reversible. 5. Our results show that the sensitivity of
      prestin to initial voltage and membrane tension, though present, is less than
      that observed in adult OHCs. It remains possible that some other interacting
      molecular species within the lateral plasma membrane of the native OHC amplifies
      the effect of tension and prior voltage on prestin's activity.

PMID- 11251049
TI  - Action of 2,3-butanedione monoxime on capacitance and electromotility of guinea
      pig cochlear outer hair cells.
AB  - 1. Whole-cell patch-clamp recordings were obtained from isolated cochlear outer
      hair cells (OHCs) while applying 2,3-butanedione monoxime (BDM) by pressure. BDM
      (5 mM) shifted the range of voltage sensitivity of membrane capacitance and cell
      length in the hyperpolarised direction by -49.6 +/- 4.0 mV (n = 12; mean +/-
      S.E.M.), without appreciable effects on membrane conductance. The shift was
      completely reversible and dose dependent, with a Hill coefficient of 1.8 /- 0.4
      and a half-maximal dose of 3.0 +/- 0.8 mM (values +/- S.D). 2. The shift of the
      capacitance curve was also reproducible in cells whose natural turgor had been
      removed. BDM had no detectable effect on the capacitance of Deiters' cells, a non
      sensory cell type of the organ of Corti. 3. The effect of BDM on membrane
      capacitance was faster than that of salicylate. At similar saturating
      concentrations (20 mM), the time constant of the capacitance changes was 1.8 +/-
      0.3 s (n = 3) for salicylate and 0.75 +/- 0.06 s (n = 3) for BDM. The recovery
      periods were 13 +/- 1 s and 1.7 +/- 0.4 s, respectively (means +/- S.E.M.). 4.
      The effect of BDM, a known inorganic phosphatase, was compared to the effects of
      okadaic acid, trifluoperazine and W-7, which are commonly used in studies of
      protein phosphorylation. Incubation of OHCs with okadaic acid (1 microM, 30-60
      min) shifted the voltage sensitivity of the membrane capacitance in the
      hyperpolarised direction. Incubation with trifluoperazine (30 microM) and W-7
      (150 microM) shifted it in the opposite, depolarised direction. BDM induced
      hyperpolarising shifts even in the presence of W-7. 5. Simultaneous measurement
      of membrane capacitance and intracellular free Ca2+ concentration ([Ca2+]i)
      showed that BDM action on OHC voltage-dependent capacitance and electromotility
      is not mediated by changes of [Ca2+]i. 6. Our results suggest that: (a) the
      effects of BDM are unrelated to its inorganic phosphatase properties, cell turgor
      conditions or Ca2+ release from intracellular stores; and (b) BDM may target
      directly the voltage sensor of the OHC membrane motor protein.

PMID- 11251050
TI  - Phasic mechanoreceptor stimuli can induce phasic activation of upper airway
      muscles in humans.
AB  - 1. Upper airway dilator muscles are phasically activated throughout breathing by
      respiratory pattern generator neurons. Studies have shown that non-physiological
      upper airway mechanoreceptive stimuli (e.g. rapidly imposed pulses of negative
      pressure) also activate these muscles. Such reflexes may become activated during
      conditions that alter airway resistance in order to stabilise airway patency. 2.
      To determine the contribution of ongoing mechanoreceptive reflexes to phasic
      activity of airway dilators, we assessed genioglossal electromyogram (GG EMG:
      rectified with moving time average of 100 ms) during slow (physiological)
      oscillations in negative pressure generated spontaneously and passively (negative
      pressure ventilator). 3. Nineteen healthy adults were studied while awake, during
      passive mechanical ventilation across normal physiological ranges of breathing
      rates (13-19 breaths min-1) and volumes (0.5-1.0 l) and during spontaneous
      breathing across the physiological range of end-tidal carbon dioxide (PET,CO2; 32
      45 mmHg). 4. Within-breath phasic changes in airway mechanoreceptor stimuli
      (negative pressure or flow) were highly correlated with within-breath phasic
      genioglossal activation, probably representing a robust mechanoreceptive reflex.
      These reflex relationships were largely unchanged by alterations in central drive
      to respiratory pump muscles or the rate of mechanical ventilation within the
      ranges studied. A multivariate model revealed that tonic GG EMG, PET,CO2 and
      breath duration provided no significant independent information in the prediction
      of inspiratory peak GG EMG beyond that provided by epiglottic pressure, which
      alone explained 93 % of the variation in peak GG EMG across all conditions. The
      overall relationship was: Peak GG EMG = 79.7 - (11.3 X Peak epiglottic pressure),
      where GG EMG is measured as percentage of baseline, and epiglottic pressure is in
      cmH2O. 5. These data provide strong evidence that upper airway dilator muscles
      can be activated throughout inspiration via ongoing mechanoreceptor reflexes.
      Such a feedback mechanism is likely to be active on a within-breath basis to
      protect upper airway patency in awake humans. This mechanism could mediate the
      increased genioglossal activity observed in patients with obstructive sleep
      apnoea (i.e. reflex compensation for an anatomically smaller airway).

PMID- 11251051
TI  - Purinergic control of intercellular communication between Hensen's cells of the
      guinea-pig cochlea.
AB  - 1. Hensen's cells in the isolated cochlea were stimulated by extracellular
      adenosine 5'-triphosphate (ATP) applied to their endolymphatic surface while
      changes in membrane current and intracellular calcium concentration ([Ca2+]i)
      were measured simultaneously. The response consisted of (i) an initial rapid
      inward current accompanied by elevation of the [Ca2+]i, (ii) a more slowly rising
      inward current accompanied by a rise of the [Ca2+]i and (iii) a slowly developing
      reduction of input conductance. 2. The slower responses were maintained in the
      absence of extracellular Ca2+. Similar responses were produced by increasing the
      [Ca2+]i via UV flash photolysis of intracellular D-myo-inositol 1,4,5
      trisphosphate, P4(5)-(1-(2-nitrophenyl)ethyl) ester (caged InsP3) loaded at
      pipette concentrations of 8-16 microM. 3. The slow inward current, reversing
      around 0 mV, was blocked by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid
      (DIDS). 4. Bath application of U-73122 (1 microM), a phospholipase C inhibitor,
      eliminated the slow Ca2+-release component of the response to ATP. It is proposed
      that the effects of ATP are mediated by the co-activation of ionotropic P2X and
      metabotropic P2Y receptors. 5. Immunohistochemistry using light and electron
      microscopy revealed that inositol 1,4,5-trisphosphate (InsP3) receptors delineate
      a network within the cells. 6. The coupling ratio (CR) between cell pairs
      measured in dual patch-clamp recordings was 0.356 +/- 0.024. The coupling
      reversibly decreased to 51 % of the control within 2 min of applying 100 microM
      ATP. Flash photolysis of 32 microM intracellular caged InsP3 and 1 mM caged Ca2+
      reduced CR to 42 and 62 % of the control, respectively. 7. We propose that
      endolymphatic ATP via P2X and P2Y receptors can control intercellular
      communication amongst Hensen's cells by reducing gap junction conductance in a
      Ca2+- and InsP3-dependent manner.

PMID- 11251052
TI  - Simultaneous measurements of changes in sarcoplasmic reticulum and cytosolic.
AB  - 1. The role of the sarcoplasmic reticulum (SR) was investigated in spontaneous
      and agonist-induced uterine Ca2+ transients, by combining low- (mag-fluo-4) and
      high-affinity (fura-2) indicators to measure intraluminal SR ([Ca2+]L) and
      cytosolic ([Ca2+]i) calcium concentration, simultaneously, in single smooth
      muscle cells from pregnant rat uterus. 2. Carbachol or ATP, in the absence of
      extracellular Ca2+, decreased [Ca2+]L and increased [Ca2+]i. Although some
      replenishment (around 50 %) occurred in its absence, extracellular Ca2+ was
      required for full replenishment of the SR Ca2+. 3. In 4/15 cells, ATP evoked
      oscillations of [Ca2+]i. These were accompanied by successive release and re
      uptake of SR Ca2+. Inhibition of the SR Ca2+-ATPase with thapsigargin abolished
      the oscillations and luminal changes. 4. Spontaneous [Ca2+]i transients produced
      no detectable changes in [Ca2+]L. The larger [Ca2+]i transients evoked by high-K+
      depolarisation increased [Ca2+]L. Spontaneous activity was inhibited when [Ca2+]L
      was increased. 5. These data show that it is possible to simultaneously measure
      SR and cytosolic [Ca2+], and to investigate their response to agonist application
      and spontaneous activity.

PMID- 11251053
TI  - Different Ca2+ releasing action of caffeine and depolarisation in skeletal muscle
      fibres of the rat.
AB  - 1. The relative abilities of caffeine and transverse tubular (T-) system
      depolarisation to induce Ca2+ release in mammalian skeletal muscle were compared
      in mechanically skinned fibres of the rat, in order to determine whether normal
      excitation-contraction (E-C) coupling is achieved by up-regulating the Ca2+
      induced Ca2+ release process, as caffeine is known to do. 2. Caffeine triggered
      Ca2+ release in soleus (slow-twitch) fibres at much lower concentrations than in
      extensor digitorum longus (EDL) (fast-twitch) fibres when the sarcoplasmic
      reticulum (SR) of each type was loaded with Ca2+ at close to endogenous levels.
      The difference in caffeine sensitivity resulted at least in part from the SR
      being loaded endogenously at near maximal capacity in soleus fibres but at less
      than half of maximal capacity in EDL fibres. The caffeine sensitivity could be
      reversed by reversing the relative level of SR loading. 3. The ability of
      caffeine to induce Ca2+ release was markedly reduced by lowering the level of SR
      loading or by raising the free [Mg2+] from 1 to 3 mM. Caffeine, even at 30 mM,
      triggered little or no Ca2+ release in EDL fibres (a) at 1 mM (physiological)
      Mg2+ when the SR was loaded at two-thirds or less of the endogenous level, and
      (b) at 3 mM Mg2+ when the SR was loaded at close to the endogenous level. In
      contrast, depolarisation potently elicited Ca2+ release under these conditions in
      the same fibres. 4. The inability of 30 mM caffeine to induce Ca2+ release under
      certain conditions was not attributable to desensitisation or inactivation of the
      release channels, because there was no response even upon initial exposure to
      caffeine and depolarisation always remained able to trigger Ca2+ release. It
      instead appeared that caffeine was a relatively ineffectual stimulus in EDL
      fibres except under conditions where (a) the SR was heavily loaded, (b) the free
      [Mg2+] was low, or (c) a high [Cl-] was present. 5. These results show that the
      normal E-C coupling mechanism in mammalian skeletal muscle does not involve just
      enhancing Ca2+-induced Ca2+ release, and evidently requires the removal or
      bypassing of the inhibitory effect of Mg2+ on the Ca2+ release channels.

PMID- 11251054
TI  - Interdependent effects of inorganic phosphate and creatine phosphate on
      sarcoplasmic reticulum Ca2+ regulation in mechanically skinned rat skeletal
      muscle.
AB  - 1. The effects of creatine phosphate (CP) and inorganic phosphate (Pi) on
      sarcoplasmic reticulum (SR) Ca2+ regulation were investigated in mechanically
      skinned muscle fibres from rat extensor digitorum longus (EDL) muscles. Changes
      in [Ca2+] were detected using fura-2 fluorescence, during continuous perfusion or
      when the solution surrounding the preparation was restricted to approximately 6
      microl by stopping perfusion. 2. In solutions with 5 mM ATP and 10 mM CP,
      stopping the flow for 2-3 min had no effect on [Ca2+] within the bath. This
      suggests that SR Ca2+ uptake is balanced by an efflux under these conditions. 3.
      In solutions with CP, the introduction of Pi induced a small transient rise in
      [Ca2+], due to Ca2+ loss from the SR. Following equilibration with solutions
      containing Pi (> or = 5 mM), a maintained decrease in [Ca2+] occurred when the
      flow was stopped. This is consistent with calcium phosphate (Ca-Pi) precipitation
      within the SR, resulting in maintained Ca2+ uptake. 4. In the absence of CP, the
      [Ca2+] within the bath increased progressively when the flow was stopped. This
      rise in [Ca2+] was inhibited by an alternative ATP regenerating system comprising
      phosphoenolpyruvate (PEP) and pyruvate kinase (PK). Therefore, the loss of Ca2+
      from the SR may result from local ADP accumulation and the consequent reversal of
      the SR Ca2+ pump. 5. In the absence of CP, the initial Ca2+ release associated
      with the introduction of Pi increased markedly. Following prolonged equilibration
      with solutions containing Pi, a rise in [Ca2+] occurred within the bath when the
      flow was stopped. Maintained Ca2+ uptake associated with Ca-Pi precipitation was
      not apparent at any level of Pi tested (1-60 mM), when CP was absent. 6. These
      results suggest that withdrawal of CP is associated with activation of a SR Ca2+
      efflux pathway. This may involve reversal of the SR Ca2+ pump, due to local ADP
      accumulation. In the absence of CP, the dominant influence of Pi appears to
      involve further Ca2+ efflux via the SR Ca2+ pump. The possible relevance of these
      effects to skeletal muscle fatigue is considered.

PMID- 11251055
TI  - Extracellular carbonic anhydrase activity facilitates lactic acid transport in
      rat skeletal muscle fibres.
AB  - 1. In skeletal muscle an extracellular sarcolemmal carbonic anhydrase (CA) has
      been demonstrated. We speculate that this CA accelerates the interstitial
      CO2/HCO3- buffer system so that H+ ions can be rapidly delivered or buffered in
      the interstitial fluid. Because > 80 % of the lactate which crosses the
      sarcolemmal membrane is transported by the H+-lactate cotransporter, we examined
      the contributions of extracellular and intracellular CA to lactic acid transport,
      using ion-selective microelectrodes for measurements of intracellular pH (pHi)
      and fibre surface pH (pHs) in rat extensor digitorum longus (EDL) and soleus
      fibres. 2. Muscle fibres were exposed to 20 mM sodium lactate in the absence and
      presence of the CA inhibitors benzolamide (BZ), acetazolamide (AZ), chlorzolamide
      (CZ) and ethoxzolamide (EZ). The initial slopes (dpHs/dt, dpHi/dt) and the
      amplitudes (DeltapHs, DeltapHi) of pH changes were quantified. From dpHi/dt,
      DeltapHi and the total buffer factor (BFtot) the lactate fluxes (mM min-1) and
      intracellular lactate concentrations ([lactate]i) were estimated. 3. BFtot was
      obtained as the sum of the non-HCO3- buffer factor (BFnon-HCO3) and the HCO3-
      buffer factor (BFHCO3). BFnon-HCO3 was 35 +/- 4 mM pH-1 for the EDL (n = 14) and
      86 /- 16 mM pH-1 for the soleus (n = 14). 4. In soleus, 10 mM cinnamate inhibited
      lactate influx by 44 % and efflux by 30 %; in EDL, it inhibited lactate influx by
      37 % and efflux by 20 %. Cinnamate decreased [lactate]i, in soleus by 36 % and in
      EDL by 45 %. In soleus, 1 mM DIDS reduced lactate influx by 18 % and efflux by 16
      %. In EDL, DIDS lowered the influx by 27 % but had almost no effect on efflux.
      DIDS reduced [lactate]i by 20 % in soleus and by 26 % in EDL. 5. BZ (0.01 mM) and
      AZ (0.1 mM), which inhibit only the extracellular sarcolemmal CA, led to a
      significant increase in dpHs/dt and pHs by about 40 %-150 % in soleus and EDL. BZ
      and AZ inhibited the influx and efflux of lactate by 25 %-50 % and reduced
      [lactate]i by about 40 %. The membrane-permeable CA inhibitors CZ (0.5 mM) and EZ
      (0.1 mM), which inhibit the extracellular as well as the intracellular CAs,
      exerted no greater effects than the poorly permeable inhibitors BZ and AZ did. 6.
      In soleus, 10 mM cinnamate inhibited the lactate influx by 47 %. Addition of 0.01
      mM BZ led to a further inhibition by only 10 %. BZ alone reduced the influx by 37
      %. 7. BZ (0.01 mM) had no influence on the Km value of the lactate transport, but
      led to a decrease in maximal transport rate (Vmax). In EDL, BZ reduced Vmax by 50
      % and in soleus by about 25 %. 8. We conclude that the extracellular sarcolemmal
      CA plays an important role in lactic acid transport, while internal CA has no
      effect, a difference most likely attributable to the high internal vs. low
      extracellular BF(non-HCO3). The fact that the effects of cinnamate and BZ are not
      additive indicates that the two inhibitors act at distinct sites on the same
      transport pathway for lactic acid.

PMID- 11251056
TI  - Glycogen synthase localization and activity in rat skeletal muscle is strongly
      dependent on glycogen content.
AB  - 1. The influence of muscle glycogen content on glycogen synthase (GS)
      localization and GS activity was investigated in skeletal muscle from male Wistar
      rats. 2. Two groups of rats were obtained, preconditioned with a combination of
      exercise and diet to obtain either high (HG) or low (LG) muscle glycogen content.
      The cellular distribution of GS was studied using subcellular fractionation and
      confocal microscopy of immunostained single muscle fibres. Stimulation of GS
      activity in HG and LG muscle was obtained with insulin or contractions in the
      perfused rat hindlimb model. 3. We demonstrate that GS translocates from a
      glycogen-enriched membrane fraction to a cytoskeleton fraction when glycogen
      levels are decreased. Confocal microscopy supports the biochemical observations
      that the subcellular localization of GS is influenced by muscle glycogen content.
      GS was not found in the nucleus. 4. Investigation of the effect of glycogen
      content on GS activity in basal and insulin- and contraction-stimulated muscle
      shows that glycogen has a strong inhibitory effect on GS activity. Our data
      demonstrate that glycogen is a more potent regulator of glycogen synthase
      activity than insulin. Furthermore we show that the contraction-induced increase
      in GS activity is merely a result of a decrease in muscle glycogen content. 5. In
      conclusion, the present study shows that GS localization is influenced by muscle
      glycogen content and that not only basal but also insulin- and contraction
      stimulated GS activity is strongly regulated by glycogen content in skeletal
      muscle.

PMID- 11251057
TI  - Effects of sarcomere length and temperature on the rate of ATP utilisation by
      rabbit psoas muscle fibres.
AB  - 1. The steady state rate of ATP utilisation by single permeabilised fibres from
      rabbit psoas muscle immersed in silicone oil was measured using a linked enzyme
      assay that coupled ADP production to the oxidation of NADH.2. At sarcomere length
      2.5 microm, at 10 degrees C, the rate of ATP utilisation in relaxing conditions
      was 6 +/- 1 microM s-1 (mean +/- S.E.M., n = 8 fibres); during isometric
      contraction it was 310 +/- 10 microM s-1 (mean +/- S.E.M., n = 11). Assuming a
      myosin active site concentration of 150 microM, these values correspond to rates
      of ATP utilisation per active site of about 0.04 and 2.1 s-1, respectively. 3.
      The rate of ATP utilisation in relaxing conditions was independent of sarcomere
      length in the range 2.5-4.0 microm. The rate of ATP utilisation during isometric
      contraction had a dependence on resting sarcomere length similar to that of
      isometric force in the range 2.5-4.0 microm, but was less strongly dependent on
      sarcomere length than was isometric force in the range 1.5-2.5 microm. 4. The
      rate of ATP utilisation in relaxing conditions had a Q10 of 2.5 in the
      temperature range 7-25 degrees C, but this increased to 9.7 in the range 25-35
      degrees C, suggesting that some active force may have been generated in relaxing
      solution at temperatures above 25 degrees C. 5. The rate of ATP utilisation
      during isometric contraction had a Q10 of 3.6 throughout the temperature range 7
      25 degrees C; this was similar to the Q10 for isometric force at low temperature
      (3.5 at 7-10 degrees C) but much larger than that for isometric force at higher
      temperature (1.3 at 20-25 degrees C). 6. Application of the NADH-linked assay to
      single muscle fibres in oil improves the effective sensitivity and time
      resolution of the method, and allows continuous measurements of the rate of ADP
      production during active contraction.

PMID- 11251058
TI  - Effect of active shortening on the rate of ATP utilisation by rabbit psoas muscle
      fibres.
AB  - 1. The rate of ATP utilisation during active shortening of single skinned fibres
      from rabbit psoas muscle at 10 degrees C was measured using an NADH-linked assay.
      Fibres were immersed in silicone oil and illuminated with 365 nm light. The
      amounts of NADH and carboxytetramethylrhodamine (CTMR) in the illuminated region
      of the fibre were measured simultaneously from fluorescence emission at 425-475
      and 570-650 nm, respectively. The ratio of these two signals was used to
      determine the intracellular concentration of NADH, and thus the ATP utilisation,
      without interference from movements of the fibre with respect to the measuring
      light beam. 2. The total extra ATP utilisation due to shortening (ATP) was
      determined by extrapolation of the steady isometric rates before and after
      shortening to the mid-point of the shortening period. ATP had a roughly linear
      dependence on the extent of shortening in the range 1-15 % fibre length (L0) at a
      shortening velocity of 0.4 L0 s-1 from initial sarcomere length 2.7 microm. For
      shortening of 1 % L0, ATP was 21 +/- 1 M (mean +/- S.E.M., n = 3). 3. The mean
      rate of ATP utilisation during ramp shortening of 10 % L0 had a roughly linear
      dependence on shortening velocity in the range 0.05-1.2 L0 s-1. During unloaded
      shortening at 1.2 L0 s-1 the mean rate of ATP utilisation was 1.7 mM s-1, about 9
      times the isometric rate. ATP was roughly independent of shortening velocity, and
      was 84 +/- 9 microM (mean +/- S.E.M., n = 6) for shortening of 10 % L0. 4. The
      implications of these results for mechanical-chemical coupling in muscle are
      discussed. The total ATP utilisation associated with shortening of 1 % L0 is only
      about 17 % of the concentration of the myosin heads in the fibre, suggesting that
      during isometric contraction either less than 17 % of the myosin heads are
      attached to actin, or that heads can detach without commitment to ATP splitting.
      The fraction of myosin heads attached to actin during unloaded shortening is
      estimated from the rate of ATP utilisation to be less than 7 %.

PMID- 11251059
TI  - Quantitative evaluation of mitochondrial calcium content in rat cortical neurones
      following a glutamate stimulus.
AB  - 1. Recent observations showed that a mitochondrial Ca2+ increase is necessary for
      an NMDA receptor stimulus to be toxic to cortical neurones. In an attempt to
      determine the magnitude of the Ca2+ fluxes involved in this phenomenon, we used
      carbonylcyanide-p-(trifluoromethoxy)phenylhydrazone (FCCP), a mitochondrial
      proton gradient uncoupler, to release mitochondrial free calcium ([Ca2+]m) during
      and following a glutamate stimulus, and magfura-2 to monitor cytoplasmic free
      calcium ([Ca2+]c). 2. FCCP treatment of previously unstimulated neurones barely
      changed [Ca2+]c whereas when added after a glutamate stimulus it elevated [Ca2+]c
      to a much greater extent than did exposure to glutamate, suggesting a very large
      accumulation of Ca2+ in the mitochondria. 3. Mitochondrial Ca2+ uptake was
      dependent on glutamate concentration, whereas the changes in the overall quantity
      of Ca2+ entering the cell, obtained by simultaneously treating neurones with
      glutamate and FCCP, showed a response that was essentially all-or-none. 4.
      Mitochondrial Ca2+ uptake was also dependent on the nature and duration of a
      given stimulus as shown by comparing [Ca2+]m associated with depolarization and
      treatment with kainate, NMDA or glutamate. Large mitochondrial Ca2+ accumulation
      only occurred after a glutamate or NMDA stimulus. 5. These studies provide a
      method of estimating the accumulation of Ca2+ in the mitochondria of neurones,
      and suggest that millimolar concentrations of Ca2+ may be reached following
      intense glutamate stimulation. It was shown that substantially more Ca2+ enters
      neurones following glutamate receptor activation than is reflected by [Ca2+]c
      increases.

PMID- 11251060
TI  - Transmitter release modulation by intracellular Ca2+ buffers in facilitating and
      depressing nerve terminals of pyramidal cells in layer 2/3 of the rat neocortex
      indicates a target cell-specific difference in presynaptic calcium dynamics.
AB  - 1. In connections formed by nerve terminals of layer 2/3 pyramidal cells onto
      bitufted interneurones in young (postnatal day (P)14-15) rat somatosensory
      cortex, the efficacy and reliability of synaptic transmission were low. At these
      connections release was facilitated by paired-pulse stimulation (at 10 Hz). In
      connections formed by terminals of layer 2/3 pyramids with multipolar
      interneurones efficacy and reliability were high and release was depressed by
      paired-pulse stimulation. In both types of terminal, however, the voltage
      dependent Ca2+ channels that controlled transmitter release were predominantly of
      the P/Q- and N-subtypes. 2. The relationship between unitary EPSP amplitude and
      extracellular calcium concentration ([Ca2+]o) was steeper for facilitating than
      for depressing terminals. Fits to a Hill equation with nH = 4 indicated that the
      apparent KD of the Ca2+ sensor for vesicle release was two- to threefold lower in
      depressing terminals than in facilitating ones. 3. Intracellular loading of
      pyramidal neurones with the fast and slowly acting Ca2+ buffers BAPTA and EGTA
      differentially reduced transmitter release in these two types of terminal.
      Unitary EPSPs evoked by pyramidal cell stimulation in bitufted cells were reduced
      by presynaptic BAPTA and EGTA with half-effective concentrations of approximately
      0.1 and approximately 1 mM, respectively. Unitary EPSPs evoked in multipolar
      cells were reduced to one-half of control at higher concentrations of presynaptic
      BAPTA and EGTA (approximately 0.5 and approximately 7 mM, respectively). 4.
      Frequency-dependent facilitation of EPSPs in bitufted cells was abolished by EGTA
      at concentrations of > or = 0.2 mM, suggesting that accumulation of free Ca2+ is
      essential for facilitation in the terminals contacting bitufted cells. In
      contrast, facilitation was unaffected or even slightly increased in the terminals
      loaded with BAPTA in the concentration range 0.02-0.5 mM. This is attributed to
      partial saturation of exogenously added BAPTA. However, BAPTA at concentrations >
      or = 1 mM also abolished facilitation. 5. Frequency-dependent depression of EPSPs
      in multipolar cells was not significantly reduced by EGTA. With BAPTA, the
      depression decreased at concentrations > 0.5 mM, concomitant with a reduction in
      amplitude of the first EPSP in a train. 6. An analysis is presented that
      interprets the effects of EGTA and BAPTA on synaptic efficacy and its short-term
      modification during paired-pulse stimulation in terms of changes in [Ca2+] at the
      release site ([Ca2+]RS) and that infers the affinity of the Ca2+ sensor from the
      dependence of unitary EPSPs on [Ca2+]o. 7. The results suggest that the target
      cell-specific difference in release from the terminals on bitufted or multipolar
      cells can be explained by a longer diffusional distance between Ca2+ channels and
      release sites and/or lower Ca2+ channels density in the terminals that contact
      bitufted cells. This would lead to a lower [Ca2+] at release sites and would also
      explain the higher apparent K(D) of the Ca2+ sensor in facilitating terminals.

PMID- 11251061
TI  - Selective knockout of intramuscular interstitial cells reveals their role in the
      generation of slow waves in mouse stomach.
AB  - 1. Intracellular recording techniques were used to compare the patterns of
      electrical activity generated in the antral region of the stomachs of wild-type
      and W/W(V) mutant mice. Immunohistochemical techniques were used to determine the
      distribution of c-kit-positive interstitial cells of Cajal (ICC) within the same
      region of the stomach. 2. In wild-type mice interstitial cells were found at the
      level of the myenteric plexus (ICC(MY)) and distributed within the smooth muscle
      bundles (ICC(IM)). In these preparations slow waves, which consisted of initial
      and secondary components, were detected. 3. In W/WV mutant mice ICC(MY) could be
      identified at the level of the myenteric plexus but ICC(IM) were not detected
      within smooth muscle bundles. Intracellular recordings revealed that smooth
      muscle cells generated waves of depolarization; these lacked a secondary
      component. 4. These results indicate that the secondary regenerative component of
      a slow wave is generated by ICC(IM). Thus the depolarization arising from the
      pacemaker cells, ICC(MY), is augmented by ICC(IM), so causing a substantial
      membrane depolarization in the circular muscle layer. Rather than contributing
      directly to rhythmical electrical activity, smooth muscle cells appear to
      depolarize at the command of the two subpopulations of ICC.

PMID- 11251062
TI  - Differential changes in insulin-like growth factors and their binding proteins
      following asphyxia in the preterm fetal sheep.
AB  - 1. The purpose of this study was to examine the changes in circulating
      concentrations of insulin-like growth factor (IGF)-I, IGF-II, IGF-binding protein
      (IGFBP)-1, IGFBP-2 and insulin following asphyxia in utero. 2. Fetal sheep at 90
      93 days gestation underwent either sham occlusion (n = 7) or asphyxia (n = 6)
      induced by complete umbilical cord occlusion for 30 min. Fetal blood samples were
      taken before occlusion and 4, 6, 24, 48 and 72 h post-occlusion. 3. During the
      early phase of recovery there was a substantial fall (80 %) in circulating plasma
      IGF-I concentrations by 6 h post-asphyxia (P < 0.001). This was associated with a
      rapid rise in IGFBP-1 (P < 0.001), but no change in IGF-II or IGFBP-2. Insulin
      was significantly reduced at 4 h (P < 0.001) and glucose slightly elevated (P <
      0.05), but insulin values returned to baseline by 6 h. Between 24 and 72 h of
      recovery, IGF-I gradually increased, IGFBP-1 returned to control values, and
      there was an increase in IGFBP-2 after 24 h (P < 0.05) and in IGF-II by 72 h (P <
      0.05) after asphyxia. 4. These data demonstrate a differential effect of asphyxia
      on the IGF axis of the premature fetal sheep. A key finding was the large fall in
      circulating IGF-I, but not IGF-II, during the early phase of recovery. IGF-I
      bioavailability was, in part, regulated by IGFBP-1, but maximal changes in IGF-I
      and IGFBP-1 were independent of plasma insulin and glucose.5. The impact of this
      substantial change in circulating IGF-I on the fetus is unknown. It may
      facilitate metabolic requirements by promoting catabolism. Alternatively, as IGFs
      play a role in wound repair, the acute changes in IGF-I and IGFBP-1 may reflect
      transport of IGF-I from the circulatory pool to injured tissues to promote wound
      repair.

PMID- 11251063
TI  - Characteristics of arterial wall shear stress which cause endothelium-dependent
      vasodilatation in the anaesthetized dog.
AB  - 1. The effects of changes in the mean and amplitude of arterial wall shear stress
      on endothelium-dependent arterial dilatation of the iliac artery of the
      anaesthetized dog were examined. 2. Changes in the mean and amplitude of blood
      flow and wall shear stress were brought about by varying local peripheral
      resistance and stroke volume using a distal infusion of acetylcholine and the
      stimulation of the left ansa subclavia. Changes in the diameter of a segment of
      the iliac artery with the endothelium intact, relative to a segment with no
      endothelium, were used as an index of the release of nitric oxide. 3. The
      increase in mean blood flow was from 84 +/- 12 to 527 +/- 53 ml min-1 and in
      amplitude was from 365 +/- 18 to 695 +/- 38 ml min-1 (means +/- S.E.M.). The
      increase in mean wall shear stress was from 1.78 +/- 0.30 to 7.66 +/- 1.01 N m-2
      and in amplitude was from 7.37 +/- 0.46 to 13.9 +/- 2.00 N m-2 (means +/-
      S.E.M.). 4. Increases in mean shear stress caused an increase in the diameter
      only of the section of artery with endothelium; the slope of the relationship was
      0.064 +/- 0.006 mm N-1 m2 (mean +/- S.E.M., P < 0.001); changes in the amplitude
      of shear stress did not cause an increase in diameter. Changes in both the mean
      and amplitude of shear stress had no significant effect on the diameter of the
      section of artery with no endothelium. 5. These findings coupled with the known
      anti-atheroma effects of nitric oxide and the effect of shear stress on cell
      adhesion and platelet aggregation offer a possible explanation for the
      disposition of atheroma in those parts of the arterial system which have low mean
      and high amplitude of wall shear stress.

PMID- 11251064
TI  - Interhemispheric facilitation of the hand motor area in humans.
AB  - 1. We investigated interhemispheric interactions between the human hand motor
      areas using transcranial cortical magnetic and electrical stimulation. 2. A
      magnetic test stimulus was applied over the motor cortex contralateral to the
      recorded muscle (test motor cortex), and an electrical or magnetic conditioning
      stimulus was applied over the ipsilateral hemisphere (conditioning motor cortex).
      We investigated the effects of the conditioning stimulus on responses to the test
      stimulus. 3. Two effects were elicited at different interstimulus intervals
      (ISIs): early facilitation (ISI = 4-5 ms) and late inhibition (ISI > or = 11 ms).
      4. The early facilitation was evoked by a magnetic or anodal electrical
      conditioning stimulus over the motor point in the conditioning hemisphere, which
      suggests that the conditioning stimulus for early facilitation directly activates
      corticospinal neurones. 5. The ISIs for early facilitation taken together with
      the time required for activation of corticospinal neurones by I3-waves in the
      test hemisphere are compatible with the interhemispheric conduction time through
      the corpus callosum. Early facilitation was observed in responses to I3-waves,
      but not in responses to D-waves nor to I1-waves. Based on these results, we
      conclude that early facilitation is mediated through the corpus callosum. 6. If
      the magnetic conditioning stimulus induced posteriorly directed currents, or if
      an anodal electrical conditioning stimulus was applied over a point 2 cm anterior
      to the motor point, then we observed late inhibition with no early facilitation.
      7. Late inhibition was evoked in responses to both I1- and I3-waves, but was not
      evoked in responses to D-waves. The stronger the conditioning stimulus was, the
      greater was the amount of inhibition. These results are compatible with surround
      inhibition at the motor cortex.

PMID- 11251065
TI  - Two sites for modulation of human sympathetic activity by arterial baroreceptors?
AB  - 1. Peroneal muscle sympathetic nerve activity (MSA), finger blood pressure and
      cardiac intervals were recorded at rest in 60 healthy subjects, aged 18-71 years.
      Arterial baroreflex control of MSA was analysed by relating each spontaneous
      sympathetic burst to the diastolic blood pressure and the cardiac interval of the
      heart beat during which the burst was generated. The results were expressed as
      blood pressure/cardiac interval threshold for occurrence of bursts, and as
      baroreflex sensitivity (i.e. the relationship between diastolic pressure/cardiac
      interval and burst strength). 2. Significant blood pressure/cardiac interval
      thresholds were present in all subjects and old subjects had less variability of
      thresholds than young subjects. In contrast, significant baroreflex sensitivity
      for diastolic pressure and cardiac interval was present in only 55 and 73 % of
      the subjects, respectively. There was no age-related difference in sensitivity.
      3. In 40 subjects, two 5 min periods from the same recording were analysed. The
      number of sympathetic bursts and the threshold for occurrence of bursts were
      reproducible in all subjects. In contrast, significant baroreflex sensitivity in
      both periods was present in only 30 % (diastolic pressure) and 40 % (cardiac
      interval) of the subjects. 4. The results show that the baroreflex mechanisms
      regulating the occurrence and strength of sympathetic bursts are not identical.
      We suggest that the modulation occurs at two sites, one which determines whether
      or not a burst will occur, and another at which the strength of the discharge is
      determined.

PMID- 11251066
TI  - Sarcoplasmic reticulum function and muscle contractile character following
      fatiguing exercise in humans.
AB  - 1. This study examined the alterations in calcium release, calcium uptake and
      calcium ATPase activity of skeletal muscle sarcoplasmic reticulum in response to
      a bout of intense dynamic knee extensor exercise, and the relationship between
      these changes and alterations in muscle contractile characteristics in the human
      quadriceps. 2. In biopsy samples taken from the vastus lateralis, sarcoplasmic
      reticulum calcium release and calcium uptake were significantly depressed (P <
      0.01 and 0.05, respectively) immediately following the exercise with no
      alteration in the sarcoplasmic reticulum Ca2+-ATPase activity. 3. A 33 %
      reduction in the maximum voluntary isometric torque was found following the
      exercise, with reduced torques from electrically evoked isometric contractions at
      low frequencies of stimulation (10 and 20 Hz) but not at higher frequencies (50
      and 100 Hz). 4. The depressed calcium release was correlated (P < 0.05) with a
      decreased ratio of torques generated at 20:50 Hz, indicating an involvement in
      low frequency fatigue; however, no correlations between the muscle relaxation
      times or rates of change of torque and calcium uptake were observed.

PMID- 11251067
TI  - Phosphatidylcholine synthesis influences the diacylglycerol homeostasis required
      for SEC14p-dependent Golgi function and cell growth.
AB  - Phosphatidylcholine and phosphatidylethanolamine are the most abundant
      phospholipids in eukaryotic cells and thus have major roles in the formation and
      maintenance of vesicular membranes. In yeast, diacylglycerol accepts a
      phosphocholine moiety through a CPT1-derived cholinephosphotransferase activity
      to directly synthesize phosphatidylcholine. EPT1-derived activity can transfer
      either phosphocholine or phosphoethanolamine to diacylglcyerol in vitro, but is
      currently believed to primarily synthesize phosphatidylethanolamine in vivo. In
      this study we report that CPT1- and EPT1-derived cholinephosphotransferase
      activities can significantly overlap in vivo such that EPT1 can contribute to 60%
      of net phosphatidylcholine synthesis via the Kennedy pathway. Alterations in the
      level of diacylglycerol consumption through alterations in phosphatidylcholine
      synthesis directly correlated with the level of SEC14-dependent invertase
      secretion and affected cell viability. Administration of synthetic di8:0
      diacylglycerol resulted in a partial rescue of cells from SEC14-mediated cell
      death. The addition of di8:0 diacylglycerol increased di8:0 diacylglycerol levels
      20-40-fold over endogenous long-chain diacylglycerol levels. Di8:0 diacylglcyerol
      did not alter endogenous phospholipid metabolic pathways, nor was it converted to
      di8:0 phosphatidic acid.

PMID- 11251068
TI  - Selective formation of Sed5p-containing SNARE complexes is mediated by
      combinatorial binding interactions.
AB  - Sed5p is the only syntaxin family member required for protein transport through
      the yeast Golgi and it is known to bind up to nine other soluble N-ethylmaleimide
      sensitive factor attachment receptor (SNARE) proteins in vivo. We describe in
      vitro binding experiments in which we identify ternary and quaternary Sed5p
      containing SNARE complexes. The formation of SNARE complexes among these
      endoplasmic reticulum- and Golgi-localized proteins requires Sed5p and is
      syntaxin-selective. In addition, Sed5p-containing SNARE complexes form
      selectively and this selectivity is mediated by Sed5p-containing intermediates
      that discriminate among subsequent binding partners. Although many of these
      SNAREs have overlapping distributions in vivo, the SNAREs that form complexes
      with Sed5p in vitro reflect their functionally distinct locales. Although SNARE
      SNARE interactions are promiscuous and a single SNARE protein is often found in
      more than one complex, both the biochemical as well as genetic analyses reported
      here suggest that this is not a result of nonselective direct substitution of one
      SNARE for another. Rather our data are consistent with the existence of multiple
      (perhaps parallel) trafficking pathways where Sed5p-containing SNARE complexes
      play overlapping and/or distinct functional roles.

PMID- 11251069
TI  - The nuclear export receptor Xpo1p forms distinct complexes with NES transport
      substrates and the yeast Ran binding protein 1 (Yrb1p).
AB  - Xpo1p (Crm1p) is the nuclear export receptor for proteins containing a leucine
      rich nuclear export signal (NES). Xpo1p, the NES-containing protein, and GTP
      bound Ran form a complex in the nucleus that translocates across the nuclear
      pore. We have identified Yrb1p as the major Xpo1p-binding protein in
      Saccharomyces cerevisiae extracts in the presence of GTP-bound Gsp1p (yeast Ran).
      Yrb1p is cytoplasmic at steady-state but shuttles continuously between the
      cytoplasm and the nucleus. Nuclear import of Yrb1p is mediated by two separate
      nuclear targeting signals. Export from the nucleus requires Xpo1p, but Yrb1p does
      not contain a leucine-rich NES. Instead, the interaction of Yrb1p with Xpo1p is
      mediated by Gsp1p-GTP. This novel type of export complex requires the acidic C
      terminus of Gsp1p, which is dispensable for the binding to importin beta-like
      transport receptors. A similar complex with Xpo1p and Gsp1p-GTP can be formed by
      Yrb2p, a relative of Yrb1p predominantly located in the nucleus. Yrb1p also
      functions as a disassembly factor for NES/Xpo1p/Gsp1p-GTP complexes by displacing
      the NES protein from Xpo1p/Gsp1p. This Yrb1p/Xpo1p/Gsp1p complex is then
      completely dissociated after GTP hydrolysis catalyzed by the cytoplasmic GTPase
      activating protein Rna1p.

PMID- 11251070
TI  - Positive regulation of Wee1 by Chk1 and 14-3-3 proteins.
AB  - Wee1 inactivates the Cdc2-cyclin B complex during interphase by phosphorylating
      Cdc2 on Tyr-15. The activity of Wee1 is highly regulated during the cell cycle.
      In frog egg extracts, it has been established previously that Xenopus Wee1
      (Xwee1) is present in a hypophosphorylated, active form during interphase and
      undergoes down-regulation by extensive phosphorylation at M-phase. We report that
      Xwee1 is also regulated by association with 14-3-3 proteins. Binding of 14-3-3 to
      Xwee1 occurs during interphase, but not M-phase, and requires phosphorylation of
      Xwee1 on Ser-549. A mutant of Xwee1 (S549A) that cannot bind 14-3-3 is
      substantially less active than wild-type Xwee1 in its ability to phosphorylate
      Cdc2. This mutation also affects the intranuclear distribution of Xwee1. In cell
      free kinase assays, Xchk1 phosphorylates Xwee1 on Ser-549. The results of
      experiments in which Xwee1, Xchk1, or both were immunodepleted from Xenopus egg
      extracts suggested that these two enzymes are involved in a common pathway in the
      DNA replication checkpoint response. Replacement of endogenous Xwee1 with
      recombinant Xwee1-S549A in egg extracts attenuated the cell cycle delay induced
      by addition of excess recombinant Xchk1. Taken together, these results suggest
      that Xchk1 and 14-3-3 proteins act together as positive regulators of Xwee1.

PMID- 11251071
TI  - Replication-dependent histone gene expression is related to Cajal body (CB)
      association but does not require sustained CB contact.
AB  - Interactions between Cajal bodies (CBs) and replication-dependent histone loci
      occur more frequently than for other mRNA-encoding genes, but such interactions
      are not seen with all alleles at a given time. Because CBs contain factors
      required for transcriptional regulation and 3' end processing of
      nonpolyadenylated replication-dependent histone transcripts, we investigated
      whether interaction with CBs is related to metabolism of these transcripts, known
      to vary during the cell cycle. Our experiments revealed that a locus containing a
      cell cycle-independent, replacement histone gene that produces polyadenylated
      transcripts does not preferentially associate with CBs. Furthermore, modest but
      significant changes in association levels of CBs with replication-dependent
      histone loci mimic their cell cycle modulations in transcription and 3' end
      processing rates. By simultaneously visualizing replication-dependent histone
      genes and their nuclear transcripts for the first time, we surprisingly find that
      the vast majority of loci producing detectable RNA foci do not contact CBs. These
      studies suggest some link between CB association and unusual features of
      replication-dependent histone gene expression. However, sustained CB contact is
      not a requirement for their expression, consistent with our observations of U7
      snRNP distributions. The modest correlation to gene expression instead may
      reflect transient gene signaling or the nucleation of small CBs at gene loci.

PMID- 11251072
TI  - Multifaceted physiological response allows yeast to adapt to the loss of the
      signal recognition particle-dependent protein-targeting pathway.
AB  - Translational control has recently been recognized as an important facet of
      adaptive responses to various stress conditions. We describe the adaptation
      response of the yeast Saccharomyces cerevisiae to the loss of one of two
      mechanisms to target proteins to the secretory pathway. Using inducible mutants
      that block the signal recognition particle (SRP) pathway, we find that cells
      demonstrate a physiological response to the loss of the SRP pathway that includes
      specific changes in global gene expression. Upon inducing the loss of the SRP
      pathway, SRP-dependent protein translocation is initially blocked, and cell
      growth is considerably slowed. Concomitantly, gene expression changes include the
      induction of heat shock genes and the repression of protein synthesis genes.
      Remarkably, within hours, the efficiency of protein sorting improves while cell
      growth remains slow in agreement with the persistent repression of protein
      synthesis genes. Our results suggest that heat shock gene induction serves to
      protect cells from mislocalized precursor proteins in the cytosol, whereas
      reduced protein synthesis helps to regain efficiency in protein sorting by
      reducing the load on the protein translocation apparatus. Thus, we suggest that
      cells trade speed in cell growth for fidelity in protein sorting to adjust to
      life without SRP.

PMID- 11251073
TI  - Polaris, a protein involved in left-right axis patterning, localizes to basal
      bodies and cilia.
AB  - Mutations in Tg737 cause a wide spectrum of phenotypes, including random left
      right axis specification, polycystic kidney disease, liver and pancreatic
      defects, hydrocephalus, and skeletal patterning abnormalities. To further assess
      the biological function of Tg737 and its role in the mutant pathology, we
      identified the cell population expressing Tg737 and determined the subcellular
      localization of its protein product called Polaris. Tg737 expression is
      associated with cells possessing either motile or immotile cilia and sperm.
      Similarly, Polaris concentrated just below the apical membrane in the region of
      the basal bodies and within the cilia or flagellar axoneme. The data suggest that
      Polaris functions in a ciliogenic pathway or in cilia maintenance, a role
      supported by the loss of cilia on the ependymal cell layer in ventricles of
      Tg737(orpk) brains and by the lack of node cilia in Tg737(Delta2-3betaGal)
      mutants.

PMID- 11251074
TI  - Dynamic movements of organelles containing Niemann-Pick C1 protein: NPC1
      involvement in late endocytic events.
AB  - People homozygous for mutations in the Niemann-Pick type C1 (NPC1) gene have
      physiological defects, including excess accumulation of intracellular cholesterol
      and other lipids, that lead to drastic neural and liver degeneration. The NPC1
      multipass transmembrane protein is resident in late endosomes and lysosomes, but
      its functions are unknown. We find that organelles containing functional NPC1
      fluorescent protein fusions undergo dramatic movements, some in association with
      extending strands of endoplasmic reticulum. In NPC1 mutant cells the NPC1-bearing
      organelles that normally move at high speed between perinuclear regions and the
      periphery of the cell are largely absent. Pulse-chase experiments with
      dialkylindocarbocyanine low-density lipoprotein showed that NPC1 organelles
      function late in the endocytic pathway; NPC1 protein may aid the partitioning of
      endocytic and lysosomal compartments. The close connection between NPC1 and the
      drug U18666A, which causes NPC1-like organelle defects, was established by
      rescuing drug-treated cells with overproduced NPC1. U18666A inhibits outward
      movements of NPC1 organelles, trapping membranes and cholesterol in perinuclear
      organelles similar to those in NPC1 mutant cells, even when cells are grown in
      lipoprotein-depleted serum. We conclude that NPC1 protein promotes the creation
      and/or movement of particular late endosomes, which rapidly transport materials
      to and from the cell periphery.

PMID- 11251075
TI  - GIPC and GAIP form a complex with TrkA: a putative link between G protein and
      receptor tyrosine kinase pathways.
AB  - NGF initiates the majority of its neurotrophic effects by promoting the
      activation of the tyrosine kinase receptor TrkA. Here we describe a novel
      interaction between TrkA and GIPC, a PDZ domain protein. GIPC binds to the
      juxtamembrane region of TrkA through its PDZ domain. The PDZ domain of GIPC also
      interacts with GAIP, an RGS (regulators of G protein signaling) protein. GIPC and
      GAIP are components of a G protein-coupled signaling complex thought to be
      involved in vesicular trafficking. In transfected HEK 293T cells GIPC, GAIP, and
      TrkA form a coprecipitable protein complex. Both TrkA and GAIP bind to the PDZ
      domain of GIPC, but their binding sites within the PDZ domain are different. The
      association of endogenous GIPC with the TrkA receptor was confirmed by
      coimmunoprecipitation in PC12 (615) cells stably expressing TrkA. By
      immunofluorescence GIPC colocalizes with phosphorylated TrkA receptors in
      retrograde transport vesicles located in the neurites and cell bodies of
      differentiated PC12 (615) cells. These results suggest that GIPC, like other PDZ
      domain proteins, serves to cluster transmembrane receptors with signaling
      molecules. When GIPC is overexpressed in PC12 (615) cells, NGF-induced
      phosphorylation of mitogen-activated protein (MAP) kinase (Erk1/2) decreases;
      however, there is no effect on phosphorylation of Akt, phospholipase C-gamma1, or
      Shc. The association of TrkA receptors with GIPC and GAIP plus the inhibition of
      MAP kinase by GIPC suggests that GIPC may provide a link between TrkA and G
      protein signaling pathways.

PMID- 11251076
TI  - Signaling mediated by the cytosolic domain of peptidylglycine alpha-amidating
      monooxygenase.
AB  - The luminal domains of membrane peptidylglycine alpha-amidating monooxygenase
      (PAM) are essential for peptide alpha-amidation, and the cytosolic domain (CD) is
      essential for trafficking. Overexpression of membrane PAM in corticotrope tumor
      cells reorganizes the actin cytoskeleton, shifts endogenous adrenocorticotropic
      hormone (ACTH) from mature granules localized at the tips of processes to the TGN
      region, and blocks regulated secretion. PAM-CD interactor proteins include a
      protein kinase that phosphorylates PAM (P-CIP2) and Kalirin, a Rho family GDP/GTP
      exchange factor. We engineered a PAM protein unable to interact with either P
      CIP2 or Kalirin (PAM-1/K919R), along with PAM proteins able to interact with
      Kalirin but not with P-CIP2. AtT-20 cells expressing PAM-1/K919R produce fully
      active membrane enzyme but still exhibit regulated secretion, with ACTH
      containing granules localized to process tips. Immunoelectron microscopy
      demonstrates accumulation of PAM and ACTH in tubular structures at the trans side
      of the Golgi in AtT-20 cells expressing PAM-1 but not in AtT-20 cells expressing
      PAM-1/K919R. The ability of PAM to interact with P-CIP2 is critical to its
      ability to block exit from the Golgi and affect regulated secretion. Consistent
      with this, mutation of its P-CIP2 phosphorylation site alters the ability of PAM
      to affect regulated secretion.

PMID- 11251077
TI  - An ADP-ribosylation factor GTPase-activating protein Git2-short/KIAA0148 is
      involved in subcellular localization of paxillin and actin cytoskeletal
      organization.
AB  - Paxillin acts as an adaptor protein in integrin signaling. We have shown that
      paxillin exists in a relatively large cytoplasmic pool, including perinuclear
      areas, in addition to focal complexes formed at the cell periphery and focal
      adhesions formed underneath the cell. Several ADP-ribosylation factor (ARF)
      GTPase-activating proteins (GAPs; ARFGAPs) have been shown to associate with
      paxillin. We report here that Git2-short/KIAA0148 exhibits properties of a
      paxillin-associated ARFGAP and appears to be colocalized with paxillin, primarily
      at perinuclear areas. A fraction of Git2-short was also localized to actin-rich
      structures at the cell periphery. Unlike paxillin, however, Git2-short did not
      accumulate at focal adhesions underneath the cell. Git2-short is a short isoform
      of Git2, which is highly homologous to p95PKL, another paxillin-binding protein,
      and showed a weaker binding affinity toward paxillin than that of Git2. The
      ARFGAP activities of Git2 and Git2-short have been previously demonstrated in
      vitro, and we provided evidence that at least one ARF isoform, ARF1, is an
      intracellular substrate for the GAP activity of Git2-short. We also showed that
      Git2-short could antagonize several known ARF1-mediated phenotypes:
      overexpression of Git2-short, but not its GAP-inactive mutant, caused the
      redistribution of Golgi protein beta-COP and reduced the amounts of paxillin
      containing focal adhesions and actin stress fibers. Perinuclear localization of
      paxillin, which was sensitive to ARF inactivation, was also affected by Git2
      short overexpression. On the other hand, paxillin localization to focal complexes
      at the cell periphery was unaffected or even augmented by Git2-short
      overexpression. Therefore, an ARFGAP protein weakly interacting with paxillin,
      Git2-short, exhibits pleiotropic functions involving the regulation of Golgi
      organization, actin cytoskeletal organization, and subcellular localization of
      paxillin, all of which need to be coordinately regulated during integrin-mediated
      cell adhesion and intracellular signaling.

PMID- 11251078
TI  - Molecular cloning and characterization of phocein, a protein found from the Golgi
      complex to dendritic spines.
AB  - Phocein is a widely expressed, highly conserved intracellular protein of 225
      amino acids, the sequence of which has limited homology to the sigma subunits
      from clathrin adaptor complexes and contains an additional stretch bearing a
      putative SH3-binding domain. This sequence is evolutionarily very conserved (80%
      identity between Drosophila melanogaster and human). Phocein was discovered by a
      yeast two-hybrid screen using striatin as a bait. Striatin, SG2NA, and zinedin,
      the three mammalian members of the striatin family, are multimodular, WD-repeat,
      and calmodulin-binding proteins. The interaction of phocein with striatin, SG2NA,
      and zinedin was validated in vitro by coimmunoprecipitation and pull-down
      experiments. Fractionation of brain and HeLa cells showed that phocein is
      associated with membranes, as well as present in the cytosol where it behaves as
      a protein complex. The molecular interaction between SG2NA and phocein was
      confirmed by their in vivo colocalization, as observed in HeLa cells where
      antibodies directed against either phocein or SG2NA immunostained the Golgi
      complex. A 2-min brefeldin A treatment of HeLa cells induced the redistribution
      of both proteins. Immunocytochemical studies of adult rat brain sections showed
      that phocein reactivity, present in many types of neurons, is strictly somato
      dendritic and extends down to spines, just as do striatin and SG2NA.

PMID- 11251079
TI  - Mechanisms of transforming growth factor-beta receptor endocytosis and
      intracellular sorting differ between fibroblasts and epithelial cells.
AB  - Transforming growth factor-betas (TGF-beta) are multifunctional proteins capable
      of either stimulating or inhibiting mitosis, depending on the cell type. These
      diverse cellular responses are caused by stimulating a single receptor complex
      composed of type I and type II receptors. Using a chimeric receptor model where
      the granulocyte/monocyte colony-stimulating factor receptor ligand binding
      domains are fused to the transmembrane and cytoplasmic signaling domains of the
      TGF-beta type I and II receptors, we wished to describe the role(s) of specific
      amino acid residues in regulating ligand-mediated endocytosis and signaling in
      fibroblasts and epithelial cells. Specific point mutations were introduced at
      Y182, T200, and Y249 of the type I receptor and K277 and P525 of the type II
      receptor. Mutation of either Y182 or Y249, residues within two putative consensus
      tyrosine-based internalization motifs, had no effect on endocytosis or signaling.
      This is in contrast to mutation of T200 to valine, which resulted in ablation of
      signaling in both cell types, while only abolishing receptor down-regulation in
      fibroblasts. Moreover, in the absence of ligand, both fibroblasts and epithelial
      cells constitutively internalize and recycle the TGF-beta receptor complex back
      to the plasma membrane. The data indicate fundamental differences between
      mesenchymal and epithelial cells in endocytic sorting and suggest that ligand
      binding diverts heteromeric receptors from the default recycling pool to a
      pathway mediating receptor down-regulation and signaling.

PMID- 11251080
TI  - Segregation of heterotrimeric G proteins in cell surface microdomains. G(q) binds
      caveolin to concentrate in caveolae, whereas G(i) and G(s) target lipid rafts by
      default.
AB  - Select lipid-anchored proteins such as glycosylphosphatidylinositol (GPI)
      anchored proteins and nonreceptor tyrosine kinases may preferentially partition
      into sphingomyelin-rich and cholesterol-rich plasmalemmal microdomains, thereby
      acquiring resistance to detergent extraction. Two such domains, caveolae and
      lipid rafts, are morphologically and biochemically distinct, contain many
      signaling molecules, and may function in compartmentalizing cell surface
      signaling. Subfractionation and confocal immunofluorescence microscopy reveal
      that, in lung tissue and in cultured endothelial and epithelial cells,
      heterotrimeric G proteins (G(i), G(q), G(s), and G(betagamma)) target discrete
      cell surface microdomains. G(q) specifically concentrates in caveolae, whereas
      G(i) and G(s) concentrate much more in lipid rafts marked by GPI-anchored
      proteins (5' nucleotidase and folate receptor). G(q), apparently without
      G(betagamma) subunits, stably associates with plasmalemmal and cytosolic
      caveolin. G(i) and G(s) interact with G(betagamma) subunits but not caveolin.
      G(i) and G(s), unlike G(q), readily move out of caveolae. Thus, caveolin may
      function as a scaffold to trap, concentrate, and stabilize G(q) preferentially
      within caveolae over lipid rafts. In N2a cells lacking caveolae and caveolin,
      G(q), G(i), and G(s) all concentrate in lipid rafts as a complex with
      G(betagamma). Without effective physiological interaction with caveolin, G
      proteins tend by default to segregate in lipid rafts. The ramifications of the
      segregated microdomain distribution and the G(q)-caveolin complex without
      G(betagamma) for trafficking, signaling, and mechanotransduction are discussed.

PMID- 11251082
TI  - A family of small coiled-coil-forming proteins functioning at the late endosome
      in yeast.
AB  - The multispanning membrane protein Ste6, a member of the ABC-transporter family,
      is transported to the yeast vacuole for degradation. To identify functions
      involved in the intracellular trafficking of polytopic membrane proteins, we
      looked for functions that block Ste6 transport to the vacuole upon
      overproduction. In our screen, we identified several known vacuolar protein
      sorting (VPS) genes (SNF7/VPS32, VPS4, and VPS35) and a previously
      uncharacterized open reading frame, which we named MOS10 (more of Ste6). Sequence
      analysis showed that Mos10 is a member of a small family of coiled-coil-forming
      proteins, which includes Snf7 and Vps20. Deletion mutants of all three genes
      stabilize Ste6 and show a "class E vps phenotype." Maturation of the vacuolar
      hydrolase carboxypeptidase Y was affected in the mutants and the endocytic tracer
      FM4-64 and Ste6 accumulated in a dot or ring-like structure next to the vacuole.
      Differential centrifugation experiments demonstrated that about half of the
      hydrophilic proteins Mos10 and Vps20 was membrane associated. The intracellular
      distribution was further analyzed for Mos10. On sucrose gradients, membrane
      associated Mos10 cofractionated with the endosomal t-SNARE Pep12, pointing to an
      endosomal localization of Mos10. The growth phenotypes of the mutants suggest
      that the "Snf7-family" members are involved in a cargo-specific event.

PMID- 11251081
TI  - Interaction of the E1A oncoprotein with Yak1p, a novel regulator of yeast
      pseudohyphal differentiation, and related mammalian kinases.
AB  - The C-terminal portion of adenovirus E1A suppresses ras-induced metastasis and
      tumorigenicity in mammalian cells; however, little is known about the mechanisms
      by which this occurs. In the simple eukaryote Saccharomyces cerevisiae, Ras2p,
      the homolog of mammalian h-ras, regulates mitogen-activated protein kinase (MAPK)
      and cyclic AMP-dependent protein kinase A (cAMP/PKA) signaling pathways to
      control differentiation from the yeast form to the pseudohyphal form. When
      expressed in yeast, the C-terminal region of E1A induced pseudohyphal
      differentiation, and this was independent of both the MAPK and cAMP/PKA signaling
      pathways. Using the yeast two-hybrid system, we identified an interaction between
      the C-terminal region of E1A and Yak1p, a yeast dual-specificity serine/threonine
      protein kinase that functions as a negative regulator of growth. E1A also
      physically interacts with Dyrk1A and Dyrk1B, two mammalian homologs of Yak1p, and
      stimulates their kinase activity in vitro. We further demonstrate that Yak1p is
      required in yeast to mediate pseudohyphal differentiation induced by Ras2p
      regulated signaling pathways. However, pseudohyphal differentiation induced by
      the C-terminal region of E1A is largely independent of Yak1p. These data suggest
      that mammalian Yak1p-related kinases may be targeted by the E1A oncogene to
      modulate cell growth.

PMID- 11251083
TI  - Mechanism in the sequential control of cell morphology and S phase entry by
      epidermal growth factor involves distinct MEK/ERK activations.
AB  - Cell shape plays a role in cell growth, differentiation, and death. Herein, we
      used the hepatocyte, a normal, highly differentiated cell characterized by a long
      G1 phase, to understand the mechanisms that link cell shape to growth. First,
      evidence was provided that the mitogen-activated protein kinase kinase
      (MEK)/extracellular signal-regulated kinase (ERK) cascade is a key transduction
      pathway controlling the hepatocyte morphology. MEK2/ERK2 activation in early G1
      phase did not lead to cell proliferation but induced cell shape spreading and
      demonstration was provided that this MAPK-dependent spreading was required for
      reaching G1/S transition and DNA replication. Moreover, epidermal growth factor
      (EGF) was found to control this morphogenic signal in addition to its mitogenic
      effect. Thus, blockade of cell spreading by cytochalasin D or PD98059 treatment
      resulted in inhibition of EGF-dependent DNA replication. Our data led us to
      assess the first third of G1, is exclusively devoted to the growth factor
      dependent morphogenic events, whereas the mitogenic signal occurred at only
      approximately mid-G1 phase. Moreover, these two growth factor-related sequential
      signaling events involved successively activation of MEK2-ERK2 and then MEK1/2
      ERK1/2 isoforms. In addition, we demonstrated that inhibition of extracellular
      matrix receptor, such as integrin beta1 subunit, leads to cell arrest in G1,
      whereas EGF was found to up-regulated integrin beta1 and fibronectin in a MEK-ERK
      dependent manner. This process in relation to cytoskeletal reorganization could
      induce hepatocyte spreading, making them permissive for DNA replication. Our
      results provide new insight into the mechanisms by which a growth factor can
      temporally control dual morphogenic and mitogenic signals during the G1 phase.

PMID- 11251084
TI  - The Chlamydomonas PF6 locus encodes a large alanine/proline-rich polypeptide that
      is required for assembly of a central pair projection and regulates flagellar
      motility.
AB  - Efficient motility of the eukaryotic flagellum requires precise temporal and
      spatial control of its constituent dynein motors. The central pair and its
      associated structures have been implicated as important members of a signal
      transduction cascade that ultimately regulates dynein arm activity. To identify
      central pair components involved in this process, we characterized a
      Chlamydomonas motility mutant (pf6-2) obtained by insertional mutagenesis. pf6-2
      flagella twitch ineffectively and lack the 1a projection on the C1 microtubule of
      the central pair. Transformation with constructs containing a full-length, wild
      type copy of the PF6 gene rescues the functional, structural, and biochemical
      defects associated with the pf6 mutation. Sequence analysis indicates that the
      PF6 gene encodes a large polypeptide that contains numerous alanine-rich, proline
      rich, and basic domains and has limited homology to an expressed sequence tag
      derived from a human testis cDNA library. Biochemical analysis of an epitope
      tagged PF6 construct demonstrates that the PF6 polypeptide is an axonemal
      component that cosediments at 12.6S with several other polypeptides. The PF6
      protein appears to be an essential component required for assembly of some of
      these polypeptides into the C1-1a projection.

PMID- 11251085
TI  - In vivo binding and hierarchy of assembly of the yeast RNA polymerase I
      transcription factors.
AB  - Transcription by RNA polymerase I in Saccharomyces cerevisiae requires a series
      of transcription factors that have been genetically and biochemically identified.
      In particular, the core factor (CF) and the upstream activation factor (UAF) have
      been shown in vitro to bind the core element and the upstream promoter element,
      respectively. We have analyzed in vivo the DNAse I footprinting of the 35S
      promoter in wild-type and mutant strains lacking one specific transcription
      factor at the time. In this way we were able to unambiguously attribute the
      protections by the CF and the UAF to their respective putative binding sites. In
      addition, we have found that in vivo a binding hierarchy exists, the UAF being
      necessary for CF binding. Because the CF footprinting is lost in mutants lacking
      a functional RNA polymerase I, we also conclude that the final step of
      preinitiation-complex assembly affects binding of the CF, stabilizing its contact
      with DNA. Thus, in vivo, the CF is recruited to the core element by the UAF and
      stabilized on DNA by the presence of a functional RNA polymerase I.

PMID- 11251087
TI  - A brief tour of the cell cycle.

PMID- 11251086
TI  - Centrin is necessary for the formation of the motile apparatus in spermatids of
      Marsilea.
AB  - During spermiogenesis in the water fern, Marsilea vestita, basal bodies are
      synthesized de novo in cells that lack preexisting centrioles, in a particle
      known as a blepharoplast. We have focused on basal body assembly in this
      organism, asking what components are required for blepharoplast formation.
      Spermiogenesis is a rapid process that is activated by placing dry microspores
      into water. Dry microspores contain large quantities of stored protein and stored
      mRNA, and inhibitors reveal that certain proteins are translated from stored
      transcripts at specific times during development. Centrin translation accompanies
      blepharoplast appearance, while beta-tubulin translation occurs later, during
      axonemal formation. In asking whether centrin is an essential component of the
      blepharoplast, we used antisense, sense, and double-stranded RNA probes made from
      the Marsilea centrin cDNA, MvCen1, to block centrin translation. We employed a
      novel method to introduce these RNAs directly into the cells. Antisense and sense
      both arrest spermiogenesis when blepharoplasts should appear, and dsRNA made from
      the same cDNA is an effective inhibitor at concentrations at least 10 times lower
      than either of the single-stranded RNA used in these experiments. Blepharoplasts
      are undetectable and basal bodies fail to form. Antisense, sense, and dsRNA
      probes made from Marsilea beta-tubulin permitted normal development until
      axonemes form. In controls, antisense, sense, and dsRNA, made from a segment of
      HIV, had no effect on spermiogenesis. Immunoblots suggest that translational
      blocks induced by centrin-based RNA are gene specific and concentration
      dependent, since neither beta-tubulin- nor HIV-derived RNAs affects centrin
      translation. The disruption of centrin translation affects microtubule
      distributions in spermatids, since centrin appears to control formation of the
      cytoskeleton and motile apparatus. These results show that centrin plays an
      essential role in the formation of a motile apparatus during spermiogenesis of M.
      vestita.

PMID- 11251088
TI  - Agricultural microbes genome 2: first glimpses into the genomes of plant
      associated microbes.

PMID- 11251089
TI  - Medicago truncatula on the move!

PMID- 11251090
TI  - A gain-of-function mutation in IAA28 suppresses lateral root development.
AB  - The phytohormone auxin is important in many aspects of plant development. We have
      isolated an auxin-resistant Arabidopsis mutant, iaa28-1, that is severely
      defective in lateral root formation and that has diminished adult size and
      decreased apical dominance. The iaa28-1 mutant is resistant to inhibition of root
      elongation by auxin, cytokinin, and ethylene, but it responds normally to other
      phytohormones. We identified the gene defective in the iaa28-1 mutant by using a
      map-based positional approach and found it to encode a previously uncharacterized
      member of the Aux/IAA gene family. IAA28 is preferentially expressed in roots and
      inflorescence stems, and in contrast to other Aux/IAA genes, IAA28 transcription
      is not induced by exogenous auxin. Studies of the gain-of-function iaa28-1 mutant
      suggest that IAA28 normally represses transcription, perhaps of genes that
      promote lateral root initiation in response to auxin signals.

PMID- 11251091
TI  - Sex determination in the monoecious species cucumber is confined to specific
      floral whorls.
AB  - In unisexual flowers, sex is determined by the selective repression of growth or
      the abortion of either male or female reproductive organs. The mechanism by which
      this process is controlled in plants is still poorly understood. Because it is
      known that the identity of reproductive organs in plants is controlled by
      homeotic genes belonging to the MADS box gene family, we analyzed floral homeotic
      mutants from cucumber, a species that bears both male and female flowers on the
      same individual. To study the characteristics of sex determination in more
      detail, we produced mutants similar to class A and C homeotic mutants from well
      characterized hermaphrodite species such as Arabidopsis by ectopically expressing
      and suppressing the cucumber gene CUCUMBER MADS1 (CUM1). The cucumber mutant
      green petals (gp) corresponds to the previously characterized B mutants from
      several species and appeared to be caused by a deletion of 15 amino acid residues
      in the coding region of the class B MADS box gene CUM26. These homeotic mutants
      reveal two important concepts that govern sex determination in cucumber. First,
      the arrest of either male or female organ development is dependent on their
      positions in the flower and is not associated with their sexual identity. Second,
      the data presented here strongly suggest that the class C homeotic function is
      required for the position-dependent arrest of reproductive organs.

PMID- 11251092
TI  - Dynamic analyses of the expression of the HISTONE::YFP fusion protein in
      arabidopsis show that syncytial endosperm is divided in mitotic domains.
AB  - During early seed development, nuclear divisions in the endosperm are not
      followed by cell division, leading to the development of a syncytium. The simple
      organization of the Arabidopsis endosperm provides a model in which to study the
      regulation of the cell cycle in relation to development. To monitor nuclear
      divisions, we constructed a HISTONE 2B::YELLOW FLUORESCENT PROTEIN gene fusion
      (H2B::YFP). To validate its use as a vital marker for chromatin in plants,
      H2B::YFP was expressed constitutively in Arabidopsis. This enabled the
      observation of mitoses in living root meristems. H2B::YFP was expressed
      specifically in Arabidopsis syncytial endosperm by using GAL4 transactivation.
      Monitoring mitotic activity in living syncytial endosperm showed that the
      syncytium was organized into three domains in which nuclei divide simultaneously
      with a specific time course. Each mitotic domain has a distinct spatiotemporal
      pattern of mitotic CYCLIN B1;1 accumulation. The polar spatial organization of
      the three mitotic domains suggests interactions between developmental mechanisms
      and the regulation of the cell cycle.

PMID- 11251093
TI  - Identification of a Ca(2+)-pectate binding site on an apoplastic peroxidase.
AB  - An apoplastic isoperoxidase from zucchini (APRX) was shown to bind strongly to
      polygalacturonic acid in their Ca(2)+-induced conformation. By homology modeling,
      we were able to identify a motif of four clustered arginines (positions 117, 262,
      268, and 271) that could be responsible for this binding. To verify the role of
      these arginine residues in the binding process, we prepared three mutants of APRX
      (M1, R117S; M2, R262Q/R268S; and M3, R262Q/R268S/R271Q). APRX and the three
      mutants were expressed as recombinant glycoproteins by the baculovirus-insect
      cell system. This procedure yielded four active enzymes with similar molecular
      masses that were tested for their ability to bind Ca(2)+-pectate. Recombinant
      wild-type APRX exhibited an affinity for the pectic structure comparable to that
      of the native plant isoperoxidase. The mutations impaired binding depending on
      the number of arginine residues that were replaced. M1 and M2 showed intermediate
      affinities, whereas M3 did not bind at all. This was demonstrated using an in
      vitro binding test and on cell walls of hypocotyl cross-sections. It can be
      concluded that APRX bears a Ca(2)+-pectate binding site formed by four clustered
      arginines. This site could ensure that APRX is properly positioned in cell walls,
      using unesterified domains of pectins as a scaffold.

PMID- 11251094
TI  - Isolation and characterization of rice phytochrome A mutants.
AB  - To elucidate phytochrome A (phyA) function in rice, we screened a large
      population of retrotransposon (Tos17) insertional mutants by polymerase chain
      reaction and isolated three independent phyA mutant lines. Sequencing of the
      Tos17 insertion sites confirmed that the Tos17s interrupted exons of PHYA genes
      in these mutant lines. Moreover, the phyA polypeptides were not immunochemically
      detectable in these phyA mutants. The seedlings of phyA mutants grown in
      continuous far-red light showed essentially the same phenotype as dark-grown
      seedlings, indicating the insensitivity of phyA mutants to far-red light. The
      etiolated seedlings of phyA mutants also were insensitive to a pulse of far-red
      light or very low fluence red light. In contrast, phyA mutants were
      morphologically indistinguishable from wild type under continuous red light.
      Therefore, rice phyA controls photomorphogenesis in two distinct modes of
      photoperception--far-red light-dependent high irradiance response and very low
      fluence response--and such function seems to be unique and restricted to the
      deetiolation process. Interestingly, continuous far-red light induced the
      expression of CAB and RBCS genes in rice phyA seedlings, suggesting the existence
      of a photoreceptor(s) other than phyA that can perceive continuous far-red light
      in the etiolated seedlings.

PMID- 11251095
TI  - A small decrease of plastid transketolase activity in antisense tobacco
      transformants has dramatic effects on photosynthesis and phenylpropanoid
      metabolism.
AB  - Transketolase (TK) catalyzes reactions in the Calvin cycle and the oxidative
      pentose phosphate pathway (OPPP) and produces erythrose-4-phosphate, which is a
      precursor for the shikimate pathway leading to phenylpropanoid metabolism. To
      investigate the consequences of decreased TK expression for primary and secondary
      metabolism, we transformed tobacco with a construct containing an antisense TK
      sequence. The results were as follows: (1) a 20 to 40% reduction of TK activity
      inhibited ribulose-1,5-bisphosphate regeneration and photosynthesis. The
      inhibition of photosynthesis became greater as irradiance increased across the
      range experienced in growth conditions (170 to 700 micromol m(-2) sec(-1)). TK
      almost completely limited the maximum rate of photosynthesis in saturating light
      and saturating CO(2). (2) Decreased expression of TK led to a preferential
      decrease of sugars, whereas starch remained high until photosynthesis was
      strongly inhibited. One of the substrates of TK (fructose-6-phosphate) is the
      starting point for starch synthesis, and one of the products (erythrose-4
      phosphate) inhibits phosphoglucose isomerase, which catalyzes the first reaction
      leading to starch. (3) A 20 to 50% decrease of TK activity led to decreased
      levels of aromatic amino acids and decreased levels of the intermediates (caffeic
      acid and hydroxycinnamic acids) and products (chlorogenic acid, tocopherol, and
      lignin) of phenylpropanoid metabolism. (4) There was local loss of chlorophyll
      and carotene on the midrib when TK activity was inhibited by >50%, spreading onto
      minor veins and lamina in severely affected transformants. (5) OPPP activity was
      not strongly inhibited by decreased TK activity. These results identify TK
      activity as an important determinant of photosynthetic and phenylpropanoid
      metabolism and show that the provision of precursors by primary metabolism
      colimits flux into the shikimate pathway and phenylpropanoid metabolism.

PMID- 11251096
TI  - Expression and post-transcriptional regulation of maize transposable element MuDR
      and its derivatives.
AB  - The transposition of Mu elements underlying Mutator activity in maize requires a
      transcriptionally active MuDR element. Despite variation in MuDR copy number and
      RNA levels in Mutator lines, transposition events are consistently late in plant
      development, and Mu excision frequencies are similar. Here, we report previously
      unsuspected and ubiquitous MuDR homologs that produce both RNA and protein. MuDR
      transcript levels are proportional to MuDR copy number, and homolog transcript
      levels increase in active Mutator lines. A subset of homologs exhibits
      constitutive transcription in MuDR(-) and epigenetically silenced MuDR lines,
      suggesting independent transcriptional regulation. Surprisingly, immunodetection
      demonstrated nearly invariant levels of MuDR and homolog protein products in all
      tested Mutator and non-Mutator stocks. These results suggest a strict control
      over protein production, which might explain the uniform excision frequency of Mu
      elements. Moreover, the nonfunctional proteins encoded by homologs may negatively
      regulate Mutator activity and represent part of the host defense against this
      transposon family.

PMID- 11251097
TI  - HC-Pro suppression of transgene silencing eliminates the small RNAs but not
      transgene methylation or the mobile signal.
AB  - Post-transcriptional gene silencing (PTGS) is a sequence-specific RNA degradation
      mechanism that is widespread in eukaryotic organisms. It is often associated with
      methylation of the transcribed region of the silenced gene and with accumulation
      of small RNAs (21 to 25 nucleotides) homologous to the silenced gene. In plants,
      PTGS can be triggered locally and then spread throughout the organism via a
      mobile signal that can cross a graft junction. Previously, we showed that the
      helper component-proteinase (HC-Pro) of plant potyviruses suppresses PTGS. Here,
      we report that plants in which PTGS has been suppressed by HC-Pro fail to
      accumulate the small RNAs associated with silencing. However, the transgene locus
      of these plants remains methylated. Grafting experiments indicate that HC-Pro
      prevents the plant from responding to the mobile silencing signal but does not
      eliminate its ability to produce or send the signal. These results demonstrate
      that HC-Pro functions downstream of transgene methylation and the mobile signal
      at a step preceding accumulation of the small RNAs.

PMID- 11251099
TI  - Targeted histone acetylation and altered nuclease accessibility over short
      regions of the pea plastocyanin gene.
AB  - The chromatin structure of the pea plastocyanin gene (PetE) was examined at three
      different transcriptional states by investigating the acetylation states of
      histones H3 and H4 and the nuclease accessibility of the gene in pea roots,
      etiolated shoots, and green shoots. The acetylation states of histones associated
      with different regions of PetE were analyzed by chromatin immunoprecipitation
      with antibodies specific for acetylated or nonacetylated histone H3 or H4 tails,
      followed by polymerase chain reaction quantification. Comparison of pea tissues
      indicated that histone hyperacetylation was associated with increased PetE
      transcription in green shoots. Moreover, hyperacetylation of both histones H3 and
      H4 was targeted to the enhancer/promoter region in green shoots, suggesting that
      only specific nucleosomes along the gene were modified. Time-course digestions of
      nuclei with micrococcal nuclease and DNaseI indicated that the enhancer/promoter
      region was more resistant to digestion in the inactive gene in pea roots than was
      the same region in the active gene in shoots, whereas the transcribed region of
      PetE was digested similarly among the tissues. This finding indicates that
      transcription is accompanied by changes in the nuclease accessibility of the
      enhancer/promoter region only. Moreover, these results indicate that the changes
      in nuclease accessibility are organ specific, whereas histone hyperacetylation is
      light dependent, and they suggest that changes in nuclease accessibility precede
      histone hyperacetylation during PetE activation.

PMID- 11251098
TI  - Cell cycle in the fucus zygote parallels a somatic cell cycle but displays a
      unique translational regulation of cyclin-dependent kinases.
AB  - In eukaryotic cells, the basic machinery of cell cycle control is highly
      conserved. In particular, many cellular events during cell cycle progression are
      controlled by cyclin-dependent kinases (CDKs). The cell cycle in animal early
      embryos, however, differs substantially from that of somatic cells or yeasts. For
      example, cell cycle checkpoints that ensure that the sequence of cell cycle
      events is correct have been described in somatic cells and yeasts but are largely
      absent in embryonic cells. Furthermore, the regulation of CDKs is substantially
      different in the embryonic and somatic cells. In this study, we address the
      nature of the first cell cycle in the brown alga Fucus, which is evolutionarily
      distant from the model systems classically used for cell cycle studies in
      embryos. This cycle consists of well-defined G1, S, G2, and M phases. The purine
      derivative olomoucine inhibited CDKs activity in vivo and in vitro and induced
      different cell cycle arrests, including at the G1/S transition, suggesting that,
      as in somatic cells, CDKs tightly control cell cycle progression. The cell cycle
      of Fucus zygotes presented the other main features of a somatic cell cycle, such
      as a functional spindle assembly checkpoint that targets CDKs and the regulation
      of the early synthesis of two PSTAIRE CDKs, p32 and p34, and the associated
      histone H1 kinase activity as well as the regulation of CDKs by tyrosine
      phosphorylation. Surprisingly, the synthesis after fertilization of p32 and p34
      was translationally regulated, a regulation not described previously for CDKs.
      Finally, our results suggest that the activation of mitotic CDKs relies on an
      autocatalytic amplification mechanism.

PMID- 11251100
TI  - Lipoxygenase is involved in the control of potato tuber development.
AB  - Plant lipoxygenases (LOXs) are a functionally diverse class of dioxygenases
      implicated in physiological processes such as growth, senescence, and stress
      related responses. LOXs incorporate oxygen into their fatty acid substrates and
      produce hydroperoxide fatty acids that are precursors of jasmonic acid and
      related compounds. Here, we report the involvement of the tuber-associated LOXs,
      designated the Lox1 class, in the control of tuber growth. RNA hybridization
      analysis showed that the accumulation of Lox1 class transcripts was restricted to
      developing tubers, stolons, and roots and that mRNA accumulation correlated
      positively with tuber initiation and growth. In situ hybridization showed that
      Lox1 class transcripts accumulated in the apical and subapical regions of the
      newly formed tuber, specifically in the vascular tissue of the perimedullary
      region, the site of the most active cell growth during tuber enlargement.
      Suppression mutants produced by expressing antisense coding sequence of a
      specific tuber LOX, designated POTLX-1, exhibited a significant reduction in LOX
      activity in stolons and tubers. The suppression of LOX activity correlated with
      reduced tuber yield, decreased average tuber size, and a disruption of tuber
      formation. Our results indicate that the pathway initiated by the expression of
      the Lox1 class genes of potato is involved in the regulation of tuber
      enlargement.

PMID- 11251101
TI  - Self-incompatibility in the genus Arabidopsis: characterization of the S locus in
      the outcrossing A. lyrata and its autogamous relative A. thaliana.
AB  - As a starting point for a phylogenetic study of self-incompatibility (SI) in
      crucifers and to elucidate the genetic basis of transitions between outcrossing
      and self-fertilizing mating systems in this family, we investigated the SI system
      of Arabidopsis lyrata. A. lyrata is an outcrossing close relative of the self
      fertile A. thaliana and is thought to have diverged from A. thaliana
      approximately 5 million years ago and from Brassica spp 15 to 20 million years
      ago. Analysis of two S (sterility) locus haplotypes demonstrates that the A.
      lyrata S locus contains tightly linked orthologs of the S locus receptor kinase
      (SRK) gene and the S locus cysteine-rich protein (SCR) gene, which are the
      determinants of SI specificity in stigma and pollen, respectively, but lacks an S
      locus glycoprotein gene. As described previously in Brassica, the S haplotypes of
      A. lyrata differ by the rearranged order of their genes and by their variable
      physical sizes. Comparative mapping of the A. lyrata and Brassica S loci
      indicates that the S locus of crucifers is a dynamic locus that has undergone
      several duplication events since the Arabidopsis--Brassica split and was
      translocated as a unit between two distant chromosomal locations during
      diversification of the two taxa. Furthermore, comparative analysis of the S locus
      region of A. lyrata and its homeolog in self-fertile A. thaliana identified
      orthologs of the SRK and SCR genes and demonstrated that self-compatibility in
      this species is associated with inactivation of SI specificity genes.

PMID- 11251103
TI  - Disruption of individual members of Arabidopsis syntaxin gene families indicates
      each has essential functions.
AB  - Syntaxins are a large group of proteins found in all eukaryotes involved in the
      fusion of transport vesicles to target membranes. Twenty-four syntaxins grouped
      into 10 gene families are found in the model plant Arabidopsis thaliana, each
      group containing one to five paralogous members. The Arabidopsis SYP2 and SYP4
      gene families contain three members each that share 60 to 80% protein sequence
      identity. Gene disruptions of the yeast (Saccharomyces cerevisiae) orthologs of
      the SYP2 and SYP4 gene families (Pep12p and Tlg2p, respectively) indicate that
      these syntaxins are not essential for growth in yeast. However, we have isolated
      and characterized gene disruptions in two genes from each family, finding that
      disruption of individual syntaxins from these families is lethal in the male
      gametophyte of Arabidopsis. Complementation of the syp21-1 gene disruption with
      its cognate transgene indicated that the lethality is linked to the loss of the
      single syntaxin gene. Thus, it is clear that each syntaxin in the SYP2 and SYP4
      families serves an essential nonredundant function.

PMID- 11251102
TI  - Many parallel losses of infA from chloroplast DNA during angiosperm evolution
      with multiple independent transfers to the nucleus.
AB  - We used DNA sequencing and gel blot surveys to assess the integrity of the
      chloroplast gene infA, which codes for translation initiation factor 1, in >300
      diverse angiosperms. Whereas most angiosperms appear to contain an intact
      chloroplast infA gene, the gene has repeatedly become defunct in approximately 24
      separate lineages of angiosperms, including almost all rosid species. In four
      species in which chloroplast infA is defunct, transferred and expressed copies of
      the gene were found in the nucleus, complete with putative chloroplast transit
      peptide sequences. The transit peptide sequences of the nuclear infA genes from
      soybean and Arabidopsis were shown to be functional by their ability to target
      green fluorescent protein to chloroplasts in vivo. Phylogenetic analysis of infA
      sequences and assessment of transit peptide homology indicate that the four
      nuclear infA genes are probably derived from four independent gene transfers from
      chloroplast to nuclear DNA during angiosperm evolution. Considering this and the
      many separate losses of infA from chloroplast DNA, the gene has probably been
      transferred many more times, making infA by far the most mobile chloroplast gene
      known in plants.

PMID- 11251104
TI  - Gibberellin/abscisic acid antagonism in barley aleurone cells: site of action of
      the protein kinase PKABA1 in relation to gibberellin signaling molecules.
AB  - The antagonism between gibberellins (GA) and abscisic acid (ABA) is an important
      factor regulating the developmental transition from embryogenesis to seed
      germination. In barley aleurone layers, the expression of genes encoding alpha
      amylases and proteases is induced by GA but suppressed by ABA. It has been shown
      that an ABA-induced protein kinase, PKABA1, mediates the ABA suppression of alpha
      amylase expression. Using a barley aleurone transient expression system, we have
      now localized the site of action of PKABA1 relative to other signal transduction
      components governing the expression of alpha-amylase. The expression of alpha
      amylase can be transactivated by the transcription factor GAMyb, which is itself
      induced by GA. A truncated GAMyb containing the DNA binding domain but lacking
      the transactivation domain prevents the GA induction of alpha-amylase, further
      supporting the notion that GAMyb mediates the GA induction of alpha-amylase
      expression. Although ABA and PKABA1 strongly inhibit the GA induction of alpha
      amylase, they have no effect on GAMyb-transactivated alpha-amylase expression.
      Using a GAMyb promoter--beta-glucuronidase construct, we also show that both ABA
      and PKABA1 repress the GA induction of GAMyb. In the slender mutant, GAMyb and
      alpha-amylase are highly expressed, even in the absence of GA. However, this
      constitutive expression can still be inhibited by ABA, PKABA1, or an inhibitor of
      cGMP synthesis. On the basis of these observations, we suggest that PKABA1 acts
      upstream from the formation of functional GAMyb but downstream from the site of
      action of the Slender gene product. Because PKABA1 inhibits the GA induction of
      the GAMyb promoter--beta-glucuronidase construct, it appears that at least part
      of the action of PKABA1 is to downregulate GAMyb at the transcriptional level.

PMID- 11251105
TI  - Gene duplication in the diversification of secondary metabolism: tandem 2
      oxoglutarate-dependent dioxygenases control glucosinolate biosynthesis in
      Arabidopsis.
AB  - Secondary metabolites are a diverse set of plant compounds believed to have
      numerous functions in plant-environment interactions. The large chemical
      diversity of secondary metabolites undoubtedly arises from an equally diverse set
      of enzymes responsible for their biosynthesis. However, little is known about the
      evolution of enzymes involved in secondary metabolism. We are studying the
      biosynthesis of glucosinolates, a large group of secondary metabolites, in
      Arabidopsis to investigate the evolution of enzymes involved in secondary
      metabolism. Arabidopsis contains natural variations in the presence of
      methylsulfinylalkyl, alkenyl, and hydroxyalkyl glucosinolates. In this article,
      we report the identification of genes encoding two 2-oxoglutarate--dependent
      dioxygenases that are responsible for this variation. These genes, AOP2 and AOP3,
      which map to the same position on chromosome IV, result from an apparent gene
      duplication and control the conversion of methylsulfinylalkyl glucosinolate to
      either the alkenyl or the hydroxyalkyl form. By heterologous expression in
      Escherichia and the correlation of gene expression patterns to the glucosinolate
      phenotype, we show that AOP2 catalyzes the conversion of methylsulfinylalkyl
      glucosinolates to alkenyl glucosinolates. Conversely, AOP3 directs the formation
      of hydroxyalkyl glucosinolates from methylsulfinylalkyl glucosinolates. No
      ecotype coexpressed both genes. Furthermore, the absence of functional AOP2 and
      AOP3 leads to the accumulation of the precursor methylsulfinylalkyl
      glucosinolates. A third member of this gene family, AOP1, is present in at least
      two forms and found in all ecotypes examined. However, its catalytic role is
      still uncertain.

PMID- 11251106
TI  - Identification of a mannitol transporter, AgMaT1, in celery phloem.
AB  - A celery petiole phloem cDNA library was constructed and used to identify a cDNA
      that gives Saccharomyces cerevisiae cells the ability to grow on mannitol and
      transport radiolabeled mannitol in a manner consistent with a proton symport
      mechanism. This cDNA was named AgMaT1 (Apium graveolens mannitol transporter 1).
      The expression profile in source leaves and phloem was in agreement with a role
      for mannitol in phloem loading in celery. The identification in eukaryotes of a
      mannitol transporter is important because mannitol is not only a primary
      photosynthetic product in species such as celery but is also considered a
      compatible solute and antioxidant implicated in resistance to biotic and abiotic
      stress.

PMID- 11251108
TI  - O2- ions and the Mars labeled release response.

PMID- 11251107
TI  - Novel filaments 5 nm in diameter constitute the cytosolic ring of the plastid
      division apparatus.
AB  - The plastid division apparatus (called the plastid-dividing ring) has been
      detected in several plant and algal species at the constricted region of plastids
      by transmission electron microscopy. The apparatus is composed of two or three
      rings: an outer ring in the cytosol, an inner ring in the stroma, and a middle
      ring in the intermembrane space. The components of these rings are not clear.
      FtsZ, which forms the bacterial cytokinetic ring, has been proposed as a
      component of both the inner and outer rings. Here, we present the ultrastructure
      of the outer ring at high resolution. To visualize the outer ring by negative
      staining, we isolated dividing chloroplasts from a synchronized culture of a red
      alga, Cyanidioschyzon merolae, and lysed them with nonionic detergent Nonidet P
      40. Nonidet P-40 extracted primarily stroma, thylakoids, and the inner and middle
      rings, leaving the envelope and outer ring largely intact. Negative staining
      revealed that the outer ring consists of a bundle of 5-nm filaments in which
      globular proteins are spaced 4.8 nm apart. Immunoblotting using an FtsZ-specific
      antibody failed to show immunoreactivity in the fraction containing the filament.
      Moreover, the filament structure and properties are unlike those of known
      cytoskeletal filaments. The bundle of filaments forms a very rigid structure and
      does not disassemble in 2 M urea. We also identified a dividing phase-specific 56
      kD protein of chloroplasts as a candidate component of the ring. Our results
      suggest that the main architecture of the outer ring did not descend from
      cyanobacteria during the course of endosymbiosis but was added by the host cell
      early in plant evolution.

PMID- 11251110
TI  - Dynamics of water molecules in aqueous solvation shells.
AB  - We report on the direct measurement of the dynamics of water molecules in the
      solvation shell of an ion in aqueous solution. The hydrogen-bond dynamics of
      water molecules solvating a Cl-, Br-, or I- anion is slow compared with neat
      liquid water, indicating that the aqueous solvation shells of these ions are
      rigid. This rigidity can play an important role in the overall dynamics of
      chemical reactions in aqueous solution. The experiments were performed with
      femtosecond midinfrared nonlinear spectroscopy, because this technique allows the
      spectral response of the water molecules in the solvation shell to be
      distinguished clearly from that of the other water molecules in the solution.

PMID- 11251109
TI  - Colloidal nanocrystal shape and size control: the case of cobalt.
AB  - We show that a relatively simple approach for controlling the colloidal synthesis
      of anisotropic cadmium selenide semiconductor nanorods can be extended to the
      size-controlled preparation of magnetic cobalt nanorods as well as spherically
      shaped nanocrystals. This approach helps define a minimum feature set needed to
      separately control the sizes and shapes of nanocrystals. The resulting cobalt
      nanocrystals produce interesting two- and three-dimensional superstructures,
      including ribbons of nanorods.

PMID- 11251111
TI  - Autoionization in liquid water.
AB  - The dissociation of a water molecule in liquid water is the fundamental event in
      acid-base chemistry, determining the pH of water. Because of the short time
      scales and microscopic length scales involved, the dynamics of this
      autoionization have not been directly probed by experiment. Here, the
      autoionization mechanism is revealed by sampling and analyzing ab initio
      molecular dynamics trajectories. We identify the rare fluctuations in solvation
      energies that destabilize an oxygen-hydrogen bond. Through the transfer of
      protons along a hydrogen bond "wire," the nascent ions separate by three or more
      neighbors. If the hydrogen bond wire connecting the two ions is subsequently
      broken, a metastable charge-separated state is visited. The ions may then diffuse
      to large separations. If, however, the hydrogen bond wire remains unbroken, the
      ions recombine rapidly. Because of their concomitant large electric fields, the
      transient ionic species produced in this case may provide an experimentally
      detectable signal of the dynamics we report.

PMID- 11251112
TI  - Photoinduction of fast, reversible translational motion in a hydrogen-bonded
      molecular shuttle.
AB  - A rotaxane is described in which a macrocycle moves reversibly between two
      hydrogen-bonding stations after a nanosecond laser pulse. Observation of
      transient changes in the optical absorption spectrum after photoexcitation allows
      direct quantitative monitoring of the submolecular translational process. The
      rate of shuttling was determined and the influence of the surrounding medium was
      studied: At room temperature in acetonitrile, the photoinduced movement of the
      macrocycle to the second station takes about 1 microsecond and, after charge
      recombination (about 100 microseconds), the macrocycle shuttles back to its
      original position. The process is reversible and cyclable and has properties
      characteristic of an energy-driven piston.

PMID- 11251113
TI  - Tropical tropospheric ozone and biomass burning.
AB  - New methods for retrieving tropospheric ozone column depth and absorbing aerosol
      (smoke and dust) from the Earth Probe-Total Ozone Mapping Spectrometer (EP/TOMS)
      are used to follow pollution and to determine interannual variability and trends.
      During intense fires over Indonesia (August to November 1997), ozone plumes,
      decoupled from the smoke below, extended as far as India. This ozone overlay a
      regional ozone increase triggered by atmospheric responses to the El Nino and
      Indian Ocean Dipole. Tropospheric ozone and smoke aerosol measurements from the
      Nimbus 7 TOMS instrument show El Nino signals but no tropospheric ozone trend in
      the 1980s. Offsets between smoke and ozone seasonal maxima point to multiple
      factors determining tropical tropospheric ozone variability.

PMID- 11251114
TI  - Synchronous tropical South China Sea SST change and Greenland warming during
      deglaciation.
AB  - The tropical ocean plays a major role in global climate. It is therefore crucial
      to establish the precise phase between tropical and high-latitude climate
      variability during past abrupt climate events in order to gain insight into the
      mechanisms of global climate change. Here we present alkenone sea surface
      temperature (SST) records from the tropical South China Sea that show an abrupt
      temperature increase of at least 1 degrees C at the end of the last glacial
      period. Within the recognized dating uncertainties, this SST increase is
      synchronous with the Bolling warming observed at 14.6 thousand years ago in the
      Greenland Ice Sheet Project 2 ice core.

PMID- 11251115
TI  - Role of the ABC transporter Mdl1 in peptide export from mitochondria.
AB  - ATP-binding cassette (ABC) adenosine triphosphatases actively transport a wide
      variety of compounds across biological membranes. Here, the ABC protein Mdl1 was
      identified as an intracellular peptide transporter localized in the inner
      membrane of yeast mitochondria. Mdl1 was required for mitochondrial export of
      peptides with molecular masses of approximately 2100 to 600 daltons generated by
      proteolysis of inner-membrane proteins by the m-AAA protease in the mitochondrial
      matrix. Proteolysis by the i-AAA protease in the intermembrane space led to the
      release of similar-sized peptides independent of Mdl1. Thus, two pathways of
      peptide efflux from mitochondria exist that may allow communication between
      mitochondria and their cellular environment.

PMID- 11251116
TI  - Arabidopsis NPL1: a phototropin homolog controlling the chloroplast high-light
      avoidance response.
AB  - Chloroplasts relocate their positions in a cell in response to the intensity of
      incident light, moving to the side wall of the cell to avoid strong light, but
      gathering at the front face under weak light to maximize light interception.
      Here, Arabidopsis thaliana mutants defective in the avoidance response were
      isolated, and the mutated gene was identified as NPL1 (NPH-like 1), a homolog of
      NPH1 (nonphototropic hypocotyl 1), a blue light receptor used in phototropism.
      Hence, NPL1 is likely a blue light receptor regulating the avoidance response
      under strong light.

PMID- 11251117
TI  - Defensive function of herbivore-induced plant volatile emissions in nature.
AB  - Herbivore attack is known to increase the emission of volatiles, which attract
      predators to herbivore-damaged plants in the laboratory and agricultural systems.
      We quantified volatile emissions from Nicotiana attenuata plants growing in
      natural populations during attack by three species of leaf-feeding herbivores and
      mimicked the release of five commonly emitted volatiles individually. Three
      compounds (cis-3-hexen-1-ol, linalool, and cis-alpha-bergamotene) increased egg
      predation rates by a generalist predator; linalool and the complete blend
      decreased lepidopteran oviposition rates. As a consequence, a plant could reduce
      the number of herbivores by more than 90% by releasing volatiles. These results
      confirm that indirect defenses can operate in nature.

PMID- 11251118
TI  - A sperm cytoskeletal protein that signals oocyte meiotic maturation and
      ovulation.
AB  - Caenorhabditis elegans oocytes, like those of most animals, arrest during meiotic
      prophase. Sperm promote the resumption of meiosis (maturation) and contraction of
      smooth muscle-like gonadal sheath cells, which are required for ovulation. We
      show that the major sperm cytoskeletal protein (MSP) is a bipartite signal for
      oocyte maturation and sheath contraction. MSP also functions in sperm locomotion,
      playing a role analogous to actin. Thus, during evolution, MSP has acquired
      extracellular signaling and intracellular cytoskeletal functions for
      reproduction. Proteins with MSP-like domains are found in plants, fungi, and
      other animals, suggesting that related signaling functions may exist in other
      phyla.

PMID- 11251119
TI  - Sonic hedgehog control of size and shape in midbrain pattern formation.
AB  - Little is known about how patterns of cell types are organized to form brain
      structures of appropriate size and shape. To study this process, we employed in
      vivo electroporation during midbrain development to create ectopic sources of
      Sonic Hedgehog, a signaling molecule previously shown to specify different
      neuronal cell types in a concentration-dependent manner in vitro. We provide
      direct evidence that a Sonic Hedgehog source can control pattern at a distance in
      brain development and demonstrate that the size, shape, and orientation of the
      cell populations produced depend on the geometry of the morphogen source. Thus, a
      single regulatory molecule can coordinate tissue size and shape with cell-type
      identity in brain development.

PMID- 11251120
TI  - Structure of an extracellular gp130 cytokine receptor signaling complex.
AB  - The activation of gp130, a shared signal-transducing receptor for a family of
      cytokines, is initiated by recognition of ligand followed by oligomerization into
      a higher order signaling complex. Kaposi's sarcoma-associated herpesvirus encodes
      a functional homolog of human interleukin-6 (IL-6) that activates human gp130. In
      the 2.4 angstrom crystal structure of the extracellular signaling assembly
      between viral IL-6 and human gp130, two complexes are cross-linked into a
      tetramer through direct interactions between the immunoglobulin domain of gp130
      and site III of viral IL-6, which is necessary for receptor activation. Unlike
      human IL-6 (which uses many hydrophilic residues), the viral cytokine largely
      uses hydrophobic amino acids to contact gp130, which enhances the complementarity
      of the viral IL-6-gp130 binding interfaces. The cross-reactivity of gp130 is
      apparently due to a chemical plasticity evident in the amphipathic gp130 cytokine
      binding sites.

PMID- 11251121
TI  - 5'-Deoxyribose phosphate lyase activity of human DNA polymerase iota in vitro.
AB  - DNA polymerase iota (pol iota) is one of several recently discovered DNA
      polymerases in mammalian cells whose function is unknown. We report here that
      human pol iota has an intrinsic 5'-deoxyribose phosphate (dRP) lyase activity. In
      reactions reconstituted with uracil-DNA glycosylase (UDG), apurinic/apyrimidinic
      (AP) endonuclease and DNA ligase I, pol iota can use its dRP lyase and polymerase
      activities to repair G*U and A*U pairs in DNA. These data and three distinct
      catalytic properties of pol iota implicate it in specialized forms of base
      excision repair (BER).

PMID- 11251122
TI  - An RNA ligase essential for RNA editing and survival of the bloodstream form of
      Trypanosoma brucei.
AB  - RNA editing in trypanosomes occurs by a series of enzymatic steps that are
      catalyzed by a macromolecular complex. The TbMP52 protein is shown to be a
      component of this complex, to have RNA ligase activity, and to be one of two
      adenylatable proteins in the complex. Regulated repression of TbMP52 blocks
      editing, which shows that it is a functional component of the editing complex.
      This repression is lethal in bloodforms of the parasite, indicating that editing
      is essential in the mammalian stage of the life cycle. The editing complex, which
      is present in all kinetoplastid parasites, may thus be a chemotherapeutic target.

PMID- 11251123
TI  - Defective lymphotoxin-beta receptor-induced NF-kappaB transcriptional activity in
      NIK-deficient mice.
AB  - The role of NF-kappaB-inducing kinase (NIK) in cytokine signaling remains
      controversial. To identify the physiologic functions of NIK, we disrupted the NIK
      locus by gene targeting. Although NIK-/- mice displayed abnormalities in both
      lymphoid tissue development and antibody responses, NIK-/- cells manifested
      normal NF-kappaB DNA binding activity when treated with a variety of cytokines,
      including tumor necrosis factor (TNF), interleukin-1 (IL-1), and lymphotoxin-beta
      (LTbeta). However, NIK was selectively required for gene transcription induced
      through ligation of LTbeta receptor but not TNF receptors. These results reveal
      that NIK regulates the transcriptional activity of NF-kappaB in a receptor
      restricted manner.

PMID- 11251124
TI  - Dyslexia: cultural diversity and biological unity.
AB  - The recognition of dyslexia as a neurodevelopmental disorder has been hampered by
      the belief that it is not a specific diagnostic entity because it has variable
      and culture-specific manifestations. In line with this belief, we found that
      Italian dyslexics, using a shallow orthography which facilitates reading,
      performed better on reading tasks than did English and French dyslexics. However,
      all dyslexics were equally impaired relative to their controls on reading and
      phonological tasks. Positron emission tomography scans during explicit and
      implicit reading showed the same reduced activity in a region of the left
      hemisphere in dyslexics from all three countries, with the maximum peak in the
      middle temporal gyrus and additional peaks in the inferior and superior temporal
      gyri and middle occipital gyrus. We conclude that there is a universal
      neurocognitive basis for dyslexia and that differences in reading performance
      among dyslexics of different countries are due to different orthographies.

PMID- 11251125
TI  - Coronary artery surgery for ischemic heart failure: risks, benefits, and the
      importance of assessment of myocardial viability.
AB  - Heart failure and left ventricular dysfunction are common and are most often
      caused by myocardial ischemia/infarction secondary to occlusive coronary artery
      disease. Although recent refinements in medical therapy have resulted in improved
      survival, morbidity and mortality remain high in patients with advanced heart
      failure. Heart transplantation remains an option for selected patients, and
      implantable left ventricular assist devices may soon provide another treatment
      strategy for such patients. However, patients with established postischemic heart
      failure, significant myocardial viability, and coronary artery anatomy amenable
      to surgical revascularization can derive significant functional and survival
      benefit after coronary artery surgery, albeit with an increased perioperative
      risk. We discuss the role of coronary artery surgery in ischemic heart failure
      and review the evidence for such an approach.

PMID- 11251126
TI  - The pathophysiology of myocardial hibernation: current controversies and future
      directions.
AB  - It is now widely accepted that patients with chronic coronary artery disease can
      experience prolonged regional ischemic dysfunction that does not necessarily
      arise from irreversible tissue damage and, to some extent, can be reversed by
      restoration of blood flow. Recent clinical and experimental data suggest that
      this form of chronic but reversible left ventricular dysfunction represents a
      complex, progressive, and dynamic phenomenon. The initial stages of dysfunction
      are probably caused by chronic stunning. They are characterized by normal resting
      perfusion but reduced flow reserve, mild myocyte alterations, maintained membrane
      integrity (allowing the transport of both thallium and glucose), preserved
      capacity to respond to an inotropic stimulus, and no or little tissue fibrosis.
      After revascularization, functional recovery will probably be rapid and complete.
      On the other hand, the more advanced stages of dysfunction likely correspond to
      chronic hibernation. They usually are associated with reduced rest perfusion;
      increased tissue fibrosis; more severe myocyte alterations (degeneration[?],
      apoptosis); and a decreased ability to respond to inotropic stimuli. Nonetheless,
      membrane function and glucose metabolism may long remain preserved. After
      revascularization, functional recovery, if any, will probably be quite delayed
      and mostly incomplete.

PMID- 11251127
TI  - The contribution of positron emission tomography to the study of ischemic heart
      failure.
AB  - Cardiac imaging with positron emission tomography offers unrivaled sensitivity
      and specificity to probe cardiovascular physiology in health and disease. The use
      of positron emission tomography to noninvasively measure regional myocardial
      blood flow and assess myocardial viability in patients with ventricular
      dysfunction and coronary artery disease has contributed greatly to our
      understanding of the pathophysiology of ischemic heart failure. The advances and
      the need for further studies to establish both the natural history of such
      ventricular dysfunction and the role of coronary revascularization are discussed.

PMID- 11251128
TI  - The identification of myocardial hibernation in patients with ischemic heart
      failure by echocardiography and radionuclide studies.
AB  - Dobutamine echocardiography and myocardial radionuclide tomography are widely
      used to assess viability in patients with ischemic cardiomyopathy and left
      ventricular dysfunction. The main goal of viability evaluation has been the
      identification of reversible regional dysfunction in the attempt to identify
      patients in whom revascularization may determine an improvement of global left
      ventricular ejection fraction. In this application, echocardiographic and
      radionuclide techniques are used to characterize different pathophysiologic
      aspects of viable myocardium, ie, integrity of cell membrane and contractile
      reserve. This explains why the information of the 2 techniques are often
      divergent and why radionuclide techniques have the highest sensitivity but
      reduced specificity compared with echocardiography for predicting recovery of
      regional dysfunction. The identification of residual viable myocardium by either
      technique is strongly associated with adverse prognosis if the patients are not
      revascularized, and this substantially contributes to the decision-making process
      in individual patients. Although it has been assumed that prognostic advantages
      of revascularization are linked to an increase of ejection fraction,
      pathophysiologic and clinical observations challenge us with the possibility that
      benefits of revascularization may also ensue independently on the recovery of
      ejection fraction through alternative pathophysiologic mechanisms. Therefore,
      clinical application of viability tests should be evaluated against relevant
      endpoints, mainly represented by prolongation of life and improvement of life
      quality, and not by surrogate endpoints as represented by recovery of global
      ejection fraction. Future studies are needed to assess whether a more clinically
      oriented approach will provide a better selection of patient candidates for
      revascularization.

PMID- 11251129
TI  - What is the optimal medical management of ischemic heart failure?
AB  - Ischemic heart disease is an important and common contributor to the development
      of heart failure. Theoretically, all patients with heart failure may benefit from
      treatment designed to retard progressive ventricular dysfunction and arrhythmias.
      Patients with ischemic heart disease may also theoretically benefit from the
      relief of ischemia, the prevention of coronary occlusion, and revascularization.
      However, there is little evidence to show that the presence or absence of
      coronary disease modifies the benefits of effective treatments such as
      angiotensin-converting enzyme inhibitors and beta-blockers. Moreover, there is no
      evidence that treatment directed specifically at myocardial ischemia or coronary
      disease alters outcome in patients with heart failure. Treatments aimed at
      relieving painless myocardial ischemia have not been shown to alter prognosis.
      Lipid-lowering therapy is theoretically attractive for patients with heart
      failure and coronary disease; however, theoretical concerns also exist about the
      safety of such agents, and patients with heart failure have been excluded from
      large outcome studies very effectively. Some agents, such as aspirin, designed to
      reduce the risk of coronary occlusion seem ineffective or harmful in patients
      with heart failure, although warfarin may be safe and possibly effective. There
      is no evidence yet that revascularization improves prognosis in patients with
      heart failure, even in patients who are shown to have extensive myocardial
      hibernation. On current evidence, revascularization should be reserved for the
      relief of angina. Large-scale, randomized controlled trials are currently
      underway that are investigating the role of specific treatments targeted at
      coronary syndromes. The Carvedilol Hibernation Reversible Ischemia Trial: Marker
      of Success study is investigating the effects of carvedilol in a large cohort of
      patients with and without hibernating myocardium. The Warfarin and Antiplatelet
      Therapy in Chronic Heart Failure study is comparing the efficacy of aspirin,
      clopidogrel, and warfarin. The Heart Revascularization Trial-United Kingdom study
      is assessing the effect of revascularization on mortality in patients with heart
      failure and myocardial hibernation. Smaller scale studies are assessing the
      safety and efficacy of statin therapy in patients with heart failure. Only once
      the outcomes to these and other planned trials are known can the medical
      community know how best to treat their patients.

PMID- 11251130
TI  - How close is close enough? Defining the "paresthesia chad".

PMID- 11251131
TI  - What is the relationship between paresthesia and nerve stimulation for axillary
      brachial plexus block?
AB  - BACKGROUND AND OBJECTIVES: To quantify the motor threshold current of a needle
      following elicitation of paresthesia during axillary brachial plexus block
      (ABPB). METHODS: This is a prospective, observational study of ABPB in 72
      patients. Having elicited paresthesia, the minimum current required to produce a
      motor response was noted. The development and success of the block were
      subsequently followed. RESULTS: Nineteen blocks were excluded (18 because of
      arterial puncture and 1 blocked needle). Of the remaining 53 blocks, 41 (77%)
      produced a motor response at 0.5 mA or less. The median current was 0.17 mA
      (range, 0.03 to 3.3 mA). The site of initial paresthesia and subsequent motor
      response were related in 43 (81%) of cases. CONCLUSIONS: A needle position
      causing paresthesia produced a motor response at 0.5 mA or less in 77% of cases
      studied. This current may, therefore, be a reasonable threshold to aim for when
      performing an ABPB.

PMID- 11251132
TI  - Hypotensive epidural anesthesia in total knee replacement without tourniquet:
      reduced blood loss and transfusion.
AB  - BACKGROUND AND OBJECTIVES: [corrected] For decades, hypotensive anesthesia has
      been used in an attempt to reduce intraoperative blood loss. Hypotensive epidural
      anesthesia (HEA) is a relatively new technique in hypotensive anesthesia. Use of
      a tourniquet has been shown to be associated with a higher risk of cardiovascular
      and thromboembolic complications. The effect of HEA on blood loss and need for
      transfusion in total knee replacement (TKR) is not known. METHODS: Thirty
      consecutive patients scheduled for TKR were randomized to HEA without tourniquet
      or spinal anesthesia with the use of a tourniquet (SPI). HEA was performed as an
      epidurally induced sympathetic block and there was an infusion of low-dose
      epinephrine to stabilize the circulation. RESULTS: Intraoperative mean arterial
      blood pressure was 48 mm Hg (HEA) versus 83 mm Hg (SPI) (P <.001). Intraoperative
      blood loss was 146 mL (HEA) versus 13 mL (SPI) (P <.001). Postoperative blood
      loss at any time was significantly reduced in the HEA group, and total loss of
      blood was 1,056 mL (HEA) versus 1,826 mL (SPI) (P <.001). Half of the bleeding
      took place during the first 3 postoperative hours and 80% during the first 24
      hours. In the HEA group, 57% of the patients went through surgery and the
      hospital stay without receiving blood transfusion versus 19% in the SPI group (P
      <.05). There was a significantly reduced amount of blood transfusion in the HEA
      group (193 mL) versus 775 mL in the SPI group (P <.005). No cardiopulmonary,
      cerebral, or renal complications were registered. CONCLUSIONS: We conclude that
      HEA is a safe technique that allows TKR without a tourniquet. Compared with
      spinal anesthesia, the use of HEA for TKR significantly reduces blood loss and
      the need for blood transfusion.

PMID- 11251133
TI  - Epidural analgesia and risk of anastomotic leakage.
AB  - BACKGROUND AND OBJECTIVES: Based on case reports of early anastomotic leakage in
      patients receiving epidural analgesia with local anesthetic and data to document
      a stimulatory effect of epidural block on gastrointestinal motility, it has been
      suggested that continuous infusion of epidural local anesthetic may lead to an
      increased incidence of anastomotic leakage. Therefore, we examined the
      association between continuous epidural local anesthetic and anastomotic leakage
      by reviewing the literature. METHODS: Review of controlled, randomized clinical
      trials aiming to investigate postoperative complications in which continuous
      postoperative epidural local anesthetic was administered in patients scheduled
      for colorectal surgery with an anastomosis. Data were obtained from a Medline
      search (1966-May 2000), previous review articles, references cited in original
      papers, and personal communication with investigators. Twelve trials including a
      total of 562 patients met the inclusion criteria. RESULTS: Sixteen of 266
      patients (6.0%, 95% confidence interval [CI]: 3.5% to 9.6%) receiving
      postoperative epidural local anesthetic or epidural local anesthetic-opioid
      mixtures developed anastomotic leakage, compared with 10 of 296 patients (3.4%,
      95% CI: 1.6% to 6.1%) receiving epidural or systemic opioid-based analgesia (P
      >.05 between groups, Fisher's test). The risk of overlooking a significant
      difference (type II error) was approximately 67% (power: 33%). Studies including
      more than 1,037 patients in each group are needed to demonstrate an increased
      risk of anastomotic leakage from 3.4% to 6.0% with 80% power and 2alpha = 0.05.
      There was no significant difference (P >.05 between groups, Fisher's test)
      between subgroups of study design: Epidural local anesthetic-versus systemic or
      epidural opioid, or epidural local anesthetic-opioid mixtures versus systemic or
      epidural opioid. CONCLUSIONS: So far, there is no statistically significant
      evidence from randomized trials to indicate epidural analgesia with local
      anesthetic to be associated with an increased risk of anastomotic breakdown.
      However, relatively few patients have been included in randomized trials,
      indicating a need for more studies to secure valid conclusions.

PMID- 11251134
TI  - Efficacy and safety of dipyrone versus tramadol in the management of pain after
      hysterectomy: a randomized, double-blind, multicenter study.
AB  - BACKGROUND AND OBJECTIVES: We assessed the efficacy and safety of dipyrone in
      comparison with tramadol in the relief of early postoperative pain following
      abdominal hysterectomy. METHODS: A total of 151 women between 18 and 60 years of
      age undergoing abdominal hysterectomy during general anesthesia participated in a
      randomized, double-blind, controlled, multicenter study. Seventy-three patients
      received dipyrone and 78 received tramadol. Patients received an intravenous
      loading dose of the study drug immediately after operation followed by
      intravenous (IV) maintenance infusion and IV on-demand boluses up to a maximum
      number of predetermined doses/day of 8 g dipyrone and 500 mg tramadol. The
      duration of the study was 24 hours. RESULTS: The mean (SD) number of boluses in
      the dipyrone group was 3.8 (2.4) and 3.5 (2.5) in the tramadol group (95%
      confidence interval, -0.455 to 1.175), and the percentage of patients requiring
      rescue IV morphine (dipyrone 26.9%, tramadol 26.8%) was not statistically
      significant. Other analgesic efficacy parameters, such as pain intensity
      differences, sum of pain intensity differences, pain relief assessed by the
      patient, or patients who required the maximum number of demand doses, were not
      different between treatment groups. A significantly higher percentage of adverse
      gastrointestinal effects was found in patients given tramadol (42.1%) than in
      patients given dipyrone (20.2%) (P <.05). Also, a significantly higher number of
      tramadol-treated patients required ondansetron to control nausea and vomiting at
      1 hour (19% v 7%), 2 hours (26% v 11%), and 24 hours (46% v 29%) (P <.05) after
      surgery. Patients and the investigators reported similar tolerability for both
      study arms. CONCLUSIONS: Dipyrone and tramadol showed similar efficacy for early
      pain relief after abdominal hysterectomy. Nausea and vomiting, possibly caused by
      the tramadol, occurred more frequently in those patients. In this group, the need
      of the antiemetic drug ondansetron was also higher.

PMID- 11251135
TI  - Effect of preemptive multimodal analgesia for arthroscopic knee ligament repair.
AB  - BACKGROUND AND OBJECTIVES: Administration of analgesic medication before surgery,
      rather than at the completion of the procedure, may reduce postoperative pain.
      Similarly, administration of multiple analgesics, with different mechanisms of
      action, may provide improved postoperative pain control and functional recovery.
      The purpose of our study was to compare pain scores and intravenous opioid
      consumption after outpatient anterior cruciate ligament (ACL) reconstruction in
      patients who received a multimodal drug combination (intravenous [IV] ketorolac,
      intra-articular morphine/ropivacaine/epinephrine, and femoral nerve block with
      ropivacaine) either before surgery or immediately at the completion of the
      surgical procedure. METHODS: Forty patients presenting for same-day arthroscopic
      ACL repair using a semitendinosis tendon graft were included in this study. The
      patients were randomized to receive the following drugs either 15 minutes before
      skin incision or immediately after skin closure: (1) Ketorolac 30 mg IV. (2)
      Intra-articular injection of 20 mL ropivacaine 0.25% + morphine 2 mg and
      epinephrine 1:200,000. (3) Femoral nerve block with 20 mL ropivacaine 0.25%.
      Verbal pain scores were obtained in the postanesthesia care unit (PACU) and on
      postoperative days 1, 3, and 7. IV patient controlled analgesia (PCA) morphine
      consumption in the PACU was also recorded. RESULTS: Verbal pain rating scores
      were lower in group I (preemptive) for 2.0 hours after arrival in the PACU. There
      was no difference between groups in pain scores on postoperative days 1, 3, and
      7. Mean IV PCA morphine consumption in the PACU was lower in group I (6.4 mg)
      versus group II (12.3 mg), P <.05. CONCLUSION: Preemptive, multimodal
      administration of our 3-component analgesic drug combination resulted in lower
      pain scores during the initial stay in the PACU unit and lower consumption of IV
      PCA morphine in the PACU. However, pain scores were similar in both groups on
      postoperative days 1, 3, and 7; thus, there was no measurable long-term advantage
      associated with preemptive multimodal drug administration.

PMID- 11251136
TI  - Assessment of wound infiltration with bupivacaine in women undergoing day-case
      gynecological laparoscopy.
AB  - BACKGROUND AND OBJECTIVES: The effectiveness of local anesthetic wound
      infiltration for treatment of postoperative pain appears to be variable and
      partly dependent on the surgical procedure. Although evidence was lacking, it was
      common practice at our institution to infiltrate the trocar wound of patients
      undergoing day-case laparoscopic procedures with long acting local anesthetic
      agents. The aim of this study was to investigate the analgesic efficacy, and the
      influence of the timing, of local anesthetic infiltration into surgical wounds
      for day-case diagnostic gynecological laparoscopy. METHODS: A double-blind,
      randomized trial was conducted on 100 women having general anesthesia for day
      case gynecological laparoscopy. Ninety-two patients who had been randomized to 1
      of 4 groups for trocar wound infiltration with 30 mL of 0.25% bupivacaine or
      saline either before or after surgery completed the study. Incisional pain, pain
      on pressing the umbilicus, severity of nausea, and patient satisfaction with
      anesthetic technique were all assessed postoperatively until discharge and on the
      following day through a telephone interview. A P value of <.05 was considered
      significant. RESULTS: There was no difference between groups in the mean pain
      scores or analgesic requirements for incisional pain, pain on pressing firmly on
      the umbilicus, or for patient satisfaction. There was a trend for those patients
      who had received bupivacaine to use less postoperative morphine (P =.079).
      CONCLUSIONS: Wound infiltration with local anaesthetic did not significantly
      reduce pain or opioid requirement after gynecological laparoscopy.

PMID- 11251137
TI  - Radiofrequency sacroiliac joint denervation for sacroiliac syndrome.
AB  - BACKGROUND AND OBJECTIVES: Radiofrequency (RF) denervation of the sacroiliac (SI)
      joint has been advocated for the treatment of sacroiliac syndrome, yet no
      clinical studies or case series support its use. METHODS: We report the results
      of a consecutive series of 50 SI joint RF denervations performed in 33 patients
      with sacroiliac syndrome. All patients underwent diagnostic SI joint injections
      with local anesthetic before denervation. Changes in visual analog pain scores
      (VAS), pain diagrams, physical examination (palpation tenderness over the joint,
      myofascial trigger points overlying the joint, SI joint pain provocation tests,
      and range of motion of the lumbar spine), and opioid use were assessed pre- and
      postdenervation. RESULTS: The criteria for successful RF denervation were at
      least a 50% decrease in VAS for a period of at least 6 months; 36.4% of patients
      (12 of 33) met these criteria. Failure of denervation correlated with the
      presence of disability determination and pain on lateral flexion to the affected
      side. The average duration of pain relief was 12.0 +/- 1.2 months in responders
      versus 0.9 +/- 0.2 months in nonresponders (P < or = 0.0001). A positive response
      was associated with an atraumatic inciting event. Successful denervation was
      associated with a change in the pain diagram and a reduction in the pattern of
      referred pain, a normalization of SI joint pain provocation tests, and a
      reduction in the use of opioids. CONCLUSIONS: This study suggests that RF
      denervation of the SI joint can significantly reduce pain in selected patients
      with sacroiliac syndrome for a protracted time period. Moreover, certain abnormal
      physical findings (i.e., SI joint pain provocation tests) revert to normal for
      the duration of the analgesia.

PMID- 11251138
TI  - Prospective experience with a 20-gauge Tuohy needle for lumbar epidural steroid
      injections: Is confirmation with fluoroscopy necessary?
AB  - BACKGROUND AND OBJECTIVES: Small (20-gauge) Tuohy needles have been introduced
      for epidural steroid injection to optimize patient comfort and decrease the risk
      of spinal headache. These needles may be less reliable for indentification of the
      epidural space than standard 17- or 18-gauge needles because of their small size.
      We prospectively examined the success rate of lumbar epidural steroid placement
      with loss-of-resistance (LOR) technique compared with fluoroscopy confirmation.
      METHODS: One hundred patients without history of lumbar spine surgery were
      enrolled. A 20-gauge Tuohy needle was placed into the epidural space using LOR to
      saline. Confidence in epidural placement was recorded (Yes/No). Radiologic
      contrast was then injected and a fluoroscopic epidurogram interpreted by a
      blinded radiologist for correct placement, (Yes/No) separate from the clinical
      process. RESULTS: Reliability of LOR was less than our "gold standard" of
      fluoroscopy (P <.004). Sensitivity of LOR was 99% and specificity was 27%.
      Positive and negative predictive values were 92% and 75%. Increased patient age
      (>70 years) and male sex were associated with poor reliability of LOR (P <.05).
      CONCLUSIONS: In contrast to the reported 99% success rates for epidural placement
      of standard 17- or 18-gauge Tuohy needles, we observed a success rate of 92%.
      Small-gauge Tuohy needles are technically more difficult to use than larger
      needles and may require confirmation with fluoroscopy for correct epidural
      placement, especially in elderly male patients.

PMID- 11251139
TI  - Diagnostic lumbosacral segmental nerve blocks with local anesthetics: a
      prospective double-blind study on the variability and interpretation of segmental
      effects.
AB  - BACKGROUND AND OBJECTIVES: Selective spinal nerve infiltration blocks are used
      diagnostically in patients with chronic low back pain radiating into the leg.
      Generally, a segmental nerve block is considered successful if the pain is
      reduced substantially. Hypesthesia and elicited paresthesias coinciding with the
      presumed segmental level are used as controls. The interpretation depends on a
      standard dermatomal map. However, it is not clear if this interpretation is
      reliable enough, because standard dermatomal maps do not show the overlap of
      neighboring dermatomes. The goal of the present study is to establish if
      dissimilarities exist between areas of hypesthesia, spontaneous pain reported by
      the patient, pain reduction by local anesthetics, and paresthesias elicited by
      sensory electrostimulation. A secondary goal is to determine to what extent the
      interpretation is improved when the overlaps of neighboring dermatomes are taken
      into account. METHODS: Patients suffering from chronic low back pain with pain
      radiating into the leg underwent lumbosacral segmental nerve root blocks at
      subsequent levels on separate days. Lidocaine (2%, 0.5 mL) mixed with radiopaque
      fluid (0.25 mL) was injected after verifying the target location using sensory
      and motor electrostimulation. Sensory changes (pinprick method), paresthesias
      (reported by the patient), and pain reduction (Numeric Rating Scale) were
      reported. Hypesthesia and paresthesias were registered in a standard dermatomal
      map and in an adapted map which included overlap of neighboring dermatomes. The
      relationships between spinal level of injection, extent of hypesthesia, location
      of paresthesias, and corresponding dermatome were assessed quantitatively.
      Comparison of the results between both dermatomal maps was done by paired t
      tests. RESULTS: After inclusion, data were processed for 40 segmental nerve
      blocks (L2-S1) performed in 29 patients. Pain reduction was achieved in 43%.
      Hypesthetic areas showed a large variability in size and location, and also in
      comparison to paresthesias. Mean hypesthetic area amounted 2.7 +/- 1.4 (+/- SD:
      range, 0 to 6; standard map) and 3.6 +/- 1.8 (0 to 6; adapted map; P <.001)
      dermatomes. In these cases, hypesthesia in the corresponding dermatome was found
      in 80% (standard map) and 88% of the cases (adapted map, not significant).
      Paresthesias occurring in the corresponding dermatome were found in 80% (standard
      map) compared with 98% (adapted map, P <.001). In 85% (standard map) and 88%
      (adapted map), spontaneous pain was present in the dermatome corresponding to the
      level of local anesthetic injection. In 55% (standard map) versus 75% (adapted
      map, P <.005), a combination of spontaneous pain, hypesthesia, and paresthesias
      was found in the corresponding dermatome. CONCLUSIONS: Hypesthetic areas
      determined after lumbosacral segmental nerve blocks show a large variability in
      size and location compared with elicited paresthesias. Confirmation of an
      adequately performed segmental nerve block, determined by coexistence of
      hypesthesia, elicited paresthesias and pain in the presumed dermatome, is more
      reliable when the overlap of neighboring dermatomes is taken into account.

PMID- 11251140
TI  - The effect of nonsteroidal anti-inflammatory drugs on osteogenesis and spinal
      fusion.

PMID- 11251142
TI  - An introduction to digital cameras.
AB  - BACKGROUND AND OBJECTIVES: People in all walks of life are using digital cameras
      instead of the traditional film cameras. Reasons include simplicity of use, ease
      of development, ability to incorporate the pictures into documents, potential to
      edit the pictures easily, and capability to send them by e-mail. This article
      will briefly discuss digital cameras, how they work, what they can do, and what
      you should look for in one. Editor's Note: This is the fourth in a series of
      articles demonstrating and describing information technology. The articles
      include nontechnical information and are geared toward the computer novice with
      interest in regional anesthesia and pain medicine.

PMID- 11251143
TI  - Thoracic paravertebral block for management of pain associated with multiple
      fractured ribs in patients with concomitant lumbar spinal trauma.
AB  - BACKGROUND AND OBJECTIVES: The need for continual neurological assessment in
      patients with lumbar spinal injury poses a challenge for effective management of
      pain associated with multiple fractured ribs. Two cases are presented to
      illustrate the benefits of using thoracic paravertebral block to control the pain
      of multiple fractured ribs without compromising the ongoing neurological
      assessment. CASE REPORT: Thoracic paravertebral block was used in 2 patients with
      concomitant multiple fractured ribs and lumbar spinal injury. Case 2 also had a
      head injury and there was moderate coagulopathy. The thoracic paravertebral
      catheter was placed in the upper thoracic region and radiological imaging was
      used to delineate spread before the injection of relatively small volumes (10 to
      15 mL) of local anesthetic. In case 1, the thoracic paravertebral block produced
      ipsilateral segmental thoracic anesthesia, providing excellent pain relief for
      the fractured ribs. It also spared the lumbar and sacral nerve roots, preserving
      neurological function in the lower extremities and bladder sensation. In case 2,
      effective analgesia without systemic sedation and opioids resulted in the patient
      regaining consciousness, which allowed continuous assessment of central and
      peripheral neurological function. CONCLUSION: Thoracic paravertebral block is an
      option for managing pain associated with multiple fractured ribs in the presence
      of concomitant lumbar spinal injury requiring continual neurological assessment.

PMID- 11251141
TI  - Endoscopic technique with ultrasound imaging for neurolytic celiac plexus block.

PMID- 11251144
TI  - Combined spinal and epidural anesthesia for labor and cesarean delivery in a
      patient with Guillain-Barre syndrome.
AB  - BACKGROUND AND OBJECTIVES: The anesthetic management of labor, delivery, and
      cesarean delivery in patients with active or resolving Guillain-Barre syndrome is
      not well defined. Using a combined spinal and epidural (CSE) technique in such a
      rare clinical situation has not been previously reported. CASE REPORT: A 32-year
      old woman gravida 2, para 0 was diagnosed with Guillain-Barre syndrome at 21
      weeks of pregnancy. Paralysis spread up to the T4 level. Three months later, she
      was admitted for labor at term. She presented in severe labor pain and it was
      decided to proceed with CSE analgesia. No unusual hemodynamic instability, signs
      of autonomic dysfunction, or increased sensitivity to local anesthetics was
      noted. After several hours, delivery by cesarean section was required and
      epidural anesthesia was then used. The patient had an uncomplicated postpartum
      course. CONCLUSION: Careful evaluation and documentation of the patient's
      baseline neurological status, a thorough discussion with the patient regarding
      the risks and benefits of the technique for labor analgesia, and an appreciation
      of the limited experience with this kind of clinical situation are important.

PMID- 11251145
TI  - Limiting transient radicular irritation.

PMID- 11251147
TI  - Transient neurologic syndrome, transient radicular irritation, or postspinal
      musculoskeletal symptoms: Are we describing the same "syndrome" in all patients?

PMID- 11251150
TI  - Low-dose spinal anesthesia for cesarean delivery: Have we gone too far?

PMID- 11251153
TI  - Postdural/arachnoid puncture headache.

PMID- 11251155
TI  - Is a deltoid twitch a satisfactory endpoint for all interscalene blocks?

PMID- 11251156
TI  - Is a deltoid twitch a satisfactory endpoint for all interscalene blocks?

PMID- 11251158
TI  - Forefoot surgery with ankle tourniquet: complete or selective ankle block?

PMID- 11251159
TI  - Use of near-infrared spectroscopy to evaluate stellate ganglion block.

PMID- 11251160
TI  - Synthesis and degradation of basement membranes and extracellular matrix and
      their regulation by TGF-beta in invasive carcinomas (Review).
AB  - The proper structure of the extracellular matrix, in particular of the basement
      membrane and the adjacent interstitial matrix, are essential prerequisites for a
      proper function of tissues. Invasive growth in malignant tumors is associated
      with a destruction of various matrix structures. Due to extensive recent analyses
      significant advances have been made in the knowledge of the structure of the
      extracellular matrix, the composition of its most important constituents, their
      metabolism and that of matrix degrading enzymes. This information provides
      insight into the pathophysiology of malignant growth. Thereby, it has been shown
      that malignant tumor growth is associated with a loss of basement membrane (BM)
      material which, however, disappears not homogeneously, but affects various BM
      components to different degree. The loss of an intact BM as the first barrier is
      therefore the initial step of tumor invasion. Despite this loss there is evidence
      that the de novo synthesis of BM constituents in tumor and adjacent stromal cells
      is enhanced. Thus, it is obvious that BM material is degraded during the invasion
      process to significant degree. In addition, since there is a positive correlation
      between the amount of retained peritumoral BM and a higher degree of tumor cell
      differentiation the amount of retained BM material seems to represent a marker
      for the biological behaviour of the tumor cells. The loss of BM material is well
      explained by a significant expression of major matrix degrading enzymes, the
      matrix metalloproteinases (MMPs) both on the mRNA and protein level. Here again,
      there is considerable data indicating that both tumor and stroma cells are
      involved in the MMP synthesis. In addition to the loss of BM substances, the
      interstitial extracellular matrix (ECM) is disarranged. This disarrangement may
      comprise enhanced de novo synthesis ("desmoplasia") or dissolution by distinct
      MMPs (collagenases, such as MMP-1) reflecting obviously different reaction
      statuses of the stromal cells. Finally, significant work has been done on the
      elucidation of the role of regulating cytokine systems. To this regard,
      particular attention has been paid to the TGF-beta system and it has been shown
      that the major three isoforms of TGF-betas are upregulated both in tumor and
      stroma cells. Since the TGF-beta-effect is mainly mediated by a particular
      signalling system via the TGF-beta-receptors (TBRs), the investigation of this
      system has provided considerable insight into the role of TBRs which are now
      known to represent the most potent tumor suppressor genes. Thus frequent
      mutations in the TBR-II gene, one of the three TBRs, in various carcinomas
      suggest that these molecular alterations are responsible for both the loss of the
      control of cellular proliferation (in tumor cells) and altered matrix metabolism
      (in tumor and stroma cells). The further analysis of this major cytokine system
      therefore will provide us with major insights into the molecular abnormalities of
      invasive tumor growth.

PMID- 11251161
TI  - Insulin and cancer (Review).
AB  - Although the molecular mechanisms of insulin action on many physiological and
      biochemical processes are far from being completely understood, little doubt
      exists about the involvement of insulin in tumoural processes. Indeed, increased
      insulin production (either directly by the tumour in an ectopic fashion, or
      indirectly by stimulation of the pancreatic secretion) is a common phenomenon
      during cancer development. Paradoxically, the increased production and
      circulating levels of the hormone are associated with a decrease in sensitivity
      which leads to insulin resistance in the non-tumoural tissues, resulting in
      hyperlipaemia and profound alterations in carbohydrate and lipid metabolism. In
      addition to these effects on the host, insulin can actually increase the
      incidence of neoplasias and promote tumour growth. This is probably related to
      the signaling pathway of the hormone, which shares many elements with that of
      several growth factors. In addition, insulin signaling directly interacts with
      that of the ras oncogene. We review the involvement of insulin in cancer from a
      multidisciplinary point of view, with the aim of encouraging the design of future
      therapeutic options for cancer treatment.

PMID- 11251162
TI  - The clavicle: a vulnerable bone in pediatric oncology.
AB  - The clavicle is frequently incorporated into the radiation field in the treatment
      of malignant tumors located in the head and neck. From 1954 to 1995, 499
      pediatric patients were treated with moderate to high-dose radiation therapy to
      the head and neck at the University of Texas M.D. Anderson Cancer Center. The
      medical records of 312 of these patients were available and were reviewed. The
      period of observation ranged from 5 to 30 years. Five late radiation-induced
      abnormalities of the clavicle were encountered: osteosarcoma; osteochondroma;
      malignant fibrous histiocytoma; radionecrosis and impaired healing following
      trauma and radionecrosis and lysis. The doses of radiation therapy which induced
      the abnormalities varied from 35 to 60.5 Gy (median 34.75 Gy). The interval from
      radiation therapy to discovery of the complications varied from 6 to 11 years.
      Two patients died: one from malignant fibrous histiocytoma and another from a
      radiation-induced meningioma of the brain (which accompanied radionecrosis of the
      clavicle). We conclude that the incidence of radiation-induced abnormalities of
      the clavicle in pediatric long-term survivors is low (1.5%). However, some of the
      late sequela are potentially fatal. The clavicle should be considered a
      vulnerable bone to radiation therapy and should be monitored in long-term
      survivors of childhood cancer. The experience is compared to radiation-induced
      abnormalities recorded in the literature.

PMID- 11251163
TI  - Resistance to growth inhibitory and apoptotic effects of phorbol ester and UCN-01
      in aggressive cancer cell lines.
AB  - 7-Hydroxystaurosporine (UCN-01), a non-selective inhibitor of protein kinase C
      (PKC), and phorbol ester (PMA), a PKC activator, are undergoing clinical
      evaluations. We investigated the effects of UCN-01 and PMA on a panel of prostate
      cancer cell lines. While PMA induced p21WAF1/CIP1 and arrest growth of LNCaP
      cancer cells (IC50 = 0.5-1 nM), aggressive cancer cell lines (DU145, PC3, and
      PC3M) were resistant to PMA (IC50 >5000 nM). Low concentrations (25-50 nM) of UCN
      01 abrogated PMA-induced p21 and growth arrest in LNCaP cells. These low doses of
      UCN-01 however did not inhibit proliferation of any prostate cancer cell line.
      PMA-sensitive LNCaP cells were resistant to clinically relevant concentrations of
      UCN-01 (IC50 = 1.2 microM), but UCN-01 inhibited growth of DU145 and PC3/3M with
      an IC50 of 200-400 nM. For comparison, PMA-sensitive HL60 leukemia cells were
      sensitive to UCN-01 due to rapid apoptosis caused by UCN-01. In PMA-resistant
      prostate cancer cells, UCN-01 downregulated cyclin D1, induced p21, caused
      morphological differentiation, and G1-phase arrest leading to slow cell death
      without caspase activation. Importantly, normal prostate epithelial cells (PrEC)
      were very sensitive to both PMA (IC50 = 0.2 nM) and UCN-01. In PrEC, UCN-01
      downregulated cyclin D1 and arrest growth with an IC50 less than 100 nM. We
      conclude that loss of sensitivity to either UCN-01 or PMA accompanies progression
      of prostate cancer.

PMID- 11251164
TI  - Discrepancies between the gene expression, protein expression, and enzymatic
      activity of thymidylate synthase and dihydropyrimidine dehydrogenase in human
      gastrointestinal cancers and adjacent normal mucosa.
AB  - The relationships between gene expression, protein expression, and enzymatic
      activity of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD)
      have not been clarified in tumor and non-tumor tissues of human. In this study,
      we compared three different parameters by evaluating TS and DPD levels, mRNA
      expression assessed by RT-PCR, protein expression evaluated by
      immunohistochemical examination, and enzymatic activity measured by biochemical
      assay, in the tumor tissue and adjacent normal mucosa of 43 patients with
      gastrointestinal cancer. TS enzymatic activity in the tumor tissue was
      significantly higher than in normal tissue in both the stomach (median activity:
      81.0 and 38.0 pmol/mg protein, respectively, p=0.012) and the colorectum (49.8
      and 30.8, respectively, p=0.023). Similarly, TS mRNA expression in the tumor
      tissue was significantly higher than in normal tissue in both the stomach (median
      TS/GAPDH ratio: 6.0 and 2.0, respectively, p=0.009) and the colorectum (3.20 and
      0.91, respectively, p=0.001). But no significant differences in DPD activity were
      observed between the tumor and normal tissue in either stomach (median activity:
      41.3 and 41.6 pmol/min/mg protein, respectively) or colorectum (34.9 and 49.0,
      respectively). On the other hand, DPD mRNA levels in normal tissue were
      significantly higher than in tumor tissue only in the colorectum (DPD/GAPDH
      ratio: 0.83 and 0.20, respectively, p=0.003). No linear relationships were found
      between the enzymatic activity and mRNA expression of TS or DPD either in tumor
      or normal tissue. Nor were any correlations found between protein expression and
      either mRNA expression or enzymatic activity for either TS or DPD. These results
      suggest that tissue TS and DPD levels may vary with differences in the methods
      used to measure them. These discrepancies must be taken into account when
      interpreting correlation between TS and DPD levels and clinical outcome.

PMID- 11251165
TI  - Increased expression of S100A4 and its prognostic significance in esophageal
      squamous cell carcinoma.
AB  - S100A4 has been implicated in invasion and metastasis of cancer, but prognostic
      significance of its expression in esophageal squamous cell carcinoma remains
      unclear. In this study, we examined the expression of S100A4 by Western blot
      analysis and immunohistochemistry in surgically resected esophageal squamous cell
      carcinoma. The relationship between S100A4 tissue status and clinicopathological
      findings was analyzed to assess the prognostic significance of S100A4 in
      esophageal squamous cell carcinoma. The S100A4 protein level was significantly
      higher in tumor tissue than in corresponding normal esophageal mucosa (p<0.05) in
      22 cases of esophageal carcinoma by Western blot analysis. S100A4 expression was
      detected in 25% of 52 cases of esophageal squamous cell carcinoma by
      immunohistochemistry and correlated with the depth of invasion (p<0.05). Patients
      with S100A4-positive carcinoma had significantly poorer prognosis than those with
      S100A4-negative carcinoma, which was also true in the cases with deep invasion of
      the primary cancer (T3, T4) (p<0.01 and p<0.05, respectively). Moreover, S100A4
      tissue status remained the only independent prognostic parameter in the
      multivariate analysis. Our results suggest that S100A4 may play a key role in the
      progression of esophageal carcinoma and that immunohistochemical detection of
      S100A4 in the primary tumor may be useful for the prediction of a poor prognosis.

PMID- 11251166
TI  - The invasive features of glial and non-central nervous system tumor cells are
      different on organotypic brain slices from newborn rats.
AB  - On radiograms, glial tumors are usually seen to invade in a finger-like fashion,
      while non-central nervous system (CNS) tumors expand in a mass-like fashion. We
      prepared organotypic brain slice cultures from newborn rats to investigate the
      invasive behavior of human brain tumors using glial tumor cell lines (U-87MG, U
      373MG, U-251MG, and SF-126) and of non-CNS tumors using cell lines; HT-1080
      (human malignant fibrosarcoma), RFRF (human lung carcinoma), MIA-PICA (human
      pancreatic carcinoma), and Colo38 (human malignant melanoma). We selected an area
      that was centered at a junction between deep cortical layers and the striatum,
      punched a hole measuring 0.5-0.7 mm in diameter in this area, implanted different
      rhodamine-labeled tumor cells at that site, and observed their invasive behavior
      under an inverted fluorescent microscope. Over the course of several days, all
      glioma cells invaded in a finger-like fashion; U-373 MG cells invaded farthest.
      Non-CNS tumors expanded in mass-like fashion into adjacent areas. Using the slice
      cultures, we also investigated the regulatory effect on tumor invasion of forced
      expression of glial fibrillary acidic protein (GFAP) after gene transfection. The
      forced expression of GFAP rendered U-87MG and HT-1080 cells less invasive. Our
      results show that organotypic brain slice cultures are an excellent medium for
      studying the invasive features of glial and non-CNS tumors.

PMID- 11251167
TI  - Establishment and characterization of a cell line (T201) derived from a human
      larynx squamous cell carcinoma.
AB  - The purpose of this report was the initiation and further maintenance of tumor
      cells from a primary larynx squamous cell carcinoma. A tumor fragment was
      mechanically dissociated, the cells were grown in RPMI medium, being the primary
      culture dependent on the presence of epidermal growth factor and insulin; during
      subsequent passages the adaptation to conventional growth conditions was
      obtained. Cells grew in monolayer with an epitheliod shape, showing a pavement
      like arrangement; at confluence, cells piled up without contact inhibition
      maintaining the same morphology. Population doubling time was about 48 h with a
      colony-forming efficiency of 10%. Immunocytochemical characterization was
      performed with a panel of monoclonal antibodies reactive against tumor associated
      antigens, including mucin glycoproteins and related carbohydrate antigens,
      carcinoembryonic antigen (CEA), p53 as well as cytokeratins, vimentin and desmin.
      T201 expressed CEA, sialyl Lewis x, Lewis x, Lewis y, MUC1 mucin, Tn hapten, p53,
      vimentin and cytokeratins. On the other hand, a modal chromosome diploid number
      of 46 occurring in 74% of cells was detected. Present data confirmed that the
      methodology employed was adequate for the establishment and characterization of a
      new cell line which can provide a useful model to study biological and
      immunological aspects of larynx squamous cell carcinoma.

PMID- 11251169
TI  - Localised extranodal non-Hodgkin's lymphoma of the gastrointestinal tract:
      Sheffield Lymphoma Group experience (1989-1998).
AB  - Extranodal non-Hodgkin's lymphoma (NHL) of the gastrointestinal tract accounts
      for about one third of all extranodal NHL. We retrospectively reviewed the
      clinical and histopathologic records of 71 patients with stage IE and IIE primary
      gastrointestinal NHL referred to the Sheffield Lymphoma Group (SLG) from 1989 to
      1998. Cross-referencing with the Hospital Histopathology Department database
      revealed that only two-thirds of all cases were seen by the Group. The most
      common primary site was the stomach (45 patients, 63% of all cases), followed by
      the small intestine (16, 23%) and large intestine (9, 13%). The median age of
      patients was 62 years; the majority of patients presented with stage I (61%)
      and/or grade (65%) NHL. Mucosa-associated lymphoid tissue (MALT) lymphomas were
      the largest histologic subtype seen (57%), with 87% of these arising from the
      stomach; next most frequent was the diffuse large B-cell subtype (21% of all
      cases) most frequently arising from the intestine (60%). For treatment of gastric
      MALT lymphoma, a combined approach (surgery followed by chemotherapy,
      antihelicobacter therapy followed by chemotherapy) was favoured (22 cases). Five
      year and 10-year overall survivals were 52% and 45% respectively. Knowledge of
      the Revised European American Lymphoma classification and the Helicobacter
      pylori/MALT association has influenced treatment approaches over the 10-year
      study period. For small intestinal lymphoma, surgery (with or without
      chemotherapy) gave 5- and 10-year survivals of 60%. Overall survival of patients
      with primary gastrointestinal lymphoma managed by the SLG is similar to that
      reported from other large series.

PMID- 11251168
TI  - Photodynamic therapy with hypericin in a mouse P388 tumor model: vascular effects
      determine the efficacy.
AB  - Hypericin, a polycyclic quinone obtained from plants of the Hypericum genus,
      exhibits strong photodynamic antitumor effects. In the present study, PDT
      efficacy of hypericin under different conditions was compared in a P388 mouse
      tumor model. Plasma and tumor drug measurements and assessment of vascular damage
      by fluorescein dye exclusion were performed to determine the relative
      contributions of vascular effects and direct tumor cytotoxicity. Furthermore, the
      influence of modifying tumor oxygenation on PDT effect was also evaluated. Study
      of PDT efficacy and tissue distribution revealed that PDT efficacy was more
      dependent on plasma concentration than tumor drug level. Fluorescein dye
      exclusion indicated the complete microvascular occlusion in the tumor and
      surrounding skin immediately after effective PDT treatments, while only a limited
      vascular occulation was observed after non-effective PDT treatment. It was found
      that neither tumor hypoxia induced by hydralazine nor increasing tumor
      oxygenation achieved by nicotinamide could significantly affect the effectiveness
      of various PDT protocols. These results suggest that tumor vasculature damage
      might be the primary mechanism of hypericin-mediated PDT effect. The existence of
      this potent secondary vascular effect is likely to account for the inability of
      tumor oxygenation modifiers to affect tumor response after PDT with hypericin.

PMID- 11251170
TI  - Ectopic expression of MyD118/Gadd45/CR6 (Gadd45beta/alpha/gamma) sensitizes
      neoplastic cells to genotoxic stress-induced apoptosis.
AB  - The MyD118/Gadd45/CR6 gene family (also termed Gadd45beta/alpha/gamma) has been
      identified as genes which are rapidly induced by genotoxic agents, during
      terminal differentiation, as well as by apoptotic cytokines. In recent years,
      evidence has emerged that the proteins encoded by these genes play pivotal roles
      in negative growth control, including growth suppression and apoptotic cell
      death. However, under what physiological condition these proteins mediate either
      cell cycle arrest or apoptosis, and the molecular nature of apoptotic pathways
      involved are currently unclear. Thus, to further explore the effects of these
      genes on cell growth and cell viability, either in the presence or absence of
      extrinsic stress, we have established M1 myeloblastic leukemia and H1299 lung
      carcinoma cell lines, where high level ectopic expression of MyD118, Gadd45, or
      CR6 can be induced by isopropyl beta-D-thiogalactopyranoside (IPTG). By taking
      advantage of these cell lines, it was observed that in the absence of genotoxic
      stress, inducible expression of MyD118, Gadd45 and/or CR6 resulted in retardation
      of cellular proliferation and accumulation of cells in the G1 phase of the cell
      cycle. Ectopic expression of these proteins also was found to sensitize the cells
      to apoptosis induced by genotoxic agents such as UV, MMS, gamma-irradiation and
      VP16. Finally, evidence has been obtained that in the absence of stress, ectopic
      expression of MyD118/Gadd45/CR6 is insufficient to activate the MTKl/JNK/p38
      stress cascade, and that enhancement of genotoxic stress induced apoptosis by
      these proteins may involve apoptotic pathways other than the JNK/p38 pathways.

PMID- 11251171
TI  - HPV16-E6 enhances mitoxantrone sensitivity in a human ovarian cancer line: an
      isolated instance or a trend?
AB  - A cellular isogenic system, in which wt-p53 expression level is challenged
      through human papilloma virus 16-E6 gene transfection, was previously developed
      in our laboratory. As an average trend, cancer lines bearing an inactivated p53
      have a general tendency toward an increased resistance to chemotherapeutic
      agents. However, using the above isogenic system, the transfected line (A2780-N9)
      was found to be more sensitive to taxol than the parental one (A2780-WT). In a
      NCI meta-analysis study the average trend is that altered p53 status is related
      to cellular resistance to topoisomerase II inhibitors, while it is irrelevant in
      determining sensitivity/resistance to mitotic spindle poisons. We report that our
      E6 transfected line, previously shown to be hypersensitive to taxol, is also
      clearly hypersensitive to a topoisomerase II inhibitor (mitoxantrone).
      Differences in cytotoxicity are more evident after a shorter/more intense
      exposure, than after a milder/longer exposure, being A2780-WT 27-fold more
      resistant than the transfected clone in the former case. These differences seem
      to be related to the different activities ("cross-talks") of E6 protein, among
      which shortening of p53 half-life is only one aspect. After mitoxantrone
      treatment A2780-N9 cells display also an increased propensity to apoptosis. In
      addition, a literature survey of E6 effects in transfected cancer cell lines,
      seems to suggest that chemosensitization to different classes of antineoplastic
      agents is the rule rather than the exception in these E6-based isogenic systems.

PMID- 11251172
TI  - The anti-malarial artesunate is also active against cancer.
AB  - Artesunate (ART) is a semi-synthetic derivative of artemisinin, the active
      principle of the Chinese herb Artemisia annua. ART reveals remarkable activity
      against otherwise multidrug-resistant Plasmodium falciparum and P. vivax malaria.
      ART has now been analyzed for its anti-cancer activity against 55 cell lines of
      the Developmental Therapeutics Program of the National Cancer Institute, USA. ART
      was most active against leukemia and colon cancer cell lines (mean GI50 values:
      1.11+/-0.56 microM and 2.13+/-0.74 microM , respectively). Non-small cell lung
      cancer cell lines showed the highest mean GI50 value (25.62+/-14.95 microM)
      indicating the lowest sensitivity towards ART in this test panel. Intermediate
      GI50 values were obtained for melanomas, breast, ovarian, prostate, CNS, and
      renal cancer cell lines. Importantly, a comparison of ART's cytotoxicity with
      those of other standard cytostatic drugs showed that ART was active in molar
      ranges comparable to those of established anti-tumor drugs. Furthermore, we
      tested CEM leukemia sub-lines resistant to either doxorubicin, vincristine,
      methotrexate, or hydroxyurea which do not belong to the N.C.I. screening panel.
      None of these drug-resistant cell lines showed cross resistance to ART. To gain
      insight into the molecular mechanisms of ART's cytotoxicity, we used a panel of
      isogenic Saccaromyces cerevisiae strains with defined genetic mutations in DNA
      repair, DNA checkpoint and cell proliferation genes. A yeast strain with a
      defective mitosis regulating BUB3 gene showed increased ART sensitivity and
      another strain with a defective proliferation-regulating CLN2 gene showed
      increased ART resistance over the wild-type strain, wt644. None of the other DNA
      repair or DNA check-point deficient isogenic strains were different from the wild
      type. These results and the known low toxicity of ART are clues that ART may be a
      promising novel candidate for cancer chemotherapy.

PMID- 11251173
TI  - Allelic imbalance and microsatellite instability in BRCA1 associated breast and
      ovarian tumors.
AB  - We have investigated the involvement of microsatellite instability (MSI) and
      allelic imbalance (AI) at chromosome 13q and 17 in 41 breast and 41 ovarian
      carcinomas and their association with BRCA1 and BRCA2 gene mutations. MSI was
      detected in 20% of ovarian and 7% of breast tumors. AI at the BRCA1 locus was
      detected in 59% and 32% of ovarian and breast tumors, respectively. At the BRCA2
      locus, AI rates were 49% and 44% for ovarian and breast tumors, respectively.
      Germline BRCA1 mutations, identified in 5 (12%) ovarian tumors and in one (2%)
      breast tumor were not associated with MSI. In only 2/5 BRCA1 positive tumors loss
      of the wild-type allele was observed. We conclude that BRCA1 mutation status is
      not associated with MSI and that MSI found in a fraction of ovarian tumors may
      reflect possible mutations in one of the DNA mismatch repair genes.

PMID- 11251174
TI  - Analysis of the p53 gene in parotid gland cancers: a relatively high frequency of
      mutations in low-grade mucoepidermoid carcinomas.
AB  - Mutations and overexpression of the p53 gene and protein were analyzed in 40
      cases with various types of parotid gland cancers. Mutations were found in 12
      cases (30%), and low-grade mucoepidermoid carcinomas (43%) and highly malignant
      carcinomas including adenocarcinoma, salivary duct carcinoma, and
      undifferentiated carcinoma (56%) showed a relatively high frequency of mutations.
      Overexpression of the protein was observed in 11 cases (28%) and 4 of the 11
      cases also had p53 mutations. These results suggest that mutations of the p53
      gene have significance in certain types of parotid cancers irrespective of the
      aggressiveness of a tumor type.

PMID- 11251175
TI  - Galectin-3 maintains the transformed phenotype of thyroid papillary carcinoma
      cells.
AB  - Galectin-3, a beta-galactoside-binding protein, is highly expressed in thyroid
      papillary carcinomas, while functional relevance of galectin-3 overexpression to
      the malignant phenotype remains elusive. In the present study we transfected
      galectin-3 antisense cDNA into the human thyroid papillary carcinoma cell line
      NPA which expresses an innately high level of galectin-3, and examined the effect
      of antisense inhibition of galectin-3 expression on the transformed phenotype.
      There was no difference in anchorage-dependent growth between the antisense
      clones and either the control or parental clones. In contrast, anchorage
      independent growth and saturation density of the antisense clones were
      significantly suppressed compared to those of either the control or parental
      clones. These results demonstrate that overexpression of galectin-3 in thyroid
      papillary carcinoma cells is necessary for the maintenance of transformed
      phenotype, and suggest galectin-3 as a potential target for therapeutic
      interventions in the future.

PMID- 11251176
TI  - Prognostic impact of cathepsin D and c-erbB-2 oncoprotein in a subgroup of node
      negative breast cancer patients with low histological grade tumors.
AB  - Some node-negative breast cancer patients, with initially good prognosis, relapse
      from their cancer and are poorly identified. In the present study, based on
      prospective data of 197 tumors, we measured cathepsin D (cath D, n=197), pS2
      protein (n=125), c-erbB-2 oncoprotein (n=100) and epidermal growth factor
      receptor (EGF-R, n=99) to better define the risk of relapse of node-negative
      patients in comparison with that defined by the clinical and histological
      factors. The median follow-up in surviving patients was 75 months. Univariate
      analysis indicated that patients with histological grade III tumors (the Scarff,
      Bloom and Richardson classification) had a much poorer prognosis than those with
      histological grade I or II tumors (P=0.0027 for relapse-free survival and
      P=0.0156 for overall survival). When the population of node-negative patients was
      divided by tertiles, high cath D levels showed a significant association with an
      early relapse (P=0.0316). Using cut-off values, patients with high cath D (> or
      =25 pmol/mg protein) or c-erbB-2 oncoprotein (> or =4 Human Neu Unit/microg
      protein) levels, had a significant worse relapse-free survival (P=0.0147 and
      0.0417, respectively). No prognostic information was supported by pS2 protein or
      EGF-R measurements. In multivariate analysis, histological grade, cath D and c
      erbB-2 oncoprotein remained independent predictors of recurrence (P=0.005, 0.0361
      and 0.0321, respectively). By combining low levels of cath D and c-erbB-2
      oncoprotein in histological grade I or II tumors, we identified a subgroup of
      patients with a 100% relapse-free survival probability at 6 years of follow-up.
      Moreover, the subgroup of patients with histological grade I or II tumors and
      high values of both cath D and c-erbB-2 oncoprotein showed a prognosis as poor as
      the subgroup defined by histological grade III alone, respectively 66% and 70%
      relapse-free survival at 6 years of follow-up. In conclusion, the combination of
      conventional prognostic factor (histological grade) and biochemical factors (cath
      D and c-erbB-2 oncoprotein) enabled us to identify, in this preliminary study, a
      subgroup of patients having an increased risk of relapse in a group (node
      negative patients with low histological grade tumors) considered as good
      prognosis.

PMID- 11251177
TI  - Amelioration of retrovirus-mediated gene transfer into hepatocellular carcinoma
      cells.
AB  - Recombinant retroviruses are by far the most frequently used vehicle in clinical
      gene therapy. No serious side-effects have been reported so far in clinical gene
      therapy trials using recombinant retroviral systems. Low titers of recombinant
      retroviruses, however, have limited the usefulness of recombinant retroviruses.
      To improve the efficiency of retrovirus-mediated gene transfer, we previously
      introduced the polyomavirus early region into amphotropic PA317 cells and
      established a modified retroviral packaging cell line, PAMP51. We demonstrate
      here that recombinant retroviruses produced by PAMP51-derived retroviral
      producing cells have approximately 10-fold higher titers compared with those
      produced by conventional PA317-derived retroviral producing cells. Importantly,
      recombinant retroviruses produced by PAMP-derived retroviral producing cells
      could infect hepatocellular carcinoma cells much more efficiently and could
      induce much stronger expression of a lacZ reporter gene in HCC cells compared
      with those produced by PA317-derived ones. These results indicate that
      recombinant retroviruses prepared from PAMP51-derived retroviral producing cells
      are much more useful than those prepared from PA317-derived ones and that the use
      of PAMP51 retroviral packaging cells may open up new avenues for the treatment of
      various types of cancer including hepatocellular carcinoma.

PMID- 11251178
TI  - Significance of integrin alpha2/beta1 in peritoneal dissemination of a human
      gastric cancer xenograft model.
AB  - In the present study, the role of integrin alpha2/beta1 in peritoneal
      dissemination of gastric cancer was investigated using an in vivo xenograft model
      for the highly metastatic MKN-45-P gastric cancer cells. Metastatic ability of
      MKN-45-P cells was significantly associated with the simultaneous expression of
      integrin alpha2 and alpha3 subunits. In an in vitro adhesion assay, neutralizing
      antibody for integrin alpha2 or beta1 subunit inhibited the adhesion of MKN-45-P
      cells to collagen type I and type IV. Moreover, the injection of anti-beta1
      monoclonal antibody reduced the number of cancer cells on the peritoneum in nude
      mice that had been inoculated with MKN-45-P cells. These results suggest that
      integrin alpha2/beta1 represents a candidate target molecule available for the
      prevention of gastric cancer peritoneal dissemination.

PMID- 11251179
TI  - Genetic alterations and expression of the protein phosphatase 1 genes in human
      cancers.
AB  - Recent studies have revealed that genetic alterations of the protein phosphatase
      genes, including PTEN, PPP2R1A, PPP2R1B and PPP1R3, are involved in human
      carcinogenesis. In the present study, we examined the genetic and expression
      status of nine protein phosphatase 1 (PP1) genes in 55 human cancer cell lines,
      consisting of 10 small cell lung cancers, 22 non-small cell lung cancers, 11
      colorectal cancers, 7 gastric cancers and 5 ovarian cancers. The PP1 genes
      examined were three catalytic subunit genes, PPP1CA, PPP1CB and PPP1CC, and six
      regulatory subunit genes, PPP1R1A, PPP1R2, PPP1R5, PPP1R6, PPP1R7 and PPP1R8.
      Three catalytic subunit genes and three regulatory subunit genes, PPP1R2, PPP1R7
      and PPP1R8, were ubiquitously expressed in the 55 cell lines, while PPP1R1A,
      PPP1R5, and PPP1R6 were differentially expressed. Possible missense mutations of
      the PPP1R5, PPP1R7 and PPP1R8 genes were detected in one (2%), two (4%) and one
      (2%) cell line, respectively. A rare, non-synonymous polymorphism was also
      identified in the PPP1R5 gene. Four of the 55 cell lines carried genetic
      alterations of several protein phosphatase genes, including PTEN, PPP1R3, PPP1R7
      and PPP1R8. Ubiquitous expression as well as a lack of genetic diversity of
      catalytic subunit genes suggested the essential role of these genes for the
      growth of cancer cells. In contrast, differential expression, somatic mutations
      and/or genetic polymorphisms of several regulatory subunit genes indicate the
      involvement of these genes in multistep carcinogenesis.

PMID- 11251180
TI  - Combinatory anti-tumor effects of electroporation-mediated chemotherapy and wild
      type p53 gene transfer to human esophageal cancer cells.
AB  - Delivery of electric pulses to an established solid tumor augments the
      permeability of cell membrane and increases the susceptibility of tumors to an
      anti-cancer agent that is administered in the vicinity of tumors. Forced
      expression of the wild-type p53 gene in tumor cells that have non-functional p53
      gene(s) can also enhance their sensitivity to a DNA-damaging agent. To
      investigate the feasibility of electroporation-mediated therapy for cancer,
      electric pulses were delivered to human esophageal tumors developed in nude mice
      after they received an anti-cancer agent and/or plasmid DNA containing the wild
      type p53 gene. The growth of esophageal tumors was suppressed with
      electroporation-mediated chemotherapy compared with the treatment with an anti
      cancer agent or electroporation alone. Intratumoral injection of the wild-type
      p53 gene into p53-mutated esophageal tumors followed by electroporation also
      inhibited tumor growth. When mice were administered with the wild-type p53 gene
      and an anti-cancer agent, subsequent electroporation produced a synergistic
      therapeutic effect. Combinatory transfer of plasmid DNA and a pharmacological
      agent by electroporation is thereby a possible therapeutic strategy for the
      treatment of solid tumors.

PMID- 11251181
TI  - BRCA1 and BRCA2 mutations among Finnish ovarian carcinoma families.
AB  - Germ-line mutations in BRCA1 and BRCA2 predispose to hereditary breast-ovarian
      cancer syndrome. In Finland, 21 different BRCA1/2 mutations have been identified
      and 14 of the mutations are founders that account for the great majority of all
      BRCA1/2 mutations. Our aim was to determine the prevalence of the 21 BRCA1/2
      mutations in Finnish ovarian carcinoma families. Mutations were screened in 23
      families with at least two cases of invasive epithelial ovarian carcinoma in the
      first-degree relatives. The families had been identified from a population-based
      series of 559 Finnish epithelial ovarian carcinoma patients. Fourteen of the
      families were site-specific ovarian carcinoma families, while breast cancer was
      present in nine families. Mutations were detected in five families: two had a
      mutation in BRCA1 and three in BRCA2. In one family, a novel, apparently disease
      causing missense mutation in the BRCA2 gene had been identified previously. Thus,
      26% of the Finnish ovarian carcinoma families were found to be BRCA1/2 mutation
      positive. Strong ovarian cancer family history and early-onset breast cancer were
      strongly associated with BRCA1/2 mutation status; all families with three ovarian
      carcinoma cases or early-onset breast cancer (<50 years) were mutation-positive,
      whereas all families with later-onset breast cancer as well as the majority
      (9/11) of the site-specific ovarian carcinoma families with minor ovarian cancer
      history (i.e. two affected cases) remained mutation-negative.

PMID- 11251182
TI  - Active roles of caspase-3 in human gastric carcinoma cell death by apoptosis
      inducing nucleosides from CD57+HLA-DRbright natural suppressor cell line.
AB  - The six apoptosis inducing nucleosides (AINs), which were isolated by high
      performance liquid chromatography from CD57+HLA-DRbright natural suppressor
      (57.DR-NS) cell cultures, induced apoptosis in human gastric carcinoma (GCIY)
      cells demonstrating the accumulation of sub-G1 DNA content and morphological
      changes. By means of DNA unwinding assay, it has been revealed that DNA strand
      breaks were initially involved in the apoptotic cell death of GCIY cells treated
      with AINs followed by activation of caspase cascades, especially caspase-3.
      Actually, the cleavage of fluorogenic substrate for caspase-3 was identified in
      the reaction. Whereas, the addition of caspase-3 inhibitor into the reaction
      prevented the cleavage of fluorogenic substrate for caspase-3 and resulted in the
      blockage of the sub-G1 DNA accumulation and DNA fragmentation as apoptotic
      signals. Thus, it was definitely elucidated that the activation of caspase-3
      displayed a key feature during AIN-induced apoptosis in GCIY cells.

PMID- 11251183
TI  - The interaction between beta-catenin, GSK3beta and APC after motogen induced cell
      cell dissociation, and their involvement in signal transduction pathways in
      prostate cancer.
AB  - The effect of HGF/SF was examined on the interactions between APC, GSK3beta and
      beta-catenin in prostate cancer cells LNCapFGC (E-cadherin positive) and PC-3 (E
      cadherin negative). Using immunoprecipitation, APC was found to be co
      precipitated with either GSK3beta or beta-catenin in both cell lines. Stimulation
      with HGF/SF showed no change in the co-precipitation status of these protein
      molecules. In contrast, co-precipitation between GSK3beta and beta-catenin was
      only observed in LNCapFGC cells, and increased upon continued exposure to the
      motogen HGF/SF. Furthermore, using immunofluorescence, stimulation with HGF/SF
      was found to increase the level of co-localised cytoplasmic staining between beta
      catenin and GSK3beta, in prostate cancer cells. RT-PCR revealed that there were
      no mutations within the binding regions between beta-catenin and GSK3beta. It is
      concluded, that uncomplexed cytoplasmic pools of beta-catenin associate more
      readily with the Axin complex in the absence of E-cadherin. Whereas, in the
      presence of E-cadherin, beta-catenin is stabilised by forming tight cell-cell
      contacts which may influence the invasive potential of cancer cells.

PMID- 11251184
TI  - Chlorophyllin protects cells from the cytostatic and cytotoxic effects of
      quinacrine mustard but not of nitrogen mustard.
AB  - Chlorophyllin (CHL), the sodium and copper salt of chlorophyll, is capable of
      inhibiting the mutagenic activity of many chemical compounds. Several mechanisms
      have been advanced to explain the antimutagenic activity of CHL, including its
      antioxidant properties and its ability to form complexes with mutagens. The
      present study was designed to reveal whether the heterocyclic aromatic nature of
      a potential mutagen is essential to its sensitivity to CHL. Toward this end, the
      inhibitory effect of CHL on two compounds of similar chemical reactivity
      (mustards), that either embodied an aromatic structure (quinacrine mustard; QM)
      or did not (nitrogen mustard; NM), were compared. Human leukemic HL-60 and breast
      carcinoma MCF-7 cells were treated with QM or NM in the absence or presence of
      various concentrations of CHL. Both QM and NM when administered for 1-2 h at
      micromolar concentrations exerted similar effects; both arrested cells in G2
      phase of the cell cycle, induced apoptosis and reduced the clonogenicity of MCF-7
      cells. The simultaneous addition of 0.22 M CHL to cultures receiving QM virtually
      abolished the QM-induced inhibition of cell growth and clonogenicity. In
      contrast, CHL had no effect on reducing the cytostatic or cytotoxic activity of
      NM. CHL alone, at a concentration of 0.22 M, had minimal effect on growth of HL
      60 cells slightly perturbing their progression through G2. The results are
      consistent with the model that explains the inhibition of the activity of
      mutagens or antitumor drugs with aromatic structures by CHL as mediated by its
      ability to sequester these molecules within heterologous mutagen:CHL complexes
      that are maintained by stacking interactions. Therefore, excess of chlorophyll in
      the diet, by sequestering aromatic mutagens (or antitumor drugs with a
      heterocyclic structure, if taken orally), may inhibit their accessibility to
      cells, thereby reducing their activity.

PMID- 11251185
TI  - RPR-115135, a new non peptidomimetic farnesyltransferase inhibitor, induces G0/G1
      arrest only in serum starved cells.
AB  - A new non peptidomimetic farnesyltransferase inhibitor, RPR-115135, was studied
      in an isogenic cell model system consisting of human colon cancer HCT-116 line.
      HCT-116 cells were transfected with an empty control pCMV vector or with a
      dominant-negative mutated p53 transgene to disrupt p53 function. Growth
      inhibitory effects of RPR-115135 were evaluated on cells growing under different
      conditions (serum starvation, serum starvation and recovery, nocodazole
      treatment). The cytotoxic activity of RPR-115135 was independent of the cell
      cycle status of the target cells. Addition of RPR-115135 only to cells exposed to
      reduced serum conditions (0.1% FCS) resulted in an enhanced ability of HCT-116
      cells to arrest in the G0/G1 phase. This arrest response appeared independent of
      p53/p21cip1/waf-1 function. A reduction of Cyclin A protein amount by RPR-115135
      was observed in both clones. These latter results suggest that RPR-115135 might
      down-regulate the cell cycle factor that would normally impede G0/G1 arrest.

PMID- 11251186
TI  - Physical interaction between p53 and primary response gene Egr-1.
AB  - The tumor suppressor p53 and primary response gene Egr-1 are nuclear
      transcription factors with regulatory roles in signal transduction pathways
      mediating cellular proliferation and growth arrest as well as the complex genetic
      programs controlling differentiation and programmed cell death. We identified a
      physical association between these regulatory proteins in vitro and in vivo.
      Recombinant p53 and Egr-1 fusion proteins complexed with in vitro translates of
      Egr-1 or p53, respectively, or with these respective proteins in cell lysates.
      This protein-protein interaction was detected in vivo by immunoprecipitation and
      Western blot analysis of serum-activated cellular lysates with high levels of
      induced Egr-1 and of human lung cancer cell lines with constitutive
      overexpression of Egr-1 and mutant p53. A p53 mutant at codon 154 did not bind
      Egr-1, while p53 proteins with point mutations at residues 156, 246, 247, and 273
      associated with this zinc finger transcription factor. p53 bound full-length Egr
      1 and an Egr-1 mutant with a deletion of the 5' transactivation region but did
      not associate with Egr-1 protein lacking an internal segment that included the
      first two zinc finger domains, suggesting that binding may require the presence
      of intact zinc finger motifs. A variant-sized Egr-1 protein expressed by lung
      fibroblast cell line MRC-9 was also bound by p53. The interaction of these
      regulatory proteins may alter multiple features of their biological activity
      especially with regard to the specificity of transcriptional control.

PMID- 11251187
TI  - Overexpression of platelet-derived growth factor B and downregulation of PDGF
      receptor alpha in human immortalized fibroblasts.
AB  - Since immortalization of cells is critical in multistep carcinogenesis, efforts
      should be made to elucidate the mechanisms of the immortalization. To determine
      whether platelet-derived growth factor (PDGF) signal pathways play a role in
      immortalization of cells, we compared mRNA expressions of PDGFs and their
      receptors in three immortalized human fibroblast cell lines (SUSM-1, OUMS-24F,
      and KMST-6) with their normal parent cells. As a result, mRNA expression of PDGF
      B (oncogene: c-sis) was upregulated in these immortalized cells. Unexpectedly,
      the expression of alpha- and beta-PDGF receptor genes was downregulated. PDGFR
      alpha mRNA was remarkably decreased. When exogenous PDGFR-alpha was expressed
      transiently in the KMST-6 cells, the morphology of the cells resembled that of
      normal cells. These results suggest that the overexpression of PDGF-B (c-sis) and
      downregulation of PDGFR-alpha are related to the phenotypic characteristics of
      immortalized human cells.

PMID- 11251188
TI  - Decreased tissue plasminogen activator and increased plasminogen activator
      inhibitors and increased activator protein-1 and specific promoter 1 are
      associated with inhibition of invasion in human A375 melanoma deprived of
      tyrosine and phenylalanine.
AB  - We previously found that dietary tyrosine (Tyr) and phenylalanine (Phe)
      restriction significantly decreased the metastatic phenotype of the pigmented
      murine B16BL6 melanoma in vivo and decreased the in vitro invasion of these
      cells. Here we report that invasion and chemoinvasion through GFR Matrigel of the
      human amelanotic A375 melanoma also is significantly inhibited by Tyr and Phe
      deprivation in vitro. Deprivation of these two amino acids decreased the
      secretion and protein expression of tissue-type plasminogen activator (tPA) while
      expression and secretion of plasminogen activator inhibitor (PAI-1 and PAI-2)
      were increased. Moreover, nuclear extracts of Tyr- and Phe-deprived cells
      exhibited increased binding of the transcription factors, activator protein-1 (AP
      1) and specific promoter-1 (Sp1), to consensus oligonucleotides as determined by
      electrophoretic mobility shift assay. Nuclear binding activity to the
      oligonucleotide consensus sequence for AP-1 was inhibited by antibody against c
      Fos and more effectively inhibited by an antibody against c-Jun. We conclude that
      decreased invasion and chemoinvasion of A375 melanoma cells deprived of Tyr and
      Phe are related to decreased secretion of tPA and increased secretion of PAIs.
      Increased AP-1 and Sp1 binding implicates these transcription factors in the
      regulation of PAI expression.

PMID- 11251189
TI  - Mating-activated brainstem catecholaminergic neurons in the female rat.
AB  - Central catecholaminergic systems play an important role in the control of
      reproductive activities including sexual behavior, luteinizing hormone (LH) and
      prolactin secretion. It has been reported that catecholaminergic neurons in the
      locus coeruleus (A6) are activated by mating in rabbits and ferrets, animals
      known as reflex ovulators. This study used Fos as a marker of neuronal activity
      to examine whether brainstem catecholaminergic neurons are activated by mating in
      the spontaneous ovulator, the female rat. Proestrous rats receiving intromissions
      (mated group) from males or mounts-without-intromission (mounted group) were
      sacrificed along with rats taken directly from their home cage (control group) 90
      min after the beginning of mating or mounting. Double-label immunocytochemistry
      was used to examine the expression of c-Fos in catecholaminergic neurons labeled
      by tyrosine hydroxylase (TH) antibody, or adrenergic neurons labeled by
      phenylethanolamine-N-methyl transferase (PNMT) antibody. Double label
      immunofluorescent immunohistochemistry was used to determine the number of
      neurons containing the estrogen receptor (ERalpha) that were activated by mating
      in these brain areas. The results showed that mating-with-intromissions induced a
      significant increase in the percentage of TH/Fos colabeled neurons in both A1 and
      A2 cells compared to mounting-without-intromission or control. In both these
      areas, over 50% ERalpha-ir neurons were activated after mating while mounting
      without-intromission did not affect the percentage of colabeled Fos/ERalpha
      neurons. In A6 region, neither the expression of Fos nor the percentage of TH/Fos
      colabeled cells was influenced by either mating or mounting compared to controls.
      The percentage of PNMT-containing neurons colabeled with Fos was not different in
      C1 and C2 among the three experimental groups. The results indicate that
      catecholaminergic neurons were activated by mating in A1 and A2 but not in
      adjoining adrenergic C1 and C2 cells. In contrast to the findings that
      catecholaminergic neurons in A6 are activated by mating in induced ovulators,
      mating did not affect neuronal activity in A6 neurons in the female rat. In A1
      and A2 areas, a high percentage of neurons containing ERalpha were activated by
      mating suggesting both tactile and hormonal information may converge on these
      populations of neurons. The activated catecholaminergic neurons in A1 and A2 may
      be an important pathway by which sensory information generated during sexual
      interaction modulates both behavior and pituitary function.

PMID- 11251190
TI  - Blunted brain metabolic response to ketamine in mice lacking D(1A) dopamine
      receptors.
AB  - The interaction of glutamatergic and dopamine neurotransmission is thought to
      have relevance to both the pathophysiology and pharmacotherapy of schizophrenia.
      For example, subanesthetic doses of the N-methyl-D-aspartate receptor (NMDA-R)
      antagonist ketamine induce schizophrenia-like behavioral effects in humans and
      both behavioral and brain metabolic activation in rodents. Blockade of NMDA-R
      results in dopamine release, and antipsychotic drugs that block dopamine
      neurotransmission decrease NMDA-R antagonist-induced behavioral activation. The
      involvement of dopamine receptors in brain metabolic activation induced by
      ketamine is, however, unknown. The present study used D(1A) knockout mice to
      determine the role of dopamine D(1A) receptors in the effects of subanesthetic
      doses of ketamine on both behavioral responses and on alterations in regional
      [14C]2-deoxyglucose (2-DG) uptake. There was less ketamine-induced behavioral
      activation in D(1A) knockout mice than in wild-type mice. In wild-type mice,
      ketamine (30 mg/kg) induced dramatic increases in 2-DG uptake in limbic cortical
      regions, hippocampal formation, nucleus accumbens, basolateral amygdala, and
      caudal parts of the substantia nigra pars reticulata. D(1A) knockout mice
      exhibited blunted metabolic activation in response to ketamine in a
      neuroanatomically specific manner. The selective D(1) antagonist, SCH23390 (0.3
      mg/kg), inhibited both ketamine-induced brain metabolic activation and behavioral
      responses in the wild-type mice, with a similar neuroanatomical specificity
      observed in the D(1A) knockout mice. Thus, the neuroanatomically selective role
      that D(1A) receptors play in ketamine-induced behavior and regional brain
      metabolic activation in mice provides a useful model for further studies of how
      the D(1A) receptor function may be altered in schizophrenia.

PMID- 11251191
TI  - Nitric-oxide-induced inhibition of glyceraldehyde-3-phosphate dehydrogenase may
      mediate reduced endothelial cell monolayer integrity in an in vitro model blood
      brain barrier.
AB  - The process of nitric-oxide (NO)-induced cellular toxicity may involve energy
      deprivation since the radical is reported to prevent both mitochondrial oxidative
      phosphorylation and glycolysis. In order to determine whether these processes are
      important in NO-induced blood-brain barrier (BBB) dysfunction, we used a cell
      culture model of the BBB and compared the effects of gaseous NO, potassium
      cyanide (KCN, a mitochondrial respiratory chain inhibitor) and iodoacetate [IA,
      an inhibitor of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH)] on endothelial cell ATP content, GAPDH activity and barrier integrity.
      NO lead to a rapid breakdown in model barrier integrity and resulted in a
      reduction in endothelial cell ATP content and GAPDH activity. KCN had no effect
      on endothelial cell ATP content or barrier integrity, while IA, at a
      concentration that completely blocked endothelial cell GAPDH activity, resulted
      in a rapid decline in ATP content but did not lead to a decline in barrier
      integrity until at least 2 h of exposure. These results indicate that inhibition
      of endothelial cell GAPDH activity rather than mitochondrial respiration causes
      an energy deficiency and delayed barrier dysfunction. However, the rapid
      detrimental effects of gaseous NO on barrier integrity cannot be fully explained
      by endothelial cell energy depletion and may be related to the actions of the
      free radical and its products on cellular lipids.

PMID- 11251193
TI  - Jun, Fos and Krox in the hippocampus after noxious stimulation: simultaneous
      input-dependent expression and nuclear speckling.
AB  - Stimulation of sensory C-fibres produces extensive expression of the Fos, Jun and
      Krox families of inducible transcription factors (ITFs) in many nociceptive CNS
      areas [28]. In the hippocampus, however, c-Fos is only weakly induced by such
      stimulation, and expression of the other ITFs has not been studied. Here we
      examine the effects of single, repeated and simultaneous C-fibre inputs on ITF
      expressions in the rat hippocampus. A brief, strong electrical stimulation of
      sciatic nerve C-fibres induced little or no expression of c-Fos or Krox-20. In
      contrast, FosB was induced and continued to rise in all areas, whereas the basal
      expressions of c-Jun and Krox-24 were initially reduced but then returned during
      the subsequent 36 h. A weak noxious cutaneous stimulus applied to one hindpaw
      induced only weak expressions of the ITFs. However, if the sciatic stimulation
      was applied contralaterally and 6 h beforehand, this weak stimulus strongly
      induced Krox-24, but not other ITFs, i.e. there was a potentiation of Krox-24
      expression. When these two stimuli were applied simultaneously a few c-Fos
      labelled cells did appear, and there was and an increased Krox-24 expression.
      There was also a strong potentiation of FosB and a strong reduction in c-Jun
      expression. This simultaneous stimulation was the only type of stimulation to
      induce expression of Krox-20. Also after simultaneous stimulation the majority of
      the nuclear labelling for FosB, but not of the other ITFs, had a speckled
      appearance. MK-801 blocked these changes in ITF expressions, but it could also
      cause the C-fibre stimulations to induce c-Fos and c-Jun in specific areas of the
      hippocampus. Thus C-fibre stimulation does affect transcription factor activity
      in the hippocampus; and the strong responses of some ITFs to simultaneous inputs
      points to their having a role as 'genetic coincidence detectors' in the
      hippocampus.

PMID- 11251192
TI  - Interaction of gacyclidine enantiomers with 'non-NMDA' binding sites in the rat
      central nervous system.
AB  - Gacyclidine, a channel blocker of N-methyl-D-aspartate receptors (NMDAR),
      exhibits potent neuroprotective properties and a low self-neurotoxicity.
      Preventing its interaction with NMDARs we demonstrate, through the use of its
      enantiomers, that gacyclidine also interacts with other ('non-NMDA') binding
      sites. The autoradiographic study showed that these sites displayed a uniform
      specific binding in the forebrain and a more discrete distribution in the
      molecular layer of the cerebellum. The 'non-NMDA' binding sites could exert a
      modulatory control on glutamatergic neurotransmission.

PMID- 11251194
TI  - Decreased epileptic susceptibility correlates with neuropeptide Y overexpression
      in a model of tolerance to excitotoxicity.
AB  - Prior epileptic episodes have been shown to decrease markedly the neuronal damage
      induced by a second epileptic episode, similar to the tolerance following an
      episode of mild ischemia. Endogenous neuroprotective effects mediated by various
      mechanisms have been put forward. This study investigated whether neuroprotection
      against the excitotoxic damage induced by re-exposure to an epileptic challenge
      can reflect a change in epileptic susceptibility. Tolerance was elicited in rats
      by a preconditioning session using intrahippocampal kainic acid (KA)
      administration followed at 1, 7 and 15-day intervals by a subsequent
      intraventricular KA injection. The degree of pyramidal cell loss in the
      vulnerable CA3 subfield contralateral to the KA-injected hippocampus was
      extensively reduced in animals experiencing KA ventricular administration. This
      neuroprotection was highly significant 1 and 7 days after injection, but not 15
      days after injection. In preconditioned animals, the after-discharge threshold
      was assessed as an index of epileptic susceptibility. It increased significantly
      from 1 to 15 days after intrahippocampal KA administration. Finally, an
      enhancement of neuropeptide Y expression in both non-principal cells and mossy
      fibers was detected, occurring at the same time as the decrease in epileptic
      susceptibility. These results provide further evidence of an 'epileptic
      tolerance' as shown by the substantial neuroprotective effect of a prior episode
      of epileptic activity upon subsequent epileptic insult and suggest that the
      prevention of excitotoxic damage after preconditioning results from an endogenous
      neuroprotective mechanism against hyperexcitability and seizures.

PMID- 11251195
TI  - Tetanic stimulation and metabotropic glutamate receptor agonists modify synaptic
      responses and protein kinase activity in rat auditory cortex.
AB  - We investigated whether tetanic-stimulation and activation of metabotropic
      glutamate receptors (mGluRs) can modify field-synaptic-potentials and protein
      kinase activity in rat auditory cortex, specifically protein kinase A (PKA) and
      protein kinase C (PKC). Tetanic stimulation (50 Hz, 1 s) increases PKA and PKC
      activity only if the CNQX-sensitive field-EPSP (f-EPSP) is also potentiated. If
      the f-EPSP is unchanged, then PKA and PKC activity remains unchanged. Tetanic
      stimulation decreases a bicuculline-sensitive field-IPSP (f-IPSP), and this
      occurs whether the f-EPSP is potentiated or not. Potentiation of the f-EPSP is
      blocked by antagonists of mGluRs (MCPG) and PKC (calphostin-C, tamoxifen),
      suggesting that the potentiation of the f-EPSP is dependent on mGluRs and PKC.
      PKC antagonists block the rise in PKC and PKA activity, which suggests that these
      may be coupled. In contrast, ACPD (agonist at mGluRs) decreases both the f-EPSP
      and the f-IPSP, but increases PKC and PKA activity. Quisqualate (group I mGluR
      agonist), decreases the f-IPSP, and increases PKA activity, suggesting that the
      increase in PKA activity is a result of activation of group I mGluRs.
      Additionally, the increase in PKC and PKA activity appears to be independent of
      the decrease of the f-EPSP and f-IPSP, because PKC antagonists block the increase
      in PKC and PKA activity levels but do not block ACPD's effect on the f-EPSP or f
      IPSP. These data suggest that group I mGluRs are involved in potentiating the f
      EPSP by a PKC and possibly PKA dependent mechanism which is separate from the
      mechanism that decreases the f-EPSP and f-IPSP.

PMID- 11251196
TI  - Hypothalamic projections to cardiovascular centers of the medulla.
AB  - The purpose of this project was to identify hypothalamic neurons having
      projections to two cardiovascular centers of the medulla, the rostral
      ventrolateral medulla (RVLM; a vasopressor region) and the nucleus of the
      solitary tract (NTS; a vasodepressor region). To accomplish this, fluorescent
      tracers (fast blue and diamidino yellow) were injected into NTS and RVLM, after
      each site had been physiologically identified in rats. In each case, one of the
      tracers was injected into the RVLM and another was injected into the NTS.
      Labelled neurons were subsequently observed along the entire rostral-caudal
      extent of the hypothalamus, where they were found in nuclei having known
      cardiovascular functions. Although the two groups of hypothalamomedullary neurons
      were largely overlapped in their distributions, less than 0.1% of the neurons
      were double labelled. In addition to this overlapping distribution of neurons,
      there were some areas within the hypothalamus where the two groups of
      hypothalamomedullary neurons were somewhat segregated. This clustering pattern
      was observed in the posterolateral hypothalamus (PLH) and, to a much lesser
      degree, in the paraventricular nucleus (PVN). Within the PLH, lying medial to the
      subthalamic nucleus, virtually all the labelled neurons projected exclusively to
      the NTS. Within the PVN, neurons projecting to the NTS were more numerous
      ventrally, whereas neurons projecting to the RVLM were more evenly dispersed
      within the PVN. In addition to hypothalamic labeling, clusters of labelled
      neurons were also observed in the zona incerta and the interstitial nucleus of
      the stria terminalis. Within the zona incerta, almost all the labelled neurons
      projected to the RVLM. Within the interstitial nucleus of the stria terminalis,
      neurons projecting to NTS were much more abundant in the dorsal portion of this
      nucleus; whereas, neurons projecting to the RVLM were more abundant ventrally.
      The findings of this study provide additional support to the notion that
      hypothalamic influences upon cardiovascular functions are in part mediated
      through hypothalamomedullary projections.

PMID- 11251197
TI  - Interleukin-2 modulates N-methyl-D-aspartate receptors of native mesolimbic
      neurons.
AB  - Interleukin (IL)-2 is a brain-derived cytokine that influences mesocorticolimbic
      dopamine release, and is associated with pathological outcomes that are mediated,
      at least in part, by aberrations in mesolimbic neurotransmission. The mechanisms
      by which IL-2 modulates mesolimbic transmission, however, are not known. The NMDA
      receptor/channel (NMDAR) plays an essential role in neuronal excitability of
      mesolimbic neurons; we thus examined in neonatal rats the effects of IL-2 on NMDA
      activated current (I(NMDA)) in voltage-clamped neurons freshly isolated from the
      ventral tegmental area (VTA), the site of origin of the mesolimbic system. IL-2
      (0.01-500 ng/ml) alone had no effect on membrane conductance. When co-applied
      with NMDA, IL-2 (50-500 ng/ml) significantly potentiated I(NMDA). In contrast,
      doses as low as 0.01 ng/ml markedly decreased the NMDA response. Dose-response
      analysis showed that IL-2 ( > 50 ng/ml) increased the maximal I(NMDA), without
      changing the EC(50), indicating that IL-2 potentiates I(NMDA) by increasing the
      efficacy of the NMDAR. Moreover, current-voltage analysis revealed that IL-2
      potentiation of I(NMDA) was voltage-dependent, being greater at negative
      potentials. In contrast, IL-2 inhibition of I(NMDA) was voltage-independent, and
      IL-2 did not alter the reversal potential. Additionally, IL-2 (1 ng/ml) shifted
      the NMDA concentration-response curve to the right, significantly increasing the
      EC(50) for NMDA without changing the maximal I(NMDA), suggesting that IL-2
      inhibits the NMDAR by a competitive mechanism. IL-2 thus acts as a potent
      modulator of the NMDAR. IL-2-induced alterations of responses to NMDAR activation
      may contribute to synaptic plasticity in the mesolimbic system and to
      pathological outcomes associated with this system.

PMID- 11251198
TI  - Activation of skeletal muscle afferents evokes release of glutamate in the
      subretrofacial nucleus (SRF) of cats.
AB  - The subretrofacial nucleus (SRF) is a region of the rostral ventrolateral medulla
      known to play a crucial role in sympathoexcitation. SRF neurons send direct
      projections to the intermediolateral cell columns of the spinal cord where they
      form synaptic contact with preganglionic sympathetic motor neurons. Activation of
      this neural pathway increases sympathetic outflow to the heart and blood vessels
      affecting cardiac function and vasomotor tone. Previous studies utilizing
      electrophysiological recording techniques and c-Fos expression have established
      that the activity of SRF neurons is increased during skeletal muscle contraction.
      However, the excitatory neurotransmitter mediating this increased activity
      remains in question. In the present study, static contraction of the triceps
      surae was induced by electrical stimulation of L7 and S1 ventral roots in
      anesthetized cats (n=12). Endogenous release of glutamate (Glu) from the SRF was
      recovered by microdialysis and measured by HPLC. Static muscle contraction for 4
      min increased mean arterial pressure (MAP) 38+/-4 mmHg from a control level of
      102+/-12 mmHg (P< 0.05). During muscle contraction the extracellular
      concentration of Glu recovered from the SRF increased from 623+/-117 to 1078+/
      187 nM (P<0.05). To determine the effect of muscle contraction on Glu release in
      the absence of synaptic input from other reflexogenic areas, contraction was
      repeated following acute sinoaortic denervation and vagotomy. Following this
      denervation, muscle contraction increased MAP 41+/- 4 mmHg (P < 0.05) and Glu
      concentration from 635+/-246 to 1106+/-389 nM (P < 0.05). Muscle paralysis
      prevented the increases in MAP and Glu concentration during ventral root
      stimulation. These results suggest that: (i) Glu is released in the SRF during
      activation of contraction-sensitive skeletal muscle afferent fibers in the cat;
      and (ii) synaptic input from other reflexogenic areas appears to be ineffective
      in modulating the release of Glu in the SRF during static muscle contraction.

PMID- 11251199
TI  - Differential expression of thymosins beta(4) and beta(10) during rat cerebellum
      postnatal development.
AB  - The beta-thymosins are a family of actin monomer-sequestering proteins widely
      distributed among vertebrate classes. The most abundant beta-thymosins in
      mammalian species are thymosin beta(4) (Tbeta(4)) and thymosin beta(10)
      (Tbeta(10)), two small peptides (43 amino acids) sharing a high degree of
      sequence homology. In the present work, we have analyzed the distribution of
      Tbeta(4) and Tbeta(10) in the developing and adult rat cerebellum using in situ
      hybridization and immunohistochemistry techniques. Our results show that the
      temporal and cellular patterns of expression of both beta-thymosins are
      different. In the young (7 and 18 postnatal days) and adult (1 and 4 months old)
      rat cerebellum, Tbeta(4) was mainly expressed in the glia (microglia, Golgi
      epithelial cells and oligodendrocytes), neurons (granule cells and Purkinje
      cells), and in the capillaries. In 14-month-old rats, the Tbeta(4)
      immunoreactivity was only detected in some microglia cells. In young and adult
      animals, most of the Tbeta(10) immunoreactivity was localized in several types of
      neuronal cells including granule cells, Golgi neurons and Purkinje cells. In old
      animals, a faint Tbeta(10) signal could be detected in a few Purkinje cells. Our
      results suggest that each beta-thymosin could play a different function in the
      control of actin dynamics.

PMID- 11251200
TI  - Effect of central and peripheral administration of a nitric oxide synthase
      inhibitor on morphine hyperthermia in rats.
AB  - The effect of central and peripheral administration of a nitric oxide synthase
      inhibitor, N-nitro-L-arginine methyl ester (L-NAME), on morphine hyperthermia was
      studied in male Sprague-Dawley rats. The first series of experiments examined the
      effect of subcutaneous (s.c.) administration of L-NAME on the hyperthermia
      induced by morphine given s.c. in doses of 4 and 15 mg/kg. L-NAME, at a s.c. dose
      of 50 mg/kg, per se, had no influence on body temperature (T(b)).
      Coadministration of L-NAME (50 mg/kg, s.c.) with the higher dose of morphine (15
      mg/kg, s.c.) caused a significant suppression of morphine hyperthermia during the
      first 30 min and then produced hypothermia. In contrast, s.c. injection of L-NAME
      (50 mg/kg, s.c.) failed to alter the hyperthermic response induced by the lower
      dose of morphine (4 mg/kg). In the second series of experiments, we investigated
      the effect of intracerebroventricular (i.c.v.) administration of L-NAME on the
      hyperthermia induced by morphine given s.c. L-NAME, itself, given i.c.v. at a
      dose of 1 mg did not evoke any change in T(b). Intracerebroventricular
      administration of L-NAME (1 mg) blocked the hyperthermia induced by 15 mg/kg
      morphine during the first 30 min and induced a slight hypothermia but did not
      alter the hyperthermia induced by 4 mg/kg morphine. The results indicate that
      either central or peripheral NO synthesis is required for the production of
      hyperthermia induced by 15 mg/kg of morphine. However, NO synthesis does not seem
      to be involved in the hyperthermic process induced by 4 mg/kg of morphine.

PMID- 11251201
TI  - Anatomical sparing in the superior colliculus of hemispherectomized monkeys.
AB  - Using the monkey as a model for human hemispherectomy, the effects of early
      removal of a whole cerebral hemisphere on the cytoarchitecture and cytochrome
      oxidase histochemistry of the superior colliculus (SC) were evaluated. Results
      show that the SC ipsilateral to the cortical lesion suffers a 29.9% average
      volume reduction and a 32.7% total loss of neurons compared to the contralateral
      SC. Neuronal densities and metabolic activity are similar in normal and
      hemispherectomized monkeys. Furthermore, the ipsi- and contralesional SC receive
      retinal inputs as revealed with intraocular injections of tritiated proline.
      These data suggest that the superior colliculus retains functional capabilities
      following hemispherectomy in monkey.

PMID- 11251202
TI  - Female gastrin-releasing peptide receptor (GRP-R)-deficient mice exhibit altered
      social preference for male conspecifics: implications for GRP/GRP-R modulation of
      GABAergic function.
AB  - We studied female GRP-R-deficient mice with respect to olfactory function and
      social behavior toward male conspecifics. Results of a food exploration test
      (hidden cookie method) revealed that the olfactory ability of these mutant mice
      is identical to that of wild-type mice. However, when preference toward either a
      socially dominant or subordinate male mouse was assessed in a social preference
      test, wild-type mice showed a greater preference for socially dominant males than
      did GRP-R-deficient mice. In contrast, in a social investigation test to an
      anesthetized male mouse, GRP-R-deficient mice exhibited greater investigatory
      behavior toward the target male than did wild-type mice. When female C57BL/6J
      mice were given diazepam (0, 1, 2 or 4 mg/kg, i.p.), their investigatory behavior
      to the anesthetized male target was increased in a dose-dependent manner.
      Conversely, i.p. administration of bicuculline (1 mg/kg) significantly decreased
      the social investigatory behavior of female GRP-R-deficient mice, but not of wild
      type mice. These results indicate that female GRP-R-deficient mice exhibit
      altered responsiveness to male conspecifics relative to their wild-type
      counterparts, and suggest that this outcome may be attributable, at least in
      part, to altered GABAergic function in these mutant mice.

PMID- 11251203
TI  - Medial versus lateral parabrachial nucleus lesions in the rat: effects on
      cholecystokinin- and D-fenfluramine-induced anorexia.
AB  - The two major components of the pontine parabrachial nucleus (PBN), the medial
      (gustatory) and lateral (visceral) subdivisions, have been implicated in a
      variety of ingestive behaviors. The present study examined the influence of
      bilateral ibotenic acid lesions of the medial or lateral PBN on the anorectic
      effects of two systemically administered drug treatments. In Experiment 1, 24-h
      food-deprived rats where injected with sulfated cholecystokinin (26-33) (CCK; 0,
      4.0, or 8.0 microg/kg) and then given 60 min access to food. In Experiment 2, the
      influence of D-fenfluramine (DFEN; 0, 0.5, 1.0, or 2.0 mg/kg) on deprivation
      induced feeding was examined in the same rats using the same behavioral procedure
      as in Experiment 1. Lesions of the lateral PBN abolished CCK-, but not DFEN
      induced anorexia whereas lesions of the medial PBN augmented DFEN-, but had no
      influence on CCK-induced anorexia. The results suggest that the satiating effects
      of CCK and DFEN are mediated through different mechanisms involving,
      respectively, visceral and orosensory processing.

PMID- 11251204
TI  - Mild postischemic hypothermia is neuroprotective in the immature rat neocortex
      slice.
AB  - Mild hypothermia as an intervention after perinatal asphyxia may prevent
      neurological damage in the newborn. We used stimulus-induced field potentials to
      monitor recovery from oxygen and glucose deprivation (OGD) in neocortex slices of
      6-8-day-old wistar rats. OGD after a latency of 10.7+/-2.1 min (mean+/-S.E.)
      resulted in an anoxic depolarisation with an amplitude of 5.4+/-2.4 mV. Mild
      hypothermia of 31 degrees C (vs. 35 degrees C in the control group) was applied
      for 60 min after end of OGD. The 20, 40, 60 and 80% recovery of the field
      potential amplitude was significantly faster in the hypothermia group in
      comparison to the control group. These data indicate that mild postischemic
      hypothermia may have neuroprotective effects after perinatal asphyxia.

PMID- 11251205
TI  - Photic regulation of circadian rhythms and the expression of p75 neurotrophin
      receptor immunoreactivity in the suprachiasmatic nucleus in rats.
AB  - Neurotrophic factors have been implicated in the mechanism underlying photic
      regulation of circadian rhythms in mammals. In rats, the most abundant
      neurotrophin receptor found in the suprachiasmatic nucleus (SCN), the circadian
      clock, is the low affinity p75 neurotrophin receptor (p75NTR). This receptor is
      expressed by retinal afferents of the SCN, but nothing is known about its role in
      photic regulation of circadian rhythms. We show here that neonatal treatment with
      the retinal neurotoxin, monosodium glutamate (MSG), which has no effect on photic
      entrainment of circadian rhythms, nearly completely abolished p75NTR
      immunoreactivity in the SCN in rats. These findings suggest that p75NTR from
      retinal sources do not play an essential role in the mechanism mediating photic
      entrainment of circadian rhythms in rats.

PMID- 11251206
TI  - Modafinil does not affect serotonin efflux from rat frontal cortex synaptosomes:
      comparison with known serotonergic drugs.
AB  - Modafinil did not affect spontaneous and K(+)-evoked [3H]5-HT efflux from
      cortical synaptosomes while it increased K(+)-evoked tritium efflux from cortical
      slices, an action that became stronger in the presence of paroxetine. In
      contrast, DL-fenfluramine and fluoxetine were able to enhance spontaneous and/or
      K(+)-evoked tritium efflux from synaptosomes and slices. These results suggest
      that modafinil does not affect 5-HT transmission from cortical synaptosomes and
      that its 5-HT releasing action is different from that of DL-fenfluramine and
      fluoxetine.

PMID- 11251207
TI  - Region specific increase of dopamine receptor D1/D2 mRNA expression in the brain
      of mu-opioid receptor knockout mice.
AB  - Previous pharmacological studies have indicated the possible existence of
      functional interactions between opioidergic and dopaminergic neurons in the CNS.
      In this study, the expression of mRNAs encoding dopamine receptor D1/D2 was
      examined to investigate whether there is a change in the dopamine pathway of mice
      lacking the mu-opioid receptor by in situ hybridization technique. In the mu
      opioid receptor knockout mice, the expression of dopamine receptor D1 mRNA was
      increased in the olfactory tubercle, nucleus accumbens, caudate putamen, and the
      layer VI of the neocortex compared with that of wild-type mice. The expression of
      dopamine receptor D2 mRNA was also increased in the olfactory tubercle, caudate
      putamen, and the nucleus accumbens of mu-opioid receptor knockout mice. These
      results indicate that there are compensational changes in the dopaminergic
      systems of mu-opioid receptor knockout mice.

PMID- 11251208
TI  - Inhibition of interleukin-1beta and prostaglandin E(2) thermogenesis by glycyl
      glutamine, a pro-opiomelanocortin-derived peptide.
AB  - Interleukin-1beta (IL-1beta) and other cytokines produce fever by stimulating
      prostaglandin E(2) (PGE(2)) synthesis in thermoregulatory regions of the preoptic
      area and anterior hypothalamus (POA/AH). Prostaglandin E(2) is thought to raise
      body temperature, at least in part, by stimulating beta-endorphin release from
      pro-opiomelanocortin neurons that innervate the POA/AH. In this study, we
      investigated whether glycyl-glutamine (beta-endorphin(30-31)), an inhibitory
      dipeptide synthesized from beta-endorphin post-translationally, inhibits IL-1beta
      and PGE(2)-induced hyperthermia. Hyperthermic sites were identified by
      microinjecting PGE(2) (3 fmol/1 microl) into the medial preoptic area (mPOA) of
      conscious, unrestrained rats. Interleukin-1beta (1 U) injection into the same
      PGE(2) responsive thermogenic sites in the mPOA elicited a prolonged rise in
      colonic temperature (T(c)) (+1.02+/-0.06 degrees C) that persisted for at least 2
      h. Glycyl-glutamine (3 nmol) co-injection into the mPOA inhibited IL-1beta
      thermogenesis completely (T(c)=-0.18+/-0.22 degrees C). Glycyl-glutamine had no
      effect on body temperature when given alone to normothermic rats. Co-injection of
      individual amino acids, glycine and glutamine (3 nmol each amino acid), failed to
      influence IL-1beta-induced thermogenesis, which indicates that Gly-Gln hydrolysis
      does not explain its inhibitory activity. Glycyl-glutamine (3 nmol) also
      prevented the rise in body temperature produced by PGE(2) (PGE(2)=0.89+/-0.05
      degrees C; PGE(2) plus Gly-Gln=-0.16+/-0.14 degrees C), consistent with evidence
      that PGE(2) mediates IL-1beta-induced fever. These findings demonstrate that Gly
      Gln inhibits the thermogenic response to endogenous pyrogens.

PMID- 11251209
TI  - Expression of the anaphylatoxin C5a receptor in the oligodendrocyte lineage.
AB  - Expression of the C5a receptor in the central nervous system has been
      demonstrated on microglia, astrocytes and neurons. In the present study, we
      demonstrate C5aR expression in vitro by rat and murine O2-A progenitor cells and
      oligodendrocytes. We also observed that in vitro differentiation of O2-A
      progenitors into mature oligodendrocytes is accompanied by down-regulation of
      C5aR mRNA expression. These results suggest that the C5aR may be a marker for
      oligodendroglial differentiation and play a role in oligodendrocyte function.

PMID- 11251210
TI  - Intrathecal cyclosporin prolongs survival of late-stage ALS mice.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized
      by upper and lower motor neuron death with ascending paralysis leading to death.
      In a transgenic mouse model of ALS (SOD1-G93A) weakness appears at 3 months of
      age, and because of progressive paralysis leads to death by 5 months. Cyclosporin
      A (CsA) is well known, for its extracerebral effect, as an immunosuppressant in
      organ transplantation. When able to access the brain, CsA is an effective
      neuroprotective agent mainly due to its protection of mitochondria through
      inhibition of the mitochondrial permeability transition. CsA does not cross the
      intact blood-brain barrier and was in the present study delivered to the brain
      through an infusion into the lateral cerebral ventricle. Injections started at
      the onset of late disease when weakness of the hindlimbs was apparent. CsA
      treatment prolonged the survival of ALS transgenic mice as compared to vehicle
      treated controls. This finding implicates mitochondrial function in ALS and may
      have significance for human disease.

PMID- 11251211
TI  - Cyclooxygenase-2 expression in the hippocampus of genetically epilepsy
      susceptible El mice was increased after seizure.
AB  - It has been suggested that cyclooxygenase (COX)-2 and prostaglandin play a role
      in epilepsy. We studied the expression of COX-2 in the hippocampus and the effect
      of oral administration of indomethacin, a COX inhibitor, on seizure activity in
      genetically seizure-susceptible El mice. COX-2 protein significantly increased in
      the hippocampi of El mice after epileptic seizure. Indomethacin did shorten the
      duration from seizure onset to full recovery in El mice although the threshold
      and the duration of seizure were not changed.

PMID- 11251212
TI  - Cadmium toxicity in synaptic neurotransmission in the brain.
AB  - Chronic exposure to cadmium causes central nervous system disorders, e.g.
      olfactory dysfunction. To clarify cadmium toxicity in synaptic neurotransmission
      in the brain, the movement of cadmium in the synapses was examined using in vivo
      microdialysis. One and 24 h after injection of (109)CdCl(2) into the amygdala of
      rats, (109)Cd release into the extracellular space was facilitated by stimulation
      with high K(+), suggesting that cadmium taken up by amygdalar neurons is released
      into the synaptic clefts in a calcium- and impulse-dependent manner. Moreover, to
      examine the action of cadmium in the synapses, the amygdala was perfused with
      artificial cerebrospinal fluid containing 10-30 microM CdCl(2). The release of
      excitatory neurotransmitters, i.e. glutamate and aspartate, into the
      extracellular space was decreased during perfusion with cadmium, while the
      release of inhibitory neurotransmitters, i.e. glycine and gamma-amino butyric
      acid (GABA), into the extracellular space was increased during the period. These
      results suggest that cadmium released from the amygdalar neuron terminals affect
      the degree and balance of excitation-inhibition in synaptic neurotransmission.

PMID- 11251213
TI  - Nicotine accelerates reversal of long-term potentiation and enhances long-term
      depression in the rat hippocampal CA1 region.
AB  - In the hippocampal CA1 region, low-frequency stimulation (LFS; 200 pulses at 1
      Hz) causes reversal of long-term potentiation (depotentiation, DP) and long-term
      depression (LTD), both of which are thought to be the cellular substrate of
      learning and memory. Because nicotine enhances learning and memory, we examined
      if nicotine modulates DP and LTD in the hippocampal CA1 region. Bath application
      of nicotine during LFS accelerated DP, that is, potentiated synaptic responses in
      hippocampal CA1 neurons returned to pre-tetanic control levels more rapidly in
      the presence of nicotine. Because a similar acceleration of DP was observed using
      the alpha7 nicotinic acetylcholine receptor (nAChR)-selective antagonist
      methyllcaconitine (MLA), the nicotine effect appeared to be at least partly
      mediated by nicotine-induced desensitization of alpha7 nAChRs. Delivery of LFS in
      the presence of nicotine or MLA also depressed synaptic responses in a naive
      pathway and facilitated LTD, that is, the magnitude of LTD was larger when the
      drug was present during LFS. Thus, these results demonstrate that nicotine
      facilitates DP and LTD, which may represent, at least in part, the cellular
      mechanism underlying nicotine-induced cognitive enhancement.

PMID- 11251214
TI  - Acute and chronic nicotine exposure reverse age-related declines in the induction
      of long-term potentiation in the rat hippocampus.
AB  - Long-term potentiation (LTP) is widely considered to be the cellular substrate of
      learning and memory. The induction of LTP becomes more difficult with age in
      parallel with declining learning and memory ability. Because nicotine improves
      learning and memory in aged rats, we examined the effects of acute and chronic
      nicotine exposure on age-related declines in LTP induction. We found that acute
      nicotine exposure lowered the threshold for LTP induction in the aging
      hippocampus. The effect of nicotine was mimicked by the alpha7 nicotinic
      acetylcholine receptor (nAChR) antagonist methyllycaconitine and blocked by the
      non-alpha7 nAChR antagonist dihydro-beta-erythroidine, suggesting that both
      nicotine-mediated desensitization of alpha7 nAChRs and activation of non-alpha7
      nAChRs contribute to the nicotine effect. The non-alpha7 nAChR agonist A85380
      that facilitates the induction of LTP in the young hippocampus had no effect,
      however, suggesting that at least one pathway involving non-alpha7 nAChRs was
      altered by aging. Chronic nicotine treatment of aged rats also lowered the
      threshold for LTP induction and acute nicotine exposure lowered the threshold
      further in the chronic-nicotine-treated aged hippocampus. These results not only
      suggest that the mechanisms mediated by acute and chronic nicotine exposure are
      different, but also demonstrate that age-associated declines in LTP induction can
      be reversed with nicotine treatment.

PMID- 11251216
TI  - Caspase-3-deficiency induces hyperplasia of supporting cells and degeneration of
      sensory cells resulting in the hearing loss.
AB  - Caspase-3 is one of the cystein proteases that play essential roles in programmed
      cell death. As such, brain development is profoundly affected by caspase-3
      deficiency, resulting in hyperplasia and abnormal cell organization (Kuida et
      al., Nature 1996;384:368-372). In the present study, we used caspase-3 (-/-) mice
      to show that caspase-3 deficiency results in severe hearing loss, hyperplasia of
      supporting cells and degeneration of sensory hair cells. The greater epithelial
      ridge, a remnant of the primordial organ of Corti, persists throughout all of the
      turns of cochlea in 2-week-old caspase-3 (-/-) mice, which indicates that the
      morphology of the cochlea is immature. The number of border cells, that develop
      from the greater epithelial ridge and are one of the supporting cells of the
      inner hair cell, increase significantly in both 2- and 5-week-old caspase-3 (-/-)
      mice. On the other hand, abnormal fused stereocilia can be seen in both 2- and 5
      week-old caspase-3 (-/-) mice, and disarrangement and loss of sensory hair cells
      are observed in 5-week-old caspase-3 (-/-) mice. Taken together, both hyperplasia
      and degeneration occur simultaneously in the inner ear of the caspase-3 (-/-)
      mice, suggesting that caspase-3-dependent apoptosis is necessary for the
      development and formation of a properly functioning auditory system in mammals.

PMID- 11251215
TI  - Dissociations between the effects of intra-accumbens administration of
      amphetamine and exposure to a novel environment on accumbens dopamine and
      cortical acetylcholine release.
AB  - Previous research has demonstrated an interaction between the effects of
      amphetamine and exposure to a novel environment on the activity of neurons in the
      nucleus accumbens. Given a model in which these accumbens efferents gate the
      excitability of basal forebrain cholinergic corticopetal neurons, the
      administration of intra-accumbens amphetamine was hypothesized to potentiate the
      increase in cortical acetylcholine produced by introduction to a novel
      environment. Dual probe microdialysis revealed no synergistic interactions
      between exposure to a novel environment and amphetamine on nucleus accumbens
      dopamine or cortical acetylcholine efflux. This finding indicates that exposure
      to a novel environment failed to recruit the telencephalic activation of the
      nucleus accumbens presumably necessary to reveal modulatory effects of accumbens
      dopaminergic transmission on cortical acetylcholine release.

PMID- 11251218
TI  - Applications of nylon membrane arrays to gene expression analysis.
AB  - Gene expression analyses by hybridization of probes derived from mRNA to cDNA
      targets arrayed on a nylon membranes have been performed with increasing
      frequency and success over the last decade. While the initial costs of generating
      arrays are moderately high, they are now available commercially as complete
      packages which include the membranes and associated image analysis software for
      acquisition and processing of the data. Arrays can be used to generate
      information concerning the expression of mRNA from cells treated with various
      agents or from different tissues, e.g. comparing diseased with normal controls.
      To date, many groups, including immunologists, have used this technology to
      examine gene expression within their area of biological interest. The main
      characteristic of these systems is the large amount of data generated, since the
      expression of many thousands of genes are measured in parallel. The main
      practical issues are sensitivity of detection, reproducibility, comparability
      with other systems (e.g. Northern blots) and processing of data. Some of the
      significant applications of nylon array technology to date are reviewed in this
      chapter, and with these issues in mind, we include a discussion of our own
      experiences in this area.

PMID- 11251219
TI  - Analysis of cellular adhesion by microarray expression profiling.
AB  - Microarrays of oligonucleotides or cDNAs can be used to establish the expression
      profiles of numerous genes in a single experiment. We have established a
      microarray platform to identify genes in a number of different pathological
      conditions, particularly those with an inflammation component. This platform
      utilised the output of an eosinophil sequencing project in which 1069 sequences
      were identified that were not represented in the public domain. An eosinophil
      model cell line, AML14.3D10, was used to investigate cell adhesion. The
      transcription profile of adhered and non-adhered AML 14.3D10 cells was shown to
      be both technically and biologically reproducible. A number of genes were found
      differentially expressed in the adhered vs. non-adhered populations. In the
      adhered population, the expression of these genes was restricted compared to
      brain, lung, kidney and especially bone marrow. However, the differentially
      regulated genes were not among those genes most restricted to eosinophils. We
      discuss the implications of transcription profiling on gene annotation and its
      potential utility for the identification of targets for drug intervention.

PMID- 11251220
TI  - Application of differential display to immunological research.
AB  - The majority of immunological processes are mediated by cell-to-cell contact or
      receptor-ligand interactions that transmit intracellular signals and affect the
      regulation of transcription in the nucleus. As a consequence, precursor cells
      develop into their respective lineages and cells differentiate further during an
      immune response. In order to study changes in normal cells or even cells that
      have been isolated from diseased tissue, a number of approaches have been
      developed. One such method, differential display (DDRT-PCR), is a versatile
      technique for the analysis of gene expression that is based on RT-PCR and
      denaturing polyacrylamide gel electrophoresis. This technique is applicable to
      multiple samples of clonal or purified cell populations as well as to complex
      tissues and can be used to provide mRNA fingerprints. However, the main purpose
      of DDRT-PCR is to isolate differentially regulated genes in biological systems.
      The method is carried out without prior hypothesis as to which genes should be
      examined and so increases the possibility of identifying completely novel and
      unexpected changes in transcription. A major drawback has been the isolation of
      false positive clones and the need to confirm the results of analysis by another
      method. This makes DDRT-PCR labour intensive. A number of strategies have been
      recommended to reduce these problems, including reverse-northern analysis as a
      confirmatory step for screening putative differentials. In order to reduce the
      number of gel fingerprints that would be required to cover all the mRNAs in a
      cell, several focused approaches have been suggested. These include targeted
      differential display for the isolation of multigene families that have conserved
      protein domains or gene signatures and subtractive differential display whereby
      one population is subtracted from the other prior to screening. The purpose of
      this review is to provide some guidance to the immunologist who might wish to
      apply DDRT-PCR in their research. A number of examples where DDRT-PCR has been
      used successfully in immunological research are included.

PMID- 11251222
TI  - Open systems: panoramic views of gene expression.
AB  - Since their development in the early 1990s, differential gene expression (DGE)
      technologies have been applied to a multitude of biological challenges, both for
      the purpose of basic biological research and as a valuable tool for the discovery
      and development of pharmaceuticals. In this review we survey a class of DGE
      technologies collectively referred to as 'open' architecture systems. These
      technologies are distinct from the 'closed' DGE technologies (quantitative PCR,
      chip technologies), in that no pre-existing biological or sequence information is
      necessary and they are applicable to any species. Examples of open systems
      include GeneCalling, SAGE, TOGA, READS, and their progenitor DGE technologies,
      differential display and cDNA representational difference analysis. We review
      these technologies and summarize a specific application using GeneCalling for
      novel gene discovery. Additionally, the significance of data management and
      experimental design in this new age of expression analysis is discussed.

PMID- 11251221
TI  - Use of serial analysis of gene expression (SAGE) technology.
AB  - Serial analysis of gene expression, or SAGE, is an experimental technique
      designed to gain a direct and quantitative measure of gene expression. The SAGE
      method is based on the isolation of unique sequence tags (9-10 bp in length) from
      individual mRNAs and concatenation of tags serially into long DNA molecules for a
      lump-sum sequencing. The SAGE method can be applied to the studies exploring
      virtually any kinds of biological phenomena in which the changes in cellular
      transcription are responsible. SAGE is a highly competent technology that can not
      only give a global gene expression profile of a particular type of cell or
      tissue, but also help us identify a set of specific genes to the cellular
      conditions by comparing the profiles constructed for a pair of cells that are
      kept at different conditions. In this review, we present an outline of the
      original method, several studies achieved by using the method as a major
      strategic tool, technological difficulties and intrinsic problems that emerged,
      and improvements and modifications of the method to cope with these drawbacks. We
      then present our modified SAGE procedure that generates longer sequence tags (14
      bp) rather in detail, and the profile (80K profile) derived from HeLa cells that
      is composed of 80000 tags obtained from a single library. In addition, a series
      of smaller profiles (2, 4, 10, 20 and 40K) was made by dividing the 80K profile.
      When we compared these smaller profiles with respect to tag counts for a number
      of genes, it became apparent that counts of most gene tags increase stably and
      constantly as the size of profiles increase, while several genes do not. This may
      be another problem we have to keep in mind, when the profiles are compared for
      the identification of 'specific genes'.

PMID- 11251223
TI  - Protein and antibody arrays and their medical applications.
AB  - Many new gene products are being discovered by large-scale genomics and
      proteomics strategies, the challenge is now to develop high throughput approaches
      to systematically analyse these proteins and to assign a biological function to
      them. Having access to these gene products as recombinantly expressed proteins,
      would allow them to be robotically arrayed to generate protein chips. Other
      applications include using these proteins for the generation of specific
      antibodies, which can also be arrayed to produce antibody chips. The availability
      of such protein and antibody arrays would facilitate the simultaneous analysis of
      thousands of interactions within a single experiment. This chapter will focus on
      current strategies used to generate protein and antibody arrays and their current
      applications in biological research, medicine and diagnostics. The shortcomings
      of these approaches, the developments required, as well as the potential
      applications of protein and antibody arrays will be discussed.

PMID- 11251224
TI  - Methods and approaches in the analysis of gene expression data.
AB  - The application of high-density DNA array technology to monitor gene
      transcription has been responsible for a real paradigm shift in biology. The
      majority of research groups now have the ability to measure the expression of a
      significant proportion of the human genome in a single experiment, resulting in
      an unprecedented volume of data being made available to the scientific community.
      As a consequence of this, the storage, analysis and interpretation of this
      information present a major challenge. In the field of immunology the analysis of
      gene expression profiles has opened new areas of investigation. The study of
      cellular responses has revealed that cells respond to an activation signal with
      waves of co-ordinated gene expression profiles and that the components of these
      responses are the key to understanding the specific mechanisms which lead to
      phenotypic differentiation. The discovery of 'cell type specific' gene expression
      signatures have also helped the interpretation of the mechanisms leading to
      disease progression. Here we review the principles behind the most commonly used
      data analysis methods and discuss the approaches that have been employed in
      immunological research.

PMID- 11251225
TI  - Cisplatin stops tubulin assembly into microtubules. A new insight into the
      mechanism of antitumor activity of platinum complexes.
AB  - Despite numerous studies considering DNA as a primary target of cisplatin attack,
      this work is the first to show the pure effect of cisplatin on the process of
      tubulin assembly/disassembly in vitro. When platinated, tubulin does not assemble
      into microtubules (direct electron microscopic studies). In place of them, highly
      stable and inert circled rings arise. Such tubulin aggregates are unable to
      participate in the process of chromosome separation during the mitosis, thus
      blocking cell division in living cells, which is a direct evidence of cisplatin
      antitumor activity. Cisplatin attack on tubulin causing blockage of tubulin
      assembly occurs via a two-step binding to GTP in the GTP center of tubulin
      ((195)Pt, (31)P NMR studies). The calculated binding rates are close to those
      reported in cisplatin-DNA interactions. The mechanism of cisplatin attack on
      tubulin is proposed.

PMID- 11251226
TI  - The A--B transition: temperature and base composition effects on hydration of
      DNA.
AB  - Natural DNAs and some polynucleotides organised in fiber present the A--B form
      transition at a relative humidity (r.h.) which depends on the temperature. A
      shift of the midpoint of that helix--helix transition to higher r.h. values is
      observed when the temperature is risen. It is shown that the average number of
      water molecules associated to a nucleotide pair is the relevant parameter for the
      A-B transition and that this parameter can be given a precise value by a
      combination of different r.h. and temperature values. The minimum number of water
      molecules necessary to get the B form depends on the base composition of the DNA.
      It is observed that AT base pairs have a higher affinity toward water molecules
      than GC base pairs. In the B form there are 27 water molecules per GC nucleotide
      pair and 44 per AT pair. Moreover, we noted that the fraction of nucleotides in
      the B form as a function of the average number of water molecules associated per
      base pair does not depend on the temperature. The A helical form is obtained with
      about 11 water molecules per nucleotide pair and this number is not very
      sensitive to the base composition of DNA.

PMID- 11251227
TI  - Surface modification of polyhydroxyalkanoate films and their interaction with
      human fibroblasts.
AB  - A poly(3-hydroxybutylate-co-hydroxyvalerate) (PHA) film containing 34 mol.% 3
      hydroxyvalerate (Biopol D600P) was prepared by the solvent cast method using a 10
      wt.% chloroform solution of PHA. The PHA film was exposed to an oxygen plasma
      glow discharge to produce peroxides on its surfaces. These peroxides were then
      used as catalysts for the polymerization of acrylic acid (AA) in order to prepare
      carboxyl group-introduced PHA (PHA-C). Insulin-immobilized PHA was prepared using
      the coupling reaction of PU-C with insulin. The surface-modified PHAs were then
      characterized by attenuated total reflection Fourier transform infrared
      spectroscopy, electron spectroscopy for chemical analysis, and a contact angle
      goniometer. The amounts of insulin directly coupled to the carboxyl groups on PHA
      C and coupled to the terminus amino groups of the grafted polyethylene oxide were
      2.9 and 0.8 microg cm(-2), respectively. The PHA water contact angle (75 degrees
      ) decreased with AA grafting (33 degrees ) and insulin immobilization (31 degrees
      ), thereby exhibiting the increased hydrophilicity of the modified PHAs. When
      compared with PHA and PHA-C, the proliferation of human fibroblasts in the
      presence of serum was significantly accelerated on the insulin-immobilized PHAs.

PMID- 11251228
TI  - A differential scanning calorimetric study of the effects of metal ions,
      substrate/product, substrate analogues and chaotropic anions on the thermal
      denaturation of yeast enolase 1.
AB  - The thermal denaturation of yeast enolase 1 was studied by differential scanning
      calorimetry (DSC) under conditions of subunit association/dissociation, enzymatic
      activity or substrate binding without turnover and substrate analogue binding.
      Subunit association stabilizes the enzyme, that is, the enzyme dissociates before
      denaturing. The conformational change produced by conformational metal ion
      binding increases thermal stability by reducing subunit dissociation. 'Substrate'
      or analogue binding additionally stabilizes the enzyme, irrespective of whether
      turnover is occurring, perhaps in part by the same mechanism. More strongly bound
      metal ions also stabilize the enzyme more, which we interpret as consistent with
      metal ion loss before denaturation, though possibly the denaturation pathway is
      different in the absence of metal ion. We suggest that some of the stabilization
      by 'substrate' and analogue binding is owing to the closure of moveable
      polypeptide loops about the active site, producing a more 'closed' and hence
      thermostable conformation.

PMID- 11251229
TI  - Isolation and characterization of the exopolysaccharide produced by Streptococcus
      thermophilus SFi20.
AB  - This paper reports isolation, structural characterization and some physico
      chemical properties in aqueous solution of the exopolysaccharide (EPS) produced
      by Streptococcus thermophilus strain SFi20. The yield of the purified EPS was
      found to be reproducible and close to the average value of 143 mg/l. The chemical
      structure, previously suggested, has been confirmed on the basis of NMR data.
      Viscometric, chiro-optical and rheological measurements have been carried out
      with the aim of characterizing the conformational state of the polysaccharide in
      aqueous solution. All the data reported indicate that the EPS does not undergo a
      cooperative conformational transition under the investigated experimental
      conditions. Furthermore, the viscosity data and the viscoelastic behaviour
      suggest that the polymer is rather flexible and adopts a random coil conformation
      in aqueous solution.

PMID- 11251230
TI  - Heteronuclear nuclear magnetic resonance assignments, structure and dynamics of
      SUMO-1, a human ubiquitin-like protein.
AB  - The structure of a ubiquitin-like protein, small ubiquitin-related modifier-1
      (SUMO-1), was earlier determined using homonuclear nuclear magnetic resonance
      (NMR) spectroscopy, since the spectral quality of the protein was not suitable
      for heteronuclear NMR data collection. In this study, a slightly different
      construct of the SUMO-1 gene was used for protein over-expression. The protein
      purified from this construct showed high spectral qualities, therefore, multi
      dimensional heteronuclear NMR data for a dynamic study and structural
      determination were acquired. The structure of SUMO-1 obtained in this study
      differs in several respects from the structure obtained from homonuclear NMR
      data. Furthermore, structural differences were observed between the new SUMO-1
      and ubiquitin structures. These differences may be important for SUMO-1-specific
      recognition in cells. Additionally, relaxation parameters indicate that SUMO-1
      undergoes highly anisotropic tumbling in solution and that the long amino (N)
      terminal sequence of SUMO-1 is highly dynamic with increasing flexibility towards
      the end.

PMID- 11251231
TI  - Effect of dissolved oxygen concentration in the fermentation medium on
      transformation of the carbon sources during the biosynthesis of poly(3
      hydroxybutyrate-co-3-hydroxypropionate) by Alcaligenes latus.
AB  - Effects of fermentation conditions on the comonomer composition and its
      distribution of poly(3-hydroxybutyrate-co-3-hydroxypropionate) [P(3HB-co-3HP)]
      have been investigated for bacterial synthesis of P(3HB-co-3HP)s by Alcaligenes
      latus from sucrose and 3-hydroxypropionate (3HPA) mixed carbon sources.
      Comparison of the microstructures of these samples drew a conclusion that when
      the concentration of oxygen dissolved (DO) in the fermentation medium was
      controlled between 5 and 20% (based on the concentration at saturation), the 3HP
      content and the comonomer compositional distribution (CCD) of the copolymer would
      not be influenced by the DO values. The concentration of the carbon sources was
      monitored during the fermentation. The results indicated that the comonomer
      composition and its distribution of P(3HB-co-3HP)s were interrelated to the
      amounts of carbon sources transported into the bacterial cells. When the bacteria
      consumed more sucrose, the more 3HPA they would utilize, and the broader the CCD
      of the copolymer would be. Furthermore, the efficiencies of the transformation of
      the two carbon sources to the copolymer constituents were found to be similar.

PMID- 11251232
TI  - The effect of temperature on the Donnan potentials in biological polyelectrolyte
      gels: cornea and striated muscle.
AB  - The effect of temperature on the fixed electric charge in biological
      polyelectrolyte gels was studied between 10 and 35 degrees C using the Donnan
      microelectrode technique. Two tissues; cornea and striated muscle were used. In
      cornea, there is a gentle and uniform decrease in fixed charge over the
      temperature range. In rigor muscle, there is a dramatic step-function decrease in
      charge at around 28 degrees C. There is a charge decrease in relaxed muscle at
      around the same temperature, but the step function is less distinct. The
      significance of these different experimental relationships is discussed in
      relation to the Saroff model for ion binding to proteins, linked to the possible
      disordering effects of excess electric charge. The diverse effects in these
      systems are important for the physiological functions of the different tissues.

PMID- 11251233
TI  - Prediction of the subcellular location of prokaryotic proteins based on the
      hydrophobicity index of amino acids.
AB  - An algorithm of predicting the subcellular location of prokaryotic proteins is
      proposed in this paper. In addition to the amino acid composition, the auto
      correlation functions based on the hydrophobicity profile of amino acids along
      the primary sequence of the query protein have been used. Consequently, the best
      predictive accuracy to date has been achieved. Of the 997 prokaryotic proteins in
      the database used here, 688 cytoplasmic, 107 extracellular and 202 periplasmic
      proteins, the overall predictive accuracies are as high as 97.7 and 90.4% in the
      resubstitution and jackknife tests, respectively, using the hydrophilicity value
      of Hopp and Woods. The underlying mechanism of the improvement is also discussed.
      This work would be useful for a systematic analysis of the great amounts of
      prokaryotic genome sequences. The computer programs used in this paper are
      available on request via email.

PMID- 11251234
TI  - Immunosenescence: a review.
AB  - Aging involves the morphological and functional integrity of all organs,
      including the cellular and humoral immunological functions. The main alterations
      can be listed as follows: (i) Thymic involution resulting in the decreased number
      of lymphoid precursor T- and B-cells. (ii) Reduced proliferative capacity of T
      cells; loss of lymphocyte subgroups as a consequence of the shortening of
      telomeres. (iii) Qualitative deficiency of B-lymphocytes with a reduced response
      to exogenous antigens. (iv) Compromised activity of the accessory cells, both
      directly by depressing the chemotactic and phagocytic responses, and indirectly
      by increasing the prostaglandin production which inhibit the proliferation of T
      cells. (v) Alterations in the production and secretion of various cytokines. (vi)
      Other factors like the general physiological conditions, the nutritional state,
      psychological habit and various hormone levels.

PMID- 11251235
TI  - Comorbidity and rehabilitation.
AB  - Screening patients admitted to a rehabilitation center has become important.
      Actually, co-existing diseases are not very often evaluated and their importance
      is underestimated. At our department 166 consecutive patients were enrolled. The
      Cumulative Illness Rating Scale (CIRS) appeared to be the most suitable for these
      cases. In this series, stroke patients presented with higher severity and higher
      comorbidity than the hip fracture patients. The hip fracture cases were older but
      the stroke cases had higher severity and comorbidity. Comorbidity, also, showed a
      significant negative correlation with FIM in the stroke patients. These data show
      that severe comorbid conditions influence the functional autonomy. Severity and
      comorbidity were correlated both in the hip fracture and stroke cases. A review
      of geriatric literature demonstrates lower values in patients in rehabilitation.
      The difference is due to our accurate selection of patients at admission, where
      general health conditions are considered. In conclusion, the CIRS should be used
      as a method for selecting patients at admission and as a prognostic index for
      improvement at discharge. The CIRS, however, has some inconveniences and
      amelioration is necessary, such as the inclusion of a double testing (admission
      discharge), psychiatric disturbances and a new item for skin alone. The Severity
      Index was higher in women, who were older than men, whereas, comorbidity was the
      same. In the patients suffering from hip fracture, the age was higher in women,
      but dependence, severity and comorbidity did not statistically differ between the
      groups.

PMID- 11251236
TI  - Insomnia and depressive symptoms in patients with Parkinson's disease.
      Relationship to health-related quality of life. An interview study of patients
      living at home.
AB  - The objectives of this study were to describe the prevalence of insomnia and
      depressive symptoms in patients with Parkinson's disease (PD) and to relate those
      symptoms to health-related quality of life. A total of 102 patients living at
      home, most of them moderately to severely disabled, were interviewed. Of them 43
      patients were women with a mean age of 70 (range 58-79). The mean age for the men
      was 71 (range 56-80). Time since diagnosis was <2 years for 57%, 2-10 years for
      31% and >10 years for 12%. The geriatric depression scale (GDS) and Livingston's
      insomnia scale were used. The results were related to quality of life as measured
      with the SF-36 health survey. The prevalence of insomnia was 80%. Moderate
      depressive symptoms were found in 47% and severe depressive symptoms in 5%.
      Patients with insomnia or with depressive symptoms had a significantly impaired
      quality of life on all eight scales of the SF-36. In a stepwise regression
      analysis the presence of pain and ache and depressive symptoms were significantly
      related to insomnia. The variables most related to depressive symptoms were Hoehn
      and Yahr group and insomnia. Hoehn and Yahr groups (more disability) were
      significantly related to insomnia and depressive symptoms. Thus, insomnia and
      depressive symptoms are prevalent in PD and influence quality of life and should,
      therefore, be considered when evaluating patients with PD.

PMID- 11251237
TI  - Neural network analysis in predicting 2-year survival in elderly people: a new
      statistical-mathematical approach.
AB  - We designed this study to test the usefulness of artificial neural networks (ANN)
      in assessing 2-year survival in elderly persons, and to understand the net's
      logical functioning, thus determining the relative importance of the single
      biological and clinical variables which influence survival. ANN are statistical
      mathematical tools able to determine the existence of a correlation between
      series of data and, once 'trained', to predict output data given input data.
      Although ANN have been applied in various areas of medical research, they have
      only very recently been applied in geriatrics (Cacciafesta et al., 2000. Arch.
      Gerontol. Geriatr. 31 (in press)). We built up an ANN to investigate how 17
      clinical variables relating to a sample of 159 elderly people affect survival,
      and the possibility of predicting 2-year survival or non-survival for each single
      subject. When tested on a sample of 20 elderly people, the trained network gave
      the correct answer in 85% of the cases. We then extracted the mathematical
      function that the net used for calculating the output (survival) for each set of
      input data (clinical variables). Using this formula, we investigated how some
      clinical variables influence 2-year survival: we found that a low serum
      cholesterol level is an unfavourable characteristic in relation to survival. We
      conclude-despite the fact that the sample studied was relatively small-that ANN
      are useful in predicting 2-year survival in elderly people. The mathematical
      function we obtained from the net seems useful in determining the relative
      importance of single variables related to survival.

PMID- 11251238
TI  - Prevalence of potential respiratory pathogens in the mouths of elderly patients
      and effects of professional oral care.
AB  - To evaluate the effectiveness of professional oral health care in reducing the
      risk of aspiration pneumonia, we examined the prevalence of potential respiratory
      pathogens in gargled samples from elderly persons. Samples were obtained from 54
      elderly subjects over 65 years of age who required daily nursing care, from 21
      healthy elderly subjects over 65 years old, and from 22 healthy young subjects
      under 30 as controls. The prevalence of possible pathogens was determined by
      culture and the polymerase chain reaction. The percentages detected in samples of
      Streptococcus pneumoniae, Staphylococcus species, methicillin-resistant
      Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans from elderly
      patients requiring daily nursing care were 63.0, 37.0, 14.8, 5.6 and 66.7,
      respectively. The numbers of C. albicans cells recovered in samples from elderly
      subjects were significantly higher than those recovered from the healthy young
      group (P<0.001). Elderly patients needing daily care and receiving professional
      oral health care had lower prevalences and cell numbers of C. albicans than did
      the elderly patients without such oral care. This study showed that professional
      oral health care in elderly requiring daily nursing care reduced the cell numbers
      of potential respiratory pathogens.

PMID- 11251239
TI  - Some problematic behaviors in Alzheimer's dementia.
AB  - We examined 18 patients with problematic behaviors in relation to their
      individual characteristics and their possible relationship to certain aspects of
      dementia namely cognitive impairment, stage of illness, language impediment and
      functional disability. They formed part of an earlier assessment of 94 patients
      with dementia-related problems. Ten had altered eating habits and eight (8.5%) of
      them had hyperphagia. One exhibited an incomplete form of Kluver-Bucy Syndrome.
      Two had pathological stealing and one scatolia (smearing of faeces). The
      remaining had bizzare behaviors such as screaming and head banging. The majority
      of the patients were in the moderate category in relation to the four domains
      tested. The study revealed that behavioral problems in the more severe dementia
      becomes less of a problem to the caregivers and others. These behaviors could
      dramatically affect the social and interpersonal relationships resulting in
      community, family and caregiver burden.

PMID- 11251240
TI  - Dementia-related behavioral changes - a physician's office-based study.
AB  - This is a physician's office-based retrospective study of 161 dementia patients
      with (94) and without (67) behavioral symptoms. Those with disturbed behavior
      were subdivided into patients with behavior changes at initial evaluation and
      those encountered in existing dementia. The two main groups and the subgroups
      were studied in relation to individual and disease characteristics. The targeted
      behaviors (aggression, psychosis, aberrant motor behavior and miscellaneous) were
      analyzed in relation to four dementia-related domains namely cognitive
      impairment, language impairment, stage of illness (CDR) and functional disability
      (Rankin grades). No differences were observed between the two main groups in
      relation to age and gender and to cognitive impairment, language impairment and
      disability except for stage of illness (P=0.01). There were no significant
      differences in terms of age and gender in the two subgroups and in the frequency
      of single targeted behaviors but for psychosis which was the most commonly
      recorded disturbed behavior. There was no correlation between the single targeted
      behaviors and the different domains examined but for aberrant motor behavior and
      stage of illness (P=0.04) in the subgroups.

PMID- 11251241
TI  - Panoparticulate systems for improved drug delivery.

PMID- 11251242
TI  - Nanosuspensions as particulate drug formulations in therapy. Rationale for
      development and what we can expect for the future.
AB  - An increasing number of newly developed drugs are poorly soluble; in many cases
      drugs are poorly soluble in both aqueous and organic media excluding the
      traditional approaches of overcoming such solubility factors and resulting in
      bioavailability problems. An alternative and promising approach is the production
      of drug nanoparticles (i.e. nanosuspensions) to overcome these problems. The
      major advantages of this technology are its general applicability to most drugs
      and its simplicity. In this article, the production of nanoparticles on a
      laboratory scale is presented, special features such as increased saturation
      solubility and dissolution velocity are discussed, and special applications are
      highlighted, for example, mucoadhesive nanosuspensions for oral delivery and
      surface-modified drug nanoparticles for site-specific delivery to the brain. The
      possibilities of large scale production -- the prerequisite for the introduction
      of a delivery system to the market -- are also discussed.

PMID- 11251243
TI  - Design of nanoparticles composed of graft copolymers for oral peptide delivery.
AB  - The development of a dosage form that improves the absorption of peptide and
      protein drugs via the gastrointestinal tract is one of the greatest challenges in
      the pharmaceutical field. Many researchers have taken up the challenge, using
      approaches including mucoadhesive drug delivery, colon delivery, particulate drug
      delivery such as nanoparticles, microcapsules, liposomes, emulsions, micelles,
      and so on. The objective of this article is to provide the reader with outlines
      of novel nanoparticle technologies for oral peptide delivery based on polymer
      chemistry. The physicochemical properties of nanoparticles and their behavior on
      exposure to physiological media are greatly dominated by their chemical
      structures and surface characteristics. We will especially focus on the design of
      nanoparticles composed of novel graft copolymers having a hydrophobic backbone
      and hydrophilic branches as drug carriers.

PMID- 11251244
TI  - Mucoadhesive nanoparticulate systems for peptide drug delivery.
AB  - This chapter describes the preparation of and methods for evaluating mucoadhesive
      nanoparticulate systems, including liposomes and polymeric nanoparticles.
      Mucoadhesive ability is conferred on the particulate systems by coating their
      surface with mucoadhesive polymers such as chitosan and Carbopol. The feasibility
      of this surface modification was confirmed by measuring the zeta potential.
      Several methods of evaluating the mucoadhesive properties of particulate systems
      have been reported in the literature. We have also developed some novel
      evaluation procedures including a particle counting method using a Coulter
      counter for polymer-coated liposomes. The mucoadhesive properties of the polymer
      coated liposomes and polymeric nanoparticles were confirmed by means of these
      mucoadhesion tests. In applying these mucoadhesive nanoparticles to the oral and
      pulmonary administration of peptide drugs, more effective and prolonged action
      was observed in comparison with non-coated systems, thereby confirming the
      usefulness of mucoadhesive nanoparticulate systems for the delivery of peptide
      drugs.

PMID- 11251245
TI  - Lymphatic targeting with nanoparticulate system.
AB  - Much effort has been made to achieve lymphatic targeting of drugs using colloidal
      carriers. This paper reviews the recent progress in the development of
      biodegradable nanoparticulate systems, including nanospheres, emulsions, and
      liposomes. The major purpose of lymphatic targeting is to provide an effective
      anticancer chemotherapy to prevent the metastasis of tumor cells by accumulating
      the drug in the regional lymph node via subcutaneous administration. The
      objectives of lymph targeting also involve the localization of diagnostic agents
      to the regional lymph node to visualize the lymphatic vessels before surgery, and
      the improvement of peroral bioavailability of macromolecular drugs, like
      polypeptides or proteins, which are known to be selectively taken up from the
      Peyer's patch in the intestine. Nanocapsules, which are ultrafine oily droplet
      coated polymeric substances, are probably one of the most promising candidates of
      colloidal carriers. Surface engineering by the interfacial deposition method can
      provide a suitable size distribution and necessary surface characteristics to the
      nanocapsules. Our recent in vivo study proved that polyisobutylcyanoacrylate
      nanocapsules showed enhanced accumulation of drug in the lymph node, compared
      with other carriers such as emulsions and liposomes.

PMID- 11251246
TI  - Nanoparticulate systems for brain delivery of drugs.
AB  - The blood--brain barrier (BBB) represents an insurmountable obstacle for a large
      number of drugs, including antibiotics, antineoplastic agents, and a variety of
      central nervous system (CNS)-active drugs, especially neuropeptides. One of the
      possibilities to overcome this barrier is a drug delivery to the brain using
      nanoparticles. Drugs that have successfully been transported into the brain using
      this carrier include the hexapeptide dalargin, the dipeptide kytorphin,
      loperamide, tubocurarine, the NMDA receptor antagonist MRZ 2/576, and
      doxorubicin. The nanoparticles may be especially helpful for the treatment of the
      disseminated and very aggressive brain tumors. Intravenously injected doxorubicin
      loaded polysorbate 80-coated nanoparticles were able to lead to a 40% cure in
      rats with intracranially transplanted glioblastomas 101/8. The mechanism of the
      nanoparticle-mediated transport of the drugs across the blood-brain barrier at
      present is not fully elucidated. The most likely mechanism is endocytosis by the
      endothelial cells lining the brain blood capillaries. Nanoparticle-mediated drug
      transport to the brain depends on the overcoating of the particles with
      polysorbates, especially polysorbate 80. Overcoating with these materials seems
      to lead to the adsorption of apolipoprotein E from blood plasma onto the
      nanoparticle surface. The particles then seem to mimic low density lipoprotein
      (LDL) particles and could interact with the LDL receptor leading to their uptake
      by the endothelial cells. After this the drug may be released in these cells and
      diffuse into the brain interior or the particles may be transcytosed. Other
      processes such as tight junction modulation or P-glycoprotein (Pgp) inhibition
      also may occur. Moreover, these mechanisms may run in parallel or may be
      cooperative thus enabling a drug delivery to the brain.

PMID- 11251247
TI  - Polysaccharide colloidal particles as delivery systems for macromolecules.
AB  - Mucosal delivery of complex molecules such as peptides, proteins,
      oligonucleotides, and plasmids is one of the most intensively studied subjects.
      The use of colloidal carriers made of hydrophilic polysaccharides, i.e. chitosan,
      has arisen as a promising alternative for improving the transport of such
      macromolecules across biological surfaces. This article reviews the approaches
      which have aimed to associate macromolecules to chitosan in the form of colloidal
      structures and analyzes the evidence of their efficacy in improving the transport
      of the associated molecule through mucosae and epithelia. Chitosan has been shown
      to form colloidal particles and entrap macromolecules through a number of
      mechanisms, including ionic crosslinking, desolvation, or ionic complexation,
      though some of these systems have been realized only in conjunction with DNA
      molecules. An alternative involving the chemical modification of chitosan has
      also been useful for the association of macromolecules to self-assemblies and
      vesicles. To date, the in vivo efficacy of these chitosan-based colloidal
      carriers has been reported for two different applications: while DNA-chitosan
      hybrid nanospheres were found to be acceptable transfection carriers, ionically
      crosslinked chitosan nanoparticles appeared to be efficient vehicles for the
      transport of peptides across the nasal mucosa. The potential applications and
      future prospects of these new systems for mucosal delivery of macromolecules are
      highlighted at the end of the chapter.

PMID- 11251248
TI  - Nanoparticulate systems for the delivery of antisense oligonucleotides.
AB  - Antisense oligonucleotides are molecules that are able to inhibit gene expression
      being therefore potentially active for the treatment of viral infections or
      cancer. However, because of their poor stability in biological medium and their
      weak intracellular penetration, colloidal drugs carriers such as nanoparticles
      were developed for the delivery of oligonucleotides (ODN). ODN associated to
      nanoparticles were shown to be protected against degradation and to penetrate
      more easily into different types of cells. As a consequence, nanoparticles were
      shown to improve the efficiency of ODNs for the inhibition of the proliferation
      of cells expressing the point mutated Ha-ras gene. In vivo,
      polyalkylcyanoacrylate (PACA) nanoparticles were able to efficiently distribute
      the ODNs to the liver whereas the alginate nanosponges could concentrate the ODNs
      in the lungs. Finally, ODN loaded to PACA nanoparticles were able to improve in
      mice, the treatment of RAS cells expressing the point mutated Ha-ras gene.

PMID- 11251249
TI  - Block copolymer micelles for drug delivery: design, characterization and
      biological significance.
AB  - Recently, colloidal carrier systems have been receiving much attention in the
      field of drug targeting because of their high loading capacity for drugs as well
      as their unique disposition characteristics in the body. This paper highlights
      the utility of polymeric micelles formed through the multimolecular assembly of
      block copolymers as novel core-shell typed colloidal carriers for drug and gene
      targeting. The process of micellization in aqueous milieu is described in detail
      based on differences in the driving force of core segregation, including
      hydrophobic interaction, electrostatic interaction, metal complexation, and
      hydrogen bonding of constituent block copolymers. The segregated core embedded in
      the hydrophilic palisade is shown to function as a reservoir for genes, enzymes,
      and a variety of drugs with diverse characteristics. Functionalization of the
      outer surface of the polymeric micelle to modify its physicochemical and
      biological properties is reviewed from the standpoint of designing micellar
      carrier systems for receptor-mediated drug delivery. Further, the distribution of
      polymeric micelles is described to demonstrate their long-circulating
      characteristics and significant tumor accumulation, emphasizing their promising
      utility in tumor-targeting therapy. As an important perspective on carrier
      systems based on polymeric micelles, their feasibility as non-viral gene vectors
      is also summarized in this review article.

PMID- 11251250
TI  - US-guided fine needle aspiration versus coarse needle biopsy of thyroid nodules.
AB  - OBJECTIVE: The aim of this study was retrospectively to evaluate ultrasound (US)
      guided fine-needle aspiration (FNA), in combination with US-guided coarse-needle
      biopsies, (CNB) from solitary or dominant thyroid nodules routinely performed
      during a 2 year period. METHODS: Seventy seven patients were biopsied using US
      guided FNA and CNB. FNA was performed using a 21-Gauge needle and CNB using a 18
      Gauge single action spring-activated needle biopsy system. The biopsies were
      performed with local anaesthesia. The Department of Pathology routinely examined
      the biopsy specimens. The retrieval rate in obtaining material for diagnostic
      evaluation was FNA (97%), CNB (88%), FNA and CNB (100%). RESULTS: In all, 41 of
      the 77 patients underwent neck-surgery. The surgical specimens were used to
      determine the results of diagnosing neoplasia. The accuracy, sensitivity and
      specificity for FNA were 80, 83, and 77%. For CNB 86, 78, and 94%. For both FNA
      and CNB 80, 89 and 73%. The diagnostic value of the two methods showed no
      significant difference (P < 0.05). CNB revealed contrary to FNA, however, one
      additional cancer. Also a higher number of false positive findings was noticed
      using FNA. No serious complications were registered. Adequate biopsies were
      obtained in all the patients using the combination of US-guided FNA and CNB. No
      patient underwent rebiopsy. CONCLUSIONS: The study demonstrated that neither US
      guided CNB nor the combination of US-guided FNA and CNB were superior to US
      guided FNA. US-guided CNB is only recommended in few selected patients.

PMID- 11251251
TI  - Alterations in the peripheral circulation in patients with mild heart failure.
AB  - OBJECTIVE: In patients with severe heart failure, compensatory mechanisms fail to
      provide adequate blood supply to the peripheral circulation, especially when the
      metabolic need is increased. The aim of this study was to assess alterations in
      the peripheral circulation in patients with mild heart failure using ultrasound
      Doppler. METHODS: In 19 controls and in 11 patients with mild heart failure,
      Doppler spectra were recorded from the carotid, the brachial and the femoral
      artery at rest and, from the latter two arteries, during post-occlusive reactive
      hyperemia. Parameters derived from these Doppler spectra were used to make
      comparisons between both groups. RESULTS: At rest, the duration of the
      acceleration of blood was shorter in controls, the acceleration was steeper in
      controls and the deceleration duration was longer in controls as compared to the
      patients. Differences in the response to reactive hyperemia were only observed in
      the common femoral artery. CONCLUSIONS: In patients with mild heart failure,
      significant alterations in the peripheral circulation were observed especially
      for the femoral artery. These changes are caused by the impairment of the left
      ventricular function and by adjustments in the compensatory mechanism of the
      peripheral circulation.

PMID- 11251252
TI  - Three-dimensional ultrasonography of bone and soft tissue lesions.
AB  - BACKGROUND: The aim of this study was to investigate feasibility and potential
      applications of three-dimensional (3D) ultrasonography in the evaluation of
      musculoskeletal disorders. METHODS: 3D ultrasonography was performed in 83
      patients with bone (n = 50) or soft tissue lesions (n = 33). Volume data were
      obtained using two volume probes (1-8.5 and 8.5-12 MHz) and a 3D ultrasound unit.
      The results of 3D ultrasonography were compared to two-dimensional ultrasound and
      radiological imaging. RESULTS: The system enabled acquisition of 3D ultrasound
      data in diagnostic quality. 3D image-processing permits to analyse ultrasound
      data interactively in three orthogonal planes (section mode) or in realistic 3D
      views (rendering mode). Compared to conventional ultrasonography 3D image
      analysis improved assessment of details, provided better spatial orientation and
      facilitated image interpretation in 23, 44 and 49 cases, respectively. Additional
      findings that had significant influence on patient management were obtained in 16
      of 83 patients (19%). Multiplanar reformating provided additional scan planes and
      increased the comparability of follow up examinations by standardized display and
      measurement. 3D surface reconstructions were very helpful to understand the
      morphology of bone lesions e.g. tortuous fracture lines. CONCLUSION: Our
      preliminary experience shows that 3D ultrasonography of musculoskeletal disorders
      is feasible. The ability to assess previously unattainable scan planes and
      lifelike surface projections may be particularly valuable for imaging of bone
      lesions. Further studies will be required to assess the exact role of this new
      technique for the evaluation of musculoskeletal disorders.

PMID- 11251253
TI  - Anal sphincters defects--verification of the anal ultrasound diagnosis in
      'bimanual' examination.
AB  - The aim of this is to evaluate the diagnostic value of anal endosonography
      performed during pressing anterior wall of anal canal with a finger introduced
      into the lumen of vagina for the identification of anal sphincter defects. Anal
      ultrasound (AUS) with a finger introduced into the lumen of vagina was performed
      in a group of 55 women with anal sphincter defects recognized initially in
      standard AUS. This technique prevented false positive diagnoses of sphincter
      defects in 12 out of a group of 55 women (21.8%).

PMID- 11251254
TI  - Antenatal ultrasound diagnosis of perineal ectopic testis--a case report.
AB  - Perineal ectopia testis is a rare congenital anomaly with incidence of < 1% of
      all cases of undescended testes. We report a case of perineal ectopic testis
      detected by ultrasound at 38 weeks gestational age presenting as an oval
      echogenic structure located beneath the male fetal genitals. The diagnosis was
      confirmed postpartum by clinical examination and karyotyping of the neonate.
      Orchiopexy was performed 1 year after delivery.

PMID- 11251255
TI  - Sonographic detection of rhabdomyosarcoma of the urinary bladder.
AB  - Rhabdomyosarcoma (RMS) is the most common malignant pelvic tumor in the young
      child, occurring typically in children aged 2-4 years. It arises from the
      prostate or the trigone of the bladder in boys, and from the vagina or uterus in
      girls. We report a case of bladder rhabdomyosarcoma and discuss the
      ultrasonographic images. The mass produced filling defect on the contrast
      cystogram and also was demonstrated with CT.

PMID- 11251257
TI  - Use of ultrasound to improve the safety of postgraduate training in obstetrics
      and gynaecology.
AB  - Supervised clinical work is perhaps the most valuable component of postgraduate
      training and has a long-term impact. Senior clinicians not only take the
      responsibility of teaching and supervising junior doctors but also most of them
      take the consequences of any clinical failures or mistakes associated with the
      training. Despite the introduction of simulators and computer-assisted learning,
      practice on real patients is still required to learn many skills in obstetrics
      and gynaecology. Training must be safe, because trainees or trainers must not put
      our patients at risk as part of the process of learning to heal others.
      Ultrasound can be used to demonstrate and guide several procedures that have been
      performed 'blindly' in the past. This technology can reduce the risks associated
      with training and supervision of junior doctors.

PMID- 11251256
TI  - Left ventricular endocardial surface detection based on real-time 3D
      echocardiographic data.
AB  - OBJECTIVE: A new computerized semi-automatic method for left ventricular (LV)
      chamber segmentation is presented. METHODS: The LV is imaged by real-time three
      dimensional echocardiography (RT3DE). The surface detection model, based on level
      set techniques, is applied to RT3DE data for image analysis. The modified level
      set partial differential equation we use is solved by applying numerical methods
      for conservation laws. The initial conditions are manually established on some
      slices of the entire volume. The solution obtained for each slice is a contour
      line corresponding with the boundary between LV cavity and LV endocardium.
      RESULTS: The mathematical model has been applied to sequences of frames of human
      hearts (volume range: 34-109 ml) imaged by 2D and reconstructed off-line and
      RT3DE data. Volume estimation obtained by this new semi-automatic method shows an
      excellent correlation with those obtained by manual tracing (r = 0.992). Dynamic
      change of LV volume during the cardiac cycle is also obtained. CONCLUSION: The
      volume estimation method is accurate; edge based segmentation, image completion
      and volume reconstruction can be accomplished. The visualization technique also
      allows to navigate into the reconstructed volume and to display any section of
      the volume.

PMID- 11251258
TI  - Off-pump coronary artery bypass surgery. The beginning of the end?

PMID- 11251259
TI  - Off-pump coronary artery bypass surgery for critical left main stem disease:
      safety, efficacy and outcome.
AB  - OBJECTIVES: To determine whether patients with critical left main stem (LMS)
      coronary artery disease can undergo off-pump coronary artery bypass (OPCAB)
      surgery safely and successfully. METHODS: From May 1996 to March 2000 data for
      patients with critical (> or =50%) LMS stenosis who underwent conventional
      coronary artery bypass surgery with cardiopulmonary bypass (CCAB) or without
      (OPCAB) were collected prospectively using the Patient Analysis & Tracking
      System. A reusable pressure stabilizer, intra-coronary shunts and a single
      posterior pericardial stitch exposure technique were used in all OPCAB cases. Non
      randomized, retrospective data analysis included demographic and preoperative
      risk factors, operative details, clinical outcome and early follow-up. RESULTS:
      During the study period 387 patients with LMS stenosis underwent surgery (OPCAB
      n=75, CCAB n=312). Groups were similar in terms of preoperative and
      intraoperative variables although CCAB patients received significantly more
      grafts per patient (3.1+/-0.73 vs. 2.6+/-0.76, P< or =0.001). Mortality was
      similar in both groups (OPCAB 1.3% vs. CCAB 2.6%). OPCAB patients when compared
      to CCAB patients had a lower requirement for postoperative inotropes (12.0% vs.
      38.1%, P=0.0001), temporary postoperative pacing (2.7% vs. 10.1%, P=0.02), and
      blood product transfusion (6.7% vs. 31.4%, P<0.0001), a lower incidence of
      postoperative chest infection (0% vs. 6.7%, P=0.02) and a slightly reduced
      postoperative length of stay (7.9+/-5.46 vs. 8.3+/-5.11 days, P=0.01). At 24
      months follow-up, CCAB and OPCAB actuarial survival was 94.1+/-1.7% and 97.7+/
      2.3%, respectively. CONCLUSIONS: OPCAB surgery is safe and effective in patients
      with critical LMS disease.

PMID- 11251260
TI  - Outcome of non-elective coronary artery bypass grafting without cardio-pulmonary
      bypass.
AB  - OBJECTIVES: There is limited experience in the use of beating heart coronary
      artery bypass grafting (CABG) in emergency and urgent cases. The aim of this
      study was to retrospectively assess the safety and efficacy of this technique
      when used in a non-elective setting. METHODS: We retrospectively reviewed all
      urgent and emergency cases of coronary artery bypass grafting performed without
      cardiopulmonary bypass (CPB) from July 1999 to February 2000. There were 35
      patients in total. The mean age was 64.8+/-11.9. Twenty-six (74.3%) patients had
      Canadian Cardiovascular Society grade 4 angina. Twenty-six patients (74.3%) had
      triple vessel disease. Eleven patients (31.4%) were on preoperative IV nitrates
      and nine patients (25.7%) had a preoperative IABP (intra aortic balloon pump).
      Three patients (8.6%) had suffered a preoperative cardiac arrest during coronary
      angiography. Other associated significant risk factors were smoking (60%),
      hypertension (40%), hypercholesterolemia (57.1%) and previous Q wave myocardial
      infarction (31.4%). RESULTS: Twenty-two patients (62.9%) were classified as being
      urgent and 13 patients (37.1%) were classified as emergencies. The mean number of
      anastomoses performed were 2.8+/-0.8 (range 1-4) with 68.6% of patients under
      going triple or quadruple vessel grafting. All patients (100%) received at least
      one arterial graft. There was no conversion to cardiopulmonary bypass. The main
      postoperative complications were--supraventricular arrhythmias eight (22.9%), low
      cardiac output seven (20%) and postoperative HF/dialysis two (5.7%). The median
      postoperative intensive care unit (ICU) stay was 27.5 h. The mean postoperative
      hospital stay was 8.3+/-3.1 days. One patient died (2.9%) at the eighth day after
      surgery due to postoperative myocardial infarction, multi-organ failure secondary
      to the septicaemia and ventricular arrest. CONCLUSION: Non-elective CABG without
      CPB is feasible and safe with modern cardiac stabilization devices.

PMID- 11251261
TI  - Fatigue testing median sternotomy closures.
AB  - OBJECTIVE: Sternal dehiscence is commonly due to wire cutting through bone. With
      a biological model, we measured the rate of cutting through bone, of standard
      steel wire closure, peristernal steel wire, figure-of-eight closure, polyester
      and sternal bands sternotomy closure techniques. METHODS: Polyester, figure-of
      eight, peristernal and sternal band closures were tested against standard closure
      eight times using adjacent paired samples, to eliminate biological variables.
      Fatigue testing was performed by a computerized materials-testing machine,
      cycling between loads of 1 and 10 kg. The displacements at maximum and minimum
      loads were measured during each cycle. Cutting through, manifested by the
      displacement at the maximum load between the 1st and 150th cycles was measured.
      The percentage cut-through of each closure method versus standard closure was
      calculated. RESULTS: The differences in the displacement between each of the
      polyester (1.01 mm), figure-of-eight (0.52 mm), peristernal (0.72 mm) and sternal
      band (0.66 mm) groups versus standard closure (0.22, 0.22, 2.1, 3.2 mm) in the
      paired samples were statistically significant (Student's paired t-test; P<0.01).
      There were statistically significant differences in the percentage cut-through of
      polyester, figure-of-eight, peristernal and sternal bands (ANOVA, P<0.001),
      versus standard closure. CONCLUSIONS: In our sheep sternum model, we have
      quantified the differing rate of cutting through bone of five types of median
      sternotomy closure techniques. We have controlled for bone variables by testing
      each closure versus standard closure using paired adjacent bone samples.
      Peristernal and sternal band closure techniques are significantly superior to
      standard closure. The use of polyester and figure-of-eight closures requires
      caution.

PMID- 11251262
TI  - Vasoactive response of different parts of human internal thoracic artery to
      isosorbide-dinitrate and nitroglycerin: an in-vitro study.
AB  - OBJECTIVE: The left internal thoracic artery (LITA) is the most important graft
      for coronary artery bypass grafting (CABG). Its distal region is, however, prone
      to vasospasm. The effect of nitroglycerin (NTG) and isosorbide-dinitrate (ISDN)
      on different segments of this region was studied. METHODS: Rings of three
      segments of the LITA were studied: 6-9 mm proximal to the bifurcation (part A); 1
      3 mm proximal to the bifurcation (part B); and 3-6 mm distal to the bifurcation
      (part C). After baseline, maximal contraction of the rings was achieved using 60
      mmol/l of KCl, they were exposed to increasing doses of ISDN and NTG (10-100
      microg/ml), and dose-response curves were recorded. RESULTS: The contractile
      response of part A to KCl was significantly lower than that of parts B and C
      (1.87+/-0.25 versus 4.05+/-0.39 and 7.64+/-0.54 g, respectively; P<0.001). Both
      nitrates inhibited the contractile response in a concentration-dependent manner.
      The relaxing effects of both nitrates on part A was most pronounced (P<0.01),
      with the effect of ISDN being higher than that of NTG (P<0.01). CONCLUSIONS: The
      region 6-9 mm proximal to the LITA bifurcation is less prone to vasospasm, and
      has greater relaxation responses to ISDN and NTG than the more vasospastic distal
      parts of the LITA. We recommend avoiding the use of the very distal part of this
      artery during CABG, and to use high doses of ISDN rather than NTG as an anti
      spastic measure.

PMID- 11251263
TI  - Morbidity and mortality in patients waiting for coronary artery bypass surgery.
AB  - OBJECTIVES: To describe morbidity and mortality in patients waiting for coronary
      artery bypass graft (CABG) surgery and to assess determinants for the occurrence
      of these complications. METHODS: A prospective cohort study was carried out in a
      tertiary referral general teaching hospital. Three hundred and sixty consecutive
      patients with a priority of routine or urgent who were accepted for CABG or CABG
      with additional valve surgery were evaluated. Follow-up began from the moment of
      acceptance until the procedure took place for cardiac death, myocardial
      infarction and unstable angina requiring hospital admission. RESULTS: The median
      (25-75th percentile) waiting time in the two priority groups was 100 (79-119)
      days for the routine group and 69 (38-91) days for the urgent group. Overall,
      eight patients died, seven suffered a myocardial infarction, and 33 episodes of
      unstable angina requiring immediate hospitalization occurred. The majority of
      events took place during the first 30 days on the waiting list. Unstable angina
      less than 3 months before acceptance was identified as an independent predictor
      (hazard ratio 2.5, 95% confidence interval 1.2-5.1) for complications during the
      wait. The prognostic value of smoking and familial cardiovascular disease was
      found to vary depending on the priority assigned to the patient. CONCLUSIONS:
      Complications occur relatively early during the time on the waiting list. If
      complications in coronary heart disease cannot be predicted more accurately, the
      only way to diminish the complication rate is drastic reduction of waiting times.

PMID- 11251264
TI  - The radial artery in coronary re-operations.
AB  - OBJECTIVES: Vein graft (VG) failure often leads to coronary re-operation (re-do
      coronary artery bypass grafting (CABG)). As the internal thoracic artery (ITA(s))
      and VG have often already been used and as the VG has usually failed, the radial
      artery (RA) is ideally suited for use in re-do CABG. We evaluated our experience
      where the RA(s) was a key conduit in re-do CABG to determine the safety and
      efficacy and compared this to re-operations where the RA was not used. METHODS:
      Three hundred and fifty-two consecutive patients who had re-do CABG using the
      RA(s) from July 1995 to March 1999 were studied: mean age 67.3 years, 209 (60%)
      angina Class III or IV, past acute myocardial infarction (AMI) in 201 (57%), left
      ventricular ejection fraction <50% in 109 (31%). Five hundred and thirty-two RAs
      were used (bilateral in 180 (51%) patients). Additionally, 232 new left ITAs (66%
      of patients) and 71 new right ITAs (20% of patients) were placed. A total of 1022
      distal anastomoses were performed (mean of 2.9 per patient). Follow-up was at 1
      month, 3 months, and yearly. The results were also compared to 730 patients
      having re-do CABG without an RA (January 1990 to June 1995) using identical
      operative and myocardial protection techniques. RESULTS: RA spasm was noted intra
      operatively in four (1.1%) patients, operative mortality was noted in 14 (3.9%)
      patients, peri-operative myocardial infarction was noted in ten (2.8%) patients,
      intra-aortic balloon pump was used in nine (2.6%) patients, stroke was noted in
      six (1.7%) patients, deep sternal infection was noted in two (0.6%) patients, and
      re-operation for haemorrhage was performed in seven (2.0%) patients. There was
      only one (0.3%) forearm infection, and two (0.6%) forearm haematomas required
      drainage. There was no hand ischaemia. When compared to 730 re-do CABG patients
      without RA, there were significant differences in arterial grafts used (2.6 vs.
      1.2, P=0.01), in deep sternal infection (0.6% vs. 2.6%, P=0.01) and donor site
      infection (0.3% vs. 2.7%, P=0.005) favouring the RA group. Three-year actuarial
      survival was 89.2% in the RA group and 88.5% in the non-RA group (P=1.0).
      CONCLUSIONS: Use of the RA in re-do CABG is safe, effective, allows additional
      conduit choice, reduces donor site and sternal infections, and may avoid further
      late VG failure.

PMID- 11251265
TI  - Graft dilation after redo surgery for aneurysm formation following patch
      angioplasty for aortic coarctation.
AB  - OBJECTIVES: Aneurysm formation after patch angioplasty for aortic coarctation is
      a frequent and potentially lethal complication, necessitating surgical
      reintervention. Although several mechanisms have been postulated, flow
      disturbance in a concomitant hypoplastic transverse aortic arch most likely
      contributes to the aneurysm formation. The outcome of the grafts after redo
      surgery, however, is unknown. The purpose of this study was to evaluate the
      outcome of the inserted graft in patients with surgery for aneurysm formation
      following patch angioplasty for coarctation of the aorta. METHODS: In 16 patients
      redo surgery was performed for aneurysm formation (diameter: 47.1+/-11.9 cm)
      (mean+/-SD), 12.7+/-2.1 years after the initial patch angioplasty. All patients
      had a concomitant arch hypoplasia. They were treated by insertion of a Dacron
      Gelseal graft (16-30 mm), but the associated hypoplastic arch segment was left
      untouched. To evaluate the evolution of the new graft, patients were followed by
      means of magnetic resonance (MR) imaging. RESULTS: The immediate postoperative
      outcome was uneventful in 12 patients. Four patients, however, suffered from a
      recurrent nerve paralysis and one of them of a spinal cord transection. The mean
      follow-up time was 54.1+/-17.9 months during which 59 magnetic resonance studies
      were performed. The number of MR studies per patient ranged from two to seven.
      The graft diameter increased significantly with 56+/-18%, range 20-82 (P<0.0001).
      This widening was most pronounced within the first year after surgery (43+/-16%,
      range 5-67) (P<0.0001). CONCLUSIONS: Flow acceleration caused by an even mild
      hypoplastic transverse arch can put excessive strain on the distal part of the
      aortic arch. This can lead not only to aneurysm formation after patch angioplasty
      but also to excessive dilation of the Dacron Gelseal graft. At intermediate long
      term follow-up, however, a stabilization of the graft dilation is observed.

PMID- 11251266
TI  - Outcome following tricuspid valve detachment for ventricular septal defects
      closure.
AB  - OBJECTIVES: Detachment of the septal leaflet of the tricuspid valve from the
      annulus (TVD) has been used to improve visualization of ventricular septal
      defects (VSDs), but may be associated with increased operative time, heart block,
      and the development of tricuspid regurgitation (TR). METHODS: Patients undergoing
      VSD closure between 1/1/96 and 31/12/99 were retrospectively reviewed. Follow-up
      was obtained from the patients' cardiologists. RESULTS: Transatrial VSD closure
      was performed in 172 patients with TVD in 36 (21%) at the surgeon's discretion.
      The leaflet incision was repaired with a separate suture (22) or with the VSD
      patch suture (14). Additional procedures including arch augmentation, closure of
      atrial septal defects, and closure of additional VSDs were performed in 93 (68%)
      non-TVD patients and 20 (56%) TVD patients. The median age was 6.2 months (range
      1 day to 46 years) and the median weight was 5.9 kg (range 1.5-71.5 kg).
      Cardiopulmonary bypass (CPB) time was 64+/-24 min and cross-clamp time was 34+/
      16 min. One hospital death occurred in an infant with tracheal stenosis. No child
      in either group developed complete heart block. The median duration of
      postoperative stay was 4 days (range 2-49 days). There were no differences in CPB
      time, cross-clamp time or postoperative stay between the TVD and non-TVD groups
      (P>0.1 for all). At a mean follow-up of 17+/-15 months, there have been two late
      deaths unrelated to cardiac disease. No child in the TVD group required
      reoperation for residual VSD, compared to three in the non-TVD group. No child in
      the TVD group has greater than mild TR, but six in the non-TVD group have greater
      than mild TR. No child in either group has undergone reoperation for TR.
      CONCLUSIONS: TVD is a safe, effective technique to improve visualization of VSD
      and is not associated with heart block, increased operative time, or TR. TVD may
      result in improved preservation of tricuspid valve architecture and decrease the
      incidence of significant postoperative TR.

PMID- 11251267
TI  - Results of the Lecompte procedure in malposition of the great arteries and
      pulmonary obstruction.
AB  - OBJECTIVE: Assessment of the Lecompte procedure, our repair method of choice in
      malposition of the great arteries with pulmonary stenosis. METHODS: A
      retrospective analysis of 42 patients (median age at operation, 1.4 years)
      operated on between 1986 and 1999 for various forms of great artery malposition,
      ventricular septal defect, and pulmonary stenosis. Relevant associated findings
      included the insertion of a tricuspid papillary muscle on the conal septum (nine
      patients), absence of conal septum (six patients), hypoplasia of a side pulmonary
      artery (four patients), and hypoplasia of the right ventricle (one patient). A
      preliminary systemico-pulmonary shunt was created in 28 patients and a cavo
      pulmonary anastomosis in one patient. At operation, the conal septum (whenever
      present) was resected (36 patients), the pulmonary bifurcation was usually
      translocated over the ascending aorta (37 patients), and the main pulmonary
      artery was enlarged with a patch of pericardium. A monocusp valve was fashioned
      within the patch in 40 patients. The follow-up information was complete in 32
      patients and ranged from 0.4 to 14 years (mean, 5.4+/-3.2 years). RESULTS: The
      survival rate at 5 years was 92+/-5%. Three patients died post-operatively
      (mortality, 7%) and none during follow-up. The freedom from reoperation was 86+/
      8 and 51+/-22% at 5 and 10 years, respectively. Six patients were reoperated, all
      for a pulmonary stenosis. Calcification of the monocusp patch was present in all.
      Pulmonary stenosis developed in three further patients: one underwent
      percutaneous dilatation and two are awaiting surgery. No procedural factors
      thought to have a potential correlation with the development of right ventricular
      outflow tract stenosis could be individualized on univariate analysis.
      CONCLUSIONS: The Lecompte procedure, which allows early repair of these defects,
      provides overall good results. The need to reoperate on the right or left
      ventricular outflow tract seems reduced in comparison with the Rastelli
      operation, the other alternative.

PMID- 11251268
TI  - A minimal transverse incision with low median sternotomy for pediatric congenital
      heart surgery.
AB  - OBJECTIVES: Median sternotomy is the incision of choice for most cardiac surgical
      procedures, but the full-length vertical skin incision generally leaves an
      unsightly scar. In certain patients undergoing short, low-risk procedures,
      cosmetic considerations are of relatively greater importance. METHODS: A minimal
      transverse curvilinear skin incision with low median sternotomy is described
      which gives adequate exposure for selected open-heart procedures. Since September
      1997, this approach has been used in 22 pediatric patients undergoing open-heart
      surgery including five cases of Fallot's tetralogy. We also compared the
      operation time and result with other approaches. RESULTS: Using this modified
      method, the exposure of the heart was good enough, and there were no difficulties
      in cannulating the ascending aorta for cardiopulmonary bypass. Although it took a
      longer time to close the wound, the operation time was similar to the standard
      approach. The small transverse wound was not visible under conventional clothes.
      CONCLUSIONS: A minimal transverse incision with low median sternotomy provides an
      alternative approach for small wound open-heart surgery in patients with a simple
      congenital cardiac defect. It is technically feasible and has a good cosmetic
      result.

PMID- 11251269
TI  - Is there a role for extracorporeal life support after stage I Norwood?
AB  - OBJECTIVES: Controversy still surrounds the use of extracorporeal life support
      (ECLS) in patients with single ventricle physiology. An analysis of the
      experience with a group of neonates who underwent stage I Norwood palliation and
      received ECLS is reported. METHODS: A retrospective review of hospital records,
      operative notes and perfusion data was performed in a group of 12 consecutive
      patients undergoing ECLS in the perioperative period after stage I. An analysis
      to identify risk factors for poor outcome was performed. RESULTS: The mean age
      and weight were 3.9 days (1-14) and 2.6 kg (1.4-3.8), respectively. There were
      3/12 patients under 2.5 kg and four patients were under 35 weeks of gestation.
      The most common diagnosis (7/12) was hypoplastic left heart syndrome with aortic
      atresia. Associated extracardiac anomalies were present in four patients. Three
      patients had an additional cardiac defect and two of these required an additional
      surgical procedure besides the stage I Norwood. The mean circulatory arrest was
      56 min (46-63). ECLS was initiated preoperatively in one, intraoperatively in
      nine, and postoperatively in two patients. The indication for support was:
      arrhythmia (one), low output (six), cardiac arrest (three), unbalanced
      circulation (one), and hypoxemia (two). The mean duration of support was 68 h (24
      192). Eight patients were weaned off support, and six were discharged home in
      good condition. Morbidity included sepsis in five, renal failure in five,
      neurologic sequelae in three, and bleeding in two. Prematurity, renal dysfunction
      and the initiation of ECLS outside the operating room were significantly
      associated with poor outcome. Residual hemodynamic effect, low birth weight and
      neurologic event showed a tendency towards poor outcome, but did not reach
      statistical significance. CONCLUSIONS: Although the use of ECLS in patients with
      single ventricle physiology still carries a significant risk, prompt initiation
      of support can improve the outcome in a group of patients with impaired
      cardiopulmonary function after stage I palliation.

PMID- 11251270
TI  - Expanded polytetrafluoroethylene membranes to wrap surfaces of circulatory
      support devices in patients undergoing bridge to heart transplantation.
AB  - OBJECTIVE: Because of a lack of donor hearts, an increasing number of patients
      with heart failure must now undergo bridge to cardiac transplantation with a
      mechanical circulatory support device. Moreover, support periods have become
      longer. As a result, pericardial adhesions may develop while the support device
      is implanted, increasing the risk of injury at resternotomy and bleeding after
      transplantation. Use of expanded polytetrafluoroethylene (ePTFE) pericardial
      substitutes (membranes) may prevent such adhesions. PATIENTS AND METHODS: From
      January 1997 to December 1999, ePTFE membranes were used in 23 patients to wrap
      portions of an implanted left ventricular assist device (LVAD) or total
      artificial heart (TAH). Any complications during mechanical support or at cardiac
      transplantation were recorded. Six ePTFE membranes removed at transplantation
      were studied histologically. RESULTS AND CONCLUSIONS: At resternotomy for
      transplantation, the plane of dissection between tissues, ePTFE membranes, and
      surfaces of the mechanical support device were easily discerned. No adhesions
      were observed between tissues and membranes. There were no injuries during
      resternotomy and no patient had to undergo reoperation because of bleeding. One
      patient given a TAH had an infection during circulatory support that was
      controlled by antibiotic therapy. In another patient, clots developed between the
      device and an ePTFE membrane; these were removed successfully. Histologic studies
      of removed ePTFE membranes showed no infiltration of the membranes interstices by
      collagen or cellular components. Use of ePTFE membranes in patients undergoing
      bridge to transplantation with either an LVAD or a TAH limited adhesions between
      tissues and device surfaces without increasing the risk of infection.

PMID- 11251271
TI  - Systemic embolism: a serious complication after cardiac transplantation avoidable
      by bicaval technique.
AB  - OBJECTIVE: Systemic embolism is a serious complication after classical orthotopic
      transplantation, presumably originating from enlarged left atrium. We
      specifically studied this problem after classical and modified bicaval
      transplantation. METHODS: Between December 1985 and March 1999 we consecutively
      performed 72 classical and 106 modified heart transplantation. Modification
      included bicaval anastomosis and recipient left atrium maximal reduction. Mean
      age was 47 years. All the patients received an antiplatelet therapy and were
      routinely followed. When clinical signs of systemic embolism were present, a
      neurological evaluation and transesophageal echocardiography were done. Sixty
      matched patients (30 of each group) had comparative transesophageal
      echocardiography study, at least 6 months after transplantation. RESULTS:
      Perioperative mortality was 17.4%. Mean follow-up was 6.8 2+/47 years. All
      patients were in sinus rhythm. Among 147 survivors, 11 patients who underwent
      classical transplantation had a systemic embolism, 1 month to 12 years after
      transplantation, 15.3%, (11/72). Two limb ischemia and one mesenteric ischemia
      (needing surgery), seven strokes (one death, two permanent neurological deficit).
      There was no systemic embolism in the modified technique group (P=0.013). Left
      atrial comparative transesophageal echocardiography study showed a larger left
      atrial surface in classical transplantation. 33+/-4 cm(2) versus 20+/-3 cm(2) in
      a modified technique, P=0.01. Spontaneous echo contrast was present in 56% of
      classical technique group associated with atrial thrombosis in nine patients,
      there were no atrial thrombosis in modified technique group and spontaneous
      echocontrast was present in 0.5% (P=<0.001). CONCLUSION: The occurrence of
      systemic embolism, left atrial spontaneous echocontrast and thrombosis when using
      classical technique, and the absence of these complications with the bicaval
      technique justified the use of this method. Our experience with atrial thrombosis
      and spontaneous echocontrast rises the question of anticoagulation in classical
      transplantation.

PMID- 11251272
TI  - Norepinephrine release after acute brain death abolishes the cardioprotective
      effects of ischemic preconditioning in rabbit.
AB  - OBJECTIVE: Brain death (BD) abolishes the infarct-limiting effect of ischemic
      preconditioning (IP) in rabbits. We wished to define the role of the
      norepinephrine storm in this observation. METHODS: Rabbits were randomized into
      six groups of ten animals each. In control group (CTRL), anaesthetized rabbits
      were subjected to 30 min left coronary marginal branch occlusion and 90 min
      reperfusion. In CTRL+IP group, anaesthetized rabbits were preconditioned with a 5
      min ischemia and 5-min reperfusion sequence before coronary occlusion. In
      CTRL+NE+IP group, anaesthetized rabbits received a 10 microg/kg norepinephrine
      injection 90 min before IP. In BD group, rabbits were subjected to 90 min of BD
      before coronary occlusion. In BD+IP group, brain-dead rabbits were preconditioned
      before coronary occlusion. In BD+LA+IP group, rabbits received an intra-arterial
      bolus injection of an alpha and beta adrenoreceptor blocking agent (labetolol, 1
      mg/kg) prior to brain death induction and subsequent preconditioning. BD was
      induced by rapid inflation of an intracranial balloon. At termination of the
      experiment, left ventricular volume (LVV), myocardial volume at risk (VAR) and
      infarct volume (IV) were determined with methylene blue and tetrazolium staining,
      and measured using planimetry. RESULTS: LVV was not significantly different among
      groups. Myocardial VAR/LVV was not significantly different between groups (CTRL,
      22.5+/-6.9%; CTRL+IP, 23.3+/-2.2%; CTRL+NE+IP, 25.9+/-12.7%; BD, 19.9+/-4.8%;
      BD+IP, 21.7+/-3.1%; BD+LA+IP, 23.4+/-5.8%; P=NS). IV/VAR was significantly
      reduced in the CTRL+IP group as compared with CTRL and CTR+NE+IP groups (12.2+/
      1.2 vs. 49.7+/-1.7 and 49.3+/-4.7%; P<0.0001). There was no significant
      difference in IV/VAR between BD and BD+IP groups. In contrast, IV/VAR was reduced
      in BD+LA+IP compared to BD and BD+IP groups (13.9+/-5.4 vs. 50.0+/-1.4 and 49.6+/
      1.5%; P<0.001). CONCLUSION: The loss of infarct-limiting effect of IP in brain
      dead rabbits is related to the massive release of norepinephrine that occurs as a
      consequence of BD.

PMID- 11251273
TI  - Investigations on the new free radical scavenger polynitroxyl-albumin to prevent
      ischemia and reperfusion injury after orthotopic heart transplantation in the pig
      model.
AB  - OBJECTIVE: Nitroxides have strong antioxidant capacity but their effectiveness is
      limited by their rapid intracellular inactivation. Polynitroxyl-Albumin (PNA) is
      capable of regenerating inactivated nitroxide. We tested the effect of PNA
      against reperfusion injury in heart transplantation. METHODS: Pig hearts were
      transplanted orthotopically. In the control group (n=9) reperfusion was performed
      without reperfusion modifications. In the experimental group (n=10) 1 ml/kg PNA
      was given before cross-clamp release. RESULTS: Hemodynamic performance was
      impaired after transplantation in both groups without significant intergroup
      differences. Plasma malonedialdehyde levels were significantly diminished in the
      PNA group as compared to the controls. CK-MB levels in both groups were increased
      within the first 2 h of reperfusion without significant intergroup differences.
      In contrast, there were found significant higher values of myocardial specific
      lactate dehydrogenase (LD1) in the controls versus PNA group. CONCLUSIONS: PNA
      was able to reduce lipid peroxidation and attenuate free radical activity.
      Contractile dysfunction could no be improved, indicating that (a) the radical
      scavenging effect was to weak or (b) other mechanisms than free oxygen radicals
      are responsible for myocardial damage in this experimental model.

PMID- 11251275
TI  - A comparative study of Euro-Collins, low potassium University of Wisconsin and
      cold modified blood solutions in lung preservation in acute autotransplantations
      in the pig.
AB  - OBJECTIVE: The aim of the study was to assess the quality of lung preservation
      offered by Euro-Collins solution (EC), Cold Modified Blood solution (CMB) and low
      potassium University of Wisconsin solution (UWLP). METHOD: Fifteen right lung
      auto-transplantations (five for each solution) in the pig (Large White) were
      performed after 2 h of cold ischaemic storage in physiological solution at 4
      degrees C. Right lung biopsies were performed before ischaemia and 30 min after
      reperfusion, for histoenzymatic, histopathological and electron microscope
      studies. RESULTS: After reperfusion, significant alterations were observed in the
      haemodynamics with only the right lung perfused; pulmonary arteriolar resistance
      increased by a factor of 5 in the EC group, by a factor of 4 in the CMB group and
      by a factor of 1.2 in the UWLP group; the right ventricular ejection fraction
      fell by 60% in the EC group, by 50% in the CMB group and by 31% in the UWLP
      group. Haemodynamic impairment was lower in the UWLP group (P<0.05; P<0.001) as
      was ischaemic-reperfusion injury (P<0.05). Oedema was observed in the EC group
      and extensive alveolar wall damage in the CMB group. Hypoxaemia was observed in
      all groups but the differences in the degree of hypoxaemia were not significant.
      CONCLUSIONS: The authors concluded that UWLP solution was the most effective of
      the three in this transplant model.

PMID- 11251274
TI  - Bronchial artery perfusion during cardiopulmonary bypass does not prevent
      ischemia of the lung in piglets: assessment of bronchial artery blood flow with
      fluorescent microspheres.
AB  - OBJECTIVE: Blood supply of the lungs during total cardiopulmonary bypass (CPB) is
      limited to flow through the bronchial arteries. This study was undertaken to
      assess the bronchial artery blood flow during CPB with fluorescent microspheres
      in a piglet model. METHODS: We subjected ten piglets (mean weight 5.0+/-0.5 kg)
      to 120 min of normothermic, total CPB without aortic cross-clamping, followed by
      60 min of post-bypass perfusion. Fluorescent microspheres were injected into the
      left atrium or the aortic cannula or distal to the cannula to assess bronchial
      artery blood flow before, during and after CPB. The reference samples were taken
      from the descending aorta. We compared the different sites of injection. Tissue
      samples of the lungs were taken before and 60 min after CPB. RESULTS: Before CPB,
      total bronchial artery perfusion was 43.6+/-14.1 ml/min (4.8+/-1.3% of cardiac
      output) as by injection distal to the aortic cannula. These values were not
      different when microspheres were injected into the left atrium or the aortic
      cannula. There was no difference in scatter or in the amount of microspheres in
      the reference samples among the three injections sites. During CPB, bronchial
      artery perfusion was significantly decreased (4.4+/-2.4 ml/min vs. 40.0+/-5.0
      ml/min before CPB) and returned to baseline values 60 min after CPB. Light
      microscopy of the tissue samples revealed alveolar septal thickening and a
      decrease in alveolar surface area after 60 min of reperfusion which was
      associated with a decreased capacity to oxygenate blood. CONCLUSIONS: (1)
      Bronchial artery blood flow can quantitatively be assessed during CPB when
      microspheres are injected into the ascending aorta and the reference samples are
      taken from the descending aorta. (2) Despite adequate perfusion pressure
      bronchial artery blood flow is decreased substantially during CPB. (3) The
      decrease in blood flow and the ultrastructural changes present at the end of CPB
      suggest the presence of low-flow ischemia of the lung during total CPB.

PMID- 11251276
TI  - Tracheal cancer in Denmark: a nationwide study.
AB  - OBJECTIVE: Most published series on tracheal cancer reflect single institution
      experiences. We used the nationwide Danish Cancer Registry to report on
      characteristics and treatment of tracheal cancers in Denmark. METHODS: One
      hundred and nine cases of primary tracheal cancers were extracted from the
      registry in the period 1978-1995. The clinical data, histological distribution
      and treatment modalities were analyzed. The cancers were staged in four groups
      (stage I-IV) according to size, location and spread. RESULTS: Seventeen cases
      were diagnosed at autopsy. Ninety-two cases were diagnosed in vivo and 84% of
      these within 3 months after the first consultation. Sixty-three percent of the
      cancers were squamous cell carcinomas and only 7% were adenoid cystic carcinomas.
      The disease was at stage I in 21%, stage II in 23%, stage III in 6% and stage IV
      in 50%. The majority of the patients received radiotherapy as single treatment.
      Only nine patients were offered surgery (six were resected and three were found
      inoperable). The overall survival rates for cases diagnosed in vivo were 1-year
      32%, 2-year 20% and 5-year 13%. For the resected patients the 5- and 15-year
      survival rates were 50%. CONCLUSIONS: Tracheal cancers were rare and adenoid
      cystic carcinomas not as frequent as generally believed. Surgery was rarely
      offered. A resectability rate of only 10% is not adequately explained by
      selection bias and indicates a nihilistic attitude based on ignorance about
      surgical treatment of tracheal cancers. A more dedicated and aggressive approach
      with centralized workup and radical treatment is strongly recommended.

PMID- 11251277
TI  - Trimodality management of malignant pleural mesothelioma.
AB  - OBJECTIVE: We reviewed our experience with trimodality management of malignant
      pleural mesothelioma (MPM). METHODS: From September 1998 to August 2000, 32
      consecutive patients with histological diagnosis of MPM underwent trimodality
      therapy, including surgery followed by adjuvant chemotherapy and radiation
      therapy. Surgery consisted of pleurectomy/decortication (P/D) or pleural
      pericardial-pneumonectomy and diaphragm (PPPD). Pre-operative staging according
      to the Brigham Staging System was accomplished using computed tomography (CT) and
      magnetic resonance imaging (MRI); patients with evident extrapleural spread were
      excluded. RESULTS: Our series included 21 men and 11 women with a median age of
      53.5 years (range 40-69). Histologically, there were 26 epithelial, four mixed
      and two sarcomatous MPM. Post-surgical staging was as follows: six patients were
      at Stage I; of these, two received a P/D and four a PPPD. Ten patients were at
      Stage II and all received a PPPD; 16 patients were at Stage III (under-staged pre
      operatively): of these, nine patients presented extrapleural lymph node
      metastases (N2) and all received a PPPD, seven patients presented with chest wall
      or mediastinal invasion (T4) with macroscopic residual tumour, and all received a
      de-bulking P/D. We observed major complications in ten patients: six bleeding,
      two respiratory insufficiency and two nerve paralysis. There were two
      perioperative deaths (6.25% mortality). Twenty-seven patients out of 30 surviving
      surgery had a follow-up greater than 6 months; 21 patients out of 27 are alive
      with a median follow-up of 12.5 months. CONCLUSIONS: (1) Trimodality therapy is
      feasible in selected patients with MPM and has an acceptable operative mortality
      rate. (2) Our current pre-operative staging based on CT/MRI looks rather
      inaccurate and needs to be improved. (3) The high rate of post-surgical N2
      patients or with diffusion to the inferior surface of the diaphragm may suggest
      the use of routine mediastinoscopy and laparoscopy for a more appropriate patient
      selection.

PMID- 11251278
TI  - Utility of standardized exercise oximetry to predict cardiopulmonary morbidity
      after lung resection.
AB  - OBJECTIVES: To evaluate if desaturation, measured by finger oximetry on
      standardized exercise, accurately predicts cardiopulmonary morbidity after
      pulmonary resection. METHODS: A prospective observational clinical study was
      carried out on 81 consecutive lung carcinoma patients scheduled for pulmonary
      resection from February 1998 to March 1999. Finger oximetry was monitored during
      an incremental to exhaustion cycle exercise test. The presence or absence of
      desaturation (cut-off value 90%) during exercise was recorded. Other independent
      analyzed variables were: age of the patient (over 75th percentile), body-mass
      index (BMI) (over 75th percentile), presence of major cardiovascular co
      morbidity, and calculated postoperative FEV1% (under 25th percentile) according
      to the number of resected segments (ppoFEV1%). Postoperative cardiopulmonary
      morbidity was the evaluated dependent outcome. Fisher's exact test and risk
      calculation on contingency tables were used for statistical analysis. RESULTS: A
      lobectomy was performed in 62 cases, a pneumonectomy was performed in 16 cases,
      and a segmentectomy was performed in three cases. The mean age of the patients
      was 63.6 years (SD 10.3, range 34-79 years, 75th percentile 72 years), the mean
      BMI was 25.9 (SD 4.9, range 16.9-38.1, 75th percentile 29.3), and the mean
      ppoFEV1% was 64.1 (SD 2016.1, range 29.5-98.6, 25th percentile 50.5). In 14
      patients exercise desaturation was registered. Postoperative cardiopulmonary
      morbidity was presented in 32 cases (five deaths). No correlation was found
      between postoperative morbidity and any of the following variables: age of the
      patient, BMI, and co-morbidity. On univariate analysis only low ppoFEV1%
      (P<0.001) was associated with the outcome, so no multivariate analysis has been
      carried out. CONCLUSIONS: We have shown that desaturation during standardized
      exercise in this series adds no relevant information to predict postoperative
      cardiorespiratory morbidity after lung resection.

PMID- 11251279
TI  - Incidence of chronic pain after minimal-invasive surgery for spontaneous
      pneumothorax.
AB  - OBJECTIVE: Recently, it has been shown that minimal-invasive surgical procedures
      like operations for spontaneous pneumothorax result in a reduction of pain in the
      immediate postoperative course. However, little is known on the influence of
      minimal-invasive thoracic surgery on long term disability. Therefore, we analyzed
      the incidence of chronic pain in patients after minimal-invasive operation for
      primary (PSP) or secondary (SSP) spontaneous pneumothorax. METHODS: In the study
      included were 78 patients (PSP: n=59; SSP: n=19; male: 58, female 20) who had
      been treated at our institution between 1992 and 1995. The median age was 37
      years (range: 17-84). The patients were interviewed by a standardized
      questionnaire or alternatively by phone or in the outpatient clinic. Complete
      follow up data were obtained from 60 patients which were further analyzed.
      RESULTS: After a median follow up of 59 months (range 35-79) 41 (68.3%) patients
      were completely free from any complaints. However 19 (31.7%) patients suffered
      from chronic pain. Two of them (3.3%) required daily oral pain medication. The
      incidence of chronic complaints was more frequent in patients with pleurectomy
      (47.1%) as compared to patients with mechanical pleurodesis only (25.6%;
      P=0.107). On a visual analog pain scale (ranging from 0 to 100) five (8.3%)
      patients described a pain intensity <10, 12 (20%) patients between 10 and 20 and
      two (3.3%) patients >50. In the majority of the patients the pain was located in
      the area of the trocar incisions. Six (10%) patients had a chronic complaints in
      the ipsilateral shoulder. CONCLUSIONS: The incidence of chronic postoperative
      complaints after minimal-invasive procedures for spontaneous pneumothorax is
      relatively high. This has to be considered if minimal-invasive procedures are
      discussed to be an alternative to simple drainage therapy for the first episode
      of spontaneous pneumothorax.

PMID- 11251280
TI  - Post-traumatic hernia of the lung.

PMID- 11251281
TI  - Intramuscular lipoma of the intercostal muscle--the source of hour-glass
      transmural thoracic lipomas?

PMID- 11251282
TI  - Coronary artery bypass grafting after pneumonectomy.
AB  - The need to perform coronary artery bypass grafting in patients who have a single
      lung is not uncommon. To date, the safety of such procedures has not been well
      documented. In this article, we review the literature using the Medline 1966 to
      September 2000 database to identify patients with pneumonectomy who underwent
      coronary artery grafting and we provide a compilation of all reported cases. We
      also present an additional case in whom the use of nasal bilevel positive airway
      pressure was beneficial in preventing postoperative pulmonary complications.

PMID- 11251283
TI  - Cardiogenic shock due to metastatic cardiac lymphoma: still a diagnostic and
      therapeutic challenge.
AB  - Myocardial involvement by metastatic lymphoma progressively leads to severe
      contractile impairment and fatal outcome. Correct diagnosis is often late due to
      misleading presentation signs. We report on a case of extensive cardiac
      involvement of a T-cell thymic lymphoma in a young woman, necessitating emergent
      extracorporeal membrane oxygenation (ECMO) circulatory support, with satisfactory
      hemodynamic recovery and subsequent ECMO weaning. Unfortunately, the following
      clinical course was rapidly fatal. This case seems to confirm that early
      aggressive instrumental diagnosis is crucial before severe myocardial impairment
      can prevent any therapeutic option. Extensive use of transesophageal
      echocardiographic examination and early endomyocardial biopsy are highly
      recommended.

PMID- 11251284
TI  - The freestyle stentless aortic bioprosthesis: more about the subcoronary
      technique.
AB  - Two years after aortic valve replacement with a Freestyle stentless aortic
      xenograft using the partial scallop inclusion technique, late prosthetic valve
      endocarditis developed with abscess formation in the space between the porcine
      and native human aortic wall. The presence of such a periprosthetic dead space
      exposes the patient to increased postoperative pressure gradients and the risk of
      superinfection.

PMID- 11251286
TI  - Getting gene therapy under control. ARIAD Pharmaceuticals, Inc.

PMID- 11251285
TI  - Protein microarrays: prospects and problems.
AB  - Protein microarrays are potentially powerful tools in biochemistry and molecular
      biology. Two types of protein microarrays are defined. One, termed a protein
      function array, will consist of thousands of native proteins immobilized in a
      defined pattern. Such arrays can be utilized for massively parallel testing of
      protein function, hence the name. The other type is termed a protein-detecting
      array. This will consist of large numbers of arrayed protein-binding agents.
      These arrays will allow for expression profiling to be done at the protein level.
      In this article, some of the major technological challenges to the development of
      protein arrays are discussed, along with potential solutions.

PMID- 11251287
TI  - New fluorescent probes for the measurement of cell membrane viscosity.
AB  - BACKGROUND: Molecular rotors are fluorescent molecules that exhibit viscosity
      dependent fluorescence quantum yield, potentially allowing direct measurements of
      cell membrane viscosity in cultured cells. Commercially available rotors,
      however, stain not only the cell membrane, but also bind to tubulin and migrate
      into the cytoplasm. We synthesized molecules related to 9-(dicyanovinyl)
      julolidine (DCVJ), which featured hydrocarbon chains of different length to
      increase membrane compatibility. RESULTS: Longer hydrocarbon chains attached to
      the fluorescent rotor reduce the migration of the dye into the cytoplasm and
      internal compartments of the cell. The amplitude of the fluorescence response to
      fluid shear stress, known to decrease membrane viscosity, is significantly higher
      than the response obtained from DCVJ. Notably a farnesyl chain showed a more than
      20-fold amplitude over DCVJ and allowed detection of membrane viscosity changes
      at markedly lower shear stresses. CONCLUSIONS: The modification of molecular
      rotors towards increased cell membrane association provides a new research tool
      for membrane viscosity measurements. The use of these rotors complements
      established methods such as fluorescence recovery after photobleaching with its
      limited spatial and temporal resolution and fluorescence anisotropy, which has
      low sensitivity and may be subject to other effects such as deformation.

PMID- 11251288
TI  - Selective in vitro glycosylation of recombinant proteins: semi-synthesis of novel
      homogeneous glycoforms of human erythropoietin.
AB  - BACKGROUND: A natural glycoprotein usually exists as a spectrum of glycosylated
      forms, where each protein molecule may be associated with an array of
      oligosaccharide structures. The overall range of glycoforms can have a variety of
      different biophysical and biochemical properties, although details of structure
      function relationships are poorly understood, because of the microheterogeneity
      of biological samples. Hence, there is clearly a need for synthetic methods that
      give access to natural and unnatural homogeneously glycosylated proteins. The
      synthesis of novel glycoproteins through the selective reaction of glycosyl
      iodoacetamides with the thiol groups of cysteine residues, placed by site
      directed mutagenesis at desired glycosylation sites has been developed. This
      provides a general method for the synthesis of homogeneously glycosylated
      proteins that carry saccharide side chains at natural or unnatural glycosylation
      sites. Here, we have shown that the approach can be applied to the glycoprotein
      hormone erythropoietin, an important therapeutic glycoprotein with three sites of
      N-glycosylation that are essential for in vivo biological activity. RESULTS: Wild
      type recombinant erythropoietin and three mutants in which glycosylation site
      asparagine residues had been changed to cysteines (His(10)-WThEPO, His(10)
      Asn24Cys, His(10)-Asn38Cys, His(10)-Asn83CyshEPO) were overexpressed and purified
      in yields of 13 mg l(-1) from Escherichia coli. Chemical glycosylation with
      glycosyl-beta-N-iodoacetamides could be monitored by electrospray MS. Both in the
      wild-type and in the mutant proteins, the potential side reaction of the other
      four cysteine residues (all involved in disulfide bonds) were not observed. Yield
      of glycosylation was generally about 50% and purification of glycosylated protein
      from non-glycosylated protein was readily carried out using lectin affinity
      chromatography. Dynamic light scattering analysis of the purified glycoproteins
      suggested that the glycoforms produced were monomeric and folded identically to
      the wild-type protein. CONCLUSIONS: Erythropoietin expressed in E. coli bearing
      specific Asn-->Cys mutations at natural glycosylation sites can be glycosylated
      using beta-N-glycosyl iodoacetamides even in the presence of two disulfide bonds.
      The findings provide the basis for further elaboration of the glycan structures
      and development of this general methodology for the synthesis of semi-synthetic
      glycoproteins.

PMID- 11251290
TI  - Design and utility of oligonucleotide gene probes for fungal polyketide
      synthases.
AB  - BACKGROUND: Recent advances in the molecular biology of polyketide biosynthesis
      have allowed the engineering of polyketide synthases and the biological
      ('combinatorial') synthesis of novel polyketides. Additional structural diversity
      in these compounds could be expected if more diverse polyketide synthases (PKS)
      could be utilised. Fungal polyketides are highly variable in structure,
      reflecting a potentially wide range of differences in the structure and function
      of fungal PKS complexes. Relatively few fungal synthases have been investigated,
      perhaps because of a lack of suitable genetic techniques available for the
      isolation and manipulation of gene clusters from diverse hosts. We set out to
      devise a general method for the detection of specific PKS genes from fungi.
      RESULTS: We examined sequence data from known fungal and bacterial polyketide
      synthases as well as sequence data from bacterial, fungal and vertebrate fatty
      acid synthases in order to determine regions of high sequence conservation. Using
      individual domains such as beta-ketoacylsynthases (KS), beta-ketoreductases (KR)
      and methyltransferases (MeT) we determined specific short (ca 7 amino acid)
      sequences showing high conservation for particular functional domains (e.g.
      fungal KR domains involved in producing partially reduced metabolites; fungal KS
      domains involved in the production of highly reduced metabolites etc.).
      Degenerate PCR primers were designed matching these regions of specific homology
      and the primers were used in PCR reactions with fungal genomic DNA from a number
      of known polyketide producing species. Products obtained from these reactions
      were sequenced and shown to be fragments from as-yet undiscovered PKS gene
      clusters. The fragments could be used in blotting experiments with either
      homologous or heterologous fungal genomic DNA. CONCLUSIONS: A number of sequences
      are presented which have high utility for the discovery of novel fungal PKS gene
      clusters. The sequences appear to be specific for particular types of fungal
      polyketide (i.e. non-reduced, partially reduced or highly reduced KS domains). We
      have also developed primers suitable for amplifying segments of fungal genes
      encoding polyketide C-methyltransferase domains. Genomic fragments amplified
      using these specific primer sequences can be used in blotting experiments and
      have high potential as aids for the eventual cloning of new fungal PKS gene
      clusters.

PMID- 11251289
TI  - Design and synthesis of peptides that bind alpha-bungarotoxin with high affinity.
AB  - BACKGROUND: Alpha-bungarotoxin (alpha-BTX) is a highly toxic snake venom alpha
      neurotoxin that binds to acetylcholine receptor (AChR) at the neuromuscular
      junction, and is a potent inhibitor of this receptor. We describe the design and
      synthesis of peptides that bind alpha-BTX with high affinity, and inhibit its
      interaction with AChR with an IC(50) of 2 nM. The design of these peptides was
      based on a lead peptide with an IC(50) of 3x10(-7) M, previously identified by us
      [M. Balass et al., Proc. Natl. Acad. Sci. USA 94 (1997) 6054] using a phage
      display peptide library. RESULTS: Employing nuclear magnetic resonance-derived
      structural information [T. Scherf et al., Proc. Natl. Acad. Sci. USA 94 (1997)
      6059] of the complex of alpha-BTX with the lead peptide, as well as structure
      function analysis of the ligand-binding site of AChR, a systematic residue
      replacement of the lead peptide, one position at a time, yielded 45 different 13
      mer peptides. Of these, two peptides exhibited a one order of magnitude increase
      in inhibitory potency in comparison to the lead peptide. The design of additional
      peptides, with two or three replacements, resulted in peptides that exhibited a
      further increase in inhibitory potency (IC(50) values of 2 nM), that is more than
      two orders of magnitude better than that of the original lead peptide, and better
      than that of any known peptide derived from AChR sequence. The high affinity
      peptides had a protective effect on mice against alpha-BTX lethality.
      CONCLUSIONS: Synthetic peptides with high affinity to alpha-BTX may be used as
      potential lead compounds for developing effective antidotes against alpha-BTX
      poisoning. Moreover, the procedure employed in this study may serve as a general
      approach for the design and synthesis of peptides that interact with high
      affinity with any desired biological target.

PMID- 11251291
TI  - Thermodynamic analysis of the interaction between YY1 and the AAV P5 promoter
      initiator element.
AB  - BACKGROUND: We previously determined the co-crystal structure of the zinc finger
      region of transcription factor YY1 (YY1Delta) bound to the initiator element
      (Inr) of the adenoassociated virus (AAV) P5 gene promoter [Houbaviy, H.B. et al.
      (1996) Proc. Natl. Acad. Sci. USA 93, 13577-13582]. Our structure explained both
      binding specificity and the ability of YY1 to support specific, unidirectional
      transcription initiation. RESULTS: To further understand Inr recognition by YY1,
      we analyzed the YY1Delta-Inr interaction by isothermal titration calorimetry
      (ITC) and used limited proteolysis, DNase I footprinting and missing nucleoside
      experiments to show that YY1Delta and full-length YY1 (YY1WT) have
      indistinguishable DNA binding properties. CONCLUSIONS: YY1 binding occurs at an
      equilibrium dissociation constant (K(d)) of about 1 microM, and exhibits a large
      negative heat capacity change (DeltaC(p)). We analyzed the thermodynamic behavior
      of YY1Delta in terms of buried solvent-accessible surface area resulting from
      interaction of two rigid bodies, which could not explain our measured value of
      DeltaC(p). We must, therefore, postulate conformational changes in YY1 and/or the
      Inr or question the validity of current DeltaC(p) analysis methods for protein
      DNA interactions.

PMID- 11251292
TI  - Identification of Claisen cyclase domain in fungal polyketide synthase WA, a
      naphthopyrone synthase of Aspergillus nidulans.
AB  - BACKGROUND: Based on the homology with fatty acid synthases and bacterial
      polyketide synthases (PKSs), thioesterase domains have been assigned at the C
      terminus regions of fungal iterative type I PKSs. We previously overexpressed
      Aspergillus nidulans wA PKS gene in a heterologous fungal host and identified it
      to encode a heptaketide naphthopyrone synthase. In addition, expression of C
      terminus-modified WA PKS gave heptaketide isocoumarins suggesting that the C
      terminus region of WA PKS is involved in the cyclization of the second aromatic
      ring of naphthopyrone. To unravel the actual function of the C-terminus region,
      we carried out functional analysis of WA PKS mutants by C-terminus deletion and
      site-directed mutagenesis. RESULTS: Only the 32 amino acid deletion from the C
      terminus of WA PKS caused product change to heptaketide isocoumarins from
      heptaketide naphthopyrone, YWA1 1, a product of intact WA PKS. Further C-terminus
      deletion mutant of WA PKS up to Ser(1967), an active site residue of so far
      called thioesterase, still produced isocoumarins. Site-directed mutagenesis of
      amino acid residues in this C-terminus region showed that even a single mutation
      of S1967A or H2129Q caused production of isocoumarin instead of naphthopyrone.
      Furthermore, the role of tandem acyl carrier proteins (ACPs), a typical feature
      of fungal aromatic PKSs, was examined by site-directed mutagenesis and the
      results indicated that both ACPs can function as ACP independently. CONCLUSIONS:
      Claisen-type cyclization is assumed to be involved in formation of aromatic
      compounds by some fungal type I PKSs. These PKSs have a quite identical
      architecture of active site domain organization, beta-ketoacyl synthase,
      acyltransferase, tandem ACPs and thioesterase (TE) domains. Since the C-terminus
      region of WA PKS of this type was determined to be involved in Claisen-type
      cyclization of the second ring of naphthopyrone, we propose that the so far
      called TE of these PKSs work not just as TE but as Claisen cyclase.

PMID- 11251293
TI  - A bridge between the RNA and protein worlds? Accelerating delivery of chemical
      reactivity to RNA and DNA by a specific short peptide (AAKK)(4).
AB  - BACKGROUND: RNA can catalyze diverse chemical reactions, leading to the
      hypothesis that an RNA world existed early in evolution. Today, however,
      catalysis by naturally occurring RNAs is rare and most chemical transformations
      within cells require proteins. This has led to interest in the design of small
      peptides capable of catalyzing chemical transformations. RESULTS: We demonstrate
      that a short lysine-rich peptide (AAKK)(4) can deliver a nucleophile to DNA or
      RNA and amplify the rate of chemical modification by up to 3400-fold. We also
      tested similar peptides that contain ornithine or arginine in place of lysine,
      peptides with altered stereochemistry or orientation, and peptides containing
      eight lysines but with different spacing. Surprisingly, these similar peptides
      function much less well, suggesting that specific combinations of amino acids,
      charge distribution, and stereochemistry are necessary for the rate enhancement
      by (AAKK)(4). CONCLUSIONS: By appending other reactive groups to (AAKK)(4) it
      should be possible to greatly expand the potential for small peptides to directly
      catalyze modification of DNA or RNA or to act as cofactors to promote ribozyme
      catalysis.

PMID- 11251294
TI  - Role of type II thioesterases: evidence for removal of short acyl chains produced
      by aberrant decarboxylation of chain extender units.
AB  - BACKGROUND: Modular polyketide synthases (PKSs) function as molecular assembly
      lines in which polyketide chains are assembled by successive addition of chain
      extension units. At the end of the assembly line, there is usually a covalently
      linked type I thioesterase domain (TE I), which is responsible for release of the
      completed acyl chain from its covalent link to the synthase. Additionally, some
      PKS clusters contain a second thioesterase gene (TE II) for which there is no
      established role. Disruption of the TE II genes from several PKS clusters has
      shown that the TE II plays an important role in maintaining normal levels of
      antibiotic production. It has been suggested that the TE II fulfils this role by
      removing aberrant intermediates that might otherwise block the PKS complex.
      RESULTS: We show that recombinant tylosin TE II behaves in vitro as a TE towards
      a variety of N-acetylcysteamine and p-nitrophenyl esters. The trends of
      hydrolytic activity determined by the kinetic parameter k(cat)/K(M) for the
      analogues tested indicates that simple fatty acyl chains are effective
      substrates. Analogues that modelled aberrant forms of putative tylosin
      biosynthetic intermediates were hydrolysed at low rates. CONCLUSIONS: The
      behaviour of tylosin TE II in vitro is consistent with its proposed role as an
      editing enzyme. Aberrant decarboxylation of a malonate-derived moiety attached to
      an acyl carrier protein (ACP) domain may generate an acetate, propionate or
      butyrate residue on the ACP thiol. Our results suggest that removal of such
      groups is a significant role of TE II.

PMID- 11251296
TI  - Regulation of interleukin-12 production by G-protein-coupled receptors.
AB  - G-protein-coupled receptors have long been known to play a critical role in the
      recruitment and migration of leukocytes to areas of inflammation. This review
      will focus, however, on emerging data that G-protein-coupled receptors can
      modulate cytokine production by antigen-presenting cells including interleukin-12
      and tumor necrosis factor-alpha and may therefore play a significant role in the
      regulation of innate and acquired immunity.

PMID- 11251298
TI  - TNF-alpha and IL-12: a balancing act in macrophage functioning.
AB  - Tumor necrosis factor alpha (TNF-alpha) and interleukin 12 (IL-12) are two major
      macrophage-derived mediators of inflammatory responses in mammals. Increasing
      evidence suggests that TNF-alpha is a double-edged sword with both
      proinflammatory and anti-inflammatory propensities. This article discusses the
      inter-regulation of TNF-alpha and IL-12 and the impact on the function of
      macrophages in innate and adaptive immunity.

PMID- 11251297
TI  - Complement and IL-12: yin and yang.
AB  - Interleukin 12 (IL-12) is central to the orchestration of cell-mediated immune
      responses in the innate as well as the adaptive immune system. Recent studies of
      the pathogenesis of diseases as disparate as measles and asthma have suggested
      that the complement system, itself at the interface of innate and adaptive
      immunity, is a biologically relevant regulator of IL-12 production. These data
      are reviewed here.

PMID- 11251299
TI  - Stimulatory and inhibitory signals originating from the macrophage Fcgamma
      receptors.
AB  - The macrophage receptors for the Fc portion of immunoglobulin G (FcgammaR) have
      long been known to mediate a variety of effector functions that are vital to the
      adaptive immune response. Recent studies, however, have begun to stress potential
      regulatory roles that these receptors can play in modulating immune and
      inflammatory responses. In this article we discuss the activating and inhibitory
      properties of the individual macrophage FcgammaR and the conditions under which
      these heterologous responses can occur.

PMID- 11251300
TI  - Inhibitory neuropeptide receptors on macrophages.
AB  - The immune response, both in innate and adaptive immunity, is controlled at
      several levels, including signaling from the central nervous system.
      Neuropeptides released within the lymphoid organs modulate the immune response,
      either as stimulators or inhibitors. The subject of this review is the
      description of macrophage-expressed receptors of inhibitory neuropeptides. We
      describe the inhibitory effects on macrophage function for several neuropeptides,
      the receptors that mediate those activities, and the molecular mechanisms
      initiated by some of these receptors in terms of transduction pathways and
      transcriptional factors.

PMID- 11251301
TI  - The function of scavenger receptors expressed by macrophages and their role in
      the regulation of inflammation.
AB  - Macrophages are able to recognise and internalise apoptotic and foreign cells
      from the tissue microenvironment and, where pertinent, initiate inflammation and
      macrophage activation. Regulation of this protective response is important so as
      to prevent inappropriate activation of host cells and excessive tissue damage.
      Scavenger receptors (SRs) are widely expressed by macrophages and are able to
      bind a diverse array of endogenous and foreign molecules. Studies have
      concentrated on the role of the receptors in atherosclerosis as they can
      endocytose modified lipoproteins, however, this review will detail the
      accumulating evidence that SRs function in innate immunity and macrophage control
      during inflammation.

PMID- 11251302
TI  - Pulmonary collectins and innate host defense of the lung.
AB  - Surfactant proteins A and D (SP-A and SP-D) are members of the collectin family
      of polypeptides expressed in the respiratory tract that bind bacterial, fungal
      and viral pathogens, enhancing their opsonization and killing by phagocytic
      cells. Clearance of bacterial pathogens including group B streptococci,
      Haemophilus influenza, Pseudomonas aeruginosa and viral pathogens, respiratory
      syncytial virus, adenovirus and influenza A virus, was deficient in SP-A(-/-)
      mice. SP-A deficiency was associated with enhanced inflammation and synthesis of
      proinflammatory cytokines. SP-D(-/-) mice cleared these bacteria as efficiently
      as wild-type mice; however, clearance of viral pathogens was deficient in SP-D(-/
      ) mice and associated with increased inflammation. SP-A and SP-D play critical
      and distinct roles in the regulation of alveolar macrophage function and
      inflammation, contributing to innate defense of the lung.

PMID- 11251303
TI  - Influence of TT virus on the histopathological features of nonalcoholic fatty
      liver disease.
AB  - The sera of 38 patients with nonalcoholic fatty liver disease (NAFLD) including
      nonalcoholic steatohepatitis (NASH), were tested for TT virus (TTV) DNA by
      polymerase chain reaction (PCR) using three different primer pairs (UTR PCR, N22
      PCR and genotype-1 PCR), and various histological features of the liver biopsy
      specimens were compared among those who were positive or negative for TTV
      infection. By UTR PCR which detects all TTV genotypes, TTV DNA was detected in 37
      (97%) of the 38 patients. In contrast, N22 PCR which detects primarily TTV
      genotypes 1-4, detected TTV DNA in 18 patients (47%). In the liver biopsy
      specimens, moderate to many acidophilic bodies, moderate to marked focal/spotty
      necrosis of hepatocytes and marked stellate, pericellular or perivenular fibrosis
      were observed significantly more frequently among those who were positive for TTV
      DNA by N22 PCR, than among those who were negative by N22 PCR. Twelve patients
      (32%) were positive for TTV genotype 1. Moderate to marked vacuolation of nuclei,
      moderate to many acidophilic bodies, and moderate to marked focal/spotty necrosis
      as well as marked stellate, pericellular or perivenular fibrosis were found
      significantly more frequently in the TTV genotype 1-positive group than in the
      TTV genotype 1-negative group. These results suggest that certain TTV genotypes
      including genotype 1 influence the necrosis and inflammation of hepatocytes and
      liver fibrosis in NAFLD patients.

PMID- 11251304
TI  - Changes of DNA titer and sequence variance of TT virus in hepatic disorders.
AB  - TT virus (TTV) has been reported to occur in association with elevated alanine
      aminotransferase (ALT) levels in patients with posttransfusion hepatitis of
      unknown etiology. We examined whether the presence, change of DNA titer, or
      variation in sequence of this virus is associated with acute or chronic liver
      dysfunction in Japanese. We detected TTV by polymerase chain reaction (PCR) using
      primers generated from the conserved region of the TTV genome. Direct DNA
      sequencing of the original N22 region was used to characterize TTV isolates. We
      detected TTV DNA in 15 (25%) of 60 patients with liver dysfunction. Variants
      recovered from infected patients formed four genotypes/subtypes, corresponding to
      G1a, G1b, G2, and G4. Although TTV DNA titers in patients with G2 and G4 were
      lower than those with G1, TTV was consistently detected regardless of
      genotype/subtype. TTV infection continued for at least 1 year after normalization
      of ALT level in patients with acute liver dysfunction. Changes in DNA titer,
      substitutions of deduced amino acids, and variety of quasispecies of TTV were
      detected during the observation period, but no significant fluctuation in ALT
      level was found. We conclude that persistent infection, changes in DNA titer, and
      variation in sequence of this novel virus are not significantly related to
      hepatic disorders.

PMID- 11251305
TI  - Clinical, virological, immunological, and pathological significance of GB virus
      C/hepatitis G infection in patients with chronic hepatitis C.
AB  - GB virus-C (GBV-C)/hepatitis G virus (HGV), a single-strand RNA virus, has been
      identified as a transfusion transmissible virus and categorized as a member of
      the Flaviridiae family. GBV-C/HGV superinfection in patients with chronic
      hepatitis C is not seen uncommonly, most likely because of the similar
      transmission routes. This study aimed to investigate the prevalence of GBV-C/HGV
      infection in 100 Chinese patients with histologically proven chronic hepatitis C,
      and to clarify the clinical, virological, immunological, and histopathological
      impact of GBV-C/HGV infection on chronic hepatitis C patients. Serum GBV-C/HGV
      RNA was positive in 22 (22%) of the 100 chronic hepatitis C patients. There were
      no significant differences in mean age, gender, and serum liver biochemical tests
      between GBV-C/HGV infected and non-infected chronic hepatitis C patients. The HCV
      genotype distribution and mean serum HCV RNA level were not significantly
      different between patients with and without GBV-C/HGV co-infection. The presence
      of serum autoantibodies (anti-nuclear antibody and anti-smooth muscle antibody)
      and cryoglobulinemia showed no significant difference between the two groups.
      Liver histopathological analysis revealed no significant difference in the grade
      of periportal, portal, and intralobular necro-inflammation, in the stage of
      fibrosis/cirrhosis, or in the presence of steatosis and lymphoid
      aggregation/follicle formation between patients with and without GBV-C/HGV
      infection. However, a higher degree of bile duct damage was noted in chronic
      hepatitis C patients co-infected with GBV-C/HGV infection than in those without
      infection (P=0.036). In conclusion, GBV-C/HGV infection had no apparent influence
      on the clinical, immunological, or virologic features of patients with chronic
      hepatitis C. However, the clinical significance of a higher degree of bile duct
      damage in patients with HCV and GBV-C/HGV co-infection deserves further
      investigation.

PMID- 11251306
TI  - Fecal shedding of hepatitis A virus in Indian patients with hepatitis A and in
      experimentally infected Rhesus monkey.
AB  - Hepatitis A is highly endemic in India. The surveillance reports for the disease
      from this region are primarily based on the demonstration of hepatitis A virus
      (HAV) specific serum IgM and IgG antibodies. The present study was conducted to
      assess the presence and duration of fecal shedding of HAV in patients with
      hepatitis A and in an experimentally infected rhesus monkey. Nested reverse
      transcription polymerase chain reaction (RT-PCR) was applied to fecal specimens
      from 67 sporadic cases of hepatitis A. Recent infection with HAV in these cases
      was evidenced by the presence of serum anti-HAV IgM. Fecal HAV RNA positivity was
      observed in nearly 40% patients. The proportion of HAV RNA positivity in fecal
      specimens obtained within the first week (36.58%) was not different from those
      collected in 2-12 weeks post onset (42.42%) (P>0.05). A significant number of HAV
      RNA positive stool specimens showed presence of full virus particles by immune
      electron microscopy (IEM). Extended fecal shedding of HAV could be a major
      contributory factor for high circulation of virus thereby maintaining
      hyperendemicity of the disease. One of the IEM positive samples was inoculated
      into an anti-HAV negative rhesus monkey. Serum alanine amino transferase levels
      of the monkey remained within the normal limits. However, HAV RNA positivity in
      the feces was noted from 3 to 50 days post inoculation. The monkey seroconverted
      to anti-HAV IgM on day 31. This study records prolonged excretion of HAV in
      humans as well as in experimentally infected rhesus monkey.

PMID- 11251307
TI  - Prevalence of hepatitis viruses among multi-transfused homogenous thalassaemia
      patients.
AB  - Thalassaemic children being multi-transfused are at increased risk of
      parenterally transmissible hepatitis viruses and majority of them prone to
      develop chronic liver disease. The study is designed to find out the prevalence
      of hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV)
      seromarkers and correlation of age, sex, number of transfusions and the viral
      aetiology in thalassaemics of central India. One hundred and four thalassaemic
      children were subjected to clinical, biochemical and serological analysis for the
      HBV, HCV and HDV viruses. The chi(2) test was applied to check the statistical
      significance of different variables. In the present study HBV markers were
      detected in 57 (56%) of the subjects while anti-HCV antibodies were observed in
      21% of the patients. However, only four subjects were detected hepatitis B
      surface antigen (HBsAg) reactive but none of them were reactive for anti-HDV
      antibodies. Forty patients had raised alanine transaminase (ALT) levels and among
      them two were HBsAg reactive, 16 were anti-HBc antibody positive and 14 were anti
      HCV reactive. The prevalence of hepatitis viruses and raised ALT levels are found
      to be significantly associated with the increasing age and number of blood units
      transfused to them. The present findings also document the excellent contribution
      of stringent screening of blood units and HBV vaccination programme for
      containing the HBV infection among thalassaemics.

PMID- 11251308
TI  - Serum levels of HCV RNA and core protein before and after incubation at 37
      degrees C for 24 h.
AB  - The kinetics of HCV during interferon (IFN) therapy have recently been described
      and the estimated virion half-life is an average of 2.7 h, suggesting that HCV
      infection is highly dynamic. The aim of this study was to evaluate serum levels
      of HCV-RNA and HCV core protein (HCV-Ag) before and after incubation at 37
      degrees C for 24 h. We also evaluated the viral kinetics during IFN treatment by
      determining their serum levels at 0, 24 and 48 h, and day 8 after the start of
      treatment. The decay slope was calculated as the logarithm of the ratio of HCV
      RNA levels at 0 and 24 h of incubation: log(virus load) 24 h-log(virus load) 0 h
      and the estimated half-life was also calculated. The decay slope was -1.66+/-0.75
      (-4.12 to -0.18) (mean+/-S.D. (range)) and the estimated virion half-life was
      6.2+/-6.9 h (1.8-39.3). The HCV-RNA level was rapidly decreased to 6.8+/-13.1% of
      the initial load after incubation independently of the serotype. In contrast, the
      HCV-Ag level after incubation for 24 h was 98.7+/-12.2% of the initial level. The
      synthesized naked HCV-RNA (equivalent to 10(7) copy/ml) was not detected after 1
      min incubation. These data suggested that HCV virions are very unstable and
      collapsed rapidly and that HCV-RNA, existing outside of virions, is immediately
      degraded in serum, whereas HCV-Ag remains stable. IFN treatment caused a rapid
      decrease in the levels of both HCV-RNA and HCV-Ag. The HCV-RNA decay slope was 
      1.95+/-0.96 (range: -3.48 to -0.50) and was similar to that seen in the
      incubation study. Our result suggested the significance of measuring HCV-Ag
      during clinical management independently of HCV-RNA, especially because of its
      high stability.

PMID- 11251309
TI  - Synchronized disappearance of serum HCV-RNA, anti-U1 RNP, anti-La/SS-B, and anti
      Scl-70 in a patient with chronic hepatitis.
AB  - The authors report a rare case of chronic hepatitis in whom normalization of
      serum aminotransferases was associated with disappearance of serum hepatitic C
      virus (HCV)-ribonucleic acid (RNA), anti-U1 RNP, anti-La/SS-B, and anti-Scl-70
      antibodies without treatment of interferon or corticosteroids. A 27-year-old
      Japanese woman was diagnosed with chronic hepatitis C, with positive anti-nuclear
      antibody, anti-U1 RNP, anti-La/SS-B, and anti-Scl-70 antibodies. Histopathologic
      examination of a liver biopsy specimen showed a periportal interface hepatitis
      with a predominantly lymphoplasmacytic necroinflammatory infiltrate and lobular
      hepatitis. After two-year treatment with ursodeoxycholic acid (UDCA), serum
      aminotransferases normalized and serum HCV-RNA, anti-U1 RNP, anti-La/SS-B, and
      anti-Scl-70 antibodies disappeared. It was unclear whether disappearance of HCV
      RNA was spontaneous, due to some immunomodulating effects of UDCA, or other
      unknown mechanism, but host immune response may be associated with HCV
      elimination.

PMID- 11251310
TI  - Prevention of hepatitis C virus infection in a chimpanzee by vaccination and
      epitope mapping of antiserum directed against hypervariable region 1.
AB  - We previously reported on a chimpanzee immunized with both putative envelope
      glycoproteins (E1 and E2) of hepatitis C virus (HCV), strain HCV-N2, and
      synthetic peptides of hypervariable region 1 (HVR1) of a different isolate, HCV
      #6. The chimpanzee showed complete protection against HCV-#6 infection only when
      the titer of anti-HVR1 increased, suggesting that an immune response to the HVR1
      is more essential in protecting a chimpanzee from HCV infection than an immune
      response to E1 and E2. In this study, we immunized this chimpanzee with only
      synthetic HVR1 peptides after anti-E1 and anti-E2 antibody levels dropped and
      then rechallenged with 10 infectious chimpanzee doses of HCV. The immunized
      animal was protected, and neutralization of HCV with the antiserum from the
      protected animal was achieved by inoculating another chimpanzee with HCV
      preneutralized by this antiserum mixture. Epitope analysis of HVR1 by Pin-ELISA
      using this antiserum seemed to demonstrate that the antibody response was
      directed mainly against the C terminus of HVR1. Moreover, our results showed
      that, if a part of the sequences was conserved, a broad cross-reactivity of the
      antiserum could be observed, even if amino-acid sequences in this epitope were
      substituted for those of other HCV strains.

PMID- 11251311
TI  - An open-label trial of consensus interferon 15 ug in the treatment of Chinese
      patients with chronic hepatitis C.
AB  - Consensus interferon (CIFN), a novel recombinant type 1 interferon (IFN), has
      been used recently to treat patients with chronic hepatitis C virus (HCV)
      infection. CIFN 9 ug, given subcutaneously 3 times a week for 24 weeks, offers
      sustained biochemical and virological responses in 32% of Chinese patients
      studied in Taiwan. Whether a higher dosage of CIFN will have greater efficacy is
      of clinical interest. This open-label trial was conducted to determine the
      efficacy and safety of CIFN 15 ug, given subcutaneously 3 times a week for 24
      weeks, in 35 Chinese patients with chronic hepatitis C who in a previous
      randomized, controlled CIFN trial received placebo (n=16) or showed no sustained
      response to CIFN 3 ug (n=14) or 9 ug (n=5), 3 times a week for 24 weeks. Efficacy
      was assessed by normalization of serum alanine transaminase (ALT) levels and
      clearance of serum HCV RNA to undetectable levels as measured by reverse
      transcription polymerase chain reaction (RT-PCR). Results showed 14 of 35
      patients (40%) achieved normalized serum ALT and cleared serum HCV RNA at the end
      of treatment, and 11 patients (31%) maintained a sustained response 24 weeks
      after treatment was discontinued. The sustained response rate was 31% in patients
      who had received a placebo injection in the previous trial, 36% in patients who
      had relapsed or not responded to previous CIFN 3 ug treatment, and 20% in
      patients who had relapsed or not responded to previous CIFN 9 ug treatment
      (P>0.05). Upon re-treatment with CIFN 15 ug, sustained response was achieved in
      two of three patients who had relapsed from previous CIFN 3 ug treatment and in
      one of three patients who had relapsed from previous CIFN 9 ug treatment. CIFN 15
      ug re-treatment achieved a sustained response in three of eleven patients and in
      none of two patients who were non-responders from previous CIFN 3 ug or CIFN 9 ug
      treatments respectively. Patients tolerated the treatment well, but two patients
      withdrew from the study due to intolerable side effects. In conclusion,
      subcutaneous injection of CIFN 15 ug, 3 times a week for 24 weeks, showed a
      similar efficacy as CIFN 9 ug 3 times a week treatment in Chinese patients with
      chronic hepatitis C. The treatment may benefit patients who have relapsed from a
      previous 3 ug or 9 ug treatment.

PMID- 11251312
TI  - Expression of Nov, CYR61 and CTGF genes in human hepatocellular carcinoma.
AB  - CCN family genes, Nov, CYR61 and CTGF, are immediate-early genes expressed in
      fibroblasts following growth stimuli. Aberrant expression of Nov has been found
      in human Wilms' tumor, and suggested to be involved in tumorigenesis. The aim of
      our experiments is to examine the expression of CCN family genes in human
      hepatocellular carcinomas (HCCs) and find the correlation of these gene
      expressions with clinicopathological parameters. A pair of tumor and surrounding
      non-tumor tissues were obtained from 23 patients with HCC and six with metastatic
      liver tumor. Total cellular RNA isolated from tissues was analyzed for the
      presence of mRNA of CCN family genes by the reverse-transcription polymerase
      chain reaction. Nov, CYR61 and CTGF mRNA were identified in 17 (73.9%), 17
      (73.9%), six (26.1%) tumors, and in nine (39.1%), 16 (69.6%), one (4.3%)
      surrounding non-tumor tissues of 23 patients with HCC. No significant difference
      was found in clinicopathological parameters between cases with HCC negative and
      positive for these gene expressions. The prevalence of Nov and CTGF expression in
      HCC is significantly higher than those in surrounding non-tumor. The same
      tendency was found in metastatic tumors. These results suggest that Nov and CTGF
      is associated with the development of tumors in the liver.

PMID- 11251313
TI  - Chronic alcohol exposure of rats exacerbates apoptosis in hepatocytes and
      sinusoidal endothelial cells.
AB  - Background/aims: The liver apoptotic response to chronic alcohol consumption
      remains poorly characterized. The purpose of this study was to determine in rats
      the effects of chronic alcohol consumption on the relative magnitude of apoptosis
      in two major targets of alcohol-induced liver injury: the hepatocyte (Hep) and
      sinusoidal endothelial cell (SEC). Methods: Rats were fed a liquid diet
      containing either alcohol or isocaloric amounts of maltose-dextrin for 14 weeks.
      Hep and SEC were isolated by liver perfusion with collagenase followed by
      centrifugal elutriation. The state of the liver was assessed on the basis of
      light microscopic appearance, plasma liver enzymes (alanine and aspartate:2
      oxoglutarate amino transferases), and the content of malondialdehyde in Hep.
      Apoptosis was assessed on the basis of DNA fragmentation in the whole organ
      (TUNEL), and caspase-3 and -8 activity in isolated cells. A mechanistic approach
      was also undertaken by measuring mRNA expression and the amount of protein for
      Fas/CD95, Fas ligand, caspase-3, Bax, Bcl-X(L), and Bcl-2 in the isolated Hep and
      SEC. Results: The livers of alcohol-fed rats displayed prominent steatosis.
      Oxidative stress was also present as reflected by an increase in the
      malondialdehyde content of Hep. Alcohol consumption increased apoptosis in the
      whole liver assessed on the basis of TUNEL procedure and in Hep and SEC as
      reflected by significant increase in caspase-3 activity. Of the multiple pro- and
      anti-apoptotic factors determined in this study, significant changes as assessed
      by both mRNA expression and the amount of proteins, were observed only in the SEC
      compartment. Conclusions: The data presented in this study indicate that: (1)
      chronic alcohol consumption in rats leads to a moderate augmentation of apoptosis
      in the whole liver and in two liver cell types which are targets for injury in
      alcoholic liver disease: Hep and SEC; (2) the mechanisms recruited/activated by
      these two types of liver cells to initiate and execute apoptosis in response to
      alcohol vary with the cell type.

PMID- 11251314
TI  - The effect of nitric oxide production by sinusoidal endothelial cells on
      preservation injury during cold ischemia.
AB  - Multifactorial elements are responsible for preservation and reperfusion injury
      in liver allografts. Sinusoidal endothelial cells (SECs) are a primary target of
      cold preservation injury of the liver. We examined the correlation between nitric
      oxide (NO) production by SECs and their injury during cold preservation. SECs
      were isolated from rat livers and preserved in either Euro-Collins (EC) or
      University of Wisconsin (UW) solution. Injury to the SECs was more severe when
      preserved in the EC solution than in the UW solution during cold ischemia. In
      addition, NO production by SECs was found to be proportionate to the cell injury.
      Cell viability was not improved by the addition of NO inhibitor, L-NMMA. Further,
      NO inhibitor was detrimental to the SECs in a 24-h preservation in UW solution.
      LDH release by SECs preserved in UW solution supplemented with L-NMMA was 11.10+/
      2.03 IU/l, while that in UW solution alone was 3.70+/-0.70 IU/l (P<0.01).
      Together, our results suggest that NO protects SECs during cold preservation and
      that NO from SECs may have beneficial effects on the liver during cold ischemia.

PMID- 11251315
TI  - Competition of pravastatin and dibromosulfophthalein on the electroneutral and
      electrogenic tetrabromosulfophthalein uptake in rat liver.
AB  - The effect of pravastatin (PVST) and dibromosulfophthalein (DBSP) on the hepatic
      uptake of bromosulfophthalein (BSP) was investigated in liver plasma membrane
      vesicles enriched on basolateral fraction. BSP uptake was measured either in the
      absence (electroneutral component) or in the presence of a membrane potential
      (electrogenic component). PVST and DBSP inhibited both components of BSP uptake.
      The Dixon and Cornish-Bowden plot of the data revealed a competitive type of
      inhibition for PVST and DBSP on the electroneutral portion of BSP uptake. The
      inhibition constants (K(i), mM) were 0.650+/-0.050 for PVST and 0.020+/-0.005 for
      DBSP. These data indicate that PVST, DBSP and BSP share a common electroneutral
      transport system at basolateral liver plasma membrane. On the contrary, PVST
      exerted a non-competitive type of inhibition on the electrogenic component of BSP
      uptake (K(i)=0.210+/-0.040 mM) and DBSP produced a mixed type of inhibition
      (K(i)=0.018+/-0.002 mM). These results indicate that PVST does not compete with
      the electrogenic BSP carrier system at the level of the substrate binding site
      but modulates its functionality and that DBSP shares the electrogenic component
      of BSP transport and also modulates the performance of this carrier system.

PMID- 11251316
TI  - Mammal-like striatal functions in Anolis. I. Distribution of serotonin receptor
      subtypes, and absence of striosome and matrix organization.
AB  - Serotonin (5-HT) 5-HT(2A) and 5-HT(2C) receptors are thought to play important
      roles in the mammalian striatum. As basal ganglia functions in general are
      thought highly conserved among amniotes, we decided to use in situ
      autoradiographic methods to determine the occurrence and distribution of
      pharmacologically mammal-like 5-HT(2A) and 5-HT(2C) receptors in the lizard,
      Anolis carolinensis, with particular attention to the striatum. We also
      determined the distributions of 5-HT(1A), 5-HT(1B/D), 5 HT(3), and 5-HT(uptake)
      receptors for comparison. All 5-HT receptors examined showed pharmacological
      binding specificity, and forebrain binding density distributions that resembled
      those reported for mammals. Anolis 5 HT(2A/C) and 5-HT(1A) site distributions
      were similar in both in vivo and ex vivo binding experiments. 5-HT(2A & C)
      receptors occur in both high and low affinity states, the former having
      preferential affinity for (125)I-(+/-)-2,5-dimethoxy-4-iodo-amphetamine
      hydrochloride ((125)I-DOI). In mammals (125)I-DOI binding shows a patchy density
      distribution in the striatum, being more dense in striosomes than in surrounding
      matrix. There was no evidence of any such patchy density of (125)I-DOI binding in
      the anole striatum, however. As a further indication that anoles do not possess a
      striosome and matrix striatal organization, neither (3)H-naloxone binding nor
      histochemical staining for acetylcholinesterase activity (AChE) were patchy. AChE
      did show a band-like striatal distribution, however, similar to that seen in
      birds.

PMID- 11251317
TI  - Mammal-like striatal functions in Anolis. II. Distribution of dopamine D(1) and
      D(2) receptors, and a laminar pattern of basal ganglia sub-systems.
AB  - We used in situ autoradiographic ligand binding methods to determine the
      occurrence and distribution of dopamine D(1) and D(2) receptor sub-types in the
      anole lizard, Anolis carolinensis. Both were present and exhibited
      pharmacological specificity characteristics similar to those described for
      mammals. However, unlike in mammals where in the neostriatum [outside the nucleus
      accumbens/olfactory tubercle complex (NA/OT)] these receptors exhibit only slight
      dorsolateral (D(2) high, D(1) low) to ventromedial (D(1 )high, D(2) low)
      gradients that co mingle extensively, in the anole striatum outside the NA/OT
      there was a striking laminar pattern, with little if any overlap between D(2)
      (high in a dorsal band) and D(1) (high ventral to the D(2) band) distributions.
      As D(1) receptors are related to the direct and D(2) to the indirect basal
      ganglia (BG) subsystems in mammals, we also determined anole striatal
      distributions of pre-proenkephalin mRNA, a marker for striatal efferents to the
      indirect BG subsystem in mammals. Here, too, there was a striking laminar
      pattern, with pre-proenkephalin mRNA in a band similar to that seen for D(2)
      receptors. The crisp neuroanatomical separation between these classic BG
      subsystem markers in Anolis striatum make this species attractive for the study
      of such systems' functions during behavior.

PMID- 11251318
TI  - Differential stress coping in wild and domesticated sea trout.
AB  - Offspring of wild and sea-ranched (domesticated) sea trout (Salmo trutta)
      originating from the same river, were reared under identical hatchery conditions
      from the time of fertilization. At one year of age individual fish were exposed
      to two standardized stressors; transfer to a novel environment, with or without a
      simultaneous predator exposure. Blood plasma concentrations of glucose and
      cortisol were analyzed along with brain levels of dopamine (DA), 3,4
      hydroxyphenylacetic acid (DOPAC, a major DA metabolite), serotonin (5
      hydroxytryptamine, 5-HT), and 5-hydroxyindoleacetic acid (5 HIAA, a major 5-HT
      metabolite). Transfer to a novel environment, alone as well as in combination
      with predator exposure, resulted in elevated plasma concentrations of glucose and
      cortisol. Moreover, exposure to these stressors resulted in elevated brain levels
      of 5-HT and 5-HIAA, as well as elevated brain 5-HIAA/5-HT and DOPAC/DA ratios.
      Wild trout displayed significantly higher post stress plasma glucose levels than
      domesticated fish. Similarly, following stress, brain 5-HIAA/5-HT and DOPAC/DA
      ratios were significantly higher in wild than in domesticated fish. These
      differences were not caused by differences in brain levels of 5-HIAA and DOPAC,
      but instead by differences in brain 5-HT and DA concentrations. These results
      suggest that domestication results in attenuated stress responses in trout, and
      that alterations in brain monoamine neurotransmission are part of this effect.

PMID- 11251319
TI  - Sexually dimorphic expression of glutamate decarboxylase mRNA in the hypothalamus
      of the deep sea armed grenadier, Coryphaenoides (Nematonurus) armatus.
AB  - Glutamate decarboxylase (GAD), is a key enzyme in the central nervous system
      (CNS) that synthesizes the inhibitory neurotransmitter gamma-aminobutyric acid
      (GABA) from glutamate. Our previous phylogenetic studies on the evolution of this
      enzyme indicates that there are at least two distinct forms: GAD65 and GAD67.
      They are the products of separate genes and probably derive from a common
      ancestral GAD gene following gene duplication prior to the emergence of the
      teleosts more than 200 Myr ago. Furthermore, a third GAD-like molecule, GAD3,
      discovered in the armed grenadier, Coryphaenoides (Nematonurus) armatus, is
      equally divergent from both GAD65 and GAD67. Specimens of C. (N.) armatus were
      collected by trawl at a depth of 4,000 m in the Porcupine Seabight (Northeastern
      Atlantic), and brains dissected and frozen for RNA extraction. All three GAD
      forms are found in the cerebellum, telencephalon and hypothalamus.
      Semiquantitative PCR analysis showed that males and females have similar levels
      of expression of GAD67 and GAD3 in the tissues studied. Independent of the sex
      examined, the levels of expression of GAD65 and GAD67 in the cerebellum were
      approximately half that in the telencephalon. GAD3 levels were approximately 30%
      higher in the cerebellum than in either the telencephalon or hypothalamus. In
      contrast to GAD67 and GAD3, hypothalamic expression of GAD65 mRNA is 1.8 times
      higher (p < 0.05) in males than in females. These data indicate that the
      expression of GAD65, a key enzyme for the synthesis of GABA is sexually dimorphic
      in females and males of C. (N.) armatus.

PMID- 11251320
TI  - Conservation of absolute foveal area in New World monkeys. A constraint on eye
      size and conformation.
AB  - The foveal specializations of five New World monkeys, the marmoset, Callithrix
      jacchus; the golden-handed tamarin, Saguinus midas niger; the squirrel monkey,
      Saimiri ustius; the capuchin monkey, Cebus apella; and the howler monkey,
      Alouatta caraya were compared. Although retinal area varies by over a factor of
      two in these monkeys, the area of the fovea does not covary with retinal area and
      remains approximately the same absolute size, as measured by the dimensions of
      the high density region of cones, or the rod-free region. This constancy in
      foveal size also holds for rhesus monkeys and humans, bringing the variation in
      retinal area to a factor of five. Alouatta caraya is unusual, distinguished by a
      very high central cone density and a small rod-free zone. Physiological
      constraints that might limit foveal area over a wide range of eye sizes are
      considered.

PMID- 11251321
TI  - Modulatory effects of the nucleus of the basal optic root on rotundal neurons in
      pigeons.
AB  - The present paper reports for the first time in birds the modulatory effects of
      the nucleus of the basal optic root (nBOR) on visual neurons in the nucleus
      rotundus in particular and those of the accessory optic system on the tectofugal
      pathway in general. Pharmacological blockade of the nBOR by lidocaine led to a
      decrease or increase in visual responsiveness of rotundal cells, suggesting
      excitatory or inhibitory actions of the nBOR on rotundal cells. These results
      were confirmed by changes in the excitability of rotundal cells following
      electrical stimulation of the nBOR. Response latency measurements implied that
      there might be at least two pathways from the nBOR to the nucleus rotundus, one
      being a direct excitatory pathway and the other an indirect inhibitory pathway
      possibly mediated by the subpretectal nucleus and the interstitio-pretecto
      subpretectal nucleus, which have been thought to send inhibitory afferents to the
      nucleus rotundus. Taken together with previous neuroanatomical and
      immunocytochemical studies, it is suggested that modulatory interactions might
      exist between the nBOR and the nRt in particular and between the accessory optic
      system and the tectofugal pathway in general in birds.

PMID- 11251330
TI  - A chronopharmacodynamic study on standard heparin, a low molecular weight heparin
      (nadroparin) and danaproid: establishing and comparing the daily variations of
      these drugs in rats.
AB  - The effects of dosing time on the anticoagulant activity of unfractionated
      heparin, low molecular weight heparin (nadroparin) and danaproid were
      investigated. The chronopharmacological comparisons of the drugs were done on the
      anti-Xa, anti-IIa activities and activated partial thromboplastin time assays.
      Several dosing times were considered and an analysis based on a population
      approach was adopted. Under unfractionated heparin, the pharmacological
      activities did not exhibit significant daily variations. In contrast, significant
      daily profiles were observed in all the biological assays performed with low
      molecular weight heparin. Anti-Xa and anti-IIa activities showed some
      fluctuations over a 24-hour period with a peak at noon. As for the variations of
      the activated partial thromboplastin time, two peaks were noted early in the
      morning and at the beginning of nightfall. As for danaproid, only a daytime
      maximum of anti-Xa activity could be found.

PMID- 11251329
TI  - Intestinal absorption of low molecular weight heparin in animals and human
      subjects.
AB  - INTRODUCTION: We had previously shown that the use of bile salts, which act as
      surfactants, facilitates the intestinal absorption of large molecules such as
      those of heparin and insulin. However, the bioavailability of unfractionated
      heparin (UFH) administered through the large intestine was low. The aim of the
      present study was to evaluate the absorption of low molecular weight heparin
      (LMWH) combined with bile salts through the gut mucosa in animals and human
      subjects. MATERIALS AND METHODS: LMWH (Fragmin, Kabi-Pharmacia, Stockholm) or UFH
      with or without sodium cholate (Sch) was administrated rectally in rats and
      healthy volunteers via a microenema. Absorption was estimated by the activated
      partial thromboplastin time (aPTT), the plasma anti-factor Xa activity and the
      plasma lipoprotein lipase (LPL) activation. RESULTS: In groups of 6 rats, LMWH at
      doses of 100--1,000 U with sodium cholate (10--20 mg/ml) was readily absorbed
      through the gut mucosa, as indicated by both, anti-factor Xa levels of up to 1
      U/ml and a dose-dependent activation of LPL. The absorption was significantly
      superior to that of UFH with Sch or LMWH given without Sch (p < 0.001). The
      plasma anti-factor Xa levels in the 6 healthy volunteers who received a
      microenema containing 25,000 U of LMWH with 20 mg/ml of Sch were 0.38 U/ml at 15
      min and 0.1 U/ml at 240 min. LPL activation and aPTT prolongation were also
      observed in these subjects. The plasma LMWH levels after rectal application were
      in the same range as those obtained after subcutaneous administration, however
      the elimination time (t 1/2) was shorter. There were no adverse reactions.
      CONCLUSIONS: Intestinal absorption of LMWH facilitated by Sch is both feasible
      and safe. A slow release formulation will be needed to prolong the plasma half
      life.

PMID- 11251331
TI  - Absence of transplacental passage of the low molecular weight heparin enoxaparin.
AB  - BACKGROUND: Venous thromboembolism (VTE) during pregnancy and puerperium remains
      a major cause of maternal morbidity and mortality. The use of low molecular
      weight heparin (LMWH) constitutes a promising alternative for the prevention of
      VTE instead of unfractionated heparin as it can be administered subcutaneously
      once daily and without coagulation measurement. Unfortunately, the safety of
      LMWHs administration for the mother and fetus has not been well established.
      STUDY DESIGN: In order to examine the safety of enoxaparin to the fetus, 24 women
      were recruited and 40 mg of enoxaparin was administered in 14 of them. All 24
      women were going to have an early termination of pregnancy due to major fetal
      malformations. Maternal blood samples were drawn before and after the injection
      of enoxaparin, while fetal blood samples were taken only after the drug
      administration. Anti-IIa and anti-Xa activities were measured. RESULTS: A
      statistically significant increase of anti-Xa activity in the mothers studied was
      pointed out, while there was no detection of anti-IIa and anti-Xa activities in
      the fetuses. CONCLUSIONS: Since no anti-IIa and anti-Xa activities were detected
      in the fetuses' blood samples, it is concluded that enoxaparin does not cross the
      placenta and therefore appears safe for the fetus.

PMID- 11251332
TI  - Characteristics of heparin-induced platelet aggregates in chronic hemodialysis
      with long-term heparin use.
AB  - This study investigated the usefulness of a new platelet aggregometer with a
      laser-scattering method for detection of heparin-induced small platelet
      aggregates in chronic hemodialysis patients. Using this device, small platelet
      aggregates (particle size 9--25 microm) were detectable, but these aggregates
      could not be detected using a conventional light transmittance aggregometer. The
      laser-scattering intensity of the small aggregates was increased with an
      increasing dosage of heparin as agonist. These aggregates were disaggregated by
      heparin neutralization with protamine sulfate. Induction of small platelet
      aggregates by heparin was inhibited by preincubation with nafamostat mesilate, a
      synthetic protease inhibitor, and cilostazol, a platelet phosphodiesterase
      inhibitor, but not by the therapeutic doses of aspirin or argatroban, a selective
      thrombin inhibitor. The dialysis patients with long-term heparin use could be
      divided into two groups: responders to heparin, who formed small aggregates with
      a scattering intensity over 0.51 x 10(5) V after addition of 0.5 IU/ml of heparin
      obtained from normal platelet-rich plasma without inductor, and nonresponders,
      who showed an intensity under 0.51 x 10(5) V. The rate of heparin responders
      among dialysis patients was significantly higher than the rate among normal
      subjects. Heparin-induced small aggregates were detected in 13 (36.1%) of 36
      normal subjects with no history of heparin infusion and in 37 (62.7%) of 59
      dialysis patients who received heparin anticoagulation during each dialysis
      session. Dialysis patients with coronary heart disease did not have a
      significantly higher rate of heparin responders than patients without
      complications. There was no significant difference in the positivity rate between
      cases complicated by diabetes and those without diabetes. In patients who had
      more than 2 episodes of thrombotic occlusions of an arteriovenous fistula, the
      rate of responders and the enhancement of scattering intensity of small
      aggregates by heparin were significantly increased compared with these in
      patients without occlusions during the preceding 2 years. Moreover, dialysis
      patients with a positive heparin response showed a marked increase in scattering
      intensity of small aggregates after heparin infusion in each dialysis session.
      Determination of the response to heparin prior to heparin use in dialysis
      patients with repeated thromboembolic complication may be useful in choosing
      anticoagulant regimens.

PMID- 11251333
TI  - Why is the standardization of prothrombin time a problem?
AB  - The standardization of prothrombin time (PT) has been a problem for more than 50
      years; by applying the methods to the same clinical material the analysis may
      explain why. The initial standardization by 2--3 times normal clotting time by
      Quick's PT assay did not standardize presently used PT assays. The ratio method
      accepted by the WHO in 1977 was not satisfactory because the intercept was
      neglected. The revised ratio method (WHO 1983) recommended calibration between
      log clotting times of normal and abnormal plasmas and a simplified conversion
      into ratios. However, by including a high proportion of normal plasmas (up to 1/3
      of abnormal) an erroneous calibration material was introduced; the conversion
      from clotting times into ratios was also more complex than predicted. The
      international sensitivity index, which is based on the simplified method,
      produced international normalized ratios (INR) that were not more standardized
      than not corrected ratios. Not corrected coagulation activities showed poor
      standardization due to the different sensitivity of assays for the protein
      induced by vitamin K absence (Pivka) inhibitor. The corresponding therapeutic
      ranges of INR and coagulation activities covered 70 and 10--20% of their scales,
      respectively. Standardization by Pivka-corrected coagulation activities against
      an international reference assay may be the preferable method.

PMID- 11251334
TI  - Factor VIII inhibitors in two families with mild haemophilia A: structural
      analysis of the mutations.
AB  - The development of inhibitory antibodies against coagulation factor VIII (FVIII)
      in patients with mild haemophilia A is uncommon. We describe here two families in
      which three or two members have developed inhibitors, suggesting a familial
      predisposition. The mutations found, in the A2 (Arg593Cys) and C1 domains
      (Tyr2105Cys), have been reported to give rise to inhibitor development in single
      individuals in addition to the family cluster we describe, strongly suggesting
      that these amino acid substitutions give rise to a more immunogenic protein. The
      analysis of structural models of activated factor VIII revealed that Arg593 is
      solvent-exposed and involved in a network of electrostatic interactions while
      Tyr2105 is partially buried and has hydrophobic interactions essentially with
      Ile2144. All these residues are strictly conserved in the FVIII amino acid
      sequence from man, pig and mouse, suggesting, at least, that they have structural
      roles. We propose that the two mutations in these families could cause mild
      haemophilia A because they induce local conformational changes (and possible
      secretion or intermolecular interaction problems, e.g., with von Willebrand
      factor) compatible with immunogenicity and production of inhibitors against the
      infused wild-type FVIII.

PMID- 11251335
TI  - Genetic heterogeneity in hereditary thrombophilia.
AB  - Venous thromboembolism is a multifactorial disease that depends on variable
      combinations of acquired and genetic risk factors. The genetic risk factors
      include loss-of-function mutations in the genes that encode proteins with clot
      restraining function, and gain-of-function mutations in procoagulant factors. The
      loss-of-function mutations are heterogeneous and comprise any mutation that
      impairs gene function. On the whole, these mutations are rare, with fewer than
      1/200--500 individuals affected. This low prevalence in the population is
      probably caused by the loss of mutant alleles from the gene pool through
      critically ill homozygous subjects. The gain-of-function mutations in
      procoagulant proteins differ from the loss-of-function mutations in at least
      three important respects: these are more homogeneous (factor V Leiden and PT
      20210), homozygous individuals are relatively mildly affected, and these are
      relatively prevalent (3--15%) in Caucasian populations.

PMID- 11251336
TI  - Aspects of the clinical management of hereditary thrombophilia: a personal
      perspective.
AB  - There is a paucity of evidence-based medicine regarding the clinical management
      of patients with inherited thrombophilia, and randomized controlled multinational
      clinical trials of anticoagulant prophylaxis, particularly of secondary
      prophylaxis, in this population are urgently required. For acute episodes of
      venous thromboembolism, no data suggest that patients with thrombophilia should
      be treated differently to those without thrombophilia. Based on the results of a
      retrospective study, it is recommended that all thrombophilic individuals receive
      short-term thromboprophylaxis with unfractionated heparin or low-molecular-weight
      heparin when they are to be exposed to circumstantial risk factors (e.g. surgery,
      prolonged immobilization, pregnancy and puerperium). In the absence of
      specifically designed clinical trials, secondary prophylaxis should be based on
      common sense and clinical experience. From this standpoint, it is recommended
      that low-risk patients be treated with oral anticoagulants for 6 months, whereas
      high-risk patients should receive lifelong anticoagulant therapy. Which treatment
      strategy to adopt for intermediate-risk patients is more controversial --
      prolongation of oral anticoagulant therapy to at least 12 months is suggested.

PMID- 11251337
TI  - Antiphospholipid syndrome: state of the art with emphasis on laboratory
      evaluation.
AB  - Antiphospholipid antibodies (aPLs) are associated with arterial and venous
      thrombosis, recurrent pregnancy loss and thrombocytopenia. Although aPLs have not
      yet been conclusively shown to be causal in thrombosis and miscarriage, they are
      useful laboratory markers for the antiphospholipid syndrome (APS). The syndrome
      can complicate another autoimmune disease, most commonly systemic lupus
      erythematosus, but more often occurs alone -- primary APS. Identification of the
      syndrome is clinically important because of the risk of recurrent thrombosis and
      the need for antithrombotic therapy in many cases. Diagnosis and treatment of APS
      represent significant challenges, however, owing to the protean clinical
      manifestations and associations, limitations of currently available laboratory
      tests for aPLs, and the lack of clear evidence-based guidance on optimal
      management.

PMID- 11251338
TI  - Causes of thrombophilia yet to be discovered: a personal view.
AB  - Prediction of genetic risk factors for venous thrombosis might best be left for
      only wise soothsayers. Nonetheless, based on the principle that
      hypercoagulability, either systemic or vascular-bed-specific, predisposes to
      thrombosis, we venture some speculations. Hyperactivity of platelets could be
      caused by elevated numbers of surface glycoproteins or defective signal
      transduction pathways. The reported efficacy of aspirin for prevention of venous
      thrombosis is consistent with the prediction that certain platelet defects may
      increase the risk of venous thrombosis. Hyperlipidaemia is associated with
      hypercoagulability, and lipoproteins exhibit procoagulant (e.g. triglyceride-rich
      particles and oxidized low-density lipoprotein) or anticoagulant (e.g. high
      density-lipoprotein's cofactor activity for activated protein C/protein S)
      activities. This leads to the prediction that defects in lipids and/or
      lipoproteins may increase the risk for venous thrombosis. Interestingly, statins
      were recently reported to prevent the occurrence of venous thrombosis in the HERS
      (Heart and Estrogen/Progestin Replacement) trial. We also predict that new
      defects in the protein C pathway (e.g. defective endothelial protein C receptor
      or novel cofactors for activated protein C/protein S) will be discovered. Risk
      factors affecting the majority of patients will likely involve new single
      nucleotide polymorphisms (SNPs) like the factor V nt G1691A or prothrombin nt
      G20210A SNPs. The Human Genome Project will soon accelerate discovery of new SNPs
      that are risk factors for venous thrombosis.

PMID- 11251339
TI  - Does inflammation contribute to thrombotic events?
AB  - Recent studies have focused on a myriad of mechanisms by which inflammation can
      potentiate blood clotting. Inflammatory mediators like endotoxin and tissue
      necrosis factor (TNF)-alpha can cause the expression of tissue factor on
      monocytes and, possibly, endothelium, thereby initiating the coagulation cascade.
      Activation of the complement system can lead to exposure of membrane surfaces
      capable of amplifying the initial tissue factor stimulus by facilitating the
      assembly of the factor VIIIa-factor IXa and the factor Xa-factor Va complexes.
      Inflammatory mediators, particularly interleukin-6, can also increase the levels
      of fibrinogen, an acute-phase reactant. In addition, the inflammatory mediators
      can elevate the levels of plasminogen activator inhibitor, thus suppressing the
      fibrinolytic system. These studies alone, however, do not prove that inflammation
      can trigger clinically relevant thrombus formation in vivo. For instance, TNF
      alpha has been studied in cancer patients as a potential cure for cancer, and
      even though these patients are hypercoaguable, thrombosis was not commonly
      observed as a side effect of the near-lethal doses of TNF-alpha that were
      administered. Based on primate studies, inflammatory mediators like TNF-alpha can
      promote clot deposition effectively only if there is reduced flow and inhibition
      of the natural anticoagulant pathways. The requirement for multiple simultaneous
      injurious events probably explains why inflammation alone is not observed as a
      major cause of thrombosis.

PMID- 11251340
TI  - Cellular consequences upon factor VIIa binding to tissue factor.
AB  - Tissue factor (TF) is a cell-surface-bound glycoprotein that binds the zymogen,
      factor (F) VII, and the active serine protease, FVIIa. The FVIIa/TF complex is
      the major activator of coagulation in vivo. Under normal physiological
      conditions, TF is expressed only on extravascular sites and perivascularly in the
      adventitial layer of blood vessels. Although not normally expressed by cells
      within the circulation, TF can be induced in monocytes and endothelial cells.
      Also, several malignant cells express high levels of TF. Recent reports have
      shown that FVIIa binding to TF can influence a number of biological functions,
      such as angiogenesis and cancer metastasis. TF also seems to play an important
      role in cell adhesion and migration. The intracellular signalling is independent
      of downstream activation of the blood coagulation cascade. FVIIa/TF seems to
      transduce signalling by two distinct mechanisms: one independent of the
      cytoplasmatic domain but dependent on the proteolytic activity of FVIIa, and one
      dependent on the cytoplasmatic domain of TF.

PMID- 11251341
TI  - Physiological function of tissue factor pathway inhibitor and interaction with
      heparins.
AB  - Tissue factor pathway inhibitor (TFPI) is now recognized as a major physiological
      anticoagulant. Its main role is to modulate factor VIIa/tissue factor catalytic
      activity. Another important role is to potentiate the effect of heparins. TFPI is
      released from the vascular endothelium after injection of either unfractionated
      heparin (UFH) or low-molecular-weight heparins (LMWHs), which may then provide
      high concentrations of TFPI at sites of tissue damage and ongoing thrombosis. In
      dilute prothrombin-time-based assays, released TFPI contributes approximately one
      third to the anticoagulant effect of heparin, the remaining being accounted for
      by antithrombin. Released TFPI, but not plasma TFPI, contains the basic carboxy
      terminal tail which is important for the anticoagulant effect. UFH and LMWH exert
      differential effects on intravascular TFPI. UFH, but not LMWH, given in
      therapeutic doses, is associated with a progressive depletion of TFPI, which is
      associated with a strong rebound activation of coagulation after cessation of
      treatment. Such depletion may explain the apparent superior efficacy of LMWH
      observed in clinical trials.

PMID- 11251342
TI  - Which antiphospholipid antibodies should be measured in the antiphospholipid
      syndrome?
AB  - The results of an analysis of studies published over a 10-year period that
      addressed the association between antiphospholipid antibodies (aPLs) and
      thromboembolic events in patients with the antiphospholipid syndrome (APS) are
      reported. It would appear that lupus anticoagulants are the strongest risk factor
      for thromboembolic events in aPL-positive patients. Consequently, it is suggested
      that all patients with clinical manifestations of APS should be tested for these
      antibodies. On the other hand, the results do not unequivocally show that
      measurement of anticardiolipin antibodies is of help in defining the thrombotic
      risk of patients. Furthermore, they only partially support the notion that anti
      beta 2-glycoprotein I and antiprothrombin antibodies may be independent risk
      factors for thrombosis.

PMID- 11251344
TI  - Preventing venous thromboembolism in general medical inpatients and after an
      ischaemic stroke.
AB  - Clinical trials and meta-analyses have shown that low-molecular-weight heparin
      and unfractionated heparin are effective in preventing deep vein thrombosis (DVT)
      in acutely ill medical inpatients who are at risk as they are likely to be
      bedridden for 6 days or more. It is not known, however, if such prophylaxis can
      also reduce the likelihood of fatal pulmonary embolism or decrease all-causes
      mortality in this patient population. No recommendations can be made regarding
      thromboprophylaxis in those at a lower risk of venous thromboembolism or in short
      stay inpatients, as these have not yet undergone clinical trial. Current evidence
      suggests that high doses of heparin should be avoided after an acute ischaemic
      stroke, as the results of recent large trials suggest any potential treatment
      benefit in preventing DVT is cancelled by the increased intracranial bleeding
      risk caused from the underlying disease.

PMID- 11251345
TI  - Risk assessment and prophylaxis of venous thromboembolism in non-surgical
      patients: cancer as a risk factor.
AB  - It is well documented that cancer patients undergoing surgery are at a
      sufficiently high risk of developing venous thromboembolism (VTE) to justify the
      routine use of prophylactic anticoagulant therapy. However, despite many studies
      showing an increased incidence of VTE associated with the use of chemotherapy in
      patients with breast carcinoma and with the use of indwelling venous access
      catheters in patients with various kinds of cancer, thromboprophylactic
      strategies are not yet widely used.

PMID- 11251346
TI  - Risk assessment and prophylaxis of venous thromboembolism in acutely and/or
      critically ill patients.
AB  - Both undetected and clinically evident venous thrombosis and venous
      thromboembolism (VTE) can seriously impact the prognosis of acutely and/or
      critically ill patients. Pulmonary embolism (PE) is harder to diagnose in the
      acutely and/or critically ill, many of whom also have developed respiratory
      failure for other reasons. Deep vein thrombosis (DVT) of the upper and lower
      extremities can subsequently complicate insertion of central venous catheters,
      leading to PE, sepsis and septic shock. Recovery from the original critical
      illness (e.g. weaning from mechanical ventilation) can be adversely affected by
      these complications. There are recent data suggesting that, for prophylaxis, low
      molecular-weight heparin (LMWH) is more effective than unfractionated heparin
      (UFH) in critically ill trauma patients, and that high-dose LMWH is more
      effective than placebo or low-dose LMWH in seriously ill medical patients. In
      both populations, LMWH appeared safe. While LMWH appears superior to UFH in acute
      stroke patients to prevent venographically-proven lower-extremity DVT, whether it
      provides a superior long-term outcome after acute stroke is uncertain. One study
      found that a high dosage of the LMWH dalteparin was more effective than placebo
      in preventing left ventricular thrombi after acute myocardial infarction, but
      there was a significant safety cost. Current questions surrounding prophylaxis of
      VTE and the use of LMWH in acutely and/or critically ill patients include whether
      monitoring levels and dosage adjustment in some of these patients would improve
      outcome, and whether the diagnosis of VTE can be improved so that treatment can
      be instituted when prophylaxis has failed.

PMID- 11251348
TI  - Death after joint replacement.
AB  - This review considers the incidence of fatal pulmonary embolism following lower
      limb arthroplasty and femur neck fracture and considers whether some of these
      deaths are preventable. The data considered refer to short-term in-hospital
      prophylaxis with low-molecular-weight heparin and unfractionated heparin.
      Mortality rates depend on the type of surgery, with fracture of the femur being
      associated with the highest rates and knee replacement associated with the
      lowest. Short-term prophylaxis with dalteparin does appear to reduce the risk of
      death, but the risk extends well beyond discharge from hospital. Studies of
      extended out-of-hospital prophylaxis in order to reduce deaths related to
      thromboembolism are warranted.

PMID- 11251349
TI  - Extended thromboprophylaxis following lower limb arthroplasty: what do the
      clinical trials mean?
AB  - Patients undergoing major orthopaedic surgery are at high risk of thromboembolic
      complications. Of the available options for pharmacologic prophylaxis, the low
      molecular-weight heparins (LMWHs) have been shown to be most effective in
      reducing the incidence of venous thromboembolic complications and are well
      tolerated. However, as the risk of venous thromboembolism persists for several
      weeks post-discharge, there is controversy regarding the ideal duration of
      prophylaxis. Six recent studies have examined the efficacy and safety of
      prolonged prophylaxis in this setting. Five of these studies have demonstrated
      that prolonged LMWH prophylaxis (either enoxaparin or dalteparin) for 4--5 weeks
      is beneficial and significantly superior to conventional prophylaxis for 7--15
      days. The other study, using ardeparin, examined clinical endpoints and showed a
      minor trend but no significant reduction in these events. Furthermore, two of the
      studies -- one with enoxaparin and one with dalteparin -- also demonstrated a
      significant reduction in the incidence of proximal deep vein thrombosis. Analysis
      of all clinical events from the five studies that have published that information
      shows a halving or 51% reduction in favour of prolonged prophylaxis. On the basis
      of current evidence, prolonged thromboprophylaxis with LMWH for up to 35 days
      after major orthopaedic surgery is recommended.

PMID- 11251350
TI  - New insights into extended prophylaxis after orthopaedic surgery - the North
      American Fragmin Trial experience.
AB  - It is well-known that peri-operative and post-operative venous thrombosis are
      common. Trials in Europe have shown that extended out-of-hospital prophylaxis
      with a low-molecular-weight heparin reduces the rate of deep vein thrombosis in
      patients undergoing elective hip surgery. North American investigators of limited
      outcome descriptive studies, however, have suggested that out-of-hospital
      prophylaxis is not necessary. To resolve this uncertainty, NAFT (North American
      Fragmin Trial) was conducted, the results of which are summarized in this paper.
      The findings of NAFT support the favourable findings of the European studies on
      extended prophylaxis. Furthermore, European data have shown extended out-of
      hospital prophylaxis to be cost-effective. On the basis of the aggregate data, it
      is felt that the A2 recommendation made by the Fifth American College of Chest
      Physicians consensus conference for extended prophylaxis should be changed to an
      A1 recommendation.

PMID- 11251351
TI  - Continuing out-of-hospital prophylaxis following major orthopaedic surgery: what
      now?
AB  - Post-surgical deep vein thrombosis (DVT) is often underdiagnosed by clinical
      assessment alone. Subclinical DVT is a major source of pulmonary embolism, which
      is an important cause of death, particularly following total hip replacement
      surgery. Results from pathophysiological studies and recently conducted,
      prospective double-blind venographic studies in Europe and North America suggest
      that, in patients undergoing total hip replacement surgery, thromboprophylaxis
      with a low-molecular-weight heparin should be continued for at least 5 weeks post
      operatively to minimize this serious complication.

PMID- 11251353
TI  - Low-molecular-weight heparin as a bridge to timely revascularization in unstable
      coronary artery disease -- an update of the Fragmin during Instability in
      Coronary Artery Disease II Trial.
AB  - This article summarizes the design and findings -- both at 3 months and at 1 year
      follow-up -- of the Fragmin during Instability in Coronary Artery Disease (FRISC)
      II trial. This multicentre randomized trial compared both an early invasive with
      an early non-invasive stategy, and prolonged treatment with dalteparin as opposed
      to placebo, in patients with unstable coronary artery disease. The results show
      that an early invasive strategy with coronary angiography and, if appropriate,
      revascularization procedures within 7 days after admission reduces the subsequent
      rate of mortality and myocardial infarction. The benefits of the invasive
      treatment were noticeably more marked in patients with any high-risk indicator --
      for example, male gender, age above 65 years, previous severe angina, or signs of
      ischaemia (ST depression on ECG) or of myocardial damage (elevated levels of
      troponin T). Treatment with dalteparin reduced the risk of death and myocardial
      infarction in high-risk (i.e. troponin-positive) patients, particularly during
      the first month of treatment. However, continuation with dalteparin therapy after
      revascularization procedures conferred no benefit. It is concluded that extended
      treatment with dalteparin is useful as a bridge to revascularization in this high
      risk subgroup of patients with unstable coronary artery disease.

PMID- 11251354
TI  - Low-molecular-weight heparin and other antithrombotic agents in the setting of a
      fast-track revascularization in unstable coronary artery disease.
AB  - Revascularization procedures and particularly percutaneous transluminal coronary
      angioplasty are being performed more and more often in patients with unstable
      coronary artery disease, despite the fact that these procedures are known to
      carry a higher risk in such patients than in those with stable disease. This
      article reviews studies that have investigated the potential of modern
      antithrombotic therapy -- low-molecular-weight heparin, anti-Xa agents, direct
      antithrombin inhibitors and glycoprotein IIb/IIIa inhibitors -- to reduce the
      post-procedural event rate in such patients. The results are promising.

PMID- 11251355
TI  - Low-molecular-weight heparin and other antithrombotic agents in the setting of a
      primarily medical treatment of unstable coronary artery disease.
AB  - Antithrombotic treatment of acute coronary syndromes (ACS) comprises aspirin and
      (low-molecular-weight) heparin. Adjunctive treatment with intravenous
      glycoprotein IIb/IIIa receptor antagonists may be used in high-risk individuals,
      especially when they undergo percutaneous coronary interventions. Results from
      large-scale trials studying the efficacy and safety of oral glycoprotein IIb/IIIa
      blockers in patients with ACS have been disappointing. Thrombolytic therapy is
      not indicated in ACS.

PMID- 11251357
TI  - Cost-effectiveness of prolonged out-of-hospital prophylaxis with low-molecular
      weight heparin following total hip replacement.
AB  - Several studies have demonstrated that prolongation of thromboprophylaxis after
      elective hip replacement significantly reduces the frequency of venographically
      demonstrated deep vein thrombosis. This paper reports an economic evaluation of
      prolonged prophylaxis with low-molecular-weight heparin (LMWH), based on outcome
      data from one of these trials. Analysis showed a net saving per patient of 3,400
      Swedish kronor. Consequently, if the costs of administering the LMWH -- which
      includes the cost of teaching the patient to self-administer whilst in hospital
      and the cost of a follow-up visit by a district nurse to ensure compliance -- are
      below this amount, the intervention will prove to be cost saving.

PMID- 11251358
TI  - Does low-molecular-weight heparin reduce the costs of venous thromboembolism
      treatment?
AB  - The development of low-molecular-weight heparins (LMWHs) has revolutionized the
      dominant treatment strategy of established deep vein thrombosis and pulmonary
      embolism. In a further attempt to simplify treatment, outpatient management using
      LMWH has been proposed for these patients. This management strategy has now been
      shown to be as safe and effective as hospital treatment in a number of large
      clinical trials. The question remains whether such an out-of-hospital treatment
      strategy actually reduces costs. This paper summarizes the economic evaluations
      reported in the literature. Two large economic evaluations, based on
      prospectively collected data on resource use, have been reported. Both pointed to
      a large reduction in costs of 60% or more. The size of the cost reduction depends
      on the proportion of patients managed at home. Several studies show that
      approximately 80% qualify for out-of-hospital treatment. Local facilities for
      organizing home care may put an upper limit on this proportion. From a societal
      perspective, the economic evidence in favour of outpatient treatment with LMWH
      presents a rare case of dominance: a situation of reduced costs with no
      concessions in clinical outcomes. Nevertheless, attention should be paid to the
      parties that will bear the healthcare costs generated by the replacement of
      inpatient care by outpatient care.

PMID- 11251359
TI  - Thromboprophylaxis with low-molecular-weight heparin: economic considerations.
AB  - Postoperative thromboembolic events are a major cost factor for every healthcare
      system. Although thromboprophylaxis carries its own costs, the application of a
      thromboprophylactic regimen is cost-effective in most instances, at least in high
      risk patients. A regimen of general postoperative prevention of deep vein
      thrombosis is always more cost-effective than surveillance programmes with
      treatment after diagnosis, and is almost always more cost-effective than no
      prophylaxis. For patients with a high risk of postoperative thromboembolism, such
      as after orthopaedic surgery, low-molecular-weight heparins have a rather clear
      advantage over prophylaxis with unfractionated heparin and warfarin, also in
      terms of cost- effectiveness. With regard to moderate-risk patients, such as
      after general surgery, the economic benefits are less clear. However, since the
      results of economic analyses are heavily dependent on the healthcare system, and
      since there are methodological difficulties and uncertainties connected with the
      analyses, the implications are difficult -- if not impossible -- to generalize.
      There is an urgent need for further prospective studies, which should be
      performed with defined economic variables a priori and in close cooperation with
      health economists.

PMID- 11251361
TI  - Low-molecular-weight heparins: are they interchangeable?
AB  - Unfractionated heparin (UFH) has been used as an antithrombotic agent in the
      treatment of various clinical entities for over 60 years. Low-molecular-weight
      heparin (LMWH) com- pounds have gradually replaced UFH for these indications as
      they have several advantages, including subcutaneous administration and the lack
      of need for laboratory monitoring. Ever since their introduction, there has been
      discussion about whether LMWH compounds differ in their efficacy and safety. The
      best answer is given by direct comparison of two or more preparations; however,
      such trials are very scarce. Comparison using classical meta-analysis is limited
      as only a small number of trials with the respective low-molecular-weight heparin
      compounds are available. The objective of the present analysis has been to use a
      novel way of plotting the odds ratios of the different studies to compare the
      efficacy and safety of different LMWH compounds in the initial treatment of
      patients with venous thromboembolism. Classical meta-analysis revealed reductions
      in safety and efficacy of 30--40% in favour of LMWHs. Contrasting the log odds
      ratios of efficacy and safety indicated that there is no conclusive evidence that
      LMWHs have intrinsic different safety and efficacy profiles.

PMID- 11251362
TI  - Low-molecular-weight heparins in the management of unstable angina.
AB  - Low-molecular-weight heparins (LMWHs) are derivatives of unfractionated heparin
      (UFH) and have a more favourable pharmacokinetic profile and a more predictable
      anticoagulant effect than UFH. These features allow the subcutaneous injection of
      weight-adjusted doses of LMWHs without monitoring of blood coagulation, and this
      results in cost savings. Clinical trials have shown that combined therapy with
      aspirin and LMWHs is significantly more effective than aspirin alone in reducing
      the risk of cardiac events in the acute treatment of patients affected by
      unstable angina. LMWHs have also been shown to be at least as safe and effective
      as UFH in reducing the incidence of death and myocardial infarction in patients
      with unstable angina. LMWHs appear to be at least as safe as UFH with regard to
      major bleeding risk. When given as extended therapy, LMWHs have been shown to be
      superior to placebo at 30 and 45 days, with an acceptable risk of bleeding.
      Additionally, LMWHs can be used as a 'bridge' to revascularization in patients
      for whom early invasive treatment is not readily available.

PMID- 11251367
TI  - Growth hormone response to a growth hormone-releasing hormone stimulation test in
      a population-based study following cranial irradiation of childhood brain tumors.
AB  - Children with brain tumors are at high risk of developing growth hormone
      deficiency (GHD) after cranial irradiation (CI) if the hypothalamus/pituitary
      (HP) axis falls within the fields of irradiation. The biological effective dose
      (BED) of irradiation to the HP region was determined, since BED gives a means of
      expressing the biological effect of various irradiation treatment schedules in a
      uniform way. Hypothalamic versus pituitary damage as cause of GHD was
      distinguished in 62 patients by comparing the growth hormone (GH) peak response
      to an insulin tolerance test (ITT)/arginine stimulation test and the GH response
      to a growth hormone-releasing hormone (GHRH) stimulation test. Peak GH response
      to a GHRH test was significantly higher (median 7.3 mU/l; range: 0.5--79.0 mU/l)
      than that of an ITT/arginine test (median 4.7 mU/l; range: 0.01--75.0 mU/l) (p =
      0.017). Peak GH after a GHRH test was significantly inversely correlated to
      follow-up time (r(s) = -0.46, p < 0.0001) and to BED (R(s) = -0.28, p = 0.03),
      and both were found to be of significance in a multivariante regression analysis.
      We speculate that a significant number of patients developed hypothalamic
      radiation-induced damage to the GHRH secreting neurons, and secondary to this the
      pituitary gland developed decreased responsiveness to GHRH following CI in
      childhood.

PMID- 11251368
TI  - Significance of basal IGF-I, IGFBP-3 and IGFBP-2 measurements in the diagnostics
      of short stature in children.
AB  - The role of IGF-I and IGFBP-3 measurements in the diagnostic work-up of short
      children is established but remains controversial. Little information exists on
      the value of IGFBP-2 measurements. Based on reference data established in 388
      children we have reinvestigated the issue, using data from 392 short children who
      underwent the same diagnostic procedures between 1987 and 1998 (GHD, n = 187; non
      GHD, n = 205, including patients with ISS, n = 76; IUGR, n = 46; and TS, n = 83).
      In comparing IGF-I, IGFBP-3 and IGFBP-2 serum levels of GHD and ISS children with
      reference data, we calculated the sensitivity, specificity, efficiency and
      positive predictive value for the diagnosis of GHD. The overall sensitivity of
      the parameters was high, the rank order being as follows: IGF-I >IGFBP-3 >IGFBP-2
      (75, 67 and 62%, respectively). In contrast, the specificity was relatively low:
      IGFBP-3 >IGFBP-2 >IGF-I (50, 50 and 32%, respectively). The efficiency and
      positive predictive value of parameters was in the order of 40, 60 and 70--80%,
      respectively. In repeated measurements, the recorded basal levels of IGF-I and
      IGFBP-3 showed an overall narrow range of variation. We conclude that the
      determination of basal IGF parameters is, together with anthropometry and imaging
      techniques, an indispensable tool for differentiating between GHD and ISS; and
      that IGFBP-2 plays an additional role in this process.

PMID- 11251369
TI  - Glucocorticoid effects on the diurnal rhythm of circulating leptin levels.
AB  - It is known that circulating leptin shows diurnal variation with a nocturnal
      rise; however, the mechanisms generating this rhythm have not been fully
      elucidated. Glucocorticoids are a potent stimulator of leptin secretion, and
      there is a reciprocal relationship between circulating leptin and glucocorticoid
      levels. We hypothesized that glucocorticoids could modulate the diurnal rhythm of
      circulating leptin. We therefore explored the diurnal variation of leptin under
      situations in which subjects showed no or some shift of glucocorticoid diurnal
      rhythm, such as prednisolone-administered humans, and adrenalectomized and
      corticosterone-replaced (ADX+B) rats. The peak level of plasma cortisol
      immunoreactivity was shifted from early morning to noon by prednisolone
      administration. The nocturnal increment of plasma leptin in prednisolone
      administered patients (71.2 +/- 14.2% from 08:00 h value) was significantly
      greater than that in normal volunteers (12.2 +/- 7.5% from 08:00 h value), but
      the timing of nadir and the peak of plasma leptin was not shifted. In normal
      rats, the plasma concentration of leptin showed the diurnal rhythm with the
      bottom at 16:00 h and the top between midnight and early morning. The amplitude
      of leptin diurnal rhythm was significantly reduced in ADX+B rats (08:00 h: 3.0 +/
      0.2, 16:00 h: 2.7 +/- 0.2, 00:00 h; 3.7 +/- 0.2 ng/ml) compared with sham
      operated rats (08:00 h: 3.0 +/- 0.2, 16:00 h 2.2 +/- 0.2, 00:00 h: 4.7 +/- 0.4
      ng/ml); but ADX+B rats still retained similar timing of nadir and the peak of
      plasma leptin as observed in sham rats. These results indicate that
      glucocorticoids enhance the amplitude of leptin diurnal rhythm, and are
      consistent with previous findings showing that glucocorticoids increase leptin
      secretion. Glucocorticoids appear to play modulatory, but not essential roles in
      generating leptin diurnal rhythm.

PMID- 11251370
TI  - Influence of octreotide and tamoxifen on tumor growth and liver metastasis in N
      nitrosobis(2-oxopropyl)amine-induced pancreatic cancer in Syrian hamsters.
AB  - In prospective clinical trials single octreotide therapy or combined therapy with
      tamoxifen has improved the quality of life and survival time in patients with
      pancreatic cancer. In this study we analyzed the influence of octreotide and
      tamoxifen on tumor growth and liver metastases in chemically induced pancreatic
      adenocarcinoma in Syrian hamsters. Octreotide alone and the combined therapy
      (octreotide/tamoxifen) decreased the incidence of macroscopic pancreatic
      carcinomas as well as the number and size of liver metastases. The combined
      therapy showed no superior effect to octreotide alone. Furthermore, there was no
      difference between the tamoxifen and the control group.

PMID- 11251371
TI  - Effect of excitatory amino acids on serum TSH and thyroid hormone levels in
      freely moving rats.
AB  - The actions of glutamate (L-Glu), and glutamate receptor agonists on serum
      thyroid hormones (T4 and T3) and TSH levels have been studied in conscious and
      freely moving adult male rats. The excitatory amino acids (EAA), L-Glu, N-methyl
      D-aspartate (NMDA), kainic acid (KA) and domoic acid (Dom) were administered
      intraperitoneally. Blood samples were collected through a cannula implanted in
      the rats jugular 0--60 min after injection. Thyroid hormone concentrations were
      measured by enzyme immunoassay, and thyrotrophin (TSH) concentrations were
      determined by radioimmunoassay. The results showed that L-Glu (20 and 25 mg/kg)
      and NMDA (25 mg/kg) increased serum thyroxine (T4), triiodothyronine (T3) and TSH
      concentrations. Serum thyroid hormone levels increased 30 min after treatment,
      while serum TSH levels increased 5 min after i.p. administration, in both cases
      serum levels remained elevated during one hour. Injection of the non-NMDA
      glutamatergic agonists KA (30 mg/kg) and Dom (1 mg/kg) produced an increase in
      serum thyroid hormones and TSH levels. These results suggest the importance of
      EAAs in the regulation of hormone secretion from the pituitary-thyroid axis, as
      well as the importance of the NMDA and non-NMDA receptors in this stimulatory
      effect.

PMID- 11251372
TI  - Serum inhibin A and inhibin B in central precocious puberty before and during
      treatment with GnRH agonists.
AB  - Serum levels of the gonadal hormones inhibin A and inhibin B are undetectable or
      low in prepubertal girls, and rise during puberty. In girls with central
      precocious puberty (CPP) the hypothalamic-pituitary-gonadal axis is prematurely
      activated, if the girl is thereafter treated with GnRH agonists both
      gonadotropins and estradiol levels become suppressed. We therefore investigated
      serum levels of inhibin A and inhibin B in girls with CPP at diagnosis and during
      treatment in order to test the hypothesis that inhibin secretion would increase
      and decrease in parallel with the activation and suppression of the hypothalamic
      pituitary-gonadal axis. Serum levels of inhibin A and inhibin B were
      significantly (p < 0.0005) elevated in 42 girls at diagnosis of CPP (inhibin A: 7
      pg/ml (<7--139), inhibin B: 80 pg/ml (<20--294) (median, range)) compared to
      levels in age-matched healthy schoolgirls (inhibin A: all values <7 pg/ml,
      inhibin B: 21 pg/ml (<20--122) (median, range)), but were appropriate for Tanner
      stage. During treatment with GnRH agonist (intranasal buserelin and oral
      cyproterone acetate, treatment group 1, n = 23, or triptorelin depot injections,
      treatment group 2, n = 19) levels of both hormones fell significantly (p =
      0.002). There was a significantly (p = 0.003) greater fall in inhibin B levels
      during treatment in group 2 compared to group 1, with inhibin B levels now lying
      below (group 2: <20 pg/ml (<20--68)) rather than within (group 1: 34.5 pg/ml (<20
      -93)) the age-appropriate range. It is concluded that levels of inhibin A and
      inhibin B are elevated and suppressed in concert with activation and suppression
      of the hypothalamo-pituitary-gonadal axis in girls with CPP, supporting the
      concept that ovarian inhibin secretion is dynamically regulated by gonadotropin
      stimulation.

PMID- 11251373
TI  - Evaluation of cutaneous modifications in seventy-seven growth hormone-deficient
      children.
AB  - Cutaneous parameters such as dermal thickness, stiffness, elasticity, skin
      surface lipid and hydration were evaluated using noninvasive methods in 77 growth
      hormone-deficient (GHD) children before replacement therapy and in 70 non-GHD
      children. We showed that in GHD children, dermis was thinner (0.70 +/- 0.10 vs.
      0.80 +/- 0.10 mm, p < 0.0001 for prepubertal children and 0.81 +/- 0.10 vs. 0.94
      +/- 0.11 mm, p < 0.0001 for pubertal children), stiffer (178.5 +/- 57.3 vs.
      113.09 +/- 37 kPa, p < 0.0001 for prepubertal children and 172.5 +/- 61.7 vs.
      117.3 +/- 42.5 kPa for pubertal children, p < 0.001) and less elastic (0.44 +/-
      0.09 vs. 0.39 +/- 0.06 (nonelasticity index), p < 0.01 for prepubertal children
      and 0.39 +/- 0.05 vs. 0.33 +/- 0.04, p < 0.001 for pubertal children) compared to
      controls. Fourteen GHD children were re-evaluated after 1 year of GH treatment:
      dermal thickness and skin stiffness were significantly improved (p < 0.001 and p
      < 0.05 respectively) while elasticity was not modified. During the same period,
      11 controls did not show any significant cutaneous modification. IGF-1 values,
      but not IGFBP-3 values, correlated positively with dermal thickness in GHD
      children, before and after 1 year of GH treatment. To conclude, GHD children
      exhibited specific cutaneous modifications. In a subset of GHD children, we
      showed that these modifications were influenced by GH treatment. More extensive
      studies are needed to see if these changes correlated with other GH effects.

PMID- 11251374
TI  - Central diabetes insipidus as the first manifestation of neurosarcoidosis in a 10
      year-old girl.
AB  - Central diabetes insipidus with thickening of the pituitary stalk has been
      demonstrated in adults with Langerhans cell histiocytosis (LCH), tuberculosis or
      sarcoidosis, and in children with LCH. We present a 10.5-year-old girl with
      central diabetes insipidus. Magnetic resonance imaging (MRI) revealed thickening
      of the central part of the pituitary stalk and multiple hyperintense lesions in
      the frontal white matter on T(2)-weighted images. Laboratory findings were normal
      except for an elevated serum angiotensin-converting enzyme (ACE) level. The MRI
      findings together with the elevated serum ACE level highly suggest the diagnosis
      of sarcoidosis. We conclude that central diabetes insipidus can be the first
      clinical manifestation of sarcoidosis in children.

PMID- 11251375
TI  - Acute thyroiditis in a child: misleading result of fine-needle aspiration biopsy.
AB  - We report a case of acute thyroiditis in a 6-year-old girl, whose initial
      borderline clinical and sonographic data, coupled with the absence of leucocytes
      and bacteria on the fine-needle aspiration biopsy, led to the reversal of the
      initial diagnostic impression of acute thyroiditis and the institution of an
      inappropriate glucocorticoid treatment. Since both diseases are rare in the
      paediatric age group and therapy is completely different, we conclude that in
      borderline cases careful clinical observation and the response to the initial
      antibiotic therapy should be considered more reliable than any single morphologic
      or microbiologic result. We also suggest that acute bacterial thyroiditis could
      be usefully classified into two forms, suppurative and non-suppurative.

PMID- 11251376
TI  - Update on antiviral DNA vaccine research (1998-2000).
AB  - DNA vaccines can induce protective cellular and humoral immune responses and have
      therefore been used during the last decade to develop vaccines against a variety
      of different pathogens. Because current antiviral vaccines predominantly generate
      humoral immunity, DNA immunization may be especially useful to provide long-term
      protection against viral diseases that also require cellular immunity (e.g. HIV).
      A significant number of articles published in the field of DNA vaccines are
      dealing with viral diseases, reflecting the need for better and alternative
      vaccination strategies against viruses. The success of DNA immunization depends
      on a variety of parameters (e.g. type of antigen, method of application and usage
      of adjuvants). Therefore, different strategies have been explored to modulate the
      induced immune response with respect to the requirements necessary to protect
      against a specific pathogen (e.g. induction of mucosal or cell-mediated
      immunity). The following article provides an update on different aspects of
      antiviral DNA vaccine research that have previously been reviewed by others.

PMID- 11251377
TI  - Optimization strategies for DNA vaccines.
AB  - DNA immunization is a relatively new vaccination strategy that involves the
      direct introduction into the host of plasmid DNA encoding the desired antigen.
      The DNA enters host cells and results in immune responses following in vivo
      expression of the antigen. Although DNA-based immunization works well in animal
      models for the induction of both humoral and cell-mediated immune responses, its
      success in humans has been limited. This paper discusses different approaches
      that have attempted to optimize DNA vaccines, and presents results evaluating
      some of these approaches in mice.

PMID- 11251378
TI  - Relative potency of cellular and humoral immune responses induced by DNA
      vaccination.
AB  - DNA vaccines can prime broad-based immune responses in small animal models. In
      the present study, we sought to evaluate the relative ability of DNA vaccines to
      induce humoral and cellular immune responses. Using a DNA vaccine encoding HIV
      gag in mice, we observed that CD8+ T cell responses were primed more readily than
      were antibody responses, particularly at low doses of DNA. These CD8+ T cell
      responses were detected in spleen cells, as well as at local sites such as the
      lung and draining lymph nodes. The potency of the HIV gag DNA vaccine used was
      sufficient to prime strong CTL responses in macaques, but only low to
      undetectable antibody responses. Therefore, DNA vaccines appear able to prime
      strong, broad CTL but only modest antibody responses. These results may have
      implications on the development of vaccines against infectious diseases where
      both CTL and antibody responses are desired, such as HIV.

PMID- 11251379
TI  - Improving DNA vaccines targeting viral infection.
AB  - DNA vaccination techniques have been recently under intensive investigation both
      preclinically and in human studies aimed at impacting viral infection.
      Collectively, DNA vaccines expressing viral antigens induce both antigen-specific
      humoral and cellular immune responses which in model systems are capable of
      impacting viral infection. However, in clinical settings the potency of this
      approach is still under investigation. Efficacy is improved in specific
      circumstances through the addition of immunomodulatory molecules including
      cytokines as plasmid cassettes or through modification of the numbers of specific
      CpG sequences present in the backbone. Furthermore, combined vaccination schemes
      have been an important research focus for generating enhanced immunogenicity
      against viral infections. The ultimate utility of these approaches to prevent
      viral infection will require more work. However, improvements in the potency and
      focus of DNA vaccines present us with new opportunities for both basic research
      into protective immunity as well as novel strategies for immune therapy and
      prophylaxis.

PMID- 11251380
TI  - Alphavirus vectors: applications for DNA vaccine production and gene expression.
AB  - Replication-deficient alphavirus vectors have been developed for efficient high
      level transgene expression. The broad host range of alphaviruses has allowed
      infection of a wide variety of mammalian cell lines and primary cultures.
      Particularly, G protein-coupled receptors have been expressed at high levels and
      subjected to binding and functional studies. Expression in suspension cultures
      has greatly facilitated production of large quantities of recombinant proteins
      for structural studies. Injection of recombinant alphavirus vectors into rodent
      brain resulted in local reporter gene expression. Highly neuron-specific
      expression was obtained in hippocampal slice cultures in vivo. Additionally,
      preliminary studies in animal models suggest that alphavirus vectors can be
      attractive candidates for gene therapy applications. Traditionally alphavirus
      vectors, either attenuated strains or replication-deficient particles, have been
      used to elicit efficient immune responses in animals. Recently, the application
      of alphaviruses has been extended to naked nucleic acids. Injection of DNA as
      well as RNA vectors has demonstrated efficient antigen production. In many cases,
      protection against lethal challenges has been obtained after immunization with
      alphavirus particles or nucleic acid vectors. Alphavirus vectors can therefore be
      considered as potentially promising vectors for vaccine production.

PMID- 11251381
TI  - Plasmid DNA vaccines: investigation of integration into host cellular DNA
      following intramuscular injection in mice.
AB  - The primary safety concern for DNA vaccines is their potential to integrate into
      the host cell genome. We describe an integration assay based on purification of
      high-molecular-weight genomic DNA away from free plasmid using gel
      electrophoresis, such that the genomic DNA can then be assayed for integrated
      plasmid using a sensitive PCR method. The assay sensitivity was approximately 1
      plasmid copy/microg DNA (representing approximately 150,000 diploid cells). Using
      this assay, we carried out integration studies of three different plasmid DNA
      vaccines, containing either the influenza hemagglutinin, influenza matrix or HIV
      gag gene. Six weeks after intramuscular injection, free plasmid was detected in
      treated muscle at levels ranging from approximately 1,000 to 4,000 copies/microg
      DNA. At 6 months, the plasmid levels ranged between 200 and 800 copies/microg
      DNA. Gel purification of genomic DNA revealed that essentially all of the
      detectable plasmid in treated quadriceps was extrachromosomal. If integration had
      occurred, the frequency was </= 1-8 integrations per 150,000 diploid cells, which
      would be at least three orders of magnitude below the spontaneous mutation rate.
      Our results suggest that the risk of mutation due to integration of plasmid DNA
      vaccines following intramuscular injection is negligible.

PMID- 11251382
TI  - Plasmid DNA vaccines: tissue distribution and effects of DNA sequence, adjuvants
      and delivery method on integration into host DNA.
AB  - A variety of factors could affect the frequency of integration of plasmid DNA
      vaccines into host cellular DNA, including DNA sequences within the plasmid, the
      expressed gene product (antigen), the formulation, delivery method, route of
      administration, and the type of cells exposed to the plasmid. In this report, we
      examined the tissue distribution and potential integration of plasmid DNA
      vaccines following intramuscular administration in mice and guinea pigs. We
      compared needle versus Biojector (needleless jet) delivery, examined the effect
      of aluminum phosphate adjuvants, compared the results of different plasmid DNA
      vaccines, and tested a gene (the human papilloma virus E7 gene) whose protein
      product is known to increase integration frequency in vitro. Six weeks following
      intramuscular injection, the vast majority of the plasmid was detected in the
      muscle and skin near the injection site; lower levels of plasmid were also
      detected in the draining lymph nodes. At early time points (1-7 days) after
      injection, a low level of systemic exposure could be detected. Occasionally,
      plasmid was detected in gonads, but it dissipated rapidly and was
      extrachromosomal - indicating a low risk of germline transmission. Aluminum
      phosphate adjuvant had no effect on the tissue distribution and did not result in
      a detectable increase in integration frequency. Biojector delivery, compared with
      needle injection, greatly increased the uptake of plasmid (particularly in skin
      at the injection site), but did not result in a detectable increase in
      integration frequency. Finally, injection of a plasmid DNA vaccine containing the
      human papilloma virus type 16 E7 gene, known to increase integration in vitro,
      did not result in detectable integration in mice. These results suggest that the
      risk of integration following intramuscular injection of plasmid DNA is low under
      a variety of experimental conditions.

PMID- 11251383
TI  - DNA vaccination for HIV-1 and SIV.
AB  - Control of the worldwide AIDS epidemic will only be achieved with a safe and
      effective prophylactic HIV-1 vaccine. DNA vaccination has recently emerged as a
      promising vaccine modality that can elicit both humoral and cellular immune
      responses. HIV-1- and SIV-specific immune responses have been elicited by DNA
      vaccines in both mice and nonhuman primates. However, these immune responses have
      not been capable of protecting nonhuman primates against pathogenic AIDS virus
      challenges. A number of approaches are therefore being investigated to augment
      DNA vaccine-elicited immune responses.

PMID- 11251384
TI  - DNA-encoding enzymatically active HIV-1 reverse transcriptase, but not the
      inactive mutant, confers resistance to experimental HIV-1 challenge.
AB  - The present study was undertaken to examine the immunogenicity of a single
      plasmid DNA representing the reverse transcriptase (RT) of HIV-1. Plasmids
      containing the enzymatically active RT as well as a mutated nonenzymatically
      active RT with nucleotide (nt)-binding motifs of YMDD and YMLL, respectively,
      were used to immunize mice. Both constructs induced similar good antibody and T
      cell responses, with a tendency towards antibody directed to peptides
      representing the active and mutated sites. Immunized mice were challenged with a
      murine pseudotype HIV-1/MuLV infected spleen cells. Seven out of 10 mice
      immunized with RT had no recoverable HIV-1, while 10 individuals immunized with
      the RT mutant and all the 18 controls had high levels of recoverable HIV-1. This
      indicates that mutation of RT reduces the desired immunogenicity.

PMID- 11251385
TI  - Human natural killer cells in asymptomatic human immunodeficiency virus-1
      infection.
AB  - OBJECTIVES: We evaluated whether DNA immunization with HIV-1 regulatory genes
      change natural killer (NK) effector cell activity. NK cells are the most
      important cells for the immediate host defense against virus-infected and tumor
      cells. We analyzed the NK activities of HIV-1-infected individuals against K562
      cells (the classical assay) as well as against a CD4+ cell line with and without
      HIV-1 infection. CD4+ T lymphocytes are the main target cells for HIV-1 infection
      in vivo. Various proportions of the CD4+ T lymphocyte population carry the HIV-1
      genome, produce virus and contribute to the systemic spread of HIV-1. METHODS:
      CD4+ cell lines were established through HTLV-1 transformation which made the
      cells susceptible to NK lysis. NK activity was then tested in a (51)Cr release
      assay. RESULTS: NK cells of asymptomatic HIV-infected individuals mediated
      considerable lytic activity against K562 cells as well as against the uninfected
      and HIV-1-infected CD4+ cell line, and so did the NK cells of HIV-1-infected
      patients on highly active antiretroviral treatment. CONCLUSION: DNA immunization
      with HIV-1-regulatory genes did not significantly change the NK effector cell
      activity.

PMID- 11251386
TI  - DNA-based immunization against Lyssaviruses.
AB  - Rabies is a fatal encephalomyelitis. Most cases occur in developing countries and
      are transmitted by dogs. Because of their high cost, cell culture vaccines have
      not totally replaced the unsafe brain-derived vaccines which are still used in
      many developing countries. Moreover, there will be a need for vaccines against
      rabies-related viruses against which classical vaccines are not always effective.
      DNA vaccines would, therefore, be a valuable alternative for the production of
      cheaper rabies vaccines against a larger spectrum of viruses. In this review we
      report published data on DNA-based immunization with sequences encoding rabies
      and rabies-related virus antigens.

PMID- 11251387
TI  - DNA vaccination against La Crosse virus.
AB  - For the development of effective conventional vaccines or DNA vaccines against
      viruses, the availability of suitable animal models is an essential prerequisite.
      For many recently emerging zoonotic viruses, suitable animal models are still
      missing. We have established a novel small animal model for DNA vaccines using
      mice lacking a functional interferon-alpha/beta receptor (IFNAR-1). IFNAR-1
      deficient mice are highly susceptible to many different viruses despite their
      ability to mount a normal humoral and cellular immune response. Taking advantage
      of this animal model, we show that mice can be completely protected from lethal
      challenge with a single injection of plasmid DNA encoding the viral envelope
      proteins G1 and G2. By contrast, vaccination with a plasmid encoding the internal
      nucleocapsid protein N had little effect. In an effort to enhance the protective
      immune response to N we assessed the efficacy of vaccination with plasmid DNA
      encoding N in combination with a plasmid encoding the cytokine IL-12 as adjuvant.
      IL-12 enhanced the survival of mice following viral challenge, but the effect was
      independent of N indicating the involvement of components of the innate immune
      system such as NK cells.

PMID- 11251388
TI  - Mechanism of protection against influenza A virus by DNA vaccine encoding the
      hemagglutinin gene.
AB  - Influenza A virus with its two major antigenic surface proteins hemagglutinin
      (HA) and neuraminidase (NA) is a widely used model to study DNA immunizations in
      mice and other animals. Natural protection against influenza A virus infection is
      mediated by antibodies, which mostly are not protective against antigenic shift
      or drift variants of the original virus. Therefore, it would be a major task to
      induce a protective cellular immune response to more conserved proteins or
      epitopes. Injection of plasmid encoding a viral antigen is known to induce
      cellular as well as humoral immunity. In this study we investigate the mechanism
      of protection after intramuscular vaccination of C57Bl/6 mice with a DNA vaccine
      encoding HA of influenza A/PR/8/34. After a single injection, only a small
      percentage of mice survive the lethal challenge with homologous virus. The amount
      of protection can be doubled by applying a booster injection. Furthermore, by
      coinjection of plasmids encoding cytokines GM-CSF and IL-12, respectively, nearly
      all of the mice are protected. Mice with specific defects in the cellular immune
      response [perforin knockout (P-/-) mice] and in the humoral immune response
      [IgD/IgM knockout (muMT) mice], respectively, have been immunized with HA DNA
      with or without cytokine DNA. Protection could only be induced in P-/- mice,
      whereas muMT mice succumbed to the infection. Moreover, when muMT mice were
      infected with only 0.75 x50% lethal dose they died all the same, whereby mice
      that had been depleted of CD8+ T cells before infection showed an even greater
      progression of illness. Altogether these results demonstrate that antibodies
      mediate protection after immunization with plasmid coding for HA of influenza A
      virus, and that booster immunizations and coinjection of plasmids encoding GM-CSF
      or IL-12 can improve this protection.

PMID- 11251389
TI  - DNA vaccines: development, standardization and regulation.
AB  - Nucleic acid vaccines contain nonvectored nucleic acids intended to be used as
      prophylactic vaccines in humans or animals. In addition to the Guidelines
      Assuring the Quality of DNA Vaccines published by the WHO, further standards for
      the manufacture and preclinical testing are being developed. Theoretical risks
      have been taken into account and assessed before human use has been considered.
      Legal requirements for clinical trials and licensing of nucleic vaccines are in
      place in Germany and other European member states which allow further testing and
      development of proprietary medicinal products based on nucleic acids and intended
      for prophylactic vaccination.

PMID- 11251390
TI  - Regional variations in the transport of interleukin-1alpha across the blood-brain
      barrier in ICR and aging SAMP8 mice.
AB  - OBJECTIVES: The blood-brain barrier (BBB) transports blood-borne interleukin
      1alpha (IL-1) into the brain by a saturable process. Here, we determined whether
      all regions of the brain could transport IL-1 and whether transport differed
      between ICR and SAMP8 mice, a strain which overexpresses amyloid beta protein
      (Abeta) with aging. METHODS: We used multiple-time regression analysis to measure
      the unidirectional influx rate (transport rate) of radioactively labeled IL-1 for
      10 brain regions in young (2 months old) ICR mice and in young and aged (17
      months old) SAMP8 mice. We also used radioactively labeled sucrose and albumin to
      determine whether the BBB was disrupted in aged SAMP8 mice. RESULTS: In young ICR
      mice, eight of the 10 brain regions transported IL-1, with the pons-medulla
      having the fastest transport rate (0.584 +/- 0.163 microl/g x min), but no
      statistically significant differences occurred among regions. In SAMP8 mice, only
      four regions transported IL-1. In young SAMP8 mice, the pons-medulla transported
      IL-1 faster than any other region (0.642 +/- 0.197 microl/g x min), a rate that
      was significantly different (p < 0.01) from each of the other regions. Aged SAMP8
      mice had a similar regional transport pattern to young SAMP8 mice, but there were
      no statistically significant differences among the four transporting regions.
      Sucrose and albumin spaces were not increased in aged SAMP8 mice, demonstrating
      an intact BBB. CONCLUSIONS: The smaller number of regions transporting IL-1 in
      SAMP8 mice as compared to ICR mice demonstrates a genetic influence on transport
      which could alter the ability of blood-borne IL-1 to directly affect brain
      functions. No evidence of BBB disruption was found in the aged SAMP8 mice from
      this colony.

PMID- 11251391
TI  - Development and sequels of intestinal inflammation in nematode-infected rats:
      role of mast cells and capsaicin-sensitive afferents.
AB  - OBJECTIVES: To determine whether intestinal mast cells and capsaicin-sensitive
      afferent nerves are involved in the development and sequels of Nippostrongylus
      brasiliensis-induced intestinal inflammation in rats. METHODS: Two series of
      experiments were performed. In the first series, six groups of 8 rats were used
      to study the effects of mast cell stabilization by ketotifen. In the second
      series, six groups of 6 rats were used to study the effects of gut extrinsic
      sensory neuron depletion by capsaicin. For each series, four groups of rats were
      infected with N. brasiliensis and two groups were not infected. RESULTS:
      Infection with N. brasiliensis resulted in an increase of myeloperoxidase (MPO)
      activity and mast cell numbers at day 12 postinfection; MPO returned to
      preinfection levels by day 35 while mast cell numbers remained elevated at that
      time. In ketotifen-treated infected rats, the increase of MPO at day 12 was less
      pronounced, but MPO activity remained elevated and mast cell numbers were
      increased at day 35. In capsaicin-treated infected rats, the MPO increase at day
      12 was augmented, and MPO was still not returned to preinfection values by day
      35; in contrast, the increase of mast cell numbers at days 12 and 35 was not
      modified by afferent nerve depletion. CONCLUSION: Mast cell stabilization
      decreased jejunal inflammation during the acute stage (day 12), but prolonged the
      inflammatory process until at least day 35 postinfection. The data also confirmed
      the protective role of gut extrinsic sensory neurons against intestinal
      inflammation in a model of nematode infection and revealed that these afferent
      nerves do not seem crucial for the development of nematode-induced
      hypermastocytosis.

PMID- 11251392
TI  - Specific serotonin reuptake inhibitor-induced decreases in lymphocyte activity
      require endogenous serotonin release.
AB  - OBJECTIVES: We have previously reported that acute administration of the specific
      serotonin reuptake inhibitor (SSRI), fluoxetine, resulted in a decrease in
      mitogen-induced blood lymphocyte proliferation. The present studies further
      examine the specificity of this response to serotonin reuptake systems and the
      potential role of endogenous serotonin in mediating these effects. METHODS: Male
      Sprague-Dawley rats were treated intraperitoneally with the SSRIs, fluoxetine (6
      10 mg/kg) or sertraline (20 mg/kg), dopamine and norepinephrine reuptake
      inhibitors, GBR 12909 and desipramine, respectively (6 mg/kg) or the serotonin
      precursor, 5-hydoxytryptophan (5-HTP, 50 mg/kg) 2 h prior to sacrifice. The
      serotonin-depleting agents, p-chlorophenylalanine (PCPA, 2 x 200 mg/kg) or the
      serotonin-lesioning agent, p-chloroamphetamine (PCA, 2 x 10 mg/kg) were
      administered intraperitoneally 5-7 days prior to fluoxetine (10 mg/kg)
      administration. RESULTS: Unlike the SSRIs, which significantly suppressed
      lymphocyte proliferation responses, selective norepinephrine or dopamine reuptake
      inhibition had no effect on lymphocyte proliferation. Elevation of extracellular
      serotonin levels with the serotonin precursor, 5-HTP, resulted in a similar
      decrease in lymphocyte proliferation as that seen with SSRI administration.
      Conversely, decreases in endogenous serotonin following PCA or PCPA treatment
      prevented the fluoxetine-induced decreases in lymphocyte proliferation.
      CONCLUSIONS: These results suggest that decreases in mitogen-induced lymphocyte
      proliferation following acute fluoxetine administration were due to elevations in
      extracellular serotonin following reuptake inhibition.

PMID- 11251393
TI  - Blockade of nitric oxide formation enhances thermal and behavioral responses in
      rats during turpentine abscess.
AB  - OBJECTIVE: The purpose of this study was to investigate the role of nitric oxide
      (NO) during the development of fever and other symptoms of sickness behavior
      (i.e. anorexia, cachexia) in response to localized tissue inflammation caused by
      injection of turpentine in freely moving biotelemetered rats. METHODS: To
      determine the role of NO in turpentine-induced fever, we injected the NO synthase
      (NOS) inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) intraperitoneally
      simultaneously or 5 h after turpentine injection. RESULTS: Rats responded with
      fever to intramuscular injection of 20 microl of turpentine that commenced 6 h
      after injection and reached peak values 11 h after injection. Although turpentine
      did not significantly alter food and water intake, it caused a drop in body
      weight. Rats injected with turpentine and treated with L-NAME responded with a
      substantial rise in fever, independently of the time of L-NAME injection. The
      rise in body temperature (T(b)) due to turpentine injection began slightly sooner
      and reached the maximal T(b) value faster in rats treated with L-NAME than in the
      ones treated with saline (control for L-NAME). The enhanced decrease in food and
      water intake in rats treated with a combination of L-NAME and turpentine was also
      observed. As a result, L-NAME-injected rats responded with a profound drop in
      body mass due to turpentine, independently of the time of L-NAME injection. L
      NAME alone did not affect food and water intake, but slightly suppressed the gain
      of body mass. CONCLUSION: These results indirectly indicate that NO is involved
      in pyrogenic and behavioral responses in rats during turpentine abscess.

PMID- 11251395
TI  - Frequency analysis of involuntary movements during wrist tracking: a way to
      identify ms patients with tremor who benefit from thalamotomy.
AB  - To identify those multiple sclerosis (MS) patients with disabling tremor who will
      benefit most from thalamotomy, measurements of frequency spectra of involuntary
      movements during visually guided wrist tracking were carried out in 11
      consecutive patients with MS before and after ventrolateral thalamotomy.
      Thalamotomy was significantly more effective if patients had disruptive action
      tremor which appeared as a single peak in the frequency spectra. Such patients
      showed an average reduction of nearly 80% in tremor magnitude after thalamotomy.
      In comparison, surgery produced an average reduction of only 30% in 3 other
      patients who had action tremor but showed multiple peaks in the frequency
      spectra. Frequency analysis of involuntary movements identifies those MS patients
      with disabling tremor who benefited most from thalamotomy.

PMID- 11251394
TI  - Interferon-gamma release in sympathetically denervated rat submaxillary lymph
      nodes.
AB  - OBJECTIVE: To examine the regulation of interferon (IFN)-gamma release by cells
      derived from submaxillary lymph nodes of rats subjected to an acute or chronic
      superior cervical ganglionectomy (SCGx). METHODS: A unilateral SCGx and a
      contralateral sham operation were performed. Twenty hours or 7 days later cells
      from submaxillary lymph nodes were incubated for 24 h without any additional
      treatment (experiment 1), after adding lipopolysaccharide or concanavalin A
      (experiment 2) or after adding norepinephrine (NE, 10(-8) M; experiment 3). IFN
      gamma concentration in the culture media was measured by ELISA. RESULTS: Compared
      to controls, cells obtained from lymph nodes at a time of degeneration of
      sympathetic nerve terminals released more IFN-gamma, whereas those derived from
      chronically SCGx lymph nodes released less IFN-gamma. Stimulation of IFN-gamma
      release by mitogens was detectable in the innervated or acutely denervated lymph
      nodes, but not in chronically denervated lymph nodes. When the effect of 10(-8) M
      NE on IFN-gamma release was tested, the neurotransmitter augmented cytokine
      release in cells prepared from chronically denervated lymph nodes only.
      CONCLUSION: The microenvironment provided by local sympathetic nerves is
      essential to enable an appropriate IFN-gamma release by submaxillary lymph node
      cells to occur.

PMID- 11251396
TI  - Technical data and complications of spinal cord stimulation: data from a
      randomized trial on critical limb ischemia.
AB  - This study was done to evaluate the effect of spinal cord stimulation (SCS) on
      critical limb ischemia and to report technical problems and complications. One
      hundred and twenty patients with critical limb ischemia were eligible for
      randomization between medical treatment and medical treatment plus SCS. Sixty
      received a spinal cord stimulator (Itrel II; Medtronic, Minneapolis, Minn., USA).
      Primary outcome measures were limb salvage and pain relief. The mean pain
      reduction in both treatment groups was 50% (from 5 to 2.5 on the visual analog
      scale). The 2-year limb survival was 52% (SCS) versus 46% (standard treatment; p
      = 0.47). The number of patients undergoing major amputations in the SCS group
      with intermediate TcpO2 values was half of that in the standard group (14 vs. 28;
      24 vs. 48%; p = 0.17). Implantation was successful in 51 patients. Technical
      problems such as loss of stimulation due to lead displacement occurred in 13
      patients (22%), local infection at the site of implantation occurred in 3
      patients (5%), resulting in a total complication rate of 27%. Premature depletion
      of the battery occurred within 2 years in 3 patients (5%). There were no lead
      fractures, epidural infections, hematoma or cerebrospinal fluid leakage. Training
      of physicians and better reliability of the hardware should reduce the frequency
      of technical problems. Lead displacement remains the major technical problem. The
      search for prognostic factors of limb salvage is important. One microcirculatory
      measurement (TcpO2) seems to have a prognostic value, which remains to be
      described more precisely.

PMID- 11251397
TI  - Thalamotomy caused by cardioversion in a patient treated with deep brain
      stimulation.
AB  - Deep brain stimulation (DBS) has been applied mainly for the treatment of
      intractable pain and involuntary movement disorders. Based on the rising numbers
      of patients undergoing DBS therapy, the possibility of emergent application of
      cardioversion for the treatment of occasional severe arrhythmia in DBS patients
      has also increased. However, there has been insufficient discussion about
      cardioversion in DBS patients. We employed a radiofrequency receiver that
      transmits to the brain impulses provided by an external generator through an
      antenna applied to the skin in front of the receiver. We experienced a patient
      who displayed almost complete cessation of his action tremor with thalamic
      stimulation. He also developed central dysesthetic pain and showed complete
      disappearance of his action tremor, even without stimulation, following
      successful application of cardioversion. It is considered that slight changes in
      the high-voltage electrical current or high-voltage electrical current spread
      induced central dysesthetic pain and almost identical effects to thalamotomy. We
      report for the first time a case of thalamotomy induced by cardioversion in a DBS
      patient. Clearly, we need to bear in mind that cardioversion has the capability
      to cause brain lesions in DBS patients with a radiofrequency receiver implanted
      subcutaneously at the anterior chest wall.

PMID- 11251399
TI  - Signal transduction mechanisms as new targets for allergists.

PMID- 11251398
TI  - In vivo proton magnetic resonance spectroscopy of brain tumors.
AB  - The ability of magnetic resonance spectroscopy (MRS) to differentiate neoplastic
      brain cells and their metabolic and structural characteristics is evaluated. We
      examined 120 patients with brain tumors using a 1.5-tesla MRI unit and MRS. The
      peak areas of N-acetyl-aspartate (NAA), phosphocreatine-creatine (Pcr-Cr),
      choline-containing compounds (Cho), lactate, lipids, myoinositol, amino acids and
      the ratios of NAA/Pcr-Cr, NAA/Cho and Cho/Pcr-Cr were calculated by a standard
      integral algorithm. In normal brain tissue, the following metabolites were
      identified: NAA at 2.0 ppm, Pcr-Cr at 3.0 ppm and Cho at 3.2 ppm. The different
      concentrations of the metabolites examined and their role in the biochemical
      profile of different types of tumors are discussed. The confidence interval of
      the MRS versus pathology was between 0.9 and 0.954, while it was between 0.52 and
      0.631 for MRI versus pathology. The Cho/Pcr-Cr ratio is a very important
      malignancy marker for histologic tumor grading of astrocytomas. The greater this
      ratio, the higher the grade of the astrocytoma. NAA/Pcr-Cr together with Cho/Pcr
      Cr help specify the presence or absence of a neoplasm. Proton MRS is a useful and
      promising diagnostic modality not only in diagnosing but also in grading solid
      brain tumors.

PMID- 11251400
TI  - Controlling allergic inflammation by signaling regulation of eosinophils.

PMID- 11251401
TI  - Allergy and sports.

PMID- 11251402
TI  - Involvement of urban living environments in atopy and enhanced eosinophil
      activity: potential risk factors of airway allergic symptoms.
AB  - BACKGROUND: Airway allergic diseases, such as bronchial asthma and allergic
      rhinitis, have increased, especially in urban areas. These diseases are
      characterized by airway inflammation with enhanced eosinophil activity, and the
      risk of disease development has been shown to increase with the prevalence of
      atopy. METHODS: Questionnaires were administered to 426 healthy adult women aged
      30-74 years, living in an urban area of Osaka, Japan, to survey individual living
      environments and airway allergic symptoms such as cough, sputum, and wheezing.
      Moreover, serum house-dust-mite (Dermatophagoides pteronyssinus, [Der p])
      specific immunoglobulin E (IgE) and serum eosinophil cationic protein (ECP) were
      examined by radioimmunoassay, and the atopic status (atopic sensitization) and
      enhanced eosinophil activity were assessed as Der p-specific IgE RAST scores of 2
      6 and ECP levels of more than 10 ng/ml, respectively. RESULTS: Intensive use of
      electric air conditioners in hot weather (odds ratio: 2.07 [95% CI: 1.11-3.87])
      and mold proliferation in the kitchen (2.77 [1.34-5.73]) significantly increased
      the risk of atopic sensitization. Poor home ventilation and family smoking
      appeared to be positively but not significantly associated with atopic
      sensitization. Personal smoking and intensive use of the air conditioner appeared
      to be positively related to enhanced eosinophil activity. Atopic status showed
      significant involvement in the development of wheezing, and the development of
      cough was significantly associated with enhanced eosinophil activity.
      CONCLUSIONS: The results suggest that some urban styles of living are involved in
      atopic sensitization and enhanced eosinophil activity in the Japanese urban
      population, probably due to living conditions, such as indoor dampness and poor
      home ventilation, caused by tight insulation, which increase exposure to indoor
      air pollutants, such as respirable mite allergens and tobacco smoke.

PMID- 11251403
TI  - Eosinophil cationic protein and specific IgE in serum and nasal mucosa of
      patients with grass-pollen-allergic rhinitis and asthma.
AB  - BACKGROUND: After allergen exposure, IgE-bearing mast cells surface in
      respiratory mucosa. Eosinophils are also recruited locally by chemotactic
      mediators; they are the main cell directly involved in the late phase of allergic
      inflammation. IgE antibody and eosinophil cationic protein (ECP) are routinely
      determined mainly in serum although they exert their pathogenetic role more
      directly on mucosal surfaces. METHODS: We performed a comparative study of IgE
      antibody to grass and ECP on nasal mucosa and blood samples in order to evaluate
      the relevance of monitoring allergic inflammation in the target organ. Thirty-one
      patients and 10 nonatopic controls were enrolled in the protocol. Twenty-six
      subjects allergic to grass, 11 with rhinitis (group 1) and 15 with asthma and
      rhinitis (group 2), completed the study. Five patients dropped out. Specific IgE
      to grass and ECP was determined in nasal mucosa by our method based on in situ
      incubation. RESULTS: Serum IgE to grass did not increase during the pollen peak,
      as did nasal IgE, in group 1 from before the pollen peak, from 2.3 to 3.2 kU/l
      (P=0.02), and in group 2 at the pollen peak, from 4.8 to 12.2 kU/l (P=0.01).
      Serum ECP did not show any significant variation in group 1, but it increased at
      pollen peak from 6 to 11.2 microg/l (P=0.01) in group 2. Nasal ECP increased
      significantly in both groups even before the pollen peak. In group 1, ECP values
      rose from 15 to 39.9 microg/l (P=0.01). In group 2, ECP increase was much higher
      than in group 1, from 9 to 213 microg/l (P=0.001). Serum eosinophils, like nasal
      ECP, showed a significant increase of values from before the pollen peak in both
      groups, without correlation with serum ECP in rhinitic patients. CONCLUSIONS:
      Both specific IgE and ECP in the nasal mucosa showed a better correlation with
      allergen exposure than serum evaluations. With an appropriate method, allergic
      inflammation may be best monitored in the nasal mucosa.

PMID- 11251404
TI  - Characterization of cross-reacting allergens in mango fruit.
AB  - BACKGROUND: Allergic reactions to mango fruit have become increasingly important.
      A cross-reaction between mango fruit, various other foods, and respiratory
      allergens has been assumed but not investigated until now. METHODS: The sera of
      nine patients were used to characterize cross-reacting allergens in mango fruits
      by EAST inhibition and immunoblot inhibition. RESULTS AND CONCLUSIONS: EAST
      inhibition and immunoblot inhibition demonstrated that cross-reactions between
      mango fruits, mugwort pollen, birch pollen, celery, and carrot are based on
      allergens related to Bet v 1 and Art v 1, the major allergens of birch and
      mugwort pollen, respectively.

PMID- 11251405
TI  - Receiver operating characteristics curve analysis of cutaneous skin test
      reactions to predict hay fever and asthma symptoms in the Normative Aging Study.
AB  - BACKGROUND: We used receiver operating characteristic (ROC) curves to determine
      optimal cutoff values and to evaluate the ability of ragweed, mixed grasses,
      mixed trees, and house-dust antigens to predict symptoms of hay fever and asthma.
      METHODS: Between 1984 and 1993, 1386 members of the Normative Aging Study cohort
      had at least one examination that included evaluation of cutaneous
      hypersensitivity to common aeroallergens by skin prick testing. Standard
      questionnaires based on the American Thoracic Society DLD-78 questionnaire
      obtained information on respiratory symptoms, illness, and smoking habits.
      RESULTS: Ragweed was the best univariate predictor for both hay fever and asthma
      symptoms: the area under the ROC curve for hay fever was 0.71 (95%) CI 0.67
      0.74); for asthma, it was 0.65 (95% CI 0.55-0.75). For hay fever, dichotomizing
      the average reaction to four antigens at 2 mm gave a sensitivity of 56% and a
      specificity of 83%; at 3 mm, the sensitivity was 38% and specificity 92%. For
      asthma, dichotomizing the skin test reaction at 2 mm gave a sensitivity ranging
      from 30% for reaction to mixed grasses to 56% for the ragweed antigen reaction.
      CONCLUSIONS: Although in this older population skin test reactivities did not
      predict current asthma symptoms with high sensitivity, our results support the
      use of cutoff values of 2 or 3 mm as commonly used in studies of hay fever
      symptoms.

PMID- 11251406
TI  - Anaphylaxis to mite-contaminated flour.

PMID- 11251407
TI  - IgE-mediated allergy to henna.

PMID- 11251408
TI  - Allergy to a tooth root devitalizing material.

PMID- 11251409
TI  - Allergy and contrast media.

PMID- 11251411
TI  - Clinical features of cashew allergy.

PMID- 11251410
TI  - Exhaled NO reduced on allergen avoidance.

PMID- 11251412
TI  - Widespread thromboembolism in allergy.

PMID- 11251413
TI  - CD124 on monocytes in grass-pollen allergy.

PMID- 11251414
TI  - Not one lancet for multiple SPT.

PMID- 11251416
TI  - Hypersensitivity to ASA.

PMID- 11251415
TI  - IgE-mediated allergy to bromelain.

PMID- 11251417
TI  - String bean-induced anaphylaxis.

PMID- 11251419
TI  - Exanthema to metamizole.

PMID- 11251418
TI  - Delayed hypersensitivity to cefotetan.

PMID- 11251420
TI  - Killing mites with heat.

PMID- 11251421
TI  - Anaphylactic reaction to formaldehyde.

PMID- 11251422
TI  - Allergic contact dermatitis from 2-butin-1,4-diol.

PMID- 11251423
TI  - Appraisal and revalidation need sensitive handling.

PMID- 11251424
TI  - The effect of nitrous oxide on the inhibition of somatosensory evoked potentials
      by sevoflurane in children.
AB  - Inhalational anaesthetics inhibit somatosensory evoked potentials. The present
      study examined the effect of nitrous oxide in anaesthetic mixture with
      sevoflurane on the somatosensory evoked potential in children. Forty-five
      patients aged between 6 months and 6 years undergoing club foot surgery were
      studied to verify the influence of sevoflurane alone (21 patients) and
      sevoflurane with nitrous oxide (24 patients) on the somatosensory evoked
      potential. Fractional inspired concentration of nitrous oxide and fractional end
      tidal (alveolar) sevoflurane were measured to estimate the multiples and
      submultiples of the minimal alveolar concentration (age corrected). The
      somatosensory evoked potential signals were obtained by stimulation of the median
      nerve. Nitrous oxide (FI = 0.63 +/- 2.5) with sevoflurane caused more reduction
      in the amplitude of somatosensory evoked potential waves and a greater increase
      in the latency of somatosensory evoked potential waves in comparison with
      sevoflurane alone. The results show that it is possible to obtain the inhibition
      of somatosensory evoked potential with smaller concentrations of sevoflurane,
      when it is used with nitrous oxide.

PMID- 11251425
TI  - Variations in expenditure between adult general intensive care units in the UK.
AB  - This paper presents the findings from the second pilot study of the cost block
      method in 21 adult general intensive care units (ICUs). The aim of this study was
      to explore the possible reasons for the variation in cost identified in a
      previous pilot study of 11 ICUs. Data were collected for the six cost blocks for
      the financial year 1996/97. Multivariate analysis showed that 93% of the
      variation in expenditure on disposable equipment could be explained by the number
      of ICU beds, the number of admissions and the presence of a high-dependency unit
      (HDU). Ninety-two per cent of the variation in nursing staff expenditure was
      explained by the number of ICU beds and the presence of an HDU. Hospital type and
      the number of patient days explained 76% of the variation in expenditure on
      consultant staff. Sixty-four per cent of the variation in drug and fluid
      expenditure was explained by the number of patient days.

PMID- 11251426
TI  - Intra-operative blood salvage in abdominal trauma: a review of 5 years'
      experience.
AB  - We performed a retrospective audit of 1235 patients presenting between 1992 and
      1997, following the introduction of intra-operative blood salvage at our
      hospital. Twenty-two cases of severe abdominal trauma requiring emergency
      laparotomy and intra-operative blood salvage were identified. The impact of intra
      operative blood salvage in aiding resuscitation and reducing demand on allogeneic
      blood supplies is discussed.

PMID- 11251427
TI  - Tracheal intubation and cervical spine excursion: direct laryngoscopy vs.
      intubating laryngeal mask.
AB  - Until recently, the most appropriate technique of intubating a patient with a
      cervical spine injury has been the subject of debate. Tracheal intubation by
      means of the intubating laryngeal mask (Fastrach), a modified conventional
      laryngeal mask airway, seems to require less neck manipulation. The aim of this
      study was to compare the excursion of the upper cervical spine during tracheal
      intubation using direct laryngoscopy with that during intubation via the
      laryngeal mask (Fastrach), by examination of lateral cervical spine radiographs
      in healthy young patients. The intubating laryngeal mask (Fastrach) caused less
      extension (at C1-2 and C2-3) than intubation by direct laryngoscopy. Direct
      laryngoscopy is still the fastest method to secure an airway provided no
      intubating difficulties are present. However, in trauma patients requiring rapid
      sequence induction and in whom cervical spine movement is limited or undesirable,
      the intubating laryngeal mask (Fastrach) is a safe and fast method by which to
      secure the airway.

PMID- 11251428
TI  - Historical note: Snow, Empson and the Barkers of Bath.
AB  - The identity of the artist who painted the well-known portrait of John Snow has
      been established. It has been discovered that the painting was exhibited at the
      Royal Academy of Arts, London in 1847.

PMID- 11251429
TI  - Retention of airborne latex particles by a bacterial and viral filter used in
      anaesthesia apparatus.
AB  - We have developed a series of laboratory tests to evaluate the efficiency of a
      heat and moisture exchanger filter (Pall BB25) in retaining latex particles in
      order to protect allergic patients during anaesthesia. Latex particles were
      nebulised with cornstarch as a support and collected for assay in a flask, with
      or without the filter integrated into the experimental circuit. With the Pall
      BB25 filter in the circuit, no natural latex proteins were detected by
      measurement of either total protein or antigenic latex proteins. The Pall BB25
      filter may represent a useful means of preventing inhalation of latex particles
      during anaesthesia in susceptible patients.

PMID- 11251430
TI  - Non-invasive ventilation in the treatment of ventilatory failure following
      corrective spinal surgery.
AB  - Non-invasive positive pressure ventilation has previously been used successfully
      to treat both acute and chronic ventilatory failure secondary to a number of
      conditions, including scoliosis. We report two patients in whom it was used, on
      three separate occasions, to treat acute ventilatory failure following corrective
      spinal surgery. Non-invasive positive pressure ventilation may be useful
      postoperatively in high-risk patients undergoing major spinal surgery in an
      attempt to prevent intubation and its attendant complications.

PMID- 11251431
TI  - Damage to the conus medullaris following spinal anaesthesia.
AB  - Seven cases are described in which neurological damage followed spinal or
      combined spinal-epidural anaesthesia using an atraumatic spinal needle. All
      patients were women, six obstetric and one surgical. All experienced pain during
      insertion of the needle, which was usually believed to be introduced at the L2-3
      interspace. In all cases, there was free flow of cerebrospinal fluid before
      spinal injection. There was one patchy block but, in the rest, anaesthesia was
      successful. Unilateral sensory loss at the levels of L4-S1 (and sometimes pain)
      persisted in all patients; there was foot drop in six and urinary symptoms in
      three. Magnetic resonance imaging showed a spinal cord of normal length with a
      syrinx in the conus (n = 6) on the same side as both the persisting clinical
      deficit and the symptoms that had occurred at insertion of the needle. The tip of
      the conus usually lies at L1-2, although it may extend further. Tuffier's line is
      an unreliable method of identifying the lumbar interspaces, and anaesthetists
      commonly select a space that is one or more segments higher than they assume.
      Because of these sources of error, anaesthetists need to relearn the rule that a
      spinal needle should not be inserted above L3.

PMID- 11251432
TI  - Reversing sevoflurane-associated Q-Tc prolongation by changing to propofol.
AB  - Congenital or acquired forms of the long Q-T syndrome may result in ventricular
      tachycardia known as torsade de pointes. Many drugs including volatile
      anaesthetics modify the Q-T interval. Sevoflurane is known to prolong of the rate
      corrected Q-T interval (Q-Tc). The objective of this study was to determine
      whether the sevoflurane-associated Q-Tc prolongation is rapidly reversible when
      propofol is substituted for sevoflurane. Thirty-two female patients were
      allocated to two groups. All patients received sevoflurane induction and
      anaesthesia for 15 min. In one group, sevoflurane was then discontinued and
      anaesthesia maintained on propofol for another 15 min. The second group received
      sevoflurane anaesthesia for 30 min. Measurements were taken before, and 15, 20,
      25 and 30 min after induction. Q-Tc prolongation was significantly reduced 5, 10
      and 15 min after propofol had been substituted for sevoflurane. We conclude that
      the sevoflurane-associated Q-Tc prolongation is fully reversible within 15 min
      when propofol is substituted for sevoflurane.

PMID- 11251433
TI  - Induction with propofol target-concentration infusion vs. 8% sevoflurane
      inhalation and alfentanil in hypertensive patients.
AB  - Haemodynamic parameters during an inhalation induction with 8% sevoflurane were
      compared with those obtained with a target-controlled infusion of propofol in 50
      hypertensive patients in a prospective randomised study. Heart rate and arterial
      pressure were recorded continuously. End-tidal sevoflurane and nitrous oxide
      concentration, SpO2 and bispectral index (BIS) were also collected from the
      beginning of anaesthesia until 8 min after tracheal intubation. Patients either
      received 4 mg.l-1 target-concentration propofol or performed a vital capacity
      inhalation of 8% sevoflurane in a high flow of oxygen (8 l.min-1) supplemented
      with 50% nitrous oxide at loss of consciousness. As soon as BIS was < 60, 20
      microg.kg-1 alfentanil and 0.6 mg.kg-1 rocuronium were injected and orotracheal
      intubation was then performed 1 min later. Thereafter, the end-tidal
      concentration of sevoflurane was reduced to 1.3 minimum alveolar concentration
      (MAC). Hypotension was defined as a 30% decrease in arterial pressure and was
      treated with repeated 3-mg boluses of ephedrine. When 12 mg ephedrine was unable
      to correct hypotension, the concentration of propofol was reduced by 1 mg.l-1 and
      that of sevoflurane by 0.5%. Hypotension occurred in 22 patients in the
      sevoflurane group and 21 in the propofol group, and hypertension occurred in two
      and three patients in each group, respectively. The maximal reduction in mean
      (SD) arterial pressure was similar in the sevoflurane (45 (4) mmHg) and propofol
      (41.3 (2.6) mmHg) groups, as were the ephedrine requirements (9.6 (1.1) vs. 9.1
      (1.1) mg, sevoflurane vs. propofol, p > 0.05), the duration of hypotension (276
      (37) vs. 292 (38) s, sevoflurane vs. propofol, p > 0.05), and the number of
      hypotensive episodes or anaesthetic changes and depth of anaesthesia.
      Nevertheless, heart rate was lower during the 8 min following tracheal intubation
      in the sevoflurane group. In both groups, the duration of hypotension was easily
      controlled either by ephedrine or by adjusting the anaesthetic concentrations.
      Overall, haemodynamic tolerance appears to be similar in the two techniques.
      Because hypotension occurred after alfentanil in most patients, this study
      questioned which is the best opioid dose, if any, to associate with propofol or
      sevoflurane for the induction in hypertensive patients.

PMID- 11251434
TI  - Identifying the more patent nostril before nasotracheal intubation.
AB  - We have studied the reliability of two simple pre-induction tests used to select
      the more patent nostril for nasotracheal intubation by comparing their results
      with those obtained from fibreoptic examination of the nostrils, in 75 maxillo
      facial patients requiring nasotracheal intubation under general anaesthesia, who
      had no history of nasal obstruction. The tests comprised (1) estimation of the
      rate of airflow through each nostril during expiration by palpating the passage
      of air when the contralateral nostril was occluded, and (2) asking for the
      patient's assessment of airflow through the nostrils, following the
      administration of a vasoconstrictor. After each test, noses were classified as
      left or right nostril clearer or nostrils equally clear. After the induction of
      general anaesthesia, bilateral nasendoscopies were performed and videotape
      recordings of these were later analysed by an otolaryngologist who had no
      knowledge of the test results. Intranasal abnormalities were identified and noses
      were again classified as left or right nostril clearer or nostrils equally clear.
      There was no significant difference between the overall diagnostic success rates
      of the two tests (44% and 47%, respectively). In patients with intranasal
      abnormalities, the numbers of correct diagnoses made by the two tests were not
      significantly different and were also not significantly different from the number
      of correct selections made if only the right nostril or only the left nostril had
      been used for the intubation. In view of the relatively high diagnostic failure
      rates, anaesthetists should not rely on the two tests investigated when selecting
      the best nostril for nasotracheal intubation.

PMID- 11251435
TI  - Hip flexion and lumbar puncture: a radiological study.
AB  - When lumbar puncture is performed in the sitting position, the patient's thighs
      are usually at an angle of approximately 90 degrees to the trunk, whereas in the
      lateral position, hip flexion is employed by flexing the patient's knees to the
      chest. We measured the presumed but hitherto unquantified widening of lumbar
      interspinous spaces resulting from hip flexion. Lumbar spine lateral radiographs
      were taken in volunteers in the sitting position with and without hip flexion,
      and interspinous space width was measured and compared. Mean lumbar interspinous
      space width at L2-3, L3-4 and L4-5 increased by 7%, 11% and 21%, respectively,
      with the hips flexed. Hip flexion in the sitting position will anatomically
      optimise lumbar interspinous space width for needle passage, and statistically
      significant increases in space width have been demonstrated increasing
      progressively from L2-3 to L4-5.

PMID- 11251436
TI  - Cardiovascular effects of intravenous propofol administered at two infusion
      rates: a transthoracic echocardiographic study.
AB  - We assessed the haemodynamic changes after a propofol infusion at two rates in
      low-risk unpremedicated patients (ASA I-II). To determine contractility changes
      and loading conditions, we measured the ejection fraction, end-systolic quotient
      and fractional shortening on transthoracic echocardiograms. We studied 40
      patients undergoing peripheral neurosurgical procedures under general anaesthesia
      induced by propofol alone (total dose 2.5 mg.kg-1). Patients were randomly
      assigned to receive propofol at an infusion rate of 10 mg.s-1; or 2 mg.s-1.
      Haemodynamic data were recorded simultaneously immediately before propofol
      infusion, at the end of infusion, and 5 and 10 min after the infusion ended. The
      higher infusion rate induced a larger decrease in mean arterial pressure than the
      lower infusion rate (- 20% vs. - 10% from baseline, p = 0.01). In both groups,
      global and segmental ventricular function remained unchanged throughout the
      study. In both groups, there were markedly reduced end-systolic quotients-
      presumably related to diminished afterload, and in the higher infusion-rate group
      a significant reduction in fractional shortening--presumably related principally
      to diminished preload.

PMID- 11251437
TI  - The role of the anaesthetist: replacement brain.

PMID- 11251438
TI  - Anaesthesia, what's in a name?

PMID- 11251439
TI  - Complete power failure 1.

PMID- 11251440
TI  - Complete power failure 2.

PMID- 11251441
TI  - The Combitube should be redesigned for anaesthetic use.

PMID- 11251442
TI  - Supplementary oxygenation with the laryngeal mask airway 1.

PMID- 11251443
TI  - Supplementary oxygen with the laryngeal mask airway 2.

PMID- 11251444
TI  - The self-regulating bag.

PMID- 11251445
TI  - A new device to facilitate awake oral fibreoptic intubation.

PMID- 11251446
TI  - Herniation of tracheal tube cuffs: a simple teaching model.

PMID- 11251447
TI  - Transparent obstruction of RAE tube.

PMID- 11251449
TI  - Administering ambient pressure oxygenation to the non-ventilated lung during
      thoracoscopic surgery.

PMID- 11251450
TI  - Light wand guided tracheal intubation through the intubating laryngeal mask.

PMID- 11251452
TI  - Full circle.

PMID- 11251453
TI  - Anterior deviation of the trachea.

PMID- 11251454
TI  - Mishaps with a central venous cannula in the ICU.

PMID- 11251455
TI  - Aortic cross-clamping in sickle cell disease.

PMID- 11251456
TI  - Close loop anaesthesia using bispectral index.

PMID- 11251458
TI  - Are peri-operative peripheral nerve lesions preventable?

PMID- 11251460
TI  - Peripheral nerve injuries.

PMID- 11251461
TI  - Spinal cord damage.

PMID- 11251462
TI  - Epidural failures and trainees' performance.

PMID- 11251464
TI  - Should epidurals be avoided in acupunctured patients?

PMID- 11251465
TI  - Total upper eyelid drop as an endpoint marker of peribulbar anaesthesia.

PMID- 11251467
TI  - Anaesthetic menu: a step too far?

PMID- 11251469
TI  - Physical incompatibility between atracurium and intravenous diclofenac.

PMID- 11251470
TI  - Incidence of anaphylaxis under anaesthesia.

PMID- 11251471
TI  - How should we manage the electronically tagged patient?

PMID- 11251472
TI  - An unusual method of diagnosing postoperative sore throat.

PMID- 11251473
TI  - Artificial organs and vanishing boundaries.
AB  - With the first clinical use of the artificial kidney over 5 decades ago, we
      entered into a new era of medicine-that of substitutive and replacement therapy.
      Yet it took nearly another 15 years until chronic treatment was possible and
      nearly another 15 years until widespread treatment was possible due to government
      support. The history of development and clinical use of other artificial organ
      technologies such as the artificial heart and heart valves, the artificial lung,
      artificial blood, joint replacements, the artificial liver, the artificial
      pancreas, immunologic, metabolic, and neurologic support, neurocontrol, and
      tissue substitutes have followed similar long development paths. Despite their
      relatively long time to be put into clinical use, the contributions of artificial
      organ technologies to the betterment of mankind have been unquestionably a major
      success. For example, modern day surgery would not be possible without heart-lung
      support, and the technologies for heart support have led to the development of
      various minimally invasive technologies. The powerful impact that artificial
      organ technologies presently has on our lives is seen through the statistic that
      in the U.S.A. nearly 1 in 10 persons is living with an implanted medical device.
      With the aging of our population and the improvements in technologies, these
      numbers will only increase.

PMID- 11251474
TI  - Fluid volumes determination by impedance spectroscopy and hematocrit monitoring:
      application to pediatric hemodialysis.
AB  - A method for extracting fluid volumes from multifrequency bioimpedance, which
      takes into account the body geometry and the presence of nonconducting elements,
      was tested on 12 young dialyzed patients against correlations for total body
      water volumes (TBW) from Watson et al. and Humes et al. Our calculations of TBW
      from impedance were found to overestimate Humes' values by 0.25 L (0.8%)
      postdialysis and by 2.08 L (6.5%) predialysis. Extracellular water (ECW) was
      found to contribute an average of 93% of ultrafiltered volume. Intracellular
      water volume (ICW) determination from impedance was found to be too imprecise to
      predict its variation during dialysis; therefore, ICW variations were calculated
      as the difference between ultrafiltration and ECW changes. The continuous
      recording of hematocrit by an optical device monitored changes in plasma and
      interstitial volumes. In most cases, ultrafiltration was compensated mainly by a
      contribution from interstitial fluid, and the drop in plasma volume was generally
      moderate.

PMID- 11251475
TI  - Better correction of metabolic acidosis, blood pressure control, and phagocytosis
      with bicarbonate compared to lactate solution in acute peritoneal dialysis.
AB  - Lactate solution has been the standard dialysate fluid for a long time. However,
      it tends to convert back into lactic acid in poor tissue-perfusion states. The
      aim of this study was to evaluate the efficacy of magnesium (Mg)- and calcium
      (Ca)-free bicarbonate solution compared with lactate solution in acute peritoneal
      dialysis (PD). Renal failure patients who were indicated for dialysis and needed
      acute PD were classified as shock and nonshock groups, and then were randomized
      to receive either bicarbonate or lactate solution. Twenty patients were enrolled
      in this study (5 in each subgroup). In the shock group, there were more rapid
      improvements and significantly higher levels of blood pH (7.40 +/- 0.04 versus
      7.28 +/- 0.05, p < 0.05), serum bicarbonate (23.30 +/- 1.46 versus 18.37 +/- 1.25
      mmol/L, p < 0.05), systolic pressure (106.80 +/- 3.68 versus 97.44 +/- 3.94 mm
      Hg, p < 0.05), mean arterial pressure (80.72 +/- 2.01 versus 73.28 +/- 2.41 mm
      Hg, p < 0.05), percentages of phagocytosis of circulating leukocytes (65.85% +/-
      2.22 versus 52.12% +/- 2.71, p < 0.05), and percentages of positive nitroblue
      tetrazolium (NBT) reduction test without and with stimulation (14.43 +/- 1.93
      versus 9.43 +/- 2.12, p < 0.05 and 65.08 +/- 6.80 versus 50.23 +/- 4.21, p <
      0.05, respectively) in the bicarbonate subgroup compared with the lactate
      subgroup. In the nonshock group, blood pH, serum bicarbonate, and phagocytosis
      assays in both subgroups were comparable. Lactic acidosis was more rapidly
      recovered and was significantly lower with bicarbonate solution for both shock
      and nonshock groups (3.63 +/- 0.37 versus 5.21 +/- 0.30 mmol/L, p < 0.05 and 2.92
      +/- 0.40 versus 3.44 +/- 0.34 mmol/L, p < 0.05, respectively). Peritoneal urea
      and creatinine clearances in both subgroups were comparable for both shock and
      nonshock groups. There was no peritonitis observed during the study. Serum Mg and
      Ca levels in the bicarbonate subgroup were significantly lower, but no clinical
      and electrocardiographic abnormality were observed. We concluded that Mg- and Ca
      free bicarbonate solution could be safely used and had better outcomes in
      correction of metabolic acidosis, blood pressure control, and nonspecific
      systemic host defense with comparable efficacy when compared to lactate solution.
      It should be the dialysate of choice for acute PD especially in the poor tissue
      perfusion states such as shock, lactic acidosis, and multiple organ failure.

PMID- 11251476
TI  - Multisorbent plasma perfusion in fulminant hepatic failure: effects of duration
      and frequency of treatment in rats with grade III hepatic coma.
AB  - Using the model of galactosamine-induced fulminant hepatic failure in the rat,
      the effects of multisorbent plasma perfusion over Asahi uncoated spherical
      charcoal, Plasorba (BR-350) resin, and an endotoxin removing adsorbent (polymyxin
      B-sepharose) were determined in Grade III hepatic coma animals by studying
      survival as influenced by timing, duration, and frequency of treatment. The
      effects of treatment on liver cell proliferation and endotoxin removal also were
      examined. The results demonstrate that duration and frequency of treatment are
      major contributing factors in the successful application of nonbiological
      membrane-based multisorbent liver support systems. Examination of the
      regenerative activity in the liver indicates an enhanced proliferative response
      following multisorbent plasma perfusion compared with untreated fulminant hepatic
      failure (FHF) paired controls. Utilizing an endotoxin removal adsorbent alone, a
      marked reduction in systemic levels of endotoxin in FHF was demonstrated compared
      with nonperfused FHF paired controls. Despite current emphasis on bioartificial
      liver support systems, plasma purification by multisorbent systems offers a
      simple method for the removal of circulating toxic metabolites in general
      together with specific toxin removal.

PMID- 11251477
TI  - Oxygen transfer in a convection-enhanced hollow fiber bioartificial liver.
AB  - A mathematical model was developed to predict oxygen transport in a hollow fiber
      bioartificial liver device. The model parameters were taken from the HepatAssist
      2000 device, a plasma perfused hollow fiber cartridge with primary hepatocytes
      seeded in the extracapillary space. Cellular oxygen uptake was based on Michaelis
      Menten kinetics. Oxygen transport due to the convective flow of plasma into the
      extracapillary space was considered. The effect of modulating several important
      parameters was investigated, namely, the Michaelis-Menten constant V(m) (the
      maximum oxygen consumption per unit volume of the cell mass), the oxygen partial
      pressure, the flow rate of the plasma at device inlet, and the permeability of
      the cell mass contained in the extracapillary space. A computer implementation of
      the model was used to assess whether a given number of cells could be maintained
      within such a device. The results suggest that a substantial proportion of the
      hepatocytes are exposed to hypoxic conditions under which metabolism may be
      impaired.

PMID- 11251478
TI  - Microencapsulated bovine chromaffin cell xenografts into hemiparkinsonian rats: a
      drug-induced rotational behavior and histological changes analysis.
AB  - Bovine chromaffin cells were microencapsulated within alginate-polylysine
      alginate (APA) membranes. Microencapsulated bovine chromaffin cells as well as
      unencapsulated cells and empty microcapsules were grafted into the brain of
      hemiparkinsonian rats with 6-hydroxydopamine (6-OHDA) lesions. Apomorphine
      induced rotational behavior of the host animals and the survival of the grafted
      chromaffin cells were examined after transplantation. The animals receiving
      microencapsulated bovine chromaffin cells showed a significant decrease (17.6-
      35.6%) in apomorphine-induced rotation 1 week postimplantation that remained
      stable for the 10 month test period. Fluorescent histochemistry further revealed
      that microencapsulation increased the chromaffin cell survival with only a
      minimum host reaction for up to 10 months posttransplantation while the survival
      of free, unencapsulated chromaffin cells was only modest and was accompanied by a
      large inflammatory response. The reduction of apomorphine-induced rotations was
      correlated with the survival of bovine chromaffin cells in the host brain. The
      data indicate that encapsulation of bovine chromaffin cells in APA membranes
      reduces the host immune response to the xenograft and prolongs the viability of
      the grafted cells.

PMID- 11251479
TI  - Integrating particle image velocimetry and laser Doppler velocimetry measurements
      of the regurgitant flow field past mechanical heart valves.
AB  - This study investigates the transient regurgitant flow downstream of a prosthetic
      heart valve using both laser Doppler velocimetry (LDV) and particle image
      velocimetry (PIV). Until now, LDV has been the more commonly used tool in
      investigating the flow characteristics associated with mechanical heart valves.
      The LDV technique allows point-by-point velocity measurements and provides enough
      information about the temporal variations in the flow. The main drawback of this
      technique is the time consuming nature of the data acquisition process in order
      to assess an entire flow field area. The PIV technique, on the other hand, allows
      measurement of the entire flow field in space in a plane at a given instant. In
      this study, PIV with spatial resolution of 0 (1 mm) and LDV with a temporal
      resolution of 0 (1 ms) were used to measure the regurgitant flow proximal to the
      Bjork-Shiley monostrut (BSM) valve in the mitral position. With PIV, the ability
      to measure 2 velocity components over an entire plane simultaneously provides a
      very different insight into the flow field compared to a more traditional point
      to-point technique like LDV. In this study, a picture of the effects of occluder
      motion on the fluid flow in the atrial chamber is interpreted using an
      integration of PIV and LDV measurements. Specifically, fluid velocities in excess
      of 3.0 m/s were recorded in the pressure-driven jet during valve closure, and a
      1.5 m/s sustained regurgitant jet was observed on the minor orifice side.
      Additionally, the effects of the impact and subsequent rebound of the occluder on
      the flow also were clearly recorded in spatial and temporal detail by the PIV and
      LDV measurements, respectively. The PIV results provide a visually intuitive way
      of interpreting the flow while the LDV data explore the temporal variations and
      trends in detail. This analysis is an integrated flow description of the effects
      of valve closure and leakage on the pulsatile regurgitation flow field past a
      tilting-disc mechanical heart valve (MHV). It further reinforces the hypothesis
      that the planar flow visualization techniques, when integrated with traditional
      point-to point techniques, provide significantly more insight into the complex
      pulsatile flow past MHVs.

PMID- 11251480
TI  - Effect of variation in systemic blood flow on plasma TNF-alpha in a pig model
      with left ventricular assist device.
AB  - Tumor necrosis factor-alpha (TNF-alpha) release has been implicated in a sepsis
      like syndrome following cardiopulmonary bypass (CPB). This also may be important
      in patients who have had a left ventricular assist device (LVAD) implanted. This
      report investigates the effect of reducing systemic blood flow on hemodynamic
      response, mixed venous oxygen saturation (SvO(2)), and the release of TNF-alpha.
      LVADs were implanted in 9 pigs. The aorta was clamped, and thus the LVAD flow
      represented the entire systemic blood flow. Plasma TNF-alpha in the femoral
      artery (FA) and superior mesenteric vein (SMV) was measured at baseline and
      following systemic blood flow changes. Simultaneously, hemodynamic parameters and
      oxygen saturation in the pulmonary artery (SvO(2)) were measured. Following
      reductions in systemic blood flow, plasma TNF-alpha increased gradually to a
      maximum level at a systemic blood flow of 20%. There was no significant
      difference between TNF-alpha levels in the SMV and the FA. There was a
      significant (p < 0.05) correlation between cardiac index, stroke volume index,
      and TNF-alpha. The SvO(2) decreased significantly (p < 0.05) at a systemic blood
      flow of 30 and 20%. A rise in TNF-alpha occurred when the SvO(2) was less than
      75%. The data demonstrate that a reduction in systemic blood flow causes an
      increase in plasma TNF-alpha. This can lead to the development of a sepsis-like
      syndrome in a group of patients who already are hemodynamically compromised.
      While weaning short-term LVAD support, rapid diminution of the cardiac output and
      the pump flow must be avoided.

PMID- 11251481
TI  - Automatic detection and classification of abnormalities for artificial hearts
      using a hierarchical self-organizing map.
AB  - A hierarchical self-organizing map (SOM) has been developed for automatic
      detection and classification of abnormalities for artificial hearts. The
      hierarchical SOM has been applied to the monitoring and analysis of an aortic
      pressure (AoP) signal measured from an adult goat equipped with a total
      artificial heart. The architecture of the network actually consists of 2
      different SOMs. The first SOM clusters the AoP beat patterns in an unsupervised
      way. Afterward, the outputs of the first SOM combined with the original time
      domain features of beat-to-beat data are fed to the second SOM for final
      classification. Each input vector of the second SOM is associated with a class
      vector. This class vector is assigned to every node in the second map as an
      output weight and learned according to Kohonen's learning rule. Some experimental
      results revealed that a certain abnormality caused by breakage of sensors could
      be identified and detected correctly and that the change in the state of the
      circulatory system could be recognized and predicted to some extent.

PMID- 11251484
TI  - Cesarean delivery in Shantou, China: a retrospective analysis of 1922 women.
AB  - BACKGROUND: In China the cesarean section rate increased significantly during the
      past four decades. This study examined the frequency and indications of cesarean
      birth in Shantou, a southern city in China. METHODS: An analysis was conducted of
      the medical records of 1922 women who had cesarean deliveries at Shantou City 2nd
      People's Hospital between January 1990 and December 1997. The medical records of
      10,490 women who gave birth during this period were examined. RESULTS: The
      average rate of cesarean delivery during the 8-year period was 19.4 +/- 2.3
      percent (means +/- standard error). From 1990 to 1997 the cesarean delivery rates
      ranged from 11.05 to 29.9 percent, respectively, although during this period the
      total annual number of deliveries decreased significantly from 1683 to 951. The
      rates of the most common indications per 100 women for cesarean delivery were
      failure to progress (23%), premature rupture of membranes (20%), fetal distress
      (19.4%), breech presentation (18.1%), uterine scar (14.6%), and prolonged
      pregnancy (11.3%). CONCLUSION: The cesarean delivery rate in Shantou, China, has
      increased steadily and significantly between 1990 and 1997, despite a decrease in
      the total number of births during the same period. This study showed that on an
      individual basis vaginal delivery was often possible and reduction of the
      cesarean delivery rate could be achieved safely by paying greater heed to
      appropriate indications.

PMID- 11251483
TI  - Is it necessary to suture all lacerations after a vaginal delivery?
AB  - BACKGROUND: Midwives tend to leave minor perineal lacerations to heal
      spontaneously, and clinical experience and studies show that women can suffer
      from their stitched lacerations. The study purpose was to determine any
      differences in the healing process and experience of minor perineal lacerations
      when they were sutured or not sutured. METHODS: Eighty term pregnant primiparas
      with minor perineal lacerations of grades I-II were randomized after childbirth.
      The experimental group was nonsutured and the control group was sutured. A follow
      up examination was performed at 2 to 3 days, 8 weeks, and 6 months after the
      delivery. Participants were asked about the type of discomfort, and the effect of
      the laceration on breastfeeding and sexual intercourse. RESULTS: No significant
      differences were found in the healing process. The type of pain differed between
      the groups, but the amount of discomfort was the same. The sutured group had to
      visit the midwife more often because of discomfort from the stitches. Sixteen
      percent of the women in the sutured group, but none in the nonsutured group (p =
      0.0385), considered that the laceration had had a negative influence on
      breastfeeding. CONCLUSIONS: Minor perineal lacerations can be left to heal
      spontaneously. The benefits for the woman include the possibility of having a
      choice, avoiding the discomfort of anesthesia and suturing, providing positive
      affects on breastfeeding.

PMID- 11251485
TI  - Breastfeeding duration in a multiethnic population in Hawaii.
AB  - BACKGROUND: The increasing ethnic diversity in the United States necessitates a
      study of variations in infant feeding patterns among ethnic groups. This study
      was conducted as part of Hawaii's surveillance system to identify infant feeding
      patterns in Hawaii; specifically, to identify factors influencing duration of
      breastfeeding among ethnically diverse mothers. METHODS: All women who delivered
      an infant in Hawaii between January 1 and March 31, 1989, were mailed surveys 14
      to 19 months after delivery. Fifty-one percent (n = 2011) of women responded, of
      whom 1574 (78%) did some breastfeeding and are included in the analysis of
      prediction of weaning (cessation of breastfeeding). Cox regression (survival)
      analysis was used to predict weaning. RESULTS: The median duration of
      breastfeeding was 150 days; 45 percent of infants were still breastfeeding at age
      6 months and 16 percent at age 1 year. Factors associated with early weaning were
      Japanese ethnicity; mother born in a country other than the United States, Japan,
      or the Philippines; first language other than English, or two languages at home;
      employed full-time outside the home; introduced formula or fruit before age 6
      months; received formula from the WIC program; and stopped breastfeeding for
      convenience, breast problems, problems getting breastfeeding started,
      insufficient milk, baby refusing the breast, and a sick baby. Factors associated
      with late weaning were older maternal age; college education; living on a rural
      island; previous breastfeeding experience; helpful breastfeeding advice from
      family or friends; receiving WIC for breastfeeding mothers; introducing the cup
      before age 6 months; and not giving fruit to the baby. CONCLUSION: In Hawaii,
      programs that address how and when to introduce foods, use of formula, and
      management of outside employment and breastfeeding should be made available to
      those groups of women at risk for early weaning to lengthen their duration of
      breastfeeding.

PMID- 11251487
TI  - Commentary: assessing women's well-being and social and emotional needs in
      pregnancy and the postpartum period.

PMID- 11251486
TI  - Measuring social support in pregnancy: can it be simple and meaningful?
AB  - BACKGROUND: It is important to determine the level of a woman's social support at
      the booking-in interview for prenatal care, but measurement tends to be ad hoc
      and nonquantifiable. The purpose of this study was to describe the Maternity
      Social Support Scale and the relationship between support scale ratings and the
      Edinburgh Postnatal Depression Scale and other health and service use outcomes.
      METHODS: Women (n = 901) who attended the antenatal clinic at the Royal Women's
      Hospital in Brisbane, Australia, were asked to complete a support scale as part
      of their booking-in interview. Participants were contacted at 16 weeks postpartum
      and invited to complete a follow-up questionnaire. Relationships between the
      scale and study outcomes were explored using analysis of variance and chi-square
      tests. RESULTS: Women with low social support in pregnancy were more likely than
      well-supported women to report poorer health during pregnancy (p = 0.006) and
      postnatally (p < 0.001), to book later for prenatal care (p = 0.000), to seek
      medical help more frequently (p = 0.004), and to be more depressed postnatally (p
      = 0.0001). CONCLUSION: Social support during pregnancy can be measured in a
      meaningful and simple way through the use of a short questionnaire administered
      at the prenatal booking-in visit.

PMID- 11251488
TI  - Childbirth and the development of acute trauma symptoms: incidence and
      contributing factors.
AB  - BACKGROUND: Little is known about the relationship between women's birthing
      experiences and the development of trauma symptoms. This study aimed to determine
      the incidence of acute trauma symptoms and posttraumatic stress disorder in women
      as a result of their labor and birth experiences, and to identify factors that
      contributed to the women's psychological distress. METHOD: Using a prospective,
      longitudinal design, women in their last trimester of pregnancy were recruited
      from four public hospital antenatal clinics. Telephone interviews with 499
      participants were conducted at 4 to 6 weeks postpartum to explore the medical and
      midwifery management of the birth, perceptions of intrapartum care, and the
      presence of trauma symptoms. RESULTS: One in three women (33%) identified a
      traumatic birthing event and reported the presence of at least three trauma
      symptoms. Twenty-eight women (5.6%) met DSM-IV criteria for acute posttraumatic
      stress disorder. Antenatal variables did not contribute to the development of
      acute or chronic trauma symptoms. The level of obstetric intervention experienced
      during childbirth (beta = 0.351, p < 0.0001) and the perception of inadequate
      intrapartum care (beta = 0.319, p < 0.0001) during labor were consistently
      associated with the development of acute trauma symptoms. CONCLUSIONS:
      Posttraumatic stress disorder after childbirth is a poorly recognized phenomenon.
      Women who experienced both a high level of obstetric intervention and
      dissatisfaction with their intrapartum care were more likely to develop trauma
      symptoms than women who received a high level of obstetric intervention or women
      who perceived their care to be inadequate. These findings should prompt a serious
      review of intrusive obstetric intervention during labor and delivery, and the
      care provided to birthing women.

PMID- 11251489
TI  - Partner support and pregnancy wantedness.
AB  - BACKGROUND: Women who experience unwanted pregnancy are at a greater risk of
      complicated pregnancy outcomes, and their children are more likely to experience
      physical or psychological problems in infancy, than those women with wanted
      pregnancies. The objective of this research was to explain the impact of a
      partner on women's decisions to want or not want their pregnancies. METHODS: A
      primary study subsample of 349 clinical interviews of pregnant women comprised
      the quantitative portion of the analysis, with a secondary study subsample of 20
      in-depth qualitative interviews of pregnant women complementing the statistical
      findings. Both samples included adult women (at least age 20 yr) of different
      ethnic groups who received Medicaid for their pregnancies and were in their first
      or early second trimester of pregnancy. Chi-square, t tests, and logistic
      regression were used for statistical analyses. RESULTS: A partner's stability,
      status, feelings toward pregnancy, and level of dependability and support all had
      a significant influence on women's experiences of unwanted pregnancy. Variables
      including use of contraception (OR = 3.3), women's ethnicity (OR = 1.9),
      partner's feelings about pregnancy (OR = 2.0), amount of social support (OR =
      1.2), and mother's instrumental support (OR = 0.85) all affected women's
      perceptions of wanting the pregnancy. These results were used to create a model
      of unwanted pregnancy, beginning before conception and ending with either
      termination of pregnancy or initiation of prenatal care. CONCLUSIONS: The support
      and concern of a partner during pregnancy can have positive consequences for a
      mother's desire to carry out the pregnancy. To increase their commitment to the
      pregnancy and childbirth, partners should be included more in the prenatal care
      process.

PMID- 11251490
TI  - Women's perceptions of outcomes of prenatal case management.
AB  - BACKGROUND: Comprehensive case management is a multidisciplinary, community-based
      service often available to Medicaid-eligible women. The purpose of the study was
      to identify the variety of maternal outcomes, other than birth outcomes,
      attributable to comprehensive prenatal case management. METHOD: This qualitative
      study used a social ecological approach. Twenty-four women were interviewed about
      the outcomes they experienced as a result of comprehensive prenatal case
      management. Ethnographic content analysis was used for data reduction. The
      participants' mean age was 25.4 (SD = 8.4) years, with an average parity of 1.9
      (SD = 1.1). Fifteen participants (68%) had a 12th grade education or less. Ethnic
      minorities were included in the sample. Eleven participants (47%) worked at least
      part-time, although 23 (98%) were receiving Medicaid and 21 (88%) were receiving
      the Women, Infants, and Children's (WIC) supplementary nutrition program.
      RESULTS: The women attributed improvements of various types to the actions of the
      case manager, specifically in the areas of emotional well-being, learning,
      lifestyle behaviors, financial situation, services utilization, and maternal and
      infant physical health. CONCLUSION: Case management appeared to have immediate
      effects on the women, as well as intermediate effects, such as changes in
      lifestyle behaviors and services utilization. The women attributed those changes
      to having a healthy pregnancy.

PMID- 11251491
TI  - Umbilical cord blood collection, banking, and transplantation: current status and
      issues relevant to perinatal caregivers.
AB  - As a result of recent media coverage of cord blood transplantation, expectant
      parents increasingly ask perinatal caregivers about the possibility of collecting
      and saving their newborn child's umbilical cord blood. Umbilical cord blood has
      been used as a source of hematopoeitic stem cells for the treatment of human
      disease since 1988. As a result of these initial successes, cord blood
      collection, banking, and transplantation has become increasingly used worldwide,
      giving rise to several controversies. We have reviewed the current status of the
      indications for cord blood collection, the methods of collection, and safety
      issues related to the cyropreservation of cord blood units. In addition, the
      clinical success of cord blood transplants from related and unrelated donors is
      detailed. We have examined the major issues concerning cord blood transplantation
      as it exists in the year 2000 to provide insight into this exciting area of
      clinical investigation.

PMID- 11251492
TI  - U.S. obstetric procedures, 1998.

PMID- 11251493
TI  - Cesarean section: a worldwide epidemic?

PMID- 11251494
TI  - Looking for an obstetrical caregiver in the United States: one woman's
      experience.

PMID- 11251495
TI  - Confrontation in Kansas City: elective cesareans and maternal choice.

PMID- 11251496
TI  - Does team midwife care increase satisfaction with antenatal, intrapartum, and
      postpartum care? A randomized controlled trial.
AB  - BACKGROUND: Although policymakers have suggested that improving continuity of
      midwifery can increase women's satisfaction with care in childbirth, evidence
      based on randomized controlled trials is lacking. New models of care, such as
      birth centers and team midwife care, try to increase the continuity of care and
      caregiver. The objective of this study was to evaluate the effect of a new team
      midwife care program in the standard clinic and hospital environment on
      satisfaction with antenatal, intrapartum, and postpartum care in low-risk women
      in early pregnancy. METHODS: Women at Royal Women's Hospital in Melbourne,
      Australia, were randomly allocated to team midwife care (n = 495) or standard
      care (n = 505) at booking in early pregnancy. Doctors attended most women in
      standard care, and continuity of the caregiver was lacking. Satisfaction was
      measured by means of a postal questionnaire 2 months after the birth. RESULTS:
      Team midwife care was associated with increased satisfaction, and the differences
      between the groups were most noticeable for antenatal care, less noticeable for
      intrapartum care, and least noticeable for postpartum care. The study found no
      differences between team midwife care and standard care in medical interventions
      or in women's emotional well-being 2 months after the birth. CONCLUSION:
      Conclusions about which components of team midwife care were most important to
      increased satisfaction with antenatal care were difficult to draw, but data
      suggest that satisfaction with intrapartum care was related to continuity of the
      caregiver.

PMID- 11251497
TI  - Team midwifery care in a tertiary level obstetric service: a randomized
      controlled trial.
AB  - BACKGROUND: In 1996 a new model of maternity care characterized by continuity of
      midwifery care from early pregnancy through to the postpartum period was
      implemented for women attending Monash Medical Centre, a tertiary level obstetric
      service, in Melbourne, Australia. The objective of this study was to compare the
      new model of care with standard maternity care. METHODS: In a randomized
      controlled trial, 1000 women who booked at the antenatal clinic and met the
      eligibility criteria were randomly allocated to receive continuity of midwifery
      care (team care) from a group of seven midwives in collaboration with obstetric
      staff, or care from a variety of midwives and obstetric staff (standard care).
      The primary outcome measures were procedures in labor, maternal outcomes,
      neonatal outcomes, and length of hospital stay. RESULTS: Women assigned to the
      team care group experienced less augmentation of labor, less electronic fetal
      monitoring, less use of narcotic and epidural analgesia, and fewer episiotomies
      but more unsutured tears. Team care women stayed in hospital 7 hours less than
      women in standard care. More babies of standard care mothers were admitted to the
      special care nurseries for more than 5 days because of preterm birth, and more
      babies of team care mothers were admitted to the nurseries for more than 5 days
      with intrauterine growth retardation. No differences occurred in perinatal
      mortality between the two groups. CONCLUSIONS: Continuity of midwifery care was
      associated with a reduction in medical procedures in labor and a shorter length
      of stay without compromising maternal and perinatal safety. Continuity of
      midwifery care is realistically achievable in a tertiary obstetric referral
      service.

PMID- 11251498
TI  - Commentary: have we yet learned about the effects of continuity of midwifery
      care?

PMID- 11251499
TI  - Fathers' coping style, antenatal preparation, and experiences of labor and the
      postpartum.
AB  - BACKGROUND: In recent years the trend for fathers in Western postindustrial
      countries to attend childbirth has increased. This study examined the interaction
      between fathers' information-seeking coping predispositions and their level of
      attendance at antenatal classes with respect to their experiences of attending
      childbirth. Associations between fathers' childbirth experiences, their
      relationship with their baby, and level of depressive symptomatology at 6 weeks
      postpartum were also examined. METHODS: A quantitative methodology was employed
      in which 78 fathers completed several questionnaires, some within 6 days of
      childbirth and others at 6 weeks postpartum. RESULTS: Fathers who were
      characterized as high blunters (avoiders) of threat information, from antenatal
      classes reported that experiencing childbirth was less fulfilling than fathers
      with similar coping styles who did not attend classes. Fathers' reports of
      fulfillment and delight while attending childbirth were negatively related to
      their level of depressive symptomatology at 6 weeks postpartum. Levels of
      distress were associated with subsequent depressive symptoms, but their effect
      was removed when preexisting depressive symptoms were partialled out. Fathers
      whose children were born by cesarean delivery used significantly more negative
      adjectives to describe their baby at 6 weeks postpartum compared with those born
      by vaginal delivery. More married fathers attended antenatal classes and reported
      lower levels of depressive symptomatology than unmarried fathers. CONCLUSIONS:
      Although fathers' attendance at antenatal classes may have positive consequences
      for them and their partner, for some fathers, attendance at classes may be
      associated with less positive reports of experiencing childbirth. The way in
      which men experience childbirth may have some influence on their subsequent
      emotional well-being.

PMID- 11251500
TI  - Perinatal outcome in 41 sets of triplets in Jordan.
AB  - BACKGROUND: Triplet births, which have increased greatly throughout the world in
      recent years, have a much greater risk of poor birth outcome than singleton
      births. The purpose of this study was to determine the perinatal outcome
      associated with triplet pregnancies and to compare abdominal delivery with
      vaginal delivery. METHODS: We conducted a retrospective study of 41 sets of
      triplets born between January 1, 1994, and June 30, 1999, at the Princess Badee'a
      Teaching Hospital in Amman, Jordan. The primary outcome measures were perinatal
      mortality and early neonatal complications. RESULTS: Of these sets, 21 triplets
      were delivered vaginally and 20 triplets were delivered by cesarean section. The
      perinatal mortality rate was 260 per 1000 live births in this series, primarily
      due to respiratory distress syndrome. The perinatal deaths occurred to infants
      whose birthweights were primarily 500 to 1500 g (90.6%). Breech presentation was
      associated with a significantly higher perinatal mortality rate than vertex
      presentation (62.5% vs 37.5%). Cesarean delivery was associated with a higher
      perinatal mortality rate than vaginal delivery (30.0% vs 22.2%). CONCLUSIONS:
      These results suggested that cesarean delivery in triplets is not superior to
      vaginal delivery in terms of fetal and early neonatal outcome. The perinatal
      mortality rate was significantly higher than that in other recent series due to
      limited resources in Jordan.

PMID- 11251501
TI  - Commentary: Triplets: a challenge to the obstetric community worldwide.

PMID- 11251502
TI  - Japanese couples' childbirth experiences in Michigan: implications for care.
AB  - BACKGROUND: Subtle cultural differences in the childbirth experience for
      expatriate Japanese couples living in southeast Michigan can sometimes cause
      conflicts between them and American health caregivers. The purpose of this study
      was to examine Japanese couples' perceptions and experiences of prenatal care and
      childbirth in a region of the United States, and to explore the implications for
      providing culturally competent care. METHODS: In this qualitative study, in-depth
      interviews of 11 Japanese couples (n = 22) were conducted at an outpatient
      primary care clinic in southeast Michigan by a team of researchers fluent in the
      Japanese language and knowledgeable about the culture. Participants also
      completed a short questionnaire. RESULTS: The major themes that emerged comprised
      perceptions related to a language barrier, ultrasonography, prenatal vitamin
      supplementation, episiotomy, epidural anesthesia, and practitioner-patient
      relationship. Throughout these six themes it was evident that Japanese health
      care professionals had difficulty accepting health care that was different from
      the care provided in their home country. CONCLUSION: The most striking finding of
      this study was the difficulty for health caregivers to provide culturally
      competent care. Although the program has strongly invested in health
      professionals and support staff who were fluent in Japanese and knowledgeable
      about Japanese culture, conflicts still occurred.

PMID- 11251503
TI  - The dilemma of postnatal mother-to-child transmission of HIV: to breastfeed or
      not?
AB  - The promotion of nearly universal breastfeeding has played an important role in
      improving child health by providing optimum nutrition and protection against
      common childhood infections, and by promoting child spacing. Unfortunately, it
      has become clear that breastfeeding is responsible also for much of the
      increasing burden of worldwide pediatric human immunodeficiency virus (HIV)
      infection, especially in the developing nations (12-14% additional risk of HIV
      infection transmitted by breastfeeding; 35% total proportion of all HIV-infected
      children in an area infected through breastfeeding). Several factors influence
      the transmission of HIV by breastfeeding, including whether a woman acquires her
      infection during breastfeeding (29% risk of transmission) or before pregnancy (7
      10% risk of breastfeeding transmission),the degree of maternal plasma and
      breastmilk viral load, and the presence of mastitis. In areas of the world where
      adequate sanitary replacement feeding is not available, the decision to withhold
      breastfeeding so as to decrease HIV transmission may lead to increased rates of
      child morbidity and mortality from diarrheal and respiratory diseases, and
      malnutrition. This review summarizes current data on the pathophysiology of
      breastfeeding transmission of HIV infection, the risk factors for and incidence
      rates of transmission, and the feasibility of possible alternatives to exclusive
      breastfeeding in the setting of maternal HIV infection. Clearly, women must be
      fully informed about the risks of breastfeeding transmission of HIV, the risks of
      morbidity and mortality among nonbreastfed infants, and the expense and
      availability of procuring adequate replacement formula. If an uninterrupted
      access to a nutritionally adequate breastmilk substitute that can be safely
      prepared is ensured (as is possible in industrialized countries), HIV-infected
      women should be counseled not to breastfeed their infants.

PMID- 11251504
TI  - Epidural analgesia, intrapartum fever, and neonatal outcomes.

PMID- 11251505
TI  - Childbirth advice literature as it relates to two childbearing ideologies.

PMID- 11251506
TI  - Sheila Kitzinger's letter from Europe: the waterbirth debate up-to-date.

PMID- 11251507
TI  - 432 Somali women's birth experiences in Canada after earlier female genital
      mutilation.
AB  - BACKGROUND: Women with previous female genital mutilation (sometimes referred to
      as circumcision) are migrating, with increasing frequency, to countries where
      this practice is uncommon. Many health care professionals in these countries lack
      experience in assisting women with female genital mutilation during pregnancy and
      birth, and they are usually untrained in this aspect of care. Somali women who
      customarily practice the most extensive form of female mutilation, who were
      resident in Ontario and had recently given birth to a baby in Canada, were
      surveyed to explore their perceptions of perinatal care and their earlier genital
      mutilation experiences. METHOD: Interviews of 432 Somali women with previous
      female genital mutilation, who had given birth to a baby in Canada in the past
      five years, were conducted at their homes by a Somali woman interviewer. RESULTS:
      Findings suggested that women's needs are not always adequately met during their
      pregnancy and birth care. Women reported unhappiness with both clinical practice
      and quality of care. CONCLUSIONS: Changes in clinical obstetric practice are
      necessary to incorporate women's perceptions and needs, to use fewer
      interventions, and to demonstrate greater sensitivity for cross-cultural
      practices and more respectful treatment than is currently available in the
      present system of care.

PMID- 11251508
TI  - Single room maternity care and client satisfaction.
AB  - BACKGROUND: Single room maternity care is the provision of intrapartum and
      postpartum care in a single room. It promotes a philosophy of family centered
      care in which one nurse cares for the family consistently throughout the
      intrapartum and postpartum periods. At B.C. Women's Hospital, a tertiary level
      obstetric teaching hospital in Vancouver, British Columbia, a seven-bed, single
      room maternity care unit was developed and opened as a demonstration project. As
      part of the evaluation of this unit, client satisfaction was compared between
      women enrolled in single room maternity care and those in a traditional setting.
      METHOD: The study group included 205 women who were admitted to the single room
      maternity care unit after meeting the low-risk criteria. Their responses on a
      satisfaction survey were compared with those of a historical comparison group of
      221 women meeting the same eligibility criteria who were identified through chart
      audits 3 months before the single room maternity care unit was opened. A second,
      concurrent comparison group comprised 104 women who also met eligibility
      criteria. RESULTS: Study group women were more satisfied than comparison groups
      in all areas evaluated, including provision of information and support, physical
      environment, nursing care, patient education, assistance with infant feeding,
      respect for privacy, and preparation for discharge. CONCLUSIONS: Single room
      maternity care was associated with a significant improvement in client
      satisfaction because of many factors, including the physical setting itself,
      avoidance of transfers, and improved continuity of nursing care.

PMID- 11251509
TI  - Memory for labor pain: a review of the literature.
AB  - BACKGROUND: Women's ability and accuracy in recalling labor pain are widely
      debated, even though clinicians commonly use such retrospective information in
      their practice. The objectives of this paper are to review the literature to
      establish if labor pain is forgotten, if recall is accurate, factors that affect
      the accuracy of recall, and consequences of recall. METHODS: An electronic search
      of Medscape, Psychlit, Bath Information and Data Services, and CINAHL between
      1990 and 1999 was undertaken using the key words "labor" and "labour," "pain,"
      and "memory." Each key word produced thousands of hits, but the combination of
      all three was surprisingly unsuccessful. This review, therefore, used a manual
      and print search and a detailed knowledge of work in this and related fields.
      RESULTS: The literature was relatively limited, and many studies demonstrated
      methodological problems. Inductive and deductive analysis suggested that women do
      not completely forget labor pain, and recall is often vivid but not always
      entirely accurate. CONCLUSIONS: Memories of labor pain can evoke intense negative
      reactions in a few women, but are more likely to give rise to positive
      consequences related to coping, self-efficacy, and self-esteem.

PMID- 11251510
TI  - The meaning of labor pain.

PMID- 11251511
TI  - Women's request for a cesarean section: a critique of the literature.
AB  - BACKGROUND: The consistently high cesarean section rate in most developed Western
      countries has been attributed in part to maternal request. This controversial
      view demands critical analysis. This paper provides a critique of published
      research relating to women's request for cesarean delivery. METHOD: A search of
      the major databases was undertaken using the search term "cesarean section" with
      "maternal request," "decision-making," "patient-participation," "decision-making
      patient," "patient-satisfaction," "patient-preference," and "maternal-choice."
      Ten research articles examining women's preferred mode of birth were retrieved,
      nine of which focused on women's preference for cesarean delivery. RESULTS: The
      methodology of some studies may result in overreporting women's request for a
      cesarean delivery. The role of the woman's caregiver in the generation,
      collection, and entry of data, and the occurrence of post hoc rationalization,
      recall bias, and women's tendency to be less critical of their care immediately
      after birth are possible areas of concern. Due consideration is rarely given to
      the influence of obstetric risk for women who may be requesting a cesarean
      section or to the information women used in making their decision. Women's
      perceptions of their involvement in decision-making regarding cesarean section
      are used to draw conclusions regarding women's request. CONCLUSIONS: Few women
      request a cesarean section in the absence of current or previous obstetric
      complications. The focus on women's request for cesarean section may divert
      attention away from physician-led influences on the continuing high cesarean
      section rates.

PMID- 11251512
TI  - A blatant misuse of power?

PMID- 11251513
TI  - Pregnant and imprisoned in the United States.
AB  - This article is excerpted from a report by Amnesty International, entitled "Not
      Part of My Sentence": Violations of the Human Rights of Women in Custody, March
      1999. The article describes violations of the human rights of pregnant women and
      mothers who are incarcerated in prisons and jails in the United States. Many of
      the practices employed are not in compliance with international standards and are
      also prohibited by federal and state laws in the United States. In 1997-1998,
      more than 2200 pregnant women were imprisoned and more than 1300 babies were born
      in prisons. In at least 40 states, babies are taken from their imprisoned mothers
      almost immediately after birth or at discharge from the hospital. International
      standards restrict the use of restraints to limited situations. Restraints are
      used as a matter of course in the United States, including on women in labor or
      immediately after birth, who may be taken to a hospital in handcuffs and chained
      by a leg to the bed. Amnesty International calls for governments and authorities
      to take urgent action that will ensure that the laws, regulations, policies, and
      practices for which they are responsible rigorously conform to international
      standards and respect the human rights of women deprived of their liberty.

PMID- 11251514
TI  - Using music during childbirth.
AB  - BACKGROUND: The application of music in pain management has become popular in the
      past two decades. This article describes the responses of primiparas to the use
      of music therapy during the births of their children. METHOD: Eleven women who
      attended childbirth education classes in Brantford, Ontario, Canada, volunteered
      to participate in a music therapy exercise. During pregnancy each participant
      selected preferred music, listened to it daily, and received instruction about
      focused listening. Within 72 hours after birth they were interviewed about their
      use of music as a coping strategy during labor. RESULTS: Women selected the
      combination of music and labor support as a helpful coping strategy during labor.
      All women used the music during labor to help distract them from the pain or
      their current situation. CONCLUSION: The planned use of music by mothers and
      caregivers can be an aid to prenatal preparation and an important adjunct in pain
      and stress management during labor and birth.

PMID- 11251515
TI  - Less than meets the eye: the consumer product safety commission's campaign
      against bed-sharing with babies.

PMID- 11251516
TI  - Challenges for birth-related research.

PMID- 11251517
TI  - The long-term results of Anderson-Hynes pyeloplasty.
AB  - OBJECTIVES: To examine the durability of open pyeloplasty for pelvi-ureteric
      junction obstruction. PATIENTS AND METHODS: The records of 56 Anderson-Hynes
      pyeloplasties undertaken by two surgeons between 1981 and 1994 were examined.
      Attempts were made to trace all patients and for them to undergo diuretic
      renography to examine the current status of the operated renal unit. RESULTS: In
      all, 41 evaluable patients were identified; 24 agreed to return for reassessment.
      The mean (range) time from surgery was 10.6 (6-19) years. The results showed an
      improvement over the preoperative split renal function in 19 patients (79%) and
      an improvement in drainage in 23 (96%). CONCLUSIONS: The Anderson-Hynes
      pyeloplasty is an excellent procedure for treating pelvi-ureteric junction
      obstruction, and produces a lasting improvement in function and drainage in most
      patients. It is the 'gold standard' against which newer techniques should be
      compared.

PMID- 11251518
TI  - A conservative approach to major blunt renal lacerations with urinary
      extravasation and devitalized renal segments.
AB  - OBJECTIVES: To determine the feasibility of a conservative (expectant) approach
      to major blunt renal laceration with urinary extravasation and devitalized renal
      segments. PATIENTS AND METHODS: All patients treated conservatively who presented
      between 1990 and 1999 with major renal laceration (grade 4 and 5) were
      retrospectively reviewed to determine whether urinary extravasation and
      devitalized segments adversely affected the outcome. For each patient the data
      collected included the initial emergency department evaluation, findings on
      computed tomography, associated injuries, duration of hospital stay, transfusion
      requirements, complications and follow-up imaging. RESULTS: Of 20 patients who
      sustained blunt trauma resulting in a major renal laceration (five grade 5 and 15
      grade 4) with urinary extravasation, 11 had coexisting devitalized segments.
      There was a statistically significant difference in the length of hospital stay
      (16.3 vs 7.3 days), blood transfusions (six vs two patients, P < 0.08) and the
      need for delayed surgical intervention (nine vs two, P < 0.01) between patients
      with and with no devitalized segments, respectively. Urinary extravasation
      spontaneously resolved in two of 11 patients with and in seven of nine with no
      devitalized segment, respectively (P < 0.05) CONCLUSIONS: Urinary extravasation
      will resolve spontaneously in most patients with blunt renal trauma, and
      expectant treatment does not adversely affect the outcome or prolong
      hospitalization. In patients who present with a major renal laceration associated
      with devascularized segments, conservative management is feasible in those who
      are clinically stable with blunt trauma. However, the physician must be
      especially aware of the probable complications within this subset of patients.

PMID- 11251519
TI  - Urological complications after living-donor renal transplantation.
AB  - OBJECTIVE: To determine the incidence and management of urological complications
      after 1200 consecutive live-donor renal transplantations, all of which were
      carried out in one centre; the possible risk factors and the effect on patient
      and graft survival were also assessed. PATIENTS AND METHODS: Data were retrieved
      from an electronic database; the incidence of urological complications was
      determined, and correlated with relevant risk factors by univariate and
      multivariate analysis. The effect on patient and graft survival was assessed
      using Kaplan-Meier statistics. RESULTS: There were 100 complications in 96
      patients (8%); urinary leaks occurred in 37, ureteric strictures in 23 and
      lymphoceles causing ureteric obstruction in 17. Percutaneous needle biopsy was
      complicated by haematuria and clot anuria in six patients. Late complications
      included 11 cases of stones, four of bladder malignancy and two of haemorrhagic
      cystitis. There was evidence that the age of the recipients (< 10 years), method
      of establishing urinary continuity (uretero-ureteric anastomosis) and a high dose
      of steroids had an independent positive effect on the incidence of urological
      complications. However, their development did not influence graft or patient
      survival. CONCLUSION: When there is meticulous attention to the technical
      details, renal transplantation should incur few urological complications. Early
      intervention with percutaneous drainage reduces morbidity and the likelihood loss
      of graft function. Proper and prompt management should not affect the graft
      and/or the patient's survival.

PMID- 11251520
TI  - The influence of a high-oxalate/low-calcium diet on calcium oxalate renal stone
      risk factors in non-stone-forming black and white South African subjects.
AB  - OBJECTIVE: To evaluate the influence of a high-oxalate/low-calcium diet on
      calcium oxalate stone risk factors in both black South Africans (who are largely
      immune to kidney stones) and white South Africans (in whom stones are more
      common). SUBJECTS AND METHODS: Urinary and dietary variables were examined in 11
      black and 11 white South African men. None of the subjects had had a kidney stone
      or any metabolic illness. Their normal domestic food intake was assessed using a
      semiquantitative food frequency questionnaire. Subjects were given a standardized
      high-oxalate/low-calcium diet for 3 days; 24-h urine samples were collected
      before the protocol and during the final day. The samples were analysed using
      routine modern laboratory techniques. The urine analysis data were used to
      calculate the Tiselius risk index and the relative urinary supersaturations of
      calcium oxalate, uric acid and calcium phosphate. RESULTS: Urine analysis showed
      an intriguing anomaly; black subjects had significantly higher urinary pH and
      oxalate values than whites (6.50 vs 6.21 and 0.23 vs 0.14 mmol/24 h,
      respectively), while their urinary citrate was lower (1.47 vs 3.69 mmol/24 h). In
      addition, the Tiselius risk index and relative supersaturation of calcium oxalate
      were higher in black subjects. These results are contrary to those which might
      have been reasonably expected when comparing stone-free and stone-prone groups.
      After the dietary protocol, the only urinary variable which changed significantly
      was urinary oxalate, which increased by 57% in whites. CONCLUSION: Factors which
      are conventionally used to assess stone risk (pH, oxaluria, citraturia, relative
      supersaturation) are not helpful in identifying why South African blacks are
      relatively immune to stones. We suggest that relatively lower oxalate absorption
      rates may be a physiological feature of this racial group.

PMID- 11251521
TI  - Prognostic evaluation of transcatheter arterial embolization for unresectable
      renal cell carcinoma with distant metastasis.
AB  - OBJECTIVE: To evaluate the efficacy of transcatheter arterial embolization (TAE)
      in patients with unresectable renal cell carcinoma (RCC) and distant metastasis
      at the time of diagnosis. PATIENTS AND METHODS: The study included 54 patients
      with histologically defined RCC (by biopsy in 28 and autopsy in 26) who were
      unable to undergo nephrectomy mainly because their performance status was poor
      (score > or = 2). The patients were classified into two groups; 24 patients who
      underwent TAE with ethanol and 30 patients who did not. The two groups were
      compared for several clinical factors, mainly focusing on the prognosis. RESULTS:
      There were no significant differences in the clinical factors, including
      performance status, tumour diameter, vascular invasion, lymph node involvement,
      adjuvant therapy, metastatic organs or the number of metastases between the
      groups. However, the proportion of patients with para-neoplastic signs in those
      undergoing TAE was greater than that in those not, and the difference was
      significant (chi squared 0.35, P < 0.05). The median survival of the two groups
      was 229 days (TAE) and 116 days (no TAE). The 1-, 2- and 3-year survival rates in
      the TAE group were 29%, 15% and 10%, respectively, and in those not undergoing
      TAE were 13%, 7% and 3%, respectively. Those undergoing TAE had a significantly
      better prognosis than those who did not (P = 0.019). The adverse effects in
      patients undergoing TAE with ethanol included fever, back pain on the affected
      side, nausea and vomiting, but all the patients recovered from these adverse
      effects. CONCLUSION: TAE with ethanol is a safe and effective treatment for
      patients with unresectable disseminated RCC and a poor performance status; TAE
      with ethanol not only induces ablation of the primary tumour, but also prolongs
      survival.

PMID- 11251522
TI  - Piezoelectric extracorporeal shockwave lithotripsy of distal ureteric calculi:
      assessment of shockwave focusing with unenhanced spiral computed tomography.
AB  - OBJECTIVE: To assess the effects of the interposition of pelvic bones and
      abdominal gas in the shockwave pathway during piezoelectric extracorporeal shock
      wave lithotripsy (ESWL) of distal ureteric stones. PATIENTS AND METHODS: The
      study included 35 patients who were evaluated with unenhanced spiral computed
      tomography (CT), used according to their positioning during ESWL. The shockwave
      pathway was simulated on the sagittal and coronal views crossing the ureteric
      calculi, allowing a theoretical evaluation of the effective shockwave focusing
      (with no bone or gas interference). Vertical and oblique approaches were
      statistically compared for bone and gas interposition. RESULTS: Overall, the
      effective shockwave focusing during in situ piezoelectric ESWL of distal ureteric
      stones was 71% of the theoretical area. The interposition of bone and gas was
      significantly lower for an oblique access than for a vertical approach in the
      sagittal plane (P < 0.001 and 0.03 on the sagittal and coronal views,
      respectively). Using stepwise logistic regression, the difference between
      vertical and oblique accesses in the sagittal plane was mainly affected by the
      bladder volume (P < 0.001). On the coronal views, the interposition of bone and
      gas affected 31 patients (89%). Such interference was eliminated in 73% of the
      patients with a contralateral inclination of the shockwave axis in the coronal
      plane. CONCLUSION: The interposition of pelvic bones and abdominal gas in the
      shockwave pathway can affect the performance of piezoelectric ESWL of distal
      ureteric stones. While awaiting clinical confirmation of these theoretical data,
      we recommend that patients are treated with the bladder full and that the
      shockwave generator is inclined in both the coronal and sagittal planes.

PMID- 11251523
TI  - An assessment of the clinical efficacy of intranasal desmopressin spray in the
      treatment of renal colic.
AB  - OBJECTIVES: To assess the efficacy of desmopressin nasal spray compared with
      diclofenac given intramuscularly in patients with acute renal colic caused by
      urolithiasis. PATIENTS AND METHODS: The study included 61 patients randomized
      into three different groups; group A received desmopressin (40 microg, nasal
      spray), group B diclofenac (75 mg) intramuscularly and group C, both desmopressin
      and diclofenac. Pain was assessed using a visual analogue scale (a 10-cm
      horizontal scale ranging from 'no pain' to 'unbearable pain') at baseline, 10, 20
      and 30 min after administering the treatments. RESULTS: On admission, the pain
      level was the same in all three groups. At 10 min the pain decreased in all
      groups to a level that was not significantly different. At 20 min groups B and C
      had similar mean pain levels (3.7), whereas in group A it was 5.0. At 30 min,
      groups B and C scored 2-3, and group A 5.6. All three treatments were equally
      effective at 10 and 20 min but at 30 min there was a stabilization/slight
      increase in pain level in group A. CONCLUSIONS: Desmopressin has several
      advantages, e.g. ease of administration, simplicity of delivery and apparent lack
      of side-effects, which makes it suitable for ambulatory use. Desmopressin acts
      rapidly and seems to be effective in both single and combined therapy with
      diclofenac; it decreases the need for a second treatment and increases the
      analgesic effect of diclofenac. Some patients responded well to desmopressin,
      with rapid and complete pain relief. These results indicate that desmopressin may
      be used to treat renal colic either alone or combined, increasing the analgesic
      effect of other drugs. More studies are needed to validate and confirm the
      results; it would also be useful to determine factors that may identify the
      subgroup of patients who respond quickly and with almost complete pain relief.

PMID- 11251524
TI  - Haematuria in Africa: is the pattern changing?
AB  - OBJECTIVE: To study the aetiological factors and clinical presentation of
      haematuria as seen in a tertiary healthcare centre in a developing country in
      Africa. PATIENTS AND METHODS: The study comprised a retrospective review of the
      diagnostic indices and notes of patients with macroscopic haematuria presenting
      at the Ahmadu Bello University Teaching Hospital, Zaria, Nigeria, over a 7-year
      period from 1985 to 1991. RESULTS: Of a total of 2726 urology patients and 11 232
      surgical patients, 482 had haematuria (17.7% and 4.3%, respectively, 387 males
      and 95 females, ratio 4.1 : 1, mean age 44.8 years, range 6-80). Many presented
      late with advanced malignant disease (T3, T4). Investigations useful in the
      diagnosis were urinary cytology, intravenous urography and cysto-urethroscopy.
      Common causes of haematuria were bladder carcinoma in 142 (31%), benign prostatic
      hypertrophy in 64 (14%) and urinary stones in 54 (12%). CONCLUSION: Recurrent
      haematuria in patients over 30 years of age in this environment should be
      considered or deemed to be caused by malignancy until confirmed otherwise. An
      educational programme is required to alert the population to the significance of
      haematuria as a symptom demanding a thorough investigation before treatment. This
      would need support by a haematuria service for accelerated diagnosis and
      treatment.

PMID- 11251525
TI  - Couch or crouch? Examining the prostate: a randomized study comparing the knee
      elbow and the left-lateral position.
AB  - OBJECTIVE: To compare two methods of examining the prostate, the knee-elbow (KE)
      and left-lateral (LL) positions, to establish which allows a more complete
      examination, and to determine if there is any difference in patients' perception
      of pain or embarrassment for either method. PATIENTS AND METHODS: All men
      attending two urology clinics who required a prostate examination were eligible
      for the study. Both the KE and LL methods were used for each participant, by the
      same clinician. The order in which the examinations were conducted was randomized
      using the last digit of the patient's hospital number. RESULTS: Five clinicians
      examined 117 men; three patients refused to participate and the examination data
      were incomplete for two. Irrespective of the order in which the examinations were
      conducted (P = 0.6), the KE position permitted a greater proportion of the
      prostate to be palpated (Wilcoxon signed-ranks test, z = -4.7, P < 0.001) in 35%
      of patients, but there was no difference in 60%. Most patients found the
      examinations equally painful and embarrassing. However, for those who expressed a
      difference, the KE was 1.9 times more comfortable than the LL position and twice
      as embarrassing. CONCLUSION: The two methods of prostate examination were equal
      for completeness of examination, pain and embarrassment in most patients.
      However, the KE offers an alternative to the LL position for those patients in
      whom the prostate is difficult to palpate or who find the examination painful.

PMID- 11251526
TI  - Low frequency of microsatellite instability in hereditary prostate cancer.
AB  - OBJECTIVE: To investigate whether there is widespread microsatellite instability
      (MSI) in families with hereditary prostate cancer (HPC). PATIENTS AND METHODS:
      Eighty-four prostate tumours from 80 Swedish men in 35 families with HPC were
      screened for genetic instability at microsatellite marker loci BAT-25, BAT-26,
      BAT-34C4, D2S123 and D17S250. RESULTS: MSI was detected in only five individuals
      from different families. Three tumours (4%) were unstable at more than two MSI
      loci and hence classified as high-frequency MSI (MSI-H) according to a previous
      definition. Interestingly, two of the MSI-H tumours were from patients in
      families with both HPC and familial colon cancer. CONCLUSIONS: Widespread MSI is
      a rare event in hereditary prostate cancer, indicating that defective DNA
      mismatch repair is not an important element in the genesis of HPC.

PMID- 11251527
TI  - Patterns of referral, management and survival of patients diagnosed with prostate
      cancer in Scotland during 1988 and 1993: results of a national, retrospective
      population-based audit.
AB  - OBJECTIVES: To examine patterns of referral, management and survival of men with
      prostate cancer, and to document changes over time. PATIENTS AND METHODS: All men
      registered with prostate cancer in 1988 and 1993 were identified from the
      Scottish Cancer Registry. Data were abstracted according to standard definitions
      from the available medical records of 930 men in 1988 and 1355 in 1993. RESULTS:
      There was limited evidence of multidisciplinary care, with only 8% of patients in
      1988 being managed by both a urologist and a clinical oncologist within a year of
      diagnosis, increasing to 13% in 1993. Only a small proportion of patients were
      managed by clinical oncologists during the first year of care (14% in 1988 and
      20% in 1993). Documentation of thorough staging information was poor, with a T
      stage being recorded in <30% of cases in both years. Documentation of metastatic
      status increased from 53% to 63% between 1988 and 1993, paralleling an increase
      in the use of bone scans. The proportion of cases with pathological grading
      obtained at diagnosis increased from 63% in 1988 to 68% by 1993. The use of PSA
      testing and core biopsies increased between the years while the use of
      transurethral prostatectomy decreased. More patients received radical
      radiotherapy within a year of diagnosis in 1993 than 1988, increasing from 6% to
      9%, and more radical prostatectomies were also undertaken (0.2% to 2.3%).
      Nonetheless, most patients (81% in 1993) with no documented evidence of
      metastases received no active intervention (radical radiotherapy, radical
      prostatectomy, or 'watchful waiting'). The survival at 5 years increased
      nonsignificantly from 34% for the 1988 cohort to 38% for the 1993 cohort.
      CONCLUSION: This audit reveals considerable inconsistency in the management of
      men with prostate cancer in Scotland. Against a background of controversy about
      numerous aspects of the management of this disease, the need for a
      multidisciplinary approach, comprehensive staging and appropriate documentation
      is highlighted.

PMID- 11251528
TI  - The serum level of the amino-terminal propeptide of type I procollagen is a
      sensitive marker for prostate cancer metastasis to bone.
AB  - OBJECTIVE: To assess the level of a bone-formation marker, the amino-terminal
      propeptide of type I procollagen (PINP), for its utility in indicating bone
      metastasis in patients with prostate cancer. PATIENTS AND METHODS: Several bone
      formation markers, i.e. PINP, the carboxy-terminal propeptide of type I
      procollagen (PICP), bone-specific alkaline phosphatase (BALP), and bone Gla
      protein (BGP), a bone resorption marker (pyridinoline cross-linked carboxy
      terminal telopeptide, ICTP), and prostate specific antigen (PSA) were measured in
      40 patients without and 25 patients with bone metastasis. No patient had
      undergone previous treatment, except for six who developed bone metastasis while
      undergoing hormone therapy. RESULTS: All markers except BGP were significantly
      higher in patients with bone metastasis than in those without. The levels of PINP
      correlated best with the extent of disease, although the levels of PSA, BALP and
      ICTP also correlated well. While PINP had the largest area under the receiver
      operator characteristic curve, PSA, BALP and ICTP also produced useful curves.
      CONCLUSION: The bone formation marker PINP seems to be useful for discriminating
      patients with and without bone metastasis. PINP may help in the early and
      accurate diagnosis of bone metastasis in such patients.

PMID- 11251529
TI  - Corporal plication for penile curvature caused by Peyronie's disease: the
      patients' perspective.
AB  - OBJECTIVE: To determine the acceptability by patients of corporal plication for
      Peyronie's disease. PATIENTS AND METHODS: A postal questionnaire was sent to 69
      patients who had undergone corporal plication for Peyronie's disease between 1992
      and 1999, to ascertain the subjective outcome and acceptance by the patients and
      their sexual partners of the results of the procedure. Of the 65 patients who
      were still alive, 44 (68%) returned the questionnaire. RESULTS: The mean (range)
      follow-up was 4.1 (0.5-7.25) years and the mean age of the patients 54.6 (32-80)
      years. Of the 44 patients responding, 24 (55%) were sexually active; after
      surgery, 16 (36%) had significant impairment of erections, seven (16%) continued
      to have significant penile discomfort and 15 (34%) could feel nodules at the
      suture site. Twenty-five (57%) patients reported a mild and six (14%) a severe
      persistent penile deformity; 40 (90%) reported having a shorter penis, of whom 22
      (55%) thought it significant. Overall, 14 (32%) reported 'numbness' of the glans
      penis. Only 23 (52%) of the patients would recommend the surgery, with 25 (57%)
      reporting a deterioration in their overall quality of life. Of the partners of
      the evaluable patients, 38 (86%) responded, and a significant deterioration in
      sexual performance was reported by 19 (35%). CONCLUSIONS: Overall, the long-term
      results of corporal plication appear to be disappointing. These poor results
      could be related to a current lack of understanding of the natural history and
      progression of the disease, to case selection, or to the surgery. We intend to
      use these results to counsel our patients before such surgery and inform them of
      the possible outcome in the long term.

PMID- 11251530
TI  - Effective daily treatment with clomipramine in men with premature ejaculation
      when 25 mg (as required) is ineffective.
AB  - OBJECTIVE: To determine whether men with premature ejaculation who fail to
      respond to 25 mg clomipramine as needed improve when taking 10-30 mg clomipramine
      daily. SUBJECTS AND METHODS: Four men with premature ejaculation whose
      ejaculation latencies increased minimally or not at all when taking 25 mg
      clomipramine as needed participated in a prospective 12-week study consisting of
      four treatment phases, beginning with baseline (0 mg) and progressing through
      increasing daily doses of 10, 20, and 30 mg clomipramine. The subjects maintained
      daily logs of their sexual activities and estimated their ejaculatory response,
      sexual arousal and penile rigidity during intercourse. The subjects were
      contacted 8-15 weeks after the experiment to assess their satisfaction with and
      continued use of clomipramine. RESULTS: There was a dose-response effect on
      ejaculatory latency with increasing levels of clomipramine; 30 mg increased the
      latency from 25 s to 220 s, a clinically significant increase. In addition, 30 mg
      taken daily was significantly more effective than 25 mg as required. Other
      variables of sexual response (sexual interest, arousal and penile rigidity) were
      unaffected. At follow-up all four subjects expressed satisfaction and three
      continued the dose. CONCLUSION: Men with premature ejaculation who do not respond
      to clomipramine 'as required' are probably not insensitive to pharmacological
      treatment, but may simply require higher doses or a different regimen. All four
      subjects improved when taking daily clomipramine at varying doses. These results
      suggest that if initial treatment is unsuccessful, 20-30 mg daily clomipramine
      should be considered.

PMID- 11251531
TI  - Trends in testicular carcinoma in England and Wales, 1971-99.
AB  - OBJECTIVES: To examine incidence, mortality and survival trends in England and
      Wales for testicular cancer, using the recently developed national cancer and
      national mortality databases. METHODS: The directly age-standardized incidence
      rates for testicular cancer in England and Wales were calculated for the period
      1971-97 and age-standardized mortality for years 1971-99. Trends in the data were
      then assessed, including the influence of social deprivation on testicular cancer
      incidence and survival. RESULTS: The number of newly diagnosed cases of
      testicular carcinoma in 1971-97 in England and Wales increased from almost 650 to
      1400. The age-standardized rates were 2.9 per 100000 cases in 1971 and 5.4 per
      100000 in 1997, an increase of 88% over 26 years. There was a large decrease in
      mortality since the mid-1970s, with an age-standardized mortality of < 0.5 per
      100000 since 1985. For men with testicular carcinoma diagnosed in 1991-93, the 1
      year relative survival was almost 98% and 5-year relative survival almost 95%,
      compared with 82% and 69%, respectively, for men diagnosed during 1971-75. There
      is a 'deprivation gap' for the 5-year survival of > 6% in favour of the most
      affluent socio-economic group, with no significant change over recent years.
      CONCLUSIONS: The incidence of testicular cancer is increasing in England and
      Wales, consistent with the trend documented in other developed countries. The
      reduction in mortality has been marked since the mid-1970s, reflecting improved
      cancer management, in particular the introduction of platinum-based chemotherapy
      regimens for advanced disease. Survival rates in England and Wales are as good as
      in other European countries. Further developments in chemotherapy are unlikely to
      produce such a marked improvement in survival rates again, and minimizing the
      effect of social status on survival rates should be an important target of future
      care.

PMID- 11251532
TI  - Anogenital electrical stimulation as treatment of urge incontinence in children.
AB  - OBJECTIVES: To evaluate retrospectively the result of anogenital afferent
      stimulation (AGAS) in neurological healthy children with therapy-resistant urge
      incontinence. PATIENTS AND METHODS: The study included 48 children (24 girls and
      24 boys, 5-14 years old) with a diagnosis of bladder instability verified by
      cystometry in all. Anogenital afferent stimulations were applied using a battery
      powered dual constant-current stimulator. The children were stimulated
      continuously at 10 Hz for 20 min once or twice daily and if required the children
      and/or the parents continued to apply the treatment at home. For home stimulation
      a single (anal) channel stimulator was used. The patients were instructed to
      stimulate for 20 min at maximum intensity two to three times a week until the
      effects were optimal. The outcome was evaluated retrospectively by comparing
      voiding/incontinence diaries obtained before and at the follow-up 6-12 months
      after the end of treatment. RESULTS: AGAS was applied at the clinic for a median
      (range) of 9 (4-20) times. Thirty-one children continued with home stimulation
      for another 25 (5-96) sessions. At the follow-up, 18 children were cured and
      another seven improved, with a leakage score of less than half that before
      treatment. The treatment was well tolerated by most children. CONCLUSIONS:
      Anogenital afferent stimulation is an effective, potentially curative treatment
      in children with severe urge incontinence. Home stimulation is a well accepted
      adjuvant to treatment at the clinic and improves the outcome.

PMID- 11251533
TI  - Excessive sac pressures: the pathogenesis and innocence of hydroceles in
      children.
AB  - OBJECTIVE: To determine whether paediatric hydroceles result entirely from a
      small-calibre patent processus vaginalis, allowing free communication between the
      abdominal cavity and hydrocele sac, or whether there are other mechanisms.
      PATIENTS AND METHODS: Twenty-five hydroceles were studied prospectively in 24
      boys (aged 18-132 months). Consent for the intraoperative measurements was
      obtained before surgery. The hydrocele was repaired under general anaesthesia
      with endotracheal intubation, using a standard approach, taking care not to open
      the sac during mobilization. Intra-abdominal pressures during surgery were
      measured indirectly via a nasogastric tube after gastric decompression. The
      pressure in the sac was measured via a 20 G intravenous cannula inserted via a
      purse-string suture. The relative pressure was then calculated by subtracting the
      intra-abdominal from the sac pressure. The effects of age and laterality were
      evaluated. RESULTS: The median (range) intra-abdominal, sac and relative
      pressures were 8 (2-18), 11 (3-30) and 4 (3-30) cmH2O, respectively. The sac
      pressure in the sac was greater than the intra-abdominal pressure in 17 of 25
      (68%; P = 0.004) patients. Age or laterality had no significant influence on any
      of the pressures. CONCLUSIONS: These results suggest that in a significant
      proportion of hydroceles in children the pressures are higher than the intra
      abdominal pressure. Therefore, they cannot be explained simply as a freely
      communicating, narrow-calibre processus. In addition, the pressures may reach
      levels which are potentially damaging to the testis.

PMID- 11251534
TI  - Antenatal renal pelvic measurements: what do they mean?
AB  - OBJECTIVE: To analyse data on cases with urological abnormalities recorded over a
      15-year period (1984-98) by the Northern Region Congenital Abnormality Survey
      (NorCAS), with special reference to fetal renal pelvic measurements. MATERIALS
      AND METHODS: Data on all urological cases recorded in the NorCAS database and in
      notification documents forwarded from hospitals in the Northern Region were
      extracted and incorporated in a separate unattributable database for analysis.
      Specific fields for filing recorded fetal renal pelvic measurements with their
      corresponding gestational ages were inserted; it was ensured as far as possible
      that these measurements were made in the anteroposterior plane. RESULTS: The
      total number of cases analysed was 2737; a measurement of the fetal renal pelvis
      was recorded in 813, and more than once in 468, giving 1301 measurement episodes
      with the corresponding gestational ages, pregnancy and postnatal outcome. The
      male/female (M/F) ratio was significantly higher in those cases which had a fetal
      renal pelvic measurement recorded than in those which had not. This was because
      there was a 12/1 M/F ratio in measured cases of vesico-ureteric reflux (VUR). Few
      cases of VUR had a fetal renal pelvic measurement recorded. The difference in the
      fetal renal pelvic measurements between those cases which were normal postnatally
      and those which had a structural abnormality, an obstructive lesion or VUR became
      significant at 7 mm and at 18 weeks of gestational age. Over the whole period the
      proportion of cases in which micturating cysto-urethrography was technically
      possible and might have contributed to the diagnosis was 28.5%; the highest was
      44.1% in 1998. CONCLUSIONS: Antenatal renal dilatation occurs infrequently in the
      presence of VUR and when it does, the fetus will probably be male. Antenatal
      ultrasonography is unlikely to contribute to detecting VUR in females, the gender
      in whom early diagnosis is particularly desirable. Other means of suspecting VUR
      antenatally, e.g. the family history or genetic coding, may be more valuable. A
      measurement of the fetal renal pelvis of > or = 7 mm at a gestational age of 18
      weeks should prompt subsequent careful ultrasonography during the pregnancy and
      early postnatal investigation of the urinary tract. The diagnosis of VUR should
      not be excluded because the fetal renal pelvis is only minimally dilated if the
      fetus is female.

PMID- 11251535
TI  - Tumour angiogenesis and Ki-67 expression in phaeochromocytoma.
AB  - OBJECTIVE: To determine the expression of CD34 (to evaluate vascularity) and Ki
      67 (as a proliferative index) in a variety of phaeochromocytomas and thus assess
      the utility of these markers as possible predictors of malignancy. PATIENTS AND
      METHODS: Deparaffinized tissue sections from 21 patients with benign and four
      with malignant phaeochromocytoma were assessed immunohistochemically to evaluate
      microvascular counts (using CD34 antigen) and the proliferative index (Ki-67
      antigen, monoclonal antibody MIB-1). RESULTS: There was no statistical
      association between high microvascular counts and malignancy, but there was
      between the MIB-1 score and malignancy (P < 0.001). CONCLUSIONS: A high MIB-1
      score in phaeochromocytoma suggests malignant behaviour in the component cells.
      The MIB-1 score may be a useful indicator for diagnosing malignant
      phaeochromocytoma.

PMID- 11251536
TI  - Proliferation and differentiation of prostatic stromal cells.
AB  - OBJECTIVES: To investigate the effects of androgen, transforming growth factor
      beta1 (TGF-beta) and basic fibroblast growth factor (bFGF) on the proliferation
      and differentiation of prostatic stromal cells of the dog in vivo and human
      stromal cells in vitro. MATERIALS AND METHODS: Twenty-two dogs had their serum
      concentration of testosterone and oestradiol determined by radioimmunoassay
      before and after castration. Light microscopy, transmission electron microscopy
      and an in situ cell-death assay were carried out successively before and after
      castration to evaluate prostatic histomorphology. A semi-quantitative reverse
      transcriptase-polymerase chain reaction (RT-PCR) was used to evaluate the
      expression of TGF-beta, bFGF and myosin in the canine prostate tissue after
      castration. In vitro serum-free cell cultures from human prostatic stroma were
      established and exposed to dihydrotestosterone (DHT), TGF-beta and bFGF in
      various concentrations. The proliferation of the cell cultures was detected by
      the tetrazolium assay. The differentiation from fibroblasts to smooth muscle
      cells (SMCs) was deduced by measuring the expression of SMC-specific proteins
      (myosin and smoothelin) using immunohistochemistry and RT-PCR. RESULTS:
      Castration resulted in a significant decrease in circulating testosterone levels
      (P < 0.01), but did not affect the circulating oestradiol levels (P > 0.05). The
      prostatic stromal cells, including SMCs and fibroblasts, diminished and underwent
      a serial pathological change of atrophy and apoptosis after castration. The
      atrophic cells were filled with intracellular lipofuscin. The expression of SMC
      myosin declined after castration, coincident with the increase in TGF-beta mRNA
      level and decline in bFGF mRNA. In vitro, TGF-beta inhibited the growth of human
      prostatic stromal cells during exponential growth, while enhancing myosin
      staining and stimulating the expression of smoothelin in confluent cultured
      stromal cells. bFGF stimulated the growth of the culture and inhibited the
      expression of smoothelin. DHT caused a weak increase in the proliferation and
      expression of SMC-specific proteins (P < 0.05). However, DHT and bFGF together
      stimulated the proliferation of stromal cells significantly more than either
      agent alone (P < 0.01). The combination of DHT and TGF-beta greatly enhanced the
      expression of SMC-specific proteins (P < 0.01), more strongly than either alone
      (P < 0.01). CONCLUSIONS: The whole prostate gland is an androgen-sensitive organ,
      with both the epithelium and stroma under the control of androgen. Androgen may
      direct the proliferation and differentiation of prostatic stromal cells by
      regulating the expression of TGF-beta and bFGF. Thus DHT, TGF-beta and bFGF may
      have important roles in regulating stromal cell homeostasis.

PMID- 11251537
TI  - Advanced glycation end-products are responsible for the impairment of corpus
      cavernosal smooth muscle relaxation seen in diabetes.
AB  - OBJECTIVE: To determine if advanced glycation end-products (AGEs) are responsible
      for the lower neuronal and endothelial-derived nitric oxide (NO)-mediated
      relaxation of corpus cavernosum in tissue in diabetic rats than in control rats.
      MATERIALS AND METHODS: Diabetes was induced in male Wistar rats by an
      intraperitoneal injection with streptozotocin (60 mg/kg). One group of diabetic
      rats was given free access to water and standard diet. A second group was given
      standard diet and aminoguanidine with their water (50 mg/100 mL) from the
      initiation of diabetes. Two groups of rats that were not diabetic acted as age
      matched controls. After 8 weeks animals were killed by cervical dislocation,
      corpus cavernosal tissue strips harvested and mounted in an organ bath to measure
      isometric tension. After 90 min of equilibration at optimal resting tension and
      contraction with 1 micromol/L noradrenaline, the response to either acetylcholine
      or electrical field stimulation (EFS) after adding guanethidine (5 micromol/L)
      and atropine (1 micromol/L) was determined for each group. RESULTS: There was no
      difference between the baseline characteristics of all the experimental groups.
      After 8 weeks the mean body mass and glycosylated haemoglobin (HbA1c) were
      significantly greater in the diabetic than in control animals. Aminoguanidine had
      no effect on the recorded body mass or HbA1c. The in vitro relaxation response to
      the application of acetylcholine or EFS of tissue strips from age-matched control
      animals fed a standard diet and those supplemented with aminoguanidine were the
      same. The administration of aminoguanidine to diabetic animals for 8 weeks
      reversed the expected impaired relaxation response to acetylcholine; the response
      to EFS was similar. CONCLUSION: AGEs are more prevalent in erectile tissue from
      diabetic than in control animals. Aminoguanidine reversed the impairment in
      neuronal and endothelial NO-mediated penile smooth muscle relaxation seen in
      diabetes. As aminoguanidine prevents AGE formation, erectile dysfunction in
      diabetes is probably caused partly by the generation of AGEs.

PMID- 11251539
TI  - Robotically-assisted laparoscopic radical prostatectomy.

PMID- 11251538
TI  - Nitric oxide-mediated corpus cavernosal smooth muscle relaxation is impaired in
      ageing and diabetes.
AB  - OBJECTIVE: To examine nitric-oxide (NO)-mediated relaxation in cavernosal smooth
      muscle in a rat model of diabetes, as previous experiments showed that HbA1c (an
      isoform of glycosylated haemoglobin and a marker of long-term diabetic control)
      impaired NO-mediated relaxation of normal corpus cavernosal tissue through the
      generation of superoxide anions. MATERIALS AND METHODS: Eight weeks after the
      induction of diabetes, male Wistar rats were killed and cavernosal tissue
      obtained. Strips were contracted with 1 micromol/L noradrenaline before applying
      acetylcholine or electrical field stimulation (EFS) or sodium nitroprusside
      (SNP). Relaxation responses were repeated in the presence of L-arginine (100
      micromol/L), indomethacin (10 micromol/L) or superoxide dismutase (SOD, 120
      IU/mL). Young and age-matched control animals were examined in the same way.
      RESULTS: Eight weeks of uncontrolled diabetes caused a significant impairment in
      mean relaxation responses to acetylcholine (P < 0.05) and to EFS (P < 0.05), but
      not to SNP, compared with young and age-matched controls, respectively. L
      arginine, indomethacin and SOD had no significant effect on this impairment.
      Ageing caused a lesser but significant impairment in EFS-mediated cavernosal
      smooth muscle relaxation (P < 0.05). CONCLUSION: Diabetes impairs endothelial and
      neuronal NO-mediated cavernosal smooth muscle relaxation in rats in vitro. This
      effect is not mediated by an alteration in the intracellular action of NO, the
      availability of NO, superoxide anion inactivation of NO or the generation of
      constrictor prostanoids. It is possible that cholesterol or advanced glycation
      end products are responsible for the effect of diabetes on penile smooth
      function.

PMID- 11251540
TI  - Urethral wands for impotence.

PMID- 11251541
TI  - Clear cell adenocarcinoma of the female urethra showing strong immunostaining for
      prostate-specific antigen.

PMID- 11251542
TI  - Tumour of the spermatic cord: an unusual primary manifestation of an epithelial
      mesothelioma of the peritoneum with patent processus vaginalis.

PMID- 11251543
TI  - Paediatric urinary tract infection and the necessity of complete urological
      imaging.

PMID- 11251544
TI  - Congenital megaprepuce: an emerging condition--how to recognize and treat it.

PMID- 11251545
TI  - Whewellite, weddellite and company: where do all the strange names originate?

PMID- 11251546
TI  - The use of scrotal ultrasonography in male infertility.

PMID- 11251547
TI  - A urethral duplication cyst complicated by a squamous cell carcinoma.

PMID- 11251550
TI  - Antibiotics in acne: time for a rethink.

PMID- 11251551
TI  - Thalidomide.

PMID- 11251552
TI  - Skin and oral fibroblasts exhibit phenotypic differences in extracellular matrix
      reorganization and matrix metalloproteinase activity.
AB  - BACKGROUND: Oral mucosal wounds are characterized by rapid re-epithelialization
      and remodelling. In vitro, oral mucosal fibroblasts exhibit a fetal phenotype
      with increased extracellular matrix reorganizational ability, migration and
      experimental wound repopulation when compared with skin fibroblasts. OBJECTIVES:
      To investigate whether phenotypic differences in the expression and production of
      matrix metalloproteinase (MMP) -2 and tissue inhibitors of metalloproteinases
      (TIMPs) could play an important part in mediating these in vitro differences.
      METHODS: Skin and oral mucosal fibroblast MMP-2, TIMP-1 and TIMP-2 mRNA
      expression and protein production were studied in three-dimensional collagen
      lattices using quantitative competitive reverse transcriptase-polymerase chain
      reaction (QCRT-PCR), enzyme-linked immunosorbent assay (ELISA), zymography and
      reverse zymography. RESULTS: Oral mucosal fibroblasts exhibited increased levels
      of the 62-kDa active form of MMP-2 and lattice contraction when compared with
      skin fibroblasts. Oral mucosal and skin fibroblast MMP-2 gene expression and
      synthesis of the 72-kDa pro-MMP-2 was similar as assessed by QCRT-PCR, zymography
      and ELISA. Differential MMP-2 activation was, however, related to phenotypic
      differences in TIMP activity between the skin and oral mucosal fibroblasts, as
      assessed by reverse zymography. CONCLUSIONS: These studies propose a mechanism by
      which fibroblast phenotype may contribute directly to the observed preferential
      remodelling of oral wounds.

PMID- 11251553
TI  - Epidermal interleukin-1 alpha generation is amplified at low humidity:
      implications for the pathogenesis of inflammatory dermatoses.
AB  - BACKGROUND: We have previously reported that low humidity amplifies the
      hyperproliferative and inflammatory response to barrier disruption. Other reports
      suggest that epidermal interleukin (IL)-1 alpha is stimulated by various factors
      related to epidermal inflammation and that it may induce other proinflammatory
      molecules. OBJECTIVES: To evaluate the generation of IL-1 alpha in the skin of
      hairless mice kept under various conditions of environmental humidity. METHODS:
      We carried out an immunohistochemical study, and evaluated epidermal IL-1 alpha
      mRNA and protein levels, and release of IL-1 alpha from skin after tape
      stripping, in hairless mice kept under low or high humidity. RESULTS: The
      immunohistochemical study showed that the amount of IL-1 alpha in the epidermis
      was higher in animals kept in a low-humidity environment than in a high-humidity
      one. The epidermal IL-1 alpha mRNA and protein levels increased significantly
      when the animals were kept under low humidity. Moreover, the release of IL-1
      alpha from skin immediately after tape stripping was significantly higher in
      animals kept in a low-humidity environment than in a high-humidity one.
      CONCLUSIONS: These results suggest that IL-1 alpha is an important factor in
      mediating the relationship between environmental humidity and epidermal
      pathology.

PMID- 11251554
TI  - Effects of fat cells on keratinocytes and fibroblasts in a reconstructed rat skin
      model using collagen gel matrix culture.
AB  - BACKGROUND: Fat cells (stromal tissue cells), not only have the function of lipid
      metabolism, but produce various cytokines that exert an influence on other cell
      types through paracrine or endocrine mechanisms. OBJECTIVES: To elucidate
      possible roles of fat cells in the skin, we examined their effects on the
      biological behaviour of keratinocytes and dermal fibroblasts in culture. METHODS:
      In the present study, focusing upon fat cell--keratinocyte or fat cell--dermal
      fibroblast interactions, we used a reconstructed skin system with rat skin cells
      in a three-dimensional collagen gel matrix culture. RESULTS: In this coculture
      system, fat cells promoted the proliferation and differentiation of
      keratinocytes. When keratinocytes were seeded directly on the fat cell layer
      without dermal fibroblasts, they proliferated extensively and formed a thick
      epidermal layer with a well-differentiated structure. Conversely, fat cells
      inhibited the proliferation of dermal fibroblasts. These effects of fat cells
      were presumed to be mediated by cytokines derived from the fat cells.
      CONCLUSIONS: The effects of fat cells could not be mimicked by the addition of
      leptin, tumour necrosis factor-alpha or insulin-like growth factor-II, suggesting
      that fat cells are mediating these activities via some other cytokines.

PMID- 11251555
TI  - Immunohistochemical studies on proteoglycan expression in normal skin and chronic
      ulcers.
AB  - BACKGROUND: Proteoglycans (PGs) represent a large family of complex molecules.
      They are found either as integral membrane components or constituents of the
      extracellular matrix. Their protein backbones are linked to different
      glycosaminoglycans, such as dermatan-, chondroitin-, keratan- or heparan
      sulphate. The molecules have specific functions during developmental processes as
      well as in diseases, such as cancer and inflammation. OBJECTIVES: The expression
      patterns of various cell-associated heparan and chondroitin/dermatan-sulphate PGs
      in human skin and chronic venous ulcers were investigated. METHODS: Tissue
      sections from 11 patients with chronic venous ulcers were used in this study.
      Monoclonal antibodies were used for detection of the proteoglycans syndecan-1, -2
      and -4, glypican, CD44 and perlecan. RESULTS: The different PGs exhibited
      individual staining patterns. Syndecan-1 and -4 and glypican expression in
      chronic ulcers differed from the staining in normal skin. Whereas the expression
      of syndecan-4 and glypican in intact skin was mostly in the pericellular regions
      of keratinocytes, the epidermal cells from the wound edge contained mostly
      intracellular PGs. In the wound edge, syndecan-4 was predominantly expressed by
      epidermal basal layer cells. Syndecan-1 was less expressed at the epidermal wound
      margins. PGs bind growth factors, regulate proteolytic activity and act as matrix
      receptors. CONCLUSIONS: The altered expression patterns of glypican and syndecan
      1 and -4 in chronic ulcers reflect their possible roles during inflammation and
      cell proliferation. Hence, analysis of PG expression should be of interest in
      future studies on normal as well as defective wound healing.

PMID- 11251556
TI  - Treatment with 815-nm diode laser induces long-lasting expression of 72-kDa heat
      shock protein in normal rat skin.
AB  - BACKGROUND: We previously reported that skin closure is improved by
      photoirradiation of the wound margins with an 815-nm diode laser system.
      OBJECTIVES: To determine whether the beneficial effects of laser treatment
      involve the overexpression of the inducible 72-kDa heat shock protein, Hsp70.
      METHODS: Expression of Hsp70 was investigated by immunocytochemistry in normal
      hairless rat dorsal skin and compared with its expression after laser
      photoirradiation. RESULTS: Constitutive expression of Hsp70 was mainly confined
      to the upper epidermal layer. Laser irradiation further increased epidermal
      expression of Hsp70 while inducing de novo synthesis of the protein in dermal
      structures, particularly around blood vessels, hair follicles and sebaceous
      glands. Laser-induced expression of Hsp70 was still present 7 days after
      photoirradiation. CONCLUSIONS: Laser-induced expression of Hsp70 might contribute
      to improved tissue regeneration and wound healing.

PMID- 11251557
TI  - The effects of topical alpha-hydroxyacids on the normal skin barrier of hairless
      mice.
AB  - BACKGROUND: alpha-hydroxyacids (AHA), such as glycolic acid and lactic acid, have
      recently been used in cosmetic and dermatological formulations. However, the
      mechanisms of action of these substances have not been well documented.
      OBJECTIVES: This study was done to investigate the effects of AHA on the skin
      barrier of hairless mice and to clarify the contribution of AHA to the formation
      and secretion of the lamellar bodies (LB), which are known to be the critical
      structure for barrier function in the epidermis. METHODS: 5% Lactic acid and 5%
      glycolic acid were applied to normal skin of the mice daily for 14 days. RESULTS:
      Changes in transepidermal water loss (TEWL), capacitance and electron microscopic
      findings of the epidermis of hairless mice were compared with those in which only
      the vehicle was applied. CONCLUSIONS: There were no significant differences in
      TEWL, capacitance or epidermal thickness between the epidermis of the mice to
      which AHA or vehicle only had been applied. On electron micrographs, the normal
      epidermis to which AHA had been applied showed an increase in the number and
      secretion of LB and a decrease in the number of stratum corneum (SC) layers in
      comparison with the epidermis to which the vehicle only had been applied. The
      lipid layers of the SC intercellular spaces and calcium gradient in both the
      epidermis with application of AHA and that with vehicle only were normal. These
      results suggest that AHA, in low concentration (5%), may improve the skin barrier
      in hairless mice by inducing enhanced desquamation, and by increasing the number
      and secretion of LB without increasing TEWL.

PMID- 11251558
TI  - Killing of cutaneous microbial species by photodynamic therapy.
AB  - BACKGROUND: Photodynamic therapy (PDT) utilizes photosensitizers and light.
      Whereas PDT use in cancer treatment has been widely accepted, antimicrobial PDT
      (APDT) is still in its early stages of development. OBJECTIVES: To study
      microbial killing in vitro using APDT. METHODS: We used a combination of
      methylene blue and visible light, and a range of microbial species representative
      of those encountered on the skin in health and disease. Using standard light
      intensity conditions (slide projector, 25 cm distance from target, 42 mW cm(-2))
      and methylene blue dye at 100 microg mL(-1), kill rates and subsequent D-values
      were determined against Staphylococcus aureus, S. epidermidis, Streptococcus
      pyogenes, Corynebacterium minutissimum, Propionibacterium acnes and Candida
      albicans. RESULTS: D-values for these species were 72, 66, 48, 120, 30 and 660 s,
      respectively. The effects of light intensity on the killing of S. epidermidis
      showed the kill rate to be proportional to the light intensity. A high rate of
      cell kill was also obtained using natural sunlight. CONCLUSIONS: Overall, these
      results indicate that APDT of the skin may represent a useful alternative to
      conventional antimicrobial treatment.

PMID- 11251559
TI  - Evaluation of the use of tyrosinase-specific and melanA/MART-1-specific reverse
      transcriptase-coupled--polymerase chain reaction to detect melanoma cells in
      peripheral blood samples from 299 patients with malignant melanoma.
AB  - BACKGROUND: There is a current need for a reliable prognostic marker for melanoma
      patients, particularly those with stage 2 and stage 3 disease, so that adjuvant
      therapies can be directed appropriately. OBJECTIVES: To establish whether or not
      the use of tyrosinase-specific or melanA/MART-1-specific reverse transcriptase
      coupled-polymerase chain reaction (RT--PCR) of peripheral blood cells detects
      preclinical disease progression in patients with malignant melanoma. METHODS: Two
      hundred and ninety-nine patients with melanoma in clinical stages 1--4 were
      observed in this study. Samples were obtained sequentially from 153 of these
      patients at 4-week intervals over a period of up to 2 years and correlated with
      clinical evidence of disease activity. Tyrosinase and melanA/MART-1 amplicons
      were analysed by agarose gel electrophoresis and Southern blot hybridization
      subsequent to a single round of amplification. RESULTS: We demonstrated a
      statistically significant increase in tyrosinase RT--PCR positivity with
      advancing stage of melanoma progression. The percentage tyrosinase positivity in
      910 samples tested was: stage 1, 135 samples, 34% positive; stage 2, 196 samples,
      51% positive; stage 3, 423 samples, 50% positive; and stage 4, 156 samples, 65%
      positive. The positivity rate for individual patients tested sequentially was
      higher if only one positive test was required to label a patient positive, at
      42%, 65%, 82% and 81% for patients in stages 1--4, respectively. However, we did
      not find a clear pattern of conversion from negativity to positivity in patients
      who progressed during the study from stage 2 to stage 3 or stage 3 to stage 4,
      and found no clear evidence of increased positivity rates in the 6-week period
      following melanoma-related surgery in patients with stage 3 and 4 disease. The
      positivity rate for melanA/MART-1 was lower for both patients and samples, and no
      melanA/MART-1-positive sample was negative for tyrosinase. CONCLUSIONS: We
      conclude that the presence of circulating tyrosinase-positive cells as detected
      by this method appears to be a discontinuous rather than a continuous phenomenon,
      even in patients with stage 4 disease. For this reason the assay cannot be
      recommended as a method of sequentially monitoring individual patients in a
      clinical setting.

PMID- 11251560
TI  - Quantity of sunscreen used by European students.
AB  - BACKGROUND: The ability of sunscreen products to delay sun-induced skin erythema
      is indicated by the sun protection factor (SPF), which is measured using an
      internationally agreed sunscreen thickness of 2 mg cm(-2). OBJECTIVES: To
      determine the thickness of sunscreen used under practical conditions. METHODS: In
      two double-blind randomized trials performed in five different places in Europe
      in 1997 and 1998, 148 18--24-year-old students received either an SPF 10 or an
      SPF 30 sunscreen to be used during their summer holidays. RESULTS: Complete,
      detailed data on quantities of sunscreen used and skin areas on to which
      sunscreen was applied were available for 124 students. The median thickness of
      sunscreen applied was 0.39 mg cm(-2). We found no variation in sunscreen
      thickness according to sex, skin phototype, study place or SPF. CONCLUSIONS: Our
      results indicate that most consumers do not benefit from the SPF indicated on
      sunscreen bottles, and do not support the idea that thickness of sunscreen
      applied would be greater if these products were cheaper. We suggest that
      information on ability of a sunscreen product to prevent sunburn should be
      adapted in order to reflect actual usage patterns.

PMID- 11251561
TI  - Lymphocytic infiltration of the skin is a photosensitive variant of lupus
      erythematosus: evidence by phototesting.
AB  - BACKGROUND: Lymphocytic infiltration of the skin (LIS) is a disorder in which
      photosensitivity has been suspected but never proven. OBJECTIVES: To carry out a
      systematic photobiological investigation in patients with LIS and to compare the
      photobiological features of LIS with those of other photosensitive disorders.
      METHODS: We performed provocative phototesting with ultraviolet (UV) A and UVB in
      10 patients with active LIS. RESULTS: In all patients, UVA and/or UVB elicited
      abnormal papular phototest reactions resembling lesions of LIS both clinically
      and histologically. Lesions typically developed 3--6 days (mean +/- SD 100.8 +/-
      20.9 h) after the first UV exposure. CONCLUSIONS: This characteristic latency
      interval together with certain clinical features, i.e. onset in summer,
      predilection for the face and persistence of the lesions, indicate that LIS is a
      photosensitive disorder distinct from polymorphic light eruption but indistinct
      from lupus erythematosus (LE). Both our photobiological findings and the
      effective treatment with hydroxychloroquine in half of our patients strengthen
      the proposal that the two entities LIS and LE tumidus are identical. As diagnosis
      cannot be made by histological, immunofluorescence or laboratory criteria,
      provocative phototesting may be a diagnostic aid in this disorder.

PMID- 11251562
TI  - Hair density, hair diameter and the prevalence of female pattern hair loss.
AB  - BACKGROUND: Female pattern hair loss is common but estimates of its prevalence
      have varied widely. The relationships between the clinical diagnosis of female
      pattern hair loss and objective measurements of hair density and hair diameter
      have not previously been evaluated. OBJECTIVES: To determine the prevalence of
      female pattern hair loss and to relate the clinical findings to hair density and
      hair diameter. METHODS: We examined 377 women, aged 18--99 years, who presented
      to a general dermatology clinic with complaints unrelated to hair growth (the
      unselected sample). A second group of 47 women referred with typical female
      pattern hair loss was included in analyses of the relationships between hair
      density, hair diameter and the clinical diagnosis. Hair density was measured
      using a photographic method. In each subject the major and minor axis diameters
      were measured in a random sample of 50 hairs. RESULTS: Six per cent of women aged
      under 50 years were diagnosed as having female pattern hair loss, increasing to
      38% in subjects aged 70 years and over. The mean +/- SEM hair density was 293 +/-
      61.3 hairs cm(-2) at age 35 years, falling to 211 +/- 55.1 hairs cm(-2) at age 70
      years. Hair density showed a normal distribution in the unselected sample. Most
      women classified as having female pattern hair loss had hair densities within the
      lower half of the normal distribution. The perception of hair loss was determined
      mainly by low hair density (ANOVA P < 0.001), but there was overlap in hair
      density between women classified as having Ludwig I hair loss and the no hair
      loss group, which was partly accounted for by differences in mean hair diameter
      (ANOVA P < 0.001). Low hair density was associated with fewer hairs of all
      diameters. CONCLUSIONS: Hair density in women is distributed as a normal
      variable, indicating that it is determined as a multifactorial trait. Women with
      female pattern hair loss have a hair density which falls below the mean but lies
      within the spectrum of the normal distribution, although other factors, including
      hair diameter, may affect the subjective impression of hair loss. The hair
      diameter data suggest that low hair density is not due to progressive diminution
      in hair follicle size and that follicular miniaturization may occur within the
      space of a single hair cycle.

PMID- 11251563
TI  - Use of a wrist activity monitor for the measurement of nocturnal scratching in
      patients with atopic dermatitis.
AB  - BACKGROUND: The amount of nocturnal scratching can be an indirect correlate of
      itch in pruritic dermatoses. We have previously used an infrared video camera to
      measure nocturnal scratching in atopic dermatitis (AD). Although this is a
      reliable method of measuring nocturnal scratching, it is not suitable for routine
      monitoring in clinical use. OBJECTIVES: To find a simplified way of monitoring
      itch. METHODS: We tried using a wrist activity monitor (ActiTrac) for the
      measurement of nocturnal scratching in patients with AD. ActiTrac is a wristwatch
      shaped device that contains a piezoceramic sensor to measure and record limb
      movement over a pre-set time interval. The acceleration signal produced by motion
      of the hands is stored and downloaded into a personal computer. The average value
      of acceleration (AVA, 10(-3) g min(-1)) was calculated and compared with total
      scratching time as a percentage of total recording time (TST%) measured with the
      use of an infrared video camera in 63 recordings of 21 patients with AD. For 261
      recordings in 29 patients with AD, the AVA was measured and correlated with
      disease severity, and compared with the AVA of five non-itchy controls. RESULTS:
      There was a significant correlation between the AVA and TST% (r = 0.91, P <
      0.001), and a regression equation of y = 0.44x - 2.5 was obtained. The AVA
      correlated well with the severity of AD and definitely differed from the results
      observed in normal controls. The AVA (mean +/- SD) was 44.4 +/- 19.1 for 115
      recordings in patients with severe AD, 23.2 +/- 10.9 for 89 recordings in
      patients with moderate AD, 8.9 +/- 6.0 for 57 recordings in patients with mild AD
      and 4.1 +/- 1.9 for 25 recordings in five normal controls. The units used here
      are arbitrary units min-1 with a range of 0--250, which corresponds to 0-75 x 10(
      6) g min(-1). CONCLUSIONS: A wrist activity monitor is able to measure nocturnal
      scratching. However, further methods of analysis should be sought to select
      scratching activity exclusively.

PMID- 11251564
TI  - Thalidomide usage in Wales: the need to follow guidelines.
AB  - BACKGROUND: Thalidomide is a potentially useful drug for several dermatological
      disorders. OBJECTIVES: To assess prescribing and monitoring practices for this
      drug in Wales. METHODS: A questionnaire was completed by 17 of 19 consultant
      dermatologists concerning thalidomide usage in Wales (population 2.93 million).
      RESULTS: Eleven of the 17 respondents had used thalidomide in 40 patients. Only
      two consultants gave information leaflets and only five obtained written consent.
      Four obtained baseline nerve conduction studies and nine obtained these during
      therapy. Of seven women of child-bearing age currently taking thalidomide, none
      had had baseline pregnancy tests. CONCLUSIONS: We describe variability in
      prescribing practices for thalidomide. Published guidelines are reviewed and
      suggestions made concerning consent forms, pregnancy testing, nerve conduction
      studies and patient information.

PMID- 11251565
TI  - In vitro drug allergy detection system incorporating human liver microsomes in
      chlorazepate-induced skin rash: drug-specific proliferation associated with
      interleukin-5 secretion.
AB  - BACKGROUND: Chlorazepate is a benzodiazepine often used for pre-operative
      anxiolysis. The central metabolite responsible for the pharmacological and
      probably for the adverse effects of most benzodiazepines, including chlorazepate,
      is N-desmethyldiazepam. We report a woman who developed a generalized exanthem 1
      day after receiving chlorazepate and four other drugs related to anaesthesia for
      surgery of the larynx. Patch tests pointed to chlorazepate as the culprit drug
      for the skin rash. OBJECTIVES: The purpose of this study was to detect drug
      allergy to chlorazepate or a metabolite in vitro by means of the lymphocyte
      transformation test (LTT), and to determine the concentrations of the T-helper
      (Th) 2-type cytokine interleukin (IL)-5 and the Th1-type cytokine interferon
      (IFN) -gamma in the culture supernatants. METHODS: We performed an LTT with
      peripheral blood mononuclear cells from the patient and a control, employing
      human liver microsomes containing cytochrome P450 enzymes as a metabolizing
      system, in parallel cultures. IL-5 and IFN-gamma concentrations in the culture
      supernatants were assessed by enzyme-linked immunosorbent assay. RESULTS: In the
      LTT, no T-cell reactivity was observed to the parent compound chlorazepate,
      whereas coincubation of the drug with human liver microsomes yielded
      proliferative T-cell reactivity, which was associated with secretion of IL-5 but
      not of IFN-gamma. CONCLUSIONS: We conclude that addition of a metabolizing system
      may be advantageous for in vitro detection of T-cell reactivity to drug
      metabolites in the LTT.

PMID- 11251566
TI  - A randomized comparison of 4 weeks of terbinafine vs. 8 weeks of griseofulvin for
      the treatment of tinea capitis.
AB  - BACKGROUND: Tinea capitis is a common childhood infection that has recently
      become more frequent in urban areas in Europe and the U.S.A. The current licensed
      treatment in children is griseofulvin 10 mg kg(-1) daily, which is usually given
      for 6--8 weeks. OBJECTIVES: To compare this treatment with a 4-week course of
      oral terbinafine. METHODS: Terbinafine was given at the following doses: in
      children weighing < 20 kg, 62.5 mg daily; 20--40 kg, 125 mg daily; > 40 kg, 250
      mg daily. Two hundred and ten children aged 2--16 years, with mycologically
      confirmed tinea capitis, were randomized to 4 weeks treatment with terbinafine or
      8 weeks with griseofulvin, and followed for a total of 24 weeks to determine the
      difference between treatments with respect to short- and long-term efficacy and
      tolerability. RESULTS: One hundred and forty-seven patients were evaluable
      (terbinafine 77, griseofulvin 70). Although the 4-week course of terbinafine
      resulted in a trend to more rapid clearance of tinea capitis, there were no
      statistically significant differences between the two drugs in terms of overall
      outcome or tolerability, apart from in a subgroup of patients with Trichophyton
      infections, and weighing > 20 kg, who responded better to terbinafine than to
      griseofulvin at 4 weeks. By contrast, there was a better response to griseofulvin
      than to terbinafine in patients with Microsporum audouinii infections.
      CONCLUSIONS: Overall, the study showed that 4 weeks of treatment with oral
      terbinafine has similar efficacy to 8 weeks of treatment with griseofulvin for
      the management of tinea capitis in children.

PMID- 11251567
TI  - Evaluating a telemedicine system to assist in the management of dermatology
      referrals.
AB  - BACKGROUND: Teledermatology systems fall into two categories: live video or store
      and-forward. In the former, video-conferencing equipment is used to connect a
      patient with a remote consultant. This method has been evaluated as an aid to
      dermatology, but it is expensive both in terms of capital and running costs.
      Video consultations are generally longer than conventional ones and harder to
      schedule. Some authors have considered store-and-forward as an alternative to
      live video: instead of a consultation, specialists could make a rapid inspection
      of a transmitted still image. OBJECTIVES: A study was conducted to evaluate the
      role of telemedicine in the dermatology outpatients department of a district
      general hospital (Whittington Hospital NHS Trust, London, U.K.). METHODS: One
      hundred and ninety-four patients were seen by one of two consultant
      dermatologists. A nurse used a video camera to store digital images of each
      patient's problem and compiled a history from the GP's referral letter. The
      images were reviewed 13 months later by both dermatologists; they recorded a
      provisional diagnosis and an assessment of how urgent an appointment would have
      been made given the information provided by the system. A third consultant graded
      the level of agreement between the telemedicine diagnoses and the face-to-face
      consultations. RESULTS: High levels of agreement were found between the diagnoses
      of the dermatologists using the system to inspect images and those of the
      dermatologist who saw the patients (77%). Consultants using the system
      recommended fewer urgent appointments (32% compared with 64%) and felt that in
      31% of cases the patient did not need to be seen. In 15% of these cases (5% of
      the total), however, their diagnosis differed significantly from that of the
      consultant who saw the patient. Had the system been in use, 14% of patients
      conventionally assigned a non-urgent appointment would have been seen urgently.
      CONCLUSIONS: The images allowed a reasonably accurate diagnosis. The software was
      not reliable (six cases could not be viewed), or easy to use (it took
      approximately an hour to view 20 cases) but an improved version could be used in
      triaging outpatient appointments.

PMID- 11251568
TI  - Familial clustering of polymorphic light eruption in relatives of patients with
      lupus erythematosus: evidence of a shared pathogenesis.
AB  - BACKGROUND: Abnormal photosensitivity is a common feature of many forms of lupus
      erythematosus (LE). OBJECTIVES: To examine the role of polymorphic light eruption
      (PLE) as a possible predisposing factor for cutaneous forms of LE. METHODS:
      Eighty-five patients with well-characterized subacute cutaneous LE (SCLE) and
      discoid LE (DLE) were recruited from outpatient clinics, and the prevalence of
      PLE determined by detailed interview and clinical examination. RESULTS: Symptoms
      consistent with PLE were reported in 61% and 55% of SCLE and DLE patients,
      respectively; this was significantly higher than the overall population
      prevalence of 13.6% (P < 0.001), giving a relative risk (RR) for PLE in SCLE
      patients of 3.37 (95% confidence interval, CI 2.46--4.28) and DLE patients of
      3.11 (95% CI 2.31--3.91). PLE developed before the onset of LE in 61% of cases
      (median interval 12 years, range 1--40), concomitantly in 24%, and subsequently
      in a further 15% (median interval 3.5 years, range 1--25). To delineate the
      relationship between PLE and LE further, the prevalence of PLE was determined in
      103 otherwise unaffected first-degree relatives of SCLE and DLE probands; we had
      previously demonstrated clustering of PLE in families, reflecting a strong
      genetic component. We found a significantly higher PLE prevalence in relatives of
      the LE probands than in the general population (P < 0.001), giving an RR for PLE
      of 2.29 (95% CI 1.55--3.03) and 2.61 (95% CI 1.32--3.89) for female and male
      relatives, respectively. CONCLUSIONS: The high prevalence of PLE in LE patients,
      together with clustering of PLE among first-degree relatives of SCLE and DLE
      probands, suggests that there may be a shared pathogenetic basis for PLE and
      cutaneous LE. We propose that predisposition to PLE may contribute to the LE
      phenotype in otherwise susceptible individuals.

PMID- 11251569
TI  - Phenotypic and genotypic characterization of antibiotic-resistant
      Propionibacterium acnes isolated from acne patients attending dermatology clinics
      in Europe, the U.S.A., Japan and Australia.
AB  - BACKGROUND: Propionibacterium acnes is the target of antimicrobial treatments for
      acne vulgaris. Acquired resistance to erythromycin, clindamycin and tetracyclines
      has been reported in strains from diverse geographical loci, but the molecular
      basis of resistance, via mutations in genes encoding 23S and 16S rRNA,
      respectively, has so far only been elucidated for isolates from the U.K.
      OBJECTIVES: To determine whether similar or different resistance mechanisms occur
      in resistant P. acnes isolates from outside the U.K. METHODS: The phenotypes and
      genotypes of 73 antibiotic-resistant strains of P. acnes obtained from the skin
      of acne patients in the U.K., U.S.A., France, Germany, Australia and Japan were
      compared. Antibiotic susceptibilities were determined by minimum inhibitory
      concentration (MIC) measurements, and polymerase chain reaction and DNA
      sequencing were used to identify mutations in genes encoding rRNA. RESULTS: Most
      erythromycin-resistant isolates (MIC(90) > or = 512 microg mL(-1)) were cross
      resistant to clindamycin but at a much lower level (MIC(90) > or = 64 microg mL(
      1)). As in the U.K., resistance to erythromycin was associated with point
      mutations in 23S rRNA in 49 of 58 strains. An A-->G transition at Escherichia
      coli equivalent base 2058 was present in 24 strains. This gave a unique cross
      resistance phenotype against a panel of macrolide, lincosamide and type B
      streptogramin antibiotics. Two further point mutations (at E. coli equivalent
      bases 2057 and 2059) were identified (in three and 22 isolates, respectively) and
      these were also associated with specific cross-resistance patterns originally
      identified in isolates from the U.K. However, nine of 10 erythromycin resistant
      strains from Germany did not exhibit any of the three base mutations identified
      and, in six cases, cross-resistance patterns were atypical. Consistent with
      previous U.K. data, 34 of 38 tetracycline-resistant strains carried a base
      mutation at E. coli 16S rRNA equivalent base 1058. Tetracycline-resistant
      isolates displayed varying degrees of cross-resistance to doxycycline and
      minocycline, but isolates from the U.S.A. had higher MICs for minocycline (4--16
      microg mL(-1)) than isolates from other countries and, in particular, Australia.
      All the P. acnes isolates resistant to one or more of the commonly used antiacne
      antibiotics were sensitive to penicillin, fusidic acid, chloramphenicol and the
      fluoroquinolone, nadifloxacin. All but one isolate (from the U.K.) were sensitive
      to trimethoprim. CONCLUSIONS: This study shows that 23S and 16S mutations
      identified in the U.K. conferring antibiotic resistance in P. acnes are
      distributed widely. However, resistant strains were isolated in which mutations
      could not be identified, suggesting that as yet uncharacterized resistance
      mechanisms have evolved. This is the first report of high-level resistance to
      minocycline and is of concern as these strains are predicted to be clinically
      resistant and are unlikely to remain confined to the U.S.A. Epidemiological
      studies are urgently required to monitor how resistant strains are selected, how
      they spread and to ascertain whether the prevalence of resistance correlates with
      antibiotic usage patterns in the different countries.

PMID- 11251570
TI  - Changing frequency of thiuram allergy in healthcare workers with hand dermatitis.
AB  - BACKGROUND: Healthcare workers (clinical, allied/paramedical professions and
      ancillary workers) may have prolonged contact with natural rubber latex devices,
      particularly in the form of natural rubber latex gloves. OBJECTIVES: To examine
      the changing frequency of type IV thiuram allergy in healthcare workers with hand
      dermatitis over a 16-year period. METHODS: During the study period, 450
      healthcare workers (352 women and 98 men) with hand dermatitis were investigated,
      and their patch test results were analysed retrospectively. RESULTS: On average,
      a thiuram-positive patch test was noted in 12% of individuals, with a peak
      incidence of 27% of the patients patch tested in 1994. Comparison of results
      between 1983--88 and 1989--93 showed a statistically significant increase in the
      incidence of thiuram-positive patch tests (odds ratio 2.55, 95% confidence
      interval 1.25--5.20, P = 0.01). CONCLUSIONS: We have documented a changing
      frequency of thiuram-positive patch tests in healthcare workers with hand
      dermatitis since 1983. This may reflect changes in degree of exposure to thiurams
      in medical gloves during this period.

PMID- 11251571
TI  - Lymphomatoid papulosis in children: a study of 10 children registered by the
      Dutch Cutaneous Lymphoma Working Group.
AB  - Lymphomatoid papulosis (LyP) is a chronic recurrent self-healing condition, with
      histological features suggestive of a malignant lymphoma. Only a few cases have
      been described in children. We report 10 children with this skin disease and
      compare them with the adult type of LyP and childhood cases described in the
      literature. Although LyP has the same clinical picture and histology in both age
      groups, in contrast with the adult type no transformation into malignancy has
      been described in childhood.

PMID- 11251572
TI  - Nodular and bullous cutaneous mastocytosis of the xanthelasmoid type: case
      report.
AB  - Severe generalized nodular and bullous mastocytosis of the xanthelasmoid type is
      described in a 7-month-old boy. Reddish to yellowish-brown xanthelasmoid papules
      and nodules first developed in the inguinal region a few weeks after birth and
      then progressively spread to cover nearly the entire body surface. There was
      severe pruritus and recurrent episodes of blistering. The diagnosis of cutaneous
      mastocytosis of the xanthelasmoid type with subepidermal bullae was confirmed by
      skin biopsies showing solid and deeply penetrating infiltrates of metachromatic
      mast cells under light and electron microscopy. Systemic involvement of other
      organs, however, was excluded by bone scintigraphy, abdominal ultrasound, bone
      marrow aspiration and echocardiography. The extensive skin involvement was
      reflected in highly elevated urinary levels of histamine (263.4 microg L(-1)) and
      its metabolite N-methylimidazole acetic acid (20.8 mg L(-1)). The patient was
      systematically well and received only symptomatic treatment. Over a period of 1
      year, the condition gradually improved, and the skin lesions began to flatten and
      regress.

PMID- 11251573
TI  - Scleromyxedema (lichen myxedematosus) associated with dermatomyositis.
AB  - A 41-year-old white man is described with papules of the lower and upper back,
      the neck and the upper chest, a marked deposition of mucin in the upper reticular
      dermis, and an IgG lambda monoclonal gammopathy strongly evocative of
      scleromyxedema (lichen myxedematosus). Additionally, he developed intense
      myalgia, muscle weakness and rhabdomyolysis, which were associated with
      heliotrope erythema, photosensitivity and an erythematous rash of the dorsum of
      the hands with Gottron's papules. Muscle biopsy revealed an inflammatory
      myositis, and dermatomyositis was diagnosed. The association of dermatomyositis
      and secondary mucinosis, or muscle involvement in primary papular mucinosis are
      not rare. However, the association between scleromyxedema and dermatomyositis has
      only exceptionally been reported.

PMID- 11251574
TI  - A new case of alpha-N-acetylgalactosaminidase deficiency with angiokeratoma
      corporis diffusum, with Meniere's syndrome and without mental retardation.
AB  - alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency is a rare hereditary
      lysosomal storage disease, and only three alpha-NAGA-deficient patients with
      angiokeratoma corporis diffusum (Kanzaki) have been described. We report a
      further case in a 47-year-old Japanese woman, the product of a consanguineous
      marriage. The remarkable findings in this patient were her normal intelligence,
      Meniere's syndrome, disturbance of peripheral sensory nerves, hearing loss and
      cardiac hypertrophy. alpha-NAGA enzyme activity in her plasma was 0.77% of the
      normal value. Other enzyme activities, such as alpha-galactosidase, beta
      galactosidase, alpha-L-fucosidase, beta-mannosidase and aspartylglucosaminidase,
      were within normal limits. A large quantity of amino acid O-glycans was detected
      in her urine. Gene analysis revealed a novel point mutation (G-->A transition) at
      nucleotide 11018 (986 in the cDNA) resulting in an Arg-329-Gln substitution.
      Kanzaki disease has the same enzyme defect as Schindler disease, but the
      manifestations are quite different.

PMID- 11251575
TI  - Pigmentary anomalies in ataxia--telangiectasia: a clue to diagnosis and an
      example of twin spotting.
AB  - A 6-year-old girl with consanguineous parents presented with a history of
      progressive ataxia and patchy, segmental pigmentary changes, some reminiscent of
      Blaschko's lines. There was no evidence of oculocutaneous telangiectases or signs
      of immunodeficiency. A clinical diagnosis of ataxia--telangiectasia (AT) was
      suggested and confirmed by the presence of a low serum IgA, raised alpha
      fetoprotein and chromosomal rearrangements of chromosomes 7 and 14. This case of
      AT is unique for having hypopigmentation and hyperpigmented patches adjacent to
      each other, which is a feature that has been described as 'cutis tricolor', and
      is unusual for having pigmentary skin changes, some in the lines of Blaschko
      without telangiectases. Clinicians should be aware that a diagnosis of AT may be
      made in the absence of telangiectases.

PMID- 11251576
TI  - Paraneoplastic pemphigus in association with a retroperitoneal Castleman's
      disease presenting with a lichen planus pemphigoides-like eruption. A case report
      and review of literature.
AB  - A 50-year-old man presented with severe mucosal erosions of the lips, oral cavity
      and perianal area, a lichen planus-like eruption on the trunk and extremities and
      scaly plaques of the palms and soles. The clinical impression was of Stevens-
      Johnson syndrome, or paraneoplastic pemphigus (PNP). Histopathology revealed
      vacuolar interface and lichenoid dermatitis with dyskeratosis and suprabasal
      acantholytic vesiculation. Direct immunofluorescence showed deposition of IgG in
      the intercellular space and linear deposition of C3 along the basal membrane
      zone. Indirect immunofluorescence revealed circulating IgG with intercellular
      staining of the epithelium of rat urinary bladder. Western blotting demonstrated
      bands of 250- and 230-kDa antigens. The clinical, histological and immunological
      features were consistent with the lichen planus pemphigoides variant of PNP. A
      retroperitoneal hyaline-vascular Castleman's disease was detected and excised.
      The skin lesions worsened initially after tumour resection but improved
      gradually, leaving extensive melanosis after cyclosporin and mycophenolate
      mofetil treatment.

PMID- 11251577
TI  - Immunoblotting detection of gamma-catenin (plakoglobin) antibody in the serum of
      a patient with paraneoplastic pemphigus.
AB  - We report a patient with paraneoplastic pemphigus associated with a thymic
      tumour. Immunoblot study using affinity-purified gamma-catenin protein revealed
      that his serum recognized gamma-catenin (plakoglobin) in epidermal, thymic tumour
      and mouse bladder extracts.

PMID- 11251578
TI  - Angiosarcoma of the scalp: absence of vascular endothelial cadherin in primary
      and metastatic lesions.
AB  - A 73-year-old man with angiosarcoma of the scalp died about 1 year after disease
      onset, despite systemic and topical administration of recombinant interleukin-2.
      Histopathology showed typical changes of endothelial cells with very sparse
      lymphocytic infiltration into the tumour. An autopsy revealed that the primary
      site penetrated cranial bone and invaded vertically into the subarachnoid space.
      Multiple metastases to lung, chest wall, vertebrae and ribs were also found. On
      immunofluorescence staining, the expression of vascular endothelial cadherin,
      which is present in normal endothelium, was absent from both primary and
      metastatic sites. This may have promoted local invasion and metastasis.

PMID- 11251579
TI  - Human papillomavirus type 58 in Bowen's disease of the elbow.
AB  - Human papillomavirus (HPV) can be detected in skin lesions of Bowen's disease,
      particularly on the fingers, and its genotype is associated with mucosal/genital
      types of HPV. We report herein an 85-year-old woman who had HPV-associated
      Bowen's disease on her elbow. HPV-58 DNA was detected in the lesion by polymerase
      chain reaction with restriction fragment length polymorphism and by Southern blot
      hybridization. In situ hybridization revealed numerous hybrid cells in the nuclei
      of the upper epidermis and stratum corneum of Bowen's disease. A high-risk type
      of mucosal HPV-58 DNA is associated with Bowen's disease in this case, suggesting
      that HPV-related Bowen's disease is not always restricted to genital or finger
      lesions.

PMID- 11251580
TI  - Isolation and polymerase chain reaction typing of Borrelia afzelii from a skin
      lesion in a seronegative patient with generalized ulcerating bullous lichen
      sclerosus et atrophicus.
AB  - A 64-year-old woman presented with bullous and ulcerating lichen sclerosus et
      atrophicus (LSA) on the neck, trunk, genital and perigenital area and the
      extremities. Histology of lesional skin showed the typical manifestations of LSA;
      in one of the biopsies spirochaetes were detected by silver staining. Despite
      treatment with four courses of ceftriaxone with or without methylprednisone for
      up to 20 days, progression of LSA was only stopped for a maximum of 1 year.
      Spirochaetes were isolated from skin cultures obtained from enlarging LSA
      lesions. These spirochaetes were identified as Borrelia afzelii by sodium dodecyl
      sulphate--polyacrylamide gel electrophoresis and polymerase chain reaction (PCR)
      analyses. However, serology for B. burgdorferi sensu lato was repeatedly
      negative. After one further 28-day course of ceftriaxone the lesions stopped
      expanding and sclerosis of the skin was diminished. At this time cultures for
      spirochaetes and PCR of lesional skin for B. afzelii DNA remained negative. These
      findings suggest a pathogenetic role for B. afzelii in the development of LSA and
      a beneficial effect of appropriate antibiotic treatment.

PMID- 11251581
TI  - Pyoderma gangrenosum associated with severe oropharyngeal involvement and IgA
      paraproteinaemia.
AB  - We report a patient with combined cutaneous and oropharyngeal pyoderma
      gangrenosum in association with an IgA lambda paraproteinaemia. The differential
      diagnosis of oral pyoderma gangrenosum is discussed.

PMID- 11251582
TI  - Severe recalcitrant pyoderma gangrenosum responding to a combination of
      mycophenolate mofetil with cyclosporin and complicated by a mononeuritis.
AB  - We describe a 17-year-old boy with severe recalcitrant pyoderma gangrenosum.
      Healing was achieved with a combination of mycophenolate mofetil and cyclosporin,
      negative pressure dressings and split-skin grafts. His recovery was complicated
      by a sciatic nerve palsy, which we believe was caused by direct involvement of
      the nerve at the level of the sciatic notch.

PMID- 11251583
TI  - Novel mutations of TGM1 in a child with congenital ichthyosiform erythroderma.
AB  - We report novel mutations in the transglutaminase (TGase) 1 gene (TGM1) in a
      Japanese boy with non-bullous congenital ichthyosiform erythroderma (NBCIE). The
      patient showed fine, grey or light-brown scales on an erythematous skin. An in
      situ TGase activity assay detected markedly reduced TGase activity in the
      patient's epidermis. Electron microscopy revealed incomplete thickening of the
      cornified cell envelope during keratinization in the epidermis. Sequencing of the
      entire exons and exon-intron borders of TGM1 revealed that the proband was a
      compound heterozygote for two novel mutations, 9008delA and R388H. In lamellar
      ichthyosis, most previously reported TGM1 mutations have been located in the
      central core domain or upstream of the TGase 1 molecule. In the present NBCIE
      patient, the frameshift mutation 9008delA resulting in a premature termination
      codon at the tail of the TGase 1 peptide was in the beta-barrel 2 domain (C
      terminal end domain) of the peptide, far from the active sites of the TGase 1
      molecule, and the mis-sense mutation R388H was in the core domain.

PMID- 11251585
TI  - Familial adult dermatomyositis.

PMID- 11251584
TI  - Alpha 6 beta 4 integrin abnormalities in junctional epidermolysis bullosa with
      pyloric atresia.
AB  - Junctional epidermolysis bullosa with pyloric atresia (JEB-PA) (MIM 226730) is an
      autosomal recessive disorder resulting from mutations in the genes encoding alpha
      6 beta 4 integrin (ITGA6 and ITGB4). Clinically, it is characterized by
      mucocutaneous fragility and gastrointestinal atresia, which most commonly affects
      the pylorus. Additional features of JEB-PA include involvement of the urogenital
      tract, aplasia cutis and failure to thrive. While most affected individuals have
      a poor prognosis resulting in death in infancy, others have milder clinical
      features and a better prognosis. We report two previously undescribed homozygous
      ITGB4 mutations in two unrelated families, which resulted in severe skin
      blistering, pyloric atresia and lethality in infancy. Delineation of the
      mutations was used to undertake DNA-based prenatal diagnosis in subsequent
      pregnancies at risk for recurrence in both families. We review all previously
      published ITGA6 and ITGB4 mutation reports to help define genotype--phenotype
      correlation in this rare genodermatosis.

PMID- 11251586
TI  - Acquired ichthyosis associated with dermatomyositis in a patient with
      hepatocellular carcinoma.

PMID- 11251587
TI  - Squamous cell carcinoma arising in a patient with long-standing pansclerotic
      morphea.

PMID- 11251588
TI  - Genital inflammatory lymphoedema: peculiar microvascular long-distance metastasis
      of gastric carcinoma.

PMID- 11251589
TI  - Drug-induced pemphigus foliaceus with features of pemphigus vulgaris.

PMID- 11251590
TI  - Keratosis lichenoides chronica: characteristics and response to acitretin.

PMID- 11251591
TI  - Multiple cutaneous horns overlying lichen planus hypertrophicus.

PMID- 11251592
TI  - Familial scarring alopecia associated with scalp psoriasis.

PMID- 11251593
TI  - Multigeminate beard hairs and folliculitis.

PMID- 11251594
TI  - Successful treatment regime for folliculitis decalvans despite uncertainty of all
      aetiological factors.

PMID- 11251595
TI  - Nuchal acne keloidalis associated with cyclosporin.

PMID- 11251596
TI  - Phototesting and phototherapy in pityriasis rubra pilaris.

PMID- 11251597
TI  - Dorfman--Chanarin syndrome (neutral lipid storage disease): new clinical
      features.

PMID- 11251598
TI  - A CD4+ CD56+ natural killer-like T-cell systemic lymphoma with haemorrhagic
      cutaneous manifestations.

PMID- 11251599
TI  - Spontaneous regression of cutaneous lesions in adult T-cell leukaemia/lymphoma.

PMID- 11251600
TI  - Generalized eruptive histiocytoma in an infant with healing in summer: long-term
      follow-up.

PMID- 11251601
TI  - Prevalence of solar damage and actinic keratosis in a Merseyside population.

PMID- 11251603
TI  - Digital syringomatous carcinoma mimicking basal cell carcinoma.

PMID- 11251604
TI  - Familial dysmorphophobia.

PMID- 11251605
TI  - Acquired multiple blue naevi scattered over the whole body.

PMID- 11251606
TI  - Erbium:YAG laser ablation of acquired vulval lymphangioma.

PMID- 11251607
TI  - Lupus vulgaris following bacille Calmette-Guerin vaccination.

PMID- 11251608
TI  - Nail diseases in haemodialysis patients: case-control study.

PMID- 11251609
TI  - Polymorphic light eruption treated with cyclosporin.

PMID- 11251610
TI  - The long-term costs of preterm birth and low birth weight: results of a
      systematic review.
AB  - The high rates of morbidity and mortality arising from preterm birth and low
      birth weight impose an immense burden on the health, education and social
      services, and on families. This paper presents the results of a systematic review
      of the published and unpublished evidence regarding the long-term economic
      implications of preterm birth and low birth weight for various sectors of the
      economy and for individuals. The paper highlights the variable methodological
      quality of the bulk of long-term economic studies of preterm birth and low birth
      weight and suggests ways in which these methodological limitations can be
      overcome. The paper reveals that preterm birth and low birth weight can result in
      substantial costs to the health sector following the infant's initial discharge
      from hospital. It can also impose a substantial burden on special education and
      social services, on families and carers of the infants and on society generally.
      In addition to the costs identified by the literature, preterm birth and low
      birth weight can have other long-term consequences that require evaluation from
      an economic perspective.

PMID- 11251611
TI  - The effectiveness of routine health examinations at 2, 6, 9 and 12 months of age:
      experiences based on data from a Swedish county.
AB  - AIM: The aim of this study was to elucidate the role of health surveillance for
      infants during the first year of life in detecting severe health problems. Two
      central questions were addressed: (1) what health problems were detected by
      routine health examinations at the Child Health Centre at the 2-, 6- and 12-month
      check-ups by a physician and at the 9-month check-up by a nurse; and (2) to what
      extent did the health examinations contribute to early identification of children
      with following key abnormalities: congenital heart disease, congenital
      dislocation of the hip, abnormalities as registered at the habilitation centre
      and severe hearing impairments? MATERIAL AND INCLUSION CRITERIA: The study
      population included all children in Uppsala county, born January 1995 to October
      1996, who had participated in at least one of the four health check-ups. There
      were 3107-3487 children in the respective check-ups. METHOD: Data from a county
      health register as well as child health records and information regarding
      referrals were analysed to categorize the health problems by type, severity and
      action taken. Data on children with key abnormalities were obtained from
      specialist units. RESULTS: The rate of suspected new health problems varied
      between 1.9% and 2.8% at the respective check-ups. Of the new problems detected
      by the physician, 21%-36% were false-positive, 34%-44% were minor and 10%-15%
      were moderate. Only two severe health problems were detected among all the
      children during the four check-ups. Of all key abnormalities, 20% were detected
      by way of child health surveillance during the first year of life. IMPLICATIONS:
      Severe health problems and key abnormalities in infants were detected only to a
      limited extent through routine health examinations at 2, 6, 9 and 12 months of
      age. The minor and moderate problems detected justify a health surveillance
      programme, but the organization and content of the programme could be
      reconsidered.

PMID- 11251612
TI  - School peer relationships of 'minority' children in Scotland.
AB  - This paper examines selected issues arising from two studies in mainstream
      education of two minority groupings of children in Scotland-those with serious
      medical conditions and refugee children-completed in 1997 and 1999, respectively.
      It draws on first-person accounts of children, parents and teachers and focuses
      on school-based peer relationships, including friendships. Many of the described
      peer experiences were unhappy or mixed, only a minority were positive. The paper
      relates the research and its findings to current social and educational policy
      contexts and to theories on peer relationships, friendship and rejection. It
      challenges the problematizing of groups or individuals with minority experiences
      and school staff's acceptance of inevitable difficulty in these children's peer
      relationships. It hypothesizes that ways of developing all children's peer
      relationships need to be addressed in schools if the well-being of children who
      may be socially vulnerable is to be improved.

PMID- 11251613
TI  - Bedwetting, behaviour and self-esteem: a review of the literature.
AB  - AIM: The aim of this review was to examine the empirical evidence on the impact
      of bedwetting and its treatment on a child's self-esteem and behaviour. INCLUSION
      CRITERIA: The inclusion criteria for this review were empirical studies conducted
      on children, aged 5-16 years old, with primary nocturnal enuresis using measures
      of self-esteem or behaviour. Studies utilizing psychological measurement scales
      completed by children were the main focus although those that used scales
      completed by parents were also included. SEARCH STRATEGIES: The electronic
      databases from 1981 to 1999 were searched, and hand searching of the literature
      dating back to 1973 was conducted using the reference lists of key papers.
      RESEARCH FINDINGS: Fifteen empirical studies matched the inclusion criteria.
      There was only one randomised-controlled trial and the rest of the studies were
      cohort, case-control or cross-sectional design. Evidence of sample bias
      predominantly due to the use hospital-based and/or 'volunteer' subjects was found
      in five studies. A further five studies used birth cohort data, which excludes
      important variables such as the impact of treatment. Four studies used single
      parent-reported measures, which may under or over-estimate the problem. No large
      cohort studies were available which compare the self-esteem of bedwetting
      children with matched controls. The most interesting line of enquiry is pursued
      by studies looking at whether self-esteem improves with successful treatment.
      However, the use of self-selected subject groups does not make the current
      evidence convincing and more work is required to determine outcomes for all
      children. There is empirical evidence for increased behavioural problems in
      bedwetting children. Studies conducted on younger children report less
      behavioural problems with more reported in studies conducted on older children
      with complex wetting disorders. This may point towards wetting being the primary
      problem, but more work is needed, as causation in any direction is difficult to
      ascertain from the literature.

PMID- 11251614
TI  - Adolescent girls and their babies: achieving optimal birthweight. Gestational
      weight gain and pregnancy outcome in terms of gestation at delivery and infant
      birth weight: a comparison between adolescents under 16 and adult women.
AB  - AIMS: Pregnancy amongst under 16s has been reported to result in worse outcomes
      for the baby, including low birthweight. This study aimed to find out whether the
      under 16s need to gain more weight during pregnancy to avoid this outcome.
      METHOD: A retrospective case control study of pregnancy outcomes in girls
      delivering before the age of 16 and women delivering aged 25-30. Data was
      collected from medical case notes, including maternal age, pregnancy weight gain
      and infant birth weight. RESULTS: Although weight gain amongst under 16s was
      similar to that in the control group, average birthweight of babies born to under
      16s was less than in the older group. For both girls and older women greater
      weight gain in pregnancy did result in higher birth weights. DISCUSSION: As
      younger girls are still growing it may be necessary for them to achieve a greater
      pregnancy weight gain in order to achieve a satisfactory birth weight.

PMID- 11251615
TI  - Co-existence of lysosomal storage diseases in a consanguineous family.
AB  - Lysosomal storage diseases are rare and coexistence of more than one in a family
      can present a diagnostic challenge as illustrated by this study. The index case
      born to consanguineous Asian parents presented with developmental delay.
      Investigations led to an incidental finding of Fabry disease. After numerous
      additional investigations over a year, a second diagnosis of
      aspartylglucosaminuria (AGU) was made. A family history of renal disease and
      developmental delay was disclosed. The sister and first cousin of the index case
      were diagnosed as homozygous for AGU, but do not have Fabry disease. The younger
      brother has since been diagnosed with both Fabry disease and AGU. Another cousin
      has learning difficulties and fits, but is heterozygous for AGU, and possibly has
      another uncharacterised autosomal recessive disorder. In a family with
      consanguinity when the clinical picture in an individual is not fully explained
      by the presence of one rare metabolic disease, it is essential to investigate
      further for the presence of others.

PMID- 11251616
TI  - Attrition among adolescents and infants involved in a parenting intervention.
AB  - Attrition was assessed in a randomized trial of a parenting intervention
      programme for adolescent mothers and their infants. Infants who were admitted to
      the neonatal intensive care unit, mothers who had partner difficulties, and
      mothers and infants who were visited for less than 60 min a week on average
      (typically in the control group) were more likely to miss one of the two follow
      up visits.

PMID- 11251617
TI  - Biological, social, and environmental correlates of preschool development.
AB  - Baseline data from the Canadian National Longitudinal Survey of Children and
      Youth (NLSCY, a population-based study of child health, development and well
      being), were used to determine biological, social and environmental correlates of
      poor development among preschool children. A total weighted sample of 1233 500 (n
      = 6982 unweighted) children aged from birth to 3 years were studied.
      Developmental attainment was measured by the motor, social and development (MSD)
      scale. Children scoring amongst the lowest 15% for their age group were
      categorized as having poor developmental attainment (PDA). Correlates of PDA were
      determined using logistic regression. The MSD scale may not be discriminatory
      enough to identify PDA in children aged < 1 years. Among children aged between 1
      and 3 years, biological factors remain important correlates of PDA, whereas the
      timing of social and environmental factors appears important to their effects on
      developmental attainment. The findings suggest a complex relationship between
      risk factors and developmental outcomes. Correlates of PDA vary according to the
      age of a child. Social and environmental factors appear to play a larger role
      among older children. Prospective studies are required to determine the effect of
      change in risk factor profiles on child development.

PMID- 11251618
TI  - COX-1 sparing drugs in aspirin-sensitive asthma.

PMID- 11251619
TI  - IgE - a marker of late asthmatic response?

PMID- 11251620
TI  - Peptidase allergens, occludin and claudins. Do their interactions facilitate the
      development of hypersensitivity reactions at mucosal surfaces?

PMID- 11251621
TI  - Markers of active airway inflammation and remodelling in chronic obstructive
      pulmonary disease.

PMID- 11251622
TI  - The dendritic cell in allergic airway diseases: a new player to the game.

PMID- 11251623
TI  - Safety of a specific COX-2 inhibitor in aspirin-induced asthma.
AB  - In a subset of patients with asthma, aspirin and several other non-steroidal anti
      inflammatory drugs (NSAID) that inhibit simultaneously cyclooxygenase-1 (COX-1)
      and cyclooxygenase-2 (COX-2) precipitate dangerous asthmatic attacks. We tested
      the hypothesis that in patients with aspirin-induced asthma the attacks are
      triggered by inhibition of COX-1 and not COX-2. In twelve asthmatic patients
      (seven men, five women, average age 39 years) oral aspirin challenge precipitated
      symptoms of bronchial obstruction with fall in FEV1 > 20%, and a rise in urinary
      leukotriene E4 (LTE4) excretion; also in five patients the stable metabolite of
      PGD2, 9alpha11betaPGF2, increased in urine. The patients then entered a double
      blind, placebo-controlled, cross-over study in which they received either placebo
      or rofecoxib in increasing doses 1.5-25.0 mg for 5 consecutive days, separated by
      a 1-week wash-out period. No patient on rofecoxib developed dyspnoea or fall in
      FEV1 > 20%; mean urinary LTE4 and 9alpha11betaPGF2 urinary levels, measured on
      each study day for 6 h post-dosing, remained unchanged. Two patients on placebo
      experienced moderate dyspnoea without alterations in urinary metabolites
      excretion. At least 2 weeks after completion of the study, all patients received
      on an open basis 25 mg rofecoxib without any adverse effects. NSAID that inhibit
      COX-1, but not COX-2, trigger asthmatic attacks in patients with asthma and
      aspirin intolerance. Rofecoxib can be administered to patients with aspirin
      induced asthma.

PMID- 11251624
TI  - Interaction of cigarette smoke and house dust mite allergens on inflammatory
      mediator release from primary cultures of human bronchial epithelial cells.
AB  - Several studies have shown that exposure to cigarette smoke and/or house dust
      mite (HDM) can lead to increased airway inflammation in susceptible individuals.
      The underlying mechanisms, however, are not defined. To investigate the
      interaction between cigarette smoke and HDM allergen on mediator release from
      primary cultures of human bronchial epithelial cells. Confluent human bronchial
      epithelial cell cultures were exposed to cigarette smoke in the absence or
      presence of HDM allergen and investigated for the release of IL-8, IL-1beta, and
      sICAM-1. Damage to the epithelial cells themselves was assessed by release of
      51Cr. On separate occasions, we investigated the effect of PTL11028, a highly
      potent and selective Der p1 inhibitor, on HDM allergen-induced release of IL-8,
      following activation of HDM allergen by incubation with cysteine. The effect of
      cigarette smoke exposure on the stability of these released mediators in prepared
      solutions in the absence/presence of reduced glutathione was also studied. Both
      HDM allergens and short-term (20 min) cigarette smoke exposure led to a
      significantly increased release of IL-8, IL-1beta and sICAM-1 from the epithelial
      cell cultures. Longer exposure (1-6 h) to cigarette smoke led to a dramatic
      decrease in the amount of these mediators detected in the culture medium. Whilst
      incubation of epithelial cultures with HDM allergen did not cause any significant
      change in the release of 51Cr from pre-loaded cells, cigarette smoke on its own
      led to a marked, exposure and incubation-time dependent increase in the release
      of 51Cr. Incubation with HDM allergen led to a significant, dose and time
      dependent increase in the release of IL-8, which was further enhanced when the
      allergen extract was pre-activated with cysteine. This effect was completely
      abrogated by PTL11028, a novel Der p1 inhibitor. Prepared solutions of various
      concentrations of IL-8, IL-1beta and sICAM-1 exposed to cigarette smoke
      demonstrated a dramatic exposure time-dependent decrease in the detectable amount
      of these mediators, an effect which was abrogated by GSH. HDM-induced airway
      inflammation may include Der p-mediated release of inflammatory mediators from
      epithelial cells. Additionally, short-term cigarette smoke exposure may induce
      airway inflammation by release of inflammatory mediators from these cells, an
      effect which may be potentiated by Der p allergens. Longer term cigarette smoke
      exposure may cause damage to epithelial cells and changes in the structure of
      inflammatory mediators.

PMID- 11251625
TI  - Antigen-specific IgE and IgA antibodies in bronchoalveolar lavage fluid are
      associated with stronger antigen-induced late phase reactions.
AB  - The mechanism(s) leading to the development of late phase allergic reactions is
      (are) unknown. Previous studies have indicated that a relationship between serum
      IgE and the late phase exists. To explore the relationships between allergen
      specific immunoglobulins in bronchoalveolar lavage (BAL) fluids and the magnitude
      of airflow limitation during the late phase response to inhaled allergen. Ragweed
      specific IgE, IgA, secretory IgA (sIgA) and IgG were measured in BAL fluid and in
      the serum 1-5 weeks before whole lung antigen challenge with ragweed extract, in
      16 ragweed allergic asthmatics. In addition, BAL and serum eosinophil cationic
      protein (ECP) and BAL fibrinogen levels were determined and BAL cells counted and
      differentiated. The latter procedures were repeated in a second BAL performed 24
      h after the end of the ragweed challenge. After the challenge, lung function was
      monitored hourly for 8 h, to record the magnitude of airflow limitation. Ragweed
      specific immunoglobulins were detected in 25% to 37.5% of BAL samples. Compared
      to the subjects with undetectable BAL fluid ragweed-specific IgE levels at
      baseline, those with detectable antibodies had stronger late phase reactions as
      determined by the nadir of FEV1 between hours 4 and 8 after the ragweed
      inhalation challenge (P = 0.0007). Allergen-induced changes in BAL ECP and
      fibrinogen levels were also higher in those subjects with detectable ragweed
      specific IgE in baseline fluids (P = 0.03 and P = 0.005, respectively).
      Significant relationships between BAL antigen-specific IgA, serum ragweed
      specific IgE and IgA and the late phase reaction were also found. The results of
      this study point towards the possibility that allergen-specific IgE and IgA may
      be independently involved in the pathogenesis of the late phase reaction. This
      notion merits further exploration.

PMID- 11251626
TI  - Interleukin-2 inhibits eosinophil migration but is counteracted by IL-5 priming.
AB  - Conflicting data on the role of interleukin-2 in the recruitment of eosinophil
      granulocytes (EOS) to sites of inflammation have been presented. The objective of
      the present study was to investigate the effect of recombinant human IL-2 and
      anti-IL-2 on the migration of purified blood EOS. Neutralizing antibodies to IL-2
      were added to a cytokine mixture with significant eosinophil chemotactic activity
      (ECA), and afterwards the ECA was tested on EOS from both normal and allergic
      donors. EOS migration was measured by a modification of the Boyden technique,
      using a 48-well microchemotaxis chamber. Recombinant human IL-2 was either added
      to the lower compartment of the chemotaxis chamber, or to the EOS for a pre
      incubation period of 20 min, before migration assays towards the chemotaxins were
      performed. Anti-IL-2 caused a significant increase of EOS migration towards the
      cytokine mixture. Pre-incubation of the EOS with rhIL-2 inhibited the chemotaxis
      towards RANTES, PAF, IL-8 and eotaxin, and EOS migration towards IL-2 was lower
      than that towards buffer. These effects were more pronounced on EOS from normal
      than from allergic donors. Priming of the EOS with IL-5 prevented the inhibitory
      effect of IL-2. We hypothesize that IL-2 acts as an autocrine regulator of EOS
      migration, and that this inhibitory effect may be downregulated in allergy,
      allowing an increased migration of EOS towards chemotactic factors.

PMID- 11251627
TI  - Dietary factors associated with physician-diagnosed asthma and allergic rhinitis
      in teenagers: analyses of the first Nutrition and Health Survey in Taiwan.
AB  - The occurrence of asthma and allergy are related to lifestyle factors, and
      dietary pattern may be one of the contributing factors. To examine the possible
      association between dietary intake and the prevalence of asthma and allergic
      rhinitis in teenagers. In a population-based cross-sectional survey, the
      relationship was sought between food frequency and physician-diagnosed asthma and
      allergic rhinitis in 1166 adolescents aged 13-17. The prevalence was 4.0% for
      asthma and 12.4% for rhinitis. Living in an urbanized area was a significant
      predictor of asthma and rhinitis. In univariate analysis, higher frequencies of
      oily fish, butcher's meat, liver and deep-fried foods were associated with
      asthma. Relevant food frequency variables were dichotomized at the 75th
      percentile for multivariate logistic regression analysis, which included
      adjustment for two levels of urbanization. Asthma was associated with intakes of
      liver (OR = 2.32, 95%CI 1.11-4.80), deep-fried foods (OR = 2.13, 95%CI 1.06-4.30)
      and butcher's meat (OR 1.84, 95%CI 0.89-3.80). In a similar analysis, allergic
      rhinitis was associated with liver (OR = 1.67, 95%CI 1.06-2.63). No protective
      effect was demonstrated for any of the food items examined. Protein-rich and fat
      rich foods of animal origin were associated with a higher prevalence of asthma in
      teenagers.

PMID- 11251628
TI  - Increased leukotriene production by food additives in patients with atopic
      dermatitis and proven food intolerance.
AB  - Recently, we identified a subgroup of patients with atopic dermatitis (AD) with a
      clinical relevant food intolerance proven by double blind placebo controlled
      challenge. In search of possible pathomechanisms involved in this food
      intolerance, which leads to aggravation of the disease, the aim of the present
      study was to determine sulfidoleukotriene production in these patients using
      isolated leucocytes from the peripheral blood after stimulation with different
      food additives. Leukotriene production of peripheral leucocytes was detected by
      incubation of isolated cells with the food additives at different concentrations
      ranging from 0.2 to 200 microg/mL after pre-stimulation with IL-3. Ten non-atopic
      donors (A), nine AD patients of the diet responder group with negative oral
      provocation test against food additives (B) and nine patients of the responder
      group with positive reactions after the oral provocation test (C) were
      investigated. In the non-atopic group (A), no increased sulfidoleukotriene (sLT)
      release was observed for all food additives tested. In group B, increased sLT
      production was determined using tartrazine in one patient (1/9) and using nitrite
      in two patients (2/9), whereas sLT production remained below the cut-off range in
      all patients of group B (9/9) using benzoate, metabisulfite and salicylate. By
      contrast, in group C increased sLT production was observed with food colour mix
      in 1/9, with tartrazine in 3/9, with benzoate in 4/9, with nitrite in 5/9, with
      salicylate in 2/9 and with metabisulfite in 1/9. However, no increased sLT
      concentration was determined in the presence of the tested food additives in two
      patients of group C. Increased sLT production by peripheral leucocytes in the
      presence of single food additives was observed in the majority of patients with a
      proven food intolerance towards food additives proven by double-blind-placebo
      controlled challenges. These food additives were particulary tartrazine, benzoate
      and nitrite. These findings indicate that single food additives as aggravating
      factors in AD patients may trigger the disease through increased sLT production
      as a pathophysiological mechanism.

PMID- 11251629
TI  - The NK-2 receptor antagonist SR 48968C does not improve adenosine
      hyperresponsiveness and airway obstruction in allergic asthma.
AB  - When stimulated, excitatory nonadrenergic noncholinergic (e-NANC) nerves locally
      release tachykinins like Neurokinin (NK) A and Substance P, causing neurogenic
      inflammation and airway obstruction via activation of specific NK-1 and NK-2
      receptors. The recently developed nonpeptide NK-2 receptor antagonist SR 48968C
      has a high affinity for the NK-2 receptor, and is a strong and selective
      antagonist of NK-2 receptor mediated airway obstruction. In a placebo-controlled
      cross-over study, we investigated the effect of SR 48968C, administrated orally
      once-daily in a dosage of 100 mg during 9 days, on airway responsiveness to
      adenosine 5'-monophosphate (AMP) in 12 allergic asthmatic patients. Furthermore,
      we assessed its effect on airway obstruction, by measuring FEV1 on the first and
      last day of each treatment period and by peak flow registration at home
      throughout the study period. SR 48968C had no significant effect on PC20AMP or on
      FEV1 measured on day 1 and 9, and morning and evening peakflow measured at home
      on day 2-8. Thus, although SR 48968C was administrated in a dosage that might
      cause a demonstrable blocking effect on airway NK-2 receptors in asthma, it did
      not have a significant bronchodilatory or bronchoprotective effect against
      adenosine hyperresponsiveness in this study. Further studies are needed to assess
      the value of SR 48968C and other NK receptor antagonists in the treatment of
      asthma

PMID- 11251630
TI  - The transmembrane protein occludin of epithelial tight junctions is a functional
      target for serine peptidases from faecal pellets of Dermatophagoides
      pteronyssinus.
AB  - There have been only a few studies of how allergens cross the airway epithelium
      to cause allergic sensitization. House dust mite fecal pellets (HDMFP) contain
      several proteolytic enzymes. Group 1 allergens are cysteine peptidases, whilst
      those of groups 3, 6 and 9 have catalytic sites indicative of enzymes that
      mechanistically behave as serine peptidases. We have previously shown that the
      group 1 allergen Der p 1 leads to cleavage of tight junctions (TJs), allowing
      allergen delivery to antigen presenting cells. In this study we determined
      whether HDMFP serine peptidases similarly compromise the airway epithelium by
      attacking TJs, desmosomes and adherens junctions. Experiments were performed in
      monolayers of MDCK, Calu-3 or 16HBE14o-epithelial cells. Cell junction morphology
      was examined by 2-photon molecular excitation microscopy and digital image
      analysis. Barrier function was measured as mannitol permeability. Cleavage of
      cell adhesion proteins was studied by immunoblotting and mass spectrometry. HDMFP
      serine peptidases led to a progressive cleavage of TJs and increased epithelial
      permeability. Desmosomal puncta became more concentrated. Cleavage of TJs
      involved proteolysis of the TJ proteins, occludin and ZO-1. This was associated
      with activation of intracellular proteolysis of ZO-1. In contrast to occludin, E
      cadherin of adherens junctions was cleaved less extensively. Although Calu-3 and
      16HBE14o-cells expressed tethered ligand receptors for serine peptidases, these
      were not responsible for transducing the changes in TJs. HDMFP serine peptidases
      cause cleavage of TJs. This study identifies a second general class of HDM
      peptidase capable of increasing epithelial permeability and thereby creating
      conditions that would favour transepithelial delivery of allergens.

PMID- 11251632
TI  - Identification of some rabbit allergens as lipocalins.
AB  - Rabbits are frequently used as laboratory animals or kept as domestic pets.
      Rabbit serum albumin and a 17-kDa protein referred to as Ory c 1 have previously
      been reported as allergens. Several other allergenic proteins have been
      recognized by crossed immuno-electrophoresis but have not been characterized. The
      aim of this study was to characterize the allergenic proteins present in rabbit
      saliva, urine and fur on the basis of molecular size and, where possible, to
      determine their amino acid sequences. Extracts from the male New Zealand white
      rabbit were used for developing specific direct RAST and RAST inhibition assays.
      Proteins in the extracts were separated by SDS-PAGE and the individual allergens
      identified by immunoblotting with serum from rabbit-allergic individuals. The N
      termini of four allergens were sequenced. Saliva was the most potent extract. In
      total, 26 protein bands were recognized as allergens in the three extracts: 12 in
      saliva, seven in urine and seven in fur. Their molecular weights ranged from an 8
      kDa species in saliva to an 80-kDa protein in urine. The N terminal sequences of
      an 18 kDa and a 21-kDa species in saliva, were identified as lipocalins with
      sequence similarity to a recently described odourant binding protein. This is the
      first evidence that allergens from the rabbit are members of the lipocalin
      superfamily of proteins, suggesting that similar mechanisms may be involved in
      eliciting the allergic response to rabbits. The 18 kDa allergen from saliva may
      be the previously named rabbit allergen, Ory c 1.

PMID- 11251631
TI  - Identification of vacuolar serine proteinase as a major allergen of Aspergillus
      fumigatus by immunoblotting and N-terminal amino acid sequence analysis.
AB  - Aspergillus species are common airborne fungi that have been identified as
      causative agents of extrinsic bronchial asthma. More than 10 allergens from A.
      fumigatus have been recently characterized by cDNA cloning. The objective of this
      study is to identify A. fumigatus allergens through immunoblot analysis using
      sera from asthmatic patients. IgE-binding components of A. fumigatus and IgE
      cross-reactivity among allergens of different prevalent airborne fungal species
      were analysed by immunoblot and immunoblot inhibition, respectively, using sera
      from asthmatic patients. The N-terminal amino acid sequences of major allergens
      identified were determined by Edman degradation. Among two batches (70 and 41
      sera) of asthmatic sera tested, 19 (27%) and 14 (34%), respectively, have IgE
      immunoblot reactivity towards components of A. fumigatus. A 34-kDa protein that
      reacts with IgE antibodies in 15 (79%) and 11 (79%) of the 19 and 14 positive
      samples, respectively, may be considered a major allergen of A. fumigatus. The N
      terminal amino acid sequences of the 34 kDa major allergen and the 30.5 and 30
      kDa IgE-binding components of A. fumigatus showed sequence identity to that of
      the vacuolar serine proteinase from A. fumigatus. The results from immunoblot
      inhibition show IgE cross-reactivity among major allergens of A. fumigatus, P.
      notatum and P. oxalicum. Results obtained suggest that the 34 kDa major allergen
      of A. fumigatus may be a vacuolar serine proteinase. There is IgE cross
      reactivity among serine proteinase allergens of A. fumigatus, P. notatum and P.
      oxalicum.

PMID- 11251633
TI  - Immunological and molecular characterization of the major allergens from lilac
      and privet pollens overproduced in Pichia pastoris.
AB  - The main allergens from privet and lilac pollens, Lig v 1 and Syr v 1, are
      proteins homologous to Ole e 1 and have been shown to be involved in cross
      reactivity. To overproduce the correctly folded Lig v 1 and Syr v 1 allergens and
      to study their immunological properties in comparison with those of their natural
      counterparts. The yeast Pichia pastoris was used as an expression system to
      produce these recombinant allergens. The proteins were isolated by ion-exchange
      and size-exclusion chromatographies. Amino acid quantifying, Edman degradation,
      mass spectrometry and circular dichroism were carried out to obtain molecular
      properties of the recombinant proteins. Anti-Ole e 1 monoclonal and polyclonal
      antibodies, as well as sera from patients allergic to olive pollen, were used in
      immunoblotting and ELISA for immunological characterization. Recombinant Lig v 1
      and Syr v 1 were secreted at high yield to the extracellular medium of the yeast.
      The purified proteins displayed the native conformation, as deduced from their
      spectroscopic properties and binding ability to an IgG monoclonal antibody. The
      recombinant allergens behaved similarly to their natural counterparts when they
      were analysed against Ole e 1-specific antibodies. IgE and IgG binding properties
      of lilac and privet allergens to olive allergic sera and Ole e 1-specific
      antibodies indicated that these molecules share common B-cell epitopes with Ole e
      1. P. pastoris yeast is an appropriate system for the efficient production of Ole
      e 1-like allergens, which could be used as analogous allergens and predictors of
      clinical sensitization.

PMID- 11251634
TI  - Purification and characterization of the main allergen of Plantago lanceolata
      pollen, Pla l 1.
AB  - English plantain (Plantago lanceolata) pollen is an important cause of pollinosis
      in the temperate regions of North America, Australia and Europe. However, very
      little is known about its allergen composition. The aim of this study was to
      identify plantain allergens, and to isolate and characterize a major allergen.
      Allergens were identified by immunoblotting with individual allergic patients'
      sera. Isolation of the major allergen was achieved by sequential reverse-phase
      and size-exclusion HPLC. Allergenic characterization was performed by ELISA and
      immunoblotting after SDS-PAGE with sera from plantain-allergic patients. N
      terminal amino acid sequence was established by Edman degradation. Allergograms
      showed that 13 out of the 14 sera assayed had IgE to a group of proteins with a
      molecular weight in the range of 16-20 kd, that turned out to be different
      isoforms or variants of the major allergen Pla l l. Eighteen amino acid residues
      from the N-terminal end of one of the isoforms, and 10 of three others, were
      sequenced, and a partial sequence identity with Ole e 1 was found. Prevalence of
      specific IgE to purified Pla l 1 in plantain allergic patients was 86%, and
      represents about 80% of the total IgE-binding capacity of the plantain extract.
      The most relevant allergen from P.lanceolata pollen, Pla l 1, has been purified
      and characterized. This contributes to a greater knowledge of the allergen
      composition of this important weed, and clears the way for the standardization of
      plantain allergen products in terms of major allergen content.

PMID- 11251635
TI  - Discontinuous IgE-binding epitopes contain multiple continuous epitope regions:
      results of an epitope mapping on recombinant Hol l 5, a major allergen from
      velvet grass pollen.
AB  - The knowledge of IgE-binding epitopes on allergen molecules is important for
      better understanding allergen-antibody interactions and, thus, for developing new
      strategies for immunotherapy. Our purpose was to more precisely define the number
      and structure of IgE-binding epitopes of a paradigmatic major grass pollen
      allergen. We performed an IgE-binding epitope mapping of rHol l 5, a group V
      pollen allergen of velvet grass (Holcus lanatus), with overlapping fragments
      (length between 15 and 186 amino acids), which were expressed in E. coli as MBP
      fusion proteins. Using sera of 65 grass pollen allergic patients, the fragments
      were analysed by immunoblotting for IgE reactivity. Specificity of antibody
      binding was confirmed by competitive blot inhibition assays. At least four
      different continuous IgE-binding epitopes were identified on small fragments
      (about 30 amino acids), and at least five different discontinuous IgE-binding
      epitopes on larger fragments, which were destroyed by further fragmentation. The
      fragments were differentially recognized by individual patients' sera. By
      investigating IgE-binding to one of the small fragments in more detail, we found
      further epitope regions on this fragment. It was noteworthy that IgE reactivity
      to small fragments was weak compared to large fragments or to the complete
      molecule. Competitive blot inhibition experiments showed that binding of IgE
      antibodies to the small fragments was specific but with lower avidity than to the
      complete rHol l 5. rHol l 5 harbours multiple discontinuous as well as continuous
      IgE-binding epitopes spread over the whole molecule, which were individually
      recognized by IgE antibodies from different patients. Low avidity of IgE
      antibodies to small fragments suggests that the continuous epitope regions do not
      represent the complete epitope and are most probably parts of discontinuous
      epitopes.

PMID- 11251636
TI  - Central nervous system regeneration: mission impossible?
AB  - 1. Attempts to induce clinical repair after central nervous system injury, such
      as spinal cord damage, are likely to involve several protocols because eliciting
      a regenerative response from an injured central neuron is a complex task. Future
      treatments, applied when a window of opportunity exists, address the requirements
      for regeneration. 2. Application of trophic support to the lesion site for
      axotomized neurons aims to initiate and maintain a cell body response conducive
      to axonal regrowth. 3. Surgical intervention may provide a bridge across the
      injury site that contains either Schwann cells or olfactory bulb ensheathing
      cells derived from the patient's own tissue. 4. The application of antibodies may
      block the inhibitory action of myelin-associated molecules and other glial
      elements. 5. Gene therapy may induce the correct cascade of guidance molecules to
      be released at appropriate times. 6. Physical rehabilitation may ensure that
      muscle wastage is reduced and encourages functional reconnection.

PMID- 11251637
TI  - Two possible mechanisms underlying nitrate tolerance in monkey coronary arteries.
AB  - 1. Previous studies using isolated arteries have demonstrated cross-tolerance
      between nitric oxide (NO) donors such as nitroglycerin (NTG) and sodium
      nitroprusside (SNP). However, it remains unclear whether the vasorelaxing effect
      of atrial natriuretic peptide (ANP), an activator of particulate guanylate
      cyclase, is affected by treatment with NO donors. To investigate the cross
      tolerance and interactions between NTG and ANP in coronary vasorelaxant
      responses, we used two models of monkey coronary arterial strips (Macaca
      fuscata). 2. In one model, which was induced by a 1 h treatment with 4.4 x 10(-4)
      mol/L NTG followed by washout of the agent for 1 h, the vasorelaxing effects of
      subsequent NTG were markedly attenuated, whereas those of ANP and NO were not
      affected. These findings suggest that the development of NTG tolerance is
      associated with a biotransformation process from NTG to NO. In the other model,
      which did not include washout after exposure to 3 x 10(-6) mol/L NTG, the
      vasorelaxant responses to 10(-8) mol/L ANP (31.1+/-5.4 vs 5.1+/-2.1%,
      respectively; P < 0.001), 10(-6) mol/L NO (61.5+/-2.4 vs 29.5+/-8.5%,
      respectively; P < 0.001) and 10(-8) mol/L SNP (49.4+/-6.4 vs 8.0+/-2.0%,
      respectively; P < 0.001) were significantly attenuated. The concentration-
      response curve for 8-bromo-cGMP (8-Br-cGMP) was shifted to the right, whereas
      responses to papaverine and forskolin were unchanged. These findings suggest that
      an intracellular process that occurs after the synthesis of cGMP is responsible
      for this interaction. 3. As a mechanism of NTG tolerance, two possible processes
      may be impaired: (i) biotransformation from NTG to NO; and (ii) an intracellular
      process that occurs after the synthesis of cGMP.

PMID- 11251638
TI  - Chronic administration of docosahexaenoic acid improves the performance of radial
      arm maze task in aged rats.
AB  - 1. In the present study, we investigated the effect of docosahexaenoic acid (DHA)
      on spatial memory related learning ability in aged (100 weeks) male Wistar rats.
      2. Rats were fed a fish oil-deficient diet through three generations and were
      then randomly divided into two groups. Over 10 weeks, one group was per orally
      administered 300 mg/kg per day DHA dissolved in 5% gum Arabic solution and the
      other group was administered the vehicle alone. Five weeks after the start of the
      administration, rats were tested with the partially baited eight-arm radial maze
      to estimate two types of spatial memory related learning ability displayed by
      reference memory error and working memory error. 3. Chronic administration of DHA
      significantly decreased the number of reference memory errors and working memory
      errors. 4. The level of lipid peroxide (LPO) in the hippocampus tended to
      decrease with chronic DHA administration and demonstrated a positive correlation
      with the number of reference memory errors. 5. These results suggest that the
      accumulation of hippocampal LPO reduces spatial memory related learning ability
      in aged rats. Moreover, chronic administration of DHA was effective in decreasing
      the level of hippocampal LPO, then improving learning ability.

PMID- 11251639
TI  - beta-Adrenoceptor blocking activities of nipradilol and its optical isomers in
      pig coronary artery.
AB  - 1. beta-Adrenoceptor blocking activities of nipradilol, its four optical isomers
      (RR, RS, SR, SS) and denitro nipradilol were evaluated using pig isolated
      coronary arteries. 2. (-)-Isoprenaline produced concentration-dependent
      relaxations of the arteries, which were antagonized by nipradilol, its four
      optical isomers or denitro nipradilol under KCl-induced contracture. 3. The order
      of pA2 values for beta-adrenoceptor blocking activities was SR > nipradilol > SS
      > or = denitro nipradilol > RR > RS. 4. The nitroxy group in nipradilol appears
      to enhance its beta-adrenoceptor blocking activity, because the beta-adrenoceptor
      blocking activity of nipradilol was more potent than that of denitro nipradilol.
      5. Isomers that have the S configuration (SR, SS) at the 2' position (having a
      hydroxyl group) in the aryloxypropanolamine showed more potent beta-adrenoceptor
      blocking activity than isomers that have the R configuration (RR, RS). 6. Isomers
      that have the R configuration (SR, RR) at the 3 position (having a nitroxy group)
      in the benzopyran ring showed more potent beta-adrenoceptor blocking activity
      than those with the S configuration (SS, RS). 7. It is suggested that the
      difference in configuration of the chemical structure of nipradilol may result in
      variations of binding affinity for the beta-adrenoceptor.

PMID- 11251640
TI  - Pharmacology of a unique adenosine binding site in rat brain using a selective
      ligand.
AB  - 1. In order to further characterize the adenosine binding sites that we
      previously purified and termed P3 purinergic receptor-like protein (P3LP), a
      reliable binding assay method was developed using [3H]-5'-N
      ethylcarboxamidoadenosine (NECA) as a radioligand and the newly developed high
      affinity selective ligand 9-(6,7-dideoxy-beta-D-allo-hept-5-ynofuranosyl) adenine
      (HAK2701) as a selective displacer. 2. Using this assay method, it was found that
      rat brain membranes possess high- and low-affinity [3H]-NECA binding sites. The
      high-affinity binding site showed KD and Bmax values of 19.7+/-2.5 nmol/L and
      0.192+/-0.05 pmol/mg protein, respectively, and the KD value for the low-affinity
      binding site was 4260+/-330 nmol/L. The KD value for the high-affinity site
      agreed well with that of the [3H]-NECA binding site determined with the partially
      purified P3LP preparation described previously. 3. The distribution of P3LP in
      rat tissues was determined using the [3H]-NECA binding method described above.
      The highest level of P3LP was in the cerebellum followed by the olfactory bulb
      and the spinal cord. 4. The order of the affinity for various purinergic or
      related compounds to P3LP in rat brain preparations was also determined by the
      [3H]-NECA binding method to be HAK2701 > NECA = adenosine 5'-O-(2
      thiodiphosphate) > cAMP = beta,gamma-methyleneadenosine 5'-triphosphate >
      diadenosine tetraphosphate > alpha,beta-methyleneadenosine 5'-triphosphate > 5'
      deoxy-5'-methylthioadenosine > N6-cyclopentyladenosine. 5. These studies reveal
      that the [3H]-NECA binding assay in combination with HAK2701 is successful in the
      characterization of P3LP, especially the membrane-bound form.

PMID- 11251641
TI  - Changes in endogenous monoamines in aged rats.
AB  - 1. It has been documented that ageing may alter endogenous neurotransmitters.
      However, these results are controversial. Thus, in the present study, cerebral
      cortex and plasma from male Wistar rats aged 8 weeks and 6, 12 or 24 months were
      used to investigate the changes in monoamines using electrochemical detection. 2.
      A marked decrease in L-dihydroxyphenylalanine (L-DOPA) was observed in aged rats.
      Like the decrease in dopamine (DA), levels of 5-hydroxytryptamine (5-HT) and 5
      hydroxyindolacetic acid (5-HIAA), the major metabolite of 5-HT, in aged rats were
      decreased in the cerebral cortex and plasma. Plasma levels of noradrenaline and
      levels of adrenaline in the cerebral cortex were also decreased in aged rats.
      Moreover, levels of 3,4-dihydroxyphenylacetic acid (DOPAC), a metabolite of DA,
      in the cerebral cortex and plasma were reduced by ageing. The level of
      homovanillic acid (HVA) in all samples was markedly increased with ageing. 3. The
      ratio of DOPAC/DA and 5-HIAA/5-HT, being closely linked with the activity of
      monoamine oxidase, was increased in the cerebral cortex and plasma with ageing.
      The ratio of HVA/DOPAC, an index of the activity of catechol-O-methyltransferase,
      was also higher in the cerebral cortex and plasma of aged rats. 4. These data
      suggest that ageing may alter endogenous monoamines in both the brain and
      peripheral tissues.

PMID- 11251642
TI  - Type IV phosphodiesterase inhibitor suppresses insulin-dependent myocardial
      glucose uptake.
AB  - 1. Phosphodiesterase (PDE) IV has been localized at cardiomyocytes and the
      coronary vasculature and modulates cAMP, but the effect of PDE IV on myocardial
      glucose uptake has not been demonstrated. 2. Glucose uptake in rat isolated
      hearts treated with the PDE IV inhibitor rolipram was measured by [31P] nuclear
      magnetic resonance spectroscopy. 3. Under non-stimulating conditions, glucose
      uptake was not significantly different between control and rolipram (1
      micromol/L)-treated rat hearts, whereas enhanced uptake in insulin-stimulated
      conditions was significantly attenuated by rolipram. 4. Phosphodiesterase IV
      inhibitor negatively affects insulin-dependent myocardial glucose uptake.

PMID- 11251643
TI  - Structure-specific membrane-fluidizing effect of propofol.
AB  - 1. While recent studies about the pharmacological mechanism of the intravenous
      anaesthetic propofol (2,6-diisopropylphenol) have focused on its interaction with
      functional proteins, there is the possibility that propofol alters membrane
      properties to produce anaesthesia. In the present study, the structure-specific
      effects of propofol on liposomal model membranes were studied. 2. The effect of
      propofol on the phase transition of membrane phospholipid was analysed
      spectrophotometrically using 1,2-dipalmitoyl-L-alpha-phosphatidylcholine
      liposomes. Propofol (50-200 micromol/L) lowered the phase transition temperature
      to fluidize membranes. 3. Membrane fluidization was also analysed by measuring
      fluorescence polarization of liposomes consisting of 1,2- dipalmitoyl-L-alpha
      phosphatidylcholine, 1-palmitoyl-2-oleoyl-L- alpha-phosphatidylcholine and
      cholesterol with different probes. Propofol fluidized all liposomal membranes in
      the concentration range 5-500 micromol/L by acting on both the inner and outer
      layers of the membranes. 4. The membrane effects of propofol were compared with
      those of 2,6-dialkylphenols, 1,3-dialkylbenzenes, 2-alkylphenols and
      alkylbenzenes. Although the membrane-fluidizing effects were shared by a series
      of structural analogues, propofol was most effective in fluidizing membranes,
      especially liposomal membranes consisting of 20 mol% cholesterol and 80 mol% 1
      palmitoyl-2-oleoyl-L-alpha-phosphatidylcholine. 5. Lipophilicity was compared
      between propofol and its structural analogues using their capacity factors,
      determined by reverse-phase high-performance liquid chromatography. The potency
      of propofol to fluidize membranes was much greater than anticipated from its
      lipophilicity. 6. At 0.125-1.0 micromol/L, almost corresponding to clinically
      relevant concentrations, propofol significantly enhanced membrane fluidity of
      cholesterol-containing 1-palmitoyl-2-oleoyl-L-alpha-phosphatidylcholine
      liposomes. 7. These results indicate that propofol fluidizes membranes in a
      structure-specific manner through an interaction with membrane lipids. Such a
      membrane effect may be responsible for the mode of anaesthetic action of
      propofol.

PMID- 11251644
TI  - Hyperglycaemia: a morphine-like effect produced by naloxone.
AB  - 1. Naloxone, which is often regarded as a pure opioid antagonist, produces
      effects similar to those produced by morphine. 2. In conscious rabbits implanted
      with an intracerebroventricular (i.c.v.) cannula, naloxone, whether given
      intravenously (1 mg/kg) or i.c.v. (1-100 microg), produced a significant rise in
      blood glucose levels. 3. Hyperglycaemia in response to naloxone (1 mg/kg, i.v.,
      or 100 microg, i.c.v.) was not influenced by the selective alpha1-adrenoceptor
      antagonist WB-4101 given either i.v. (50 microg) or i.c.v. (5 microg). 4.
      Hyperglycaemia in response to naloxone (1 mg/kg, i.v., or 100 microg, i.c.v.) was
      completely blocked by pretreatment with the alpha2-adrenoceptor antagonist
      yohimbine (1 mg/kg, i.v., or 100 microg, i.c.v.). However, hyperglycaemia to
      i.c.v. naloxone (100 microg) was not influenced by i.v. yohimbine (1 mg/kg). 5.
      Because naloxone behaves like morphine and produces hyperglycaemia in conscious
      rabbits, the drug may have an appreciable agonist activity and the hyperglycaemic
      response to naloxone is principally mediated via alpha2- but not alpha1
      adrenoceptors.

PMID- 11251645
TI  - The peripheral renin-angiotensin system is not involved in the hypertension of
      sheep exposed to prenatal dexamethasone.
AB  - 1. Fetal exposure to an adverse intrauterine environment has been linked with
      cardiovascular and metabolic disease later in life. We have shown previously, in
      sheep, that brief exposure (48 h) to maternally administered dexamethasone (0.28
      mg/kg per day) at 27 days of gestation (prenatal treatment group (PTG) 1; term
      approximately 150 days), but not at 64 days of gestation (PTG2), produced
      hypertensive offspring at 40 months of age. The present study aimed to determine
      whether the elevated blood pressure in these sheep was associated with an altered
      peripheral renin-angiotensin system (RAS). 2. Measurements of the basal levels of
      the RAS components (renin, angiotensinogen, angiotensin (Ang) I, angiotensin-
      converting enzyme (ACE), AngII and Ang-(1-7)) were made. In addition, we studied
      the effect of a peripherally administered AngII type 1 (AT1) receptor antagonist
      (irbesartan at 1.02 mg/kg per h) on mean arterial pressure (MAP) over 4.5 h. 3.
      There was no significant difference in basal plasma concentrations of the
      components of the RAS measured between control (n = 7) and PTG1 (n = 5) or PTG2
      (n = 6) animals. The MAP in PTG1 was significantly higher than in the control
      group during both vehicle infusion and AT1 receptor blockade. The effect of 4.5 h
      irbesartan (1.02 mg/kg per h) infusion on blood pressure was similar between the
      groups. 4. In conclusion, intrauterine exposure for 48 h to maternally
      administered dexamethasone at 27 days of gestation caused elevated blood pressure
      in adult sheep that does not appear to be associated with an alteration in the
      peripheral RAS.

PMID- 11251646
TI  - Effect of 9-(6,7-dideoxy-beta-D-allo-hept-5-ynofuranosyl)adenine on noradrenaline
      release from vascular sympathetic nerves.
AB  - 1. The effects of 9-(6,7-dideoxy-beta-D-allo-hept-5-ynofuranosyl)adenine
      (HAK2701), a selective and potent ligand for P3 receptor-like protein, on the
      release of endogenous noradrenaline (NA) from electrically stimulated rat
      mesenteric artery and rabbit ear artery were compared with those of a number of
      purinoceptor agonists. 2. In the rat mesenteric artery, the P1 receptor agonists
      2-chloroadenosine (2CA) and 5'-N-ethylcarboxamidoadenosine (NECA) and the P2
      purinoceptor agonists beta,gamma-methylene ATP (betagammamATP) and 2-methylthio
      ATP (2mSATP) significantly inhibited the release of NA in a xanthine-sensitive
      manner. HAK2701 did not significantly inhibit the release of NA, the relative
      order of potency being betagammamATP > NECA > 2CA > 2mSATP >> HAK2701. 3. In the
      rabbit ear artery, both P1 and P2 receptor agonists significantly facilitated the
      release of NA in a xanthine-sensitive manner. HAK2701 also significantly
      facilitated the release of NA, the relative order of potency being HAK2701 >
      betagammamATP > 2CA > 2mSATP > NECA. 4. These findings suggest that HAK2701 may
      be a potent and selective agonist for facilitatory prejunctional purinoceptors,
      but not for inhibitory purinoceptors, on adrenergic nerve terminals.

PMID- 11251647
TI  - The lung is the major site that produces nitric oxide to induce acute pulmonary
      oedema in endotoxin shock.
AB  - 1. The present study was undertaken to determine the locus of nitric oxide (NO)
      production that is toxic to the lung and produces acute pulmonary oedema in
      endotoxin shock, to examine and compare the effects of changes in lung perfusate
      on endotoxin-induced pulmonary oedema (EPE) and to evaluate the involvement of
      constitutive and inducible NO synthase (cNOS and iNOS, respectively). 2.
      Experiments were designed to induce septic shock in anaesthetized rats with the
      administration of Escherichia coli lipopolysaccharide (LPS). Exhaled NO, lung
      weight (LW)/bodyweight (BW) ratio, LW gain (LWG) and lung histology were measured
      and observed to determine the degree of EPE 4 h following LPS. The EPE was
      compared between groups in which LPS had been injected either into the systemic
      circulation or into the isolated perfused lung. The lung perfusate was altered
      from whole blood to physiological saline solution (PSS) with 6% albumin to test
      whether different lung perfusions affected EPE. Pretreatment with various NOS
      inhibitors was undertaken 10 min before LPS to investigate the contribution of
      cNOS and iNOS to the observed effects. 3. Endotoxin caused profound systemic
      hypotension, but little change in pulmonary arterial pressure. The extent of EPE
      was not different between that induced by systemic injection and that following
      administration to isolated lungs preparations. Replacement of whole blood with
      PSS greatly attenuated (P < 0.05) EPE. In blood-perfused lungs, pretreatment with
      NOS inhibitors, such as Nomega-nitro-L-arginine methyl ester, aminoguanidine and
      dexamethasone, significantly prevented EPE (P < 0.05). 4. The major site of NO
      production through the whole blood is in the lung. The NO production mediated by
      the iNOS system is toxic to the endothelium in the pulmonary microvasculature.
      Inhalation of NO for patients with sepsis may be used with clinical caution.
      Therapeutic consideration of lung extracorporeal perfusion with PSS and
      pharmacological pretreatment with iNOS inhibitors may be warranted.

PMID- 11251648
TI  - Gene expression studies using microarrays.
AB  - 1. The rapid progression of the collaborative sequencing programmes that are
      unravelling the complete genome sequences of many organisms are opening pathways
      for new approaches to gene analysis. As the sequence data become available, the
      bottleneck in biological research will shift to understanding the role of each of
      these genes. Techniques that enable the analysis of large sets of genes in one
      experiment will elucidate the interactions of genes in diverse biological
      systems. 2. Microarrays, which consist of large numbers of cDNA or
      oligonucleotides spotted onto a glass microscope slide, are one such technology.
      RNA isolated from two populations of cells, one control and one altered by
      experimental treatment or disease, is labelled with two different fluorochromes
      before being hybridized to the microarray. After a standard hybridization
      reaction, a scanner records the intensity of the two fluorochromes. The data can
      be analysed using special software that enables clustering of genes that have
      similar expression patterns. 3. Such powerful analysis techniques will provide
      information about genes whose functions are currently unknown and enhance our
      understanding of how genes interact to provide molecular control. This increase
      in knowledge about gene function will allow new targeted approaches for the
      development of drugs and/or gene therapies.

PMID- 11251651
TI  - Coagulation tests in differential diagnosis.
AB  - Bleeding disorders pose a special problem for the practising physician
      haematologist or laboratory coagulation specialist. Great concern is placed on
      specimen integrity, either during handling or in storage. Heparin contamination,
      activated specimens and factor VIII lability are common issues.

PMID- 11251649
TI  - Allosteric modulation of the GABA(A) receptor in rat hypothalamus by somatostatin
      is altered by stress.
AB  - 1. This autoradiographic study was conducted to investigate somatostatin
      modulation of GABA(A) receptor binding in hypothalamic structures of
      immobilization-stressed rats. 2. GABA(A) receptor binding was labelled with [35S]
      t- butylbicyclophosphorothionate (TBPS), which binds in or near the chloride
      channel. 3. Several structures of the rat hypothalamus (i.e. the peri- and
      paraventricular nuclei) display an increase in [35S]-TBPS binding as well as an
      alteration of the modulatory effect of somatostatin on the GABA(A) receptor
      complex under stress. Furthermore, these results demonstrate for the first time
      that somatostatin is particularly effective in modifying [35S]-TBPS binding to
      the GABA(A) receptor in rat hypothalamus.

PMID- 11251652
TI  - Clinical approach to the patient with unexpected bleeding.
AB  - Bleeding can be considered unexpected if it is disproportionate to the intensity
      of the haemostatic stress in a patient with no known haemorrhagic disorder or if
      it occurs in a patient in whom a bleeding disorder has been characterized but is
      adequately treated. A thorough history usually allows the clinician to predict
      reasonably accurately whether the patient is likely to have a systemic
      haemostatic defect (and if so whether it is congenital or acquired), or whether
      the bleeding likely has a purely anatomical basis. The nature of bleeding is
      instructive with respect to preliminary categorization. Thus, mucocutaneous
      bleeding suggests defects of primary haemostasis (disordered platelet-vascular
      interactions). Bleeding into deeper structures is more suggestive of coagulation
      defects leading to impaired fibrin clot formation, and delayed bleeding after
      primary haemostasis is characteristic of hyperfibrinolysis. Localized bleeding
      suggests an anatomical cause, although an underlying haemostatic defect may
      coexist. Where bleeding is so acutely threatening as to require urgent
      intervention, diagnosis and treatment must proceed simultaneously. In the case of
      minor haemorrhage (not threatening to life or limb) it may be preferable to defer
      therapy while the nature of the bleeding disorder is methodically investigated.
      Initial laboratory evaluation is guided by the preliminary clinical impression.
      The amount of blood loss can be inferred from the haematocrit or haemoglobin
      concentration, and the platelet count will quickly identify cases in which
      thrombocytopenia is the likely cause of bleeding. In the latter instance,
      examination of the red cell morphology, leucocyte differential, and mean platelet
      volume may allow the aetiological mechanism to be presumptively identified as
      hypoproliferative or consumptive. With regard to coagulation testing, the
      activated PTT, prothrombin time, and thrombin time usually constitute an adequate
      battery of screening tests, unless the clinical picture is sufficiently
      distinctive to indicate the immediate need for more focused testing. In any
      event, sufficient blood should be taken to allow more detailed studies to be done
      based on the results of these screening tests. These results will direct the need
      for further assays, such as specific clotting factor activity levels, von
      Willebrand factor assays, tests for coagulation inhibitors, platelet function
      assays, and markers of primary or secondary fibrinolytic activity.

PMID- 11251653
TI  - Obstetrical and gynaecological bleeding: a common presenting symptom.
AB  - Excessive haemorrhage is one of the commonest symptom when women present to
      obstetricians and gynaecologists. In the majority of cases the cause is related
      to the primary obstetric and gynaecological pathology and is easily identified.
      However, less commonly, the bleeding is unexpected and due to an undiagnosed
      underlying coagulation defect, the commonest of which is von Willebrand (vWD)
      disease. Menorrhagia is a common, and may be the only, clinical manifestation of
      an inherited bleeding disorder. Screening 150 women with menorrhagia, vWD was
      diagnosed in 13% of patients and other hereditary haemorrhagic disorders in
      another 4%. Menorrhagia with onset at the menarche was predictive of an inherited
      bleeding disorder in 65% of vWD and 67% of FXI deficient patients. Therefore,
      testing for bleeding disorders should be considered in women with menorrhagia
      especially those with early onset and no obvious pelvic pathology. Childbirth and
      puerperium present a special risk for excessive haemorrhage. The risk of
      postpartum haemorrhage is very high in women with inherited bleeding disorders.
      In our centre, the incidence of primary and secondary postpartum haemorrhage was
      22% and 11% in carriers of haemophilia 18.5% and 20% in vWD and 16% and 24% in
      FXI deficient women, respectively. Acquired haemophilia can be an unusual cause
      of severe and unexpected postpartum haemorrhage with a very high mortality rate.
      Unexplained postpartum and postoperative haemorrhage that does not respond to
      general measures should alert clinicians to the possibility of bleeding disorders
      as a causative factor. In addition, increased awareness among obstetricians and
      gynaecologists of these less common causes and close collaboration with the local
      haemophilia centre and availability of management guidelines are essential for
      optimal outcome.

PMID- 11251654
TI  - Surreptitious bleeding in surgery: a major challenge in coagulation.
AB  - Apart from inadequate surgical haemostasis, postoperative bleeding can be related
      to acquired disorders of platelet number, platelet function or coagulation
      proteins (e.g. Vitamin K deficiency, DIC or liver injury). We highlight our
      experience with three patients who suffered life-threatening bleeding in the
      postoperative setting. The three patients - a 47-year-old man and 70- and 74-year
      old women -- all had negative histories for excessive bleeding with prior
      surgeries, and all had normal preoperative PT and aPTT tests. Surgeries were
      resection of ischaemic bowel, cholecystectomy and coronary artery bypass
      grafting. All patients experienced unexpected bleeding within the first few
      postoperative days requiring multiple red cell transfusions and surgical re
      explorations. Evaluations within the first 4--7 days after surgery revealed that
      these three patients had developed prolonged aPTT due to demonstrable factor VIII
      antibodies initially at low titre. One patient was treated with high doses human
      factor VIII, corticosteroids, intravenous gammaglobulin and plasma exchanges. The
      inhibitor was no longer demonstrable after 6 weeks of such therapy, and he has
      remained in remission without therapy. The second patient was initially treated
      with high-dose human factor VIII infusions. Five months later, prednisone and 6
      mercaptopurine were begun for worsening inhibitor titre and diffuse purpura and
      subcutaneous haematomas. The factor inhibitor remitted, but the patient died from
      liver failure related to post-transfusion hepatitis. The third patient was
      initially managed with high-dose human factor VIII. Two months later, worsening
      inhibitor titre and tongue haematoma was treated with activated prothrombin
      complex, corticosteroids and cyclophosphamide. Eight years later, she is on no
      therapy, demonstrates a mild bleeding tendency and has a stable low-titre
      inhibitor. There have been a few case reports of inhibitors to coagulation
      factors including factor VIII becoming manifest in the postoperative setting but
      surgery has not been widely recognized as an underlying cause for acquired
      haemophilia. This paper speculates on pathogenesis and reviews treatment options.
      This syndrome is remarkable for its abrupt onset in the first few postoperative
      days and for its substantial morbidity. The problem is potentially reversible
      with immunosuppressive therapy. Clinicians should be aware of this syndrome,
      considering acquired haemophilia in patients with unexpected postoperative
      bleeding.

PMID- 11251655
TI  - Spontaneous inhibitors to coagulation factors.
AB  - Spontaneous inhibitors to coagulation factors are autoantibodies that usually
      appear in the elderly, but may also occur in patients with immunological
      disorders such as lupus, lymphoma, asthma or drug reactions. Most antibodies are
      directed against factor VIII, but any coagulation protein may be affected. They
      should be suspected in individuals who previously had normal haemostasis, but who
      now begin to experience bleeding into the skin and muscles, or suffer
      haemorrhages after routine procedures such as insertion of vascular catheters,
      intramuscular injections, or minor surgery. The haemostasis laboratory is
      critical in identifying the particular inhibitor and quantitating its potency.
      Factor VIII inhibitors prolong the partial thromboplastin time (PTT) but not the
      prothrombin time (PT), and incubating mixtures of patient plasma and normal
      plasma enhances the prolongation of the clotting time. The Bethesda assay
      provides a rough assessment of inhibitor potency. Inhibitors of von Willebrand
      factor prolong the bleeding time and impair ristocetin-induced platelet
      aggregation. Factor V inhibitors are associated with a prolonged PTT and PT, not
      correctable with normal plasma. Patients will often have a history of exposure to
      bovine thrombin in fibrin glue. The antibodies most difficult to recognize are
      those that alter fibrin polymerization or stabilization. Abnormal clot retraction
      or clot solubility in urea solutions are an important clue. The management of
      these disorders depends on characterization of the inhibitor, and using
      appropriate clotting factor concentrates to control acute bleeding. For example,
      recombinant human factor VIII or desmopressin may be effective for patients with
      low titre factor VIII inhibitors, whereas porcine factor VIII, recombinant factor
      Vlla, or prothrombin complex concentrates stem bleeding in those with high
      titres. Inhibitors of von Willebrand factor may be amenable to desmopressin,
      cryoprecipitate, or von Willebrand factor concentrates. Some patients with factor
      V inhibitors have responded to platelet transfusions, as the platelet factor V
      may be shielded from the autoantibody. Bleeding due to factor XIII inhibitors may
      be managed with fibrogammin, a factor XIII concentrate. All patients should be
      treated for underlying disorders and given drugs such as corticosteroids and
      cytotoxic agents to suppress inhibitor formation. Major advances in new
      immunosuppressive technologies, such as monoclonal B-cell antibodies, offer hope
      of more effective therapies for spontaneous inhibitors to coagulation factors.

PMID- 11251656
TI  - Unexpected bleeding disorders: Algorithm for approach to therapy.
AB  - The management of unexpected bleeding must be directed at the specific
      abnormality identified, as there is no universally effective and safe
      procoagulant product. Where practical, a purely pharmaceutical approach obviates
      the residual risks of exposure to plasma-derived products. Desmopressin is often
      effective in bleeding due to mild haemophilia A, Type I von Willebrand's disease
      and some platelet function disorders. Where replacement therapy is necessary, it
      should be as specific as possible, preferably using purified components singly or
      in combination. Recombinant proteins provide the greatest margin of safety, but
      it must be borne in mind that these are biologicals, and that they may contain
      human and animal plasma-derived proteins. Where specific replacement is
      unavailable or impractical, plasma or crudely fractionated plasma derivatives may
      be used. In the case of inhibitor antibodies to factor VIII, high dose human
      factor VIII or porcine factor VIII may be used. Where replacement therapy is
      impossible due to a high inhibitory titre, it may be necessary to bypass the
      specific haemostatic defect using activated prothrombin complex concentrates or
      recombinant activated factor VIIa. The latter product is being studied in
      patients with various disorders of platelet function, and in the more global
      haemostatic failure that accompanies end-stage liver disease. Ancillary methods
      are often of great value in securing haemostasis. These may be derived from
      pharmacological or biological sources, and their sites of action may be systemic
      or topical. Examples include antifibrinolytic lysine analogues, corticosteroids
      where inflammation accompanies bleeding, and the topical application of fibrin
      sealants or thrombin. Simple physical measures such as pressure, ice, or
      splinting are also valuable adjunctive measures. Finally, it must be emphasized
      that the ultimate control of bleeding often depends upon effective management of
      the inciting cause, such as eliminating the trigger for DIC, or suppressing the
      causative antibody of ITP. These principles will be presented using a practical
      algorithmic approach. The initial question when considering treatment should be
      whether or not the patient is acutely unstable. Instability may be due to one of
      two causes: the volume of blood loss leading to a compromised cardio-vascular
      status, or the site of the bleed. The relevance of the site of the bleed is
      independent of the volume of blood loss, so for example, a closed bleed into CNS
      will cause critical functional compromise even though the volume of bleeding may
      be minimal. Similarly bleeding into a compartment, such as into a forearm or a
      calf will cause critical functional compromise irrespective of the volume of
      bleeding.

PMID- 11251657
TI  - Microbial analysis of bone collected during implant surgery: a clinical and
      laboratory study.
AB  - Dental implant surgery produces bone debris which can be used to correct bone
      defects in the "simultaneous-augmentation" technique. However, this debris is
      potentially contaminated with oral bacteria. Therefore, this study examined bone
      debris collected during dental implant surgery in order 1) to identify the
      microbial contaminants and 2) to compare the effects of two different aspiration
      protocols on the levels of microbial contamination. Twenty-four partially dentate
      patients were randomly allocated into two equal groups and underwent bone
      collection using the Frios Bone Collector during surgery to insert two endosseous
      dental implants. In group S (using a stringent aspiration protocol), bone
      collection occurred within the surgical site only. In group NS (utilizing a non
      stringent aspiration protocol), bone collection and tissue fluid control was
      achieved using the same suction tip. Bone samples were immediately transported
      for microbial analysis. Colonial and microscopic morphology, gaseous requirements
      and identification kits were utilized for identification of the isolated
      microbes. Twenty-eight species were identified including a number associated with
      disease, in particular, Enterococcus faecalis and Staphylococcus epidermidis as
      well as the anaerobes Actinomyces odontolyticus, Eubacterium sp., Prevotella
      intermedia, Propionibacterium propionicum and Peptostreptococcus
      asaccharolyticus. In group S (stringent aspiration protocol), significantly fewer
      organisms were found than in group NS, the non-stringent aspiration protocol
      (P=0.001). Gram-positive cocci dominated the isolates from both groups. It is
      concluded that if bone debris is collected for implantation around dental
      implants, it should be collected with a stringent aspiration protocol (within the
      surgical site only) to minimize bacterial contaminants.

PMID- 11251658
TI  - Lethal photosensitization for decontamination of implant surfaces in the
      treatment of peri-implantitis.
AB  - Peri-implantitis is considered to be a multifactorial process involving bacterial
      contamination of the implant surface. A previous study demonstrated that a
      combination of toluidine blue O (100 microgram/ml) and irradiation with a diode
      soft laser with a wavelength of 905 nm results in an elimination of Porphyromonas
      gingivalis (P. gingivalis), Prevotella intermedia (P. intermedia), and
      Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans) on different
      implant surfaces (machined, plasma-flame-sprayed, etched, hydroxyapatite-coated).
      The aim of this study was to examine the laser effect in vivo. In 15 patients
      with IMZ implants who showed clinical and radiographic signs of peri-implantitis,
      toluidine blue O was applied to the implant surface for 1 min and the surface was
      then irradiated with a diode soft laser with a wavelength of 690 nm for 60 s.
      Bacterial samples were taken before and after application of the dye and after
      lasing. The cultures were evaluated semiquantitatively for A.
      actinomycetemcomitans, P. gingivalis, and P. intermedia. It was found that the
      combined treatment reduced the bacterial counts by 2 log steps on average. The
      application of TBO and laser resulted in a significant reduction (P<0.0001) of
      the initial values in all 3 groups of bacteria. Complete elimination of bacteria
      was not achieved.

PMID- 11251659
TI  - Bisphosphonate inhibits alveolar bone resorption in experimentally-induced peri
      implantitis in dogs.
AB  - The purpose of this study was to determine the effect of bisphosphonate on
      alveolar bone resorption in experimentally-induced peri-implantitis in beagle
      dogs. Experimental peri-implantitis was induced by ligation around the abutments,
      6 months after placement of a fixture. Pamidronate (0.6 mg/kg) was injected
      intramuscularly every 3 days into each of 5 dogs. Another 5 dogs served as the
      control group and were injected with saline only. Peripheral blood and urine
      samples were collected every week up to 12 weeks after placement of the ligature.
      Standard X-rays were taken every week. Urinary deoxypyridinoline (DPD) and serum
      osteocalcin (OC) were evaluated by ELISA as markers of alveolar bone remodeling.
      X-ray films were analyzed with a computer image analyzer. After 12 weeks, the
      bone level was measured after removal of the gingival flap. The distance between
      the top surface of the fixture and the fundus of the defect was significantly
      lower in the Pamidronate group (1.59+/-0.55 mm, mean+/-SD) than in the control
      group (2.41+/-0.48 mm). Bone density analyzed from the X-ray films was
      significantly higher in the bisphosphonate group (69.2+/-8.7%, mean+/-SD) than in
      the control group (50.3+/-12.8%) after 2 to 8 weeks compared with the baseline
      value (100%). OC and DPD levels fluctuated during the experimental period. These
      findings suggest that bisphosphonate inhibits the progression of alveolar bone
      resorption during ligature-induced peri-implantitis in dogs.

PMID- 11251660
TI  - Absorbable versus nonabsorbable membranes and bone grafts in the treatment of
      ligature-induced peri-implantitis defects in dogs. Part I. A clinical
      investigation.
AB  - The purpose of this study was to clinically evaluate an absorbable collagen
      membrane (Bio-Gide) and a nonabsorbable polytetrafluoroethylene membrane (PTFE),
      associated or not with bone grafts, for the treatment of ligature-induced peri
      implantitis defects in dogs. The bilateral mandibular premolars were removed from
      5 2-year-old mongrel dogs. After 3 months of healing, 3 titanium implants were
      placed on each side of the mandible. Experimental peri-implantitis was induced
      after abutment connection. Ligatures and abutments were removed after 1 month and
      the bone defects were randomly assigned to one of the following treatments: DB:
      debridement alone; GBR+BG-I: debridement plus PTFE membrane associated with
      mineralized bone graft (Bio-Oss); GBR+BG-II: debridement plus collagen membrane
      (Bio-Gide) associated with mineralized bone graft; GBR-I: debridement plus PTFE
      membrane; GBR-II: debridement plus collagen membrane; BG: debridement plus
      mineralized bone graft. The peri-implant bone defects were measured before and 5
      months after treatment. Results showed the greatest percentage of vertical bone
      fill for GBR+BG-II (27.77+/-14.07) followed by GBR-II (21.78+/-16.19), BG
      (21.26+/-6.87), GBR+BG-I (19.57+/-13.36), GBR-I (18.86+/-10.63) and DB (14.03+/
      5.6). However, the values were not statistically significant (ANOVA, contrast F
      test, P=0.612). Within the limits of the present investigation, it can be
      concluded that no difference was detected among treatments.

PMID- 11251661
TI  - Temporal and local appearance of alkaline phosphatase activity in early stages of
      guided bone regeneration. A descriptive histochemical study in humans.
AB  - Alkaline phosphatase (ALP) catalyzes the hydrolysis of phosphate esters and it
      seems to be a prerequisite for normal skeletal mineralization. Also, ALP is the
      most widely recognized marker of osteoblast phenotypes. By a tissue regenerative
      technique called Guided Bone Regeneration (GBR), it is possible nowadays to
      regenerate small bony defects. The aim of the present study was to investigate
      early events in bone healing and neogenesis by studying histochemically the
      temporal and local appearance of the marker Alkaline Phosphatase (ALP) in a GBR
      model system. Nine healthy volunteers (5 males, 4 females, mean age 31.7 years)
      participated in the experiment. After raising a mucoperiosteal flap from the
      mandibular second molar to the retromolar area in each volunteer, a hollow
      titanium test cylinder was placed into a congruent bony bed and the coronal end
      of the cylinder was closed with an ePTFE-membrane. Then the flap was adapted and
      sutured to obtain primary wound closure. After 2, 7 and 12 weeks, the regenerated
      tissue within the cylinders was harvested. Histologically, ALP activity was
      observed associated with the osteoid seams in the very basal part of the
      regenerate where new bone trabeculae were in the process of being formed. More
      coronally, large round cells seemed to secrete an ALP-positive substance since in
      the center of such cell clusters strong ALP activity located extracellularly was
      detected. In the present experiment, ALP seemed to have been an early sign of
      osteoblast secretion of a matrix which subsequently was determined to become
      osteoid. ALP activity was never seen isolated within connective tissue and away
      from bone. This is an indication that its source is linked to existing bone. The
      present study has documented for the first time the appearance of ALP activity in
      guided bone regenerations in humans. It has revealed that: 1) Osteogenesis in
      guided bone regeneration is preceded by localized, marked expression of ALP in an
      organized connective tissue environment. 2) Bone neogenesis is an early event in
      this experimental setup and may be detected already 2 weeks after wounding. 3)
      Expression of ALP and subsequent bone neogenesis is originating from and
      topographically linked to pre-existing bone structures.

PMID- 11251662
TI  - Histologic evaluation of the bone integration of TiO(2) blasted and turned
      titanium microimplants in humans.
AB  - Twenty-seven patients received 2 microimplants each during implant surgery. One
      microimplant was blasted with 25 microm sized particles of TiO(2); the other was
      left as machined i.e. a turned surface. Before insertion the surface topography
      was characterized with an optical confocal laser profilometer. The surface
      roughness was greater than standard implants, and was similar for both surface
      modifications averaging over all parts of the implant i.e. tops, valley and
      flanks. The mean surface roughness from flank measurements only replicated
      previously reported findings: i.e. significantly rougher surfaces on blasted
      implants. After a mean healing period of 6.3 months in the maxillae and 3.9
      months in the mandible, the microimplants and surrounding tissue were removed
      with a trephine burr. The histomorphometrical evaluation demonstrated
      significantly higher bone-to-implant contact for the blasted implants, inserted
      in the maxilla or in the mandible. Significantly more bone was found inside the
      threaded area for the blasted implants in the mandible, but there was no
      difference for implants positioned in maxillae.

PMID- 11251663
TI  - A clinical histologic study of bovine hydroxyapatite in combination with
      autogenous bone and fibrin glue for maxillary sinus floor augmentation. Results
      after 6 to 8 months of healing.
AB  - Biopsies were taken from 16 out of 20 consecutive referral patients 6 to 8 months
      after maxillary sinus floor augmentation with a mixture of bovine hydroxyapatite
      (BH), autogenous bone particles and fibrin glue. Four days prior to biopsy
      retrieval the patients were given a single dose of tetracycline to label bone
      forming sites. Fluorescence microscopy of 100 microm thick sections revealed
      active bone formation in conjunction with the BH particles in 14 of 15 specimens
      analysed. Light microscopy and morphometry of ground sections from 16 patients
      showed various amounts of mineralised bone tissue in all except one specimen. In
      the latter case, the BH particles were encapsulated by a dense fibrous connective
      tissue. Sections from the augmented areas were occupied by non-mineralized tissue
      (54.1+12.6%), lamellar bone (21.2+24.5%), BH particles (14.5+10.3%) and woven
      bone (10.2+13.4%). The non-mineralized tissue seen in bone forming areas
      consisted of a loose connective tissue, rich of vessels and cells, and in the
      periphery of a more dense fibrous connective tissue. Woven bone with large and
      scattered osteocyte lacunae was bridging between the BH particles and the
      lamellar trabecular bone. There were no signs of resorption of the BH particles.
      The lamellar bone appeared to have originated from the recipient site and was
      seldom in contact with the BH particles. It is concluded that the tested implant
      material has bone conducting properties. The bone associated with the BH
      particles after 6 to 8 months of healing was mainly woven.

PMID- 11251664
TI  - Biological reactions of alveolar bone to orthodontic loading of oral implants.
AB  - Enosseous oral implants have been suggested as anchorage for orthodontic
      appliances in cases where the existing dentition cannot provide sufficient
      stability. Long-term studies of oral implants have suggested that excessive
      loading may contribute as an etiologic factor in the pathogenesis of failing
      implants. The purpose of the present study was to perform a histomorphometric
      analysis of tissue reactions around implants subjected to a well-defined force
      system. The analysis was performed on undecalcified sections cut perpendicularly
      to the long axis of the implant. The degree of osseointegration, bone density at
      varying distances from the implant as well as the relative extent of resorption
      and formation of alveolar bone adjacent to the implant-bone interface were
      evaluated. The results were correlated with the local strain of the tissue
      estimated by the means of a finite element analysis. It was found that loading
      significantly influenced both the turnover and the density of the alveolar bone
      in the proximity of the implants. However, even unloaded implants tended to
      maintain the bone characteristics of the alveolar process. On the other hand, the
      degree of osseointegration appeared to be independent of the loading of the
      implant.

PMID- 11251665
TI  - Reproducibility of peri-implant probing using a force-controlled probe.
AB  - The aim of the present study was to evaluate the reproducibility of probing depth
      (PD) and vertical attachment level (PAL-V) measurements at endosseous implants.
      Twenty partially edentulous patients who had received 44 Frialit-2 and 30 Astra
      implants between 1994 and 1996 were examined. At all teeth and implants, clinical
      parameters (GI, PlI, PD, PAL-V) were measured at 6 sites using the flexible
      plastic version of the universal explorer TPS probe. At the implants and at teeth
      that were in similar locations compared to the implants, PD and PAL-V
      measurements were repeated. For each of the 20 probes that had been used for
      clinical examination of the 20 patients, the probing force was assessed using a
      precision balance. As a measure of intraexaminer reproducibility, the following
      standard deviations of single PD and PAL-V measurements were calculated: Frialit
      2: 0.71/0.74 mm; Astra: 0.72/0.75 mm; tooth: 0.59/0.57 mm (PD/PAL-V). Stepwise
      multiple regression analysis revealed implant/tooth position and GI to influence
      PD and PAL-V measurement error (P<0.001). At anterior teeth, a lower variability
      was observed than at posterior teeth (P<0.001). PD and PAL-V measurement error
      were higher at implants than at teeth and influenced by patients. The respective
      models explained 13% and 17% of the variability of the dependent variable (PD/PAL
      V), respectively. Intraexaminer variability of PD and PAL-V measurements at
      implants tended to be higher than at teeth. Multivariate analysis of variance
      revealed probe and probe holder to statistically significantly (P<0.001)
      influence probing force. However, the differences in probing force between the
      various probe heads were very small. They reached a maximum of 0.054 N between
      probe 3 and 14 and may be looked upon as clinically irrelevant.

PMID- 11251666
TI  - A comparison of hydroxylapatite coated implant retained fixed and removable
      mandibular prostheses over 4 to 6 years.
AB  - In a 6-year prospective clinical study, 181 hydroxylapatite coated endosseous
      dental implants were placed into the anterior mandible of 48 patients. Twenty-one
      patients were treated with fixed prostheses and 27 patients with an overdenture.
      When the implants were exposed all 181 had integrated. To date, there is 100%
      survival of all implants and they all retain a functioning prostheses. The
      initial results were very promising, in both groups the interval success was over
      95% in the first 4 years of the study. However, by year 6, the interval success
      rates had fallen to 83% for both the fixed and removable groups. This study also
      compares the construction and maintenance complications for the two types of
      restorations. The clinical time taken, after implant exposure, to construct the
      prostheses was similar whether the fixed (mean of 8 visits) or removable option
      (mean of 7 visits) was chosen. However, the removable restoration cost less than
      half the price of the fixed when both technical time and implant component costs
      were evaluated. Maintenance for both groups was higher than expected, but
      patients required more appointments in the removable group both in the first year
      and beyond. Regarding the prostheses itself, the incidence of remakes, relines
      and general adjustments was higher in the removable group. This study has shown
      that the overdenture offers an effective and initially a more economical
      alternative to the fixed prostheses, in the treatment of the edentulous mandible.
      However, long-term maintenance of such a prosthesis can be significant.

PMID- 11251667
TI  - Evaluation of speech in patients rehabilitated with various oral implant
      supported prostheses.
AB  - In the present study, speech function was assessed in edentulous patients wearing
      fixed or removable dental prostheses supported or not by oral implants. A total
      of 138 patients participated in the present research. The experimental group
      (n=113) was divided in 4 subgroups. Subgroup FD/FFPi comprised 22 patients with a
      maxillary full denture (=FD) and a mandibular fixed full prosthesis on implants
      (=FFPi). Subgroup FFPi/ND consisted of 27 patients with a maxillary fixed full
      prosthesis on implants and a natural dentition (=ND) in the mandible. Subgroup
      FD/ODi included 49 patients wearing a maxillary full denture and a mandibular
      overdenture on 2 implants (=ODi). Subgroup FFPi/FFPi comprised 15 patients having
      a fixed full prosthesis on implants in both jaws. The outcome of the logopedic
      screening of the experimental group was compared with that of a control group of
      subjects having a natural dentition (ND/ND; n=25). A standard clinical procedure
      for evaluation of speech was carried out by a speech pathologist. Besides,
      specific oral and prosthetic parameters were scored in all patients. It was
      established that one or more pronunciation difficulties occurred in 84% of the
      patients of the experimental group. This was significantly more than in the
      control group, where half the number of subjects had some speech deficiencies. No
      clear influence of specific oral and prosthetic parameters could be identified.
      From the present results, it could be concluded that in patients rehabilitated
      with oral implant-supported prostheses speech disorder is more frequently
      observed than in subjects with a natural dentition.

PMID- 11251668
TI  - Glass fiber-reinforced abutments for dental implants. A pilot study.
AB  - Titanium abutments in dental implants shine through all-ceramic crowns and
      therefore limit excellent esthetic results. Prototypes of tooth-colored fiber
      reinforced abutments were investigated to avoid the shining-through effect. In
      vitro, the fracture strength was determined after thermal cycling and mechanical
      loading of all-ceramic single crowns and four-unit bridges made of a fiber
      reinforced composite. The suprastructures were adhesively fixed onto fiber
      reinforced implant abutments and compared with those fixed on standard titanium
      abutments. The median of the fracture strength of the titanium-supported all
      ceramic crowns was significantly higher than the median of crowns fixed onto the
      prototypes. But this value was still more than twice as high as the maximum
      loading force under oral conditions. No statistical difference was found between
      four-unit bridges made by fiber-reinforced composite inserted onto titanium
      abutments and those inserted onto fiber-reinforced abutments. Fiber-reinforced
      abutment prototypes for dental implants avoided the shining-through effect
      associated with metal abutments. Their load-bearing capacity after in vitro
      stress simulation was higher than the maximum oral loading force. With some
      improvements, the fiber-reinforced implant abutments are therefore a promising
      alternative to titanium abutments.

PMID- 11251669
TI  - Inter-abutment and peri-abutment mucosal enlargement with mandibular implant
      overdentures.
AB  - A variety of terms have been used to describe changes in the oral mucosa around
      abutments underneath fixed and removable implant prostheses such as mucosal
      inflammation, peri-implant mucosal hyperplasia, gingival hyperplasia,
      hyperplastic tissue, mucosal proliferation, proliferative gingivitis and peri
      implant mucositis. Although such terms have become part of the evidence-based
      literature, there is no histological evidence to support the descriptive
      terminology used by authors. The use of the alternative term mucosal enlargement
      for clinical observations underneath mandibular implant overdentures is proposed.
      Prospective and retrospective reports have failed to use similar criteria to
      measure periodontal parameters in relation to these mucosal changes, both in
      keratinized or non-keratinized tissues. Therapeutic remedies for mucosal
      enlargement are dictated by authors' opinions on the possible aetiology. This
      literature review, coupled with clinical observations during a 5-year prospective
      study, prompts this proposal of the term mucosal enlargement underneath splinted
      and unsplinted mandibular implant overdentures.

PMID- 11251670
TI  - Islet transplantation.

PMID- 11251671
TI  - Human islet cell transplantation--future prospects.
AB  - BACKGROUND: Islet transplantation has the potential to cure diabetes mellitus.
      Nevertheless despite successful reversal of diabetes in many small animal models,
      the clinical situation has been far more challenging. The aim of this review is
      to discuss why insulin-independence after islet allotransplantation has been so
      difficult to achieve. METHODS: A literature review was undertaken using Medline
      from 1975 to July 2000. Results reported to the International Islet Transplant
      Registry (ITR) up to December 1998 were also analysed. RESULTS: Up to December
      1998, 405 islet allotransplants have been reported the ITR. Of those accurately
      documented between 1990 and 1998 (n = 267) only 12% have achieved insulin
      independence (greater than 7 days). However with refined peri-transplant
      protocols insulin independence at 1 year can reach 20%. CONCLUSIONS: There are
      many factors which can explain the failure of achieving insulin-independence
      after islet allotransplantation. These include the use of diabetogenic
      immunosuppressive agents to abrogate both islet allo-immunity and auto-immunity,
      the critical islet mass to achieve insulin-independence and the detrimental
      effects of transplanting islets in an ectopic site. However recent evidence most
      notably from the Edmonton group demonstrates that islet allotransplantation still
      has great potential to become an established treatment option for diabetic
      patients.

PMID- 11251672
TI  - Limited impact of lifestyle education in patients with Type 2 diabetes mellitus
      and microalbuminuria: results from a randomized intervention study.
AB  - AIMS: To assess the effect of intensified education on lifestyle (diet, exercise
      and smoking) as part of an intensified multifactorial intervention over a 4-year
      period in patients with Type 2 diabetes mellitus with microalbuminuria. METHODS:
      Patients, aged 45-65 years, were randomly assigned either to an intensive group
      focusing on change of behaviour as well as polypharmacological treatment (n = 80)
      or to a control group receiving conventional treatment (n = 80). Diet
      intervention focused on dietary fat and carbohydrate. Food intake was estimated
      by dietary history interviews and nutrients were calculated from food tables.
      Exercise and smoking habits were evaluated by interviews. RESULTS: Mean follow-up
      was 3.8 (SD 0.3) years. The decrease in total fat intake (% of energy intake) was
      larger in the intensive group as compared to the control group (41.2 (6.2) to
      34.2 (6.0) vs. 41.9 (6.5) to 38.3 (6.4)%, P = 0,0001). The decrease in saturated
      fatty acids (% of total fat intake) was from 47 (4) to 44 (6)% with intensive
      therapy vs. 45 (5) to 46 (5)%, P = 0.001 and the increase in polyunsaturated
      fatty acids was from 14 (4) to 18 (6) vs. 16 (5) to 14 (4)%, P < 0.0001. Also the
      increase in carbohydrate was larger with intensive therapy. However, changes in
      exercise and smoking habits did not differ between groups. CONCLUSION: Despite
      the many resources invested in behaviour modification in this study, only modest
      changes were obtained in nutrient intake. Further studies are required to
      determine the best method of inducing long-lasting changes in behaviour in Type 2
      diabetic patients.

PMID- 11251673
TI  - Lipid hydroperoxide and markers of renal disease susceptibility in African
      Caribbean and Caucasian patients with Type 2 diabetes mellitus.
AB  - AIMS: The reasons for the increased incidence of diabetic nephropathy in African
      Caribbean compared with Caucasian subjects are poorly understood. Increased
      oxidative stress is linked to the development of endothelial dysfunction and
      histological abnormalities associated with diabetic renal disease. Therefore, it
      was assessed whether a marker of oxidative stress, lipid hydroperoxide (LOOH) and
      endothelial damage, von Willebrand factor (vWF) varied according to ethnic origin
      in the presence or absence of early diabetic nephropathy. METHODS: Eighty-eight
      patients with Type 2 diabetes mellitus of African-Caribbean or Caucasian origin
      without a history of cardiovascular disease or clinical proteinuria were studied.
      Patients were classified as having microalbuminuria or normal albumin excretion.
      Fasting plasma vWF and LOOH were measured by an inhouse enzyme-linked immunoassay
      and ferrous oxidation with xylenol orange (FOX) assay, respectively. The
      relationship of LOOH to urinary albumin status, the metabolic disturbances of
      diabetes, blood pressure and ethnic origin were assessed using multivariate
      analysis. RESULTS: Compared with Caucasian patients those of African-Caribbean
      origin had higher systolic blood pressure and HDL-cholesterol (157.8 +/- 17.0 vs.
      147.8 +/- 24.4, P = 0.041 and 1.6 +/- 0.4 vs. 1.3 +/- 0.5, P = 0.018) but lower
      total triglycerides (1.3 +/- 0.8 vs. 1.9 +/- 1.1, P = 0.008). LOOH was
      significantly higher in the African-Caribbean patients compared with Caucasians
      (5.98 +/- 2.49 vs. 4.49 +/- 2.19, P = 0.006). vWF tended to be higher in
      microalbuminuric patients but showed no variation with ethnicity. In logistic
      regression analysis, LOOH was the only independent predictor of a raised albumin
      excretion rate (P = 0.008). In multiple regression analysis, African-Caribbean
      ethnicity (P = 0.020) HDL-cholesterol (P = 0.036), total triglycerides (P =
      0.002) and a raised albumin excretion rate (P = 0.002) were independent
      predictors of LOOH. CONCLUSIONS: In this group of Type 2 diabetic patients an
      increase in LOOH is associated with abnormal urinary albumin excretion. African
      Caribbean origin was a determinant of LOOH independently of microalbuminuria. It
      is postulated that increased oxidative stress is of pathophysiological
      significance in accelerating the development of renal disease in African
      Caribbean patients.

PMID- 11251675
TI  - Increased secretion of TGF-beta1 by peripheral blood mononuclear cells from
      patients with Type 1 diabetes mellitus with diabetic nephropathy.
AB  - AIMS: To study transforming growth factor (TGF)-beta1 secretion by peripheral
      blood mononuclear cells (PBMC) from Type 1 diabetic patients with and without
      nephropathy. METHODS: Thirty normoalbuminuric Type 1 diabetic patients (urinary
      albumin excretion rate (AER) < 20 microg/min), 12 microalbuminuric (AER 20-200
      microg/min), 10 nephropathic (AER > 200 microg/min), and 13 non-diabetic
      individuals were recruited. TGF-beta1 secretion by PBMC was measured by enzyme
      immunoassay (EIA) after 48 h culture with and without phytohaemagglutinin (PHA)
      (5 microg/ml). RESULTS: After 48 h culture, the highest TGF-beta1 levels secreted
      by unstimulated PBMC were found in patients with nephropathy (median 6.2 (range
      0.9-20.0) ng/ml) when compared to patients with normal albumin excretion (4.1
      (0.2-11.3) ng/ml), microalbuminuria (1.8 (0.2-6.4) ng/ml) and healthy controls
      (1.0 (0.2-7.0) ng/ml); P = 0.02 for the three diabetic groups and P = 0.006 for
      all groups. At 48 h, the PHA-stimulated TGF-beta1 levels were 12.4 (2.9-30.0)
      ng/ml in nephropathic, 7.3 (0.5-21.2) ng/ml in normoalbuminuric, and 5.5 (0.5
      27.6) ng/ml in microalbuminuric patients (P = 0.05). A correlation was observed
      between TGF-beta1 and diastolic blood pressure in the subgroup of patients with
      incipient and overt nephropathy (r = 0.45, P = 0.04). CONCLUSIONS: Type 1
      diabetic patients with overt nephropathy show increased TGF-beta1 secretion by
      PBMC. Diastolic blood pressure levels correlated with TGF-beta1 secretion in
      diabetic patients with nephropathy. Increased TGF-beta1 secretion by PBMC may be
      associated with renal and vascular disease in Type 1 diabetes mellitus.

PMID- 11251674
TI  - Iohexol as a marker of glomerular filtration rate in patients with diabetes:
      comparison of multiple and simplified sampling protocols.
AB  - AIMS: To report on the reproducibility of iohexol glomerular filtration rate
      (GFR) estimation, to compare the plasma clearance of iohexol with that
      of[51Cr]EDTA and to evaluate the reliability of reduced sampling schedules in
      estimating GFR in Type 1 and Type 2 diabetes mellitus. METHODS: Agreement was
      assessed in 15 Type 1 and 26 Type 2 diabetics with creatinine ranging from 53 to
      564 micromol/l. RESULTS: The regression between multiple-sample iohexol
      and[51Cr]EDTA clearances was 0.999 in Type 1 and 0.987 in Type 2 diabetes (P <
      0.0001 for both). A seven-sample design and the three-sample approach by Brochner
      Mortensen were validated by comparison with the full-sample schedule in 87
      patients (51 Type 1, 36 Type 2). Full-sample GFR was 80.3 +/- 43.8, seven-sample
      79.5 +/- 43.9 (r = 0.990) and three-sample 79.8 +/- 45.2 ml.min-1.1.73 m-2 (r =
      0.972). The coefficients of variation of GFR were 2.7 +/- 1.4% and 3.8 +/- 1.9%
      for the full-sample and the seven-sample approaches, respectively, and
      significantly higher for the three-sample design (6.9 +/- 3.4%, P = 0.0001).
      CONCLUSIONS: After iohexol injection, the Brochner-Mortensen schedule does not
      provide an accurate estimate of GFR. The seven-sample approach gives acceptable
      errors and allows a good estimate of GFR throughout a wide range of renal
      function.

PMID- 11251676
TI  - Increasing prevalence of diabetes mellitus and impaired glucose tolerance among
      60-year-old Danes.
AB  - AIMS: The age-specific prevalence of diabetes mellitus and impaired glucose
      tolerance (IGT) was estimated in 60-year-old individuals in 1996/97 and compared
      to the prevalence in 1974/75. The study also examined whether or not the change
      in prevalence of diabetes and IGT could be explained by changes in body mass
      index (BMI) and physical activity. METHODS: Diabetes and IGT were diagnosed by a
      standardized oral glucose tolerance test (OGTT) in two Danish population-based,
      age-specific, birth cohorts. RESULTS: The prevalence of diabetes in 1996/97 was
      12.3% among 60-year-old men and 6.8% among women, representing an increase in
      diabetes of 58% in men and 21% in women compared to 1974/75. The prevalence of
      IGT was 15.9% among men and 13.1% among women, representing increases of 109 and
      16%, respectively. A concurrent increase in BMI in the 22-year period between the
      two studies explained the increase found in the prevalence of diabetes and IGT.
      CONCLUSIONS: A marked increase in the prevalence of diabetes and IGT among 60
      year-old individuals over a 22-year period was observed - especially in men. The
      increase was fully explained by a concurrent increase in BMI.

PMID- 11251677
TI  - The effects of ulcer size and site, patient's age, sex and type and duration of
      diabetes on the outcome of diabetic foot ulcers.
AB  - AIMS: The outcome of foot ulcers is affected by wound depth, infection, ischaemia
      and glycaemic control. The aim of this study was to determine the effects of
      ulcer size, site, patient's age, sex and type and duration of diabetes on the
      outcome of diabetic foot ulcers. METHODS: Diabetic patients with new foot ulcers
      presenting during a 12-month period had demographics and ulcer characteristics
      recorded at presentation. Ulcers were followed-up until an outcome was noted.
      RESULTS: One hundred and ninety-four patients (77% males) with a mean (+/- SD)
      age and duration of diabetes of 56.6 +/- 12.6 and 15.4 +/- 9.9 years,
      respectively, were included in the study. The majority of ulcers were neuropathic
      (67.0%) and present on the forefoot (77.8%) with a median (interquartile range)
      area of 1.5 (0.6-4.0) cm2. Amputations were performed for 15% of ulcers; 65%
      healed; 16% remained unhealed and 4% of patients died. The median (95% confidence
      interval) time to healing was 10 (8.8-11.6) weeks. Ulcer area at presentation was
      greater in the amputation group compared to healed ulcers (3.9 vs. 1.2 cm2, P <
      0.0001). Ulcer area correlated with healing time (rs = 0.27, P < 0.0001) and
      predicted healing (P = 0.04). Patient's age, sex, duration/type of diabetes, and
      ulcer site had no effect on outcome. CONCLUSIONS: Ulcer area, a measure of ulcer
      size, predicts the outcome of foot ulcers. Its inclusion into a diabetic wound
      classification system will make that system a better predictor of outcome.

PMID- 11251678
TI  - Microalbuminuria in patients with Type 2 diabetes mellitus from general practice:
      course and predictive value.
AB  - AIMS: To assess the course of microalbuminuria in patients with Type 2 diabetes
      mellitus in general practice and the predictive value of urinary albumin
      concentration on all-cause mortality, cardiovascular mortality and cardiovascular
      morbidity. METHODS: Cohort study in Type 2 diabetic patients tested for
      microalbuminuria in 1992, and re-tested in 1998. During follow-up all
      cardiovascular morbidity and mortality were recorded. RESULTS: Of the original
      sample of 317 patients, 163 patients were re-tested. The mean change in urinary
      albumin concentration was +16.2 mg/l (range -122.0 to +602 mg/l). Seventy-five
      per cent of the patients without microalbuminuria in 1992 still had no
      microalbuminuria in 1998 and 40% of those with microalbuminuria in 1992 reverted
      to normoalbuminuria in 1998. Cox survival analysis, stratified for age, showed
      that microalbuminuria at baseline resulted in a risk ratio of all-cause mortality
      of 1.4 (95% confidence interval 0.8-2.7), of cardiovascular mortality of 1.2 (0.5
      2.8) and of new cardiovascular events (including cardiovascular mortality) of 1.4
      (0.8-2.3). CONCLUSIONS: In the majority of patients the change of urinary albumin
      excretion was small, but the range was wide. A weak non-significant relationship
      between microalbuminuria and all-cause mortality and cardiovascular morbidity was
      observed.

PMID- 11251679
TI  - No reactive hypoglycaemia in Type 2 diabetic patients after subcutaneous
      administration of GLP-1 and intravenous glucose.
AB  - AIMS: It has previously been shown that intravenous and subcutaneous
      administration of glucagon-like peptide (GLP)-1 concomitant with intravenous
      glucose results in reactive hypoglycaemia in healthy subjects. Since GLP-1 is
      also effective in Type 2 diabetic patients and is presently being evaluated as a
      therapeutic agent in this disease, it is important to investigate whether GLP-1
      can cause hypoglycaemia in such patients. METHODS: Eight Type 2 diabetic patients
      (age 54 (49-67) years; body mass index 31 (27-38) kg/m2; HbA1c 9.4 (7.0-12.5)%)
      and seven matched non-diabetic subjects (HbA1c 5.5 (5.2-5.8)%, fasting plasma
      glucose 5.4 (5.0-5.7) mmol/l) were given a subcutaneous injection of 1.5 nmol GLP
      1/kg body weight (maximally tolerated dose), and 15 min later, plasma glucose
      (PG) was raised to 15 mmol/l with an intravenous glucose bolus. RESULTS:
      Hypoglycaemia with a PG at or below 2.5 mmol/l was seen in five of the seven
      healthy subjects after 60-70 min, but PG spontaneously increased again, reaching
      3.7 (3.3-4.0) mmol/l at 90 min. In the patients, PG fell slowly and stabilized at
      8.6 (4.2-12.1) mmol/l after 80 min. In both groups, glucagon levels initially
      decreased, but later increased, exceeding basal levels in healthy subjects, in
      spite of persistent, high concentrations of GLP-1 (P < 0.02). CONCLUSIONS:
      Subcutaneous GLP-1 plus intravenous glucose induced reactive hypoglycaemia in
      healthy subjects, but not in Type 2 diabetic patients. Therefore, a GLP-1-based
      therapy would not be expected to be associated with an increased risk of
      hypoglycaemia in Type 2 diabetes mellitus.

PMID- 11251680
TI  - Glycaemia and insulinaemia in elderly European subjects (70-75 years).
AB  - AIMS: To determine glycaemia and insulinaemia in elderly subjects aged 70-75
      years, living across Europe, who participated in the EURONUT-SENECA (Survey in
      Europe on Nutrition and the Elderly, a Concerted Action) study. METHODS: Fasting
      plasma glucose (FPG) and fasting insulin concentrations were measured in 1830
      subjects aged 70-75 years living in 15 traditional towns in 11 European
      countries. For the diagnosis of diabetes, the recommendations of the 1997 report
      of the American Diabetes Association 'Expert Committee on the diagnosis and
      classification of diabetes mellitus' were used. RESULTS: A total of 31.6% of the
      study subjects had either diabetes (17.5%) or impaired fasting plasma glucose
      (FPG) (14.1%). Fifty-one per cent of the subjects with diabetes were unaware of
      the disease. No difference in diabetes prevalence was found for sex, but male
      subjects were more likely to have impaired FPG than female subjects (16.8 vs.
      11.5%, P = 0.001). Hyperinsulinaemia (fasting insulin levels in the highest
      quartile) was associated with increased FPG, body mass index, and waist-to-hip
      ratio. CONCLUSIONS: It was found that a substantial number of elderly Europeans
      have impaired glucose homeostasis, with diabetes and impaired FPG being present
      in almost a third of European subjects aged 70-75 years.

PMID- 11251681
TI  - What attracts patients with diabetes to an internet support group? A 21-month
      longitudinal website study.
AB  - AIMS: To establish and evaluate a web-based educational and emotional resource
      for patients with diabetes and their family members. METHODS: A total of 47 365
      user visits over a 21-month period to three internet discussion groups about
      diabetes were tracked for user activity, characteristics and level of
      satisfaction. RESULTS: The primary domains of users were the US (70%) and Canada
      (4%). Of all users, 7.55% posted messages, while 92.45% read messages posted by
      others. The average length of use was 15 min 5 s. Forty-four per cent posted
      messages to the nutrition discussion, 38% posted messages to the motivational
      discussion, and 18% posted messages to the family discussion. The most common
      postings addressed nutrition (42%), the emotional impact of diabetes (18%),
      managing high or low blood glucose levels (10%), and complications (8%).
      Respondents to the satisfaction survey were 64% female, 43% were insulin and 37%
      non-insulin users. Eighty-four per cent were older than 30 years, 34% had
      recently diagnosed diabetes and 32% had diabetes > 10 years. Forty-three per cent
      visited more than three times. Seventy-nine per cent of all respondents rated
      participation in the chat as having a positive effect on coping with diabetes.
      CONCLUSIONS: A professionally moderated internet discussion group is actively
      visited by a broad base of patients and families, and appears to be a useful
      strategy for engaging patients with chronic disease for emotional support and
      information exchange.

PMID- 11251682
TI  - Beta blocker prescribing differences in patients with and without diabetes
      following a first myocardial infarction.
AB  - AIMS: To document the prescribed usage of beta blockers in patients with and
      without diabetes mellitus discharged from hospital following a first myocardial
      infarction. METHODS: All patients with diabetes and a group of patients matched
      for age and sex without diabetes, admitted with a documented first myocardial
      infarction during the period 1995-1999 at the Royal Liverpool University
      Hospital, Liverpool, UK were audited. RESULTS: Data were available on 201
      patients with diabetes and 199 patients without diabetes. No significant
      differences existed between the diabetic and non-diabetic groups for age and sex.
      Twenty-three per cent of patients with diabetes were prescribed a beta blocker
      compared to 52% of non-diabetic patients (P < 0.01). Patients with diabetes had a
      higher frequency of perceived contraindications than patients without diabetes
      (36 vs. 27%, P < 0.001). Thirty-five per cent of patients with diabetes and 18%
      of non-diabetic patients had no contraindication to the use of beta blocker but
      were not prescribed one (P < 0.001). CONCLUSIONS: Although beta blockers can
      provide useful benefits in patients with diabetes following a myocardial
      infarction, this study suggests that a significant proportion of patients with
      diabetes and without a contraindication to treatment are still not receiving beta
      blockers after myocardial infarction.

PMID- 11251683
TI  - Reducing hospital inpatient length of stay for patients with diabetes.
AB  - AIMS: To ascertain the effect of routine review by a diabetes nurse advisor on
      length of stay for medical and surgical inpatients with diabetes. METHODS:
      Inpatients with diabetes were identified prospectively from January 1997 until
      December 1998 (792 in 1997 and 819 in 1998). A new post of diabetes nurse advisor
      was introduced in January 1998 to optimize diabetes management. Length of stay
      was calculated retrospectively from hospital computer records. RESULTS: Median
      length of stay in 1997 was 11 days in medicine and 8 days in surgery. In 1998,
      the nurse advisor made 1936 visits to 819 patients; median length of stay fell to
      8 days in medicine and 5 days in surgery (P < 0.001). Bed occupancy by patients
      with diabetes fell from 6.8 to 4.0%. Mean length of stay across the hospital
      remained unchanged. CONCLUSIONS: The introduction of a ward-based diabetes nurse
      advisor was associated with significant reductions in length of stay in
      inpatients with diabetes. Since this study was not a randomized study, other
      factors may have contributed to this change. However, the consistency of the
      reduction across specialities suggests the post itself had an important effect.

PMID- 11251684
TI  - 'Human' and animal insulin compared--a thorough comparison?

PMID- 11251686
TI  - Analysis of methods of ocular examination in screening for diabetic retinopathy.

PMID- 11251688
TI  - Mouse cytokine gene nucleotide sequence alignments, 2000. Part III.

PMID- 11251689
TI  - DRB1 alleles in polymyalgia rheumatica and rheumatoid arthritis in southern
      France.
AB  - To investigate the association of HLA-DRB1 alleles with polymyalgia rheumatica
      (PMR) and rheumatoid arthritis (RA), 55 patients with PMR without giant cell
      arteritis, 203 patients with RA and 230 controls, all from the European
      population of Marseille, were HLA-DRB1 genotyped by PCR-SSO. HLA-DRB1*01 was
      significantly increased in both the PMR and RA groups compared to controls (35%
      versus 17%, P(c) < 0.05, and 41% versus 17%, P(c) < 0.001, respectively). HLA
      DRB1*04 was significantly increased in the RA group compared to controls (48%
      versus 23%, P(c) < 0.001) but not in the PMR group. HLA-DRB1*04 subtype
      frequencies were significantly different between PMR patients and RA patients.
      Shared epitope-positive HLA-DRB1*04 alleles (DRB1*0401, 0404, 0405, 0408) were
      significantly overrepresented in RA patients compared to PMR patients and shared
      epitope-negative HLA-DRB1*04 alleles were overrepresented in PMR patients
      compared to RA patients. In conclusion, in the Mediterranean population studied,
      HLA-DRB1*01 is associated with RA and PMR whereas HLA-DRB1*04 is associated with
      RA only.

PMID- 11251690
TI  - Association of vitamin D receptor genotypes with early onset rheumatoid
      arthritis.
AB  - The presence of certain vitamin D receptor (VDR) genotypes has been associated
      with low bone mineral density (BMD) in elderly populations as well as with
      accelerated bone loss in patients with rheumatoid arthritis (RA). In the present
      study, VDR genotypes from 120 Spanish patients with RA were investigated. Three
      VDR gene polymorphisms (BsmI, ApaI and TaqI) were investigated using polymerase
      chain reaction followed by enzymatic digestion. The distributions of VDR allelic
      frequencies were similar in patients and controls and therefore no influence of
      VDR polymorphisms on rheumatoid arthritis susceptibility could be demonstrated.
      However, in an analysis of the clinical features of the different VDR-related
      genetic subgroups, the BB/tt genotype, defined by the BsmI and TaqI restriction
      site polymorphisms, was identified to be weakly associated with an early onset RA
      in female patients. This VDR genotype has been associated with a low BMD level in
      various studies. When patients were stratified according to the presence of the
      shared HLA epitope SE, it was found that SE + female patients bearing the BB/tt
      genotype showed the earliest disease onset. The mechanisms by which the VDR
      polymorphism is associated with RA is unknown, but they could be related to the
      immunoregulatory properties of vitamin D.

PMID- 11251691
TI  - A single nucleotide polymorphism at position --109 of the RANTES proximal
      promoter.

PMID- 11251693
TI  - Nomenclature for factors of the HLA System, update August 2000.

PMID- 11251692
TI  - A new coding region polymorphism of human IgLC2.
AB  - A new allelic form of the human IgLC2 gene is described. The marker involves a T
      to C substitution in the C lambda 2 constant region gene, a silent substitution
      at amino acid coding position 178 (YAASSYLSL) and two substitutions in the 3'
      flanking region. Analysis of IgLC2 alleles in a total of 60 individuals has
      indicated a frequency of 0.32 for the new allele, which has been designated
      IgLC2*B2. The *B1 and *B2 alleles encode T and C, respectively, at nucleotide
      position 212 in the IgLC2 coding region. Both the *B1 and *B2 alleles are found
      in individuals homozygous for the single-copy RFLP allele of IgLC2/IgLC3 (8 kb
      EcoRI). Knowledge of alleles of this marker will be important for studies on the
      expression of the IgLC2 and IgLC3 isotypes in normal and autoimmune lymphocyte
      populations, as the coding regions of the two isotypes differ only at this
      position. The marker will also be useful in further studies of linkage with other
      IgLV and IgLC markers and to establish possible correlations with susceptibility
      to autoimmune disorders.

PMID- 11251694
TI  - Nomenclature for factors of the HLA System, update September 2000.

PMID- 11251695
TI  - Efficacy of gabapentin in migraine prophylaxis.
AB  - OBJECTIVE: To compare gabapentin with placebo for use as a prophylactic agent in
      patients with migraine (with or without aura). STUDY DESIGN AND TREATMENT: After
      screening, a 4-week, single-blind, placebo baseline period was followed by a 12
      week, double-blind, treatment period. The 12-week treatment period consisted of a
      4-week titration phase and an 8-week stable-dosing phase. During the 4-week
      titration phase, patients were started on one 300-mg capsule of gabapentin or
      matching placebo. Patients were titrated weekly from 900 mg/day (end of week 1)
      to 2400 mg/day (end of week 4) and had to be receiving a stable dose of study
      medication by the end of the titration period. Study medication was to be given
      on a three-times-a-day dosing regimen. METHODS: The study hypothesis was defined
      a priori as a lower 4-week migraine rate during the second stabilization period
      for the gabapentin-treated patients as compared with the placebo-treated
      patients. The analyses were performed with the 4-week migraine rate at baseline
      as a covariate and center as a blocking factor. RESULTS: At seven participating
      centers, 143 patients with migraine were randomized in a 2:1 ratio and received
      either gabapentin (n = 98) or matching placebo (n = 45). Thirty-three patients
      (24.1%) discontinued prematurely from the study, including 24 (24.5%) of 98
      gabapentin-treated patients and 9 (20.0%) of 45 placebo-treated patients; the
      majority of patients discontinued due to adverse events (16 [16.3%] of 98
      gabapentin-treated patients; 4 [8.9%] of 45 placebo-treated patients). Patients
      included in the analysis were evenly balanced for age, sex, race, weight, and
      height. The majority of these patients were white (80 [92.0%] of 87) and women
      (72 [82.8%] of 87), with a mean age of approximately 39.4 years and a history of
      migraine episodes for a mean of about 21 years. At the end of the 12-week
      treatment phase, the median 4-week migraine rate was 2.7 for the gabapentin
      treated patients maintained on a stable dose of 2400 mg/day and 3.5 for the
      placebo-treated patients (P =.006), compared with 4.2 and 4.1, respectively,
      during the baseline period. Additionally, 26 (46.4%) of 56 patients receiving a
      stable dose of 2400 mg/day gabapentin and 5 (16.1%) of 31 patients receiving
      placebo showed at least a 50% reduction in the 4-week migraine rate (P =.008).
      The average number of days per 4 weeks with migraine was also statistically
      significant and favored gabapentin (P =.006) during stabilization period 2. The
      median change in 4-week headache rate was statistically significant as well (P
      =.013). The most frequently reported adverse events for both treatment groups
      were asthenia, dizziness, somnolence, and infection. Adverse events determined by
      the investigator to be associated with study drug resulted in patient withdrawal
      in 13 (13.3%) of 98 gabapentin-treated patients and 3 (6.7%) of 45 placebo
      treated patients. Somnolence and dizziness accounted for many of the premature
      withdrawals among those taking gabapentin. CONCLUSION: Gabapentin is an effective
      prophylactic agent for patients with migraine. In addition, gabapentin appears
      generally well tolerated with mild to moderate somnolence and dizziness.

PMID- 11251696
TI  - Deficiency of tumor necrosis factor alpha in a subclass of menstrual migraineurs.
AB  - OBJECTIVE: The objective of this study was to determine whether differences in
      urinary proinflammatory cytokines, interleukin-1beta (IL-1beta), interleukin-6
      (IL-6), and tumor necrosis factor alpha (TNF-alpha), exist between migraineurs
      and nonheadache control subjects, and between nonhormonal migraine and menstrual
      migraine. Any differences noted would expand and clarify a neuroimmune hypothesis
      of migraine pathogenesis and lead to future diagnostic markers or therapeutic
      options or both for the disorder. BACKGROUND: Current theories of migraine
      pathogenesis focus on biochemical abnormalities in the central nervous system
      resulting in sterile inflammation of meningeal blood vessels. Vasoactive
      substances involved in this process may include substance P, calcitonin gene
      related peptide, neurokinin A, serotonin, and nitric oxide. Immune cell products,
      such as histamine, leukotrienes, and cytokines, also have vascular inflammatory
      properties. METHODS: A study of proinflammatory cytokines, IL-1beta, IL-6, and
      TNF-alpha, was undertaken in menstrual migraineurs. During and outside of menses,
      24-hour urine samples of 19 women with migraine were taken during a menstrual
      migraine, a nonmenstrual migraine, and a headache-free day, and compared with 24
      hour urine samples taken of 10 nonheadache controls during and outside of menses.
      RESULTS: A neuroimmune mechanism for migraine was tested with expected increases
      in proinflammatory cytokines tested during a migraine. This hypothesis was not
      validated. Mean IL-6 levels were increased in all three samples of migraineurs
      versus controls, but did not achieve statistical significance. No differences
      were found in IL-1beta levels between samples. Interestingly, marked differences
      were found in TNF-alpha values in menstrual migraineurs. Twelve (63%) of 19
      migraineurs had at least one urine sample with undetectable TNF-alpha levels,
      whereas none of the 20 samples given by the 10 nonheadache controls in this study
      had undetectable levels. Thirty-two samples from men with cluster headache and
      nonheadache control subjects in prior studies had detectable levels. CONCLUSIONS:
      This deficiency of TNF-alpha levels in women with migraine may signal a
      disordered neuroimmune communication network and predisposition to migraine.

PMID- 11251698
TI  - Recovery cycle of the blink reflex and exteroceptive suppression of temporalis
      muscle activity in migraine and tension-type headache.
AB  - Brain stem interneuronal excitability can be assessed by recording the recovery
      cycle of the blink reflex and exteroceptive suppression of temporalis muscle
      activity. Abnormal endogenous pain control mechanisms due to disturbed brain stem
      interneuronal activity have been implicated in the pathogenesis of tension-type
      headaches. The blink reflex, exteroceptive suppression of temporalis muscle
      activity, and the recovery curve of both the R2 component of the blink reflex and
      the ES2 component of the exteroceptive suppression of the temporalis muscle
      activity were studied in 20 patients with migraine without aura, 32 patients with
      tension-type headache, and 20 normal controls. In our study, the blink reflex was
      elicited by stimulation of the supraorbital nerve; the exteroceptive suppression
      of the temporalis muscle activity was elicited by applying electrical shocks to
      the labial commissure, both on the lower and upper sides. The recovery cycle was
      established by delivering paired shocks at different interstimulus intervals.
      Comparisons were made between normal control subjects, patients with migraine
      without aura, and patients with tension-type headache. The latency of R1, R2, and
      R2', the amplitude and size of the R2 and R2' components of the blink reflex, the
      latency and duration of the ES1 and ES2 components, and the recovery curve of the
      ES2 component of the temporalis muscle activity did not differ between groups.
      However, the recovery curve of the R2 component of the blink reflex diminished in
      patients with tension-type headache compared with the other groups. Our findings
      indicate reduced excitability of the brain stem interneurons in patients with
      tension-type headache.

PMID- 11251697
TI  - Direct superoxide scavenging activity of nonsteroidal anti-inflammatory drugs:
      determination by electron spin resonance using the spin trap method.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs), which are used widely to manage
      pain, are known to inhibit cyclooxygenase, but details of the mechanisms of NSAID
      action remain unclear. We investigated the ability of three NSAIDs (indomethacin,
      loxoprofen, and etodolac) to eliminate and inhibit free radicals. Superoxide
      scavenging activity of these NSAIDs was measured in vitro by electron spin
      resonance spectrometry using 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) as a spin
      trap. Electron spin resonance demonstrated that formation of superoxide-DMPO spin
      adduct was completely inhibited by two nonselective cyclooxygenase inhibitors,
      indomethacin (3 mmol) and loxoprofen (3 mmol). The electron spin resonance study
      also demonstrated that the formation of superoxide-DMPO spin adduct was strongly
      inhibited by a selective cyclooxygenase-2 inhibitor, etodolac, in a concentration
      dependent manner. These results indicate that NSAIDs, including indomethacin,
      loxoprofen, and etodolac, have direct superoxide scavenging activity.

PMID- 11251699
TI  - Development of a brief 24-hour adolescent migraine functioning questionnaire.
AB  - The objective was to develop a brief questionnaire to assess short-term
      functioning decrements in adolescents with acute migraine. One hundred twenty
      three potential items were generated by literature review and by interviewing
      adolescent migraineurs and migraine specialists. To reduce the items, 127
      adolescents were asked to identify which items affected their daily functioning
      in the 24 hours following onset of a migraine, and to rate them on a 5-point
      scale from "not very important" to "extremely important." Reduction to an 18-item
      questionnaire was performed by evaluating subject-perceived importance (number of
      times an item was chosen times mean importance score) in combination with
      principal components factor analysis. Five domains were identified: (1)
      activities, (2) social functioning, (3) cognitive functioning, (4) migraine
      headache symptoms, and (5) emotional functioning. Questions regarding school loss
      and school performance during a migraine were added to the final questionnaire as
      a separate outcome measure. The correlation between the five domains as measured
      by the Spearman correlation coefficient ranged from 0.17 to 0.49 suggesting some,
      but minimal, overlap. Cronbach alpha for individual domains ranged from.50 to.84.
      The questionnaire was pilot-tested in 12 adolescent migraineurs to determine ease
      of administration and comprehension and revised to improve clarity.

PMID- 11251700
TI  - Spontaneous oscillations in cerebral blood flow velocity give evidence of
      different autonomic dysfunctions in various types of headache.
AB  - OBJECTIVES: Our objectives were to determine if: (1) patients with migraine have
      B wave abnormalities in comparison to normal controls and patients with chronic
      tension headache and (2) patients with chronic tension headache have an imbalance
      in autonomic activity that is reflected in differences in Mayer wave activity in
      comparison to normal controls. BACKGROUND: B waves and Mayer waves are
      spontaneous oscillations in cerebral blood flow velocity with a frequency of 0.5
      to 3 or 4 to 7 cycles per minute, respectively, and can be measured by
      transcranial Doppler sonography. There is experimental evidence that B waves are
      generated by certain brain stem nuclei which modulate the lumen of the small
      intracerebral vessels via monoaminergic nerve endings. In contrast, Mayer waves
      in cerebral blood flow velocity have no central generator but mirror the Mayer
      waves in arterial blood pressure which represent peripheral autonomic activity.
      Migraine may be attributed to a neurotransmitter imbalance in brain stem nuclei.
      Dysfunctions of the peripheral autonomic nervous system are known in patients
      with chronic tension headache. METHODS: Using bilateral transcranial Doppler
      monitoring of the middle cerebral artery B waves and Mayer waves were studied in
      30 patients with migraine without aura, 28 subjects with tension-type headache,
      and 30 normal controls. Coefficient of variation as a quantitative parameter for
      amplitude of waves and the mean frequency were calculated from the envelope
      curves of the Doppler spectra. RESULTS: The coefficient of variation of B waves
      was higher in migrainous patients compared with patients with tension-type
      headache and normal controls (P<.05), indicating an increase in activity of brain
      stem nuclei in migraine only. Patients with chronic tension headaches had lower
      values for Mayer wave activity in comparison with normal controls (P<.05), a sign
      of an impairment of sympathetic activity. CONCLUSIONS: Our data support the
      dysfunction of the brain stem monoaminergic/serotonergic system in migraine. In
      contrast, patients with chronic tension headache have an autonomic dysfunction of
      peripheral origin presenting as a decrease of sympathetic activity.

PMID- 11251701
TI  - Perceived headache associations in Singapore: results of a randomized national
      survey.
AB  - We attempted to discern commonly perceived associations between headache
      symptomatology and various clinical and social parameters based on the results of
      a nationwide randomized survey involving 2096 respondents. A questionnaire
      incorporating demographic data, headache characteristics, and management as well
      as basic health screening was administered by trained interviewers to those aged
      12 years and older. A digital semiautomated blood pressure monitor, a Snellen
      chart, and urinalysis sticks were used to gather clinical information. Elevated
      blood pressure, poor visual acuity, and fewer hours of nightly sleep did not
      positively correlate with headaches of increased frequency, intensity, or
      duration. On the contrary, an age-dependent negative trend was observed with
      regard to blood pressure and visual acuity. Individuals who performed shift work
      had more frequent, although not more intense or long-lasting, headaches. Income
      had no effect on headache prevalence or severity. Our findings are at variance
      with common perceptions of headache in the region. They highlight the need for
      informed counseling of patients presenting to medical attention with headaches
      and suggest that serious intracranial disease should be excluded in atypical
      headaches even if perceived associations are present.

PMID- 11251702
TI  - Efficacy of intravenous magnesium sulfate in the treatment of acute migraine
      attacks.
AB  - OBJECTIVE: To study the efficacy and tolerability of 1 g of intravenous magnesium
      sulfate as acute treatment of moderate or severe migraine attacks. BACKGROUND:
      Migraine is a common disorder in which not only the pain but also the
      accompanying symptoms such as nausea and vomiting reduce activity and
      productivity of sufferers. Many drugs used for the treatment of acute migraine
      attacks have many side effects, are not well tolerated, are ineffective in some
      patients, or cannot be used during pregnancy or in patients with ischemic heart
      disease. Magnesium deficiency has been proposed to play a role in the
      pathophysiology of migraine, and recently treatment of migraine with magnesium
      has gained considerable interest. METHODS: This was a randomized, single-blind,
      placebo-controlled trial including 30 patients with moderate or severe migraine
      attacks. Fifteen patients received 1 g intravenous magnesium sulfate given over
      15 minutes. The next 15 patients received 10 mL of 0.9% saline intravenously.
      Those in the placebo group with persisting complaints of pain or nausea and
      vomiting after 30 minutes also received 1 g magnesium sulfate intravenously over
      15 minutes. The patients were assessed immediately after treatment, and then 30
      minutes and 2 hours later. Intensity of pain, accompanying symptoms, and side
      effects were noted. RESULTS: All patients in the treatment group responded to
      treatment with magnesium sulfate. The pain disappeared in 13 patients (86.6%); it
      was diminished in 2 patients (13.4%); and in all 15 patients (100%), accompanying
      symptoms disappeared. In the placebo group, a decrease in pain severity but
      persisting nausea, irritability, and photophobia were noted in 1 patient (6.6%).
      Accompanying symptoms disappeared in 3 patients (20%) 30 minutes after placebo
      administration. All patients initially receiving placebo were subsequently given
      magnesium sulfate. All of these patients responded to magnesium sulfate. In 14
      patients (93.3%), the attack ended; in 1 patient (6.6%), pain intensity
      decreased; and in all 15 patients (100%), accompanying symptoms disappeared. Both
      the response rate (100% for magnesium sulfate and 7% for placebo) and the pain
      free rate (87% for magnesium sulfate and 0% for placebo) showed that magnesium
      sulfate was superior to placebo. Twenty-six patients (86.6%) had mild side
      effects which did not necessitate discontinuing treatment during magnesium
      sulfate administration. CONCLUSION: Our results show that 1 g intravenous
      magnesium sulfate is an efficient, safe, and well-tolerated drug in the treatment
      of migraine attacks. It is possible that magnesium sulfate could be used in a
      broader spectrum of patients than other drugs commonly used for attack treatment.
      In view of these results, the effect of magnesium sulfate in acute migraine
      should be examined in large-scale studies.

PMID- 11251703
TI  - Amitriptyline treatment in chronic drug-induced headache: a double-blind
      comparative pilot study.
AB  - OBJECTIVE: To assess the effects of amitriptyline and sudden analgesic withdrawal
      on headache frequency and quality of life in patients suffering from chronic
      daily headache related to analgesics abuse. METHODS: Seventeen nondepressed
      patients with chronic drug-induced headache were included in a 9-week, parallel
      group, randomized, double-blind, placebo-controlled study. After abrupt analgesic
      withdrawal, amitriptyline or an active placebo (trihexyphenidyl) was started. The
      primary efficacy variable was headache frequency recorded on a headache diary in
      the last 4 weeks of each treatment. The secondary efficacy variable was quality
      of life (Nottingham Health Profile). RESULTS: Headache frequency decreased by 45%
      in the amitriptyline group and by 28% in the trihexyphenidyl group. Amitriptyline
      enhanced all the dimensions of quality of life and significantly improved
      emotional reaction and social isolation. CONCLUSION: This pilot study suggests a
      beneficial effect of amitriptyline on headache frequency and quality of life for
      patients with chronic drug-induced headache.

PMID- 11251705
TI  - Daily migraine with visual aura associated with an occipital arteriovenous
      malformation.
AB  - A 51-year-old woman with daily attacks of migraine with visual aura is described.
      The aura always occurred on the right and the headache always on the left side of
      the head, suggesting a structural lesion in the left occipital lobe. The lesion
      appeared to be an arteriovenous malformation of which almost full obliteration
      resulted in a decrease in frequency of the aura and in intensity of the headache.
      Subsequent treatment of borderline hypothyroidism with levothyroxine brought
      about a dramatic improvement in frequency of both the aura and the headache. The
      case is discussed in the light of our present understanding of the pathogenesis
      of the migraine attack.

PMID- 11251704
TI  - Extending the efficacy of a thermal biofeedback treatment package to the
      management of tension-type headaches in children.
AB  - This study explored the efficacy of a thermal biofeedback treatment package as an
      intervention with children with tension-type headaches. In a within-subject, time
      lagged, multiple baseline design, five children, aged 8 to 14 years, were
      assigned to baselines of varying lengths prior to receiving treatment. Treatment
      was introduced sequentially across subjects and involved six thermal biofeedback
      treatment visits. Parents were also given guidelines for how best to encourage
      children to independently use the biofeedback skills. Data confirm that the
      participants learned the handwarming skill, practiced the skill on a regular
      basis during treatment, and independently used the skills to manage their pain.
      All participants demonstrated clinically significant reductions in one or more
      headache parameters (frequency, duration, intensity) following treatment. At 6
      month follow-up, four of the five participants were headache-free. Although the
      thermal biofeedback treatment package was generally effective for these children
      with tension-type headaches, the specific type of headache experienced by each
      child appeared to influence the specific response to treatment. In addition, no
      single measure of headache activity was the best indicator of response to
      treatment. The efficacy of the thermal biofeedback treatment package is supported
      as an alternative treatment for children suffering from tension-type headaches.

PMID- 11251706
TI  - Hypertensive encephalopathy presenting with thunderclap headache.
AB  - A 68-year-old woman presented with thunderclap headache, which led to a search
      for subarachnoid hemorrhage. Both computerized tomography of the head and
      cerebrospinal fluid examination were normal. Magnetic resonance imaging revealed
      abnormalities in the white matter in the parieto-occipital regions. There was no
      aneurysm on magnetic resonance angiography. Treatment of hypertension led to
      resolution of the posterior leukoencephalopathy. Hypertensive encephalopathy with
      reversible posterior leukoencephalopathy can present as a thunderclap headache.

PMID- 11251707
TI  - Migrainous aura versus transient ischemic attack in an elderly migraineur.
AB  - In older patients with migraine, the distinction between a migrainous aura and a
      transient ischemic episode can be difficult, as this case illustrates.

PMID- 11251708
TI  - Should you screen for an aneurysm in a migraineur whose mother died from a
      ruptured intracranial saccular aneurysm?

PMID- 11251709
TI  - Sumatriptan: what do we know about fetal risks?

PMID- 11251710
TI  - Cervicogenic headache: a common cause of chronic daily headache.

PMID- 11251712
TI  - Sporadic hemiplegic migraine and Sturge-Weber syndrome.

PMID- 11251713
TI  - Butterscotch masks the bitter taste of sumatriptan nasal spray.

PMID- 11251714
TI  - Postnatal depression -- biological or cultural? A comparative study of postnatal
      women in the UK and Taiwan.
AB  - AIM: The aim of the study was to compare the factors which are associated with
      postnatal depression in the UK (United Kingdom) and Taiwan. BACKGROUND/RATIONALE:
      A comparative study of postnatal women in the UK and Taiwan was undertaken to
      investigate postnatal care and the prevalence of postnatal depression.
      DESIGN/METHODS: The Edinburgh Postnatal Depression Scale (EPDS) was used to
      determine the prevalence of postnatal depression. A semistructured interview and
      validated questionnaire were used to collect data on maternal satisfaction with
      postnatal care and the factors associated with postnatal depression. A one in
      three random sample of women from two community midwife teams in Sheffield, UK
      and three public health stations in Keelung, Taiwan took part in the study.
      RESULTS/FINDINGS: Fifty (94% response rate) women from Sheffield and 101 (83%
      response rate) women from Keelung, who were at low risk for maternal or foetal
      problems during labour and the postnatal period, agreed to participate. The
      prevalence of postnatal depression in the British and Taiwanese women was almost
      equal; 18% in the UK and 19% in Taiwan. In Taiwan, the prevalence of postnatal
      depression had a negative association with relationship with partner (Spearman
      correlation=-0.34, P < 0.001) and self-confidence (Spearman correlation=-0.28, P
      < 0.01, Spearman correlation). In addition Taiwanese women who felt more anxious
      after birth (10.9 +/- 7.9, P < 0.001, t-test) had a higher chance of postnatal
      depression. In the UK, there was a significant negative association between
      adaptation to the new role of motherhood and score on the EPDS (Spearman
      correlation=-0.47, P < 0.001). The overall scores for maternal satisfaction were
      28.1 and 24.3 in the UK and Taiwan, respectively (P < 0.001, t-test). British
      women reported a better quality of care during the postnatal period in terms of
      emotional support and physical care. CONCLUSIONS: The findings of this study
      suggest that further cross cultural investigation could shed light on the
      relative balance of biological and cultural factors which may be associated with
      the onset of postnatal depression. As the prevalence of postnatal depression is
      similar in both cultures despite large differences in culture and postnatal care
      systems, some support is given to a hypothesis that postnatal depression has at
      least some biological determinants as well as cultural/social ones.

PMID- 11251715
TI  - Stories seldom told: paediatric nurses' experiences of caring for hospitalized
      children with special needs and their families.
AB  - AIMS OF THE STUDY: This study explored paediatric nurses' experiences of caring
      for children with special needs and their families in an acute care setting. The
      aim of the study was to increase understanding of nurses' experiences of caring
      for these children and their families. The study was designed to reveal the
      caring practices embedded within these relationships through exploring nurses'
      stories. STUDY DESIGN/METHODS: Gadamerian hermeneutic phenomenology and feminist
      research principles were the approaches used to guide the study. Interviews were
      held with experienced paediatric nurses and interpretation of interview
      transcripts using a Gadamerian hermeneutic phenomenological approach resulted in
      the identification of four themes. FINDINGS: The four themes revealed were:
      Special Relationships; Multiple Dimensions of Who is Expert; Development of Trust
      Between Nurses and Families; and Feelings of Frustration and Guilt. CONCLUSIONS:
      The study emphasized the context-specific nature of relationships between nurses
      and children and their families. The nurses spoke about the difficulties they
      encountered in their practice and some of the ways that they dealt with these
      problems. They discussed the things that they valued and those that made them
      feel guilty and frustrated. In doing so, they revealed their warmth, strength,
      humanity and caring.

PMID- 11251716
TI  - The paediatric diabetes specialist nurse and diabetes education in childhood.
AB  - AIMS OF THE STUDY: The aim of this study was to identify the job title, work
      setting, qualifications and training of the paediatric diabetes specialist nurse
      (PDSN) as well as to examine the composition of the multidisciplinary diabetes
      team. It also aimed to determine who is involved in diabetes education and to
      explore the teaching methods, approaches, tools and materials that the PDSN uses
      in the educational process. DESIGN AND METHODS: A survey design was used.
      Questionnaires, which combined quantitative and qualitative approaches, were sent
      to 80 participants from eight opportunistically selected regions of the United
      Kingdom (UK). Access to names and addresses was gained through the directory of
      diabetes specialist nurses (DSNs). The selection criteria were nurses working
      full-time with children with diabetes or having children with diabetes on their
      caseloads. The overall response rate was 66 (82.5%). FINDINGS: The study findings
      showed that the majority of the respondents were based in both hospital and
      community, held paediatric qualifications and had undertaken further training to
      prepare as diabetes specialists. Respondents used a wide range of teaching
      methods and materials in the educational process. A substantial number of
      individuals and voluntary organizations were also involved in diabetes education.
      CONCLUSIONS: The findings of this study support the belief that the PDSN, as a
      member of the multidisciplinary paediatric diabetes team, has a key role in the
      education of children with diabetes and their parents/carers. However, the
      importance of the team approach as a whole should not be underestimated.

PMID- 11251717
TI  - Relatives of hospitalized stroke patients: their needs for information,
      counselling and accessibility.
AB  - AIM OF THE STUDY: The purpose of this study is to explore the needs of stroke
      patients' relatives during the hospitalization period. BACKGROUND: In the
      Netherlands, the consequences of a stroke, and the needs of stroke patients and
      their relatives are becoming increasingly important. In hospital, however,
      nursing care is still focused on the patients. A previous qualitative study on
      the needs of relatives of stroke patients identified four categories of needs.
      This present study aims to test the results of the previous study in a larger
      setting and to identify the factors that influence the needs of the relatives.
      DESIGN/METHODS: This study uses a cross-sectional design. A questionnaire was
      designed for the purpose of data collection. This questionnaire was completed by
      106 relatives of stroke patients admitted to the neurology wards of 19 Dutch
      hospitals (response rate 64%). The data were analysed using descriptive and
      multivariate analyses. RESULTS/FINDINGS: The findings of the study indicate that
      the needs of the relatives of stroke patients are best divided into three
      categories. These are the need for information, counselling (a combination of
      communication and support) and accessibility. In all cases, the most important
      need of the relatives of stroke patients is that their questions are answered
      honestly. The findings show a discrepancy between the importance of the needs and
      the degree to which these needs are met. Multivariate data analyses show that
      female relatives requested most information, whereas highly educated relatives
      needed less counselling. Satisfaction about the care provided is positively
      influenced by the period of hospitalization and negatively influenced by prior
      experiences of hospitalization.

PMID- 11251718
TI  - Impact of urinary and climacteric symptoms on social and sexual life after
      surgical treatment of stress urinary incontinence in women: a long-term outcome.
AB  - AIM: The aim of the present study was to evaluate the long-term results of
      surgical treatment of stress urinary incontinence (SUI) using both subjective and
      objective methods. BACKGROUND: Few studies have focused on the influence of
      biological and social changes in a woman's life on the long-term outcome of
      surgical treatment of stress urinary incontinence. METHODS: The study included 45
      women with genuine SUI treated with either retropubic urethrocystopexy (n=30) or
      puboccocygeal repair (n=15). The assessment included interviews, questionnaires,
      urinary diary, pad test, continence test and urodynamic investigation. RESULTS:
      The results were evaluated at intervals of 3 months, 1 year and 5--7 years after
      the treatment. One year after the surgical treatment 71% of the women in the
      urethrocystopexy group and 80% in the pubococcygeal repair group were
      subjectively cured, while 5--7 years after surgery the corresponding values were
      43% vs. 60%. However, according to pad test a 67% of the women in the
      urethrocystopexy group and 47% in the pubococcygeal repair group had ceased to
      leak urine 1 year after the operation whereas at the long-term follow-up the
      corresponding values were 64% vs. 71%. According to the questionnaire at the long
      term follow-up only 35% of the women in the whole group had genuine SUI whereas
      21% had urge-incontinence. Moreover, 37% experienced sweating, 23% flushing and
      44% vaginal dryness. The number of women with adiposity had increased
      significantly (P < 0.001) at the long-term follow-up. Twenty-eight per cent of
      the women decreased their activities whereas the majority experienced no
      impediment. Seventy-nine per cent reported that they were sexually active and the
      majority reported satisfaction with their sexual lives. CONCLUSIONS: Accurate
      assessment of postoperative results of SUI demands rigorous recording of
      subjective and objective data taking into consideration psychological and social
      factors, otherwise there is a high risk of bias in the interpretation of the
      results of the treatment for SUI. This study indicates that, in order to give
      women with SUI adequate treatment the nursing care should comprehend the women's
      divergent experiences of urinary incontinence and its impact on social and sexual
      life.

PMID- 11251719
TI  - A case study of nurse management of upper respiratory tract infections in general
      practice.
AB  - BACKGROUND: Nurses increasingly manage acute illness in United Kingdom (UK)
      general practice. Few data exist about patients routinely consulting with these
      nurses. There are concerns that providing this additional service will lower
      thresholds for consulting with an overall increase in workload. Upper respiratory
      tract infection (URTI) is the commonest reason for consulting. Inappropriate
      antibiotics promote resistant bacteria. Nurse management of URTI is an ideal
      opportunity to promote self-care and nonantibiotic management. AIMS: To describe
      the effects of a specially trained practice nurse managing URTI in a general
      practice in Cardiff, UK. METHODS: Descriptive study. RESULTS: Data were collected
      on 132 patients consulting with the nurse. We also collected data on 234 patients
      consulting general practitioners (GPs) in the same practice. Patients seen by the
      nurse were younger and less likely to be given antibiotics at the time of their
      index illness than those who saw GPs (7% vs. 93%; P < 0.001). During the year
      following the consultation with the nurse, patients consulted slightly less often
      and received antibiotics for URTI less often compared with the year preceding
      this consultation (P=0.02). Their consultation rate for all conditions did not
      change. The consultation rates for URTI of the patients managed by the GPs
      remained constant and consultations for all conditions increased (P < 0.01).
      CONCLUSIONS: Nurse management of URTI did not lower patients' threshold for
      future consulting, and patients who saw her were prescribed antibiotics less
      often.

PMID- 11251720
TI  - Male appropriation and medicalization of childbirth: an historical analysis.
AB  - AIMS OF THE PAPER: This paper aims to explore through historical analysis some of
      the means by which medicine successfully appropriated and medicalized pregnancy
      and childbirth and to consider the impact that this has had on women's
      experiences within maternity care. BACKGROUND AND RATIONALE: The appropriation
      and medicalization of pregnancy and childbirth by men are rooted in a patriarchal
      model that has been centuries in the making. A model that perceives women as
      essentially abnormal, as victims of their reproductive systems and hormones, it
      is also one that defines pregnancy as inherently pathological - a clinical crisis
      worthy of active intervention. In both law and medicine men have used their power
      to define reproduction as a biological defect (LeMoncheck L. 1996 Journal of
      Clinical Ethics 7, 160--176), requiring both legal regulation and medical
      intervention, whilst feminist writers have long argued that women's experiences
      within the health care system at least to some extent reflects their social
      position. CONCLUSIONS: Male justifications of female inferiority have been
      developed and nurtured through professional discourses and socialization
      processes inherent within medical education and practice (Cahill H. 1999 MA
      Thesis, University of Keele). These assumptions are internalized and reproduced
      to shape quite profoundly, the nature of doctors' interactions with women in
      their care. Perhaps more fundamentally, such discursive explanations of women's
      bodies as inherently defective continue to shape women's position in society.
      Maternity care is a key area in which women's ability to exercise real choice and
      make informed decisions is limited and where doctor-patient interactions are
      themselves constructions of existing gender orders; women's autonomy continues to
      be violated through both quite subtle and overt discourse and practice.

PMID- 11251721
TI  - Data collection with adolescents.
AB  - Adolescence spans a wide time period during which development and its context
      influence behaviour and the strategies used for data collection. This article
      addresses problems that can be anticipated in data collection with adolescents.
      Problems are presented that are associated with adolescent developmental
      capacities, adolescent developmental change and stability, gender and ethnicity.
      Some problems are specific to certain settings or to certain data collection
      methods. The application of theoretical and empirical knowledge about adolescent
      development can strengthen data collection instruments and procedures. Strategies
      to enhance data collection include carefully defining adolescence and tailoring
      procedures and protocols based on a theoretical understanding of the biological,
      cognitive and emotional development of adolescents in conjunction with an
      understanding of the characteristics of the research setting. Adolescent research
      settings can pose challenges. Investigators must understand clinic routines in
      evaluating the feasibility of implementing protocols and collecting data where
      there are distractions and time constraints. In education settings, strategies
      must be used to collect data in a group context where peer pressure can affect
      responses. In home settings, ingrained response patterns and family norms can
      also impede obtaining valid perspectives from adolescents. Ethnicity as well may
      play an important role that must be addressed when designing and implementing
      data collection with adolescents. Procedures and instruments selected to collect
      data need to address variations in ethnicity.

PMID- 11251722
TI  - Exploring caring using narrative methodology: an analysis of the approach.
AB  - The investigation of caring in nursing practice and the need to explicate what it
      is nurses do when they care present a challenge for nurse researchers. This is
      due largely to the complex and nebulous nature of caring as a concept and the
      contextual elements that influence its perceived meaning. Consequently, the use
      of qualitative methods in the exploration of caring is the method of choice, with
      researchers employing a variety of such approaches. In particular, the use of
      stories as a primary way of making sense of an experience has gained attention in
      the literature and the narrative method is being seen increasingly as a valid
      means of tapping into the patient experience. However, the use of narratives is
      complex with a diversity of approaches often being presented. This paper
      discusses the use of narratives in the exploration of caring, focusing
      specifically on an approach developed by Donald Polkinghorne. Issues associated
      with the collection and analysis of narrative data using this approach are
      examined.

PMID- 11251723
TI  - Harm reduction theories and strategies for control of human immunodeficiency
      virus: a review of the literature.
AB  - AIM: To provide a comprehensive review of the literature on harm reduction
      theories and strategies related primarily to licit and illicit drug use.
      BACKGROUND: Although human immunodeficiency virus (HIV)/acquired immunodeficiency
      syndrome (AIDS) disease transmission is well understood, it continues to spread,
      particularly among injection drug users (IDUs). Despite early indications that
      HIV would be contained within the IDU community, it is spreading to non-IDU
      sexual partners and to children of IDUs, threatening a more widespread epidemic.
      METHODS: An examination of research studies and theoretical writings including
      reviews and policy papers published in English between 1990 and 2000. RESULTS:
      Harm reduction does not seek to eliminate drug use; it focuses on minimizing the
      personal and social harms and costs associated with drug use and spread of HIV.
      It seeks to ameliorate conditions surrounding drug use responsible for the spread
      of HIV in the IDU community: unequal access to health services; sharing of
      infected needles; racial and social discrimination; poverty; exposure to street
      violence; inadequate housing; lack of employment; poor general or mental health
      and other demographic and social determinants. Some controversial harm reduction
      strategies are described: methadone maintenance programmes, illegal drugs
      dispensing under controlled conditions, needle exchanges, HIV testing, vein
      maintenance, safe-sex and would-care programmes. CONCLUSION: The main challenge
      is to get IDUs to protect themselves against HIV when suffering physical and
      social privations and addiction needs. Diverse perspectives on harm reduction are
      problematic with consequences for success of drug use initiatives. Practical,
      ethical and theoretical complexities exist but further research is needed to
      build support for a harm-reduction orientation in practice and policy
      formulation.

PMID- 11251724
TI  - 'More than just money' -- widening the understanding of the costs involved in
      cancer care.
AB  - AIM: This paper examines the literature relating to the wider concept of cost in
      cancer care and the implications this has for the development of services
      particularly within the changing context of cancer care. BACKGROUND: Cancer
      remains a major cause of morbidity and mortality in the United Kingdom (UK),
      treatment is often complex and expensive; both in financial and human terms.
      Service patterns for cancer care are shifting away from traditional inpatient,
      hospital settings towards short stay/day-care and home care models. This is in
      response to developments in health care policy, but it is also because of the
      availability of better tolerated treatments and demand for more patient-focused
      health care. REVIEW OF THE LITERATURE: The databases of Cinhahl and Medline were
      accessed using the keywords of costs, treatment, outpatients, home care and
      cancer. Additional sources of literature were also accessed through hand
      searching key journals. The paper explores the literature in three themes. First,
      the cost-effectiveness of cancer treatment; second, the often invisible indirect
      or 'out of pocket' costs incurred by patients and their families during cancer
      treatment and finally, the 'human costs' of a cancer diagnosis and cancer
      therapy. CONCLUSIONS: In view of recent calls to improve the effectiveness of
      cancer care in the UK, we suggest that research is needed to address all the
      dimensions of cost. It is only by exploring total costs from this broad
      perspective that appropriate, effective and holistic services can be planned for
      the future.

PMID- 11251725
TI  - Comparisons of the cost-effectiveness among hospital chronic care, nursing home
      placement, home nursing care and family care for severe stroke patients.
AB  - AIM: This study compared the cost and effectiveness of long-term institutional
      care and home care for stroke patients with severe physical disabilities.
      BACKGROUND: Whether home care is more economical or effective than institutional
      care for patients with chronic illnesses remains controversial when the cost of
      family labour is considered. Thus, decisions concerning the appropriate type of
      care setting for patients with severe chronic illness remain difficult. METHODS:
      From November 1995 to March 1996, 313 hospitalized stroke patients with severe
      physical disabilities treated at one of five hospitals in the Taipei metropolitan
      area were followed from the day of hospital discharge until the third month after
      discharge. These 313 patients were divided into four groups as follows: (1) 106
      who were admitted to a chronic care unit in a hospital, (2) 60 who were admitted
      to nursing homes, (3) 60 who received professional home nursing care and (4) 87
      who returned home without receiving professional care. The change of physical
      functional status in the patient was examined as the difference between
      activities of daily living (ADL) scores measured at discharge and at the end of
      the third month after discharge. RESULTS: Information on family costs for
      caregiving, including pay for long-term services utilized, labour costs for
      caregiving and out-of-pocket expenditures for miscellaneous materials was
      obtained during a weekly telephone interview. The results indicated that caring
      for patients in their own homes was not only more expensive but was also less
      effective in improving ADL scores than caring for patients in nursing homes and
      in chronic care units of hospitals. CONCLUSIONS: The results suggest that caring
      for patients with severe physical disabilities in institutions is more
      appropriate than caring of them at home.

PMID- 11251726
TI  - Nursing in the public sphere: health policy research in a changing world.
AB  - AIMS OF THE PAPER: To identify recent trends in the academic field of health
      policy, setting them in the context of wider changes in the socio-political and
      research environments and considering their implications for nursing research.
      BACKGROUND: Health policy is a well-established field of academic study and
      research in the United Kingdom (UK). The 1990s have seen some important
      intellectual developments in this field, as well as some major changes in the
      context of health-related research. DESIGN: A selective review of the relevant
      literature. CONCLUSIONS: The Department of Health's new Research & Development
      strategy can be understood as part of a wider trend, moving away from the
      traditional, university-based model of knowledge production towards a new one
      which involves other groups, such as employers, practitioners and patients. This
      may increase the opportunities for health care professionals in general - and
      nurses in particular - to influence the research agenda and to participate as
      researchers in the critical evaluation of health policy.

PMID- 11251727
TI  - Occupational stressors and coping as determinants of burnout in female hospice
      nurses.
AB  - AIMS: Stressors, coping and demographic variables were examined as predictors of
      burnout in a sample of hospice nurses. The study aimed to investigate the level
      of burnout among hospice nurses; to ascertain which aspects of nursing work were
      positively or negatively related to burnout; to examine the relative
      contributions made by these different variables and to suggest individual and
      organizational interventions to reduce levels of burnout. METHODS: Eighty-nine
      female nurses from nine hospices completed a battery of questionnaires comprising
      the Maslach Burnout Inventory, Nursing Stress Scale, Ways of Coping Scale and a
      demographic information form. RESULTS: In general, the level of burnout
      (characterized by high emotional exhaustion, high depersonalization of patients
      and low personal accomplishment) was found to be low. In multiple regression
      analyses, 'death and dying', "conflict with staff', 'accepting responsibility'
      and higher nursing grade contributed to emotional exhaustion. 'Conflict with
      staff', 'inadequate preparation', 'escape' and reduced 'planful problem-solving'
      contributed to depersonalization. 'Inadequate preparation', 'escape', reduced
      'positive reappraisal' and fewer professional qualifications contributed to lower
      levels of personal accomplishment. Overall, stressors made the greatest
      contribution to burnout and demographic factors contributed the least.
      CONCLUSIONS: The importance of not labelling individuals as good and bad 'copers'
      was discussed, as the effectiveness of a strategy may depend on the situation. It
      was concluded that the investigation of problem-focused and emotion-focused
      coping in relation to burnout, was oversimplifying the coping-burnout
      relationship. Suggestions for stress management included staff training in
      counselling skills, monitoring staff conflict, implementing stress inoculation
      training to teach appropriate use of coping skills and finally, monitoring
      particularly vulnerable groups of hospice staff such as unqualified nursing
      assistants and qualified nurses in management positions. It was concluded that
      despite the difficult nature of hospice work, the hospice is a positive
      environment in which to work.

PMID- 11251728
TI  - The nurse's workload in care situations.
AB  - AIM: The aim of this study was to describe the nurse's workload in care
      situations and on different work shifts on surgical and medical wards. Changes in
      heart rate, shoulder-neck muscle tension and perceived exertion were measured in
      these care situations. DESIGN: Nurses' physical fitness was tested using a
      clinical exercise test. RESULTS: Transportation of a patient to the operating
      theatre was the most strenuous care situation on morning and evening shifts.
      Primary care, and situations related to practical nursing procedures were the
      second most strenuous situations regardless of the shift. Workload in primary
      care situations and in transporting the patient can be classified as medium heavy
      based on heart rate and relative workload, whereas in other situations it can be
      classified on average as moderate or light. The nurse's good physical fitness was
      reflected in relative workload in care situations so that in primary care and
      practical nursing procedures there was a statistically significant difference
      between those who scored high on a fitness test and those who scored low.
      Transferring tasks and practical nursing procedures involved more shoulder-neck
      muscle tension than other care situations.

PMID- 11251729
TI  - Shifting meaning of asylum.
AB  - AIM(S): This paper offers an expanded way of looking at the idea of asylum from
      the perspective of Soja's conceptualization of Thirdspace (Blackwell Publishers,
      Oxford 1996). Implications for research are discussed. BACKGROUND: Soja proposes
      a different way to think about space. He writes not of dialectics but instead of
      trialectics which reconstructs space. Soja rejects the binarism of either/or
      logic about space suggesting a creative combination of both/and also. In this
      instance, the binary logic of either hospital or community asylum is opened to
      new possibilities of thinking about the space of asylum. CONCLUSIONS: The value
      of hearing the stories of those living with long-term mental illness is to obtain
      an emic perspective of their space of asylum.

PMID- 11251730
TI  - The validity of Antonovsky's Sense of Coherence measure in a sample of
      schizophrenic patients living in the community.
AB  - AIM OF THE STUDY: To examine the construct and predictive validity of
      Antonovsky's Sense of Coherence (SOC) concept in a sample of schizophrenic
      persons living in the community. BACKGROUND: The salutogenic model of Antonovsky
      proposes that the individual's sense of coherence, which is a personal
      orientation towards life, determines the health experience. The salutogenic
      perspective might in several advantageous aspects contribute to the care and
      support for patients with a long and persistent mental illness like
      schizophrenia. DESIGN: The study is a 18-month follow-up study. Structured
      interviews were used to interview 120 patients with a diagnosis of schizophrenia
      or a schizoaffective disorder. Pearlin's mastery scale, Rosenberg's self-esteem
      scale, the Interview Schedule for Social Interactions (ISSI) and the Brief
      Psychiatric Rating Scale (BPRS) were used as construct validity measures of the
      SOC scale. Health related measures such as quality of life, global well-being,
      satisfaction with health assessed by the Lancashire Quality of Life Profile
      (LQOLP) and global psychosocial functioning (GAF) were used in calculations of
      the predictive validity of SOC. RESULTS: The SOC was positively related to
      mastery, self-esteem and social support but negatively associated to
      psychopathology. In total, mastery, self-esteem and adequacy of social
      integration explained 61.1% of the variance in SOC, and mastery contributed with
      the greatest part of the variance, 46.3% SOC was positively associated to all
      health related measures and changes in SOC during an 18-month follow-up was
      positively correlated to changes in overall subjective quality of life, general
      health, global well-being and global psychosocial functioning. CONCLUSION: The
      results gave support to the construct and predictive validity of the SOC measure
      in individuals suffering from a diagnosis of schizophrenia.

PMID- 11251731
TI  - Biological correlates of Reiki Touch(sm) healing.
AB  - BACKGROUND: Despite the popularity of touch therapies, theoretical understanding
      of the mechanisms of effect is not well developed and there is limited research
      measuring biological outcomes. AIMS: The aim of this study was to test a
      framework of relaxation or stress reduction as a mechanism of touch therapy.
      METHODS: The study was conducted in 1996 and involved the examination of select
      physiological and biochemical effects and the experience of 30 minutes of Reiki,
      a form of touch therapy. A single group repeated measure design was used to study
      Reiki Touch'ssm effects with a convenience sample of 23 essentially healthy
      subjects. Biological markers related to stress-reduction response included state
      anxiety, salivary IgA and cortisol, blood pressure, galvanic skin response (GSR),
      muscle tension and skin temperature. Data were collected before, during and
      immediately after the session. RESULTS: Comparing before and after measures,
      anxiety was significantly reduced, t(22)=2.45, P=0.02. Salivary IgA levels rose
      significantly, t(19)=2.33, P=0.03, however, salivary cortisol was not
      statistically significant. There was a significant drop in systolic blood
      pressure (SBP), F(2, 44)=6.60, P < 0.01. Skin temperature increased and
      electromyograph (EMG) decreased during the treatment, but before and after
      differences were not significant. CONCLUSIONS: These findings suggest both
      biochemical and physiological changes in the direction of relaxation. The
      salivary IgA findings warrant further study to explore the effects of human TT
      and humeral immune function.

PMID- 11251733
TI  - Patients' and relatives' experiences and perspectives of 'Good' and 'Not so Good'
      quality care.
AB  - AIMS: To explore patients' and relatives' perceptions of care and identify key
      criteria used to evaluate quality care, via descriptions of actual care
      experiences. METHOD: A qualitative approach using Grounded Theory was adopted;
      data collected by semistructured interviews, from a purposive sample of 34 acute
      medical patients and 7 relatives, was subjected to question and thematic
      analysis. FINDINGS: The nature of the care provided and interpersonal aspects of
      caring emerged as key quality issues for patients. Good Quality Care was
      characterized as individualized, patient focused and related to need; it was
      provided humanistically, through the presence of a caring relationship by staff
      who demonstrated involvement, commitment and concern. Care described as 'Not so
      Good' was routine, unrelated to need and delivered in an impersonal manner, by
      distant staff who did not know or involve patients. CONCLUSIONS: Empirical
      evidence was found which support these findings, which are in opposition of the
      received view that patients place greater emphasis on the technical aspects of
      care tasks. The quality issues identified as important by patients and relatives
      in this study are not always evaluated in care audits. Those responsible for
      evaluating health care quality might consider combining traditional
      (professional/technical) audit criteria with those used by health care users to
      achieve a more comprehensive evaluation.

PMID- 11251732
TI  - A critical incident study of nurses' responses to the spiritual needs of their
      patients.
AB  - AIMS OF STUDY: The aims of the study were to carry out a critical incident study
      to: (1) Describe what nurses consider to be spiritual needs; (2) Explore how
      nurses respond to the spiritual needs of their patients; (3) Typify nurses'
      involvement in spiritual dimensions of care; (4) Describe the effect of nurses'
      intervention related to spiritual care. BACKGROUND: In the caring professions a
      focus on individuals as bio-psychological-spiritual beings is gaining recognition
      and this notion is based on the premise that there should be a balance of mind,
      body and spirit for the maintenance of health in a person (Stoll 1979). Emerging
      research highlights the importance of spiritual care in nursing and suggests that
      there is scope for improving this dimension of care in order to improve the
      quality of life for many patients. However, there is very little evidence about
      how nurses respond to the spiritual needs of their patients. Therefore the
      purpose of this study was to map by critical incident techniques how nurses
      construct and respond to patients' spiritual needs in a variety of clinical
      settings. METHODS: Critical incidents were obtained from 115 nurses. The data
      from these incidents were subjected to content analysis and categories were
      developed and described. The emerging categories were subjected to peer reviews
      to ensure reliability and validity of findings. FINDINGS: The findings suggest
      that there is confusion over the notion of spirituality and the nurse's role
      related to spiritual care. A variety of approaches to spiritual care emerged in
      this study from the critical incidents derived from nurse respondents. These were
      categorized as 'personal', 'procedural', 'culturalisit' or 'evangelical'. There
      was an overwhelming consensus that patients' faith and trust in nurses produces a
      positive effect on patients and families, and nurses themselves derived
      satisfaction from the experience of giving spiritual care. In this respect,
      spiritual care interventions promote a sense of well-being in nurses as well as
      being a valuable part of total patient care. CONCLUSION: The study concluded that
      there is scope for developing an ideal model of spiritual care using the critical
      incident data from this study.

PMID- 11251734
TI  - Nursing competencies: personal characteristics contributing to effective nursing
      performance.
AB  - AIMS OF THE STUDY: Core competencies are important in enabling an individual to
      adapt to new environments and perform superior professional practice. This study
      was to identify the underlying competencies which contributed to effective
      nursing performance. BACKGROUND: Most of the previous competencies are either
      derived from researchers' conceptual analysis or based on practitioners' direct
      report. Competencies derived from these methods either are subject to bias or are
      unable to identify the essential elements for effective nursing care. METHOD:
      Following the McBer method, 50 experienced nurses in China were asked to report
      82 valid critical incidents in their jobs. Two individuals coded the scripts and
      decided the presence of each competency according to a pre-established coding
      system. RESULTS: Ten competencies including interpersonal understanding,
      commitment, information gathering, etc. were identified. Each competency was
      illustrated by behavioural indicators. CONCLUSIONS: Skills, traits, motives and
      attitudes all contribute to effective nursing performance. The findings assist in
      the delineation and development of nursing competencies and thus provide
      realistic working behaviours for nursing education and management.

PMID- 11251735
TI  - Changing to primary nursing in a nursing home in Finland: experiences of
      residents, their family members and nurses.
AB  - AIM: The aim of the study was to find out how nursing home residents, their
      families and nurses experienced the change to primary nursing in the nursing
      home. BACKGROUND: This study was carried out in a nursing home in Finland.
      Following years of functional nursing, the change to primary nursing had started
      18 months prior to data collection. The transition was preceded by staff
      training, planning for the change to primary nursing and discussions with staff
      members. Meetings were also arranged with family members to inform them of what
      was happening and why. Staff implemented the changeover independently with the
      support of the institution's management. METHODS: The data were gathered in
      focused interviews. There were five interview themes: change in the nursing home,
      the position of the resident in the nursing home, the relationship between the
      resident and nurse, the relationship between family member and nurse, and the
      role of the nurse as provider of nursing care. FINDINGS: Residents reported no
      major changes in nursing care or in their relationship with nurses. However,
      family members had noticed changes in the behaviour of the nursing staff. Staff
      members had become friendlier, spent more time with the residents and showed a
      strong job motivation. Cooperation between nurses and family members had changed
      very little. Some nurses in the early stages of the change tended to show signs
      of resistance. Others said that there had been many changes during the past year,
      that they acted more independently and could use their own decision-making
      authority more freely than before. They treated residents as individuals and gave
      them a greater say in decision-making. They felt responsible for the development
      of the workplace as a collectivity. CONCLUSIONS: Primary nursing is one way in
      which nurses and family members can work more closely in the best interests of
      older residents. The findings of this study speak in favour of making the change
      from functional to primary nursing and at the same time highlight certain
      problems and possibilities in this process.

PMID- 11251736
TI  - How nurses manage time and work in long-term care.
AB  - AIMS OF THE STUDY: The aim of this study was to better understand the ways in
      which conditions of work, including staffing, affect how nurses in long-term care
      (LTC) facilities do their jobs and the quality of care they provide. BACKGROUND:
      The research reported here was performed in the context of public policy debates
      about the relationship between staffing levels and quality in LTC. METHODS: In
      1995 and 1996, interviews and participant observation were used to examine how 18
      licensed nurses employed in two LTC facilities in the midwestern United States
      experience their day-to-day work. RESULTS: Time was an extremely salient work
      condition for the nurses interviewed. Under conditions of too little time and
      many interruptions, nurses compensated by developing strategies to keep up or
      catch up. These strategies included minimizing the time spent doing required
      tasks, creating new time and redefining work responsibilities. Although these
      strategies allowed nurses to complete the tasks for which they were accountable,
      there were adverse consequences for nurses and residents. Nurses realized that
      time demands often made it impossible to provide care of high quality. They
      expressed their ideas about quality care as the notion of 'should do' work. In
      effect, time pressures forced them to forego the 'should do' work to complete the
      'must do' work. CONCLUSION: Increased staffing could improve the quality of care
      in LTC facilities.

PMID- 11251737
TI  - The effects of clinical supervision on the quality of care: examining the results
      of team supervision.
AB  - AIM(S) OF THE STUDY: This study is part of a larger research project (1995-1998)
      aiming at quality improvement by means of clinical supervision (CS). The purpose
      of the study is to ascertain the conceptions of five ward teams having CS of its
      effects on the quality of care. BACKGROUND: The quality of nursing care has been
      debated since at least the 1980s. An extensive literature and research reports
      describe a variety of interventions and methods to improve the quality of care.
      One of the interventions is CS. However, the amount of empirical research
      exploring the effects of CS especially on the quality of care is limited. METHOD:
      Data were collected using group interviews and analysed using the method of
      phenomenography. FINDINGS: The following categories describing the conceptions
      related to CS and to the quality of care emerged: knowledge, change and 'I and we
      as providers of quality'. Conceptions of the effects varied between and within
      the teams and sometimes contradicted each other. The importance of knowledge was
      underlined on three of the five wards. The patient's point of view emerged only
      on one ward. CONCLUSIONS: It can be concluded that CS has effects on the quality
      of care and it can be considered a quality improving intervention in nursing
      practice. However, the knowledge of the different conceptions produced in this
      study also gives proof that team supervision is a challenge for supervisors.

PMID- 11251738
TI  - Teacher candidates' reflective teaching and learning in a hospital setting -
      changing the pattern of practical training: a challenge to growing into
      teacherhood.
AB  - AIMS OF THE PROJECT: The main goal of the 'teacher candidates' reflective
      teaching and learning' project was to integrate theories of reflection in
      education and nursing practice. This was realised through teacher candidates'
      practical training in a hospital setting providing them with personal experiences
      of reflection in different forms and contexts. In this paper one teacher
      candidate pair's experiences of developing documentation in one operating theatre
      are described. BACKGROUND: The power of reflection is acknowledged in health care
      education and, on the other hand, also in nursing practice. Reflection, however,
      is not spontaneous but it requires active contribution. The key persons in this
      respect seem to be healthcare teachers. The challenges for today are that, for
      example, the theoretical background of reflection is multi-fold and that the
      concept of reflection is popularised in common use. DESIGN OF THE PROJECT: The
      project (1995-1998) was accomplished in one of the biggest university hospitals
      in Finland. On the collaborating wards, systematic team supervision was in
      progress. Teacher candidates planned and implemented in-service-training modules
      for teams based on educational needs raised during team supervision sessions.
      FINDINGS: The contribution of the project can be assessed as important to health
      care teacher education, but also to nursing practice. Practical training in a
      hospital setting enhanced teacher candidates' ability to work as teachers in a
      hospital organisation as well as a nursing college/polytechnic by providing them
      with a new viewpoint. They learned valuable lessons from applying theory, as
      planning in-service-training required continuous reflective discussion with the
      nursing staff but also theoretical reflection. Improvements in nursing practice
      were also promoted as staff educational needs were met. CONCLUSIONS: Shifting the
      teacher candidates' practical training into a hospital setting and emphasising
      reflection seemed to promote their professional development towards teacherhood
      and improve nursing practice.

PMID- 11251739
TI  - Bridging theory and practice in the supervisory relationship: a sociocultural
      perspective.
AB  - AIM OF THE PAPER: This paper proposes alternative theoretical frameworks for
      conceptualizing supervisory relationships in clinical settings where professional
      development is the key activity. In discussing findings from the research,
      paradigm examples of students' mentor experiences will be used to illustrate
      socio-cultural theories of learning and their relevance to professional education
      in clinical settings. BACKGROUND RATIONALE: The concept of a theory-practice gap
      dominates approaches to preparing professionals for their future role. With
      increasing emphasis on work-based learning one of the many strategies designed to
      support students and professionals is supervision. This strategy has had mixed
      success. In many instances this is because of insufficient numbers of suitably
      experienced and prepared staff. Another factor is how supervision has been
      conceptualized. In professional education the term mentorship is often used
      synonymously with preceptorship and supervision. These terms are all concerned
      with activities intended to foster professional and educational development, and
      in many instances the learner is a novice working in an unfamiliar setting over a
      predefined period of time. RESEARCH AIMS AND DESIGN: This longitudinal study
      using a Constructivist/Naturalistic paradigm was designed to investigate factors
      influencing the professional development eight preregistration nursing students'
      during their practice experiences. A multimethod approach to data collection was
      used. An extensive literature review of nurse education texts was conducted.
      Research findings. The most significant influence was found to be effective
      mentorship. Characteristics of successful mentorship are best explained using
      frameworks derived from socio-cultural theories. Concepts of sponsorship,
      legitimate peripheral participation, scaffolding and zone of proximal development
      (ZPD) offer a more effective means to understand and implement an educational
      partnership for work-place learning.

PMID- 11251740
TI  - The questioning skills of clinical teachers and preceptors: a comparative study.
AB  - AIM OF THE STUDY: The purpose of this study, conducted as partial requirement for
      a Master of Nursing Studies Degree, was to explore, describe and compare the
      level of questions asked by clinical teachers and preceptors. BACKGROUND:
      Questioning is one of many teaching/learning strategies thought to facilitate the
      development of critical thinking skills which are integral to nursing practice.
      As such the type and number of questions asked have implications for student
      learning. Currently in Melbourne, Australia, many undergraduate nursing degree
      courses utilize both clinical teachers and preceptors to facilitate student
      learning in the clinical setting. DESIGN: A comparative descriptive design was
      used. Participants were given three acute care patient scenarios involving an
      undergraduate nursing student, as part of a questionnaire, and asked to identify
      the questions they would ask the student in relation to the scenario. FINDINGS:
      Data revealed that the clinical teachers had considerably more years of
      experience in their role and higher academic qualifications than did the
      preceptors. The clinical teachers also asked a greater number of questions
      overall and more from the higher cognitive level. Despite this, the findings
      suggest that both clinical teachers and especially preceptors need to increase
      the number of higher level questions they ask. CONCLUSIONS: Based on the findings
      of this study, it is evident that there is a need for further comparative studies
      into the questioning skills of clinical teachers and preceptors. Also, these two
      groups require education about the importance of higher level questioning for
      student learning as well as how to ask questions generally.

PMID- 11251741
TI  - The meaning of preceptorship: nurses' lived experience of being a preceptor.
AB  - AIM OF THE STUDY: This phenomenological study is aimed at illuminating nurses'
      lived experience of the process of preceptoring and the meaning of preceptorship
      in a Swedish context. METHODS: Seventeen nurses from the North of Sweden with
      varied previous experience of preceptorship volunteered to participate. Their
      narratives, describing their experience of being a personal preceptor for a
      student nurse during practical training on a hospital ward in the third year of a
      3-year diploma programme within a university college of nursing in Sweden, were
      transcribed verbatim. A phenomenological-hermeneutic interpretation disclosed the
      themes 'sheltering the students when learning' and 'facilitating the students'
      learning', together with eight sub-themes, which created an understanding of the
      meaning of preceptorship. FINDINGS AND DISCUSSION: The meaning of preceptorship
      was understood as reducing the risk of the students learning helplessness and
      empowering the students when learning in practice. The meaning of preceptorship
      highlighted the need for further preceptor support and development of the role of
      the preceptor. On the basis of the findings, suggestions were made to increase
      the preceptors' awareness of values in nursing practice and use of pedagogical
      strategies in the process of preceptoring. Through such strategies a reciprocal
      development of the preceptors' and the faculty's knowledge may take place, to the
      best advantage of the students' learning and the development of the profession.

PMID- 11251742
TI  - Symbolic interactionism as a theoretical perspective for multiple method
      research.
AB  - RATIONALE: Qualitative and quantitative research rely on different
      epistemological assumptions about the nature of knowledge. However, the majority
      of nurse researchers who use multiple method designs do not address the problem
      of differing theoretical perspectives. Traditionally, symbolic interactionism has
      been viewed as one perspective underpinning qualitative research, but it is also
      the basis for quantitative studies. Rooted in social psychology, symbolic
      interactionism has a rich intellectual heritage that spans more than a century.
      Underlying symbolic interactionism is the major assumption that individuals act
      on the basis of the meaning that things have for them. AIM: The purpose of this
      paper is to present symbolic interactionism as a theoretical perspective for
      multiple method designs with the aim of expanding the dialogue about new
      methodologies. CONCLUSION: Symbolic interactionism can serve as a theoretical
      perspective for conceptually clear and soundly implemented multiple method
      research that will expand the understanding of human health behaviour.

PMID- 11251743
TI  - Validation of a questionnaire to evaluate the quality of life of nonprofessional
      caregivers of dependent persons.
AB  - AIM OF THE STUDY: To determine the acceptance, validity and reliability of the
      questionnaire for assessing the type of informal care that caregivers of
      dependent people give and the effects this care might have on the health of the
      carer. BACKGROUND: In Spain, the formal health care system provides 12% of the
      total time dedicated to health care, the remaining 88% is carried out by the
      informal system within the home environment. The act of caring has effects on
      various areas of the life of the carer and on family functioning. This makes
      clear the existing risk when the principal carer becomes a secondary nurse.
      METHODS: This research was a cross-sectional design, carried out in
      municipalities in the province of Barcelona (Spain) from January to December
      1997. The subjects of the study were 240 caregivers of dependent people. The
      questionnaire (ICUB97Copyright ) is based on the Virginia Henderson's 14 Needs
      nursing model. The validity of the content was assessed through the consensus of
      a group of experts, validity of design by means of comparison with the
      hypotheses. RESULTS: Test-retest reliability was completed for the three parts of
      the questionnaire and the kappa index values was 0.89, 0.80 and 0.75 for each
      part. The higher the level of dependency of the person cared for, the more care
      tasks the carer had to perform. A correlation coefficient of 0.58 was obtained
      for the Barthel Index (P < 0.001) and 0.53 on the Philadelphia Index (P < 0.001).
      The care tasks performed by the carer showing greatest correlation with
      dependency level were; help with elimination (r=0.73, P < 0.001), help with
      feeding (r=0.55, P < 0.001) and help in personal development (r=0.55, P=0.001).
      CONCLUSIONS: This questionnaire provides a reliable and valid instrument for
      measuring the care given by caregivers to dependent people, to meet their basic
      needs as well as for assessing the needs of the carers who experience problems by
      the act of caring. It is therefore important for nursing practice, to have a
      validated instrument available for identifying the tasks performed by family
      carers and the effects on their health.

PMID- 11251744
TI  - Association of resident coverage with cost, length of stay, and profitability at
      a community hospital.
AB  - OBJECTIVE: The effect of care by medical residents on hospital length of stay
      (LOS), indirect costs, and reimbursement was last examined across a range of
      illnesses in 1981; the issue has never been examined at a community hospital. We
      studied resource utilization and reimbursement at a community hospital in
      relation to the involvement of medical residents. DESIGN: This nonrandomized
      observational study compared patients discharged from a general medicine teaching
      unit with those discharged from nonteaching general medical/surgical units.
      SETTING: A 620-bed community teaching hospital with a general medicine teaching
      unit (resident care) and several general medicine nonteaching units (no resident
      care). PATIENTS: All medical discharges between July 1998 and February 1999,
      excluding those from designated subspecialty and critical care units.
      MEASUREMENTS AND MAIN RESULTS: Endpoints included mean LOS in excess of expected
      LOS, mean cost in excess of expected mean payments, and mean profitability
      (payments minus total costs). Observed values were obtained from the hospital's
      database and expected values from a proprietary risk-cost adjustment program. No
      significant difference in LOS between 917 teaching-unit patients and 697
      nonteaching patients was demonstrated. Costs averaged $3,178 (95% confidence
      interval (CI) +/- $489) less than expected among teaching-unit patients and
      $4,153 (95% CI +/- $422) less than expected among nonteaching-unit patients.
      Payments were significantly higher per patient on the teaching unit than on the
      nonteaching units, and as a result mean, profitability was higher: $848 (95% CI
      +/- $307) per hospitalization for teaching-unit patients and $451 (95% CI +/-
      $327) for patients on the nonteaching units. Teaching-unit patients of attendings
      who rarely admitted to the teaching unit (nonteaching attendings) generated an
      average profit of $1,299 (95% CI +/- $613), while nonteaching patients of
      nonteaching attendings generated an average profit of $208 (95% CI +/- $437).
      CONCLUSIONS: Resident care at our community teaching hospital was associated with
      significantly higher costs but also with higher payments and greater
      profitability.

PMID- 11251745
TI  - A study of primary care teaching comparing academic and community-based settings.
AB  - OBJECTIVE: To compare teaching activity and content between academic and
      community-based practices used in third year medical student primary care
      training. SETTING: Academic and community-based primary care practices
      participating in third-year internal medicine, family medicine, and primary care
      core clerkships. PARTICIPANTS: Five-hundred thirteen preceptor-student encounters
      involving 32 preceptors and 26 third-year medical students were evaluated.
      DESIGN: Student-preceptor pairs collected a convenience sample of data from
      shared patient encounters. Preceptors recorded the content of teaching
      interventions, and students independently documented learning points received for
      each clinical encounter. MEASUREMENTS AND MAIN RESULTS: Comparison of problem
      exposure, frequency and content of teaching interventions, and the effect of
      patient complexity and patient care workload on teaching frequency was made
      between the academic and community-based practices. Several small differences
      were found in the frequency of clinical problem exposure between the 2 settings.
      The frequency and focus of teaching interventions did not differ by practice
      type. Teaching by community-based preceptors tended to decrease with increased
      patient care workload, but increased in academically based practices.
      CONCLUSIONS: Although several differences exist between educational experiences
      in community- and academically based primary care practices, they appear to be
      minor and of minimal educational significance.

PMID- 11251746
TI  - Finding cancer in primary care outpatients with low back pain: a comparison of
      diagnostic strategies.
AB  - OBJECTIVE: To compare strategies for diagnosing cancer in primary care patients
      with low back pain. Strategies differed in their use of clinical findings,
      erythrocyte sedimentation rate (ESR), and plain x-rays prior to imaging and
      biopsy. DESIGN: Decision analysis and cost effectiveness analysis with
      sensitivity analyses. Strategies were compared in terms of sensitivity,
      specificity, and diagnostic cost effectiveness ratios. SETTING: Hypothetical
      MEASUREMENTS: Estimates of disease prevalence and test characteristics were taken
      from the literature. Costs were represented by the Medicare reimbursement for the
      tests and procedures employed. MAIN RESULTS: In the baseline analysis, using
      magnetic resonance imaging (MRI) as the imaging procedure prior to a single
      biopsy, strategies ranged in sensitivity from 0.40 to 0.73, with corresponding
      diagnostic costs of $14 to $241 per patient and average cost effectiveness ratios
      of $5,283 to $49,814 per case of cancer found. Incremental cost effectiveness
      ratios varied from $8,397 to $624,781; 5 strategies were dominant in the baseline
      analysis. Use of a higher ESR cutoff point (50 mm/hr) improved specificity and
      cost effectiveness for certain strategies. Imaging with MRI, or bone scan
      followed in series by MRI, resulted in a fewer unnecessary biopsies than imaging
      with bone scan alone. Cancer prevalence was an important determinant of cost
      effectiveness. CONCLUSIONS: We recommend a strategy of imaging patients who have
      a clinical finding (history of cancer, age > or = 50 years, weight loss, or
      failure to improve with conservative therapy) in combination with either an
      elevated ESR (> 50 mm/hr) or a positive x-ray, or using the same approach but
      imaging directly those patients with a history of cancer.

PMID- 11251747
TI  - Comorbid clinical conditions in chronic fatigue: a co-twin control study.
AB  - OBJECTIVES: Chronically fatiguing illness, defined as fatigue for at least 6
      months, has been associated with various physical health conditions. Our
      objective was to determine whether there is a significant relationship between
      chronically fatiguing illness and 10 clinical conditions that frequently appear
      to be associated with fatigue, adjusting for the potentially confounding effects
      of psychiatric illness. DESIGN: A co-twin control study controlling for genetic
      and many environmental factors by comparing chronically fatigued twins with their
      nonfatigued co-twins. SETTING: A nationally distributed volunteer twin registry.
      PARTICIPANTS: The study included 127 twin pairs in which one member of the pair
      experienced fatigue of at least 6 months' duration and the co-twin was healthy
      and denied chronic fatigue. Fatigued twins were classified into 3 levels using
      increasingly stringent diagnostic criteria. MEASUREMENTS AND MAIN RESULTS: Twins
      reported on a history of fibromyalgia, irritable bowel syndrome, multiple
      chemical sensitivities, temporomandibular disorder, interstitial cystitis,
      postconcussion syndrome, tension headache, chronic low back pain, chronic pelvic
      pain (women), and chronic nonbacterial prostatitis (men). The prevalence of these
      comorbid clinical conditions was significantly higher in the fatigued twins
      compared to their nonfatigued co-twins. Most notably, compared to their
      nonfatigued co-twins, the chronically fatigued twins had higher rates of
      fibromyalgia (> 70% vs < 10%) and irritable bowel syndrome (> 50% vs < 5%). The
      strongest associations were observed between chronic fatigue and fibromyalgia
      (odds ratios > 20), irritable bowel syndrome, chronic pelvic pain, multiple
      chemical sensitivities, and temporomandibular disorder (all with odds ratios > or
      = 4). Regression analysis suggested that the number of comorbid clinical
      conditions associated with chronic fatigue could not be attributed solely to
      psychiatric illness. CONCLUSIONS: Chronically fatiguing illnesses were associated
      with high rates of many other clinical conditions. Thus, patients with chronic
      fatigue may present a complex clinical picture that poses diagnostic and
      management challenges. Nonetheless, clinicians should assess such patients for
      the presence of comorbid clinical conditions. Future research should provide a
      better understanding of the temporal relationship of the onset of fatigue and
      these conditions, and develop strategies for early intervention.

PMID- 11251748
TI  - The effect of discussions about advance directives on patients' satisfaction with
      primary care.
AB  - BACKGROUND: Discussions of end-of-life care should be held prior to acute,
      disabling events. Many barriers to having such discussions during primary care
      exist. These barriers include time constraints, communication difficulties, and
      perhaps physicians' anxiety that patients might react negatively to such
      discussions. OBJECTIVE: To assess the impact of discussions of advance directives
      on patients' satisfaction with their primary care physicians and outpatient
      visits. DESIGN: Prospective cohort study of patients enrolled in a randomized,
      controlled trial of the use of computers to remind primary care physicians to
      discuss advance directives with their elderly, chronically ill patients. SETTING:
      Academic primary care general internal medicine practice affiliated with an urban
      teaching hospital. PARTICIPANTS: Six hundred eighty-six patients who were at
      least 75 years old, or at least 50 years old with serious underlying disease, and
      their 87 primary care physicians (57 residents, 30 faculty general internists)
      participated in the study. MEASUREMENTS AND MAIN RESULTS: We assessed patients'
      satisfaction with their primary care physicians and visits via interviews held in
      the waiting room after completed visits. Controlling for satisfaction at
      enrollment and physician, patient, and visit factors, discussing advance
      directives was associated with greater satisfaction with the physician (P =.052).
      At follow-up, the strongest predictor of satisfaction with the primary care visit
      was having previously discussed advance directives with that physician (P =.004),
      with a trend towards greater visit satisfaction when discussions were held during
      that visit (P =.069). The percentage of patients scoring a visit as "excellent"
      increased from 34% for visits without prior advance directive discussions to 51%
      for visits with such discussions (P =.003). CONCLUSIONS: Elderly patients with
      chronic illnesses were more satisfied with their primary care physicians and
      outpatient visits when advanced directives were discussed. The improvement in
      visit satisfaction was substantial and persistent. This should encourage
      physicians to initiate such discussions to overcome communication barriers might
      result in reduced patient satisfaction levels.

PMID- 11251749
TI  - Understanding physicians' skills at providing end-of-life care perspectives of
      patients, families, and health care workers.
AB  - BACKGROUND: A framework for understanding and evaluating physicians' skills at
      providing end of life care from the perspectives of patients, families, and
      health care workers will promote better quality of care at the end of life.
      OBJECTIVE: To develop a comprehensive understanding of the factors contributing
      to the quality of physicians' care for dying patients. DESIGN: Qualitative study
      using focus groups and content analysis based on grounded theory. SETTING:
      Seattle, Washington. PARTICIPANTS: Eleven focus groups of patients with chronic
      obstructive pulmonary disease, AIDS, or cancer (79 patients); 3 groups of family
      members who had a loved one die of chronic disease (20 family members); 4 groups
      of nurses and social workers from hospice or acute care settings (27 health care
      workers); and 2 groups of physicians with expertise in end-of-life care (11
      physicians). RESULTS: We identified 12 domains of physicians' skills at providing
      end-of-life care: accessibility and continuity; team coordination and
      communication; communication with patients; patient education; inclusion and
      recognition of the family; competence; pain and symptom management; emotional
      support, personalization; attention to patient values; respect and humility; and
      support of patient decision making. within these domains, we identified 55
      specific components of physicians' skills. Domains identified most frequently by
      patients and families were emotional support and communication with patients.
      Patients with the 3 disease groups, families, and health care workers identified
      all 12 domains. Investigators used transcript analyses to construct a conceptual
      model of physicians' skills at providing end-of-life care that grouped domains
      into 5 categories. CONCLUSIONS: The 12 domains encompass the major aspects of
      physicians' skills at providing high-quality end-of-life care from the
      perspectives of patients, their families, and health care workers, and provide a
      new framework for understanding, evaluating, and teaching these skills. Our
      findings should focus physicians, physician-educators, and researchers on
      communication, emotional support, and accessibility to improve the quality of end
      of-life care.

PMID- 11251750
TI  - Can Internet-based continuing medical education improve physicians' skin cancer
      knowledge and skills?
AB  - We sought to determine whether an Internet-based continuing medical education
      (CME) program could improve physician confidence, knowledge, and clinical skills
      in managing pigmented skin lesions. The CME program provided an interactive,
      customized learning experience and incorporated well-established guidelines for
      recognizing malignant melanoma. During a 6-week evaluation period, 354 physicians
      completed the on-line program as well as a pretest and an identical posttest. Use
      of the CME program was associated with significant improvements in physician
      confidence, correct answers to a 10-question knowledge test (52% vs 85% correct),
      and correct answers to a 15-question clinical skills test (81% vs 90% correct).
      We found that the overall improvement in clinical skills was due to a marked
      increase in specificity and a small decrease in sensitivity for evaluating
      pigmented lesions. User satisfaction was extremely high. This popular and easily
      distributed online CME program increased physicians' confidence and knowledge of
      skin cancer. Remaining challenges include improving the program to increase
      physician sensitivity for evaluating pigmented lesions while preserving the
      enhanced specificity.

PMID- 11251751
TI  - Persistence of impaired functioning and psychological distress after medical
      hospitalization for men with co-occurring psychiatric and substance use
      disorders.
AB  - OBJECTIVE: To measure the persistence of impaired health-related quality of life
      (HRQL) and psychological distress associated with co-occurring psychiatric and
      substance use disorders in a longitudinal sample of medically hospitalized male
      veterans. DESIGN: A random sample followed observationally for 1 year after study
      enrollment. SETTING: Inpatient medical and surgical wards at 3 university
      affiliated Department of Veterans Affairs Medical Centers. PATIENTS/PARTICIPANTS:
      A random sample of 1,007 admissions to medical and surgical inpatient services,
      excluding women and admissions for psychiatric reasons. A subset of participants
      (n = 736) was designated for longitudinal follow-up assessments at 3 and 12
      months after study enrollment. This subset was selected to include all possible
      participants with study-administered psychiatric diagnoses (52%) frequency
      matched by date of study enrollment to approximately equivalent numbers of
      participants without psychiatric diagnoses (48%). MEASUREMENTS AND MAIN RESULTS:
      All participants were administered a computerized structured psychiatric
      diagnostic interview for 13 psychiatric (include substance use) disorders and
      received longitudinal assessments at 3 and 12months on a multidimensional measure
      of HRQL, the SF-36, and a measure of psychological distress, the Symptom
      Checklist, 90-item version. On average, HRQL declined and psychological distress
      increased over time (P <.05). Psychiatric disorders were associated with
      significantly greater impairments in functioning and increased distress on all
      measures (P <.001) except physical functioning (P <.05). These results were
      replicated in the patients (n = 130) who received inpatient or outpatient mental
      health or substance abuse services. CONCLUSIONS: General medical physicians need
      to evaluate the mental health status of their hospitalized and seriously ill
      patients. Effective mental health interventions can be initiated
      posthospitalization, either immediately in primary care or through referral to
      appropriate specialty care, and should improve health functioning over time.

PMID- 11251752
TI  - The need for data not dogma on the costs of graduate medical education.

PMID- 11251753
TI  - Out of darkness: shedding light on end-of-life care.

PMID- 11251754
TI  - A call for papers. Substance abuse: innovations in primary care.

PMID- 11251755
TI  - Reliable, valid, and educational in-training medical student evaluation
      overlooked.

PMID- 11251757
TI  - Reducing medication regimen complexity: a controlled trial.
AB  - OBJECTIVE: To determine if a visual intervention (medication grid) delivered to
      physicians can reduce medication regimen complexity. DESIGN: Nonrandomized,
      controlled trial. SETTING: Veterans Affairs medical center.
      PATIENTS/PARTICIPANTS: Eight hundred thirty-six patients taking at least 5
      medications at the time of admission and the 48 teams of physicians and students
      on the general medicine inpatient service. INTERVENTION: For intervention
      patients, a medication grid was created that displayed all of the patients'
      medicines and the times of administration for 1 week. This grid was delivered to
      the admitting resident soon after admission. MEASUREMENTS AND MAIN RESULTS: For
      the patients of each team of physicians, we calculated the change in the average
      number of medications and doses from admission to discharge. The number of
      medications in the intervention group decreased by 0.92 per patient, and
      increased by 1.65 in the control group (P <.001). The mean number of doses per
      day in the intervention group decreased by 2.47 per patient and increased by 3.83
      in the control group (P <.001). CONCLUSIONS: This simple intervention had a
      significant impact on medication regimen complexity in this population.
      Apparently, physicians were able to address polypharmacy when the issue was
      brought to their attention.

PMID- 11251758
TI  - Problem drinking and medication adherence among persons with HIV infection.
AB  - OBJECTIVE: To examine the relation between problem drinking and medication
      adherence among persons with HIV infection. DESIGN: Cross-sectional survey.
      SETTING/PARTICIPANTS: Two hundred twelve persons with HIV infection who visited 2
      outpatient clinics between December 1997 and February 1998. MEASUREMENTS AND MAIN
      RESULTS: Nineteen percent of subjects reported problem drinking during the
      previous month, 14% missed at least 1 dose of medication within the previous 24
      hours, and 30% did not take their medications as scheduled during the previous
      week. Problem drinkers were slightly more likely to report a missed dose (17% vs
      12 %, P =.38) and significantly more likely to report taking medicines off
      schedule (45% vs 26%, P =.02). Among drinking subtypes, taking medications off
      schedule was significantly associated with both heavy drinking (high
      quantity/frequency) (adjusted odds ratio [OR], 4.70; 95% confidence interval [95%
      CI], 1.49 to 14.84; P <.05) and hazardous drinking (adjusted OR, 2.64; 95% CI,
      1.07 to 6.53; P <.05). Problem drinkers were more likely to report missing
      medications because of forgetting (48% vs 35%, P =.10), running out of
      medications (15% vs 8%, P =.16), and consuming alcohol or drugs (26 % vs 3 %, P
      <.001). CONCLUSION: Problem drinking is associated with decreased medication
      adherence, particularly with taking medications off schedule during the previous
      week. Clinicians should assess for alcohol problems, link alcohol use severity to
      potential adherence problems, and monitor outcomes in both alcohol consumption
      and medication adherence.

PMID- 11251759
TI  - Health information in material safety data sheets for a chemical which causes
      asthma.
AB  - OBJECTIVE: To assess the quality of health information on material safety data
      sheets (MSDS) for a workplace chemical that is well known to cause or exacerbate
      asthma (toluene diisocyanate, TDI). DESIGN: We reviewed a random sample of 61
      MSDSs for TDI products produced by 30 manufacturers. MEASUREMENTS AND MAIN
      RESULTS: Two physicians independently abstracted data from each MSDS onto a
      standardized audit form. One manufacturer provided no language about any
      respiratory effects of TDI exposure. Asthma was listed as a potential health
      effect by only 15 of the 30 manufacturers (50%). Listing asthma in the MSDS was
      associated with higher toluene diisocyanate concentrations in the product (P
      <.042). Allergic or sensitizing respiratory reactions were listed by 21
      manufacturers (70%). CONCLUSIONS: Many MSDSs for toluene diisocyanate do not
      communicate clearly that exposure can cause or exacerbate asthma. This suggests
      that physicians should not rely on the MSDS for information about health effects
      of this chemical.

PMID- 11251760
TI  - A web exercise in evidence-based medicine using cognitive theory.
AB  - Our aim was to improve clinical reasoning skills by applying an established
      theory of memory, cognition, and decision making (fuzzy-trace theory) to
      instruction in evidence-based medicine. Decision-making tasks concerning chest
      pain evaluation in women were developed for medical students and internal
      medicine residents. The fuzzy-trace theory guided the selection of online sources
      (e.g., target articles) and decision-making tasks. Twelve students and 22
      internal medicine residents attended didactic conferences emphasizing search,
      evaluation, and clinical application of relevant evidence. A 17-item Likert scale
      questionnaire assessed participants' evaluation of the instruction. Ratings for
      each of the 17 items differed significantly from chance in favor of this
      alternative approach to instruction. We concluded that fuzzy-trace theory may be
      a useful guide for developing learning exercises in evidence-based medicine.

PMID- 11251761
TI  - Shared expectations for protection of identifiable health care information:
      report of a national consensus process.
AB  - OBJECTIVE: The Ethical Force Program is a collaborative effort to create
      performance measures for ethics in health care. This report lays out areas of
      consensus that may be amenable to performance measurement on protecting the
      privacy, confidentiality and security of identifiable health information. DESIGN:
      Iterative consensus development process. PARTICIPANTS: The program's oversight
      body and its expert panel on privacy include national leaders representing the
      perspectives of physicians, patients, purchasers, health plans, hospitals, and
      medical ethicists as well as public health, law, and medical informatics experts.
      METHODS AND MAIN RESULTS: The oversight body appointed a national Expert Advisory
      Panel on Privacy and Confidentiality in September 1998. This group compiled and
      reviewed existing norms, including governmental reports and legal standards,
      professional association policies, private organization statements and policies,
      accreditation standards, and ethical opinions. A set of specific and assessable
      expectations for ethical conduct in this domain was then drafted and refined
      through 7 meetings over 16 months. In the final 2 iterations, each expectation
      was graded on a scale of 1 to 10 by each oversight body member on whether it was:
      (1) important, (2) universally applicable, (3) feasible to measure, and (4)
      realistic to implement. The expectations that did not score more than 7 (mean) on
      all 4 scales were reconsidered and retained only if the entire oversight body
      agreed that they should be used as potential subjects for performance
      measurement. Consensus was achieved on 34 specific expectations. The expectations
      fell into 8 content areas, addressing the need for transparency of policies and
      practices, consent for use and disclosure of identifiable information,
      limitations on information that can be collected and by whom, individual access
      to one's own health records, security requirements for storage and transfer of
      information, provisions to ensure ongoing data quality, limitations on how
      identifiable information may be used, and provisions for meaningful
      accountability. CONCLUSIONS: This process established consensus on 34 measurable
      ethical expectations for the protection of privacy and confidentiality in health
      care. These expectations should apply to any organization with access to
      personally identifiable health information, including managed care organizations,
      physician groups, hospitals, other provider organizations, and purchasers.
      Performance measurement on these expectations may improve accountability across
      the health care system.

PMID- 11251763
TI  - Physician views on caring for hospitalized patients and the hospitalist model of
      inpatient care.
AB  - We surveyed 241 board-certified internists affiliated with a large teaching
      hospital (Boston, Mass) before implementing a hospitalist service to determine
      attitudes towards providing inpatient care and the hospitalist model. Of
      physicians surveyed, 66% responded. Most disagreed that inpatient care is "an
      inefficient use of my time," only 10% felt a hospitalist service would improve
      patient satisfaction, and 54% felt it would hurt patient-doctor relationships.
      Multivariable analyses suggest that physicians physically furthest from their
      inpatient site were had more favorable attitudes toward the hospitalist model;
      more experienced and busier physicians were more negative. Future investigations
      should determine strategies for implementing the hospitalist model which address
      physicians' concerns.

PMID- 11251762
TI  - Medication lists for elderly patients: clinic-derived versus in-home inspection
      and interview.
AB  - OBJECTIVE: To determine how often the lists of regular medications derived in
      geriatric clinics by examination of "medication bags" and interview matched those
      found during in-home inspections and interviews. DESIGN: Prospective cross
      sectional study. SETTING: Geriatric clinics at three university-affiliated
      hospitals. PARTICIPANTS: Consecutive community-dwelling outpatients 65 years or
      older who were newly referred. METHODS: The in-home medication inspection used a
      semistructured interview followed by a room-to-room search. The medications
      identified in the home were compared with the medication list derived in clinic
      by examination of the "medication bag" and interview. MAIN RESULTS: Fifty
      patients with a mean age of 78.9 years participated. The mean number of regular
      medications (prescription and nonprescription) was 6.3, and the mean number of
      regular prescription medications was 3.6. A comparison of clinic versus in-home
      medication lists revealed that 48% (95% confidence interval [95% CI], 34% to 62%)
      of patients had at least 1 omission of any regular medication and 19% (95%, CI
      10% to 32%) of patients had at least 1 omission of a regular prescription
      medication. CONCLUSION: The clinic-derived medication list resulted in a complete
      listing of all regular medications in only 52% taking regular medications. More
      specific instructions to patients to bring all prescription and nonprescription
      medications and all vitamins, herbal, and natural remedies, and more directed
      questions by physicians may result in more complete clinic medication lists.

PMID- 11251765
TI  - Can you keep a secret? Measuring the performance of those entrusted with personal
      health information.

PMID- 11251764
TI  - Evaluating and managing acute low back pain in the primary care setting.
AB  - Acute low back pain is a common reason for patient calls or visits to a primary
      care clinician. Despite a large differential diagnosis, the precise etiology is
      rarely identified, although musculoligamentous processes are usually suspected.
      For most patients, back symptoms are nonspecific, meaning that there is no
      evidence for radicular symptoms or underlying systemic disease. Because episodes
      of acute, nonspecific low back pain are usually self-limited, many patients treat
      themselves without contacting their primary care clinician. When patients do call
      or schedule a visit, evaluation and management by primary care clinicians is
      appropriate. The history and physical examination usually provide clues to the
      rare but potentially serious causes of low back pain, as well as to identify
      patients at risk for prolonged recovery. Diagnostic testing, including plain x
      rays, is often unnecessary during the initial evaluation. For patients with
      acute, nonspecific low back pain, the primary emphasis of treatment should be
      conservative care, time, reassurance, and education. Current recommendations
      focus on activity as tolerated (though not active exercise while pain is severe)
      and minimal if any bed rest. Referral for physical treatments is most appropriate
      for patients whose symptoms are not improving over 2 to 4 weeks. Specialty
      referral should be considered for patients with a progressive neurologic deficit,
      failure of conservative therapy, or an uncertain or serious diagnosis. The
      prognosis for most patients is good, although recurrence is common. Thus,
      educating patients about the natural history of acute low back pain and how to
      prevent future episodes can help ensure reasonable expectations.

PMID- 11251766
TI  - Limitations of information about health effects of chemicals.

PMID- 11251768
TI  - On Walsh JME, Wheat ME, Freud K. Detection, evaluation and treatment of eating
      disorders.

PMID- 11251767
TI  - Polypharmacy and medication adherence: small steps on a long road.

PMID- 11251770
TI  - An appraisal of the literature on centric relation. Part II.
AB  - The literature directly and indirectly related to centric relation (CR) has been
      reviewed chronologically. More than 300 papers and quoted sections of books have
      been divided into three sections. The first two parts of the paper are related to
      CR. Studies in this group mainly compared either the position of the mandibular
      condyle or the mandible itself in different CR recordings. Various tools were
      discussed for this purpose. The third part deals with CR-centric occlusion (CO)
      discrepancy. CR remains one of the controversial issues in prosthodontics and
      orthodontics. Debates relating to mounting casts on the articulator by
      reproducible records for orthodontic treatment planning and end results, and
      whether or not orthodontic treatment based on CO causes temporomandibular joint
      (TMJ) dysfunction, remain unsolved. The references are listed at the end of Part
      III.

PMID- 11251771
TI  - An in vitro assessment of the strength of porcelain veneers dependent on tooth
      preparation.
AB  - The treatment of teeth using veneer restorations combines aesthetic and
      functional improvements with a low destructive technique. Different kinds of
      tooth preparation techniques are described in the literature for this kind of
      restoration. This in vitro study aimed to examine the influence of the incisal
      preparation on the loadability of teeth restored with porcelain laminate veneers.
      Thirty-six selected mandibular incisors were randomly assigned to three groups
      with 12 teeth per group. In the first group, only the facial surface was
      prepared. In the second group, the preparation included a rounded incisal edge
      and a distinct chamfer lingually. The third group served as an unprepared
      control. Empress(R) veneers were then fabricated and cemented with a low viscous
      luting composite material. After 120 days storage in Ringer's solution, the
      specimens were loaded incisally to the point of failure. Statistical analysis of
      the results showed significant differences between the series (P=0.0103). Group 2
      (with preparation of the incisal edge) exhibited the lowest fracture resistance
      (466+/-99 N) (N, mean forces). When prepared only facially, the teeth restored
      with Empress veneers reached the strength of unprepared teeth. Compared with the
      biting force described for incisors in the literature, the in vitro loadability
      reached in this investigation seems to jusitify the clinical use of both
      preparation designs tested.

PMID- 11251773
TI  - Dynamic viscoelastic properties of photo-activated composite resins containing
      short glass fibres.
AB  - The dynamic shear modulus in torsion (G'), water absorption, thermal expansion
      and residual monomer of the reinforced materials produced by adding four short
      glass fibres (19 microm in mean diameter and 86.1--763 microm in mean length) and
      one spherical E glass (11.1 microm in mean diameter) were examined and discussed
      in comparison with those of the materials without filler. G' of short fibre
      reinforced composites increased with fibre length and reached a maximum value
      near 382 microm for a dry specimen and near 156 microm for a wet one. In
      addition, the coefficient of thermal expansion of the fibre reinforced composites
      and the amount of residual monomer decreased considerably compared with those of
      composites containing spherical glass. There was no significant difference in
      water absorption between the fibre reinforced composites and the composites
      containing spherical glass. Therefore, it was concluded that the reinforcement
      method of adding short glass fibres is favourable for improving the viscoelastic
      properties of the materials.

PMID- 11251772
TI  - Factors affecting the ability of dental cements to alter the pH of lactic acid
      solutions.
AB  - Two related studies have been carried out to determine the effect of (a)
      powder:liquid ratio and (b) relative amounts of cement on the extent of buffering
      of a lactic acid storage solution using zinc polycarboxylate and glass-ionomer
      cements (both water-activated). The effect of varying the powder:liquid ratio was
      found to be slight and not statistically significant. On the other hand,
      increasing the numbers of specimens in a given volume of storage solution was
      found to have a significant influence on the final pH (at the 0.0005 level of
      significance). The fact that powder:liquid ratio did not affect the final pH led
      to the conclusion that attack occurs mainly at the matrix of these cements,
      confirming previous findings about the acid erosion process. The finding that
      increasing the relative amount of cement to acid storage solution strongly
      influenced pH suggested that, under clinical conditions, buffering would be
      important. When five specimens were used, the final pH corresponded to that of
      arrested caries, from which it was concluded that these cements have the ability
      to be cariostatic in vivo.

PMID- 11251774
TI  - Influence of previous restoration of the tooth on prognosis of crowns with
      dowels.
AB  - Due to extensive loss of tooth substance the restoration of endodontically
      treated tooth requires intracanal dowels to give an efficient strength for the
      crown. The aim of our study was to investigate whether the previous type of
      restoration of the tooth, i.e. composite restoration with screw post versus one
      piece dowel crown, has an effect on the prognosis of crowns with dowels. The
      material consisted of 111 single crowns and as a previous restoration there were
      83 composite restorations with screw posts and 28 one-piece dowel crowns. The
      mean follow-up time was 78 months (range 6--163 months). The cumulative survival
      was 87% for one-piece dowel crowns and 84% for composite resins with screw posts.
      There were six root fractures, four losses of cement retention and one tooth
      extraction due to caries in crowns with previous composite resin with screw
      posts. In one-piece dowel crowns as a previous restoration there were two root
      fractures and one tooth extraction for periodontal reasons. In conclusion, it
      seems that the previous restoration has no marked effect on the prognosis of
      crowns with dowels when studying a composite resin restoration with screw post
      and a one-piece dowel crown.

PMID- 11251775
TI  - Effect of temperature and flux concentration on soldering of base metal.
AB  - The present study used the acoustic emission (AE) technique to evaluate
      interactions among soldering temperature, flux treatment, and the resultant
      ultimate tensile strength (UTS). Scanning electron microscopy (SEM) was used to
      examine fracture surfaces of the solder joints. Specimens were cast from
      removable partial denture alloy and then placed in a jig with a gap distance of
      1.0 mm. A high-frequency soldering machine with an optical pyrometer was used for
      soldering at 1150 degrees C and 1200 degrees C, respectively. The flux
      concentrations were 67% and 75%. The soldered specimens were subjected to tensile
      test at a crosshead speed of 0.05 mm/min. During testing, acoustic emissions in
      the frequency range of 100--1200 kHz were collected, filtered, recorded, and
      processed by a sensing device. The results were analysed by ANOVA and Tukey LSD
      test. UTS at different temperatures showed no significant difference according to
      either mechanical or acoustic results. But in the 1200 degrees C group, the UTSs
      and AE counts showed significant differences (P<0.05) at both flux
      concentrations. SEM showed that the 1200C group had better dendritic crystal
      structure than did the 1150 degrees C group. In the 1200 degrees C group
      specimens with 67% flux had fewer flux inclusion bodies and dendritic crystals
      than did specimens with 75% flux. The 75% flux subgroup produced high-amplitude
      (60--70 dB) acoustic signals within the elastic deformation zone, while the 67%
      flux subgroup produced similar signals within the plastic deformation zone,
      either beyond the 0.2% yield point or before fracture.

PMID- 11251776
TI  - Adhesive bonding of stainless steels and their component metals.
AB  - The purpose of the current study was to evaluate the bond strength of a metal
      adhesive system bonded to stainless steels and their component metals. Two sizes
      of disk specimens (10 and 8 mm in diameter x 2.5 mm thickness) were machined from
      two stainless steels designed for magnetic attachment (AUM20 and SUS 316L), as
      well as from high-purity chromium (Cr) and nickel (Ni) metals for reference. The
      specimens were air-abraded with alumina, either primed with a metal conditioner
      (Cesead II Opaque Primer) or left unprimed, and bonded with an adhesive resin
      (Super-Bond Opaque). Shear bond strengths were determined before and after
      thermocycling, and the results were analysed by analysis of variance (ANOVA).
      Post-thermocycling bond strengths of the unprimed groups were 16.3 MPa for the
      AUM20 alloy, 7.5 MPa for the SUS 316L alloy, 31.1 MPa for Cr and 3.1 MPa for Ni.
      Those of the conditioned groups were 30.3 MPa for the AUM20 alloy, 32.9 MPa for
      the SUS 316L alloy, 39.3 MPa for Cr and 13.1 MPa for Ni. Application of the
      conditioner elevated the bond strengths of all groups (P<0.05). It can be
      concluded that combined use of the conditioner and the Super-Bond adhesive is
      effective for bonding the stainless steels examined, and that Cr is a suitable
      component for the bonding system in question.

PMID- 11251777
TI  - Rheological characteristics of tooth bleaching materials.
AB  - Tooth bleaching materials need to flow easily on insertion but should have high
      viscosity at low stresses to stay in place on the teeth. Some degree of
      elasticity may also aid retention on the teeth thereby maximizing efficacy. The
      present work was undertaken to study the comparative rheology of three tooth
      bleaching systems: two gels (Opalescence, Ultradent; Perfecta Trio, American
      Dental Hygienics) and a paste (Colgate Platinum, Colgate). A dynamic stress
      rheometer (Rheometrics Scientific) with cone and plate geometry was used, with
      the materials maintained at 37.0+/-0.1 degrees C with a vapour hood to minimize
      volatilization. Stress creep and recovery experiments were carried out. Steady
      shear viscosity for all three systems was high (>10(6) Pa s(-1)) for stresses <20
      Pa. Between 100 and 200 Pa stress, all three materials showed a large drop in
      viscosity and flowed readily. The recovery portion of the data showed a marked
      difference where the elasticity of the gels was nearly two orders of magnitude
      higher than that of the paste. It was concluded that all materials would flow
      readily on insertion into the mouth and all have desirable high viscosity at low
      stress, but the paste material had the lowest elasticity. The effect of
      elasticity on performance needs to be determined clinically.

PMID- 11251778
TI  - Physical properties of resinous cements: an in vitro study.
AB  - The flow rate capacity, hydrolytic degradation and radiopacity of three resin
      based cements were tested and compared with zinc phosphate cement, when used in
      accordance with the manufacturer's instructions. There are no significant
      differences among the cements with regard to the flow rate. The zinc phosphate
      cement showed superior hydrolytic degradation compared with the other cements
      tested. The cements presented different radiopacities and the zinc phosphate
      cement was the most radiopaque. The results suggest that the development of resin
      based materials associated with adhesive procedures can increase the
      effectiveness of indirect restorations.

PMID- 11251779
TI  - Studies on cytotoxicity of nickel ions using C3H10T1/2 fibroblast cells.
AB  - Cytotoxicity of Ni ions were examined using C3H mouse derived 10T1/2 fibroblast
      cells. It became evident that Ni ions had dose-dependent cytotoxicity. The cell
      number incubated in DME medium containing 0.04 mM/L Ni ion for 6 days was reduced
      to half that in control DME medium without Ni. The cell totally disappeared in
      DME medium containing 2 mM/L Ni ion. The dissolution of Ni ions from Ni
      containing metallic restorations must be lower than these concentration levels so
      that oral tissues might not be damaged. No neoplastic transformation was found on
      all cells examined.

PMID- 11251780
TI  - Rehabilitation of biting abilities in patients with different types of dental
      prostheses.
AB  - This study investigated the masticatory rehabilitation of subjects wearing
      different types of prostheses. Biting abilities per person (biting force, biting
      pressure and occlusal contact area) were assessed with a pressure detecting sheet
      (Prescale(R)). Five hundred and ninety volunteers were divided into four groups
      according to the type of posterior dentition: complete denture, removable partial
      denture, fixed partial denture, and full natural dentition groups. The biting
      forces of the fixed partial, removable partial and complete denture wearers were
      80, 35 and 11% respectively, when expressed as a percentage of the subjects with
      a natural dentition. The complete denture wearers showed the highest biting
      pressure among the four groups, followed by the removable partial denture
      wearers. In a clinical intra-individual study, the biting abilities of 85
      subjects, without (before insertion of) and with (after insertion of) renewed
      prostheses, were compared. No significant differences were found between biting
      before and immediately after insertion of the prostheses. However, the biting
      force and occlusal contact area increased 2 months after insertion of the
      prostheses. This study confirmed past clinical studies indicating an impaired
      masticatory function of denture wearers. The functional adaptation to new
      prostheses had improved at evaluation 2 months after insertion.

PMID- 11251781
TI  - An investigation of temperature and stress distribution on a restored maxillary
      second premolar tooth using a three-dimensional finite element method.
AB  - This paper presents the stress analysis of the maxillary second premolar tooth
      under thermal loading as a result of hot/cold liquid in the mouth using the three
      dimensional (3D) finite element method (FEM). The tooth was considered to be in a
      restored state with composite resin and amalgam on glass-ionomer as the base
      material. In the first step of the study, the temperature changes as a result of
      hot/cold liquid in the mouth were calculated. The thermal stress distributions
      owing to the temperature changes were then obtained. All calculation programs
      were prepared by the authors using FORTRAN 77. The tooth was assumed to be
      isotropic, homogeneous, elastic and unsymmetric. The distribution of temperature
      and stress were plotted for some critical points.

PMID- 11251782
TI  - The genetic architecture of disease resistance in plants and the maintenance of
      recombination by parasites.
AB  - Parasites represent strong selection on host populations because they are
      ubiquitous and can drastically reduce host fitness. It has been hypothesized that
      parasite selection could explain the widespread occurrence of recombination
      because it is a coevolving force that favours new genetic combinations in the
      host. A review of deterministic models for the maintenance of recombination
      reveals that for recombination to be favoured, multiple genes that interact with
      each other must be under selection. To evaluate whether parasite selection can
      explain the maintenance of recombination, we review 85 studies that investigated
      the genetic architecture of plant disease resistance and discuss whether they
      conform to the requirements that emerge from theoretical models. General
      characteristics of disease resistance in plants and problems in evaluating
      resistance experimentally are also discussed. We found strong evidence that
      disease resistance in plants is determined by multiple loci. Furthermore, in most
      cases where loci were tested for interactions, epistasis between loci that affect
      resistance was found. However, we found weak support for the idea that specific
      allelic combinations determine resistance to different host genotypes and there
      was little data on whether epistasis between resistance genes is negative or
      positive. Thus, the current data indicate that it is possible that parasite
      selection can favour recombination, but more studies in natural populations that
      specifically address the nature of the interactions between resistance genes are
      necessary. The data summarized here suggest that disease resistance is a complex
      trait and that environmental effects and fitness trade-offs should be considered
      in future models of the coevolutionary dynamics of host and parasites.

PMID- 11251783
TI  - Genetic structure of the annual weed Senecio vulgaris in relation to habitat type
      and population size.
AB  - Throughout the world, the highly selfing annual common groundsel, Senecio
      vulgaris (Asteraceae) is a common weed. Recently, it has also colonized
      ecological compensation areas in agro-ecosystems. We investigated the genetic
      structure of S. vulgaris using random amplified polymorphic DNA (RAPD) profiles
      of 80 plants from nine populations representing three habitat types in two
      regions in Switzerland. RAPD variation among regions (19.8%), among populations
      within regions (19.2%) and within populations (61.1%) was highly significant
      (ANOVA; P < 0.001). Gene flow estimated from the observed differentiation among
      populations (PhiST = 0.382) was low (assuming Wright's island model, Nem =
      0.404). Genetic distances between pairs of populations were significantly
      correlated with geographical distances (Mantel test; r = 0.37, P < 0.03).
      Molecular variance obtained with AMOVA was lowest in the small populations in
      compensation areas (1.13), intermediate in vineyard populations (2.49), all
      located in northern Switzerland and highest in the larger vegetable field
      populations from western Switzerland (3.41; P < 0.05). Overall, there was a
      positive correlation of molecular variance and population size (P < 0.05), as
      expected under genetic drift. However, molecular variance was negatively
      correlated with population size among populations in ecological compensation
      areas, suggesting that selection was also important. We also applied triazine
      herbicide to leaves of three offspring of each of the 80 plants. Plants from
      populations of compensation areas showed higher mean levels and reduced variation
      in the resistance to triazine herbicide than plants from vineyards and vegetable
      fields. This suggests that compensation areas were colonized from adjacent corn
      fields, in which there has been selection for herbicide resistance. We discuss
      the implications of our results for the biological control of S. vulgaris.

PMID- 11251784
TI  - Partial nucleotide sequences, and routine typing by polymerase chain reaction
      restriction fragment length polymorphism, of the brown trout (Salmo trutta)
      lactate dehydrogenase, LDH-C1*90 and *100 alleles.
AB  - The cDNA nucleotide sequences of the lactate dehydrogenase alleles LDH-C1*90 and
      *100 of brown trout (Salmo trutta) were found to differ at position 308 where an
      A is present in the *100 allele but a G is present in the *90 allele. This base
      substitution results in an amino acid change from aspartic acid at position 82 in
      the LDH-C1 100 allozyme to a glycine in the 90 allozyme. Since aspartic acid has
      a net negative charge whilst glycine is uncharged, this is consistent with the
      electrophoretic observation that the LDH-C1 100 allozyme has a more anodal
      mobility relative to the LDH-C1 90 allozyme. Based on alignment of the cDNA
      sequence with the mouse genomic sequence, a local primer set was designed,
      incorporating the variable position, and was found to give very good
      amplification with brown trout genomic DNA. Sequencing of this fragment confirmed
      the difference in both homozygous and heterozygous individuals. Digestion of the
      polymerase chain reaction products with BslI, a restriction enzyme specific for
      the site difference, gave one, two and three fragments for the two homozygotes
      and the heterozygote, respectively, following electrophoretic separation. This
      provides a DNA-based means of routine screening of the highly informative LDH-C1*
      polymorphism in brown trout population genetic studies. Primer sets presented
      could be used to sequence cDNA of other LDH* genes of brown trout and other
      species.

PMID- 11251785
TI  - Genetic (RAPD) diversity in Peromyscus maniculatus populations in a naturally
      fragmented landscape.
AB  - We assessed the effects of long-term habitat fragmentation on genetic (random
      amplified polymorphic DNA) diversity in 11 Peromyscus maniculatus populations in
      the Lake Superior watershed. We analysed genetic structure at two spatial scales
      and the effect of island size and isolation on genetic diversity. At the regional
      scale, island populations differed from mainland populations (FST = 0.36), but
      mainland populations did not differ from each other (FST = 0.01). At the local
      scale, populations of the main island of Isle Royale differed from adjacent islet
      populations (P < 0.001; Monte Carlo approximation of Fisher's exact test), but
      not from each other (combined P = 0.63). Although geographical distance and
      genetic distance were positively correlated (P < 0.01; Mantel test), cluster
      analysis revealed some inconsistencies. Finally, genetic diversity was inversely
      related to isolation (P = 0.01), but had an unexpectedly negative relationship
      with island area (P = 0.03). The genetic structure of P. maniculatus populations
      in portions of the Lake Superior watershed appears to have been affected by long
      term habitat fragmentation.

PMID- 11251786
TI  - Microsatellite analysis of genetic variation among and within Alpine marmot
      populations in the French Alps.
AB  - The genetic structure of the Alpine marmot, Marmota marmota, was studied by an
      analysis of five polymorphic microsatellite loci. Eight locations were sampled in
      the French Alps, one from Les Ecrins valley (n = 160), another from La Sassiere
      valley (n = 289) and the six others from the Maurienne valley (n = 139).
      Information on social group structure was available for both Les Ecrins and La
      Sassiere but not for the other samples. The high levels of genetic diversity
      observed are at odds with the results obtained using microsatellites,
      minisatellites and allozymes on Alpine marmots from Germany, Austria and
      Switzerland. Strong deficits in heterozygotes were found in Les Ecrins and La
      Sassiere. They are caused by a Wahlund effect due to the family structure (i.e.
      differentiation between the family groups). The family groups exhibit excess of
      heterozygotes rather than deficits. This may be caused by outbreeding and this is
      compatible with recent results from the genetics of related social species when
      information on the social structure is taken into account. The observed
      outbreeding could be the result of females mating with transient males or males
      coming from neighbouring colonies. Both indicate that the species may not be as
      monogamous as is usually believed. The results are also compatible with a male
      biased dispersal but do not allow us to exclude some female migration. We also
      found a significant correlation between geographical and genetic distance
      indicating that isolation by distance could be an issue in marmots. This study is
      the first that analysed populations of marmots taking into account the social
      structure within populations and assessing inbreeding at different levels
      (region, valley, population, and family groups). Our study clearly demonstrated
      that the sampling strategy and behavioural information can have dramatic effects
      on both the results and interpretation of the genetic data.

PMID- 11251787
TI  - Genetic variation and population structure in Scandinavian wolverine (Gulo gulo)
      populations.
AB  - Wolverine (Gulo gulo) numbers in Scandinavia were significantly reduced during
      the early part of the century as a result of predator removal programmes and
      hunting. Protective legislation in both Sweden and Norway in the 1960s and 1970s
      has now resulted in increased wolverine densities in Scandinavia. We report here
      the development of 15 polymorphic microsatellite markers in wolverine and their
      use to examine the population sub-structure and genetic variability in free
      ranging Scandinavian wolverine populations as well as in a sample of individuals
      collected before 1970. Significant subdivision between extant populations was
      discovered, in particular for the small and isolated population of southern
      Norway, which represents a recent recolonization. Overall genetic variability was
      found to be lower than previously reported for other mustelids, with only two to
      five alleles per locus and observed heterozygosities (H(O)) ranging from 0.269 to
      0.376 across the examined populations, being lowest in southern Norway. Analysis
      of the mitochondrial DNA control region revealed no variation throughout the
      surveyed populations. As the historical sample did not show higher levels of
      genetic variability, our results are consistent with a reduction in the genetic
      variation in Scandinavian wolverines that pre-dates the demographic bottleneck
      observed during the last century. The observed subdivision between populations
      calls for management caution when issuing harvest quotas, especially for the
      geographically isolated south Norwegian population.

PMID- 11251788
TI  - Phylogeography, population history and conservation genetics of jaguars (Panthera
      onca, Mammalia, Felidae).
AB  - The jaguar (Panthera onca), the largest felid in the American Continent, is
      currently threatened by habitat loss, fragmentation and human persecution. We
      have investigated the genetic diversity, population structure and demographic
      history of jaguars across their geographical range by analysing 715 base pairs of
      the mitochondrial DNA (mtDNA) control region and 29 microsatellite loci in
      approximately 40 individuals sampled from Mexico to southern Brazil. Jaguars
      display low to moderate levels of mtDNA diversity and medium to high levels of
      microsatellite size variation, and show evidence of a recent demographic
      expansion. We estimate that extant jaguar mtDNA lineages arose 280 000-510 000
      years ago (95% CI 137 000-830 000 years ago), a younger date than suggested by
      available fossil data. No strong geographical structure was observed, in contrast
      to previously proposed subspecific partitions. However, major geographical
      barriers such as the Amazon river and the Darien straits between northern South
      America and Central America appear to have restricted historical gene flow in
      this species, producing measurable genetic differentiation. Jaguars could be
      divided into four incompletely isolated phylogeographic groups, and further
      sampling may reveal a finer pattern of subdivision or isolation by distance on a
      regional level. Operational conservation units for this species can be defined on
      a biome or ecosystem scale, but should take into account the historical barriers
      to dispersal identified here. Conservation strategies for jaguars should aim to
      maintain high levels of gene flow over broad geographical areas, possibly through
      active management of disconnected populations on a regional scale.

PMID- 11251789
TI  - Evolutionary history of the land snail Helix aspersa in the Western
      Mediterranean: preliminary results inferred from mitochondrial DNA sequences.
AB  - Intraspecific phylogeographic methods provide a means of examining the history of
      genetic exchange among populations. As part of a study of the history of Helix
      aspersa in the Western Mediterranean, we performed a phylogenetic analysis based
      on partial sequences of the mitochondrial large ribosomal subunit (16S) gene. Our
      samples include 31 H. a. aspersa populations from North Africa previously
      investigated for anatomical and biochemical characters. To clarify subspecific
      relationships, three individuals of the subspecies H. a. maxima were also
      studied. The molecular phylogeny inferred agrees largely with previous results,
      in splitting H. a. aspersa haplotypes into an eastern and a western group. H. a.
      maxima haplotypes form a third lineage arising before the H. a. aspersa groups.
      Divergence times estimated between the lineages suggest that dispersal during
      Pleistocene glaciation and vicariance events due to Pliocene geological changes
      in the western Mediterranean may both have played a significant part in the
      establishment of the present range of H. aspersa.

PMID- 11251791
TI  - Geographic pattern of genetic variation in Pinus resinosa: area of greatest
      diversity is not the origin of postglacial populations.
AB  - Genetic diversity is low in natural populations of red pine, Pinus resinosa, a
      species that has a vast range across north-eastern North America. In this study,
      we examined 10 chloroplast microsatellite or simple sequence repeats (cpSSR) loci
      in 136 individuals from 10 widespread populations. Substantial variation for the
      cpSSR loci was observed in the study populations. The contrast with red pine's
      lack of variation for other types of loci is likely to be due to the higher
      mutation rates typical of SSR loci. The amount of variation is lower than that
      generally found for cpSSR loci in other pine species. In addition, the variation
      exhibits a striking geographical pattern. Most of the genetic diversity is among
      populations, with little within populations, indicating substantial isolation of
      and genetic drift within many populations in the southern half of the species
      distribution. The greatest diversity now occurs in the north-eastern part of New
      England, which is especially intriguing because this entire area was glaciated.
      Thus the centre of diversity cannot be the origin of postglacial populations,
      rather it is likely caused by admixture, most probably because of influences from
      two separate refugia. Furthermore, the pattern indicates that the spread of red
      pine since the last glaciation is rather more complex than usually described, and
      it likely includes more than one refugia, complex migration routes, and
      postglacial-retreat isolation and genetic drift among shrinking populations in
      regions of the present southern range.

PMID- 11251790
TI  - Matrilinear phylogeography of Atlantic salmon (Salmo salar L.) in Europe and
      postglacial colonization of the Baltic Sea area.
AB  - Sixty-four samples from 46 salmon populations totalling 2369 specimens were used
      for polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      analysis of the mitochondrial ND1 region. The final analyses included 3095
      specimens from 60 populations in Northern Europe. A subsample was analysed by
      RFLP of ND3/4/5/6. Representative RFLP haplotypes from different parts of the
      distribution area were sequenced and the phylogeny of European haplotypes and
      their relations to the North American lineage was described. The four common
      European haplotypes derive from the ancestral ND1-BBBA (rooting the European
      clade to the North American) by one-step substitutions: AAAA < AABA < BBBA >
      BBBB. The Swedish west-coast populations differ from the geographically close
      southern Baltic, indicating absence of inward and limited outward gene flow
      through the Danish straits during the last 8000 years. Within the Baltic Sea,
      only three ND1 haplotypes were detected and there was no variation for ND3/4/5/6.
      In the whole southern Baltic and in lakes Vanern, Ladoga and Onega the haplotype
      AABA dominated. Proposed postglacial colonization routes to the Baltic Sea are
      discussed in relation to the haplotype distribution pattern.

PMID- 11251792
TI  - Nested clade analysis of the freshwater shrimp, Caridina zebra (Decapoda:
      Atyidae), from north-eastern Australia.
AB  - The freshwater shrimp, Caridina zebra, is endemic to montane rainforest streams
      of the Atherton Tableland, north-eastern Australia. As the confluences of many of
      the headwater streams are in unsuitable habitat, dispersal is expected to be
      highly restricted. Results from a previous allozyme survey for this species
      suggested that historical dispersal between separate river drainages had occurred
      due to rearrangements of the drainage lines at some stage in the recent past. The
      aim of this study was to use temporal information from the mitochondrial
      cytochrome oxidase subunit I (CO-I) gene to determine whether the observed
      genetic structure was a result of historical processes, or alternatively, due to
      low levels of terrestrial dispersal. The mitochondrial DNA (mtDNA) data were
      analysed using nested clade analysis, which can differentiate between historical
      fragmentation and range expansion vs. contemporary restricted gene flow. The
      results displayed three divergent clades that were likely to have arisen in
      allopatry. One widespread clade, with individuals in more than one river
      drainage, reflected a pattern of restricted gene flow. This suggests that this
      species is capable of terrestrial dispersal.

PMID- 11251793
TI  - Tripartite genetic subdivisions in the ornate shrew (Sorex ornatus).
AB  - We examined cytochrome b sequence variation in 251 ornate shrews (Sorex ornatus)
      from 20 localities distributed throughout their geographical range. Additionally,
      vagrant (S. vagrans) and montane (S. monticolus) shrews from four localities were
      used as outgroups. We found 24 haplotypes in ornate shrews from California (USA)
      and Baja California (Mexico) that differed by 1-31 substitutions in 392 bp of
      mitochondrial DNA (mtDNA) sequence. In a subset of individuals, we sequenced 699
      bp of cytochrome b to better resolve the phylogeographic relationships of
      populations. The ornate shrew is phylogeographically structured into three
      haplotype clades representing southern, central and northern localities. Analysis
      of allozyme variation reveals a similar pattern of variation. Several other small
      California vertebrates have a similar tripartite pattern of genetic subdivision.
      We suggest that topographic barriers and expansion and contraction of wetland
      habitats in the central valley during Pleistocene glacial cycles account for
      these patterns of genetic variation. Remarkably, the northern ornate shrew clade
      is phylogenetically clustered with another species of shrew suggesting that it
      may be a unique lowland form of the vagrant shrew that evolved in parallel to
      their southern California counterparts.

PMID- 11251795
TI  - Mating behaviour of Rhytidoponera sp. 12 ants inferred from microsatellite
      analysis.
AB  - In the queenless ponerine ant Rhytidoponera sp. 12, all workers have a
      spermatheca and functional ovaries and are potentially able to mate and
      reproduce. Within a colony gamergates may either be full sisters to each other
      (Type 1 colony), or they may not be full sisters but still be significantly
      related to each other (Type 2 colony) due to daughter gamergates reproducing in
      their natal colonies after mating. Despite many studies the mating behaviour of
      R. sp. 12 has been poorly understood. In this study, we used microsatellite
      markers to investigate intracolony relatednesses of male mates to the gamergates
      (bmq) and between male mates (bmm), and mating frequencies and mating patterns,
      using gamergate DNA and sperm DNA isolated from the spermathecae of gamergates
      from five colonies. Average bmm and bmq estimates for all five colonies studied
      were not significantly different from zero, suggesting that on average, within
      colonies, mating males were unrelated both to each other and to the gamergates. A
      low frequency (3%) of multiple mating by gamergates was detected. Multiple mating
      by individual males with sister gamergates within Type 1 colonies was also
      detected at 3% and could give rise to half-sister nestmate workers. Polygamy in
      R. sp. 12 might indicate local female-biased operational sex ratios despite the
      expectation of overall male biases. Our results concur with previous reports that
      gamergates mate within the colony or nearby, but indicate more diversity in
      mating patterns than previously indicated for this polygynous ponerine ant
      species.

PMID- 11251794
TI  - Evidence for broadscale introgressive hybridization between two redfish (genus
      Sebastes) in the North-west Atlantic: a rare marine example.
AB  - The evolutionary importance of introgressive hybridization has long been
      recognized by plant evolutionists, and there is now a growing recognition for its
      potential role in animals as well. Detailed empirical investigations of this
      evolutionary process, however, are still lacking in many animal groups,
      particularly in the marine environment. Using integrated microsatellite DNA data
      (eight loci analysed over 803 individuals representing 17 sampling locations) and
      multivariate statistical procedures (principal component, factorial
      correspondence and admixture proportion analyses), we: (i) provide a detailed
      dissection of the dynamics of introgressive hybridization between Sebastes
      fasciatus and S. mentella, two economically important redfishes from the North
      west Atlantic; and (ii) infer the factors potentially involved in the maintenance
      of the hybrid zone observed in the gulf of St. Lawrence and south of
      Newfoundland. This study provided one of the rare examples of extensive
      introgressive hybridization in the ocean, and highlighted the predominant role of
      this process in shaping the extent of genetic diversity, interspecific
      differences and population structuring among redfishes from the North-west
      Atlantic. The extensive (average rate of introgression = 15%) but geographically
      circumscribed and asymmetrical pattern of introgressive hybridization, the
      sympatric persistence of two reproductively isolated introgressed groups, the
      differential patterns of linkage disequilibrium among samples, and the
      maintenance of genetic integrity of both species outside the defined zone of
      introgression despite high potential for gene flow, all implicated selection in
      promoting and maintaining the observed pattern of introgression.

PMID- 11251796
TI  - Genetic evidence for a family structure in stable social aggregations of the
      Australian lizard Egernia stokesii.
AB  - In this study we used data from six unlinked microsatellite loci to examine
      stable aggregations of Egernia stokesii, from a population in the southern
      Flinders Ranges of South Australia. We show that these aggregations are comprised
      of breeding partners, their offspring from two or more cohorts, and related
      adults, providing the first genetic evidence of a family structure in any lizard
      species. Despite this high level of relatedness within aggregations, most
      breeding pairs were unrelated and partners were less closely related to each
      other than they were to other potential within-group partners. Where individuals
      dispersed, both sexes usually moved to social groups close to their natal group.
      Although both sexes showed natal philopatry, there was some evidence that females
      in groups were more related than males in groups. These data suggest that an
      active choice of unrelated partners and male-biased dispersal may be the
      mechanisms used by E. stokesii to avoid inbreeding within groups.

PMID- 11251797
TI  - Swarm-founding in the polistine wasps: the importance of finding many
      microsatellite loci in studies of adaptation.
AB  - We developed 52 microsatellite loci for the wasp, Polybioides tabidus, for the
      purpose of studying the evolution and inclusive fitness consequences of swarm
      founding. The large number of loci is important for three reasons that may apply
      to many other systems. Heterozygosity was low in our target species, yet we found
      enough polymorphic loci for accurate kinship studies in this species. Many
      monomorphic loci were polymorphic in other polistine wasps, making comparative
      studies possible. Finally, enough loci amplified over a broad range of species to
      add a historical dimension. We sequenced six loci in other polistine wasps and
      used the flanking sequences to construct a phylogeny. Based on this phylogeny, we
      infer that swarm-founding has evolved independently three times in the polistine
      wasps.

PMID- 11251799
TI  - Patterns and levels of gene flow in Rhododendron metternichii var. hondoense
      revealed by microsatellite analysis.
AB  - Parentage analysis was conducted to elucidate the patterns and levels of gene
      flow in Rhododendron metternichii Sieb. et Zucc. var. hondoense Nakai in a 150 x
      70 m quadrant in Hiroshima Prefecture, western Japan. The population of R.
      metternichii occurred as three subpopulations at the study site. Seventy
      seedlings were randomly collected from each of three 10 x 10 m plots (S1, S2, and
      S3) on the forest floor of each subpopulation (A1, A2, and A3). Almost all
      parents (93.8%) of the 70 seedlings were unambiguously identified by using 12
      pairs of microsatellite markers. Within the quadrant, adult trees less than 5 m
      from the centre of the seedling bank (plots S1, S2, and S3) produced large
      numbers of seedlings. The effects of tree height and distance from the seedling
      bank on the relative fertilities of adult trees were highly variable among
      subpopulations because of the differences in population structure near the
      seedling bank: neither distance nor tree height had any significant effect in
      subpopulation A1; distance from the seedling bank had a significant effect in
      subpopulation A2; and tree height had a significant effect in subpopulation A3.
      Although gene flow within each subpopulation was highly restricted to less than
      25 m and gene flow among the three subpopulations was extremely small (0-2%),
      long-distance gene flow from outside the quadrant reached 50%. This long-distance
      gene flow may be caused by a combination of topographical and vegetational
      heterogeneity, differences in flowering phenology, and genetic substructuring
      within subpopulations.

PMID- 11251798
TI  - Microsatellite determination of male reproductive success in a natural population
      of the territorial ornate dragon lizard, Ctenophorus ornatus.
AB  - It is now evident that the genetic mating system can be very different to the
      observed mating system. However, it is less well known what makes particular
      individuals more (or less) successful than expected from the observed system. In
      this study the observed territorial structure of a field population of the agamid
      lizard, Ctenophorus ornatus, was compared with the mating system as evidenced by
      microsatellite parentage assignment. This study also investigated whether any
      male traits predicted reproductive success. Sixty-five per cent of clutches were
      sired at least partially by a male other than the main territory-holding male and
      35% of clutches were sired by a male with no overlap of the female's territory.
      Multiple paternity was moderately frequent at 25% of clutches. Male chest patch
      size predicted territory size and the number of females in the territory, but did
      not predict reproductive success. Instead, male head depth and body size were
      independently related to the number of offspring sired. As male head depth also
      predicted the number of females in a territory, these males are likely to be
      gaining increased reproductive success as a consequence of the higher number of
      females in their territories. Larger body size males, however, did not have a
      greater number of females in their territory and instead had more extra
      territorial copulations. Whether these extra-territorial copulations are due to
      female choice or success in male competition is unknown.

PMID- 11251800
TI  - Independent origins and horizontal transfer of bacterial symbionts of aphids.
AB  - Many insect groups have obligate associations with primary endosymbionts:
      mutualistic bacteria that are maternally transmitted and derived from an ancient
      infection. Often, the same insects are hosts to 'secondary' bacterial symbionts
      which are maternally transmitted but relatively labile within host lineages. To
      explore the dynamics of secondary symbiont associations in aphids, we
      characterized bacteria infecting 15 species of macrosiphine aphids using DNA
      sequencing, diagnostic polymerase chain reaction (PCR), diagnostic restriction
      digests, phylogenetic analyses, and electron microscopy to examine aphids from
      nature and from laboratory colonies. Three types of bacteria besides Buchnera
      were found repeatedly; all three fall within the Enterobacteriaceae. The R-type
      has a 16S rDNA less than 0.1% different from that of the secondary symbiont
      previously reported from Acyrthosiphon pisum and is related to Serratia species.
      The T-type includes a symbiont previously reported from a whitefly; the U-type
      comprises a new cluster near the T-type. The T-type was found in every one of 40
      Uroleucon ambrosiae clones collected throughout the United States. In contrast,
      A. pisum individuals were infected by any combination of the three symbiont
      types. Secondary symbionts were maternally transmitted for 11 months within
      laboratory-reared A. pisum clones and were present in sexually produced eggs. PCR
      screens for a bacteriophage, APSE-1, indicated its presence in both A. pisum and
      U. ambrosiae containing secondary symbionts. Electron microscopy of R-type and T
      type bacteria in A. pisum and in U. ambrosiae revealed rod-shaped organisms that
      attain extremely high densities within a few bacteriocytes.

PMID- 11251801
TI  - Use of amplified fragment length polymorphism markers to assess genetic diversity
      of Lolium species from Portugal.
AB  - We evaluated the use of amplified fragment length polymorphism (AFLP) markers to
      distinguish genotypes, populations and species of Lolium. Accessions of two
      species Lolium perenne and Lolium multiflorum and their hybrid Lolium x hybridum,
      collected by the Institute of Grass and Environmental Research in 1995 from
      locations across Portugal, were used. The genetic variation within and between
      populations from the extremes of latitude and altitude was determined and
      assessed. Three primer pair combinations generated 765 polymorphic bands.
      Principal coordinate analysis of similarities between 127 plants showed high
      dimensionality in the data. Axes 1-3 were associated primarily with species
      differences, axes 4-14 with population differences within species and axis 15
      onwards with within population differences. UPGMA analysis confirmed the
      groupings. The three populations of L. perenne formed a discrete cluster widely
      separated from all other populations. There were two distinct groups of L. x
      hybridum, of which one was similar to and overlapped with L. multiflorum and the
      second formed a distinct cluster. Analyses of individual bands showed that every
      inter- and intraspecific contrast involved a different sets of bands, again
      confirming the high dimensionality of the data. No single band was strictly
      diagnostic of any population or species. Nevertheless, the UPGMA analysis showed
      little or no overlap between populations. Thus, despite the high ratio of within
      to-between population genetic variance, the full AFLP banding pattern of each
      genotype is a relatively reliable fingerprint diagnostic of its parent
      population. The high dimensionality implies that many different factors
      contribute to the differences observed. This adds to the potential value of the
      methodology, since it implies that there is a reasonably high likelihood of
      finding bands relevant to a given environmental gradient or other factor
      influencing the distribution of genetic diversity.

PMID- 11251802
TI  - Molecular genetic markers provide no evidence for reproductive isolation among
      retreat building phenotypes of the net-spinning caddisfly Macrostemum carolina.
AB  - Larvae of the stream-dwelling, filter-feeding caddisfly Macrostemum carolina
      construct silken catchnets within protective retreats. In the Savannah River, M.
      carolina individuals make three different retreats, each with a distinct water
      entrance hole: (i) at the end of a silken tube; (ii) with a approximately 180
      degrees silken backstop; and (iii) flush with the top of the retreat. To resolve
      whether these different retreats represent alternative behavioural phenotypes
      within a single panmictic population or fixed phenotypes within three genetically
      distinct populations or species, we compared the allele frequencies at three
      polymorphic nuclear loci (allozyme electrophoresis for Gpi, Mpi and Pgm) and the
      mitochondrial DNA (mtDNA) haplotype frequencies among individuals displaying the
      three retreat morphs. We also calculated pairwise exact tests of population
      differentiation using the allozyme and mtDNA allele frequencies. No significant
      genetic differentiation was detected among caddisflies exhibiting the different
      retreat morphs. Therefore, these morphs apparently represent a single panmictic
      population in the Savannah River. Consequently, additional study is required to
      assess whether this retreat polymorphism is a phenotypically plastic trait under
      conditional control, or is mediated by alternative alleles at a Mendelian gene or
      genes (or a combination of the two).

PMID- 11251803
TI  - Estimating the probability of identity among genotypes in natural populations:
      cautions and guidelines.
AB  - Individual identification using DNA fingerprinting methods is emerging as a
      critical tool in conservation genetics and molecular ecology. Statistical methods
      that estimate the probability of sampling identical genotypes using theoretical
      equations generally assume random associations between alleles within and among
      loci. These calculations are probably inaccurate for many animal and plant
      populations due to population substructure. We evaluated the accuracy of a
      probability of identity (P(ID)) estimation by comparing the observed and expected
      P(ID), using large nuclear DNA microsatellite data sets from three endangered
      species: the grey wolf (Canis lupus), the brown bear (Ursus arctos), and the
      Australian northern hairy-nosed wombat (Lasiorinyus krefftii). The theoretical
      estimates of P(ID) were consistently lower than the observed P(ID), and can
      differ by as much as three orders of magnitude. To help researchers and managers
      avoid potential problems associated with this bias, we introduce an equation for
      P(ID) between sibs. This equation provides an estimator that can be used as a
      conservative upper bound for the probability of observing identical multilocus
      genotypes between two individuals sampled from a population. We suggest computing
      the actual observed P(ID) when possible and give general guidelines for the
      number of codominant and dominant marker loci required to achieve a reasonably
      low P(ID) (e.g. 0.01-0.0001).

PMID- 11251804
TI  - Tandem repeats in plant mitochondrial genomes: application to the analysis of
      population differentiation in the conifer Norway spruce.
AB  - Mitochondrial DNA, widely applied in studies of population differentiation in
      animals, is rarely used in plants because of its slow rate of sequence evolution
      and its complex genomic organization. We demonstrate the utility of two
      polymorphic mitochondrial tandem repeats located in the second intron of the nad1
      gene of Norway spruce. Most of the size variants showed pronounced population
      differentiation and a distinct geographical distribution. A GenBank search
      revealed that mitochondrial tandem repeats occur in a broad range of plant
      species and may serve as a novel molecular marker for unravelling population
      processes in plants.

PMID- 11251805
TI  - The X philes: structure-specific endonucleases that resolve Holliday junctions.
AB  - Genetic recombination is a critical cellular process that promotes evolutionary
      diversity, facilitates DNA repair and underpins genome duplication. It entails
      the reciprocal exchange of single strands between homologous DNA duplexes to form
      a four-way branched intermediate commonly referred to as the Holliday junction.
      DNA molecules interlinked in this way have to be separated in order to allow
      normal chromosome transmission at cell division. This resolution reaction is
      mediated by structure-specific endonucleases that catalyse dual-strand incision
      across the point of strand cross-over. Holliday junctions can also arise at
      stalled replication forks by reversing the direction of fork progression and
      annealing of nascent strands. Resolution of junctions in this instance generates
      a DNA break and thus serves to initiate rather than terminate recombination.
      Junction resolvases are generally small, homodimeric endonucleases with a high
      specificity for branched DNA. They use a metal-binding pocket to co-ordinate an
      activated water molecule for phosphodiester bond hydrolysis. In addition, most
      junction endonucleases modulate the structure of the junction upon binding, and
      some display a preference for cleavage at specific nucleotide target sequences.
      Holliday junction resolvases with distinct properties have been characterized
      from bacteriophages (T4 endo VII, T7 endo I, RusA and Rap), Bacteria (RuvC),
      Archaea (Hjc and Hje), yeast (CCE1) and poxviruses (A22R). Recent studies have
      brought about a reappraisal of the origins of junction-specific endonucleases
      with the discovery that RuvC, CCE1 and A22R share a common catalytic core.

PMID- 11251806
TI  - Calcineurin regulatory subunit is essential for virulence and mediates
      interactions with FKBP12-FK506 in Cryptococcus neoformans.
AB  - Calcineurin is a Ca2+-calmodulin-regulated protein phosphatase that is the target
      of the immunosuppressive drugs cyclosporin A and FK506. Calcineurin is a
      heterodimer composed of a catalytic A and a regulatory B subunit. In previous
      studies, the calcineurin A homologue was identified and shown to be required for
      growth at 37 degrees C and hence for virulence of the pathogenic fungus
      Cryptococcus neoformans. Here, we identify the gene encoding the calcineurin B
      regulatory subunit and demonstrate that calcineurin B is also required for growth
      at elevated temperature and virulence. We show that the FKR1-1 mutation, which
      confers dominant FK506 resistance, results from a 6 bp duplication generating a
      two-amino-acid insertion in the latch region of calcineurin B. This mutation was
      found to reduce FKBP12-FK506 binding to calcineurin both in vivo and in vitro.
      Molecular modelling based on the FKBP12-FK506-calcineurin crystal structure
      illustrates how this mutation perturbs drug interactions with the phosphatase
      target. In summary, our studies reveal a central role for calcineurin B in
      virulence and antifungal drug action in the human fungal pathogen C. neoformans.

PMID- 11251807
TI  - The variable P5 proteins of typeable and non-typeable Haemophilus influenzae
      target human CEACAM1.
AB  - Haemophilus influenzae, a commensal of the human respiratory mucosa, is an
      important cause of localized and systemic infections. We have recently shown that
      numerous strains of capsulate (typeable) and acapsulate (non-typeable) H.
      influenzae target the carcinoembryonic antigen (CEA) family of cell adhesion
      molecules (CEACAMs). Moreover, the ligands appeared to be antigenically variable
      and, when using viable typeable bacteria, their adhesive functions were inhibited
      by the presence of capsule. In this report, we show that the antigenically
      variable outer membrane protein, P5, expressed by typeable and non-typeable H.
      influenzae targets human CEACAM1. Variants and mutants lacking the expression of
      P5 of all strains tested were unable to target purified soluble receptors. A non
      typeable strain that did not interact with CEACAM1 was made adherent to both the
      soluble receptors and CEACAM1-transfected Chinese hamster ovary cells by
      transformation with the P5 gene derived from the adherent typeable strain Rd.
      However, several H. influenzae mutants lacking P5 expression continued to bind
      the cell-bound CEACAM1 receptors. These observations suggest that (i) CEACAM1
      alone can support P5 interactions and (ii) some strains contain additional
      ligands with the property to target CEACAM1 but require the receptor in the
      cellular context. The identification of a common ligand in diverse strains of H.
      influenzae and the presence of multiple ligands for the same receptor suggests
      that targeting of members of the CEACAM family of receptors may be of primary
      significance in colonization and pathogenesis of H. influenzae strains.

PMID- 11251808
TI  - Two different pathways are involved in the beta-oxidation of n-alkanoic and n
      phenylalkanoic acids in Pseudomonas putida U: genetic studies and
      biotechnological applications.
AB  - In Pseudomonas putida U, the degradation of n-alkanoic and n-phenylalkanoic acids
      is carried out by two sets of beta-oxidation enzymes (betaI and betaII). Whereas
      the first one (called betaI) is constitutive and catalyses the degradation of n
      alkanoic and n-phenylalkanoic acids very efficiently, the other one (betaII),
      which is only expressed when some of the genes encoding betaI enzymes are
      mutated, catabolizes n-phenylalkanoates (n > 4) much more slowly. Genetic studies
      revealed that disruption or deletion of some of the betaI genes handicaps the
      growth of P. putida U in media containing n-alkanoic or n-phenylalkanoic acids
      with an acyl moiety longer than C4. However, all these mutants regained their
      ability to grow in media containing n-alkanoates as a result of the induction of
      betaII, but they were still unable to catabolize n-phenylalkanoates completely,
      as the betaI-FadBA enzymes are essential for the beta-oxidation of certain n
      phenylalkanoyl-CoA derivatives when they reach a critical size. Owing to the
      existence of the betaII system, mutants lacking betaIfadB/A are able to
      synthesize new poly 3-OH-n-alkanoates (PHAs) and poly 3-OH-n-phenylalkanoates
      (PHPhAs) efficiently. However, they are unable to degrade these polymers,
      becoming bioplastic overproducer mutants. The genetic and biochemical importance
      of these results is reported and discussed.

PMID- 11251809
TI  - Selective expression of the virulence factor BAD1 upon morphogenesis to the
      pathogenic yeast form of Blastomyces dermatitidis: evidence for transcriptional
      regulation by a conserved mechanism.
AB  - Most dimorphic fungal pathogens grow as non-pathogenic moulds in soil and convert
      to pathogenic yeast in the host, suggesting that virulence factors are
      upregulated during phase transition. Such factors have been difficult to
      identify. We analysed BAD1 (formerly WI-1), a virulence factor in the dimorphic
      fungus Blastomyces dermatitidis, for expression in yeast and mycelial
      morphotypes. BAD1 was expressed in yeast but not in mycelia of North American
      strains of B. dermatitidis, and this expression pattern was confirmed for BAD1
      transcript. BAD1 under the control of its promoter was transferred into African
      B. dermatitidis lacking a native BAD1 locus, and phase-specific expression was
      conserved. Sequence similarity was identified between the BAD1 promoter and the
      promoters of two yeast phase-specific genes in Histoplasma capsulatum. In H.
      capsulatum BAD1 transformants, yeast phase-specific expression of BAD1 was
      conserved, and no transcript was detected in mycelia. BAD1 beta-galactosidase
      reporter fusions analysed in B. dermatitidis and H. capsulatum confirmed that
      BAD1 is transcriptionally regulated in both fungi. BAD1 promoter activity and
      surface BAD1 expression were detected 6 h after shifting mycelia to 37 degrees C.
      Thus, BAD1 is expressed after transition to the pathogenic yeast morphotype and
      is regulated by a mechanism for phase-specific gene expression that appears to be
      conserved.

PMID- 11251811
TI  - Interplay between recombination, cell division and chromosome structure during
      chromosome dimer resolution in Escherichia coli.
AB  - Chromosome dimers form in bacteria by recombination between circular chromosomes.
      Resolution of dimers is a highly integrated process involving recombination
      between dif sites catalysed by the XerCD recombinase, cell division and the
      integrity of the division septum-associated FtsK protein and the presence of dif
      inside a restricted region of the chromosome terminus, the dif activity zone
      (DAZ). We analyse here how these phenomena collaborate. We show that (i) both
      inter- and intrachromosomal recombination between dif sites are activated by
      their presence inside the DAZ; (ii) the DAZ-specific activation only occurs in
      conditions supporting the formation of chromosome dimers; (iii) overexpression of
      FtsK leads to a general increase in dif recombination irrespective of dif
      location; (iv) overexpression of FtsK does not improve the ability of dif sites
      inserted outside the DAZ to resolve chromosome dimers. Our results suggest that
      the formation of an active XerCD-FtsK-dif complex is restricted to when a dimer
      is present, the features of chromosome organization that determine the DAZ
      playing a central role in this control.

PMID- 11251810
TI  - Probing the mechanism of ATP hydrolysis and substrate translocation in the AAA
      protease FtsH by modelling and mutagenesis.
AB  - We have built a homology model of the AAA domain of the ATP-dependent protease
      FtsH of Escherichia coli based on the crystal structure of the hexamerization
      domain of N-ethylmaleimide-sensitive fusion protein. The resulting model of the
      hexameric ring of the ATP-bound form of the AAA ATPase suggests a plausible
      mechanism of ATP binding and hydrolysis, in which invariant residues of Walker
      motifs A and B and the second region of homology, characteristic of the AAA
      ATPases, play key roles. The importance of these invariant residues was confirmed
      by site-directed mutagenesis. Further modelling suggested a mechanism by which
      ATP hydrolysis alters the conformation of the loop forming the central hole of
      the hexameric ring. It is proposed that unfolded polypeptides are translocated
      through the central hole into the protease chamber upon cycles of ATP hydrolysis.
      Degradation of polypeptides by FtsH is tightly coupled to ATP hydrolysis, whereas
      ATP binding alone is sufficient to support the degradation of short peptides.
      Furthermore, comparative structural analysis of FtsH and a related ATPase, HslU,
      reveals interesting similarities and differences in mechanism.

PMID- 11251812
TI  - Activation of heat shock transcription factor in yeast is not influenced by the
      levels of expression of heat shock proteins.
AB  - Heat shock transcription factor (HSF) transiently induces the expression of a
      universally conserved set of proteins, the heat shock proteins (Hsps), when cells
      are exposed to elevated temperatures as well as to a wide range of other
      environmental stresses. The tight control of heat shock gene expression has
      prompted a model, according to which HSF activity and 'free' heat shock protein
      levels are tied up in a regulatory loop. Other data have indicated that HSF
      senses stress directly. Here, we report that yeast cells in which the basal
      expression levels of Hsps have been significantly increased exhibit improved
      thermotolerance but display no detectable difference in the temperature required
      for transient activation of HSF. In a separate experiment, overexpression of
      SSA2, a member of the Hsp70 family and a prominent candidate for the feedback
      regulation of HSF, did not inhibit the heat shock response. Our findings
      challenge the dogma that relief of the suppression of HSF activity by Hsps can
      account for the acute heat shock response.

PMID- 11251813
TI  - Alanine scan mutagenesis of the switch I domain of the Caulobacter crescentus
      CgtA protein reveals critical amino acids required for in vivo function.
AB  - The Caulobacter crescentus CgtA protein is a member of the Obg/GTP1 subfamily of
      monomeric GTP-binding proteins. In vitro, CgtA displays moderate affinity for
      both GDP and GTP and displays rapid exchange rate constants for either
      nucleotide, indicating that the guanine nucleotide-binding and exchange
      properties of CgtA are different from those of the well-characterized Ras-like
      GTP-binding proteins. The Obg/GTP1 proteins share sequence similarity along the
      putative effector-binding domain. In this study, we examined the functional
      consequences of altering amino acid residues within this conserved domain, and
      identified that T193 was critical for CgtA function. The in vitro binding,
      exchange and GTP hydrolysis of the T192A, T193A and T192AT193A mutant proteins
      was examined using fluorescent guanine nucleotide analogues (mant-GDP and mant
      GTP). Substitution of either T192 and/or T193 for alanine modestly reduced
      binding to GDP and significantly reduced the binding affinity for GTP.
      Furthermore, the T193A mutant protein was more severely impaired for binding GTP
      than the T192A mutant. The T193A mutation appeared to account solely for the
      impaired GTP binding of the T192AT193A double mutation. This is the first report
      that demonstrates that a confirmed defect in guanine nucleotide binding and GTP
      hydrolysis of an Obg-like protein results in the lack of function in vivo.

PMID- 11251814
TI  - Characterization of the A2-A2rel gene cluster in Leishmania donovani: involvement
      of A2 in visceralization during infection.
AB  - The A2 gene family is present in Leishmania donovani, which causes fatal visceral
      leishmaniasis in human patients, but is not present in Leishmania major, which
      causes cutaneous leishmaniasis infections. The A2 genes in L. donovani are stage
      specific and are expressed at high levels in the amastigote stage in the
      mammalian host, but are not expressed in the promastigote stage in the insect
      sandfly vector. The A2 genes are tandem repeated with a distinct gene family
      termed the A2rel genes. In order to characterize the structure and function of
      the A2-A2rel gene clusters, the 5' and 3' DNA sequences flanking the A2-A2rel
      cluster were isolated, sequenced and used to generate mutants through gene
      targeting. Although it was possible to generate partial A2-A2rel gene clusters
      knock-out mutants, it was not possible to delete all the A2-A2rel gene clusters
      completely from the L. donovani genome, suggesting that, within this cluster,
      there are genes that are essential for survival in culture. Characterization of
      these mutants revealed that A2 and A2rel gene expression was compensated by
      amplifying the remaining intact A2 and A2rel genes, and the proliferation of
      these mutants in culture and their virulence in BALB/c mice were compromised. In
      order to explore further the biological role of A2, the L. donovani A2 gene was
      introduced into L. major. In comparison with the control L. major, the A2
      expressing L. major parasites demonstrated an increased ability to survive in the
      spleen of BALB/c mice. These data suggest that A2 plays a role in the
      visceralization of infection associated with L. donovani.

PMID- 11251815
TI  - Cell cycle and positional constraints on FtsZ localization and the initiation of
      cell division in Caulobacter crescentus.
AB  - Swarmer cells of Caulobacter crescentus are devoid of the cell division
      initiation protein FtsZ and do not replicate DNA. FtsZ is synthesized during the
      differentiation of swarmer cells into replicating stalked cells. We show that
      FtsZ first localizes at the incipient stalked pole in differentiating swarmer
      cells. FtsZ subsequently localizes at the mid-cell early in the cell cycle. In an
      effort to understand whether Z-ring formation and cell constriction are driven
      solely by the cell cycle-regulated increase in FtsZ concentration, FtsZ was
      artificially expressed in swarmer cells at a level equivalent to that found in
      predivisional cells. Immunofluorescence microscopy showed that, in these swarmer
      cells, simply increasing FtsZ concentration was not sufficient for Z-ring
      formation; Z-ring formation took place only in stalked cells. Expression of FtsZ
      in swarmer cells did not alter the timing of cell constriction initiation during
      the cell cycle but, instead, caused additional constrictions and a delay in cell
      separation. These additional constrictions were confined to sites close to the
      original mid-cell constriction. These results suggest that the timing and
      placement of Z-rings is tightly coupled to an early cell cycle event and that
      cell constriction is not solely dependent on a threshold level of FtsZ.

PMID- 11251816
TI  - SoxR-dependent response to oxidative stress and virulence of Erwinia
      chrysanthemi: the key role of SufC, an orphan ABC ATPase.
AB  - Erwinia chrysanthemi causes soft-rot disease in a great variety of plants. In
      addition to the depolymerizing activity of plant cell wall-degrading enzymes,
      iron acquisition and resistance to oxidative stress contribute greatly to the
      virulence of this pathogen. Here, we studied the pin10 locus originally thought
      to encode new virulence factors. The sequence analysis revealed six open reading
      frames that were homologous to the Escherichia coli sufA, sufB, sufC, sufD, sufS
      and sufE genes. Sequence similarity searching predicted that (i) SufA, SufB,
      SufD, SufS and SufE proteins are involved in iron metabolism and possibly in Fe-S
      cluster assembly; and (ii) SufC is an ATPase of an ABC transporter. The reverse
      transcription-polymerase chain reaction procedure showed that the sufABCDSE genes
      constitute an operon. Expression of a sufB:uidA fusion was found to be induced in
      iron-deficient growth conditions and to be repressed by the iron-sensing Fur
      repressor. Each of the six suf genes was inactivated by the insertion of a
      cassette generating a non-polar mutation. The intracellular iron level in the
      sufA, sufB, sufC, sufS and sufE mutants was higher than in the wild type, as
      assessed by increased sensitivity to the iron-activated antibiotic streptonigrin.
      In addition, inactivation of sufC and sufD led to increased sensitivity to
      paraquat. Virulence tests showed that sufA and sufC mutants exhibited reduced
      ability to cause maceration of chicory leaves, whereas a functional sufC gene was
      necessary for the bacteria to cause systemic invasion of Saintpaulia ionantha.
      The E. coli sufC homologue was inactivated by reverse genetic. This mutation was
      found to modify the soxR-dependent induction of soxS gene expression. We discuss
      the possibility that SufC is a versatile ATPase that can associate either with
      the other Suf proteins to form a Fe-S cluster-assembling machinery or with
      membrane proteins encoded elsewhere in the chromosome to form an Fe-S ABC
      exporter. Overall, these results stress the importance of the connection between
      iron metabolism and oxidative stress during the early steps of infection by E.
      chrysanthemi.

PMID- 11251817
TI  - Plasmodium protein phosphatase 2C dephosphorylates translation elongation factor
      1beta and inhibits its PKC-mediated nucleotide exchange activity in vitro.
AB  - The elongation step of protein synthesis involves binding of aminoacyl-tRNA to
      the ribosomal A site, formation of a peptide bond and translocation of the newly
      formed peptidyl-tRNA to the P site. The nucleotide exchange factor EF-1beta plays
      a major role in the regulation of this process by regenerating a GTP-bound EF
      1alpha necessary for each elongation cycle. EF-1beta has been shown to be
      phosphorylated and its phosphorylation is critical for optimal activity. We have
      previously identified a serine/threonine protein phosphatase 2C (PP2C) from the
      human malaria parasite Plasmodium falciparum. In the current work, we performed
      Far-Western analysis to identify PfPP2C substrates. Several components of the
      translation and transcription machinery were identified, including translation
      elongation factor 1-beta (PfEF-1beta). PfEF-1beta is efficiently phosphorylated
      by protein kinase C and this phosphorylation results in a 400% increase in its
      nucleotide exchange activity. PKC-phosphorylated PfEF-1beta is readily and
      selectively dephosphorylated by recombinant and native PfPP2C, which
      downregulates the nucleotide exchange activity to its basal level. The
      identification of a translation elongation component as substrate for PP2C
      suggests an important regulatory function for this enzyme and suggests that it
      may be a good target for drug design in the fight against malaria.

PMID- 11251818
TI  - Regulation of immunity to the two-component lantibiotic, lacticin 3147, by the
      transcriptional repressor LtnR.
AB  - Lacticin 3147 is a membrane-active, two-component lantibiotic produced by
      Lactococcus lactis ssp. lactis DPC3147. In this study, the promoters of the
      lacticin 3147 gene cluster were mapped to the intergenic region between ltnR and
      ltnA1 (the genes encoding the regulatory protein LtnR and the first structural
      gene, LtnA1), and Northern analyses revealed that the biosynthetic and immunity
      genes are divergently transcribed in two operons, ltnA1A2M1TM2D and ltnRIFE
      respectively. Although the promoter controlling biosynthesis (Pbac) appears to be
      constitutive, characterization of a downstream beta-galactosidase (beta-gal)
      fusion beyond an intragenic stem-loop structure in ltnM1 confirmed that this
      putative transcriptional attenuator allows limited readthrough to the downstream
      biosynthetic genes, thus maintaining the correct stoichiometry between structural
      peptides and biosynthetic machinery. The promoter of the ltnRIFE operon (Pimm)
      was shown to be regulated by the transcriptional repressor LtnR. A mutant with a
      truncated ltnR gene exhibited a hyperimmune phenotype, whereas overexpression of
      ltnR resulted in cells with increased sensitivity to lacticin 3147. Gel mobility
      shift analysis indicated that LtnR binds to the Pimm promoter region, and fusion
      of this promoter to the beta-gal gene of pAK80 revealed that expression from Pimm
      is significantly reduced in the presence of LtnR. Thus, we have demonstrated that
      lacticin 3147 uses a regulatory mechanism not previously identified in
      lantibiotic systems.

PMID- 11251819
TI  - The cold-shock stress response in Mycobacterium smegmatis induces the expression
      of a histone-like protein.
AB  - The response of Mycobacterium smegmatis to a cold shock was investigated by
      monitoring changes in both growth and cellular protein composition of the
      organism. The nature of the cellular response was influenced by the magnitude of
      the temperature reduction, with the shock from 37 degrees C to 10 degrees C
      having the most widespread effect on growth, metabolism and protein composition.
      This 27 degrees C temperature reduction was associated with a lag period of 21-24
      h before increases were seen in all the measured cellular activities. The
      response to cold shock was adaptive, with growth resuming after this period,
      albeit at a 50-fold slower rate. The synthesis of at least 15 proteins was
      induced during the lag period. Two distinct patterns of cold-induced synthesis
      were apparent, namely transient and continuous, indicating the production of both
      cold-induced and cold-acclimation proteins. One of these cold-shock proteins,
      CipMa, was identified as the histone-like protein, Hlp, of M. smegmatis, which is
      also induced during anaerobic-induced dormancy. The corresponding gene
      demonstrated transient, cold-inducible expression with a five- to sevenfold
      increase in mRNA occurring 9-12 h after temperature shift. Although bacterial
      survival was unaffected, CipMa/Hlp knock-out mutants were unable to adapt
      metabolically to the cold shock and resume growth, thus indicating a key role for
      CipMa in the cold-shock response.

PMID- 11251820
TI  - Analysis of the replicon region and identification of an rRNA operon on pBM400 of
      Bacillus megaterium QM B1551.
AB  - An 18 633 bp region containing the replicon from the approximately 53 kb pBM400
      plasmid of Bacillus megaterium QM B1551 has been sequenced and characterized.
      This region contained a complete rRNA operon plus 10 other potential open reading
      frames (ORFs). The replicon consisted of an upstream promoter and three
      contiguous genes (repM400, orfB and orfC) that could encode putative proteins of
      428, 251 and 289 amino acids respectively. A 1.6 kb minimal replicon was defined
      and contained most of repM400. OrfB was shown to be required for stability. Three
      12 bp identical tandem repeats were located within the coding region of repM400,
      and their presence on another plasmid caused incompatibility with their own
      cognate replicon. Nonsense, frameshift and deletion mutations in repM400
      prevented replication, but each mutation could be complemented in trans. RepM400
      had no significant similarity to sequences in the GenBank database, whereas five
      other ORFs had some similarity to gene products from other plasmids and the
      Bacillus genome. An rRNA operon was located upstream of the replication region
      and is the first rRNA operon to be sequenced from B. megaterium. Its unusual
      location on non-essential plasmid DNA has implications for systematics and
      evolutionary biology.

PMID- 11251821
TI  - Osmotic stress causes a G1 cell cycle delay and downregulation of Cln3/Cdc28
      activity in Saccharomyces cerevisiae.
AB  - Moderate hyperosmotic stress on Saccharomyces cerevisiae cells produces a
      temporary delay at the G1 stage of the cell cycle. This is accompanied by
      transitory downregulation of CLN1, CLN2 and CLB5 transcript levels, although not
      of CLN3, which codes for the most upstream activator of the G1/S transition.
      Osmotic shock to cells synchronized in early G1, when Cln3 is the only cyclin
      present, causes a delay in cell cycle resumption. This points to Cln3 as being a
      key cell cycle target for osmotic stress. We have observed that osmotic shock
      causes downregulation of the kinase activity of Cln3-Cdc28 complexes. This is
      concomitant with a temporary accumulation of Cln3 protein as a result of
      increased stability. The effects of the osmotic stress in G1 are not suppressed
      in CLN3-1 cells with increased kinase activity, as the Cln3-Cdc28 activity in
      this mutant is still affected by the shock. Although Hog1 is not required for the
      observed cell cycle arrest in hyperosmotic conditions, it is necessary to resume
      the cell cycle at KCl concentrations higher than 0.4 M.

PMID- 11251822
TI  - Mutational analysis of RsrA, a zinc-binding anti-sigma factor with a thiol
      disulphide redox switch.
AB  - In the Gram-positive bacterium, Streptomyces coelicolor A3(2), expression of the
      thioredoxin system is modulated by a sigma factor called sigmaR in response to
      changes in the cytoplasmic thiol-disulphide status, and the activity of sigmaR is
      controlled post-translationally by an anti-sigma factor, RsrA. In vitro, the anti
      sigma factor activity of RsrA, which contains seven cysteines, correlates with
      its thiol-disulphide redox status. Here, we investigate the function of RsrA in
      vivo. A constructed rsrA null mutant had very high constitutive levels of
      disulphide reductase activity and sigmaR-dependent transcription, confirming that
      RsrA is a negative regulator of sigmaR and a key sensor of thiol-disulphide
      status. Targeted mutagenesis revealed that three of the seven cysteines in RsrA
      (C11, C41 and C44) were essential for anti-sigma factor activity and that a
      mutant RsrA protein containing only these three cysteines was active and still
      redox sensitive in vivo. We also show that RsrA is a metalloprotein, containing
      near-stoichiometric amounts of zinc. On the basis of these data, we propose that
      a thiol-disulphide redox switch is formed between two of C11, C41 and C44, and
      that all three residues play an essential role in anti-sigma factor activity in
      their reduced state, perhaps by acting as ligands for zinc. Unexpectedly, rsrA
      null mutants were blocked in sporulation, probably as a consequence of an
      increase in the level of free sigmaR.

PMID- 11251823
TI  - Non-growing Escherichia coli cells starved for glucose or phosphate use different
      mechanisms to survive oxidative stress.
AB  - Recent data suggest that superoxide dismutases are important in preventing lethal
      oxidative damage of proteins in Escherichia coli cells incubated under aerobic,
      carbon starvation conditions. Here, we show that the alkylhydroperoxide reductase
      AhpCF (AHP) is specifically required to protect cells incubated under aerobic,
      phosphate (Pi) starvation conditions. Additional loss of the HP-I (KatG)
      hydroperoxidase activity dramatically accelerated the death rate of AHP-deficient
      cells. Investigation of the composition of spent culture media indicates that
      DeltaahpCF katG cells leak nutrients, which suggests that membrane lipids are the
      principal target of peroxides produced in Pi-starved cells. In fact, the
      introduction of various mutations inactivating repair activities revealed no
      obvious role for protein or DNA lesions in the viability of ahp cells. Because
      the death of ahp cells was directly related to ongoing aerobic glucose
      metabolism, we wondered how glycolysis, which requires free Pi, could proceed.
      31P nuclear magnetic resonance spectra showed that Pi-starved cells consumed Pi
      but were apparently able to liberate Pi from phosphorylated products, notably
      through the synthesis of UDP-glucose. Whereas expression of the ahpCF and katG
      genes is enhanced in an OxyR-dependent manner in response to H2O2 challenge, we
      found that the inactivation of oxyR and both oxyR and rpoS genes had little
      effect on the viability of Pi-starved cells. In stark contrast, the inactivation
      of both oxyR and rpoS genes dramatically decreased the viability of glucose
      starved cells.

PMID- 11251824
TI  - Evidence for non-enzymatic glycosylation in Escherichia coli.
AB  - Non-enzymatic glycosylation (glycation) is a chain of chemical reactions
      affecting free amino groups in proteins of long-living eukaryotes. It proceeds in
      several steps leading to the consecutive formation of Schiff bases, Amadori
      products and advanced glycation end-products (AGEs). To our knowledge, this
      process has not been observed in prokaryotes so far. However, the present study
      provides clear-cut evidence that glycation takes place in bacteria despite their
      short life span. We have detected AGEs in recombinant human interferon gamma
      (rhIFN-gamma) produced in Escherichia coli as well as in total protein of the
      same bacterium using three different approaches: (i) Western blotting using two
      monoclonal antibodies raised against AGEs; (ii) fluorescent spectroscopy; and
      (iii) investigation of the effect of known AGE inhibitors (such as acetyl
      salicylic acid and thiamine) on the glycation reaction. Our study shows that non
      enzymatic glycosylation is initiated during the normal growth of E. coli and
      results in AGE formation even after isolation of proteins. This process seems to
      be tightly associated with some post-translational modifications observed in the
      cysteineless rhIFN-gamma, such as covalent dimerization and truncation.

PMID- 11251825
TI  - The Escherichia coli histone-like protein HU regulates rpoS translation.
AB  - Escherichia coli HU protein is a major component of the bacterial nucleoid. HU
      stabilizes higher order nucleoprotein complexes and belongs to a family of DNA
      architectural proteins. Here, we report that HU is required for efficient
      expression of the sigma S subunit of RNA polymerase. This rpoS-encoded
      alternative sigmaS factor induces a number of genes implicated in cell survival
      in stationary phase and in multiple stress resistance. By analysis of rpoS-lacZ
      fusions and by pulse-chase experiments, we show that the efficiency of rpoS
      translation is reduced in cells lacking HU, whereas neither rpoS transcription
      nor protein stability is affected by HU. Gel mobility shift assays show that HU
      is able to bind specifically an RNA fragment containing the translational
      initiation region of rpoS mRNA 1000-fold more strongly than double-stranded DNA.
      Together with the in vivo data, this finding strongly suggests that, by binding
      to rpoS mRNA, HU directly stimulates rpoS translation. We demonstrate here that
      HU, an abundant DNA-binding, histone-like protein, is able specifically to
      recognize an RNA molecule and therefore play a role in post-transcriptional
      regulation.

PMID- 11251826
TI  - Blue light adaptation and desensitization of light signal transduction in
      Neurospora crassa.
AB  - The ascomycete Neurospora crassa has the capacity of adapting to a given light
      quantity, leading to transient blue light responses under continuous light
      conditions. Here, we present an investigation of this photoadaptation phenomenon.
      We demonstrated previously that two proteins of the Neurospora blue light signal
      transduction chain, WC1 and WC2, are subject to light-dependent phosphorylation.
      WC1 was phosphorylated in parallel with the transient increase in transcript
      levels of light-regulated genes. Using the light-dependent phosphorylation of WC1
      as a marker for an active signalling state of WC1, we show that the transiency of
      Neurospora blue light responses results from desensitization of the photoreceptor
      and/or the signalling cascade. Furthermore, a Neurospora mutant was characterized
      that revealed a specific defect in photoadaptation. In this mutant, the transient
      expression of light-regulated genes under continuous light, the temporary
      insensitivity after a light pulse and the capability of differentiating between
      and adapting to low and high light intensities were abolished. The corresponding
      protein seems to represent a central component of a negative feedback
      desensitization mechanism. This negative feedback regulation requires continuous
      and light-dependent protein de novo biosynthesis.

PMID- 11251827
TI  - Two atypical mobilization proteins are involved in plasmid CloDF13 relaxation.
AB  - The mobilization region of plasmid CloDF13 was localized to a 3.6 kb DNA segment
      that was analysed by transposon mutagenesis and DNA sequencing. Analysis of the
      DNA sequence allowed us to identify two mobilization genes and the CloDF13 origin
      of conjugative transfer (oriT), which was localized to a 661 bp segment at one
      end of the mobilization (Mob) region. Thus, the overall organization was oriT
      mobB-mobC. Plasmid CloDF13 DNA was isolated mainly as a relaxed form that
      contained a unique strand and site-specific cleavage site (nic). The position of
      nic was mapped to the sequence 5'-GGGTG/GTCGGG-3' by primer extension and
      sequencing reactions. Analysis of Mob- insertion mutants showed that mobC was
      essential for CloDF13 relaxation in vivo. The sequence of mobC predicts a protein
      (MobC) of 243 amino acids without significant similarity to previously reported
      relaxases. In addition to MobC, the product of mobB was also required for CloDF13
      mobilization and for oriT relaxation in vivo. mobB codes for a protein (MobB) of
      653 amino acids with three predicted transmembrane segments at the N-terminus and
      the NTP-binding motifs characteristic of the TraG family of conjugative coupling
      proteins. Membership of the TraG family was confirmed by the fact that CloDF13
      mobilization by plasmid R388 was independent of TrwB and only required PILW.
      However, contrary to the activities found for other coupling proteins, MobB was
      required for efficient oriT cleavage in vivo, suggesting an additional role for
      this particular protein during oriT processing for mobilization. Additionally,
      the cleavage site produced by the joint activities of MobB and MobC was shown to
      contain unblocked ends, suggesting that no stable covalent intermediates between
      relaxase and DNA were formed during the nic cleavage reaction. This is the first
      report of a conjugative transfer system in which nic cleavage results in a free
      nicked-DNA intermediate.

PMID- 11251828
TI  - Global and cognate regulators control the expression of the organic solvent
      efflux pumps TtgABC and TtgDEF of Pseudomonas putida.
AB  - Pseudomonas putida DOT-T1E grows on a water-toluene double liquid phase. Toluene
      tolerance in this microorganism is mainly achieved by at least two efflux pumps
      that belong to the RND family. The TtgDEF efflux pump is induced by toluene,
      whereas the other efflux pump, called TtgABC, is expressed at a high level in
      cells not exposed to toluene and at a lower level in cells grown with toluene.
      The ttgR gene is adjacent to the ttgABC operon and is transcribed divergently
      from ttgA. The expression level of ttgR was fourfold higher in cells growing in
      the presence of toluene than in its absence. In a TtgR-deficient background,
      expression from the ttgA promoter increased about 20-fold, suggesting that TtgR
      represses expression from the ttgA promoter. In this mutant, background
      expression of the ttgR gene was also much higher than in the wild-type
      background; however, its level of expression increased in the presence of
      toluene. In a ttgR mutant background, expression from the ttgD promoter followed
      the same pattern of expression as in the wild type. Analysis of a P. putida
      pTn5cat mutant that exhibited increased sensitivity to a sudden toluene shock,
      regardless of whether or not it was previously exposed to low toluene
      concentrations, revealed that pTn5cat had interrupted an lrp-like gene. The ttgR
      gene was expressed at very high levels in this mutant, with concomitant
      repression of expression of the ttgABC operon. The second ttgDEF efflux pump was
      expressed at low levels in this mutant strain, suggesting that the Lrp-like
      protein is a global regulatory protein involved in the solvent-tolerant response
      of this strain.

PMID- 11251829
TI  - The effects of DNA supercoiling on the expression of operons of the ilv regulon
      of Escherichia coli suggest a physiological rationale for divergently transcribed
      operons.
AB  - Transcriptional activities of closely spaced divergent promoters are affected by
      the accumulation of local negative superhelicity in the region between
      transcribing RNA polymerase molecules (transcriptional coupling). The effect of
      this transcription-induced DNA supercoiling on these promoters depends on their
      intrinsic properties. As the global superhelical density of the chromosome is
      controlled by the energy charge of the cell, which is affected by environmental
      stresses and transitions from one growth state to another, the transcriptional
      coupling that occurs between divergently transcribed promoters is likely to serve
      a physiological purpose. Here, we suggest that transcriptional coupling between
      the divergent promoters of the ilvYC operon of Escherichia coli serves to co
      ordinate the expression of this operon with other operons of the ilv regulon
      during metabolic adjustments associated with growth state transitions. As DNA
      supercoiling-dependent transcriptional coupling between the promoters of other
      divergently transcribed operons is investigated, additional global gene
      regulatory mechanisms and physiological roles are sure to emerge.

PMID- 11251830
TI  - Generalized approach to the regulation and integration of gene expression.
AB  - The volume of electron flow through the cbb3 branch of the electron transport
      chain and the redox state of the quinone pool generate signals that regulate
      photosynthesis gene expression in Rhodobacter sphaeroides. An inhibitory signal
      is generated at the level of the catalytic subunit of the cbb3 cytochrome c
      oxidase and is transduced through the membrane-localized PrrC polypeptide to the
      PrrBA two-component activation system, which controls the expression of most of
      the photosynthesis genes in response to O2. The redox state of the quinone pool
      is monitored by the redox-active AppA antirepressor protein, which determines the
      functional state of the PpsR repressor protein. The antirepressor/repressor
      system as well as a modulator of AppA function, TspO, together with FnrL and PrrA
      stringently control photopigment gene expression. These regulatory elements,
      together with spectral complex-specific assembly factors, control the ultimate
      cellular levels and composition of the photosynthetic membrane.

PMID- 11251832
TI  - A MAP kinase of the vascular wilt fungus Fusarium oxysporum is essential for root
      penetration and pathogenesis.
AB  - The soil-borne vascular wilt fungus Fusarium oxysporum infects a wide variety of
      plant species by directly penetrating roots, invading the cortex and colonizing
      the vascular tissue. We have identified fmk1, encoding a mitogen-activated
      protein kinase (MAPK) of F. oxysporum that belongs to the yeast and fungal
      extracellular signal-regulated kinase (YERK1) subfamily. Targeted mutants of F.
      oxysporum f. sp. lycopersici carrying an inactivated copy of fmk1 have lost
      pathogenicity on tomato plants but show normal vegetative growth and conidiation
      in culture. Colonies of the fmk1 mutants are easily wettable, and hyphae are
      impaired in breaching the liquid-air interface, suggesting defects in surface
      hydrophobicity. Fmk1 mutants also show reduced invasive growth on tomato fruit
      tissue and drastically reduced transcript levels of pl1 encoding the cell wall
      degrading enzyme pectate lyase. Conidia of the mutants germinating in the tomato
      rhizosphere fail to differentiate penetration hyphae, resulting in greatly
      impaired root attachment. The orthologous MAPK gene Pmk1 from the rice leaf
      pathogen Magnaporthe grisea complements invasive growth and partially restores
      surface hydrophobicity, root attachment and pathogenicity in an fmk1 mutant.
      These results demonstrate that FMK1 controls several key steps in the
      pathogenesis of F. oxysporum and suggest a fundamentally conserved role for the
      corresponding MAPK pathway in soil-borne and foliar plant pathogens.

PMID- 11251831
TI  - Identification of a PEST-like motif in listeriolysin O required for phagosomal
      escape and for virulence in Listeria monocytogenes.
AB  - The hly-encoded listeriolysin O (LLO) is a major virulence factor secreted by the
      intracellular pathogen Listeria monocytogenes, which plays a crucial role in the
      escape of bacteria from the phagosomal compartment. Here, we identify a putative
      PEST sequence close to the N-terminus of LLO and focus on the role of this motif
      in the biological activities of LLO. Two LLO variants were constructed: a
      deletion mutant protein, lacking the 19 residues comprising this sequence
      (residues 32-50), and a recombinant protein of wild-type size, in which all the
      P, E, S or T residues within this motif have been substituted. The two mutant
      proteins were fully haemolytic and were secreted in culture supernatants of L.
      monocytogenes in quantities comparable with that of the wild-type protein.
      Strikingly, both mutants failed to restore virulence to a hly-negative strain in
      vivo. In vitro assays showed that L. monocytogenes expressing the LLO deletion
      mutant was strongly impaired in its ability to escape from the phagosomal vacuole
      and, subsequently, to divide in the cytosol of infected cells. This work reveals
      for the first time that the N-terminal portion of LLO plays an important role in
      the development of the infectious process of L. monocytogenes.

PMID- 11251834
TI  - Aged mother cells of Saccharomyces cerevisiae show markers of oxidative stress
      and apoptosis.
AB  - Recently, we and others have shown that genetic and environmental changes that
      increase the load of yeast cells with reactive oxygen species (ROS) lead to a
      shortening of the life span of yeast mother cells. Deletions of yeast genes
      coding for the superoxide dismutases or the catalases, as well as changes in
      atmospheric oxygen concentration, considerably shortened the life span. The
      presence of the physiological antioxidant glutathione, on the other hand,
      increased the life span of yeast cells. Taken together, these results pointed to
      a role for oxygen in the yeast ageing process. Here, we show by staining with
      dihydrorhodamine that old yeast mother cells isolated by elutriation, but not
      young cells, contain ROS that are localized in the mitochondria. A relatively
      large proportion of the old mother cells shows phenotypic markers of yeast
      apoptosis, i.e. TUNEL (TdT-mediated dUTP nick end labelling) and annexin V
      staining. Although it has been shown previously that apoptosis in yeast can be
      induced by a cdc48 allele, by expressing pro-apoptotic human cDNAs or by
      stressing the cells with hydrogen peroxide, we are now showing a physiological
      role for apoptosis in unstressed but aged wild-type yeast mother cells.

PMID- 11251833
TI  - What makes an Escherichia coli promoter sigma(S) dependent? Role of the -13/-14
      nucleotide promoter positions and region 2.5 of sigma(S).
AB  - The sigmaS and sigma70 subunits of Escherichia coli RNA polymerase recognize very
      similar promoter sequences. Therefore, many promoters can be activated by both
      holoenzymes in vitro. The same promoters, however, often exhibit distinct sigma
      factor selectivity in vivo. It has been shown that high salt conditions, reduced
      negative supercoiling and the formation of complex nucleoprotein structures in a
      promoter region can contribute to or even generate sigmaS selectivity. Here, we
      characterize the first positively acting sigmaS-selective feature in the promoter
      sequence itself. Using the sigmaS-dependent csiD promoter as a model system, we
      demonstrate that C and T at the -13 and -14 positions, respectively, result in
      strongest expression. We provide allele-specific suppression data indicating that
      these nucleotides are contacted by K173 in region 2.5 of sigmaS. In contrast,
      sigma70, which features a glutamate at the corresponding position (E458), as well
      as the sigmaS(K173E) variant, exhibit a preference for a G(-13). C(-13) is highly
      conserved in sigmaS-dependent promoters, and additional data with the osmY
      promoter demonstrate that the K173/C(-13) interaction is of general importance.
      In conclusion, our data demonstrate an important role for region 2.5 in sigmaS in
      transcription initiation. Moreover, we propose a consensus sequence for a sigmaS
      selective promoter and discuss its emergence and functional properties from an
      evolutionary point of view.

PMID- 11251836
TI  - Phosphatidylcholine levels in Bradyrhizobium japonicum membranes are critical for
      an efficient symbiosis with the soybean host plant.
AB  - Phosphatidylcholine (PC), the major membrane phospholipid in eukaryotes, is found
      in only some bacteria including members of the family Rhizobiaceae. For this
      reason, it has long been speculated that rhizobial PC might be required for a
      successful interaction of rhizobia with their legume host plants in order to
      allow the formation of nitrogen-fixing root nodules. A major pathway for PC
      formation in prokaryotes involves a threefold methylation of the precursor
      phosphatidylethanolamine (PE). Here, we report on the isolation of a
      Bradyrhizobium japonicum gene (pmtA) encoding the phospholipid N
      methyltransferase PmtA. Upon expression of the bradyrhizobial pmtA gene in
      Escherichia coli, predominantly monomethylphosphatidylethanolamine was formed
      from PE. PmtA-deficient B. japonicum mutants still produced low levels of PC by a
      second methylation pathway. The amount of PC formed in such mutants (6% of total
      phospholipids) was greatly decreased compared with the wild type (52% of total
      phospholipids). Root nodules of soybean plants infected with B. japonicum pmtA
      mutants showed a nitrogen fixation activity of only 18% of the wild-type level.
      The interior colour of the nodules was beige instead of red, suggesting decreased
      amounts of leghaemoglobin. Moreover, ultrastructure analysis of these nodules
      demonstrated a greatly reduced number of bacteroids within infected plant cells.
      These data suggest that the biosynthesis of wild-type amounts of PC are required
      to allow for an efficient symbiotic interaction of B. japonicum with its soybean
      host plant.

PMID- 11251835
TI  - Mycobacterial FurA is a negative regulator of catalase-peroxidase gene katG.
AB  - In several bacteria, the catalase-peroxidase gene katG is under positive control
      by oxyR, a transcriptional regulator of the peroxide stress response. The
      Mycobacterium tuberculosis genome also contains sequences corresponding to oxyR,
      but this gene has been inactivated in the tubercle bacillus because of the
      presence of multiple mutations and deletions. Thus, M. tuberculosis katG and
      possibly other parts of the oxidative stress response in this organism are either
      not regulated or are controlled by a factor different from OxyR. The
      mycobacterial FurA is a homologue of the ferric uptake regulator Fur and is
      encoded by a gene located immediately upstream of katG. Here, we examine the
      possibility that FurA regulates katG expression. Inactivation of furA on the
      Mycobacterium smegmatis chromosome, a mycobacterial species that also lacks an
      oxyR homologue, resulted in derepression of katG, concomitant with increased
      resistance of the furA mutant to H2O2. In addition, M. smegmatis furA::Km(r) was
      more sensitive to the front-line antituberculosis agent isonicotinic acid
      hydrazide (INH) compared with the parental furA+ strain. The phenotypic
      manifestations were specific, as the mutant strain did not show altered
      sensitivity to organic peroxides, and both H2O2 and INH susceptibility profiles
      were complemented by the wild-type furA+ gene. We conclude that FurA is a second
      regulator of oxidative stress response in mycobacteria and that it negatively
      controls katG. In species lacking a functional oxyR, such as M. tuberculosis and
      M. smegmatis, FurA appears to be a dominant regulator affecting mycobacterial
      physiology and intracellular survival.

PMID- 11251837
TI  - Anaerobic acquisition of [4FE 4S] clusters by the inactive FNR(C20S) variant and
      restoration of activity by second-site amino acid substitutions.
AB  - The FNR protein of Escherichia coli controls the transcription of target genes in
      response to anoxia. The anaerobic incorporation of oxygen-sensitive [4Fe 4S]
      clusters promotes dimerization, which in turn enhances DNA binding. Four
      potential iron ligands (C20, C23, C29 and C122) are essential for normal FNR
      activity in vivo. Three FNR variants (C20S, C23G and C29G) retained the ability
      to incorporate oxygen-sensitive [4Fe 4S] clusters and to bind target DNA with
      essentially unimpaired affinity, suggesting that their failure to function
      normally in vivo resides at a later stage in the signal transduction pathway. The
      C122 variant failed to assemble iron-sulphur clusters and to bind DNA. Second
      site substitutions that partially restore activity to FNR(C20S) were generated by
      error-prone polymerase chain reaction and were located in the dimer interface, in
      the activating regions (AR1, 2 or 3) or close to C122. Substitutions at E47, R48,
      E123, I124, E127 or T128 allowed the extent of the FNR AR2 surface to be defined.
      Only one revertant, FNR(C20S Y69F G149S), specifically corrected the C20S defect.
      It was concluded that [4Fe 4S] cluster acquisition, dimerization and DNA binding
      are not sufficient to confer transcription regulatory activity on FNR: the iron
      sulphur cluster must also be correctly liganded in order to establish effective
      activating contacts between FNR and RNA polymerase.

PMID- 11251838
TI  - The autolysin Ami contributes to the adhesion of Listeria monocytogenes to
      eukaryotic cells via its cell wall anchor.
AB  - Adherence of pathogenic microorganisms to the cell surface is a key event during
      infection. We have previously reported the characterization of Listeria
      monocytogenes transposon mutants defective in adhesion to eukaryotic cells. One
      of these mutants had lost the ability to produce Ami, a 102 kDa autolytic amidase
      with an N-terminal catalytic domain and a C-terminal cell wall-anchoring domain
      made up of repeated modules containing the dipeptide GW ('GW modules'). We
      generated ami null mutations by plasmid insertion into L. monocytogenes strains
      lacking the invasion proteins InlA (EGDDeltainlA), InlB (EGDDeltainlB) or both
      (EGDDeltainlAB). These mutants were 5-10 times less adherent than their parental
      strains in various cell types. The adhesion capacity of the mutants was restored
      by complementation with a DNA fragment encoding the Ami cell wall-anchoring
      domain fused to the Ami signal peptide. The cell-binding activity of the Ami cell
      wall-anchoring domain was further demonstrated using the purified polypeptide.
      Growth of the ami null mutants constructed in EGD and EGDDeltainlAB backgrounds
      was attenuated in the livers of mice inoculated intravenously, indicating a role
      for Ami in L. monocytogenes virulence. Adhesive properties have recently been
      reported in the non-catalytic domain of two other autolysins, Staphylococcus
      epidermidis AtlE and Staphylococcus saprophyticus Aas. Interestingly, we found
      that these domains were also composed of repeated GW modules. Thus, certain
      autolysins appear to promote bacterial attachment by means of their GW repeat
      domains. These molecules may contribute to the colonization of host tissues by
      Gram-positive bacteria.

PMID- 11251839
TI  - JlpA, a novel surface-exposed lipoprotein specific to Campylobacter jejuni,
      mediates adherence to host epithelial cells.
AB  - A 1116 bp open reading frame (ORF), designated jlpA, encoding a novel species
      specific lipoprotein of Campylobacter jejuni TGH9011, was identified from
      recombinant plasmid pHIP-O. The jlpA gene encodes a polypeptide (JlpA) of 372
      amino acid residues with a molecular mass of 42.3 kDa. JlpA contains a typical
      signal peptide and lipoprotein processing site at the N-terminus. The presence of
      a lipid moiety on the JlpA molecule was confirmed by the incorporation of [3H]
      palmitic acid. Immunoblotting analysis of cell surface extracts prepared using
      glycine-acid buffer (pH 2.2) and proteinase K digestion of whole cells indicated
      that JlpA is a surface-exposed lipoprotein in C. jejuni. JlpA is loosely
      associated with the cell surface, as it is easily extracted from the C. jejuni
      outer membrane by detergents, such as sarcosyl and Triton X-100. JlpA is released
      to the culture medium, and its concentration increases in a time-dependent
      fashion. The adherence of both insertion and deletion mutants of jlpA to HEp-2
      epithelial cells was reduced compared with that of parental C. jejuni TGH9011.
      Adherence of C. jejuni to HEp-2 cells was inhibited in a dose-dependent manner
      when the bacterium was preincubated with anti-GST-JlpA antibodies or when HEp-2
      cells were preincubated with JlpA protein. A ligand-binding immunoblotting assay
      showed that JlpA binds to HEp-2 cells, which suggests that JlpA is C. jejuni
      adhesin.

PMID- 11251840
TI  - Three-component-mediated serotype conversion in Pseudomonas aeruginosa by
      bacteriophage D3.
AB  - Bacteriophage D3 is capable of lysogenizing Pseudomonas aeruginosa PAO1 (serotype
      O5), converting the O-antigen from O5 to O16 and O-acetylating the N
      acetylfucosamine moiety. To investigate the mechanism of lysogenic conversion, a
      3.6 kb fragment from the D3 genome was isolated capable of mediating serotypic
      conversion identical to the D3 lysogen strain (AK1380). The PAO1 transformants
      containing this 3.6 kb of D3 DNA exhibited identical lipopolysaccharide (LPS)
      banding patterns to serotype O16 in silver-stained SDS-PAGE gels and displayed
      reactivity to an antibody specific for O-acetyl groups. Further analysis led to
      the identification of three open reading frames (ORFs) required for serotype
      conversion: an alpha-polymerase inhibitor (iap); an O-acetylase (oac); and a beta
      polymerase (wzybeta). The alpha-polymerase inhibitor (Iap) is capable of
      inhibiting the assembly of the serotype-specific O5 B-band LPS and allows the
      phage-encoded beta-polymerase (Wzybeta) to form new beta-linked B-band LPS. The
      D3 phage also alters the LPS by the addition of O-acetyl groups to the FucNAc
      residue in the O-antigen repeat unit by the action of the D3 O-acetylase (Oac).
      These three components form a simple yet elegant system by which bacteriophage D3
      is capable of altering the surface of P. aeruginosa PAO1.

PMID- 11251841
TI  - Replication mutations differentially enhance RecA-dependent and RecA-independent
      recombination between tandem repeats in Bacillus subtilis.
AB  - We have studied DNA recombination between 513 bp tandem direct repeats present in
      a kanamycin resistance gene inserted in the Bacillus subtilis chromosome. Tandem
      repeat deletion was not significantly affected by a recA mutation. However,
      recombination was stimulated by mutations in genes encoding replication proteins,
      including the primosomal proteins DnaB, DnaD and the DnaG primase, the putative
      DNA polymerase III subunits PolC, DnaN and DnaX, as well as the DNA polymerase
      DnaE. Hyper-recombination was found to be dependent on RecA in the dnaE, dnaN and
      dnaX mutants, whereas the dnaG and dnaD mutants stimulated recombination
      independently of RecA. Altogether, these data show that both RecA-dependent and
      RecA-independent mechanisms contribute to recombination between tandem repeats in
      B. subtilis and that both types of recombination are stimulated by replication
      mutations.

PMID- 11251842
TI  - Chromosomal insertion and excision of a 30 kb unstable genetic element is
      responsible for phase variation of lipopolysaccharide and other virulence
      determinants in Legionella pneumophila.
AB  - We recently described the phase-variable expression of a virulence-associated
      lipopolysaccharide (LPS) epitope in Legionella pneumophila. In this study, the
      molecular mechanism for phase variation was investigated. We identified a 30 kb
      unstable genetic element as the molecular origin for LPS phase variation. Thirty
      putative genes were encoded on the 30 kb sequence, organized in two putative
      opposite transcription units. Some of the open reading frames (ORFs) shared
      homologies with bacteriophage genes, suggesting that the 30 kb element was of
      phage origin. In the virulent wild-type strain, the 30 kb element was located on
      the chromosome, whereas excision from the chromosome and replication as a high
      copy plasmid resulted in the mutant phenotype, which is characterized by
      alteration of an LPS epitope and loss of virulence. Mapping and sequencing of the
      insertion site in the genome revealed that the chromosomal attachment site was
      located in an intergenic region flanked by genes of unknown function. As phage
      release could not be induced by mitomycin C, it is conceivable that the 30 kb
      element is a non-functional phage remnant. The protein encoded by ORF T on the 30
      kb plasmid could be isolated by an outer membrane preparation, indicating that
      the genes encoded on the 30 kb element are expressed in the mutant phenotype.
      Therefore, it is conceivable that the phenotypic alterations seen in the mutant
      depend on high-copy replication of the 30 kb element and expression of the
      encoded genes. Excision of the 30 kb element from the chromosome was found to
      occur in a RecA-independent pathway, presumably by the involvement of RecE, RecT
      and RusA homologues that are encoded on the 30 kb element.

PMID- 11251844
TI  - A novel mechanism controls anaerobic and catabolite regulation of the Escherichia
      coli tdc operon.
AB  - The tdc operon is subject to CRP-controlled catabolite repression. Expression of
      the operon is also induced anaerobically, although this regulation does not rely
      on direct control by either FNR or ArcA. Recently, the anaerobic expression of
      the tdc operon was found to be fortuitously induced in the presence of glucose by
      a heterologous gene isolated from the Gram-positive anaerobe Clostridium
      butyricum. The gene, termed tcbC, encoded a histone-like protein of 14.5 kDa.
      Using tdc-lacZ fusions, it was shown that TcbC did not activate tdc expression by
      functionally replacing any of the operon regulators. In vitro transcription
      analyses with RNA polymerase and CRP revealed that faithful CRP-dependent
      transcription initiation occurred only on supercoiled templates. No specific, CRP
      dependent transcription initiation was observed on relaxed or linear DNA
      templates. Surprisingly, purified His-tagged TcbC activated transcription from a
      relaxed, circular template, but not from supercoiled or linear templates.
      Examination of the CRP binding site of the tdc promoter revealed that it was
      located 43.5 bp upstream of the transcription initiation site. Repositioning of
      the CRP site at -41.5 bp abolished activation by the TcbC protein and allowed CRP
      dependent transcription to occur on linear, relaxed and supercoiled templates.
      TcbC bound DNA non-specifically; however, in topoisomerase I relaxation assays,
      it was demonstrated that TcbC imposed torsional constraints on negatively
      supercoiled DNA, which influenced the ability of the enzyme to relax the
      topoisomers. Taken together, these results strongly suggest that TcbC activates
      transcription of tdc by altering the local topological status of the tdc promoter
      and that, in the wild-type tdc promoter, the CRP binding site is misaligned to
      allow transcription to occur only under optimal conditions. Indeed, in vivo
      transcription analyses revealed that repositioning of the CRP binding site to 
      41.5 bp resulted in high-level, CRP-dependent transcription, even under
      catabolite-repressing conditions, and that transcription was no longer influenced
      by TcbC. Remarkably, however, anaerobic regulation of the mutant promoter was
      retained. This indicates that the other tdc regulators, TdcA and TdcR, govern
      anaerobic transcription activation by CRP.

PMID- 11251843
TI  - Type 1 pili-mediated adherence of Escherichia coli strain LF82 isolated from
      Crohn's disease is involved in bacterial invasion of intestinal epithelial cells.
AB  - We previously characterized the invasive ability of Escherichia coli strain LF82,
      isolated from an ileal biopsy of a patient with Crohn's disease. In the present
      study, we performed TnphoA insertion mutagenesis to identify genes involved in
      LF82 invasion of intestinal epithelial cells. Most of the non-invasive mutants
      had an insertion mutation within the type 1 pili-encoding operon. Two non
      invasive fim mutants, which harboured an insertion within the fimI and fimF
      genes, still adhered but had lost the ability to induce host cell membrane
      elongations at the sites of contact with the epithelial cells.
      Transcomplementation experiments with a fim operon cloned from E. coli K-12
      restored both invasive ability and the ability to induce host cell membrane
      elongations. Expression of the cloned LF82 or K-12 fim operon into the non
      invasive laboratory strain JM109 did not confer invasive properties. Thus, these
      findings showed that: (i) type 1 pili-mediated adherence is involved in LF82
      induced perturbation of host cell signalling responsible for membrane
      elongations; (ii) native shafts are required for type 1 pilus-mediated induction
      of membrane elongations; (iii) this active phenomenon is a key step in the
      establishment of the invasive process; and (iv) type 1 pili alone are not
      sufficient to trigger bacterial internalization.

PMID- 11251845
TI  - A novel group I intron-encoded endonuclease specific for the anticodon region of
      tRNA(fMet) genes.
AB  - Open reading frames (ORFs) are frequently inserted into group I self-splicing
      introns. These ORFs encode either maturases that are required for splicing of the
      intron or DNA endonucleases that promote intron mobility. A self-splicing intron
      in the tRNA(fMet) gene of Synechocystis PCC 6803, which has been proposed to have
      moved laterally within the cyanobacteria, contains an ORF that is unrelated to
      known intron-encoded endonucleases or maturases. Here, using an in vitro
      transcription-translation system, we show that this intronic ORF encodes a double
      strand DNA endonuclease, I-Ssp6803I. I-Ssp6803I cleaves each strand of the
      intronless tRNA(fMet) gene adjacent to the anticodon triplet leaving 3 bp 3'
      extensions and has no activity at intron-exon boundaries. Using an in vitro
      cleavage assay and scanning deletion mutants of the intronless target site, the
      minimal recognition site was determined to be a partially palindromic 20 bp
      region encompassing the entire anticodon stem and loop of the tRNA(fMet) gene. I
      Ssp6803I represents a novel intron-encoded DNA endonuclease and is the first
      example of a chromosomally encoded group I intron endonuclease in bacteria.

PMID- 11251846
TI  - Dominant-negative mutants of prgX: evidence for a role for PrgX dimerization in
      negative regulation of pheromone-inducible conjugation.
AB  - PrgX negatively regulates prgQ transcriptional readthrough in the pheromone
      inducible enterococcal conjugative plasmid pCF10. We isolated and characterized
      13 dominant-negative prgX mutants, all of which mapped in either the N- or the C
      terminus of PrgX. In all mutants, the in vivo level of Qa RNA, an antisense RNA
      to prgQ RNA, was greatly reduced. When oligomerization of PrgX was tested with a
      phage lambda cI repressor fusion system, the oligomerization domain was found to
      be between amino acid residues 78 and 280. When histidine-tagged PrgX (His-PrgX)
      was purified by nickel column chromatography from a strain also expressing PrgX,
      PrgX was co-purified with His-PrgX. Although PrgX was expressed at a much higher
      level than His-PrgX, an approximately equal amount of PrgX was co-purified.
      Pheromone induction greatly decreased the co-purification of PrgX. Based on these
      data, we propose that both the N- and the C-terminal domains of PrgX are required
      for PrgX positive autoregulation and for the repression of prgQ transcription
      readthrough. In vivo, PrgX exists as a dimer, and dimerization is mediated by the
      central region of PrgX.

PMID- 11251847
TI  - Role of the Bacillus subtilis fatty acid desaturase in membrane adaptation during
      cold shock.
AB  - In our attempt to understand the cold shock response of Bacillus subtilis, we
      report on the role of the B. subtilis fatty acid desaturase (FA-D) Des during
      membrane adaptation to low temperatures and demonstrate its importance during
      cold shock. A des null mutant was constructed and analysed in comparison with its
      parental strain. Growth studies and large-scale comparative fatty acid (FA)
      analysis revealed a severe cold-sensitive phenotype of the des deletion mutant
      during the absence of isoleucine and showed that four unsaturated fatty acid
      (UFA) species differing in length, branching pattern and position of the double
      bond are synthesized in B. subtilis JH642 but not in the des null mutant. Apart
      from the lack of UFA synthesis, the FA-D deletion strain showed a dramatically
      altered saturated fatty acid (SFA) profile at the onset of the stationary growth
      phase in the presence of exogenous isoleucine sources. Expression of des
      integrated in trans at the amyE locus of the des deletion strain not only cured
      the cold-sensitive phenotype observed for the des mutant but allowed much better
      growth than in strain JH642 after a shift from 37 degrees C to 15 degrees C.
      These results show that, during cold shock adaptation, des expression can
      completely replace the isoleucine-dependent, long-term, FA branching adaptation
      mechanism. We conclude that the crucial aspect in cold adaptation of the
      cytoplasmic membrane is not its specific molecular composition but rather its
      physical status in terms of its fluidity.

PMID- 11251849
TI  - Generation and characterization of a PhoP homologue mutant of Neisseria
      meningitidis.
AB  - Two-component regulatory systems are important regulators of virulence genes in a
      number of bacteria. Genes encoding a two-component regulator system, with
      homology to the phoP/phoQ system in salmonella, were identified in the
      meningococcal genome. Allele replacement was used to generate a meningococcal
      knock-out mutant of the regulator component of this system, and its phenotype was
      examined. The mutant displayed many differences in protein profiles compared with
      wild type, consistent with it being a gene-regulatory mutation. Many of the
      growth characteristics of the mutant were similar to those of phoP mutants of
      salmonella: it was unable to grow at low concentrations of magnesium and was
      sensitive to defensins and other environmental stresses. Magnesium-regulated
      differences in protein expression were abrogated in the mutant, indicating that
      the meningococcal PhoP/PhoQ system may, as in salmonella, respond to changes in
      environmental magnesium levels. These results are consistent with the PhoP
      homologue playing a similar role in the meningococcus to PhoP in salmonella and
      suggest that it may similarly be involved in the regulation of virulence genes in
      response to environmental stimuli in the meningococcus. In support of this
      conclusion, we found the mutant grew was unable to grow in mouse serum and was
      attenuated in its ability to traverse through a layer of human epithelial cells.
      Identification of those genes regulated by the meningococcal PhoP may provide a
      route towards the identification of virulence genes in the meningococcus.

PMID- 11251848
TI  - Heterologous transposition in Aspergillus nidulans.
AB  - Aspergillus nidulans is one of the model ascomycete fungi. Transposition events
      have never been described in this organism. We have determined that this organism
      has at least 13 copies of a Fot1-related element. These copies are transcribed,
      non-methylated and polymorphic in various wild isolates. In spite of this, we
      have failed to isolate transposon insertions when the resident niaD gene is used
      as a transposon trap. This contrasts with the situation described previously in
      Fusarium oxysporum. We show that two elements of F. oxysporum, Fot1 and impala,
      transpose efficiently in A. nidulans. We have developed the impala system by
      tagging it with the yA gene. This permits the visual detection of the transposon
      by the colour of the conidiospores. We demonstrate that no endogenous transposase
      of A. nidulans is able to act in trans on a defective impala element, whereas its
      own transposase driven by two different promoters is able to mobilize this
      element. The frequency of excision of these modified elements is between 10(-4)
      and 10(-5). Loss of the transposable element occurs in about 10% of all excision
      events. In the remaining 90%, the transposon seems to be integrated at random
      positions in the genome. The availability of mitochondrially inherited mutations
      has allowed us to demonstrate that hybrid dysgenesis is apparently absent in A.
      nidulans. The development of this system opens the way to investigating the
      mechanism underlying the paucity of transposition events leading to visible
      phenotypes. It should allow us to develop efficient gene-tagging tools, useful in
      this and other fungi.

PMID- 11251850
TI  - Expression of the Bacillus subtilis sulphonate-sulphur utilization genes is
      regulated at the levels of transcription initiation and termination.
AB  - The Bacillus subtilis ssuBACD gene cluster is required for the utilization of
      aliphatic sulphonates as sulphur sources. The regulation of expression of the ssu
      genes was studied in constructs carrying chromosomal transcriptional fusions of
      the ssu promoter region to lacZ. When sulphate or cystine served as sulphur
      sources, expression of the ssu genes was repressed. A putative terminator located
      between the promoter and the start of the ssuB gene partially overlaps a putative
      antiterminator. Removal of both the antiterminator and the terminator led to a
      decrease in the repression ratio of about 10-fold, but not to constitutive
      expression. Replacement of the ssu promoter by the Pspac promoter led to
      decreased expression of the ssu genes, but not to loss of repression by sulphate
      and cystine. Thus, the repression exerted by sulphate and cystine resulted from
      regulation at the level of both transcription initiation and transcription
      termination. O-acetyl-L-serine, a precursor of cysteine, served as effector
      molecule in both regulation systems.

PMID- 11251851
TI  - Catabolite repression mediated by the CcpA protein in Bacillus subtilis: novel
      modes of regulation revealed by whole-genome analyses.
AB  - Previous studies have shown that the CcpA protein of Bacillus subtilis is a major
      transcription factor mediating catabolite repression. We report here whole
      transcriptome analyses that characterize CcpA-dependent, glucose-dependent gene
      expression and correlate the results with full-genome computer analyses of DNA
      binding (CRE) sites for CcpA. The data obtained using traditional approaches show
      good agreement with those obtained using the transcriptome approach. About 10% of
      all genes in B. subtilis are regulated > 3x by glucose, with repressed genes
      outnumbering activated genes three to one. Eighty per cent of these genes depend
      on CcpA for regulation. Classical approaches have provided only evidence for CcpA
      mediated, glucose-dependent activation or repression. We show here that CcpA also
      mediates glucose-independent activation or repression, and that glucose may alter
      either the direction or the intensity of either effect. Computer analyses
      revealed the presence of CRE sites in most operons subject to CcpA-mediated
      glucose repression, but not in those subject to glucose activation, suggesting
      that either secondary transcription factors regulate the latter genes or
      activation by CcpA involves a dissimilar binding site. Operons encoding the
      constituents of ABC-type transporters that are subject to CcpA-mediated glucose
      regulation show two distinct patterns: either all genes in the operon are
      regulated in parallel (the minor class) or the gene encoding the extracytoplasmic
      solute-binding receptor is preferentially regulated (the major class). Genes
      subject to CcpA-independent catabolite repression are primarily concerned with
      sporulation. Several transcription factors were identified that are themselves
      regulated by CcpA at the transcriptional level. Representative data with
      functionally characterized genes are presented to illustrate the novel findings.
      The comprehensive transcriptome data are available on our website:
      www.biology.uesd.edu/~MSAIER/regulation/ and also on http://www.blackwell
      science.com/ products/journals/suppmat/MMI/MMI2328/MMI2328sm.htm

PMID- 11251852
TI  - Regulation of RpoS by a novel small RNA: the characterization of RprA.
AB  - Translational regulation of the stationary phase sigma factor RpoS is mediated by
      the formation of a double-stranded RNA stem-loop structure in the upstream region
      of the rpoS messenger RNA, occluding the translation initiation site. The
      interaction of the rpoS mRNA with a small RNA, DsrA, disrupts the double-strand
      pairing and allows high levels of translation initiation. We screened a multicopy
      library of Escherichia coli DNA fragments for novel activators of RpoS
      translation when DsrA is absent. Clones carrying rprA (RpoS regulator RNA)
      increased the translation of RpoS. The rprA gene encodes a 106 nucleotide
      regulatory RNA. As with DsrA, RprA is predicted to form three stem-loops and is
      highly conserved in Salmonella and Klebsiella species. Thus, at least two small
      RNAs, DsrA and RprA, participate in the positive regulation of RpoS translation.
      Unlike DsrA, RprA does not have an extensive region of complementarity to the
      RpoS leader, leaving its mechanism of action unclear. RprA is non-essential.
      Mutations in the gene interfere with the induction of RpoS after osmotic shock
      when DsrA is absent, demonstrating a physiological role for RprA. The existence
      of two very different small RNA regulators of RpoS translation suggests that such
      additional regulatory RNAs are likely to exist, both for regulation of RpoS and
      for regulation of other important cellular components.

PMID- 11251853
TI  - Expression of the INO2 regulatory gene of Saccharomyces cerevisiae is controlled
      by positive and negative promoter elements and an upstream open reading frame.
AB  - The INO2 gene encodes a transcriptional activator of the phospholipid
      biosynthetic genes of Saccharomyces cerevisiae. Complete derepression of
      phospholipid biosynthetic gene expression in response to inositol/choline
      deprivation requires both INO2 and INO4. Ino2p dimerizes with Ino4p to bind the
      upstream activating sequence (UAS)INO element found in the promoters of the
      target genes. We have demonstrated previously that transcription from the INO2
      promoter is autoregulated 12-fold in a manner identical to that of the target
      genes. Here, we show that this regulation occurs at the levels of transcription
      and translation. Transcription accounts for fourfold regulation, whereas
      translation accounts for an additional threefold regulation. Regulation of
      transcription requires a UAS(INO) element. Additional promoter elements include
      an upstream essential sequence (UES) located upstream of the UAS(INO) element and
      a negative regulatory element in the vicinity of the UAS(INO) element. Regulation
      of translation is dependent on an upstream open reading frame (uORF) in the INO2
      leader. These data support the model that regulatory gene promoters may display
      unusual organizations and may be subject to multiple levels of regulation. We
      have shown previously that the UME6 gene positively regulates INO2 expression.
      Here, we limit the UME6-responsive region of the INO2 promoter to nucleotides 
      217 to -56.

PMID- 11251854
TI  - Natural chaperonin of the hyperthermophilic archaeum, Thermococcus strain KS-1: a
      hetero-oligomeric chaperonin with variable subunit composition.
AB  - To study the difference in expression of the chaperonin alpha- and beta-subunits
      in Thermococcus strain KS-1 (T. KS-1), we measured their intracellular contents
      at various growth temperatures using subunit-specific antibodies. The beta
      subunit was significantly more abundant with increasing temperature (maximum at
      93 degrees C), whereas the alpha-subunit was not. Native PAGE with Western blot
      analysis indicated that the natural chaperonins in the crude extracts of T. KS-1
      cells grown between 65 degrees C and 95 degrees C migrate as single bands with
      different mobility. The recombinant alpha- and beta-subunit homo-oligomers
      migrated differently from each other and from natural chaperonins.
      Immunoprecipitation also showed that the natural chaperonin was the hetero
      oligomer. These results indicate that chaperonin in T. KS-1 formed a hetero
      oligomer with variable subunit composition, and that the beta-subunit may be
      adapted to a higher temperature than the alpha-subunit. T. KS-1 probably changes
      its chaperonin subunit composition to acclimatize to the ambient temperature.

PMID- 11251856
TI  - The new millennium.

PMID- 11251855
TI  - Chs1 of Candida albicans is an essential chitin synthase required for synthesis
      of the septum and for cell integrity.
AB  - CaCHS1 of the fungal pathogen Candida albicans encodes an essential chitin
      synthase that is required for septum formation, viability, cell shape and
      integrity. The CaCHS1 gene was inactivated by first disrupting one allele using
      the ura-blaster protocol, then placing the remaining allele under the control of
      the maltose-inducible, glucose-repressible MRP1 promoter. Under repressing
      conditions, yeast cell growth continued temporarily, but daughter buds failed to
      detach from parents, resulting in septumless chains of cells with constrictions
      defining contiguous compartments. After several generations, a proportion of the
      distal compartments lysed. The conditional Deltachs1 mutant also failed to form
      primary septa in hyphae; after several generations, growth stopped, and hyphae
      developed swollen balloon-like features or lysed at one of a number of sites
      including the hyphal apex and other locations that would not normally be
      associated with septum formation. CHS1 therefore synthesizes the septum of both
      yeast and hyphae and also maintains the integrity of the lateral cell wall. The
      conditional mutant was avirulent under repressing conditions in an experimental
      model of systemic infection. Because this gene is essential in vitro and in vivo
      and is not present in humans, it represents an attractive target for the
      development of antifungal compounds.

PMID- 11251859
TI  - Exposure to a high concentration of mite allergen in early infancy is a risk
      factor for developing atopic dermatitis: a 3-year follow-up study.
AB  - The cause of allergy is multi-factorial, and the development of an allergic
      disease seems to be the result of an interaction between genetic and
      environmental factors. The goal for preventing the development of allergic
      diseases is to avoid sensitization to allergens. The aim of this work was to
      study whether or not exposure to environmental allergens early in infancy would
      influence the occurence of various allergic diseases in later life. On an annual
      basis, a total of 931 healthy newborns were followed-up until they reached 3
      years of age. The occurence of allergic diseases was recorded by trained medical
      students during visits. Measurement of Dermatophagoides pteronyssinus (Der p 1)
      concentration in house dust was performed when each baby was 18 and 36 months
      old. Total and specific immunoglobulin E (IgE) antibodies against Der p 1, cow's
      milk, and egg white were evaluated at birth and at 18 months of age. The
      following results were obtained: at 3 years of age, 10.4% had bronchial asthma
      (BA), 21.4% atopic dermatitis (AD), 7.0% urticaria, and 46.8% had experienced
      wheezing; higher family allergy scores led to a higher incidence of AD
      (p=0.0012); exposure to a mite allergen concentration of 1 microg/g of dust may
      be associated with a higher incidence of AD (p=0.0156); the presence of Der p 1
      IgE antibody at 18 months of age was associated with a higher incidence of BA
      (p=0.0001); and children sensitized to egg whites at 18 months of age had an
      increased risk of developing AD at 3 years of age (p=0.0187). Hence, early
      exposure to mite allergen is a risk factor for the development of atopic
      dermatitis, but seems not to be related to the development of bronchial asthma.
      Early sensitization to egg whites increases the risk of developing AD. The early
      detection of serum Der p 1 IgE antibody is associated with a higher incidence of
      bronchial asthma.

PMID- 11251858
TI  - Atopy among schoolchildren in northern and southern Sweden in relation to pet
      ownership and early life events.
AB  - Studies have suggested a higher prevalence of asthma and allergies in northern,
      as compared to southern, Scandinavia. The aim of this study was to evaluate
      regional differences in atopy in relation to pet ownership and certain early life
      events among schoolchildren (n=2108) aged 10-11 years from Linkoping in southern
      Sweden and Ostersund in northern Sweden. The parents completed a questionnaire,
      comprising questions on home environment, heredity, socio-economic conditions,
      and the core questions on symptoms from the International Study of Asthma and
      Allergies in Childhood. The children were skin-prick tested to eight common
      inhalant allergens. Information on maternal smoking habits, gestational age, and
      anthropometric measures were obtained from the Swedish Medical Birth Registry.
      The prevalence of atopic symptoms and sensitization to pollen were similar in
      Ostersund and in Linkoping. A higher prevalence of sensitization to animal dander
      among children in Ostersund could be linked to a higher occurrence of pets in the
      community. Current cat ownership was related to less sensitivity to cat allergen
      but only in children with an atopic heredity. Ponderal index >30 kg/m3 was
      related to an increased risk of atopic sensitization, both in Linkoping (adjusted
      odds ratio 2.1; 95% confidence interval 1.1-4.0) and in Ostersund (adjusted odds
      ratio 2.0; 95% confidence interval 1.1-3.5). Maternal smoking during pregnancy
      was related to an increased risk of atopic sensitization among children in
      Linkoping, whereas current smoking was associated with a decreased risk of
      sensitization in Ostersund. In conclusion, we demonstrated that a high occurrence
      of pets in the community was associated with sensitization, whereas atopic
      symptoms were essentially unaffected. This study has also suggested an
      association between body size at birth and atopic sensitization at 10-11 years of
      age.

PMID- 11251860
TI  - Beta2-agonist exerts differential effects on the development of cord blood T
      cells but not on peripheral blood T cells.
AB  - Asthma is a chronic inflammatory disease characterized by reversible airway
      obstruction caused by edematous airway lining, thickened mucosal secretions, and
      smooth muscle constriction. Beta2-adrenoceptor agonists are widely used in the
      treatment of bronchial asthma because of their ability to induce relaxation of
      airway smooth muscle. Evidence indicates that desensitization and down-regulation
      of beta-adrenoceptors occurs in long-term beta2-agonist therapy, and these
      medications were thought to cause increased severity of, and mortality in,
      asthma. The purpose of this study was to delineate further the potential adverse
      effects of beta2-agonists on the development of T lymphocytes. T cells isolated
      from umbilical cord blood and adult peripheral blood were cultured in the
      presence of salbutamol. Intracellular staining with fluorescence-labeled
      antibodies was used to differentiate the frequency of type 1 T-helper (Th1) and
      type 2 T-helper (Th2) cells. The results showed a statistically significant
      inverse relationship between the concentration of salbutamol and the ratio of Th1
      over Th2 on cord blood T cells. However, this trend was not observed in adult
      peripheral blood T cells. The data revealed another potential adverse effect in
      which chronic beta2-agonist exposure predisposed differentiation of T lymphocytes
      towards Th2 while that of Th1 was relatively suppressed, especially in cord blood
      T cells. Hence, beta2-agonists, despite their effect in symptomatic rescue in
      asthma, should not be used indiscriminately as long-term therapeutic agents.

PMID- 11251861
TI  - Phenotypic changes of T-lymphocyte subsets induced by interleukin-12 and
      interleukin-15 in umbilical cord vs. adult peripheral blood mononuclear cells.
AB  - The decreased incidence of graft-vs.-host disease found following umbilical cord
      blood (CB) transplantation, and the increased susceptibility of newborns to
      infections, have been attributed, in part, to functional and phenotypic
      immaturity of neonatal T cells. We investigated the phenotypic changes of CB T
      cells induced by two immunoregulary cytokines, interleukin (IL)-12 and IL-15,
      alone or in combination. Adult peripheral blood (APB) mononuclear cells (MNCs)
      were also tested for comparison. Prior to culture, the percentages of CD3+ CD8+,
      CD3+ CD25+, and CD3+ CD56+ cells were significantly lower in CB MNCs than in APB
      MNCs. IL-15, but not IL-12, significantly increased CD3+ CD8+ expression among
      the CB MNCs after 1 week of culture. Combining IL-12 and IL-15, however, resulted
      in decreased CB CD3+ CD8+ expression compared with IL-15 alone. The percentage of
      CD3+ CD25+ cells in CB MNCs spontaneously increased in the absence of cytokines,
      while that of CD3+ CD56+ cells in CB MNCs could not be enhanced with cytokines.
      In contrast, the percentages of CD3+ CD25+ and CD3+ CD56+ cells among the APB
      MNCs could be increased with IL-12, IL-15, and further with IL-12 and IL-15
      combined. Thus, different patterns of T-cell subset changes were demonstrated
      between CB MNCs and APB MNCs in response to IL-12 and/or IL-15. These data may
      serve as a foundation for using cytokine therapy in newborns and children
      receiving CB transplants.

PMID- 11251862
TI  - Eosinophil cationic protein and interleukin-8 levels in bronchial lavage fluid
      from children with asthma and infantile wheeze.
AB  - It has been shown previously that airway eosinophils characterize childhood
      asthma and neutrophils contribute to the pathophysiology of both infantile
      wheezing and asthma. Therefore, eosinophil cationic protein (ECP) and interleukin
      8 (IL-8) levels in bronchoalveolar lavage fluid (BALF) from asthmatics (n = 16)
      and infantile wheezers (n = 30) were analyzed as markers of eosinophil- and
      neutrophil-mediated inflammation. To aid the interpretation, a control group of
      children (n = 10) with no lower airway pathology were included. Disease severity
      was assessed by using a symptom score. Surprisingly, no significant difference
      was found in IL-8 or ECP levels among asthma, infantile wheeze, and control
      groups. Asthma was characterized by: a correlation between ECP levels and
      eosinophil counts (r = 0.618, p = 0.014); a correlation between neutrophil number
      and IL-8 levels (r = 0.747, p = 0.002); and increasing IL-8 levels with symptom
      score (p = 0.03). In infantile wheezers, IL-8 levels were poorly related to
      neutrophil number but were significantly increased when neutrophils were > 10%.
      Although detectable levels were found in all but one symptomatic infant, IL-8
      concentrations did not reflect the symptom score in infantile wheeze. ECP was
      unexpectedly correlated to neutrophil percentages (Rho = 0.832, p = 0.001), and a
      threshold of ECP>20 ng/ml was associated with persistent symptoms in these
      infantile wheezers. Hence, in accordance with BALF cellularity, activation of
      eosinophils was suggested by raised levels of ECP in childhood asthma, but not in
      infantile wheeze. Neutrophil-mediated inflammation appeared to better reflect the
      severity of asthma than that of infantile wheeze. Although its meaning remains to
      be elucidated, ECP was suggested to be a helpful indicator of persistent
      infantile wheeze. However, its utility as a marker predicting ongoing asthma
      remains to be established.

PMID- 11251863
TI  - Urinary eosinophil protein X in children with asthma: influence of atopy and
      airway infections.
AB  - It has been suggested that urinary eosinophil protein X (U-EPX) can be used to
      monitor bronchial inflammation in childhood asthma. However, the influence of
      atopy and airway infections is not well elucidated. To determine the clinical
      value of measuring U-EPX in children with asthma and to evaluate the influence of
      atopy and airway infections, U-EPX was measured in 170 children with asthma (mean
      age 69 months, range 12-179 months), in 79 children with lower or upper
      respiratory tract infections (mean age 41 months, range 1-165 months), and in 64
      controls. U-EPX was elevated in children with acute asthma (median 132
      microg/mmol of creatinine, quartiles 77-195 microg/mmol of creatinine, n = 51, p
      <0.001) and chronic asthma (median 93 microg/mmol of creatinine; quartiles 46-149
      microg/mmol of creatinine, n = 119, p <0.01) compared with controls (median 54
      microg/mmol of creatinine, quartiles 40-89 microg/mmol of creatinine, n = 39).
      Atopic children had higher levels of U-EPX than non-atopics with acute asthma
      (median 155 microg/mmol of creatinine, quartiles 113-253 microg/mmol of
      creatinine, n = 27, vs. median 102 microg/mmol of creatinine, quartiles 56-168
      microg/mmol of creatinine, n = 24, p <0.05), as well as with chronic asthma
      (median 110 microg/mmol of creatinine, quartiles 65-162 microg/mmol of
      creatinine, n = 63, vs. median 60 microg/mmol of creatinine, quartiles 39-123
      microg/mmol of creatinine, n = 56, p <0.01). In chronic asthma, children without
      atopy had levels of U-EPX similar to values of controls; levels were similar in
      symptomatic and asymptomatic patients, and not influenced by treatment with
      inhaled corticosteroids. Moreover, U-EPX levels were higher in children with
      pneumonia (median 207 microg/mmol of creatinine, quartiles 111-280 microg/mmol of
      creatinine, n = 35, p <0.001), laryngitis (median 109 microg/mmol of creatinine,
      quartiles 65-161 microg/mmol of creatinine, n = 24, p <0.01), and rhinitis
      (median 172 microg/mmol of creatinine, quartiles 123-254 microg/mmol of
      creatinine, n = 19, p <0.001) than in controls (median 62 microg/mmol of
      creatinine, quartiles 41-93 microg/mmol of creatinine, n = 64). There was
      significant overlap among all groups of children with disease, as well as between
      children with disease and controls. Hence, U-EPX may reflect differences in
      eosinophil involvement and activation between children with atopic and non-atopic
      asthma, but the individual spread within groups and the influence of airway
      infections limits the clinical value of U-EPX in childhood asthma.

PMID- 11251864
TI  - Titres of specific antibodies to poliovirus type 3 and tetanus toxoid in saliva
      and serum of children with recurrent upper respiratory tract infections.
AB  - A study of antibody levels (in saliva and blood) against common vaccine antigens
      was performed in a population of 32 children suffering from recurrent upper
      respiratory tract infections (URTI). None of the patients had primary or
      secondary immunodeficiency syndromes or other known predisposing factors for
      respiratory diseases. Titres of the isotype-specific antibodies immunoglobulin A
      (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) against two vaccine
      antigens--poliovirus type 3 (P3) and tetanus toxoid (TT), a viral antigen and a
      bacterial antigen, respectively--were measured in unstimulated saliva and serum,
      both in patients and in 24 healthy children (controls), by using a standard
      enzyme-linked immunosorbent assay (ELISA). In addition, levels of total IgA and
      avidity of IgA antibodies to both P3 and TT in saliva were evaluated. No
      difference was found between patients and controls as to levels of total IgA, or
      specific IgA and IgM antibodies against both P3 and TT in saliva. Furthermore,
      the avidity of salivary IgA antibodies against the two antigens did not differ
      between the two populations. However, the average concentrations of saliva
      specific IgG antibodies to both the viral and the bacterial antigen were
      significantly lower (p <0.01 for P3 and p <0.05 for TT, respectively) in saliva
      of children with recurrent URTI, whereas no difference was found in serum for any
      immunoglobulin isotype determined compared with healthy individuals. The results
      of the present study provide suggestive evidence for the existence of subtle IgG
      restricted defects in antibody responses at the mucosal level, but not at the
      serum level, in some children with undue susceptibility to URTI.

PMID- 11251865
TI  - Recognition of asthmatic symptoms in the pediatric age group.
AB  - Asthma produces substantial morbidity in childhood. Under-diagnosis may lead to
      inappropriate treatment and prolonged periods of illness and absence from school.
      The results of a recent International Study of Asthma and Allergies in Childhood
      (ISAAC) questionnaire study in Malta showed a higher prevalence of wheezy
      symptoms in the Central North Region. The present study was carried out to test
      the null hypothesis that there is no correlation between potential exposure to
      pediatricians (measured as pediatric private clinics/1000 childhood
      population/week) and percentage of children aged 13-15 years of age responding
      positively in the questionnaire to having had wheezy symptoms. A significant,
      positive correlation was found between potential exposure to pediatricians and
      percentage of children aged 13-15 years responding positively to having had
      wheeze in the previous year (p=0.009). A negative correlation was also found for
      severity of asthma (>12 attacks in the previous 12 months) and potential exposure
      to pediatricians (p=0.01). This is the first report of potential exposure to
      pediatricians influencing the regional incidence of asthma on a national basis.
      This skew may be caused by the greater exposure of pediatricians to patients with
      severe forms of asthma in a hospital setting, and hence a higher index of
      suspicion for the milder forms of the disease. Asthma may be less severe in
      regions where there are a greater number of pediatricians because of recognition
      of the condition with appropriate treatment and/or prophylaxis.

PMID- 11251867
TI  - Health care access: a consumer perspective.
AB  - This article describes the use of action research as an information base for
      policy formulation by a collaborative partnership in Spokane, Washington. Health
      and social service providers recognized access to care by uninsured persons as a
      major community issue. Little was known from the consumers' perspective about
      factors limiting access. No benchmarks existed against which to measure progress.
      Investigators collected mailed surveys from 475 residents of six Spokane
      neighborhoods and 97 persons participated in 12 focus group sessions. Income,
      education, and ethnicity were primary factors affecting perceptions of degree to
      which medical, dental, and mental health needs were being met. Many residents
      were unable to obtain needed health care; low-cost dental and mental health
      services were named as their highest priorities. Quality of care, relationships
      with providers, immediacy of access, and cost were important concerns. Major
      barriers were cost, length of time before one could get an appointment, lack of
      comfort with providers, and having to miss work for appointments. Consumer input
      is critical in understanding local issues in health care. Action research that
      combines qualitative and quantitative data enhanced practice/policy decisions
      through assuring ownership of the research and immediate use of findings by
      involved agencies.

PMID- 11251869
TI  - The health of shelter-based foster youth.
AB  - There is a lack of information on the health needs of foster care adolescents in
      emergency shelters or group homes. The purpose of this study was to conduct an
      assessment of access to health care among shelter-based foster care adolescents
      in Baltimore, Maryland. The health passports of all the foster care youth staying
      at two emergency shelters had data extracted to a standardized chart audit tool.
      In addition, semistructured interviews were conducted with 15 of the adolescents
      and five shelter staff. Of the 84 passports, only nine (10.7%) had documented up
      to-date immunizations, and only one (1.2%) had documented purified protein
      derivative (PPD) application and reading. A total of 11 (13.1%) met the criteria
      for significant delay in recommended follow-up to care. Major themes of the
      interviews revealed that shelter staff and youth were unaware of specific health
      care recommendations, or were unable to obtain needed health care due to
      insurance problems or prolonged waiting for appointment times. The results of
      this health passport audit indicate that shelter-based foster care youth suffer
      from worse access to health care than do comparable nonshelter-based foster care
      youth from the same city. Specific public health nursing recommendations are made
      for improving health supervision for these vulnerable youth.

PMID- 11251868
TI  - Cost analysis: concepts and application.
AB  - Public health nurses are increasingly called upon to justify the cost of care or
      to decide which of two alternative programs is more cost-effective. Cost studies
      can be complex and difficult to conduct, but an understanding of the basic
      techniques allows nurses to fully participate in planning, implementing, and
      evaluating programs that greatly impact the health of the community. This article
      defines some of the basic terms used in health economics, discusses standard
      methods of cost analysis, and provides an example of neonatal screening to
      illustrate methods of describing, measuring, and assigning a value to cost items.

PMID- 11251870
TI  - Coping styles of pregnant adolescents.
AB  - This descriptive study examined the coping styles and specific strategies used by
      a group of pregnant adolescents attending an adolescent family support service.
      Seventy-one adolescents, with a mean age of 17 years, and a mean gestation of 25
      weeks, completed the Revised Jalowiec Coping Scale (JCS-R). The findings
      demonstrated that the optimistic coping style (emotion-focused) was the most
      frequently used and most effective coping style for these young women. A
      confrontive coping style (problem-focused) was also used and found to be
      effective. A combination of problem-focused and emotion-focused styles is
      recommended, with an increased emphasis on problem-focused approaches. The focus
      by the adolescents on optimistic approaches is suggestive of a lack of
      understanding of the challenges that motherhood will place upon them, but is
      consistent with their age and developmental stage. A longitudinal study of coping
      styles and changes in style throughout pregnancy and early motherhood is
      recommended. Initial assessment and monitoring of coping styles of pregnant
      adolescents is proposed. This assessment would be the beginning point for a
      teaching program that highlights increased use of adaptive coping styles (problem
      focused) with decreased use of maladaptive approaches, and includes emotion
      focused styles. By expanding the repertoire of coping styles and strategies
      available to the adolescent, the public health nurse (PHN) prepares these
      vulnerable mothers for the challenges ahead.

PMID- 11251871
TI  - Geographical mapping of unmarried teen births and selected sociodemographic
      variables.
AB  - Texas is one of five states in the United States in which teen pregnancies exceed
      70 per 1,000 females aged 15 to 17 years. The purpose of this retrospective
      exploratory study was to analyze and map sociodemographic variables associated
      with unmarried teen childbirth. It was hypothesized that selected
      sociodemographic variables would be related to the unmarried teen birthrates.
      Correlational analysis was employed to ascertain the relationship between the
      sociodemographic variables and the unmarried teen birthrates for 81 zip codes in
      Dallas County, Texas. The births occurred between January 1, 1995 and December
      31, 1996. Geographic Information System (GIS) software illustrated the spatial
      distribution of the unmarried teen birthrates in conjunction with
      sociodemographic variables extracted from the 1990 U.S. Census Bureau. The
      results indicate that unmarried teen births are positively related to low
      socioeconomic status, single-parent family households, and minority populations.
      Mapping supports the quantitative relationships between the variables. Maps can
      be used to identify communities where teens most vulnerable to unmarried
      pregnancy and childbirth reside and provide policy makers with explicit
      information about their constituents so that they can develop and implement
      population-specific interventions.

PMID- 11251872
TI  - Community assessment: a church community and the parish nurse.
AB  - In central Massachusetts a large urban parish asked the University of
      Massachusetts, Amherst School of Nursing to conduct a community assessment for
      the church and newly employed parish nurse. The aims of the assessment were: to
      determine the health status of parishioners, identify their perceived health
      needs and perceived barriers in meeting those needs, and to assist the church and
      parish nurse in developing a health program for their faith community. Findings
      of the assessment are based on questionnaire and focus group data. Four hundred
      and twenty-one questionnaires were completed, and six focus groups were held to
      validate the data. Results showed most parishioners felt they were in good health
      (93%), believed faith and spiritual beliefs were important in maintaining health
      and well-being (91%), and thought that the church should play a role in helping
      parishioners meet their health needs (70%). In addition, focus group discussions
      revealed a need for respite care for primary caretakers of the ill and elderly,
      and health education programs for their teen and elderly populations. In
      conclusion, parishioners were positive and articulated support of the parish
      nurse and activities designed to address the physical, emotional, and spiritual
      needs of their community.

PMID- 11251873
TI  - Pregnancy outcomes of inmates in a large county jail setting.
AB  - The purpose of this study was to examine low birthweight (LBW) and fetal death
      rates for women incarcerated in a large county jail during their pregnancy.
      Additionally, medical and support services available to these inmates were
      reviewed. Jail records showed this population to be both medically and socially
      high risk. Analysis indicated that their LBW rate was statistically higher (p <
      0.05) than that of the county or state, but comparable to a matched group
      residing in high-risk areas of the city in which many of these women resided.
      During the course of the study, numerous jail policies were identified which had
      the potential to negatively impact the health of these women and their pregnancy
      outcomes.

PMID- 11251874
TI  - Promoting positive affect and diminishing loneliness of widowed seniors through a
      support intervention.
AB  - Seniors are most vulnerable to conjugal bereavement. Although social support
      buffers the effects of bereavement, widows and widowers have lower levels of
      social support than married individuals. Self-help/support groups can supplement
      support from their depleted natural networks. Accordingly, the aim of this
      demonstration project was to examine the impact of support groups on widowed
      seniors' loneliness, affect, and perceived support. Four face-to-face support
      groups for widowed seniors were conducted weekly for a maximum of 20 weeks.
      Participants completed pretest, posttest, and delayed posttest measures of
      support need and support satisfaction, positive and negative affect, and
      loneliness/isolation. The statistically significant impacts of the intervention
      were enhanced support satisfaction, diminished support needs, and increased
      positive affect. There was a trend toward decreased social isolation and
      emotional loneliness. In postintervention semistructured interviews, bereaved
      seniors reported increased hope, improved skills in developing social
      relationships, enhanced coping, new role identities, and less loneliness.
      Community health nurse researchers could conduct randomized controlled trials of
      face-to-face and telephone support groups for bereaved people of all ages.
      Community health nurse practitioners could benefit from lessons learned about
      timing, duration, and selection of sensitive outcomes.

PMID- 11251875
TI  - Continence efficacy intervention program for community residing women with stress
      urinary incontinence in Japan.
AB  - Many women in Japan have lived with urinary incontinence (UI). These women are
      not willing to visit the hospital with their problem of incontinence. Even if the
      women consent to a hospital visit, continence education is often very limited and
      patients may immediately stop looking for further treatment. Programs of
      effective education are needed. The Continence Efficacy Intervention Program
      (CEIP) was developed for patients and was designed to circumvent many of the
      obstacles common to stopping exercise. In this study, a randomized trial was
      conducted to compare the effectiveness of this program to conventional
      intervention on exercise continuity. This report describes the study design,
      intervention program, and outcomes. Subjects were 48 women with stress urinary
      incontinence (SUI): the mean age was 53.5, the mean weight was 56.6 kg, and the
      average prevalent year was 6.5 years. The CEIP phone interviews improved exercise
      continuity and urine loss symptom. Findings suggest that this intervention
      program is effective and readily available to the community-residing women with
      SUI.

PMID- 11251876
TI  - Genetically manipulated bacterial toxin as a new generation mucosal adjuvant.
AB  - Cholera toxin (CT) and heat-labile toxin (LT) of Escherichia coli act as
      adjuvants for the enhancement of mucosal and serum antibody (Ab) responses to
      mucosally co-administered protein antigen (Ag). Both LT and CT induce B7-2
      expression on antigen-presenting cells (APCs) for subsequent co-stimulatory
      signalling to CD4+ T cells. CT directly affects CD4+ T cells activated via the
      TCR-CD3 complex with selective inhibition of Th1 responses whereas LT maintains
      Th1 cytokine responses with inhibition of interleukin (IL)-4 production.
      Interestingly, while CT failed to induce mucosal adjuvant activity in the absence
      of IL-4, LT did so. Nontoxic mutant (m)CTs (S61F and E112K) retain adjuvant
      properties by inducing CD4+ Th2 cells, which provided effective help for the Ag
      specific mucosal immunoglobulin (Ig)A, as well as serum IgG1, IgE and IgA Ab
      responses. The mCT E112K has been shown to exhibit two distinct mechanisms for
      its adjuvanticity. Firstly, mCT enhanced the B7-2 expression of APCs. Secondly,
      this nontoxic CT derivative directly affected CD4+ T cells and selectively
      inhibited Th1 cytokine responses. Thus, several lines of evidence indicate that
      enzyme activity can be separated from adjuvant properties of CT and this offers
      promise for the development of safe delivery of vaccines for mucosal IgA
      responses.

PMID- 11251877
TI  - Immunomodulation using bacterial enterotoxins.
AB  - Immunologic unresponsiveness (tolerance) is a key feature of the mucosal immune
      system, and deliberate vaccination by a mucosal route can effectively induce
      immune suppression. However, some bacterial-derived proteins, e.g. cholera toxin
      and the heat labile toxin of Escherichia coli, are immunogenic and
      immunomodulatory at mucosal surfaces and can effectively adjuvant immune
      responses to codelivered bystander antigens. This review summarizes some of the
      structural and biological characteristics of these toxins and provides examples
      of how these properties have been exploited for tolerance induction and mucosal
      vaccine development.

PMID- 11251878
TI  - New functions for the sialic acid-binding adhesion molecule CD22, a member of the
      growing family of Siglecs.

PMID- 11251879
TI  - Distinct amplification of the C5a-receptor pathways in normodense and hypodense
      eosinophils of patients with atopic dermatitis.
AB  - In patients with atopic dermatitis two different types of blood eosinophils with
      distinct density can be isolated. The normodense cells represent the huge
      majority in count, whereas the hypodense eosinophils are characterized by higher
      effector activity. To understand the altered functional responsiveness of these
      two cell subtypes, the expression of C5a receptors as well as C5a-induced signal
      pathways and the production of reactive oxygen metabolites have been analyzed.
      Chemiluminescence measurements revealed significant higher production of reactive
      oxygen metabolites in hypodense eosinophils in comparison to normodense cells.
      However, no difference in the expression level of C5a receptors as well as in the
      C5a-induced Ca2+-transients between normodense and hypodense eosinophils were
      found. In contrast, hypodense eosinophils showed a significantly higher actin
      polymerization response and phosphatidylinositol 4,5 bisphosphate 3-kinase
      activation after stimulation with C5a than normodense eosinophils. Therefore,
      normodense and hypodense eosinophils from the blood of patients with atopic
      dermatitis are characterized by differential amplification of C5a-receptor signal
      pathways, which might explain the differences in their proinflammatory activity.

PMID- 11251880
TI  - T-cell enforced invariance of the antibody repertoire in the immune response
      against a bacterial carbohydrate antigen.
AB  - The humoral response against the bacterial polysaccharide antigen alpha(1-->3)
      dextran (Dex) is controlled by J558 idiotype-(Id) specific T cells. These T cells
      of which the cell clone 178-4 Ts is a representative by all relevant criteria,
      recognize J558 Id-bearing B cells in an I-Ed-restricted manner. Costimulation via
      CD28/B7-1 but not via CD40/CD40L leads to T-cell activation. These T cells do not
      only suppress B cells producing the immunoglobulin (Ig)G3 isotype but also
      support the survival and clonal expansion of J558 Id positive B cells both in
      vivo and in vitro. This T-cell mediated dominance of the J558 idiotype limits the
      appearance of antibodies carrying other more diverse idiotypes which appear in
      immunized BALB/c nu/nu mice where no regulatory T cells occur. This T-cell
      mediated antibody invariance could be a strategy of the immune system responding
      to highly conserved antigens like polysaccharides, different from those against
      protein antigens, where diversity is assumed to be the basis for a successful
      response.

PMID- 11251886
TI  - An investigation into the heparin-binding properties of a synthetic peptide
      deduced from the antigenic domain 2 of human cytomegalovirus glycoprotein B.
AB  - An investigation was performed into the heparin-binding properties of a synthetic
      peptide deduced from the sequence of human cytomegalovirus glycoprotein B. The
      peptide, T7-13:3, amino acids 69-78, which was previously shown to contain a
      neutralization epitope was able to bind heparin coated onto microtitre plates as
      well as immobilized on agarose beads. Conversely, labelled heparin could be used
      to specifically detect the immobilized peptide. The peptide bound to human cells
      in a manner which suggested an interaction with extracellular matrix, and binding
      of the peptide to human fibroblasts could be inhibited both by adding soluble
      heparin and by enzymatic pretreatment of the cells with heparinase. The sequence
      of T7-13:3 shows similarity to several proteins with known or supposed ability to
      bind heparin, e.g. basic fibroblast growth factor, the heparin-binding capacity
      of which could also be inhibited by T7-13:3. The peptide was also found to bind
      DNA, probably due to the similarities between DNA and heparin in terms of
      structure and charge. Because heparin is a chemical homologue of heparan sulfate,
      the results strongly indicate that the sequence represented by T7-13:3 is
      involved in the binding of virus to cell surface heparan sulfate. The described
      region of gB may have the potential to contribute to a subunit vaccine although
      possible hazards, such as the induction of auto-antibodies to heparin, and thus
      also to DNA, need to be considered.

PMID- 11251888
TI  - Activation of T cells in the blood of patients with acute malaria: proliferative
      activity as indicated by Ki-67 expression.
AB  - The expression of the proliferation-associated nuclear antigen Ki-67 in
      peripheral blood mononuclear cells was studied in 30 patients with acute malarial
      illness and 11 healthy controls from Addis Ababa or Nazareth in Ethiopia.
      Seventeen patients had Plasmodium falciparum infections and 13 had Plasmodium
      vivax. Two-colour immunoenzymatic staining was developed in order to
      simultaneously detect the expression of the nuclear antigen Ki-67 and determine
      the surface phenotype of the cell. The median percentage of proliferating, Ki-67
      positive lymphocytes was significantly higher in patients with acute P.
      falciparum (11.8%) and P. vivax (15.6%) illnesses compared to the controls
      (4.3%). The majority of Ki-67 positive cells were T cells (CD3+) while the
      relative increase of Ki-67 expressing cells was similar for both the CD4+ and
      CD8+ T-cell subsets. Our data show an increased number of activated cells driven
      to proliferation in the peripheral blood of patients during acute malaria
      illness.

PMID- 11251882
TI  - Anti-idiotype antibodies neutralize in vivo the blistering effect of Pemphigus
      foliaceus IgG.
AB  - Idiotypes are molecular clues used to explore the specificity and diversity of
      immune response. In the present study, anti-idiotype antibodies were used to
      neutralize the pathogenic effects induced by the injection of pemphigus
      immunoglobulin(Ig)G into BALB/c mice. To achieve our goal, antidesmoglein 1 IgG
      was obtained from a patient with pemphigus foliaceus with high titer of
      antiepithelial antibodies. The IgG was isolated by ion exchange chromatography,
      then digested by pepsin. F(ab')2 fragments were purified in Sephacryl S-300 and
      injected in rabbits to produce anti-idiotype antibodies. The rabbit sera reacted
      with the pemphigus F(ab')2 fragments. Eleven pemphigus foliaceus sera were
      recognized by the anti-idiotype serum at the light or heavy chains whereas
      bullous pemphigoid and normal IgG were negative. Neonatal BALB/c mice injected
      with pemphigus IgG developed intraepidermal blisters, mimicking the clinical and
      immunopathological features of the pemphigus. In contrast, the animals treated
      with anti-idiotype antibodies and pemphigus IgG did not develop blisters. Thus,
      anti-idiotype antibodies neutralize in vivo the pathogenic effects of pemphigus
      IgG.

PMID- 11251881
TI  - Role of CD8+ cell-produced anti-viral factors in protective immunity in HIV-2
      exposed but seronegative macaques resistant to intrarectal SIVsm challenge.
AB  - The cell-mediated immune response is likely to be important in controlling
      HIV/SIV infection. There is evidence that beta-chemokines and other, as yet
      unknown, anti-viral factors play a role in host defence against HIV infection. We
      reported previously that HIV-2 exposed but seronegative cynomolgus macaques
      developed SIV-specific cytotoxic T lymphocytes and were resistant to mucosal SIV
      challenge. The aim of this study was to examine CD8+ cell-dependent production of
      beta-chemokines and other anti-viral factors in these macaques. The animals,
      selected from among 17 monkeys enrolled in two separate experiments, were either
      treated with an anti-viral drug or immunized passively with HIV-2 antibody
      positive serum. Three of these monkeys were protected against repeated HIV-2
      challenge and were also able to control SIV infection 3 years later. Control
      samples were obtained from four macaques that became SIV infected and from 39
      naive animals. The three resistant monkeys showed significantly higher production
      of RANTES and MIP-1alpha than the 39 naive animals. In addition, SIV infection
      was suppressed by CD8+ cell culture supernatants of these monkeys. However,
      antibodies to chemokines only partially neutralized CD8+ cell-mediated SIV
      suppression indicating that the anti-viral activity observed in these monkeys was
      the result of combined action of several inhibitory factors.

PMID- 11251887
TI  - Intranasal administration of one alpha gliadin can downregulate the immune
      response to whole gliadin in mice.
AB  - The mucosal lesion present in coeliac disease is an immune-mediated injury
      triggered by gliadin and restricted by a particular assortment of major
      histocompatibility complex genes. In view of this, an immunomodulatory approach
      that induces tolerance to this antigen appears to be a possible alternative to a
      strict gluten-free diet in treating coeliac disease. We have shown that
      intranasal administration of multiple doses of whole gliadin is required to
      specifically inhibit T helper 1-like T-cell reactivity in BALB/c mice immunized
      parenterally with whole gliadin. However, T-cell activation to multiple antigens,
      as a consequence of the chemical complexity shown by the antigen gliadin, could
      hamper efforts to identify single component(s) useful for tolerance induction. In
      this study, gliadin fractions were purified and administered intranasally to
      study their ability to induce tolerance to whole gliadin in our animal model. We
      found that the alpha fraction was particularly effective in downregulating both
      the in vitro gliadin-specific T-cell proliferation and interferon-gamma
      production to whole gliadin. In particular, a purified alpha-gliadin was able to
      suppress the immune response to the entire gliadin mixture. These results
      demonstrate how an immune response to a complex antigen may be controlled by
      treatment with a purified component and specifically indicate alpha-gliadin to be
      a good candidate for further identification of short peptides to be used as
      tolerogens in this model.

PMID- 11251883
TI  - Modulation of CD8 and CD3 by HIV or HIV antigens.
AB  - To investigate whether human immunodeficiency virus (HIV)-1 and HIV-1 antigens
      modulate surface and cytoplasmic CD8 or CD3, as well as CD4, we used cell
      permeabilization reagents, surface/cytoplasmic fluorescent staining,
      multiparameter flow cytometric techniques and an in vitro culture system in which
      relatively few lymphocytes are actively infected with HIV. Human peripheral blood
      lymphocytes were: not stimulated, not stimulated but HIV-inoculated,
      phytohaemagglutinin (PHA)-stimulated, PHA/HIV-inoculated (PHA/HIV), or placed
      into media with soluble gp120, Rev or Nef. HIV inoculation and Nef had striking
      modulatory effects on CD8. The cytoplasmic CD8 median fluorescent intensity (MFI)
      of positive lymphocytes was lower for cells in unstimulated/HIV-infected cultures
      than unstimulated cultures (44 versus 62% of ex vivo value, P = 0.032) and lower
      for cells in PHA/HIV cultures than in PHA cultures (56 versus 100% of ex vivo, P
      = 0.041). The surface CD8 MFI values for Nef were significantly lower than the ex
      vivo value (75% of ex vivo, P = 0.006). At days 2-7 of culture, Rev was
      associated with slight reductions in surface CD4 MFI (58% of ex vivo versus 78%
      of ex vivo for unstimulated cultures, P = 0.047) and greater effects on
      cytoplasmic CD3 MFI (131 versus 179% of ex vivo for unstimulated cultures, P =
      0.035), and surface CD8 MFI (70% of ex vivo, P = 0.006 versus ex vivo value). The
      globality of Rev's effects suggests these are related to a shared processing
      pathway, i.e. not due to direct interaction with CD3, CD4 and CD8; the effects of
      HIV inoculation and Nef on CD8 expression appear to be more CD8 specific. Because
      CD8 is essential for cytotoxic T-cell function, its down-modulation could inhibit
      this activity, including anti-HIV cytotoxicity. Given the critical roles of CD3
      and CD8 in T-lymphocyte signal transduction and antigen responsiveness, the
      effects of HIV, Rev and Nef on these molecules have clinically significant
      implications concerning the pathogenesis and treatment of HIV.

PMID- 11251892
TI  - Global-national-local.

PMID- 11251885
TI  - Administration of BiMAb-retargeted T cells in a rat hepatic metastases colon
      tumour model results in T-cell tumour infiltration independent of the route of
      administration.
AB  - In this study, cultured T cells, pre-incubated with the bispecific monoclonal
      antibody (BiMAb) R73IgG1 x CC52IgG1 were adoptively transferred, via systemic and
      regional routes, to rats bearing day 10 hepatic metastases of the CC531
      adenocarcinoma of the colon to investigate the role of the route of
      administration in tumour infiltration by these BiMAb-retargeted effector cells.
      The BiMAb, directed against the T-cell receptor and the tumour-associated antigen
      CC52, were used to crosslink CC531 tumour cells and T cells to induce tumour cell
      lysis. Retargeted T cells were administered via the jugular vein, hepatic artery
      or the portal vein. The number of BiMAb-retargeted T cells that reached the liver
      tumours was independent of the route of administration. There was also no
      difference between the number of T cells that reached the portal tracts, central
      veins of parenchyma of the liver, after loco-regional or systemic administration.
      These findings are in contrast to the interleukin (IL)-2 activated NK (A-NK)
      cells biodistribution studies earlier performed in the same animal model in our
      laboratory. Compared with A-NK cells, a lower number of BiMAb-retargeted T cells
      reached the tumours, irrespective of their route of administration while for A-NK
      cells, there was an advantage of administration via the hepatic artery.

PMID- 11251889
TI  - Vertical HIV-1 transmission: importance of neutralizing antibody titer and
      specificity.
AB  - Neutralization analyses were carried out with plasma from 132 volunteer human
      immunodeficiency virus (HIV)-1 infected women (76% pregnant, 24% with infants
      suspected for HIV-1 infection) collected between 1994 and 1998, against
      autologous and heterologous primary- and the reference HIV-1 MN isolates. A
      significantly lower percentage of HIV-1 transmissions was observed after 1996,
      parallel to a more intense antiretroviral treatment of infected pregnant women.
      HIV-1 isolation was significantly more frequent from peripheral blood mononuclear
      cells of mothers of infected children than mothers of uninfected children (P =
      0.0065). Neutralization of autologous HIV-1 isolates was comparable for HIV-1
      transmitters and nontransmitters' plasma, whereas neutralization of the reference
      isolate HIV-1 MN was more frequent at high titers for pregnant women who did not
      transmit HIV to their offspring compared to pregnant women who did. Although
      neutralization of heterologous primary HIV-1 isolates from HIV transmitters and
      non transmitters by transmitter plasma occurred with similar frequency,
      neutralization of isolates from transmitters was much more frequent when
      heterologous plasma from nontransmitters were used. Macrophage-tropic
      heterologous HIV-1 isolates were neutralized more frequently at higher titers by
      plasma from nontransmitters than from transmitters. The results obtained indicate
      that antiretroviral treatment, lack of success of HIV-1 isolation and high titers
      of antibodies able to neutralize macrophage-tropic viruses appear to be of
      importance for protection against HIV-1 vertical transmission for the group of
      patients studied.

PMID- 11251890
TI  - Cytokine levels in midtrimester amniotic fluid in normal pregnancy and in the
      prediction of pre-eclampsia.
AB  - Midtrimester amniotic fluid cytokines may reflect the function of the maternal
      immune system in the maternal-fetal interface and thus be predictive of pre
      eclampsia. We determined the concentrations of interleukin (IL)-6, IL-8, IL-10,
      IL-11, IL-12, IL-15, tumour necrosis factor (TNF)-alpha and transforming growth
      factor (TGF)-beta in amniotic fluid at 14-16 weeks of gestation from women with
      normal pregnancies and from those who subsequently developed severe pre
      eclampsia. The concentrations of the cytokines in amniotic fluid did not
      significantly differ between patients and normal controls. The median
      concentration of IL-6 was 950 pg/ml in normal pregnant women and 578 pg/ml in the
      patient group. The median concentration of IL-8 was 606 pg/ml in normal controls
      and 294 pg/ml in the patient group. The levels of IL-6, IL-8 and TGF-beta
      correlated positively with each other. TNF-alpha concentrations were low and
      similar in both groups. IL-10 and IL-12 were detected at very low levels in 37
      and 7% of the samples, respectively. No difference was found in IL-15
      concentrations between the groups. IL-11 was found only at low levels in both
      groups. Although none of the cytokines measured was predictive of pre-eclampsia,
      this study provides information of cytokines in amniotic fluid during the period
      when the spiral arteries are remodelled.

PMID- 11251891
TI  - Effects of subcutaneous IL-2 therapy on telomere lengths in PBMC in HIV-infected
      patients.
AB  - In this study we investigated the effect of interleukin-2 (IL-2) on mean terminal
      restriction fragment (TRF) lengths in peripheral blood mononuclear cells (PBMC).
      Ten human immunodeficiency virus (HIV)-infected individuals were included and IL
      2 was administered subcutaneously with 3 x 106 IU three times a week for 24
      weeks. Mean TRF length was decreased on average by 267 bp at week 4 (P = 0.03)
      and 286 bp at week 8 (P = 0.09). Individual TRF changes at weeks 12, 16, 20 and
      24 were highly variable. However, in the 12 weeks following therapy, TRF lengths
      generally increased reaching baseline levels by the end of the study. At
      baseline, mean TRF lengths were positively correlated to the ratio of naive and
      memory phenotype within both CD4+ and CD8+ cells. This study shows that IL-2
      treatment induces transient shortened mean TRF lengths in PBMC from HIV-infected
      individuals, indicating that IL-2 enhances the lymphocyte count by peripheral
      proliferation or recruitment of memory T cells into the blood.

PMID- 11251893
TI  - Global, national, and local approaches to mental health: examples from India.
AB  - Neuropsychiatric disorders and suicide amount to 12.7% of the global burden of
      disease and related conditions (GBD) according to World Health Organization (WHO)
      estimates for 1999, and recognition of the enormous component of mental illness
      in the GBD has attracted unprecedented attention in the field of international
      health. Focusing on low- and middle-income countries with high adult mortality,
      this article discusses essential functions of international agencies concerned
      with mental health. A review of the history and development of national mental
      health policy in India follows, and local case studies consider the approach to
      planning in a rural mental health programme in West Bengal and the experience in
      an established urban mental health programme in a low-income community of Mumbai.
      Local programmes must be attentive to the needs of the communities they serve,
      and they require the support of global and national policy for resources and the
      conceptual tools to formulate strategies to meet those needs. National programmes
      retain major responsibilities for the health of their country's population: they
      are the portals through which global and local interests, ideas, and policies
      formally interact. International priorities should be responsive to a wide range
      of national interests, which in turn should be sensitive to diverse local
      experiences. Mental health actions thereby benefit from the synergy of informed
      and effective policy at each level.

PMID- 11251884
TI  - Autoantibody to the leucine zipper region of 52 kDa Ro/SSA binds native 60 kDa
      Ro/SSA: identification of a tertiary epitope with components from 60 kDa Ro/SSA
      and 52 kDa Ro/SSA.
AB  - Anti-Ro (or SSA) is found in the sera of patients with autoimmune rheumatic
      illnesses. All patients with anti-Ro defined by precipitation bind a 60 000 Da
      antigen (60 kDa Ro), whereas some patients also bind a 52 000 Da molecule (52 kDa
      Ro). In general, antibody binding is directed against native 60 kDa Ro and
      denatured 52 kDa Ro. The mechanism by which anti-52 kDa Ro arises in the setting
      of anti-60 kDa Ro is unknown. Conflicting data exist as to the existence of a
      physical interaction between the two proteins in cells and as to cross-reacting
      antibodies. Antibodies were affinity purified from a peptide within the leucine
      zipper region of 52 kDa Ro. These purified antibodies binding the 197-207 peptide
      from 52 kDa Ro (anti-52LZ) bound native 60 kDa Ro as well as denatured 52 kDa Ro.
      In addition, anti-52LZ also bound up to four regions from the sequence of 60 kDa
      Ro and a single conformational epitope of 60 kDa Ro. Thus, these primary sites
      represent components of the tertiary epitope. We hypothesized that if this was
      the case, these peptides making up a tertiary epitope would show molecular
      interaction. In fact, peptides from 60 kDa Ro have a molecular interaction with
      the 52 kDa Ro peptide as well as full-length 52 kDa Ro when assessed by surface
      plasmon resonance. The leucine-zipper region peptide from 52 kDa Ro bound three
      of the four peptides from 60 kDa Ro. These data suggest that these two molecular
      species, 60 and 52 kDa Ro, form a conformational epitope. This relationship may
      explain why anti-52 kDa Ro is found in association with anti-60 kDa Ro.

PMID- 11251894
TI  - Effect of aggressive prolonged diethylcarbamazine therapy on circulating antigen
      levels in bancroftian filariasis.
AB  - BACKGROUND: Single dose diethylcarbamazine (DEC) as used in control programmes is
      effectively microfilaricidal for periods of up to a year or more but has
      incomplete ability to kill Wuchereria bancrofti adult parasites. These regimens
      can be effective in breaking transmission by suppression of circulating
      microfilariae available to mosquito vectors. Whether prolonged or aggressive
      therapy with DEC has a significant effect on adult worms, which may live up to 12
      years or more, and is important in the context of the treatment of individual
      patients, is still incompletely understood. METHODS: In order to investigate the
      adulticidal effect of aggressive therapy, DEC was given at 6 mg/kg/day for 12-day
      courses at 0, 6, 12, and 18 months and Og4C3 antigenaemia followed over two years
      in 38 CAg + Brazilians in a W. bancrofti endemic area. RESULTS: At two year
      follow-up, the median level of antigenaemia was 21% of the pre-treatment value.
      92% of individuals had antigen levels < 50% of pretreatment values, but only 26%
      had completely cleared antigenaemia. The clearance rate at 24 months was only 12%
      (3/26) in the asymptomatic CAg + patients but 58% (7/12) in those with clinical
      manifestations of filariasis. The latter individuals cleared significantly more
      antigen (median of 0% pretreatment antigenaemia vs. 26%; P=0.02) than
      asymptomatic but infected individuals. CONCLUSION: Aggressive repeated therapy
      with DEC alone is ineffective in consistently eradicating adult W. bancrofti,
      especially in infected but asymptomatic individuals. Prolonged courses of
      combination therapy with other antifilarial drugs should be investigated for
      treatment of individual patients with the means to pursue aggressive personal
      medical care.

PMID- 11251898
TI  - Aedes aegypti in French Guiana: susceptibility to a dengue virus.
AB  - Twenty-seven samples of Aedes aegypti (F1 generation) from French Guiana were
      tested for their susceptibility to dengue serotype 2 virus. Very high infection
      rates were observed by indirect fluorescent antibody (IFA) test. Ae. aegypti
      samples were pooled according to two groups: the first group (N=10) represented
      mosquitoes from the urbanized area of Cayenne and surroundings, and the second
      group (N=17) corresponded to mosquitoes collected in the countryside. Infection
      rates were found to be similar in these two cases. These findings are discussed
      in relation with the history of Ae. aegypti in this part of the world.

PMID- 11251896
TI  - Shigella and Salmonella strains isolated from children under 5 years in Gaborone,
      Botswana, and their antibiotic susceptibility patterns.
AB  - We isolated Shigella from 43/221 (21%) and Salmonella 8/221 (3%) rectal swabs
      from children under 5 years with diarrhoea, and found Shigella in two of 100
      specimens from children without diarrhoea. Sh. boydii (13%) was the most
      prevalent Shigella species followed by Sh. flexneri (6%) and Sh. sonnei (2%). The
      prevalence of various types of Sh. boydii was type 7, 5%; type 9, 3%; type 12 and
      16, 2%; and type 18, 1%. Other Shigella serotypes encountered were Sh. flexneri
      type 6 (4%), type 4 (2%), with Sh. sonnei phase II isolated from 2% of the
      specimens. The Salmonella species were S. typhimurium and S. paratyphi. The high
      rate of isolation of Shigella species from children with diarrhoea is indicative
      of a definite role of this enteropathogen in causing endemic diarrhoea in
      Gaborone, Botswana. Antibiograms of the predominant isolates showed that most
      Shigella species were resistant to ampicillin but susceptible to chloramphenicol,
      and with the exception of Sh. flexneri type 6, also susceptible to gentamicin.
      The Salmonella species were susceptible to chloramphenicol, collistin-sulphate,
      gentamicin, cotrimoxazole, and ampicillin.

PMID- 11251895
TI  - Irrigation water as a source of drinking water: is safe use possible?
AB  - BACKGROUND: In arid and semi-arid countries there are often large areas where
      groundwater is brackish and where people have to obtain water from irrigation
      canals for all uses, including domestic ones. An alternative to drawing drinking
      water directly from irrigation canals or village water reservoirs is to use the
      water that has seeped from the irrigation canals and irrigated fields and that
      has formed a small layer of fresh water on top of the brackish groundwater. The
      objective of this study was to assess whether use of irrigation seepage water for
      drinking results in less diarrhoea than direct use of irrigation water and how
      irrigation water management would impact on health. METHODS: The study was
      undertaken in an irrigated area in the southern Punjab, Pakistan. Over a one-year
      period, drinking water sources used and diarrhoea episodes were recorded each day
      for all individuals of 200 households in 10 villages. Separate surveys were
      undertaken to collect information on hygiene behaviour, sanitary facilities, and
      socio-economic status. RESULTS: Seepage water was of much better quality than
      surface water, but this did not translate into less diarrhoea. This could only be
      partially explained by the generally poor quality of water in the in-house
      storage vessels, reflecting considerable in-house contamination of drinking
      water. Risk factors for diarrhoea were absence of a water connection and water
      storage facility, lack of a toilet, low standard of hygiene, and low socio
      economic status. The association between water quality and diarrhoea varied by
      the level of water availability and the presence or absence of a toilet. Among
      people having a high quantity of water available and a toilet, the incidence rate
      of diarrhoea was higher when surface water was used for drinking than when
      seepage water was used (relative risk 1.68; 95% CI 1.31-2.15). For people with
      less water available the direction of the association between water quality and
      diarrhoea was different (relative risk 0.80; 95% CI 0.69-0.93). This indicates
      that good quality drinking water provides additional health benefits only when
      sufficient quantities of water and a toilet are available. In a multivariate
      analysis no association was found between water quality and diarrhoea but there
      was a significant effect of water quantity on diarrhoea which was to a large
      extent mediated through sanitation and hygiene behaviour. CONCLUSIONS: Increasing
      the availability of water in the house by having a household connection and a
      storage facility is the most important factor associated with reduced diarrhoea
      in this area. Safe use of canal irrigation water seems possible if households can
      pump seepage water to a large storage tank in their house and have a continuous
      water supply for sanitation and hygiene. Irrigation water management clearly has
      an impact on health and bridging the gap between the irrigation and drinking
      water supply sectors could provide important health benefits by taking into
      account the domestic water availability when managing irrigation water.

PMID- 11251899
TI  - Short communication: Lassa fever in Sierra Leone: UN peacekeepers are at risk.

PMID- 11251897
TI  - Costs of tuberculosis for households and health care providers in Dar es Salaam,
      Tanzania.
AB  - OBJECTIVE: To assess the costs of tuberculosis at household level in Dar es
      Salaam and to compare them with the provider costs of the national tuberculosis
      control programme. DESIGN: Tuberculosis patients were found by active case
      searching within a routine census in three areas of Dar es Salaam, and by
      examining records for residents already receiving treatment. Costs at household
      level were evaluated through a cross-sectional household survey. RESULTS: One
      hundred and ninety-one tuberculosis cases were included in the survey. With
      treatment periods of 8 to 12 months, extrapolated average costs of a period of
      illness to patients and their families were as follows: US 2 dollars for
      examination and laboratory costs, between US 17 dollars and US 50 dollars for
      consultation and drugs, less than US 1 dollar for hospitalization and between US
      13 dollars and US 20 dollars for transport. The analysis revealed high costs due
      to inability to work, ranging from US 154 dollars to US 1384 dollars. These data
      were compared with the operation costs of the tuberculosis programme and proved
      to comprise 68% to 94% of total costs. CONCLUSIONS: For patients and their
      families, tuberculosis implies three main types of cost: drugs, transportation
      and, most importantly, financial loss due to inability to work. They represent
      around two thirds of total cost and are a high economic burden for households, in
      particular those with a low-income. While assessing tuberculosis control
      strategies such as direct case finding at home, it is therefore important to also
      include costs incurred at household level.

PMID- 11251900
TI  - Are people in rural African communities willing to pay for the re-treatment of
      insecticide-impregnated nets (ITNs)?

PMID- 11251902
TI  - Female genital cutting: distinguishing the rights from the health agenda.

PMID- 11251904
TI  - Paracheck-Pf: a new, inexpensive and reliable rapid test for P. falciparum
      malaria.
AB  - We compared the performance of Paracheck-Pf, a new and cheap rapid malaria test,
      with ICT-Pf/PvR and microscopy in two malaria surveys in Thai villages on the
      Thai-Burmese border. The specificity, sensitivity, predictive positive and
      negative values of the Paracheck-PfR and ICT-PfR tests were calculated taking
      microscopy results as the gold standard. The 294 ICT-Pf/Pv tests resulted in two
      invalid (no control line) and 11 doubtful results. Both the ICT-Pf/PvR and
      Paracheck-PfR tests reliably detected P. falciparum infections. However,
      Paracheck-PfR failed to detect three P. falciparum cases and likewise, ICT-Pf/PvR
      failed to detect the same three cases and an additional four cases. These seven
      cases were detected by microscopy and had a parasitaemia under 150
      parasites/microl. At a cost of c. US $1.00, the Paracheck-PfR test, based on the
      detection of the P. falciparum specific HRP-2 protein, is a reliable, easy to use
      and affordable tool for the diagnosis of P. falciparum malaria.

PMID- 11251903
TI  - Parasitaemia and gametocytaemia after treatment with chloroquine,
      pyrimethamine/sulfadoxine, and pyrimethamine/sulfadoxine combined with artesunate
      in young Gambians with uncomplicated malaria.
AB  - As part of a study to assess the infectivity of gametocytes after treatment with
      four antimalarial regimens, the efficacy of each treatment was also determined.
      From September to December 1998, 598 children with uncomplicated malaria were
      treated; 135 received chloroquine (CQ) alone, 276 received
      pyrimethamine/sulfadoxine (Fansidar, PSD) alone, 113 received PSD with a single
      dose of artesunate (PSD + 1ART) and 74 received PSD combined with three doses of
      artesunate (PSD + 3ART). On day 28 19/63 (30.2%; 95% C.I. 19.2% to 43.1%) of
      children treated with CQ alone, 5/134 (3.7%; 95% C.I. 1.2% to 8.5%) treated with
      PSD alone, 1/71 (1.4%, 95% C.I. 0.0% to 7.9%) treated with PSD + 1ART and 0/45
      (0.0%; 95% C.I. 0.0% to 7.9%) treated with PSD + 3ART were parasitaemic. The
      proportion of children with gametocytes on day 7 after treatment with CQ alone
      was 16/89 (18.0%; 95% C.I. 10.6% to 27.6%), 98/174 (56.3%; 95% C.I. 48.6% to
      63.8%) after treatment with PSD alone, 8/70 (11.4%; 95% C.I. 5.1% to 21.3%) after
      treatment with PSD + 1ART and 4/46 (8.7%; 95% C.I., 2.4% to 20.8%) after
      treatment with PSD + 3ART. CQ thus has a lower efficacy than PSD or either of the
      PSD and artesunate combinations. Use of PSD alone as an alternative first line
      treatment results in a very high post-treatment gametocyte prevalence that is
      likely to enhance transmission. There would be greater and more sustainable
      benefits from using PSD and artesunate combinations.

PMID- 11251908
TI  - Antibodies to tetanus toxoid in women of childbearing age in Dar es Salaam and
      Bagamoyo, Tanzania.
AB  - Our aim was to determine tetanus immunity in women of childbearing age (15-44
      years) with histories and/or documentation of having been vaccinated with Tetanus
      Toxoid (TT) under the Expanded Programme on Immunization in Dar es Salaam and
      Bagamoyo, Tanzania. Using an ELISA technique, serum levels of TT antibody,
      antibody avidity and distribution of TT IgG subclass antibodies were determined
      in 207 apparently healthy women. A TT antibody level of 0.1 IU/ml was considered
      protective. 99% and 100% of women in Dar es Salaam and Bagamoyo, respectively,
      had a TT antibody level > or = 0.1 IU/ml. Anti-toxin binding avidity was found to
      be high in most of the women. In addition to TT IgG3 subclass antibody, TT IgG1
      subclass antibody was the most dominant subclass type. A substantial number of
      women also had TT IgG2 and TT IgG4 subclass antibody responses. A better
      recording system on TT immunization is recommended to avoid hyper-immunization of
      women and to optimize the cost-effectiveness of the immunization programme.

PMID- 11251905
TI  - Evidence for a reduced effect of chloroquine against Plasmodium falciparum in
      alpha-thalassaemic children.
AB  - Alpha-thalassaemia is common in malaria-endemic regions and is considered to
      confer protection from clinical disease due to infection with Plasmodium
      falciparum. In vitro, sensitivity to chloroquine (CQ) of P. falciparum infecting
      alpha-thalassaemic erythrocytes is reduced. We examined, in a cross-sectional
      study of 405 Nigerian children, associations between alpha-globin genotypes,
      blood concentrations of CQ, and P. falciparum parasitaemia. Of the children, 44%
      were alpha+-thalassaemic (36.8% heterozygous, 7.6% homozygous). CQ in blood and
      P. falciparum-infection were observed in 52 and 80%, respectively. CQ was more
      frequently found in homozygous alpha+-thalassaemic (71%) than in non-thalassaemic
      children (50%; odds ratio, 2.42; 95% confidence interval, 1.01-5.8). Among
      children with CQ in blood and despite similar drug concentrations, alpha+
      thalassaemic individuals had fewer infections below the threshold of microscopy
      which were detectable by PCR only, and they had a higher prevalence of elevated
      parasitaemia than non-thalassaemic children. No such differences were discernible
      among drug-free children. CQ displays a lowered efficacy in the suppression of P.
      falciparum parasitaemia in alpha+-thalassaemic children; hence protection against
      malaria due to alpha+-thalassaemia may be obscured in areas of intense CQ usage.
      Moreover, alpha+-thalassaemia may contribute to the expansion of CQ resistance.

PMID- 11251911
TI  - Consequences of over-prescribing on the dispensing process in rural Nepal.
AB  - OBJECTIVE: To investigate the effect of increasing numbers of drugs prescribed on
      the dispensing process in rural Nepal. DESIGN: Cross-sectional survey, on average
      25 exiting patients per facility in 33 government health facilities. OUTCOME
      MEASURES: Percentage of cases where there was a dispensing error, and where the
      patient knew the dosing schedules of the dispensed drugs. RESULTS: A greater
      number of drug items prescribed and dispensed per patient was significantly
      associated with a greater percentage of cases where there was a dispensing error
      (P=0.00000), and where the patient did not know the dosing schedules of the
      dispensed drugs (P=0.00000). CONCLUSION: The prescribing (and dispensing) of more
      drugs per patient, an indication of over-prescription, is associated with
      significantly poorer dispensing.

PMID- 11251907
TI  - Latex based, rapid and easy assay for human leptospirosis in a single test
      format.
AB  - Leptospirosis is an often severe disease which requires prompt treatment.
      Laboratory testing is required to reach a valid diagnosis. An agglutination assay
      for the detection of Leptospira-specific antibodies consisting of individually
      wrapped agglutination cards containing a stable, dried detection reagent is
      evaluated. The assay is simply performed by suspending the dried reagent with a
      drop of serum. The result is obtained within 30 s. The sensitivity of the assay
      varied with the stage of the disease and was 72.3% for samples collected during
      the first 10 days of the illness and 88.2% for samples collected at a later
      stage. The specificity was 93.9% and 89.8%, respectively. These characteristics
      make the test ideal for use in areas where the disease is common and where
      laboratory support is not routinely available.

PMID- 11251909
TI  - Exposure to Schistosoma mansoni infection in a rural area of Brazil. I: water
      contact.
AB  - The study of water contact patterns in rural Brazil presents unique challenges
      due to widely dispersed settlement patterns, the ubiquity of water contact sites,
      and the privatization of water resources. This study addresses these challenges
      by comparing the two most widely used methods of assessing water contact
      behaviour: direct observation and survey. The results of a 7-day direct
      observation of water contact were compared with water contact surveys
      administered 1 week after and then 1 year after the direct observation study. The
      direct observation study recorded a water contact rate higher than reported by
      other investigators (3.2 contacts per person per day); however, 75% of these
      contacts were for females and consisted mainly of domestic activities occurring
      around the household. A comparison of the frequency of water contact activities
      between the direct observation and the two surveys revealed several important
      points. First, no significant differences were found between methods for routine
      water contact activities (e.g. bathing), indicating that participants were able
      to accurately self-report some types of water contact activities. Second,
      significant differences were found in the recording of water contact activities
      that took place outside the observation area, indicating that direct observation
      may under-report water contact activities in areas where contact sites are
      dispersed widely. Third, significant differences between the direct observation
      and the survey method were more common for males than for females, indicating
      that the combination of widespread water contact sites and gender-specific
      division of labour may result in under-reporting of male contacts by direct
      observation methods. In short, despite the limitations in the recording of
      duration and body exposure, the survey method may more accurately record the
      frequency of water contact activities than direct observation methods in areas of
      widely dispersed water contact sites. Hence, surveys may be more suitable for the
      unique challenges of water contact in rural areas of Brazil.

PMID- 11251906
TI  - Diagnosing visceral leishmaniasis with the recombinant K39 strip test: experience
      from the Sudan.
AB  - We compared a strip test employing recombinant K39 (rK39) antigen and protein
      A/colloidal gold as read-out agents with the rK39 ELISA for IgM and IgG
      antibodies and the direct agglutination test (DAT) using 55 sera from patients
      with parasitologically confirmed visceral leishmaniasis (VL). The rK39 strip test
      was positive in 37/55 (67%), the DAT in 50/55 (91%) at > or = 1 : 1600 cut-off
      value and in 47/55 (85%) at > or = 1 : 6400 cut-off value. The rK39-ELISA gave
      positive IgG results for all sera; those who had a positive strip test had
      significantly higher IgG levels than those with a negative strip test (31.1
      (SD=3.6) and 17.7 U/ml (SD=9.8), respectively, P < 0.0001). A total of 31/55
      (56%) sera showed a positive IgM result; of these 27 (49%) had a positive strip
      test. We tested 115 apparently cured VL patients with the strip test during
      follow-up; 68 were also tested with DAT. In the strip test, 25-43% of patients
      had a positive result at time points 3, 6, 9 and 12 months after treatment; for
      DAT (cut-off > or = 1 : 1600) these results were 67-83%. In neither test did a
      significant decrease in positivity rates occur over time (P=0.37 for the strip
      test, P=0.17 for the DAT). No correlation (P=0.33) was found between a positive
      strip test and a positive DAT result (cut-off > or = 1: 1600), indicating that
      the strip test and DAT are complementary rather than interchangeable. Of 61
      endemic controls two (3%) had a positive strip test result; both had a positive
      leishmanin skin test. The rK39 strip test has the ideal format for use in the
      field, but its sensitivity is limited; like DAT, but to a lesser extent, it
      remains positive after treatment.

PMID- 11251910
TI  - Exposure to Schistosoma mansoni infection in a rural area in Brazil. II:
      household risk factors.
AB  - A number of studies have pointed out the potential importance of the household in
      the transmission of schistosomiasis. The clustering of domestic activities
      associated with water collection, storage, and usage can result in the sharing of
      transmission sites and infective water contact behaviours. In this study, we
      employed a variance component method to estimate effects due to individual risk
      factors and shared residence on the variance in faecal egg counts during
      Schistosoma mansoni infection. A suite of covariates, which included demographic,
      socioeconomic, water supply, and water contact behaviour terms, contributed 15%
      to the variance in faecal egg counts. Shared residence alone accounted for 28% of
      the variance in faecal egg excretion. When both the suite of covariates and
      shared residence were considered in the same model, shared residence still
      contributed 22% to the variance in infection intensity. These results point to
      the importance of shared residence as a means of capturing the complex
      interrelationship between shared demographic, socioeconomic, physical
      environmental, and behavioural factors that influence transmission of
      schistosomiasis at the household level.

PMID- 11251912
TI  - The first decade of the Malawi College of Medicine: a critical appraisal.
AB  - The College of Medicine of the University of Malawi was opened in April 1991.
      Over almost a decade it has flourished in the face of economic and political
      constraints, as well as a change in the philosophy of donor support. We review
      the past, assess the present and look to the future.

PMID- 11251913
TI  - 'Complex problems have simple, easy-to-understand wrong answers.'
      [Anon]...effective communication in the practice of ultrasound.

PMID- 11251915
TI  - Nuchal translucency measurement and pregnancy outcome in karyotypically normal
      fetuses.
AB  - OBJECTIVE: The aim of the study was to evaluate the use of nuchal translucency
      measurement as a marker of adverse pregnancy outcome in karyotypically normal
      fetuses. METHODS: During the years 1995-99, nuchal translucency (NT) measurement
      was routinely offered to all women who had their dating scan in our unit. From
      the data collected, we calculated the 95th and 99th centiles of the NT for a
      given crown-rump length using regression analysis. The NT measurements were
      analyzed in relation to pregnancy outcome, especially with regards to
      miscarriage, intrauterine death and diagnosis of fetal structural abnormalities,
      after excluding chromosomal abnormalities. RESULTS: The pregnancy outcome was
      available in 6650 (89%) of the 7500 pregnancies. In fetuses with an NT over the
      99th centile, 17.8% (relative risk 12.2, 95% CI 7.2-20.8) had an adverse
      pregnancy outcome (miscarriage, intrauterine death, or termination for fetal
      abnormality) versus 1.5% for those with a normal measurement. The incidence of
      structural abnormalities, especially heart defects, was significantly increased
      in the high-NT groups. Three out of 11 fetuses with major cardiac abnormalities
      had an NT measurement over the 99th centile. The calculated relative risk for
      major heart defects in fetuses with increased NT was 33.5 (95% CI 9-123).
      CONCLUSION: In the setting of routine antenatal screening, an increased NT
      measurement is a marker of a high-risk pregnancy even in karyotypically normal
      fetuses. In addition, the increased incidence of structural abnormalities makes
      the close follow-up of these pregnancies imperative and should include
      specialized fetal echocardiography.

PMID- 11251914
TI  - Increased nuchal translucency and normal karyotype: coping with uncertainty.

PMID- 11251918
TI  - A large-scale evaluation of amnio-PCR for the rapid prenatal diagnosis of fetal
      trisomy.
AB  - OBJECTIVE: Traditional chromosome preparation from amniotic fluid samples often
      involves lengthy culture procedures in order to obtain cells for analysis.
      Multiplex quantitative fluorescent polymerase chain reaction (PCR) is a new
      molecular biological technique capable of quantifying in-situ DNA without the
      need for cell culture. Our objective was to test the reliability of PCR using
      fetal DNA from amniotic fluid (amnio-PCR) for the rapid prenatal diagnosis of the
      common trisomies. DESIGN: This was a large prospective study of 5000
      amniocentesis specimens. Multiplex quantitative fluorescent PCR was performed
      specifically for short tandem repeat sequences within chromosomes 21, 18, 13, X
      and Y. All amniocentesis samples were subsequently analyzed by traditional
      karyotyping methods. RESULTS: Amnio-PCR detected all 89 major autosomal trisomies
      in this cohort. Diagnosis of sex chromosome anomalies was accurate for cases
      involving first meiotic division nondisjunction. However, further markers were
      necessary to detect sex chromosome anomalies arising from second meiotic division
      nondisjunction, highlighting the importance of using specific markers that enable
      the quantification of both the X and the Y chromosomes simultaneously.
      CONCLUSIONS: Rapid prenatal diagnosis of trisomies 21, 18, and 13 and the sex
      chromosome anomalies using amnio-PCR is a reliable technique that aids the
      clinical management of pregnancy. The speed of the methodology will help to
      minimize the period of parental anxiety in the wait for a diagnostic test result.

PMID- 11251916
TI  - Limitations of using first-trimester nuchal translucency measurement in routine
      screening for major congenital heart defects.
AB  - OBJECTIVE: To evaluate the effectiveness of nuchal translucency (NT) measurement
      in screening for major congenital heart disease (CHD) in chromosomally normal
      fetuses. DESIGN: A population based cohort study of all women having fetal NT
      measurement at 10-14 weeks of gestation in an unselected population over a 3-year
      period. The outcome measure was the identification of major CHD in chromosomally
      normal pregnancies either antenatally or postnatally. RESULTS: Major defects of
      the heart and great arteries were identified in 26 out of 7339 pregnancies
      (prevalence 3.5 per 1000 pregnancies). Out of 26 cases, only four (sensitivity
      15.4%, 95% CI 4-35) were in the group of 258 pregnancies (3.5%) with increased NT
      of > or = 2.5 mm. The prevalence of major CHD increased from 3.1 per 1000 for NT
      < 2.5 mm to 50 per 1000 for NT > or = 3.5 mm (likelihood ratio of 14.1, 95% CI
      4.2-47.9). The positive and negative predictive values for NT > or = 2.5 mm were
      1.6% and 99.7%, respectively. CONCLUSIONS: The prevalence of major CHD in this
      study was 3.5 per 1000, suggesting that ascertainment of CHD in our study
      population was thorough. Fetuses with NT measurements > or = 3.5 mm have a
      significantly increased risk of major CHD, and this identifies a subgroup of high
      risk patients in whom early fetal echocardiography would be advocated. The low
      sensitivity of NT for major CHD in the general population, however, indicates
      that NT cannot be relied on as the sole or major screening tool for this
      condition as previously reported.

PMID- 11251919
TI  - Ultrasound assessment of the fetal foramen ovale.
AB  - OBJECTIVES: Based on the assumption that the horizontal area between the fetal
      foramen ovale valve and the atrial septum (the outlet) represents the limiting
      structure for the foramen ovale flow, our objective was to determine the normal
      size of this section during the second half of pregnancy. METHODS: One hundred
      and thirty-eight women with low-risk singleton pregnancies were examined in a
      cross-sectional study between 18 and 42 weeks of gestation. Using ultrasound
      imaging and M-mode, the area and diameter between the foramen ovale valve and the
      atrial septum were determined in a four-chamber view of the fetal heart above the
      foramen ovale limbus. The inferior vena cava cross section and right atrial width
      were also determined. RESULTS: The mean foramen ovale width increased from 3 mm
      at 18 weeks to 6 mm at term. Correspondingly, the horizontal area grew from 15 to
      50 mm2. The mean ratio between this area and the area of the inferior vena cava
      fell from 1 at 18 weeks to 0.5 at term. The ratio between the transverse width of
      the foramen ovale and the right atrium remained at average 0.45-0.50 until 32
      weeks, when a slight reduction was observed towards term. CONCLUSIONS: Normal
      values for the horizontal cross section and transverse diameter of the foramen
      ovale outlet were established for the second half of pregnancy. In particular,
      the horizontal transverse diameter and its ratio to the right atrial width are
      easy to determine, and use of these measurements is thus suggested for the
      assessment of the fetal foramen ovale.

PMID- 11251917
TI  - Relationship between fetal nuchal translucency and crown-rump length in an Asian
      population.
AB  - OBJECTIVES: To investigate the relationship between the nuchal translucency (NT)
      thickness and crown-rump length (CRL) in normal Asian fetuses during the first
      trimester. DESIGN: A prospective observational study was conducted. Ultrasound
      measurement of NT and CRL was offered in 879 consecutive Taiwanese fetuses
      between 9 weeks and 14 weeks of gestation. Regression analysis was used to
      analyze the relationship between the NT thickness and CRL. Fetal sex was also
      considered in the analysis. The distribution of multiple of median (MoM) values
      of the NT measurements with CRL in 10-mm intervals and the 95th centile of MoM
      were also calculated. RESULTS: The present study shows that NT measurements
      increase with increasing CRL. A fixed cut-off point through the first trimester
      is not appropriate. The NT thickness has no relationship with fetal sex.
      Expressing the NT thickness by MoM values provides a simple method for clinical
      practice. CONCLUSIONS: The present study offers normative data of the fetal NT
      thickness in an Asian population, which may improve the performance of NT
      measurement during the first-trimester as a screening tool for chromosomal
      aberrations or other congenital abnormalities in the first trimester.

PMID- 11251921
TI  - The development of the fetal penis--an in utero sonographic evaluation.
AB  - OBJECTIVE: To establish a nomogram for fetal penile length during gestation.
      DESIGN: A prospective, cross-sectional study of normal singleton pregnancies.
      SUBJECTS: Four hundred and nineteen male fetuses between 14 and 38 weeks were
      studied. METHODS: Measurements of fetal penis length were performed by high
      resolution transvaginal ultrasonography between 14 and 17 weeks of gestation, and
      by transabdominal ultrasonography beyond 18 weeks of gestation. RESULTS: Adequate
      penile length measurements were obtained in all 419 fetuses. Penile length as a
      function of gestational age was expressed by the regression equation: (square
      root) penile length (mm) = 0.277 + 0.121 x gestational age (weeks). The
      correlation coefficient, r = 0.967 was found to be highly statistically
      significant (P < 0.0001). The normal mean and the 90% prediction limits were
      defined. During the study period, we identified three fetuses with abnormalities
      involving penile development. Using the above reference data range, it has been
      shown that their penile length was below the lower limit. CONCLUSIONS: The
      present data provide a normal range of fetal penile length from early stages of
      gestation that may allow intrauterine assessment of the development of the male
      external genitalia.

PMID- 11251920
TI  - Longitudinal survey of blood flow at three different locations in the middle
      cerebral artery in normal fetuses.
AB  - OBJECTIVES: To assess vascular impedance at three different locations in the
      middle cerebral artery (MCA) in normal fetuses throughout gestation. MATERIALS
      AND METHODS: Uncomplicated singleton pregnancies at 15-40 weeks' gestation in
      which Doppler surveys of both MCAs could be obtained were recruited. The
      pulsatility index (PI) and resistance index (RI) of the proximal, mid and distal
      sites of both MCAs were measured. The five gestation periods at which the Doppler
      surveys were performed were (i) 15-19 completed weeks; (ii) 20-24 completed
      weeks; (iii) 25-29 completed weeks; (iv) 30-34 completed weeks; (v) 35-39
      completed weeks. RESULTS: A total of 42 fetuses were recruited. The average PI/RI
      values of the proximal, mid and distal MCA were 1.61/0.82, 1.77/0.82, and
      1.84/0.84, respectively. The PI value of the proximal MCA was lower than that of
      the mid and distal MCA. The PI values of the mid and distal MCA showed no
      difference. The RI value of the MCA from the three locations also showed no
      difference. The PI/RI values of MCA for each gestational phase were: (i)
      1.81/0.87; (ii) 1.79/0.86; (iii) 1.78/0.86; (iv) 1.70/0.81; (v) 1.62/0.77,
      respectively. Decreased PI/RI values were observed after 30 weeks' gestation.
      CONCLUSIONS: The PI values of the proximal MCA are lower than those of the mid
      and distal MCA. A marked decrease in PI/RI values was observed after 30 weeks'
      gestation.

PMID- 11251923
TI  - The characterization of common ovarian cysts in premenopausal women.
AB  - OBJECTIVES: The evaluation of the predictive value of transvaginal ultrasound in
      the assessment of benign adnexal pathology in premenopausal women, based on the
      recognition of characteristic morphologic patterns particular to endometriotic
      and dermoid ovarian cysts. METHODS: This was a prospective study. All
      premenopausal women undergoing surgery for a suspected ovarian cyst underwent a
      transvaginal ultrasound examination in the week prior to surgery. Between June
      1997 and January 2000, 132 women underwent surgery for a suspected ovarian
      endometrioma or dermoid cyst. The endpoints were either the direct visualization
      of the cyst wall and contents at surgery, or the histologic evaluation of removed
      tissues. RESULTS: Of 83 suspected endometriomas (11 bilateral), 80 were confirmed
      at surgery and of 68 suspected benign cystic teratomas (eight bilateral), 66 were
      confirmed by histology. The positive predictive value of transvaginal
      ultrasonography for the diagnosis of endometrioma and dermoid cysts was 96.4% and
      97.1%, respectively. The false positive rates were 3.8% and 3.0%, respectively.
      There were no malignancies in either group. CONCLUSIONS: Based on the recognition
      of characteristic ultrasound patterns alone, the positive predictive value of
      transvaginal ultrasonography for the diagnosis of these common, benign cysts in
      premenopausal women is very high and can be used reliably to select women for
      appropriate surgery.

PMID- 11251930
TI  - Ultrasound-guided needle aspiration of a fetal choledochal cyst.

PMID- 11251924
TI  - Saline contrast sonohysterography in the preoperative assessment of benign
      intrauterine disorders.
AB  - OBJECTIVES: To assess the value of saline contrast sonohysterography (SCSH) in
      the preoperative evaluation of benign intrauterine lesions. DESIGN: Patients
      presenting with abnormal bleeding related to benign uterine pathologies and
      scheduled for surgical treatment were prospectively enrolled in a study conducted
      between 1 January 1996 and 31 December 1997. SCSH was first carried out with the
      intention of establishing further surgical management (hysterectomy or
      hysteroscopy). The end point of the study was to compare the surgical option
      ultimately carried out with the one decided after SCSH. In addition, size and
      location of intrauterine lesions determined by SCSH were compared with those
      issued from surgical records. Similarly, pathologic results were juxtaposed to
      SCSH diagnosis. Statistical analysis used non-parametric and correlation tests.
      RESULTS: Two hundred and thirty-three patients were included in the study, 39.5%
      of whom were postmenopausal. SCSH was consistently effective in the choice of the
      best surgical method, because no hysterectomy was required when an operative
      hysteroscopy was indicated on SCSH data. Similarly, only one patient treated by
      hysterectomy (5.8%) could have undergone a more conservative approach. But this
      patient had a genital prolapse, and thus hysterectomy was a part of the
      treatment. SCSH correlated well with surgery for the location and size of
      intrauterine lesions (P < 0.001). SCSH was accurate in the diagnosis of polyps
      and submucous myomas (sensitivity 85.7%, specificity 95.4%). CONCLUSIONS: SCSH
      appears an important tool for preoperative assessment of benign intrauterine
      pathologies. It should be used in the selection of patients that should be
      scheduled for an operative hysteroscopy.

PMID- 11251927
TI  - A case of body stalk anomaly at 10 weeks of gestation.
AB  - We describe a case of body stalk anomaly which was diagnosed at 10 weeks of
      gestation on a dating scan. The fetus was visualized within the exocelomic cavity
      outside an apparently intact amniotic membrane. The fetus displayed multiple
      anomalies characteristic of body stalk syndrome including a skull and brain
      defect, abdominal wall defect, kyphoscoliosis and gross deformities of the lower
      limbs. These findings do not support early amniotic membrane rupture as the
      primary event in the pathogenesis of body stalk anomaly and indicate that the
      exocelomic location of the fetus may actually be one of the features of this
      complex developmental anomaly.

PMID- 11251922
TI  - Fetal urine production and accuracy when estimating fetal urinary bladder volume.
AB  - OBJECTIVES: The volume of the fetal urinary bladder can be estimated by measuring
      bladder diameters on an ultrasound image. The calculated urine production rate
      might reflect the fetal status in compromised pregnancies. The aim of this study
      was to assess the fetal urine production rate and the accuracy of measurements of
      diameters and volumes of the bladder. DESIGN: Urine production rate and the
      variability in volume measurement error were assessed by ultrasound examinations
      of fetal bladder images documented on videotapes. In material comprising 101
      longitudinal and 90 transverse bladder images, the variability (SD) in distance
      measurement error was estimated for the bladder diameters. Using this SD, the
      variability in volume measurement error in the selected bladder image was also
      calculated. RESULTS: The urine production rate for fetuses of 20, 25, 30, 35 and
      40 weeks is 4.2, 12.1, 22.7, 36.1 and 52.2 mL/h, respectively. The SD for volume
      measurement error when selecting bladder images with a volume of 5, 10, 20, 30
      and 40 mL is 17.3%, 13.6%, 11.8%, 11.2% and 10.9% of the actual volume,
      respectively. The corresponding SD when measuring the volume of selected bladder
      images accounted for 3.7-2.0%. CONCLUSIONS: The urine production rate presented
      here is in parity with recent previous reports. We distinguish between different
      kinds of measurement error. The variability was mostly related to the selection
      of appropriate bladder image, whereas measurement of the selected bladder image
      accounted for only a minor part of the resulting variability.

PMID- 11251926
TI  - Twin reversed arterial perfusion sequence in twin-to-twin transfusion syndrome
      after the death of the donor co-twin in the second trimester.
AB  - A twin-to-twin transfusion syndrome was diagnosed in a monochorionic-diamniotic
      pregnancy at 18 weeks' gestation without any malformation, especially heart
      defect. In spite of the aggressive treatment (serial amnioreduction, digoxin
      treatment) the donor twin died at 25 weeks and twin reversed arterial perfusion
      (TRAP) sequence developed and was documented by Doppler ultrasound. In the TRAP
      twin, the route of the reversed blood flow from the umbilical arteries was as
      follows: descending aorta, aortic arch, ascending aorta, aortic valve, left
      ventricle, mitral valve, left atrium, foramen ovale, right atrium, inferior vena
      cava, ductus venosus; and back to the placenta through the umbilical vein. After
      a 12-h observation period the twin reversed arterial perfusion sequence
      disappeared. During this period ultrasound and fetal blood sampling revealed no
      sign of fetal anemia or disseminated intravascular coagulation in the surviving
      twin. Based on our observations, we propose, that the death of one of the twins
      in monochorionic pregnancy can result in twin reversed arterial perfusion
      sequence, which is an ultimately rare phenomenon in the second trimester. To our
      knowledge, this is the first reported case of twin reversed arterial perfusion
      sequence subsequent to the intrauterine demise of one twin in twin-to-twin
      transfusion syndrome in which the TRAP-twin had no cardiac malformation.

PMID- 11251929
TI  - Congenital microvillous inclusion disease presenting as antenatal bowel
      obstruction.
AB  - Prenatal ultrasound has led to confidence in the antenatal diagnosis of
      intestinal obstruction allowing counseling and birth planning. We describe a male
      infant of a diabetic mother who had an antenatal diagnosis of distal bowel
      obstruction. This baby was subsequently found not to have bowel obstruction, but
      a congenital enteropathy - microvillous inclusion disease. The antenatal scans
      had demonstrated polyhydramnios as well as multiple fluid-filled dilated loops of
      bowel in the fetal abdomen. To our knowledge, similar prenatal ultrasound
      findings have not been previously described in this condition. The baby was
      delivered in a pediatric surgical center and postnatally there was no evidence of
      bowel obstruction either clinically or on abdominal X-ray. This baby initially
      fed well, but became collapsed and acidotic on his third day, having lost 26% of
      his birth weight due to excessive stool loss. The diagnosis of microvillous
      inclusion disease was made by electron microscopy of a small bowel biopsy.
      Congenital microvillous inclusion disease is a very rare inherited enteropathy
      with high mortality and morbidity. This condition, and other enteropathies,
      should be considered in cases in which antenatally diagnosed bowel obstruction is
      not confirmed after birth.

PMID- 11251928
TI  - Pena-Shokeir phenotype with variable onset in three consecutive pregnancies.
AB  - The Pena-Shokeir phenotype represents an autosomal recessive syndrome
      characterized by neurogenic arthrogryposis, facial anomalies and pulmonary
      hypoplasia. Prenatal diagnosis of this disease has been reported prospectively
      and in cases with positive family history. We describe here a patient who has had
      three consecutive pregnancies affected by the Pena-Shokeir syndrome. In these
      pregnancies, the onset of the arthrogryposis varied between the 12th and the 18th
      week of gestation. Therefore, the possibility of a variable chronological
      development of the main diagnostic feature of the syndrome, arthrogryposis, has
      to be taken into proper consideration while counseling families with a positive
      history for the Pena-Shokeir phenotype.

PMID- 11251925
TI  - Real-time intraoperative ultrasound guidance: the transrectal approach.
AB  - OBJECTIVE: To assess the role of real-time transrectal ultrasound guidance in
      complicated gynecologic procedures. DESIGN: In 1998-99, real-time guidance with
      transrectal ultrasound was utilized in our department to assist the gynecologic
      surgeon in two procedures: completing the evacuation of the uterine cavity after
      identification of uterine wall perforation during first trimester termination of
      pregnancy, and drainage of infected vaginal vault hematoma following
      hysterectomy. RESULTS: The technique was applied for 11 patients, six abortions
      and five infected hematomas. All the procedures were completed without any
      further complications and the patients were discharged on the following day.
      Follow-up was uneventful. CONCLUSIONS: On-line intraoperative transrectal
      ultrasound can effectively provide real-time assistance to the gynecologic
      surgeon during complicated pelvic procedures.

PMID- 11251931
TI  - Picture of the month. Adenomyosis: power Doppler findings.

PMID- 11251934
TI  - Establishing an endovascular abdominal aortic program--decisions, decisions,
      decisions: The London Health Sciences Centre experience.
AB  - The endovascular repair of abdominal or thoracic aortic aneurysms is an
      alternative approach to conventional repair in the compromised patient. Although
      the long-term efficacy of these procedures has yet to be proved, there is growing
      interest among vascular surgeons and interventional radiologists throughout North
      America and Europe in the more frequent use of this technique. Starting an
      endovascular program necessitates extensive cooperation of the interdisciplinary
      vascular team. Decisions regarding patient selection, equipment, supplies, staff
      education, and the location of the procedure must be based on sound principles.
      This article demonstrates how a program can be planned, implemented, and
      evaluated by the use of a "decision tree." The experience of the London Health
      Sciences Centre will be used as a benchmark in the discussion of relative merits
      of branch points in program development. The article gives persons contemplating
      a program a structured process in decision making to avoid potential pitfalls.

PMID- 11251936
TI  - Standards of care for venous leg ulcers: compression therapy and moist wound
      healing.
AB  - Venous ulcers are the most common type of cutaneous ulceration of the lower
      extremity, accounting for 70% to 90% of all cases. Despite recent advances in
      treatment and the development of new modalities, the current standard of care
      remains compression therapy in combination with appropriate moist wound care
      principles. The physiology of the venous system and the pathophysiology of venous
      disease leading to ulceration are described. A review of the use of gradient
      compression therapy is provided, including a discussion of several types. The
      history of moist wound healing and the use of hydrocolloids also are included. It
      is essential for the vascular nurse to be well versed in the areas of compression
      therapy and moist wound principles as the most effective treatment for venous
      ulcers at this time.

PMID- 11251933
TI  - Carotid artery dissection.
AB  - Carotid artery dissection (CAD) is one of the more common causes of stroke in
      persons younger than 50 years. In this age group and in older persons, CAD is
      most often associated with trauma. Significant morbidity can be a consequence of
      CAD, particularly a stroke or other permanent neurologic deficit. Because stroke
      is the third leading cause of death in the United States, attention has focused
      in the past decade on understanding the phenomenon of dissection of the carotid
      artery. This article presents a review of the risk factors associated with CAD,
      the role of the nurse as a provider of care for these persons, and the approaches
      to prevent or limit disability related to CAD, the ultimate goal of patient care.
      Nurses play a crucial role in the detection of CAD and in the prevention of
      strokes or other neurologic disabilities through recognition of persons at risk,
      assessment for early signs and symptoms, and implementation of prophylactic
      measures. Because more than half of persons with CAD have cerebral ischemia,
      thrombolytic, anticoagulant, and antiplatelet regimens have evolved to limit the
      development of a thromboembolic event associated with dissection. The
      administration of these agents, the monitoring for their effectiveness, and the
      education of patients receiving them are fundamental aspects of care.

PMID- 11251935
TI  - Dysphagia lusoria: a case study.
AB  - Dysphagia lusoria is described in the literature as difficulty swallowing because
      of a "jest of nature." The "jest of nature" is a birth defect encompassing any
      aortic root vascular anomaly that causes esophageal dysphagia. Persons with
      dysphagia lusoria can be categorized according to their specific subclavian
      anomaly (ie, depending on the presence of an aneurysm, occlusive disease, or
      esophageal compression). All patients with this anomaly have an aberrant
      subclavian artery in a transposed position that courses posterior to the
      esophagus. The operative approach to repair this condition has been
      controversial. An extrathoracic approach is documented as superior to a repair
      involving thoracotomy because there is decreased rate of complications that may
      be associated with a thoracotomy and greater visibility of the subclavian and
      carotid artery. This case study describes a 25-year-old woman with dysphagia
      lusoria related to an aberrant right subclavian artery. The report includes a
      literature review and describes the perioperative approach and nursing care. The
      use of the preadmission and same-day admission services are supported as is an
      extrathoracic surgical approach. At follow-up this patient reported no symptoms
      of dysphagia and showed no evidence of esophageal compression confirming that
      persons with symptomatic dysphagia lusoria can be managed with positive long-term
      results.

PMID- 11251937
TI  - Brief research report.

PMID- 11251938
TI  - Meningioma.

PMID- 11251939
TI  - Risk reduction endpoints should be part of the design of adjuvant therapy
      clinical trials for patients with melanoma. A commentary.

PMID- 11251940
TI  - 2-(fluorine-18)fluoro-2-deoxy-D-glucose positron emission tomography in the
      detection and staging of malignant lymphoma. A bicenter trial.
AB  - BACKGROUND: The authors undertook a prospective evaluation of the clinical value
      of 2-fluoro [18-]-2-deoxyglucose positron emission tomography (FDG-PET) in the
      detection and staging of malignant lymphoma compared with computed tomography
      (CT) and bone marrow biopsy (BMB). METHODS: Fifty-two consecutive patients with
      untreated malignant lymphoma were evaluated prospectively in a bicenter study.
      FDG-PET, CT, and BMB were performed for investigating lymph node/extranodal
      manifestations and bone marrow infiltration. Thirty-three percnt of the
      discrepant results were verified by biopsy, magnetic resonance imaging, or
      clinical follow-up (range, 4-24 month). RESULTS: Altogether, 1297 anatomic
      regions (lymph nodes, organs, and bone marrow) were evaluated. FDG-PET and CT
      scans were compared by receiver operating characteristic (ROC) curve analysis.
      The area under the ROC curve were as follows: lymph nodes, 0.996 (PET) and 0.916
      (CT); extranodal, 0.999 (PET) and 0.916 (CT); supradiaphragmatic, 0.996 (PET) and
      0.905 (CT); and infradiaphragmatic, 0.999 (PET) and 0.952 (CT). In these
      analyses, FDG-PET was significantly superior to CT (P < 0.05), except in
      infradiaphragmatic regions, in which the two methods produced equivalent results.
      In detecting bone marrow infiltration, FDG-PET was superior to CT and was
      equivalent to BMB. In 4 of 52 patients (8%), FDG-PET led to an upstaging and a
      change of therapy. CONCLUSIONS: Noninvasive FDG-PET is very accurate in the
      staging of malignant lymphoma. Compared with standard staging modalities (CT and
      BMB), PET was significantly superior and led to changes in the therapy regimen
      for 8% of patients.

PMID- 11251941
TI  - Distinct T-cell clonal expansion in the vicinity of tumor cells in plasmacytoma.
AB  - BACKGROUND: Although various clinical observations suggested that myeloma cell
      growth might be modulated by the immune system, evidence supporting the in situ
      immunogenicity of myeloma cells remains scarce. The authors reasoned that if
      there is any specific T-cell/tumor cell interaction in myeloma, it is most likely
      reflected in the T-cell population in the vicinity of the tumor cells. METHODS:
      The authors used a molecular method to compare the T-cell populations in the
      vicinity of tumor cells with those in the peripheral blood in patients with
      plasmacytomas and multiple myeloma. RESULTS: Six patients were studied. When
      compared with the peripheral blood from the corresponding patients, T cells in
      the vicinity of tumor cells in five of the six patients showed significant
      contraction of the T-cell receptor (TCR) Vbeta repertoire. In addition to this,
      the T cells isolated from the sites of the tumor cells from four of these five
      patients also demonstrated significant increase in the number of TCR Vbeta gene
      families with restricted number of CDR3 size peaks and loss of the normal CDR3
      size gaussian distribution pattern. These findings were observed in patients who
      experienced recurrence after allogeneic stem cell transplantation and also in
      those who had autologous stem cell transplant. They also were found in previously
      untreated myeloma patients. In all six patients, distinct TCR Vbeta recurring
      transcripts indicative of a T-cell clonal expansion were found in the vicinity of
      the tumor cells and either absent or detected at only a low frequency in the
      peripheral blood. CONCLUSIONS: Our results provide evidence for an in situ local
      T-cell clonal expansion in the vicinity of tumor cells and support the presence
      of specific T-cell/tumor cell interaction in myeloma.

PMID- 11251942
TI  - G-CSF induces elevation of circulating CA 15-3 in breast carcinoma patients
      treated in an adjuvant setting.
AB  - BACKGROUND: Cancer antigen 15-3 (CA 15-3), a circulating marker that determines
      secreted products of the polymorphic MUC1 gene, has been established as a
      convenient tool for monitoring breast carcinoma patients. METHODS: The authors
      investigated alterations of soluble CA 15-3 in 57 postoperative breast carcinoma
      patients while they were receiving intensified adjuvant chemotherapy with
      granulocyte colony stimulating factor (G-CSF) support; 26 patients had American
      Joint Committee on Cancer (AJCC) Stage II, and 31 patients had AJCC Stage III
      breast carcinoma. Serial CA 15-3 values recorded thoughout the treatment were
      compared with baseline values, analyzed for correlation with hematologic and
      biochemical parameters, and compared with clinicopathologic characteristics and
      patient outcome. At a median follow-up time of 32 months, 47 of these patients
      remained relapse-free. RESULTS: A twofold increase of CA 15-3 was detected at the
      end of the second week of treatment, remained significantly elevated in most
      patients at above the cutoff level of 30 U/mL throughout the treatment period (P
      < 0.0001), and subsided to pretreatment values 1-2 months after treatment
      cessation. CA 15-3 values were found to be associated strongly with absolute
      neutrophil count, serum lactate dehydrogenase, and alkaline phosphatase. The
      median values and the kinetics of tumor markers did not differ over time in
      regard to hormonal receptor status and disease recurrence. CONCLUSIONS: These
      data provide strong evidence that G-CSF administration can induce elevation of CA
      15-3 and indicate that false-positive results should be considered when
      evaluating CA 15-3 in patients who are receiving G-CSF. It is speculated that
      this phenomenon occurs through the induction of MUC1 antigen of unknown origin by
      G-CSF. Experimental investigation of this clinical observation is warranted.

PMID- 11251943
TI  - Neoadjuvant therapy for patients with locally advanced gastric carcinoma with
      etoposide, doxorubicin, and cisplatinum. Closing results after 5 years of follow
      up.
AB  - BACKGROUND: The intent to curatively treat patients with gastric carcinoma is
      based on complete surgical resection of the primary tumor and its lymphatic
      drainage. Postoperative adjuvant chemotherapy has failed to show a significant
      prognostic advantage for these patients. Preoperative chemotherapy, based on
      promising results in the treatment of patients with disease in primarily
      unresectable stages, is still being evaluated for those with locally advanced
      gastric carcinoma. Most published studies still lack adequate staging methods,
      and long term results of this treatment modality are not known at present.
      METHODS: In a Phase II study, a series of 42 patients with locally advanced
      gastric carcinoma (International Union Against Cancer Stages IIIA, IIIB, and IV)
      initially were staged with endoscopy, with endoscopic ultrasound to establish the
      clinical tumor classification, with computed tomography scans to rule out tumor
      infiltration of adjacent organs and to detect distant metastases, and with
      surgical laparoscopy to exclude occult peritoneal carcinomatosis. Three or four
      planned cycles of neoadjuvant chemotherapy with etoposide, doxorubicin, and
      cisplatinum were given prior to total gastrectomy. RESULTS: After a complete
      follow-up of at least 5 years, there was a median survival of 19.1 months for all
      patients. Only patients who underwent a complete surgical tumor resection
      appeared to have a survival benefit, with a median survival of 28.4 months. A
      superior survival rate was seen in patients who had a major clinical response to
      chemotherapy, with a median survival of 45 months. CONCLUSIONS: Phase III studies
      comparing results from patients who undergo neoadjuvant chemotherapy followed by
      surgery with results from patients who undergo surgery alone should stress the
      value of adequate pretherapeutic staging and must be accompanied by studies of
      potential methods for predicting tumor response.

PMID- 11251944
TI  - De novo establishment and cost-effectiveness of Papanicolaou cytology screening
      services in the Socialist Republic of Vietnam.
AB  - BACKGROUND: Cervical carcinoma is the leading cause of cancer-related death among
      women in the developing world. The absence of cervical screening in Vietnam and
      other developing countries is due in large part to the perceived expense of
      implementing Papanicolaou cytology screening services, although, to the authors'
      knowledge, the cost-effectiveness of establishing such services has never been
      studied in a developing country. METHODS: Using decision analytic methods, the
      authors assessed cost-effectiveness of Pap screening from a societal perspective
      in Vietnam, the world's 9th most populous developing country (estimated 1999
      population, 79 million). Outcomes measured included life expectancy, cervical
      carcinoma incidence, cost per woman, and cost-effectiveness. RESULTS: Total costs
      to establish a nationwide 5-year interval Pap screening program in Vietnam will
      average less than $148,400 annually during the 10-year time period assumed
      necessary to develop the program and may be considerably lower if only high risk
      geographic areas are targeted. Maintenance costs will average less than $0.092
      annually per woman in the target screening population. Assuming 70% program
      participation, cervical carcinoma incidence will decrease from 26 in 100,000 to
      14.8 in 100,000, and cost-effectiveness will be $725 per discounted life-year.
      Several assumptions used in this analysis constitute biases against the
      effectiveness of Pap screening, which in reality may be significantly more cost
      effective than reported here. CONCLUSIONS: Contrary to widespread belief, Pap
      screening in developing countries such as Vietnam is extraordinarily inexpensive
      and appears to be cost-effective. Because prospects are uncertain regarding
      useful alternatives to the Pap test, the evidence-based argument for establishing
      conventional Pap screening services in developing countries such as Vietnam is
      compelling. Population-based conventional Pap screening services have been
      established de novo in Vietnam and are now operational.

PMID- 11251945
TI  - Induction paclitaxel and carboplatin for patients with head and neck carcinoma.
      Analysis of 62 patients treated between 1994 an 1999.
AB  - BACKGROUND: After standard therapy for advanced head and neck carcinoma, 5-year
      survival rate is less than 50%. Our purpose was to develop a new treatment for
      advanced head and neck carcinoma by using preoperative chemotherapy. Long term
      efficacy and toxicity of induction paclitaxel and carboplatin is reported here.
      METHODS: Between 1994 and 1999, 62 consecutive patients with newly diagnosed head
      and neck carcinoma were treated with paclitaxel and carboplatin induction
      chemotherapy. Chemotherapy was administered every 21 days with 3 courses of
      paclitaxel (150-265 mg/m(2)) and carboplatin at a dose calculated using the
      Calvert formula area under the curve of 7.5. Patients who achieved complete or
      partial response at the primary received definitive radiation to the primary
      tumor and those with lymph node disease received neck dissection followed by
      radiation to the regional lymph nodes. Nonresponders received standard resection
      of primary tumor and draining lymph node basin followed by radiation. RESULTS:
      Sixty-two consecutive patients were treated. Seventy-four percent had Stage IV
      (according to the 5th edition of American Joint Committee on Cancer Staging
      manual) disease. The median duration of follow-up from initiation of chemotherapy
      was 64 weeks (range, 1-272 weeks). Overall complete plus partial response rate
      was 41 of 62 (66%). Responses were observed at all anatomic sites: oropharynx 20
      of 33 (61%); hypopharynx 8 of 12 (67%); and larynx 13 of 17 (76%). Kaplan-Meier
      estimates of overall survival (OS), at 230 weeks, were significantly better in
      Stage IV oropharynx/hypopharynx responders than nonresponders (55% vs. 27%; P =
      0.04). Of the variables evaluated in multivariate models, response at the primary
      tumor and lymph nodes were associated with improved disease free survival and OS.
      Organ preservation was achieved in 28 of 62 (45%) of patients at all anatomic
      sites: oropharynx 39%, hypopharynx 42%, larynx 59%. Seventeen of 28 (61%)
      patients had their primary organ site preserved for a mean duration of 78 weeks
      (range, 13-238 weeks). CONCLUSIONS: Induction paclitaxel and carboplatin was well
      tolerated. The response rate was encouraging considering most patients were Stage
      IV. Chemotherapy response identified a group with improved prognosis. Organ
      preservation was possible at all anatomic sites.

PMID- 11251946
TI  - Risk factors for distant recurrence of hepatocellular carcinoma in the liver
      after complete coagulation by microwave or radiofrequency ablation.
AB  - BACKGROUND: In patients with hepatocellular carcinoma (HCC), recurrences in the
      distant liver often are observed after curative treatment. Microwave coagulation
      therapy (MCT) and radiofrequency ablation (RFA) have been developed as less
      invasive alternatives than surgical resection for small HCCs. In the current
      study, risk factors for distant recurrence of HCC were analyzed in patients in
      whom complete coagulation was achieved. METHODS: Ninety-two patients with HCCs <
      3 cm in greatest dimension were treated by MCT or RFA percutaneously or
      laparoscopically. Eighty-four patients in whom complete coagulation was achieved
      without recurrence in the same subsegment as the primary nodule were included in
      this study. Distant recurrences were observed in 22 patients. Fifteen possible
      risk factors for a distant recurrence were analyzed. RESULTS: When comparing the
      patients with a recurrence of HCC nodules in the remnant liver to those without
      recurrence, the authors observed a statistically significant difference only in
      serum alpha-fetoprotein. The distant recurrence-free survival was analyzed by the
      Kaplan-Meier method. A statistically significant difference was observed in
      hepatitis C virus (HCV) infection as an etiopathic agent of underlying liver
      diseases (P < 0.005) and in the number of the primary HCC nodules (P < 0.05, log
      rank test). A multivariate stepwise Cox hazard model revealed that HCV infection
      and the number of primary HCC nodules were statistically independent risk
      factors. CONCLUSIONS: Patients who had more than two HCC nodules accompanied by
      HCV infection had a high incidence of recurrence of HCC in the remnant liver,
      even when coagulation by microwave or ablation by radiofrequency was complete.

PMID- 11251947
TI  - Impact of diabetes mellitus on the prognosis of patients with hepatocellular
      carcinoma.
AB  - BACKGROUND: The majority of patients with hepatocellular carcinoma (HCC) have
      coexisting cirrhosis or chronic hepatitis, often complicated by diabetes
      mellitus. In the current study, the authors evaluated the impact of diabetes
      mellitus on the prognosis of patients with HCC. METHODS: Among 581 patients with
      HCC who had been diagnosed and treated between 1990 and 1999, survival was
      compared between those patients with and those patients without diabetes
      mellitus. The rate of disease recurrence after treatment also was analyzed.
      RESULTS: Ninety-two patients (15.8%) had diabetes mellitus. There was no
      significant difference with regard to patient characteristics (i.e., age, gender,
      or alcohol intake) or liver function between those patients with and those
      patients without diabetes mellitus. No differences were observed in survival
      between patients with diabetes mellitus and patients without it. Among the 195
      patients with a solitary HCC lesion measuring < or = 3 cm in greatest dimension,
      the survival of the 32 patients with diabetes mellitus was significantly poorer
      than that of the 163 patients without diabetes mellitus (P = 0.0273), despite no
      apparent difference in liver function between the 2 groups. On multivariate
      analysis, diabetes mellitus was found to be an independent factor predicting
      lower survival after treatment (P = 0.0077) among patients with a solitary HCC
      lesion measuring < or = 3 cm in greatest dimension. No difference in the rate of
      recurrence was observed between the two groups in all the patients and in those
      patients with a solitary HCC lesion measuring < or = 3 cm in greatest dimension.
      CONCLUSION: The results of the current study indicated that the presence of
      diabetes mellitus worsens the prognosis of patients with a solitary HCC lesion
      measuring < or = 3 cm in greatest dimension; it appears to impact prognosis in
      patients with HCC when HCC is treatable, based on the size and the number of
      lesions. However, diabetes mellitus did not appear to affect the prognosis in the
      general population of patients with HCC. Based on the current study data,
      diabetes mellitus does not appear to modify the progression of HCC and its
      recurrence after treatment, but it does appear to worsen the prognosis of
      patients with HCC by means of a rapid decline in remnant liver function caused by
      repeated treatment of HCC.

PMID- 11251948
TI  - Transforming growth factor-beta1 level correlates with angiogenesis, tumor
      progression, and prognosis in patients with nonsmall cell lung carcinoma.
AB  - BACKGROUND: Transforming growth factor-beta1 (TGF- beta1) is a multifunctional
      factor and is known to affect tumor growth in malignant tumors. The effects of
      TGF-beta1 on angiogenesis, stromal formation, and immune function suggest its
      possible involvement in tumor progression. The authors examined whether TGF-beta1
      levels may be correlated with angiogenesis, clinicopathologic factors, and
      survival in patients with surgically resected lung carcinoma. METHODS: TGF-beta1
      protein was extracted from 53 nonsmall cell lung carcinoma tissue samples (19
      squamous cell carcinomas, 33 adenocarcinomas, and 1 adenosquamous cell
      carcinoma), and its level was measured by enzyme-linked immunosorbent assay. To
      assess tumor angiogenesis, microvessel density (MVD) was determined by CD31
      immunostaining. RESULTS: The protein level of TGF-beta1 was 289 picograms per
      milligram of protein (pg/mg protein), ranging from 94 pg/mg protein to 584 pg/mg
      protein. The TGF-beta1 protein level was significantly higher in patients with
      lymph node metastasis compared with patients who were without lymph node
      metastasis (P = 0.02), and the TGF-beta1 protein level was significantly higher
      in patients with Stage III disease (TNM classification) compared with patients
      who had Stage I and II disease (P = 0.03). There was no significant correlation
      between the TGF-beta1 protein level and any of the other clinicopathologic
      factors that were considered. A significant positive correlation between TGF
      beta1 protein level and MVD was noted (P < 0.01). Furthermore, in patients with
      adenocarcinoma, a significant correlation between TGF-beta1 protein level and
      prognosis was detected by multivariate analysis (P = 0.028). CONCLUSIONS: TGF
      beta1 seems to affect tumor angiogenesis and to play an important role in tumor
      progression in patients with nonsmall cell lung carcinoma. Furthermore, the TGF
      beta1 protein level may be an independent predictor of survival in patients with
      adenocarcinoma of the lung.

PMID- 11251949
TI  - Activity, expression, and transcription rate of the cathepsins B, D, H, and L in
      cutaneous malignant melanoma.
AB  - BACKGROUND: Increased activity of the protease cathepsin B has been demonstrated
      in many tumor cells. A correlation of cathepsin B activity and metastatic
      potential of melanoma has been well established. METHODS: The cathepsins B, D, H,
      and L were evaluated in normal skin, nevi, and melanoma samples to obtain
      information about their role and their regulation in melanoma. The authors
      localized specific proteolytic activity with histochemistry, cathepsin protein
      immunohistochemistry, and mRNA with in situ hybridization. RESULTS: Activities
      and immunoreactivities of the cathepsins B and L were found to be increased in
      all melanocytic lesions. However, the staining for the corresponding mRNA levels
      was elevated only in melanomas. Cathepsin D protein and mRNA were expressed to a
      higher degree only in the dysplastic nevus and in melanomas. The increase was due
      to tumor cells and cells of the surrounding tissue. Cathepsin H activity,
      immunoreactivity, and mRNA appeared to be correlated inversely with the invasive
      potential of the lesion. CONCLUSIONS: It may be relevant for the malignant
      potential of the lesion whether the increase in activity is accompanied by an
      increase in the mRNA level. Two different mechanisms-the existence of different
      mRNAs and the higher transcription rate of the cathepsin gene-have been proposed
      for the regulation of cathepsin B activity in tumor cells. The current data
      suggest that, depending on the thickness of the melanoma, cathepsin activity is
      regulated by different mechanisms. The up-regulation of cathepsin gene
      transcription appears to be characteristic for more invasive tumor cells.

PMID- 11251950
TI  - Identification of higher risk thin melanomas should be based on Breslow depth not
      Clark level IV.
AB  - BACKGROUND: There is good prognostic correlation for the two microstaging
      systems, Breslow depth and Clark level, commonly used to stage melanomas. Many
      investigators have reported that Breslow depth is the superior microstaging
      method. Although Clark level has been dropped from most of the proposed American
      Joint Committee on Cancer (AJCC) melanoma staging system, the AJCC system still
      includes Clark Level IV as a criterion for upstaging thin melanomas. The authors
      sought to determine whether this is appropriate, based on melanoma patient data
      in the Duke Comprehensive Cancer Center database. METHODS: Of the 8833 patients
      registered between January 1, 1970 and December 31, 1995, complete data on
      Breslow depth and Clark level was available for 4560 patients who were without
      nodal or metastatic disease at presentation. Ten-year survival was measured from
      the date of excision of the primary tumor until death from melanoma and analyzed
      using Kaplan-Meier and Cox proportional hazard methodologies. RESULTS: When
      analyzed separately, both increased Breslow thickness and Clark level correlated
      with shorter survival times. During subgroup analysis, Breslow thickness remained
      a significant prognostic indicator of survival at Clark Levels III and IV.
      Conversely, at narrow levels of Breslow thickness (i.e., 0-0.75 mm, > 0.75 -1.0
      mm, > 1.0-1.5 mm) survival times were indistinguishable between Clark Levels III
      and IV. For the broader Breslow thickness interval of 0-1.0 mm, a barely
      significant difference between Clark Levels III and IV could be obtained.
      However, for this thickness range, even greater differences in survival could be
      obtained by merely comparing Breslow subgroups (i.e., < or = 0.8 mm vs. > 0.8-1.0
      mm, < or = 0.9 mm vs. > 0.9-1.0 mm). CONCLUSION: The authors' data suggested
      that, after controlling for Breslow depth, Clark level was not a good prognostic
      indicator for survival. If the AJCC's objective is to design a classification
      system that will reliably predict the higher risk melanomas, then the system
      should be based on tumor thickness, which is clearly a better prognostic
      indicator, and should not be modified because of Clark level.

PMID- 11251951
TI  - Dermoscopic criteria for melanoma in situ are similar to those for early invasive
      melanoma.
AB  - BACKGROUND: Dermoscopy is a noninvasive technique that increases the diagnostic
      accuracy of pigmented skin lesions, particularly improving the diagnosis of
      patients with cutaneous melanoma in situ (CMIS) and early invasive melanoma. To
      establish reliable and reproducible dermoscopic criteria for the diagnosis of
      CMIS, the authors conducted a retrospective clinical study of 37 patients with
      CMIS and 53 patients with invasive cutaneous melanomas (ICM). METHODS: The 37
      patients with CMIS were divided into three groups: those with CMIS lesions
      measuring < or = 5 mm in greatest dimension (8 patients), those with CMIS lesions
      measuring from > 5 mm to < or = 10 mm in greatest dimension (20 patients), and
      those with CMIS lesions measuring > 10 mm in greatest dimension (9 patients). The
      53 patients with ICM were divided into two groups according to Breslow index:
      those with ICM lesions measuring < or = 0.75 mm in tumor thickness (19 patients)
      and those with ICM lesions measuring > 0.75 mm in tumor thickness (34 patients).
      Lesions were examined with a dermatoscope and were photographed at a
      magnification of x10. Dermoscopic criteria were evaluated from examination of the
      photomicrographs. RESULTS: Blue-whitish veil, gray-blue areas, black dots, and
      irregular extensions and branched streaks were the most relevant dermoscopic
      criteria for CMIS and were present in 78%, 76%, 73%, and 62% of lesions,
      respectively. Brown globules, irregular pigment network, pseudopods, and
      depigmentation were present in 57%, 54%, 54%, and 51% of CMIS lesions,
      respectively. White scar-like areas and linear and/or dotted vascular patterns,
      two criteria that are associated frequently with ICM, were not found in our
      patients with CMIS. No clinically significant differences were observed between
      the three groups of CMIS patients. CONCLUSIONS: Dermoscopic criteria for CMIS
      were similar to those for ICM, although white scar-like areas and linear and/or
      dotted vascular patterns were observed only in patients with ICM. Dermoscopic
      criteria appeared to be independent of CMIS lesions size.

PMID- 11251952
TI  - Antitumoral effect of recombinant mistletoe lectin on chemically induced urinary
      bladder carcinogenesis in a rat model.
AB  - BACKGROUND: The objective of this study was to determine the effect of
      intravesically applied, recombinant, galactoside specific mistletoe lectin (rML)
      on chemically induced tumor development in the urinary bladder of rats. METHODS:
      For tumor induction, rats were treated with four biweekly 1.5 mg doses of N
      methyl-N-nitrosourea (NMU) intravesically (Weeks 0, 2, 4, and 6). The control
      group (n = 39 + 17 rats) received no other treatment. The four therapy groups
      also received rML twice weekly according to one of the following instillation
      regimens: 1) 30 ng rML per instillation from Week 8 to Week 13 (Group a: n = 14
      rats), 2) 150 ng rML per instillation from Week 8 to Week 13 (Group b: n = 23 +
      15 rats), 3) 30 ng rML per instillation from Week 14 to Week 19 (Group c: n = 22
      rats), and 4) 150 ng rML per instillation from Week 14 to Week 19 (Group d: n =
      19 rats). After the rats were asphyxiated at Week 21, the urinary bladders were
      excised in toto and examined histopathologically. To study the immunomodulatory
      effects of intravesically applied rML, 17 animals from the control group and 15
      animals from Group b were asphyxiated at Week 13, and urinary bladder tissue was
      analyzed by semiquantitative reverse transcriptase-polymerase chain reaction
      analysis for mRNA expression of interferon-gamma, interleukin-10, and Fas ligand.
      RESULTS: By Week 21, atypical hyperplasia and neoplastic transformation were
      found in 82% of the animals in the control group. In contrast, in all four
      cohorts that were treated with rML, significantly lower rates of atypical
      hyperplasia and neoplastic transformation were found (Group a, 50%; Group b, 52%;
      Group c, 45%; and Group d, 42%). By Week 13, in the bladder tissue of 15 rML
      treated animals from Group b, lower expression of interleukin-10 mRNA was
      measured, whereas the expression levels of interferon-gamma mRNA and Fas ligand
      mRNA were comparable to those of 17 animals from the control group. CONCLUSIONS:
      The current data provide evidence for an inhibitory effect of rML on experimental
      urothelial carcinogenesis that does not seem to be due to interferon-gamma and/or
      interleukin-10 dependent mechanisms.

PMID- 11251953
TI  - Low expression of p27(Kip1), a cyclin-dependent kinase inhibitor, is a marker of
      poor prognosis in synovial sarcoma.
AB  - BACKGROUND: Low expression of p27(kip1), a dominant cyclin-dependent kinase
      inhibitor involved in G1-S transition of the cell cycle, recently has been
      reported to be associated with aggressive tumor growth. It has been shown that
      active cell proliferation alludes to poor prognosis in patients with synovial
      sarcoma. However, to the authors' knowledge, little is known about the
      clinicopathologic significance of p27(kip1) in synovial sarcoma. METHODS:
      p27(kip1) expression was examined immunohistochemically in 55 cases of primary
      synovial sarcoma, and the relations between p27(kip1) expression and several cell
      proliferation markers, i.e., mitotic index (MI), Ki-67 labeling index (Ki-67 LI),
      and clinicopathologic parameters related to poor prognosis, were determined.
      Univariate and multivariate survival analyses were performed to evaluate the
      prognostic significance of p27(kip1) expression in synovial sarcomas. RESULTS:
      p27(kip1) labeling index (p27(kip1) LI) correlated inversely with MI (r = -0.44,
      P = 0.0007) and Ki-67 LI (r = -0.63, P < 0.0001). Of the clinicopathologic
      parameters examined, tumor necrosis (P = 0.019) and American Joint Committee on
      Cancer (AJCC) stage (P = 0.021) correlated significantly with p27(kip1) LI.
      Survival analysis showed that p27(kip1) LI was an independent prognostic factor
      for overall survival in patients with synovial sarcoma (P = 0.0031). CONCLUSIONS:
      The study results suggested that low expression of p27(kip1) may be useful as a
      marker of poor-prognosis synovial sarcoma.

PMID- 11251954
TI  - Localization of endostatin in rat and human gliomas.
AB  - BACKGROUND: Endostatin is a potent inhibitor of endothelial cell proliferation,
      angiogenesis, and tumor growth. Its occurrence and localization has not yet been
      examined in human brain tumors. The authors report the production of a monoclonal
      antibody and detection of endostatin in rat and human gliomas by
      immunohistochemistry. METHODS: The authors analyzed localization and tissue
      distribution of endostatin in 41 paraffin embedded glioma samples (18
      glioblastoma multiforme, 7 WHO Grade III astrocytomas, 13 fibrillary, and 3
      protoplasmic WHO Grade II astrocytomas) of human origin and 21 rat C6 gliomas by
      immunohistochemistry. Double labeling experiments confirmed the origin of
      endostatin-labeled cells. RESULTS: Endostatin immunoreactivity was detected in
      tumor cells, endothelial cells, macrophages, and lymphocytes of both rat and
      human gliomas. The percentage of cells labeled with the endostatin antibody was
      significantly lower (P = 0.0126) in the tumor parenchyma of human glioblastomas
      than in WHO Grade II astrocytomas. CONCLUSIONS: Endostatin was present in various
      cell types in rat and human gliomas in vivo. Lower levels in glioblastomas than
      in WHO Grade II astrocytomas might have reflected the shift of a probable
      regulatory balance between promoters and inhibitors of angiogenesis towards
      facilitation of neovascularization.

PMID- 11251956
TI  - The role of social and psychologic resources in caregiving of cancer patients.
AB  - BACKGROUND: The role of social support and personality within the cancer
      caregiving process has remained a relatively unexplored area. The current
      longitudinal study examines the main and moderating effects on caregiver
      experiences and caregiver's depression over time of various social and
      psychologic resources. METHODS: Newly diagnosed colorectal carcinoma patients and
      their partners (N = 148) were included and data were obtained at three
      measurement points: 2 weeks prior to hospital admission and 3 months and 6 months
      after discharge. The initial and change scores of the caregiver's negative and
      positive social interactions and personality attributes (mastery, neuroticism,
      and extraversion) were included to assess their impact on caregiver experiences
      and depression over time. RESULTS: The main effects of social and psychologic
      resources on caregiver experiences were found to be small to absent. With respect
      to caregiver depression, both initial scores and changes in neuroticism, mastery,
      and negative social interactions were shown to have substantial main effects over
      time. Moreover, daily emotional support and mastery modified the relations
      between caregiver experiences and caregiver depression. Caregivers with a low
      level of daily emotional support, as well as those with a low score on mastery
      and who also perceived caregiving in a more negative way were identified as more
      depressed over time. CONCLUSIONS: The results of the current study demonstrate
      the importance of including various social and psychologic resources in studying
      the cancer caregiving process. It illustrates the distinctive impact of these
      resources on the depression of caregivers of patients with cancer, and therefore
      helps healthcare providers understand why some persons adapt better than others
      to their caregiving role.

PMID- 11251955
TI  - Comparison of 5-fluorouracil alone, 5-fluorouracil with levamisole, and 5
      fluorouracil with hepatic irradiation in the treatment of patients with residual,
      nonmeasurable, intra-abdominal metastasis after undergoing resection for
      colorectal carcinoma.
AB  - BACKGROUND: The authors conducted a randomized Phase III trial of three treatment
      regimens for patients with residual, nonmeasurable, intra-abdominal metastatic
      disease after undergoing resection for primary colorectal carcinoma. METHODS: To
      be eligible for this study, patients had to be both free of other malignancies
      and capable of starting their therapy within 3-6 weeks after surgery. They were
      required to have an Eastern Cooperative Oncology Group performance status < 3; to
      be chemotherapy, radiation, and immunotherapy naive; to have adequate bone
      marrow, renal, and hepatic function; and to provide written, informed consent.
      The patients were divided into two cohorts: patients with no demonstrable hepatic
      metastasis (Group A) and patients with hepatic metastasis (Group B). RESULTS: The
      229 patients in Group A were randomized to receive either 5-fluorouracil (5-FU)
      (n = 116 patients) or 5-FU with levamisole (n = 113 patients). The median
      survival (15.4 months and 15.3 months, respectively, for Groups A and B) was
      virtually identical. The two groups also were similar in terms of time to
      treatment progression, which was 7.9 months for group that received 5-FU alone
      7.7 months for the group that received levamisole with 5-FU. The 168 patients in
      Group B with hepatic metastasis underwent a three-way randomization: 5-FU alone
      (n = 60 patients), 5-FU with levamisole (n = 54 patients), and 5-FU with hepatic
      irradiation (n = 54 patients). The median overall survival for the three
      treatment arms were similar, with 17.3 months for the group that received 5-FU
      alone, 16 months for the group that received 5-FU with levamisole, and 14.4
      months for the group that received hepatic irradiation in addition to 5-FU: The
      time to treatment failure was 6.7 months, 6.8 months, and 8.3 months,
      respectively, for the three groups. The toxicity experienced by patients was as
      expected with the regimens, and no differences were observed between any of the
      treatment groups. The primary toxicities were hematologic and gastrointestinal.
      There was one treatment-related death due to adult respiratory distress syndrome,
      which occurred on the first day of the fourth cycle of 5-FU and levamisole. Other
      Grade 4 toxicities included nine patients with Grade 4 leukopenia, one patient
      with Grade 4 sepsis, and one patient with Grade 4 gastrointestinal toxicity,
      including blood loss and diarrhea. CONCLUSIONS: This study showed no treatment
      advantage for any of the combined modalities over 5-FU alone in this group of
      patients with intra-abdominal, nonmeasurable disease.

PMID- 11251957
TI  - Use of vitamins, minerals, and nutritional supplements by participants in a
      chemoprevention trial.
AB  - BACKGROUND: The growing use of vitamins, minerals, and nutritional supplements
      has the potential to influence the design and interpretation of randomized
      controlled trials of chemopreventive agents. To the extent that these
      complementary agents are effective, they could limit the ability of trials to
      demonstrate an effect of the agents under study. METHODS: During the course of a
      colorectal neoplasia chemoprevention trial using aspirin in a group of colorectal
      carcinoma survivors, the authors obtained information on the use of vitamins,
      minerals, and supplements at baseline and every 6 months. The information from
      622 study participants was categorized and enumerated. RESULTS: One or more
      supplements were used at some time by 341 (55%) subjects. Among those who took
      supplements, 66% took more than 1 and 13% took 5 or more. The mean number of
      supplements taken was 2.6 (1.7 standard deviation). Vitamins were the most
      commonly used (49%), followed by minerals (22%), botanicals (13%), and others
      (5%). Among the vitamins, the most frequently used were multivitamins (38% of
      subjects), vitamin C (18%), and vitamin E (22%). Calcium (16%) was the most
      frequent mineral. Among users, there were no differences in supplement use by age
      or gender. CONCLUSIONS: Supplement use was common among colorectal carcinoma
      survivors enrolled in a prevention trial. Investigators should record the
      information on supplement use so that the possible impact of the supplements on
      trial endpoints can be evaluated. It may be necessary to increase the size of
      studies if many of the subjects take potentially effective supplements.

PMID- 11251958
TI  - Hepatocellular carcinoma incidence in Florida. Ethnic and racial distribution.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC), the primary form of liver carcinoma,
      is increasing in incidence worldwide. The increasing numbers of Hispanic
      immigrants in Florida suggest that the rate of HCC in the Hispanic population
      should be of special concern. This study describes racial and ethnic distribution
      and trends of incident HCC in Florida from 1985 to 1995. METHODS: A total of 2837
      cases of incident HCC from 1985 to 1995 were examined from Florida's incident
      cancer registry, the Florida Cancer Data System. Age standardized and age
      specific average annual incidence rates were calculated for the state of Florida
      by gender and by racial and ethnic group. RESULTS: Over the study period, the
      average annual incidence HCC rates in Florida among male and female Hispanics and
      blacks were consistently and significantly twice the rate of white males and
      females as standardized rate ratios. Males were at least twice as likely to have
      HCC compared with females in all three racial and ethnic subpopulations.
      CONCLUSIONS: The incidence of HCC in Florida was comparable to the overall U.S.
      incidence with respect to average annual incidence and gender distribution.
      Florida blacks and Hispanics are at significantly increased risk for HCC
      incidence compared with Florida whites. These results have implications for
      preventive HCC recommendations in growing racial and ethnic subpopulations in the
      United States.

PMID- 11251959
TI  - Primary peritoneal malignant mixed Mullerian tumors. A clinicopathologic,
      immunohistochemical, and genetic study.
AB  - BACKGROUND: Primary peritoneal malignant mixed Mullerian tumors (MMMTs) are
      rarely reported in the literature. METHODS: The clinical, pathologic, and
      immunohistochemical features of five cases of MMMT of female peritoneum were
      analyzed. The tumors were also investigated for expression of hormone receptors,
      specific BRCA-1 mutations, and clonality. RESULTS: The patients' ages ranged from
      33 to 67 years. They presented with abdominal pain or mass. One case of
      peritoneal MMMT was associated with a synchronous endometrial carcinoma whereas
      another case was detected 2 years after the diagnosis of a primary adenocarcinoma
      of the fallopian tube. One patient died 1 month after diagnosis whereas 2
      patients died with disease within 1 year. Both carcinomatous and sarcomatous
      elements are present in all the tumors. Squamous differentiation was noted in two
      cases. Heterologous elements, including chondroid, rhabodomyoblastic, and osteoid
      differentiation were detected in all tumors. Immunohistochemical studies confirm
      the biphasic differentiation with variable demonstration of neural and smooth
      muscle differentiation. All five MMMTs were negative for estrogen and progestogen
      receptors although the related endometrial and tubal carcinomas were positive.
      Heteroduplex analysis used to screen for specific BRCA-1 mutations were negative
      in all five MMMTs. Clonality study of the two MMMTs found in association with
      endometrial carcinoma and tubal carcinoma was inconclusive. CONCLUSIONS: Our
      study confirmed that primary peritoneal MMMTs were aggressive tumors with poor
      prognosis. The presence of synchronous or metachronous genital carcinomas
      suggests multifocal tumorigenesis from tissue of same embryologic origin. The
      lack of hormone receptor in these tumors indicates deviation from hormonal
      control. Specific BRCA-1 mutations found in ovarian carcinoma in Chinese patients
      could not be detected in our series.

PMID- 11251960
TI  - Increased cancer risk in the offspring of women with colorectal carcinoma. A
      Swedish Register-Based Cohort Study.

PMID- 11251961
TI  - The correlation of serial prostate specific antigen measurements with clinical
      outcome after external beam radiation therapy of patients for prostate carcinoma.

PMID- 11251964
TI  - Induction of human tumor-loaded dendritic cells.
AB  - A preferred anti-cancer vaccine would be tumor-specific, simple to rapidly
      construct and safe to administer. It would permit immunization against a spectrum
      of the tumor's distinctive antigens, without requiring their prior
      identification. Toward these goals, we describe a modification of standard
      extracorporeal photopheresis (ECP) which initiates, within a single day, both
      monocyte-to-dendritic cell (DC) differentiation and malignant cell apoptosis. The
      transition of monocytes to immature DCs was identified by the expression of
      cytoplasmic CD83 and membrane CD36 in the absence of membrane CD14 staining, as
      well as induction of membrane CD83 expression. Differentiating DCs were avidly
      phagocytic and engulfed apoptotic malignant T cells. Differentiating DCs were
      capable of stimulating significant proliferation of normal alloreactive
      lymphocyte responders, indicting increased expression of membrane MHC class II
      molecules. This approach provides a clinically practical means of developing
      tumor-loaded cells that have initiated the transition to DCs without the
      requirement of exogenous cytokines, excessive cellular manipulation or isolation.
      Construction of DC vaccines using this methodology can be generalized to other
      diseases and may offer a novel approach for improved cancer immunotherapy.

PMID- 11251963
TI  - Isolation of a novel human lung-specific gene, LUNX, a potential molecular marker
      for detection of micrometastasis in non-small-cell lung cancer.
AB  - We have isolated a novel human lung-specific gene, LUNX (lung-specific X
      protein), by differential-display mRNA analysis. The full-length cDNA contained
      1,015 nucleotides including an open reading frame of 768 nucleotides encoding 256
      amino acids. We localized the gene to chromosomal region 20p11.1-q12 by radiation
      hybrid mapping. Using an RT-PCR assay specific for LUNX mRNA, 35 non-small-cell
      lung-cancer (NSCLC) tumors and 0 of 16 normal lymph nodes were positive.
      Furthermore, LUNX mRNA expression was enhanced in 26 (84%) of 31 NSCLC tumors vs.
      corresponding cancer-free lung tissues by semi-quantitative analyses with
      multiplex RT-PCR. We assessed the possibility of LUNX mRNA as a molecular marker
      for detection of micrometastasis in dissected lymph nodes obtained from 20
      patients with NSCLC tumors. LUNX mRNA was detected in 16 (80%) of 20
      histologically positive lymph nodes and 21 (25%) of 84 histologically negative
      lymph nodes. Comparative analyses of the conventional histological examination
      and the RT-PCR detection assay for LUNX mRNA showed that the detection rate of
      metastases in lymph nodes by the RT-PCR assay was higher in 12 and consistent in
      6 of the total 20 NSCLC patients. We demonstrate that the LUNX RT-PCR assay is a
      potential diagnostic method for detection of micrometastases in lymph nodes of
      NSCLC patients.

PMID- 11251965
TI  - Over-expression of heat shock proteins in carcinogenic endometrium.
AB  - We have previously shown that the subcellular localization of beta-catenin
      changes according to the cell proliferation status of the human endometrium,
      suggesting a role of intercellular transduction in cell growth control in human
      endometrium not only in the physiological but also in the carcinogenic condition.
      To further study the possible role of heat shock proteins (HSPs) in growth
      control, we immunohistochemically analyzed 92 endometrial samples, 30 of normal
      endometrium, 20 of endometrial hyperplasia and 42 of endometrial cancer, for
      expression of HSP27, HSP70, HSP90, estrogen receptor (ER) and progesterone
      receptor. HSP27 and HSP90 were detected in endometrial epithelium strongly in the
      proliferative phase and weakly in the secretory phase during the menstrual cycle
      according to the serum estradiol level. However, they were over-expressed in
      endometrial hyperplasia, especially HSP27. In endometrial cancer, HSP27
      expression was heterogenic among the glands and lower than that in the
      proliferative phase and endometrial hyperplasia. HSP27 over-expression was also
      observed in samples including endometrial cancer and associated hyperplasia.
      Results of Western blotting followed those of immunohistochemistry. HSP70 was not
      changed during the menstrual cycle, as HSP27 and HSP90 were, and was rather
      stably expressed in endometrial hyperplasia and cancer. Our results suggest that
      HSP27 and HSP90 contribute to cell proliferation in endometrial epithelium and
      that over-expression of HSP27 in endometrial hyperplasia occurs as a result of
      the activated condition of ER, though in cancer it decreases according to the
      loss of function of ER.

PMID- 11251966
TI  - Endoplasmic reticulum/cytosolic localization of von Hippel-Lindau gene products
      is mediated by a 64-amino acid region.
AB  - Inactivation of the von Hippel-Lindau (VHL) tumor-suppressor gene causes both the
      familial cancer syndrome VHL disease and corresponding sporadic tumor types,
      including renal-cell carcinoma. Subcellular localization of VHL gene products was
      determined by indirect immunofluorescence. Both native and exogenously expressed
      VHL proteins displayed a cytoplasmic peri-nuclear immunostaining pattern, which
      co-localized with markers for the endoplasmic reticulum (ER). In addition,
      subcellular fractionation indicated that both native and exogenously expressed
      VHL products are found predominantly in the cytosolic compartment. Deletion
      analyses demonstrated that a 64-amino acid region of VHL (residues 114-177) is
      responsible for cytosolic as well as ER subcellular localization. Taken together,
      the immunostaining and biochemical fractionation studies suggest that VHL
      localizes to the cytosolic face of the ER. The relationship between VHL
      subcellular localization and VHL-associated ubiquitination was examined. Chimeric
      VHL-green fluorescent protein (GFP) products, which localized to the peri-nuclear
      region, were shown to undergo ubiquitination. VHL amino acids 114-177 were
      necessary and sufficient for this modification. Consistent with a role of VHL in
      ubiquitination, expression of VHL led to enhanced ubiquitination of cellular
      proteins, and amino acids 114-177 were also critical for this effect. Therefore,
      amino acids 114-177 were required for accurate VHL subcellular localization,
      ubiquitination of VHL-GFP products and VHL-dependent increases in cellular
      ubiquitination. Since mutations in this region of VHL are frequently detected in
      renal-cell carcinomas, these results suggest that proper VHL subcellular
      localization and associated ubiquitination functions may be necessary for VHL
      mediated tumor suppression.

PMID- 11251967
TI  - The role of caspase 3 in producing cytokeratin 19 fragment (CYFRA21-1) in human
      lung cancer cell lines.
AB  - The CYFRA 21-1 assay, which detects cytokeratin 19 (CK19) fragment, is widely
      used as a tumor marker for lung cancer, particularly non-small cell lung cancer.
      However, the reason that some lung cancer cell lines release CYFRA 21-1 in
      culture supernatants and others do not remains unclear. We hypothesized that the
      release of CYFRA 21-1 might be related to the expression of CK19 and caspase 3.
      In order to prove this, the quantities of mRNA for CK19 were evaluated by the
      competitive reverse transcriptase-polymerase chain reaction (RT-PCR). CK19
      protein synthesis was also evaluated by Western blotting and
      immunohistochemistry, and the levels of CYFRA 21-1 in the culture supernatant
      were measured by an immunoradiometric assay. The expression of mRNA for caspase 3
      was evaluated by the RT-PCR, and caspase 3 protein synthesis was also evaluated
      by immunohistochemistry. In 13 lung cancer cell lines, the amounts of mRNA for
      CK19 correlated with the levels of CYFRA 21-1 in culture supernatants, results of
      Western blotting for CK19, and positivities of immunohistochemistry for CK19. In
      5 cell lines that produced a significant amount of CYFRA 21-1, the level of CYFRA
      21-1 correlated with the positivity of RT-PCR for caspase 3 and
      immunohistochmistry for caspase 3. This suggests that caspase 3 played a role in
      the formation of CYFRA 21-1. In addition, the specific inhibitor of caspase 3
      significantly inhibited the release of CYFRA 21-1 in culture supernatants. In
      conclusion, we demonstrate that caspase 3, which cleaves several intermediate
      filaments and carries out cell apoptosis, played an important role in producing
      CYFRA 21-1 in human lung cancer cell lines.

PMID- 11251968
TI  - CDNA microarray gene expression analysis of B-cell chronic lymphocytic leukemia
      proposes potential new prognostic markers involved in lymphocyte trafficking.
AB  - Human cancer is characterized by complex molecular perturbations leading to
      variable clinical behavior, often even in single-disease entities. We performed a
      feasibility study systematically comparing large-scale gene expression profiles
      with clinical features in human B-cell chronic lymphocytic leukemia (B-CLL). cDNA
      microarrays were employed to determine the expression levels of 1,024 selected
      genes in 54 peripheral blood lymphocyte samples obtained from patients with B
      CLL. Statistical analyses were applied to correlate the expression profiles with
      a number of clinical parameters including patient survival and disease staging.
      We were able to identify genes whose expression levels significantly correlated
      with patient survival and/or with clinical staging. Most of these genes code
      either for cell adhesion molecules (L-selectin, integrin-beta2) or for factors
      inducing cell adhesion molecules (IL-1beta, IL-8, EGR1), suggesting that
      prognosis of this disease may be related to a defect in lymphocyte trafficking.
      This report demonstrates the feasibility of a systematic integration of large
      scale gene expression profiles with clinical data as a general approach for
      dissecting human diseases.

PMID- 11251969
TI  - Association between CagA+ Helicobacter pylori infection and p53, bax and
      transforming growth factor-beta-RII gene mutations in gastric cancer patients.
AB  - We assessed the possible association between CagA+ Helicobacter pylori infection
      and gastric carcinogenesis in gastric cancer patients. Gastric biopsy specimens
      were obtained from 64 patients with gastric cancer and were histologically
      classified into intestinal and diffuse types. H. pylori infection was determined
      by cultivation, flaA-PCR and serum antibody against CagA. p53, BAX and
      transforming growth factor-beta-RII (TGFbeta-RII) gene mutations were analyzed by
      PCR-SSCP and direct sequencing. Intestinal and diffuse types of cancer were
      detected in 45 and 19 patients, respectively. H. pylori infection was found in 55
      (85.9%) of 64 patients. There was no significant difference in H. pylori
      positivity between intestinal and diffuse types. However, the CagA antibody was
      positive in 15 (78.9%) of 19 patients with the diffuse type and in 22 (48.9%) of
      45 patients with the intestinal type (p = 0.030). Among the 55 H. pylori-positive
      cases, 11 (29.7%) of the 37 patients in the CagA+ group were found to have p53
      alterations, compared with 2 (11.1%) in the 18 CagA- group (p = 0.182). Moreover,
      among the 64 gastric cancer patients, p53 alterations were more frequently found
      in the CagA+ group (29.7%) than in the H. pylori-positive CagA- and H. pylori
      negative groups (7.4%; p = 0.033). BAX gene mutations were found in 19 (29.7%) of
      64 patients and there was no relationship among CagA seropositivity, cancer
      stages and histopathological phenotypes. In contrast, the TGFbeta-RII gene
      mutation was only detected in one CagA- patient. The results suggest that CagA+
      H. pylori infection may have an important role in the development of gastric
      cancer patients with p53 mutations

PMID- 11251970
TI  - A population based cohort study of patients with multiple colon and endometrial
      cancer: correlation of microsatellite instability (MSI) status, age at diagnosis
      and cancer risk.
AB  - Hereditary non-polyposis colorectal cancer, HNPCC, is an autosomal dominant
      condition predisposing to cancers of primarily the colorectum and the
      endometrium. The aim of our study was to identify persons at a high risk of
      hereditary colorectal cancer and to estimate their risk of colon and other HNPCC
      associated tumours. Family histories of cancer were obtained on 89 persons with
      double primary (DP) cancers of the colon and the endometrium. The cancer risks in
      their 649 first-degree-relatives (FDR) were analysed. The microsatellite
      instability (MSI) status of the tumour of the proband was also analysed and the
      cancer risks were estimated in relation to MSI status and age at diagnosis in the
      proband (over or under 50 years). The overall standardised incidence ratio (SIR)
      was 1.69 (95% CI; 1.39-2.03). In the =50-year-old cohort the SIR was 2.67 (95%
      CI; 2.08-3.38). Colon, rectal and uterus cancer exhibited significantly increased
      risks. This risk was further increased in the =50-year-old MSI positive families.
      Several =50-year-old MSI negative HNPCC-like families with increased risks were
      also identified. In conclusion a FDR to a person with a DP cancer of the
      colorectum or the colon/endometrium have a significantly increased risk of having
      a colorectal or other HNPCC-associated cancers if the proband is diagnosed with
      one of the cancers before age 50. These families are candidates for genetic
      counselling and colorectal screening programmes. Mutations in mismatch repair
      genes can explain some of the increased risk in these families, but mutations in
      MSI negative families are probably due to other colon cancer susceptibility genes
      not yet described.

PMID- 11251971
TI  - Gene expression profiling of malignant mesothelioma cell lines: cDNA array study.
AB  - To reveal genes relevant for malignant mesothelioma (MM), we carried out cDNA
      array experiments on 4 MM cell lines and 2 primary mesothelial cell cultures
      established from pleural fluid of non-cancer patients. Human cancer gene filters
      including 588 genes were used for the cDNA array experiments. Our study revealed
      26 over-expressed genes that play a role in the regulation of cell fate, cell
      cycle, cell growth and DNA damage repair and 13 under-expressed genes encoding
      growth factors, receptors and proteins involved in cell adhesion, motility and
      invasion to be common to 3 or 4 MM cell lines. We confirmed the cDNA array
      results using RT-PCR for 5 of the over-expressed genes and for 3 of the under
      expressed genes. Our study presents gene expression profiles in MM cell lines and
      shows the involvement of several genes, such as those encoding JAGGED1, ser/thr
      protein kinase NIK, Ku80 and cyclin D2, novel in MM.

PMID- 11251972
TI  - Sex-specific mortality from adult T-cell leukemia among carriers of human T
      lymphotropic virus type I.
AB  - Perinatal infection with human T-lymphotropic virus type I (HTLV-I) is considered
      a risk factor for adult T-cell leukemia (ATL). Incidence of ATL in Japan is
      generally higher in males compared with females, perhaps partly due to an earlier
      average age of infection among males. We estimated sex-specific ATL mortality
      among perinatally-infected HTLV-I carriers in the prospective Miyazaki Cohort
      Study in Japan. Based on the approximated proportion of perinatally-infected
      carriers, the relative risk (RR) of ATL for males compared with females was
      calculated. Six ATL deaths (4 males, 2 females) occurred among the 550 HTLV-I
      carriers in the cohort during 13 years of follow-up. The overall ATL mortality
      was 190.5 (95% CI 51.9-487.7) per 10(5) person-years for males and 51.7 (6.3
      186.8) per 10(5) person-years for females (age-standardized RR = 3.9, p=0.02). By
      approximating the number of persons who acquired infection perinatally, the
      estimated mortality among those perinatally-infected HTLV-I carriers was 209.1
      (57.0-535.2) per 10(5) person-years for males and 60.9 (7.4-219.9) per 10(5)
      person-years for females (age-standardized RR = 3.7, p=0.02). The adjusted RR
      changed minimally from the unadjusted RR, suggesting that earlier age of
      infection alone is unlikely the explanation for the male predominance in ATL.
      Based on the small number of cases available for analysis, aspects of gender
      itself appear to play a role in the development of this malignancy.

PMID- 11251973
TI  - Unbalanced expression of HLA-A and -B antigens: a specific feature of cutaneous
      melanoma and other non-hemopoietic malignancies reverted by IFN-gamma.
AB  - Conflicting evidences suggested that levels of HLA-A and -B antigens expressed on
      normal and neoplastic cells of given individuals are genetically predetermined,
      or, on the other hand, regulated by molecular mechanisms generating the down
      regulated expression of HLA-B antigens frequently observed on melanoma cells. In
      our study, we quantitated, both at the protein and mRNA level, the amounts of HLA
      A and -B antigens constitutively expressed on 23 primary cultures of metastatic
      melanomas and on autologous peripheral blood mononuclear cells (PBMC). Flow
      cytometric analyses identified a significantly (p < 0.01) lower expression of HLA
      B antigens on melanoma cell cultures but not on autologous PBMC. Consistently,
      lower amounts of HLA-B antigens mRNA were detected by RNase protection assay
      exclusively in neoplastic cells. This unbalanced expression of HLA-A and -B
      antigens was readily reverted by interferon (IFN)-gamma but not by the DNA
      hypomethylating agent 5-aza-2'-deoxycytidine in 4 melanoma cell cultures
      investigated. Significantly (p < 0.05) lower levels of HLA-B antigens were also
      detected on cells from solid malignancies of different histotypes but not on
      neoplastic cells from hemopoietic neoplasms; levels of HLA-B antigens were
      rapidly up-regulated by IFN-gamma exclusively on non-hemopoietic transformed
      cells. Together, these data strongly argue against a genetic predetermination of
      the amounts of HLA-A and -B antigens expressed on normal and neoplastic cells of
      distinct melanoma patients and suggest that constitutively low levels of HLA-B
      antigens are a specific feature of non-hemopoietic transformed cells that is
      controlled by common regulatory mechanism(s) and that is possibly shared by non
      hemopoietic normal cells.

PMID- 11251974
TI  - Locoregional treatment of low-grade B-cell lymphoma with CD3xCD19 bispecific
      antibodies and CD28 costimulation. I. Clinical phase I evaluation.
AB  - We describe the first clinical application of T-cell-recruiting bispecific
      antibodies directly into the tumor without the need to preactivate the effector
      cells. In a Phase I clinical trial, 10 patients with low-grade B-cell lymphoma
      were treated by a single locoregional injection of CD3xCD19 bispecific
      antibodies. Costimulatory signaling, which is required for the optimal activation
      of resting T cells, was provided by the simultaneous administration of CD28
      antibodies. Equal amounts of both antibodies were injected together at 4
      different dose levels (30 microg: 3 patients; 270 microg: 3 patients; 810 microg:
      3 patients; 1,600 microg: 1 patient). The injection was well tolerated with mild
      to moderate adverse effects (2/10 patients) consisting of erythema and fever at
      the third dose level. The maximum tolerated dose was not reached at 810 microg of
      injected antibodies. Three patients showed a serum peak of TNFalpha on day 2 or 3
      after the antibody application, reflecting rather an activation of CD4-positive T
      cells than an FcR-mediated effect. Five patients developed anti-mouse antibodies
      after injection of the murine immunoglobulins. Nine patients were evaluable for
      restaging examinations 6 weeks after the antibody application, with 2 of them
      (22%) showing a local clinical response. We found that a single locoregional
      injection of CD3xCD19+CD28 antibodies is feasible up to a dose of at least 1,600
      microg of each antibody. However, the development of human anti-mouse antibodies
      points toward the requirement for new formats of bispecific proteins with reduced
      immunogenicity.

PMID- 11251975
TI  - Locoregional treatment of low-grade B-cell lymphoma with CD3xCD19 bispecific
      antibodies and CD28 costimulation. II. Assessment of cellular immune responses.
AB  - Ten patients with advanced B-cell lymphoma were treated with a single
      locoregional injection of CD3xCD19 bispecific and costimulating CD28 monospecific
      antibodies to activate tumor-infiltrating T-lymphocytes. Antibodies were
      administered at 4 different dose levels (30 microg, 270 microg, 810 microg, 1,600
      microg of each antibody) either by intratumoral or intralymphatic injection. Most
      patients developed responses within different compartments of the immune systems
      (T cells, NK cells) subsequent to the antibody application. Comparative studies
      in 2 patients of which treated as well as untreated lymph nodes were available
      revealed the up-regulation of T-cell activation markers induced by the antibody
      injection. Additionally, in 1 patient the induction of apoptosis of lymphoma B
      cells in the antibody-treated lymph node was observed. Specificity analyses of
      peripheral blood T cells by means of IFN-gamma ELISpot measurement indicated the
      recruitment of idiotype-specific T cells, as in 1 out of 3 investigated patients
      an increased T-cell response toward autologous idiotype peptides could be
      demonstrated. We conclude that a single injection of CD3xCD19 bispecific
      antibodies is capable to induce an activation of autologous T lymphocytes if
      simultaneous costimulatory signaling by CD28 antibodies is provided. Furthermore,
      our data suggest that at least in some patients lymphoma-specific T cells can be
      recruited by this immunotherapeutic approach toward B-cell lymphoma.

PMID- 11251977
TI  - Role of Fas ligand expression in promoting escape from immune rejection in a
      spontaneous tumor model.
AB  - Tumors escape immune-mediated rejection by a variety of mechanisms during tumor
      progression. The elucidation of these mechanisms in vivo suffers from a lack of
      suitable models of spontaneous tumor formation escaping active specific
      immunotherapy (ASI). In a rat neu transgenic (rNeu-TG) mouse model of spontaneous
      breast tumor formation, we showed that rNeu-TG mice developed late escape tumors
      despite the presence of a persistent rNeu-specific immune response after ASI.
      Cell suspensions derived from these escape tumors grew in vaccinated tumor-free
      mice, whereas injected spontaneous tumor cells were rejected. Escape tumors
      retained rNeu or MHC class I expression but significantly upregulated Fas (CD95,
      Apo-1) ligand. We further demonstrated that Fas-L on escape tumor cells
      correlated with apoptosis of infiltrating T lymphocytes. Thus, our results
      provide evidence that spontaneous breast tumors upregulate Fas-L expression after
      vaccination that may promote tumor escape in vivo after ASI.

PMID- 11251976
TI  - Inhibition of tumor metastasis by adoptive transfer of IL-12-activated Valpha14
      NKT cells.
AB  - A unique lymphocyte lineage, the Valpha14 NKT cells, expresses both NK1.1 and an
      invariant antigen receptor encoded by Valpha14 and Jalpha281 gene segments.
      Valpha14 NKT cells play crucial roles in various immune responses, including
      autoimmune diseases, allergic reactions and anti-tumor immunity. Valpha14 NKT
      cells were demonstrated to be essential for anti-tumor effect of IL-12 in vivo.
      Here, we report that adoptive transfer of IL-12-activated Valpha14 NKT cells
      prevents hepatic metastasis of B16 melanoma. The injection of large amounts of IL
      2, IL-4, and IFN-gamma, which are cytokines produced by activated Valpha14 NKT
      cells, exhibited no significant inhibition of the metastasis of this melanoma.
      The cells prepared from the liver of IL-12-injected mice expressed a potent
      cytotoxic activity on B16 melanoma cells in vitro. Although the adoptive transfer
      of IL-12-activated Valpha14 NKT cells prevents hepatic metastasis of B16
      melanoma, activated NK cells from IL-12-injected RAG-1-/- mice failed to inhibit
      the metastasis of this melanoma. Thus, the anti-tumor effect of IL-12 can be
      replaced by adoptive transfer of IL-12-activated Valpha14 NKT cells but not by IL
      12-activated NK cells, suggesting a minor role of NK cells for the IL-12-mediated
      anti-tumor effect in this experimental system. Moreover, our studies have
      suggested the involvement of direct cytotoxic mechanisms rather than cytokine
      mediated immune responses at the effector phase of the Valpha14 NKT cell-mediated
      anti-tumor activity.

PMID- 11251978
TI  - Stimulation of intercellular communication of poor-communicating cells by gap
      junction-competent cells enhances the HSV-TK/GCV bystander effect in vitro.
AB  - We have previously shown that gap-junctional intercellular communication (GJIC)
      appears to play a role in the bystander effect that is observed in anticancer
      suicide gene therapy mediated by herpes simplex virus (HSV) thymidine kinase (tk)
      and ganciclovir (GCV). We now report that when connexin-expressing (Cx+) cells
      are present within a noncommunicating population of cells (Cx-), there is GJIC
      between the Cx+ and Cx- cells and that due to this stimulation of GJIC, the
      bystander effect also occurs when the 2 cell types are mixed. We transfected HeLa
      cells, which do not express any detectable level of connexin, with Cx43. The Cx+
      and Cx- HeLa cells were further transfected with the tk gene, giving 4
      phenotypes: Cx+tk-, Cx+tk+, Cx-tk+ and Cx-tk-. We observed GJIC between Cx+ and
      Cx- cells, but not between Cx- and Cx- cells, regardless of the tk genotype.
      Similarly, we observed the HSV-tk/GCV bystander effect in Cx+tk-/Cx-tk+ and
      Cx+tk+/Cx-tk- cocultures. The extent of the bystander effect in cocultures of
      Cx+tk- and Cx-tk+ cells was stronger than in cocultures of Cx+tk+ and Cx-tk-
      cells when each mixture had the same ratio of Cx+ and tk+ cells. These results
      suggest that Cx-expressing HeLa cells stimulate GJIC capacity between them and
      non-Cx-expressing HeLa cells, which mediates the bystander effect in mixtures of
      Cx+ cells and Cx- cells in vitro. Thus, Cx expression even in only a limited
      fraction of tumor cells may enhance the efficacy of the HSV-tk/GCV strategy by
      inducing a bystander effect.

PMID- 11251979
TI  - Lectin-deficient TNF mutants display comparable anti-tumour but reduced pro
      metastatic potential as compared to the wild-type molecule.
AB  - In this study, we characterised the anti-tumour as well as the pro-metastatic
      activities of TNF mutants deficient in their lectin-like activity.1619 We report
      that, despite reduced systemic toxicity as compared to wild-type (wt) mTNF, a
      (T104A) and a (T104A-E106A-E109A) mTNF mutant (triple mTNF) retained most of
      their necrotic and tumouristatic activities, as measured in a CFS-1 fibrosarcoma
      and a B16BL6 melanoma tumour model, respectively. These mutants also conserved
      their anti-angiogenic activity, as measured in an in vitro endothelial
      morphogenesis assay.26 In contrast, the pro-metastatic activity of the T104A and
      the triple mTNF mutants in the CFS-1 fibrosarcoma and the 3LL-R Lewis lung
      carcinoma tumour model was significantly lower than that of the wt molecule.
      These results thus indicate that the lectin-like domain of TNF is not implicated
      in its necrotic, tumouristatic and anti-angiogenic activities, but that it can
      contribute to the pro-metastatic effect of the cytokine. In conclusion, in view
      of their reduced systemic toxicity and pro-metastatic capacity, but their
      retained anti-tumour activities, lectin-deficient TNF mutants might prove to be
      therapeutically interesting alternatives to wt TNF.

PMID- 11251980
TI  - Pronounced antitumor efficacy of doxorubicin when given as the prodrug DOX-GA3 in
      combination with a monoclonal antibody beta-glucuronidase conjugate.
AB  - A glucuronide doxorubicin prodrug N-[4-doxorubicin-N-carbonyl (oxymethyl) phenyl]
      O-beta-glucuronyl carbamate (DOX-GA3) has been developed to improve the antitumor
      effects of doxorubicin (DOX). The prodrug was originally designed to be activated
      into drug by human beta-glucuronidase (GUS) released from tumor cells in necrotic
      areas of tumor lesions. The aim of this study was to further improve the
      antitumor effects of DOX-GA3 by means of antibody-directed enzyme prodrug therapy
      (ADEPT). We thus investigated if the administration of an enzyme-immunoconjugate
      prepared from the pancarcinoma Ep-CAM specific monoclonal antibody (MAb) 323/A3
      and beta-glucuronidase would result in improved antitumor effects because of
      additional enzyme localization in tumor tissue. In vitro, the prodrug DOX-GA3 was
      found to be 12-times less toxic than the parent drug DOX in a human ovarian
      cancer cell line. Immunospecific and complete activation of the prodrug took
      place when the cells were pretreated with 323/A3-beta-glucuronidase conjugate. In
      nude mice bearing s.c. human ovarian cancer xenografts (FMa) the maximum
      tolerated dose (MTD) of DOX-GA3 (500 mg/kg weekly x 2) was much higher when
      compared with that of DOX (8 mg/kg weekly x 2). In mice bearing well-established
      FMa xenografts, the standard treatment of DOX at the MTD (8 mg/kg weekly x 2)
      resulted in a tumor growth inhibition of 67%. Treatment with DOX-GA3 at a single
      dose of 500 mg/kg resulted in a better tumor growth inhibition of 87%. The
      combination of DOX-GA3 (500 mg/kg) with 323/A3-mGUS conjugate and anti-GUS MAb
      105, to clear circulating conjugate, improved the antitumor effect even further
      to 98%. At the lower dose of 250 mg/kg DOX-GA3 tumor growth inhibition (34%) was
      not better than that of DOX. The combination, however, of DOX-GA3 at 250 mg/kg
      and 323/A3-mGUS conjugate plus MAb 105 again greatly improved the antitumor
      effect (growth inhibition of 93%). DOX given at 8 mg/kg weekly x 2 did not result
      in tumor regressions. As a result of ADEPT, the number of regressions of tumors
      improved from 0 out of 12 to 9 out of 11 at a dose of 250 mg/kg DOX-GA3. At the
      higher prodrug dose (500 mg/kg) the number of regressions improved from 2 out of
      12 to 9 out of 10 as a result from the addition of enzyme-immunoconjugate. Our
      studies show that the efficacy of the widely used anti-cancer agent DOX may be
      improved by using the prodrug DOX-GA3, in combination with the tumor-specific
      enzyme-immunoconjugate 323/A3-mGUS and a conjugate clearing antibody.

PMID- 11251981
TI  - Quantification of tumor cell injury in vitro and in vivo using expression of
      green fluorescent protein under the control of the GADD153 promoter.
AB  - The GADD153 gene is strongly transcriptionally activated by many types of
      cellular injury and the magnitude of the change in GADD153 expression is
      proportional to the extent of damage. We developed a novel reporter system in
      which a chimeric gene containing the GADD153 promoter linked to the coding region
      of an enhanced green fluorescent protein (EGFP) gene was stably integrated into
      the genome of a clone of UMSCC10b head and neck carcinoma cells. Activation of
      the exogenous GADD153 promoter was quantified using flow cytometric measurement
      of EGFP expression following drug exposure. The exogenous GADD153 promoter in
      this clone was activated by N-methl-N'-nitro-N-nitrosoguanidine (MNNG) in a
      concentration-dependent manner with kinetics that closely paralleled perturbation
      of cell cycle phase distribution. EGFP expression was strongly activated by a
      variety of genotoxic agents including DNA cross-linking and methylating agents,
      oxygen free radicals, DNA intercalator, UV and gamma-radiation and hypoxia. When
      grown as a xenograft in nude mice, the stably transfected clone also demonstrated
      dose-dependent EGFP expression when measured 4 days after cisplatin treatment.
      The reporter system accurately categorized the relative potency of adducts
      produced by 6 related platinum-containing drugs. In conclusion, this reporter
      system can facilitate in vitro and in vivo screening for agents capable of
      producing cytotoxicity via a wide variety of different mechanisms, and can be
      utilized to investigate the relative potency of structurally related DNA adducts.

PMID- 11251982
TI  - Dietary antioxidant vitamins, retinol, and breast cancer incidence in a cohort of
      Swedish women.
AB  - Dietary antioxidant vitamins and retinol have been proposed to be protective
      against breast cancer on the basis of their ability to reduce oxidative DNA
      damage and their role in cell differentiation. Epidemiologic studies have not
      been convincing in supporting this hypothesis, but women with high exposure to
      free radicals and oxidative processes have not been specifically considered. We
      explored these issues in the Swedish Mammography Screening Cohort, a large
      population-based prospective cohort study in Sweden that comprised 59,036 women,
      40-76 years of age, who were free of cancer at baseline and who had answered a
      validated 67-item food frequency questionnaire. During 508,267 person-years of
      follow-up, 1,271 cases of invasive breast cancer were diagnosed. Cox proportional
      hazards models were used to obtain hazard ratios (HRs) and 95% confidence
      intervals (CIs). There was no overall association between intake of ascorbic
      acid, beta-carotene, retinol or vitamin E and breast cancer incidence. High
      intake of ascorbic acid was inversely related to breast cancer incidence among
      overweight women (HR=0.61; 95% CI 0.45-0.82, for highest quintile of intake among
      women with body mass index>25 kg/m(2)) and women with high consumption of
      linoleic acid (HR=0.72; 95% CI 0.52-1.02, for highest quintile of ascorbic acid
      intake and average consumption of more than 6 grams of linoleic acid per day).
      Among women with a body mass index of 25 or below, the hazard ratio for breast
      cancer incidence was 1.27 (95% CI 0.99-1.63), comparing the highest to the lowest
      quintile of ascorbic acid intake. Consumption of foods high in ascorbic acid may
      convey protection from breast cancer among women who are overweight and/or have a
      high intake of linoleic acid.

PMID- 11251984
TI  - Use of permanent hair dyes and bladder-cancer risk.
AB  - A population-based case-control study was conducted in Los Angeles, California,
      which involved 1,514 incident cases of bladder cancer and an equal number of age
      , sex- and ethnicity-matched controls. Information on personal use of hair dyes
      was obtained from 897 cases and their matched controls. After adjustment for
      cigarette smoking, a major risk factor for bladder cancer, women who used
      permanent hair dyes at least once a month experienced a 2.1-fold risk of bladder
      cancer relative to non-users (p for trend = 0.04). Risk increased to 3.3 (95% CI
      = 1.3-8.4) among regular (at least monthly) users of 15 or more years.
      Occupational exposure to hair dyes was associated with an increased risk of
      bladder cancer in this study. Subjects who worked for 10 or more years as
      hairdressers or barbers experienced a 5-fold (95% CI = 1.3-19.2) increase in risk
      compared to individuals not exposed.

PMID- 11251983
TI  - Plasma organochlorine levels and the risk of breast cancer: an extended follow-up
      in the Nurses' Health Study.
AB  - The environmental organochlorines 2,2-bis(p-chlorophenyl)1,1,1,trichloroethane
      (DDT) and polychlorinated biphenyls (PCBs) have been implicated as potential
      causes of female breast cancer. We continued follow-up of our 1997 case-control
      study nested in the Nurses' Health Study cohort, adding 143 postmenopausal cases
      and controls to the original 238 pairs, and examining specific PCB congeners for
      the first time. We measured plasma levels of 2,2-bis(p-chlorophenyl)ethylene
      (DDE), the major metabolite of DDT, and PCBs prospectively, comparing women who
      were diagnosed with breast cancer between 1 month and 4 years after blood
      collection with control women in whom breast cancer did not develop. Median
      concentrations of lipid-adjusted DDE, total PCBs, and PCB numbers 118, 138, 153
      and 180, assessed individually, were similar among the cases and controls. The
      multivariate relative risk of breast cancer for women in the highest quintile of
      exposure as compared with women in the lowest quintile was 0.82 for DDE (95%
      confidence interval [CI]: 0.49-1.37) and 0.84 for total PCBs (95% CI: 0.47-1.52),
      0.69 for PCB 118 (95% CI: 0.39-1.22), 0.87 for PCB 138 (95% CI: 0.50-1.50), 0.83
      for PCB 153 (95% CI: 0.47-1.48), and 0.98 for PCB 180 (95% CI: 0.55-1.75). Sub
      group analyses were also performed. Overall, our results do not support the
      hypothesis that exposure to DDT and PCBs increases the risk of breast cancer.

PMID- 11251985
TI  - Smoking associated with hormone receptor negative breast cancer.
AB  - Women who smoke have less favourable prognosis following breast-cancer diagnosis.
      Some studies suggest that this is due to a more advanced stage at diagnosis, on
      average. Our present aim was to assess whether smoking is associated with other
      prognostic markers as well, e.g., hormone receptor status, histopathology and
      tumour differentiation. The evaluation was based on 268 incident cases in a
      cohort of 10,902 women (35% smokers) followed for an average of 12.4 years. An
      immunohistochemical method on recuts of tumour tissue was used to assess hormone
      receptor status. One pathologist classified all tumours according to the WHO
      system, Nottingham grade and Nottingham Prognostic Index. The relative risk (RR)
      of oestrogen receptor-negative tumours was, for current smokers, 2.21 [95%
      confidence interval (CI) 1.23-3.96] and, for ex-smokers, 2.67 (95% CI 1.41-5.06)
      compared to never-smokers. Ex-smokers had an increased risk of progesterone
      receptor-negative tumours (RR = 1.61, 95% CI 1.07-2.41), but there were no other
      significant associations between smoking habits and oestrogen receptor-positive
      or progesterone receptor-positive or -negative tumours. The incidence of
      Nottingham grade III tumours was higher in ex-smokers than in never-smokers (RR =
      2.03, 95% CI 1.17-3.54). In terms of histopathological type or Nottingham
      Prognostic Index, there were no significant differences between smoking groups.
      We conclude that smoking is associated with an increased occurrence of hormone
      receptor-negative tumours.

PMID- 11251987
TI  - Kaposi's sarcoma herpes virus and Kaposi's sarcoma in the elderly populations of
      3 Mediterranean islands.

PMID- 11251986
TI  - Long-term tobacco smoking and colorectal cancer in a prospective cohort study.
AB  - Tobacco smoking has consistently been associated with colorectal adenomas,
      precursors of cancer, but the association with colorectal cancer itself has not
      been consistent. If colorectal cancer emerges only after a 35-year induction
      period, an association would unlikely be detected in studies where exposure
      assessment is of shorter duration. Most previous studies do not examine smoking
      of such duration and therefore do not account for the hypothesized 35-year
      induction period. By using the Cox proportional hazards models to estimate
      relative risks, we studied the association of long-term smoking and colorectal
      cancer risk in a population-based prospective cohort of 17,118 Swedish twins with
      up to 30 years of follow-up and information on smoking habits prior to baseline
      exposure assessment. Long-term heavy smoking was associated with a statistically
      significant 3-fold increased risk of colorectal cancer compared with never
      smoking (relative risk 3.1, 95% CI 1.4- 7.1). Examining colorectal cancer sub
      sites separately, a non-significant 60% increased risk of colon cancer was
      observed only for heavy smokers and a statistically significant 5-fold increased
      risk was observed for rectal cancer. Our data lend some support to the hypothesis
      that heavy long-term cigarette smoking is associated with increased risk of
      colorectal cancer. Further elucidation of this association would be valuable from
      both etiologic and public health perspectives.

PMID- 11251988
TI  - Paan without tobacco: an independent risk factor for oral cancer.

PMID- 11251991
TI  - Exstrophy of the cloaca and the OEIS complex: one and the same.

PMID- 11251990
TI  - Exstrophy of the cloaca and exstrophy of the bladder: two different expressions
      of a primary developmental field defect.
AB  - Exstrophy of the bladder (EB) and exstrophy of the cloaca (EC) are generally
      recognizable as distinct clinical entities. In patients with EB, the posterior
      bladder wall is exposed through a midline defect of the abdomen. The umbilicus is
      inferiorly displaced and located close to the superior margin of the exstrophic
      bladder. Genital abnormalities are common in boys and girls who may present
      epispadias and a small, split phallus or a split clitoris, a bifid uterus, and a
      duplicate or exstrophic vagina. In contrast to classic EB, EC is commonly
      associated with omphalocele, spinal defects, and incompletely formed external
      genitalia and is always associated with imperforate anus. Some authors state that
      EC and EB constitute two distinct disorders, but others consider them part of a
      "continuum," representing different levels of severity within the same spectrum.
      The use of the acronym OEIS to refer to the combination of omphalocele,
      exstrophy, imperforate anus, and spinal defects, in our opinion, has not helped
      to clarify the clinical definition, pathogenesis, or cause of this multiple
      congenital anomaly (MCA) pattern, mostly because the term makes no distinction
      between EC or EB. Here we present the epidemiological analysis of a group of
      characteristics in infants with EC and infants with EB to determine if they
      constitute two different entities. We also analyze if the different combinations
      of omphalocele, imperforate anus, and spinal defects are more frequent in infants
      with EC than in infants with MCA patterns other than EC and EB. The prevalence in
      our data for EC was 1:200,233 live births and 1:35,597 for EB. The clinical
      analysis indicated that the study defects (omphalocele, spine defects, spina
      bifida, and imperforate anus) tend to occur together in the same child with a
      higher frequency if the child has the EC defect than in infants with MCA patterns
      that did not include EC or EB. Our findings of low birth weight, twinning, single
      umbilical artery, and preferentially associated malformations suggest that EC is
      the result of damage occurring very early in development and that EC and EB are
      two different expressions of a primary polytopic developmental field defect.

PMID- 11251993
TI  - Misclassification risk of patients with bilateral cleft lip and palate and
      manifestations of median facial dysplasia: A new variant of del(22q11.2)
      syndrome?
AB  - The generic term median facial dysplasia (MFD) describes a subgroup of patients
      with cleft lip and palate exhibiting characteristic craniofacial defects: (1)
      short prolabium, (2) absence of frenulum labii, (3) hypoplasia of premaxilla, (4)
      absent upper central and lateral incisors of the cleft side, and (5) deficient
      septal cartilage and nasal spine. Gross brain malformations are usually absent in
      MFD. The same craniofacial malformations are also described in patients with
      holoprosencephaly sequence (HPE-S). We report on two male patients with bilateral
      cleft lip and palate showing the facial findings of MFD or HPE-S. Additional
      congenital malformations were anal atresia in one patient and severe cardiac
      defect in the other. In both, HPE was excluded by brain imaging, although
      uncommon brain anomalies were detected consisting of multiple white-matter
      lesions in the one patient and unusual enlargement and tortuosity of
      intracerebral blood vessels in both patients. In addition to facial anomalies,
      the patients also had psychiatric problems typically seen in velo-cardio-facial
      syndrome (VCFS). Fluorescence in situ hybridization (FISH) analysis confirmed a
      22q11.2 microdeletion in both.

PMID- 11251992
TI  - OEIS complex (omphalocele-exstrophy-imperforate anus-spinal defects): a review of
      14 cases.
AB  - OEIS complex refers to a combination of defects consisting of omphalocele,
      exstrophy of the cloaca, imperforate anus, and spinal defects. Possible
      embryologic mechanisms proposed for these findings have included: a single defect
      of early blastogenesis or a defect of mesodermal migration during the primitive
      streak period. Fourteen cases with OEIS complex and related malformations were
      reviewed for demographic features, prenatal and family histories, and clinical,
      radiological and pathological findings including the frequency and types of
      associated anomalies. The pathogenetic mechanisms causing OEIS complex and
      related malformations, such as anorectal and spinal defects, are discussed. The
      findings in these cases illustrate the spectrum of defects that can occur in the
      embryologic development of the cloaca and the urorectal septum. Differences in
      the timing and extent of mesenchymal ingrowth as well as cloacal membrane rupture
      may account for these variable findings. A developmental field defect involving
      the intraembryonic mesoderm suggests a possible etiologic role for homeobox
      genes, such as HLXB9 with mutations, resulting in anorectal and spine
      abnormalities, or retinoic acid receptors. OEIS complex with its mostly sporadic
      occurrence suggests etiologic heterogeneity with a possible role for
      environmental and genetic causes.

PMID- 11251994
TI  - Bernard-Soulier syndrome associated with 22q11.2 microdeletion.
AB  - We describe a Japanese girl with Bernard-Soulier syndrome and 22q11.2
      microdeletion. She had viral infections and recurrent thrombocytopenia and
      hemorrhagic diathesis after cardiac surgery. As congenital heart defects and
      abnormal immunity are the most common clinical manifestations associated with
      22q11.2 deletion, patients with this association may have a greater risk of
      developing a severe bleeding disorder.

PMID- 11251995
TI  - Distinctive metaphyseal chondrodysplasia simulating cartilage hair hypoplasia.
AB  - We report on a 5(1/2) year-old Italian girl with a distinctive form of
      metaphyseal chondrodysplasia simulating cartilage hair hypoplasia. The pattern of
      metaphyseal changes and the associated bony abnormalities differentiate this
      patient from all the recognized forms of metaphyseal chondrodysplasia.

PMID- 11251996
TI  - Novel approach to the molecular diagnosis of Marfan syndrome: application to
      sporadic cases and in prenatal diagnosis.
AB  - Marfan syndrome is an autosomal dominant disorder affecting the skeletal, ocular,
      and cardiovascular systems. Defects in the gene that encodes fibrillin-1 (FBN1),
      the main structural component of the elastin-associated microfibrils, are
      responsible for the disorder. Molecular diagnosis in families with Marfan
      syndrome can be undertaken by using intragenic FBN1 gene markers to identify and
      track the disease allele. However, in sporadic cases, which constitute up to 30%
      of the total, DNA-based diagnosis cannot be performed using linked markers but
      rather requires the identification of the specific FBN1 gene mutation. Due to the
      size and complexity of the FBN1 gene, identification of a causative Marfan
      syndrome mutation is not a trivial undertaking. Herein, we describe a
      comprehensive approach to the molecular diagnosis of Marfan syndrome that relies
      on the direct analysis of the FBN1 gene at the cDNA level and detects both coding
      sequence mutations and those leading to exon-skipping, which are often missed by
      analysis at the genomic DNA level. The ability to consistently determine the
      specific FBN1 gene mutation responsible for a particular case of Marfan syndrome
      allows both prenatal and pre-implantation diagnosis, even in sporadic instances
      of the disease.

PMID- 11251998
TI  - Refined FISH characterization of a de novo 1p22-p36.2 paracentric inversion and
      associated 1p21-22 deletion in a patient with signs of 1p36 microdeletion
      syndrome.
AB  - We report on a 10-year-old boy presenting with obesity, moderate mental
      retardation, large anterior fontanelle at birth, mild physical anomalies
      including mid-face hypoplasia, deep-set eyes, long philtrum, and small mouth. He
      was found to carry a paracentric inversion inv(1)(p22p36.2) associated with a 10
      cM deletion at the proximal breakpoint. By YAC FISH, the boundaries of the
      deletion were established at IB1028 (1p21) and WI-5166 (1p22) STSs contained in
      YACs 781E8 and 954F6, respectively. This large region, covering about 10 cM,
      contains the COL11A1 and AMY2B genes, whose haploinsufficiency does not seem to
      contribute significantly to the clinical phenotype. On the other hand, the
      patient's clinical manifestations, also including visual problems and moderate
      mental retardation, are those typically observed in the 1p36 deletion syndrome.
      Refined mapping of the telomeric 1p36.2 inversion breakpoint was obtained by FISH
      of a PAC contig constructed to encompass this subinterval of the 1p36
      microdeletion syndrome region. PACs 1024B10 and 884E7 were found to span the
      breakpoint, suggesting that the clinical signs of the 1p36 microdeletion syndrome
      might be due to disruption of a sequence lying at 1p36.2.

PMID- 11251997
TI  - Mutations in the caveolin-3 gene: When are they pathogenic?
AB  - Limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of genetic
      disorders usually with autosomal recessive (AR) inheritance and, less often,
      displaying autosomal dominant (AD) inheritance. Mutations in the caveolin-3 gene
      (CAV-3) associated with a reduction of protein expression cause AD-LGMD1C
      muscular dystrophy. Based on a previous study in the American and Brazilian
      population, it has been suggested that CAV-3 mutations might also cause AR-LGMD.
      Here we report the analysis of the CAV-3 gene in 61 additional Brazilian LGMD
      patients and 100 additional Brazilian normal controls. Two rare G55S and C71W
      missense changes previously detected only in LGMD patients (and not detected in
      100 normal controls from the American population) were now found in normal
      Brazilian controls. In addition, we have identified a novel R125H missense change
      in one LGMD female patient that was also found in two of her unaffected siblings.
      These observations, together with the normal immunofluorescence caveolin pattern
      in the muscle biopsy from two patients with the G55W and R125H changes in the CAV
      3 gene suggest that the G55S, C71W, and R125H polymorphisms, on their own, are
      not sufficient to produce the pathology.

PMID- 11251999
TI  - Submicroscopic 8pter deletion, mild mental retardation, and behavioral problems
      caused by a familial t(8;20)(p23;p13).
AB  - Microscopically visible distal 8p deletions have been associated with growth and
      mental impairment, minor facial anomalies, congenital heart defects, and
      behavioral problems. We report two cousins with mild retardation and behavioral
      problems, including inappropriate sexual behavior and pyromania. Familial
      learning difficulties on the grandfather's side incompatible with Mendelian
      inheritance prompted telomere screening, which detected a submicroscopic terminal
      8p deletion of < 5.1 Mb. The cousins' mothers both carried a t(8;20)(p23;p13)
      balanced translocation. The frequently observed microcephaly in patients with
      microscopically visible deletions of 8pter is lacking in both cousins, suggesting
      that the gene(s) causing the microcephaly is centromeric to the deleted region.
      The absence of cardiac defects in the cousins confirms the more proximal location
      of gene(s) causing these abnormalities in other reported cases with
      microscopically visible 8pter deletions and supports involvement of the GATA4
      gene. Moreover, the current cases predict the presence of a putative gene(s)
      involved in behavior in the most telomeric 5.1 Mb of the p-arm of chromosome 8.
      This first clinical report of a submicroscopic subtelomeric 8p deletion gives
      more insight into the so-called 8p- syndrome and demonstrates the difficulty in
      making a clinical diagnosis for a submicroscopic 8pter deletion in an individual
      patient with mental retardation.

PMID- 11252000
TI  - Recurrent trisomy 15 in a female carrier of der(15)t(Y;15)(q12;p13).
AB  - We report on a female carrier of der(15) t(Y;15)(q12;p13) who had two pregnancy
      losses with trisomy 15 and one with tetraploidy. Molecular analysis showed that
      both non-disjunction events resulting in the trisomy 15 pregnancies occurred in
      maternal meiosis I. This finding raises the possibility that there may be an
      increased risk for trisomy 15 in some carriers of unbalanced t(Y;15) which, if
      followed by trisomic zygote rescue, may lead to uniparental disomy (UPD).

PMID- 11252001
TI  - High prevalence of complement C7 deficiency among healthy blood donors of
      Moroccan Jewish ancestry.
AB  - The incidence of the specific component deficiencies in various ethnic groups is
      not known, although there appears to be an ethnic predilection for C6 and C8alpha
      gamma deficiencies in blacks, whereas C7 and C8beta deficiencies are
      predominantly noted in Caucasians. Infectious diseases, particularly recurrent
      meningococcal infections, are observed more commonly with late component
      deficiencies. In the current study, we have simplified the PCR technique by using
      site-directed mutagenesis and designer primers in a cohort of Israeli Moroccan
      Jewish blood donors to ascertain allele frequency in this ethnic group, which,
      based on earlier studies, was considered to be at risk for C7 deficiency. The
      total mutant allele frequency in this ethnic cohort was 1.1% of a total of 365
      healthy Israeli Moroccan Jews, including one homozygote. The identification of
      mutant alleles was efficient and inexpensive, and hence a large cohort was
      studied. The finding of complement deficiency identifies individuals at risk for
      Neisserial infections, which are known to be potentially life-threatening.
      Conversely, when a patient of Moroccan ancestry is diagnosed with a Neisserial
      infection, it is important to determine the complement status.

PMID- 11252003
TI  - Terminal deletion of Xp22.3 associated with contiguous gene syndrome: Leri-Weill
      dyschondrosteosis, developmental delay, and ichthyosis.

PMID- 11252002
TI  - Loss of the SEDL gene product (Sedlin) causes X-linked spondyloepiphyseal
      dysplasia tarda: Identification of a molecular defect in a Japanese family.
AB  - A 23-year-old man was diagnosed as having X-linked spondyloepiphyseal dysplasia
      tarda (SEDT; MIM 313400) based on his disproportionately short trunk, short
      stature, characteristic radiological features of the spine (posterior hump, end
      plate sclerosis, and disc space narrowing) and the hips (short and thick femoral
      necks), and positive family history. This Japanese family was found to have an
      intragenic deletion flanking intron 2 and exon 3 of the SEDL gene that not only
      included the 5' untranslated region but also the coding sequence for the first
      methionine through the 25th alanine. This mutation was present in the proband and
      his unaffected mother (a heterozygote), but not in an unaffected sister and an
      unaffected uncle. The nature of the mutation predicted that the SEDL protein
      (Sedlin) was not produced in the proband, indicating that loss of Sedlin caused
      SEDT.

PMID- 11252004
TI  - No evidence of dup(7)(p11.2p13) in Silver-Russell syndrome.

PMID- 11252005
TI  - First known microdeletion within the Wolf-Hirschhorn syndrome critical region
      refines genotype-phenotype correlation.
AB  - Deletions within HSA band 4p16.3 cause Wolf-Hirschhorn syndrome (WHS), which
      comprises mental retardation and developmental defects. A WHS critical region
      (WHSCR) of approximately 165 kb has been defined on the basis of 2 atypical
      interstitial deletions; however, genotype-phenotype correlation remains
      controversial, due to the large size of deletion usually involving several
      megabases. We report on the first known patient with a small de novo interstitial
      deletion restricted to the WHSCR who presented with a partial WHS phenotype
      consisting only of low body weight for height, speech delay, and minor facial
      anomalies; shortness of stature, microcephaly, seizures and mental retardation
      were absent. The deletion was initially demonstrated by FISH analysis, and
      breakpoints were narrowed with a "mini-FISH" technique using 3-5 kb amplicons. A
      breakpoint-spanning PCR assay defined the distal breakpoint as disrupting the
      WHSC1 gene within intron 5, exactly after an AluJb repeat. The proximal
      breakpoint was not found to be associated with a repeated sequence or a known
      gene. The deletion encompasses 191.5 kb and includes WHSC2, but not LETM1. Thus,
      manifestations attributable to this deletion are reduced weight for height, minor
      facial anomalies, ADHD and some learning and fine motor deficiencies, while
      seizures may be associated with deletions of LETM1.

PMID- 11252006
TI  - A comparison of statistical methods for meta-analysis.
AB  - Meta-analysis may be used to estimate an overall effect across a number of
      similar studies. A number of statistical techniques are currently used to combine
      individual study results. The simplest of these is based on a fixed effects
      model, which assumes the true effect is the same for all studies. A random
      effects model, however, allows the true effect to vary across studies, with the
      mean true effect the parameter of interest. We consider three methods currently
      used for estimation within the framework of a random effects model, and
      illustrate them by applying each method to a collection of six studies on the
      effect of aspirin after myocardial infarction. These methods are compared using
      estimated coverage probabilities of confidence intervals for the overall effect.
      The techniques considered all generally have coverages below the nominal level,
      and in particular it is shown that the commonly used DerSimonian and Laird method
      does not adequately reflect the error associated with parameter estimation,
      especially when the number of studies is small.

PMID- 11252007
TI  - The sample size for a clinical trial: a Bayesian-decision theoretic approach.
AB  - Using decision theory, what is an appropriate sample size for a clinical trial,
      with a binary endpoint? We present a program, suitable for actual planning,
      which, with some extensions, implements Canner's solution to this question.
      Examples with a discussion are given. Implications of a Bayesian approach are
      discussed. Bayesian and Neyman--Pearson approaches are compared.

PMID- 11252008
TI  - Sample size tables for exact single-stage phase II designs.
AB  - Tables for single-phase II trials based on the exact binomial distribution are
      presented. These are preferable to those generated using Fleming's design, which
      are based on the normal approximation and can give rise to anomalous results. For
      example, if the upper success rate is accepted, the lower success rate, which the
      trial is designed to reject, may be included in the final confidence interval for
      the proportion being estimated.

PMID- 11252009
TI  - Heterogeneity in phase I clinical trials: prior elicitation and computation using
      the continual reassessment method.
AB  - Heterogeneity in a phase I clinical trial patient population may lead to
      distinctly different dose-response relationships along covariate values. For a
      given target probability of toxicity, this implies different maximum tolerated
      doses (MTDs) for each distinct subpopulation. Within the framework of O'Quigley,
      Pepe and Fisher's (1990) continual reassessment method, we propose the notion of
      average and patient-specific MTDs by augmenting the dose--response model with
      other covariates to account for such differences. A method to elicit prior
      distributions on the dose and other covariate parameters are proposed, based on
      the predictive approach of Ibrahim and Laud (1994), Laud and Ibrahim (1995), and
      Ibrahim, Ryan and Chen (1998). This approach relies on prior predictions for the
      response vector y(0) and a quantity a(0) specifying uncertainty in y(0). Then,
      y(0) and a(0) are used to specify a prior for the regression coefficients in a
      semi-automatic fashion. The elicitation scheme for y(0) uses results from
      previous phase I cancer clinical trials. The average and patient-specific MTDs
      and an elicitation method are demonstrated in logistic regression examples.

PMID- 11252011
TI  - Estimating the number needed to treat (NNT) index when the data are subject to
      error.
AB  - The number needed to treat (NNT) index has been proposed as a clinically useful
      measure to assess the results of randomized trials and other clinical studies. In
      its usual form, NNT indicates the expected number of patients who must be treated
      with an experimental therapy in order to prevent one adverse event, compared to
      the expected event rates under the control therapy. It can be formulated as a
      function of the proportions of patients who respond to treatment by more than a
      certain amount, the clinically important difference. We may also wish to evaluate
      two group studies comparing treatment and control responses, and to consider net
      benefit from treatment (by also allowing for individuals who deteriorate as well
      as those who respond positively). In this paper, we investigate the effect on NNT
      caused by measurement errors in continuous outcome measures. Such errors can lead
      to bias in the estimated proportions of subjects with clinically important
      responses, and hence bias the associated values of NNT. General expressions for
      the bias are derived, and enumerated for typical scenarios. For many situations,
      reliability of 80 per cent or more in the observations is required to restrict
      the bias to tolerable levels.

PMID- 11252010
TI  - A standardization method to adjust for the effect of patient selection in phase
      II clinical trials.
AB  - New combination regimens evaluated in phase II cancer clinical trials often show
      promising results compared to the standard therapy for a disease system.
      Selection of patients with a better prognosis can be a prominent factor for this
      optimism. For most disease systems, prognostic variables that are related to the
      outcome are available and are called risk factors. Patients are classified into
      risk categories depending on the number of risk factors they possess. The patient
      distribution is defined as the proportion of patients falling into each of these
      risk categories. Typically, the patient distribution observed for a phase II
      study differs from the standard therapy reports so that the outcomes are not
      comparable. A randomized trial is the ultimate step for establishing the efficacy
      of a new treatment. In order to determine whether a regimen should progress to a
      phase III trial, we suggest adjusting the standard therapy outcome for the effect
      of the observed phase II patient distribution. If the endpoint of interest is
      tumour response proportion, a weighted average utilizing the standard therapy
      response proportions and the phase II patient distribution would provide an
      estimate of the adjusted standard therapy response proportion. Confirmatory phase
      II trials often attempt to estimate median survival in addition to response
      proportion, since this is the primary endpoint for most phase III cancer studies.
      Because data are censored, we propose an adjustment method based on the bootstrap
      resampling technique. We illustrate the problem of disparate patient selection
      with data from melanoma studies and demonstrate the usefulness of the proposed
      adjustment method with data from bladder cancer studies. A simulation study
      indicates that the magnitude of the adjustment is heavily dependent on the degree
      of separation of the risk categories. SAS code is available on a website
      (http://lib.stat.cmu.edu) for easy implementation.

PMID- 11252013
TI  - Testing for elevated disease rates using smoothed estimates.
AB  - A method of testing for elevated disease rates using smoothed estimates is
      introduced for counts aggregated to a specific administrative level. A test
      statistic is developed based on an approximation to the smoothed estimate from a
      penalized multinomial likelihood and an approximate critical value is derived.
      Empirical investigation reveals that smoothing can increase the ability to detect
      elevated rates. The methods are applied to data on gastric cancer in Nova Scotia,
      Canada.

PMID- 11252012
TI  - Simultaneous comparison of sensitivity and specificity of two tests in the paired
      design: a straightforward graphical approach.
AB  - Often the performances of two binary diagnostic or screening tests are compared
      by applying them to the same set of subjects, some of whom are affected, some
      unaffected. The McNemar test, and corresponding interval estimation methods, may
      be used to compare the sensitivity of the two tests, but this disregards both any
      observed difference in specificity and its imprecision due to sampling variation.
      The suggested approach is to display point and interval estimates for a weighted
      mean f of the differences in sensitivity and specificity between the two tests.
      The mixing parameter lambda, which is allowed to range from 0 to 1, represents
      the prevalence in the population to which application is envisaged, together with
      the relative seriousness of false positives and false negatives. The confidence
      interval for f is obtained by a simple extension of a closed-form method for the
      paired difference of proportions, which has favourable coverage properties and is
      based on the Wilson single proportion score method. A plot of f against lambda is
      readily obtained using a Minitab macro.

PMID- 11252014
TI  - Estimating prevalence when the true disease status is incompletely ascertained.
AB  - We discuss the problem of estimating the number of cases not identified in
      studies of two or more screening tests in which not all individuals are fully
      evaluated. In particular we consider studies in which only those individuals who
      are positive on a screening test have a complete diagnosis. We show how to adjust
      for individuals who are not fully evaluated despite recommendation for referral
      and for cases not identified among those negative on all screening tests. The
      assumptions under which these adjustments are valid are discussed. A proposal is
      made for analysis of studies using three screening tests. Estimation of and
      inference about the disease prevalence and the test sensitivity when disease
      status is ascertained on a random sample of those negative on both screening
      tests is discussed.

PMID- 11252015
TI  - Repeated-measures models to evaluate a hepatitis B vaccination programme.
AB  - In 1985-1986, a hepatitis B vaccination programme was conducted in a Belgian
      institution for the mentally handicapped. A group of 97 residents was followed up
      for 11 years in order to characterize the long-term persistence of hepatitis B
      antibodies after vaccination. This paper proposes the use of linear mixed-effects
      models to account for serial correlation and between-individual heterogeneity in
      the data, while adjusting the analysis for various individual characteristics and
      important risk factors in the response to vaccination. We propose several model
      building strategies and focus on the prediction of future levels of antibodies.

PMID- 11252016
TI  - Assessing human fertility using several markers of ovulation.
AB  - In modelling human fertility one ideally accounts for timing of intercourse
      relative to ovulation. Measurement error in identifying the day of ovulation can
      bias estimates of fecundability parameters and attenuate estimates of covariate
      effects. In the absence of a single perfect marker of ovulation, several error
      prone markers are sometimes obtained. In this paper we propose a semi-parametric
      mixture model that uses multiple independent markers of ovulation to account for
      measurement error. The model assigns each method of assessing ovulation a
      distinct non-parametric error distribution, and corrects bias in estimates of day
      specific fecundability. We use a Monte Carlo EM algorithm for joint estimation of
      (i) the error distribution for the markers, (ii) the error-corrected fertility
      parameters, and (iii) the couple-specific random effects. We apply the methods to
      data from a North Carolina fertility study to assess the magnitude of error in
      measures of ovulation based on urinary luteinizing hormone and metabolites of
      ovarian hormones, and estimate the corrected day-specific probabilities of
      clinical pregnancy. Published in 2001 by John Wiley & Sons, Ltd.

PMID- 11252017
TI  - Methods of adjustment for estimating the attributable risk in case-control
      studies: a review, by Jacques Benichou, Statistics in Medicine 1991; 10:1753
      1773.

PMID- 11252020
TI  - Effects of lubeluzole on the methamphetamine-induced increase in extracellular
      glutamate and the long-term depletion of striatal dopamine.
AB  - The administration of a neurotoxic regimen of methamphetamine (MA) produces an
      acute elevation in the extracellular concentrations of dopamine and glutamate in
      the striatum and a long-term depletion of striatal dopamine content in rats. The
      intent of the present study was to determine whether attenuation of the MA
      induced increase in extracellular glutamate would prevent the depletion of
      striatal dopamine. Male rats were treated with MA (10 mg/kg, i.p.) or vehicle
      every 2 h for four injections and concomitantly perfused intrastriatally with
      either artificial cerebrospinal fluid or lubeluzole (300 microM), a novel
      neuroprotectant that has been shown to prevent the increase in extracellular
      glutamate after the induction of neocortical infarct in rats. Lubeluzole
      significantly attenuated the MA-induced increase in extracellular glutamate in
      the striatum without affecting the MA-induced increase in extracellular dopamine
      or the MA-induced hyperthermic response. Nevertheless, lubeluzole did not prevent
      the long-term depletion of striatal dopamine produced by a neurotoxic regimen of
      MA. These results suggest that the MA-induced depletion of striatal dopamine may
      not be dependent on the increased extracellular concentration of striatal
      glutamate.

PMID- 11252021
TI  - Acute and repeated administration of the selective 5-HT(2A) receptor antagonist
      M100907 significantly alters the activity of midbrain dopamine neurons: an in
      vivo electrophysiological study.
AB  - We examined the effect of the acute and repeated administration of M100907
      (formerly MDL 100907), a selective 5-HT(2A) receptor antagonist, on spontaneously
      active dopamine (DA) neurons in the substantia nigra pars compacta (SNC) and
      ventral tegmental area (VTA) of rats. This was accomplished using in vivo,
      extracellular single unit recording. The i.v. administration of M100907 (0.01
      0.64 mg/kg) did not significantly alter the basal firing rate or pattern of
      spontaneously active SNC and VTA DA neurons. A single injection of either 0.01 or
      0.03 mg/kg i.p. of M100907 did not significantly alter the number of
      spontaneously active DA neurons in either the SNC or VTA areas. However, 0.1
      mg/kg i.p. of M100907 significantly increased the number of spontaneously active
      SNC and VTA DA neurons compared to vehicle-treated animals. A single injection of
      all doses of M100907 significantly decreased the degree of bursting in VTA DA
      neurons, whereas the 0.1 mg/kg dose increased the degree of bursting in SNC DA
      neurons. The repeated administration (one injection per day for 21 days) of 0.03
      and 0.1 mg/kg i.p. of M100907 produced a significant decrease in the number of
      spontaneously active SNC and VTA DA neurons compared to vehicle-treated animals.
      The repeated administration of M100907 did not significantly alter the firing
      pattern of VTA DA neurons but significantly altered the firing pattern of SNC DA
      neurons. The results of this study indicate that M100907 administration alters
      the activity of midbrain DA neurons in anesthetized rats.

PMID- 11252022
TI  - Long-term impairment of anterograde axonal transport along fiber projections
      originating in the rostral raphe nuclei after treatment with fenfluramine or
      methylenedioxymethamphetamine.
AB  - To further evaluate the serotonin (5-HT) neurotoxic potential of substituted
      amphetamines, we used tritiated proline to examine anterograde transport along
      ascending axonal projections originating in the rostral raphe nuclei of animals
      treated 3 weeks previously with (+/-)fenfluramine (FEN, 10 mg/kg, every 2 h x 4
      injections; i.p.) or (+/-)3,4-methylenedioxymethamphetamine (MDMA, 20 mg/kg,
      twice daily for 4 days; s.c.). The documented 5-HT neurotoxin, 5,7
      dihydroxytryptamine (5,7-DHT, 75 microg; ICV; 30 min after pretreatment with
      pargyline, 50 mg/kg; i.p., and desipramine 25 mg/kg; i.p.), served as a positive
      control. Along with anterograde axonal transport, we measured two 5-HT axonal
      markers, 5-HT and 5-hydroxyindoleacetic acid (5-HIAA). Prior treatment with FEN
      or MDMA led to marked reductions in anterograde transport of labeled material to
      various forebrain regions known to receive 5-HT innervation. These reductions
      were associated with lasting decrements in 5-HT axonal markers. In general,
      decreases in axonal transport were less pronounced than those in 5-HT and 5-HIAA.
      However, identical changes were observed after 5,7-DHT. These results further
      indicate that FEN and MDMA, like 5,7-DHT, are 5-HT neurotoxins.

PMID- 11252023
TI  - In vivo binding properties of [carbonyl-11C]WAY-100635: effect of endogenous
      serotonin.
AB  - [Carbonyl-(11)C]WAY-100635 has been reported to be a useful ligand for the
      investigation of 5-HT(1A) receptor imaging in vivo. However, the cellular
      distribution and the influence of endogenous serotonin (5-HT) on in vivo binding
      have not been fully examined. In this study, we investigated the effect of 5,7
      dihydroxytryptamine-produced destruction of 5-HT neurons, reserpine-induced 5-HT
      depletion, and fenfluramine-induced 5-HT increase on [carbonyl-(11)C]WAY-100635
      binding in vivo. There was no significant change in the uptake of [carbonyl
      (11)C]WAY-100635 in the slice of 5-HT denervated rat brain except in the raphe
      nucleus, where 5-HT cell bodies exist. There was no obvious effect of enhanced 5
      HT release by fenfluramine or decreased release by reserpine on [carbonyl
      (11)C]WAY-100635 binding in the dissected brain region. No significant effect was
      observed in the time course of [carbonyl-(11)C]WAY-100635 in the hippocampus and
      frontal cortex measured by PET. These results indicated that the in vivo binding
      of [carbonyl-(11)C]WAY-100635 in the hippocampus and cerebral cortex mainly
      reflects postsynaptic 5-HT(1A) receptor binding, and that this binding is not
      sensitive to endogenous 5-HT.

PMID- 11252024
TI  - Influence of restraint stress on the expression and the serine/threonine
      phosphatase activity of calcineurin in the rat brain.
AB  - To investigate the role of calcineurin (CaN) in the pathogenesis of stress
      related psychiatric disorders, we examined the expression of CaN A mRNA and the
      serine/threonine phosphatase activity of CaN in the rat brain following various
      restraint stress paradigms. Northern blot analysis revealed no significant
      changes in the levels of CaN A mRNA expression, in either the frontal cortex or
      the hippocampus, in response to a single restraint stress for either 15, 45, or
      90 min. In addition, no significant change in the levels of CaN A mRNA was found
      3 or 6 h after a single restraint stress for 90 min. In situ hybridization
      analysis revealed that a single restraint stress for 45 min had no influence on
      CaN A mRNA expression in the CA1 and CA3 pyramidal cell layers or in the dentate
      gyrus granule cell layer of the hippocampus. However, serine/threonine
      phosphatase activity was significantly increased in both regions in response to a
      single restraint stress for either 45 or 90 min. These results demonstrate that
      the single restraint stress paradigms used in this study increase the activity of
      CaN without any changes in the expression of CaN, suggesting that the activation
      of calmodulin and the increased levels of heat shock proteins in response to the
      restraint stress may upregulate the activity of CaN in the rat brain.

PMID- 11252025
TI  - D2 but not D3 receptors are elevated after 9 or 11 months chronic haloperidol
      treatment: influence of withdrawal period.
AB  - Previous postmortem studies have identified divergent alterations in D2 and D3
      receptors in schizophrenia but those results cannot be interpreted without
      further understanding of whether antipsychotic regulation of the D3 receptor is
      different from that of the D2 receptor. Depot parenteral administration of
      haloperidol decanoate was utilized to achieve consistent high levels in rat brain
      for 9 months with 2-month withdrawal or 11 months with 48-h withdrawal and
      compared to vehicle control and acute haloperidol (48-h) treatment groups.
      Autoradiographic means for measuring levels of D2 ([(3)H]-spiperone) and D3
      receptors ([(125)I]trans 7-OH-PIPAT) and of D3 mRNA by in situ hybridization
      histochemistry in rat caudate-putamen, nucleus accumbens, islands of Calleja, and
      olfactory tubercle determined that there were significant group differences for
      regulation of D2 receptor. Chronic haloperidol for 9 or 11 months elevated D2 but
      not D3 receptors or D3 mRNA in all regions measured. Acute haloperidol treatment
      had no significant effects for any measure. Treatment for 9 months with a 2-month
      withdrawal resulted in a persistent increase in D2 receptors that was greater
      than that observed in the 11 months with 48-h withdrawal. This effect was most
      noticeable in the olfactory tubercle. These data confirm previous findings that
      short- or long-term haloperidol treatment leads to elevations in D2 but not D3
      receptors or D3 mRNA, and long-term withdrawal from chronic haloperidol does not
      lead to elevations in D3 receptors or D3 mRNA. This suggests that an elevation in
      D3 receptors identified at postmortem in schizophrenics withdrawn from
      antipsychotics is not the result of the previous drug history [Gurevich et al.
      (1997) Arch Gen Psychiatry 54:225-232].

PMID- 11252026
TI  - Intrasubthalamic injection of 6-hydroxydopamine induces changes in the firing
      rate and pattern of subthalamic nucleus neurons in the rat.
AB  - The subthalamic nucleus (STN) receives dopaminergic projections from the
      substantia nigra pars compacta (SNc). To investigate the role of direct and
      indirect dopaminergic influences on STN neurons, the spontaneous activity was
      studied in four groups of animals: normal rats, rats with intrasubthalamic or
      intranigral injection of 6-hydroxydopamine (6-OHDA), and sham STN injection rats
      by using extracellular recordings 4 weeks postsurgery. After intrasubthalamic
      injection of 6-OHDA, the mean firing rate significantly decreased (7.29 +/- 0.39
      spikes/sec, P < 0.01 vs. 11.13 +/- 0.59 spikes/sec in normal or 11.26 +/- 0.57
      spikes/sec in sham group), and the percentage of STN neurons discharging
      regularly decreased significantly (81%, P < 0.05 vs. 90% in normal group or P <
      0.01 vs. 92% in sham group) and that of bursty cells increased (19%, P < 0.05 vs.
      10%; in normal group or P < 0.01 vs. 8% in sham group). In the group of rats with
      SNc lesion, the firing rate of subthalamic neurons did not show a significant
      difference (11.61 +/- 0.81 spikes/sec) compared with normal group. However, the
      firing pattern was dramatically changed: 74% of cells exhibited bursty pattern
      and only 26% of cells discharged regularly or slightly irregularly.
      Immunohistochemical results showed that intrasubthalamic injection of 6-OHDA
      induced a marked degeneration of dopaminergic cells in the lateral part of the
      ipsilateral SNc, whereas 6-OHDA injection into the SNc induced a total in situ
      lesion of dopamine cells. These results suggest that the SNc exerts an excitatory
      influence on STN neurons and that the loss of this dopaminergic projection could,
      at least partially, account for the changes in the firing pattern of STN neurons
      in the 6-OHDA rat model of parkinsonism.

PMID- 11252028
TI  - Non-invasive tumour blood perfusion measurement by 2H magnetic resonance.
AB  - Deuterium uptake into foot-implanted C3H murine mammary carcinomas was measured
      non-invasively by 2H NMR spectroscopy at 46 MHz after i.v. injection. The
      arterial input function (AIF) was estimated from 2H NMR measurements with a
      second radiofrequency coil externally located over the heart. Tumour and heart
      data were acquired over the same time period by means of a switch automatically
      activated every 1.6-3.2 s. Although the AIF data were, in general, partly
      contaminated by signals from adjacent tissue, a mathematical fitting procedure
      involving simultaneous fitting of the AIF and the tumour kinetics gave robust
      results for tumour blood perfusion (TBP): up to four repeat TBP measurements were
      made in 14 out of 20 untreated animals and TBP could be measured before and after
      treatment in 14 out of 15 animals. The ability of this technique to measure
      changes in blood perfusion was assessed using hydralazine, which decreased TBP
      from 91 to 29 ml 100 g(-1) min(-1) and this was comparable to a 70% reduction in
      relative TBP measured by laser Doppler flowmetry.

PMID- 11252027
TI  - Member of the Ampakine class of memory enhancers prolongs the single channel open
      time of reconstituted AMPA receptors.
AB  - Ampakines are small benzamide compounds that allosterically produce the positive
      modulation of AMPA receptors and improve performance on a variety of behavioral
      tasks. To test if the native synaptic membrane is necessary for the effects of
      such positive modulators, the mechanism of action of the Ampakine 1-(1,3
      benzodioxol-5-ylcarbonyl)-1,2,3,6-tetrahydropyridine (CX509) was investigated in
      isolated rat brain AMPA receptors reconstituted in lipid bilayers. The drug
      increased the open time of AMPA-induced single channel current fluctuations with
      an EC(50) of 4 microM. The action of CX509 was highly selective since it had no
      effect on the amplitude or close time of channel events. The open time effect had
      a maximum enhancement of 70-fold and the modulated currents were blocked by CNQX.
      It is concluded that the synaptic membrane environment is not necessary for
      Ampakine effects. In fact, CX509 was about 100 times more potent on the
      reconstituted AMPA receptors than on receptors in their native membrane. These
      findings indicate that centrally active Ampakines modulate specific kinetic
      properties of AMPA currents. They also raise the possibility that AMPA receptors
      are regulated by factors present in situ, thus explaining the more efficient
      modulatory effects of CX509 when acting on receptors removed from their synaptic
      location.

PMID- 11252029
TI  - NMR studies on energy metabolism of immobilized primary neurons and astrocytes
      during hypoxia, ischemia and hypoglycemia.
AB  - Changes in high-energy phosphate metabolites (ATP and phosphocreatine) were
      monitored, in real time, by 31P-nuclear magnetic resonance in primary cell
      cultures of neurons and astrocytes during periods of hypoxia, ischemia and
      hypoglycemia, and also during the recovery periods following the re-establishment
      of standard conditions. Cells were immobilized in basement membrane gel threads
      and perfused with oxygen-depleted medium (oxygen concentration below 30 microM),
      to create hypoxic conditions, or with aerobic medium (oxygen concentration
      approximately 460 microM) containing different concentrations of glucose
      (hypoglycemia). Ischemic conditions were imposed by stopping perfusion for
      different periods of time (15 min to 2 h). The experimental set-up enabled the
      acquisition of 31P-spectra with high signal-to-noise ratio within 10-20 min for
      both cell types. The effect of hypoxia on glucose metabolism was assessed by 13C
      NMR using [1-13C]glucose as substrate. The levels of ATP and PCr in astrocytes
      were unaffected during hypoxia (up to 2 h), but decreased notably under ischemia.
      In neurons, hypoxic periods caused a sharp drop of the ATP and PCr levels, and
      considerable damage to the capacity of neurons to replenish the ATP and PCr pools
      upon returning to normoxic conditions. However, neurons were remarkably less
      sensitive to ischemic conditions, the ATP and PCr pools being restored quickly,
      even after 2 h under challenging conditions. The data show that neurons were more
      resistant to ischemia than astrocytes, and suggest that the capacity to sustain
      the pools of ATP and PCr was part of the neuronal protective strategy.

PMID- 11252030
TI  - Combined proton MR spectroscopy and dynamic contrast enhanced MR imaging of human
      intracranial tumours in vivo.
AB  - A study was undertaken to determine if the vascular characteristics measured by
      dynamic contrast-enhanced magnetic resonance imaging (primarily permeability
      surface area product and extracellular-extravascular tissue volume fraction)
      would be beneficial in explaining the inter-lesion metabolic heterogeneity
      displayed by human intracranial tumours. Magnetic resonance spectroscopy was
      carried out using a single-voxel STEAM sequence and dynamic imaging was carried
      out using a combination of pre-contrast proton density-weighted FSPGR images (to
      remove the influence of native tissue T1), bolus injection of Gd-DTPA and
      subsequent T1-weighted FSPGR dynamic imaging. A two-compartment pharmacokinetic
      model was employed to determine vascular characteristics. Results obtained from
      12 meningiomas suggest a possible correlation between the level of
      lipids/macromolecules and permeability surface area product, although the
      confounding issue of extra-voxel contamination arising from lipids in the scalp
      and skull marrow cannot be ruled out in the more superficial lesions. Results
      obtained from 11 gliomas (four low and seven high grade) demonstrate that
      permeability surface area product is not specific for the range of vascular
      characteristics and metabolite profiles observed in gliomas and is therefore
      unable to explain metabolic heterogeneity in these lesions.

PMID- 11252031
TI  - Simultaneous measurements of temperature and pH in vivo using NMR in conjunction
      with TmDOTP5-.
AB  - NMR techniques for temperature and pH measurements have attracted increasing
      interest in recent years, motivated in part by the growing importance of medical
      hyperthermia for the treatment of cancer. The chemical shifts of thulium 1, 4, 7,
      10-tetraazacyclododecane-1, 4, 7, 10-tetrakis(methylene phosphonate) (TmDOTP5-)
      have been studied as a function of temperature and pH. The results demonstrate
      that TmDOTP5- resonance shifts are highly sensitive to temperature (approximately
      1.0 ppm/degrees C) and pH (approximately 3.2 ppm/pH unit) at clinically relevant
      field strengths. A new method is presented which utilizes two magnetically non
      equivalent protons in TmDOTP5- for simultaneous NMR measurements of both
      temperature and pH. The difference in the chemical shift values of pairs of 1H
      resonances provides a temperature sensitivity of about 1.6 ppm/ degrees C. The
      technique is demonstrated in live rats undergoing ultrasound-induced hyperthermia
      therapy.

PMID- 11252032
TI  - Detection and quantification of free cytosolic inorganic phosphate and other
      phosphorus metabolites in the beating mouse heart muscle in situ.
AB  - The aim of this study was the quantification of inorganic phosphate (Pi) and
      other phosphorus metabolites by (31)P NMR spectroscopy in the mouse heart muscle
      in situ, beating at around 600 min(-1). Male adult Quacker-bush mice (mean weight
      32 +/- 7 g) were anaesthetized, ventilated and placed in a temperature-controlled
      animal holder. A purpose-built (31)P NMR surface coil was positioned against the
      exposed left ventricular myocardium. Partial signal overlap of Pi with 2,3-DPG
      from chamber blood was minimized using a DEPTH pulse sequence (180 degrees -90
      degrees -180 degrees -180 degrees -acq.). Quantification of phosphorus
      metabolites was performed using an external standard positioned directly above
      the surface coil. We report for the mouse myocardium in situ an intracellular
      free [Pi] of <0.4 mM, pH of 7.32 +/- 0.1, free [Mg2+] of 0.41 +/- 0.1 mM, free
      [ADP] of 13 +/- 1.5 microM, [ATP] of 5 +/- 0.5 mM and [PCr] of 14 +/- 1.5 mM. The
      phosphorylation ratio (ATP/ADP Pi) was 1005 +/- 200 mM (-1) for a PCr/ATP ratio
      of 2.7 +/- 0.3. It was concluded that the detection of free [Pi] in the mouse
      myocardium in situ can be greatly enhanced using a DEPTH pulse sequence.
      Quantification of compounds using an external standard positioned directly above
      the surface coil gave comparable results to estimations using internal ATP that
      was quantified enzymatically. The close agreement between the external and
      internal methods indicates that ATP is 100% NMR visible in the mouse heart in
      situ.

PMID- 11252034
TI  - Magnetic coupling between water and creatine protons in human brain and skeletal
      muscle, as measured using inversion transfer (1)H-MRS.
AB  - Using the inversion transfer technique, the possible magnetic coupling between
      water protons and the protons of low-molecular weight metabolites was
      investigated in human brain and skeletal muscle at 1.5 T. The localized (1)H-MR
      spectra were recorded at different times after selective inversion of the water
      resonance. Water inversion led to a significant transient reduction in the signal
      intensity of the methyl protons of creatine/phosphocreatine, in both tissues.
      This is indicative of magnetic coupling between the protons of water and those of
      creatine/phosphocreatine. Neither the choline and N-acetylaspartate protons in
      brain nor the protons of the trimethylammonium pool in skeletal muscle showed a
      significant magnetic coupling to mobile water.

PMID- 11252035
TI  - Mismatch between lactate and the apparent diffusion coefficient of water in
      progressive focal ischemia.
AB  - In this study, we examined mismatch in the area indicated by the normal apparent
      diffusion coefficient (ADC) of water and increased lactate in the early stage of
      focal cerebral ischemia. Five rats were subjected to permanent middle cerebral
      artery (MCA) occlusion. Diffusion-weighted echo planar imaging (DWEPI) and proton
      echo planar spectroscopic imaging (EPSI) were performed from 20 to 170 min after
      MCA occlusion, and lactate and N-acetyl asparate images were obtained by EPSI.
      Postmortem histological analysis was also performed. The areas of increased
      lactate and normal ADC were observed in the surrounding border zone of ischemia
      at approximately 20 min after MCA occlusion. This initial lactate in the border
      zone was significantly higher than that in the normal area, but lower than that
      in the ischemic core, which showed a reduction of ADC. However, this area was
      progressively involved in the ischemic core at 170 min without any treatment. The
      lactate-ADC mismatch in the initial period of ischemia may offer unique
      diagnostic information for ischemic tissue at high risk, followed by progressive
      involvement in the ischemic core without treatment. Considering that the
      accumulation of initial lactate in this area was not excessive, our findings may
      suggest that the lactate-ADC mismatch in the early period of ischemia indicates
      potentially salvageable tissue at high risk, requiring aggressive treatment.

PMID- 11252036
TI  - Alkaline pH changes in the cerebellum of asymptomatic HIV-infected individuals.
AB  - Human immunodeficiency virus (HIV) infection of the brain causes a complex
      cascade of cellular events involving several different cell types that eventually
      leads to neuronal cell death and the manifestation of the AIDS-associated
      dementia complex (ADC). Upon autopsy HIV-infected individuals show lesions within
      subcortical regions of the brain, including the cerebellum. Previously we have
      demonstrated, in primary and cell culture models of rat and human astrocytes, a
      change in intracellular pH (pH(i)) due to increased Na(+)/H(+) exchange following
      exposure to inactivated virus or gp120, the major HIV envelope glycoprotein. To
      further investigate whether any such in vivo pH(i) changes occur in human brains
      subsequent to HIV infection, we measured the pH(i) of the cerebellum in eight HIV
      positive individuals and nine healthy volunteers using (31)P magnetic resonance
      spectroscopy imaging (MRSI) at high field strength (4.1 T). The results showed a
      significant difference between the age-adjusted mean pH(i) in the cerebellum in
      control group and patient groups (7.11 +/- 0.03 vs 7.16 +/- 0.04), and further
      HIV-infected individuals displayed a significant increase in the number of
      cerebellar volume elements that were alkaline. We hypothesize that this
      propensity towards alterations in cerebellar pH(i) may portend later neurological
      involvement resulting from HIV infection.

PMID- 11252037
TI  - 1-(13)C glucose magnetic resonance spectroscopy of pediatric and adult brain
      disorders.
AB  - With protocols designed for use in a clinical environment we investigated the
      feasibility and diagnostic potential of (13)C MRS after 1-(13)C labeled glucose
      infusion. (13)C MRS brain examinations were performed in 27 subjects (17 children
      and pediatric patients, six adult patients, and four adult controls), using a
      standard 1.5 T clinical MR scanner. 1-(13)C glucose, 99% enriched (20% w/v) was
      administered intravenously (690 or 210 mg/kg body weight) or orally (730 mg/kg).
      Cerebral (13)C-enrichment patterns and time courses were compared. 1-(13)C
      glucose appeared in brain spectra within 2.5-15 min, with ensuing enrichment of
      its metabolites. No complications were encountered. When data obtained in
      patients were compared with controls, striking abnormalities in hepatic
      encephalopathy and in premature brain were observed, consistent with reduced
      cerebral glucose metabolism. Abnormalities in the (13)C enrichment pattern were
      also observed in pediatric patients with leukodystrophies and mitochondrial
      disorders. In this preliminary survey, we conclude that (13)C MRS in combination
      with glucose infusion is safe and efficient and provides new insights into the
      pathophysiology of brain disorders.

PMID- 11252038
TI  - Mobile lipid production after confluence and pH stress in perfused C6 cells.
AB  - NMR-visible mobile lipid (ML) has been observed in aggressive tumors and also in
      in vitro tumor cell models subjected to growth-inhibiting conditions, such as
      confluence or low-pH stress. The aim of the present study was to determine if ML
      production after confluence or low pH stress in a cultured cell model of brain
      tumor is due to growth arrest alone. ML was observed in situ by one- and two
      dimensional (1)H NMR in viable but growth-arrested C6 glioma cells superfused for
      a period of 48 h after harvesting. The rate of ML production in cells harvested
      at subconfluence was compared to the rate in cells confluent for one cell cycle
      and to the rate in subconfluent-harvested cells superfused at low pH (pH 6.1).
      Confluent-harvested cells produced ML at a markedly greater rate than that of
      cells harvested at subconfluence, suggesting the involvement of prior cell-cell
      contact rather than simple growth arrest. A high rate was also observed in
      subconfluent-harvested cells subjected to low pH, indicating that ML in pH
      stressed cells also does not arise from growth arrest alone. Furthermore, two
      dimensional data on the degree of unsaturation of the ML fatty acyl chains and
      one-dimensional (31)P and two-dimensional (1)H NMR data on the GPC content of the
      cells suggest distinct metabolic pathways for the production of ML following
      confluence and low-pH stress.

PMID- 11252039
TI  - A comparative fMRI study: T2*-weighted imaging versus R2* mapping.
AB  - Functional magnetic resonance imaging experiments were performed in human motor
      cortex at 1.5 T by sampling two successive gradient recalled echo images in a
      single shot. Several aspects of brain mapping methods based on T2*-weighted
      imaging and R2* mapping were quantitatively compared. These include the detected
      activation volume, functional contrast (FC), signal-to-noise ratio (SNR), and
      contrast-to-noise ratio (CNR). Studies based on the R2* mapping method have the
      following potential advantages: maximum functional contrast, less dependent on
      TE; and reduced inflow effects. R2* mapping produced the highest functional
      contrast, but not the largest activation volume due to the reduced signal-to
      noise ratio and inflow effects. The sensitivity for activation detection is
      significantly correlated with the contrast-to-noise ratio, which is determined by
      both the SNR and FC.

PMID- 11252040
TI  - Current awareness in NMR in biomedicine.
AB  - In order to keep subscribers up-to-date with the latest developments in their
      field, John Wiley & Sons are providing a current awareness service in each issue
      of the journal. The bibliography contains newly published material in the field
      of NMR in biomedicine. Each bibliography is divided into 9 sections: 1 Books,
      Reviews ' Symposia; 2 General; 3 Technology; 4 Brain and Nerves; 5
      Neuropathology; 6 Cancer; 7 Cardiac, Vascular and Respiratory Systems; 8 Liver,
      Kidney and Other Organs; 9 Muscle and Orthopaedic. Within each section, articles
      are listed in alphabetical order with respect to author. If, in the preceding
      period, no publications are located relevant to any one of these headings, that
      section will be omitted.

PMID- 11252041
TI  - Science or marketing at WHO? A commentary on 'World Health 2000'.

PMID- 11252042
TI  - Alternative approaches to obtain optimal bid values in contingent valuation
      studies and to model protest zeros. Estimating the determinants of individuals'
      willingness to pay for home care services in day case surgery.
AB  - The use of day case surgery has increased rapidly as an alternative to inpatient
      surgery. Little is known, however, about the value of day case surgery to
      patients. The aim of this paper was to develop a contingent valuation survey to
      investigate how individuals value the costs of shifting from inpatient to day
      case surgery based on home care services. Using the willingness to pay (WTP)
      approach, two kinds of sequential experiments are compared: the maximum
      likelihood recursion (MLR) method and the C-optimal sequential procedure. The
      goal of sequential experimentation is to find bid values that provide the maximum
      possible information about the parameters of the WTP distribution, especially
      when the sample size is small. The C-optimal sequential procedure is shown to be
      an improvement, in terms of the statistical precision in small samples, over the
      MLR method. In addition, the paper presents a double hurdle (DH) approach for
      modelling the determinants of individuals' WTP. Using data from a contingent
      valuation survey conducted in 1996 on patients selected from the Day Case Surgery
      Unit in a hospital in the region of Catalonia, we argue that participation in the
      market offered and the level of consumption, that is, people's WTP, should be
      treated as individual choices. The results show that income and sex are related
      to WTP. Also, in this study, a clear presence of starting-point bias, introduced
      by the bid offered, was found. It is concluded that the WTP technique is
      potentially useful in evaluating health care programmes, although it is important
      to note that the criteria used to find an optimal design (in our model to
      minimize the asymptotic variance of the estimator used) may be restrictive from
      an economic point of view.

PMID- 11252043
TI  - Strategic interaction among hospitals and nursing facilities: the efficiency
      effects of payment systems and vertical integration.
AB  - Rising post-acute care expenditures for Medicare transfer patients and increasing
      vertical integration between hospitals and nursing facilities raise questions
      about the links between payment system structure, the incentive for vertical
      integration and the impact on efficiency. In the United States, policy-makers are
      responding to these concerns by initiating prospective payments to nursing
      facilities, and are exploring the bundling of payments to hospitals. This paper
      develops a static profit-maximization model of the strategic interaction between
      the transferring hospital and a receiving nursing facility. This model suggests
      that the post-1984 system of prospective payment for hospital care, coupled with
      nursing facility payments that reimburse for services performed, induces
      inefficient under-provision of hospital services and encourages vertical
      integration. It further indicates that the extension of prospective payment to
      nursing facilities will not eliminate the incentive to vertically integrate, and
      will not result in efficient production unless such integration takes place.
      Bundling prospective payments for hospitals and nursing facilities will neither
      remove the incentive for vertical integration nor induce production efficiency
      without such vertical integration. However, bundled payment will induce efficient
      production, with or without vertical integration, if nursing facilities are
      reimbursed for services performed.

PMID- 11252044
TI  - Health insurance and health services utilization in Ireland.
AB  - The numbers buying private health insurance in Ireland have continued to grow,
      despite a broadening in entitlement to public care. About 40% of the population
      now have insurance, although everyone has entitlement to public hospital care. In
      this paper, we examine in detail the growth in insurance coverage and the factors
      underlying the demand for insurance. Attitudinal responses reveal the importance
      of perceptions about waiting times for public care, as well as some concerns
      about the quality of that care. Individual characteristics, such as education,
      age, gender, marital status, family composition and income all influence the
      probability of purchasing private insurance. We also examine the relationship
      between insurance and utilization of hospital in-patient services. The positive
      effect of private insurance appears less than that of entitlement to full free
      health care from the state, although the latter is means-tested, and may partly
      represent health status.

PMID- 11252045
TI  - Searching for a better willingness to pay elicitation method in rural Nigeria:
      the binary question with follow-up method versus the bidding game technique.
AB  - OBJECTIVES: To compare the theoretical validity and predictive validity of the
      binary with follow-up questions technique and the bidding game, using
      hypothetical and actual WTP for insecticide-treated nets (ITNs) in Nigeria.
      METHODS: Each elicitation method was applied in one of two rural communities in
      Enugu state, Nigeria. A pre-tested interviewer-administered questionnaire was
      administered to household heads or representatives of households. WTP was
      elicited in each after presenting the scenario and showing a sample of the ITNs
      to the respondents. Then, within an interval of 1-2 months, the nets were sold to
      the respondents to compare hypothetical and actual WTP. FINDINGS: Consistent
      slightly higher mean and median WTP amounts were elicited from Mbano where the
      bidding game was used. The WTP technique was able to predict WTP responses
      correctly in 75% and 85% of cases in Orba and Mbano, respectively. Chi-square
      analysis did not show any statistical difference in values from both communities
      (p>0.05). CONCLUSION: Though the two techniques yielded similar results, the
      thrust should be the development of a WTP elicitation method that best mimics the
      bargaining process in normal market situations in rural Nigeria. Such an
      indigenous technique will help improve the predictive validity of the contingent
      valuation method.

PMID- 11252046
TI  - Citizens, their agents and health care rationing: an exploratory study using
      qualitative methods.
AB  - This paper considers the application of the theoretical notion of a principal
      agent relationship to societal health care decision making. Current literature
      sheds little light upon whether a citizen-agent relationship exists in health
      care, with ambiguity about whether citizens want agents to make rationing
      decisions on their behalf, and if so, who these societal agents might be. A
      qualitative approach, using semi-structured interviews as the main instrument of
      data collection and analysis by constant comparison, was used to explore these
      issues with groups of both citizens and their potential agents. The findings of
      the research suggest that citizens vary considerably in the extent to which they
      want to be directly involved in making rationing decisions. Important influences
      on this issue appear to be knowledge and experience, objectivity and the
      potential distress that denying care may cause. Agents, in contrast, view
      citizens as needing agents to make decisions for them and suggest that it is
      primarily the health authority's role to act in this capacity. It is, however,
      apparent that the citizen-agent relationship in health care is both imperfect and
      complex, with final decisions resulting from the interaction between the utility
      functions of the various actors in the health care system. In practice a system
      of equivocation can be envisaged in which different groups collude as they
      attempt to avoid the disutility associated with denying care, with the
      consequence that the impact of decisions taken on an explicitly societal or
      citizen basis may be relatively small.

PMID- 11252047
TI  - Aging and health care expenditures: a comment on Zweifel, Felder and Meiers.

PMID- 11252048
TI  - The death of cost-minimization analysis?
AB  - Four different types of evaluation methods, cost-benefit analysis (CBA), cost
      utility analysis (CUA), cost-effectiveness analysis (CEA) and cost-minimization
      analysis (CMA), are usually distinguished. In this note, we pronounce the (near)
      death of CMA by showing the rare circumstances under which CMA is an appropriate
      method of analysis. We argue that it is inappropriate for separate and sequential
      hypothesis tests on differences in effects and costs to determine whether
      incremental cost-effectiveness (or cost-utility) should be estimated. We further
      argue that the analytic focus should be on the estimation of the joint density of
      cost and effect differences, the quantification of uncertainty surrounding the
      incremental cost-effectiveness ratio and the presentation of such data as cost
      effectiveness acceptability curves. Two examples from recently published CEA are
      employed to illustrate the issues. The first shows a situation where analysts
      might be tempted (inappropriately) to employ CMA rather than CEA. The second
      illustrates one of the rare circumstances in which CMA may be justified as a
      legitimate form of analysis.

PMID- 11252049
TI  - Deer mice: "The Drosophila of North American mammalogy".

PMID- 11252050
TI  - Larval development in Cnidaria: a connection to Bilateria?
AB  - Among the basal animal phyla, the Cnidaria display many characteristics similar
      to the Bilateria (the higher Metazoa). However, the relation of that outgroup
      phyla to the Bilateria is still equivocal. Additionally to morphological and
      genetic data, studies on cnidarian embryogenesis are essential to clarify the
      Cnidaria-Bilateria relationship. We analyzed cellular differentiation during
      planula larvae development of the jellyfish Podocoryne carnea. Within 24 to 30 h
      postfertilization, the diploblastic body structure and all cell types found in
      polyps have already differentiated in the larva. Whereas the differentiating
      smooth muscles, RFamide-positive nerve cells, or nematocytes (stinging cells)
      express no axial polarity, a newly discovered tyrosine-tubulin-positive nervous
      system develops gradually in repetitive patterns from anterior to posterior.
      These data demonstrate that part of the cnidarian nervous system develops from
      anterior to posterior in serially repeated patterns. This developmental mechanism
      seems to follow the bilaterian pattern and would have antedated the Cambrian
      explosion.

PMID- 11252051
TI  - Are we creating problems? Negative effects of Cre recombinase.

PMID- 11252052
TI  - Long-term, noninvasive imaging of regulated gene expression in living mice.
AB  - We describe here an approach for monitoring regulated gene expression by
      noninvasive imaging in living mice. We have utilized the tetracycline inducible
      system to simultaneously coregulate the expression of two genes encoding the
      firefly luciferase and the Cre recombinase, respectively. Results from our model
      system demonstrate that luciferase can be used as a noninvasive imaging marker
      for the regulated expression of a second gene in living mice. The integration of
      noninvasive imaging and inducible gene expression into current approaches of
      functional genomics should greatly advance our capabilities of carrying out
      highly controlled long-term studies of gene function in individual mice.

PMID- 11252053
TI  - The use of in ovo electroporation for the rapid analysis of neural-specific
      murine enhancers.
AB  - The identification and characterization of DNA sequences necessary for proper
      gene expression have provided insights into gene regulation and generated tools
      useful for further experimentation. Studies of developmentally regulated genes
      have demonstrated how transcription factors interact at enhancers to generate
      restricted patterns of expression during embryogenesis. In vertebrates, the
      pursuit of such studies has relied on the generation of transgenic mice and thus
      has been limited by the time and expense required generating and characterizing
      these mice. The recently developed technique of in ovo electroporation allows the
      rapid introduction of exogenous DNA into developing chicken embryos. Here we have
      used this technique to introduce DNA containing murine enhancer/reporter
      constructs into cells of the chicken neural tube, resulting in appropriate
      expression of the reporter. This technique has the potential to greatly reduce
      the effort involved in the study of vertebrate enhancers. Furthermore, we have
      characterized factors such as timing of electroporation, concentration of DNA,
      and choice of basal promoters and found that they can influence the degree to
      which expression of enhancer constructs reflects endogenous gene expression.

PMID- 11252054
TI  - An X-linked GFP transgene reveals unexpected paternal X-chromosome activity in
      trophoblastic giant cells of the mouse placenta.
AB  - A GFP transgene has been integrated on the proximal part of the mouse X
      chromosome just distal of Timp and Syn1. During development, this X-linked GFP
      transgene exhibits widespread green fluorescence throughout the embryonic and
      adult life of male mice but displays mosaic expression in tissues as a result of
      X-inactivation in females. In living female embryos, inactivation of the
      transgene is imprinted in extraembryonic regions and random in the embryo proper,
      demonstrating that this reporter is behaving in a similar fashion to the majority
      of X-linked loci, and so provides a vital readout of X chromosome activity. This
      is observation is further supported in T16H/X female mice harboring the GFP
      transgene on the normal X chromosome where reporter inactivation is observed in
      somatic cells. The differential expression of GFP activity facilitates
      fluorescence activated cell sorting for the purification of GFP+ vs. GFP- cells
      from female embryonic tissues, thereby allowing access to populations of cells
      that have kept active a particular X chromosome. By tracking the activity of this
      X-linked GFP transgene, we discovered that the primary and secondary giant cells
      of the X/X placenta maintain an active paternal copy of this transgene on the
      presumed silenced paternal X-chromosome. This finding implies that the imprint on
      the paternal X chromosome may be relaxed in these trophectodermal derivatives.

PMID- 11252055
TI  - Cortex, a Drosophila gene required to complete oocyte meiosis, is a member of the
      Cdc20/fizzy protein family.
AB  - Mutations in cortex and grauzone cause abnormal arrest in Drosophila female
      meiosis. cortex was mapped to a 14 kb interval in 26F-27A by the male
      recombination mapping method. While these experiments mapped the gene accurately,
      they also illustrated some complexities of this method. Rescue results showed
      that a 2.8 kb genomic fragment from this interval was able to fully rescue the
      cortex phenotype. The 2.8 kb rescuing fragment contains a single open reading
      frame. The predicted amino acid sequence indicates that cortex encodes a WD
      repeat protein and is a distant member of the Cdc20 protein family. Results from
      a developmental Northern analysis showed that the cortex transcript is expressed
      at high levels during oogenesis and early embryogenesis. Interestingly, the
      meiotic metaphase-anaphase II arrest defect in embryos laid by cortex homozygous
      females resembles the mitotic metaphase-anaphase defects observed in yeast cdc20
      mutants. The predicted nature of the Cortex protein, together with the observed
      meiotic phenotype in cortex mutants, suggest that a similar pathway to the cdc20
      dependent APC-mediated proteolysis pathway, which governs the metaphase-anaphase
      transition in mitosis, is also important in regulating oocyte meiosis.

PMID- 11252056
TI  - Syncope and neurologic deficits in a track athlete: a case report.
AB  - Exercise-related syncope may result from various underlying medical conditions,
      with vasovagal reactions being the most common cause in young athletes. However,
      psychological causes also need to be considered in the differential diagnosis of
      syncope. This case report presents an athlete who suffered a syncopal event with
      residual motor and sensory deficits. The athlete was diagnosed with a conversion
      disorder and was able to return to full competition following psychotherapy and
      physical therapy.

PMID- 11252057
TI  - Mucosal immunity, respiratory illness, and competitive performance in elite
      swimmers.
AB  - PURPOSE: Exercise and training are known to elicit changes in mucosal humoral
      immunity, but whether these alterations have any impact on competitive
      performance remains unclear. This investigation examined relationships between
      salivary immunoglobulin (Ig) concentration, the incidence of respiratory tract
      illness (RTI), and competitive performance in elite swimmers. METHODS: Forty-one
      members of the Australian Swimming Team (21 males and 20 females) aged 15-27 yr
      were monitored during preparations for the 1998 Commonwealth Games. Twenty-five
      coaches and staff (19 males and 6 females) aged 32-65 yr, serving as
      "environmental controls," were also monitored. Salivary IgA, IgM, and IgG and
      albumin concentration (mg.L-1) were measured in both groups in May 1998 and again
      in August 1998, 17 d before competition. Subjects were categorized as "ill" (at
      least one RTI) or "healthy". RESULTS: There were no significant changes in
      salivary IgA, IgM, or IgG concentration in the swimmers between May and August,
      nor were there any differences between healthy (N = 23) and ill (N = 18)
      swimmers. There was a significant positive relationship between IgM and
      performance in the male swimmers (r = 0.85, P < 0.001) but not for any other
      parameter. There was no significant difference in performance between ill and
      healthy swimmers (P = 0.11). Gold medal winners (N = 9) had higher IgM levels
      than other swimmers (N = 32) in May (P = 0.02) and higher IgG in August (P =
      0.02). CONCLUSION: These data indicate that a season of training by elite
      swimmers did not alter salivary immunoglobulin concentrations, and the presence
      of RTI had no significant impact on competitive performance.

PMID- 11252058
TI  - Stretching at the ankle joint: viscoelastic responses to holds and continuous
      passive motion.
AB  - PURPOSE: To compare the effect of static holds and continuous passive motion on
      stiffness and force relaxation of the soft tissue structures resisting ankle
      joint dorsiflexion. METHODS: This study used a randomized repeated measures trial
      design. Twenty-four asymptomatic subjects (15 males and 8 females) with a mean
      age of 26 yr participated. A Kin-Com dynamometer was used to measure the
      stiffness and force relaxation response of tissues about the ankle joint in
      response to a plantar flexor stretch. A comparison was made of the response for a
      1 x 60-s hold, 2 x 30-s holds, 4 x 15-s holds, and continuous passive motion for
      60 s. All subjects undertook all conditions. The main outcome measures were 1)
      stiffness at the ankle joint as it moved to 80% of the maximum range of
      dorsiflexion, and 2) the decrease in force at 80% of the maximum range of motion
      of the ankle joint. RESULTS: Stiffness was decreased significantly (P < 0.05) for
      the continuous passive motion condition only. The mean magnitude of the decrease
      in stiffness was 16%. Across hold times, force decreased significantly (P <
      0.05). Bonferonni contrasts indicated that there was a significant difference (P
      < 0.05) between the continuous passive motion condition and all other hold
      conditions. There were no significant differences (P > 0.05) between the 4 x 15
      s, 2 x 30-s, and 1 x 60-s holds. The magnitude of the decline in force was 10.5%,
      21.5%, 21.7%, and 19% for the 0-, 15-, 30-, and 60-s holds, respectively. The
      greatest decreases in tension were achieved in the first 20 s of a hold.
      CONCLUSION: If decreasing stiffness is a key aim of a stretching program, the
      findings indicate that continuous motion is more effective than holds. In
      contrast, if relaxation of peak tension is the main aim, then holds are most
      effective.

PMID- 11252059
TI  - 10-year trend in USA Cup soccer injuries: 1988-1997.
AB  - OBJECTIVE: To prospectively document the incidence of competition-related injury
      rates in an international youth soccer tournament and to analyze the type and
      location of injuries by age and gender. DESIGN: A prospective injury report form
      completed for injured players presenting to a medical facility for evaluation by
      the medical staff. SETTING: An international youth soccer tournament occurring
      annually during mid-July. PARTICIPANTS: 89,500 soccer players, ages 9-19.
      MEASUREMENT/MAIN RESULTS: A total of 3840 new, play-related injuries were
      evaluated during 290,344 player-hours of competition from 1988 through 1997. New,
      play-related injuries per 1000-player-hours decreased from 19.87 in 1988 to 9.89
      in 1997. Female injury rates ranged from a maximum of 20.11 in 1989 to a minimum
      of 10.23 in 1996 and the male injury rate ranged from a maximum of 20.04 in 1988
      to a minimum of 7.60 in 1996. The lowest injury rate occurred in the under-19
      females (10.64) and highest rates occurred in under-16 (17.68) and under-15
      (16.92) females. Heat illness correlated with mean temperature. The aggregate
      rate of heat illness was 0.6 cases/1000 player-hours under "normal" conditions
      compared to a rate of 2.8/1000 player-hours during "hot" years. CONCLUSIONS:
      Injury rates for both genders declined over the 10-yr span of the USA Cup study.
      The aggregate rate of injury was slightly higher for females than males although
      the difference between male and female rates became less significant as the
      tournament matured. In conditions of extreme heat and humidity (1988 and 1995)
      the rate of new, heat illness increased compared with normal years and females
      were 1.6 times more likely to sustain heat illness than males.

PMID- 11252060
TI  - Antioxidant and redox regulation of cellular signaling: introduction.
AB  - Oxidation-reduction (redox) based regulation of gene expression appears to be a
      fundamental regulatory mechanism in cell biology. This basic information has been
      exploited to develop novel strategies in clinical therapeutics. In contrast to
      the conventional idea that reactive species mostly serve as a trigger for
      oxidative damage of biological structures, we now know that low physiologically
      relevant concentration of reactive oxygen species can regulate a variety of key
      molecular mechanisms. Physical exercise causes redox changes in various cells and
      tissues. The molecular implications of such change are yet uncharacterized. The
      five component articles of this symposium discuss skeletal muscle contraction,
      cell adhesion, heat shock proteins, programmed cell death, and carbohydrate
      metabolism as they relate to physical exercise.

PMID- 11252062
TI  - Antioxidant regulation of cell adhesion.
AB  - Cell-cell and cell-matrix contacts are dependent on cell surface density,
      localization, and avidity state of surface-localized adhesion molecules. Cell
      adhesion represents a process that is centrally important in immune function and
      inflammation. This process is sensitive to various agonists including oxidants.
      Oxidants may directly as well as indirectly induce cell adhesion. In other cases,
      cytokines and related agents may induce cell adhesion by oxidant-dependent
      mechanisms. Various redox-sensitive sites in the signal transduction path leading
      to cell adhesion have been identified. Different chemical classes of nutritional
      antioxidants regulate cell adhesion by modulating specific signal transduction
      pathways. Numerous studies have confirmed that physical exercise influences the
      redox status of various cells and tissues. Recent evidences also show that
      physical exercise influences several cell adhesion related molecules. Whether
      such regulation has a redox component remains to be tested. Antioxidant
      supplementation studies testing the effect of exercise on cell adhesion should
      provide critical insight.

PMID- 11252061
TI  - Nitric oxide, reactive oxygen species, and skeletal muscle contraction.
AB  - Nitric oxide (NO) derivatives and reactive oxygen species (ROS) modulate
      contractile function of respiratory and limb skeletal muscle. The intracellular
      processes regulated by NO and ROS remain enigmatic, however. Studies of reduced
      preparations have identified a number of regulatory proteins that exhibit altered
      function when exposed to exogenous NO or ROS donors ex vivo. The relative
      importance of these targets in the intact cell is not known and conflicting
      theories abound regarding the mechanism(s) whereby NO and ROS regulate
      contraction. This review article provides a personal perspective on the processes
      regulated by NO and ROS by addressing three major topics: 1) the regulatory
      mechanisms by which endogenous NO depresses force production, 2) the processes
      whereby endogenous ROS modulate contraction of unfatigued muscle, and 3) the
      site(s) of action and reversibility of ROS effects in muscle fatigue.

PMID- 11252063
TI  - Redox regulation of skeletal muscle glucose transport.
AB  - Although the control of carbohydrate metabolism may be regulated by numerous
      factors, the redox state of the cell is of primary importance. The redox state
      may be influenced by a number of different factors, including different reactive
      oxygen species (ROS) and reactive nitrogen species (RNS) collectively, called
      reactive oxygen/nitrogen species (RONS). This review attempts to summarize the
      importance of redox regulation in relation to glucose transport and regulation of
      carbohydrate metabolism in skeletal muscle. In addition, prior studies
      implicating the role of different RONS in the control of glucose transport in
      skeletal muscle will be presented. Finally, the possible involvement of the cGMP,
      p21ras, and mean arterial pressure (MAP) kinase signal transduction cascades,
      which have been implicated with redox-sensitive alterations in glucose transport,
      will also be discussed.

PMID- 11252065
TI  - Apoptosis and exercise.
AB  - This brief review will discuss an exciting new area in exercise science, namely
      the role of apoptosis or programmed cell death in exercise. Apoptotic cell death
      differs morphologically and biochemically from necrotic cell death, although both
      appear to occur after exercise. Accelerated apoptosis has been documented to
      occur in a variety of disease states, such as AIDS and Alzheimer's disease, as
      well as in the aging heart. In striking contrast, failure to activate this
      genetically regulated cell death may result in cancer and certain viral
      infections. We will discuss factors that may activate apoptosis during and after
      exercise and the importance of cell turnover after exercise. We will also discuss
      differences in apoptosis between lymphocyte and skeletal muscle cells. We
      speculate that exercise-induced apoptosis is a normal regulatory process that
      serves to remove certain damaged cells without a pronounced inflammatory
      response, thus ensuring optimal body function.

PMID- 11252064
TI  - Exercise, heat shock proteins, and myocardial protection from I-R injury.
AB  - Heat shock proteins (HSPs) play a critical role in maintaining cellular
      homeostasis and protecting cells during episodes of acute stress. Specifically,
      HSPs of the 70 kDa family (i.e., HSP72) are important in preventing ischemia
      reperfusion induced apoptosis, necrosis, and oxidative injury in a variety of
      cell types including the cardiac myocyte. Evidence indicates that HSP72 may
      contribute to cellular protection against a variety of stresses by preventing
      protein aggregation, assisting in the refolding of damaged proteins, and
      chaperoning nascent polypeptides along ribosomes. Endurance exercise is a
      physiological stress that can be used to elevate myocardial levels of HSP72. It
      is now clear that endurance exercise training can elevate myocardial HSP72 by 400
      500% in young adult animals. Importantly, an exercise-induced elevation in
      myocardial HSPs is associated with a reduction in ischemia-reperfusion (I-R)
      injury in the heart. Although it seems likely that exercise-induced elevations in
      myocardial levels of HSPs play an important role in this protection against an I
      R insult, new evidence suggests that other factors may also be involved. This is
      an important area for future research.

PMID- 11252066
TI  - Differential effects of nandrolone decanoate in fast and slow rat skeletal
      muscles.
AB  - PURPOSE: We studied the effects of high doses of an anabolic-androgenic steroid,
      exercise training, and a combination of steroid and training on mammalian fast-
      and slow-twitch skeletal muscles at the cellular level. METHODS: Thirty-two male
      rats were divided into sedentary and treadmill-trained groups (increased speed
      and time: 18 m.min-1, 0.5 h.d-1, 5 d.wk-1). Eight animals of each group were
      treated with nandrolone decanoate (ND) (15 mg.kg-1.wk-1), and others received the
      same doses of solvent. The animals were killed after 5 wk, and the contractile
      parameters for isolated small bundles of soleus and extensor digitorum longus
      (edl) fibers were estimated. RESULTS: Muscle mass, twitches, and K+ contractures
      were increased in soleus and edl muscles after the drug treatment and after the
      exercise training. Caffeine contractures were increased only after the exercise
      training. The combination of exercise with ND treatment produced greater effects,
      particularly a significant increase in sensitivity to caffeine and the amplitude
      of K+ contractures as well as a shortening of the time required to restore
      contracture. These modifications were more marked in slow than fast muscle.
      CONCLUSION: These results show that 5 wk of exercise training produced changes in
      the contractile responses developed by isolated skeletal muscle cells. The
      combination of exercise training with ND treatment potentiated these effects,
      suggesting that there was some modification in the excitation-contraction
      coupling mechanism. ND treatment also produced a more potent effect in soleus
      than edl sedentary muscle.

PMID- 11252067
TI  - The influence of recovery posture on post-exercise hypotension in normotensive
      men.
AB  - PURPOSE: Postexercise hypotension may be the result of an impaired
      vasoconstrictor response. This hypothesis was investigated by examining the
      central and peripheral hemodynamic responses during supine and seated recovery
      after maximal upright exercise. METHODS: After supine or seated baseline
      measurements, seven normotensive male volunteers completed a graded upright
      cycling protocol to volitional exhaustion. This was immediately followed by
      either supine or seated recovery. Measurements of pulsatile arterial blood
      pressure and central and peripheral hemodynamic variables recorded 30 min before
      exercise were compared with those taken throughout 60 min of recovery. RESULTS:
      Compared with baseline, mean arterial pressure (MAP) was reduced after exercise
      (P < 0.05) although the degree of change was not different between the supine (-9
      +/- 4 mm Hg) and seated positions (-6 +/- 2 mm Hg). This change in MAP was
      associated with a reduction in diastolic blood pressure (DBP) (P < 0.05) and
      arterial pulse pressure (APP) (P < 0.01) for the supine and seated positions,
      respectively. The reduction in APP during seated recovery was accompanied by a
      decline in stroke volume (SV) (P < 0.05), not seen in the supine position, that
      limited the contribution of cardiac output (CO) to the maintenance of MAP. This
      effect of seated recovery was compensated by greater systemic (SVR) and regional
      vascular resistances in the forearm (FVR) and the forearm skin (SkVRA). There was
      also evidence of an augmented return of FVR and SkVRA to resting levels in the
      seated position after exercise. CONCLUSION: The lower peripheral resistance in
      the supine compared with seated recovery position suggests there is potential for
      greater vasoconstriction, although this is not evoked to increase blood pressure.
      This further suggests that the arterial baroreceptor reflex is reset to a lower
      operating pressure after exercise.

PMID- 11252068
TI  - Cardiorespiratory and metabolic characteristics of detraining in humans.
AB  - Detraining can be defined as the partial or complete loss of training-induced
      adaptations, in response to an insufficient training stimulus. Detraining is
      characterized, among other changes, by marked alterations in the
      cardiorespiratory system and the metabolic patterns during exercise. In highly
      trained athletes, insufficient training induces a rapid decline in VO2max, but it
      remains above control values. Exercise heart rate increases insufficiently to
      counterbalance the decreased stroke volume resulting from a rapid blood volume
      loss, and maximal cardiac output is thus reduced. Cardiac dimensions are also
      reduced, as well as ventilatory efficiency. Consequently, endurance performance
      is also markedly impaired. These changes are more moderate in recently trained
      subjects in the short-term, but recently acquired VO2max gains are completely
      lost after training stoppage periods longer than 4 wk. From a metabolic
      viewpoint, even short-term inactivity implies an increased reliance on
      carbohydrate metabolism during exercise, as shown by a higher exercise
      respiratory exchange ratio. This may result from a reduced insulin sensitivity
      and GLUT-4 transporter protein content, coupled with a lowered muscle lipoprotein
      lipase activity. These metabolic changes may take place within 10 d of training
      cessation. Resting muscle glycogen concentration returns to baseline within a few
      weeks without training, and trained athletes' lactate threshold is also lowered,
      but still remains above untrained values.

PMID- 11252069
TI  - Physiologic tolerance to uncompensable heat: intermittent exercise, field vs
      laboratory.
AB  - PURPOSE: This study determined whether exercise (30 min)-rest (10 min) cycles
      alter physiologic tolerance to uncompensable heat stress (UCHS) when outdoors in
      the desert. In addition, the relationship between core temperature and exhaustion
      from heat strain previously established in laboratory studies was compared with
      field studies. METHODS: Twelve men completed four trials: moderate intensity
      continuous exercise (MC), moderate intensity exercise with intermittent rest
      (MI), hard intensity continuous exercise (HC), and hard intensity exercise with
      intermittent rest (HI). UCHS was achieved by wearing protective clothing and
      exercising (estimated at 420 W or 610 W) outdoors in desert heat. RESULTS: Heat
      Stress Index values were 200%, 181%, 417%, and 283% for MC, MI, HC, and HI,
      respectively. Exhaustion from heat strain occurred in 36 of 48 trials. Core
      temperatures at exhaustion averaged 38.6 +/- 0.5 degrees, 38.9 +/- 0.6 degrees,
      38.9 +/- 0.7 degrees, and 39.0 +/- 0.7 degrees C for MC, MI, HC, and HI,
      respectively. Core temperature at exhaustion was not altered (P > 0.05) by
      exercise intensity or exercise-rest cycles and 50% of subjects incurred
      exhaustion at core temperature of 39.4 degrees C. These field data were compared
      with laboratory and field data collected over the past 35 years. Aggregate data
      for 747 laboratory and 131 field trials indicated that 50% of subjects incurred
      exhaustion at core temperatures of 38.6 degrees and 39.5 degrees C, respectively.
      When heat intolerant subjects (exhaustion < 38.3 degrees C core temperature) were
      removed from the analysis, subjects from laboratory studies (who underwent short
      term acclimation) still demonstrated less (0.8 degrees C) physiological tolerance
      than those from field studies (who underwent long-term acclimatization).
      CONCLUSION: Exercise-rest cycles did not alter physiologic tolerance to UCHS. In
      addition, subjects from field studies demonstrate greater physiologic tolerance
      than subjects from laboratory studies.

PMID- 11252070
TI  - Temperature responses to electrically induced cycling in spinal cord injured
      persons.
AB  - PURPOSE: The purpose of the study was to investigate the core temperature
      responses to the induction of electrical exercise and to clarify whether an
      increase in temperature could be responsible for some of the observed reactions
      to acute and repeated exposure to electrical muscle stimulation. METHODS: The
      paralyzed thigh and gluteal muscles were stimulated electrically with surface
      electrodes in seven persons with transection of the spinal cord. By this means,
      they were able to pedal a lower extremity ergometer at 50 revolutions per minute
      for 30 min. Skin surface, esophageal (Tes), rectal (Tre), and muscle temperature
      in m. quadriceps were measured with thermocouples. RESULTS: The average rate of
      oxygen consumption was 0.91 +/- 0.16 L.min-1, and the heart rate after 20 min was
      123 +/- 9 bpm during the electrically induced exercise. The involuntary, induced
      exercise led to increases in core temperature, whereas skin surface temperature
      was the same before and after exercise. Average Tes and Tre both rose 0.7 degrees
      C from, respectively, 36.6 +/- 0.2 and 36.9 +/- 0.1 degrees C, and muscle
      temperature increased even more: 2.9 degrees C from 33.9 +/- 0.3 degrees C.
      CONCLUSION: It is suggested that these increased temperatures may act as stimuli,
      directly or, through resulting release of humoral factors, and elicit the changes
      in heart rate, as well as the previously observed adaptive changes after
      electrically induced exercise, e.g., in muscle fiber size, and capillarization.

PMID- 11252071
TI  - Effect of eccentric exercise on muscle oxidative metabolism in humans.
AB  - PURPOSE: The purpose of this study was to evaluate the effects of eccentric
      exercise on muscle oxidative function. METHODS: Thirteen subjects performed high
      intensity eccentric cycling for 30 min. Muscle oxidative function in vastus
      lateralis was evaluated by measurements of respiration in permeabilized muscle
      fibers (skinned fibers) and from the kinetics of oxyhemoglobin (oxyHb) saturation
      measured with near infrared spectroscopy (NIRS). RESULTS: After eccentric
      cycling, all subjects reported extensive delayed onset muscle soreness (DOMS),
      but plasma markers of muscle damage (creatine kinase and beta-glucuronidase
      activity) were not significantly altered. The half time of oxyHb desaturation
      after circulatory occlusion (128 +/- 11 s, mean +/- SE) and oxyHb resaturation
      after restoration of blood flow (13.8 +/- 0.7 s) were not significantly changed
      after eccentric cycling (N = 7). Respiration in skinned muscle fibers measured in
      the absence of ADP and in the presence of a submaximal (0.1 mM) or maximal ADP
      concentration (1 mM) was not significantly changed after eccentric cycling (N =
      6). The sensitivity of respiration to ADP was not significantly changed after
      eccentric cycling. CONCLUSIONS: Muscle oxidative function (maximal respiration
      and respiratory control by ADP) was not compromised after high-intensity
      eccentric cycle exercise. Furthermore, NIRS indicates that after eccentric
      cycling muscle oxygen utilization and local oxygen transport at rest are
      unchanged. It is concluded that eccentric cycling, although causing DOMS, does
      not negatively affect skeletal muscle oxidative function.

PMID- 11252072
TI  - Muscle high-energy metabolites and metabolic capacity in patients with heart
      failure.
AB  - OKITA, K., K. YONEZAWA, H. NISHIJIMA, A. HANADA, T. NAGAI, T. MURAKAMI, and A.
      KITABATAKE. Muscle high-energy metabolites and metabolic capacity in patients
      with heart failure. Med Sci. Sports. Exerc., Vol. 33, No. 3, 2001, pp. 442-448.
      BACKGROUND: Various abnormalities in skeletal muscle have been demonstrated by
      biopsy in patients with chronic heart failure (CHF). In mammalian muscles, high
      energy metabolite composition at rest (HEMC) provides data on important metabolic
      characteristics; however, the significance of HEMC has not been clarified in
      patients with CHF. Therefore, we investigated HEMC in normal subjects and
      patients with CHF and examined its relation to muscle metabolic capacity and
      exercise tolerance. METHODS: High-energy metabolites (phosphocreatine (PCr),
      inorganic phosphate (Pi), and ATP) in resting calf muscle were measured by 31P
      magnetic resonance spectroscopy (31P-MRS), and ratios of Pi to PCr, Pi to ATP,
      and PCr to ATP were calculated in 34 patients with CHF and 13 age- and size
      matched normal subjects. Muscle metabolism was evaluated during local exercise of
      unilateral plantar flexion by 31P-MRS. Metabolic capacity was estimated by the
      rate of PCr breakdown in relation to the workload. Systemic exercise capacity was
      evaluated by a bicycle ergometer. RESULTS: The ratio of PCr to ATP was
      significantly increased in patients with CHF compared with controls (3.06 +/-
      0.43 vs 2.72 +/- 0.36, P < 0.05) and was significantly correlated with metabolic
      capacity (r = -0.37, P < 0.01) and with peak oxygen uptake (r = -0.45, P < 0.01).
      There was a significant correlation between metabolic capacity and peak oxygen
      uptake (r = 0.53, P < 0.001). CONCLUSION: HEMC was altered in patients with CHF,
      and this change was related to metabolic capacity and exercise capacity. These
      findings provide new insight into the mechanism of impaired muscle metabolism in
      CHF.

PMID- 11252074
TI  - Effects of an external nasal dilator on the work of breathing during exercise.
AB  - PURPOSE: The effect of an external nasal dilator on the work of breathing (WOB)
      was measured during exercise in 14 untrained college students (age, 23 +/- 2.7
      yr). METHODS: Two maximal, incremental ergometer tests were performed to
      exhaustion. Subjects wore a placebo or an active nasal dilator strip, in random
      order, during each test. An esophageal balloon was placed through each of the
      subject's mouth into the esophagus for measurement of inspiratory elastic work
      (INEW), inspiratory resistive work (INRW), and expiratory resistive work (EXRW).
      Subjects breathed through a Hans Rudolph(R) face mask that covered both the mouth
      and nose during both tests. Measured variables included oxygen uptake (VO2),
      ventilation (VE), tidal volume (VT), frequency of breathing (f), INEW, INRW, and
      EXRW (work expressed in joules). An alpha level was set at P < 0.05. RESULTS: No
      significant differences were found in INEW, INRW, and EXRW between conditions at
      70% of VO2max (mean +/- SD; Placebo: INEW, 25.6 +/- 17.8 J.min-1; INRW, 22.4 +/-
      15.8 J.min-1; EXRW, 16.7 +/- 12.3 J.min-1; Active: INEW, 24.7 +/- 12.9 J.min-1;
      INRW, 19.7 +/- 11.9 J.min-1; EXRW, 15.2 +/- 8.6 J.min-1; P > 0.05). No difference
      was found in INEW, INRW, and EXRW at maximal exercise between conditions (mean +/
      SD; Placebo: INEW, 50.2 +/- 29.9 J.min-1; INRW, 67.3 +/- 42.3 J.min-1; EXRW,
      102.3 +/- 78.4 J.min-1; Active: INEW, 45.7 +/- 19.6 J.min-1; INRW, 62.6 +/- 36.7
      J.min-1; EXRW, 86.3 +/- 50.9 J.min-1; P > 0.05). There were no differences in
      VO2, VE, VT, or f between conditions. CONCLUSION: Wearing an external nasal
      dilator does not significantly reduce the work of breathing during exercise.

PMID- 11252073
TI  - Short-term creatine supplementation does not alter the hormonal response to
      resistance training.
AB  - PURPOSE: In this study, the effect of short-term creatine supplementation on the
      growth hormone, testosterone, and cortisol response to heavy resistance training
      was investigated. METHODS: According to a double-blind crossover study design, 11
      healthy young male volunteers underwent a 1-h standardized heavy resistance
      training session (3 series of 10RM; 12 exercises), both before (pretest) and
      after (posttest) 5 d of either placebo (P, maltodextrine) or creatine (CR; 20 g.d
      1, 5 d) supplementation. A 5-wk washout period separated the treatments. Thirty
      minutes before each training session, CR subjects ingested 10 g of creatine
      monohydrate (CR) while P subjects received placebo. Venous blood was sampled
      before, immediately after, and 30 and 60 min after the training session. RESULTS:
      The exercise-induced increase (P < 0.05) of serum growth hormone was not altered
      by acute creatine intake and was similar in P and CR. The weight training
      session, either or not in conjunction with acute or chronic creatine intake, did
      not significantly impact on serum testosterone. However, serum cortisol during
      recovery tended to be higher in CR than in P. CONCLUSION: It is concluded that
      short-term creatine supplementation does not alter the responses of growth
      hormone, testosterone, and cortisol to a single bout of heavy resistance
      training.

PMID- 11252075
TI  - Nutrient intake of physically fit and unfit men and women.
AB  - OBJECTIVE: Participation in physical activity and following a diet low in fat,
      saturated fat, and cholesterol and high in fiber are important in the prevention
      and treatment of cardiovascular disease and other health problems. Despite the
      importance of both behaviors, little is known about the interactive role of diet
      and physical activity. The association between physical activity and diet has
      been studied, but data on the association between cardiorespiratory fitness
      (CRF), which is an objective measure of habitual physical activity, and diet are
      lacking in adults. This report examines nutrient intakes of men and women across
      low, moderate, and high fitness categories and compares the intakes to national
      dietary recommendations. It is the first step in examining the relationship
      between diet, CRF, and morbidity and mortality endpoints in the Aerobics Center
      Longitudinal Study (ACLS). METHODS: Between 1987 and 1995, 7959 men and 2453
      women participating in the ACLS provided 3-d diet records and completed a
      preventive medical examination. CRF was measured using a maximal exercise test,
      anthropometric and other clinical variables were measured following a
      standardized protocol, and lifestyle factors were assessed with a medical history
      questionnaire. RESULTS: After adjusting for potential confounders, there was a
      significantly lower percent of energy from fat and saturated fat across low,
      moderate, and high CRF categories. With additional adjustment for total energy
      intake, there was a significantly higher dietary fiber intake and a significantly
      lower cholesterol intake across CRF categories. The percentage of men and women
      meeting national dietary recommendations was higher at higher CRF levels.
      CONCLUSIONS: Men and women with higher fitness levels consumed diets that more
      closely approached national dietary recommendations than their lower fit peers.

PMID- 11252076
TI  - Validity of a physical activity questionnaire among African-American Seventh-day
      Adventists.
AB  - INTRODUCTION: Physical activity has been identified as an important predictor of
      chronic disease risk in numerous studies in which activity levels were measured
      by questionnaire. Although the validity of physical activity questionnaires has
      been documented in a number of studies of U.S. adults, few have included a
      validation analysis among blacks. We have examined the validity and reliability
      of a physical activity questionnaire that was administered to 165 black Seventh
      day Adventists from Southern California. METHODS: Subjects completed a self
      administered physical activity questionnaire and then "reference" measures of
      activity (7-d activity recalls, pedometer readings) and fitness (treadmill test)
      were completed in subsets of this population. RESULTS: The authors found that 7-d
      recall activity levels correlated well with the corresponding questionnaire
      indices among women (total activity, r = 0.65; vigorous, r = 0.85; moderate, r =
      0.44; inactivity, r = 0.59; sleep duration, r = 0.52) and men (total activity, r
      = 0.51; vigorous, r = 0.65; moderate, r = 0.53; inactivity, r = 0.69; sleep
      duration, r = 0.39). Vigorous activity from 7-d recalls was best measured by
      gender-specific indices that included only recreational activities among men and
      emphasized nonrecreational activities among women. Correlations between
      questionnaire data and the other "reference" measures were lower. Test-retest
      correlations of questionnaire items over a 6-wk interval were high (r = 0.4-0.9).
      CONCLUSION: Simple questions can measure activities of different intensity with
      good validity and reliability among black Adventist men and women.

PMID- 11252077
TI  - Biomechanical comparison of two racing wheelchair propulsion techniques.
AB  - PURPOSE: The purpose was to compare the conventional (CVT) and para-backhand
      (PBT) techniques used for racing wheelchair propulsion. Selected 3-D kinematic
      characteristics of the upper body and the electromyographic (EMG) signals of
      selected muscles during racing wheelchair propulsion over a roller system were
      examined. METHODS: Eight CVT and seven PBT elite performers served as the
      subjects. Each subject performed maximum effort pushing for 30 s at a load that
      simulated overground pushing. Two S-VHS camcorders (60 Hz) were used to obtain 3
      D kinematic parameters and muscle activity was monitored using surface
      electrodes. RESULTS: The CVT was found to have significant shorter push time,
      smaller relative push time, and greater relative recovery time than the PBT. The
      CVT is a more compact stroke (smaller joint range of motion) and the PBT has a
      faster overall movement speed. Significant differences in arm positions were
      found between the two techniques at the instants of hand contact and hand
      release, and the upper arm was more internally rotated at these two instants in
      the CVT when compared with the PBT. The EMG data showed that large variations in
      muscle activation patterns existed in each technique group. In general, the
      flexor carpi radialis and triceps brachii were most active in the push phase. The
      upper trapezius and postero-middle deltoids were most active in the ascending
      recovery phase, whereas the extensor carpi radialis, biceps brachii, antero
      middle deltoids, and pectoralis major were most active during the descending
      recovery phase. CONCLUSIONS: The greater push time and push angle associated with
      the PBT suggest that the PBT may be more suitable for endurance athletes who are
      less explosive in their pushing strokes. The greater time and angle allow PBT
      users the opportunity to transmit more force to the wheel.

PMID- 11252078
TI  - Effect of two drafting modalities in cycling on running performance.
AB  - PURPOSE: The purposes of this study were first to compare the physiological
      responses during a triathlon where cycling was performed alternatively with
      another cyclist (alternate draft triathlon, ADT) or continuously behind him
      (continuous draft triathlon, CDT), and second to study the incidence of these two
      drafting modalities in cycling on the subsequent running performance done during
      a simulated triathlon. METHODS: Ten male triathletes of national level performed
      a sprint distance triathlon (0.75-km swim, 20-km bike, 5-km run) on two different
      sessions, one where the triathlete alternatively rode in front or at the back of
      another cyclist and rotating every 500 m, the other where the triathlete drafted
      continuously a professional cyclist whose task was to reproduce all split times
      recorded during the alternate situation. Oxygen uptake (VO2), expiratory flow
      (VE), heart rate (HR) were recorded during the entire bike and run sections and
      blood lactate concentrations ([La-]b) were analyzed at the end of each event
      composing the triathlon. RESULTS: The results showed that expiratory flow, oxygen
      uptake, heart rate and blood lactate concentrations were significantly lower in
      CDT on the bike compared with drafting in alternation (148.1 vs. 167.2 L.min-1,
      49.9 vs. 59.8 mL.min-1.kg-1, 154.7 vs. 173.1 beats.min-1, 3.5 vs. 6.3 mmol.L-1,
      respectively). The results also revealed that running after biking in CDT (for
      similar cycling speeds) significantly improved the subsequent running speed
      compared to ADT (17.87 vs. 17.15 km.h-1). Furthermore, VE, VO2, HR, and [La-]b
      were significantly higher during CDT run compared with ADT run (175.6 vs. 170.4
      L.min-1, 69.7 vs. 66.8 mL.min-1.kg-1, 182.6 vs. 177.3 beats.min-1, 9.6 vs. 7.5
      mmol.L-1, respectively). CONCLUSIONS: These results showed that drafting
      continuously behind a lead cyclist allows triathletes to save a significant
      amount of energy during the bike leg of a sprint triathlon and creates the
      conditions for an improved running performance compared with a situation where
      cycling is performed alternating the lead with another cyclist.

PMID- 11252079
TI  - The effects of magnesium supplementation on exercise performance.
AB  - PURPOSE: To determine the effects of magnesium (Mg2+) supplementation on
      performance and recovery in physically active women using the sensitive and
      recently advanced measure of ionic Mg2+ (iMg). METHODS: Participants (N = 121)
      were screened for [iMg] in plasma, with 44 (36.4%) exhibiting [iMg] below the
      normal range of 0.53-0.67 mmol.L-1 (4). Thirty-two subjects (21 +/- 3 yr)
      representing a broad range of [iMg] (0.54 +/- 0.04 mmol.L-1) completed the main
      14-wk study. At baseline, participants submitted to a resting blood pressure
      measurement, and they completed both an anaerobic treadmill test and an
      incremental (aerobic) treadmill test. For the latter, values for workload, oxygen
      uptake, and heart rate were obtained at both anaerobic threshold and maximal
      effort. Blood samples for iMg, total serum Mg2+ (TMg), erythrocyte Mg2+ (EMg),
      Ca2+, K+, Na+, hemoglobin, hematocrit, lactate, and glucose were also collected
      pretest, and 4, 10, 30 min, and 24 h posttest. Subjects received 212 mg.d-1 Mg
      oxide or placebo in a double-blind fashion and were retested after 4 wk. After a
      6-wk washout period, the testing was repeated with a treatment crossover.
      RESULTS: Ionic Mg2+ increased with Mg2+ treatment versus placebo (P < 0.05);
      however, performance and recovery indices were not significantly affected.
      CONCLUSION: Four weeks of 212 mg.d-1 Mg oxide supplementation improves resting
      [iMg] levels but not performance or recovery in physically active women.

PMID- 11252080
TI  - Ice friction in speed skating: can klapskates reduce ice frictional loss?
AB  - PURPOSE: Reducing ice friction was one of the motives for developing the
      klapskate. However, the magnitude of power dissipation that occurs with
      conventional skates when a skater plantar flexes his ankle and the tip of the
      blade is pressed into the ice has not been quantified previously. In this study,
      we examine how ice friction varies during a single stroke with conventional
      skates and estimate the reduction in ice friction that might be obtained with
      klapskates. METHODS: Five elite speed skaters performed a series of trials at
      constant velocity and a series of maximal accelerations. Energy dissipated to ice
      friction during a stroke with conventional skates was analyzed using an
      instrumented skate and high-speed 3D kinematic analysis. The energy that would be
      dissipated when klapskates were used was estimated from the collected data with
      conventional skates. RESULTS: The estimated difference in power loss between
      conventional and klapskates was less dramatic than has been suggested frequently.
      Pressing the tip of the blade into the ice comprises only 0.84 W of the total
      power dissipated by ice friction (54 W) during constant velocity speed skating.
      During an all-out acceleration, this power loss reached 4.55 W. CONCLUSION: We
      conclude that only a minor part of the benefit of klapskates can be attributed to
      a reduction in ice friction. It is shown that this relatively small increase in
      ice friction is related to the large length of the skate blade.

PMID- 11252082
TI  - Conjunctival cul-de-sac reconstruction with radial forearm free flap in
      anophthalmic orbit syndrome.
AB  - Contracted eye socket is a constant cosmetic embarrassment to the patient. It not
      only renders patients unable to maintain an eye prosthesis, but it becomes a
      source of chronic discharge and irritation. Eye socket reconstruction with free
      skin, mucous membrane, cartilage, or dermis-fat usually remains unsatisfactory in
      many cases, due to secondary graft contracture. Traumatic injuries to the orbit
      and neighboring soft tissue frequently lead to a contracted eye socket. This
      condition results from the need for removal of the traumatized conjunctiva at the
      time of the enucleation, along with the traumatized eyeball, for satisfactory
      wound closure. In traumatic anophthalmos patients, a radial forearm free flap was
      used for conjunctival cul-de-sac reconstruction. Eye socket beds were developed
      as hinge-shaped flaps and used as lining for the upper and lower palpebrae. The
      authors conclude that the radial forearm flap is a useful alternative in the
      treatment of traumatic anophthalmos.

PMID- 11252081
TI  - Intraductal laser photocoagulation of the bilateral parotid ducts for reduction
      of drooling in patients with cerebral palsy.
AB  - Patients with cerebral palsy who experience drooling are often isolated from
      social interaction. Surgical treatment is effective in reducing abnormal, profuse
      drooling in patients who have low cognitive function, but it has a risk of
      complications. In this study, a new, simple procedure using laser intervention
      that minimizes surgical complications is described. Forty-eight patients with
      cerebral palsy and persistent drooling after more than 6 months of conservative
      treatment were enrolled in this study. An Nd:YAG laser (1064 nm) was used for
      intraductal laser photocoagulation of the bilateral parotid ducts at 7 to 10 W
      for 10 seconds. The outcome was evaluated by questionnaire-based,
      semiquantitative assessments of drooling severity and frequency, collection and
      measurement of stimulated saliva, and salivary amylase measurement. The entire
      procedure was completed in 25 to 65 minutes, with a mean duration of 38.4
      minutes. Early complications included transient facial swelling in all patients.
      Swelling persisted for 6 to 37 days (mean, 11 days). One hematoma (2.1 percent of
      patients), two infections (4.2 percent of patients), and two cystic formations
      (4.2 percent of patients) also occurred. No obvious xerostomia or visible scar
      was noted after the procedure. In the final assessment, a significant improvement
      in drooling severity (p < 0.05) and frequency (p < 0.05) was noted in the
      majority of cases. Forty patients (83.3 percent) demonstrated remarkable
      improvement in drooling severity, seven patients (14.6 percent) showed
      significant improvement, and one patient (2.1 percent), who was also autistic,
      continued to experience severe drooling after the laser procedure. The decrease
      in the amount of saliva produced ranged from 20 to 60 percent at 12 weeks after
      surgery. The decrease in the amount of salivary amylase measured ranged from 4 to
      97 percent at 12 weeks after surgery (p < 0.05). In conclusion, the intraductal
      laser photocoagulation of bilateral parotid ducts is a simple, effective
      procedure for reducing drooling in patients who have cerebral palsy. This
      procedure minimizes risks and complications, compared with those associated with
      conventional surgery.

PMID- 11252083
TI  - Direct local approach through a W-shaped incision in moderate or severe blowout
      fractures of the medial orbital wall.
AB  - For moderate or severe blowout fractures of the medial orbital wall, the goals of
      treatment are complete reduction of the herniated soft tissue and anatomic
      reconstruction of the wall without surgical complications. Various surgical
      approaches have been used, depending on the anatomic location and the extent of
      medial wall fracture. However, there is no consistent method to achieve the
      treatment goals with minimal morbidity because of one or more problems of
      limitation of entire medial wall exposure, limitation of large implant or bone
      graft insertion, surgical damage of important periorbital or intraorbital
      structures, or postoperative scar deformities. In this study, a direct local
      approach through a 3-cm, W-shaped incision on the superior medial orbital area
      was used as a consistent method to reconstruct medial orbital blowout fractures.
      The angle of the W-limbs is 110 to 120 degrees. Four limbs of the W were placed
      parallel or oblique to the relaxed skin tension lines. This technique was applied
      to 39 orbits of 37 patients with moderate or severe blowout fractures of the
      medial orbital wall. This approach provided exposure of the entire medial orbital
      wall, adequate placement of a large implant, short operation time within 2 hours,
      and no damage of important internal structures. Postoperative computed
      tomographic scans showed complete reduction of the herniated orbital tissues and
      anatomic reconstruction of the medial orbital wall without complication related
      to the surgical approach in all cases. During the follow-up period of 6 to 14
      months, excellent functional and cosmetic results were observed with an
      inconspicuous scar without secondary scar deformities. Therefore, a direct local
      approach through a W-shaped incision on the superior medial orbit may be a
      consistent method to gain the surgical goal in treatment of moderate or severe
      blowout fractures of the medial orbital wall.

PMID- 11252084
TI  - Temporoparietal-occipital flap for facial reconstruction.
AB  - Eight patients with an extensive facial defect of the masseter region were
      reconstructed with a temporoparietal- occipital rotation flap. This flap is
      vascularized by both the arteria auricularis posterior and the arteria
      occipitalis lateralis. These vessels have been sufficient to ensure viability of
      the entire flap. It is elevated and easily transposed to the masseter region
      because of the distensibility obtained from the posterior neck. This approach
      avoided the need for an unsightly skin graft at the site while providing tissue
      with hair follicles that blend well with the surrounding hair. This large flap
      offers cosmetic advantages over other techniques for coverage of facial defects
      in men.

PMID- 11252085
TI  - Giant congenital melanocytic nevi: the significance of neurocutaneous melanosis
      in neurologically asymptomatic children.
AB  - Patients with a giant congenital melanocytic nevus can develop melanotic tumors
      characterized by central nervous system involvement, termed leptomeningeal
      melanocytosis or neurocutaneous melanosis. Although symptomatic neurocutaneous
      melanosis is rare, we previously reported distinct magnetic resonance (MR)
      findings of T1 shortening, strongly suggestive of neurocutaneous melanosis, in 30
      percent (6 of 20) of children with giant congenital melanocytic nevi who
      presented initially without neurological symptoms. The purpose of this study was
      to determine the incidence of neurocutaneous melanosis in high-risk patients and
      its long-term clinical significance. Magnetic resonance imaging was recommended
      for all 46 patients with "at-risk" giant congenital melanocytic nevi involving
      the skin overlying the dorsal spine or scalp. The clinical histories and follow
      up of these patients were evaluated by retrospective chart review. Forty-two
      underwent MR imaging of the brain and 11 underwent additional MR scanning of the
      spinal cord. Abnormalities were identified in 14 of 43 MR studies, and 23 percent
      (n = 10) had T1 shortening indicative of melanotic rests within the brain or
      meninges. None had associated masses or leptomeningeal thickening. The most
      common areas of involvement in these 10 included the amygdala (n = 8), cerebellum
      (n = 5), and pons (n = 3). In the group of 11 patients with spinal MR scans, a
      tethered spinal cord was demonstrated in one. Additional abnormalities were
      detected by MR scanning, including a middle cranial fossa arachnoid cyst, a
      Chiari type I malformation, and a crescentic enhancement that subsequently
      resolved. Clinical follow-up averaging 5 years (range, 2 to 8 years) revealed
      that only one of the 46 patients evaluated developed neurological symptoms,
      manifested as developmental delay, hypotonia, and questionable seizures but no
      other signs of neurocutaneous melanosis. No patient has developed a cutaneous or
      central nervous system melanoma. Magnetic resonance findings of neurocutaneous
      melanosis are relatively common, even in asymptomatic children with giant
      congenital melanocytic nevi. Although these findings suggest an increased
      lifetime risk of central nervous system melanoma, they do not signify the
      eventual development of symptomatic neurocutaneous melanosis during childhood.

PMID- 11252087
TI  - Gynecomastia and the complete circumareolar approach in the surgical management
      of skin redundancy.
AB  - Gynecomastia is a benign enlargement of the male breast due to a physiological or
      pathological factor that interferes with the balance between estrogens and
      androgens in the serum. Gynecomastia itself requires no treatment unless the
      persistent enlargement of the male breast is a source of embarrassment and/or
      distress for the adolescent or adult man. The indications for the surgical
      treatment of gynecomastia are founded on two main objectives: (1) the restoration
      of male chest shape and (2) diagnostic evaluation of suspected breast lesions.
      The diagnostic evaluation begins with an adequate history and a thorough breast
      examination helped by laboratory tests and instrumental research. Several
      approaches for surgical treatment have been described in the literature. Some
      problems arise in patients who have significant enlargement and ptosis of the
      breast that will require skin reduction and in some patients requiring nipple
      areola complex reduction. The authors believe that the complete circumareolar
      technique with purse-string suture creates the best aesthetic results, with fewer
      complications, in patients with moderate and severe ptotic glandular breast
      enlargements that have skin redundancy combined with areolar enlargement. From
      1995 through 1999, a total of 10 male patients with moderate to severe
      gynecomastia were treated surgically using a complete circumareolar approach. All
      patients achieved a good aesthetic contour of the chest. Only two patients
      required a revision of the circumareolar scar to correct postoperative
      enlargement.

PMID- 11252086
TI  - A prospective study of the accuracy of the surgeon's diagnosis and significance
      of positive margins in nonmelanoma skin cancers.
AB  - Even with a precise preoperative diagnosis, complete excision of nonmelanoma skin
      cancer is not always achieved. The conundrum remains the decision for appropriate
      secondary treatment. Many surgeons, regardless of the nature of the lesion,
      consider re-excision to be the only option. In a prior 4-year prospective study
      that ascertained the accuracy of our clinical diagnosis of skin lesions removed
      in an office setting, one-fifth were found to be malignant and 98 percent (n =
      415) of the lesions were nonmelanoma skin cancer. Unfortunately, 65 (15.7
      percent) of the malignant nonmelanoma skin cancer lesions had positive margins.
      The outcome of our management for these specific lesions was followed
      prospectively over the 7.5 years of this study to determine whether aggressive
      surgical intervention was justified in every case. Of 65 patients with lesions,
      early and complete re-excision of margin-positive nonmelanoma skin cancer was
      performed for 34 (52.3 percent), with residual tumor found in 11 (32.4 percent),
      followed by a later recurrence in one (2.9 percent). The remaining 31 patients
      agreed to semiannual office visits, with one (3.2 percent) recurrence in this
      group. Thus, the overall rate of recurrence for margin-positive nonmelanoma skin
      cancer was 3.1 percent, with a mean follow-up of 3.6 years (range, 0 to 7.5
      years). There were no recurrences for basal cell carcinoma in either treatment
      group, suggesting that, at least for "simple" primary lesions without confounding
      risk factors, there is some validity to a "wait and see" attitude, in which
      treatment of a potential recurrence would be straightforward. Despite our
      observed infrequent local recurrences of squamous cell cancers (13.3 percent),
      the small risk of metastases still suggests the appropriateness of complete
      surgical eradication for these tumors whenever feasible.

PMID- 11252088
TI  - Maximizing breast projection after free-nipple-graft reduction mammaplasty.
AB  - In 1922, Thorek described standard free-nipple reduction mammaplasty for
      gigantomastia. This technique provided a simple and effective way to perform
      reduction mammaplasty. However, the technique is frequently criticized for
      producing a breast and nipple with poor projection. Even with the standard
      modification of the original technique, the resultant breast and nipple may be
      wide and flat, with unpredictable nipple-areola pigmentation. To create a breast
      mound and nipple with projection and even pigmentation, the free-nipple-graft
      breast reduction technique is presented. The Wise pattern skin reduction markings
      and the superiorly based parenchymal reduction technique are used. After the
      nipple-areola complex is removed, as a free graft, the inferior pole of the
      breast is then amputated along the Wise pattern skin markings, leaving lateral
      and medial pillars of breast tissue, with the apex of the resection corresponding
      to the new nipple location. The lateral and medial pillars of the superiorly
      based breast mound are then sutured together. Key interrupted sutures are placed,
      beginning at the most inferior and posterior point of the pillars, while
      recruiting tissue centrally to increase the projection. The intersecting point of
      the inverted T, at 7 cm from the new nipple position, is then sutured to the
      fasciae of the pectoralis major muscle. If more central projection is desired,
      the vertical limb design can be lengthened. The tissue inferior to the 7-cm mark
      is de-epithelialized and tucked under the central breast, if needed, contributing
      further to the final breast parenchyma projection. The skin of the vertical limb
      of the Wise pattern is then closed with a dog-ear at the apex to further
      contribute to nipple projection. The nipple is replaced as a free, thick, split
      thickness skin graft. The breast is temporarily closed, and the medial and
      lateral breast tissue excess is liposuctioned to create a more conical breast.
      Excessive medial and lateral skin is then resected, keeping the inframammary
      crease incision under the breast mound. Twenty-five patients underwent free
      nipple-graft reduction mammaplasty using this technique between 1992 and 2000. An
      average of 1600 g of breast tissue per breast was removed. The average follow-up
      period was 36 months. Patient satisfaction has been very high.

PMID- 11252089
TI  - Maximizing breast projection after free-nipple-graft reduction mammaplasty.

PMID- 11252090
TI  - Short-scar breast reduction: why all the fuss?
AB  - The breast can be considered conceptually as a cone. This article compares and
      contrasts short-scar breast reduction techniques with inverted T techniques using
      the cone model. Four issues are examined-the base of the breast, breast
      projection, the inframammary fold, and the pedicle. The short-scar techniques
      focus on reshaping the breast parenchyma, and skin redraping occurs secondarily.
      Application of this model suggests that these techniques have the advantage of
      better projection and greater longevity. These techniques seldom give a square
      shape and are better at dealing with upper pole deficiency. However, the ability
      of the skin to redrape is the limiting factor; hence, results are less
      predictable with large-volume breast reductions. The emphasis of this article is
      on increasing the understanding of the mechanics of breast reduction. It is this
      factor that will enable appropriate selection of a particular technique.

PMID- 11252091
TI  - Breast sensitivity after vertical mammaplasty.
AB  - Breast sensation after reduction mammaplasty is a major concern for surgeons and
      patients. The sensitivity of 80 breasts that were reduced using Lejour's
      technique (a superior dermoglandular pedicle with resection at the lower
      quadrants) was assessed in a prospective study. Ten points were selected on each
      breast for this study, including the nipple, four points on the areola, and five
      points on the breast skin. The measurements were performed preoperatively and at
      3, 6, and 12 months postoperatively. Pressure thresholds were measured with 20
      Semmes-Weinstein monofilaments, temperature sensitivity with hot and cold metal
      probes, vibratory thresholds with the Biotesiometer, and static and moving two
      point discrimination tests with a Disk-Criminator. To assess the influence of
      breast ptosis and hypertrophy on sensitivity, the population was divided into two
      groups. In group I (19 patients), the sternal notch-to-nipple distance was less
      than 29 cm, and less than 500 g of tissue per breast was removed. In group II (21
      patients), the sternal notch-to-nipple distance was more than 29 cm, and more
      than 500 g of tissue was resected. The sensitivity on the nipple and areola was
      significantly decreased at 3 and 6 months postoperatively for all modalities. At
      1 year, sensitivity recovered, and no breast or nipple-areola complex was
      insensitive. Pressure sensitivity was not significantly different from the
      preoperative measurement in any area of the breast or in either group of
      patients, except for superior breast skin, for which sensitivity was improved in
      group II (p = 0.0004). Temperature sensitivity in group I was not different
      preoperatively and postoperatively, but in group II, a significant decrease was
      observed in sensitivity for the nipple and areola (p = 0.01 and 0.004,
      respectively). Vibratory sensitivity was significantly decreased on the nipple,
      the areola, and the inferior breast skin (p = 0.01, 0.01, and 0.001,
      respectively) in group II but not in group I. In conclusion, ptotic or moderately
      hypertrophied breasts that were reduced using Lejour's technique recovered their
      preoperative level of sensitivity after an initial postoperative decline.
      However, in large breasts, although pressure sensitivity recovered after 1 year,
      temperature and vibration sensitivity remained diminished on the nipple-areola
      complex.

PMID- 11252092
TI  - Induction of bone formation by recombinant human osteogenic protein-1 and
      sintered porous hydroxyapatite in adult primates.
AB  - A critical issue in tissue engineering and morphogenesis of bone is the
      development of novel biomimetic biomaterials that are capable of optimizing the
      biological activity of recombinant human bone morphogenetic and osteogenic
      proteins, which are molecules that initiate bone formation in vivo. From a
      therapeutic perspective, a carrier matrix is required for the local delivery of
      these proteins to evoke a desired osteogenic effect. In view of the affinity of
      these proteins for hydroxyapatite, which may reflect the in vivo supramolecular
      assembly of bone proteins bound to both the extracellular matrix and the mineral
      component of bone, we investigated the efficacy of single applications of
      different doses of human osteogenic protein-1 (hOP-1) adsorbed onto sintered
      porous hydroxyapatites for bone induction in orthotopic calvarial defects in 12
      adult male baboons (Papio ursinus) and heterotopically in the rectus abdominis of
      four additional baboons. In orthotopic specimens, pretreatment of sintered porous
      hydroxyapatites with 100 microgram of hOP-1 in 500 microliter of 5 mM
      hydrochloric acid resulted in rapid and diffuse osteoinduction restricted within
      the porous spaces of the hydroxyapatite, as evaluated by histology and
      histomorphometry on day 30. Hydroxyapatites treated with 500 microgram of hOP-1
      showed a different pattern of bone formation and distribution on day 30 as
      compared with the lower dose of the recombinant morphogen. Although bone
      formation was extensive with the higher dose, it was found on the endocranial and
      pericranial aspects of the specimens, enveloping the implanted hydroxyapatite
      carrier, and the internal porous spaces were occupied by a rich vascular network
      without any bone formation. By 90 and 365 days after the implantation of both
      doses of hOP-1, however, there was remodelling and complete penetration of the
      newly induced bone within the available porous spaces. The combination of hOP-1
      and hydroxyapatite also showed extensive bone formation in heterotopic specimens
      harvested from the rectus abdominis muscle of the baboon using doses of 5, 25,
      and 45 microgram of hOP-1 per implant. These findings in the adult primate
      demonstrate extensive bone formation by hOP-1 adsorbed onto sintered porous
      hydroxyapatites and suggest that predictable osteogenesis in clinical contexts
      for treatment of craniofacial bone defects may be engineered using inorganic,
      nonimmunogenic, and carvable delivery systems that initiate osteogenesis with
      relatively low doses of recombinant osteogenic proteins, thus mimicking the
      macrostructure and microstructure of living bone.

PMID- 11252093
TI  - Recombinant human acidic fibroblast growth factor and fibrin carrier regenerates
      bone.
AB  - Bone regeneration promoted by acidic recombinant human fibroblast growth factor
      (rhFGF-1), rabbit demineralized bone matrix (rDBM), and a fibrin (f) delivery
      system was measured in critical-sized defects in rabbits' radii. A unilateral
      segmental defect 20 mm in length was prepared in radii of 48 skeletally mature
      New Zealand White rabbits divided equally between 4- and 8-week cohorts. The
      temporal cohorts were divided equally among four treatment groups: rDBM, rDBM/f,
      rDBM/rhFGF-1/f, and rhFGF-1/f. Data for the fifth group, untreated critical-sized
      defects, were exploited from previous published reports from this laboratory. In
      response to experimental treatments, radiomorphometric and histomorphometric
      methods were used to derive quantitative outcome data that were tested by
      analysis of variance and post hoc multiple comparison tests (significance p </=
      0.05). Radiomorphometric data (percentage of radiopacity of defect) were acquired
      at the day of the operation and every 2 weeks thereafter, whereas
      histomorphometric data (square millimeters of new bone formation) were determined
      at term. The objective for the study was to develop candidate bone regenerative
      therapies. Therefore, the hypotheses were that experimental treatments would
      promote bone formation within critical-sized defects and that one treatment would
      be superior to the rest. Testing hypotheses was achieved with quantitative
      methodology, and data were subjected to statistical models. Radiopacity at each 2
      week period was greater in treated defects than in untreated critical-sized
      defects. The amount of radiopacity promoted by rDBM/f and rhFGF-1/f at 8 weeks
      was equivalent and was greater than antecedent times. Histomorphometric data
      analyses indicated that rDBM/f and rDBM evoked the same quantity of new bone
      formation at 4 weeks; by 8 weeks, all treatments except rDBM/f had more new bone
      within the critical-sized defects in comparison to untreated defects. That rDBM/f
      promoted less new bone than rDBM alone may suggest fibrin decreases bone
      formation, perhaps by impeding local solubility of endogenous and rDBM-containing
      signaling molecules. However, rhFGF-1/f promoted a significant and unexpected
      increase in bone formation response that could refute the previous notion. In
      conclusion, the combination of rDBM/rhFGF-1/f may represent a significant, new
      osteogenic therapeutic regimen. Additional assessments in higher order species
      must be accomplished to corroborate efficacy.

PMID- 11252094
TI  - Immediate pectoralis flap closure following septic arthritis of the
      manubriosternal joint.

PMID- 11252095
TI  - Ectopic implantation of constriction band intrauterine digital amputation.

PMID- 11252097
TI  - Delayed full-thickness autografting of cryopreserved avulsed skin in degloving
      injuries of the extremities.

PMID- 11252096
TI  - Endoscopic harvest of free temporoparietal fascial flap to improve donor-site
      morbidity.

PMID- 11252098
TI  - The plastic surgeon of the 20th century.

PMID- 11252099
TI  - Massive infectious soft-tissue injury: diagnosis and management of necrotizing
      fasciitis and purpura fulminans.
AB  - LEARNING OBJECTIVES: After studying the article, the participant should be able
      to: 1. Describe the most common bacteriology of necrotizing fasciitis and purpura
      fulminans. 2. Describe the "finger test" in the diagnosis of necrotizing
      fasciitis. 3. Discuss the three presentation patterns of necrotizing fasciitis.
      4. Discuss the pathophysiology of acute infectious purpura fulminans. 5. Discuss
      the treatment strategies for necrotizing fasciitis and purpura fulminans,
      including the use of artificial skin substitutes. Necrotizing fasciitis and
      purpura fulminans are two destructive processes that involve skin and soft
      tissues. The plastic and reconstructive surgeon may frequently be called on for
      assistance in the diagnosis, treatment, and/or reconstruction of patients with
      these conditions. Understanding the natural history and unique characteristics of
      these processes is essential for effective surgical management and favorable
      patient outcome. A comprehensive review of the literature pertaining to these two
      conditions is presented, outlining the different pathophysiologies, the patterns
      of presentation, and the treatment strategies necessary for successful management
      of these massive infectious soft-tissue diseases.

PMID- 11252100
TI  - Why i hate the headlight. and other ways to protect your cervical spine.

PMID- 11252101
TI  - Perioperative management of cosmetic liposuction.
AB  - Recent qualms about the safety of aesthetic lipoplasty may be attributable more
      to support system flaws than to technical process deficiencies. The authors here
      focus on perfunctory patient monitoring when sedative or analgesic drugs are
      given, cavalier infiltration of mega-dose lidocaine, cursory intraoperative
      patient observation by team members with conflicting responsibilities, anesthesia
      providers unfamiliar with the unique surgical physiology of liposuction, hurried
      discharge policies that virtually ignore the residual depressant effects of
      sedatives and analgesics, and compressive dressings that impair postoperative
      chest-wall expansion and venous return. Whereas pulmonary embolism remains the
      leading process cause of morbidity from liposuction, complications from austere
      resource allocation to dedicated patient monitoring should be largely
      preventable. Not all lipoplasties require an anesthesia provider but-when heavy
      sedation, mega-dose lidocaine, or both, are projected-a trained team member
      dedicated exclusively to patient safety and comfort should be a minimum patient
      care standard. The potential role of lidocaine cardiotoxicity in tumescent
      anesthesia is widely underappreciated and that of hypothermia goes mostly
      unrecognized. These, plus largely preventable or potentially correctable
      perioperative events such as pulmonary edema, fluid imbalance, or improperly
      administered sedative and analgesic drugs, demand upgrading and expansion of
      monitoring, resuscitative, and recuperative facilities in physician offices. In
      fact, ASPS guidelines urge that anesthesia services be engaged for dedicated
      patient care whenever "major" liposuction or conscious sedation is projected,
      because liposuction is neither as benign nor as simple a procedure as heretofore
      reputed. To assess objectively the operative and anesthetic risk of obesity,
      document body mass index for the preoperative record; morbid obesity (body mass
      index >/= 35.0), for instance, is a known risk multiplier for sedatives and
      analgesics. Other system issues such as the dynamic profile of high-dose
      lidocaine pharmacokinetics, the deportation of fat globules in the bloodstream,
      and the incidence of intraoperative hypothermia remain as unresolved topics for
      interdisciplinary, multi-institutional clinical research.

PMID- 11252102
TI  - Subperiosteal and full-thickness skin rhytidectomy.
AB  - Subperiosteal lateral brow and midface elevation, upper lid blepharoplasty,
      transconjunctival retroseptal fat removal, lower lid skin excision, and full
      thickness skin rhytidectomy are combined in one operation to rejuvenate the
      entire face. This combination of procedures is designed to restore both
      anthropometric and subjective attributes of youth. The attributes of a youthful
      face may be summarized as brows with an apex lateral slant, eyes that are narrow,
      lower lids that are short, cheeks that are full, and necks that are well defined.
      In addition to restoring a youthful appearance, the techniques described avoid
      some common iatrogenic sequelae of facial rejuvenative surgery. In a clinical
      experience with 28 patients over 3 years, this combination of procedures has
      proved to be safe and predictable.

PMID- 11252103
TI  - Improved technique for fascial sling reconstruction of severe congenital ptosis.

PMID- 11252104
TI  - Composite tissue (hand) allotransplantation: are we ready?

PMID- 11252105
TI  - Composite tissue transplantation: more science and patience needed.

PMID- 11252106
TI  - Modification of the Skoog principle of digital flap interposition with a new
      technique of web space reconstruction.

PMID- 11252107
TI  - Salt and hypertension: going to the heart of the matter.

PMID- 11252108
TI  - Salt and hypertension: the debate that begs the bigger question.

PMID- 11252109
TI  - Should new drugs be used without outcome data? Implications of Allhat and Elite
      II.

PMID- 11252110
TI  - Cardiovascular disease and dyslipidemia in women.
AB  - Cardiovascular disease, primarily coronary heart disease (CHD), outnumbers the
      next 16 causes of death in women combined. However, the long-held belief that
      heart disease in women has a more benign prognosis than in men has resulted in
      less aggressive diagnosis and management patterns. Appreciation of the
      differences between men and women in CHD risk factors and presentation can assist
      in treatment decisions. Although estrogen replacement offers substantial
      beneficial effects on lipid levels in postmenopausal women, the first 2
      randomized trials of estrogen alone and estrogen plus progestin, the Heart and
      Estrogen/Progestin Replacement Study and Estrogen Replacement and Atherosclerosis
      Study, observed no benefit in reducing risk of CHD death and nonfatal myocardial
      infarction and angiographic progression of CHD, respectively, in women with CHD.
      Available data show that lipid-lowering therapy reduces women's CHD risk and
      mortality but also indicate that a considerable proportion of women remains
      untreated or undertreated. Randomized trials of statins for primary and secondary
      prevention of coronary heart disease suggest that these agents are at least as
      effective for lowering coronary disease risk in women as in men. Therefore,
      statin drugs should be the drug of first choice for women with established CHD.
      Hypercholesterolemic postmenopausal women who require estrogen for menopausal
      symptoms may derive further reductions in low-density lipoprotein cholesterol and
      reductions in trigyceride levels with the addition of a statin drug.

PMID- 11252111
TI  - Clostridium difficile--Associated diarrhea: A review.
AB  - Clostridium difficile causes 300 000 to 3 000 000 cases of diarrhea and colitis
      in the United States every year. Antibiotics most frequently associated with the
      infection are clindamycin, ampicillin, amoxicillin, and cephalosporins, but all
      antibiotics may predispose patients to C difficile infection. The clinical
      presentation varies from asymptomatic colonization to mild diarrhea to severe
      debilitating disease, with high fever, severe abdominal pain, paralytic ileus,
      colonic dilation (or megacolon), or even perforation. The most sensitive and
      specific test available for diagnosis of C difficile infection is a tissue
      culture assay for the cytotoxicity of toxin B. However, this test takes 1 to 3
      days to complete and requires tissue culture facilities. Detection of C difficile
      toxin by means of enzyme-linked immunoassay is more rapid and inexpensive. A
      minority of patients may require more than 1 stool assay to detect toxin. Oral
      metronidazole or oral vancomycin hydrochloride for 10 to 14 days are equally
      effective at resolving clinical symptoms; oral metronidazole is preferred in most
      cases because of lowered cost and less selective pressure for vancomycin
      resistant organisms. Approximately 15% of patients experience relapse after
      initial therapy and require retreatment, sometimes with an extended, tapering
      regimen. Immunity appears to be incomplete and predominantly mediated by serum
      IgG to toxin A. Measures for preventing the spread of the pathogen, appropriate
      diagnostic testing, and treatment may avert morbidity and mortality due to C
      difficile-associated diarrhea.

PMID- 11252112
TI  - Aspirin and angiotensin-converting enzyme inhibitors among elderly survivors of
      hospitalization for an acute myocardial infarction.
AB  - BACKGROUND: Aspirin and angiotensin-converting enzyme (ACE) inhibitors are
      recommended for secondary prevention after acute myocardial infarction (AMI), but
      several studies have suggested that the combination of these medications may
      produce a negative interaction. OBJECTIVE: To evaluate the effect and interaction
      of aspirin and ACE inhibitors on mortality among elderly patients who survived a
      hospitalization for AMI. METHODS: We evaluated the effect and interaction of
      aspirin and ACE inhibitors on mortality in patients aged 65 years and older who
      survived hospitalization with a confirmed AMI who were ideal candidates for the
      therapies. RESULTS: Among the 14 129 patients, 26% received aspirin only, 20%
      received ACE inhibitors only, 38% received both, and 16% received neither at
      discharge. In the multivariate analysis, patients who received both aspirin and
      ACE inhibitors alone had a significantly lower 1-year mortality (adjusted risk
      ratio [ARR], 0.86 [95% confidence interval (CI), 0.78-0.95] vs 0.85 [95% CI, 0.77
      0.93], respectively) compared with patients who received neither aspirin nor ACE
      inhibitors at discharge. Prescribing both aspirin and ACE inhibitors was
      associated with a slightly lower risk of mortality (ARR, 0.81; 95% CI, 0.74-0.88)
      than that seen in aspirin-only or ACE inhibitor-only groups, but the difference
      was not significantly different from the use of either medication alone.
      CONCLUSIONS: The benefit of ACE inhibitors and aspirin is consistent with what
      would be expected from overall results of randomized trials; prescribed together,
      the effect is slightly greater than with either one alone, but not significantly
      or substantially so.

PMID- 11252113
TI  - Relationship between smoking and weight control efforts among adults in the
      united states.
AB  - BACKGROUND: The effect of weight control concerns on smoking among adults is
      unclear. We examined the association between smoking behavior and weight control
      efforts among US adults. METHODS: A total of 17 317 adults responded to the Year
      2000 Supplement of the 1995 National Health Interview Survey (83% combined
      response rate). Respondents provided sociodemographic and health information,
      including their smoking history and whether they were trying to lose weight,
      maintain weight, or gain weight. RESULTS: Rates of smoking were lower among
      adults who were trying to lose or maintain weight than among those not trying to
      control weight (25% vs 31%; P<.001). After adjustment for sex, race, education,
      income, marital status, region of the country, and body mass index, the
      relationship between trying to lose weight and current smoking varied according
      to age. Among adults younger than 30 years, those trying to lose weight were more
      likely to smoke currently (odds ratio, 1.36 [95% confidence interval, 1.09
      1.70]), whereas older adults trying to lose weight were as likely or less likely
      to smoke compared with adults not trying to control weight. After adjustment,
      smokers of all ages who were trying to lose weight were more likely to express a
      desire to quit smoking. Results were similar after stratification by sex and body
      mass index. CONCLUSIONS: Adults younger than 30 years are more likely to smoke if
      they are trying to lose weight. However, smokers of all ages who are trying to
      lose weight are more likely to want to stop smoking. Patients' weight control
      efforts should not discourage clinicians from counseling about smoking cessation.
      Education about smoking and healthy weight control methods should target young
      adults.

PMID- 11252114
TI  - The cost-effectiveness of vaccination against Lyme disease.
AB  - BACKGROUND: Vaccination against Lyme disease appears to be safe and effective;
      however, the cost per quality-adjusted life-year (QALY) gained with vaccination
      is unknown. METHODS: We developed a decision-analytic model to evaluate the cost
      effectiveness of vaccination compared with no vaccination in individuals living
      in endemic areas of Lyme disease. Our analysis encompassed a 10-year time horizon
      including a 2-year vaccination schedule with an additional year of vaccine
      effectiveness. The costs and probabilities of vaccination risk, compliance and
      efficacy, and Lyme disease clinical sequelae and treatment were estimated from
      the literature. Health-related quality-of-life weights of the various clinical
      sequelae of Lyme disease infection were obtained from a sample of 105 residents
      from Nantucket Island, Massachusetts. RESULTS: Vaccinating 10 000 residents
      living in endemic areas with a probability of Lyme disease per season of 0.01
      averted 202 cases of Lyme disease during a 10-year period. The additional cost
      per QALY gained compared with no vaccination was $62 300. Vaccination cost $12
      600/QALY gained for endemic areas with an attack rate of 2.5% per season, and
      $145 200/QALY gained for an attack rate of 0.5%. Vaccinating individuals over an
      accelerated 2-month vaccination schedule improved the cost-effectiveness to $53
      700/QALY gained. If a yearly booster shot is required for persisting efficacy,
      the marginal cost-effectiveness ratio increases to $72 700/QALY. The cost
      effectiveness of vaccination was most sensitive to the Lyme disease treatment
      efficacy and assumptions about the persistence of vaccination effect. CONCLUSION:
      Vaccination against Lyme disease appears only to be economically attractive for
      individuals who have a seasonal probability of Borrelia burgdorferi infection of
      greater than 1%.

PMID- 11252115
TI  - Diagnosis of pulmonary alveolar proteinosis: usefulness of papanicolaou-stained
      smears of bronchoalveolar lavage fluid.
AB  - BACKGROUND: The globules (stained green, orange, or orange in the center coated
      with a green rim) seen in Papanicolaou-stained smears of bronchoalveolar lavage
      fluid are suggested to be characteristic of pulmonary alveolar proteinosis (PAP).
      OBJECTIVE: To evaluate the usefulness of Papanicolaou-stained smears of
      bronchoalveolar lavage fluid in aiding a diagnosis of PAP. METHODS: Papanicolaou
      stained smears of bronchoalveolar lavage fluid obtained from 7 patients (5
      idiopathic, 2 secondary) with PAP were evaluated. To serve as controls, the
      smears of 11 normal subjects and 128 patients with other pulmonary disorders were
      also examined. The findings on the presence and number of globules were recorded.
      To differentiate PAP from other pulmonary disorders, the highest globule value
      obtained from the control group was chosen as the cutoff point. RESULTS: The
      characteristic globules were not found in normal subjects and only found in 6 of
      128 patients with other pulmonary disorders. Their clinical diagnoses were
      Sjogren syndrome in 2 cases; polymyositis, idiopathic pulmonary fibrosis,
      asbestosis, and hypersensitivity pneumonitis in 1 case each. The numbers of
      globules in these 6 patients were 1, 3, 17, 7, 3, and 2. In contrast, more than
      100 globules were found in all patients with PAP. The number of globules was
      highly sensitive and specific in aiding a diagnosis of PAP when the cutoff value
      was set at 18. CONCLUSION: The globules seen in Papanicolaou-stained smears of
      bronchoalveolar lavage fluid may be valuable in aiding a diagnosis of PAP,
      especially when the number of globules is more than 18.

PMID- 11252116
TI  - The impact of the introduction of a rapid D-dimer assay on the diagnostic
      evaluation of suspected pulmonary embolism.
AB  - BACKGROUND: Rapid D-dimer assays are being used in the diagnostic evaluation of
      suspected pulmonary embolism (PE). Although this hypothesis is anticipated to
      decrease the use of ventilation-perfusion (VQ) scans and other diagnostic tests
      for PE, it has not been tested in a "real-world" environment. SUBJECTS AND
      METHODS: A randomized prospective trial was conducted on 470 of the 5390 enrolled
      patients aged 60 years and older who had previously undergone any diagnostic
      tests for PE at an urban teaching hospital. The use of D-dimer as part of the
      diagnostic evaluation for PE was promulgated in the 2 randomly chosen
      intervention firms. The remaining 2 firms served as controls. MAIN OUTCOME
      MEASURES: The number of VQ scans, spiral computed tomographic scans, and
      pulmonary angiograms performed. Secondary outcomes included mortality and
      thromboembolic or bleeding events during 3 months of follow-up. RESULTS: Of the
      470 inpatients who underwent evaluation for PE on a per PE workup basis, fewer VQ
      scans were performed in the intervention firms (63.8% vs 81.3%; P<.01). However,
      the number of patients evaluated for PE nearly doubled in the intervention firms
      (304 vs 166; P<.01), so that more VQ scans were performed in the intervention
      than in the control firms (194 vs 135; P<.01). Ninety-four patients from the
      control firms and 160 patients from the intervention firms were diagnosed and
      treated for venous thromboembolic disease (P<.01). There were no differences in
      secondary outcomes during the 3-month follow-up. CONCLUSIONS: The introduction of
      a rapid D-dimer assay increased the number of VQ scans performed because the
      number of patients screened for PE increased. A larger number of patients in the
      intervention firms were diagnosed as having venous thromboembolic disease (PE
      and/or deep vein thrombosis). There were no perceived changes in mortality or
      venous thromboembolic events during the 3-month follow-up.

PMID- 11252117
TI  - Glycemic index and serum high-density lipoprotein cholesterol concentration among
      us adults.
AB  - BACKGROUND: Dietary glycemic index, an indicator of the ability of the
      carbohydrate to raise blood glucose levels, and glycemic load, the product of
      glycemic index and carbohydrate intake, have been positively related to risk of
      coronary heart disease. However, the relationships between glycemic index and
      glycemic load and high-density lipoprotein cholesterol (HDL-C) concentration in
      the US population are unknown. METHODS: Using data from 13 907 participants aged
      20 years and older in the Third National Health and Nutrition Examination Survey
      (1988-1994), we examined the relationships between glycemic index and glycemic
      load, which were determined from a food frequency questionnaire and HDL-C
      concentration. RESULTS: The age-adjusted mean HDL-C concentrations for increasing
      quintiles of glycemic index distribution were 1.38, 1.32, 1.30, 1.26, and 1.27
      mmol/L (P<.001 for trend). (To convert millimoles per liter to milligrams per
      deciliter, divide by 0.0259.) After additional adjustment for sex, ethnicity,
      education, smoking status, body mass index, alcohol intake, physical activity,
      energy fraction from carbohydrates and fat, and total energy intake, the mean HDL
      C concentrations for ascending quintiles of glycemic index were 1.36, 1.31, 1.30,
      1.27, and 1.28 mmol/L (P<.001 for trend). Adjusting for the same covariates and
      considering glycemic index as a continuous variable, we found a change in HDL-C
      concentration of -0.06 mmol/L per 15-unit increase in glycemic index (P<.001).
      The multiple R(2) for the model was 0.23. Similarly, the multivariate-adjusted
      mean HDL-C concentrations for ascending quintiles of glycemic load distribution
      were 1.35, 1.31, 1.31, 1.30, and 1.26 mmol/L (P<.001 for linear trend). The
      inverse relationships between glycemic index and glycemic load and HDL-C
      persisted across all subgroups of participants categorized by sex or body mass
      index. CONCLUSIONS: These findings from a nationally representative sample of US
      adults suggest that high dietary glycemic index and high glycemic load are
      associated with a lower concentration of plasma HDL-C.

PMID- 11252118
TI  - Aspirin and the treatment of heart failure in the elderly.
AB  - OBJECTIVES: We sought (1) to determine how often aspirin is prescribed as a
      discharge medication among patients 65 years or older and hospitalized with both
      heart failure and coronary artery disease; (2) to identify patient
      characteristics associated with the decision to prescribe aspirin; and (3) to
      evaluate the association between aspirin prescription at discharge and 1-year
      survival. METHODS: We performed a retrospective cohort study of consecutive
      Medicare beneficiary survivors of a hospitalization for heart failure at 18
      Connecticut hospitals (up to 200 hospitalizations per hospital) from 1994 to
      1995. RESULTS: Among the 1110 patients in the study sample who did not have a
      contraindication to aspirin, aspirin therapy was prescribed for 456 (41%) at
      discharge. Patients who were prescribed aspirin at discharge had a lower 1-year
      mortality after discharge than patients who were not prescribed aspirin (odds
      ratio, 0.71; 95% confidence interval, 0.54-0.94), even after adjustment for
      baseline differences in demographic, clinical, and treatment characteristics
      between the 2 groups. CONCLUSIONS: This study has identified a strong association
      between the use of aspirin and lower mortality in older patients with both heart
      failure and coronary artery disease. The benefit of aspirin is consistent with
      that expected from randomized trials of other groups of patients with vascular
      disease.

PMID- 11252119
TI  - Abdominal cross-sectional imaging for inpatients with abnormal liver function
      test results: yield and usefulness.
AB  - BACKGROUND: Abdominal cross-sectional imaging is often performed to evaluate
      abnormal liver function test (LFT) results in hospitalized patients. However, few
      data are available regarding the yield and usefulness of imaging inpatients for
      the indication of abnormal LFT results, the process of requesting abdominal
      imaging studies, or the response to their findings. METHODS: We retrospectively
      reviewed abdominal imaging scans that were obtained during a 27-month period. We
      matched the imaging studies done with the indication of abnormal LFT results; all
      scans were requested using computerized physician order entry. Reports were coded
      for interpretation and associated process step results. To determine the
      usefulness of the imaging studies, a random sample of patient charts with
      positively coded imaging studies were reviewed. Imaging examinations were
      considered useful if they provided new diagnostic information and/or changed
      subsequent patient care. RESULTS: Of 6494 abdominal imaging studies, 856 were
      performed for the indication of abnormal LFT results and matched to both image
      reports and laboratory results. Report coding judged 37% of interpretations as
      clinically significant, including 27% with "positive" (abnormal results and
      explain the abnormal LFT results) examinations. Among the positive examinations,
      the most common diagnoses were biliary obstruction (25%), cholecystitis (21%),
      malignancy (20%), and cirrhosis (14%). Positively coded reports provided new
      clinical information in 63% of these studies and changed patient care in 42% of
      cases. Process measures assessed provision of additional information to and from
      radiologists (69% and 8%, respectively) and the frequency with which the findings
      of current abdominal imaging studies were compared with those of prior studies
      (59%). CONCLUSION: Abdominal cross-sectional imaging studies performed on
      inpatients with abnormal LFT results had a high diagnostic yield and frequently
      changed patient care.

PMID- 11252120
TI  - Impact of diet on blood pressure and age-related changes in blood pressure in the
      US population: analysis of NHANES III.
AB  - BACKGROUND: The impact of diet on blood pressure and the age-related changes in
      blood pressure have been difficult to detect within one population. We designed
      this analysis to study the association of major dietary factors with blood
      pressure and with age-related changes in blood pressure in a representative
      sample of the US population. METHODS: Data were obtained on all individuals 20
      years or older (n = 17 030) surveyed in the Third National Health and Nutrition
      Examination Survey (NHANES III), including demographic data, anthropometric data,
      dietary intake (sodium, potassium, calcium, magnesium, protein, alcohol, and
      total energy) based on 24-hour recall, and blood pressure. Multivariate models
      relating diet to blood pressure were constructed using stepwise regression, best
      subset regression, and multiple regression. RESULTS: Systolic blood pressure was
      positively associated with higher sodium, alcohol, and protein intakes (P<.05)
      and negatively associated with potassium intake (P =.003). Diastolic blood
      pressure was negatively associated with potassium and alcohol intakes (P<.001).
      Pulse pressure was positively associated with sodium, protein, and alcohol
      intakes (P<.001). A higher intake of calcium (P =.01) was associated with a lower
      rate of rise in systolic blood pressure with age. CONCLUSION: A diet low in
      sodium, alcohol, and protein is associated with lower systolic blood and pulse
      pressure. Potassium intake was associated with lower systolic and diastolic blood
      pressure, whereas alcohol intake was associated with lower diastolic blood
      pressure. In addition, the age-related changes in systolic blood pressure were
      attenuated by higher calcium and protein intakes. Magnesium was not associated
      with any changes in blood pressure.

PMID- 11252121
TI  - High short-term mortality in hospitalized patients with advanced dementia: lack
      of benefit of tube feeding.
AB  - BACKGROUND: The influence of tube feeding on survival in hospitalized patients
      with advanced dementia is controversial. OBJECTIVE: To assess long-term survival
      in an inception cohort, incident tube feeding placement during the index
      hospitalization, and the influence of tube feeding on survival in this group of
      patients. SUBJECTS AND METHODS: Ninety-nine hospitalized patients with advanced
      dementia and an available surrogate decision maker were followed up through and
      after the index hospitalization for mortality and placement of a feeding tube.
      Other variables measured included advance directive status, presence of a long
      term primary care physician, level of involvement of the surrogate decision
      maker, admitting diagnosis, prior hospitalizations, comorbidities, and diagnosis
      related group diagnostic category. RESULTS: A new feeding tube was placed in 50%
      (51/99) of the study patients during the index hospitalization, 31% (31/99) left
      the hospital without a feeding tube, and 17% (17/99) were admitted with a feeding
      tube already in place. By stepwise logistic regression analysis, predictors of
      new feeding tube placement included African American ethnicity (odds ratio, 9.43;
      95% confidence interval, 2.1-43.2) and residence in a nursing home (odds ratio,
      4.9; 95% confidence interval, 1.02-2.5). Median survival of the 99 patients was
      175 days. Eighty-five (85%) survived the index hospitalization, and 28 (28%) were
      still alive at last follow-up, a range of 1.3 to 4.2 years after enrollment in
      the study. Tube feeding was not associated with survival (P =.90). An admitting
      diagnosis of infection was associated with higher mortality (odds ratio, 1.9; 95%
      confidence interval, 1.01-3.6). CONCLUSIONS: In this cohort of hospitalized
      patients with advanced dementia, risk of receiving a new feeding tube is high,
      associated with African American ethnicity, and prior residence in a nursing
      home, and has no measurable influence on survival. With or without a feeding
      tube, these patients have a 50% six-month median mortality.

PMID- 11252123
TI  - Hyperthermia and chronic pancerebellar syndrome after cocaine abuse.
AB  - We describe a patient who developed pancerebellar syndrome as a result of
      hyperthermia that developed after cocaine use. The patient had long-standing
      schizophrenia and had been taking risperidone for 2 years, without evidence of
      abnormal movements. A literature review revealed a marked similarity between
      cocaine and neuroleptics in their ability to cause hyperthermia. Based on our
      observations and the compatible evidence from the literature, we suggest that
      cocaine use may cause hyperthermia and result in chronic pancerebellar
      dysfunction.

PMID- 11252122
TI  - Early clinical outcomes and routine management of patients with non-ST-segment
      elevation myocardial infarction: a nationwide perspective.
AB  - BACKGROUND: Myocardial infarction (MI) in the absence of electrocardiographic ST
      segment elevation or new bundle branch block is the cause of hospitalization for
      a large and steadily increasing proportion of patients with acute ischemic chest
      pain. Despite its prevalence, the common demographic features, current hospital
      based management, and short-term clinical outcome among patients with non-ST
      segment elevation MI remain poorly defined. METHODS: A total of 183 113 patients
      with non-ST-segment elevation MI were identified in the National Registry of
      Myocardial Infarction database. Using a validated model, 43 928 patients (24.0%)
      were retrospectively placed in major, 34 917 (19.1%) in intermediate, and 104 268
      (56.9%) in minor severity clinical event categories that included hospital death,
      recurrent myocardial ischemia, and nonfatal recurrent MI. RESULTS: The
      administration of widely available and universally recommended pharmacologic
      therapies, including aspirin and beta-adrenergic blocking agents, was suboptimal,
      particularly among patients with major severity clinical events. In contrast,
      coronary angiography and mechanical revascularization procedures were commonplace
      (>60% of all patients) and most frequently performed in patients within the minor
      (compared with the major) severity clinical event category (58.2% and 42.7%,
      respectively). CONCLUSIONS: Patients with non-ST-segment elevation MI are a
      heterogeneous population, with readily identifiable demographic characteristics
      and clinical features associated with important early outcomes, including death.
      Nationwide efforts directed toward maximizing pharmacologic therapy utilization
      and the performance of invasive procedures according to established guidelines
      must continue.

PMID- 11252124
TI  - Granulomatous mastitis: an uncommon cause of breast abscess.

PMID- 11252125
TI  - Fluoxetine (Prozac) as a cause of QT prolongation.

PMID- 11252126
TI  - The future of integrative medicine.

PMID- 11252127
TI  - Are afternoon naps health hazards?

PMID- 11252129
TI  - Dry eyes and dry mouth in patients with generalized nodal osteoarthritis.

PMID- 11252131
TI  - Predicting outcomes after cardiopulmonary resuscitation.

PMID- 11252133
TI  - Pelvic pain: a chronic visceral pain syndrome.
AB  - Patients with chronic pelvic pain are usually evaluated and treated by
      gynecologists, gastroenterologists, urologists, and internists. In many patients
      with chronic pelvic pain the examination and work-up remain unrevealing and no
      specific cause of the pain can be identified. In these cases it is important to
      recognize that pain is not only a symptom of pelvic disease, but that the patient
      is suffering from a chronic pelvic pain syndrome. Once the diagnosis of chronic
      pelvic pain is made, treatment should be directed to symptomatic pain management.
      This article outlines treatment options currently available. Despite the
      challenge inherent in the management of chronic pelvic pain, many patients can be
      treated successfully using a multidisciplinary pain management approach. The
      first important step is to recognize that patients with chronic pelvic pain might
      suffer from a chronic visceral pain syndrome.

PMID- 11252135
TI  - Chronic urologic pain syndromes.
AB  - Chronic pains typically evaluated by a urologist are discussed from the
      perspective of a non-urologist pain clinician. The pathophysiology of some pains
      is understood and so we believe the patient's symptoms: examples are cancer
      related pain and recurrent urolithiasis. We treat these pains with traditional
      analgesics. Other pains, such as those of interstitial cystitis, chronic
      prostatodynia, and chronic orchialgia are less understood and so are treated in a
      more conservative and often empiric fashion. Proposed therapies for these
      disorders are discussed.

PMID- 11252134
TI  - The role of the dorsal column pathway in visceral nociception.
AB  - Neurosurgeons have successfully used punctate midline myelotomy to relieve
      visceral cancer pain in human patients. Animal experiments demonstrate a visceral
      nociceptive pathway in the posterior column that is more effective than the
      spinothalamic tract in activating thalamic neurons, eliciting behavioral
      responses and triggering increases in regional cerebral blood flow. This visceral
      nociceptive pathway involves postsynaptic dorsal column neurons in the central,
      visceral processing region of the spinal cord. Axons from the sacral cord ascend
      near the midline and from the thoracic cord at the junction of the gracile and
      cuneate fasciculi.

PMID- 11252136
TI  - Gender differences and hormonal modulation in visceral pain.
AB  - Women seek healthcare and are diagnosed more frequently with chronic somatic and
      visceral pain conditions relative to men. These conditions tend not to be life
      threatening disorders, but rather ones that decrease people's quality of life,
      impinge on work and recreational activities, and increase healthcare resource
      utilization. With increased awareness of basic gender differences in biology and
      responsiveness to therapies, there has been renewed interest in factors which may
      account for the gender disparity in chronic visceral pain conditions. Basic and
      clinical evidence primarily from patients with irritable bowel syndrome has
      provided initial insights into visceral pain sensitivity, perception, and
      responsitivity.

PMID- 11252137
TI  - Visceral pain in humans: lessons from animals.
AB  - Acute and persistent neuropathic and inflammatory injuries of healthy animals
      have contributed importantly to our current understanding of nociception and
      pain. Studies have differentiated somatic from visceral nociceptive input, and
      elucidated the pathways of transduction, transmission, perception, and modulation
      of the input. Other animal studies have identified important genetic and
      environmental influences on responses to nociception. Studies of naturally
      occurring visceral pain syndromes in animals also have added to our understanding
      of comparable syndromes in humans. Because of the aversive nature of pain, use of
      healthy animals to study pain in the service of other animals and humans is a
      decision to be taken carefully, and carries with it the responsibility of
      treating the animals as humanely as possible.

PMID- 11252138
TI  - Premonitory symptoms in cluster headache.
AB  - Cluster headache is one of the most excruciating headaches affecting human beings
      -especially the male sex. Most of the cluster headache cases are of episodic
      nature, with active cluster periods lasting generally between a few weeks and 2
      or 3 months. A still undetermined percentage of patients report nonpainful
      sensations preceding the onset of the pain attack for a variable period of time.
      If occurring only a few minutes or a few hours before the onset of pain, such
      symptoms are called prodromal. When occurring for several days, weeks, or months
      before the pain, they are termed premonitory symptoms. The author believes that
      premonitory symptoms have not been properly diagnosed and emphasizes the need to
      investigate their presence, because by knowing them advances can be made in the
      understanding of the physiopathology of this particular cephalalgia. Furthermore,
      it can also allow the physician to be ahead, by giving preventive treatment and
      stopping or diminishing the intensity and duration of the pain attacks.

PMID- 11252139
TI  - Hypothalamic involvement and activation in cluster headache.
AB  - Cluster headache is an episodic form of primary neurovascular headache that is
      both severe and relatively rare. It is characterized by episodes of headache with
      cranial parasympathetic activation and sympathetic impairment that come in bouts,
      or clusters. Its pathophysiology can be divided into understanding the attack
      phenotype and the biotype of the periodicity. Acute attacks of cluster headache
      are marked by trigeminal nerve-mediated pain and with cranial autonomic
      activation, trigeminal-autonomic cephalalgia; an activation that characterizes
      the phenotype of a group of headaches. The signature feature of cluster headache
      is its periodicity, the daily cycle of attacks when the patient is in an active
      bout, or the circumannual, or other period, cycling that distinguishes the on
      period from the off period. Functional brain imaging with positron emission
      tomography and structural imaging with voxel-based morphometry have identified an
      area in the posterior hypothalamic gray as key in understanding cluster headache.
      This area is subtly enlarged in its gray matter volume, active during an acute
      cluster headache but inactive when patients are challenged between bouts. Cluster
      headache is likely to be a form of primary neurovascular pain whose phenotypic
      expression relies on the trigeminal-autonomic reflex, with a biotype determined
      by the brain area, the posterior hypothalamus, in which the lesion seems to be
      located. Understanding both the phenotypic expression and the biotype will,
      respectively, enable better acute attack treatments and better preventative
      management of this horrible form of headache.

PMID- 11252140
TI  - Migrainous features in cluster headache.
AB  - Migraine and cluster headache have been considered entirely separate clinical
      syndromes, both in routine clinical practice and in the 1988 International
      Headache Society classification. Neurologists seeing large numbers of patients
      soon realize, however, that there is a considerable overlap between the two
      conditions. Some patients have attacks with the cardinal features of cluster
      headache, but also have a few symptoms (especially a visual aura) usually
      attributed to migraine. In addition, it is not uncommon for a patient with a
      lifetime's history of migraine to experience a typical bout of cluster headache,
      although the reverse is less common. This article reviews the published series of
      such patients.

PMID- 11252141
TI  - Pathophysiology of primary headaches.
AB  - The cerebral circulation is innervated by sympathetic, parasympathetic, and
      sensory nerves, which store a considerable number of neurotransmitters. The role
      of these has been evaluated in primary headaches. A clear association between
      head pain and the release of calcitonin gene-related peptide was demonstrated. In
      cluster headache and in a case of chronic paroxysmal headache there was in
      addition the release of vasoactive intestinal peptide, which was associated with
      the facial symptoms (nasal congestion, rhinorrhea). In parallel with sumatriptan
      treatment, head pain subsided and neuropeptide release normalized. These data
      show the involvement of sensory and parasympathetic mechanisms in the
      pathophysiology of primary headaches.

PMID- 11252142
TI  - The use of baclofen in cluster headache.
AB  - Cluster headache is a rare, clinically well-characterized disabling disorder that
      occurs in both episodic and chronic forms. The very painful short-lived
      unilateral headache attacks are associated with autonomic dysfunction. A large
      number of drugs such as ergotamines, steroids, methysergide, lithium carbonate,
      verapamil, valproate, capsaicin, leuprolide, clonidine, methylergovine maleate,
      methylphenidate, and melatonin are considered beneficial for prophylaxis.
      Nevertheless, this extremely painful condition is occasionally refractory to
      conventional treatment. The antispastic agent baclofen has been shown to possess
      an antinociceptive activity. Its efficacy in neuralgias, central pain following
      spinal lesions, painful strokes, migraine, and medication misuse chronic daily
      headache suggests that it may be useful for prevention of cluster headache
      attacks. Therefore, we treated 16 symptomatic patients with cluster headache with
      daily baclofen, 15 to 30 mg, in three divided doses for the cluster period and 2
      weeks after. Within a week, 12 patients reported the cessation of attacks. One
      was substantially better and became attack free by the end of the following week.
      In the remaining three patients, the attacks worsened and corticosteroids were
      prescribed. One of these was also given verapamil. Three of the 16 patients had
      an additional cluster period, which cleared with a second course of baclofen. In
      this pilot study, baclofen seemed to be effective, safe, and well tolerated for
      cluster headache, and seemed to retain its efficacy on repeated clusters.

PMID- 11252143
TI  - Treatment and management of cluster headache.
AB  - Cluster headache is an uncommon yet well-defined neurovascular syndrome occurring
      in both episodic and chronic varieties. The most striking feature of cluster
      headache is the unmistakable circadian and circannual periodicity. Inheritance
      may play a role in some families. The attacks are of extreme intensity, of short
      duration, occur unilaterally, and are accompanied by signs and symptoms of
      autonomic dysfunction. In contrast to migraine, during an attack the cluster
      patient prefers to pace about. Attacks frequently occur at night. Although the
      pathophysiology of cluster headache remains to be fully elucidated, several
      seminal observations have recently been made. The medical treatment of cluster
      headache includes both acute therapy aimed at aborting individual attacks and
      prophylactic therapy aimed at preventing recurrent attacks during the cluster
      period. Agents used for acute therapy include inhalation of oxygen, sumatriptan,
      and dihydroergotamine. Transitional prophylaxis involves the short-term use of
      either corticosteroids or ergotamine derivatives. The cornerstone of maintenance
      prophylaxis is verapamil, yet methysergide, lithium, and divalproex sodium may
      also be employed. In some patients, melatonin or topiramate may be useful
      adjunctive therapies.

PMID- 11252144
TI  - Quantitative assessment of neuropathic pain.
AB  - Quantitative sensory testing (QST) refers to a group of protocols that allows for
      quantitative measures of somesthetic function. Several protocols evaluate
      perceptual threshold, whereas others evaluate perception of stimuli above
      threshold. Each protocol has its own advantages and disadvantages, but one must
      always weigh a trade-off between accuracy (with longer protocols) and expediency
      (with shorter protocols). In assessing patients with neuropathic pain, one is
      interested in both positive and negative sensory symptoms. QST studies, using
      either neuropathic pain patients or healthy volunteers who have been rendered
      temporarily hyperalgesic, have demonstrated that pain abnormalities can be
      modality specific. The fact that various pain abnormalities can exist
      independently of each other suggests that (at least partially) different
      neuropathologic processes are responsible for each one. Current research suggests
      that both peripheral sensitization and central sensitization play a role in these
      abnormal pain conditions, and identification of precise neuropathologic
      mechanisms is under active investigation.

PMID- 11252145
TI  - Complex regional pain syndromes.
AB  - Complex regional pain syndromes (CRPS) (formerly reflex sympathetic dystrophy and
      causalgia) are neuropathic pain conditions that are initiated by an extremity
      trauma or peripheral nerve lesion. Clinical definition and scientific
      understanding of CRPS are still evolving; however, both the clinical picture and
      therapeutic options are significantly influenced by a dysfunction of the
      sympathetic nervous system. Recent investigations suggest functional central
      abnormalities and a peripheral inflammatory component in the pathophysiology of
      CRPS. Interdisciplinary treatment includes physical, pharmacologic, and invasive
      interventional therapy, as well as stimulation techniques.

PMID- 11252146
TI  - Psychological assessment and treatment of patients with neuropathic pain.
AB  - Studies on the psychological assessment and treatment of neuropathic pain
      conditions, including postherpetic neuralgia (PHN), diabetic neuropathy, complex
      regional pain syndrome, post spinal cord injury, post amputation, and AIDS
      related neuropathy, are reviewed. Although limited information is currently
      available, the findings are consistent with the larger literature on chronic pain
      and indicate that the assessment of neuropathic pain needs to include measurement
      of multiple dimensions of quality of life. Mood, physical and social functioning,
      and pain-coping strategies such as catastrophizing and social support are all
      important domains. Clinical trials of psychological interventions have not been
      reported in the scientific literature. Case series of successful treatment of
      neuropathic pain are reported, primarily in the area of biofeedback. As with
      other chronically painful conditions, it is likely that cognitive-behavioral
      interventions will improve the quality of life in neuropathic pain conditions.

PMID- 11252147
TI  - Stimulation methods for neuropathic pain control.
AB  - Neurostimulation methods for control of chronic neuropathic pain have recently
      gained in popularity. The reasons for this are multifactorial. As opposed to
      nerve ablation, these methods are minimally invasive and reversible. The
      improvements in hardware design simplified implantation techniques and prolonged
      equipment longevity. Stimulation trials have become less invasive, allowing
      patients to test its effects before final implantation. Finally, the scientific
      evidence has shown good outcomes of neurostimulation methods for chronic
      neuropathic pain control. Recent research efforts have revealed new potential
      mechanisms of action of neurostimulation. Whereas its action was widely explained
      by gate control theory in the past, it seems that neuromodulation acts also by
      modulation of neurotransmitters in the central nervous system. Three
      neurostimulation methods are currently used in clinical practice: spinal cord
      stimulation (SCS), peripheral nerve stimulation (PNS), and deep brain stimulation
      (DBS). The SCS and PNS are excellent treatment choices for certain forms of
      neuropathic pain. The new indications for SCS are end-stage peripheral vascular
      disease and ischemic heart disease, whereas PNS is used for the treatment of
      occipital neuralgia and chronic pelvic pain. DBS is reserved for carefully
      selected patients in whom the other treatment modalities have failed. In a
      minority of patients the "tolerance" to neurostimulation develops after long-term
      use. Further research is needed to establish better outcome predictors to
      neurostimulation and possibly improve patient selection criteria.

PMID- 11252150
TI  - Migraine variants.
AB  - The term "migrant variant" is not used in the headache classification of the
      International Headache Society (IHS), but it includes those forms of migraine
      that are not typical of migraine with or without aura. Headaches that do not
      quite fulfill all of the IHS criteria are termed "migrainous disorder." Migraine
      associated with auras arising from unusual sites includes basilar migraine,
      retinal migraine, and ophthalmoplegic migraine. Two of the chromosomal sites for
      hemiplegic migraine have been identified. Migraine aura may occur without
      headache and an aura may be prolonged. Migrainous infarct has occurred when the
      aura lasts more than 1 week or imaging studies are positive and other etiologies
      have been ruled out. If the migraine attack is prolonged beyond 3 days the term
      "status migrainousus" is applied.

PMID- 11252148
TI  - Pharmacologic treatment of neuropathic pain.
AB  - Neuropathic pain, or pain after nervous system injury, can be very refractory to
      pharmacologic interventions. Through a better understanding of the
      pathophysiology of neuropathic pain, it has been suggested that nonopioid agents,
      such as antidepressants and anticonvulsants, may be more efficacious in the
      treatment of neuropathic pain than common analgesics, such as opioids or
      nonsteroidal anti-inflammatory drugs. However, this has not been consistently
      demonstrated in clinical studies. Conversely, many confounding factors of
      neuropathic pain make it difficult to interpret clinical studies. Therefore, we
      must develop a better understanding of the preclinical models of neuropathic pain
      to better understand the application of new and old drugs to the human
      neuropathic pain state. This article provides an overview of the commonly used
      preclinical neuropathic pain models, followed by a summary of the efficacy of
      currently available agents in preclinical pain models and human correlates.

PMID- 11252149
TI  - Pathophysiologic mechanisms of neuropathic pain.
AB  - New animal models of peripheral nerve injury have facilitated our understanding
      of neuropathic pain mechanisms. Nerve injury increases expression and
      redistribution of newly discovered sodium channels from sensory neuron somata to
      the injury site; accumulation at both loci contributes to spontaneous ectopic
      discharge. Large myelinated neurons begin to express nociceptive substances, and
      their central terminals sprout into nociceptive regions of the dorsal horn.
      Descending facilitation from the brain stem to the dorsal horn also increases in
      the setting of nerve injury. These and other mechanisms drive various pathologic
      states of central sensitization associated with distinct clinical symptoms, such
      as touch-evoked pain.

PMID- 11252151
TI  - How to pick optimal acute treatment for migraine headache.
AB  - Drug selection for the acute treatment of migraine is based on comorbid
      disorders, coexistent diseases, and the patient's pain profile and specific needs
      and expectations. Patients should be instructed to tailor their treatment
      strategy to meet their specific needs by varying their medications according to
      pain intensity. This will aid in successful headache management, by increasing
      compliance and decreasing disability and cost.

PMID- 11252152
TI  - Pathophysiology of migraine headache.
AB  - The underlying mechanism of migraine and pain has been unraveled recently with
      the advent of neuroimaging. In this article mechanism of migraine aura and the
      pain of migraine are discussed. In addition, interictal studies demonstrating
      hyperexcitability in migraine are reviewed.

PMID- 11252153
TI  - Diagnostic issues in migraine.
AB  - Headache poses diagnostic challenges to the clinician for many reasons. It is an
      extremely common complaint, and may be associated with acute illness or serious
      pathology such as brain tumor or cerebral aneurysm. However, the majority of
      patients experiencing recurrent headache in the population suffer either from a
      variant of tension-type headache or migraine. Because migraine is more likely to
      be disabling, it becomes the most likely diagnosis for any patient presenting
      with recurrent headache interfering with function. Although the diagnostic
      criteria developed by the International Headache Society in 1998 are useful as a
      guide, migraine may be more readily recognized in a clinical setting by its
      consideration at the top of the differential for patients presenting with
      recurrent headache. This article reviews the standard diagnostic criteria for
      migraine, while also addressing the primary and secondary headache syndromes that
      may be considered in a differential diagnosis. The indications and roles for
      specific investigative procedures such as neuroimaging are reviewed. Specific
      emphasis is placed on the clinical recognition of migraine in the context of an
      assortment of headache conditions.

PMID- 11252154
TI  - Epidemiology of migraine.
AB  - Migraine is a highly prevalent headache disorder that has a substantial impact on
      the individual and society. Over the past decade, substantial advances in
      research have increased understanding of the pathophysiology, diagnosis,
      epidemiology, and treatment of the disorder. This article reviews data on the
      epidemiology and impact of migraine. It also highlights the increased awareness
      of migraine, citing examples from the popular media and the Internet.

PMID- 11252156
TI  - MICE, a program to track and monitor animals in animal facilities.
AB  - BACKGROUND: A growing number of laboratories are using the mouse as a model
      system in developmental biology as well as in molecular biology. Surprisingly,
      most of these laboratories do not have reliable computerized systems to track
      these animals, and the few commercial solutions available are expensive. We thus
      developed MICE (Mouse Information and Classification Entity), a program aimed at
      facilitating the monitoring of animals in animal facilities. RESULTS: This
      program consists of a virtual facility in which scientists can perform all the
      tasks done in the real world (i.e., receiving animals, breeding them, preparing
      cage labels, etc.). Recording of each animal (birth date, cage number, ID number,
      tail analysis number, parents, genetic status, genetic background, etc.) enables
      reliable tracking. According to any parameter of interest, animals can then be
      identified, grouped, sorted, moved, and so forth. Crossings are automatically
      processed by the program. For example, new genetic backgrounds, generation
      number, and anticipated due dates are determined. The program also reminds the
      user when new births are expected and entering newborn animals only requires a
      few clicks. The genealogy of each animal can be determined in two different ways,
      one being the visualization of a genealogical tree from which information of
      ancestors can be retrieved. CONCLUSION: This standalone program, that will be
      distributed free of charge to academic laboratories requesting a license,
      represents a new and valuable tool for all animal facility users, and permits
      simple and reliable tracking and retrieving of animals.

PMID- 11252155
TI  - Menstrual migraine: diagnosis and treatment.
AB  - Of the nearly 20 million American women suffering with migraine, approximately 12
      million experience a worsening of their migraines in association with their
      menstrual cycle. Prior to puberty the prevalence of migraine is slightly higher
      in boys; however, after puberty there is an emerging female predominance.
      Estrogen likely plays an important role in explaining this gender difference;
      however, hormones unlikely explain the entire epidemiologic variation. This
      article reviews the diagnosis and treatment options for menstrually associated
      migraine.

PMID- 11252157
TI  - Estrogen protects against the synergistic toxicity by HIV proteins,
      methamphetamine and cocaine.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) infection continues to increase at
      alarming rates in drug abusers, especially in women. Drugs of abuse can cause
      long-lasting damage to the brain and HIV infection frequently leads to a
      dementing illness. To determine how these drugs interact with HIV to cause CNS
      damage, we used an in vitro human neuronal culture characterized for the presence
      of dopaminergic receptors, transporters and estrogen receptors. We determined the
      combined effects of dopaminergic drugs, methamphetamine, or cocaine with
      neurotoxic HIV proteins, gp120 and Tat. RESULTS: Acute exposure to these
      substances resulted in synergistic neurotoxic responses as measured by changes in
      mitochondrial membrane potential and neuronal cell death. Neurotoxicity occurred
      in a sub-population of neurons. Importantly, the presence of 17beta-estradiol
      prevented these synergistic neurotoxicities and the neuroprotective effects were
      partly mediated by estrogen receptors. CONCLUSION: Our observations suggest that
      methamphetamine and cocaine may affect the course of HIV dementia, and
      additionally suggest that estrogens modify the HIV-drug interactions.

PMID- 11252159
TI  - Sulfate Reduction Dynamics and Enumeration of Sulfate-Reducing Bacteria in
      Hypersaline Sediments of the Great Salt Lake (Utah, USA).
AB  - Bacterial sulfate reduction activity (SRA) was measured in surface sediments and
      slurries from three sites in the Great Salt Lake (Utah, USA) using radiolabeled
      35S-sulfate. High rates of sulfate reduction (363 +/- 103 and 6,131 +/- 835 nmol
      cm-3 d-1) were measured at two sites in the moderately hypersaline southern arm
      of the lake, whereas significantly lower rates (32 +/- 9 nmol cm-3 d-1) were
      measured in the extremely hypersaline northern arm. Bacterial sulfate reduction
      was strongly affected by salinity and showed an optimum around 5-6% NaCl in the
      southern arm and an optimum of around 12% NaCl in the more hypersaline northern
      arm of the lake. High densities of sulfate-reducing bacteria (SRB) ranging from
      2.2 x 107 to 6.7 x 108 cells cm-3 were determined by a newly developed tracer MPN
      technique (T-MPN) employing sediment media and 35S-sulfate. Calculation of
      specific sulfate reduction rates yielded values comparable to those obtained in
      pure cultures of SRB. However, when using a conventional MPN technique with
      synthetic media containing high amounts of Fe(II), the numbers of SRB were
      underestimated by 1-4 orders of magnitude as compared to the T-MPN method. Our
      results suggest that high densities of slightly to moderately halophilic and
      extremely halotolerant SRB are responsible for the high rates of sulfate
      reduction measured in Great Salt Lake sediments.

PMID- 11252158
TI  - Change of dopamine receptor mRNA expression in lymphocyte of schizophrenic
      patients.
AB  - BACKGROUND: Though the dysfunction of central dopaminergic system has been
      proposed, the etiology or pathogenesis of schizophrenia is still uncertain partly
      due to limited accessibility to dopamine receptor. The purpose of this study was
      to define whether or not the easily accessible dopamine receptors of peripheral
      lymphocytes can be the peripheral markers of schizophrenia. RESULTS: 44 drug
      medicated schizophrenics for more than 3 years, 28 drug-free schizophrenics for
      more than 3 months, 15 drug-naive schizophrenic patients, and 31 healthy persons
      were enrolled. Sequential reverse transcription and quantitative polymerase chain
      reaction of the mRNA were used to investigate the expression of D3 and D5
      dopamine receptors in peripheral lymphocytes. The gene expression of dopamine
      receptors was compared in each group. After taking antipsychotics in drug-free
      and drug-naive patients, the dopamine receptors of peripheral lymphocytes were
      sequentially studied 2nd week and 8th week after medication. In drug-free
      schizophrenics, D3 dopamine receptor mRNA expression of peripheral lymphocytes
      significantly increased compared to that of controls and drug-medicated
      schizophrenics, and D5 dopamine receptor mRNA expression increased compared to
      that of drug-medicated schizophrenics. After taking antipsychotics, mRNA of
      dopamine receptors peaked at 2nd week, after which it decreases but the level was
      above baseline one at 8th week. Drug-free and drug-naive patients were divided
      into two groups according to dopamine receptor expression before medications, and
      the group of patients with increased dopamine receptor expression had more severe
      psychiatric symptoms. CONCLUSIONS: These results reveal that the molecular
      biologically-determined dopamine receptors of peripheral lymphocytes are
      reactive, and that increased expression of dopamine receptor in peripheral
      lymphocyte has possible clinical significance for subgrouping of schizophrenis.

PMID- 11252160
TI  - Archaeal Biodiversity in Crystallizer Ponds from a Solar Saltern: Culture versus
      PCR.
AB  - The culturable haloarchaeal diversity in a crystallizer pond from a solar saltern
      has been analyzed and compared with the biodiversity directly retrieved by
      analysis of rRNA genes amplified from the environment. Two different sets of
      culture conditions have been assayed: solid medium with yeast extract as carbon
      source and liquid media with either yeast extract or a mixture of fishmeal,
      Spirulina sp., and Artemia salina. Seventeen colonies grown on plates with yeast
      extract incubated at 30 degrees C were analyzed by 16S rDNA partial sequencing.
      Sixteen were closely related to haloarchaea of the genus Halorubrum; 13 of them
      to Halorubrum coriense, a haloarchaeon isolated from a solar saltern pond in
      Australia, which had not been previously isolated from the pond analyzed in this
      study; and one to Haloarcula marismortui. Liquid cultures were analyzed by
      ribosomal internal spacer analysis (RISA) and partial sequencing of the 16SrRNA
      genes. A total of 18 sequences were analyzed, 15 corresponding to RISA bands
      obtained from cultures, and 3 from the environmental sample used as inoculum.
      Thirteen sequences obtained from cultures were related to several Halorubrum
      species, and 2 to Haloarcula. One of the clones obtained directly from the
      environmental sample was distantly related to a Natronobacterium, whereas two
      were related to SPhT, the phylotype most frequently retrieved from this
      environment by culture independent techniques. Our results show an extremely low
      diversity for the haloarchaea retrieved by cultivation even when modifications to
      the standard technique are introduced.

PMID- 11252161
TI  - Microbial Community Composition and Ecology of an Acidic Aquatic Environment: The
      Tinto River, Spain.
AB  - We studied the correlation between physicochemical and biological characteristics
      of an acidic river, the Tinto River, in Southwestern Spain. The Tinto River is an
      extreme environment characterized by its low pH (mean of 2.2) and high
      concentrations of heavy metals (Fe 2.3 g/L, Zn 0.22 g/L, Cu 0.11 g/L). These
      extreme conditions are the product of the metabolic activity of chemolithotrophic
      microorganisms, including iron- and sulfur-oxidizing bacteria, that can be found
      in high concentrations in its waters. The food chain in the river is very
      constrained and exclusively microbial. Primary productivity in the Tinto River is
      the sum of photosynthetic and chemolithotrophic activity. Heterotrophic bacteria
      and fungi are the major decomposers and protists are the major predators. A
      correlation analysis including the physicochemical and biological variables
      suggested a close relationship between the acidic pH values and abundance of both
      chemolithotrophic bacteria and filamentous fungi. Chemolithotrophic bacteria
      correlated with the heavy metals found in the river. A principal component
      analysis of the biotic and abiotic variables suggested that the Tinto River
      ecosystem can be described as a function of three main groups of variables: pH
      values, metal concentrations, and biological productivity.

PMID- 11252162
TI  - Diazotrophy in Modern Marine Bahamian Stromatolites.
AB  - N2 fixation (nitrogenase activity), primary production, and diazotrophic
      community composition of stromatolite mats from Highborne Cay, Exuma, Bahamas,
      were examined over a 2-year period (1997-1998). The purpose of the study was to
      characterize the ecophysiology of N2 fixation in modern marine stromatolites.
      Microbial mats are an integral surface component of these stromatolites and are
      hypothesized to have a major role in stromatolite formation and growth. The
      stromatolite mats contained active photosynthetic and diazotrophic assemblages
      that exhibited temporal separation of nitrogenase activity (NA) and
      photosynthesis. Maximal NA was detected at night. Seasonal differences in NA and
      net O2 production were observed. Photosynthetic activity and the availability of
      reduced organic carbon appear to be the key determinants of NA. Additions of the
      de novo protein synthesis inhibitor chloramphenicol did not inhibit NA in March
      1998, but greatly inhibited NA in August 1998. Partial sequence analysis of the
      nifH gene indicates that a broad diversity of diazotrophs may be responsible for
      NA in the stromatolites.

PMID- 11252163
TI  - Bacterioplankton Dynamics in Estuarine Mesocosms: Effects of Tank Shape and Size.
AB  - Mesocosms provide a powerful tool for investigating bacterial dynamics at small
      scales; however, even these controlled studies are not exempt from spatial
      influences. Differences in mesocosm shape and size may have profound effects on
      the enclosed community since these features may influence the behavior of the
      system. Studies were conducted in mesocosms of varying dimensions (narrow, deep
      and wide, shallow tanks) and volumes (0.1, 1, and 10 m3) in an attempt to
      decipher effects attributable to changes in container size and shape. Both
      mesocosm volume and shape affected the course of bacterial growth following
      containment. Bacterial abundance and production were high in both groups of 0.1
      m3 tanks and in the large, wide, shallow tanks with the greatest light supply at
      depth. Differences in bacterial growth between differently shaped tanks (i.e.,
      differing wall area to volume ratios) were observed among equal volume
      enclosures, with faster growth in the wide/shallow tanks. Light availability,
      phytoplankton growth, and primary production differed among tanks, and bacterial
      growth and production were correlated with these properties. During high nutrient
      conditions, mesocosm volume and shape influenced bacterial growth, possibly
      because of periphyton growth on walls in small tanks and elevated light levels in
      wide/shallow tanks. These results suggest the importance of considering container
      dimensions when designing and interpreting mesocosm experiments and may allow
      deeper understanding of the fundamental processes underlying patterns observed in
      the real world.

PMID- 11252164
TI  - The Responses of a Natural Bacterioplankton Community to Different Levels of
      Ultraviolet-B Radiation: A Food Web Perspective.
AB  - With the continuing increase of ultraviolet-B radiation (UVBR: 280-320 nm) fluxes
      toward the Earth's surface, there is concern regarding a possible negative impact
      on heterotrophic bacterioplankton. The effects of enhanced UVBR on a natural
      bacterioplankton community were studied during a 7-day experiment conducted in
      mesocosms (1500 L). Four light regimes were tested: natural light, 280 to 313 nm
      excluded UVBR, and two levels of UVBR enhancement. During the first 3 days of the
      experiment characterized by high inorganic nutrient concentrations (nitrates > 1
      umol L-1 and ammonium > 0.1 umol L-l), UVBR had no effect on both bacterial
      abundances and activities. From day 4 to the end of the experiment, nitrate
      concentrations remained low (

PMID- 11252165
TI  - Nitrate Regeneration Coupled to Degradation of Different Size Fractions of DON by
      the Picoplankton in the Elbe Estuary.
AB  - Bacterial conversion of high (HMW > 3,000 Da) and low (LMW < 3,000 Da) molecular
      weight DON (dissolved organic nitrogen) was studied along the freshwater section
      of the Elbe estuary during the summer of 1997. Indigenous populations of
      picoplankton were incubated in a flow-through chamber that allowed a constant
      exchange of sterile, filtered Elbe water as the culture medium for the
      microorganisms, which remained within the chamber. Nitrogen conversion was
      followed by changes in the concentrations of total and low molecular weight DON
      and dissolved inorganic nitrogen compounds, the uptake of O2, and bacterial
      growth. Along the Elbe estuary, total DON concentrations varied between 0.69 and
      1.1 mg N L-1, of which between 64 and 79% was LMW-DON. Ammonium was a minor
      nutrient present in the Elbe at concentrations below 0.26 mg N L-1. During
      incubation in the laboratory between 27 and 64% of the LMW-DON was consumed at
      rates ranging from 24 to 51 ug N L-1 h-1. HMW-DON was used only when the
      degradable LMW-DON pool became exhausted and accounted for between 60 and 100% of
      the HMW-DON. This produced an increase in the DON consumption rate between 43 and
      79 ug N L-1 h-1. Nitrification rates were independent of the external ammonium
      concentration until it decreased to below 1 ug N-NH4 L-1. Most of the N in the
      nitrification process originated as NH4 regenerated from DON. Between 75 and 100%
      of the LMW-DON and ammonium consumed was rapidly converted to nitrate. This
      amount decreased to between 65 and 85% when HMW-DON was consumed in addition to
      the LMW-DON. DON and ammonium consumption supported nitrification rates up to 71
      ug N L-1 h-1. The amount of DOC (dissolved organic carbon) degraded was not
      equivalent to the C:N ratio of the total dissolved organic matter. Calculations
      based on oxygen consumption for respiration and ammonium regeneration revealed
      that the substrates used during the incubations contained C:N at ratios of about
      3:1. These results suggest that the nitrogen-rich compounds had been removed from
      the dissolved organic matter and subsequently consumed by bacteria, while the
      carbon skeleton remained mostly unaffected by the degradation processes.

PMID- 11252166
TI  - Expression and chromosomal mapping of the mouse smooth muscle calponin gene.
AB  - Smooth muscle calponin (Cnn1) is a multifunctional protein whose expression is
      tightly restricted to differentiated smooth muscle cell (SMC) lineages during
      embryonic and post-natal life. As such, Cnn1 represents an ideal locus from which
      to dissect out regulatory elements that control its expression and hence the
      mature SMC phenotype. Previous work has focused on the expression and chromosomal
      mapping of the rat and human Cnn1 orthologs. In this report, we describe a unique
      pattern of Cnn1 expression during the growth and differentiation of BC3H1 cells,
      a mouse cell line that has transcriptional characteristics of both smooth and
      skeletal muscle lineages. Actively growing BC3H1 cells exhibit Cnn1 mRNA
      expression, which is extinguished when these cells are induced to differentiate
      upon serum withdrawal. Replating differentiated BC3H1 cells restores steady-state
      Cnn1 mRNA levels. The down-regulation of Cnn1 mRNA during BC3H1 differentiation
      coincides with the induction of myogenin, a skeletal muscle transcription factor
      that is not present in SMC lineages. Results from cycloheximide and actinomycin D
      studies suggest the existence of a labile repressor protein(s) that destabilizes
      the pool of Cnn1 mRNA and/or silences transcription of the Cnn1 locus. Mapping of
      the mouse Cnn1 locus to Chr 9, which is homologous to human Cnn1 on 19p13.2 and
      rat Cnn1 on 8q, suggests no gross rearrangement of this locus in the BC3H1 cell
      line. These results are the first to show reversible expression of Cnn1 and
      demonstrate the utility of the BC3H1 muscle cell line as a model system for the
      further characterization of Cnn1 gene regulation.

PMID- 11252167
TI  - Molecular cloning, genetic mapping, and expression of the mouse Sf3b1 (SAP155)
      gene for the U2 snRNP component of spliceosome.
AB  - SAP155, a subunit of the U2 snRNP, is essential for prespliceosome assembly and
      splicing catalysis of the major spliceosome. Moreover, the protein has been
      identified in the minor (U12-dependent) spliceosome. These facts strongly suggest
      that SAP155 is shared by two distinct complexes owing to its importance in the
      removal of any type of intron. Here we have isolated a cDNA encoding the 146-kDa
      mouse homolog, designated Sf3b1. The amino acid sequence of Sf3b1 is very highly
      conserved among homologs from Schizosaccharomyces pombe (52.4% identity) to human
      (99.6%), and the C-terminal 825 residues of these Sf3b1 homologs show even higher
      identities. This C-terminal region shows significant similarity to the PR65
      subunit of protein phosphatase 2A, which is composed of 15 tandem repeats of a 39
      amino acid sequence. Mouse genome analyses showed Sf3bh1 to be a single-copy gene
      mapping to the central part of Chromosome (Chr) 1. Northern blot analysis and
      whole mount in situ hybridization revealed Sf3b1 to be ubiquitously expressed in
      a variety of adult tissues and mid-gestation embryos.

PMID- 11252168
TI  - Analysis of candidate genes included in the mammary cancer susceptibility 1
      (Mcs1) region.
AB  - The rat strain COP is resistant to spontaneous and carcinogen-induced mammary
      cancer, whereas the strain WF is susceptible. Using genetic linkage analysis of
      (WF x COP) F1 x WF backcrosses, LC Hsu, LA Shepel and co-workers showed that a
      region at the centromeric end of Chromosome (Chr) 2 (2q1) segregates with the
      sensitivity to mammary cancer development. The responsible locus was named Mcs1
      (for mammary cancer susceptibility 1). We have developed the chromosome map of
      the 2q1 region by localizing 18 genes, 4 ESTs, and several anonymous markers,
      using radiation hybrids and fluorescence in situ hybridization. The region
      containing Mcs1 was delineated to 2q12-q14. Five of the genes (Mef2c, Map1b,
      Ccnh, Rasa, Rasgrf2) were assigned to this region and were shown to be expressed
      in the rat mammary glands, while three possible functional candidate genes,
      Pi3kr1, Rad17, and Naip, were excluded from the critical region. Since cyclin H,
      encoded by Ccnh, plays an important role in the control of the cell cycle and
      since the proteins encoded by Rasa and Rasgrf2 control the activity of the RAS
      oncoprotein, the corresponding genes appeared as both functional and positional
      Mcs1 candidates. RT-PCR experiments on RNA extracted from mammary glands of the
      two rat strains (COP, WF) was done. No amino acid sequence difference was found
      between the two strains. These results argue against the hypothesis that any of
      these three genes is Mcs1.

PMID- 11252169
TI  - Genetic analysis of cataract in Ihara epileptic rat.
AB  - We analyzed the mode of inheritance of cataract in the Ihara epileptic rat (IER)
      by crossing experiments, and mapped cataract-related genes by linkage analysis.
      Cataract did not develop in the F1 animals, but it developed in both male and
      female animals of backcross and F2. The occurrence rate of cataract was 48.5% in
      the backcross progeny and 19.4% in the F2 progeny. Thus, the character was
      considered to be inherited by the autosomal recessive mode. We found two groups
      that differed according to the time of onset among the backcross and F2 progeny:
      an early-onset group (EOG), in which cataracts developed by about 4 months after
      birth, and a late-onset group (LOG), in which cataracts developed 8 months or
      more after birth. Linkage analysis indicated the presence of one cataract gene
      each on Chromosome (Chr) 8 and Chr 15, and the cataract was demonstrated to be
      governed by more than one gene. The gene on Chr 8 was named Catil, and that on
      Chr 15. Cati2. Catil was involved in the occurrence of cataract, and the
      conditions required for cataract to develop were Cati1i/Cati1i or Cati1i/Cati1w.
      However, in the cataract rats with Cati1i/ Cati1w, the allele of Cati2 was always
      Cati2i/Cati2i. Cati2 was involved in the timing of onset of the cataract, and the
      precondition for early onset was Cati2i/Cati2i.

PMID- 11252170
TI  - Canine homolog of the T-box transcription factor T; failure of the protein to
      bind to its DNA target leads to a short-tail phenotype.
AB  - Domestic dog breeds show a wide variety of morphologies and offer excellent
      opportunities to study the molecular genetics of phenotypic traits. We are
      interested in exploring this potential and have begun by investigating the
      genetic basis of a short-tail trait. Our focus has been on the T gene, which
      encodes a T-box transcription factor important for normal posterior mesoderm
      development. Haploinsufficiency of T protein underlies a short-tail phenotype in
      mice that is inherited in an autosomal dominant fashion. We have cloned the dog
      homolog of T and mapped the locus to canine Chromosome (Chr) 1q23. Full sequence
      analysis of the T gene from a number of different dog breeds identified several
      polymorphisms and a unique missense mutation in a bob-tailed dog and its bob
      tailed descendants. This mutation is situated in a highly conserved region of the
      T-box domain and alters the ability of the T protein to bind to its consensus DNA
      target. Analysis of offspring from several independent bobtail x bobtail crosses
      indicates that the homozygous phenotype is embryonic lethal.

PMID- 11252171
TI  - Interleukin-8 haplotype structure from nucleotide sequence variation in
      commercial populations of U.S. beef cattle.
AB  - The aim of the present study was twofold: first, to design a panel of 96 sires
      that reflects the breadth of genetic diversity in U.S. beef cattle, and second,
      to use this panel to discover nucleotide sequence diversity and haplotype
      structures of interleukin (IL)-8 in commercial populations. The latter is a
      requisite for epidemiological studies designed to test whether IL8 alleles are
      risk factors for acquiring or maintaining bacterial infections in production
      environments. IL-8 encodes a proinflammatory cytokine that plays a central role
      in cell-mediated immunity by attracting and activating neutrophils in the early
      stages of host defense against bacterial invasion. Seven single-nucleotide
      polymorphism (SNP) markers were identified by sequencing two IL8 DNA segments
      amplified from the panel of 17 popular cattle breeds (MARC beef cattle diversity
      panel, version 2.1). Assays for automated genotype scoring by matrix-assisted
      laser desorption/ ionization time-of-flight mass spectrometry (MALDI-TOF MS) were
      developed to independently verify the seven SNP alleles in the 96 bulls and 313
      cattle from the MARC reference population. Five haplotype structures, spanning
      the two IL8 DNA segments, were unambiguously defined for the set of seven IL8
      SNPs. Based on the breadth of germplasm in bovine diversity panel, the five
      haplotype structures for IL8 are estimated to represent >98% of those present in
      these DNA segments in commercial populations of U.S. beef cattle. The frequencies
      of the five respective haplotypes in the eight Angus sires of the diversity panel
      (0.75, 0.25, 0.00, 0.00. 0.00) were similar to those scored in 150 purebred Angus
      cattle from six herds in four Midwestern states (0.82, 0.18, 0.01, 0.00 0.00),
      suggesting that the diversity panel may also be useful for estimating allele
      frequencies in commercial populations.

PMID- 11252172
TI  - Synteny of orthologous genes conserved in mammals, snake, fly, nematode, and
      fission yeast.
AB  - Four mouse genes, programmed cell death 2 (Pdcd2 or Rp8), brain protein 44-like
      (Brp441), bystin-like (Bysl), and uncoordinated-93-like (Unc931) genes were
      mapped to Chromosome (Chr) 17. The orthologs of these and other mouse Chr 17
      genes are localized on Chr III of Caenorhabditis elegans, thus defining a
      syntenic group conserved between vertebrates and nonvertebrates. In human, mouse,
      and snake, the PDCD2-, and TATA-binding protein (TBP)-encoding genes are adjacent
      tail-to-tail. The TBP- and PDCD2-encoding genes are linked also in Drosophila,
      and, together with proteasomal subunit C5 gene, they are syntenic in human,
      mouse, C. elegans, and Schizosaccharomyces pombe. The orthologs of tightly linked
      C. elegans genes, coding for BRP44L and PDCD2, map to about 2-Mb interval on
      human region 6q27 and on mouse Chr 17. Hitherto, 13 members of synteny conserved
      between C. elegans and vertebrates have been detected, of which six are located
      on Drosophila Chr X. Such a distribution of transcription units is nonrandom and
      could indicate a long-range cis-acting relationship among the genes within the
      conserved syntenic group.

PMID- 11252173
TI  - Comparative analysis of the genomic organization of Pax9 and its conserved
      physical association with Nkx2-9 in the human, mouse, and pufferfish genomes.
AB  - As a first step towards the identification of cis-regulatory elements of Pax9 by
      means of comparative genomics, we have analyzed genome regions encompassing the
      Pax9 gene in three vertebrate species, humans, mice (Mus musculus), and the
      Japanese pufferfish (Fugu rubripes). We show the genomic organization of Pax9 and
      its physical association with Nkx2-9 conserved in the three species. We discuss
      about possible implications of the conserved synteny between Pax9 and Nkx2-9 in a
      context of vertebrate evolution. This report also includes the first description
      of the primary structures of Fugu Pax9 and Nkx2-9. Furthermore, we report the
      identification of a novel upstream exon and putative transcription start sites in
      mouse Pax9. Our results suggest that transcription of Pax9 may be initiated at
      two alternative start sites and driven by TATA-less promoters.

PMID- 11252174
TI  - Fine mapping of Hyplip1 and the human homolog, a potential locus for FCHL.
AB  - Familial combined hyperlipidemia (FCHL) is a common genetic dyslipidemia
      predisposing to premature coronary heart disease (CHD). We previously identified
      a locus for FCHL on human Chromosome (Chr) 1q21-q23 in 31 Finnish FCHL families.
      We also mapped a gene for combined hyperlipidemia (Hyplip1) to a potentially
      orthologous region of mouse Chr 3 in the HcB-19/Dem mouse model of FCHL. The
      human FCHL locus was, however, originally mapped about 5 Mb telomeric to the
      synteny border, the centromeric part of which is homologous to mouse Chr 3 and
      the telomeric part to mouse Chr 1. To further localize the human Hyplip1 homolog
      and estimate its distance from the peak linkage markers, we fine-mapped the
      Hyplip1 locus and defined the borders of the region of conserved synteny between
      human and mouse. This involved establishing a physical map of a bacterial
      artificial chromosome (BAC) contig across the Hyplip1 locus and hybridizing a set
      of BACs to both human and mouse chromosomes by fluorescence in situ hybridization
      (FISH). We narrowed the location of the mouse Hyplip1 gene to a 1.5-cM region
      that is homologous only with human 1q21 and within approximately 5-10 Mb of the
      peak marker for linkage to FCHL. FCHL is a complex disorder and this distance
      may, thus, reflect the well-known problems hampering the mapping of complex
      disorders. Further studies identifying and sequencing the Hyplip1 gene will show
      whether the same gene predisposes to hyperlipidemia in human and mouse.

PMID- 11252175
TI  - In the QTL region surrounding porcine MHC, gene order is conserved with human
      genome.
AB  - On the porcine genome, the region surrounding the Major Histocompatibility
      Complex, also called Swine Leukocyte Antigens (SLA), is of particular interest
      not only owing to itq role in the control of immune response, but also because of
      its influence on many traits such as growth, fatness, and meat quality. To help
      in the identification of responsible genes, detailed comparative maps of the MHC
      region in mammalian species and powerful mapping tools allowing accurate ordering
      of genes and markers in this region are needed. In this report, we describe the
      use of the recently developed IMpRH radiation hybrid panel, to construct a higher
      density radiation hybrid map of swine Sscr 7p-q12, containing 23 additional loci.
      Our results show that the gene order is conserved between the two MHC-containing
      regions, even if an inversion is observed above the QTL region in the region
      containing DEK, SCA1, and EDN1 genes. The framework map produced shows that the
      IMpRH panel permits the ordering of genes and markers in the three MHC classes
      and would thus allow accurate localization of ESTs and candidate genes.

PMID- 11252176
TI  - Mapping of the pogo gene, a new ataxic mutant from Korean wild mice, on central
      mouse chromosome 8.

PMID- 11252177
TI  - Construction of a rabbit bacterial artificial chromosome (BAC) library:
      application to the mapping of the major histocompatibility complex to position
      12q.1.1.

PMID- 11252178
TI  - Chromosome heterozygosity and de novo chromosome rearrangements in mammalian
      interspecies hybrids.

PMID- 11252179
TI  - Hormonal control of ventral diaphragm myogenesis during metamorphosis of the
      moth, Manduca sexta.
AB  - Both the proliferation and differentiation of ventral diaphragm myoblasts are
      controlled by ecdysteroid during metamorphosis of the moth, Manduca sexta, but
      the responses have different hormonal requirements. Tonic exposure to moderate
      levels of ecdysteroid are required to stimulate myoblast proliferation. This is
      due to the presence of an ecdysteroid-dependent control point in the G(2) phase
      of the cell cycle. As a result, proliferation can be repeatedly turned on or off
      simply by adjusting the concentration of ecdysteroid to be above or below a
      critical threshold concentration. In contrast, high levels of ecdysteroid trigger
      irreversible proliferative arrest and differentiation of myofibers. Myoblast
      proliferation and differentiation also differ in their response to the juvenile
      hormone mimic, methoprene. Ecdysteroid-dependent proliferative arrest and
      differentiation are blocked by coculture with methoprene but methoprene has no
      effect on ecdysteroid-dependent proliferation. In the animal, premature exposure
      to high levels of ecdysteroid in the absence of juvenile hormone triggers
      precocious differentiation of the myoblasts, resulting in the formation of
      several thin bands of muscle rather than a complete diaphragm. Thus, ecdysteroid
      and juvenile hormone collaborate to determine the size and shape of the adult
      musculature.

PMID- 11252181
TI  - The production and elimination of supernumerary blast cells in the leech embryo.
AB  - Different species of leech vary greatly in body size but all have 32 body
      segments. It is unclear how the development of this precise number of segments is
      regulated, although it is known that the teloblasts of the early leech embryo
      initially produce more than the required numbers of segment founder cells (blast
      cells). We used fluorescent dextrans to show that the M teloblast of the
      Helobdella robusta embryo produces a variable number of additional
      (supernumerary) cells. These cells fail to enter the germinal band (which
      contains cells of all lineages and gives rise to the adult leech), but detach
      from its posterior end and disappear. Our observations suggest that some suffer
      an increase in membrane permeability while others fuse with the M teloblasts, but
      that they do not undergo apoptosis. The supernumerary cells of different lineages
      detach from the germinal band at different times, suggesting that detachment is
      not triggered by a global signal acting simultaneously on all lineages. We tested
      the hypothesis that the elimination of the supernumerary m blast cells results
      from a requirement of m blast cells for close interactions with cells of the
      other lineages for their survival, a condition that would not be achieved by the
      last-born m blast cells that fail to enter the germinal band. We cultured
      isolated M teloblasts and found that they do produce blast cells that themselves
      divide, indicating that cells of the M lineage can survive in the absence of any
      interactions with cells of the other lineages.

PMID- 11252180
TI  - Maternal factors and the evolution of developmental mode: evolution of oogenesis
      in Heliocidaris erythrogramma.
AB  - Evolutionary change in developmental mode in sea urchins is closely tied to an
      increase in maternal provisioning. We examined the oogenic modifications involved
      in production of a large egg by comparison of oogenesis in congeneric sea urchins
      with markedly different sized oocytes and divergent modes of development.
      Heliocidaris tuberculata has small eggs (95 microm diameter) and the ancestral
      mode of development through feeding larvae, whereas H. erythrogramma has large
      eggs (430 microm diameter) and highly modified non-feeding lecithotrophic larvae.
      Production of a large egg in H. erythrogramma involved both conserved and
      divergent mechanisms. The pattern and level of vitellogenin gene expression is
      similar in the two species. Vitellogenin processing is also similar with the
      gonads of both species incorporating yolk protein from coelomic and hemal stores
      into nutritive cells with subsequent transfer of this protein into yolk granules
      in the developing vitellogenic oocyte. Immunocytology of the eggs of both
      Heliocidaris species indicates they incorporate similar levels of yolk protein.
      However, H. erythrogramma has evolved a highly divergent second phase of
      oogenesis characterised by massive deposition of non-vitellogenic material
      including additional maternal protein and lipid. Maternal provisioning in H.
      erythrogramma exhibits recapitulation of the ancestral vitellogenic program
      followed by a novel oogenic phase with hypertrophy of the lipogenic program being
      a major contributor to the increase in egg size.

PMID- 11252182
TI  - The Suppressor of fused gene, involved in Hedgehog signal transduction in
      Drosophila, is conserved in mammals.
AB  - The Suppressor of fused [Su(fu)] gene of Drosophila melanogaster encodes a
      protein containing a PEST sequence [sequence enriched in proline (P), glutamic
      acid (E), serine (S) and threonine (T)] which acts as an antagonist to the serine
      threonine kinase Fused in Hedgehog (Hh) signal transduction during embryogenesis.
      The Su(fu) gene isolated from a distantly related Drosophila species, D. virilis,
      shows significantly high homology throughout its protein sequence with its D.
      melanogaster counterpart. We show that these two Drosophila homologs of Su(fu)
      are functionally interchangeable in enhancing the fused phenotype. We have also
      isolated mammalian homologs of Su(fu). The absence of the PEST sequence in the
      mammalian Su(fu) protein suggests a different regulation for this product between
      fly and vertebrates. Using the yeast two-hybrid method, we show that the murine
      Su(fu) protein can interact directly with the Fused and Cubitus interruptus
      proteins, known partners of Su(fu) in Drosophila. These data are discussed in the
      light of their evolutionary relationships.

PMID- 11252183
TI  - Role of Notch pathway in terminal follicle cell differentiation during Drosophila
      oogenesis.
AB  - During Drosophila oogenesis the body axes are determined by signaling between the
      oocyte and the somatic follicle cells that surround the egg chamber. A key event
      in the establishment of oocyte anterior-posterior polarity is the differential
      patterning of the follicle cell epithelium along the anterior-posterior axis.
      Both the Notch and epithelial growth factor (EGF) receptor pathways are required
      for this patterning. To understand how these pathways act in the process we have
      analyzed markers for anterior and posterior follicle cells accompanying
      constitutive activation of the EGF receptor, loss of Notch function, and ectopic
      expression of Delta. We find that a constitutively active EGF receptor can induce
      posterior fate in anterior but not in lateral follicle cells, showing that the
      EGF receptor pathway can act only on predetermined terminal cells. Furthermore,
      Notch function is required at both termini for appropriate expression of anterior
      and posterior markers, while loss of both the EGF receptor and Notch pathways
      mimic the Notch loss-of-function phenotype. Ectopic expression of the Notch
      ligand, Delta, disturbs EGF receptor dependent posterior follicle cell
      differentiation and anterior-posterior polarity of the oocyte. Our data are
      consistent with a model in which the Notch pathway is required for early follicle
      cell differentiation at both termini, but is then repressed at the posterior for
      proper determination of the posterior follicle cells by the EGF receptor pathway.

PMID- 11252184
TI  - Isolation and characterization of a Bombyx vasa-like gene.
AB  - AcDNA for a vasa-like gene (BmVLG) was isolated from Bombyx mori. As with vasa in
      Drosophila, the expression is restricted to the germline in the larval (and pupal
      and adult?) stage, and the maternal transcript exists. However, the maternal
      transcript shows localized (germ anlage) distribution patterns, and after
      degradation of the transcript during germband formation the transcript within
      cells clustering in the midst of the germ anlage, which eventually give rise to
      germ cells, remains and continues to be expressed during subsequent
      embryogenesis; this contrasts to the case of vasa in Drosophila. These results
      not only indicate the usefulness of BmVLG as a germ cell marker but also suggest
      the usefulness of this gene (family) in the study of insect germ anlage
      formation.

PMID- 11252185
TI  - Two-color detection of mRNA transcript localizations in fish and fly embryos
      using alkaline phosphatase and beta-galactosidase conjugated antibodies.
AB  - A fast and simplified two-color in situ hybridization procedure for the
      simultaneous detection of two different mRNAs in whole-mounted zebrafish and
      Drosophila embryos is presented. Transcript distributions are detected in a
      single incubation step using a mixture of alkaline phosphatase and beta
      galactosidase coupled antibodies. The different transcripts are visualized in
      contrasting colors by the use of beta-galactosidase substrates that develop color
      precipitates (magenta, blue) easily distinguishable from those of the standard
      alkaline phosphatase substrates. This protocol can be followed by standard
      immunohistochemistry to detect the expression of a third gene (at the protein
      level) in a third color.

PMID- 11252186
TI  - Laparoscopic resection of an epiphrenic diverticulum of the esophagus.
AB  - Diverticulectomy of epiphrenic diverticula of the esophagus is conventionally
      performed via left thoracotomy. We report the case of a 57-year-old man who
      presented with an epiphrenic diverticulum that was resected using a
      transperitoneal laparoscopic technique.

PMID- 11252187
TI  - Laparoscopic excision of congenital bladder diverticulum in a child.
AB  - Laparoscopy is being used more and more often in pediatric surgery for diagnostic
      and therapeutic indications. We report the successful laparoscopic excision of a
      congenital bladder diverticulum in a 6-year-old child. The minimally invasive
      approach allowed for easy identification and dissection of the diverticulum and
      surrounding vital structures with minimal postoperative pain and a good cosmetic
      result.

PMID- 11252188
TI  - Laparoscopic procedures during the third trimester of pregnancy.
AB  - Pregnancy no longer is considered to be an absolute contraindication for
      laparoscopic procedures. Furthermore, clinically helpful guidelines are in place
      for laparoscopic procedures during pregnancy. However, laparoscopic operations in
      women in the third trimester have not yet been reported fully. We successfully
      operated on torsion of an ovarian cyst in a woman during her third trimester
      using laparascopic procedure. The patient experienced an uneventful recovery.

PMID- 11252189
TI  - Laparoscopic repair of a ruptured diaphragm secondary to blunt trauma.
AB  - The diagnosis of acute diaphragmatic rupture can be a challenge for even the most
      experienced clinician. The treatment of the rupture and its concomitant injuries,
      particularly in the elderly, can be associated with significant morbidity and
      mortality. The advent of laparoscopy for both the diagnosis and repair of this
      condition has allowed a more minimally invasive approach. We present the case of
      a 70-year-old woman who was hurt in a motor vehicle crash. On admission, her
      physical exam showed left upper quadrant tenderness and bruising. The chest
      radiograph was suggestive of a ruptured diaphragm. She was taken to the operating
      room and explored laparoscopically. After a thorough exploration of all the
      abdominal contents, a tear in the diaphragmatic hiatus to the right of the
      esophagus was noted. The stomach and small intestine were returned to the
      abdomen, and the diaphragmatic rupture was repaired. We conclude that
      laparoscopic exploration and repair of a ruptured diaphragm in a bluntly injured
      patient is a safe and effective option in selected cases.

PMID- 11252190
TI  - Endoscopic palliation for pancreatic cancer with expandable metal stents.
AB  - Pancreatic cancer is generally not amenable to curative resection. Consequently,
      therapeutic efforts for these patients are most commonly directed at palliation
      of symptoms. Historically, surgery has been considered the most effective method
      of providing relief for biliary and/or enteric obstruction. However, less
      invasive methods have become available that can provide effective relief of
      jaundice and duodenal obstruction. Surgeons should still play an integral role in
      the management of these patients. We present a case report in which self
      expanding metallic stents were used to relieve obstruction of the bile duct and
      duodenum in a patient with unresectable pancreatic cancer.

PMID- 11252201
TI  - What clinical features are useful in diagnosing strep throat?

PMID- 11252202
TI  - Do patients with local reactions to allergy shots require dosage reductions for
      subsequent injections?

PMID- 11252203
TI  - Is imipramine or buspirone treatment effective in patients wishing to discontinue
      long-term benzodiazepine use?

PMID- 11252204
TI  - Is rofecoxib safer than naproxen?

PMID- 11252205
TI  - Clinical inquiries. What is the best oral antifungal medication for tinea
      capitis?

PMID- 11252206
TI  - Clinical inquiries. How soon should serum potassium levels be monitored for
      patients started on diuretics?

PMID- 11252207
TI  - Which should come first: rigor or relevance?

PMID- 11252208
TI  - Addressing multiple problems in the family practice office visit.
AB  - OBJECTIVES: The purpose of the study was to describe the number of problems
      addressed during family practice outpatient visits, the nature of additional
      problems raised, how they affect the duration of the visit, and how well they are
      reflected in the billing record. STUDY DESIGN: Cross-sectional. POPULATION: We
      studied a total 266 randomly selected adult patient encounters representing 37
      physicians. OUTCOMES MEASURED: A problem was defined as an issue requiring
      physician action in the form of a decision, diagnosis, treatment, or monitoring.
      Visit duration and the number of billing diagnoses were also assessed. RESULTS:
      On average, 2.7 problems and 8 physician actions were observed during an
      encounter. More than one problem was addressed during 73% of the encounters; 36%
      of these additional problems were raised by the physician and 58% by the patient.
      On average, each additional problem increased the length of the visit by 2.5
      minutes (P<.001). The concordance between the number of problems observed and the
      number of problems on the billing sheet indicated a trend toward underbilling the
      number of problems addressed. CONCLUSIONS: Multiple problems are commonly
      addressed during family practice outpatient visits and are raised by both the
      physicians and the patients. Our findings suggest that current views of physician
      productivity and the billing record are poor indicators of the reality of
      providing primary care.

PMID- 11252209
TI  - Differences in institutional cesarean delivery rates-the role of pain management.
AB  - BACKGROUND: The objective of our study was to compare cesarean delivery rates for
      low-risk nulliparous women in a community hospital and a tertiary-level maternity
      hospital and to determine factors influencing those rates. METHODS: We performed
      a retrospective cohort study of 857 women who did not have obstetric risk
      factors. The association between hospital and cesarean delivery rate was examined
      in a multivariate analysis using logistic regression. In a follow-up cohort
      study, we observed labor management for 24 couples in the community and 26 in the
      tertiary hospital. RESULTS: The odds of having a cesarean birth (age-adjusted) at
      the tertiary center were 3.4 (95% confidence interval, 2.1-5.4) compared with the
      community hospital. Maternal age, cervical dilatation on first examination, and
      use of epidural analgesia were the primary factors associated with the difference
      in cesarean delivery rates, with epidural analgesia having the largest effect.
      Labor support between the 2 hospitals appeared to be similar with the exception
      of increased use of ambulation in the community hospital and fewer numbers of
      caregivers for each woman in labor. Women in the tertiary center were more often
      offered epidural analgesia. CONCLUSIONS: Differences in use of epidural analgesia
      may contribute to differences in institutional rates of cesarean delivery. Use of
      epidural analgesia may be related to use of ambulation, consistency of caregiver
      during labor, availability of epidural, and suggestion for its use by caregivers.

PMID- 11252210
TI  - Cesarean delivery and hospitals: size matters.

PMID- 11252211
TI  - Communication about prostate cancer between men and their wives.
AB  - OBJECTIVES: Metastatic prostate cancer is a serious disease that affects both men
      and their intimate partners. We explored the perceptions of men who have been
      treated for metastatic prostate cancer and the views of their wives regarding the
      changes that were caused by prostate cancer and its treatment. STUDY DESIGN: We
      conducted retrospective focus group interviews with married men and separate
      focus groups with their wives. POPULATION: Twenty married men (11 white and 9
      African American) with an average age of 69 years (range=60-82 years) and 7 of
      the wives (5 white and 2 African American) participated in our study. Thirteen of
      the men were treated with orchiectomy, and 7 received monthly hormone ablation
      therapy. OUTCOMES MEASURED: We compared the accounts of husbands and wives
      concerning the diagnosis and treatment of prostate cancer. RESULTS: The
      participants' accounts indicate little spousal communication about the
      implications of prostate cancer on their lives. In particular, couples appear to
      talk little about their emotions, worries, and fears. CONCLUSIONS: Although wives
      have a profound interest in their husbands' prostate cancer, actual communication
      about the disease, its treatment, and the feelings it evokes may be less than we
      believe. Noncommunication in marriages might indicate that these couples are at
      increased risk for poor adjustment to prostrate cancer.

PMID- 11252212
TI  - Group office visits change dietary habits of patients with coronary artery
      disease-the dietary intervention and evaluation trial (D.I.E.T.).
AB  - BACKGROUND: We evaluated the effectiveness of a low-cost group visit intervention
      for changing the dietary intake and lipid levels of patients with known coronary
      artery disease (CAD). METHODS: We performed a controlled random group assignment
      trial in 4 community outpatient clinics. The Dietary Intervention and Evaluation
      Trial randomized 97 patients with CAD to either a control group that followed the
      National Cholesterol Education Program's Step II-III diet plan (n=48) or an
      experimental group that received meal plans, recipes, and nutritional information
      during monthly group office sessions (n=49). Both groups received lipid-lowering
      medications and were followed-up over 12 months. We assessed dietary intake,
      fasting lipid profiles, hemoglobin A1C levels, and per member per month (PMPM)
      expense data. RESULTS: Food frequency data showed that eating fruits and
      vegetables and cooking with monounsaturated fat increased significantly in the
      experimental group compared with the control group at 1 year (P=.0072; P=.0001;
      P=.0004). The total PMPM expenses decreased for both groups (38% for the
      experimental group and 10% for the control group), but the cost difference was
      statistically nonsignificant (P=.2975). Both groups noted low-density lipoprotein
      reductions, significant only in the experimental group (P=.0035). CONCLUSIONS:
      Our study suggests that using group office visits for patients with CAD was an
      effective method for helping subjects make dietary changes and for improving
      lipid levels. Patients with known CAD and elevated lipid levels were willing to
      make significant lifestyle changes when offered a program that emphasizes healthy
      foods in a group visit format.

PMID- 11252215
TI  - Treatment of the patient with deep vein thrombosis.

PMID- 11252217
TI  - Palliative care for the elderly.

PMID- 11252218
TI  - Is teething in infants associated with fever or other symptoms?

PMID- 11252220
TI  - Does a hip protector reduce the risk of hip fracture in frail elderly patients?

PMID- 11252219
TI  - Should calcium channel blockers be used as first-line antihypertensive therapy?

PMID- 11252221
TI  - Is oral dexamethasone as effective as intramuscular dexamethasone for outpatient
      management of moderate croup?

PMID- 11252222
TI  - Process evaluation of a tailored multifaceted approach to changing family
      physician practice patterns improving preventive care.
AB  - BACKGROUND: We conducted a process evaluation of a multifaceted outreach
      facilitation intervention to document the extent to which the intervention was
      implemented with fidelity. We also hoped to gain insight into how facilitation
      worked to improve preventive performance. METHODS: We used 5 data collection
      tools to evaluate the implementation of the intervention, and a combination of
      descriptive, quantitative, and qualitative analyses. Triangulation was used to
      attain a complete understanding of the quality of implementation. Twenty-two
      intervention practices with a total of 54 physicians participated in a randomized
      controlled trial that took place in Southwestern Ontario, Canada. The key
      measures of process were the frequency and time involved to deliver intervention
      components, the scope of the delivery and the utility of the components, and
      physician satisfaction with the intervention. RESULTS: Of the 7 components in the
      intervention model, prevention facilitators (PFs) visited the practice most often
      to deliver the audit and feedback, consensus building, and reminder system
      components. All the study practices received preventive performance audit and
      feedback, achieved consensus on a plan for improvement, and implemented a
      reminder system. Ninety percent of the practices implemented a customized flow
      sheet, and 10% used a computerized reminder system. Ninety-five percent of the
      intervention practices wanted critically appraised evidence for prevention, 82%
      participated in a workshop with opinion leaders in preventive care, and 100%
      received patient education materials in a binder. Content analysis of the
      physician interviews and bivariate analysis of physician self-reported changes
      between intervention and control group physicians revealed that the audit and
      feedback, consensus building, and development of reminder systems were the key
      intervention components. Ninety-five percent of the physicians were either
      satisfied or very satisfied with the intervention, and 90% would have been
      willing to have the PF continue working with their practice. CONCLUSIONS: Primary
      care practices in Ontario can implement significant changes in their practice
      environments that will improve preventive care activity with the assistance of a
      facilitator. The main components for creating change are audit and feedback of
      preventive performance, achieving consensus on a plan for improvement, and
      implementing a reminder system.

PMID- 11252223
TI  - The effect of cluster randomization on sample size in prevention research.
AB  - BACKGROUND: This paper concerns the issue of cluster randomization in primary
      care practice intervention trials. We present information on the cluster effect
      of measuring the performance of various preventive maneuvers between groups of
      physicians based on a successful trial. We discuss the intracluster correlation
      coefficient of determining the required sample size and the implications for
      designing randomized controlled trials where groups of subjects (e.g., physicians
      in a group practice) are allocated at random. METHODS: We performed a cross
      sectional study involving data from 46 participating practices with 106
      physicians collected using self-administered questionnaires and a chart audit of
      100 randomly selected charts per practice. The population was health service
      organizations (HSOs) located in Southern Ontario. We analyzed performance data
      for 13 preventive maneuvers determined by chart review and used analysis of
      variance to determine the intraclass correlation coefficient. An index of "up-to
      datedness" was computed for each physician and practice as the number of a
      recommended preventive measure done divided by the number of eligible patients.
      An index called "inappropriateness" was computed in the same manner for the not
      recommended measures. The intraclass correlation coefficients for 2 key study
      outcomes (up-to-datedness and inappropriateness) were also calculated and
      compared. RESULTS: The mean up-to-datedness score for the practices was 53.5%
      (95% confidence interval [CI], 51.0%-56.0%), and the mean inappropriateness score
      was 21.5% (95% CI, 18.1%-24.9%). The intraclass correlation for up-to-datedness
      was 0.0365 compared with inappropriateness at 0.1790. The intraclass correlation
      for preventive maneuvers ranged from 0.005 for blood pressure measurement to 0.66
      for chest radiographs of smokers, and as a consequence required the sample size
      ranged from 20 to 42 physicians per group. CONCLUSIONS: Randomizing by practice
      clusters and analyzing at the level of the physician has important implications
      for sample size requirements. Larger intraclass correlations indicate
      interdependence among the physicians within a cluster; as a consequence,
      variability within clusters is reduced, and the required sample size increased.
      The key finding that many potential outcome measures perform differently in terms
      of the intracluster correlation reinforces the need for researchers to carefully
      consider the selection of outcome measures and adjust sample sizes accordingly
      when the unit of analysis and randomization are not the same.

PMID- 11252224
TI  - [Nikolai Vladimirovich Timofeev-Resovskii (1900-1981). (Essay on his life and
      works)].
AB  - The article contains a brief review of the basic works (1925-1981) written by
      Nikolay V. Timofeeff-Ressovsky--one of the famous geneticist of the elapsing
      century, the founder of radiobiology and radiation genetics, biocenology and
      radioecology, a prominent evolutionary biologist. In genetics, his name is
      associated with the development of fundamental problems of population genetics,
      phenogenetics, gene interaction and investigations of the role of environmental
      and genetic factors in expression of different characters. Timofeeff-Ressovsky
      classical works on mutagenesis process and especially, radiation mutagenesis,
      promoted penetration of methods and approaches applied in molecular physics and
      chemistry, into genetic analysis, and accelerated forming of the modern molecular
      genetics. A special place in the development of population genetics is occupied
      by the hypothesis of microevolutionary process developed by Nikolay V. Timofeeff
      Ressovsky along with other famous biologists in the end of the 30-ies. This
      hypothesis connected Darwin's evolutionary theory with rapidly developing
      concepts of genetics. In the last years of his life, Timofeeff-Ressovsky was
      especially interested in a global problem which was called by him "The Biosphere
      and Humanity". Here was especially strikingly shown the broadness of his approach
      to the analysis of the biosphere phenomena in the best traditions of the Russian
      natural science. In the course of time, the wealth of Nikolay V. Timofeeff
      Ressovsky's scientific heritage not only remains valuable, but also takes on more
      profundity and value.

PMID- 11252225
TI  - The A beta 6w302 gene and molecular mechanisms of resistance to the spread of
      radiation-induced lymphoma in a mouse mutant, survivor-27.
AB  - Metastatic tumors escape from immune response and spread in the body; survivors
      are very rare. Novel single exon genes A beta 4-7 and a pseudogene A beta 8 psi
      have been cloned from survivors. Their protein coding sequences are similar to
      MHC class II beta H2-Ab cDNA while their promoter is different from MHC
      promoters. The A beta 4 protein was demonstrated on macrophages (antigen
      presenting cells). The A beta gene family is genetically unstable in germ line
      and somatic cells of survivors. Mutants S-27 and S-87/1 lost the A beta 5s5 and
      acquired the A beta 6w302 gene; the Ab gene mutated in S-27. The proposed
      mechanism of resistance is molecular instability of the A beta gene family
      resulting in somatic mutations and wandering immune responses that destroy the
      tumor in the survivor.

PMID- 11252226
TI  - [Study of genome instability using DNA fingerprinting of the offspring of male
      mice subjected to chronic low dose gamma irradiation].
AB  - By a polymerase chain reaction with an arbitrary primer (AP-PCR), the possibility
      of transmission of genome instability to somatic cells of the offspring (F1
      generation) from male parents of mice exposed to chronic low-level gamma
      radiation was studied. Male BALB/c mice 15 days after exposure to 10-50 cGy were
      mated with unirradiated females. Biopsies were taken from tale tips of two month
      old offspring mice and DNA was isolated. The primer in the AP-PCR was a 20-mer
      oligonucleotide flanking the microsatellite locus Atp1b2 on chromosome 11 of the
      mouse. A comparative analysis of individual fingerprints of AP-PCR products on
      DNA-templates from the offspring of irradiated and unirradiated male mice
      revealed an increased variability of microsatellite-associated sequences in the
      genome of the offspring of the males exposed to 25 and 50 cGy. The DNA
      fingerprints of the offspring of male mice exposed to chronic irradiation with
      the doses 10 and 25 cGy 15 days before fertilization (at the post-meiotic stage
      of spermatogenesis) showed an increased frequency of "non-parent bands". The
      results of the study point to the possibility of transmission to the offspring
      somatic cells of changes increasing genome instability from male parents exposed
      to chronic low-level radiation prior to fertilization.

PMID- 11252227
TI  - [Independence of DNA repair after gamma irradiation and radioadaptive response in
      lymphocytes of patients with Bloom syndrome].
AB  - The evidence for independency of DNA repair and radioadaptive response (RAR) was
      obtained in cells of patients with Bloom syndrome. The cells of patients with
      Bloom syndrome (human autosomal recessive disorder) are characterized by
      chromosomal instability and increased risk of malignancy at an early age.
      Resynthesis of gamma-induced DNA breaks wasn't find in lymphocytes of 3 patients
      with Bloom syndrome while the level of RAR was the same as in the cells of
      healthy donors.

PMID- 11252229
TI  - [Radiation mapping as one of main methods of creating high resolution maps of
      human and animal genomes].
AB  - Radiation hybrid mapping (RH mapping) is considered as one of the main methods of
      constructing physical maps of mammalian genomes. In introduction, theoretical
      prerequisites of developing of the RH mapping and statistical methods of data
      analysis are discussed. Comparative characteristics of universal commercial
      panels of the radiation hybrid somatic cells (RH panels) are shown. In
      experimental part of the work, RH mapping is used to localise nucleotide
      sequences adjacent to NotI sites of human chromosome 3 with the aim to integrate
      contig map of NotI clones to comprehensive maps of human genome. Five nucleotide
      sequences adjacent to the sites of integration of papilloma virus in human genome
      and expressed in the cells of cervical cancer were localised. It was demonstrated
      that the region 13q14.3-q21.1 was enriched with nucleotide sequences involved in
      the processes of oncogenesis. RH mapping can be considered as one of the most
      perspective applications of the modern radiation biology in the field of
      molecular genetics, that is, in constructing physical maps of mammalian genomes
      with high resolution level.

PMID- 11252228
TI  - [Changes in the number of DNA-protein cross links in spleen lymphocytes of mice
      exposed to low intensity low dose gamma irradiation].
AB  - Levels of DNA-protein cross-links (DPC) and DNA single-strand breaks (SSB) in
      spleen lymphocytes were studied in mice exposed to low-intensity gamma-radiation
      (1.7 mGy/day) for 1, 4, 10, 20, and 30 days. The spleen mass and count of
      lymphocytes isolated from this organ also has been investigated. The significant
      increase in the DPC level as compared to the control occurred on the 10-th and 30
      th days of irradiation at doses of 1.7 and 5.1 cGy, accordingly. The number of
      spleen lymphocytes normalized to organ mass significantly decreased on the 4-th
      and 30-th days of the experiment. No increase was found in levels of alkali
      labile sites and SSB. In contrast, the increase in the amount of duplex form DNA
      was recorded on the 4-th and 30-th days of the experiment. Our indicate that DPC
      formation after irradiation at low doses represents some form of cellular
      response to the damaging agent.

PMID- 11252230
TI  - [Increased radiosensitivity after irradiation of lymphocytes low adaptive doses].
AB  - The variability of blood lymphocyte reaction on the adaptive irradiation (0.05 Gy
      at first, then 1.0 Gy 5 h later) was investigated by micronuclei assay. Blood
      samples were obtained from 700 children. It was shown that in all groups studied
      there were children with enhanced radiosensitivity ("radiosensitivity syndrome"
      RS) after exposure to adaptive low dose of radiation. The radiosensitivity
      syndrome occurred more often in groups of ill children; part of them was
      characterized by the enhanced blood content of immunoglobulin E, enhanced level
      of T helpers and T suppressors. A high spontaneous level of lymphocytes with
      micronucleus is a factor of radiosensitivity formation. The possible factors
      resulted in radiosensitivity syndrome are discussed.

PMID- 11252231
TI  - [Results of and prospects for methods of determination of the frequency of mutant
      cells for glycophorin A and T-cell receptor loci to estimate long-term genotoxic
      effect of ionizing radiation].
AB  - The usage of two methods for assessment of somatic gene mutations for the purpose
      of biological dosimetry and estimation of consequences of irradiation at long
      time after the exposure has been discussed. The determination of cells bearing
      mutated glycophorin A (GPA) locus is a reliable method for biodosimetry at both
      short and long time after the acute irradiation according to our results and the
      data of other authors. For prolonged exposure, the GPA-method is less informative
      than in cases of acute irradiation. The determination of mutant cell frequency at
      T-cell receptor (TCR) locus may be used only at short time after the irradiation.
      Meanwhile, the TCR-method is more sensitive and informative for biodosimetry of
      recent irradiation than the GPA test. The both methods may be used for individual
      assessment of long-term health consequences after the irradiation, because
      persons with elevated frequencies of mutant cells may represent a group at high
      risk in respect to oncological diseases.

PMID- 11252232
TI  - [Potential relationship between mutation process induced by low doses of ionizing
      radiation, and positional dynamics of chromosomes in nuclei of eukaryotic cells].
AB  - The mutation process has many stages. The information presented in this article
      suggest that a cell exposed to low LET radiation in the low-dose range (up to 1
      cGy) must almost completely repair all spontaneous and radiation-induced DNA
      lesions. But reparation of DNA double-stranded breaks (DSB), which are the basis
      of genome instability has peculiarity. We have shown that the mechanisms of
      action of low doses (which initiate natural antimutagenic reactions of resting
      cells--an adaptive response) are associated with chromosome loci (centromere)
      movement in a cell nucleus. We suggest that the movement of chromosome loci in
      cell nucleus is the fundamental mechanism for repair of DSB and switching of the
      transcription of gene (it is known that in case of lymphoid cells Ikaros
      complexes repressor is colocolizated with centromere loci); in particular, of
      nucleolar transcription activities because the latter is dependent on centromere
      arrangement. Because the movement of chromosome loci in both the mitotic cycle
      and under adapting dose on resting cells is much the same it could be assumed
      that in latter case the cells also lose their functional characteristic for
      differentiated resting cells. Under chronic exposure to low doses the functional
      changes can be the cause of organic changes if adapting dose affects the
      sufficient part of the cells. The role of cells of evolutional or ontogenetic
      reserve in mutation process is considered.

PMID- 11252233
TI  - [Genetic effects in Drosophila melanogaster induced by chronic low-dose
      irradiation].
AB  - It was investigated the influence of the chronic gamma-irradiation in the dose
      rate of 0.17 sGy/h on the rate of genetic variability in the laboratory strains
      of Drosophila melanogaster with genotypic distinguishes in mobile genetic
      elements and defects in the DNA repair processes. It was shown that the rates of
      induction of recessive lethal mutations depended on genotype of investigated
      strains. In the different strains we have observed an increase as well as a
      decrease of the mutation rate. Also in was established that irradiation leads to
      the frequencies of the GD-sterility and mutability of the snw and h(w+) in the P
      M and H-E dysgenic crosses. The obtained results suggest that mobile genetic
      elements play an important role in the forming of genetic effects in response to
      low dose irradiation.

PMID- 11252234
TI  - [Results of cytogenetic studies of the consequences of the Chernobyl accident].
AB  - The selected results of the cytogenetic studies of the Chernobyl accident
      consequences were summarised. The chromosomal aberrations were used as a method
      of biodosimetry for a dose assessment for victims during the initial period after
      the Chernobyl accident. A good correlation between doses calculated based on
      chromosomal aberrations (dicentrics) and severity of acute radiation syndrome
      observed in clinic was found. The biodosimetry based on conventional cytogenetic
      technique (dicentrics) has been unsuccessful for various groups (rehabilitation
      workers, evacuees, inhabitants of contaminated areas) sampled long time after the
      Chernobyl accident. The possible reasons of the failure are analysed. The
      original results of multiaberration cell yield observed in different cohorts of
      the Chernobyl victims are presented. The problems related to the phenomena are
      discussed.

PMID- 11252236
TI  - [Mutagenesis in Muridae from regions with increased radiation level].
AB  - Genetic monitoring of wild populations of mouse-like rodents has been carried out
      since 1992 in areas with the increased radioactivity in the south of the Bryansk
      region. The radioactive background ranged from 0.20 to 2.20 mkGy/h. Over 400
      rodents of different species have been examined. Bank vole constituted more than
      a half of the examined animals. The genetic effect of radiation was estimated by
      the frequency of micronuclei in normochromatic erythrocytes of peripheral blood
      and by the frequency of abnormal sperm heads. In house mice the frequency of
      reciprocal translocations and the level of embryo mortality were studied in the
      progeny of the caught male mice mated with intact laboratory females. The data
      obtained demonstrate that the yield of induced genetic disorders by all tests was
      relatively low and only in a few cases the frequency of disturbances tended to
      increase with an increase in the level of radionuclide contamination in the
      examined areas.

PMID- 11252235
TI  - [Cytogenetic studies of blood lymphocytes of cosmonauts after long-ter, space
      flights].
AB  - An analysis was performed of unstable chromosomal aberrations in peripheral blood
      of 36 cosmonauts after long-term space missions on "Mir" orbital station. 25
      cosmonauts were examined before their flights to score spontaneous yields of
      cytogenetical damage. In all cases the doses absorbed by crews during space
      flights did not exceed permissible levels of irradiation, adopted for cosmonauts.
      The frequencies of chromosomal-type aberrations after space missions were found
      to increase significantly compared to the pre-flight levels. The yields of
      dicentrics and centric rings on the average were as high as 0.12 +/- 0.02 and
      0.47 +/- 0.06% before and after the 1st flight, 0.18 +/- 0.05 and 0.71 +/- 0.11%
      before and after the 2nd flight respectively. During the inter-flight periods,
      usually lasted 1.5-2 years, the yields of chromosome damage lowered, but did not
      reach their spontaneous values. After each next flight the yields of chromosome
      aberrations increased again. The cytogenetical damage detected in cosmonauts'
      peripheral blood lymphocytes after chronic action of low doses of space radiation
      points out a possible increase in risks of stochastic effects in distant future
      for crews after long-term space missions.

PMID- 11252237
TI  - [Radiation-population monitoring of Pinus sylvestris L. in the zone of the
      Chernobyl power plant].
AB  - Cytogenetic and genetic effects in populations of Pinus sylvestris L. suffered
      wiak, average, strong and sublethal radiation damage after the Chernobyl accident
      in 1986 were studied. The absorbed dozes for trees in these plantings were from
      0.1 up to 20 Gy. It was shown that the amount of cells with chromosome
      aberrations in sprouts of seeds of a crop of 1993, are comparable with effects
      marked at once after accident in 1986. In 1997 and in 1998 the amount of cells
      with chromosome aberrations in sprouts of seeds in majority inspected plantings
      decreased to control values. The effect of adaptation was detected, when seeds of
      Pinus sylvestris L., gathered in 1997 from inspected trees, were exposed to
      additional 4 Gy gamma-radiation.

PMID- 11252238
TI  - [Current problems of estimation of genetic risk of human exposure to radiation].
AB  - The methodology of assessing the genetic risk of radiation exposure is based on
      the concept of "hitting the target" in development of which N.V. Timofeeff
      Ressovsky has played and important role. To predict genetic risk posed by
      irradiation, the UN Scientific Committee on the Effects of Atomic Radiation
      (UNSCEAR) has worked out direct and indirect methods of assessment,
      extrapolational, integral and populational criteria of risk analysis that
      together permit calculating the risk from human exposure on the basis of data
      obtained for mice. Laboratory mice are the main objects in studying radiation
      mutagenesis due to the fact that the data on the frequency of radiation-induced
      human mutations are rather scarce. The method of doubling dose based on the
      determination of a dose doubling the level of natural mutational process in
      humans is the main one used to predict the genetic risk. The evolution of views
      about the genetics risk of human exposure to radiation for last 40 years is
      considered. Till 1972 the main model for assessing the genetic risk was the
      "human/mouse" model (the use of data on the spontaneous human variability and
      data on the frequency of induced mutations in mice). In the period form 1972 till
      1994 the "mouse/mouse" model was intensively elaborated in many laboratories.
      This model was also used in this period by UNSCEAR experts to analyze the genetic
      risk from human irradiation. Recent achievements associated with the study of the
      molecular nature of many hereditary human diseases as well as the criticism of
      number fundamental principles of the "mouse/mouse" model for estimating the
      genetic risk on a new basis. The estimates of risk for the different classes of
      genetic diseases have been obtained using the doubling-dose method. The estimate
      of doubling dose used in the calculations is 1 Gy for low dose/chronic low-LET
      radiation conditions.

PMID- 11252239
TI  - Biomedical Engineering Society 2000 Annual Fall Meeting. 12-14 October 2000.
      Abstracts.

PMID- 11252241
TI  - Reimbursement options for WOC(ET) nurses in home health. Fact sheet produced by
      Regulatory/Reimbursement Subcommittee for WOCN.

PMID- 11252240
TI  - Proceedings of the Consensus Conference on Premalignant Lesions in the Genito
      urinary tract. Stockholm, Sweden, June 8-9, 2000.

PMID- 11252242
TI  - ESTRO-MITRE 2000. Brussels, Belgium, 10-11 December 2000. Abstracts.

PMID- 11252243
TI  - US FDA advisory committee recommends approval of tacrolimus ointment.

PMID- 11252244
TI  - Update on drugs.

PMID- 11252245
TI  - [Acute myocardial infarction in nocturnal paroxysmal hemoglobinuria].
AB  - The case of a 62-year-old diabetic and smoker male who was under study in another
      hospital due to anemia, thrombopenia and hematuria of several months of evolution
      is presented. The patient was admitted to the coronary unit for an acute
      extensive transmural myocardial infarction and treated with t-PA. A few hours
      later the patient presented hematuric urine, a decrease in hemoglobin and
      platelets and acute renal insufficiency. Hematologic study confirmed the
      diagnosis of paroxystic nocturnal hemoglobinuria. The evolution of the patient
      was poor despite intensive medical treatment requiring hemodialysis. The patient
      presented cardiac tamponade and died. The role of hematologic disease in acute
      myocardial infarction and the treatment and evolution of the coronary syndrome in
      the context of the disease are discussed.

PMID- 11252246
TI  - Force-feedback during human walking.

PMID- 11252247
TI  - Brain repair--new avenues to an eternal dream?

PMID- 11252248
TI  - Embryo jigsaws.

PMID- 11252249
TI  - SNPs, lonkage disequilibrium, human genetic variation and Native American
      culture.

PMID- 11252250
TI  - Vaccinating women against premature death: summary of an International Workshop,
      Helsinki, Finland, 10.01.2000.

PMID- 11252251
TI  - College on Problems of Drug Dependence. 62nd Annual Scientific Meeting. June 17
      22, 2000. San Juan, Puerto Rico. Abstracts.

PMID- 11252252
TI  - Putative integral membrane SRP receptors.

PMID- 11252253
TI  - TRITON: graphic software for rational engineering of enzymes.
AB  - Engineering of the catalytic properties of enzymes requires knowledge about amino
      acid residues interacting with the transition state of the substrate. TRITON is a
      graphic software package for modelling enzymatic reactions for the analysis of
      essential interactions between the enzyme and its substrate and for in silico
      construction of protein mutants. The reactions are modelled using semi-empirical
      quantum-mechanic methods and the protein mutants are constructed by homology
      modelling. The users are guided through the calculation and data analysis by
      wizards.

PMID- 11252254
TI  - Antimicrobial activity against obligate intracellular bacteria.

PMID- 11252256
TI  - Vessel content debate revisited.

PMID- 11252257
TI  - One of nature's most innovative laboratories.

PMID- 11252255
TI  - Biofilms adhere to stay.

PMID- 11252258
TI  - Fructan 2000.

PMID- 11252259
TI  - Cannabinoids: don't use them without a medical prescription!

PMID- 11252260
TI  - Cyclosporin A and free radical generation.

PMID- 11252261
TI  - The troubled story of tachykinins and neurokinins: an update.

PMID- 11252262
TI  - [Clinico-biologic and molecular study of mucopolysaccharidosis in central and
      southern Tunisia].

PMID- 11252264
TI  - Biomedical microdevices and nanotechnology.

PMID- 11252263
TI  - Accessing biomolecular diversity: the challenge.

PMID- 11252265
TI  - What you see is what you think--or is it?

PMID- 11252266
TI  - Recent advances in neuralstem cell technologies.

PMID- 11252267
TI  - Reorganization of the human central nervous system.
AB  - The key strategies on which the discovery of the functional organization of the
      central nervous system (CNS) under physiologic and pathophysiologic conditions
      have been based included (1) our measurements of phase and frequency coordination
      between the firings of alpha- and gamma-motoneurons and secondary muscle spindle
      afferents in the human spinal cord, (2) knowledge on CNS reorganization derived
      upon the improvement of the functions of the lesioned CNS in our patients in the
      short-term memory and the long-term memory (reorganization), and (3) the dynamic
      pattern approach for re-learning rhythmic coordinated behavior. The theory of
      self-organization and pattern formation in nonequilibrium systems is explicitly
      related to our measurements of the natural firing patterns of sets of identified
      single neurons in the human spinal premotor network and re-learned coordinated
      movements following spinal cord and brain lesions. Therapy induced cell
      proliferation, and maybe, neurogenesis seem to contribute to the host of
      structural changes during the process of re-learning of the lesioned CNS. So far,
      coordinated functions like movements could substantially be improved in every of
      the more than 100 patients with a CNS lesion by applying coordination dynamic
      therapy. As suggested by the data of our patients on re-learning, the human CNS
      seems to have a second integrative strategy for learning, re-learning, storing
      and recalling, which makes an essential contribution of the functional plasticity
      following a CNS lesion. A method has been developed by us for the simultaneous
      recording with wire electrodes of extracellular action potentials from single
      human afferent and efferent nerve fibres of undamaged sacral nerve roots. A
      classification scheme of the nerve fibres in the human peripheral nervous system
      (PNS) could be set up in which the individual classes of nerve fibres are
      characterized by group conduction velocities and group nerve fibre diameters.
      Natural impulse patterns of several identified single afferent and efferent nerve
      fibres (motoneuron axons) were extracted from multi-unit impulse patterns, and
      human CNS functions could be analyzed under physiologic and pathophysiologic
      conditions. With our discovery of premotor spinal oscillators it became possible
      to judge upon CNS neuronal network organization based on the firing patterns of
      these spinal oscillators and their driving afferents. Since motoneurons fire
      occasionally for low activation and oscillatory for high activation, the coherent
      organization of subnetworks to generate macroscopic function is very complex and
      for the time being, may be best described by the theory of coordination dynamics.
      Since oscillatory firing has also been observed by us in single motor unit firing
      patterns measured electromyographically, it seems possible to follow up
      therapeutic intervention in patients with spinal cord and brain lesions not only
      based on the activity levels and phases of motor programs during locomotion but
      also based on the physiologic and pathophysiologic firing patterns and
      recruitment of spinal oscillators. The improvement of the coordination dynamics
      of the CNS can be partly measured directly by rhythmicity upon the patient
      performing rhythmic movements coordinated up to milliseconds. Since rhythmic
      dynamic, coordinated, stereotyped movements are mainly located in the spinal cord
      and only little supraspinal drive is necessary to initiate, maintain, and
      terminate them, rhythmic, dynamic, coordinated movements were used in therapy to
      enforce reorganization of the lesioned CNS by improving the self-organization and
      relative coordination of spinal oscillators (and their interactions with
      occasionally firing motoneurons) which became pathologic in their firing
      following CNS lesion. Paraparetic, tetraparetic spinal cord and brain-lesioned
      patients re-learned running and other movements by an oscillator formation and
      coordination dynamic therapy. Our development in neurorehabilitation is in
      accordance with those of theoretical and computational neurosciences which deal
      with the self-organization of neuronal networks. In particular, jumping on a
      springboard 'in-phase' and in 'anti-phase' to re-learn phase relations of
      oscillator coupling can be understood in the framework of the Haken-Kelso-Bunz
      coordination dynamic model. By introducing broken symmetry, intention, learning
      and spasticity in the landscape of the potential function of the integrated CNS
      activity, the change in self-organization becomes understandable. Movement
      patterns re-learned by oscillator formation and coordination dynamic therapy
      evolve from reorganization and regeneration of the lesioned CNS by cooperative
      and competitive interplay between intrinsic coordination dynamics, extrinsic
      therapy related inputs with physiologic re-afferent input, including intention,
      motivation, supervised learning, interpersonal coordination, and genetic
      constraints including neurogenesis. (ABSTRACT TRUNCATED)

PMID- 11252268
TI  - Photo quiz. Disseminated Pneumocystitis carinii infection.

PMID- 11252269
TI  - What price an idea?

PMID- 11252270
TI  - Walmsley's web watch.

PMID- 11252271
TI  - Enhancing caregiver outcomes in palliative care.
AB  - BACKGROUND: Families are increasingly replacing skilled health care workers in
      the delivery of unfamiliar complex care to their relatives with cancer, despite
      other obligations and responsibilities that characterize their lives. METHODS:
      The authors review the needs of cancer caregivers and describe intervention
      strategies not only presented in the literature, but also implemented in their
      own program of research to address those needs during the palliative phase of
      cancer. RESULTS: Research suggests that developing interventions that teach
      caregivers to become proficient in the physical and psychological aspects of
      patient care will benefit both patients and caregivers. CONCLUSIONS: Despite the
      fact that a cancer diagnosis can cause major changes in family roles and
      functioning,as well as increased responsibility for complex care being absorbed
      by family caregivers, data supporting the effectiveness of caregiver
      interventions have been limited.

PMID- 11252272
TI  - 20th International Symposium on Intensive Care and Emergency Medicine. Brussels,
      21-24 March 2000. Abstracts.

PMID- 11252273
TI  - ISRO-ICRO 2001. 6th International Congress of Radiation Oncology. 30 January-2
      February 2001. Melbourne, Australia. Abstracts.

PMID- 11252274
TI  - Five new species of coccidia (Apicomplexa: Eimeriidae) from Madagascan chameleons
      (Sauria: Chamaeleonidae).
AB  - Coprological examination of 19 Madagascan chameleons of the genera Furcifer and
      Brookesia revealed the presence of five new coccidian species. Isospora brygooi
      n. sp. from Furcifer pardalis has spherical to subspherical oocysts with a
      slightly pitted wall, 20.7 (17-24.5) x 19.3 (16-23) microm and broadly
      ellipsoidal sporocysts, 12.2 (11.5-13) x 8.1 (8-8.5) microm, with Stieda and
      substieda bodies. Oocysts of Eimeria glawi n. sp. from Furcifer pardalis are
      cylindrical to ellipsoidal, 27.7 (26-29.5) x 18.4 (17-19) microm, with
      ellipsoidal sporocysts, 7.3 (6.5-8) x 5.2 (5-5.5) microm. E. vencesi n. sp.
      described from F. pardalis has spherical to subspherical oocysts, 14.3 (13-15.5)
      x 13.0 (12-13) microm, with small granules, one to three globular polar granules
      and ellipsoidal sporocysts, 7.3 (6.5-8) x 5.2 (5-5.5) microm. E. worthi n. sp.,
      described from Furcifer oustaleti has spherical oocysts, 17.9 (17.5-19.0) x 15.0
      (14.5-16.0) microm without a polar granule and ellipsoidal to cylindroidal
      sporocysts, 8.2 (7.0-9.5) x 5.8 (5.0-6.5) microm. Oocysts of E. brookesiae n. sp.
      from Brookesia decaryi are cylindrical, 25.6 (23-27) x 15.0 (13-16) microm with
      ellipsoidal sporocysts, 10.1 (9-11) x 6.9 (6-7) microm. Endogenous development of
      E. vencesi is confined to the intestine, while that of E. glawi occurs in the
      gall-bladder.

PMID- 11252275
TI  - Ceratomyxa seriolae n. sp. and C. buri n. sp. (Myxozoa: Myxosporea) from the gall
      bladder of cultured yellowtail Seriola quinqueradiata.
AB  - Ceratomyxa seriolae n. sp. and C. buri n. sp. (Myxozoa: Myxosporea) were found in
      the gall-bladder of cultured yellowtail Seriola quinqueradiata Temminck &
      Schlegel (Carangidae) in Japan. Mature spores of C. seriolae n. sp. were elongate
      and 6.5 (6.0-7.5) microm long and 33.7 (28.0-41.5) microm thick. Disporous
      plasmodia of C. seriolae n. sp., 40-100 microm in size, were amoeboid to
      spherical. C. buri n. sp. were elliptical with a flattened posterior end. 6.5
      (5.5-7.5) microm long and 14.3 (11.0-16.5) microm thick. Spherical plasmodia of
      C. buri n. sp., 15-20 microm in diameter, were disporous. In periodical sampling
      of yellowtail bile from August, 1999 to February, 2000, the two new species of
      Ceratomyxa, as well as Myxobolus spirosulcatus Maeno, Sorimachi, Ogawa & Kearn
      1995, first appeared in October, and the prevalences were very variable (20-100%)
      during the study period.

PMID- 11252276
TI  - Longidorus cretensis n. sp. (Nematoda: Longidoridae) from a vineyard infected
      with a foliar 'yellow mosaic' on Crete, Greece.
AB  - A description is provided of Longidorus cretensis n. sp., a bisexual species
      associated with grapevines in Crete, Greece. The species is characterised by a
      body length of 6.3-8.7 mm, head flattened anteriorly and continuous with the body
      profile, amphids pocket-shaped and not bilobed, a posteriorly situated guide
      ring, posteriorly situated oesophageal glands, and a tail bluntly rounded to
      hemispherical. Xiphinema index was present throughout the vineyard, but L.
      cretensis n. sp. occurred only in an area where the grapevine foliage exhibited a
      'yellow mosaic' disease, and in association with X. pachtaicum from the
      rhizosphere of an olive tree growing adjacent to the vineyard. Nematode
      transmitted virus was not recovered from weed species growing in the vicinity of
      the olive tree, or by bait-testing soil collected from the rhizosphere of the
      tree. Population densities of L. cretensis n. sp. were similar under olive and
      grapevine, but twice as many adult specimens were recovered from soil samples
      collected in the vineyard. Three quarters of L. cretensis specimens were present
      at 21-40 cm depth under olive, whereas a similar proportion of the population was
      equally distributed under grapevine at 21-40 cm and 41-60 cm depths.

PMID- 11252278
TI  - [From some Hymenolepididae (Cestoda)of Alaskan Charadrii birds, where
      Nadejdolepis bealli n.sp., is a parasite of Calidris alpina].
AB  - Nadejdolepis bealli n. sp. a parasite from Calidris alpina in Alaska (USA), is
      described and illustrated. It is 3-4 cm long and has: rostral nitiduloid hooks 95
      96 microm long, with the blade a little longer than the handle; three testes in a
      symmetrical triangle; a cirrus-sac 175 microm long, not crossing the median line;
      a cirrus borne on an unarmed basal bulb, 25 microm long when evaginated, and
      armed with numerous, compact and very thin spines 1 microm long; a short (25
      microm) membranous and tubular vagina with neither a sclerotinoid section nor a
      sphincter; and a pyriform seminal receptacle. The species is differentiated from
      the other species of the genus with rostral hooks of comparable length by the
      configuration of the male and female genital ducts; they have no equivalent
      particularly in the shortness of the evaginated cirrus and the type of spines
      with which it is armed. Mention is also made of the presence of Nadejdolepis
      paranitidulans (Golikova, 1959) and Wardium amphitricha (Rudolphi, 1819) from the
      same host in Alaska.

PMID- 11252277
TI  - Redescription of Gyrodactylus teuchis Lautraite, Blanc, Thiery, Daniel &
      Vigneulle, 1999 (Monogenea: Gyrodactylidae); a species identified by ribosomal
      RNA sequence.
AB  - Molecular and morphological features of Gyrodactylus specimens from Oncorhynchus
      mykiss, Salmo trutta and Salmo salar were examined. Sequences from variable
      region V4 of the small subunit ribosomal RNA gene and the ribosomal RNA internal
      transcribed spacers, produced by the FRS Marine Laboratory, revealed that these
      were not the same as other well-characterised Gyrodactylus that are common on
      European salmonids and were in fact a distinct species. Initial morphological
      examination of the opisthaptor indicated that this species very closely resembles
      G. salaris Malmberg, 1957. More detailed analysis revealed differences in the
      shape of the marginal hook sickle of these two species and thus Gyrodactylus
      teuchis Lautraite, Blanc, Thiery, Daniel & Vigneulle, 1999 was erected. Analysis
      of the ribosomal RNA gene or spacer sequences remains the most reliable method of
      identifying this species. This is believed to be the first record of a
      Gyrodactylus species identified first from molecular data and confirmed by
      morphological examination; previous molecular analyses had provided alternative
      methods for identifying species that had already been described using
      morphological characters.

PMID- 11252279
TI  - Phylogeny of the Acanthocephala based on morphological characters.
AB  - Only four previous studies of relationships among acanthocephalans have included
      cladistic analyses, and knowledge of the phylogeny of the group has not kept pace
      with that of other taxa. The purpose of this study is to provide a more
      comprehensive analysis of the phylogenetic relationships among members of the
      phylum Acanthocephala using morphological characters. The most appropriate
      outgroups are those that share a common early cell-cleavage pattern (polar
      placement of centrioles), such as the Rotifera, rather than the Priapulida
      (meridional placement of centrioles) to provide character polarity based on
      common ancestry rather than a general similarity likely due to convergence of
      body shapes. The phylogeny of 22 species of the Acanthocephala was evaluated
      based on 138 binary and multistate characters derived from comparative
      morphological and ontogenetic studies. Three assumptions of cement gland
      structure were tested: (i) the plesiomorphic type of cement glands in the
      Rotifera, as the sister group, is undetermined; (ii) non-syncytial cement glands
      are plesiomorphic; and (iii) syncytial cement glands are plesiomorphic. The
      results were used to test an early move of Tegorhynchus pectinarius to
      Koronacantha and to evaluate the relationship between Tegorhynchus and
      Illiosentis. Analysis of the data-set for each of these assumptions of cement
      gland structure produced the same single most parsimonious tree topology. Using
      Assumptions i and ii for the cement glands, the trees were the same length
      (length = 404 steps, CI = 0.545, CIX = 0.517, HI = 0.455, HIX = 0.483, RI =
      0.670, RC = 0.365). Using Assumption iii, the tree was three steps longer (length
      = 408 steps, CI = 0.539, CIX = 0.512, HI = 0.461, HIX = 0.488, RI = 0.665, RC =
      0.359). The tree indicates that the Palaeacanthocephala and Eoacanthocephala both
      are monophyletic and are sister taxa. The members of the Archiacanthocephala are
      basal to the other two clades, but do not themselves form a clade. The results
      provide strong support for the Palaeacanthocephala and the Eoacanthocephala and
      the hypothesis that the Eoacanthocephala is the most primitive group is not
      supported. Little support for the Archiacanthocephala as a monophyletic group was
      provided by the analysis. Support is provided for the recognition of Tegorhynchus
      and Illiosentis as distinct taxa, as well as the transfer of T. pectinarius to
      Koronacantha.

PMID- 11252280
TI  - Health and education of children with albinism in Zimbabwe.
AB  - Albinism is a relatively common genetic condition in Zimbabwe, a tropical country
      in southern Africa. Those affected have little pigment in their hair, skin or
      eyes, in sharp contrast to the normal dark pigmentation. This article describes
      the responses to a self-report questionnaire covering health, social and
      educational aspects completed by 138 schoolchildren with albinism living in rural
      areas of Zimbabwe. They reported persistent skin and a myriad of eye problems.
      Relationships between siblings appeared good, although problems of antagonism,
      avoidance and fear were encountered among strangers. Knowledge about albinism was
      patchy; pupils were keen to be better informed. This research highlights the need
      for widespread dissemination of accurate information about the genetics and
      health management of albinism to counter the many myths and misconceptions
      surrounding this condition. A management programme to promote the health and
      education of these children in southern Africa is proposed. In conclusion, this
      study indicated that pupils with albinism could participate in mainstream
      education, with appropriate intervention to help them manage the problems
      associated with their low vision and sensitive skins.

PMID- 11252281
TI  - Gender and race differences in the predictors of daily health practices among
      older adults.
AB  - Preventive health behaviors are crucial for older adults' well-being. This study
      examined the factors that influence the practice of positive daily health
      behaviors over time in a sample of older adults (N = 1266) and investigated
      whether explanatory factors differ by health behavior, gender or race. Physical
      activity, weight maintenance, smoking, alcohol consumption and sleep patterns
      were examined as dependent variables. Independent variables included demographic
      characteristics, baseline health behavior, health status variables, psychological
      factors and social network characteristics. Results indicate that age and health
      status are important predictors of preventive health behaviors. However, the
      factors that predict preventive health behaviors vary by behavior, gender and
      race. The independent variables included in this study were most successful in
      explaining cigarette smoking and weight maintenance, and least successful in
      explaining amount of sleep. In addition, results suggest that social network
      variables are particularly influential for women's health behaviors, while health
      status is more influential among men. Greater education predicts better health
      behaviors among whites, while formal social integration seems particularly
      important for the health behaviors of older black women. These results indicate
      that examining older adults' health behaviors by race and gender leads to a
      fuller understanding of these behaviors.

PMID- 11252282
TI  - Investigating student nurses' constructions of health promotion in nursing
      education.
AB  - This article describes student nurses' constructions of health promotion and the
      change of these constructions during their nursing education in two Finnish
      polytechnics. The data consisted of essays written by the 19 student nurses
      before they began their nursing education in 1997 and of stimulated recall
      interviews with the same students during the second year of their education in
      1998. The data were analyzed by using thematic analysis. During the first study
      year, 13 students' constructions of health promotion changed. Six students had
      initially broad constructions of health promotion and their constructions
      remained unchanged. Four basic changes were found in the students' constructions:
      (1) the emphasis shifted from physical to multidimensional health promotion, (2)
      health promotion became more concrete and contextual, (3) the conception of
      perfect health became more permissive and relative, and (4) the interpretation of
      health promotion shifted from performing towards being there for the patient.
      These results may indicate that student nurses in Finnish polytechnics were
      attempting to adopt the empowerment approach to health promotion for their
      constructions. Moreover, the results represent a major challenge concerning
      nursing education and health promotion learning from the constructivistic
      approach to knowledge building.

PMID- 11252283
TI  - Smoking cessation between teenage years and adulthood.
AB  - Most smokers begin smoking in adolescence. It is less well known how young people
      quit smoking and the factors that are associated with this process. A 15-year
      follow-up study on the North Karelia Youth Project has made it possible to assess
      these factors using a longitudinal study design. The project began in 1978 with
      students in Grade 7 of junior high school (age 13 years) and concluded in 1980
      when the students reached Grade 9 (age 15 years). The follow-up study included
      four additional surveys. The present analyses are based on the data collected at
      ages 15, 21 and 28. The original sample comprised 903 students and the response
      rate of the last survey was 71%. A quarter (26%) of daily smokers and about half
      (46%) of occasional smokers at age of 15 had quit by the age of 28. The cessation
      rate was higher among females than males (P = 0.006). The cessation rate was
      higher among married (P = 0.015), employed (P = 0.01) and white-collar workers (P
      = 0.006). Cessation was less prevalent among those who had friends (P < 0.001)
      and family (P = 0.012) members who smoked. The cessation rate was lower among
      those who consumed fatty milk (P = 0.050), had less leisure-time physical
      activity (P = 0.032) and consumed more alcohol (P < 0.001). One-third of all
      teenage smokers stop smoking before the age of 28, averaging a 2.3% annual
      decline. Cessation is greater among occasional than daily smokers and greater
      overall among females.

PMID- 11252284
TI  - How did Project Northland reduce alcohol use among young adolescents? Analysis of
      mediating variables.
AB  - Project Northland is a randomized trial designed to create, implement and
      evaluate multilevel, community-wide strategies to prevent alcohol use among
      adolescents. This paper will focus on the mediating outcomes of the early
      adolescent phase of Project Northland when the students in the study cohort were
      in Grades 6-8. The project was conducted in 24 school districts and adjacent
      communities in northeastern Minnesota. The intervention consisted of social
      behavioral curricula in schools, peer leadership activities, parental involvement
      and education, and community-wide activities. At the end of 3 years of
      intervention, significantly fewer students in the intervention school districts
      reported alcohol use than students in the reference districts. Mediation analyses
      were conducted to investigate if the intervention's effects on mediating
      variables could explain the reduction in alcohol use. Important mediators of
      Project Northland's effect on alcohol use were: (1) peer influence to use,
      including normative estimates, (2) functional meanings of alcohol use, (3)
      attitudes and behaviors associated with alcohol and drug problems like stimulus
      seeking, rule violations and bad judgement, and (4) parent-child alcohol-related
      communication around alcohol use. In addition, among those who did not use
      alcohol at baseline, self-efficacy to refuse offers of alcohol was a significant
      mediator.

PMID- 11252285
TI  - PrePare: a program of enhanced prenatal services within health-maintenance
      organization settings.
AB  - This paper presents the conceptual framework and implementation strategies of a
      relationship-focused behavioral intervention for pregnant women and their
      families. The program, PrePare ('Prenatal Parenting'), was designed as a prenatal
      precursor to the pediatric health care model, Healthy Steps. PrePare includes
      preventive intervention elements that address parents' universal concerns about
      pregnancy and parenthood, as well as specific activities to support optimum
      pregnancy health and reduce high-risk behaviors. As described here, the program
      is embedded within a large not-for-profit health-maintenance organization (HMO).
      Delivery of the prenatal component is carried out by Healthy Steps
      interventionists through three home visits and telephone follow-up during
      mothers' second and third trimesters of pregnancy. An evaluation of program
      outcomes is underway. The design compares three groups of families, those who
      receive PrePare followed by Healthy Steps, Healthy Steps alone and a usual HMO
      practice comparison. It is hypothesized that initiating expanded services during
      the prenatal period will lead to increases in reported patient satisfaction,
      provider satisfaction and organizational efficiency within the health care
      delivery system.

PMID- 11252286
TI  - Effects of persuasive message order on coping with breast cancer information.
AB  - The current study explored the impact of varying the order of message components
      on coping with breast cancer information. In a 2 x 2 x 2 factorial design, threat
      information, coping information and order of information were manipulated.
      College students read persuasive essays that varied in emphasis on threat of
      developing breast cancer and effectiveness of breast self-examination (BSE) in
      averting the threat of cancer. Participants who read the high-threat message
      reported higher intentions to perform BSE, more rational problem solving and more
      hopelessness than did those who read a low-threat message. The coping information
      messages produced a similar pattern of results. In addition, those who read the
      high-coping message reported less fatalism than did participants who read the low
      coping message. When threat information was presented first, the high-threat
      message led to less hopelessness and reliance on religious faith than when the
      coping information was presented first. These results demonstrate the threatening
      health information energizes one to act in both adaptive and maladaptive ways,
      and that coping information decreases the tendency to respond maladaptively to
      the health threat. They also suggest that the order of presentation of the
      information may affect the extent to which people respond adaptively.

PMID- 11252287
TI  - Evaluation of a comprehensive school-based AIDS education programme in rural
      Masaka, Uganda.
AB  - A 19 activity extracurricular school-based AIDS education programme lasting 1
      year was conducted in rural southwestern Uganda using specially trained teachers,
      and was evaluated using mutually supportive quantitative and qualitative methods.
      In total, 1274 students from 20 intervention schools and 803 students from 11
      control schools completed questionnaires at baseline, and their classes were
      followed up. In addition, 93 students from five of the intervention schools
      participated in 12 focus group discussions. The programme had very little effect-
      seven of the nine key questionnaire variables showed no significant increase in
      score after the intervention. Data from the focus group discussions suggest that
      the programme was incompletely implemented, and that key activities such as
      condoms and the role-play exercises were covered only very superficially. The
      main reasons for this were a shortage of classroom time, as well as teachers'
      fear of controversy and the unfamiliar. We conclude that large-scale
      comprehensive school-based AIDS education programmes in sub-Saharan Africa may be
      more completely implemented if they are fully incorporated into national
      curricula and examined as part of life-skills education. This would require
      teachers to be trained in participatory teaching methods while still at training
      college.

PMID- 11252288
TI  - Vaginal thrush: perceptions and experiences of women of south Asian descent.
AB  - It is estimated that 75% of all women will, at some time in their lives,
      experience at least one episode of vaginal thrush. This paper reports the
      perceptions and experiences of women of South Asian descent living in England,
      who were suffering or had suffered from thrush. The paper draws upon data
      collected during 20 semi-structured interviews. The women reported that thrush
      sometimes had a considerable impact on their lives, making some of them feel
      'dirty', embarrassed, depressed and stigmatized. Some women delayed seeking
      professional help even if they had access to a female General Practitioner.
      Access to professional care was sometimes hampered by language barriers, but more
      often by structural factors of gender and social class. Although almost all the
      women came originally from Gujarat (or had parents who were born in Gujarat),
      they reported a wide range of experiences. Since vaginal thrush causes much
      distress and since it is often preventable, the findings presented here have
      implications for clinical practice. The paper concludes with suggestions for
      future developments.

PMID- 11252289
TI  - Rett syndrome: review of biological abnormalities.
AB  - The Rett syndrome (RS) is a peculiar, sporadic, atrophic disorder, almost
      entirely confined to females. After the first six months of life there is
      developmental slowing with reduced communication and head growth for about one
      year. This is followed by a rapid destructive stage with severe dementia and loss
      of hand skills (with frequent hand wringing), apraxia and ataxia, autistic
      features and irregular breathing with hyperventilation. Seizures often supervene.
      Subsequently there is some stabilization in a pseudo-stationary stage during the
      preschool to school years, associated with more emotional contact but also
      abnormalities of the autonomic and skeletal systems. After the age of 15-20
      years, a late motor deterioration occurs with dystonia and frequent spasticity
      but seizures become milder. RS has generally been considered an X-linked disorder
      in which affected females represent a new mutation, with male lethality. Linkage
      studies suggested a critical region at Xq28. In 1999, mutations in the gene MECP2
      encoding X-linked methyl cytosine-binding protein 2 (MeCP2) were found in a
      proportion of Rett girls. This protein can bind methylated DNA. Analyses are
      leading to much further investigation of mutants and their effects on genes.
      Neuropathological and electrophysiological studies of RS are described.
      Description of neurometabolic factors includes reduced levels of dopamine,
      serotonin, noradrenaline and choline acetyltransferase (ChAT) in brain, also
      estimation of nerve growth factors, endorphin, substance P, glutamate and other
      amino acids and their receptor levels. The results of neuroimaging are surveyed,
      including volumetric magnetic resonance imaging (MRI) and positron emission
      tomography (PET).

PMID- 11252290
TI  - CNS injury and helmets.

PMID- 11252291
TI  - A systematic review of the use of triptans in acute migraine.
AB  - OBJECTIVE: A systematic review of the literature was undertaken, to consolidate
      evidence concerning the efficacy and safety of triptans currently available in
      Canada (sumatriptan, rizatriptan, naratriptan, zolmitriptan), and to provide
      guidelines for selection of a triptan. METHODS: Data from published, randomized,
      placebo-controlled trials were pooled and a combined number needed to treat (NNT)
      and number needed to harm (NNH) was generated for each triptan. Direct
      comparative trials of triptans were also examined. RESULTS: The lowest NNT for
      headache response/pain-free at one/two hours is observed with subcutaneous
      sumatriptan. Among the oral formulations, the lowest NNT is observed with
      rizatriptan and the highest NNT with naratriptan. The lowest NNH is observed with
      subcutaneous sumatriptan. CONCLUSIONS: Triptans are relatively safe and effective
      medications for acute migraine attacks. However, differences among them are
      relatively small. Considerations in selecting a triptan include individual
      patient response/tolerance, characteristics of the attacks, relief of associated
      symptoms, consistency of response, headache recurrence, delivery systems and
      patient preference.

PMID- 11252292
TI  - Commentary on epilepsy surgery in Canada.

PMID- 11252293
TI  - Head injuries in skiers and snowboarders in British Columbia.
AB  - BACKGROUND: At the Vancouver General Hospital Neurosurgical Service there have
      been a significant number of seriously brain injured snowboarders, seemingly out
      of proportion to the number of skiers. The purpose of this study was to determine
      whether snowboarders suffered more serious head injuries than skiers in the
      Vancouver catchment area. METHODS: The British Columbia Trauma Registry was
      searched for patients incurring head injuries while skiing or snowboarding on
      British Columbia mountains during the period from January 1992 to December 1997.
      Patients were included if they were admitted to hospital and underwent
      neurosurgical consultation. RESULTS: A total of 40 skiers and 14 snowboarders met
      the above criteria. Of the skiers, 15% sustained a severe head injury by Glasgow
      Coma Score, another 30% sustaining moderate head injuries, while 29% of
      snowboarders had a severe injury and 36% a moderate injury. A concussion was
      present in 60% of the skiers and 21% of the snowboarders. Snowboarders suffered
      an intracranial hemorrhage in 71% of the cases compared to 28% of the skiers. A
      craniotomy was performed acutely in 10% of skiers and in 29% of snowboarders.
      Three deaths occurred as a direct result of head injury, one while snowboarding.
      All but one of the surviving skiers were able to return home, whereas four of 13
      surviving snowboarders required additional inpatient rehabilitation or transfer
      to another acute hospital for ongoing care. CONCLUSIONS: Snowboarders suffer more
      significant head injuries compared to skiers in this series and are much more
      likely than skiers to require an intracranial procedure. In our opinion, this
      indicates that additional safety measures, in particular the use of mandatory
      helmets, should be considered by ski areas and their patrons.

PMID- 11252294
TI  - Screening for cerebellopontine angle tumours: conventional MRI vs T2 fast spin
      echo MRI.
AB  - BACKGROUND: Unilateral audiovestibular symptoms are commonly seen in clinical
      practice and are rarely caused by retrocochlear pathology. However, clinicians
      are often required to rule out potentially serious causes of these unilateral
      symptoms. Gadolinium enhanced magnetic resonance imaging (GdMRI) is the most
      accurate test for detecting small cerebellopontine angle lesions and also screens
      the adjacent CNS structures. Its main disadvantage is the cost of the procedure.
      METHODS: We studied 100 consecutive patients with both GdMRI and a newer MRI
      screening study utilizing unenhanced T2-weighted fast spin echo (fse) MRI.
      Acquired images were randomly assessed by a panel of three neuro-radiologists.
      RESULTS: We found that the screening (fse) MRI was as sensitive and specific when
      detecting cerebellopontine angle tumors. CONCLUSIONS: We conclude that T2
      weighted fse MRI is a safe and cost-effective alternative to GdMRI and offers
      better diagnostic utility when compared to auditory brain stem response (ABR) and
      CT scans.

PMID- 11252295
TI  - A founder mutation in French-Canadian families with X-linked hereditary
      neuropathy.
AB  - BACKGROUND: The aim of the present study was to identify the mutations in the
      connexin 32 gene in French-Canadian families with X-linked Charcot-Marie-Tooth
      disease (CMTX). METHODS: Molecular analysis was performed by nonisotopic single
      strand conformation polymorphism (SSCP) analysis and sequencing. Clinical
      evaluation was carried out according to the scale defined by the European
      Hereditary Motor and Sensory Neuropathy Consortium. RESULTS: In one family, the
      mutation Arg142Trp was located in the transmembrane domain III whereas, in four
      other families we identified a novel mutation (Ser26Trp) located in the
      transmembrane domain I of the connexin 32 gene. Haplotype analysis revealed that
      these four families are related and suggests a founder mutation. Sixteen patients
      from these four families were studied. As expected, all the affected males were
      more clinically affected than the females and all affected patients exhibited
      some electrophysiological characteristics of demyelination. CONCLUSION: Our study
      suggests that the Ser26Trp mutation may cause a primary demyelinating neuropathy
      that is not associated with a specific clinical phenotype. We also find evidence
      that the majority of kindreds share a common ancestor.

PMID- 11252296
TI  - Intraoperative fiber-optic endoscopy for ventricular catheter insertion.
AB  - OBJECTIVE: Ventricular catheter placement is a common neurosurgical procedure
      often resulting in inaccurate intraventricular positioning. We conducted a
      comparison of the accuracy of endoscopic and conventional ventricular catheter
      placement in adults. METHODS: A retrospective analysis of data was performed on
      37 consecutive patients undergoing ventriculo-peritoneal shunt (VPS) insertion
      with endoscopy and 40 randomly selected, unmatched patients undergoing VPS
      insertion without endoscopy, for the treatment of hydrocephalus of varied
      etiology. A grading system for catheter tip position was developed consisting of
      five intraventricular zones, V1 -V5, and three intraparenchymal zones, A, B, C.
      Zones V1 for the frontal approaches and V1 or V2 for the occipital approaches
      were the optimal catheter tip locations. Postoperative scans of each patient were
      used to grade the accuracy of ventricular catheter placement. RESULTS: Seventy
      six percent of all endoscopic ventricular catheters were in zone V1 and 100% were
      within zones V1-V3. No endoscopically inserted catheters were observed in zones
      V4, V5 or intraparenchymally. Thirty-eight percent of the conventionally placed
      catheters were in zone V1, 53% in zones V1-3 and 15% intraparenchymally. There
      was a statistically significant difference in the percentage of catheters in
      optimal location versus in any other location, favoring endoscopic guidance
      (p<0.001). CONCLUSION: We conclude that endoscopic ventricular catheter placement
      provides improved positioning accuracy than conventional techniques.

PMID- 11252298
TI  - Treatment costs for glioblastoma multiforme in Nova Scotia.
AB  - BACKGROUND: Glioblastoma Multiforme (GBM) is the most common and malignant brain
      tumor in adults. The median survival in patients harboring this neoplasm is 12
      months irrespective of any form of therapy. Health care costs of illnesses with
      high mortality rates, such as GBM, are of particular interest in times of
      constrained health care resources. No information regarding costs for the
      treatment of patients with GBM is available in Canada. The aim of this study was
      to conduct an analysis of the costs of treatment of GBM in Nova Scotia. METHODS:
      Patients with histologically proven GBM during a three year period (1996-1998) in
      Nova Scotia were included in the study. Analysis was based on hospital costs
      supplemented by data on additional medical services received following discharge
      for the primary intervention. RESULTS: The mean cost of medical care per patient
      from the time of diagnosis to death was $17,149. The highest costs were related
      to hospitalization with ward costs alone accounting for 48% of all costs.
      Radiotherapy costs were 25%, surgery costs were 16% and chemotherapy costs were
      7% of all costs. Costs for diagnostic procedures were 6% of the total costs.
      CONCLUSION: Our data reflect the costs and practice pattern in the treatment of
      GBM in Nova Scotia and may be of value as an initial attempt to analyze costs of
      treatment of GBM in Canada.

PMID- 11252297
TI  - Neural transplantation in spinal cord injury.
AB  - Although medical advancements have significantly increased the survival of spinal
      cord injury patients, restoration of function has not yet been achieved. Neural
      transplantation has been studied over the past decade in animal models as a
      repair strategy for spinal cord injury. Although spinal cord neural
      transplantation has yet to reach the point of clinical application and much work
      remains to be done, reconstructive strategies offer the greatest hope for the
      treatment of spinal cord injury in the future. This article presents the
      scientific basis of neural transplantation as a repair strategy and reviews the
      current status of neural transplantation in spinal cord injury.

PMID- 11252299
TI  - P300 in Behcet's patients without neurological manifestations.
AB  - OBJECTIVE: Behcet's disease is the association of recurrent aphthous stomatitis
      with genital ulceration and eye disease. Neurologic involvement patterns include
      meningomyelitis, a brain stem syndrome, pyramidal and extrapyramidal abnormality
      and stroke. In the present study, subclinical involvement was investigated by
      using P300 in Behcet's patients without neurological manifestation. METHODS:
      Fifteen patients and 15 healthy volunteers were accepted for the study. P300 from
      vertex (Cz) electrode sites of the 10-20 system using electrodes and motor
      response time were recorded. RESULTS: Patients had significantly prolonged
      latencies of P300 as compared to normal controls (p=0.013) but no significant
      differences in amplitude (p=1.000). Patients showed a significantly delayed motor
      response time than controls (p=0.006). Nine patients (60%) had P300 latency and
      eight patients (53.3%) had motor response time values exceeding the mean of
      controls by two standard deviations. CONCLUSION: The findings suggest that the
      P300 measures and motor response time may reflect subclinical neurologic
      involvement in Behcet's disease.

PMID- 11252300
TI  - Gait analysis in advanced Parkinson's disease--effect of levodopa and tolcapone.
AB  - OBJECTIVE: To determine the therapeutic effect of levodopa/benserazide and
      tolcapone on gait in patients with advanced Parkinson's disease. METHODS:
      Instrumental gait analysis was performed in 38 out of 40 patients with wearing
      off phenomenon during a randomized, double-blind, placebo-controlled trial of
      tolcapone. RESULTS: Gait analysis disclosed a significant improvement by
      levodopa/benserazide in walking speed, stride length and the range of motion of
      hip, knee and ankle joints. At the end of the study, both the UPDRS motor scores
      during off-period and the percentage of off time improved significantly using
      tolcapone. However, gait analysis could not confirm this improvement. With
      respect to levodopa/benserazide effect, the reduction in rigidity correlated with
      improved angular excursion of the ankle, whereas the decreased bradykinesia
      correlated with improved stride length and angular excursion of the hip and knee
      joints. CONCLUSION: The results of our gait analysis confirmed that in
      parkinsonian patients with fluctuating motor symptoms levodopa/benserazide, but
      not tolcapone, produced a substantial improvement.

PMID- 11252301
TI  - Gliomatosis cerebri.

PMID- 11252302
TI  - A 22-year-old female with visual disturbances and raised intracranial pressure.

PMID- 11252304
TI  - Wernicke's encephalopathy following gastroplasty for morbid obesity.
AB  - BACKGROUND: The syndrome of Wernicke's encephalopathy consists of two of four
      features of (1) dietary deficiency; (2) oculomotor abnormality; (3) cerebellar
      dysfunction; and (4) confusion or mild memory impairment. Predisposing risk
      factors include alcoholism, hyperemesis gravidarum and prolonged intravenous
      feeding. METHODS: A 35-year-old female developed refractory emesis, severe weight
      loss, and hypokalemia following banded gastroplasty for morbid obesity. Reversal
      of gastroplasty was performed four months following initial surgery. Following
      reversal, the patient developed confusion, ataxia, leg weakness and nystagmus.
      RESULTS: Examination of the patient demonstrated disorientation with confusion,
      vertical nystagmus worse on downgaze, diffuse weakness of the lower extremities,
      and bilateral dysmetria. Magnetic resonance imaging of the brain demonstrated
      symmetrical areas of increased T2 signal present bilaterally in the medial
      thalamic nuclei. The patient did not demonstrate any initial improvement with
      intravenous thiamine but improved over two months of follow-up. CONCLUSION:
      Wernicke's encephalopathy has been reported in the European literature as a
      complication of gastroplasty, with rare recognition of this clinical entity in
      the North American literature. This potential complication of gastroplasty may be
      preventable by nutritional intervention in subjects experiencing severe weight
      loss and emesis following surgery.

PMID- 11252303
TI  - Spinal angiolipoma.
AB  - BACKGROUND: Spinal epidural angiolipoma is a rare cause of spinal cord
      compression. We present a case and review the clinical presentation, radiological
      appearance, pathological aspects and treatment of this distinct clinico
      pathological entity. METHODS: A case of a 46-year-old woman with a five-month
      history of progressive myelopathy affecting her lower extremities is presented.
      CT and MRI revealed a large epidural fat-containing mass compressing the spinal
      cord dorsally at the T7-T8 level. A laminectomy was performed with gross total
      resection of the lesion. RESULTS: The patient's neurologic symptoms improved
      postoperatively. A two-year follow-up period has revealed no signs of tumor
      recurrence and no neurological deficit. CONCLUSION: The diagnosis of spinal
      angiolipoma should be considered in the differential diagnosis of spinal cord
      compression. Magnetic resonance imaging is the investigation of choice. The
      surgical objective is complete excision but, for anterior lesions involving bone,
      an overly aggressive approach should be tempered by an awareness of the overall
      indolent natural history of so-called "infiltrating" spinal angiolipomas that are
      only partially excised.

PMID- 11252305
TI  - TP53 mutations in a recurrent unicameral bone cyst.

PMID- 11252307
TI  - Personal reflections on the "animal-rights" phenomenon.

PMID- 11252308
TI  - Triggering of sudden death from cardiac causes by vigorous exertion.

PMID- 11252306
TI  - Polycystin-2, the protein mutated in autosomal dominant polycystic kidney disease
      (ADPKD), is a Ca2+-permeable nonselective cation channel.
AB  - Defects in polycystin-2, a ubiquitous transmembrane glycoprotein of unknown
      function, is a major cause of autosomal dominant polycystic kidney disease
      (ADPKD), whose manifestation entails the development of fluid-filled cysts in
      target organs. Here, we demonstrate that polycystin-2 is present in term human
      syncytiotrophoblast, where it behaves as a nonselective cation channel. Lipid
      bilayer reconstitution of polycystin-2-positive human syncytiotrophoblast apical
      membranes displayed a nonselective cation channel with multiple subconductance
      states, and a high perm-selectivity to Ca2+. This channel was inhibited by anti
      polycystin-2 antibody, Ca2+, La3+, Gd3+, and the diuretic amiloride. Channel
      function by polycystin-2 was confirmed by patch-clamping experiments of
      polycystin-2 heterologously infected Sf9 insect cells. Further, purified insect
      cell-derived recombinant polycystin-2 and in vitro translated human polycystin-2
      had similar ion channel activity. The polycystin-2 channel may be associated with
      fluid accumulation and/or ion transport regulation in target epithelia, including
      placenta. Dysregulation of this channel provides a mechanism for the onset and
      progression of ADPKD.

PMID- 11252309
TI  - Triggering of sudden death from cardiac causes by vigorous exertion.

PMID- 11252310
TI  - Triggering of sudden death from cardiac causes by vigorous exertion.

PMID- 11252311
TI  - Prevention of hip fracture with use of a hip protector.

PMID- 11252312
TI  - Prevention of hip fracture with use of a hip protector.

PMID- 11252313
TI  - Prevention of hip fracture with use of a hip protector.

PMID- 11252314
TI  - Prevention of hip fracture with use of a hip protector.

PMID- 11252315
TI  - Myocarditis.

PMID- 11252316
TI  - Myocarditis.

PMID- 11252317
TI  - Myocarditis.

PMID- 11252318
TI  - Case 30-2000: Churg-Strauss syndrome.

PMID- 11252319
TI  - Biventricular cardiac thrombosis during interleukin-2 infusion.

PMID- 11252320
TI  - Costs,competence, and consumerism: challenges to medicine in the new millennium.

PMID- 11252321
TI  - Occurrence and epidemiology of resistance to virginiamycin and streptogramins.

PMID- 11252322
TI  - The suppository form of antibiotic administration: pharmacokinetics and clinical
      application.
AB  - The rectal route of antibiotic administration might be used effectively when
      other routes of administration are inadequate or unsuitable. With the use of
      various adjuvants, the rectal route can provide satisfactory pharmacokinetics and
      acceptable local tolerance. Experiments in animals have demonstrated the
      influence of the pharmaceutical formulation of suppositories on the rectal
      absorption and systemic distribution of beta-lactams and aminoglycosides. In
      healthy volunteers and in children under treatment, similar adjuvants--mainly
      glyceride mixtures or non-ionic surface agents--have increased the rectal
      absorption of aminopenicillins, cephalosporins and macrolides. Other antibiotics,
      including metronidazole and cotrimoxazole, have been investigated in respect of
      their potential rectal administration.

PMID- 11252323
TI  - Detection of OXA-4 beta-lactamase in Pseudomonas aeruginosa isolates by genetic
      methods.
AB  - In Pseudomonas aeruginosa, resistance to cefclidin is usually associated with
      resistance to another third-generation cephalosporin, ceftazidime. In this study
      we analysed 22 isolates of P. aeruginosa, collected at Showa University Fujigaoka
      Hospital between 1992 and 1993, which were resistant to cefclidin but susceptible
      to ceftazidime. All polymerase chain reaction (PCR) products amplified by a
      primer pair covering the full-length gene of OXA-4 (also OXA-1) precursor beta
      lactamase were 0.84 kb in length. The isoelectric points of the beta-lactamases
      produced by these isolates were typical of the OXA-4 type of beta-lactamase (pl
      7.5) rather than the OXA-1 type (pl 7.4). All PCR products at 216 bp were
      amplified by the primer pair covering the A928-->T point mutation, which
      corresponds to the Asp48-->Val amino acid substitution of OXA-1 beta-lactamase to
      form OXA-4 beta-lactamase. These single-strand conformation polymorphism (SSCP)
      patterns are typical of the OXA-4 gene, rather than the OXA-1 gene, demonstrating
      that these enzymes can be classified by SSCP analyses based on the PCR method.
      Although OXA-4 beta-lactamase is generally plasmid-mediated, the chromosomal DNA
      of these isolates, but not their plasmids, hybridized with the OXA-4 gene
      amplified by the PCR method. Based on these results, we suspected that the
      plasmids encoding OXA-4 beta-lactamase had been spontaneously cured, or that the
      gene had been deleted from the plasmid. The distribution of P. aeruginosa
      producing OXA-4 beta-lactamase amongst hospital wards and clinical specimens
      demonstrated that the OXA-4 enzyme in this collection period was representative
      of hospital P. aeruginosa.

PMID- 11252324
TI  - Impaired imipenem uptake associated with alterations in outer membrane proteins
      and lipopolysaccharides in imipenem-resistant Shigella dysenteriae.
AB  - Three imipenem-resistant mutants were obtained from a clinical isolate (C152) of
      Shigella dysenteriae by selection with increasing concentrations of imipenem.
      Resistance to imipenem was associated with resistance to several other beta
      lactam antibiotics. The penicillin-binding protein (PBP) patterns of the
      resistant and the wild-type strains were comparable. The permeability of the
      outer membrane proteins (OMPs) of the most resistant mutant, IM16, was lower than
      that of the parent strain C152 when imipenem and arabinose were used as test
      solutes. This mutant had lower levels of both the major OMPs of M(r) 43,000 and
      38,000. There were also differences in the patterns of lipopolysaccharide (LPS)
      of the mutants and the wild-type strain. The mutant IM16 had less short-chain LPS
      than the parent C152. Increasing imipenem resistance was also associated with a
      concomitant decrease in the level of 2-keto-3-deoxyoctonate, a component of the
      core region of LPS.

PMID- 11252325
TI  - Antimicrobial properties of liposomal polymyxin B.
AB  - The pulmonary residence time of polymyxin B has been shown to be substantially
      increased when administered as a liposomal formulation. The use of this system to
      improve the treatment of cystic fibrosis lung infections requires that the
      antimicrobial activity of polymyxin B is unaffected by the encapsulation process.
      To verify that activity against the target organism, Pseudomonas aeruginosa, was
      retained, the bactericidal activity and MICs of both free and encapsulated
      polymyxin B were determined. The roles of liposomal surface characteristics in
      determining interactions with bacterial cell surfaces were also investigated.
      Encapsulation of polymyxin B was reduced when the positively charged amphiphile,
      stearylamine (SA) was present, with entrapment efficiencies being lower than with
      neutral (egg phosphatidylcholine, EPC) or negatively charged (egg
      phosphatidylcholine:dicetylphosphate, EPC:DCP) formulations (EPC, 45.41% +/-
      0.51%; EPC:DCP 9:1, 50.81% +/- 0.79%; EPC:SA 9:1, 31.92% +/- 2.08%, n x 3). The
      bactericidal activities were compared, and it was found that polymyxin B retained
      antimicrobial activity after encapsulation. At a polymyxin B concentration of 0.3
      mg/L, both positively and negatively charged liposomal polymyxin B formulations,
      and free drug, killed all cells after 1 h. In contrast, neutral liposome
      formulations did not significantly decrease the surviving cell fraction. At 0.1
      mg/L, fewer cells were killed, and all liposomal formulations produced a
      reduction in cell numbers, which was not significantly different from free drug.
      It was found that the MICs of liposomal formulations were attributable to the
      free drug concentration achieved through release of entrapped polymyxin B.
      Enhanced activity was seen only with positively charged EPC:SA liposomes and
      those containing distearoylphosphatidylcholine (DSPC) as the bulk phospholipid.
      This is likely to be the result of favourable electrostatic interactions and
      increased liposome:cell ratios respectively. In summary, liposome encapsulation
      of polymyxin B was not detrimental to antimicrobial activity, and liposome
      surface properties and release characteristics were important in determining
      interactions with bacterial cells.

PMID- 11252326
TI  - In-vitro activity of fosfomycin against vancomycin-resistant enterococci.
AB  - The effect of fosfomycin against 69 vancomycin-resistant isolates of Enterococcus
      faecium (VanA), five of E. faecium (VanB), 11 of Enterococcus faecalis (VanA),
      three of E. faecalis (VanB), 10 of Enterococcus gallinarum (VanC1) and two of
      Enterococcus casseliflavus (VanC2) and glycopeptide-sensitive E. faecium (n = 8)
      and E. faecalis (n = 10) was tested in vitro. Fosfomycin inhibited 97%, 94% and
      96% of the vancomycin-resistant strains, according to results of agar dilution,
      broth microdilution, and a disc diffusion method (DIN 58940). The disc diffusion
      test by the NCCLS method does not include fosfomycin; using breakpoints suggested
      by Andrews et al. (< or = 11 mm, resistant; > or = 18 mm, susceptible), 5% of the
      vancomycin-resistant strains tested would have been considered fosfomycin
      resistant. Minimal inhibitory concentrations of most vancomycin-resistant
      isolates were in the intermediate sensitivity range, yielding an MIC50 of 32 mg/L
      and an MIC90 of 64 mg/L. Moreover the majority of inhibitory zone sizes by the
      disc diffusion method (DIN 58940) corresponded to intermediate susceptibility.
      These results suggest that fosfomycin at a high dosage and possibly used in
      combination with other drugs could be a potentially useful drug for the treatment
      of infections caused by vancomycin-resistant enterococci.

PMID- 11252327
TI  - Antimycobacterial activity of cerulenin and its effects on lipid biosynthesis.
AB  - Cerulenin is a potent inhibitor of fatty acid synthase (FAS) in a variety of
      prokaryotic and eukaryotic cells. Using a standardized mycobacterial
      susceptibility test, we have observed that cerulenin inhibits the growth of
      several species of mycobacteria, including tuberculous species such as
      Mycobacterium tuberculosis (H37Rv and clinical isolates) and Mycobacterium bovis
      BCG (hereafter called BCG), as well as several non-tuberculous species:
      Mycobacterium smegmatis, the Mycobacterium avium-intracellulare complex (MAC),
      Mycobacterium kansasii and others. All species and strains tested, including
      multi-drug resistant isolates of M. tuberculosis, were susceptible to cerulenin
      with MICs ranging from 1.5 to 12.5 mg/L. Two-dimensional thin-layer
      chromatography revealed different inhibition patterns of lipid synthesis between
      tuberculous and non-tuberculous mycobacteria. Cerulenin treatment resulted in a
      relative increase in phospholipids and mycolic acids in MAC and M. smegmatis,
      whereas in cerulenin-treated BCG, phospholipids and mycolic acids diminished
      relative to controls. In addition, long-chain extractable lipids (intermediate in
      polarity), triglycerides and glycopeptidolipids decreased with cerulenin
      treatment in all three species of mycobacteria tested. Qualitative changes in
      several of these lipid classes indicate inhibition in the synthesis of
      intermediate and long-chain fatty acids. Our results suggest that cerulenin's
      primary effect may be inhibition of intermediate and long-chain lipid synthesis,
      with little effect on the synthesis of other lipid classes. In addition, the BCG
      specific reduction in phospholipids and mycolic acids suggests the presence of a
      unique cerulenin-sensitive FAS system in tuberculous mycobacteria. Since
      pathogenic mycobacteria produce novel long-chain fatty acids, inhibition of fatty
      acid synthesis offers a potential target for the development of antimycobacterial
      drugs.

PMID- 11252328
TI  - Amphotericin B susceptibility testing of Candida lusitaniae isolates by flow
      cytofluorometry: comparison with the Etest and the NCCLS broth macrodilution
      method.
AB  - A flow cytofluorometric susceptibility test (FCST) was used for rapid
      determination of the susceptibility of Candida lusitaniae isolates to
      amphotericin B. The test is based on the decrease in fluorescence intensity of
      cells stained with 3,3'-dipentyloxacarbocyanine iodide (DiOC5(3)), a membrane
      potential-sensitive cationic dye, after drug treatment. A total of 58 C.
      lusitaniae clinical isolates including strains known to be amphotericin B
      resistant on the basis of in-vivo and/or in-vitro data were tested. MICs were
      determined concurrently by the NCCLS broth macrodilution method and the Etest,
      both with antibiotic medium 3. Regression analysis demonstrated that the data
      from the FCST and the Etest were better correlated (r = 0.93, n = 59, P < 0.001)
      than those from the FCST and the NCCLS method (r = 0.63, n = 59, P < 0.001). The
      FCST readily identified a series of putatively susceptible and resistant
      isolates. Our study points out the advantages of the flow cytometry approach in
      antifungal susceptibility testing of yeasts, since speed remains a major problem
      in conventional tests.

PMID- 11252329
TI  - Ability of teicoplanin and vancomycin to induce contraction of, and histamine
      release from, pulmonary tissue of humans, monkeys and guinea pigs.
AB  - To assess the safety of teicoplanin and vancomycin with respect to airway tissue,
      we evaluated whether these two antibiotics induce pulmonary tissue contraction
      and histamine release in human, monkey and guinea pig specimens in vitro. The
      effects of these drugs on the release of histamine from monkey blood leucocytes
      and mouse bone marrow-derived mast cells (BMMC) were also studied. Neither
      teicoplanin nor vancomycin (10(-6)-10(-3) g/mL) induced contractions of guinea
      pig trachea or lung parenchyma. Similarly, these drugs induced no appreciable
      change in the resting tonus of cynomolgus monkey bronchus or lung parenchyma. The
      tonus of monkey trachea was not influenced by teicoplanin, whereas 10(-3) g/mL
      vancomycin caused contraction. The spontaneous tonus of human lung parenchyma was
      not altered by teicoplanin or vancomycin, and that of the bronchus was not
      influenced by teicoplanin; however, 10(-3) g/mL vancomycin elicited obvious
      contraction of the bronchus. Neither drug promoted the release of significant
      amounts of histamine from these pulmonary tissues or from monkey blood leucocytes
      and BMMC. These results suggest that, compared with vancomycin, teicoplanin may
      be associated with a lower risk of inducing bronchospasm when used for inhalation
      therapy.

PMID- 11252330
TI  - Surveillance of the overall consumption of antibacterial drugs in humans,
      domestic animals and farmed fish in Norway in 1992 and 1996.
AB  - The annual overall consumption of antibacterial drugs in Norway, categorized into
      human use, use in domestic animals and in farmed fish, was estimated from
      wholesaler and feed-mill sales statistics. Comprehensive data on drug consumption
      in human medicine in Norway are published on a regular basis on behalf of the
      drug authorities. These data, including use of antibacterial drugs, are expressed
      as the number of defined daily doses (DDD)/1000 inhabitants/year. DDD cannot be
      employed to compare antibiotic consumption in human and veterinary medicine as it
      is possible to calculate such data for only a few veterinary drugs. The only
      parameter for which data are generally available, so far, is the amount used in
      kilograms of active substance, which is the unit of measurement chosen in this
      study. It was found that annual overall sales of antibacterial drugs in Norway,
      including antibacterial and ionophore feed additives, decreased from 77 tonnes in
      1992 to 49 tonnes in 1996, a 37% reduction. The use in 1996 in human medicine,
      animals and farmed fish was 35 tonnes, 13 tonnes and 1 tonne, respectively. While
      the annual amounts used in human medicine remained unchanged from 1992 to 1996,
      therapeutic use in fish farming declined by 96%. In domestic animals, therapeutic
      use and use as feed additives declined by 17% and 5%, respectively. During the
      study period, the size of the human and domestic animal populations at risk
      remained almost constant, while the biomass (weight) of farmed fish at risk
      increased by > 100%. This implies that both the absolute and relative consumption
      of antibacterial drugs in Norway decreased substantially during the study period.
      The use of antibacterial drugs, both in humans and in domestic animals, has
      changed in favour of penicillins, this being in accordance with general
      recommendations. The reduction in the use of antibacterial drugs in farmed fish
      has been almost solely due to the introduction of oil-adjuvanted vaccines against
      furuncolosis. It is concluded that the decline in the amount of antibacterial
      drugs used in domestic animals, and the changes with regard to choice of drugs,
      could be mainly attributed to changes in prescribing behaviour following advice
      and recommendations. Moreover, the overall use of antibacterial drugs in Norway
      is very low compared with that in most other countries and has been significantly
      reduced during the 1990s.

PMID- 11252331
TI  - The prevalence of aminoglycoside resistance and corresponding resistance genes in
      clinical isolates of staphylococci from 19 European hospitals.
AB  - Aminoglycosides still play an important role in antistaphylococcal therapies,
      although emerging resistance amongst staphylococci is widespread. To further our
      understanding of the prevalence of aminoglycoside resistance in Europe, we tested
      699 and 249 consecutive unrelated clinical isolates of Staphylococcus aureus and
      coagulase-negative staphylococci (CNS), respectively, from the SENTRY
      Antimicrobial Surveillance Program, for susceptibility to gentamicin, tobramycin,
      kanamycin and streptomycin, and examined the relationship between susceptibility
      to these antimicrobials and susceptibility to methicillin. Three hundred and
      sixty-three staphylococcal isolates demonstrated resistance to at least one of
      the aminoglycosides tested; all of these isolates were screened for the presence
      of aac(6')-Ie + aph(2"), ant(4')-Ia and aph(3')-IIIa, the genes encoding the most
      clinically relevant aminoglycoside-modifying enzymes. S. aureus isolates derived
      from hospital-acquired pneumonia tended to be more resistant to aminoglycosides
      and methicillin than isolates from blood or wound infections. In S. aureus,
      resistance to aminoglycosides was closely associated with methicillin resistance.
      Susceptibility of S. aureus to gentamicin has decreased by 9% from previous
      European studies to a current level of 77%, while susceptibility of CNS,
      currently at 67%, has increased by 21%. Geographical variation occurred,
      correlating with methicillin resistance, although intra-country variation was
      considerable. aac(6')-Ie + aph(2"), ant(4')-Ia and aph(3')-IIIa were found
      throughout Europe in 68%, 48% and 14% respectively of staphylococci resistant to
      at least one aminoglycoside. aph(3')-IIIa was considerably more common in
      methicillin-susceptible S. aureus and CNS isolates; the reverse was true for the
      other two resistance genes. The prevalence of ant(4')-Ia and aph(3')-IIIa genes
      in aminoglycoside-resistant staphylococci was significantly greater than that
      reported in previous European studies.

PMID- 11252333
TI  - Risk factors for amphotericin B-induced nephrotoxicity.
AB  - The association of amphotericin B with nephrotoxicity is well known, but risk
      factors for this complication are not well characterized. One hundred and seventy
      eight patients who received > 3 days of intravenous amphotericin B and a minimal
      total cumulative dose > 100 mg were reviewed retrospectively. The mean age,
      average cumulative dose of amphotericin B and duration of therapy were 46 +/- 22
      years, 536 +/- 547 mg and 16.6 +/- 8.2 days, respectively. Eighty-six percent of
      patients received amphotericin B for empirical therapy of febrile neutropenia.
      Various definitions of nephrotoxicity were used; these were as follows (the
      incidence of nephrotoxicity as determined by the given definition is given in
      parentheses): definition 1, a change in creatinine of > 46 mumol/L over baseline
      (50%); definition 2, a doubling of creatinine over baseline (49%); definition 3,
      a change in creatinine of > 92 mumol/L (29%); definition 4, a doubling and/or a
      change in creatinine of > 92 mumol/L (49%); definition 5, an increase in
      creatinine to > 230 mumol/L (8%). Multivariate analysis showed that
      nephrotoxicity was associated with a greater cumulative dose of amphotericin B
      and receipt of concomitant nephrotoxic drugs for all definitions (P < 0.05). In
      those patients who experienced severe nephrotoxicity (creatinine increased to >
      230 mumol/L), cyclosporin therapy was the most significant risk factor (odds
      ratio 18.8, P = 0.022). Haemodialysis was necessary in one patient, but multiple
      concomitant risk factors for renal dysfunction were present. No patient
      experienced irreversible nephrotoxicity. These findings allow for stratification
      of patients at risk for amphotericin B-induced nephrotoxicity and rational use of
      alternative agents.

PMID- 11252332
TI  - The control of hyperendemic glycopeptide-resistant Enterococcus spp. on a
      haematology unit by changing antibiotic usage.
AB  - The rectal carriage of glycopeptide-resistant Enterococcus spp. (GRE) had been
      established at approximately 50% in a series of prevalence studies on a busy
      haematological malignancy unit. The aim of this study was to reduce the chance of
      patients acquiring GRE. A prospective three-phase sequential study was performed.
      In Phase 1, the acquisition rate of GRE detectable by rectal swab was measured
      without any intervention for a period of 4 months. For the following 8 months
      (Phase 2), the first-line treatment for febrile neutropenic episodes was changed
      from monotherapy with ceftazidime to piperacillin/tazobactam. In addition, an
      intense education programme was introduced to improve hygiene to reduce the risk
      of case-to-case spread. In the final 4 months (Phase 3), ceftazidime was again
      used as the first-line antimicrobial, while continuing the same level of training
      in relation to hygiene. The carriage of GRE was measured from rectal swabs done
      weekly. During the initial 4 months, at any time, 40-50% of patients in the unit
      were colonized with GRE, and 43 of 75 (57%) new patients initially negative for
      GRE acquired it within 6 weeks of their admission. In Phase 2, 25 patients out of
      129 (19%) acquired GRE, with the acquisition rate falling progressively so that
      in the last 3 months, only one new patient acquired GRE (logrank comparison of
      probabilities for cohort 1 vs cohort 2b: P < 0.0001). A return to ceftazidime in
      Phase 3 was associated with a return of the risk of acquiring detectable GRE
      colonization, despite continued hygiene teaching and surveillance, with 21 out of
      58 patients (36%) acquiring GRE (cohort 1 vs cohort 3: P = 0.08). Glycopeptide
      usage was not reduced during the period of the study. Clinical cases were seen
      only in Phases 1 and 3. Although the reduction in the risk of acquiring GRE may
      have been due in part to hygiene practices as well as to the change in
      antimicrobial usage, or may have occurred spontaneously for other reasons, the
      return of the problem with the reintroduction of ceftazidime strongly suggests
      that this antibiotic was responsible for encouraging the acquisition of
      detectable GRE.

PMID- 11252334
TI  - Prevalence and degree of expression of the carbapenemase gene (cfiA) among
      clinical isolates of Bacteroides fragilis in Nottingham, UK.
AB  - The carbapenemase gene (cfiA) was detected in 12 (6.9%) out of 175 clinical
      isolates of Bacteroides fragilis from Nottingham, three times the frequency
      reported from France. Only one gene copy was present in all cases. Eleven (6.3%)
      of the cfiA-positive isolates were susceptible to imipenem or meropenem (MIC < 8
      mg/L); strains of this type have the potential to convert to high-level
      resistance. One isolate (0.6%) displayed resistance to both carbapenem
      antibiotics and was associated with specific carbapenemase activity six times
      that of the sensitive isolates.

PMID- 11252335
TI  - Relationship between haemolysis production and resistance to fluoroquinolones
      among clinical isolates of Escherichia coli.
AB  - The activities of ampicillin, amoxycillin-clavulanic acid, gentamicin,
      tetracycline, nalidixic acid, ciprofloxacin, pefloxacin and trovafloxacin against
      207 consecutive clinical isolates of Escherichia coli were determined. Fifty-six
      (27.3%) isolates were haemolytic. The percentages of resistance to quinolones and
      tetracycline, but not to other agents, among haemolytic isolates were
      significantly lower (P < 0.05) than among non-haemolytic isolates. Ciprofloxacin
      resistant mutants obtained from ciprofloxacin-susceptible haemolytic isolates
      still produced haemolysis. It is concluded that most quinolone-resistant clinical
      isolates of E. coli are non-haemolytic, although haemolysis is produced by
      quinolone-resistant mutants derived from haemolytic quinolone-susceptible
      strains.

PMID- 11252336
TI  - Relationship between genetic alteration of the rpsL gene and streptomycin
      susceptibility of Mycobacterium tuberculosis in Japan.
AB  - We have investigated the effect of genetic alterations in the rpsL gene on the
      MICs of streptomycin for Mycobacterium tuberculosis strains. Direct DNA
      sequencing showed a point mutation in 23/121 strains; in 18 strains the mutation
      was associated with an amino acid change. The MICs of streptomycin in 22 out of
      23 point-mutated strains were > or = 256 mg/L. Restriction fragment length
      polymorphism (RFLP) analysis showed mutations at codon 43 in all 18 strains with
      point mutations in the same codon. Our results suggest that both RFLP and base
      sequencing analysis of the rpsL gene are useful for the rapid prediction of
      highly streptomycin-resistant strains of M. tuberculosis.

PMID- 11252338
TI  - In-vitro bactericidal activity of cefpirome and cefamandole in combination with
      glycopeptides against methicillin-resistant Staphylococcus aureus.
AB  - The bactericidal activity in vitro of cefpirome plus either vancomycin or
      teicoplanin was compared with that of a cefamandole-vancomycin combination
      against ten clinical isolates of homogeneous methicillin-resistant Staphylococcus
      aureus. Cefpirome (0.125 x MIC) combined with vancomycin (0.5-2 x MIC) or
      teicoplanin (0.5-4 x MIC) acted synergically against the ten isolates. Similar
      effects were observed with the cefamandole-vancomycin combination, except that
      for one isolate, higher cefamandole concentrations (0.25-1 x MIC) were required.

PMID- 11252339
TI  - In-vitro activity of five antifungal agents against uncommon clinical isolates of
      Candida spp.
AB  - A broth microdilution method and an agar dilution method were used for testing
      fluconazole, itraconazole, ketoconazole, flucytosine and amphotericin B against
      98 clinical isolates belonging to seven species of Candida. The approximate rank
      order of fluconazole MICs was Candida lusitaniae approximately Candida kefyr <
      Candida famata approximately Candida guilliermondii < Candida pelliculosa
      approximately C. lipolytica approximately Candida inconspicua. Candida lypolitica
      and C. pelliculosa were the species least susceptible to itraconazole and
      ketoconazole. Flucytosine MICs revealed the highest prevalence of resistant
      strains among C. lipolytica and C. lusitaniae. All isolates were susceptible to
      amphotericin B.

PMID- 11252337
TI  - The bactericidal activities of HMR 3004, HMR 3647 and erythromycin against gram
      positive bacilli and development of resistance.
AB  - The bactericidal activities of two new ketolides, HMR 3004 and HMR 3647, and the
      potential to develop resistance to these two antibiotics were studied in Gram
      positive bacilli. As judged by time-kill kinetics both ketolides were mostly
      bacteriostatic, being bactericidal against only highly susceptible isolates of
      Corynebacterium striatum (two isolates) and Corynebacterium minutissimum (one
      isolate). Spontaneous resistant mutants were detected in seven of 30 strains
      tested, mainly in Rhodococcus equi, C. minutissimum and C. striatum, with a very
      low frequency of mutation (10(-12)-10(-15)).

PMID- 11252341
TI  - Serum protein binding of itraconazole and fluconazole in patients with diabetes
      mellitus.
AB  - The protein binding of itraconazole and fluconazole in the serum of patients with
      insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus was
      investigated in vitro. The unbound percentage of itraconazole in patients with
      IDDM and NIDDM was significantly higher than that in healthy volunteers. In
      contrast, there were no significant differences in fluconazole protein binding. A
      negative correlation was established between itraconazole protein binding and
      albumin concentration, and a positive correlation with free fatty acid
      concentration. The existence of a larger percentage of unbound itraconazole in
      diabetes patients could imply a change in drug disposition and an alteration in
      the effect of the drug. This should be taken into consideration in long duration
      treatment, especially in view of the non-linear kinetics of itraconazole.

PMID- 11252342
TI  - Continuous infusion ceftazidime in intensive care: a randomized controlled trial.
AB  - We randomized 18 critically ill patients to receive ceftazidime 6 g/day by
      continuous infusion or bolus dosing (2 g 8 hourly), each with a loading dose of
      12 mg/kg ceftazidime. During the first 8 h, plasma ceftazidime concentration fell
      below 40 mg/L in only one patient (trough 38 mg/L) from the infusion group,
      compared with eight from the bolus group (2-33 mg/L) for periods ranging from 73
      to 369 min. Thereafter all infusion patients remained above 40 mg/L for 40 h of
      study versus 20-30% of bolus patients. The pharmacokinetic and pharmacodynamic
      characteristics of ceftazidime suggest that continuous infusions should be
      clinically investigated in outcome studies.

PMID- 11252340
TI  - Structural changes in rat Pneumocystis carinii surface antigens after terbinafine
      administration in experimental P. carinii pneumonia.
AB  - Terbinafine is a synthetic antifungal agent which has recently been found to be
      highly effective against Pneumocystis carinii. This study evaluated the efficacy
      of terbinafine on rat P. carinii antigenic profile and the immune response by
      Western blot analysis, in comparison with atovaquone and co-trimoxazole in rats
      with pneumocystosis. Terbinafine was shown to target two specific major antigens,
      particularly those of 116 and 35-40 kDa. Antibodies reactive against these
      moieties were found in all rats treated with atovaquone and co-trimoxazole, but
      not in those treated with terbinafine. These surface antigen modifications could
      be related to disease severity and could provide additional information for
      monitoring the efficacy of this treatment.

PMID- 11252343
TI  - The influence of factors affecting the 'critical population' density of inocula
      on the determination of bacterial susceptibility to antibiotics by disc diffusion
      methods.

PMID- 11252344
TI  - Sensitivity testing of Pseudomonas aeruginosa to ciprofloxacin: comparison of the
      modified Stokes' method with MIC results obtained by the Etest.

PMID- 11252345
TI  - Seasonal variation in fluoroquinolone prescribing.

PMID- 11252347
TI  - Brainstem cavernoma.

PMID- 11252346
TI  - Non-specific immunotherapy with bacille Calmette-Guerin (BCG).

PMID- 11252348
TI  - Timeline: pioneers in cerebral aneurysms.

PMID- 11252349
TI  - International Digest of Health Legislation.

PMID- 11252350
TI  - Nucleotide sequence and phylogenetic analysis of long terminal repeats of human
      endogenous retrovirus K family (HERV-K) on human chromosomes.
AB  - It has been suggested that human endogenous retroviruses K family (HERV-K) has a
      role in disease, and solitary long terminal repeats (LTRs) of HERV-K have been
      potentially capable of affecting the expression of closely located genes. Using
      the human monochromosomes 8, 9, 17, and 18, with specific PCR primers, we
      identified thirty-four sequences of new HERV-K LTRs. Those LTR elements were
      analyzed phylogenetically with the human-specific HERV-K LTRs using neighbor
      joining and maximum parsimony methods. Clones HKL8-5, HKL9-5, and HKL9-8 are
      related by more than 99% homology with the human-specific HERV-K LTRs. The HKL9-5
      clone on chromosome 9 was 100% identical with the sequences of human-specific
      LTR, AC002400, on chromosome 16. The findings suggest that there has been recent
      proliferation, transposition, or chromosomal translocation of HERV-K LTR elements
      on human chromosomes.

PMID- 11252351
TI  - Genome of human hepatitis C virus (HCV): gene organization, sequence diversity,
      and variation.
AB  - Hepatitis C virus (HCV) is the major etiologic agent of non-A, non-B hepatitis.
      HCV infection frequently causes chronic hepatitis, which progresses to liver
      cirrhosis and hepatocellular carcinoma. Since the discovery of HCV in 1989, a
      large number of genetic analyses of HCV have been reported, and the viral genome
      structure has been elucidated. An enveloped virus, HCV belongs to the family
      Flaviviridae, whose genome consists of a positive-stranded RNA molecule of about
      9.6 kilobases and encodes a large polyprotein precursor (about 3000 amino acids).
      This precursor protein is cleaved by the host and viral proteinase to generate at
      least 10 proteins: the core, envelope 1 (E1), E2, p7, nonstructural (NS) 2, NS3,
      NS4A, NS4B, NS5A, and NS5B. These HCV proteins not only function in viral
      replication but also affect a variety of cellular functions. HCV has been found
      to have remarkable genetic heterogeneity. To date, more than 30 HCV genotypes
      have been identified worldwide. Furthermore, HCV may show quasispecies
      distribution in an infected individual. These findings may have important
      implications in diagnosis, pathogenesis, treatment, and vaccine development. The
      hypervariable region 1 found within the envelope E2 protein was shown to be a
      major site for the genetic evolution of HCV after the onset of hepatitis, and
      might be involved in escape from the host immunesurveillance system.

PMID- 11252352
TI  - A novel microarray strategy for detecting genes and pathways in microbes with
      unsequenced genomes.
AB  - Expression profile analysis of genes provides valuable information concerning the
      genetic response of cells to stimuli. We describe an adaptation of this
      technology that can be used to probe for the expression of specific families of
      genes in microbial species. In our method a combination of sets of
      oligonucleotide probes representing fingerprint sequences specific to protein
      families is used to identify the presence and expression levels of family
      homologs in a microbial cell. We demonstrate computationally, using exemplars,
      that when the cDNA complement from an organism is sequentially screened against a
      set of specific motif oligonucleotides, statistically significant information can
      be obtained concerning the expression of the corresponding genes. This method can
      be used to identify specific genes and pathways simultaneously in several
      organisms of interest even in the absence of sequence information from the
      organisms.

PMID- 11252353
TI  - Identification of four genes of the Brucella melitensis ATP synthase operon F0
      sector: relationship with the Rhodospirillaceae family.
AB  - We have determined the nucleotide sequence of a cloned DNA fragment from the
      human and animal pathogen Brucella melitensis. Four genes were identified from a
      4069 bp fragment, corresponding to the B. melitensis a, c, b', and b subunits of
      the ATP synthase F0 sector operon. A duplicated and divergent copy of the b
      subunit gene was observed. This feature has been found only in photosynthetic
      bacteria and chloroplasts. In addition, the gene cluster was separated from the
      F1 sector, a characteristic described only for the Rhodospirillaceae family.

PMID- 11252354
TI  - The mammalian FEN-1 locus: structure and conserved sequence features.
AB  - Flap endonuclease 1 (FEN-1) is an enzyme that is very important for DNA
      replication in all eukaryotes because it cleaves the 5' DNA flaps that arise
      between Okazaki fragments. In addition, FEN-1 is important for base excision
      repair and for nonhomologous DNA end joining in all eukaryotes from yeast to
      human. Here we report the structure and sequence of the murine genomic FEN-1
      locus, and we compare it to the human FEN-1 locus. The transcriptional initiation
      zone of FEN-1 is within a CpG island, and the coding region of FEN-1 is a single
      exon in both the murine and human genomes. There are striking regions of
      nucleotide sequence homology within the 5' or 3'UTR or immediately upstream of
      the 5'UTR. These regions range from 30 to 230 bp. The functions of these
      conserved sequence blocks could be in transcriptional regulation, or they may
      represent a gene that overlaps in its initiation zone with FEN-1, but is oriented
      in the opposite transcriptional direction.

PMID- 11252355
TI  - Effects of PKC inhibitors on suppression of thermotolerance development in tsAF8
      cells.
AB  - Effects of protein kinase C (PKC) inhibitors (H7, staurosporine, calphostin C) on
      thermotolerance development were investigated in temperature sensitive tsAF8
      cells derived from Syrian hamster BHK21 cells. Cells were pre-heated at 45
      degrees C for 20 min, incubated at 34 degrees C with PKC inhibitors for varying
      lengths of time, i.e. 1.25-10.0 h, and then heated at 45 degrees C for 30 min.
      Increasing survival fractions after the second heat treatment was inhibited by
      the treatment with H7 (40-160 microM), with staurosporine (0.05-1.0 microM), and
      with calphostin C (0.8, 1.2 microM) in a concentration dependent manner. When the
      concentrations of these PKC inhibitors were low, the restraint of increasing
      survival fractions was temporary, since survival fractions increased 3-7.5 h
      after pre-heating. However, the survival fractions were almost constant by the
      treatment with 160 microM H7 and 1.0 microM staurosporine. Induction of HSP72
      after heat stress was investigated in tsAF8 and BHK21 cells. Cells were heated at
      45 degrees C for 20 min and incubated at 34 or 39.7 degrees C (tsAF8), at 37
      degrees C (BHK21). Intensity of intracellular fluorescence from HSP72 was
      measured by flow cytometry. HSP72 was induced in BHK21 cells, but there was no
      definite induction of HSP72 in tsAF8 cells at either 39.7 or 34 degrees C. These
      results suggest that PKC is related with the thermotolerance development in tsAF8
      cells; however, HSP72 is not involved in the thermotolerance development in tsAF8
      cells.

PMID- 11252356
TI  - Planning of hyperthermic treatment for malignant glioma using computer
      simulation.
AB  - Interstitial hyperthermia was applied using a radiofrequency generator in the
      treatment of four malignant glioma patients who had especially deep seated brain
      tumours or were at high risk. Prior to heating tumours, treatment planning based
      on an accurate prediction of temperature distribution is essential. The present
      paper introduces a novel treatment planning method and discusses its clinical
      efficacy. The two-dimensional finite element method was used for simulation of
      temperature distribution, which was calculated using the bioheat transfer
      equation. This technique was applied to plan treatment. Temperature was measured
      at two points during heating and these values were compared with those estimated
      by the simulation. In addition, the area of the contrast enhanced (CE) rim on the
      pre-heating computed tomography (CT) image was compared with the low density area
      of the CE rim on the post-heating CT image, which was obtained within 2 months
      after heating. The optimal position and number of radiofrequency (RF) electrodes
      to include the outside of the CE rim in the simulated area above 42 degrees C
      contour could be easily determined using this planning system in all cases. The
      temperature estimated by the simulation was in good agreement with the actual
      values obtained (within 0.4 degrees C). The post-heating CT image revealed that
      the hyperthermic procedure described herein achieved more than an 80% low density
      area within the CE rim in all cases (mean 86.0%). These results demonstrate that
      this novel treatment planning method may prove to be a clinically valuable tool
      in the treatment of malignant glioma with RF electrodes.

PMID- 11252357
TI  - The significance of accurate dielectric tissue data for hyperthermia treatment
      planning.
AB  - For hyperthermia treatment planning, dielectric properties of several tissue
      types are required. Since it is difficult to perform patient specific dielectric
      imaging, default values based on literature data are used. However, these show a
      large spread (approximately 50%). Consequently, it is important to know what
      limit this spread imposes on the accuracy of the SAR and subsequently on the
      temperature distributions. Hyperthermia treatment plans performed with different
      values for the dielectric properties were compared. This showed that a spread of
      50% resulted in the average absolute difference of approximately 20% in both SAR
      and temperature distributions (heat sink approach) for regional hyperthermia. For
      interstitial hyperthermia, a spread of 25% resulted in the averaged absolute
      difference of approximately 10% in the SAR distributions and 5% in the
      temperature distributions (heat sink approach). Considering other problems that
      hamper hyperthermia treatment planning, it can be concluded that default values
      for the dielectric properties suffice.

PMID- 11252358
TI  - A dynamic two-dimensional phantom for ultrasound hyperthermia controller testing.
AB  - A new thin layer phantom for testing hyperthermia controllers has been
      constructed and evaluated using an ultrasound hyperthermia system. The phantom's
      thermal behaviour agrees with the characteristics of the Pennes' bio-heat
      transfer equation (BHTE). In particular, the experimental and theoretical results
      agree in the following ways. First, with respect to the power deposition: for a
      given power magnitude and scan radius, the shape of the temperature distribution
      across the phantom corresponds to the shape predicted by the BHTE and the
      experimental and theoretical temperature values agree closely; when the power
      magnitude is varied at a fixed scan radius, the average temperature of the
      phantom varies linearly with the applied power, and as the scan radius is varied
      at a fixed power magnitude, the average temperature increases with decreasing
      scan radius size. Secondly, with respect to perfusion: increasing or decreasing
      the flow rate over the phantom simulates an increase or decrease in the BHTE
      perfusion term, and the estimated perfusion values are dependent on flow rate
      only, and are not functions of power or geometry. The combination of these
      experimental and theoretical results validate the phantom's potential for testing
      feedback control systems, particularly for future use in the development and
      verification of model-based controllers. The use of this phantom should improve
      and accelerate the testing and evaluation of feedback control systems, and reduce
      the need for animal and human testing.

PMID- 11252360
TI  - Temperature data and specific absorption rates in pelvic tumours: predictive
      factors and correlations.
AB  - The system BSD 2000 has been in clinical use for regional hyperthermia for more
      than 10 years. Several technical details of this hyperthermia system, as well as
      the results of clinical studies employing this system have been investigated. The
      intention of this paper is to investigate the correlation between technical
      efficiency or feasibility of hyperthermia with the BSD 2000, in terms of power
      densities and temperatures depending upon parameters such as tumour histology,
      tumour location, patient age, patient sex, and patient cross section. The
      possible conclusions of predictive factors derived from the above correlations
      were closely scrutinized. Data acquired from 772 treatment sessions of 190
      patients with pelvic tumours, mainly sarcomas and carcinomas of the rectum,
      cervix, prostate and anus, have been evaluated. For every session, index
      temperatures T90 (temperature attained at 90% of tumour related measurement
      points), cumulative minutes for T90 > Tref, tumour related power density (SAR:
      specific absorption rate, in W/kg) and the effective perfusion Weff (in ml/100 g
      min) were calculated. Temperatures were measured either invasively or
      endoluminally. The statistics software SPSS was employed subsequently for
      univariate, as well as multivariate analyses. The results exhibit that index
      temperatures mainly depend on the power density SAR and the hyperthermia induced
      effective perfusion. The total power P (in 100 W) and, complementarily, the
      relative power density absolute value(SAR) (= SAR/P) seem to have lesser
      influence. Clear differences between the tumour entities were established
      regarding their index temperatures and temperature distributions. SAR, Weff and P
      were correlated with several anatomical, biological and clinical factors.
      Sessions rendering low index temperatures and SAR values also revealed decreased
      individual tolerance to the treatment. This clearly displays that power-induced
      side effects define the limits of the efficiency of regional hyperthermia.
      Equivalent relationships and correlations are derived from intratumoural and
      endoluminal thermometry. Individual limitations of regional hyperthermia caused
      by anatomical, biological and clinical factors are liable to be difficult to
      overcome with the rather restricted potentials of the BSD 2000 system to control
      the SAR distribution.

PMID- 11252359
TI  - Improved reliability of repetitive RF interstitial heating in combination with
      brachytherapy: the effective use of water.
AB  - Interstitial heating and brachytherapy are often combined in the treatment of
      cancer. In such instances, a needle-type internal electrode is inserted into the
      RALS (remotely controlled afterloading system) catheter instead of a radioactive
      source. A problem with this approach, however, is that the temperature
      distribution pattern generated by the inserted electrode varies at any given
      target region in each heating treatment, which makes it difficult to accurately
      replicate the heating treatment protocol. This variation is suspected to be
      caused by non-uniformity in the small gap between the internal electrode and the
      inner surface of the surrounding catheter, causing electric currents to flow
      between the electrode and the heating material, which differs from procedure to
      procedure. To solve this problem, the gap was filled with water of high
      permittivity, and the temperature distribution was investigated using phantoms.
      With this method, a stable and reproducible temperature rise distribution was
      obtained in the phantom experiment.

PMID- 11252361
TI  - A randomized clinical trial of radiation therapy versus thermoradiotherapy in
      stage IIIB cervical carcinoma.
AB  - To clarify the role of thermoradiotherapy for FIGO Stage IIIB cervical
      carcinomas, both the clinical response and survival of patients treated with
      radio- or thermoradiotherapy were investigated. Forty patients with Stage IIIB
      uterine cervix carcinoma were treated with external beam irradiation to the
      pelvis, combined with iridium 192 high-dose-rate intracavitary brachytherapy. All
      patients were divided randomly into the following two groups: the radiotherapy
      (RT) group of 20 patients, who underwent radiotherapy alone; and the
      thermoradiotherapy (TRT) group of 20 patients, who underwent three sessions of
      hyperthermia in addition to radiotherapy. The primary endpoint of this study was
      local complete response and survival. A complete response was achieved in 50% (10
      of 20) in the RT group versus 80% (16 of 20) in the TRT group (p = 0.048). The 3
      year overall survival and disease-free survival of the patients who were treated
      with TRT (58.2 and 63.6%) were better than those of the patients treated with RT
      (48.1 and 45%), but these differences were not significant. The 3-year local
      relapse-free survival of the patients who were treated with TRT (79.7%) was
      significantly better than that of the patients treated with RT (48.5%) (p =
      0.048). TRT, as delivered in this trial, was well tolerated and did not
      significantly add to either the relevant clinical acute or long-term toxicity
      over radiation alone. TRT resulted in a better treatment response and 3-year
      local relapse-free survival rate than RT for patients with FIGO Stage IIIB
      cervical carcinoma.

PMID- 11252362
TI  - Mad cows, and now this. Foot-and-mouth virus strikes British livestock.

PMID- 11252363
TI  - The adoption maze.

PMID- 11252364
TI  - High-tech scans offer early alerts--and needless worries.

PMID- 11252365
TI  - You owe your family so much--even your illnesses.

PMID- 11252366
TI  - Pollen forecasters see serious sneezing ahead.

PMID- 11252367
TI  - Steakhouse craze defies healthful eating edict.

PMID- 11252369
TI  - Health and endogenous growth.
AB  - The focus of endogenous growth theory on human capital formation and the physical
      embodiment of knowledge in people, suggests the integration of the growth
      supporting character of health production and the growth generating services of
      human capital accumulation in an endogenous growth framework. We show that a slow
      down in growth may be explained by a preference for health that is positively
      influenced by a growing income per head, or by an ageing population. Growth may
      virtually disappear for countries with high rates of decay of health, low
      productivity of the health-sector, or high rates of discount.

PMID- 11252368
TI  - Risk sharing as a supplement to imperfect capitation: a tradeoff between
      selection and efficiency.
AB  - This paper describes forms of risk sharing between insurers and the regulator in
      a competitive individual health insurance market with imperfectly risk-adjusted
      capitation payments. Risk sharing implies a reduction of an insurer's incentives
      for selection as well as for efficiency. In a theoretical analysis, we show how
      the optimal extent of risk sharing may depend on the weights the regulator
      assigns to these effects. Some countries employ outlier or proportional risk
      sharing as a supplement to demographic capitation payments. Our empirical results
      strongly suggest that other forms of risk sharing yield better tradeoffs between
      selection and efficiency.

PMID- 11252370
TI  - Health insurance and female labor supply in Taiwan.
AB  - We examine whether the availability of subsidized health insurance to the non
      working population in Taiwan affected the labor force participation of married
      women. Our empirical identification exploits the fact that such insurance was
      first made available to wives of government employees, before being made
      universally available in Taiwan in 1995. We find that the availability of
      insurance for non-workers was associated with a 4 percentage point decline in
      labor force participation among married women, with larger declines among women
      from low income households. Countries considering universal health insurance as
      in Taiwan should anticipate similar declines in labor force participation.

PMID- 11252371
TI  - Market restructuring and pricing in the hospital industry.
AB  - This paper examines the diagnosis related group-level (DRG) price effects of
      recent hospital mergers and acquisitions that occurred in Ohio and California.
      Empirical results indicate that hospital mergers and acquisitions increase prices
      at the DRG level. Further, price increases are greater in DRGs where the merging
      hospitals gained substantial market share compared to DRGs where the merging
      hospitals did not gain significant market share. These results suggest that DRG
      specific market share plays an important role in a hospital's post-merger pricing
      strategy.

PMID- 11252372
TI  - Avoiding health insurance crowd-out: evidence from the Medicare as secondary
      payer legislation.
AB  - The cost of expanding health insurance coverage increases when people who would
      otherwise purchase insurance obtain public coverage. This paper investigates the
      effects of one of the first efforts to target insurance benefits to the most
      needy, the 1982 medicare as secondary payer (MSP) provisions. We find strong
      evidence of low compliance with the MSP both in terms of medical bill payments
      (payment compliance) and employer-sponsored insurance coverage (coverage
      compliance). We estimate payer compliance at approximately 33%. Coverage
      compliance is lower, at under 25%. We find weak evidence that the MSP caused
      older workers to shift toward MSP-exempt jobs.

PMID- 11252373
TI  - Does cigarette price influence adolescent experimentation?
AB  - The economics literature generally agrees that state and federal excise taxes can
      play an important role in deterring adolescent smoking. Teens' apparent
      responsiveness to cigarette prices is puzzling, since the majority of adolescent
      smokers do not buy their cigarettes. Teens typically do not begin to purchase
      cigarettes until they have developed an established pattern of smoking. Previous
      studies have not had adequate measures of smoking experience to explore whether
      adolescents' price responsiveness may vary by smoking experience. This paper uses
      data from a 1993 national survey of youth smoking to explore this hypothesis.

PMID- 11252374
TI  - Omitted variable bias and hospital costs.
AB  - This research examines the impact of omitted variables on the accuracy of
      parametric hospital cost function estimations based on Quebec hospital level
      data. We assess the effect of omitted variables resulting from incomplete data on
      technology and performance measurement and on tests of the cost minimizing
      behavior of the institution. Our results show that important characteristics of
      hospital technology, such as returns to scale, are extremely sensitive to omitted
      variable bias. Similarly, estimates of hospital performance are poor indicators
      of actual performance when data are incomplete.

PMID- 11252375
TI  - Does the economics of moral hazard need to be revisited? A comment on the paper
      by John Nyman.

PMID- 11252376
TI  - Health insurance: tradeoffs revisited.
AB  - In two recent papers, [Journal of Health Economics 18(2), 141-152, Journal of
      Health Economics 18(6), 811-824] Nyman raised some questions about the welfare
      calculations and conclusions in our earlier paper [Manning and Marquis, Health
      insurance: the tradeoff between risk pooling and moral hazard, Vol. 15, 1996].
      This note discusses the erroneous criticisms in his papers. First, although, we
      estimated a Marshallian demand curve, our calculations are based on compensating
      variations that incorporate the gains from risk pooling. Second, our estimates of
      second best insurance plans indicate that some cost sharing is optimal, in
      contradiction to his assertion that our results raise questions about the
      desirability of insurance coverage. The comment also deals with other issues
      raised by Nyman.

PMID- 11252377
TI  - The income transfer effect, the access value of insurance and the Rand health
      insurance experiment.

PMID- 11252378
TI  - Antibody-based resistance to plant pathogens.
AB  - Plant diseases are a major threat to the world food supply, as up to 15% of
      production is lost to pathogens. In the past, disease control and the generation
      of resistant plant lines protected against viral, bacterial or fungal pathogens,
      was achieved using conventional breeding based on crossings, mutant screenings
      and backcrossing. Many approaches in this field have failed or the resistance
      obtained has been rapidly broken by the pathogens. Recent advances in molecular
      biotechnology have made it possible to obtain and to modify genes that are useful
      for generating disease resistant crops. Several strategies, including expression
      of pathogen-derived sequences or anti-pathogenic agents, have been developed to
      engineer improved pathogen resistance in transgenic plants. Antibody-based
      resistance is a novel strategy for generating transgenic plants resistant to
      pathogens. Decades ago it was shown that polyclonal and monoclonal antibodies can
      neutralize viruses, bacteria and selected fungi. This approach has been improved
      recently by the development of recombinant antibodies (rAbs). Crop resistance can
      be engineered by the expression of pathogen-specific antibodies, antibody
      fragments or antibody fusion proteins. The advantages of this approach are that
      rAbs can be engineered against almost any target molecule, and it has been
      demonstrated that expression of functional pathogen-specific rAbs in plants
      confers effective pathogen protection. The efficacy of antibody-based resistance
      was first shown for plant viruses and its application to other plant pathogens is
      becoming more established. However, successful use of antibodies to generate
      plant pathogen resistance relies on appropriate target selection, careful
      antibody design, efficient antibody expression, stability and targeting to
      appropriate cellular compartments.

PMID- 11252379
TI  - Accumulation of barley stripe mosaic virus is significantly reduced in transgenic
      wheat plants expressing a bacterial ribonuclease.
AB  - An rnc70 gene encoding a mutant bacterial ribonuclease III (RNase III) was
      introduced into wheat (Triticum aestivum cv. Bobwhite) by microprojectile
      bombardment. T1, T2, and T3 plants regenerated from three transgenic callus lines
      were challenged with barley stripe mosaic virus. Plants expressing RNase III
      exhibited a high level of resistance to the virus infection. This resistance was
      evidenced by the absence of virus symptoms and reduced accumulation of virions in
      these plants. The result demonstrates that this pathogen-targeted resistance
      strategy can be effectively employed in conferring resistance to viral diseases
      of cereal crops.

PMID- 11252380
TI  - Transgenic zebrafish for studying nervous system development and regeneration.
AB  - Alpha1 tubulin gene expression is induced in the developing and regenerating CNS
      of vertebrates. Therefore, alpha1 tubulin gene expression may serve as a good
      probe for mechanisms underlying CNS development and regeneration. One approach to
      identify these mechanisms is to work backwards from the genome. This requires
      identification of alpha1 tubulin DNA sequences that mediate its developmental and
      regeneration-dependent expression pattern. Therefore, we generated transgenic
      zebrafish harboring a fragment of the alpha1 tubulin gene driving green
      fluorescent protein expression (GFP). In these fish, and similar to the
      endogenous gene, transgene expression was dramatically induced in the developing
      and regenerating nervous system. Although transgene expression generally declined
      during maturation of the nervous system, robust GFP expression was maintained in
      progenitor cells in the retinal periphery, lining brain ventricles and
      surrounding the central canal of the spinal cord. When these cells were cultured
      in vitro they divided and gave rise to new neurons. We also show that optic nerve
      crush in adult fish re-induced transgene expression in retinal ganglion cells.
      These studies identified a relatively small region of the alpha1 tubulin promoter
      that mediates its regulated expression pattern in developing and adult fish. This
      promoter will be extremely useful to investigators interested in targeting gene
      expression to the developing or regenerating nervous system. As adult transgenic
      fish maintain transgene expression in neural progenitors, these fish also provide
      a valuable resource of labeled adult neural progenitor cells that can be studied
      in vivo or in vitro. Finally, these fish should provide a unique in vivo system
      for investigating mechanisms mediating CNS development and regeneration.

PMID- 11252381
TI  - Transgenic GNA expressing potato plants augment the beneficial biocontrol of
      Lacanobia oleracea (Lepidoptera; Noctuidae) by the parasitoid Eulophus
      pennicornis (Hymenoptera; Eulophidae).
AB  - The effect of expressing the gene encoding snowdrop lectin (Galanthus nivalis
      agglutinin, GNA) in transgenic potato plants, on parasitism of the phytophagous
      insect pest Lacanobia oleracea by the gregarious ectoparasitoid Eulophus
      pennicornis, was investigated in glasshouse trials. Expression of GNA (approx.
      1.0% total soluble protein) by transgenic plants significantly reduced the level
      of pest damage, thus confirming previous studies. Furthermore, the presence of
      the parasitoid significantly reduced the levels of damage incurred either by the
      transgenic or control plants when compared to those plants grown in the absence
      of the parasitoid. For the GNA expressing plants the presence of the parasitoid
      resulted in further reductions (ca. 21%) in the level of damage caused by the
      pest species. The ability of the wasp to parasitise and subsequently develop on
      the pest larvae was not altered by the presence of GNA in the diet of the host.
      E. pennicornis progeny that developed on L. oleracea reared on GNA expressing
      plants showed no significant alteration in fecundity when compared with wasps
      that had developed on hosts fed on control potato plants, although mean size and
      longevity of female parasitoids was significantly reduced. The number of F2
      progeny produced by parasitoids derived from hosts fed on GNA expressing plants
      was not significantly different to those produced by parasitoids from hosts fed
      control plants. Results from the present study demonstrate that the use of
      transgenic plants expressing insecticidal proteins can be compatible with the
      deployment of beneficial insects and that the two factors may interact in a
      positive manner.

PMID- 11252382
TI  - Recombinant human protein C expression in the milk of transgenic pigs and the
      effect on endogenous milk immunoglobulin and transferrin levels.
AB  - Colostrum and milk are natural vehicles for acquiring passive immunity and are
      valuable tools for decreasing neonatant mortality from diarrheal disease. The
      effects of recombinant human protein C (rhPC) expression levels on endogenous
      immunoglobulin and transferrin content of the milk of different lineages of
      transgenic pigs were studied. The levels of rhPC in the milk ranged from 40 to
      1200 microg/ml. Transgenic pigs with rhPC expression levels less than 500
      microg/ml had no significant differences in milk protein composition with respect
      to nontransgenic pigs. A line of transgenic pigs having rhPC expression levels of
      960-1200 microg/ml had two- to three-fold higher IgG, IgM, and secretory IgA
      concentrations compared to other transgenic and nontransgenic pig groups (P <
      0.05), and four- to five-fold higher transferrin levels than nontransgenic pigs
      (P < 0.05). Changes in milk protein composition were not associated with mastitis
      or other pathologic disruption of epithelial cell junctions as indicated by
      normal casein and albumin levels in milk. Since IgG, IgM, secretory IgA, and
      transferrin are transported into the milk by transcytosis, higher levels of these
      proteins indicate that transcyctosis in the mammary epithelial cell was likely
      upregulated in pigs having high rhPC expression levels. This study is the first
      that shows a statistically significant example that mammary tissue specific
      expression of a heterologous protein can enhance endogenous phenotypic
      characteristics of milk.

PMID- 11252383
TI  - The frequency of silencing in Arabidopsis thaliana varies highly between progeny
      of siblings and can be influenced by environmental factors.
AB  - In a collection of 111 transgenic Arabidopsis thaliana lines, silencing of the
      nptII gene was observed in 62 (56%) of the lines and three distinct nptII
      silencing phenotypes were identified. Two T-DNA constructs were used, which
      differed in distance and orientation of the marker gene relative to the border
      sequences. Comparison of the sets of lines generated with each vector, indicate
      that the T-DNA construct configuration influence the incidence of lines
      displaying silencing, as well as the distribution of silencing phenotypes. Twenty
      lines were investigated more thoroughly. The frequency of silencing varied
      between siblings in 19 lines, including three lines containing a single T-DNA
      copy. The last line showed 100% silencing. The gus gene present in both
      constructs could be expressed in the presence of a silenced nptII gene.
      Investigation of methylation at a single site in the pnos promoter revealed
      partial methylation in multi-copy lines, but no methylation in single-copy lines.
      For 16 lines, the overall frequencies of silencing differed significantly between
      control plants and plants exposed to temperature stress; in 11 of these lines at
      the 0.1% level. In several cases, the frequency of silencing in progeny of stress
      treated plants was higher than for the control group, while other lines showed
      higher frequencies of kanamycin-resistant progeny for the stress-treated sibling
      plants.

PMID- 11252385
TI  - JCAHO update. Care of patients (TX).

PMID- 11252386
TI  - Retaining good employees in tough times. Part III: Five more strategies for
      retention.

PMID- 11252387
TI  - Counseling children versus adults: what is the difference?

PMID- 11252388
TI  - 48th Annual Meeting of the Society for Gynecologic Investigation. Toronto,
      Ontario, Canada. March 14-17, 2001. Abstracts.

PMID- 11252384
TI  - Construction of gene-targeting vectors: a rapid Mu in vitro DNA transposition
      based strategy generating null, potentially hypomorphic, and conditional alleles.
AB  - Gene targeting into mammalian genomes by means of homologous recombination is a
      powerful technique for analyzing gene function through generation of transgenic
      animals. Hundreds of mouse strains carrying targeted alleles have already been
      created and recent modifications of the technology, in particular generation of
      conditional alleles, have extended the usefulness of the methodology for a
      variety of special purposes. Even though the standard protocols, including the
      construction of gene-targeting vector plasmids, are relatively straightforward,
      they typically involve time-consuming and laborious gene mapping and/or
      sequencing steps. To produce various types of gene-targeting constructions
      rapidly and with minimum effort, we developed a strategy, that utilizes a highly
      efficient in vitro transposition reaction of phage Mu, and tested it in a
      targeting of the mouse Kcc2 gene locus. A vast number and different types of
      targeting constructions can be generated simultaneously with little or no prior
      sequence knowledge of the gene locus of interest. This quick and efficient
      general strategy will facilitate easy generation of null, potentially
      hypomorphic, and conditional alleles. Especially useful it will be in the cases
      when effects of several exons within a given gene are to be studied, a task that
      necessarily will involve generation of multiple constructions. The strategy
      extends the use of diverse recombination reactions for advanced genome
      engineering and complements existing recombination-based approaches for
      generation of gene-targeting constructions.

PMID- 11252389
TI  - Driving a more effective health care market by putting consumers behind the
      wheel.
AB  - In any other rational market, the consumer drives demand, and the provider
      responds with products and services aimed at meeting individual needs. This
      rational market does not exist in today's group health care system. The
      ramifications are significant: declining consumer and provider satisfaction, out
      of-control costs, a rising uninsured population, and growing employer burdens.
      Turning this chaotic world around requires a more active and informed consumer.
      Transformation is under way with solutions like Sageo, a new e-business from
      Hewitt Associates that is revolutionizing the way health care benefits are
      offered, selected, and administered. For companies that offer Sageo's services,
      their employees and retirees gain direct access to health care coverage and
      content, enabling them to research, select, and enroll in the appropriate package
      based on their individual needs.

PMID- 11252390
TI  - When it comes to measuring value, few HMOs can make the grade.
AB  - Like all organizations, managed care organizations (MCOs) must deliver value to
      customers, and to be sure of keeping them, ensure those customers know they have
      gained value. MCOs can choose any mix of insurance, protection, or experience
      value from particular encounters with customers, or durable value from their
      relationship with customers. Many have done a good job of tracking and enabling
      employers to appreciate the impact they have had on business performance, but few
      have done the same for the health and quality-of-life they deliver to consumers.
      MCOs already participate in the delivery of significant and enduring life value
      to consumers. It makes sense to track and remind consumers of the positive
      differences MCOs make, and thereby obtain member satisfaction, retention, and
      loyalty benefits, as well as image improvements for managed care as a whole. Some
      simple and inexpensive options for both tracking and reminding consumers are
      offered for consideration, including personalized annual health reports.

PMID- 11252392
TI  - Defined contribution defined: health insurance for the next century.
AB  - The consumerism movement will dramatically affect the current payer model and
      present a new series of challenges for managed care organizations. Employers will
      fuel the changes, as they create health benefit programs that are modeled after
      retirement programs. In these cases, employers will shift a major portion of
      financial responsibility to employees, who will be asked to make buying decisions
      often previously determined by managed care organizations. New business entities
      known as health navigators will be formed to aid consumers. However, many
      structural and policy obstacles may slow or transform the consumerism movement.

PMID- 11252394
TI  - Cost-effective potential for home health care.
AB  - This article discusses the cost-effective potential of home health care. A
      forward-looking managed care system might find home health care an increasingly
      cost-effective bargain. Why is home health care evolving into a better locus for
      patient care? The home health care facilities are reducing costs and prices in
      response to new pressures from consumers and new methods of prospective payment.

PMID- 11252393
TI  - Self-directed health plans: Web-enabled alternatives to traditional managed care.
AB  - New approaches for organizing, purchasing, and financing health care services are
      rapidly emerging as viable alternatives to orthodox managed care. One of the more
      intriguing approaches, Self-Directed Health Plans (SDHPs), empowers consumers as
      the agents of change and decision making in the continuing quest for health
      system reform. Combined with a host of newly evolved Internet support utilities,
      SDHPs represent a highly advanced paradigm for health insurance. Most
      importantly, SDHPs promise to genuinely harness the power and dynamism of free
      market solutions in ways that are financially and socially sustainable, and to
      pick up the innovation process where health maintenance organizations left off.
      Thus, with SDHPs surfaces new hope that the problems facing America's health care
      system are not intractable to private sector creativity.

PMID- 11252395
TI  - Understanding costs of home and community based services.
AB  - With detailed cost information, home and community-based services (HCBS)
      providers can make intelligent choices that reduce costs without compromising
      quality and outcomes. Using cost and utilization data from a large HCBS program,
      monthly costs are estimated and related to demographic and clinical variables.
      HCBS costs are positively related to disability and cognitive impairment, but not
      to available social support. Costs vary significantly across the nursing home
      eligible population, indicating that caution is warranted when seeking to
      capitate HCBS services. Per capita costs are strongly related to program volume
      and experience, falling from $508 to $423 (16.7 percent) over the course of the
      program.

PMID- 11252396
TI  - Interview with Margaret O'Kane, President of the National Committee for Quality
      Assurance.

PMID- 11252397
TI  - Defining the parameters of case management in a managed care setting.
AB  - The authors explore how case management evolved from utilization review in order
      to address the lack of flexibility of basic utilization review. They examine case
      management's widely diverse state regulatory oversight as well as its lack of a
      clear definition. The authors then suggest three mechanisms that might be used to
      devise a universal definition of case management. For the purposes of this
      article, the authors use the term case management in connection with health
      benefits plans.

PMID- 11252398
TI  - Ambulatory care in the new millennium: the role of consumer information.
AB  - The past decade has been marked by extensive change in the organization of health
      care delivery systems (the "supply side" of health care). There has been
      relatively less change in the nature of the health care consumer (the "demand
      side" of health care). The emergence of the Internet as a consumer health care
      technology, however, should significantly affect the nature of demand. The
      Internet will prepare health care consumers to better express and evaluate care
      against their preferences. This will create additional pressure on--but
      significant positive opportunity for--ambulatory care and ambulatory care
      providers.

PMID- 11252399
TI  - Trust on the health Internet.
AB  - Trust and ethics have become common themes when discussing health on the
      Internet. By all accounts, trust is the key issue in the consumer's mind when
      considering whether or not to use a medical Web site. The user has two basic
      questions: Can I trust this information to be unbiased? Can I trust this site to
      protect my privacy? Without that trust, people are highly reluctant to become
      serious users of a health Web site, presenting a problem for managed care
      organizations whose public image already suffers from a lack of public trust.
      Health plans can re-earn that trust by providing evidence-based Information
      Therapy programs that prescribe to their members the information they need to
      make decisions and avoid medical mistakes.

PMID- 11252400
TI  - Gastric apoptosis and Helicobacter pylori infection: an intricate matter.

PMID- 11252401
TI  - Quality of life and surgical outcome after laparoscopic antireflux surgery in the
      elderly gastroesophageal reflux disease patient.
AB  - BACKGROUND: Generally, treatment of gastroesophageal reflux disease (GERD) in the
      elderly follows the same principles as for any adult patient. Currently
      laparoscopic antireflux surgery (LARS) has not been clearly established in the
      elderly patient. The aim of this prospective study was to evaluate the surgical
      outcome including quality of life after LARS in patients older than 65 years.
      METHODS: Since 1993 more than 500 patients underwent LARS in our institute. A
      total of 72 patients, older than 65 years, has been treated with laparoscopic
      'floppy' Nissen (n = 51) or Toupet (n = 21) fundoplication. The patients included
      23 women and 49 men, with a mean age of 71 years (range, 66-79 years). Quality of
      life was evaluated using the Gastrointestinal Quality of Life Index (GIQLI). The
      GIQLI was evaluated prior to surgery, and 3 months and 1 year after surgery, with
      24-h pH monitoring and esophageal manometry being performed. RESULTS:
      Intraoperative complications occurred in two patients (both injury of the
      spleen), successfully managed laparoscopically. Conversion to laparotomy and
      mortality were 0%. Postoperative complications occurred twice: one patient had a
      perianal thrombosis; one had an epileptic seizure. Three months and 1 year after
      surgery 24-h pH monitoring (mean DeMeester score: preoperative, 61.4+/-23.7; 3
      months, 8.4+/-6.4; 1 year, 7.8+/-7.2) and esophageal manometry (mean:
      preoperative, 2.3 = 1.8 mmHg; 3 months, 13.9+/-3.7 mmHg; 1 year, 12.3+/-3.2 mmHg)
      showed normal values in all patients. GIQLI increased significantly (mean:
      preoperative, 86+/-9.7 points; 3 months, 120.1+/-8.9 points; 1 year, 119.3+/-10.1
      points) after surgery and is comparable to healthy individuals (118.7 points).
      One patient suffered from severe dysphagia and required dilatation. In two
      patients laparoscopic refundoplication was necessary 1 year after the initial
      procedure because of a 'slipping Nissen' and a 'telescope phenomenon'. Three
      years after LARS (n = 32) data are comparable to I year after surgery.
      CONCLUSION: As our data show, LARS can be a safe and effective procedure that
      significantly improves quality of life in the elderly patient suffering from
      GERD. Age should no longer be a contraindication to LARS.

PMID- 11252402
TI  - Gastric secretion in cystic fibrosis in relation to the migrating motor complex.
AB  - BACKGROUND: Patients with cystic fibrosis (CF) have been claimed to have defect
      intestinal motility and gastric acid secretion. The aim of this work was to study
      the interdigestive motility and the motility-related secretions in the upper
      gastrointestinal tract in patients with CF compared to healthy controls. METHODS:
      Concomitant gastroduodenal manometry combined with intragastric perfusion was
      performed in 12 healthy volunteers and 10 patients with CF. RESULTS: Eight CF
      patients showed a normal migrating motor complex. Motility-related gastric
      secretion of acid and bicarbonate was evaluated in six patients and did not
      differ from healthy subjects. Gastric net fluid secretion was significantly
      decreased in the CF patients and bilirubin reflux was significantly increased.
      The CF patients with pancreatic insufficiency lacked motility-related variations
      in plasma levels of motilin and pancreatic peptide. CONCLUSIONS: No defect in
      fasting motility or gastric secretion of acid or bicarbonate could be seen in
      well-nourished adult CF patients. The main finding was a significantly lower net
      fluid secretion and higher bilirubin reflux compared to healthy subjects.
      Indications of a genetic relationship could be seen.

PMID- 11252403
TI  - Helicobacter pylori genotypes are associated with clinical outcome in Portuguese
      patients and show a high prevalence of infections with multiple strains.
AB  - BACKGROUND: Clinical outcome of Helicobacter pylori infection is associated with
      virulence-associated bacterial genotypes. This study assessed the relationships
      between vacA, cagA and iceA genotypes and gastric diseases in Portuguese
      patients. METHODS: A total of 319 patients were endoscoped and gastric biopsy
      specimens were studied by PCR and reverse hybridization (LiPA). RESULTS: vacA
      genotypes s1/m1, s1/m2 and s2/m2 were observed in 53%, 14.5% and 32.5% of the
      cases, respectively. The majority (93.4%) of the s1 cases were s1b and 6.6% were
      s1a. Multiple vacA genotypes were found in 37.3% of the cases. Gastric ulcer and
      gastric carcinoma were associated with the presence of vacA s1 (P = 0.008 and P <
      0.001, respectively) and vacA m1 genotypes (P = 0.007 and P < 0.001,
      respectively). Duodenal ulcers were associated with vacA s1 (P < 0.001) but not
      with the vacA m genotype (P = 0.221). cagA was present in 71.2% of the cases and
      was associated with duodenal ulcer (P < 0.001), gastric ulcer (P = 0.009) and
      gastric carcinoma (P < 0.001). iceA1 was found in 27.3% and iceA2 in 32.3% of the
      cases. In 36.7% of the isolates both iceA alleles were found, and 3.8% were
      negative for iceA. The iceA genotype was not associated with clinical outcome.
      CONCLUSIONS: vacA s1 and cagA+ H. pylori strains are associated with duodenal
      ulcer, gastric ulcer or gastric carcinoma. vacA m1 is associated with gastric
      ulcer or carcinoma but not with duodenal ulcer. Infection with multiple H. pylori
      strains is remarkably high in Portugal and is more frequent in duodenal ulcer
      patients.

PMID- 11252404
TI  - Apoptosis in different compartments of antrum and corpus mucosa in chronic
      Helicobacter pylori gastritis. An 18-year follow-up study.
AB  - BACKGROUND: The association of apoptosis was analysed in three different
      compartments (foveolar cells--FC, proliferating zone--PZ and glandular part--GP)
      of antrum and corpus mucosa specimens with development of atrophy and the extent
      of apoptosis as depending on grade of chronic inflammation, activity of gastritis
      and Helicobacter pylori colonization at two time points of an 18-year follow-up
      in an adult population from Saaremaa, Estonia, with a high prevalence of H.
      pylori infection were compared. METHODS: A total of 68 persons (31 men, 37 women;
      median age, 39 years in 1979) from a primary sample of 304 subjects, endoscoped
      in 1979 and reinvestigated by endoscopy and biopsy in 1997, were included in the
      study. The state of the gastric mucosa and the presence of H. pylori in the
      antrum and corpus mucosa were assessed in accordance with the Sydney system. The
      dynamics of apoptotic index (AI) between two time points in 1979 and 1997 was
      evaluated in antrum biopsies of 49 persons and in corpus biopsies of 64 persons.
      Apoptosis was measured using terminal deoxyuridine nucleotide nick end labelling
      (TUNEL) histochemistry. RESULTS: The antrum as well as the corpus of 2/68 persons
      were H. pylori negative at both time points. Atrophy developed in 9/68 persons in
      the antrum and in 23/68 in the corpus. In PZ and GP of the corpus mucosa as well
      as in GP of the antrum mucosa, AI decreased significantly during 18 years
      compared with initial values (P < 0.05), which was not associated with
      development of atrophy. In all compartments of the antrum and corpus mucosa,
      studied at the initial and end points of observation, AI did not reveal a
      difference in persons with and without development of atrophy (P > 0.05). In the
      samples of 1979 the highest independent effect on the value of AI in the FC
      compartment for the antrum was exerted by grade of activity of gastritis (P =
      0.01) and in GP by degree of chronic inflammation (P = 0.03), while in the
      samples of 1997 the highest effect was exerted by grade of H. pylori colonization
      (P = 0.02 and 0.03 in FC and GP, respectively). For the corpus mucosa AI was most
      strongly affected also by grade of activity of gastritis in FC compartment (P =
      0.02) and by degree of chronic inflammation in PZ (P = 0.04), but not by grade of
      H. pylori colonization. CONCLUSION: AI was not associated with development of
      atrophy, but was largely dependent on grade of activity of gastritis and degree
      of chronic inflammation; in the antrum mucosa AI depended also on grade of H.
      pylori colonization.

PMID- 11252405
TI  - Histochemical tracing of bismuth in Helicobacter pylori after in vitro exposure
      to bismuth citrate.
AB  - BACKGROUND: Bismuth-containing drugs are widely used in the treatment of
      Helicobacter pylori associated peptic ulcer. The mechanism of action of bismuth
      salts is, however, not fully understood, and at present no histochemical
      techniques for the demonstration of bismuth in H. pylori are available. The aims
      were to present a histochemical method for the detection of bismuth in H. pylori
      and to demonstrate bismuth uptake in H. pylori after in vitro exposure to bismuth
      citrate. METHODS: H. pylori cultures (the strain used in this study was CCUG
      17874), were exposed to bismuth citrate at different concentrations (0, 4.6, 80,
      200 microM) and for different lengths of time (0 min, 15 min, 1 h, 24 h, 48 h).
      The samples were fixed in glutaraldehyde, centrifuged, and exposed to
      autometallographic (AMG) development in order to detect bismuth histochemically.
      RESULTS: A detailed protocol on the AMG bismuth technique on H. pylori exposed to
      bismuth in vitro is given. This method results in easily detectable AMG grains of
      silver enhanced bismuth particles at the electron microscopical level, and shows
      that bismuth accumulates in H. pylori, predominantly near the wall of the
      bacteria. Bismuth uptake is followed by bacterial degeneration. CONCLUSION: The
      present technique with its ability to trace bismuth constitutes a valuable tool
      in the efforts of clarifying the mechanism of action of bismuth on H. pylori, and
      supports the notion that bismuth has an antimicrobial activity in itself.

PMID- 11252406
TI  - Association between the IgG subclass response, inflammation and disease status in
      Helicobacter pylori infection.
AB  - BACKGROUND: In many viral, bacterial and parasitic infections the Immunoglobulin
      G (IgG) subclass response has been shown to correlate with severity of
      inflammation and disease outcome. The aim of the present study was to investigate
      the association between the IgG subclass response to Helicobacter pylori
      infection and disease and inflammation. METHODS: Eighty-three symptomatic
      patients undergoing endoscopic examination were included in the study. Upon
      endoscopic examination, the presence of ulceration was noted and biopsy specimens
      were collected from the gastric antrum, body and transitional zone. Blood was
      also collected from each patient. Gastric biopsy sections were graded using the
      Sydney system. H. pylori specific IgG, IgG1, IgG2, IgG3 and IgG4 were measured by
      ELISA. The IgG subclass was also examined retrospectively in sera collected from
      20 patients previously proven to have duodenal ulcer (DU). RESULTS: The results
      of histological examination and IgG serology showed 35 subjects to be H. pylori
      negative and 48 to be H. pylori positive. Of the 48 H. pylori positive subjects,
      25 were diagnosed with functional dyspepsia (FD), 14 with current DU and 9 with
      evidence of past DU. Significantly higher levels of IgG2 antibodies were found in
      patients with DU as compared with patients with FD (P < 0.01). In addition,
      significantly higher IgG3 subclass antibody levels were associated with chronic
      inflammatory cells in the body (P < 0.05) and active inflammatory cells in the
      transitional zone (P < 0.01). A significantly increased level of IgG1 antibodies
      was associated with lower levels of colonization in the gastric antrum.
      CONCLUSION: The results of this study suggest that the IgG subclass response in
      subjects infected with H. pylori may be a marker of DU disease as well as
      increased levels of inflammation.

PMID- 11252408
TI  - Intestinal disaccharidase deficiency without villous atrophy may represent early
      celiac disease.
AB  - BACKGROUND: Intestinal disaccharidase activities are decreased in untreated
      celiac disease and also in other conditions without villous atrophy. Of 908
      patients examined for suspected malabsorption, 37 (4.1%) had generalized
      disaccharidase deficiency without villous atrophy. The aim was to determine if
      generalized disaccharidase deficiency without villous atrophy represented latent
      celiac disease. METHODS: Case notes and histology of the 37 patients were
      reviewed. History and blood investigations including antigliadin and endomysial
      antibodies were checked. Where celiac disease was suspected, endoscopic duodenal
      biopsies for histology and disaccharidase estimation were repeated. RESULTS: Of
      the initial 37 patients, 6 patients had had repeat endoscopic biopsies; one
      having celiac disease. A further 18 patients were reviewed. The remainder
      declined further investigation. Eight had repeat endoscopic duodenal biopsies;
      one had celiac disease. Two with positive celiac serology also had enteroscopy
      with jejunal biopsies; both had celiac disease. CONCLUSIONS: At least 11% of
      patients with generalized disaccharidase deficiency without villous atrophy
      develop celiac disease. Enteroscopic biopsies from distal duodenum and proximal
      jejunum should be considered as the next investigation if endomysial or
      antigliadin antibodies are positive.

PMID- 11252407
TI  - GLP-1 inhibits gastric emptying of water but does not influence plasma.
AB  - BACKGROUND: Glucagon-like peptide-1 (GLP-1) has been shown to inhibit gastric
      emptying of a caloric load but the effect on a non-caloric load is unknown.
      METHODS: Seven healthy men were studied after an over-night fast. Thirty min
      before the intake of 330 ml radioactively labeled water either GLP-1 (0.75
      pmol/kg/min) or saline was administered intravenously and continued for 75 min.
      Scintigraphic gastric emptying was performed for 45 min and plasma samples were
      obtained for analysis of vasopressin, sodium, osmolality, GLP-1, insulin, and
      glucose. In addition, electric field stimulation of human gastric muscle strips
      was done. RESULTS: The median (range) percent water retained in the stomach, 45
      min after intake of water, was 96% (68%-98%) and 12% (2%-42%) (P = 0.02) during
      infusion of GLP-1 and saline, respectively. Additionally, GLP-1 did not affect
      basal tone or contractile response of gastric muscle strips to electric field
      stimulation or acetylcholine (ACh). There was no change in plasma concentrations
      of vasopressin, sodium, or plasma osmolality during GLP-1 compared to saline
      infusion. CONCLUSION: GLP-1 has a profound inhibitory effect on the gastric
      emptying of water in man, but no short-term effect on water homeostasis. No
      effect was seen on contractility of gastric muscle strips suggesting an indirect
      action on gastric emptying.

PMID- 11252410
TI  - Release of mast cell tryptase from human colorectal mucosa in inflammatory bowel
      disease.
AB  - BACKGROUND: Histologic detection of mast cells cannot adequately reflect their
      function and state of activation, since degranulated mast cells may escape from
      histologic assessment. To better define the role of mast cells in inflammatory
      bowel disease, the spontaneous secretion of mast cell tryptase, a highly mast
      cell specific protease, was measured from colorectal samples. METHODS: After
      detection of the initial basal tryptase release, gut mucosal samples were
      incubated in a modified Hanks/RPM1 medium using a mucosa oxygenation system.
      Spontaneous tryptase secretion from 153 viable samples of 22 controls, 30
      patients with Crohn disease (CD) and 19 with ulcerative colitis (UC) was followed
      over 4 h. Tryptase was measured by radioimmunoassay. RESULTS: The rates of the
      initial basal tryptase release revealed that mast cell activation occurs during
      active inflammation in CD and UC. While the time course of tryptase release was
      similar in all three groups, spontaneous tryptase secretion (over 4 h) was found
      to be significantly enhanced and prolonged only in UC (P < 0.01 compared to
      controls), but not in CD. CONCLUSIONS: This study provides clear evidence from
      viable endoscopic colorectal samples that mast cell mediators were secreted
      during active inflammation in CD and UC. However, the extent of mast cell
      involvement and activation differs considerably between CD and UC. Significantly
      increased rates of tryptase secretion were found both in non-inflamed and
      inflamed tissue of UC, indicating that mast cell involvement is a typical feature
      of UC.

PMID- 11252409
TI  - Increased rectal nitric oxide in coeliac disease after local challenge with
      gluten.
AB  - BACKGROUND: Coeliac disease is an inflammatory disorder characterized by
      reversible atrophy of small intestinal villi following the ingestion of gluten.
      Earlier studies indicate that the inflammatory response to gluten may occur also
      very distally in the gastrointestinal tract. The aim of this study was to
      evaluate whether rectal challenge with gluten would trigger an increased local
      production of the gas nitric oxide (NO), a novel marker of intestinal
      inflammation. METHODS: Rectal challenge with partially digested gluten was
      performed in 20 patients with treated coeliac disease and in 13 healthy controls.
      Luminal levels of NO were measured in the rectum at 0, 8 and 24 h using a
      chemiluminescence technique. RESULTS: In patients with coeliac disease mean
      rectal NO increased from 235+/-90 parts per billion (ppb) at 0 h to 4965+/-1653
      ppb at 24 h (P < 0.005). In the control group there was no significant increase.
      One control subject responded with high NO levels at 24 h and the same individual
      tested positive for anti-endomysium IgA antibodies. Subsequent duodenal biopsing
      showed substantial villusatrophy. CONCLUSIONS: Rectal challenge with gluten
      results in increased luminal levels of NO in a group of patients with treated
      coeliac disease. Further studies are needed to evaluate the role of NO in coeliac
      disease and the potential usefulness of rectal NO measurements in aiding
      diagnosis of this intestinal disorder.

PMID- 11252411
TI  - Changes in distribution of three isoforms of nitric oxide synthase in ulcerative
      colitis.
AB  - BACKGROUND: Nitric oxide (NO) has an important role both in normal physiology and
      pathological events of the colon. Our aim was to study possible changes of the
      three nitric oxide synthases in ulcerative colitis (UC). METHODS: Tissue samples
      from normal colon and least and moderately affected regions of ulcerative colitis
      colon were obtained at surgery and immunostained for NOS-1, NOS-2, NOS-3, and GAP
      43, a marker of nerve fibers. Quantitative analysis of NOS-1 immunoreactivity was
      performed on the circular muscle layer. RESULTS: NOS-1-immunoreactive fibers in
      the muscularis mucosae disappeared in least affected and moderately affected UC
      colon. Quantitative analysis of NOS-1-immunoreactive nerve fibers in the circular
      muscle showed no differences between normal and diseased colon. NOS-2
      immunoreactivity appeared apically in the epithelial cells. In normal colon some
      specimens showed immunoreactivity in lower parts of crypts. NOS-2
      immunoreactivity increased according to the severity of UC. NOS-3
      immunoreactivity was exclusively localized in the vascular endothelium. The
      difference in NOS-3 staining intensity between the lamina propria and submucosa
      observed in normal tissue disappeared in moderately affected UC colon. The number
      of NOS-3-immunoreactive vascular profiles increased in the lamina propria of UC
      colon. CONCLUSIONS: All three NOS isoforms show specific changes in UC colon.

PMID- 11252413
TI  - Anti-Saccharomyces cerevisiae antibodies in inflammatory bowel disease: a family
      study.
AB  - BACKGROUND: Antibodies to Saccharomyces cerevisiae (ASCA) have been described as
      specific markers for Crohn disease (CD). The reason for this disease specific
      generation of antibodies is not clear. Therefore, a family study was performed to
      evaluate whether the antibody production was due to genetic or environmental
      factors. METHODS: Seventy-one patients with CD, 25 patients with ulcerative
      colitis (UC), their 282 first-degree relatives, and 32 spouses were included. As
      controls, 43 sera from healthy persons and 69 sera from patients with various
      autoimmune disorders were tested for ASCA by indirect immunofluorescence and
      ELISA. RESULTS: ASCA were detected in 68% of the patients with CD and in none of
      the controls, UC patients included. Forty-eight (25%) first-degree relatives of
      patients with CD were ASCA-positive. ASCA status of relatives was not related to
      the fact whether these persons lived in the same household with the patients or
      not. However, one of the spouses of CD patients (4%) was found to be ASCA
      positive and the antibody was also found in 5 (6%) of the relatives of UC
      patients. CONCLUSIONS: ASCA are specific markers for CD. Since these antibodies
      are found in 25% of first-degree relatives, the generation of ASCA may be mainly
      related to genetic influences although environmental factors may also play a
      certain role.

PMID- 11252412
TI  - Increased response of blood eosinophils to various chemotactic agents in
      quiescent Crohn disease.
AB  - BACKGROUND: The number of eosinophils is increased in the mucosae of the
      digestive and the respiratory tracts in Crohn disease, even clinically quiescent.
      The mechanisms underlying this panmucosal eosinophilia are unknown. METHODS: The
      response of blood eosinophils to various chemotactic agents was assessed in 15
      patients with clinically quiescent Crohn disease. The results were compared with
      15 healthy controls. After purification, eosinophils were placed in Boyden
      microchambers and the chemotactic effect of PAF (10(-7) M), RANTES (50 ng/ml), IL
      5 (0-20 ng/ml), IL-8 (0-50 ng/ml), Eotaxin (0-50 ng/ml) was evaluated. The number
      of eosinophils in induced sputum of these Crohn disease patients and controls was
      also assessed and the correlation between chemotaxis and eosinophil count in
      induced sputum was studied. RESULTS: PAF and RANTES induced a chemotactic effect
      both in Crohn disease patients and controls. The chemotactic index was
      significantly higher in Crohn than controls for PAF (2.09+/-0.24 versus 1.37+/
      0.14; P < 0.05) but not RANTES. With IL-5, IL-8 and Eotaxin, there was no
      detectable chemotactic effect in controls while in Crohn, we observed a
      significant dose-dependent chemotactic effect. Furthermore, with Eotaxin 50
      ng/ml, the chemotactic index was significantly higher in Crohn disease patients
      than controls (2.42+/-0.18 versus 1.56+/-0.28; P < 0.05). A significant increase
      in sputum eosinophil count and a significant decrease in sputum macrophage count
      in Crohn disease were observed. However, there was no correlation between
      eosinophil chemotaxis and sputum eosinophil count in individual patients.
      CONCLUSION: There is an increased response of blood eosinophils to various
      chemotactic agents, mainly PAF and Eotaxin, in clinically quiescent Crohn
      disease. This may participate in the mucosal infiltration by eosinophils in this
      disease.

PMID- 11252414
TI  - Fecal excretion of calprotectin in colorectal cancer: relationship to tumor
      characteristics.
AB  - BACKGROUND: The aim of this study was to evaluate fecal calprotectin in patients
      treated for colorectal cancer. Furthermore, the changes in fecal calprotectin
      concentration from before to after surgery were investigated. METHODS: In 155
      patients with newly diagnosed colorectal cancer, two spot samples were taken from
      the same feces on two consecutive days. RESULTS: Three ways of evaluating
      calprotectin excretion were compared, (1st spot 1st stool; maximum of 1st spot
      1st stool and 2nd spot 1st stool; maximum of 1st spot 1st stool and 1st spot 2nd
      stool) and gave similar results with median fecal calprotectin values 47 mg/l, 52
      mg/l and 54 mg/l, respectively. Median calprotectin concentration did not differ
      significantly between different tumor stages, although the levels were slightly
      lower in Dukes stage A tumor than in the rest of the stages. Neither were there
      any differences in the concentrations related to the localization, size or the
      histological grading of the carcinoma. As the currently used cut-off level for
      fecal calprotectin is 10 mg/l, 87% of all patients had elevated fecal
      calprotectin. Seventy-nine percent of the patients had levels above 15 mg/l and
      74% had levels above 20 mg/l (1st spot 1st stool). In patients who delivered
      fecal samples after the operation the calprotectin value fell significantly from
      a preoperative median value of 45 mg/l to 14 mg/l after the resection.
      CONCLUSIONS: The majority of patients with colorectal cancer have increased fecal
      concentration of calprotectin. One single fecal spot seems to be sufficient for
      determination of the calprotectin level. Measurement of fecal calprotectin may
      possibly become of value as a marker for colorectal cancer, although
      calprotectin, similar to fecal occult blood (FOB) tests, is a non-specific test
      for colorectal pathology, also being elevated in inflammatory bowel diseases.
      Further investigation of its specificity is therefore needed.

PMID- 11252416
TI  - Common bile duct stenosis in complicated chronic pancreatitis.
AB  - BACKGROUND: Common bile duct stenosis (CBDS) is one of the most frequent and
      serious complications in patients with chronic pancreatitis. Due to improved
      diagnostic tools, the frequency of CBDS seems to occur more frequently,
      nevertheless the prevalence varies widely because of different selection
      criteria. METHODS: Between April 1982 and October 1996, 323 patients with chronic
      pancreatitis and inflammatory mass in the head of the pancreas (IMH) (286
      patients) or CBDS alone (37 patients) were operated. Patients' data including US,
      CT, ERCP, endocrine and exocrine function tests were documented prospectively.
      Dividing patients into groups with and without CBDS, clinical data were
      comparable concerning distribution of sex, age, etiology of the disease and
      clinical feature. RESULTS: Regarding the subgroup of 286 patients with
      inflammatory mass in the head of the pancreas (IMH), 154 patients (51%) showed
      radiological proved CBDS; out of this group, 82 patients (57%) revealed
      cholestasis and 37 patients (26%) had one or several periods of jaundice. By
      means of ERCP, 104 patients (72%) revealed short stenosis of the common bile duct
      (CBD) (<2 cm). No significant differences could be found in terms of morphologic
      alterations like pancreatic main duct stenosis, pseudocysts, duodenum stenosis,
      vascular obstruction. Ten patients (7%) in the group with CBDS and 13 patients
      (9%) in the group without CBDS had cancer in the pancreatic head. Concerning the
      endocrine function, the group of patients with CBDS had a significantly elevated
      rate of impaired glucose metabolism (IGT or IDDM) compared to the group without
      CBDS (60% versus 38%; P < 0.003). These results demonstrate that patients with
      IMH bear the risk of developing a stenosis of the CBD even before they become
      symptomatic with cholestasis or jaundice. CONCLUSION: Due to the elevated
      morbidity and the significantly deteriorated endocrine function, patients of this
      group are candidates for early surgical treatment.

PMID- 11252415
TI  - Tobacco smoking increases the risk for gastric adenocarcinoma among Helicobacter
      pylori-infected individuals.
AB  - BACKGROUND: The importance of tobacco smoking and Helicobacter pylori infection
      as risk factors in the development of gastric carcinoma was investigated through
      multivariate conditional logistic regression analysis in a nested case-control
      study. METHODS: Blood samples and a questionnaire on smoking habits were
      collected from a cohort of 32,906 city residents during a health screening
      programme from 1974 to 1992. Fifty-six cases of gastric cancer and 224 matched
      controls were selected. The mean interval between screening and cancer diagnosis
      was 5.7 years. H. pylori infection was determined by IgG-serology. Occupation
      categorized into blue-collar workers, white-collar workers, self-employed and
      unknown occupation was included in the statistical analysis as an indicator of
      socio-economic status. RESULTS: The proportion of current smokers was 61% among
      gastric cancer cases, versus 41% among controls. H. pylori seropositivity was
      present in 82% of the cases and 49% of the controls. In a multivariate model
      current smokers had an odds ratio (OR) of 2.2 (95% confidence interval (CI): 1.2
      4.2). With different levels of tobacco consumption, smoking less than 20 g
      tobacco each day gave the OR of 2.1 (95% CI: 0.98-4.4), and the OR when smoking
      more than 20 g tobacco per day was 2.5 (95% CI: 1.1-5.6). The OR of H. pylori
      infection was 5.0 (95% CI: 2.2-11.2). Among H. pylori-seropositive citizens,
      current smoking was associated with an increased risk of 2.3 (95% CI: 1.1-4.7)
      compared with non-smoking H. pylori-positive persons. CONCLUSIONS: Tobacco
      smoking and H. pylori are both risk factors in the development of gastric cancer,
      and tobacco smoking is still a risk factor among H. pylori-infected individuals.
      The risk of gastric cancer among H. pylori-infected current smokers is 11 times
      that of non-infected individuals not currently smoking.

PMID- 11252417
TI  - Yersinia enterocolitica infection with multiple liver abscesses uncovering a
      primary hemochromatosis.
AB  - A 60-year-old man, although treated with antibiotics, suffered from a severe
      pyrexial illness of unknown origin, weight loss and intermittent abdominal pain.
      There was no history of diarrhea or common infections. Computed tomography and
      ultrasound imaging showed uncharacteristic multiple small lesions of the entire
      liver parenchyma. These lesions were histologically pyogenic abscesses. In
      addition, an unexpected, pronounced accumulation of iron pigment in hepatocytes
      and second degree fibrotic changes of the liver were detected. Serum iron and
      serum transferrin were low, but serum ferritin concentration and transferrin
      saturation were increased to the maximum. The demonstration of the cysteine-282
      tyrosine mutation confirmed underlying primary hemochromatosis. Bacteriological
      cultures of the abscess material yielded Yersinia enterocolitica serotype O:3,
      while stool and blood cultures were negative. Antibiotic therapy with
      piperacillin/tazobactam and tobramycin was successful within a few days. A repeat
      CT scan and ultrasound imaging demonstrated complete regression of the pathologic
      liver morphology. The patient was discharged and treated with an orally
      administered fluoroquinolone for an additional 6 months. After this time the
      patient had no morphological residues of the infection except one enlarged lymph
      node near the portal vein but still was so weak that he was unable to work again.
      In conclusion, severe septic forms of yersiniosis are mainly found in patients
      with iron overload, due to a handicapped iron metabolism of the Yersinia
      bacteria. Mortality is high despite treatment.

PMID- 11252418
TI  - Swelling and bony erosion of the thumb in a 40-year-old-man.

PMID- 11252419
TI  - Study of immunotropic activities of Bacillus subtilis as the basis of anti
      scleroma probiotics.
AB  - Presence of influence of Bacillus subtilis during peroral and parenteral
      administration upon the laboratory animals' immune system has been studied.
      Absence of immuno-depressing action of the bacillus culture under study has been
      presented with the help of assessment tests on the humoral response to the thymus
      dependent antigen: creation of the antibodies, and the delayed-onset
      hypersensitivity reaction. An insignificant stimulating effect has been revealed
      under execution of the reaction of the delayed-onset hypersensitivity as a result
      of B. subtilis application. The obtained data confirm the prospects of
      application of the B. subtilis strain as a basis of the anti-scleroma probiotics.

PMID- 11252421
TI  - From paperwork to patient care.

PMID- 11252422
TI  - Telemedicine offers promise to long-term care.

PMID- 11252420
TI  - Bankrupt chains regrouping as climate improves.

PMID- 11252423
TI  - Computers open new universe of training options.

PMID- 11252424
TI  - Software supplier guide.

PMID- 11252425
TI  - It's time to get moving on HIPAA.

PMID- 11252426
TI  - Is your activities program up to snuff?

PMID- 11252427
TI  - Care with a distinctly human touch.

PMID- 11252428
TI  - [Crataegus in heart failure and coronary heart disease. What is the value of this
      additional medication?].

PMID- 11252429
TI  - Domestic violence and physician liability.

PMID- 11252430
TI  - Caveat doctor! Medical discount cards could burn you.

PMID- 11252431
TI  - A doctor's unique living will.

PMID- 11252432
TI  - The final word--almost--on self-referral.

PMID- 11252433
TI  - Has capitation reached its high-water mark?

PMID- 11252434
TI  - Go on rounds--in a hospitalist's shoes. Interview by Neil Chesanow.

PMID- 11252435
TI  - Plug the gaps in your insurance policies.

PMID- 11252436
TI  - Would your new associate make a good partner? Try this test.

PMID- 11252437
TI  - Helping the addicted: "He sleeps with his beeper at his side.".

PMID- 11252438
TI  - Creating a "safe space" for the patient.

PMID- 11252439
TI  - Making kids do chores can be a labor of love.

PMID- 11252440
TI  - Guard your genetic data from those prying eyes.

PMID- 11252441
TI  - For safe biking, stay sober and stay off the sidewalk.

PMID- 11252442
TI  - Pregnant and panicked about pills? Call for advice.

PMID- 11252443
TI  - Compromise depends on where you sit.

PMID- 11252444
TI  - A moving target: financing Medicare for the future.
AB  - Since 1997, there has been a steady downward trend in projected Medicare spending
      as a share of the gross domestic product (GDP), substantially improving the long
      run outlook for Medicare. But even with improvements in outlook, the required
      share of GDP will rise by more than 70%, and the question remains as to who will
      pay for Medicare in the future. This report examines a limited set of tax options
      and a flat beneficiary premium to illustrate the size of contributions necessary
      to achieve several different goals, and to explore the difference that multiple
      years of projections can make on these requirements.

PMID- 11252446
TI  - The cost effectiveness of post-acute care for elderly Medicare beneficiaries.
AB  - This study used a novel method to examine the cost effectiveness of post-acute
      care (PAC) in different settings. The analysis found that home health care was
      more cost effective than PAC in skilled nursing facilities (SNFs) or
      rehabilitation facilities. The cost effectiveness for home health care was also
      more favorable relative to being home without formal care. Post-acute care in
      SNFs was not cost effective compared to being home without formal care. The cost
      effectiveness analysis showed mixed support for PAC in rehabilitation facilities.
      These results, and the use of cost-effectiveness analysis in general, provide a
      basis for a more efficient Medicare reimbursement system for PAC.

PMID- 11252445
TI  - Long-term care insurance underwriting: understanding eventual claims experience.
AB  - Little is known about the accuracy of medical underwriting for long-term care
      insurance. The lack of data on claims experience continues to be an obstacle in
      testing the ability of medical underwriting to identify above average financial
      risks. This study used actual claims data to simulate medical underwriting and to
      examine the risk, duration, and timing of nursing home use for people with
      conditions that are uninsurable. The results show that at least one older person
      in seven who is rejected for long-term care insurance due to underwriting may not
      represent greater financial risk to insurers than do those who are accepted.

PMID- 11252447
TI  - The structure and enforcement of health insurance rating reforms.
AB  - Requiring health insurers to cover everyone who applies regardless of health
      status--an approach called "guaranteed issue"--is severely hampered without
      accompanying rating restrictions that keep insurance affordable for higher-risk
      people. The degree of rating flexibility also determines how much insurers can
      continue to compete based on their skills at risk selection, and how well they
      can counter adverse selection. Therefore, the structure and enforcement of rating
      reforms are essential to how insurance market reforms function. Based on an in
      depth qualitative study in seven states with insurers, agents, and regulators,
      this article explains the factors that determine the stringency of rating
      reforms, and details how various aspects of rating restrictions can be used
      strategically to engage in greater risk segmentation than first appears possible.
      The article concludes by reflecting on the appropriate degree of complexity in
      rating rules, and it offers recommendations for crafting rating reforms that
      avoid unintended consequences.

PMID- 11252448
TI  - How managed care plans contribute to public health practice.
AB  - Growth in managed care enrollment potentially creates incentives for health plans
      to become involved in public health activities, such as health promotion and
      disease prevention interventions, and care for vulnerable populations. Using
      cross-sectional data from 60 diverse markets, this study explores the extent to
      which health maintenance organizations (HMOs) form cooperative alliances with
      local public health agencies to perform such activities. Results from
      multivariate models suggest that the incentives for cooperation vary
      substantially with health plan ownership and market structure. In view of recent
      HMO industry trends, these findings raise questions about the ability of
      alliances to integrate the practice of public health and medicine on a broad
      national scale, as some proponents suggest they do.

PMID- 11252449
TI  - Association of market, mission, operational, and financial factors with
      hospitals' level of cash and security investments.
AB  - Using a resource dependency framework and financial theory, this study assessed
      the market, mission, operational, and financial factors associated with the level
      of cash and security investments in hospitals. We ranked hospitals in the study
      sample based on their cash and security investments as a percentage of total
      assets: hospitals in the high cash/security investment category were in the top
      25th percentile of all hospitals; those in the low cash/security investment group
      were in the bottom 25th percentile. Findings indicate that high cash/security
      investment hospitals are under either public or private nonprofit ownership and
      have greater market share. They also serve more complex cases, offer more
      technology services, generate greater profits, incur a more stable patient
      revenue base, and maintain less debt.

PMID- 11252450
TI  - State legislation and the use of complementary and alternative medicine.
AB  - There are increasing attempts at the federal and state levels to change
      regulations for complementary and alternative medicine (CAM). We use data from a
      new survey of about 10,000 individuals to examine CAM use and insurance coverage
      and their relationship to state regulations. We find that insurance mandates to
      cover CAM providers are significantly associated with increased coverage of CAM,
      but not with increased use of CAM providers. Liberalization of physician
      licensure to practice CAM is associated with significantly increased CAM use, as
      are practice laws authorizing nonphysician CAM providers. In states with multiple
      CAM practice laws, insurance coverage for CAM visits among users is significantly
      lower than in states without CAM practice laws.

PMID- 11252451
TI  - The HIV/AIDS Prevention Program Archive (HAPPA): a collection of promising
      prevention programs in a box.
AB  - This article describes the methods used and findings obtained in establishing the
      HIV/AIDS Prevention Program Archive (HAPPA), a collection of effective HIV/AIDS
      prevention programs in a box. The HAPPA collection builds on a previously
      established collection of 13 effective HIV/AIDS/sexually transmitted disease
      (STD) prevention programs for adolescents known as PASHA, the Program Archive on
      Sexuality, Health, & Adolescence. Together, the HAPPA and PASHA collections
      provide a rich source of 23 promising programs designed to prevent the spread of
      HIV/AIDS. The HAPPA and PASHA programs are available for use by communities,
      schools, family planning clinics, STD clinics, mental health centers, and drug
      rehabilitation centers throughout the country.

PMID- 11252452
TI  - Building strong linkages across the HIV prevention continuum: the practical
      lessons learned from a comprehensive evaluation effort in Minnesota.
AB  - This article describes practical lessons learned from an evaluation of a
      continuum of HIV prevention efforts and is intended to assist other states in
      strengthening their own HIV prevention evaluation activities. In 1996 Minnesota
      launched several evaluation activities and began to examine how they could be
      linked across the HIV prevention continuum. Although each evaluation activity
      generated its own findings, this article examines the challenges faced and the
      solutions created when integrating these findings into the original steps of the
      HIV prevention continuum. Key points are highlighted to guide HIV professionals
      in their endeavors to develop an integrated approach to evaluation and to
      establish clear and logical linkages across the HIV prevention continuum.

PMID- 11252453
TI  - Variation in health and risk behavior among youth living with HIV.
AB  - Lifetime and current health practices and risk behaviors were examined among 350
      youth living with HIV (YLH) aged 14-23 years from four AIDS epicenters (72.6%
      male; 26.2% African American, 36.9% Latino). YLH were relatively healthy (M CD4
      cells = 499), had used substantial health care and were satisfied with the care.
      YLH's sexual and substance-use histories indicated substantial HIV related risk
      acts: the median number of lifetime partners was 25 with only 8% using condoms
      consistently; 14.9% had injected drugs, and 61.2% had used hard drugs. Compared
      with females, males had more lifetime and recent sexual partners and had used
      more drugs. Youth who were recently sexually active (81.3%) had multiple
      partners. Most of the sexually active YLH used condoms consistently (81.6%). YLH
      who were symptomatic or had an AIDS diagnosis were likely to have recently had
      more seropositive sexual partners than the asymptomatic youth. Youth disclosed
      their serostatus to about half of their sexual partners (53.9%). YLH with AIDS
      used fewer hard drugs than those without an AIDS diagnosis. Health and risk
      behaviors of the YLH varied significantly based on their disease stage, gender,
      and ethnicity, suggesting the need for tailoring interventions for subgroups of
      YLH.

PMID- 11252454
TI  - Patterns of use of the female condom after one year of mass marketing.
AB  - The female condom is an effective new contraceptive method that can reduce HIV
      transmission. This study examines use of the female condom after 1 year of its
      mass marketing and compares this with use of the male condom. It is based on exit
      interviews conducted among a random sample of male and female customers visiting
      outlets that sell the female condom. Compared with reported use of the male
      condom, which was five to eight times as high in nonmarital as in marital
      partnerships, reported use of the female condom varied less by partnership type
      (it was twice as high in nonmarital compared with marital partnerships). In
      marital and regular partnerships, use of the female and the male condom increased
      with socioeconomic status (SES). In casual partnerships, use of the male condom
      increased with SES, but use of the female condom was higher for those with lower
      SES. Men reported higher levels of male condom use than women, but there were no
      gender differences in use of the female condom. These findings suggest that the
      largest contribution to HIV protection through use of the female condom may be
      within marital partnerships and among low SES men and women who engage in casual
      sex. The absence of gender differentials in use of the female condom suggests
      that women are able to exert greater control over the use of the female condom
      than they are over the use of the male condom. However, the overall low levels of
      female condom use among relatively affluent persons at outlets that sell the
      female condom indicate that the introduction of the female condom will be
      resource intensive.

PMID- 11252455
TI  - Barriers to condom use: results from a study in Mumbai (Bombay), India.
AB  - The consistent and correct use of condoms coupled with risk reduction education
      strategies, continue to play an important role in the reduction and prevention of
      HIV/AIDS transmission. Therefore understanding and incorporating strategies to
      overcome barriers to condom use in such education and prevention efforts are
      critical. This is particularly necessary in countries such as India, where
      HIV/AIDS has become a serious public health crisis. The current study documents
      and provides preliminary data on the use of condoms, reasons for and barriers to
      condom use, and sources of information about safer sex practices among a sexually
      active adult sample of 49 women and 203 men in Mumbai, India. Despite limitations
      such as the use of a nonrandom sample of participants composed predominantly of
      young, English-speaking males, the study findings provide some insights into the
      importance of and the need to address issues of privacy regarding condom purchase
      and use in India. Most notably, the lack of privacy in stores and the social
      stigma associated with condom use were indicated as the most significant
      barriers. These and other study findings suggest the need to ease the social
      costs and constraints to safe behaviors through increased acceptance of condoms
      and promotion of their consistent use. This could serve as an important means to
      curb the epidemic of HIV/AIDS in India.

PMID- 11252456
TI  - Needle exchange program attendance and injection risk in Providence, Rhode
      Island.
AB  - Needle sharing has long been recognized as a primary route of HIV infection.
      However, recent research has shown that HIV antibody is also detectable in
      injection supplies other than needles. In this study we tested frequency of
      attendance at a Providence, Rhode Island, needle exchange program (NEP) as a
      correlate of injection risk indicators including not just sharing needles but
      also sharing cookers, sharing cotton filters, cleaning the skin before injecting,
      and using bleach as a needle disinfectant. Results showed that drug users who
      attended the NEP less frequently were more likely to report needle sharing, less
      likely to report always cleaning their skin, and more likely to report sharing
      cookers. The Providence NEP is one at which alcohol swabs and cookers are
      distributed along with clean needles. Our results suggest that NEPs represent a
      valuable and underexploited opportunity to promote risk reduction efforts beyond
      the avoidance of needle sharing. NEPs should be distributing risk reduction
      supplies in addition to clean needles and should adopt strategies (e.g., outreach
      and more days/hours of operation) to encourage frequent attendance.

PMID- 11252457
TI  - Effects of a cognitive-behavioral HIV prevention intervention among HIV negative
      male substance abusers in VA residential treatment.
AB  - This investigation compared the effectiveness of a cognitive-behavioral HIV risk
      reduction intervention with a standard care (SC) comparison condition in
      modifying HIV risk related knowledge, beliefs, attitudes, and behavior at 6-month
      and 12-month follow-ups among 149 HIV seronegative males. The two intervention
      conditions were administered while participants were in inpatient alcohol and
      other drug abuse treatment. Global drug abuse severity, as well as injection drug
      abuse, decreased significantly from preintervention to follow-up across
      conditions. There were significant increases in the proportions reporting sexual
      activity and increases in levels of unprotected sex acts between baseline and
      follow-up across conditions. However, no changes in sex risk behavior were found
      among those who reported sexual activity both prior to and after intervention
      across conditions. Participants revealed relatively adequate knowledge regarding
      HIV and HIV risk reduction practices, strong belief in the utility of safer
      practices and in their ability to enact such practices, and relatively strong
      commitment to practice safer sex across conditions at baseline assessment. In
      general, substantial postintervention improvements over baseline levels in these
      areas were not found. Relatively modest changes in sexual self-efficacy and in
      safe-sex guidelines were identified in analyses involving the total sample.
      Exploratory subgroup analysis suggested increases in knowledge and reductions in
      susceptibility and anxiety among those who reported sexual activity both prior to
      and after intervention. Among participants reporting initiation of sexual
      activity after intervention, those receiving SC revealed changes in perceived
      susceptibility and in condom attitudes. A discussion is presented of challenges
      associated with providing meaningful HIV risk reduction intervention when
      baseline levels of sex risk behavior, perceived HIV infection susceptibility, and
      HIV anxiety are only moderate and when initial levels of sexual self-efficacy and
      commitment are relatively high.

PMID- 11252459
TI  - Is a knee brace advantageous after anterior cruciate ligament surgery? A
      prospective, randomised study with a two-year follow-up.
AB  - The aim of this study was to evaluate the use of a knee brace after arthroscopic
      anterior cruciate ligament reconstruction using central third patellar tendon
      autografts. Fifty patients were randomly allocated to two groups. The patients in
      Group A wore a brace for three weeks postoperatively, while the patients in Group
      B were rehabilitated without the use of a brace. Pre-operatively, the groups were
      comparable in terms of age, sex, activity level, knee laxity and muscle strength.
      The follow-up examination was performed by one independent observer. All the
      patients were followed up for a minimum of two years. At the follow-up, there
      were no significant differences between the study groups in terms of the Tegner
      activity level, Lysholm score, IKDC evaluation system, one-leg-hop quotient, KT
      1000 measurements and isokinetic torque. Using the visual analogue scale, the
      patients in Group A evaluated their pain during the first two post-operative
      weeks as 1.0 (0-7), compared with 2.3 (0-9) in Group B (P= 0.04). Furthermore,
      the patients in Group A had a tendency towards fewer problems with swelling,
      haemathrosis and wound leakage during the early post-operative period (P=0.08).
      We conclude that the patients who were rehabilitated with the use of a brace had
      less pain and a tendency towards fewer complications during the early post
      operative period than the patients who were rehabilitated without the use of a
      brace. However, there were no differences in terms of function or knee laxity at
      the two-year follow-up.

PMID- 11252460
TI  - Articular cartilage lesions and anterior knee pain.
AB  - The present case-control study included as cases 24 athletes with anterior knee
      pain, and 17 controls, matching the cases according to gender and age. All cases
      had their most symptomatic knee examined by magnetic resonance imaging (MRI).
      Among controls one knee was chosen for examination at random. The MRI of the
      patella showed articular cartilage lesions in 17 out of 24 cases, whereas among
      the controls 4 out of 17 had articular cartilage lesions. (Odds Ratio 7.9 (95%
      confidence interval 1.9-33)). However, presence of articular cartilage lesions
      was not associated with duration of symptoms or intensity of the anterior knee
      pain. The present study showed a significant positive association between
      presence of articular cartilage lesions in the patella and presence of anterior
      knee pain, but further studies are needed to examine the relationship in detail.

PMID- 11252461
TI  - Evaluation of the reproducibility of the KT-1000 arthrometer.
AB  - The aim of the study was to examine whether the KT-1000 arthrometer was reliable
      when it came to distinguishing between a group of patients with a chronic
      anterior cruciate ligament (ACL) rupture and a group of patients without an ACL
      rupture, and to examine the reproducibility of the examination between two
      experienced examiners. The aim was also to examine whether the KT-1000
      measurements were dependent on whether the patients were awake or under
      anaesthesia. The study comprised 40 patients: Group A consisted of 20 patients
      who had a chronic unilateral ACL rupture and Group B consisted of 20 patients who
      were scheduled for arthroscopy due to knee problems other than an ACL rupture.
      The KT-1000 examination was performed before surgery by two experienced
      physiotherapists (PT I and PT II). PT II subsequently performed a retest of the
      patients under anaesthesia. The mean anterior side-to-side laxity difference
      between PT I and PT II was 0.2 mm in Group A and 1.8 mm in Group B (n.s.,
      P=0.03). The anterior side-to-side measurements of knee laxity revealed
      significant differences between Group A and Group B, independent of who the
      measurements were made by when the patients were awake (PT I P=0.011, PT II
      P=0.001). However, no significant difference (P=0.063) was found when the
      patients were under anaesthesia. The interclass correlation coefficient (ICC)
      between PT I and PT II in Group A was 0.55 (P=0.005) for the anterior side-to
      side laxity, while it was 0.60 (P=0.002) in Group B. There were no significant
      differences within Group A or Group B between the measurements made when people
      were awake compared with those under anaesthesia. The conclusions of the study
      were that the KT-1000 arthrometer was able to distinguish a group of patients
      with an ACL rupture from a group without one. The reproducibility of the KT-1000
      measurements of anterior knee laxity between two experienced examiners was
      considered as fair. Furthermore, the measurements were not dependent on whether
      the patients were awake or under anaesthesia.

PMID- 11252458
TI  - Back pain and radiological changes in the thoraco-lumbar spine of athletes. A
      long-term follow-up.
AB  - From 1996 to 1999, back pain and radiological changes in the thoraco-lumbar spine
      were investigated in 134 former top athletes, representing wrestling, gymnastics,
      soccer and tennis (age 27-39 years) and a group of 28 non-athletes of comparable
      age. This is a long-term follow-up investigation of a previous radiological study
      of the spine with clinical correlation. Despite significantly more radiological
      abnormalities among the athletes, they did not report higher frequency of back
      pain than the non-athletes. A decrease in disc height or new disc height
      reduction in one or more of the intervertebral discs between the two examinations
      correlated significantly with back pain at follow-up.

PMID- 11252462
TI  - Serum creatine kinase level is a poor predictor of muscle function after injury.
AB  - Serum creatine kinase and dorsiflexion torque levels were measured in New Zealand
      White rabbits 1, 2, 7, 14, or 28 days after a single bout of eccentric exercise
      (n=26). No significant correlation was observed between creatine kinase activity
      and torque across time periods (P>0.15) and the regression relationship described
      only about 8% of the experimental variability. These data demonstrate that there
      exists a poor correlation between serum creatine kinase levels and skeletal
      muscle function after eccentric exercise.

PMID- 11252463
TI  - Rehabilitation research in sports medicine.

PMID- 11252464
TI  - Sensorimotor control of knee stability. A review.
AB  - Traditionally, the concept of joint stability considered the displacement (or
      subluxation) of two bones relative to each other as the measurement index, and
      attributed the preservation of such stability in its physiologic range to the
      various ligaments associated with the joint. Although the ligaments are indeed
      the major restraints of any joint, the significant contribution of the
      musculature toward joint stability had been grossly overlooked or neglected until
      the last 15 years. The value and importance of muscular activity in that role
      becomes immediately apparent if one performs even a superficial functional
      comparison of muscles and ligaments. Ligaments are passive viscoelastic
      structures, whereas muscles are dynamic viscoelastic organs. The viscoelastic
      effects of the ligaments are activated and applied strictly upon the geometric
      and kinematic configuration of the joint traversing through its range of motion
      according to fixed force-displacement relationships. The musculature, however,
      can apply passive viscoelastic effects to the joint when not active (passive
      tone) and variable dynamic viscoelastic effects when contracting under voluntary
      or reflexive control, and at any desirable point in the range of motion and in
      response to joint speed, external load, gravity, pain, and so forth, while
      executing the functional objective of the movement set by the individual.
      Preservation of joint stability cannot be ascribed to the ligaments alone, but
      should be considered as a synergistic function in which bones, joint capsules,
      ligaments, muscles, tendons, and sensory receptors and their spinal and cortical
      neural projects and connections function in harmony. The objective of this report
      is to first review the anatomy and physiology of the various mechanoreceptors and
      their neural pathways about the joint, and describe some of the current concepts
      of the reflex arcs elicited by such receptors, with special emphasis on
      biomechanical outcomes relative to stability. The role of the musculature in
      maintaining stability while controlling joint motion is then reviewed, with data
      obtained from experiments performed on humans and animals. Finally, some clinical
      findings from patients with anterior cruciate ligament deficiency using a brace
      that simulates the ligament-muscle functions is described.

PMID- 11252465
TI  - Flexibility and passive resistance of the hamstrings of young adults using two
      different static stretching protocols.
AB  - This investigation determined the effects of a static stretching program with
      different stretching protocols on the flexibility and passive resistance of the
      hamstrings of young adults. Forty healthy subjects (24 males and 16 females) aged
      18 to 30 years were randomly assigned to one of four groups. The two training
      groups underwent static stretch training of the hamstrings either with a four
      week protocol or with an eight-week protocol. The other two groups acted as
      control groups. A significant increase in flexibility of hamstrings was found in
      both of the two training groups (P<0.05). No difference was found in the range of
      motion gained between the two training groups. An increase in passive resistance
      at the corresponding maximal joint angle was only demonstrated in the four-week
      training group (P<0.05). Both protocols are effective in terms of improving
      flexibility of hamstrings. However, if injury is reduced when there is relatively
      lower passive resistance at the end-of-range, then the eight-week training
      regimen would be recommended.

PMID- 11252466
TI  - Stress fractures of the tibia: can personality traits help us detect the injury
      prone athlete?
AB  - One of the few serious drawbacks associated with running is overuse injuries such
      as stress fractures of the tibia, which cause local pain and swelling, often
      resulting in a temporary cessation of training. Whereas some runners rarely
      become injured, others experience recurrent injuries even during fairly short
      periods of time. The aim of the present study was to compare selected personality
      traits in a group of runners who had sustained a previous tibial stress fracture
      (n=17), with a matched group of runners (n=17) who had never experienced stress
      fractures. The results indicated that the injured runners, especially the women,
      scored higher than the non-injured runners did on inventories measuring both the
      Type A behavior pattern and exercise dependency. Since motivation, ambitiousness,
      and competitiveness are integral parts of these inventories, high scoring
      individuals might be part of a high-risk population for running injuries, the
      more so if the individual also feels dependent on regular running for managing
      stress related mood states, which was the case particularly for the injured women
      in the present study. However, the somewhat limited number of runners who had had
      a confirmatory scintigram, which was a criterion for inclusion in the study,
      warrants a cautious interpretation of the results. The findings nevertheless
      suggest that in order to prevent recurrent injuries, health education
      professionals and clinicians ought to focus on conveying the importance of
      detecting precursors of injury, and the subsequent steps which should be taken to
      avoid developing a serious injury.

PMID- 11252467
TI  - Creatine supplementation improves sprint performance in male sprinters.
AB  - The object of this study was to evaluate the effect of creatine (Cr)
      supplementation in well trained male sprinters. The study was performed as a
      single blind test on 18 sprinters at a local competition level. During the last
      two years a substantial part of their training had consisted of a series of
      maximal sprints with short rest periods to improve their fatigue resistance. The
      participants consumed either 20 g Cr+20 g glucose per day (Cr group, n=9) or 40 g
      glucose per day (placebo group, n=9), divided into 4 equal dosages. The effect of
      Cr on sprint performance was evaluated in two tests, 1 x 100 m sprint and an
      intermittent 6x60 m sprint. Cr supplementation increased the 100 m sprint
      velocity (11.68+/-0.27 s vs 11.59+/-0.31 s) and reduced the total time of 6
      intermittent 60 m sprints (45.63+/-1.11 s vs 45.12+/-1.1 s), whereas no changes
      were observed in the placebo group. The sprint velocity was significantly
      increased in 5 out of 6 intermittent 60 m sprints. Venous blood was drawn 5 min
      after finishing the final intermittent 60 m run. Plasma lactate, Cr and serum
      creatinine (Crn) were all increased in the Cr group compared to
      presupplementation values; no changes were observed in the placebo group. The
      improved sprint performance suggests an increased availability of energy
      substrate for performing work, possibly as a result of increased skeletal muscle
      creatine phosphate (PCr).

PMID- 11252469
TI  - Elution, detection, and quantification of polio I, bacteriophages, Salmonella
      montevideo, and Escherichia coli O157:H7 from seeded strawberries and tomatoes.
AB  - This study compared the effect of different physical and chemical treatments of
      strawberries and tomatoes to determine their ability to recover seeded viral and
      bacterial pathogens from produce surfaces. Solutions of salts, amino acids,
      complex media, and detergents were compared as eluants. Phosphate-buffered saline
      (PBS) containing 0.1% Tween 80 eluted the highest number of seeded
      microorganisms. Elution with this defined solution was then compared under
      different conditions of physical agitation. Rotary shaking for 20 min at 36
      degrees C eluted higher numbers of viruses and bacteria than did low- or high
      speed stomaching. Commercially available and laboratory prepared bacteriological
      differential media were compared for their ability to recover and distinguish
      eluted Salmonella Montevideo and Escherichia coli O157:H7 strains from seeded
      produce. The recovery of seeded bacterial pathogens was low when differential
      media containing selective ingredients were used (MacConkey sorbitol agar, XLD
      agar, MacConkey agar). Highest recoveries were obtained on a medium consisting of
      tryptic soy agar supplemented with sodium thiosulfate and ferric ammonium citrate
      compared with selective media that inhibited up to 50% of the growth of the
      eluted microorganisms.

PMID- 11252468
TI  - Evaluation of avian-specific probiotic and Salmonella enteritidis-, Salmonella
      typhimurium-, and Salmonella heidelberg-specific antibodies on cecal colonization
      and organ invasion of Salmonella enteritidis in broilers.
AB  - Salmonella Enteritidis colonizes the intestinal tract of poultry and causes
      foodborne illness in humans. Reduction of Salmonella Enteritidis colonization in
      the intestinal tract of poultry reduces potential carcass contamination during
      slaughter. The purpose of this study was to determine the effect of an avian
      specific probiotic combined with Salmonella Enteritidis-, Salmonella Typhimurium
      , and Salmonella Heidelberg-specific antibodies on the cecal colonization and
      organ invasion of Salmonella Enteritidis in broiler as well as on body weights.
      The treatment group was defined as chicks spray-vaccinated with Avian Pac Plus at
      the hatchery and given Avian Pac Plus for the first 3 days after placement. An
      intermediate treatment was given at 10 and 14 days, 2 days prior to vaccination
      and 2 days postvaccination. All birds were vaccinated with Newcastle disease
      vaccine, La Sota virus (one drop/eye) at 12 days of age. A final treatment was
      given 3 days preslaughter. The control group was defined as chicks not given
      Avian Pac Plus at any time. Six hours after oral administration of the probiotic
      suspension (treatment group) or water (control group) at placement, the chicks
      were challenged with Salmonella Enteritidis. All chickens were orally inoculated
      with 0.25 ml of Salmonella Enteritidis that contained 4 x 10(7) CFU/1.0 ml. Cecal
      colonization and organ invasion were evaluated for Salmonella Enteritidis on days
      0, 1, 3, 7, 10, 17, 24, 31, 38, and 41. The probiotic-treated group had a
      significantly lower concentration of Salmonella Enteritidis cecal colonization at
      days 3, 7, 10, 17, 24, 31, 38, and 41 when compared to the nontreated, control
      group (P < 0.05). Similarly, there was a significant difference (P < 0.05) in the
      isolation of Salmonella Enteritidis from the internal organs (liver and spleen)
      when probiotic-treated and nonprobiotic-treated groups were compared. There was
      no significant difference (P > 0.05) in the mean body weight between the two
      experimental groups at each collection period. These results indicated that a
      combination of Lactobacillus acidophilus, Streptococcus faecium, and Salmonella
      Enteritidis, Salmonella Typhimurium, and Salmonella Heidelberg-Specific
      antibodies have a beneficial effect in reducing the colonization of Salmonella
      Enteritidis in market-aged broilers.

PMID- 11252470
TI  - Expression of red-shifted green fluorescent protein by Escherichia coli O157:H7
      as a marker for the detection of cells on fresh produce.
AB  - Escherichia coli O157:H7 was transformed with a plasmid vector red-shifted green
      fluorescence protein (pEGFP) to express red-shifted green fluorescence protein
      (EGFP) from Aequorea victoria. The EGFP expression among total cells and
      nonviable cells was determined at the cellular level by microscopic observation
      of immunostained and membrane-impermeable, dye-stained cultures, respectively. E.
      coli O157:H7 retained pEGFP during frozen storage at -80 degrees C. The
      percentage of EGFP expression was improved by repeated subculturing, reaching
      83.4 +/- 0.1%, although the fluorescence intensity varied among cells. A low
      percentage of EGFP-expressing cells was nonviable. The percentage of EGFP
      decreased when the culture plate was kept at 4 degrees C, suggesting that some
      cells lost pEGFP during refrigeration. The storage of the culture suspension in
      sterile deionized water at 4 degrees C for 24 h reduced the percentage of EGFP
      expression, indicating that some EGFP was denatured. The application of EGFP as a
      marker for E. coli O157:H7 on green leaf lettuce, cauliflower, and tomato was
      evaluated using confocal scanning laser microscopy. EGFP-transformed cells were
      readily visible under confocal scanning laser microscopy on all produce types.
      The numbers of E. coli O157:H7 cells detected with EGFP were equivalent to those
      detected with immunostaining for green leaf lettuce and cauliflower but less for
      tomato. E. coli O157:H7 attached preferentially to damaged tissues of green leaf
      lettuce and tomato over intact tissue surfaces and to flowerets of cauliflower
      than to stem surfaces. EGFP can serve as a marker to characterize E. coli O157:H7
      attachment on green leaf lettuce and cauliflower but may not be suitable on
      tomato.

PMID- 11252471
TI  - Survival and growth of Escherichia coli O157:H7 inoculated onto cut lettuce
      before or after heating in chlorinated water, followed by storage at 5 or 15
      degrees C.
AB  - This study determined the effects of mild heat and chlorine treatment followed by
      storage for up to 18 days at 5 degrees C or 7 days at 15 degrees C on the
      survival and growth of Escherichia coli O157:H7 inoculated onto fresh-cut iceberg
      lettuce. The efficacy of treatment with 20 ppm chlorine in killing the pathogen
      on lettuce at 50 degrees C was determined. Treatment of lettuce with 20 ppm
      chlorine at either 20 or 50 degrees C did not result in significantly greater
      reductions in populations of E. coli O157:H7 compared to respective treatments in
      water without chlorine. The pathogen steadily decreased in viability on treated
      lettuce throughout subsequent storage at 5 degrees C for 18 days. The population
      increased by 2.3 to 3.2 log10 CFU/g within 2 days, then continued to increase at
      a slower rate through 7 days of storage at 15 degrees C. At 4 and 7 days,
      significantly (alpha = 0.05) higher populations were reached on lettuce that had
      been treated at 50 degrees C, compared to respective samples that had been
      treated at 20 degrees C, regardless of the presence of 20 ppm chlorine in the
      treatment water. Treatment of lettuce with 20 ppm chlorine at 50 or 20 degrees C
      before or after inoculation with E. coli O157:H7 did not have a marked influence
      on behavior of the pathogen during subsequent storage at 5 or 15 degrees C.

PMID- 11252472
TI  - Microscopic observation and processing validation of fruit sanitizing treatments
      for the enhanced microbiological safety of fresh orange juice.
AB  - Studies were conducted to evaluate the infiltration of dye and bacteria into the
      interior of orange fruit and the impact of possible infiltration on achieving a 5
      log microbial reduction during fresh juice processing. Fresh orange fruit were
      treated at the stem end area with dye and either Salmonella Rubislaw or
      Escherichia coli strains expressing green fluorescent protein. Microscopic images
      showed that bacterial contaminants localized at the surface or near surface areas
      that may be sanitized by surface treatments. Dye infiltration was not a reliable
      indicator of bacterial penetration in citrus fruit. To quantify the reduction of
      bacterial contamination, orange fruit were inoculated with E. coli and processed
      with and without hot water treatments. Greater than 5-log reductions were
      achieved in juice extracted from fruit immersed in hot water for 1 or 2 min at 80
      degrees C, in comparison to the E. coli level detected in the control juice
      obtained by homogenization of inoculated fruit.

PMID- 11252473
TI  - Thermal inactivation of stationary-phase and acid-adapted Escherichia coli
      O157:H7, Salmonella, and Listeria monocytogenes in fruit juices.
AB  - The heat resistance of stationary-phase and acid-adapted Escherichia coli
      O157:H7, Salmonella enterica (serotypes Typhimurium, Enteritidis, Gaminara,
      Rubislaw, and Hartford), and Listeria monocytogenes was evaluated in single
      strength apple. orange, and white grape juices adjusted to pH 3.9. The heat
      resistance increased significantly (P < 0.05) after acid adaptation. Salmonella
      had an overall lower heat resistance than the other pathogens. Acid-adapted E.
      coli O157:H7 presented the highest heat resistance in all juices at the
      temperatures tested, with lower z-values than Salmonella and L. monocytogenes.
      The heat resistance (D(60 degrees C)-values) of all three pathogens, assessed in
      tryptic soy broth adjusted to different pH values, increased above pH 4.0. From
      the results obtained in this study, one example of a treatment that will
      inactivate 5 logs of vegetative pathogens was calculated as 3 s at 71.1 degrees C
      (z-value of 5.3 degrees C). Normal processing conditions calculated for hot
      filled, shelf-stable juices achieve a lethality in excess of 50,000 D for all
      three pathogens.

PMID- 11252474
TI  - Heat resistance of an outbreak strain of Listeria monocytogenes in hot dog
      batter.
AB  - The heat resistance of a strain of Listeria monocytogenes responsible for a
      listeriosis outbreak in hot dogs was not higher than the heat resistance of other
      L. monocytogenes strains when tested in tryptic soy broth and in laboratory
      prepared hot dog batter. For the thermal death time experiments, the cells were
      grown to stationary phase or were starved in phosphate-buffered saline, pH 7, for
      6 h at 30 degrees C. Starvation increased the heat resistance of L. monocytogenes
      in broth but not in hot dog batter. D-values in hot dog batter were higher than
      in broth. For the hot dog formulation used in this study, cooking the hot dog
      batter for 30 s at 71.1 degrees C (160 degrees F), or its equivalent using a z
      value of 6 degrees C (11 degrees F), would inactivate 5 logs of L. monocytogenes.

PMID- 11252475
TI  - Microbiological sampling of meat cuts and manufacturing beef by excision or
      swabbing.
AB  - Groups of 25 beef or pork loin primal cuts or of pieces of stored or not stored
      manufacturing beef were sampled by excision and by swabbing with cotton wool,
      sponge, and gauze. Total aerobic counts, coliforms, and Escherichia coli from
      each sample were enumerated. Values for the mean log10, log10 mean, and/or the
      log10 total numbers recovered were calculated for each set of 25 bacterial
      counts. Those statistics indicated that, for product sampled without storage,
      swabbing with cotton wool or sponge recovered about 30%, and swabbing with gauze
      recovered about 10% of the bacteria recovered by excision sampling; but that for
      product sampled after storage, swabbing with cotton wool or sponge recovered
      about 50% and swabbing with gauze recovered about 15% of the bacteria recovered
      by excision sampling. However, the incidences of samples positive for coliforms
      and E. coli were less for stored than for nonstored product with all methods of
      sampling. The findings indicate that the conditions of meat surfaces, the
      handling of product, and the state of the microflora might all affect the numbers
      of bacteria recovered by any sampling technique. Thus, the relationship between
      the numbers recovered by excision or any selected swabbing technique may differ
      for different types of noncomminuted, raw meat product.

PMID- 11252476
TI  - Evaluation of combination treatment processes for the microbial decontamination
      of pork trim.
AB  - Combination treatment processes for the microbial decontamination of pork trim
      were developed and evaluated. Lean pork trim tissue (LPT) and fat-covered pork
      trim tissue (FPT) inoculated with swine feces were treated with intervention
      processes as follows: (i) control (untreated), (ii) water (15 degrees C, 120 s),
      (iii) water followed by lactic acid wash (15 degrees C, 75 s), (iv) combination 1
      (water plus hot water [65.5 degrees C, 15 s] plus hot air [510 degrees C, 60 s]
      plus lactic acid), (v) combination 2 (water plus hot water [82.2 degrees C, 15 s]
      plus hot air [510 degrees C, 75 s] plus lactic acid), and (vi) combination 3
      (water plus hot water [82.2 degrees C, 45 s] plus hot air [510 degrees C, 90 s]
      plus lactic acid). Populations of aerobic bacteria, psychrotrophic bacteria,
      coliforms, Escherichia coli, and lactic acid bacteria were determined before and
      after treatment and at days 2 and 7 of 4 degrees C storage. Regardless of the
      intervention treatment, lower microbial populations were observed on FPT than on
      LPT immediately after treatment and during the 7-day storage period. Both LPT and
      FPT treated with water plus lactic acid, combination 1, combination 2, and
      combination 3 had lower remaining populations of all microbial groups immediately
      after treatment than did water-treated samples. Populations of aerobic bacteria,
      coliforms, E. coli, and lactic acid bacteria on either LPT or FPT did not
      statistically increase during the 7-day storage period. On LPT, populations of
      psychrotrophic bacteria grew during 4 degrees C storage but remained lower at day
      7 on LPT treated by combinations 2 and 3 (2.29 and 1.89 log10 CFU/cm2,
      respectively) than on LPT treated with water (4.07 log10 CFU/cm2) or water plus
      lactic acid (3.52 log10 CFU/cm2). Populations of psychrotrophic bacteria remained
      below detectable levels throughout the 7-day storage on FPT treated with water
      plus lactic acid or any of the three combination treatments. Treatment of pork
      trim with any of the combination treatments significantly (P < 0.05) affected the
      color and emulsion stability of the ground pork. Water and water plus lactic acid
      were the most favorable treatments in reducing microbial populations on pork trim
      without affecting the quality attributes of the ground pork.

PMID- 11252477
TI  - Microbiological quality and safety of quahog clams, Mercenaria mercenaria, during
      refrigeration and at elevated storage temperatures.
AB  - The effects of storage temperatures and times on the microbiological quality and
      safety of hard-shelled quahog clams (Mercenaria mercenaria) were examined.
      Samples were stored at four different incubation temperatures (3.3, 7.2, 10.0,
      and 12.8 degrees C) for a period of 3 weeks, following their harvest from summer
      growing waters (> or = 27 degrees C) and winter waters (< or = 4 degrees C).
      Clams were analyzed for two naturally occurring pathogens, Vibrio
      parahaemolyticus and Vibrio vulnificus. During the summer, V. parahaemolyticus
      was isolated from 56% of the stored samples, with the highest concentration,
      6,100/g, occurring on day 12 at 12.8 degrees C. Also, during the summer, V.
      vulnificus was isolated from 11% of the stored samples, with the highest
      concentration of 1,500/g occurring on day 15 at 7.2 degrees C. No Vibrio spp.
      were detected during the winter. During summer storage, aerobic mesophilic counts
      on plate count agar (PCA) containing 2% NaCl ranged from 10(4) to 10(8) CFU/g,
      and during storage of the winter samples, aerobic mesophilic PCA (with added
      NaCl) counts ranged from <100 to 10(4) CFU/g. Comparatively, summer storage
      mesophilic counts on PCA containing no added NaCl ranged from <100 to 10(5)
      CFU/g, and for the winter samples the range was <100 to 10(2) CFU/g. Coliform and
      fecal coliform counts ranged from <0.3 to 61.1/g and <0.3 to 24.4/g,
      respectively. There was no statistical correlation between the length of storage
      or the temperature of incubation and the presence of V. parahaemolyticus, V.
      vulnificus, coliforms, or fecal coliforms. However, storage time and incubation
      temperature affected the PCA counts (P < or = 0.05) in quahog clams.

PMID- 11252478
TI  - Rapid identification of Bacillus cereus based on the detection of a 28.5
      kilodalton cell surface antigen.
AB  - Conventional procedures for the identification of suspect Bacillus cereus
      isolated on mannitol-egg yolk-polymyxin (MYP) agar may need several days. To
      facilitate the identification of the bacterium, an enzyme-linked immunosorbent
      assay (ELISA) was developed. The assay was based on the detection of a 28.5-kDa
      cell surface antigen of B. cereus. Bacterial colonies grown on MYP agar or
      nutrient agar were suspended in phosphate-buffered saline (pH 7.2) containing
      0.1% Teepol. The cell suspensions were heated at 100 degrees C for 5 min and
      added to the microtiter plates coated with antibodies against the 28.5-kDa
      antigen. After washing, the same antibodies labeled with horseradish peroxidase
      were used as secondary antibodies to reveal the signal of antigen-antibody
      reaction. For 38 strains of B. cereus and 127 strains of non-B. cereus bacteria
      (including 79 isolates of Bacillus spp.) tested, the sensitivity and specificity
      of the ELISA were 100 and 88.2%, respectively. Strains producing false-positive
      results were members of the B. cereus group (i.e., Bacillus anthracis, Bacillus
      mycoides, and Bacillus thuringiensis), which are genetically and biochemically
      similar to B. cereus. Similar ELISA results were obtained by using antibodies
      against another cell surface antigen with a molecular mass of 20 kDa. If members
      of the B. cereus group were recognized as a single species, the sensitivity and
      specificity of the ELISA were 100 and 99.1%, respectively. The ELISA could be
      used as a rapid method for presumptive identification of B. cereus grown on MYP
      agar.

PMID- 11252479
TI  - Evaluation of a 5'-nuclease (TaqMan) assay for the detection of virulent strains
      of Yersinia enterocolitica in raw meat and tofu samples.
AB  - Culture methods for detecting virulent Yersinia enterocolitica require selective
      enrichment and a series of confirmatory tests that are time-consuming, costly,
      and laborious. The objective of this study was to evaluate a fluorogenic 5'
      nuclease assay for detecting the enterotoxin yst gene of virulent Y.
      enterocolitica in pure cultures, inoculated ground pork samples, and naturally
      contaminated food samples. These results were then compared with "gold standard"
      methods recommended by the U.S. Food and Drug Administration in the
      Bacteriological Analytical Manual for detecting pathogenic Y. enterocolitica. The
      5'-nuclease assay was able to identify the organism in 100% of the repetitions
      when 10(2) CFU/ml or more organisms were present in pure cultures and 10(3) CFU/g
      or more organisms were present in ground pork. Similar recovery efficiency on
      cefsulodin-irgasan-novobiocin (CIN) agar plates was only evident when 10(5)
      CFU/ml or more organisms were present in pure culture and 10(6) CFU/g or more
      organisms were present in inoculated ground pork. The 5'-nuclease assay indicated
      a contamination rate of 35.5% (94/265) in various meats and tofu, whereas the CIN
      plating method indicated a contamination rate of 28.3% (75/265). This resulted in
      100% sensitivity and 64.5% specificity for the 5'-nuclease assay when compared
      with the standard culture recovery method. Only 75% (60/80) of the Yersinia spp.
      isolated on CIN was identified as containing a virulence plasmid by
      autoagglutination and crystal violet binding tests. These results indicate that
      the true rate of contamination of virulent Y. enterocolitica in pork and other
      processed meats and foods is being underestimated using current detection
      methods. This study demonstrates the potential of the 5'-nuclease assay for
      rapidly and specifically detecting virulent Y. enterocolitica in processed foods
      with the added advantage of being an automated detection system with high
      throughput capability.

PMID- 11252480
TI  - Improved agar diffusion method for detecting residual antimicrobial agents.
AB  - The improved agar diffusion method for determination of residual antimicrobial
      agents was investigated, and the sensitivities of various combinations of test
      organisms and assay media were determined using 7 organisms, 5 media, and 31
      antimicrobial agents. Bacillus stearothermophilus and synthetic assay medium
      (SAM) showed the greatest sensitivity for screening penicillins (penicillin G and
      ampicillin). The combination of Bacillus subtilis and minimum medium (MM) was the
      most sensitive for tetracyclines (oxytetracycline and chlortetracycline), B.
      stearothermophilus and SAM or Micrococcus luteus and Mueller-Hinton agar (MHA)
      for detecting tylosin and erythromycin, B. subtilis and MHA for aminoglycosides
      (streptomycin, kanamycin, gentamicin, and dihydrostreptomycin), B.
      stearothermophilus and SAM for polyethers (salinomycin and lasalocid), and B.
      subtilis and MM or Clostridium perfringens and GAM for polypeptides (thiopeptin,
      enramycin, virginiamycin, and bacitracin). However, gram-negative bacterium
      Escherichia coli ATCC 27166 and MM were better for screening for colistin and
      polymixin-B. For detecting the synthetic drugs tested, the best combination was
      B. subtilis and MM for sulfonamides, E. coli 27166 and MM for quinolones
      (oxolinic acid and nalidixic acid), B. subtilis and MM for furans (furazolidone),
      and the bioluminescent bacterium Photobacterium phosphoreum and luminescence
      assay medium for chloramphenicol and oxolinic acid. The results showed that the
      use of four assay plates, B. stearothermophilus and SAM, B. subtilis and MM, M.
      luteus and MHA, and E. coli 27166 and MM, was superior to the currently available
      techniques for screening for residual antimicrobial agents in edible animal
      tissues.

PMID- 11252481
TI  - Effectiveness of a Lactobacillus sakei starter culture in the reduction of
      biogenic amine accumulation as a function of the raw material quality.
AB  - The effectiveness of an amine-negative starter culture (Lactobacillus sakei
      CTC494) in the reduction of biogenic amine production during the ripening of
      fermented sausages was examined. Four batches were manufactured in parallel:
      spontaneously fermented and starter-mediated sausages were manufactured from two
      lots of raw materials of different hygienic quality. Besides the biogenic amine
      contents, changes in the microbial counts, nitrogenous fractions, pH, and water
      content were measured at several sampling points during the ripening process. In
      sausages manufactured from good quality meat, the starter strain of L. sakei
      reduced and even inhibited biogenic amine accumulation during sausage
      fermentation, the end products showing extremely low biogenic amine contents
      (tyramine levels less than 15 mg/kg of dry matter and putrescine and cadaverine
      levels less than 5 mg/kg of dry matter). Nevertheless, starter-mediated sausages
      made from poorer-quality raw materials showed much higher amine contents (308,
      223, and 36 mg/kg of dry matter of cadaverine, tyramine, and putrescine,
      respectively), which were only slightly lower than those of the spontaneously
      fermented sausages made from the same raw materials. The relatively high
      bacterial numbers of raw materials of poorer-hygienic quality diminished the
      beneficial effect of the starter strain. Therefore, the effectiveness of the
      starter was strongly dependent on the hygienic quality of the raw materials used.

PMID- 11252482
TI  - Biogenic amines in packed table olives and pickles.
AB  - The content of biogenic amines in different commercial preparations of table
      olives and other pickled foods was determined. Concentration of amines in packed
      table olives, capers, caperberries, and cucumbers was less than 60 mg of total
      biogenic amines per kg of fruit, and, therefore, these products represent no risk
      to human health. The highest concentrations of putrescine (50 mg/kg) and
      histamine (38 mg/kg) were found in untreated natural black olives and
      caperberries, respectively. Canned ripe olives were completely free of biogenic
      amines. Putrescine was found in all the samples of green olives and cucumbers but
      at levels lower than 18 mg/kg.

PMID- 11252483
TI  - Antioxidant activity of resveratrol compared with common food additives.
AB  - Resveratrol is a phenolic compound of the stilbene family present in wines and
      various parts of the grape, including the skin. In this study, the antioxidant
      and prooxidant activities of resveratrol were compared with other antioxidants
      (butylated hydroxytoluene [BHT], butylated hydroxyacetone [BHA], phenol, propyl
      gallate [PG], sodium tripolyphosphate [TPP], alpha-tocopherol, and vanillin)
      widely used in foods. The ability of these compounds to inhibit lipid
      peroxidation was as follows: BHA > resveratrol > PG > tripolyphosphate > vanillin
      > phenol > BHT > alpha-tocopherol, the first three inhibiting the peroxidation in
      a concentration-dependent manner. The order of OH* scavenger activity of the
      tested compounds was BHA > TPP > BHT. Resveratrol and vanillin produced between
      10 to 7% and 16 to 10% inhibition of the deoxyribose attack, respectively, but
      they do not scavenge OH*. Neither the resveratrol analyzed nor PG or the rest of
      compounds reacted with H202 and must be considered inefficient in catalyzing any
      subsequent oxidation. The ability to scavenge HOCI was, in decreasing order, PG >
      resveratrol > alpha-tocopherol > phenol. The other compounds did not scavenge
      HOCl.

PMID- 11252484
TI  - Heat resistance of Listeria monocytogenes in vegetables: evaluation of blanching
      processes.
AB  - The heat resistance of a Listeria monocytogenes composite (serotypes 1/2a, 1/2b,
      and 4b) was determined in fresh broccoli florets, sweet green peppers, onions,
      mushrooms, and peas using an end-point procedure in polyester pouches. The heat
      resistance of L. monocytogenes was higher in peas (D(60 degrees C) = 1.0 min) and
      mushrooms (D(60 degrees C) = 0.7 min) than in other vegetables tested (D(60
      degrees C) in onions = 0.2 min) and was highest when cells were subjected to
      starvation before the thermal death time experiments (D(60 degrees C) of starved
      L. monocytogenes in mushrooms = 1.6 min). The results showed that blanching can
      be used as an antilisterial treatment (inactivation of 5 logs of L.
      monocytogenes) when the cold spot of vegetables is treated for at least 10 s at
      75 degrees C or instantaneously (<1 s) at temperatures above 82 degrees C.

PMID- 11252485
TI  - Distribution and prevalence of airborne microorganisms in three commercial
      poultry processing plants.
AB  - Airborne microbial contaminants and indicator organisms were monitored within
      three poultry processing plants (plants A, B, and C). In total, 15 cubic feet
      (c.f.) of air was sampled per location during 15 visits to each plant and
      quantitatively analyzed for total mesophilic and psychrophilic aerobic counts,
      thermophilic campylobacters, Escherichia coli, and Enterobacteriaceae. The
      prevalence of Salmonella spp. in air samples was also evaluated. Significant
      reductions in total aerobic counts were observed between defeathering and
      evisceration areas of the three plants (P < 0.05). Mesophilic plate counts were
      highest in the defeathering areas of all plants compared to equivalent
      psychrophilic plate counts. Enterobacteriaceae counts were highest in the
      defeathering areas of all three plants with counts of log10 1.63, 1.53, and 1.18
      CFU/15 c.f. recovered in plants A, B, and C, respectively. E. coli enumerated
      from air samples in the defeathering areas exhibited a similar trend to those
      obtained for Enterobacteriaceae with log10 1.67, 1.58, and 1.18 CFU for plants A,
      B, and C, respectively. Thermophilic campylobacters were most frequently isolated
      from samples in the defeathering areas followed by the evisceration areas. The
      highest mean counts of the organism were observed in plant A at 21 CFU/15 c.f.
      sample with plants B and C at 9 and 8 CFU/sample, respectively. With the
      exception of low levels of Enterobacteriaceae recovered from samples in the on
      line air chill in plant A, E. coli, Enterobacteriaceae, or Campylobacter spp.
      were not isolated from samples in postevisceration sites in any of the plants
      examined. Salmonella spp. were not recovered from any samples during the course
      of the investigation.

PMID- 11252486
TI  - Effects of ingestion of yogurts containing Bifidobacterium and Lactobacillus
      acidophilus on spleen and Peyer's patch lymphocyte populations in the mouse.
AB  - Certain probiotic lactic acid bacteria have been reported to improve immune
      system function. Here, the effects of ingesting yogurts on lymphocyte populations
      in the spleens and Peyer's patches were determined in mice. Three probiotic
      supplemented yogurts containing Streptococcus thermophilus, Lactobacillus
      bulgaricus, Bifidobacterium, and Lactobacillus acidophilus and one conventional
      yogurt containing only S. thermophilus and L. bulgaricus were prepared from
      commercial starter cultures and used in the study. B6C3F1 female mice were fed
      the four different types of yogurts mixed with an AIN-93G diet in a 50:50 (wt/wt)
      ratio. Nonfat dry milk mixed at a 50:50 (wt/wt) ratio with AIN-93G diet was used
      as the control. After a 14-day feeding period, spleen and Peyer's patches were
      removed and lymphocytes subjected to phenotype analysis by flow cytometry.
      Ingestion of the four yogurts had no effect on percentages of CD8+ (cytotoxic T
      cells), B220+ (B cells), IgA+, or IgM+ cells in spleen or Peyer's patches. The
      percentage of CD4+ (T helper) cells was significantly increased in the spleens
      from one group of mice fed a yogurt containing Bifidobacterium and L.
      acidophilus, and a similar trend was found in the remaining two probiotic
      supplemented yogurts. Effects on CD4+ populations were not observed in spleens of
      mice fed conventional yogurt or in the Peyer's patches of any of the four yogurt
      groups. In total, the results suggested that ingestion of conventional or
      probiotic-supplemented yogurts for 2 weeks had very little effect on lymphocyte
      distribution in the systemic or mucosal immune compartments.

PMID- 11252487
TI  - Resistance to aflatoxin accumulation in kernels of maize inbreds selected for ear
      rot resistance in West and Central Africa.
AB  - Thirty-six inbred lines selected in West and Central Africa for moderate to high
      resistance to maize ear rot under conditions of severe natural infection were
      screened for resistance to aflatoxin contamination using the previously
      established kernel screening assay. Results showed that more than half the
      inbreds accumulated aflatoxins at levels as low as or lower than the resistant
      U.S. lines GT-MAS:gk or MI82. In 10 selected aflatoxin-resistant or aflatoxin
      susceptible inbreds, Aspergillus flavus growth, which was quantified using an A.
      flavus transformant containing a GUS-beta-tubulin reporter gene construct, was,
      in general, positively related to aflatoxin accumulation. However, one aflatoxin
      resistant inbred supported a relatively high level of fungal infection, whereas
      two susceptibles supported relatively low fungal infection. When kernels of the
      10 tested lines were profiled for proteins using sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, significant variations from protein profiles
      of U.S. lines were observed. Confirmation of resistance in promising African
      lines in field trials may significantly broaden the resistant germplasm base
      available for managing aflatoxin contamination through breeding approaches.
      Biochemical resistance markers different from those being identified and
      characterized in U.S. genotypes, such as ones inhibitory to aflatoxin
      biosynthesis rather than to fungal infection, may also be identified in African
      lines. These discoveries could significantly enhance the host resistance strategy
      of pyramiding different traits into agronomically useful maize germplasm to
      control aflatoxin contamination.

PMID- 11252488
TI  - Variation in in vitro alpha-amylase and protease activity is related to the
      virulence of Aspergillus flavus isolates.
AB  - Variation in the ability of Aspergillus flavus isolates to spread between cotton
      boll locules was previously shown to be at least partially related to variation
      in the production of a specific polygalacturonase (pectinase P2C). To determine
      if non-pectolytic hydrolase differences between low- and high-virulence isolates
      exist and, thus, could also potentially contribute to virulence differences, the
      present investigation was undertaken. Two A. flavus isolates, AF12 with low
      virulence and lacking pectinase P2C and AF13 with high virulence and producing
      pectinase P2C, were compared for production of nonpectolytic hydrolases after
      growth in 10% potato dextrose broth. Activity of amylases, cellulases, xylanases,
      and proteases was quantified using the radial diffusion/cup plate technique
      followed by differential staining. Culture filtrates also were subjected to
      native polyacrylamide gel electrophoresis. Both isolates produced amylases,
      proteases, and xylanases, whereas cellulases were not detected for either. AF13
      produced more amylase than AF12, and this difference was supported by amylase
      isoform differences between isolates on native polyacrylamide gel electrophoresis
      gels. AF13 also produced more protease than AF12; however, isoform differences
      between isolates were inconclusive. These variations in other hydrolytic
      activities (besides pectinases) may contribute to virulence differences in cotton
      bolls between AF12 and AF13.

PMID- 11252489
TI  - Polycyclic aromatic hydrocarbons in mussels (Mytilus galloprovincialis) from the
      Ionian Sea, Italy.
AB  - Concentrations of eight polycyclic aromatic hydrocarbons (PAHs) (phenanthrene,
      anthracene, fluoranthene, pyrene, benz[a]anthracene, benzo[a]pyrene,
      dibenz[a,h]anthracene, benzo[ghi]perylene) were determined in mussels (Mytilus
      galloprovincialis) collected between June and September 1995 from 10 locations
      along a sound of sea formed by two inlets (Mar Piccolo) close to the Gulf of
      Taranto (Ionian Sea, Italy). In mussels the concentrations of total PAHs were
      between 14.8 and 645.3 microg/kg wet weight. Among the single identified
      compounds, the predominance of phenanthrene (29.5 microg/kg wet weight) and
      anthracene (64.7 microg/kg wet weight) was evident. Another relevant pollutant
      was pyrene (18.4 microg/kg wet weight) followed by fluoranthene (7.2 microg/kg
      wet weight), whereas the other compounds showed low levels. The mussels that
      showed the highest total concentrations of PAHs were collected from stations
      affected by stronger human activities (industrial fallout, urban wastewaters, and
      contaminants transported via riverine discharge). Our results were similar to
      those found in areas classified as moderately polluted. This observation suggests
      the need for an increased effort in controlling sources of pollution in this area
      recognized as one of the most productive mussel-farming areas in the Italy.

PMID- 11252490
TI  - Heat resistance of Listeria monocytogenes.
AB  - The heat resistance data on Listeria monocytogenes in culture media and foods are
      summarized. Most heat resistance data for foods have been obtained in dairy,
      meat, poultry, and egg products. Limited data have been published on seafood,
      fruits, and vegetables. The methodologies employed have evolved over time; hence
      data from earlier experiments are not directly comparable to more recent studies.
      Many factors influence the heat resistance of L. monocytogenes. Variation exists
      among different strains in their ability to withstand heat treatment. In
      addition, heat resistance is influenced by age of the culture, growth conditions,
      recovery media, and characteristics of foods such as salt content, a(w), acidity,
      and the presence of other inhibitors. Listeriae are more heat resistant than most
      other nonspore-forming foodborne pathogens, and thus, processing recommendations
      based on data from experiments with Salmonella spp. or pathogenic Escherichia
      coli may not be sufficient to eliminate similar numbers of L. monocytogenes. The
      data provided in this review may prove useful for food processors in determining
      appropriate times and temperatures for producing foods free of vegetative
      pathogens.

PMID- 11252491
TI  - PCR primers designed from malic acid dehydrogenase gene and their use for
      detection of Escherichia coli in water and milk samples.
AB  - Escherichia coli has been the appropriate focus for monitoring of potential
      enteric pathogens in water and foods. Although several methods have been used for
      the detection or enumeration of E. coli cells in water and foods, the time and
      accuracy limitations of these methods suggest the need of a rapid and specific
      method. By comparison of the gene sequences coding for malic acid dehydrogenase
      (mdh) of E. coli and non-E. coli strains, two oligonucleotides were designed and
      their possible use as E. coli-specific PCR primers was tested. All of the 110 E.
      coli strains tested, including non-pathogenic and various pathogenic strains,
      generated the expected PCR products with Mw equal to 392 bp. On the other hand,
      only 97 of these 110 E. coli strains were detectable using the BAM gas production
      method. With the exception of Shigella strains, non-E. coli strains, including
      strains of the family of Enterobacteriaceae, did not generate any false positive
      PCR results. When this PCR system was used for the monitoring of E. coli cells
      inoculated into water and milk samples, as low as 10(0) cfu per 100 ml of water
      or per ml of milk sample could be detected if an 8 h preculture step was
      performed prior to the PCR. Including the preculture step, the whole PCR
      detection process may be completed within 12 h.

PMID- 11252492
TI  - Effects of pH, temperature and NaCl concentration on the growth kinetics,
      proteolytic activity and biogenic amine production of Enterococcus faecalis.
AB  - In this work, the combined effects of temperature, pH and NaCl concentration on
      the growth dynamics of Enterococcus faecalis EF37, its proteolytic activity and
      its production of biogenic amines have been studied. The effects of the selected
      variables have been analysed using a Central Composite Design. The production of
      biogenic amines, under the adopted conditions, was found to be mainly dependent
      on the extent of growth of E. faecalis. Its proteolytic activity was not a
      limiting factor for the final amine production, because in the system studied
      (skim milk) an excess of precursors was guaranteed. Quantitatively, the most
      important biogenic amine produced was 2-phenylethylamine but substantial amounts
      of tyramine were detected in all the samples. This work confirms that the main
      biological feature influencing the biogenic amine formation is the extent of
      growth of microorganisms, like E. faecalis, characterised by decarboxylase
      activity. In the traditional and artisanal cheeses produced using raw milk,
      enterococci usually reach levels of 10(7) cells/g. With this perspective, it is
      important that the presence of biogenic amines due to the activities of these
      microorganisms is maintained within safe levels, without affecting the positive
      effects of enterococci on the final organoleptic characteristics of the cheese.

PMID- 11252493
TI  - Assessment of adhesion properties of novel probiotic strains to human intestinal
      mucus.
AB  - Potential new probiotic strains Lactobacillus brevis PELI, L. reuteri ING1, L.
      rhamnosus VTT E-800 and L. rhamnosus LC-705 were assessed for their adhesion
      properties using the human intestinal mucus model. The effect on the adhesion of
      exposure to acid and pepsin and to milk were tested to simulate gastric and food
      processing conditions, and the effect of different growth media on adhesion was
      tested. The properties of the four strains were compared to the well-investigated
      probiotic L. rhamnosus strain GG. Three of the tested strains showed significant
      adhesion properties in the mucus model, while L. brevis PELI had intermediate
      adhesion and L. rhamnosus LC-705 adhered poorly. Pretreatment with different
      milks decreased the adhesion and low pH and pepsin treatment reduced the adhesion
      of all tested strains except L. rhamnosus LC-705. No competitive exclusion of
      pathogenic Salmonella typhimurium or Escherichia coli SfaII was observed. The
      results indicate that major differences exist between tested proposed probiotic
      strains. The growth media and the food matrix significantly affect the adhesive
      ability of the tested strains. This has previously not been taken into account
      when selecting novel probiotic strains.

PMID- 11252494
TI  - Survival of Escherichia coli O157:H7 in frozen foods: impact of the cold shock
      response.
AB  - The survival of Escherichia coli O157:H7 strains in both frozen foods and
      trypticase soy broth (TSB) was investigated following cold shocking at 10 degrees
      C for 1.5 h. Using both trypticase soy agar (TSA) and violet red bile agar (VRBA)
      as recovery media, it was demonstrated that survival levels between cold shocked
      (CS) and non-cold shocked (NS) E. coli in ground beef or pork were not
      significantly different (P < or = 0.05). In contrast, cold shocking E. coli in
      either milk, whole egg or sausage resulted in a significant(P < or = 0.05)
      enhancement in survival. For milk, survival levels of CS E. coli, by 28 days of
      frozen storage, were 1.89 and 1.66 log10 cfu/ml higher on TSA and VRBA,
      respectively, when compared to NS cells. In egg these values were 0.64 and 1.31,
      while in sausage, values of 0.74 and 1.19 were obtained. In TSB (pH 7) survival
      of CS E. coli for some strains was about 3 log10 cfu/ml higher when compared to
      NS cells. Acidification of TSB (pH 5), however, appeared to negate the protective
      effects of the cold shock treatment. In milk, increasing the differential between
      the growth and cold shock temperatures resulted in higher numbers of survivors.
      In this regard the growth-cold shock temperature protocol giving optimum
      protection was 37-10 degrees C. In contrast, growth of E. coli at 20 degrees C
      followed by cold shocking at 10 degrees C did not result in any significant
      freeze protection. In addition, increased protection due to cold shocking was
      correlated with the appearance of a novel protein appearing at pI 4.8 following
      isoelectric focusing analysis, thus demonstrating an alteration of protein
      synthesis.

PMID- 11252495
TI  - Effectiveness of immersion treatments with acids, trisodium phosphate, and herb
      decoctions in reducing populations of Yarrowia lipolytica and naturally occurring
      aerobic microorganisms on raw chicken.
AB  - Yarrowia lipolytica, one of the predominant yeasts in raw poultry, is believed to
      play a role in spoilage. This study was undertaken to investigate treatments to
      control the growth of Y. lipolytica on raw chicken stored at refrigeration
      temperature. Raw chicken wings inoculated with a mixture of five strains of Y.
      lipolytica isolated from raw poultry were dipped in solutions containing 2, 5, or
      8% lactic acid, 2% lactic acid containing 0.2, 0.4, or 0.8% potassium sorbate or
      sodium benzoate, and 4, 8, or 12% trisodium phosphate solution. Populations of
      the yeast and total aerobic microorganisms were determined before and after
      treatment. Immersion of wings in 2% lactic acid (with or without 0.2% potassium
      sorbate or sodium benzoate) or 4% trisodium phosphate caused a significant (alpha
      = 0.05) reduction in numbers of Y. lipolytica and aerobic microorganisms.
      Treatment with 2% lactic acid containing 0.4 or 0.8% preservative did not result
      in additional significant reductions. Treatment of chicken wings with 2% lactic
      acid or 8% trisodium phosphate significantly reduced numbers of Y. lipolytica by
      1.47 and 0.65 log10 cfu/g, respectively, and aerobic microorganisms by 2.60 and
      1.21 log10 cfu/g, respectively, compared to controls. Growth of Y. lipolytica on
      wings stored at 5 degrees C for up to 9 days, however, was not affected by these
      treatments. Significant reductions in the population of Y. lipolytica occurred
      when the yeast was inoculated into 100% basil, marjoram, sage, and thyme
      decoctions, but not in 100% oregano or rosemary decoctions, held at 5 degrees C
      for 24 h. Treatment of chicken wings with 100% sage or thyme decoctions
      significantly reduced populations of Y. lipolytica but did not control its growth
      during storage at 5 degrees C for up to 9 days. The small, temporary decreases in
      numbers of Y. lipolytica and aerobic microorganisms resulting from immersion
      treatment of chicken wings with sage and thyme decoctions render these treatments
      of questionable value as preservation interventions.

PMID- 11252496
TI  - Escherichia coli O157 in cattle and sheep at slaughter, on beef and lamb
      carcasses and in raw beef and lamb products in South Yorkshire, UK.
AB  - A 1 year study of Escherichia coli O157 in cattle and sheep at slaughter, on beef
      and lamb carcasses and in raw beef and lamb products from retail butchers' shops
      was performed in the Sheffield area. Each month, samples of rectal faeces were
      collected immediately after slaughter from 400 cattle and 600 sheep, and 400-430
      samples of raw meat products were purchased from butchers' shops. Meat samples
      were also obtained from 1500 beef and 1500 lamb carcasses. All samples were
      examined for E. coli O157 by enrichment culture, immunomagnetic separation and
      culture of magnetic particles onto cefixime tellurite sorbitol MacConkey agar.
      Raw meat products were also examined for numbers of generic E. coli by a standard
      membrane culture method. E. coli O157 was isolated from 620 (12.9%) of 4800
      cattle, 100 (7.4%) of 7200 sheep, 21 (1.4%) of 1500 beef carcasses, 10 (0.7%) of
      1500 lamb carcasses and from 22 (0.44%) of 4983 raw meat products. E. coli O157
      was isolated more frequently from lamb products (0.8%) than from beef products
      (0.4%). Numbers of generic E. coli in meat products reached seasonal peaks in
      July and August with counts of > 10(4)/g occurring more frequently in lamb
      products (50.8 and 42.4%, respectively) than in beef products (19.3 and 23.8%,
      respectively). The majority of E. coli O157 strains, from animals, carcasses and
      meat samples, were isolated during the summer. Most were verocytotoxigenic as
      determined by Vero cell assay and DNA hybridisation, eaeA gene positive and
      contained a 92 kb plasmid. The isolates were compared with 66 isolates from human
      cases over the same period. A combination of phage type, toxin genotype and
      plasmid analysis allowed subdivision of all the E. coli O157 isolates into 96
      subtypes. Of these subtypes, 53 (55%) were isolated only from bovine faecal
      samples. However, 61 (92%) of the 66 isolates from humans belonged to 13 subtypes
      which were also found in the animal population.

PMID- 11252497
TI  - Pre-inoculation enrichment procedure enhances the performance of
      bacteriocinogenic Lactococcus lactis meat starter culture.
AB  - Sodium nitrite and sodium chloride may inhibit growth and bacteriocinogenesis of
      protective starter cultures. To reduce sensitivity of a lacticin 3147-producing
      starter culture to nitrite, prior to production of salami, Lactococcus lactis DPC
      4275 was placed in a number of pre-inoculation treatments, containing (a) 1%
      glucose, (b) 2.5 ppm manganese (Mn), (c) 250 ppm magnesium (Mg), (d) 2.5 ppm
      manganese + 250 ppm magnesium (Mn + Mg), and held at ambient temperature for 30
      min and 4 degrees C for 2 h. The growth, pH reduction, and bacteriocin production
      was monitored in beaker sausage over a period of 10 days at 28 degrees C,
      corresponding to typical salami production time, and compared to untreated
      starter culture. The effect of 1% tryptone and inoculum level on growth and
      bacteriocin production was also determined. Challenge tests were performed using
      Listeria innocua DPC 1770 and Staphylococcus aureus MMPR3 as target strains. All
      treatments gave a significantly higher (P < 0.05) initial starter level than the
      untreated starter. Beaker sausage inoculated with either low (10(7)) or high
      (10(9)) levels of starter culture, treated with Mn + Mg reached significantly (P
      < 0.05) higher levels by day 10 than other treatments. Trends indicate that Mn +
      Mg also gave best pH reduction in sausage containing the low-level starter
      culture, sausage and significantly lower (P < 0.05) values for sausage produced
      with higher inoculum. Bacteriocin production was also higher in starter culture
      treated with Mn, or glucose. Pre-treatment with Mg gave a 2-fold increase in
      bacteriocin, the addition of Mn augmenting this increase further. The
      incorporation of tryptone gave no additional effect. In beaker sausage, both L.
      innocua and S. aureus populations showed significant reductions (P < 0.05) in the
      presence of the bacteriocinogenic strain compared to a non-bacteriocinogenic
      control strain.

PMID- 11252498
TI  - Consumers and foodborne diseases: knowledge, attitudes and reported behavior in
      one region of Italy.
AB  - A survey was conducted to investigate knowledge, attitudes and related behavior
      on foodborne diseases and food-handling practices among consumers in one region
      of Italy. A self-administered questionnaire was offered to a random sample of
      mothers of children attending public schools. Of the 394 responding mothers, 36%
      knew about all the six foodborne pathogens investigated but only 11.1% correctly
      indicated six related different food vehicles; education level was a predictor of
      this knowledge. A positive attitude towards foodborne disease control,
      significantly higher in older and more educated women, was reported by the great
      majority, who agreed that improper storage of food represents a health hazard
      (95.7%), that washing hands before handling unwrapped raw or cooked food reduces
      the risk of food poisoning (93.2%), and that the awareness of the temperature of
      the refrigerator is crucial in reducing risk of food poisoning (90.1%). Only
      53.9% reported washing hands before and after touching raw or unwrapped food and
      50.4% reported using soap to wash hands. A total of 75.6% clean kitchen benches
      after every use and 81.1% use hot water and soap for this purpose. Only 25.6%
      thaw food in the refrigerator and 49.9% put leftovers in the refrigerator soon
      after meals. Washing hands before and after touching unwrapped food was
      significantly higher in women living in larger families and who had been informed
      by physicians about foodborne diseases. Educational programs and the counseling
      efforts of physicians, particularly focused to less educated subjects, are
      greatly needed.

PMID- 11252499
TI  - Cresol red thallium acetate sucrose inulin (CTSI) agar for the selective recovery
      of Carnobacterium spp.
AB  - Carnobacterium spp. are commonly isolated from a variety of foods, especially
      from meats stored under anaerobic atmospheres at refrigeration temperatures, but
      the role of these organisms in the spoilage of meat and meat products is yet to
      be determined. Cresol Red Thallium Acetate Sucrose (CTAS) agar was developed as a
      selective medium for enumeration of carnobacteria, however problems such as poor
      recovery of Carnobacterium spp. and interference by other microorganisms have
      precluded its general use. The aim of this study was to improve CTAS agar by
      broadening its spectrum of selective recovery for carnobacteria while restricting
      the ability of interfering species to grow. Ten Carnobacterium spp. (five ATCC
      cultures and five isolates from fresh pork) and 20 other genera were used in
      testing the agar. A wider range of Carnobacterium spp. recovery was obtained by
      modifying concentrations of sucrose, manganese sulphate and thallium acetate.
      Additions of inulin and thiamine hydrochloride also improved growth response. The
      additions of vancomycin and Chrisin (nisin) eliminated interference from other
      microorganisms. A two-temperature incubation procedure was included to improve
      the characteristic growth of Carnobacterium spp. on the modified medium,
      identified as Cresol Red Thallium Sucrose Inulin (CTSI) agar. Lactic acid
      bacteria and Enterobacteriaceae were unable to grow on CTSI incubated
      aerobically. Growth of Carnobacterium spp. on CTSI yielded pink colonies, except
      for Cb. mobile, which formed gray colonies. In some instances, a red precipitate
      formed in the center of the colony. Yellowing and clearing of the growth medium
      was also frequently observed. Recovery of carnobacteria using CTSI was identical
      to that obtained with All Purpose Tween (APT) agar.

PMID- 11252501
TI  - Determination of peroxy radical-scavenging of lactic acid bacteria.
AB  - Responses of lactic acid bacteria (LAB) to peroxy radicals generated via thermal
      (40 degrees C) decomposition of the diazocompound 2,2,-azo-bis (2-amidinopropane)
      dihydrochloride (ABAP), were studied. In general, LAB displayed survival curves
      with shoulders and tails indicative of 'multihit' killing by exposure to peroxy
      radicals. One strain, Lactococcus lactis subsp. lactis DIP15, producing a slope
      of 0.0105 in the kinetic analysis when exposed to 4 mM ABAP, exhibited a
      measurable antioxidant capacity. The other LAB failed to show any significant
      antioxidant capacity. The antioxidant capacity of strain DIP15 remained constant
      after cells have been heat-treated, suggesting that compounds bearing free
      radical scavenging capacity are rather stable.

PMID- 11252502
TI  - Occurrence of Salmonella spp. in consumption eggs in Poland.
AB  - The purpose of this study was to determine the prevalence of Salmonellae on egg
      shells in markets in Olsztyn, Poland. An investigation carried out by the
      Sanitary and Epidemiological Station into cases of food poisoning caused in
      Poland by Salmonella spp. in recent years showed that the largest number of
      outbreaks is connected with consuming foods containing hens eggs which had not
      undergone heat treatment, such as mayonnaise, creams, ice-cream and other
      products. The world egg production amounts to 400 billion, in Poland it reaches
      the level of around 8 billion per year. A total of 1200 eggs were purchased in 40
      local markets in Olsztyn were examined for the presence of Salmonella between
      June 1997 and December 1998. Salmonella was not found on the shell or inside the
      eggs. From this study it would appear that the incidence of Salmonellae on eggs
      from Olsztyn shops is very low.

PMID- 11252500
TI  - Effect of aqueous extracts of some plants of Lamiaceae family on the growth of
      Yarrowia lipolytica.
AB  - Aqueous extracts of some plants belonging to the Lamiaceae family (Sideritis
      montana, Origanum dictamnus, Mentha piperita, Rosmarinus officinallis and
      Origanum marjorana) caused an important increase of the lag time of Yarrowia
      lipolytica. Especially, Origanum dictamnus and Rosmarinus officinallis extracts
      enhanced the lag time considerably and influenced negatively the specific growth
      rate of this yeast. In culture media having low C/N ratio, all plant extracts
      caused an increase of the biomass produced in relation to glucose and nitrogen
      consumed, while, in high C/N ratio media the effect of the extracts on biomass
      production was negative. In the presence of aqueous plant extracts, in low C/N
      ratio culture media, the ratio sigma unsaturated/sigma saturated fatty acids in
      the cellular lipids increased, whereas in high C/N ratio media it decreased.

PMID- 11252503
TI  - Detection and preliminary characterization of a bacteriocin (plantaricin 35d)
      produced by a Lactobacillus plantarum strain.
AB  - Lactic acid bacteria (134) from Italian sausages were tested for the production
      of antimicrobial substances (bacteriocins). Six percent of these showed
      antibacterial activity against one or several closely related microorganisms used
      as indicators. Lactobacillus plantarum 35d in particular produced a bacteriocin
      of high activity (320 AU ml(-1)) and a wide range of antimicrobial activity
      including S. aureus, L. monocytogenes, and A. hydrophila. The bacteriocin
      withstood heating at 80 degrees C for 120 min and storage at 4 degrees C for 6
      months. The mode of action was identified as bactericidal. The apparent molecular
      weight of the bacteriocin extracted with n-butanol was estimated to be 4.5 kDa.

PMID- 11252504
TI  - Factors affecting capsule size and production by lactic acid bacteria used as
      dairy starter cultures.
AB  - The effects of sugar substrates on capsule size and production by some capsule
      forming nonropy and ropy dairy starter cultures were studied. Test sugars
      (glucose, lactose, galactose, or sucrose) were used as a sole carbohydrate source
      and the presence of a capsule and its size were determined by using confocal
      scanning laser microscopy. Nonropy strains produced maximum capsule size when
      grown in milk. Strains that did not produce capsules in milk did not produce them
      in any other growth medium. Specific sugars required for capsule production were
      strain-dependent. Increasing lactose content of Elliker broth from 0.5 to 5% or
      adding whey protein or casein digest produced larger capsules. Whey protein
      concentrate stimulated production of larger capsules than did casamino acids or
      casitone. Some Streptococcus thermophilus strains produced capsules when grown on
      galactose only. Nonropy strains of Lactobacillus delbrueckii subsp. bulgaricus
      produced capsules on lactose, but not on glucose. A ropy strain of Lactobacillus
      delbrueckii subsp. bulgaricus produced a constant capsule size regardless of the
      growth medium. The ability of some strains of Streptococcus thermophilus to use
      galactose in capsule production could reduce browning of mozzarella cheese during
      baking by removing a source of reducing sugar. Media that do not support capsule
      production may improve cell harvesting.

PMID- 11252505
TI  - Dry sausage fermented by Lactobacillus rhamnosus strains.
AB  - The ability of three probiotic Lactobacillus rhamnosus strains GG, E-97800 and LC
      705 and one commercial Pediococcus pentosaceus starter strain (control) to
      produce dry sausage was studied. During the fermentation process the numbers of
      inoculated lactic acid bacteria increased from approx. 7 log10 to 8-9 log10 cfu/g
      and the pH values decreased from 5.6 to 4.9-5.0. The sensory test indicated that
      the dry sausages fermented by L. rhamnosus LC-705 were inferior to the control
      sausages. The presence of inoculated experimental strains as predominant
      organisms in the dry sausages was recognised on the basis of their genetic
      fingerprints by ribotyping. The concentrations of biogenic amines remained low
      during the ripening process. These results indicated that the studied
      Lactobacillus rhamnosus strains, especially strains GG and E-97800, are suitable
      for use as probiotic starter cultures in fermenting dry sausage.

PMID- 11252507
TI  - Distribution of aflatoxin M1 in cheese obtained from milk artificially
      contaminated.
AB  - Small-scale manufacture of cheese using artificially AFM1 contaminated milk as
      raw material to study the distribution of such toxin both in whey and in cheese,
      was carried out. Whole milk with undetectable levels of AFM1 was used. The toxin
      was added in concentration that varied from 1.7 to 2.0 microg/l of milk. After
      the home-made production of cheese, the concentration of AFM1 was determined both
      in whey and in cheese, using the enzymatic immunoassay technique. The greatest
      proportion, 60%, was detected in whey while 40% AFM1 remained in cheese.

PMID- 11252506
TI  - Lactic acid bacterial diversity in the traditional mexican fermented dough pozol
      as determined by 16S rDNA sequence analysis.
AB  - The lactic acid bacteria diversity of pozol, a Mexican fermented maize dough, was
      studied using a total DNA extraction and purification procedure and PCR
      amplification of 16S rDNA for gram-positive and related bacterial groups. Thirty
      six clones were obtained and sequenced to 650 nucleotides. These partial
      sequences were identified by submission to the non-redundant nucleotide database
      of NCBI. The identified sequences were aligned with reference sequences of the
      closest related organisms. This analysis indicated that only 14 sequences were
      unique clones and these were identified as Lactococcus lactis, Streptococcus
      suis, Lactobacillus plantarum, Lact. casei, Lact. alimentarium, and Lact.
      delbruekii and Clostridium sp. Two non-ribosomal sequences were also detected.
      Unlike other environments analyzed with this molecular approach where many
      unidentified microorganisms are found, the identity of most sequences could be
      established as lactic acid bacteria, indicating that this is the main group among
      the gram-positive bacteria in pozol. Use of this molecular method permitted
      detection of lactic acid bacteria different from those previously isolated and
      identified by culture techniques

PMID- 11252508
TI  - Survival of Listeria monocytogenes during manufacture, ripening and storage of
      soft lactic cheese made from raw goat milk.
AB  - Soft lactic cheeses were manufactured with raw goat milk inoculated with Listeria
      monocytogenes. The physico-chemical and microbiological characteristics of curds
      and cheeses were determined after each processing step as well as during ripening
      and refrigerated storage. The fate of Listeria monocytogenes was evaluated by
      enumeration on PALCAM agar and by a qualitative detection after a double
      selective enrichment procedure. The results showed that the physico-chemical and
      microbiological characteristics of lactic cheeses caused a decrease of Listeria
      monocytogenes counts. However, this decrease did not lead to the complete
      disappearance of the pathogen and Listeria monocytogenes was able to survive in
      soft lactic cheeses made with raw goat milk.

PMID- 11252509
TI  - Analytical chromatography for recovery of small amounts of staphylococcal
      enterotoxins from food.
AB  - Sample preparation is an important element in the detection of toxins in food
      samples. In this work, a simple analytical sample preparation method for recovery
      of small amount of staphylococcal enterotoxin B (SEB) and staphylococcal
      enterotoxin A (SEA) in food samples was developed. Cation exchanger
      carboxymethylcellulose (CM) was used for small-scale batch chromatography
      isolation of SEB from infant formula and from mushrooms spiked with SEB. The
      resulting materials were analyzed for SEB by Western immunoblotting. Nearly all
      of the extraneous substances in the sample were removed by this procedure with no
      significant loss of the toxin. Using this method, even small amounts of SE (0.75
      ng/g) can be recovered and immunologically analyzed by Western blotting or by
      ELISA with a very low background. Because this method is effective, rapid, simple
      and inexpensive, it has the potential to be a general method for the preparation
      of samples used for analysis of SEs.

PMID- 11252510
TI  - Prevalence of glycopeptide and aminoglycoside resistance in Enterococcus and
      Listeria spp. in low microbial load diets of neutropenic hospital patients.
AB  - Low microbial load diets for patients with haematological malignancy were
      examined for enterococci and listeria using pre-enrichment, enrichment and
      selective plating. Enterococci were highly prevalent and their ecology diverse;
      100/211 samples yielded 132 isolates made up of 67 strains distinguishable by
      PFGE. Listeria monocytogenes was not found. Screening of enterococci for
      antibiotic resistance showed low level vancomycin resistance (6-12 microg/ml) in
      six isolates of E. gallinarum and high level streptomycin resistance (> or = 1000
      microg/ml) in eight isolates from various foods. No strains showing high level
      glycopeptide or gentamicin resistance were found. The high prevalence of
      enterococci in food processed for safety indicates a possible route for the
      acquisition of antibiotic-resistant strains by vulnerable hospital patients.

PMID- 11252511
TI  - Use of PFGE typing for tracing contamination with Listeria monocytogenes in three
      cold-smoked salmon processing plants.
AB  - The sites of Listeria monocytogenes contamination in three cold-smoked salmon
      (Salmo salar) processing plants were detected by sampling salmon and the plant's
      environment and equipment at different production stages. Of the 141 samples
      collected from three processing plants, 59 (42%) were contaminated with L.
      monocytogenes. The rates of contamination varied as to the plant and the sample
      source. L. monocytogenes isolates from 17 various contaminated seafood products
      (fresh, frozen and smoked fishes, cooked mussels) were also studied. A total of
      155 isolates from the three plants and the various seafoods were characterized by
      genomic macrorestriction using ApaI and SmaI with pulsed-field gel
      electrophoresis (PFGE) and 82 isolates were serotyped. Macrorestriction yielded
      20 pulsotypes and serotyping yielded four serovars: 1/2a, 1/2b, 1/2c, 4b (or e),
      with 77 (93%) belonging to serovar 1/2a. One clone of L. monocvtogenes
      predominated and persisted in plant I and was the only pulsotype detected in the
      final product although it was not isolated from raw salmon. No L. monocytogenes
      was detected in the smoked skinned salmon processed in plant II, even though 87%
      of the raw salmon was contaminated. All the smoked salmon samples collected in
      plant III were contaminated with a unique clone of L. monocytogenes, which may
      have occurred during slicing. In the three plants, the contamination of final
      products did not seem to originate from the L. monocytogenes present on raw
      salmon, but from the processing environment.

PMID- 11252512
TI  - Detection of genes encoding for enterotoxins and determination of the production
      of enterotoxins by HBL blood plates and immunoassays of psychrotrophic strains of
      Bacillus cereus isolated from pasteurised milk.
AB  - The presence of genes for the production of the three components of the HBL
      enterotoxin complex and enterotoxin-T in Bacillus cereus was evaluated by PCR
      tests for strains isolated from milk. In addition enterotoxin production of B.
      cereus was evaluated by means of the HBL blood agar plate and two commercially
      available toxin tests. All three genes for the HBL enterotoxin complex were
      detected in 55% of the 86 strains tested, the enterotoxin-T gene was detected in
      62% of the strains. A few strains showed a weak reaction in the PCR tests for the
      L1 or L2 components of the HBL enterotoxin complex. Many strains that were found
      to contain the genes for the HBL complex gave negative or doubtful results in the
      HBL blood agar plate test. All strains that contain the L2 part of the HBL
      complex showed a titer of at least 8 in the Oxoid RPLA test. Two strains that did
      not contain the L2 part of the HBL enterotoxin complex gave high titers (= 64) in
      the RPLA test.

PMID- 11252513
TI  - Physiological function of exopolysaccharides produced by Lactococcus lactis.
AB  - The physiological function of EPS produced by Lactococcus lactis was studied by
      comparing the tolerance of the non-EPS producing strain L. lactis ssp. cremoris
      MG1614 and an EPS producing isogenic variant of this strain to several anti
      microbial factors. There was no difference in the sensitivity of the strains to
      increased temperatures, freezing or freeze-drying and the antibiotics, penicillin
      and vancomycin. A model system showed that EPS production did not affect the
      survival of L. lactis during passage through the gastrointestinal tract although
      the EPS itself was not degraded during this passage. The presence of cell
      associated EPS and EPS in suspension resulted in an increased tolerance to copper
      and nisin. Furthermore, cell associated EPS also protected the bacteria against
      bacteriophages and the cell wall degrading enzyme lysozyme. However, it has not
      been possible, so far, to increase EPS production using the presence of copper,
      nisin, lysozyme or bacteriophages as inducing factors.

PMID- 11252514
TI  - Influence of agar content on the growth parameters of Bacillus cereus.
AB  - Factors governing Bacillus cereus colony growth on agar media as modified by the
      agar content (1-7%, w/v) were studied. Agar had a significant effect on the
      radial growth rate which diminished as the agar content increased. Cell density
      in colonies (colony density) was found to decrease during the incubation time,
      with lower values occurring in the presence of 1% agar. Size and DNA content of
      the cells grown on 1 and 7% agar were similar. An increasing proportion of cell
      population growing on 7% agar produced spores during the 24-h incubation period.
      It was shown that 'water condition' on the agar surface could be associated with
      colony density, with 7% agar media presenting the thinnest nominal thickness of
      the liquid film. On the other hand, the partial drying phenomena of the agar
      media which occur during preparation and incubation, could not account for the
      observed differences in colony growth.

PMID- 11252515
TI  - VanA-type vancomycin-resistant enterococci (VRE) remain prevalent in poultry
      carcasses 3 years after avoparcin was banned.
AB  - Avoparcin was used as a growth promoting feed additive in Norwegian broiler and
      turkey production from 1986 until it was banned in 1995, when an association
      between vancomycin-resistant enterococci (VRE) and avoparcin use became apparent.
      A recent study regarding faecal samples documented a continuing high prevalence
      of VRE among Norwegian poultry 3 years after avoparcin was banned. In the present
      study, carcasses of broilers and turkeys from farms where avoparcin had
      previously been in use and carcasses of layer chickens from farms where avoparcin
      had never been used were examined for the presence of VRE. One carcass from each
      of 150 different farms was included. By a direct plating method, VRE were
      isolated from 30 of 100 samples of broilers and turkeys, but not from any samples
      of layer chickens. When an enrichment step was included, VRE were isolated from a
      total of 81 of the 100 samples of broilers and turkeys and from nine of the 50
      samples of layer chickens. All VRE isolated were highly resistant to vancomycin
      (MIC > or = 256 microg/ml) and possessed the vanA gene. These results correspond
      to the prevalence of VRE recently documented in faecal samples from Norwegian
      poultry. The present study reveals a high prevalence of VRE in broiler and turkey
      carcasses. Consequently, consumers are exposed to VRE when handling raw poultry
      meat, although the public health significance of such exposure is unclear.

PMID- 11252516
TI  - Phenotypic and molecular identification and clustering of lactic acid bacteria
      and yeasts from wheat (species Triticum durum and Triticum aestivum) sourdoughs
      of Southern Italy.
AB  - The microflora of 25 wheat sourdoughs from the Apulia region, Southern Italy, was
      characterized. The sourdoughs were mainly produced from Triticum durum wheat. The
      number of lactic acid bacteria and yeasts ranged from ca. log 7.5 to log 9.3
      colony forming units (cfu)/g and from log 5.5 to log 8.4 cfu/g, respectively.
      About 38% of the 317 isolates of lactic acid bacteria were identified by
      conventional physiological and biochemical tests. Phenotypic identification was
      confirmed by 16S rDNA and 16S/23S rRNA spacer region PCR. Overall, 30% of the
      isolates were identified as Lactobacillus sanfranciscensis, 20% as Lb.
      alimentarius, 14% as Lb. brevis, 12% as Leuconostoc citreum, 7% as Lb. plantarum,
      6% as Lactococcus lactis subsp. lactis, 4% as Lb. fermentum and Lb. acidophilus,
      2% as Weissella confusa and 1% as Lb. delbrueckii subsp. delbrueckii. Some of
      these species have not been previously isolated from sourdoughs. Since bakers
      yeast is widely used in sourdough production, Saccharomyces cerevisiae was
      largely found. The phenotypical relationships within the main lactic acid
      bacteria identified were established by using cluster analysis. A microbial map
      of the 25 sourdoughs was plotted showing characteristic associations among lactic
      acid bacteria and differences in the lactic acid bacteria species which were
      mainly due to the species of wheat flour, use of bakers yeast and type of bread.

PMID- 11252517
TI  - From pharmacological profiles to clinical outcomes.
AB  - The reformulated dopamine hypothesis of schizophrenia postulates that over
      activity of dopaminergic neurones in limbic areas of the brain is responsible for
      the positive symptoms of the illness. At the same time, dopaminergic under
      activity in the frontal cortex is thought to underlie the negative symptoms and
      cognitive impairment. In addition, it has emerged that classical dopaminergic D2
      receptors comprise a family of several different subtypes of which D2 is widely
      distributed, whereas D3 and D4 are concentrated in limbic and cortical areas.
      Amisulpride selectively blocks D2 and D3 receptors but with preference for the
      latter. Amisulpride also has preferential activity at presynaptic rather than
      postsynaptic receptors. It was predicted therefore that amisulpride would
      alleviate both the under-activity in the frontal cortex and the over-activity in
      the limbic system. Amisulpride is also virtually free of activity at receptors
      for other neurotransmitters. This unique pharmacology is consistent with the
      therapeutic profile of amisulpride, which has been clearly demonstrated to
      control both the positive and negative symptoms of schizophrenia with equal
      efficacy as well as being well tolerated.

PMID- 11252518
TI  - Long-term phase of schizophrenia: impact of atypical agents.
AB  - Typical antipsychotic agents are poorly suited to the long-term treatment of
      schizophrenia, particularly since the introduction of atypical compounds has
      increased the expectations of both physicians and patients. Well-being and
      quality of life--now important considerations--have shown significant
      improvements in patients treated with atypical agents such as amisulpride rather
      than typical agents such as haloperidol. This is associated with alleviation of
      negative symptoms and cognitive deficits, benefits which are not seen with
      traditional agents and which increase the likelihood of successful
      rehabilitation.

PMID- 11252519
TI  - Switching approach in the management of schizophrenia patients.
AB  - Atypical neuroleptics combine efficacy with good tolerability. As a result,
      prognosis and quality of life may improve when patients receiving treatment with
      traditional agents are switched to an atypical compound. Major indications for
      switching are lack of or incomplete response to classical neuroleptic treatment,
      and/or the occurrence of extrapyramidal symptoms. The previous treatment should
      be discontinued, preferably progressively, and the new one started, overlapping
      the previous treatment. Caution is advised in patients who have suffered a recent
      relapse, a severe psychotic episode or who are being treated as outpatients.
      Anticholinergic medication, if needed, should be continued for 2-4 weeks after
      the switch has been made. The physician should be aware of the potential drug
      interactions leading to increased sedation or hypotension. Patient education is
      vital when switching medications. Treatment should be individualized. Patients
      who have gained weight on previous therapy, or who have negative symptoms of
      schizophrenia and depressive symptoms, are particularly likely to benefit from
      amisulpride. Furthermore, the highly selective affinity of amisulpride for
      dopaminergic receptors with its lack of interference with other neurotransmitter
      systems facilitates the change in treatment.

PMID- 11252520
TI  - Is amisulpride an 'atypical' atypical antipsychotic agent?
AB  - Amisulpride is a novel antipsychotic with a pharmacological and clinical profile
      that differs from that of other atypical agents. Amisulpride is highly selective
      for dopamine D2/D3 receptor subtypes located in the limbic region, which is
      highly predictive of potent antipsychotic activity with a low potential to cause
      extrapyramidal symptoms (EPS). At the same time, its selective activity at
      presynaptic D2/D3 receptors is responsible for enhancing dopamine transmission,
      which predicts efficacy in the treatment of the negative symptoms of
      schizophrenia. Amisulpride thus has a unique profile: efficacy in controlling the
      symptoms of schizophrenia, whether predominantly positive or negative, combined
      with a low incidence of EPS. This profile is seen during both acute and chronic
      treatment. Amisulpride is therefore indeed an 'atypical atypical'--a flexible
      antipsychotic the use of which can be tailored to the changing needs of the
      patient. It is thus a suitable first-line choice for the treatment of
      schizophrenia.

PMID- 11252521
TI  - Acute phase of schizophrenia: impact of atypical antipsychotics.
AB  - The acute phase of schizophrenia is characterized by the presence of positive,
      negative and affective symptoms. After recovery, patients still may suffer
      distressing residual symptoms; they also carry a high risk of relapse which may
      be associated with further deterioration in their condition. Prompt, early and
      continued treatment with an effective, well-tolerated antipsychotic agent, is
      therefore crucial. Typical antipsychotics are poorly tolerated, leading to lack
      of compliance and relapse. They also lack efficacy in controlling negative and
      affective symptoms. Atypical compounds such as amisulpride or risperidone are
      better tolerated. In addition, when compared with either haloperidol or
      risperidone, amisulpride has been shown to be at least as effective in
      controlling positive symptoms and significantly superior in alleviating negative
      symptoms. The onset of action of amisulpride appears more rapid than that of
      haloperidol. Amisulpride therefore fulfils all the requirements of a first-line
      agent for the treatment of the acute phase of schizophrenia.

PMID- 11252522
TI  - Progress defined--short-term efficacy, long-term effectiveness.
AB  - The management of schizophrenia continues to represent an enormous challenge,
      despite improvements in both drug therapy and family and community interventions.
      Treatment expectations have shifted from the primary goal of controlling positive
      symptoms to a more comprehensive approach, with the aim of providing relief in
      all symptom domains, preventing relapses, improving compliance and ultimately
      improving functional outcomes in patients with schizophrenia. The advent of a new
      generation of 'atypical' antipsychotics should aid clinicians in meeting these
      goals. These agents combine high antipsychotic efficacy with improved
      tolerability profiles, mainly through a low liability for extrapyramidal
      symptoms. There is enough evidence from randomized, double-blind trials to
      demonstrate efficacy of atypical antipsychotics in improving global
      psychopathology, positive, negative, affective and cognitive symptoms, as well as
      preventing relapse during long-term use. These drugs may, therefore, provide
      clinicians with a new and important addition for first-line management of
      schizophrenia.

PMID- 11252523
TI  - Barriers to progress--the impact of tolerability problems.
AB  - Side-effects of antipsychotic treatment are important factors in patients'
      compliance with treatment regimens. Of particular relevance to compliance are
      extrapyramidal symptoms (EPS), sedation, weight gain and sexual dysfunction. The
      new, atypical antipsychotics offer several tolerability benefits over
      conventional neuroleptics, particularly with respect to EPS. However, differences
      in their receptor binding characteristics result in different side-effect
      profiles. All novel antipsychotics have a high 5-HT2 to D2 receptor binding
      ratio, which is postulated to be important for a low liability for EPS.
      Ziprasidone, a new antipsychotic in the late stages of clinical development, has
      a low affinity for some receptor types, activation of which has been linked with
      adverse events such as sedation, postural hypotension, weight gain and cognitive
      impairment; for example, ziprasidone has minimal activity at muscarinic (M1),
      histaminergic (H1) and alpha1-adrenergic receptors. In short- and long-term
      clinical trials, ziprasidone had a low liability for side-effects typically
      associated with poor compliance, such as EPS, weight gain and sexual dysfunction.
      The tolerability profiles of the new antipsychotics represent a major improvement
      over the older neuroleptics. The more favourable the benefit/risk ratios of these
      new drugs throughout all phases of treatment, the greater the likelihood that
      patients will have better outcomes.

PMID- 11252524
TI  - Real progress--the patient's perspective.
AB  - Experience from a UK national telephone helpline SANELINE (run by the mental
      health charity SANE), showed that availability and access to better medications
      and services are among the most important issues for patients with mental
      illness. SANELINE, therefore, conducted a survey of patients' satisfaction with
      antipsychotic medication between July 1998 and February 1999. A total of 202
      completed questionnaires were available for analysis. A majority of patients
      (56%) were treated with conventional neuroleptics, 20% with new 'atypical'
      antipsychotics and 11% were on a combination of conventional and novel
      antipsychotics. Virtually all respondents (99%) reported suffering from at least
      one side-effect, of which 31% were perceived as 'severe' or 'very severe'. The
      most common side-effects reported were depression/low mood (90%), sedation (88%),
      difficulty in thinking/concentrating (78%), insomnia (68%), dry mouth (65%),
      muscle/joint stiffness (45%), sexual dysfunction (43%) and weight gain (39%).
      Notably, 73% of those who had experienced weight gain reported it to be 'quite or
      extremely distressing'. Depression was rated as 'quite or extremely distressing'
      by 67% of sufferers and insomnia was similarly rated by 66% of patients. Despite
      the methodological limitations of the survey, the results suggest there is a high
      level of patient dissatisfaction and distress related to the currently available
      medications, which may have unfavourable effects on compliance and treatment
      outcome.

PMID- 11252525
TI  - Sustaining short-term gains for future progress.
AB  - Management of patients with acute psychosis represents a considerable challenge
      for many reasons. As acute psychosis is considered to be a psychiatric emergency
      that requires immediate and effective intervention, pharmacotherapy with
      antipsychotic drugs is the mainstay of treatment. The key treatment goals are to
      calm the agitated, assaultive, violent or disruptive patient, to minimize the
      danger to self and others and to achieve a smooth transition from intramuscular
      to oral maintenance treatment with mimimal side-effects. In most circumstances
      intramuscular formulations of antipsychotic drugs are the optimal treatment
      choice. However, only the conventional antipsychotics are currently available as
      intramuscular formulations and unfavourable tolerability profiles reduce the
      benefit/risk ratio and may make future transition to oral treatment problematic.
      An intramuscular formulation of an atypical antipsychotic medication would have
      significant advantages, not only during the acute psychotic phase but also during
      transition to oral maintenance treatment by enabling an effective and well
      tolerated changeover from intramuscular to oral drug treatment.

PMID- 11252526
TI  - 29th Annual International Neuropsychological Society Conference. February 14-17,
      2001. Chicago, Illinois, USA. Abstracts.

PMID- 11252527
TI  - Regulation of myosin expression in developing and regenerating extrafusal and
      intrafusal muscle fibers with special emphasis on the role of thyroid hormones.
AB  - Expression of the muscle phenotype is the result of interaction between intrinsic
      and extrinsic factors, the latter including innervation, mechanical influences
      and hormonal signals. This minireview summarizes some of the current knowledge
      regarding the regulation of myosin heavy chain (MHC) isoform transitions during
      muscle development and regeneration. It describes the role of genetic factors,
      neural and mechanical influences and it focuses on the contribution of thyroid
      hormones to the differentiation of muscle fiber phenotypes as shown by the
      regulation of the expression of MHC isoforms and development of myofibrillar
      ATPase activity. Finally, it shortly summarizes results regarding the
      differentiation of MHC isoforms in regenerated muscle fibers of the graft after
      heterochronous isotransplantation in rats with different thyroid status.

PMID- 11252528
TI  - Evaluating the outcome of percutaneous transluminal angioplasty in renal graft
      artery stenosis using the areas under the time curve of glomerular filtration
      rate and blood pressure.
AB  - The benefit of percutaneous transluminal angioplasty (PTA) of transplant renal
      artery stenosis for ischemic nephropathy may be adversely affected by rejection
      or other complications. As a result, assessment of the effect of PTA on renal
      function or blood pressure is often difficult. In this paper, we evaluated the
      effect of PTA using the method of integrated glomerular filtration rate (GFR)
      based upon the area under the curve over a follow-up period (AUC0-1), to express
      the level of GFR in a simple manner despite its significant fluctuations. A
      similar procedure was used to evaluate mean arterial pressure (MAP). The method
      was employed to assess the outcome in 20 individuals before PTA, and 1, 3, 6, 9
      and 12 months after PTA. In eight cases, rejection was detected while there was
      one case of glomerulonephritis in the graft during the follow-up period.
      Evaluation (AUCCcr)0-12 related to the integrated pre-PTA value of Ccr [(Ccr)0 x
      12] revealed a rise in GFR by more than 20 % in 65 % of cases. No improvement was
      observed in seven individuals with post-PTA complications. When assessing the
      integrated value of MAP, success of PTA (a reduction by at least 10 %) was found
      in 85 % of cases. No significant correlation was found between the relative
      changes of integrated GFR and MAP. Our data suggest that evaluation of the
      integrated value of GFR or MAP on the basis of AUC0-t allows to characterize, in
      a simple manner, the level of graft function and MAP throughout the follow-up
      period in individual cases. Furthermore, it may provide additional information on
      the average values obtained at different time intervals after the therapeutic
      procedure.

PMID- 11252529
TI  - Baroreflex sensitivity determined by spectral method and heart rate variability,
      and two-years mortality in patients after myocardial infarction.
AB  - Sympathetic overactivity and low parasympathetic activity is an autonomic
      dysfunction (AD) which enhances cardiac mortality. In the present study, the
      impact of AD on the mortality in patients after myocardial infarction was
      evaluated. We examined 162 patients 7-21 days after myocardial infarction, 20
      patients of whom died in the course of two years. Baroreflex sensitivity (BRS)
      was estimated by spectral analysis of spontaneous fluctuations of systolic blood
      pressure and cardiac intervals (Finapres, 5 min recording, controlled breathing
      20/min). The heart rate variability was determined as SDNN index (mean of
      standard deviations of RR intervals for all 5-min segments of 24-hour ECG
      recordings). BRS < 3 ms/mm Hg and/or SDNN index < 30 ms were taken as markers of
      AD. The risk stratification was performed according to the number of the
      following standard risk factors of increased risk of cardiac mortality (SRF):
      ejection fraction < 40%, positive late potentials and the presence of ventricular
      extrasystoles > 10/h. No difference in mortality between patients with AD (4%)
      and without AD (4.5%) was found in 92 patients without SRF, the mortality in 6
      patients with three SRF was 66.6%. Five of these patients had AD. Out of 64
      patients with one or two SRF, 32 had AD. The mortality of patients without AD was
      6.25% and 31.2% of those with AD (p<0.025). It is concluded that AD enhanced two
      years mortality five fold in our patients with moderate risks.

PMID- 11252530
TI  - Effect of diet and 677 C-->T 5, 10-methylenetetrahydrofolate reductase genotypes
      on plasma homocyst(e)ine concentrations in slovak adolescent population.
AB  - The objective of this study was to evaluate the effect of diet and 677 C-->T
      mutation of the methylenetetrahydrofolate reductase (MTHFR) gene on plasma
      homocyst(e)ine concentrations in an adolescent population (113 males, age: 14.2+/
      2.4 years; 202 females, age: 14.9+/-2.1 years) from a region characterized by
      high cardiovascular mortality. Homocyst(e)ine levels did not differ between males
      and females (9.4+/-3.5 and 8.9+/-3.1 micromol/l, respectively). The homozygosity
      for the 677 C-->T MTHFR mutation was found in 4.6 % of subjects. No differences
      in homocyst(e)ine levels were found between MTHFR genotypes. Analysis of the diet
      composition which was performed on a 24-hour daily recall basis and a food
      frequency questionnaire showed a low daily intake of vitamin B6 (males: 1.13
      mg/66% RDA; females: 0.92 mg/61% RDA). Daily folic acid intake was 0.21 g/105%
      RDA in males and 0.23 g/115% RDA in females. The results of our study show that
      the high homocyst(e)ine levels in the adolescent population were not affected by
      the 677 C-->T MTHFR mutation. We conclude that an insufficient dietary intake of
      vitamin B6 and folic acid is responsible for this finding. This is in accord with
      the recommendation that the dietary allowances for folate should be reset to the
      originally prescribed levels of 0.4 g/day which should be sufficient to control
      the homocysteine levels.

PMID- 11252531
TI  - Brain activation during volitional control of breathing.
AB  - Functional magnetic resonance imaging (fMRI) was used to demonstrate the brain
      activation during volitional control of breathing in nine healthy human subjects.
      This type of breathing was induced by acoustic stimuli dictating the respiratory
      frequency. During the period of dictated breathing not only the frontal and
      temporal lobes of the brain, but also the parietal lobes were bilaterally
      activated. The frontal lobe was activated bilaterally in all subjects, with
      frequent activation of Brodmann areas 4 and 6. In the parietal lobe, activation
      could mostly be demonstrated in gyrus postcentralis and the same was true for
      area 22 in the temporal lobe.

PMID- 11252532
TI  - Humoral and cellular immune responses in gluten-treated suckling or hand-fed
      rats.
AB  - We analyzed the immune response to gliadin in suckling rats and rats hand-fed
      with an artificial milk formula, an animal model of gluten enteropathy. Animals
      of both groups were intragastrically given either gliadin or albumin (control
      animals) or gliadin from birth till day 55. When compared to the controls, spleen
      lymphocytes from both groups of gliadin-treated rats cultivated in vitro
      exhibited a significant increase of spontaneous 3H-thymidine incorporation.
      Moreover, the proliferation of spleen and mesenteric lymph node (MLN) lymhocytes
      from both groups of gliadin-treated suckling and hand-fed rats was specifically
      increased by the in vitro gliadin challenge. Spleen B cells from gliadin-treated
      rats spontaneously produced higher amounts of gliadin-specific antibodies than
      those from the controls, however, in vitro stimulation by gliadin caused no
      further increase in antibody production. Apoptotic DNA fragmentation in MLN cells
      was higher in gliadin-treated rats than in albumin-treated ones, independently of
      the milk diet during the suckling period.

PMID- 11252533
TI  - Somatotropin has no effect on the quantity of guanine nucleotide binding proteins
      Gqalpha/G11alpha in goat adipose tissue in vivo.
AB  - The decapeptide QLNLKEYNLV corresponding to the C-terminus of Gq/G11alpha guanine
      nucleotide-binding proteins (G-proteins) was synthesized by the solid-phase
      method and conjugated to keyhole limpet hemocyanin. The rabbits were immunized
      with these conjugates and an antiserum that reacted specifically with the alpha
      subunit of Gq/G11 proteins was used in this study. The antiserum exhibited no
      cross-reactivity with the alpha subunits of stimulatory (Gs) or inhibitory (Gi) G
      proteins associated with adenylate cyclase. Immunoblots with the antiserum showed
      that it specifically recognized the Gq/G11 alpha-proteins in cholate extracts of
      adipose tissue membranes of goats. Treatment of young castrated male goats with
      bST had no effect on the quantity of Gq/G11 alpha subunits in adipose tissue and
      the results thus obtained did not support the idea that the bST signal in adipose
      tissue is transmitted via Gq/G11 alpha-proteins.

PMID- 11252534
TI  - Serum leptin levels in patients with sideropenic and pernicious anemia: the
      influence of anemia treatment.
AB  - Leptin is a 16 kDa protein hormone involved in food intake, energy expenditure
      regulation and numerous other physiological processes. Recently, leptin has been
      demonstrated to stimulate hematopoietic stem cells in vitro. The aim of our study
      was to measure serum leptin and erythropoietin levels in patients with
      sideropenic (n = 18) and pernicious anemia (n=7) before and during anemia
      treatment. Blood samples for the blood count, leptin and erythropoietin
      determinations were obtained by venepunction at the time of the diagnosis of
      anemia and after partial and complete anemia recovery. The relationships of serum
      leptin levels to erythropoietin levels and blood count parameters were also
      studied. No significant differences in serum leptin levels between the groups
      studied were found. The serum leptin levels in none of groups were modified by
      treatment of anemia (basal levels, the levels during treatment and after anemia
      recovery were 13.1+/-14.5 vs 12.8+/-15.6 vs 12.0+/-14.8 ng/ml in patients with
      sideropenic anemia and 7.8+/-8.5 vs 9.5+/-10.0 vs 8.9+/-6.6 ng/ml in patients
      with pernicious anemia). The erythropoietin levels were higher at the time of
      anemia in both groups and decreased significantly after partial or complete
      recovery. Serum leptin levels in both groups correlated positively with the body
      mass index. No significant relationships were found between serum leptin levels
      and erythropoietin values or various parameters of the peripheral blood count. We
      conclude that serum leptin levels in patients with sideropenic and pernicious
      anemia positively correlate with the body mass index but are not influenced by
      the treatment of anemia.

PMID- 11252535
TI  - Effects of transdermal application of DHEA on the levels of steroids,
      gonadotropins and lipids in men.
AB  - In order to ascertain the kinetics of absorption and metabolism of transdermally
      administered dehydroepiandrosterone (DHEA), 10 men 29-72 years old (mean 52.4+/
      14.5) received 50 mg DHEA/day in a gel applied onto the skin of the abdomen for 5
      consecutive days. The objective was to establish the extent to which DHEA
      influences the levels of gonadotropins, sex hormone-binding globulin and lipids.
      It was found that DHEA is well absorbed and rapidly metabolized to its sulfate
      (DHEAS), androstenedione, and consequently to testosterone and estradiol. The
      DHEA levels that markedly increased after the first doses gradually declined
      already during the application, and this decline proceeded even after it was
      discontinued, reaching levels significantly lower than the original ones. On the
      other hand, the levels of DHEA metabolites (with the exception of DHEAS) rose
      during the application and reached values significantly higher than the basal
      ones within 5 weeks. This effect was accompanied by significantly decreased
      levels of LH. The serum levels of lipids, namely of cholesterol (both HDL and LDL
      cholesterol), triglycerides, apolipoproteins A-I and B and lipoprotein(a) after
      DHEA application were not changed significantly, and the atherogenic index (AI)
      remained unaltered. However, some correlations between hormones and lipids were
      found. Negative correlations concerned the following indices: DHEA/Lp(a);
      DHEAS/cholesterol; DHEA, DHEAS, testosterone/TG; testosterone/AI. On the other
      hand, LH, FSH/cholesterol, FSH, SHBG/LDL cholesterol, FSH/Apo B, Lp(a) correlated
      positively. It can be concluded that transdermal short-time application of DHEA
      results in a decrease of endogenous DHEA after finishing the treatment, with a
      parallel marked increase in the levels of sex hormones. Using this application
      protocol, exogenous DHEA neither altered the lipid spectrum, nor did it influence
      the atherogenic index.

PMID- 11252536
TI  - STESYS2: extended STESYS software for MS Windows.
AB  - The STESYS2 software is a new version of the IBM PC software supporting
      interactive stereological measurements. In comparison with the previous STESYS,
      it is enhanced by a number of useful options, e.g. on-line image input via a TV
      camera coupled with a microscope operating under MS Windows OS. The main
      advantage, when compared with other such software packages, is the design of the
      STESYS2 as a module of the freeware image processing system Image Tool which
      provides a user-friendly environment including a number of image processing and
      preprocessing routines. Capabilities of the STESYS2 are illustrated by a
      practical example: estimation of the surface area of capillaries in the terminal
      villi of human placenta by the Sandau spatial grid method.

PMID- 11252537
TI  - Recovery of peripheral blood cells in irradiated mice pretreated with bacterial
      extract IRS-19.
AB  - The effect of antigenic bacterial lysate IRS-19 on the recovery of blood cells
      was studied in mice injured by a single dose of 7 Gy irradiation. The
      preirradiation administration of IRS-19 accelerated the recovery of leukocytes,
      reticulocytes and platelets in peripheral blood. The recovery of leukocytes 9-14
      days after irradiation in protected animals was accompanied by a higher level of
      band forms of granulocytes as well as activated lymphoid and monocytoid cells.

PMID- 11252538
TI  - Relation of ventricular fibrillation threshold to heart rate during normal
      ventilation and hypoventilation in female Wistar rats: a chronophysiological
      study.
AB  - The aim of our study was to verify the relationship between heart rate (HR) and
      ventricular fibrillation threshold (VFT) during different types of ventilation in
      female Wistar rats from the circadian point of view. The experiments were
      performed under pentobarbital anesthesia (40 mg/kg i.p., adaptation to a light
      dark cycle 12:12 h, open chest experiments) and the obtained results were
      averaged independently of the seasons. The VFT measurements were performed during
      normal ventilation (17 animals) and hypoventilation (10 animals). The HR was
      recorded immediately before the rise of ventricular arrhythmias. Results are
      expressed as arithmetic means -/+ S.D. and differences are considered significant
      when p<0.05. The basic periodic characteristics were calculated using single and
      population mean cosinor tests. The results from our experiments have demonstrate
      that 1) the VFT and HR respond identically to hypoventilation by a decrease in
      the light and also in the dark phases, and 2) hypoventilation changes the 24-h
      course of the VFT without a change in the 24-h rhythm of the HR. It is concluded
      that the HR and VFT behave as two independent functional systems without apparent
      significant circadian dependence during both types of ventilation.

PMID- 11252539
TI  - Influence of intrauterine undernutrition on the development of
      hypercholesterolemia in an animal model.
AB  - A low birth weight is a new risk factor for the development of premature
      atherosclerosis. The effect of intrauterine undernutrition on
      hypercholesterolemia in later life was studied in an experimental model using the
      Prague Hereditary Hypercholesterolemic (PHHC) rat. Compared to animals in the
      control group (Wistar rats), animals with an increased sensitivity to high
      cholesterol diet (PHHC rats) display hypercholesterolemia. Only in PHHC animals,
      individuals undernourished in their intrauterine life (hypotrophic group, HG) had
      a significantly higher total cholesterol, compared with individuals without food
      restriction in pregnancy (eutrophic group, EG). Restricted food intake in
      pregnancy led to smaller nests and a decreased number of pups in each litter. We
      found no significant diferences in birth weight between HG and EG. In spite of
      similar birth weights in PHHC and Wistar rats, intrauterine undernutrition caused
      an increase in cholesterolemia in the HG group of the PHHC rats. The effect of
      intrauterine undernutrition on the development of hypercholesterolemia will most
      likely play a role in individuals with geneticaly determined increased
      susceptibility to a high-cholesterol diet. The use of this model of intrauterine
      undernutrition for the study of hypercholesterolemia has proved to be feasible.

PMID- 11252540
TI  - Inhibitory effect of FK 506 and cyclosporin A on nitric oxide production by LPS
      treated cultured rat macrophages.
AB  - We analyzed the effect of FK 506 on the production of nitric oxide by
      macrophages. Isolated rat peritoneal macrophages were cultured for 24 h with or
      without lipopolysaccharide (LPS) (5 microg/ml) and in the absence or presence of
      FK 506 (0.1 and 1 microg/ml). The concentration of NO2- in culture supernatants
      was taken as a measure of nitric oxide production. FK 506 (0.1 and 1 microg/ml)
      reduced the LPS-induced increase of NO2- levels by 68% and 81%, respectively. The
      impact of cyclosporin A (CsA) was studied in order to compare their effects. CsA
      (0.1 and 1 microg/ml) decreased the levels of nitrites by 39% and 69%,
      respectively. The results obtained suggest that both immunosuppressive drugs
      exhibit a dose-dependent inhibitory effect on nitric oxide production and that FK
      506 is a more potent agent than CsA in this respect.

PMID- 11252541
TI  - Cardiovascular changes during sudden ascent in a cable cabin to the moderate
      altitude.
AB  - Our aim was to test the hypothesis that the occurrence of extrasystoles in higher
      decennia is proportional to the altitude. The occurrence of supraventricular
      (SVPB) and ventricular (VEB) extrasystoles, values of systolic and diastolic
      blood pressure and the heart rate were studied in 20 healthy elderly men (50-64
      years) during cable cabin transportation to a moderate altitude. These values
      were measured in stations located at 898 m, 1764 m, and 2632 m above sea level
      during the transportation in both directions. Our records show that the values of
      blood pressure and heart rate were within normal limits during the whole period
      of transportation. Both SVPB and VEB were increasing during the ascent and
      decreasing to the initial values during the descent compared to the values at
      altitude of 898 m. The highest values (6 to 7-times exceeding the initial ones)
      were measured at the summit. The results have demonstrated that the occurrence of
      SVPB and VEB is proportional to the altitude. The increased incidence in the
      number of extrasystoles is suggested to be mediated by beta-adrenoceptors.

PMID- 11252542
TI  - Ozone-induced micronuclei frequency in rat alveolar Type II cells.
AB  - The effect of ozone, a ubiquitous air pollutant, was tested on cultured pulmonary
      epithelial type II cells isolated from rats. After 40-hour culture, the cells
      were exposed for 6 h to 400 ppb of ozone or air. The number of micronucleated
      cells was counted after the exposure. In each group, 17000 cells were evaluated.
      The number of micronucleated cells was significantly increased in the ozone
      exposed group (12.24 per 1000 cells) compared to the control group (5.00 per 1000
      cells). The results showed the mutagenic effect of ozone exposure on alveolar
      type II cells, manifested in the increased frequency of their micronuclei.

PMID- 11252544
TI  - Enteroviral meningitis. Cost of illness and considerations for the economic
      evaluation of potential therapies.
AB  - With limited financial resources available, it is now becoming more acceptable to
      evaluate medical innovations in terms of incremental economic value. The purpose
      of this paper is to provide an overview of enteroviral meningitis and to
      summarise the economic literature to identify relevant costs and outcomes.
      Enteroviral meningitis is the most common cause of aseptic meningitis, and occurs
      in 4.5 to 30 per 100,000 population annually with a duration of illness lasting
      between 1 and 2 weeks after onset of initial symptoms. The major resource
      categories that contribute to the overall direct costs of management of
      enteroviral meningitis include physician visits, hospital admissions, emergency
      room visits, medications, procedures such as lumbar puncture and computed
      tomography scans, re-hospitalizations and follow-up physician visits. Indirect
      costs are incurred in terms of school or work days missed or restrictions in
      daily activities. The total direct costs of an episode of enteroviral meningitis
      range from $US450 for outpatients to $US5093 for inpatient management (1996
      values). The total indirect costs of an episode of enteroviral meningitis are
      estimated to be equivalent to 5 to 7 activity-restricted days. Interventions that
      improve early diagnosis or decrease the duration and need for hospitalisation
      will significantly affect the cost of managing enteroviral meningitis. Additional
      prospective studies are needed to study the impact of interventions on the burden
      of enteroviral meningitis.

PMID- 11252543
TI  - The cost of HIV treatment and care. A global review.
AB  - This review of published studies on the costs of HIV treatment and care describes
      some of the recent developments that have influenced these costs in
      industrialised and industrialising countries, especially within the context of
      changing drug treatments. Some of the different approaches to estimating the
      economic impact of HIV infection are briefly presented. The methods used to
      review the literature are described, particularly the criteria of a scoring
      system that was specifically developed to systematically screen some of the
      studies identified. The mean review score for studies dealing with direct
      hospital costs increased significantly (p = 0.003) over the 3 periods analysed
      (before 1987, 1987 to 1995, and 1996 and beyond), indicating that the overall
      'quality' of studies increased over time. All cost estimates, other than those
      from non-industrialised regions, were converted to 1996 US dollars using country
      specific total health expenditure inflaters and country-specific Gross Domestic
      Product Purchasing Power Parity converters. A summary of hospital cost estimates
      over time and by region demonstrated that the costs of treating asymptomatic
      individuals and people with symptomatic non-AIDS increased over the period, but
      that the costs of treating individuals with AIDS appears to have stabilised since
      the late 1980s. As fewer studies could be identified on the costs of community
      and informal care, indirect productivity costs and population cost estimates, and
      costs of care for children with HIV infection, all of these studies were reviewed
      without the use of the scoring system. Finally, the discussion explores the
      evidence on the global costs of HIV in non-industrialised economies and the
      affordability of HIV treatment and care. Some suggestions for the direction of
      future HIV costing studies are also presented. A need remains for good quality
      cost data. Adequate research effort should be directed to improving the scope and
      quality of information on costs of HIV service provision around the world.

PMID- 11252545
TI  - Glycoprotein IIb/IIIa receptor therapy in percutaneous coronary intervention and
      non-ST-segment elevation acute coronary syndromes. Estimating the economic
      implications.
AB  - In addition to efficacy and safety, cost is an important determinant of the use
      of glycoprotein IIb/IIIa (GPIIb/IIIa) therapy in patients with acute coronary
      syndromes (ACS) or undergoing percutaneous coronary intervention (PCI). In PCI,
      the average procurement cost of GPIIb/IIIa therapy ranges from $US400 to $US1500
      (1999 values) per patient treated, depending on agent, dose and duration of
      infusion. Prospective economic substudies with abciximab and tirofiban have
      demonstrated subsequent cost savings that partially offset the procurement costs
      of the agents. The drug procurement costs per death or myocardial infarction (MI)
      prevented in PCI appear to vary from $US10,500 to $US37,000, depending on the
      agent. Abciximab has been proven to provide a survival benefit in the setting of
      PCI, including coronary stenting. Analyses of abciximab use yield cost
      effectiveness ratios of $US2875 to $US14,765 per life-year or quality-adjusted
      life-year saved, which compares favourably with most widely accepted therapies.
      In non-ST-segment elevation ACS, drug procurement costs range from $US700 to
      $US1700 per patient treated, also depending on agent, dose and duration of
      infusion. Evidence of cost offsets from changes in subsequent resource
      utilisation are limited and seem contingent upon a conservative risk
      stratification approach. Drug procurement costs have been calculated as $US32,000
      to $US82,000 per death or MI prevented in the ACS trials. Cost-effectiveness
      ratios of $US16,000 per life-year saved for the US and Western European cohorts
      in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression
      Using Integrilin Therapy (PURSUIT) trial are favourable. If these analyses prove
      correct, the cost effectiveness of GPIIb/IIIa receptor therapy for patients with
      non-ST-segment elevation ACS will also compare favourably with other widely
      accepted therapies in industrialised countries. More clinical and economic data
      are necessary to allow better selection of specific patients who will receive the
      most benefit from GPIIb/IIIa therapy in healthcare systems with limited
      resources.

PMID- 11252546
TI  - Dermatan sulfate versus unfractionated heparin for the prevention of venous
      thromboembolism in patients undergoing surgery for cancer. A cost-effectiveness
      analysis.
AB  - BACKGROUND: In a recent clinical trial, dermatan sulfate was found to be more
      effective than unfractionated heparin (UFH), but equally well tolerated, for the
      prevention of deep vein thrombosis (DVT) after major surgery for cancer.
      OBJECTIVE: To perform a cost-effectiveness analysis of dermatan sulfate versus
      UFH in this clinical setting. DESIGN AND SETTING: This was a retrospective
      economic analysis using data from a randomised clinical trial, and was performed
      from the hospital perspective. METHODS: Clinical event rates were extrapolated
      from the observed venographic DVT rates, using appropriate assumptions from the
      scientific literature. The economic effects of switching DVT prophylaxis from UFH
      to dermatan sulfate and the potential lives saved were assessed by a predictive
      decision model. RESULTS: The per patient cost, including the burden of residual
      thromboembolic events and major bleeding complications, was estimated to be 154
      euros (EUR) for dermatan sulfate and EUR185 for UFH (1998 values). With reference
      to a potential target population of 60,000 patients/year undergoing surgery for
      cancer in Italy, the total prophylaxis-associated cost was EUR9,258,000 for
      dermatan sulfate and EUR11,096,000 for UFH, whereas the potential deaths from
      prophylaxis failure were 204 and 392, respectively. This represented a saving of
      EUR1,838,000 and 188 potential lives per year with the dermatan sulfate option.
      The final costs and effects were mainly sensitive to variations in the rates of
      DVT and pulmonary embolism, and to the possible need for 1 extra day of
      hospitalisation because of the earlier preoperative initiation of dermatan
      sulfate prophylaxis. CONCLUSION: Dermatan sulfate is more cost effective than UFH
      for the prevention of postoperative venous thromboembolism in patients with
      cancer. If the hospital stay needs to be prolonged, then the dermatan sulfate
      option may involve a small additional cost (EUR47) per potential life saved.

PMID- 11252547
TI  - A general model of the effects of sleep medications on the risk and cost of motor
      vehicle accidents and its application to France.
AB  - BACKGROUND: Although various prescription drugs may be equally effective in
      promoting sleep, some may lead to substantial impairment in psychomotor
      functioning and an increased risk of motor vehicle accidents. OBJECTIVE: To
      develop a general model to evaluate the potential effects of sleep medications on
      motor vehicle accidents and costs, and apply the model to the French setting.
      METHODS: Impairment in driving performance, as evaluated by randomised controlled
      open-road studies using the standard deviation of a vehicle's lateral position
      (SDLP), a measure of weaving, was expressed in terms of equivalent blood alcohol
      (ethanol) concentration (BAC). Epidemiological data were then used to relate BAC
      to the excess risk of motor vehicle accidents. Although a non-impairing
      medication would not increase risk, a medication that produces mild impairment in
      driving performance (a change of 2.5 cm in SDLP, equivalent to 0.05% BAC) would
      increase motor vehicle accident risk by 25%. One that leads to moderate
      impairment (an SDLP change of 4.5 cm, equivalent to 0.08% BAC) would roughly
      double this risk, and a severely impairing medication (an SDLP change of 7 cm,
      equivalent to 0.12% BAC) would result in up to a 5-fold increase in motor vehicle
      accident risk. For application to the French setting, a hypothetical cohort of
      100,000 adult drivers with insomnia was assumed to be treated for 14 days either
      with zaleplon 10 mg, a new sleep medication that has been shown not to
      significantly impair driving performance, or zopiclone 7.5 mg, which has been
      shown to cause moderate impairment. RESULTS: Compared with zaleplon, use of
      zopiclone over 14 days in France would be expected to result in 503 excess
      accidents per 100,000 drivers at an additional cost of 158 French francs (31 US
      dollars) per person (1996 values). CONCLUSIONS: Our model illustrates the extent
      to which non-impairing sleep medications could reduce the burden posed by motor
      vehicle accidents. Our model is designed to be general, and thus can serve as the
      basis for similar investigations.

PMID- 11252549
TI  - Economic analysis of initial HIV treatment. Efavirenz- versus indinavir
      containing triple therapy.
AB  - OBJECTIVE: To compare the clinical and economic outcomes associated with triple
      therapy containing efavirenz or indinavir and 2 nucleoside reverse transcriptase
      inhibitors (NRTIs; zidovudine and lamivudine) in HIV-positive patients. DESIGN
      AND SETTING: An economic model based on viral load and CD4+ cell counts to
      predict long term outcomes such as progression to AIDS and AIDS-related death was
      developed and then analysed using data from a randomised clinical trial. Cost
      estimates from the healthcare system perspective were based on data from 6 state,
      all-payor databases, the AIDS Cost and Services Utilisation Study, and other
      literature. Analyses were carried out for time horizons between 5 and 15 years.
      PATIENTS AND INTERVENTIONS: HIV-positive patients with limited exposure to NRTIs.
      Initial regimens consisted of efavirenz or indinavir, each combined with 2 NRTIs.
      A maximum of 2 switches to other regimens was permitted. MAIN OUTCOME MEASURES
      AND RESULTS: The efavirenz-containing triple therapy regimen was predicted to
      prolong survival at a savings of up to 10,923 US dollars (1998 values) relative
      to initial therapy with the indinavir-containing regimen. Patients who receive
      efavirenz are expected to have 11% greater survival at 5 years and fewer
      treatment failures (28 vs 52%, at 2 years). Overall, the economic and health
      benefits predicted for the efavirenz-containing regimen were robust to reasonable
      variation in key parameters. CONCLUSIONS: The superior clinical trial outcomes
      for efavirenz-containing regimens should translate into substantial economic and
      health benefits.

PMID- 11252548
TI  - Cost efficacy of tazobactam/piperacillin versus imipenem/cilastatin in the
      treatment of intra-abdominal infection.
AB  - OBJECTIVE: To compare the cost, efficacy and cost efficacy of
      tazobactam/piperacillin and imipenem/cilastatin in the treatment of intra
      abdominal infection. DESIGN: The analysis was retrospective and based on a
      decision tree. Effectiveness data were obtained from 19 published clinical
      trials. Direct costs were quantified per patient from the time the decision was
      made to administer the antibacterial to the end of the first course of treatment
      or the end of a subsequent course of treatment, if required. The primary end
      point was the cost per successfully treated patient. The cost per life saved was
      also analysed. Various follow-up times were taken into account. PERSPECTIVE:
      German National Health Insurance funds. STUDY POPULATION: 1744 patients with
      intra-abdominal infection. INTERVENTIONS: Tazobactam/piperacillin (total daily
      dosage of 13.5 g/day) and imipenem/cilastatin (total daily dosage of 1.5 to 4
      g/day). The mean duration of treatment varied from 5.5 to 8.2 days for
      tazobactam/piperacillin and 5 to 9.4 days for imipenem/cilastatin. MAIN OUTCOME
      MEASURE AND RESULTS: Compared with imipenem/cilastatin, treatment with
      tazobactam/piperacillin was more effective and the overall treatment costs were
      lower. In the base-case analysis, the cost-efficacy ratio (cost per successfully
      treated patient) was 7881 German deutschmarks (DM) for tazobactam/piperacillin
      and DM11,390 for imipenem/cilastatin. The incremental cost-efficacy ratio (per
      life saved) varied between -DM72,567 and -DM350,738 for tazobactam/piperacillin.
      Sensitivity analyses revealed that the results were robust against various
      assumptions on cost parameters, clinical outcomes and length of treatment. All
      costs reflect 1998 values; $US1 = DM1.85. CONCLUSIONS: This study suggests that
      compared with imipenem/cilastatin, tazobactam/piperacillin is more cost
      efficacious in the treatment of intra-abdominal infections and that it offers a
      cost advantage through fewer relapses and lower daily therapeutic costs.

PMID- 11252550
TI  - Index 2000.

PMID- 11252551
TI  - Dissociability, modularity, evolvability.

PMID- 11252553
TI  - Of coiled oysters and big brains: how to rescue the terminology of heterochrony,
      now gone astray.
AB  - During the past decade, the terminology of heterochrony, heretofore consistent
      and workable, has become internally illogical and incoherent as the unfortunate
      result of an extension of terms, properly devised to describe shifts in
      developmental timing of shapes and features, to the rates and timings that cause
      these shifts. All the resulting, and extensive, confusion in the literature
      arises as a pure consequence of this error in logic and nomenclature, and not at
      all from disagreement about the important empirical questions described by this
      central concept and phenomenon in the integration of evolution and development.
      In particular, the claim that the same feature in human evolution (the
      paedomorphic shape of the human cranium) expresses either neoteny or the
      apparently opposite phenomenon of hypermorphosis only records the terminological
      error, and not any factual disagreement-for this neotenic feature has probably
      arisen by a prolongation of juvenile growth patterns inappropriately designated
      as "hypermorphosis of rate." I show that a prominent and unchallenged case of
      neoteny in fossil oysters arises by exactly the same evolutionary mode. When we
      restore the terminology of heterochrony by the "paedomorphic" intellectual event
      of dropping these inadaptive terminal accretions (the illogical extension of
      shape categories to describe rates), then the concept of heterochrony will again
      make proper distinctions by designating a clearly meaningful category of
      evolutionary changes originating by shifts in timing for features already present
      in ancestors. "It's not all het- erochrony"-and this particular statement of
      "less is more" represents heterochrony's strength as an interesting subset with
      definite meaning, rather than an illogical hodge-podge apparently applicable to
      all phenomena, and therefore explaining nothing.

PMID- 11252552
TI  - What constitutes a 'large' mutational change in phenotype?

PMID- 11252554
TI  - Developmental constraints on an adaptive plasticity: reaction norms of
      pigmentation in adult segments of Drosophila melanogaster.
AB  - Variation of dark pigmentation according to developmental temperature was
      investigated in two geographic populations (France and India) with the isofemale
      line technique (20 lines for each population). The response curves called the
      reaction norms, were established in females for seven different segments: the
      mesothorax and abdomen segments 2-7 (Abd 2-7). In all cases the response curves
      were non-linear and had to be described either by a quadratic convex polynomial
      for thorax and Abd 2-5, or by a cubic polynomial for Abd 6 and 7. Among abdomen
      segments, increasing antero-posterior gradients were observed for several traits,
      including average pigmentation, overall phenotypic plasticity, the temperature of
      minimum pigmentation, and the curvature parameter of quadratic norms. Genetic
      correlations between abdomen segments were high when adjacent segments were
      considered, but became nil when more distant segments were correlated, suggesting
      that different pigmentation genes are expressed in the anterior and the posterior
      part of the abdomen. Characteristic values of reaction norms provided information
      either on trait value (i.e., the extension of pigmentation) or on plasticity.
      Correlations between plasticity and pigmentation were generally low and non
      significant, suggesting their genetic independence. The overall darker
      pigmentation which is observed at low temperatures is assumed to be an adaptive
      plasticity. However, the differences which are evidenced among segments reveal
      strong interactions with developmental genes. These interactions are less likely
      to be a consequence of natural selection and are better interpreted as
      developmental constraints. The reaction norms analysis reveals the complexity of
      these interactions and should help, in the future, in the identification of the
      responsible thermosensitive genes.

PMID- 11252555
TI  - Maternal expression and early zygotic regulation of the Hox3/zen gene in the
      grasshopper Schistocerca gregaria.
AB  - In insects, a key step in the early patterning of the egg is to distinguish the
      primordium of the embryo proper from those regions that will form extra-embryonic
      membranes. In Drosophila, where these processes are well understood, the
      structure of the extra-embryonic membranes is highly derived. The distinct amnion
      and serosa typical of lower insects is replaced by a single, fused, and much
      reduced membrane, the amnioserosa, which never secretes an embryonic cuticle. We
      have used the Zen gene as a marker to study the formation of the extra-embryonic
      membranes, and other aspects of early embryonic patterning, in the grasshopper
      Schistocerca gregaria (African Plague Locust). Zen genes are derived from Hox
      genes, but in Drosophila they appear to have lost any role in patterning the A/P
      axis of the embryo; instead, they are involved in D/V patterning and the
      specification of the extra-embryonic membranes. We show that the Schistocerca zen
      gene is expressed during embryogenesis in three distinct phases. The first of
      these is during cleavage, when Sgzen is transiently expressed in all energids
      that reach the cell surface. The second phase of expression initiates in a ring
      of "necklace cells" that surround the forming embryo, and demarcate the boundary
      between the amnion and serosa. This leads to expression throughout the serosa.
      The final phase of expression is in the amnion, after this has separated from the
      serosa. This complex pattern implies that the role of Sgzen in Schistocerca is
      not limited solely to the specification of cell identity in the extra-embryonic
      membranes. We also report that the Schistocerca zen gene is expressed maternally,
      unlike its Drosophila and Tribolium counterparts. A distinct maternal transcript,
      and maternal Zen protein, accumulate in the developing oocyte from early post
      meiotic stages. They remain uniformly distributed in the oocyte cytoplasm until
      late vitellogenic stages, when the protein and RNA become somewhat concentrated
      at the egg cortex and in the posterior polar cap of the oocyte, probably by
      passive exclusion from the yolk. The cytoplasmic localization of Sgzen protein in
      the oocyte, and at some stages during embryogenesis, implies that nuclear
      exclusion of this transcription factor is specifically controlled.

PMID- 11252556
TI  - Embryonic expression patterns of the Hox genes of the crayfish Procambarus
      clarkii (Crustacea, Decapoda).
AB  - Higher crustaceans (class Malacostraca) represent the most species-rich and
      morphologically diverse group of non-insect arthropods. The superorders Eucarida
      and Peracarida, two large groups that separated over 350 million years ago,
      encompass most malacostracan diversity. Recently, the Hox genes of the peracarid
      woodlouse Porcellio scaber(Isopoda) were shown to be expressed in domains that
      coincide with morphological boundaries of body tagmata, which differ from those
      in insects (Abzhanov and Kaufman 1999a,b). Moreover, observed changes in Hox
      expression domains during ontogeny correlate with morphological remodeling, such
      as a transformation of the first thoracic leg into mouthpart maxillipeds, which
      occurs in the trunk of the embryo. Decapods have a different modification of the
      malacostracan bodyplan, with up to three pairs of maxillipeds and extensive
      fusion and cephalization of the thorax. Here we describe expression patterns of
      the trunk Hox genes Scr, Antp, Ubx, abd-A and cad in the eucarid crayfish
      Procambarus clarkii (Decapoda). We find that the crayfish expression patterns,
      for the most part, resemble those of the woodlouse Porcellio scaber(Isopoda), but
      are more modulated and complex. Nevertheless, as in Porcellio the boundaries of
      the Hox expression domains do correlate with morphological features and their
      modulations to transformations in the embryo. Thus we propose that the trunk Hox
      genes were likely important in the evolution of and currently play an essential
      role in the development of the complex decapod bodyplan.

PMID- 11252557
TI  - The amphioxus Hox cluster: deuterostome posterior flexibility and Hox14.
AB  - The amphioxus (Branchiostoma floridae) Hox cluster is a model for the ancestral
      vertebrate cluster, prior to the hypothesized genome-wide duplications that may
      have facilitated the evolution of the vertebrate body plan. Here we describe the
      posterior (5') genes of the amphioxus cluster, and report the isolation of four
      new homeobox genes. Vertebrates possess 13 types of Hox gene (paralogy groups),
      but we show that amphioxus possesses more than 13 Hox genes. Amphioxus is now the
      first animal in which a Hox14 gene has been found. Our mapping and phylogenetic
      analysis of amphioxus "Posterior Class" Hox genes reveals that these genes are
      evolving at a faster rate in deuterostomes than in protostomes, a phenomenon we
      term Posterior Flexibility.

PMID- 11252559
TI  - Evo-devo or devo-evo--does it matter.

PMID- 11252558
TI  - Expression of a Scr/Hox5 gene in the larval central nervous system of the
      gastropod Haliotis, a non-segmented spiralian lophotrochozoan.
AB  - Hox genes encode a set of evolutionarily conserved transcription factors that
      regulate anteroposterior patterning mechanisms in insects and vertebrates and are
      expressed along this axis in a range of bilaterians. Here we present the
      developmental expression of a Scr/Hox5 gene in the gastropod mollusc Haliotis. In
      Haliotis, embryogenesis yields a non-feeding trochophore larva that subsequently
      develops into the veliger larva, which possesses many of the characteristics of
      the adult body plan. Quantitative RT-PCR analysis reveals that this gene, which
      is called Hru-Hox5, is first expressed in the trochophore larva. Hru-Hox5
      transcript prevalence increases continually through larval development until
      metamorphic competence develops in the veliger and then again over the first four
      days of metamorphosis. In situ hybridization reveals that larval expression of
      Hru-Hox5 is restricted primarily to the primordial and newly formed branchial
      ganglia, located between the anterior cerebral-pleuropedal ganglionic complex and
      the posterior visceral ganglia. The expression of Hru-Hox5 in the central region
      of the abalone CNS is similar to that observed for its orthologue (Lox20) in the
      leech, suggesting that Hox5 genes were used, along with other Hox genes, to
      pattern the CNS of the ancestral spiralian lophotrochozoan.

PMID- 11252560
TI  - Cranial neural crest cell migration in the Australian lungfish, Neoceratodus
      forsteri.
AB  - A crucial role for the cranial neural crest in head development has been
      established for both actinopterygian fishes and tetrapods. It has been claimed,
      however, that the neural crest is unimportant for head development in the
      Australian lungfish (Neoceratodus forsteri), a member of the group (Dipnoi) which
      is commonly considered to be the living sister group of the tetrapods. In the
      present study, we used scanning electron microscopy to study cranial neural crest
      development in the Australian lungfish. Our results, contrary to those of Kemp,
      show that cranial neural crest cells do emerge and migrate in the Australian
      lungfish in the same way as in other vertebrates, forming mandibular, hyoid, and
      branchial streams. The major difference is in the timing of the onset of cranial
      neural crest migration. It is delayed in the Australian lungfish in comparison
      with their living sister group the Lissamphibia. Furthermore, the delay in timing
      between the emergence of the hyoid and branchial crest streams is very long,
      indicating a steeper anterior-posterior gradient than in amphibians. We are now
      extending our work on lungfish head development to include experimental studies
      (ablation of selected streams of neural crest cells) and fate mapping (using
      fluoresent tracer dyes such as Dil) to document the normal fate as well as the
      role in head patterning of the cranial neural crest in the Australian lungfish.

PMID- 11252561
TI  - Otx1 gene-controlled morphogenesis of the horizontal semicircular canal and the
      origin of the gnathostome characteristics.
AB  - The horizontal semicircular canal of the inner ear is a unique feature of
      gnathostomes and is predated by the two vertical semicircular canals, which are
      already present in lampreys and some fossil, armored jawless vertebrates regarded
      as close relatives of gnathostomes. Inactivation in mice of the orthodenticle
      related gene Otx1 results in the absence of this structure. In bony fishes and
      tetrapods (osteichthyans), this gene belongs to a small multigene family
      comprising at least two orthology classes, Otx1 and Otx2. We report that, as in
      the mouse, xenopus and zebrafish, Otx1- and Otx2-related genes are present in a
      chondrichthyan, the dogfish Scyliorhinus canicula, with an Otx1 expression domain
      in the otocyst very similar to those observed in osteichthyans. A strong
      correlation is thus observed in extant vertebrates between the distribution of
      the horizontal semicircular canal and the presence of an Otx1 ortholog expressed
      in the inner ear, which supports the hypothesis that the absence of this
      characteristic in Otx1-/- mice may correspond to an atavism. The same conclusion
      applies to two other gnathostome-specific characteristics also deleted in Otx1-/-
      mice, the utriculosaccular duct and the ciliary process. Together with functional
      analyses of Otx1 and Otx2 genes in mice and comparative analyses of the Otx gene
      families characterized in chordates, these discoveries lead to the hypothesis
      that some of the anatomic characteristics of gnathostomes have appeared quite
      suddenly and almost simultaneously in vertebrate evolution, possibly as a
      consequence of gene functional diversifications following duplications of an
      ancestral chordate gene.

PMID- 11252562
TI  - Barnacle duplicate engrailed genes: divergent expression patterns and evidence
      for a vestigial abdomen.
AB  - Cirripedes (barnacles) are crustaceans that are characterized by a very peculiar
      body plan, in particular by the lack of an abdomen. To study their body plan, we
      searched for their engrailed gene. We found two engrailed (en.a/en.b) genes in
      cirripedes. The two engrailed genes of the rhizocephalan barnacle Sacculina
      carcini are expressed in the posterior compartment of developing segments and
      appendages. When the neuroectoderm differentiates into epidermis and neuroderm
      the expression patterns of en.a and en.b diverge dramatically. en.a expression
      fades in segment epidermis whereas it is subsequently detected ventrally in
      reiterated putative neural cells. At the same time, en.b expression increases in
      the epidermis, which makes it a very good segmentation marker. Five tiny en.b
      stripes are observed between the sixth thoracic segment and the telson. We
      interpret these stripes as the molecular definition of vestigial abdominal
      segments, being the remnant of an ancestral state in keeping with the bodyplan of
      maxillopod crustaceans. engrailedexpression is the first molecular evidence for a
      segmented abdomen in barnacles.

PMID- 11252563
TI  - Modeling the maternal-age dependency of reproductive failure and genetic fitness.
AB  - The offspring of older parents are at a higher risk of suffering low birth
      weights and congenital birth defects that result from mutations and chromosomal
      anomalies. When the defect is paternal in origin, it often can be shown that the
      primary lesion arose during mitotic proliferation of the spermatogonial germ cell
      population. By contrast, germline mosaicism is seldom invoked to explain the age
      dependency of maternally derived aberrations because germline proliferation in
      the ovary is already completed during fetal development. Age-dependent defects of
      maternal origin might, however, be explained in part by the progressive loss of
      oocytes during the mother's reproductive life. A large number of oocytes undergo
      the initial stages of maturation each month, but typically only one completes
      maturation and is ovulated while the majority are discarded, probably by an
      apoptotic mechanism. Here we explore the possibility that the monthly choice of
      oocytes to undergo maturation is influenced by subtle phenotypic characters of
      those oocytes that may bear genetic defects such as trisomy 21. We have generated
      a mathematical model to describe the loss kinetics for such mutant oocytes
      relative to the overall pool of resting oocytes, and we assess evolutionary
      strategies that would favor their utilization faster than, at the same rate as,
      or slower than the normal oocytes. This formulation reveals that the slower-rate
      scheme would effectively diminish the utilization of mutant oocytes in young
      mothers but would increase the risk of related birth defects for older mothers.
      Accordingly, we propose that natural selection should have favored the delayed
      utilization of defective oocytes in a primitive high-mortality culture, but that
      this evolutionary strategy would be outmoded for modern society, because it would
      lead to an increased frequency of birth defects for older mothers.

PMID- 11252564
TI  - Evolution of animal body plans: the role of metazoan phylogeny at the interface
      between pattern and process.
AB  - Comprehensive integrative studies are the hallmark of evolutionary developmental
      biology. A properly defined phylogenetic framework takes a central place in such
      analyses as the meeting ground for observation and inference. Molecular
      phylogenies take this place in many current studies on animal body plan
      evolution. In particular, 18S rRNA/DNA sequence analyses have yielded a new view
      of animal evolution that is often contrasted with a presumed traditional or
      classical view. First, I expose this traditional view to be a simplified
      historical abstraction that became textbook dogma. Second, I discuss how two
      recent important studies of animal body plan evolution, examining the evolution
      of the platyhelminth body plan and the evolutionary significance of indirect
      development and set-aside cells, have actively incorporated two problematic
      aspects of the newly emerging molecular view of animal evolution: incomplete and
      unresolved phylogenies.

PMID- 11252566
TI  - Peering ahead (cautiously).

PMID- 11252565
TI  - The epitome of hand waving? Larval feeding and hypotheses of metazoan phylogeny.
AB  - The homology of larval forms, and particularly their feeding methods, has been a
      major element in some recent discussions about animal phylogeny. "Downstream
      feeding" is one of two main larval-feeding modes and is usually equated to an
      opposed-band system with ciliary bands called the prototroch and metatroch.
      Feeding in larvae is reviewed here and the homology hypothesis of downstream
      larval feeding is expanded, encompassing any feeding involving the prototroch. It
      is often argued that the presence of planktotrophic larvae using downstream
      feeding is plesiomorphic among spiralian animals, and that there is a bias in
      transformations, such that feeding larvae tend to be lost rather than gained.
      These hypotheses are assessed using cladistic parsimony methodology, in relation
      to Spiralia, Trochozoa, and with particular reference to polychaete annelids.
      Methods adopted for the possibility of a bias in transformations toward loss of
      downstream larval feeding include: expanded primary homology arguments, character
      reconstructions favoring reversals, and polymorphic terminals coded as having
      downstream larval feeding. Nevertheless, all analyses show that downstream larval
      feeding appears to have evolved multiple times from a lecithotrophic condition.
      The results support a conclusion that the prototroch was primarily locomotory,
      and has become associated with feeding a number of times. Hypotheses of metazoan
      phylogeny predicated on the assumption that downstream-feeding larvae are
      plesiomorphic are re-assessed.

PMID- 11252567
TI  - The origin of metamorphosis.

PMID- 11252568
TI  - Ancestors and variants: tales from the cryptic.
AB  - Those who work at the interface of development and evolution are united by the
      conviction that developmental comparisons can shed light on both the evolution of
      specific morphologies and the macroevolutionary process itself. In practice,
      however, the field comprises a diversity of approaches. As the field grows and
      practitioners attempt to digest a growing mountain of comparative data, the
      various approaches of "Evo Devo" have themselves evolved. A meeting organized by
      the authors and held at the University of Chicago in the Spring of 1999
      illustrated some of these changes. This review will draw on its content to
      discuss recent developments in two areas: the reconstruction of common ancestors
      and the developmental basis of evolutionary change.

PMID- 11252569
TI  - Novel gene expression patterns in hybrid embryos between species with different
      modes of development.
AB  - Cross-species hybrids between eggs of the direct-developing sea urchin,
      Heliocidaris erythrogramma, and sperm from its congeneric indirect-developing
      species, Heliocidaris tuberculata, show restoration of features of the paternal
      feeding pluteus larva, including the gut, and pluteus spicular skeleton. Unlike
      other reported sea urchin cross-species hybrids, Heliocidaris hybrids express
      genes derived from both maternal and paternal species at high levels. Ectodermal
      cell types, which differ radically between the two parental species, are of
      intermediate form in the hybrids. Gene expression patterns in hybrid embryo
      tissues represent a number of combinations of parental gene expression patterns:
      genes that are not expressed in one paternal species, but are expressed in
      hybrids as in the expressing parent; genes that show additive expression patterns
      plus novel sites of expression; a gene that is misexpressed in the hybrids; and
      genes expressed identically in both parents and in hybrids. The results indicate
      that both conserved and novel gene regulatory interactions are present. Only one
      gene, CyIII actin, has lost cell-type-specific regulation in the hybrids. Hybrids
      thus reveal that disparate parental genomes, each with its own genic regulatory
      system, can produce in combination a novel gene expression entity with a unique
      ontogeny. This outcome may derive from conserved gene regulatory regions in
      downstream genes of both parental species responding in conserved ways to higher
      level regulators that determine modular gene expression territories.

PMID- 11252571
TI  - The significance of moulting in Ecdysozoan evolution.
AB  - Three major bilaterian clades first appear in the Early Cambrian fossil record:
      Deuterostomia, Lophotrochozoa, and Ecdysozoa. The taxa placed in Ecdysozoa are
      characterized by a moulting habit, unknown in the other major clades. The origin
      and consequences of moulting are of fundamental importance to the history of the
      ecdysozoan clade, chiefly because moulting precludes motile ectodermal cilia.
      Moulting may have originated as an adaptation to permit the enlargement, during
      growth, of secreted cuticular spines, flanges, and other structures used as
      ancillary locomotory devices. A combination of phylogenetic and fossil evidence
      suggests that the early members of these clades were small vermiform
      paracoelomates that likely lacked indirect-developing planktotrophic larvae.
      Thus, the evolution of planktotrophic larvae may have been independently achieved
      at least three times within Bilateria. The nonmoulting clades evolved larvae that
      swim and feed via ciliated tufts and bands, presumably intercalating these forms
      within their early developmental systems. Within Ecdysozoa, feeding larvae lacked
      ciliary feeding tracts and evolved by modification of early instars, employing
      limbs or setae to generate feeding currents. The setting aside during larval life
      of cells that give rise to adult features is probably an adaptation associated
      with metamorphosis.

PMID- 11252570
TI  - Maxillopedia is the Tribolium ortholog of proboscipedia.
AB  - Null mutations in the Drosophila melanogaster homeotic gene proboscipedia (pb)
      cause transformation of the adult labial palps to legs. The similar phenotype
      produced by mutations in the Tribolium castaneum homeotic complex (HOMC) gene
      maxillopedia (mxp) has led to suggestions that the two genes may be orthologous.
      We have cloned the Tribolium ortholog of pb, which predicts a protein with a
      homeodomain identical to that of Drosophila Pb. The two proteins also share
      several additional regions of identity, including an N-box, a motif unique to Pb
      orthologs. We have identified a frameshift mutation within Tribolium pb
      associated with an mxp null mutation, demonstrating that Tribolium pb corresponds
      to the mxp genetic locus. Thus, we will refer to the cloned gene as mxp. In
      addition, we have begun to construct a molecular map of the Tribolium HOMC. Two
      overlapping BAC clones which span the mxp locus also include the Tribolium labial
      ortholog (Tclabial) and part of Tczerknullt, indicating that the order of these
      genes in the HOMC is conserved between Drosophila and Tribolium.

PMID- 11252572
TI  - Limbs and tail as evolutionarily diverging duplicates of the main body axis.
AB  - Contrasting hypotheses have been proposed to explain the pervasive parallels in
      the patterning of arthropod and vertebrate appendages. These hypotheses either
      call for a common ancestor already provided with patterned appendages or body
      outgrowths, or for the recruitment in limb patterning of single genes or genetic
      cassettes originally used for purposes other than axis patterning. I suggest
      instead that body appendages such as arthropod and vertebrate limbs and chordate
      tails are evolutionarily divergent duplicates (paramorphs) of the main body axis,
      that is, its duplicates, albeit devoid of endodermal component. Thus, vertebrate
      limbs and arthropod limbs are not historical homologs, but homoplastic features
      only transitively related to real historical homologs. Thus, the main body axis
      and the axis of the appendages have distinct but not independent evolutionary
      histories and may be involved in processes of homeotic co-option producing
      effects of morphological assimilation. For instance, chordate segmentation may
      have originated in the posterior appendage (tail) and subsequently extended to
      the trunk.

PMID- 11252573
TI  - From phenotype to genotype.
AB  - Advances in the field of genomics have made it possible to decipher the genetic
      and transcriptional changes that underlie differences among organisms. Here we
      discuss the merits and drawbacks of these strategies as they relate to
      evolutionary biology. We suggest that the molecular basis of natural variation
      can best be interpreted via the intersection of genomic and transcriptome
      approaches. We outline how this might be accomplished in practice and assemble
      the components of a method to comprehend the evolutionary interplay between
      genotype and phenotype.

PMID- 11252574
TI  - [Postoperative pain therapy in pediatrics. Results of a representative survey in
      Germany].
AB  - The last survey addressing postoperative pain management in Germany was published
      in 1987, special data concerning postoperative pain management in pediatric
      patients had not been presented previously. The goal of this survey is to present
      the standard of postoperative pain management in pediatric patients in Germany. A
      detailed questionnaire was mailed to all German anaesthesia departments and
      interdisciplinary intensive care units (n = 1,500) to determine the current
      management of postoperative pain management in pediatric patients. After eight
      weeks, 42.6% of the survey had been returned. Rectally administered acetaminophen
      is the standard drug regimen for postoperative analgesia in children. Compared to
      previous surveys, the use of opioids has increased in popularity. The routine use
      of non-steroid antiinflammatory drugs (NSAIDs) and spasmolytics as well as the
      application of regional anaesthesia techniques is uncommon in pediatric
      postoperative pain management. Compared to other European countries, patient- or
      parent-controlled analgesia is more popular in Germany. Despite modern concepts
      of organization and a great variety of drugs available today, 71.1% of the
      responding anesthesiologists in this survey still believe that pediatric
      postoperative pain management needs to be improved.

PMID- 11252575
TI  - [Intraoperative diagnosis of pheochromocytoma preoperative symptoms in a case of
      Recklinghausen's disease].
AB  - Phaechromocytoma is a rare catecholamine secreting tumor, which occasionally
      presents as a life threatening crisis in association with surgery and anesthesia.
      We report a 58-year-old women with known Recklinghausen's disease who was
      admitted for elective resection of a pancreas tail cystadenoma. A
      cystadenocarcinoma was taken into account differential diagnostically. No
      clinical symtoms or signs pointing to a hormone active tumor were found
      preoperatively. After opening of the abdomen and palpation of the tumor, a
      hypertensive crisis occurred accompanied by considerable tachycardia, leading to
      the tentative diagnosis of a phaeochromocytoma in connection to the known
      phacomatosis. The hypertensive crisis was treated with nitroglycerin and esmolol.
      The putative tumor of the pancreas represented itself as an adrenal tumor without
      relationship to the pancreas. Following ligature of the suprarenal vein,
      antihypertensive therapy could be finished. For stabilization of blood pressure a
      noradrenaline application was necessary in descending dosage over a period of two
      days. The further postoperative course was without complications. The results of
      the urine catecholamine measurements and histological examinations confirmed the
      intraoperative diagnosis. An unidentified phaeochromocytoma is a vital threat for
      patients during surgery and anesthesia. Phaeochromocytomas are observed in
      patients suffering from Recklinghausen's disease (and other phacomatoses) in an
      above average incidence. Therefore, such a tumor should be excluded in these
      patients before elective surgery even if the patient does not show symptoms
      (asymptomatic phaeochromocytomas occur). The determination of catecholamines in
      24 hour urine collections is an easy and specific diagnostic procedure and should
      be used in patients suffering from phacomatoses before elective surgery.

PMID- 11252576
TI  - [Endotracheal intubation of patients with Pierre-Robin sequence. Successful use
      of video intubation laryngoscope].
AB  - Patients with Pierre Robin sequence are a classic model for patients with a
      difficult airway. In these patients tracheal intubation may be facilitated using
      the lateral approach. In a 3-day-old newborn with Pierre Robin sequence,
      scheduled for anaesthesia to take a mould of the cleft palate, we used a video
      intubation laryngoscope to give a video-display of the lateral approach
      intubation technique to the junior colleagues. The video-laryngoscopic view
      allowed detailed demonstration of the intubation procedure to all persons
      present. In addition, video-transmission of the laryngoscope picture enabled the
      attendant anaesthetist to quickly recognise the need for suctioning the
      hypopharynx and to coordinate the direction and extent of laryngeal pressure
      according the video-laryngoscopic findings. Of special value for the
      intuboscopist was the improved view of the cords provided by the video-display
      compared with direct laryngoscopy. This facilitated a non-traumatic insertion of
      the tube into the trachea and allowed reliable confirmation of the intubation
      depth by the tube marking between the vocal cords.

PMID- 11252577
TI  - [Computer simulation and pharmacoeconomics. Computer simulation as an aid for the
      analysis of operating room efficiency: an example].
AB  - In this study we compared operating room (OR) efficiency of total intravenous
      anaesthesia (TIVA) with remifentanil and propofol and balanced anaesthesia (BAL)
      with fentanyl and isoflurane in cataract surgery using computersimulation. We
      simulated patient flow for one OR and for three ORs. Time intervals of patient
      flow were randomly generated from the results of a prospective, randomized trial.
      Both for one and for three ORs, the postanaesthesia care unit (PACU) finished
      earlier and one additional case per OR and per day could be performed when TIVA
      was used for the procedures. Overtime in the PACU was less after TIVA. With a
      workload of 13 or 15 operations per day in three ORs, monitoring equipment for an
      additional patient in the PACU was required when BAL was used. TIVA with
      remifentanil and propofol was associated with more OR efficiency than balanced
      anaesthesia with fentanyl and isoflurane when given for cataract surgery.

PMID- 11252578
TI  - [Neuromuscular monitoring].

PMID- 11252579
TI  - [Perioperative anemia--tolerance or therapy?].

PMID- 11252580
TI  - [Perioperative anemia].
AB  - Anemia is a frequent finding, particularly in the elderly population, and usually
      indicative of a serious disease. The main causes of preoperative anemia are acute
      or chronic hemorrhage, iron deficiency, renal insufficiency, inflammatory and
      neoplastic diseases. A preexisting mild anemia may be enhanced or unmasked by
      surgically induced bleeding or repeated diagnostic phlebotomies, and by a
      postoperative erythropoietic dysfunction caused by the surgical trauma,
      irrespective of any hemorrhage. Low hemoglobin values are associated with a
      distinct increase of mortality and morbidity, both in the normal population and
      perioperatively and in the critically ill patients. The anemia-associated risk is
      exacerbated by preexisting cardiovascular disease, important intraoperative blood
      loss and advanced age. In contradiction to established therapeutical concepts,
      the administration of allogeneic blood beyond hemoglobin levels of 8-10 g/dl has
      not been found to decrease perioperative or intensive care morbidity or
      mortality. Rather, in addition to the inherent long-term risks of transfusions, a
      liberal transfusion strategy seems to increase the incidence of postoperative
      complications. Thus, current transfusion guidelines tend to be interpreted in an
      increasingly restrictive manner. Depending on the urgency of the clinical
      situation, the primary goal should be to diagnose and treat the underlying
      disease, rather than to focus on the symptom anemia. Time permitting, the
      patient's cardiovascular and pulmonary status should be optimized preoperatively.
      Furthermore, iron should be substituted to treat and prevent deficiency.
      Recombinant human erythropoietin has successfully been used to treat anemia of
      chronic renal failure and chronic disease, as well as in the perioperative and
      intensive care setting, and to support the efficiency of autologous programs.

PMID- 11252581
TI  - [Cisatracurium in coronary bypass operations--a comparison with pancuronium.
      Hemodynamic and neuromuscular effects in patients under chronic beta blocker
      treatment].
AB  - OBJECTIVE: The aim of the study was to compare haemodynamic and neuromuscular
      effects of cisatracurium and pancuronium in patients undergoing coronary artery
      bypass grafting (ASA III, good or moderately impaired LV function) who were
      chronically medicated with beta-adrenergic blocking agents. METHODS: 60 Patients
      were randomly assigned in a double-blind fashion to receive
      sufentanil/midazolam/etomidate and either pancuronium (2xED95, group P) or
      cisatracurium (2xED95, group C2 and 4xED95, group C4). Haemodynamic variables
      were measured using arterial and pulmonary arterial catheters, neuromuscular
      transmission was measured using electromyography. RESULTS: The heart rate was
      significantly lower in group C2 (50.2 +/- 6.8 bpm) and in group C4 (54.3 +/- 11
      bpm) than in the pancuronium group (62.4 +/- 13.2 bpm) 3 min after induction of
      anaesthesia and until 60 min after induction. None of the other haemodynamic
      parameters showed any difference between groups. Onset time was 5.22 +/- 3.43 min
      in group P, 6.42 +/- 2.1 min in group C2 and 2.92 +/- 1.2 min in group C4.
      CONCLUSION: Under high-dose opioid induction, bradycardia must be considered if
      cisatracurium is administered to cardiac surgery patients.

PMID- 11252582
TI  - [Ultrasonography and peridural anesthesia. Technical possibilities and
      limitations of ultrasonic examination of the epidural space].
AB  - Epidural anaesthesia (EA) is the most important analgesia technique in obstetrics
      for delivery. In pregnancy, hormonal adjustments lead to an alteration of tissue
      consistency, which often causes an early, untimely loss of resistance. Apart from
      mere inspection and palpation, no useful diagnostic method prior to EA
      performance has been established yet. In this prospective study, we examined 100
      pregnant women, who had been admitted for childbirth and were undergoing epidural
      block (level L3-L4) for delivery. Sonotopography of the lumbar epidural
      structures was performed directly before epidural puncture and childbirth. We
      evaluated the visibility of all anatomical structures and compared all distances
      measured by ultrasonography and during puncture. The correlation between
      distances measured by ultrasound and by puncture needle was high (r2 = 0.79). No
      obvious dependency was found between ultrasonic and puncture angle (r2 = 0.19).
      The temporal distance from ultrasonic examination and puncture causes unavoidable
      differences: each deviation between ultrasound and puncture conditions causes a
      modification of the puncture depth. The patient acceptance of the procedure was
      very good. Ultrasonography offers the possibility to determine site and direction
      of epidural puncture and distance of the epidural space to the skin even before
      the puncture attempt. The ultrasound controlled EA for delivery can easily be
      inserted into the clinical routine. Ultrasonography can fill an important
      diagnostic gap in regional anaesthesia.

PMID- 11252583
TI  - Review times in statistical journals: tilting at windmills?
AB  - Using limited data, I argue that the review times in statistics are far too long
      for the field to keep pace with the rapidly changing environment in science. I
      note that statisticians do not appear to believe in statistics because data on
      the review process are not widely available to members of the profession. I
      suggest a few changes that could be made to speed up the review process, although
      it would appear that a change in our culture is required before the problem will
      be solved.

PMID- 11252584
TI  - Methods for conducting sensitivity analysis of trials with potentially
      nonignorable competing causes of censoring.
AB  - We consider inference for the treatment-arm mean difference of an outcome that
      would have been measured at the end of a randomized follow-up study if, during
      the course of the study, patients had not initiated a nonrandomized therapy or
      dropped out. We argue that the treatment-arm mean difference is not identified
      unless unverifiable assumptions are made. We describe identifying assumptions
      that are tantamount to postulating relationships between the components of a
      pattern-mixture model but that can also be interpreted as imposing restrictions
      on the cause-specific censoring probabilities of a selection model. We then argue
      that, although sufficient for identification, these assumptions are insufficient
      for inference due to the curse of dimensionality. We propose reducing
      dimensionality by specifying semiparametric cause-specific selection models.
      These models are useful for conducting a sensitivity analysis to examine how
      inference for the treatment-arm mean difference changes as one varies the
      magnitude of the cause-specific selection bias over a plausible range. We provide
      methodology for conducting such sensitivity analysis and illustrate our methods
      with an analysis of data from the AIDS Clinical Trial Group (ACTG) study 002.

PMID- 11252585
TI  - A solution to the problem of monotone likelihood in Cox regression.
AB  - The phenomenon of monotone likelihood is observed in the fitting process of a Cox
      model if the likelihood converges to a finite value while at least one parameter
      estimate diverges to +/- infinity. Monotone likelihood primarily occurs in small
      samples with substantial censoring of survival times and several highly
      predictive covariates. Previous options to deal with monotone likelihood have
      been unsatisfactory. The solution we suggest is an adaptation of a procedure by
      Firth (1993, Biometrika 80, 27-38) originally developed to reduce the bias of
      maximum likelihood estimates. This procedure produces finite parameter estimates
      by means of penalized maximum likelihood estimation. Corresponding Wald-type
      tests and confidence intervals are available, but it is shown that penalized
      likelihood ratio tests and profile penalized likelihood confidence intervals are
      often preferable. An empirical study of the suggested procedures confirms
      satisfactory performance of both estimation and inference. The advantage of the
      procedure over previous options of analysis is finally exemplified in the
      analysis of a breast cancer study.

PMID- 11252586
TI  - Akaike's information criterion in generalized estimating equations.
AB  - Correlated response data are common in biomedical studies. Regression analysis
      based on the generalized estimating equations (GEE) is an increasingly important
      method for such data. However, there seem to be few model-selection criteria
      available in GEE. The well-known Akaike Information Criterion (AIC) cannot be
      directly applied since AIC is based on maximum likelihood estimation while GEE is
      nonlikelihood based. We propose a modification to AIC, where the likelihood is
      replaced by the quasi-likelihood and a proper adjustment is made for the penalty
      term. Its performance is investigated through simulation studies. For
      illustration, the method is applied to a real data set.

PMID- 11252587
TI  - A covariance estimator for GEE with improved small-sample properties.
AB  - In this paper, we propose an alternative covariance estimator to the robust
      covariance estimator of generalized estimating equations (GEE). Hypothesis tests
      using the robust covariance estimator can have inflated size when the number of
      independent clusters is small. Resampling methods, such as the jackknife and
      bootstrap, have been suggested for covariance estimation when the number of
      clusters is small. A drawback of the resampling methods when the response is
      binary is that the methods can break down when the number of subjects is small
      due to zero or near-zero cell counts caused by resampling. We propose a bias
      corrected covariance estimator that avoids this problem. In a small simulation
      study, we compare the bias-corrected covariance estimator to the robust and
      jackknife covariance estimators for binary responses for situations involving 10
      40 subjects with equal and unequal cluster sizes of 16-64 observations. The bias
      corrected covariance estimator gave tests with sizes close to the nominal level
      even when the number of subjects was 10 and cluster sizes were unequal, whereas
      the robust and jackknife covariance estimators gave tests with sizes that could
      be 2-3 times the nominal level. The methods are illustrated using data from a
      randomized clinical trial on treatment for bone loss in subjects with periodontal
      disease.

PMID- 11252588
TI  - Bayesian inference on protective antibody levels using case-control data.
AB  - In the study of immune responses to infectious pathogens, the minimum protective
      antibody concentration (MPAC) is a quantity of great interest. We use case
      control data to estimate the posterior distribution of the conditional risk of
      disease given a lower bound on antibody concentration in an at-risk subject. The
      concentration bound beyond which there is high credibility that infection risk is
      zero or nearly so is a candidate for the MPAC. A very simple Gibbs sampling
      procedure that permits inference on the risk of disease given antibody level is
      presented. In problems involving small numbers of patients, the procedure is
      shown to have favorable accuracy and robustness to choice/misspecification of
      priors. Frequentist evaluation indicates good coverage probabilities of
      credibility intervals for antibody-dependent risk, and rules for estimation of
      the MPAC are illustrated with epidemiological data.

PMID- 11252589
TI  - Bayesian partitioning for estimating disease risk.
AB  - This paper presents a Bayesian nonlinear approach for the analysis of spatial
      count data. It extends the Bayesian partition methodology of Holmes, Denison, and
      Mallick (1999, Bayesian partitioning for classification and regression, Technical
      Report, Imperial College, London) to handle data that involve counts. A
      demonstration involving incidence rates of leukemia in New York state is used to
      highlight the methodology. The model allows us to make probability statements on
      the incidence rates around point sources without making any parametric
      assumptions about the nature of the influence between the sources and the
      surrounding location.

PMID- 11252590
TI  - Bias in estimating association parameters for longitudinal binary responses with
      drop-outs.
AB  - This paper considers the impact of bias in the estimation of the association
      parameters for longitudinal binary responses when there are drop-outs. A number
      of different estimating equation approaches are considered for the case where
      drop-out cannot be assumed to be a completely random process. In particular,
      standard generalized estimating equations (GEE), GEE based on conditional
      residuals, GEE based on multivariate normal estimating equations for the
      covariance matrix, and second-order estimating equations (GEE2) are examined.
      These different GEE estimators are compared in terms of finite sample and
      asymptotic bias under a variety of drop-out processes. Finally, the relationship
      between bias in the estimation of the association parameters and bias in the
      estimation of the mean parameters is explored.

PMID- 11252592
TI  - Bayesian approaches to modeling the conditional dependence between multiple
      diagnostic tests.
AB  - Many analyses of results from multiple diagnostic tests assume the tests are
      statistically independent conditional on the true disease status of the subject.
      This assumption may be violated in practice, especially in situations where none
      of the tests is a perfectly accurate gold standard. Classical inference for
      models accounting for the conditional dependence between tests requires that
      results from at least four different tests be used in order to obtain an
      identifiable solution, but it is not always feasible to have results from this
      many tests. We use a Bayesian approach to draw inferences about the disease
      prevalence and test properties while adjusting for the possibility of conditional
      dependence between tests, particularly when we have only two tests. We propose
      both fixed and random effects models. Since with fewer than four tests the
      problem is nonidentifiable, the posterior distributions are strongly dependent on
      the prior information about the test properties and the disease prevalence, even
      with large sample sizes. If the degree of correlation between the tests is known
      a priori with high precision, then our methods adjust for the dependence between
      the tests. Otherwise, our methods provide adjusted inferences that incorporate
      all of the uncertainty inherent in the problem, typically resulting in wider
      interval estimates. We illustrate our methods using data from a study on the
      prevalence of Strongyloides infection among Cambodian refugees to Canada.

PMID- 11252591
TI  - Bayesian semiparametric analysis of developmental toxicology data.
AB  - Modeling of developmental toxicity studies often requires simple parametric
      analyses of the dose-response relationship between exposure and probability of a
      birth defect but poses challenges because of nonstandard distributions of birth
      defects for a fixed level of exposure. This article is motivated by two such
      experiments in which the distribution of the outcome variable is challenging to
      both the standard logistic model with binomial response and its parametric
      multistage elaborations. We approach our analysis using a Bayesian semiparametric
      model that we tailored specifically to developmental toxicology studies. It
      combines parametric dose-response relationships with a flexible nonparametric
      specification of the distribution of the response, obtained via a product of
      Dirichlet process mixtures approach (PDPM). Our formulation achieves three goals:
      (1) the distribution of the response is modeled in a general way, (2) the degree
      to which the distribution of the response adapts nonparametrically to the
      observations is driven by the data, and (3) the marginal posterior distribution
      of the parameters of interest is available in closed form. The logistic
      regression model, as well as many of its extensions such as the beta-binomial
      model and finite mixture models, are special cases. In the context of the two
      motivating examples and a simulated example, we provide model comparisons,
      illustrate overdispersion diagnostics that can assist model specification, show
      how to derive posterior distributions of the effective dose parameters and
      predictive distributions of response, and discuss the sensitivity of the results
      to the choice of the prior distribution.

PMID- 11252594
TI  - On sample size and inference for two-stage adaptive designs.
AB  - Proschan and Hunsberger (1995, Biometrics 51, 1315-1324) proposed a two-stage
      adaptive design that maintains the Type I error rate. For practical applications,
      a two-stage adaptive design is also required to achieve a desired statistical
      power while limiting the maximum overall sample size. In our proposal, a two
      stage adaptive design is comprised of a main stage and an extension stage, where
      the main stage has sufficient power to reject the null under the anticipated
      effect size and the extension stage allows increasing the sample size in case the
      true effect size is smaller than anticipated. For statistical inference, methods
      for obtaining the overall adjusted p-value, point estimate and confidence
      intervals are developed. An exact two-stage test procedure is also outlined for
      robust inference.

PMID- 11252593
TI  - Optimal designs for evaluating a series of treatments.
AB  - Several articles in this journal have studied optimal designs for testing a
      series of treatments to identify promising ones for further study. These designs
      formulate testing as an ongoing process until a promising treatment is
      identified. This formulation is considered to be more realistic but substantially
      increases the computational complexity. In this article, we show that these new
      designs, which control the error rates for a series of treatments, can be
      reformulated as conventional designs that control the error rates for each
      individual treatment. This reformulation leads to a more meaningful
      interpretation of the error rates and hence easier specification of the error
      rates in practice. The reformulation also allows us to use conventional designs
      from published tables or standard computer programs to design trials for a series
      of treatments. We illustrate these using a study in soft tissue sarcoma.

PMID- 11252596
TI  - Estimation of population attributable fractions from fitted incidence ratios and
      exposure survey data, with an application to electromagnetic fields and childhood
      leukemia.
AB  - Standard presentations of epidemiological results focus on incidence-ratio
      estimates derived from regression models fit to specialized study data. These
      data are often highly nonrepresentative of populations for which public-health
      impacts must be evaluated. Basic methods are provided for interval estimation of
      attributable fractions from model-based incidence-ratio estimates combined with
      independent survey estimates of the exposure distribution in the target
      population of interest. These methods are illustrated in estimation of the
      potential impact of magnetic-field exposures on childhood leukemia in the United
      States, based on pooled data from 11 case-control studies and a U.S. sample
      survey of magnetic-field exposures.

PMID- 11252595
TI  - Adjusting for regression effect in uncontrolled studies.
AB  - When clinical studies require enrolled patients to have abnormal assays, the
      natural tendency of repeat measurements to regress toward the mean can lead to a
      false assessment of effectiveness of therapy. We propose a method to more
      accurately estimate the true effect of therapy by adjusting for a component of
      improvement that can be attributed to regression effect. The model we use allows
      for a combination of additive and/or multiplicative effects of the therapy.

PMID- 11252597
TI  - Modeling diurnal variation of marine populations.
AB  - A number of marine populations exhibit diurnal variations in their behavioral
      pattern, and this phenomenon has been studied by several authors looking at a
      variety of species. But to our knowledge, fully adequate statistical tools have
      not been used in a comprehensive and systematic way. It is the goal of this
      article to bring forward relevant statistical techniques and to demonstrate how
      they can be used. Both parametric and nonparametric methods are employed, and we
      concentrate on such basic statistical issues as testing for the presence of
      diurnal variations using a nonparametric test and on estimating and testing the
      shape of diurnal oscillations. We indicate how this can be used to examine the
      effect of light on diurnal behavior. Our methods are illustrated using data from
      bottom trawl catches of cod (Gadus morhua) collected during winter surveys in the
      Barents Sea in the period 1985-1999.

PMID- 11252598
TI  - Detecting interaction between random region and fixed age effects in disease
      mapping.
AB  - The purpose of this article is to draw attention to the possible need for
      inclusion of interaction effects between regions and age groups in mapping
      studies. We propose a simple model for including such an interaction in order to
      develop a test for its significance. The assumption of an absence of such
      interaction effects is a helpful simplifying one. The measure of relative risk
      related to a particular region becomes easily and neatly summarized. Indeed, such
      a test seems warranted because it is anticipated that the simple model, which
      ignores such interaction, as is in common use, may at times be adequate. The test
      proposed is a score test and hence only requires fitting the simpler model. We
      illustrate our approaches using mortality data from British Columbia, Canada,
      over the 5-year period 1985-1989. For this data, the interaction effect between
      age groups and regions is quite large and significant.

PMID- 11252599
TI  - Combining datasets to predict the effects of regulation of environmental lead
      exposure in housing stock.
AB  - A model for children's blood lead concentrations as a function of environmental
      lead exposures was developed by combining two nationally representative sources
      of data that characterize the marginal distributions of blood lead and
      environmental lead with a third regional dataset that contains joint measures of
      blood lead and environmental lead. The complicating factor addressed in this
      article was the fact that methods for assessing environmental lead were different
      in the national and regional datasets. Relying on an assumption of
      transportability (that although the marginal distributions of blood lead and
      environmental lead may be different between the regional dataset and the nation
      as a whole, the joint relationship between blood lead and environmental lead is
      the same), the model makes use of a latent variable approach to estimate the
      joint distribution of blood lead and environmental lead nationwide.

PMID- 11252600
TI  - On the use of the variogram in checking for independence in spatial data.
AB  - The variogram is a standard tool in the analysis of spatial data, and its shape
      provides useful information on the form of spatial correlation that may be
      present. However, it is also useful to be able to assess the evidence for the
      presence of any spatial correlation. A method of doing this, based on an
      assessment of whether the true function underlying the variogram is constant, is
      proposed. Nonparametric smoothing of the squared differences of the observed
      variables, on a suitably transformed scale, is used to estimate variogram shape.
      A statistic based on a ratio of quadratic forms is proposed and the test is
      constructed by investigating the distributional properties of this statistic
      under the assumption of an independent Gaussian process. The power of the test is
      investigated. Reference bands are proposed as a graphical follow-up. An example
      is discussed.

PMID- 11252601
TI  - A score test for testing a zero-inflated Poisson regression model against zero
      inflated negative binomial alternatives.
AB  - Count data often show a higher incidence of zero counts than would be expected if
      the data were Poisson distributed. Zero-inflated Poisson regression models are a
      useful class of models for such data, but parameter estimates may be seriously
      biased if the nonzero counts are overdispersed in relation to the Poisson
      distribution. We therefore provide a score test for testing zero-inflated Poisson
      regression models against zero-inflated negative binomial alternatives.

PMID- 11252602
TI  - Multiple imputation for multivariate data with missing and below-threshold
      measurements: time-series concentrations of pollutants in the Arctic.
AB  - Many chemical and environmental data sets are complicated by the existence of
      fully missing values or censored values known to lie below detection thresholds.
      For example, week-long samples of airborne particulate matter were obtained at
      Alert, NWT, Canada, between 1980 and 1991, where some of the concentrations of 24
      particulate constituents were coarsened in the sense of being either fully
      missing or below detection limits. To facilitate scientific analysis, it is
      appealing to create complete data by filling in missing values so that standard
      complete-data methods can be applied. We briefly review commonly used strategies
      for handling missing values and focus on the multiple-imputation approach, which
      generally leads to valid inferences when faced with missing data. Three
      statistical models are developed for multiply imputing the missing values of
      airborne particulate matter. We expect that these models are useful for creating
      multiple imputations in a variety of incomplete multivariate time series data
      sets.

PMID- 11252603
TI  - The K-function for nearly regular point processes.
AB  - We propose modeling a nearly regular point pattern by a generalized Neyman-Scott
      process in which the offspring are Gaussian perturbations from a regular mean
      configuration. The mean configuration of interest is an equilateral grid, but our
      results can be used for any stationary regular grid. The case of uniformly
      distributed points is first studied as a benchmark. By considering the square of
      the interpoint distances, we can evaluate the first two moments of the K
      function. These results can be used for parameter estimation, and simulations are
      used to both verify the theory and to assess the accuracy of the estimators. The
      methodology is applied to an investigation of regularity in plumes observed from
      swimming microorganisms.

PMID- 11252604
TI  - An evaluation of semiautomatic approaches to contour segmentation applied to
      fungal hyphae.
AB  - Semiautomatic image analysis techniques are particularly useful in biological
      applications, which commonly generate very complex images, and offer considerable
      flexibility. However, systematic study of such methods is lacking; most research
      develops fully automatic algorithms. This paper describes a study to evaluate
      several different semiautomatic or computer-assisted approaches to contour
      segmentation within the context of segmenting degraded images of fungal hyphae.
      Four different types of contour segmentation method, with varying degrees and
      types of user input, are outlined and applied to hyphal images. The methods are
      evaluated both quantitatively and qualitatively by comparing results obtained by
      several test subjects segmenting simulated images qualitatively similar to the
      hyphal images of interest. An active contour model approach, using control
      points, emerges as the method to be preferred to three more traditional
      approaches. Feedback from the image provider indicates that any of the methods
      described have something useful to offer for segmentation of hyphae.

PMID- 11252605
TI  - Minimizing model fitting objectives that contain spurious local minima by
      bootstrap restarting.
AB  - Objective functions that arise when fitting nonlinear models often contain local
      minima that are of little significance except for their propensity to trap
      minimization algorithms. The standard methods for attempting to deal with this
      problem treat the objective function as fixed and employ stochastic minimization
      approaches in the hope of randomly jumping out of local minima. This article
      suggests a simple trick for performing such minimizations that can be employed in
      conjunction with most conventional nonstochastic fitting methods. The trick is to
      stochastically perturb the objective function by bootstrapping the data to be
      fit. Each bootstrap objective shares the large-scale structure of the original
      objective but has different small-scale structure. Minimizations of bootstrap
      objective functions are alternated with minimizations of the original objective
      function starting from the parameter values with which minimization of the
      previous bootstrap objective terminated. An example is presented, fitting a
      nonlinear population dynamic model to population dynamic data and including a
      comparison of the suggested method with simulated annealing. Convergence
      diagnostics are discussed.

PMID- 11252606
TI  - A marginal likelihood approach for estimating penetrance from kin-cohort designs.
AB  - The kin-cohort design is a promising alternative to traditional cohort or case
      control designs for estimating penetrance of an identified rare autosomal
      mutation. In this design, a suitably selected sample of participants provides
      genotype and detailed family history information on the disease of interest. To
      estimate penetrance of the mutation, we consider a marginal likelihood approach
      that is computationally simple to implement, more flexible than the original
      analytic approach proposed by Wacholder et al. (1998, American Journal of
      Epidemiology 148, 623-629), and more robust than the likelihood approach
      considered by Gail et al. (1999, Genetic Epidemiology 16, 15-39) to presence of
      residual familial correlation. We study the trade-off between robustness and
      efficiency using simulation experiments. The method is illustrated by analysis of
      the data from the Washington Ashkenazi Study.

PMID- 11252607
TI  - Nonparametric mixed effects models for unequally sampled noisy curves.
AB  - We propose a method of analyzing collections of related curves in which the
      individual curves are modeled as spline functions with random coefficients. The
      method is applicable when the individual curves are sampled at variable and
      irregularly spaced points. This produces a low-rank, low-frequency approximation
      to the covariance structure, which can be estimated naturally by the EM
      algorithm. Smooth curves for individual trajectories are constructed as best
      linear unbiased predictor (BLUP) estimates, combining data from that individual
      and the entire collection. This framework leads naturally to methods for
      examining the effects of covariates on the shapes of the curves. We use model
      selection techniques--Akaike information criterion (AIC), Bayesian information
      criterion (BIC), and cross-validation--to select the number of breakpoints for
      the spline approximation. We believe that the methodology we propose provides a
      simple, flexible, and computationally efficient means of functional data
      analysis.

PMID- 11252608
TI  - Likelihood ratio tests for a mixture of two von Mises distributions.
AB  - It is proposed that the orientation of elongate objects, such as bones, may be
      used to identify the flow direction of ancient river deposits. If true, elongate
      objects could be of great value when ancient bedforms such as ripples and dunes
      are not visible. Two sandstone quarries were investigated wherein the paleoflow
      direction was determined from both bedforms and elongate dinosaur bones. A
      mixture of two von Mises distributions captures the observation that elongate
      bones transported under unidirectional flow conditions will align both parallel
      and perpendicular to the flow direction. Likelihood ratio tests for a mixture of
      two von Mises distributions are given. The power of these tests is investigated
      by simulation since the direction of dinosaur bones agrees with the primary
      bedforms if the hypothesis test comparing the dominant mean direction of the
      bones to the paleoflow direction fails to reject. The likelihood ratio test on
      the dominant mean direction has reasonable power. If the two mean directions in
      the mixture distribution are pi apart, a more powerful likelihood ratio test can
      be used. The likelihood ratio test on the hypothesis that the two mean directions
      are exactly pi apart is useful in determining if the assumptions of the more
      powerful test are satisfied.

PMID- 11252609
TI  - Robust two-stage estimation in hierarchical nonlinear models.
AB  - Hierarchical models encompass two sources of variation, namely within and among
      individuals in the population; thus, it is important to identify outliers that
      may arise at each sampling level. A two-stage approach to analyzing nonlinear
      repeated measurements naturally allows parametric modeling of the respective
      variance structure for the intraindividual random errors and interindividual
      random effects. We propose a robust two-stage procedure based on Huber's (1981,
      Robust Statistics) theory of M-estimation to accommodate separately aberrant
      responses within an experimental unit and subjects deviating from the study
      population when the usual assumptions of normality are violated. A toxicology
      study of chronic ozone exposure in rats illustrates the impact of outliers on the
      population inference and hence the advantage of adopting the robust methodology.
      The robust weights generated by the two-stage M-estimation process also serve as
      diagnostics for gauging the relative influence of outliers at each level of the
      hierarchical model. A practical appeal of our proposal is the computational
      simplicity since the estimation algorithm may be implemented using standard
      statistical software with a nonlinear least squares routine and iterative
      capability.

PMID- 11252610
TI  - Combining band recovery data and Pollock's robust design to model temporary and
      permanent emigration.
AB  - Capture-recapture models are widely used to estimate demographic parameters of
      marked populations. Recently, this statistical theory has been extended to
      modeling dispersal of open populations. Multistate models can be used to estimate
      movement probabilities among subdivided populations if multiple sites are
      sampled. Frequently, however, sampling is limited to a single site. Models
      described by Burnham (1993, in Marked Individuals in the Study of Bird
      Populations, 199-213), which combined open population capture-recapture and band
      recovery models, can be used to estimate permanent emigration when sampling is
      limited to a single population. Similarly, Kendall, Nichols, and Hines (1997,
      Ecology 51, 563-578) developed models to estimate temporary emigration under
      Pollock's (1982, Journal of Wildlife Management 46, 757-760) robust design. We
      describe a likelihood-based approach to simultaneously estimate temporary and
      permanent emigration when sampling is limited to a single population. We use a
      sampling design that combines the robust design and recoveries of individuals
      obtained immediately following each sampling period. We present a general form
      for our model where temporary emigration is a first-order Markov process, and we
      discuss more restrictive models. We illustrate these models with analysis of data
      on marked Canvasback ducks. Our analysis indicates that probability of permanent
      emigration for adult female Canvasbacks was 0.193 (SE = 0.082) and that birds
      that were present at the study area in year i - 1 had a higher probability of
      presence in year i than birds that were not present in year i - 1.

PMID- 11252611
TI  - Nonparametric estimation in a cure model with random cure times.
AB  - Acute respiratory distress syndrome (ARDS) is a life-threatening acute condition
      that sometimes follows pneumonia or surgery. Patients who recover and leave the
      hospital are considered to have been cured at the time they leave the hospital.
      These data differ from typical data in which cure is a possibility: death times
      are not observed for patients who are cured and cure times are observed and vary
      among patients. Here we apply a competing risks model to these data and show it
      to be equivalent to a mixture model, the more common approach for cure data.
      Further, we derive an estimator for the variance of the cumulative incidence
      function from the competing risks model, and thus for the cure rate, based on
      elementary calculations. We compare our variance estimator to Gray's (1988,
      Annals of Statistics 16, 1140-1154) estimator, which is based on counting process
      theory. We find our estimator to be slightly more accurate in small samples. We
      apply these results to data from an ARDS clinical trial.

PMID- 11252612
TI  - Catch estimation in the presence of declining catch rate due to gear saturation.
AB  - One strategy for estimating total catch is to employ two separate surveys that
      independently estimate total fishing effort and catch rate with the estimator for
      total catch formed by their product. Survey designs for estimating catch rate
      often involve interviewing the fishermen during their fishing episodes. Such
      roving designs result in incomplete episode data and characteristically have
      employed a model in which the catch rate is assumed to be constant over time.
      This article extends the problem to that of estimating total catch in the
      presence of a declining catch rate due, e.g., to gear saturation. Using a gill
      net fishery as an example, a mean-of-ratios type of estimator for the catch rate
      together with its variance estimator are developed. Their performance is examined
      using simulations, with special attention given to effects of restrictions on the
      roving survey window. Finally, data from a Fraser River gill net fishery are used
      to illustrate the use of the proposed estimator and to compare results with those
      from an estimator based on a constant catch rate.

PMID- 11252613
TI  - Statistical evaluation of the regulatory guidelines for use of furosemide in race
      horses.
AB  - The pharmacokinetic behavior of furosemide concentrations in performance horses
      is of great interest to the equine industry and equine researchers. Specifically,
      such information is useful for the evaluation of the existing guidelines in
      several racing jurisdictions and for the possible development of new guidelines
      for varying time periods after administration. We studied several approaches
      within the framework of nonlinear mixed effects models to increase the accuracy
      of evaluating these guidelines. Theoretical properties of the proposed methods
      were examined and the variances of the resulting estimators compared. Their
      numerical performances were further evaluated through simulations. Finally, we
      applied these methods to a furosemide concentration profile data set and used our
      findings to address certain important practical issues.

PMID- 11252614
TI  - Factor analytic models of clustered multivariate data with informative censoring.
AB  - This article describes a general class of factor analytic models for the analysis
      of clustered multivariate data in the presence of informative missingness. We
      assume that there are distinct sets of cluster-level latent variables related to
      the primary outcomes and to the censoring process, and we account for dependency
      between these latent variables through a hierarchical model. A linear model is
      used to relate covariates and latent variables to the primary outcomes for each
      subunit. A generalized linear model accounts for covariate and latent variable
      effects on the probability of censoring for subunits within each cluster. The
      model accounts for correlation within clusters and within subunits through a
      flexible factor analytic framework that allows multiple latent variables and
      covariate effects on the latent variables. The structure of the model facilitates
      implementation of Markov chain Monte Carlo methods for posterior estimation. Data
      from a spermatotoxicity study are analyzed to illustrate the proposed approach.

PMID- 11252615
TI  - A Bayesian decision approach for sample size determination in phase II trials.
AB  - Stallard (1998, Biometrics 54, 279-294) recently used Bayesian decision theory
      for sample-size determination in phase II trials. His design maximizes the
      expected financial gains in the development of a new treatment. However, it
      results in a very high probability (0.65) of recommending an ineffective
      treatment for phase III testing. On the other hand, the expected gain using his
      design is more than 10 times that of a design that tightly controls the false
      positive error (Thall and Simon, 1994, Biometrics 50, 337-349). Stallard's design
      maximizes the expected gain per phase II trial, but it does not maximize the rate
      of gain or total gain for a fixed length of time because the rate of gain depends
      on the proportion of treatments forwarding to the phase III study. We suggest
      maximizing the rate of gain, and the resulting optimal one-stage design becomes
      twice as efficient as Stallard's one-stage design. Furthermore, the new design
      has a probability of only 0.12 of passing an ineffective treatment to phase III
      study.

PMID- 11252616
TI  - Maximum likelihood analysis of logistic regression models with incomplete
      covariate data and auxiliary information.
AB  - This article presents a new method for maximum likelihood estimation of logistic
      regression models with incomplete covariate data where auxiliary information is
      available. This auxiliary information is extraneous to the regression model of
      interest but predictive of the covariate with missing data. Ibrahim (1990,
      Journal of the American Statistical Association 85, 765-769) provides a general
      method for estimating generalized linear regression models with missing
      covariates using the EM algorithm that is easily implemented when there is no
      auxiliary data. Vach (1997, Statistics in Medicine 16, 57-72) describes how the
      method can be extended when the outcome and auxiliary data are conditionally
      independent given the covariates in the model. The method allows the
      incorporation of auxiliary data without making the conditional independence
      assumption. We suggest tests of conditional independence and compare the
      performance of several estimators in an example concerning mental health service
      utilization in children. Using an artificial dataset, we compare the performance
      of several estimators when auxiliary data are available.

PMID- 11252617
TI  - Maximum likelihood methods for cure rate models with missing covariates.
AB  - We propose maximum likelihood methods for parameter estimation for a novel class
      of semiparametric survival models with a cure fraction, in which the covariates
      are allowed to be missing. We allow the covariates to be either categorical or
      continuous and specify a parametric distribution for the covariates that is
      written as a sequence of one-dimensional conditional distributions. We propose a
      novel EM algorithm for maximum likelihood estimation and derive standard errors
      by using Louis's formula (Louis, 1982, Journal of the Royal Statistical Society,
      Series B 44, 226-233). Computational techniques using the Monte Carlo EM
      algorithm are discussed and implemented. A real data set involving a melanoma
      cancer clinical trial is examined in detail to demonstrate the methodology.

PMID- 11252618
TI  - Semiparametric maximum likelihood for measurement error model regression.
AB  - This paper presents an EM algorithm for semiparametric likelihood analysis of
      linear, generalized linear, and nonlinear regression models with measurement
      errors in explanatory variables. A structural model is used in which probability
      distributions are specified for (a) the response and (b) the measurement error. A
      distribution is also assumed for the true explanatory variable but is left
      unspecified and is estimated by nonparametric maximum likelihood. For various
      types of extra information about the measurement error distribution, the proposed
      algorithm makes use of available routines that would be appropriate for
      likelihood analysis of (a) and (b) if the true x were available. Simulations
      suggest that the semiparametric maximum likelihood estimator retains a high
      degree of efficiency relative to the structural maximum likelihood estimator
      based on correct distributional assumptions and can outperform maximum likelihood
      based on an incorrect distributional assumption. The approach is illustrated on
      three examples with a variety of structures and types of extra information about
      the measurement error distribution.

PMID- 11252619
TI  - Covariate measurement error adjustment for matched case-control studies.
AB  - We propose a conditional scores procedure for obtaining bias-corrected estimates
      of log odds ratios from matched case-control data in which one or more covariates
      are subject to measurement error. The approach involves conditioning on
      sufficient statistics for the unobservable true covariates that are treated as
      fixed unknown parameters. For the case of Gaussian nondifferential measurement
      error, we derive a set of unbiased score equations that can then be solved to
      estimate the log odds ratio parameters of interest. The procedure successfully
      removes the bias in naive estimates, and standard error estimates are obtained by
      resampling methods. We present an example of the procedure applied to data from a
      matched case-control study of prostate cancer and serum hormone levels, and we
      compare its performance to that of regression calibration procedures.

PMID- 11252620
TI  - Sensitivity analysis for nonrandom dropout: a local influence approach.
AB  - Diggle and Kenward (1994, Applied Statistics 43, 49-93) proposed a selection
      model for continuous longitudinal data subject to nonrandom dropout. It has
      provoked a large debate about the role for such models. The original enthusiasm
      was followed by skepticism about the strong but untestable assumptions on which
      this type of model invariably rests. Since then, the view has emerged that these
      models should ideally be made part of a sensitivity analysis. This paper presents
      a formal and flexible approach to such a sensitivity assessment based on local
      influence (Cook, 1986, Journal of the Royal Statistical Society, Series B 48, 133
      169). The influence of perturbing a missing-at-random dropout model in the
      direction of nonrandom dropout is explored. The method is applied to data from a
      randomized experiment on the inhibition of testosterone production in rats.

PMID- 11252621
TI  - Nonparametric maximum likelihood estimation for competing risks survival data
      subject to interval censoring and truncation.
AB  - We derive the nonparametric maximum likelihood estimate (NPMLE) of the cumulative
      incidence functions for competing risks survival data subject to interval
      censoring and truncation. Since the cumulative incidence function NPMLEs give
      rise to an estimate of the survival distribution which can be undefined over a
      potentially larger set of regions than the NPMLE of the survival function
      obtained ignoring failure type, we consider an alternative pseudolikelihood
      estimator. The methods are then applied to data from a cohort of injecting drug
      users in Thailand susceptible to infection from HIV-1 subtypes B and E.

PMID- 11252623
TI  - Nonparametric models and methods for designs with dependent censored data: part
      I.
AB  - We consider a nonparametric (NP) approach to the analysis of repeated measures
      designs with censored data. Using the NP model of Akritas and Arnold (1994,
      Journal of the American Statistical Association 89, 336-343) for marginal
      distributions, we present test procedures for the NP hypotheses of no main
      effects, no interaction, and no simple effects. This extends the existing NP
      methodology for such designs (Wei and Lachin, 1984, Journal of the American
      Statistical Association 79, 653-661). The procedures do not require any modeling
      assumptions and should be useful in cases where the assumptions of proportional
      hazards or location shift fail to be satisfied. The large-sample distribution of
      the test statistics is based on an i.i.d. representation for Kaplan-Meier
      integrals. The testing procedures apply also to ordinal data and to data with
      ties. Useful small-sample approximations are presented, and their performance is
      examined in a simulation study. Finally, the methodology is illustrated with two
      real life examples, one with censored and one with missing data. It is indicated
      that one of the data sets does not conform to any set of assumptions underlying
      the available methods and also that the present method provides a useful
      additional analysis even when data sets conform to modeling assumptions.

PMID- 11252622
TI  - The evaluation of multiple surrogate endpoints.
AB  - Surrogate endpoints are desirable because they typically result in smaller,
      faster efficacy studies compared with the ones using the clinical endpoints.
      Research on surrogate endpoints has received substantial attention lately, but
      most investigations have focused on the validity of using a single biomarker as a
      surrogate. Our paper studies whether the use of multiple markers can improve
      inferences about a treatment's effects on a clinical endpoint. We propose a joint
      model for a time to clinical event and for repeated measures over time on
      multiple biomarkers that are potential surrogates. This model extends the
      formulation of Xu and Zeger (2001, in press) and Fawcett and Thomas (1996,
      Statistics in Medicine 15, 1663-1685). We propose two complementary measures of
      the relative benefit of multiple surrogates as opposed to a single one. Markov
      chain Monte Carlo is implemented to estimate model parameters. The methodology is
      illustrated with an analysis of data from a schizophrenia clinical trial.

PMID- 11252624
TI  - Multilevel models for survival analysis with random effects.
AB  - A method for modeling survival data with multilevel clustering is described. The
      Cox partial likelihood is incorporated into the generalized linear mixed model
      (GLMM) methodology. Parameter estimation is achieved by maximizing a log
      likelihood analogous to the likelihood associated with the best linear unbiased
      prediction (BLUP) at the initial step of estimation and is extended to obtain
      residual maximum likelihood (REML) estimators of the variance component.
      Estimating equations for a three-level hierarchical survival model are developed
      in detail, and such a model is applied to analyze a set of chronic granulomatous
      disease (CGD) data on recurrent infections as an illustration with both hospital
      and patient effects being considered as random. Only the latter gives a
      significant contribution. A simulation study is carried out to evaluate the
      performance of the REML estimators. Further extension of the estimation procedure
      to models with an arbitrary number of levels is also discussed.

PMID- 11252625
TI  - Glycoconjugate distribution in early human notochord and axial mesenchyme.
AB  - Glycosylation patterns of cells and tissues give insights into spatially and
      temporally regulated developmental processes and can be detected histochemically
      using plant lectins with specific affinities for sugar moieties. The early
      development of the vertebral column in man is a process which has never been
      investigated by lectin histochemistry. Therefore, we studied binding of several
      lectins (AIA, Con A, GSA II, LFA, LTA, PNA, RCA I, SBA, SNA, WGA) in formaldehyde
      fixed sections of the axial mesenchyme of 5 human embryos in Carnegie stages 12
      15. During these developmental stages, an unsegmented mesenchyme covers the
      notochord. Staining patterns did not show striking temporal variations except for
      SBA which stained the cranial axial mesenchyme only in the early stage 12 embryo
      and for PNA, of which the staining intensity in the mesenchyme decreased with
      age. The notochord appeared as a highly glycosylated tissue. Carbohydrates
      detected may correspond to adhesion molecules or to secreted substances like
      proteoglycans or proteins which could play an inductive role, for example, for
      the neural tube. The axial perinotochordal unsegmented mesenchyme showed strong
      PNA binding. Therefore, its function as a PNA-positive "barrier" tissue is
      discussed. The endoderm of the primitive gut showed a lectin-binding pattern that
      was similar to that of the notochord, which may correlate with interactions
      between these tissues during earlier developmental stages.

PMID- 11252627
TI  - A contribution to the fox Ulrich Welsch on the occasion of his 60th birthday.

PMID- 11252626
TI  - N-acetylgalactosamine, N-acetylglucosamine and sialic acid expression in primary
      breast cancers.
AB  - Binding of the lectin from Helix pomatia (HPA), which recognises N
      acetylgalactosamine and N-acetylglucosamine glycans, is a predictor of metastasis
      and poor prognosis in a number of human adenocarcinomas, including breast cancer.
      The glycoproteins to which it binds in these tumours have been only partially
      characterised, and the mechanisms underlying their biosynthesis remain unknown.
      In this study, 111 primary breast cancers were assessed for binding of HPA and
      labelling characteristics were compared directly with those of Dolichos biflorus
      agglutinin and soybean agglutinin, both of which also recognise N
      acetylgalactosamine, Griffonia simplicifolia agglutinin II, which recognises N
      acetylglucosamine, and Limax flavus agglutinin, Sambucus nigra agglutinin and
      Maackia amurensis lectin I, all of which recognise sialic acids. Results indicate
      that the HPA-binding partners expressed by cancer cells are predominantly N
      acetylgalactosamine glycans, but some recognition of N-acetylglucosamine species
      is also likely. There was no evidence to support the hypothesis that
      overexpression of these moieties results from failure in sialylation. Alternative
      mechanisms, for example alterations in levels of activity of appropriate glycosyl
      transferases or disruption in transport and processing mechanisms leading to
      failure of normal chain extension of glycans may be responsible, and these are
      areas that warrant further investigation.

PMID- 11252629
TI  - Neuropeptide Y immunohistochemistry and ultrastructure of developing chromaffin
      tissue in the cloudy dogfish, Scyliorhinus torazame (Chondrichthyes,
      Elasmobranchii).
AB  - Ontogenetic changes in neuropeptide Y-like immunoreactivity (NPY-LI) were studied
      in chromaffin tissue of the cloudy dogfish, Scyliorhinus torazame. In adults and
      post-hatching juveniles, NPY-LI was demonstrated in chromaffin cells, but not in
      ganglion cells and supporting cells. Immunoreactive fibers were also found in the
      axillary body (the major chromaffin tissue) of the adult fish. During the
      embryonic period, NPY-LI was found at first in chromaffin tissue in the 34-mm
      stage. In this stage, cells in the periphery of the tissue were positive for NPY.
      Afterwards, changes were not observed in the topography and relative dominance of
      labelled cells in the tissue. Transmission electron microscopy of chromaffin
      tissue of the 26-mm stage showed an early phase of histogenesis in rudimental
      cell clusters composed of agranular cells and a few granular cells, i.e.
      pheochromoblasts. In the 43-mm stage, differentiation of the chromaffin tissue
      enabled ultrastructural classification of adrenalin-producing cells, noradrenalin
      producing cells, ganglion cells, supporting cells, and unmyelinated nerve fibers.
      These results suggest that in the dogfish the appearance of NPY-LI in the
      developing sympathoadrenal system is related to differentiation of chromaffin
      cells.

PMID- 11252628
TI  - Cell turnover in apocrine metaplasia of the human mammary gland epithelium:
      apoptosis, proliferation, and immunohistochemical detection of Bcl-2, Bax, EGFR,
      and c-erbB2 gene products.
AB  - Apocrine metaplasia is considered to be a benign lesion of human mammary
      epithelium. However, it is not known how apocrine differentiation develops, and
      whether there is a relationship with particular subtypes of mammary carcinoma. In
      order to investigate cell turnover in apocrine metaplasia, apoptosis was detected
      by terminal transferase nick-end-labelling, and Ki-67 was used as proliferation
      marker. Bcl-2, Bax, epidermal growth factor receptor (EGFR), and c-erbB2-encoded
      protein were detected by immunohistochemistry. The proliferative activity was low
      (<1%). Frequency and intraepithelial localization of apoptotic cells resembled
      those of normal mammary epithelium. Bax immunostaining was inconstant and weak,
      and Bcl-2 was not detectable in apocrine metaplasia. Immunoreactivity of the c
      erbB2 gene product was membrane-bound and showed a moderate to strong intensity,
      whereas staining for EGFR was weak and inconsistent. When compared with normal
      breast epithelium, apocrine metaplasia shows a regular cell turnover at a low
      rate, although the expression patterns of regulatory proteins are clearly
      altered. Our data suggest that changes in the expression of Bcl-2 or c-erbB2
      protein do not result in a significant imbalance of apoptosis and proliferation,
      and thus should not be interpreted as indicator for increased risk of neoplastic
      transformation.

PMID- 11252630
TI  - Immunohistochemical detection of simian immunodeficiency virus (SIV) in rectal
      mucosa of experimentally infected rhesus macaques (Macaca mulatta).
AB  - Experimental simian immunodeficiency virus (SIV) infection is the most
      appropriate animal model for human HIV infection. Eight male rhesus monkeys
      (Macaca mulatta) were intravenously or intrarectally infected with
      SIVmac251/MPBMC to comparatively investigate the distribution and spread of the
      virus within the rectum during the course of the disease. SIV-positive cells were
      immunohistochemically detected in rectal biopsies obtained at days 3 and 7 and
      week 2, 4 and 12 postinfection. SIV-expressing cells were detected for the first
      time at one week after experimental infection and were present in the lamina
      propria and lymph follicles. Numbers of positive cells per individual animal
      varied strongly in time, with a more rapid rise in animals with rapid progression
      of the disease. Differences were not observed between intravenous and intrarectal
      infection. Our observations support the significance of the intestinal tract as
      target organ in initial pathogenesis of SIV infection.

PMID- 11252631
TI  - Immunolocalization of the mitogen-activated protein kinase signaling pathway in
      Hassall's corpuscles of the human thymus.
AB  - In the present study, we investigated the immunohistochemical localization of
      mitogen-activated protein kinase (MAPK) signaling pathway in the human thymus.
      Three members of MAPK, the extracellular signal-regulated kinase (ERK), the c-Jun
      N-terminal kinase (JNK) and the p38 kinase, showed differential expression
      patterns in the thymus medulla. The phosphorylated form of ERK (p-ERK) was
      abundantly present in the outer layer of Hassall's corpuscles, and the
      phosphorylated form of p38 kinase (p-p38 kinase) was present in the entire
      Hassall's corpuscles. The phosphorylated form of JNK (p-JNK) was expressed in
      medullary thymocytes. We also examined localization of MAPK kinases (MAPKK or
      MEK) which specifically activate MAPK. MEK1, an activator of ERK, was found in
      the outer layer of Hassall's corpuscles where p-ERK was expressed. MEK3, an
      activator of p38 kinase, was also expressed in the outer layer. MEK4 and MEK7,
      which are activators of JNK, were present in the entire Hassall's corpuscles.
      Thus, differential expression of MAPK in the thymus supports the concept that the
      MAPK signaling pathway controls the specificity of functional thymic responses to
      extracellular stimuli. Furthermore, the abundant expression of various elements
      of the pathway in Hassall's corpuscles suggests that the pathway is involved in
      thymic medullary epithelial maturation.

PMID- 11252632
TI  - Histochemistry of lectin-binding sites in Halicryptus spinulosus (Priapulida).
AB  - Priapulida represent one of the phylogenetically oldest multicellular animal
      groups. In multicellular animals (Metazoa) cell-to-cell and cell-to-matrix
      interactions are often mediated by carbohydrate residues of glycoconjugates. To
      analyze the carbohydrate composition of a phylogenetically old species, lectin
      histochemistry was employed on 5 specimens of the priapulid Halicryptus
      spinulosus. Many lectins bound to the chitin-containing cuticle, including those
      specific for carbohydrates other than N-acetylglucosamine, the principle building
      block of chitin. The connective tissue of the animals contained both N
      acetylglucosamine and N-acetylgalactosamine. Mannose residues were widely
      distributed with the exception of the cuticle, but complex type carbohydrates
      were not present in the entire animal. Sialic acid residues were only detected in
      the cuticle and brush border of the intestinal epithelium, while fucose was
      limited to the cuticle. Thus, the lectin-binding pattern indicated that sugars
      typical for the linking region of both N- and O-glycoproteins in mammals are also
      present in H. spinulosus. Carbohydrate residues that are typical for the complex
      type of N-linked glycans in vertebrates are not present as are carbohydrate
      residues typical for the termination of O-linked carbohydrate chains. Hence, a
      truncated form of both N- and O-linked glycosylation is present in H. spinulosus
      indicating that more complex patterns of glycosylation developed later during
      evolution.

PMID- 11252633
TI  - Multiple forms of glycoproteins in the secretory product of the bovine
      subcommissural organ--an ancient glial structure.
AB  - The glial subcommissural organ (SCO) is a conserved structure of the vertebrate
      brain that secretes a glycoprotein-rich product into both the extracellular
      matrix and the cerebrospinal fluid of the third ventricle that forms Reissner's
      fibre (RF). In order to identify specific secretory proteins of the
      subcommissural organ, a panel of antigen- and epitope-specific monoclonal
      antibodies was raised against bovine RF to study the distribution of epitopes in
      Western blots of bovine RF. Six groups of epitopes that were specific for SCO
      secretion were distinguished on the basis of their phylogenetic conservation and
      their different grades of resistance against chemical denaturation. The
      monoclonal antibody aRFME 4 recognised a carbohydrate-containing epitope that was
      strongly conserved in vertebrates and unique for SCO secretion. All epitopes
      showed essentially the same distribution pattern over 15 bovine RF glycoprotein
      fractions of different molecular masses in immunoblots indicating that the
      different RF fractions are closely related. They may represent multiple forms of
      SCO spondin.

PMID- 11252634
TI  - Mechanisms to synchronize neuronal activity.
AB  - Temporal aspects of neuronal activity have received increasing attention in
      recent years. Oscillatory dynamics and the synchronization of neuronal activity
      are hypothesized to be of functional relevance to information processing in the
      brain. Here we review theoretical studies of single neurons at different levels
      of abstraction, with an emphasis on the implications for properties of networks
      composed of such units. We then discuss the influence of different types of
      couplings and choices of parameters to the existence of a stable state of
      synchronous or oscillatory activity. Finally we relate these theoretical studies
      to the available experimental data, and suggest future lines of research.

PMID- 11252635
TI  - Reliable short-term memory in the trion model: toward a cortical language and
      grammar.
AB  - It has previously been shown that Hebb learning in a single column in the trion
      model of cortical organization occurs by selection. Motivated by von Neumann's
      solution for obtaining reliability and by models of circulating cortical
      activity, we introduce Hebb intercolumnar couplings to achieve dramatic
      enhancements in reliability in the firing of connected columns. In order for
      these enhancements to occur, specific temporal phase differences must exist
      between the same inherent spatial-temporal memory patterns in connected columns.
      We then generalize the criteria of large enhancements in the global firing of the
      entire connected columnar network to investigate the case when different inherent
      memory patterns are in the columns. The spatial rotations as well as the temporal
      phases now are crucial. Only certain combinations of inherent memory patterns
      meet these criteria with the symmetry properties playing a major role. The
      columnar order of these memory patterns not in the same symmetry family can be
      extremely important. This yields the first higher-level architecture of a
      cortical language and grammar within the trion model. The implications of this
      result with regard to an innate human language and grammar are discussed.

PMID- 11252636
TI  - Statistical characteristics of climbing fiber spikes necessary for efficient
      cerebellar learning.
AB  - Mean firing rates (MFRs), with analogue values, have thus far been used as
      information carriers of neurons in most brain theories of learning. However, the
      neurons transmit the signal by spikes, which are discrete events. The climbing
      fibers (CFs), which are known to be essential for cerebellar motor learning, fire
      at the ultra-low firing rates (around 1 Hz), and it is not yet understood
      theoretically how high-frequency information can be conveyed and how learning of
      smooth and fast movements can be achieved. Here we address whether cerebellar
      learning can be achieved by CF spikes instead of conventional MFR in an eye
      movement task, such as the ocular following response (OFR), and an arm movement
      task. There are two major afferents into cerebellar Purkinje cells: parallel
      fiber (PF) and CF, and the synaptic weights between PFs and Purkinje cells have
      been shown to be modulated by the stimulation of both types of fiber. The
      modulation of the synaptic weights is regulated by the cerebellar synaptic
      plasticity. In this study we simulated cerebellar learning using CF signals as
      spikes instead of conventional MFR. To generate the spikes we used the following
      four spike generation models: (1) a Poisson model in which the spike interval
      probability follows a Poisson distribution, (2) a gamma model in which the spike
      interval probability follows the gamma distribution, (3) a max model in which a
      spike is generated when a synaptic input reaches maximum, and (4) a threshold
      model in which a spike is generated when the input crosses a certain small
      threshold. We found that, in an OFR task with a constant visual velocity,
      learning was successful with stochastic models, such as Poisson and gamma models,
      but not in the deterministic models, such as max and threshold models. In an OFR
      with a stepwise velocity change and an arm movement task, learning could be
      achieved only in the Poisson model. In addition, for efficient cerebellar
      learning, the distribution of CF spike-occurrence time after stimulus onset must
      capture at least the first, second and third moments of the temporal distribution
      of error signals.

PMID- 11252637
TI  - A muscle activation model of variable stimulation frequency response and
      stimulation history, based on positive feedback in calcium dynamics.
AB  - Muscle fiber response to a train of variable-frequency pulses includes the
      potentiation and catch-like effect. For better understanding of these phenomena,
      we built an activation model with emphasis on the calcium liberation from and re
      sequestration into the sarcoplasmic reticulum, including calcium-induced calcium
      release. The model had two stable equilibrium points in the calcium
      concentration. Changes from the low to the high equilibrium point could be
      produced by high-frequency trains of pulses and would account for the
      potentiation. The model also showed a catch-like effect, as a long-lasting
      increment of muscle force after the application of a single extra pulse. The
      increase in force appeared in resting muscle, disappeared when the muscle was
      potentiated, and reappeared briefly if the stimulation was continued for long
      periods.

PMID- 11252638
TI  - Principles underlying mammalian neocortical scaling.
AB  - The neocortex undergoes a complex transformation from mouse to whale. Whereas
      synapse density remains the same, neuron density decreases as a function of gray
      matter volume to the power of around -1/3, total convoluted surface area
      increases as a function of gray matter volume to the power of around 8/9, and
      white matter volume disproportionately increases as a function of gray matter
      volume to the power of around 4/3. These phylogenetic scaling relationships
      (including others such as neuron number, neocortex thickness, soma radius, and
      number of cortical areas) are clues to understanding the principles driving
      neocortex organization, but there is currently no theory that can explain why
      these neocortical quantities scale as they do. Here I present a two-part model
      that explains these neocortical allometric scaling laws. The first part of the
      model is a special case of the physico-mathematical model recently put forward to
      explain the quarter power scaling laws in biology. It states that the neocortex
      is a space-filling neural network through which materials are efficiently
      transported, and that synapse sizes do not vary as a function of gray matter
      volume. The second part of the model states that the neocortex is economically
      organized into functionally specialized areas whose extent of area
      interconnectedness does not vary as a function of gray matter volume. The model
      predicts, among other things, that the number of areas and the soma radius
      increase as a function of gray matter volume to the power of 1/3 and 1/9,
      respectively, and empirical support is demonstrated for each. Also, the scaling
      relationships imply that, although the percentage of the total number of neurons
      to which a neuron connects falls as a function of gray matter volume with
      exponent -1/3, the network diameter of the neocortex is invariant at around two.
      Finally, I discuss how a similar approach may have promise in explaining the
      scaling relationships for the brain and other organs as a function of body mass.

PMID- 11252639
TI  - Analysis of kinematically redundant reaching movements using the equilibrium
      point hypothesis.
AB  - Six subjects performed a planar reaching arm movement to a target while
      unpredictable perturbations were applied to the endpoint; the perturbations
      consisted of pulling springs having different stiffness. Two conditions were
      applied; in the first, subjects had to reach for the target despite the
      perturbation, in the second condition, the subjects were asked to not correct the
      motion as a perturbation was applied. We analyzed the kinematics profiles of the
      three arm segments and, by means of inverse dynamics, calculated the joint
      torques. The framework of the equilibrium-point (EP) hypothesis, the lambda
      model, allowed the reconstruction of the control variables, the "equilibrium
      trajectories", in the "do not correct" condition for the wrist and the elbow
      joints as well as for the end point final position, while for the other
      condition, the reconstruction was less reliable. The findings support and extend
      to a multiple-joint planar movement, the paradigm of the EP hypothesis along with
      the "do not correct" instruction.

PMID- 11252640
TI  - Frequency sensitivity in Hodgkin-Huxley systems.
AB  - The frequency sensitivity of weak periodic signal detection has been studied via
      numerical simulations for both a single neuron and a neuronal network. The
      dependence of the critical amplitude of the signal upon its frequency and a
      resonance between the intrinsic oscillations of a neuron and the signal could
      account for the frequency sensitivity. In the presence of both a subthreshold
      periodic signal and noise, the signal-to-noise ratio (SNR) of the output of
      either a single neuron or a neuronal network present the typical characteristics
      of stochastic resonance. In particular, there exists a frequency-sensitive range
      of 30-100 Hz, and for signals with frequencies within this range the SNRs have
      large values. This implies that the system under consideration (a single neuron
      or a neuronal network) is more sensitive to the detection of periodic signals,
      and the frequency sensitivity may be of a functional significance to signal
      processing.

PMID- 11252641
TI  - Perspectives for clinical research on bipolar disorders in the new millennium.

PMID- 11252642
TI  - Emerging trends in the treatment of rapid cycling bipolar disorder: a selected
      review.
AB  - Recent evidence suggests that lithium therapy (even as supplemented by
      antidepressants and neuroleptics) is inadequate for the majority of patients with
      bipolar illness, and particularly those with rapid cycling. Valproate and
      carbamazepine have emerged as adjuncts and alternatives, but they, too, often
      require additional approaches with lithium, thyroid hormones, and other putative
      mood stabilizers, including nimodipine (and related dihydropyridine calcium
      channel blockers), lamotrigine, gabapentin, topiramate, and the atypical
      neuroleptics. Evaluating how these agents and the unimodal antidepressants are
      optimally applied and sequenced in the treatment of bipolar illness with its
      multiple subtypes, patterns and comorbidities will require much future
      investigation and the development of new methodological clinical trial
      approaches.

PMID- 11252643
TI  - A theoretical reappraisal of mixed states: dysphoria as a third dimension.
AB  - Mixed states are heterogeneous clinical entities difficult to define precisely.
      The stringent actual DSM IV criteria are unsatisfactory for current clinical use.
      Many frequently encountered mixed patients benefit without an accurate diagnosis
      from biological therapeutic interventions such as the introduction of mood
      stabilizers. We propose a brief review of the definition and characteristics of
      mixed states and propose a new approach to the typology of mixed states. Based on
      recent literature data, we add to the depressive and manic syndrome the concept
      of dysphoria as a third dimension. Integrating this three dimensional approach
      with recent factor analysis, we describe in addition to the DSM IV mixed state
      (type I) two new subtypes of mixed states (type IIM and IID). This new typology
      can give the clinician a more accurate understanding of the complex and
      polymorphous reality of mixed states and help him make more specific therapeutic
      interventions. These subtypes of mixed states will need validation through
      prospective clinical studies. Biological differences, differential outcome over
      time, and differential response to treatment will be important validation
      criteria.

PMID- 11252644
TI  - Depression, mania, and feeling bad: the role of dysphoria in mixed states.

PMID- 11252645
TI  - No evidence of association from transmission disequilibrium analysis of the hKCa3
      gene in bipolar disorder.
AB  - OBJECTIVE: A recent case control study has suggested that modest enlargements of
      a highly polymorphic CAG repeat in exon 1 of the gene encoding potassium channel
      hKCa3 may be associated with bipolar disorder (BPD). We have examined this
      hypothesis by genotyping this locus in a family-based association study. METHOD:
      One hundred and twenty-eight parent offspring trios of British Caucasian origin
      were examined where the proband was diagnosed with the American Psychiatric
      Association's Diagnostic and Statistical Manual (DSM)-IV BPD I (n = 123) or II (n
      = 5). An improved assay was used, with redesigned polymerase chain reaction (PCR)
      primers, permitting quicker and higher resolution genotyping. The resultant
      genotypes were analysed using the extended transmission/ disequilibrium test
      (ETDT). RESULTS: The experimental data did not provide evidence for the
      preferential transmission of large alleles to bipolar cases (chi2 = 11.12, df =
      10, p = 0.349). CONCLUSIONS: Our data provide no support for the hypothesis that
      variation at the hKCa3 gene contributes to susceptibility to BPD.

PMID- 11252646
TI  - Response to placebo among bipolar I disorder patients experiencing their first
      manic episode.
AB  - BACKGROUND: The first episode of an illness may respond differently to any
      treatment compared to multiple episodes of the same illness. This study details
      the treatment response of six first-episode manic patients who participated in a
      previously reported study of 139 subjects comparing olanzapine to placebo in
      bipolar I mania (Tohen M, Sanger TM, McElroy SL, Tollefson GD, Chengappa KNR,
      Daniel DG. Olanzapine versus placebo in the treatment of acute mania. Am J
      Psychiatry 1999; 156: 702-709). METHODS: Six first-episode subjects participated
      in a 3-week double-blind, random assignment, parallel group, placebo-controlled
      study of olanzapine for bipolar mania. The Young Mania Rating Scale (Y-MRS),
      Clinical Global Impression, and Hamilton Depression ratings were administered
      weekly. Lorazepam as rescue medication was permitted for the first 10 days.
      RESULTS: Five subjects were randomized to placebo and one to olanzapine. Two
      subjects (40%) with psychotic mania (who also had their first-illness episode)
      were assigned to placebo and responded with greater than 50% reduction in the Y
      MRS score and also remitted in 3 weeks. Another placebo-assigned subject had a
      46% reduction in the Y-MRS scores, and two placebo-assigned subjects worsened.
      The olanzapine-assigned subject had a 44% reduction in the Y-MRS score. In
      contrast, 34 of 69 (48.6%) multiple-episode olanzapine subjects responded and 14
      of 61 (23.0%) of placebo-treated subjects did. CONCLUSIONS: This preliminary data
      set suggest there may be differences in treatment response between first-illness
      episode versus multi-episode bipolar manic subjects. Larger numbers of subjects
      with these illness characteristics are needed to either confirm or refute this
      suggestion.

PMID- 11252647
TI  - An open longitudinal study of patients with bipolar rapid cycling treated with
      lithium or lamotrigine for mood stabilization.
AB  - OBJECTIVES: Patients with rapid cycling bipolar disorder are frequently observed
      to fail conventional treatment. We conducted a preliminary study to explore the
      potential efficacy of lamotrigine in the treatment of this refractory patient
      population. METHODS: In an open longitudinal investigation, 14 patients with
      rapid cycling bipolar disorder were treated for 1 year with either lithium or
      lamotrigine as mood stabilizer. RESULTS: Out of the seven patients with lithium,
      three out of seven (43%) had less than four and four out of seven (57%) had four
      or more episodes. In the lamotrigine group, six out of seven (86%) had less than
      four and one out of seven (14%) had more than four affective episodes
      (depressive, manic, hypomanic or mixed). In fact, three out of seven (43%) of the
      patients who were on lamotrigine therapy were without any further affective
      episodes. There was no evidence of a preferential antidepressant versus antimanic
      efficacy. CONCLUSIONS: Although the study is limited by the small number of
      patients, the results are in line with other investigations, suggesting efficacy
      for lamotrigine and a suboptimal response for lithium in rapid cycling bipolar
      disorder. These preliminary data need to be confirmed with controlled double
      blind studies.

PMID- 11252648
TI  - The Internal State Scale: replication of its discriminating abilities in a
      multisite, public sector sample.
AB  - OBJECTIVE: The Internal State Scale (ISS) is a self-report instrument that has
      been validated for discriminating mood states in patients with bipolar disorder.
      This study a) extends investigation to a multisite public sector sample and b)
      tests a revised scoring algorithm that formally identifies patients in mixed
      states. METHODS: Eighty-six patients with bipolar disorder from four Veterans
      Affairs medical centers were assessed in a cross-sectional design. Physician
      conducted semi-structured interviews used DSM-IV criteria to identify subjects as
      meeting criteria for euthymia, mania or hypomania, depression, or mixed state
      (mania or hypomania plus depression). A revised ISS scoring algorithm
      independently assigned mood state. Mean subscale scores were analyzed across
      groups. Receiver-operating characteristic (ROC) curve analysis was conducted to
      determine optimal algorithm structure. RESULTS: Analysis of mean scores for the
      ISS subscales replicated original results for Activation, Well-Being, and
      Perceived Conflict, but indicated differences from the original results for the
      Depression Index. The ROC curve analysis identified optimal cut-off scores for
      the revised algorithm. The overall kappa score indicated moderate agreement
      between ISS and physician ratings of mood state, including mixed states.
      LIMITATIONS: The study used a sample consisting primarily of male veterans. Mood
      state was assigned by experts using expert clinician diagnosis, not structured
      interviews. CONCLUSION: The performance of the ISS in this multisite, public
      sector sample was similar to the performance in the initial research clinic
      sample. This finding confirms the validity of the ISS as a discriminator of mood
      states in bipolar disorder. The development of a revised scoring algorithm makes
      feasible formal identification of mixed episodes with the ISS.

PMID- 11252649
TI  - The high affinity inositol transport system--implications for the pathophysiology
      and treatment of bipolar disorder.
AB  - The 'inositol-depletion hypothesis' postulates that the therapeutic effects of
      lithium are due to inhibition of inositol monophosphatase, which leads to
      depletion of brain cells of myo-inositol and consequently to dampening of
      phosphoinositide (PI) signaling. This article examines the potential relevance of
      an alternative mechanism for inositol depletion: inhibition of myo-inositol
      uptake that proceeds via the sodium/myo-inositol cotransport (SMIT). We discuss
      recent in vitro experiments that show a pronounced downregulation of SMIT after
      chronic treatment with lithium, carbamazepine, and valproate at therapeutically
      relevant concentrations. It is concluded that downregulation of SMIT could
      represent a common mechanism of action of mood stabilizers.

PMID- 11252650
TI  - Calcium channel antagonists for the treatment of bipolar disorder.
AB  - Calcium channel antagonists (CCAs) have many clinical applications, including
      their possible use in the treatment of bipolar disorder. Two justifications for
      this last application are some overlap in physiological activities of CCAs with
      those of lithium, and a possible association between bipolar disorder and calcium
      dysregulation. While the data from earlier studies support the use of verapamil
      in treating bipolar mania. more recent better-controlled trials have not. This
      paper reviews the available body of data regarding CCAs in the treatment of
      bipolar disorder, concluding there is presently limited support for their
      efficacy.

PMID- 11252651
TI  - Psychotropic drug prescription patterns among patients with bipolar I disorder.
AB  - INTRODUCTION: Combination treatment, rather than monotherapy, is prevalent in the
      treatment of subjects with bipolar disorder, probably due to the complex and
      phasic nature of the illness. In general, prescription patterns may be influenced
      by the demographic characteristics of patients as well. We evaluated prescription
      patterns and the influence of demographic variables on these patterns in a
      voluntary registry of subjects with bipolar disorder. METHODS: A subset of data
      from a larger voluntary registry was extracted for demographic variables and
      psychotropic medication use that had been reported in the month prior to
      registration by ambulatory, non-hospitalized subjects with bipolar I disorder in
      1995/96 (n = 457). RESULTS: Among the thymoleptic agents, lithium was prescribed
      in over 50% of subjects, valproate in approximately 40%, and carbamazepine in 11%
      of subjects. Eighteen percent of subjects had no prescription for thymoleptic
      agents. Nearly one-third of all subjects were receiving antipsychotic agents, of
      whom two-thirds were receiving the traditional neuroleptic agents. More than half
      of all subjects were receiving concomitant antidepressants, of whom nearly 50%
      received the SSRI antidepressants and nearly 25% received buproprion.
      Approximately 40% of subjects received benzodiazepines. Only 18% of subjects
      received monotherapy, and nearly 50% received three or more psychotropic agents.
      In general, no associations were noted between demographic parameters including
      age, gender, marital or educational status, and psychotropic prescriptions.
      CONCLUSION: Consistent with the anecdotal reports, these data confirm that
      combination treatment is far more common than monotherapy. Demography appears to
      have a minimal impact on cross-sectional prescription patterns in subjects with
      bipolar disorder. Given that combination treatments are the rule rather than the
      exception, we should strive to achieve rational, yet pragmatic, treatment
      guidelines and algorithms to minimize the risks while maximizing the benefits of
      these combination treatments for patients with bipolar disorder.

PMID- 11252652
TI  - Relationship of childhood physical and sexual abuse to adult bipolar disorder.
AB  - OBJECTIVES: To characterize whether adult depressives with either bipolar or
      unipolar disorder differ in the prevalence of childhood sexual or physical abuse.
      METHOD: The investigators reviewed data from patients who were evaluated over a 2
      year period by a semi-structured clinical interview. In total, 333 cases with a
      bipolar or unipolar diagnosis were included in the present study. RESULTS: A
      childhood history of abuse, in particular sexual abuse, was significantly more
      frequent in bipolar subjects compared with unipolar subjects. Consistent with
      previous studies, women reported higher rates of sexual abuse than men, although
      no interaction by diagnosis was shown. Sexual abuse incidence in male samples was
      markedly dissimilar, with male bipolar subjects demonstrating a significantly
      increased rate of sexual abuse and combined sexual and physical abuse compared
      with unipolar male subjects. CONCLUSION: The increased incidence of sexual abuse
      in women supports growing evidence of gender differences in sexual abuse among
      adult depressives. In contrast to literature reports, the finding that male
      bipolar patients have significantly increased rates of sexual abuse histories
      suggests differences in psychiatric depressive subgroups. This result may reflect
      the particular characteristics of our cohort (treatment resistant, privately
      insured, and educated). Further work will aid in characterizing sexual abuse
      prevalence in other male bipolar samples.

PMID- 11252653
TI  - Clinical characteristics of familial and non-familial bipolar disorder.
AB  - OBJECTIVE: To explore the clinical characteristics of familial and non-familial
      bipolar disorder. METHOD: Twenty subjects with bipolar disorder, who also had a
      family history of bipolar disorder in a first degree relative, were matched for
      current age, age of first onset of bipolar disorder and gender with 20 subjects
      with bipolar disorder who had no family history of any psychiatric disorders in
      first or second degree relatives. RESULTS: Fourteen subjects in each group were
      female. The mean age at interview was 45.2 years and the mean age at first
      admission was 26 years. Although familial and non-familial probands had an
      equivalent number of illness episodes, familial probands were significantly more
      likely to experience mixed states as compared to non-familial probands. The
      latter experienced significantly more depressive episodes and had significantly
      higher neuroticism (N) scores on the Eysenck Personality Inventory (EPI; Eysenck
      H, Eysenck S. Manual of the Eysenck Personality Inventory. London: University of
      London Press, 1964.). CONCLUSIONS: If the results are replicated, they have
      important implications. For example, such data may aid decisions about the
      targeting of additional psychosocial interventions in high N score cases.
      Researchers will wish to investigate whether mixed states show a stronger
      association with early age of onset or family history of BD.

PMID- 11252654
TI  - Can the expression of histocompatibility antigen be changed by lithium?
AB  - OBJECTIVES: This study attempted to determine whether human leukocyte antigen
      (HLA) type changes would be caused by lithium. METHODS: A total of 15 patients
      were chosen as subjects (4 males, 11 females) and completed tests in class I.
      Eight of the 15 patients completed tests in class II. Their mean age was 27 +/- 7
      years. For an average of 51 +/- 17 days, lithium, 600-1,200 mg/day (mean daily
      dose: 920 +/- 211 mg) was administered for the HLA testing and then compared with
      the HLA type prior to the time the drug was administered. Class I type test was
      performed according to the Terasaki microcytotoxicity method and class II type by
      the Erlich polymerase chain reaction method. RESULTS: Of the 15 subjects, 11 had
      changes in HLA-A, B, C types and two of the eight subjects had changes in HLA DR
      type. CONCLUSION: Lithium, in the therapeutic dose, is considered to bring about
      changes in HLA expressions in as short a time period as 2 months.

PMID- 11252655
TI  - Serotonin in mania and in the mechanism of action of mood stabilizers: a review
      of clinical studies.
AB  - OBJECTIVES: Serotonin (5-hydroxytryptamine, 5-HT) was implicated in the
      pathophysiology of manic-depressive illness as early as 1958. Although extensive
      evidence has accumulated since then to support 5-HT's role in depression,
      relatively fewer studies examined its role in mania. The purpose of this paper
      was to review and summarize the current state of knowledge on the role of 5-HT in
      mania and its treatment. METHODS: We systemically reviewed clinical studies of 1)
      5-HT function in mania and 2) 5-HT in the mechanism of action of mood
      stabilizers, including lithium and anticonvulsants. RESULTS: Review showed that
      cerebrospinal fluid, postmortem, platelet, neuroendocrine challenge, and
      tryptophan depletion studies provided some evidence to support the hypothesis
      that a 5-HT deficit is involved in mania and that enhancement of 5-HT
      neurotransmission exerts a mood-stabilizing effect. CONCLUSIONS: There is some
      evidence from clinical studies for the contribution of 5-HT in mania and in the
      mechanism of action of mood stabilizers. However, it is very likely that other
      neurotransmitters also play important roles. Future directions for research
      include 1) in vivo study of 5-HT receptor subtypes using positron emission
      tomography, 2) investigation of the interaction between 5-HT and other
      neurotransmitter systems, and 3) determination of the relationships between
      diagnostic subtypes of mania and 5-HT function and other neurotransmitter
      systems.

PMID- 11252656
TI  - The impact of lithium prophylaxis on the course of bipolar disorder: a review of
      the research evidence.
AB  - A critical review is provided of the available research evidence concerning the
      efficacy and effectiveness of lithium prophylaxis in bipolar disorder. It is
      emphasized that, in spite of the limitations of available placebo-controlled
      trials and naturalistic studies, lithium is the only drug whose prophylactic
      activity in bipolar disorder is convincingly proved, and remains the first-choice
      medication in the long-term treatment of bipolar patients. The impact of lithium
      prophylaxis is likely to be less significant on atypical and comorbid cases of
      bipolar disorder than in typical manic depressive illness, but the superiority of
      other medications over lithium in the long-term treatment of those cases is at
      present not convincingly proved by research. Currently available research
      evidence does not seem to support the idea that lithium exerts its prophylactic
      effect on relapses but not on recurrences of bipolar disorder. Clinicians should
      be aware of the fact that the drop-out rate in bipolar patients receiving long
      term lithium prophylaxis is high even if treatment surveillance is accurate, and
      that complete suppression of recurrences is a relatively rare outcome of
      prophylaxis.

PMID- 11252657
TI  - Prophylactic efficacy of lithium administered every second day: a WHO multicentre
      study.
AB  - OBJECTIVES: To study the prophylactic efficacy of lithium administered every
      second day to patients with bipolar disorder or recurrent unipolar depressive
      disorder. METHODS: The study was carried out as a WHO multicentre study in five
      different psychiatric clinics: Russia (Moscow), Canada (Montreal), India
      (Lucknow), Germany (Munich) and South Korea (Pusan), with the lithium tablets
      being supplied from Denmark (Copenhagen). Participation in the study was
      conditional on the patient having been in prophylactic lithium treatment for the
      preceding 2-year period and having been free of depressive or manic phases during
      the preceding 6 months. After a 2-month baseline period during which lithium was
      administered every day, the treatment was changed to lithium intake every second
      day, this regimen in most cases being continued for 22 months. RESULTS: Forty
      seven patients, 42 with a diagnosis of bipolar disorder and five with a diagnosis
      of recurrent unipolar depressive disorder, participated in the study. The number
      of patients from each centre ranged from six to 11. The mean lithium dose every
      second day was 36 mmol lithium, leading to a mean 12-h standard serum lithium
      concentration during the last month of treatment at 0.78+/-0.16 mmol/L. Lithium
      intake every second day was effective in 38 out of 47 patients. The remaining
      nine patients had recurrences, a number not differing from the 16 patients in the
      same group of 47 patients who, during the 2-year period preceding the study, had
      recurrences. The mean 12-h standard serum lithium concentration was lower in the
      patients who had recurrences than in those who stayed euthymic. The results
      suggest that to be effective when administered every second day, lithium must be
      given in a dose leading to a 12-h standard serum lithium concentration at 0.8
      mmol/L or above. CONCLUSIONS: In the dose administered, lithium intake every
      second day was as effective as lithium intake every day. The amount and severity
      of lithium-related side effects were apparently not influenced by the change to
      lithium intake every second day.

PMID- 11252659
TI  - Clozapine associated with decreased suicidality in bipolar disorder: a case
      report.

PMID- 11252660
TI  - Lithium therapy at the millennium: a revolutionary drug used for 50 years faces
      competing options and possible demise.

PMID- 11252658
TI  - "A two-illness model of bipolar disorder"--by RT Joffe, LT Young, and GM
      MacQueen: a commentary.

PMID- 11252661
TI  - Antibipolar potential for transcranial magnetic stimulation.

PMID- 11252662
TI  - Repetitive transcranial magnetic stimulation: perspectives for application in the
      treatment of bipolar and unipolar disorders.
AB  - OBJECTIVES: Transcranial magnetic stimulation (TMS) affects the brain by non
      invasively stimulating the cerebral cortex and inducing electrical currents in
      neurons. The powerful magnetic field acts as a vector that passes across the
      scalp and the skull, and then converts into an electrical energy within the
      brain. Originally used in neurophysiology, TMS has since been applied in a
      variety of neuropsychiatric conditions, including mood disorders. Imaging studies
      in mood-disordered patients have pointed to dysfunctional limbic and prefrontal
      cortex activity. TMS researchers have thus postulated that dorsolateral
      prefrontal cortex (DLPFC) stimulation might change brain activity both locally
      and in paralimbic areas through transynaptic connections, and alter mood.
      METHODS: We will describe the technology of TMS, its applications to date, and
      explore its mechanisms of action. RESULTS: Several clinical trials have
      demonstrated TMS effects on mood in health and disease. There is a growing
      consensus that TMS has antidepressant effects, although little is known about the
      role played by a variety of stimulation parameters such as the intensity or
      frequency of stimulation. One study has found an antimanic effect of right
      prefrontal TMS. CONCLUSION: TMS is relatively safe; however, much more research
      is needed before TMS can be integrated into routine clinical practice.

PMID- 11252663
TI  - Abnormalities in protein kinase C signaling and the pathophysiology of bipolar
      disorder.
AB  - Protein kinase C (PKC) is a group of calcium and phospholipid-dependent enzymes,
      which plays a pivotal role in cell signaling systems. Recently accumulated
      evidence indicates that alterations in PKC activity play a significant role in
      the pathophysiology of bipolar disorder. A number of laboratories investigated
      the effect of mood stabilizers on the regulation of PKC activity in bipolar
      patients, in animals, and in cultured cells. Following chronic lithium treatment,
      PKC activation was significantly reduced in rat brains, as measured by the
      translocation of cytoplasmic PKC to the membrane compartment, or by quantitative
      binding of the PKC ligand, PDBu. The effect of the therapeutic concentration of
      lithium in attenuating PKC-dependent intracellular parameters was also
      demonstrated in cultured cells. More importantly, alterations in platelet PKC was
      shown in bipolar patients during the manic state of the illness. In comparison to
      patients with major depressive disorder, schizophrenia, or healthy controls, PKC
      activity was significantly increased in manic patients, suggesting that changes
      in PKC may be an illness-specific marker. Interestingly, enhanced PKC activity
      during mania was suppressed following mood-stabilizer treatment as manic symptoms
      improved. In parallel to the findings in platelets, postmortem studies
      demonstrate that membrane-associated PKC and stimulation-induced translocation of
      cytosolic enzyme to the membrane were also increased in frontal cortex of bipolar
      patients. Other studies suggest alterations in other signal transduction
      mechanisms in bipolar disorder. These include alterations in G protein
      activation, phosphatidylinositol (PI) signaling, cyclic AMP formation, and
      intracellular calcium homeostasis. The alterations of PKC activity in bipolar
      disorder may be related to changes in these other intracellular signaling
      mechanisms. Alternatively, the changes of PKC activity may be the core pathology
      of the illness. More studies are required to further characterize the association
      of PKC changes with bipolar disorder, using a proper neuronal model.

PMID- 11252664
TI  - Lithium and synaptic plasticity.
AB  - Lithium, a small cation, has been used in the treatment of bipolar disorders
      since its introduction in the 1950s by John Cade. Extensive research on the
      mechanism of action of lithium has revealed several possible targets. For some
      time, the most widely accepted action of lithium was its inhibitory effect on the
      synthesis of inositol, resulting in depletion of inositol with profound effects
      on neuronal signal transduction pathways. However, several studies show that some
      effects of lithium are not mediated through inositol depletion. Recent findings
      demonstrate that lithium directly inhibits, in a non-competitive fashion, the
      activity of glycogen synthase kinase (GSK)-3beta, a serine/threonine kinase
      highly expressed in the central nervous system. Interestingly, inhibition of GSK
      3beta has been shown to regulate neuronal plasticity by inducing axonal
      remodelling and increasing the levels of synaptic proteins. These findings raise
      the possibility for developing new therapeutic approaches for the treatment of
      bipolar disorders.

PMID- 11252665
TI  - Latency and episodes before treatment: response to lithium maintenance in bipolar
      I and II disorders.
AB  - OBJECTIVES: To test whether longer treatment-delays or more pretreatment illness
      episodes are followed by diminished response to lithium maintenance. METHODS: In
      360 DSM-IV bipolar I (n = 220) or II (n = 140) patients, effects of latency from
      illness onset to starting lithium and number of pretreatment episodes were
      evaluated by survival analysis based on the number of months stable before a
      first recurrence on lithium. Factors associated with treatment latency were
      identified by regression modeling. Relationships of time, episode number, and
      morbidity before treatment to the overall proportion of time ill on lithium were
      also tested by nonparametric correlation. RESULTS: Latency to first lifetime
      lithium maintenance averaged 8.3 years, with 9.3 episodes/subject. Time stable
      before a first recurrence on lithium averaged 29.6 months and was unrelated to
      treatment latency (in terciles) or to a high (> or = ten), intermediate (four
      nine), or low (< four) number of prior episodes. Overall morbidity during 4.6
      years of lithium maintenance was also unrelated to these pretreatment factors.
      More episodes/year and percentage of time ill before treatment anticipated
      shorter treatment latency, with greater relative improvement, but were unrelated
      to morbidity during treatment. CONCLUSIONS: Treatment latency and prelithium
      episode number were unrelated to morbidity during treatment. Although multiple
      untreated episodes can lead to severe disability, lithium evidently can greatly
      limit morbidity, even after years of delay and multiple episodes of bipolar
      illness.

PMID- 11252666
TI  - Myers Briggs Type Indicator and Tridimensional Personality Questionnaire
      differences between bipolar patients and unipolar depressed patients.
AB  - OBJECTIVES: The current study was designed to compare personality differences
      between bipolar patients and unipolar depressed patients, as evaluated on the
      Myers Briggs Type Indicator (MBTI) and the Tridimensional Personality
      Questionnaire (TPQ). METHODS: A group of bipolar and a group of unipolar
      depressed patients filled out the MBTI, the TPQ, the Beck Depression Inventory,
      and the CAGE questionnaire. The two groups were compared with each other as to
      responses on the above surveys, and subgroups of bipolar depressed and bipolar
      patients with manic symptoms were also compared. RESULTS: Bipolar patients were
      found to be significantly more extroverted (p = 0.004) and less judging (p =
      0.007) on the MBTI. They were significantly more novelty seeking (p = 0.004) and
      less harm avoidant (p = 0.002) on the TPQ. Of the above differences, only the TPQ
      harm avoidance scale appeared strongly linked to the patients' level of
      depression. CONCLUSION: Significant differences in personality exist between
      bipolar disorder and unipolar depressed patients.

PMID- 11252667
TI  - Vaccinia virus recombinants encoding the truncated structural gene region of
      Venezuelan equine encephalitis virus (VEEV) give solid protection against
      peripheral challenge but only partial protection against airborne challenge with
      virulent VEEV.
AB  - Vaccinia virus (VV) recombinants that contain the genes encoding the Venezuelan
      equine encephalitis virus (VEEV) structural gene region (C-E3-E2-6 K-E1) solidly
      protect mice against peripheral challenge with virulent VEEV, but provide only
      partial protection against airborne challenge. To improve upon these results we
      focussed on the principal antigens involved in protection. VV recombinants
      encoding the structural genes E3-E2-6 K-E1, E3-E2-6 K or 6 K-E1 were prepared and
      evaluated for their ability to protect Balb/c mice after a single dorsal
      scarification with 10(8) PFU against peripheral or airborne challenge with
      virulent VEEV. The antibody response was also examined. Our experiments provide
      new evidence that truncates of the VEEV structural region (E3-E2-6 K-E1, E3-E2-6
      K), cloned and expressed in VV, protect against challenge with virulent virus.
      They also confirm the important role of E2 in protection. However, we were unable
      to improve upon previously reported levels of protection against airborne
      challenge. A substantial level of circulating antibodies and the presence of
      local IgA (not always induced by mucosal immunization) (Greenway et al., 1992)
      appear essential for protection against the airborne virus. Current VV-VEEV
      recombinants seem unable to elicit this level of immune response and further
      improvements are therefore required to increase the immunogenicity of VV-VEEV
      vaccines.

PMID- 11252668
TI  - Amino acid changes in the hemagglutinin and matrix proteins of influenza a (H2)
      viruses adapted to mice.
AB  - Mouse-adapted (MA) variants of human and avian influenza A (H2) viruses were
      generated and characterized with respect to acquisition of virulence in mice.
      From the nucleotide sequence the amino acid sequence was deduced. The HA1 subunit
      of the hemagglutinin (HA) contained three amino acid substitutions in the A/black
      duck/New Jersey/1580/78-MA variant (Glu216-->Asp, Lys307-->Arg, and Thr318-->Ile)
      and two substitutions in the A/JapanxBellamy/57-MA variant (Lys25-->Thr and
      Ser203-->Phe). In the M1 protein, there were two substitutions in the A/black
      duck/New Jersey/1580/78-MA variant (Asn30-->Asp and Gln214-->His) and a single
      substitution in the A/JapanxBellamy/57-MA variant (Met179-->Lys). The M2 protein
      amino acid sequences of the parental virus and the MA variants differed by a
      single identical mutation (Asn93-->Ser). The localization and atomic distances of
      the observed mutations on the three-dimensional (3D) structure of the HA protein
      were analyzed for influenza H2 viruses. The obtained results were similar to
      those published earlier on H1, H3 and H5 subtypes. The amino acid changes in the
      HA protein could be divided into two groups. In one group the substitutions were
      situated at the top of the molecule, while in the other group they were clustered
      in the stem area at the interface region between three HA monomers. The analysis
      revealed that the substitutions observed in the MA variants probably increase the
      flexibility of the HA molecule and/or weaken the interactions between monomers or
      subunits in the HA trimer. The relationships of the observed amino acid changes
      in the HA and M proteins to the biological properties of the respective viruses
      and possible mechanisms involved in the acquisition of viral virulence are
      discussed.

PMID- 11252669
TI  - The glycosylation status and the role of carbohydrate moieties in the
      heterogeneity of cucumber anionic virus-inducible peroxidase.
AB  - Three forms of anionic peroxidase (PRX) from hypersensitively reacting cucumber
      cotyledons were purified to homogeneity and different methods were used to
      analyze the nature of their carbohydrate chains. Immunoblot analysis with betaF1
      antiserum showed that all three forms are highly glycosylated and contain
      asparagine N-linked glycans commonly found in other plant glycoproteins. Mobility
      shift analysis showed that chemical deglycosylation converted PRXs 1, 2 and 3 to
      the same-sized (35 K) products. Enzymatic deglycosylation with alpha-mannosidase
      converted PRX1 and PRX2 to immunoreactive products migrating in mobility shift
      polyacrylamide gels at the positions of PRX2 and PRX3, respectively. PRX3 treated
      with alpha-mannosidase yielded a product with Mr similar to that obtained with
      the chemical deglycosylation. Cleavage of the PRXs 1, 2 and 3 by formic acid at
      the Asp-Pro site resulted in peptide maps and the putative glycopeptide(s) were
      recognized using betaF1 antiserum. Only one glycopeptide was observed for each of
      the forms. Lectin-affinity blot analysis using biotin-conjugated lectins
      suggested that virus-inducible PRX contains complex-type N-glycosyl carbohydrate
      chain(s). These results indicate that heterogeneity of cucumber virus-inducible
      PRX is not caused mainly by differences in the terminal alpha-linked mannose
      residues.

PMID- 11252670
TI  - Development of probes for differentiation of infectious bursal disease virus
      strains of various virulence by dot-blot hybridization.
AB  - Two different radio-labeled nucleic acid probes, prepared from reverse
      transcription-polymerase chain reaction (RT-PCR) amplified variable region of VP2
      and VP1 gene sequences of a highly virulent infectious bursal disease virus
      (IBDV), were tested for their ability to detect field isolates of IBDV directly
      in clinical bursal tissue specimens and vaccine strains of IBDV in tissue
      cultures. The VP2 gene probe was able to detect both field isolates and vaccine
      strains of IBDV under high as well as low stringency while the VP1 gene probe
      could differentiate under high stringency field isolates from vaccine strains,
      hybridizing only with RNA of field isolates. The sensitivity of both the probes
      was found to be 4 ng of purified viral RNA.

PMID- 11252672
TI  - Transcription and replication of the influenza a virus genome.
AB  - The genome of influenza A virus consists of eight segments of negative-strand
      viral RNA (vRNA). During the replication cycle of the virus, the genomic vRNA is
      transcribed into positive-strand mRNA and complementary RNA (cRNA) in the cell
      nucleus. The promoter for the synthesis of mRNA molecules is located in a
      partially double-stranded RNA structure formed by the 5'- and 3'-terminal
      sequences of genomic vRNA segments. The virus encoded RNA-dependent RNA
      polymerase complex has to interact with both ends of the vRNA in order to
      generate capped RNA primers by endonucleolytic cleavage of cellular pre-mRNAs for
      the initiation of viral mRNA synthesis. Conserved sequence elements in the 5'
      end, e.g. a polymerase binding site and a U(5-7) sequence are required for
      polyadenylation of virus-specific mRNAs. Polyadenylation occurs by reiterative
      copying of the U(5-7) sequence by the viral RNA polymerase, which is bound to the
      5'end of the vRNA template. The U(5-7) sequence acts directly as a template for
      the poly(A)-tail. During the replication cycle of the virus, a "switch" from mRNA
      to cRNA synthesis occurs, but the mechanism by which this switch occurs remains
      unclear. The viral nucleoprotein and its interaction with the polymerase proteins
      and vRNA might play a role in this process. In contrast to transcription, the
      process of replication--the synthesis of cRNA and vRNA, which are known to occur
      in the absence of primers--is poorly understood.

PMID- 11252671
TI  - Prevalence and genomic variation of Norwalk-like viruses in central Australia in
      1995-1997.
AB  - Norwalk-like viruses (NLVs) have now been found to be important causes of
      gastroenteritis amongst infants and young children as well as older children and
      adults. Although detected, such viruses appeared not to be a major cause amongst
      infants and young children hospitalized with gastroenteritis in Alice Springs,
      central Australia over the period January 1995-December 1997. Nine NLV-positive
      cases were identified amongst stools from 360 different patients. From the nine
      cases however, eight different NLV strains were identified from comparisons of
      the sequence of a section of the RNA polymerase gene, and a high degree of
      genomic diversity was evident amongst them. In general, these strains were more
      similar to those identified in other countries than to those identified in
      central Australia over the three year period. Of the strains identified, six (and
      most probably seven) were classified in genogroup I, while only one was
      classified in genogroup II. This predominance of genogroup I strains is in
      contrast to most of the more recent findings made elsewhere, including those made
      in other parts of Australia. Phylogenetic analysis indicated that the central
      Australian strains spanned a range of known representative NLV strains, with one
      of the genogroup I strains showing a 96% nucleotide identity to Saratoga virus.

PMID- 11252673
TI  - Rotavirus infections.
AB  - In 1976, John Rohde, highlighting the importance of diarrhea as prime killer of
      children in the developing world, beckoned the scientific community to "take
      science where the diarrhea is". The World Health Organization estimates that one
      billion diarrheal episodes occur in infants annually resulting in 3.3 million
      deaths, making diarrheal disease a major contributor to infant mortality in
      developing world (Bern et al., 1992). The need for simple, effective and
      inexpensive intervention to treat diarrhea and to prevent its occurrence is
      urgent and abundantly clear. Among the etiological agents of acute infectious
      diarrhea rotaviruses account for nearly 25% of hospital admissions in India with
      vomitting and diarrhea followed by severe dehydration in very young children
      below 2 years of age (Broor et al., 1985). In developing countries, it has been
      estimated that more than 870,000 children die from rotavirus infection every year
      (Perez-Schael, 1996). The discovery of rotavirus by Bishop and colleagues in 1973
      initiated a line of research that has progressed rapidly towards the goal of
      prevention of rotavirus diarrhea (Bishop et al., 1973).

PMID- 11252674
TI  - Molecular mechanisms of replication of herpes simplex virus 1.
AB  - The present review focuses on recent development in our understanding of the
      molecular mechanisms of DNA replication of herpes simplex virus 1 (HSV-1).
      Progress made in the characterization of the early events of viral DNA synthesis
      and of virus-host cell interactions, especially in the context with the formation
      of viral DNA replication sites, is highlighted. An up-dated overview is presented
      on important stages of lytic infection cycle, such as virion entry, viral DNA
      synthesis, viral DNA cleavage and packaging into preformed capsids; and
      maturation (nucleocapsid envelopment) and egress of virions. Many novel
      interactions are discussed that extend not only our knowledge of the biology of
      this virus but may represent possible new targets for antiherpesviral therapy.

PMID- 11252675
TI  - New products from alkali fusion of ginkgolides A and B.
AB  - Alkali fusion of ginkgolides A and B has afforded five unexpected products 3-7.
      Their structures were established from their spectral data and chemical
      reactions. They were evaluated for their in vitro activity to inhibit the
      platelet-activating factor-induced aggregation of rabbit platelets and show less
      potency than ginkgolides A and B.

PMID- 11252676
TI  - Synthesis of 1,7-bis(4-hydroxypenyl)-4-hydroxy-1,3-heptadiene-5-one, an
      antiplatelet diarylheptanoid from Alpinia blepharocalyx K. schum.
AB  - A general and staight forward total synthesis of 1,7-bis(4-hydroxyphenyl)-3
      hydroxy-1,3-heptadiene-5-one (5) starting from 4-methoxycinnamic acid (6) via
      ethyl 5-(4-methoxyphenyl)-3-hydroxy-2.4-pentadienoate (14) was accomplished in
      19% overall yield.

PMID- 11252677
TI  - A novel neuronal cell protecting substance mescengricin produced by Streptomyces
      griseoflavus.
AB  - Neuronal cell death in brain ischemia reperfusion injury such as stroke was
      induced by L-glutamate toxicity (Choi, D.W. J. Neurosci. 1990. 10, 2493 2501;
      Coyle, J.T. and Puttfarcken, P. Science 1993, 262, 689 695). In the course of our
      screening for neuronal cell protecting substances of microbial origin, we
      isolated a novel compound designated mescengricin from Streptomyces griseoflavus
      2853-SVS4(Kim, J.-S., Shin-ya, K., Furihata, K., Hayakawa, Y. and Seto, H.
      Tetrahedron Lett. 1997. 38, 3431 3434). The structure of mescengricin was
      determined by a variety of NMR experiments such as HMBC, D-HMBC (Furihata, K.,
      Seto, H. Tetrahedron Lett. 1995. 36, 2817 2820), 1H 15N HMBC (15N-HMBC). It
      possesses an alpha-carboline structure substituted by a glycerol-ester and a
      hydroxydihydropyrone. Mescengricin protected chick primary mesencephalic neurons
      from L-glutamate toxicity with EC50 value 6.0 nM.

PMID- 11252678
TI  - Blood-pressure lowering, positive chronotropy and inotropy by the Veratrum
      alkaloids germidine and germerine but negative chronotropy by veratridine in
      mice.
AB  - Germidine and germerine, the Veratrum alkaloids lowered blood pressure
      accompanied with positive chronotropy and inotropy in mice. Germerine was more
      potent than germidine in both blood-pressure lowering and positive inotropy,
      whereas veratridine produced negative chronotropy and positive inotropy. An acyl
      group (an acetyl or a 2-methylbutyroyl group) at 3-O-R1 position and a 2
      methylbutyroyl group at 15-O-R2 position in germine were important to produce the
      positive inotropy and chronotropy. The presence of a veratroyl group at 3-O-R1
      position and a free hydroxyl group at 15-O-R2 position may be essential to
      produce the negative chronotropy by veratridine. The positive inotropy by
      germidine and veratridine may be due to TTX-resistant Na+ channel activation.

PMID- 11252679
TI  - Salvianolic acid B protects the memory functions against transient cerebral
      ischemia in mice.
AB  - The objective of this work was to study the protective effects of salvianolic
      acid B (Sal B) on the dysfunctions of learning and memory induced by transient
      cerebral ischemia in mice. The mechanisms of its actions also were researched
      both in vivo and in vitro. The model of dysfunction of learning and memory
      induced by transient cerebral ischemia in mice was used. One trail passive
      avoidance tests were used to evaluate the learning and memory functions and
      experiments in vitro were employed to observe the antioxidative effects of Sal B.
      Cerebral transient ischemia would impair the function of memory in mice. In step
      down test. the error number and latency were 2.63 and 120.5 in control group and
      were 1.35 and 234.4 respectively in sham operated group (p < 0.05). In Sal B
      treated groups, the error number was less and latency was longer significantly
      than those of control group. Meanwhile. 3 and 10 mgkg(-1) of Sal B iv. reduced
      the malondialdehyde contents in cortex, hippocampus and striatum of cerebral
      transient ischemia rat ion vivo. Sal B 10--100 nmol L(-1) also inhibited lipid
      peroxidation and scavenged free hydroxyl radicals in vitro. As conclusion. Sal B
      ameliorated learning and memory dysfunctions induced by cerebral transient
      ischemia. Its actions might be related to its antioxidant activity.

PMID- 11252680
TI  - Synthesis of (+)-lariciresinol 3a-acetate, a lignan from Aglaia elaeagnoidea.
AB  - (+)-Lariciresinol 3a-acetate [(+)-(3S)-acetyloxymethyl-(2S)-(4-hydroxy-3
      methoxyphenyl)-(4R)-[(4-hydroxy-3-methoxyphenyl)methyl]tetrahydrofuran] (1), a
      metabolite of A. elaeagnoidea was synthesized starting from (-)-lariciresinol (2)
      in three steps with an overall yield of 66%.

PMID- 11252681
TI  - Synthesis of N-[3,4-dimethoxyphenyl)propanoyl]pyrrole, a metabolite of Piper
      brachystachyum.
AB  - N-[3-(3,4-Dimethoxyphenyl)propanoyl]pyrrole (1) has been synthesized in three
      steps starting from veratraldehyde (2) with an overall yield of 66%.

PMID- 11252682
TI  - A new triterpenoid from Stelmatocrypton khasianum.
AB  - A new triterpenoid, 2alpha-,3beta,-,19alpha-trihydroxy-urs-12-ene-24,28-dioic
      acid (1), along with two known compounds. 3beta-acetoxy-urs-12-ene-11-one (2) and
      vomifoliol (3), was isolated from stems of Stelmatocryprton khasianum for the
      first time. Their structures were elucidated on the basis of chemical and
      spectroscopic methods.

PMID- 11252683
TI  - Alcyonacean metabolites VII--chemical constituents of Lobophytum denticulatum and
      Lobophytum strictum of the Indian Ocean.
AB  - A rare cembranoid diterpene, (7E,11E.1 R,2S,3R,4R,l4S)-14-acetoxy-3,4-epoxycembra
      7,11,15-triene-17,2-olide (1), was isolated from Lobophytum denticulatum and a
      new polyhydroxysterol, 7-hydroxyandamansterol (9) has been identified as
      peracetyl derivative from Lobophytum strictum. Several known polyhydroxysterols
      have also been isolated from these organisms. 1 exhibited moderate antibacterial
      activity.

PMID- 11252684
TI  - A new cardenolide from the seeds of Terminalia arjuna (W&A).
AB  - A new cardenolide 14,16 dianhydrogitoxigenin-3-beta-D-xylopyranosyl (1 -->2)- O
      beta-D-galactopyranoside was isolated from the ethylacetate soluble fraction of
      the alcoholic extract of the seeds of Terminalia arjuna by various colour
      reactions, chemical degradations and spectral analysis.

PMID- 11252685
TI  - Fasting followed by vegetarian diet in patients with rheumatoid arthritis: a
      systematic review.
AB  - Clinical experience suggests that fasting followed by vegetarian diet may help
      patients with rheumatoid arthritis (RA). We reviewed the available scientific
      evidence, because patients frequently ask for dietary advice, and exclusive
      pharmacological treatment of RA is often not satisfying. Fasting studies in RA
      were searched in MEDLINE and by checking references in relevant reports. The
      results of the controlled studies which reported follow-up data for at least
      three months after fasting were quantitatively pooled. Thirty-one reports of
      fasting studies in patients with RA were found. Only four controlled studies
      investigated the effects of fasting and subsequent diets for at least three
      months. The pooling of these studies showed a statistically and clinically
      significant beneficial long-term effect. Thus, available evidence suggests that
      fasting followed by vegetarian diets might be useful in the treatment of RA. More
      randomised long-term studies are needed to confirm this view by methodologically
      convincing data.

PMID- 11252686
TI  - Celecoxib versus diclofenac in the management of osteoarthritis of the knee.
AB  - OBJECTIVE: A clinical trial was conducted in 600 patients with OA of the knee to
      test the hypothesis that the specific COX-2 inhibitor, celecoxib, has equivalent
      efficacy and a superior tolerability/safety profile when compared to diclofenac,
      the current worldwide standard of care. METHODS: Patients were administered
      celecoxib 100 mg BID, diclofenac 50 mg TID or placebo for 6 weeks in a
      multicentre, double-blind. placebo-controlled trial. RESULTS: Primary efficacy
      measures (index joint pain by VAS, WOMAC index) indicated statistically
      significant improvement versus placebo for both celecoxib and diclofenac and no
      statistically significant differences between celecoxib and diclofenac. American
      Pain Society (APS) measures to assess the rapidity of onset of action showed
      statistically significant and comparable pain relief versus placebo within 24 h
      for both celecoxib and diclofenac. More diclofenac patients reported GI side
      effects than patients treated with either placebo or celecoxib. Diclofenac
      treated patients experienced statistically significant elevations in mean hepatic
      transaminases and serum creatinine and reductions in haemoglobin concentration
      when compared to placebo, events not observed with celecoxib. CONCLUSION:
      Celecoxib 200 mg daily is as effective as diclofenac 150 mg daily for relieving
      signs and symptoms of OA of the knee, including pain, and has a rapid onset of
      action. However, celecoxib appears to have a superior safety and tolerability
      profile.

PMID- 11252687
TI  - Tolerability profiles of rofecoxib (Vioxx) and Arthrotec. A comparison of six
      weeks treatment in patients with osteoarthritis.
AB  - OBJECTIVE: To compare the incidence of selected spontaneously reported adverse
      events (AEs) in patients with osteoarthritis (OA) treated with rofecoxib (VIOXX,
      12.5 mg qd) or Arthrotec (diclofenac 50 mg/misoprostol 200 mcg bid). METHODS:
      Double-blind, parallel-group, 6-week study of patients aged > or = 40 years with
      a clinical diagnosis of OA treated with rofecoxib or Arthrotec. Primary endpoint:
      self-reported diarrhea; secondary endpoints: abdominal pain, discontinuations due
      to AEs, GI AEs and NSAID-type GI AEs (ie., acid reflux, dyspepsia, epigastric
      discomfort, heartburn, nausea, vomiting). RESULTS: Among 483 patients (80.3%
      females, mean age 62.1), the rofecoxib group vs the Arthrotec group respectively
      reported diarrhea 6.2% vs 16.2% (p<0.001); drug-related diarrhea 3.7% vs 16.2%
      (p<0.001); one or more clinical AEs 52.9% vs 73.0% (p<0.001); GI AEs 28.9% vs
      48.5% (p<0.001); NSAID-type GI AEs 18.6% vs 29.9% (p=0.004); discontinuations due
      to abdominal pain 0.4% vs 3.7% (p<0.05); and discontinuations due to any AE 4.1%
      vs 9.1% (p=0.029). No significant differences were observed in efficacy.
      CONCLUSION: Rofecoxib 12.5 mg qd has improved GI tolerability and similar
      efficacy compared to Arthrotec (diclofenac 50 mg/misoprostol 200 mcg bid).

PMID- 11252688
TI  - Effects of sulfasalazine treatment on serum immunoglobulin levels in children
      with juvenile chronic arthritis.
AB  - This article describes the effects of sulfasalazine (SSZ) treatment on serum
      immunoglobulin (Ig) levels in 6 children with oligoarticular- or polyarticular
      onset juvenile chronic arthritis (JCA). None of the children who developed
      dysimmunoglobulinemia during treatment showed clinical symptoms of this adverse
      event, in particular none developed severe infections. All patients regained
      normal immunoglobulin levels after discontinuing SSZ treatment. One patient with
      a partial IgA deficiency at the start of SSZ treatment showed a slow increase in
      the IgA level during treatment. During follow-up (4-6 years), one patient
      spontaneously developed a dysimmunoglobulinemia and one patient developed
      diabetes mellitus. Based on these case reports and review of the literature we
      advocate monitoring of serum immunoglobulin levels while on SSZ treatment.

PMID- 11252689
TI  - Eighteen years follow-up study of the clinical manifestations and progression of
      Dupuytren's disease.
AB  - OBJECTIVE: To evaluate the clinical manifestations and progression of Dupuytren's
      disease. METHODS: In 1981-82 a total of 1297 men were examined for Dupuytren's
      disease, and of these 19.2% had the disease. In 1999 those with signs of the
      disease in 1981-82 were invited for a follow-up study. As controls symptom free
      individuals from the study in 1981-82 were invited. RESULTS: A total of 53
      individuals from the control group had developed Dupuytren's disease in 1999. Men
      with palmar nodules/fibrous cord in 1981-82 were more likely to develop
      contracted fingers than those without Dupuytren's disease. Patients with young
      age at disease onset more often required operations than those with later onset.
      Of the men who had been operated 70% still had finger contractures in 1999.
      CONCLUSION: The incidence of Dupuytren's disease is high in elderly men.
      Dupuytren's disease is progressive in nature and most operated patients have
      recurrent finger contractures.

PMID- 11252690
TI  - An assessment of the new "SCORE" index as a predictor of osteoporosis in women.
AB  - BACKGROUND: The study was done to determine whether the new SCORE (Simple
      Calculated Osteoporosis Risk Estimation) index might reduce the utilization of
      bone mineral density (BMD) measurement. METHODS: 989 consecutive patients who
      were referred by a range of physicians for BMD assessments at one of two clinics
      had a SCORE index constructed. Approximately 95% of the subjects were Caucasian.
      The index is based on only 6 factors: age, previous fractures, rheumatoid
      arthritis, estrogen use, weight, and race. RESULTS: All but 1 (0.1%) of those
      with a femoral neck BMD T-score of < -2.5 had an abnormal SCORE index. However,
      its specificity was relatively low, since two thirds of those individuals also
      with an abnormal index had a T-score of > -2.5. One percent false negatives were
      also seen in the lumbar spine. CONCLUSION: The SCORE index correctly predicted
      those individuals who did not have an osteoporotic T-score. It was of the most
      value in the < 60 age group. DISCUSSION: The precise role of BMD measurement in
      the assessment and management of individuals possibly at risk for osteoporosis
      remains controversial. Our results suggest that the prior use of the SCORE index
      by the referring physicians to screen the patients sent for BMD measurement would
      have allowed them to exclude over 20% of the patients referred for assessment,
      and therefore reduce the need and cost of BMD measurement. The proportion of
      individuals who had a normal SCORE index, and would have been screened out, was
      43% in the under 60 year age group, but in the 65 and over age group it provided
      no additional information to help with, for example, the National Osteoporosis
      Foundation (NOF) guidelines.

PMID- 11252691
TI  - Cancer polyarthritis resembling rheumatoid arthritis as a first sign of hidden
      neoplasms. Report of two cases and review of the literature.
AB  - Recent onset arthritis reminiscent of rheumatoid arthritis (RA) may be an early
      manifestation of an occult malignancy. In this report, we present two patients
      with cancer-associated polyarthritis. Both suffered from symmetric polyarthritis
      when initially visiting their physicians and did not achieve relief when treated
      with non-steroidal anti-rheumatic drugs (NSAIDs). In both patients, subsequent
      work-up led to the diagnosis of an underlying malignancy. One patient suffered
      from small cell lung cancer (SCLC), while the other was diagnosed with
      adenocarcinoma of the colon. In both, the arthritis spontaneously disappeared
      after successful treatment of the malignancy, i.e. chemotherapy and tumor
      resection, respectively. We discuss these cases in view of the existing
      literature, since awareness of the entity of cancer polyarthritis is necessary
      for its timely treatment and may potentially be life-saving.

PMID- 11252692
TI  - Sensorineural hearing loss in conjunction with aortic insufficiency in systemic
      lupus erythematosus.
AB  - Sensorineural hearing loss may occur in SLE, but aortic insufficiency has been
      very rarely reported. We are describing two patients with well-established SLE
      who developed bilateral hearing loss and aortic insufficiency, associated with
      serological evidence of active lupus. Neither patient had evidence of keratitis,
      and thus did not satisfy criteria for Cogan's syndrome. The aortic insufficiency
      in one patient stabilized after treatment with high doses of steroids while in
      the second patient, who refused medical treatment, it progressed requiring
      surgical valve replacement. Our observations suggest that the aortic valve and
      the inner ear may share some antigenic crossreactivity not shared by the cornea.
      In SLE patients, with sensorineural hearing loss, echocardiography should be
      performed looking for evidence of aortic insufficiency, which may be steroid
      responsive.

PMID- 11252693
TI  - Vasculitis of the internal carotid artery in Wegener's granulomatosis: comparison
      of ultrasonography, angiography, and MRI.
AB  - A 37-year old male with newly diagnosed, untreated Wegener's granulomatosis
      including glomerulonephritis, sinusitis, conjunctivitis, arthralgias, and
      positive cANCA, developed a pulsating tumor in the left submandibular region and
      a reversible ischemic neurologic deficit. Ultrasonography revealed both a
      hyperechoic wall thickening of the left proximal internal carotid artery as is
      known in Takayasu's arteritis and a surrounding hypoechoic region typical for
      perivasculitis. The wall thickening and the perivascular infiltrate could be less
      clearly seen by MRI. Ultrasonography, angiography, and MRI demonstrated a 3 cm
      long, 30%, stenosis. Angiography and MRI additionally found a more distally
      located kinking of the internal carotid artery that was missed by
      ultrasonography. Carotid artery vasculitis is a rare complication of Wegener's
      granulomatosis. In this case ultrasonography was superior to angiography and MRI
      to visualize the artery wall and the surrounding tissue, but it failed to
      evaluate the whole distance of the vessel.

PMID- 11252694
TI  - HLA-B27 subtypes in Croatian patients with ankylosing spondylitis.

PMID- 11252695
TI  - Acute mountain sickness; prophylactic benefits of antioxidant vitamin
      supplementation at high altitude.
AB  - Acute mountain sickness; prophylactic benefits of Free-radical-mediated damage to
      the blood-brain barrier may be implicated in the pathophysiology of acute
      mountain sickness (AMS). To indirectly examine this, we conducted a randomized
      double-blind placebo-controlled trial to assess the potentially prophylactic
      benefits of enteral antioxidant vitamin supplementation during ascent to high
      altitude. Eighteen subjects aged 35 +/- 10 years old were randomly assigned
      double-blind to either an antioxidant (n = 9) or placebo group (n = 9). The
      antioxidant group ingested 4 capsules/day(-1) (2 after breakfast/2 after evening
      meal) that each contained 250 mg of L-ascorbic acid, 100 IU of dl-a-tocopherol
      acetate and 150 mg of alpha-lipoic acid. The placebo group ingested 4 capsules of
      identical external appearance, taste, and smell. Supplementation was enforced for
      3 weeks at sea level and during a 10-day ascent to Mt. Everest base camp
      (approximately 5,180 m). Antioxidant supplementation resulted in a comparatively
      lower Lake Louise AMS score at high altitude relative to the placebo group (2.8
      +/- 0.8 points versus 4.0 +/- 0.4 points, P = 0.036), higher resting arterial
      oxygen saturation (89 +/- 5% versus 85 +/- 5%, P = 0.042), and total caloric
      intake (13.2 +/- 0.6 MJ/day(-1) versus 10.1 +/- 0.7 MJ/day(-1), P = 0.001); the
      latter is attributable to a lower satiety rating following a standardized meal.
      These findings indicate that the exogenous provision of water and lipid-soluble
      antioxidant vitamins at the prescribed doses is an apparently safe and
      potentially effective intervention that can attenuate AMS and improve the
      physiological profile of mountaineers at high altitude.

PMID- 11252696
TI  - Dermatoglyphics of a high altitude Peruvian population and interpopulation
      comparisons.
AB  - Studies of genetic structures of Andean human populations have not been numerous,
      even though these studies could be used to answer questions concerning migration
      routes of the indigenous peoples who populated America. Such studies could
      provide basic genetic information and clarify uncertainties surrounding genetic
      relatedness of South American indigenous peoples. This present work describes,
      quantifies, and analyzes the digital and palmar dermatoglyphics of 120 people in
      the community of San Pedro de Casta, Peru. The results were then compared using
      distance analysis to all other Peruvian population values studied to date and
      other South American populations. The dermatoglyphic indicators studied were the
      distribution of digital pattern frequencies, the total ridge counts (TRC), the
      pattern intensity index (PII), the atd angle, and the a-b ridge counts. The
      results did not show statistically significant differences for digital patterns
      between hands, neither within a sex nor between sexes. The means and standard
      deviations of PII and TRC were 12.32 +/- 3.97 and 112.18 +/- 45.09, respectively.
      The means and standard deviations for the other two indicators were the
      following: atd angle, 94.85 degrees +/- 12.33; and a-b ridge counts, 81.57 +/-
      9.06. The distance analyses results suggest the existence of two different
      genetic lines among high altitude populations, as well as the need for further
      research.

PMID- 11252697
TI  - Peak heart rates at extreme altitudes.
AB  - We have measured maximal heart rate during a graded maximal bicycle exercise test
      to exhaustion in five healthy climbers before and during an expedition to Mt.
      Everest. Maximal heart rates at sea level were 186 (177-204) beats/min(-1) at sea
      level and 170 (169-182) beats/min(-1) with acute hypoxia. After 1, 4 and 6 weeks
      of acclimatization to 5400 m, maximal heart rates were 155 (135-182), 158 (144
      182), and 155 (140-183) beats/min(-1), respectively. Heart rates of two of the
      climbers were measured during their attempt to reach the summit of Mt. Everest
      without the use of supplemental oxygen. The peak heart rates at 8,750 m for the
      two climbers were 142 and 144 beats/min(-1), which were similar to their maximal
      heart rates during exhaustive bicycle exercise at 5,400 m, the values being 144
      and 148 beats/min(-1), respectively. The peak heart rates at 8,750 m are in
      agreement with other field studies, but considerably higher than values reported
      from hypobaric chamber studies.

PMID- 11252698
TI  - Safe upper limits for oxygen enrichment of room air at high altitude.
AB  - Oxygen enrichment of room air at high altitude has been shown to improve mental
      performance, sleep quality, and work capacity. Until now, the usual strategy has
      been to use an oxygen concentration that reduces the equivalent altitude to about
      3,000 m, where the equivalent altitude is that which gives the same inspired PO2
      during air breathing. However, standards adopted by the National Fire Protection
      Association allow considerably higher oxygen concentrations without introducing a
      fire hazard. For example, by raising the oxygen concentration to 31.5% at an
      altitude of 5,000 m, the equivalent altitude can be safely reduced to less than
      2,000 m. At the extreme altitude of 8,000 m, the equivalent altitude can be
      reduced to less than 4,000 m without increasing the fire hazard. These increased
      levels of oxygen enrichment are feasible in practice using oxygen concentrators.
      They may be useful if lowlanders need to ascend rapidly and stay at high
      altitude, or for treating people with high altitude illnesses.

PMID- 11252699
TI  - Reascent following resolution of high altitude pulmonary edema (HAPE).
AB  - There is an absence of information in the literature regarding reascent to high
      altitude following resolution of HAPE (high altitude pulmonary edema). This
      report presents three cases of HAPE that are notable for later reascent to a high
      summit (up to 8,850 m) within the time course of each expedition. These cases
      illustrate that careful, gradual reascent following recovery and acclimatization
      after an episode of HAPE precipitated by rapid ascent may be considered. The
      pathophysiology of HAPE is reviewed with a focus on the evidence for rapid
      reversibility of pulmonary vascular injury. The evidence for protective pulmonary
      vascular remodeling is discussed to further support such a recommendation for
      cases of uncomplicated HAPE.

PMID- 11252700
TI  - The scientific observatories on Mont Blanc.
AB  - Since the first ascent of Mont Blanc by Jacques Balmat and Dr. Michel-Gabriel
      Paccard in 1786, numerous scientific events have taken place on the highest peak
      of Europe. Horace Benedict de Saussure, since his first ascent in 1787, made
      numerous observations on barometric pressure, temperature, geology, and mountain
      sickness on Mont Blanc. Over the next 100 years, scientists and physicians
      climbed Mont Blanc and made many interesting although anecdotal reports. Science
      on Mont Blanc exploded at the end of the 19th century. A major player at that
      time was Joseph Vallot (1854-1925), who constructed an observatory in 1890 at
      4,358 m on the Rochers des Bosses and then moved it in 1898 to a better location
      at 4,350 m. There Vallot and invited scientists made observations over more than
      30 years: studies in geology, glaciology, astronomy, cartography, meteorology,
      botany, physiology and medicine were performed and published in the seven volumes
      of the Annales de l'Observatoire du Mont Blanc, between 1893 and 1917, and in the
      Comptes Rendus de l'Academie des Sciences. While Jules Janssen and Xaver Imfeld
      were preparing the construction of the new observatory on the top of Mont Blanc,
      Dr. Jacottet died in 1891 at the Observatoire Vallot from a disease that was
      clearly attributed by Dr. Egli-Sinclair to the effect of high altitude. This was
      probably the first case of high altitude pulmonary edema documented by an autopsy
      and suspected to be directly due to high altitude. Extensive studies on
      ventilation were made from 1886 to 1900. Increase in ventilation with altitude
      was documented, with the phenomenon of "ventilatory acclimatization." Paul Bert's
      theories on the role of oxygen in acute mountain sickness were confirmed in 1903
      and 1904 by studying the effects of oxygen inhalation. In 1913, Vallot documented
      for the first time the decrease in physical performance at the top of Mont Blanc
      using squirrels. After that pioneering era, few studies were done until 1984,
      when a team of the Association pour la Recherche en Physiologie de
      l'Environnement (ARPE) renovated the observatory and started to organize annual
      scientific expeditions.

PMID- 11252701
TI  - Letter from Dolpa.

PMID- 11252702
TI  - Transient monocular amaurosis at high altitude.

PMID- 11252703
TI  - Lessons from genetic discrimination.

PMID- 11252704
TI  - College women's awareness and consumption of folic acid for the prevention of
      neural tube defects.
AB  - PURPOSE: Awareness and consumption of folic acid in the context of neural tube
      defect prevention among college women were assessed. METHODS: Subjects documented
      folic acid awareness and multivitamin consumption. Beliefs about folic acid
      before and after an educational intervention were characterized using the Health
      Belief Model (HBM) and the Fetal Health Locus of Control Scale (FHLCS). RESULTS:
      Awareness of folic acid was not associated with multivitamin consumption. Belief
      variables were not associated with awareness or consumption of folic acid.
      CONCLUSION: This study does not support educational interventions based on the
      HBM or FHLCS to increase multivitamin consumption among college women.

PMID- 11252705
TI  - Patients' fear of genetic discrimination by health insurers: the impact of legal
      protections.
AB  - PURPOSE: The impact of laws restricting health insurers' use of genetic
      information has been assessed from two main vantage points: (1) whether they
      reduce the extent of genetic discrimination and (2) whether they reduce the fear
      of discrimination and the resulting deterrence to undergo genetic testing. A
      previous report from this study concluded that there are almost no well
      documented cases of health insurers either asking for or using presymptomatic
      genetic test results in their underwriting decisions, either before or after
      these laws, or in states with or without these laws. This report evaluates the
      perceptions and the resulting behavior by patients and clinicians. METHODS: A
      comparative case study analysis was performed in seven states with different laws
      respecting health insurers' use of genetic information (no law, new prohibition,
      mature prohibition). Semistructured interviews were conducted in person with five
      patient advocates and with 30 experienced genetic counselors or medical
      geneticists, most of whom deal with adult-onset disorders. Also, multiple
      informed consent forms and patient information brochures were collected and
      analyzed using qualitative methods. RESULTS: Patients' and clinicians' fear of
      genetic discrimination greatly exceeds reality, at least for health insurance. It
      is uncertain how much this fear actually deters genetic testing. The greatest
      deterrence is to those who do not want to submit the costs of testing for
      reimbursement and who cannot afford to pay for testing. There appears to be
      little deterrence for tests that are more easily affordable or when the need for
      the information is much greater. Fear of discrimination plays virtually no role
      in testing decisions in pediatric or prenatal situations, but is significant for
      adult-onset genetic conditions. CONCLUSION: Existing laws have not greatly
      reduced the fear of discrimination. This may be due, in part, to clinicians' lack
      of confidence that these laws can prevent discrimination until there are test
      cases of actual enforcement. Ironically, there may be so little actual
      discrimination that it may not be possible to initiate good test cases.

PMID- 11252706
TI  - A familial risk profile for osteoporosis.
AB  - PURPOSE: To describe genetic epidemiologic aspects of osteoporosis. METHODS: 69
      patients with osteoporosis were interviewed regarding personal and family
      histories of osteoporosis and related fractures. Family history information was
      obtained on 421 first degree and 748 second degree relatives. RESULTS: 45% of
      cases reported a family history of osteoporosis. Familial cases were
      characterized neither by an earlier age of diagnosis nor by a greater degree of
      phenotypic severity. Empiric risks for osteoporosis were highest for mothers,
      33%, and were 19% for sisters. CONCLUSION: These results provide an initial
      genetic epidemiologic profile for osteoporosis and information useful for genetic
      counseling.

PMID- 11252707
TI  - The gap between practice and genetics education of health professionals: HuGEM
      survey results.
AB  - PURPOSE: To determine the genetics education needs and priorities of dietitians,
      occupational therapists, physical therapists, psychologists, speech-language
      hearing specialists, and social workers. METHODS: A random sample mail survey of
      3,600 members of 6 national health professional organizations was undertaken in
      1998 and resulted in 1,958 responses. RESULTS: A majority worked with clients
      with genetic conditions, most were providing genetic services to some clients,
      few had high confidence in providing genetic services, most had little or no
      education in genetics, and two-thirds wanted continuing education. CONCLUSION:
      The study shows a critical need for genetics education of allied and counseling
      health professionals.

PMID- 11252709
TI  - Fragile X full mutations are more similar in siblings than in unrelated patients:
      further evidence for a familial factor in CGG repeat dynamics.
AB  - PURPOSE: We sought to compare patterns of full mutation repeat-length variability
      in the peripheral blood DNA of patients with fragile X syndrome to determine
      whether siblings possess mutation patterns more similar than those of unrelated
      patients. METHODS: Mutation patterns were visualized by Southern blot analysis
      and captured digitally with a phosphor imager. Novel comparison strategies based
      on overlapping profile plots and calculation of weighted mean CGG repeat values
      were used to assess mutation pattern similarity. RESULTS: Within the population
      that we analyzed of 56 patients with full mutation, mutation patterns were found
      to be more similar in siblings than in unrelated patients. CONCLUSION: These
      results indicate that repeat-length variability may be generated in a nonrandom
      manner and that familial factors influence this process.

PMID- 11252708
TI  - Clinical and molecular studies in a unique family with autosomal dominant limb
      girdle muscular dystrophy and Paget disease of bone.
AB  - PURPOSE: To characterize the clinical features and perform linkage analysis of
      candidate loci in a large Illinois family with autosomal dominant limb-girdle
      muscular dystrophy (LGMD) and Paget disease of bone (PDB). METHODS: The family
      includes 11 affected individuals (8 M, 3 F). Clinical, biochemical and radiologic
      evaluations were performed to delineate clinical features of the disorder.
      Linkage analysis with polymorphic markers was performed for previously identified
      LGMD, PDB and cardiomyopathy loci. RESULTS: Onset of PDB is early, at a mean age
      of 35 y, with classic distribution involving the spine, pelvis, and skull. Muscle
      weakness and atrophy is progressive with mildly elevated to normal creatine
      phosphokinase levels. Muscle biopsy in the oldest male revealed vacuolated
      fibers, however, in others revealed nonspecific myopathy. Affected individuals
      die from progressive muscle weakness, and respiratory and cardiac failure in
      their 40s-60s. Linkage analysis excluded autosomal dominant and recessive LGMD,
      PDB, and cardiomyopathy loci. CONCLUSION: Autosomal dominant LGMD associated with
      PDB is an unusual disorder. Linkage analysis indicates a unique locus in this
      family.

PMID- 11252711
TI  - Some major milestones and future directions.

PMID- 11252710
TI  - Gender verification of female athletes.
AB  - The International Olympic Committee (IOC) officially mandated gender verification
      for female athletes beginning in 1968 and continuing through 1998. The rationale
      was to prevent masquerading males and women with "unfair, male-like" physical
      advantage from competing in female-only events. Visual observation and
      gynecological examination had been tried on a trial basis for two years at some
      competitions leading up to the 1968 Olympic Games, but these invasive and
      demeaning processes were jettisoned in favor of laboratory-based genetic tests.
      Sex chromatin and more recently DNA analyses for Y-specific male material were
      then required of all female athletes immediately preceding IOC-sanctioned
      sporting events, and many other international and national competitions following
      the IOC model. On-site gender verification has since been found to be highly
      discriminatory, and the cause of emotional trauma and social stigmatization for
      many females with problems of intersex who have been screened out from
      competition. Despite compelling evidence for the lack of scientific merit for
      chromosome-based screening for gender, as well as its functional and ethical
      inconsistencies, the IOC persisted in its policy for 30 years. The coauthors of
      this manuscript have worked with some success to rescind this policy through
      educating athletes and sports governors regarding the psychological and physical
      nature of sexual differentiation, and the inequities of genetic sex testing. In
      1990, the International Amateur Athletics Federation (IAAF) called for
      abandonment of required genetic screening of women athletes, and by 1992 had
      adopted a fairer, medically justifiable model for preventing only male
      "impostors" in international track and field. At the recent recommendation of the
      IOC Athletes Commission, the Executive Board of the IOC has finally recognized
      the medical and functional inconsistencies and undue costs of chromosome-based
      methods. In 1999, the IOC ratified the abandonment of on-site genetic screening
      of females at the next Olympic Games in Australia. This article reviews the
      history and rationales for fairness in female-only sports that have led to the
      rise and fall of on-site, chromosome-based gender verification at international
      sporting events.

PMID- 11252712
TI  - Tandem mass spectrometry in newborn screening. American College of Medical
      Genetics/American Society of Human Genetics Test and Technology Transfer
      Committee Working Group.

PMID- 11252713
TI  - They don't care.

PMID- 11252714
TI  - A doorman to keep foreign genes out. A new genetic barrier can protect corn from
      unwanted genetic modification.

PMID- 11252715
TI  - Reaching out. Scientists met in Heidelberg and discussed methods of restoring
      public trust in science.

PMID- 11252716
TI  - Hot nuclei at the Cold Spring. Meeting on 'Dynamic organization of nuclear
      function'.

PMID- 11252717
TI  - The final cut. The importance of tRNA 3'-processing.
AB  - To generate functional tRNA molecules, precursor RNAs must undergo several
      processing steps. While the enzyme that generates the mature tRNA 5'-end, RNase
      P, has been thoroughly investigated, the 3'-processing activity is, despite its
      importance, less understood. While nothing is known about tRNA 3'-processing in
      archaea, the phenomenon has been analysed in detail in bacteria and is known to
      be a multistep process involving several enzymes, including both exo- and
      endonucleases. tRNA 3'-end processing in the eukaryotic nucleus seems to be
      either exonucleolytic or endonucleolytic, depending on the organism analysed,
      whereas in organelles, 3'-end maturation occurs via a single endonucleolytic cut.
      An interesting feature of organellar tRNA 3'-processing is the occurrence of
      overlapping tRNA genes in metazoan mitochondria, which presents a unique
      challenge for the mitochondrial tRNA maturation enzymes, since it requires not
      only the removal but also the addition of nucleotides by an editing reaction.

PMID- 11252718
TI  - A legal and ethical tightrope. Science, ethics and legislation of stem cell
      research.

PMID- 11252719
TI  - Physical association between the histone acetyl transferase CBP and a histone
      methyl transferase.
AB  - CBP (CREB-binding protein) is involved in transcriptional activation by a great
      variety of sequence-specific transcription factors. CBP has been shown to
      activate transcription through its histone acetyl transferase activity.
      Acetylation is a common post-translational modification of nucleosomal histone N
      terminal tails, which generally correlates with transcriptional activation.
      Histone N-terminal tails are also modified by methylation but its functional
      consequences are largely unknown. Here we found that immunoprecipitation of CBP,
      or of the highly related p300, led to the co-immunoprecipitation of a robust
      histone methyl transferase (HMT) activity, indicating that CBP physically
      interacts with an HMT in living cells. The CBP-associated HMT is specific for
      lysines 4 and 9 of histone H3, which are known to be methylated in living cells.
      These results suggest that histone methylation could be involved in
      transcriptional activation. Furthermore, they raise the question of the link
      between histone methylation and acetylation.

PMID- 11252720
TI  - p21cip1 is required for the differentiation of oligodendrocytes independently of
      cell cycle withdrawal.
AB  - Differentiation of most cell types requires both establishment of G1 arrest and
      the induction of a program related to achieving quiescence. We have chosen to
      study the differentiation of oligodendrocyte cells to determine the role of p27
      and p21 in this process. Here we report that both p27 and p21 are required for
      the appropriate differentiation of these cells. p27 is required for proper
      withdrawal from the cell cycle, p21 is not. Instead, p21 is required for the
      establishment of the differentiation program following growth arrest. Similar
      observations were made in vivo. We show that p21-/- cells withdraw from the cell
      cycle similar to wild-type cells; however, early in animal life, the brain is
      hypomyelinated, inferring that the loss of p21 delayed myelination in the
      cerebellum. We found that we could complement or bypass the differentiation
      failure in p21-/- cells with either PD98059, an inhibitor of Mek1, or by
      transducing them with a tat-p16ink4a protein. We concluded that the two cdk
      inhibitors serve non-redundant roles in this program of differentiation, with p27
      being responsible for arrest and p21 having a function in differentiation
      independent of its ability to control exit from the cell cycle.

PMID- 11252721
TI  - Fission yeast Prp4p kinase regulates pre-mRNA splicing by phosphorylating a non
      SR-splicing factor.
AB  - We provide evidence that Prp4p kinase activity is required for pre-mRNA splicing
      in vivo and show that loss of activity impairs G1-S and G2-M progression in the
      cell cycle. Prp4p interacts genetically with the non-SR (serine/arginine)
      splicing factors Prp1p and Prp5p. Bacterially produced Prp1p is phosphorylated by
      Prp4p in vitro. Prp4p and Prp1p also interact in the yeast two-hybrid system. In
      vivo labelling studies using a strain with a mutant allele of the prp4 gene in
      the genetic background indicate a change in phosphorylation of the Prp1p protein.
      These results are consistent with the notion that Prp4p kinase is involved in the
      control of the formation of active spliceosomes, targeting non-SR splicing
      factors.

PMID- 11252724
TI  - Exploring the unknown. The silent revolution of microbiology.

PMID- 11252723
TI  - Colicin A hybrids: a genetic tool for selection of type II secretion-proficient
      Pseudomonas strains.
AB  - The gram-negative bacterium Pseudomonas aeruginosa secretes the majority of its
      extracellular proteins by the type II secretion mechanism, a two-step process
      initiated by translocation of signal peptide-bearing exoproteins across the inner
      membrane. The periplasmic forms are transferred across the outer membrane by a
      machinery consisting of 12 xcp gene products. Although the type II secretion
      machinery is conserved among gram-negative bacteria, interactions between the
      secreted proteins and the machinery are specific. The lack of a selectable
      phenotype has hampered the development of genetic strategies for studying type II
      secretion. We report a novel strategy to identify rare events, such as those that
      allow heterologous secretion or identification of extragenic suppressors
      correcting xcp defects. This is based on creating a host-vector system where the
      non-secretory phenotype is lethal. The original tool we designed is a hybrid
      protein containing elastase and the pore-forming domain of colicin A.

PMID- 11252722
TI  - The orphan nuclear receptor ROR alpha is a negative regulator of the inflammatory
      response.
AB  - Retinoid-related orphan receptor alpha (ROR alpha) (NR1F1) is a member of the
      nuclear receptor superfamily whose biological functions are largely unknown.
      Since staggerer mice, which carry a deletion in the ROR alpha gene, suffer from
      immune abnormalities, we generated an adenovirus encoding ROR alpha1 to
      investigate its potential role in control of the inflammatory response. We
      demonstrated that ROR alpha is expressed in human primary smooth-muscle cells and
      that ectopic expression of ROR alpha1 inhibits TNFalpha-induced IL-6, IL-8 and
      COX-2 expression in these cells. ROR alpha1 negatively interferes with the NF
      kappaB signalling pathway by reducing p65 translocation as demonstrated by
      western blotting, immunostaining and electrophoretic mobility shift assays. This
      action of ROR alpha1 on NF-kappaB is associated with the induction of IkappaB
      alpha, the major inhibitory protein of the NF-kappaB signalling pathway, whose
      expression was found to be transcriptionally upregulated by ROR alpha1 via a ROR
      response element in the IkappaB alpha promoter. Taken together, these data
      identify ROR alpha1 as a potential target in the treatment of chronic
      inflammatory diseases, including atherosclerosis and rheumatoid arthritis.

PMID- 11252726
TI  - Constitutively active mutants of 5-HT4 receptors are they in unique active
      states?
AB  - Somatic mutations leading to constitutively active G-protein coupled receptors
      (GPCRs) are responsible for certain human diseases. A consistent structural
      description of the molecular change underlying the conversion of GPCRs from an
      inactive R state to an active R* state is lacking. Here, we show that a series of
      constitutively active 5-HT4 receptors (mutated or truncated in the C-terminal and
      the third intracellular loop) were characterized by an increase in their
      denaturation rate at 55 degrees C. The thermal denaturation kinetics were
      monophasic, suggesting that we were measuring mainly the denaturation rate of R*.
      Analysis of these kinetics revealed that constitutively active C-terminal domain
      mutants, were due to a change in the J constant governing the R/R* equilibrium.
      However, the constitutive activity of the receptor mutated within the third
      intracellular loop was the result of both a change in the allosteric J constant
      and a change in the R* conformation.

PMID- 11252728
TI  - Where are they now? A survey of the career possibilities for young scientists in
      the life sciences.

PMID- 11252725
TI  - Domain fusion between SNF1-related kinase subunits during plant evolution.
AB  - Members of the conserved SNF1/AMP-activated protein kinase (AMPK) family regulate
      cellular responses to environmental and nutritional stress in eukaryotes. Yeast
      SNF1 and animal AMPKs form a complex with regulatory SNF4/AMPKgamma and
      SIP1/SIP2/GAL83/AMPKbeta subunits. The beta-subunits function as target selective
      adaptors that anchor the catalytic kinase and regulator SNF4/gamma-subunits to
      their kinase association (KIS) and association with the SNF1 complex (ASC)
      domains. Here we demonstrate that plant SNF1-related protein kinases (SnRKs)
      interact with an adaptor-regulator protein, AKINbetagamma, in which an N-terminal
      KIS domain characteristic of beta-subunits is fused with a C-terminal region
      related to the SNF4/AMPKgamma proteins. AKINbetagamma is constitutively expressed
      in plants, suppresses the yeast delta snf4 mutation, and shows glucose-regulated
      interaction with the Arabidopsis SnRK, AKIN11. Our results suggest that evolution
      of AKINbetagamma reflects a unique function of SNF1-related protein kinases in
      plant glucose and stress signalling.

PMID- 11252729
TI  - Malignant lymphoma presenting as a large mass in the anterior chest wall.
AB  - In general, the preferred treatment for malignant lymphoma is the cytotoxic
      chemotherapy. However, the surgical intervention is often required for diagnosis
      and treatment in cases where the diagnosis is not obvious. In well-chosen cases
      the surgical treatment can contribute importantly to a good outcome and quality
      of life even in malignant lymphoma. We report a rare case of non-Hodgkin's
      lymphoma presenting as a large, rapidly growing mass in the anterior chest wall;
      resection was the key initial treatment.

PMID- 11252727
TI  - Regulation of intracellular trafficking of the EGF receptor by Rab5 in the
      absence of phosphatidylinositol 3-kinase activity.
AB  - Rab5 and phosphatidylinositol 3-kinase (PI3K) have been proposed to co-regulate
      receptor endocytosis by controlling early endosome fusion. However, in this
      report we demonstrate that inhibition of epidermal growth factor (EGF)-stimulated
      PI3K activity by expression of the kinase-deficient PI3K p110 subunit (p110delta
      kin) does not block the lysosomal targeting and degradation of the EGF receptor
      (EGFR). Moreover, inhibition of total PI3K activity by wortmannin or LY294002
      significantly enlarges EGFR-containing endosomes and dissociates the early
      endosomal autoantigen EEA1 from membrane fractions. However, this does not block
      the lysosomal targeting and degradation of EGFR. In contrast, transfection of
      cells with mutant Rab5 S34N or microinjection of anti-Rabaptin5 antibodies
      inhibits EGFR endocytosis. Our results, therefore, demonstrate that PI3K is not
      universally required for the regulation of receptor intracellular trafficking.
      The present work suggests that the intracellular trafficking of EGFR is
      controlled by a novel endosome fusion pathway that is regulated by Rab5 in the
      absence of PI3K, rather than by the previously defined endosome fusion pathway
      that is co-regulated by Rab5 and PI3K.

PMID- 11252730
TI  - Use of A heparin-coated circuit for extracorporeal circulation with selective
      cerebral perfusion.
AB  - The use of selective cerebral perfusion with a heparin-coated extracorporeal
      circuit has not been reported. We developed a unique extracorporeal circulation
      system that can be used for selective cerebral perfusion based on an existing
      heparin-coated circuit with a centrifugal pump for general open-heart surgery and
      a heparin-coated oxygenator without venous drainage by gravity. Between July 1994
      and December 1999, this system was used for 12 patients undergoing surgery for
      true aortic arch aneurysm. The dose of heparin used was reduced to maintain
      minimum activated clotting time above 300 sec during extracorporeal circulation.
      One patient suffered a stroke, and one patient had transient postoperative
      neurologic deficit. One patient died suddenly of ventricular arrhythmia on the
      11th postoperative day. The circuit remained thrombus-free. Selective cerebral
      perfusion with a heparin-coated bypass circuit was safe and very easy to perform
      after a simple modification of a standard circuit for open-heart surgery.

PMID- 11252731
TI  - Thoracic esophageal cancer recurred later than 2 years after esophagectomy with
      extended lymphadenectomy.
AB  - PURPOSE: Although the majority of recurrence was found in 2 years after
      esophagectomy, esophageal cancer could recur lately. To find efficient follow up,
      the patients were compared by periods of recurrence detected. SUBJECTS AND
      METHODS: Esophagectomized 227 patients were subjected. Median follow up period
      was 1289 days. The disease recurred in 84 patients (Group A) in 2 years after
      surgery and in 17 (Group B) lately. Clinicopathological factors were compared
      between these 2 groups. RESULTS: There was no difference in background and
      clinicopathological factors, except Group A was at significantly advanced stage
      than B. The most common pattern of recurrence was hematogeneous in Group A,
      whereas lymphatic in Group B, which was significantly different. In Group B,
      survival rate of patients detected by lymphatic recurrence, which responded to
      radiation, was higher than that detected by hematogeneous one. CONCLUSION: To
      prolong survival, the patients should be carefully followed up later than 2 years
      after surgery with regard for lymphatic recurrence.

PMID- 11252732
TI  - Development of the insulin-like growth factor-I assay system.
AB  - A high speed full automatic ELISA system for measurement of insulin-like growth
      factor-I (IGF-I) was established by using magnetic particle-linked monoclonal
      antibody and enzyme-labeled monoclonal antibody. A standard curve was obtained,
      and the effect of dilution on the assay system was investigated. An IGF-I spike
      recovery test of human serum samples and a study of the correlation with a
      radioimmunoassay system were performed, and good results were obtained from all
      studies. The assay range was 0.5-50 ng/ml, and the time required for the full
      automatic measurement was 15 minutes. This assay system will play a central role
      in the clinical approach to IGF-I.

PMID- 11252733
TI  - Callotasis for post-traumatic shortening and deformity of leg.
AB  - We have been performed callotasis, including hemicallotasis, in cases of more
      than 30 mm limb lengthening and more than 15 degrees angular deformity. There
      were 21 cases in this series. The mean age was 29.8 years old. Ilizarov external
      fixator (EF) was used in 13 cases and Orthofix EF in 8. The operation site was
      femur in 12 cases and tibia in 9 cases. Pre-existed complications were noted to
      occur in 10 cases. Callotasis was indicated in 17 cases, and the average length
      gain was 28.4 mm. Hemicallotasis was indicated in 5 cases, and the mean degree of
      correction angle was 18 degrees. Among available types of EF, Orthofix EF was
      suitable for proximal femoral callotasis, while Ilizarov EF was suitable for
      corrective deformity using hemicallotasis and tibial callotasis. The bone healing
      process of callotsis was better in the absence than presence of pre-existed
      complication. Also, we performed bone transportation using Ilizarov EF in cases
      of pseudoarthrosis with leg shortening and in all cases where bone grafting was
      unnecessary.

PMID- 11252734
TI  - Chondroma within the flexor tendon sheath of the index finger: case report.
AB  - Chondroma of soft tissue is rare. We report a patient in whom a chondroma
      occurred within the flexor tendon sheath of the index finger. Magnetic resonance
      imaging showed the extent of the tumor, which wrapped around flexor tendons
      within the sheath, but did not invade either tendons or sheath. Total excision
      was done with preservation of the flexors and flexor tendon sheath. After the
      operation, the index finger had a full range of motion, and movement was
      painless.

PMID- 11252735
TI  - Left-sided gallbladder associated with anomalous branching of the portal vein
      detected by sonography.
AB  - We experienced a patient with a left-sided gallbladder associated with a right
      umbilical portion. The etiology of the left-sided gallbladder associated with a
      right umbilcal portion was in this case not anomalous positioning of the
      gallbladder, but an embryologic abnormality of the umbilical vein. Ramification
      of the portal vein should be examined in patients with left-sided gallbladder,
      especially those scheduled to undergo hepato-biliary surgery, since
      misunderstanding of anatomy may result in serious problems.

PMID- 11252737
TI  - Same rates for neighbours.

PMID- 11252736
TI  - Portal vein stenting to treat portal vein tumor thrombus in hepatocellular
      carcinoma.
AB  - Tumor thrombus in the portal vein is refractory to therapy and a serious negative
      prognostic factor in hepatocellular carcinoma. We describe herein the case of a
      patient in whom an expandable metallic stent was successfully employed to treat
      portal vein tumor thrombus by restoring blood flow. An expandable metallic stent
      was implanted in a patient with severe main portal vein stenosis caused by tumor
      thrombus protruding from the left portal vein branch. Immediately after stent
      placement, the stenotic lesion was effectively dilated, the portal blood flow
      restored, and portal hypertension relieved. Angiography, computed tomography, and
      doppler ultrasonography done 2 months after the stent placement revealed
      continued patency of the portal vein. Thus, intraportal placement of an
      expandable metallic stent appears to be an effective treatment for major portal
      vein tumor

PMID- 11252738
TI  - Founding populations: Colombian blend?

PMID- 11252739
TI  - Mining gene expression data.

PMID- 11252740
TI  - If winter comes, will flowers follow?

PMID- 11252742
TI  - New light on night blindness.

PMID- 11252741
TI  - Resisting drugs.

PMID- 11252743
TI  - Headless Hydra get Heady.

PMID- 11252744
TI  - The trouble with smoking.

PMID- 11252745
TI  - It's a guy thing.

PMID- 11252747
TI  - Use of population isolates for mapping complex traits.
AB  - Geneticists have repeatedly turned to population isolates for mapping and cloning
      Mendelian disease genes. Population isolates possess many advantages in this
      regard. Foremost among these is the tendency for affected individuals to share
      ancestral haplotypes derived from a handful of founders. These haplotype
      signatures have guided scientists in the fine mapping of scores of rare disease
      genes. The past successes with Mendelian disorders using population isolates have
      prompted unprecedented interest among medical researchers in both the public and
      private sectors. Despite the obvious genetic and environmental complications,
      geneticists have targeted several population isolates for mapping genes for
      complex diseases.

PMID- 11252748
TI  - Genome gymnastics: unique modes of DNA evolution and processing in ciliates.
AB  - In some ciliates, the DNA sequences of the germline genomes have been profoundly
      modified during evolution, providing unprecedented examples of germline DNA
      malleability. Although the significance of the modifications and malleability is
      unclear, they may reflect the evolution of mechanisms that facilitate evolution.
      Because of the modifications, these ciliates must perform remarkable feats of
      cutting, splicing, rearrangement and elimination of DNA sequences to convert the
      chromosomal DNA in the germline genome (micronuclear genome) into gene-sized DNA
      molecules in the somatic genome (macronuclear genome). How these manipulations of
      DNA are guided and carried out is largely unknown. However, the organization and
      manipulation of ciliate DNA sequences are new phenomena that expand a general
      appreciation for the flexibility of DNA in evolution and development.

PMID- 11252746
TI  - The establishment of Spemann's organizer and patterning of the vertebrate embryo.
AB  - Molecular studies have begun to unravel the sequential cell-cell signalling
      events that establish the dorsal-ventral, or 'back-to-belly', axis of vertebrate
      animals. In Xenopus and zebrafish, these events start with the movement of
      membrane vesicles associated with dorsal determinants. This mediates the
      induction of mesoderm by generating gradients of growth factors. Dorsal mesoderm
      then becomes a signalling centre, the Spemann's organizer, which secretes several
      antagonists of growth-factor signalling. Recent studies have led to new models
      for the regulation of cell-cell signalling during development, which may also
      apply to the homeostasis of adult tissues.

PMID- 11252749
TI  - Mammalian cloning: advances and limitations.
AB  - For many years, researchers cloning mammals experienced little success, but
      recent advances have led to the successful cloning of several mammalian species.
      However, cloning by the transfer of nuclei from adult cells is still a hit-and
      miss procedure, and it is not clear what technical and biological factors
      underlie this. Our understanding of the molecular basis of reprogramming remains
      extremely limited and affects experimental approaches towards increasing the
      success rate of cloning. Given the future practical benefits that cloning can
      offer, the time has come to address what should be done to resolve this problem.

PMID- 11252750
TI  - Iron homeostasis: insights from genetics and animal models.
AB  - Disorders that perturb iron balance are among the most prevalent human diseases,
      but until recently iron transport remained poorly understood. Over the past five
      years, genetic studies of patients with inherited iron homeostasis disorders and
      the analysis of mutant mice, rats and zebrafish have helped to identify several
      important iron-transport proteins. With information being mined from the genomes
      of four species, the study of iron metabolism has benefited enormously from
      positional-cloning efforts. Complementing the genomic strategy, targeted
      mutagenesis in mice has produced new models of human iron diseases. The animal
      models described in this review offer valuable tools for investigating iron
      homeostasis in vivo.

PMID- 11252751
TI  - Using Drosophila as a model insect.
AB  - The fruit fly Drosophila melanogaster has become such a popular model organism
      for studying human disease that it is often described as a little person with
      wings. This view has been strengthened with the sequencing of the Drosophila
      genome and the discovery that 60% of human disease genes have homologues in the
      fruit fly. In this review, I discuss the approach of using Drosophila not only as
      a model for metazoans in general but as a model insect in particular.
      Specifically, I discuss recent work on the use of Drosophila to study the
      transmission of disease by insect vectors and to investigate insecticide function
      and development.

PMID- 11252752
TI  - Patenting human genetic material: refocusing the debate.
AB  - The biotechnology industry has become firmly established over the past twenty
      years and gene patents have played an important part in this phenomenon. However,
      concerns have been raised over the patentability of human genetic material,
      through public protests and international statements, but to little effect. Here
      we discuss some of these concerns, the patent authorities' response to them, and
      ways in which to address these issues and to move the debate forward using
      current legal structures.

PMID- 11252753
TI  - The origins of bioinformatics.
AB  - Bioinformatics is often described as being in its infancy, but computers emerged
      as important tools in molecular biology during the early 1960s. A decade before
      DNA sequencing became feasible, computational biologists focused on the rapidly
      accumulating data from protein biochemistry. Without the benefits of super
      computers or computer networks, these scientists laid important conceptual and
      technical foundations for bioinformatics today.

PMID- 11252754
TI  - Genetic disease since 1945.
AB  - Although hereditary disease has been recognized for centuries, only recently has
      it become the prevailing explanation for numerous human pathologies. Before the
      1970s, physicians saw genetic disease as rare and irrelevant to clinical care.
      But, by the 1990s, genes seemed to be critical factors in virtually all human
      disease. Here I explore some perspectives on how and why this happened, by
      looking at two genetic diseases--familial dysautonomia and phenylketonuria.

PMID- 11252755
TI  - A fall lands close to home.

PMID- 11252756
TI  - Nursing home physician decries 'excessive use' of psychotropics.

PMID- 11252757
TI  - Pigmentation on the legs.

PMID- 11252758
TI  - Osteoporosis. Efficacy and safety of a bisphosphonate dosed once weekly.
AB  - Trabecular and cortical bone is continuously being remodeled at microscopic loci
      called basic multicellular units (BMU). Estrogen deficiency in menopause
      contributes to an increase in osteoclastic resorption and/or a decrease in
      osteoblastic formation, which leads to microscopic bone loss at the BMUs. Drug
      treatments for osteoporosis are intended to inhibit bone resorption, reduce the
      rate of bone turnover, and increase bone mass. The bisphosphonate alendronate was
      recently approved for once-a-week dosing for the prevention and treatment of
      postmenopausal osteoporosis. A 70-mg, once-a-week dose of alendronate has been
      shown to be therapeutically equivalent to the standard daily 10-mg dose.
      Tolerability and safety of weekly dosing appear to be similar to daily dosing.

PMID- 11252760
TI  - Falls and function. How to prevent falls and injuries in patients with impaired
      mobility.
AB  - Older persons, particularly those with compromised health, are at increased risk
      of falls, and these events can significantly affect a person's quality of life.
      Risk factors include age, neurologic and musculoskeletal conditions, decreased
      physical strength, foot disorders, and use of medications or alcohol. When
      evaluating a patient who has fallen, physicians should be on the alert for
      intrinsic pathologies or situational conditions that place an older patient at
      increased risk for these incidents. Physical examination should include
      consideration of postural vital signs, polypharmacy, and sensory decline.
      Performance assessments are excellent tools for observing the status of gait and
      balance. Proper documentation and evaluation of a fall is a key step in
      preventive management.

PMID- 11252759
TI  - Benign prostatic hyperplasia. Patient evaluation and relief of obstructive
      symptoms.
AB  - Benign prostatic hyperplasia (BPH) is a common and highly manageable disorder
      that affects most men at some point after age 50. Although classic BPH symptoms
      mimic those of other genitourinary conditions, several straightforward tools are
      available to aid accurate diagnosis. For patients in whom the condition is
      identified early in its progression, prudent management includes periodic
      assessment of disease progression, pharmacotherapy, and phytotherapy. Some
      patients presenting with BPH may require or request surgical intervention and
      several minimally invasive procedures are available, although outcomes and
      complication rates vary for each.

PMID- 11252761
TI  - Blood pressure dysregulation syndrome. The case for control throughout the
      circadian cycle.
AB  - Blood pressure dysregulation syndrome is characterized by abnormal swings in
      blood pressure following postural changes, meals, exercise, and during sleep.
      Although the syndrome may occur in normotensive individuals, a growing body of
      evidence suggests an association between blood pressure dysregulation and
      hypertension. Diagnosis can be aided using 24-hour ambulatory blood pressure
      monitoring. Improved understanding of the syndrome and heightened awareness of
      its existence in older persons can help clinicians provide more effective
      management of hypertension. Adequate control of blood pressure throughout the
      circadian cycle should be a treatment objective.

PMID- 11252762
TI  - Neurosyphilis. Screening does sometimes reveal an infectious cause of dementia.

PMID- 11252763
TI  - Telemedicine for the Medicare population.

PMID- 11252764
TI  - Is heterosynaptic modulation essential for stabilizing Hebbian plasticity and
      memory?
AB  - In 1894, Ramon y Cajal first proposed that memory is stored as an anatomical
      change in the strength of neuronal connections. For the following 60 years,
      little evidence was recruited in support of this idea. This situation changed in
      the middle of the twentieth century with the development of cellular techniques
      for the study of synaptic connections and the emergence of new formulations of
      synaptic plasticity that redefined Ramon y Cajal's idea, making it more suitable
      for testing. These formulations defined two categories of plasticity, referred to
      as homosynaptic or Hebbian activity-dependent, and heterosynaptic or modulatory
      input-dependent. Here we suggest that Hebbian mechanisms are used primarily for
      learning and for short-term memory but often cannot, by themselves, recruit the
      events required to maintain a long-term memory. In contrast, heterosynaptic
      plasticity commonly recruits long-term memory mechanisms that lead to
      transcription and to synpatic growth. When jointly recruited, homosynaptic
      mechanisms assure that learning is effectively established and heterosynaptic
      mechanisms ensure that memory is maintained.

PMID- 11252765
TI  - Neuronal KCNQ potassium channels: physiology and role in disease.
AB  - Humans have over 70 potassium channel genes, but only some of these have been
      linked to disease. In this respect, the KCNQ family of potassium channels is
      exceptional: mutations in four out of five KCNQ genes underlie diseases including
      cardiac arrhythmias, deafness and epilepsy. These disorders illustrate the
      different physiological functions of KCNQ channels, and provide a model for the
      study of the 'safety margin' that separates normal from pathological levels of
      channel expression. In addition, several KCNQ isoforms can associate to form
      heteromeric channels that underlie the M-current, an important regulator of
      neuronal excitability.

PMID- 11252766
TI  - Auditory feedback in learning and maintenance of vocal behaviour.
AB  - Songbirds are one of the best-studied examples of vocal learners. Learning of
      both human speech and birdsong depends on hearing. Once learned, adult song in
      many species remains unchanging, suggesting a reduced influence of sensory
      experience. Recent studies have revealed, however, that adult song is not always
      stable, extending our understanding of the mechanisms involved in song
      maintenance, and their similarity to those active during song learning. Here we
      review some of the processes that contribute to song learning and production,
      with an emphasis on the role of auditory feedback. We then consider some of the
      possible neural substrates involved in these processes, particularly basal
      ganglia circuitry. Although a thorough treatment of human speech is beyond the
      scope of this article, we point out similarities between speech and song
      learning, and ways in which studies of these disparate behaviours complement each
      other in developing an understanding of general principles that contribute to
      learning and maintenance of vocal behaviour.

PMID- 11252767
TI  - A cortical-hippocampal system for declarative memory.
AB  - Recent neurobiological studies have begun to reveal the cognitive and neural
      coding mechanisms that underlie declarative memory--our ability to recollect
      everyday events and factual knowledge. These studies indicate that the critical
      circuitry involves bidirectional connections between the neocortex, the
      parahippocampal region and the hippocampus. Each of these areas makes a unique
      contribution to memory processing. Widespread high-order neocortical areas
      provide dedicated processors for perceptual, motor or cognitive information that
      is influenced by other components of the system. The parahippocampal region
      mediates convergence of this information and extends the persistence of
      neocortical memory representations. The hippocampus encodes the sequences of
      places and events that compose episodic memories, and links them together through
      their common elements. Here I describe how these mechanisms work together to
      create and re-create fully networked representations of previous experiences and
      knowledge about the world.

PMID- 11252768
TI  - Apolipoprotein E receptors: linking brain development and Alzheimer's disease.
AB  - Alzheimer's disease is a debilitating neurodegenerative disorder that afflicts an
      increasing part of our ageing population. An isoform of apolipoprotein E, a
      protein that mediates the transport of lipids and cholesterol in the circulatory
      system, predisposes carriers of this allele to the common late-onset form of the
      disease. How this protein is related to a neurodegenerative disorder is an
      enigma. Mounting evidence indicates that apolipoprotein E receptors, which are
      abundantly expressed in most neurons in the central nervous system, also fulfill
      critical functions during brain development and may profoundly influence the
      pathogenesis of Alzheimer's disease.

PMID- 11252769
TI  - The prefrontal cortex and cognitive control.
AB  - One of the enduring mysteries of brain function concerns the process of cognitive
      control. How does complex and seemingly willful behaviour emerge from
      interactions between millions of neurons? This has long been suspected to depend
      on the prefrontal cortex--the neocortex at the anterior end of the brain--but now
      we are beginning to uncover its neural basis. Nearly all intended behaviour is
      learned and so depends on a cognitive system that can acquire and implement the
      'rules of the game' needed to achieve a given goal in a given situation. Studies
      indicate that the prefrontal cortex is central in this process. It provides an
      infrastructure for synthesizing a diverse range of information that lays the
      foundation for the complex forms of behaviour observed in primates.

PMID- 11252770
TI  - Neurogenesis in the adult brain: death of a dogma.
AB  - For over 100 years a central assumption in the field of neuroscience has been
      that new neurons are not added to the adult mammalian brain. This perspective
      examines the origins of this dogma, its perseverance in the face of contradictory
      evidence, and its final collapse. The acceptance of adult neurogenesis may be
      part of a contemporary paradigm shift in our view of the plasticity and stability
      of the adult brain.

PMID- 11252771
TI  - Transcranial magnetic stimulation and cognitive neuroscience.
AB  - Transcranial magnetic stimulation has been used to investigate almost all areas
      of cognitive neuroscience. This article discusses the most important (and least
      understood) considerations regarding the use of transcranial magnetic stimulation
      for cognitive neuroscience and outlines advances in the use of this technique for
      the replication and extension of findings from neuropsychology. We also take a
      more speculative look forward to the emerging development of strategies for
      combining transcranial magnetic stimulation with other brain imaging technologies
      and methods in the cognitive neurosciences.

PMID- 11252772
TI  - New perspectives on spinal motor systems.
AB  - The production and control of complex motor functions are usually attributed to
      central brain structures such as cortex, basal ganglia and cerebellum. In
      traditional schemes the spinal cord is assigned a subservient function during the
      production of movement, playing a predominantly passive role by relaying the
      commands dictated to it by supraspinal systems. This review challenges this idea
      by presenting evidence that the spinal motor system is an active participant in
      several aspects of the production of movement, contributing to functions normally
      ascribed to 'higher' brain regions.

PMID- 11252773
TI  - Molecular genetics: unmasking polyglutamine triggers in neurodegenerative
      disease.
AB  - Two decades ago, molecular genetic analysis provided a new approach for defining
      the roots of inherited disorders. This strategy has proved particularly powerful
      because, with only a description of the inheritance pattern, it can uncover
      previously unsuspected mechanisms of pathogenesis that are not implicated by
      known biological pathways or by the disease manifestations. Nowhere has the
      impact of molecular genetics been more evident than in the dominantly inherited
      neurodegenerative disorders, where eight unrelated diseases have been revealed to
      possess the same type of mutation--an expanded polyglutamine encoding sequence-
      affecting different genes.

PMID- 11252774
TI  - Patterning the cranial neural crest: hindbrain segmentation and Hox gene
      plasticity.
AB  - Understanding the patterning mechanisms that control head development-
      particularly the neural crest and its contribution to bones, nerves and
      connective tissue--is an important problem, as craniofacial anomalies account for
      one-third of all human congenital defects. Classical models for craniofacial
      patterning argue that the morphogenic program and Hox gene identity of the neural
      crest is pre-patterned, carrying positional information acquired in the hindbrain
      to the peripheral nervous system and the branchial arches. Recently, however,
      plasticity of Hox gene expression has been observed in the hindbrain and cranial
      neural crest of chick, mouse and zebrafish embryos. Hence, craniofacial
      development is not dependent on neural crest prepatterning, but is regulated by a
      more complex integration of cell and tissue interactions.

PMID- 11252775
TI  - Information processing with population codes.
AB  - Information is encoded in the brain by populations or clusters of cells, rather
      than by single cells. This encoding strategy is known as population coding. Here
      we review the standard use of population codes for encoding and decoding
      information, and consider how population codes can be used to support neural
      computations such as noise removal and nonlinear mapping. More radical ideas
      about how population codes may directly represent information about stimulus
      uncertainty are also discussed.

PMID- 11252776
TI  - Postsynaptic organization and regulation of excitatory synapses.
AB  - Dynamic regulation of synaptic efficacy is one of the mechanisms thought to
      underlie learning and memory. Many of the observed changes in efficacy, such as
      long-term potentiation and long-term depression, result from the functional
      alteration of excitatory neurotransmission mediated by postsynaptic glutamate
      receptors. These changes may result from the modulation of the receptors
      themselves and from regulation of protein networks associated with glutamate
      receptors. Understanding the interactions in this synaptic complex will yield
      invaluable insight into the molecular basis of synaptic function. This review
      focuses on the molecular organization of excitatory synapses and the processes
      involved in the dynamic regulation of glutamate receptors.

PMID- 11252777
TI  - Circadian clockwork: two loops are better than one.
AB  - The spectacularly successful race over the past three years to place our
      understanding of the circadian clockwork of mammals into a molecular framework is
      beginning to yield the cardinal example of the molecular-genetic control of
      behaviour. This perspective describes recent evidence for the conservation of a
      double-loop, autoregulatory feedback mechanism across the best understood
      eukaryotic circadian systems, and discusses how these findings may illuminate
      some long-standing puzzles concerning our subliminal sense of circadian time.

PMID- 11252778
TI  - Shifting baselines in attention research.
AB  - Psychophysical and physiological studies have shown that attending to a stimulus
      can enhance its sensory processing. Functional imaging studies now reveal that
      attention can also modulate activity in sensory brain areas before stimulus
      onset, when the observer prepares to attend to an anticipated stimulus. These
      preparatory 'baseline shifts' in brain activity pose many new questions, and
      potentially offer new insights into the neural basis of perceptual awareness.

PMID- 11252779
TI  - Visual attention: insights from brain imaging.
AB  - We are not passive recipients of the information that impinges on our retinae,
      but active participants in our own perceptual processes. Visual experience
      depends critically on attention. We select particular aspects of a visual scene
      for detailed analysis and control of subsequent behaviour, but ignore other
      aspects so completely that moments after they disappear from view we cannot
      report anything about them. Here we show that functional neuroimaging is
      revealing much more than where attention happens in the brain; it is beginning to
      answer some of the oldest and deepest questions about what visual attention is
      and how it works.

PMID- 11252780
TI  - Optimization of heterologous gene expression for in vitro evolution.

PMID- 11252781
TI  - Vectors for the generation of FLAG- or EGFP-tagged cDNA constructs and EGFP
      tagged antisense RNA constructs.

PMID- 11252783
TI  - General method for site-directed mutagenesis.

PMID- 11252782
TI  - Targeting random mutations to regions that are not flanked by existing
      restriction sites.

PMID- 11252784
TI  - Exon amplification restriction ligation (EARL): an efficient strategy for direct
      sequencing of exons.

PMID- 11252785
TI  - Improved PCR-walking for large-scale isolation of plant T-DNA borders.

PMID- 11252786
TI  - Use of fluorescently labeled DNA and a scanner for electrophoretic mobility shift
      assays.

PMID- 11252787
TI  - Generation of full-length cDNA libraries enriched for differentially expressed
      genes for functional genomics.
AB  - Here, we describe the application of a RecA-based cloning technology to generate
      full-length cDNA libraries enriched for genes that are differentially expressed
      between tumor and normal tissue samples. First, we show that the RecA-based
      method can be used to enrich cDNA libraries for several target genes in a single
      reaction. Then, we demonstrate that this method can be extended to enrich a cDNA
      library for many full-length cDNA clones using fragments derived from a
      subtracted cDNA population. The results of these studies show that this RecA
      mediated cloning technology can be used to convert subtracted cDNAs or a mixture
      of several cDNA fragments corresponding to differentially expressed genes into a
      full-length library in a single reaction. This procedure yields a population of
      expression-ready clones that can be used for further high-throughput functional
      screening.

PMID- 11252788
TI  - Oligonucleotide-mediated, PCR-independent cloning by homologous recombination.
AB  - We have developed an oligonucleotide-mediated cloning technique based on
      homologous recombination in Saccharomyces cerevisiae that allows precise DNA
      sequences to be transferred independent of restriction enzymes and PCR. In this
      procedure, linear DNA sequences are targeted to a chosen site in a yeast vector
      by DNA linkers, which consist of two partially overlapping oligonucleotides. The
      linkers contain relatively short regions of both yeast vector sequences and
      insert sequences, which stimulate homologous recombination between the vector and
      the insert. The linkers can also contain sequences not found in either the vector
      or the insert (e.g., sequences that encode ribosome binding sites, epitope tags,
      preferred codons, etc.), thus allowing modification of the transferred DNA.
      Linkers can be designed such that DNA sequences can be transferred with just two
      reusable universal oligonucleotides and two gene-specific oligonucleotides. This
      cloning method, which is performed by co-transforming yeast with linear vector,
      substrate DNA, and unannealed oligonucleotides, has been termed the yeast-based,
      oligonucleotide-mediated gap repair technique (YOGRT).

PMID- 11252789
TI  - Set of vectors for the expression of histidine-tagged proteins in vaccinia virus
      recombinants.
AB  - Vaccinia virus expression vectors are widely used to direct the expression of
      proteins in eukaryotic cells. Here, we describe a new set of plasmid vectors
      designed for the expression of histidine-tagged proteins in the vaccinia system.
      To facilitate the rapid isolation of virus recombinants, the plasmids contain a
      viral gene (F13L) that serves as an efficient selection marker based on virus
      plaque phenotype. Histidine codons and restriction sites derived from pET-16b
      bacterial expression plasmid were included, thus facilitating the transfer of
      genes between E. coli and vaccinia expression plasmids. Plasmids in which the
      gene is placed downstream of either a strong vaccinia virus or a T7 promoter were
      constructed, allowing for constitutive or conditional expression, respectively,
      of the foreign protein.

PMID- 11252790
TI  - High-fidelity in vitro recombination using a proofreading polymerase.
AB  - We describe a convenient PCR-based protocol for in vitro recombination of
      homologous genes, thereby minimizing the rate of associated point mutations. High
      fidelity recombination conditions were obtained using Vent DNA polymerase, which,
      in contrast to Taq DNA polymerase, shows significant proofreading activity and
      ranges among the slowest thermostable DNA polymerases, allowing tight control of
      the polymerase-catalyzed DNA extension. To determine the mutagenesis rate and to
      analyze the efficiency of recombination, 89 clones from a standard experiment
      were randomly selected for further analysis. Sequence comparison revealed that
      21% (19/89) of the clones result from different recombination events in the
      marker-containing region (260 bp). The overall mutation rate is only 0.02%, which
      is the lowest rate thus far reported for in vitro recombination experiments.

PMID- 11252791
TI  - Large-scale purification of a stable form of recombinant tobacco etch virus
      protease.
AB  - Tobacco etch virus NIa proteinase (NIa-Pro) has become the enzyme of choice for
      removing tags and fusion domains from recombinant proteins in vitro. We have
      designed a mutant NIa-Pro that resists autoproteolytic inactivation and present
      an efficient method for producing large amounts of this enzyme that is highly
      pure, active, and stable over time. Histidine-tagged forms of both wild-type and
      mutant NIa-Pro were overexpressed in E. coli under conditions in which greater
      than 95% of the protease was in the insoluble fraction after cell lysis. An
      inclusion body preparation followed by denaturing purification over a single
      affinity column and protein renaturation yields greater than 12.5 mg enzyme per
      liter of bacterial cell culture. NIa-Pro purified according to this protocol has
      been used for quantitative removal of fusion domains from a variety of proteins
      prepared for crystallization and biochemical analysis.

PMID- 11252792
TI  - Multicolor fluorescent differential display.
AB  - Differential display and DNA microarray have emerged as the two most popular
      methods for gene expression profiling. Here, we developed a multicolor
      fluorescent differential display (FDD) method that combines the virtues of both
      differential display in signal amplification and DNA microarray in signal
      analysis. As in DNA microarray, RNA samples being compared can be labeled with
      either a red or green fluorescent dye and displayed in a single lane, allowing
      convenient scoring and quantification of the differentially expressed messages.
      In addition, the multicolor FDD has a built-in signal proofreading capability
      that is achieved by labeling each RNA sample from a comparative study with both
      red and green fluorescent dyes followed by their reciprocal mixings in color.
      Thus, the multicolor FDD provides a platform upon which a sensitive and accurate
      gene expression profiling by differential display can be automated and digitally
      analyzed. It is envisioned that cDNAs generated by the multicolor FDD may also be
      used directly as probes for DNA microarray, allowing an integration of the two
      most widely used technologies for comprehensive analysis of gene expression.

PMID- 11252793
TI  - Reverse transcriptase adds nontemplated nucleotides to cDNAs during 5'-RACE and
      primer extension.
AB  - In determining the terminal sequences of the genomic dsRNAs of rotavirus by 5'
      rapid amplification of cDNA ends (5'-RACE), it was found that most of the viral
      cDNAs contained extra nucleotides at their 5' termini that had not been reported
      before on any rotavirus sequence. Although the extra nucleotides could be dA, dC,
      dG, or dT residues, the extra nucleotides on the cDNAs usually consisted of a
      single dT residue. Experiments performed with DNA/RNA duplexes indicated that
      reverse transcriptase has an associated terminal nucleotidyl transferase (TdT)
      like activity, which can add nontemplated nucleotides to the 3' ends of DNA, and
      that reverse transcriptase was responsible for the presence of the extra
      nucleotides detected on the 5'-RACE cDNAs. The TdT-like activity of reverse
      transcription was specific for double-stranded substrates (i.e., DNA/DNA or
      DNA/RNA duplexes) and was active over a wide range of temperatures and enzyme
      concentrations. Both commercially available Moloney murine leukemia virus and
      avian myeloblastosis virus reverse transcriptases contained the TdT-like
      activity. This work implies that 5'-RACE and primer extension assays must be used
      carefully in determining the terminal sequences of nucleic acids because, under
      standard reaction conditions, reverse transcriptase can add nontemplated
      nucleotides to the 3' ends of cDNAs following template-directed synthesis.

PMID- 11252794
TI  - Synthesis and application of circularizable ligation probes.
AB  - We describe a PCR-based approach for the synthesis of circularizable ligation
      probes (CLiPs). CLiPs are single-stranded probes that consist of target-specific
      ends separated by a noncomplementary "linker" sequence. When hybridized to a
      target, the CLiP forms a nicked circle that may be sealed by DNA ligase only if
      the 5' and 3' ends show perfect Watson-Crick base pairing, thus enabling the
      discrimination of single nucleotide polymorphisms. Primers incorporating target
      sequence at their 5' end and plasmid sequence at the 3' end were used in a PCR
      amplification. In addition, the antisense primer was 5' labeled with biotin, and
      the amplification was performed in the presence of fluorescently labeled dUTP.
      The resulting PCR product was captured with streptavidin-coated paramagnetic
      beads, and the top strand, which forms the CLiP, was alkali eluted. This PCR
      based method has allowed the synthesis of CLiPs that are larger and more highly
      labeled than has previously been possible, with ligation efficiencies similar to
      those of the purest chemically synthesized padlock probes. Ligations performed in
      the presence of cognate or mismatched sequence were analyzed by denaturing PAGE
      using a fluorescent DNA sequencer. Genotyping using target immobilized to nylon
      membranes was also performed. The CLiPs were readily able to distinguish between
      mutant and wild-type alleles for the common genetic disorder, 21-hydroxylase
      deficiency. Additionally, CLiPs of different lengths were synthesized and
      compared.

PMID- 11252795
TI  - Microfluorometer assay to measure the expression of beta-galactosidase and green
      fluorescent protein reporter genes in single Drosophila flies.
AB  - beta-galactosidase and green fluorescent protein (GFP) are among the most
      commonly used reporter genes to monitor gene expression in various organisms
      including Drosophila melanogaster. Their expression is usually detected in a
      qualitative way by direct microscopic observations of cells, tissues, or whole
      animals. To measure in vivo the inducibility of two antimicrobial peptide genes
      expressed during the Drosophila innate immune response, we have adapted two
      reporter gene systems based on the beta-galactosidase enzymatic activity and GFP.
      We have designed a 96-well microplate fluorometric assay sensitive enough to
      quantify the expression of both reporter genes in single flies. The assay has
      enabled us to process efficiently and rapidly a large number of individual mutant
      flies generated during an ethylmethane sulfonate saturation mutagenesis of the
      Drosophila genome. This method may be used in any screen that requires the
      quantification of reporter gene activity in individual insects.

PMID- 11252796
TI  - PCR-ELISAs for the detection of Campylobacter jejuni and Campylobacter coli in
      poultry samples.
AB  - Campylobacter species, primarily Campylobacter jejuni and Campylobacter coli, are
      regarded as a major cause of human gastrointestinal disease, commonly acquired by
      eating undercooked chicken. We describe a PCR-ELISA for the detection of
      Campylobacter species and the discrimination of C. jejuni and C. coli in poultry
      samples. The PCR assay targets the 16S/23S ribosomal RNA intergenic spacer region
      of Campylobacter species with DNA oligonucleotide probes designed for the
      specific detection of C. jejuni, C. coli, and Campylobacter species immobilized
      on Nucleo-Link wells and hybridized to PCR products modified with a 5' biotin
      moiety. The limit of detection of the PCR-ELISA was 100-300 fg (40-120 bacterial
      cells) for C. jejuni and C. coli with their respective species-specific
      oligonucleotide probes and 10 fg (4 bacterial cells) with the Campylobacter genus
      specific probe. Testing of poultry samples, which were presumptive positive for
      Campylobacter following culture on the Malthus V analyzer, with the PCR-ELISA
      determined Campylobacter to be present in 100% of samples (n = 40) with mixed
      cultures of C. jejuni/C. coli in 55%. The PCR-ELISA when combined with culture
      pre-enrichment is able to detect the presence of Campylobacter and definitively
      identify C. jejuni and C. coli in culture-enriched poultry meat samples.

PMID- 11252797
TI  - Simultaneous insertion of two expression cassettes into adenovirus vectors.
AB  - We have designed AdenoQuick, a fast and versatile method to construct first
      generation adenoviral vectors that contain one or two transgenes in the E1 and/or
      the E3 region. The method is based on the reconstitution of the entire genome of
      the desired recombinant virus in E. coli and the subsequent transfection of the
      DNA in a helper cell line. Since the construction of large adenoviral plasmids is
      generally difficult and therefore rebuffing for inexperienced researchers, we
      have optimized the cloning strategy by using bacterial positive-selection markers
      and a set of specific restriction enzymes that allow for directional cloning. The
      system is 99% efficient and allows one to insert simultaneously two expression
      cassettes into the E1 and E3 regions of the adenovirus genome.

PMID- 11252798
TI  - Cancer--emerging breakthrough drugs.

PMID- 11252799
TI  - Redefinition of the yeast two-hybrid system in dialogue with changing priorities
      in biological research.
AB  - Examination of the pattern of reagent creation and application in the two-hybrid
      system since 1989 reveals the expansion of a simple core technology to address
      increasingly sophisticated problems in protein interaction. As the technology has
      matured, its clear suitability for large-scale proteomic projects has made a
      major focus of its application the generation of global organismal protein
      interaction networks. In an inversion of emphasis, the increasing availability of
      such information now provides a master plan with the potential to specify the
      most promising directions for biological investigations (i.e., by directing the
      physiological validation of predicted critical protein-protein interactions).
      Recent derivatives of the two-hybrid system enable the targeting of such key
      interactions by facilitating the identification of essential amino acids
      conferring protein interaction specificity and of small molecules that
      selectively disrupt defined interaction pairs. Finally, the creation of mammalian
      expression systems based on two-hybrid principles became a new tool to create and
      probe novel biological systems. Taken in sum, this trajectory emphasizes the
      point that the creation of tools and the evolution of the idea of what is an
      interesting biological problem are in intimate dialogue.

PMID- 11252800
TI  - Use of short-lived green fluorescent protein for the detection of proteasome
      inhibition.
AB  - Human embryonic kidney (HEK293) cells were stably transduced with a retroviral
      vector containing an expression cassette for a short-lived green fluorescent
      protein (d2EGFP) and the neomycin resistance gene (Neor). When Neor HEK293 clones
      were treated with proteasome inhibitors, lactacystin or MG132, an increase in the
      constitutive levels of d2EGFP expression was observed. Based on flow cytometry,
      proteasome inhibitors induced a 5- to 10-fold increase in the fluorescent
      intensity of d2EGFP in HEK293 cell clones. However, in the presence of proteasome
      inhibitors, HEK293 clones showed a 4- to 6.5-fold increase in d2EGFP
      concentration as determined by western blot analysis. Our data suggest that
      d2EGFP is a useful indicator of proteasome inhibition. Therefore, stable
      expression of d2EGFP in mammalian cells is potentially useful for high-throughput
      screening of cDNAs or pharmaceutical drugs that repress proteasome functions in
      vivo.

PMID- 11252801
TI  - Flow cytometric platform for high-throughput single nucleotide polymorphism
      analysis.
AB  - We have developed a rapid, cost-effective, high-throughput readout for single
      nucleotide polymorphism (SNP) genotyping using flow cytometric analysis performed
      on a Luminex 100 flow cytometer. This robust technique employs a PCR-derived
      target DNA containing the SNP, a synthetic SNP-complementary ZipCode-bearing
      capture probe, a fluorescent reporter molecule, and a thermophilic DNA
      polymerase. An array of fluorescent microspheres, covalently coupled with
      complementary ZipCode sequences (cZipCodes), was hybridized to the reaction
      products and sequestered them for flow cytometric analysis. The single base chain
      extension (SBCE) reaction was used to assay 20 multiplexed SNPs for 633 patients
      in 96-well format. Comparison of the microsphere-based SBCE assay results to gel
      based oligonucleotide ligation assay (OLA) results showed 99.3% agreement in
      genotype assignments. Substitution of direct-labeled R6G dideoxynucleotide with
      indirect-labeled phycoerythrin dideoxynucleotide enhanced signal five- to tenfold
      while maintaining low noise levels. A new assay based on allele-specific primer
      extension (ASPE) was validated on a set of 15 multiplexed SNPs for 96 patients.
      ASPE offers both the advantage of streamlining the SNP analysis protocol and the
      ability to perform multiplex SNP analysis on any mixture of allelic variants.

PMID- 11252802
TI  - Identification of differentially expressed genes from ovarian cancer cells by
      MICROMAX cDNA microarray system.
AB  - Using the MICROMAX cDNA microarray system, we were able to identify genes that
      are differentially overexpressed in ovarian cancer. A total of 30 putative genes,
      which are differentially overexpressed in ovarian cancer cell lines, were
      identified. The differential expression of some of these genes was further
      confirmed by real-time RT-PCR. Using this strategy, we have identified genes that
      either overexpress in all cancer cell lines or in only some cancer cell lines.
      Further characterization of these genes will allow them to be exploited in
      diagnosis, prognosis, anticancer therapy, and molecular classification of ovarian
      cancer.

PMID- 11252803
TI  - Using a CCD camera imaging system as a recording device to quantify human DNA by
      slot blot hybridization.
AB  - Slot blot hybridization of membrane-immobilized, single-stranded human DNA with
      the higher primate-specific alphoid probe D17Z1 is routinely used in forensic
      science to estimate the amount of DNA in biological samples. Typically, a
      chemiluminescent signal captured on film records the hybridization, and the
      quantity of the signal is related to the amount of immobilized DNA. Digital
      imaging using a cooled CCD camera offers an alternate non-film-based method for
      image acquisition with comparable sensitivity of detection, a greater dynamic
      range, enhanced capability of data interpretation, and often faster results than
      film. In addition, the data support the premise that more accurate and precise
      human DNA quantification should be obtained by not assuming a linear response of
      signal to known standards. Instead, quantity should be estimated using a second
      order standard curve (R2 = 0.999). Finally, a CCD camera imaging system offers
      versatility for image capture of different signal sources and analysis of samples
      on a variety of support media.

PMID- 11252804
TI  - Comparison of Escherichia coli, Saccharomyces cerevisiae, Pichia pastoris,
      Spodoptera frugiperda, and COS7 cells for recombinant gene expression.
      Application to a rabbit liver carboxylesterase.
AB  - Expression of a rabbit liver carboxylesterase has been achieved in several
      different model systems including Escherichia coli, Pichia pastoris,
      Saccharomyces cerevisiae, Spodoptera frugiperda, and COS7 cells. Although,
      recombinant protein was observed in E. coli sonicates, little or no enzymatic
      activity was detected. Similarly, no activity was observed following expression
      in S. cerevisiae. In contrast, active protein was produced in P. pastoris, from
      S. frugiperda following baculoviral infection and in COS7 cells following
      transient transfection of plasmid DNA. For the preparation of small amounts of
      protein for kinetic and biochemical studies, enzyme expressed in P. pastoris has
      proved sufficient. However, to produce large amounts of carboxylesterase for
      structural studies, baculoviral-mediated expression of a secreted form of the
      protein in S. frugiperda was the most efficient. Using this system, we have
      generated and purified milligram quantities of essentially pure protein. These
      results demonstrate that the choice of in vitro system for the generation of
      large amounts of active carboxylesterase, and probably most endoplasmic reticulum
      processed proteins, is crucial for high level expression and subsequent
      purification.

PMID- 11252805
TI  - Isolation of a cDNA sequence of rabbit GDF5 (mature form) and pattern of its mRNA
      expression during periosteal chondrogenesis.
AB  - Articular cartilage has a limited ability for repair and/or regeneration.
      Periosteal grafts, having chondrogenic potential, are used clinically and in
      experimental models to study the repair and regeneration of cartilage.
      Growth/differentiation factor 5 (GDF5), recently shown to be involved in
      chondrogenesis and normal skeletal development, is a bioactive candidate for
      augmenting the repair of damaged cartilage. In order to investigate the role of
      GDF5 during periosteal chondrogenesis, the rabbit sequence must be known, as most
      experimental models involve rabbit tissues. For this purpose, the complete rabbit
      specific cDNA sequence of the mature form of GDF5 was determined. Mature rabbit
      GDF5 was found to be 100% identical to that of human GDF5 at the amino acid
      level. Using the cDNA sequence, specific primers for PCR were designed.
      Quantitative RT-PCR, using rabbit-specific primers, showed up-regulation of GDF5
      mRNAs early during periosteal chondrogenesis suggesting its potential involvement
      in this process. The timing and magnitude of this expression was markedly
      stimulated by TGF-beta 1, which has already been shown to be a potent inducer of
      periosteal chondrogenesis.

PMID- 11252807
TI  - Annotating sequence data using Genotator.
AB  - In this postgenomic era, it is no longer necessary to argue the need for
      automated methods for sequence annotation. Many researchers have designed tools
      for analyzing DNA sequences, but running multiple tools and interpreting the
      results can be tedious and confusing. In the last few years, many analysis
      workbenches have been developed to help streamline the process of sequence
      annotation. Genotator, developed in 1996, is still a popular choice owing to its
      ease of use and its configurability. This article will review annotating sequence
      data using the Genotator.

PMID- 11252806
TI  - Cytoplasmic expression of a soluble synthetic mammalian metallothionein-alpha
      domain in Escherichia coli. Enhanced tolerance and accumulation of cadmium.
AB  - Bacteria are commonly used for bioremediation of heavy metal pollution and
      strategies to improve their performance in this respect are desirable. In this
      study, an Escherichia coli strain was engineered to express a common
      metallothionein-alpha domain. The metallothionein-alpha domain was over-expressed
      in the cytoplasm of E. coli as a fusion to the carboxyl terminal of maltose
      binding protein. The fusion protein was highly soluble in the cytoplasm of E.
      coli. When grown in the presence of cadmium, cells expressing the metallothionein
      alpha fusion protein showed increased viability compared with control cells.
      Cells expressing the metallothionein-alpha also demonstrated increased
      accumulation of cadmium.

PMID- 11252809
TI  - Application of the E. coli trp promoter.
AB  - The Escherichia coli tryptophan (trp) promoter has been used extensively for the
      high level production of proteins on a small and large scale. This regulated
      promoter is readily available, relatively easy to turn on, and can be used in
      essentially any E. coli host background. This article gives a detailed use of the
      trp promoter including the design of expression vectors, subsequent culture
      conditions for promoter induction, and, finally, a protocol for the most common
      way of detecting the newly synthesized protein of interest. Its successful use
      for heterologous protein expression, however, sometimes requires consideration of
      parameters other than transcription such as translation initiation, translation
      elongation, and proteolysis. In this respect we offer guidance in getting through
      these post-transcriptional problems, which can occur with the use of any
      promoter.

PMID- 11252810
TI  - Terminal restriction fragment length polymorphism monitoring of genes amplified
      directly from bacterial communities in soils and sediments.
AB  - Terminal Restriction Fragment Length Polymorphism (T-RFLP) or Fluorescent
      Polymerase Chain Reaction/Restriction Fragment Length Polymorphism (FluRFLP) have
      made a significant impact on the way in which PCR products amplified from mixed
      community DNA extracts have been assessed. Technically, these approaches are
      essentially the same. PCR products are generated that contain at one 5' end
      label, typically a fluorescent moiety, that will be detected by a DNA sequencing
      machine. Upon digestion using a specific restriction endonuclease, labeled and
      unlabeled fragments are generated. This restriction endonuclease is chosen such
      that following this digestion, each labeled fragment corresponds to a different
      sequence variant. During electrophoretic separation, the DNA sequencing machine
      detects only these labeled fragments and therefore detects only the sequence
      variants. The aim of this article is to describe the protocols and demonstrate
      that this profiling can be performed using different DNA sequencing machines. The
      analysis and applications of this approach are also discussed.

PMID- 11252811
TI  - Approaches of the diagnosis of hepatitis viruses.
AB  - Hepatitis virus infection occurs in close to a billion people worldwide at some
      point in their lifetimes. Hepatitis B and C viruses together account for
      infections in half a billion people and are considered the most carcinogenic of
      any known biological agent. The diagnostic approaches to detect hepatitis viruses
      are discussed.

PMID- 11252808
TI  - Epoxygenase metabolites. Epithelial and vascular actions.
AB  - Cytochrome P450 (CYP450) epoxygenase enzymes demonstrate organ and cell specific
      expression and each CYP450 enzyme isoform produces a distinct pattern of
      epoxyeicosatrienoic acids (EETs). Investigations are beginning to describe the
      regulation of specific tissue CYP450 epoxygenase isoforms that may be associated
      with alterations in organ function that occur during various physiological and
      pathophysiological states. The main biological actions of EETs are their ability
      to affect epithelial ion transport and vascular smooth muscle cell function. This
      chapter focuses on the organ localization and production of EETs and the action
      of EETs on epithelial and vascular smooth muscle cells.

PMID- 11252812
TI  - Intrauterine exposure to diethylstilbestrol: long-term effects in humans.
AB  - DES is the most carefully scrutinized EDC and its history provides valuable
      insights into the current evaluation of less well-studied EDCs. This review
      summarizes the health effects of prenatal exposure to diethylstilbestrol (DES)
      and emphasizes the role of DES as the first endocrine disrupting chemical (EDC).
      Vaginal clear cell adenocarcinoma (CCAC), the most severe consequence of prenatal
      exposure to DES, affected only 0.1% of exposed females, while the far more
      prevalent teratogenic and reproductive effects of DES were only discovered when
      DES daughter were screened for CCAC. Initial studies, conducted before most DES
      daughters had tried to conceive, examined vaginal cancer and vaginal, cervical
      and uterine abnormalities. Subsequently, several controlled studies demonstrated
      the increased risk of adverse reproductive outcomes in DES daughters. While most
      DES daughters can eventually experience a live birth, this is less likely in
      women with genital tract abnormalities, in whom there is a two-thirds chance that
      each pregnancy will be unsuccessful. In DES sons, who have been far less studied,
      results suggest male reproductive toxicity, but are less consistent. The
      importance of dose and gestational age at initial exposure are discussed, and the
      implications of DES findings for the evaluation of risks from current EDCs
      emphasized.

PMID- 11252813
TI  - Getting the problem of endocrine disruption into focus: the need for a pause for
      thought.
AB  - The study of chemically-induced endocrine disruption in mammals is a relatively
      new field of endeavour, and it has been assailed by an unusual level of
      disagreement among investigators regarding the developmental effects produced by
      chemicals in animals. This article discusses the several sources of uncertainty
      in endocrine toxicity studies, and the intrinsic variability of many of the key
      experimental parameters. It is concluded that current uncertainties are due to
      the absence of an extensive agreed control database for the developmental
      parameters under study, coupled to the established intrinsic variability of these
      parameters between strains/species of test animals and test protocols. Only when
      these factors are generally accepted and well studied will it be possible to
      design studies capable of distinguishing the possible subtle endocrine toxicity
      of chemicals and chance observations that cannot be independently reproduced.

PMID- 11252814
TI  - An outbreak of trichinellosis in farmed wild boar in Finland.
AB  - Nine farmed wild boar out of 25 slaughtered from a single farm were condemned at
      meat inspection because of trichinellosis. With RAPD-PCR, Trichinella spiralis
      was identified in all positive wild boar. Out of the available serum samples
      (n=7), all wild boar which had failed the meat inspection showed seroconversion
      in ELISA and Western blotting, as did one additional animal which had passed the
      inspection. The animals became infected during an invasion of rats from an
      improperly closed dump near the farm. Unfortunately, by the time trichinellosis
      was discovered in the wild boar, the invasion had already been brought under
      control; thus, no samples from rats were available. However, having lived through
      the rat invasion was shown to be a risk factor for trichinellosis in wild boar
      (relative risk, RR=6.3). In wildlife samples from surrounding areas, sylvatic
      trichinellosis was found to be very common (74%; n= 19 red foxes). Intriguingly,
      the prevalent species in trichinella-positive foxes differed from that in wild
      boar, Trichinella nativa and T. spiralis being found in 12 foxes and in one fox,
      respectively.

PMID- 11252815
TI  - Comparison of a new commercial EIA kit and the microimmunofluorescence technique
      for the determination of IgG and IgA antibodies to Chlamydia pneumoniae.
AB  - Chlamydia pneumoniae infection is often diagnosed by analyzing specific
      antibodies to C. pneumoniae in sera. The method which has been used as the
      reference method, or "gold standard", the microimmunofluorescence test (MIF),
      demands a high level of experience for proper interpretation. A number of
      commercial enzyme immunoassay (EIA) tests have been introduced to the market in
      the past few years. These provide objective reading of titers, but are genus
      specific and not species specific. The latest EIA introduced, LabSystems EIA for
      C. pneumoniae, was investigated using several groups of clinically relevant
      patient sera in a comparison with MIF. It was found that the LabSystems EIA did
      not discriminate between antibodies to C. trachomatis and C. pneumoniae when
      tested with sera containing high titers of C. trachomatis antibodies. The
      correlation between C. pneumoniae EIA and MIF IgG and IgA titers was, however,
      good in the patient groups not having a high background of C. trachomatis
      antibodies: hypertensives, n= 199 and patients with chronic C. pneumoniae
      infections and ischaemic heart disease, n=33. In conclusion, the LabSystems EIA
      is a method which can be useful for screening populations with low prevalences of
      C. trachomatis/C. psittaci infection for antibodies to C. pneumoniae. It cannot
      replace the MIF test due to the lack of discrimination between different
      chlamydial antibody types.

PMID- 11252816
TI  - Long-wave UVA offers partial protection against UVB-induced immune suppression in
      human skin.
AB  - Ultraviolet-B (UVB, 280-320 nm) interferes with the generation of cell-mediated
      immunity to contact allergens applied epicutaneously on the irradiated site. To
      investigate whether pretreatment with UVA-1 (340-400 nm) protects against the UVB
      induced immune suppression we sensitized human volunteers with
      diphenylcyclopropenone (DPCP) on normal buttock skin (n= 12), on UVB-irradiated
      buttock skin (n=21), on buttock skin pretreated with UVA-1 (n= 12), and on
      buttock skin pretreated with UVA-1 and thereafter irradiated with UVB (n=22).
      Sensitization on UVB-irradiated skin reduced the immunization rate to DPCP
      compared with sensitization on non-irradiated skin (p<0.01) and skin pretreated
      with UVA-1 (p<0.01). In contrast, the immunization rate in the group of
      volunteers sensitized on skin pretreated with UVA-1 before UVB irradiation was
      significantly higher than the immunization rate in the group of volunteers
      sensitized on UVB-irradiated skin alone (p<0.05). These results indicate that
      pretreatment with UVA-1 under certain conditions offers partial protection
      against the UVB-induced reduction in the immunization rates to epicutaneous
      allergens.

PMID- 11252817
TI  - Proliferative and cytotoxic capabilities of CD16+CD56- and CD16+/-CD56+ natural
      killer cells.
AB  - Natural killer (NK) cells can be divided into several subpopulations according to
      their expression of the surface antigens CD16 and CD56. The modest quantity of NK
      cells in the blood available for functional analysis has been a limitation in
      studies of NK cell subpopulations. In the present study, epinephrine infusion was
      used to induce lymphocytosis before immunomagnetic methods were applied to
      isolate CD16+/-CD56+ and CD16+CD56- CD3- NK cells. These subpopulations were
      compared according to their proliferative and cytotoxic capabilities in 10 human
      immunodeficiency virus (HIV)-infected individuals and 5 healthy controls. The
      CD16+CD56- NK cell subgroup had a higher proliferative capacity, whereas the
      CD16+/-CD56+ NK cell subgroup was mainly cytotoxic, and unaffected by HIV
      serostatus. This study thus suggests that NK cell phenotypes more strongly
      predict NK cell function than HIV serostatus. This assertion should be considered
      when studying NK cell function in subjects with a deviating composition of NK
      cells.

PMID- 11252819
TI  - Dose-dependent effects of melengestrol acetate (MGA) on plasma levels of
      estradiol, progesterone and luteinizing hormone in cycling heifers and influences
      on oestrogen residues in edible tissues.
AB  - Melengestrol acetat (MGA) is widely used as a growth promoting feed additive in
      cattle breeding in the USA and several other non-European countries. To explore
      the physiological effects of MGA four heifers were fed during 8 weeks with 0.5 mg
      MGA daily as registered in the USA and two heifers each received 0, 1.5 or 5
      mg/day, respectively. Plasma samples were collected twice a week and
      concentrations of MGA, progesterone (P4) and estradiol-17beta (E2-17beta) were
      quantified. The pulsatile secretion of luteinizing hormone (LH) was investigated
      in 6-hour profiles before and during treatment. After slaughter the reproductive
      organs were examined and oestrogen residues in edible tissues were measured. Four
      days after the beginning of MGA feeding MGA concentrations in plasma reached
      levels of 30 and 100-400 pg/mL depending on the dose received. Three weeks after
      the beginning of MGA feeding P4 plasma concentrations had dropped to base levels
      below 0.3 ng/mL in all three treatment groups. Mean plasma E2-17beta levels
      increased in physiological range from 1 to 5 pg/mL during 0.5 mg MGA/day feeding
      with many acyclic peaks. Overdosed MGA decreased E2 levels and suppressed cyclic
      peaks. Number and size of ovarian follicles were not altered by any treatment.
      Mean LH levels and pulse frequencies increased significantly during labelled
      treatment (0.5 mg/day), while higher doses had reducing effects. The development
      of corpus luteum was suppressed. E2-17beta residues in fat increased about 300%
      following labelled MGA treatment.

PMID- 11252818
TI  - Characterisation of the affinity of different anabolics and synthetic hormones to
      the human androgen receptor, human sex hormone binding globulin and to the bovine
      progestin receptor.
AB  - For the steroidal growth promoters trenbolone acetate (TBA) and melengestrol
      acetate (MGA) neither the complete spectrum of biological activities nor the
      potential endocrine disrupting activity of their excreted metabolites in the
      environment is fully understood. The potency of these substances in
      [3H]dihydrotestosterone ([3H]-DHT) displacement from the recombinant human
      androgen receptor (rhAR) and from human sex-hormone binding globulin (hSHBG) was
      evaluated. In addition, the potency for [3H]-ORG2058 displacement from the bovine
      uterine progestin receptor (bPR) was tested. For comparison, different anabolics
      and synthetic hormones were also tested for their binding affinities. For 17beta
      trenbolone (17beta-TbOH), the active compound after TBA administration, an
      affinity the rhAR similar to dihydrotestosterone (DHT) and a slightly higher
      affinity to the bPR than progesterone were demonstrated. The affinity of the two
      major metabolites, 17alpha-trenbolone and trendione, was reduced to less than 5%
      of the 17beta-TbOH-value. The affinity of these three compounds and of MGA to the
      hSHBG was much lower compared with DHT. MGA showed a 5.3-fold higher affinity
      than progesterone to the bPR but only a weak affinity to the rhAR. The major MGA
      metabolites have an affinity to the bPR between 85% and 28% of the affinity of
      progesterone. In consequence, MGA and TBA metabolites may be hormonally active
      substances, which will be present in edible tissues and in manure. We conclude
      that detailed investigations on biodegradation, distribution and bio-efficacy of
      these substances are necessary.

PMID- 11252820
TI  - Massive parallel gene expression profiling of RINm5F pancreatic islet beta-cells
      stimulated with interleukin-1beta.
AB  - Interleukin 1 (IL-1) is a pleiotropic cytokine with the potential to kill
      pancreatic beta-cells, and this unique property is thought to be involved in the
      pathogenesis of type I diabetes mellitus. We therefore determined the
      quantitative expression of 24,000 mRNAs of RINm5F, an insulinoma cell line
      derived from rat pancreatic beta-cells, before and after challenge with 30 and
      1,000 pg/ml of recombinant human IL-1beta. The highest concentration resulted in
      decreased insulin production and cell death over a period of 4 days. Using three
      different time points, 2, 4 and 24 hours after challenge, we found that 146 full
      length genes and a large number of expressed sequence tags were differentially
      regulated 3-fold or more. Most of the differentially regulated transcripts have
      not previously been described to be regulated by IL-1beta in beta-cells. We have
      analysed the expression data and sorted the genes into groups according to
      functional relations on the basis of knowledge of the structure or function
      ascribed to the individual genes. Many of the differentially regulated genes are
      known to play a role in immune- and stress-related pathways as well as in insulin
      secretion and vesicle trafficking, e.g. alpha-endosulfine and K+ channel Kir6.2
      are differentially regulated. A number of transcripts in the biosynthesis pathway
      for cholesterol are also differentially regulated.

PMID- 11252821
TI  - Is there a role for gender-specific medicine in today's health care system?

PMID- 11252822
TI  - Advocating for gender-specific health care: a historical perspective.

PMID- 11252823
TI  - Women's health research at the NIH.

PMID- 11252824
TI  - Preventive gerontology: optimizing health and longevity for men and women across
      the lifespan.

PMID- 11252825
TI  - Health information on the Internet: how will it affect patient care?

PMID- 11252826
TI  - Healthy by law? The influence of labor and employment law on workers' health.

PMID- 11252827
TI  - The state of public policy on gender-based health care.

PMID- 11252828
TI  - Women's health as a model for change in academic medical centers: lessons from
      the National Centers of Excellence in Women's Health.

PMID- 11252829
TI  - Drug trials, gender, and Dr. Spilker: what is fad and what is science?

PMID- 11252830
TI  - Genetic discrimination.

PMID- 11252831
TI  - Funds for research on conditions primarily affecting women: what is a "fair
      share"?

PMID- 11252832
TI  - Gender differences in response to drugs: pain medications.
AB  - Differences exist between men and women in both perception of and response to
      pain. Whereas gender-related differences in pharmacokinetics may have confounded
      earlier studies of pain responses, emerging scientific evidence suggests gender
      related pharmacologic differences in central nervous system opioid mu-receptor
      binding and in responses to kappa-opioid pain medications. These differences
      suggest the importance of developing gender-specific strategies for pain relief
      and highlight the need for further investigation of gender-related pain treatment
      strategies.

PMID- 11252834
TI  - Sexual problems and dysfunction: epidemiology, classification, and risk factors.
AB  - Sexual difficulties are extremely prevalent among both men and women, occurring
      in about 43% of women and 31% of men. They are associated with a number of
      biological, medical, and psychological risk factors and increase markedly with
      aging. Sexual difficulties are also a significant source of emotional and
      relationship dissatisfaction. This article reviews and critiques the current
      classification system of sexual disorders and highlights the most common risk
      factors for sexual problems.

PMID- 11252833
TI  - Estrogen in autoimmunity: expression of estrogen receptors in thymic and
      autoimmune T cells.
AB  - OBJECTIVE: To identify the targets of estrogen in immune system lymphocytes and
      to examine gender differences in autoimmunity. DESIGN: RNA samples from purified
      lymphocyte subsets were analyzed for the presence of mRNA for estrogen receptor
      alpha and beta (ER alpha and ER beta). Groups of male, female, and testicular
      feminized mice were compared for autoantibody production. SUBJECTS: Autoimmune
      prone lpr (Fas-deficient), testicular-feminized (Tfm, androgen receptor
      deficient) and wild-type mice were studied. METHOD: Lymphocyte subsets were
      purified by fluorescence-activated cell sorting (FACS) and RNA was assessed for
      the presence of estrogen receptor sequences using specific oligonucleotide
      primers and the reverse transcription-polymerase chain reaction (RT-PCR).
      Spontaneous and induced antibody production in mice was determined by enzyme
      linked immunosorbent assay (ELISA). RESULTS: ER alpha was expressed in all
      lymphocyte subsets examined. ER beta was expressed at low levels in thymic
      CD4/CD8- T cells in wild-type mice and at high levels in the peripheral CD4-/CD8-
      T cells in lpr mice. Both spontaneous and induced autoantibody production was
      higher in female lpr mice than in male lpr mice. CONCLUSIONS: The presence of ERs
      in lymphocytes indicates that estrogen may affect immune cells during their
      development and mature function. The selective expression of ER beta may help
      explain some of the physiological effects of estrogen and its pharmacologic
      analogues and may lead to means to direct estrogen analogues to such cells. Such
      effects may be explored in lpr mice, given the enhanced capacity of female lpr
      mice for autoantibody production.

PMID- 11252835
TI  - Gender differences in leptin levels and physiology: a role for leptin in human
      reproduction.
AB  - Leptin, an adipocyte-derived hormone known to play an important role in body
      weight regulation, has been shown to be expressed differentially in men and
      women. These observations are potentially important for the understanding of
      differences between men and women in regulation of food intake, weight gain, and
      body fat distribution. Leptin is also involved in female fertility, especially in
      pubertal development. It may well be the triggering signal for the onset of
      puberty in girls. Although the exact mechanisms and interactions with sex
      steroids are not yet fully established, it is clear that leptin plays a role as
      an endocrine mediator in sexual development and reproduction.

PMID- 11252836
TI  - The impact of emotions on cardiovascular health.
AB  - Recent research suggests that the maintenance of emotional well-being is critical
      to cardiovascular health. People who feel lonely, depressed, and isolated have
      been found to be significantly more likely to suffer illnesses and to die
      prematurely of cardiovascular diseases than those who have adequate social
      support. Consequently, the development of appropriate interventions to improve
      the emotional health of people with certain psychosocial risk factors has become
      an important research goal. It is anticipated that such interventions will
      increase the life expectancy of people at risk and that it may also save millions
      of dollars in medical care costs. First, however, researchers in this field must
      identify specific emotional risk factors and must agree upon a working definition
      of "good emotional health." Such explicit definitions, as well as additional
      data, are essential to educating physicians and insurers so that consideration of
      emotional health can be integrated into basic medical care.

PMID- 11252837
TI  - The doctor's dilemma: what should we expect in the consulting room?

PMID- 11252838
TI  - Including women in clinical trials: the need for insurance coverage.

PMID- 11252839
TI  - Pharmacokinetics and pharmacodynamics of cardiovascular agents.

PMID- 11252840
TI  - Gender and race bias in medical treatment.

PMID- 11252841
TI  - Gender specificity of resting anterior electroencephalographic asymmetry and
      defensiveness in the elderly.
AB  - OBJECTIVE: It has been reported that defensiveness in women is associated with
      relative left-frontal electroencephalogram (EEG) activation, while defensiveness
      in men is associated with relative right-frontal EEG activation. The present
      study examined whether this result generalized to men and women between the ages
      of 58 and 70. DESIGN: The Marlowe-Crowne Social Desirability Scale (MCSD) and EEG
      testing were used to examine relationships between gender, defensiveness, and
      anterior asymmetry. PARTICIPANTS: Men (n = 18) and women (n = 54) between the
      ages of 58 and 70 (mean age = 64.22, standard deviation = 3.003) were recruited
      from Tucson and surrounding areas of Pima County, Arizona. They were selected
      from among participants in an integrative health sciences study of aging that
      took place between 1991 and 1993. METHOD: Subjects were divided into high
      defensive and low-defensive groups based on a median split on the MCSD. EEGs were
      recorded from 19 channels (standard 10-20 montage), referenced to linked ears,
      and digitalized on-line at 128 Hz (band pass 2-32 Hz) during consecutive 60
      second eyes-open and eyes-closed baselines. Two-second epochs containing
      bioelectric artifacts > 50 microvolts were eliminated from analyses. Average
      alpha (8-13 Hz) power (microV2)) was computed by Fast Fourier Transform and
      natural log (ln) transformed for normalization. Asymmetry scores were computed
      (log[right]-log[left]) for F4-F3, Fp2-Fp1, F8-F7, C4-C3, T4-T3, T6-T5, P4-P3, and
      O2-O1 for aggregated eyes-open and eyes-closed baselines. R-L asymmetry scores
      were analyzed for the aggregate frontal lead pairs, as well as for each pair
      separately. RESULTS: Findings were similar to those previously reported in that
      the direction of the relationship in men and women was the same. The results
      differed in that we found left-frontal activation in low-defensive men, whereas
      the previous study found right-frontal activation in high-defensive men.
      Furthermore, although in the same direction, the relationship for women was
      nonsignificant. CONCLUSION: These differences may have been due to the age of the
      participants, a lax impedence criterion, or the use of the MCSD rather than the L
      scale of the Eysenck Personality Questionnaire, as in the earlier study.
      Nevertheless, the findings suggest that gender differences in the relationship
      between resting anterior EEG asymmetry and defensiveness may persist throughout
      the life span.

PMID- 11252843
TI  - Management of headache in women.
AB  - Chronic headache is more prevalent in women than in men. In addition, women often
      experience increases in headache activity in relation to different life stages.
      Changes in headache pattern coincide with changes in estradiol levels, with
      elevated levels of estradiol (e.g., during pregnancy) associated with reduced
      headache, and cycling of estradiol (e.g., during menses) associated with worsened
      headache. Headache treatment for women must be modified to address the changes in
      headache that accompany menses, pregnancy, and menopause.

PMID- 11252842
TI  - Gender-specific response to depression treatment.
AB  - Gender-specific responses to pharmacotherapy or psychotherapy for depression are
      virtually unknown. Early studies rarely examined treatment response by gender,
      and the small number of males studied has led to inaccurate comparisons between
      male and female response. This article addresses conceptual issues and reviews
      what little can be ascertained from earlier studies of the relationship between
      gender and treatment outcome. It also presents data from a series of studies
      conducted over the last 15 years at the University of Pittsburgh School of
      Medicine.

PMID- 11252845
TI  - No boys allowed?

PMID- 11252844
TI  - Melanoma and pregnancy: eight questions with discussion.
AB  - In a question-and-discussion format, the authors summarize the major studies on
      melanoma and pregnancy. The laboratory studies reviewed give conflicting results;
      however, excellent epidemiologic studies suggest that pregnancy and melanoma are
      not closely linked. Specifically, the prognosis of pregnant women with melanoma
      is similar to the prognosis of nonpregnant women with melanoma of equal tumor
      thickness, and melanoma is neither more nor less likely to occur in previously
      pregnant women. Some studies have shown that pregnant women have melanomas that
      are thicker than nonpregnant women's melanomas. The reason is unclear, but it may
      be because malignant changes in pigmented lesions during pregnancy have been
      ignored. Treatment options for pregnant women with melanoma are limited, but
      early detection and surgical excision of thin melanomas is the goal. Changes in
      mole size or color during pregnancy can be normal, but all changing moles warrant
      careful examination, and irregular or asymmetric change is suspicious for
      melanoma.

PMID- 11252846
TI  - Gender, emotions, and cardiovascular disease.

PMID- 11252847
TI  - Women's health: where are all the men?

PMID- 11252848
TI  - The slow evolution of microbicides for STD/HIV prevention.

PMID- 11252849
TI  - The importance of folic acid.
AB  - Folic acid is necessary for cell development; for the metabolism of specific
      biochemical reactions in the body, such as the conversion of homocysteine to
      methionine; and for the metabolism of specific anticonvulsant drugs. Folic acid
      has an interrelationship with vitamin B12. A deficiency of folate increases the
      risk of NTDs, as well as contributing to hyperhomocystinemia, a condition
      associated with increased cardiovascular disease and NTDs. For the prevention of
      NTDs, it is recommended that a woman of childbearing age consume a daily folate
      intake of 400 micrograms; however, the average dietary folate intake is half that
      amount, and the FDA folate fortification of cereal grains adds only 100
      micrograms daily. The woman in her childbearing years does not meet the
      recommendation with dietary and food fortification. Periconceptional folic acid
      supplementation is essential, because the neural tube closes 23 to 27 days after
      conception. Therefore, a multiple vitamin containing folic acid is the practical
      solution at present if the food fortification is not increased. The
      bioavailability of folate in the vitamin preparation is approximately double that
      of dietary folate. Most preparations contain 400 micrograms of folic acid, and if
      the woman took a multiple vitamin (400 micrograms of folate) in addition to her
      diet (230 micrograms of folate), she would not exceed 1000 micrograms (1 mg)
      daily, which is considered the upper limit of daily folate ingestion by dietary
      fortification and supplementation before the masking of vitamin B12 becomes a
      concern. However, in this group of patients, pernicious anemia is rare. Regarding
      cardiovascular disease in men and women, there are no long-term studies showing
      the benefit of folic acid in reducing the homocysteine level. At present, there
      are only estimations. However, they should not be ignored. Although it is not the
      current standard of practice, adding a multiple vitamin containing folic acid to
      the regimen of men and women starting anticonvulsant medication should be
      considered in order to prevent the folate lowering observed with such commonly
      used drugs as PHT and carbamazepine. Women in childbearing years should be on a
      folic acid supplement when taking an anticonvulsant drug. In general, it appears
      that all men and women would benefit from increased folate intake. This can be
      accomplished through vitamin supplementation when there is compliance. However,
      if the food fortification for folate is increased in the future, then the issue
      of vitamin supplementation will have to be readdressed.

PMID- 11252850
TI  - Gender-specific approaches to mental health policy.

PMID- 11252851
TI  - Stroke and gender.
AB  - The literature regarding gender-specific aspects of cerebrovascular diseases is
      quite sparse. It is well-documented that the incidence of stroke is higher in men
      than in women in all age classes, and women are, on average, several years older
      than men when they suffer their first stroke. The prevalence of stroke is higher
      among men up to the age of approximately 80 years, after which it becomes higher
      in women. A majority of studies indicate that the case-fatality rate is higher in
      female than in male stroke patients; there is also some evidence, albeit
      relatively weak, indicating a better functional outcome in men. Gender
      differences in risk factor profile and treatment response appear to be weak. The
      burden of providing informal care to stroke patients seems to constitute a threat
      to the mental health of the caregivers, who are predominantly women.

PMID- 11252852
TI  - Gender differences and self-esteem.
AB  - The onset of adolescence--the period of transition between childhood and
      adulthood--is usually accompanied by dramatic and often difficult changes in the
      life of a young person. Biological, cognitive, social, and environmental factors
      all contribute to influence an adolescent's personal development and self-esteem.
      Studies have shown that adolescent girls tend to have lower self-esteem and more
      negative assessments of their physical characteristics and intellectual abilities
      than boys have. These findings may explain why the incidence of suicide attempts,
      depression, and eating disorders is substantially higher in girls. Future
      research on methods for promoting self-esteem may help reduce the negative
      feelings of adolescent girls, as well as the problems that stem from them.

PMID- 11252853
TI  - Medical management of premenstrual dysphoric disorder.
AB  - Women who suffer from severe dysphoric premenstrual complaints can now be
      accurately diagnosed. A diagnosis of premenstrual dysphoric disorder is best made
      by ruling out other psychiatric and general medical conditions and by collecting
      daily ratings of symptom expression across the menstrual cycle. Recent treatment
      findings support the use of (1) antidepressants that block the serotonin
      transporter, and (2) the benzodiazepine anxiolytic alprazolam. Medication
      administered only during the luteal phase of the cycle will result in substantial
      relief for patients suffering from severe premenstrual dysphoric disorder.

PMID- 11252854
TI  - Cognition and behavior in patients with Alzheimer's disease.
AB  - Clinically relevant differences in cognition and behavior exist between men and
      women with Alzheimer's disease. Underlying these differences are variations in
      the topographic brain changes caused by pathologic processes, as well as
      differences in hormonal brain physiology and genetic influences. Our
      understanding of how these gender differences affect the clinical expression of
      Alzheimer's disease is in its infancy. Research in this area will likely yield
      further insights into potential therapies directed toward symptomatic and
      preventive interventions.

PMID- 11252855
TI  - Gender-specific medicine--should it change the way we are doing business?

PMID- 11252856
TI  - Life after menopause.

PMID- 11252857
TI  - Domestic violence: a significant health problem.

PMID- 11252858
TI  - Drugs and smoking.
AB  - Generally, one should keep in mind that if a smoker takes a drug that is
      metabolized primarily by the CYP 1A2 system, an increased dose may be required.
      The patient should be closely monitored if he or she is taking several
      medications that may inhibit or induce the CYP 1A2 isoenzyme. Hepatic enzyme
      metabolism does not completely explain the effects of smoking on drugs, however,
      because smokers may have different physiologic responses to pain and sedation
      that depend on changes in plasma protein binding and in the rate and efficacy of
      subcutaneous absorption. Most of the few sex/gender-analyzed pharmacokinetic
      studies in smokers occurred after 1995. It appears that the 1993 changes at the
      National Institutes of Health and the Food and Drug Administration regarding
      inclusion of women in clinical trials enabled these examinations to take place.
      Because smokers--who make up nearly a quarter of the U.S. adult population--tend
      to consume more medications than nonsmokers, this social habit should be
      considered one of the most important to impact on drug metabolism in both sexes.

PMID- 11252859
TI  - No boys allowed?

PMID- 11252860
TI  - Gender differences in the etiology of anxiety sensitivity: a twin study.
AB  - OBJECTIVE: To estimate the magnitude of genetic and environmental factors on
      anxiety sensitivity by gender. DESIGN: Classic twins reared-together study
      design. PATIENTS: A community sample of 337 twin pairs, including 179 monozygotic
      (45 brother and 134 sister pairs) and 158 dizygotic (28 brother, 94 sister, and
      36 brother-sister pairs). METHOD: Twin pairs completed the Anxiety Sensitivity
      Index (ASI) using a postal survey design. The ASI is composed of three factors:
      (1) fear of anxiety-related somatic sensations; (2) fear of cognitive dyscontrol
      due to beliefs that sensations like depersonalization are signs of mental illness
      (e.g., fear of concentration problems); and (3) fear of publicly observable
      anxiety reactions (e.g., fear of trembling). Biometrical modeling techniques were
      used to estimate heritability of the ASI dimensions by gender. RESULTS: ASI
      factors are heritable only in women, accounting for 37% to 48% of the total
      variance (median, 44.5%). Environmental factors accounted for all the variability
      in men. CONCLUSIONS: These findings have implications for understanding the
      etiology of panic disorder. Previous research suggests that anxiety sensitivity
      is a risk factor or diathesis for this disorder, and that panic disorder is more
      prevalent in women than men. Our findings suggest the hypothesis that the
      increased prevalence in women may occur because anxiety sensitivity is heritable
      in women.

PMID- 11252861
TI  - The gender gap in cystic fibrosis survival.
AB  - Females with cystic fibrosis have significantly higher mortality than males from
      age 1 to age 20, resulting in an approximate four-year difference in median
      survival age. Survival is associated with a lack of colonization by pathogenic
      bacteria, as well as better pulmonary function, weight for height, and fitness.
      This statistically significant gender gap has been observed for decades and,
      therefore, is not likely to be the result of differential response to one of the
      newer treatments for cystic fibrosis.

PMID- 11252862
TI  - Sexual dysfunction secondary to depressive disorders.
AB  - Human sexuality has received less systematic study and is less well understood
      than other aspects of mental and physical health. Although depression itself,
      apart from medication, is generally believed to be associated with sexual
      dysfunction, the few existing studies report wide discrepancies with regard to
      frequency, gender, and quality of sexual dysfunction. Loss of libido is
      frequently and consistently associated with major depression. Moreover, sexual
      dysfunction secondary to depression or other factors is often mistaken for that
      caused by antidepressant medication. Although antidepressants have long been
      associated with sexual dysfunction, the precise nature and magnitude of sexual
      side effects have not been fully appreciated. This article will review the
      literature on sexual dysfunction associated with unmedicated depression and offer
      a guide for the clinician evaluating and treating depressed patients with sexual
      problems.

PMID- 11252864
TI  - Premenopausal or postmenopausal: what else is there?

PMID- 11252863
TI  - Dietary treatments for obesity.
AB  - Approximately 97 million Americans are classified as overweight or obese. Obesity
      alone is associated with an increased risk of early mortality and is an
      independent predictor of coronary heart disease (CHD) and its risk factors. The
      author reports that the biological, psychological, and sociological differences
      between men and women contribute to the varying success of dietary obesity
      treatments. She concludes that there is a demonstrated need for additional
      studies regarding the effects of gender on body weight, body composition, body
      fat distribution, and CHD risk factor responses to dietary weight loss
      interventions.

PMID- 11252865
TI  - Heart disease in women finally receives deserved Congressional attention.

PMID- 11252866
TI  - Drugs, vitamins, and gender.

PMID- 11252867
TI  - Death does us part.

PMID- 11252868
TI  - Estrogen, progesterone, and mood.
AB  - This article provides an overview of the literature on the role of estrogen and
      progesterone in modulating mood in women. The evidence that severe PMS is
      causally related to an ovarian hormone disorder is assessed. The influence of
      endogenous levels of estrogen and progesterone and of exogenously administered
      ovarian hormones on mood is evaluated.

PMID- 11252869
TI  - Cardiovascular disease and arrhythmias: unique risks in women.
AB  - Women have higher risks for symptomatic arrhythmias and sudden death than men. A
      significantly higher resting heart rate and longer QT interval on
      electrocardiogram may be factors that predispose women to a serious form of
      ventricular arrhythmia known as torsades de pointes. Recent studies have
      demonstrated hormonal effects on the expression of cardiac potassium and calcium
      ion channels, indicating their possible regulatory role in the modulation of
      cardiac repolarization and QT interval. These results demonstrate a need for
      greater awareness and further research into the mechanistic differences between
      men and women with respect to arrhythmia and cardiovascular disease.

PMID- 11252870
TI  - Gender-related aspects of eating disorders: a guide to practice.
AB  - Eating disorders have significantly different rates of incidence in males and
      females. Although there is ample scientific evidence supporting gender-specific
      diagnostic criteria, common stereotypes prevent accurate diagnosis of eating
      disorders in males. This article focuses on areas of practical consequence to
      physicians and other health professionals, emphasizing topics for which evidence
      based studies can direct treatment guidelines for both female and male patients.

PMID- 11252872
TI  - Use of niacin in the prevention and management of hyperlipidemia.
AB  - Niacin is an inexpensive drug useful in treating various forms of hyperlipidemia.
      Cardiac doses of niacin are effective in lowering serum triglyceride, low density
      lipoprotein, and lipoprotein-a levels and in elevating high density lipoprotein
      levels. Adverse reactions to niacin are varied and dose-dependent and range from
      annoying cutaneous flushing to hepatic toxicity. Patients advised to use the drug
      should be carefully screened and monitored. This paper reviews the pathologic and
      pharmacologic basis for niacin as an antilipemic agent. The biochemical and
      physiologic effects of the drug and its mechanisms of action are discussed.
      Emphasis is placed on the importance of aggressive management of serum lipids and
      the therapeutic uses of niacin. The use of niacin in primary and secondary
      prevention of heart disease is stressed. A patient education guide is included.

PMID- 11252871
TI  - Probable Alzheimer's disease: gender-related issues.
AB  - Probable Alzheimer's disease is diagnosed by exclusion when no other disorder-
      such as stroke, brain infection, or vitamin deficiency--can be found to account
      for specific cognitive change. Although probable Alzheimer's disease affects both
      men and women, studies in many different populations show that between 1.5 and 3
      times as many women as men suffer from probable Alzheimer's disease. For women
      with the disease, one needs to consider behavioral and cognitive problems,
      therapeutic issues, and other gender-related risks. Additionally, social,
      psychological, and emotional variables play a role in the female caregiver's
      burden.

PMID- 11252873
TI  - Advance practice nursing in heart transplantation.
AB  - This article describes the role of the advanced practice nurse in the field of
      cardiac transplantation. A brief review of the history of cardiac transplantation
      is presented. The role of advanced practice nursing is evolving and changing to
      meet patients' needs in an increasingly complex health care environment. The
      advanced practice nurse is uniquely qualified to meet those needs in a variety of
      roles and settings. The advanced practice nurse maybe a clinical nurse
      specialist, nurse practitioner, nurse mid-wife, or nurse anesthetist. Each role
      must include the element of clinical practice in order to be considered advanced
      practice nurse described in this article. The advanced practice nurse was a
      clinical nurse specialist in the role of cardiac transplant coordinator. This
      role comprises the sub-roles of educator, clinician, consultant, researcher, and
      administrator. The responsibilities and challenges of each sub-role are
      discussed. Suggestions for the direction of future practice are also presented.

PMID- 11252874
TI  - Teaching colleagues and the general public about automatic external
      defibrillators.
AB  - Every year 250,000 or more people with cardiovascular disease die within an hour
      of symptom onset and before they arrive at a hospital. With appropriate early
      defibrillation and follow-up treatment many people who might have died can now
      live. Nurses are key health care professionals for using automatic external
      defibrillators in hospitals and for teaching other first responders--inside and
      outside hospitals--how to use automatic external defibrillators. Features of
      automatic and semiautomatic external defibrillators are reviewed as well as
      ethical considerations for the use of automatic external defibrillators.

PMID- 11252876
TI  - Development of a nurse practitioner role in heart failure management: an
      Australian experience.
AB  - This paper describes the history of nurse practitioners and outlines the
      Australian experience in developing and implementing such a role. The legislative
      process and changes in introducing a nurse practitioner role are noted, and a
      trial to develop a framework for the nurse practitioner role in acute care in
      South Australia is highlighted.

PMID- 11252877
TI  - Lead wire reversal during 12-lead EKG monitoring.

PMID- 11252875
TI  - Oxidative stress and the role of antioxidants in cardiovascular risk reduction.

PMID- 11252878
TI  - Gene-based medicine: the new frontier.

PMID- 11252879
TI  - Heart retransplantation: what is the right choice?

PMID- 11252880
TI  - Bridging the gap between information, technology, and cardiovascular nursing.

PMID- 11252881
TI  - The effects of music on cardiac patients on bed rest.
AB  - Hospitalizations that require invasive cardiac procedures or support with an
      intra-aortic balloon pump can be unsettling. This study was undertaken to measure
      the effect of a music intervention on physiologic and psychological responses of
      patients on bed rest due to procedural sheaths or an intra-aortic balloon pump. A
      randomized, two-group, pretest/post-test design was utilized to measure the
      effect of a 30-minute music intervention on heart rate, blood pressure,
      respiratory rate, skin temperature, pain perception, and mood states. One hundred
      forty subjects participated, 65 in the control group and 75 in the treatment
      group. There were no significant differences between the groups in demographic,
      clinical, or baseline variables, except for respiratory rate. After the music
      intervention, there were reductions in blood pressure, respiratory rate, and
      psychological distress, as measured by the Profile of Mood States (p < 0.05).
      Music appeared to affect selected physiologic responses and reduce psychological
      distress in patients on bed rest.

PMID- 11252882
TI  - Gemcitabine as single-agent therapy in the management of advanced breast cancer.
AB  - Many active cytotoxic agents exist for breast cancer therapy, and numerous
      combination chemotherapy regimens are derived from them. Creating these
      combinations is sometimes empirically motivated by non-overlapping toxicities or
      the expectation of non-cross resistance. Yet, there is usually no absolute
      division of these aspects among cytotoxic agents, and the median survival for
      patients with metastatic breast cancer has not been dramatically prolonged by
      this approach. When the outcome of treatment is palliation rather than cure, it
      becomes paramount to optimize the dynamic equilibrium between chemotherapy
      induced side effects and the benefits attributable to relief of cancer-related
      symptoms. To this end, several recent clinical trials have evaluated the novel
      nucleoside analog gemcitabine (Gemzar) as single-agent therapy for advanced
      breast cancer. This article reviews these trials.

PMID- 11252883
TI  - Treatment of advanced breast cancer with gemcitabine and vinorelbine.
AB  - Breast cancer is sensitive to several cytotoxic drugs. Combination cytotoxic
      regimens are associated with higher response rates and longer durations of
      response and, occasionally, survival, than are single-agent regimens. However,
      combination regimens of conventional agents have not changed the course of the
      disease. In the past decade, numerous newer cytotoxic agents have been developed.
      Gemcitabine (Gemzar) and vinorelbine (Navelbine) are two such newer agents that
      have demonstrated good antitumor activity and favorable toxicity profiles as
      single-agent therapy for advanced breast cancer. Because gemcitabine and
      vinorelbine have different mechanisms of antitumor activity and good therapeutic
      indices, they have been evaluated as a combination regimen for the treatment of
      advanced breast cancer. Data from phase II clinical trials suggest that the
      combination of gemcitabine and vinorelbine with or without granulocyte colony
      stimulating factor is effective first- or second-line therapy for advanced breast
      cancer and has a favorable safety profile. Further studies of the
      gemcitabine/vinorelbine combination regimen are warranted.

PMID- 11252884
TI  - Docetaxel/gemcitabine: salvage chemotherapy in anthracycline-pretreated patients
      with advanced breast cancer.
AB  - Docetaxel (Taxotere) and gemcitabine (Gemzar) are active agents against breast
      cancer. Several phase I studies evaluated different schedules of their
      combination and clearly demonstrated that docetaxel and gemcitabine can be safely
      combined in either an every 3-week schedule or in a weekly and biweekly schedule.
      The toxicity profiles of these combinations were mainly grade 3 and 4 neutropenia
      and asthenia. Phase I studies also suggested that the docetaxel/gemcitabine
      combinations are active regimens in pretreated patients with advanced breast
      cancer. Three phase II studies of patients previously treated with anthracycline
      based chemotherapy reported a mean objective response rate of 46% and a mean
      overall survival of 13.5 months. Two of these trials enrolled patients with
      anthracycline-resistant or anthracycline-refractory disease; the objective
      responses using docetaxel/gemcitabine combination were 36% to 55% and 54%,
      respectively. It is noteworthy that objective responses were also achieved with
      this regimen in some patients who progressed while receiving taxane-based, front
      line chemotherapy. These efficacy results were obtained with a mild toxicity
      profile. Adverse events were of short duration and easily manageable. Further
      studies are needed to evaluate this combination as front-line chemotherapy as
      well as second-line in well-defined subgroups of patients with advanced breast
      cancer. Furthermore, the combination should be compared with other more standard
      or investigational regimens.

PMID- 11252885
TI  - Gemcitabine and paclitaxel as salvage therapy in metastatic breast cancer.
AB  - In a phase II trial, 29 patients with anthracycline-pretreated or anthracycline
      resistant metastatic breast cancer in whom anthracycline-containing first- or
      second-line chemotherapy failed received combination paclitaxel
      (Taxol)/gemcitabine (Gemzar). The initial regimen of paclitaxel at 175 mg/m2 on
      day 1 and gemcitabine at 1,000 mg/m2 on days 1, 8, and 15 of a 28-day cycle was
      given to five patients for a total of 27 cycles. The regimen resulted in
      excessive thrombocytopenia and was subsequently changed to gemcitabine at the
      same dose on days 1 and 8 of a 21-day cycle, with study treatment being given for
      a maximum of eight cycles. This regimen was well tolerated. Further evaluation of
      this regimen in minimally and heavily pretreated patients with advanced breast
      cancer is warranted.

PMID- 11252887
TI  - Gemcitabine and Pemetrexed disodium in treating breast cancer.
AB  - Pemetrexed disodium (Alimta, LY231514) is a novel, multitargeted antifolate that
      inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide
      ribonucleotide formyl transferase. This agent is broadly active in a wide variety
      of solid tumors, including breast cancer. Pemetrexed disodium has also shown
      clinically relevant activity in combination with gemcitabine (Gemzar). This
      combination is being evaluated for the treatment of metastatic breast cancer.

PMID- 11252886
TI  - Gemcitabine plus cisplatin in breast cancer.
AB  - In recent years, the clinical application of paclitaxel (Taxol), docetaxel
      (Taxotere), vinorelbine (Navelbine), and trastuzumab (Herceptin) has improved the
      management of advanced breast cancer. With the introduction of gemcitabine, a new
      drug with significant activity in breast cancer has become available. As a single
      agent, gemcitabine (Gemzar) provides response rates in the range of 25% to 46% in
      breast cancer, depending on starting dose and status of prior chemotherapy for
      metastatic disease. Higher response rates are observed when gemcitabine is
      combined with other classes of cytotoxic drugs. Studies conducted in our
      laboratory detected high degrees of synergy between gemcitabine and cisplatin
      (Platinol) in a variety of human tumors in primary culture. These analyses
      identified breast cancer as a target for this combination. The combination of
      cisplatin plus gemcitabine is active in relapsed breast cancer patients. The
      activity observed in drug-resistant patients suggests relative non-cross
      resistance with other drug combinations.

PMID- 11252889
TI  - The gemcitabine/epirubicin/paclitaxel trials in advanced breast cancer.
AB  - Numerous trials have shown that the pharmacokinetic interferences of epirubicin
      (Ellence)/paclitaxel (Taxol) combinations produce less pharmacodynamic effect
      than doxorubicin/paclitaxel regimens. Paclitaxel is more easily combined when
      infused over 3 (as compared to 24) hours; the administration of optimal doses of
      both agents is important. Based on these findings, a phase II study was performed
      to evaluate the feasibility and activity of the combination of gemcitabine
      (Gemzar), epirubicin, and paclitaxel as first-line therapy in advanced breast
      cancer. Patients received gemcitabine at 1,000 mg/m2 on days 1 and 4, plus
      epirubicin at 90 mg/m2 on day 1, plus paclitaxel at 175 mg/m2/d on day 1 every 21
      days. After six courses, patients less than 60 years old and in complete or
      partial remission or stable disease were treated with high-dose chemotherapy as
      consolidation treatment. The overall response rate was 92%, with 31% complete
      responses; 25 patients received high-dose chemotherapy, achieving a final overall
      response rate of 97%, with 47% complete responses. At a median follow-up of 25
      months, median progression-free survival is 21 months. Grade 4 neutropenia was
      observed in 64% of patients. Other hematologic toxicities were mild. Mild to
      moderate peripheral neuropathy was experienced by 39% of patients; grade 2 or 3
      mucositis occurred in 25% and 17% of patients, respectively. Based on these
      results, a multicenter trial has been started in seven Italian centers to confirm
      the feasibility of this regimen.

PMID- 11252888
TI  - Gemcitabine, paclitaxel, and trastuzumab in metastatic breast cancer.
AB  - A phase II trial evaluated the effectiveness and toxicity of combination
      paclitaxel (Taxol), gemcitabine (Gemzar), and trastuzumab (Herceptin) as first
      line therapy for patients with newly diagnosed HER2-overexpressing metastatic
      breast cancer. To date, 27 patients have received paclitaxel at 175 mg/m2 over 3
      hours on day 1, plus gemcitabine at 1,200 mg/m2 on days 1 and 8, plus trastuzumab
      at a 4-mg/kg loading dose on day 1, followed by 2 mg/kg weekly. Treatment cycles
      were repeated every 21 days. Responding or stable patients who had received six
      cycles of combination therapy continued single-agent trastuzumab weekly until
      disease progression. Treatment was generally well tolerated with grade 4 toxicity
      limited to myelosuppression. In all, 12 patients have achieved a partial
      remission and 1 patient had progressive disease; 14 patients continue treatment
      and have not yet been evaluated for response. Combination treatment with
      paclitaxel, gemcitabine, and trastuzumab is well tolerated and appears to be
      highly active. Accrual will continue to a total enrollment of 46 patients.

PMID- 11252890
TI  - Biweekly gemcitabine, doxorubicin, and paclitaxel as first-line treatment in
      metastatic breast cancer. Final results from a phase II trial.
AB  - In a single-center, open, phase II trial, we assessed the toxicity and activity
      of a triple combination therapy--doxorubicin at 30 mg/m2 (day 1), paclitaxel
      (Taxol) at 135 mg/m2 (day 2), and gemcitabine (Gemzar) at 2,500 mg/m2 (day 2
      after paclitaxel)--administered biweekly in a 28-day cycle for six cycles. This
      was given as first-line treatment in 41 patients with metastatic breast cancer.
      Granulocyte colony-stimulating factor was used in 27 patients to permit
      maintenance of dose density. Hematologic toxicity was moderate. Nonhematologic
      adverse events were generally mild. The objective response rate was 82.9% (34/41)
      with 18 patients (43.9%) achieving complete response and 16 (38%) achieving
      partial response; progressive disease was observed in 4 patients (9.8%).
      Responses were observed at all metastatic sites, including complete responses in
      lung, liver, bone, and soft tissue. Median duration of response was 14.1 months
      and median time to progression was 13.9 months. Median survival was 26.2 months.
      The biweekly combination of gemcitabine, doxorubicin, and paclitaxel is safe and
      highly active as first-line treatment in metastatic breast cancer.

PMID- 11252891
TI  - Recent advances in myocardial perfusion imaging.

PMID- 11252892
TI  - How cells read TGF-beta signals.
AB  - Cell proliferation, differentiation and death are controlled by a multitude of
      cell-cell signals, and loss of this control has devastating consequences.
      Prominent among these regulatory signals is the transforming growth factor-beta
      (TGF-beta) family of cytokines, which can trigger a bewildering diversity of
      responses, depending on the genetic makeup and environment of the target cell.
      What are the networks of cell-specific molecules that mould the TGF-beta response
      to each cell's needs?

PMID- 11252893
TI  - The many substrates and functions of ATM.
AB  - As its name suggests, the ATM--'ataxia-telangiectasia, mutated'--gene is
      responsible for the rare disorder ataxia-telangiectasia. Patients show various
      abnormalities, mainly in their responses to DNA damage, but also in other
      cellular processes. Although it is hard to understand how a single gene product
      is involved in so many physiological processes, a clear picture is starting to
      emerge.

PMID- 11252894
TI  - Three ways to make a vesicle.
AB  - Cargo molecules have to be included in carrier vesicles of different forms and
      sizes to be transported between organelles. During this process, a limited set of
      proteins, including the coat proteins COPI, COPII and clathrin, carries out a
      programmed set of sequential interactions that lead to the budding of vesicles. A
      general model to explain the formation of coated vesicles is starting to emerge
      but the picture is more complex than we had imagined.

PMID- 11252895
TI  - P63 and P73: P53 mimics, menaces and more.
AB  - Inactivation of the tumour suppressor p53 is the most common defect in cancer
      cells. The discovery of its two close relatives, p63 and p73, was therefore both
      provocative and confounding. Were these new genes tumour suppressors, p53
      regulators, or evolutionary spin-offs? Both oncogenic and tumour-suppressor
      properties have now been attributed to the p53 homologues, perhaps reflecting the
      complex, often contradictory, protein products encoded by these genes. p63 and
      p73 are further implicated in many p53-independent pathways, including stem-cell
      regeneration, neurogenesis and sensory processes.

PMID- 11252896
TI  - Are desmosomes more than tethers for intermediate filaments?
AB  - Desmosomes are intercellular adhesive junctions that anchor intermediate
      filaments at membrane-associated plaques in adjoining cells, thereby forming a
      three-dimensional supracellular scaffolding that provides tissues with mechanical
      strength. But desmosomes have also recently been recognized as sensors that
      respond to environmental and cellular cues by modulating their assembly state
      and, possibly, their signalling functions.

PMID- 11252897
TI  - Intramembrane proteolysis by presenilins.
AB  - Many neurodegenerative diseases involve the deposition of insoluble amyloid
      molecules. In Alzheimer's disease, for example, the amyloid beta-peptide (A beta)
      is the main component of the characteristic senile plaques. Proteolytic enzymes
      called secretases are involved in generating A beta, and one of these may have
      been identified as presenilin--a discovery that paves the way for a more complete
      understanding of presenilin structure and function.

PMID- 11252898
TI  - Krebs and his trinity of cycles.
AB  - Everyone who has ever taken biology at school has heard of the Krebs cycle, but
      few realize that Hans Krebs also discovered two other cycles. It is appropriate,
      at the centenary of his birth, to consider the circumstances and experiments that
      led Krebs to establish these metabolic pathways.

PMID- 11252899
TI  - The elusive cytostatic factor in the animal egg.
AB  - While animal eggs await fertilization, their cell cycle needs to be halted. The
      molecule responsible for this arrest--the cytostatic factor--was first described
      in 1971. But its identity was not revealed until 1989, and even now questions
      remain about this elusive factor.

PMID- 11252900
TI  - Human cancer cell lines: fact and fantasy.
AB  - Cancer cell lines are used in many biomedical research laboratories. Why, then,
      are they often described as unrepresentative of the cells from which they were
      derived? Here, I argue that they have been unjustly accused. Under the right
      conditions, and with appropriate controls, properly authenticated cancer cell
      lines retain the properties of the cancers of origin.

PMID- 11252901
TI  - [For rational use of antibiotics in the hospital].
AB  - Being faced with the risks of emergence and spread of antibiotic multiresistant
      bacterial strains in the hospital, it is a joint responsibility of all medical
      specialities and hospital management to promote the protection of the microbial
      ecology. Strategies to optimize antimicrobial use and practical approaches are
      discussed here. The need of mobilization of the entire hospital community and
      implementation of infectious diseases consultants is emphasized, as recommended
      by the "Groupement pour le Depistage, l'Etude et la Prevention des Infections
      Hospitalieres" (GDEPIH).

PMID- 11252902
TI  - [Diagnosis and treatment of gastroesophageal reflux in the adult: guidelines
      recommended by French and Belgian consensus].
AB  - Usual gastroesophageal reflux (GER) presentations are heartburn and acid
      regurgitation. The prevalence in occidental population ranges from 5 to 45%
      according to symptoms frequency. Oesophagitis is observed in 30 to 50% of
      examined patients and only erosive and ulcerative lesions must be considered.
      Distinction is made between non-severe oesophagitis (isolated loss of substance),
      severe oesophagitis (circonferential loss of substance) and complicated
      oesophagitis (stenosis, ulcerations, brachyoesophagus). 24-hour pH-monitoring
      analyses reflux duration and relations between symptoms and reflux specially in
      unusual extraoesophageal presentations. Symptoms and quality of life are the main
      criteria for staging. In few patients, oesophagitis is severe. Complications
      (stenosis, ulcerations, bleeding, endobrachyoesophagus) are observed in 10 to 15%
      of cases. Endobrachyoesophagus with intestinal metaplasia is a risk for
      neoplasia. The consensus conference proposes this initial therapeutic strategy.
      In cases of time-spaced symptoms: antiacids, alginic acid or low doses of anti-H2
      with life style changes. In cases of typical frequent symptoms, in patients
      younger than 50 years: 4-weeks treatment with half dosed proton pump inhibitors
      (PPI) or standard doses of anti-H2 or prokinetics. Nowadays, the majority of the
      experts propose empiric full-dose treatment. This attitude is more logical as
      total symptoms suppression with full dose PPI brings positive clues for exact GOR
      diagnostic without endoscopy. In patients older than 50 years or with alarming
      symptoms (weight loss, dysplagia, bleeding, anemia): endoscopy must be performed.
      Patients with non severe oesophagitis: PPI without checking endoscopy. In
      patients with severe or complicated oesophagitis: 8-weeks treatment following by
      endoscopy; in non relieved patients: doses are increased. In cases of
      extraoesophageal presentations: standard PPI treatment during 4 to 8 weeks if GER
      is well established. In long term strategy, if recidives are rare: intermittent
      treatment. In early and frequent recidives: long term adapted PPI or surgery.
      Stenosis are treated by PPI, pneumatic dilatation or surgery if unsuccessful.
      Brachyoesophagus must be checked by endoscopy every 2 years (malignancy risk).

PMID- 11252903
TI  - [Immunotherapy of the future: new immunosuppression strategies].

PMID- 11252904
TI  - [The European Directive 96/29/Euratom through the history of radiation
      protection].
AB  - The new european directive concerning the radiation protection 96/29/Euratom is
      currently being transposed in national regulations. This directive is registered
      in a historical context. This context allows us to understand how it is realised
      and what philosophy underlies the actual structure and its possible shortcomings.
      Current developments of the radiobiology and the radio-epidemiology, notably
      important modifications of our knowledge about natural irradiation, the attention
      for genetic fragile populations and relationships between irradiation and cancer
      are likely to modify our perception of the radiation protection.

PMID- 11252905
TI  - [Anticholinesterases in Alzheimer's disease].
AB  - During the last years, treatment of Alzheimer's disease has improved following a
      better detection of this disease and, more importantly, following a better
      knowledge of its physiopathogeny. After years of aspecific symptomatic
      treatments, acetylcholinesterase inhibitors have been recently released and can
      be considered as a specific symptomatic treatment. In this pharmacologic class,
      more practical and less toxic drugs are nowadays available. Treatments of
      behavioral disturbances have also been recently improved. Nowadays we have to
      find treatments able to modify the clinical evolution and eventually prognosis of
      this disease, and even to prevent it for the patients at risk. Nevertheless a
      simplification of the prescriptions is justified, to the detriment of drugs
      without any proven activity.

PMID- 11252906
TI  - [AL amyloidosis].
AB  - AL amyloidosis is a systemic disease caused by the deposition of fibrillar
      proteins in organs and tissues. These deposits are responsible for organic
      dysfunctions and may be rapidly lethal. Current therapy is unsatisfactory. We
      describe three clinical cases of multisystemic AL amyloidosis but with different
      initial presentation: nephrotic syndrome, cardiac failure and hepatic
      insufficiency. We review the literature about the clinical features, diagnostic
      methods and treatment of the disease.

PMID- 11252907
TI  - [Surgical treatment aspects in osteo-articular infections in the adult].

PMID- 11252908
TI  - [Oncology congress on emergencies and severe cancer complications].

PMID- 11252909
TI  - [Albert Dalcq (1893-1973)].

PMID- 11252910
TI  - Improving treatment for patients who are elderly and have dementia.

PMID- 11252911
TI  - Ethical challenges posed by dementia and driving.

PMID- 11252912
TI  - Sexuality and intimacy in the nursing home: a romantic couple of mixed cognitive
      capacities.

PMID- 11252913
TI  - Commentary on "Sexuality and intimacy in the nursing home".

PMID- 11252914
TI  - The myth of home and the medicalization of the care of the elderly.

PMID- 11252915
TI  - Physicians' responses to clinical scenarios involving life-threatening illness
      vary by patients' age.

PMID- 11252916
TI  - Commentary: medical decision making based on chronological age--cause for
      concern.

PMID- 11252917
TI  - Actual and perceived stability of preferences for life-sustaining treatment.

PMID- 11252918
TI  - Are non-heart-beating cadaver donors acceptable to the public?

PMID- 11252919
TI  - Can assisted suicide be regulated?

PMID- 11252920
TI  - Narrative unity and the unraveling of personal identity: dialysis, dementia,
      stroke, and advance directives.

PMID- 11252922
TI  - Gender and the heart: sex-specific differences in normal anatomy and physiology.
AB  - Important sex-specific differences in the normal anatomy and physiology of the
      myocardium exist. It is essential to consider these differences in assessing the
      meaning of cardiac symptoms in men and women and in constructing strategies for
      the prevention and treatment of cardiovascular illness.

PMID- 11252921
TI  - Legal trends in bioethics.

PMID- 11252923
TI  - Gender and the immune system.

PMID- 11252924
TI  - Gender-specific medicine and dermatology: clinical implications.

PMID- 11252925
TI  - The mysterious effect of reproductive hormones on cognitive function: scientific
      knowledge in search of an application.

PMID- 11252927
TI  - Depression and gender: implications for primary care.

PMID- 11252926
TI  - Gender-based biology and the gastrointestinal tract.

PMID- 11252928
TI  - Gender differences in musculoskeletal health.

PMID- 11252929
TI  - Gender specificity and osteoporosis.
AB  - To a certain extent, the emphasis placed on women in light of the predominance of
      osteoporosis in this sex is well-justified. As researchers are appreciating the
      potential size of the male population at risk for osteoporosis, increasing
      interest is becoming apparent on the part of investigators and the pharmaceutical
      companies that are developing therapies. As more is learned about osteoporosis in
      men, experts will then be in a position to better understand the similarities and
      differences between genders.

PMID- 11252930
TI  - Immunotherapy for non-Hodgkin's lymphoma.
AB  - The first attempt at using monoclonal antibodies in lymphoma therapy, reported in
      1980, was unsuccessful. Since that time, several immunotherapeutic approaches to
      treating non-Hodgkin's lymphoma have been developed, with varying degrees of
      success. These approaches are largely based on the fact that each lymphoma is a
      clone of identical cells with a unique immunoglobulin on its surface. This unique
      portion of the immunoglobulin--the idiotype--is an ideal target for therapy.
      Clinical trials with antibodies have mostly targeted CD20, which is present on
      95% of all B-cell lymphomas, as well as CD19 and CD22. This concept of using the
      idiotype to broaden the antilymphoma effect and to use it as a vaccine model has
      recently been evaluated. This approach would theoretically produce an active
      immunization with induction of humoral and cellular responses that would be
      longer acting than passive antibodies alone. The response is heterogeneous and
      polyclonal, which may be an advantage. Studies of these approaches will be
      outlined in this article.

PMID- 11252931
TI  - Painful osteoblastic metastases: the role of nuclear medicine.
AB  - Although bone pain from osteoblastic metastases can be ameliorated 50% to 80% of
      the time by use of intravenously or orally administered radiopharmaceuticals, we
      cannot accurately predict who will or will not respond. The radiopharmaceuticals
      containing phosphorus-32, strontium-89 (Metastron), rhenium-186, samarium-153
      lexidronam (Quadramet), and tin-117m are effective, but we do not know which of
      these is the most efficacious or the safest. Toxicity includes mild-to-moderate
      pancytopenia and an occasional brief flare of pain, and treatment of patients
      with disseminated intravascular coagulation must be avoided because it may
      predispose the patient to severe thrombocytopenia. Treatment may be repeated at
      approximately 8- to 12-week intervals, depending on the time of return to normal
      leukocytes and platelet counts. Tumoricidal effects are probably not the sole
      mechanism of pain relief.

PMID- 11252932
TI  - Clinical trials referral resource. Current cooperative group phase III clinical
      trials in early-stage breast cancer.

PMID- 11252933
TI  - Brachytherapy in the treatment of breast cancer.
AB  - Whole-breast external-beam radiation therapy (EBRT) involves a 6-week course of
      fractionated treatments. In contrast, brachytherapy can be completed in a 4- to 5
      day treatment course. Because of this shortened time frame, there has been
      interest in breast brachytherapy as a sole modality after lumpectomy. The
      American Brachytherapy Society (ABS) has issued guidelines specifically for the
      use of brachytherapy in breast carcinoma. In these guidelines, the ABS addresses
      important areas of controversy related to the indications, execution, and
      evaluation of breast implants when utilized in the following settings: as the
      sole treatment modality following lumpectomy, as an alternative to a 6-week
      course of EBRT following lumpectomy, as a boost following whole-breast
      irradiation, and for the treatment of local recurrences following breast
      conservation treatment. The ABS recommends a precise definition and meticulous
      delineation of the clinical target volume. In addition, the Society recommends
      the routine use of dose-volume histograms and a dose-homogeneity index as tools
      to ensure reproducible brachytherapy and to allow interinstitutional comparisons.
      Brachytherapy as a sole modality is currently considered investigational and
      should be performed in the context of a controlled clinical trial. Practitioners
      and cooperative groups are encouraged to use these guidelines to formulate
      treatment and dose-reporting policies, but responsibility for medical decisions
      ultimately rests with the treating radiation oncologist.

PMID- 11252934
TI  - Current status and optimal use of radiosurgery.
AB  - The field of stereotactic radiosurgery is rapidly advancing as a result of both
      improvements in radiosurgical equipment and better physician understanding of the
      clinical applications of stereotactic radiosurgery. This article will review
      recent developments in the field of radiosurgery, including advances in our
      understanding of the treatment of brain metastases and arteriovenous
      malformations, as well as the use of stereotactic radiosurgery as a boost
      following conventional radiation for nasopharyngeal carcinoma to minimize the
      rate of local recurrence. In addition, improved understanding of the radiobiology
      of normal neurologic structures adjacent to tumors undergoing radiosurgery has
      led to the use of fractionated stereotactic radiosurgery for the treatment of
      acoustic neuromas and tumors bordering the anterior visual pathways. Finally, a
      breakthrough in radiosurgery involving the development and use of frameless,
      image-guided stereotactic radiosurgery has allowed for both dose homogeneity and
      treatment of intracranial lesions based on nonisocentric treatment algorithms
      that result in improved target conformality. This same frameless radiosurgical
      system has also expanded the scope of radiosurgery to include the treatment of
      extracranial lesions throughout the body.

PMID- 11252935
TI  - Corticosteroids in advanced cancer.
AB  - Despite the fact that there are only a few controlled trials demonstrating the
      benefits associated with the use of corticosteroids in specific situations, these
      agents are administered frequently to patients with advanced cancer.
      Corticosteroids may be used alone or as adjuvants in combination with other
      palliative or antineoplastic treatments. For example, corticosteroids may help
      prevent nausea, vomiting, and hypersensitivity reactions to treatment with
      chemotherapy or radiation. They are also commonly used as appetite stimulants in
      patients with advanced cancer. In the adjuvant setting, corticosteroids help to
      alleviate pain in advanced cancer patients, including specific situations such as
      back pain related to epidural compression. This article reviews the evidence
      supporting the use of corticosteroids in a broad range of situations seen in
      patients with advanced cancer.

PMID- 11252936
TI  - [Laennec and music].

PMID- 11252937
TI  - [Physiology and pharmacology of lacrymal and salivary secretions].
AB  - Salivary and lacrymal glands have secretory mechanisms similar to those of other
      exocrine glands. Saliva results from two different but integrated processes i.e.
      hydroelectrolytic transport and protein secretion by regulated exocytosis. Both
      cellular processes are regulated by the autonomic nervous system with
      complementary effects without antagonism, and parasympathetic innervation
      predominates. Signal transduction mechanisms in salivary cells include: increases
      in cytosolic calcium, cyclic AMP and cyclic GMP. The tear film consists of three
      layers: mucous inner layer, middle aqueous layer, and outer lipid layer. Each
      layer secretion is strongly regulated. Aqueous layer secretion is controlled by
      autonomic nervous system and signal transduction depends from cyclic AMP and
      intracellular calcium levels. A review of drugs used in France modulating
      lacrymal and salivary secretions is proposed.

PMID- 11252938
TI  - [Dry eye].
AB  - As the term of "dry eye" is very common among people and physicians, the presumed
      definition of this entity is rather wrong. The simplistic triple equation: "dry
      eye = Sjogren's syndrome = artificial tears" belongs definitively to the past.
      This review is an attempt to demonstrate the complexity of the tear film
      regulation, the difficulties of an accurate diagnosis and finally the numerous
      therapeutic attitudes we can held for each sicca syndrome.

PMID- 11252939
TI  - [Dry mouth].
AB  - The sensation of dry mouth is a common problem, often neglected. The decrease of
      salivary flow causes chronic oral discomfort and functional problems and
      predisposes to rampant dental caries and oral candidiasis. Various methods are
      described to evaluate salivary gland hypofunction but no single test has
      sufficiently high specificity and sensitivity. Categorised questionnaires and
      unstimulated whole saliva flow are valuable. The causes of xerostomia are
      numerous, of which the principal are, drug or radiation induced xerostomia and
      primary an secondary Sjogren's syndrome. Treatment calls for good hydration,
      optimal oral hygiene and prophylaxis of candidosis. All unnecessary medications
      must be avoided. Oral pilocarpine is the only drug which had demonstrated
      beneficial effects if no contraindications exist.

PMID- 11252940
TI  - [Vaginal dryness].
AB  - Vaginal dryness is one of the "little problems" that are too often, ignored. The
      disorder essentially manifests at the time of menopause, but can occur at other
      times, such as with oral contraception, following vaginal infection, after
      treatment for infection, etc. Screening for the disorder should become routine.
      Management should have precise objectives: cure of the infection and
      restablishment of the vaginal flora in order to reconstitute a natural balance.
      Treatment can be adapted for each patient to obtain effective and lasting
      results.

PMID- 11252941
TI  - [Primary Gougerot-Sjogren's syndrome].
AB  - Sjogren's syndrome is characterized by the association of a Sicca syndrome
      prevailing at the ocular and oral level and of extra-glandular involvement of
      immuno-inflammatory mechanism: nonerosive polyarthritis, Raynaud's phenomenon,
      cutaneous and (or) neurological vasculitis, pulmonary involvement and
      interstitial nephropathy. In the typical forms, the biological signs associate a
      polyclonal hypergammaglobulinemia, sometimes a cryoblogulinemia, rheumatoid
      factor and anti SSA and anti SSB ANA. The diagnosis is confirmed by minor
      salivary gland biopsy showing a lymphoid infiltrate in clusters. These biological
      anomalies, the presence of major salivary gland enlargements and extra-glandular
      manifestations, characterize the progressive forms of the disease with a high
      risk of evolution towards malignant lymphoma. Antimalarial drugs are used in the
      treatment of polyarthritis, corticosteroids and immunosuppressive agents in
      serious extra-glandular involvement.

PMID- 11252942
TI  - [Immunopathology of Gougerot-Sjogren syndrome].
AB  - Sjogren's syndrome presents as an autoimmune exocrinopathy, and the term
      autoimmune epitheliitis has recently been coined. The major lesion is a
      lymphocyte infiltrate affecting the salivary glands and consisting predominantly
      of activated CD4+ T cells. The remaining 20% B lymphocytes, first polyclonal,
      turn out to be monoclonal. Epithelial cells are endowed with a key-part in the
      play, inasmuch as they gather together most of the Sjogren's syndrome-specific
      target autoantigens within apoptotic bodies, and possess all the characteristics
      of antigen presenting cells. There appears to be every likelihood that the
      sequence is triggered off by a thus far unknown virus.

PMID- 11252943
TI  - [Secondary Gougerot-Sjogren syndrome].
AB  - Secondary Sjogren's syndrome is due to another disease. When it develops in
      connective tissue diseases, their causative role is unchallenged. In AIDS or
      hepatitis C, exocrine involvement is virus related. Whether or not it qualifies
      for Sjogren's syndrome is debated. Amyloidosis and sarcoidosis do not produce
      direct, autoimmune lesions of the glands, hence their exocrine involvements are
      considered as differential diagnoses. The most common Sjogren's syndrome is found
      in rheumatoid arthritis. When it appears, the arthritis has been evolving for
      years, and has reached its typical, seropositive and erosive stage. Accordingly,
      dryness is not a major concern and should be sought for by proper questioning,
      specially on eye dryness. When a secondary Sjogren's syndrome is an early
      complication of rheumatoid arthritis, it could be confused with a primary
      syndrome with prominent joint involvement. In systemic lupus erythematosus,
      secondary Sjogren's syndrome develops rarely in the first years of evolution but
      later in life, when the patient becomes menopausal. In systemic sclerosis,
      especially in CREST, secondary syndrome can lead to the discovery of the
      unsuspected connective tissue disease thanks to mouth dryness. It can reveal
      primary biliary cirrhosis or auto-immune hepatitis. Often precede a true primary
      Sjogren dysfunctions of the thyroid.

PMID- 11252944
TI  - [Sicca syndromes in the elderly].
AB  - Sicca syndromes, especially salivary sicca syndromes, are prevalent in the
      elderly. Even, in the absence of local complications, they can impair the quality
      of life and lead to denutrition. Drugs are essentially responsible for these
      sicca syndromes. Paraclinic investigations (tests for autoimmunity, biopsy of
      minor salivary glands) are useful when uncommon Sjogren syndrome is hypothesized.
      This autoimmune disease, probably rare in the elderly, has to be suspected when
      general manifestations are present. The treatment of sicca syndromes is based on
      the reduction of drug prescriptions and on local care.

PMID- 11252945
TI  - [The prescriber and the pedagogue].

PMID- 11252946
TI  - [Thyroid cancers. Pathology, diagnosis].

PMID- 11252947
TI  - [Humoral immunity. B lymphocytes; immunoglobulins (structure, diversity,
      function); clinical practice investigations; concept of humoral immunity
      deficiency].

PMID- 11252948
TI  - [Bacterial endocarditis. Etiology, physiopathology, diagnosis, evolution,
      treatment].

PMID- 11252949
TI  - [Iron-deficiency anemia. Etiology, physiopathology, diagnosis, treatment with
      iron administration].

PMID- 11252950
TI  - [Agitated state. Diagnosis orientation and management in an emergency situation,
      with drug administration].

PMID- 11252951
TI  - [Bacterial skin infections: impetigo, furuncle, erysipelas. Etiology, diagnosis,
      evolution, treatment].

PMID- 11252952
TI  - Rab proteins as membrane organizers.
AB  - Cellular organelles in the exocytic and endocytic pathways have a distinctive
      spatial distribution and communicate through an elaborate system of vesiculo
      tubular transport. Rab proteins and their effectors coordinate consecutive stages
      of transport, such as vesicle formation, vesicle and organelle motility, and
      tethering of vesicles to their target compartment. These molecules are highly
      compartmentalized in organelle membranes, making them excellent candidates for
      determining transport specificity and organelle identity.

PMID- 11252953
TI  - Prions: health scare and biological challenge.
AB  - Although human prion diseases are rare, the incidence of 'new variant'
      Creutzfeldt-Jakob disease in the United Kingdom is increasing exponentially.
      Given that this disease is probably the result of infection with bovine prions,
      understanding how prions replicate--and how to counteract their action--has
      become a central issue for public health. What are the links between the bovine
      and human prion diseases, and how do prions reach and damage the central nervous
      system?

PMID- 11252954
TI  - Untangling the ErbB signalling network.
AB  - When epidermal growth factor and its relatives bind the ErbB family of receptors,
      they trigger a rich network of signalling pathways, culminating in responses
      ranging from cell division to death, motility to adhesion. The network is often
      dysregulated in cancer and lends credence to the mantra that molecular
      understanding yields clinical benefit: over 25,000 women with breast cancer have
      now been treated with trastuzumab (Herceptin), a recombinant antibody designed to
      block the receptor ErbB2. Likewise, small-molecule enzyme inhibitors and
      monoclonal antibodies to ErbB1 are in advanced phases of clinical testing. What
      can this pathway teach us about translating basic science into clinical use?

PMID- 11252955
TI  - Filamins as integrators of cell mechanics and signalling.
AB  - Filamins are large actin-binding proteins that stabilize delicate three
      dimensional actin webs and link them to cellular membranes. They integrate
      cellular architectural and signalling functions and are essential for fetal
      development and cell locomotion. Here, we describe the history, structure and
      function of this group of proteins.

PMID- 11252956
TI  - Confounded cytosine! Tinkering and the evolution of DNA.
AB  - Early in the history of DNA, thymine replaced uracil, thus solving a short-term
      problem for storing genetic information--mutation of cytosine to uracil through
      deamination. Any engineer would have replaced cytosine, but evolution is a
      tinkerer not an engineer. By keeping cytosine and replacing uracil the problem
      was never eliminated, returning once again with the advent of DNA methylation.

PMID- 11252957
TI  - Retroviral recombination: what drives the switch?
AB  - The high rate of recombination in retroviruses is due to the frequent template
      switching that occurs during reverse transcription. Although the mechanism that
      leads to this switch is still a matter of debate, there is increasing evidence
      that specific RNA structures are involved. And the implications might go beyond
      retroviral genetic variability.

PMID- 11252958
TI  - Licence to kill.

PMID- 11252960
TI  - Eating well.

PMID- 11252959
TI  - Unpicking NPC.

PMID- 11252961
TI  - Take steroids to move faster.

PMID- 11252962
TI  - Protein trafficking. Made for export.

PMID- 11252963
TI  - Ironing out a yellow stripe.

PMID- 11252964
TI  - On track with kinesin.

PMID- 11252965
TI  - Pore performance.

PMID- 11252966
TI  - Motif with a motive.

PMID- 11252967
TI  - How Drosophila appendages develop.
AB  - Just a glance at the body of the fruit fly Drosophila reveals that it has a main
      body part--the trunk--and a number of specialized appendages such as legs, wings,
      halteres and antennae. How do Drosophila appendages develop, what gives each
      appendage its unique identity, and what can the fruit fly teach us about
      appendage development in vertebrates?

PMID- 11252968
TI  - SNARE-mediated membrane fusion.
AB  - SNARE proteins have been proposed to mediate all intracellular membrane fusion
      events. There are over 30 SNARE family members in mammalian cells and each is
      found in a distinct subcellular compartment. It is likely that SNAREs encode
      aspects of membrane transport specificity but the mechanism by which this
      specificity is achieved remains controversial. Functional studies have provided
      exciting insights into how SNARE proteins interact with each other to generate
      the driving force needed to fuse lipid bilayers.

PMID- 11252969
TI  - [Anti-infection prophylaxis after sexual assault. Experience of the Raymond
      Poincare-Garches Hospital].
AB  - OBJECTIVE: The August 1997 Directive of the Direction of General Health in France
      extended indications for antiretroviral treatment to risk of HIV exposure by
      sexual intercourse or syringe sharing. In November 1997, in collaboration with
      the Hauts-de-Seine MedicoJudiciary center, the Infectious Disease unit of the
      Raymond Poincare Garches Hospital established a health care and anti-HIV
      prophylaxis clinic for victims of sexual assault. We report here the experience
      in 1998 and 1999. PATIENTS AND METHODS: Between January 1998 and December 1999,
      109 victims of sexual assault, 105 women and 4 men, mean age 24.7 +/- 10.6 years
      attended the clinic. RESULTS: Mean delay from assault to antiretroviral
      tritherapy (AZT, 3TC, indinavir) was 18.35 +/- 17.39 hours. Mean duration of
      antiretroviral treatment was 17.4 +/- 11.8 days. HIV screening in perpetrators
      enabled early interruption of the antiretroviral treatment in 23 cases (21.1%).
      Sixty-two victims (62%) were still in follow-up at W4/W7. Excellent compliance to
      tritherapy was observed in these subjects. Clinical intolerance was observed in
      46.6% with nausea-vomiting in 91.4% of the cases. Adverse effects led to
      interruption of indinavir in 5 cases. Initial HIV serology was negative in all
      cases and no case of HIV seroconversion was observed. Among the 23 known
      perpetrators, one was HIV-positive with an HIV-RNA at 88,000 copies. Sixty-one
      victims (55.9%) had been previously vaccinated against the hepatitis B virus; 16
      victims were vaccinated after the assault. There were no cases of hepatitis B
      virus seroconversion. Search for chlamydiae in vaginal secretions was positive in
      3 cases and chlamydia serology demonstrated a seroconversion in 1 case. There was
      no case of syphylitic seroconversion and no case of gonococcal or trichomonas
      infection. CONCLUSION: The low rate of attendance for follow-up in regards to the
      gravity of the potential risk of HIV and/or hepatitis B virus transmission and
      the burden and cost of the antiretroviral treatment highlight the need for better
      medico-psycho-social support for rape victims. For the victims who attended the
      clinic, antiretroviral treatment was generally well accepted and well tolerated.